PMID- 24916042
TI  - Propionic acidemia in a previously healthy adolescent with acute onset of dilated
      cardiomyopathy.
AB  - Propionic acidemia (PA) is a rare autosomal recessive organic aciduria resulting
      from defects in propionyl-CoA-carboxylase (PCC), a key enzyme of intermediate
      energy metabolism. PA mostly manifests during the neonatal period, when affected
      newborns develop severe metabolic acidosis and hyperammonemia. We present a
      previously healthy teenager, who suffered from acute fatigue and breathlessness.
      The patient was tachycardic, displayed a precordial heave and a systolic murmur.
      Cardiac investigations revealed severe dilated cardiomyopathy (DCM). Biochemical
      work up led to the diagnosis of PA. Remarkably, this patient of consanguineous
      Hispanic origin was in a good general health condition before the acute onset of
      DCM. Diagnosis of PA was confirmed by enzymatic and molecular genetic analysis,
      the latter revealing a novel homozygous mutation in the PCCB gene (c.1229G > A;
      p.R410Q). Residual PCC enzyme activity of approximately 14 % of normal was
      detected in patient's lymphocytes and fibroblasts, thereby providing a possible
      explanation for the hitherto asymptomatic phenotype. CONCLUSION: Isolated DCM,
      although rare, can be the leading and/or sole symptom of late-onset PA.
      Therefore, patients with DCM should receive a comprehensive diagnostic evaluation
      including selective screening for inborn errors of metabolism.

PMID- 24916043
TI  - Carbon storage and potential methane production in the Hudson Bay Lowlands since
      mid-Holocene peat initiation.
AB  - Peatlands have influenced Holocene carbon (C) cycling by storing atmospheric C
      and releasing methane (CH4). Yet, our understanding of contributions from the
      world's second largest peatland, the Hudson Bay Lowlands (HBL), Canada, to peat
      climate-C-dynamics is constrained by the paucity of dated peat records and
      regional C-data. Here we examine HBL peatland development in relation to Holocene
      C-dynamics. We show that peat initiation in the HBL is tightly coupled with
      glacial isostatic adjustment (GIA) through most of the record, and occurred
      within suitable climatic conditions for peatland development. HBL peatlands
      initiated most intensively in the mid-Holocene, when GIA was most rapid and
      climate was cooler and drier. As the peat mass developed, we estimate that the
      HBL potentially released 1-7 Tg CH4 per year during the late Holocene. Our
      results indicate that the HBL currently stores a C-pool of ~30 Pg C and provide
      support for a peatland-derived CH4 contribution to the late Holocene atmosphere.

PMID- 24916044
TI  - Reciprocal interaction between the suprachiasmatic nucleus and the immune system
      tunes down the inflammatory response to lipopolysaccharide.
AB  - Several studies have shown circadian variations in the response of the immune
      system suggesting a role of the suprachiasmatic nucleus (SCN). Here we show that
      lipopolysaccharide (LPS) administration in the beginning of the active period
      induced more severe responses in temperature and cytokines than LPS given in the
      rest period. Moreover night administered LPS increased SCN basal neuronal
      activity indicating a direct influence of inflammation on the SCN. Bilateral
      lesions of the SCN resulted in an increased inflammatory response to LPS
      demonstrating that an interaction between the SCN and the immune system modulates
      the intensity of the inflammatory response.

PMID- 24916045
TI  - Aphid-encoded variability in susceptibility to a parasitoid.
AB  - BACKGROUND: Many animals exhibit variation in resistance to specific natural
      enemies. Such variation may be encoded in their genomes or derived from infection
      with protective symbionts. The pea aphid, Acyrthosiphon pisum, for example,
      exhibits tremendous variation in susceptibility to a common natural enemy, the
      parasitic wasp Aphidius ervi. Pea aphids are often infected with the heritable
      bacterial symbiont, Hamiltonella defensa, which confers partial to complete
      resistance against this parasitoid depending on bacterial strain and associated
      bacteriophages. That previous studies found that pea aphids without H. defensa
      (or other symbionts) were generally susceptible to parasitism, together with
      observations of a limited encapsulation response, suggested that pea aphids
      largely rely on infection with H. defensa for protection against parasitoids.
      However, the limited number of uninfected clones previously examined, and our
      recent report of two symbiont-free resistant clones, led us to explicitly examine
      aphid-encoded variability in resistance to parasitoids. RESULTS: After rigorous
      screening for known and unknown symbionts, and microsatellite genotyping to
      confirm clonal identity, we conducted parasitism assays using fifteen clonal pea
      aphid lines. We recovered significant variability in aphid-encoded resistance,
      with variation levels comparable to that contributed by H. defensa. Because
      resistance can be costly, we also measured aphid longevity and cumulative
      fecundity of the most and least resistant aphid lines under permissive
      conditions, but found no trade-offs between higher resistance and these fitness
      parameters. CONCLUSIONS: These results indicate that pea aphid resistance to A.
      ervi is more complex than previously appreciated, and that aphids employ multiple
      tactics to aid in their defense. While we did not detect a tradeoff, these may
      become apparent under stressful conditions or when resistant and susceptible
      aphids are in direct competition. Understanding sources and amounts of variation
      in resistance to natural enemies is necessary to understand the ecological and
      evolutionary dynamics of antagonistic interactions, such as the potential for
      coevolution, but also for the successful management of pest populations through
      biological control.

PMID- 24916046
TI  - Comments on: 'the infective endocarditis team: recommendations from an
      international working group'.

PMID- 24916047
TI  - Two (or more) sides of a coin.

PMID- 24916048
TI  - Decision to intervene in asymptomatic mitral regurgitation: 'more art than
      science'.

PMID- 24916049
TI  - Predominance of normal left ventricular geometry in the male 'athlete's heart'.
AB  - AIMS: This study evaluated (a) global LV adaption to endurance versus resistance
      training in male athletes, (b) LV assessment using by modern imaging technologies
      and (c) the impact of scaling for body size on LV structural data. METHODS: A
      prospective cross-sectional design assessed the LV in 18 elite endurance-trained
      (ET), 19 elite resistance-trained (RT) and 17 sedentary control (CT)
      participants. Standard 2D, tissue Doppler and speckle tracking echocardiography
      assessed LV structure and function. Indexing of LV structures to body surface
      area (BSA) was undertaken using ratio and allometric scaling. RESULTS: Absolute
      and scaled LV end-diastolic volume (ET: 43.7+/-6.8; RT: 34.2+/-7.4; CT 32.5+/-8.9
      mL/m(1.5); p<0.05) and LV mass (ET: 29.8+/-6.6; RT: 25.4+/-8.7; CT 25.9+/-6.4
      g/m(2.7); p < 0.05) were significantly higher in ET compared with RT and CT. LV
      wall thickness were not different between ET and RT. 65% of ET and 95% of RT had
      normal geometry. Stroke volume was higher in ET compared with both RT and CT
      (p<0.05). Whilst regional tissue velocity data were not different between groups,
      longitudinal and basal circumferential strain (epsilon) was reduced in RT
      compared with ET. CONCLUSIONS: In this comprehensive evaluation of the male
      athlete's heart (AH), normal LV geometry was predominant in both athlete groups.
      In the ET, 30% demonstrated an eccentric hypertrophy with no concentric
      hypertrophy in RT. Cardiac epsilon data in RT require further evaluation, and any
      interpretation of LV size should appropriately index for differences in body
      size.

PMID- 24916050
TI  - Aborted myocardial infarction in ST-elevation myocardial infarction: insights
      from the STrategic Reperfusion Early After Myocardial infarction trial.
AB  - BACKGROUND: We evaluated the prespecified endpoint, aborted myocardial infarction
      (AbMI), according to the use of a pharmacoinvasive (PI) strategy versus primary
      percutaneous coronary intervention (PCI) in 1754 patients randomised within 3 h
      of symptom onset in the STrategic Reperfusion Early After Myocardial infarction
      (STREAM) trial. METHODS: Based on sequential ECG's and biomarkers, AbMI was
      defined as ST-elevation resolution >=50% (90 min posttenecteplase (TNK) in the PI
      arm or 30 min postprimary PCI) with minimal biomarker rise. RESULTS: In the PI
      arm 11.1% (n=99) had AbMI versus 6.9% (n=59) in primary PCI arm (p<0.01). In a
      multivariable model, AbMI patients overall had less baseline SigmaST-deviation,
      fewer baseline Q-waves and shorter total ischaemic times. PI AbMI patients had
      faster time to TNK (90 vs 100 min, p=0.015): total ischaemic time was 100 min
      longer in primary PCI AbMI patients and no difference in ischaemic time existed
      between AbMI and non-AbMI patients within this group. Although no significant
      interaction between treatment and AbMI on the composite endpoint of
      death/shock/congestive heart failure/recurrent MI occurred (p=0.292), PI AbMI
      patients had a lower incidence in this endpoint than non-AbMI patients (5.1 vs
      12%, p=0.038); this was not evident in primary PCI patients. Forty-five patients
      (ie, 2.5%) had masquerading MI with minimal biomarker elevation and no evolution
      in baseline ST-elevation. CONCLUSIONS: A PI strategy of early fibrinolysis more
      frequently aborts MI than primary PCI. Such PI patients had more favourable
      outcomes as compared with non-AbMIs. Diligent review of ECG evolution in STEMI
      distinguishes AbMI from infarct masquerade. ClinicalTrials.gov ID: NCT00623623.

PMID- 24916051
TI  - Polyproline promotes tetramerization of recombinant human butyrylcholinesterase.
AB  - Human BChE (butyrylcholinesterase) protects against the toxicity of
      organophosphorus nerve agents and pesticides. BChE purified from human plasma is
      limited and pathogen carry-over is a concern. Unlike the native BChE tetrameric
      complex with a residence time of days, rBChE (recombinant BChE) is produced
      predominantly as dimers and monomers that are cleared from the circulation within
      minutes. Assembly into tetramers requires incorporation of proline-rich peptides,
      a process that was thought to occur intracellularly. Our goal was to determine
      whether polyproline added to rBChE under cell-free conditions would promote
      tetramerization. Secreted rBChE was purified by procainamide affinity
      chromatography, and synthetic polyprolines (8-mer to 300-mer) were tested to
      determine their effect on tetramer assembly. These studies demonstrated that 90
      98% of purified rBChE (65 MUM) could be assembled into tetramers when incubated
      with synthetic 17-mer or 50-mer polyproline peptides (100 MUM) for 1.5 h at 25
      degrees C. However, rBChE tetramerization was inefficient with smaller 8-mer
      polyproline peptides and larger 300-mer polyproline proteins. Collectively, these
      studies demonstrated that the eukaryotic cellular machinery is not required for
      assembly of active BChE into tetramers and that this process can occur in vitro
      with purified rBChE in the presence of peptides containing 15-50 consecutive
      proline residues. 

PMID- 24916052
TI  - Light-induced color changes of microgel-based etalons.
AB  - Poly(N-isopropylacrylamide) (pNIPAm) microgel-based etalons were used to
      fabricate systems that change visual color in response to light exposure. These
      systems were fabricated by adding pH responsive microgel-based etalons to a
      solution composed of the photoacid o-nitrobenzaldehyde (o-NBA). Upon exposure of
      this system to ultraviolet (UV) irradiation, the photoacid released a proton,
      lowering the pH of the solution. Since the pNIPAm microgel-based etalon was
      responsive to pH, the etalon changed its optical properties and, hence, visual
      color. We went on to show that patterned etalons could be fabricated, which only
      contained pH-responsive microgels in specific regions. These etalons only changed
      color in the pH-responsive regions, to yield patterns that change color upon UV
      light exposure. Finally, the color of the etalon was shown to be fully reversible
      and could be switched multiple times. These unique systems could potentially be
      used for display technologies, and as a controlled/triggered drug delivery
      system.

PMID- 24916053
TI  - Platinum nanocatalysts loaded on graphene oxide-dispersed carbon nanotubes with
      greatly enhanced peroxidase-like catalysis and electrocatalysis activities.
AB  - A powerful enzymatic mimetic has been fabricated by employing graphene oxide (GO)
      nanocolloids to disperse conductive carbon supports of hydrophobic carbon
      nanotubes (CNTs) before and after the loading of Pt nanocatalysts. The resulting
      GOCNT-Pt nanocomposites could present improved aqueous dispersion stability and
      Pt spatial distribution. Unexpectedly, they could show greatly enhanced
      peroxidase-like catalysis and electrocatalysis activities in water, as evidenced
      in the colorimetric and electrochemical investigations in comparison to some
      inorganic nanocatalysts commonly used. Moreover, it is found that the new enzyme
      mimetics could exhibit peroxidase-like catalysis activity comparable to natural
      enzymes; yet, they might circumvent some of their inherent problems in terms of
      catalysis efficiency, electron transfer, environmental stability, and cost
      effectiveness. Also, sandwiched electrochemical immunoassays have been
      successfully conducted using GOCNT-Pt as enzymatic tags. Such a fabrication
      avenue of noble metal nanocatalysts loaded on well-dispersed conductive carbon
      supports should be tailored for the design of different enzyme mimics promising
      the extensive catalysis applications in environmental, medical, industrial, and
      particularly aqueous biosensing fields. 

PMID- 24916054
TI  - Comparison of the copy numbers of bovine leukemia virus in the lymph nodes of
      cattle with enzootic bovine leukosis and cattle with latent infection.
AB  - To establish a diagnostic index for predicting enzootic bovine leukosis (EBL),
      proviral bovine leukemia virus (BLV) copies in whole blood, lymph nodes and
      spleen were examined by quantitative real-time PCR (qPCR). Cattle were divided
      into two groups, EBL and BLV-infected, based on meat inspection data. The number
      of BLV copies in all specimens of EBL cattle was significantly higher than those
      of BLV-infected cattle (p < 0.0001), and the number of BLV copies in the lymph
      nodes was particularly large. Over 70 % of the superficial cervical, medial iliac
      and jejunal lymph nodes from EBL cattle had more than 1,000 copies/10 ng DNA,
      whereas lymph nodes from BLV-infected cattle did not. These findings suggest that
      the cattle harboring more than 1,000 BLV copies may be diagnosed with EBL.

PMID- 24916055
TI  - Phylogenetic and recombination analysis of the homing protein domain of grapevine
      fanleaf virus (GFLV) isolates associated with 'yellow mosaic' and 'infectious
      malformation' syndromes in grapevine.
AB  - The RNA2 of seven grapevine fanleaf virus (GFLV) isolates from vines with yellow
      mosaic (YM) symptoms from different origin were sequenced. These sequences showed
      a high variability in the homing protein (2A(HP)) and, in five of them, a
      putative recombination with arabis mosaic virus (ArMV) was detected. To
      investigate recombination frequency, the partial sequences of the 2A(HP) of 28
      additional GFLV isolates from nine different countries, showing either YM or
      infectious malformations (MF) symptoms, were obtained and compared with those of
      GFLV isolates from GenBank. The analysis confirmed the high level of sequence
      variability (up to 41 % at the nucleotide level) among isolates. In phylogenetic
      trees constructed using different approaches, the sequenced isolates always
      clustered in four conserved groups, three of which comprised YM strains (groups
      1, 2 and 3), and one (group 4) the MF strains. Potential interspecific
      recombination sites between GFLV and ArMV were predicted in the 2A(HP) gene of
      several isolates, all of which were associated with YM symptoms.

PMID- 24916056
TI  - Complete sequence of a novel duck astrovirus.
AB  - A duck astrovirus isolate CPH (DAstV/CPH) detected from newly hatched ducklings
      was sequenced. The 7463-nt-long genome contained three open reading frames (ORFs)
      that were in three different frames, as seen in DAstV/C-NGB. Sequence comparison
      and phylogenetic analysis based on the full-length amino acid sequences of the
      three ORFs demonstrated that DAstV/CPH was highly divergent from previously known
      avastroviruses for which corresponding sequences are available. Genetic analysis
      of the complete ORF2 region revealed that mean amino acid genetic distances
      shared by DAstV/CPH with members of the three established avastrovirus species
      and other avastroviruses (except the chicken astrovirus GA2011 [CAstV/GA2011]
      like viruses) were between 0.577 and 0.787, suggesting that DAstV/CPH may
      represent an additional avastrovirus species. The mean amino acid genetic
      distance between DAstV/CPH and the CAstV/GA2011-like viruses was 0.366,
      demonstrating the difficulty in determining the taxonomic relationship of
      DAstV/CPH to the CAstV/GA2011-like viruses. Interestingly, analysis based on a
      portion of the ORF1b region indicated that DAstV/CPH was more closely related to
      the common-teal-origin astrovirus MPK514 than to the CAstV/GA2011-like viruses.
      The findings are likely to provide new insights into the ecology and evolution of
      avastroviruses.

PMID- 24916057
TI  - Laser pulse duration is critical for the generation of plasmonic nanobubbles.
AB  - Plasmonic nanobubbles (PNBs) are transient vapor nanobubbles generated in liquid
      around laser-overheated plasmonic nanoparticles. Unlike plasmonic nanoparticles,
      PNBs' properties are still largely unknown due to their highly nonstationary
      nature. Here we show the influence of the duration of the optical excitation on
      the energy efficacy and threshold of PNB generation. The combination of
      picosecond pulsed excitation with the nanoparticle clustering provides the
      highest energy efficacy and the lowest threshold fluence, around 5 mJ cm(-2), of
      PNB generation. In contrast, long excitation pulses reduce the energy efficacy of
      PNB generation by several orders of magnitude. Ultimately, the continuous
      excitation has the minimal energy efficacy, nine orders of magnitude lower than
      that for the picosecond excitation. Thus, the duration of the optical excitation
      of plasmonic nanoparticles can have a stronger effect on the PNB generation than
      the excitation wavelength, nanoparticle size, shape, or other "stationary"
      properties of plasmonic nanoparticles. 

PMID- 24916058
TI  - Evaluation of blood pressure and heart rate in patients with hypertension who
      received tapentadol extended release for chronic pain: a post hoc, pooled data
      analysis.
AB  - BACKGROUND AND OBJECTIVES: Hypertension is one of the most common co-existing
      conditions in patients with chronic pain, and the potential effects of an
      analgesic on heart rate and blood pressure are of particular concern for patients
      with hypertension. The purpose of this analysis was to evaluate changes in blood
      pressure and heart rate with tapentadol extended release (ER) treatment in
      patients with hypertension. METHODS: We performed a post hoc analysis of data
      pooled from three randomized, placebo- and active-controlled, phase III studies
      of tapentadol ER for managing chronic osteoarthritis knee (NCT00421928,
      NCT00486811) or low back (NCT00449176) pain (15-week, double-blind treatment
      period). Data were independently analyzed for patients with a listed medical
      history of hypertension at baseline and patients with at least one listed
      concomitant antihypertensive medication at baseline. Heart rate, systolic blood
      pressure (SBP), and diastolic blood pressure (DBP) were measured at each visit.
      RESULTS: In patients with a listed medical history of hypertension (n = 1,464),
      least-squares mean (LSM [standard error (SE)]) changes from baseline to endpoint
      with placebo, tapentadol ER, and oxycodone HCl controlled release (CR),
      respectively, were -0.7 (0.44), 0.2 (0.43), and -0.9 (0.45) beats per minute
      (bpm) for heart rate; -2.4 (0.64), -2.7 (0.64), and -3.7 (0.67) mmHg for SBP; and
      -1.0 (0.39), -1.3 (0.39), and -2.3 (0.41) mmHg for DBP; in patients with at least
      one listed concomitant antihypertensive medication (n = 1,376), the LSM (SE)
      changes from baseline to endpoint were -0.6 (0.45), 0.1 (0.44), and -0.7 (0.47)
      bpm for heart rate; -1.8 (0.66), -3.3 (0.65), and -3.7 (0.69) mmHg for SBP; and 
      0.7 (0.40), -1.4 (0.40), and -2.3 (0.42) mmHg for DBP. CONCLUSION: No clinically
      meaningful mean changes in heart rate or blood pressure were observed for the
      evaluated cohorts of patients with hypertension who were treated with tapentadol
      ER (100-250 mg twice daily).

PMID- 24916059
TI  - White-tailed deer are a biotic filter during community assembly, reducing species
      and phylogenetic diversity.
AB  - Community assembly entails a filtering process, where species found in a local
      community are those that can pass through environmental (abiotic) and biotic
      filters and successfully compete. Previous research has demonstrated the ability
      of white-tailed deer (Odocoileus virginianus) to reduce species diversity and
      favour browse-tolerant plant communities. In this study, we expand on our
      previous work by investigating deer as a possible biotic filter altering local
      plant community assembly. We used replicated 23-year-old deer exclosures to
      experimentally assess the effects of deer on species diversity (H'), richness
      (SR), phylogenetic community structure and phylogenetic diversity in paired
      browsed (control) and unbrowsed (exclosed) plots. Additionally, we developed a
      deer-browsing susceptibility index (DBSI) to assess the vulnerability of local
      species to deer. Deer browsing caused a 12 % reduction in H' and 17 % reduction
      in SR, consistent with previous studies. Furthermore, browsing reduced
      phylogenetic diversity by 63 %, causing significant phylogenetic clustering.
      Overall, graminoids were the least vulnerable to deer browsing based on DBSI
      calculations. These findings demonstrate that deer are a significant driver of
      plant community assembly due to their role as a selective browser, or more
      generally, as a biotic filter. This study highlights the importance of knowledge
      about the plant tree of life in assessing the effects of biotic filters on plant
      communities. Application of such knowledge has considerable potential to advance
      our understanding of plant community assembly. 

PMID- 24916060
TI  - Effects of pollination limitation and seed predation on female reproductive
      success of a deceptive orchid.
AB  - For many species of conservation significance, multiple factors limit
      reproduction. This research examines the contributions of plant height, number of
      flowers, number of stems, pollen limitation and seed predation to female
      reproductive success in the deceit-pollinated orchid, Cypripedium candidum. The
      deceptive pollination strategy employed by many orchids often results in high
      levels of pollen limitation. While increased floral display size may attract
      pollinators, C. candidum's multiple, synchronously flowering stems could promote
      selfing and also increase attack by weevil seed predators. To understand the
      joint impacts of mutualists and antagonists, we examined pollen limitation, seed
      predation and the effects of pollen source over two flowering seasons (2009 and
      2011) in Ohio. In 2009, 36 pairs of plants size-matched by flower number,
      receiving either supplemental hand or open pollination, were scored for fruit
      maturation, mass of seeds and seed predation. Pollen supplementation increased
      proportion of flowers maturing into fruit, with 87 % fruit set when hand
      pollinated compared with 46 % for naturally pollinated flowers. Inflorescence
      height had a strong effect, as taller inflorescences had higher initial fruit
      set, while shorter stems had higher predation. Seed predation was seen in 73 % of
      all fruits. A parallel 2011 experiment that included a self-pollination treatment
      and excluded seed predators found initial and final fruit set were higher in the
      self and outcross pollination treatments than in the open-pollinated treatment.
      However, seed mass was higher in both open pollinated and outcross pollination
      treatments compared with hand self-pollinated. We found greater female
      reproductive success for taller flowering stems that simultaneously benefited
      from increased pollination and reduced seed predation. These studies suggest that
      this species is under strong reinforcing selection to increase allocation to
      flowering stem height. Our results may help explain the factors limiting seed
      production in other Cypripedium and further emphasize the importance of
      management in orchid conservation. 

PMID- 24916061
TI  - Gastroesophageal reflux symptoms and associated factors in adolescents: A
      community-based study.

PMID- 24916062
TI  - Molecular insight of isotypes specific beta-tubulin interaction of tubulin
      heterodimer with noscapinoids.
AB  - Noscapine and its derivatives bind stoichiometrically to tubulin, alter its
      dynamic instability and thus effectively inhibit the cellular proliferation of a
      wide variety of cancer cells including many drug-resistant variants. The tubulin
      molecule is composed of alpha- and beta-tubulin, which exist as various isotypes
      whose distribution and drug-binding properties are significantly different.
      Although the noscapinoids bind to a site overlapping with colchicine, their
      interaction is more biased towards beta-tubulin. In fact, their precise
      interaction and binding affinity with specific isotypes of beta-tubulin in the
      alphabeta-heterodimer has never been addressed. In this study, the binding
      affinity of a panel of noscapinoids with each type of tubulin was investigated
      computationally. We found that the binding score of a specific noscapinoid with
      each type of tubulin isotype is different. Specifically, amino-noscapine has the
      highest binding score of -6.4, -7.2, -7.4 and -7.3 kcal/mol with alphabetaI,
      alphabetaII, alphabetaIII and alphabetaIV isotypes, respectively. Similarly 10
      showed higher binding affinity of -6.8 kcal/mol with alphabetaV, whereas 8 had
      the highest binding affinity of -7.2, -7.1 and -7.2 kcal/mol, respectively with
      alphabetaVI, alphabetaVII and alphabetaVIII isotypes. More importantly, both
      amino-noscapine and its clinical derivative, bromo-noscapine have the highest
      binding affinity of -46.2 and -38.1 kcal/mol against alphabetaIII (overexpression
      of alphabetaIII has been associated with resistance to a wide range of
      chemotherapeutic drugs for several human malignancies) as measured using MM-PBSA.
      Knowledge of the isotype specificity of the noscapinoids may allow for
      development of novel therapeutic agents based on this class of drugs. 

PMID- 24916063
TI  - Neonatal intubation with direct laryngoscopy vs videolaryngoscopy: an extremely
      premature baboon model.
AB  - OBJECTIVE: To compare the ability to successfully intubate extremely preterm
      baboons using conventional direct laryngoscopy (DL) vs videolaryngoscopy.
      METHODS: A prospective randomized crossover study using experienced and
      inexperienced neonatal intubators. All participants were shown an educational
      video on intubation with each device, followed by attempt of the procedure. The
      time for successful intubation was the primary outcome. RESULTS: Seven subjects
      comprised the experienced group, while 10 individuals were in the inexperienced
      group. The overall intubation success rate was comparable between both devices
      (53% vs 26%, P = 0.09); however, mean time to intubate with the conventional
      laryngoscope was faster (25.5 vs 39.4 s, P = 0.02). Although both groups
      intubated faster with DL, it only reached statistical significance in the
      inexperienced group (27.0 vs 48.7 s, P < 0.05). CONCLUSION: Conventional DL and
      videolaryngoscopy are suitable modes for intubating extremely preterm baboons.
      Although experienced intubators prefer DL, intubation success rate and time to
      intubate with both devices were comparable. In inexperienced intubators,
      participants preferred and intubated faster with DL.

PMID- 24916064
TI  - Wet oxidation of sewage sludge: full-scale experience and process modeling.
AB  - Nowadays, sewage sludge management represents one of the most important issues in
      wastewater treatment. Within the European project "ROUTES," wet oxidation (WO)
      was proposed for sludge minimization. Four different types of sludge were treated
      in an industrial WO plant: (1) municipal primary sludge (chemical oxygen demand
      COD: 73.0 g/L; volatile suspended solid VSS: 44.1 g/L); (2) secondary sludge from
      an industrial wastewater treatment plant (WWTP) without primary sedimentation
      (COD: 71.8 g/L; VSS: 34.2 g/L); (3) secondary sludge from a mixed municipal and
      industrial WWTP without primary sedimentation (COD: 61.9 g/L; VSS: 38.7 g/L); and
      (4) mixed primary (70%) and secondary (30%) municipal sludge (COD: 81.2 g/L; VSS:
      40.6 g/L). The effect of process parameters (temperature, reaction time, oxygen
      dosage) on WO performance was investigated. Depending on operating conditions,
      VSS and COD removal efficiency varied in the range 80-97% and 43-71%,
      respectively. A correlation between process efficiency and the initial VSS/TSS
      (total suspended solids) ratio was highlighted. Furthermore, a mathematical model
      of WO process for simulating VSS and COD profiles was developed.

PMID- 24916065
TI  - Small molecule enhancers of rapamycin induce apoptosis in myeloma cells via
      GSK3A/B preferentially within a protective bone marrow microenvironment.

PMID- 24916067
TI  - Childhood mycosis fungoides: experience of 28 patients and response to
      phototherapy.
AB  - Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is rare
      in childhood. The prognosis and response to treatment are poorly described in
      children. The objective of the current study was to evaluate the response to
      phototherapy in a pediatric cohort. A retrospective cohort study of all patients
      diagnosed with MF before the age of 18 years and referred to the regional CTCL
      phototherapy service was performed between January 1990 and April 2012. Twenty
      eight patients were identified (13 boys, 15 girls). The mean age at presentation
      was 11.6 +/- 3.9 years. The hypopigmented variant was noted in 79% of patients.
      All patients had stage I disease (IA = 10, IB = 17, unknown = 1). The median
      follow-up after diagnosis was 43 months (range 6-274 mos). Narrowband ultraviolet
      B (NbUVB; 311 nm) was used as first-line phototherapy in 18 patients and psoralen
      (bath) plus ultraviolet A (PUVA) was used in 8 patients. Complete or partial
      response was observed in 19 of 22 patients (86%). A further course of
      phototherapy was required in 7 of 12 patients (58%) treated with NbUVB after a
      median of 4 months (range 4-29 mos). A further course of phototherapy was
      required in four of eight patients (50%) successfully treated with PUVA after a
      median of 45.5 months (range 30-87 mos). No disease progression was noted over
      the follow-up (median 43 mos). The majority of patients in our cohort had
      hypopigmented MF. Phototherapy offers an effective option for treatment of
      childhood MF, although the period of remission may be greater in patients treated
      with PUVA. 

PMID- 24916066
TI  - Obesity and diabetes cause cognitive dysfunction in the absence of accelerated
      beta-amyloid deposition in a novel murine model of mixed or vascular dementia.
AB  - Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased
      risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown.
      We have created a novel mouse model that recapitulates features of T2DM and AD by
      crossing morbidly obese and diabetic db/db mice with APPDeltaNL/DeltaNLx
      PS1P264L/P264L knock-in mice. These mice (db/AD) retain many features of the
      parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of
      beta-amyloid (Abeta)). The combination of the two diseases led to additional
      pathologies-perhaps most striking of which was the presence of severe
      cerebrovascular pathology, including aneurysms and small strokes. Cortical Abeta
      deposition was not significantly increased in the diabetic mice, though overall
      expression of presenilin was elevated. Surprisingly, Abeta was not deposited in
      the vasculature or removed to the plasma, and there was no stimulation of
      activity or expression of major Abeta-clearing enzymes (neprilysin, insulin
      degrading enzyme, or endothelin-converting enzyme). The db/AD mice displayed
      marked cognitive impairment in the Morris Water Maze, compared to either db/db or
      APPDeltaNLx PS1P264L mice. We conclude that the diabetes and/or obesity in these
      mice leads to a destabilization of the vasculature, leading to strokes and that
      this, in turn, leads to a profound cognitive impairment and that this is unlikely
      to be directly dependent on Abeta deposition. This model of mixed or vascular
      dementia provides an exciting new avenue of research into the mechanisms
      underlying the obesity-related risk for age-related dementia, and will provide a
      useful tool for the future development of therapeutics.

PMID- 24916068
TI  - p27(kip1) deficiency accelerates dentin and alveolar bone formation.
AB  - To assess the role of p27(kip1) in regulating dental formation and alveolar bone
      development, we compared the teeth and mandible phenotypes of homozygous
      p27(kip1) -deficient (p27(-/-) ) mice with their wild-type littermates at 2 weeks
      of age. At 2 weeks of age, dental mineral density, dental volume and dentin
      sialoprotein-immunopositive areas were increased significantly, whereas the
      predentin area : total dentin area and biglycan-immunopositive area : dentin area
      ratios were decreased significantly in p27(-/-) mice compared with their wild
      type (WT) littermates. Mandible mineral density, cortical thickness, alveolar
      bone volume, type I collagen and osterix-immunopositive areas, osteoblast number
      and activity and mRNA expression of Runt-related transcription factor 2 (Runx2),
      alkaline phosphatase (ALP), osteocalcin and bone morphogenetic protein (bmp2)
      were all significantly increased in the mandibles, as was the number and surface
      of tartrate-resistant acid phosphatase-positive osteoclasts in the alveolar bone
      of p27(-/-) mice compared with their WT littermates. Furthermore, the percentage
      of proliferating cell nuclear antigen-positive cells in Hertwig's epithelial root
      sheath and protein expression of cyclin E and cyclin-dependent kinase 2 were
      increased significantly in p27(-/-) mice relative to their WT littermates. The
      results from this study indicate that p27 plays a negative regulatory role in
      dentin formation and alveolar bone development. 

PMID- 24916069
TI  - C2 photosynthesis generates about 3-fold elevated leaf CO2 levels in the C3-C4
      intermediate species Flaveria pubescens.
AB  - Formation of a photorespiration-based CO2-concentrating mechanism in C3-C4
      intermediate plants is seen as a prerequisite for the evolution of C4
      photosynthesis, but it is not known how efficient this mechanism is. Here, using
      in vivo Rubisco carboxylation-to-oxygenation ratios as a proxy to assess relative
      intraplastidial CO2 levels is suggested. Such ratios were determined for the C3
      C4 intermediate species Flaveria pubescens compared with the closely related C3
      plant F. cronquistii and the C4 plant F. trinervia. To this end, a model was
      developed to describe the major carbon fluxes and metabolite pools involved in
      photosynthetic-photorespiratory carbon metabolism and used quantitatively to
      evaluate the labelling kinetics during short-term (14)CO2 incorporation. Our data
      suggest that the photorespiratory CO2 pump elevates the intraplastidial CO2
      concentration about 3-fold in leaves of the C3-C4 intermediate species F.
      pubescens relative to the C3 species F. cronquistii. 

PMID- 24916070
TI  - Scratching the surface: genetic regulation of cuticle assembly in fleshy fruit.
AB  - The hydrophobic cuticular membrane of land plants performs a number of important
      roles during fruit development, including protection from a range of abiotic and
      biotic stresses. The components of the fleshy fruit cuticle are synthesized and
      secreted from the epidermal cells. While the biosynthetic and transport pathways
      of the cuticle have been thoroughly investigated for a number of decades, the
      regulatory mechanisms allowing fine tuning of cuticle deposition are only now
      beginning to be elucidated. Transcription factors belonging to the APETALA2,
      homeodomain-leucine zipper IV, and MYB families have been shown to be important
      regulators of both cuticle biosynthesis and epidermal cell differentiation,
      highlighting the connection between these processes. The involvement of MADS-box
      transcription factors demonstrates the link between fruit ripening and cuticle
      deposition. Epigenetic and post-transcriptional regulatory mechanisms also play a
      role in the control of cuticle biosynthesis, in addition to phytohormones, such
      as abscisic acid, that have been shown to stimulate cuticle deposition. These
      various levels of genetic regulation allow the plant constantly to maintain and
      adjust the cuticle in response to environmental and developmental cues. 

PMID- 24916071
TI  - Phytochrome B-mediated activation of lipoxygenase modulates an excess red light
      induced defence response in Arabidopsis.
AB  - Lipoxygenase (LOX), a non-haem-iron-containing dioxygenase, is activated under
      various biotic or abiotic stresses to trigger a series resistance response, but
      the molecular mechanism of LOX activation remains unclear. This work investigated
      the activation of LOX during the plant defence response induced by excess red
      light (RL). In conditions of RL-induced defence, Arabidopsis LOX activity and
      transcription levels of LOX2, LOX3, and LOX4 were both upregulated. Under RL,
      phytochrome B promoted the degradation of phytochrome-interacting factor 3
      (PIF3), a factor that inhibited the expression levels of LOXs, and thus the
      transcription levels of LOX2, LOX3, and LOX4 were increased. Upon pathogen
      infection, the activity of mitogen-activated protein kinase 3 (MPK3) and MPK6 was
      increased in plants pre-treated with RL. Moreover, experiments with the inhibitor
      PD98059 and mutants mpk3 and mpk6-2 demonstrated that MPK3 and MPK6 were both
      responsible for LOX activation. Further results showed that, in response to RL,
      an increase in cytoplasmic calcium concentration and upregulation of calmodulin 3
      (CaM3) transcript level occurred upstream of MPK3 and MPK6 activation.
      Collectively, these results suggested that activation of LOX both at the
      transcript level and in terms of activity modulates the defence response induced
      by RL, providing a new insight into the mechanistic study of LOX during plant
      defences. 

PMID- 24916072
TI  - A broad survey of hydraulic and mechanical safety in the xylem of conifers.
AB  - Drought-induced forest dieback has been widely reported over the last decades,
      and the evidence for a direct causal link between survival and hydraulic failure
      (xylem cavitation) is now well known. Because vulnerability to cavitation is
      intimately linked to the anatomy of the xylem, the main objective of this study
      was to better understand the xylem anatomical properties associated with
      cavitation resistance. An extensive data set of cavitation resistance traits and
      xylem anatomical properties was developed for 115 conifer species, with special
      attention given to the micro-morphology of bordered pits. The ratio of torus to
      pit aperture diameter, so-called torus overlap, increased with increasing
      cavitation resistance, while the flexibility of the margo does not seem to play a
      role, suggesting that air-seeding is located at the seal between the aspirated
      torus and pit aperture. Moreover, punctured tori were reported in various
      Pinaceae species. Species resistant to cavitation had thicker tracheid walls,
      while their lumen diameter (conduit size) was only slightly reduced, minimizing
      the impact on hydraulic conductance. The results also demonstrated (i) the
      existence of an indirect trade-off between hydraulic safety and mechanical
      strength; and (ii) a consistency between species distribution and xylem anatomy:
      species with a wide torus overlap and high valve effects are found in arid
      environments such as the Mediterranean region. 

PMID- 24916073
TI  - Fluid prescription practices of anesthesiologists managing patients undergoing
      elective colonoscopy: an observational study.
AB  - BACKGROUND: Routine fluid prescription is common practice amongst
      anesthesiologists caring for patients undergoing colonoscopy. However there is
      limited information about routine procedural fluid prescription practices of
      anesthesiologists in this setting. Routine fluid administration may also have
      important pharmaco-economic implications for the health care budget. Therefore we
      performed a prospective observational study assessing the fluid prescription
      practices of anesthesiologists caring for patients undergoing elective
      colonoscopy. METHODS: With Institutional Review Board approval, adult patients
      receiving procedural fluid intervention during elective colonoscopy were
      included. DATA COLLECTED: size of intravenous cannula inserted, volumes of fluid
      administered, adverse events, procedure duration, and pharmaco-economic costs
      associated with fluid prescription. Anesthesiologists and gastroenterologists
      were blinded to the study. RESULTS: We collected data on 289 patients who
      received fluid prescription by their attending anesthesiologist. Median patient
      age: 48 yrs (range 18-83), gender: 174 (60%) female; median duration of
      procedure: 24 minutes (range 12-48). Cannula size: 181 (63%) patients received a
      22G cannula or smaller. Median volume of fluid administered during the
      colonoscopy was 325 ml (range 0 to 1000 ml). Median duration of the procedure: 25
      minutes (range 12 to 48 minutes). Median volume of fluid administered in the post
      anaesthesia recovery unit: 450 ml (range 0 to 1000 ml). Fifteen patients (5%)
      became hypotensive during the procedure and two patients (<1%) developed
      hypotension in the PACU. There was no difference in the median fluid requirements
      between patients with hypotension and those without. Fluid volumes were strongly
      associated with increasing cannula diameter (p = 0.0001), however there was no
      association between fluid volumes administered and vasopressor use, peri
      procedural adverse events, or procedure duration. At our institution fluid
      therapy currently cost about AUD$4.90 per patient: 1 L crystalloid $1.18 and
      fluid delivery set $3.77 Our institution performs over 9000 endoscopic procedures
      annually with fluid therapy costing about $45,000/year. CONCLUSIONS: Routine
      fluid prescription by anesthesiologists managing patients undergoing colonoscopy
      was ineffective with low actual fluid volumes delivered during the procedure.
      There was no association between volumes of fluid delivered and procedural
      hypotension, adverse events, or procedure duration. Anesthesiologists should
      question the clinical and pharmaco-economic value of routine fluid administration
      for patients undergoing elective endoscopy.

PMID- 24916074
TI  - Runaway coevolution: adaptation to heritable and nonheritable environments.
AB  - Populations evolve in response to the external environment, whether abiotic
      (e.g., climate) or biotic (e.g., other conspecifics). We investigated how
      adaptation to biotic, heritable environments differs from adaptation to abiotic,
      nonheritable environments. We found that, for the same selection coefficients,
      the coadaptive process between genes and heritable environments is much faster
      than genetic adaptation to an abiotic nonheritable environment. The increased
      rate of adaptation results from the positive association generated by reciprocal
      selection between the heritable environment and the genes responding to it. These
      associations result in a runaway process of adaptive coevolution, even when the
      genes creating the heritable environment and genes responding to the heritable
      environment are unlinked. Although tightening the degree of linkage accelerates
      the coadaptive process, the acceleration caused by a comparable amount of
      inbreeding is greater, because inbreeding has a cumulative effect on reducing
      functional recombination over generations. Our results suggest that that
      adaptation to local abiotic environmental variation may result in the rapid
      diversification of populations and subsequent reproductive isolation not directly
      but rather via its effects on heritable environments and the genes responding to
      them. 

PMID- 24916075
TI  - Thermoresponsive ketoprofen-imprinted monolith prepared in ionic liquid.
AB  - A thermoresponsive imprinted monolith with the ability of molecular recognition
      for ketoprofen was prepared for the first time. The smart monolith was
      synthesized in a stainless steel column using acrylamide (AAm) and 2-acrylamide-2
      methyl propanesulfonic acid (AMPS) as functional monomers, which can form
      interpolymer complexation to restrict access of the analyte to the imprinted
      networks at low temperatures. To avoid a high back pressure of the column derived
      from neat dimethyl sulfoxide (DMSO) as a porogenic solvent that is needed to
      solve polar AMPS, an ionic liquid, [BMIM]BF4, was introduced into the pre
      polymerization mixture. The molecular recognition ability towards ketoprofen of
      the resulting thermoresponsive molecularly imprinted polymer (MIP) monolith
      displayed significant dependence on temperature compared with a non-imprinted
      column (NIP), and the greatest imprinting factor was achieved at the transition
      temperature of 35  degrees C (above 10). Furthermore, the number of binding sites
      of the smart MIP monolith at 35  degrees C was about 76 times as large as that at
      25  degrees C. In addition, Freundlich analyses indicated that the
      thermoresponsive MIP monolith had homogeneous affinity sites at both 25 and 35 
      degrees C with heterogeneity index 0.9251 and 0.9851, respectively. 

PMID- 24916076
TI  - Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in
      the COS canine osteosarcoma cell line.
AB  - Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity
      in osteoblasts. We examined the expression and function of 5HTR1B in the COS
      canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of
      5HTR1B gene and protein expression were found between normal and malignant
      osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells
      but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused
      no change in cell viability. Rather incubation with the specific receptor
      antagonist SB224289 caused reduction in osteoblast viability, with this effect
      more substantial in osteosarcoma cells. Investigation of this inhibitory activity
      showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of
      phosphorylated levels of CREB and ERK, transcriptional regulators associated with
      serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling
      in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell
      line and highlight this receptor as a possible novel therapeutic target. 

PMID- 24916077
TI  - The association between managed care enrollments and potentially preventable
      hospitalization among adult Medicaid recipients in Florida.
AB  - BACKGROUND: The intent of adopting managed care plans is to improve access to
      health care services while containing costs. To date, there have been a number of
      studies that examine the relationship between managed care and access to health
      care. However, the results from previous studies have been inconsistent.
      Specifically, previous studies did not demonstrate a clear benefit of Medicaid
      managed care. In this study we have examine whether Medicaid managed care is
      associated with the probabilities of preventable hospitalizations. This study
      also analyzes the spillover effect of Medicaid managed care into Medicaid
      patients in traditional FFS plans and the interaction effects of other patient-
      and county-level variables on preventable hospitalizations. METHODS: The study
      included 254,321 Medicaid patients who were admitted to short-term general
      hospital in the 67 counties in Florida. Using 2008 hospital inpatient discharge
      data for working-age adult Medicaid enrollees (18-64 years) in Florida, we
      conduct multivariate logistic regression analyses to identify possible factors
      associated with preventable hospitalizations. The first model includes patient-
      and county-level variables. Then, we add interaction terms between Medicaid HMO
      and other variables such as race, rurality, market-level factors, and resource
      for primary care. RESULTS: The results show that Medicaid HMO patients are more
      likely to be hospitalized for ambulatory care sensitive conditions (ACSCs) (OR =
      1.30; CI = 1.21, 1.40). We also find that market structure (i.e., competition) is
      significantly associated with preventable hospitalizations. However, our study
      does not support that there are spillover effects of Medicaid managed care on
      preventable hospitalizations for other Medicaid recipients. We find that
      interactions between Medicaid managed care and race, rurality and market
      structure are significant. CONCLUSIONS: The results of our study show that the
      Medicaid managed care program in Florida was associated with an increase in
      potentially preventable hospitalizations for Medicaid enrollees. The results
      suggest that lower capitation rate has been associated with a greater likelihood
      of preventable hospitalizations for Medicaid managed care patients. Our findings
      also indicate that increased competition in the Medicaid managed care market has
      no clear benefit in Medicaid managed care patients.

PMID- 24916078
TI  - Striking subgroup differences in substance-related mortality after release from
      prison.
AB  - AIMS: To compare the incidence, timing and risk factors for substance-related
      death between Indigenous and non-Indigenous ex-prisoners in Queensland,
      Australia. DESIGN: Retrospective cohort study. SETTING: All adult prisons in the
      state of Queensland, Australia, linked to deaths registered in Australia.
      PARTICIPANTS/CASES: We obtained records for all adults released from prison in
      Queensland, Australia from 1 January 1994 to 31 December 2007. Among this cohort
      of 42 015 individuals we observed 82 315 releases from prison and 2158 deaths in
      the community by the end of 2007, of which 661 were substance-related deaths.
      MEASUREMENTS: Incarceration data were obtained from Queensland Corrective
      Services and linked probabilistically with deaths recorded in the Australian
      National Death Index. FINDINGS: In the first year after release, Indigenous ex
      prisoners were more likely to die from alcohol-related causes [hazard ratio (HR)
      = 1.9, 95% confidence interval (CI) = 1.1-3.1)] but less likely to die of drug
      related causes (HR = 0.34, 95%CI = 0.21-0.53) than were non-Indigenous ex
      prisoners. Among non-Indigenous prisoners only, the risk of substance-related
      death was significantly higher in the first 4 weeks [relative risk (RR) = 5.1,
      95% CI = 3.7-6.9] when compared with the risk after 1 year post-release. Most
      evaluated risk factors for substance-related death were similar for Indigenous
      and non-Indigenous ex-prisoners; however, the hazard of death increased with age
      more for Indigenous ex-prisoners (HR = 1.7 per decade of age, 95% CI = 1.4-2.1)
      than for non-Indigenous ex-prisoners (HR = 1.3, 95% CI = 1.2-1.4). CONCLUSIONS:
      In Australia, patterns of substance-related death in ex-prisoners differ markedly
      according to Indigenous status. Efforts to prevent substance-related deaths in ex
      prisoners should consider heterogeneity in the target population and tailor
      responses accordingly.

PMID- 24916079
TI  - New broad-spectrum beta-lactamases emerging among Enterobacteriaceae from healthy
      cats and dogs: a public health concern?

PMID- 24916080
TI  - When fathers are instant losers: homogenization of rDNA loci in recently formed
      Cardamine * schulzii trigenomic allopolyploid.
AB  - Recently formed allopolyploids represent an excellent system to study the impacts
      of hybridization and genomic duplication on genome structure and evolution. Here
      we explored the 35SrRNA genes (rDNA) in the Cardamine * schulzii allohexaploid
      that was formed by two subsequent hybridization events within the past c. 150 yr.
      The rDNA loci were analyzed by cloning, next generation sequencing (NGS), RT-PCR
      and FISH methods. The primary C. * insueta triploid hybrid derived from C.
      rivularis (?) and C. amara (?) had gene ratios highly skewed towards maternal
      sequences. Similarly, C. * schulzii, originating from the secondary hybridization
      event involving C. * insueta (?) and C. pratensis (?), showed a reduction in
      paternal rDNA homeologs despite an excess of chromosomes inherited from C.
      pratensis. We also identified novel rDNA loci in C. * schulzii, suggesting that
      lost loci might be slowly reinstalled by translocation (but not recombination) of
      genes from partner genomes. Prevalent clonal propagation of allopolyploids, C. *
      insueta and C. * schulzii, indicates that concerted evolution of rDNA may occur
      in the absence of extensive meiotic cycles. Adoption of NGS in rDNA variant
      analysis is highly informative for deciphering the evolutionary histories of
      allopolyploid species with ongoing homogenization processes. 

PMID- 24916083
TI  - Free will and punishment: a mechanistic view of human nature reduces retribution.
AB  - If free-will beliefs support attributions of moral responsibility, then reducing
      these beliefs should make people less retributive in their attitudes about
      punishment. Four studies tested this prediction using both measured and
      manipulated free-will beliefs. Study 1 found that people with weaker free-will
      beliefs endorsed less retributive, but not consequentialist, attitudes regarding
      punishment of criminals. Subsequent studies showed that learning about the neural
      bases of human behavior, through either lab-based manipulations or attendance at
      an undergraduate neuroscience course, reduced people's support for retributive
      punishment (Studies 2-4). These results illustrate that exposure to debates about
      free will and to scientific research on the neural basis of behavior may have
      consequences for attributions of moral responsibility. 

PMID- 24916084
TI  - Exploring Solomon's paradox: self-distancing eliminates the self-other asymmetry
      in wise reasoning about close relationships in younger and older adults.
AB  - Are people wiser when reflecting on other people's problems compared with their
      own? If so, does self-distancing eliminate this asymmetry in wise reasoning? In
      three experiments (N = 693), participants displayed wiser reasoning (i.e.,
      recognizing the limits of their knowledge and the importance of compromise and
      future change, considering other people's perspectives) about another person's
      problems compared with their own. Across Studies 2 and 3, instructing individuals
      to self-distance (rather than self-immerse) eliminated this asymmetry. Study 3
      demonstrated that each of these effects was comparable for younger (20-40 years)
      and older (60-80 years) adults. Thus, contrary to the adage "with age comes
      wisdom," our findings suggest that there are no age differences in wise reasoning
      about personal conflicts, and that the effects of self-distancing generalize
      across age cohorts. These findings highlight the role that self-distancing plays
      in allowing people to overcome a pervasive asymmetry that characterizes wise
      reasoning. 

PMID- 24916085
TI  - Longitudinal changes in adiposity during adolescence: a population-based cohort.
AB  - OBJECTIVE: We aimed to assess the trends in body mass index (BMI) and body fat
      percentage (BF%) from the age of 13 to 17 years and to evaluate how
      sociodemographic and behavioural characteristics at the age of 13  impact changes
      in BMI and BF%. SETTING: Porto, Portugal. PARTICIPANTS: We evaluated 1451
      adolescents in a community-based cohort. OUTCOME MEASURES: BMI z-scores were
      calculated according to CDC references. BF% was assessed by bioelectrical
      impedance. Variables with a significant effect in adiposity changes were
      identified through linear regression models. In girls, estimates were controlled
      for duration of follow-up, parental education, baseline BMI z-score, age at
      menarche and the interaction term baseline BMI z-score*age at menarche; in boys,
      adjustments were performed for duration of follow-up, parental education,
      baseline BMI z-score and the interaction term baseline BMI z-score*duration of
      follow-up. RESULTS: On average, BMI z-score decreased from the age of 13 to 17
      years (mean difference -0.20, 95% CI -0.23 to -0.16 among girls and -0.15, 95% CI
      -0.19 to -0.11 among boys). Accordingly, 12.4% of girls and 13% of boys moved to
      a lower BMI category and 2.2% of girls and 5.5% of boys to a higher category.
      There were sex differences in the significant determinants of adiposity trends.
      Among girls, BMI z-score significantly decreased with baseline BMI z-score (beta=
      0.163, 95% CI -0.204 to -0.122) and significantly increased with age at menarche
      (beta=0.078, 95% CI 0.050 to 0.107). Results were similar for BF%. Among boys,
      BMI z-score significantly increased with higher parental BMI, and BF% decreased
      among those who wished to look larger at the age of 13 (beta=-1.367, 95% CI 
      2.174 to -0.560), compared with those who were satisfied with their image.
      CONCLUSIONS: In adolescents, ageing resulted in a decrease in BMI z-scores and
      BF%. BMI and BF% at the age of 13 were the major determinants of the observed
      trends. Our results suggest that adolescence is a possible specific time window
      for intervention.

PMID- 24916086
TI  - In utero exposure to alcohol and puberty in boys: a pregnancy cohort study.
AB  - OBJECTIVES: Epidemiological studies have raised concerns about the reproductive
      consequences of in utero exposure to alcohol. Maternal lifestyle factors have
      been associated with altered pubertal development, but the impact of prenatal
      alcohol exposure on male puberty is unknown. Thus, the objective was to explore
      whether prenatal alcohol exposure alters pubertal development in boys. SETTING:
      Follow-up of a Danish pregnancy cohort. PARTICIPANTS: Sons (N=2522) of women who
      were enrolled in a Danish pregnancy cohort between 1984 and 1987. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Indicators of pubertal development, assessed by age
      at first nocturnal emission, voice break, acne and regular shaving. RESULTS: We
      found a tendency towards a later age at first nocturnal emission and voice break
      following in utero exposure to binge drinking. Boys exposed to >=5 binge drinking
      episodes during pregnancy experienced their first nocturnal emission 7.3 months
      (95% CI -2.8 to 17.4) later and voice break 4.9 months (95% CI -0.6 to 10.4)
      later than the unexposed boys. Results for average weekly alcohol consumption
      were in the same direction, but differences were smaller and not statistically
      significant. CONCLUSIONS: We found no strong support for the hypothesis that in
      utero exposure to weekly alcohol consumption is a risk factor for altered
      pubertal development, but a tendency towards delayed pubertal development among
      boys exposed to binge drinking during fetal life was observed. Longitudinal
      studies, with data collected as children go through puberty, are needed to
      explore this further.

PMID- 24916087
TI  - Treatment delay affects clinical severity of tuberculosis: a longitudinal cohort
      study.
AB  - OBJECTIVES: To describe the risk factors for treatment delay and the effect of
      delay on the severity of tuberculosis (TB) in a prospectively followed TB cohort
      at the Bandim Health Project in Guinea-Bissau. BACKGROUND: Treatment delay in
      patients with TB is associated with increased mortality and transmission of
      disease. However, it is not well described whether delay influences clinical
      severity at diagnosis. Previously reported risk factors for treatment delay vary
      in different geographical and cultural settings. Such information has never been
      investigated in our setting. Change in delay over time is rarely reported and our
      prospectively followed TB cohort gives an opportunity to present such data.
      PARTICIPANTS: Patients were included at the time of diagnosis at three local TB
      clinics and the national TB reference hospital. Inclusion criteria were age >15
      years and diagnosis of TB by either sputum examination or by the WHO clinical
      criteria. Patients with extrapulmonary TB were excluded. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The primary outcome was treatment delay. Delay was assessed by
      patient questionnaires. The secondary outcome was Bandim TBscore as a measure of
      TB morbidity and all-cause mortality. RESULTS: A total of 1424 persons were
      diagnosed with TB in the study area between 2003 and 2010. We included 973
      patients with TB in the study. The median treatment delay was 12.1 weeks. Risk
      factors for delay were low educational level, HIV-1+HIV-2 dual infection and
      negative sputum smear. TB treatment delay decreased by 10.3% (7.9-12.6%) per year
      during the study period. Delay was significantly associated with clinical
      severity at presentation with 20.8% severe TB cases in the low delay quartile
      compared with 33.9% if delay was over the median of 12.1 weeks. CONCLUSIONS: Long
      treatment delay was associated with more severe clinical presentation. Treatment
      delay in TB cases is decreasing in Guinea-Bissau.

PMID- 24916088
TI  - Systematic review of incidence and complications of herpes zoster: towards a
      global perspective.
AB  - OBJECTIVE: The objective of this study was to characterise the incidence rates of
      herpes zoster (HZ), also known as shingles, and risk of complications across the
      world. DESIGN: We systematically reviewed studies examining the incidence rates
      of HZ, temporal trends of HZ, the risk of complications including postherpetic
      neuralgia (PHN) and HZ-associated hospitalisation and mortality rates in the
      general population. The literature search was conducted using PubMed, EMBASE and
      the WHO library up to December 2013. RESULTS: We included 130 studies conducted
      in 26 countries. The incidence rate of HZ ranged between 3 and 5/1000 person
      years in North America, Europe and Asia-Pacific, based on studies using
      prospective surveillance, electronic medical record data or administrative data
      with medical record review. A temporal increase in the incidence of HZ was
      reported in the past several decades across seven countries, often occurring
      before the introduction of varicella vaccination programmes. The risk of
      developing PHN varied from 5% to more than 30%, depending on the type of study
      design, age distribution of study populations and definition. More than 30% of
      patients with PHN experienced persistent pain for more than 1 year. The risk of
      recurrence of HZ ranged from 1% to 6%, with long-term follow-up studies showing
      higher risk (5-6%). Hospitalisation rates ranged from 2 to 25/100 000 person
      years, with higher rates among elderly populations. CONCLUSIONS: HZ is a
      significant global health burden that is expected to increase as the population
      ages. Future research with rigorous methods is important.

PMID- 24916089
TI  - Incidence, prevalence and outcomes of rheumatic heart disease in South Africa: a
      systematic review protocol.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is the principal cause of acquired
      heart disease affecting people living largely in poverty and deprived conditions.
      Sub-Saharan Africa was long thought to be the hotspot of the disease but recent
      reports suggest that this is no longer the case. South Africa is the leading
      economic force within this region yet contends with continued extreme income
      disparities. It is of interest to ascertain whether the strides that have been
      made in healthcare since the democratic transition in South Africa have
      translated into decreased RHD burden. We therefore propose to review the current
      best estimates of incidence of newly diagnosed RHD and prevalence of existing RHD
      within the past two decades. We also propose to characterise the fatal and non
      fatal outcomes of RHD and identify any trends in this period. METHODS AND DESIGN:
      We plan to search electronic databases and reference lists of relevant articles
      published from April 1994 to April 2014. Studies will be included if they
      estimated one of the following epidemiological measures: incidence, prevalence,
      remission rate, relative risk of mortality or cause-specific mortality. For
      studies deemed eligible for inclusion, we will assess overall study quality,
      reliability and risk of bias using design-specific criteria. We will extract data
      using a standardised form and perform descriptive and quantitative analysis to
      assess RHD prevalence, mortality and morbidity. This review protocol is
      registered in the PROSPERO International Prospective Register of systematic
      reviews, registration number CRD42014007072. DISSEMINATION: Our planned review
      will provide healthcare providers, public health officials and policymakers with
      pooled contemporary data regarding RHD, in particular regarding the effect the
      new political dispensation has had on the burden of this preventable disease
      within South Africa. In addition, these important country-specific data could
      influence policy decisions regarding prevention, management and control of RHD.

PMID- 24916090
TI  - Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a
      systematic review and meta-analysis of long-term randomised controlled trials.
AB  - OBJECTIVES: To evaluate glycaemic durability with dipeptidyl peptidase-4 (DPP-4)
      inhibitors in type 2 diabetes. DESIGN: A systematic review and meta-analysis of
      long-term randomised trials of DPP-4 inhibitors on haemoglobin A1c (HbA1c) was
      conducted. Electronic searches were carried out on the following databases:
      MEDLINE, EMBASE, Scopus and Web of Knowledge to December 2013. Searches were
      supplemented by a review of trial registries and references from identified
      trials. Trials were included if they lasted at least 76 weeks, and had
      intermediate and final assessments of HbA1c. Citations and full-text articles
      were screened by two reviewers. A random effect model was used to pool data.
      PARTICIPANTS: Adults with type 2 diabetes. INTERVENTIONS: Any DPP-4 inhibitor
      (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin). OUTCOME
      MEASURES: The difference between final and intermediate HbA1c assessment was the
      primary outcome. RESULTS: We screened 461 citations and reviewed 12 articles
      reporting 12 trials in 14 829 participants. All trials were of 76 weeks duration
      at least. The difference in HbA1c changes between final and intermediate points
      averaged 0.22% (95% CI 0.15% to 0.29%), with high heterogeneity (I(2)=91%,
      p<0.0001). Estimates of differences were not affected by the analysis of six
      extension trials (0.24%, 0.02 to 0.46), or five trials in which a DPP-4 inhibitor
      was added to metformin (0.24%, 0.16 to 0.32). CONCLUSIONS: There is evidence that
      the effect of DPP-4 inhibitors on HbA1c in type 2 diabetes significantly declines
      during the second year of treatment. Future research should focus on the
      characteristics of patients that benefit most from DPP-4 inhibitors in terms of
      glycaemic durability.

PMID- 24916091
TI  - The association between objectively measured sitting and standing with body
      composition: a pilot study using MRI.
AB  - OBJECTIVE: To investigate the association between objectively measured sitting
      and standing, using a postural allocation technique, with MRI-assessed body
      composition. DESIGN: The present study was a cross-sectional pilot study.
      SETTING: Participants were examined at one centre located in London, UK.
      PARTICIPANTS: Normal weight Caucasian women (30.9+/-6.1 years; body mass index
      (BMI), 22.9+/-3.4 kg/m(2)) with desk-bound occupations were recruited to minimise
      variability in body composition outcomes. A convenience sample of 12 women was
      recruited in January 2014 from University College London. OUTCOME MEASURES: For
      each participant a number of body composition variables were attained from a
      single whole-body MRI session. Main outcome variables included: total and liver
      adiposity, visceral/subcutaneous fat ratio and BMI. Main exposure variables
      included: average sitting time, standing:sitting ratio and step count. Pearson
      correlations were carried out to examine associations between different activity
      categories and body composition variables. RESULTS: There were significant
      correlations between average daily sitting and liver adiposity and
      visceral/subcutaneous abdominal fat ratio (r=0.66 and 0.64, respectively);
      standing:sitting ratio was moderately correlated with liver adiposity and
      visceral/subcutaneous abdominal fat ratio (r=-0.53 and -0.45); average daily step
      count was moderately correlated with liver adiposity, total adiposity and
      visceral/subcutaneous abdominal fat ratio (r=-0.45, -0.46 and -0.51,
      respectively). CONCLUSIONS: This pilot study has provided preliminary evidence of
      relationships between objectively measured sitting and standing and precise
      measures of body composition.

PMID- 24916092
TI  - Available chlorine consumption from NaOCl solutions passively placed in
      instrumented human root canals.
AB  - AIM: To monitor chlorine consumption from nonagitated aqueous sodium hypochlorite
      (NaOCl) solutions in human root canals using a recently developed assay, which
      can determine the order of magnitude of available chlorine in small volumes of
      liquid. METHODOLOGY: The root canals of 80 extracted single-rooted human teeth
      were instrumented to ProTaper Universal F4 and irrigated using 1% NaOCl.
      Subsequently, canals were irrigated with copious amounts of deionized water to
      rinse out the residual chlorine. Subsequently, the teeth were sealed externally
      and placed in a water bath of 37  degrees C. Root canals were filled with NaOCl
      of 1%, 2.75%, 5.5%, or distilled water for 1, 10, 100 or 1000 min (n = 5 teeth
      per solution and time). Consumption of chlorine was measured using paper points
      pre-impregnated with 15% potassium iodide. Colour change of the paper points was
      determined photo-electronically, assessing their red value after absorbing
      solutions from root canals. Measurements were compared to a standard series of
      NaOCl down to 0.001% (n = 5 paper points per concentration). RESULTS: Red values
      of the paper points inserted into the root canal were affected by initial NaOCl
      concentration and time (two-way anova, P < 0.05). If NaOCl concentrations above
      0.1% are considered to be clinically relevant, then 5.5% NaOCl retained its
      activity in the root canal for more than 100 min, whereas 1% NaOCl lost its
      activity between 10 and 100 min. CONCLUSIONS: Nonagitated NaOCl solutions can
      remain biologically active in human root canals for extended time periods.

PMID- 24916093
TI  - Validation of the sleep disturbance scale for children and prevalence of parent
      reported sleep disorder symptoms in Chinese children.
AB  - OBJECTIVE: To translate and validate the Sleep Disturbance Scale for Children
      (SDSC), a promising questionnaire for use among children in epidemiological
      studies, in Chinese children. METHODS: In total, 3525 children aged 5-16 years
      were randomly selected from five primary schools in Shenyang. Internal
      consistency, reliability and factor analyses were undertaken to assess the
      construct validity of the SDSC. RESULTS: Internal consistency indicated adequate
      reliability (Cronbach's alpha=0.81). Factor analytic results indicated a six
      factor solution (ie, six types of sleep disorder) based on parent-reported sleep
      disorder symptoms. The mean total score of the SDSC was 39.28+/-7.83 and 156
      (4.43%) children were identified as suffering from parent-reported sleep
      disorder. The prevalence for each sleep type disorder ranged from 3.46% to 6.30%
      with the highest for sleep hyperhidrosis (SHY) and the lowest for disorders of
      initiating and maintaining sleep. Significant differences were found between boys
      and girls in the prevalence of sleep breathing disorders (6.51% vs. 3.72%), SHY
      (8.62% vs. 4.00%) and parent-reported sleep disorders (5.19% vs. 3.67%).
      CONCLUSIONS: The SDSC is reliable and useful in screening for parent-reported
      sleep disorders in Chinese children. Compared with other countries, parent
      reported sleep disorders among Chinese elementary school children were at a
      relatively low level of prevalence.

PMID- 24916094
TI  - An fMRI study of cerebrovascular reactivity and perfusion in obstructive sleep
      apnea patients before and after CPAP treatment.
AB  - OBJECTIVE: Cerebrovascular reactivity is impaired in patients suffering from
      obstructive sleep apnea syndrome (OSAS) as demonstrated by transcranial Doppler
      studies. We use magnetic resonance imaging techniques to investigate the
      anatomical distribution of cerebrovascular reactivity changes in patients with
      OSAS, as well as their evolution after therapeutic and sham continuous positive
      airway pressure (CPAP) treatment. METHODS: Twenty-three men with moderate or
      severe obstructive sleep apnea were compared to a healthy control group (n=7)
      using a breath-holding functional magnetic resonance imaging task and the flow
      sensitive alternating inversion recovery (FAIR) imaging before and after 2 months
      of therapeutic (active) or sub-therapeutic (sham) CPAP treatment. RESULTS:
      Significantly higher cerebrovascular reactivity was found in healthy controls as
      compared to patients in bilateral cortical and subcortical brain regions.
      Cerebrovascular reactivity increased with therapeutic CPAP in the thalamus and
      decreased with sham CPAP in medial frontal regions in OSAS patients. Duration of
      nocturnal hypoxemia and body mass index negatively correlated with
      cerebrovascular reactivity, particularly in the medial temporal lobe structures,
      suggesting a possible pathophysiological mechanism for hippocampal injury. There
      was no difference in perfusion between patients and control group, and no effect
      of CPAP or sham-CPAP treatment on perfusion in patients. CONCLUSIONS: Observed
      cerebrovascular reactivity changes were neither homogeneous throughout the brain
      nor followed vascular territories, but rather corresponded to underlying neuronal
      networks, establishing a relationship between cerebrovascular reactivity and
      surrounding neuronal activity.

PMID- 24916095
TI  - Metacognitive beliefs relate specifically to sleep quality in primary insomnia: a
      pilot study.
AB  - OBJECTIVE: To identify whether metacognitive aspects are a specific mental
      pattern of primary insomnia (PI) or an aspecific correlate of sleep alterations.
      METHODS: Sleep quality (Pittsburgh Sleep Quality Index: PSQI), anxiety (Self
      rating Anxiety State: SAS), depression (Beck Depression Inventory: BDI) and
      metacognition (Metacognitions Questionnaire - Insomnia: MCQ-I) were evaluated in
      24 PI patients, 13 snorers and 17 healthy controls. Rank-transformed PSQI, BDI,
      SAS and MCQ-I scores were submitted to one-way analysis of variance with group as
      a between-factor. PSQI was submitted to three-way analysis of covariance (ANCOVA)
      with MCQ-I, BDI or SAS as covariate and group as a between-factor. Post-hoc
      analyses were conducted using pairwise comparisons with Sidak correction.
      RESULTS: As expected, PSQI scores significantly differentiated the three groups,
      one from another: PI had highest scores followed by snorers and healthy controls.
      PI subjects had MCQ-I scores significantly higher than those of snorers and
      healthy controls; no difference between the latter groups was found. The ANCOVA
      on PSQI with MCQ-I as a covariate abolished the difference in sleep quality
      between PI and snorers, whereas covarying for BDI or SAS left the differences in
      sleep quality between the groups unchanged. CONCLUSION: These preliminary results
      lead to two main conclusions: (i) metacognitive aspects are more prominent in PI
      when compared to snorers and healthy controls; (ii) MCQI shows higher sensitivity
      in defining PI patients, with respect to PSQI. If these findings are confirmed
      and expanded by further studies, the development of a specific metacognitive
      model of primary insomnia may be warranted.

PMID- 24916096
TI  - Can nocturnal groaning be suspected by cardiorespiratory polygraphy?

PMID- 24916097
TI  - Brainstem infarction and sleep-disordered breathing in the BASIC sleep apnea
      study.
AB  - BACKGROUND: Association between cerebral infarction site and poststroke sleep
      disordered breathing (SDB) has important implications for SDB screening and the
      pathophysiology of poststroke SDB. Within a large, population-based study, we
      assessed whether brainstem infarction location is associated with SDB presence
      and severity. METHODS: Cross-sectional study was conducted on ischemic stroke
      patients in the Brain Attack Surveillance in Corpus Christi (BASIC) project.
      Subjects underwent SDB screening (median 13days after stroke) with a well
      validated cardiopulmonary sleep apnea-testing device (n=355). Acute infarction
      location was determined based on review of radiology reports and dichotomized
      into brainstem involvement or none. Logistic and linear regression models were
      used to test the associations between brainstem involvement and SDB or
      apnea/hypopnea index (AHI) in unadjusted and adjusted models. RESULTS: A total of
      38 participants (11%) had acute infarction involving the brainstem. Of those
      without brainstem infarction, 59% had significant SDB (AHI?10); the median AHI
      was 13 (interquartile range (IQR) 6, 26). Of those with brainstem infarction, 84%
      had SDB; median AHI was 20 (IQR 11, 38). In unadjusted analysis, brainstem
      involvement was associated with over three times the odds of SDB (odds ratio (OR)
      3.71 (95% confidence interval (CI): 1.52, 9.13)). In a multivariable model,
      adjusted for demographics, body mass index (BMI), hypertension, diabetes,
      coronary artery disease, atrial fibrillation, prior stroke/transient ischemic
      attack (TIA), and stroke severity, results were similar (OR 3.76 (95% CI: 1.44,
      9.81)). Brainstem infarction was also associated with AHI (continuous) in
      unadjusted (p=0.004) and adjusted models (p=0.004). CONCLUSIONS: Data from this
      population-based stroke study show that acute infarction involving the brainstem
      is associated with both presence and severity of SDB.

PMID- 24916098
TI  - A new fibrin sealant as a three-dimensional scaffold candidate for mesenchymal
      stem cells.
AB  - INTRODUCTION: The optimization of an organic scaffold for specific types of
      applications and cells is vital to successful tissue engineering. In this study,
      we investigated the effects of a new fibrin sealant derived from snake venom as a
      scaffold for mesenchymal stem cells, to demonstrate the ability of cells to
      affect and detect the biological microenvironment. METHODS: The characterization
      of CD34, CD44 and CD90 expression on mesenchymal stem cells was performed by flow
      cytometry. In vitro growth and cell viability were evaluated by light and
      electron microscopy. Differentiation into osteogenic, adipogenic and chondrogenic
      lineages was induced. RESULTS: The fibrin sealant did not affect cell adhesion,
      proliferation or differentiation and allowed the adherence and growth of
      mesenchymal stem cells on its surface. Hoechst 33342 and propidium iodide
      staining demonstrated the viability of mesenchymal stem cells in contact with the
      fibrin sealant and the ability of the biomaterial to maintain cell survival.
      CONCLUSIONS: The new fibrin sealant is a three-dimensional scaffolding candidate
      that is capable of maintaining cell survival without interfering with
      differentiation, and might also be useful in drug delivery. Fibrin sealant has a
      low production cost, does not transmit infectious diseases from human blood and
      has properties of a suitable scaffold for stem cells because it permits the
      preparation of differentiated scaffolds that are suitable for every need.

PMID- 24916099
TI  - Mating disruption of Spilonota ocellana and other apple orchard tortricids using
      a multispecies reservoir dispenser.
AB  - BACKGROUND: A new mating disruption formulation for population control of a wide
      range of tortricid pests, including Spilonota ocellana, was tested in Swedish
      apple orchards during 2012-2013. Owing to the characteristics of the local
      agricultural landscape, mating disruption was evaluated in isolated orchards
      rather than through an area-wide approach. Parameters such as trap shutdown,
      communication disruption in field cages, damage level and dispenser emission were
      measured as efficacy indicators. RESULTS: The test formulation reduced the
      catches in monitoring traps for the entire range of the tested species. In field
      cages, communication between sexes was disrupted for both Adoxophyes orana and
      Cydia pomonella. The fruit damage caused by leafrollers (including S. ocellana)
      was reduced by the treatment. The device showed a constant release of all
      components for the entire flight activity period of these pests. CONCLUSION:
      Single-orchard experiments showed a significant effect on field populations of
      the leafroller species complex. While promising, in light of the variability of
      the result, field scouting may be required to enable practitioners to estimate
      the density of the pests and avoid possible unexpected attacks. Additional
      experiments are needed to evaluate the efficacy of the product against C.
      pomonella.

PMID- 24916100
TI  - Surface-assisted laser desorption ionization mass spectrometry techniques for
      application in forensics.
AB  - Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is an
      excellent analytical technique for the rapid and sensitive analysis of
      macromolecules (>700 Da), such as peptides, proteins, nucleic acids, and
      synthetic polymers. However, the detection of smaller organic molecules with
      masses below 700 Da using MALDI-MS is challenging due to the appearance of matrix
      adducts and matrix fragment peaks in the same spectral range. Recently,
      nanostructured substrates have been developed that facilitate matrix-free laser
      desorption ionization (LDI), contributing to an emerging analytical paradigm
      referred to as surface-assisted laser desorption ionization (SALDI) MS. Since
      SALDI enables the detection of small organic molecules, it is rapidly growing in
      popularity, including in the field of forensics. At the same time, SALDI also
      holds significant potential as a high throughput analytical tool in roadside,
      work place and athlete drug testing. In this review, we discuss recent advances
      in SALDI techniques such as desorption ionization on porous silicon (DIOS), nano
      initiator mass spectrometry (NIMS) and nano assisted laser desorption ionization
      (NALDITM) and compare their strengths and weaknesses with particular focus on
      forensic applications. These include the detection of illicit drug molecules and
      their metabolites in biological matrices and small molecule detection from
      forensic samples including banknotes and fingerprints. Finally, the review
      highlights recent advances in mass spectrometry imaging (MSI) using SALDI
      techniques.

PMID- 24916101
TI  - A general copper-mediated nucleophilic 18F fluorination of arenes.
AB  - Molecules labeled with fluorine-18 are used as radiotracers for positron emission
      tomography. An important challenge is the labeling of arenes not amenable to
      aromatic nucleophilic substitution (SNAr) with [(18)F]F(-). In the ideal case,
      the (18)F fluorination of these substrates would be performed through reaction of
      [(18)F]KF with shelf-stable readily available precursors using a broadly
      applicable method suitable for automation. Herein, we describe the realization of
      these requirements with the production of (18)F arenes from pinacol-derived aryl
      boronic esters (arylBPin) upon treatment with [(18)F]KF/K222 and [Cu(OTf)2(py)4]
      (OTf = trifluoromethanesulfonate, py = pyridine). This method tolerates electron
      poor and electron-rich arenes and various functional groups, and allows access to
      6-[(18)F]fluoro-L-DOPA, 6-[(18)F]fluoro-m-tyrosine, and the translocator protein
      (TSPO) PET ligand [(18)F]DAA1106.

PMID- 24916102
TI  - Pre-school children have better spoken language when early implanted.
AB  - OBJECTIVES: The objectives of this study were: (1) to investigate the effect of
      age at cochlear implantation (CI) on vocabulary development; (2) to evaluate the
      age effect at CI surgery on the syntactic development; and (3) to examine the
      role of gender, age at first diagnosis and maternal education level on spoken
      language development. MATERIAL AND METHODS: Retrospective study. Thirty children
      with congenital severe- to -profound sensorineural hearing loss (SNHL) were
      sampled. They were diagnosed and fitted with hearing aids through six months of
      age. They were implanted between 8 and 17 months of age. The MacArthur-Bates
      Communicative Development Inventory (MCDI) was administrated at the age of 36
      months. The total productive vocabulary (word number raw score), the mean length
      of utterance (M3L) and the sentences complexity were analysed. RESULTS: The
      average word number raw score was 566.3 for the children implanted before 12
      months of age versus 355 for those implanted later. The M3L was 8.3 for those
      implanted under 1 year versus 4.2 of those implanted later. The average sentences
      complexity was 82.3% for those receiving CI before 12 months, while it was 24.4%
      for those underwent at CI after 12 months. Regression analysis revealed a highly
      significant and negative linear effect of age at CI surgery on all outcomes.
      Females had better outcomes. Age at diagnosis was not correlated with the
      linguistic results. The mother's education level had a positive significant
      effect on sentences complexity. CONCLUSION: The CI in pre-school children with
      SNHL implanted under 1 year has a positive effect on spoken language. Females
      seem to have better linguistic results. Finally high maternal educational level
      appears to have some positive effect on language development.

PMID- 24916103
TI  - EZH2 represses target genes through H3K27-dependent and H3K27-independent
      mechanisms in hepatocellular carcinoma.
AB  - Alterations of polycomb group (PcG) genes directly modulate the trimethylation of
      histone H3 lysine 27 (H3K27me3) and may thus affect the epigenome of
      hepatocellular carcinoma (HCC), which is crucial for controlling the HCC cell
      phenotype. However, the extent of downstream regulation by PcGs in HCC is not
      well defined. Using cDNA microarray analysis, we found that the target gene
      network of PcGs contains well-established genes, such as cyclin-dependent kinase
      inhibitors (CDKN2A), and genes that were previously undescribed for their
      regulation by PcG, including E2F1, NOTCH2, and TP53. Using chromatin
      immunoprecipitation assays, we demonstrated that EZH2 occupancy coincides with
      H3K27me3 at E2F1 and NOTCH2 promoters. Interestingly, PcG repress the expression
      of the typical tumor suppressor TP53 in human HCC cells, and an increased level
      of PcG was correlated with the downregulation of TP53 in certain HCC specimens.
      Unexpectedly, we did not find obvious H3K27me3 modification or an EZH2 binding
      signal at the TP53 promoters, suggesting that PcG regulates TP53 expression in an
      H3K27me3-independent manner. Finally, the reduced expression of PcGs effectively
      blocked the aggressive signature of liver cancer cells in vitro and in vivo.
      IMPLICATIONS: Taken together, our results establish the functional and
      mechanistic significance of certain gene regulatory networks that are regulated
      by PcGs in HCC.

PMID- 24916105
TI  - Ultrasound-diagnosed disorders in shoulder patients in daily general practice: a
      retrospective observational study.
AB  - BACKGROUND: Ultrasound imaging (US) is considered an accurate and widely
      available method to diagnose subacromial disorders. Yet, the frequency of the
      specific US-diagnosed shoulder disorders of patients with shoulder pain referred
      from general practice is unknown. We set out to determine the frequency of
      specific US-diagnosed shoulder disorders in daily practice in these patients and
      to investigate if the disorders detected differ between specific subgroups based
      on age and duration of pain. METHODS: A predefined selection of 240 ultrasound
      reports of patients with shoulder pain (20 reports for each month in 2011) from a
      general hospital (Orbis Medical Centre Sittard-Geleen, The Netherlands) were
      descriptively analysed. Inclusion criteria were: (i) referral from general
      practice, (ii) age >= 18 years, and (iii) unilateral shoulder examination.
      Subgroups were created for age (<65 years and >= 65 years) and duration of pain
      (acute or subacute (<12 weeks) and chronic (>= 12 weeks)). The occurrence of each
      specific disorder is expressed as absolute and relative frequencies. RESULTS:
      With 29%, calcific tendonitis was the most frequently diagnosed disorder,
      followed by subacromial-subdeltoid bursitis (12%), tendinopathy (11%), partial
      thickness tears (11%), full-thickness tears (8%) and AC-osteoarthritis (0.4%).
      For 40% of patients, no disorders were found on US. Significantly more full
      thickness-tears were found in the >= 65 years group. 'No disorders' was reported
      significantly more often in the <65 years group. The supraspinatus tendon was the
      most frequently affected tendon (72%). CONCLUSIONS: Calcific tendonitis is the
      most common US-diagnosed disorder affecting patients in general practice,
      followed by subacromial-subdeltoid bursitis, tendinopathy, partial- and full
      thickness tears and AC-osteoarthritis. Full-thickness tears were diagnosed
      significantly more frequently in patients >= 65 years, while 'no disorders' was
      more frequently reported in patients <65 years. Our findings imply that patients
      can be stratified into diagnostic subgroups, allowing more tailored treatment
      than currently applied.

PMID- 24916104
TI  - Transcriptional roles of PARP1 in cancer.
AB  - Poly (ADP-ribose) polymerase-1 (PARP1) is an abundant, ubiquitously expressed
      NAD(+)-dependent nuclear enzyme that has prognostic value for a multitude of
      human cancers. PARP1 activity serves to poly (ADP-ribose)-ylate the vast majority
      of known client proteins and affects a number of cellular and biologic outcomes,
      by mediating the DNA damage response (DDR), base-excision repair (BER), and DNA
      strand break (DSB) pathways. PARP1 is also critically important for the
      maintenance of genomic integrity, as well as chromatin dynamics and
      transcriptional regulation. Evidence also indicates that PARP-directed
      therapeutics are "synthetic lethal" in BRCA1/2-deficient model systems.
      Strikingly, recent studies have unearthed exciting new transcriptional-regulatory
      roles for PARP1, which has profound implications for human malignancies and will
      be reviewed herein.

PMID- 24916106
TI  - Community programmes for coronary heart disease in Spanish primary care.
AB  - OBJECTIVE: To explore the added value of community-orientated programmes aimed at
      enhancing healthy lifestyles associated with the key components of cardiovascular
      risk management (CVRM) in coronary heart disease (CHD) patients. METHODS:
      Observational study in Spain, including 36 practices, 36 health professionals,
      and 722 CHD patients (mean (SD) age 72 (11.73)). Our predictor variable of
      interest was reported deliveries from primary care practices (PCPs) concerning
      community-orientated programmes such as physical exercise and smoking cessation
      groups. Data were obtained through structured questionnaires administered to PCP
      health professionals. Our CVRM outcome measures were as follows: recorded risk
      factors, drug prescriptions, and intermediate patient outcomes (blood pressure
      levels, low-density lipoprotein cholesterol, and body mass index). RESULTS:
      Thirty practices delivered community programmes: most delivered one [17 (47.2%)
      practices] or two [11 (30.5%) practices]. These educational programmes aimed to
      encourage enhanced healthy lifestyles through group counselling sessions, mailed
      print material, and one-to-one counselling. In PCPs delivering community
      programmes, more patients received antihypertensives (89.7%), antiplatelet
      therapy (80.5%), and statins (70.8%) than those PCPs without programmes, although
      there were no statistically significant differences between them. CONCLUSIONS: No
      evidence was found for the added value of community-orientated CVRM programmes
      that could help health professionals refine criteria when including CHD patients
      in preventive programmes.

PMID- 24916107
TI  - Using A3 thinking to improve the STAT medication process.
AB  - BACKGROUND: Although the term STAT conveys a sense of urgency, it is sometimes
      used to circumvent a system that may be too slow to accomplish tasks in a timely
      manner. We describe a quality-improvement project undertaken by a US Department
      of Veterans Affairs (VA) hospital to improve the STAT medication process.
      METHODS: We adapted A3 Thinking, a problem-solving process common in Lean
      organizations, to our problem. In the discovery phase, a color-coded flow map of
      the existing process was constructed, and a real-time STAT order was followed in
      a modified "Go to the Gemba" exercise. In the envisioning phase, the team
      brainstormed to come up with as many improvement ideas as possible, which were
      then prioritized based on the anticipated effort and impact. The team then
      identified initial experiments to be carried out in the experimentation phase;
      each experiment followed a standard Plan-Do-Study-Act cycle. RESULTS: On average,
      the number of STAT medications ordered per month decreased by 9.5%. The average
      time from STAT order entry to administration decreased by 21%, and time from
      medication delivery to administration decreased by 26%. Improvements were also
      made in technician awareness of STAT medications and nurse notification of STAT
      medication delivery. CONCLUSIONS: Adapting A3 Thinking for process improvement
      was a low-cost/low-tech option for a VA facility. The A3 Thinking process led to
      a better understanding of the meaning of STAT across disciplines, and promoted a
      collaborative culture in which other hospital-wide problems may be addressed in
      the future.

PMID- 24916109
TI  - Nonaqueous capillary electrophoresis as separation technique to support
      metabolism studies by means of electrochemistry and mass spectrometry.
AB  - The first combination of electrochemistry (EC), NACE, and ESI-MS to mimic the
      metabolic fate of drugs is described. While the combination of EC, HPLC, and ESI
      MS has been used for this purpose before, NACE is able to deliver valuable
      additional information about possible metabolites of harmane when compared to
      HPLC. In this paper, NACE is used as a comprehensive separation technique in
      metabolism studies of harmane, a naturally occurring monoaminooxidase inhibitor,
      since it exhibits beneficial properties for the separation of polar compounds.
      Harmane is known to be metabolized via the oxidative metabolism catalyzed by
      cytochrome P450 enzymes, which are the most important metabolizing superfamily of
      enzymes in the human liver. The application of HPLC and NACE enabled the
      detection of 37 products in total, with 14 different mass-to-charge ratios. A
      total of 31 products could be detected in HPLC-MS and 26 in NACE-MS analysis. The
      combination of both NACE and RP-HPLC allows the identification of significantly
      more potential metabolites than any of the separation techniques alone. 

PMID- 24916108
TI  - Community empowerment and involvement of female sex workers in targeted sexual
      and reproductive health interventions in Africa: a systematic review.
AB  - BACKGROUND: Female sex workers (FSWs) experience high levels of sexual and
      reproductive health (SRH) morbidity, violence and discrimination. Successful SRH
      interventions for FSWs in India and elsewhere have long prioritised community
      mobilisation and structural interventions, yet little is known about similar
      approaches in African settings. We systematically reviewed community empowerment
      processes within FSW SRH projects in Africa, and assessed them using a framework
      developed by Ashodaya, an Indian sex worker organisation. METHODS: In November
      2012 we searched Medline and Web of Science for studies of FSW health services in
      Africa, and consulted experts and websites of international organisations. Titles
      and abstracts were screened to identify studies describing relevant services,
      using a broad definition of empowerment. Data were extracted on service-delivery
      models and degree of FSW involvement, and analysed with reference to a four-stage
      framework developed by Ashodaya. This conceptualises community empowerment as
      progressing from (1) initial engagement with the sex worker community, to (2)
      community involvement in targeted activities, to (3) ownership, and finally, (4)
      sustainability of action beyond the community. RESULTS: Of 5413 articles
      screened, 129 were included, describing 42 projects. Targeted services in FSW
      'hotspots' were generally isolated and limited in coverage and scope, mostly
      offering only free condoms and STI treatment. Many services were provided as part
      of research activities and offered via a clinic with associated community
      outreach. Empowerment processes were usually limited to peer-education (stage 2
      of framework). Community mobilisation as an activity in its own right was rarely
      documented and while most projects successfully engaged communities, few
      progressed to involvement, community ownership or sustainability. Only a few
      interventions had evolved to facilitate collective action through formal
      democratic structures (stage 3). These reported improved sexual negotiating power
      and community solidarity, and positive behavioural and clinical outcomes.
      Sustainability of many projects was weakened by disunity within transient
      communities, variable commitment of programmers, low human resource capacity and
      general resource limitations. CONCLUSIONS: Most FSW SRH projects in Africa
      implemented participatory processes consistent with only the earliest stages of
      community empowerment, although isolated projects demonstrate proof of concept
      for successful empowerment interventions in African settings.

PMID- 24916110
TI  - Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing.
AB  - RATIONALE: Individuals with naturally occurring loss-of-function proprotein
      convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low
      density lipoprotein cholesterol levels and protection against cardiovascular
      disease. OBJECTIVE: The goal of this study was to assess whether genome editing
      using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated system can efficiently introduce loss-of-function mutations into the
      endogenous PCSK9 gene in vivo. METHODS AND RESULTS: We used adenovirus to express
      CRISPR-associated 9 and a CRISPR guide RNA targeting Pcsk9 in mouse liver, where
      the gene is specifically expressed. We found that <3 to 4 days of administration
      of the virus, the mutagenesis rate of Pcsk9 in the liver was as high as >50%.
      This resulted in decreased plasma PCSK9 levels, increased hepatic low-density
      lipoprotein receptor levels, and decreased plasma cholesterol levels (by 35-40%).
      No off-target mutagenesis was detected in 10 selected sites. CONCLUSIONS: Genome
      editing with the CRISPR-CRISPR-associated 9 system disrupts the Pcsk9 gene in
      vivo with high efficiency and reduces blood cholesterol levels in mice. This
      approach may have therapeutic potential for the prevention of cardiovascular
      disease in humans.

PMID- 24916112
TI  - Spatial memory in sedentary and trained diabetic rats: molecular mechanisms.
AB  - Diabetes mellitus is a chronic disease that has been associated with memory loss,
      neurological disorders, and Alzheimer's disease. Some studies show the importance
      of physical exercise to prevent and minimize various neurological disorders. It
      is believed that the positive effects of exercise on brain functions are mediated
      by brain insulin and insulin-like growth factor-1 (IGF-1) signaling. In this
      study, we investigate the role of swimming exercise training on hippocampus
      proteins related to insulin/IGF-1 signaling pathway in Type 1 diabetic rats and
      its effects on spatial memory. Wistar rats were divided into four groups namely
      sedentary control, trained control, sedentary diabetic (SD), and trained diabetic
      (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program
      consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload
      corresponding to 90% of the anaerobic threshold. We employed ALX-induced diabetic
      rats to explore learning and memory abilities using Morris water maze test. At
      the end of the training period, the rats were sacrificed 48 h after their last
      exercise bout when blood samples were collected for serum glucose, insulin, and
      IGF-1 determinations. Hippocampus was extracted to determinate protein expression
      (IR, IGF-1R, and APP) and phosphorylation (AKT-1, AKT-2, Tau, and beta-amyloide
      proteins) by Western Blot analysis. All dependent variables were analyzed by two
      way analysis of variance with significance level of 5%. Diabetes resulted in
      hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however,
      in the training-induced group, there was a reduction in blood glucose in TD. The
      average frequency in finding the platform decreased in SD rats; however, exercise
      training improved this parameter in TD rats. Aerobic exercise decreased Tau
      phosphorylation and APP expression, and increased some proteins related to
      insulin/IGF-1 pathway in hippocampus of diabetic rats. Thus, these molecular
      adaptations from exercise training might contribute to improved spatial learning
      and memory in diabetic organisms.

PMID- 24916113
TI  - Aluminium electrodeposition under ambient conditions.
AB  - The electrodeposition of aluminium is demonstrated using a eutectic mixture of
      aluminium chloride and urea. The mixture is shown to be conducting through the
      formation of both cationic ([AlCl2.urean](+)) and anionic (AlCl4(-)) species and
      electrodeposition is achieved through the cationic species. The use of a biphasic
      system with the ionic liquid and a protective hydrocarbon layer allows metal
      deposition to be carried out in an environment with ambient moisture without the
      need for a glove box. A direct comparison is made between the AlCl3:urea and
      imidazolium chloride:AlCl3 systems and the differences in speciation and mass
      transport manifest themselves in different deposit morphologies. Brighteners
      which work in the chloroaluminate system such as toluene and LiCl are shown to be
      ineffective in the urea based system and the reasons for these differences are
      ascribed to the mechanism of the anodic reaction which is rate limiting. 

PMID- 24916111
TI  - Metabolic dysfunction consistent with premature aging results from deletion of
      Pim kinases.
AB  - RATIONALE: The senescent cardiac phenotype is accompanied by changes in
      mitochondrial function and biogenesis causing impairment in energy provision. The
      relationship between myocardial senescence and Pim kinases deserves attention
      because Pim-1 kinase is cardioprotective, in part, by preservation of
      mitochondrial integrity. Study of the pathological effects resulting from genetic
      deletion of all Pim kinase family members could provide important insight about
      cardiac mitochondrial biology and the aging phenotype. OBJECTIVE: To demonstrate
      that myocardial senescence is promoted by loss of Pim leading to premature aging
      and aberrant mitochondrial function. METHODS AND RESULTS: Cardiac myocyte
      senescence was evident at 3 months in Pim triple knockout mice, where all 3
      isoforms of Pim kinase family members are genetically deleted. Cellular
      hypertrophic remodeling and fetal gene program activation were followed by heart
      failure at 6 months in Pim triple knockout mice. Metabolic dysfunction is an
      underlying cause of cardiac senescence and instigates a decline in cardiac
      function. Altered mitochondrial morphology is evident consequential to Pim
      deletion together with decreased ATP levels and increased phosphorylated AMP
      activated protein kinase, exposing an energy deficiency in Pim triple knockout
      mice. Expression of the genes encoding master regulators of mitochondrial
      biogenesis, PPARgamma (peroxisome proliferator-activated receptor gamma)
      coactivator-1 alpha and beta, was diminished in Pim triple knockout hearts, as
      were downstream targets included in mitochondrial energy transduction, including
      fatty acid oxidation. Reversal of the dysregulated metabolic phenotype was
      observed by overexpressing c-Myc (Myc proto-oncogene protein), a downstream
      target of Pim kinases. CONCLUSIONS: Pim kinases prevent premature cardiac aging
      and maintain a healthy pool of functional mitochondria leading to efficient
      cellular energetics.

PMID- 24916114
TI  - Bovine and human lactoferricin peptides: chimeras and new cyclic analogs.
AB  - Lactoferrin (LF) is an important antimicrobial and immune regulatory protein
      present in neutrophils and most exocrine secretions of mammals. The antimicrobial
      activity of LF has been related to the presence of an antimicrobial peptide
      sequence, called lactoferricin (LFcin), located in the N-terminal region of the
      protein. The antimicrobial activity of bovine LFcin is considerably stronger than
      the human version. In this work, chimera peptides combining segments of bovine
      and human LFcin were generated in order to study their antimicrobial activity and
      mechanism of action. In addition, the relevance of the conserved disulfide bridge
      and the resulting cyclic structure of both LFcins were analyzed by using "click
      chemistry" and sortase A-catalyzed cyclization of the peptides. The N-terminal
      region of bovine LFcin (residues 17-25 of bovine LF) proved to be very important
      for the antimicrobial activity of the chimera peptides against E. coli, when
      combined with the C-terminal region of human LFcin. Similarly the cyclic bovine
      LFcin analogs generated by "click chemistry" and sortase A preserved the
      antimicrobial activity of the original peptide, showing the significance of these
      two techniques in the design of cyclic antimicrobial peptides. The mechanism of
      action of bovine LFcin and its active derived peptides was strongly correlated
      with membrane leakage in E. coli and up to some extent with the ability to induce
      vesicle aggregation. This mechanism was also preserved under conditions of high
      ionic strength (150 mM NaCl) illustrating the importance of these peptides in a
      more physiologically relevant system. 

PMID- 24916115
TI  - Influence of bovine lactoferrin on the growth of selected probiotic bacteria
      under aerobic conditions.
AB  - Bovine lactoferrin (bLf) is a natural glycoprotein, and it shows broad-spectrum
      antimicrobial activity. However, reports on the influences of bLf on probiotic
      bacteria have been mixed. We examined the effects of apo-bLf (between 0.25 and
      128 mg/mL) on both aerobic and anaerobic cultures of probiotics. We found that
      bLf had similar effects on the growth of probiotics under aerobic or anaerobic
      conditions, and that it actively and significantly (at concentrations of >0.25
      mg/mL) retarded the growth rate of Bifidobacterium bifidum (ATCC 29521), B.
      longum (ATCC 15707), B. lactis (BCRC 17394), B. infantis (ATCC 15697),
      Lactobacillus reuteri (ATCC 23272), L. rhamnosus (ATCC 53103), and L.
      coryniformis (ATCC 25602) in a dose-dependent manner. Otherwise, minimal
      inhibitory concentrations (MICs) were 128 or >128 mg/mL against B. bifidum, B.
      longum, B. lactis, L. reuteri, and L. rhamnosus (ATCC 53103). With regard to
      MICs, bLf showed at least four-fold lower inhibitory effect on probiotics than on
      pathogens. Intriguingly, bLf (>0.25 mg/mL) significantly enhanced the growth of
      Rhamnosus (ATCC 7469) and L. acidophilus (BCRC 14065) by approximately 40-200 %,
      during their late periods of growth. Supernatants produced from aerobic but not
      anaerobic cultures of L. acidophilus reduced the growth of Escherichia coli by
      about 20 %. Thus, bLf displayed a dose-dependent inhibitory effect on the growth
      of most probiotic strains under either aerobic or anaerobic conditions. An
      antibacterial supernatant prepared from the aerobic cultures may have significant
      practical use. 

PMID- 24916116
TI  - Highly conductive copper nano/microparticles ink via flash light sintering for
      printed electronics.
AB  - In this study, the size effect of copper particles on the flash light sintering
      of copper (Cu) ink was investigated using Cu nanoparticles (20-50 nm diameter)
      and microparticles (2 MUm diameter). Also, the mixed Cu nano-/micro-inks were
      fabricated, and the synergetic effects between the Cu nano-ink and micro-ink on
      flash light sintering were assessed. The ratio of nanoparticles to microparticles
      in Cu ink and the several flash light irradiation conditions (irradiation energy
      density, pulse number, on-time, and off-time) were optimized to obtain high
      conductivity of Cu films. In order to precisely monitor the milliseconds-long
      flash light sintering process, in situ monitoring of electrical resistance and
      temperature changes of Cu films was conducted during the flash light irradiation
      using a real-time Wheatstone bridge electrical circuit, thermocouple-based
      circuit, and a high-rate data acquisition system. Also, several microscopic and
      spectroscopic characterization techniques such as scanning electron microscopy, x
      ray diffraction, x-ray photoelectron spectroscopy, and Fourier transform infrared
      spectroscopy were used to characterize the flash light sintered Cu nano-/micro
      films. In addition, the sheet resistance of Cu film was measured using a four
      point probe method. This work revealed that the optimal ratio of nanoparticles to
      microparticles is 50:50 wt%, and the optimally fabricated and flash light
      sintered Cu nano-/micro-ink films have the lowest resistivity (80 MUOmega cm)
      among nano-ink, micro-ink, or nano-micro mixed films. 

PMID- 24916117
TI  - Tailoring of deep-red luminescence in Ca2SiO4:Eu(2+).
AB  - We report a new dicalcium silicate phosphor, Ca(2-x)Eu(x)SiO4, which emits red
      light in response to blue-light excitation. When excited at 450 nm, deep-red
      emission at 650 nm was clearly observed in Ca1.2Eu0.8SiO4, the external and
      internal quantum efficiencies of which were 44 % and 50 %, respectively. The red
      emission from Ca(2-x)Eu(x)SiO4 was strongly related to the peculiar coordination
      environments of Eu(2+) in two types of Ca sites. The red-emitting Ca2SiO4:Eu(2+)
      phosphors are promising materials for next-generation, white-light-emitting diode
      applications.

PMID- 24916118
TI  - Meta-analysis of randomized trials comparing combined compression and
      anticoagulation with either modality alone for prevention of venous
      thromboembolism after surgery.
AB  - BACKGROUND: Although venous thromboembolism (VTE) is an important cause of
      postoperative morbidity and mortality, there is still no consensus on the optimal
      strategy for VTE prevention after major surgery. The objective of this review was
      to determine the benefits and risks of thromboprophylaxis with both compression
      and anticoagulation, compared with either modality alone. METHODS: A systematic
      review of MEDLINE, CENTRAL and Embase databases was performed to identify
      eligible randomized trials. The literature search and data extraction were
      carried out independently by two reviewers. Outcomes of interest were deep vein
      thrombosis (DVT), pulmonary embolism, bleeding, limb injury and mortality.
      RESULTS: Twenty-five studies were eligible for inclusion. Adding compression to
      anticoagulation decreased the risk of DVT by 49 per cent (risk ratio (RR) 0.51,
      95 per cent confidence interval 0.36 to 0.73). The corresponding funnel plot
      suggested publication bias and, overall, the evidence for this comparison was
      judged to be of low quality. Adding anticoagulation to compression decreased the
      risk of DVT by 44 per cent (RR 0.56, 0.45 to 0.69) while increasing the risk of
      bleeding (RR 1.74, 1.29 to 2.34). There was no suggestion of publication bias and
      the evidence for this comparison was judged to be of moderate quality.
      CONCLUSION: Combined compression and anticoagulation is more effective at
      preventing postoperative DVT than either modality alone. However, adding
      anticoagulation to compression increases the risk of bleeding, and the evidence
      that adding compression to anticoagulation reduces VTE risk is of low quality.

PMID- 24916119
TI  - Ingestion and defecation of marine debris by loggerhead sea turtles, Caretta
      caretta, from by-catches in the South-West Indian Ocean.
AB  - Marine debris, caused by anthropogenic pollution, is a major problem impacting
      marine wildlife worldwide. This study documents and quantifies the ingestion and
      defecation of debris by 74 loggerhead sea turtles, Caretta caretta, in the South
      West Indian Ocean. Debris was found in 51.4% of gut or fecal samples of
      loggerheads by-catch from Reunion Island long liners. Anthropogenic debris was
      ubiquitous in our samples with plastics accounting for 96.2% of the total debris
      collected. No significant relationship was detected between the characteristics
      of ingested debris and the biometric characteristics of loggerheads. The number,
      weight, volume and mean length of debris were higher in gut content of deceased
      loggerheads than in fecal samples of live turtles, but not significantly, except
      for the mean length. This is the first record of debris ingestion by sea turtles
      in the Indian Ocean and our results highlight the magnitude of this pollution of
      the marine environment. 

PMID- 24916120
TI  - Angioarchitecture of gallbladder in pig: LM and SEM study on vascular
      microcorrosion casts.
AB  - The study focused on the description of pig gallbladder angioarchitecture, with
      particular emphasis on the specifics of the course of blood vessels in individual
      layers of the gallbladder wall. Furthermore, the vascular systems of the pig
      gallbladder were analyzed in terms of the adaptation of this organ to changes in
      its volume during cyclical bile storage and discharge. The gallbladder is
      supplied by the cystic artery, which in the pig represents a mixed pinnate and
      bipinnate pattern of branching. The light microscopic and scanning electron
      microscopic observations of three-dimensional vascular corrosion casts showed the
      presence of two main complex vascular networks in the wall of the gallbladder,
      one located in the subserosal and the other in the mucosa. The unique features in
      the pig, connected with the size of the gallbladder, is the well-developed
      horizontal venous plexus under folds of the mucosa, which is a voluminous
      reservoir of fluids absorbed from bile and vascular networks around mucous
      glands. Superficial blood vessels of the gallbladder run in vascular pairs or
      triads, where a single artery runs between two veins. The structures of blood
      flow control, that is, venous valves, were observed only in venules of the
      subserosal plexus. Spatial arrangement of the vascular network in the pig
      gallbladder shows functional plasticity during changes in gallbladder volume. The
      course of superficial blood vessels in the well-filled gallbladder is arcuate,
      while in the empty gallbladder it is undulated or spiral. In the mucosal and
      intramural vessels the direction of blood vessels may change from perpendicular
      to oblique.

PMID- 24916121
TI  - Ligand effect on the size, valence state and red/near infrared photoluminescence
      of bidentate thiol gold nanoclusters.
AB  - Synthesis and characterization of gold nanoclusters (Au NCs) stabilized by a
      zwitterion ligand (Zw) at different Au : Zw ratios are demonstrated. Au NCs
      exhibit photoluminescence (PL) emission which is tunable from the near infrared
      (805 nm) to the red spectral window (640 nm) and strongly influenced by the
      ligand shell size. Optical and chemical investigations suggest the presence of
      gold polymeric species and large nanoclusters for a molar ratio of Au : Zw = 1 :
      1. For 1 : 5 < Au : Zw < 1 : 1, Zw induces etching of the large clusters and the
      formation of a monolayer of the bidentate ligands on the Au NCs (cluster size ~7
      to 10 kDa) accompanied by red PL emission at lambda = 710 nm. A second organic
      layer starts to form for larger Zw fractions (Au : Zw < 1 : 5) as a result of
      electrostatic and covalent interactions of the zwitterion leading to an
      enhancement and a blue-shift of the PL emission. The effect of temperature and pH
      on the optical properties of gold clusters is strongly dependent on the ligand
      shell and demonstrates the importance of defining gold nanoclusters as
      supramolecular assemblies with a complex environment. 

PMID- 24916122
TI  - Prevalence and factors associated with hardcore smoking in Poland: findings from
      the Global Adult Tobacco Survey (2009-2010).
AB  - BACKGROUND: Estimating the prevalence of hardcore smoking and identifying linked
      factors is fundamental to improve planning and implementation of effective
      tobacco control measures. Given the paucity of data on that topic, we aimed to
      assess the prevalence of and factors associated with hardcore smoking in Poland.
      METHODS: We used data from the Global Adult Tobacco Survey (GATS). GATS is a
      representative, cross-sectional, household based survey conducted in Poland
      between 2009 and 2010. Binary logistic regression analysis was used to explore
      the associations of socio-demographic and smoking related variables with hardcore
      smoking among daily smokers. RESULTS: The prevalence of hardcore smoking was
      10.0% (13.0% among men and 7.3% among women) in the whole population of Poland at
      age 26 years and above. Hardcore smokers constitute 39.9% (41.6% among men and
      37.7% among women) of all daily smokers in analyzed age frame. Being older,
      having started smoking at earlier ages, living in large cities (in women only),
      being less aware of negative health effects of smoking, having less restrictions
      on smoking at home was associated with higher risk of being hardcore smoker.
      Educational attainment and economic activity were not associated with hardcore
      smoking among daily smokers. CONCLUSIONS: High prevalence of hardcore smokers may
      be a grand challenge for curbing non-communicable diseases epidemic in Poland.
      Our findings should urge policy makers to consider hardcore smoking issues while
      planning and implementing tobacco control policies. Prevention of smoking uptake,
      education programs, and strengthening cessation services appeared to be the top
      priorities.

PMID- 24916123
TI  - Potent inhibition of macrophage migration inhibitory factor (MIF) by
      myeloperoxidase-dependent oxidation of epicatechins.
AB  - MIF (macrophage migration inhibitory factor) plays a central role in the
      promotion and maintenance of the inflammatory response. It is implicated in a
      number of inflammatory diseases including sepsis, arthritis and colitis, and in
      diseases with an inflammatory component, such as atherosclerosis, diabetes and
      cancer. MIF has an unusual N-terminal proline with catalytic activity, and
      targeting of this residue by small-molecule inhibitors has been shown to
      interfere with the biological activity of MIF. The objective of the present study
      was to determine if MIF was susceptible to modification by epicatechins, a group
      of dietary flavonoids with known anti-inflammatory properties. Epicatechins are
      substrates for peroxidases including neutrophil-derived MPO (myeloperoxidase). In
      the present study we show that oxidation of the catechol moiety of epicatechins
      to an omicron-quinone by MPO generates potent MIF inhibitors. Near complete
      inhibition of MIF by the MPO/H2O2/epicatechin system was achieved at equimolar
      concentrations of epicatechin and MIF, even in the presence of other MPO
      substrates. We have characterized the modification introduced by oxidized (-)
      epicatechin on MIF by LC-MS (liquid chromatography MS) and found it to occur at
      the N-terminal proline. We propose that MIF inhibition by oxidized epicatechins
      contributes to the anti-inflammatory activity of these compounds. 

PMID- 24916124
TI  - New clade of enigmatic early archosaurs yields insights into early pseudosuchian
      phylogeny and the biogeography of the archosaur radiation.
AB  - BACKGROUND: The origin and early radiation of archosaurs and closely related taxa
      (Archosauriformes) during the Triassic was a critical event in the evolutionary
      history of tetrapods. This radiation led to the dinosaur-dominated ecosystems of
      the Jurassic and Cretaceous, and the high present-day archosaur diversity that
      includes around 10,000 bird and crocodylian species. The timing and dynamics of
      this evolutionary radiation are currently obscured by the poorly constrained
      phylogenetic positions of several key early archosauriform taxa, including
      several species from the Middle Triassic of Argentina (Gracilisuchus
      stipanicicorum) and China (Turfanosuchus dabanensis, Yonghesuchus sangbiensis).
      These species act as unstable 'wildcards' in morphological phylogenetic analyses,
      reducing phylogenetic resolution. RESULTS: We present new anatomical data for the
      type specimens of G. stipanicicorum, T. dabanensis, and Y. sangbiensis, and carry
      out a new morphological phylogenetic analysis of early archosaur relationships.
      Our results indicate that these three previously enigmatic taxa form a well
      supported clade of Middle Triassic archosaurs that we refer to as
      Gracilisuchidae. Gracilisuchidae is placed basally within Suchia, among the
      pseudosuchian (crocodile-line) archosaurs. The approximately contemporaneous and
      morphologically similar G. stipanicicorum and Y. sangbiensis may be sister taxa
      within Gracilisuchidae. CONCLUSIONS: Our results provide increased resolution of
      the previously poorly constrained relationships of early archosaurs, with
      increased levels of phylogenetic support for several key early pseudosuchian
      clades. Moreover, they falsify previous hypotheses suggesting that T. dabanensis
      and Y. sangbiensis are not members of the archosaur crown group. The recognition
      of Gracilisuchidae provides further support for a rapid phylogenetic
      diversification of crown archosaurs by the Middle Triassic. The disjunct
      distribution of the gracilisuchid clade in China and Argentina demonstrates that
      early archosaurs were distributed over much or all of Pangaea although they may
      have initially been relatively rare members of faunal assemblages.

PMID- 24916125
TI  - Next generation drying technologies for pharmaceutical applications.
AB  - Drying is a commonly used technique for improving the product stability of
      biotherapeutics. Typically, drying is accomplished through freeze-drying, as
      evidenced by the availability of several lyophilized products on the market.
      There are, however, a number of drawbacks to lyophilization, including the
      lengthy process time required for drying, low energy efficiency, high cost of
      purchasing and maintaining the equipment, and sensitivity of the product to
      freezing and various other processing-related stresses. These limitations have
      led to the search for next-generation drying methods that can be applied to
      biotherapeutics. Several alternative drying methods are reviewed herein, with
      particular emphasis on methods that are commonly employed outside of the
      biopharmaceutical industry including spray drying, convective drying, vacuum
      drying, microwave drying, and combinations thereof. Although some of the
      technologies have already been implemented for processing biotherapeutics, others
      are still at an early stage of feasibility assessment. An overview of each method
      is presented, detailing the comparison to lyophilization, examining the
      advantages and disadvantages of each technology, and evaluating the potential of
      each to be utilized for drying biotherapeutic products.

PMID- 24916126
TI  - Horseradish peroxidase-catalysed in situ-forming hydrogels for tissue-engineering
      applications.
AB  - In situ-forming hydrogels are an attractive class of implantable biomaterials
      that are used for biomedical applications. These injectable hydrogels are
      versatile and provide a convenient platform for delivering cells and drugs via
      minimally invasive surgery. Although several crosslinking methods for preparing
      in situ forming hydrogels have been developed over the past two decades, most
      hydrogels are not sufficiently versatile for use in a wide variety of tissue
      engineering applications. In recent years, enzyme-catalysed crosslinking
      approaches have been emerged as a new approach for developing in situ-forming
      hydrogels. In particular, the horseradish peroxidase (HRP)-catalysed crosslinking
      approach has received increasing interest, due to its highly improved and tunable
      capacity to obtain hydrogels with desirable properties. The HRP-catalysed
      crosslinking reaction immediately occurs upon mixing phenol-rich polymers with
      HRP and hydrogen peroxide (H2O2) in aqueous media. Based on this unique gel
      forming feature, recent studies have shown that various properties of formed
      hydrogels, such as gelation time, stiffness and degradation rate, can be easily
      manipulated by varying the concentrations of HRP and H2O2. In this review, we
      outline the versatile properties of HRP-catalysed in situ-forming hydrogels, with
      a brief introduction to the crosslinking mechanisms involved. In addition, the
      recent biomedical applications of HRP-catalysed in situ-forming hydrogels for
      tissue regeneration are described.

PMID- 24916127
TI  - Catecholase activity, DNA cleavage and cytotoxicity of six Zn(II) complexes
      synthesized from designed Mannich ligands: higher reactivity of mononuclear over
      dinuclear.
AB  - Six zinc(II) complexes have been synthesized from two designed Mannich-base
      ligands which consist of three dinuclear complex [Zn2(L(1))2X2] (1-3) and three
      mononuclear complex [ZnH(L(2))X2] (4-6), respectively, where X = Cl(-) (1,4), Br(
      ) (2,5), I(-) (3,6), as reported earlier by us (Sanyal et al., Inorg Chem 53:85
      96, 2014). The catecholase activity of the complexes has been investigated under
      completely aerobic conditions in DMF-water medium (9:1) at pH 8.5 against the
      model substrate 3,5-di-tert-butylcatechol (3,5-DTBC). Saturation kinetic studies
      show that the order of conversion of substrate to product (quinone) follows the
      trend 5 > 4 > 2 > 1 while 3 and 6 are inactive. The generation of phenoxyl
      radicals, confirmed by UV-vis and EPR spectral studies, is supposed to be
      responsible for the oxidation of 3,5-DTBC. The in vitro evaluation of 1-6
      comprises the study of their DNA-cleaving ability using plasmid DNA and the
      assessment of their cytotoxic activity against Jurkat (T cell lymphoma) cell line
      by MTT assay. The mechanisms of toxicity appeared to be predominantly by reactive
      oxygen species (ROS). The comparative analysis helps to arrive at the following
      facts under experimental conditions: (1) mononuclear species prevail over the
      dinuclear ones, unlike the behavior in phosphatase activity as reported in
      Inorganic Chemistry; (2) the halide substituents at the active site control the
      overall activity in the order: (a) In catecholase activity, Cl(-) < Br(-)
      (dinuclear) and Cl(-) > Br(-) (mononuclear) and (b) in biological activity, Cl(-)
      > Br(-) > I(-) regardless of nuclearity. 

PMID- 24916128
TI  - The reduction rates of DEPC-modified mutant Thermus thermophilus Rieske proteins
      differ when there is a negative charge proximal to the cluster.
AB  - Rieske and Rieske-type proteins are electron transport proteins involved in key
      biological processes such as respiration, photosynthesis, and detoxification.
      They have a [2Fe-2S] cluster ligated by two cysteines and two histidines. A
      series of mutations, L135E, L135R, L135A, and Y158F, of the Rieske protein from
      Thermus thermophilus has been produced which probe the effects of the neighboring
      residues, in the second sphere, on the dynamics of cluster reduction and the
      reactivity of the ligating histidines. These properties were probed using
      titrations and modifications with diethyl pyrocarbonate (DEPC) at various pH
      values monitored using UV-Visible and circular dichroism spectrophotometry. These
      results, along with results from EPR studies, provide information on ligating
      histidine modification and rate of reduction of each of the mutant proteins.
      L135R, L135A, and Y158F react with DEPC similarly to wild type, resulting in
      modified protein with a reduced [2Fe-2S] cluster in <90 min, whereas L135E
      requires >15 h under the same conditions. Thus, the negative charge slows down
      the rate of reduction and provides an explanation as to why negatively charged
      residues are rarely, if ever, found in the equivalent position of other Rieske
      and Rieske-type proteins. 

PMID- 24916129
TI  - High Resolution Imaging of Viscoelastic Properties of Intracranial Tumours by
      Multi-Frequency Magnetic Resonance Elastography.
AB  - PURPOSE: In recent years Magnetic Resonance Elastography (MRE) emerged into a
      clinically applicable imaging technique. It has been shown that MRE is capable of
      measuring global changes of the viscoelastic properties of cerebral tissue. The
      purpose of our study was to evaluate a spatially resolved three-dimensional multi
      frequent MRE (3DMMRE) for assessment of the viscoelastic properties of
      intracranial tumours. METHODS: A total of 27 patients (63 +/- 13 years) were
      included. All examinations were performed on a 3.0 T scanner, using a modified
      phase-contrast echo planar imaging sequence. We used 7 vibration frequencies in
      the low acoustic range with a temporal resolution of 8 dynamics per wave cycle.
      Post-processing included multi-frequency dual elasto-visco (MDEV) inversion to
      generate high-resolution maps of the magnitude |G*| and the phase angle phi of
      the complex valued shear modulus. RESULTS: The tumour entities included in this
      study were: glioblastoma (n = 11), anaplastic astrocytoma (n = 3), meningioma (n
      = 7), cerebral metastasis (n = 5) and intracerebral abscess formation (n = 1).
      Primary brain tumours and cerebral metastases were not distinguishable in terms
      of |G*| and phi. Glioblastoma presented the largest range of |G*| values and a
      trend was delineable that glioblastoma were slightly softer than WHO grade III
      tumours. In terms of phi, meningiomas were clearly distinguishable from all other
      entities. CONCLUSIONS: In this pilot study, while analysing the viscoelastic
      constants of various intracranial tumour entities with an improved spatial
      resolution, it was possible to characterize intracranial tumours by their
      mechanical properties. We were able to clearly delineate meningiomas from
      intraaxial tumours, while for the latter group an overlap remains in viscoelastic
      terms.

PMID- 24916130
TI  - Sub-micron phase coexistence in small-molecule organic thin films revealed by
      infrared nano-imaging.
AB  - Controlling the domain size and degree of crystallization in organic films is
      highly important for electronic applications such as organic photovoltaics, but
      suitable nanoscale mapping is very difficult. Here we apply infrared
      spectroscopic nano-imaging to directly determine the local crystallinity of
      organic thin films with 20-nm resolution. We find that state-of-the-art pentacene
      films (grown on SiO2 at elevated temperature) are structurally not homogeneous
      but exhibit two interpenetrating phases at sub-micrometre scale, documented by a
      shifted vibrational resonance. We observe bulk-phase nucleation of distinct
      ellipsoidal shape within the dominant pentacene thin-film phase and also further
      growth during storage. A faint topographical contrast as well as X-ray analysis
      corroborates our interpretation. As bulk-phase nucleation obstructs carrier
      percolation paths within the thin-film phase, hitherto uncontrolled structural
      inhomogeneity might have caused conflicting reports about pentacene carrier
      mobility. Infrared-spectroscopic nano-imaging of nanoscale polymorphism should
      have many applications ranging from organic nanocomposites to geologic minerals. 

PMID- 24916131
TI  - Measuring brand awareness as a component of eating habits in Indian children: the
      development of the IBAI questionnaire.
AB  - OBJECTIVE: To develop an instrument that allows one to estimate the Indian
      children's brand awareness of alimentary products. METHODS: The IBAI
      (International Brand Awareness Instrument), an age specific tool composed of 12
      sheets with images reporting brand logos of alimentary products, has been
      adjusted for the Indian context in order to investigate on infants' cognitive
      skills of recalling and recognizing. The IBAI was piloted in a sample of 100
      children aged from 3 to 10 y and enrolled in New Delhi schools. RESULTS: Children
      aged 7-10 y showed an higher brand awareness as compared to those of 3-6 y.
      CONCLUSIONS: The IBAI instrument may be a component for further analysis of the
      influence of food marketing on child's diet, foods' choices and preferences
      within the Indian social and cultural macro-context. Findings suggest that
      children over 6 y are particularly gullible by brands and TV promoted
      advertising. Prevention through information should, therefore be offered to
      school aged children and their parents, involving teachers, nutritionists and
      experts in developmental psychology also.

PMID- 24916132
TI  - Food packaged with toys: an investigation on potential obesogenic effects in
      Indian children.
AB  - OBJECTIVE: To investigate, in a large pan Indian sample of school children,
      whether gadgets (toys) added to food increase food consumption, and if
      contemporary exposure to TV and/or advertising is a further promoting factor.
      METHODS: A total of 1,680 Indian children were first randomized to food exposure
      with or without toy and then to a five-level exposure to TV viewing and
      advertising according to a 2 * 5 full factorial ad libitum eating design study.
      The sample size was computed to detect a difference of 20 Kcal of caloric intake
      (assuming the same standard deviation of 20 Kcal in both groups) between "food
      with gadget" (Toy) and "food alone" (No Toy) groups in each level of the exposure
      to TV and advertising factor, given an alpha error equal to 0.05 and a power of
      0.90. RESULTS: Mean caloric intake both in "Toy" and "No Toy" group was around
      223 Kcal. When considering exposure to TV and advertising, mean values varied
      negligibly between 222 and 225 Kcal. According to linear models for the effect of
      gadget and exposure to TV and/or advertising on children's intake, no significant
      adjusted associations were found, neither as main effects nor as interactions.
      CONCLUSIONS: Food consumption by children is not influenced by the presence of
      added toys, even after adjustment for several potential confounding factors. The
      city where they live and age significantly influences Indian children's caloric
      intake.

PMID- 24916133
TI  - Is my kid out of size? Indian mothers' desirability bias in evaluation of their
      children's weight.
AB  - OBJECTIVE: To quantify mothers' social desirability bias with respect to their
      children's weight in a cross-regional Indian setting. METHODS: The OBEY-AD was a
      cross-sectional study which has been realized in 7 Indian cities (Bengaluru,
      Mumbai, Chennai, Hyderabad, Kolkata, New Delhi and Surat), enroling 1,680
      children aged 3-11 y of which 50% were females. Children's BMI scores were
      computed, standardized according to WHO growth charts and categorized as Normal,
      Overweight, Obese and Underweight. Mothers were asked to judge the weight status
      of their children through an iconographic test, indicating the shape, which
      better mirrors the size of their kids. Socio-demographic data, especially
      employment, income and education, was accessed by administrating a cross
      sectional questionnaire to the mothers, involved for the study. RESULTS: Overall,
      369 children resulted as obese or overweight (23.5%). Out of them, 75% (278) were
      not recognized as such by their mothers. Such figures range from up to 76% in
      Chennai and Surat down to 72% in Hyderabad, Kolkata, New Delhi and Mumbai.
      Overall agreement between perceived and desired weight status of children was
      very poor (p < 0.001). Surprisingly, overall 10% of overweight/obese children
      were considered as even too lean by their mothers. Misperception of children's
      weight status seemed to be significantly related to urban differences and socio
      economic status. CONCLUSIONS: This study quantifies the extent of the so-called
      social desirability bias, namely mother's unconscious attitude to adapt empirical
      evidence to more culturally legitimized ideal-types of what their children's
      weight status is expected to be. Its association with westernized representations
      of leanness as evaluation criteria for beauty has important policy implications.

PMID- 24916134
TI  - Effect of inhaled magnesium sulfate on bronchial hyperresponsiveness.
AB  - OBJECTIVES: To determine the response of nebulized magnesium sulfate on the lung
      function of children with bronchial hyperresponsiveness. METHODS: Eighty-four
      children with asthma were divided into three groups randomly: magnesium sulfate
      (M), albuterol (A), and a combination of magnesium sulfate and albuterol (M + A).
      All patients were nebulized with acetylcholine, and then treated as designed.
      Lung function was compared between the three groups. RESULTS: Forced expiratory
      volume in first second (FEV1) significantly improved in all the three groups but
      it was better in (A) and (M + A) compared to (M) at 10 min and 20 min [10 min:
      1.26 L +/- 0.53 (A) vs. 1.10 L +/- 0.27 (M), 1.35 L +/- 0.59 (M + A) vs. 1.10 L
      +/- 0.27 (M), p < 0.05; 20 min: 1.32 L +/- 0.61 (A) vs. 1.17 L +/- 0.30 (M), 1.42
      L +/- 0.59 (M + A) vs. 1.17 L +/- 0.30 (M), p < 0.05]. Variation of FEV1, as
      absolute value at 10 min or 20 min over post-Ach FEV1 was significantly different
      in (A) or (M + A) compared to (M). CONCLUSIONS: Nebulized albuterol and magnesium
      sulfate + albuterol can more effectively improve FEV1 in children with bronchial
      hyperresponsiveness than nebulized magnesium sulfate at 10 min and 20 min after
      inhalation. It is further suggested that addition of magnesium sulfate to
      albuterol does not result in additional benefit.

PMID- 24916135
TI  - Compromised axonal functionality after neurodegeneration, concussion and/or
      traumatic brain injury.
AB  - Axonal swellings are almost universal in neurodegenerative diseases of the
      central nervous system, including Alzheimer's and Parkinson's disease.
      Concussions and traumatic brain injuries can also produce cognitive and
      behavioral deficits by compromising neuronal morphology. Using a spike metric
      analysis, we characterize computationally the effects of such axonal varicosities
      on spike train propagation by comparing Poisson spike train classes before and
      after propagation through a prototypical axonal enlargement, or focused axonal
      swelling. Misclassification of spike train classes and low-pass filtering of
      firing rate activity increases with more pronounced axonal injury. We show that
      confusion matrices and a calculation of the loss of transmitted information
      provide a very practical way to characterize how injured neurons compromise the
      signal processing and faithful conductance of spike trains. The method
      demonstrates that (i) neural codes encoded with low firing rates are more robust
      to injury than those encoded with high firing rates, (ii) classification depends
      upon the length of the spike train used to encode information, and (iii) axonal
      injuries reduce the variance of spike trains within a given stimulus class. The
      work introduces a novel theoretical and computational framework to quantify the
      interplay between electrophysiological dynamics with focused axonal swellings
      generated by injury or other neurodegenerative processes. It further suggests how
      pharmacology and plasticity may play a role in recovery of neural computation.
      Ultimately, the work bridges vast experimental observations of in vitro
      morphological pathologies with post-traumatic cognitive and behavioral
      dysfunction. 

PMID- 24916136
TI  - Tissue-engineered bone constructed in a bioreactor for repairing critical-sized
      bone defects in sheep.
AB  - PURPOSE: Repair of bone defects, particularly critical-sized bone defects, is a
      considerable challenge in orthopaedics. Tissue-engineered bones provide an
      effective approach. However, previous studies mainly focused on the repair of
      bone defects in small animals. For better clinical application, repairing
      critical-sized bone defects in large animals must be studied. This study
      investigated the effect of a tissue-engineered bone for repairing critical-sized
      bone defect in sheep. METHODS: A tissue-engineered bone was constructed by
      culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a
      porous beta-tricalcium phosphate ceramic (beta-TCP) scaffold in a perfusion
      bioreactor. A critical-sized bone defect in sheep was repaired with the tissue
      engineered bone. At the eighth and 16th week after the implantation of the tissue
      engineered bone, X-ray examination and histological analysis were performed to
      evaluate the defect. The bone defect with only the beta-TCP scaffold served as
      the control. RESULT: X-ray showed that the bone defect was successfully repaired
      16 weeks after implantation of the tissue-engineered bone; histological sections
      showed that a sufficient volume of new bones formed in beta-TCP 16 weeks after
      implantation. Eight and 16 weeks after implantation, the volume of new bones that
      formed in the tissue-engineered bone group was more than that in the beta-TCP
      scaffold group (P < 0.05). CONCLUSION: Tissue-engineered bone improved
      osteogenesis in vivo and enhanced the ability to repair critical-sized bone
      defects in large animals.

PMID- 24916138
TI  - Cavo-portal transposition in pediatric liver transplant recipients.
AB  - BACKGROUND: Cavo-portal transposition (CPT) at liver transplantation (LTx) allows
      portal revascularization of the liver in recipients in whom portal system
      thrombosis does not allow performance of porto-portal anastomosis. The aim was to
      present the cases of 2 children who underwent LTx and CPT in our institution.
      CASE REPORT: 1. A 10-year-old boy, after Kasai procedure and living donor LTx,
      was qualified for retransplantation 9 years after first LTx complicated with late
      portal vein thrombosis, portal hypertension, hypersplenism, and multiple GI
      bleeding episodes, after splenectomy and meso-caval shunt preventing GI bleeding.
      At retransplant surgery, CPT was done. Actual follow-up was 40 months. Doppler
      ultrasound and angio CT show normal flow within the graft's portal vein.
      Biochemical parameters were within normal range. There was no bleeding from the
      gastrointestinal tract. 2. A 14-month-old child after Kasai procedure was
      qualified for living donor liver transplantation. During surgery, thrombosis of
      the recipient portal system was found, which was not diagnosed before. The CPT
      was done. There were no complications during the postoperative course. The actual
      follow-up was 32 months, and the patient is doing well, with normal liver and
      renal function, without hypersplenism or ascites. There was no gastrointestinal
      bleeding. Doppler ultrasound showed normal intrahepatic portal and arterial flow
      in the transplanted liver. CONCLUSIONS: Cavo-portal transposition is an important
      option in portal vein revascularization in liver transplant recipients without
      access to the portal system. Long-term observation of these 2 cases did not show
      any late problems (e.g., bleeding from the gastrointestinal tract, renal
      function, hyperammonemia, ascites) related to cavo-portal transposition.

PMID- 24916137
TI  - Timing of premature physeal closure in Legg-Calve-Perthes Disease.
AB  - PURPOSE: Premature physeal closure of the proximal femoral physis has been
      reported in Legg-Calve-Perthes Disease (LCPD). However, the timing of its
      occurrence had not yet been reported. We proposed (1) to determine the timing of
      premature physeal closure in unilateral LCPD with serial radiographic evaluation,
      and (2) to evaluate the relationship between the premature physeal closure and
      Herring classification, leg-length discrepancy (LLD), Stulberg classification,
      and trochanteric overgrowth. METHODS: We performed a retrospective study with
      serial radiographs of 27 patients diagnosed with LCPD. The difference in the
      timing of physeal closure between the hips was calculated. The involved hip was
      classified according to Herring classification. The LLD and ATD index at latest
      follow up was measured. The mean values were calculated and statistical
      comparison of variables was done using the Fisher's exact test. RESULTS: The mean
      difference of physeal closure at the involved hip compared to the uninvolved side
      was 3.5 years (range, two to five years). Hips demonstrating premature physeal
      closure were associated with Herring B/C and C (p = 0.01) and LLD >1 cm (p =
      0.02). There is no correlation between Stulberg classification, trochanteric
      overgrowth and premature physeal closure (p = 0.06 and p = 0.19). CONCLUSIONS: We
      may expect premature physeal closure of the proximal femoral physis in patients
      with LCPD to occur 3.5 years earlier than normal hips. Presence of premature
      physeal closure can be an adjunct diagnostic tool in the prognostication of LCPD
      outcomes. Future studies directed toward premature physeal closure in LCPD and
      associated growth disturbances are necessary.

PMID- 24916139
TI  - Determination of toxic heavy metals in Echinodermata and Chordata species from
      South Korea.
AB  - This study aimed at analysing concentrations of heavy metals including arsenic,
      lead, cadmium, aluminium and mercury in commonly consumed seafood species
      belonging to Echinodermata (Anthocidaris crassispina and Stichopus japonicus) and
      Chordata (Halocynthia roretzi and Styela plicata). The samples were digested by a
      microwave system and analysed for As, Cd and Pb by inductively coupled plasma
      mass spectrometer, for Al by inductively coupled plasma-optical emission
      spectrometer and Hg by Direct Mercury Analyser. The analytical method was
      validated by determining sensitivity, linearity, precision, spiking recoveries
      and analysis of the Standard Reference Material (SRM) NIST 1566-b, an Oyster
      Tissue. Results showed considerably higher accumulation of Al and As in analysed
      samples, compared to Pb and Cd, while Hg had the lowest contamination. On
      comparison, the obtained results with the recommended standards by the Food and
      Agriculture Organization, European Commission and Ministry of Food and Drug
      Safety of Korea, it was concluded that the analysed seafoods were safe and thus
      would not pose a threat to consumers. 

PMID- 24916140
TI  - Young women's construction of their post-cancer fertility.
AB  - Younger women diagnosed with cancer often face compromised fertility as a result
      of their treatment. However, previous research has adopted a biomedical model of
      fertility and utilised hypothetico-deductive research methods which have not
      allowed for full exploration of women's subjectivity. This study explored younger
      women's construction of their fertility post-cancer, and their discussions of
      fertility with healthcare professionals, from a social constructionist
      epistemology. Semi-structured one-to-one interviews were conducted with eight
      women aged 18-26, across a variety of cancer types. Foucaultian Discourse
      Analysis identified three subject positions associated with fertility concerns:
      'Inadequate woman: Accepting the motherhood mandate'; 'Adequate woman: Resisting
      the motherhood mandate'; and 'Survival of the fittest: Woman as genetically
      defective'. Implications of these subject positions included feelings of
      inadequacy, fear and devastation; feeling undesirable to romantic partners; and
      concern about passing on cancer-positive genes. In describing healthcare
      professional interactions, women adopted positions of 'Satisfied patient';
      'Passive recipient patient'; or 'Resisting the passive patient position'.
      Accounts of inadequate information provision were associated with anger and
      frustration, whereas feeling adequately informed was associated with satisfaction
      at making decisions about fertility preservation. These results suggest that
      fertility is of importance to young women cancer survivors, and that compromised
      fertility can negatively impact subjectivity. 

PMID- 24916141
TI  - Comment on: First clinical manifestation of Brugada syndrome during pregnancy.

PMID- 24916142
TI  - Response to the letter regarding article "First clinical manifestation of Brugada
      syndrome during pregnancy".

PMID- 24916143
TI  - Influence of continuous negative pressure in the rat middle ear.
AB  - OBJECTIVES/HYPOTHESIS: High negative pressure in the middle ear was thought to be
      closely related to the etiology of retraction-type cholesteatoma. Recently, it
      has been detected that mechanical forces are important factors in epithelial
      turnover and affect cytoskeletal remodeling. Continuous negative pressure in the
      middle ear may possibly accelerate the proliferation and differentiation of
      epithelial cells of the tympanic membrane. STUDY DESIGN: Animal experimental
      study. METHODS: Eleven adult male Sprague-Dawley rats were used, and continuous
      negative pressure was loaded by connecting a catheter from the rat's middle ear
      to the supply route of an implantable microinfusion pump, iPRECIO. At 7 days
      after implantation of the device, an otoendoscopic examination and micro-computed
      tomography (CT) analysis of the temporal bone were performed; the temporal bones
      were then collected for histological and immunohistochemical analysis. The degree
      of proliferation and differentiation of epithelial cells of the tympanic membrane
      was investigated immunohistochemically using the anti-cytokeratin-5 and anti
      cytokeratin-10 antibodies. RESULTS: Otoendoscopic examination revealed retraction
      of the pars flaccida in all of the ears under negative pressure. In the micro-CT
      analysis, soft tissue density area in the hypotympanum was observed in all ears
      under negative pressure. Histological analysis revealed thickened epithelium of
      the pars flaccida. In this region, the thickness of layers with cytokeratin-5
      positive cells and cytokeratin-10-positive cells were increased. CONCLUSIONS:
      Continuous negative pressure in the middle ear can lead to thickening of the
      epithelium of the pars flaccida, and may accelerate the proliferation and
      differentiation of epithelial cells.

PMID- 24916144
TI  - Continuous noninvasive cardiac output in children: is this the next generation of
      operating room monitors? Initial experience in 402 pediatric patients.
AB  - BACKGROUND: Electrical Cardiometry(TM) (EC) estimates cardiac parameters by
      measuring changes in thoracic electrical bioimpedance during the cardiac cycle.
      The ICON((r)), using four electrocardiogram electrodes (EKG), estimates the
      maximum rate of change of impedance to peak aortic blood acceleration (based on
      the premise that red blood cells change from random orientation during diastole
      (high impedance) to an aligned state during systole (low impedance)). OBJECTIVE:
      To determine whether continuous cardiac output (CO) data provide additional
      information to current anesthesia monitors that is useful to practitioners.
      METHODS: After IRB approval and verbal consent, 402 children were enrolled. Data
      were uploaded to our anesthesia record at one-minute intervals. Ten-second
      measurements (averaged over the previous 20 heart beats) were downloaded to
      separate files for later comparison with routine OR monitors. RESULTS: Data from
      374 were in the final cohort (loss of signal or improper lead placement); 292,012
      measurements during 58,049 min of anesthesia were made in these children (1 day
      to 19 years and 1 to 107 kg). Four events had a >=25% reduction in cardiac index
      at least 1 min before a clinically important change in other monitored
      parameters; 18 events in 14 children confirmed manifestations of other
      hemodynamic measures; eight events may have represented artifacts because the
      observed measurements did not seem to fit the clinical parameters of the other
      monitors; three other events documented decreased stroke index with extreme
      tachycardia. CONCLUSIONS: Electrical cardiometry provides real-time
      cardiovascular information regarding developing hemodynamic events and
      successfully tracked the rapid response to interventions in children of all
      sizes. Intervention decisions must be based on the combined data from all
      monitors and the clinical situation. Our experience suggests that this type of
      monitor may be an important addition to real-time hemodynamic monitoring.

PMID- 24916145
TI  - 'Cool! and creepy': engaging with college student stakeholders in Michigan's
      biobank.
AB  - Large population biobanks, important resources for genomic research, also present
      ethical challenges. The Michigan BioTrust for Health makes dried bloodspots (DBS)
      leftover from newborn screening, including ~4.5 million collected before 2010
      without written consent, available for health research. Absent prospectively
      gathered consent and/or current engagement with 18- to 29-year olds, little is
      known about opinions and beliefs from this age group about use of the bloodspots
      for research. We engaged 2,101 students-BioTrust participants and their peers-at
      information booths at 20 college campuses across the state to educate youth about
      the BioTrust and gather information about consent preferences and about hopes and
      concerns about this public health program. We surveyed student stakeholder DBS
      research consent preferences and fielded a "postengagement" survey to gauge the
      attitudes of participants and to evaluate the campus engagement. The most
      prevalent themes in open-ended comments were support for biobank research and
      concern that Michiganders are not aware of their participation. While 78 % of
      students said they would, if asked, opt in to the BioTrust, half of these
      preferred to be contacted each time a researcher sought to use their DBS.
      Students reported great interest in the topic and strong likelihood to share what
      they had learned. BioTrust participants are interested in learning about their
      role in an initiative whose goals they widely support. Public engagement is
      particularly important to biobank participants who, absent traditional consent
      practices, are unaware of their participation. Health-fair style engagements were
      effective for targeting college-aged stakeholders, communicating complex
      messages, and likely increasing knowledge. Retrospective biobanks and biobanks
      that collect proxy consent need policies to respect those who would opt out and
      will need resources to educate participants and conduct community outreach that
      is a safeguard to public trust. 

PMID- 24916146
TI  - Dickkopf-1 expression is down-regulated during the colorectal adenoma-carcinoma
      sequence and correlates with reduced microvessel density and VEGF expression.
AB  - AIMS: Dickkopf-1 (Dkk1), an antagonist of the Wnt-beta-catenin signalling
      pathway, has been reported to play a role in cancer progression. However, little
      is known about the role of Dkk1 during the colorectal adenoma-carcinoma sequence.
      This study aimed to elucidate the role of Dkk1 in tumorigenesis and angiogenesis
      in colorectal cancer. METHODS AND RESULTS: We examined Dkk1 expression
      immunohistochemically in 476 colorectal tissue samples, including 46 sets of
      matched specimens. Dkk1 expression was down-regulated during the colorectal
      adenoma-carcinoma sequence, both among the 476 samples and in the 46 sets of
      matched specimens. Dkk1 expression was correlated with decreased microvessel
      density (P < 0.05) and VEGF expression. In-vitro 3D coculture experiments showed
      that Dkk1 overexpression in HCT116 cells inhibited tube-like structure formation
      and down-regulated VEGF expression in human umbilical vein endothelial cells.
      Xenografts of Dkk1-overexpressing colorectal cancer cells were smaller, and
      showed lower microvessel density and VEGF expression levels, than those of
      control cells. CONCLUSIONS: This study is the first to show the roles of Dkk1
      during the colorectal adenoma-carcinoma sequence, which may involve suppression
      of the tumorigenesis and angiogenesis of CRC. Dkk1 could therefore serve as a
      potential target for tumour therapy.

PMID- 24916147
TI  - Ramucirumab: first global approval.
AB  - Ramucirumab (CyramzaTM [US]), a fully human immunoglobulin G1 (IgG1) monoclonal
      antibody that inhibits vascular endothelial growth factor receptor-2 (VEGFR-2),
      has been developed by Eli Lilly (formerly ImClone Systems) for the treatment of
      cancer. Ramucirumab has received its first global approval in the US for use as
      monotherapy in the treatment of advanced or metastatic gastric cancer or gastro
      oesophageal junction adenocarcinoma in patients who experience disease
      progression on or after fluoropyrimidine- or platinum-containing chemotherapy.
      Ramucirumab is the first treatment to be approved by the US FDA for this setting.
      This article summarizes the milestones in the development of ramucirumab leading
      to this first approval for the treatment of gastric cancer and gastro-oesophageal
      junction adenocarcinoma. 

PMID- 24916148
TI  - Suture-related pseudoinfection after total hip arthroplasty.
AB  - Absorbable sutures are widely used for wound closure after total hip replacement.
      Here we present two cases of suture-related foreign-body reaction that perfectly
      mimicked a periprosthetic joint infection, with sterile abscess formation and
      physical and laboratory signs of inflammation acutely presenting 7-8 weeks after
      surgery, at the time of suture absorption. Both recurred with analogous timing
      after irrigation and debridement, likely due to re-using the same suture
      material. Multiple negative microbiological samples and positive histological
      samples showing a foreign-body reaction are the fundamental steps towards the
      diagnosis of a suture-related pseudoinfection (SRPI). Only three other cases have
      been reported to date, but the recurrence, together with the self-healing course
      after relapse, represents a completely novel feature and possibly the strongest
      demonstration of the supposed aetiopathogenesis. The knowledge of this possible
      complication leads to some clinical implications: all potential periprosthetic
      joint infections should routinely undergo not only microbiological but also
      histological sampling; caution should be used when recommending prosthesis
      exchange for potential infections occurring in the time range of suture
      absorption; lastly, if SRPI is suspected, a suture with low propensity to induce
      foreign-body reactions should be chosen after irrigation and debridement and the
      volume of absorbable material left in the wound should be as small as possible.

PMID- 24916149
TI  - Gastric dysrhythmias: a potential objective measure of nausea.
AB  - Nausea is a noxious, uncomfortable feeling usually located in the epigastrium.
      The pathophysiology of nausea encompasses brain-gut and gut-brain interaction.
      Nausea is associated with myoelectrical dysrhythmias of the stomach, an objective
      marker in the periphery. The aims of this review were to describe (1) the
      physiology of normal 3 cycle per minute (cpm) gastric myoelectrical activity and
      (2) conditions where shifts from normal 3 cpm gastric rhythms to gastric
      dysrhythmias are associated with the onset of nausea. Illusory self-motion,
      infusion of drugs such as morphine and glucagon, and ingestion of water or
      nutrient loads are several of the multitude of stimuli that induce acute nausea
      and a variety of gastric dysrhythmias such as tachygastrias (3.75-10 cpm) and
      bradygastrias (1.0-2.5  cpm). In nausea of motion sickness, increased nausea
      severity correlates with increased plasma vasopressin and epinephrine levels.
      Gastric dysrhythmias are also present in chronic gastrointestinal neuromuscular
      disorders such as gastroparesis. When gastric dysrhythmias resolve after drug or
      device therapies, nausea resolves. The shift in state from comfort in the
      epigastrium area and normal 3 cpm gastric rhythm to symptoms of nausea and
      gastric dysrhythmias represents dynamic gut-brain and brain-gut interactions that
      can be tracked by changes in gastric rhythm. CONCLUSIONS: (1) gastric
      dysrhythmias represent at least one peripheral mechanism underlying the symptom
      of nausea, and (2) gastric dysrhythmias are an objective biomarker for nausea and
      potential therapeutic targets for anti-nauseant therapies.

PMID- 24916150
TI  - Cuckoo hosts shift from accepting to rejecting parasitic eggs across their
      lifetime.
AB  - One of the best-known outcomes of coevolution between species is the rejection of
      mimetic parasite eggs by avian hosts, which has evolved to reduce costly cuckoo
      parasitism. How this behavioral adaptation varies along the life of individual
      hosts remains poorly understood. Here, we identify for the first time, lifetime
      patterns of egg rejection in a parasitized long-lived bird, the magpie Pica pica
      and show that, during the years they were studied, some females accept, others
      reject, and some others modify their response to model eggs, in all cases
      switching from acceptance to rejection. Females tested in their first breeding
      attempt always accepted the model egg, even those individuals whose mothers were
      egg rejecters. A longitudinal analysis showed that the probability of egg
      rejection increased with the relative age of the female, but was not related to
      the risk of parasitism in the population. We conclude that ontogeny plays a
      fundamental role in the process leading to egg rejection in magpies. 

PMID- 24916151
TI  - Postvaccinal, corticosteroid-resistant bullous pemphigoid in infancy: treatment
      with intravenous immunoglobulin.
AB  - Bullous pemphigoid is an autoimmune subepidermal blistering disorder that
      typically affects elderly adults but can also occur in childhood. We report on a
      3-month-old boy who developed bullous pemphigoid 1 week after the second routine
      administration of a hexavalent vaccine. The disease was resistant to standard
      therapies (including oral and topical corticosteroids) but was relieved by
      intravenous immunoglobulin treatment. There was no recurrence of bullous
      pemphigoid after the next vaccination (3 mos after discontinuation of steroids). 

PMID- 24916152
TI  - Phagocyte NADPH oxidase, chronic granulomatous disease and mycobacterial
      infections.
AB  - Infection of humans with Mycobacterium tuberculosis remains frequent and may
      still lead to death. After primary infection, the immune system is often able to
      control M. tuberculosis infection over a prolonged latency period, but a decrease
      in immune function (from HIV to immunosenescence) leads to active disease.
      Available vaccines against tuberculosis are restricted to BCG, a live vaccine
      with an attenuated strain of M. bovis. Immunodeficiency may not only be
      associated with an increased risk of tuberculosis, but also with local or
      disseminated BCG infection. Genetic deficiency in the reactive oxygen species
      (ROS)-producing phagocyte NADPH oxidase NOX2 is called chronic granulomatous
      disease (CGD). CGD is among the most common primary immune deficiencies. Here we
      review our knowledge on the importance of NOX2-derived ROS in mycobacterial
      infection. A literature review suggests that human CGD patient frequently have an
      increased susceptibility to BCG and to M. tuberculosis. In vitro studies and
      experiments with CGD mice are incomplete and yielded - at least in part -
      contradictory results. Thus, although observations in human CGD patients leave
      little doubt about the role of NOX2 in the control of mycobacteria, further
      studies will be necessary to unequivocally define and understand the role of ROS.

PMID- 24916153
TI  - Central role for protein kinase C in oxytocin and epidermal growth factor
      stimulated cyclooxygenase 2 expression in human myometrial cells.
AB  - BACKGROUND: Prostaglandins are important mediators of uterine contractility and
      cervical ripening during labour. Cyclooxygenase-2 (COX-2), also known as
      prostaglandin-endoperoxide synthase 2, is a rate limiting enzyme involved in the
      conversion of arachidonic acid into prostaglandins at parturition. In this paper,
      the pathways underlying agonist-induced cyclooxygenase-2 expression in human
      myometrial cells were studied. RESULTS: Myometrial cells were stimulated with
      different agonists: oxytocin (OXT), epidermal growth factor (EGF), interleukin
      1beta (IL1beta), and phorbol-12-myristate-13-acetate (PMA) alone and in the
      presence of specific signalling pathway inhibitors. The nuclear factor kappa
      light-chain-enhancer of activated B cells (NFKB) pathway was inhibited by means
      of the IKK-2 inhibitor TPCA-1. Signalling through extracellular signal-regulated
      kinases (ERK) was inhibited using the MEK1/2 inhibitor PD-184352.
      Bisindolylmaleimide-I was used to inhibit protein kinase C (PKC) signalling. COX
      2 expression and ERK phosphorylation were measured using immunoblotting.OXT
      induced COX-2 expression by activating PKC and ERK. EGF increased COX-2
      expression via stimulation of PKC, ERK and NFKB. As expected, the pro
      inflammatory cytokine IL1beta induced COX-2 expression by activating PKC- and
      NFKB-dependent pathways. Stimulation of PKC directly with PMA provoked strong COX
      2 expression. CONCLUSIONS: PKC plays a central role in OXT and EGF induced COX-2
      expression in human myometrial cells. However, other pathways, notably ERK and
      NFKB are also involved to an extent which depends on the type of agonist used.

PMID- 24916154
TI  - The fibrinogen gammaA/gamma' isoform does not promote acute arterial thrombosis
      in mice.
AB  - BACKGROUND: Elevated plasma fibrinogen is associated with arterial thrombosis in
      humans and promotes thrombosis in mice by increasing fibrin formation and
      thrombus fibrin content. Fibrinogen is composed of six polypeptide chains:
      (Aalpha, Bbeta, and gamma)2. Alternative splicing of the gamma chain leads to a
      dominant form (gammaA/gammaA) and a minor species (gammaA/gamma').
      Epidemiological studies have detected elevated gammaA/gamma' fibrinogen in
      patients with arterial thrombosis, suggesting that this isoform promotes
      thrombosis. However, in vitro data show that gammaA/gamma' is anticoagulant due
      to its ability to sequester thrombin and suggest its expression is upregulated in
      response to inflammatory processes. OBJECTIVE: To determine whether gammaA/gamma'
      fibrinogen is prothrombotic in vivo. METHODS: We separated gammaA/gammaA and
      gammaA/gamma' fibrinogen from human plasma-purified fibrinogen and determined the
      effects on in vitro plasma clot formation and on in vivo thrombus formation and
      circulating thrombin-antithrombin complexes in mice. RESULTS AND CONCLUSIONS:
      Both gammaA/gammaA and gammaA/gamma' fibrinogen were cleaved by murine and human
      thrombin and were incorporated into murine and human clots. When gammaA/gammaA or
      gammaA/gamma' was spiked into plasma, gammaA/gammaA increased the fibrin
      formation rate to a greater extent than gammaA/gamma'. In mice, compared to
      controls, gammaA/gammaA infusion shortened the time to carotid artery occlusion,
      whereas gammaA/gamma' infusion did not. Additionally, gammaA/gamma' infusion led
      to lower levels of plasma thrombin-antithrombin complexes following arterial
      injury, whereas gammaA/gammaA infusion did not. These data suggest that
      gammaA/gamma' binds thrombin in vivo and decreases prothrombotic activity.
      Together, these findings indicate that elevated levels of gammaA/gammaA
      fibrinogen promote arterial thrombosis in vivo, whereas gammaA/gamma' does not.

PMID- 24916155
TI  - Reduced 5-HT(1B) receptor binding in the dorsal brain stem after cognitive
      behavioural therapy of major depressive disorder.
AB  - Major depression is a significant contributor to the global burden of disease,
      and its pathophysiology is largely unknown. The serotonin hypothesis is, however,
      the model with most supporting data, although the details are only worked out to
      some extent. Recent clinical imaging measurements indeed imply a role in major
      depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5
      hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B
      receptor binding in the brain of MDD patients before and after psychotherapy. Ten
      patients with an ongoing untreated moderate depressive episode were examined with
      positron emission tomography (PET) and the 5-HT1B receptor selective radioligand
      [(11)C]AZ10419369, before and after treatment with internet-based cognitive
      behavioural therapy. All of the patients examined responded to treatment, and 70%
      were in remission by the time of the second PET measurement. A statistically
      significant 33% reduction of binding potential (BPND) was found in the dorsal
      brain stem (DBS) after treatment. No other significant changes in BPND were
      found. The DBS contains the raphe nuclei, which regulate the serotonin system.
      This study gives support for the importance of serotonin and the 5-HT1B receptor
      in the biological response to psychological treatment of MDD. 

PMID- 24916156
TI  - Biocatalytic anti-Prelog reduction of prochiral ketones with whole cells of
      Acetobacter pasteurianus GIM1.158.
AB  - BACKGROUND: Enantiomerically pure alcohols are important building blocks for
      production of chiral pharmaceuticals, flavors, agrochemicals and functional
      materials and appropriate whole-cell biocatalysts offer a highly
      enantioselective, minimally polluting route to these valuable compounds. At
      present, most of these biocatalysts follow Prelog's rule, and thus the (S)
      alcohols are usually obtained when the smaller substituent of the ketone has the
      lower CIP priority. Only a few anti-Prelog (R)-specific whole cell biocatalysts
      have been reported. In this paper, the biocatalytic anti-Prelog reduction of 2
      octanone to (R)-2-octanol was successfully conducted with high enantioselectivity
      using whole cells of Acetobacter pasteurianus GIM1.158. RESULTS: Compared with
      other microorganisms investigated, Acetobacter pasteurianus GIM1.158 was shown to
      be more effective for the reduction reaction, affording much higher yield,
      product enantiomeric excess (e.e.) and initial reaction rate. The optimal
      temperature, buffer pH, co-substrate and its concentration, substrate
      concentration, cell concentration and shaking rate were 35 degrees C, 5.0, 500
      mmol/L isopropanol, 40 mmol/L, 25 mg/mL and 120 r/min, respectively. Under the
      optimized conditions, the maximum yield and the product e.e. were 89.5% and
      >99.9%, respectively, in 70 minutes. Compared with the best available data in
      aqueous system (yield of 55%), the yield of (R)-2-octanol was greatly increased.
      Additionally, the efficient whole-cell biocatalytic process was feasible on a 200
      mL preparative scale and the chemical yield increased to 95.0% with the product
      e.e. being >99.9%. Moreover, Acetobacter pasteurianus GIM1.158 cells were proved
      to be capable of catalyzing the anti-Prelog bioreduction of other prochiral
      carbonyl compounds with high efficiency. CONCLUSIONS: Via an effective increase
      in the maximum yield and the product e.e. with Acetobacter pasteurianus GIM1.158
      cells, these results open the way to use of whole cells of this microorganism for
      challenging enantioselective reduction reactions on laboratory and commercial
      scales.

PMID- 24916157
TI  - Stability of smoking status in the US population: a longitudinal investigation.
AB  - AIMS: To determine smoking transitions in a representative sample of US adults.
      DESIGN: Longitudinal study using data from the National Epidemiologic Survey on
      Alcohol and Related Conditions (wave 1, 2001-02; wave 2, 2004-05). SETTING: The
      general US adult population. PARTICIPANTS: A total of 33 309 adults (53.6%
      female) classified as wave 1 current daily, current non-daily, former daily,
      former non-daily or never smokers. MEASUREMENTS: Smoking transitions were
      determined from waves 1 and 2 data. FINDINGS: Smoking status remained stable for
      the majority of current daily (79.8%), former daily (95.8%), former non-daily
      (96.3%) and never (97.1%) smokers. Among current non-daily smokers, 54.5% quit
      smoking while 22.5% increased to daily smoking. Current daily smokers who were
      older [30-44, odds ratio (OR) = 0.62; 95% confidence interval (CI) = 0.49-0.78;
      45+, OR = 0.75; 95% CI = 0.61-0.93] and unmarried (OR = 0.80, 95% CI = 0.66-0.96)
      were less likely to report smoking cessation. Current daily smokers who were
      Hispanic (OR = 2.15, 95% CI = 1.65-2.81) and college educated (OR = 1.27, 95% CI
      = 1.05-1.53) were more likely to report smoking cessation. Relapse in former
      daily smokers was greater in women (OR = 1.44, 95% CI = 1.01-2.06) and lower in
      older adults (OR = 0.44; 95% CI = 0.27-0.74). Smoking initiation occurred less in
      women (OR = 0.65; 95% CI = 0.49-0.87) and Hispanic adults (OR = 0.57; 95% CI =
      0.36-0.91) and more in unmarried adults (OR = 1.84; 95% CI = 1.37-2.47) and
      adults with less education (OR = 1.63; 95% CI = 1.09-2.44). CONCLUSIONS: From
      2001 to 2005, smoking status was extremely stable in the US population. Specific
      gender, race and educational groups need increased prevention and intervention
      efforts.

PMID- 24916158
TI  - Reconstitution of dynein transport to the microtubule plus end by kinesin.
AB  - Cytoplasmic dynein powers intracellular movement of cargo toward the microtubule
      minus end. The first step in a variety of dynein transport events is the
      targeting of dynein to the dynamic microtubule plus end, but the molecular
      mechanism underlying this spatial regulation is not understood. Here, we
      reconstitute dynein plus-end transport using purified proteins from S. cerevisiae
      and dissect the mechanism using single-molecule microscopy. We find that two
      proteins-homologs of Lis1 and Clip170-are sufficient to couple dynein to Kip2, a
      plus-end-directed kinesin. Dynein is transported to the plus end by Kip2, but is
      not a passive passenger, resisting its own plus-end-directed motion. Two
      microtubule-associated proteins, homologs of Clip170 and EB1, act as processivity
      factors for Kip2, helping it overcome dynein's intrinsic minus-end-directed
      motility. This reveals how a minimal system of proteins transports a molecular
      motor to the start of its track.DOI: http://dx.doi.org/10.7554/eLife.02641.001. 

PMID- 24916159
TI  - Mechanisms of organelle biogenesis govern stochastic fluctuations in organelle
      abundance.
AB  - Fluctuations in organelle abundance can profoundly limit the precision of cell
      biological processes from secretion to metabolism. We modeled the dynamics of
      organelle biogenesis and predicted that organelle abundance fluctuations depend
      strongly on the specific mechanisms that increase or decrease the number of a
      given organelle. Our model exactly predicts the size of experimentally measured
      Golgi apparatus and vacuole abundance fluctuations, suggesting that cells
      tolerate the maximum level of variability generated by the Golgi and vacuole
      biogenesis pathways. We observe large increases in peroxisome abundance
      fluctuations when cells are transferred from glucose-rich to fatty acid-rich
      environments. These increased fluctuations are significantly diminished in
      mutants lacking peroxisome fission factors, leading us to infer that peroxisome
      biogenesis switches from de novo synthesis to primarily fission. Our work
      provides a general framework for exploring stochastic organelle biogenesis and
      using fluctuations to quantitatively unravel the biophysical pathways that
      control the abundance of subcellular structures.DOI:
      http://dx.doi.org/10.7554/eLife.02678.001. 

PMID- 24916160
TI  - All Purkinje cells are not created equal.
AB  - Although the wiring of the cerebellar cortex appears to be uniform, the neurons
      in this region of the brain behave more differently from each other than
      previously thought. 

PMID- 24916161
TI  - A nonRD receptor-like kinase prevents nodule early senescence and defense-like
      reactions during symbiosis.
AB  - Rhizobia and legumes establish symbiotic interactions leading to the production
      of root nodules, in which bacteria fix atmospheric nitrogen for the plant's
      benefit. This symbiosis is efficient because of the high rhizobia population
      within nodules. Here, we investigated how legumes accommodate such bacterial
      colonization. We used a reverse genetic approach to identify a Medicago
      truncatula gene, SymCRK, which encodes a cysteine-rich receptor-like kinase that
      is required for rhizobia maintenance within the plant cells, and performed
      detailed phenotypic analyses of the corresponding mutant. The Medicago truncatula
      symCRK mutant developed nonfunctional and necrotic nodules. A nonarginine
      asparate (nonRD) motif, typical of receptors involved in innate immunity, is
      present in the SymCRK kinase domain. Similar to the dnf2 mutant, bacteroid
      differentiation defect, defense-like reactions and early senescence were observed
      in the symCRK nodules. However, the dnf2 and symCRK nodules differ by their
      degree of colonization, which is higher in symCRK. Furthermore, in contrast to
      dnf2, symCRK is not a conditional mutant. These results suggest that in M.
      truncatula at least two genes are involved in the symbiotic control of immunity.
      Furthermore, phenotype differences between the two mutants suggest that two
      distinct molecular mechanisms control suppression of plant immunity during
      nodulation. 

PMID- 24916162
TI  - Cognitive and psychophysiological correlates of disgust in obsessive-compulsive
      disorder.
AB  - OBJECTIVES: Evidence suggests that obsessive-compulsive disorder (OCD) is
      characterized by heightened self-reported disgust, however, it is unclear if this
      extends to physiology. The relationship between obsessive beliefs and disgust
      also remains poorly understood. Therefore, we examined whether the heightened
      trait and self-reported disgust observed in individuals with OCD is reflected in
      heightened physiological disgust responses. We also examined whether obsessive
      beliefs are associated with disgust responding. DESIGN: A 3 (group) * 6
      (stimulus) repeated measures design was used to examine disgust responses in
      individuals with OCD to six categories of image stimuli: body waste,
      contamination, injury, sociomoral, neutral, negative non-disgust. METHODS:
      Individuals with OCD (n = 25) were compared to individuals with non-OCD anxiety
      disorders (n = 21) and healthy participants (n = 25) with respect to trait, self
      reported, facial electromyographic and electrodermal disgust responses. RESULTS:
      Individuals with OCD showed greater disgust propensity and self-reported disgust
      to images of body waste compared to healthy and anxious participants, however,
      there were no group differences in physiological responses. After controlling for
      trait disgust, obsessive beliefs positively correlated with increased self
      reported disgust to neutral images and increased levator labii activity to
      negative non-disgusting images. CONCLUSIONS: Although individuals with OCD showed
      elevated disgust propensity and self-reported ratings of body waste stimuli,
      there was little evidence that OCD is characterized by an abnormal physiological
      disgust response. The intensity of obsessive beliefs was associated with a
      tendency to respond with disgust in contexts that are non-disgusting, indicating
      that obsessive beliefs may be implicated in pathological disgust. PRACTITIONER
      POINTS: Individuals with OCD display greater levels of disgust propensity and
      self-reported disgust to images of body waste compared to healthy control
      participants and individuals with non-OCD anxiety disorders. The abnormalities in
      self-reported disgust observed in those with OCD do not extend to abnormalities
      in electrodermal activity or facial electromyographic responses. Maladaptive
      obsessive beliefs commonly associated with OCD predict heightened disgust in
      contexts where objective sources of disgust are absent, even after controlling
      for trait disgust. Maladaptive obsessive beliefs may therefore be implicated in
      pathological disgust. This study used a heterogeneous OCD sample and future
      research is needed to determine whether the observed effects are greater for
      those with primarily washing and contamination symptoms. Although group
      differences emerged in self-reported disgust, further replications using measures
      of state anxiety are needed to rule out the possibility that heightened self
      reported disgust was confounded with co-occurring fear or general negative
      affect.

PMID- 24916164
TI  - Development of fruit color in Solanaceae: a story of two biosynthetic pathways.
AB  - This review highlights the major differences between the regulation of two
      important pathways namely anthocyanin and carotenoid pathways, responsible for
      fruit color generation in Solanaceae mediated by transcription factors (TFs). The
      anthocyanin pathway is regulated by a common set of TFs (MYB, MYC and WD40)
      belonging to specific families of DNA-binding proteins. Their regulation is aimed
      at controlling the type and amount of pigments produced and the physiological
      conditions (like pH) at which they are finally stored. In the carotenoid pathway,
      the color diversity depends on the quantity of pigment produced and the point
      where the pathway is arrested. TFs in the latter case are accordingly found to
      influence the sequestration and degradation of these pigments, which determines
      their final concentration in the tissue. TFs (phytochrome interacting factors,
      MADS-BOX, HB-ZIP and B-ZIP) also regulate important rate-determining steps, which
      decide the direction in which the pathway proceeds and the point at which it is
      terminated. In the absence of a clear pattern of TF-mediated regulation, it is
      suggested that the carotenoid pathway is more significantly influenced by other
      regulatory methods which need to be explored. It is expected that common factors
      affecting these pathways are the ones acting much before the initiation of the
      biosynthesis of respective pigments. 

PMID- 24916163
TI  - Methodology for the analysis of rare genetic variation in genome-wide association
      and re-sequencing studies of complex human traits.
AB  - Genome-wide association studies have been successful in identifying common
      variants that impact complex human traits and diseases. However, despite this
      success, the joint effects of these variants explain only a small proportion of
      the genetic variance in these phenotypes, leading to speculation that rare
      genetic variation might account for much of the 'missing heritability'.
      Consequently, there has been an exciting period of research and development into
      the methodology for the analysis of rare genetic variants, typically by
      considering their joint effects on complex traits within the same functional unit
      or genomic region. In this review, we describe a general framework for modelling
      the joint effects of rare genetic variants on complex traits in association
      studies of unrelated individuals. We summarise a range of widely used association
      tests that have been developed from this model and provide an overview of the
      relative performance of these approaches from published simulation studies. 

PMID- 24916165
TI  - Effects of iron supplementation on dominant bacterial groups in the gut, faecal
      SCFA and gut inflammation: a randomised, placebo-controlled intervention trial in
      South African children.
AB  - Fe supplementation is a common strategy to correct Fe-deficiency anaemia in
      children; however, it may modify the gut microbiota and increase the risk for
      enteropathogenic infection. In the present study, we studied the impact of Fe
      supplementation on the abundance of dominant bacterial groups in the gut, faecal
      SCFA concentration and gut inflammation in children living in rural South Africa.
      In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year
      old children with Fe deficiency received orally either tablets containing 50 mg
      Fe as FeSO4 (n 22) for 4 d/week or identical placebo (n 27). In addition, Fe
      sufficient children (n 24) were included as a non-treated reference group. Faecal
      samples were analysed at baseline and at 2, 12 and 38 weeks to determine the
      effects of Fe supplementation on ten bacterial groups in the gut (quantitative
      PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin
      concentration). At baseline, concentrations of bacterial groups in the gut,
      faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe
      sufficient children. Fe supplementation significantly improved Fe status in Fe
      deficient children and did not significantly increase faecal calprotectin
      concentration. Moreover, no significant effect of Fe treatment or time *
      treatment interaction on the concentrations of bacterial groups in the gut or
      faecal SCFA was observed compared with the placebo treatment. Also, there were no
      significant differences observed in the concentrations of any of the bacterial
      target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of
      children when correcting for baseline values. The present study suggests that in
      African children with a low enteropathogen burden, Fe status and dietary Fe
      supplementation did not significantly affect the dominant bacterial groups in the
      gut, faecal SCFA concentration or gut inflammation.

PMID- 24916166
TI  - Arsenic in drinking water and congenital heart anomalies in Hungary.
AB  - Inorganic arsenic can get easily through the placenta however there are very few
      human data on congenital anomalies related to arsenic exposure. Objective of our
      study was to explore the associations between arsenic content of drinking water
      and prevalence of some congenital anomalies. Four anomalies reported to the
      Hungarian Congenital Anomalies Registry between 1987 and 2003 were chosen to be
      analysed in relation to arsenic exposure: congenital anomalies of the circulatory
      system (n=9734) were considered as cases, while Down syndrome, club foot and
      multiple congenital malformations were used as controls (n=5880). Arsenic
      exposure of the mothers during pregnancy was estimated by using archive
      measurement data for each year and for each settlement where the mothers lived.
      Analysis of the associations between the prevalence of congenital heart anomalies
      and arsenic exposure during pregnancy was performed by logistic regression. The
      child's gender and age of the mother were adjusted for. The associations were
      evaluated by using the present EU health limit value of 10.0 MUg/L arsenic
      concentration as a cut-off point. Regular consumption of drinking water with
      arsenic concentration above 10 MUg/L during pregnancy was associated with an
      increased risk of congenital heart anomalies in general (adjusted OR=1.41; 95%
      C.I.: 1.28-1.56), and especially that of ductus Botalli persistens (adjusted
      OR=1.81, 95%C.I.: 1.54-2.11) and atrial septal defect (adjusted OR=1.79; 95%C.I.:
      1.59-2.01). The presented results showed an increased risk of congenital heart
      anomalies among infants whose mothers were exposed to drinking water with arsenic
      content above 10 MUg/L during pregnancy. Further studies of possible similar
      effects of concentrations below 10 MUg/L are warranted.

PMID- 24916167
TI  - Extracorporeal membrane oxygenation for refractory hypoxemia after liver
      transplantation in severe hepatopulmonary syndrome: a solution with pitfalls.

PMID- 24916168
TI  - Role of autologous stem cell transplantation in T-cell lymphoma patients: a
      single institution retrospective analysis.

PMID- 24916169
TI  - Asymmetric, stereodivergent synthesis of (-)-clusianone utilizing a biomimetic
      cationic cyclization.
AB  - We report a stereodivergent, asymmetric total synthesis of (-)-clusianone in six
      steps from commercial materials. We implement a challenging cationic cyclization
      forging a bond between two sterically encumbered quaternary carbon atoms.
      Mechanistic studies point to the unique ability of formic acid to mediate the
      cyclization forming the clusianone framework. 

PMID- 24916170
TI  - Diagnostic accuracy of EUS and CT of vascular invasion in pancreatic cancer: a
      systematic review.
AB  - OBJECTIVE: The objective of this study was to summarize the accuracy of
      preoperative vascular invasion with endoscopic ultrasound (EUS) and computed
      tomography (CT) test performance in pancreatic cancer with meta-analysis METHOD:
      Two reviewers searched MEDLINE database to identify relevant studies. The
      reference lists of the trials were manually searched. Included studies used
      surgical and/or histological findings as the "gold standard," and provided
      sufficient data to construct a diagnostic 2 * 2 table. A statistical program of
      Meta-Disc was used to calculate the pooled sensitivity, specificity, positive LR,
      negative LR, DOR, and the SROC curve. Publication bias was assessed by Deeks'
      asymmetry test. Sensitivity analysis and subgroup analysis were calculated to
      down the heterogeneity. Meta-regression was calculated to evaluate potential
      sources of heterogeneity RESULT: A total of 30 studies with 1,554 patients were
      included for the analysis, nine of these studies compared EUS with CT to assess
      the diagnostic efficiency The pooled sensitivity of EUS and CT was 72 % (95 % CI
      67-77 %) and 63 % (95 % CI 58-67 %), and the pooled specificity of EUS and CT was
      89 % (95 % CI 86-92 %) and 92 % (95 % CI 90-94 %), respectively. The positive LR
      of EUS and CT was 5.14 (95 % CI 3.14-8.40) and 6.21 (95 % CI 3.96-9.71), and the
      negative LR was 0.36 (95 % CI 0.25-0.52) and 0.41 (95 % CI 0.31-0.55),
      respectively. The AUCs of EUS and CT were 0.9037 and 0.8948. The subgroup
      analysis of nine studies performed both EUS and CT showed CT scan with a lower
      sensitivity of 48 % (95 % CI 0.40-0.56), when compared to EUS of 69 % (95 % CI
      0.61-0.77). The overall AUCs of CT scan appear to be lower (AUCs = 0.8589),
      compared with EUS (AUCs = 0.9379) CONCLUSION: EUS performed better than CT in
      differentiating vascular invasion preoperative on pancreatic cancer. EUS could
      provide other additional information when compared with CT.

PMID- 24916172
TI  - GC content evolution in coding regions of angiosperm genomes: a unifying
      hypothesis.
AB  - In angiosperms (as in other species), GC content varies along and between genes,
      within a genome, and between genomes of different species, but the reason for
      this distribution is still an open question. Grass genomes are particularly
      intriguing because they exhibit a strong bimodal distribution of genic GC content
      and a sharp 5'-3' decreasing GC content gradient along most genes. Here, we
      propose a unifying model to explain the main patterns of GC content variation at
      the gene and genome scale. We argue that GC content patterns could be mainly
      determined by the interactions between gene structure, recombination patterns,
      and GC-biased gene conversion. Recent studies on fine-scale recombination maps in
      angiosperms support this hypothesis and previous results also fit this model. We
      propose that our model could be used as a null hypothesis to search for
      additional forces that affect GC content in angiosperms. 

PMID- 24916171
TI  - YM155 reverses rapamycin resistance in renal cancer by decreasing survivin.
AB  - PURPOSE: Mammalian target of rapamycin inhibitor has exhibited promising
      anticancer activity for the treatment of renal cell carcinoma (RCC). However,
      many patients acquire resistance to therapeutic agents leading to treatment
      failure. The objective of this study was to determine whether treatment with
      YM155, a novel small molecule inhibitor of survivin, could reverse rapamycin
      resistance in a rapamycin-resistant RCC. METHODS: We induced a rapamycin
      resistant clear cell carcinoma cell line (Caki-1-RapR). We showed that survivin
      gene expression was significantly up-regulated in Caki-1-RapR compared with that
      in its parent cells (Caki-1). Therefore, we hypothesized that targeting of
      survivin in Caki-1-RapR could reverse the resistant phenotype in tumor cells,
      thereby enhancing the therapeutic efficacy of rapamycin. We used both in vitro
      and in vivo models to test the efficacy of YM155 either as a single agent or in
      combination with rapamycin. RESULTS: In Caki-1-RapR cells, YM155 significantly
      decreased survivin gene and protein expression levels and cell proliferation in a
      dose-dependent manner in vitro. In addition, YM155 treatment significantly
      reversed rapamycin resistance in cancer cells. In a nude mouse tumor xenograft
      model, YM155 significantly inhibited the growth of Caki-1-RapR tumor. In
      addition, YM155 significantly enhanced the antitumor effects of rapamycin in Caki
      1-RapR tumor. CONCLUSIONS: Our results suggest a potentially novel strategy to
      use YM155 to overcome the resistance in tumor cells, thereby enhancing the
      effectiveness of molecular target therapy in RCC.

PMID- 24916173
TI  - Use of home remedies: a cross-sectional survey of patients in Germany.
AB  - BACKGROUND: Reliable information regarding patient knowledge of home remedies and
      the types of health problems patients use them for is scarce. Nevertheless,
      anecdotal evidence indicates that home remedies are used by patients for managing
      minor health problems and that this can be sufficient for symptom management
      while the body recovers from minor health problems. The aim of the presented
      study was to explore patient use of home remedies in Germany. METHODS: A
      questionnaire was developed and pretested in a pilot study phase. The revised
      questionnaire was comprised of questions about general knowledge and experienced
      efficiency of home remedies, the use of home remedies for common health problems
      and socio-demographic data. Patients were recruited via randomly selected
      addresses of general practitioners (GPs) in three regions of Germany (Heidelberg,
      Erfurt and Hanover and surrounding areas). The questionnaire was handed out in
      the waiting area of GP practices. The data was analyzed descriptively. RESULTS:
      480 of 592 patients from 37 GP practices were included, according to a response
      rate of 81%. Based on the survey results, home remedies were widely known and
      used by about 80% of our respondents (on average 22 different home remedies were
      used per person). The most frequently used home remedies were steam-inhalation,
      hot lemon drink, honey, chamomile tea and chicken soup. 80% of respondents tried
      home remedies before pharmaceutical options. Information about home remedies was
      most commonly gained from family members, rather than from written guides, media
      or GPs. CONCLUSIONS: These results provide an initial overview on the use of home
      remedies from the patient's perspective in a German context. Bearing in mind the
      high use of home remedies that was reported by patients in the study, it is
      highly likely that GPs in Germany may need to advise patients on their use of
      home remedies during consultations. To this end, given the scarcity of reliable
      information on home remedies, further research is needed.

PMID- 24916174
TI  - Plasmonic enhancement in BiVO4 photonic crystals for efficient water splitting.
AB  - Photo-electrochemical water splitting is a very promising and environmentally
      friendly route for the conversion of solar energy into hydrogen. However, the
      solar-to-H2 conversion efficiency is still very low due to rapid bulk
      recombination of charge carriers. Here, a photonic nano-architecture is developed
      to improve charge carrier generation and separation by manipulating and confining
      light absorption in a visible-light-active photoanode constructed from BiVO4
      photonic crystal and plasmonic nanostructures. Synergistic effects of photonic
      crystal stop bands and plasmonic absorption are observed to operate in this
      photonic nanostructure. Within the scaffold of an inverse opal photonic crystal,
      the surface plasmon resonance is significantly enhanced by the photonic Bragg
      resonance. Nanophotonic photoanodes show AM 1.5 photocurrent densities of 3.1 +/-
      0.1 mA cm(-2) at 1.23 V versus RHE, which is among the highest for oxide-based
      photoanodes and over 4 times higher than the unstructured planar photoanode. 

PMID- 24916175
TI  - Reproducibility of results in preclinical studies: a perspective from the bone
      field.
AB  - The biomedical research enterprise-and the public support for it-is predicated on
      the belief that discoveries and the conclusions drawn from them can be trusted to
      build a body of knowledge which will be used to improve human health. As in all
      other areas of scientific inquiry, knowledge and understanding grow by layering
      new discoveries upon earlier ones. The process self-corrects and distills
      knowledge by discarding false ideas and unsubstantiated claims. Although self
      correction is inexorable in the long-term, in recent years biomedical scientists
      and the public alike have become alarmed and deeply troubled by the fact that
      many published results cannot be reproduced. The chorus of concern reached a high
      pitch with a recent commentary from the NIH Director, Francis S. Collins, and
      Principal Deputy Director, Lawrence A. Tabak, and their announcement of specific
      plans to enhance reproducibility of preclinical research that relies on animal
      models. In this invited perspective, we highlight the magnitude of the problem
      across biomedical fields and address the relevance of these concerns to the field
      of bone and mineral metabolism. We also suggest how our specialty journals, our
      scientific organizations, and our community of bone and mineral researchers can
      help to overcome this troubling trend.

PMID- 24916176
TI  - Comparison of an interactive with a didactic educational intervention for
      improving the evidence-based practice knowledge of occupational therapists in the
      public health sector in South Africa: a randomised controlled trial.
AB  - BACKGROUND: Despite efforts to identify effective interventions to implement
      evidence-based practice (EBP), uncertainty remains. Few existing studies involve
      occupational therapists or resource-constrained contexts. This study aimed to
      determine whether an interactive educational intervention (IE) was more effective
      than a didactic educational intervention (DE) in improving EBP knowledge,
      attitudes and behaviour at 12 weeks. METHODS: A matched pairs design, randomised
      controlled trial was conducted in the Western Cape of South Africa. Occupational
      therapists employed by the Department of Health were randomised using matched
      pair stratification by type (clinician or manager) and knowledge score.
      Allocation to an IE or a DE was by coin-tossing. A self-report questionnaire
      (measuring objective knowledge and subjective attitudes) and audit checklist
      (measuring objective behaviour) were completed at baseline and 12 weeks. The
      primary outcome was EBP knowledge at 12 weeks while secondary outcomes were
      attitudes and behaviour at 12 weeks. Data collection occurred at participants'
      places of employment. Audit raters were blinded, but participants and the
      provider could not be blinded. RESULTS: Twenty-one of 28 pairs reported outcomes,
      but due to incomplete data for two participants, 19 pairs were included in the
      analysis. There was a median increase of 1.0 points (95% CI = -4.0, 1.0) in the
      IE for the primary outcome (knowledge) compared with the DE, but this difference
      was not significant (P = 0.098). There were no significant differences on any of
      the attitude subscale scores. The median 12-week audit score was 8.6 points
      higher in the IE (95% CI = -7.7, 27.0) but this was not significant (P = 0.196).
      Within-group analyses showed significant increases in knowledge in both groups
      (IE: T = 4.0, P <0.001; DE: T = 12.0, P = 0.002) but no significant differences
      in attitudes or behaviour. CONCLUSIONS: The results suggest that the
      interventions had similar outcomes at 12 weeks and that the interactive component
      had little additional effect. TRIAL REGISTRATION: Pan African Controlled Trials
      Register PACTR201201000346141, registered 31 January 2012. Clinical Trials
      NCT01512823, registered 1 February 2012. South African National Clinical Trial
      Register DOH2710093067, registered 27 October 2009. The first participants were
      randomly assigned on 16 July 2008.

PMID- 24916177
TI  - First genetic analysis of Cryptosporidium from humans from Tasmania, and
      identification of a new genotype from a traveller to Bali.
AB  - Little is known about the molecular composition of Cryptosporidium species from
      humans living in the insular state of Tasmania, Australia. In the present study,
      we genetically characterized 82 samples of Cryptosporidium from humans following
      conventional coproscopic testing in a routine, diagnostic laboratory. Using a PCR
      coupled single-strand conformation polymorphism (SSCP) technique, targeting
      portions of the small subunit rRNA (SSU), and 60 kDa glycoprotein (gp60) loci, we
      identified two species of Cryptosporidium, including C. hominis (subgenotypes
      IbA10G2, IdA16, IeA12G3T3, and IfA19G1) and C. parvum (IIaA16G1R1 and IIaA18G3),
      and a new operational taxonomic unit (OTU) that genetically closely resembled C.
      wrairi. This OTU was further characterized using markers in the actin,
      Cryptosporidium oocyst wall protein (COWP), and 70 kDa heat shock protein (hsp70)
      genes. This study provides the first characterization of species and genotypes of
      Cryptosporidium from Tasmania, and presents clear genetic evidence, using five
      independent genetic loci, for a new genotype or species of Cryptosporidium in a
      Tasmanian person with a recent history of travelling to Bali, Indonesia. It would
      be interesting to undertake detailed molecular-based studies of Cryptosporidium
      in Indonesia and neighbouring countries, in conjunction with morphological and
      experimental investigations of new genotypes.

PMID- 24916179
TI  - Sub-10 nm monodisperse PbS cubes by post-synthesis shape engineering.
AB  - Sub-10 nm monodisperse PbS cubes are synthesized by reacting quasi-spherical PbS
      nanocrystals with (NH4)2S. This reaction shapes the quasi-spheres into cubes via
      preferential growth of the (111) facets. A four-band envelope function
      calculation of the energy levels accounts well for the measured absorption
      spectra. Initial studies show that PbS cubes can organize into simple square
      superlattices with short ligands. 

PMID- 24916180
TI  - Double heterozygosity for germline mutations in BRCA1 and p53 in a woman with
      early onset breast cancer.
AB  - To report on a highly unusual case of a 20-year-old woman who presented with
      multifocal metaplastic breast cancer and was subsequently found to carry
      deleterious germline mutations in both BRCA1 and p53. Genetic testing was
      requested on an expedited basis to assist in surgical decision-making and BRCA1/2
      and p53 genetic analysis was ordered concurrently. BRCA1/2 and p53 analyses were
      completed using a combination of direct DNA sequencing and multiplex ligation
      probe amplification (MLPA). The patient was found to carry a deletion of exon 3
      of the BRCA1 gene and a splice site mutation at the exon4/intron4 boundary of the
      p53 gene. To our knowledge, this is the first report of double heterozygosity in
      BRCA1 and p53. The patient's clinical presentation is highly reminiscent of that
      predicted by preclinical mouse models. In patients with early onset breast
      cancer, the possibility of germline mutations in more than one cancer
      susceptibility gene should be considered. This could have important clinical
      implications for patients and their at-risk family members.

PMID- 24916181
TI  - A class I histone deacetylase inhibitor, entinostat, enhances lapatinib efficacy
      in HER2-overexpressing breast cancer cells through FOXO3-mediated Bim1
      expression.
AB  - Although there are effective HER2-targeted agents, novel combination strategies
      in HER2-overexpressing breast cancers are needed for patients whose tumors
      develop drug resistance. To develop new therapeutic strategy, we investigated the
      combinational effect of entinostat, an oral isoform-selective histone deacetylase
      type I inhibitor, and lapatinib, a HER2/EGFR dual tyrosine kinase inhibitor, in
      HER2+ breast cancer cells. We assessed the combinational synergistic effect and
      its mechanism by CellTiter Blue assay, flow cytometry, anchorage-independent
      growth, quantitative real-time PCR, small interfering RNA, Western blotting, and
      mammary fat pad xenograft mouse models. We found that compared with entinostat or
      lapatinib alone, the two drugs in combination synergistically inhibited
      proliferation (P < 0.001), reduced in vitro colony formation (P < 0.05), and
      resulted in significant in vivo tumor shrinkage or growth inhibition in two
      xenograft mouse models (BT474 and SUM190, P < 0.001). The synergistic anti-tumor
      activity of the entinostat/lapatinib combination was due to downregulation of
      phosphorylated Akt, which activated transcriptional activity of FOXO3, resulting
      in induction of Bim1 (a BH3 domain-containing pro-apoptotic protein).
      Furthermore, entinostat sensitized trastuzumab/lapatinib-resistance-HER2
      overexpressing cells to the trastuzumab/lapatinib combination and enhanced the
      anti-proliferation effect compare with single or double combination treatment.
      This study provides evidence that entinostat has enhanced anti-tumor effect in
      combination with HER2-targeted reagent, lapatinib, and resulting in induction of
      apoptosis by FOXO3-mediated Bim1 expression. Our finding justifies for conducting
      a clinical trial of combinational treatment with entinostat, lapatinib, and
      trastuzumab in patients with HER2-overexpressing breast cancer resistant to
      trastuzumab-based treatment.

PMID- 24916182
TI  - Chaotropic-anion-induced supramolecular self-assembly of ionic polymeric
      micelles.
AB  - Traditional micelle self-assembly is driven by the association of hydrophobic
      segments of amphiphilic molecules forming distinctive core-shell nanostructures
      in water. Here we report a surprising chaotropic-anion-induced micellization of
      cationic ammonium-containing block copolymers. The resulting micelle nanoparticle
      consists of a large number of ion pairs (~60,000) in each hydrophobic core.
      Unlike chaotropic anions (e.g. ClO4(-)), kosmotropic anions (e.g. SO4(2-)) were
      not able to induce micelle formation. A positive cooperativity was observed
      during micellization, for which only a three-fold increase in ClO4(-)
      concentration was necessary for micelle formation, similar to our previously
      reported ultra-pH-responsive behavior. This unique ion-pair-containing micelle
      provides a useful model system to study the complex interplay of noncovalent
      interactions (e.g. electrostatic, van der Waals, and hydrophobic forces) during
      micelle self-assembly.

PMID- 24916183
TI  - Graphene supported plasmonic photocatalyst for hydrogen evolution in
      photocatalytic water splitting.
AB  - It is well known that the noble metal nanoparticles show active absorption in the
      visible region because of the existence of the unique feature known as surface
      plasmon resonance (SPR). Here we report the effect of plasmonic Au nanoparticles
      on the enhancement of the renewable hydrogen (H2) evolution through
      photocatalytic water splitting. The plasmonic Au/graphene/TiO2 photocatalyst was
      synthesized in two steps: first the graphene/TiO2 nanocomposites were developed
      by the hydrothermal decomposition process; then the Au was loaded by
      photodeposition. The plasmonic Au and the graphene as co-catalyst effectively
      prolong the recombination of the photogenerated charges. This plasmonic
      photocatalyst displayed enhanced photocatalytic H2 evolution for water splitting
      in the presence of methanol as a sacrificial reagent. The H2 evolution rate from
      the Au/graphene co-catalyst was about 9 times higher than that of a pure graphene
      catalyst. The optimal graphene content was found to be 1.0 wt %, giving a H2
      evolution of 1.34 mmol (i.e., 26 MUmolh(-1)), which exceeded the value of 0.56
      mmol (i.e., 112 MUmolh(-1)) observed in pure TiO2. This high photocatalytic H2
      evolution activity results from the deposition of TiO2 on graphene sheets, which
      act as an electron acceptors to efficiently separate the photogenerated charge
      carriers. However, the Au loading enhanced the H2 evolution dramatically and
      achieved a maximum value of 12 mmol (i.e., 2.4 mmolh(-1)) with optimal loading of
      2.0 wt% Au on graphene/TiO2 composites. The enhancement of H2 evolution in the
      presence of Au results from the SPR effect induced by visible light irradiation,
      which boosts the energy intensity of the trapped electron as well as active sites
      for photocatalytic activity. 

PMID- 24916184
TI  - Outcomes of laparoscopic and open restorative proctocolectomy.
AB  - BACKGROUND: The literature on laparoscopic restorative proctectomy (RP) and
      proctocolectomy (RPC) is limited. This study compared clinical outcomes of
      laparoscopic RP and RPC with those of conventional open surgery at one centre.
      METHODS: Data were analysed from consecutive patients undergoing RPC and RP
      between November 2006 and November 2011. A standard laparoscopic technique was
      developed during the first 2 years, performed by two laparoscopic surgeons, with
      selection of patients who had not previously undergone open colectomy. Study
      endpoints included postoperative length of stay, 30-day morbidity, readmission,
      reoperation, pouch function and failure. RESULTS: A total of 207 patients were
      included; open surgery was performed in 131 (63.3 per cent) and a laparoscopic
      procedure in 76 (36.7 per cent). There were no significant differences in patient
      demographics. The conversion rate was 9 per cent (7 of 76). The median (i.q.r.)
      duration of operation was shorter for open than for laparoscopic procedures: 208
      (178-255) versus 285 (255-325) min respectively (P < 0.001). Laparoscopic RPC had
      a shorter length of stay: median (i.q.r.) 6 (4-8) versus 8 (7-12) days (P <
      0.001). The rate of minor complications was lower in the laparoscopic group (33
      versus 50.4 per cent; odds ratio (OR) 0.48, 95 per cent confidence interval 0.27
      to 0.87).There were no significant differences in total complications (51 per
      cent after laparoscopy versus 61.5 per cent after open surgery; OR 0.66, 0.37 to
      1.17), anastomotic leakage, major morbidity, 30-day readmission, reoperation and
      stoma closure rates. Pouch failure (including permanent stoma) occurred in 14
      (7.7 per cent) of 181 patients. Three patients died, all in the open surgery
      group. CONCLUSION: Laparoscopic RPC is feasible with some short-term advantages.

PMID- 24916185
TI  - Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity in
      intravenous immunoglobulin as a potential therapeutic against emerging influenza
      viruses.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) is a purified pool of human
      antibodies from thousands of donors that is used to prevent or treat primary
      immune deficiency, several infectious diseases, and autoimmune diseases. The
      antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) against
      heterologous influenza strains may be present in IVIG preparations. METHODS: We
      tested 8 IVIG preparations prior to the 2009 H1N1 swine-origin influenza pandemic
      and 10 IVIG preparations made after 2010 for their ability to mediate influenza
      specific ADCC. RESULTS: ADCC mediating antibodies to A(H1N1)pdm09 hemagglutinin
      (HA) and neuraminidase (NA) were detected in IVIG preparations prior to the 2009
      H1N1 pandemic. The HA-specific ADCC targeted both the HA1 and HA2 regions of
      A(H1N1)pdm09 HA and was capable of recognizing a broad range of HA proteins
      including those from recent avian influenza strains A(H5N1) and A(H7N9). The low
      but detectable ADCC recognition of A(H7N9) was likely due to rare individuals in
      the population contributing cross-reactive antibodies to IVIG. CONCLUSIONS: IVIG
      preparations contain broadly cross-reactive ADCC mediating antibodies. IVIG may
      provide at least some level of protection for individuals at high risk of severe
      influenza disease, especially during influenza pandemics prior to the development
      of effective vaccines.

PMID- 24916186
TI  - Solid-phase library synthesis of bi-functional derivatives of oleanolic and
      maslinic acids and their cytotoxicity on three cancer cell lines.
AB  - A wide set of 264 compounds has been semisynthesized with high yields and
      purities. These compounds have been obtained through easy synthetic processes
      based on a solid-phase combinatorial methodology. All the members of this library
      have one central core of a natural pentacyclic triterpene (oleanolic or maslinic
      acid) and differ by 6 amino acids, coupled with the carboxyl group at C-28 of the
      triterpenoid skeleton, and by 10 different acyl groups attached to the hydroxyl
      groups of the A-ring of these molecules. According to the literature on the
      outstanding and promising pharmacological activities of other similar terpene
      derivatives, some of these compounds have been tested for their cytotoxic effects
      on the proliferation of three cancer cell lines: B16-F10, HT29, and Hep G2. In
      general, we have found that around 70% of the compounds tested show cytotoxicity
      in all three of the cell lines selected; around 60% of the cytotoxic compounds
      are more effective than their corresponding precursors, that is, oleanolic (OA)
      or maslinic (MA) acids; and nearly 50% of the cytotoxic derivatives have IC50
      values between 2- to 320-fold lower than their corresponding precursor (OA or
      MA). 

PMID- 24916187
TI  - An automated system for whole microscopic image acquisition and analysis.
AB  - The field of anatomic pathology has experienced major changes over the last
      decade. Virtual microscopy (VM) systems have allowed experts in pathology and
      other biomedical areas to work in a safer and more collaborative way. VMs are
      automated systems capable of digitizing microscopic samples that were
      traditionally examined one by one. The possibility of having digital copies
      reduces the risk of damaging original samples, and also makes it easier to
      distribute copies among other pathologists. This article describes the
      development of an automated high-resolution whole slide imaging (WSI) system
      tailored to the needs and problems encountered in digital imaging for pathology,
      from hardware control to the full digitization of samples. The system has been
      built with an additional digital monochromatic camera together with the color
      camera by default and LED transmitted illumination (RGB). Monochrome cameras are
      the preferred method of acquisition for fluorescence microscopy. The system is
      able to digitize correctly and form large high resolution microscope images for
      both brightfield and fluorescence. The quality of the digital images has been
      quantified using three metrics based on sharpness, contrast and focus. It has
      been proved on 150 tissue samples of brain autopsies, prostate biopsies and lung
      cytologies, at five magnifications: 2.5*, 10*, 20*, 40*, and 63*. The article is
      focused on the hardware set-up and the acquisition software, although results of
      the implemented image processing techniques included in the software and applied
      to the different tissue samples are also presented.

PMID- 24916188
TI  - 3-Dimensional atomic scale structure of the ionic liquid-graphite interface
      elucidated by AM-AFM and quantum chemical simulations.
AB  - In situ amplitude modulated atomic force microscopy (AM-AFM) and quantum chemical
      simulations are used to resolve the structure of the highly ordered pyrolytic
      graphite (HOPG)-bulk propylammonium nitrate (PAN) interface with resolution
      comparable with that achieved for frozen ionic liquid (IL) monolayers using STM.
      This is the first time that (a) molecular resolution images of bulk IL-solid
      interfaces have been achieved, (b) the lateral structure of the IL graphite
      interface has been imaged for any IL, (c) AM-AFM has elucidated molecular level
      structure immersed in a viscous liquid and (d) it has been demonstrated that the
      IL structure at solid surfaces is a consequence of both thermodynamic and kinetic
      effects. The lateral structure of the PAN-graphite interface is highly ordered
      and consists of remarkably well-defined domains of a rhomboidal superstructure
      composed of propylammonium cations preferentially aligned along two of the three
      directions in the underlying graphite lattice. The nanostructure is primarily
      determined by the cation. Van der Waals interactions between the propylammonium
      chains and the surface mean that the cation is enriched in the surface layer, and
      is much less mobile than the anion. The presence of a heterogeneous lateral
      structure at an ionic liquid-solid interface has wide ranging ramifications for
      ionic liquid applications, including lubrication, capacitive charge storage and
      electrodeposition. 

PMID- 24916189
TI  - Entropy-based selection for maternal-fetal genotype incompatibility with
      application to preterm prelabor rupture of membranes.
AB  - BACKGROUND: Maternal-fetal genotype incompatibility (MFGI) is increasingly
      reported to influence human diseases, especially pregnancy-related complications.
      In practice, it is challenging to identify the ideal incompatibility model for
      analysis, since the true MFGI mechanism is generally unknown. The underlying MFGI
      mechanism for different genetic variants can vary, and to use a single
      incompatibility model for all circumstances would cause power loss in testing
      MFGI. RESULTS: In this article, we propose a practical 2-step procedure that
      incorporates a model selection strategy based on an entropy measurement to select
      the most appropriate MFGI model represented by data and test the significance of
      the MFGI effect using the chosen model within the generalized linear regression
      framework. CONCLUSIONS: Our simulation studies show that the proposed two-step
      procedure controls the type I error rate and increase the testing power under
      various scenarios. In a real data application, our analysis reveals genes having
      an MFGI effect, which may not be detected with a non-model selection counterpart.

PMID- 24916190
TI  - The prevalence of schizophrenia in mainland China: evidence from epidemiological
      surveys.
AB  - OBJECTIVE: Schizophrenia is a severe mental disorder. Its prevalence appears
      inconsistent in different regions of China; thus, we conducted this meta-analysis
      to estimate the prevalence of schizophrenia in mainland China. METHOD: Studies on
      the prevalence of schizophrenia in mainland China were identified from electronic
      databases up to July 2013. Meta-analysis was used for prevalence of schizophrenia
      estimate. RESULTS: For lifetime prevalence of schizophrenia, prevalence of 5.44
      per 1000 (overall), 5.33 per 1000 (males), 5.51 per 1000 (females), 6.60 per 1000
      (urban) and 4.73 per 1000 (rural) were estimated; there was no significant
      difference between males and females, while prevalence for urban dwellers was
      higher than for rural (OR=1.44, 95%CI: 1.30-1.59). For point prevalence of
      schizophrenia, prevalence of 4.62 per 1000 (overall), 4.63 per 1000 (males), 4.95
      per 1000 (females), 5.15 per 1000 (urban) and 4.44 per 1000 (rural) were
      estimated; no statistical difference was found in males and females, but
      prevalence for urban dwellers was higher than for rural (OR=1.20; 95%CI: 1.02
      1.41). CONCLUSION: The prevalence estimate results were consistent with the
      international prevalence estimate of schizophrenia in mainland China. There was
      no significant difference between males and females, while prevalence for urban
      dwellers was higher than for rural.

PMID- 24916191
TI  - How much salt do adults consume in climate vulnerable coastal Bangladesh?
AB  - BACKGROUND: Evidence from numerous studies suggests that salt intake is an
      important determinant of elevated blood pressure. Robust data about salt
      consumption among adults in Bangladesh is sparse. However, much evidence suggests
      saline intrusion due to sea level rise as a result of climate change exposes more
      than 20 million people to adverse effects of salinity through the food and water
      supply. The objective of our study was to assess salt consumption among adults in
      a coastal region of Bangladesh. METHODS: Our study was cross sectional and
      conducted during October-November 2011. A single 24 hour urine was collected from
      400 randomly selected individuals over 18 years of age from Chakaria, a rural,
      coastal area in Southeastern Bangladesh. Logistic regression was conducted to
      identify the determinants of high salt consumption. RESULTS: The mean urinary
      sodium excretion was 115 mmol/d (6.8 g salt). Based on logistic regression using
      two different cutoff points (IOM and WHO), housewives and those living in the
      coastal area had a significantly higher probability of high salt intake compared
      with people who were engaged in labour-intensive occupations and who lived in
      hilly areas. CONCLUSION: It is important to create awareness about the
      implication of excessive salt intake on health and to develop strategies for
      reducing salt intake that can be implemented at the community-level. A
      sustainable policy for salt reduction in the Bangladeshi diet should be
      formulated with special emphasis on coastal areas.

PMID- 24916192
TI  - Recapitulating endochondral ossification: a promising route to in vivo bone
      regeneration.
AB  - Despite its natural healing potential, bone is unable to regenerate sufficient
      tissue within critical-sized defects, resulting in a non-union of bone ends. As a
      consequence, interventions are required to replace missing, damaged or diseased
      bone. Bone grafts have been widely employed for the repair of such critical-sized
      defects. However, the well-documented drawbacks associated with autografts,
      allografts and xenografts have motivated the development of alternative treatment
      options. Traditional tissue engineering strategies have typically attempted to
      direct in vitro bone-like matrix formation within scaffolds prior to implantation
      into bone defects, mimicking the embryological process of intramembranous
      ossification (IMO). Tissue-engineered constructs developed using this approach
      often fail once implanted, due to poor perfusion, leading to avascular necrosis
      and core degradation. As a result of such drawbacks, an alternative tissue
      engineering strategy, based on endochondral ossification (ECO), has begun to
      emerge, involving the use of in vitro tissue-engineered cartilage as a transient
      biomimetic template to facilitate bone formation within large defects. This is
      driven by the hypothesis that hypertrophic chondrocytes can secrete angiogenic
      and osteogenic factors, which play pivotal roles in both the vascularization of
      constructs in vivo and the deposition of a mineralized extracellular matrix, with
      resulting bone deposition. In this context, this review focuses on current
      strategies taken to recapitulate ECO, using a range of distinct cells,
      biomaterials and biochemical stimuli, in order to facilitate in vivo bone
      formation.

PMID- 24916193
TI  - Physical characterisation and long-term stability studies on quaternary ammonium
      palmitoyl glycol chitosan (GCPQ)--a new drug delivery polymer.
AB  - N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ)
      is a self-assembling polymer, which enables the oral bioavailability of peptide
      and hydrophobic drugs. In preparation for clinical testing, here we examine
      GCPQ's synthesis reproducibility, pKa, thermal, and rheological properties. GCPQ
      was synthesised by acid degradation of glycol chitosan (GC), reaction with
      palmitic acid N-hydroxysuccinimide (PNS) and methylation. A GC monomer, PNS molar
      feed ratio of 0.92 together with a gravimetric feed ratio for N-palmitoyl-6-O
      glycolchitosan, methyl iodide of 3.3, reproducibly produces GCPQ48 (Mw = 19.9 +/-
      9.9 kDa, Mn = 13.1 +/- 2.4 kDa, mol % palmitoylation = 23 +/- 2.7, mol %
      quaternisation = 10 +/- 0.23, n = 56). GCPQ48 decomposes at 218 +/- 4.3  degrees
      C, is glassy at room temperature (Tg = 164.4 +/- 8.5  degrees C), is a weak base
      (pKa = 5.99 +/- 0.15), and produces micellar dispersions at neutral pH. Below a
      concentration of 0.07 g mL(-1) , GCPQ48 dispersions showed Newtonian rheological
      behaviour but at higher concentrations, the polymer undergoes shear thinning
      because of the chain disentanglement at high shear rates. GCPQ48 forms a network
      of micelles and concentrated (0.09 g mL(-1) ) dispersions are viscoelastic, with
      the storage modulus exceeding the loss modulus at high frequencies. Solid GCPQ48
      was stable when stored at room temperature for 18 months.

PMID- 24916194
TI  - Whatever happened to the 'mad, bad' scientist? Overturning the stereotype.
AB  - The cluster of myths relating to the pursuit of knowledge has perpetuated the
      archetype of the alchemist/scientist as sinister, dangerous, possibly mad and
      threatening to society's values. Shelley's Frankenstein provided imagery and a
      vocabulary universally invoked in relation to scientific discoveries and
      technological innovation. The reasons for the longevity of this seemingly
      antiquated, semiotic imagery are discussed. In the twenty-first century, this
      stereotype has been radically revised, even overturned. Scientists are now rarely
      objects of fear or mockery. Mathematicians, both real-life and fictional, are
      discussed here as being representative of scientists now depicted empathically.
      This article examines possible sociological reasons for this reversal; what the
      revisionist image suggests about society's changed attitudes to science; and what
      might be the substitute fears and sources of horror. 

PMID- 24916195
TI  - Cinematic climate change, a promising perspective on climate change
      communication.
AB  - Previous research findings display that after having seen popular climate change
      films, people became more concerned, more motivated and more aware of climate
      change, but changes in behaviors were short-term. This article performs a meta
      analysis of three popular climate change films, The Day after Tomorrow (2005), An
      Inconvenient Truth (2006), and The Age of Stupid (2009), drawing on research in
      social psychology, human agency, and media effect theory in order to formulate a
      rationale about how mass media communication shapes our everyday life experience.
      This article highlights the factors with which science blends in the reception of
      the three climate change films and expands the range of options considered in
      order to encourage people to engage in climate change mitigation actions. 

PMID- 24916196
TI  - Retention of the original LLC structure in a cross-linked poly(ethylene glycol)
      diacrylate hydrogel with reinforcement from a silica network.
AB  - Cross-linked poly(ethylene glycol) diacrylate (PEGDA) hydrogels with uniformly
      controlled nanoporous structures templated from hexagonal lyotropic liquid
      crystals (LLC) represent separation membrane materials with potentially high
      permeability and selectivity due to their high pore density and narrow pore size
      distribution. However, retaining LLC templated nanostructures is a challenge as
      the polymer gels are not strong enough to sustain the surface tension during the
      drying process. In the current study, cross-linked PEGDA gels were reinforced
      with a silica network synthesized via an in situ sol-gel method, which assists in
      the retention of the hexagonal LLC structure. The silica precursor does not
      obstruct the formation of hexagonal phases. After surfactant removal and drying,
      these hexagonal structures in samples with a certain amount of tetraethoxysilane
      (TEOS) loading are well retained while the nanostructures are collapsed in
      samples without silica reinforcement, leading to the hypothesis that the
      reinforcement provided by the silica network stabilizes the LLC structure. The
      study examines the conditions necessary for a sufficient and well dispersed
      silica network in PEGDA gels that contributes to the retention of original LLC
      structures, which potentially enables broad applications of these gels as
      biomedical and membrane materials. 

PMID- 24916197
TI  - The provision of spiritual and pastoral care following stillbirth in Ireland: a
      mixed methods study.
AB  - BACKGROUND: The death of a baby is recognised as one of the most difficult
      bereavements with life-long impact for parents. How bereaved parents are cared
      for influences their grief journey. Optimal holistic care is provided when the
      physical, emotional, spiritual and social needs of parents are attended to. This
      study reviewed how spiritual care is provided to bereaved parents following
      stillbirth in maternity units in Ireland and the impact of stillbirth on
      healthcare chaplains. METHODS: This was a mixed methods study using
      semistructured qualitative interviews with hospital chaplains in Irish maternity
      units. Quantitative data about the provision of services to bereaved parents were
      collated from the interviews. Qualitative data were analysed thematically to
      identify key themes. RESULTS: 20 chaplains from 17 units participated in the
      study (85% of Irish maternity units). 12 chaplains (60%) are formally accredited
      chaplains; only one has received specialist training in perinatal bereavement
      care. 11 chaplains (55%) provide follow-up bereavement care. Seven chaplains
      (35%) did not feel part of the multidisciplinary team. The main themes that
      emerged were the impact of stillbirth, suffering and the challenge to faith
      creating inner conflict and doubt. CONCLUSIONS: The provision of spiritual care
      following stillbirth in Ireland is diverse. Spiritual care in this specialised
      area by chaplains who are not professionally trained and accredited potentially
      impacts quality and depth of care. Chaplains experience considerable impact and
      challenge to personal faith and belief as they provide care. Recommendations are
      made for ongoing education and greater support for chaplains.

PMID- 24916198
TI  - Knowledge of and attitudes towards palliative care and hospice services among
      patients with advanced chronic kidney disease.
AB  - OBJECTIVES: Palliative care is greatly underutilised for patients dying from
      advanced chronic kidney disease (CKD). This study explored CKD patients'
      knowledge of, and attitudes to, palliative and hospice care. DESIGN AND
      INTERVENTION: This was a cross-sectional interview-based survey of stage 5 CKD
      patients. SETTING: Both dialysis patients and those managed without dialysis were
      assessed in a university-based renal programme in Alberta, Canada. OUTCOME
      MEASURES: The primary outcome was validated patient knowledge of, and attitudes,
      towards palliative and hospice care. Secondary analyses of associations between
      knowledge and potential explanatory variables such as patient demographics,
      living circumstances, self-assigned ethnicity, socioeconomic position and sources
      of knowledge were explored. RESULTS: Only 22.2% and 17.9% of 436 patients
      surveyed possessed a correct understanding of palliative and hospice care,
      respectively, and perceptions were mostly negative. Sources of knowledge of these
      services rarely involved healthcare professionals (3.1%-7.7%). Multivariable
      analysis identified that white participants were more than 12 times more likely
      to have accurate knowledge than non-Caucasian patients, not accounted for by
      socioeconomic position. Accurate knowledge was also more likely among patients
      who had personal experience with palliative care, or obtained their knowledge
      firsthand from family and friends. After palliative and hospice care were
      described, the vast majority of patients felt these services were valuable and
      should be offered to patients with advanced CKD (87.8% and 89.7%, respectively).
      CONCLUSIONS: Based on study findings, CKD patient and family education about the
      benefits of palliative and hospice services is likely important in optimal use of
      these services.

PMID- 24916199
TI  - Does fusion status after posterior lumbar interbody fusion affect patient-based
      QOL outcomes? An evaluation performed using a patient-based outcome measure.
AB  - BACKGROUND: Although delayed union or pseudoarthrosis after lumbar arthrodesis
      has been recognized as a major radiographic complication, little has been known
      about the effect of fusion status on the patient's quality-of-life (QOL) outcome.
      The purpose of this study was to investigate the effects of fusion status after
      posterior lumbar interbody fusion (PLIF) on QOL outcomes by using the Japanese
      Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). METHODS:
      Among 100 patients who underwent single level PLIF for spinal canal stenosis, 29
      who had not achieved fusion (incomplete fusion group) and 29 age- and sex ratio
      matched patients who had achieved fusion (fusion group) 6 months after surgery
      were enrolled. Overall clinical evaluation was performed before and 6 months
      after surgery: the physician determined the Japanese Orthopaedic Association
      Score for Low Back Pain (JOA score); the JOABPEQ and visual analogue scale (VAS)
      values were collected. The recovery rate of the JOA score, changes in all JOABPEQ
      subdomain scores and in the VAS values were calculated. All variables were
      compared between the groups. RESULTS: The preoperative JOA scores, JOABPEQ scores
      of all subdomains, and VAS values of all categories did not differ between the
      groups. The recovery rate was higher in the fusion group than the incomplete
      fusion group (p = 0.0185). The changes in the JOABPEQ scores for walking ability
      and social life function were significantly greater in the fusion group than the
      incomplete fusion group (walking ability, p = 0.0172; social life function, p =
      0.0191). The postoperative VAS values and changes in the VAS values for all
      categories did not differ between the groups. CONCLUSIONS: Incomplete fusion
      after PLIF correlated with poor improvement in walking ability and social life
      function. Therefore, the achievement of fusion after PLIF is essential to obtain
      better patient QOL outcomes.

PMID- 24916200
TI  - Rhodium-catalyzed B-H activation of 1,2-azaborines: synthesis and
      characterization of BN isosteres of stilbenes.
AB  - The first example of catalytic B-H activation of azaborines leading to a new
      family of stilbene derivatives through dehydrogenative borylation is reported.
      Ten 1,2-azaborine-based BN isosteres of stilbenes have been synthesized using
      this method, including a BN isostere of a biologically active stilbene. It is
      demonstrated that BN/CC isosterism in the context of stilbenes can lead to
      significant changes in the observed photophysical properties such as higher
      quantum yield and a larger Stokes shift. Direct comparative analysis of BN
      stilbene 3g and its carbonaceous counterpart 6g is consistent with a stronger
      charge-transfer character of the excited state exhibited by 3g in which the 1,2
      azaborine heterocycle serves as a better electron donor than the corresponding
      arene. 

PMID- 24916201
TI  - A 3D insight on the catalytic nanostructuration of few-layer graphene.
AB  - The catalytic cutting of few-layer graphene is nowadays a hot topic in materials
      research due to its potential applications in the catalysis field and the
      graphene nanoribbons fabrication. We show here a 3D analysis of the
      nanostructuration of few-layer graphene by iron-based nanoparticles under
      hydrogen flow. The nanoparticles located at the edges or attached to the steps on
      the FLG sheets create trenches and tunnels with orientations, lengths and
      morphologies defined by the crystallography and the topography of the carbon
      substrate. The cross-sectional analysis of the 3D volumes highlights the role of
      the active nanoparticle identity on the trench size and shape, with emphasis on
      the topographical stability of the basal planes within the resulting trenches and
      channels, no matter the obstacle encountered. The actual study gives a deep
      insight on the impact of nanoparticles morphology and support topography on the
      3D character of nanostructures built up by catalytic cutting. 

PMID- 24916202
TI  - Metal-containing residues from industry and in the environment:
      geobiotechnological urban mining.
AB  - This chapter explains the manifold geobiotechnological possibilities to separate
      industrial valuable metals from various industrial residues and stored waste
      products of the past. In addition to an overview of the different microbially
      catalyzed chemical reactions applicable for a separation of metals and details of
      published studies, results of many individual investigations from various
      research projects are described. These concern the separation of rare earth
      elements from phosphorous production slags, the attempts of tin leaching from
      mining flotation residues, the separation of metals from spent catalysts, or the
      treatment of ashes as valuable metal-containing material. The residues of
      environmental technologies are integrated into this overview as well. The
      description of the different known microbial processes offers starting points for
      suitable and new technologies. In addition to the application of
      chemolithoautotrophic microorganisms the use of heterotrophic microorganisms is
      explained. 

PMID- 24916204
TI  - Pulmonary function differences in patients with chronic right heart failure
      secondary to pulmonary arterial hypertension and chronic left heart failure.
AB  - BACKGROUND: Pulmonary abnormalities are found in both chronic heart failure (CHF)
      and pulmonary arterial hypertension (PAH). The differences of pulmonary function
      in chronic left heart failure and chronic right heart failure are not fully
      understood. MATERIAL AND METHODS: We evaluated 120 patients with stable CHF (60
      with chronic left heart failure and 60 with chronic right heart failure). All
      patients had pulmonary function testing, including pulmonary function testing at
      rest and incremental cardiopulmonary exercise testing (CPX). RESULTS: Patients
      with right heart failure had a significantly lower end-tidal partial pressure of
      CO2 (PetCO2), higher end-tidal partial pressure of O2 (PetO2) and minute
      ventilation/CO2 production (VE/VCO2) at rest. Patients with right heart failure
      had a lower peak PetCO2, and a higher peak dead space volume/tidal volume (VD/VT)
      ratio, peak PetO2, peak VE/VCO2, and VE/VCO2 slope during exercise. Patients with
      right heart failure had more changes in ?PetCO2 and ?VE/VCO2, from rest to
      exercise. CONCLUSIONS: Patients with right heart failure had worse pulmonary
      function at rest and exercise, which was due to severe ventilation/perfusion
      (V/Q) mismatching, severe ventilation inefficiency, and gas exchange abnormality.

PMID- 24916205
TI  - Characteristics of two calcium pectinates prepared from citrus pectin using
      either calcium chloride or calcium hydroxide.
AB  - Calcium pectinate (CaP) was prepared from citrus pectin using either calcium
      chloride (C-CaP) or calcium hydroxide (HO-CaP) as the source of calcium for the
      reaction. The production yields and the rates of decalcification for the two
      calcium pectinates were compared and both found to be lower for C-CaP than for HO
      CaP. In an attempt to explain these differences, certain chemical and structural
      characteristics of the two products, including functional groups (-CH3, C?O, COO
      ), rheological properties, morphology, and egg-box junction zones, were
      investigated by Fourier transformation infrared (FTIR) spectroscopy, rheology,
      scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results from
      FTIR showed that, with an increase in calcium content, the wavenumber values and
      peak areas of FTIR for -CH3, C?O, and COO- groups all changed dramatically for C
      CaP, while they were virtually unchanged for HO-CaP. Rheological analysis of the
      CaP gel showed that C-CaP had a stronger cross-linked network structure and a
      greater range of elastic behavior as compared to HO-CaP. SEM images of two CaP
      gels showed irregular membranes. C-CaP maintained a tight structure and a smooth
      surface, whereas HO-CaP was loose and rough. The results from XRD revealed a
      higher degree of crystallinity within C-CaP than within HO-CaP, which indicated
      that C-CaP possessed compact, ordered, and stable egg-box junction zones while
      the junction zones in HO-CaP were metastable and loose. 

PMID- 24916203
TI  - Combined identification of septal flash and absence of myocardial scar by cardiac
      magnetic resonance imaging improves prediction of response to cardiac
      resynchronization therapy.
AB  - BACKGROUND AND AIMS OF STUDY: Septal flash (SF) describes early inward motion of
      the ventricular septum in patients with left bundle branch block (LBBB), and
      correction corresponds to increased response to cardiac resynchronization therapy
      (CRT). SF has traditionally been assessed by echocardiography. We sought to
      determine if cardiac magnetic resonance (CMR) imaging could identify SF and if
      the additional assessment of scar would improve the ability of CMR to predict CRT
      response. METHODS: Fifty-two patients with LBBB and heart failure underwent
      prospective CMR scanning prior to CRT implantation. The presence of SF was
      assessed visually and by using endocardial contour-tracking software. Presence
      and extent of myocardial scar was assessed by delayed enhancement imaging during
      CMR. The association between SF, scar and reverse remodelling (RR) at 6 months
      was explored. RESULTS: RR rate to CRT at 6 months was 52%. CMR-derived SF was
      identified in 24 (46%) patients. RR was seen in more patients with SF than those
      without (88% vs 21%; P < 0.001). The absence of scar combined with the presence
      of SF had 96% specificity for predicting RR. In a multivariate regression model,
      the presence of SF was the only independent predictor of RR. CONCLUSION: SF can
      be assessed by CMR and predicts increased response to CRT. The additional value
      of CMR is the assessment of scar. The presence of SF with no scar is a highly
      specific predictor of CRT response.

PMID- 24916206
TI  - Breastfeeding versus formula-feeding and girls' pubertal development.
AB  - To examine the association of breastfeeding or its duration with timing of girls'
      pubertal onset, and the role of BMI as a mediator in these associations. A
      population of 1,237 socio-economically and ethnically diverse girls, ages 6-8
      years, was recruited across three geographic locations (New York City,
      Cincinnati, and the San Francisco Bay Area) in a prospective study of predictors
      of pubertal maturation. Breastfeeding practices were assessed using self
      administered questionnaire/interview with the primary caregiver. Girls were seen
      on at least annual basis to assess breast and pubic hair development. The
      association of breastfeeding with pubertal timing was estimated using parametric
      survival analysis while adjusting for body mass index, ethnicity, birth-weight,
      mother's education, mother's menarcheal age, and family income. Compared to
      formula fed girls, those who were mixed-fed or predominantly breastfed showed
      later onset of breast development [hazard ratios 0.90 (95 % CI 0.75, 1.09) and
      0.74 (95 % CI 0.59, 0.94), respectively]. Duration of breastfeeding was also
      directly associated with age at onset of breast development (p trend = 0.008).
      Associations between breastfeeding and pubic hair onset were not significant. In
      stratified analysis, the association of breastfeeding and later breast onset was
      seen in Cincinnati girls only. The association between breast feeding and
      pubertal onset varied by study site. More research is needed about the
      environments within which breastfeeding takes place in order to better understand
      whether infant feeding practices are a potentially modifiable risk factor that
      may influence age at onset of breast development and subsequent risk for disease
      in adulthood.

PMID- 24916207
TI  - Use of job aids to improve facility-based postnatal counseling and care in rural
      Benin.
AB  - This study examined the effect of a job aids-focused intervention on quality of
      facility-based postnatal counseling, and whether increased communication improved
      in-hospital newborn care and maternal knowledge of home practices and danger
      signs requiring urgent care. Ensuring mothers and newborns receive essential
      postnatal services, including health counseling, is integral to their survival.
      Yet, quality of clinic-based postnatal services is often low, and evidence on
      effective improvement strategies is scarce. Using a pre-post randomized design,
      data were drawn from direct observations and interviews with 411 mother-newborn
      pairs. Multi-level regression models with difference-in-differences analyses
      estimated the intervention's relative effect, adjusting for changes in the
      comparison arm. The mean percent of recommended messages provided to recently
      delivered women significantly improved in the intervention arm as compared to the
      control (difference-in-differences [?i - ?c] +30.9, 95 % confidence interval (CI)
      19.3, 42.5), and the proportion of newborns thermally protected within the first
      hour (?i - ?c +33.7, 95 % CI 19.0, 48.4) and delayed for bathing (?i - ?c +23.9,
      95 % CI 9.4, 38.4) significantly increased. No significant changes were observed
      in early breastfeeding (?i - ?c +6.8, 95 % CI -2.8, 16.4) which was nearly
      universal. Omitting traditional umbilical cord substances rose slightly, but was
      insignificant (?i - ?c +8.5, 95 % CI -2.8, 19.9). The proportion of mothers with
      correct knowledge of maternal (?i - ?c +27.8, 95 % CI 11.0, 44.6) and newborn (?i
      - ?c +40.3, 95 % CI 22.2, 58.4) danger signs grew substantially, as did awareness
      of several home-care practices (?i - ?c +26.0, 95 % CI 7.7, 44.3). Counseling job
      aids can improve the quality of postnatal services. However, achieving reduction
      goals in maternal and neonatal mortality will likely require more comprehensive
      approaches to link enhanced facility services with community-based initiatives.

PMID- 24916208
TI  - Development of a clinical registry-based 30-day readmission measure for coronary
      artery bypass grafting surgery.
AB  - BACKGROUND: Reducing readmissions is a major healthcare reform goal, and
      reimbursement penalties are imposed for higher-than-expected readmission rates.
      Most readmission risk models and performance measures are based on administrative
      rather than clinical data. METHODS AND RESULTS: We examined rates and predictors
      of 30-day all-cause readmission following coronary artery bypass grafting surgery
      by using nationally representative clinical data (2008-2010) from the Society of
      Thoracic Surgeons National Database linked to Medicare claims records. Among 265
      434 eligible Medicare records, 226 960 (86%) were successfully linked to Society
      of Thoracic Surgeons records; 162 572 (61%) isolated coronary artery bypass
      grafting admissions constituted the study cohort. Logistic regression was used to
      identify readmission risk factors; hierarchical regression models were then
      estimated. Risk-standardized readmission rates ranged from 12.6% to 23.6%
      (median, 16.8%) among 846 US hospitals with >=30 eligible cases and >=90% of
      eligible Centers for Medicare and Medicaid Services records linked to the Society
      of Thoracic Surgeons database. Readmission predictors (odds ratios [95%
      confidence interval]) included dialysis (2.02 [1.87-2.19]), severe chronic lung
      disease (1.58 [1.49-1.68]), creatinine (2.5 versus 1.0 or lower:1.49 [1.41-1.57];
      2.0 versus 1.0 or lower: 1.37 [1.32-1.43]), insulin-dependent diabetes mellitus
      (1.45 [1.39-1.51]), obesity in women (body surface area 2.2 versus 1.8: 1.44
      [1.35-1.53]), female sex (1.38 [1.33-1.43]), immunosuppression (1.38 [1.28
      1.49]), preoperative atrial fibrillation (1.36 [1.30-1.42]), age per 10-year
      increase (1.36 [1.33-1.39]), recent myocardial infarction (1.24 [1.08-1.42]), and
      low body surface area in men (1.22 [1.14-1.30]). C-statistic was 0.648. Fifty-two
      hospitals (6.1%) had readmission rates statistically better or worse than
      expected. CONCLUSIONS: A coronary artery bypass grafting surgery readmission
      measure suitable for public reporting was developed by using the national Society
      of Thoracic Surgeons clinical data linked to Medicare readmission claims.

PMID- 24916209
TI  - Effect of bilateral internal mammary artery grafts on long-term survival: a meta
      analysis approach.
AB  - BACKGROUND: Although the potential survival benefit of bilateral internal mammary
      artery (BIMA) grafting in comparison with single internal mammary artery (SIMA)
      grafting has been emphasized by many investigators, the use of BIMA is still low
      in clinical practice in the absence of randomized trials and long-term results.
      In the current study, we aimed to assess if there is a long-term survival benefit
      of BIMA up to 10 years after coronary bypass surgery. METHODS AND RESULTS: We
      selected published articles comparing survival between SIMA and BIMA patients
      with follow-up duration of more than a mean of 9 years. We evaluated the log
      hazard ratio with 95% confidence interval for included studies by using a random
      effects meta-analysis. Nine eligible observational studies provided 15 583
      patients (8270 SIMA and 7313 BIMA) for meta-analysis. Five studies used
      propensity score methods for statistical adjustment, 2 with a propensity score
      based patient-matching method and 3 with quintile-based stratification. A
      significant reduction in mortality by using BIMA was observed (hazard ratio,
      0.79; 95% confidence interval, 0.75-0.84); no study showed any significantly
      harmful effect of BIMA on survival. Subgroups of studies using different
      statistical approaches-unmatched, quintile-based propensity score analysis, and
      propensity score-based exact patient matching-all showed the survival benefit of
      BIMA grafting. CONCLUSIONS: BIMA grafting appears to have better survival with up
      to 10 years follow-up in comparison with SIMA grafting. Long-term survival
      benefit of BIMA seems to continue in the second decade after surgery. An ongoing
      randomized trial comparing SIMA and BIMA groups will add evidence on this issue.

PMID- 24916210
TI  - Response of hydroponically grown head lettuce on residual monomer from
      polyacrylamide.
AB  - The aim was to assess acrylamide monomer (AMD) uptake by hydroponically grown
      lettuce. Lettuce was cultivated by applying plant tissue testing in a recycled
      system by the use of nutrient solutions prepared with two water-soluble
      flocculants F3 and F4 containing 176 and 763 mg kg(-1) of AMD, respectively. The
      effects on growth, fresh weight and plant leaf quality were evaluated by
      comparing these treatments and one control standard nutrient solution typically
      recommended for lettuce hydroponic cultivation. To assess the nutritional status
      of lettuce, samples were collected and lyophilised before determination of the
      selected micro- and macro-element contents. An HPLC with photodiode array
      detector method was applied to determine AMD in both selected flocculants and
      dried plant samples. Results show that lettuces cultivated under the conditions
      described above absorb AMD from nutrient solutions into their leaves. The AMD
      presence in recycled nutrient solutions has a negative influence on the growth of
      lettuce, reducing their average fresh weight and average number of leaves. The
      study confirmed that the problem of AMD mobility and its accumulation risk in
      plants should to be an important topic with respect to safe polyacrylamide (PAM)
      handling in the agro food area. 

PMID- 24916211
TI  - Cutaneous lichen planus: A systematic review of treatments.
AB  - Various treatment modalities are available for cutaneous lichen planus. Pubmed,
      EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of
      Controlled Trials, Database of Abstracts of Reviews of Effects, and Health
      Technology Assessment Database were searched for all the systematic reviews and
      randomized controlled trials related to cutaneous lichen planus. Two systematic
      reviews and nine relevant randomized controlled trials were identified.
      Acitretin, griseofulvin, hydroxychloroquine and narrow band ultraviolet B are
      demonstrated to be effective in the treatment of cutaneous lichen planus.
      Sulfasalazine is effective, but has an unfavorable safety profile. KH1060, a
      vitamin D analogue, is not beneficial in the management of cutaneous lichen
      planus. Evidence from large scale randomized trials demonstrating the safety and
      efficacy for many other treatment modalities used to treat cutaneous lichen
      planus is simply not available. 

PMID- 24916212
TI  - The effect of 4% sodium cromoglicate cutaneous emulsion compared to vehicle in
      atopic dermatitis in children--A meta-analysis of total SCORAD scores.
AB  - An emulsion containing 4% sodium cromoglicate (4% SCG emulsion) has been
      developed for the treatment of atopic dermatitis in children. We have conducted a
      meta-analysis of the primary outcome measure (the change in SCORAD score) used in
      randomized clinical trials (RCTs) with this product. We conducted a search of
      standard using the keywords, sodium cromoglicate, cromolyn sodium, topical,
      atopic dermatitis, clinical trial. We identified 19 clinical studies of which 3
      used this 4% SCG emulsion formulation, one was a RCT using the change in SCORAD
      score. We were given access to two further unpublished RCTs, with this measure.
      The RCTs included 490 subjects (mean age 5.3 years). Each RCT was multicentre of
      12 weeks duration, comparing 4% SCG emulsion with the vehicle in which the SCG
      was dissolved. Using study as the unit and the fixed effect model, the mean
      difference (95% CI) in the change in SCORAD score was -2.82 (-5.36; -0.29), p =
      0.03. Using centre as the unit, and the fixed effect model, the mean difference
      (95% CI) in the change in SCORAD score was -2.82 (-5.82; -0.46), p = 0.02. These
      results support the efficacy of this new topical treatment in children with
      atopic dermatitis. 

PMID- 24916213
TI  - Political inaction brings spectre of spiralling fees.
AB  - The Queen's Speech might look like a throwback to olden times, but buried beneath
      the pomp are important announcements that set the parliamentary agenda for the
      year ahead. For nurses, last week's ceremony was highly significant for something
      Her Majesty did not say, which will have far-reaching consequences for everyone
      on the Nursing and Midwifery Council register. 

PMID- 24916214
TI  - Protesters take to the streets in call for reversal of pay freeze 'insult'.
AB  - Nurses across England have united in public protest at the government's refusal
      to give all NHS workers a 1 per cent pay rise this year. 

PMID- 24916215
TI  - Performance pay guidance issued by employer body.
AB  - NHS organisations would cut their wage bill if they introduced systems linking
      staff performance with incremental pay. 

PMID- 24916216
TI  - NMC appeals for views of mental health and learning disability registrants.
AB  - Mental health and learning disability nurses are being urged to express their
      views on how continuing fitness to practise will be assessed in the future. 

PMID- 24916217
TI  - Lifelong learning investment plan to retain workers.
AB  - More money will be invested in the training and development of the current NHS
      workforce over the next 15 years, according to the national body responsible for
      educating health workers. 

PMID- 24916218
TI  - A day of remembrance for D-Day sister.
AB  - One of the first British nurses to land in Normandy after D-Day returned to
      France with fellow veterans to mark the 70th anniversary of the operation. 

PMID- 24916219
TI  - Nurses feel 'impotent, alone and unheard', whistleblower tells NHS.
AB  - The nurse whistleblower who helped expose the Mid Staffs scandal has warned front
      line staff were still being ignored when trying to raise concerns about poor
      care, and that major problems remain in the NHS. 

PMID- 24916220
TI  - 'Staff need to boost mums' body image'.
AB  - Health visitors and midwives should not refer to high-calorie foods such as
      biscuits as 'naughty' when talking to expectant and new mothers in case they
      damage the women's body image, says a study. 

PMID- 24916222
TI  - Breast cancer pledge helps to improve services.
AB  - Specialist nurses at York Teaching Hospital NHS Foundation Trust are providing
      one-to-one support to patients with secondary breast cancer, in co-operation with
      two charities. 

PMID- 24916223
TI  - Art imitates life in a patient's tale.
AB  - The NHS is taking centre stage in a critically-acclaimed play about one family's
      experience of the health service. 

PMID- 24916224
TI  - Call for diabetes screening to be standard in every care home.
AB  - Screening for diabetes should be carried out in every older people's care home,
      researchers state. 

PMID- 24916226
TI  - RCN activists prepare to shape policy as they head to Liverpool.
AB  - Thousands of nurses will descend on Liverpool next week for the RCN's annual
      congress. 

PMID- 24916228
TI  - NMC fees increase moves closer after ministers fail to change law.
AB  - The Nursing and Midwifery Council (NMC) has been dealt a 'hugely disappointing'
      blow after the government abandoned proposals to transform healthcare regulation.

PMID- 24916229
TI  - A future nurse of the year?
AB  - Meet Pepper, the robot who could one day be programmed to provide nursing care. 

PMID- 24916236
TI  - Constipation in children.
AB  - Essential facts Up to 30 per cent of children and young people suffer from
      constipation, which can have a significant emotional impact on them and their
      families. The National Institute for Health and Care Excellence (NICE) says many
      children and young people experience social, psychological and educational
      consequences. Constipation is called idiopathic if it cannot be explained by
      anatomical or physiological abnormalities. 

PMID- 24916237
TI  - Spotlight on the RCN's professional activity.
AB  - The RCN wants to increase the scope and improve the visibility of its
      professional role, while ensuring its activity is recognised and valued by
      members. This will be discussed at the Fellows Fringe at RCN congress and
      exhibition in Liverpool on Monday June 16.

PMID- 24916238
TI  - Defence nursing: a force for good care.
AB  - Director of army nursing services David Bates has a leading role in defence
      nursing policy, training, education and research. He ensures defence nurses meet
      NMC standards while delivering care in demanding, often hostile environments. Col
      Bates believes that the NHS has much to learn from defence nursing in terms of
      leadership and valuing staff.But the future, he says, will involve increasing
      partnership between defence and civilian nurses, so he will also be looking for
      lessons from the NHS, private and third sectors.

PMID- 24916239
TI  - Code spells out the core duties of care.
AB  - The draft Code spells out the "fundamentals of basic care" nurses and midwives
      must deliver. Critics say the new document is unnecessarily detailed and insults
      nurses. But some nurse managers at organisations striving for improvements, say
      the explicit focus on core duties is timely and appropriate.

PMID- 24916248
TI  - State of mind.
AB  - The State of Mind programme was set up in 2011 to improve the mental health and
      wellbeing of rugby league players and their communities after the suicide of
      Wigan and England player Terry Newton. 

PMID- 24916252
TI  - Fund returners to practice and the staffing crisis will be solved.
AB  - I read with interest 'The NHS needs you - call goes out to nurses who left the
      profession' (Analysis May 28). 

PMID- 24916253
TI  - Taking a nursing degree is the best route into the profession for HCAs.
AB  - I welcome the Shape of Caring review that will look into the healthcare assistant
      role and paths to becoming a nurse (News May 14). 

PMID- 24916254
TI  - Technology to the rescue for language translation.
AB  - I agree with nurse lecturer Gloria Likupe that healthcare professionals need
      encouragement to respond to the UK's increasing cultural diversity by providing
      culturally competent care (Art & Science June 4). 

PMID- 24916256
TI  - It's our duty to go the extra mile for patients who are vulnerable.
AB  - Thank you for publishing Gloria Likupe's insightful article on communicating with
      older minority ethnic patients (Art & Science June 4). 

PMID- 24916257
TI  - Scare stories about Muslim nurses incite hostility towards Islam.
AB  - I am concerned by a number of articles circulating online and on social media
      sites such as Facebook that are presenting misleading information about Muslim
      nurses. 

PMID- 24916258
TI  - Self-screening for sexually transmitted infections.
AB  - There is an increasing trend towards self-collection of samples for sexually
      transmitted infection screening in lieu of genital examination and clinician
      obtained urethral and cervical swabs. This article examines the advantages and
      disadvantages of this trend, and the effect on nursing practice particularly
      within integrated sexual health (ISH) services, which provide genito-urinary
      medicine (GUM) and contraceptive services. This article might also be of interest
      to nurses working within separate GUM and contraceptive services, especially
      those that are preparing to become ISH services. 

PMID- 24916259
TI  - Experience of nursing students with dyslexia on clinical placement.
AB  - A review of the literature was conducted to explore the experience of nursing
      students with dyslexia while on clinical placement. Three main themes emerged,
      including risk to patient safety, disclosure of dyslexia and support for nursing
      students. The literature review highlights the lack of dyslexia awareness and
      understanding in the research and at the trusts at which nursing students are
      placed, and calls for further research in this area. 

PMID- 24916260
TI  - Diagnosis and management of patients with pleural effusions.
AB  - Pleural effusions occur when fluid accumulates between the visceral and parietal
      pleura in the chest cavity, preventing the lung from expanding fully during
      inspiration. The reduction in lung volume, depression of the diaphragm and
      reduced chest wall compliance cause dyspnoea, and occasionally pain or cough.
      Pleural effusion is a complex problem caused by a variety of conditions requiring
      different treatment depending on the underlying diagnosis. This article discusses
      the causes and treatment of pleural effusions, referencing guidelines produced by
      the British Thoracic Society. 

PMID- 24916261
TI  - CPD practice profile. Lung cancer.
AB  - As an agency nurse at a community hospital, I recently cared for a patient with
      cancer who had taken part in a clinical trial in which she had undergone
      chemotherapy. 

PMID- 24916262
TI  - A lasting impression.
AB  - Job applications do not stop with your CV, cover letter or application form.
      Social media such as Facebook, Twitter and LinkedIn mean employers have a wealth
      of extra information about candidates at their fingertips. 

PMID- 24916263
TI  - Masterclass in mental health.
AB  - This year's RCN congress will debate the need for practice nurses to have a
      recognised qualification. Meanwhile, a new training programme has been giving
      practice and community nurses the skills and confidence to manage patients with
      symptoms of mental illness. 

PMID- 24916265
TI  - Working in Australia.
AB  - Although my husband wanted to emigrate to Australia, it took me five years to
      warm to the idea. Another windy, wet winter in the UK finally persuaded me. 

PMID- 24916266
TI  - Student life. Exposure to research work.
AB  - University Hospitals of Leicester NHS Trust is one of the top ten trusts for
      recruiting patients to research studies. Although research nurses constitute the
      largest specialist nurse group in the trust, comprising three per cent of the
      nursing workforce, their roles and the benefits they bring are poorly understood.

PMID- 24916268
TI  - Attainment of surgical competence in otolaryngology training.
AB  - OBJECTIVES/HYPOTHESIS: Our aim was to determine the postgraduate year (PGY) of
      residency at which residents achieve competence in key otolaryngologic procedures
      as perceived by residents and program directors (PDs), determine resident or
      programmatic factors affecting PGY at which residents perceive attainment of
      competence, and evaluate the relationship between resident and PD perceptions for
      attainment of competence in these procedures. STUDY DESIGN: Cross-sectional
      survey. METHODS: We surveyed residents and PDs in US otolaryngology residencies
      in 2011 using SurveyMonkey.com and assessed subjective attainment of competence
      by residents for 32 otolaryngologic procedures. PGY at which subjective
      competence achieved per resident perception was determined using a logistic
      regression model; PD perception was determined by mean calculation. RESULTS: Two
      hundred seventy-seven residents (19.45%) and 39 PDs (37.86%) completed surveys.
      Residents achieved subjective competence later than expected by PDs for 25 of 32
      procedures, although differences were generally small. The largest disparities
      were observed for nonsurgical office-based procedures, for which <90% of
      residents reported competence by PGY-5, whereas PDs expected competence before
      PGY-3. The greatest number of disparities was present in the subspecialty area of
      facial plastic and reconstructive surgery. Male gender predicted earlier self
      reported attainment of competence in 10 of 32 procedures (P < .05). Degrees held,
      fellowship plans, and the size of the program were not significant predictors of
      PGY at which residents reported competence for most procedures. CONCLUSIONS: We
      provide baseline data on PGY at which residents and PDs feel competence is
      achieved in key otolaryngologic procedures. These results may guide milestone
      development for resident training and assessment. LEVEL OF EVIDENCE: NA.

PMID- 24916270
TI  - Epilepsies associated with focal cortical dysplasias (FCDs).
AB  - Focal cortical dysplasias (FCDs) are increasingly recognized as one of the most
      common causes of pharmaco-resistant epilepsies. FCDs were recently divided into
      various clinico-pathological subtypes due to distinct imaging,
      electrophysiological, and outcome characteristics. In this review, we will
      overview the international consensus classification of FCDs in light of more
      recently reported clinical, electrical, imaging and functional observations, and
      will also address areas of ongoing debate. In addition, we will summarize our
      current knowledge on pathobiology and epileptogenicity of FCDs as well as its
      underlying molecular and cellular mechanisms. The clinical
      (electroencephalographic, imaging, and functional) characteristics of major FCD
      subtypes and their implications on the presurgical evaluation and surgical
      management will be discussed in light of studies describing these characteristics
      and postoperative seizure outcomes in patients with medically intractable focal
      epilepsy due to histopathologically confirmed FCDs.

PMID- 24916269
TI  - TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord.
AB  - We examined the phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43)
      inclusions as well as neuronal loss in full-length spinal cords and five selected
      regions of the central nervous system from 36 patients with amyotrophic lateral
      sclerosis (ALS) and 10 age-matched normal controls. The most severe neuronal loss
      and pTDP-43 lesions were seen in lamina IX motor nuclei columns 4, 6, and 8 of
      lower cervical segments and in columns 9-11 of lumbosacral segments. Severity of
      pTDP-43 pathology and neuronal loss correlated closely with gray and white matter
      oligodendroglial involvement and was linked to onset of disease, with severe
      involvement of columns 4, 6, and 8 of upper extremity onset cases and severe
      involvement of columns of 9, 10, and 11 in cases with lower extremity onset.
      Severe TDP-43 lesions and neuronal loss were observed in stage 4 cases and
      sometimes included Onuf's nucleus. Notably, three cases displayed pTDP-43
      aggregates in the midbrain oculomotor nucleus, which we had not seen previously
      even in cases with advanced (i.e., stage 4) pathology. pTDP-43 aggregates were
      observed in neurons of Clarke's column in 30.6 % of cases but rarely in the
      intermediolateral nucleus (IML). Gray matter oligodendroglial pTDP-43 inclusions
      were present in areas devoid of neuronal pTDP-43 aggregates and neuronal loss.
      Taken together, our findings indicate that (1) the dorsolateral motor nuclei
      columns of the cervical and lumbosacral anterior horn may be the earliest foci of
      pTDP-43 pathology in the spinal cord, (2) gray matter oligodendroglial
      involvement is an early event in the ALS disease process that possibly heralds
      subsequent involvement of neurons by pTDP-43 pathology, and (3) in some very
      advanced cases, there is oculomotor nucleus involvement, which may constitute an
      additional neuropathological stage (designated here as stage 5) of pTDP-43
      pathology in ALS. 

PMID- 24916271
TI  - A comparison of Abeta amyloid pathology staging systems and correlation with
      clinical diagnosis.
AB  - Current neuropathological Alzheimer's disease (AD) criteria from the National
      Institute on Aging-Alzheimer's Association (NIA-AA) incorporate two staging
      systems for Abeta pathology, namely the Thal Abeta phase (TAP) and the Consortium
      to Establish a Registry for Alzheimer's Disease (CERAD) methods. The goal of this
      study was to compare and contrast results obtained with these two different
      staging systems for Abeta pathology since this is critical for future
      correlations of Abeta amyloid imaging data with Abeta neuropathology data based
      on immunohistochemical detection of Abeta deposits. A total of 123 cases, divided
      into 82 training and 41 validation cases, with a diagnosis of either unremarkable
      adult brain (normal) or AD and CERAD scores ranging from none to frequent were
      included. There was no clear and consistent relationship between CERAD and the
      TAP Abeta scores with the exception of scores for the highest plaque burdens
      (i.e., CERAD C3 and TAP A3) in the cases studied here. However, we developed an
      algorithm that relates CERAD scores to TAP scores with high agreement (94 % in
      training and 98 % in the validation set). In addition, TAP scores were a better
      predictor of dementia (sensitivity of 94 % specificity 87.7 %) than CERAD scores
      (sensitivity of 57 % specificity 100 %). Yet, further research is needed to
      define strategies to relate CERAD and TAP Abeta plaque scores to compare their
      utility and for determining the clinical associations of these different amyloid
      staging systems with aging and AD. 

PMID- 24916272
TI  - 'My mentor kicked a dying woman's bed...' analysing UK nursing students' 'most
      memorable' professionalism dilemmas.
AB  - AIM: To provide depth and breadth in the analysis of nursing students' written
      narratives of 'most memorable' professionalism dilemmas. BACKGROUND: While
      nursing students are taught professionalism through formal curricula, they
      commonly experience workplace-based professionalism dilemmas. Although non-UK
      studies have begun to explore students' lived experiences of dilemmas, they lack
      detail about when and where dilemmas occur, who is involved, what students do and
      why and how students feel. DESIGN: Online survey of healthcare students including
      294 nursing students from 15 UK nursing schools. METHOD: Nursing students
      provided a written narrative of their most memorable dilemma (December 2011-March
      2012) as part of a survey examining the impact of professionalism dilemmas on
      moral distress. We conducted thematic and discourse analysis of all narratives
      and narrative analysis of one exemplar. FINDINGS: The most common themes were
      patient care dilemmas by healthcare personnel or students, student abuse and
      consent dilemmas. Of the dilemmas, 49.6% occurred over 6 months previously, 76.2%
      occurred in hospitals and 51.9% of perpetrators were nurses. 79.3% of students
      reported acting in the face of their dilemma. Of the narratives, 88.4% contained
      negative emotion talk and numerous significant relationships existed between
      types of emotion talk and dilemmas. Our narrative analysis demonstrates the
      impact of dilemma experiences through emotion talk and more subtle devices like
      metaphor. CONCLUSION: Findings extend previous research with nursing and medical
      students. Nurse educators should help students construct emotionally coherent
      narratives to make sense of their experiences, actions and identities and to
      better prepare them for future professionalism dilemmas.

PMID- 24916273
TI  - Strain differences in fatigue and depression after experimental stroke.
AB  - Fatigue and depression are common symptoms after stroke. Animal models of
      poststroke fatigue (PSF) and poststroke depression (PSD) would facilitate the
      study of these symptoms. Spontaneous locomotor activity is as an objective
      measure of fatigue and learned helplessness an accepted correlate of depression.
      We used different rat strains to evaluate stroke-induced changes in behavior in
      hopes that interstrain differences would provide insights into the biological
      basis of these symptoms. Male Lewis, Wistar, and Sprague-Dawley (SD) rats
      underwent experimental stroke. Spontaneous activity was assessed continually
      after stroke (for up to 50 days). In a subset of animals, the forced swim test
      was performed prior to and 1 month after stroke to assess learned helplessness;
      blood was obtained at sacrifice for cytokine assay. Stroke induced strain-related
      differences in activity; Lewis rats increased spontaneous activity during the
      dark cycle, while Wistar and SD rats increased activity during the light cycle.
      The velocity of movement decreased during the dark cycle in Wistar and SD rats
      and during the light cycle in Lewis rats. Stroke also led to an increase in
      learned helplessness in Lewis rats. In summary, different patterns of behaviors
      emerge in different rat strains after stroke. Lewis rats displayed behavior
      consistent with depression but not fatigue, while Wistar and SD rats displayed
      behavior consistent with fatigue but not depression. These data argue that PSF
      and PSD are different biological constructs and suggest that analysis of strain
      related differences may provide insight into symptom pathophysiology.

PMID- 24916274
TI  - A practical approach to the treatment of low-risk childhood fever.
AB  - Fever is a common symptom of childhood infections that in itself does not require
      treatment. The UK's National Institute for Health and Care Excellence (NICE)
      advises home-based antipyretic treatment for low-risk feverish children only if
      the child appears distressed. The recommended antipyretics are ibuprofen or
      paracetamol (acetaminophen). They are equally recommended for the distressed,
      feverish child; therefore, healthcare professionals, parents and caregivers need
      to decide which of these agents to administer if the child is distressed. This
      narrative literature review examines recent data on ibuprofen and paracetamol in
      feverish children to determine any clinically relevant differences between these
      agents. The data suggest that these agents have similar safety profiles in this
      setting and in the absence of underlying health issues, ibuprofen seems to be
      more effective than paracetamol at reducing NICE's treatment criterion,
      'distress' (as assessed by discomfort levels, symptom relief, and general
      behavior). 

PMID- 24916275
TI  - Impact of 6% hydroxyethyl starch 130/0.42 and 4% gelatin on renal function in a
      pediatric animal model.
AB  - OBJECTIVES: Artificial colloids, frequently used to prevent hemorrhagic shock in
      children, may induce serious renal side effects in critically ill adult patients.
      The impact of perioperative colloid infusion on the renal function in adults and
      children remains unclear. AIM: To determine the impact of single doses of
      artificial colloids on renal function tests, we conducted an experimental animal
      study. We hypothesized that neither the infusion of moderate doses of 6%
      hydroxyethyl starch (HES) nor of 4% gelatin (GEL) would have a serious impact on
      the renal function of healthy piglets. METHODS: Fifteen sedated piglets were
      randomly assigned to receive an infusion of either 20 ml.kg(-1) HES or GEL or a
      balanced electrolyte solution (BS, control group) over 30 min. Before and 7 days
      after infusion, serum and urine renal function tests were recorded and renal
      biopsies were taken. RESULTS: Serum and urine renal function tests (e.g.,
      creatinine, urea, cystatin C, and neutrophil gelatinase-associated lipocalin)
      were within normal ranges, and a microscopic examination of the renal tissue in
      all groups revealed no major alterations such as tubular necrosis, interstitial
      bleeding, interstitial inflammation, or vacuoles. CONCLUSIONS: In this pediatric
      animal model, the infusion of moderate doses of artificial colloids was not found
      to have any relevant impact on renal function. Further clinical investigations
      are necessary to provide a conclusive assessment of the risk for renal impairment
      after HES and GEL administration during major pediatric surgery.

PMID- 24916276
TI  - Sumoylation of hypoxia inducible factor-1alpha and its significance in cancer.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a key heterodimeric transcription factor
      for the cellular adaptive response to hypoxia, a common feature of the
      microenvironment in solid tumors. The transcriptional activity, protein
      stabilization, protein-protein interactions and cellular localization of HIF
      1alpha, an oxygen-sensitive subunit of HIF-1, are mainly modulated by various
      post-translational modifications. Recently, we reported that polycomb chromobox 4
      (Cbx4) governs the transcriptional activity of HIF-1alpha by enhancing its
      sumoylation at K391 and K477, through which Cbx4 potentiates angiogenesis of
      hepatocellular carcinoma. This review summarizes the current knowledge of HIF
      1alpha sumoylation and its roles in the pathogenesis of cancer. 

PMID- 24916277
TI  - Tooth enamel hypoplasia in PHACE syndrome.
AB  - Individuals with PHACE syndrome (posterior fossa malformations, hemangiomas,
      arterial anomalies, cardiac defects, eye abnormalities, sternal cleft, and
      supraumbilical raphe syndrome) have reported dental abnormalities to their
      healthcare providers and in online forums, but dental involvement has not been
      comprehensively studied. A study was conducted at the third PHACE Family
      Conference, held in Milwaukee, Wisconsin, in July 2012. A pediatric dentist
      examined subjects at enrollment. Eighteen subjects were enrolled. The median age
      was 4.2 years (range 9 mos-9 yrs; 14 girls, 4 boys). Eleven of 18 patients had
      intraoral hemangiomas and five of these (50%) had hypomature enamel hypoplasia.
      None of the seven patients without intraoral hemangiomas had enamel hypoplasia.
      No other dental abnormalities were seen. Enamel hypoplasia may be a feature of
      PHACE syndrome when an intraoral hemangioma is present. Enamel hypoplasia
      increases the risk of caries, and clinicians should refer children with PHACE
      syndrome to a pediatric dentist by 1 year of age. 

PMID- 24916278
TI  - Can chemotherapy alone eliminate the transmission of soil transmitted helminths?
AB  - BACKGROUND: Amongst the world's poorest populations, availability of anthelmintic
      treatments for the control of soil transmitted helminths (STH) by mass or
      targeted chemotherapy has increased dramatically in recent years. However, the
      design of community based treatment programmes to achieve the greatest impact on
      transmission is still open to debate. Questions include: who should be treated,
      how often should they be treated, how long should treatment be continued for?
      METHODS: Simulation and analysis of a dynamic transmission model and novel data
      analyses suggest refinements of the World Health Organization guidelines for the
      community based treatment of STH. RESULTS: This analysis shows that treatment
      levels and frequency must be much higher, and the breadth of coverage across age
      classes broader than is typically the current practice, if transmission is to be
      interrupted by mass chemotherapy alone. CONCLUSIONS: When planning interventions
      to reduce transmission, rather than purely to reduce morbidity, current school
      based interventions are unlikely to be enough to achieve the desired results.

PMID- 24916279
TI  - SaOS2 Osteosarcoma cells as an in vitro model for studying the transition of
      human osteoblasts to osteocytes.
AB  - The central importance of osteocytes in regulating bone homeostasis is becoming
      increasingly apparent. However, the study of these cells has been restricted by
      the relative paucity of cell line models, especially those of human origin.
      Therefore, we investigated the extent to which SaOS2 human osteosarcoma cells can
      differentiate into osteocyte-like cells. During culture under the appropriate
      mineralising conditions, SaOS2 cells reproducibly synthesised a bone-like
      mineralised matrix and temporally expressed the mature osteocyte marker genes
      SOST, DMP1, PHEX and MEPE and down-regulated expression of RUNX2 and COL1A1.
      SaOS2 cells cultured in 3D collagen gels acquired a dendritic morphology,
      characteristic of osteocytes, with multiple interconnecting cell processes. These
      findings suggest that SaOS2 cells have the capacity to differentiate into mature
      osteocyte-like cells under mineralising conditions. PTH treatment of SaOS2 cells
      resulted in strong down-regulation of SOST mRNA expression at all time points
      tested. Interestingly, PTH treatment resulted in the up-regulation of RANKL mRNA
      expression only at earlier stages of differentiation. These findings suggest that
      the response to PTH is dependent on the differentiation stage of the
      osteoblast/osteocyte. Together, our results demonstrate that SaOS2 cells can be
      used as a human model to investigate responses to osteotropic stimuli throughout
      differentiation to a mature osteocyte-like stage. 

PMID- 24916281
TI  - Gape-limited predators as agents of selection on the defensive morphology of an
      invasive invertebrate.
AB  - Invasive species have widespread and pronounced effects on ecosystems and
      adaptive evolution of invaders is often considered responsible for their success.
      Despite the potential importance of adaptation to invasion, we still have limited
      knowledge of the agents of natural selection on invasive species. Bythotrephes
      longimanus, a cladoceran zooplankton, invaded multiple Canadian Shield lakes over
      the past several decades. Bythotrephes have a conspicuous caudal process (tail
      spine) that provides a morphological defense against fish predation. We measured
      viability selection on the longest component of the Bythotrephes spine, the
      distal spine segment, through a comparison of the lengths of first and second
      instar Bythotrephes collected from lakes differing in the dominance of gape
      limited predation (GLP) and nongape-limited predation (NGLP) by fish. We found
      that natural selection varied by predator gape-limitation, with strong selection
      (selection intensity: 0.20-0.79) for increased distal spine length in lakes
      dominated by GLP, and no significant selection in lakes dominated by NGLP.
      Further, distal spine length was 17% longer in lakes dominated by GLP, suggesting
      the possibility of local adaptation. As all study lakes were invaded less than 20
      years prior to our collections, our results suggest rapid divergence in defensive
      morphology in response to selection from fish predators.

PMID- 24916280
TI  - Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic
      targets: IUPHAR review 10.
AB  - GPCRs can interact with each other to form homomers or heteromers. Homomers
      involve interactions with the same receptor type while heteromers involve
      interactions between two different GPCRs. These receptor-receptor interactions
      modulate not only the binding but also the signalling and trafficking properties
      of individual receptors. Opioid receptor heteromerization has been extensively
      investigated with the objective of identifying novel therapeutic targets that are
      as potent as morphine but without the side effects associated with chronic
      morphine use. In this context, studies have described heteromerization between
      the different types of opioid receptors and between opioid receptors and a wide
      range of GPCRs including adrenoceptors, cannabinoid, 5-HT, metabotropic glutamate
      and sensory neuron-specific receptors. Recent advances in the field involving the
      generation of heteromer-specific reagents (antibodies or ligands) or of membrane
      permeable peptides that disrupt the heteromer interaction are helping to
      elucidate the physiological role of opioid receptor heteromers and the
      contribution of the partner receptor to the side effects associated with opioid
      use. For example, studies using membrane-permeable peptides targeting the
      heteromer interface have implicated MU and delta receptor heteromers in the
      development of tolerance to morphine, and heteromers of MU and gastrin-releasing
      peptide receptors in morphine-induced itch. In addition, a number of ligands that
      selectively target opioid receptor heteromers exhibit potent antinociception with
      a decrease in the side effects commonly associated with morphine use. In this
      review, we summarize the latest findings regarding the biological and functional
      characteristics of opioid receptor heteromers both in vitro and in vivo. 

PMID- 24916282
TI  - Effects of microplasma irradiation on human gingival fibroblasts.
AB  - The purpose of this research was to clarify the effects of microplasma
      irradiation on human gingival fibroblasts (HGF). Microplasma irradiation exposure
      for all HGF samples was limited to 30 s at an irradiation distance of 10 mm with
      a gas flow of 10 L/min. Three experimental groups were used: a 0 V control group
      (Control); a 650 V (low) microplasma irradiation group (LV); and a 975 V (high)
      irradiation group (HV). The following cellular characteristics were evaluated in
      order to analyze the effects of microplasma treatment; morphology, cell count,
      DNA content, metabolic activity, cell migration, fibroblast growth factor beta
      (FGF-2) production, type I collagen secretion, and cytotoxic analysis. Cell
      count, DNA content and FGF-2 production have all been linked to wound healing
      and, interestingly, both the LV and HV groups showed significant (P < 0.05)
      increases in these categories at 72 h after irradiation when compared to the
      control group. Cytotoxic effects were measured by determining the levels of
      lactate dehydrogenase, cell death, and DNA damage in HGF cells. In these
      analyses, the HV and LV groups were not statistically different when compared
      with the control group at 72 h post-irradiation. These findings suggest that
      microplasma irradiation activated HGF with no clear cell-damaging effects.

PMID- 24916283
TI  - A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of
      small molecules in extracellular matrix gels used in 3D cultures is dominated by
      viscous effects.
AB  - The design of 3D culture studies remains challenging due to the limited
      understanding of extracellular matrix (ECM)-dependent hindered diffusion and the
      lack of simple diffusivity assays. To address these limitations, we set up a cost
      effective diffusivity assay based on a Transwell plate and the spectrophotometer
      of a Microplate Reader, which are readily accessible to cell biology groups. The
      spectrophotometer-based assay was used to assess the apparent diffusivity D of
      FITC-dextrans with molecular weight (4-70kDa) spanning the physiological range of
      signaling factors in a panel of acellular ECM gels including Matrigel, fibrin and
      type I collagen. Despite their technical differences, D data exhibited ~15%
      relative difference with respect to FRAP measurements. Our results revealed that
      diffusion hindrance of small particles is controlled by the enhanced viscosity of
      the ECM gel in conformance with the Stokes-Einstein equation rather than by
      geometrical factors. Moreover, we provided a strong rationale that the enhanced
      ECM viscosity is largely contributed to by unassembled ECM macromolecules. We
      also reported that gels with the lowest D exhibited diffusion hindrance closest
      to the large physiologic hindrance of brain tissue, which has a typical pore size
      much smaller than ECM gels. Conversely, sparse gels (<=1mg/ml), which are
      extensively used in 3D cultures, failed to reproduce the hindered diffusion of
      tissues, thereby supporting that dense (but not sparse) ECM gels are suitable
      tissue surrogates in terms of macromolecular transport. Finally, the consequences
      of reduced diffusivity in terms of optimizing the design of 3D culture
      experiments were addressed in detail. 

PMID- 24916284
TI  - Assessing the effect of surface modification of polyamide RO membrane by l-DOPA
      on the short range physiochemical interactions with biopolymer fouling on the
      membrane.
AB  - Theoretical predictions of interaction energies for membrane-biopolymer foulant
      pairs were used to compare the fouling tendencies of a virgin commercial
      polyamide reverse osmosis (RO) membrane with a amino acid 3-(3,4-dihydroxyphenyl)
      l-alanine (l-DOPA) coated RO membrane. Lifshitz-van der Waals (LW) and Lewis acid
      base (AB) surface tension components of the membranes were determined based on
      contact angle results using the van Oss approach. From these values, the LW and
      AB components of the free energy of adhesion between membrane and foulants were
      calculated. Electrostatic (EL) double layer interaction energies between the
      membrane and foulants were also estimated using the measured surface charge data
      of the membranes and fouling agents. Bovine serum albumin (BSA) and alginic acid
      sodium salt (alginate) were used as model biopolymers causing membrane fouling.
      Based on the calculated adhesion free energies, acid-base interactions were found
      to have the strongest impact on the adhesion of both BSA and alginate to the
      either membranes surfaces. It was found that l-DOPA modification has
      significantly lowered acid-base interaction affinity toward the adhesion of both
      foulants studied. On the basis of calculated free energies of adhesion, lower
      fouling tendency of the l-DOPA modified membrane was expected. The accelerated
      fouling tests indicated a lower flux decline rate for the modified membrane and
      confirmed the results obtained from theory. 

PMID- 24916285
TI  - Terminated.

PMID- 24916286
TI  - Lymph node status as a prognostic indicator after preoperative neoadjuvant
      chemoradiotherapy of rectal cancer.
AB  - AIM: The primary aim of this study was to examine lymph node status after
      neoadjuvant chemoradiotherapy (CRT) using a novel scoring system describing the
      pathological lymph node regression grade. The proposed scoring system was based
      on the percentage of fibrosis and the presence of residual tumour amount. The
      secondary aim of the study was to assess the oncological impact of this scoring
      system. METHOD: The project was a retrospective cohort study over a 10-year
      period. Two hundred and two patients with rectal cancer who had received CRT
      followed by curative surgery were included. A histopathologist prospectively
      scored each specimen and the impact of the scoring system on survival and
      recurrence was analysed. RESULTS: One hundred and ninety patients completed long
      course preoperative CRT and formed the basis of the study. Overall, 40
      recurrences (local and distant) were observed over a median follow-up of 36
      months. The lymph node regression score was a significant predictor of tumour
      recurrence (hazard ratio 1.273, 95% CI 1.048-1.548; P = 0.015). The overall
      mortality rate was 21%, and a lower lymph node regression score was correlated
      with an improved survival curve (P = 0.01). CONCLUSION: The results demonstrate
      that lymph node response to neoadjuvant CRT based on a nodal regression scoring
      system is related to recurrence.

PMID- 24916287
TI  - Long-term depression as a model of cerebellar plasticity.
AB  - Long-term depression (LTD) here concerned is persistent attenuation of
      transmission efficiency from a bundle of parallel fibers to a Purkinje cell.
      Uniquely, LTD is induced by conjunctive activation of the parallel fibers and the
      climbing fiber that innervates that Purkinje cell. Cellular and molecular
      processes underlying LTD occur postsynaptically. In the 1960s, LTD was conceived
      as a theoretical possibility and in the 1980s, substantiated experimentally.
      Through further investigations using various pharmacological or genetic
      manipulations of LTD, a concept was formed that LTD plays a major role in
      learning capability of the cerebellum (referred to as "Marr-Albus-Ito
      hypothesis"). In this chapter, following a historical overview, recent intensive
      investigations of LTD are reviewed. Complex signal transduction and receptor
      recycling processes underlying LTD are analyzed, and roles of LTD in reflexes and
      voluntary movements are defined. The significance of LTD is considered from
      viewpoints of neural network modeling. Finally, the controversy arising from the
      recent finding in a few studies that whereas LTD is blocked pharmacologically or
      genetically, motor learning in awake behaving animals remains seemingly unchanged
      is examined. We conjecture how this mismatch arises, either from a methodological
      problem or from a network nature, and how it might be resolved. 

PMID- 24916288
TI  - The organization of plasticity in the cerebellar cortex: from synapses to
      control.
AB  - The cerebellum is thought to play a critical role in procedural learning, but the
      relationship between this function and the underlying cellular and synaptic
      mechanisms remains largely speculative. At present, at least nine forms of long
      term synaptic and nonsynaptic plasticity (some of which are bidirectional) have
      been reported in the cerebellar cortex and deep cerebellar nuclei. These include
      long-term potentiation (LTP) and long-term depression at the mossy fiber-granule
      cell synapse, at the synapses formed by parallel fibers, climbing fibers, and
      molecular layer interneurons on Purkinje cells, and at the synapses formed by
      mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP
      of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar
      nuclear cells. It is suggested that the complex properties of cerebellar learning
      would emerge from the distribution of plasticity in the network and from its
      dynamic remodeling during the different phases of learning. Intrinsic and
      extrinsic factors may hold the key to explain how the different forms of
      plasticity cooperate to select specific transmission channels and to regulate the
      signal-to-noise ratio through the cerebellar cortex. These factors include
      regulation of neuronal excitation by local inhibitory networks, engagement of
      specific molecular mechanisms by spike bursts and theta-frequency oscillations,
      and gating by external neuromodulators. Therefore, a new and more complex view of
      cerebellar plasticity is emerging with respect to that predicted by the original
      "Motor Learning Theory," opening issues that will require experimental and
      computational testing. 

PMID- 24916289
TI  - Questioning the cerebellar doctrine.
AB  - The basic principles of cerebellar function were originally described by
      Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can
      be considered to be the classic cerebellar doctrine. In their concepts, the main
      cerebellar function is to control motor behavior, Purkinje cells are the only
      cortical neuron receiving and integrating inputs from climbing fiber and mossy
      parallel fiber pathways, and plastic modification at the parallel fiber synapses
      onto Purkinje cells constitutes the substrate of motor learning. Yet, because of
      recent technical advances and new angles of investigation, all pillars of the
      cerebellar doctrine now face regular re-examination. In this review, after
      summarizing the classic concepts and recent disputes, we attempt to synthesize an
      integrated view and propose a revisited version of the cerebellar doctrine. 

PMID- 24916290
TI  - Distribution of neural plasticity in cerebellum-dependent motor learning.
AB  - The cerebellum is essential for some forms of motor learning. Two examples that
      provide useful experimental models are modification of the vestibulo-ocular
      reflex and classical conditioning of the nictitating membrane response (NMR) in
      the rabbit. There has been considerable analysis of these behavioral models and
      of conditioning of the eyelid blink reflex, which is similar in several respects
      to NMR conditioning but with some key differences in its control circuitry. The
      evidence is consistent with the suggestion that storage of these motor memories
      is to be found within the cerebellum and its associated brainstem circuitry. The
      cerebellum presents many advantages as a model system to characterize the
      cellular and molecular mechanisms underpinning behavioral learning. And yet,
      localizing the essential synaptic changes has proven to be difficult. A major
      problem has been to establish to what extent these neural changes are distributed
      through the cerebellar cortex, cerebellar nuclei, and associated brainstem
      nuclei. Inspired by recent theoretical work, here we review evidence that the
      distribution of plasticity across cortical and cerebellar nuclear (or brainstem
      vestibular system) levels for different learning tasks may be different and
      distinct. Our primary focus is on classical conditioning of the NMR and eyelid
      blink, and we offer comparisons with mechanisms for modifications of the
      vestibulo-ocular reflex. We describe a view of cerebellar learning that satisfies
      theoretical and empirical analysis. 

PMID- 24916291
TI  - Feedback control of learning by the cerebello-olivary pathway.
AB  - The ability to anticipate future events and to modify erroneous anticipatory
      actions is crucial for the survival of any organism. Both theoretical and
      empirical lines of evidence implicate the cerebellum in this ability. It is often
      suggested that the cerebellum acquires "expectations" or "internal models."
      However, except in a metaphorical sense, the cerebellum, which consists of a set
      of interconnected nerve cells, cannot contain "internal models" or "have
      expectations." In this chapter, we try to untangle these metaphors by translating
      them back into neurophysiological cause and effect relationships. We approach
      this task from within the paradigm of classical conditioning, in which a subject,
      through repeated presentations of a conditional stimulus, followed by an
      unconditional stimulus, acquires a conditioned response. Importantly, the
      conditioned response is timed so that it anticipates the unconditioned response.
      Available neurophysiological evidence suggests that Purkinje cells, in the
      cerebellar cortex, generate the conditioned response. In addition, Purkinje cells
      provide negative feedback to the inferior olive, which is a relay for the
      unconditional stimulus, via the nucleo-olivary pathway. Purkinje cells can
      therefore regulate the intensity of the signal derived from the unconditional
      stimulus, which, in turn, decides subsequent plasticity. Hence, as learning
      progresses, the olivary signal will become weaker and weaker due to increasing
      negative feedback from Purkinje cells. Thus, in an important sense, learning
      induced changes in Purkinje cell activity constitute an "expectation" or
      "anticipation" of a future event (the unconditional stimulus), and, consistent
      with theoretical models, future learning depends on the accuracy of this
      expectation. 

PMID- 24916292
TI  - Cerebellum-dependent motor learning: lessons from adaptation of eye movements in
      primates.
AB  - In order to ameliorate the consequences of ego motion for vision, human and
      nonhuman observers generate reflexive, compensatory eye movements based on visual
      as well as vestibular information, helping to stabilize the images of visual
      scenes on the retina despite ego motion. And in order to fully exploit the
      advantages of foveal vision, they make saccades to shift the image of an object
      onto the fovea and smooth pursuit eye movements to stabilize it there despite
      continuing object movement relative to the observer. With the exception of slow
      visually driven eye movements, which can be understood as manifestations of
      relatively straightforward feedback systems, most eye movements require a direct
      conversion of sensory input into appropriate motor responses in the absence of
      immediate sensory feedback. Hence, in order to generate appropriate oculomotor
      responses, the parameters linking input and output must be chosen suitably.
      Moreover, as the parameters may change from one manifestation of a movement to
      the next, for instance because of oculomotor fatigue, the choices should also be
      quickly modifiable. This chapter will present evidence showing that this fast
      parametric optimization, understood as a functionally distinct example of motor
      learning, is an accomplishment of specific parts of the cerebellum devoted to the
      control of eye movements. It will also discuss recent electrophysiological
      results suggesting how this specific form of motor learning may emerge from
      information processing in cerebellar circuits. 

PMID- 24916293
TI  - Decorrelation learning in the cerebellum: computational analysis and experimental
      questions.
AB  - Many cerebellar models use a form of synaptic plasticity that implements
      decorrelation learning. Parallel fibers carrying signals positively correlated
      with climbing-fiber input have their synapses weakened (long-term depression),
      whereas those carrying signals negatively correlated with climbing input have
      their synapses strengthened (long-term potentiation). Learning therefore ceases
      when all parallel-fiber signals have been decorrelated from climbing-fiber input.
      This is a computationally powerful rule for supervised learning and can be cast
      in a spike-timing dependent plasticity form for comparison with experimental
      evidence. Decorrelation learning is particularly well suited to sensory
      prediction, for example, in the reafference problem where external sensory
      signals are interfered with by reafferent signals from the organism's own
      movements, and the required circuit appears similar to the one found to mediate
      classical eye blink conditioning. However, for certain stimuli, avoidance is a
      much better option than simple prediction, and decorrelation learning can also be
      used to acquire appropriate avoidance movements. One example of a stimulus to be
      avoided is retinal slip that degrades visual processing, and decorrelation
      learning appears to play a role in the vestibulo-ocular reflex that stabilizes
      gaze in the face of unpredicted head movements. Decorrelation learning is thus
      suitable for both sensory prediction and motor control. It may also be well
      suited for generic spatial and temporal coordination, because of its ability to
      remove the unwanted side effects of movement. Finally, because it can be used
      with any kind of time-varying signal, the cerebellum could play a role in
      cognitive processing. 

PMID- 24916294
TI  - Modeling the evolution of the cerebellum: from macroevolution to function.
AB  - The purpose of this contribution is to explore how macroevolutionary studies of
      the cerebellum can contribute to theories on cerebellar function and
      connectivity. New approaches in modeling the evolution of biological traits have
      provided new insights in the evolutionary pathways that underlie cerebellar
      evolution. These approaches reveal patterns of coordinated size changes among
      brain structures across evolutionary time, demonstrate how particular
      lineages/species stand out, and what the rate and timing of neuroanatomical
      changes were in evolutionary history. Using these approaches, recent studies
      demonstrated that changes in the relative size of the posterior cerebellar cortex
      and associated cortical areas indicate taxonomic differences in great apes and
      humans. Considering comparative differences in behavioral capacity,
      macroevolutionary results are discussed in the context of theories on cerebellar
      function and learning. 

PMID- 24916296
TI  - Automatic and controlled processing in the corticocerebellar system.
AB  - During learning, performance changes often involve a transition from controlled
      processing in which performance is flexible and responsive to ongoing error
      feedback, but effortful and slow, to a state in which processing becomes swift
      and automatic. In this state, performance is unencumbered by the requirement to
      process feedback, but its insensitivity to feedback reduces its flexibility. Many
      properties of automatic processing are similar to those that one would expect of
      forward models, and many have suggested that these may be instantiated in
      cerebellar circuitry. Since hierarchically organized frontal lobe areas can both
      send and receive commands, I discuss the possibility that they can act both as
      controllers and controlled objects and that their behaviors can be independently
      modeled by forward models in cerebellar circuits. Since areas of the prefrontal
      cortex contribute to this hierarchically organized system and send outputs to the
      cerebellar cortex, I suggest that the cerebellum is likely to contribute to the
      automation of cognitive skills, and to the formation of habitual behavior which
      is resistant to error feedback. An important prerequisite to these ideas is that
      cerebellar circuitry should have access to higher order error feedback that
      signals the success or failure of cognitive processing. I have discussed the
      pathways through which such feedback could arrive via the inferior olive and the
      dopamine system. Cerebellar outputs inhibit both the inferior olive and the
      dopamine system. It is possible that learned representations in the cerebellum
      use this as a mechanism to suppress the processing of feedback in other parts of
      the nervous system. Thus, cerebellar processes that control automatic performance
      may be completed without triggering the engagement of controlled processes by
      prefrontal mechanisms. 

PMID- 24916297
TI  - Preface. Cerebellar learning.

PMID- 24916295
TI  - Cerebellar and prefrontal cortex contributions to adaptation, strategies, and
      reinforcement learning.
AB  - Traditionally, motor learning has been studied as an implicit learning process,
      one in which movement errors are used to improve performance in a continuous,
      gradual manner. The cerebellum figures prominently in this literature given well
      established ideas about the role of this system in error-based learning and the
      production of automatized skills. Recent developments have brought into focus the
      relevance of multiple learning mechanisms for sensorimotor learning. These
      include processes involving repetition, reinforcement learning, and strategy
      utilization. We examine these developments, considering their implications for
      understanding cerebellar function and how this structure interacts with other
      neural systems to support motor learning. Converging lines of evidence from
      behavioral, computational, and neuropsychological studies suggest a fundamental
      distinction between processes that use error information to improve action
      execution or action selection. While the cerebellum is clearly linked to the
      former, its role in the latter remains an open question. 

PMID- 24916298
TI  - On the latent structure of problem gambling: a taxometric analysis.
AB  - AIMS: To test whether problem gambling is a categorical or dimensional disorder
      on the basis of two problem gambling assessments. This distinction discriminates
      between two different conceptualizations of problem gambling: one that problem
      gambling is defined by its addictive properties, the other that it is a continuum
      of harm. METHOD: Using The British Gambling Prevalence Survey 2010, a nationally
      representative sample of the United Kingdom conducted by the National Centre for
      Social Research, five different taxometric analyses were carried out on cases
      from two problem gambling screens: the Problem Gambling Severity Index (PGSI) and
      a measure derived from the DSM-IV Pathological Gambling criteria. Two further
      analyses were conducted on the total scores for these measures. RESULTS: There
      was strong evidence that both scales were measuring a categorical construct. Fit
      indices consistently supported a categorical interpretation [comparison curve fit
      index (CCFI) > 0.6]. The PGSI analysis indicated the presence of a taxon (CCFIs =
      0.633, 0.756). The analysis conducted on the adapted DSM-IV criteria indicated
      stronger quantitative support for a taxon (CCFIs = 0.717, 0.811 and 0.756) but
      items probing a loss of control were inconsistent. The taxometric analyses of
      both scales support a categorical interpretation (CCFIs = 0.628, 0.567), but
      extreme caution should be used due to high nuisance covariance. CONCLUSIONS: Two
      problem gambling screens (the Problem Gambling Severity Index and a measure
      derived from the DSM-IV Pathological Gambling criteria) appear to measure a
      categorical construct that taps into a categorical, loss of control model of
      problem gambling. There is some evidence that the two screens measure different
      aspects of an addiction construct.

PMID- 24916299
TI  - Consumer behaviour towards vegetables: a study on domestic processing of broccoli
      and carrots by Dutch households.
AB  - BACKGROUND: Preferences for sensory properties (e.g. taste and texture) are
      assumed to control cooking behaviour with respect to vegetables. Conditions such
      as the cooking method, amount of water used and the time-temperature profile
      determine the nutritional quality (e.g. vitamins and phytochemicals) of cooked
      vegetables. Information on domestic processing and any underlying motives can be
      used to inform consumers about cooking vegetables that are equally liked and are
      nutrient-rich. METHODS: Two online self-reporting questionnaires were used to
      identify domestic processing conditions of broccoli and carrots by Dutch
      households. Questions on various aspects of domestic processing and consumer
      motives were included. Descriptive data analysis and hierarchical cluster
      analysis were performed for both vegetables, separately, to group consumers with
      similar motives and behaviour towards vegetables. RESULTS: Approximately 70% of
      consumers boiled vegetables, 8-9% steamed vegetables, 10-15% stir fried raw
      vegetables and 8-10% stir fried boiled vegetables. Mainly texture was used as a
      way to decide the 'doneness' of the vegetables. For both vegetables, three
      clusters of consumers were identified: texture-orientated, health-orientated, or
      taste-orientated. The texture-orientated consumers are identified as the most
      prevalent (56-59%) group in the present study. Statistically significant
      associations are found between domestic processing conditions and clusters,
      whereas no such association are found between demographic details and clusters.
      CONCLUSIONS: A wide variation in domestic processing of broccoli and carrots is
      found in the present study. Mainly sensory properties (i.e. texture and taste)
      determined the domestic processing conditions. The findings of the present study
      can be used to optimise cooking to yield vegetables that meet consumer's specific
      sensory preference and are higher in nutrients, and as well as to communicate
      with target consumer groups.

PMID- 24916300
TI  - Exploring the function of genetic variants in the non-coding genomic regions:
      approaches for identifying human regulatory variants affecting gene expression.
AB  - Understanding the genetic basis of human traits/diseases and the underlying
      mechanisms of how these traits/diseases are affected by genetic variations is
      critical for public health. Current genome-wide functional genomics data
      uncovered a large number of functional elements in the noncoding regions of human
      genome, providing new opportunities to study regulatory variants (RVs). RVs play
      important roles in transcription factor bindings, chromatin states and epigenetic
      modifications. Here, we systematically review an array of methods currently used
      to map RVs as well as the computational approaches in annotating and interpreting
      their regulatory effects, with emphasis on regulatory single-nucleotide
      polymorphism. We also briefly introduce experimental methods to validate these
      functional RVs. 

PMID- 24916301
TI  - Restoration of the genus Parasaccocoelium Zhukov, 1971 (Digenea: Haploporidae)
      and a description of two new species from mugilid fish in the Far East of Russia.
AB  - New data relating to the fauna of Haploporidae (Digenea) in mugilid fish from
      Primorsky Region of the south of the Russian Far East are presented. In the most
      recent revision of the family Haploporidae Nicoll, 1914, Parasaccocoelium Zhukov,
      1971 was synonymized with Pseudohapladena Yamaguti, 1952 (Overstreet & Curran,
      2005). Here, we restore the genus Parasaccocoelium. The species described by
      Zhukov can be distinguished from the species Pseudohapladena sensu Yamaguti, 1952
      using a combination of the following features: (1) diffuse or absent eye-spot
      pigment; (2) subterminal or terminal oral sucker; (3) present or absent genital
      atrium; and (4) vitellarium with two large and compact vitelline masses, or
      vitelline follicles tubular and divided into two groups. For the species of
      Pseudohapladena, i.e. P. scatophagi, Yamaguti noted that the vitelline follicles
      occupy almost the entire post-testicular region, but in the present specimens,
      the vitelline follicles do not occupy the post-testicular region. Based on the
      diagnosis of Pseudohapladena by Overstreet & Curran (2005), the genus
      Parasaccocoelium differs in the following features: (1) a single testis that is
      longitudinal, longitudinally oval, spherical, transversally oval, irregular,
      bilobed or V-shaped, or a testis that is subspherical to irregular to elongate;
      (2) the vitellarium in the lateral fields formed from large compact follicles
      that have an irregular form and extend between the anterior margin of the ventral
      sucker or pharynx and posterior margin of the testis, and the vitelline follicles
      do not occupy post-testicular regions; or the vitellarium consists of elongate
      groups of follicles that usually extend at least one-half of a body length and
      extend to the posterior end of the body in some and to the posterior margin of
      the testis in others; (3) the eggs are operculate, unembryonated and developed
      when laid, or the eggs in some cases are only operculate; and (4) a developed
      miracidium with or without an eye spot. New data have been added to the
      description of Parasaccocoelium mugili Zhukov, 1971 based on new material, and
      two new species of this genus, Pa. haematocheilum n. sp. from Liza haematocheila
      and Pa. polyovum n. sp. from L. haematocheila and Mugil cephalus, are described
      using morphological and molecular approaches. We support the taxonomic status of
      the genus Parasaccocoelium and its inclusion within the sub-family
      Waretrematinae, and we consider Pseudohapladena lizae Liu et Yang, 2002 to be a
      junior synonym of Parasaccocoelium mugili Zhukov, 1971. 

PMID- 24916302
TI  - Caloric restriction and cancer: molecular mechanisms and clinical implications.
AB  - Caloric restriction (CR) is currently the most robust environmental intervention
      known to increase healthy life and prolong lifespan in several models, from yeast
      to mice. Although the protective effect of CR on the incidence of cancer is well
      established, its impact on tumor cell responses to chemotherapeutic treatment is
      currently being investigated. Interestingly, the molecular mechanisms required to
      extend lifespan upon reduced food intake are being evaluated, and these
      mechanisms may offer new opportunities for therapeutic intervention. In addition,
      new findings suggest a beneficial effect of CR in enhancing the efficiency of
      tumor cell killing by chemotherapeutic drugs and inducing an anticancer immune
      response. 

PMID- 24916303
TI  - Prognostic prediction and identification of candidates for salvage liver
      transplantation among patients with early hepatocellular carcinoma.

PMID- 24916304
TI  - Demonstration of the heterolytic O-O bond cleavage of putative nonheme iron(II)
      OOH(R) complexes for Fenton and enzymatic reactions.
AB  - One-electron reduction of mononuclear nonheme iron(III) hydroperoxo (Fe(III)-OOH)
      and iron(III) alkylperoxo (Fe(III)-OOR) complexes by ferrocene (Fc) derivatives
      resulted in the formation of the corresponding iron(IV) oxo complexes. The
      conversion rates were dependent on the concentration and oxidation potentials of
      the electron donors, thus indicating that the reduction of the iron(III)
      (hydro/alkyl)peroxo complexes to their one-electron reduced iron(II)
      (hydro/alkyl)peroxo species is the rate-determining step, followed by the
      heterolytic O-O bond cleavage of the putative iron(II) (hydro/alkyl)peroxo
      species to give the iron(IV) oxo complexes. Product analysis supported the
      heterolytic O-O bond-cleavage mechanism. The present results provide the first
      example showing the one-electron reduction of iron(III) (hydro/alkyl)peroxo
      complexes and the heterolytic O-O bond cleavage of iron(II) (hydro/alkyl)peroxo
      species to form iron(IV) oxo intermediates which occur in nonheme iron enzymatic
      and Fenton reactions.

PMID- 24916306
TI  - Methodological analysis of finite helical axis behavior in cervical kinematics.
AB  - Although a far more stable approach compared to the six degrees of freedom
      analysis, the finite helical axis (FHA) struggles with interpretational
      difficulties among health professionals. The analysis of the 3D-motion axis has
      been used in clinical studies, but mostly limited to qualitative analysis. The
      aim of this study is to introduce a novel approach for the quantification of the
      FHA behavior and to investigate the effect of noise and angle intervals on the
      estimation of FHA parameters. A simulation of body movement has been performed
      introducing Gaussian noise on position and orientation of a virtual sensor
      showing linear relation between the simulated noise and the error in the
      corresponding parameter. FHA axis behavior was determined by calculating the
      intersection points of the FHA with a number of planes perpendicular to the FHA
      using the Convex Hull (CH) technique. The angle between the FHA and each of the
      IHA was also computed and its distribution was also analyzed. Input noise has an
      inversely proportional relationship with the angle steps of FHA estimation. The
      proposed FHA quantification approach can be useful to provide new approaches to
      researchers and to improve insight for the clinician in order to better
      understand joint kinematics. 

PMID- 24916305
TI  - Development of the resolution theory for electrophoretic exclusion.
AB  - Electrophoretic exclusion, a technique that differentiates species in bulk
      solution near a channel entrance, has been demonstrated on benchtop and
      microdevice designs. In these systems, separation occurs when the electrophoretic
      velocity of one species is greater than the opposing hydrodynamic flow, while the
      velocity of the other species is less than that flow. Although exclusion has been
      demonstrated in multiple systems for a range of analytes, a theoretical
      assessment of resolution has not been addressed. To compare the results of these
      calculations to traditional techniques, the performance is expressed in terms of
      smallest difference in electrophoretic mobilities that can be completely
      separated (R = 1.5). The calculations indicate that closest resolvable species
      (DeltaMUmin ) differ by approximately 10(-13) m(2) /Vs and peak capacity (nc ) is
      1000. Published experimental data were compared to these calculated results.

PMID- 24916308
TI  - Msp1: patrolling mitochondria for lost proteins.

PMID- 24916309
TI  - Adrenocorticotropin hormone 1-39 promotes proliferation and differentiation of
      oligodendroglial progenitor cells and protects from excitotoxic and inflammation
      related damage.
AB  - Oligodendroglia (OL) are highly susceptible to damage and, like neurons, are
      terminally differentiated. It is important to protect OL precursors (OPC) because
      they are reservoirs of differentiating cells capable of myelination following
      perinatal insult and remyelination in white matter diseases, including multiple
      sclerosis (MS). Patients with relapsing-remitting MS are commonly treated with
      high-dose corticosteroids (CS) when experiencing an exacerbation.
      Adrenocorticotropin hormone (ACTH), a primary component of another approved MS
      exacerbation treatment, is a melanocortin peptide that stimulates production of
      CS by the adrenals. Melanocortin receptors are also found in the central nervous
      system (CNS) and on immune cells. ACTH is produced within the CNS and may have CS
      independent effects on glia. We found that ACTH 1-39 stimulated proliferation of
      OPC, and to a lesser extent astroglia (AS) and microglia (MG), in rat glial
      cultures. ACTH accelerated differentiation of PDGFRalpha(+) OPC to a later stage
      marked by galactolipid expression and caused greater expansion of OL myelin-like
      sheets compared with untreated cells. Protective effects of ACTH on OPC were
      assessed by treating cultures with selected toxic agents, with or without ACTH.
      At 200 nM, ACTH protected OPC from death induced by staurosporine, glutamate,
      NMDA, AMPA, kainate, quinolinic acid, H2 O2 , and slow NO release, but not
      against kynurenic acid or rapid NO release. These agents and ACTH were not toxic
      to AS or MG. Our findings indicate that ACTH 1-39 provides benefits by increasing
      the number of OPC, accelerating their development into mature OL, and reducing
      OPC death from toxic insults.

PMID- 24916307
TI  - Insulators recruit histone methyltransferase dMes4 to regulate chromatin of
      flanking genes.
AB  - Chromosomal domains in Drosophila are marked by the insulator-binding proteins
      (IBPs) dCTCF/Beaf32 and cofactors that participate in regulating long-range
      interactions. Chromosomal borders are further enriched in specific histone
      modifications, yet the role of histone modifiers and nucleosome dynamics in this
      context remains largely unknown. Here, we show that IBP depletion impairs
      nucleosome dynamics specifically at the promoters and coding sequence of genes
      flanked by IBP binding sites. Biochemical purification identifies the H3K36
      histone methyltransferase NSD/dMes-4 as a novel IBP cofactor, which specifically
      co-regulates the chromatin accessibility of hundreds of genes flanked by
      dCTCF/Beaf32. NSD/dMes-4 presets chromatin before the recruitment of
      transcriptional activators including DREF that triggers Set2/Hypb-dependent H3K36
      trimethylation, nucleosome positioning, and RNA splicing. Our results unveil a
      model for how IBPs regulate nucleosome dynamics and gene expression through
      NSD/dMes-4, which may regulate H3K27me3 spreading. Our data uncover how IBPs
      dynamically regulate chromatin organization depending on distinct cofactors.

PMID- 24916310
TI  - Analysis of DNA methylation of perennial ryegrass under drought using the
      methylation-sensitive amplification polymorphism (MSAP) technique.
AB  - Perennial ryegrass (Lolium perenne), an excellent grass for forage and turf, is
      widespread in temperate regions. Drought is an important factor that limits its
      growth, distribution, and yield. DNA methylation affects gene expression and
      plays an important role in adaptation to adverse environments. In this study, the
      DNA methylation changes in perennial ryegrass under drought stress were assessed
      using methylation-sensitive amplified polymorphism (MSAP). After 15 days of
      drought stress treatment, the plant height was less than half of the control, and
      the leaves were smaller and darker. Genome-wide, a total of 652 CCGG sites were
      detected by MSAP. The total methylation level was 57.67 and 47.39 % in the
      control and drought treatment, respectively, indicating a decrease of 10.28 % due
      to drought exposure. Fifteen differentially displayed DNA fragments in MSAP
      profiles were cloned for sequencing analysis. The results showed that most of the
      genes involved in stress responses. The relative expression levels revealed that
      three demethylated fragments were up-regulated. The expression of a predicted
      retrotransposon increased significantly, changing from hypermethylation to non
      methylation. Although the extent of methylation in two other genes decreased, the
      sites of methylation remained, and the expression increased only slightly. All of
      these results suggested that drought stress decreased the total DNA methylation
      level in perennial ryegrass and demethylation up-regulated related gene
      expressions and that the extent of methylation was negatively correlated with
      expression. Overall, the induced epigenetic changes in genome probably are an
      important regulatory mechanism for acclimating perennial ryegrass to drought and
      possibly other environmental stresses.

PMID- 24916312
TI  - Why do sperm carry RNA? Relatedness, conflict, and control.
AB  - Classically, sperm were seen as transcriptionally inactive vehicles for
      delivering the paternal haplotype to an egg. Yet, it has become apparent that
      sperm also carry thousands of different RNAs, and the functions of most of these
      are unknown. Here, we make four novel suggestions for sperm RNA function. First,
      they could act as relatedness markers facilitating sperm cooperation. Second,
      they could act as paternally imposed suppressors of haploid interests. Third,
      they could act as a nuptial gift, providing the female with resources that entice
      her to fertilise ova using the sperm of the gift-provider. Fourth, they could
      represent the contents of a Trojan horse, delivered by males to manipulate female
      reproduction. We discuss these ideas and suggest how they might be tested. 

PMID- 24916311
TI  - MicroRNAs related polymorphisms and genetic susceptibility to esophageal squamous
      cell carcinoma.
AB  - Esophageal cancer (EC) is the sixth leading cause of cancer-associated death
      worldwide and the incidence and mortality in China are the highest. The single
      nucleotide polymorphisms (SNPs) related to microRNAs could lead to alteration in
      microRNA expression and contribute to the susceptibility of cancer. To evaluate
      the association between microRNA-related SNPs and EC, a case-control study
      including 381 patients with esophageal squamous cell carcinoma (ESCC) and 426
      gender, age-matched controls was carried out to investigate the genetic
      susceptibility of five microRNA-related SNPs (rs2910164 in microRNA-146a,
      rs11614913 in microRNA-196a-2, rs7813 in GEMIN4, rs1595066 and rs16845990 in
      ErbB4) as well as the interactions of gene-gene and gene-environment in the
      development of ESCC. Variant homozygote genotype of rs11614913 in microRNA-196a-2
      and rs1595066 in ErbB4 were significantly associated with reduced ESCC risk
      (OR(adjusted): 0.62, 95 % CI: 0.39-0.99 and OR(adjusted): 0.38, 95 % CI: 0.24
      0.61). The analysis of haplotypes in ErbB4 gene showed significant increased ESCC
      risk in G(rs1595066)C(rs16845990) and G(rs1595066)T(rs16845990) haplotypes
      (OR(adjusted): 1.46, 95 % CI: 1.08-1.99 and OR(adjusted): 1.33, 95 % CI: 1.10
      1.62), and inversely reduced ESCC risk in A(rs1595066)C(rs16845990) and
      A(rs1595066)T(rs16845990) haplotypes with OR (95 % CI) of 0.75 (0.60-0.94) and
      0.65 (0.49-0.86), respectively. These findings suggest that the polymorphisms in
      the microRNA-related genes may affect susceptibility of ESCC in Chinese Han
      population and the gene-gene interactions play vital roles in the progression on
      esophageal cancer. Future studies with larger sample and different ethnic
      populations are required to support and validate our findings.

PMID- 24916313
TI  - Cardiopulmonary exercise testing for the prediction of morbidity risk after
      rectal cancer surgery.
AB  - BACKGROUND: This study investigated the relationship between objectively measured
      physical fitness variables derived by cardiopulmonary exercise testing (CPET) and
      in-hospital morbidity after rectal cancer surgery. METHODS: Patients scheduled
      for rectal cancer surgery underwent preoperative CPET (reported blind to patient
      characteristics) with recording of morbidity (recorded blind to CPET variables).
      Non-parametric receiver operating characteristic (ROC) curves and logistic
      regression were used to assess the relationship between CPET variables and
      postoperative morbidity. RESULTS: Of 105 patients assessed, 95 (72 men) were
      included; ten patients had no surgery and were excluded (3 by choice, 7 owing to
      unresectable metastasis). Sixty-eight patients had received neoadjuvant
      treatment. ROC curve analysis of oxygen uptake (Vo2 ) at estimated lactate
      threshold (theta^L ) and peak Vo2 gave an area under the ROC curve of 0.87 (95
      per cent confidence interval 0.78 to 0.95; P < 0.001) and 0.85 (0.77 to 0.93; P <
      0.001) respectively, indicating that they can help discriminate patients at risk
      of postoperative morbidity. The optimal cut-off points identified were 10.6 and
      18.6 ml per kg per min for Vo2 at theta^L and peak respectively. CONCLUSION: CPET
      can help predict morbidity after rectal cancer surgery.

PMID- 24916316
TI  - Production of folate in oat bran fermentation by yeasts isolated from barley and
      diverse foods.
AB  - AIMS: The focus of the research was to identify yeasts from barley kernels in
      order to study their folate production capability while maintaining high
      viscosity caused by soluble fibres in oat bran fermentation. METHODS AND RESULTS:
      The 65 isolated yeasts were characterized by API carbohydrate utilization tests,
      and assays for extracellular enzyme activities were the following: amylase, beta
      glucanase, cellulase or CMCase, lipase, protease and xylanase. Yeasts were
      identified by partial DNA sequencing of the 25S D1/D2 and ITS1-5.8S-ITS2 regions.
      They belonged to the genera Aureobasidium, Cryptococcus, Pseudozyma and
      Rhodotorula. Folate production was determined from supernatant and cells grown in
      a rich laboratory medium or directly from oat bran solution inoculated with the
      appropriate yeast. Food yeasts, Saccharomyces cerevisiae, Candida milleri,
      Kluyveromyces marxianus and Galactomyces geotrichum, were used for comparison.
      Most of the yeasts isolated from barley destroyed the solid, viscous structure of
      the oat bran solution, indicating that they degraded the viscosity-generating
      soluble fibres, considered to be nutritionally advantageous. The best folate
      producers were S. cerevisiae, followed by Pseudozyma sp., Rhodotorula glutinis
      and K. marxianus. The yeasts maintaining high viscosity were used together with
      lactic acid bacteria (LAB) Streptococcus thermophilus or Lactobacillus rhamnosus
      to ferment oat bran solution. None of the yeasts isolated from barley, contrary
      to S. cerevisiae and C. milleri, produced together with LAB significant amounts
      of folate. CONCLUSIONS: Fermentative yeasts together with LAB are potential for
      use in developing novel high folate content healthy foods and snacks from oat
      bran. SIGNIFICANCE AND IMPACT OF THE STUDY: High soluble fibre content and high
      natural folate content but low energy content food and snack products with
      pleasant fermentation aroma provide possibilities for new developments in the
      food industry.

PMID- 24916317
TI  - Calculation of chemical-shift tensors of heavy nuclei: a DFT/ZORA investigation
      of 199Hg chemical-shift tensors in solids, and the effects of cluster size and
      electronic-state approximations.
AB  - Calculations of the nuclear magnetic resonance chemical-shielding tensors of a
      suite of mercury-containing materials using various cluster models for the
      structures provide a stringent test of the procedures for forming models and for
      calculation with various methods. The inclusion of higher co-ordination shells in
      the molecular clusters permits quantum chemical calculations of (199)Hg chemical
      shielding tensor elements within 3% of the experimental values. We show that it
      is possible to reduce the size of computationally expensive molecular-cluster
      calculations with limited effect on calculated NMR parameters by carefully
      introducing the frozen core approximation. The importance of the relativistic
      Hamiltonian for accurate predictions of chemical-shielding values is demonstrated
      within the molecular cluster approach. The results demonstrate that careful
      design of a cluster to represent the solid-state structure, inclusion of
      relativistic components in the Hamiltonian at least at the spin-orbit level, and
      judicious use of approximations are essential to obtain good agreement with
      experimental results. 

PMID- 24916315
TI  - Human osteoclasts are inducible immunosuppressive cells in response to T cell
      derived IFN-gamma and CD40 ligand in vitro.
AB  - Osteoclasts (OCs) are bone resorbing cells whose activity can be regulated by
      activated T cells and their cytokines. However, the immune function of OCs is
      largely unknown. In this study, we found that as bystanders, human OCs
      effectively suppressed T-cell proliferation induced by allogeneic, microbial
      antigenic, and T-cell receptor stimuli in vitro. Mechanism studies revealed that
      T cell-derived IFN-gamma and CD40 ligand (CD40L) induced the expression of
      indoleamine 2,3-dioxygenase (IDO) in OCs, which mediated the immunosuppressive
      function on T-cell proliferation through depleting tryptophan. Neutralizing IFN
      gamma and blocking CD40L, or silencing or inhibiting IDO in OCs restored T-cell
      proliferation in the presence of OCs. Our data reveal a novel function of human
      OCs as inducible immunosuppressive cells, and a feedback loop between OCs and
      activated T cells. Thus, this study provides new insight into the mechanism of
      the immunosuppressive function of OCs, and may be helpful for developing novel
      therapeutic strategies for human diseases involving both the bone and immune
      systems.

PMID- 24916318
TI  - Evolution and results of the surgical management of 143 cases of severe acute
      pancreatitis in a referral centre.
AB  - INTRODUCTION: Surgery is the accepted treatment for infected acute pancreatitis,
      although mortality remains high. As an alternative, a staged management has been
      proposed to improve results. Initial percutaneous drainage could allow surgery to
      be postponed, and improve postoperative results. Few centres in Spain have
      published their results of surgery for acute pancreatitis. OBJECTIVE: To review
      the results obtained after surgical treatment of acute pancreatitis during a
      period of 12 years, focusing on postoperative mortality. MATERIAL AND METHODS: We
      have reviewed the experience in the surgical treatment of severe acute
      pancreatitis (SAP) at Bellvitge University Hospital from 1999 to 2011. To analyse
      the results, 2 periods were considered, before and after 2005. A descriptive and
      analytical study of risk factors for postoperative mortality was performed
      RESULTS: A total of 143 patients were operated on for SAP, and necrosectomy or
      debridement of pancreatic and/or peripancreatic necrosis was performed, or
      exploratory laparotomy in cases of massive intestinal ischemia. Postoperative
      mortality was 25%. Risk factors were advanced age (over 65 years), the presence
      of organ failure, sterility of the intraoperative simple, and early surgery (< 7
      days). The only risk factor for mortality in the multivariant analysis was the
      time from the start of symptoms to surgery of<7 days; furthermore, 50% of these
      patients presented infection in one of the intraoperative cultures. CONCLUSIONS:
      Pancreatic infection can appear at any moment in the evolution of the disease,
      even in early stages. Surgery for SAP has a high mortality rate, and its delay is
      a factor to be considered in order to improve results.

PMID- 24916319
TI  - Update to the study protocol for a randomized controlled trial comparing
      mindfulness-based cognitive therapy with maintenance anti-depressant treatment
      depressive relapse/recurrence: the PREVENT trial.
AB  - BACKGROUND: Depression is a common and distressing mental health problem that is
      responsible for significant individual disability and cost to society. Medication
      and psychological therapies are effective for treating depression and maintenance
      anti-depressants (m-ADM) can prevent relapse. However, individuals with
      depression often express a wish for psychological help that can help them recover
      from depression in the long-term. A recently developed treatment, mindfulness
      based cognitive therapy (MBCT), shows potential as a brief group program for
      people with recurring depression.This trial asks the policy research question; is
      MBCT with support to taper/discontinue antidepressant medication (MBCT-TS)
      superior to m-ADM in terms of: a primary outcome of preventing depressive
      relapse/recurrence over 24 months; and secondary outcomes of (a) depression free
      days, (b) residual depressive symptoms, (c) antidepressant medication (ADM)
      usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f)
      cost effectiveness? An explanatory research question also asks whether an
      increase in mindfulness skills is the key mechanism of change.The design is a
      single-blind, parallel randomized controlled trial examining MBCT-TS versus m-ADM
      with an embedded process study. To answer the main policy research question the
      proposed trial compares MBCT-TS with m-ADM for patients with recurrent
      depression. Four hundred and twenty patients with recurrent major depressive
      disorder in full or partial remission will be recruited through primary care.
      RESULTS: Depressive relapse/recurrence over two years is the primary outcome
      variable. Analyses will be conducted following CONSORT standards and overseen by
      the trial's Data Monitoring and Safety Committee. Initial analyses will be
      conducted on an intention-to-treat basis, with subsequent analyses being per
      protocol. The explanatory question will be addressed in two mutually informative
      ways: quantitative measurement of potential mediating variables pre- and post
      treatment and a qualitative study of service users' views and experiences.
      CONCLUSIONS: If the results of our exploratory trial are extended to this
      definitive trial, MBCT-TS will be established as an alternative approach to
      maintenance antidepressants for people with a history of recurrent depression.
      The process studies will provide evidence about the effective components which
      can be used to improve MBCT and inform theory as well as other therapeutic
      approaches. TRIAL REGISTRATION: Trial registered 7 May 2009; ISRCTN26666654.

PMID- 24916320
TI  - Ambiguanine A-G, hexahydrobenzophenanthridine alkaloids from Corydalis ambigua
      var. amurensis.
AB  - Seven hexahydrobenzophenanthridine-type alkaloids, Ambiguanine A-G, along with
      eight known alkaloids, were isolated from tubers of Corydalis ambigua var.
      amurensis. Their structures were elucidated based on extensive spectroscopic
      analyses, with absolute configurations determined by CD experiments. 

PMID- 24916321
TI  - Chemical constituents of Abies delavayi.
AB  - Systematic phytochemical investigations on Abies delavayi afforded 110 compounds,
      including 49 terpenoids, 13 lignans, 20 flavonoids, three coumarins, and 25 other
      chemical constituents. By detailed analysis of one- and two-dimensional NMR
      spectroscopic and high-resolution mass spectrometric data, 10 previously
      unreported compounds were identified: they comprised three sesquiterpenoids, two
      diterpenoids, one triterpenoid, one monoterpenoid, one flavonoid, and two
      phenols. These 10 compounds and some previously known ones were subjected to two
      cytotoxic bioassays against three human tumor cell lines and NO production
      inhibition on RAW264.7 macrophages, respectively. (25R)-24,25-Dihydroabieslactone
      had the strongest cytotoxic activity against Colo-205 cells with an IC50 value of
      19.0+/-3.7MUg/mL. (+)-T-cadinol, 8,11,13-abietatrien-15-ol-18-yl acetate, 18
      acetoxy-13-epi-manool, imperatorin, bergapten, and 5,7-O-dimethyl poriol
      exhibited weak inhibitory activity against LPS-induced NO production in RAW264.7
      macrophages with IC50 values of approximately 50MUg/mL. 

PMID- 24916322
TI  - Study on Ag mesh/conductive oxide hybrid transparent electrode for film heaters.
AB  - Ag mesh-indium tin oxide (ITO) hybrid transparent conductive films were
      fabricated and evaluated for use in film heaters. PS monolayer templates were
      prepared using highly mono-dispersed PS spheres (11.2 MUm) obtained by a
      filtering process with micro-sieves. At first, three Ag meshes with different
      sheet resistances (20, 100, and 300 Omega sq(-1)) and transmittances (70, 73, and
      76%) were evaluated for film heaters in terms of voltage and long-term stability.
      Subsequently, in an effort to obtain better transmittance, Ag mesh-ITO hybrid
      heaters were fabricated utilizing finite ITO depositions. At the optimised ITO
      thickness (15 nm), the sheet resistance and the transmittance were 300 Omega sq(
      1) and 88%, respectively, which indicates that this material is a good potential
      candidate for an efficient defroster in vehicles. 

PMID- 24916324
TI  - Rabeprazole-Induced Tinnitus.

PMID- 24916323
TI  - Chronic stress induces steatohepatitis while decreases visceral fat mass in mice.
AB  - BACKGROUND: Prolonged stress leads over time to allostatic load on the body and
      is likely to exacerbate a disease process. Long-term of stress exposure is one of
      a risk factor for metabolism-related diseases such as obesity and type 2
      diabetes. However, the relationship between chronic stress and non-alcoholic
      fatty liver disease (NAFLD) remain unknown. METHODS: To address the hypothesis
      that chronic stress associate to NAFLD development, we subjected C57bl/6 mice to
      electric foot shock and restraint stress for 12 weeks to set up chronic stress
      model. Then the serum and hepatic triglyceride (TG), total cholesterol (TC) were
      measured. Hepatic HE and Oil red O staining were used to specify the state of the
      NAFLD. To investigate whether inflammation takes part in the stress-induced NAFLD
      process, related visceral fat, serum and hepatic inflammatory factors were
      measured. RESULTS: We observed that chronic stress led to an overall increase of
      hepatic triglyceride and cholesterol while decreasing body weight and visceral
      fat mass. Microvesicular steatosis, lobular inflammation and ballooning
      degeneration were seen in stress liver section. This effect was correlated with
      elevated hepatic and serum inflammatory factors. Although the amount of visceral
      fat was decreased in stress group, various adipocytokines were elevated.
      CONCLUSIONS: We showed that chronic stress is associated to NAFLD and chronic
      inflammation in visceral fat, though food intake and visceral fat mass were
      decreased. These results may contribute to better understanding of the mechanism
      from steatosis to steatohepatitis, and propose a novel insight into the
      prevention and treatment of NAFLD.

PMID- 24916325
TI  - Comment on "Dimethyl Fumarate (Tecfidera): A New Oral Agent for Multiple
      Sclerosis"

PMID- 24916327
TI  - Management of failed stress urinary incontinence surgery.
AB  - With the increasing volume of surgery being performed for the treatment of female
      stress urinary incontinence (SUI), especially with the widespread use of
      midurethral slings (MUS), recurrent urinary incontinence is becoming an
      increasingly common condition. Various preoperative and intraoperative factors
      have been associated with failed SUI surgery. Treatment options for failed SUI
      surgery include conservative management and/or surgical management, which include
      pubovaginal sling, MUS, retropubic suspension, periurethral bulking agents, and
      artificial sphincters. The choice of treatment option will depend on the etiology
      of the patient's failure, patient comorbidities, and patient preference.

PMID- 24916328
TI  - Renal transplantation in augmented bladders.
AB  - Not many years ago, children with congenital abnormalities of the lower urinary
      tract or with bladder dysfunction were denied renal transplantation because they
      were considered very high-risk recipients. However, in the past few decades, we
      learned that in children with poorly compliant, low-capacity bladders,
      augmentation cystoplasty (AC) can create a compliant, low-pressure reservoir that
      helps preserve the kidney graft. Although the incidence of symptomatic urinary
      tract infection (UTI) may be greater in pediatric transplant recipients with an
      AC than in those without, UTI is related more to noncompliance with clean
      intermittent catheterization or vesicoureteral reflux to the native kidney or
      graft than to the AC itself, and usually does not lead to impairment of graft
      function. Today, children with a bladder reconstruction may undergo
      transplantation with the same outcome (graft survival and function) as those with
      normal bladders, although there is some possibility of malignant transformation
      in the intestinal segment used to augment the bladder in these patients. 

PMID- 24916329
TI  - Phagocytic function of Kupffer cells in mouse nonalcoholic fatty liver disease
      models: Evaluation with superparamagnetic iron oxide.
AB  - PURPOSE: To evaluate the Kupffer cell (KC) phagocytic function using
      superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) in
      animal models with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND
      METHODS: Mouse NAFLD models with varying severity were created by feeding high
      fat, high-cholesterol (HFHC) diets to ob/ob mice for 3, 6, or 12 weeks. SPIO-MRI
      was performed on a 4.7-T animal scanner in the mouse NAFLD models, in wildtype
      control mouse, and in the NAFLD mice (NAFLD treatment group) that received 6
      weeks of pioglitazone treatment. The relative signal loss (RSL) of the liver was
      measured in each animal to represent the magnitude of SPIO-induced signal loss of
      the liver. Liver samples were analyzed for steatosis, inflammation, fibrosis, and
      the number of SPIO particles and KCs. RESULTS: RSL values of the NAFLD mice
      (range of RSL value, 26.3%-53.8%) seen on SPIO-MRI were significantly lower than
      those of the control mice (67.7%-74.8%, P <= 0.008) and decreased in proportion
      to the duration of their HFHC diet (mean +/- SD, 53.7% +/- 10.9, 44.7% +/- 8.2,
      and 26.3% +/- 12.6, after 3-, 6-, and 12-week HFHC diet, respectively, on 20
      minute delayed images). For the NAFLD treatment group, the RSL values increased
      after 6 weeks of pioglitazone treatment, compared with the values before
      treatment (P <= 0.039). The RSL values had significant independent correlation
      with both hepatic steatosis (P = 0.007) and inflammation (P = 0.023). CONCLUSION:
      KC phagocytic dysfunction is aggravated in the progression of NAFLD and may be
      reversible with therapeutic intervention. SPIO-MRI may be useful for classifying
      the severity of NAFLD and monitoring the treatment response of NAFLD.

PMID- 24916331
TI  - Charged-molecule physics.
AB  - Commonly, chemical modification is considered to be the ultimate way to tune
      properties of graphene for new devices. The work of Riss and colleagues reported
      in this issue of ACS Nano demonstrates a reverse approach that enables tuning of
      molecular properties with graphene. When a back-gate voltage is used, the Fermi
      level of graphene is shifted with respect to the electronic states of the
      molecules. This extra electric field opens fascinating new routes toward ultimate
      sensitive sensors or experimental devices for studying new molecular physics. 

PMID- 24916330
TI  - Metyrapone alleviates deleterious effects of maternal food restriction on lung
      development and growth of rat offspring.
AB  - Maternal food restriction (MFR) causes intrauterine growth restriction, a known
      risk factor for developing chronic lung disease. However, it is unknown whether
      this negative outcome is gender specific or preventable by blocking the MFR
      induced hyperglucocorticoidism. Using a well-established rat model, we used
      metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR
      induced lung changes on postnatal day (p) 21 in a gender-specific manner. From
      embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet
      or a 50% caloric restricted diet with or without MTP supplementation.
      Postnatally, the offspring were fed ad libitum from healthy dams until p21.
      Morphometric, Western blot, and immunohistochemical analysis of the lungs
      demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count,
      decrease in adipogenic protein peroxisome proliferator-activated receptor gamma,
      increase in myogenic proteins (fibronectin, alpha-smooth muscle actin, and
      calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding
      factor 1 and beta-catenin), and increase in glucocorticoid receptor (GR) levels.
      The MFR-induced lung phenotype and the effects of MTP were similar in both
      genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to
      myogenic phenotype, lung fibroblasts were used to independently study the effects
      of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation
      increased myogenic proteins, Wnt signaling intermediates, and GR, all changes
      blocked by protein supplementation. MTP also blocked, likely by normalizing
      nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced
      increase in myogenic proteins, but had no effect on GR levels. In summary,
      protein restriction and increased glucocorticoid levels appear to be the key
      players in MFR-induced lung disease, affecting both genders. 

PMID- 24916332
TI  - The formation of pyrroline and tetrahydropyridine rings in amino acids catalyzed
      by pyrrolysine synthase (PylD).
AB  - The dehydrogenase PylD catalyzes the ultimate step of the pyrrolysine pathway by
      converting the isopeptide L-lysine-Nepsilon-3R-methyl-D-ornithine to the 22nd
      proteinogenic amino acid. In this study, we demonstrate how PylD can be harnessed
      to oxidize various isopeptides to novel amino acids by combining chemical
      synthesis with enzyme kinetics and X-ray crystallography. The data enable a
      detailed description of the PylD reaction trajectory for the biosynthesis of
      pyrroline and tetrahydropyridine rings as constituents of pyrrolysine analogues. 

PMID- 24916333
TI  - Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of
      colorectal tumors in Lynch syndrome: the GEOLynch cohort study.
AB  - PURPOSE: Dietary intake of B vitamins and methionine, essential components of DNA
      synthesis and methylation pathways, may influence colorectal tumor (CRT)
      development. The impact of B vitamins on colorectal carcinogenesis in individuals
      with Lynch syndrome (LS) is unknown but is important given their high lifetime
      risk of developing neoplasms. The role of MTHFR C677T genotype in modifying these
      relationships in LS individuals is also unclear. We investigated associations
      between dietary intakes of folate, vitamins B2, B6, B12, and methionine and CRT
      development in a prospective cohort study of 470 mismatch repair gene mutation
      carriers. METHODS: Dietary intakes were assessed by food frequency questionnaire.
      Cox regression models with robust sandwich covariance estimation, adjusted for
      age, sex, physical activity, number of colonoscopies during person-time, NSAID
      use, and mutual vitamins were used to calculate hazard ratios (HRs) and 95 %
      confidence intervals (95 % CIs). Analyses were also stratified by MTHFR C677T
      genotype. RESULTS: During a median person-time of 28.0 months, 131 persons
      developed a CRT. Fifty-one of these persons developed an incident colorectal
      adenoma, while there were four persons who developed an incident colorectal
      carcinoma. Compared to the lowest tertile of intake, adjusted HRs (95 % CIs) for
      CRT development in the highest tertile were 1.06 (0.59-1.91) for folate, 0.77
      (0.39-1.51) for vitamin B2, 0.98 (0.59-1.62) for vitamin B6, 1.24 (0.77-2.00) for
      vitamin B12, and 1.36 (0.83-2.20) for methionine. Low vitamin B2 and low
      methionine intake were statistically significantly associated with an increased
      risk of CRT in MTHFR 677TT individuals compared to a combined reference of
      persons with low intake and CC genotype. CONCLUSIONS: There was no suggestion
      that intake of any dietary B vitamin or methionine was associated with CRT
      development among those with LS.

PMID- 24916334
TI  - Nanoparticle formulation improves the anticonvulsant effect of clonazepam on the
      pentylenetetrazole-induced seizures: behavior and electroencephalogram.
AB  - To document the efficacy of clonazepam (CLZ) either free as a solution or loaded
      in solid lipid nanoparticles (CLZ-SLN) or mixed micelles (CLZ-MM), the in vitro
      blood-brain barrier permeability of the formulations was determined. Behavior
      and/or electroencephalograms (EEGs) of rodents receiving treatments were also
      studied. The in vitro permeability of CLZ increased when associated with SLN, but
      decreased in the case of MM. The occurrence of the pentylenetetrazole (PTZ)
      induced seizures in mice was significantly prevented by CLZ, even when exposed a
      lower dose of CLZ-SLN after administration by the oral route. The behavioral
      severity and EEGs showing the PTZ-induced paroxystic activity in rats diminished
      significantly in the presence of CLZ alone (0.3 mg/kg), and were almost totally
      prevented in the rats treated with CLZ-SLN (equivalent to 0.3 mg/kg). The
      frequency, duration, and spreading of the spikes-wave of rats treated with CLZ
      SLN decreased significantly as compared with CLZ alone, CLZ-MM, or the vehicle.
      These results show an in vitro-in vivo correlation in the enhanced blood-brain
      barrier permeability of SLN formulation, and a contribution of MM to the carrier
      effect of drugs toward the bloodstream and brain, where this pharmaceutical
      formulation of CLZ-SLN improves the anticonvulsant effect of this benzodiazepine,
      thus offering additional advantages after oral administration.

PMID- 24916335
TI  - Brain differences between persistent and remitted attention deficit hyperactivity
      disorder.
AB  - Previous resting state studies examining the brain basis of attention deficit
      hyperactivity disorder have not distinguished between patients who persist versus
      those who remit from the diagnosis as adults. To characterize the neurobiological
      differences and similarities of persistence and remittance, we performed resting
      state functional magnetic resonance imaging in individuals who had been
      longitudinally and uniformly characterized as having or not having attention
      deficit hyperactivity disorder in childhood and again in adulthood (16 years
      after baseline assessment). Intrinsic functional brain organization was measured
      in patients who had a persistent diagnosis in childhood and adulthood (n = 13),
      in patients who met diagnosis in childhood but not in adulthood (n = 22), and in
      control participants who never had attention deficit hyperactivity disorder (n =
      17). A positive functional correlation between posterior cingulate and medial
      prefrontal cortices, major components of the default-mode network, was reduced
      only in patients whose diagnosis persisted into adulthood. A negative functional
      correlation between medial and dorsolateral prefrontal cortices was reduced in
      both persistent and remitted patients. The neurobiological dissociation between
      the persistence and remittance of attention deficit hyperactivity disorder may
      provide a framework for the relation between the clinical diagnosis, which
      indicates the need for treatment, and additional deficits that are common, such
      as executive dysfunctions.

PMID- 24916336
TI  - A randomized phase II/III trial of perioperative chemotherapy with adriamycin
      plus ifosfamide versus gemcitabine plus docetaxel for high-grade soft tissue
      sarcoma: Japan Clinical Oncology Group Study JCOG1306.
AB  - A randomized Phase II/III trial was planned to commence in March 2014.
      Perioperative chemotherapy with adriamycin plus ifosfamide is the current
      standard treatment for T2bN0M0 high-grade non-round cell soft tissue sarcoma. The
      purpose of this study is to confirm the non-inferiority of perioperative
      chemotherapy with gemcitabine and docetaxel to adriamycin plus ifosfamide for
      patients with T2bN0M0 or any TN1M0 non-round cell soft tissue sarcoma in the
      extremities and body wall. A total of 140 patients will be accrued from 28
      Japanese institutions over 6 years. The primary endpoint in the Phase II part is
      the proportion of completion of pre-operative chemotherapy without progressive
      disease and overall survival in the Phase III part. The secondary endpoints are
      progression-free survival, response rate of pre-operative chemotherapy,
      pathological response rate, proportion of preservation of diseased limbs, disease
      control rate and proportion of adverse events. This trial has been registered in
      the UMIN Clinical Trials Registry as UMIN000013175
      [http://www.umin.ac.jp/ctr/index.htm]. 

PMID- 24916337
TI  - A new middle-range diameter bronchoscope with large channel for transbronchial
      sampling of peripheral pulmonary lesions.
AB  - OBJECTIVE: Although the diagnostic yield of guided bronchoscopy for peripheral
      pulmonary lesions has improved to 70%, it is still low compared with
      transthoracic needle aspiration. We produced a new bronchoscope with middle-range
      diameter and large channel (BF-Y0053, Olympus, Japan), and evaluated its
      diagnostic efficacy for peripheral pulmonary lesions. METHODS: This was a
      retrospective study on 70 consecutive patients with peripheral pulmonary lesions
      who underwent diagnostic bronchoscopy using BF-Y0053 combined with endobronchial
      ultrasound with a guide sheath at the National Cancer Center Hospital from
      September 2013 to November 2013. Diagnostic performance of the procedure was
      analyzed and compared among three groups of peripheral pulmonary lesions:
      'peripheral-small' lesions (<= 30 mm and adjacent to visceral pleura), 'central
      small' lesions (<= 30 mm and not adjacent to the visceral pleura), and 'large'
      lesions (>30 mm). RESULTS: Sixty (85.7%) patients had malignant diseases.
      Diagnosis was established by bronchoscopy in 61 of 70 patients (87.1%); the
      respective yields for 'central-small' and 'large' lesions were significantly
      higher than that for 'peripheral-small' lesions (96.3%, 94.4%, 72%, P = 0.0026).
      This diagnostic accuracy was achieved regardless of other clinical and procedural
      factors such as, lesion size, feature ground glass opacity (or solid),
      endobronchial ultrasound-probe location (within or outside) or operator skill.
      There were no major post-procedural complications. CONCLUSIONS: A new middle
      range diameter bronchoscope with large channel combined with endobronchial
      ultrasound with a guide sheath can enhance the efficacy of transbronchial
      sampling to its maximal potential to diagnose peripheral pulmonary lesions safely
      and accurately, particularly for patients who have tumors away from the visceral
      pleura.

PMID- 24916338
TI  - Years of life lost to incarceration: inequities between Aboriginal and non
      Aboriginal Canadians.
AB  - BACKGROUND: Aboriginal representation in Canadian correctional institutions has
      increased rapidly over the past decade. We calculated "years of life lost to
      incarceration" for Aboriginal and non-Aboriginal Canadians. METHODS:
      Incarceration data from provincial databases were used conjointly with
      demographic data to estimate rates of incarceration and years of life lost to
      provincial incarceration in (BC) and federal incarceration, by Aboriginal status.
      We used the Sullivan method to estimate the years of life lost to incarceration.
      RESULTS: Aboriginal males can expect to spend approximately 3.6 months in federal
      prison and within BC spend an average of 3.2 months in custody in the provincial
      penal system. Aboriginal Canadians on average spend more time in custody than
      their non-Aboriginal counterparts. The ratio of the Aboriginal incarceration rate
      to the non-Aboriginal incarceration rate ranged from a low of 4.28 in
      Newfoundland and Labrador to a high of 25.93 in Saskatchewan. Rates of
      incarceration at the provincial level were highest among Aboriginals in Manitoba
      with an estimated rate of 1377.6 individuals in prison per 100,000 population
      (95% confidence interval [CI]: 1311.8-1443.4). CONCLUSIONS: The results indicate
      substantial differences in life years lost to incarceration for Aboriginal versus
      non-Aboriginal Canadians. In light of on-going prison expansion in Canada, future
      research and policy attention should be paid to the public health consequences of
      incarceration, particularly among Aboriginal Canadians.

PMID- 24916339
TI  - The association between glomerular filtration rate and left ventricular function
      in two independent community-based cohorts of elderly.
AB  - BACKGROUND: The cardiorenal syndrome, the detrimental bi-directional interplay
      between symptomatic heart failure and chronic kidney disease, is a major clinical
      challenge. Nonetheless, it is unknown if this interplay begins already at an
      asymptomatic stage. Therefore we investigated whether the glomerular filtration
      rate (GFR) is associated with left ventricular function in participants free from
      clinical heart failure and with a left ventricular ejection fraction (LVEF) >40%
      and with pre-specified sub-group analyses in individuals with a GFR >60
      mL/min/m(2). METHODS: Two independent community-based cohorts were used; the
      Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911;
      50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men
      (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association
      between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic
      (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left
      ventricular function (myocardial performance index [MPI]) determined by
      echocardiography. RESULTS: In both PIVUS and ULSAM, higher eGFR was significantly
      associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS,
      higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P =
      0.006), in age- and sex-adjusted models. After further adjustment for
      cardiovascular risk factors, the association between higher eGFR and higher LVEF
      was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In
      PIVUS, the age- and sex-adjusted association between eGFR and left ventricular
      function was similar in participants with eGFR >60 mL/min/m(2). CONCLUSIONS: Our
      data suggest that the interplay between kidney and heart function begins prior to
      the development of symptomatic heart failure and kidney disease.

PMID- 24916341
TI  - The presence of benzimidazole resistance mutations in Haemonchus placei from US
      cattle.
AB  - Haemonchus populations were collected from cattle from mid-western and eastern
      Southern US (four and six populations, respectively) to determine the relative
      prevalence of Haemonchus contortus and Haemonchus placei and the frequency of the
      three isotype-1 beta-tubulin polymorphisms associated with benzimidazole
      resistance. A minimum of 32 individual adult worms were genotyped at position 24
      of the rDNA ITS-2 for each population to determine species identity (296 worms in
      total). One population from Georgia was identified as 100% H. contortus with the
      remaining nine populations identified as 100% H. placei. For the H. contortus
      population, 29 out of 32 worms carried the P200Y (TAC) isotype-1 beta-tubulin and
      2 out of 32 worms carried the P167Y (TAC) benzimidazole resistance associated
      polymorphisms respectively. For H. placei, six out of the nine populations
      contained the P200Y (TAC) isotype-1 beta-tubulin benzimidazole resistance
      associated polymorphism at low frequency (between 1.6% and 9.4%) with no
      resistance associated polymorphisms being identified at the P198 and P167 codons.
      This is the first report of the P200Y (TAC) isotype-1 beta-tubulin benzimidazole
      resistance associated polymorphism in H. placei. The presence of this mutation in
      multiple independent H. placei populations indicates the risk of resistance
      emerging in this parasite should benzimidazoles be intensively used for parasite
      control in US cattle. 

PMID- 24916340
TI  - Multi-tissue transcriptomics of the black widow spider reveals expansions, co
      options, and functional processes of the silk gland gene toolkit.
AB  - BACKGROUND: Spiders (Order Araneae) are essential predators in every terrestrial
      ecosystem largely because they have evolved potent arsenals of silk and venom.
      Spider silks are high performance materials made almost entirely of proteins, and
      thus represent an ideal system for investigating genome level evolution of novel
      protein functions. However, genomic level resources remain limited for spiders.
      RESULTS: We de novo assembled a transcriptome for the Western black widow
      (Latrodectus hesperus) from deeply sequenced cDNAs of three tissue types. Our
      multi-tissue assembly contained ~100,000 unique transcripts, of which > 27,000
      were annotated by homology. Comparing transcript abundance among the different
      tissues, we identified 647 silk gland-specific transcripts, including the few
      known silk fiber components (e.g. six spider fibroins, spidroins). Silk gland
      specific transcripts are enriched compared to the entire transcriptome in several
      functions, including protein degradation, inhibition of protein degradation, and
      oxidation-reduction. Phylogenetic analyses of 37 gene families containing silk
      gland specific transcripts demonstrated novel gene expansions within silk glands,
      and multiple co-options of silk specific expression from paralogs expressed in
      other tissues. CONCLUSIONS: We propose a transcriptional program for the silk
      glands that involves regulating gland specific synthesis of silk fiber and glue
      components followed by protecting and processing these components into functional
      fibers and glues. Our black widow silk gland gene repertoire provides extensive
      expansion of resources for biomimetic applications of silk in industry and
      medicine. Furthermore, our multi-tissue transcriptome facilitates evolutionary
      analysis of arachnid genomes and adaptive protein systems.

PMID- 24916342
TI  - Production, purification and therapeutic potential of egg yolk antibodies for
      treating Trypanosoma evansi infection.
AB  - The use of avian antibodies has aroused interest in biomedical research due to
      the numerous advantages compared to mammal's antibodies. Our study aimed to
      produce and purify IgY immunoglobulins in order to use as an alternative therapy
      against Trypanosoma evansi. Every 14 days, four New Hampshire chickens were
      immunized with trypomastigotes of T. evansi, totaling five inoculations. Eggs
      were collected during 70 days and the extraction of IgY was performed by
      precipitation through the PEG-6000 method. Characterization and purification of
      IgY anti-T. evansi were carried out by SDS-PAGE and Western blot, where heavy and
      light chains were detected. The production of IgY was noted during the whole
      period, and the average production was 2.87 +/- 0.14 at the end of this study.
      Sample's titration allowed the quantification of specific IgY anti-T. evansi,
      with antibodies produced showing high avidity indexes. The results indicated that
      T. evansi is able to generate an immune response in poultry, resulting in a
      production of specific antibodies. In vivo test showed that IgY treatment
      resulted in increase of prepatent period, longevity and survival of infected
      animals, when compared with the positive control, demonstrating an initial, but
      no curative, trypanocidal activity.

PMID- 24916343
TI  - Stereocontrolled synthesis of bicyclic sulfamides via Pd-catalyzed alkene
      carboamination reactions. Control of 1,3-asymmetric induction by manipulating
      mechanistic pathways.
AB  - A new annulation strategy for the synthesis of trans-bicyclic sulfamides is
      described. The Pd-catalyzed alkene carboamination reactions of 2-allyl and cis
      2,5-diallyl pyrrolidinyl sulfamides with aryl and alkenyl triflates afford the
      fused bicyclic compounds in good yields and with good diastereoselectivity (up to
      13:1 dr). Importantly, by employing reaction conditions that favor an anti
      aminopalladation mechanism, the relative stereochemistry between the C3 and C4a
      stereocenters of the products is reversed relative to related Pd-catalyzed
      carboamination reactions that proceed via syn-aminopalladation. 

PMID- 24916344
TI  - Deducing the molecular properties of zwitterionic, protonated, deprotonated, and
      double-deprotonated forms of L-cysteine from vibrational spectroscopy (IR, Raman,
      VCD) and quantum chemical calculations.
AB  - The behavior of L-cysteine (C3H7NO2S, (2R)-2-amino-3-sulfanylpropanoic acid) in
      water at different pH values was analyzed both experimentally and theoretically.
      The behavior was studied at pH values of 5.21 (at this pH, L-cysteine is a
      zwitterionic species), 1.00 (protonated species), 8.84 (monodeprotonated
      species), and 13.00 (dideprotonated species). We carried out a vibrational study
      using nonchiroptical (IR-Raman) and chiroptical (VCD) techniques complemented by
      quantum chemical calculations. We adopted a dual strategy, as follows. (i) The
      hybrid density functionals B3LYP and M062X and the ab initio MP2 method were
      employed, with the same 6-311++G (d,p) basis set, in order to characterize the
      relative energies and structures of an extensive set of conformers of L-cysteine.
      The presence of water was included by utilizing the IEF-PCM implicit solvation
      model. (ii) The vibrational analysis was made using a chirality-sensitive using a
      chirality-sensitive technique (VCD) and chirality-insensitive techniques (IR,
      including MIR and FIR, and Raman), especially in aqueous solution. The results
      obtained theoretically and experimentally were compared in order to deduce the
      most stable structures at each pH. Moreover, for the first time, the
      monodeprotonated anion of L-cysteine was detected in aqueous solution by means of
      IR, Raman and vibrational circular dichroism (VCD). Finally, analysis of the low
      frequency region using the IR and Raman techniques was shown to be a very
      important way to understanding the conformational preference of the zwitterionic
      species. 

PMID- 24916345
TI  - A fast and unbiased procedure to randomize ecological binary matrices with fixed
      row and column totals.
AB  - A well-known problem in numerical ecology is how to recombine presence-absence
      matrices without altering row and column totals. A few solutions have been
      proposed, but all of them present some issues in terms of statistical robustness
      (that is, their capability to generate different matrix configurations with the
      same probability) and their performance (that is, the computational effort that
      they require to generate a null matrix). Here we introduce the 'Curveball
      algorithm', a new procedure that differs from existing methods in that it focuses
      rather on matrix information content than on matrix structure. We demonstrate
      that the algorithm can sample uniformly the set of all possible matrix
      configurations requiring a computational effort orders of magnitude lower than
      that required by available methods, making it possible to easily randomize
      matrices larger than 10(8) cells. 

PMID- 24916346
TI  - Medical management of patients with peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is one of the most frequent manifestations of
      atherosclerosis and is associated with atherosclerosis in the coronary and
      carotid arteries, leading to a highly increased incidence of cardiovascular
      events. Major risk factors of PAD are similar to those that lead to
      atherosclerosis in other vascular beds. However, there are differences in the
      power of individual risk factors in the different vascular territories. Cigarette
      smoking and diabetes mellitus represent the greatest risks of PAD. For prevention
      of the progression of PAD and accompanying cardiovascular events similar
      preventative measures are used as in coronary artery disease (CAD). However,
      recent data indicate that there are some differences in the efficacy of drugs
      used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment
      is indicated in virtually all patients with PAD. In spite of the absence of hard
      evidence- based data on the long term efficacy of aspirin, it is still considered
      as a first line treatment and clopidogrel as an effective alternative. The new
      antiplatelet drugs ticagrelol and prasugrel also represent promising options for
      treatment of PAD. Statin therapy is indicated to achieve the target low density
      lipoprotein cholesterol level of <=2.5 mmol/L (100 mg/dL) and there is emerging
      evidence that lower levels are more effective. Statins may also improve walking
      capacity. Antihypertensive treatment is indicated to achieve the goal blood
      pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta
      blockers are acceptable for treatment of hypertension in patients with PAD.
      Diabetic patients with PAD should reduce their glycosylated haemoglobin to <=7%.
      As PAD patients represent the group with the highest risk of atherothrombotic
      events, these patients need the most intensive treatment and elimination of risk
      factors of atherosclerosis. These measures should be as comprehensive as those in
      patients with established coronary and cerebrovascular disease. 

PMID- 24916348
TI  - [Regulatory T cells and NK cells in cancer patients].
AB  - NK cells represent the cells of the immune system most effective for eradication
      of infected or neoplastic cells. Regulatory T cells and the two main subgroups
      thereof-the naturally occurring nTregs and the tumor-associated induced Tregs
      (iTregs)-play an important role in the antitumor immune response in cancer
      patients. The current study explores the intercellular interactions of these
      groups of cells in tumor patients, particularly in head and neck cancer. Critical
      interactions between these cells and the cancer cells could be observed in
      extensive experimental analyses. Firstly, we generated tumor-associated iTregs in
      a specific human culture. Subsequently, various phenotypic and functional
      relationships between these cells, nTregs, NK cells and tumor cells were analyzed
      in an autologous system. Although the activity of naive NK cells was enhanced by
      iTregs in the presence of tumor cells, the cytotoxic function of NK cells
      activated by interleukin-2 was markedly inhibited by iTregs and nTregs. Our group
      was able to document new insights into the complex regulation of human NK cells
      and regulatory T cells in the tumor microenvironment. These new insights may be
      of relevance for an improved understanding of the antitumor immune response and
      the development of immunotherapeutic strategies.

PMID- 24916349
TI  - [New perspectives in skeletal muscle tissue engineering].
AB  - Due to the enormous expansion of knowledge in the fields of stem cell research
      and biomaterials, skeletal muscle tissue engineering represents a rapidly
      developing field of biomedical research. This article provides a general overview
      of skeletal muscle tissue engineering, including a discussion of recent findings
      and future research perspectives. Additionally, the results of myogenic
      differentiation of human mesenchymal stem cells and satellite cells are
      presented. 

PMID- 24916350
TI  - [Water regulation in the cochlea : Do molecular water channels facilitate
      potassium-dependent sound transduction?].
AB  - BACKGROUND: Sound transduction in the cochlea critically depends on the
      circulation of potassium ions (K(+)) along so-called "K(+) recycling routes"
      between the endolymph and perilymph. These K(+) currents generate high ionic and
      osmotic gradients, which potentially impair the excitability of sensory hair
      cells and threaten cell survival in the entire cochlear duct. Molecular water
      channels-aquaporins (AQP)-are expressed in all cochlear supporting cells along
      the K(+) recycling routes; however, their significance for osmotic equilibration
      in cochlear duct cells is unknown. METHODS: The diffusive and osmotic water
      permeabilies of Reissner's membrane, the organ of Corti and the entire cochlear
      duct epithelium were determined. Expression of the potassium channel Kir4.1 and
      the water channel AQP4 in the cochlear duct was investigated by
      immunohistochemistry. RESULTS: The calculated water permeability values indicate
      the extent of AQP-facilitated water flux across the cochlear duct epithelium.
      Immunohistochemically, Kir4.1 and AQP4 were found to colocalize in distinct
      membrane domains of supporting cells along the K(+)-recycling routes. CONCLUSION:
      These observations suggest the presence of a rapid AQP-mediated water exchange
      between the endolymph, the cells of the cochlear duct and the perilymph. The
      subcellular colocalization of Kir4.1 and AQP4 in epithelial supporting cells
      indicates functional coupling of potassium and water flow in the cochlea.
      Finally, this offers an explanation for the hearing impairment observed in
      individuals with mutations in the AQP4 gene.

PMID- 24916351
TI  - [Risk assessment of nanoparticles in consumer products].
AB  - Nanomaterials are not just used in various areas of scientific research, but are
      increasingly found in consumer products. Particularly the cosmetic and textile
      industries, as well as the medical branch benefit from the specific chemical and
      physical properties of nanoparticles (NPs). However, the knowledge base
      concerning the potential health hazards that nanomaterials hold for humans is far
      from complete. NPs mainly enter the organism via the lungs or the
      gastrointestinal tract, where they can accumulate. Transcutaneous penetration is
      most unlikely in the case of healthy skin. Chronic inflammatory reactions of the
      airways are particularly relevant in the context of potential risks to human
      health. Evidence for a geno- and cytotoxic potential of some of the most
      frequently used NPs is available from cell culture and animal experiments.
      Therefore, the risk of NP-induced cancerogenesis cannot be ruled out. Currently
      available nanotoxicological data is partly contradictory, due to differing
      characteristics of the tested substances and variable experimental settings. Long
      term studies using continuous NP exposure in consumer-relevant dosages are
      needed. Additionally, the molecular mechanisms of NP-induced toxicity have to be
      elucidated in detail. 

PMID- 24916352
TI  - [Development of a computed tomography data-based Vibrant Bonebridge viewer].
AB  - BACKGROUND: Because of the anatomy of the mastoid and the size of the actuator,
      positioning of the Vibrant Bonebridge B-FMT can be difficult without prior
      evaluation of the individual computed tomography (CT) scan of the temporal bone.
      Development of a user-friendly CT data viewer to enable positioning of the B-FMT
      in the temporal bone model, whilst identifying individual, potential anatomic
      conflicts and offering possible solutions could provide a useful tool for
      preoperative positioning. OBJECTIVES: Aim of the study was to define the
      requirements of a Vibrant Bonebridge viewer and construct a prototype. MATERIALS
      AND METHODS: Based on a ZIBAmira software version and inclusion of a B-FMT model
      upon creation of a model of the temporal bone-which allows the intuitive
      estimation of individual, anatomic conflicts-a Vibrant Bonebridge viewer was
      constructed. RESULTS: The segmentation time of the individual digital imaging and
      communications in medicine (DICOM) data set is about 5 min. Positioning within
      the individual three-dimensional temporal bone model allows quantitative and
      qualitative estimation of conflicts (sigmoid sinus, middle cranial fossa) and
      determination of a preferred position for the B-FMT. Lifting of the B-FMT can be
      simulated with the help of a virtual washer. CONCLUSION: The Vibrant Bonebridge
      viewer reliably allows simulation of B-FMT positioning. The clinical value of the
      viewer still has to be evaluated.

PMID- 24916353
TI  - [Physiology of the upper esophageal sphincter].
AB  - The upper esophageal sphincter (UES) forms a barrier between the pharynx and the
      esophagus. When opened, the UES allows the food bolus to pass into the esophagus,
      as well as permitting emesis and eructation. The basal sphincter tone constitutes
      a barrier function which serves to prevent reflux and passive aerophagia in the
      case of deep breathing. Basal sphincter tone is dependent on several influencing
      factors; during swallowing, sphincter opening and closure follow a complex
      multiphase pattern. This article presents an overview of the current
      understanding of UES physiology. 

PMID- 24916354
TI  - [Medical examination: Preparation for ENT specialisation : Part 15].

PMID- 24916355
TI  - Hierarchical competition models with Allee effects.
AB  - We consider a two-species hierarchical competition model with a strong Allee
      effect. The Allee effect is assumed to be caused by predator saturation.
      Moreover, we assume that there is a 'silverback' species x that gets first choice
      of the resources and where growth is limited by its own intraspecific
      competition, while the second 'inferior' species y gets whatever is left. Both
      species x and y are assumed to have the property of strong Allee effect. In this
      paper we determine the impact of the presence of the Allee effect on the global
      dynamics of both species. 

PMID- 24916356
TI  - Hepatocellular carcinoma in situs ambiguus: CT findings of a rare disposition.
AB  - Heterotaxic disorders or situs ambiguus are uncommon anatomical variations
      constituted by a partial mirror-image disposition of intra thoracic and/or
      abdominal solid organs. These variations are challenging because rarely met in a
      surgeon's career, and because of the coexistence of numerous other anatomical
      variants, like ones related to the asymmetrical organs, causing difficulties when
      a surgical management is required. We report the case of a 57-year-old patient
      presenting liver cirrhosis in which regular follow-up discovered a hepatocellular
      carcinoma of the right part of the liver associated to numerous anatomical
      variations in the setting of a situs ambiguus. This patient was successfully
      treated by a sub-segmentectomy via a right sub-costal laparotomy. There were
      neither peroperative nor postoperative complications. This case emphasizes the
      technical difficulties faced, successfully managed thanks to a good preoperative
      screening, and allows us to review literature of such a rare and challenging
      situation. 

PMID- 24916357
TI  - Clinical heterogeneity of immunodysregulation, polyendocrinopathy, enteropathy, X
      linked: pulmonary involvement as a non-classical disease manifestation.
AB  - PURPOSE: IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) is
      a rare X-linked recessive life-threatening disorder characterized by autoimmunity
      and early death. Pulmonary complication related with IPEX has not been elucidated
      exactly. Here, we report 4 IPEX patients, 3 of which died from severe pulmonary
      disease. METHODS: Clinical data and laboratory findings including autoantibodies,
      immunoglobulin levels as well as number of T, B and NK cells were evaluated.
      FOXP3 expression and T reg activity were analyzed. The FOXP3 gene was sequenced
      and RNA analysis was performed. RESULTS: Patient I (PI) presented with nephrotic
      syndrome at 3 years of age and then developed autoimmune hepatitis without
      eczema, enteropathy or high IgE and died at 9 years of age due to acute
      respiratory distress syndrome (ARDS). Two cousins of PI had the same hypomorphic
      splice site mutation leading to a deletion of 27 amino acids, but normal FOXP3
      protein expression and normal suppressive capacity of T reg in a proliferation
      inhibition assay. However, they exhibited typical symptoms such as eczema,
      diabetes and enteropathy with eosinophilia at early age (PII, PIII) and were
      transplanted in infancy. One of them had severe respiratory distress right after
      birth (PIII). Patient IV from another family presented with chronic diarrhea
      without autoimmune manifestations and died due to ARDS. CONCLUSION: Lung disease
      related to IPEX syndrome has not been reported before and this entity could be a
      critical factor in disease outcome.

PMID- 24916358
TI  - Interoceptive ability predicts aversion to losses.
AB  - Emotions have been proposed to inform risky decision-making through the influence
      of affective physiological responses on subjective value. The ability to perceive
      internal body states, or "interoception" may influence this relationship. Here,
      we examined whether interoception predicts participants' degree of loss aversion,
      which has been previously linked to choice-related arousal responses.
      Participants performed both a heartbeat-detection task indexing interoception and
      a risky monetary decision-making task, from which loss aversion, risk attitudes
      and choice consistency were parametrically measured. Interoceptive ability
      correlated selectively with loss aversion and was unrelated to the other value
      parameters. This finding suggests that specific and separable component processes
      underlying valuation are shaped not only by our physiological responses, as shown
      in previous findings, but also by our interoceptive access to such signals. 

PMID- 24916359
TI  - Recurrent vitreous hemorrhage associated with regressed retinopathy of
      prematurity in a 47-year-old patient: a case report.
AB  - INTRODUCTION: Vitreous hemorrhage associated with retinopathy of prematurity is
      often seen in childhood, but adult onset without retinal break is rare. We
      describe a case of recurrent vitreous hemorrhage associated with regressed
      retinopathy of prematurity in a 47-year-old patient. CASE PRESENTATION: A 47-year
      old Japanese woman with a history of retinopathy of prematurity presented with a
      visual disturbance in her left eye due to vitreous hemorrhage. Because the
      vitreous hemorrhage was recurrent and refractory, we performed pars plana
      vitrectomy combined with lens extraction by phacoemulsification and intraocular
      lens implantation. No retinal break or retinal detachment was found. No vitreous
      hemorrhage or other complication occurred in the first six months after surgery.
      CONCLUSIONS: Vitrectomy, potentially in combination with lens extraction, should
      be considered in adult-onset recurrent vitreous hemorrhage associated with
      retinopathy of prematurity.

PMID- 24916360
TI  - Validation of the Suicide Resilience Inventory-25 with American and Chinese
      college students.
AB  - This study is the first to evaluate evidence for measurement invariance and the
      psychometric properties of the Suicide Resilience Inventory-25 (SRI-25; Osman et
      al., ) in college-age samples in both the United States and China. We found
      strong support for full measurement invariance of the three-factor structure of
      the SRI-25 in the U.S. (113 men and 238 women) and Chinese (121 men and 205
      women) samples. In addition, we found that the U.S. sample scored significantly
      higher than the Chinese sample on all the individual scale scores. Composite
      scale reliability estimates ranged from moderate (rho = .83) to high (rho = .93)
      across the groups. Although not an aim of the current study, we examined
      estimates of internal consistency of the SRI-25 scales for men and women within
      each sample. Differential correlates of the SRI-25 scales were explored further
      for each sample. These results provide support for the use of the SRI-25 in U.S.
      and Chinese student samples.

PMID- 24916361
TI  - Increasing maternal percentage body fat in early second trimester: a risk factor
      for preeclampsia.
AB  - OBJECTIVE: To determine if maternal percentage body fat (PBF) or fat free mass
      (FFM) in the early second trimester of pregnancy influenced the development of
      preeclampsia. METHODS: A matched nested case-control study was conducted from a
      cohort study of 1668 women at Gansu provincial maternal and child care hospital
      from July 2007 to August 2011 in China. Maternal PBF and FFM were assessed by
      bioelectrical impedance analysis during 12th-16th gestational week. The
      demographic characteristics were all chart abstracted. After childbirth, 70 cases
      of preeclampsia were matched by race/age with 140 uncomplicated pregnancies
      women. Multivariate logistic regression analysis was performed to determine the
      associated risk factors. RESULTS: Pre-pregnancy body mass index were higher in
      women who subsequently developed preeclampsia compared with controls (p < 0.001).
      During 12th-16th gestational week, there were nearly 7-fold increase in the odds
      of preeclampsia (adjusted OR: 6.84, 95% CI: 4.15-41.60) among women with PBF >=
      40% versus women with PBF < 40%. But FFM were not at further increased risk of
      the development of preeclampsia (adjusted OR, 1.02; 95% CI, 0.6-3.6). CONCLUSION:
      Maternal PBF but not FFM is a predictor of preeclampsia in the early second
      trimester. Excessive adipose tissue possibly played an important role in
      developing of preeclampsia.

PMID- 24916362
TI  - Trypanosoma cruzi strain TcI is associated with chronic Chagas disease in the
      Brazilian Amazon.
AB  - BACKGROUND: Chagas disease in the Amazon region is considered an emerging
      anthropozoonosis with a predominance of the discrete typing units (DTUs) TcI and
      TcIV. These DTUs are responsible for cases of acute disease associated with oral
      transmission. Chronic disease cases have been detected through serological
      surveys. However, the mode of transmission could not be determined, or any
      association of chronic disease with a specific T. cruzi DTU's. The aim of this
      study was to characterize Trypanosoma cruzi in patients with chronic Chagas
      disease in the State of Amazonas, Brazil. METHODS: Blood culture and
      xenodiagnosis were performed in 36 patients with positive serology for Chagas
      disease who participated in a serological survey performed in urban and rural
      areas of Manaus, Amazonas. DNA samples were extracted from the feces of
      triatomines used for xenodiagnosis, and the nontranscribed spacer of the mini
      exon gene and the mitochondrial gene cytochrome oxidase subunit II (COII) were
      amplified by PCR and sequenced. RESULTS: Blood culture and xenodiagnosis were
      negative in 100% of samples; however, molecular techniques revealed that in 13
      out of 36 (36%) fecal samples from xenodiagnosis, T. cruzi was characterized as
      the DTU TcI, and different haplotypes were identified within the same DTU.
      CONCLUSION: The DTU TcI, which is mainly associated with acute cases of Chagas
      disease in the Amazon region, is also responsible for chronic infection in
      patients from a region in the State of Amazonas.

PMID- 24916363
TI  - Repeated morphine treatment alters cannabinoid modulation of GABAergic synaptic
      transmission within the rat periaqueductal grey.
AB  - BACKGROUND AND PURPOSE: Cannabinoids and opioids produce antinociception by
      modulating GABAergic synaptic transmission in a descending analgesic pathway from
      the midbrain periaqueductal grey (PAG). While chronic opioid treatment produces
      opioid tolerance, it has recently been shown to enhance cannabinoid-induced
      antinociception within the PAG. This study examined the effect of repeated opioid
      treatment on opioid and cannabinoid presynaptic modulation of GABAergic synaptic
      transmission in PAG. EXPERIMENTAL APPROACH: Midbrain PAG slices were prepared
      from untreated rats, and rats that had undergone repeated morphine or saline
      pretreatment. Whole-cell voltage-clamp recordings were made from neurons within
      the ventrolateral PAG. KEY RESULTS: In slices from untreated animals, the
      cannabinoid receptor agonist WIN55212 and the MU receptor agonist DAMGO inhibited
      electrically evoked GABAA receptor-mediated inhibitory postsynaptic currents
      (IPSCs) IPSCs in PAG neurons, with IC50 s of 30 and 100 nM respectively. The
      inhibition of evoked IPSCs produced by WIN55212 (30 nM) and DAMGO (100 nM) was
      similar in PAG neurons from morphine- and saline-treated animals. The cannabinoid
      CB1 receptor antagonist AM251 increased the frequency of spontaneous miniature
      IPSCs in PAG neurons from repeated morphine-, but not saline-treated animals.
      DAMGO inhibition of evoked IPSCs was enhanced in the presence of AM251 in
      morphine-, but not saline-treated animals. CONCLUSIONS AND IMPLICATIONS: These
      results indicate that the efficiency of agonist-induced inhibition of GABAergic
      synaptic transmission is enhanced by morphine treatment, although this is
      dampened by endocannabinoid-mediated tonic inhibition. Thus, endocannabinoid
      modulation of synaptic transmission could provide an alternative analgesic
      approach in a morphine-tolerant state. LINKED ARTICLES: This article is part of a
      themed section on Opioids: New Pathways to Functional Selectivity. To view the
      other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue
      2.

PMID- 24916364
TI  - Temporary hemiepiphysiodesis of the distal medial femur: MPFL in danger.
AB  - INTRODUCTION: Temporary hemiepiphysiodesis (TH) with plate fixation is a well
      accepted and common treatment for correcting leg malalignment in skeletally
      immature patients. The purpose of this study was to investigate any soft tissue
      damage caused during TH at the distal medial femur with a plate and two screws.
      We hypothesized that correct plate placement can affect the integrity of the
      medial stabilizing structures of the knee, especially the medial patellofemoral
      ligament (MPFL), the medial collateral ligament (MCL) or result in arthrotomy of
      the knee joint itself. MATERIALS AND METHODS: In eight cadaveric knees of five
      adult humans a TH was performed with a plate and two cancellous screws at the
      distal medial femur using a standardized surgical technique. Subsequently the
      medial capsular and ligamentous structures were systematically exposed and
      assessed. Capsular and synovial tissue was also inspected for impingement by the
      plate or screws. RESULTS: In all knees the MPFL was present. In two specimens the
      MPFL was intact and the plate was lying over the dorsal part of the MPFL close to
      the MCL. The MPFL was completely cut in two cases in the central part of the
      ligament. In four cases the MPFL was partially dissected or perforated by a screw
      and fixed to the femur by the plate. The MCL was intact and not impinged by the
      implant in any case. In total four of eight knees the capsule was transected or
      perforated by a screw or by a part of the plate, resulting in intraarticular
      implant placement. CONCLUSIONS: Standard plate placement during TH on the distal
      medial femur frequently leads to damage to the MPFL, impingement of the MPFL, the
      capsular and synovial tissues or exposure of the knee joint.

PMID- 24916365
TI  - Impact of TREM-2 gene silencing on inflammatory response of endotoxin-induced
      acute lung injury in mice.
AB  - Acute lung injury (ALI) is one of the critical clinical respiratory diseases, of
      which infection is the main cause and the first risk factor. This study
      investigated the impact of triggering receptor of myeloid cells expression (TREM)
      2 gene silencing on inflammatory response of endotoxin-induced ALI in mice.
      Lentivirus-mediated TREM-2-shRNA was transfected into healthy male C57BL/6 mice,
      and the lipopolysaccharide-induced ALI model was established. The
      immunohistochemistry, immunofluorescence, fluorescence quantitative PCR, western
      blot, and ELISA were applied to detect the pathological changes of lung tissue
      and expressions of TREM-2, tumor necrosis factor-alpha (TNF-alpha), and
      interleukin 10 (IL-10) in bronchoalveolar lavage fluid. The lentivirus group,
      saline control group, ALI model group, blank control group, and negative control
      group were set up at the same time. Results found that, in lentivirus group, the
      pathological change of lung tissue was significantly lighter than ALI model group
      (P < 0.05), and the expression of TREM-2 was significantly reduced compared with
      all control groups (P < 0.05). The levels of TNF-alpha and IL-10 were
      significantly increased than all control groups (P < 0.05), while above indexes
      in negative control group and blank control group showed no significant
      difference with ALI group (P > 0.05). This study indicates that TREM-2 has a
      protective effect on inflammatory response of endotoxin-induced ALI in mice,
      which has provided new potential targets for prevention and treatment of ALI.

PMID- 24916366
TI  - EOLA1 protects lipopolysaccharide induced IL-6 production and apoptosis by
      regulation of MT2A in human umbilical vein endothelial cells.
AB  - Endothelial cell (EC) injury or dysfunction is believed to be mediated at least
      in part by lipopolysaccharide (LPS). Recent studies have shown that LPS induces
      apoptosis in different types of endothelium, including HUVEC. Previously we used
      EOLA1 (endothelial-overexpressed LPS-associated factor 1) cDNA as a bait and
      performed a yeast two-hybrid screening of a human liver cDNA library and
      identified metallothionein 2a (MT2a) as the associated protein. EOLA1 protein
      plays a role as a signal transduction factor. But the mechanism of EOLA1 mediated
      the protection of cell production of IL-6 and apopotosis in HUVEC is not known.
      MT2a is expressed in many kinds of cells and plays a role in inflammation. In
      this study, we demonstrated that LPS could induce EOLA1 expression in time
      dependent and apparently contributed to the inhibition of IL-6 production and
      apoptosis induced by LPS treatment. We also found that deletion of EOLA1 promoted
      IL-6 production and apoptosis in the treatment of LPS in HUVEC. Furthermore, we
      demonstrated that MT2a was activated by LPS, and played a key role in LPS-induced
      IL-6 expression in HUVEC. We further provided the evidence that EOLA1 functioned
      as a negative regulator for LPS response by regulation of MT2a. These findings
      suggest that EOLA1 may have an important regulatory role during EC inflammatory
      responses. 

PMID- 24916367
TI  - Modeling and analysis of a density-dependent stochastic integral projection model
      for a disturbance specialist plant and its seed bank.
AB  - In many plant species dormant seeds can persist in the soil for one to several
      years. The formation of these seed banks is especially important for disturbance
      specialist plants, as seeds of these species germinate only in disturbed soil.
      Seed movement caused by disturbances affects the survival and germination
      probability of seeds in the seed bank, which subsequently affect population
      dynamics. In this paper, we develop a stochastic integral projection model for a
      general disturbance specialist plant-seed bank population that takes into account
      both the frequency and intensity of random disturbances, as well as vertical seed
      movement and density-dependent seedling establishment. We show that the
      probability measures associated with the plant-seed bank population converge
      weakly to a unique measure, independent of initial population. We also show that
      the population either persists with probability one or goes extinct with
      probability one, and provides a sharp criteria for this dichotomy. We apply our
      results to an example motivated by wild sunflower (Helianthus annuus)
      populations, and explore how the presence or absence of a "storage effect"
      impacts how a population responds to different disturbance scenarios. 

PMID- 24916368
TI  - Are the antagonists of the renin-angiotensin system also anticancer agents?
AB  - The antagonists of the renin-angiotensin system (RAS) have gained increasing
      popularity in the last two decades due to their indisputable efficacy in a number
      of cardiovascular disorders, coupled with an unsurpassed tolerability. However
      some years ago a partial and non-predefined meta-analysis raised the possibility
      that angiotensin receptor antagonists in particular may increase the incidence of
      cancer. This observation, although not confirmed by subsequent, larger analyses,
      caused a remarkable and understandable concern even outside the medical
      community. Herein we will summarize the available evidence pro and con the
      hypothesis of a carcinogenetic activity of RAS antagonists coming to the
      conclusion that these drugs may actually exert an anticancer action. 

PMID- 24916369
TI  - Anterior cervical hypertrichosis: a case report and review of the literature.
AB  - Anterior cervical hypertrichosis (ACH), or "hairy throat," is a rare form of
      localized hypertrichosis that refers to the presence of a tuft of terminal hair
      on the anterior neck. Only 40 cases of ACH have been reported in the literature.
      Although it is usually an isolated finding, it may be associated with systemic
      disorders such as neurologic abnormalities (peripheral neuropathy, developmental
      delay, mental retardation), ophthalmologic disorders (optic atrophy,
      chorioretinal changes), hallux valgus, and dorsal hypertrichosis. Thus it is
      strongly advised to take a thorough family history and to perform clinical
      examinations and investigations (neurologic and ophthalmologic examination,
      electromyography, X-ray of the feet) in all patients with ACH to exclude possible
      associated abnormalities. We report the case of a 7-year-old Italian girl who
      presented with this condition as an isolated finding. 

PMID- 24916370
TI  - Social barriers to Type 2 diabetes self-management: the role of capital.
AB  - Approaches to self-management traditionally focus upon individual capacity to
      make behavioural change. In this paper, we use Bourdieu's concepts of habitus and
      capital to demonstrate the impact of structural inequalities upon chronic illness
      self-management through exploring findings from 28 semi-structured interviews
      conducted with people from a lower socioeconomic region of Adelaide, South
      Australia who have type 2 diabetes. The data suggests that access to capital is a
      significant barrier to type 2 diabetes self-management. While many participants
      described having sufficient cultural capital to access and assess health
      information, they often lacked economic capital and social capital in the form of
      support networks who promote health. Participants were often involved in social
      networks in which activities which are contrary to self-management have symbolic
      value. As a consequence, they entered relationships with health professionals at
      a disadvantage. We conclude that structural barriers to self-management arising
      from habitus resulting in the performance of health behaviours rooted in cultural
      and class background and limited access to capital in the form of economic
      resources, social networks, health knowledge and prestige may have a negative
      impact on capacity for type 2 diabetes self-management. 

PMID- 24916371
TI  - The effect of communication change on long-term reductions in child exposure to
      conflict: impact of the promoting strong African American families (ProSAAF)
      program.
AB  - African American couples (n = 331) with children, 89% of whom were married, were
      assigned to either (a) a culturally sensitive couple- and parenting-enhancement
      program (ProSAAF) or (b) an information-only control condition in which couples
      received self-help materials. Husbands averaged 41 years of age and wives
      averaged 39 years. We found significant effects of program participation in the
      short term on couple communication, which was targeted by the intervention, as
      well as over the long term, on self-reported arguing in front of children. Long
      term parenting outcomes were fully mediated by changes in communication for
      wives, but not for husbands. For husbands, positive change depended on amount of
      wife reported change. We conclude that wives' changes in communication from
      baseline to posttest may be more pivotal for the couples' long-term experience of
      decreased arguing in front of children than are husbands' changes, with wives'
      changes leading to changes in both partners' reports of arguments in front of
      children. 

PMID- 24916372
TI  - Use of tool sets by chimpanzees for multiple purposes in Moukalaba-Doudou
      National Park, Gabon.
AB  - We report our recent findings on the use of tool sets by chimpanzees in Moukalaba
      Doudou National Park, Gabon. Direct observations and evidences left by
      chimpanzees showed that chimpanzees used sticks as pounders, enlargers, and
      collectors to extract honey from beehives of stingless bees (Meliponula sp.),
      which may correspond to those previously found in the same site for fishing
      termites and to those found in Loango National Park, Gabon. However, we observed
      chimpanzees using a similar set of tools for hunting a medium-sized mammal
      (possibly mongoose) that hid inside a log. This is the first report of hunting
      with tools by a chimpanzee population in Central Africa. Chimpanzees may
      recognize the multiple functions and applicability of tools (extracting honey and
      driving prey), although it is still a preliminary speculation. Our findings may
      provide us a new insight on the chimpanzee's flexibility of tool use and
      cognitive abilities of complex food gathering. 

PMID- 24916373
TI  - Abstracts of the 60th Annual Meeting of the Scientific and Standardization
      Committee of the International Society on Thrombosis and Haemostasis, june 23-26,
      2014, Milwaukee, WI.

PMID- 24916374
TI  - The feasibility and clinical efficacy of intravenous iron administration for
      preoperative anaemia in patients with colorectal cancer.
AB  - AIM: The study aimed to analyse the feasibility and efficacy of administration of
      a single intravenous iron infusion (IVI) in the preoperative optimization of
      colorectal cancer patients with anaemia. METHOD: Twenty patients were recruited
      at least 14 days before the planned date of surgery. A single 1000 mg dose of
      ferric carboxymaltose (Ferinject) was administered as an outpatient procedure.
      Blood samples were taken at recruitment prior to drug administration (REC), on
      the day of surgery prior to any intervention (DOS) and on the first postoperative
      day. Allogeneic red blood cell transfusions (ARBT) and outcomes were recorded
      from recruitment throughout the study period. RESULTS: There was a significant
      median rise in haemoglobin levels (Hb) from REC to DOS of 1.8 g/dl [interquartile
      range (IQR) 0.75-2.45, P < 0.001] for the entire cohort. Two patients received
      ARBT preoperatively, and for those not transfused preoperatively (n = 18), this
      incremental Hb rise remained significant (P < 0.001, median 1.65 g/dl, IQR 0.5
      2.3). Of these patients, those who responded to IVI had higher erythropoietin
      (EPO) levels at recruitment (P < 0.01) and lower recruitment Hb values,
      transferrin-saturation (TSAT) and C-reactive protein (CRP) levels (P < 0.05). REC
      Hb (Rs = -0.62, P < 0.01), REC TSAT levels (Rs = -0.67, P < 0.01) and REC EPO (Rs
      = 0.69, P < 0.01) correlated with the magnitude of treatment change in Hb levels.
      Five patients received ARBT until the fourth postoperative day, which was
      significantly fewer than predicted (P < 0.05). CONCLUSION: IVI can be
      administered preoperatively in the outpatient clinic to colorectal cancer
      patients with anaemia, with associated reduction in ARBT use and increase in Hb
      levels.

PMID- 24916375
TI  - Human skin color is influenced by an intergenic DNA polymorphism regulating
      transcription of the nearby BNC2 pigmentation gene.
AB  - Single nucleotide polymorphisms (SNPs) found to be statistically significant when
      associated with human diseases, and other phenotypes are most often located in
      non-coding regions of the genome. One example is rs10765819 located in the first
      intron of the BNC2 gene previously associated with (saturation of) human skin
      color. Here, we demonstrate that a nearby intergenic SNP (rs12350739) in high
      linkage disequilibrium with rs10756819 is likely the causal DNA variant for the
      observed BNC2 skin color association. The highly conserved region surrounding
      rs12350739 functions as an enhancer element regulating BNC2 transcription in
      human melanocytes, while the activity of this enhancer element depends on the
      allelic status of rs12350739. When the rs12350739-AA allele is present, the
      chromatin at the region surrounding rs12350739 is inaccessible and the enhancer
      element is only slightly active, resulting in low expression of BNC2,
      corresponding with light skin pigmentation. When the rs12350739-GG allele is
      present however, the chromatin at the region surrounding rs12350739 is more
      accessible and the enhancer is active, resulting in a higher expression of BNC2,
      corresponding with dark skin pigmentation. Overall, we demonstrate the
      identification of the functional DNA variant that explains the BNC2 skin color
      association signal, providing another important step towards further
      understanding human pigmentation genetics beyond statistical association. We thus
      deliver a clear example of how an intergenic non-coding DNA variant modulates the
      regulatory potential of the enhancer element it is located within, which in turn
      results in allele-dependent differential gene expression affecting variation in
      common human traits. 

PMID- 24916376
TI  - Extensive investigation of the IGF2/H19 imprinting control region reveals novel
      OCT4/SOX2 binding site defects associated with specific methylation patterns in
      Beckwith-Wiedemann syndrome.
AB  - Isolated gain of methylation (GOM) at the IGF2/H19 imprinting control region 1
      (ICR1) accounts for about 10% of patients with BWS. A subset of these patients
      have genetic defects within ICR1, but the frequency of these defects has not yet
      been established in a large cohort of BWS patients with isolated ICR1 GOM. Here,
      we carried out a genetic analysis in a large cohort of 57 BWS patients with
      isolated ICR1 GOM and analyzed the methylation status of the entire domain. We
      found a new point mutation in two unrelated families and a 21 bp deletion in
      another unrelated child, both of which were maternally inherited and affected the
      OCT4/SOX2 binding site in the A2 repeat of ICR1. Based on data from this and
      previous studies, we estimate that cis genetic defects account for about 20% of
      BWS patients with isolated ICR1 GOM. Methylation analysis at eight loci of the
      IGF2/H19 domain revealed that sites surrounding OCT4/SOX2 binding site mutations
      were fully methylated and methylation indexes declined as a function of distance
      from these sites. This was not the case in BWS patients without genetic defects
      identified. Thus, GOM does not spread uniformly across the IGF2/H19 domain,
      suggesting that OCT4/SOX2 protects against methylation at local sites. These
      findings add new insights to the mechanism of the regulation of the ICR1 domain.
      Our data show that mutations and deletions within ICR1 are relatively common.
      Systematic identification is therefore necessary to establish appropriate genetic
      counseling for BWS patients with isolated ICR1 GOM. 

PMID- 24916377
TI  - Gene expression in mdx mouse muscle in relation to age and exercise: aberrant
      mechanical-metabolic coupling and implications for pre-clinical studies in
      Duchenne muscular dystrophy.
AB  - Weakness and fatigability are typical features of Duchenne muscular dystrophy
      patients and are aggravated in dystrophic mdx mice by chronic treadmill exercise.
      Mechanical activity modulates gene expression and muscle plasticity. Here, we
      investigated the outcome of 4 (T4, 8 weeks of age) and 12 (T12, 16 weeks of age)
      weeks of either exercise or cage-based activity on a large set of genes in the
      gastrocnemius muscle of mdx and wild-type (WT) mice using quantitative real-time
      PCR. Basal expression of the exercise-sensitive genes peroxisome-proliferator
      receptor gamma coactivator 1alpha (Pgc-1alpha) and Sirtuin1 (Sirt1) was higher in
      mdx versus WT mice at both ages. Exercise increased Pgc-1alpha expression in WT
      mice; Pgc-1alpha was downregulated by T12 exercise in mdx muscles, along with
      Sirt1, Ppargamma and the autophagy marker Bnip3. Sixteen weeks old mdx mice
      showed a basal overexpression of the slow Mhc1 isoform and Serca2; T12 exercise
      fully contrasted this basal adaptation as well as the high expression of
      follistatin and myogenin. Conversely, T12 exercise was ineffective in WT mice.
      Damage-related genes such as gp91-phox (NADPH-oxidase2), Tgfbeta, Tnfalpha and c
      Src tyrosine kinase were overexpressed in mdx muscles and not affected by
      exercise. Likewise, the anti-inflammatory adiponectin was lower in T12-exercised
      mdx muscles. Chronic exercise with minor adaptive effects in WT muscles leads to
      maladaptation in mdx muscles with a disequilibrium between protective and
      damaging signals. Increased understanding of the pathways involved in the altered
      mechanical-metabolic coupling may help guide appropriate physical therapies while
      better addressing pharmacological interventions in translational research. 

PMID- 24916378
TI  - Loss of TFB1M results in mitochondrial dysfunction that leads to impaired insulin
      secretion and diabetes.
AB  - We have previously identified transcription factor B1 mitochondrial (TFB1M) as a
      type 2 diabetes (T2D) risk gene, using human and mouse genetics. To further
      understand the function of TFB1M and how it is associated with T2D, we created a
      beta-cell-specific knockout of Tfb1m, which gradually developed diabetes. Prior
      to the onset of diabetes, beta-Tfb1m(-/-) mice exhibited retarded glucose
      clearance owing to impaired insulin secretion. beta-Tfb1m(-/-) islets released
      less insulin in response to fuels, contained less insulin and secretory granules
      and displayed reduced beta-cell mass. Moreover, mitochondria in Tfb1m-deficient
      beta-cells were more abundant with disrupted architecture. TFB1M is known to
      control mitochondrial protein translation by adenine dimethylation of 12S
      ribosomal RNA (rRNA). Here, we found that the levels of TFB1M and mitochondrial
      encoded proteins, mitochondrial 12S rRNA methylation, ATP production and oxygen
      consumption were reduced in beta-Tfb1m(-/-) islets. Furthermore, the levels of
      reactive oxygen species (ROS) in response to cellular stress were increased
      whereas induction of defense mechanisms was attenuated. We also show increased
      apoptosis and necrosis as well as infiltration of macrophages and CD4(+) cells in
      the islets. Taken together, our findings demonstrate that Tfb1m-deficiency in
      beta-cells caused mitochondrial dysfunction and subsequently diabetes owing to
      combined loss of beta-cell function and mass. These observations reflect
      pathogenetic processes in human islets: using RNA sequencing, we found that the
      TFB1M risk variant exhibited a negative gene-dosage effect on islet TFB1M mRNA
      levels, as well as insulin secretion. Our findings highlight the role of
      mitochondrial dysfunction in impairments of beta-cell function and mass, the
      hallmarks of T2D. 

PMID- 24916379
TI  - Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to
      phosphorylate and inhibit FOXO1, and promotes neuron survival.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a complex kinase and mutations in LRRK2
      are perhaps the most common genetic cause of Parkinson's disease (PD). However,
      the identification of the normal physiological function of LRRK2 remains elusive.
      Here, we show that LRRK2 protects neurons against apoptosis induced by the
      Drosophila genes grim, hid and reaper. Genetic dissection reveals that Akt is the
      critical downstream kinase of LRRK2 that phosphorylates and inhibits FOXO1, and
      thereby promotes survival. Like human LRRK2, Drosophila lrrk also promotes neuron
      survival; lrrk loss-of-function mutant displays reduced cell numbers, which can
      be rescued by LRRK2 expression. Importantly, LRRK2 G2019S and LRRK2 R1441C
      mutants impair the ability of LRRK2 to activate Akt, and fail to prevent
      apoptotic death. Ectopic expression of a constitutive active form of Akt hence is
      sufficient to rescue this functional deficit. These data establish that LRRK2 can
      protect neurons from apoptotic insult through a survival pathway in which LRRK2
      signals to activate Akt, and then inhibits FOXO1. These results might indicate
      that a LRRK-Akt therapeutic pathway to promote neuron survival and to prevent
      neurodegeneration in Parkinson's disease. 

PMID- 24916380
TI  - New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol
      dehydrogenase RDH11.
AB  - Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies
      that occur in both non-syndromic and syndromic forms, is caused by mutations in
      ~100 genes. Although recent advances in next-generation sequencing have aided in
      the discovery of novel RP genes, a number of the underlying contributing genes
      and loci remain to be identified. We investigated three siblings, born to
      asymptomatic parents of Italian-American descent, who each presented with
      atypical RP with systemic features, including facial dysmorphologies, psychomotor
      developmental delays recognized since early childhood, learning disabilities and
      short stature. RP-associated ophthalmological findings included salt-and-pepper
      retinopathy, attenuation of the arterioles and generalized rod-cone dysfunction
      as determined by almost extinguished electroretinogram in 2 of 3 siblings.
      Atypical for RP features included mottled macula at an early age and
      peripapillary sparing of the retinal pigment epithelium. Whole-exome sequencing
      data, queried under a recessive model of inheritance, identified compound
      heterozygous stop mutations, c.C199T:p.R67* and c.C322T:p.R108*, in the retinol
      dehydrogenase 11 (RDH11) gene, resulting in a non-functional protein, in all
      affected children. In summary, deleterious mutations in RDH11, an important
      enzyme for vision-related and systemic retinoic acid metabolism, cause a new
      syndrome with RP. 

PMID- 24916381
TI  - Analysis of adult cerebral cortex and hippocampus transcriptomes reveals unique
      molecular changes in the Ts1Cje mouse model of down syndrome.
AB  - We investigated gene expression and functional differences between Ts1Cje mice
      and wild-type (WT) littermates in adult cerebral cortex and hippocampus. These
      two brain regions are affected in people with Down syndrome, but have not been
      previously molecularly characterized in Ts1Cje mice. Total RNA was prepared from
      the brains of 8-10-week-old Ts1Cje mice (n = 6) and WT littermates (n = 5) and
      hybridized to Affymetrix 1.0 ST gene mouse arrays. Differentially regulated genes
      were identified and used to perform in silico functional analyses to better
      characterize dysregulated pathways in both brain regions. Hippocampus had more
      significantly differentially expressed genes compared with cortex (30 vs. 7 at a
      Benjamini-Hochberg false discovery rate of 20%). We identified novel genes that
      were differentially regulated in adult brains, including Cyb5r1, Fsbp, Vmn2r110,
      Snd1 and Zhx2. Functional analyses in Ts1Cje mice highlighted the importance of
      NFAT signaling, oxidative stress, neuroinflammation and olfactory perception via
      G-protein signaling. In a comparison of adult Ts1Cje and WT brains, we identified
      new genes and pathway differences in the cortex and hippocampus. Our analyses
      identified physiologically relevant pathways that can serve as targets for the
      development of future treatments to improve neurocognition in Down syndrome. 

PMID- 24916382
TI  - Utilization of cross-matched or HLA-matched platelets for patients refractory to
      platelet transfusion.
AB  - BACKGROUND: Use of cross matching or HLA matching for donor selection is the
      basis of managing patients refractory to platelet (PLT) transfusion. Because of
      changes in patient care, we evaluated the effect of cross matching and HLA
      matching in patients refractory to PLT transfusion. STUDY DESIGN AND METHODS: We
      identified all patients who received either HLA-matched or cross-matched PLTs
      during a 3-year period at our medical center. Patient records were reviewed and
      laboratory data were collected. One- to 4-hour corrected count increments (CCIs)
      were calculated for transfusions given up to 72 hours before receiving these
      specialized units and the HLA-matched or cross-matched units themselves. RESULTS:
      Thirty-two patients were identified who received a total of 354 PLT transfusions.
      Of these, 161 were from unselected apheresis, 152 were cross matched, and 41 were
      HLA selected. The median CCI for random-donor transfusions was 0 (range, 0 *
      10(9)-10.5 * 10(9)/L), for cross-matched PLT transfusions 1.7 * 10(9)/L (0 *
      10(9)-5.1 * 10(9)/L), and for HLA-matched transfusions 1.2 * 10(9)/L (0 * 10(9)
      13.9 * 10(9)/L). Only 25 and 30% of cross-match-compatible or HLA-selected units,
      respectively, gave 1- to 4-hour CCIs of more than 5.0 * 10(9)/L compared to 12%
      of the transfusions from random donors. There were no significant differences in
      the 1- to 4-hour CCIs when comparing random units with HLA-selected or cross
      match-compatible units. There was also no significant difference when comparing
      the HLA-matched and cross-match-compatible PLT units with each other.
      CONCLUSIONS: The use of cross-match-compatible or HLA-matched units did not
      provide better increments in PLT count when compared to random nonselected units.
      Clinical factors may overpower immunologic matching.

PMID- 24916383
TI  - Mirincamycin, an old candidate for malaria combination treatment and prophylaxis
      in the 21st century: in vitro interaction profiles with potential partner drugs
      in continuous culture and field isolates.
AB  - BACKGROUND: Spreading resistance of Plasmodium falciparum to existing drugs calls
      for the search for novel anti-malarial drugs and combinations for the treatment
      of falciparum malaria. METHODS: In vitro and ex vivo investigations were
      conducted with fresh P. falciparum field isolates and culture-adapted P.
      falciparum clones to evaluate the anti-malarial potential of mirincamycin, a
      lincosamide, alone and in combination with tafenoquine (TQ), dihydroartemisinin
      (DHA), and chloroquine (CQ). All samples were tested in a histidine-rich protein
      2 (HRP2) drug susceptibility assay. RESULTS: Interaction analysis showed additive
      to synergistic interaction profiles with these potential partner drugs, with an
      overall geometric mean fractional inhibitory concentration at 50% inhibition
      (FIC50) of 0.78, 0.80 and 0.80 for mirincamycin with TQ, DHA, and CQ,
      respectively. Antagonism was not found in any of the tested field isolates or
      clones. The strongest tendency toward synergy (i.e. the lowest FIC) was seen with
      a combination ratio of 1:0.27 to 1:7.2 (mean 1:2.7) for the combination with
      tafenoquine. The optimal combination ratios for DHA and CQ were 1:444.4 to
      1:36,000 (mean 1:10,755.5) and 1:2.7 to 1:216 (mean 1:64.5), respectively. No
      evidence of an activity correlation (i.e. potential cross-resistance) with DHA,
      mefloquine, quinine or chloroquine was seen whereas a significant correlation
      with the activity of clindamycin and azithromycin was detected. CONCLUSIONS:
      Mirincamycin combinations may be promising candidates for further clinical
      investigations in the therapy and prophylaxis of multidrug-resistant falciparum
      malaria or in combination with 4 or 8-aminoquinolines for the treatment and
      relapse prevention of vivax malaria.

PMID- 24916384
TI  - Ciclosporin therapy for canine generalized discoid lupus erythematosus refractory
      to doxycycline and niacinamide.
AB  - BACKGROUND: Generalized discoid lupus erythematosus (DLE) is an autoimmune skin
      disease variant rarely reported in dogs. The antimalarial immunomodulator
      hydroxychloroquine has been suggested as maintenance therapy for generalized DLE
      in one dog, but several recurrences were noted in the 1 year follow-up of that
      patient. HYPOTHESIS/OBJECTIVE: To describe the effective treatment of generalized
      DLE with ciclosporin in one dog. ANIMAL: A 6-year-old, castrated male crossbred
      dog was presented with pruritic, well-demarcated annular to polycyclic,
      hyperpigmented plaques with marginal erythema on the dorsal head, neck, trunk and
      medial extremities; these had been nonresponsive to treatment with doxycycline
      and niacinamide. METHODS: Investigation included complete blood count, serum
      chemistry profile, urinalysis, serum antinuclear antibody test, histopathological
      examination and direct immunofluorescence testing of skin biopsies. RESULTS: The
      presence of lymphocyte-rich interface dermatitis on histology, together with
      generalized chronic recurrent hyperpigmented plaques, was consistent with the
      diagnosis of a generalized variant of DLE. The absence of systemic signs and
      unremarkable laboratory tests excluded concurrent systemic lupus erythematosus.
      Treatment was initiated with oral dexamethasone and ciclosporin. After 1 month,
      dexamethasone was discontinued and oral ketoconazole was added to the therapeutic
      regimen. Four months later, pruritus and erythema resolved, with most skin
      lesions becoming impalpable. Over the last 6 months, the patient's DLE was
      maintained in remission with oral ciclosporin and ketoconazole in combination
      every 3 days. CONCLUSIONS AND CLINICAL IMPORTANCE: The combination of ciclosporin
      and ketoconazole appeared effective to induce and maintain lesion remission in
      this dog with generalized DLE.

PMID- 24916385
TI  - MetAssign: probabilistic annotation of metabolites from LC-MS data using a
      Bayesian clustering approach.
AB  - MOTIVATION: The use of liquid chromatography coupled to mass spectrometry has
      enabled the high-throughput profiling of the metabolite composition of biological
      samples. However, the large amount of data obtained can be difficult to analyse
      and often requires computational processing to understand which metabolites are
      present in a sample. This article looks at the dual problem of annotating peaks
      in a sample with a metabolite, together with putatively annotating whether a
      metabolite is present in the sample. The starting point of the approach is a
      Bayesian clustering of peaks into groups, each corresponding to putative adducts
      and isotopes of a single metabolite. RESULTS: The Bayesian modelling introduced
      here combines information from the mass-to-charge ratio, retention time and
      intensity of each peak, together with a model of the inter-peak dependency
      structure, to increase the accuracy of peak annotation. The results inherently
      contain a quantitative estimate of confidence in the peak annotations and allow
      an accurate trade-off between precision and recall. Extensive validation
      experiments using authentic chemical standards show that this system is able to
      produce more accurate putative identifications than other state-of-the-art
      systems, while at the same time giving a probabilistic measure of confidence in
      the annotations. AVAILABILITY AND IMPLEMENTATION: The software has been
      implemented as part of the mzMatch metabolomics analysis pipeline, which is
      available for download at http://mzmatch.sourceforge.net/.

PMID- 24916386
TI  - An ELISA kit with two detection modes for the diagnosis of lymphatic filariasis.
AB  - The aim of this study was to develop a low-cost antifilarial immunoglobulin (Ig)
      G4 detection kit for the diagnosis of lymphatic filariasis. The kit was designed
      to be used by minimally trained personnel without the constraints of expensive
      laboratory equipment. We provide a description of the development and validation
      of a single-serum-dilution based enzyme-linked immunosorbent assay (ELISA) kit
      with ready-to-use reagents for measuring antifilarial IgG4 antibodies. The kit
      was tested on residents in Brugia malayi-endemic areas in southern Thailand.
      Detection was performed by naked-eye observation of the resultant colour of the
      immunological reactivity. The coefficient of variation (CV) was used to assess
      the reproducibility of the results. Long-term stability was measured over a 6
      month period. Sensitivity of the test kit was 97% when compared with
      microfilariae detection in thick blood smears. Specificity was 98.7% based on the
      sera of 57 patients living outside the endemic areas who were infected with other
      parasites and 100 parasite-free subjects. All positive CVs were < 10%. The test
      kit was remarkably stable over 6 months. Field validation was performed by the
      detection of antifilarial IgG4 in 4365 serum samples collected from residents of
      brugian filariasis-endemic areas and compared with outcome colours of the test
      samples by the naked eye. Subsequent ELISA evaluation of these results using an
      ELISA reader indicated high agreement by the kappa statistic. These results
      demonstrate that the test kit is efficient and useful for public health
      laboratories as an alternative tool for the diagnosis of lymphatic filarial
      infection.

PMID- 24916387
TI  - C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47.
AB  - Cytidine (C) to Uridine (U) RNA editing is a post-transcriptional modification
      that is accomplished by the deaminase APOBEC1 and its partnership with the RNA
      binding protein A1CF. We identify and characterise here a novel RNA-binding
      protein, RBM47, that interacts with APOBEC1 and A1CF and is expressed in tissues
      where C to U RNA editing occurs. RBM47 can substitute for A1CF and is necessary
      and sufficient for APOBEC1-mediated editing in vitro. Editing is further impaired
      in Rbm47-deficient mutant mice. These findings suggest that RBM47 and APOBEC1
      constitute the basic machinery for C to U RNA editing. 

PMID- 24916388
TI  - Structural basis for polyspecificity in the POT family of proton-coupled
      oligopeptide transporters.
AB  - An enigma in the field of peptide transport is the structural basis for ligand
      promiscuity, as exemplified by PepT1, the mammalian plasma membrane peptide
      transporter. Here, we present crystal structures of di- and tripeptide-bound
      complexes of a bacterial homologue of PepT1, which reveal at least two mechanisms
      for peptide recognition that operate within a single, centrally located binding
      site. The dipeptide was orientated laterally in the binding site, whereas the
      tripeptide revealed an alternative vertical binding mode. The co-crystal
      structures combined with functional studies reveal that biochemically distinct
      peptide-binding sites likely operate within the POT/PTR family of proton-coupled
      symporters and suggest that transport promiscuity has arisen in part through the
      ability of the binding site to accommodate peptides in multiple orientations for
      transport. 

PMID- 24916389
TI  - Effects of TWIN-OF-EYELESS on Clock Gene Expression and Central-Pacemaker Neuron
      Development in Drosophila.
AB  - Circadian oscillators are autonomous molecular rhythms that reside in cells to
      align whole-organism physiology and behavior to the 24-h day. In flies, as in
      mammals, the oscillator operates in cells that coexpress CLOCK (CLK) and CYCLE
      (CYC). Recent work in Drosophila has shown that CLK is unique in its ability to
      generate heterologous oscillators, indicating that Clk gene expression defines
      the circadian cell fate. Here, using standard in vitro and in vivo techniques, we
      show that TWIN-OF-EYELESS (TOY; dPax6) regulates Clk expression in small
      ventrolateral neurons (s-LNvs) that coordinate sleep-wake cycles. Crucially, toy
      binds multiple sites at the Clk locus, is expressed independent of CLK-CYC in
      LNvs, regulates CLK protein levels under optimal photoperiodic conditions, and
      sets clock-speed during endogenous free-run. Furthermore, TOY is necessary for
      the onset of Clk expression in LNvs during embryogenesis. We propose that TOY
      contributes to a transcription complex that functions upstream of the oscillator
      to promote Clk expression in s-LNvs.

PMID- 24916390
TI  - Natural Populations of Drosophila melanogaster Reveal Features of an
      Uncharacterized Circadian Property: The Lower Temperature Limit of Rhythmicity.
AB  - Most cyclic biological processes are under control of a circadian molecular
      timing system that synchronizes these phenomena to the 24-h day. One generic
      property of circadian-controlled processes is that they operate within a specific
      temperature range, below which the manifestation of rhythm ceases. Little is
      known about the evolutionary relevance of the lower temperature limit of
      rhythmicity or about the mechanism underlying the loss of overt circadian
      behavior below this lower limit, especially in one model organism of
      chronobiology, Drosophila melanogaster. Natural populations of Drosophila are
      evolving under divergent selection pressures and so provide a source of diversity
      necessary to address these issues. Using lines derived from African populations,
      we find that there is natural variation in the expression of rhythmic behavior
      under low-temperature conditions. We found evidence that this variability is
      evolutionarily relevant at extremely low temperature (12  degrees C) because high
      altitude populations exhibit selection for locally adapted genomes that
      contribute to rhythmic behavior. Lines resistant to 15  degrees C show an
      additional layer of diversity in their response to temperature extremes because
      some lines are resistant to low temperature (15  degrees C) only, whereas others
      are cross-resistant to high and low temperature (15  degrees C and 30  degrees
      C). Genetic analysis of one cold-resistant circadian line at 15  degrees C
      reveals that the phenotype maps to the X-chromosome but not to the core clock
      genes, per and sgg. Analysis of the central clock cells of this line reveals that
      maintenance of rhythm is associated with robust clock function, which is
      compromised in a standard laboratory strain. These data indicate that the cold
      resistant circadian phenotype is clock based. This study highlights the
      importance of using natural populations to inform us of the basic features of
      circadian traits, especially those that might be under temperature-based
      selection.

PMID- 24916392
TI  - Behavioral Masking and cFos Responses to Light in Day- and Night-Active Grass
      Rats.
AB  - Light not only entrains the circadian system but also has acute effects on
      physiology and behavior, a phenomenon known as masking. Behavioral masking
      responses to bright light differ in diurnal and nocturnal species, such that
      light increases arousal in the former and decreases it in the latter. Comparisons
      made within a species that displays both diurnal and nocturnal patterns of
      behavior may provide insight into how masking differs between chronotypes and the
      association between mechanisms controlling masking and the circadian drive for
      activity. Nile grass rats (Arvicanthis niloticus) provide a useful model for
      studying such issues because when these animals are housed with running wheels,
      some run primarily during day, while others run at night. Here we compared
      behavioral masking responses to 2-h pulses of light and darkness given across a
      12:12 light/dark cycle in day-active (DA) and night-active (NA) grass rats. Both
      wheel-running activity (WRA) and general activity (GA) were monitored. Light
      pulses at night tended to increase both WRA and GA overall in the DA grass rats,
      while in NA grass rats, light pulses significantly reduced WRA but had no effect
      on GA. Dark pulses during the day tended to decrease both WRA and GA in the DA
      grass rats, while in the NA grass rats, they tended to increase WRA in the early
      day but had no effect on GA overall. Next, we measured cFos expression within 2
      brain areas potentially involved in masking, the intergeniculate leaflet (IGL)
      and the olivary pretectal area (OPT), of DA and NA grass rats either sacrificed
      on a control night or after a 1-h light pulse at ZT14. In DA grass rats, light at
      ZT14 induced cFos in the IGL and OPT, whereas in NA grass rats, cFos levels in
      both structures were high at ZT14 and were not altered by a 1-h light pulse.
      Overall, these results suggest that masking responses to light and darkness are
      dependent on the chronotype of the individual and that the responsiveness of the
      IGL and OPT to light may depend on or contribute to the behavioral response of
      these animals.

PMID- 24916393
TI  - Social and Environmental Influences on Daily Activity Pattern in Free-Living
      Subterranean Rodents: The Case of a Eusocial Bathyergid.
AB  - Predictable daily activity patterns have been detected repeatedly even in mammals
      living in stable environments, as is the case for subterranean rodents. Whereas
      studies on activity of these rodents under laboratory conditions almost
      exclusively have concerned themselves with the influence of light, many field
      studies have revealed signs of an association between the activity pattern and
      daily fluctuations of temperature under the ground. This would assume that
      behavioral thermoregulation is probably involved. The only exceptions to the
      relationship between temperature and activity are 2 eusocial mole-rats of the
      genus Fukomys (Bathyergidae, Rodentia), which indicates that activity patterns
      could be affected also by social cues. To better understand how social and
      environmental factors influence the activity pattern in a eusocial mole-rat, we
      monitored the outside-nest activity in another species of this genus, the
      Ansell's mole-rat (Fukomys anselli), which has a relatively small body mass, high
      conductance, and more superficially situated burrows. Its daily activity had 1
      prominent peak (around 1400 h), and it was tightly correlated with the
      temperature measured at depth of foraging burrows. Since F. anselli has high
      thermoregulatory requirements to maintain stable body temperature below the lower
      critical temperature, we conclude that the observed pattern is probably the
      result of minimizing the cost of thermoregulation. There were no significant
      differences in the daily activity patterns of breeding males and females and
      nonbreeders. Members of the same family group tended to have more similar
      activity patterns, but consistent activity synchronization between individuals
      was not proven. From the comparison of available data on all subterranean
      rodents, we assume that social cues in communally nesting mole-rats may disrupt
      (mask) temperature-related daily activity rhythms but probably only if the
      additional cost of thermoregulation is not too high, as it likely is in the
      Ansell's mole-rat.

PMID- 24916391
TI  - Effects of Pinealectomy and Short Day Lengths on Reproduction and Neuronal RFRP
      3, Kisspeptin, and GnRH in Female Turkish Hamsters.
AB  - Long days (LDs) stimulate and short days (SDs) inhibit reproduction in
      photoperiodic rodents by modifying nocturnal pineal melatonin secretion. In LD
      Turkish hamsters, unlike other rodents, pinealectomy induces reproductive
      quiescence comparable to that produced by SDs. We assessed whether SDs and
      pinealectomy induce similar or different patterns of kisspeptin and gonadotropin
      inhibitory hormone (also known as RFamide-related peptide-3 [RFRP-3] in mammals)
      expression, important mediators of seasonal reproductive changes in other
      species. Brains were harvested from sham-operated female Turkish hamsters
      maintained in LDs and SDs and LD-pinealectomized (pinx) females, all housed in
      their respective photoperiods for 12 weeks. Uterine weights were substantially
      higher in LD-sham than in LD-pinx and SD-sham females. RFRP-3-immunoreactive(-ir)
      cells in the dorsomedial hypothalamic nucleus were greater in number and size in
      the reproductively competent LD-sham hamsters than in both reproductively
      suppressed SD-sham and LD-pinx hamsters. LD-sham hamsters had more kisspeptin-ir
      cells in the anteroventral periventricular nucleus than did LD-pinx hamsters.
      Reproductive quiescence, whether induced by short-day lengths or pinealectomy,
      was generally accompanied by comparable changes in RFRP-3 and kisspeptin,
      suggesting that long-duration melatonin signaling and withdrawal of melatonin by
      pinealectomy may act through the same neural substrates to induce gonadal
      quiescence.

PMID- 24916394
TI  - Circadian Rhythm Disorders and Melatonin Production in 127 Blind Women with and
      without Light Perception.
AB  - Light is the major environmental time cue that synchronizes the endogenous
      central circadian pacemaker, located in the suprachiasmatic nuclei of the
      hypothalamus, and is detected exclusively by the eyes primarily via specialized
      non-rod, non-cone ganglion cell photoreceptors. Consequently, most blind people
      with no perception of light (NPL) have either nonentrained or abnormally phased
      circadian rhythms due to this inability to detect light. Conversely, most
      visually impaired participants with some degree of light perception (LP) exhibit
      normal entrainment, emphasizing the functional separation of visual and
      "nonvisual" photoreception. The aims of the study were to identify the prevalence
      of circadian disorders in blind women, with the further aim of examining how eye
      disease may relate to the type of circadian disorder. Participants (n = 127, age
      50.8 +/- 13.4 years) completed an 8-week field study including daily sleep
      diaries and sequential 4 to 8 hourly urine collections over 48 h on 2 to 3
      occasions separated by at least 2 weeks. Circadian type was determined from the
      timing and time course of the melatonin rhythm measured by cosinor-derived
      urinary 6-sulfatoxymelatonin rhythm peak. Of the participants with NPL (n = 41),
      the majority were abnormally phased (24%) or nonentrained (39%), with 37%
      classified as normally entrained. Of the participants with LP (n = 86), the
      majority were normally entrained (69%). Eighteen LP participants (21%) were
      abnormally phased (8 advanced, 10 delayed). Nine LP participants (10%) were
      nonentrained. The eye conditions most associated with abnormal phase and/or
      nonentrained circadian rhythms were bilateral enucleation (67%) and retinopathy
      of prematurity (57%). By contrast, 84% of participants with retinitis pigmentosa
      and 83% of those with age-related macular degeneration were normally entrained.
      These findings suggest that the etiology of blindness in addition to LP status is
      related to an individual's ability to process the circadian light signal.

PMID- 24916395
TI  - Incorrect Equations.
AB  - Woller A and Gonze D (2013) The bird circadian clock: insights from a
      computational model. J Biol Rhythms 28(6):390-402. (Original DOI:
      10.1177/0748730413512454).

PMID- 24916396
TI  - Magnetic resonance imaging of the effortful swallow.
AB  - OBJECTIVE: The effortful swallow was designed to improve posterior mobility of
      the tongue base and increase intraoral pressures. We characterized the effects of
      this maneuver via dynamic magnetic resonance imaging (dMRI) in healthy patients.
      METHODS: A 3-T scanner was used to obtain dMRI images of patients swallowing
      pudding using normal as well as effortful swallows. Ninety sequential images were
      acquired at the level of the oropharynx in the axial plane for each swallow; 3
      series were obtained for each swallow type for each patient. Images were acquired
      every 113 ms during swallowing. The images were analyzed with respect to
      oropharyngeal closure duration, anteroposterior and transverse distance between
      the oropharyngeal walls, and oropharyngeal area before and after closure.
      RESULTS: Preswallow reduced pharyngeal area was observed (P = .02; mean = 212.61
      mm2 for effortful, mean = 261.92 mm2 for normal) as well as prolonged pharyngeal
      closure during the swallow (P < .0001; mean = 742.18 ms for effortful, mean =
      437.31 ms for normal). No other differences were noted between swallow types.
      Interrater and intrarater reliability of all measurements was excellent.
      CONCLUSION: This preliminary investigation is the first to evaluate the effects
      of effortful swallows via dMRI. In our cohort, consistent physiologic changes
      were elicited, consistent with clinical dogma regarding this maneuver.

PMID- 24916397
TI  - Method to estimate the deviation from ideal uniaxial compression during freehand
      elastography.
AB  - Quasi-static ultrasound elastography was introduced in the early 1990s to provide
      a way to visualize the mechanical properties of target tissue. Most commonly,
      only the axial strain is imaged and referred to as an Axial Strain Elastogram
      (ASE) or elastogram for simplicity. It has been shown that one can image the
      axial-shear strain distributions as well in addition to ASE. The image of the
      axial-shear strain is referred to as an axial-shear strain elastogram (ASSE). It
      has also been shown that the presence or absence of non-zero axial-shear strain
      values inside the inclusion (referred to as fill-in) along with contrasting
      margin at its boundary may serve as a potential feature from ASSE that can aid in
      non-invasive breast lesion classification. However, during freehand elastography,
      deviations from uniaxial compression often occur typically appearing in several
      of the frames of a cine-loop obtained during compression. It was shown recently
      that accounting for such deviations would be important for reliable
      interpretation of the "fill-in" observed in ASSE. In this article, we describe a
      method to estimate the angle of iso-displacement contour at a given depth and use
      this as a measure to quantify the deviation from the desired uniaxial compression
      during freehand elastography. We validate the estimated angle obtained from the
      axial-displacement map against the designed values in simulation and tissue
      mimicking phantom experiments. The potential of the angle estimate to detect
      unreliable ASSE frames among the freehand-acquired data cine-loop is demonstrated
      using example cases of in vivo breast lesion data. Based on the results, we
      conclude that the angle of the iso-displacement contour from the axial
      displacement map can be used as a metric to qualify an ASSE frame as reliable to
      interpret or not. Importantly, this metric can be obtained in real time and thus
      can provide operator feedback to guide and improve in vivo freehand elastography
      data acquisition quality. 

PMID- 24916398
TI  - Snail and Slug mediate tamoxifen resistance in breast cancer cells through
      activation of EGFR-ERK independent of epithelial-mesenchymal transition.

PMID- 24916399
TI  - Back to basic physiological questions and consideration of fluids as drugs.

PMID- 24916400
TI  - Heterogeneity of epidemiological factors by breast tumor subtypes in Korean
      women: a case-case study.
AB  - Breast cancer is heterogeneous in clinical behavior by subtypes; however, it is
      unclear how this heterogeneity is related to epidemiological factors. To evaluate
      the differences in epidemiological factors by breast tumor subtypes, we
      investigated the associations of epidemiological factors between tumor subtypes
      in Korean women. From the Seoul Breast Cancer Study, a total of 3,058 patients
      with breast cancer were included in the analyses. Tumor subtypes were classified
      based on hormone receptor (HR) and human epidermal growth factor receptor 2
      (HER2) statuses. The epidemiological factors of each subtype were compared
      through case-case analyses using multivariate a polytomous logistic regression
      model adjusted for age and recruiting centers. The distribution of the subtypes
      was as follows: 1,714 HR+ HER2- (56.0%), 414 HR+ HER2+ (13.5%), 423 HR- HER2+
      (13.9%) and 507 HR- HER2- (16.6%) patients with breast cancer. There were
      significant differences in age, menopausal status, age at menarche, number of
      children, age at first full-term pregnancy (FFTP), duration of breastfeeding and
      duration of endogenous estrogen exposure between tumor subtypes (p < 0.05).
      Compared to HR+ HER2- patients, the other subtype patients showed more frequency
      in having more numbers of children and less frequency in having earlier menarche,
      later FFTP and longer endogenous estrogen exposure. Although HR- HER2+ patients
      were less obese, HR- HER2- patients were younger and more obese. In conclusion,
      age, body mass index and reproductive factors were differentially associated with
      breast tumor subtypes suggesting a possible distinct etiology for tumor
      progression. 

PMID- 24916401
TI  - Asymmetric synthesis of isoindolones by chiral cyclopentadienyl-rhodium(III)
      catalyzed C-H functionalizations.
AB  - Directed Cp*Rh(III)-catalyzed carbon-hydrogen (C-H) bond functionalizations have
      evolved as a powerful strategy for the construction of heterocycles. Despite
      their high value, the development of related asymmetric reactions is largely
      lagging behind due to a limited availability of robust and tunable chiral
      cyclopentadienyl ligands. Rhodium complexes comprising a chiral Cp ligand with an
      atropchiral biaryl backbone enables an asymmetric synthesis of isoindolones from
      arylhydroxamates and weakly alkyl donor/acceptor diazo derivatives as one-carbon
      component under mild conditions. The complex guides the substrates with a high
      double facial selectivity yielding the chiral isoindolones in good yields and
      excellent enantioselectivities.

PMID- 24916402
TI  - Factors influencing unspecified chest pain admission rates in England.
AB  - BACKGROUND: Unspecified chest pain is an important and potentially avoidable
      cause of emergency hospital admission. We aimed to examine inter-hospital
      variation in admission rates with unspecified chest pain and identify population
      characteristics, services and technologies that might explain this variation.
      METHODS: We used Hospital Episodes Statistics data from 152 acute trusts in
      England to calculate a direct standardised annual admission rate per 100,000
      population for each trust. Regression analysis was used to identify factors
      explaining variation, first, using routinely available data relating to the
      hospital catchment area and service and then using responses to a survey of
      emergency department (ED) management. RESULTS: The best predictors of admission
      rate using routine data were total beds per 1000 population (p=0.001), rapid
      access chest pain clinic (RACPC) attendances per year (p<0.001) and percentage of
      households in poverty (p=0.01). Including data from 105/142 (74%) survey
      responses, the best predictors of admission rate were total beds (p<0.001), RACPC
      attendances (p=0.001), mean ED waiting time (p=0.049) and percentage of
      households in poverty (p<0.001). All associations were positive (higher variable
      predicts higher rate) except ED waiting time. We found no significant
      associations between factors relating to acute chest pain management and
      admission rate. CONCLUSIONS: Hospitals with higher admission rates for
      unspecified chest pain have greater bed provision, more RACPC attendances and
      serve populations with a higher percentage of households in poverty. These
      findings may be explained by services responding to demand in populations with
      greater need. We found no evidence that chest pain management influenced
      admission rates.

PMID- 24916404
TI  - Human macrophage polarization in vitro: maturation and activation methods
      compared.
AB  - Macrophages form a heterogeneous cell population displaying multiple functions,
      and can be polarized into pro- (M1) or anti-inflammatory (M2) macrophages, by
      environmental factors. Their activation status reflects a beneficial or
      detrimental role in various diseases. Currently several in vitro maturation and
      activation protocols are used to induce an M1 or M2 phenotype. Here, the impact
      of different maturation factors (NHS, M-CSF, or GM-CSF) and activation methods
      (IFN-gamma/LPS, IL-4, dexamethason, IL-10) on the macrophage phenotype was
      determined. Regarding macrophage morphology, pro-inflammatory (M1) activation
      stimulated cell elongation, and anti-inflammatory (M2) activation induced a
      circular appearance. Activation with pro-inflammatory mediators led to increased
      CD40 and CD64 expression, whereas activation with anti-inflammatory factors
      resulted in increased levels of MR and CD163. Production of pro-inflammatory
      cytokines was induced by activation with IFN-gamma/LPS, and TGF-beta production
      was enhanced by the maturation factors M-CSF and GM-CSF. Our data demonstrate
      that macrophage marker expression and cytokine production in vitro is highly
      dependent on both maturation and activation methods. In vivo macrophage
      activation is far more complex, since a plethora of stimuli are present. Hence,
      defining the macrophage activation status ex vivo on a limited number of markers
      could be indecisive. From this study we conclude that maturation with M-CSF or GM
      CSF induces a moderate anti- or pro-inflammatory state respectively, compared to
      maturation with NHS. CD40 and CD64 are the most distinctive makers for human M1
      and CD163 and MR for M2 macrophage activation and therefore can be helpful in
      determining the activation status of human macrophages ex vivo.

PMID- 24916405
TI  - The N-terminal fragment of the beta-amyloid precursor protein of Alzheimer's
      disease (N-APP) binds to phosphoinositide-rich domains on the surface of
      hippocampal neurons.
AB  - The function of the beta-amyloid precursor protein (APP) of Alzheimer's disease
      is poorly understood. The secreted ectodomain fragment of APP (sAPPalpha) can be
      readily cleaved to produce a small N-terminal fragment (N-APP) that contains
      heparin-binding and metal-binding domains and that has been found to have
      biological activity. In the present study, we examined whether N-APP can bind to
      lipids. We found that N-APP binds selectively to phosphoinositides (PIPs) but
      poorly to most other lipids. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 )
      rich microdomains were identified on the extracellular surface of neurons and
      glia in primary hippocampal cultures. N-APP bound to neurons and colocalized with
      PIPs on the cell surface. Furthermore, the binding of N-APP to neurons increased
      the level of cell-surface PI(4,5)P2 and phosphatidylinositol 3,4,5-trisphosphate.
      However, PIPs were not the principal cell-surface binding site for N-APP, because
      N-APP binding to neurons was not inhibited by a short-acyl-chain PIP analogue,
      and N-APP did not bind to glial cells which also possessed PI(4,5)P2 on the cell
      surface. The data are explained by a model in which N-APP binds to two distinct
      components on neurons, one of which is an unidentified receptor and the second of
      which is a PIP lipid, which binds more weakly to a distinct site within N-APP.
      Our data provide further support for the idea that N-APP may be an important
      mediator of APP's biological activity.

PMID- 24916407
TI  - The impact and importance of clinical learning experience in supporting nursing
      students in end-of-life care: cluster analysis.
AB  - BACKGROUND: Nursing students are often expected to provide end-of-life care to
      patients during clinical practice. Little research has been conducted to examine
      the heterogeneity of the students and how learning outcomes are affected by their
      education experience and other demographic factors. AIM: The aim of this study
      was to identify and compare groups of nursing students based on their
      demographics, clinical experience, knowledge, perceived competency, and attitude
      towards end-of-life care. METHOD: A group of 253 nursing students was asked to
      complete a cross-sectional survey to explore their clinical experience,
      knowledge, attitude, and perceived competency towards end-of-life care. Cluster
      analysis was used to determine whether specific groups of students could be
      identified within the study cohort. RESULTS: Three distinct clusters were
      identified. Students from the three clusters showed no significant differences in
      end-of-life knowledge. Significant differences were identified in clinical
      experience amongst the three clusters and in attitude and perceived competency
      within the clusters. The cluster of students that had greater clinical experience
      demonstrated higher perceived competency and a more positive attitude towards end
      of-life care. CONCLUSION: Clinical experience was found to be crucial in
      enhancing the perceived competency and attitude of nursing students in end-of
      life care.

PMID- 24916406
TI  - SH3BP2 cherubism mutation potentiates TNF-alpha-induced osteoclastogenesis via
      NFATc1 and TNF-alpha-mediated inflammatory bone loss.
AB  - Cherubism (OMIM# 118400) is a genetic disorder with excessive jawbone resorption
      caused by mutations in SH3 domain binding protein 2 (SH3BP2), a signaling adaptor
      protein. Studies on the mouse model for cherubism carrying a P416R knock-in (KI)
      mutation have revealed that mutant SH3BP2 enhances tumor necrosis factor (TNF)
      alpha production and receptor activator of nuclear factor-kappaB ligand (RANKL)
      induced osteoclast differentiation in myeloid cells. TNF-alpha is expressed in
      human cherubism lesions, which contain a large number of tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells, and TNF-alpha plays a critical
      role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2(KI/KI)
      ). The data suggest a pathophysiological relationship between mutant SH3BP2 and
      TNF-alpha-mediated bone loss by osteoclasts. Therefore, we investigated whether
      P416R mutant SH3BP2 is involved in TNF-alpha-mediated osteoclast formation and
      bone loss. Here, we show that bone marrow-derived M-CSF-dependent macrophages
      (BMMs) from the heterozygous cherubism mutant (Sh3bp2(KI/+) ) mice are highly
      responsive to TNF-alpha and can differentiate into osteoclasts independently of
      RANKL in vitro by a mechanism that involves spleen tyrosine kinase (SYK) and
      phospholipase Cgamma2 (PLCgamma2) phosphorylation, leading to increased nuclear
      translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone
      loss with increased osteoclast formation in a mouse calvarial TNF-alpha injection
      model as well as in a human TNF-alpha transgenic mouse model (hTNFtg). SH3BP2
      knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated
      cell formation. These findings suggest that the SH3BP2 cherubism mutation can
      cause jawbone destruction by promoting osteoclast formation in response to TNF
      alpha expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF
      alpha-induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast
      progenitors could be a potential strategy for the treatment of bone loss in
      cherubism as well as in other inflammatory bone disorders.

PMID- 24916408
TI  - Characterization of the diversity in bat biosonar beampatterns with spherical
      harmonics power spectra.
AB  - The biosonar beampatterns found across different bat species are highly diverse
      in terms of global and local shape properties such as overall beamwidth or the
      presence, location, and shape of multiple lobes. It may be hypothesized that some
      of this variability reflects evolutionary adaptation. To investigate this
      hypothesis, the present work has searched for patterns in the variability across
      a set of 283 numerical predictions of emission and reception beampatterns from 88
      bat species belonging to four major families (Rhinolophidae, Hipposideridae,
      Phyllostomidae, Vespertilionidae). This was done using a lossy compression of the
      beampatterns that utilized real spherical harmonics as basis functions. The
      resulting vector representations showed differences between the families as well
      as between emission and reception. These differences existed in the means of the
      power spectra as well as in their distribution. The distributions were
      characterized in a low dimensional space found through principal component
      analysis. The distinctiveness of the beampatterns across the groups was
      corroborated by pairwise classification experiments that yielded correct
      classification rates between ~85 and ~98%. Beamwidth was a major factor but not
      the sole distinguishing feature in these classification experiments. These
      differences could be seen as an indication of adaptive trends at the beampattern
      level.

PMID- 24916409
TI  - Structure factor model for understanding the measured backscatter coefficients
      from concentrated cell pellet biophantoms.
AB  - Ultrasonic backscatter coefficient (BSC) measurements were performed on K562 cell
      pellet biophantoms with cell concentrations ranging from 0.006 to 0.30 in the 10
      42 MHz frequency bandwidth. Three scattering models, namely, the fluid-filled
      sphere model (FFSM), the particle model (PM), and the structure factor model
      (SFM), were compared for modeling the scattering from an ensemble of concentrated
      cells. A parameter estimation procedure was developed in order to estimate the
      scatterer size and relative impedance contrast that could explain the measured
      BSCs from all the studied cell concentrations. This procedure was applied to the
      BSC data from K562 cell pellet biophantoms in the 10-42 MHz frequency bandwidth
      and to the BSC data from Chinese hamster ovary cell pellet biophantoms in the 26
      105 MHz frequency bandwidth given in Han, Abuhabsah, Blue, Sarwate, and O'Brien
      [J. Acoust. Soc. Am. 130, 4139-4147 (2011)]. The data fitting quality and the
      scatterer size estimates show that the SFM was more suitable than the PM and the
      FFSM for modeling the responses from concentrated cell pellet biophantoms.

PMID- 24916410
TI  - Flow rate and duty cycle effects in lysis of Chlamydomonas reinhardtii using high
      energy pulsed focused ultrasound.
AB  - To consider microalgae lipid biofuel as a viable energy source, it is a necessity
      to maximize algal cell lysis, lipid harvest, and thus biofuel production versus
      the energy used to lyse the cells. Previous techniques have been to use energy
      consumptive ultrasound waves in the 10-40 kHz range in a stationary exposure
      environment. This study evaluated the potential of using 1.1 MHz ultrasound
      pulses in a new flow through type chamber on Chlamydomonas reinhardtii as a model
      organism for cell breakage. The ultrasound was generated using a spherically
      focused transducer with a focal length of 6.34 cm and an active diameter of 6.36
      cm driven by 20 cycle sine-wave tone bursts at varied pulse repetition
      frequencies. First, variations in flow rate were examined at a constant duty
      cycle of 3.6%. After assessing flow rates, the duty cycle was varied to further
      explore the dependence on the tone burst parameters. Cell lysis was assessed by
      quantifying protein and chlorophyll release into the supernatant as well as by
      lipid extractability. Appropriate flow rates with higher duty cycles led to
      statistically significant increases in cell lysis relative to controls and other
      exposure conditions. 

PMID- 24916411
TI  - Phylogenetic tree shapes resolve disease transmission patterns.
AB  - BACKGROUND AND OBJECTIVES: Whole-genome sequencing is becoming popular as a tool
      for understanding outbreaks of communicable diseases, with phylogenetic trees
      being used to identify individual transmission events or to characterize outbreak
      level overall transmission dynamics. Existing methods to infer transmission
      dynamics from sequence data rely on well-characterized infectious periods,
      epidemiological and clinical metadata which may not always be available, and
      typically require computationally intensive analysis focusing on the branch
      lengths in phylogenetic trees. We sought to determine whether the topological
      structures of phylogenetic trees contain signatures of the transmission patterns
      underlying an outbreak. METHODOLOGY: We use simulated outbreaks to train and then
      test computational classifiers. We test the method on data from two real-world
      outbreaks. RESULTS: We show that different transmission patterns result in
      quantitatively different phylogenetic tree shapes. We describe topological
      features that summarize a phylogeny's structure and find that computational
      classifiers based on these are capable of predicting an outbreak's transmission
      dynamics. The method is robust to variations in the transmission parameters and
      network types, and recapitulates known epidemiology of previously characterized
      real-world outbreaks. CONCLUSIONS AND IMPLICATIONS: There are simple structural
      properties of phylogenetic trees which, when combined, can distinguish
      communicable disease outbreaks with a super-spreader, homogeneous transmission
      and chains of transmission. This is possible using genome data alone, and can be
      done during an outbreak. We discuss the implications for management of outbreaks.

PMID- 24916412
TI  - Insights into PARP Inhibitors' Selectivity Using Fluorescence Polarization and
      Surface Plasmon Resonance Binding Assays.
AB  - PARP inhibitors are an exciting new class of antineoplastic drugs that have been
      proven to be efficacious as single agents in cancer settings with inherent DNA
      repair defects, as well as in combination with DNA-damaging chemotherapeutics.
      Currently, they are designed to target the catalytic domain of PARP-1, the most
      studied member of the family, with a key role in the DNA-damage repair process.
      Because PARP inhibitors are substrate (NAD(+)) competitors, there is a need for a
      deeper understanding of their cross-reactivity. This is particularly relevant for
      PARP-2, the PARP-1 closest homologue, for which an embryonic lethal phenotype has
      been observed in double knockout mice. In this study, we describe the development
      and validation of binding assays based on fluorescence polarization (FP) and
      surface plasmon resonance (SPR) techniques. PARP-1, PARP-2, PARP-3, and TNKS-1 FP
      displacement assays are set up by employing ad hoc synthesized probes. These
      assays are suitable for high-throughput screening (HTS) and selectivity
      profiling, thus allowing the identification of NAD(+)binding site selective
      inhibitors. The PARP-1 and PARP-2 complementary SPR binding assays confirm
      displacement data and the in-depth inhibitor characterization. Moreover, these
      formats have the potential to be broadly applicable to other members of the PARP
      family. 

PMID- 24916413
TI  - Effects of a ferulate-derived dihydrobenzofuran neolignan on angiogenesis,
      steroidogenesis, and redox status in a swine cell model.
AB  - In the ongoing search for new therapeutic compounds, lignans and neolignans,
      which are widely distributed in plants, deserve special attention because of
      their interactions with several biological targets. Searching for potential
      antiangiogenic agents related to natural lignans/neolignans, we were attracted by
      a previously studied synthetic dihydrobenzofuran neolignan. We synthesized the
      compound by means of an eco-friendly, enzyme-mediated biomimetic coupling of the
      methyl ester of ferulic acid, and the present study was aimed to deeply
      investigate its effect in angiogenesis bioassays validated in our laboratory. In
      addition, a previously well-defined granulosa cell model was employed to evaluate
      the effect of dihydrobenzofuran neolignan on cell viability, steroidogenesis, and
      redox status. Present data support the antiangiogenic effect of this neolignan.
      Moreover, we demonstrate that, at least at the highest concentrations tested,
      dihydrobenzofuran neolignan affects granulosa cell viability and steroidogenesis.
      In addition, the compound inhibits generation of free radicals and stimulates
      scavenger enzyme activities. The present data, which are a further deepening of
      the evaluation of the biological activities of the dihydrobenzofuran lignan in
      well-defined cell models, are of interest and worthy of special attention. 

PMID- 24916414
TI  - Direct access to the middle meningeal artery for embolization of complex dural
      arteriovenous fistula: a hybrid treatment approach.
AB  - Endovascular embolization has become increasingly favored over microsurgical
      resection for treatment of complex dural arteriovenous fistulas (DAVFs). However,
      endovascular treatment can be restricted by tortuous transarterial access and a
      transvenous approach is not always feasible. We present a Borden III DAVF treated
      by direct access to the middle meningeal artery (MMA) and Onyx embolization
      performed in a hybrid operating room-angiography suite. A middle-aged patient
      with pulsatile headaches was found to have left transverse sinus occlusion and
      DAVF with retrograde cortical venous drainage fed by multiple external carotid
      artery (ECA) feeders. Endovascular attempts via conventional transvenous and
      transarterial routes were unsuccessful, and the major MMA feeder was accessed
      directly after temporal craniotomy was performed under neuronavigation. Onyx
      embolization was performed; complete occlusion of the fistula was achieved. Three
      month follow-up angiography showed no residual filling; the patient remains
      complication-free. A combined surgical-endovascular technique in a hybrid
      operating room-angiography suite can be an effective treatment for DAVFs
      complicated by inaccessible arterial and transvenous approaches. 

PMID- 24916415
TI  - Impact of the ASPECT scores and distribution on outcome among patients undergoing
      thrombectomy for acute ischemic stroke.
AB  - INTRODUCTION: This study investigates whether the Alberta Stroke Program Early CT
      Score (ASPECTS) quantification is associated with outcome following mechanical
      thrombectomy. OBJECTIVE: To determine whether preintervention non-perfect ASPECT
      scores involving cortical or subcortical regions and the side of the non-perfect
      ASPECT score affects outcomes. METHODS: A retrospective review of a prospectively
      maintained database of patients with acute ischemic stroke involving the anterior
      circulation who underwent thrombectomy between May 2008 and August 2012 at a
      single tertiary care center. The device for mechanical thrombectomy used was the
      penumbra aspiration system (Penumbra Inc, Alameda, California, USA) and the
      Solitaire stent retriever (ev3, Irvine, California, USA). A 'blinded'
      neuroradiologist obtained ASPECTS quantification and noted each region
      demonstrating early changes. RESULTS: 149 patients (51.7% female, mean age 66.1+/
      15.1 years) were included with an average National Institutes of Health Stroke
      Scale of 16.2+/-6.7. Patients with non-perfect ASPECT scores on pretreatment
      imaging were more likely to have a hemorrhagic conversion (p=0.04) evident on
      post-procedure CT. However, functional outcomes were the same. Patients with both
      cortical and basal ganglia non-perfect ASPECT scores were more likely to be in a
      persistent vegetative state or expire. No differences were identified in outcome
      among patients with left- versus right-sided infarcts affecting the basal ganglia
      or cortical regions. CONCLUSIONS: These findings support a strategy of selecting
      candidacy for thrombectomy that does not exclude patients with non-perfect ASPECT
      scores involving either the basal ganglia or cortical regions. Outcomes were
      identical among patients with no non-perfect ASPECT scores and those with
      cortical or subcortical infarcts, despite a higher incidence of hemorrhagic
      conversion found among those with non-perfect ASPECT scores.

PMID- 24916417
TI  - Association between socioeconomic status, surgical treatment and mortality in
      patients with colorectal cancer.
AB  - BACKGROUND: High socioeconomic status is associated with better survival in
      colorectal cancer (CRC). This study investigated whether socioeconomic status is
      associated with differences in surgical treatment and mortality in patients with
      CRC. METHODS: Patients diagnosed with stage I-III CRC between 2005 and 2010 in
      the Eindhoven Cancer Registry area in the Netherlands were included.
      Socioeconomic status was determined at a neighbourhood level by combining the
      mean household income and the mean value of the housing. RESULTS: Some 4422
      patients with colonic cancer and 2314 with rectal cancer were included. Patients
      with colonic cancer and high socioeconomic status were operated on with
      laparotomy (70.7 versus 77.6 per cent; P = 0.017), had laparoscopy converted to
      laparotomy (15.7 versus 29.5 per cent; P = 0.008) and developed anastomotic
      leakage or abscess (9.6 versus 12.6 per cent; P = 0.049) less frequently than
      patients with low socioeconomic status. These differences remained significant
      after adjustment for patient and tumour characteristics. In rectal cancer,
      patients with high socioeconomic status were more likely to undergo resection
      (96.3 versus 93.7 per cent; P = 0.083), but this was not significant in
      multivariable analysis (odds ratio (OR) 1.44, 95 per cent confidence interval
      0.84 to 2.46). The difference in 30-day postoperative mortality in patients with
      colonic cancer and high and low socioeconomic status (3.6 versus 6.8 per cent; P
      < 0.001) was not significant after adjusting for age, co-morbidities, emergency
      surgery, and anastomotic leakage or abscess formation (OR 0.90, 0.51 to 1.57).
      CONCLUSION: Patients with CRC and high socioeconomic status have more favourable
      surgical treatment characteristics than patients with low socioeconomic status.
      The lower 30-day postoperative mortality found in patients with colonic cancer
      and high socioeconomic status is largely explained by patient and surgical
      factors.

PMID- 24916416
TI  - Arf1 and Arf6 promote ventral actin structures formed by acute activation of
      protein kinase C and Src.
AB  - Arf proteins regulate membrane traffic and organelle structure. Although Arf6 is
      known to initiate actin-based changes in cell surface architecture, Arf1 may also
      function at the plasma membrane. Here we show that acute activation of protein
      kinase C (PKC) induced by the phorbol ester PMA led to the formation of motile
      actin structures on the ventral surface of Beas-2b cells, a lung bronchial
      epithelial cell line. Ventral actin structures also formed in PMA-treated HeLa
      cells that had elevated levels of Arf activation. For both cell types, formation
      of the ventral actin structures was enhanced by expression of active forms of
      either Arf1 or Arf6 and by the expression of guanine nucleotide exchange factors
      that activate these Arfs. By contrast, formation of these structures was blocked
      by inhibitors of PKC and Src and required phosphatidylinositol 4, 5-bisphosphate,
      Rac, Arf6, and Arf1. Furthermore, expression of ASAP1, an Arf1 GTPase activating
      protein (GAP) was more effective at inhibiting the ventral actin structures than
      was ACAP1, an Arf6 GAP. This study adds to the expanding role for Arf1 in the
      periphery and identifies a requirement for Arf1, a "Golgi Arf," in the
      reorganization of the cortical actin cytoskeleton on ventral surfaces, against
      the substratum.

PMID- 24916418
TI  - Ultrathin septuple layered PbBi2Se4 nanosheets.
AB  - Layered lead bismuth selenide, PbBi2Se4, an intergrowth compound of PbSe
      (rocksalt) and Bi2Se3 (hexagonal), is a topological insulator in the bulk phase.
      We present a simple solution based synthesis of two dimensional (2D) few seven
      atomic (septuple) layered PbBi2Se4 nanosheets (4-7 nm thick) for the first time.
      The excellent electrical transport in ultrathin PbBi2Se4 is attributed to the
      presence of dominant surface states that offer high electrical mobility (~153
      cm(2) V(-1) s(-1)) and scattering resistant carriers. Ultrathin 3-5 SLs PbBi2Se4
      shows an n-type semiconducting behaviour with a band gap of ~0.6 eV, which is
      confirmed by optical spectroscopy and thermopower measurements. 

PMID- 24916419
TI  - Multimodality imaging of the effects of a novel dentifrice on oral biofilm.
AB  - OBJECTIVE: Oral biofilm formation and progression on the surface of the tooth can
      lead to advanced oral disease such as gingivitis. The purpose of this randomized,
      controlled, double-blinded study was to evaluate the effects of a novel dental
      gel on oral plaque biofilm using multimodal imaging techniques. MATERIALS AND
      METHODS: Twenty-five subjects with moderate gingival inflammation (Loe and
      Silness Gingival Index >=2) and pocket depths <4 were randomly assigned to brush
      twice daily for 21 days with the test or the control dental gel. In vivo
      multimodality in situ imaging was performed over a 3-week period using in vivo
      Optical Coherence Tomography (OCT) and Non-Linear Optical microscopy (NLOM).
      Plaque levels, gingival inflammation and gingival bleeding were also charted on
      days 0, 7, 14, and 21 using standard clinical indices. RESULTS: After 3 weeks,
      OCT and NLOM images showed a macroscopic break-up of the plaque layer and
      smaller, fragmented residual deposits in the test group with no apparent changes
      in the pellicle. Biofilm was also reduced in the control group, but to a lesser
      degree with regard to thickness, continuity and surface area. Paralleling these
      imaging results, clinical indices were significantly improved in both groups (P <
      0.05) and significantly lower in the test group (P < 0.05). CONCLUSION: Both
      dental gels reduced oral biofilm with the test gel showing greater efficacy (P <
      0.05) as determined by clinical and imaging parameters.

PMID- 24916420
TI  - Temporary abdominal closure with polytetrafluoroethylene prosthetic mesh in
      critically ill non-trauma patients.
AB  - BACKGROUND: Survival in critically ill non-trauma patients may be improved by
      performing temporary abdominal closure using different surgical techniques. We
      describe the use of expanded polytetrafluoroethylene (ePTFE) mesh for temporary
      abdominal closure in a group of critical patients. We also evaluate definitive
      abdominal wall closure in these patients once they are in a stable condition.
      METHOD: We conducted a study of 29 critically ill non-trauma patients who
      underwent temporary abdominal closure due to sepsis or abdominal compartment
      syndrome over 7 years at two university hospitals. We analysed factors related to
      surgical wound type and definitive abdominal wall closure. We evaluated the SAPS
      3 severity score and used it to obtain expected mortality. We used the Clavien
      Dindo System for Surgical Complications and the Ventral Hernia Working Group
      Classification during follow-up. RESULTS: Performing temporary abdominal closure
      with expanded polytetrafluoroethylene mesh was associated with a mortality rate
      of 20.68%, which was lower than the expected mortality calculated from the SAPS 3
      severity score (38.87 +/- 21.60). There was no fistula formation related with
      this type of prosthetic material. In our study group, definitive abdominal wall
      closure was performed in the 16 patients who survived (69.5%), and six of them
      underwent this procedure during the original hospital stay. CONCLUSION: Temporary
      abdominal closure with ePTFE mesh is an effective alternative in some
      circumstances. We observed a higher survival rate than the predicted figure and
      there were no cases of enteroatmospheric fistulae using this particular surgical
      technique. ePTFE facilitates definitive abdominal wall closure, once the patient
      is in a stable condition.

PMID- 24916421
TI  - Wound dehiscence: outcome comparison for sutured and mesh reconstructed patients.
AB  - PURPOSE: Treatment guidelines for abdominal wound dehiscence (WD) are lacking.
      The primary aim of the study was to compare suture to mesh repair in WD patients
      concerning incisional hernia incidence. Secondary aims were to compare recurrent
      WD, morbidity, mortality and long-term abdominal wall complaints. METHODS: A
      retrospective chart review of 46 consecutive patients operated for WD between
      January 2010 and August 2012 was conducted. Physical examination and a
      questionnaire enquiry were performed in January 2013. RESULTS: Six patients were
      treated by vacuum-assisted wound closure and mesh-mediated fascial traction
      (VAWCM) before definitive closure. Three patients died early resulting in 23
      patients closed by suture and 20 by mesh repair. Five sutured, but no mesh repair
      patients had recurrent WD (p = 0.051) with a mortality of 60 %. Finally, 18
      sutured and 21 mesh repair patients were eligible for follow-up. The incidence of
      incisional hernia was higher for the sutured patients (53 vs. 5 %, p = 0.002),
      while mesh repair patients had a higher short-term morbidity rate (76 vs. 28 %, p
      = 0.004). Abdominal wall complaints were rare in both groups. CONCLUSIONS: Suture
      of WD was afflicted with a high incidence of recurrent WD and incisional hernia
      formation. Mesh repair overcomes these problems at the cost of more wound
      complications. VAWCM seems to be an alternative for treating contaminated
      patients until definitive closure is possible. Long-term abdominal wall
      complaints are uncommon after WD treatment.

PMID- 24916422
TI  - Determination of synthetic dyes in bean and meat products by liquid
      chromatography with tandem mass spectrometry.
AB  - A sensitive and efficient method was developed for the simultaneous determination
      of eight synthetic dyes (Chrysoidin, Auramine O, Sudan(I-IV), Para Red, and
      Rhodamine B) in bean and meat products using high-performance liquid
      chromatography with tandem mass spectrometry. A simple extraction procedure using
      acetonitrile has been applied for the extraction of these dyes from spiked bean
      and meat samples. Chromatographic separation was achieved on a Waters XTerra C18
      column (2.1 * 150 mm, 5 MUm) with a multistep gradient elution. Detection and
      quantification were performed using mass spectrometry in multiple reaction
      monitoring mode. Linear calibrations were obtained with correlation coefficients
      R(2) > 0.99. The limits of detection and quantification for the eight dyes were
      in the ranges of 0.03-0.75 and 0.1-2.0 MUg/kg depending on matrices,
      respectively. The recoveries of these dyes in different food matrices were
      between 71.2 and 116.9% with relative standard deviations <15.2%, suggesting that
      the developed method is promising for the accurate quantification of the eight
      dyes at trace levels in bean and meat products. 

PMID- 24916423
TI  - Synthetic anionophores for basic anions as "presumably, OH-/Cl- antiporters":
      from the synthetic ion channels to multi-ion hopping, anti-Hofmeister
      selectivity, and strong positive AMFE.
AB  - We describe application of theory and kinetic modeling to study transport of
      basic anions by the small synthetic molecules. The findings should equip
      researchers in the particular field with a tool necessary to address an essential
      question: whether a given anion transporter facilitates permeation of F(-),
      CH3COO(-), N3(-), and SCN(-) across biological membrane or it does not. The basic
      anions undergo hydrolysis and conjugate acids (HAnion) are permeant species.
      However, because methods to quantitatively account for HAnion transport do not
      exist, traditionally, the phenomenon is also treated as non-existing. When the
      relative activities and selectivity of the synthetic anionophores are evaluated,
      basic and non-basic anions are regarded in the same exact way. Here, we show that
      HAnion and H(+)/OH(-) transport proceed on the same time scale as the anion
      exchange, nevertheless, comprehensive kinetic study could provide solution to the
      problems at hands, such as selective transport of HCO3(-) or F(-) anions. We also
      use theory and modeling to study other questions of particular concern: transport
      of OH(-) and H(+) ions, facilitated by the small synthetic anionophore, origin of
      modified anti-Hofmeister selectivity, multi-ion hopping, and anomalous mole
      fraction effect in the synthetic ion channels. We do not need to model kinetics
      in a synthetic channel with multiple ion binding sites. Instead, we "test" the
      most simple anionophore, a lipophilic electroneutral carrier with Hofmeister-like
      selectivity, in the classical assays as "presumably, Cl(-)/OH(-) antiporter." The
      implications of findings to the particular field and beyond are discussed.

PMID- 24916424
TI  - Shifting sands - from descriptions to solutions.
AB  - BACKGROUND: Public health practitioners and policymakers value research evidence
      as one of many resources to use in evidence-informed decision making (EIDM) for
      public health. However, both researchers and decision-makers have described
      persistent barriers and facilitators involved in using research evidence for
      public health practice and policy. This is likely to affect the extent to which
      research evidence is influential or useful in decisions. Numerous taxonomies,
      typologies and frameworks are available to guide action in EIDM, but their
      application in practice is relatively unknown. METHODS: The Public Health
      Evidence group based in Australia, which incorporates The Cochrane
      Collaboration's Public Health Review Group, have adapted a number of
      conceptualizations of research use and types of evidence into a practical
      typology that defines and illustrates three main types of evidence used in
      evidence-informed public health: data (Type 1), intervention effectiveness (Type
      2) and implementation evidence (Type 3). The authors have actively used this
      typology within our primary research, evidence synthesis, workforce development
      and stakeholder engagement strategies, which has enabled practical application of
      these concepts. To test the relevance of the typology in practice, relevant
      findings from our applied research and evaluation (including two exploratory
      studies of evidence use in decision-making and evaluations of the use and impact
      of systematic reviews among end-users) were triangulated. RESULTS: The typology
      has been useful in stakeholder interactions when defining evidence, and
      identifying processes for EIDM. There was a preference for defining evidence as
      descriptive evidence (data) rather than impact evidence and implementation
      evidence. Practitioners were confident and competent at generating and using data
      and community views descriptively for priority setting (describing the problem).
      However, finding and using impact and implementation evidence appropriate for
      strategy development (effective solutions) was often described as a more daunting
      task. As a result, there was low awareness of, and competence with, Types 2 and 3
      evidence. Organizational processes for using these types of evidence were almost
      non-existent. DISCUSSION: Applying this typology with stakeholders has allowed us
      to observe that it; (1) has been useful in conceptualizing useful evidence for
      public health, which has guided our work (2) has been useful in stakeholder
      interactions to introduce evidence, its definition and what it means to be
      'evidence-informed' and (3) has identified 'faults' in the EIDM approach. The
      typology includes examples of common questions in public health, and suggestions
      of the types of evidence that may be useful to answer those questions. Findings
      that test the use of the typology have been synthesized. These have demonstrated
      inconsistencies in defining and applying evidence, and low awareness about what
      types of evidence are crucial to ensure that interventions are effective and
      minimize harm. Based upon these findings, the authors would argue that current
      investment in type 1 evidence (e.g. data repositories) shifts to make way for KT
      strategies, which facilitate the uptake of type 2 and 3 evidence (interventions
      and implementation guidance). CONCLUSIONS: Building a shared understanding of the
      types of evidence and their importance in public health decision-making is
      crucial if we wish to build a system that supports EIDM and results in effective
      interventions being delivered. There are a number of 'faults' in the system which
      the authors have illuminated through understanding the individual and
      organizational realities of evidence use. These faults could be addressed through
      KT strategies with the public health workforce, and development of organizational
      cultures and the broader system.

PMID- 24916425
TI  - Physical activity and healthy diet: determinants and implicit relationship.
AB  - OBJECTIVE: People who decide to lose weight by dieting often do so without
      participating in any associated physical activity. Although some people who
      participate in sports are unconcerned about their diet, it is generally believed
      that people who exercise tend to eat a healthy diet and those who do not exercise
      eat a less healthy diet. There is no clear relationship between the decisions
      regarding participation in physical activity and eating a healthy diet when
      choices are taken freely and not influenced by policy factors promoting healthy
      behaviour. However, these decisions may reveal some common explanatory factors
      and an implicit link. As such the aim of this study was to identify the common
      explanatory factors and investigate the existence of an implicit relationship.
      STUDY DESIGN: Econometric estimate - bivariate probit estimation. METHOD: Using
      data from the Portuguese National Health Survey, a bivariate probit was
      undertaken for decisions regarding participation in physical activity and eating
      a healthy diet. The correlation between the residuals gives information on the
      implicit relationship between the healthy choices. RESULTS: Common explanatory
      factors were found between the decisions to eat healthy snacks and participate in
      physical activity, such as being married. However, holding voluntary private
      health insurance, smoking, getting older, living alone and unemployment were
      found to dissuade people from making healthy choices. Positive correlation was
      found between the residuals of the probit estimations, indicating that other
      unmeasurable variables have a similar influence on both decisions, such as peer
      pressure, cultural values, fashion, advertising and risk aversion. CONCLUSIONS:
      Further research is needed to improve understanding of decision making related to
      participation in physical activity and eating a healthy diet. This will
      facilitate the design of policies that will make a greater contribution to
      healthy lifestyles.

PMID- 24916426
TI  - Acne vulgaris: prevalence, beliefs, patients' attitudes, severity and impact on
      quality of life in Egypt.

PMID- 24916427
TI  - Opportunistic community-based health checks.

PMID- 24916428
TI  - Biliary tract cancer in male printers and typesetters in the European rare cancer
      case-control study.

PMID- 24916429
TI  - Transfemoral liver biopsy using a Quick-Core biopsy needle system in living donor
      liver transplantation recipients.
AB  - The purpose of this study was to evaluate the efficacy and safety of transfemoral
      liver biopsy with a Quick-Core biopsy needle in select living donor liver
      transplantation (LDLT) recipients. Eight LDLT recipients underwent 9 transfemoral
      liver biopsy sessions. Six patients had undergone modified right lobe (mRL) LDLT,
      and 2 patients had undergone dual-left lobe LDLT. The indications for
      transfemoral liver biopsy were a hepatic vein (HV) at an acute angle to the
      inferior vena cava (IVC) on the coronal plane and a thin (<10-mm) liver
      parenchyma surrounding the HV to be biopsied on enhanced computed tomography.
      Under fluoroscopic guidance, the right inferior HV in the mRL or the left HV in
      the right-sided left lobe with a cranial orientation was negotiated with a 5-Fr
      catheter via the common femoral vein. Then, a stiffening cannula was introduced
      into the HV over a stiff guide wire. Needle passage was then performed with an 18
      or 19-gauge Quick-Core biopsy needle. Technical success was achieved in all
      sessions without major complications. The median number of needle passages was 4
      (range = 2-6). The median total length of obtained liver specimens in each
      session was 44 mm (range = 24-75 mm). The median number of portal tracts was 18
      (range = 10-29), and the obtained liver specimens were adequate for histological
      diagnosis in all sessions. In conclusion, transfemoral liver biopsy with a Quick
      Core biopsy needle is an effective and safe alternative for obtaining a liver
      specimen when standard transjugular liver biopsy is not feasible because of an
      unfavorable HV angle with respect to the IVC and/or a thin liver parenchyma
      surrounding the HV.

PMID- 24916430
TI  - Mitochondrial disease: clinical aspects, molecular mechanisms, translational
      science, and clinical frontiers.
AB  - Mitochondrial medicine provides a metabolic perspective on the pathology of
      conditions linked with inadequate oxidative phosphorylation. Dysfunction in the
      mitochondrial machinery can result in improper energy production, leading to
      cellular injury or even apoptosis. Clinical presentations are often subtle, so
      clinicians must have a high index of suspicion to make early diagnoses. Symptoms
      could include muscle weakness and pain, seizures, loss of motor control,
      decreased visual and auditory functions, metabolic acidosis, acute developmental
      regression, and immune system dysfunction. The 2013 Neurobiology of Disease in
      Children Symposium, held in conjunction with the 42nd Annual Meeting of the Child
      Neurology Society, aimed to (1) describe accepted clinical phenotypes of
      mitochondrial disease produced from various mitochondrial mutations, (2) discuss
      contemporary understanding of molecular mechanisms that contribute to disease
      pathology, (3) highlight the systemic effects produced by dysfunction within the
      mitochondrial machinery, and (4) introduce current strategies that are being
      translated from bench to bedside as potential therapeutics. 

PMID- 24916431
TI  - Successful pacing using a batteryless sunlight-powered pacemaker.
AB  - AIMS: Today's cardiac pacemakers are powered by batteries with limited energy
      capacity. As the battery's lifetime ends, the pacemaker needs to be replaced.
      This surgical re-intervention is costly and bears the risk of complications.
      Thus, a pacemaker without primary batteries is desirable. The goal of this study
      was to test whether transcutaneous solar light could power a pacemaker. METHODS
      AND RESULTS: We used a three-step approach to investigate the feasibility of
      sunlight-powered cardiac pacing. First, the harvestable power was estimated.
      Theoretically, a subcutaneously implanted 1 cm(2) solar module may harvest ~2500
      uW from sunlight (3 mm implantation depth). Secondly, ex vivo measurements were
      performed with solar cells placed under pig skin flaps exposed to a solar
      simulator and real sunlight. Ex vivo measurements under real sunlight resulted in
      a median output power of 4941 uW/cm(2) [interquartile range (IQR) 3767-5598
      uW/cm(2), median skin flap thickness 3.0 mm (IQR 2.7-3.3 mm)]. The output power
      strongly depended on implantation depth (rhoSpearman = -0.86, P < 0.001).
      Finally, a batteryless single-chamber pacemaker powered by a 3.24 cm(2) solar
      module was implanted in vivo in a pig to measure output power and to pace. In
      vivo measurements showed a median output power of >3500 uW/cm(2) (skin flap
      thickness 2.8-3.84 mm). Successful batteryless VVI pacing using a subcutaneously
      implanted solar module was performed. CONCLUSION: Based on our results, we
      estimate that a few minutes of direct sunlight (irradiating an implanted solar
      module) allow powering a pacemaker for 24 h using a suitable energy storage.
      Thus, powering a pacemaker by sunlight is feasible and may be an alternative
      energy supply for tomorrow's pacemakers.

PMID- 24916432
TI  - The mammalian target of rapamycin pathway in the basolateral amygdala is critical
      for nicotine-induced behavioural sensitization.
AB  - Repeated exposure to nicotine increases psychomotor activity. Long-lasting neural
      plasticity changes that contribute to the nicotine-induced development of
      locomotor sensitization have been identified. The mammalian target of rapamycin
      complex 1 (mTORC1) signalling pathway is involved in regulating the
      neuroplasticity of the central nervous system. In this study, we examined the
      role of mTORC1 in the amygdala in nicotine-induced locomotor sensitization.
      Rapamycin, an inhibitor of mTORC1, was infused into the basolateral amygdala
      (BLA) and central amygdala (CeA) or systemically administered to investigate the
      role of the mTORC1 in the development and expression of nicotine-induced
      locomotor sensitization. We found that locomotor activity progressively increased
      during the initiation of nicotine-induced locomotor sensitization and the
      expression of nicotine sensitization was induced by nicotine challenge injection
      (0.35 mg/kg s.c.) after five days of withdrawal. The initiation of nicotine
      induced locomotor sensitization was accompanied by the increased phosphorylated
      level of mTORC1 downstream target proteins including p-p70s6k and p-4EBP in the
      BLA, but not CeA. Intra-BLA infusion or systemic administration of rapamycin
      blocked locomotor activity. Increased p-p70s6k and p-4EBP were also observed in
      the expression of nicotine sensitization, which was demonstrated to be inhibited
      by systemic rapamycin administration. Our findings indicated that mTORC1 activity
      in the BLA, but not the CeA, mediated the initiation and expression of nicotine
      induced locomotor sensitization, and may become a potential target for the
      treatment of nicotine addiction. 

PMID- 24916433
TI  - The CROWN Initiative: Journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 24916434
TI  - Implementing the ESHRE 'poor responder' criteria in research studies:
      methodological implications.
AB  - The Bologna criteria for defining poor ovarian response (POR) during IVF provide
      a useful template for new research in this field of assisted conception. However,
      designing studies around the European Society for Human Reproduction and
      Embryology POR criteria can be methodologically challenging, as the new
      definition includes various POR subpopulations with diverse baseline
      characteristics and unknown clinical prognosis. When designing RCTs, potential
      result bias may be introduced if women from each subpopulation are not evenly
      allocated between intervention groups. In the case of small or moderate-size
      RCTs, a single-sequence randomization method may not ensure balanced allocation
      between groups. Stratified randomization methods provide an alternative
      methodological approach. Depending on the chosen methodology, patient
      characteristics and outcomes within each intervention group may be better
      reported according to relevant subpopulations. 

PMID- 24916435
TI  - Deciding about fertility preservation after specialist counselling.
AB  - STUDY QUESTION: How do female patients experience fertility preservation (FP)
      consultation (FPC) with a specialist in reproductive medicine and subsequent
      decision-making on FP? SUMMARY ANSWER: Most patients had positive experiences
      with FPC, but negative experiences were found to be associated with decisional
      conflict and decision regret. WHAT IS KNOWN ALREADY: When confronted with a need
      for gonadotoxic treatment, girls and young women will have to make an
      irreversible decision with regard to FP. Patients may experience decisional
      conflict and develop regret about their decision during follow-up. Patients'
      opportunities to ask questions during FPC and their knowledge about FP have been
      inversely related to decisional conflict. STUDY DESIGN, SIZE, DURATION: A
      questionnaire on experiences with FPC, designed after qualitative research, was
      retrospectively distributed to 108 patients to whom FP was offered after FPC
      between July 2008 and July 2013. Aiming to minimize recall bias, we defined a
      subgroup of patients counselled since 2011 who had not yet tried to conceive
      after FPC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were aged >=16
      years and had either cancer or a benign disease that required gonadotoxic
      therapy. They received FPC in a single university hospital in the Netherlands.
      Apart from patients' experiences, patients' characteristics, decisional conflict
      and decision regret were assessed. MAIN RESULTS AND ROLE OF CHANCE: A total of 64
      patients (59.3%) responded to the questionnaire. Patients generally had positive
      experiences with FPC, but indicated room for improvement. Negative experiences
      were associated with decisional conflict regarding the FP decision (not enough
      time for counselling: P < 0.0001; not having the opportunity to ask all questions
      during FPC: P < 0.0001; not feeling supported by the counsellor during decision
      making: P = 0.0003; not all applicable options were discussed: P = 0.0001;
      benefits and disadvantages of FP options were not clearly explained: P = 0.0005).
      Decisional conflict was correlated to decision regret (P < 0.0001). In the
      subgroup of patients counselled after 2011 who had not tried to conceive (n =
      33), similar results as for the total study population were found for the
      association of patient experiences with decisional conflict. LIMITATIONS, REASONS
      FOR CAUTION: Given our retrospective design, we were not informed about the
      causality of the associations observed. We studied Dutch patients who were
      counselled in a single centre and were at least 16 years old when filling in the
      questionnaire. This may limit the generalizability of our data to other settings
      and populations. WIDER IMPLICATIONS OF THE FINDINGS: More attention should be
      paid to improving FPC care. Interventions aiming at improving patients'
      comprehension of the topic of FP and their feelings of being supported in
      decision-making are advisable. STUDY FUNDING/COMPETING INTERESTS: This work was
      supported by the Radboud Institute for Health and an unconditional grant from
      Merck Serono. The authors have declared no conflicts of interest with respect to
      this work.

PMID- 24916436
TI  - Timing of contraceptive initiation and association with future sexual and
      reproductive outcomes.
AB  - STUDY QUESTION: Who initiates contraception before, at the time or after first
      sexual intercourse and how does timing of initiation affect future sexual and
      reproductive health (SRH) outcomes? SUMMARY ANSWER: Earlier initiation was
      associated with current utilization of more effective contraception, but had no
      impact on future unintended pregnancy, abortion or sexually transmitted infection
      rates, while later initiation was linked to higher rates of unintended
      pregnancies and abortions. WHAT IS KNOWN ALREADY: Contraceptive behaviour at
      first intercourse is associated with later SRH outcomes. STUDY DESIGN, SIZE,
      DURATION: Data were drawn from the FECOND study, the last national SRH study in
      France, conducted in 2010-2011 by phone among 8645 individuals aged 15-49 years.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Analysis was performed among 1552 women
      under the age of 30 years who were sexually experienced and had used
      contraception at some point. We used logistic regression models to identify
      factors associated with timing of contraception initiation relative to first
      intercourse (earlier, at the time and later) and its predictive value on future
      sexual and reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Timing of
      contraceptive initiation across all three categories (earlier, at the time and
      later initiators) was dependent on women's age at the time of the survey, country
      of birth, education level, ease of discussing sex with mother and age of first
      sex. Using at the time initiators as a reference, later initiators had higher
      odds of unintended pregnancy [odds ratio (OR) = 1.8] and abortion (OR = 1.9),
      while earlier initiators were more likely to be using more effective
      contraception at the time of the survey (OR = 1.8). LIMITATIONS, REASONS FOR
      CAUTION: The exclusion of sexually inexperienced women, a quarter of which had
      ever used the pill, may have reduced the scope of our analysis on the relevance
      of contraceptive initiation for non-contraceptive benefits. WIDER IMPLICATIONS OF
      THE FINDINGS: The promotion of early initiation of contraception may contribute
      to long-term use of more effective methods of contraception. STUDY
      FUNDING/COMPETING INTERESTS: The FECOND study was supported by a grant from the
      French Ministry of Health, a grant from the French National Agency of Research
      (#ANR-08-BLAN-0286-01; PIs N. Bajos, C Moreau) and funding from the National
      Institute of Health and Medical Research (INSERM) and the National Institute for
      Demographic Research (INED). None of the authors have a conflict of interest.

PMID- 24916437
TI  - Circumstances of falls and fall-related injuries among patients with Parkinson's
      disease in an outpatient setting.
AB  - Falls represent continuing, disabling and costly problem in Parkinson's disease
      (PD). The study was carried out at the Neurology Clinic in Belgrade from August
      2011 to December 2012. As many as 180 community dwelling persons with PD aged 22
      83 years who sustained a fall in past 6 months were included. Characteristics of
      the most recent fall were obtained through detailed interviews. Inclusion
      criteria were: Mini Mental State Examination (MMSE)>=24, ability to walk
      independently for at least 10 m and ability to statically stand for at least 90
      s. Exclusion criteria were: presence of other neurologic as well as psychiatric,
      visual, audio-vestibular and orthopedic impairments. Falls more frequently took
      place outside (57.2%) and in the morning (53.9%). As much as 38.9% of persons
      with PD sustained an injury. Soft-tissue contusion was the most common injury
      (71.8%) both after indoor and outdoor falls. Fractures accounted for 5% of all
      fall-related injuries. All the fractures were either arm, clavicle or rib
      fractures. Tripping was identified as risk factor for outdoor falls (OR=7.90; 95%
      confidence interval [95% CI] 3.21-19.39; p=0.001). In contrast, lower extremity
      weakness (OR=0.20; 95% CI 0.05-0.72; p=0.015) and internal sense of sudden loss
      of balance (OR=0.19; 95% CI 0.05-0.73; p=0.015) were risk factors for indoor
      falls. To accomplish long-term results, development of particular prevention
      programs for persons with PD who fall at home vs. outdoors is recommended.

PMID- 24916438
TI  - Observation of inflammatory responses in mice orally fed with bacteriophage T7.
AB  - AIMS: Analysis of inflammatory immune response upon bacteriophage intake in mice.
      METHODS AND RESULTS: Bacteriophage therapy is emerging as an effective
      alternative to conventional antibiotics. However, its safety when applied to
      humans and animals remains a prime concern. This study investigated the
      inflammatory responses in mice fed orally with bacteriophages. The mice were fed
      with either murine norovirus (MNV) or bacteriophage T7 for 10 days and then
      sacrificed. No behavioural changes related to diet, movement or defecation were
      observed in either group. The inflammatory cytokine profiling showed an increased
      level of interleukins 1alpha (IL-1alpha), 1beta (IL-1beta), 2 (IL-2), 10 (IL-10),
      12 (IL-12), 17A (IL-17A), interferon-gamma (IFN-gamma), tumour necrosis factor
      alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) in the serum from the mice fed with
      MNV, whereas only a slight increase in IL-17A was observed in the serum from the
      mice fed with bacteriophage T7. A histopathological analysis of tissue samples
      from the stomach, small intestine and colon revealed no significant pathological
      change. CONCLUSIONS: The bacteriophage diet only caused a minimal inflammatory
      response in the mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides
      insights into safety concerns of orally fed bacteriophage therapy.

PMID- 24916439
TI  - Isotretinoin therapy changes the expression of antimicrobial peptides in acne
      vulgaris.
AB  - In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e.,
      protective by acting against Propionibacterium acnes, pro-inflammatory by acting
      as signalling molecules. The cutaneous expression of 15 different AMPs was
      investigated in acne patients; furthermore, the impact of isotretinoin therapy on
      AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris
      taken before, during and after a 6-month treatment cycle with isotretinoin using
      quantitative real-time polymerase chain reaction. Cutaneous expression of the
      AMPs cathelicidin, human beta-defensin-2 (HBD-2), lactoferrin, lysozyme,
      psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in
      untreated acne vulgaris, whereas alpha-defensin-1 (HNP-1) was downregulated
      compared to controls. While relative expression levels of cathelicidin, HBD-2,
      lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during
      isotretinoin treatment, only those of cathelicidin and koebnerisin returned to
      normal after 6 months of isotretinoin therapy. The increased expression of
      lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of
      granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and
      dermcidin were not regulated in untreated acne patients and isotretinoin had no
      effect on these AMPs. In conclusion, the expression of various AMPs is altered in
      acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of
      distinct AMPs while the expression of others is still increased in healing acne.
      Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules
      could serve as specific targets for acne therapy and maintenance of clinical
      remission.

PMID- 24916441
TI  - Gluconate 5-dehydrogenase (Ga5DH) participates in Streptococcus suis cell
      division.
AB  - Bacterial cell division is strictly regulated in the formation of equal daughter
      cells. This process is governed by a series of spatial and temporal regulators,
      and several new factors of interest to the field have recently been identified.
      Here, we report the requirement of gluconate 5-dehydrogenase (Ga5DH) in cell
      division of the zoonotic pathogen Streptococcus suis. Ga5DH catalyzes the
      reversible reduction of 5-ketogluconate to D-gluconate and was localized to the
      site of cell division. The deletion of Ga5DH in S. suis resulted in a plump
      morphology with aberrant septa joining the progeny. A significant increase was
      also observed in cell length. These defects were determined to be the consequence
      of Ga5DH deprivation in S. suis causing FtsZ delocalization. In addition, the
      interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction
      assays. These results indicate that Ga5DH may function to prevent the formation
      of ectopic Z rings during S. suis cell division. 

PMID- 24916442
TI  - Whole genome sequencing and phylogenetic analysis of Bluetongue virus serotype 2
      strains isolated in the Americas including a novel strain from the western United
      States.
AB  - Bluetongue is a potentially fatal arboviral disease of domestic and wild
      ruminants that is characterized by widespread edema and tissue necrosis.
      Bluetongue virus (BTV) serotypes 10, 11, 13, and 17 occur throughout much of the
      United States, whereas serotype 2 (BTV-2) was previously only detected in the
      southeastern United States. Since 1998, 10 other BTV serotypes have also been
      isolated from ruminants in the southeastern United States. In 2010, BTV-2 was
      identified in California for the first time, and preliminary sequence analysis
      indicated that the virus isolate was closely related to BTV strains circulating
      in the southeastern United States. In the current study, the whole genome
      sequence of the California strain of BTV-2 was compared with those of other BTV-2
      strains in the Americas. The results of the analysis suggest co-circulation of
      genetically distinct viruses in the southeastern United States, and further
      suggest that the 2010 western isolate is closely related to southeastern strains
      of BTV. Although it remains uncertain as to how this novel virus was translocated
      to California, the findings of the current study underscore the need for ongoing
      surveillance of this economically important livestock disease.

PMID- 24916443
TI  - Outbreak of Bluetongue virus serotype 4 in dairy sheep in Rio de Janeiro, Brazil.
AB  - In late January 2013, 10 nonpregnant Lacaune dairy ewes raised under extensive
      husbandry management on a farm in Rio de Janeiro, Brazil, presented with the
      general clinical signs of lethargy, hyporexia, edema of the face, hyperemia of
      the exposed parts of the skin, mouth lesions, pyrexia, and lameness.
      Additionally, 2 pregnant ewes died suddenly after the onset of respiratory signs.
      The complete blood counts and biochemistry analyses showed neutrophilic
      leukocytosis with monocytosis and reactive lymphocytes, normocytic normochromic
      anemia and increased aspartate aminotransferase levels. Postmortem examination
      revealed erosions on the lingual mucosa, bilateral submandibular ganglia
      infarctions, yellow foamy fluid accumulation in the trachea and bronchial
      bifurcation, pulmonary congestion, and edema associated with hemorrhagic lesions
      on the pulmonary artery and heart. The clinical and pathological findings were
      suggestive of bluetongue. For a molecular and virological diagnosis, tissue
      samples were analyzed by Bluetongue virus-specific real-time reverse
      transcription polymerase chain reaction (qRT-PCR), and viral isolation was
      performed in embryonated chicken eggs. For viral typing, positive tissue and egg
      isolated samples were analyzed by qRT-PCR using primers and probes specific for
      the structural VP2 gene in genome segment 2 of all 26 serotypes. There are still
      no contingency plans for responding to an outbreak of bluetongue disease in
      Brazil, and this episode emphasizes the need for continuing serological and
      entomological surveillance programs. Additionally, this report describes the
      isolation of Bluetongue virus serotype 4 in sheep in the Americas.

PMID- 24916440
TI  - The genetic and epigenetic alterations in human hepatocellular carcinoma: a
      recent update.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies
      worldwide with very poor prognosis. It is generally accepted that the progression
      of HCC is a long-term process with accumulation of multiple genetic and
      epigenetic alterations, which further lead to the activation of critical
      oncogenes or inactivation of tumor suppressor genes. HCC is characterized with
      multiple cancer hallmarks including their ability to proliferate, anti-apoptosis,
      invade, metastasis, as well as the emerging features such as stem cell properties
      and energy metabolic switch. The irreversible alterations at genetic level could
      be detected as early as in the pre-neoplastic stages and accumulate during cancer
      progression. Thus, they might account for the cancer initiating steps and further
      malignant transformation. In addition to genetic alterations, epigenetic
      alterations can affect the cancer transcriptome more extensively. Alterations in
      DNA methylation, histone modification, miRNAs, RNA editing, and lncRNAs might
      result in disrupted gene regulation networks and substantially contribute to HCC
      progression. In this review, the genetic and epigenetic alterations which
      significantly contribute to the malignant capabilities of HCC will be updated and
      summarized in detail. Further characterization of those critical molecular events
      might better elucidate the pathogenesis of HCC and provide novel therapeutic
      targets for treatment of this deadly disease. 

PMID- 24916444
TI  - Use of the polymerase chain reaction assay for the detection of Babesia odocoilei
      18S ribosomal RNA in formalin-fixed tissues.
AB  - The effect of fixation and storage conditions on the performance of polymerase
      chain reaction (PCR) assays for Babesia odocoilei were examined using 3 different
      primer sets targeting the eukaryotic 18S ribosomal RNA gene, with variably sized
      products of 1,723 base pairs (bp), 483 bp, and 306 bp. All primer sets performed
      well on fresh-frozen tissue, and storage for 1 year at -20 degrees C did not
      affect PCR performance. Formalin fixation markedly affected the amplicon length
      that could be amplified. However, DNA was successfully amplified after storage in
      formalin for 2 months using the primer set with a 483-bp product, and up to 6
      months using the primer set with a 306-bp product. The latter primer set
      successfully differentiated B. odocoilei and Babesia microti DNA; however,
      further evaluation is required to confirm its specificity. Treatment of tissues
      with formic acid, at concentrations typically used to denature prions, degraded
      the DNA and made it unsuitable for PCR testing.

PMID- 24916445
TI  - Touchdown polymerase chain reaction detection of polycystic kidney disease and
      laboratory findings in different cat populations.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent
      inherited genetic disease of cats, predominantly affecting Persian and Persian
      related cats. A point mutation (C->A transversion) in exon 29 of the PKD1 gene
      causes ADPKD, and is the specific molecular target for genetic diagnosis in cats.
      The current study describes a newly developed touchdown polymerase chain reaction
      (PCR) to detect this single point mutation, using 2 primers specific for the
      mutant allele, adapted from an existing multiplex amplification refractory
      mutation system (ARMS PCR). Furthermore, correlations between the clinical
      outcomes of tested animals and the results of the genetic test were investigated.
      A total of 334 cats were tested, 188 from the Veterinary Hospital of Small
      Animals at the University of Brasilia, and 146 from an anti-rabies vaccine
      campaign of the Federal District. A total prevalence of 9% was evident among the
      samples, with 33% of the Persian cats testing positive, and 7% of the Brazilian
      long- and shorthaired cats testing positive. Prevalence was not correlated with
      gender or hemogram. Positive animals exhibited hyperglobulinemia ( P = 0.02).
      This research demonstrated that the mutation does not only occur in Persian and
      Persian-related cats, and that a touchdown PCR can be used to diagnose ADPKD.

PMID- 24916446
TI  - PCB 126 perturbs hypoxia-induced HIF-1alpha activity and glucose consumption in
      human HepG2 cells.
AB  - Aerobic organisms strongly depend on the availability of oxygen for respiration
      and countless other metabolic processes to maintain cellular homeostasis. Under
      certain conditions, the amount of available oxygen can be limited. To support
      survival in environments with limited oxygen supply, hypoxia-inducible factors
      (HIFs) reprogram vital components of cellular metabolism. HIF-1alpha is an
      important mediator of acute and adaptive responses to hypoxic stress.
      Interestingly, the heterodimeric partner required by HIF-1alpha to function as
      transcription factor, known as ARNT, is also an essential part of the aryl
      hydrocarbon receptor (AhR) transcription factor complex. Thus, via ARNT a
      crosstalk exists between these two pathways that might affect HIF-1alpha-mediated
      processes. In this study we sought to assess the effect of the AhR agonist PCB
      126 on HIF-1alpha activity as well as on HIF-1alpha-regulated targets involved in
      cellular metabolism in human HepG2 cells. Our results show that PCB 126 reduced
      HIF-1alpha localization to the nucleus. Furthermore, in an in vivo setting, rats
      exposed to parenteral PCB 126 also displayed reduced hepatocyte nuclear
      localization of HIF-1alpha. Additionally, HepG2 cells exposed to PCB 126
      displayed reduced hypoxia-regulated HRE-luciferase reporter gene expression as
      well as a reduction in glucose consumption in conditions of hypoxia. In summary,
      this study reveals that HIF-1alpha-regulated cellular metabolic processes are
      negatively affected by PCB 126 which might ultimately affect adaptive responses
      and cell survival in hypoxic environments. 

PMID- 24916447
TI  - Topical formulations containing finasteride. Part II: determination of
      finasteride penetration into hair follicles using the differential stripping
      technique.
AB  - The differential stripping technique consists of a tape-stripping phase followed
      by a cyanoacrylate biopsy. This technique not only allows the quantification of
      drug retained in the stratum corneum (SC) and in the hair follicles but also
      differentiates transepidermal from transfollicular penetration. Our study aimed
      at both validating the differential stripping procedure on hairless rat skin and
      assessing the role of the hair follicle in the cutaneous penetration of
      finasteride (FNS) after application of two experimental formulations for 6 or 24
      h: P-08-016, a hydroxypropyl chitosan (HPCH)-based formulation and P-10-008, an
      anhydrous formulation devoid of HPCH. Microscopic and histological evaluation
      showed that after 15 tape strips both the SC and the viable epidermis were
      completely removed. A subsequent cyanoacrylate skin surface biopsy led to the
      removal of the infundibula content. The largest amounts of FNS were found in the
      epidermis and in the appendages after application of P-08-016, regardless of the
      time from application. In contrast, smaller and statistically significant amounts
      of FNS were recovered with P-10-008 6 h after application, compared with that at
      24 h. In conclusion, the differential stripping technique allowed determination
      of the amount of FNS localized in different skin districts, focusing particularly
      on the follicular contribution.

PMID- 24916448
TI  - Clinical beak and feather disease virus infection in wild juvenile eastern
      rosellas of New Zealand; biosecurity implications for wildlife care facilities.
AB  - CASE HISTORY: Four juvenile eastern rosellas (Platycercus eximius) were admitted
      to two separate wildlife care facilities in the Auckland region by members of the
      public. They had missing or dystrophic wing and tail feathers that rendered them
      flightless, suggestive of beak and feather disease virus (BFDV) infection. Two
      were subject to euthanasia after failing to re-grow their feathers, with samples
      taken for histopathology and PCR analysis. Blood samples were obtained from the
      other two birds at the time of examination, however these individuals were lost
      to follow up. PATHOLOGICAL AND MOLECULAR FINDINGS: Basophilic inclusion bodies
      were observed in histological sections of the feather bulb, typical of BFDV
      infection, from the two euthanised individuals. Blood from all four birds tested
      positive by PCR for BFDV, and analysis of the recovered full BFDV genomes
      identified them as belonging to the BFDV-A strain. DIAGNOSIS: Beak and feather
      disease virus infection. CLINICAL RELEVANCE: This report highlights the clinical
      impacts of BFDV in juvenile eastern rosellas that may result in their admission
      to wildlife care facilities, creating a biosecurity risk in institutions that may
      host other native parrots intended for release. The environmental stability of
      BFDV and resistance to disinfection requires strict quarantine procedures to
      prevent contamination and spread within a facility. It is recommended that high
      risk species such as wild eastern rosella be excluded from facilities that may
      also house native parrots.

PMID- 24916449
TI  - Design and application of a real-time polymerase chain for the detection and
      subsequent characterization of respiratory adenoviral infections.
AB  - Human adenoviruses (HADVs) comprise at least 54 types and cause a wide spectrum
      of respiratory tract infections; early diagnosis and epidemiological monitoring
      of HADV infections requires a rapid and sensitive assay. The use of a real-time
      polymerase chain reaction (PCR) assay was evaluated with one set of in-house
      designed primers for respiratory adenoviral infections. The assay was first
      validated by detecting successfully 6 representative types and 100 clinical
      isolates. A concomitant prospective surveillance of viral aetiology using
      conventional cultures and PCR assays in 160 febrile children with acute
      respiratory tract symptoms was conducted between May 2010 and July 2011. Viral
      aetiologies were confirmed in 72 (45%) cases using conventional cultures,
      including 51 adenoviral infections. The concordance between the real-time PCR and
      culture was good (Kappa = 0.94), and two additional culture-negative adenovirus
      infections were identified. During the study period (January 2011), an adenoviral
      community epidemic occurred. Adenovirus B3 was the predominant type in this
      epidemic (69.8%), followed by C2 (5.7%), C1 (5.7%), C5 (1.9%), E4 (1.9%), C6
      (1.9%), F41 (1.9%), and 4 unclassified species C (7.5%). Significantly prolonged
      duration of fever (>5 days), higher leukocyte counts, higher neutrophil counts,
      and higher C-reactive protein levels were in the adenoviral infected group (n =
      53, P < 0.001), compared with the non-adenoviral infected group (n = 107). In
      conclusion, this in-house real-time PCR is capable of detecting adenoviral
      respiratory infections of various types in children; and patients with adenoviral
      aetiology suffered from more severe clinical manifestations.

PMID- 24916450
TI  - Depression and its measurement in verbal adolescents and adults with autism
      spectrum disorder.
AB  - In a sample of 50 verbally fluent adolescents and adults with autism spectrum
      disorders (age: 16-31 years; verbal IQ: 72-140), we examined the pattern of
      response and associations between scores on common measures of depressive
      symptoms, participant characteristics, and clinical diagnosis of depressive
      disorders. Beck Depression Inventory-Second Edition item descriptives in this
      autism spectrum disorder sample were compared to previously published data from a
      large typically developing sample, with results suggesting that cognitive
      attributional symptoms of depression may be particularly prevalent in autism
      spectrum disorder. Scores on a variety of self- and parent-report depression
      measures were not associated with chronological age or verbal IQ, and were
      relatively highly correlated with each other and with clinical diagnosis of a
      mood disorder. The Beck Depression Inventory-Second Edition and the Adult Self
      Report "Depressive" scale best identified both depressed and non-depressed
      participants in this sample, though neither was particularly strong. Validation
      studies of depression measures in the autism spectrum disorder population are
      necessary to advance research into this prevalent and impairing comorbidity. 

PMID- 24916451
TI  - Multimodal brain imaging in autism spectrum disorder and the promise of twin
      research.
AB  - Current evidence suggests the phenotype of autism spectrum disorder to be driven
      by a complex interaction of genetic and environmental factors impacting onto
      brain maturation, synaptic function, and cortical networks. However, findings are
      heterogeneous, and the exact neurobiological pathways of autism spectrum disorder
      still remain poorly understood. The co-twin control or twin-difference design is
      a potentially powerful tool to disentangle causal genetic and environmental
      contributions on neurodevelopment in autism spectrum disorder. To this end,
      monozygotic twins discordant for this condition provide unique means for the
      maximum control of potentially confounding factors. Unfortunately, only few
      studies of a rather narrow scope, and limited sample size, have been conducted.
      In an attempt to highlight the great potential of combining the brain connectome
      approach with monozygotic twin design, we first give an overview of the existing
      neurobiological evidence for autism spectrum disorder and its cognitive
      correlates. Then, a special focus is made onto the brain imaging findings
      reported within populations of monozygotic twins phenotypically discordant for
      autism spectrum disorder. Finally, we introduce the brain connectome model and
      describe an ongoing project using this approach among the largest cohort of
      monozygotic twins discordant for autism spectrum disorder ever recruited. 

PMID- 24916452
TI  - Iconicity influences how effectively minimally verbal children with autism and
      ability-matched typically developing children use pictures as symbols in a search
      task.
AB  - Previous word learning studies suggest that children with autism spectrum
      disorder may have difficulty understanding pictorial symbols. Here we investigate
      the ability of children with autism spectrum disorder and language-matched
      typically developing children to contextualize symbolic information communicated
      by pictures in a search task that did not involve word learning. Out of the
      participant's view, a small toy was concealed underneath one of four unique
      occluders that were individuated by familiar nameable objects or unfamiliar
      unnamable objects. Children were shown a picture of the hiding location and then
      searched for the toy. Over three sessions, children completed trials with color
      photographs, black-and-white line drawings, and abstract color pictures. The
      results reveal zero group differences; neither children with autism spectrum
      disorder nor typically developing children were influenced by occluder
      familiarity, and both groups' errorless retrieval rates were above-chance with
      all three picture types. However, both groups made significantly more errorless
      retrievals in the most-iconic photograph trials, and performance was universally
      predicted by receptive language. Therefore, our findings indicate that children
      with autism spectrum disorder and young typically developing children can
      contextualize pictures and use them to adaptively guide their behavior in real
      time and space. However, this ability is significantly influenced by receptive
      language development and pictorial iconicity. 

PMID- 24916453
TI  - Rethinking language in autism.
AB  - In this article, we invite a rethinking of traditional perspectives of language
      in autism. We advocate a theoretical reappraisal that offers a corrective to the
      dominant and largely tacitly held view that language, in its essence, is a
      referential system and a reflection of the individual's cognition. Drawing on
      scholarship in Conversation Analysis and linguistic anthropology, we present a
      multidimensional view of language, showing how it also functions as interactional
      accomplishment, social action, and mode of experience. From such a
      multidimensional perspective, we revisit data presented by other researchers that
      include instances of prototypical features of autistic speech, giving them a
      somewhat different-at times complementary, at times alternative-interpretation.
      In doing so, we demonstrate that there is much at stake in the view of language
      that we as researchers bring to our analysis of autistic speech. Ultimately, we
      argue that adopting a multidimensional view of language has wide ranging
      implications, deepening our understanding of autism's core features and
      developmental trajectory. 

PMID- 24916454
TI  - Measuring the lifetime of silicon nanocrystal solar cell photo-carriers by using
      Kelvin probe force microscopy and x-ray photoelectron spectroscopy.
AB  - We report the first measurements of photo-carrier lifetimes in silicon
      nanocrystal-based third generation solar cells by Kelvin force microscopy and x
      ray photoelectron spectroscopy under modulated frequency light illumination. A
      high concentration of active defects at the interface between the nanocrystals
      and silicon oxide matrix may be passivated by annealing under hydrogen. We found
      that the carrier lifetime, tau, is tau = 7 * 10(-5) s and tau = 3.5 * 10(-5) s
      within 10% accuracy for the hydrogen passivated and non-passivated nanocrystals,
      respectively. We used an exponential model to confirm the experimental potential
      measurements and to estimate photo-carrier lifetimes.

PMID- 24916455
TI  - Fresh versus frozen embryo transfer: backing clinical decisions with scientific
      and clinical evidence.
AB  - BACKGROUND: Improvements in vitrification now make frozen embryo transfers (FETs)
      a viable alternative to fresh embryo transfer, with reports from observational
      studies and randomized controlled trials suggesting that: (i) the endometrium in
      stimulated cycles is not optimally prepared for implantation; (ii) pregnancy
      rates are increased following FET and (iii) perinatal outcomes are less affected
      after FET. METHODS: This review integrates and discusses the available clinical
      and scientific evidence supporting embryo transfer in a natural cycle. RESULTS:
      Laboratory-based studies demonstrate morphological and molecular changes to the
      endometrium and reduced responsiveness of the endometrium to hCG, resulting from
      controlled ovarian stimulation. The literature demonstrates reduced endometrial
      receptivity in controlled ovarian stimulation cycles and supports the clinical
      observations that FET reduces the risk of ovarian hyperstimulation syndrome and
      improves outcomes for both the mother and baby. CONCLUSIONS: This review provides
      the basis for an evidence-based approach towards changes in routine IVF, which
      may ultimately result in higher delivery rates of healthier term babies.

PMID- 24916456
TI  - Surfactant or block copolymer micelles? Structural properties of a series of well
      defined n-alkyl-PEO micelles in water studied by SANS.
AB  - Here we present an extensive small-angle neutron scattering (SANS) structural
      characterization of micelles formed by poly(ethylene oxide)-mono-n-alkyl ethers
      (Cn-PEOx) in dilute aqueous solution. Chemically, Cn-PEOx can be considered as a
      hybrid between a low-molecular weight surfactant and an amphiphilic block
      copolymer. The present system, prepared through anionic polymerization
      techniques, is better defined than other commercially available polymers and
      allows a very precise and systematic testing of the theoretical predictions from
      thermodynamical models. The equilibrium micellar properties were elaborated by
      systematically varying the n-alkyl chain length (n) at constant PEO molecular
      weight or increasing the soluble block size (x), respectively. The structure was
      reminiscent of typical spherical star-like micelles i.e. a constant core density
      profile, ~r(0), and a diffuse corona density profile, ~r(-4/3). Through a careful
      quantitative analysis of the scattering data, it is found that the aggregation
      number, Nagg initially rapidly decreases with increasing PEO length until it
      becomes independent at higher PEO molecular weight as expected for star-like
      micelles. On the other hand, the dependency on the n-alkyl length is
      significantly stronger than that expected from the theories for star-like block
      copolymer micelles, Nagg ~ n(2) similar to what is expected for surfactant
      micelles. Hence the observed aggregation behavior suggests that the Cn-PEOx
      micelles exhibit a behavior that can be considered as a hybrid between low
      molecular weight surfactant micelles and diblock copolymer micelles. 

PMID- 24916457
TI  - Clinical and psychosocial variables associated with behavioral intentions to
      undergo surveillance endoscopy.
AB  - BACKGROUND: Many patients with Barrett's esophagus do not adhere to guideline
      recommended endoscopic surveillance. Among patient factors related to cancer
      prevention behaviors, patients' stated behavioral intention is a strong predictor
      of behavior performance. Little is known about the patient factors associated
      with having a strong behavioral intention to pursue surveillance endoscopy. This
      study explores the association of clinical and psychosocial variables and
      behavioral intention to pursue surveillance endoscopy among patients with
      Barrett's Esophagus and no or low-grade dysplasia. METHODS: Potential subjects
      were screened using electronic medical records of a regional Veterans Affairs
      Medical Center and a pathologically confirmed Barrett's esophagus registry.
      Eligible participants were recruited by a mailer or phone call and completed a
      questionnaire to measure six distinct psychosocial factors, their behavioral
      intention to undergo surveillance endoscopy, and various demographic and clinical
      variables. Univariate and multivariate linear regression identified the relation
      of behavioral intention with each of six psychosocial variables. RESULTS: One
      hundred and one subjects consented and returned surveys. The analytical sample
      for this study consists of the 94% of surveys with complete responses to the
      behavior intention items. Three of the six psychosocial domains were
      statistically significant predictors of intention in both univariate and adjusted
      univariate analysis (salience/coherence beta = 0.59, 95% CI = 0.45-0.76, P <0.01;
      self-efficacy beta = 0.30, 95% CI = 0.10-0.51, P <0.01; and social influence beta
      = 0.20, 95% CI = 0.08-0.33, P <0.01). In a multivariate analysis only
      salience/coherence (beta = 0.65, 95% CI = 0.42-0.88, P <0.01) remained
      statistically significant predictor of intention. CONCLUSION: This study
      established the validity of a scale to measure psychosocial variables associated
      with behavioral intentions to undergo surveillance endoscopy. Results demonstrate
      the importance of assessing self-efficacy, social influences, and bottom-line
      belief in the value of surveillance endoscopy when evaluating a patient's
      likelihood of completing surveillance endoscopy.

PMID- 24916458
TI  - Helping burn patients to look at their injuries: how confident are burn care
      staff and how often do they help?
AB  - Patients vary in their feelings about looking at their injuries and burn care
      staff play an important role in helping patients. This study explored confidence
      among burn care staff in helping patients to look at their injuries and how often
      help was typically offered. Burn care professionals (n=33) completed a
      questionnaire exploring confidence and practice in this area. Eighty-five percent
      (n=28) believed it was important for patients to look at their injuries but a
      significant proportion lacked confidence in preparing patients for what they
      might see (18%; n=6) and having the necessary practical skills required (24%;
      n=8). Fifty-five percent (n=18) worried about upsetting patients and 48% (n=16)
      worried about saying/doing the wrong thing. Practice varied significantly. Only
      21% (n=7) regularly (most or all of the time) informed patients where mirrors
      were situated within the ward area. Eighteen percent (n=6) of staff reported
      never or only occasionally asking patients if they had seen their injuries, 27%
      (n=9) of staff never or only occasionally asked patients if they would like to
      see their injuries and 30% (n=10) of staff never or only occasionally asked
      patients if they wanted any help looking at their injuries. Training in this area
      may be useful to enhance staff confidence so patients can be offered appropriate
      support. 

PMID- 24916459
TI  - Delays in diagnosis and treatment of pulmonary tuberculosis in Wakiso and Mukono
      districts, Uganda.
AB  - BACKGROUND: Delay in tuberculosis (TB) diagnosis may worsen the disease and
      increase TB transmission. Therefore, timely diagnosis and treatment is critical
      in TB control. We aimed to assess the treatment delay of pulmonary TB and its
      determinants in two Ugandan districts where TB infection control (TBIC)
      guidelines were formerly implemented. METHODS: A facility based cross-sectional
      study was conducted in Mukono and Wakiso districts. Adult pulmonary TB patients
      within three months of initiating treatment were included in the study. Delays
      were categorized into unacceptable patient delay (more than 3 weeks from the
      onset of cough and the first consultation with a health care provider), health
      service (more than one week from the first consultation to the initiation of TB
      treatment) and total delay (more than 4 weeks since the onset of cough). The
      prevalences as well as predictors for the three delays were determined. RESULTS:
      We enrolled 158 sputum positive patients. Unacceptable patient delay was noted in
      91 (58%) patients, a health service delay in 140 (88%) patients and a total delay
      in 140 (90%) patients. An independent predictor for patient delay was male gender
      (p < 0.001). First visiting a non-public health facility (p = 0.001) was an
      independent predictor of health service delay. CONCLUSION: There is still a
      significant TB diagnosis and treatment delay in Uganda. Most of the delay was
      caused by health system delay in the non-public health care sector. There is need
      for TB advocacy in the community, training of health workers in TBIC and
      strengthening public-private partnerships in TB control.

PMID- 24916460
TI  - Tones and numbers: a combined EEG-MEG study on the effects of musical expertise
      in magnitude comparisons of audiovisual stimuli.
AB  - This study investigated the cortical responses underlying magnitude comparisons
      of multisensory stimuli and examined the effect that musical expertise has in
      this process. The comparative judgments were based on a newly learned rule
      binding the auditory and visual stimuli within the context of magnitude
      comparisons: "the higher the pitch of the tone, the larger the number presented."
      The cortical responses were measured by simultaneous MEG?EEG recordings and a
      combined source analysis with individualized realistic head models was performed.
      Musical expertise effects were investigated by comparing musicians to non
      musicians. Congruent audiovisual stimuli, corresponding to the newly learned
      rule, elicited activity in frontotemporal and occipital areas. In contrast,
      incongruent stimuli activated temporal and parietal regions. Musicians when
      compared with nonmusicians showed increased differences between congruent and
      incongruent stimuli in a prefrontal region, thereby indicating that music
      expertise may affect multisensory comparative judgments within a generalized
      representation of analog magnitude.

PMID- 24916461
TI  - Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with
      structure-based inhibitors.
AB  - The nucleoid-associated protein HU plays an important role in maintenance of
      chromosomal architecture and in global regulation of DNA transactions in
      bacteria. Although HU is essential for growth in Mycobacterium tuberculosis
      (Mtb), there have been no reported attempts to perturb HU function with small
      molecules. Here we report the crystal structure of the N-terminal domain of HU
      from Mtb. We identify a core region within the HU-DNA interface that can be
      targeted using stilbene derivatives. These small molecules specifically inhibit
      HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene
      inhibitors induce gene expression changes in Mtb that resemble those induced by
      HU deficiency. Our results indicate that HU is a potential target for the
      development of therapies against tuberculosis. 

PMID- 24916462
TI  - Relationship between CT volumetric measurements and Doppler perfusion indices in
      gastrointestinal liver metastasis.
AB  - PURPOSE: This study investigated how the volume of hepatic metastatic lesions can
      affect liver haemodynamics and whether these perfusion parameters may help to
      differentiate benign and malignant liver lesions. MATERIALS AND METHODS: The
      Doppler perfusion index (DPI the ratio of arterial to total liver blood flow) was
      measured in 46 patients aged 29-83 years, exhibiting up to four focal hyperechoic
      liver lesions at ultrasound examination. They comprised histopathologically
      proven liver metastasis of colorectal (19 cases) and gastric (10 cases)
      adenocarcinoma without local recurrence at the site of the previously resected
      primary tumour, along with 17 subjects with haemangioma. All patients underwent
      volumetric assessment using multislice computed tomography to calculate total
      volume of hepatic lesions. RESULTS: The mean DPI of patients with colorectal (36
      +/- 2 %) and gastric (39 +/- 6 %) metastasis was significantly higher than those
      with haemangioma (14 +/- 2 %) (both p < 0.001), whereas metastatic groups did not
      exhibit any difference in terms of mean DPI. Statistically significant
      correlations were found between DPI values and calculated total volume of lesions
      in patients with colorectal and gastric metastasis (r = 0.55, p = 0.01 and r =
      0.85, p = 0.002, respectively) while this correlation was not demonstrated in the
      haemangioma group. Simple linear regression analysis revealed that every 1 cm(3)
      increment in total volume of metastatic lesions increased DPI by 0.2 % [95 %
      confidence interval (CI) 0.1-0.3, p = 0.001]. CONCLUSION: Doppler perfusion index
      alterations are directly correlated with total volume of metastatic deposits, and
      DPI measurement can be a valuable method to distinguish haemangioma from
      hyperechoic colorectal and gastric metastatic lesions.

PMID- 24916463
TI  - Extraction of chronically implanted cardiovascular electronic device leads.
AB  - OPINION STATEMENT: Cardiovascular implantable electronic devices (CIED) are a
      remarkable success story. These systems are widely used to prevent symptomatic
      bradycardia, treat malignant tachyarrhythmia, and to restore a more physiologic
      contraction to a failing left ventricle. Implantation of a CIED usually involves
      a lifelong commitment to this therapy, which, unfortunately, is not free from
      complication requiring removal and/or replacement of all or part of the system.
      The major obstacle to removal of a CIED is the fibrous attachments that develop
      between a lead and co-existent leads, veins, and the heart. This process
      increases over time such that, by one year, removal by traction alone may be
      problematic and, if aggressive, result in complication. Physicians, surgeons, and
      engineers have refined techniques of percutaneous lead extraction and developed
      tools, which have facilitated the process, increased success, and lowered the
      incidence of complication. Extraction may be performed for a variety of
      indications some of which are unanimously agreed upon while others remain
      controversial. Proponents of a broadened application of extraction have proffered
      the concept of 'lead management,' which includes the removal of all leads that
      are not clinically relevant to the patient. The benefit of this approach would be
      to limit the risk of future complication, such as venous occlusion or
      thromboembolism, and to obviate the increase in difficulty of extraction (due to
      longer implant duration) that might accompany removal should that be required in
      the future. Intuitively appealing as this approach might be, there is little
      evidence supporting it, and the extraordinarily large number of patients
      currently implanted with recalled ICD leads is indicative of the potential impact
      this practice may have. This review will discuss extraction, its indications, and
      outcomes.

PMID- 24916464
TI  - Successful aortic root replacement and shunt closure in a case with rare
      coexistence of congenital cardiac malformations: bicuspid aortic valve with
      annuloaortic ectasia, single coronary artery, and patent foramen ovale.
AB  - This is the first report of rare simultaneous complication of three cardiac
      malformations: bicuspid aortic valve with annuloaortic ectasia, single coronary
      artery, and patent foramen ovale. We successfully operated to replace the aortic
      valve and ascending aorta, and to close the patent foramen ovale. 

PMID- 24916465
TI  - Variant CJD and blood transfusion: are there additional cases?
AB  - BACKGROUND AND OBJECTIVES: In this study, we compare variant Creutzfeldt-Jakob
      disease (vCJD) cases definitely linked to blood transfusion, those with a history
      of blood transfusion in which no donor has developed vCJD and primary cases with
      no history of blood transfusion. The aim is to determine whether there are any
      differences in the demographics or clinical phenotype in these groups that might
      suggest additional cases of transfusion transmission of vCJD. MATERIALS AND
      METHODS: All cases of vCJD who are old enough to donate blood (i.e. >17 years
      old) are notified to the UKBTS at diagnosis, regardless of whether they are known
      to have a blood donation history. A search is then made for donor records and, if
      found, all components produced and issued to hospitals are identified and their
      fate determined. Recipient details are then checked against the NCJDRSU register
      to establish whether there is a match between these individuals and patients who
      have been diagnosed with vCJD. In the reverse study, attempts are made to trace
      the donors to all cases reported to have received a blood transfusion and donors'
      details are checked against the register to determine if any have developed vCJD.
      RESULTS: Of the 177 cases of vCJD diagnosed in the UK as of 1 February 2014, the
      TMER study identified 15 cases reported to have received a blood transfusion.
      Transfusion records were unavailable for 4 of these cases, all pre-1980, and in
      one other case there was no transfusion recorded in the medical notes.
      Transfusion records were found for 10 cases. One case transfused at symptom onset
      was excluded from this analysis. The mean age at onset of symptoms of the
      remaining nine transfusion recipients (four female and five male) was 42.9 years;
      57.6 years in the three known transfusion-transmitted cases and 35.5 years in the
      six not linked cases. In one of these cases, details of components transfused
      were unavailable, and the remaining five cases received a total of 116 donor
      exposures with 112 donors identified, none of whom is known to have developed
      clinical vCJD. To date, five of the 112 identified donors have died and none was
      certified as dying of vCJD or any other neurological disorder. Two of the
      transfusion-transmitted cases did not fulfil diagnostic criteria for probable
      vCJD during life but were confirmed at post-mortem. Both cases were in the older
      age range (68 and 74 years, respectively), and neither had a positive MRI brain
      scan. The remaining cases all fulfilled the criteria for the diagnosis of vCJD in
      life, but two of these had atypical features and were older than the expected age
      at onset for vCJD. CONCLUSION: In conclusion, it is possible that one or more of
      the vCJD cases that received a blood transfusion derived from an individual not
      known to have vCJD were infected by the blood transfusion. However, the evidence
      for this is weak, and the absence of a past history of transfusion in most cases
      of vCJD excludes a large number of unrecognised transfusion-transmitted cases.

PMID- 24916466
TI  - Assessment of Managed Aquifer Recharge Site Suitability Using a GIS and Modeling.
AB  - We completed a two-step regional analysis of a coastal groundwater basin to (1)
      assess regional suitability for managed aquifer recharge (MAR), and (2) quantify
      the relative impact of MAR activities on groundwater levels and sea water
      intrusion. The first step comprised an analysis of surface and subsurface
      hydrologic properties and conditions, using a geographic information system
      (GIS). Surface and subsurface data coverages were compiled, georeferenced,
      reclassified, and integrated (including novel approaches for combining related
      datasets) to derive a spatial distribution of MAR suitability values. In the
      second step, results from the GIS analysis were used with a regional groundwater
      model to assess the hydrologic impact of potential MAR placement and operating
      scenarios. For the region evaluated in this study, the Pajaro Valley Groundwater
      Basin, California, GIS results suggest that about 7% (15 km2) of the basin may be
      highly suitable for MAR. Modeling suggests that simulated MAR projects placed
      near the coast help to reduce sea water intrusion more rapidly, but these
      projects also result in increased groundwater flows to the ocean. In contrast,
      projects placed farther inland result in more long-term reduction in sea water
      intrusion and less groundwater flowing to the ocean. This work shows how combined
      GIS analysis and modeling can assist with regional water supply planning,
      including evaluation of options for enhancing groundwater resources.

PMID- 24916468
TI  - Summarizing risk using risk measures and risk indices.
AB  - Our society is fascinated with risk in many different areas and disciplines. One
      of the main ways to describe and communicate the level of risk is through risk
      indices, which summarize risk using numbers or categories such as words, letters,
      or colors. These indices are used to communicate risks to the public, understand
      how risk is changing over time, compare among different risks, and support
      decision making. Given the different methods to construct risk indices, including
      flawed methods such as risk matrices, this article develops specific steps that
      analysts can follow to create a risk index. This article emphasizes the
      importance of describing risk with a probability distribution, developing a
      numerical risk measure that summarizes the probability distribution, and finally
      translating the risk measure to an index. Measuring the risk is the most
      difficult part and requires the analyst to summarize a probability distribution
      into one or possibly a few numbers. The risk measure can then be transformed to a
      numerical or categorical index. I apply the method outlined in this article to
      construct a risk index that compares the risk of fatalities in aviation and
      highway transportation. 

PMID- 24916467
TI  - Clinical outcomes and quality of life 5 years after a randomized trial of
      concomitant or sequential phlebectomy following endovenous laser ablation for
      varicose veins.
AB  - BACKGROUND: Endovenous laser ablation (EVLA) is a popular treatment for
      superficial venous insufficiency. Debate continues regarding the optimal
      management of symptomatic varicose tributaries following ablation of the main
      saphenous trunk. This randomized trial compared the 5-year outcomes of endovenous
      laser therapy with ambulatory phlebectomy (EVLTAP) with concomitant ambulatory
      phlebectomy, and EVLA alone with sequential treatment if required following a
      delay of at least 6 weeks. METHODS: Patients undergoing EVLA for great saphenous
      vein insufficiency were randomized to receive EVLTAP or EVLA alone with
      sequential phlebectomy, if required. Outcomes included disease-specific quality
      of life (QoL) (Aberdeen Varicose Vein Questionnaire; AVVQ), requirement for
      secondary procedures, clinical severity (Venous Clinical Severity Score; VCSS),
      residual and recurrent varicose tributaries, and generic QoL. Patients were
      followed up for 5 years. RESULTS: Fifty patients were randomized equally into two
      parallel groups. The EVLTAP group had lower VCSS scores at 12 weeks (median 0
      (i.q.r. 0-1) versus 2 (0-2); P <0.001), and lower AVVQ scores at 6 weeks (median
      7.9 (i.q.r. 4.1-10.7) versus 13.5 (10.9-18.1); P < 0.001) and 12 weeks (2.0 (0.4
      7.7) versus 9.6 (2.2-13.8); P = 0.015). VCSS and AVVQ scores were equivalent by 1
      year, but only after 16 of 24 patients in the EVLA group, compared with one of 25
      in the EVLTAP group (P < 0.001), had received a secondary intervention. From 1 to
      5 years both groups had equivalent outcomes. CONCLUSION: EVLA with either
      concomitant or sequential management of tributaries is acceptable treatment for
      symptomatic varicose veins, with both treatments achieving excellent results at 5
      years. Concomitant treatment of varicosities is associated with optimal
      improvement in both clinical disease severity and QoL.

PMID- 24916469
TI  - The population genomic landscape of human genetic structure, admixture history
      and local adaptation in Peninsular Malaysia.
AB  - Peninsular Malaysia is a strategic region which might have played an important
      role in the initial peopling and subsequent human migrations in Asia. However,
      the genetic diversity and history of human populations--especially indigenous
      populations--inhabiting this area remain poorly understood. Here, we conducted a
      genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in
      four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito),
      and made comparisons of 17 world-wide populations. Our data revealed that
      Peninsular Malaysia has greater genetic diversity corresponding to its role as a
      contact zone of both early and recent human migrations in Asia. However, each
      single Orang Asli (indigenous) group was less diverse with a smaller effective
      population size (N(e)) than a European or an East Asian population, indicating a
      substantial isolation of some duration for these groups. All four MEGs were
      genetically more similar to Asian populations than to other continental groups,
      and the divergence time between MEGs and East Asian populations (12,000--6,000
      years ago) was also much shorter than that between East Asians and Europeans.
      Thus, Malaysian Orang Asli groups, despite their significantly different
      features, may share a common origin with the other Asian groups. Nevertheless, we
      identified traces of recent gene flow from non-Asians to MEGs. Finally, natural
      selection signatures were detected in a batch of genes associated with immune
      response, human height, skin pigmentation, hair and facial morphology and blood
      pressure in MEGs. Notable examples include SYN3 which is associated with human
      height in all Orang Asli groups, a height-related gene (PNPT1) and two blood
      pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long
      isolation period, subsequent gene flow and local adaptations have jointly shaped
      the genetic architectures of MEGs, and this study provides insight into the
      peopling and human migration history in Southeast Asia.

PMID- 24916471
TI  - Flow-mediated dilation is associated with endothelial oxidative stress in human
      venous endothelial cells.
AB  - Flow-mediated dilation (FMD) is recognized as a non-invasive endothelial function
      bioassay. However, FMD's relationship with endothelial cell oxidative stress in
      humans is yet to be determined. Here, we sought to determine if FMD was
      associated with endothelial nitric oxide synthase (eNOS) and endothelial
      oxidative stress in humans. Twenty-seven apparently healthy young men (26.5+/-5.9
      years) underwent brachial artery FMD testing and endothelial cell biopsy from a
      forearm vein. Non-normalized FMD (%) and three different brachial artery FMD
      normalizations were performed: (1) peak shear rate (%/SR); (2) area under the SR
      curve until peak dilation (%/AUC); and (3) AUC 30 seconds before peak dilation
      (%/AUC30). Immunofluorescence quantification was used to assess eNOS expression
      and nitrotyrosine (NT), a criterion marker of endothelial oxidative stress.
      Values for eNOS and NT expression were reported as a ratio of endothelial cell to
      human umbilical vein endothelial cell average pixel intensity. NT expression was
      significantly correlated with FMD normalized by AUC30 (r = -0.402, p<0.05). Other
      FMD normalizations and non-normalized FMD were not significantly correlated with
      NT expression (r range = -0.364 to -0.142, all p>0.05). There were no significant
      correlations between eNOS expression and normalized and non-normalized FMD (r
      range = -0.168 to -0.066, all p>0.05). In conclusion, brachial artery FMD is
      associated with venous endothelial cell oxidative stress. However, this
      association is observed only when FMD is normalized by AUC30.

PMID- 24916470
TI  - Microtubule-depolymerizing agents used in antibody-drug conjugates induce
      antitumor immunity by stimulation of dendritic cells.
AB  - Antibody-drug conjugates (ADC) are emerging as powerful treatment strategies with
      outstanding target-specificity and high therapeutic activity in patients with
      cancer. Brentuximab vedotin represents a first-in-class ADC directed against
      CD30(+) malignancies. We hypothesized that its sustained clinical responses could
      be related to the stimulation of an anticancer immune response. In this study, we
      demonstrate that the dolastatin family of microtubule inhibitors, from which the
      cytotoxic component of brentuximab vedotin is derived, comprises potent inducers
      of phenotypic and functional dendritic cell (DC) maturation. In addition to the
      direct cytotoxic effect on tumor cells, dolastatins efficiently promoted antigen
      uptake and migration of tumor-resident DCs to the tumor-draining lymph nodes.
      Exposure of murine and human DCs to dolastatins significantly increased their
      capacity to prime T cells. Underlining the requirement of an intact host immune
      system for the full therapeutic benefit of dolastatins, the antitumor effect was
      far less pronounced in immunocompromised mice. We observed substantial
      therapeutic synergies when combining dolastatins with tumor antigen-specific
      vaccination or blockade of the PD-1-PD-L1 and CTLA-4 coinhibitory pathways.
      Ultimately, treatment with ADCs using dolastatins induces DC homing and activates
      cellular antitumor immune responses in patients. Our data reveal a novel
      mechanism of action for dolastatins and provide a strong rationale for clinical
      treatment regimens combining dolastatin-based therapies, such as brentuximab
      vedotin, with immune-based therapies.

PMID- 24916473
TI  - Comparison of GDF5 and GDNF as neuroprotective factors for postnatal dopamine
      neurons in ventral mesencephalic cultures.
AB  - Loss of dopamine neurons is associated with the motor deficits that occur in
      Parkinson's disease. Although many drugs have proven to be useful in the
      treatment of the symptoms of this disease, none has been shown to have a
      significant impact on the development of the disease. However, we believe that
      several neurotrophic factors have the potential to reduce its progression. Glial
      cell line-derived neurotrophic factor (GDNF), a member of the transforming growth
      factor-beta superfamily of neurotrophic factors, has been extensively studied in
      this regard. Less attention has been paid to growth/differentiation factor 5
      (GDF5), another member of the same superfamily. This study compares GDNF and GDF5
      in dissociated cultures prepared from ventral mesencephalon and in organotypic co
      cultures containing substantia nigra, striatum, and neocortex. We report that
      both GDNF (10-500 ng/ml) and GDF5 (100-500 ng/ml) promoted the survival of
      dopamine neurons from the substantia nigra of postnatal rats, although GDNF was
      considerably more potent than GDF5. In contrast, neither factor had any
      significant effect on the survival of dopamine neurons from the rat ventral
      tegmental area. Using organotypic co-cultures, we also compared GDF5 with GDNF as
      chemoattractants for the innervation of the striatum and the neocortex by
      dopamine neurons from the substantia nigra. The addition of either GDF5 or GDNF
      (100-500 ng/ml) caused innervation by dopamine neurons into the cortex as well as
      the striatum, which did not occur in untreated cultures. Our results are
      consistent with similar findings suggesting that GDF5, like GDNF, deserves
      attention as a possible therapeutic intervention for Parkinson's disease.

PMID- 24916472
TI  - The role of HIF1alpha in renal cell carcinoma tumorigenesis.
AB  - The transcription factor HIF1alpha is implicated in the development of clear cell
      renal cell carcinoma (ccRCC). Although HIF1alpha was initially believed to be
      essential for ccRCC development, recent studies hypothesize an oncogenic role for
      HIF2alpha in ccRCC, but a tumor suppressor role for HIF1alpha, leading to
      uncertainty as to the precise roles of the different HIF transcription factors in
      this disease. Using evidence available from studies with human ccRCC cell lines,
      mouse xenografts, murine models of ccRCC, and human ccRCC specimens, we evaluate
      the roles of HIF1alpha and HIF2alpha in the pathogenesis of ccRCC. We present a
      convergence of clinical and mechanistic data supporting an important role for
      HIF1alpha in promoting tumorigenesis in a clinically important and large subset
      of ccRCC. This indicates that current understanding of the exact roles of
      HIF1alpha and HIF2alpha is incomplete and that further research is required to
      determine the diverse roles of HIF1alpha and HIF2alpha in ccRCC. KEY MESSAGES:
      The TRACK mouse ccRCC model with constitutively active HIF1alpha but not
      HIF2alpha expressed in proximal tubules develops RCC. HIF1alpha protein is
      expressed in the majority of human ccRCC specimens. Elevated HIF1alpha in ccRCC
      correlates with a worse prognosis. Many publications do not support a tumor
      suppressor role for HIF1alpha in ccRCC. HIF1alpha, but not HIF2alpha, is
      expressed in some types of cancer stem cells.

PMID- 24916474
TI  - Transanal ileoproctostomy is feasible in human cadavers.
AB  - AIM: An ileorectal bypass performed entirely through a transanal route has
      recently been described in an animal model. The present study aimed to
      demonstrate its technical feasibility in four human cadavers. METHOD: A transanal
      endoscopic microsurgery (TEM) device and endoscopic instruments were used. The
      principal steps of the procedure included insertion of the TEM device, rectostomy
      above the peritoneal reflection, peritoneoscopy using a standard gastroscope and
      delivery of the small bowel through the proctostomy to perform an anastomosis.
      RESULTS: The procedure was successfully completed using transanal access in all
      cases. The mean procedure time was 90 min. The bypass was patent, and the
      anastomosis between the intraperitoneal rectum and the terminal ileum was
      leakproof. CONCLUSION: Transanal ileoproctostomy is technically feasible in human
      cadavers. The procedure may become an alternative to stoma formation in selected
      patients with colonic obstruction.

PMID- 24916475
TI  - Nematodes infect, but do not manipulate digging by, sand crabs, Lepidopa
      benedicti.
AB  - We examined sand crabs (Lepidopa benedicti) for endoparasites, and found the only
      parasite consistently infecting the studied population were small nematodes.
      Because many nematodes have complex life cycles involving multiple hosts, often
      strongly manipulating their hosts, we hypothesized that nematodes alter the
      behavior of their sand crab hosts. We predicted that more heavily infected crabs
      would spend more time above sand than less heavily infected crabs. Our data
      indicate infection by nematodes was not correlated with duration of time crabs
      spent above sand. We also suggest that organisms living in sandy beaches may
      benefit from relatively low parasite loads due to the low diversity of species in
      the habitat. 

PMID- 24916476
TI  - Genomic studies of disease-outcome in host--pathogen dynamics.
AB  - Pathogens act as agents of evolutionary change in host populations, altering the
      host's allele frequencies and phenotypes through selection. The mechanisms
      underlying these adaptive changes depend on which defense strategy the host
      adopts upon infection. With increased anthropogenic change and loss of
      biodiversity, ecological impacts on adaptive processes may reduce the ability of
      hosts to evolve resistance, or to persist within their tolerance limits, thus
      increasing the capacity of pathogens to cause disease and mortality. In this
      review, we use amphibians and a pathogenic chytrid fungus (Batrachochytrium
      dendrobatidis, Bd) to illustrate how integrating genomic approaches into current
      research, both for hosts and pathogens, will improve our understanding of factors
      promoting the outcome of disease. As new emerging pathogens continue threatening
      amphibian populations worldwide, we recommend that researchers focus on
      individuals that survive after natural epizootics or experimental challenges.
      These survivors represent an underutilized and underexploited genetic resource
      for characterizing adaptive traits involved in the clearance of pathogens or in
      their tolerance. We highlight two target areas that will benefit from focused
      research: (1) Identification of the genetic basis of the hosts' defense
      strategies (resistance and tolerance) and of Bd's pathogenicity traits and (2)
      genomic characterization of shifts in fitness that drive seasonal and/or temporal
      patterns in host-pathogen interactions. To provide insights into hosts' survival,
      we review recent literature--including experimental Bd challenges and
      longitudinal studies--that underscore the complexity of Bd infections as
      determined by a combination of genetic and environmental factors. Given the
      heterogeneity of disease-outcomes and broad diversity of host species, amphibians
      provide a unique opportunity to identify novel genetic determinants of resistance
      to a recently emerged fungal pathogen. Developing additional genetic resources
      (e.g., genomic profiles, resistance mapping, and dual RNA-seq) will advance our
      understanding of the components of the innate and adaptive immune system acting
      on infected hosts in varying environments. These ecoimmunomic applications, which
      link host-pathogen eco-evolutionary processes with applied conservation efforts,
      will specifically benefit threatened amphibians that remain safeguarded in
      captive colonies.

PMID- 24916477
TI  - A computational fluid dynamics study on hemodynamics for different locations of
      the distal anastomosis of a bypass nearby a collateral vessel in the
      femoropopliteal area.
AB  - Revascularization of the femoropopliteal sector is often performed by the
      placement of a bypass. In this paper, we have studied the effects of hemodynamics
      on patency of the bypass for different positions of the distal anastomosis close
      to a collateral artery. Computational fluid dynamics (CFD) are used for this
      study. The cardiac cycle-averaged wall shear stress (WSS) and oscillation index
      (OSI) have been analyzed. Low WSS and high OSI may increase the risk of intimal
      hyperplasia (IH), which may reduce bypass patency. From the CFD simulations,
      spots of low WSS and high OSI are found within and near the entrance of the
      collateral artery, near the suture line, at the floor, toe, and heel. We regarded
      flow ratios of 20:80 and of 35:65. It is found that for the high flow ratio
      anastomosis located proximal to the collateral artery is clearly more
      advantageous. However for the low flow ratio anastomosis located distal to the
      collateral artery seems to be slightly more advantageous, the results are less
      conclusive. One of the studied flow geometries has been validated by in vitro
      experiments using a time resolved particle image velocimetry technique. Velocity
      fields from these experiments are in good agreement with the CFD results.

PMID- 24916478
TI  - Reasons provided for requesting a termination of pregnancy in the U.K.
AB  - OBJECTIVE: To determine the main reasons for termination of pregnancy (TOP)
      requests in a UK city. DESIGN: A survey requesting reasons for a pregnancy
      termination from women attending a TOP clinic. SETTING: A TOP pre-assessment
      clinic in Hull and East Yorkshire Hospitals, UK. POPULATION: A cohort of pregnant
      women requesting a TOP in the first trimester. METHODS: A confidential,
      anonymous, self-administered questionnaire requesting demographic information
      about age, education, ethnicity and marital status. The questionnaire also asked
      for the main reasons underlying the TOP request. The main outcome measures were
      (1) reasons for TOP requests and (2) correlations between the reasons provided
      and demographic characteristics. RESULTS: A total of 274 women participated in
      the study and 527 reasons were given. The most common reason was money worries
      (21.0%) followed closely by contraception failure (20.5%). The third most common
      reason was the anticipated effect on education or the woman's career (14.6%) Over
      half (59.5%) of the women were single and 8.8% were divorced or separated. Twenty
      eight per cent of the respondents were aged 21 years and below, 36.1% were aged
      22-29 years and 29.2% were over 30 years of age. CONCLUSIONS: The main reasons
      for TOP requests included financial constraints, contraceptive failure,
      completion of family, and potential interruption of education or career. These
      reasons differed with age groups and marital status. Focused qualitative research
      on reasons for a TOP will provide further knowledge and understanding that is
      needed to enable optimal service provision and policy planning.

PMID- 24916479
TI  - Sexually transmitted infection incidence among adolescents in Ireland.
AB  - OBJECTIVE: The burden of sexually transmitted infections (STIs) rests with young
      people, yet in Ireland there has been very little research into this population.
      The purpose of this study was to determine the incidence rate and establish risk
      factors that predict STI occurrence among adolescents in Ireland. DESIGN: Routine
      diagnostic, demographic and behavioural data from first-time visits to three
      screening centres in the southwest of Ireland were obtained. Univariate and
      multivariable logistic regression models were used to assess risk factors that
      predict STI occurrence among adolescents. RESULTS: A total of 2784 first-time
      patients, aged 13-19 years, received 3475 diagnoses between January 1999 and
      September 2009; 1168 (42%) of adolescents had notifiable STIs. The incidence rate
      of STIs is 225/100 000 person-years. Univariate analysis identified eligible risk
      factors (p<0.2) for inclusion in the multivariable model. Multivariable logistic
      regression showed the dominant risk factors for STI diagnosis to be: males who
      sometimes [odds ratio (OR) 2.02] or never (OR 1.83) use condoms; and females 18
      19 years (OR 2.26) and 16-18 years (OR 1.8), with 2 (OR 1.33) or 3+ (OR 1.56)
      partners in the last 12 months, who are non-intravenous drug users (OR 0.72), are
      most likely to receive a positive STI diagnosis. CONCLUSIONS: STI diagnosis has
      become increasingly common in Ireland. The proportion of notifications among
      those aged under 20 years is increasing. These data illustrate the significance
      of age, condom use and number of sexual partners as risk factors for STI
      diagnosis. Furthermore, providing data for the first time, we report on the high
      incidence rate of STIs among adolescents in Ireland. The high levels of risk
      taking behaviour and STI acquisition are highlighted and suggest that there is a
      need for an integrated public health approach to combat this phenomenon in the
      adolescent population.

PMID- 24916480
TI  - Propensity-matched, longitudinal outcomes analysis of complications and cost:
      comparing abdominal free flaps and implant-based breast reconstruction.
AB  - BACKGROUND: Choosing a breast reconstructive modality after mastectomy is an
      important step in the reconstructive process. The authors hypothesized that
      autologous tissue is associated with a greater success rate and cost efficacy
      over time, relative to implant reconstruction. STUDY DESIGN: A retrospective
      review was performed of patients undergoing free tissue (FF) transfer and
      expander implant (E/I) reconstruction between 2005 and 2011. Variables evaluated
      included comorbidities, surgical timing, complications, overall outcomes,
      unplanned reoperations, and costs. A propensity-matching technique was used to
      account for the nonrandomized selection of modality. RESULTS: A total of 310
      propensity-matched patients underwent 499 reconstructions. No statistically
      significant differences in preoperative variables were noted between propensity
      matched cohorts. Operative characteristics were similar between FF and E/I
      reconstructions. The E/I reconstruction was associated with a significantly
      higher rate of reconstructive failure (5.6% vs 1.2%, p < 0.001). Expander implant
      reconstructions were associated with higher rates of seroma (p = 0.009) and lower
      rates of medical complications (p = 0.02), but overall significantly higher rates
      of unplanned operations (15.5% vs 5.8%, p = 0.002). The total cost of
      reconstruction did not differ significantly between groups ($23,120.49 +/-
      $6,969.56 vs $22,739.91 +/- $9,727.79, p = 0.060), but E/I reconstruction was
      associated with higher total cost for secondary procedures ($10,157.89 +/-
      $8,741.77 vs $3,200.71 +/- $4,780.64, p < 0.0001) and a higher cost of unplanned
      revisions over time (p < 0.05). CONCLUSIONS: Our matched outcomes analysis does
      demonstrate a higher overall, 2-year success rate using FF reconstruction and a
      significantly lower rate of unplanned surgical revisions and cost. Although
      autologous reconstruction is not ideal for every patient, these findings can be
      used to enhance preoperative discussions when choosing a reconstructive modality.

PMID- 24916481
TI  - Discordant indigenous and provider frames explain challenges in improving access
      to arthritis care: a qualitative study using constructivist grounded theory.
AB  - INTRODUCTION: Access to health services is a determinant of population health and
      is known to be reduced for a variety of specialist services for Indigenous
      populations in Canada. With arthritis being the most common chronic condition
      experienced by Indigenous populations and causing high levels of disability, it
      is critical to resolve access disparities through an understanding of barriers
      and facilitators to care. The objective of this study was to inform future health
      services reform by investigating health care access from the perspective of
      Aboriginal people with arthritis and health professionals. METHODS: Using
      constructivist grounded theory methodology we investigated Indigenous peoples'
      experiences in accessing arthritis care through the reports of 16 patients and 15
      healthcare providers in Alberta, Canada. Semi-structured interviews were
      conducted between July 2012 and February 2013 and transcribed verbatim. The
      patient and provider data were first analyzed separately by two team members then
      brought together to form a framework. The framework was refined through further
      analysis following the multidisciplinary research team's discussions. Once the
      framework was developed, reports on the patient and provider data were shared
      with each participant group independently and participants were interviewed to
      assess validity of the summary. RESULTS: In the resulting theoretical framework
      Indigenous participants framed their experience with arthritis as 'toughing it
      out' and spoke of racism encountered in the healthcare setting as a deterrent to
      pursuing care. Healthcare providers were frustrated by high disease severity and
      missed appointments, and framed Indigenous patients as lacking 'buy-in'.
      Constraints imposed by complex healthcare systems contributed to tensions between
      Indigenous peoples and providers. CONCLUSION: Low specialist care utilization
      rates among Indigenous people cannot be attributed to cultural and social
      preferences. Further, the assumptions made by providers lead to stereotyping and
      racism and reinforce rejection of healthcare by patients. Examples of 'working
      around' the system were revealed and showed potential for improved utilization of
      specialist services. This framework has significant implications for health
      policy and indicates that culturally safe services are a priority in addressing
      chronic disease management.

PMID- 24916482
TI  - Acute respiratory distress syndrome (ARDS) treated successfully by veno-venous
      extracorporeal membrane oxygenation (ECMO) in a nearly drowned patient.
AB  - This report highlights about one acute respiratory distress syndrome (ARDS) case
      after near-drowning resuscitated using extracorporeal membrane oxygenation
      (ECMO). Few cases have been reported about ECMO use for near-drowning and in most
      of these cases, ECMO was initiated within the first week. However, in our report,
      we would like to emphasize that seemingly irreversible secondary worsening of
      ARDS after nearly drowned patient was successfully treated by ECMO use more than
      1 week after near-drowning followed by discharge without home oxygen therapy,
      social support, or any complication. This is probably due to sufficient lung rest
      for ventilator-associated lung injury during ECMO use. Based on our case's
      clinical course, intensive care unit physicians must consider ECMO even in the
      late phase of worsened ARDS after near-drowning. 

PMID- 24916484
TI  - NO adsorption and reaction on single crystal rutile TiO2(110) surfaces studied
      using UHV-FTIRS.
AB  - The adsorption and reaction of NO on both the oxidized and reduced single crystal
      rutile TiO2(110) surfaces were studied in a UHV-FTIRS system at low temperature.
      The monodentate adsorption configuration of the cis-(NO)2 dimer at bridge oxygen
      vacancy (Vo) sites was detected for the first time on reduced TiO2(110) surfaces.
      With the aid of (NO)2 dimer adsorption anisotropy, the bidentate configuration of
      the cis-(NO)2 dimer on fivefold coordinated Ti5c(4+) cation sites was clearly
      confirmed. The (NO)2 dimer converts to N2O on Ti5c(4+) cation sites at higher NO
      dosage on both oxidized and reduced surfaces, rather than at Vo sites. The (NO)2 
      > N2O conversion is independent of the presence of Vo on TiO2(110) surfaces. To
      explain the signs of absorption bands of the dimer monodentate configuration, the
      local optical constant at Vo sites was introduced. 

PMID- 24916483
TI  - The EUPHRATES trial (Evaluating the Use of Polymyxin B Hemoperfusion in a
      Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock):
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Septic shock is common and has unacceptably high morbidity,
      mortality, and associated cost with numerous failed attempts at developing
      effective therapies. Endotoxin, one of the most potent mediators of sepsis, is
      found in high levels in approximately 50% of patients with septic shock.
      Polymyxin B (PMX) hemoperfusion has been shown in numerous studies to
      successfully remove endotoxin and potentially improve outcomes. EUPHRATES
      (Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial
      of Adults Treated for Endotoxemia and Septic shock) is a theragnostic trial
      (matching blood measurement to treatment capability) of PMX hemoperfusion in
      patients with septic shock and confirmed endotoxemia as measured by the endotoxin
      activity assay (EAA). METHODS: EUPHRATES is a pivotal regulatory trial that is
      multi-centered, placebo-controlled and blinded. The trial is being conducted in
      fifty ICUs in the United States and Canada and is powered to enroll 360 patients.
      Patients with persistent septic shock despite adequate fluid resuscitation on
      vasopressors for more than 2 and less than 30 hours are eligible for measurement
      of the EAA. Those with EAA >=0.60 are eligible to be randomized to treatment with
      two sessions of PMX hemoperfusion 24 hours apart. The primary endpoint for the
      trial is 28-day all-cause mortality. DISCUSSION: Unique features of the trial
      include absence of systemic inflammatory response (SIRS) criteria as a
      requirement for inclusion, use of the EAA to confirm endotoxemia as a requisite
      for treatment, and use of a detailed "facade" hemoperfusion event as a blinding
      mechanism. The outcomes of the second interim analysis included a resizing of the
      trial to 650 patients and the addition of an exclusion criterion of subjects with
      multiple organ dysfunction score (MODS) <= 9. Results are anticipated in 2016.
      TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01046669. Registered:
      January 8, 2010.

PMID- 24916485
TI  - Veterans Affairs Saint Louis University Mental Status examination compared with
      the Montreal Cognitive Assessment and the Short Test of Mental Status.
AB  - OBJECTIVES: To compare the ability of the Veterans Affairs Saint Louis University
      Mental Status (SLUMS) examination to detect mild cognitive impairment (MCI) and
      dementia according to the Clinical Dementia Rating Scale (CDR) with that of two
      other well-known screening instruments, the Montreal Cognitive Assessment (MoCA)
      and the Short Test of Mental Status (STMS). DESIGN: Cross-sectional validation
      study. SETTING: Saint Louis Veterans Affairs Medical Center Geriatric Research
      Education and Clinical Center. PARTICIPANTS: Veterans aged 60 and older (median
      78.5) with a high school education or more (n = 136). MEASUREMENTS: Participants
      were administered the SLUMS examination, the MoCA, and the STMS in random order.
      A blinded test administrator administered the CDR in a separate session. Receiver
      operating characteristic (ROC) curves were used to assess the sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of the SLUMS examination, the MoCA, and the STMS for MCI, dementia, and MCI or
      dementia. ROC contrasts were used to statistically compare the area under the ROC
      curve (AUC) for the screening tests' ability to detect cognitive dysfunction
      according to the CDR. RESULTS: ROC contrasts demonstrated that the AUCs for
      detecting MCI (SLUMS examination 0.74, MoCA 0.77, STMS 0.77), dementia (SLUMS
      examination 0.98, MoCA 0.96, STMS 0.97), and MCI or dementia (SLUMS examination
      0.82, MoCA 0.83, STMS 0.84) were equivalent. Sensitivity, specificity, PPV, and
      NPV were similar across measures of MCI, dementia, and MCI or dementia according
      to the CDR. CONCLUSION: The SLUMS examination has validity similar to that of the
      MoCA and STMS for the detection of MCI, dementia, and MCI or dementia according
      to the CDR.

PMID- 24916486
TI  - Reductions in reported deaths following the introduction of extended-release
      oxycodone (OxyContin) with an abuse-deterrent formulation.
AB  - PURPOSE: Abuse of opioid analgesics for their psychoactive effects is associated
      with a large number of fatalities. The effect of making opioid tablets harder to
      crush/dissolve on opioid-related fatalities has not been assessed. The objective
      of this study was to assess the impact of introducing extended-release oxycodone
      (ERO [OxyContin((r)) ]) tablets containing physicochemical barriers to
      crushing/dissolving (reformulated ERO) on deaths reported to the manufacturer.
      METHODS: All spontaneous adverse event reports of death in the US reported to the
      manufacturer between 3Q2009 and 3Q2013 involving ERO were used. The mean numbers
      of deaths/quarter in the 3 years after reformulated ERO introduction were
      compared with the year before. Changes in the slope of trends in deaths were
      assessed using spline regression. Comparison groups consisted of non-fatal
      reports involving ERO and fatality reports involving ER morphine. RESULTS:
      Reports of death decreased 82% (95% CI: -89, -73) from the year before to the
      third year after (131 to 23 deaths per year) reformulation; overdose death
      reports decreased 87% (95% CI: -93, -78) and overdose deaths with mention of
      abuse-related behavior decreased 86% (95% CI:-92, -75). In contrast, non-fatal
      ERO reports did not decrease post-reformulation, and reported ER morphine
      fatalities remained unchanged. The ratio of ERO fatalities to all oxycodone
      fatalities decreased from 21% to 8% in the year pre-reformulation to the second
      year post-reformulation. CONCLUSIONS: These findings, when considered in the
      context of previously published studies using other surveillance systems, suggest
      that the abuse-deterrent characteristics of reformulated ERO have decreased the
      fatalities associated with its misuse/abuse. (c) 2014 The Authors.
      Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

PMID- 24916487
TI  - Effect of acute hyperglycemia on moderately hypothermic GL261 mouse glioma
      monitored by T1-weighted DCE MRI.
AB  - OBJECTIVE: We sought to evaluate the effects of acute hyperglycemia induced by
      intraperitoneal injection of glucose (2.7 g/kg) on vascular delivery to GL261
      mouse gliomas kept at moderate hypothermia (~30  degrees C). MATERIALS AND
      METHODS: Seven GL261 glioma-bearing mice were studied by T1-weighted DCE MRI
      before and after an injection of glucose (n = 4) or saline (n = 3). Maximum
      relative contrast enhancement (RCE) and initial area under the enhancement curve
      (IAUC) were determined in each pixel. RESULTS: The mean tumor parameter values
      showed no significant changes after injecting either saline (RCE -5.9 +/- 5.0 %;
      IAUC -3.7 +/- 3.6 %) or glucose (RCE -1.6 +/- 9.0 %; IAUC +0.6 +/- 6.4 %). Pixel
      by-pixel analysis revealed small post-injection changes in RCE and IAUC between
      the glucose and saline groups, all within 13 % range of their baseline values.
      CONCLUSION: Perturbing the metabolism of GL261 tumors kept at moderate
      hypothermia with hyperglycemia did not induce significant changes in the
      permeability/perfusion of these tumors. This is relevant for future studies with
      this model since regional differences in glucose accumulation could thus reflect
      basal heterogeneities in vasculature and/or metabolism of GL261 tumors.

PMID- 24916489
TI  - Editorial.

PMID- 24916488
TI  - Simulation study on a stationary data acquisition SPECT system with multi-pinhole
      collimators attached to a triple-head gamma camera system.
AB  - OBJECTIVES: The aim of the study was to develop a new SPECT system that makes it
      possible to acquire projection data stationary using a triple-head gamma camera
      system. METHODS: We evaluated several data acquisition geometry with multi
      pinhole collimators attached to a triple-head gamma camera system. The number of
      pinholes for each camera was three to twelve, and we located these holes on
      collimator plates adequately. These collimator holes were tilted by predefined
      angles to efficiently cover the field of view of the data acquisition system.
      Acquired data were reconstructed with the OS-EM method. In the simulations, we
      used a three-dimensional point source phantom, brain phantom, and myocardial
      phantom. Attenuation correction was conducted with the x-ray CT image of the
      corresponding slice. RESULTS: Reconstructed images of the point source phantom
      showed that the spatial resolution could be improved with the small number of
      pinholes. On the other hand, reconstructed images of the brain phantom showed
      that the large number of pinholes yielded images with less artifact. The results
      of the simulations with the myocardial phantom showed that more than eight
      pinholes could yield an accurate distribution of activity when the source was
      distributed only in the myocardium. CONCLUSIONS: The results of the simulations
      confirmed that more than eight pinholes for each detector were required to
      reconstruct an artifact free image in the triple-head SPECT system for imaging of
      brain and myocardium.

PMID- 24916490
TI  - Treatment of depressive symptoms and attitudes towards treatment options in a
      representative German general population sample.
AB  - Objective. To estimate treatment rates, self-medication, and preferences for
      treatment options of depressive symptoms. Methods. A German nationwide
      representative sample (n=2224) was interviewed. Subjects were asked to fill in a
      depressive symptom checklist, as well as to answer questions about current
      treatments and treatment preferences. Results. A total of 16.7% was mildly, 7.5%
      moderately and 6.5% strongly affected by depressive symptoms; 22.7% of the total
      affected group were currently or previously being treated by a physician. Self
      initiated treatments had been stated as effective in 54.2% of cases. The
      preference for phytotherapeutic treatment approaches was about 3-6-fold higher
      than for standard antidepressants and psychotherapies. Treatment preference and
      wish for treatment increased with increasing severity of symptoms with regard to
      treatments that had to be professionally initiated. Conclusion. Despite
      considerable educational efforts, the prevalence of untreated and undiagnosed
      depressive symptoms seems to be high. There is still little acceptance for the
      most efficacious therapies for depression. More efforts should be made to
      increase knowledge about self-administered phytotherapeutic drugs, which might
      play an important role in a stepped-care approach of future depression
      management. 

PMID- 24916491
TI  - Revised psychopharmacological algorithms for the treatment of mood disorders in
      Japan.
AB  - Objective. To revise the psychopharmacology algorithms for the treatment of mood
      disorders published in 1999 in Japan. Methods. The algorithms were established
      based on clinical psychopharmacological evidence, the results of a questionnaire
      survey sent to 200 Japanese psychiatrists, and the consensus of all the research
      members. Results. Six categorized algorithms have been developed, i.e. mild or
      moderate major depression, severe non-psychotic major depression, psychotic
      depression, mania, bipolar depression, and rapid cycling mood disorder.
      Conclusion. The revised algorithms will be helpful for the treatment of mood
      disorders in Japan. 

PMID- 24916492
TI  - Mood and anxiety disorders in patients with multiple sclerosis.
AB  - Objective. This study aims to investigate the current prevalences of mood and
      anxiety disorders, as well as the sociodemographic and clinical features
      associated with these disorders in multiple sclerosis (MS). Method. A total of 74
      patients with relapsing-remitting MS (42 patients in exacerbation phase, 32
      patients in remission phase) were included in the study. Mood and anxiety
      disorders were diagnosed by means of the Structured Clinical Interview for DSM-IV
      (SCID-I). The Expanded Disability Status Scale (EDSS) was used to determine
      degree of disability due to MS. Results. Forty-five (60.8%) patients met the
      criterion of at least one mood or anxiety disorder. Major depression (33.8%) was
      the most common psychiatric diagnosis. Generalized anxiety disorder (18.9%),
      specific phobia (18.9%) and obsessive-compulsive disorder (OCD) (14.9%) were
      other frequent psychiatric disorders. Major depression, panic disorder and OCD
      were significantly more common among patients in the exacerbation phase compared
      to patients in the remission phase. The predictors of any depressive disorder
      were presence of exacerbation phase of MS and higher disability level, and the
      predictors of any anxiety disorder were presence of exacerbation phase of MS and
      shorter disease duration. Conclusions. Our results suggest that the patients with
      relapsing-remitting MS, particularly during exacerbation phase have high
      prevalence of mood and anxiety disorders. 

PMID- 24916493
TI  - A survey of psychiatrists' attitudes to schizoaffective disorder.
AB  - Objective. Schizoaffective disorder is an established diagnosis in both ICD-10
      and DSM-IV, but research evidence relating to its nosological status and
      aetiology is conflicting. This study aimed to examine the attitudes of practising
      consultant psychiatrists, and to see whether there is a consensus about its
      classification and value in everyday clinical psychiatry. Method. A questionnaire
      was mailed to 2000 consultant psychiatrists drawn randomly from the membership
      list of the Royal College of Psychiatrists in the United Kingdom. Respondents
      were asked to rate their level of agreement with a series of statements about
      schizoaffective disorder and give some basic demographic data. Results. Of over
      800 respondents, almost all reported using the diagnosis in clinical practice,
      but a small minority reported that they never use the diagnosis. Most
      psychiatrists considered the diagnosis to be clinically useful but there was
      little agreement about its nature, its relationship to other mental illnesses,
      its aetiology, or its characteristic clinical features. Conclusions.
      Schizoaffective disorder is an established diagnosis in psychiatric practice and
      is valued by clinicians but there is little consensus of opinion or practice in
      relation to it. Psychiatrists should be careful to use the diagnosis in
      accordance with current classificatory schemes, and further research should
      continue to investigate both its conceptual validity and its use in clinical
      practice. 

PMID- 24916494
TI  - Co-prescription of antidepressants with other psychotropics: Distinct profile of
      escitalopram.
AB  - Objective. Recent meta-analyses have argued that there are no clinically
      significant differences between various selective serotonin reuptake inhibitors
      (SSRIs) or between SSRIs and other antidepressants. Analysis of large-scale
      national prescription databases may offer a unique opportunity to see whether
      this premise holds true in actual practice. National databases however, should be
      viewed with caution as they reveal only limited information about efficacy and
      tolerability. Methods. The number of antidepressants prescribed annually (October
      2004 to September 2005), as well as the class of drug and the use of any
      additional psychotropics were obtained from the Israeli subsidiary of
      Intercontinental Marketing Services (IMS) Health. Results. During the 12-month
      study period there were 2,107,763 prescriptions of antidepressants reported by
      IMS in Israel. Compared to other drug classes, the SSRIs were used significantly
      more often as a sole therapy (chi-square=1343, df=3, P<0.0001). Of the SSRIs,
      escitalopram was the most frequently prescribed (79%) as monotherapy, followed by
      fluoxetine with 72% and <70% for the other SSRIs. The most frequently prescribed
      additional psychotropic was a benzodiazepine, in the range of 38 to nearly 50%.
      Conclusion. Antidepressants vary significantly in their use as a single
      ("monotherapy") drug. The use of additional psychotropics could reflect either
      the presence of symptoms not well covered by a particular antidepressant or for
      addressing side effects particular to a certain class of antidepressants.The
      premise that all SSRIs are equal is not reflected in this current examination. 

PMID- 24916495
TI  - Insight in first-episode schizophrenia.
AB  - Objective. To compare insight impairment, including its temporal changes, between
      remitters and nonremitters in patients with first-episode schizophrenia. Method.
      Males, consecutively hospitalized with diagnosed first-episode schizophrenia
      (according to ICD 10), who provided written informed consent, and were reassessed
      at the 1-year follow-up were included. The psychopathology was evaluated using
      the Positive and Negative Syndrome Scale (PANSS) prior to acute treatment - on
      admission; at the end of the acute treatment - at discharge; at the 1-year follow
      up. Insight was measured using item G12 from the PANSS. Results. Ninety-three
      patients (mean age 23 years, mean duration of illness 0.77 years) were reassessed
      after 1 year. A total of 73/93 patients (78%) fulfilled the criteria for
      remission. When compared, remitters and nonremitters showed no significant
      difference in impaired judgement and insight on admission. The mean value of this
      item was significantly lower at discharge even in nonremitters; however, a
      significantly higher value was found after 1 year in nonremitters. In remitters
      the impaired insight decreased significantly at discharge and there was a
      significant additional decrease after 1 year. In nonremitters there was a
      significant decrease at discharge; however, a significant increase was observed
      after 1 year. In the 73 remitters the rate of insight impairment was 79.4% on
      admission, 46.6% at discharge and 10.9% after 1 year; the same values were 90, 20
      and 70% in the 20 nonremitters. In both remitters and nonremitters the lack of
      judgement and insight was the first or second most frequently observed item at
      all three time points. The impaired insight on admission was strongly associated
      with the overall symptomatology, including positive, negative and general
      psychopathology on admission in both remitters and nonremitters. Only in
      remitters was the impaired insight at discharge associated with symptoms at
      discharge, on admission and also after 1 year. The impaired insight at the 1-year
      follow-up was associated with some symptoms after 1 year in both remitters and
      nonremitters. Conclusion. Insight may be state dependent, especially in patients
      with a good outcome. Attitudes towards treatment and insight into the illness may
      vary during the course of the illness. However, more longitudinal prospective
      studies are needed to verify such state-related change, and the factors that may
      underlie the acquisition of insight. 

PMID- 24916496
TI  - Sense of coherence in patients after limb amputation and in patients after spine
      surgery.
AB  - Objective. To assess the score of SOC (sense of coherence), BDI (Beck Depression
      Scale), STAI ( State and Trait Anxiety Inventory) in three examined groups and
      correlation of SOC score with sociodemographic data, anxiety and depression.
      Methods. The SOC, BDI, STAI questionnaires were given to 51 patients after limb
      amputation, 65 patients after vertebral surgery because of chronic back pain and
      40 persons in the control group. Results. Patients after limb amputation achieved
      the same level of SOC score as the control group. Patients who had higher results
      on the SOC score rarely suffered from phantom pain. Patients after spine surgery
      had a lower level on the SOC score than the control group. A lower score of SOC
      was observed in older, unemployed, poorer educated, subjects taking medicine, who
      did not report improvement after operation. Patients after limb amputation and
      patients after spinal surgery were more depressed and anxious than healthy
      people. Conclusion. Patients with higher SOC results, in both examined groups,
      were less depressed and anxious. 

PMID- 24916497
TI  - Can we predict short-term side effects of methylphenidate immediate-release?
AB  - Objective. In children and adolescents who were prescribed immediate-release
      methylphenidate (MPH-IR) for the first time, we aimed to investigate the effect
      of gender, psychiatric co-morbidity and the baseline severity of clinical
      symptoms on the short-term side-effects of the medication. Method. In a clinical
      sample, over a period of 6 months, all MPH-naive patients with attention deficit
      hyperactivity disorder (ADHD) (N=90; male, n=73; female, n=17) age: 9.0+/-2.2
      years (5-16 years)) were included. Patients were prescribed MPH-IR 10-30 mg/day
      (17.6+/-4.95). The assessment included structured measurements, including the
      Turgay Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM
      IV)-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T
      DSM-IV-S) (parents and teachers), Conners' Teacher Rating Scale for ADHD-Short
      version (teachers). Parents also completed the "Barkley Stimulants' Side Effects
      Rating Scale" (BSSERS) at baseline and on the third, seventh and 15th days of
      medication. Results. Repeated measures multiple ANOVA revealed an overall
      significant difference in BSSERS between the baseline measures and the 15th day
      (P<0.01). On the 15th day, only the "loss of appetite" item severity scores
      increased (P=0.001), whereas the scores of "irritability", "proneness to cry",
      "anxiety", "nail biting" and "euphoria" items decreased significantly. In post
      hoc analyses, when subjects whose side effects increased and did not increase
      were compared, chi-square tests revealed a significant difference (P=0.029) only
      for the presence of co-morbidity, and no difference for the gender, age, dosage
      of MPH, and the baseline severity of inattentiveness and/or hyperactivity.
      Discussion. The only significant increase during MPH treatment was for the "loss
      of appetite" item on BSSERS. Our results suggest that some of the BSSERS items
      may represent both the ADHD symptoms and the side effects. When overall BSSERS
      item severity is considered, having a co-morbid diagnosis may be predictive of
      more severe adverse effects. 

PMID- 24916498
TI  - NETER 1 alcoholic 5 subtypes: Validity with Lesch four evolutionary subtypes.
AB  - Objective. To validate NAT (NETER's alcoholic typology), taking into account the
      differentiated distribution of the measures used as external criteria in alcohol
      dependent sub-groups and its relationship with Lesch's alcoholic typology (LAT).
      Method. A sample of 133 alcohol-dependent patients integrated in the alcoholism
      unit of the Psychiatric Service of Santa Maria University Hospital were included
      in the study. Results and Conclusions. Convergent validity was assured by the
      agreement between the subtypes of the two typologies (NAT and Lesch), considering
      the same underlying model of alcoholism development: anxiopathic subtype of NAT
      and Type II (model of anxiety, alcohol as conflict solution) of Lesch and the
      tymopathic subtype of NAT and type III (model of depression, alcohol as
      antidepressant) of Lesch. Discriminant analysis (external criteria) showed
      significant differences between the subtypes in the following variables: gender;
      tobacco; beer and whisky consumption; daily average of drinks; clinical
      conditions such as delirium tremens, alcoholic blackouts and seizures; severity
      of alcohol-related problems; psychological dimensions such as psychological
      maturity and extroversion; and suicidal ideation during the alcohol consumption
      period. A more exhaustive description of alcoholic sub-groups may improve genetic
      studies of alcoholism and provide the alcoholic patient with an adequate specific
      therapeutic protocol. 

PMID- 24916499
TI  - Real-world use of quetiapine in early psychosis: An acute inpatient and community
      follow-up effectiveness study.
AB  - Objective. To evaluate the use of quetiapine in first episode psychosis in
      adolescents and adults in a 26-week open-label trial. Methods. Consenting
      patients were recruited from consecutive acute psychiatric admissions. Quetiapine
      was increased stepwise to 750 mg. Baseline, 2, 4, 12, 16, 20 and 26 week
      measurement included: BPRS, PANSS, CGI, and indices of tolerability and safety.
      Change was assessed using repeated measures ANOVA. Results. Of 73 first admission
      patients with psychosis, 15 entered the study. Loss of otherwise eligible
      patients was mainly related to prospective consent, which appeared to cause
      selection bias. All 15 patients were retained for 4-week Intention-to-Treat
      Analysis; nine completed the 26-week protocol (Completers Analysis). Non
      completers dropped out shortly after 4 weeks. In the ITT Analysis, there was
      significant improvement on BPRS Total (P<0.01), PANSS Positive (P<0.05), and CGI
      (P<0.01) scores. No change in the 2-week BPRS Total score predicted subsequent
      non-response to quetiapine. In the Completers Analysis, onset of significant
      PANSS Negative score reduction did not occur until week 12. By 26 weeks all
      efficacy measures had substantially improved; and substance abuse was markedly
      less prevalent (P=0.02). Adverse events included postural hypotension,
      drowsiness, and significant weight gain (P=0.001). CONCLUSIONS: This uncontrolled
      trial suggests quetiapine is an effective first-line treatment in young early
      psychosis patients. Prospective consent is a major barrier to evaluating acute
      care for psychotic disorder.

PMID- 24916500
TI  - Risperidone long-acting injectable for maintenance therapy in bipolar disorder:
      An open-label pilot study.
AB  - Objective. To investigate the maintained efficacy of antipsychotic therapy in
      stable patients with bipolar disorder transitioned directly to risperidone long
      acting injectable (RLAI). Methods. Within a large multi-centre European trial
      (StoRMi), adults with bipolar I disorder (DSM-IV) stable on a medication regimen
      for >=1 month, but requiring a change of antipsychotic therapy, received
      injections of RLAI 25mg i.m. (increased to 37.5 or 50 mg if necessary), every 14
      days for 6 months. Results. Sixteen patients were included in this subgroup
      analysis. Reasons for changing to RLAI included non-compliance (eight patients),
      insufficient efficacy (four patients) and side effects (three patients),
      associated with previous therapy. Twelve patients completed the 6-month trial.
      The most common dosage at endpoint was 25mg (seven patients). Disease symptoms
      (CGI Disease Severity) were significantly reduced from baseline to endpoint
      (P=0.0225). Patient satisfaction with treatment increased from baseline to
      endpoint, with 36% of patients rating their treatment satisfaction as "very good"
      versus 0% at baseline. Mean total score of ESRS improved from baseline to
      endpoint. Conclusion. Patients with bipolar disorder showed maintained symptom
      control over a 6-month treatment period with RLAI. Controlled studies in this
      population are required. 

PMID- 24916501
TI  - Admission rates of patients with borderline personality disorder in a psychiatric
      unit in a General Hospital.
AB  - This study examined the admission rates of patients with borderline personality
      disorder in a psychiatric unit within a General Hospital. The medical records of
      patients with DSM-IV borderline personality disorder who were admitted to the
      unit during the years 2004 and 2005 were retrospectively reviewed. The number of
      admissions of patients with borderline personality disorder was 78, involving 48
      patients. The mean of admissions were 1.63 per patient. The comparison to the
      rest of the patient population (922 patients with a total of 1086 admissions)
      demonstrated that patients with borderline personality disorder were admitted
      more frequently than patients with major psychiatric disorders. The difference
      was statistically significant (P=0.042). The main reasons for admission were
      suicide attempts or threats and lack of out-patient facilities. The introduction
      of out-patient psychiatric facilities may contribute to the reduction of the
      admissions and to the better management of the disorder. 

PMID- 24916502
TI  - Validity of the Beck Depression Inventory in the postpartum period.
AB  - Objective. While there is a recommendation to screen for postpartum depression
      (PPD), there are worries about the validity of instruments other than the
      Edinburgh Postnatal Depression Scale; little is known about the construct
      validity of one of the most used screening instruments, the Beck Depression
      Inventory, in this period. Methods. This study evaluated the validity and
      reliability of the BDI in a population-based sample of women and their spouses
      (n=772) in the postpartum. Additionally, we compared factor scores within the
      couple. Results. Exploratory factor analysis demonstrated a two-factor solution
      (depressive symptoms and somatic symptoms), accounting for 44.01% of the total
      variance. Internal consistency was good (Cronbach's alpha=0.90). Women had higher
      scores than their partners in both factors (P<0.001), but not a higher proportion
      of the total score attributable to somatic symptoms. Conclusion. With little
      factor variance between women and men, and a similar proportion of somatic
      symptoms, these results should be taken to reinforce the validity of the BDI in
      the postpartum. 

PMID- 24916503
TI  - Still no evidence that benzodiazepines cause depression.
AB  - A large number of drugs have been implicated in causing depression by case
      reports and case series. For a few specific drugs, the association has
      subsequently been confirmed by appropriately designed studies. In other
      instances, a lack of substantiating evidence has lead to a gradual disappearance
      of concern about a potential association. The benzodiazepines represent a
      deviation from this pattern: they are widely believed to cause depression, but
      there is a lack of evidence to substantiate this claim. In DSM-IV, there is a
      category of mood disorder for drug-induced depression (substance-induced mood
      disorder), and the text of the manual specifically refers to benzodiazepines as a
      potential cause. Despite the apparently entrenched nature of this belief, there
      continues to be a lack of credible evidence that benzodiazepines can cause
      depression as a side effect. 

PMID- 24916505
TI  - Elevated cerebral lactate: Implications in the pathogenesis of hepatic
      encephalopathy.
AB  - Hepatic encephalopathy (HE), a complex neuropsychiatric syndrome, is a frequent
      complication of liver failure/disease. Increased concentrations of lactate are
      commonly observed in HE patients, in the systemic circulation, but also in the
      brain. Traditionally, increased cerebral lactate is considered a marker of energy
      failure/impairment however alterations in lactate homeostasis may also lead to a
      rise in brain lactate and result in neuronal dysfunction. The latter may involve
      the development of brain edema. This review will target the significance of
      increased cerebral lactate in the pathogenesis of HE. 

PMID- 24916506
TI  - PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia.
AB  - Addition of rituximab (R) to fludarabine and cyclophosphamide (FC) has
      significantly improved patient outcomes in chronic lymphocytic leukemia (CLL).
      Whether baseline gene expression can identify patients who will benefit from
      immunochemotherapy over chemotherapy alone has not been determined. We assessed
      genome-wide expression of 300 pretreatment specimens from a subset of 552
      patients in REACH, a study of FC or R-FC in relapsed CLL. An independent test set
      was derived from 282 pretreatment specimens from CLL8, a study of FC or R-FC in
      treatment-naive patients. Genes specific for benefit from R-FC were determined by
      assessing treatment-gene interactions in Cox proportional hazards models. REACH
      patients with higher pretreatment protein tyrosine kinase 2 (PTK2) messenger RNA
      levels derived greater benefit from R-FC, with significant improvements in
      progression-free survival, independent of known prognostic factors in a
      multivariate model. Examination of PTK2 gene expression in CLL8 patients yielded
      similar results. Furthermore, PTK2 inhibition blunted R-dependent cell death in
      vitro. This retrospective analysis from 2 independent trials revealed that
      increased PTK2 expression is associated with improved outcomes for CLL patients
      treated with R-FC vs FC. PTK2 expression may be a useful biomarker for patient
      selection in future trials. These trials were registered at
      www.clinicaltrials.gov as #NCT00090051 (REACH) and #NCT00281918 (CLL8). 

PMID- 24916504
TI  - Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue
      transcriptomics and venom proteomics.
AB  - BACKGROUND: Animal venoms attract enormous interest given their potential for
      pharmacological discovery and understanding the evolution of natural chemistries.
      Next-generation transcriptomics and proteomics provide unparalleled, but
      underexploited, capabilities for venom characterization. We combined multi-tissue
      RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom
      gland specific transcripts and venom proteins from the Western black widow spider
      (Latrodectus hesperus) and investigated their evolution. RESULTS: We estimated
      expression of 97,217 L. hesperus transcripts in venom glands relative to silk and
      cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs),
      many of which BLAST and GO term analyses indicate may function as toxins or their
      delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor
      cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of
      VSTs had predicted protein domains. Latrotoxins are venom toxins that cause
      massive neurotransmitter release from vertebrate or invertebrate neurons. We
      discovered >= 20 divergent latrotoxin paralogs expressed in L. hesperus venom
      glands, significantly increasing this biomedically important family. Mass
      spectrometry of L. hesperus venom identified 49 proteins from VSTs, 24 of which
      BLAST to toxins. Phylogenetic analyses showed venom gland specific gene family
      expansions and shifts in tissue expression. CONCLUSIONS: Quantitative expression
      analyses comparing multiple tissues are necessary to identify venom gland
      specific transcripts. We present a black widow venom specific exome that uncovers
      a trove of diverse toxins and associated proteins, suggesting a dynamic
      evolutionary history. This justifies a reevaluation of the functional activities
      of black widow venom in light of its emerging complexity.

PMID- 24916508
TI  - Who is the best donor for a related HLA haplotype-mismatched transplant?
AB  - The best donor for a related donor for a human leukocyte antigen (HLA) haplotype
      mismatched transplant for hematological neoplasms is controversial. We studied
      outcomes in 1210 consecutive transplant recipients treated on a uniform protocol.
      Younger donors and male donors were associated with less nonrelapse mortality
      (NRM; hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.01-0.39; P =
      .008 and HR = 0.65; 95% CI = 0.49-0.85; P = .002) and better survival (HR = 0.73;
      95% CI = 0.54-0.97; P = .033 and HR = 0.73; 95% CI = 0.59-0.91; P = .005). Father
      donors were associated with less NRM (HR = 0.65; 95% CI = 0.45-0.95; P = .02),
      acute graft-versus-host disease (GVHD) (HR = 0.69; 95% CI = 0.55-0.86; P = .001),
      and better survival (HR = 0.66; 95% CI = 0.50-0.87; P = .003) compared with
      mother donors. Children donors were associated with less acute GVHD than sibling
      donors (HR = 0.57; 95% CI = 0.31-0.91; P = .01). Older sister donors were
      inferior to father donors with regard to NRM (HR = 1.87; 95% CI = 1.10-3.20; P =
      .02) and survival (HR = 1.59; 95% CI = 1.05-2.40; P = .03). Noninherited maternal
      antigen-mismatched sibling donors were associated with the lowest incidence of
      acute GVHD compared with parental donors and noninherited paternal antigen
      mismatched sibling donors. Specific HLA disparities were not significantly
      correlated with transplant outcomes. Our data indicate which HLA haplotype
      mismatched related donors are associated with the best transplant outcomes in
      persons with hematological neoplasms. 

PMID- 24916507
TI  - Heme-bound iron activates placenta growth factor in erythroid cells via erythroid
      Kruppel-like factor.
AB  - In adults with sickle cell disease (SCD), markers of iron burden are associated
      with excessive production of the angiogenic protein placenta growth factor (PlGF)
      and high estimated pulmonary artery pressure. Enforced PlGF expression in mice
      stimulates production of the potent vasoconstrictor endothelin-1, producing
      pulmonary hypertension. We now demonstrate heme-bound iron (hemin) induces PlGF
      mRNA >200-fold in a dose- and time-dependent fashion. In murine and human
      erythroid cells, expression of erythroid Kruppel-like factor (EKLF) precedes
      PlGF, and its enforced expression in human erythroid progenitor cells induces
      PlGF mRNA. Hemin-induced expression of PlGF is abolished in EKLF-deficient murine
      erythroid cells but rescued by conditional expression of EKLF. Chromatin
      immunoprecipitation reveals that EKLF binds to the PlGF promoter region. SCD
      patients show higher level expression of both EKLF and PlGF mRNA in circulating
      blood cells, and markers of iron overload are associated with high PlGF and early
      mortality. Finally, PlGF association with iron burden generalizes to other human
      diseases of iron overload. Our results demonstrate a specific mechanistic pathway
      induced by excess iron that is linked in humans with SCD and in mice to markers
      of vasculopathy and pulmonary hypertension. These trials were registered at
      www.clinicaltrials.gov as #NCT00007150, #NCT00023296, #NCT00081523, and
      #NCT00352430. 

PMID- 24916509
TI  - Synergistic defects of different molecules in the cytotoxic pathway lead to
      clinical familial hemophagocytic lymphohistiocytosis.
AB  - Several molecules (LYST, AP3, RAB27A, STX11, STXBP2, MUNC13-4, and PRF1) have
      been associated with the function of cytotoxic lymphocytes. Biallelic defects in
      all of these molecules have been associated with familial hemophagocytic
      lymphohistiocytosis (FHL). We retrospectively reviewed the genetic and immunology
      test results from 2701 patients with a clinically suspected diagnosis of
      hemophagocytic lymphohistiocytosis and found 28 patients with single heterozygous
      mutations in 2 FHL-associated genes. Of these patients, 21 had mutations within
      PRF1 and a degranulation gene, and 7 were found to have mutations within 2 genes
      involved in the degranulation pathway. In patients with combination defects
      involving 2 genes in the degranulation pathway, CD107a degranulation was
      decreased, comparable to patients with biallelic mutations in one of the genes in
      the degranulation pathway. This suggests a potential digenic mode of inheritance
      of FHL as a result of a synergistic function effect within genes involved in
      cytotoxic lymphocyte degranulation. 

PMID- 24916510
TI  - Banerjee P, Tripp A, Lairmore MD, Crawford L, Sieburg M, Ramos JC, Harrington W
      Jr, Beilke MA, Feuer G. Adult T-cell leukemia/lymphoma development in HTLV-1
      infected humanized SCID mice. Blood. 2010;115(13):2640-2648.

PMID- 24916511
TI  - Effects of a preventive parenting intervention for divorced families on the
      intergenerational transmission of parenting attitudes in young adult offspring.
AB  - This study evaluates whether the New Beginnings Program (NBP), a parenting
      intervention for divorced mothers, led to positive parenting attitudes in young
      adult offspring. Data were collected from 240 mothers (G1) and offspring (G2) at
      ages 9-12 and again in adolescence and young adulthood. Alternative theoretical
      models were tested to examine mediators of NBP effects on G2 parenting attitudes.
      Significant interactions between condition and baseline G1 parenting indicated
      that NBP improved G2's parenting attitudes for those exposed to poorer G1
      parenting at program entry. Effects on G2 warm attitudes were partially mediated
      through program effects on G1 warm parenting. The implications of improving
      parenting attitudes in offspring who experience parental divorce on well-being in
      the next generation are discussed. 

PMID- 24916512
TI  - Biophysical characterization of the type III secretion tip proteins and the tip
      proteins attached to bacterium-like particles.
AB  - Bacterium-like particles (BLPs), derived from Lactococcus lactis, offer a self
      adjuvanting delivery vehicle for subunit protein vaccines. Proteins can be
      specifically loaded onto the BLPs via a peptidoglycan anchoring (PA) domain. In
      this study, the tip proteins IpaD, SipD, and LcrV belonging to type III secretion
      systems of Shigella flexneri, Salmonella enterica, and Yersinia enterocolitica,
      respectively, were fused to the PA and loaded onto the BLPs. Herein, we
      biophysically characterized these nine samples and condensed the spectroscopic
      results into three-index empirical phase diagrams (EPDs). The EPDs show
      distinctions between the IpaD/SipD and LcrV subfamilies of tip proteins, based on
      their physical stability, even upon addition of the PA. Upon attachment to the
      BLPs, the BLPs become defining moiety in the spectroscopic measurements, leaving
      the tip proteins to have a subtle yet modulating effect on the structural
      integrity of the tip proteins-BLPs binding. In summary, this work provides a
      comprehensive view of physical stability of the tip proteins and tip protein-BLPs
      and serves as a baseline for screening of excipients to increase the stability of
      the tip protein-BLPs for future vaccine formulation.

PMID- 24916514
TI  - Carbon dioxide monitoring during laparoscopic-assisted bariatric surgery in
      severely obese patients: transcutaneous versus end-tidal techniques.
AB  - Various factors including severe obesity or increases in intra-abdominal pressure
      during laparoscopy can lead to inaccuracies in end-tidal carbon dioxide (PETCO2)
      monitoring. The current study prospectively compares ET and transcutaneous (TC)
      CO2 monitoring in severely obese adolescents and young adults during laparoscopic
      assisted bariatric surgery. Carbon dioxide was measured with both ET and TC
      devices during insufflation and laparoscopic bariatric surgery. The differences
      between each measure (PETCO2 and TC-CO2) and the PaCO2 were compared using a non
      paired t test, Fisher's exact test, and a Bland-Altman analysis. The study cohort
      included 25 adolescents with a mean body mass index of 50.2 kg/m2 undergoing
      laparoscopic bariatric surgery. There was no difference in the absolute
      difference between the TC-CO2 and PaCO2 (3.2+/-3.0 mmHg) and the absolute
      difference between the PETCO2 and PaCO2 (3.7+/-2.5 mmHg). The bias and precision
      were 0.3 and 4.3 mmHg for TC monitoring versus PaCO2 and 3.2 and 3.2 mmHg for ET
      monitoring versus PaCO2. In the young severely obese population both TC and
      PETCO2 monitoring can be used to effectively estimate PaCO2. The correlation of
      PaCO2 to TC-CO2 is good, and similar to the correlation of PaCO2 to PETCO2. In
      this population, both of these non-invasive measures of PaCO2 can be used to
      monitor ventilation and minimize arterial blood gas sampling.

PMID- 24916515
TI  - Repeated early hemofiltration filters clotting and heparin-induced
      thrombocytopenia in ICU.
AB  - Repeated early hemofiltration filter clotting are real thrombotic events.
      Diagnosis of heparin-induced thrombocytopenia (HIT) in this setting in ICU
      remains difficult. We describe two cases of repeated early hemofiltration filters
      clotting in ICU and to evaluate their impact on the probability test 4T's score
      and diagnosis of HIT. Two patients undergoing at least three repeated early
      hemofiltration clotting filters in <6 h revealing HIT in ICU had a low
      probability score for HIT. Despite a 4T's score of three for the two patients and
      persistent early hemofiltration clotting filters, functional tests for HIT
      antibodies (heparin induced platelet activation assay and serotonin release
      assay) were positive, permitting the diagnosis of HIT in both patients. We
      suggest that the occurrence of repeated, rapid (within 6 h) hemofiltration filter
      clotting should score as two points for "Thrombosis" in the 4T's scoring system,
      thereby increasing the pretest probability for HIT in this clinical situation. 

PMID- 24916516
TI  - Do we need readjustment of the biochemical parameters in first trimester combined
      aneuploidy screening test in women with polycystic ovary syndrome?
AB  - OBJECTIVE: The aim of this study was to determine whether polycystic ovary
      syndrome (PCOS) affects the biochemical components of first trimester combined
      aneuploidy screening test. METHOD: A case-control study was performed at a
      tertiary referral hospital between years 2007-2013. Singleton pregnancies in the
      first trimester (11(+0) -13(+6) week) who had a history of PCOS and underwent
      first trimester combined aneuploidy screening test were included in the study.
      Three hundred and seventeen women met the criteria for inclusion. Control group
      was formed by 942 healthy pregnant women with similar gestational and maternal
      ages using a 1 : 3 ratio. Pregnancy-associated plasma protein-A (PAPP-A), free
      beta-human chorionic gonadotropin (fbeta-hCG) and fetal nuchal translucency were
      compared between the study group and the controls. RESULTS: The biochemical
      components PAPP-A and fbeta-hCG were significantly lower in the PCOS group
      compared with the control group (p = 0.001). There was no difference among groups
      with regard to the nuchal translucency measurements (p = 0.128). CONCLUSION: Our
      study shows that the levels of biochemical components of first trimester combined
      aneuploidy screening test (PAPP-A and fbeta-hCG) are altered in pregnant women
      with PCOS. Future trials of larger scale are needed to asses any need for
      readjustment of the risk in the patient population with PCOS.

PMID- 24916517
TI  - Overdiagnosis of gastro-esophageal reflux disease and underdiagnosis of
      functional dyspepsia in a USA community.
AB  - BACKGROUND: There is symptom overlap between gastro-esophageal reflux disease
      (GERD) and functional dyspepsia (FD). We aimed to test the hypothesis that FD
      cases are now more likely mislabeled as GERD. METHODS: In subjects from Olmsted
      County, MN seen at Mayo Clinic: (i) Investigation of GERD and FD diagnosis rates
      between 1985 and 2009. (ii) Assessment of survey-based upper gastrointestinal
      symptoms between 1988 and 2009. (iii) Analysis of patients reporting GERD and/or
      FD symptoms and subsequently receiving a consistent diagnosis of GERD and/or FD
      during a medical encounter. (iv) Assess the association between PPI use and GERD
      and/or FD symptoms and between actual diagnoses received. KEY RESULTS: (i) Yearly
      GERD diagnosis rates rose between 1985 and 2009 (325-1866 per 100 000). FD
      diagnosis rates rose from 45 in 1985, to 964 in 1999 but decreased to 452 per 100
      000 in 2009. (ii) Reported GERD symptoms did not significantly change between
      three survey waves in the years 1988-2009 (p = 0.052), whereas FD symptoms
      slightly increased (p = 0.01). (iii) 62.9% of subjects reporting GERD symptoms
      received a GERD diagnosis, however only 12.5% of subjects reporting FD symptoms
      received a FD diagnosis. (iv) PPI use was associated with documented GERD
      diagnosis (p < 0.001), however there was no significant association between GERD
      symptoms and PPI use (p = 0.078). CONCLUSIONS & INFERENCES: We have found
      evidence supporting a systematic bias away from diagnosing FD, favoring a GERD
      diagnosis.

PMID- 24916518
TI  - The Fc gamma receptor IIa R131H polymorphism is associated with inhibitor
      development in severe hemophilia A.
AB  - BACKGROUND: The development of factor (F) VIII neutralizing alloantibodies
      (inhibitors) is a major complication of treatment with FVIII concentrates in
      hemophilia A and the etiology is still poorly understood. The low-affinity Fc
      gamma receptors (FcgammaR), which are expressed on immune cells, provide an
      important link between cellular and humoral immunity by interacting with IgG
      subtypes. Genetic variations of the genes encoding FcgammaRs (FCGR genes) have
      been associated with susceptibility to infectious and autoimmune diseases.
      OBJECTIVES: The aim of this study was to investigate the association between
      genetic variation of FCGR and inhibitor development in severe hemophilia A.
      PATIENTS/METHODS: In this case-control study samples of 85 severe hemophilia A
      patients (siblings from 44 families) were included. Single nucleotide
      polymorphisms and copy number variation of the FCGR2 and FCGR3 gene cluster were
      studied in an FCGR-specific multiplex ligation-dependent probe amplification
      assay. Frequencies were compared in a generalized estimating equation regression
      model. RESULTS: Thirty-six patients (42%) had a positive history of inhibitor
      development. The polymorphism 131R > H in the FCGR2A gene was associated with an
      increased risk of inhibitor development (odds ratio [OR] per H-allele, 1.8; 95%
      confidence interval [CI], 1.1-2.9). This association persisted in 29 patients
      with high titer inhibitors (OR per H-allele, 1.9; 95% CI, 1.2-3.2) and in 44
      patients with the F8 intron 22 inversion (OR per H-allele, 2.6; 95% CI, 1.1-6.6).
      CONCLUSIONS: Hemophilia A patients with the HH genotype of the FCGR2A
      polymorphism 131R > H have a more than 3-fold increased risk of inhibitor
      development compared with patients with the RR genotype.

PMID- 24916519
TI  - Dynamics of intact immunoglobulin G explored by drift-tube ion-mobility mass
      spectrometry and molecular modeling.
AB  - Collision cross-sections (CCS) of immunoglobulins G1 and G4 have been determined
      using linear drift-tube ion-mobility mass spectrometry. Intact antibodies and Fc
      hinge fragments present with a larger range of CCS than proteins of comparable
      size. This is rationalized with MD simulations, which indicate significant in
      vacuo dynamics between linked folded domains. The IgG4 subclass presents over a
      wider CCS range than the IgG1 subclass. 

PMID- 24916520
TI  - Oxytocin makes females, but not males, less forgiving following betrayal of
      trust.
AB  - Although oxytocin has been shown to enhance trust behavior, to date no study has
      directly established whether oxytocin can modulate the effect of repair
      strategies on restoring damaged trust. In the current double-blind, between
      subjects, placebo-controlled design study, two repair strategies were used to
      examine the effect of intranasal oxytocin administration on modulating trust
      restoration in a revised trust game. The results showed that although oxytocin
      had no overall effect on modulating trust restoration, it did have a significant
      gender specific effect. Female subjects showed less evidence for trust repair in
      the oxytocin compared with the placebo treatment group. This suggests that
      oxytocin may make female subjects exhibit more punitive behavior towards partners
      who violate their trust and less sensitive to repair strategies provided by them.
      Interestingly, this gender specific effect was more evident in the context of
      attempted trust repair using financial compensation. However, it also extended to
      both apology alone and no compensation conditions, but not to the fair one, in
      females exhibiting high trait forgiveness. Thus females with a more forgiving
      attitude towards betrayal may actually be more likely to punish betrayal
      following oxytocin treatment. 

PMID- 24916521
TI  - Knowledge and prevalence of viral hepatitis among beauticians.
AB  - Beauty treatments, such as tattooing, piercing, manicures, pedicures, and
      barbershop shaving, can pose an important risk of virus transmission. This study
      was conducted to determine hepatitis A virus (HAV), hepatitis B virus (HBV), and
      hepatitis C virus (HCV) prevalence in a sample of beauticians from Rio de Janeiro
      (Southeast Brazil) and to assess the knowledge and attitudes of these
      professionals regarding viral hepatitis and their practices during their
      activities. One hundred nineteen beauticians were recruited in September 2010.
      Serum samples were tested for total anti-HAV, total anti-HBc, HBsAg, anti-HBs,
      and anti-HCV reactivity. A questionnaire was administered to identify socio
      demographic risk factors and to determine knowledge and attitudes regarding viral
      hepatitis. Prevalence was 73.9% for total anti-HAV, 0% for HBsAg, 5.9% for anti
      HBc, 23.6% for anti-HBs, and 0.8% for anti-HCV. Most professionals (81.5%) were
      well informed (4-7 correct answers) and reported the use of disposable sandpaper
      and nail sticks and sterilized pliers, but only 40% of them reported adequate
      processes of disinfection/sterilization. In conclusion, a high prevalence of HAV
      infection and a low prevalence of HBV and HCV infection were observed among
      beauticians. In addition, most of these individuals were not immune to HBV,
      indicating the need for vaccination campaigns targeting these professionals. Most
      of these professionals were well informed regarding viral hepatitis, although
      there was a gap in knowledge regarding disinfection and sterilization procedures.
      Public health prevention strategies should be adopted to improve education about
      disinfection/sterilization procedures for manicures and pedicures.

PMID- 24916522
TI  - Tehran lipid and glucose study: a legacy for prospective community-based
      research.

PMID- 24916523
TI  - Reference values for serum creatinine with Jaffe-compensated assay in adult
      Iranian subjects: Tehran Lipid and Glucose Study.
AB  - BACKGROUND: Chronic kidney disease is a worldwide public health problem and
      glomerular filtration rate (GFR), the best overall index of renal function, is
      most commonly estimated from serum creatinine concentrations. The aim of this
      study was to determine reference values for serum creatinine concentrations using
      data from a population-based study in Iran. METHODS: Serum creatinine was
      measured using the Jaffe method in 5247 men and women, aged 20-88 years,
      participants of the Tehran Lipid and Glucose Study. For calculating Jaffe
      compensated creatinine values in 382 samples, serum creatinine was measured using
      both the Jaffe and the enzymatic p-aminophenazone (PAP) methods. Linear
      regression analysis yielded a regression line equation of Jaffe-creatinine=0.863
      * PAP-creatinine + 38.9 MUmol/L (r = 0.973, n = 382, P < 0.001). CLSI/IFCC
      guidelines (International Federation of Clinical Chemistry/ Clinical and
      Laboratory Standards Institute), non-parametric method was used for determining
      creatinine reference values. RESULTS: Reference values for serum creatinine
      ranged between 47-98 MUmol/L (0.53-1.11 mg/dL), 37-68 MUmol/L (0.42-0.77 mg/dL),
      and 37-78 MUmol/L (0.42-0.88 mg/dL) in men, non-menopausal women, and menopausal
      women, respectively. Mean serum creatinine concentration was significantly higher
      in men compared to women for both age <= 50 years [70 +/- 11 vs. 50 +/- 10
      MUmol/L (0.79 +/- 0.12 vs. 0.57 +/- 0.11 mg/dL), P < 0.001] and age > 50 years
      [73 +/- 12 vs. 55 +/- 12 MUmol/L (0.83 +/- 0.14 vs. 0.62 +/- 0.14 mg/dL), P <
      0.001]. CONCLUSION: Reference values for serum creatinine using the compensated
      Jaffe method are presented in Iranian subjects, values that could help assessment
      of kidney function.

PMID- 24916524
TI  - Body mass index as a measure of percentage body fat prediction and excess
      adiposity diagnosis among Iranian adolescents.
AB  - BACKGROUND: Although various anthropometric methods are available for assessing
      body composition, these have not been compared in Iranian adolescents. The
      objective of the present study was to compare body mass index (BMI), waist
      circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR) and
      sum of four skinfolds as predictors of percentage body fat (PBF) and diagnosis of
      excess adiposity in Iranian adolescents. METHODS: In this cross-sectional study,
      all anthropometric measurements were made in133 adolescents (65 boys and 68
      girls), aged 10-18 years.PBF was determined using the bioelectrical impedance
      analysis method. Linear regression and receiver operating characteristic (ROC)
      analysis were used to analyze the data. Potential covariates including sex, age,
      and pubertal stage were adjusted. RESULTS: R(2)adj of models for BMI, WC, WHR,
      WHtR, and skinfolds were 0.67, 0.56, 0.19, 0.56, and 0.56, respectively (P <
      0.001). The AUC value of BMI to differentiate between normal and obese
      adolescents was 0.92 (P < 0.001). The AUC of BMI was significantly higher than
      those of WC, WHR, and WHtR (P < 0.05). CONCLUSIONS: The performance of BMI is
      better than other anthropometric indices in predicting PBF and diagnosing excess
      adiposity in Iranian adolescents.

PMID- 24916525
TI  - Secular trend of menopausal age and related factors among Tehrani women born from
      1930 to 1960; Tehran Lipid and Glucose Study.
AB  - BACKGROUND: Menopause is an important milestone of a woman's reproductive life.
      There is limited data on the secular trend of menopausal age. The purpose of this
      study is to identify the secular trend of menopausal age and its related factors
      among Tehrani women born during 1930 - 1960. METHODS: A total number of 2266
      women, born between 1930 and 1960, were recruited among TLGS participants. The
      World Health Organization classification was used to define menopause status.
      Birth cohorts were created using 10-year periods, and statistical comparisons
      were performed with analysis of covariance (ANCOVA). RESULTS: The means for
      menopausal age of women born in the 1930s, 1940s and 1950s were 48.5, 49.5 and
      49.9 years, respectively. After adjustment for possible confounding factors in
      the linear regression model, the increasing trend of menopausal age was constant
      (P = 0.029). CONCLUSION: There is an increasing trend in menopausal age in female
      residents of Tehran. These findings have implications for endogenous lifetime
      exposure of women to gonadal steroids.

PMID- 24916526
TI  - Recurrence risk ratio of siblings and familial aggregation of the metabolic
      syndrome among Tehranian population.
AB  - BACKGROUND: In this study, we aimed to determine the extent of possible genetic
      influence on cardio-metabolic risk factors, evaluate the familial aggregation of
      MetS and estimate the siblings' recurrence risk ratios in a Tehrani population.
      METHODS: In a cross-sectional observational study, we made anthropometric, blood
      pressure, and biochemical measurements in each member of 566 Tehrani nuclear
      families. RESULTS: Grandmothers had the highest incidence of atherosclerotic risk
      factors. Four factors were found which accounted for 77.7% of the overall
      variance. Recurrence risk ratio among siblings was 5.61 (95% confidence interval
      [CI]: 3.15-9.97). The adjusted odds ratio (OR) of proband's MetS status was 1.33
      (95% CI: 1.06-1.67). The adjusted OR for the four factors to predict MetS were
      all significant, with obesity having the highest risk (OR: 7.50, CI: 5.91-9.52),
      followed by dyslipidemia/hyperglycemia (OR: 4.86, CI: 4.03-5.87), and blood
      pressure (OR: 4.20, CI: 3.51-5.02). CONCLUSION: A high risk of MetS (five-fold)
      was found in siblings with MetS proband. Moreover, findings confirm the
      importance of obesity for the aggregation of MetS by nearly seven-fold in the
      study population.

PMID- 24916527
TI  - Low carbohydrate diet score does not predict metabolic syndrome in children and
      adolescents: Tehran Lipid and Glucose Study.
AB  - BACKGROUND: The aim of the study was to evaluate the ability of a low
      carbohydrate diet score (LCD) to predict the occurrence of the metabolic syndrome
      (MetS) and its components in a group of Tehrani children and adolescents after
      3.6 years of follow-up. METHODS: Diet scores were calculated using a validated
      semi-quantitative food frequency questionnaire for participants aged 6-19 years,
      selected from the Tehran Lipid and Glucose Study cohort. The LCD was calculated
      based on intake of carbohydrate, monounsaturated fatty acids, refined grains and
      vegetable protein intake, expressed as a percentage of energy as well as fiber,
      n3/n6 polyunsaturated fatty acids and glycemic load. The higher the score, the
      more closely the participant's diet followed the pattern of LCD. The incidence of
      MetS and its components was calculated three years later. RESULTS: The mean age
      of the participants was 13.8 +/- 3.6 years and 45.4% were boys. The incidence
      rates of MetS, high blood pressure, high triglycerides, low HDL-C, abdominal
      obesity, and high blood glucose were 7.5%, 11%, 15%, 6.9%, 18.3%, and 12.3%,
      respectively. Compared to those in the lowest quartile of LCD score, after
      adjusting for age, sex, physical activity, and energy intake, participants in the
      highest quartile of LCD score had odds ratios of 0.74 (95% CI: 0.24-2.28), 1.16
      (95% CI: 0.47-2.81), 0.55(95% CI: 0.21-1.44), 0.49 (95% CI: 0.11-2.08), 0.91 (95%
      CI: 0.42-1.98), and 1.28 (95% CI: 0.51-3.20) with the incidence of MetS, high
      blood pressure, high triglycerides, low HDL-C, abdominal obesity, and high blood
      glucose. CONCLUSION: No association was found between LCD and the incidence of
      MetS or its components in children and adolescents in Tehran after 3.6 years of
      follow up.

PMID- 24916528
TI  - Metabolic syndrome and health-related quality of life in reproductive age and
      post-menopausal women: Tehran Lipid and Glucose Study.
AB  - BACKGROUND: Given the lack of data clarifying the manner in which women with
      metabolic syndrome (MetS) in different eras of their life perceive their health
      related quality of life (HRQoL), this study aimed at investigating the
      association between MetS and HRQoL in reproductive age and post menopausal women.
      METHODS: This was a cross-sectional study conducted within the framework of
      Tehran Lipid and Glucose Study (TLGS). Metabolic syndrome was defined according
      to the Joint Interim Statement (JIS) and HRQoL was assessed using the Short Form
      Health Survey (SF-36). Logistic regression analysis was used to estimate the odds
      ratio (OR) of poor HRQoL with 95% confidence intervals (CIs) for reproductive age
      and post-menopausal women separately and adjusted for confounding variables.
      RESULTS: All 603 participants with (n = 340) and without (n = 263) MetS were
      studied. Overall, in both physical and mental domains, those without MetS had
      higher scores in all subscales of SF-36 except for vitality, role emotional and
      mental component summary. Unadjusted odds ratios (95% CI) for poor physical HRQoL
      were 2.8 (1.7-4.6); (P < 0.001) and 1.5 (0.7-3.4) for the reproductive age and
      post-menopausal groups, respectively. Compared to the post-menopausal group, the
      odds ratio of reporting poor HRQoL for reproductive age women was significantly
      higher, even after adjusting for age (OR: 1.7, 95% CI: 1.0-3.0, P < 0.05).
      CONCLUSION: The results indicate that MetS is associated with poor HRQoL in
      reproductive age, but not in post-menopausal women, and the association is
      observed mainly in relation to physical rather than mental health.

PMID- 24916529
TI  - Hyperglycemia in VLBW infants; incidence, risk factors and outcome.
AB  - BACKGROUND: Neonatal hyperglycemia, which is relatively common in very low birth
      weight (VLBW) infants, is associated with increased risk of morbidity and
      mortality. OBJECTIVE: To study the incidence of neonatal hyperglycemia,
      associated risk factors and the outcome of it in VLBW infants hospitalized in a
      level III NICU in Tehran. METHODS: All VLBW newborns admitted to the NICU of
      Mahdieh Hospital from April 2009 to March 2011 were considered eligible for this
      retrospective study. All relevant prenatal and perinatal data, as well as details
      of the hospital stay until discharge or death, were extracted from the case notes
      and analyzed. RESULTS: Hyperglycemia (blood suger above 150 mg/dL) was observed
      in 179 (31.7%) of the 564 VLBW infants included in the study; 48 infants (26.8%),
      had received insulin. Risk factors included: low gestational age, (OR = 4.07, 95%
      CI = 2.09-7.93, P < 0.001), extremely low birth weight (ELBW) , (OR = 5.97, 95%
      CI = 3.77-9.44, P < 0.001), dopamine administration (OR = 2.19, 95% CI = 1.32
      3.65, P = 0.003), intralipid (OR = 1.52, 95% CI = 1.04-2.22, P = 0.03), Low APGAR
      score at 5 minutes (OR = 4.44, 95% CI = 2.48-7.94, P < 0.001), RDS and its
      complications (OR = 4.20, 95% CI = 2.55-6.93, P < 0.001), were independently
      associated with hyperglycemia. Other findings with hyperglycemia were: high
      incidence of IVH >grade II (OR = 2.88, 95% CI = 1.28-6.49, P = 0.01), hospital
      stay more than 28 days in survivors,(OR = 3.56, 95% CI = 2.02-6.25, P < 0.001),
      mortality (OR = 4.42, 95% CI = 3.00-6.52, P < 0.001) and more retinopathy of
      prematurity (ROP >= stage II) in survivors (OR = 2.05, 95% CI = 1.11-3.78, P =
      0.02). CONCLUSION: Neonatal hyperglycemia developed in approximately one-third of
      our VLBW neonates. Relative prevalence and associated findings underscore the
      need for preventive measures and prompt management.

PMID- 24916530
TI  - White rice consumption is a risk factor for metabolic syndrome in Tehrani adults:
      a prospective approach in Tehran Lipid and Glucose Study.
AB  - BACKGROUND: Consumption of white rice has been proposed as a dietary risk factor
      for development of metabolic disorders and type 2 diabetes, especially in
      populations who consume white rice as a staple food. In this study, we
      investigated the association between consumption of white rice and the occurrence
      of metabolic syndrome in Tehrani adults after 3 years of follow-up. METHODS: This
      longitudinal study was conducted within the framework of the Tehran Lipid and
      Glucose Study on 1476 adults, aged 19-70 years. Dietary intakes were measured
      using a validated semi-quantitative food frequency questionnaire at baseline.
      Biochemical and anthropometric measurements were assessed and documented at
      baseline (2006-2008) and again 3 years later (2009-2011). Multiple logistic
      regression models were used to estimate the occurrence of the MetS in each
      quartile of white rice consumption. RESULTS: The mean age of participants was
      37.8 +/- 12.3 years, and mean BMI was 26.0 +/- 4.5 Kg/m2 at baseline.
      Participants in the highest quartile of white rice consumption were significantly
      younger, had lower HDL-C levels, and higher systolic and diastolic blood
      pressures at baseline (P < 0.01). Higher consumption of white rice was also
      accompanied by higher increase in serum triglyceride levels after the 3-year
      follow-up (9.9 +/- 2.3 vs. 8.2 +/- 2.3%, P < 0.01). After adjustment for all
      potential confounders, the risk of metabolic syndrome in the highest quartile of
      white rice consumption compared with the lowest, was 1.66 (95% CI: 1.04-2.66).
      Moreover, participants with central obesity, low physical activity or low-fiber
      diet had greater risk of metabolic syndrome if white rice constituted >=25.6% of
      total energy. CONCLUSION: We demonstrated that higher consumption of white rice
      may be a risk factor for development of metabolic syndrome among Iranian adults.

PMID- 24916531
TI  - Seasonal variations of blood pressure in adults: Tehran lipid and glucose study.
AB  - There is no comprehensive report on seasonal variations in individuals' blood
      pressure (BP) in Iranian subjects. The aim of this study is to evaluate
      individuals' BP during the four seasons of the year in a large number of adults
      in Tehran. In a population-based study in Tehran, over a period of ten years
      (from 1998 to 2011) during the follow up of the four phases of the TLGS, data
      from a total of 29777 participants aged 20-80 years (42.29% male and 57.71%
      female) were collected. The participants' systolic and diastolic BP (SBP and DBP)
      were measured in every season, and adjusted for weight, age, sex, body mass
      index, and ambient temperature, history of diabetes mellitus and anti
      hypertensive drugs, and their mean SBPs and DBPs were compared. Mean SBP and DBP
      was 116.79 and 75.29 in spring, 116.11 and 74.81 in summer, 117.45 and 75.95 in
      fall and 119.03 and 76.28 mmHg in winter. There was a statistically significant
      difference between mean SBP in summer and winter (P < 0.010). The difference
      between mean SBP in winter and spring and the difference of mean DBP in winter
      and summer were near significance level (P = 0.058 and 0.086, respectively).
      Compared to summer and spring, the individuals' SBP was higher during winter and
      their DBP in winter was also higher compared to summer. More attention should be
      paid to BP measurement in epidemiological studies.

PMID- 24916532
TI  - Genes associated with low serum high-density lipoprotein cholesterol.
AB  - Atherosclerosis is the main cause of death in the world through causing ischemic
      heart disease (IHD). Altered serum lipid level is the most important risk factor
      for coronary artery disease (CAD). Many studies reveal a strong inverse
      association between low levels of high density lipoprotein cholesterol (HDL-C)
      and increased risk of IHD. On the other hand, plasma levels of HDL-C has a strong
      hereditary basis. This review focuses on recent data about genetic defects that
      reduce the level of HDL-C. In order to investigate possible genes linked to low
      HDL-C disorder, we reviewed previous studies; we searched current medical
      literature from September 1990 through January 2013 for the genetics causes of
      low HDL-C levels. Genetic defects in ATP binding cassette protein (ABCA1),
      apolipoprotein (APO) A1, lecithin cholesteryl acyl transferase, Lipoprotein
      lipase (LPL), and angiopoietin-like 3 proteins (ANGPTL3) associated with low HDL
      C. Other potentially important candidates involved in low HDL-C syndromes are
      metabolic disorders including sphingomyelin phosphodiesterase 1 and
      glucocerebrosidase. Also Molecular variations in many genes such as ABCAI and
      APOAI, TRIB1 and Apo E, lipoprotein lipase (LPL), WW domain-containing
      oxidoreductase (WWOX), Hepatic lipase (HL), lecithin cholesteryl acyl transferase
      and some linkage analysis have been associated with reduced HDL-Status. Low HDL-C
      syndrome has a strong genetic basis and is correlated with an increased risk of
      CAD.

PMID- 24916533
TI  - Multiple endocrine neoplasia type IIa associated with Cushing's syndrome.
AB  - Multiple Endocrine Neoplasia type IIa (MEN IIa) is an autosomal dominant syndrome
      characterized by pheochromocytoma, medullary thyroid carcinoma and
      hyperparathyroidism. Pheochromocytoma occurs in approximately 50% of patients
      with MEN IIa. This tumor has the capacity to produce ACTH ectopically and
      manifests as the Cushing syndrome, although it is very rare. We report a 26-year
      old woman patient with severe muscle weakness, skin lesions in extremities,
      hypertension, and new onset diabetes whose laboratory findings included
      hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine,
      normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as
      the first clinical manifestations of an ACTH-secreting pheochromocytoma. In the
      patients with hypertension, new onset diabetes and hypokalemia, the Cushing
      syndrome and pheochromocytoma should always be ruled out.

PMID- 24916534
TI  - Photoclinic.

PMID- 24916535
TI  - In memory of the late Alireza Afzalipour, the founder of the Kerman University.

PMID- 24916536
TI  - Docking covalent inhibitors: a parameter free approach to pose prediction and
      scoring.
AB  - Although many popular docking programs include a facility to account for covalent
      ligands, large-scale systematic docking validation studies of covalent inhibitors
      have been sparse. In this paper, we present the development and validation of a
      novel approach for docking and scoring covalent inhibitors, which consists of
      conventional noncovalent docking, heuristic formation of the covalent attachment
      point, and structural refinement of the protein-ligand complex. This approach
      combines the strengths of the docking program Glide and the protein structure
      modeling program Prime and does not require any parameter fitting for the study
      of additional covalent reaction types. We first test this method by predicting
      the native binding geometry of 38 covalently bound complexes. The average RMSD of
      the predicted poses is 1.52 A, and 76% of test set inhibitors have an RMSD of
      less than 2.0 A. In addition, the apparent affinity score constructed herein is
      tested on a virtual screening study and the characterization of the SAR
      properties of two different series of congeneric compounds with satisfactory
      success. 

PMID- 24916537
TI  - Emergence of HPV16-positive oropharyngeal cancer in Black patients over time:
      University of Maryland 1992-2007.
AB  - While we previously reported a striking racial difference in the prevalence of
      human papilloma virus (HPV)-positive squamous cell carcinoma of the oropharynx
      (OPSCC), less is known about differences in outcomes and trends over time in
      OPSCC by HPV status and race. We conducted a retrospective analysis of 467
      patients with OPSCC treated at the University of Maryland Greenebaum Cancer
      Center (Baltimore, MD) between 1992 and 2007, of which 200 had tissue available
      for HPV16 testing. HPV16-positive patients were significantly more likely to be
      white, with 45.5% of whites and 15.5% of blacks testing positive for HPV16. There
      was a significant increase in HPV16-positive OPSCC for all patients over time
      from 15.6% in 1992 to 1995 to 43.3% in 2004 to 2007 (P = 0.01). From 1992 to
      1995, 33% of white patients were HPV16-positive, with no black patients positive.
      From 2004 to 2007, 17.7% of black patients and 54% of white patients were HPV16
      positive. White and black patients with HPV16-positive tumors had an identical
      and favorable overall survival (OS; median, 8.1 and 8.1 years, respectively).
      However, among HPV16-negative patients, whites had an improved OS compared with
      blacks (median, 2.3 vs. 0.9 years, respectively; P = 0.02), including when
      analyzed in a multivariable Cox regression model. From 1992 to 2007, the
      percentage of HPV16-positive OPSCC increased for white patients and was seen for
      the first time in black patients. While survival for HPV-positive black and white
      patients was similar and favorable, outcomes for HPV-negative patients were poor,
      with blacks having worse survival even after controlling for baseline
      characteristics.

PMID- 24916538
TI  - Data Mining and Privacy of Social Network Sites' Users: Implications of the Data
      Mining Problem.
AB  - This paper explores the potential of data mining as a technique that could be
      used by malicious data miners to threaten the privacy of social network sites
      (SNS) users. It applies a data mining algorithm to a real dataset to provide
      empirically-based evidence of the ease with which characteristics about the SNS
      users can be discovered and used in a way that could invade their privacy. One
      major contribution of this article is the use of the decision forest data mining
      algorithm (SysFor) to the context of SNS, which does not only build a decision
      tree but rather a forest allowing the exploration of more logic rules from a
      dataset. One logic rule that SysFor built in this study, for example, revealed
      that anyone having a profile picture showing just the face or a picture showing a
      family is less likely to be lonely. Another contribution of this article is the
      discussion of the implications of the data mining problem for governments,
      businesses, developers and the SNS users themselves. 

PMID- 24916540
TI  - A survey of the prevalence of Nematodirus spathiger and N. filicollis on farms in
      the North and South Islands of New Zealand.
AB  - AIM: To compare the prevalence of Nematodirus spathiger and N. filicollis on a
      sample of farms in the lower South Island with the lower and central North Island
      of New Zealand by way of a presence/absence survey. METHODS: A presence/absence
      non-random survey was conducted in which pooled faeces from lambs from 50 farms
      in the lower and central North Island (n=22) and lower South Island (n=28) were
      cultured, with and without a post-culture period of chilling, to produce third
      stage parasitic nematode larvae (L3). After recovery using the Baermann
      technique, individual L3 were identified to Nematodirus spp. using a PCR assay.
      This identified the species that were present on each farm that were then used to
      compare the regions. RESULTS: Nematodirus filicollis was present in 38/50 (76%)
      samples from which Nematodirus spp. larvae were cultured, compared with 50/50
      (100%) in the case of N. spathiger. No regional differences were observed in the
      prevalence of either species (p=0.74). Of the Nematodirus spp. L3 recovered from
      the unchilled samples, 415/428 (97%) were N. spathiger and 13/428 (3%) N.
      filicollis. After chilling 594/695 (85%) of the Nematodirus spp. L3 were N.
      spathiger and 101/695 (15%) were N. filicollis. CONCLUSION: Despite the non
      random nature of the study, the evidence suggests that both these species are
      likely to occur sympatrically on most sheep farms throughout New Zealand. In
      general N. filicollis eggs did not hatch without a period of chilling and this
      has implications for the identification of these larvae using conventional
      culture methods.

PMID- 24916539
TI  - Stage of cirrhosis predicts the risk of liver-related death in patients with low
      Model for End-Stage Liver Disease scores and cirrhosis awaiting liver
      transplantation.
AB  - The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability
      in patients with cirrhosis and MELD scores <= 20. We aimed to assess whether a 5
      stage clinical model could identify liver transplantation (LT) candidates with
      low MELD scores who are at increased risk for death. We conducted a case-control
      study of subjects with cirrhosis and MELD scores <= 20 who were awaiting LT at a
      single academic medical center between February 2002 and May 2011. Conditional
      logistic regression was used to evaluate the risk of liver-related death
      according to the cirrhosis stage. We identified 41 case subjects who died from
      liver-related causes with MELD scores <= 20 within 90 days of death while they
      were waiting for LT. The cases were matched with up to 3 controls (66 controls in
      all) on the basis of the listing year, age, sex, liver disease etiology, presence
      of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for
      all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4)
      ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for
      cases and controls. Clinical states contributing to death in cases were: sepsis
      49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and
      hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio
      (OR) = 5.6, P = 0.003], albumin (OR = 0.5, P = 0.041), an increasing cirrhosis
      stage (P = 0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR =
      3.6, P = 0.048; OR = 7.4, P < 0.001; and OR = 4.1, P = 0.008), a sodium level <
      135 mmol/L (OR = 3.4, P = 0.006), and hepatic encephalopathy (OR = 2.3, P =
      0.082) were associated with liver-related death. In a multivariate model
      including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an
      increasing cirrhosis stage (P = 0.010) was independently associated with liver
      related death. In conclusion, assessing the cirrhosis stage in patients with low
      MELD scores awaiting LT may help to select candidates for more aggressive
      monitoring or for living or extended criteria donation.

PMID- 24916541
TI  - Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid,
      and selected brain regions: a systematic review and meta-analysis.
AB  - BACKGROUND: The homeostasis and physiological role of iron in Alzheimer's disease
      (AD) has been debated for decades. Overall, it has been difficult to reach a
      consensus to prove marked disease-associated changes in the iron content of the
      AD brain, blood, or cerebrospinal fluid (CSF). OBJECTIVES: We sought to
      contribute to resolve this issue by quantifying the iron content in serum, CSF,
      and sub-regions of the AD brain. METHODS: We conducted a comprehensive systematic
      meta-analysis and review of multiple observational studies till October 2013 that
      investigated the iron content in AD serum, CSF, or brain tissue. RESULTS: 2,556
      publications were screened. Forty-three eligible studies with 1,813 AD patients
      and 2,401 healthy controls were identified. Twenty-one studies investigated the
      serum iron in AD while seven and nineteen studies investigated the CSF iron and
      various brain regions iron respectively. Our meta-analysis showed that serum iron
      was significant lower in AD than healthy controls. CSF iron appeared not to be
      affected by AD although more studies are required due to the relative small
      number of CSF studies reported to date. We critically analyzed iron content in
      twelve selective brain regions by separated meta-analyses using cross-referenced
      statistical methods. We found that eight specific brain regions had higher iron
      concentrations that correlated with the clinical diagnosis of AD in a
      statistically validated manner. CONCLUSIONS: These data provided rigorous
      statistical support for the model that iron homeostasis was changed in AD
      patients, including the finding of lower iron in their serum and evidence for
      iron overload in several specific brain regions.

PMID- 24916542
TI  - Combining select neuropsychological assessment with blood-based biomarkers to
      detect mild Alzheimer's disease: a molecular neuropsychology approach.
AB  - BACKGROUND: Current work has sought to establish a rapid and cost effective means
      of screening for Alzheimer's disease (AD) with the most recent findings showing
      utility of integrating blood-based biomarkers with cognitive measures. OBJECTIVE:
      The current project sought to create a combined biomarker-cognitive profile to
      detect mild AD. METHODS: Data was analyzed from 266 participants (129 AD cases
      [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas
      Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were
      collected from each participant and assayed via a multi-plex biomarker assay
      platform using electrochemiluminescence. Logistic Regression was utilized to
      detect early AD using two serum biomarkers (TNFalpha and IL7), demographic
      information (age), and one neuropsychological measure (Clock 4-point) as
      predictor variable. Disease severity was determined via Clinical Dementia Rating
      (CDR) scale global scores. RESULTS: In the total sample (all levels of CDR
      scores), the combination of biomarkers, cognitive test score, and demographics
      yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an
      overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the
      biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall
      accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the
      biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall
      accuracy of 0.91. CONCLUSIONS: The combination of demographics, two biomarkers,
      and one cognitive test created a biomarker-cognitive profile that was highly
      accurate in detecting the presence of AD, even in the very early stages.

PMID- 24916543
TI  - Cost-effectiveness of the use of biomarkers in cerebrospinal fluid for
      Alzheimer's disease.
AB  - BACKGROUND: The use of cerebrospinal fluid (CSF) biomarkers could facilitate
      early detection of Alzheimer's disease (AD) in patients with mild cognitive
      impairment (MCI) and the differential diagnosis between AD and non-AD dementias.
      OBJECTIVE: To determine the cost-effectiveness of the use of amyloid-beta peptide
      (Abeta42), total tau and phosphorylated tau proteins in CSF to diagnose AD in MCI
      and dementia patients. METHODS: An economic evaluation was performed by means of
      cost-effectiveness analysis comparing two AD diagnostic alternatives: the
      combined determination of Abeta42 proteins, total tau and phosphorylated tau in
      CSF as biomarkers of AD, and the standard clinical diagnosis based on the
      National Institute of Neurological and Communicative Disorders and Stroke and the
      Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria. A
      decision analytic model was developed to synthesize the identified evidence and
      to compare the costs and effectiveness associated with each diagnostic strategy.
      A probabilistic sensitivity analysis using 2nd order Monte Carlo simulations was
      performed. Subsequently, acceptability curves were calculated and ANCOVA models
      were applied to the results of the Monte Carlo simulations in order to identify
      the parameters that led greater variability in the model outcomes. RESULTS: The
      use of CSF biomarkers as an early diagnostic strategy of AD in MCI patients is a
      dominant alternative (less costly and more effective strategy than standard
      clinical diagnostic criteria). In dementia patients, although there is a higher
      uncertainty, biomarkers in CSF seem a more cost-effective alternative than
      standard clinical diagnostic criteria. CONCLUSIONS: Detecting AD in MCI patients
      by determining Abeta42, total tau and phosphorylated tau proteins biomarkers in
      CSF is a cost-effective diagnostic alternative. No conclusive results were
      obtained on dementia patients.

PMID- 24916544
TI  - Cooperative therapeutic action of retinoic acid receptor and retinoid x receptor
      agonists in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative process involving amyloid-beta
      (Abeta) peptide deposition, neuroinflammation, and progressive memory loss. Here,
      we evaluated whether oral administration of retinoic acid receptor
      (RAR)alpha,beta agonist Am80 (tamibarotene) or specific retinoid X receptor (RXR)
      pan agonist HX630 or their combination could improve deficits in an AD model, 8.5
      month-old amyloid-beta protein precursor 23 (AbetaPP23) mice. Co-administration
      of Am80 (0.5 mg/kg) and HX630 (5 mg/kg) for 17 days significantly improved memory
      deficits (Morris water maze) in AbetaPP23 mice, whereas administration of either
      agent alone produced no effect. Only co-administration significantly reduced the
      level of insoluble Abeta peptide in the brain. These results thus indicate that
      effective memory improvement via reduction of insoluble Abeta peptide in 8.5
      month-old AbetaPP23 mice requires co-activation of RARalpha,beta and RXRs.
      RARalpha-positive microglia accumulated Abeta plaques in the AbetaPP23 mice. Rat
      primary microglia co-treated with Am80/HX630 showed increased degradation
      activity towards 125I-labeled oligomeric Abeta1-42 peptide in an insulin
      degrading enzyme (IDE)-dependent manner. The co-administration increased mRNA for
      IDE and membrane-associated IDE protein in vivo, suggesting that IDE contributes
      to Abeta clearance in Am80/HX630-treated AbetaPP23 mice. Am80/HX630 also
      increased IL-4Ralpha expression in microglial MG5 cells. The improvement in
      memory of Am80/HX630-treated AbetaPP23 mice was correlated with the levels and
      signaling of hippocampal interleukin-4 (IL-4). Therefore, Am80/HX630 may promote
      differentiation of IL-4-responsive M2-like microglia and increase their activity
      for clearance of oligomeric Abeta peptides by restoring impaired IL-4 signaling
      in AbetaPP23 mice. Combination treatment with RAR and RXR agonists may be an
      effective approach for AD therapy. 

PMID- 24916545
TI  - Anti-EGFR MoAb treatment in colorectal cancer: limitations, controversies, and
      contradictories.
AB  - Anti-epidermal growth-factor receptor (EGFR) monoclonal antibody (MoAb) treatment
      for chemotherapy refractory or metastatic colorectal cancer has obtained great
      achievement. However, not every colorectal patient responds to such molecular
      targeted agent well. Biomarkers associated with anti-EGFR resistance are not
      limited to KRAS mutation up to now. It was recently reported that cross-talking
      molecular effectors interacted with EGFR-related pathway were also negative
      predictor for anti-EGFR treatment. However, the limited data, controversial
      results, and contradictories between in vitro and clinical studies restrict the
      clinical application of these new biomarkers. Although the current theory of
      tumor microenvironment supported the application of multi-target treatment, the
      results from the clinical studies were less than expected. Moreover, WHO or
      RECIST guideline for response assessment in anti-EGFR MoAb treatment was also
      queried by recent AIO KRK-0306 trial. This review focuses on these controversies,
      contradictories, and limitations, in order to uncover the unmet needs in current
      status of anti-EGFR MoAb treatment in colorectal cancer. 

PMID- 24916546
TI  - A phase I study of pegylated liposomal doxorubicin and temsirolimus in patients
      with refractory solid malignancies.
AB  - This study aimed to determine the maximum-tolerated dose and dose-limiting
      toxicities of pegylated liposomal doxorubicin (PLD) in combination with
      temsirolimus (T) in patients with refractory solid tumors. Using a standard "3+3"
      dose escalation design, 23 patients were enrolled in three dosing cohorts in this
      phase I study. The starting dose level was PLD at 30 mg/m(2) every 4 weeks and T
      at 20 mg weekly. Pharmacokinetics (PK) of doxorubicin were evaluated for patients
      in the expansion cohort. The most common treatment-related adverse events of all
      grades were mucositis/stomatitis (69.6%), anorexia (52.2%), thrombocytopenia
      (52.2%), and fatigue (47.8%). The recommended doses of this combination for phase
      II studies are 25 mg/m(2) PLD and 25 mg T. PK analyses suggested increased
      exposure of doxorubicin in this combination regimen compared to doxorubicin
      administered as a single agent, possibly due to PK drug interactions. Out of 18
      patients evaluable for a treatment response, two had partial responses (PR)
      (breast cancer and hepatocellular carcinoma) and six had stable disease (SD). Two
      patients remained on treatment for more than 1 year. The combination of PLD and T
      is tolerable, and the treatment resulted in clinical benefit. The combination
      regimen should be further explored in appropriate tumor types.

PMID- 24916547
TI  - Supplementation of fish oil augments efficacy and attenuates toxicity of 5
      fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium
      induced colon carcinogenesis.
AB  - PURPOSE: 5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer,
      but has low therapeutic response rate and severe side effects. Recently, fish oil
      (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize
      tumor cells to anticancer drugs. Therefore, the current study is designed to
      evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination
      with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)
      induced colon cancer model. METHODS: The therapeutic efficacy of 5-FU along with
      FO was analyzed through assessment of survival rate, tumor burden, volume, serum
      sialic acid levels, cytokeratin 19 (CK19) expression and index of cell
      proliferation such as cell cycle progression. Toxicological aspects were
      evaluated by standard functional and structural parameters related to spleen,
      gastrointestinal, liver and kidney. RESULTS: In the present study, 5-FU in
      combination with FO increased the survival rate in carcinogen-treated animals.
      Synergism of 5-FU and FO was also reflected in significant inhibition in tumor
      growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination
      dosage significantly augmented the inhibition of cell cycle progression, as shown
      by CK19 expression. Additionally, FO ameliorated hematologic depression,
      gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a
      marked improvement in structural and functional alterations of these organs.
      CONCLUSION: The supplementation of FO is potentially a promising option for
      increasing the therapeutic potential and mitigating the side effects of 5-FU.

PMID- 24916549
TI  - Iterative trapping of gaseous volatile organic compounds in a capillary column.
AB  - The iterative trapping method has been developed for concentrating gaseous
      volatile organic compounds (VOCs) prior to gas chromatographic analysis. VOCs are
      trapped in a 50 cm * 0.53 mm metal capillary column coated with a 7 MUm thick
      film of polydimethylsiloxane (PDMS). Iterative trapping does not employ the two
      step thermal desorption approach used by most VOC concentrating techniques.
      Instead, a four-step cycle involving synchronized changes in flow direction and
      temperature is repeated throughout the sampling process. This iterative process
      causes VOCs to accumulate within the capillary well past the level where a
      standard two-step method reaches its saturation limit. Iterative trapping is
      capable of sampling and desorbing C5 through C11 n-alkanes with uniform
      efficiency. This new technique, in its current form, is most appropriate for
      focusing VOCs from gas volumes on the order of 10 mL. Iterative trapping
      increases the focusing power of a weak sorbent like PDMS and allows narrow
      chromatographic peaks to be generated without the use of high desorption
      temperatures or a secondary focusing stage. 

PMID- 24916548
TI  - Venous thromboembolism in patients undergoing shoulder surgery: findings from the
      RECOS Registry.
AB  - BACKGROUND: Limited informations are available about venous thromboembolic (VTE)
      complications and thromboprophylaxis use after shoulder surgery. The primary end
      point of the study was to determine the incidence of symptomatic deep vein
      thrombosis (DVT) and pulmonary embolism (PE) within 90days after shoulder
      surgery. Risk factors for VTE and thromboprophylaxis practices were also studied.
      METHODS: RECOS is a prospective multicenter registry of consecutive patients
      undergoing shoulder surgery recruited in nine hospitals in Italy. Cumulative
      rates of VTE were estimated according to the Kaplan-Meier method; a Cox
      regression model was used to calculate adjusted hazard ratio (HR) and 95%
      confidence interval (CI) for some variables that were identified as risk factors
      for VTE. RESULTS: From June 2009 to June 2011 1366 patients (males 54.4%; mean
      age 55,65+/-15.3years) were enrolled. The surgical procedures were: arthroscopy
      (71.9%), hemiarthroplasty (17.2%) total replacement (8.9%), fixation for proximal
      humeral fracture (2%). After 90days, the incidence of symptomatic VTE was 0.66%
      (95CI% 0.2-1.12). Mean age was significantly higher in patient with than in
      patients without VTE (67,1+/3.49years vs 55,6+/-0,42years, respectively;
      p=0.024). Duration of surgery>60minutes (HR:10.99; 95CI% 1.26-95.89; p=0.030) was
      found as independent risk factor for VTE, while cancer, medical disease, venous
      insufficiency and previous VTE were not. Pharmacological thromboprophylaxis was
      prescribed in 33.5% (n=457) of the patients, in 95.8% of whom for a duration
      >10days. CONCLUSIONS: The risk of symptomatic VTE in patients undergoing shoulder
      surgery is low. The potential need for thromboprophylaxis should be based on a
      case by case evaluation.

PMID- 24916550
TI  - Liver function parameters, cholesterol, and phospholipid alpha-linoleic acid are
      associated with adipokine levels in overweight and obese adults.
AB  - Dysregulation of adipose hormones in obesity has been associated with the
      hastened development of metabolic syndrome and associated chronic disease
      sequalae including cardiovascular disease and type 2 diabetes mellitus. This
      study aims to identify common biochemical and anthropometric markers that impact
      adipose hormones, including adiponectin and leptin. Based on previous literature,
      it was hypothesized that these would be adversely impacted by liver function
      parameters, and adiponectin levels would be positively correlated with
      phospholipid Omega-3 fatty acids. Forty nondiabetic adult subjects (body mass
      index, >= 25.0 kg/m(2)) were recruited. Fasting plasma samples were taken to
      assess adipokine levels, glucose metabolism, electrolytes, liver enzymes, and
      blood lipids. Basic anthropometric measurements were also recorded. Adiponectin
      levels were positively correlated with high-density lipoprotein cholesterol and
      negatively correlated with anthropometric measures, insulin, liver enzymes,
      triglycerides, and very low-density lipoprotein cholesterol but not body mass
      index. Conversely, plasma leptin levels were positively correlated with
      anthropometric measures, C-reactive protein, high-density lipoprotein
      cholesterol, and plasma phospholipid proportions of Omega-3 alpha linoleic acid
      but inversely correlated with creatinine levels. These results support other data
      regarding correlations between adiponectin and relative adipose distribution.
      Correlations with specific liver enzymes may indicate that adiponectin levels are
      tied to fatty acid deposition in the liver; however, liver/kidney damage though
      further mechanistic clarification is required. Leptin levels were associated with
      measures of adiposity but not liver enzymes. Each of these variables, along with
      blood lipids, may serve as potential future therapeutic targets for the
      prevention and management of obesity and related comorbidities.

PMID- 24916551
TI  - Three distinct clustering patterns in metabolic syndrome abnormalities are
      differentially associated with dietary factors in Korean adults.
AB  - Dietary factors are not consistently associated with metabolic syndrome
      abnormalities. In this cross-sectional study, we hypothesized that distinct
      clustering patterns exist in metabolic syndrome abnormalities and that those
      patterns are differentially associated with dietary factors. To test this
      hypothesis, we examined distinct clustering patterns of metabolic syndrome
      abnormalities and their association with dietary factors in Korean adults. A
      total of 141 subjects were recruited through the Family Medicine Division of the
      General Hospital in Seoul. Subjects who had complete data on waist circumference,
      blood pressure, blood glucose and lipid indicators, and no medication usage were
      included in this study. Dietary intake data were obtained by multiple 24-hour
      recalls (2-4 days) through on-site or telephone interviews. To identify
      clustering patterns of metabolic syndrome abnormalities, factor analysis was used
      for waist circumference, systolic and diastolic blood pressure, blood glucose,
      triglycerides, and high-density lipoprotein cholesterol. Three distinct
      clustering patterns were identified: (1) high blood pressure, (2) dyslipidemia,
      and (3) high blood glucose. The high blood pressure pattern was significantly
      associated with higher alcohol intake and lower carbohydrate intake. The
      dyslipidemia pattern was significantly associated with a diet of high glycemic
      index and glycemic load. The high blood glucose pattern was associated with lower
      carbohydrate intake. Metabolic syndrome abnormalities had 3 distinct clustering
      patterns independently associated with dietary factors. Diets with high glycemic
      index and glycemic load were strongly linked with the dyslipidemia pattern, and
      high alcohol intake was linked with the high blood pressure pattern in Korean
      adults. 

PMID- 24916552
TI  - Postprandial oxidative stress is increased after a phytonutrient-poor food but
      not after a kilojoule-matched phytonutrient-rich food.
AB  - Research indicates that energy-dense foods increase inflammation and oxidative
      activity, thereby contributing to the development of vascular disease. However,
      it is not clear whether the high kilojoule load alone, irrespective of the
      nutritional content of the ingested food, produces the postprandial oxidative and
      inflammatory activity. This study investigated the hypothesis that ingestion of a
      high-fat, high-sugar, phytonutrient-reduced food (ice cream) would increase
      oxidative and inflammatory activity greater than a kilojoule-equivalent meal of a
      phytonutrient-rich whole food (avocado). The individual contributions of the
      fat/protein and sugar components of the ice cream meal to postprandial
      inflammation and oxidative stress were also quantified. Using a randomized,
      crossover design, 11 healthy participants ingested 4 test meals: ice cream,
      avocado, the fat/protein component in ice cream, and the sugar equivalent
      component in ice cream. Plasma glucose, cholesterol, triglycerides, and
      inflammatory and oxidative stress markers were measured at baseline and 1, 2, and
      4 hours (t1, t2, t4) after ingestion. Lipid peroxidation was increased at 2 hours
      after eating fat/protein (t0-t2, P < .05) and sugar (t1-t2, P < .05; t1-t4, P <
      .05). Antioxidant capacity was decreased at 4 hours after eating ice cream (t0
      t4, P < .01) and sugar (t0-t4, P < .01). Ingestion of a kilojoule-equivalent
      avocado meal did not produce any changes in either inflammatory or oxidative
      stress markers. These data indicate that the ingestion of a phytonutrient-poor
      food and its individual fat/protein or sugar components increase plasma oxidative
      activity. This is not observed after ingestion of a kilojoule-equivalent
      phytonutrient-rich food. 

PMID- 24916554
TI  - Validity and reproducibility of an interviewer-administered food frequency
      questionnaire in Austrian adults at risk of or with overt diabetes mellitus.
AB  - Food frequency questionnaires (FFQs) provide an inexpensive tool for dietary
      assessment. Given the scarcity of data on their validity for nutritional analysis
      in persons with overt diabetes mellitus or with increased risk of diabetes
      (relatives of patients with diabetes), this study tests the hypothesis that an
      FFQ, adapted to local dietary habits, yields a reliable estimate of nutrient
      intake when compared with 7-day food record (7DR) in healthy, prediabetes, and
      diabetes cohorts. One hundred three volunteers (50 persons with overt diabetes
      mellitus, 24 relatives of patients with diabetes, and 29 nondiabetic individuals
      without a family history of diabetes) completed both FFQ and 7DR. A second FFQ
      was completed by 100 of these volunteers after 3 months to evaluate its
      reproducibility. Data were compared by correlation and Bland-Altman analyses.
      Across the entire group, estimates for gram intakes of nutrients and total energy
      were associated with wide limits of agreement between FFQ and 7DR (correlation
      coefficients, 0.23-0.72; P < .02). Compared with 7DR, the FFQ overestimated
      intakes of saturated fat in the entire group (+6.6 +/- 14 g; P < .001) and in
      persons with overt diabetes mellitus (+7.6 +/- 15 g; P < .001) but underestimated
      protein intake in relatives of patients with diabetes (-16.36 +/- 31 g; P = .01).
      The repeated FFQ revealed variable agreement (correlation coefficients, 0.34
      0.72; P < .001) and underestimated (P < .01) macronutrient and total energy
      intakes, with slightly better performance in persons with overt diabetes mellitus
      and relatives of patients with diabetes than in nondiabetic individuals without a
      family history of diabetes. Hence, the FFQ allows measuring intakes of total
      energy and macronutrients in prediabetes and diabetes cohorts but reveals
      limitations when assessing dietary composition. 

PMID- 24916553
TI  - S-(-)equol production is developmentally regulated and related to early diet
      composition.
AB  - S-(-)7-hydroxy-3-(4'-hydroxyphenyl)-chroman, or S-(-)equol, a biologically active
      intestinally derived bacterial metabolite of the soy isoflavones
      daidzin/daidzein, is not produced in neonatal life. Because its synthesis is
      dependent on equol-producing bacteria, we hypothesized that early nutrition may
      influence equol production. This prospective 2.5-year study determined the
      frequency of S-(-)equol production in healthy infants (n = 90) fed breast milk,
      soy infant formula, or cow's milk formula in their first year. Urinary S-(-)equol
      and daidzein were quantified by mass spectrometry after a standardized 3.5-day
      soy isoflavone challenge. Infants were tested at 6, 9, 12, 18, 24, and 36 months
      of age, and 3-day diet records were obtained at each visit to explore the effect
      of early and postweaning (>12 months) macronutrient and micronutrient dietary
      composition and S-(-)equol production. Use of antibiotics was also recorded. At
      age 6 months, none of the breast-fed infants produced S-(-)equol, whereas 3.8%
      and 6.0%, respectively, of soy and cow's milk formula-fed infants were equol
      producers. By age 3 years, 50% of the formula-fed infants were equol producers,
      compared with 25% of breast-fed infants. Use of antibiotics was prevalent among
      infants and may have impacted the stability of S-(-)equol production. No
      significant differences among the groups were observed in postweaning dietary
      intakes of total energy, carbohydrate, fiber, protein, fat, saturated fatty
      acids, or polyunsaturated fatty acids and the propensity to make S-(-)equol. In
      conclusion, S-(-)equol production is developmentally regulated and initially
      related to diet composition with the proportion of equol producers increasing
      over the first 3 years of life, with a trend for formula feeding favoring S-(
      )equol production. 

PMID- 24916555
TI  - Consumption of cranberry beverage improved endogenous antioxidant status and
      protected against bacteria adhesion in healthy humans: a randomized controlled
      trial.
AB  - Consumption of polyphenol-rich foods is associated with lower risk from many
      chronic diseases. We hypothesized that a single dose of cranberry beverage would
      improve indices of oxidative stress, inflammation, and urinary antibacterial
      adhesion activity in healthy humans. Six males and 6 females (18-35 years; body
      mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or
      low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind,
      placebo-controlled cross-over experimental design trial. The washout period
      between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after
      beverage consumption for measuring oxidative and inflammatory biomarkers. Urine
      was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours
      postintervention to assess antibacterial adhesion activity. Consumption of
      cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase
      activity, whereas LCJC consumption increased (P < .05) glutathione concentrations
      and superoxide dismutase activity compared with placebo. Cranberry leaf extract
      beverage and LCJC consumption had no effect on the inflammatory biomarkers
      measured as compared with placebo. At 0 to 3 hours postconsumption, urine from
      participants who consumed cranberry beverages had higher (P < .05) ex vivo
      antiadhesion activity against P-fimbriated Escherichia coli compared with
      placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant
      status and inhibition of bacterial adhesion in urine. 

PMID- 24916556
TI  - Intensively managed young children with type 1 diabetes consume high-fat, low
      fiber diets similar to age-matched controls.
AB  - Despite significant emphasis on nutrition, older children with diabetes
      demonstrate poor dietary quality. We tested the hypothesis that dietary quality
      in young children with type 1 diabetes (T1D) would be better than age-matched
      children in the US population. Dietary data from children with T1D (n = 67) aged
      2 to 12 years attending a pediatric diabetes clinic were compared with a
      nationally representative, age-matched sample from the National Health and
      Nutrition Examination Survey (NHANES; n = 1691). Multiple 24-hour dietary recalls
      were used. Recommended intakes were based on national guidelines, and dietary
      quality was assessed using the Healthy Eating Index-2005. More children with T1D
      were overweight or obese compared with children participating in NHANES (42% vs
      30%, P = .04). Greater proportions of children with T1D met daily recommendations
      for vegetables (22% vs 13%, P = .03), whole grains (12% vs 5%, P = .005), and
      dairy (55% vs 36%, P = .001) compared with NHANES children, whereas similar
      proportions met daily fruit recommendations (40% vs 33%, P = .2). Less than one
      third of all children limited total fat to recommended levels; children with T1D
      consumed more saturated fat than did NHANES children (14% vs 12% total energy
      intake, P = .0009). Fiber intakes were very low in both groups. Compared with
      NHANES children, children with T1D had higher Healthy Eating Index-2005 scores
      (59.6 vs 49.7, P = .0006) primarily because of lower intakes of added sugars. The
      nutritional intake of young children with T1D remains suboptimal in the
      contemporary era of diabetes management. Despite focused nutrition management,
      young children with T1D consume high-fat, low-fiber diets comparable with youth
      in the general population. 

PMID- 24916557
TI  - Swedish children with celiac disease comply well with a gluten-free diet, and
      most include oats without reporting any adverse effects: a long-term follow-up
      study.
AB  - The only known treatment for celiac disease is a gluten-free diet (GFD), which
      initially meant abstention from wheat, rye, barley, and oats. Recently, oats free
      from contamination with wheat have been accepted in the GFD. Yet, reports
      indicate that all celiac disease patients may not tolerate oats. We hypothesized
      that celiac children comply well with a GFD and that most have included oats in
      their diet. A food questionnaire was used to check our patients; 316
      questionnaires were returned. Mean time on the GFD was 6.9 years, and 96.8% of
      the children reported that they were trying to keep a strict GFD. However,
      accidental transgressions occurred in 263 children (83.2%). In 2 of 3 cases,
      mistakes took place when the patients were not at home. Symptoms after incidental
      gluten intake were experienced by 162 (61.6%) patients, mostly (87.5%) from the
      gastrointestinal tract. Small amounts of gluten (<4 g) caused symptoms in 38% of
      the cases, and 68% reported symptoms during the first 3 hours after gluten
      consumption. Oats were included in the diet of 89.4% of the children for a mean
      of 3.4 years. Most (81.9%) ate purified oats, and 45.3% consumed oats less than
      once a week. Among those who did not consume oats, only 5.9% refrained because of
      symptoms. General compliance with the GFD was good. Only the duration of the GFD
      appeared to influence adherence to the diet. Most patients did not report adverse
      effects after long-term consumption of oats. 

PMID- 24916558
TI  - Ingesting a preworkout supplement containing caffeine, creatine, beta-alanine,
      amino acids, and B vitamins for 28 days is both safe and efficacious in
      recreationally active men.
AB  - The purpose of this study was to determine the safety and efficacy of consuming a
      preworkout supplement (SUP) containing caffeine, creatine, beta-alanine, amino
      acids, and B vitamins for 28 days. We hypothesized that little to no changes in
      kidney and liver clinical blood markers or resting heart rate and blood pressure
      (BP) would be observed. In addition, we hypothesized that body composition and
      performance would improve in recreationally active males after 28 days of
      supplementation. In a double-blind, placebo-controlled study, participants were
      randomly assigned to ingest one scoop of either the SUP or placebo every day for
      28 days, either 20 minutes before exercise or ad libitum on nonexercise days.
      Resting heart rate and BP, body composition, and fasting blood samples were
      collected before and after supplementation. Aerobic capacity as well as muscular
      strength and endurance were also measured. Significant (P < .05) main effects for
      time were observed for resting heart rate (presupplementation, 67.59 +/- 7.90
      beats per minute; postsupplementation, 66.18 +/- 7.63 beats per minute), systolic
      BP (presupplementation, 122.41 +/- 11.25 mm Hg; postsupplementation, 118.35 +/-
      11.58 mm Hg), blood urea nitrogen (presupplementation, 13.12 +/- 2.55 mg/dL;
      postsupplementation, 15.24 +/- 4.47 mg/dL), aspartate aminotransferase
      (presupplementation, 34.29 +/- 16.48 IU/L; postsupplementation, 24.76 +/- 4.71
      IU/L), and alanine aminotransferase (presupplementation, 32.76 +/- 19.72 IU/L;
      postsupplementation, 24.88 +/- 9.68 IU/L). Significant main effects for time were
      observed for body fat percentage (presupplementation, 15.55% +/- 5.79%;
      postsupplementation, 14.21% +/- 5.38%; P = .004) and fat-free mass
      (presupplementation, 70.80 +/- 9.21 kg; postsupplementation, 71.98 +/- 9.27 kg; P
      = .006). A significant decrease in maximal oxygen consumption
      (presupplementation, 47.28 +/- 2.69 mL/kg per minute; postsupplementation, 45.60
      +/- 2.81 mL/kg per minute) and a significant increase in percentage of oxygen
      consumption per unit time at which ventilatory threshold occurred
      (presupplementation, 64.38% +/- 6.63%; postsupplementation, 70.63% +/- 6.39%) and
      leg press one-repetition maximum (presupplementation, 218.75 +/- 38.43 kg;
      postsupplementation, 228.75 +/- 44.79 kg) were observed in the SUP only. No
      adverse effects were noted for renal and hepatic clinical blood markers, resting
      heart rate, or BP. Supplements containing similar ingredients and doses should be
      safe for ingestion periods lasting up to 28 days in healthy, recreationally
      trained, college-aged men.

PMID- 24916559
TI  - Olive leaf extract suppresses messenger RNA expression of proinflammatory
      cytokines and enhances insulin receptor substrate 1 expression in the rats with
      streptozotocin and high-fat diet-induced diabetes.
AB  - Type 2 diabetes, characterized by hyperglycemia and hyperlipidemia, is a
      metabolic disease resulting from defects in both insulin secretion and insulin
      resistance. Recently, olive leaf has been reported as an anti-inflammatory,
      antioxidant, and antidiabetic agent. This study sought to investigate whether
      olive leaf extract can improve the insulin resistance and inflammation response
      in rats with type 2 diabetes induced by high-fat diet and streptozotocin. After
      administering olive leaf extract for 8 weeks (200 and 400 mg/kg body weight),
      rats given the higher dose showed significantly lower blood glucose, serum total
      cholesterol, and triglyceride levels compared with those of diabetic control rats
      (P < .05). Results of oral glucose tolerance tests, homeostasis model assessment
      of insulin resistance, and messenger RNA (mRNA) expression of tumor necrosis
      factor alpha and interleukin (IL) 6 in the liver show significantly decreased
      glucose level in rats given either dose of olive leaf extract (P < .05). Both
      olive leaf extract-treated groups showed significantly increased insulin receptor
      substrate 1 expression (P < .05). Tumor necrosis factor alpha, IL-6 and IL-1beta
      mRNA expressions in epididymis adipose tissue were significantly lower in rats
      that received higher dose of olive leaf extract (P < .05). Lymphocyte
      infiltration was not observed in these rats. The results suggest that olive leaf
      extract may attenuate insulin resistance by suppressing mRNA expression of
      proinflammatory cytokines and elevating of insulin receptor substrate 1
      expression. 

PMID- 24916560
TI  - Corn gluten hydrolysate and capsaicin have complimentary actions on body weight
      reduction and lipid-related genes in diet-induced obese rats.
AB  - The aim of this study was to test the hypothesis that a combination of corn
      gluten hydrolysate (CGH) and capsaicin may have an additive or synergistic effect
      on body weight reduction. For 13 weeks, male Sprague-Dawley rats were provided a
      diet to induce obesity. Afterward, the rats were randomly divided into 5 dietary
      groups: the normal control (n = 5), the high-fat control (n = 8), the high-fat
      diet (HFD) containing 35% CGH (n = 7), the HFD containing 0.02% capsaicin (HF-P)
      (n = 8), and the HFD containing both CGH and capsaicin (HF-CP) (n = 7) for an
      additional 4 weeks. Administration of CGH plus capsaicin, along with a HFD, led
      to significant decreases in body weight, fat mass, lipids in the liver, and
      plasma leptin as well as increases in plasma adiponectin. The pattern of gene
      expression was different in each target organ. In the liver, up-regulation of
      peroxisome proliferator-activated receptor alpha, carnitine palmitoyltransferase
      1alpha, and acyl-coenzyme A oxidase was found in the HF-CP group. In contrast,
      down-regulation of peroxisome proliferator-activated receptor gamma was found in
      both the HFD containing 35% CGH and HF-CP groups. In skeletal muscle, up
      regulation of insulin receptor and uncoupling protein 3 was found in the HF-P
      group only, whereas up-regulation of the glucose transporter 4 gene was observed
      in both the HF-CP and HF-P groups. In adipose tissue, up-regulation of peroxisome
      proliferator-activated receptor gamma and hormone-sensitive lipase was only found
      in the HF-CP group. In summary, this study suggests that CGH and capsaicin
      perform complementary actions on food intake, lipid metabolism, and insulin
      sensitivity by a coordinated control of energy metabolism in the liver, adipose
      tissue, and skeletal muscle, thus exerting an additive effect on body weight
      reduction. 

PMID- 24916561
TI  - Comparison of maternal and umbilical cord blood soluble lectin-like oxidized low
      density lipoprotein receptor 1 levels in early- and late-onset preeclampsia.
AB  - BACKGROUND: The main purpose of this study was to determine the maternal and
      umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low
      density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset
      preeclampsia (PE). MATERIALS AND METHODS: A case-control study was conducted in
      pregnant women with early-onset (before 34 weeks' gestation n = 19) and late
      onset (after 34 weeks' gestation n = 22) PE compared to healthy normotensive
      pregnant controls (n = 44). Groups were compared for the maternal and umbilical
      cord plasma oxLDL and serum sLOX-1 levels. RESULTS: The mean maternal and
      umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased
      in early- and late-onset PE compared to controls (p < 0.001). When early- and
      late-onset PE women were compared with serum sLOX-1 levels, the increase was more
      pronounced in early PE (p < 0.001). However, same comparison is not statistically
      significant in cord blood for oxLDL where as it is significantly higher in
      maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL
      and sLOX-1 levels are positively correlated with each other; however, they are
      negatively correlated with fetal weight and gestational age. CONCLUSIONS:
      According to our results, maternal and umbilical cord blood levels of oxLDL and
      sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been
      shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as
      plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying
      than oxLDL for the differentiation of early and late preeclampsia.

PMID- 24916562
TI  - Modeling insurer-homeowner interactions in managing natural disaster risk.
AB  - The current system for managing natural disaster risk in the United States is
      problematic for both homeowners and insurers. Homeowners are often uninsured or
      underinsured against natural disaster losses, and typically do not invest in
      retrofits that can reduce losses. Insurers often do not want to insure against
      these losses, which are some of their biggest exposures and can cause an
      undesirably high chance of insolvency. There is a need to design an improved
      system that acknowledges the different perspectives of the stakeholders. In this
      article, we introduce a new modeling framework to help understand and manage the
      insurer's role in catastrophe risk management. The framework includes a new game
      theoretic optimization model of insurer decisions that interacts with a utility
      based homeowner decision model and is integrated with a regional catastrophe loss
      estimation model. Reinsurer and government roles are represented as bounds on the
      insurer-insured interactions. We demonstrate the model for a full-scale case
      study for hurricane risk to residential buildings in eastern North Carolina;
      present the results from the perspectives of all stakeholders-primary insurers,
      homeowners (insured and uninsured), and reinsurers; and examine the effect of key
      parameters on the results. 

PMID- 24916563
TI  - Medium composition for effective slow freezing of embryonic cell lines derived
      from marine medaka (Oryzias dancena).
AB  - This study was conducted to identify optimal medium composition for freezing
      Oryzias dancena embryonic cell lines. Different freezing media consisting of
      various concentration of dimethyl sulfoxide (DMSO), fetal bovine serum (FBS), and
      trehalose were prepared and long-term cultured embryonic cell line was frozen in
      each freezing medium by conventional slow freezing program for 7 days. Through
      measurement of viability and growth of post-thaw cells frozen in each freezing
      medium, it was determined that optimal composition of three components was 10 %
      DMSO, 20 % FBS, and 0.1 M trehalose. The post-thaw cells frozen in optimal
      freezing medium showed similar morphology and growth rate with non-frozen cells.
      Next, this condition was applied to two different sets of experiment; (1)
      freezing of the same cells during expanded period (57 days) and (2) freezing of
      short-term cultured cells from other batches for 7 days. The viability of post
      thaw cells was significantly low and comparable in set 1 and 2, respectively,
      when compared with the result of long term-cultured cells frozen in optimal
      freezing medium for 7 days and similar morphology and growth rate with non-frozen
      counterparts were detected in the post-thaw cells from both sets. In conclusion,
      this study first reports the optimal medium composition for freezing O. dancena
      embryonic cells, which can contribute to fish species preservation as well as
      improvement of cell-based biotechnology by providing stable cell storage. 

PMID- 24916564
TI  - Pituitary apoplexy during pregnancy: a rare, but dangerous headache.
AB  - Pituitary apoplexy is a rare endocrine emergency that occurs in a small number of
      patients with a pituitary tumor. It is a clinical syndrome characterized by the
      sudden onset of headache, nausea, vomiting, visual impairment, and decreased
      consciousness, caused by hemorrhage and/or infarction of the pituitary gland.
      Pituitary apoplexy has very rarely been described during pregnancy, when it is
      potentially life-threatening to both the mother and the fetus, if unrecognized.
      Only a few cases have been published to date. The review of the existing
      literature underlines that pituitary apoplexy, although rare, should be borne in
      mind when a pregnant woman presents with severe headache and visual defects of
      sudden onset. After initial management, which includes intravenous glucocorticoid
      therapy, fluid and electrolyte replacement, the final selection of medical or
      surgical treatment should result from a multidisciplinary approach involving
      expert specialists, keeping into account both severity of clinical presentation
      and gestational week. 

PMID- 24916565
TI  - Altered expression of 3-betahydroxysterol delta-24-reductase/selective
      Alzheimer's disease indicator-1 gene in Huntington's disease models.
AB  - INTRODUCTION: 3-betahydroxysterol delta-24-reductase (DHCR24), also called
      selective Alzheimer's disease indicator-1, is a crucial enzyme in cholesterol
      biosynthesis with neuroprotective properties that is downregulated in brain areas
      affected by Alzheimer's disease. AIM: In the present study, we investigated
      modifications of DHCR24 expression in models of Huntington's disease (HD), a
      neurodegenerative disorder caused by a polyglutamine expansion in huntingtin
      (Htt) protein that induces degeneration of cerebral cortex and striatum as well
      as lateral hypothalamic abnormality. METHODS: Basal expression of DHCR24 and its
      modulation after oxidative stress were evaluated in rat striatal precursors cells
      (ST14A) transfected with wild-type (Htt) or mutant Htt (mHtt) and in brain tissue
      of an HD mouse model (R6/2). RESULTS: The results showed that DHCR24 transcript
      levels were decreased in ST14A cells expressing mHtt and in the brain of
      symptomatic R6/2 mice, but were significantly increased in ST14A cells
      overexpressing wild-type Htt. In addition, we demonstrated that, in the striatal
      precursors, the decrease of DHCR24 expression in response to oxidative stress was
      modified according to the presence of Htt or of its mutant form. Preliminary
      results indicated a modification of DHCR24 expression in post-mortem brain
      samples of HD patients. CONCLUSIONS: In conclusion, these results support the
      hypothesis of a possible role of DHCR24 in HD.

PMID- 24916567
TI  - A systematic review of eHealth interventions to improve health literacy.
AB  - Implementation of eHealth is now considered an effective way to address concerns
      about the health status of health care consumers. The purpose of this study was
      to review empirically based eHealth intervention strategies designed to improve
      health literacy among consumers in a variety of settings. A computerized search
      of 16 databases of abstracts (e.g. Biomedical Reference Collection, Cochrane
      Central Register of Controlled Trials, Computers & Applied Sciences Complete,
      Health Technology Assessments, MEDLINE) were explored in a systematic fashion to
      assess the presence of eHealth applications targeting health literacy. Compared
      to control interventions, the interventions using technology reported significant
      outcomes or showed promise for future positive outcomes regarding health literacy
      in a variety of settings, for different diseases, and with diverse samples. This
      review has indicated that it is feasible to deliver eHealth interventions
      specifically designed to improve health literacy skills for people with different
      health conditions, risk factors, and socioeconomic backgrounds.

PMID- 24916566
TI  - Predictors of fatality in pandemic influenza A (H1N1) virus infection among
      adults.
AB  - BACKGROUND: The fatality attributed to pandemic influenza A H1N1 was not clear in
      the literature. We described the predictors for fatality related to pandemic
      influenza A H1N1 infection among hospitalized adult patients. METHODS: This is a
      multicenter study performed during the pandemic influenza A H1N1 [A(H1N1)pdm09]
      outbreak which occurred in 2009 and 2010. Analysis was performed among laboratory
      confirmed patients. Multivariate analysis was performed for the predictors of
      fatality. RESULTS: In the second wave of the pandemic, 848 adult patients were
      hospitalized because of suspected influenza, 45 out of 848 (5.3%) died, with 75%
      of fatalities occurring within the first 2 weeks of hospitalization. Among the
      241 laboratory confirmed A(H1N1)pdm09 patients, the case fatality rate was 9%. In
      a multivariate logistic regression model that was performed for the fatalities
      within 14 days after admission, early use of neuraminidase inhibitors was found
      to be protective (Odds ratio: 0.17, confidence interval: 0.03-0.77, p=0.022),
      nosocomial infections (OR: 5.7, CI: 1.84-18, p=0.013), presence of malignant
      disease (OR: 3.8, CI: 0.66-22.01, p=0.133) significantly increased the likelihood
      of fatality. CONCLUSIONS: Early detection of the infection, allowing opportunity
      for the early use of neuraminidase inhibitors, was found to be important for
      prevention of fatality. Nosocomial bacterial infections and underlying malignant
      diseases increased the rate of fatality.

PMID- 24916568
TI  - eWasted time: Redundant work during hospital admission and discharge.
AB  - Potential unintended consequences of health information technology include
      fragmentation of workflow and redundant work. We could not identify any prior
      direct observation studies that quantified redundant work related to health
      information technology in the clinical setting. Our objective was to quantify
      redundant work during admission and discharge to our general internal medicine
      service at an academic medical center. We performed a time and motion study at
      Sunnybrook Health Sciences Centre in Toronto, Canada. We observed 13 clinicians
      performing an admission or a discharge, and the type and length of each task was
      recorded using an Apple iPad tablet. We identified redundant tasks related to
      health information technology and calculated the time spent completing these
      tasks. We found that 22 percent of clinician time was spent on redundant tasks.
      Our finding highlights the importance of workflow and software integration when
      implementing health information technology. 

PMID- 24916569
TI  - Information and decision support needs in patients with type 2 diabetes.
AB  - Diabetes and its sequelae cause a growing burden of morbidity and mortality. For
      many patients living with diabetes, the Internet is an important source of health
      information and support. In the course of the development of an Interactive
      Health Communication Application, combining evidence-based information with
      behavior change and decision support, we assessed the characteristics,
      information, and decision support needs of patients with type 2 diabetes.The
      needs assessment was performed in two steps. First, we conducted semi-structured
      interviews with 10 patients and seven physicians. In the second step, we
      developed a self-assessment questionnaire based on the results of the interviews
      and administered it to a new and larger sample of diabetes patients (N = 178).
      The questionnaire comprised four main sections: (1) Internet use and Internet
      experience, (2) diabetes knowledge, (3) relevant decisions and decision
      preferences, and (4) online health information needs. Descriptive data analyses
      were performed.In the questionnaire study, the patient sample was heterogeneous
      in terms of age, time since diagnosis, and glycemic control. (1) Most
      participants (61.7%) have searched the web for health information at least once.
      The majority (62%) of those who have used the web use it at least once per month.
      (2) Diabetes knowledge was scarce: Only a small percentage (1.9%) of the
      respondents answered all items of the knowledge questionnaire correctly. (3) The
      most relevant treatment decisions concerned glycemic control, oral medication,
      and acute complications. The most difficult treatment decision was whether to
      start insulin treatment. Of the respondents, 69.4 percent thought that medical
      decisions should be made by them and their doctor together. (4) The most
      important information needs concerned sequelae of diabetes, blood glucose
      control, and basic diabetes information.The Internet seems to be a feasible way
      to reach people with type 2 diabetes. The heterogeneity of the sample, especially
      with respect to diabetes knowledge, makes it clear that the projected Interactive
      Health Communication Application should tailor the content to the individual
      user, taking account of individual characteristics and preferences. A wide range
      of topics should be covered. Special attention should be paid to the advantages
      and disadvantages of insulin treatment and the fears and hopes associated with
      it. These results were taken into account when developing the Interactive Health
      Communication Application that is currently being evaluated in a randomized
      controlled trial (International Clinical Trials Registry DRKS00003322). 

PMID- 24916570
TI  - Rapid analysis of three beta-agonist residues in food of animal origin by
      automated on-line solid-phase extraction coupled to liquid chromatography and
      tandem mass spectrometry.
AB  - An automated online solid-phase extraction with liquid chromatography and tandem
      mass spectrometry method was developed and validated for the detection of
      clenbuterol, salbutamol, and ractopamine in food of animal origin. The samples
      from the food matrix were pretreated with an online solid-phase extraction
      cartridge by Oasis MCX for <5 min after acid hydrolysis for 30 min. The peak
      focusing mode was used to elute the target compounds directly onto a C18 column.
      Chromatographic separation was achieved under gradient conditions using a mobile
      phase composed of acetonitrile/0.1% formic acid in aqueous solution. Each analyte
      was detected in two multiple reaction monitoring transitions via an electrospray
      ionization source in a positive mode. The relative standard deviations ranged
      from 2.6 to 10.5%, and recovery was between 76.7 and 107.2% at all quality
      control levels. The limits of quantification of three beta-agonists were in the
      range of 0.024-0.29 MUg/kg in pork, sausage, and milk powder, respectively. This
      newly developed method offers high sensitivity and minimum sample pretreatment
      for the high-throughput analysis of beta-agonist residues. 

PMID- 24916571
TI  - The diplotype Fas -1377A/-670G as a genetic marker to predict a lower risk of
      breast cancer in Chinese women.
AB  - This study was designed to reveal the effects of Fas and FasL polymorphisms of
      interest on breast cancer risk. A total of 439 patients with breast cancer and
      439 controls were enrolled in this study. The genotypes Fas -1377G/A, Fas 
      670A/G, and FasL -844 T/C were detected by MassARRAY. The protein expressions of
      estrogen receptor, progesterone receptor, and CerbB-2 were determined by
      immunohistochemistry. Among the 439 patients, Fas mRNA levels in 22 samples of
      breast cancer and adjacent normal tissues were detected by real-time polymerase
      chain reaction, and the soluble Fas and Fas ligand concentrations of 180 patients
      were measured by enzyme-linked immunosorbent assay. The Fas -1377GA, Fas -1377AA,
      Fas -670AG, Fas -670GG, and FasL -844TC genotypes were associated with a reduced
      risk of breast cancer. Haplotype analysis indicated that Fas -1377G/-670A was
      associated with an increased risk of breast cancer, whereas Fas -1377A/-670A was
      associated with the opposite effect. Furthermore, gene-gene interaction analysis
      revealed that the Fas -1377GA/AA (-670AG/GG) and FasL -844CC or TC/TT genotypes
      were associated with a decreased risk of breast cancer. Meanwhile, -1377GG and 
      670AA genotypes were associated with higher soluble Fas concentrations than other
      genotypes. We conclude that Fas and FasL polymorphisms can affect breast cancer
      risk and that Fas polymorphisms are likely to affect breast cancer risk by
      regulating the soluble Fas concentration.

PMID- 24916572
TI  - Anti-tumor activity of oridonin on SNU-5 subcutaneous xenograft model via
      regulation of c-Met pathway.
AB  - Gastric cancer is the leading cause of cancer death worldwide. Oridonin, a
      diterpenoid isolated from Rabdosia rubescens, has attracted considerable
      attention as a potential treatment for gastric cancer based on its anti-tumor
      effects in many tumor cell lines. However, detailed anti-tumor mechanisms of
      oridonin remain a matter of speculation. In the present study, a gastric
      carcinoma cell line harboring c-Met gene amplification SNU-5 was used to
      investigate the underlying mechanisms. The results showed that in vitro, oridonin
      potently inhibited c-Met phosphorylation and c-Met-dependent cell proliferation
      (IC50 value, 36.8 MUM), meanwhile down-regulated the expression of the downstream
      signaling molecules including phospho-c-Raf, phospho-Erk, and phospho-Akt. In
      vivo, oridonin showed efficacy at well-tolerated doses, including marked
      cytoreductive anti-tumor activity in SNU-5 subcutaneous xenograft model. The anti
      tumor efficacy of oridonin was dose-dependent and showed strong inhibition of c
      Met phosphorylation. Additional mechanism of action studies showed dose-dependent
      inhibition of c-Met-dependent signal transduction, tumor cell proliferation
      (Ki67), and reduction of microvessel density (CD31). These results suggested that
      the anti-tumor activity of oridonin may be mediated by direct effects on tumor
      cell growth or survival as well as anti-angiogenic mechanisms. In summary, the
      results indicated that oridonin exerted anti-tumor growth on human gastric cancer
      SNU-5 in vitro and in vivo by direct regulation of c-Met signaling pathway and
      the anti-tumor effects was mainly based on its anti-proliferation and anti
      angiogenesis.

PMID- 24916573
TI  - The adenocarcinoma cell surface mucin receptor for alpha-fetoprotein: is the same
      receptor present on circulating monocytes and macrophages? A commentary.
AB  - The mucin family of proteins is largely expressed on sedentary epithelial cells
      lining the gastrointestinal, pulmonary, and reproductive tracts and their
      associated organs and malignant tumors. It is less well-known that mucins are
      also expressed on circulatory cells of the immune and inflammatory systems, such
      as monocytes, macrophages, leukemic, and lymphoma cells. The epithelial mucins
      function in (a) protection and lubrication of mucosal linings, (b) cell adhesion
      and cell-to-cell contact, (c) cell migration and metastasis, and (d) signal
      transduction. It would be logical to presume that mucins expressed on circulating
      mononuclear cells could perform similar functions. Recently, it was proposed that
      the alpha-fetoprotein (AFP) receptor, known to be present on solid epithelial
      derived malignant tumor cells, can be identified as a mucin glycoprotein.
      Interestingly, it was also reported that AFP binds to a receptor on circulating
      cells and sedentary tumor cells of lymphoreticular origin, especially monocytes
      associated with lymphomas and leukemias. The primary objective of the present
      commentary is to present literature-based evidence that some of the cell surface
      mucins on sedentary epithelial tumor cells and certain mucins expressed on
      circulating monocytes/macrophages are identical to the AFP receptor. The
      secondary objective is to discuss the role of AFP and its derived peptides in the
      growth suppression of adenocarcinomas and lymphomas using the AFP-mucin receptor
      concept as a key to the mechanism of tumor growth inhibition. 

PMID- 24916574
TI  - Poor citation, coding and reporting: a review of adherence-enhancing
      interventions for highly active antiretroviral therapy creates an inaccurate
      picture of the state of the field.

PMID- 24916575
TI  - Response to letter 'Poor citation, coding and reporting: a review of adherence
      enhancing interventions for highly active antiretroviral therapy creates an
      inaccurate picture of the state of the field'.

PMID- 24916577
TI  - Effective endoscopic diagnosis and treatment of pediatric occult vesicoureteral
      reflux with intermediate to long-term follow-up.
AB  - PURPOSE: Recurrent febrile urinary tract infections (fUTIs) in children with non
      diagnostic voiding cystourethrogram (VCUG) are challenging, as misdiagnosis can
      lead to renal damage and increased morbidity. We compared fUTI rates before and
      after endoscopic treatment of patients with suspected occult VUR. METHODS:
      Between January 2009 and December 2012, children with history of fUTI and non
      diagnostic VCUG(s) underwent endoscopic ureteral hydrodistention (HD) and
      injection of dextranomer hyaluronic acid co-polymer (Dx/HA). fUTI rates before
      and after intervention were evaluated. Demographics, imaging and endoscopic
      findings were assessed. RESULTS: Thirty-four children (mean age 5.4+/-2.8 years)
      underwent bilateral Dx/HA injection for occult VUR. Average follow-up was 28.8
      months. Seventeen children had renal scarring. Mean ureteral HD grade was 2.2/3.
      HD grade for ureters associated with renal scarring was significantly (p<0.05)
      higher (2.6/3) than those without scarring (2.0/3). Mean injected volume was 1.2
      mL. Ureters associated with renal scarring (n=21) required significantly (p<0.05)
      higher volumes (1.4 mL) than those without scarring (n=47; 1.1 mL). Prior to
      intervention, the fUTI rate was 0.15/patient/month compared to just 0.02 after
      treatment (p<0.0001). CONCLUSIONS: Incidence of fUTIs significantly decreased
      following treatment, supporting the use of Dx/HA injection in carefully selected
      children when the suspicion for occult VUR is high.

PMID- 24916576
TI  - Early growth and neurodevelopmental outcome in very preterm infants: impact of
      gender.
AB  - BACKGROUND AND OBJECTIVE: Nutrition in the neonatal unit may impact the
      neurological outcome of very preterm infants, and male preterms are more likely
      to suffer neonatal morbidity and adverse neurological outcomes. We hypothesised
      that growth during hospitalisation would impact neurological outcome differently,
      depending on infant gender. METHODS: Surviving infants born between 1 January
      2003 and 31 December 2009 with a gestational age <33 weeks, and enrolled in Loire
      Infant Follow-up Team, a regional cohort in western France, qualified for the
      study. Growth during neonatal hospitalisation was assessed by the change in
      weight z-score between birth and discharge, and infants where ranked into 5
      classes, depending on their change in z-score (<-2, -2 to -1.01, -1 to -0.51, 
      0.50 to 0.01 and >=0), the last class being the reference. The main outcome
      criterion was neurodevelopmental outcome at 2 years of corrected age. For each
      class of changes in weight z-score, crude or adjusted OR for non-optimal outcome
      was calculated for each gender, and compared between genders. RESULTS: 1221 boys
      and 1056 girls were included. Gender and early growth interact, (p=0.02).
      Moreover when change in weight z-score varied from <-2 to (-0.50 to -0.01),
      adjusted OR for non-optimal outcome varied from 3.2 (1.5-6.8) to 2.2 (1.2-4.1) in
      boys versus 1.8 (0.7-4.2) to 0.95 (0.4-1.9) in girls. For each class, the OR was
      significantly higher in boys. CONCLUSIONS: In very preterm infants, male
      neurodevelopment appears to be much more sensitive than female to poor postnatal
      growth.

PMID- 24916578
TI  - Commentary to "Cumulative incidence of outcomes and urologic procedures after
      augmentation cystoplasty".

PMID- 24916579
TI  - Emergency doctor is struck off over "catalogue of failures".

PMID- 24916580
TI  - A personalized approach to interventional treatment of tricuspid regurgitation:
      experiences from an acute animal study.
AB  - OBJECTIVES: Interventional treatment of tricuspid valve disease has so far
      received little attention due to the anatomical challenges in a thrombogenic
      surrounding. In the present study, we present an imaging-based, personalized
      interventional approach to the therapy of tricuspid regurgitation. METHODS: In
      our porcine model, we used rapid prototyping to build a matrix reproducing the
      geometry of the right atrium that was previously derived from computer tomography
      (CT) scans. Over this matrix, a braided nitinol device fitting almost completely
      the right atrium was crafted. An additional tubular stent component was developed
      to carry a tissue valve prosthesis. This part was designed to be connectable to
      the annular portion of the main device. In our feasibility study, the crimped
      device was implanted via jugular access into the right atrium of 12 pigs and
      expanded subsequently. Following isolated implantation of the device without the
      valve-carrying component, further procedures included implantation of the whole
      composite device, including the mentioned tissue valve. Representing a only
      feasibility study, all implantations were performed under full bypass and direct
      sight. On-site visualization was performed by both echocardiography and
      fluoroscopy. Additional imaging was realized by postoperative CT scans. RESULTS:
      Following implantation, 9 of 12 animals were weaned from cardiopulmonary bypass.
      Correct positioning of the device and orthodromic blood flow as maintained by the
      valve prosthesis were demonstrated by echocardiography and fluoroscopy.
      Postoperative contrast CT evaluation demonstrated proper fitting of the device
      into the right-sided heart cavities without obstruction of the outflow tract.
      Autopsy additionally confirmed its correct positioning without major trauma to
      surrounding structures. CONCLUSIONS: We demonstrated the feasibility in principle
      of a personalized interventional treatment for tricuspid regurgitation using a
      braided stent, based on individual cardiac imaging, with anchoring forces mainly
      exerted on the venae cavae and on the inner surface of the right atrium. The
      design process of this device is a good indicator of the growing potential of an
      imaging-based personalized simulation and production approach for the treatment
      of tricuspid valve disease.

PMID- 24916581
TI  - Use of a fast-track surgery protocol on patients undergoing minimally invasive
      oesophagectomy: preliminary results.
AB  - OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of
      a fast-track surgery (FTS) protocol on patients undergoing minimally invasive
      oesophagectomy. METHODS: We retrospectively analysed the clinical data of 80
      eligible patients who underwent elective minimally invasive oesophagectomy in our
      department from January 2012 to April 2013 by the same surgical team. Two groups
      of these patients were compared. The control group comprised patients treated
      with traditional methods. Clinical parameters were compared. The study group was
      formed by patients treated with the fast-track concept, such as (i) a semi-liquid
      meal was administered up to 6 h before surgery and the patients were made to
      drink 200 ml of 10% glucose solution 3 h before surgery; (ii) no nasogastric
      tube, no abdominal drainage tube and no draining sinus in the neck; (iii) the
      chest tube and catheter were removed as early as possible; (iv) prevention of
      hypothermia therapy; (v) an attempt at bedside rehabilitation on postoperative
      day (POD) 2; and (vi) early postoperative enteral nutrition, restrictive
      intravenous fluids intraoperatively and postoperatively, and oral feeding
      initiated 48 h after surgery. RESULTS: There were no significant differences
      between the two groups with regard to age, sex, pathologic tumor-node-metastasis
      stage, tumour location, pathology, American Society of Anesthesiologists score,
      preoperative albumin level, 30-day readmission or complications (P >0.05).
      Compared with the conventional group, the FTS group had earlier first flatus [(3
      (3-4) vs 6 (6-7) days], less fluid transfusion [2.1 (2.06-2.2) vs 2.8 (2.7-2.9)
      l] and shorter postoperative hospital stay [7 (6-9) days vs 12 (10-16.5) days] (P
      <0.05). There was no difference between the two groups with regard to vomiting,
      but patients in the conventional group suffered from/experienced pharyngitis
      considerably more than the FTS group (P <0.001). CONCLUSIONS: FTS on patients
      with oesophageal cancer receiving minimally invasive oesophagectomy is safe,
      feasible and efficient, and can accelerate postoperative rehabilitation. Compared
      with the conventional protocol, its advantages were limited to short-term follow
      up.

PMID- 24916582
TI  - Saturated and trans fats and dementia: a systematic review.
AB  - Cognitive disorders of later life are potentially devastating. To estimate the
      relationship between saturated and trans fat intake and risk of cognitive
      disorders. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials
      were searched for studies reporting saturated or trans fat intake and incident
      dementia, Alzheimer's disease (AD), or mild cognitive impairment (MCI) or
      cognitive decline. Only observational studies met the inclusion criteria: 4 for
      AD or other dementias, 4 for MCI, and 4 for cognitive decline. Saturated fat
      intake was positively associated with AD risk in 3 of 4 studies, whereas the
      fourth suggested an inverse relationship. Saturated fat intake was also
      positively associated with total dementia in 1 of 2 studies, with MCI in 1 of 4
      studies, and with cognitive decline in 2 of 4 studies. Relationships between
      trans fat intake and dementia were examined in 3 reports with mixed results.
      Several, although not all, prospective studies indicate relationships between
      saturated and trans fat intake and risk of cognitive disorders. 

PMID- 24916584
TI  - Adenomas of the ampulla of Vater: a comparison of outcomes of operative and
      endoscopic resections.
AB  - BACKGROUND: Data comparing operative and endoscopic resection of adenomas of the
      ampulla of Vater are limited. Our aims were to evaluate and compare the long-term
      results and outcomes of endoscopic and operative resections of benign tumors of
      the ampulla of Vater as well as to determine which features of benign
      periampullary neoplasms would predict recurrence or failure of endoscopic therapy
      and therefore need for operative treatment. METHODS: Retrospective review of all
      patients treated for adenomas of ampulla of Vater at our institution from 1994 to
      2009. RESULTS: Over a 15-year span, 180 patients (mean age 59 years) were treated
      for benign adenomas of the ampulla of Vater with a mean follow-up of 4.4 years.
      Obstructive jaundice was more common in the operative resection group (p =
      0.006). The adenomas were tubular in 83 patients (44%), tubulovillous in 77 (45%)
      and villous in 20 (11%). Endoscopic resection alone was performed in 130 patients
      (78%). Operative resection was performed in 50 patients (28%), with
      pancreatoduodenectomy in 40, transduodenal local resection in 9, and pancreas
      sparing total duodenectomy in 1. Nine patients who underwent endoscopic resection
      initially were endoscopic treatment failures. Fifty-eight percent of
      endoscopically treated patients required one endoscopic resection, while 58 (42%)
      required two or more endoscopic resections (range 2-8). Patients who underwent
      operative resection had larger tumors with a mean size of 3.7 +/- 2.8 versus 1.8
      +/- 1.5 cm in those treated by endoscopic resection (p < 0.001) or intraductal
      extension (p = 0.02). Intraductal extension and ulceration had no effect on
      recurrence if completely resected endoscopically (p = 0.41 and p = 0.98,
      respectively). Postoperative complications occurred in 58% of patients, and post
      endoscopic complications in 29% (p < 0.001). Endoscopic resection was associated
      with a greater than fivefold risk of recurrence than operative resection (p =
      0.006); 4% of recurrences had invasive carcinomas. When comparing patients who
      underwent local resections only (endoscopic and operative), there was no
      difference in the recurrence rate between endoscopic resection and operative
      transduodenal resection (32 versus 33%; p = 0.49). The need for two or more
      endoscopic resections for complete tumor removal was associated with 13-fold
      greater risk of recurrence (p < 0.001). CONCLUSION: There is no significant
      difference between endoscopic and local operative resections of benign adenomas
      of ampulla of Vater; recurrences are more common when two or more endoscopic
      resections are required for complete tumor removal. Appropriate adenomas for
      endoscopic resection included tumors <3.6 cm that do not extend far enough
      intraductally (on EUS) to preclude an endoscopic snare ampullectomy.

PMID- 24916585
TI  - Prosthetic graft for superior mesenteric-portal vein reconstruction in
      pancreaticoduodenectomy: a retrospective, multicenter study.
AB  - BACKGROUND: The use of prosthetic grafts for superior mesenteric-portal vein
      reconstruction (SMPVR) after pancreaticoduodenectomy (PD) with venous resection
      remains controversial. We evaluated the effectiveness and safety of using
      polytetrafluoroethylene (PTFE) interposition grafts for SMPVR after PD. METHODS:
      We identified 76 patients who underwent PD with segmental vein resection for
      pancreatic head and periampullary neoplasms at three centers between January 2007
      and June 2012. The venous reconstruction technique depended on the length of
      venous involvement. Forty-two and 34 patients underwent SMPVR with primary
      anastomosis and SMPVR with PTFE interposition grafts, respectively. The
      postoperative morbidity, mortality, and patency were compared. For the patients
      with pancreatic ductal adenocarcinoma (n = 65), survival was compared between the
      SMPVR with primary anastomosis (n = 36) and SMPVR with PTFE interposition graft
      groups (n = 29). RESULTS: Patients undergoing SMPVR with PTFE grafts had larger
      tumor sizes (3.4 +/- 0.9 cm, 2.9 +/- 0.9 cm, P = 0.016), longer operative
      durations (492.9 +/- 107.5 min, 408.8 +/- 78.8 min, P < 0.001), and greater blood
      loss (986.8 +/- 884.5 ml, 616.7 +/- 485.5 ml, P = 0.040) compared to those
      undergoing SMPVR with primary anastomosis. However, 30-day postoperative
      morbidity and mortality did not differ (29.4 and 2.9 %, respectively, for PTFE
      grafts and 33.3 and 7.1 %, respectively, for primary anastomosis). There were no
      cases of graft infection. The estimated cumulative patency of SMPVR 6 and 12
      months after surgery did not differ (87.9 and 83.5 % after PTFE grafts,
      respectively, and 94.4 and 86.4 % after primary anastomosis, respectively). For
      patients who underwent surgery for pancreatic ductal adenocarcinoma, there were
      no significant differences in the median survival time (11 vs. 12 months) or the
      1-, 2-, and 3-year survival rates (35.7, 12.5, and 4.2 vs. 36.4, 17.3, and 8.7 %,
      respectively) for the PTFE and primary anastomosis groups. CONCLUSIONS: PTFE
      grafts could provide a safe and effective option for venous reconstruction after
      PD in patients with segmental vein resection.

PMID- 24916587
TI  - Effectiveness of intraoperative cholangiography using indocyanine green (versus
      contrast fluid) for the correct assessment of extrahepatic bile ducts during day
      case laparoscopic cholecystectomy.
AB  - INTRODUCTION: During cholecystectomy, intraoperative cholangiography using
      contrast fluid (IOC-CF) is still the "gold standard" for biliary tract
      identification but has many associated pitfalls. A new IOC technique using
      indocyanine green (IOC-IG) appears to be promising. Here, we studied the
      effectiveness of IOC-IG (vs IOC-CF) during day-case laparoscopic cholecystectomy.
      MATERIALS AND METHODS: Over a 6-month period, we included 23 patients (with no
      cirrhosis or risk factors for choledocholithiasis) scheduled for day-case
      laparoscopic cholecystectomy. The primary efficacy criterion was the
      "analyzability rate" (i.e., the ability to identify the cystic duct, the cystic
      duct-hepatic duct junction, and the common bile duct) for the IOC-CF and IOC-IG
      procedures after dissection. Indocyanine green was infused under general
      anesthesia. The same near-infrared laparoscopic imaging system was used for IOC
      IG and conventional visual inspection. IOC-CF was always attempted after
      dissection. Each patient served as his/her own control. Cholecystectomies were
      video-recorded for subsequent off-line, blind analysis. RESULTS: The
      analyzability rate was 74 % for IOC-IG after dissection, 70 % for IOC-CF (p =
      0.03), 26 % for conventional visual inspection, and 48 % for IOC-IG before
      dissection. When each IOC modality (conventional visual inspection, IOC-IG before
      and after dissection) was considered as a diagnostic test, the accuracy for
      simultaneous identification of the three anatomic elements was respectively 48,
      52, and 74 %. No adverse events occurred during the IOC-IG procedure. CONCLUSION:
      IOC-IG was feasible and safe. Our results suggest that this technique is more
      effective than IOC-CF for biliary tract identification after dissection and may
      constitute a powerful diagnostic test for the detection of extrahepatic ducts.

PMID- 24916588
TI  - NSAID use and colorectal anastomotic leaks. Caution and further investigation.

PMID- 24916589
TI  - Thrombin mediates vagal apoptosis and dysfunction in inflammatory bowel disease.
AB  - BACKGROUND: In inflammatory bowel disease, autonomic dysfunction contributes to
      symptoms, morbidity, and health care resource utilization. Efferent vagal
      neurons, which provide the primary parasympathetic input to the gastrointestinal
      tract, are housed in the dorsal motor nucleus of the vagus (DMV) in the
      brainstem. This study seeks to characterize the effects of IBD on DMV neuronal
      survival and function. METHODS: TNBS (picrylsulfonic acid) was administered by
      enema to induce colitis in rats. Brain sections through the DMV were examined for
      neuronal apoptosis using TUNEL labeling, and for glial cell activation by
      immunofluorescence. Prothrombin production was evaluated via quantitative RT-PCR
      from DMV tissue, as well as by double immunofluorescence in DMV sections. To
      investigate the effects of thrombin in the DMV, thrombin or thrombin and an
      antagonist to its receptor were administered into the fourth ventricle via a
      stereotactically placed cannula. DMV sections were then examined for apoptosis by
      TUNEL assay. To evaluate the effect of thrombin on DMV neuronal function, we
      examined calcium signaling in primary DMV neuron cultures following exposure to
      thrombin and other neurotransmitters. RESULTS: TNBS colitis is associated with
      significantly increased rates of DMV neuronal apoptosis, affecting 12.7 % of DMV
      neurons in animals with colitis, compared to 3.4 % in controls. There was a
      corresponding increase in DMV neuron activated caspase-3 immunoreactivity (14.8
      vs. 2.6 % of DMV neurons). TNBS-treated animals also demonstrated significantly
      increased DMV astrocyte and microglial immunoreactivity, indicating glial cell
      activation. DMV prothrombin production was significantly increased in TNBS
      colitis, with a close anatomic relationship between prothrombin and microglia.
      Direct DMV exposure to thrombin replicated the apoptosis and activation of
      caspase-3 seen in TNBS colitis; these effects were prevented by coadministration
      of the PAR-1 inhibitor FR171113. Cultured DMV neurons exhibited impaired calcium
      signaling in response to neurotransmitters following exposure to thrombin.
      Glutamate-induced calcium transients decreased by 59 %, and those triggered by
      GABA were reduced by 61 %. PAR-1 antagonism prevented these thrombin-induced
      changes in calcium signaling. CONCLUSIONS: IBD is associated with DMV microglial
      activation and production of prothrombin. Thrombin in the DMV causes vagal neuron
      apoptosis and decreased sensitivity to neurotransmitters.

PMID- 24916591
TI  - Incomplete circle of willis and migraine: role for shear-induced platelet
      aggregation?

PMID- 24916590
TI  - Nodal counts and lymph node ratio impact survival after distal pancreatectomy for
      pancreatic adenocarcinoma.
AB  - BACKGROUND: The number of lymph nodes required for accurate staging after distal
      pancreatectomy for pancreatic adenocarcinoma is unknown. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) database was used to identify
      1,473 patients who underwent distal pancreatectomy for pancreatic adenocarcinoma
      from 1998 to 2010. We evaluated the influence of the total number of lymph nodes
      examined (NNE) and the lymph node ratio (LNR-positive nodes/total nodes examined)
      on survival. RESULTS: The median NNE was 8. No nodes were examined in 232 (16%)
      of the patients, and 843 (57%) had <10 NNE. Of the patients who had at least one
      node examined, 612 (49%) were node positive. In the node-negative subset, the
      median and 5-year overall survival for patients with <=10 NNE was significantly
      worse than patients with >10 NNE (16 vs. 20 months and 13 vs. 19%, respectively,
      p < 0.011). For node-positive patients, those with LNR <=0.1 had better 5-year
      overall survival compared with LNR >0.1 (17 vs. 6%, p = 0.002). DISCUSSION:
      Patients with pancreatic cancer undergoing distal pancreatectomy should ideally
      have at least 11 lymph nodes examined to avoid understaging. For node-positive
      patients, LNR may be a better prognostic indicator than the total number of
      positive nodes.

PMID- 24916592
TI  - Orthostatic headache without intracranial hypotension: a headache due to
      psychiatric disorder?

PMID- 24916593
TI  - Perceived body weight status of youngsters interferes with headache in obese and
      non-obese subjects.

PMID- 24916594
TI  - Perceived body weight status of youngsters interferes with headache in obese and
      non-obese subjects: a response.

PMID- 24916595
TI  - A discussion of "critical evaluation of migraine trigger site decompression
      surgery".

PMID- 24916596
TI  - Acute postpartum headache.

PMID- 24916597
TI  - Editorial: complementary and Alternative Medicine (CAM), Ayurvedic medicine, and
      research into behavioral and mind/body interventions in headache.

PMID- 24916598
TI  - Aura with headache.

PMID- 24916599
TI  - [Aura with a headache (cafaleia)].

PMID- 24916600
TI  - Persistence of Parvovirus B19 (B19V) DNA and humoral immune response in B19V
      infected blood donors.
AB  - BACKGROUND AND OBJECTIVES: Parvovirus B19 (B19V) DNA seems to persist in the
      plasma of B19V-infected blood donors. The relevance of this for recipients of
      single-donor blood components is yet unclear. MATERIAL AND METHODS: We studied
      serial archive and follow-up samples from 75 B19V-infected blood donors to obtain
      more data about the duration and degree of viraemia and the presence of IgG and
      IgM anti-B19V. IgG antibodies were further characterized by Western blot analysis
      in 29 donors. RESULTS: In 411 B19V DNA-positive samples collected, we found high
      concentrations (>10(6) IU B19V DNA/ml plasma) in five. B19V DNA persisted for a
      mean of 21.5 months (range: 2.3-52.4; 95% confidence interval, 19.1-23.9 months)
      in all donors. Only 15 such samples had either no or low-titre IgG anti-B19V. IgG
      antibodies were predominantly directed against epitopes on the minor capsid
      protein VP1, thus probably of neutralizing type with high avidity. IgM anti-B19V
      was detectable in 9/13 samples with high DNA concentrations. CONCLUSIONS: The
      vast majority of single-donor blood components with detectable B19V DNA are
      probably not infectious for their recipients because DNA is at only low levels
      and the donors also have potentially neutralizing antibodies with high avidity.
      Anti-B19V IgM testing does not identify every donation with high B19V DNA
      concentrations, but, in addition to B19V NAT testing, donors with persistent IgG
      anti-B19V might be considered 'B19V-safe' for single-donor blood components.

PMID- 24916601
TI  - The use of lysozyme modified with fluorescein for the detection of Gram-positive
      bacteria.
AB  - Lysozyme (1,4-beta-N-acetylmuramidase) is commonly applied in the food, medical,
      and pharmaceutical industries. In this study, we tested a novel application of
      fluorescein-modified lysozyme (using carboxyfluorescein with a triazine-based
      coupling reagent) as a new tool for the detection of Gram-positive soil bacteria.
      The results, obtained by cultivation methods, fluorescence analysis, and laser
      interferometry, showed that, after optimization, fluorescein-modified lysozyme
      could be used to evaluate the prevalence of Gram-positive bacteria essential in
      bioremediation of soils with low pH, such as those degraded by sulfur. 

PMID- 24916602
TI  - Processing of nociceptive input from posterior to anterior insula in humans.
AB  - Previous brain imaging studies have shown robust activations in the insula during
      nociceptive stimulation. Most activations involve the posterior insular cortex
      but they can cover all insular gyri in some fMRI studies. However, little is
      known about the timing of activations across the different insular sub-regions.
      We report on the distribution of intracerebrally recorded nociceptive laser
      evoked potentials (LEPs) acquired from the full extent of the insula in 44
      epileptic patients. Our study shows that both posterior and anterior subdivisions
      of the insular cortex respond to a nociceptive heat stimulus within a 200-400 ms
      latency range. This nociceptive cortical potential occurs firstly, and is larger,
      in the posterior granular insular cortex. The presence of phase reversals in LEP
      components in both posterior and anterior insular regions suggests activation of
      distinct, presumably functionally separate, sources in the posterior and anterior
      parts of the insula. Our results suggest that nociceptive input is first
      processed in the posterior insula, where it is known to be coded in terms of
      intensity and anatomical location, and then conveyed to the anterior insula,
      where the emotional reaction to pain is elaborated.

PMID- 24916603
TI  - Spore germination and germinant receptor genes in wild strains of Bacillus
      subtilis.
AB  - AIMS: To compare the germination of laboratory and wild strains of Bacillus
      subtilis. METHODS AND RESULTS: The spore germination of B. subtilis 168 (subsp.
      subtilis) was compared with that of the laboratory strain W23 (subsp. spizizenii)
      and desert-sourced isolates, including one member of subsp. subtilis (RO-NN-1),
      strains TU-B-10, RO-E-2, N10 and DV1-B-1, (all subsp. spizizenii), the B.
      mojavensis strain RO-H-1 and a B. subtilis natto strain. All germinated in L
      alanine, although some were slower, and some 10-fold less sensitive to germinant.
      All germinated in calcium dipicolinate (CaDPA). Germination in asparagine,
      glucose, fructose + KCl was slow and incomplete in many of the strains, and
      decoating RO-NN-1 and W23 spores did not restore germination rates. Comparing the
      sequences of B. subtilis strains 168, RO-NN-1, W23, TU-B-10 and DV1-B-1, the
      operons encoding GerA, B and K germinant receptors were intact, although the two
      additional operons yndDEF and yfkQRST had suffered deletions or were absent in
      several spizizenii strains. CONCLUSIONS: Wild strains possess an efficient
      germination machinery for L-alanine germination. AGFK germination is often less
      efficient, the gerB genes more diverged, and the two germinant receptor operons
      of unknown function have been lost from the genome in many subsp. spizizenii
      strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The two major subspecies of B.
      subtilis have conserved GerA receptor function, confirming its importance, at
      least in the natural environments of these strains.

PMID- 24916604
TI  - Patterns of knee osteoarthritis in a hospital setting in sub-Saharan Africa.
AB  - Osteoarthritis (OA), the most prevalent joint disease in adults, ranks among the
      top 5 causes of disability. The burden of OA is expected to be greater in
      developing countries, where life expectancy is increasing and access to joint
      replacement therapy is not readily available. Risk factors associated with knee
      OA in Africa may differ from those identified in other parts of the world. This
      study aimed to establish the prevalence, clinical presentation, and associated
      factors of knee OA in two large referral centers in Cameroon. Between February
      and July 2012, we performed a cross-sectional analysis of 148 patients with knee
      OA followed at two rheumatology units in Douala. We included all patients with
      mechanical knee pain, who fulfilled the 1986 ACR for the classification and
      reporting of knee OA. One thousand four hundred ninety-six patients with
      musculoskeletal complaints were seen; 148 (9.9%) with knee OA were analyzed. Mean
      age was 56.9 +/- 10.7 years, 75% were females, and 68% were post-menopausal. The
      VAS of pain at the time of diagnosis was higher than 50/100 mm in 64.2% of
      patients. Mean pain duration was 1 year (7 months-3.5 years). Obesity (BMI > 30)
      was present in 52% of patients, hypertension in 37.2%, and diabetes in 8.8%. Knee
      x-ray showed 35.5% of patients with grades III and IV on Kellgren and Lawrence
      classification. Bilateral bi-compartmental knee OA was found in 38.5% of patients
      and bilateral tricompartmental in 14.2%. The mean Lequesne disability index (LDI)
      was 8.4 +/- 2.8. Pain intensity did not correlate with radiological findings
      whereas there was an association between pain and LDI. Knee OA is not rare among
      patients in Cameroon. Multiple factors including limited access to health care
      may account for why knee OA patients present at later stages of the disease with
      severe disability.

PMID- 24916605
TI  - The association of comorbid conditions with patient-reported outcomes in Veterans
      with hip and knee osteoarthritis.
AB  - There is limited understanding of how comorbid health conditions affect
      osteoarthritis (OA)-related outcomes. This study examined associations of
      different comorbidity measures with baseline OA-related patient-reported outcomes
      (PROs) among patients with hip and knee OA. Data were from patients (N = 300, 9 %
      female, mean age = 61.1; SD = 9.2) enrolled in a randomized control trial at the
      Durham Veterans Affairs Medical Center. Separate multivariable regression models,
      adjusted for demographic and clinical characteristics, examined the association
      of each comorbidity measure with baseline PROs: pain, physical function,
      depressive symptoms, fatigue, and insomnia. Comorbidity measures included the
      Self-Administered Comorbidity Questionnaire (SACQ), conditions reported as
      activity-limiting (SACQ-AL), and indicators of depression, diabetes,
      hypertension, and back pain. Mean (SD) numbers of comorbid conditions and
      activity-limiting conditions were 3.4 (1.8) and 1.6 (1.4), respectively.
      Comorbidity scores (SACQ overall and SACQ-AL) and individual comorbidity
      conditions were each associated with worse OA-related PROs adjusting for
      demographic and clinical factors. Worse SACQ overall and SACQ-AL scores were
      associated with worse mean scores for pain, depressive symptoms, fatigue, and
      insomnia (p values <0.01). Additionally, increasing SACQ-AL scores were
      associated with worse mean scores for function (p < 0.01). Depression was
      associated with worse pain (p = 0.03), fatigue, and insomnia (p values <0.01).
      Diabetes was associated with worse fatigue (p = 0.01), depressive symptoms (p =
      0.02), and insomnia (p = 0.03). Back pain was associated with worse pain scores
      (p = 0.02). Results provide evidence that comorbidity burden, particularly
      activity-limiting conditions, is associated with worse OA-related PROs.
      Interventions for patients with OA need to address comorbid conditions and their
      impact on key outcomes.

PMID- 24916606
TI  - Methotrexate for treating rheumatoid arthritis.
AB  - BACKGROUND: Methotrexate is a folic acid antagonist widely used for the treatment
      of neoplastic disorders. Methotrexate inhibits the synthesis of deoxyribonucleic
      acid (DNA), ribonucleic acid (RNA) and proteins by binding to dihydrofolate
      reductase. Currently, methotrexate is among the most commonly used drugs for the
      treatment of rheumatoid arthritis (RA). This is an update of the previous
      Cochrane systematic review published in 1997. OBJECTIVES: To evaluate short term
      benefits and harms of methotrexate for treating RA compared to placebo. SEARCH
      METHODS: The Cochrane Musculoskeletal Group Trials Register, The Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched from
      1966 to 1997 and then updated to November 2013. The search was complemented with
      a bibliography search of the reference lists of trials retrieved from the
      electronic search. SELECTION CRITERIA: Randomized controlled trials and
      controlled clinical trials comparing methotrexate (MTX) monotherapy against
      placebo alone in people with RA. Any trial duration and MTX doses were included.
      DATA COLLECTION AND ANALYSIS: Two review authors independently determined which
      studies were eligible for inclusion, extracted data and assessed risk of bias.
      Outcomes were pooled using mean differences (MDs) for continuous variables or
      standardized mean differences (SMDs) when different scales were used to measure
      the same outcome. Pooled risk ratio (RR) was used for dichotomous variables.
      Fixed-effect models were used throughout, although random-effects models were
      used for outcomes showing heterogeneity. MAIN RESULTS: Five trials with 300
      patients were included in the original version of the review. An additional two
      trials with 432 patients were added to the 2013 update of the review for a total
      of 732 participants. The trials were generally of unclear to low risk of bias
      with a follow-up duration ranging from 12 to 52 weeks. All trials included
      patients who have failed prior treatment (for example, gold therapy, D
      penicillamine, azathioprine or anti-malarials); mean disease duration that ranged
      between 1 and 14 years with six trials reporting more than 4 years; and weekly
      doses that ranged between 5 mg and 25 mg. BENEFITS: Statistically significant and
      clinically important differences were observed for most efficacy outcomes. MTX
      monotherapy showed a clinically important and statistically significant
      improvement in the American College of Rheumatology (ACR) 50 response rate when
      compared with placebo at 52 weeks (RR 3.0, 95% confidence interval (CI) 1.5 to
      6.0; number needed to treat (NNT) 7, 95% CI 4 to 22). Fifteen more patients out
      of 100 had a major improvement in the ACR 50 outcome compared to placebo
      (absolute treatment benefit (ATB) 15%, 95% CI 8% to 23%).Statistically
      significant improvement in physical function (scale of 0 to 3) was also observed
      in patients receiving MTX alone compared with placebo at 12 to 52 weeks (MD 
      0.27, 95% CI -0.39 to -0.16; odds ratio (OR) 2.8, 95% CI 0.23 to 32.2; NNT 4, 95%
      CI 3 to 7). Nine more patients out of 100 improved in physical function compared
      to placebo (ATB -9%, 95% CI -13% to -5.3%). Similarly, the proportion of patients
      who improved at least 20% on the Short Form-36 (SF-36) physical component was
      higher in the MTX-treated group compared with placebo at 52 weeks (RR 1.5, 95% CI
      1.0 to 2.1; NNT 9, 95% CI 4 to 539). Twelve more patients out of 100 showed an
      improvement of at least 20% in the physical component of the quality of life
      measure compared to placebo (ATB 12%, 95% CI 1% to 24%). No clinically important
      or statistically significant differences were observed in the SF-36 mental
      component.Although no statistically significant differences were observed in
      radiographic scores (that is, Total Sharp score, erosion score, joint space
      narrowing), radiographic progression rates (measured by an increase in erosion
      scores of more than 3 units on a scale ranging from 0 to 448) were statistically
      significantly lower for patients in the MTX group compared with placebo-treated
      patients (RR 0.31, 95% CI 0.11 to 0.86; NNT 13, 95% CI 10 to 60). Eight more
      patients out of 100 showed less damage to joints measured by an increase in
      erosion scores compared to placebo (ATB -8%, 95% CI -16% to -1%). In the one
      study measuring remission, no participants in either group met the remission
      criteria. These are defined by at least five of (>= 2 months): morning stiffness
      of < 15 minutes, no fatigue, no joint pain by history, no joint tenderness, no
      joint swelling, and Westergren erythrocyte sedimentation rate (ESR) of < 20 mm/hr
      in men and < 30 mm/hr in women. HARMS: Patients in the MTX monotherapy group were
      twice as likely to discontinue from the study due to adverse events compared to
      patients in the placebo group, at 12 to 52 weeks (16% versus 8%; RR 2.1, 95% CI
      1.3 to 3.3; NNT 13, 95% CI 6 to 44). Compared to placebo, nine more people out of
      100 who took MTX withdrew from the studies because of side effects (ATB 9%, 95%
      CI 3% to 14%). Total adverse event rates at 12 weeks were higher in the MTX
      monotherapy group compared to the placebo group (45% versus 15%; RR 3.0, 95% CI
      1.4 to 6.4; NNT 4, 95% CI 2 to 17). Thirty more people out of 100 who took MTX
      compared to those who took placebo experienced any type of side effect (common or
      rare) (ATB 30, 95% CI 13% to 47%). No statistically significant differences were
      observed in the total number of serious adverse events between the MTX group and
      the placebo group at 27 to 52 weeks. Three people out of 100 who took MTX alone
      experienced rare but serious side effects compared to 2 people out of 100 who
      took a placebo (3% versus 2%, respectively). AUTHORS' CONCLUSIONS: Based on
      mainly moderate to high quality evidence, methotrexate (weekly doses ranging
      between 5 mg and 25 mg) showed a substantial clinical and statistically
      significant benefit compared to placebo in the short term treatment (12 to 52
      weeks) of people with RA, although its use was associated with a 16%
      discontinuation rate due to adverse events.

PMID- 24916607
TI  - Molecular simulations of beta-lactoglobulin complexed with fatty acids reveal the
      structural basis of ligand affinity to internal and possible external binding
      sites.
AB  - The interaction of saturated fatty acids of different length (C8:0 to C18:0) with
      beta-lactoglobulin (betaLG) was investigated by molecular dynamics simulation and
      docking approaches. The results show that the presence of such ligands in the
      hydrophobic central cavity of betaLG, known as the protein calyx, determines an
      enhancement of atomic fluctuations compared with the unliganded form, especially
      for loops at the entrance of the binding site. Concerted motions are evidenced
      for protein regions that could favor the binding of ligands. The mechanism of
      anchoring of fatty acids of different length is similar for the carboxylate head
      group, through electrostatic interactions with the side chains of Lys60/Lys69.
      The key protein residues to secure the hydrocarbon chain are Phe105/Met107, which
      adapt their conformation upon ligand binding. In particular, Phe105 provides an
      additional hydrophobic clamp only for the tail of the two fatty acids with the
      longest chains, palmitic, and stearic acid, which are known to bind betaLG with a
      high affinity. The search of additional external binding sites for fatty acids,
      distinct from the calyx, was also carried out for palmitic acid. Two external
      sites with a lower affinity were identified as secondary sites, one consisting in
      a hydrophobic cavity allowing two distinct binding modes for the fatty acid, and
      the other corresponding to a surface crevice close to the protein alpha-helix.
      The overall results provide a comprehensive picture of the dynamical behavior of
      betaLG in complex with fatty acids, and elucidate the structural basis of the
      binding of these physiological ligands.

PMID- 24916608
TI  - An integrative view of school functioning: transactions between self-regulation,
      school engagement, and teacher-child relationship quality.
AB  - This study investigates the dynamic interplay between teacher-child relationship
      quality and children's behaviors across kindergarten and first grade to predict
      academic competence in first grade. Using a sample of 338 ethnically diverse 5
      year-old children, nested path analytic models were conducted to examine
      bidirectional pathways between children's behaviors and teacher-child
      relationship quality. Low self-regulation in kindergarten fall, as indexed by
      inattention and impulsive behaviors, predicted more conflict with teachers in
      kindergarten spring and this effect persisted into first grade. Conflict and low
      self-regulation jointly predicted decreases in school engagement which in turn
      predicted first-grade academic competence. Findings illustrate the importance of
      considering transactions between self-regulation, teacher-child relationship
      quality, and school engagement in predicting academic competence. 

PMID- 24916609
TI  - Relationships between lead biomarkers and diurnal salivary cortisol indices in
      pregnant women from Mexico City: a cross-sectional study.
AB  - BACKGROUND: Lead (Pb) exposure during pregnancy may increase the risk of adverse
      maternal, infant, or childhood health outcomes by interfering with hypothalamic
      pituitary-adrenal-axis function. We examined relationships between maternal blood
      or bone Pb concentrations and features of diurnal cortisol profiles in 936
      pregnant women from Mexico City. METHODS: From 2007-11 we recruited women from
      hospitals/clinics affiliated with the Mexican Social Security System. Pb was
      measured in blood (BPb) during the second trimester and in mothers' tibia and
      patella 1-month postpartum. We characterized maternal HPA-axis function using 10
      timed salivary cortisol measurements collected over 2-days (mean: 19.7, range: 14
      35 weeks gestation). We used linear mixed models to examine the relationship
      between Pb biomarkers and cortisol area under the curve (AUC), awakening response
      (CAR), and diurnal slope. RESULTS: After adjustment for confounders, women in the
      highest quintile of BPb concentrations had a reduced CAR (Ratio: -13%; Confidence
      Interval [CI]: -24, 1, p-value for trend < 0.05) compared to women in the lowest
      quintile. Tibia/patella Pb concentrations were not associated with CAR, but
      diurnal cortisol slopes were suggestively flatter among women in the highest
      patella Pb quantile compared to women in the lowest quantile (Ratio: 14%; CI: -2,
      33). BPb and bone Pb concentrations were not associated with cortisol AUC.
      CONCLUSIONS: Concurrent blood Pb levels were associated with cortisol awakening
      response in these pregnant women and this might explain adverse health outcomes
      associated with Pb. Further research is needed to confirm these results and
      determine if other environmental chemicals disrupt hypothalamic-pituitary-adrenal
      axis function during pregnancy.

PMID- 24916610
TI  - Roles of miRNAs in regulating the differentiation and maturation of myeloid
      derived suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and
      play an essential role in tumor-associated immunosuppression, which hampers
      effective immunotherapeutic approaches. MicroRNAs (miRNAs) are short noncoding
      RNAs that negatively regulate target gene expression at the posttranscriptional
      level. miRNAs are involved in regulating cell proliferation, differentiation and
      maturation, and abnormal expression and function of miRNAs are recognized in
      various human diseases. Accumulating evidence shows that various miRNAs modulate
      the development and differentiation of myeloid cells, which implies their
      possible role in the differentiation of MDSCs into mature myeloid cells. Our
      recent studies have found that the classical myeloid differentiation related gene
      runt-related transcription factor 1 (Runx1) and target nuclear factor 1/A (NFI-A)
      are modulated during the differentiation and maturation of MDSCs while six miRNAs
      are found to possibly regulate these two targets by miRNA array analysis. Thus,
      we hypothesize that the predicted miRNAs may modulate the target genes to
      regulate the differentiation and maturation of MDSCs. Further studies will
      provide a novel potential approach for tumor immunotherapy. 

PMID- 24916611
TI  - Extranodal Rosai-Dorfman disease involving the right atrium in a 60-year-old
      male.
AB  - Rosai-Dorfman disease (RDD) involving the cardiovascular system is extremely
      rare; to our knowledge, there are only 9 cases in the literature. Here, a case of
      a 60-year-old male with RDD involving the right atrium is presented. A
      comprehensive literature review was undertaken to summarize the clinical and
      pathologic features of this disorder. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2143194139120169.

PMID- 24916613
TI  - A third of adults in England have "prediabetes," study says.

PMID- 24916612
TI  - The effect of mechanical loading on osteogenesis of human dental pulp stromal
      cells in a novel in vitro model.
AB  - Tooth loss often results in alveolar bone resorption because of lack of
      mechanical stimulation. Thus, the mechanism of mechanical loading on stem cell
      osteogenesis is crucial for alveolar bone regeneration. We have investigated the
      effect of mechanical loading on osteogenesis in human dental pulp stromal cells
      (hDPSCs) in a novel in vitro model. Briefly, 1 * 10(7) hDPSCs were seeded into 1
      ml 3% agarose gel in a 48-well-plate. A loading tube was then placed in the
      middle of the gel to mimic tooth-chewing movement (1 Hz, 3 * 30 min per day, n =
      3). A non-loading group was used as a control. At various time points, the
      distribution of live/dead cells within the gel was confirmed by fluorescence
      markers and confocal microscopy. The correlation and interaction between the
      factors (e.g. force, time, depth and distance) were statistically analysed. The
      samples were processed for histology and immunohistochemistry. After 1-3 weeks of
      culture in the in-house-designed in vitro bioreactor, fluorescence imaging
      confirmed that additional mechanical loading increased the viable cell numbers
      over time as compared with the control. Cells of various phenotypes formed
      different patterns away from the reaction tube. The cells in the middle part of
      the gel showed enhanced alkaline phosphatase staining at week 1 but reduced
      staining at weeks 2 and 3. Additional loading enhanced Sirius Red and type I
      collagen staining compared with the control. We have thus successfully developed
      a novel in-house-designed in vitro bioreactor mimicking the biting force to
      enhance hDPSC osteogenesis in an agarose scaffold and to promote bone formation
      and/or prevent bone resorption.

PMID- 24916614
TI  - Virus-induced gene silencing in transgenic plants: transgene silencing and
      reactivation associate with two patterns of transgene body methylation.
AB  - We used bisulfite sequencing to study the methylation of a viral transgene whose
      expression was silenced upon plum pox virus infection of the transgenic plant and
      its subsequent recovery as a consequence of so-called virus-induced gene
      silencing (VIGS). VIGS was associated with a general increase in the accumulation
      of small RNAs corresponding to the coding region of the viral transgene. After
      VIGS, the transgene promoter was not methylated and the coding region showed
      uneven methylation, with the 5' end being mostly unmethylated in the recovered
      tissue or mainly methylated at CG sites in regenerated silenced plants. The
      methylation increased towards the 3' end, which showed dense methylation in all
      three contexts (CG, CHG and CHH). This methylation pattern and the corresponding
      silenced status were maintained after plant regeneration from recovered silenced
      tissue and did not spread into the promoter region, but were not inherited in the
      sexual offspring. Instead, a new pattern of methylation was observed in the
      progeny plants consisting of disappearance of the CHH methylation, similar CHG
      methylation at the 3' end, and an overall increase in CG methylation in the 5'
      end. The latter epigenetic state was inherited over several generations and did
      not correlate with transgene silencing and hence virus resistance. These results
      suggest that the widespread CG methylation pattern found in body gene bodies
      located in euchromatic regions of plant genomes may reflect an older silencing
      event, and most likely these genes are no longer silenced.

PMID- 24916615
TI  - Structured pharmaceutical analysis of the Systematic Tool to Reduce Inappropriate
      Prescribing is an effective method for final-year medical students to improve
      polypharmacy skills: a randomized controlled trial.
AB  - Medical students may not be adequately trained to prescribe appropriately to
      older adults with polypharmacy. This study addressed how to teach students to
      minimize inappropriate polypharmacy. Final-year medical students (N = 106) from
      two Dutch schools of medicine participated in this randomized controlled trial
      with a pre/posttest design. The Systematic Tool to Reduce Inappropriate
      Prescribing (STRIP) was used as the intervention. This medication review tool
      consists of five steps and is part of the Dutch multidisciplinary guideline on
      polypharmacy. Step two is a structured pharmaceutical analysis of drug use,
      assessed using six questions regarding undertreatment, ineffective treatment,
      overtreatment, potential adverse effects, contraindications or interactions, and
      dose adjustments. It is used in combination with the Screening Tool to Alert
      doctors to Right Treatment and the Screening Tool of Older Person's Prescriptions
      checklists. Students were asked to optimize the medication lists of real people,
      making use, or not, of the STRIP. The number of correct or potentially harmful
      decisions that the students made when revising the lists was determined by
      comparison with expert consensus. Students who used the STRIP had better scores
      than control students; they made more correct decisions (9.3 vs 7.0, 34%; P <
      .001, correlation coefficient (r) = 0.365) and fewer potentially harmful
      decisions (3.9 vs 5.6, -30%; P < .001, r = 0.386). E-learning did not have a
      different effect from that of non-E-learning methods. Students were satisfied
      with the method. The STRIP method is effective in helping final-year medical
      students improve their prescribing skills.

PMID- 24916617
TI  - Editorial.

PMID- 24916616
TI  - Digital pathology services in acute surgical situations.

PMID- 24916618
TI  - Diagnostic criteria and the standardized diagnostic interview for posttraumatic
      embitterment disorder (PTED).
AB  - Objective. The posttraumatic embitterment disorder (PTED) is a specific form of
      adjustment disorder. The purpose of this study was to specify diagnostic criteria
      of PTED, and to develop a standardized instrument which allows a standardized
      diagnosis. Method. Data were obtained from 50 clinically defined PTED patients
      and 50 patients with other mental disorders (N=100) using a semi-standardized
      interview for PTED. Based on the answers of the participants, the description of
      PTED was refined and a standardized diagnostic interview for PTED was derived.
      Results. The diagnostic algorithm reached satisfying levels of sensitivity (94%)
      and specificity (92%). Conclusion. The diagnostic interview for PTED allows a
      standardized diagnosis of PTED. 

PMID- 24916619
TI  - Experience of quality of life and attitude to care and treatment in patients with
      schizophrenia: Role of cross-sectional remission.
AB  - Objective. The concept of cross-sectional remission was investigated in a sample
      of patients with schizophrenia. A total of 243 patients were tested for quality
      of life, burden and handicap, insight and satisfaction with the care provided in
      an epidemiological study. The question addressed was if remission is of
      importance for outcome. Methods. Cross-sectional remission was defined by
      applying the symptom criteria of remission, where none of eight selected PANSS
      items should exceed 3 points. Out of 243 patients, 38% were in met cross
      sectional remission. Quality of life was assessed with the MOS SF-36 and the
      Rosser Index. The patients' understanding of their illness was assessed based on
      symptoms and disorder insight. Finally, attitudes to care and health service were
      assessed by the UKU/Consumer Satisfaction Questionnaire and the Drug Attitude
      Inventory. Results. Patients who were in cross-sectional remission reported
      higher quality of life and reduced burden related to the disorder, a greater
      level of insight into their symptoms and the illness, and a more positive
      attitude to treatment, including drugs. Conclusion. This study implies that
      remission, here expressed in terms of cross-sectional remission, is of importance
      for patients' well-being. Patients who had no interference from symptoms in their
      daily functioning found their life better, had a superior insight and were more
      positive to treatment. 

PMID- 24916620
TI  - Health-related quality of life in patients with conversion disorder with
      seizures.
AB  - Objective. The concept of Health-Related Quality of Life (HRQOL) is important for
      both the prevention and progress of psychiatric diseases. In the literature, we
      are aware that there are a few studies on HRQOL among patients with conversion
      disorder with seizure. Our aim is to measure the HRQOL in Turkey among patients
      with conversion disorder with seizure and to compare the quality of life of this
      study group to a healthy control group and to different types of epileptic
      patient groups. Methods. A total of 330 subjects was included in this study; 102
      patients were included in the conversion disorder group, 121 patients were
      included in the epileptic group and 93 subjects were included in the healthy
      control group. WHOQOL-100 scale and Trait Anxiety Inventory (TAI) were
      administered to these groups. Results. HRQOL for the patients with conversion
      disorder was worse than the control group except for the environment and social
      relations domains. The generalized epilepsy patients had better physical and
      psychological health, compared with the patients with conversion disorder.
      Compared with the partial epilepsy group, HRQOL for the patients with conversion
      disorder was better in psychological, environmental, social relationship domains.
      Conclusion. Considering these disorders, patients with conversion disorder need
      long-term psychiatric treatment. Carrying out this study in our country will be
      an advantage for the cross-cultural studies which will be undertaken out in the
      future. 

PMID- 24916621
TI  - Attention and executive function in people with schizophrenia: Relationship with
      social skills and quality of life.
AB  - Objective. Executive function and attention are highly complex cognitive
      constructs that typically reveal evidence of impairment in people with
      schizophrenia. Studies in this area have traditionally utilised abstract tests of
      cognitive function and the importance of using more ecologically valid tests has
      not been extensively recognised. In addition, there has been little previous
      examination of the relationship between these key cognitive abilities and social
      functioning and quality of life in this population. Methods. Thirty-six
      schizophrenic patients and 15 controls were assessed on the Behavioural
      Assessment of the Dysexecutive Syndrome (BADS) test, three subtests from the Test
      of Everyday Attention (TEA), a measure of social functioning and a quality of
      life measure. Results. Analysis of subtest scores revealed that patients were
      impaired on all attentional measures, but only one BADS subtest score in addition
      to the BADS profile score. However, 23 patients demonstrated no impairment in
      their BADS profile scores whilst being impaired on at least one attentional
      measure. Only the BADS profile score predicted social functioning and quality of
      life. Conclusions. Ecologically valid tests of attention and executive function
      can play an important role in defining the cognitive deficits in schizophrenia
      and how such deficits relate to social function and quality of life. 

PMID- 24916622
TI  - Psychosocial predictors of psychiatric disorders after living donor liver
      transplantation.
AB  - Objective. Adult recipients of living donor liver transplantation (LDLT) often
      have psychiatric disorders before and after surgery. The aim of this study was to
      investigate pretransplant psychosocial factors that can be used to predict
      psychiatric disorders after LDLT. Methods. The subjects were 67 recipients of
      adult-to-adult LDLT at Kyoto University Hospital, Japan, from November 2001
      through July 2003. All subjects were interviewed and examined by means of the
      Beck Depression Inventory, State-Trait Anxiety Inventory, World Health
      Organization Quality-of-Life Assessment-26, and Psychosocial Assessment of
      Candidates for Transplantation (PACT) just before LDLT. The subjects were
      followed up for 90 days for the presence of psychiatric disorders. Results. Mood
      disorders in the past, inability to maintain a healthy lifestyle, family support
      instability, and suicidal ideation just before LDLT might be predictors of major
      depressive disorder after LDLT. Delirium just before LDLT might be a predictor of
      delirium after LDLT, while no psychosocial factors associated with posttransplant
      delirium could be found. Conclusion. Information about life history rather than
      any psychological examination is important for predicting the occurrence of
      posttransplant depression. PACT is useful for obtaining information about the
      life history of LDLT recipients. 

PMID- 24916623
TI  - Clinical characteristics of agitated psychotic patients treated with an oral
      antipsychotics attended in the emergency room setting: NATURA study.
AB  - Purpose. Prospective observational study to describe the clinical characteristics
      of patients with acute psychosis and agitation who receive oral
      psychopharmacological treatment at psychiatric emergency services (PES). Methods.
      A total of 278 patients with acute psychosis and agitation were admitted to PES
      and received oral psychopharmacological treatment. Diagnosis at admission,
      agitation level at entry and discharge, use of mechanical restraints,
      pharmacological and time to reintervention were prospectively explored. Severity
      of the disease was evaluated according to the Positive and Negative Syndrome
      Scale-Excitement Component (PANSS-EC), Agitation Calmness Evaluation Scale (ACES)
      and Clinical Global Impression-Severity (CGI-S) at admission, before first
      reintervention (if any) and at discharge from PES. Results. Most prevalent
      diagnoses were schizophrenia (77%) and bipolar disorder (12.2%). Mean (SD) scores
      in rating scales at baseline and at discharge were, respectively: PANSS-EC,
      20.38(5.3) and 13.04 (5.5); CGI-S, 3.86(1.1) and 2.17(0.9); and ACES, 2.35(0.6)
      and 3.60(1.1). A total of 21.6% (60/278) of the patients required mechanical
      restraints and 38.1% (106/278) reintervention. From the emergency room, 20.5%
      patients went home while 71.2% were transferred to inpatient units. Conclusion.
      Clinical characteristics of psychotic agitated patients may help in deciding
      which type of treatment should be used and may be useful for the design of future
      prospective trials to explore treatment of agitation. 

PMID- 24916624
TI  - The impact of obsessive-compulsive disorder in pregnancy on quality of life.
AB  - Aim. To examine the effects of obsessive-compulsive disorder (OCD) on quality of
      life in pregnant women. Material and method. Twenty-five pregnant women diagnosed
      as OCD in two university outpatient clinics were included for the study. Twenty
      five pregnant women with no mental disorders and the same sociodemographic
      properties were taken as the control group. The diagnosis of OCD was confirmed
      with the DSM-IV Axis-I Disorders Structured Clinic Interview Diagnosis/Clinic
      Version (SCID-I/CV). In order to measure the severity of OCD Yale-Brown Obsession
      and Compulsion Scale was performed. Quality of life was evaluated by WHO (World
      Health Organisation) Life Quality Scale - Short Form (WHOQOL-Brief). Results. The
      whole subgroup of points of WHOQOL-Brief was significantly lower in OCD patients
      compared to control group (in all subgroups P<0.01). There was a negative
      correlation between the Y-BOCS obsession and compulsion subpoints and total
      points with the physical health (P <0.05), psychological health (P <0.001) and
      social relationship (P <0.01) of WHOQOL-Brief. No significant association was
      found with enviromental areas. Besides, there was a negative correlation between
      the duration of OCD and WHOQOL-Brief psychological health subarea (P <0.05).
      Conclusion. OCD negatively effects the quality of life in pregnant women and is
      correlated with the severity of the disorder. 

PMID- 24916625
TI  - Frontotemporal lobar degeneration with motor neurone disease (FTLD/MND):
      Presentations in psychiatric practice.
AB  - Background. Concurrence of frontotemporal lobar degeneration with clinical
      features of motor neurone disease (FTLD/MND) is a recognised cause of dementia
      with widely accepted diagnostic criteria, but it is not mentioned in DSM-IV-TR.
      Aim. To draw attention to cases of FTLD/MND referred by psychiatrists, or already
      under the care of psychiatrists at time of referral, to a dedicated Cognitive
      Function Clinic. Methods. Prospective study of FTLD/MND cases, 1999-2007
      inclusive; case note review. Results. Nine of 13 cases of FTLD/MND were either
      referred by or already under the care of a psychiatrist. Although most had been
      identified as having a dementia, in none had the correct diagnosis been made. All
      patients had signs of motor neurone pathology on clinical examination, sometimes
      subtle, in addition to cognitive and psychiatric features. A wide variety of
      drugs had been prescribed including antidepressants, antipsychotics,
      cholinesterase inhibitors, and memantine. Conclusions. A high index of clinical
      suspicion is required to identify cases of possible FTLD/MND, and thereby
      initiate appropriate investigations and management and avoid inappropriate
      medication. Absence of FTLD/MND in DSM-IV-TR may further handicap psychiatrists
      in making this diagnosis. 

PMID- 24916626
TI  - The bipolar diathesis of treatment-resistant major depressive disorder.
AB  - Objective. In this study, we determined the prevalence of bipolarity in patients
      with treatment-resistant depression (TRD) by investigating demographic and
      clinical characteristics, diagnostic subtypes and illness outcome of patients
      with resistant depression. Methods. A medical record review of patients who were
      admitted to a university hospital with the diagnosis of major depressive disorder
      (MDD) was conducted. DSM-IV diagnoses at the index hospitalization and 6 months
      after discharge and detailed clinical information were obtained. We categorized
      subjects into a TRD group or a non-TRD group and re-evaluated the patients using
      the criteria for bipolar spectrum disorders. Results. There were 281 patients
      diagnosed with MDD. At discharge, the number of patients who fulfilled the
      criteria for BSD was higher in the TRD group (47.1%) than in the non-TRD group
      (3.8%) (P<0.001). At the end of the 6-month follow-up period, the diagnoses of 38
      patients were changed; 18 (26.5%) of the TRD group were subsequently classified
      as having a bipolar disorder, as were seven (3.3%) in the non-TRD group
      (P<0.001). There was no difference between these two groups for other clinical
      and demographic variables. Conclusion. The findings of this study suggest that
      many patients with TRD have a bipolar diathesis. 

PMID- 24916627
TI  - Elevated serum creatine kinase levels in psychiatric practice: differential
      diagnosis and clinical significance: A brief, practical guideline for clinicians.
AB  - Introduction. Elevated serum CK levels often occur in psychiatric in-patient
      practice. Although the majority of cases are benign and temporary, it is
      important to recognize and treat these conditions. Aims. To discuss the etiology,
      the clinical significance and the management of elevated creatine kinase levels
      in psychiatric in-patient practice, focusing on antipsychotic-induced
      rhabdomyolysis. To compare the pathogenesis and the clinical features of
      rhabdomyolysis and neuroleptic malignant syndrome. Methods. Review of the
      literature. Results. A brief, practical guideline is introduced, which may help
      clinicians in the differential diagnosis and in the management of patients with
      elevated creatine kinase activity in emergent psychiatric practice. Conclusions.
      The most common etiologic factors (prescription drugs, alcohol, physical reasons,
      cardiac etiology) and clinical syndromes (rhabdomyolysis, neuroleptic malignant
      syndrome, acute coronary syndrome) should be considered, when elevated creatine
      kinase levels are encountered in psychiatric in-patients. Routine creatine kinase
      measurements in asymptomatic patients on antipsychotic medications are not
      recommended, but patients should be carefully followed for the development of
      rhabdomyolysis, when muscular symptoms arise. Careful monitoring of symptoms and
      potential complications is critical in order to avoid devastating clinical
      consequences. Cautiously challenging patients with another antipsychotic after an
      antipsychotic-induced rhabdomyolysis is recommended to decrease the possibility
      of recurrence. 

PMID- 24916628
TI  - Gender effect on clinical features and drug treatment response in social anxiety
      disorder (social phobia).
AB  - Objective. To investigate differences concerning clinical and treatment response
      features in male and female patients with social anxiety disorder (SOAD). Method.
      Male (n=41) and female patients (n=21) with SOAD were compared with regard to age
      and mode of onset; SOAD subtype; symptom severity; presence of comorbid
      psychiatric conditions; and response after drug treatment. The chi(2)-test was
      used for comparisons between categorical variables and Student's t-test for
      continuous variables. The adopted level of statistic significance was 5%.
      Results. Male patients had a higher mean age (t= -2.9; df =42; P=0.006), more
      severe initial symptoms (t =-2.6; df =37.4; P =0.01) and, more often, more than
      one comorbid psychiatric condition (chi(2)=10.98; df =1; P =0.001). Alcohol abuse
      was more frequent in men (chi(2)=7.62; df =1; P =0.006). With regard to treatment
      response, male patients displayed greater reductions in the severity of their
      baseline symptoms. Patients with SOAD were randomly selected from both samples in
      order to generate subgroups of 18 male and 18 female age-matched patients.
      Despite controlling for age, we still found that men exhibited a trend toward
      greater severity of symptoms at baseline than women with SOAD (t =-1.8; df =33.1;
      P =0.07). Conclusion. The findings suggest differences concerning initial
      severity and comorbidity rates between men and women suffering from SOAD. 

PMID- 24916629
TI  - Prescribing of the antidepressant duloxetine: Can local clinical audit findings
      facilitate medicines management decisions?
AB  - Introduction. Discussions regarding the inclusion of a new antidepressant within
      local formulary lists and prescribing guidelines may be facilitated by audits of
      local prescribing practice, conducted some months after the drug first becomes
      available for clinical use. Method. Development of five audit standards and
      retrospective case-note review of prescribing recommendations for the serotonin
      noradrenaline reuptake inhibitor duloxetine, made in five local outpatient
      clinics. Results. Follow-up data were available for audit in 27 of 43 sets of
      medical notes. In the majority of patients (84%), the primary diagnosis was
      recurrent unipolar depressive disorder, the current episode having proven
      resistant to treatment with two other antidepressants. Where comments were made,
      notes indicated that 81% of patients that received duloxetine had improved and
      94% had tolerated it without reported problems. Conclusions. In this sample,
      duloxetine prescribing in the first months after it became available appeared to
      occur within an appropriate patient group. Prospective evaluations in other
      clinical samples are warranted. 

PMID- 24916630
TI  - Long-term results of pneumatic dilatation for relapsing symptoms of achalasia
      after Heller myotomy.
AB  - BACKGROUND: The aim of this study was to assess the efficacy and safety of
      pneumatic dilatation (PD) to treat symptom recurrence after Heller myotomy (HM).
      METHODS: Consecutive patients receiving PD for relapsing symptoms following prior
      HM were included in this retrospective single-center study. Eckardt score <=3
      and/or ? Eckardt (difference between Eckardt score before and after dilatation)
      >=3 defined the success of initial dilatation. Patients who maintained response
      longer than 2 months after initial dilatation were defined as short-term
      responders. Relapsers were offered further on-demand dilatation. Remission was
      defined as an Eckardt score <=3 at the study endpoint. Kaplan-Meier survival
      curves were used to determine relapse rates. KEY RESULTS: Eighteen patients (11
      women, seven men) were included from January 2004 to January 2013. Ten patients
      had type I achalasia, and seven had type III, according to the Chicago
      classification. Thirty-nine PDs were performed (1.5 [1-2.25] per patient). All
      patients had short-term responses. The remission rate at the endpoint, after a
      median follow-up of 33 months, was 78%, but 44% were treated with on-demand PD
      during the follow-up interval. The proportions of patients without relapse and
      subsequent PD were 72% at 12 months, 65% at 24 and 36 months, and 49% at 48
      months. No factors predictive of long-term response, particularly the type of
      achalasia, could be identified in this series. There were no perforations.
      CONCLUSIONS & INFERENCES: In treating symptom recurrence following HM, PD was
      safe and effective over the long term when combined with subsequent PD.

PMID- 24916631
TI  - Knowledge and perceptions about the health impact of climate change among health
      sciences students in Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Climate change affects human health in various ways. Health planners
      and policy makers are increasingly addressing potential health impacts of climate
      change. Ethiopia is vulnerable to these impacts. Assessing students' knowledge,
      understanding and perception about the health impact of climate change may
      promote educational endeavors to increase awareness of health impacts linked to
      climate change and to facilitate interventions. METHODS: A cross-sectional study
      using a questionnaire was carried out among the health science students at
      Haramaya University. Quantitative methods were used to analyze the results.
      RESULT: Over three quarters of the students were aware of health consequences of
      climate change, with slightly higher rates in females than males and a range from
      60.7% (pharmacy students) to 100% (environmental health and post-graduate public
      health students). Electronic mass media was reportedly the major source of
      information but almost all (87.7%) students stated that their knowledge was
      insufficient to fully understand the public health impacts of climate change.
      Students who knew about climate change were more likely to perceive it as a
      serious health threat than those who were unaware of these impacts [OR: 17.8, 95%
      CI: 8.8-32.1] and also considered their departments to be concerned about climate
      change (OR: 7.3, 95% CI: 2.8-18.8), a perception that was also significantly more
      common among students who obtained their information from the electronic mass
      media and schools (p < 0.05). Using electronic mass media was also significantly
      associated with knowledge about the health impacts of climate change. CONCLUSION:
      Health sciences students at Haramaya University may benefit from a more
      comprehensive curriculum on climate change and its impacts on health.

PMID- 24916632
TI  - Computationally efficient and accurate enantioselectivity modeling by clusters of
      molecular dynamics simulations.
AB  - Computational approaches could decrease the need for the laborious high
      throughput experimental screening that is often required to improve enzymes by
      mutagenesis. Here, we report that using multiple short molecular dynamics (MD)
      simulations makes it possible to accurately model enantioselectivity for large
      numbers of enzyme-substrate combinations at low computational costs. We chose
      four different haloalkane dehalogenases as model systems because of the
      availability of a large set of experimental data on the enantioselective
      conversion of 45 different substrates. To model the enantioselectivity, we
      quantified the frequency of occurrence of catalytically productive conformations
      (near attack conformations) for pairs of enantiomers during MD simulations. We
      found that the angle of nucleophilic attack that leads to carbon-halogen bond
      cleavage was a critical variable that limited the occurrence of productive
      conformations; enantiomers for which this angle reached values close to 180
      degrees  were preferentially converted. A cluster of 20-40 very short (10 ps) MD
      simulations allowed adequate conformational sampling and resulted in much better
      agreement to experimental enantioselectivities than single long MD simulations
      (22 ns), while the computational costs were 50-100 fold lower. With single long
      MD simulations, the dynamics of enzyme-substrate complexes remained confined to a
      conformational subspace that rarely changed significantly, whereas with multiple
      short MD simulations a larger diversity of conformations of enzyme-substrate
      complexes was observed. 

PMID- 24916633
TI  - Nonunion after trapeziometacarpal arthrodesis: comparison between K-wire and
      internal fixation.
AB  - We reviewed 63 trapeziometacarpal arthrodeses (57 patients) performed in our unit
      between April 2007 and May 2013 for osteoarthritis. K-wires, plates, headless
      compression screws and memory staples were used for fixation. The average age of
      patients was 50 (range 20-78) years and there were 36 men and 21 women with a
      mean follow-up of 36 (range 6-62) months. K-wires were used in 31 cases, staples
      in 12, plates in five, and screws in 15 joints. The overall non-union rate was
      11%, however, when using K-wires for fixation, it was 20%. Union was achieved in
      all cases when staples or screws were used for fixation. Disabilities of the Arm,
      Shoulder and Hand scores were higher in cases where non-union occurred compared
      with those that united (66.7 vs. 21.9). Trapeziometacarpal arthrodesis for
      osteoarthritis gives good clinical outcome with lower (DASH) scores when union
      occurs. K-wire fixation led to a 20% non-union rate, and as a result, the senior
      author no longer uses this method of fixation. 

PMID- 24916634
TI  - The influence of education and income on responses to the QuickDASH
      questionnaire.
AB  - We studied the influence of levels of income and education on QuickDASH scores.
      The scores were collected in a random sample of 1376 residents of Norway. The
      level of income was divided into four bands and level of education into five
      bands. The mean QuickDASH score for both men and women fell with every increase
      in education and income level. For women the mean score was 30 for those with the
      shortest education and 9 for those with the longest (p < 0.001). The
      corresponding figures for men were 19 and 7 (p < 0.01). The women with the lowest
      level of income had a mean score of 23, compared with 8 for women with the
      highest income level (p < 0.001). For men the corresponding mean scores were 20
      and 5 (p < 0.001). Analysis of variance showed that age alone accounted for 16%
      of the variability of the scores among women and 7% among men. When levels of
      education and income were added to the analysis, these three factors accounted
      for 21% of the variability among women and 13% among men. We conclude that
      socioeconomic factors significantly influence QuickDASH scores. LEVEL OF
      EVIDENCE: 3.

PMID- 24916635
TI  - Caudal vertebral body articular surface morphology correlates with functional
      tail use in anthropoid primates.
AB  - Prehensile tails, capable of suspending the entire body weight of an animal, have
      evolved in parallel in New World monkeys (Platyrrhini): once in the Atelinae
      (Alouatta, Ateles, Brachyteles, Lagothrix), and once in the Cebinae (Cebus,
      Sapajus). Structurally, the prehensile tails of atelines and cebines share
      morphological features that distinguish them from nonprehensile tails, including
      longer proximal tail regions, well-developed hemal processes, robust caudal
      vertebrae resistant to higher torsional and bending stresses, and caudal
      musculature capable of producing higher contractile forces. The functional
      significance of shape variation in the articular surfaces of caudal vertebral
      bodies, however, is relatively less well understood. Given that tail use differs
      considerably among prehensile and nonprehensile anthropoids, it is reasonable to
      predict that caudal vertebral body articular surface area and shape will respond
      to use-specific patterns of mechanical loading. We examine the potential for
      intervertebral articular surface contour curvature and relative surface area to
      discriminate between prehensile-tailed and nonprehensile-tailed platyrrhines and
      cercopithecoids. The proximal and distal intervertebral articular surfaces of the
      first (Ca1), transitional and longest caudal vertebrae were examined for
      individuals representing 10 anthropoid taxa with differential patterns of tail
      use. Study results reveal significant morphological differences consistent with
      the functional demands of unique patterns of tail use for all vertebral elements
      sampled. Prehensile-tailed platyrrhines that more frequently use their tails in
      suspension (atelines) had significantly larger and more convex intervertebral
      articular surfaces than all nonprehensile-tailed anthropoids examined here,
      although the intervertebral articular surface contour curvatures of large,
      terrestrial cercopithecoids (i.e., Papio sp.) converge on the ateline condition.
      Prehensile-tailed platyrrhines that more often use their tails in tripodal
      bracing postures (cebines) are morphologically intermediate between atelines and
      nonprehensile tailed anthropoids.

PMID- 24916636
TI  - CQC says it failed to respond adequately to concerns about care home deaths.

PMID- 24916638
TI  - Good Friday slaughter.

PMID- 24916637
TI  - Unusual interaction of RNA polymerase with the bacteriophage Mu middle promoter
      Pm in the absence of its activator protein Mor.
AB  - The bacteriophage Mu Mor activator protein is absolutely required for
      transcription from the Mu middle promoter P(m). However, when RNA polymerase
      (RNAP) was incubated with P(m) DNA in the absence of Mor, a band at promoter
      position -51 was hypersensitive to DNase I cleavage, demonstrating an interaction
      of RNAP with the promoter DNA. The hypersensitivity was similar at four different
      lengths of P(m) DNA assayed from -62 to +10, -62 to +46, -96 to +10, and -96 to
      +46. The hypersensitivity occurred equally well at 5  degrees C, 15  degrees C,
      and 30  degrees C, indicating that it did not require open complex formation,
      which only occurred at 30  degrees C. The -51 hypersensitivity at 5  degrees C
      and 15  degrees C was eliminated by the addition of heparin, consistent with the
      possibility that it arose by formation of unstable closed complexes of RNAP bound
      to P(m) DNA. Generation of the hypersensitive band required the complete RNAP
      with its alphaCTDs, but neither the alphaCTD nor intact alpha were sufficient for
      the interaction and resulting hypersensitivity. There was no correlation between
      the level of hypersensitivity observed in vitro and the level of Pm activity in
      vivo, as assayed by the Mor-dependent production of beta-galactosidase from a
      P(m)-lacZ fusion. In an "order of addition" experiment, preincubation of P(m) DNA
      with Mor followed by addition of RNAP led to the fastest open complex formation,
      whereas preincubation of P(m) DNA with RNAP gave the slowest. These results
      support the conclusion that Mor recruits RNAP to P(m) rather than reposition a
      prebound RNAP, as occurs for C-dependent repositioning of RNAP at the Mu late
      promoter Pmom .

PMID- 24916639
TI  - Interleukin-17 receptor expression on vascular endothelial cells of masses of
      skeletal extramedullary disease in myeloma patients.
AB  - The goal of the study was to investigate the expression of interleukin-17 (IL-17)
      and IL-17 receptor (IL-17R) in patients with myeloma bone diseases (MBD) and
      skeletal extramedullary disease (skeletal EMD). The levels of IL-17 were
      determined using ELISA. The expression of IL-17R on vascular endothelial cells of
      bone marrow (BM) and masses of skeletal EMD was detected using
      immunohistochemistry. The results showed an elevated IL-17 level in BM of BMD and
      skeletal EMD patients. The microvessel density (MVD) was significantly increased
      in the masses of skeletal EMD. IL-17R was almost exclusively expressed by
      endothelial cells, not by myeloma cells in the masses of skeletal EMD patients.
      We concluded that EMD masses showed increased angiogenesis mediated by IL-17
      pathway and in part this may help in myeloma cell-growth under these conditions.

PMID- 24916640
TI  - Extra fluids for breastfeeding mothers for increasing milk production.
AB  - BACKGROUND: Breastfeeding is known to be the biological norm. Despite this, many
      women wean their babies because of perceived insufficient breast milk production.
      Mothers are sometimes advised to increase their fluid intake in the hope that
      this could improve breast milk production. The effect of extra fluid on human
      breast milk production is not well established, however. OBJECTIVES: To assess
      the effect of extra fluid for breastfeeding mothers on milk production/supply and
      infant growth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (27 April 2014), MEDLINE (1966 to 27 April 2014), African
      Journals Online (27 April 2014) and reference lists of retrieved studies.
      SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled
      trials on extra fluids for breastfeeding mothers. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed the potential studies for inclusion and
      assessed trial quality. MAIN RESULTS: Five trial reports were retrieved using the
      search strategies. Four trials were excluded. We did not identify any randomised
      controlled trials for inclusion but we included one quasi-randomised study
      (involving 210 women) that evaluated the effect of extra fluid for breastfeeding
      mothers on breastfeeding outcomes. The study was considered to be at a high risk
      of bias. Only one of this review's primary outcomes was reported (breast milk
      production (as defined by the trialist)) but data were not in a suitable format
      for analysis (no standard deviations or standard errors were reported). The
      trialist reported that advising women to drink extra fluids did not improve
      breast milk production. No data were reported for the review's other primary
      outcomes: satisfactory weight gain in the infant (as defined by the trialists)
      and duration of exclusive breastfeeding (months). Similarly, no data were
      reported for any of this review's secondary outcomes: duration of any
      breastfeeding; mother's satisfaction with breastfeeding; hydration in mother;
      dehydration in the infant; or episodes of gastrointestinal illness. AUTHORS'
      CONCLUSIONS: This review only identified one small quasi-randomised controlled
      trial of low quality and high risk of bias. The study provided limited data on
      only one of this review's primary outcomes, breast milk production, but the data
      were not reported in a format that permitted further analysis. The trialist
      reported that extra fluids did not improve breast milk production. However, this
      outcome was measured by using test feeds (also known as test weighing). In the
      1950s, when the study was conducted, it was common for babies in developed
      countries to be weighed before and after a feed, known as test weighing or test
      feeding. However, this practice is not now routinely practiced for term infants
      due to concerns about lack of precision as a measure of breast milk production.
      The included study did not report on this review's other primary outcomes
      (satisfactory weight gain in the infant or duration of exclusive breastfeeding)
      nor any of the review's secondary outcomes.The effect of additional fluids for
      breastfeeding mothers remains unknown, due to a lack of well-conducted trials.
      However, because the physiological basis for any such improvement remains
      unclear, the conduct of further clinical trials may not be a priority. There is
      not enough evidence to support an increased fluid intake beyond what
      breastfeeding mothers are likely to require to meet their physiological needs.

PMID- 24916641
TI  - Missense variant in CCDC22 causes X-linked recessive intellectual disability with
      features of Ritscher-Schinzel/3C syndrome.
AB  - Ritscher-Schinzel syndrome (RSS)/3C (cranio-cerebro-cardiac) syndrome
      (OMIM#220210) is a rare and clinically heterogeneous developmental disorder
      characterized by intellectual disability, cerebellar brain malformations,
      congenital heart defects, and craniofacial abnormalities. A recent study of a
      Canadian cohort identified homozygous sequence variants in the KIAA0196 gene,
      which encodes the WASH complex subunit strumpellin, as a cause for a form of
      RSS/3C syndrome. We have searched for genetic causes of a phenotype similar to
      RSS/3C syndrome in an Austrian family with two affected sons. To search for
      disease-causing variants, whole-exome sequencing (WES) was performed on samples
      from two affected male children and their parents. Before WES, CGH array
      comparative genomic hybridization was applied. Validation of WES and segregation
      studies was done using routine Sanger sequencing. Exome sequencing detected a
      missense variant (c.1670A>G; p.(Tyr557Cys)) in exon 15 of the CCDC22 gene, which
      maps to chromosome Xp11.23. Western blots of immortalized lymphoblastoid cell
      lines (LCLs) from the affected individual showed decreased expression of CCDC22
      and an increased expression of WASH1 but a normal expression of strumpellin and
      FAM21 in the patients cells. We identified a variant in CCDC22 gene as the cause
      of an X-linked phenotype similar to RSS/3C syndrome in the family described here.
      A hypomorphic variant in CCDC22 was previously reported in association with a
      familial case of syndromic X-linked intellectual disability, which shows
      phenotypic overlap with RSS/3C syndrome. Thus, different inactivating variants
      affecting CCDC22 are associated with a phenotype similar to RSS/3C syndrome. 

PMID- 24916642
TI  - Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi
      Syndrome.
AB  - The SNORD116 locus lies in the 15q11-13 region of paternally expressed genes
      implicated in Prader-Willi Syndrome (PWS), a complex disease accompanied by
      obesity and severe neurobehavioural disturbances. Cases of PWS patients with a
      deletion encompassing the SNORD116 gene cluster, but preserving the expression of
      flanking genes, have been described. We report a 23-year-old woman who presented
      clinical criteria of PWS, including the behavioural and nutritional features,
      obesity, developmental delay and endocrine dysfunctions with hyperghrelinemia. We
      found a paternally transmitted highly restricted deletion of the SNORD116 gene
      cluster, the shortest described to date (118 kb). This deletion was also present
      in the father. This finding in a human case strongly supports the current
      hypothesis that lack of the paternal SNORD116 gene cluster has a determinant role
      in the pathogenesis of PWS. Moreover, targeted analysis of the SNORD116 gene
      cluster, complementary to SNRPN methylation analysis, should be carried out in
      subjects with a phenotype suggestive of PWS. 

PMID- 24916643
TI  - Impact on parents of HLA-DQ2/DQ8 genotyping in healthy children from coeliac
      families.
AB  - Due to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA
      typing can be used for risk determination of the disease. This study was designed
      to evaluate the knowledge of parents from coeliac families regarding HLA-typing
      and the impact of HLA-typing on the perception of the health of their children. A
      structured questionnaire was sent to the Dutch, Spanish and German parents
      participating with their child in the European PreventCD study on disease
      prevention in high-risk families, addressing parents' understanding of and
      attitude towards HLA-typing, distress related to HLA-typing and perceived health
      and health-related quality of life of their children. Sixty-eight percent of
      parents of 515 children returned the questionnaires, with 85% of children being
      DQ2/DQ8 positive. The majority of all parents answered the questions on knowledge
      correctly. Forty-eight percent of parents of DQ2/DQ8-negative children thought
      their child could develop coeliac disease. More distress was reported by parents
      of DQ2/DQ8-positive children (P<0.001). All parents showed few regrets and would
      repeat HLA-typing in future children. Perceived health and health-related quality
      of life were similar. In conclusion, we can say that misinterpretation of DQ2/DQ8
      negative results by parents is frequent. DQ2/DQ8-positive results do not affect
      perceived health and health-related quality of life of children but may cause
      temporary negative feelings among parents. Parents of coeliac families seem to
      support HLA-typing. 

PMID- 24916644
TI  - The role of the genetic counsellor: a systematic review of research evidence.
AB  - In Europe, genetic counsellors are employed in specialist genetic centres or
      other specialist units. According to the European Board of Medical Genetics, the
      genetic counsellor must fulfil a range of roles, including provision of
      information and facilitation of psychosocial adjustment of the client to their
      genetic status and situation. To evaluate the extent to which genetic counsellors
      fulfil their prescribed roles, we conducted a systematic review of the published
      relevant scientific evidence. We searched five relevant electronic databases
      (Medline, CINAHL, SocIndex, AMED and PsychInfo) using relevant search terms and
      handsearched four subject-specific journals for research-based papers published
      in English between 1 January 2000 and 30 June 2013. Of 419 potential papers
      identified initially, seven satisfied the inclusion criteria for the review.
      Themes derived from the thematic analysis of the data were: (i) rationale for
      genetic counsellors to provide care, (ii) appropriate roles and responsibilities
      and (iii) the types of conditions included in the genetic counsellor caseload.
      The findings of this systematic review indicate that where genetic counsellors
      are utilised in specialist genetic settings, they undertake a significant
      workload associated with direct patient care and this appears to be acceptable to
      patients. With the burden on genetic services, there is an argument for the
      increased use of genetic counsellors in countries where they are under-utilised.
      In addition, roles undertaken by genetic counsellors in specialist genetic
      settings could be adapted to integrate genetic counsellors into multi
      disciplinary teams in other specialisms. 

PMID- 24916646
TI  - Sandwich corrected standard errors in family-based genome-wide association
      studies.
AB  - Given the availability of genotype and phenotype data collected in family
      members, the question arises which estimator ensures the most optimal use of such
      data in genome-wide scans. Using simulations, we compared the Unweighted Least
      Squares (ULS) and Maximum Likelihood (ML) procedures. The former is implemented
      in Plink and uses a sandwich correction to correct the standard errors for model
      misspecification of ignoring the clustering. The latter is implemented by fast
      linear mixed procedures and models explicitly the familial resemblance. However,
      as it commits to a background model limited to additive genetic and unshared
      environmental effects, it employs a misspecified model for traits with a shared
      environmental component. We considered the performance of the two procedures in
      terms of type I and type II error rates, with correct and incorrect model
      specification in ML. For traits characterized by moderate to large familial
      resemblance, using an ML procedure with a correctly specified model for the
      conditional familial covariance matrix should be the strategy of choice. The
      potential loss in power encountered by the sandwich corrected ULS procedure does
      not outweigh its computational convenience. Furthermore, the ML procedure was
      quite robust under model misspecification in the simulated settings and
      appreciably more powerful than the sandwich corrected ULS procedure. However, to
      correct for the effects of model misspecification in ML in circumstances other
      than those considered here, we propose to use a sandwich correction. We show that
      the sandwich correction can be formulated in terms of the fast ML method. 

PMID- 24916645
TI  - GluD1 is a common altered player in neuronal differentiation from both MECP2
      mutated and CDKL5-mutated iPS cells.
AB  - Rett syndrome is a monogenic disease due to de novo mutations in either MECP2 or
      CDKL5 genes. In spite of their involvement in the same disease, a functional
      interaction between the two genes has not been proven. MeCP2 is a transcriptional
      regulator; CDKL5 encodes for a kinase protein that might be involved in the
      regulation of gene expression. Therefore, we hypothesized that mutations
      affecting the two genes may lead to similar phenotypes by dysregulating the
      expression of common genes. To test this hypothesis we used induced pluripotent
      stem (iPS) cells derived from fibroblasts of one Rett patient with a MECP2
      mutation (p.Arg306Cys) and two patients with mutations in CDKL5 (p.Gln347Ter and
      p.Thr288Ile). Expression profiling was performed in CDKL5-mutated cells and genes
      of interest were confirmed by real-time RT-PCR in both CDKL5- and MECP2-mutated
      cells. The only major change in gene expression common to MECP2- and CDKL5
      mutated cells was for GRID1, encoding for glutamate D1 receptor (GluD1), a member
      of the delta-family of ionotropic glutamate receptors. GluD1 does not form AMPA
      or NMDA glutamate receptors. It acts like an adhesion molecule by linking the
      postsynaptic and presynaptic compartments, preferentially inducing the inhibitory
      presynaptic differentiation of cortical neurons. Our results demonstrate that
      GRID1 expression is downregulated in both MECP2- and CDKL5-mutated iPS cells and
      upregulated in neuronal precursors and mature neurons. These data provide novel
      insights into disease pathophysiology and identify possible new targets for
      therapeutic treatment of Rett syndrome. 

PMID- 24916647
TI  - To disclose, or not to disclose? Context matters.
AB  - Progress in understanding childhood disease using next-generation sequencing
      (NGS) portends vast improvements in the nature and quality of patient care.
      However, ethical questions surrounding the disclosure of incidental findings
      (IFs) persist, as NGS and other novel genomic technologies become the preferred
      tool for clinical genetic testing. Thus, the need for comprehensive management
      plans and multidisciplinary discussion on the return of IFs in pediatric research
      has never been more immediate. The aim of this study is to explore the views of
      investigators concerning the return of IFs in the pediatric oncology research
      context. Our findings reveal at least four contextual themes underlying the
      ethics of when, and how, IFs could be disclosed to participants and their
      families: clinical significance of the result, respect for individual, scope of
      professional responsibilities, and implications for the healthcare/research
      system. Moreover, the study proposes two action items toward anticipatory
      governance of IF in genetic research with children. The need to recognize the
      multiplicity of contextual factors in determining IF disclosure practices,
      particularly as NGS increasingly becomes a centerpiece in genetic research
      broadly, is heightened when children are involved. Sober thought should be given
      to the possibility of discovering IF, and to proactive discussions about
      disclosure considering the realities of young participants, their families, and
      the investigators who recruit them. 

PMID- 24916648
TI  - A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new
      susceptibility loci for myocardial infarction in Japanese.
AB  - Despite considerable progress in preventive and therapeutic strategies,
      myocardial infarction (MI) is one of the leading causes of death throughout the
      world. A total of 55 susceptibility genes have been identified mostly in European
      genome-wide association studies (GWAS). Nevertheless, large-scale GWAS from other
      population could possibly find additional susceptibility loci. To identify as
      many MI susceptibility loci as possible, we performed a large-scale genomic
      analysis in Japanese population. To identify MI susceptibility loci in Japanese,
      we conducted a GWAS using 1666 cases and 3198 controls using the Illumina
      Human610-Quad BeadChip and HumanHap550v3 Genotyping BeadChip. We performed
      replication studies using a total of 11,412 cases and 28,397 controls in the
      Japanese population. Our study identified two novel susceptibility loci for MI:
      PLCL2 on chromosome 3p24.3 (rs4618210:A>G, P = 2.60 * 10(-9), odds ratio (OR) =
      0.91) and AP3D1-DOT1L-SF3A2 on chromosome 19p13.3 (rs3803915:A>C, P = 3.84 * 10(
      9), OR = 0.89). Besides, a total of 14 previously reported MI susceptibility loci
      were replicated in our study. In particular, we validated a strong association on
      chromosome 12q24 (rs3782886:A>G: P = 1.14 * 10(-14), OR = 1.46). Following
      pathway analysis using 265 genes related to MI or coronary artery disease, we
      found that these loci might be involved in the pathogenesis of MI via the
      promotion of atherosclerosis. In the present large-scale genomic analysis, we
      identified PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for MI in the
      Japanese population. Our findings will add novel findings for MI susceptibility
      loci.

PMID- 24916649
TI  - Willingness to pay for genetic testing for inherited retinal disease.
AB  - This paper investigates the willingness of adults with inherited retinal disease
      to undergo and pay for diagnostic genetic testing in three hypothetical scenarios
      and to explore the factors that influence decision making. Fifty patients were
      presented with three scenarios whereby genetic testing provided increasing
      information: confirming the diagnosis and inheritance pattern alone, providing
      additional information on future visual function, and identifying in addition a
      new treatment which could stabilise their condition. Willingness to pay (WTP) was
      elicited using an iterative bidding game. Regression analysis was used to
      investigate the probability of agreeing to and paying for testing. Qualitative
      data were also reviewed to provide a comprehensive understanding of WTP and
      decision making. The majority of participants agreed to undergo genetic testing
      in each of the three scenarios. Scenario 2 was the least acceptable with 78% of
      participants agreeing to genetic testing. The probability of agreeing to genetic
      testing decreased with age. Between 72 and 96% of participants reported a WTP for
      genetic testing. Average WTP was L539, L1516, and L6895 for scenarios 1, 2, and 3
      respectively. Older participants and participants with higher incomes were
      willing to pay more for testing. Qualitative data provided additional detail
      about the rationale behind participants' decisions. The study suggests that
      patients with inherited retinal disease were willing to undergo and to pay for
      diagnostic genetic testing, suggesting that they valued the information it may
      provide. However, several patients preferred not to receive prognostic
      information and were less willing to pay for genetic testing that yielded such
      detail. 

PMID- 24916653
TI  - A new ultrafast superionic Li-conductor: ion dynamics in Li11Si2PS12 and
      comparison with other tetragonal LGPS-type electrolytes.
AB  - We report on a new ultrafast solid electrolyte of the composition Li11Si2PS12,
      which exhibits a higher room-temperature Li ion diffusivity than the present
      record holder Li10GeP2S12. We discuss the high-pressure synthesis and ion
      dynamics of tetragonal Li11Si2PS12, and comparison is made with our
      investigations of related members of the LMePS family, i.e. electrolytes of the
      general formula Li11-xMe2-xP1+xS12 with Me = Ge, Sn : Li10GeP2S12, Li7GePS8,
      Li10SnP2S12. The structure and dynamics were studied with multiple complementary
      techniques and the macroscopic diffusion could be traced back to fast Li ion
      hopping in the crystalline lattice. A clear correlation between the diffusivity
      and the unit cell volume of the LGPS-type electrolytes was observed. 

PMID- 24916651
TI  - Effect of epidural methylprednisolone on post-operative pain and length of
      hospital stay in patients undergoing lumbar microdiscectomy.
AB  - BACKGROUND & AIM: Intraoperative epidural corticosteroids have been used to
      decrease post-operative pain post-discectomy. The objective of this study is to
      assess the efficacy of epidural corticosteroids on post-operative pain and length
      of post-operative hospital stay in patients undergoing unilateral lumbar
      microdiscectomy. METHODS: 150 consecutively treated, comparable patients with
      unilateral lumbar disc herniation were prospectively allocated randomly to
      receive either a sponge soaked in epidural corticosteroids or saline at the end
      of the operative procedure. The intensity of spontaneous pain was quantified by
      using the Oswestry low back pain index pre-operatively, at discharge, at week 1
      follow-up and at 1st month of follow up. At the same intervals, each patient
      underwent the passive straight leg-raising test (PSLRT) and Visual Analogue Scale
      (VAS) testing. The duration of hospital stay, time taken to return to daily life
      activities and quantity of analgesia consumed post-operatively were also
      recorded. RESULTS: The mean hospital stay was 1.3 +/- 0.9 days in the
      corticosteroids group (group 1) compared to 3.2 +/- 1.2 in the control group
      (group 2). The mean interval until return to daily life activities was 6.7 +/-
      2.1 days in group 1 versus 9.6 +/- 4.1 days in group 2. No statistically
      significant difference was measured between the steroid-treated and control
      groups when the data were stratified for sex, age, and site of disc herniation.
      Differences in the OLBI scores were statistically significant at all post
      operative intervals. At baseline (preoperatively), group 1 (DepoMedrolTM group)
      had an average score of 72.3% (+/-2.6%) compared to 74.6% (+/-3.1%) in group 2
      (Control group) (P = 0.45). At discharge, OLBI scores declined to 49.7% (+/-4.5%)
      in group 1 compared to 63.5% (+/-3.9%) in group 2 (P = 0.034). At week 1 follow
      up, OLBI scores further declined to 41.3% (+/-2.9%) in group 1 versus 54.2% (+/
      5.3%) in group 2 (P = 0.014). After one month of follow-up, OLBI scores were
      34.1% (+/-6.7%) in group 1 and 42.6% (+/-4.1%) in group 2 (P = 0.004). Results of
      VAS and PSLRT are also documented in the manuscript. The mean postoperative
      analgesic medications consumed was 15.6 +/- 1.9 mg of morphine equivalent in the
      corticosteroid group versus 10.3 +/- 1.8 mg of morphine equivalent in the control
      group. No complications of treatment occurred in either groups. CONCLUSION:
      Intraoperative application of epidural corticosteroids, Depomedrol, significantly
      reduces post-operative pain, length of post-operative stay and duration to return
      to daily living activities following lumbar discectomy.

PMID- 24916652
TI  - N-staging of oesophageal and junctional carcinoma: is there still a role for EUS
      in patients staged N0 at PET/CT?
AB  - AIM: To assess whether separate endoscopic ultrasound (EUS) lymph node (N)
      staging is still of prognostic value in those staged node negative (N0) at
      combined positron-emission tomography/computed tomography (PET/CT) in patients
      with oesophageal cancer (OC). MATERIALS AND METHODS: One hundred and seventeen
      consecutive patients [median age 67 years; 88 male; 98 cases of adenocarcinoma,
      19 cases of squamous cell carcinoma (SCC)] staged as N0 at PET/CT underwent EUS
      to record tumour (T)- and N-stage. The patients were subsequently separated into
      two groups: EUS N0 (n = 78) and EUS N+ (n = 39). Survival analysis using Kaplan
      Meier and Cox's proportional hazard methods was performed. Primary outcome was
      overall survival from diagnosis. RESULTS: EUS N-stage and EUS N0 versus EUS N+ (p
      = 0.005 and p = 0.001, respectively) were found to be significantly and
      independently associated with survival in two models of multivariate analysis, in
      patients staged N0 at PET/CT. EUS T-stage was significantly associated with
      survival on univariate analysis. CONCLUSION: EUS N-staging still has prognostic
      value in patients staged N0 at PET/CT. There is a significant difference in
      survival between EUS N0 and positive nodal EUS status in those staged N0 at
      PET/CT, suggesting PET/CT is unreliable for local staging. PET/CT and EUS
      continue to have complimentary roles in OC staging.

PMID- 24916650
TI  - Identifying genetic risk variants for coronary heart disease in familial
      hypercholesterolemia: an extreme genetics approach.
AB  - Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial
      hypercholesterolemia (FH), a disorder characterized by coronary heart disease
      (CHD) at young age. We aimed to apply an extreme sampling method to enhance the
      statistical power to identify novel genetic risk variants for CHD in individuals
      with FH. We selected cases and controls with an extreme contrast in CHD risk from
      17,000 FH patients from the Netherlands, whose functional LDLR mutation was
      unequivocally established. The genome-wide association (GWA) study was performed
      on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65
      years for males and 70 years of age for females) using the Illumina HumanHap550K
      chip. In the next stage, two independent samples (one from the Netherlands and
      one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used
      as replication samples. In the initial GWA analysis, we identified 29 independent
      single nucleotide polymorphisms (SNPs) with suggestive associations with
      premature CHD (P<1 * 10(-4)). We examined the association of these SNPs with CHD
      risk in the replication samples. After Bonferroni correction, none of the SNPs
      either replicated or reached genome-wide significance after combining the
      discovery and replication samples. Therefore, we conclude that the genetics of
      CHD risk in FH is complex and even applying an 'extreme genetics' approach we did
      not identify new genetic risk variants. Most likely, this method is not as
      effective in leveraging effect size as anticipated, and may, therefore, not lead
      to significant gains in statistical power.

PMID- 24916654
TI  - Application and recovery of ionic liquids in the preparative separation of four
      flavonoids from Rhodiola rosea by on-line three-dimensional liquid
      chromatography.
AB  - A novel on-line three-dimensional liquid chromatography method was developed to
      separate four main flavonoids from Rhodiola rosea. Ethyl acetate/0.5 mol/L ionic
      liquid 1-butyl-3-methylimidazolium chloride aqueous solution was selected as the
      solvent system. In the first-dimension separation, the target flavonoids were
      entrapped and subsequently desorbed into the second-dimension high-speed
      countercurrent chromatographic column for separation. In the third-dimension
      chromatography, the residual ionic liquid in the four separated flavonoids was
      removed and the used ionic liquid was recovered. As a result, 35.1 mg of compound
      1, 20.4 mg of compound 2, 8.5 mg of compound 3, and 10.6 mg of compound 4 were
      obtained from 1.53 g R. rosea extract. They were identified as rhodiosin,
      rhodionin, herbacetin, and kaempferol, respectively. The recovery of ionic liquid
      reached 99.1% of the initial amount. The results showed that this method is a
      powerful technology for the separation of R. rosea flavonoids and that the ionic
      liquid-based solvent system has advantages over traditional solvent systems in
      renewable and environmentally friendly properties. 

PMID- 24916655
TI  - Expression of Wnt5a during development of anorectal malformations in a rat model
      of prenatal exposure to di(n-butyl) phthalate.
AB  - Mounting evidence has indicated the crucial role of Wnt5a in the embryonic
      development including guts. However, the Wnt5a involvement in the process of
      anorectal malformations (ARMs) remains unclear. In this study, we examined the
      expression of Wnt5a during ARMs development in the offspring of di(n-butyl)
      phthalate (DBP)-treated pregnant rats. During the neonatal period, Wnt5a
      expression was evaluated in the terminal rectum of ARM offspring, non-ARM
      littermates and controls. Using real-time polymerase chain reaction (real-time
      PCR), western-blot analysis and immunohistochemistry approaches, we found a
      significant decrease of Wnt5a expression in DBP-induced ARMs rats. Collectively,
      our results demonstrate the aberrant expression of Wnt5a during anorectal
      development, which suggests that Wnt5a might be involved in DBP-induced ARMs.

PMID- 24916656
TI  - On how many fundamental kinds of cells are present on Earth: looking for
      phylogenetic traits that would allow the identification of the primary lines of
      descent.
AB  - The phylogenetic analyses as far as the identification of the number of domains
      of life is concerned have not reached a clear conclusion. In the attempt to
      improve this circumstance, I introduce the concept that the amino acids codified
      in the genetic code might be of markers with outstanding phylogenetic power. In
      particular, I hypothesise the existence of a biosphere populated, for instance,
      by three groups of organisms having different genetic codes because codifying at
      least a different amino acid. Evidently, these amino acids would mark the
      proteins that are present in the three groups of organisms in an unambiguous way.
      Therefore, in essence, this mark would not be other than the one that we usually
      try to make in the phylogenetic analyses in which we transform the protein
      sequences in phylogenetic trees, for the purpose to identify, for example, the
      domains of life. Indeed, this mark would allow to classify proteins without
      performing phylogenetic analyses because proteins belonging to a group of
      organisms would be recognisable as marked in a natural way by at least a
      different amino acid among the diverse groups of organisms. This
      conceptualisation answers the question of how many fundamental kinds of cells
      have evolved from the Last Universal Common Ancestor (LUCA), as the genetic code
      has unique proprieties that make the codified amino acids excellent phylogenetic
      markers. The presence of the formyl-methionine only in proteins of bacteria would
      mark them and would identify these as domain of life. On the other hand, the
      presence of pyrrolysine in the genetic code of the euryarchaeota would identify
      them such as another fundamental kind of cell evolved from the LUCA. Overall, the
      phylogenetic distribution of formyl-methionine and pyrrolysine would identify at
      least two domains of life--Bacteria and Archaea--but their number might be
      actually four; that is to say, Bacteria, Euryarchaeota, archeobacteria that are
      not euryarchaeota and Eukarya. The usually accepted domains of life represented
      by Bacteria, Archaea and Eukarya are not compatible with the phylogenetic
      distribution of these two amino acids and therefore this last classification
      might be mistaken.

PMID- 24916657
TI  - Genetic code evolution started with the incorporation of glycine, followed by
      other small hydrophilic amino acids.
AB  - We propose that glycine was the first amino acid to be incorporated into the
      genetic code, followed by serine, aspartic and/or glutamic acid-small hydrophilic
      amino acids that all have codons in the bottom right-hand corner of the standard
      genetic code table. Because primordial ribosomal synthesis is presumed to have
      been rudimentary, this stage would have been characterized by the synthesis of
      short, water-soluble peptides, the first of which would have comprised
      polyglycine. Evolution of the code is proposed to have occurred by the
      duplication and mutation of tRNA sequences, which produced a radiation of codon
      assignment outwards from the bottom right-hand corner. As a result of this
      expansion, we propose a trend from small hydrophilic to hydrophobic amino acids,
      with selection for longer polypeptides requiring a hydrophobic core for folding
      and stability driving the incorporation of hydrophobic amino acids into the code.

PMID- 24916658
TI  - Rural and urban disparities in quality of life and health-related behaviors among
      chronically ill patients.
AB  - INTRODUCTION: The purpose of this study was to describe rural and urban
      disparities in quality of life and health-related behaviors among chronically ill
      patients. Additionally, effects of health status and health-related behaviors on
      healthcare utilization were investigated. METHODS: The study included 1239
      chronically ill patients from primary care centers in rural areas (eligible
      patients; response rate: 62.0%). The analyzed group was compared with the urban
      group, homogeneous in respect of gender and age (<i>n</i>=1886). Quality of life
      (QoL) was measured using the World Health Organization Quality of Life Instrument
      Short Form (WHOQoL-Bref). The authors also used the Health Behavior Inventory
      (HBI). RESULTS: Only the results in Domain 4 (Environmental) were higher among
      patients from rural areas (13.6 vs 13.4, <i>p</i>=0.015) within the WHOQoL-Bref.
      Differences between rural and urban areas in the contributors to lower QoL
      referred to such variables as gender, height, body mass, BMI and level of
      healthcare utilization. Results of HBI were higher in patients from urban areas
      (85.0 vs 83.1, <i>p</i><0.001). The differences in factors potentially
      contributing to lower levels of health behavior concerned gender, age, height,
      body mass, BMI, having a partner, number of chronic diseases and level of
      healthcare utilization. The authors observed among the rural patients fewer
      visits of district nurses (12.1 vs 15.3, <i>p</i>=0.003). Odds ratio (OR) for QoL
      in the case of place of residence (rural vs urban) was OR=1.341 (95% CI: 1.067
      1.687). CONCLUSIONS: Higher quality of life may reduce the level of healthcare
      utilization among residents of rural and urban areas. Educational programs,
      promoting health behaviors, should be primarily addressed to rural patients, men,
      younger individuals, patients with a lower number of chronic diseases, and those
      using healthcare services less often.

PMID- 24916659
TI  - The methodological rigor of anticipatory bioethics.

PMID- 24916660
TI  - Informants a potential threat to confidentiality in small studies.
AB  - Providing proper protection of confidentiality, by preventing personal data from
      falling into the hands of third parties, is one of the core responsibilities of
      researchers towards research participants. However, even if researchers do their
      best in this regard, it does not guarantee that breaches of confidentiality will
      be avoided. This paper addresses the case of small qualitative studies, arguing
      that researchers cannot guarantee their informants' confidentiality, since that
      confidentiality may be compromised by actions taken by the informants themselves.
      In order to reduce the risk of this specific threat to confidentiality,
      additional precautions need to be taken. Some potential solutions to the problem
      are suggested and discussed. 

PMID- 24916662
TI  - Discovering functional DNA elements using population genomic information: a proof
      of concept using human mtDNA.
AB  - Identifying the complete set of functional elements within the human genome would
      be a windfall for multiple areas of biological research including medicine,
      molecular biology, and evolution. Complete knowledge of function would aid in the
      prioritization of loci when searching for the genetic bases of disease or
      adaptive phenotypes. Because mutations that disrupt function are disfavored by
      natural selection, purifying selection leaves a detectable signature within
      functional elements; accordingly, this signal has been exploited for over a
      decade through the use of genomic comparisons of distantly related species. While
      this is so, the functional complement of the genome changes extensively across
      time and between lineages; therefore, evidence of the current action of purifying
      selection in humans is essential. Because the removal of deleterious mutations by
      natural selection also reduces within-species genetic diversity within functional
      loci, dense population genetic data have the potential to reveal genomic elements
      that are currently functional. Here, we assess the potential of this approach by
      examining an ultradeep sample of human mitochondrial genomes (n = 16,411). We
      show that the high density of polymorphism in this data set precisely delineates
      regions experiencing purifying selection. Furthermore, we show that the number of
      segregating alleles at a site is strongly correlated with its divergence across
      species after accounting for known mutational biases in human mitochondrial DNA
      (rho = 0.51; P < 2.2 * 10(-16)). These two measures track one another at a
      remarkably fine scale across many loci-a correlation that is purely the result of
      natural selection. Our results demonstrate that genetic variation has the
      potential to reveal with surprising precision which regions in the genome are
      currently performing important functions and likely to have deleterious fitness
      effects when mutated. As more complete human genomes are sequenced, similar power
      to reveal purifying selection may be achievable in the human nuclear genome. 

PMID- 24916661
TI  - Evidence for soft selective sweeps in the evolution of pneumococcal multidrug
      resistance and vaccine escape.
AB  - The multidrug-resistant Streptococcus pneumoniae Taiwan(19F)-14, or PMEN14, clone
      was first observed with a 19F serotype, which is targeted by the heptavalent
      polysaccharide conjugate vaccine (PCV7). However, "vaccine escape" PMEN14
      isolates with a 19A serotype became an increasingly important cause of disease
      post-PCV7. Whole genome sequencing was used to characterize the recent evolution
      of 173 pneumococci of, or related to, PMEN14. This suggested that PMEN14 is a
      single lineage that originated in the late 1980s in parallel with the acquisition
      of multiple resistances by close relatives. One of the four detected serotype
      switches to 19A generated representatives of the sequence type (ST) 320 isolates
      that have been highly successful post-PCV7. A second produced an ST236 19A
      genotype with reduced resistance to beta-lactams owing to alteration of pbp1a and
      pbp2x sequences through the same recombination that caused the change in
      serotype. A third, which generated a mosaic capsule biosynthesis locus, resulted
      in serotype 19A ST271 isolates. The rapid diversification through homologous
      recombination seen in the global collection was similarly observed in the absence
      of vaccination in a set of isolates from the Maela refugee camp in Thailand, a
      collection that also allowed variation to be observed within carriage through
      longitudinal sampling. This suggests that some pneumococcal genotypes generate a
      pool of standing variation that is sufficiently extensive to result in "soft"
      selective sweeps: The emergence of multiple mutants in parallel upon a change in
      selection pressure, such as vaccine introduction. The subsequent competition
      between these mutants makes this phenomenon difficult to detect without deep
      sampling of individual lineages. 

PMID- 24916663
TI  - Israel Medical Association fights to stop legalisation of force feeding prisoners
      on hunger strike.

PMID- 24916664
TI  - Clinical considerations for working with patients with advanced cancer.
AB  - Advanced cancer is a life-limiting condition, but improvements in medical care
      are contributing to longer survival among some patients. As a result, it is
      likely that mental health professionals will be called upon to assist more
      patients with advanced cancer. The present paper reviews the psychological
      literature and from it draws clinical considerations for working with individuals
      affected by advanced cancer. It begins with a brief description of advanced
      cancer and the medical attributes of an advanced cancer diagnosis, and then
      catalogues salient medical, psychological, existential, and interpersonal
      challenges faced by this patient population. The review concludes with
      recommendations for treatment planning including an overview of some of the more
      recently tested and widely available interventions. It is hoped that this review
      will serve as a resource for professionals working with patients affected by
      advanced cancer. 

PMID- 24916665
TI  - Multidisciplinary rehabilitation for chronic widespread musculoskeletal pain:
      results from daily practice.
AB  - INTRODUCTION: Evidence for the efficacy of a multi-component approach for chronic
      widespread musculoskeletal pain (CWP) has been reported, although the effects are
      overall moderate and this approach has rarely been investigated in real life.
      AIM: The aim of the study was to describe the effects of a 15-week
      multidisciplinary pain rehabilitation programme on pain, activities and
      participation in patients with CWP. METHODS: The current retrospective study used
      data which were routinely gathered on all consecutive patients with CWP referred
      to a rehabilitation programme over a 21-month period. The 15-week
      multidisciplinary rehabilitation programme consisted of cognitive behavioural
      therapy and exercise, as well as individual and group sessions with additional
      treatment modalities. Assessments included the Pain Disability Index (PDI), the
      Pain Catastrophizing Scale (PCS), the Multidimensional Pain Inventory (MPI),
      numerical scales for pain and fatigue, the Canadian Occupational Performance
      Measure (COPM), the one-minute stair-climb test and the RAND-36. Paired t-tests
      and Wilcoxon signed-rank tests were carried out to analyse changes over time.
      RESULTS: A total of 165 patients were included [mean age 44.1 (standard deviation
      12.9) years], 143 (87%) women). Discharge data were available for 154 patients
      (93%). All outcomes showed statistically significant improvements between
      admission and discharge (p<0.05), with the largest effect sizes (>1.0) observed
      for the COPM. A longer duration of complaints was associated with less
      improvement in the PDI. DISCUSSION AND CONCLUSION: In daily rehabilitation
      practice, a 15-week multidisciplinary treatment programme for patients with CWP
      showed statistically significant improvements in pain, activities and
      participation over time. Future studies are needed further to substantiate the
      long-term cost-effectiveness, and to identify the patients who benefit the most.

PMID- 24916666
TI  - Association between the oxytocin receptor (OXTR) gene and children's social
      cognition at 18 months.
AB  - At 18 months, children engage in a variety of social behaviors that reflect their
      nascent ability to understand the intentions of other people (e.g. joint
      attention, empathy, cooperation and self-recognition). Although numerous
      contextual factors have been shown to predict social cognition in young children,
      the genetic underpinnings of social-cognitive traits has been understudied in
      this age group. Owing to the known effects of oxytocin on adult social cognition
      and psychopathology, this study hypothesized that variability in the oxytocin
      receptor gene (OXTR) would be associated with social cognition in children at 18
      months. Participants consisted of 350 children (182 males; 168 females) who were
      part of an ongoing longitudinal study that aimed to assess environmental and
      genetic contributions to children's cognitive and socio-emotional functioning. At
      18 months, social cognition was measured using previously validated and
      developmentally sensitive tasks assessing children's joint attention, empathy,
      cooperation and self-recognition. Five potentially functional OXTR variants were
      genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family
      based association design was used to control for population admixture and
      stratification, and additional non-genomic covariates were controlled. Results
      showed that variability in rs11131149 was significantly associated with social
      cognition (P=0.009), with more copies of the major allele related to higher
      social cognition, and more copies of the minor (risk) allele associated with
      lower social cognition. A haplotype consisting of rs11131149-rs2254298 was also
      associated with social cognition (P=0.020). Implications for normative and
      pathological development are discussed, and key areas for future research are
      proposed.

PMID- 24916667
TI  - LncRNA-regulated infection and inflammation pathways associated with pregnancy
      loss: genome wide differential expression of lncRNAs in early spontaneous
      abortion.
AB  - PROBLEM: Spontaneous abortion (SA) occurs before 20 gestational weeks.
      Approximately, half of recurrent SA has no identifiable cause. No report has yet
      been investigated the possible involvement of lncRNA in pregnancy loss. METHOD OF
      STUDY: Sixteen pairs of pregnancies with spontaneous abortions (SA) and induced
      abortions (IA) were studied. Embryonic sacs and decidua were collected for each
      pregnancy. A Human LncRNA Array was employed to profile genomewide lncRNAs, which
      were then validated by RT-PCR. RESULTS: Differentially expressed lncRNAs were
      identified. Biological pathways were categorized into six major groups: infection
      and inflammation, metabolism, signaling and transcriptional regulation, smooth
      muscle contraction, cell process, and coagulation. CONCLUSIONS: Infection and
      inflammation pathways regulated by lncRNAs were determined as the predominant
      pathogenetic factors underlying the SA. Finding that antisense lncRNAs have been
      either up- or down-regulated suggests that they may have both cis- and trans
      regulations.

PMID- 24916668
TI  - Expression analysis of Bombyx mori bidensovirus structural proteins and assembly
      of virus-like particles in insect cells.
AB  - Bombyx mori bidensovirus (BmBDV) is a new designated species of the new genus
      Bidensovirus in the new family Bidnaviridae, which contains two single-stranded
      linear DNAs (VD1 and VD2) and causes the chronic densonucleosis disease of
      silkworm. Previous researches revealed that VD1-ORF3 encodes the major structural
      proteins VPs. In this work, through western blot, we found that VPs expressed
      from 48 h post-inoculation and kept increasing until 120 h post-inoculation in
      midgut of Bombyx mori. In order to further investigate the translation of vp
      gene, the ORFs (vp1 and vp2) of the VP started just up-stream of the first two
      candidate initiation codons were expressed in Sf9 cells by a baculovirus
      expression system. The expression products were purified by gradient density
      centrifugation and analyzed by Western blot and electron microscopy. The results
      showed that the expressions of vp1 yielded three proteins (VP1, VP1', and VP2),
      which are the same with the viral VPs expression in midgut of Bombyx mori, and
      vp2 generated two VPs with the molecular weights of about 51 kDa (VP2) and 37
      kDa. The observation by electron microscopy indicated that these VPs can auto
      assemble into virus-like particles that could not be distinguished from virus
      particles. These findings will provide materials for studying the structure of
      BmBDV and be helpful in the studies on BmBDV-based disease in silkworms. 

PMID- 24916669
TI  - Modeling and analysis of Gleason score 8-10 prostate cancers in the REDUCE study.
AB  - OBJECTIVE: To explore explanations for the numerical imbalance of biopsy-detected
      Gleason 8-10 prostate cancers (PCa) diagnosed in years 3-4 in the dutasteride and
      placebo groups of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE)
      study. METHODS: REDUCE was a 4-year, randomized, double-blind, placebo-controlled
      trial of dutasteride (0.5 mg/d) vs placebo for PCa risk reduction. We modeled the
      incidence of Gleason 8-10 cancer and used logistic regression analysis to
      evaluate the effects of baseline predictors of PCa, as well as post-baseline
      prostate volume at the time of biopsy, on PCa diagnosis. We compared needle
      biopsy Gleason scores with corresponding surgery Gleason scores. All statistical
      tests conducted were 2-sided. RESULTS: Had there been a scheduled biopsy
      occurring only at year 4, we estimated a similar incidence of Gleason 8-10 PCa in
      the dutasteride (n = 45) and placebo (n = 46) groups. Two biopsy Gleason 7
      cancers in the placebo group (n = 150) were upgraded to Gleason 8-10 cancer on
      prostatectomy, and no patients in the dutasteride group (n = 111) were upgraded.
      Logistic regression analysis demonstrated the effect of prostate volume on
      Gleason 8-10 cancer diagnosis. CONCLUSION: Although modeling of REDUCE data
      showed a similar incidence of Gleason 8-10 cancer in the dutasteride and placebo
      groups at year 4, an association between dutasteride and Gleason 8-10 cancer
      cannot be definitely excluded. It is likely that several biases, notably study
      design and prostate size at the time of biopsy, contributed to the numerical
      imbalance in Gleason 8-10 cancers observed between the treatment groups in years
      3-4.

PMID- 24916670
TI  - John Kingsley Lattimer: urologist, ballistics expert, and historian.

PMID- 24916671
TI  - EFIN: predicting the functional impact of nonsynonymous single nucleotide
      polymorphisms in human genome.
AB  - BACKGROUND: Predicting the functional impact of amino acid substitutions (AAS)
      caused by nonsynonymous single nucleotide polymorphisms (nsSNPs) is becoming
      increasingly important as more and more novel variants are being discovered.
      Bioinformatics analysis is essential to predict potentially causal or
      contributing AAS to human diseases for further analysis, as for each genome,
      thousands of rare or private AAS exist and only a very small number of which are
      related to an underlying disease. Existing algorithms in this field still have
      high false prediction rate and novel development is needed to take full advantage
      of vast amount of genomic data. RESULTS: Here we report a novel algorithm that
      features two innovative changes: 1. making better use of sequence conservation
      information by grouping the homologous protein sequences into six blocks
      according to evolutionary distances to human and evaluating sequence conservation
      in each block independently, and 2. including as many such homologous sequences
      as possible in analyses. Random forests are used to evaluate sequence
      conservation in each block and to predict potential impact of an AAS on protein
      function. Testing of this algorithm on a comprehensive dataset showed significant
      improvement on prediction accuracy upon currently widely-used programs. The
      algorithm and a web-based application tool implementing it, EFIN (Evaluation of
      Functional Impact of Nonsynonymous SNPs) were made freely available
      (http://paed.hku.hk/efin/) to the public. CONCLUSIONS: Grouping homologous
      sequences into different blocks according to the evolutionary distance of the
      species to human and evaluating sequence conservation in each group independently
      significantly improved prediction accuracy. This approach may help us better
      understand the roles of genetic variants in human disease and health.

PMID- 24916672
TI  - Crying and suicidal, but not depressed. Pseudobulbar affect in multiple sclerosis
      successfully treated with valproic acid: Case report and literature review.
AB  - OBJECTIVE: Pseudobulbar affect/emotional incontinence is a potentially disabling
      condition characterized by expressions of affect or emotions out of context from
      the normal emotional basis for those expressions. This condition can result in
      diagnostic confusion and unrelieved suffering when clinicians interpret the
      emotional expressions at face value. In addition, the nomenclature, etiology, and
      treatment for this condition remain unclear in the medical literature. METHOD: We
      report the case of a 60-year-old woman with multiple sclerosis who was referred
      to an inpatient psychiatry unit with complaints of worsening depression along
      with hopelessness, characterized by unrelenting crying. Our investigation showed
      that her symptoms were caused by pseudobulbar affect/emotional incontinence
      stemming from multiple sclerosis. RESULTS: The patient's history of multiple
      sclerosis and the fact that she identified herself as depressed only because of
      her incessant crying suggested that her symptoms might be due to the multiple
      sclerosis rather than to a depressive disorder. Magnetic resonance imaging
      demonstrated a new plaque consistent with multiple sclerosis lateral to her
      corpus callosum. Her symptoms resolved completely within three days on valproic
      acid but returned after she was cross-tapered to dextromethorphan plus quinidine,
      which is the FDA-approved treatment for this condition. SIGNIFICANCE OF RESULTS:
      This case provides important additional information to the current literature on
      pseudobulbar affect/emotional incontinence. The existing literature suggests a
      selective serotonin reuptake inhibitor (SSRI) and dextromethorphan/quinidine
      (Nuedexta) as first-line treatments; however, our patient was taking an SSRI at
      the time of presentation without appreciable benefit, and her symptoms responded
      to valproic acid but not to the dextromethorphan/quinidine. In addition, the case
      and the literature review suggest that the current nomenclature for this
      constellation of symptoms can be misleading.

PMID- 24916673
TI  - Residual lower esophageal sphincter pressure as a prognostic factor in the
      pneumatic balloon treatment of achalasia.
AB  - BACKGROUND AND AIMS: Pneumatic balloon dilatation (PD) is a mainstay in achalasia
      treatment. The aim of this study was to identify predictive factors for
      successful treatment. METHODS: We retrospectively reviewed 76 patients with a
      diagnosis of achalasia who underwent PD from June 2010 to May 2013. Clinical
      symptoms were assessed using Eckardt score and manometry data were analyzed using
      resting and relaxation pressure (4sIRP) of lower esophageal sphincter (LES) and
      the distal contractile integral (DCI), which was calculated for 10 s from the
      start of deglutition between the upper margin of the LES and lower margin of
      upper esophageal contraction. Patients with achalasia were classified into three
      groups based on the Chicago classification. RESULTS: Among 76 patients, 52
      patients received PD, and the treatment was unsuccessful in 9 patients (6 in
      class I and 3 in class III). When comparing prognostic factors between successful
      and unsuccessful treatment groups, the mean value for 4sIRP in the unsuccessful
      treatment group was significantly lower than that in the successful treatment
      group (P < 0.05). However, no difference was noticed in resting LES pressure,
      DCI, age, and sex. Furthermore, a lower mean value of 4sIRP was significantly
      related to unsuccessful treatment of achalasia (odds ratio, 1.092; 95% confidence
      interval, 1.001-1.191) even after adjustment for a series of confounding factors.
      CONCLUSIONS: Lower 4sIRP may be a prognostic indicator for poor treatment outcome
      after PD.

PMID- 24916674
TI  - Biallelic germline and somatic mutations in malignant mesothelioma: multiple
      mutations in transcription regulators including mSWI/SNF genes.
AB  - We detected low levels of acetylation for histone H3 tail lysines in malignant
      mesothelioma (MM) cell lines resistant to histone deacetylase inhibitors. To
      identify the possible genetic causes related to the low histone acetylation
      levels, whole-exome sequencing was conducted with MM cell lines established from
      eight patients. A mono-allelic variant of BRD1 was common to two MM cell lines
      with very low acetylation levels. We identified 318 homozygous protein-damaging
      variants/mutations (18-78 variants/mutations per patient); annotation analysis
      showed enrichment of the molecules associated with mammalian SWI/SNF (mSWI/SNF)
      chromatin remodeling complexes and co-activators that facilitate initiation of
      transcription. In seven of the patients, we detected a combination of variants in
      histone modifiers or transcription factors/co-factors, in addition to variants in
      mSWI/SNF. Direct sequencing showed that homozygous mutations in SMARCA4, PBRM1
      and ARID2 were somatic. In one patient, homozygous germline variants were
      observed for SMARCC1 and SETD2 in chr3p22.1-3p14.2. These exhibited extended
      germline homozygosity and were in regions containing somatic mutations, leading
      to a loss of BAP1 and PBRM1 expression in MM cell line. Most protein-damaging
      variants were heterozygous in normal tissues. Heterozygous germline variants were
      often converted into hemizygous variants by mono-allelic deletion, and were
      rarely homozygous because of acquired uniparental disomy. Our findings imply that
      MM might develop through the somatic inactivation of mSWI/SNF complex subunits
      and/or histone modifiers, including BAP1, in subjects that have rare germline
      variants of these transcription regulators and/or transcription factors/co
      factors, and in regions prone to mono-allelic deletion during oncogenesis. 

PMID- 24916676
TI  - Caries management pathways preserve dental tissues and promote oral health.
AB  - In May 2012, cariologists, dentists, representatives of dental organizations,
      manufacturers, and third party payers from several countries, met in
      Philadelphia, Pennsylvania, to define a common mission; goals and strategic
      approaches for caries management in the 21th century. The workshop started with
      an address by Mr. Stanley Bergman, CEO of Henry Schein Inc. which focused on the
      imperative for change in academia, clinical practice, and public health. For
      decades, new scientific evidence on caries and how it should be managed have been
      discussed among experts in the field. However, there has been some limited
      change, except in some Scandinavian countries, in the models of caries management
      and reimbursement which have been heavily skewed toward 'drilling and filling'.
      There is no overall agreement on a caries' case definition or on when to
      surgically intervene. The participants in the workshop defined a new mission for
      all caries management approaches, both conventional and new. The mission of each
      system should be to preserve the tooth structure, and restore only when
      necessary. This mission marks a pivotal line for judging when to surgically
      intervene and when to arrest or remineralize early noncavitated lesions. Even
      when restorative care is necessary, the removal of hard tissues should be lesion
      focused and aim to preserve, as much as possible, sound tooth structure.
      Continuing management of the etiological factors of caries and the use of science
      based preventive regimens also will be required to prevent recurrence and re
      restoration. These changes have been debated for over a decade. The Caries
      Management Pathways includes all systems and philosophies, conventional and new,
      of caries management that can be used or modified to achieve the new mission. The
      choice of which system to use to achieve the mission of caries management is left
      to the users and should be based on the science supporting each approach or
      philosophy, experience, utility, and ease of use. This document also presents a
      new 'Caries Management Cycle' that should be followed regardless of which
      approach is adopted for caries prevention, detection, diagnosis, and treatment.
      To aid success in the adoption of the new mission, a new reimbursement system
      that third party payers may utilize is proposed (for use by countries other than
      Scandinavian countries or other countries where such systems already exist). The
      new reimbursement/incentive model focuses on the mission of preservation of tooth
      structure and outcomes of caries management. Also described, is a research agenda
      to revitalize research on the most important and prevalent world-wide human
      disease. The alliance of major dental organizations and experts that started in
      Philadelphia will hopefully propel over the next months and years, a change in
      how caries is managed by dentists all over the world. A new mission has been
      defined and it is time for all oral health professionals to focus on the
      promotion of oral health and preservation of sound teeth rather than counting the
      number of surgical restorative procedures provided. 

PMID- 24916677
TI  - International Caries Detection and Assessment System (ICDAS) and its
      International Caries Classification and Management System (ICCMS) - methods for
      staging of the caries process and enabling dentists to manage caries.
AB  - OBJECTIVES: The aim of this article is to provide an overview of the
      International Caries Detection and Assessment System (ICDAS) and its associated
      International Caries Classification and Management System (ICCMS(TM) ), explain
      the evolution of these systems over the past decade and outline how they are
      being used for staging of the caries process in order to enable dentists to
      manage caries appropriately. METHODS: the article outlines and references the key
      steps in development of these systems. RESULTS: ICDAS employs an evidence-based
      and preventively oriented approach, is a detection and assessment system
      classifying stages of the caries process on the basis of histological extent and
      activity, is designed for use in the four domains of clinical practice,
      education, research and public health and provides all stakeholders with a common
      language for staging caries. Over a decade ICDAS has evolved to comprise a number
      of approved, compatible 'formats', supports decision making at both individual
      and public health levels and has generated the ICCMS(TM) to enable improved long
      term caries outcomes. A range of further developments are in train, to assist
      with information capture and making clinical systems simpler and more practice
      friendly. CONCLUSION: ICDAS provides flexible and increasingly internationally
      adopted methods for classifying stages of the caries process and the activity
      status of lesions which can be incorporated into the ICCMS(TM) . The ICCMS(TM)
      provides options to enable dentists to integrate and synthesize tooth and patient
      information, including caries risk status, in order to plan, manage and review
      caries in clinical and public health practice.

PMID- 24916675
TI  - A flavonoid 3-O-glucoside:2"-O-glucosyltransferase responsible for terminal
      modification of pollen-specific flavonols in Arabidopsis thaliana.
AB  - Flavonol 3-O-diglucosides with a 1->2 inter-glycosidic linkage are representative
      pollen-specific flavonols that are widely distributed in plants, but their
      biosynthetic genes and physiological roles are not well understood. Flavonoid
      analysis of four Arabidopsis floral organs (pistils, stamens, petals and calyxes)
      and flowers of wild-type and male sterility 1 (ms1) mutants, which are defective
      in normal development of pollen and tapetum, showed that kaempferol/quercetin 3-O
      beta-d-glucopyranosyl-(1->2)-beta-d-glucopyranosides accumulated in Arabidopsis
      pollen. Microarray data using wild-type and ms1 mutants, gene expression patterns
      in various organs, and phylogenetic analysis of UDP-glycosyltransferases (UGTs)
      suggest that UGT79B6 (At5g54010) is a key modification enzyme for determining
      pollen-specific flavonol structure. Kaempferol and quercetin 3-O-glucosyl-(1->2)
      glucosides were absent from two independent ugt79b6 knockout mutants. Transgenic
      ugt79b6 mutant lines transformed with the genomic UGT79B6 gene had the same
      flavonoid profile as wild-type plants. Recombinant UGT79B6 protein converted
      kaempferol 3-O-glucoside to kaempferol 3-O-glucosyl-(1->2)-glucoside. UGT79B6
      recognized 3-O-glucosylated/galactosylated anthocyanins/flavonols but not 3,5- or
      3,7-diglycosylated flavonoids, and prefers UDP-glucose, indicating that UGT79B6
      encodes flavonoid 3-O-glucoside:2"-O-glucosyltransferase. A UGT79B6-GUS fusion
      showed that UGT79B6 was localized in tapetum cells and microspores of developing
      anthers. 

PMID- 24916678
TI  - Caries management by risk assessment.
AB  - Caries disease is multifactorial. Whether caries disease will be expressed and
      damage dental hard tissue is dependent on the patient's own unique make-up of
      pathogenic risk factors and protective factors. Objectives This manuscript will
      review the science of managing caries disease based on assessing caries risk.
      Methods The caries balance/imbalance model and a practical caries risk assessment
      procedure for patients aged 6 years through adult will illustrate how treatment
      options can be based on caries risk. Results Neither the forms nor the clinical
      protocols are meant to imply there is currently only one correct way this can be
      achieved, rather are used in this manuscript as examples only. Conclusions It is
      important to have the forms and protocols simple and easy to understand when
      implementing caries management by risk assessment into clinical practice. The
      science of CAMBRA based on the caries balance/imbalance model was reviewed and an
      example protocol was presented. 

PMID- 24916679
TI  - Risk assessment - can we achieve consensus?
AB  - OBJECTIVE: The object of this conference paper was to review and discuss caries
      risk assessment in general practice from the questions i) 'Why', ii) 'When', and
      iii) 'How'. METHOD: Narrative review. RESULTS: i) Patient caries risk assessment
      is the basic component in the decision-making process for adequate prevention and
      management of dental caries and for determination of individual recall intervals.
      ii) Caries risk assessment should always be performed at a child's first dental
      visit and then regularly throughout life, and especially when social or medical
      life events are occurring. iii) There are several risk assessment methods and
      models available for but the evidence for their validity is limited. Although
      there is no clearly superior method for predicting future caries, the use of
      structured protocols combining socioeconomy, behavior, general health, diet, oral
      hygiene routines, clinical data, and salivary tests or computer-based systems are
      considered best clinical practice. The accuracy ranges between 60% and 90%,
      depending on age. Caries risk assessment is more effective in the selection of
      patients at low risk than those with high caries risk. CONCLUSION: As evidence
      suggests that past caries experience is far from ideal but the most important
      single risk component for more caries at all ages, any clinical sign of likely
      active demineralization on smooth, occlusal, and proximal tooth surfaces should
      be taken as a signal for the implementation of individually designed preventive
      and disease management measures.

PMID- 24916680
TI  - The Caries Assessment and Treatment (CAST) instrument.
AB  - OBJECTIVES: To describe the 'Caries Assessment Spectrum and Treatment' (CAST)
      instrument, its origin and content, and to provide an example of how results can
      be reported. METHODS: The CAST instrument covers the complete range of stages of
      carious lesion progression: from no carious lesion, through caries protection
      (sealant) and lesion care (restoration) to lesions in enamel and dentine, the
      advanced stages of carious lesion progression in pulpal and its consequences on
      tooth-surrounding tissue and tooth loss due to caries. Using the RAND modified e
      Delphi consensus method two independent panels, comprising a total of 56
      epidemiologists from 27 countries, determined the face and content validity of
      CAST. Panellists assessed 17 statements related to the content, description,
      suitability and international use of CAST. Agreement of 75% or higher was
      required for reaching consensus on a statement. Construct validity and
      reliability testing of CAST have been carried out, but results are not yet
      available. RESULTS: All 17 statements were approved by the panellists, who found
      the RAND modified e-Delphi consensus method suitable for achieving consensus. The
      CAST codes were ordered hierarchically. External validity was obtained. Reporting
      using CAST can be performed for orally healthy dentitions and those having
      morbidity and mortality. A DMF score can easily be calculated from the CAST
      codes, thereby enabling retention of the use of existing DMF scores. CONCLUSION:
      The CAST instrument for use in epidemiological surveys is very promising. Face
      and content validation is obtained. Construct validity and reliability testing
      will be completed soon. A structure for reporting results in a comprehensive,
      pragmatic and easily understood way is being developed.

PMID- 24916681
TI  - Preface. Caries management pathways (CaMPs).

PMID- 24916682
TI  - Restriction site-associated DNA sequencing, genotyping error estimation and de
      novo assembly optimization for population genetic inference.
AB  - Restriction site-associated DNA sequencing (RADseq) provides researchers with the
      ability to record genetic polymorphism across thousands of loci for nonmodel
      organisms, potentially revolutionizing the field of molecular ecology. However,
      as with other genotyping methods, RADseq is prone to a number of sources of error
      that may have consequential effects for population genetic inferences, and these
      have received only limited attention in terms of the estimation and reporting of
      genotyping error rates. Here we use individual sample replicates, under the
      expectation of identical genotypes, to quantify genotyping error in the absence
      of a reference genome. We then use sample replicates to (i) optimize de novo
      assembly parameters within the program Stacks, by minimizing error and maximizing
      the retrieval of informative loci; and (ii) quantify error rates for loci,
      alleles and single-nucleotide polymorphisms. As an empirical example, we use a
      double-digest RAD data set of a nonmodel plant species, Berberis alpina,
      collected from high-altitude mountains in Mexico.

PMID- 24916683
TI  - ATV riding and helmet use among youth aged 12-17 years, USA, 2011: results from
      the YouthStyles survey.
AB  - BACKGROUND: National estimates of all-terrain vehicle (ATV) riding patterns among
      youth in the USA are lacking. METHODS: We analysed the 2011 YouthStyles survey to
      estimate the proportion of 12-17 year olds in the USA who had ridden an ATV at
      least once during the past 12 months and summarise their patterns of helmet use.
      RESULTS: Of the 831 youth respondents, an estimated 25% reported riding an ATV at
      least once during the past year. The proportion of youth living outside of a
      Metropolitan Statistical Area who reported riding an ATV was twice that of those
      living inside of a Metropolitan Statistical Area. Males and females reported
      similar proportions of riding at least once during the past year, but among
      riders, the proportion of males who rode >=6 times was triple that of females.
      Only 45% of riders reported always wearing a helmet, and 25% reported never
      wearing a helmet. The most frequent riders had the lowest consistent helmet use,
      with 8 of 10 youth who rode >=6 times during the past year not always wearing a
      helmet. CONCLUSIONS: ATV riding appears to remain popular among youth in the USA,
      particularly in rural areas, and consistent helmet use while riding is low. A
      more thorough understanding of gender differences in ATV riding patterns among
      youth and perceived risks and benefits of both safe and unsafe riding practices
      might help inform future ATV injury prevention efforts.

PMID- 24916684
TI  - Engagement with the TeenDrivingPlan and diversity of teens' supervised practice
      driving: lessons for internet-based learner driver interventions.
AB  - OBJECTIVE: Inexperienced, less-skilled driving characterises many newly licensed
      drivers and contributes to high crash rates. A randomised trial of
      TeenDrivingPlan (TDP), a new learner driver phase internet-based intervention,
      demonstrated effectiveness in improving safety relevant, on-road driving
      behaviour, primarily through greater driving practice diversity. To inform future
      learner driver interventions, this analysis examined TDP use and its association
      with practice diversity. DESIGN: Posthoc analysis of data from teen/parent dyads
      (n=107), enrolled early in learner phase and assigned to treatment arm in
      randomised trial. METHODS: Inserted software beacons captured TDP use data.
      Electronic surveys completed by parents and teens assessed diversity of practice
      driving and TDP usability ratings at 24 weeks (end of study period). RESULTS:
      Most families (84%) used TDP early in the learner period; however, the number of
      TDP sessions in the first week was three times higher among dyads who achieved
      greater practice diversity than those with less. By week five many families still
      engaged with TDP, but differences in TDP use could not be detected between
      families with high versus low practice diversity. Usability was not a major issue
      for this sample based on largely positive user ratings. CONCLUSIONS: An engaging
      internet-based intervention, such as TDP, can support families in achieving high
      practice diversity. Future learner driver interventions should provide important
      information early in the learner period when engagement is greatest, encourage
      continued learning as part of logging practice drives, and incorporate monitoring
      software for further personalisation to meet family needs. TRIAL REGISTRATION:
      NCT01498575.

PMID- 24916685
TI  - Trends in fall-related injuries among older adults treated in emergency
      departments in the USA.
AB  - To examine national trends in fall-related injuries among older adults treated in
      emergency departments (ED) and project these injuries until the year 2030. The
      Web-based Injury Statistics Query and Reporting System was used to generate data
      on fall-related injuries treated in ED. Joinpoint regression analysis was used to
      examine the average annual change in injury rates over time. Fall-related injury
      and hospitalisation rates increased on average by 2% (95% CI 1.5% to 2.7%) and by
      4% (95% CI 2.9% to 5.0%) per year, respectively. Assuming the increase in fall
      related injury rates remains unchanged, the number of fall-related injuries may
      increase to 5.7 million by the year 2030. Fall-related injuries among older
      adults treated in ED increased in the USA during the study period. Moreover, a
      marked increase in the number of these injuries may occur over the next decades. 

PMID- 24916686
TI  - Safer cycling in the urban road environment: study approach and protocols guiding
      an Australian study.
AB  - BACKGROUND: Much of the research into cyclist safety in Australia has focused on
      behaviour with less focus on the impact of the urban transport environment on
      cyclist safety. A greater understanding of the urban transport system and the
      improvements needed to create a safer cycling environment are essential if
      cyclists are to be safe and increased cycling participation targets are to be
      achieved. The proposed study will use existing cyclist crash data along with
      unique cyclist exposure data to develop road infrastructure prototypes that
      improve cyclists' safety and evaluate the effectiveness of these prototypes in a
      cycling simulator. METHODS AND DESIGN: This study will be conducted in two
      Australian cities namely Perth and Melbourne as both cities have policies that
      strongly advocate cycling. Two methods of data collection will be employed: (1)
      in-depth crash investigations of injured cyclists; and (2) video footage of
      cyclist exposure through a naturalistic cycling study of non-injured cyclists.
      The findings from these two methods will be used to develop new urban road design
      prototypes which will be tested with a sample of cyclists and motorists in safe
      environment namely, a cycling simulator and a driving simulator. DISCUSSION: By
      designing and evaluating safer environments for cyclists, this study will
      identify solutions that reduce the risk of road trauma and importantly, support
      this alternative mode of transport and thereby contribute to a reduction in
      traffic-related emissions and pollution and enhance sustainable economic and
      social connectivity.

PMID- 24916687
TI  - World Cup's extended pub opening hours make no sense.

PMID- 24916689
TI  - Systematic review of screening for trisomy 21 in twin pregnancies in first
      trimester combining nuchal translucency and biochemical markers: a meta-analysis.
AB  - AIM: This article is a systematic review of the literature to establish the
      detection rate and false-positive rate of the combined test for the screening of
      trisomy 21 in twins. MATERIAL AND METHODS: We conducted a literature search
      (MEDLINE, EMBASE and ScienceDirect and Cochrane) to identify studies between 1995
      and 2013 that provided data on the combined test in twins. Selected studies
      included data on maternal age, number of fetuses affected by Down syndrome, test
      strategy, sensitivity and specificity of the test. RESULTS: The combined test in
      twins had a pooled sensitivity of 0.893 [95% confidence interval (CI) 0.797
      0.947] and a pooled specificity of 0.946 (95% CI 0.933-0.957). The performance of
      the test was good (summary receiver operating characteristic area under the
      curve: 0.817). In dichorionic twins, sensitivity and specificity were 0.862 (95%
      CI 0.728-0.936) and 0.952 (95% CI 0.942-0.96), respectively. In monochorionic
      twins, the sensitivity and specificity were 0.874% (95% CI 0.526-0.977) and
      0.954% (95% CI 0.943-0.963), respectively. CONCLUSIONS: The results of this meta
      analysis show that the accumulative evidence on the performance of the combined
      test in twin pregnancies is good. Nowadays, it seems to be the best first
      trimester screening test available for twin pregnancies.

PMID- 24916688
TI  - Mononuclear cells from dedifferentiation of mouse myotubes display remarkable
      regenerative capability.
AB  - Certain lower organisms achieve organ regeneration by reverting differentiated
      cells into tissue-specific progenitors that re-enter embryonic programs. During
      muscle regeneration in the urodele amphibian, postmitotic multinucleated skeletal
      myofibers transform into mononucleated proliferating cells upon injury, and a
      transcription factor-msx1 plays a role in their reprograming. Whether this
      powerful regeneration strategy can be leveraged in mammals remains unknown, as it
      has not been demonstrated that the dedifferentiated progenitor cells arising from
      muscle cells overexpressing Msx1 are lineage-specific and possess the same potent
      regenerative capability as their amphibian counterparts. Here, we show that
      ectopic expression of Msx1 reprograms postmitotic, multinucleated, primary mouse
      myotubes to become proliferating mononuclear cells. These dedifferentiated cells
      reactivate genes expressed by embryonic muscle progenitor cells and generate only
      muscle tissue in vivo both in an ectopic location and inside existing muscle.
      More importantly, distinct from adult muscle satellite cells, these cells appear
      both to fuse with existing fibers and to regenerate myofibers in a robust and
      time-dependent manner. Upon transplantation into a degenerating muscle, these
      dedifferentiated cells generated a large number of myofibers that increased over
      time and replenished almost half of the cross-sectional area of the muscle in
      only 12 weeks. Our study demonstrates that mammals can harness a muscle
      regeneration strategy used by lower organisms when the same molecular pathway is
      activated.

PMID- 24916691
TI  - Abstracts of the IX Congresso Sindem: Italian Association for the study of
      Dementia linked to the Italian Neurological Society (SIN), March 13-15, 2014,
      Florence, Italy.

PMID- 24916690
TI  - Surgical site infections following coronary artery bypass graft procedures: 10
      years of surveillance data.
AB  - BACKGROUND: Surgical site infections following coronary artery bypass graft
      (CABG) procedures pose substantial burden on patients and healthcare systems.
      This study aims to describe the incidence of surgical site infections and
      causative pathogens following CABG surgery over the period 2003-2012, and to
      identify risk factors for complex sternal site infections. METHODS: Routine
      computerised surveillance data were collected from three public hospitals in
      Queensland, Australia in which CABG surgery was performed between 2003 and 2012.
      Surgical site infection rates were calculated by types of infection
      (superficial/complex) and incision sites (sternal/harvest sites). Patient and
      procedural characteristics were evaluated as risk factors for complex sternal
      site infections using a logistic regression model. RESULTS: There were 1,702
      surgical site infections (518 at sternal sites and 1,184 at harvest sites)
      following 14,546 CABG procedures performed. Among 732 pathogens isolated,
      Methicillin-sensitive Staphylococcus aureus accounted for 28.3% of the isolates,
      Pseudomonas aeruginosa 18.3%, methicillin-resistant Staphylococcus aureus 14.6%,
      and Enterobacter species 6.7%. Proportions of Gram-negative bacteria elevated
      from 37.8% in 2003 to 61.8% in 2009, followed by a reduction to 42.4% in 2012.
      Crude rates of complex sternal site infections increased over the reporting
      period, ranging from 0.7% in 2004 to 2.6% in 2011. Two factors associated with
      increased risk of complex sternal site infections were identified: patients with
      an ASA (American Society of Anaesthesiologists) score of 4 or 5 (reference score
      of 3, OR 1.83, 95% CI 1.36-2.47) and absence of documentation of antibiotic
      prophylaxis (OR 2.03, 95% CI 1.12-3.69). CONCLUSIONS: Compared with previous
      studies, our data indicate the importance of Gram-negative organisms as causative
      agents for surgical site infections following CABG surgery. An increase in
      complex sternal site infection rates can be partially explained by the increasing
      proportion of patients with more severe underlying disease.

PMID- 24916692
TI  - Increasing stability of antibody via antibody engineering: stability engineering
      on an anti-hVEGF.
AB  - Antibody stability is very important for expression, activity, specificity, and
      storage. This knowledge of antibody structure has made it possible for a computer
      aided molecule design to be used to optimize and increase antibody stability.
      Many computational methods have been built based on knowledge or structure,
      however, a good integrated engineering system has yet to be developed that
      combines these methods. In the current study, we designed an integrated computer
      aided engineering protocol, which included several successful methods. Mutants
      were designed considering factors that affected stability and multiwall filter
      screening was used to improve the design accuracy. Using this protocol, the
      thermo-stability of an anti-hVEGF antibody was significantly improved. Nearly 40%
      of the single-point mutants proved to be more stable than the parent antibody and
      most of the mutations could be stacked effectively. The T50 also improved about 7
      degrees C by combinational mutation of seven sites in the light chain and three
      sites in the heavy chain. Data indicate that the protocol is an effective method
      for optimization of antibody structure, especially for improving thermo
      stability. This protocol could also be used to enhance the stability of other
      antibodies.

PMID- 24916693
TI  - TP53 mutations and lung cancer: not all mutations are created equal.
AB  - Mutations in TP53 are common in non-small cell lung cancer. Apart from the loss
      of tumor-suppressor functions, TP53 mutations may result in gain of function
      favoring cellular proliferation, inhibition of apoptosis, and genomic
      instability. Some TP53 mutations are more likely to affect the course of the
      disease than others.

PMID- 24916694
TI  - Differences in the transcriptional response to fulvestrant and estrogen
      deprivation in ER-positive breast cancer.
AB  - PURPOSE: Endocrine therapies include aromatase inhibitors and the selective
      estrogen receptor (ER) downregulator fulvestrant. This study aimed to determine
      whether the reported efficacy of fulvestrant over anastrozole, and high- over low
      dose fulvestrant, reflect distinct transcriptional responses. EXPERIMENTAL
      DESIGN: Global gene expression profiles from ERalpha-positive breast carcinomas
      before and during presurgical treatment with fulvestrant (n = 22) or anastrozole
      (n = 81), and corresponding in vitro models, were compared. Transcripts
      responding differently to fulvestrant and estrogen deprivation were identified
      and integrated using Gene Ontology, pathway and network analyses to evaluate
      their potential significance. RESULTS: The overall transcriptional response to
      fulvestrant and estrogen deprivation was correlated (r = 0.61 in presurgical
      studies, r = 0.87 in vitro), involving downregulation of estrogen-regulated and
      proliferation-associated genes. The transcriptional response to fulvestrant was
      of greater magnitude than estrogen deprivation (slope = 0.62 in presurgical
      studies, slope = 0.63 in vitro). Comparative analyses identified 28 genes and 40
      Gene Ontology categories affected differentially by fulvestrant. Seventeen
      fulvestrant-specific genes, including CAV1/2, SNAI2, and NRP1, associated with
      ERalpha, androgen receptor (AR), and TP53, in a network regulating cell cycle,
      death, survival, and tumor morphology. Eighteen genes responding differently to
      fulvestrant specifically predicted antiproliferative response to fulvestrant, but
      not anastrozole. Transcriptional effects of low-dose fulvestrant correlated with
      high-dose treatment, but were of lower magnitude (ratio = 0.29). CONCLUSIONS: The
      transcriptional response to fulvestrant has much in common with estrogen
      deprivation, but is stronger with distinctions potentially attributable to arrest
      of estrogen-independent ERalpha activity and involvement of AR signaling. Genes
      responding differently to fulvestrant may have predictive utility. These data are
      consistent with the clinical efficacy of fulvestrant versus anastrozole and
      higher dosing regimens.

PMID- 24916695
TI  - CLIC4, ERp29, and Smac/DIABLO derived from metastatic cancer stem-like cells
      stratify prognostic risks of colorectal cancer.
AB  - PURPOSE: Cancer stem-like cells have been well accepted to be involved in
      recurrence and metastasis of cancers, but the prognostic potential of biomarkers
      integrating with metastasis and cancer stem-like cells for colorectal cancer is
      unclear. EXPERIMENTAL DESIGN: We identified three proteins, CLIC4, ERp29, and
      Smac/DIABLO, from metastatic cancer stem-like cells of colorectal cancer and
      verified the proteins' role in metastatic behaviors. The proteins were detected
      by IHC in colorectal cancer tumors and matched colonic mucosa from patients with
      colorectal cancer who underwent radical surgery in the training cohort. The
      associations between proteins expression levels and five-year disease-specific
      survival (DSS) were evaluated to predict the survival probability in the training
      cohort of 421 cases and the validation cohort of 228 cases. RESULTS: A three
      protein panel including CLIC4, ERp29, and Smac/DIABLO, which was generated from
      multivariate analysis by excluding clinicopathologic characteristics from the
      training cohort, distinguished patients with colorectal cancer into very low-,
      low-, middle-, and high-risk groups with significant differences in five-year DSS
      probability (88.6%, 63.3%, 30.4%, 11.4%; P < 0.001). The panel is independent
      from tumor-node-metastasis staging system and histologic grading to predict
      prognosis, and also enables classification of validation cohort into four risk
      stratifications (five-year DSS probability is 98.2%, 80.2%, 25.6%, and 2.7%; P <
      0.001). CONCLUSIONS: CLIC4, ERp29, and Smac/DIABLO integrated into a novel panel
      based on cancer stem-like cells in association with metastasis stratify the
      prognostic risks of colorectal cancer. Prediction of risks with molecular markers
      will benefit clinicians to make decisions of individual management with
      postoperative colorectal cancer patients.

PMID- 24916696
TI  - Twisting and ironing: doxorubicin cardiotoxicity by mitochondrial DNA damage.
AB  - Anthracyclines are active clinical agents that have multiple mechanisms of
      cytotoxicity. Cardiotoxicity by anthracyclines limits the therapeutic potential
      of these agents, but mechanisms leading to cardiotoxicity remain controversial.
      Transgenic mice that lack mitochondrial topoisomerase I are hypersensitive to
      doxorubicin cardiotoxicity, providing support for cardiotoxicity arising from
      damage of mitochondrial DNA.

PMID- 24916698
TI  - Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific
      breast and ovarian cancer.
AB  - PURPOSE: Lymphocytic infiltration of tumors predicts improved survival in
      patients with breast cancer. Previous studies have suggested that this survival
      benefit is confined predominantly to the basal-like subtype. Immune infiltration
      in ovarian tumors is also associated with improved prognosis. Currently, it is
      unclear what aspects of the immune response mediate this improved outcome.
      EXPERIMENTAL DESIGN: Using The Cancer Genome Atlas mRNA-seq data and a large
      microarray dataset, we evaluated adaptive immune gene expression by genomic
      subtype in breast and ovarian cancer. To investigate B-cells observed to be
      prognostic within specific subtypes, we developed methods to analyze B-cell
      population diversity and degree of somatic hypermutation (SHM) from B-cell
      receptor (BCR) sequences in mRNA-seq data. RESULTS: Improved metastasis
      free/progression-free survival was correlated with B-cell gene expression
      signatures, which were restricted mainly to the basal-like and HER2-enriched
      breast cancer subtypes and the immunoreactive ovarian cancer subtype. Consistent
      with a restricted epitope-driven response, a subset of basal-like and HER2
      enriched breast tumors and immunoreactive ovarian tumors showed high expression
      of a low-diversity population of BCR gene segments. More BCR segments showed
      improved prognosis with increased expression in basal-like breast tumors and
      immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2
      enriched tumors exhibited more BCR sequence variants in regions consistent with
      SHM. CONCLUSION: Taken together, these data suggest the presence of a productive
      and potentially restricted antitumor B-cell response in basal-like breast and
      immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell
      responses may be a promising therapeutic approach to targeting these B-cell
      infiltrated tumors.

PMID- 24916697
TI  - Cisplatin-induced renal injury is independently mediated by OCT2 and p53.
AB  - PURPOSE: Tubular secretion of cisplatin is abolished in mice deficient for the
      organic cation transporters Oct1 and Oct2 (Oct1/2(-/-)mice), and these animals
      are protected from severe cisplatin-induced kidney damage. Since tubular necrosis
      is not completely absent in Oct1/2(-/-)mice, we hypothesized that alternate
      pathways are involved in the observed injury. EXPERIMENTAL DESIGN: Studies were
      done in wild-type, Oct1/2(-/-), or p53-deficient animals, all on an FVB
      background, receiving cisplatin intraperitoneally at 15 mg/kg. Cisplatin
      metabolites were analyzed using mass spectrometry, and gene expression was
      assessed using Affymetrix microarrays and RT-PCR arrays. RESULTS: KEGG pathway
      analyses on kidneys from mice exposed to cisplatin revealed that the most
      significantly altered genes were associated with the p53 signaling network,
      including Cdnk1a and Mdm2, in both wild-type (P = 2.40 * 10(-11)) and Oct1/2(-/
      )mice (P = 1.92 * 10(-8)). This was confirmed by demonstrating that homozygosity
      for a p53-null allele partially reduced renal tubular damage, whereas loss of p53
      in Oct1/2(-/-)mice (p53(-/-)/Oct1/2(-/-)) completely abolished nephrotoxicity. We
      found that pifithrin-alpha, an inhibitor of p53-dependent transcriptional
      activation, inhibits Oct2 and can mimic the lack of nephrotoxicity observed in
      p53(-/-)/Oct1/2(-/-)mice. CONCLUSIONS: These findings indicate that (i) the p53
      pathway plays a crucial role in the kidney in response to cisplatin treatment and
      (ii) clinical exploration of OCT2 inhibitors may not lead to complete
      nephroprotection unless the p53 pathway is simultaneously antagonized.

PMID- 24916700
TI  - TGFalpha and amphiregulin paracrine network promotes resistance to EGFR blockade
      in colorectal cancer cells.
AB  - PURPOSE: Targeted inhibition of EGFR with the mAbs cetuximab or panitumumab is a
      valuable treatment for RAS wild-type colorectal cancers. The efficacy of EGFR
      blockade is limited by the emergence of acquired resistance often attributed to
      secondary KRAS mutations. Remarkably, tumor biopsies from resistant patients show
      that only a fraction of the resilient cells carry KRAS mutations. We hypothesized
      that a paracrine cross-talk driven by the resistant subpopulation may provide in
      trans protection of surrounding sensitive cells. EXPERIMENTAL DESIGN: Conditioned
      medium assays and three-dimensional cocultures were used to assess paracrine
      networks between cetuximab-sensitive and -resistant cells. Production of EGFR
      ligands by cells sensitive to cetuximab and panitumumab was measured. The ability
      of recombinant EGFR ligands to protect sensitive cells from cetuximab was
      assessed. Biochemical activation of the EGFR signaling pathway was measured by
      Western blotting. RESULTS: Colorectal cancer cells sensitive to EGFR blockade can
      successfully grow despite cetuximab treatment when in the company of their
      resistant derivatives. Media conditioned by resistant cells protect sensitive
      parental cells from cetuximab. EGFR blockade triggers increased secretion of
      TGFalpha and amphiregulin. Increased secretion of ligands by resistant cells can
      sustain EGFR/ERK signaling in sensitive cells. CONCLUSIONS: Colorectal cancer
      cells that develop resistance to cetuximab and panitumumab secrete TGFalpha and
      amphiregulin, which protect the surrounding cells from EGFR blockade. This
      paracrine protective mechanism might be therapeutically exploitable.

PMID- 24916699
TI  - Kidney cancer is characterized by aberrant methylation of tissue-specific
      enhancers that are prognostic for overall survival.
AB  - PURPOSE: Even though recent studies have shown that genetic changes at enhancers
      can influence carcinogenesis, most methylomic studies have focused on changes at
      promoters. We used renal cell carcinoma (RCC), an incurable malignancy associated
      with mutations in epigenetic regulators, as a model to study genome-wide patterns
      of DNA methylation at a high resolution. EXPERIMENTAL DESIGN: Analysis of
      cytosine methylation status of 1.3 million CpGs was determined by the HELP assay
      in RCC and healthy microdissected renal tubular controls. RESULTS: We observed
      that the RCC samples were characterized by widespread hypermethylation that
      preferentially affected gene bodies. Aberrant methylation was particularly
      enriched in kidney-specific enhancer regions associated with H3K4Me1 marks.
      Various important underexpressed genes, such as SMAD6, were associated with
      aberrantly methylated, intronic enhancers, and these changes were validated in an
      independent cohort. MOTIF analysis of aberrantly hypermethylated regions revealed
      enrichment for binding sites of AP2a, AHR, HAIRY, ARNT, and HIF1 transcription
      factors, reflecting contributions of dysregulated hypoxia signaling pathways in
      RCC. The functional importance of this aberrant hypermethylation was demonstrated
      by selective sensitivity of RCC cells to low levels of decitabine. Most
      importantly, methylation of enhancers was predictive of adverse prognosis in 405
      cases of RCC in multivariate analysis. In addition, parallel copy-number analysis
      from MspI representations demonstrated novel copy-number variations that were
      validated in an independent cohort of patients. CONCLUSIONS: Our study is the
      first high-resolution methylome analysis of RCC, demonstrates that many kidney
      specific enhancers are targeted by aberrant hypermethylation, and reveals the
      prognostic importance of these epigenetic changes in an independent cohort.

PMID- 24916701
TI  - microRNAome expression in chronic lymphocytic leukemia: comparison with normal B
      cell subsets and correlations with prognostic and clinical parameters.
AB  - PURPOSE: Despite its indolent nature, chronic lymphocytic leukemia (CLL) remains
      an incurable disease. To establish the potential pathogenic role of miRNAs, the
      identification of deregulated miRNAs in CLL is crucial. EXPERIMENTAL DESIGN: We
      analyzed the expression of 723 mature miRNAs in 217 early-stage CLL cases and in
      various different normal B-cell subpopulations from tonsils and peripheral blood.
      RESULTS: Our analyses indicated that CLL cells exhibited a miRNA expression
      pattern that was most similar to the subsets of antigen-experienced and marginal
      zone-like B cells. These normal subpopulations were used as reference to identify
      differentially expressed miRNAs in comparison with CLL. Differences related to
      the expression of 25 miRNAs were found to be independent from IGHV mutation
      status or cytogenetic aberrations. These differences, confirmed in an independent
      validation set, led to a novel comprehensive description of miRNAs potentially
      involved in CLL. We also identified miRNAs whose expression was distinctive of
      cases with mutated versus unmutated IGHV genes or cases with 13q, 11q, and 17p
      deletions and trisomy 12. Finally, analysis of clinical data in relation to miRNA
      expression revealed that miR26a, miR532-3p, miR146-5p, and miR29c* were strongly
      associated with progression-free survival. CONCLUSION: This study provides novel
      information on miRNAs expressed by CLL and normal B-cell subtypes, with
      implication on the cell of origin of CLL. In addition, our findings indicate a
      number of deregulated miRNAs in CLL, which may play a pathogenic role and promote
      disease progression. Collectively, this information can be used for developing
      miRNA-based therapeutic strategies in CLL.

PMID- 24916702
TI  - Phenolcarboxylic acids from medicinal herbs exert anticancer effects through
      disruption of COX-2 activity.
AB  - Integrated research of herbs and formulas characterized by functions of promoting
      blood circulation and removing blood stasis is one of the most active fields in
      traditional Chinese medicine. This paper strives to demonstrate the roles of a
      homologous series of phenolcarboxylic acids from these medicinal herbs in cancer
      treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in
      tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid
      derivatives, cinnamic acid derivatives and their dehydration-condensation
      products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and
      salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549
      cells proliferation. 2D-quantitative method was introduced to describe the
      potential structural features that contributed to certain bioactivities. We also
      found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353
      in COX-2 active site residues. We further extensively focused on danshensu [d-(+)
      beta-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent
      anticancer manner. Both genetic and pharmacological inhibition of COX-2 could
      enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX
      2/PGE2/ERK signaling axis was essential for the anticancer effect of DSS.
      Furthermore, combined treatment with DSS and celecoxib could produce stronger
      anticancer effects in experimental lung metastasis of A549 cells in vivo. All
      these findings indicated that phenolcarboxylic acids might possess anticancer
      effects through jointly targeting COX-2 activity in cancer cells and provided
      strong evidence in cancer prevention and therapy for the herbs characterized by
      blood-activating and stasis-resolving functions in clinic. 

PMID- 24916703
TI  - UPLC-Q/TOF MS standardized Chinese formula Xin-Ke-Shu for the treatment of
      atherosclerosis in a rabbit model.
AB  - Xin-Ke-Shu (XKS), a patent traditional Chinese medicine (TCM) preparation, has
      been commonly used for the treatment of coronary heart disease in China. In order
      to understand its mechanism of action, a metabonomic approach based on ultra
      performance liquid chromatography coupled with quadrupole time-of-flight mass
      spectrometry (UPLC-Q/TOF MS) was utilized to profile the plasma metabolic
      fingerprints of atherosclerosis (AS) rabbits with and without XKS treatment. The
      metabolic profile of model group clearly separated from normal, and that of XKS
      group was closer to the control group. Metabolites with significant changes
      during atherosclerosis were characterized as potential biomarkers related to the
      development of atherosclerosis by using orthogonal partial least-squares
      discriminate analysis (OPLS-DA). Twenty potential biomarkers, including l
      acetylcarnitine (1), propionylcarnitine (2), unknown (3), phytosphingosine (4),
      glycoursodeoxycholic acid (5), LPC(14:0) (6), sphinganine (7), LPC(20:5) (8),
      LPC(16:1) (9), LPC(18:2) (10), LPC(18:3) (11), LPC(22:5) (12), LPC(16:0) (13),
      LPC(18:1) (14), LPC(22:4) (15), LPC(17:0) (16), LPC(20:2) (17), elaidic carnitine
      (18), LPC(18:0) (19) and LPC(20:1) (20), were identified by their accurate mass
      and MS(E) spectra. The derivations of those biomarkers can be regulated by
      administration of XKS, which suggested that the intervention effect of XKS
      against AS may involve in regulating the lipid perturbation including fatty acid
      beta-oxidation pathway, sphingolipid metabolism, glycerophospholipid metabolism
      and bile acid biosynthesis. This study indicated that the UPLC-Q/TOF MS-based
      metabonomics not only gave a systematic view of the pathomechanism of AS, but
      also provided a powerful tool to study the efficacy and mechanism of complex TCM
      prescriptions. 

PMID- 24916704
TI  - Antioxidative effects of Panax notoginseng saponins in brain cells.
AB  - Oxidative stress resulting from accumulation of reactive oxygen species (ROS) is
      involved in cell death associated with neurological disorders such as stroke,
      Alzheimer's disease and traumatic brain injury. Antioxidant compounds that
      improve endogenous antioxidant defenses have been proposed for neural protection.
      The purpose of this study was to investigate the potential protective effects of
      total saponin in leaves of Panax notoginseng (LPNS) on oxidative stress and cell
      death in brain cells in vitro. Lactate dehydrogenase (LDH) assay indicated that
      LPNS (5 MUg/ml) reduced H2O2-induced cell death in primary rat cortical
      astrocytes (23+/-8% reduction in LDH release vs. control). Similar protection was
      found in oxygen and glucose deprivation/reoxygenation induced SH-SY5Y (a human
      neuroblastoma cell line) cell damage (78+/-7% reduction vs. control). The
      protective effects of LPNS in astrocytes were associated with attenuation of
      reactive oxygen species (ROS) accumulation. These effects involved activation of
      Nrf2 (nuclear translocation) and upregulation of downstream antioxidant systems
      including heme oxygenase-1 (HO-1) and glutathione S-transferase pi 1 (GSTP1).
      These results demonstrate for the first time that LPNS has antioxidative effects
      which may be neuroprotective in neurological disorders.

PMID- 24916705
TI  - Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia
      miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient
      mice.
AB  - Aortic aneurysm (AA) is a life-threatening vascular disease in defect of
      effective pharmaceutical therapy. Matrix metalloproteinase-9 (MMP-9) is
      implicated in the development of chronic vascular diseases including aneurysm,
      but the effective MMP-9 inhibitors are far from development. To develop new
      candidate for AA therapy, we evaluated the efficiency of salvianolic acid A
      (SalA), a novel MMP-9 inhibitor, on AA progression in a mouse model and
      characterized the mechanism of action. SalA is a water soluble compound of the
      herbal drug Rhizoma Salviae miltiorrhizae (Danshen) which in China is widely used
      for the treatment of hypertension, coronary artery diseases and myocardial
      infarction. MMPs activity was evaluated by enzyme kinetic analysis in vitro and
      in-gel gelatin zymography in vivo. SalA showed selectivity on gelatinase (MMP-2
      and MMP-9) than on collagenase (MMP-8 and MMP-13) in vitro, and specificity on
      MMP-9 than MMP-2 in vivo. Aortic aneurysm was induced by angiotension II (AngII)
      in apolipoprotein E-deficient (ApoE(-/-)) mice. Aortic structure was evaluated by
      hematoxylin and eosin, picrosirius red, orein stain. Macrophage infiltration was
      detected by immunohistochemistry in vivo and transwell in vitro. Comparing with
      doxycycline (Dox), a well-known MMPs inhibitor, SalA showed similar efficiency
      against AA progression. SalA significantly decreased aortic diameter and aneurysm
      severity, ameliorated integrity of vascular structure, inhibited elastin
      fragmentation and macrophage infiltration. Furthermore, SalA showed greater
      safety than Dox based on hepatotoxicity evaluation. Our results demonstrated that
      SalA held great potential for AA therapy. 

PMID- 24916706
TI  - Activity of cycloartane-type triterpenes and sterols isolated from Musa
      paradisiaca fruit peel against Leishmania infantum chagasi.
AB  - The aim of the study was to evaluate in vitro the antileishmanial activity of
      triterpenes and sterols isolated from Musa paradisiaca (banana) fruit peel used
      traditionally to treat leishmaniasis. The compounds were isolated from the
      ethanolic extract of the peel of the banana fruit by column chromatography. The
      chemical structure of compounds was determined by (1)H and (13)C - nuclear
      magnetic resonance spectroscopy. The cytotoxicity was measured in RAW 264.7 cells
      and LLC-MK2. Leishmanicidal activity against L. infantum chagasi promastigotes
      was performed by the MTT colorimetric method and activity against amastigotes was
      assayed in mammalian cells using in situ ELISA method. Five compounds were
      identified, consisting of three triterpenes: cycloeucalenone, 31
      norcyclolaudenone and 24-methylene-cicloartanol and a mixture of two sterols:
      beta-sitosterol and stigmasterol. With the exception of cycloeucalenone, all
      compounds showed statistically similar activity against promastigote to
      pentamidine. While, acting against amastigotes, excluding 31-norcyclolaudenone,
      other compounds showed activity similar to amphotericin B. All compounds showed
      low cytotoxicity in mammalian cells. CONCLUSION: This study partially confirms
      the use of Musa paradisiaca in folk medicine against leishmaniasis. Further in
      vivo studies are necessary to evaluate the efficacy.

PMID- 24916707
TI  - Tolerance and effect of an add-on treatment with a cough medicine containing ivy
      leaves dry extract on lung function in children with bronchial asthma.
AB  - Ivy leaves dry extract is registered as an expectorant in patients with
      respiratory diseases associated with productive cough. Next to its secretolytical
      properties, bronchospasmolytical effects are described. However only limited data
      exist about a possible therapeutical effect in asthmatic patients. In this double
      blind, placebo-controlled, randomized cross-over study, 30 children (median age
      9.07 years (min-max: 6-11)) suffering from partial or uncontrolled mild
      persistent allergic asthma despite long-term treatment with 400 MUg budesonide
      equivalent were investigated. After a four week run-in period, patients either
      received ivy leaves dry extract for four weeks in addition to their inhaled
      corticosteroid therapy or placebo, followed by a wash-out phase before switching
      to the other treatment arm. Lung function, FeNO, exhaled breath condensate pH and
      life quality was analyzed after each treatment period. There was a significant
      improvement of MEF(75-25), MEF25 and VC after treatment with ivy leaves dry
      extract (MEF(75-25) change in the mean 0.115 l/s, p=0.044; MEF25 change in the
      mean 0.086 l/s, p=0.041; VC change in the mean 0.052 l, p=0.044), but not after
      treatment with placebo. For the primary outcome parameters (relative change of
      FEV1 and MEF(75-25) before bronchodilation) no treatment effect could be detected
      in the cross-over analysis (FEV1 p=0.6763 and MEF(75-25) p=0.6953). This proof-of
      concept study indicates that children with mild uncontrolled asthma despite
      regular inhaled corticosteroid therapy might benefit from an additional therapy
      with ivy leaves dry extract. However, further studies are needed.

PMID- 24916708
TI  - Inhibitory effect of paeoniflorin on methylglyoxal-mediated oxidative stress in
      osteoblastic MC3T3-E1 cells.
AB  - PURPOSE: Methylglyoxal (MG) has been suggested to be one major source of
      intracellular reactive carbonyl compounds. In the present study, the effect of
      paeoniflorin on MG-induced cytotoxicity was investigated using osteoblastic MC3T3
      E1 cells. METHODS: Osteoblastic MC3T3-E1 cells were pre-incubated with
      paeoniflorin before treatment with MG, and markers of oxidative damage and
      mitochondrial function were examined. RESULTS: Pretreatment of MC3T3-E1 cells
      with paeoniflorin prevented the MG-induced cell death and formation of
      intracellular reactive oxygen species, cardiolipin peroxidation, and protein
      adduct in osteoblastic MC3T3-E1 cells. In addition, paeoniflorin increased
      glutathione level and restored the activity of glyoxalase I to almost the control
      level. These findings suggest that paeoniflorin provide a protective action
      against MG-induced cell damage by reducing oxidative stress and by increasing MG
      detoxification system. Pretreatment with paeoniflorin prior to MG exposure
      reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane
      potential dissipation and adenosine triphosphate loss. Additionally, the nitric
      oxide and nuclear respiratory factor 1 levels were significantly increased by
      paeoniflorin, suggesting that paeoniflorin may induce mitochondrial biogenesis.
      Paeoniflorin treatment decreased the levels of proinflammatory cytokines such as
      TNF-alpha and IL-6. CONCLUSIONS: These findings indicate that paeoniflorin might
      exert its therapeutic effects via upregulation of glyoxalase system and
      mitochondrial function. Taken together, paeoniflorin may prove to be an effective
      treatment for diabeteic osteopathy.

PMID- 24916709
TI  - New ways of defining protein and energy relationships in inborn errors of
      metabolism.
AB  - Dietary restrictions required to manage individuals with inborn errors of
      metabolism (IEM) are essential for metabolic control, however may result in an
      increased risk to both short and long-term nutritional status. Dietary factors
      most likely to influence nutritional status include energy intake, protein
      quality and quantity, micronutrient intake and the frequency and extent to which
      the diet must be altered during periods of increased physical or metabolic
      stress. Patients on the most restrictive diets, including those with intakes
      consisting of low levels of natural protein or those with recurrent illness or
      frequent metabolic decompensation carry the most nutritional risk. Due to the
      difficulties in determining condition specific requirements, dietary intake
      recommendations and nutritional monitoring tools used in patients with IEM are
      the same as, or extrapolated from, those used in healthy populations. As a
      consequence, evidence is lacking for the safest dietary prescriptions required to
      manage these patients long term, as tolerance to dietary therapy is generally
      described in terms of metabolic stability rather than long term nutritional and
      health outcomes. As the most frequent therapeutic dietary manipulation in IEM is
      alteration in dietary protein, and as protein status is critically dependent on
      adequate energy provision, the use of a Protein to Energy ratio (P:E ratio) as an
      additional tool will better define the relationship between these critical
      components. This could accurately define dietary quality and ensure that not only
      an adequate, but also a safe and balanced intake is provided. 

PMID- 24916710
TI  - Letter to the editor: symptomatic pulmonary embolus after joint arthroplasty:
      stratification of risk factors.

PMID- 24916711
TI  - Reply to the letter to the editor: symptomatic pulmonary embolus after joint
      arthroplasty: stratification of risk factors.

PMID- 24916712
TI  - Isolation and reversible dimerization of a selenium-selenium three-electron sigma
      bond.
AB  - Three-electron sigma-bonding that was proposed by Linus Pauling in 1931 has been
      recognized as important in intermediates encountered in many areas. A number of
      three-electron bonding systems have been spectroscopically investigated in the
      gas phase, solution and solid matrix. However, X-ray diffraction studies have
      only been possible on simple noble gas dimer Xe?Xe and cyclic framework
      constrained N?N radical cations. Here, we show that a diselena species modified
      with a naphthalene scaffold can undergo one-electron oxidation using a large and
      weakly coordinating anion, to afford a room-temperature-stable radical cation
      containing a Se?Se three-electron sigma-bond. When a small anion is used, a
      reversible dimerization with phase and marked colour changes is observed: radical
      cation in solution (blue) but diamagnetic dimer in the solid state (brown). These
      findings suggest that more examples of three-electron sigma-bonds may be
      stabilized and isolated by using naphthalene scaffolds together with large and
      weakly coordinating anions. 

PMID- 24916713
TI  - Experience with OxyELITE pro and acute liver injury in active duty service
      members.
AB  - 1,3-dimethylamylamine (DMAA) is a common additive in sport supplements that was
      banned by the FDA in 2013. Specifically, this additive received much publication
      for its role in causing adverse cardiovascular events, particularly sudden
      cardiac death. However, it has been our experience that products containing this
      additive may also lead to acute liver injury and liver failure. We present a
      series of seven cases encountered by a military treatment facility in Southern
      California which involved the use of OxyELITE Pro, a sport supplement containing
      DMAA, that all resulted in acute liver injury with two cases requiring transplant
      for acute liver failure. To our knowledge, this is the first case series reported
      involving OxyELITE Pro or other DMAA-containing supplements with a specific focus
      on acute liver injury. This review is limited by the paucity of clinical studies
      and trials based on OxyElite Pro and its effect on the liver. The presented cases
      are notably observation, and no standardized diagnostic or treatment protocol was
      utilized. This series is important to the general population as a whole due to
      the prevalence of sport supplement use, and is particularly important for
      practitioners who work with the military or athletic populations due to the high
      use in these demographics. These cases are followed by a brief discussion
      regarding DMAA. 

PMID- 24916714
TI  - Metabolic kinetics of 5-hydroxytryptamine and the research targets of functional
      gastrointestinal disorders.
AB  - 5-Hydroxytryptamine (5-HT) is an important neurotransmitter in both the central
      and enteric nervous systems. It has diverse functions in regulating
      gastrointestinal motility and visceral sensitivity, emotion, appetite, pain and
      sensory perception, cognition, sexual activity and sleep. These functions are
      mainly associated with the metabolic kinetics of 5-HT in different tissues.
      Tryptophan hydroxylase is the rate-limiting enzyme and modulates serotonin
      synthesis. Vesicular monoamine transporter 1 plays a role in 5-HT storage and
      release. Degradation of 5-HT is mediated by monoamine oxidase-A. All these
      factors influence the action of 5-HT in vivo. Functional gastrointestinal
      disorders (FGIDs) are characterized by a series of symptoms including abdominal
      pain, diarrhea, constipation, anxiety and depression, in the absence of
      identifiable structural or biochemical abnormalities. They are frequently
      accompanied by changed gut motility or visceral sensitivity. An increasing body
      of research has found FGIDs to be closely associated with 5-HT, and drugs such as
      citalopram, paroxetine, venlafaxine, alosetron, tegaserod, prucalopride and
      mosapride have all been developed or discovered from the perspective of the
      metabolic kinetics of 5-HT. This review discusses the relationship between the
      metabolic kinetics of 5-HT and research targets in the field of FGIDs and
      suggests areas of future study that may be useful for understanding these
      disorders and identification of potential therapeutic targets. 

PMID- 24916715
TI  - Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.
AB  - Present research deals with the development of compression-coated flurbiprofen
      colon-targeted tablets to retard the drug release in the upper gastro intestinal
      system, but progressively release the drug in the colon. Flurbiprofen core
      tablets were prepared by direct compression method and were compression coated
      using sodium alginate and Eudragit S100. The formulation is optimized based on
      the in vitro drug release study and further evaluated by X-ray imaging and
      pharmacokinetic studies in healthy humans for colonic delivery. The optimized
      formulation showed negligible drug release (4.33 +/- 0.06 %) in the initial lag
      period followed by progressive release (100.78 +/- 0.64 %) for 24 h. The X-ray
      imaging in human volunteers showed that the tablets reached the colon without
      disintegrating in the upper gastrointestinal tract. The C max of colon-targeted
      tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release
      tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of
      compression-coated tablets to target the colon. Development of compression-coated
      tablets using combination of time-dependent and pH-sensitive approaches was
      suitable to target the flurbiprofen to colon. 

PMID- 24916716
TI  - The associations between psychosocial working conditions and changes in common
      mental disorders: a follow-up study.
AB  - BACKGROUND: Common mental disorders (CMD) are prevalent in working populations
      and have adverse consequences for employee well-being and work ability, even
      leading to early retirement. Several studies report associations between
      psychosocial working conditions and CMD. However, there is a lack of longitudinal
      research within a broad framework of psychosocial working conditions and
      improvement in CMD. The aim of this study was to examine the associations between
      several psychosocial working conditions and deteriorating and improving CMD among
      ageing employees over a five-to-six-year follow-up period. METHODS: The study is
      based on the Helsinki Health Study baseline survey in 2001-2002 and a follow-up
      in 2007 (N = 4340, response rate 83%) conducted among 40-60-year-old female and
      male employees. The General Health Questionnaire (GHQ-12) was used to measure
      common mental disorders. Psychosocial working conditions were measured in terms
      of job strain, organisational justice, work-family interface, social support and
      workplace bullying. The covariates included sociodemographic and health factors.
      RESULTS: Following adjustment for all the covariates, family-to-work (OR 1.41,
      95% Cl 1.04-1.91) and work-to-family conflicts (OR 1.99, 95% Cl 1.42-2.78) and
      workplace bullying (OR 1.40, 95% Cl 1.09-1.79) were associated with
      deterioration, and family-to-work conflicts (OR 1.65, 95% Cl 1.66-2.34) and
      social support (OR 1.47, 95% Cl 1.07-2.00) with improvement in CMD. CONCLUSIONS:
      Adverse psychosocial working conditions contribute to poor mental health among
      employees. Preventing workplace bullying, promoting social support and achieving
      a better balance between work and family may help employees to maintain their
      mental health.

PMID- 24916717
TI  - Semi-imprinting quercetin into poly[N,N-dimethylacrylamide-co-3, 9-divinyl-2, 4,
      8, 10-tetraoxaspiro (5.5) undecane] network: evaluation of the antioxidant
      character.
AB  - A responsive antioxidant system constituted from quercetin inserted into poly[N,N
      dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane]
      through a semi-imprinted procedure was evaluated. A continuous magnetic field
      (MF) was used during supramolecular structure preparation. The strength of
      coupling quercetin was evaluated based on the template release from the polymeric
      matrices, as well as to what extent quercetin reloaded into the polymer matrix in
      prescribed conditions--with or without the MF presence--shows antioxidant
      properties. The antioxidant activity of the complex was investigated by radical
      inhibitor activity method using 2, 2-diphenyl-l-picrylhydrazyl. The evaluation of
      the homogeneity distribution of the quercetin inside the polymeric network was
      made by near-infrared chemical imaging and correspondingly statistical analysis.
      For in vivo biocompatibility investigation, granuloma test in rats was performed
      correlated with the activity of enzymes involved in oxidative stress as well as
      immunologic effects of tested supramolecular complexes that include quercetin as
      therapeutic agent.

PMID- 24916718
TI  - In vitro isolation and cultivation of human chondrocytes for osteoarthritis
      renovation.
AB  - The purpose of this study was to evaluate the repair effects of chondrocytes that
      were cultured in vitro on osteoarthritis (OA). Chondrocytes were isolated from
      fetal rabbits and cultured in Biosilon microcarriers. Sixty rabbits were randomly
      divided into three groups equally (blank group, model group, treatment group).
      The rabbit knee OA model was established by inducing papain. Rabbits in the
      treatment group were injected with the chondrocytes that were cultured in vitro.
      Hematoxylin-eosin (HE) staining and gross morphologic observation were conducted.
      Expression level of cytokines such as IL-1bbeta, IL-6, and TNF-alpha in cartilage
      synovial cells was also analyzed by an ELISA assay. The cultured chondrocyte was
      validated by a positive stain of type II collagen and vimentin by
      immunofluorescence. Compared to the model group, the articular cartilage of the
      rabbit knee in the treatment group showed a normal color, smooth surface, and
      none of malacia and coloboma. HE staining indicated that the articular surface of
      the treatment group tended to be smooth and flat; the matrix stained tinge and
      the cartilage destruction and fiber hyperplasia of the synovia were lightened.
      The expression levels of IL-1bbeta, IL-6, and TNF-alpha also declined in the
      treatment group. OA symptoms were improved by treating with chondrocytes. In
      summary, the animal experiment in the present study indicated that chondrocyte
      injection played an active effect on renovation of OA. 

PMID- 24916719
TI  - Dietary protein sources in early adulthood and breast cancer incidence:
      prospective cohort study.
AB  - OBJECTIVE: To investigate the association between dietary protein sources in
      early adulthood and risk of breast cancer. DESIGN: Prospective cohort study.
      SETTING: Health professionals in the United States. PARTICIPANTS: 88,803
      premenopausal women from the Nurses' Health Study II who completed a
      questionnaire on diet in 1991. MAIN OUTCOME MEASURE: Incident cases of invasive
      breast carcinoma, identified through self report and confirmed by pathology
      report. RESULTS: We documented 2830 cases of breast cancer during 20 years of
      follow-up. Higher intake of total red meat was associated with an increased risk
      of breast cancer overall (relative risk 1.22, 95% confidence interval 1.06 to
      1.40; P(trend) = 0.01, for highest fifth v lowest fifth of intake). However,
      higher intakes of poultry, fish, eggs, legumes, and nuts were not related to
      breast cancer overall. When the association was evaluated by menopausal status,
      higher intake of poultry was associated with a lower risk of breast cancer in
      postmenopausal women (0.73, 0.58 to 0.91; P(trend) =0.02, for highest fifth v
      lowest fifth of intake) but not in premenopausal women (0.93, 0.78 to 1.11;
      P(trend) = 0.60, for highest fifth v lowest fifth of intake). In estimating the
      effects of exchanging different protein sources, substituting one serving/day of
      legumes for one serving/day of red meat was associated with a 15% lower risk of
      breast cancer among all women (0.85, 0.73 to 0.98) and a 19% lower risk among
      premenopausal women (0.81, 0.66 to 0.99). Also, substituting one serving/day of
      poultry for one serving/day of red meat was associated with a 17% lower risk of
      breast cancer overall (0.83, 0.72 to 0.96) and a 24% lower risk of postmenopausal
      breast cancer (0.76, 0.59 to 0.99). Furthermore, substituting one serving/day of
      combined legumes, nuts, poultry, and fish for one serving/day of red meat was
      associated with a 14% lower risk of breast cancer overall (0.86, 0.78 to 0.94)
      and premenopausal breast cancer (0.86, 0.76 to 0.98). CONCLUSION: Higher red meat
      intake in early adulthood may be a risk factor for breast cancer, and replacing
      red meat with a combination of legumes, poultry, nuts and fish may reduce the
      risk of breast cancer.

PMID- 24916720
TI  - Evaluation of two-step haemoglobin screening with HemoCue for blood donor
      qualification in mobile collection sites.
AB  - BACKGROUND AND OBJECTIVES: Inaccuracy of fingerstick haemoglobin compromises
      donor's health and losses blood donations. We evaluated the benefit of double
      haemoglobin screening with HemoCue. STUDY DESIGN AND METHODS: Blood donors
      underwent fingerstick screening by HemoCue and were driven for donation if
      capillary haemoglobin was within the regulatory range. Those failing were drawn
      venous blood and donated if their venous haemoglobin determined with HemoCue was
      acceptable. RESULTS: Of 276 605 donor clinic visits, 10 011 (3.6%) were assessed
      by two-step haemoglobin screening using HemoCue, because of low (n = 9444) or
      high (n = 567) capillary haemoglobin. Among these, 2561 (25.6%) were deemed
      eligible [recovered donations]. The recovery rate was 23.8% and 55.0% among
      donors presenting with low and high capillary haemoglobin, respectively. In both
      categories of attempted donations, capillary and venous haemoglobin with HemoCue
      correlated significantly in recovered donors (R(2)  ~ 0.5-0.7) but not in
      deferred visits (R(2)  < 0.15). Venous haemoglobin with HemoCue and by
      haematological analyzer significantly correlated in all donations attempts (R(2) 
      ~ 0.7). Donors presenting with low capillary haemoglobin showed small bias
      between capillary and venous haemoglobin by HemoCue (-2.4 +/- 6.2 g/l),
      fingerstick haemoglobin and venous haemoglobin with counter (1.3 +/- 7.3 g/l),
      and venous haemoglobin with HemoCue and counter (3.7 +/- 3.9 g/l). This bias was
      slightly greater in donors with high capillary haemoglobin (-7.5 +/- 7.8, 13.7 +/
      7.5, and 6.2 +/- 7.5, respectively). Double haemoglobin screening by HemoCue
      reached an accuracy of 87.3% for qualifying donors presenting with low
      fingerstick haemoglobin. CONCLUSIONS: Double haemoglobin measurement with HemoCue
      [fingerstick and venous blood if required] is feasible and allows a significant
      recovery of blood donations.

PMID- 24916721
TI  - Multilocus sequence analysis of 'Candidatus Phytoplasma asteris' strain and the
      genome analysis of Turnip mosaic virus co-infecting oilseed rape.
AB  - AIM: Molecular characterization of a pathogenic complex infecting winter oilseed
      rape (Brassica napus ssp. oleifera (DC.) Metzg.) plants showing typical rape
      phyllody symptoms along with some atypical changes. METHODS AND RESULTS:
      Phytoplasma ('Candidatus Phytoplasma') presence was confirmed by PCR-RFLP and 16S
      rRNA gene sequencing. Phylogenetic analyses of phytoplasma amp, tufB, secY, groEL
      and ribosomal protein genes confirmed its affiliation to the 'Ca. P. asteris'
      species. However, in the amp gene encoding a specific protein crucial for insect
      transmission specificity, significant SNPs were found. Biological and serological
      tests revealed the co-infection with Turnip mosaic virus (TuMV). The phylogenetic
      analysis of full TuMV genome sequence, the first reported from the Balkans,
      classified it into the world-B phylogenetic lineage. CONCLUSIONS: A pathogenic
      complex consisting of 'Ca. P. asteris' and TuMV found to co-infect oilseed rape
      plants for the first time was molecularly characterized. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Rape phyllody is a serious problem in rapeseed production. The
      molecular information from this first multi-gene analysis of 'Ca. P. asteris'
      strain associated with rape phyllody as well as the first report of the complete
      sequence of TuMV isolate from the Balkans is a starting point for understanding
      the disease complexity and management.

PMID- 24916723
TI  - Separating xylene isomers by commensurate stacking of p-xylene within channels of
      MAF-X8.
AB  - The development of energy-efficient processes for selective separation of p
      xylene from mixtures with its isomers is of vital importance in the petrochemical
      industries. Current industrial practice uses BaX zeolite that has high adsorption
      selectivity for p-xylene. Finding para-selective structures is challenging. With
      state-of-the-art simulation methodologies we systematically screened a wide
      variety of zeolites and metal-organic frameworks (MOFs). Our investigations
      highlight the crucial importance of the channel dimension on the separation. MAF
      X8 is particularly noteworthy because the channel dimensions and geometry allow
      "commensurate stacking" which we exploit as a separation mechanism at saturation
      conditions. Due to a significantly improved capacity compared to BaX, the cycle
      times for p-xylene with MAF-X8 are found to be about a factor of 4.5 longer. This
      is expected to result in significant process improvements. 

PMID- 24916722
TI  - Individual Differences in the Psychobiological Response to Psychosocial Stress
      (Trier Social Stress Test): The Relevance of Trait Anxiety and Coping Styles.
AB  - The main objective of this study was to investigate the contribution of some
      personality traits to the physiological and psychological response to a
      standardized laboratory psychosocial stressor (trier social stress test).
      Cortisol and affective response (anxiety and mood) were analysed in a mixed-sex
      group composed of 35 young adults who participated in a crossover design (18 men
      and 17 women). After verifying a statistically significant response to the trier
      social stress test in all parameters studied in both sex groups, exploratory
      cluster analyses were carried out to identify sub-groups based on their
      psychophysiological responses. These analyses showed two different groups:
      subjects displaying lower psychological response along with higher cortisol
      response (cluster 1) compared with the group with high affective reactivity along
      with lower cortisol response (cluster 2). Interestingly, we also found
      significant differences in trait anxiety and coping styles when the two clusters
      were compared. Subjects in cluster 1 showed lower scores on trait anxiety and
      higher scores on active coping, whereas the subjects in the second cluster
      obtained higher scores on anxiety and on coping focused on emotions and mental
      disengagement. These findings support the importance of personality traits and
      coping styles in understanding the overall integrative psychobiological
      responsiveness to social stress.

PMID- 24916724
TI  - Interventions to improve adolescents' contraceptive behaviors in low- and middle
      income countries: a review of the evidence base.
AB  - OBJECTIVE(S): Many adolescents in developing countries have an unmet need for
      contraception, which can contribute to poor reproductive health outcomes. Recent
      literature reviews have not adequately captured effective contraceptive services
      and interventions for adolescents in low- and middle-income countries (LMICs).
      This study aims to identify and evaluate the existing evidence base on
      contraceptive services and interventions for adolescents in LMICs that report an
      impact on contraceptive behavior outcomes. STUDY DESIGN: Structured literature
      review of published and unpublished papers about contraceptive services and
      interventions for adolescents in LMICs that report an impact on contraceptive
      behavior outcomes. RESULTS: We identify common elements used by programs that
      measured an impact on adolescent contraceptive behaviors and summarize outcomes
      from 15 studies that met inclusion criteria. Effective programs generally
      combined numerous program approaches and addressed both user and service
      provision issues. Overall, few rigorous studies have been conducted in LMICs that
      measure contraceptive behaviors. Few interventions reach the young, the out of
      school and other vulnerable groups of adolescents. CONCLUSION(S): Though the
      evidence base is weak, there are promising foundations for adolescent
      contraceptive interventions in nearly every region of the world. We offer
      recommendations for programmers and identify gaps in the evidence base to guide
      future research.

PMID- 24916725
TI  - The shame of existing: an extreme form of shame.
AB  - This paper presents 'the shame of existing' as a form of shame that is deeper and
      more extensive than those customarily encountered. 'The shame of existing' is
      defined as shame about existing as we are and especially at the fact that we are.
      It is accompanied by merciless and total rejection of the subject's self and by
      feelings of extreme worthlessness and inferiority coupled with the all-pervasive
      conviction that it would be better not to exist. On the basis of clinical
      material, consideration is given to the specific transference and
      countertransference aspects of analyses in which the shame of existing
      constitutes an important part of the patient's pathology. Disturbance of handling
      and holding by the primary objects right from birth is suggested as the earliest
      developmental basis of the shame of existing. This disturbance is attributed to
      hate and rejection of the infant by the primary objects and to the infant's not
      being touched emotionally and physically and not having its right to exist
      acknowledged. The paper begins with an introduction to shame as an affect and as
      a concept in psychoanalytic theory.

PMID- 24916726
TI  - Editorial.

PMID- 24916727
TI  - Predictors of anxiety symptoms in the gynecological outpatient setting: The Thai
      experience.
AB  - Objective. To examine the prevalence and predictors of anxiety in women attending
      a gynecological outpatient service. Method. A total of 271 women who came to a
      gynecological outpatient clinic at a large university hospital in Bangkok,
      Thailand, were asked to complete the state sub-scale of the Spielberger State
      Trait Anxiety Index (STAI) and a questionnaire to obtain demographic, medical and
      gynecological information as well as a questionnaire to assess social support. A
      cutoff score of >= 46 on the STAI was considered to indicate the presence of
      moderate-severe anxiety. Result. One hundred (36.9%) subjects met criteria for
      anxiety. Anxious women were more likely to be young and to have had an abortion
      at an earlier age. They were more likely to reside in rural Thailand, report
      perception of low social support, present with abnormal vaginal discharge and to
      have a greater number of gynecological symptoms than non-anxious women.
      Additionally, anxious women were less likely to have knowledge about their
      diagnosis compared to non-anxious women. Conclusion. Clinically meaningful levels
      of anxiety are common among women attending an outpatient gynecological clinic.
      Awareness of risk factors for anxiety in these women will aid medical personnel
      in identifying those in need of additional support and/or mental health services.

PMID- 24916728
TI  - Switching to duloxetine from selective serotonin reuptake inhibitors in non- or
      partial responders: Results from a Spanish sample.
AB  - Objectives. To evaluate the efficacy and safety of switching from a selective
      serotonin reuptake inhibitor (SSRI) to duloxetine in non- or partial responders.
      Methods. This is a post-hoc analysis of the pooled data of the Spanish sample
      from an open-label, multicentre study. Additionally, a 6-month continuation
      safety phase was performed. Results. A total of 156 patients were switched to
      duloxetine from SSRIs. More than 83% completed the acute phase, of whom 75% went
      into the continuation phase. At baseline, the mean duration of SSRI treatment was
      71.2 weeks and the HAM-D17 mean score was 22.4. In the acute-phase, symptoms
      severity significantly improved after 10 weeks of duloxetine treatment as
      measured by mean change from baseline in HAM-D17 total score (-10.5; P<0.001) and
      all secondary efficacy measures, including painful symptoms. Response (>=50%
      decrease in HAM-D17 total score) and remission rates (HAM-D17 total score <= 7)
      were 52.9 and 27.7%, respectively. The most common adverse events reported in
      both phases were headache (11.5% [acute]; 6.1% [continuation]) and nausea (6.4%
      [acute]; 5.1% [continuation]). Conclusions. In a population of Spanish SSRI non-
      and partial responders, switch to duloxetine was associated with significant
      improvement in emotional and painful symptoms of depression. Duloxetine was well
      tolerated and safe during both phases. 

PMID- 24916729
TI  - Treating depression with different galenical drug formulations: Does it make a
      difference? The comparison of mirtazapine fast dissolving formulation (FDT) with
      conventional mirtazapine tablets (CT).
AB  - Objective. To assess clinical advantages of fast dissolving tablet (FDT)
      formulation of mirtazapine by comparison to conventional (CT) mirtazapine tablets
      in the treatment of depressed patients. Methods. A posteriori analyses of pooled
      data of a total of 30 studies (of at least 6 weeks duration, total N=3510) with
      CT and FDT in depressed patients was performed. Weight changes were recorded at
      baseline and regular intervals until the end of the study. Patient preferences
      for the one or the other formulation, as well as the appraisal of the FDT
      qualities, were assessed by means of a global internet-based survey including
      5,428 patients. Results. Compared with mirtazapine CT, the FDT was associated
      with an average 0.3 kg less weight increase (P=0.0015) during the 6 weeks of
      treatment. The qualities and preference for FDT (global survey) were positively
      evaluated by the majority of patients. Particular advantages of FDT over CT were:
      better compliance (47.3% of raters), taste, ease and overall convenience of use
      (>75% of raters). Conclusions. The FDT mirtazapine differed from conventional
      tablets (CT) not only regarding somewhat less weight increase and overall use
      preference, but more importantly, regarding better compliance with treatment. 

PMID- 24916730
TI  - Screening for bipolar disorder in medicated patients treated for unipolar
      depression in a psychiatric outpatient clinic using the Mood Disorder
      Questionnaire.
AB  - Objective. The aim of this study was to examine the rate of the misdiagnosis of
      bipolar disorder in outpatients who had been treated for unipolar depression with
      antidepressants in Taiwan and to verify the validity of the Mood Disorder
      Questionnaire (MDQ) in this population. Method. Fifty-three outpatients who had
      been treated for unipolar depression were recruited. All patients completed the
      MDQ and were administered the Structured Clinical Interview. The sensitivity and
      specificity were calculated for each possible MDQ symptom cut-off score relative
      to a Structured Clinical Interview diagnosis of bipolar spectrum disorder.
      Results. A total of 11.3% were diagnosed with bipolar spectrum disorder. The
      optimal model we found contained only the first portion of the MDQ with a cut-off
      score of 2. This model provided both good sensitivity (0.83) and specificity
      (0.53). Conclusion. The misdiagnosis of bipolar disorder as unipolar depression
      disorder is prevalent. Based on the results of the current study, the probability
      of bipolar disorder in depression outpatients who are in a mildly depressed state
      and score higher than 2 points in the first portion of the MDQ deserves to be
      investigated. 

PMID- 24916731
TI  - Algorithm-driven treatment for bipolar disorder in Korea: Clinical feasibility,
      efficacy, and safety.
AB  - Objective. The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP
      2002) was developed in 2002. The aim of this study was to evaluate the clinical
      feasibility, efficacy, and safety of implementation of the KMAP-BP 2002 algorithm
      in clinical situations. Methods. Participating investigators were asked to follow
      the KMAP-BP 2002 algorithm as much as possible, but they were allowed to change
      their treatment strategies as they considered necessary. The enrolled patients
      were followed for 4 months. Results. A total of 126 bipolar patients were
      consecutively enrolled and 73% were treated according to the KAMP-BP 2002
      algorithm. The majority (79%) of manic patients demonstrated a treatment response
      at the starting step and were thus treated with only one step of the algorithm.
      An atypical antipsychotic drug was coadministered with a mood stabilizer from the
      beginning of treatment in almost all manic patients. There was a significant
      improvement in manic symptoms (F=187.32, P<0.001) over the 4-month testing
      period. There was no significant increase in side effects at the endpoint.
      Overall, the investigators were satisfied with implementing the algorithm.
      Conclusion. These results suggest that the KMAP-BP 2002 algorithm could be
      implemented effectively and safely in clinical practice. 

PMID- 24916732
TI  - Treatment response and duration of maintenance treatment with adjunctive
      antidepressants in bipolar depression: A retrospective chart review.
AB  - Objective. The aim of this study was to investigate the treatment response and
      optimal maintenance period of antidepressants to minimize the risk of switching
      in bipolar depression in clinical practice. Methods. In a retrospective chart
      review, 78 bipolar patients, treated for a depressive episode by adding
      antidepressant to ongoing mood-stabilizing medications and had been followed for
      at least 6 months were identified. We determined recovery to euthymia and/or
      switching into mania during the 6-month follow-up period and estimated the time
      from antidepressant initiation to mood change. Results. Antidepressants treatment
      responses were classified into four groups. In one group, depression was
      sustained for 6 months despite continuous antidepressant treatment (poor-response
      group, 10.3%). In the second, abrupt switch into mania occurred during
      antidepressant treatment (acute-switch group, 19.2%). In the third, the
      depression improved to euthymia without manic switching (good-response group,
      50%). In the fourth, the depression improved to euthymia but manic switching
      occurred during maintenance with antidepressants (delayed-switch group, 20.5%),
      and the mean duration of antidepressants maintenance was 54.6+/-38.9 days.
      Conclusions. Bipolar depression has heterogeneous treatment responses to
      adjunctive antidepressant. Antidepressants should be discontinued within 8 weeks
      after improvement to euthymia to minimize the risk of manic switching. 

PMID- 24916733
TI  - A descriptive, open-label, long-term follow-up survey of psychotic patients
      receiving risperidone long-acting injectable: Preliminary results.
AB  - Objective. To assess clinical development in patients with psychotic disorders
      who received risperidone long-acting injectable (RLAI) in combination with
      psychosocial interventions as part of daily clinical practice in France. Methods.
      In this 18-month survey, patients were started on bi-monthly RLAI injections and
      integrated in a psychosocial treatment programme. Clinical progression was
      evaluated using the Clinical Global Impression of Severity (CGI-S) and Global
      Assessment of Functioning (GAF) scales. In addition, data on patient
      characteristics, adherence, RLAI dosage, concomitant medications and rates and
      durations of hospitalization were collected. Results. Of the total of 120
      patients included in the survey, 95 (79.2%) had previously received other
      treatments. Non-adherence was the most frequently reported reason for changing to
      RLAI (93 patients, 97.9%). With RLAI treatment, mean CGI-S scores improved from
      5.6+/-0.5 at baseline to 3.6+/-1.1 at 18 months, whilst mean GAF scores increased
      from 34.0+/-12.7 to 67+/-13.5 (both P<0.0001). Furthermore, patients had fewer
      and shorter hospitalizations during the 18 months of RLAI treatment, compared to
      the preceding 18 months. Conclusions. Patients with psychotic disorders benefited
      from RLAI treatment in combination with psychosocial interventions, as shown by
      improvements in their clinical status and functioning and reduced hospitalization
      rates. 

PMID- 24916734
TI  - Schizophrenic patients have a preference for symmetrical rectangles: A comparison
      with preferences of university students.
AB  - Objective. We examined figure preferences of 26 schizophrenic patients and a
      control group of 53 controls (university students). Methods. Figures utilized
      included a square and six different rectangles of equal area (26 cm(2)). The
      schizophrenic patients and normal university students were asked to draw either a
      horizontal or a vertical line to divide each rectangle at the most aesthetically
      pleasing location. Results. Both the schizophrenic patients and the normal
      university students tended to divide the rectangles into symmetric parts. This
      finding suggests that both groups prefer symmetry, in accordance with the Gestalt
      of Pragnanz, which states that symmetrical figures represent regularity and
      simplicity, and that people tend to prefer "good figures". Compared with normal
      university students, however, schizophrenic patients preferred extremely
      symmetrical figures to asymmetrical figures. Conclusion. We suggest that
      schizophrenic patients' extreme preference for symmetry reflects their generally
      static stances and poor flexibility, as well as a defect in their ability to
      synthesize a whole object from its parts. 

PMID- 24916735
TI  - Follow-up psychotherapy outcome of patients with dependent, avoidant and
      obsessive-compulsive personality disorders: A meta-analytic review.
AB  - Assessing the number of patients who maintain their gains after the completion of
      therapy has been of interest to psychotherapy outcome researchers. The current
      study examines evidence related to the maintenance of treatment gains in
      individuals diagnosed with Cluster C personality disorders. Fifteen studies,
      published between 1982 and 2006, met the criteria for inclusion. The effect size
      standardized mean difference statistic was applied. In the majority of cases,
      most of the improvement occurred between pretreatment and posttreatment. However,
      social skills training often produced effect sizes that were larger for
      posttreatment follow-up. The study indicates that therapy gains are usually
      maintained at follow-up for Cluster C clients treated with cognitive-behavioral
      and psychodynamic approaches as well as social skills training. Uncertainty
      remains whether DPD, AVPD or OCPD patients benefited most from therapy. 

PMID- 24916737
TI  - Erratum to: The significance of osteitis in rhinosinusitis.

PMID- 24916736
TI  - How does parental smoking affect nasal mucociliary clearance in children?
AB  - Correlation between passive smoking and nasal mucociliary clearance (MCC) in
      pediatric population has not been reported before. Therefore, in this study, we
      aimed to investigate the relationship between environmental tobacco smoke and
      nasal MCC in children whose parents smoke in or outside the house. Three groups
      of subjects were evaluated: control group (group 1) with 18 children who were not
      exposed to environmental smoke, 15 passive smokers living with at least one adult
      household member smoking outside the house (group 2), 17 passive smokers living
      with at least one adult household member smoking inside the house (group 3).
      Parents of children were asked to answer our questions regarding their smoking
      history, and nasal MCC time was assessed for all individuals of the 3 groups. The
      mean MCC value in control group, group 2 and group 3 were 7.33 +/- 2.91, 10.00 +/
      4.78 and 12.41 +/- 3.44, respectively. Differences between the mean nasal MCC
      values of the groups were statistically significant (p < 0.01). The comparison of
      MCC values between control group and group 2 did not reveal significant
      difference, but since p value was very close to significance level, in larger
      series it could be significant. (p = 0.067). Also, when we compared the MCC
      values between group 2 and group 3, there was no significant difference (p =
      0.173). But, the difference between MCC values of control group and group 3 was
      statistically significant (p < 0.001). Parental smoking both inside or outside
      the house seemed to increase nasal mucociliary clearance time when they are
      compared with healthy controls. Further studies with larger study groups also
      measuring direct quantitative doses of smoking are needed to verify this
      important issue.

PMID- 24916738
TI  - Is there a relationship between objective and subjective assessment of balance in
      elderly patients with instability?
AB  - To assess whether a subjective questionnaire that measures the disability caused
      by balance disorders in daily life activities is correlated to objective
      assessment of balance in elderly patients with age-related instability. We
      included 37 subjects aged 65 years or more who presented balance disorders
      induced solely by age. Balance assessment was through the sensory organisation
      test and limits of stability of computerised dynamic posturography, the SwayStar
      system and the modified timed up and go test. The patients also completed the
      dizziness handicap inventory (DHI) questionnaire. The SwayStar balance control
      index (BCI) was most significantly correlated to the DHI score and the score of
      its different scales. When we divided the patients into subgroups according to
      DHI score, we only found statistically significant differences in the BCI and
      number of falls. In our population of elderly patients with instability, there is
      practically no correlation between the DHI and the static balance assessment.
      However, there is greater correlation with the BCI, which could show that dynamic
      balance is perceived as more disabling for these patients. In this case, when
      designing a rehabilitation protocol we should focus more on dynamic activities
      such as gait.

PMID- 24916739
TI  - A group-specific arbitrary tradition in chimpanzees (Pan troglodytes).
AB  - Social learning in chimpanzees has been studied extensively and it is now widely
      accepted that chimpanzees have the capacity to learn from conspecifics through a
      multitude of mechanisms. Very few studies, however, have documented the existence
      of spontaneously emerged traditions in chimpanzee communities. While the rigour
      of experimental studies is helpful to investigate social learning mechanisms,
      documentation of naturally occurring traditions is necessary to understand the
      relevance of social learning in the real lives of animals. In this study, we
      report on chimpanzees spontaneously copying a seemingly non-adaptive behaviour
      ("grass-in-ear behaviour"). The behaviour entailed chimpanzees selecting a stiff,
      straw-like blade of grass, inserting the grass into one of their own ears,
      adjusting the position, and then leaving it in their ear during subsequent
      activities. Using a daily focal follow procedure, over the course of 1 year, we
      observed 8 (out of 12) group members engaging in this peculiar behaviour.
      Importantly, in the three neighbouring groups of chimpanzees (n = 82), this
      behaviour was only observed once, indicating that ecological factors were not
      determiners of the prevalence of this behaviour. These observations show that
      chimpanzees have a tendency to copy each other's behaviour, even when the
      adaptive value of the behaviour is presumably absent. 

PMID- 24916740
TI  - The relationship between posttraumatic stress and posttraumatic growth among
      adolescent and young adult (AYA) cancer patients.
AB  - OBJECTIVE: Theories of posttraumatic growth suggest that some degree of distress
      is necessary to stimulate growth; yet, investigations of the relationship between
      stress and growth following trauma are mixed. This study aims to understand the
      relationship between posttraumatic stress symptoms and posttraumatic growth in
      adolescent and young adult (AYA) cancer patients. METHOD: 165 AYA patients aged
      14-39 years at diagnosis completed standardized measures of posttraumatic stress
      and posttraumatic growth at 12 months following diagnosis. Locally weighted
      scatterplot smoothing and regression were used to examine linear and curvilinear
      relationships between posttraumatic stress and posttraumatic growth. RESULTS: No
      significant relationships between overall posttraumatic stress severity and
      posttraumatic growth were observed at 12-month follow-up. However, curvilinear
      relationships between re-experiencing (a posttraumatic stress symptom) and two of
      five posttraumatic growth indicators (New Possibilities, Personal Strengths) were
      observed. CONCLUSION: Findings suggest that re-experiencing is associated with
      some aspects of posttraumatic growth but not others. Although re-experiencing is
      considered a symptom of posttraumatic stress disorder, it also may represent a
      cognitive process necessary to achieve personal growth for AYAs. Findings call
      into question the supposed psychopathological nature of re-experiencing and
      suggest that re-experiencing, as a cognitive process, may be psychologically
      adaptive. Opportunities to engage family, friends, cancer survivors, or health
      care professionals in frank discussions about fears, worries, or concerns may
      help AYAs re-experience cancer in a way that enhances their understanding of what
      happened to them and contributes to positive adaptation to life after cancer.

PMID- 24916742
TI  - Temperature variability and childhood pneumonia: an ecological study.
AB  - BACKGROUND: Few data on the relationship between temperature variability and
      childhood pneumonia are available. This study attempted to fill this knowledge
      gap. METHODS: A quasi-Poisson generalized linear regression model combined with a
      distributed lag non-linear model was used to quantify the impacts of diurnal
      temperature range (DTR) and temperature change between two neighbouring days
      (TCN) on emergency department visits (EDVs) for childhood pneumonia in Brisbane,
      from 2001 to 2010, after controlling for possible confounders. RESULTS: An
      adverse impact of TCN on EDVs for childhood pneumonia was observed, and the
      magnitude of this impact increased from the first five years (2001-2005) to the
      second five years (2006-2010). Children aged 5-14 years, female children and
      Indigenous children were particularly vulnerable to TCN impact. However, there
      was no significant association between DTR and EDVs for childhood pneumonia.
      CONCLUSIONS: As climate change progresses, the days with unstable weather pattern
      are likely to increase. Parents and caregivers of children should be aware of the
      high risk of pneumonia posed by big TCN and take precautionary measures to
      protect children, especially those with a history of respiratory diseases, from
      climate impacts.

PMID- 24916741
TI  - Oral exposure of pubertal male mice to endocrine-disrupting chemicals alters fat
      metabolism in adult livers.
AB  - The potential for the exposure of humans and wildlife to environmental endocrine
      disrupting chemicals (EDCs) has been increasing. Risk assessment for such EDCs is
      primarily based on detecting the main endpoints related to the endocrine and
      reproductive systems, while the effects on glucose and fat metabolism have only
      received limited attention. In this study, pubertal male C57BL/6J mice were
      orally administered 10 mg/kg body weight cypermethrin (CYP), 100 mg/kg body
      weight atrazine (ATZ), and 0.1 mg/kg body weight 17alpha-ethynyestradiol (EE2)
      for 4 weeks and then switched to a high-energy diet (HD) for 8 weeks. The body
      weight gain in the EDC-treated groups was lower than that in the control group
      during exposure and then tended to show values similar to the HD group. The
      epididymal fat weight, cell size and serum triacylglycerol (TG) and total
      cholesterol (TCH) levels in the EDC-HD groups were lower than those in the HD
      group. The transcription of genes related to glycolytic and gluconeogenic
      processes in the liver was affected by EDC exposure. Furthermore, the expression
      levels of transcriptional factors including PPARalpha, PPARgamma, and SREBP1C and
      their target genes related to fatty acid synthesis and oxidation in the liver
      were also influenced by early life EDC administration. The results showed that
      early-life-stage exposure to high doses of various environmental EDCs affected
      the homeostasis of glucose and fatty acid metabolism in the livers of adult male
      mice.

PMID- 24916743
TI  - New workforce development in dementia care: screening for "caring": preliminary
      data.
AB  - The United States has a significant shortage of trained geriatricians and of
      nurses, social workers, and paraprofessionals educated to care for elderly
      adults. As the aging population continues to grow, providing high-quality care
      will require new models that better address the many needs of aging individuals
      and their caregivers, using cost-effective strategies. Responding to this need,
      the Indiana University Center for Aging Research implementation scientists
      developed, tested, and are now scaling up a successful collaborative care
      coordination model for older adults with dementia, depression, or both: the Aging
      Brain Care program. This model now includes a newly created frontline care
      provider position, the Care Coordinator Assistant. The Care Coordinator Assistant
      works with individuals and caregivers to monitor biopsychosocial needs and
      deliver evidence-based and individualized care protocols, with close supervision
      from the registered nurse Care Coordinator. Recognizing that current hiring
      practices for frontline providers were insufficient to screen for critical
      abilities expected in this new position, including the ability to express
      "caring" and empathy, a new screening process was created building on the
      Multiple Mini Interview (MMI) format. The Care Coordinator Assistant MMI
      comprised six stations, each created to simulate challenging scenarios that will
      be frequently encountered and to assess important candidate abilities. Overall,
      the six-station MMI, with two to three items per station, provided factorially
      valid measures and good predictive ability. The process did not appear to be
      overly burdensome for candidates, and interviewers noted that it was helpful in
      discriminating between candidates. 

PMID- 24916744
TI  - The clinical behavior of transplantable recurrent hepatocellular carcinoma after
      curative resection: implications for salvage liver transplantation.
AB  - BACKGROUND: This study aimed to classify transplantable recurrent hepatocellular
      carcinoma (HCC) after resection into subgroups according to the pattern of
      progression and to identify risk factors for each subgroup to select optimal
      candidates for salvage liver transplantation (LT). METHODS: The patients that met
      the Milan criteria (MC) and were child-pugh class A at initial hepatectomy were
      included in the study. Of these patients, the patients with transplantable
      recurrence were identified and further divided into two groups according to the
      recurrent HCC progression pattern. Group 1 contained patients with controlled
      tumors within the MC. Group 2 contained patients with progressive tumors that
      spread beyond the MC. A controlled tumor was defined as the absence of tumor
      recurrence after locoregional treatment for >=12 months or control of a recurrent
      tumor within the MC by active locoregional treatment. RESULTS: After curative
      resection of HCC, 114 patients with transplantable recurrence were identified: 70
      were classified as group 1 and 44 as group 2. Overall survival after recurrence
      was significantly higher in group 1 compared to group 2 (65.4 vs 35.7 %,
      respectively; P < 0.003). Multiple logistic regression analysis showed that risk
      factors in group 1 were age >50 years and an indocyanine green retention at 15
      min >10 %. The presence of a satellite nodule (SN) and/or microscopic portal vein
      invasion (mPVI) was the only independent risk factor identified in group 2. Among
      the 15 patients that underwent salvage LT, 2 of 3 patients (66.7 %) with SN
      and/or mPVI at initial hepatectomy developed extrahepatic recurrence.
      CONCLUSIONS: The patients with SN and/or mPVI at initial hepatectomy may not be
      candidates for salvage LT, and an extended observation time is required to
      determine tumor biology.

PMID- 24916746
TI  - Surgical resection after down-staging of locally advanced hepatocellular
      carcinoma by localized concurrent chemoradiotherapy.
AB  - BACKGROUND: This study evaluated the down-staging efficacy and impact on
      resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial
      infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and
      identified prognostic factors of disease-free survival (DFS) and overall survival
      (OS) after curative resection. METHODS: DFS and OS were investigated using
      clinicopathologic variables. Functional residual liver volume (FRLV) was assessed
      before CCRT and again before surgery in patients with major hepatectomy. Tumor
      marker response was defined as elevated tumor marker levels at diagnosis but
      levels below cutoff values before surgery (alpha-fetoprotein < 20 ng/mL, protein
      induced by vitamin K absence or antagonist-II < 40 mAU/mL). RESULTS: Of 243
      patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %)
      underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of
      the resected patients. FRLV significantly increased from 47.5 to 69.9 % before
      surgery in patients who underwent major hepatectomy. In addition, the OS of the
      curative resection group was significantly higher than the OS of the CCRT
      followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By
      multivariate analysis, the poor prognostic factors for DFS after curative
      resection were tumor marker non-response and the presence of a satellite nodule;
      however, tumor marker non-response was the only independent poor prognostic
      factor of OS. CONCLUSIONS: CCRT followed by HAIC increased resectability by down
      staging tumors and increasing FRLV. Curative resection may provide good long-term
      survival in tumor marker responders who undergo CCRT followed by HAIC.

PMID- 24916745
TI  - Prognostic impact of CA 19-9 on outcome after neoadjuvant chemoradiation in
      patients with locally advanced pancreatic cancer.
AB  - BACKGROUND: To asses the impact of CA 19-9 and weight loss/gain on outcome after
      neoadjuvant chemoradiation (CRT) in patients with locally advanced pancreatic
      cancer (LAPC). METHODS: We analyzed 289 patients with LAPC treated with CRT for
      LAPC. All patients received concomitant chemotherapy parallel to radiotherapy and
      adjuvant treatments. CA 19-9 and body weight were collected as prognostic and
      predictive markers. All patients were included into a regular follow-up with
      reassessment of resectability. RESULTS: Median overall survival in all patients
      was 14 months. Actuarial overall survival was 37 % at 12 months, 12 % at 24
      months, and 4 % at 36 months. Secondary resectability was achieved in 35 % of the
      patients. R0/R1 resection was significantly associated with increase in overall
      survival (p = 0.04). Intraoperative radiotherapy was applied in 50 patients, but
      it did not influence overall survival (p = 0.05). Pretreatment CA 19-9
      significantly influenced overall survival using different cutoff values. With
      increase in CA 19-9 levels, the possibility of secondary surgical resection
      decreased from 46 % in patients with CA 19-9 levels below 90 U/ml to 31 % in the
      group with CA 19-9 levels higher than 269 U/ml. DISCUSSION: This large group of
      patients with LAPC treated with neoadjuvant CRT confirms that CA 19-9 and body
      weight are strong predictive and prognostic factors of outcome. In the future,
      individual patient factors should be taken into account to tailor treatment.

PMID- 24916747
TI  - Does obesity affect outcomes of cytoreductive surgery and hyperthermic
      intraperitoneal chemoperfusion for disseminated mucinous appendiceal neoplasms?
AB  - BACKGROUND: Obesity has been described as a risk factor for surgical
      complications and may play a prominent role in the progression, recurrence, and
      survival rates of various cancers. Our objective was to investigate the impact of
      being overweight or obese on perioperative and oncologic outcomes after
      cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion
      (HIPEC) for peritoneal carcinomatosis (PC) from mucinous appendiceal neoplasms
      (MAN). METHODS: From a prospectively maintained database (2001-2010) of CRS/HIPEC
      for PC from MAN, we evaluated the body mass index (BMI) of patients, categorizing
      them into normal weight (NW < 25 kg/m(2)), overweight (OW = 25 to 29.9 kg/m(2)),
      and obese (OB >= 30 kg/m(2)). We compared the perioperative and oncologic
      outcomes among groups. RESULTS: Of the 282 patients in the database, 234 had BMI
      data available, and 81, 79, and 74 patients were categorized as NW, OW, and OB,
      respectively. Although there was a trend toward increased risk of overall
      complications, wound infections, deep vein thrombosis, respiratory and renal
      complications, and anastomotic leaks in the OW and OB groups, these differences
      only achieved statistical significance for renal (p = 0.03) and pulmonary (p =
      0.02) complications in the OW and OB groups, respectively. The 5-year survival
      rate for NW, OW, and OB patients was 63.9, 48, and 54.4 %, respectively (p =
      0.63). The median time to progression was 21.1 (NW), 21.7 (OW), and 23.9 (OB)
      months (p = 0.83). CONCLUSIONS: OW and OB patients may have an increased risk of
      renal and pulmonary complications, respectively. Obesity has no major impact on
      perioperative mortality and long-term oncologic outcomes in patients undergoing
      CRS/HIPEC for MAN.

PMID- 24916749
TI  - Thoracopulmonary actinomycosis, a case report of a 42-year-old man with coughing
      and a bump in his right axilla.
AB  - The diagnosis of thoracopulmonary actinomycosis is challenging because it is a
      rare disease, symptoms are aspecific and can mimic a lot of other lung
      pathologies. Especially the differential diagnosis with pulmonary tuberculosis is
      difficult because clinical symptoms are often very similar. We present a case of
      thoracopulmonary abcedating actinomycosis in a young immunocompetent man with no
      predisposing illness. He was initially treated for pulmonary tuberculosis. He
      showed good response to IV penicillin, which was later switched to oral
      amoxicillin when he went home. 

PMID- 24916748
TI  - Use of synthetic cathinones and cannabimimetics among injection drug users in San
      Diego, California.
AB  - BACKGROUND: Use of synthetic cathinones (SC) and cannabimimetics (i.e., "THC
      homologues" [TH]) is associated with adverse health effects. We investigated the
      epidemiology of synthetic drug use among a cohort of injection drug users (IDUs)
      in San Diego, California. METHODS: We used logistic regression analysis to
      identify correlates of SC and TH use among 485 IDUs enrolled from June 2012 to
      September 2013. RESULTS: Seven percent of participants reported ever using SC and
      30% reported ever using TH. In multivariate logistic regression, age and recent
      hospitalization were significantly associated with odds of SC use (Adjusted Odds
      Ratio [AOR] 0.93, 95% Confidence Interval [C.I.] 0.90, 0.97; and AOR 2.34 95%
      C.I. 1.00, 5.49, respectively) and TH use (AOR 0.96, 95% C.I. 0.94, 0.98; and AOR
      2.62, 95% C.I. 1.47, 4.68, respectively). Use of methamphetamine (AOR 9.35, 95%
      C.I. 1.20, 72.79) and club drugs in the past six months (AOR 3.38, 95% C.I. 1.17,
      9.76) were significantly associated with SC use. Being on probation/parole (AOR
      2.42, 95% C.I. 1.44, 4.07), initiating injection drug use with stimulants (AOR
      1.89 95% C.I. 1.13, 3.16), and past six-month marijuana (AOR 9.22, 95% C.I. 4.49,
      18.96) and prescription drug use (AOR 1.98, 95% C.I. 1.20, 3.27) were
      significantly associated with TH use. CONCLUSIONS: A considerable proportion of
      IDU use synthetic drugs and may experience harms associated with their use.
      Findings have implications for criminal justice system management. Prevention
      efforts should emphasize the risks associated with rapidly changing synthetic
      formulations, and the potential harms associated with polydrug use.

PMID- 24916750
TI  - Postprandial reactive hypoglycaemia in a very old patient.
AB  - OBJECTIVE AND IMPORTANCE: Postprandial reactive hypoglycaemia (PRH) is a clinical
      syndrome characterized by the recurrence of symptomatic hypoglycaemia during
      postprandial periods. PRH remains a diagnostic challenge for clinicians, because
      of its atypical manifestations and low prevalence, especially in older persons.
      CLINICAL PRESENTATION: We report the diagnostic work-up of severe hypoglycaemic
      episodes in a very old patient in whom the diagnosis of PRH was made.
      INTERVENTION: We prescribed acarbose, an alpha-glucosidase inhibitor, to this
      patient to prevent the recurrence of hypoglycaemic episodes. Four years later,
      acarbose was always used and no further episode of hypoglycaemia had occurred.
      Based on the literature, we discuss the limited value of endocrine tests as well
      as the efficacy of the therapeutic approaches. CONCLUSION: Prescription of
      acarbose is useful in addition to nutritional education, the corner stone of the
      treatment, to avoid the recurrence of severe hypoglycaemic events due to PRH.

PMID- 24916751
TI  - Epstein-Barr virus serology and PCR: conflicting results in an immunocompetent
      host. A case report and review of literature.
AB  - We present the case of a 27-year-old immunocompetent man who progressively
      developed a generalized lymphadenopathy and B symptoms. Results of Epstein-Barr
      virus (EBV) serology were suggestive for a past infection, but the EBV viral load
      in whole blood was high. Also, core needle biopsy of the largest lymph node
      showed an image which could fit an EBV-driven reactive lymphoproliferation.
      Despite the absence of an immune disorder, all medical evidence points to an EBV
      driven lymphoproliferative proces. In immunocompetent patients, it seems
      extremely uncommon to detect a high EBV viral load in the absence of serological
      evidence of an acute EBV infection or reactivation. We reviewed literature on
      this topic and on the selection of the appropriate sample type for EBV PCR, as
      this is known to be a critical point. Serological testing for the diagnosis of
      EBV infection is the gold standard in immunocompetent patients. Measuring EBV
      viral load is only recommended when dealing with immunocompromised patients.
      Although extremely rare, this case report shows that there is a place for EBV PCR
      in certain situations in immunocompetent patients. Besides, there is still no
      consensus regarding the specimen of choice for the determination of the EBV viral
      load. The preferred specimen type seems to depend on the patient's underlying
      condition. 

PMID- 24916752
TI  - Laboratory diagnosis of schistosomiasis and Katayama syndrome in returning
      travellers.
AB  - The gold standard for laboratory diagnosis of schistosomiasis is the presence of
      typical eggs in stool or urine. The laboratory diagnosis of schistosomiasis and
      Katayama syndrome in returning travellers is difficult because the number of
      excreted eggs is often very limited. In early infections and in patients with
      only a few contacts with contaminated water, the total number of parasites,
      migrating larvae or schistosomulae, and adult worms, is very low. Eggs can only
      be found in faeces or urine when there is at least one pair of adult worms at the
      final location. The number of parasites increases as a function of the number of
      contacts with infected water. The exact latency between contamination and egg
      production is unknown. It is estimated that excretion of eggs starts after 40-50
      days. The specific diagnosis of early schistosomiasis and Katayama fever relies
      essentially on serologic tests or preferably on PCR (if available). These assays
      are much more sensitive (up to four times) in the early phase of schistosomiasis
      than microscopic examination for typical eggs. Eosinophilia (sometimes exceeding
      50%) is often present in patients with acute schistosomiasis (Katayama fever),
      but may be limited or absent in late fibrotic manifestations of the disease. 

PMID- 24916753
TI  - Sleep in the Intensive Care Unit: A Review.
AB  - Patients in the intensive care unit (ICU) are susceptible to sleep deprivation.
      Disrupted sleep is associated with increased morbidity and mortality in the
      critically ill patients. The etiology of sleep disruption is multifactorial. The
      article reviews the literature on sleep in the ICU, the effects of sleep
      deprivation, and strategies to promote sleep in the ICU. Until the impact of
      disrupted sleep is better explained, it is appropriate to provide critically ill
      patients with consolidated, restorative sleep. 

PMID- 24916754
TI  - Evaluation of the Clinical Utility of Routine Daily Chest Radiography in
      Intensive Care Unit Patients With Tracheostomy Tubes: A Retrospective Review.
AB  - BACKGROUND: The utilization of imaging procedures is under scrutiny due to high
      costs and radiation exposure to patients and staff associated with some
      radiologic procedures. Within our institution's intensive care unit (ICU), it is
      common for patients to undergo chest radiography (CR) not only immediately
      following tracheostomy tube placement but also on a daily basis, irrespective of
      the patient's clinical status. We hypothesize that the clinical utility of
      performing routine daily CR on patients with tracheostomy tubes is low and leads
      to unnecessary financial cost. METHODS: A retrospective medical chart review was
      done on 761 CRs performed on 79 ICU patients with tracheostomy from April 2010 to
      July 2011. We searched the radiology reports of the 761 CRs for the presence of
      new radiographically detected complications and reviewed medical records to
      determine which complications were clinically suspected and which radiology
      reports led to changes in patient management. RESULTS: Of the 761 CRs, only 18
      (2.3%) radiographs revealed new complications. All complications were clinically
      suspected prior to imaging. Only 5 (0.7%) complications resulted in a management
      change. The most common management changes were a change in antibiotic regimen
      (0.3%) and ordering of diuretics (0.3%). CONCLUSIONS: Routine daily imaging of
      patients with tracheostomy in an ICU provides little clinical utility, and CR in
      this population should be performed selectively based on the patient's clinical
      status.

PMID- 24916755
TI  - Characteristics and Outcomes of Ethics Consultations in an Oncologic Intensive
      Care Unit.
AB  - OBJECTIVE: To evaluate the frequency, characteristics, and outcomes of ethics
      consultations in critically ill patients with cancer. DESIGN, SETTING, AND
      METHODS: This is a retrospective analysis of all adult patients with cancer who
      were admitted to the intensive care unit (ICU) of a comprehensive cancer center
      and had an ethics consultation between September 2007 and December 2011.
      Demographic and clinical variables were abstracted along with the details and
      contexts of the ethics consultations. MAIN RESULTS: Ethics consultations were
      obtained on 53 patients (representing 1% of all ICU admissions). The majority
      (90%) of patients had advanced-stage malignancies, had received oncologic
      therapies within the past 12 months, and required mechanical ventilation and/or
      vasopressor therapy for respiratory failure and/or severe sepsis. Two-thirds of
      the patients lacked decision-making capacity and nearly all had surrogates. The
      most common reasons for ethics consultations were disagreements between the
      patients/surrogates and the ICU team regarding end-of-life care. After ethics
      consultations, the surrogates agreed with the recommendations made by the ICU
      team on the goals of care in 85% of patients. Moreover, ethics consultations
      facilitated the provision of palliative medicine and chaplaincy services to
      several patients who did not have these services offered to them prior to the
      ethics consultations. CONCLUSION: Our study showed that ethics consultations were
      helpful in resolving seemingly irreconcilable differences between the ICU team
      and the patients' surrogates in the majority of cases. Additionally, these
      consultations identified the need for an increased provision of palliative care
      and chaplaincy visits for patients and their surrogates at the end of life.

PMID- 24916756
TI  - Dermatologic therapy in geriatric patients.
AB  - Demographic changes in our society will lead to an increasing proportion of
      elderly people. Age-associated multimorbidity often results in polypharmacy and
      elevates the risk of adverse drug reactions. Decisive alterations in
      pharmacokinetics and pharmacodynamics are detectable in old age, primarily a
      decrease in total body water, an altered ratio of muscle mass to fatty tissue,
      and decreased renal function. Changes in gastrointestinal transit, plasma protein
      binding, hepatic drug metabolism, and an increased susceptibility to drug-induced
      cognitive decompensation have also been reported. All these alterations should be
      considered in geriatric dermatotherapy to minimize drug-related complications
      caused by over- or underdosage and drug interactions. 

PMID- 24916757
TI  - Liver failure and transplantation after duodenal switch.
AB  - Liver failure (LF) and liver transplant (LT) are rare after a biliopancreatic
      diversion/duodenal switch procedure for obesity, but occasionally it may happen.
      Two clinical cases are presented. One patient, 18 years ago, had LF, but a liver
      donor could not be found, and the patient died. The second patient, 2 years ago,
      received a successful LT and is now well and asymptomatic. Careful follow-up,
      medical management and surgical intervention may prevent the occurrence of LF.
      Transplantation and bowel reversal may be necessary. 

PMID- 24916758
TI  - Simultaneous enhancement of excitation and postburst inhibition at the end of
      focal seizures.
AB  - OBJECTIVE: Comprehension of the events that lead to seizure termination
      contributes to the development of strategies to confine propagation of ictal
      discharges. It is commonly assumed that the inhibitory control fails during
      seizures and recovers after the end of the ictal event. We examine the
      possibility that a progressive increase of inhibition that counters an increase
      in the strength of excitation contributes to terminating a focal seizure.
      METHODS: We analyzed seizures acutely induced by pharmacological manipulations
      (bicuculline and 4-aminopyridine) in the entorhinal cortex and in the hippocampus
      of the in vitro isolated guinea pig brain. RESULTS: As seizures ended,
      extracellular and intracellular recordings showed periodic bursting that
      progressively decreased in frequency. During the late bursting phase, the
      duration, number, and rate of occurrence of spikes within single bursts remained
      constant, whereas cumulative spike amplitude (index of excitation during a burst)
      and interburst interval (index of inhibition between bursts) progressively
      increased. The increment of average/cumulative burst excitation and interburst
      interval toward seizure end was confirmed in human focal seizures recorded with
      intracerebral electrodes in patients with drug-resistant partial epilepsies. A
      postburst refractory period of circa 2 seconds that increases with time toward
      the end of the seizure was confirmed in the experimental model by probing
      interburst epochs in the CA1 region with local dentate gyrus stimulation just
      suprathreshold for burst generation. INTERPRETATION: Our findings support the
      concept that focal seizures are terminated by the simultaneous and opposing
      enhancement of excitation (burst activity) in addition to postburst inhibition.
      We hypothesize that a seizure stops when postburst inhibition becomes large
      enough to prevent reactivation of excitation.

PMID- 24916759
TI  - Population genetic data and forensic parameters of 30 autosomal InDel markers in
      Santa Catarina State population, Southern Brazil.
AB  - The application of DNA technology in forensic investigations has grown rapidly in
      the last 25 years and with an exponential increase of short tandem repeats (STRs)
      data, usually presented as allele frequencies, that may be later used as
      databases for forensic and population genetics purposes. Thereby, classes of
      molecular markers such as single nucleotide polymorphisms and
      insertions/deletions (InDels) have been presented as another option of genetic
      marker sets. These markers can be used in paternity cases, when mutations in STR
      polymorphisms are present, as well as in highly degraded DNA analysis. In the
      present study, the allele frequencies and heterozygosity (H) of a 30 InDel
      markers set were determined and the forensic efficacy was evaluated through
      estimation of discrimination power (DP), match probability, typical paternity
      index and power of paternity exclusion in 108 unrelated volunteers from the State
      of Santa Catarina (South Brazil). The observed H per locus showed a range between
      0.370 and 0.574 (mean = 0.479). HLD128 was the locus with the highest DP (DP =
      0.656). DP for all markers combined was greater than 99.9999999999646 % which
      provides satisfactory levels of information for forensic demands. Genetic
      comparisons (exact tests of population differentiation and pairwise genetic
      distances) revealed that the population of Santa Catarina State differs from
      Korea and USA Afro-American populations but is similar to the Portuguese, German,
      Polish, Spanish and Basque populations.

PMID- 24916760
TI  - American Cancer Society prostate cancer survivorship care guidelines.
AB  - Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of
      all cancer survivors in the United States. While guidelines exist for timely
      treatment and surveillance for recurrent disease, there is limited availability
      of guidelines that facilitate the provision of posttreatment clinical follow-up
      care to address the myriad of long-term and late effects that survivors may face.
      Based on recommendations set forth by a National Cancer Survivorship Resource
      Center expert panel, the American Cancer Society developed clinical follow-up
      care guidelines to facilitate the provision of posttreatment care by primary care
      clinicians. These guidelines were developed using a combined approach of evidence
      synthesis and expert consensus. Existing guidelines for health promotion,
      surveillance, and screening for second primary cancers were referenced when
      available. To promote comprehensive follow-up care and optimal health and quality
      of life for the posttreatment survivor, the guidelines address health promotion,
      surveillance for prostate cancer recurrence, screening for second primary
      cancers, long-term and late effects assessment and management, psychosocial
      issues, and care coordination among the oncology team, primary care clinicians,
      and nononcology specialists. A key challenge to the development of these
      guidelines was the limited availability of published evidence for management of
      prostate cancer survivors after treatment. Much of the evidence relies on studies
      with small sample sizes and retrospective analyses of facility-specific and
      population databases.

PMID- 24916761
TI  - AglB, catalyzing the oligosaccharyl transferase step of the archaeal N
      glycosylation process, is essential in the thermoacidophilic crenarchaeon
      Sulfolobus acidocaldarius.
AB  - Sulfolobus acidocaldarius, a thermo-acidophilic crenarchaeon which grows
      optimally at 76  degrees C and pH 3, exhibits an astonishing high number of N
      glycans linked to the surface (S-) layer proteins. The S-layer proteins as well
      as other surface-exposed proteins are modified via N-glycosylation, in which the
      oligosaccharyl transferase AglB catalyzes the final step of the transfer of the
      glycan tree to the nascent protein. In this study, we demonstrated that AglB is
      essential for the viability of S. acidocaldarius. Different deletion approaches,
      that is, markerless in-frame deletion as well as a marker insertion were
      unsuccessful to create an aglB deletion mutant. Only the integration of a second
      aglB gene copy allowed the successful deletion of the original aglB.

PMID- 24916762
TI  - Serum amyloid A and haptoglobin concentrations are increased in plasma of mares
      with ascending placentitis in the absence of changes in peripheral leukocyte
      counts or fibrinogen concentration.
AB  - PROBLEM: Currently, placentitis, an important cause of late pregnancy loss in
      mares, is diagnosed by clinical signs and ultrasonography. Acute phase proteins
      (APP) are mainly produced and secreted by the liver in response to acute
      inflammatory stimuli. We hypothesized that APP are increased in mares with
      placentitis. METHOD OF STUDY: Concentrations of serum amyloid A (SAA),
      haptoglobin (Hp), fibrinogen (Fb), and white blood cell counts (WBC) were
      determined in plasma of mares with experimentally induced placentitis and
      gestationally age-matched control mares. Placentitis was induced via
      intracervical inoculation of Streptococcus equi subspecies zooepidemicus, a
      common isolate from clinical cases of bacterial placentitis. Concentrations of
      SAA and Hp were also determined in the 10 days pre-partum in normal mares.
      RESULTS AND CONCLUSION: Mares with placentitis aborted within 5-25 days after
      inoculation. Concentrations of SAA and Hp rapidly increased subsequent to
      experimental induction of placentitis and remained increased until abortion.
      Neither Fb nor WBC appeared to be useful markers for placentitis. Parturition did
      not trigger increase in either SAA or Hp in normal foaling mares.

PMID- 24916763
TI  - Is retrograde flexible nephrolithotripsy feasible for calyceal diverticular
      stone?
AB  - The aim of this study is to manage the calyceal diverticular (CD) stone, several
      treatment options were applied but it is still a challenging condition of
      endourology. In this retrospective study, we aim to report the results of our
      patients with CD stones treated with retrograde flexible nephrolithotripsy
      (RFNL). A total of 47 patients (55 procedures) who underwent RFNL by a single
      surgeon for CD stones from January 2004 to March 2013 were evaluated
      retrospectively. The demographic properties and initial complaints of those
      patients have been recorded along with their comorbidities and previous history
      of stone management. Moreover, the size and number of the stones, the duration of
      the surgery, fluoroscopy time, stone-free rate (SFR) and postoperative
      complications of the patients have been evaluated. The mean age was 41.8 years
      (range 16-71). Of the study population, 31 (65.9%) were male. Mean stone size was
      21.1 (7-52) mm whereas in 3 (6.4%) of the cases the stones could not be reached.
      Mean duration of the surgery was 92.8 (57-163) min whereas mean fluoroscopy time
      was 35.9 (14-103) s. After 3 months of follow-up period, the SFR was 85.1%. No
      major complications occurred. RFNL with holmium laser and nitinol basket catheter
      application is a feasible and successful procedure in the management of CD
      stones. With its high success rates, low incidence of complications and minimal
      morbidity when compared with other treatment options, RFNL has the potential of
      becoming the preferred treatment option in the minimally invasive management of
      patients with CD stones.

PMID- 24916764
TI  - An investigation into dental anxiety amongst paediatric cardiology patients.
AB  - BACKGROUND: There is evidence that children with cardiac conditions have high
      levels of untreated dental disease. One possible explanation is that they are
      more dentally anxious as a result of increased exposure to medical interventions.
      Therefore, the primary aim of this study was to compare the level of dental
      anxiety between paediatric cardiology patients and healthy children. METHODS: The
      study group comprised 54 children (mean age 12.2 years) who attended the
      outpatient paediatric cardiology clinic in tertiary care. The control group (n =
      53, mean age 12.38 years) was recruited from consultant-led new-patient
      orthodontic clinics. Child dental anxiety was measured using the Modified Child
      Dental Anxiety Scale (faces version). The parents completed the Modified Dental
      Anxiety Scale along with a questionnaire regarding their child's medical and
      dental histories. RESULTS: The mean level of dental anxiety was significantly
      higher in the study group (P < 0.05). Analysis of covariance indicated that
      overnight hospital admission history may have influenced the strength of this
      relationship. CONCLUSIONS: Paediatric cardiology patients had significantly
      increased levels of dental anxiety. It is likely that aspects of their medical
      history, notably overnight hospital admissions, are contributory factors.

PMID- 24916765
TI  - Longitudinal relations among parents' reactions to children's negative emotions,
      effortful control, and math achievement in early elementary school.
AB  - Panel mediation models and fixed-effects models were used to explore longitudinal
      relations among parents' reactions to children's displays of negative emotions,
      children's effortful control (EC), and children's math achievement (N = 291; M
      age in fall of kindergarten = 5.66 years, SD = .39 year) across kindergarten
      through second grade. Parents reported their reactions and children's EC. Math
      achievement was assessed with a standardized achievement test. First-grade EC
      mediated the relation between parents' reactions at kindergarten and second-grade
      math achievement, beyond stability in constructs across study years. Panel
      mediation model results suggested that socialization of EC may be one method of
      promoting math achievement in early school; however, when all omitted time
      invariant covariates of EC and math achievement were controlled, first-grade EC
      no longer predicted second-grade math achievement.

PMID- 24916766
TI  - Mesenchymal precursor cells maintain the differentiation and proliferation
      potentials of breast epithelial cells.
AB  - INTRODUCTION: Stromal-epithelial interactions play a fundamental role in tissue
      homeostasis, controlling cell proliferation and differentiation. Not
      surprisingly, aberrant stromal-epithelial interactions contribute to
      malignancies. Studies of the cellular and molecular mechanisms underlying these
      interactions require ex vivo experimental model systems that recapitulate the
      complexity of human tissue without compromising the differentiation and
      proliferation potentials of human primary cells. METHODS: We isolated and
      characterized human breast epithelial and mesenchymal precursors from reduction
      mammoplasty tissue and tagged them with lentiviral vectors. We assembled
      heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in
      corresponding monocultures by analyzing growth, differentiation potentials, and
      gene expression profiles. RESULTS: We show that heterotypic culture of non
      immortalized human primary breast epithelial and mesenchymal precursors maintains
      their proliferation and differentiation potentials and constrains their growth.
      We further describe the gene expression profiles of stromal and epithelial cells
      in co-cultures and monocultures and show increased expression of the tumor growth
      factor beta (TGFbeta) family member inhibin beta A (INHBA) in mesenchymal cells
      grown as co-cultures compared with monocultures. Notably, overexpression of INHBA
      in mesenchymal cells increases colony formation potential of epithelial cells,
      suggesting that it contributes to the dynamic reciprocity between breast
      mesenchymal and epithelial cells. CONCLUSIONS: The described heterotypic co
      culture system will prove useful for further characterization of the molecular
      mechanisms mediating interactions between human normal or neoplastic breast
      epithelial cells and the stroma, and will provide a framework to test the
      relevance of the ever-increasing number of oncogenomic alterations identified in
      human breast cancer.

PMID- 24916767
TI  - Transcriptomic analysis of Sorghum bicolor responding to combined heat and
      drought stress.
AB  - BACKGROUND: Abiotic stresses which include drought and heat are amongst the main
      limiting factors for plant growth and crop productivity. In the field, these
      stress types are rarely presented individually and plants are often subjected to
      a combination of stress types. Sorghum bicolor is a cereal crop which is grown in
      arid and semi-arid regions and is particularly well adapted to the hot and dry
      conditions in which it originates and is now grown as a crop. In order to better
      understand the mechanisms underlying combined stress tolerance in this important
      crop, we have used microarrays to investigate the transcriptional response of
      Sorghum subjected to heat and drought stresses imposed both individually and in
      combination. RESULTS: Microarrays consisting of 28585 gene probes identified gene
      expression changes equating to ~4% and 18% of genes on the chip following drought
      and heat stresses respectively. In response to combined stress ~20% of probes
      were differentially expressed. Whilst many of these transcript changes were in
      common with those changed in response to heat or drought alone, the levels of
      2043 specific transcripts (representing 7% of all gene probes) were found to only
      be changed following the combined stress treatment. Ontological analysis of these
      'unique' transcripts identified a potential role for specific transcription
      factors including MYB78 and ATAF1, chaperones including unique heat shock
      proteins (HSPs) and metabolic pathways including polyamine biosynthesis in the
      Sorghum combined stress response. CONCLUSIONS: These results show evidence for
      both cross-talk and specificity in the Sorghum response to combined heat and
      drought stress. It is clear that some aspects of the combined stress response are
      unique compared to those of individual stresses. A functional characterization of
      the genes and pathways identified here could lead to new targets for the
      enhancement of plant stress tolerance, which will be particularly important in
      the face of climate change and the increasing prevalence of these abiotic stress
      types.

PMID- 24916768
TI  - The mono - and sesquiterpene content of aphid-induced galls on Pistacia
      palaestina is not a simple reflection of their composition in intact leaves.
AB  - Pistacia palaestina Boiss. (Anacardiaceae), a sibling species of P. terebinthus
      also known as turpentine tree or terebinth tree, is common in the Levant region.
      The aphid Baizongia pistaciae L. manipulates the leaves of the plant to form
      large galls, which provide both food and protection for its developing offspring.
      We analyzed the levels and composition of mono-and sesquiterpenes in both leaves
      and galls of ten naturally growing trees. Our results show that monoterpene
      hydrocarbons are the main constituents of P. palaestina leaves and galls, but
      terpene levels and composition vary among trees. Despite this inter-tree
      variation, terpene levels and compositions in galls from different trees resemble
      each other more than the patterns displayed by leaves from the same trees.
      Generally, galls contain 10 to 60 fold higher total terpene amounts than leaves,
      especially of the monoterpenes alpha-pinene and limonene. Conversely, the leaves
      generally accumulate more sesquiterpenes, in particular E-caryophyllene,
      germacrene D and delta-cadinene, in comparison to galls. Our results clearly show
      that the terpene pattern in the galls is not a simple reflection of that of the
      leaves and suggest that aphids have a strong impact on the metabolism of their
      host plant, possibly for their own defense. 

PMID- 24916769
TI  - Changes in dopamine transporter binding in nucleus accumbens following chronic
      self-administration cocaine: heroin combinations.
AB  - Concurrent use of cocaine and heroin (speedball) has been shown to exert
      synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc),
      as observed by significant increases in extracellular dopamine levels and
      compensatory elevations in the maximal reuptake rate of dopamine. The present
      studies were undertaken to determine whether chronic self-administration of
      cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in
      the abundance and/or affinity of high- and low-affinity DAT binding sites.
      Saturation binding of the cocaine analog [(125) I] 3beta-(4-iodophenyl)tropan
      2beta-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes
      resulted in binding curves that were best fit to two-site binding models,
      allowing calculation of dissociation constant (Kd ) and binding density (Bmax )
      values corresponding to high- and low-affinity DAT binding sites. Scatchard
      analysis of the saturation binding curves clearly demonstrate the presence of
      high- and low- affinity binding sites in the NAc, with low-affinity sites
      comprising 85 to 94% of the binding sites. DAT binding analyses revealed that
      self-administration of cocaine and a cocaine:heroin combination increased the
      affinity of the low-affinity site for the cocaine congener RTI-55 compared to
      saline. These results indicate that the alterations observed following chronic
      speedball self-administration are likely due to the cocaine component alone; thus
      further studies are necessary to elaborate upon the synergistic effect of
      cocaine:heroin combinations on the dopamine system in the NAc.

PMID- 24916770
TI  - A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family
      inhibitor, in combination with gemcitabine in patients with solid tumors.
AB  - PURPOSE: To investigate the safety, optimal dosing, pharmacokinetics and clinical
      activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in
      patients with solid tumors. EXPERIMENTAL DESIGN: Patients with solid tumors for
      which gemcitabine was deemed an appropriate therapy were enrolled into one of two
      different dosing schedules (21-day dosing schedule: navitoclax administered
      orally on days 1-3 and 8-10,; and gemcitabine 1,000 mg/m(2) on days 1 and 8; 28
      day dosing schedule: navitoclax administrated orally on days 1-3, 8-10, and 15
      17; and gemcitabine 1,000 mg/m(2) on days 1, 8 and 15). Navitoclax doses were
      escalated from 150 to 425 mg. An expanded safety cohort was conducted for the 21
      day dosing schedule at the maximum tolerated dose (MTD) of navitoclax. RESULTS:
      Forty-six patients were enrolled at three U.S. centers. The most common adverse
      events included: hematologic abnormalities (thrombocytopenia, neutropenia, and
      anemia), liver enzyme elevations (ALT and AST), and gastrointestinal disturbances
      (diarrhea, nausea, and vomiting). Dose-limiting toxicities (DLTs) observed in
      cycle 1 were grade 4 thrombocytopenia (2 patients), grade 4 neutropenia (1
      patient), and grade 3 AST elevation (2 patients). The MTD of navitoclax was 325
      mg co-administered with gemcitabine 1,000 mg/m(2) for the 21-day schedule. No
      clinically significant pharmacokinetic drug-drug interactions were observed.
      There were no objective responses. Stable disease, reported at the end of cycle
      2, was the best response in 54 % of evaluable patients (n = 39). CONCLUSIONS: The
      combination of navitoclax 325 mg with gemcitabine 1,000 mg/m(2) was generally
      well tolerated and exhibited a favorable safety profile in patients with advanced
      solid tumors.

PMID- 24916772
TI  - Auricular pyoderma gangrenosum with penetration in a patient with rheumatoid
      arthritis.

PMID- 24916771
TI  - A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic
      colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head
      and neck.
AB  - BACKGROUND: This phase I, dose-finding study determined the safety, maximum
      tolerated dose (MTD)/recommended phase 2 dose (RP2D), and antitumor activity of
      PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with cetuximab in
      patients with incurable colorectal cancer or squamous cell carcinoma of the head
      and neck. METHODS: PX-866 was administered at escalating doses (6-8 mg daily)
      combined with cetuximab given at a 400 mg/m(2) loading dose followed by 250
      mg/m(2) weekly. A "3 + 3" study design was used. Prior therapy with anti-EGFR
      therapies, including cetuximab, was allowed. RESULTS: Eleven patients were
      enrolled. The most frequent treatment-emergent adverse event was diarrhea
      (90.1%), followed by hypomagnesemia (72.2%), vomiting (72.2%), fatigue (54.5%),
      nausea (54.5%), rash (45.5%) and peripheral edema (40%). No dose limiting
      toxicities were observed. The RP2D was 8 mg, the same as the single-agent PX-866
      MTD. Best responses in 9 evaluable patients were: 4 partial responses (44.4%), 4
      stable disease (44.4%), and 1 disease progression (11.1%). The median progression
      free survival was 106 days (range: 1-271). CONCLUSION: Treatment with PX-866 and
      cetuximab was tolerated with signs of anti-tumor activity. Further development of
      this combination is warranted.

PMID- 24916773
TI  - You can't always get what you want: the influence of unexpected task constraint
      on voluntary task switching.
AB  - The current study assessed the effect that unexpected task constraint, following
      self-generated task choice, has on task switching performance. Participants
      performed a modified double-registration voluntary task switching procedure in
      which participants specified the task they wanted to perform, were presented with
      a cue that, on the majority of trials, confirmed the choice, and then performed
      the cued task. On a small portion of trials, participants were cued to perform a
      task that did not match their choice. Trials on which cues unexpectedly failed to
      match the chosen task were associated with costs. These costs were particularly
      large when participants chose to switch tasks but had to unexpectedly repeat the
      previous task. The results suggest that when participants choose to switch tasks,
      they prepare for that switch in anticipation of the stimulus, and the preparation
      is durable such that it cannot be readily undone. 

PMID- 24916774
TI  - New bonding modes of carbon and heavier group 14 atoms Si-Pb.
AB  - Recent theoretical studies are reviewed which show that the naked group 14 atoms
      E = C-Pb in the singlet (1)D state behave as bidentate Lewis acids that strongly
      bind two sigma donor ligands L in the donor-acceptor complexes L->E<-L.
      Tetrylones EL2 are divalent E(0) compounds which possess two lone pairs at E. The
      unique electronic structure of tetrylones (carbones, silylones, germylones,
      stannylones, plumbylones) clearly distinguishes them from tetrylenes ER2
      (carbenes, silylenes, germylenes, stannylenes, plumbylenes) which have electron
      sharing bonds R-E-R and only one lone pair at atom E. The different electronic
      structures of tetrylones and tetrylenes are revealed by charge- and energy
      decomposition analyses and they become obvious experimentally by a distinctively
      different chemical reactivity. The unusual structures and chemical behaviour of
      tetrylones EL2 can be understood in terms of the donor-acceptor interactions L
      >E<-L. Tetrylones are potential donor ligands in main group compounds and
      transition metal complexes which are experimentally not yet known. The review
      also introduces theoretical studies of transition metal complexes [TM]-E which
      carry naked tetrele atoms E = C-Sn as ligands. The bonding analyses suggest that
      the group-14 atoms bind in the (3)P reference state to the transition metal in a
      combination of sigma and pi? electron-sharing bonds TM-E and pi? backdonation TM
      >E. The unique bonding situation of the tetrele complexes [TM]-E makes them
      suitable ligands in adducts with Lewis acids. Theoretical studies of [TM]-E
      >W(CO)5 predict that such species may becomes synthesized. 

PMID- 24916775
TI  - [Serous ovarian tumors].
AB  - Because of different patterns of molecular changes, a dualistic model of serous
      tumors is now assumed with serous borderline tumors (SBT) and low-grade serous
      carcinomas (LGSC) on one side and high-grade serous carcinomas (HGSC) on the
      other. The clinical course and the type of treatment of SBT and LGSC depend
      crucially on whether they are associated with extraovarian manifestations. So
      called invasive implants of SBT correspond morphologically to LGSC. The MD
      Anderson grading system has become established for the distinction between LGSC
      and HGSC, HGSC shows a wide range of growth patterns, including a transitional
      epithelial-like type. Carcinosarcomas can be interpreted as HGSC variants.
      Considering the new theory that all serous neoplasms of the ovary, peritoneum and
      fallopian tubes are derived from the tubal fimbria, the term "ovarian carcinoma"
      seems no longer appropriate. 

PMID- 24916776
TI  - Human induced pluripotent stem cells improve recovery in stroke-injured aged
      rats.
AB  - PURPOSE: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons
      after implantation into the stroke-injured adult rodent brain. How the aged brain
      responds to grafted iPSCs is unknown. We determined survival and differentiation
      of grafted human fibroblast-derived iPSCs and their ability to improve recovery
      in aged rats after stroke. METHODS: Twenty-four months old rats were subjected to
      30 min distal middle cerebral artery occlusion causing neocortical damage. After
      48 h, animals were transplanted intracortically with human iPSC-derived long-term
      neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke
      and were vehicle-injected. RESULTS: Cell-grafted animals performed better than
      vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell
      proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to
      49.2% of that of implanted cells. Transplanted cells expressed markers of
      neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less
      activated microglia/macrophages in injured cortex and neuronal loss was
      mitigated. CONCLUSIONS: Our study provides the first evidence that grafted human
      iPSCs survive, differentiate to neurons and ameliorate functional deficits in
      stroke-injured aged brain.

PMID- 24916777
TI  - A comparative study of the metabolic profile, insulin sensitivity and
      inflammatory response between organically and conventionally managed dairy cattle
      during the periparturient period.
AB  - The number of organically managed cattle (OMC) within the European Union has
      increased tremendously in the last decade. However, there are still some concerns
      about animals under this farming system meeting their dietary requirements for
      milk production. The aim of this study was to compare the metabolic adaptations
      to the onset of lactation in three different herds, one conventional and two
      organic ones. Twenty-two conventionally managed cattle (CMC) and 20 from each
      organic farm were sampled throughout the periparturient period. These samplings
      were grouped into four different stages: (i) far-off dry, (ii) close-up dry,
      (iii) fresh and (iv) peak of lactation and compared among them. In addition, the
      results of periparturient animals were also compared within each management type
      with a control group (animals between the 4th and 5th months of pregnancy).
      Metabolic profiles were used to assess the health status of the herds, along with
      the quantification of the acute phase proteins haptoglobin and serum amyloid A,
      insulin and the calculation of different surrogate indices of insulin
      sensitivity. Generalised linear mixed models with repeated measurements were used
      to study the effect of the stage, management type or their interaction on the
      serum variables studied. The prevalence of subclinical ketosis was higher in OMC,
      although they showed better insulin sensitivity, a lower degree of inflammation
      and less liver injury, without a higher risk of macromineral deficiencies.
      Therefore, attention should be paid on organic farms to the nutritional
      management of cows around the time of calving in order to prevent the harmful
      consequences of excessive negative energy balance. Moreover, it must be taken
      into account that most of the common practices used to treat this condition in
      CMC are not allowed on a systematic basis in OMC. 

PMID- 24916778
TI  - Brachytherapy for prostate cancer: feasible but oncological equivalence unproven.

PMID- 24916779
TI  - [Analysis of the introduction of a telemedicine program in the primary health
      care area of Ibiza and Formentera].

PMID- 24916781
TI  - Peripheral nerve tractography in soft tissue tumors: a preliminary 3-tesla
      diffusion tensor magnetic resonance imaging study.
AB  - INTRODUCTION: This diffusion tensor magnetic resonance imaging (DTI) study aimed
      to clarify the relationship of peripheral nerves and soft tissue tumors (STTs) in
      3D to optimize subsequent treatment. METHODS: Twenty-six consecutive STT patients
      (histologically malignant, n=10; intermediate, n=3; and benign, n=13) underwent 3
      Tesla MRI using an echoplanar DTI sequence. Deterministic tractography was
      performed. Fractional anisotropy (FA) values were measured within peritumoral and
      distant regions of interest. RESULTS: Tractography depicted the 3D course of the
      sciatic (n=12), femoral (n=2), tibial (n=7), fibular (n=2), median (n=1),
      musculocutaneous (n=1), and ulnar (n=1) nerves in a regular (n=8 of 18, 44.4%) or
      thinned (n=7 of 18, 38.9%) fashion. The lowest peritumoral FA values, abrupt
      thinning, and/or complete discontinuity of trajectories were found in 2 cases
      with histologically proven tumoral nerve infiltration. CONCLUSIONS: DTI clarifies
      the 3D topography between major peripheral nerves and STTs and may be helpful in
      the assessment of peripheral nerve infiltration by malignant tumors.

PMID- 24916782
TI  - Author's reply.

PMID- 24916780
TI  - Co-opting biology to deliver drugs.
AB  - The goal of drug delivery is to improve the safety and therapeutic efficacy of
      drugs. This review focuses on delivery platforms that are either derived from
      endogenous pathways, long-circulating biomolecules and cells or that piggyback
      onto long-circulating biomolecules and cells. The first class of such platforms
      is protein-based delivery systems--albumin, transferrin, and fusion to the Fc
      domain of antibodies--that have a long-circulation half-life and are designed to
      transport different molecules. The second class is lipid-based delivery systems
      lipoproteins and exosomes-that are naturally occurring circulating lipid
      particles. The third class is cell-based delivery systems--erythrocytes,
      macrophages, and platelets--that have evolved, for reasons central to their
      function, to exhibit a long life-time in the body. The last class is small
      molecule-based delivery systems that include folic acid. This article reviews the
      biology of these systems, their application in drug delivery, and the promises
      and limitations of these endogenous systems for drug delivery.

PMID- 24916783
TI  - Restoring Akt1 activity in outgrowth endothelial cells from South Asian men
      rescues vascular reparative potential.
AB  - Recent data suggest reduced indices of vascular repair in South Asian men, a
      group at increased risk of cardiovascular events. Outgrowth endothelial cells
      (OEC) represent an attractive tool to study vascular repair in humans and may
      offer potential in cell-based repair therapies. We aimed to define and manipulate
      potential mechanisms of impaired vascular repair in South Asian (SA) men. In
      vitro and in vivo assays of vascular repair and angiogenesis were performed using
      OEC derived from SA men and matched European controls, prior defining potentially
      causal molecular mechanisms. SA OEC exhibited impaired colony formation,
      migration, and in vitro angiogenesis, associated with decreased expression of the
      proangiogenic molecules Akt1 and endothelial nitric oxide synthase (eNOS).
      Transfusion of European OEC into immunodeficient mice after wire-induced femoral
      artery injury augmented re-endothelialization, in contrast with SA OEC and
      vehicle; SA OEC also failed to promote angiogenesis after induction of hind limb
      ischemia. Expression of constitutively active Akt1 (E17KAkt), but not green
      fluorescent protein control, in SA OEC increased in vitro angiogenesis, which was
      abrogated by a NOS antagonist. Moreover, E17KAkt expressing SA OEC promoted re
      endothelialization of wire-injured femoral arteries, and perfusion recovery of
      ischemic limbs, to a magnitude comparable with nonmanipulated European OEC.
      Silencing Akt1 in European OEC recapitulated the functional deficits noted in SA
      OEC. Reduced signaling via the Akt/eNOS axis is causally linked with impaired OEC
      mediated vascular repair in South Asian men. These data prove the principle of
      rescuing marked reparative dysfunction in OEC derived from these men.

PMID- 24916784
TI  - Vitamin E intake and the lung cancer risk among female nonsmokers: a report from
      the Shanghai Women's Health Study.
AB  - Vitamin E includes several tocopherol isoforms, which may reduce lung cancer
      risk, but past studies evaluating the association between vitamin E intake and
      lung cancer risk were inconsistent. We prospectively investigated the
      associations between tocopherol intake from diet and from supplements with lung
      cancer risk among 72,829 Chinese female nonsmokers aged 40-70 years and
      participating in the Shanghai Women's Health Study (SWHS). Dietary and supplement
      tocopherol exposure was assessed by a validated food-frequency questionnaire at
      baseline and reassessed for change in intake during follow-up. Cox proportional
      hazards models with time-dependent covariates were used to calculate multivariate
      adjusted hazard ratios (HRs) and 95% confidence interval (CIs) for lung cancer.
      After 12.02 years of follow-up, 481 women were diagnosed with lung cancer. Total
      dietary tocopherol was inversely associated with lung cancer risk among women
      meeting dietary guidelines for adequate intake (AI) of tocopherol (14 mg/day or
      more: HR: 0.78; 95% CI 0.60-0.99; compared with the category less than AI). The
      protective association between dietary tocopherol intake and lung cancer was
      restricted to women exposed to side-stream smoke in the home and workplace [HR =
      0.53 (0.29-0.97), p-trend = 0.04]. In contrast, vitamin E supplement use was
      associated with increased lung cancer risk (HR: 1.33; 95% CI: 1.01-1.73), more so
      for lung adenocarcinoma risk (HR: 1.79; 95% CI: 1.23-2.60). In summary, dietary
      tocopherol intake may reduce the risk of lung cancer among female nonsmokers;
      however, supplements may increase lung adenocarcinoma risk and requires further
      investigation. 

PMID- 24916785
TI  - Relapse of acute megakaryocytic leukemia as hepatic myeloid sarcoma after
      allogeneic haploidentical hematopoietic stem cell transplantation.

PMID- 24916786
TI  - A group-randomized trial of shared decision making for non-steroidal anti
      inflammatory drug risk awareness: primary results and lessons learned.
AB  - RATIONALE, AIMS AND OBJECTIVES: Frequent use and serious adverse effects related
      to non-steroidal anti-inflammatory drugs (NSAIDs) underscore the need to raise
      patient awareness about potential risks. Partial success of patient- or provider
      based interventions has recently led to interest in combined approaches focusing
      on both patient and physician. This research tested a shared decision-making
      intervention for increasing patient-reported awareness of NSAID risk. METHODS: A
      group randomized trial was performed in Alabama from 2005 to 2007. Intervention
      group doctor practices received continuing medical education (CME) about NSAIDs
      and patient activation tools promoting risk assessment and communication during
      visits. Comparison group doctor practices received only CME. Cross-sectional data
      were collected before and after the intervention. Generalized linear latent and
      mixed models with logistic link tested relationships among the intervention,
      study phase, intervention by study phase interaction and patient-reported
      awareness of risks with either prescription or over-the-counter (OTC) NSAIDs.
      RESULTS: Three hundred and forty-seven patients at baseline and 355 patients at
      follow-up participated in this study. The intervention [adjusted odds ratio
      (AOR)=0.74, P=0.248], follow-up study phase (AOR=1.31, P=0.300) and intervention
      by study phase interaction (AOR=0.98, P=0.942) were not significantly associated
      with patient-reported awareness of any prescription NSAID risk. Follow-up study
      phase was associated with increased odds of reporting any OTC NSAID risk
      awareness (AOR=2.99, P<0.001), but the patient activation intervention and
      intervention by study phase interaction were not significantly associated with
      patient-reported awareness of any OTC NSAID risk (AOR=0.98, P=0.929; AOR=0.87,
      P=0.693, respectively). CONCLUSIONS: Our point-of-care intervention encouraging
      shared decision making did not increase NSAID risk awareness.

PMID- 24916787
TI  - Difference in immune response in vaccinated and unvaccinated Swedish individuals
      after the 2009 influenza pandemic.
AB  - BACKGROUND: Previous exposures to flu and subsequent immune responses may impact
      on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection
      with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative
      differences in humoral and cellular immune responses associated with the flu
      vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not
      yet been described in detail. We designed a longitudinal study to examine
      influenza- (flu-) specific immune responses and the association between pre
      existing flu responses, symptoms of influenza-like illness (ILI), impact of
      pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040
      individuals in Sweden in 2009-2010. METHODS: Cellular flu-specific immune
      responses were assessed by whole-blood antigen stimulation assay, and humoral
      responses by a single radial hemolysis test. RESULTS: Previous seasonal flu
      vaccination was associated with significantly lower flu-specific IFN-gamma
      responses (using a whole-blood assay) at study entry. Pandemic flu vaccination
      induced long-lived T-cell responses (measured by IFN-gamma production) to
      influenza A strains, influenza B strains, and the matrix (M1) antigen. In
      contrast, individuals with pandemic flu infection (PCR positive) exhibited
      increased flu-specific T-cell responses shortly after onset of ILI symptoms but
      the immune response decreased after the flu season (spring 2010). We identified
      non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN
      gamma production profile similar to pandemic-flu infected participants,
      suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong
      and long-lived flu-M1 specific immune responses, defined by IFN-gamma production,
      in individuals after vaccination suggest that M1-responses may contribute to
      protective cellular immune responses. Silent flu infections appeared to be
      frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and
      quantitatively different humoral and cellular immune responses as compared to
      infection with the 2009 H1N1 pandemic H1N1 influenza strain.

PMID- 24916789
TI  - Obesity and psychosocial impairment: mediating roles of health status,
      weight/shape concerns and binge eating in a community sample of women and men.
AB  - OBJECTIVES: We examined the relative importance of physical health status,
      weight/shape concerns and binge eating as mediators of the association between
      obesity and psychosocial impairment in a community sample of women and men.
      METHODS: Self-report measures of eating disorder features, perceived physical
      health and psychosocial functioning were completed by a general population sample
      of women and men classified as obese or non-obese (women: obese=276, non
      obese=1220; men: obese=169, non-obese=769). Moderated mediation analysis was used
      to assess the relative importance of each of the putative mediators in accounting
      for observed associations between obesity and each outcome measure and possible
      moderation of these effects by sex. RESULTS: Weight/shape concerns and physical
      health were equally strong mediators of the association between obesity and
      psychosocial impairment. This was the case for both men and women and for each of
      three measures of psychosocial functioning-general psychological distress, life
      satisfaction and social support-employed. The effects of binge eating were modest
      and reached statistical significance only for the life satisfaction measure in
      men. CONCLUSIONS: A greater focus on body acceptance may be indicated in obesity
      prevention and weight-management programs.

PMID- 24916790
TI  - The relationship of angiogenic factors to maternal and neonatal manifestations of
      early-onset and late-onset preeclampsia.
AB  - OBJECTIVE: An imbalance between angiogenic and antiangiogenic factors has been
      implicated in the pathogenesis and severity of preeclampsia. In this study, we
      evaluated serum levels of an angiogenic factor and an antiangiogenic factor -
      placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1),
      respectively - in pregnant women with preeclampsia, as well as evaluating the
      impact of those factors on maternal and fetal outcomes. METHOD: We studied 44
      pregnant women diagnosed with preeclampsia and admitted to an intensive care unit
      (ICU). The preeclampsia was classified (by weeks of gestation at delivery) as
      early-onset (<34 weeks) or late-onset (>=34 weeks). We analyzed serum PlGF and
      sFlt-1, as well as urinary PlGF at admission to the ICU. RESULTS: In the early
      onset preeclampsia group, the sFlt-1/PlGF ratio was higher, as was serum sFlt-1,
      whereas serum PlGF was lower. Serum sFlt-1 and the sFlt-1/PlGF ratio correlated
      positively with proteinuria and length of maternal hospital stay and correlated
      negatively with birth weight. The sFlt-1/PlGF ratio correlated positively with
      length of newborn stay in the neonatal ICU. CONCLUSION: Angiogenic imbalance is
      more pronounced in patients with early-onset preeclampsia and correlates with
      worse clinical outcomes, especially for the neonates.

PMID- 24916788
TI  - Circulating irisin levels and coronary heart disease: association with future
      acute coronary syndrome and major adverse cardiovascular events.
AB  - INTRODUCTION: Irisin is a newly discovered myokine, associated with 'browning' of
      the white adipose tissue, obesity, insulin resistance and metabolic syndrome. The
      purpose of this study is to evaluate circulating irisin as a predictor of acute
      coronary syndromes (ACSs) and major adverse cardiovascular events (MACE).
      METHODS: Sub-study 1: a case-control study, nested within the Veteran's Affairs
      Normative Ageing Study, evaluating circulating irisin levels in 88 ACS cases and
      158 age- and sampling year-matched controls, as a predictor of ACS. Sub-study 2:
      a prospective cohort study, where 103 participants with established coronary
      artery disease were stratified by circulating irisin levels at the time they
      received percutaneous coronary interventions (PCIs) and were followed for the
      development of MACE. RESULTS: Study 1: there was no association between irisin
      levels and ACS in otherwise healthy individuals (odds ratio: 1.00 95% confidence
      interval: (0.99-1.00)). Study 2: the incidence of MACE was significantly lower in
      the first irisin tertile compared with the second and third (incidence rate 0 vs
      0.92 (0.51-1.61) vs 0.57 (0.28-1.14) events per 1000 person-days; P < 0.01). This
      was primarily driven by the lower incidence of unstable angina (incidence rate 0
      vs 0.61 (0.31-1.22) vs 0.43 (0.19-0.96) per 1000 person-days; P = 0.01).
      CONCLUSION: This is the first study to date that demonstrates that, although
      circulating irisin levels do not predict the development of ACS in healthy
      individuals, increased irisin levels are associated with the development of MACE
      in patients with established coronary artery disease after PCI.

PMID- 24916791
TI  - Mutual interaction between iron homeostasis and obesity pathogenesis.
AB  - Obesity is identified as an important medical problem. One of the pathologic
      conditions observed in obesity is systemic iron deficiency and hypoferremia.
      Along with a large number of studies indicating disturbed iron homeostasis in
      obesity, recent data indicate a cause-effect relationship between iron status and
      obesity-related pathologies. The primary objective of the article is to consider
      two aspects of the iron-obesity interplay: (1) the mechanisms leading to impaired
      iron balance, and (2) the pathways of iron participation in obesity-related
      pathogenesis. While considering disturbance of iron homeostasis in obesity, a
      number of potential mechanisms of hypoferremia are proposed. At the same time,
      the inflammation of obesity and obesity-related hepcidin and lipocalin 2
      hyperproduction seem to be the most probable reasons of obesity-related
      hypoferremia. Oversecretion of these proteins leads to iron sequestration in
      reticuloendothelial system cells. The latter also leads to increased adipose
      tissue iron content, thus producing preconditions for adverse effects of local
      iron overload. Being a redox-active metal, iron is capable of inducing oxidative
      stress as well as endoplasmic reticulum stress, inflammation and adipose tissue
      endocrine dysfunction. Iron-mediated mechanisms of toxicity may influence aspects
      of obesity pathogenesis possibly even leading to obesity aggravation. Thus, a
      mutual interaction between disturbance in iron homeostasis and obesity
      pathogenesis is proposed. All sides of this interaction should be considered to
      design new therapeutic approaches to the treatment of disturbed iron homeostasis
      in obesity. 

PMID- 24916792
TI  - Pro-inflammatory effects of metals in persons and animals exposed to tobacco
      smoke.
AB  - Metals present in tobacco smoke have the ability to cause a pro
      oxidant/antioxidant imbalance through the direct generation of free radicals in
      accordance with the Fenton or Haber-Weiss reaction and redox properties. Metals
      can also interact with antioxidant enzymes (superoxide dismutase, catalase,
      glutathione peroxidase) and small molecular antioxidants (glutathione) through
      binding to SH groups or by replacement of metals ions in the catalytic center of
      enzymes. Excessive free radicals production can induce an inflammatory response.
      The aim of this study was to review the information on the induction of
      inflammation by metals present in tobacco smoke such as lead (Pb), cadmium (Cd),
      arsenic (As), aluminum (Al), nickel (Ni) and mercury (Hg). In cellular immune
      response, it was demonstrated that radicals induced by metals can disrupt the
      transcription signaling pathway mediated by the mitogen-activated protein kinase
      (induced by Pb), NLRP3-ASC-caspase 1 (induced by Ni), tyrosine kinase Src
      (induced by As) and the nuclear factor kappaB (induced by Pb, Ni, Hg). The result
      of this is a gene transcription for early inflammatory cytokines, such as
      Interleukine 1beta, Interleukine 6, and Tumor necrosis factor alpha). These
      cytokines can cause leukocytes recruitment and secretions of other pro
      inflammatory cytokines and chemokines, which intensifies the inflammatory
      response. Some metals, such as cadmium (Cd), can activate an inflammatory
      response through tissue damage induction mediated by free radicals, which also
      results in leukocytes recruitment and cytokines secretions. Inflammation
      generated by metals can be reduced by metallothionein, which has the ability to
      scavenge free radicals and bind toxic metals through the release of Zn and
      oxidation of SH groups. 

PMID- 24916793
TI  - Variance components of short-term biomarkers of manganese exposure in an
      inception cohort of welding trainees.
AB  - Various biomarkers of exposure have been explored as a way to quantitatively
      estimate an internal dose of manganese (Mn) exposure, but given the tight
      regulation of Mn in the body, inter-individual variability in baseline Mn levels,
      and variability in timing between exposure and uptake into various biological
      tissues, identification of a valuable and useful biomarker for Mn exposure has
      been elusive. Thus, a mixed model estimating variance components using restricted
      maximum likelihood was used to assess the within- and between-subject variance
      components in whole blood, plasma, and urine (MnB, MnP, and MnU, respectively) in
      a group of nine newly-exposed apprentice welders, on whom baseline and subsequent
      longitudinal samples were taken over a three month period. In MnB, the majority
      of variance was found to be between subjects (94%), while in MnP and MnU the
      majority of variance was found to be within subjects (79% and 99%, respectively),
      even when controlling for timing of sample. While blood seemed to exhibit a
      homeostatic control of Mn, plasma and urine, with the majority of the variance
      within subjects, did not. Results presented here demonstrate the importance of
      repeat measure or longitudinal study designs when assessing biomarkers of Mn, and
      the spurious associations that could result from cross-sectional analyses. 

PMID- 24916794
TI  - Immunosuppression and oxidative stress induced by subchronic exposure to
      carbosulfan in rat spleen: immunomodulatory and antioxidant role of N
      acetylcysteine.
AB  - The present study was designed to determine the immunosuppressive effects of
      carbosulfan (CB) and their relationship with an increased formation of reactive
      oxygen species in rat. Further, we aimed to evaluate the protective effects of N
      acetyl-cysteine (NAC) against immunopathological changes induced by CB.
      Carbosulfan (25 mg/kg) and NAC (2 g/l) were given daily to rats during 30 days,
      via oral gavage and drinking water, respectively. Cell-mediated immune function,
      cytokines production, biomarkers of cell redox state maintenance, lipid
      peroxidation and the activities of antioxidant enzymes were measured in the
      spleen. Our data showed an increase in WBC percent (28.42%), a reduction in
      spleen CD8 T-lymphocytes (-85.63%) and a decrease in immunosuppressive cytokines
      production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2
      type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a
      significant decrease in reduced glutathione (-71.68%) and total thiols (-39.81%)
      levels were observed in treated rats. Conversely, malondialdehyde level in spleen
      was increased (-42.3%), while glutathione-S-transferase, glutathione peroxidase,
      superoxide dismutase and catalase activities were depleted. Our results suggest
      that subchronic CB administration affects cellular enzyme and non-enzyme-mediated
      antioxidant defense systems and promotes immunotoxicity in rat. On the other
      hand, our data showed protective effects of NAC. Indeed, there was a recovery of
      oxidative stress markers and cytokines production. The use of NAC, in our study,
      as a therapeutic agent showed interesting results against CB toxicity.

PMID- 24916795
TI  - Liquid chromatography high-resolution TOF analysis: investigation of MSE for
      broad-spectrum drug screening.
AB  - BACKGROUND: High-resolution mass spectrometry (HRMS) has the potential to
      supplement other drug screening platforms used in toxicology laboratories. HRMS
      offers high analytical specificity, which can be further enhanced by
      incorporating a fragment ion for each analyte. The ability to obtain precursor
      ions and fragment ions using elevated collision energies (MS(E)) can help improve
      the specificity of HRMS methods. METHODS: We developed a broad-spectrum screening
      method on an ultraperformance liquid chromatography TOF mass spectrometer (UPLC
      TOF-MS) using the MS(E) mode. A diverse set of patient samples were subjected to
      a simple dilute, hydrolyze, and shoot protocol and analyzed in a blind manner.
      Data were processed with 3 sets of criteria with increasing stringency, and the
      results were compared with the reference laboratory results. RESULTS: A
      combination of retention time match (+/-0.2 min), a protonated analyte, and
      fragment ion mass accuracy of +/-5 ppm produced zero false-positive results.
      Using these criteria, we confirmed 92% (253/275) of true positives. The positive
      confirmation rate increased to 98% (270/275) when the requirement for a fragment
      ion was dropped, but also produced 53 false positives. A total of 136 additional
      positive drug findings not identified by the reference methods were identified
      with the UPLC-TOF-MS. CONCLUSIONS: MS(E) provides a unique way to incorporate
      fragment ion information without the need of precursor ion selection. A primary
      limitation of requiring a fragment ion for positive identification was that
      certain drug classes required high-energy collisions, which formed many fragment
      ions of low abundance that were not readily detected.

PMID- 24916796
TI  - Synthesis of large-pore mesostructured cellular foam silica spheres for the
      adsorption of biomolecules.
AB  - Mesostructured cellular foam (MCF) silica spheres with different textual
      parameters were synthesized using a triblock copolymer as a template. The effects
      of acid concentration and aging time on the window size and morphology were
      discussed. Besides, the adsorption performances of lysozyme and bovine serum
      albumin on the blank MCF with different window size and aminopropyl-modified MCFs
      were studied. The adsorption capacity and rates were shown to be dependent on the
      window size and surface chemical properties of the adsorbents. In particular, the
      MCF with window size of 15.2 nm showed fast adsorption for lysozyme with an
      adsorption capacity of 500 mg/g in 10 min. Furthermore, it has been shown that
      MCF spheres are potential materials in the separation of biomolecules because of
      their chemical tunable surface and molecular sieve properties. 

PMID- 24916798
TI  - Effect of local chain deformability on the temperature-induced morphological
      transitions of polystyrene-b-poly(N-isopropylacrylamide) micelles in aqueous
      solution.
AB  - The effect of temperature on the micellar morphology of two polystyrene-b-poly(N
      isopropylacrylamide) (PS-b-PNIPAM) diblock copolymers in an aqueous solution was
      investigated by dynamic light scattering (DLS) and transmission electron
      microscopy (TEM). At 25  degrees C, a mixture of vesicles and spheres are
      observed for the micelles of PS65-b-PNIPAM108, while PS65-b-PNIPAM360 exhibits
      mixed cylindrical and spherical micellar morphology. Upon increasing the
      temperature, the micellar morphology becomes spherical for PS65-b-PNIPAM108 at 60
      degrees C and for PS65-b-PNIPAM360 at 40  degrees C. Such vesicle-to-sphere and
      cylinder-to-sphere transitions of micellar morphology are reversible when the
      micellar solutions are cooled back to 25  degrees C. However, these temperature
      induced morphological transitions of the PS-b-PNIPAM micelles are contrary to the
      theoretical prediction. Qualitative analysis of the free energy shows that
      vesicular or cylindrical micelles tend to form at higher temperatures if only the
      overall volume change of the PNIPAM block is considered. The contradiction
      between the experimental results and theoretical prediction is interpreted in
      terms of the local deformability of the PNIPAM chains. At elevated temperatures,
      the collapsed PNIPAM globules are less deformable and must occupy larger areas at
      the micellar interface, although the overall volume is smaller at higher
      temperatures. This will lead to a larger repulsion between the PNIPAM globules
      and a remarkable increase in the free energy of the corona; thus, the formation
      of vesicles or cylinders at higher temperatures is prohibited. 

PMID- 24916797
TI  - Membrane deformation and scission by the HSV-1 nuclear egress complex.
AB  - The nuclear egress complex (NEC) of herpesviruses such as HSV-1 is essential for
      the exit of nascent capsids from the cell nucleus. The NEC drives nuclear
      envelope vesiculation in cells, but the precise budding mechanism and the
      potential involvement of cellular proteins are unclear. Here we report that HSV-1
      NEC alone is sufficient for membrane budding in vitro and thus represents a
      complete membrane deformation and scission machinery. It forms ordered coats on
      the inner surface of the budded vesicles, suggesting that it mediates scission by
      scaffolding the membrane bud and constricting the neck to the point of scission.
      The inward topology of NEC-mediated budding in vitro resembles capsid budding
      into the inner nuclear membrane during HSV-1 infection and nuclear envelope
      vesiculation in NEC-transfected cells. We propose that the NEC functions as
      minimal virus-encoded membrane-budding machinery during nuclear egress and does
      not require additional cellular factors. 

PMID- 24916799
TI  - Pattern of respiratory diseases in children presenting to the paediatric
      emergency unit of the University of Nigeria Teaching Hospital, Enugu: a case
      series report.
AB  - BACKGROUND: Respiratory diseases are one of the causes of childhood morbidity and
      mortality as well as hospitalization globally. The patterns of different
      respiratory illnesses in several parts of the world have been reported but there
      are few on the combined burden of the diseases. Determination of the burden of
      respiratory diseases as a group will help ascertain their collective impact on
      the health systems in order to develop intervention measures. METHODS: Data from
      case notes of children with respiratory diseases admitted to the University of
      Nigeria Teaching Hospital Enugu, Nigeria over a six year period were extracted.
      Age, gender, admission rates, types of respiratory illness, duration of
      admission, season of presentation and outcome were analysed. Descriptive and
      inferential (Chi square) statistics were used to describe the various disease
      types and ascertain association of the disease outcome, seasonal pattern with the
      types of diseases. RESULTS: Of the total of 8974 children admissions, 2214
      (24.7%) were due to respiratory diseases. The mean age of all the children with
      respiratory diseases was 3.3 years (SD 3.9). Communicable diseases were the
      common cause of admission cases throughout the seasons, p < 0.001. The highest
      admission rates were for pneumonia, (34.0%), acute bronchial asthma, (27.7%) and
      rhinosinusitis (14.6%) p < 0.001. The frequency of respiratory disease decreases
      with age and children less than five years of age and of low socio-economic
      status were commonly affected, p=0.01. The median duration of hospital stay was
      two days [range 1 to 8 days], children less than five years old and those of low
      socio-economic status, spent more than four days (p=0.01 and p < 0.001
      respectively). The all-cause mortality was 0.5% (11/2214) of which 81.8% (9/11)
      was due to pneumonia. CONCLUSIONS: Respiratory diseases constitute a significant
      burden of childhood illnesses in our centre. Efforts are required to reduce the
      impact as part of the steps towards the achievement of the Millennium Development
      Goals.

PMID- 24916800
TI  - Effect of swirling desolvation gas flow in an atmospheric pressure ion source.
AB  - A numerical study is performed to examine the effect of introducing a swirling
      desolvation gas flow on the flow transport characteristics in an electrospray and
      an atmospheric pressure chemical ionization (APCI) system. An ion source having
      three coaxial tubes is considered: (1) an inner capillary tube to inject the
      liquid sample, (2) a center coaxial tube to provide a room temperature gas flow
      to nebulize the liquid, referred to as the nebulizing gas flow, and (3) an outer
      coaxial tube having a converging exit to supply a high temperature gas for
      droplet desolvation, referred to as the desolvation gas flow. The results show
      that a swirling desolvation gas flow reduces the dispersion of the nebulizing gas
      and suppresses turbulent diffusion. The effect of swirling desolvation flow on
      the trajectory of a range of droplet sizes emitted from a source is also
      considered. 

PMID- 24916801
TI  - Effects of formulation and process factors on the crystal structure of freeze
      dried Myo-inositol.
AB  - The objective of this study was to elucidate effects of formulation and process
      variables on the physical forms of freeze-dried myo-inositol. Physical properties
      of myo-inositol in frozen solutions, freeze-dried solids, and cooled heat-melt
      solids were characterized by powder X-ray diffraction (PXRD), thermal analysis
      (differential scanning calorimetry [DSC] and thermogravimetric), and simultaneous
      PXRD-DSC analysis. Cooling of heat-melt myo-inositol produced two forms of
      metastable anhydrate crystals that change to stable form (melting point 225 
      degrees C-228  degrees C) with transition exotherms at around 123  degrees C and
      181  degrees C, respectively. Freeze-drying of single-solute aqueous myo-inositol
      solutions after rapid cooling induced crystallization of myo-inositol as
      metastable anhydrate (transition at 80  degrees C-125  degrees C) during
      secondary drying segment. Contrarily, postfreeze heat treatment (i.e., annealing)
      induced crystallization of myo-inositol dihydrate. Removal of the crystallization
      water during the secondary drying produced the stable-form myo-inositol anhydrate
      crystal. Shelf-ramp slow cooling of myo-inositol solutions resulted in the stable
      and metastable anhydrous crystal solids depending on the solute concentrations
      and the solution volumes. Colyophilization with phosphate buffer retained myo
      inositol in the amorphous state. Crystallization in different process segments
      varies crystal form of freeze-dried myo-inositol solids.

PMID- 24916802
TI  - Cloning and expression characteristics of the notch-associated gene
      BmE(spl)mgamma from silkworm, Bombyx mori.
AB  - The E(spl)mgamma gene in Drosophila is a regulatory target gene downstream of the
      Notch pathway. BmE(spl)mgamma (Bombyx mori, E(spl)mgamma) is an ortholog of the
      Drosophila E(spl)mgamma gene, and the gene encodes a protein with 248 amino acid
      residues. This gene was cloned and overexpressed in Escherichia coli BL21(DE3).
      The recombinant protein was purified and subsequently used to generate a rabbit
      polyclonal antibody. Western blotting analyses showed that BmE(spl)mgamma
      expression is high in pupa and egg, and low in larva and moth. In the fifth
      instar larva, the protein levels are high in head, epidermis, sexual gland,
      trachea, and the fatbody and low in the Malpighian tubule, hemolymph, gut, and
      silk gland. The further immunohistochemical analyses also showed higher
      BmE(spl)mgamma expression in the head of fifth instar larva and pupa. Of the four
      moth parts studied, the thorax had the highest expression level. Thus,
      BmE(spl)mgamma might be associated with neurogenesis in silkworm. Furthermore,
      DAPT (a gamma-secretase inhibitor and an indirect inhibitor of Notch) blocking
      experiments showed that higher concentrations of the blocking agent and a longer
      processing time reduce the transcription levels of the BmE(spl)mgamma gene,
      demonstrating that the silkworm BmE(spl)mgamma gene is associated with the Notch
      signal pathway. These findings suggest that the function of BmE(spl)mgamma may be
      similar to that of its Drosophila homolog. 

PMID- 24916803
TI  - Morphological control of conductive polymers utilized electrolysis polymerization
      technique: trial of fabricating biocircuit.
AB  - Conductive polymers are a strong contender for making electronic circuits. The
      growth pattern in conductive polymer synthesis by the electrolysis polymerization
      method was examined. The growth pattern is deeply related to the coupling
      reaction of the radical cation and the deprotonation reaction following it and
      changes suddenly depending on the kind and concentration of the supporting
      electrolyte and the solvent used. That is, when the electrophilic substitution
      coupling reaction becomes predominant, the three-dimensional growth form is
      observed, and when the radical coupling reaction becomes predominant, the two
      dimensional growth morphology is observed. In addition, the growth pattern can be
      comparatively easily controlled by changing the value of the polymerization
      constant current, and it is considered that the indicator and development for
      biocircuit research with neuron-type devices made of conjugated polymers was
      obtained. 

PMID- 24916804
TI  - Graphene oxide-based biosensor for food toxin detection.
AB  - We report results of the studies relating to the fabrication of a highly
      sensitive label free biosensor based on graphene oxide (GO) platform for the
      detection of aflatoxin B1 (AFB1) which is most toxic and predominant food toxin,
      using electrochemical impedance spectroscopy. The structural and optical
      characterization of GO/Au and anti-AFB1/GO/Au has been done by electron
      microscopy, Raman, X-ray diffraction (XRD), UV-vis and electrochemical impedance
      spectroscopy (EIS). The impedimetric sensing response of immunoelectrode as a
      function of AFB1 concentration reveals wider linear detection range (0.5-5
      ng/ml), high sensitivity (639 Omega ng(-1) ml), improved detection limit (0.23 ng
      ml(-1)) and good stability (5 weeks) for the label-free detection. Association
      constant (k a) for antigen-antibody interaction obtained as 0.46 ng ml(-1)
      indicates high affinity. 

PMID- 24916805
TI  - Kinetic modelling of thermal inactivation of a keratinase from Purpureocillium
      lilacinum LPSC # 876 and the influence of some additives on its thermal
      stability.
AB  - Thermal inactivation of a keratinase produced by Purpureocillium lilacinum LPSC
      #876 was kinetically investigated using several enzyme inactivation models at the
      temperature range of 50-65  degrees C. Among the models studied, the Weibull
      distribution was the best model that describes the residual activity of P.
      lilacinum keratinase after heat treatment over the selected temperatures. The
      stabilising effect of metal ions (Ca2+ or Mg2+, 5 mmol l(-1)) or polyols
      (propylene glycol and glycerol, 10% v/v) was investigated, showing that the
      presence of Ca2+ increases the enzyme stability significantly. Conforming to the
      increased Ca2+ concentration, thermal stability of the enzyme also increased,
      with 10 mM of Ca2+ being the concentration of metal in which the enzyme retained
      100% of its original activity after being incubated for 1 h at 55  degrees C. The
      effects of temperature on Weibull equation parameters and on the characteristics
      of the inactivation curves were evaluated. In the absence of any additives
      (control), the reliable time (t R) of the keratinase, analogous to D value,
      ranged from 484.16 to 63.67 min, while in the presence of Ca2+ the t R values
      ranged from 6,221 to 414.95 min at 50-65  degrees C. P. lilacinum keratinase is a
      potentially useful biocatalyst, and therefore, kinetic modelling of thermal
      inactivation addresses an important topic for its application in various
      industrial processes.

PMID- 24916806
TI  - Objective tongue inspection on 142 liver cancer patients with damp-heat syndrome.
AB  - OBJECTIVE: To establish the diagnosis evidence of objective tongue inspection for
      liver cancer (LC) patients with damp-heat syndrome (DHS) by dynamically observing
      their tongue figures using modern tongue image analytic apparatus, and to explore
      the effect of intervention on the tongue figures. METHODS: Tongue figures were
      collected from 142 LC patients with DHS by tongue image analytic apparatus. Red
      (R), green (G) and blue (B) values were analyzed. The r and g values were
      calculated requesting r=R/(R+G+B), g=G/(R+G+B), and b=1-r-g, and scored in
      combination with Chinese medical symptoms scale. The tongue figure and correlated
      scores were collected from 59 of them 3 days after transcatheter arterial
      chemoembolization intervention. RESULTS: The range of objective tongue inspection
      of LC patients with DHS was as follows: as for tongue fur, 0.360<r<0.402 and
      0.280<g<0.322; as for tongue proper, 0.404<r<0.470 and 0.243<g<0.301. The tongue
      figures and the average scores of quality of life, DHS, poor appetite, aggravated
      pain, decreased sleep quality and aggravated fever were obviously changed in the
      59 LC patients with DHS after intervention, showing statistical difference when
      compared with before intervention (P<0.05 or P<0.01). CONCLUSION: The range of
      objective tongue inspection of LC patients with DHS could be known by collecting
      and analyzing objective indicator of tongue figures, thus laying foundation for
      further studies with analysis of correlation between intervention and Chinese
      medicine based on tongue figures.

PMID- 24916807
TI  - Anti-inflammatory effects of Reduning Injection on lipopolysaccharide-induced
      acute lung injury of rats.
AB  - OBJECTIVE: To evaluate the protective effects of Reduning Injection (, RDN), a
      patent Chinese medicine, on lipopolysaccharide (LPS)-induced acute lung injury
      (ALI) in rats and its underlying mechanisms of action. METHODS: Sixty male
      Sprague-Dawley rats were randomly divided into 6 groups, including normal
      control, model, dexamethasone (DEX, 5 mg/kg), RDN-H (720 mg/kg), RDN-M (360
      mg/kg) and RDN-L (180 mg/kg) groups, with 10 rats in each group. Rats were
      challenged with intravenous injection of LPS 1 h after intraperitoneal treatment
      with RDN or DEX. At 6 h after LPS challenge, lung tissues and bronchoalveolar
      lavage fluid (BALF) were collected, and the number of inflammatory cells was
      determined. The right lungs were collected for histopathologic examination,
      measurement of gene and protein expressions, superoxide dismutase (SOD) and
      myeloperoxidase (MPO) activities. RESULTS: In vivo pretreatment of RDN (360, 720
      mg/kg) significantly reduced the weight of wet to dry (W/D) ratio of lung,
      protein content in BALF, and led to remarkable attenuation of LPS-induced
      histopathological changes in the lungs. Meanwhile, RDN enormously decreased BALF
      total inflammatory cells, especially neutrophil and macrophage cell numbers.
      Moreover, RDN increased SOD activity, inhibited MPO activity, alleviated LPS
      induced tumor neurosis factor-alpha (TNF-alpha) and inducible nitric oxide
      synthase (iNOS) expression in lung tissues. Furthermore, RDN (720 mg/kg)
      efficiently weakened nuclear factorkappa B (NF-kappaB) gene and protein
      expression. CONCLUSION: Anti-inflammatory effects of RDN was demonstrated to be
      preventing pulmonary neutrophil infiltration, lowering MPO activity, TNF-alpha
      and iNOS gene expression by inhibiting NF-kappaB activity in LPS-induced ALI.

PMID- 24916808
TI  - Analysis of clinical evaluation of response to treatment of Parkinson's disease
      with integrated Chinese and Western medicine therapy.
AB  - OBJECTIVE: To analyze the clinical evaluation of Parkinson's disease (PD)
      patients receiving integrated Chinese and Western medicine therapy. METHODS: One
      hundred and twenty patients were enrolled and randomly allocated to a control
      group or treatment group. Patients in the two groups received placebo and Bushen
      Huoxue Granule (, BHG), respectively. Both groups received baseline levodopa and
      benserazide (Madopar). The effects of treatment were assessed monthly during the
      9-month treatment. Means of evaluation included Unified PD Rating Scale (UPDRS)
      scores (II and III), sleep scale score, 10 m turn back test (getting up time, 10
      m*2 times, and turning time), timing motor test (TMT)-left and TMT-right, which
      were treated as the dependent variables; and age, sex, duration of PD, Hoehn and
      Yahr (H-Y) stage and Madopar dosage of admitted PD patients were as the
      independent variables. Multiple linear regression was used to analyze these
      factors. RESULTS: H-Y stage significantly affected UPDRS II score, UPDRS III
      score, and getting up time (P<0.01). Madopar dosage and H-Y stage significantly
      affected the 10 m*2 times (P<0.05 or <0.01). Madopar dosage significantly
      affected the sleep scale score (P<0.05). There were also significant correlations
      between age and TMT-left or TMT-right (P<0.01), and duration of PD and TMT-right
      (P<0.05). CONCLUSIONS: The six assessed means of clinical evaluation (including
      UPDRS II and UPDRS III scores, sleep scale score, getting up time, 10 m*2 times,
      and turning time) are sensitive indexes in all PD patients. H-Y stage and Madopar
      dosage are the major factors influencing means of clinical assessment of PD
      treatment.

PMID- 24916809
TI  - Outpatient antibiotic prescribing in the United States: 2000 to 2010.
AB  - BACKGROUND: The use of antibiotics is the single most important driver in
      antibiotic resistance. Nevertheless, antibiotic overuse remains common. Decline
      in antibiotic prescribing in the United States coincided with the launch of
      national educational campaigns in the 1990s and other interventions, including
      the introduction of routine infant immunizations with the pneumococcal conjugate
      vaccine (PCV-7); however, it is unknown if these trends have been sustained
      through recent measurements. METHODS: We performed an analysis of nationally
      representative data from the Medical Expenditure Panel Surveys from 2000 to 2010.
      Trends in population-based prescribing were examined for overall antibiotics,
      broad-spectrum antibiotics, antibiotics for acute respiratory tract infections
      (ARTIs) and antibiotics prescribed during ARTI visits. Rates were reported for
      three age groups: children and adolescents (<18 years), adults (18 to 64 years),
      and older adults (>=65 years). RESULTS: An estimated 1.4 billion antibiotics were
      dispensed over the study period. Overall antibiotic prescribing decreased 18%
      (risk ratio (RR) 0.82, 95% confidence interval (95% CI) 0.72 to 0.94) among
      children and adolescents, remained unchanged for adults, and increased 30% (1.30,
      1.14 to 1.49) among older adults. Rates of broad-spectrum antibiotic
      prescriptions doubled from 2000 to 2010 (2.11, 1.81 to 2.47). Proportions of
      broad-spectrum antibiotic prescribing increased across all age groups: 79% (1.79,
      1.52 to 2.11) for children and adolescents, 143% (2.43, 2.07 to 2.86) for adults
      and 68% (1.68, 1.45 to 1.94) for older adults. ARTI antibiotic prescribing
      decreased 57% (0.43, 0.35 to 0.52) among children and adolescents and 38% (0.62,
      0.48 to 0.80) among adults; however, it remained unchanged among older adults.
      While the number of ARTI visits declined by 19%, patients with ARTI visits were
      more likely to receive an antibiotic (73% versus 64%; P <0.001) in 2010 than in
      2000. CONCLUSIONS: Antibiotic use has decreased among children and adolescents,
      but has increased for older adults. Broad-spectrum antibiotic prescribing
      continues to be on the rise. Public policy initiatives to promote the judicious
      use of antibiotics should continue and programs targeting older adults should be
      developed.

PMID- 24916810
TI  - MN typing discrepancies based on GYPA-B-A hybrid.
AB  - BACKGROUND AND OBJECTIVES: Gene conversion events between GYPA and GYPB or GYPA
      and GYPE are facilitated by the close chromosomal proximity and high degree of
      sequence homology and can lead to the formation of GP hybrid genes. Discrepant
      results between blood group genotyping and haemagglutination in 22 random blood
      donors induced molecular characterization. MATERIALS AND METHODS: Sequence
      analysis of GYPA exons 1-7 and GYPB exons 1-5 was performed for gDNA and cDNA.
      The linkage of the nucleotide alterations was defined by haplotype separation.
      RESULTS: DNA analysis demonstrated a normal GYPA haplotype (GYPA*N n = 20, GYPA*M
      n = 2) with an altered GP hybrid nucleotide sequence in trans. A GYPB homologue
      sequence of minimal 10-bp encompassing intron 1 and exon 2 was translated into
      GYPA, accounting for an amino acid substitution from arginine to glutamic acid at
      position 13 (38 C>A). Genomic DNA analysis demonstrated the cis-linkage of the
      hybrid nucleotide sequence with each GYPA(Ser20, Gly24) (n = 20) associated with
      the expression of M and GYPA(Leu20, Glu24) (n = 2) encoding the N phenotype. The
      serologic data indicate that the changes do not affect the expression of a normal
      M and N antigen. cDNA sequences confirmed the gDNA results and furthermore
      identified a heterozygous deletion of GYPB exon 2 in all probands. CONCLUSION:
      The results document a GYPA-B-A hybrid gene, probably produced via a single
      unequal homologous recombination event. A segmental transfer of GYPB seems most
      likely accounting for the allelic dropout.

PMID- 24916811
TI  - Chitosan-protein scaffolds loaded with lysostaphin as potential
      antistaphylococcal wound dressing materials.
AB  - AIMS: The development of technology for preparing chitosan-protein scaffolds
      loaded with lysostaphin, which potentially could be used as dressing for wound
      treatment and soft tissue infections caused by Staphylococcus aureus. METHODS AND
      RESULTS: The unique technology of chitosan solubilization using gaseous CO(2)
      instead of organic or inorganic acids was used for the incorporation of
      lysostaphin, the enzyme that exhibits bactericidal activity against
      staphylococci, within the structure of chitosan-protein sponges. The developed
      chitosan-protein scaffolds loaded with lysostaphin revealed high
      antistaphylococcal activity, which has been confirmed with a large (n = 143)
      collection of clinical (skin and wound infections) and animal (bovine mastitis)
      isolates of these bacteria, including MRSA. No change of bactericidal activity of
      the lyophilized materials has been observed during half-year storage at 4 degrees
      C. CONCLUSIONS: The developed materials are potential candidates for preparing
      biologically active, antistaphylococcal wound dressing materials. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Staphylococci belong to the most popular and most
      burdensome aetiological factors of wound and soft tissues infections. The
      developed chitosan-protein scaffolds loaded with lysostaphin could be a possible
      solution to problems associated with treatment of these infections.

PMID- 24916812
TI  - Perceived Control and Psychological Contract Breach as Explanations of the
      Relationships Between Job Insecurity, Job Strain and Coping Reactions: Towards a
      Theoretical Integration.
AB  - This study aims to further knowledge on the mechanisms through which job
      insecurity is related to negative outcomes. Based on appraisal theory, two
      explanations-perceived control and psychological contract breach-were
      theoretically integrated in a comprehensive model and simultaneously examined as
      mediators of the job insecurity-outcome relationship. Different categories of
      outcomes were considered, namely work-related (i.e. vigour and need for recovery)
      and general strain (i.e. mental and physical health complaints), as well as
      psychological (i.e. job satisfaction and organizational commitment) and
      behavioural coping reactions (i.e. self-rated performance and innovative work
      behaviour). The hypotheses were tested using data of a heterogeneous sample of
      2413 Flemish employees by means of both single and multiple mediator structural
      equation modelling analyses (bootstrapping method). Particularly, psychological
      contract breach accounted for the relationship between job insecurity and strain.
      Both perceived control and psychological contract breach mediated the
      relationships between job insecurity and psychological coping reactions, although
      the indirect effects were larger for psychological contract breach. Finally,
      perceived control was more important than psychological contract breach in
      mediating the relationships between job insecurity and behavioural coping
      reactions. This study meets previous calls for a theoretical integration
      regarding mediators of the job insecurity-outcome relationship.

PMID- 24916813
TI  - Cyclodextrin-templated porphyrin nanorings.
AB  - alpha- and beta-cyclodextrins have been used as scaffolds for the synthesis of
      six- and seven-legged templates by functionalizing every primary CH2OH with a 4
      pyridyl moiety. Although these templates are flexible, they are very effective
      for directing the synthesis of macrocyclic porphyrin oligomers consisting of six
      or seven porphyrin units. The transfer of chirality from the cyclodextrin
      templates to their nanoring hosts is evident from NMR and circular dichroism
      spectroscopy. Surprisingly, the mean effective molarity for binding the flexible
      alpha-cyclodextrin-based template within the six-porphyrin nanoring (74 M) is
      almost as high as for the previously studied rigid hexadentate template (180 M).
      The discovery that flexible templates are effective in this system, and the
      availability of a template with a prime number of binding sites, open up many
      possibilities for the template-directed synthesis of larger macrocycles.

PMID- 24916814
TI  - Predictive equations for the estimation of body size in seals and sea lions
      (Carnivora: Pinnipedia).
AB  - Body size plays an important role in pinniped ecology and life history. However,
      body size data is often absent for historical, archaeological, and fossil
      specimens. To estimate the body size of pinnipeds (seals, sea lions, and
      walruses) for today and the past, we used 14 commonly preserved cranial
      measurements to develop sets of single variable and multivariate predictive
      equations for pinniped body mass and total length. Principal components analysis
      (PCA) was used to test whether separate family specific regressions were more
      appropriate than single predictive equations for Pinnipedia. The influence of
      phylogeny was tested with phylogenetic independent contrasts (PIC). The accuracy
      of these regressions was then assessed using a combination of coefficient of
      determination, percent prediction error, and standard error of estimation. Three
      different methods of multivariate analysis were examined: bidirectional stepwise
      model selection using Akaike information criteria; all-subsets model selection
      using Bayesian information criteria (BIC); and partial least squares regression.
      The PCA showed clear discrimination between Otariidae (fur seals and sea lions)
      and Phocidae (earless seals) for the 14 measurements, indicating the need for
      family-specific regression equations. The PIC analysis found that phylogeny had a
      minor influence on relationship between morphological variables and body size.
      The regressions for total length were more accurate than those for body mass, and
      equations specific to Otariidae were more accurate than those for Phocidae. Of
      the three multivariate methods, the all-subsets approach required the fewest
      number of variables to estimate body size accurately. We then used the single
      variable predictive equations and the all-subsets approach to estimate the body
      size of two recently extinct pinniped taxa, the Caribbean monk seal (Monachus
      tropicalis) and the Japanese sea lion (Zalophus japonicus). Body size estimates
      using single variable regressions generally under or over-estimated body size;
      however, the all-subset regression produced body size estimates that were close
      to historically recorded body length for these two species. This indicates that
      the all-subset regression equations developed in this study can estimate body
      size accurately. 

PMID- 24916815
TI  - The BMJ's own patient journey.

PMID- 24916816
TI  - Editorial.

PMID- 24916817
TI  - Diet blues: Methodological problems in comparing non-pharmacological weight
      management programs for patients with schizophrenia.
AB  - Obesity is an evident problem in patients with schizophrenia because it involves
      serious risks of health and has major effects on morbidity and mortality.
      Compared with the general population the prevalence of obesity is significantly
      increased in people with schizophrenia. Since second-generation antipsychotics
      have been established, the problem has become even more prevalent. Causes and
      treatment of obesity are both very complex issues. This article analyzes weight
      management programs for people with schizophrenia in regard to scientific
      methodology like intervention criteria, target definition and study design. 

PMID- 24916818
TI  - A comparative study of the components of sleep quality in medical outpatients.
AB  - Background. Almost any medical illness that causes significant pain or discomfort
      may negatively affect the quality of sleep. Moreover sleep disorders may coexist
      with medical disorders in people of all ages. Measuring sleep dysfunction is an
      area of active research, but few studies examined subjective ratings of sleep
      quality in medical patients Method. A total of 250 medical patients with various
      somatic complaints who attended the ENT, internal, neurology, orthopaedics and
      urology clinics participated in this study. The patients completed the Pittsburgh
      Sleep Quality Index (PSQI) which measures the quality of sleep in seven major
      domains and helps discriminate between individuals who experience poor sleep
      versus individuals who sleep well. A score >=6 is considered as a significant
      sleep disturbance. Results. The PSQI score of the patients from all selected
      clinics were higher than the reported cut-off point (Mean = 8, SD = 3.42).
      Significant differences were found in sleep duration (component 3) and sleep
      disturbances (component 5) between clinics. Pain and worry were the major causes
      of sleep disturbances reported by the majority of the patients. Conclusion. Sleep
      disturbances in medically ill patients require careful evaluation for proper
      treatment that will alleviate the sleep problem without exacerbating concomitant
      illnesses. Essentially any condition that causes pain or discomfort may cause
      insomnia and must be considered in the overall treatment plan. 

PMID- 24916819
TI  - Clinical utility of Patient Health Questionnaire-9 (PHQ-9) in memory clinics.
AB  - Background. Both dementia and depression may produce complaints of memory
      impairment. Differential diagnosis may be difficult, but has practical
      implications regarding choice of appropriate treatment. Aim. To assess the
      clinical utility of the Patient Health Questionnaire-9 (PHQ-9), a validated
      instrument for measurement of depression severity, in differentiating patients
      with and without dementia, referred with complaints of memory impairment to
      dedicated memory clinics. Methods. Pragmatic prospective study of consecutive
      referrals (n=113) to two dementia clinics, diagnosed using standard clinical
      diagnostic criteria for dementia (DSM-IV) and also administered the PHQ-9.
      Results. PHQ-9 proved acceptable to patients, and was quick and easy to use.
      Using traditional parameters of diagnostic utility (sensitivity, specificity,
      positive predictive value, likelihood ratios), PHQ-9 performance was modest for
      the diagnosis of dementia. However, pragmatically PHQ-9 scores proved helpful in
      deciding which patients, both with and without dementia, required a trial of
      antidepressant medication. Conclusions. PHQ-9 proved useful as a brief screen for
      depression in patients attending dementia clinics with a complaint of memory
      impairment. 

PMID- 24916820
TI  - Effectiveness and tolerability of long-acting risperidone: A 9-month open-label
      extension of a 12-week switching study from oral antipsychotics.
AB  - Objectives. The aim of this non-randomized, single-arm, multi-center, 9-month
      extension study was to evaluate the maintained efficacy and tolerability of long
      acting risperidone injection when we switched to it from previous oral
      antipsychotics in symptomatically stable patients with schizophrenia or other
      psychotic disorders. Methods. A total of 98 patients who had completed a previous
      12-week acute phase study were included. Efficacy and tolerability were assessed
      with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression
      (CGI), Global Assessment of Functioning (GAF), and Extrapyramidal Symptom Rating
      Scale (ESRS). Results. The remission rate of 77.6% (76/98) at baseline and 57.1%
      (56/98) at the end of the study. Of patients who were in remission at baseline,
      65.8% (50/76) maintained their remission state until the end. The symptom
      worsening rate was relatively low (11.1%), and there was no aggravation in mean
      PANSS total and subscale scores. Spontaneous treatment-emergent adverse events
      (TEAE) were reported by 21 (21.4%) patients, and most commonly reported adverse
      events were extrapyramidal symptoms (N=6, 6.1%) and insomnia (N=4, 4.1%).
      Extrapyramidal symptoms were significantly improved. Conclusions. Switching to
      long-acting risperidone injection from oral antipsychotics was a safe and well
      tolerated strategy for maintaining clinical stability in symptomatically stable
      patients with schizophrenia. 

PMID- 24916821
TI  - Comparison of plasma levels between oral solution and fine granule dosage forms
      of risperidone.
AB  - Objective. In Japan, there are several clinical reports that risperidone (RIS)
      oral solution (OS) requires shorter time for tranquilization and induces fewer
      extrapyramidal symptoms (EPS) than other dosage forms; i.e. fine granules (FG).
      Our aim is to compare plasma levels of RIS, its active metabolite (9-OH-RIS), and
      their sum (active moiety; AM) between RIS-OS and RIS-FG in a multiple-dose
      regimen. Method. A 12-week cross-over study was conducted in nine patients with
      schizophrenia treated with 3 mg of RIS twice daily. The study period was divided
      into four terms, each term being 3 weeks. RIS-FG and RIS-OS were given in two
      alternate terms each. Blood samples were collected on the last day of each term
      just before and at 1 h after RIS treatment to measure plasma levels of RIS, 9-OH
      RIS, and prolactin. Result. Plasma levels of RIS, 9-OH-RIS, AM, and prolactin
      before treatment were significantly lower for RIS-OS than for RIS-FG, while no
      significant difference was observed between the two forms at 1 h after
      administration. Conclusion. In a multiple-dose regimen, RIS-OS treatment caused a
      larger diurnal fluctuation in plasma level of AM than RIS-FG. These variations
      may explain the differences in severity of EPS between the 2 forms. 

PMID- 24916822
TI  - Prospective evaluation of insomnia in prison using the Pittsburgh Sleep Quality
      Index: Which are the factors predicting insomnia?
AB  - Objectives. To measure the subjective sleep quality of prisoners complaining of
      insomnia and to compare it to the subjective sleep quality of prisoners who
      report "good sleep", in order to determine factors that predict insomnia and
      severity of insomnia. Participants and methods. PSQI and GHQ scores and patient
      history were obtained for 86 randomly chosen remanded prisoners complaining of
      insomnia and 61 randomly chosen prisoners who did not complain of insomnia.
      Results. PSQI total and component scores were significantly different between
      insomniac and not insomniac prisoners, except for C7 (daytime dysfunction). A
      history of sleeping problems before prison (odds ratio: 13.3), the subjective
      experience of having had stressful events during the past week (odds ratio: 8.5),
      being separated or divorced (odds ratio: 8.8), GHQ >10 (odds ratio: 8.8), a
      history of psychiatric problems (odds ratio: 8.3) and the consumption of opiates
      (odds ratio: 7.9), and to a lesser degree "no sports in prison" and stress
      related to judicial, familial and prison problems, were predictors of insomnia.
      We did not find any evidence in this study that work or consumption of caffeine
      in prison were factors that distinguished good sleepers from insomnia patients.
      Conclusions. Our study helps prison physicians to identify prisoners at risk for
      insomnia and to obtain some orientation for treatment decisions. Psychological
      support to reduce context related stress should be routinely offered to insomniac
      prisoners. 

PMID- 24916823
TI  - Psychosocial aspects of living-related donor renal transplantation: Quality of
      life and mood in recipients, donors and controls.
AB  - Due to the high frequency of living-related donor renal transplantation (LRDRT)
      in our country, we were concerned both about the recipient and the donor quality
      of life and psychological well-being. We investigated HRQL and mood in LRDRT
      recipients, donors, and controls using the Beck Depression Inventory, Beck
      Anxiety Inventory, and 36-item Short Form Health Survey. The recipient group
      consisted of 69 individuals who underwent renal transplantation between August
      2002 and June 2004. The donor group consisted of 35 and the control group 45
      healthy individuals. Multivariate analysis of variance and the post hoc (Tukey)
      test were used to assess and to analyze differences among and between the three
      groups. The depression scores of the recipients were higher than donors (P <
      0.05) but were similar to controls. The recipient scores indicated poorer
      physical functioning (P < 0.001), greater physical limitation on roles (P <
      0.001), and lower levels of general health (P < 0.01) compared to controls. The
      donor scores indicated higher vitality (P < 0.01), better social functioning (P <
      0.05) and greater mental health (P < 0.01) than controls. Poorer health and mood
      status among the recipient group might reflect the various negative impacts of
      chronic debilitating disease. It is therefore recommended to screen recipients
      regularly for clinically relevant HRQL impairments after transplantation. 

PMID- 24916824
TI  - What is the "mask" of depressed inpatients from the viewpoint of surgeons and
      internal medicine physicians?
AB  - Objective. Depressed inpatients are easily misrecognized by general hospital
      physicians. Therefore, our study aimed to examine the following issues: (1) how
      primary care doctors recognize depressed inpatients; (2) if there are any
      differences between internal medicine physicians and surgeons with regard to this
      recognition; (3) the factors associated with the accurate recognition of
      depression. Methods. Four hundred and twenty-five consecutive patients from
      internal medical or surgical wards who had been diagnosed with depression were
      enrolled in this study. The reasons for referral were recorded from the referral
      sheet. Accurate recognition of depression was defined as depressive disorder or
      depressed core symptoms, which were the reasons for referral. Results. The rate
      of correct recognition of depression was the same for both physicians and
      surgeons. Depressed inpatients from the internal medicine wards were referred
      more commonly for suicide problems and unexplained physical symptoms, while a
      greater number of depressed patients from the surgical wards were referred for
      insomnia, agitation/irritability, cognitive impairment, and past psychiatric
      history. Multiple physical comorbidities, depression treatment history, and
      depression of a higher severity were independent factors associated with accurate
      recognition. Conclusions. Postgraduate education is still needed with regarded to
      understanding depression. The educational content should be specific to the
      different specialties and the patient characteristics in different wards. 

PMID- 24916825
TI  - Repeated suicidal behaviour: Stressful life events and 5-HTTLPR genetic
      polymorphism.
AB  - Stressful life events and dysregulated mono-aminergic neurotransmission have been
      associated with suicidal behaviour. The aim of this investigation was to analyze
      suicidal behaviour in multiple attempters in relation to the stressful life
      events, and to the polymorphism of the serotonin transporter (SERT) gene.
      Multiple suicide attempters, admitted to the University Psychiatric Clinic, were
      interviewed for the number of previous suicide attempts and for the occurrence of
      stressful life events, recorded in a Life History Calendar. The patients were
      further genotyped for 5-HTTLPR polymorphism of SERT. The number of suicide
      attempts was found to be significantly correlated with the number of negative
      life events experienced during the 6 months preceding each suicide attempt. The
      L/L genotype was associated with a reduced number of multiple suicide attempts.
      These results should prompt future study with a larger number of subjects to
      further investigate the interaction of genetic and environmental factors in
      repeated suicidal behaviour. 

PMID- 24916826
TI  - A re-examination of childhood trauma and somatic preoccupation.
AB  - In this study, we assessed five types of childhood trauma (i.e., physical,
      sexual, and emotional abuses; the witnessing of violence; physical neglect) and
      their relationship to somatic preoccupation in adulthood. Using a cross-sectional
      sample of convenience, we surveyed 113 individuals who were being seen as
      outpatients in an internal medicine setting and seeking non-emergent medical
      care. With yes/no response options, we inquired about five types of childhood
      trauma (i.e., physical, sexual, and emotional abuses; the witnessing of violence;
      physical neglect) and measured somatic preoccupation with the Bradford Somatic
      Inventory, a self-report measure. In this study, both physical and emotional
      abuses demonstrated significant correlations with scores on the Bradford Somatic
      Inventory. These findings suggest that physical and emotional abuses in childhood
      may have some relationship with somatic preoccupation in adulthood. 

PMID- 24916827
TI  - Childhood trauma and self-harm behavior among chronic pain patients.
AB  - Associations between childhood trauma and self-harm behavior in adulthood have
      been explored in a variety of populations, but few studies have assessed multiple
      forms of childhood trauma as well as 22 self-harm behaviors, and none (that we
      are aware of) in a chronic pain population. In this study, we examined 5 types of
      childhood trauma (i.e., sexual, physical, and emotional abuses; physical neglect;
      witnessing of violence) and 22 self-harm behaviors in a sample of 117 chronic
      pain patients who were being evaluated by a pain management specialist in a
      private setting. All five forms of childhood trauma demonstrated statistically
      significant relationships with self-harm behavior in adulthood. We discuss the
      implications of these findings. 

PMID- 24916828
TI  - Adverse events of placebo-treated, drug-resistant, focal epileptic patients in
      randomized controlled trials: a systematic review.
AB  - Health-related quality of life of patients with epilepsy is heavily influenced by
      antiepileptic drug (AED) tolerability. However, an accepted method for precise
      assessment of AED-induced adverse events (AEs) has not yet been established.
      Assessment of tolerability and of the frequency of predefined AEs among drug
      resistant epilepsy patients through an analysis of placebo-treated patients from
      randomized controlled studies (RCTs) performed in patients with partial onset
      epilepsies (POS) and evaluation of factors which may influence the occurrence of
      AEs in these patients are the objectives of this study. We searched all double
      blind, placebo-controlled trials investigating any AED on adult patients with POS
      and extracted both for patients treated with placebo and for those treated with
      the active drug, number of patients, number of responders, number of patients
      withdrawing because of AEs, number of patients with AEs, and number of patients
      with 11 predefined AEs. We also explored the effect of multiple factors on AEs
      reporting. Seventy-nine RCTs were included in our study with 12,594 patients,
      6,793 of whom randomized to placebo. In placebo-treated patients, overall
      responder rate was 15.2 %, proportion of placebo-treated patients withdrawing
      because of AEs was 3.9 %, and proportion of patients with AE was 60.3 %. The four
      most frequently reported AEs were headache (12.4 %) somnolence (8.6 %), dizziness
      (8.2 %), and fatigue (7.9 %). Several factors were found to influence these
      outcomes. Several factors influence AEs' appearance in RCTs. Among the most
      important, we found the expectations of patients and doctors and their attitudes
      on the positive or negative effect of a drug. 

PMID- 24916829
TI  - Internal consistency of the University of Michigan RBD Questionnaire.

PMID- 24916830
TI  - Wilhelm Uhthoff (1853-1927).

PMID- 24916831
TI  - A case of amyotrophic lateral sclerosis with intermediate ATXN-1 CAG repeat
      expansion in a large family with spinocerebellar ataxia type 1.

PMID- 24916833
TI  - Evaluating different methods used in ethnobotanical and ecological studies to
      record plant biodiversity.
AB  - BACKGROUND: This study compares the efficiency of identifying the plants in an
      area of semi-arid Northeast Brazil by methods that a) access the local knowledge
      used in ethnobotanical studies using semi-structured interviews conducted within
      the entire community, an inventory interview conducted with two participants
      using the previously collected vegetation inventory, and a participatory workshop
      presenting exsiccates and photographs to 32 people and b) inventory the
      vegetation (phytosociology) in locations with different histories of disturbance
      using rectangular plots and quadrant points. METHODS: The proportion of species
      identified using each method was then compared with Cochran's Q test. We
      calculated the use value (UV) of each species using semi-structured interviews;
      this quantitative index was correlated against values of the vegetation's
      structural importance obtained from the sample plot method and point-centered
      quarter method applied in two areas with different historical usage. The analysis
      sought to correlate the relative importance of plants to the local community (use
      value-UV) with the ecological importance of the plants in the vegetation
      structure (importance value-IV; relative density-RD) by using different sampling
      methods to analyze the two areas. RESULTS: With regard to the methods used for
      accessing the local knowledge, a difference was observed among the ethnobotanical
      methods of surveying species (Q=13.37, df=2, p=0.0013): 44 species were
      identified in the inventory interview, 38 in the participatory workshop and 33 in
      the semi-structured interviews with the community. There was either no
      correlation between the UV, relative density (RD) and importance value (IV) of
      some species, or this correlation was negative. CONCLUSION: It was concluded that
      the inventory interview was the most efficient method for recording species and
      their uses, as it allowed more plants to be identified in their original
      environment. To optimize researchers' time in future studies, the use of the
      point-centered quarter method rather than the sample plot method is recommended.

PMID- 24916832
TI  - Age dependency of safety and outcome of endovascular therapy for acute stroke.
AB  - Elderly patients generally experience less favorable outcomes and higher
      mortality after acute stroke than younger patients. The aim of this study was to
      analyze the influence of age on outcome and safety after endovascular therapy in
      a large cohort of patients aged between 20 and 90 years. We prospectively
      acquired data of 1,000 stroke patients treated with endovascular therapy at a
      single center. Logistic regression analysis was performed to determine predictors
      of outcome and linear regression analysis to evaluate the association of age and
      outcome after 3 months. Younger age was an independent predictor of favorable
      outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate
      regression analysis. There was a linear relationship between age and outcome.
      Ever increase in 26 years of age was associated with an increase in the modified
      Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk
      factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral
      hemorrhage and did not influence recanalization success (p = 0.674). Advancing
      age was associated with a decline of favorable outcomes and survival after
      endovascular therapy. This decline was linear from age 20 to 90 years, but was
      not related to lower recanalization rates or higher bleeding risk in the elderly.
      The efficacy of endovascular stroke therapy seems to be preserved also in the
      elderly and other factors than efficacy of endovascular therapy such as decreased
      plasticity are likely to explain the worse outcome with advancing age.

PMID- 24916834
TI  - Responses of high-elevation herbaceous plant assemblages to low glacial CO2
      concentrations revealed by fossil marmot (Marmota) teeth.
AB  - Atmospheric CO2 cycles of the Quaternary likely imposed major constraints on the
      physiology and growth of C3 plants worldwide. However, the measured record of
      this remains both geographically and taxonomically sparse. We present the first
      reconstruction of physiological responses in a late Quaternary high-elevation
      herbaceous plant community from the Southern Rocky Mountains, USA. We used a
      novel proxy-fossilized tooth enamel of yellow-bellied marmots (Marmota
      flaviventris)-which we developed using detailed isotopic analysis of modern
      individuals. Calculated C isotopic discrimination (Delta) of alpine plants was
      nearly 2 0/00 lower prior to the Last Glacial Maximum than at present, a response
      almost identical to that of nonherbaceous taxa from lower elevations. However,
      initial shifts in Delta aligned most closely with the onset of the late
      Pleistocene bipolar temperature "seesaw" rather than CO2 increase, indicating
      unique limitations on glacial-age high-elevation plants may have existed due to
      both low temperatures and low CO2. Further development of system-specific faunal
      proxies can help to clarify this and other plant- and ecosystem-level responses
      to past environmental change.

PMID- 24916835
TI  - Zonisamide attenuates hyperoxia-induced apoptosis in the developing rat brain.
AB  - Oxygen therapy used in the treatment of perinatal hypoxia induces
      neurodegeneration in babies with immature antioxidant mechanisms. Zonisamide is a
      new antiepileptic drug used in childhood intractable seizures. Many studies
      demonstrated its neuroprotective effects. There is no study evaluating its effect
      on hyperoxic brain injury. The aim of this study was to investigate the
      neuroprotective effect of zonisamide on hyperoxia-induced neonatal brain injury.
      A total of 21 Wistar rat pups were used. The animals were divided into three
      groups: control group, hyperoxia group, and zonisamide-treated group. The
      zonisamide-treated group received an intraperitoneal injection of zonisamide.
      Zonisamide significantly preserved the number of neurons in CA1 and dentate gyrus
      parts of hippocampus, prefrontal, and parietal cortex. Zonisamide treatment also
      decreased the number of apoptotic neurons in all examined parts of hippocampus,
      prefrontal, and parietal cortex. We suggest that zonisamide treatment may be used
      as a neuroprotective agent in hyperoxic brain injury. 

PMID- 24916836
TI  - Vestibular evoked myogenic potentials in Bell's palsy.
AB  - The aim of the present study was to evaluate vestibular nerve involvement in
      patients with Bell's palsy with ocular and cervical vestibular evoked myogenic
      potentials (oVEMP and cVEMP). Ten patients who were diagnosed with Bell's palsy
      and ten healthy controls were included. All patients underwent VEMP recordings
      within 6 days after their initial presentation. Patients with Bell's palsy had
      greater oVEMP asymmetry ratio comparing to healthy controls (-38.4 +/- 28.7 % vs 
      1.3 +/- 19.3 %, p = 0.005). As well N10 latencies of the oVEMP response were
      prolonged comparing to healthy controls (11.575 vs 9.72 ms). There was no
      difference in cVEMP asymmetry ratio or latencies between groups. We found no
      correlation between House-Brackmann grading scale and oVEMP asymmetry ratio (r =
      0.003, p = 0.994). There are three possible explanations for increased oVEMP
      amplitudes on the affected side: (1) oVEMP response on the ipsilateral eye could
      be contaminated by facial nerve activity (blink reflex); (2) the amplitude of N10
      P33 could be affected through the stapedial reflex; and (3) increased oVEMP
      amplitude could be the consequence of the vestibular nerve dysfunction itself,
      with prolonged latencies of the N10 oVEMP further supporting this explanation.
      The results of this study indicate possible involvement of the superior branch of
      the vestibular nerve in patients with Bell's palsy.

PMID- 24916837
TI  - Cognitive and affective influences on perceived risk of ovarian cancer.
AB  - INTRODUCTION: Studies suggest that both affective and cognitive processes are
      involved in the perception of vulnerability to cancer and that affect has an
      early influence in this assessment of risk. We constructed a path model based on
      a conceptual framework of heuristic reasoning (affect, resemblance, and
      availability) coupled with cognitive processes involved in developing personal
      models of cancer causation. METHODS: From an eligible cohort of 16 700 women in a
      managed care organization, we randomly selected 2524 women at high, elevated, and
      average risk of ovarian cancer and administered a questionnaire to test our model
      (response rate 76.3%). Path analysis delineated the relationships between
      personal and cognitive characteristics (number of relatives with cancer, age,
      ideas about cancer causation, perceived resemblance to an affected friend or
      relative, and ovarian cancer knowledge) and emotional constructs (closeness to an
      affected relative or friend, time spent processing the cancer experience, and
      cancer worry) on perceived risk of ovarian cancer. RESULTS: Our final model fit
      the data well (root mean square error of approximation (RMSEA) = 0.028,
      comparative fit index (CFI) = 0.99, normed fit index (NFI) = 0.98). This final
      model (1) demonstrated the nature and direction of relationships between
      cognitive characteristics and perceived risk; (2) showed that time spent
      processing the cancer experience was associated with cancer worry; and (3) showed
      that cancer worry moderately influenced perceived risk. DISCUSSION: Our results
      highlight the important role that family cancer experience has on cancer worry
      and shows how cancer experience translates into personal risk perceptions. This
      understanding informs the discordance between medical or objective risk
      assessment and personal risk assessment. Published in 2014. This article is a
      U.S. Government work and is in the public domain in the USA.

PMID- 24916838
TI  - A comparison of continuous intravenous insulin and subcutaneous insulin among
      patients with type 2 diabetes and congestive heart failure exacerbation.
AB  - BACKGROUND: The study aims to determine whether the route of insulin
      administration influences glycaemic variability and inflammatory or neurohormonal
      markers in patients with type 2 diabetes and congestive heart failure (CHF)
      exacerbation. METHODS: Patients (n = 65) were randomized to intravenous (IV)
      insulin (duration 48 h) or subcutaneous (SQ) insulin. Inflammatory cytokines and
      markers of lipid oxidation, high-frequency heart rate variability (n = 27) and
      cardiac impedance (pre-ejection period, n = 28) were used to estimate
      parasympathetic and sympathetic tone in patients with valid cardiac data.
      Glycaemic variability was measured using a continuous glucose monitor. RESULTS:
      Mean glucose was lower (7.7 +/- 1.2 vs 9.4 +/- 2.7 mmol/L, p = 0.004),
      coefficient of variation was higher (p = 0.03) and glycaemic lability index was
      similar on day 1 in the IV group compared with the SQ group, but groups were
      similar by day 2. The IV group had more confirmed hypoglycaemia (p = 0.005).
      There were no differences in hospital readmission or hospital length of stay
      between groups. There were no differences in CHF biomarkers, heart rate
      variability or pre-ejection period between groups. Increasing log glycaemic
      lability index was associated with lower on-treatment pre-ejection period (p =
      0.03) while increasing coefficient of variation was associated with increasing
      brain natriuretic peptide (p = 0.004) and paroxonase-1 (p = 0.02). Other
      univariable analyses were not significant. CONCLUSIONS: There were modest,
      transient differences in glucose control between IV and SQ insulin in
      hospitalized CHF patients. However, the analyses do not support a link between
      insulin route and inflammatory markers or autonomic tone. Further study is needed
      to assess outcomes in hospitalized CHF patients.

PMID- 24916839
TI  - Maximum linkage space-time permutation scan statistics for disease outbreak
      detection.
AB  - BACKGROUND: In disease surveillance, the prospective space-time permutation scan
      statistic is commonly used for the early detection of disease outbreaks. The
      scanning window that defines potential clusters of diseases is cylindrical in
      shape, which does not allow incorporating into the cluster shape potential
      factors that can contribute to the spread of the disease, such as information
      about roads, landscape, among others. Furthermore, the cylinder scanning window
      assumes that the spatial extent of the cluster does not change in time.
      Alternatively, a dynamic space-time cluster may indicate the potential spread of
      the disease through time. For instance, the cluster may decrease over time
      indicating that the spread of the disease is vanishing. METHODS: This paper
      proposes two irregularly shaped space-time permutation scan statistics. The
      cluster geometry is dynamically created using a graph structure. The graph can be
      created to include nearest-neighbor structures, geographical adjacency
      information or any relevant prior information regarding the contagious behavior
      of the event under surveillance. RESULTS: The new methods are illustrated using
      influenza cases in three New England states, and compared with the cylindrical
      version. A simulation study is provided to investigate some properties of the
      proposed arbitrary cluster detection techniques. CONCLUSION: We have successfully
      developed two new space-time permutation scan statistics methods with irregular
      shapes and improved computational performance. The results demonstrate the
      potential of these methods to quickly detect disease outbreaks with irregular
      geometries. Future work aims at performing intensive simulation studies to
      evaluate the proposed methods using different scenarios, number of cases, and
      graph structures.

PMID- 24916840
TI  - Milk and dairy consumption and risk of dementia in an elderly Japanese
      population: the Hisayama Study.
AB  - OBJECTIVES: To determine the effect of milk and dairy intake on the development
      of all-cause dementia and its subtypes in an elderly Japanese population. DESIGN:
      Prospective cohort study. SETTING: The Hisayama Study, Japan. PARTICIPANTS:
      Individuals aged 60 and older without dementia (N = 1,081). MEASUREMENTS: Milk
      and dairy intake was estimated using a 70-item semiquantitative food frequency
      questionnaire grouped into quartiles. The risk estimates of milk and dairy intake
      on the development of all-cause dementia, Alzheimer's disease (AD), and vascular
      dementia (VaD) were computed using a Cox proportional hazards model. RESULTS:
      Over 17 years of follow-up, 303 subjects developed all-cause dementia; 166 had
      AD, and 98 had VaD. The age- and sex-adjusted incidence of all-cause dementia,
      AD, and VaD significantly decreased as milk and dairy intake level increased (P
      for trend = .03 for all-cause dementia, .04 for AD, .01 for VaD). After adjusting
      for potential confounders, the linear relationship between milk and dairy intake
      and development of AD remained significant (P for trend = .03), whereas the
      relationships with all-cause dementia and VaD were not significant. The risk of
      AD was significantly lower in the second, third, and fourth quartiles of milk and
      dairy intake than in the first quartile. CONCLUSION: Greater milk and dairy
      intake reduced the risk of dementia, especially AD, in the general Japanese
      population.

PMID- 24916841
TI  - Smartphones for cell and biomolecular detection.
AB  - Recent advances in biomedical science and technology have played a significant
      role in the development of new sensors and assays for cell and biomolecular
      detection. Generally, these efforts are aimed at reducing the complexity and
      costs associated with diagnostic testing so that it can be performed outside of a
      laboratory or hospital setting, requiring minimal equipment and user involvement.
      In particular, point-of-care (POC) testing offers immense potential for many
      important applications including medical diagnosis, environmental monitoring,
      food safety, and biosecurity. When coupled with smartphones, POC systems can
      offer portability, ease of use and enhanced functionality while maintaining
      performance. This review article focuses on recent advancements and developments
      in smartphone-based POC systems within the last 6 years with an emphasis on cell
      and biomolecular detection. These devices typically comprise multiple components,
      such as detectors, sample processors, disposable chips, batteries, and software,
      which are integrated with a commercial smartphone. One of the most important
      aspects of developing these systems is the integration of these components onto a
      compact and lightweight platform that requires minimal power. Researchers have
      demonstrated several promising approaches employing various detection schemes and
      device configurations, and it is expected that further developments in
      biosensors, battery technology and miniaturized electronics will enable
      smartphone-based POC technologies to become more mainstream tools in the
      scientific and biomedical communities. 

PMID- 24916842
TI  - Identification of a novel overlapping sequential E epitope (E') on the bovine
      leukaemia virus SU glycoprotein and analysis of immunological data.
AB  - Bovine leukaemia virus (BLV), an oncogenic C-type retrovirus, is the causative
      agent of enzootic bovine leucosis. Binding of BLV to its cellular receptor is
      mediated by the surface envelope glycoprotein subunit (SU). Previous studies have
      identified eight different epitopes (A through H) on the BLV SU. In this study, a
      new sequential epitope was identified using the monoclonal antibody 2G7 (MAb 2G7)
      on the C-terminal region of the BLV SU. To localise and refine the map of this
      epitope, a series of deleted forms in the C and N-terminal ends of the
      glycoprotein were made and synthesised in baculovirus and Escherichia coli
      expression systems. The synthetic proteins were analysed both in Western blot and
      MAb-capture ELISA assays. MAb 2G7 recognised a stretch of 11 amino acids, named
      epitope E', corresponding to residues 189-SDWVPSVRSWA-199 (comprising the 33
      amino acids signal peptide) overlapping with the E epitope of the SU. The data
      obtained by Enzyme-Linked Immunosorbent Assay (ELISA) revealed that the E'
      epitope was hidden on whole BLV particles and that the variation in reactivity
      between epitope E' and MAb 2G7 depends on the glycosylation state of SU.
      Similarly, the analysis of immunological data evidenced that the failure of
      interaction between the MAb anti-DD' and its epitope was also due to a steric
      hindrance of the glycosylation. Finally, the ELISA assay analysis performed with
      the deleted and mutated forms of rSU evidenced that the conformational epitopes
      F, G and H lied into in the 34-173 amino-acids residues of N-terminal region of
      SU. 

PMID- 24916843
TI  - The complex role of DNA, histones and HMGB1 in the pathogenesis of SLE.
AB  - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease
      characterized by the production of antinuclear antibodies (ANA) in association
      with protean clinic manifestations. ANA can bind to nuclear molecules, most
      prominently DNA and histones in nucleosomes, to form complexes to promote
      pathogenesis. Because of the intrinsic immunological activity of the nuclear
      components, these complexes can amplify responses by interacting with diverse
      pattern recognition receptors and internal sensing systems. Among molecules
      associated with nucleosomal components, HMGB1, a non-histone protein, can emanate
      from activated and dying cells; HMGB1's immune activity is determined by post
      translational modifications, redox state, and binding to other immune mediators.
      Although ANAs form complexes that deposit in the kidney or induce type 1
      interferon, ANAs may also block immune activity. Together, these studies
      highlight the importance of complexes in the pathogenesis of lupus and their role
      as antigens, immunogens, and adjuvants.

PMID- 24916844
TI  - Excited state potential energy surfaces and their interactions in Fe(IV)=O active
      sites.
AB  - The non-heme ferryl active sites are of significant interest for their
      application in biomedical and green catalysis. These sites have been shown to
      have an S = 1 or S = 2 ground spin state; the latter is functional in biology.
      Low-temperature magnetic circular dichroism (LT MCD) spectroscopy probes the
      nature of the excited states in these species including ligand-field (LF) states
      that are otherwise difficult to study by other spectroscopies. In particular, the
      temperature dependences of MCD features enable their unambiguous assignment and
      thus determination of the low-lying excited states in two prototypical S = 1 and
      S = 2 NHFe(IV)[double bond, length as m-dash]O complexes. Furthermore, some MCD
      bands exhibit vibronic structures that allow mapping of excited-state
      interactions and their effects on the potential energy surfaces (PESs). For the S
      = 2 species, there is also an unusual spectral feature in both near-infrared
      absorption and MCD spectra - Fano antiresonance (dip in Abs) and Fano resonance
      (sharp peak in MCD) that indicates the weak spin-orbit coupling of an S = 1 state
      with the S = 2 LF state. These experimental data are correlated with quantum
      chemical calculations that are further extended to analyze the low-lying
      electronic states and the evolution of their multiconfigurational characters
      along the Fe-O PESs. These investigations show that the lowest-energy states
      develop oxyl Fe(III) character at distances that are relevant to the transition
      state (TS) for H-atom abstraction and define the frontier molecular orbitals that
      participate in the reactivity of S = 1 vs. S = 2 non-heme Fe(IV)[double bond,
      length as m-dash]O active sites. The S = 1 species has only one available channel
      that requires the C-H bond of a substrate to approach perpendicular to the Fe-oxo
      bond (the pi channel). In contrast, there are three channels (one sigma and two
      pi) available for the S = 2 non-heme Fe(IV)[double bond, length as m-dash]O
      system allowing C-H substrate approach both along and perpendicular to the Fe-oxo
      bond that have important implications for enzymatic selectivity. 

PMID- 24916846
TI  - Prostate cancer survivorship guidelines.

PMID- 24916845
TI  - Identification of a subtype-specific ENC1 gene related to invasiveness in human
      pituitary null cell adenoma and oncocytomas.
AB  - Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Surgery is a
      treatment option, but unlike the case for functional pituitary adenomas, there
      are almost no drug treatments available for NFPAs. Markers of invasiveness are
      needed to guide therapeutic decision-making and identify potential adjuvant
      drugs. Owing to the highly heterogeneous nature of NFPAs, little is known
      regarding the subtype-specific gene expression profiles associated with
      invasiveness. To identify important biomarkers of invasiveness, we selected 23
      null cell adenomas and 20 oncocytomas. These tumors were classified as invasive
      or non-invasive adenomas based on magnetic resonance imaging, pathology slides
      and surgical findings. Firstly, we observed that there were significant
      differences in expression between invasive (n = 3) and non-invasive (n = 4)
      adenomas by gene expression microarray. A total of 1,188 genes were
      differentially expressed in the invasive and non-invasive adenomas. Among these
      1,188 genes, 578 were upregulated and 610 were downregulated in invasive
      adenomas. Secondly, the expression of ENC1, which displayed the significant
      alterations, was further confirmed by qRT-PCR and Western blot analysis in all 43
      tumor samples and three normal pituitary glands. Low levels of ENC1 were found in
      tumor samples, while high levels were detected in normal pituitary glands.
      Interestingly, the ENC1 expression level was low in invasive null cell adenomas
      compared with non-invasive adenomas, but this relationship was not observed in
      invasive oncocytomas. Immunohistochemistry also demonstrated that the staining of
      ENC1 was different between invasive and non-invasive null cell adenomas. In
      addition, bioinformatics studies, including gene ontology and protein interaction
      analyses, were also performed to better understand the critical role of ENC1 in
      the development and progression of null cell adenomas and oncocytomas.
      Consequently, ENC1 may be an important biomarker for null cell adenomas and
      oncocytomas, and it is specific to invasive null cell adenomas.

PMID- 24916847
TI  - Implantable rhythm devices in the management of vasovagal syncope.
AB  - The ECG registration during syncope allows physicians either to confirm or
      exclude an arrhythmia as the mechanism of syncope. Implantable loop recorders
      have an over-writeable memory buffer that continuously records and deletes the
      patient's ECG for up to three years. Many studies have analyzed the utility of
      implantable loop recorders in recurrent unexplained or high risk syncope. These
      studies suggest that early use of the ILR provides more and earlier diagnoses and
      could help in selecting patients with vasovagal syncope and prolonged asystolic
      pauses who might benefit from pacemaker therapy. However many questions remain,
      including its performance in the community by physicians with a range of
      experience in diagnosing syncope. Furthermore there is no evidence that the use
      of the ILR changes outcome. Numerous attempts have been made to determine whether
      patients with predominantly cardioinhibitory syncope benefit from permanent
      pacemakers, especially if symptoms are frequent and debilitating. While the first
      open label trials of pacemakers in the treatment of vasovagal syncope showed
      promising results, this effect has not been confirmed by blinded randomized
      clinical trials. More recent data seem to suggest that patients over 40years with
      severe asystolic vasovagal syncope might benefit from permanent pacemakers. 

PMID- 24916848
TI  - Hypomyelinating leukodystrophies: translational research progress and prospects.
AB  - Hypomyelinating leukodystrophies represent a genetically heterogeneous but
      clinically overlapping group of heritable disorders. Current management
      approaches in the care of the patient with a hypomyelinating leukodystrophy
      include use of serial magnetic resonance imaging (MRI) to establish and monitor
      hypomyelination, molecular diagnostics to determine a specific etiology, and
      equally importantly, careful attention to neurologic complications over time.
      Emerging research in oligodendrocyte biology and neuroradiology with bedside
      applications may result in the possibility of clinical trials in the near term,
      yet there are significant gaps in knowledge in disease classification,
      characterization, and outcome measures in this group of disorders. Here we review
      the biological background of myelination, the clinical and genetic variability in
      hypomyelinating leukodystrophies, and the insights that can be obtained from
      current MRI techniques. In addition, we discuss ongoing research approaches to
      define potential outcome markers for future clinical trials.

PMID- 24916849
TI  - Deep sequencing reveals a novel class of bidirectional promoters associated with
      neuronal genes.
AB  - BACKGROUND: Comprehensive annotation of transcripts expressed in a given tissue
      is a critical step towards the understanding of regulatory and functional
      pathways that shape the transcriptome. RESULTS: Here, we reconstructed a
      cumulative transcriptome of the human prefrontal cortex (PFC) based on
      approximately 300 million strand-specific RNA sequence (RNA-seq) reads collected
      at different stages of postnatal development. We find that more than 50% of
      reconstructed transcripts represent novel transcriptome elements, including 8,343
      novel exons and exon extensions of annotated coding genes, 11,217 novel antisense
      transcripts and 29,541 novel intergenic transcripts or their fragments showing
      canonical features of long non-coding RNAs (lncRNAs). Our analysis further led to
      a surprising discovery of a novel class of bidirectional promoters (NBiPs)
      driving divergent transcription of mRNA and novel lncRNA pairs and displaying a
      distinct set of sequence and epigenetic features. In contrast to known
      bidirectional and unidirectional promoters, NBiPs are strongly associated with
      genes involved in neuronal functions and regulated by neuron-associated
      transcription factors. CONCLUSIONS: Taken together, our results demonstrate that
      large portions of the human transcriptome remain uncharacterized. The distinct
      sequence and epigenetic features of NBiPs, as well as their specific association
      with neuronal genes, further suggest existence of regulatory pathways specific to
      the human brain.

PMID- 24916850
TI  - An internal performance assessment of CancerGene Connect: an electronic tool to
      streamline, measure and improve the genetic counseling process.
AB  - CancerGene Connect (CGC) is a web-based program that combines the collection of
      family and medical history, cancer risk assessment, psychosocial assessment,
      report templates, a result tracking system, and a patient follow up system. The
      performance of CGC was assessed in several ways: pre-appointment completion data
      analyzed for demographic and health variables; a time study to assess overall
      time per case and to compare the data entry by the genetic counselor compared to
      the patient, and a measured quality assessment of the program via observation and
      interview of patients. Prior to their appointment, 52.3% of 2,414 patients
      completed the online patient questionnaire section of CGC. There were significant
      differences in completion rates among racial and ethnic groups. County hospital
      patients were less likely to complete the questionnaire than insured patients (p
      < 0.0001); and likewise uninsured patients and patients with Medicare/Medicaid
      were less likely to complete the questionnaire than private patients (p <
      0.0001). The average genetic counseling time per case was 82 min, with no
      significant differences whether the counselor or the patient completed CGC. CGC
      reduces genetic counselor time by approximately 14-46% compared to average time
      per case using traditional risk assessment and documentation methods previously
      reported. All surveyed users felt the questionnaire was easy to understand. CGC
      is an effective tool that streamlines workflow, and provides a standardized data
      collection tool that can be used to evaluate and improve the genetic counseling
      process.

PMID- 24916851
TI  - Metals and nonsteroidal anti-inflammatory pharmaceuticals drugs present in water
      from Madin Reservoir (Mexico) induce oxidative stress in gill, blood, and muscle
      of common carp (Cyprinus carpio).
AB  - Many toxic xenobiotics that enter the aquatic environment exert their effects
      through redox cycling. Oxidative stress, which incorporates both oxidative damage
      and antioxidant defenses, is a common effect induced in organisms exposed to
      xenobiotics in their environment. The results of the present study aimed to
      determine the oxidative stress induced in the common carp Cyprinus carpio by
      contaminants [metals and nonsteroidal anti-inflammatory drugs (NSAIDs)] present
      in Madin Reservoir. Five sampling stations (SSs), considered to have the most
      problems due to discharges, were selected. Carp were exposed to water from each
      SS for 96 h, and the following biomarkers were evaluated in gill, blood, and
      muscle: hydroperoxide content, lipid peroxidation, protein carbonyl content, and
      the activity of antioxidant enzymes superoxide dismutase and catalase. Results
      show that contaminants (metals and NSAIDs) present in water from the different
      SSs induce oxidative stress. Thus, water in this reservoir is contaminated with
      xenobiotics that are hazardous to C. carpio, a species consumed by the local
      human population.

PMID- 24916852
TI  - A high birth weight is associated with increased risk of type 2 diabetes and
      obesity.
AB  - BACKGROUND: The association between low birth weight and adult disease is well
      known. Less is known on long-term effects of high birth weight. OBJECTIVE: This
      study aims to investigate whether a high birth weight increases risk for adult
      metabolic disease. METHODS: Swedish term single births, 1973-1982 (n = 759,999),
      were studied to age 27.5-37.5 years using Swedish national registers. Hazard
      ratios (HRs) were calculated in relation to birth weight for type 2 diabetes,
      obesity, hypertension and dyslipidaemia. RESULTS: Men with birth weights between
      2 and 3 standard deviation score (SDS) had a 1.9-fold increased risk (HR 1.91,
      95% confidence interval [CI] 1.25-2.90) of type 2 diabetes, whereas those with
      birth weights above 3 SDS had a 5.4-fold increased risk (HR 5.44, 95% CI 2.70
      10.96) compared to men with birth weights between -2 and 2 SDS. The corresponding
      HRs for women were 0.60 (95% CI 0.40-0.91) and 1.71 (95% CI 0.85-3.43) for birth
      weights 2-3 SDS and >3 SDS, respectively. Men with birth weights between 2 and 3
      SDS had a 1.5-fold increased risk (HR 1.47, 95% CI 1.22-1.77) of obesity. The
      corresponding risk for women was 1.3-fold increased (HR 1.32, 95% CI 1.19-1.46).
      For men and women with birth weights above 3 SDS, the risks of adult obesity were
      higher, HR 2.46 (95% CI 1.63-3.71) and HR 1.85 (95% CI 1.44-2.37), respectively.
      CONCLUSIONS: A high birth weight, particularly very high, increases the risk of
      type 2 diabetes in male young adults. The risk of obesity increases with
      increasing birth weight in both genders.

PMID- 24916854
TI  - Applied computational chemistry.

PMID- 24916853
TI  - Higher clinical success in patients with ventilator-associated pneumonia due to
      methicillin-resistant Staphylococcus aureus treated with linezolid compared with
      vancomycin: results from the IMPACT-HAP study.
AB  - INTRODUCTION: Controversy exists regarding optimal treatment for ventilator
      associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus
      (MRSA). The primary objective of this study was to compare clinical success of
      linezolid versus vancomycin for the treatment of patients with MRSA VAP. METHODS:
      This was a multicenter, retrospective, observational study of patients with VAP
      (defined according to Centers for Disease Control and Prevention criteria) due to
      MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when
      MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical
      success was evaluated by assessing improvement or resolution of signs and
      symptoms of VAP by day 14. After matching on confounding factors, logistic
      regression models were used to determine if an association existed between
      treatment arm and clinical success. RESULTS: A total of 188 patients were
      evaluated (101 treated with linezolid and 87 with vancomycin). The mean +/-
      standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II
      score was 21 +/- 11 for linezolid- and 19 +/- 9 for vancomycin-treated patients
      (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients
      compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for
      confounding factors, linezolid-treated patients were 24% more likely to
      experience clinical success than vancomycin-treated patients (P = 0.018).
      CONCLUSIONS: This study adds to the evidence indicating that patients with MRSA
      VAP who are treated with linezolid are more likely to respond favorably compared
      with patients treated with vancomycin.

PMID- 24916855
TI  - A systematic approach to definitive planning and designing single and multiple
      unit implant abutments.
AB  - With an increase in the availability of implant restorative components, the
      selection of an appropriate implant abutment for a given clinical situation has
      become more challenging. This article describes a systematic protocol to help the
      practitioner more thoughtfully select abutments for single and multiple unit
      fixed implant prostheses. The article examines the evaluation, planning, design,
      and fabrication processes for the definitive restoration. It includes an
      assessment of a variety of factors, namely restorative space, soft and hard
      tissues, the location of the implant platform, the type of platform connection,
      platform switching indications, tissue collar heights, emergence profile, implant
      angulation, and finally the design and esthetic options for the final implant
      abutment. 

PMID- 24916857
TI  - Adjustment of web-building initiation to high humidity: a constraint by humidity
      dependent thread stickiness in the spider Cyrtarachne.
AB  - Cyrtarachne is an orb-weaving spider belonging to the subfamily Cyrtarachninae
      (Araneidae) which includes triangular-web-building Pasilobus and bolas spiders.
      The Cyrtarachninae is a group of spiders specialized in catching moths, which is
      thought to have evolved from ordinary orb-weaving araneids. Although the web
      building time of nocturnal spiders is in general related to the time of sunset,
      anecdotal evidence has suggested variability of web-building time in Cyrtarachne
      and its closely related genera. This study has examined the effects of
      temperature, humidity, moonlight intensity, and prey (moths) availability on web
      building time of Cyrtarachne bufo, Cyrtarachne akirai, and Cyrtarachne
      nagasakiensis. Generalized linear mixed model (GLMM) have revealed that humidity,
      and not prey availability, was the essential variable that explained the daily
      variability of web-building time. Experiments measuring thread stickiness under
      different humidities showed that, although the thread of Cyrtarachne was found to
      have strong stickiness under high humidity, low humidity caused a marked decrease
      of thread stickiness. By contrast, no obvious change in stickiness was seen in an
      ordinary orb-weaving spider, Larinia argiopiformis. These findings suggest that
      Cyrtarachne adjusts its web-building time to favorable conditions of high
      humidity maintaining strong stickiness, which enables the threads to work
      efficiently for capturing prey. 

PMID- 24916856
TI  - Reactive microglia and macrophage facilitate the formation of Muller glia-derived
      retinal progenitors.
AB  - In retinas where Muller glia have been stimulated to become progenitor cells,
      reactive microglia are always present. Thus, we investigated how the activation
      or ablation of microglia/macrophage influences the formation of Muller glia
      derived progenitor cells (MGPCs) in the retina in vivo. Intraocular injections of
      the Interleukin-6 (IL6) stimulated the reactivity of microglia/macrophage,
      whereas other types of retinal glia appear largely unaffected. In acutely damaged
      retinas where all of the retinal microglia/macrophage were ablated, the formation
      of proliferating MGPCs was greatly diminished. With the microglia ablated in
      damaged retinas, levels of Notch and related genes were unchanged or increased,
      whereas levels of ascl1a, TNFalpha, IL1beta, complement component 3 (C3) and C3a
      receptor were significantly reduced. In the absence of retinal damage, the
      combination of insulin and Fibroblast growth factor 2 (FGF2) failed to stimulate
      the formation of MGPCs when the microglia/macrophage were ablated. In addition,
      intraocular injections of IL6 and FGF2 stimulated the formation of MGPCs in the
      absence of retinal damage, and this generation of MGPCs was blocked when the
      microglia/macrophage were absent. We conclude that the activation of microglia
      and/or infiltrating macrophage contributes to the formation of proliferating
      MGPCs, and these effects may be mediated by components of the complement system
      and inflammatory cytokines.

PMID- 24916858
TI  - High diagnostic stability of confirmed migraine and confirmed tension-type
      headache according to the ICHD-3 beta in adolescents.
AB  - BACKGROUND: Stable headache diagnosis classification is a prerequisite for
      identification of headache type specific risk factors. Does the stability of a
      headache diagnosis over time vary between migraine and tension-type headache
      (TTH)? Are there differences in diagnosis stability between a probable and a
      definite headache diagnosis? FINDINGS: In a sample of 783 students (ages 12 to 18
      years) participating in a headache intervention study in greater Munich, the
      stability of headache classification according to the International
      Classification of Headache Disorder - third edition (beta version) (ICHD-3 beta)
      after a follow-up of 7 months was examined. Differences in stability of probable
      or definite migraine and probable or definite TTH were assessed. The stability of
      the headache diagnosis was assessed as predictive value of headache diagnosis
      with regard to confirmation of the headache type using the same diagnostic
      instrument 7 months later. Predictive values with 95% confidence intervals (CI)
      are reported.Of students with initial migraine, a diagnosis of migraine was
      confirmed in 65.71% of students after 7 months (95%-CI [59.40-71.64]). A clear
      distinction between probable (44.71%, 95%-CI [33.91-53.89]) and confirmed
      diagnosis (76.88% 95%-CI [69.56-83.17]) of migraine was observed. For TTH the
      predictive value was 62.66% (95%-CI [57.07-68.01]) overall with a lower stability
      for probable (46.10%, 95%-CI [37.68-54.69]) compared to the confirmed diagnosis
      (69.71%, 95%-CI [23.58-37.67]). CONCLUSION: While confirmed migraine and
      confirmed TTH diagnoses seem stable over time, stability of a probable diagnosis
      for either headache type was lower. TRIAL REGISTRATION: The trial was registered
      at the German Clinical Trial Register with the ID DRKS00003308.

PMID- 24916859
TI  - The complete mitochondrial genome sequence of Brassica oleracea and analysis of
      coexisting mitotypes.
AB  - The complete mitochondrial genome sequences of Brassica species have provided
      insight into inter- and intraspecific variation of plant mitochondrial genomes.
      However, the size of mitochondrial genome sequenced for Brassica oleracea
      hitherto does not match to its physical mapping data. This fact led us to
      investigate B. oleracea mitochondrial genome in detail. Here we report novel B.
      oleracea mitochondrial genome, derived from var. capitata, a cabbage cultivar
      ''Fujiwase''. The genome was assembled into a 219,952-bp circular sequence that
      is comparable to the mitochondrial genomes of other Brassica species (ca. 220-232
      kb). This genome contained 34 protein-coding genes, 3 rRNA genes and 17 tRNA
      genes. Due to absence of a large repeat (140 kb), the mitochondrial genome of
      ''Fujiwase'' is clearly smaller than the previously reported mitochondrial genome
      of B. oleracea accession ''08C717'' (360 kb). In both mitotypes, all genes were
      identical, except cox2-2, which was present only in the Fujiwase type. At least
      two rearrangement events via large and small repeat sequences have contributed to
      the structural differences between the two mitotypes. PCR-based marker analysis
      revealed that the Fujiwase type is predominant, whereas the 08C717 type coexists
      at low frequency in all B. oleracea cultivars examined. Intraspecific variations
      in the mitochondrial genome in B. oleracea may occur because of heteroplasmy,
      coexistence of different mitotypes within an individual, and substoichiometric
      shifting. Our data indicate that the Fujiwase-type genome should be used as the
      representative genome of B. oleracea.

PMID- 24916860
TI  - Effects of particle size and moisture levels in mixed rations on the feeding
      behavior of dairy heifers.
AB  - Two experiments on replacement heifers (175+/-12 days of age) assessed the
      effects of forage particle length and moisture on feeding behavior. Both
      experiments used a replicated 3*3 Latin square design, with nine heifers per
      replication and three periods of 9 days each. Each group of nine heifers was
      housed in one pen with access to three electronic feed bins. In Experiment 1, hay
      chopped at different lengths was incorporated into three total mixed rations
      (TMR) all having the same ingredient and nutrient composition but differing in
      the percentage of long particles (>19 mm): 60% (Short), 64% (Medium) and 72%
      (Long). In Experiment 2, heifers were fed a TMR with the same ingredient and
      nutrient composition but differing in moisture content: 65% DM (Dry), 50% DM
      (Moderate), and 35% DM (Wet). In both experiments, feeding behavior during the
      last 5 days of each period was analyzed using a mixed model accounting for the
      fixed effects of treatment and period, and the random effects of replication and
      animal. In Experiment 1, dry matter intake (DMI) and eating rate (DMI/min) tended
      to increase, whereas daily eating time decreased as the feed particle size
      decreased. Heifers fed the Long diet selected in favor of long particles (>19 mm)
      and against Short (1.18 to 8 mm) and fine (<1.18 mm) particles; heifers fed the
      Short diet selected against long particles and in favor of short and fine
      particles. Heifers fed the Medium diet showed a preference for medium particles
      with no preference for the other particle sizes. In Experiment 2, heifers fed the
      Dry diet tended to consume more feed than those fed the Moderate and Wet diets,
      with no differences in feeding behavior or sorting activity. In conclusion the
      Medium diet minimized sorting without reducing eating rates and intake, and
      adding water to TMR to achieve a dry matter less than 65% tended to decrease DMI
      without reducing sorting.

PMID- 24916861
TI  - The use of computerized tomography in determining stature and sex from metatarsal
      bones.
AB  - This study evaluates the efficacy of a radiological method to estimate stature
      from measurements of the first and second metatarsal taken from a collection of
      metatarsals of a Portuguese Caucasian population in which the measurements were
      made directly on the bone. The highest coefficient of determination and the
      lowest standard error were obtained with the physiological length of the second
      metatarsal (F2), using the equation S=895.4803+10.7848F2. The linear regressions
      obtained show significant differences between the estimated heights from M1. In
      addition, we offer a simple method for sex determination based on the maximum
      length (M1) and width (W1) of the first metatarsal, where W1=x1; (M1/W1)=x2;
      beta0=55.4767; beta1=-2.5796 and beta2=-4.6898. Here we present a method of
      measurement using computerized tomography that enables population studies using
      live volunteers without incurring the difficulties of on the bone measurement.

PMID- 24916862
TI  - New pitfalls of high-density postmortem computed tomography.
AB  - An 80-year-old female was transferred to the hospital due to a traffic accident.
      Multiple cranial bone fractures with intracranial hemorrhage and intracranial air
      were detected. Despite treatment, the patient died after 6h. Twenty-one hours
      after the patient died, her whole body was scanned by postmortem CT, and a region
      of high density was detected within the left putamen. The autopsy revealed a
      cerebral contusion and multiple skull base fractures. Moreover, superabsorbent
      polymers (SAPs) were found within the left lateral ventricle and adjacent to the
      putamen, which appeared as a high-density lesion on postmortem CT at the left
      putamen, where the SAPs were compacted. Both ante- and postmortem conditions
      should be considered to prevent misdiagnoses based only on postmortem CT. 

PMID- 24916863
TI  - A fatal case of adult small bowel volvulus.
AB  - A 56-year-old man was hit by a car while riding a bicycle, immediately brought to
      the hospital, and treated. Four days after the accident, he reported abdominal
      pain and vomiting in the night, and he died the next day. A forensic autopsy was
      performed, and almost of the entire small bowel had gangrenous swelling. The
      mesentery was twisted 180 degrees  with clockwise rotation along the vascular
      axis, and pre-autopsy computed tomography scan showed a whirl sign. 

PMID- 24916864
TI  - Typhoid fever: misuse of Widal test in Libya.
AB  - The worldwide gold standard of diagnosing of enteric fever depends on the
      isolation of Salmonella enterica serovar Typhi from a patient's bone marrow
      and/or blood culture. In Libya clinicians are heavily dependent on the Widal test
      for diagnosis of enteric fever which has been used without determining the
      locally appropriate threshold titer, because the laboratories lack the skilled,
      experienced personnel and appropriate facilities to detect and serotype
      Salmonella isolates. To improve the diagnosis process, clinical management and
      reliability of public health measures, there is an urgent need for the effective
      training of laboratory technicians and to provide resources to culture Salmonella
      species according to published guidelines. Clinicians should understand the
      limitations of Widal test and recognize that it cannot be expected to give a
      reliable diagnosis. 

PMID- 24916865
TI  - Molecular identification of the ompL1 gene within Leptospira interrogans standard
      serovars.
AB  - INTRODUCTION: Leptospirosis, caused by infection with pathogenic Leptospira
      species, is one of the most prevalent zoonotic diseases in the world. Current
      leptospiral vaccines are mainly multivalent dead whole-cell mixtures made of
      several local dominant serovars. Therefore, design and construction of an
      efficient recombinant vaccine for leptospirosis control is very important. OmpL1
      is an immunogenic porin protein that could be of special significance in
      vaccination and serodiagnosis for leptospirosis. METHODOLOGY: Three strains
      belonging to pathogenic L. interrogans were analyzed. The specific primers for
      proliferation of the ompL1 gene were designed. The amplified gene was cloned. In
      order to investigate the ompL1 nucleotide sequence and homological analysis of
      this gene, ompL1 genes cloned from standard vaccinal Leptospira serovars
      prevalent in Iran were sequenced and cloned. RESULTS: PCR amplification of the
      ompL1 gene using the designed primers resulted in a 963 bp ompL1 gene product.
      The PCR based on the ompL1 gene detected all pathogenic reference serovars of
      Leptospira spp. tested. Based on alignment and phylogenetic analysis, although
      the ompL1 nucleotide sequence was slightly different within three vaccinal
      serovars (100%-85% identity), amino acid alignment of the OmpL1 proteins revealed
      that there would be inconsiderable difference among them. CONCLUSION: The ompL1
      gene of the three isolates was well conserved, differing only by a total of 6 bp
      and the proteins by 2 amino acids. The cloned gene could be further used for
      expression and recombinant OmpL1 as an efficient and conserved antigen, and may
      be a useful vaccine candidate against leptospirosis in our region.

PMID- 24916866
TI  - Occurrence of Clostridium difficile infections due to PCR ribotype 027 in
      Bucharest, Romania.
AB  - INTRODUCTION: Little is known about prevailing ribotypes of Clostridium difficile
      infection in Romania where CDI is not a mandatory notifiable disease.
      METHODOLOGY: We studied 64 non-duplicate C. difficile isolates from patients
      hospitalised at the National Institute of Infectious Diseases, Bucharest, Romania
      between March 2011 and March 2012. RESULTS: Sixty-three of the 64 C. difficile
      isolates produced toxins A and B whereas 44 (69%) isolates produced a binary
      toxin. Ribotype 027 accounted for 43 (68%) of the 63 toxigenic strains. The
      remaining 20 isolates belonged to ribotypes 018 (n = 9), 012 (n = 3), and, with
      one isolate each, 014, 031, 081, 416, 433, 500, 507 and PR03035 (new ribotype).
      Information on hospital mortality was available for 62 of the 64 patients; among
      these 62 cases, 4 (6.4%) ended fatal. Recurrence was documented for 11 (18.3%) of
      the 60 patients for whom this information was available. Multilocus variable
      number tandem repeat analysis of the 43 isolates of ribotype 027 yielded a unique
      cluster for the Romanian isolates when compared to Austrian or Italian isolates.
      CONCLUSION: Our findings sustain the hypothesis of a recent emerged outbreak of
      C. difficile PCR ribotype 027 infections in the area of Bucharest.

PMID- 24916867
TI  - Frequency and antibiotic susceptibility patterns of urinary pathogens in male
      outpatients in Argentina.
AB  - INTRODUCTION: Knowledge of the etiology and antimicrobial susceptibility patterns
      of uropathogens is important for determining the best treatment option. This
      study aimed to determine the distribution and antibiotic susceptibility patterns
      of bacterial strains isolated from adult male outpatients. METHODOLOGY: Between
      November 2012 and April 2013, 3,105 community urine samples were analyzed from
      adult male patients who attended the Laboratorio Hidalgo, Buenos Aires,
      Argentina. Antimicrobial susceptibility testing was performed by the Kirby-Bauer
      disc diffusion method. Isolates resistant to third generation cephalosporin were
      tested for extended-spectrum beta-lactamase (ESBL) production using the double
      disk synergy test. RESULTS: Of the 3,105 urine samples analyzed, 791 (25.5%) had
      significant bacteriuria. The frequency of positive urine cultures increased
      significantly with patient age. Escherichia coli was isolated most frequently
      (47.3%), followed by Enterococcus faecalis (13.6%), and Klebsiella pneumoniae
      (11.9%). Gram-negative organisms represented 78.8% of urinary pathogens. The
      highest activities against Gram-negative bacteria were found with imipenem
      (99.0%), amikacin (98.1%), ertapenem (94.2%), fosfomycin (90.7%), and
      piperacillin-tazobactam (90.1%). The frequencies of ESBLs among E. coli, K.
      pneumoniae, and P. mirabilis were 15.2 %, 22.3%, and 8%, respectively.
      Fosfomycin, piperacillin-tazobactam, and nitrofurantoin were most effective
      against Gram-positive organisms. CONCLUSIONS: Fosfomycin may be an excellent
      option for cystitis treatment in patients without risk factors, whereas
      piperacillin-tazobactam is preferred for the treatment of parenchymatous UTIs,
      complicated UTIs, and UTIs associated with risk factors. To ensure the optimal
      selection of antibiotics, physicians should have access to up-to-date information
      about the local prevalence of antimicrobial resistance.

PMID- 24916868
TI  - Antimicrobial resistance, class 1 integrons, and horizontal transfer in
      Salmonella isolated from retail food in Henan, China.
AB  - INTRODUCTION: Salmonellosis remains one of the most frequently occurring
      foodborne diseases worldwide, especially in developing countries. The increasing
      prevalence of multidrug resistance among Salmonella isolates from food has been
      an emerging problem in China. METHODOLOGY: In this study, a total of 638 food
      samples including raw meat, seafood, vegetables, and cooked meat were collected
      in Henan province of China between July 2007 and August 2008 to determine the
      prevalence of Salmonella. These isolates were subjected to serotyping,
      antimicrobial susceptibility, presence of class 1 integrons, and horizontal
      transfer of integrons. RESULTS: The overall percentage of Salmonella prevalence
      was 9.7% (n = 62). Among these isolates, S. Anatum and S. Senftenberg were most
      common, and high rates of antimicrobial resistance were observed to
      sulfamethoxazole (90.3%), trimethoprim/sulfamethoxazole (87.1%), streptomycin
      (29.0%), and ciprofloxacin (25.8%). Class 1 integrons were detected in 16.1% of
      these isolates, and contained gene cassettes dfrA12-aadA2, dfrA1-aadA1, and
      dfrA1. Three Salmonella isolates could transfer their integrons and resistance
      genes to Escherichia coli by conjugation. CONCLUSIONS: Our findings indicate that
      the mobile DNA elements could play an important role in the dissemination of
      resistance determinants among those Salmonella isolates.

PMID- 24916869
TI  - Molecular characterization and antibiotic resistance of Salmonella in children
      with acute gastroenteritis in Abuja, Nigeria.
AB  - INTRODUCTION: In Nigeria, acute gastroenteritis in children under five years of
      age is a major cause of mortality and morbidity; identification and
      characterization of microbial agents of acute gastroenteritis, including
      Salmonella, remains a powerful tool for effective management, surveillance, and
      control. METHODOLOGY: Diarrheal stool samples were directly plated onto
      differential and selective media to isolate Salmonella. Extended-spectrum beta
      lactamases were screened using the double disk diffusion technique and by PCR
      targeting the blaTEM and blaCTX-M genes. Pulsed-field gel electrophoresis (PFGE)
      was performed usingthe PulseNet Canada Laboratory protocol for molecular
      subtyping using the restriction enzymes XbaI and BlnI. RESULTS: The serotypes
      identified were Salmonella enterica serovar Zanzibar (n = 5), Salmonella
      Brancaster (n = 3), and one isolate of Salmonella Enteritidis (phage type 1). The
      following levels of resistance were found among the Salmonella strains:
      amoxicillin, five strains (55.6%); amoxicillin-clavulanic acid, two strains
      (22.2%); cephalexin, five strains (55.6%); and cefuroxime, five strains (55.6%).
      Intermediate resistance was found in five strains (55.6%) only to amoxicillin
      clavulanic acid. All isolates were susceptible to nalidixic acid, ciprofloxacin,
      and ceftriaxone, and no ESBL-producing Salmonella were detected. CONCLUSIONS: Our
      findings demonstrated the involvement of three Salmonella serovars in acute
      gastroenteritis; resistance to penicillins and cephalosporins was common.

PMID- 24916870
TI  - Cholera outbreaks in Malawi in 1998-2012: social and cultural challenges in
      prevention and control.
AB  - INTRODUCTION: Cholera still remains a significant cause of morbidity and
      mortality in developing countries, although comprehensive surveillance data to
      inform policy and strategies are scarce. METHODOLOGY: A desk review of the
      national cholera database and zonal and districts reports was conducted.
      Interviews were conducted with district health management teams, health workers,
      and participants in communities in six districts affected by cholera in 2011/2012
      to obtain data on water, sanitation, and sociocultural issues. RESULTS: From 1998
      to 2012, cholera outbreaks occurred every year in Malawi, with the highest number
      of cases and deaths reported in 2001/2002 (33,546 cases, 968 deaths; case
      fatality rate [CFR] 2.3%). In 2011/2012, cholera outbreak was widespread in the
      southern region, affecting 10 out of 13 districts, where 1,806 cases and 38
      deaths (CFR 2.1%) were reported. Unsafe water sources, lack of maintenance of
      broken boreholes, frequent breakdown of piped water supply, low coverage of pit
      latrines (range 40%-60%), lack of hand washing facilities (< 5%), salty borehole
      water, fishermen staying on Lake Chilwa, cross-border Malawi-Mozambique disease
      spread, and sociocultural issues were some of the causes of the persistent
      cholera outbreaks in Malawi. CONCLUSIONS: Despite improvements in safe drinking
      water and sanitation, cholera is still a major public health problem.
      Introduction of a community-led total sanitation approach, use of social and
      cultural information in community mobilization strategies, and introduction of an
      oral cholera vaccine could help to eliminate cholera in Malawi.

PMID- 24916871
TI  - Isolation of the Bacillus thuringiensis plasmid carrying Bacthuricin F4 coding
      genes and evidence of its conjugative transfer.
AB  - INTRODUCTION: Conjugation is an excellent natural mode of DNA transfer in vivo
      between bacteria, particularly when these conjugative elements carry
      technological traits such as bacteriocin encoding genes. In the present work, the
      bacteriocinogenic plasmid pIBF4 from Bacillus thuringiensis responsible of
      Bacthuricin F4 synthesis was isolated and characterized. METHODOLOGY: To isolate
      pIBF4, the total plasmid DNA from a non-bacteriocin transposant carrying the mini
      Tn10 spectinomycin selective marker was extracted and used to transform
      Escherichia coli strain Top10. PIBF4 was extracted from the obtained transformant
      and then subjected to restriction enzyme analysis. Plasmid curing experiments
      were conducted to test the stability of pIBF4 at a stringent temperature of 42
      degrees C. Conjugative behavior of pIBF4 was assessed by mating experiments using
      the non-bacteriocin transposant mutant as a donor strain and several Bacillus
      thuringiensis strains as recipients. RESULTS: The pIBF4 plasmid was isolated and
      had a molecular weight of 19.1 kb. Ninety-five percent of cells retained the
      pIBF4 plasmid after 200 generations, demonstrating its high stability. PIBF4 was
      successfully transferred to Bacillus thuringiensis HD1CryB strain with a transfer
      frequency of 1x10(-8) transconjugants per donor cell. The study of the recipient
      host range revealed that pIBF4 is specifically transferable to Bacillus
      thuringiensis strains with variable transfer frequencies depending on the
      recipient host strain. CONCLUSION: Our results show that pIBF4 is a 19.1 kb
      highly stable plasmid transferable by conjugation to Bacillus thuringiensis
      strains with deferent transfer frequencies.

PMID- 24916872
TI  - Molecular surveillance of Dengue in Sukabumi, West Java province, Indonesia.
AB  - INTRODUCTION: Dengue is endemic and affects people in all Indonesian provinces.
      Increasing dengue cases have been observed every year in Sukabumi in West Java
      province. Despite the endemicity, limited data is available on the genetic of
      dengue viruses (DENV) circulating in the country. To understand the dynamics of
      dengue disease, we performed molecular and serological surveillance of dengue in
      Sukabumi. METHODOLOGY: A total of 113 patients were recruited for this study.
      Serological data were obtained using anti-dengue IgM and IgG tests plus dengue
      NS1 antigen detection. Dengue detection and serotyping were performed using real
      time RT-PCR. Viruses were isolated and the envelope genes were sequenced.
      Phylogenetic and evolutionary analyses were performed to determine the genotype
      of the viruses and their evolutionary rates. RESULTS: Real-time RT-PCR detected
      DENV in 25 (22%) of 113 samples. Serotyping revealed the predominance of DENV-2
      (16 isolates, 64%), followed by DENV-1 (5 isolates, 20%), and DENV-4 (4 isolates,
      16%). No DENV-3 was detected in the samples. Co-circulation of genotype I and IV
      of DENV-1 was observed. The DENV-2 isolates all belonged to the Cosmopolitan
      genotype, while DENV-4 isolates were grouped into genotype II. Overall, their
      evolutionary rates were similar to DENV from other countries. CONCLUSIONS: We
      revealed the distribution of DENV serotypes and genotypes in Sukabumi. Compared
      to data obtained from other cities in Indonesia, we observed the differing
      predominance of DENV serotypes but similar genotype distribution, where the
      infecting viruses were closely related with Indonesian endemic viruses isolated
      previously.

PMID- 24916873
TI  - Quantifying the mortality caused by the H1N1 influenza virus during the 2009
      pandemic in Mexico.
AB  - INTRODUCTION: The frequency and mortality of the pandemic caused by influenza
      A(H1N1)pdm09 might have been underestimated, especially in developing countries.
      This study was designed to quantify the possible underestimation of pandemic
      influenza mortality and evaluate the concordance between the data reported for
      A(H1N1)pdm09 mortality and the causes of death reported during the pandemic
      period of April 2009 to February 2010. METHODOLOGY: The death certificates of 754
      confirmed cases of A(H1N1)pdm09 infection were included in the study. Data was
      analyzed using the United States Centers for Disease Control and Prevention's
      statistical model accounts for the variability in the proportion at each step
      using the Monte Carlo probabilistic model sampled from a uniform probability
      distribution. RESULTS: A total of 1,969 deaths were estimated, with an estimated
      lethality of 5.53 per 100,000 (range, 3.5-8.76 per 100,000) in contrast with the
      754 deaths and a lethality of 1.98 per 100,000 infected patients officially
      reported. In 631 of 754 (83.7%) death certificates from A(H1N1)pdm09 influenza
      positive patients, influenza was not mentioned as a cause of death. CONCLUSIONS:
      It is possible that the mortality of the pandemic was three times higher than
      officially reported in Mexico. One source of error that could explain this
      underestimation is in the completion of death certificates, because in > 80% of
      confirmed cases of infection with influenza virus, it was not reported as the
      cause of death.

PMID- 24916874
TI  - Crimean-Congo hemorrhagic fever and its relationship with climate factors in
      southeast Iran: a 13-year experience.
AB  - INTRODUCTION: Crimean-Congo hemorrhagic fever (CCHF) is endemic in southeast
      Iran. In this study we present the epidemiological features of CCHF and its
      relationship with climate factors in over a 13-year span. METHODOLOGY:
      Surveillance system data of CCHF from 2000 to 2012 were obtained from the
      Province Health Centre of Zahedan University of Medical Sciences in southeast
      Iran. The climate data were obtained from the climate organization. The seasonal
      auto-regression integrated moving average (SARIMA) model was used for time series
      analysis to produce a model as applicable as possible in predicting the
      variations in the occurrence of the disease. RESULTS: Between 2000 and 2012, 647
      confirmed CCHF cases were reported from Sistan-va-Baluchistan province. The total
      case fatality rate was about 10.0%. Climate variables including mean temperature
      ( degrees C), accumulated rainfall (mm), and maximum relative humidity (%) were
      significantly correlated with monthly incidence of CCHF (p <0.05). There was no
      clear pattern of decline in the reported number of cases within the study's time
      span. The first spike in the number of CCHF cases in Iran occurred after the
      first surge of the disease in Pakistan. CONCLUSIONS: This study shows the
      potential of climate indicators as predictive factors in modeling the occurrence
      of CCHF, even though it has to be appreciated whether there is any need for a
      practically applicable model. There are also other factors, such as entomological
      indicators and virological finding that must be considered.

PMID- 24916875
TI  - Detection and gB genotyping of CMV in Mexican preterm infants in the context of
      maternal seropositivity.
AB  - INTRODUCTION: Congenital (CI) and perinatal cytomegalovirus (CMV) infections (PI)
      can be linked to maternal CMV seropositivity, with fatal consequences in preterm
      newborns. GB genotyping has been used to analyze genotypic similarity in mothers
      and infants. The frequency of CMV infection in the context of maternal
      seropositivity and the viral gB genotypes as well as the genotypic similarity in
      mothers and preterm infants were investigated. METHODOLOGY: Saliva samples and
      dry blood spots (DBS) were taken weekly from preterm newborns  from birth until
      the first month of life, and breast milk samples were taken from their mothers
      weekly during the first month of lactation. CMV IgG seroprevalence of the mothers
      and CI or PI in the infants were established. The gB status and genotypic
      similarities were established retrospectively in DBS and in the breast milk
      samples. RESULTS: In total, 387 neonates and 375 mothers were enrolled. The
      maternal CMV-positive IgG serology was 97.3% (365/375). Neonatal CMV was found in
      5.1% (20/387) of newborns, and one infant presented with CMV-compatible symptoms.
      CI was 2.5% and PI in the first month after birth was 11.8%. GB2 was the most
      prevalent genotype and was also the genotype preferentially transmitted to
      newborns by mothers with mixed infections. CONCLUSIONS: CMV PI and CI in preterm
      infants from highly seropositive mothers was high, but the rate of symptomatic
      infection was low. The prevalent genotype was gB2, and this genotype was
      preferentially transmitted to newborns by mothers with mixed infections.

PMID- 24916876
TI  - Pfcrt mutant haplotypes may not correspond with chloroquine resistance.
AB  - INTRODUCTION: Chloroquine resistance in Plasmodium falciparum is associated with
      mutations in pfcrt and pfmdr1 genes. The frequency distribution of pfcrt K76T and
      pfmdr1 N86Y mutations and their association with chloroquine susceptibility was
      studied in an endemic area along the Indo-Bangladesh border. METHODOLOGY: A
      single-arm prospective study of clinical and parasitological responses in P.
      falciparum malaria patients to chloroquine was conducted in vivo. PCR-RFLP assay
      was used to detect pfcrt K76T and pfmdr1 N86Y mutations in P. falciparum. The PCR
      products of pfcrt gene were sequenced,  translated and aligned for haplotyping.
      RESULTS: Out of 63 cases, 44 (69.8%) responded adequately to chloroquine
      treatment. Pfcrt K76T mutation was recorded in 100% of the treatment failure
      cases, whereas pfmdr1 N86Y mutation was found in 52.6% of the cases only. Early
      treatment failure (84.2%) occurred more frequently than late treatment failure
      (15.8%). Kaplan-Meier survival analysis showed that the probability estimate for
      treatment success after 7 and 15 days was 0.84 (95% CI = 0.72-0.92) and 0.70 (95%
      CI = 0.57-0.80), respectively. Sequence analysis of 72 to 76 pfcrt gene codons
      revealed the presence of two mutant (CVMNT, CVIET) and two wild (CVMNK, CVIEK)
      haplotypes. The mutant CVIET haplotype was predominantly distributed (42.1%).
      CONCLUSIONS: The presence of mutations in pfcrt K76T and pfmdr1 N86Y genes is not
      sufficient to explain the therapeutic efficacy of chloroquine to P. falciparum.
      Study suggests that pfcrt K76T mutant haplotypes are widely distributed and are
      spreading diligently, which needs to be taken into account in devising an
      antimalarial policy.

PMID- 24916877
TI  - Occurrence of extended-spectrum beta-lactamases in human and bovine isolates of
      Escherichia coli from Oyo state, Nigeria.
AB  - INTRODUCTION: The main objective of the study was the molecular characterization
      of extended spectrum beta-lactamases (ESBL) in Escherichia coli isolates
      collected from human and bovine samples in Oyo state, Nigeria. METHODOLOGY:
      Between August 2010-2011, 114 E. coli isolates were collected from hospitals (n =
      57) and bovine (n = 57). PCR and sequencing were used for identification of
      ESBLs, upstream sequences, plasmid-mediated quinolone resistance (PMQR) genes and
      class 1 integrons. Plasmid incompatibility groups were identified among ESBL
      positive isolates by PCR. Genetic relatdness was assessed by rep-PCR and MLST.
      Transfer of ESBL determinants to the recipient strain E. coli J53 was performed
      by broth mating assays. RESULTS: CTX-M15 was the unique ESBL found in eight human
      isolates. Six CTX-M-15 producers also carry the aac(6')-lb-cr gene and/or qnrB
      gene, and class 1 integrons. FIA, FIB, H11, H12, F, Y and K were the plasmid
      replicon types found. CTX-M-15 and PMQR determinants were transferred by
      conjugation in two E. coli assigned by MLST to ST131 and ST2695, a new allele.
      CONCLUSIONS: The study highlights the dissemination hability of CTX-M-15
      associated with PMQR, and the presence of class 1 integrons, able to capture
      additional genes, justifying the urgent need of antimicrobial resistance
      surveillance in Nigeria.

PMID- 24916878
TI  - Understanding of antibiotic use and resistance among final-year pharmacy and
      medical students: a pilot study.
AB  - INTRODUCTION: This study is aimed to investigate the understanding of antibiotic
      use and antibiotic resistance and its correlate factors among final-year medical
      and pharmacy students at International Islamic University Malaysia (IIUM).
      METHODOLOGY: This was a cross-sectional study. The study instrument was developed
      by extensive literature search and was subjected to face validity and content
      validity to medical and pharmacy academics. A pilot study was conducted to
      ascertain the reliability coefficient. Data was entered to SPSS version 17 and
      descriptive and inferential statistics were applied. RESULTS: A total of 123
      questionnaires were included in the study. Out of 123 respondents, 58.5% (n = 72)
      were final-year medical students, while 41.5% (n = 51) were final-year pharmacy
      students. The majority of the respondents showed adequate knowledge regarding the
      course contents related to antibiotics (n = 116; 94.3%). Almost all the
      respondents correctly reported the difference between bactericidal and
      bacteriostatic antibiotics. Only 15.4% (n = 19) and 27.6% (n = 34) of students
      were able to recognize Streptococcus pyogenes as non-pencillin resistant
      bacterium and Enterococcus as vancomycin-resistant bacterium, respectively.
      CONCLUSIONS: The students showed good understanding regarding antibiotic
      resistance. In comparison to medical students, pharmacy students showed better
      understanding and more adequate knowledge, as the mean value for each domain was
      slightly higher for pharmacy students. Extensively improving the curriculum and
      educating healthcare professionals, especially physicians and pharmacists, right
      from the time of their educational training can inculcate a moral responsibility
      toward the judicious use of antibiotics, which can serve to eradicate antibiotic
      resistance.

PMID- 24916880
TI  - First report of Chikungunya virus infection in Nepal.
AB  - Chikungunya virus is an emerging arboviral disease that has been spreading
      rapidly across south Asia in recent years. Until recently, no chikungunya cases
      have been reported in Nepal. For the first time, we report three cases of
      chikungunya virus infection in Nepal. 

PMID- 24916879
TI  - Intestinal parasites in children hospitalized at the Central Hospital in Maputo,
      Mozambique.
AB  - INTRODUCTION: Intestinal parasites are important contributors to the global
      disease burden, especially in children of low-income countries. The present study
      determined the frequency of intestinal parasites in children hospitalized at the
      diarrhea section of the Infectious-Contagious Diseases ward and at the
      Malnutrition ward of the Department of Pediatrics of the Maputo Central Hospital
      in Mozambique. METHODOLOGY: This pilot study conducted between February and March
      2009 enrolled a total of 93 children between 1.5 and 48.2 months of age; 87.1%
      were younger than 24 months. Parasite detection in stool samples was achieved
      using direct microscopic observation and Ritchie's concentration technique.
      RESULTS: Infection with pathogenic intestinal parasites was detected in 16.1%
      (15/93) of the children. Giardia duodenalis and Trichuris trichiura were the most
      common parasites (6.5%, 6/93 each), followed by Ascaris lumbricoides (2.2%,
      2/93). One case of mixed infection with A. lumbricoides plus T. trichiura was
      also detected. CONCLUSION: This study reinforces the importance of routinely
      examining stool samples for the diagnosis of intestinal parasites (including
      protozoa) in children hospitalized in endemic areas.

PMID- 24916881
TI  - Bloodstream infection with Oligella ureolytica in a newborn infant: a case report
      and review of the literature.
AB  - Oligella species are small, Gram-negative, nonsaccharolytic aerobic rods or
      coccobacilli that are catalase and oxidase-positive, mostly isolated from the
      urinary tract and rarely from wounds, bloodstream infections, septic arthritis,
      or peritonitis.In this article, we report a case of O.ureolytica-related
      bloodstream infection in a newborn infant and we review the literature for
      previously reported cases of Oligella infections. 

PMID- 24916882
TI  - Frequency of mutations in the rpoB gene of multidrug-resistant Mycobacterium
      tuberculosis clinical isolates from Sudan.

PMID- 24916883
TI  - Bleeding complications in dengue are not associated with significant changes in
      the modulators of the endothelial barrier.
AB  - Bleeding complications in dengue may occur irrespective of the presence of plasma
      leakage. We compared plasma levels of modulators of the endothelial barrier among
      three dengue groups: bleedings without plasma leakage, dengue hemorrhagic fever,
      and non-complicated dengue. The aim was to evaluate whether the presence of
      subtle alterations in microvascular permeability could be detected in bleeding
      patients. Plasma levels of VEGF-A and its soluble receptors were not associated
      with the occurrence of bleeding in patients without plasma leakage. These results
      provide additional rationale for considering bleeding as a complication
      independent of endothelial barrier breakdown, as proposed by the 2009 WHO
      classification. 

PMID- 24916884
TI  - Influence of resistance exercise intensity and metabolic stress on anabolic
      signaling and expression of myogenic genes in skeletal muscle.
AB  - INTRODUCTION: We investigated the effect of resistance exercise intensity and
      exercise-induced metabolic stress on the activation of anabolic signaling and
      expression of myogenic genes in skeletal muscle. METHODS: Ten strength-trained
      athletes performed high-intensity [HI, 74% of 1-repetition maximum (RM)], middle
      intensity (MI, 54% 1RM), or middle-intensity (54% 1RM) no-relaxation exercise
      (MIR). Kinase phosphorylation level and myogenic gene expression in muscle
      samples were evaluated before, 45 min, 5 h, and 20 h after exercise. RESULTS: The
      lactate concentration in MI was approximately 2-fold lower than in the 2 other
      sessions, and was highest in MIR. The phosphorylation level of extracellular
      kinase 1/2Thr202/Tyr204 after exercise was related to metabolic stress. Metabolic
      stress induced a decrease in myostatin mRNA expression, whereas mechano-growth
      factor mRNA level depended on exercise intensity. CONCLUSIONS: This study
      demonstrates that both intensity and exercise-induced metabolic stress can be
      manipulated to affect muscle anabolic signaling.

PMID- 24916885
TI  - Engineered thermostable fungal cellulases exhibit efficient synergistic cellulose
      hydrolysis at elevated temperatures.
AB  - A major obstacle to using widely available and low-cost lignocellulosic
      feedstocks to produce renewable fuels and chemicals is the high cost and low
      efficiency of the enzyme mixtures used to hydrolyze cellulose to fermentable
      sugars. One possible solution entails engineering current cellulases to function
      efficiently at elevated temperatures in order to boost reaction rates and exploit
      several other advantages of a higher temperature process. Here, we describe the
      creation of the most stable reported fungal endoglucanase, a derivative of
      Hypocrea jecorina (anamorph Trichoderma reesei) Cel5A, by combining stabilizing
      mutations identified using consensus design, chimera studies, and structure-based
      computational methods. The engineered endoglucanase has an optimal temperature
      that is 17 degrees C higher than wild type H. jecorina Cel5A, and hydrolyzes 1.5
      times as much cellulose over 60 h at its optimum temperature compared to the wild
      type enzyme at its optimal temperature. This enzyme complements previously
      engineered highly active, thermostable variants of the fungal cellobiohydrolases
      Cel6A and Cel7A in a thermostable cellulase mixture that hydrolyzes cellulose
      synergistically at an optimum temperature of 70 degrees C over 60 h.The
      thermostable mixture produces three times as much total sugar as the best mixture
      of the wild type enzymes operating at its optimum temperature of 60 degrees C,
      clearly demonstrating the advantage of higher temperature cellulose hydrolysis.

PMID- 24916886
TI  - Cutting-edge discussions of management, policy, and program issues in emergency
      care.

PMID- 24916887
TI  - Directing peptide crystallization through curvature control of nanotubes.
AB  - In the absence of efficient crystallization methods, the molecular structures of
      fibrous assemblies have so far remained rather elusive. In this paper, we present
      a rational method to crystallize the lanreotide octapeptide by modification of a
      residue involved in a close contact. Indeed, we show that it is possible to
      modify the curvature of the lanreotide nanotubes and hence their diameter. This
      fine tuning leads to crystallization because the radius of curvature of the
      initially bidimensional peptide wall can be increased up to a point where the
      wall is essentially flat and a crystal is allowed to grow along a third
      dimension. By comparing X-ray diffraction data and Fourier transform Raman
      spectra, we show that the nanotubes and the crystals share similar cell
      parameters and molecular conformations, proving that there is indeed a structural
      continuum between these two morphologies. These results illustrate a novel
      approach to crystallization and represent the first step towards the acquisition
      of an A-resolution structure of the lanreotide nanotubes beta-sheet assembly.

PMID- 24916888
TI  - Phlorins bearing different substituents at the sp3-hybridized meso-position.
AB  - Phlorins bearing different substituents at the sp(3)-hybridized meso-position
      were investigated. The extent to which different substituents at this unique
      position can influence phlorin spectroscopic properties, structure, and stability
      is of interest given that such substituents are not in direct conjugation with
      the phlorin macrocycle. While the effect of various substituents at the sp(2)
      hybridized positions has been the subject of prior investigations, the impact of
      different substituents at the saturated carbon atom has not been systematically
      examined. In this study, phlorins with different combinations of geminal methyl
      and phenyl substituents were prepared in yields of 24-49% via dipyrromethane +
      dipyrromethanedicarbinol routes, and their NMR spectra, UV-vis spectra, X-ray
      crystal structures, and stability toward light and air were compared. The nature
      of the substituents at the sp(3)-hybridized position was found to impact
      spectroscopic properties, structure, and stability to varying degrees. Thus, the
      choice of substituents at the sp(3)-hybridized meso-position provides a further
      option for altering phlorin properties. 

PMID- 24916889
TI  - Dental trauma: prevalence and risk factors in schoolchildren.
AB  - OBJECTIVES: This cross-sectional study aimed to determine the prevalence of
      traumatic injury to the permanent incisors in 8- to 12-year-old children and to
      test associations between dental trauma and nutritional status and physical
      activity level, with adjustment for demographic, behavioral, and psychosocial
      variables. Differences in risk factors between sexes were also assessed. METHODS:
      Two-stage cluster sampling was used to select 1210 children in 20 public and
      private schools in Pelotas, Brazil, for study participation. Dental trauma was
      assessed using the O'Brien criteria. Parents provided information about
      socioeconomic characteristics and their children's history of trauma in early
      childhood via questionnaire. Children were interviewed to obtain demographic and
      psychosocial information and to assess physical activity level. Anthropometric
      measures were collected for body mass index calculation. Hierarchical Poisson
      regression was used for data analyses. RESULTS: The prevalence of dental trauma
      was 12.6% [95% confidence interval (CI), 10.8-14.7%] in the entire sample; it
      increased with age from 7.2% at 8 years to 21.5% at 12 years. In the adjusted
      analysis, dental trauma was more prevalent in boys [prevalence ratio (PR) = 0.71;
      95% CI, 0.50-0.99], older children (PR = 3.57; 95% CI, 1.73-7.34), those with
      inadequate lip coverage (PR = 2.03; 95% CI, 1.22-3.38), and those with histories
      of trauma in the primary dentition (PR = 2.60; 95% CI, 1.80-3.75). In a sex
      stratified analysis, dental trauma was more prevalent in overweight/obese boys
      (PR = 1.65; 95% CI, 1.10-2.92). No significant association was found with
      socioeconomic variables, psychosocial characteristics, physical activity level,
      or school retention among boys or girls. CONCLUSIONS: The pronounced increase in
      the prevalence of dental trauma with age highlights the need to establish
      preventive strategies among schoolchildren. The risk of dental injury was
      increased in overweight/obese boys and children with histories of dental trauma
      in early childhood, confirming the existence of accident-prone children.

PMID- 24916890
TI  - A prognostic classifier consisting of 17 circulating cytokines is a novel
      predictor of overall survival for metastatic colorectal cancer patients.
AB  - We aimed to determine the prognostic values of 39 circulating cytokines in
      Chinese patients with metastatic colorectal cancer (CRC) and to develop a novel
      cytokine-based prognostic classifier (CBPC) for prognostic prediction. A total of
      176 patients were divided into two cohorts based on the date of first-line
      chemotherapy. The first 99 cases were assigned to the training cohort, and the
      remaining 77 cases were assigned to the validation cohort. Thirty-nine cytokines
      were simultaneously analyzed in the patient serum samples using multiplex bead
      based Luminex technology. We used support vector machine-based methods and Cox
      proportional hazards models to develop a CBPC from the training cohort, which we
      then validated using the second patient cohort. Univariate analysis showed that
      FGF-2, TGFalpha, Flt-3L, GM-CSF, INFalpha2, GRO, IL-10, MCP-3, MDC, sIL-2Ralpha,
      IL-2, IL-7, IL-8, MCP-1, MIP-1beta, TNFalpha and VEGF were significant risk
      factors affecting the overall survival (OS) of both the training cohort and the
      validation cohort. We developed a CBPC to predict the OS of metastatic CRC
      patients using these 17 cytokines (sensitivity, 0.835; specificity, 0.800). In
      the validation cohort, the CBPC was found to have significant power in predicting
      the OS of metastatic CRC patients. Our study showed that there were significant
      associations between cytokine expression and prognosis of the patients with
      metastatic CRC. The CBPC that we developed includes multiple circulating
      cytokines and may serve as a novel screening tool for identifying metastatic CRC
      patients with a high risk of short OS. These high-risk individuals may also be
      suitable for cytokine-targeted therapies. 

PMID- 24916891
TI  - Does the CONSORT checklist for abstracts improve the quality of reports of
      randomized controlled trials on clinical pathways?
AB  - RATIONALE AIMS AND OBJECTIVES: The extension of the Consolidated Standards of
      Reporting Trials (CONSORT) statement provides reporting guidelines to improve the
      reporting quality of randomized controlled trials (RCTs). This present study was
      aim to assess the reporting quality of abstracts of RCTs on clinical pathway.
      METHODS: Eight databases were searched from inception to November 2012 to
      identify RCTs. We extracted basic information and CONSORT items from abstracts.
      Each abstract was assessed independently by two reviewers. Statistical analyses
      were performed with SPSS 13.0. Level of significance was set at P < 0.05.
      RESULTS: 328 abstracts were included. 300 (91.5%) were published in Chinese, of
      which 292 were published on high impact factor journals. 28 English abstracts
      were all published on Science Citation Index (SCI) journals. (1) Intervention,
      objective and outcome were almost fully reported in all abstracts, while
      recruitment and funding were never reported. (2) There are nine items (P < 0.05)
      in Chinese that were of low quality compared with in English. There was
      statistically difference on total score between Chinese and English abstracts (P
      < 0.00001). (3) There was no difference in any items between high and low impact
      factor journal in China. (4) In SCI journals, there were significant changes in
      reporting for three items trial design (P = 0.026), harms (P = 0.039) and trial
      registration (P = 0.019) in different periods (pre- and post-CONSORT), but only
      the numbers of randomized (P = 0.003) changed in Chinese abstracts. CONCLUSIONS:
      The reporting quality of abstracts of RCTs on clinical pathway still should be
      improved. After the publication of CONSORT for abstracts guideline, the RCT
      abstracts reporting quality were improvement to some extent. The abstracts in
      Chinese journals showed non-adherence to the CONSORT for abstracts guidelines.

PMID- 24916893
TI  - Habiterpenol, a novel abrogator of bleomycin-induced G2 arrest in Jurkat cells,
      produced by Phytohabitans suffuscus 3787_5.
AB  - A small molecule named habiterpenol produced by actinomycete Phytohabitans
      suffuscus 3787_5 was found to abrogate bleomycin-induced G2 arrest in Jurkat
      cells. Habiterpenol showed no cytotoxic effect on Jurkat cells even at 273 MUM;
      however, the compound inhibited bleomycin-induced G2 arrest in Jurkat cells with
      an IC50 value of 3.55 MUM, while it showed no effect on colchicine-induced M
      arrest even at 273 MUM. These results indicated that habiterpenol selectively
      abrogated bleomycin-induced G2 arrest in Jurkat cells. 

PMID- 24916892
TI  - Development of the Migrant Friendly Maternity Care Questionnaire (MFMCQ) for
      migrants to Western societies: an international Delphi consensus process.
AB  - BACKGROUND: Through the World Health Assembly Resolution, 'Health of Migrants',
      the international community has identified migrant health as a priority.
      Recommendations for general hospital care for international migrants in receiving
      countries have been put forward by the Migrant Friendly Hospital Initiative;
      adaptations of these recommendations specific to maternity care have yet to be
      elucidated and validated. We aimed to develop a questionnaire measuring migrant
      friendly maternity care (MFMC) which could be used in a range of maternity care
      settings and countries. METHODS: This study was conducted in four stages. First,
      questions related to migrant friendly maternity care were identified from
      existing questionnaires including the Migrant Friendliness Quality Questionnaire,
      developed in Europe to capture recommended general hospital care for migrants,
      and the Mothers In a New Country (MINC) Questionnaire, developed in Australia and
      revised for use in Canada to capture the maternity care experiences of migrant
      women, and combined to create an initial MFMC questionnaire. Second, a Delphi
      consensus process in three rounds with a panel of 89 experts in perinatal health
      and migration from 17 countries was undertaken to identify priority themes and
      questions as well as to clarify wording and format. Third, the draft
      questionnaire was translated from English to French and Spanish and back
      translated and subsequently culturally validated (assessed for cultural
      appropriateness) by migrant women. Fourth, the questionnaire was piloted with
      migrant women who had recently given birth in Montreal, Canada. RESULTS: A 112
      item questionnaire on maternity care from pregnancy, through labour and birth, to
      postpartum care, and including items on maternal socio-demographic, migration and
      obstetrical characteristics, and perceptions of care, has been created--the
      Migrant Friendly Maternity Care Questionnaire (MFMCQ)--in three languages
      (English, French and Spanish). It is completed in 45 minutes via interview
      administration several months post-birth. CONCLUSIONS: A 4-stage process of
      questionnaire development with international experts in migrant reproductive
      health and research resulted in the MFMCQ, a questionnaire measuring key aspects
      of migrant-sensitive maternity care. The MFMCQ is available for further
      translation and use to examine and compare care and perceptions of care within
      and across countries, and by key socio-demographic, migration, and obstetrical
      characteristics of migrant women.

PMID- 24916894
TI  - Structure elucidation of meroterpenoid habiterpenol, a novel abrogator of
      bleomycin-induced G2 arrest in Jurkat cells, produced by Phytohabitans suffuscus
      3787_5.
AB  - A novel abrogator of bleomycin-induced G2 arrest in Jurkat cells, habiterpenol
      (1), was isolated from the culture broth of Phytohabitans suffuscus 3787_5. The
      planar structure of 1 was elucidated by spectroscopic study (1D and 2D NMR, MS,
      UV and IR), and the relative stereochemistry was elucidated by ROESY experiments.
      Compound 1 belongs to a pentacyclic meroterpenoid having a labdan-type diterpene
      connecting to an indane moiety. 

PMID- 24916895
TI  - The ATP synthase inhibitor bedaquiline interferes with small-molecule efflux in
      Mycobacterium smegmatis.

PMID- 24916896
TI  - Prenatal diagnosis and epidemiology of multicystic kidney dysplasia in Europe.
AB  - OBJECTIVES: The aim of this study is to describe the prenatal diagnosis and
      epidemiology of multicystic kidney dysplasia (MCKD). METHODS: The study is based
      on routinely collected data from a European database of major congenital
      anomalies including 13 registries with cases born in 1997-2006 and covering 1 458
      552 births. RESULTS: There were 601 MCKD cases giving an overall prevalence of
      4.12 per 10 000 births with regional variation. In live births, 87% of cases had
      an isolated renal anomaly and 13% had associated major nonrenal anomalies
      (chromosomal, syndrome or other major anomalies). For the cases with isolated
      renal anomalies, 51/386 (11%) and 7/386 (2%) choose to terminate the pregnancy or
      resulted in an intrauterine fetal death, respectively. The prenatal detection
      rate was 88% in both unilateral and bilateral cases. Birth outcome differed with
      92% of unilateral MCKD cases being liveborn compared with 33% of bilateral MCKD
      cases. For unilateral MCKD cases, 84% had an isolated renal anomaly compared with
      51% of bilateral MCKD cases (p < 0.001). CONCLUSIONS: Cases with unilateral MCKD
      are mainly liveborn, and only 16% have associated major malformations or a
      syndrome. Cases with bilateral MCKD are often associated with nonrenal major
      congenital anomalies or part of a syndrome, and only one third of bilateral MCKD
      cases in this study were liveborn. Prenatal detection rate of MCKD was high for
      both unilateral and bilateral cases. (c) 2014 John Wiley & Sons, Ltd.

PMID- 24916897
TI  - Preoperative virtual screening examination of the airway.
AB  - A case of a preoperative airway examination performed using telemedicine is
      presented. The use of this technology has the ability to provide crucial
      information regarding the feasibility of office-based anesthesia in advance and
      limit schedule interruptions on the day of surgery. 

PMID- 24916898
TI  - SEDASYS, sedation, and the unknown.

PMID- 24916899
TI  - In vitro glucuronidation of Armillarisin A: UDP-glucuronosyltransferase 1A9 acts
      as a major contributor and significant species differences.
AB  - 1. This study is performed to investigate liver microsomal glucuronidation of
      Armillarisin A (A.A), an effective cholagogue drug, aiming at characterizing the
      involved UDP-glucuronosyltranferases (UGT) and revealing potential species
      differences. 2. A.A glucuronidation in human liver microsomes (HLM) generates one
      metabolite (M2) glucuronidated at the phenol hydroxyl group, obeying Michaelis
      Menten kinetic model. Multiple isoforms including UGT1A1, 1A7, 1A9 and 2B15 can
      catalyze A.A glucuronidation. Kinetic assays and chemical inhibition studies both
      demonstrate that UGT1A9 is responsible for A.A glucuronidation in HLM. A.A
      glucuronidation in Cynomolgus monkey microsomes (CyLM) also follows Michaelis
      Menten model, but can additionally catalyze the traced glucuronosyl substitution
      at the alcohol hydroxyl group (M1). The reactions in liver microsomes from
      Sprague-Dawley rats (RLM), ICR/CD-1 mouse (MLM), Beagle dog (DLM) all display
      biphasic kinetics and only M2 is detected. HLM, RLM and CyLM exhibit very similar
      catalytic activities towards A.A glucuronidation, with the intrinsic clearance
      values of respective 38, 37 and 37 MUL/min/mg, which are much higher than MLM and
      DLM. 3. This in vitro study indicates that UGT1A9 acts as a major contributor to
      A.A glucuronidation in human liver, and the reaction displays large species
      differences.

PMID- 24916900
TI  - Absorption, distribution, metabolism and excretion of loxoprofen after dermal
      application of loxoprofen gel to rats.
AB  - 1. Loxoprofen (LX), is a prodrug of the pharmacologically active form, trans
      alcohol metabolite (trans-OH form), which shows very potent analgesic effect. In
      this study, the pharmacokinetics and metabolism of [(14)C]LX-derived
      radioactivity after dermal application of [(14)C]LX gel (LX-G) to rats were
      evaluated. 2. The area under concentration-time curve (AUC0-infinity) of
      radioactivity in the plasma after the dermal application was 13.6% of that of the
      oral administration (p < 0.05). 3. After the dermal application, the
      radioactivity remained in the skin and skeletal muscle at the treated site for
      168 h, whereas the AUC0-168 h of the radioactivity concentration in every tissue
      examined except the treated site was statistically lower than that after the oral
      administration (p < 0.05). 4. The trans-OH form was observed at high levels in
      the treated skin site at 0.5 h. Metabolite profiles in plasma, non-treated skin
      site and urine after the dermal application were comparable with those after the
      oral administration. 5. Renal excretion was the main route of elimination after
      the dermal application. 6. In conclusion, compared to the oral administration,
      the dermal application of [(14)C]LX-G showed lower systemic and tissue exposure
      with higher exposure in the therapeutic target site. The radioactivity revealed
      similar metabolite profiles in both administration routes.

PMID- 24916901
TI  - Development of pressurized liquid extraction and solid-phase microextraction
      combined with gas chromatography and flame photometric detection for the
      determination of organophosphate esters in sediments.
AB  - Organophosphate esters have been extensively used as flame retardants and
      plasticizers. The analysis of organophosphate esters in the environment is a hot
      topic because many of them are toxic and persistent. We developed a novel
      procedure for determining organophosphate esters in sediment. In this work,
      pressurized liquid extraction and solid-phase microextraction are used for sample
      preparation to extract and concentrate the analytes, which are then analyzed by
      gas chromatography with flame photometric detection. The extraction parameters of
      pressurized liquid extraction were investigated and optimized by orthogonal
      design and then evaluated by range analysis and analysis of variance. Under the
      optimal conditions, the proposed procedure showed wide linear ranges (0.90-100
      ng/g) with correlation coefficients ranging from 0.9921 to 0.9990. The detection
      limits of the method were in the range of 0.009-0.280 ng/g with standard
      deviations ranging from 2.2 to 9.5%. Recoveries of the proposed method ranged
      from 82.3 to 108.9% with relative standard deviations <8.4%. The obtained method
      was applied successfully to the determination of organophosphate esters in real
      sediments with recoveries varying from 79.8 to 107.3%. The proposed method was
      proved to be simple, easy, and sensitive for analyzing organophosphate esters in
      sediment samples. 

PMID- 24916904
TI  - Letter by Dai et al regarding article, "Targeting recombinant tissue-type
      plasminogen activator in acute ischemic stroke based on risk of intracranial
      hemorrhage or poor functional outcome: an analysis of the Third International
      Stroke Trial".

PMID- 24916903
TI  - Neuronal production of lipocalin-2 as a help-me signal for glial activation.
AB  - BACKGROUND AND PURPOSE: We explored the hypothesis that injured neurons release
      lipocalin-2 as a help me signal. METHODS: In vivo lipocalin-2 responses were
      assessed in rat focal cerebral ischemia and human stroke brain samples using a
      combination of ELISA and immunostaining. In vitro, microglia and astrocytes were
      exposed to lipocalin-2, and various markers and assays of glial activation were
      quantified. Functional relevance of neuron-to-glia lipocalin-2 signaling was
      examined by transferring conditioned media from lipocalin-2-activated microglia
      and astrocytes onto neurons to see whether activated glia could protect neurons
      against oxygen-glucose deprivation and promote neuroplasticity. RESULTS: In human
      stroke samples and rat cerebral ischemia, neuronal expression of lipocalin-2 was
      significantly increased. In primary cell cultures, exposing microglia and
      astrocytes to lipocalin-2 resulted in glial activation. In microglia, lipocalin-2
      converted resting ramified shapes into a long-rod morphology with reduced
      branching, increased interleukin-10 release, and enhanced phagocytosis. In
      astrocytes, lipocalin-2 upregulated glial fibrillary acid protein, brain-derived
      neurotropic factor, and thrombospondin-1. Conditioned media from lipocalin-2
      treated astrocytes upregulated synaptotagmin, and conditioned media from
      lipocalin-2-treated microglia upregulated synaptophysin and post-synaptic density
      95 (PSD95) and protected neurons against oxygen-glucose deprivation. CONCLUSIONS:
      These findings provide proof of concept that lipocalin-2 is released by injured
      neurons as a help me distress signal that activates microglia and astrocytes into
      potentially prorecovery phenotypes.

PMID- 24916905
TI  - Letter by Kawada regarding article, "Sleep duration and risk of stroke mortality
      among Chinese adults: Singapore Chinese Health Study".

PMID- 24916906
TI  - Six-minute magnetic resonance imaging protocol for evaluation of acute ischemic
      stroke: pushing the boundaries.
AB  - BACKGROUND AND PURPOSE: If magnetic resonance imaging (MRI) is to compete with
      computed tomography for evaluation of patients with acute ischemic stroke, there
      is a need for further improvements in acquisition speed. METHODS: Inclusion
      criteria for this prospective, single institutional study were symptoms of acute
      ischemic stroke within 24 hours onset, National Institutes of Health Stroke Scale
      >=3, and absence of MRI contraindications. A combination of echo-planar imaging
      (EPI) and a parallel acquisition technique were used on a 3T magnetic resonance
      (MR) scanner to accelerate the acquisition time. Image analysis was performed
      independently by 2 neuroradiologists. RESULTS: A total of 62 patients met
      inclusion criteria. A repeat MRI scan was performed in 22 patients resulting in a
      total of 84 MRIs available for analysis. Diagnostic image quality was achieved in
      100% of diffusion-weighted imaging, 100% EPI-fluid attenuation inversion recovery
      imaging, 98% EPI-gradient recalled echo, 90% neck MR angiography and 96% of brain
      MR angiography, and 94% of dynamic susceptibility contrast perfusion scans with
      interobserver agreements (k) ranging from 0.64 to 0.84. Fifty-nine patients (95%)
      had acute infarction. There was good interobserver agreement for EPI-fluid
      attenuation inversion recovery imaging findings (k=0.78; 95% confidence interval,
      0.66-0.87) and for detection of mismatch classification using dynamic
      susceptibility contrast-Tmax (k=0.92; 95% confidence interval, 0.87-0.94).
      Thirteen acute intracranial hemorrhages were detected on EPI-gradient recalled
      echo by both observers. A total of 68 and 72 segmental arterial stenoses were
      detected on contrast-enhanced MR angiography of the neck and brain with k=0.93,
      95% confidence interval, 0.84 to 0.96 and 0.87, 95% confidence interval, 0.80 to
      0.90, respectively. CONCLUSIONS: A 6-minute multimodal MR protocol with good
      diagnostic quality is feasible for the evaluation of patients with acute ischemic
      stroke and can result in significant reduction in scan time rivaling that of the
      multimodal computed tomographic protocol.

PMID- 24916907
TI  - Critique of Effective Anticoagulation with Factor Xa Next Generation in Atrial
      Fibrillation trial.

PMID- 24916909
TI  - Can response-adaptive randomization increase participation in acute stroke
      trials?
AB  - BACKGROUND AND PURPOSE: A response-adaptive randomization (RAR) trial design
      actively adjusts the ratio of participants assigned to each trial arm, favoring
      the better performing treatment by using outcome data from participants already
      in the trial. Compared with a standard clinical trial, an RAR study design has
      the potential to improve patient participation in acute stroke trials. METHODS:
      This cross-sectional randomized survey included adult emergency department
      patients, age>=18, without symptoms of stroke or other critical illness. A
      standardized protocol was used, and subjects were randomized to either an RAR or
      standard hypothetical acute stroke trial. After viewing the video describing the
      hypothetical trial (http://youtu.be/cKIWduCaPZc), reviewing the consent form, and
      having questions answered, subjects indicated whether they would consent to the
      trial. A multivariable logistic regression model was fitted to estimate the
      impact of RAR while controlling for demographic factors and patient understanding
      of the design. RESULTS: A total of 418 subjects (210 standard and 208 RAR) were
      enrolled. All baseline characteristics were balanced between groups. There was
      significantly higher participation in the RAR trial (67.3%) versus the standard
      trial (54.5%), absolute increase: 12.8% (95% confidence interval, 3.7-22.2). The
      RAR group had a higher odds ratio of agreeing to research (odds ratio, 1.89; 95%
      confidence interval, 1.2-2.9) while adjusting for patient level factors. Trial
      designs were generally well understood by the participants. CONCLUSIONS: The
      hypothetical RAR trial attracted more research participation than standard
      randomization. RAR has the potential to increase recruitment and offer benefit to
      future trial participants.

PMID- 24916908
TI  - Emergence of the primary pediatric stroke center: impact of the thrombolysis in
      pediatric stroke trial.
AB  - BACKGROUND AND PURPOSE: In adult stroke, the advent of thrombolytic therapy led
      to the development of primary stroke centers capable to diagnose and treat
      patients with acute stroke rapidly. We describe the development of primary
      pediatric stroke centers through preparation of participating centers in the
      Thrombolysis in Pediatric Stroke (TIPS) trial. METHODS: We collected data from
      the 17 enrolling TIPS centers regarding the process of becoming an acute
      pediatric stroke center with capability to diagnose, evaluate, and treat
      pediatric stroke rapidly, including use of thrombolytic therapy. RESULTS: Before
      2004, <25% of TIPS sites had continuous 24-hour availability of acute stroke
      teams, MRI capability, or stroke order sets, despite significant pediatric stroke
      expertise. After TIPS preparation, >80% of sites now have these systems in place,
      and all sites reported increased readiness to treat a child with acute stroke.
      Use of a 1- to 10-Likert scale on which 10 represented complete readiness, median
      center readiness increased from 6.2 before site preparation to 8.7 at the time of
      site activation (P<=0.001). CONCLUSIONS: Before preparing for TIPS, centers
      interested in pediatric stroke had not developed systematic strategies to
      diagnose and treat acute pediatric stroke. TIPS trial preparation has resulted in
      establishment of pediatric acute stroke centers with clinical and system
      preparedness for evaluation and care of children with acute stroke, including use
      of a standardized protocol for evaluation and treatment of acute arterial stroke
      in children that includes use of intravenous tissue-type plasminogen activator.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01591096.

PMID- 24916910
TI  - Response to letter regarding article, "Targeting recombinant tissue-type
      plasminogen activator in acute ischemic stroke based on risk of intracranial
      hemorrhage or poor functional outcome: an analysis of the Third International
      Stroke Trial".

PMID- 24916911
TI  - Modification of outcomes with aspirin or apixaban in relation to female and male
      sex in patients with atrial fibrillation: a secondary analysis of the AVERROES
      study.
AB  - BACKGROUND AND PURPOSE: The main objective of the present analysis was to assess
      the effect of treatment with aspirin compared with apixaban on ischemic stroke
      and major bleeding in women compared with men. Female patients with atrial
      fibrillation are at increased stroke risk compared with male patients, and the
      underlying reasons for higher risk are uncertain. METHODS: Ancillary analysis of
      the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial
      Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist
      Treatment (AVERROES) trial, comparing aspirin and apixaban, focused on sex
      differences. Mean follow-up was 1.1 years. RESULTS: Women compared with men
      tended to be older (aspirin, 71.8 versus 68.8 years; apixaban, 71.4 versus 68.6
      years), with a higher proportion of those aged>=75 years. Also, women had less
      peripheral artery disease (aspirin, 2.4% versus 3.7%; apixaban, 1.4% versus
      3.0%), more heart failure, and higher mean CHADS2 (congestive heart failure,
      hypertension, age of 75 years or older, diabetes [1 point each], stroke or
      transient ischemic attack [2 points]) scores (aspirin, 2.2 versus 2.0; apixaban,
      2.1 versus 2.0). Women compared with men had higher ischemic stroke rates
      (aspirin, 3.99% versus 2.28%; apixaban, 1.55% versus 0.82%) but similar bleeding
      rates (aspirin, 1.29% versus 1.22%; apixaban, 1.15% versus 1.36%). The relative
      effect of apixaban compared with aspirin was similar in men and women for both
      ischemic stroke (women, 3.99% versus 1.55%; hazard ratio, 0.39; 95% confidence
      interval, 0.23-0.64; men, 2.28% versus 0.82%; hazard ratio, 0.36; 95% confidence
      interval, 0.19-0.63; Pint=0.84) and major bleeding (women, 1.29% versus 1.15%;
      hazard ratio, 1.15; 95% confidence interval, 0.59-2.23; men, 1.36% versus 1.22%;
      hazard ratio, 1.13; 95% confidence interval, 0.64-2.02; Pint=0.96). CONCLUSIONS:
      Female patients with atrial fibrillation had higher ischemic stroke rates
      compared with male patients, but the relative effects of apixaban compared with
      aspirin on both ischemic stroke and bleeding were similar in men and women.

PMID- 24916912
TI  - Length of occlusion predicts recanalization and outcome after intravenous
      thrombolysis in middle cerebral artery stroke.
AB  - BACKGROUND AND PURPOSE: The length of large vessel occlusion is considered a
      major factor for therapy in patients with ischemic stroke. We used 4D-CT
      angiography evaluation of middle cerebral artery occlusion in prediction of
      recanalization and favorable clinical outcome and after intravenous thrombolysis
      (IV-tPA). METHODS: In 80 patients treated with IV-tPA for acute complete middle
      cerebral artery/M1 occlusion determined using CT angiography and temporal maximum
      intensity projection, calculated from 4D-CT angiography, the length of middle
      cerebral artery proximal stump, occlusion in M1 or M1 and M2 segment were
      measured. Univariate and multivariate analyses were performed to define
      independent predictors of successful recanalization after 24 hours and favorable
      outcome after 3 months. RESULTS: The length of occlusion was measureable in all
      patients using temporal maximum intensity projection. Recanalization thrombolysis
      in myocardial infarction 2 to 3 was achieved in 37 individuals (46%). The
      extension to M2 segment as a category (odds ratio, 4.58; 95% confidence interval,
      1.39-15.05; P=0.012) and the length of M1 segment occlusion (odds ratio, 0.82;
      95% confidence interval, 0.73-0.92; P=0.0007) with an optimal cutoff value of 12
      mm (sensitivity 0.67; specificity 0.71) were significant independent predictors
      of recanalization. Favorable outcome (modified Rankin scale 0-2) was achieved in
      25 patients (31%), baseline National Institutes of Health Stroke Scale (odds
      ratio, 0.82; 95% confidence interval, 0.72-0.93; P=0.003) and the length of
      occlusion M1 in segment (odds ratio, 0.79; 95% confidence interval, 0.69-0.91;
      P=0.0008) with an optimal cutoff value of 11 mm (sensitivity 0.74; specificity
      0.76) were significant independent predictors of favorable outcome. CONCLUSIONS:
      The length of middle cerebral artery occlusion is an independent predictor of
      successful IV-tPA treatment.

PMID- 24916913
TI  - Leukocyte invasion of the brain after experimental intracerebral hemorrhage in
      mice.
AB  - BACKGROUND AND PURPOSE: Neuroinflammatory processes contribute to secondary
      neuronal damage after intracerebral hemorrhage. We aimed to characterize the time
      course of brain immigration of different leukocyte subsets after striatal
      injection of either autologous blood or collagenase in mice. METHODS:
      Intracerebral hemorrhage was induced by injection of either autologous blood (20
      MUL) or collagenase (0.03 U) in C57Bl/6J mice. Hematoma volumetry was performed
      on cryosections. Blood volume was measured by hemoglobin spectrophotometry.
      Leukocytes were isolated from hemorrhagic hemisphere 1, 3, 5, and 14 days after
      intracerebral hemorrhage, stained for leukocyte markers, and measured by flow
      cytometry. Heterologous blood injection from CD45.1 mice was used to investigate
      the origin of brain-invading leukocytes. RESULTS: Collagenase injection induced a
      larger hematoma volume but a similar blood content compared with blood injection.
      Cerebral leukocyte infiltration in the hemorrhagic hemisphere was similar in both
      models. The majority of leukocytes isolated from the brain originated from the
      circulation. CD4+ T lymphocytes were the predominant brain leukocyte population
      in both models. However, cerebral granulocyte counts were higher after
      collagenase compared with blood injection. CONCLUSIONS: Brain infiltration of
      systemic immune cells is similar in both murine intracerebral hemorrhage models.
      The pathophysiological impact of invading leukocytes and, in particular, of T
      cells requires further investigation.

PMID- 24916914
TI  - Picometre-precision analysis of scanning transmission electron microscopy images
      of platinum nanocatalysts.
AB  - Measuring picometre-scale shifts in the positions of individual atoms in
      materials provides new insight into the structure of surfaces, defects and
      interfaces that influence a broad variety of materials' behaviour. Here we
      demonstrate sub-picometre precision measurements of atom positions in aberration
      corrected Z-contrast scanning transmission electron microscopy images based on
      the non-rigid registration and averaging of an image series. Non-rigid
      registration achieves five to seven times better precision than previous methods.
      Non-rigidly registered images of a silica-supported platinum nanocatalyst show pm
      scale contraction of atoms at a (111)/(111) corner towards the particle centre
      and expansion of a flat (111) facet. Sub-picometre precision and standardless
      atom counting with <1 atom uncertainty in the same scanning transmission electron
      microscopy image provide new insight into the three-dimensional atomic structure
      of catalyst nanoparticle surfaces, which contain the active sites controlling
      catalytic reactions.

PMID- 24916915
TI  - Identification of GPM6A and GPM6B as potential new human lymphoid leukemia
      associated oncogenes.
AB  - BACKGROUND: Previously, we found that the Graffi murine leukemia virus (MuLV) is
      able to induce a wide spectrum of hematologic malignancies in vivo. Using high
      density oligonucleotide microarrays, we established the gene expression profiles
      of several of these malignancies, thereby specifically focusing on genes
      deregulated in the lymphoid sub-types. We observed over-expression of a variety
      of genes, including Arntl2, Bfsp2, Gfra2, Gpm6a, Gpm6b, Nln, Fbln1, Bmp7, Etv5
      and Celsr1 and, in addition, provided evidence that Fmn2 and Parm-1 may act as
      novel oncogenes. In the present study, we assessed the expression patterns of
      eight selected human homologs of these genes in primary human B-cell
      malignancies, and explored the putative oncogenic potential of GPM6A and GPM6B.
      METHODS: The gene expression levels of the selected human homologs were tested in
      human B-cell malignancies by semi-quantitative RT-PCR. The protein expression
      profiles of human GPM6A and GPM6B were analyzed by Western blotting. The
      localization and the effect of GPM6A and GPM6B on the cytoskeleton were
      determined using confocal and indirect immunofluorescence microscopy. To confirm
      the oncogenic potential of GPM6A and GPM6B, classical colony formation assays in
      soft agar and focus forming assays were used. The effects of these proteins on
      the cell cycle were assessed by flow cytometry analysis. RESULTS: Using semi
      quantitative RT-PCR, we found that most of the primary B-cell malignancies
      assessed showed altered expression patterns of the genes tested, including GPM6A
      and GPM6B. Using confocal microscopy, we found that the GPM6A protein (isoform 3)
      exhibits a punctate cytoplasmic localization and that the GPM6B protein (isoform
      4) exhibits a peri-nuclear and punctate cytoplasmic localization. Interestingly,
      we found that exogenous over-expression of both proteins in NIH/3T3 cells alters
      the actin and microtubule networks and induces the formation of long filopodia
      like protrusions. Additionally, we found that these over-expressing NIH/3T3 cells
      exhibit anchorage-independent growth and enhanced proliferation rates. Cellular
      transformation (i.e., loss of contact inhibition) was, however, only observed
      after exogenous over-expression of GPM6B. CONCLUSIONS: Our results indicate that
      several human homologs of the genes found to be deregulated in Graffi MuLV
      experimental mouse models may serve as candidate biomarkers for human B-cell
      malignancies. In addition, we found that GPM6A and GPM6B may act as novel
      oncogenes in the development of these malignancies.

PMID- 24916917
TI  - Preliminary study of the Southampton Hand Assessment Procedure for Children and
      its reliability.
AB  - BACKGROUND: The Southampton Hand Assessment Procedure (SHAP) is currently used in
      the adult population for evaluating the functionality of impaired or prosthetic
      hands. The SHAP cannot be used for children because of the relatively larger size
      of the objects used to perform SHAP tasks and unknown clinimetric properties. The
      aims of this study were to adapt the SHAP for use in children (SHAP-C), to
      determine norm values for the SHAP-C, and to analyze the reliability of the SHAP
      C. METHODS: The SHAP-C was adapted based on the SHAP protocol. Some objects were
      downsized, and the timing of tasks was performed by the rater instead of the
      participant. Intra- and inter-rater reliability were assessed in 24 children (5
      [0.54] y/o) with unimpaired hands. The repeatability coefficients (RCs) were
      calculated. An RC <= 75% of the mean SHAP-C task values was considered good
      reliability. RESULTS: Participants were able to perform all SHAP-C tasks. The
      means of the SHAP-C tasks ranged from 0.75 to 1.21 seconds for abstract objects
      and from 0.64-19.13 seconds for activities of daily living. The RCs of a single
      assessor did not exceed 75% in 17/26 SHAP-C tasks, displaying a relatively good
      intra-rater reliability, whereas the RCs for the inter-rater reliability exceeded
      75% in 22/26 SHAP-C tasks, thus displaying poor reliability. CONCLUSION: In this
      first study that adjusted the SHAP for pediatric use, we found that all SHAP-C
      objects and tasks could be performed by children. The intra-rater reliability was
      better than the inter-rater reliability. Although the SHAP-C appears to be a
      promising instrument, the protocol requires further modifications to provide
      reliable measurements in children.

PMID- 24916916
TI  - Testing demographic differences for alcohol use initiation among adolescents for
      the decisional balance and situational temptation prevention inventories.
AB  - Alcohol use by middle school-aged students is a public health concern because of
      the numerous adverse social, health and psychological outcomes. Prevention
      programs attempt to intervene before alcohol use begins. A tailored, computer
      delivered program for the prevention of alcohol use and a series of new
      transtheoretical model measures were developed, including decisional balance
      (Pros and Cons) of alcohol use and Situational Temptations to Try Alcohol. This
      study investigated if there were any demographic differences on these measures in
      a sample of 6th grade middle school students from 20 schools (N=4151) at
      baseline. Three factorial analysis of variance tests were conducted to explore
      the impact of race (whites vs. non-whites), ethnicity (Hispanics vs. Non
      Hispanics) and gender (males vs. females). A significant two-way interaction
      effect was found between gender and ethnicity for Pros of Alcohol Use. A
      significant three-way interaction effect was found between gender, race and
      ethnicity for Cons of Alcohol Use. Main effects were found for the three
      demographic factors for Situational Temptations to Try Alcohol. However, the
      effect sizes for the interaction effects and main effects were very small (all
      below eta(2)=.01), suggesting that race/ethnicity and gender alone may not be
      highly influential factors in the Decisional Balance for the Prevention of
      Alcohol and Situational Temptations to Try Alcohol in adolescence. The
      implications for these results and alcohol use prevention among this group are
      discussed. 

PMID- 24916918
TI  - Deregulation of miR-200b, miR-200c and miR-429 indicates its potential relevant
      role in patients with colorectal cancer liver metastasis.

PMID- 24916919
TI  - Neuroimaging and cognition using functional near infrared spectroscopy (fNIRS) in
      multiple sclerosis.
AB  - The present study utilized functional near infrared spectroscopy (fNIRS) to
      detect neural activation differences in the orbitofrontal brain region between
      individuals with multiple sclerosis (MS) and healthy controls (HCs) during a
      working memory (WM) task. Thirteen individuals with MS and 12 HCs underwent fNIRS
      recording while performing the n-back WM task with four levels of difficulty (0-,
      1-, 2-, and 3-back). Subjects were fitted with the fNIRS cap consisting of 30
      'optodes' positioned over the forehead. The results revealed different patterns
      of brain activation in MS and HCs. The MS group showed an increase in brain
      activation, as measured by the concentration of oxygenated hemoglobin (oxyHb), in
      the left superior frontal gyrus (LSFG) at lower task difficulty levels (i.e. 1
      back), followed by a decrease at higher task difficulty (2- and 3-back) as
      compared with the HC group. HC group achieved higher accuracy than the MS group
      on the lower task loads (i.e. 0- and 1-back), however there were no performance
      differences between the groups at the higher task loads (i.e. 2- and 3-back).
      Taken together, the results suggest that individuals with MS experience a task
      with the lower cognitive load as more difficult than the HC group, and the brain
      activation patterns observed during the task confirm some of the previous
      findings from functional magnetic resonance imaging (fMRI) studies. This study is
      the first to investigate brain activation by utilizing the method of fNIRS in MS
      during the performance of a cognitive task. 

PMID- 24916920
TI  - Memory detection with the Concealed Information Test: a meta analysis of skin
      conductance, respiration, heart rate, and P300 data.
AB  - The Concealed Information Test (CIT) uses psychophysiological measures to
      determine the presence or absence of crime-related information in a suspect's
      memory. We conducted a meta-analysis on the validity of the CIT based on four
      physiological measures-skin conductance response (SCR), respiration line length
      (RLL), changes in heart rate (HR), and enhanced amplitudes of the P300 component
      of the event-related potential (P300). This meta-analysis relied on laboratory
      studies that used either the mock-crime or the personal-item paradigm. Results
      showed a mean effect size (d*) of 1.55 for SCR, 1.11 for RLL, 0.89 for HR, and
      1.89 for P300. However, P300 outperformed SCR only in the personal-item paradigm,
      but not in the mock-crime paradigm. Motivation level, number of questions,
      publication year, and the inclusion of innocent participants emerged as
      significant moderators for the SCR, while only the type of paradigm used
      moderated the P300 effect.

PMID- 24916921
TI  - Studies on the factors modulating indole-3-acetic acid production in endophytic
      bacterial isolates from Piper nigrum and molecular analysis of ipdc gene.
AB  - AIMS: The study mainly aimed quantitative analysis of IAA produced by endophytic
      bacteria under various conditions including the presence of extract from Piper
      nigrum. Analysis of genetic basis of IAA production was also conducted by
      studying the presence and diversity of the ipdc gene among the selected isolates.
      MATERIALS AND METHODS: Five endophytic bacteria isolated previously from P.
      nigrum were used for the study. The effect of temperature, pH, agitation,
      tryptophan concentration and plant extract on modulating IAA production of
      selected isolates was analysed by colorimetric method. Comparative and
      quantitative analysis of IAA production by colorimetric isolates under optimal
      culture condition was analysed by HPTLC method. Presence of ipdc gene and thereby
      biosynthetic basis of IAA production among the selected isolates were studied by
      PCR-based amplification and subsequent insilico analysis of sequence obtained.
      CONCLUSIONS: Among the selected bacterial isolates from P. nigrum, isolate PnB 8
      (Klebsiella pneumoniae) was found to have the maximum yield of IAA under various
      conditions optimized and was confirmed by colorimetric, HPLC and HPTLC analysis.
      Very interestingly, the study showed stimulating effect of phytochemicals from P.
      nigrum on IAA production by endophytic bacteria isolated from same plant.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study is unique because of the
      selection of endophytes from same source for comparative and quantitative
      analysis of IAA production under various conditions. Study on stimulatory effect
      of phytochemicals on bacterial IAA production as explained in the study is a
      novel approach. Studies on molecular basis of IAA production which was confirmed
      by sequence analysis of ipdc gene make the study scientifically attractive. Even
      though microbial production of IAA is well known, current report on detailed
      optimization, effect of plant extract and molecular confirmation of IAA
      biosynthesis is comparatively novel in its approach.

PMID- 24916923
TI  - Factors Influencing Facebook Usage and Facebook Addictive Tendency in University
      Students: The Role of Online Psychological Privacy and Facebook Usage Motivation.
AB  - There are few studies analysing the influence of personal traits and motivation
      factors on Facebook usage and Facebook addictive tendency as seen in university
      students. In this study, 225 Taiwanese university students completed a
      questionnaire to determine their online psychological privacy scale, Facebook
      usage motivation scale, Facebook usage scale and Facebook addictive tendency
      scale, in order to evaluate the items that can be conceptualized as the effect of
      university students' online psychological privacy personal trait and motive
      factors, and Facebook usage motivation with respect to Facebook usage and
      Facebook addictive tendency. The study found that a desire for more online
      psychological privacy correlates with a stronger motivation to use Facebook and
      more Facebook usage behaviour among university students who may become high-risk
      groups for Facebook addictive tendency. The study found that a desire for or an
      acceptance of a lower online psychological privacy correlates with a stronger
      motivation to use Facebook among university students who may have more Facebook
      usage behaviour. This study can help understand university students' Facebook
      usage and Facebook addictive tendency and provide feature indicators for those
      who may become high-risk groups for Facebook addictive tendency. Finally, this
      study conducts discussion and proposes relevant suggestions for future study.

PMID- 24916922
TI  - Hypertonic saline alleviates cerebral edema by inhibiting microglia-derived TNF
      alpha and IL-1beta-induced Na-K-Cl Cotransporter up-regulation.
AB  - BACKGROUND: Hypertonic saline (HS) has been successfully used clinically for
      treatment of various forms of cerebral edema. Up-regulated expression of Na-K-Cl
      Cotransporter 1 (NKCC1) and inflammatory mediators such as tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) has been demonstrated to be
      closely associated with the pathogenesis of cerebral edema resulting from a
      variety of brain injuries. This study aimed to explore if alleviation of cerebral
      edema by 10% HS might be effected through down-regulation of inflammatory
      mediator expression in the microglia, and thus result in decreased NKCC1
      expression in astrocytes in the cerebral cortex bordering the ischemic core.
      METHODS: The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral
      artery occlusion (MCAO) were used for assessment of NKCC1, TNF-alpha and IL-1beta
      expression using Western blotting, double immunofluorescence and real time RT
      PCR, and the model also was used for evaluation of brain water content (BWC) and
      infarct size. SB203580 and SP600125, specific inhibitors of the p38 and JNK
      signaling pathways, were used to treat primary microglia cultures to determine
      whether the two signaling pathways were required for the inhibition of HS on
      microglia expressing and secreting TNF-alpha and IL-1beta using Western blotting,
      double immunofluorescence and enzyme-linked immunosorbent assay (ELISA). The
      effect of TNF-alpha and IL-1beta on NKCC1 expression in primary astrocyte
      cultures was determined. In addition, the direct inhibitory effect of HS on NKCC1
      expression in primary astrocytes was also investigated by Western blotting,
      double immunofluorescence and real time RT-PCR. RESULTS: BWC and infarct size
      decreased significantly after 10% HS treatment. TNF-alpha and IL-1beta
      immunoexpression in microglia was noticeably decreased. Concomitantly, NKCC1
      expression in astrocytes was down-regulated. TNF-alpha and IL-1beta released from
      the primary microglia subjected to hypoxic exposure and treatment with 100 mM HS
      were decreased. NKCC1 expression in primary astrocytes was concurrently and
      progressively down-regulated with decreasing concentration of exogenous TNF-alpha
      and IL-1beta. Additionally, 100 mM HS directly inhibited NKCC1 up-regulation in
      astrocytes under hypoxic condition. CONCLUSIONS: The results suggest that 10% HS
      alleviates cerebral edema through inhibition of the NKCC1 Cotransporter, which is
      mediated by attenuation of TNF-alpha and IL-1beta stimulation on NKCC1.

PMID- 24916924
TI  - A biocompatible alkene hydrogenation merges organic synthesis with microbial
      metabolism.
AB  - Organic chemists and metabolic engineers use orthogonal technologies to construct
      essential small molecules such as pharmaceuticals and commodity chemicals. While
      chemists have leveraged the unique capabilities of biological catalysts for small
      molecule production, metabolic engineers have not likewise integrated reactions
      from organic synthesis with the metabolism of living organisms. Reported herein
      is a method for alkene hydrogenation which utilizes a palladium catalyst and
      hydrogen gas generated directly by a living microorganism. This biocompatible
      transformation, which requires both catalyst and microbe, and can be used on a
      preparative scale, represents a new strategy for chemical synthesis that combines
      organic chemistry and metabolic engineering. 

PMID- 24916925
TI  - Actual endoscopic versus predicted surgical mortality for treatment of advanced
      mucosal neoplasia of the colon.
AB  - BACKGROUND: EMR of advanced mucosal neoplasia (AMN) (ie, sessile or laterally
      spreading lesions of >=20 mm) of the colon has become an increasingly popular
      alternative to surgical resection. However, data regarding safety and mortality
      of EMR in comparison to surgery are limited. OBJECTIVE: To compare actual
      endoscopic with predicted surgical mortality. DESIGN: Prospective, observational,
      multicenter cohort study. SETTING: Academic, high-volume, tertiary-care referral
      center. PATIENTS: Consecutive patients referred for EMR. INTERVENTION EMR MAIN
      OUTCOME MEASUREMENTS: To predict hypothetical surgical mortality, the Association
      of Coloproctology of Great Britain and Ireland score, composed of physiological
      and surgical components, was calculated for each patient. Predicted surgical
      mortality was then compared with actual outcomes of EMR. The results were
      validated by an unselected subcohort by using the Colorectal Physiologic and
      Operative Severity Score for Enumeration of Mortality and Morbidity. RESULTS:
      Among 1050 patients with AMN treated by EMR, including patients with a predicted
      mortality rate of greater than 5% (13.8% of cohort), no deaths occurred within 30
      days after the procedure. The predicted surgical mortality rate was 3.3% with the
      Association of Coloproctology of Great Britain and Ireland score (P < .0001).
      This suggests a significant advantage of EMR over surgery. The results were
      validated by using the Colorectal Physiologic and Operative Severity Score for
      Enumeration of Mortality and Morbidity in 390 patients predicting a surgical
      mortality rate of 3.2% (P = .0003). LIMITATIONS: Nonrandomized study. CONCLUSION:
      In this large multicenter study of EMR for colonic AMN, the predicted surgical
      mortality rate was significantly higher than the actual endoscopic mortality
      rate. Given that endoscopic therapy is less morbid and less expensive than
      surgery and can be performed as an outpatient treatment, it should be considered
      as the first line of treatment for most patients with these lesions.

PMID- 24916926
TI  - Submucosal tunneling endoscopic resection of a giant esophageal leiomyoma.

PMID- 24916927
TI  - Shape covariation between the craniofacial complex and first molars in humans.
AB  - The occurrence of mutual genetic loci in morphogenesis of the face and teeth
      implies shape covariation between these structures. However, teeth finalize their
      shape at an early age, whereas the face grows and is subjected to environmental
      influences for a prolonged period; it is therefore conceivable that covariation
      might modulate with age. Here we investigate the extent of this covariation in
      humans by measuring the 3D shape of the occlusal surface of the permanent first
      molars and the shape of the craniofacial complex from lateral radiographs, at two
      maturations stages. A sample of Greek subjects was divided into two groups (110
      adult, 110 prepubertal) with equally distributed gender. The occlusal surfaces of
      the right first molars were 3D scanned from dental casts; 265 and 274 landmarks
      (including surface and curve semilandmarks) were digitized on the maxillary and
      mandibular molars, respectively. The corresponding lateral cephalometric
      radiographs were digitized with 71 landmarks. Geometric morphometric methods were
      used to assess shape variation and covariation. The vertical dimension of the
      craniofacial complex was the main parameter of shape variation, followed by
      anteroposterior deviations. The male craniofacial complex was larger (4.0-5.7%)
      and was characterized by a prominent chin and clockwise rotation of the cranial
      base (adult group only). Allometry was weak and statistically significant only
      when examined for the sample as a whole (percent variance explained: 2.1%, P =
      0.0002). Covariation was statistically significant only between the lower first
      molar and the craniofacial complex (RV = 14.05%, P = 0.0099, and RV = 12.31%, P =
      0.0162, for the prepubertal and adult groups, respectively). Subtle age-related
      covariation differences were noted, indicating that environmental factors may
      influence the pattern and strength of covariation. However, the main pattern was
      similar in both groups: a class III skeletal pattern (relative maxillary
      retrusion and mandibular protrusion), hyperdivergency, forward rotation of the
      posterior cranial base and upward rotation of the anterior cranial base were
      associated with mesiodistal elongation of the lower molars and height reduction
      of their distal cusps. This pattern mimics phylogeny in humans, where flexion and
      counterclockwise rotation of the cranial base, considered advantageous to
      survival, co-occur with tooth reductions that cannot be easily explained in
      evolutionary terms. The similarity of the phylogenetic and covariation patterns
      seems to support the pleiotropic gene hypothesis. 

PMID- 24916928
TI  - Using logistic regression to improve the prognostic value of microarray gene
      expression data sets: application to early-stage squamous cell carcinoma of the
      lung and triple negative breast carcinoma.
AB  - BACKGROUND: Numerous microarray-based prognostic gene expression signatures of
      primary neoplasms have been published but often with little concurrence between
      studies, thus limiting their clinical utility. We describe a methodology using
      logistic regression, which circumvents limitations of conventional Kaplan Meier
      analysis. We applied this approach to a thrice-analyzed and published squamous
      cell carcinoma (SQCC) of the lung data set, with the objective of identifying
      gene expressions predictive of early death versus long survival in early-stage
      disease. A similar analysis was applied to a data set of triple negative breast
      carcinoma cases, which present similar clinical challenges. METHODS: Important to
      our approach is the selection of homogenous patient groups for comparison. In the
      lung study, we selected two groups (including only stages I and II), equal in
      size, of earliest deaths and longest survivors. Genes varying at least four-fold
      were tested by logistic regression for accuracy of prediction (area under a ROC
      plot). The gene list was refined by applying two sliding-window analyses and by
      validations using a leave-one-out approach and model building with validation
      subsets. In the breast study, a similar logistic regression analysis was used
      after selecting appropriate cases for comparison. RESULTS: A total of 8594
      variable genes were tested for accuracy in predicting earliest deaths versus
      longest survivors in SQCC. After applying the two sliding window and the leave
      one-out analyses, 24 prognostic genes were identified; most of them were B-cell
      related. When the same data set of stage I and II cases was analyzed using a
      conventional Kaplan Meier (KM) approach, we identified fewer immune-related genes
      among the most statistically significant hits; when stage III cases were
      included, most of the prognostic genes were missed. Interestingly, logistic
      regression analysis of the breast cancer data set identified many immune-related
      genes predictive of clinical outcome. CONCLUSIONS: Stratification of cases based
      on clinical data, careful selection of two groups for comparison, and the
      application of logistic regression analysis substantially improved predictive
      accuracy in comparison to conventional KM approaches. B cell-related genes
      dominated the list of prognostic genes in early stage SQCC of the lung and triple
      negative breast cancer.

PMID- 24916929
TI  - Total IgE and eotaxin (CCL11) contents in tears of patients suffering from
      seasonal allergic conjunctivitis.
AB  - BACKGROUND: To prospectively investigate patients with seasonal allergic
      conjunctivitis (SAC) during the pollen season and test associations between tears
      total IgE, eotaxin concentrations, and SAC severity. METHODS: Enrolled patients
      presented ocular symptoms and clinical signs of SAC at the time of presentation.
      Ocular itching, hyperaemia, chemosis, eyelid swelling, and tearing were scored,
      and the sum of these scores was defined as the clinical score. Conjunctival
      papillae were separately graded. We measured eotaxin concentration in tears by an
      enzyme-linked immunosorbent assay (ELISA) and total tear IgE by Lacrytest strip.
      RESULTS: Among thirty patients (30 eyes), 11 showed neither tear IgE nor tear
      eotaxin, while 15 out of 19 patients with positive IgE values presented a
      positive amount of eotaxin in their tears (Fisher's test: p < 0.001). The mean
      eotaxin concentration was 641 +/- 154 (SEM) pg/ml. In patients with no amount of
      tear IgE, we observed a lower conjunctival papilla grade than in patients whose
      tears contained some amount of IgE (trend test: p = 0.032). In the 15 patients
      whose tear eotaxin concentration was null, tear IgE concentration was 5.3 +/- 3.5
      arbitrary units; in the other 15 patients whose eotaxin was positive, IgE reached
      21 +/- 4.3 arbitrary U (Mann-Whitney: p < 0.001). We measured 127 +/- 47 pg/ml
      eotaxin in patients with no history of SAC but newly diagnosed as suffering from
      SAC, and 852 +/- 218 pg/ml eotaxin in patients with a known SAC (p = 0.008). In
      contrast, tear IgE concentrations of both groups did not differ statistically
      significantly (p = 0.947). CONCLUSIONS: If IgE and eotaxin secreted in tears are
      major contributors in SAC pathogenesis, they however act at different steps of
      the process.

PMID- 24916931
TI  - Editorial.

PMID- 24916932
TI  - How to improve adherence to antipsychotic treatment: Outcomes of the IMproving
      PAtient outComes in psychiaTry (IMPACT) Berlin 2009 meeting workshop.
AB  - Objective. To challenge psychiatrists about their practice regarding patients'
      treatment adherence in severe mental disease, and make them discuss possible ways
      to improve this through their relationship with patients. Methods. A total of 423
      physicians from 32 countries were assigned across 41 parallel groups during a
      workshop organised on adherence in severe mental diseases. Factors that influence
      adherence, and questions and measures to help patient-clinician interaction were
      discussed and rated. Results. The most important factor influencing adherence to
      treatment was considered to be insight. The factor over which clinicians felt
      they had the greatest influence was the therapeutic relationship. The question
      that most physicians considered the most useful for improving communication with
      patients was, "Does taking medication cause any problems for you?" Additional
      areas identified as important in improving adherence included addressing the
      positive and negative aspects of medication, patient expectations and what
      patients hoped to gain from seeing their physician. Intervention programmes to
      improve adherence included patient education, motivational interviewing and
      cognitive-behavioural therapy. A composite toolkit based on the top-rated
      questions to improve communication with patients and measures to aid adherence
      was recommended. Conclusion. Patient-centred practice is fundamental to ensuring
      adherence in mentally ill patients. Working tools can be successfully developed
      in interactive workshop settings, through reviewing and challenging current
      clinical practice. 

PMID- 24916930
TI  - CD44 and RHAMM hyaluronan receptors in human ocular surface inflammation.
AB  - BACKGROUND: CD44 and RHAMM hyaluronan (HA) receptors have been studied in several
      systemic diseases such as osteoarthritis and cancer. However, not too much is
      known about their role in ocular surface disorders. The purpose of this research
      was to determine if CD44 and RHAMM are implicated in human ocular surface
      inflammation. METHODS: Upper tarsal conjunctival epithelial samples from patients
      with active ocular surface inflammation (n = 17) and healthy controls (n = 14)
      were recovered by brush cytology. Patients were evaluated by an ophthalmologist
      and classified in different groups according to the etiology (immune atopic
      diseases or immune non-atopic diseases) and inflammation intensity (mild/moderate
      or severe). CD44, RHAMM, and p53 mRNAs were measured using real-time PCR.
      RESULTS: CD44, RHAMM, and p53 mRNAs were detected in all samples. In immune
      atopic diseases, higher levels of CD44 and RHAMM mRNAs were present, reaching a
      300 % increase for RHAMM in severe inflammation (p < 0.001). In contrast, in
      immune non-atopic diseases, the HA receptors were downregulated. CD44 tended to
      decrease up to 30 % in severe patients (p = 0.06), and RHAMM decreased 40 % in
      severe inflammation (p = 0.021). CONCLUSIONS: RHAMM may be implicated in severe
      ocular surface inflammation affecting the upper tarsal conjunctiva.

PMID- 24916933
TI  - The use of prn medication in a child and adolescent mental health inpatient
      service in France.
AB  - Objective. The aim of this study was to investigate the use of "as needed" (pro
      re nata or prn) psychotropic medication in a child and adolescent psychiatric
      inpatient population. The study was carried out on the psychiatry ward of a
      paediatric teaching hospital in Paris, France. Methods. A prospective analysis of
      prn psychotropic drug prescriptions and administrations was conducted for all
      patients hospitalised over a period of 4 months. The study group consisted of 187
      patients. Results. In total, 93 prn prescriptions were written, for 27% of the
      patients (51) but only 14% (26) received a total of 76 administrations.
      Antipsychotic drugs accounted for 54% of the prescriptions, anxiolytics for 33%,
      antiepileptic drugs for 8%, antiparkinsonian drugs for 4% and hypnotic drugs for
      1%. Anxiety was the reason given for 67% of the prn administrations, with
      hydroxyzine used in 69% of these cases. Disruptive behaviour accounted for 22% of
      prn administrations, with antipsychotic drugs accounting for 88% of these
      administrations. Insomnia accounted for 8% of prn administrations, and
      antipsychotic drug-induced dystonia accounted for 3% of such administrations.
      Conclusion. Controlled studies are required to assess the efficacy and safety of
      prn medication and the conditions in which its use is indicated. 

PMID- 24916934
TI  - The relationship between elderly suicides rates, household size and family
      structure: A cross-national study.
AB  - Background. Cultural factors may influence cross-national variations in elderly
      suicide rates. Methods. A cross-national study examining the relationship between
      elderly suicide rates and (i) mean household size and (ii) family structure was
      conducted with the "a priori" unidirectional hypothesis that larger mean
      household size and greater proportion of extended families may imply a greater
      number of people being potentially available within the household to provide
      support and respect to the elderly and to hold them in high esteem, and
      ultimately leading to reduction in elderly suicide rates. Data on elderly suicide
      rates was ascertained from the World Health Organisation website. Data on mean
      household size and family structure was ascertained from a report from the Inter
      American Development Bank. Results. The main findings were elderly suicide rates
      in both sexes were significantly correlated with the mean household size
      (negative), percentage of extended households (negative; except in males aged 65
      74 years where this approached significance) and percentage of single person
      households (positive). Conclusions. The impact of mean household size and family
      structure on elderly suicide rates may interact with and be modified and mediated
      through cultural factors. The contribution of cross-national differences in
      cultural factors on elderly suicide rates requires further study by formally
      measuring cultural factors with validated instruments. 

PMID- 24916935
TI  - Mood regulation beliefs in depressed psychiatric inpatients: Examining affect,
      behavior, cognitive, and social strategies.
AB  - The present study was designed to evaluate patient expectations regarding their
      ability to manage negative emotional reactions. Strategies for managing negative
      emotional reactions were classified in terms of a focus on affect regulation,
      behavioral activation, cognitive restructuring, and social involvement. Depressed
      psychiatric inpatients (N=137) reported weak expectations regarding their ability
      to regulate their negative moods (M = 82.37, SD = 16.61). Depression severity was
      closely related to male patients' expectations regarding their ability to control
      negative moods through affect regulation (r(44)=- 0.37, P<0.05), behavioral
      activation (r(44)=- 0.59, P< 0.01), cognitive restructuring (r(44)- 0.50,
      P<0.01), and social involvement (r(44)=- 0.33, P<0.05). Suicide risk was
      significantly related to male patients' expectations regarding their ability to
      control negative moods. Similar results were observed for female patients. Recent
      suicide attempters, past attempters, and non-suicidal depressed inpatients
      reported similar mood regulation expectations (F(2,134)=0.46, ns). Therapy may
      help patients develop confidence in their ability to manage negative emotional
      reactions. It may be useful to assess patient expectations in order to guide
      therapy toward specific coping actions that may help them control their negative
      moods. 

PMID- 24916936
TI  - Does adversity earlier in life affect elderly suicide rates? A cross-national
      study.
AB  - Background. Although life-long adversity has been suggested as a protective
      factor for elderly suicides, studies examining protective factors for elderly
      suicides are scarce. Methods. The relationship between elderly suicide rates and
      five proxy measures of adversity earlier in life was examined using data from the
      World Health Organisation and the United Nations data banks. Results. Suicide
      rates on univariate analysis, in males and females in both the elderly age-bands,
      were lower when the severity of adversity was higher for at least four of the
      five proxy measures of adversity earlier in life. However, on multiple regression
      analyses, the only independent predictor of elderly suicide rates in males in
      both the elderly age-bands and in females in the age-band 65-74 years was the
      proportion of elderly in the total population. Conclusions. The mechanism through
      which adversity early in life and the proportion of elderly in the general
      population affect elderly suicide rates requires formal testing in long-term
      within-country longitudinal studies where adversity early in life changes over
      time within a country. 

PMID- 24916937
TI  - Factor analysis of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4)
      Chinese version and related factors.
AB  - Objectives. To validate the Schizophrenia Quality of Life Scale Revision 4 (SQLS
      R4) Chinese version with factor analysis. We also investigated factors
      influencing quality of life results. Method. One hundred patients with
      schizophrenia participated in this study. Experienced psychiatrists evaluated
      each patient's current psychological condition to assure intact judgment.
      Participants then filled out the quality of life questionnaire, SQLS-R4. We used
      principal component analysis to analyze SQLS-R4 with oblique rotation. We also
      collected demographic data, another subjective and objective quality of life
      questionnaire, and information about the functional status of the participants at
      the same time. Multiple linear regression was used to analyze collected factors
      which may influence the quality of life of schizophrenic patients. Results. We
      extracted seven factors that explained a 68.1% variance in the patients' quality
      of life. The factors were relationships with others, loneliness, exhaustion,
      depressed thinking, somatic concerns, vitality, and worry. Conclusion. We found
      that the SQLS-R4 factor analysis provided insights into the structure of the
      quality of life of patients with schizophrenia. We also found that subjective
      social participation, subjective health, and depression were quality-of-life
      related factors. Whether other factors influence the quality of life in patients
      with schizophrenia requires further investigation. 

PMID- 24916938
TI  - Population-attributable risk of childhood sexual abuse for symptoms of depression
      and suicidal ideation in adulthood.
AB  - Objective. The aim of the study was to assess the population-attributable risks
      (PAR) of childhood sexual abuse (CSA) for depressive symptoms and suicidal
      ideation in adulthood. Method. A total of 2501 adult participants were randomly
      recruited and interviewed using a computer-assisted telephone interviewing
      system. They responded to items designed to assess depressive symptoms (SF-12),
      suicidal ideation (GHQ-28), and other distressing events, including CSA, as part
      of a broader, mental health survey of the South Australian population. Results.
      Logistic regression analyses indicated that CSA was associated with both
      depressive symptoms and suicidal ideation. However, PAR estimates indicated that
      only 0.8% of depressive symptoms could be attributed to CSA. Similarly, only 2.2%
      of suicidal ideation in the population could be attributed to CSA. Conclusions.
      Notwithstanding the individual distress associated with CSA, a population
      perspective indicated that the impact of CSA in adulthood was not as great as one
      might interpret from media reports. 

PMID- 24916939
TI  - Investigation of attention deficit and hyperactivity disorder in adult patients
      with atopic dermatitis.
AB  - Background. Atopic dermatitis (AD) is a common chronic inflammatory disease that
      is associated with significant psychosocial morbidity and a decrease in health
      related quality of life. Attention deficit hyperactivity disorder may be present
      in atopic dermatitis patients. Objective. The present study aims to investigate
      the co-presence of ADHD in adult patients with AD. Material and method. The study
      registered 60 adult patients with AD (48 females and 12 males) and 50 non-atopic
      control subjects (38 females and 12 males). The AD patient group and the control
      group were assessed using the Turgay adult Attention-Deficit/Hyperactivity
      Disorder (ADD/ADHD) DSM-IV-Based Diagnostic Screening and Rating Scale (Turkish
      Version), which was studied by a team of psychologists and psychiatrists in
      Turkey for validity, reliability and norms. The scale covers three dimensions of
      the disease, namely inattention, hyperactivity and impulsivity, and associated
      features of ADHD. The groups were compared and contrasted in terms of their
      similarities and differences in ADD/ADHD symptoms. Results. Three sub-dimensions
      of ADD/ADHD scale (Attention Deficit, Hyperactivity/ Impulsivity and Problem
      subdivisions) in AD patients were found statistically significantly elevated
      relative to controls (P<0.001, P<0.001, P<0.001, respectively). Conclusions. In
      conclusion we established the co-presence of ADHD in AD patients in the adult age
      group. 

PMID- 24916940
TI  - Risperidone long acting injection: Findings of a 2-year retrospective follow-up
      study.
AB  - Objective. The aim of this retrospective study was to assess the clinical
      effectiveness of risperidone long acting injection (RLAI) at 2 years within an
      acute mental health setting. Method. All patients who received RLAI between July
      2002 and December 2004 were identified from pharmacy records, and data collected
      by retrospective case note review. In order to give an indication that their
      condition was unresponsive to treatment, patients' drug histories were reviewed
      to determine whether or not they had previously been treated with clozapine or
      received two or more failed trials of other antipsychotic medication. Results.
      Eighty-four patients were included in the study and 56 discontinued at 2 years.
      The most common reason for treatment discontinuation was lack of effectiveness,
      accounting for 32 patients, whilst eight patients discontinued due to adverse
      effects. Patients remaining on treatment spent 67% of the time in an outpatient
      setting. Conclusion. The proportion of patients remaining on RLAI at 2 years was
      33%. Limitations of the naturalistic methodology used in this study hindered any
      precise determination of which patients were likely to continue RLAI. However, it
      was apparent that a history of previous treatment failure with at least two
      antipsychotics was associated with RLAI treatment discontinuation. 

PMID- 24916941
TI  - The reliability and validity of the Chinese version of the Modified Overt
      Aggression Scale.
AB  - Objective. Instruments to assess aggressive behaviors in the psychiatric ward are
      crucial for monitoring risky behaviors. The purpose of this study was to assess
      the validity and reliability of the Chinese version of the Modified Overt
      Aggression Scale (MOAS). Methods. We translated the English version of MOAS into
      Chinese. We interviewed and trained two volunteers to act as agitated patients in
      the seclusion room. One senior psychiatrist, experienced in using the MOAS,
      directed scenarios of different aggressive intensity and established the standard
      scores. The validity was assessed by comparing the other raters' scores with
      those of the director's. Inter-rater reliability was also assessed. Results.
      Inter-rater reliability, based on Intra-class correlation coefficient (ICC=0.94,
      P<0.001) and Kendall's W coefficient of concordance (W=0.83, P= 0.001), was high.
      The validity was assessed by the Mann-Whitney test. The results showed that the
      raters adequately differentiated (z=- 2.89, P= 0.002) between the above-average
      and below-average scores of the MOAS. Conclusion. The Chinese version of the MOAS
      has modest psychometric properties. The model, which used trained volunteers
      acting as patients and compared their scores with those of the director, may be
      used in further studies for developing psychometric instruments to assess abrupt
      behaviors. 

PMID- 24916942
TI  - Assessing and managing suicidal behaviour in the primary care setting: A model
      for an integrated regional suicide prevention strategy.
AB  - Although suicide rates are decreasing in most countries, suicide is still a major
      health concern. Our aim was to introduce a complex, integrative, regional suicide
      prevention strategy. Based on reviewing the literature and on our previous
      studies we developed a suicide prevention model, which includes recognition, risk
      assessment and intervention. The main steps of the model are the recognition of
      warning signs (communicative or behavioural), exploration of crisis situation
      and/or psychopathologic symptoms, assessment of protective and risk factors,
      estimation of suicide risk and a plan for management of suicidal patients through
      different levels of interventions. In the management of suicidal behaviour, the
      complex stress-diathesis model has to be adjusted by considering biological
      markers and psycho-social factors. Only after the assessment of these factors can
      primary care professionals, as gatekeepers, manage suicidal patients effectively
      by using adequate psychopharmacotherapeutic and psychotherapeutic interventions
      in the recognition, treatment and prevention of suicidal behaviour. 

PMID- 24916943
TI  - The prevalence of comorbid anxiety disorders in outpatients with schizophrenia.
AB  - Objective. The purpose of this study was to determine the prevalence of lifetime
      anxiety disorders in patients with schizophrenia in Sanliurfa, Turkey, and to
      assess the association between comorbidity and several demographic and clinical
      variables. Methods. Eighty-two outpatients diagnosed with schizophrenia were
      recruited for the study. They were assessed by means of the Structured Clinical
      Interview for DSM-IV axis I Disorders-Clinician Version (SCID-I-CV), Anxiety
      Disorder Module, the Positive and Negative Syndrome Scale (PANSS), the Hamilton
      Anxiety Rating Scale (HARS), and the Global Assessment of Functioning Scale
      (GAF). Results. Fifty-five (67.1%) were diagnosed with at least one lifetime
      comorbid anxiety disorder. The most common anxiety disorder was obsessive
      compulsive disorder (39.0%), followed by social phobia (13.4%). We found patients
      with a diagnosis of schizophrenia with comorbid anxiety disorders had shorter
      duration of illness than those without such comorbid conditions. Atypical
      antipsychotics were more commonly prescribed to treat these patients. Conclusion.
      As comorbidity of anxiety disorders is relatively prevalent among patients with a
      diagnosis of schizophrenia, special attention to this issue should be paid when
      interviewing these patients. 

PMID- 24916944
TI  - The association between children's ADHD subtype and parenting stress and parental
      symptoms.
AB  - Objective. To investigate the association between two attention
      deficit/hyperactivity disorder (ADHD) subtypes-combined and inattentive subtypes
      and parental stress in a Taiwanese population. Method. One hundred and nine
      children with ADHD were interviewed using the MINI Kid questionnaire. The
      children were divided into combined and inattentive subtypes. The level of
      parenting stress was measured with the self-report Parenting Stress Index and
      Parental Symptom Scale (Symptom Check List, SCL-90). The data were used to
      identify child and parental risk factors. Results. Combined subtype was highly
      associated with parental stress. Parents of children in this group were
      significantly younger, had a poorer understanding of ADHD, and had significantly
      higher levels of marital discord, parenting stress, parental symptoms, and life
      stress (all P<0.05). Multivariate analysis revealed that age of mother, child
      with comorbidity diagnosis, and parents with poor understanding of ADHD were
      significantly associated with the combined subtype relative to inattentive
      subtype (all P<0.05). Conclusion. The combined subtype of ADHD is associated with
      more parental psychopathology and stress than the inattentive subtype and the
      presence of combined subtype may indicate that such a child is at greater risk
      than the inattentive subtype for comorbid conditions such as oppositional defiant
      disorder and conduct disorder. 

PMID- 24916945
TI  - The forgotten caregivers: Siblings of schizophrenic patients.
AB  - Objective. The situation of caregivers of psychiatric patients is mostly focussed
      on burdens of parents or spouses of patients. The burden of siblings due to the
      illness, however, is mostly underestimated and disregarded. Methods. Thirty-seven
      narrative interviews with siblings of schizophrenia inpatients were analysed by
      using a summarizing content analysis. The founded global statements were
      quantitatively analysed. Regression-analysis as well as regression trees were
      used to evaluate the data linked with sociodemographic and disease-related
      variables of the patient and siblings. Results. The results showed a high
      proportion of siblings engaged in caregiving activities. A total of 492
      individual statements were summarized in 26 global types of statements. The three
      most often reported burdens by the healthy siblings are: "Handling the symptoms
      of illness" (100%), "Emotional burden due to the illness of the sibling" (100%)
      and "Uncertainty in judging what amount of stress the patient can cope with"
      (81.1%). Linear regression and regression tree analysis show predictors for
      higher burdened siblings. Conclusion. Siblings of schizophrenia patients are
      burdened in various aspects and in a specific matter. Their special needs will
      therefore have to be recognised before they can receive appropriate intervention.

PMID- 24916946
TI  - Psychophysiological disorders among buprenorphine patients.
AB  - In this study, we examined the prevalence of 14 psychophysiological disorders
      among 114 opioid-dependent individuals (a sample that previously evidenced high
      rates of borderline personality) as well as the relationship between these
      disorders and borderline personality. In the aftermath of analyses, only migraine
      headaches (28.9%) and chronic pain (33.3%) demonstrated relatively high frequency
      rates in this sample. Only migraine headaches showed a significant relationship
      with the diagnosis of borderline personality symptoms. In conclusion, in an
      opioid-dependent population, the prevalence of psychophysiological disorders
      appears to be rather unremarkable. 

PMID- 24916947
TI  - Childhood trauma and sexual behavior in adulthood among internal medicine
      outpatients.
AB  - Abuse in childhood may be associated with a variety of sexual behaviors in
      adulthood. However, previous studies have been limited by population type, number
      of traumas inquired about, and number of sexual behaviors explored. In this
      study, we examined five forms of childhood abuse or trauma (i.e. sexual abuse,
      physical abuse, emotional abuse, physical neglect, and the witnessing of
      violence) and 13 sexuality variables (e.g., age at first intercourse, number of
      different sexual partners) among 76 women in an outpatient resident-provider
      internal medicine setting. Participants who had experienced childhood "sexual
      abuse" reported a younger "age at first intercourse" and a greater incidence of
      having "ever been raped by a stranger" and having "ever been raped by a partner" 
      but not multiple sexual partners (i.e. promiscuity), as expected. We discuss the
      implications of these findings. 

PMID- 24916949
TI  - AMP-activated protein kinase is required for cell survival and growth in HeLa-S3
      cells in vivo.
AB  - Activation of the AMP-dependent protein kinase (AMPK) is linked to cancer cell
      survival in a variety of cancer cell lines, particularly under conditions of
      stress. As a potent activator of AMPK, metformin has become a hot topic of
      discussion for its effect on cancer cell. Here, we report that AMPK activated by
      metformin promotes HeLa-S3 cell survival and growth in vivo. Our results show
      that metformin inhibited cell proliferation in MCF-7 cells, but not in LKB1
      deficient HeLa-S3 cells. Re-expression of LKB-1 in HeLa-S3 cells restored the
      growth inhibitory effect of metformin, indicating a requirement for LKB-1 in
      metformin-induced growth inhibition. Moreover, AMPK activation exerted a
      protective effect in HeLa-S3 cells by relieving ER stress, modulating ER Ca(2+)
      storage, and finally contributing to cellular adaptation and resistance to
      apoptosis. Our findings identify a link between AMPK activation and cell survival
      in HeLa-S3 cells, which demonstrates a beneficial effect of AMPK activated by
      metformin in cancer cell, and suggests a discrete re-evaluation on the role of
      metformin/AMPK activation on tumor cell growth, proliferation, and on clinical
      application in cancer therapy.

PMID- 24916950
TI  - Optimization of HPV DNA detection in urine by improving collection, storage, and
      extraction.
AB  - The benefits of using urine for the detection of human papillomavirus (HPV) DNA
      have been evaluated in disease surveillance, epidemiological studies, and
      screening for cervical cancers in specific subgroups. HPV DNA testing in urine is
      being considered for important purposes, notably the monitoring of HPV
      vaccination in adolescent girls and young women who do not wish to have a vaginal
      examination. The need to optimize and standardize sampling, storage, and
      processing has been reported.In this paper, we examined the impact of a DNA
      conservation buffer, the extraction method, and urine sampling on the detection
      of HPV DNA and human DNA in urine provided by 44 women with a cytologically
      normal but HPV DNA-positive cervical sample. Ten women provided first-void and
      midstream urine samples. DNA analysis was performed using real-time PCR to allow
      quantification of HPV and human DNA.The results showed that an optimized method
      for HPV DNA detection in urine should (a) prevent DNA degradation during
      extraction and storage, (b) recover cell-free HPV DNA in addition to cell
      associated DNA, (c) process a sufficient volume of urine, and (d) use a first
      void sample.In addition, we found that detectable human DNA in urine may not be a
      good internal control for sample validity. HPV prevalence data that are based on
      urine samples collected, stored, and/or processed under suboptimal conditions may
      underestimate infection rates. 

PMID- 24916951
TI  - Inflammation and psychosocial factors mediate exercise effects on sleep quality
      in breast cancer survivors: pilot randomized controlled trial.
AB  - OBJECTIVE: To improve mechanistic understanding, this pilot randomized controlled
      trial examined mediators of an exercise intervention effects on sleep in breast
      cancer survivors (BCS). METHODS: Forty-six postmenopausal BCS (<=Stage II, off
      primary treatment) were randomized to a 3-month exercise intervention or control
      group. Intervention included 160 min/week of moderate intensity aerobic walking,
      twice weekly resistance training (resistance bands), and six discussion groups
      (to improve adherence). Blinded assessments at baseline and post-intervention
      included sleep disturbance (PSQI and PROMIS(r)), objective sleep quality
      (accelerometer), serum cytokines, accelerometer physical activity,
      cardiorespiratory fitness, body composition, fatigue, and psychosocial factors.
      Mediation was tested using Freedman-Schatzkin difference-in-coefficients tests.
      RESULTS: When compared with control, the intervention group demonstrated a
      significant increase in PSQI sleep duration (i.e., fewer hours of sleep/night) (d
      = 0.73, p = .03). Medium to large but non-significant standardized effect sizes
      were noted for PSQI daytime somnolence (d = -0.63, p = .05) and accelerometer
      latency (d = -0.49, p = .14). No statistically significant mediators were
      detected for PSQI sleep duration score or accelerometer latency. Daytime
      somnolence was mediated by tumor necrosis factor-alpha (mediated 23% of
      intervention effect, p < .05), interleukin (IL)-6:IL-10 (16%, p < .01), IL-8:IL
      10 (26%, p < .01), and fatigue (38%, p < .05). Mediating or enhancing
      relationships for several of the sleep outcomes were noted for accelerometer
      physical activity, PROMIS(r) fatigue, exercise social support, and/or physical
      activity enjoyment. CONCLUSIONS: Inflammation and psychosocial factors may
      mediate or enhance sleep response to our exercise intervention. Further study is
      warranted to confirm our results and translate our findings into more effective
      interventions aimed at improving sleep quality in BCS.

PMID- 24916953
TI  - Randomized controlled trial of a prehospital decision system by emergency medical
      services to ensure optimal treatment for older adults in Sweden.
AB  - OBJECTIVES: To evaluate the feasibility and appropriateness of a prehospital
      system allowing ambulance nurses to transport older adults directly to geriatric
      care at a community-based hospital (CH) or to an emergency department (ED).
      DESIGN: Randomized controlled trial. SETTING: Emergency medical services in
      Stockholm, Sweden. PARTICIPANTS: Older adults who called the emergency number
      were randomized to an intervention group (n = 410) or a control group (n = 396).
      INTERVENTION: The dispatcher randomized the individuals. Those randomized to the
      intervention group were transported to several alternative destinations decided
      by a trained nurse performing a comprehensive assessment, using the new
      prehospital system. Those randomized to the control group were transported to the
      ED. MEASUREMENTS: Primary endpoint: number of individuals triaged directly to a
      CH (feasibility). Secondary endpoint: number of subsequent transfers
      (appropriateness) from CH to ED within 24 hours after initial admission. RESULTS:
      After exclusion and crossover, the control group consisted of 217 and the
      intervention group of 449 older adults. The nurse sent 20% of the intervention
      group (90/449) (95% confidence interval (CI) = 16.6-24.0) directly to the CH when
      using the prehospital system. Six of those individuals (6.7%) (95% CI = 3.1-13.8)
      were subsequently transferred from the CH to the ED. Overall, the nurse
      appropriately triaged 93.3% of the participants (84/90) and transferred them to
      the CH, avoiding an ED visit. CONCLUSION: Ambulance nurses are able to send older
      adults to an alternative healthcare facility with the help of a prehospital
      decision support system. In this geographical setting, this appears to be a
      promising method to optimize resources and improve emergency care of elderly
      adults.

PMID- 24916952
TI  - Construction and immunogenicity of a DNA vaccine coexpressing GP3 and GP5 of
      genotype-I porcine reproductive and respiratory syndrome virus.
AB  - BACKGROUND: The European (EU) genotype of porcine reproductive and respiratory
      syndrome virus (Genotype-I PRRSV) has recently emerged in China. The coexistence
      of Genotype-I and -II PRRSV strains could cause seriously affect PRRSV diagnosis
      and management. Current vaccines are not able to protect against PRRSV infection
      completely and have inherent drawbacks. Thus, genetically engineered vaccines,
      including DNA vaccine and live vector engineered vaccines, have been developed.
      This study aimed to determine the enhanced immune responses of mice inoculated
      with a DNA vaccine coexpressing GP3 and GP5 of a Genotype-I PRRSV. RESULTS: To
      evaluate the immunogenicity of GP3 and GP5 proteins from European-type PRRSV,
      three DNA vaccines, pVAX1-EU-ORF3-ORF5, pVAX1-EU-ORF3 and pVAX1-EU-ORF5, were
      constructed, which were based on a Genotype-I LV strain (GenBank ID: M96262).
      BALB/c mice were immunized with the DNA vaccines; delivered in the form of
      chitosan-DNA nanoparticles. To increase the efficiency of the vaccine, Quil A
      (Quillaja) was used as an adjuvant. GP3 and GP5-specific antibodies, neutralizing
      antibodies and cytokines (IL-2, IL-4, IL-10 and IFN gamma) from the immunized
      mice sera, and other immune parameters, were examined, including T-cell
      proliferation responses and subgroups of spleen T-lymphocytes. The results showed
      that ORF3 and ORF5 proteins of Genotype-I PRRSV induced GP3 and GP5-specific
      antibodies that could neutralize the virus. The levels of Cytokines IL-2, IL-4,
      IL-10, and IFN-gamma of the experimental groups were significantly higher than
      those of control groups after booster vaccination (P < 0.05). The production of
      CD3+CD4+ and CD3+CD8+ T lymphocyte was also induced. T lymphocyte proliferation
      assays showed that the PRRSV LV strain virus could stimulate the proliferation of
      T lymphocytes in mice in the experimental group. CONCLUSIONS: Using Quil A as
      adjuvant, Genotype-I PRRSV GP3 and GP5 proteins produced good immunogenicity and
      reactivity. More importantly, better PRRSV-specific neutralizing antibody titers
      and cell-mediated immune responses were observed in mice immunized with the DNA
      vaccine co-expressing GP3 and GP5 proteins than in mice immunized with a DNA
      vaccine expressing either protein singly. The results of this study demonstrated
      that co-immunization with GP3 and GP5 produced a better immune response in mice.

PMID- 24916954
TI  - A randomized controlled study of manikin simulator fidelity on neonatal
      resuscitation program learning outcomes.
AB  - The neonatal resuscitation program (NRP) has been developed to educate physicians
      and other health care providers about newborn resuscitation and has been shown to
      improve neonatal resuscitation skills. Simulation-based training is recommended
      as an effective modality for instructing neonatal resuscitation and both low and
      high-fidelity manikin simulators are used. There is limited research that has
      compared the effect of low and high-fidelity manikin simulators for NRP learning
      outcomes, and more specifically on teamwork performance and confidence. The
      purpose of this study was to examine the effect of using low versus high-fidelity
      manikin simulators in NRP instruction. A randomized posttest-only control group
      study design was conducted. Third year undergraduate medical students
      participated in NRP instruction and were assigned to an experimental group (high
      fidelity manikin simulator) or control group (low-fidelity manikin simulator).
      Integrated skills station (megacode) performance, participant satisfaction,
      confidence and teamwork behaviour scores were compared between the study groups.
      Participants in the high-fidelity manikin simulator instructional group reported
      significantly higher total scores in overall satisfaction (p = 0.001) and
      confidence (p = 0.001). There were no significant differences in teamwork
      behaviour scores, as observed by two independent raters, nor differences on
      mandatory integrated skills station performance items at the p < 0.05 level.
      Medical students' reported greater satisfaction and confidence with high-fidelity
      manikin simulators, but did not demonstrate overall significantly improved
      teamwork or integrated skills station performance. Low and high-fidelity manikin
      simulators facilitate similar levels of objectively measured NRP outcomes for
      integrated skills station and teamwork performance. 

PMID- 24916955
TI  - The impact of 2011 ACGME duty hour restrictions on internal medicine resident
      workload and education.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) implemented work
      hour restrictions for physicians in training in 2003 that were revised July 1,
      2011. Current published data are insufficient to assess whether such work hour
      restrictions will have long-term impact on residents' education. We searched
      computer-generated reports of hospital in-patient census, continuity clinic
      census, in-training exam scores and first-year resident attendance at educational
      conferences for the academic years 2010-2011 (August 1, 2010-May 31, 2011) and
      2011-2013 (August 1, 2011-May 31, 2013). During the first year of the study
      period, the residents' inpatient internal medicine services admitted 1,754
      patients; during this same period for academic years 2011-2012 and 2012-2013, the
      teaching services admitted 1,539 and 1,428 patients respectively, yielding a
      decrease of 16.4%. Monthly, these services cared for a mean of 27.1 (27.1/175.4
      [15.4%]) fewer patients and 9.7 (9.7/34.4 [28.2%]) fewer patients per intern than
      in the previous year. No statistical difference was observed regarding continuity
      clinic attendance and in-training exam scores. Residents in the years following
      work hours restrictions attended more educational conferences. Implementation of
      2011 ACGME work hour regulations resulted in fewer patients seen by first-year
      residents in hospital, but did not affect in-training exam scores. Whether these
      findings will translate into differences in patient outcomes, and quality of care
      remains to be seen.

PMID- 24916956
TI  - Mammary tumour development is dose-dependently inhibited by n-3 polyunsaturated
      fatty acids in the MMTV-neu(ndl)-YD5 transgenic mouse model.
AB  - BACKGROUND: Breast cancer is attributable to modifiable risk factors including
      the intake of dietary n-3 polyunsaturated fatty acids (PUFA). A key piece of
      evidence, yet to be addressed, that would demonstrate a causal relationship
      between n-3 PUFA and breast cancer, is a dose-dependent effect of n-3 PUFA on
      tumour outcomes. Thus, the objective of the present study was to determine
      whether n-3 PUFA reduces mammary gland tumor outcomes in a dose-dependent manner
      in female MMTV-neu(ndl)-YD5 transgenic mice, an aggressive model of human breast
      cancer. METHODS: Harems were provided one of three experimental diets comprised
      of 0, 3 or 9% (w/w) menhaden fish oil containing n-3 PUFA. Female offspring were
      weaned onto the same parental diet and maintained on their respective diet for 20
      weeks. Tumour onset, size and multiplicity were measured throughout the study.
      Fatty acid composition of mammary gland and tumours were determined by gas-liquid
      chromatography. RESULTS: Tumour size was significantly (p < 0.05) reduced in a
      dose-dependent manner. n-3 PUFA were also incorporated in a dose-dependent
      manner; differential incorporation was observed for eicosapentaenoic and
      docosapentaenoic acids into mammary gland tissue, while docosahexaenoic acid was
      preferentially incorporated into tumours. CONCLUSION: Overall, the present study
      provides fundamental knowledge about the dose-dependent effect of n-3 PUFA on
      tumour outcomes in a pre-clinical model and also sheds light on the differential
      role of individual n-3 PUFA on tumour outcomes.

PMID- 24916957
TI  - Expression of orexins and their precursor in the porcine ovary and the influence
      of orexins on ovarian steroidogenesis in pigs.
AB  - Orexins A and B are hypothalamic neuropeptides associated with homeostasis and
      the reproductive system. The aim of the study was to compare the expression of
      the prepro-orexin gene and the intensity of orexins immunoreactivity in the
      porcine ovary (corpora lutea, granulosa and theca interna cells) during four
      different stages of the oestrous cycle (days: 2-3, 10-12, 14-16 and 17-19) and to
      examine the in vitro effect of orexins on the secretion of steroid hormones by
      porcine luteal, granulosa and theca interna cells. The highest expression of
      prepro-orexin mRNA was observed in theca interna cells on days 17-19 of the
      oestrous cycle. The highest content of immunoreactive orexin A was noted in
      corpora lutea on days 10-12 and the highest level of immunoreactive orexin B on
      days 14-16 of the cycle. Immunoreactive orexin A concentrations were higher in
      theca interna cells than in granulosa cells, whereas similar levels of
      immunoreactive orexin B were observed in both cell types. Under in vitro
      conditions, at the concentration of 10 nM, orexins A and B inhibited FSH-induced
      oestradiol secretion by granulosa cells. The obtained results suggest that the
      pattern of orexin peptide expression in the porcine ovary is related to the
      animals' hormonal status. Our findings imply that orexins can affect porcine
      reproductive functions through modulation of ovarian steroidogenesis.

PMID- 24916959
TI  - World Cup 2014: festival of football or alcohol?

PMID- 24916958
TI  - RsaM: a transcriptional regulator of Burkholderia spp. with novel fold.
AB  - Burkholderia cepacia complex is a set of closely related bacterial species that
      are notorious pathogens of cystic fibrosis patients, responsible for life
      threatening lung infections. Expression of several virulence factors of
      Burkholderia cepacia complex is controlled by a mechanism known as quorum sensing
      (QS). QS is a means of bacterial communication used to coordinate gene expression
      in a cell-density-dependent manner. The system involves the production of
      diffusible signaling molecules (N-acyl-l-homoserine lactones, AHLs), that bind to
      cognate transcriptional regulators and influence their ability to regulate gene
      expression. One such system that is highly conserved in Burkholderia cepacia
      complex consists of CepI and CepR. CepI is AHL synthase, whereas CepR is an AHL
      dependent transcription factor. In most members of the Burkholderia cepacia
      complex group, the cepI and cepR genes are divergently transcribed and separated
      by additional genes. One of them, bcam1869, encodes the BcRsaM protein, which was
      recently postulated to modulate the abundance or activity of CepI or CepR. Here,
      we show the crystal structure of BcRsaM from B. cenocepacia J2315. It is a single
      domain protein with unique topology and presents a novel fold. The protein is a
      dimer in the crystal and in solution. This regulator has no known DNA-binding
      motifs and direct binding of BcRsaM to the cepI promoter could not be detected in
      in vitro assays. Therefore, we propose that the modulatory action of RsaM might
      result from interactions with other components of the QS machinery rather than
      from direct association with the DNA promoter. DATABASE: The atomic coordinates
      and structure factors have been deposited in the Protein Data Bank under entry
      4O2H. STRUCTURED DIGITAL ABSTRACT: BcRsaM and BcRsaM bind by x-ray
      crystallography (View interaction) BcRsaM and BcRsaM bind by molecular sieving
      (View interaction).

PMID- 24916961
TI  - Co-administration of creatine plus pyruvate prevents the effects of phenylalanine
      administration to female rats during pregnancy and lactation on enzymes activity
      of energy metabolism in cerebral cortex and hippocampus of the offspring.
AB  - Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is
      caused by deficiency in the activity of phenylalanine hydroxylase, leading to
      accumulation of phenylalanine and its metabolites. Untreated maternal PKU or
      hyperphenylalaninemia may result in nonphenylketonuric offspring with low birth
      weight and neonatal sequelae, especially microcephaly and intellectual
      disability. The mechanisms underlying the neuropathology of brain injury in
      maternal PKU syndrome are poorly understood. In the present study, we evaluated
      the possible preventive effect of the co-administration of creatine plus pyruvate
      on the effects elicited by phenylalanine administration to female Wistar rats
      during pregnancy and lactation on some enzymes involved in the phosphoryltransfer
      network in the brain cortex and hippocampus of the offspring at 21 days of age.
      Phenylalanine administration provoked diminution of body, brain cortex an
      hippocampus weight and decrease of adenylate kinase, mitochondrial and cytosolic
      creatine kinase activities. Co-administration of creatine plus pyruvate was
      effective in the prevention of those alterations provoked by phenylalanine,
      suggesting that altered energy metabolism may be important in the pathophysiology
      of maternal PKU. If these alterations also occur in maternal PKU, it is possible
      that pyruvate and creatine supplementation to the phenylalanine-restricted diet
      might be beneficial to phenylketonuric mothers. 

PMID- 24916962
TI  - Genetic dynamics underlying phenotypic development of biomass yield in triticale.
AB  - BACKGROUND: The nature of dynamic traits with their phenotypic plasticity
      suggests that they are under the control of a dynamic genetic regulation. We
      employed a precision phenotyping platform to non-invasively assess biomass yield
      in a large mapping population of triticale at three developmental stages.
      RESULTS: Using multiple-line cross QTL mapping we identified QTL for each of
      these developmental stages which explained a considerable proportion of the
      genotypic variance. Some QTL were identified at each developmental stage and thus
      contribute to biomass yield throughout the studied developmental phases.
      Interestingly, we also observed QTL that were only identified for one or two of
      the developmental stages illustrating a temporal contribution of these QTL to the
      trait. In addition, epistatic QTL were detected and the epistatic interaction
      landscape was shown to dynamically change with developmental progression.
      CONCLUSIONS: In summary, our results reveal the temporal dynamics of the genetic
      architecture underlying biomass accumulation in triticale and emphasize the need
      for a temporal assessment of dynamic traits.

PMID- 24916963
TI  - Multiparametric MRI for prostate cancer: seeing is believing.

PMID- 24916964
TI  - Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate
      receptor encephalitis.
AB  - OBJECTIVE: A severe but treatable form of immune-mediated encephalitis is
      associated with antibodies in serum and cerebrospinal fluid (CSF) against the
      GluN1 subunit of the N-methyl-D-aspartate receptor (NMDAR). Prolonged exposure of
      hippocampal neurons to antibodies from patients with anti-NMDAR encephalitis
      caused a reversible decrease in the synaptic localization and function of NMDARs.
      However, acute effects of the antibodies, fate of the internalized receptors,
      type of neurons affected, and whether neurons develop compensatory homeostatic
      mechanisms were unknown and are the focus of this study. METHODS: Dissociated
      hippocampal neuron cultures and rodent brain sections were used for
      immunocytochemical, physiological, and molecular studies. RESULTS: Patient
      antibodies bind to NMDARs throughout the rodent brain, and decrease NMDAR cluster
      density in both excitatory and inhibitory hippocampal neurons. They rapidly
      increase the internalization rate of surface NMDAR clusters, independent of
      receptor activity. This internalization likely accounts for the observed decrease
      in NMDAR-mediated currents, as no evidence of direct blockade was detected. Once
      internalized, antibody-bound NMDARs traffic through both recycling endosomes and
      lysosomes, similar to pharmacologically induced NMDAR endocytosis. The antibodies
      are responsible for receptor internalization, as their depletion from CSF
      abrogates these effects in hippocampal neurons. We find that although anti-NMDAR
      antibodies do not induce compensatory changes in glutamate receptor gene
      expression, they cause a decrease in inhibitory synapse density onto excitatory
      hippocampal neurons. INTERPRETATION: Our data support an antibody-mediated
      mechanism of disease pathogenesis driven by immunoglobulin-induced receptor
      internalization. Antibody-mediated downregulation of surface NMDARs engages
      homeostatic synaptic plasticity mechanisms, which may inadvertently contribute to
      disease progression.

PMID- 24916965
TI  - The Activation of Reward Versus Relief Gambling Outcome Expectancies in Regular
      Gamblers: Relations to Gambling Motives.
AB  - Gambling outcome expectancies refer to the anticipated outcomes that gamblers
      expect will occur from gambling (i.e., learned memory associations between
      gambling cues, behavior, and outcomes). Unlike previous approaches to gambling
      outcome expectancies that have predominantly focused on the valence of outcome
      expectancies (positive vs. negative), the present study investigated two specific
      types of positive gambling outcome expectancies: reward and relief gambling
      outcome expectancies. Specifically, the primary purpose of the current research
      was to examine whether gambling prime exposure activates different types of
      positive gambling outcome expectancies in enhancement- versus coping-motivated
      gamblers. Fifty adult, community-recruited regular gamblers performed a reaction
      time (RT) task and completed a self-report expectancy scale, both designed to
      assess reward and relief gambling outcome expectancies. They also completed the
      Gambling Motives Questionnaire (Stewart and Zack in Addiction 103:1110-1117 2008)
      to assess their levels of coping and enhancement motives for gambling. As
      hypothesized, reward gambling outcome expectancies were more strongly activated
      by gambling prime exposure than relief outcome expectancies on the RT task for
      gamblers with high enhancement motives. On the self-report expectancy measure,
      high enhancement-motivated gamblers endorsed stronger reward gambling outcome
      expectancies than low enhancement-motivated gamblers, and high coping-motivated
      gamblers endorsed stronger relief gambling outcome expectancies than low coping
      motivated gamblers. Results suggest that automatic activation of reward gambling
      outcome expectancies is particularly strong for high enhancement-motivated
      gamblers. Possible reasons for the failure to observe an association between
      coping gambling motives and automatic relief gambling outcome expectancies are
      discussed. 

PMID- 24916967
TI  - Methodologic comparison of left ventricular stroke volumes in the early neonatal
      period by echocardiography.
AB  - Several methods for evaluating left ventricular stroke volume (SV) in neonates
      using echocardiography have been reported. However, no studies on methodologic
      comparison of SV with three-dimensional (3D) echocardiography are available. This
      is the first detailed report on a methodologic comparison of SV in the early
      neonatal period. The study group included 70 normal neonates (35 boys and 35
      girls). An iE33 echocardiograph and Q-LAB supplied by Philips Electronics were
      used to examine and calculate volumes. Comparisons of SV were performed using
      Teichholz (T), the velocity time integral (VTI), Pombo (P), modified Simpson
      (MS), and 3D methods with normal neonates who had no persistent ductus arteriosus
      less than 7 days after birth. The mean SVs were 33.7 mL/m(2) (T), 30.6 mL/m(2)
      (VTI), 22.0 mL/m(2) (P), 17.5 mL/m(2) (3D), and 14.9 mL/m(2) (MS) using Haycock's
      formula of body surface area. The stroke volumes differed significantly depending
      on the different methods. The correlation coefficient was highest between the MS
      and 3D methods. The SVs of the T and VTI methods were significantly greater than
      those previously reported, and it seemed inappropriate to evaluate volumes in
      neonates. The 3D and MS methods were appropriate for measuring SV in neonates
      during the early neonatal period.

PMID- 24916968
TI  - Progesterone receptor-dependent regulation of genes in the oviducts of female
      mice.
AB  - Oviducts play a critical role in gamete and embryo transport, as well as
      supporting early embryo development. Progesterone receptor (PGR) is a
      transcription factor highly expressed in oviductal cells, while its activating
      ligand, progesterone, surges to peak levels as ovulation approaches. Progesterone
      is known to regulate oviduct cilia beating and muscular contractions in vitro,
      but how PGR may mediate this in vivo is poorly understood. We used PGR null mice
      to identify genes potentially regulated by PGR in the oviducts during the
      periovulatory period. Histologically, oviducts from PGR null mice showed no gross
      structural or morphological defects compared with normal littermates. However,
      microarray analysis of oviducts at 8 h posthuman chorionic gonadotropin revealed
      >1,000 PGR-dependent genes. Using reverse-transcription polymerase chain reaction
      (RT-PCR) we selected 10 genes for validation based on their potential roles in
      oocyte/embryo transport and support. Eight genes were confirmed to be
      downregulated (Adamts1, Itga8, Edn3, Prlr, Ptgfr, Des, Myocd, and Actg2) and one
      upregulated (Agtr2) in PGR null oviducts. Expression of these genes was also
      assessed in oviducts of naturally cycling mice during ovulation and day 1 and day
      4 of pregnancy. Adamts1, Itga8, Edn3, Prlr, and Ptgfr were significantly
      upregulated in oviducts at ovulation/mating. However, most genes showed basal
      levels of expression at other times. The exceptions were Prlr and Ptgfr, which
      showed pulsatile increases on day 1 and/or day 4 of pregnancy. This is the first,
      comprehensive study to elucidate putative PGR-regulated genes in the oviduct and
      reveals key downstream targets potentially mediating oocyte and embryo transport.

PMID- 24916969
TI  - Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year
      follow-up in normal weight and overweight children: the PANIC Study.
AB  - OBJECTIVES: PNPLA3 I148M polymorphism (rs738409) has been strongly associated
      with liver fat content and plasma alanine aminotransferase (ALT) levels in obese
      adults and children, but little is known about these relationships in normal
      weight individuals. We studied the associations and interactions of overweight
      and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up
      in children. METHODS: Subjects were a population sample of 481 Caucasian children
      aged 6-8 years examined at baseline and 419 children re-examined after 2-year
      follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419
      children after 2-year follow-up were overweight. We assessed plasma ALT levels
      and other cardiometabolic risk factors and genotyped the PNPLA3 I148M
      polymorphism. RESULTS: Being overweight and carrying PNPLA3 148M allele were
      associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after
      2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and
      carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT
      levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT
      levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P =
      0.002 for interaction) as well as a larger increase in ALT levels during 2-year
      follow-up (P = 0.002 for interaction) if they were overweight but not if they
      were normal weight. Further adjustment for clinical puberty, dietary factors,
      physical activity or sedentary behaviour had little or no effect on these
      associations. CONCLUSION: PNPLA3 148M allele carriers had higher plasma ALT
      levels and larger increase in ALT levels during follow-up than non-carriers only
      among overweight children.

PMID- 24916970
TI  - The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian
      cancer families of Portuguese ancestry.
AB  - We report the analysis of altogether 1050 suspected hereditary breast/ovarian
      cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526
      tested only for the most common mutations. Of the 119 families with pathogenic
      mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%)
      the BRCA1 c.3331_3334del mutation, the former being specific of Portuguese
      ancestry and the latter showing a founder effect in Portugal. Interestingly, the
      two most common mutations were found in a significant proportion of the HBOC
      families with an a priori BRCAPRO mutation probability <10%. We recommend that
      all suspected HBOC families from Portugal or with Portuguese ancestry, even those
      fulfilling moderately stringent clinical-criteria for genetic testing, should be
      specifically analyzed for the two most common BRCA1/BRCA2 founder mutations, and
      we here present a simple method for this first tier test. Screening of the entire
      coding regions of BRCA1 and BRCA2 should subsequently be offered to those
      families with a mutation probability >=10% if none of those founder mutations are
      found. 

PMID- 24916971
TI  - Transcriptome and methylome profiling reveals relics of genome dominance in the
      mesopolyploid Brassica oleracea.
AB  - BACKGROUND: Brassica oleracea is a valuable vegetable species that has
      contributed to human health and nutrition for hundreds of years and comprises
      multiple distinct cultivar groups with diverse morphological and phytochemical
      attributes. In addition to this phenotypic wealth, B. oleracea offers unique
      insights into polyploid evolution, as it results from multiple ancestral
      polyploidy events and a final Brassiceae-specific triplication event. Further, B.
      oleracea represents one of the diploid genomes that formed the economically
      important allopolyploid oilseed, Brassica napus. A deeper understanding of B.
      oleracea genome architecture provides a foundation for crop improvement
      strategies throughout the Brassica genus. RESULTS: We generate an assembly
      representing 75% of the predicted B. oleracea genome using a hybrid
      Illumina/Roche 454 approach. Two dense genetic maps are generated to anchor
      almost 92% of the assembled scaffolds to nine pseudo-chromosomes. Over 50,000
      genes are annotated and 40% of the genome predicted to be repetitive, thus
      contributing to the increased genome size of B. oleracea compared to its close
      relative B. rapa. A snapshot of both the leaf transcriptome and methylome allows
      comparisons to be made across the triplicated sub-genomes, which resulted from
      the most recent Brassiceae-specific polyploidy event. CONCLUSIONS: Differential
      expression of the triplicated syntelogs and cytosine methylation levels across
      the sub-genomes suggest residual marks of the genome dominance that led to the
      current genome architecture. Although cytosine methylation does not correlate
      with individual gene dominance, the independent methylation patterns of
      triplicated copies suggest epigenetic mechanisms play a role in the functional
      diversification of duplicate genes.

PMID- 24916972
TI  - Novel H3K4me3 marks are enriched at human- and chimpanzee-specific cytogenetic
      structures.
AB  - Human and chimpanzee genomes are 98.8% identical within comparable sequences.
      However, they differ structurally in nine pericentric inversions, one fusion that
      originated human chromosome 2, and content and localization of heterochromatin
      and lineage-specific segmental duplications. The possible functional consequences
      of these cytogenetic and structural differences are not fully understood and
      their possible involvement in speciation remains unclear. We show that
      subtelomeric regions--regions that have a species-specific organization, are more
      divergent in sequence, and are enriched in genes and recombination hotspots--are
      significantly enriched for species-specific histone modifications that decorate
      transcription start sites in different tissues in both human and chimpanzee. The
      human lineage-specific chromosome 2 fusion point and ancestral centromere locus
      as well as chromosome 1 and 18 pericentric inversion breakpoints showed
      enrichment of human-specific H3K4me3 peaks in the prefrontal cortex. Our results
      reveal an association between plastic regions and potential novel regulatory
      elements.

PMID- 24916974
TI  - Impact of home-delivered meal programs on diet and nutrition among older adults:
      a review.
AB  - BACKGROUND: Poor diet quality and insufficient nutrient intake is of particular
      concern among older adults. The Older Americans Act of 1965 authorizes home
      delivered meal services to homebound individuals aged 60 years and older.
      OBJECTIVE: The purpose of this study was to review scientific evidence on the
      impact of home-delivered meal services on diet and nutrition among recipients.
      METHODS: Keyword and reference searches were conducted in Cochrane Library,
      Google Scholar, PubMed and Web of Science. Inclusion criteria included: study
      design (randomized controlled trials, cohort studies, pre-post studies, or cross
      sectional studies); main outcome (food and nutrient intakes); population (home
      delivered meal program participants); country (US); language (articles written in
      English); and article type (peer-reviewed publications or theses). RESULTS: Eight
      studies met the inclusion criteria, including two randomized controlled trial
      studies (from the same intervention), one cohort study, two pre-post studies, and
      three cross-sectional studies. All but two studies found home-delivered meal
      programs to significantly improve diet quality, increase nutrient intakes, and
      reduce food insecurity and nutritional risk among participants. Other beneficial
      outcomes include increased socialization opportunities, improvement in dietary
      adherence, and higher quality of life. CONCLUSIONS: Home-delivered meal programs
      improve diet quality and increase nutrient intakes among participants. These
      programs are also aligned with the federal cost-containment policy to rebalance
      long-term care away from nursing homes to home- and community-based services by
      helping older adults maintain independence and remain in their homes and
      communities as their health and functioning decline.

PMID- 24916973
TI  - Reconfiguration of nucleosome-depleted regions at distal regulatory elements
      accompanies DNA methylation of enhancers and insulators in cancer.
AB  - It is well established that cancer-associated epigenetic repression occurs
      concomitant with CpG island hypermethylation and loss of nucleosomes at
      promoters, but the role of nucleosome occupancy and epigenetic reprogramming at
      distal regulatory elements in cancer is still poorly understood. Here, we
      evaluate the scope of global epigenetic alterations at enhancers and insulator
      elements in prostate and breast cancer cells using simultaneous genome-wide
      mapping of DNA methylation and nucleosome occupancy (NOMe-seq). We find that the
      genomic location of nucleosome-depleted regions (NDRs) is mostly cell type
      specific and preferentially found at enhancers in normal cells. In cancer cells,
      however, we observe a global reconfiguration of NDRs at distal regulatory
      elements coupled with a substantial reorganization of the cancer methylome.
      Aberrant acquisition of nucleosomes at enhancer-associated NDRs is associated
      with hypermethylation and epigenetic silencing marks, and conversely, loss of
      nucleosomes with demethylation and epigenetic activation. Remarkably, we show
      that nucleosomes remain strongly organized and phased at many facultative distal
      regulatory elements, even in the absence of a NDR as an anchor. Finally, we find
      that key transcription factor (TF) binding sites also show extensive peripheral
      nucleosome phasing, suggesting the potential for TFs to organize NDRs genome-wide
      and contribute to deregulation of cancer epigenomes. Together, our findings
      suggest that "decommissioning" of NDRs and TFs at distal regulatory elements in
      cancer cells is accompanied by DNA hypermethylation susceptibility of enhancers
      and insulator elements, which in turn may contribute to an altered genome-wide
      architecture and epigenetic deregulation in malignancy. 

PMID- 24916975
TI  - Thoracic vertebral osteomyelitis: an unusual complication of Crohn's disease.
AB  - Vertebral osteomyelitis complicating Crohn's disease is a rare occurrence and
      mostly occurred in patients with Crohn's disease complicated by an abscess or
      fistulising disease. We report a case of thoracic vertebral osteomyelitis,
      occurring in a refractory Crohn's disease without contiguous abscess or fistula
      with the bowel. 

PMID- 24916976
TI  - Persistence of hepatitis B surface antigen in blood in a chronic haemodialysis
      patient following vaccination booster.
AB  - Patients receiving haemodialysis are at an increased risk of hepatitis B
      infection; regular screening for incident infection and vaccination of
      susceptible individuals is recommended. Haemodialysis patients often require
      repeated high-dose hepatitis B vaccination boosters because of impaired response.
      Since the hepatitis B surface antigen is used as an immunogenic agent for
      vaccination and as a marker of hepatitis B infection, it has occasionally been
      detected in the blood shortly after vaccine administration and can be mistaken
      for a new infection. These transient results, however, are unlikely to persist
      for longer than 14 days after vaccination. We report the case of a haemodialysis
      patient who tested weakly positive for hepatitis B surface antigen 52 days after
      a vaccine booster. This is the longest vaccine-induced antigenaemia described in
      the literature and indicates that vaccination can cause weakly positive hepatitis
      B surface antigen results for longer than previously reported.

PMID- 24916977
TI  - Treating enuresis in a patient with ADHD: application of a novel behavioural
      modification therapy.
AB  - We report the case of a 6-year-old patient diagnosed with attention-deficit
      hyperactivity disorder (ADHD) and comorbid enuresis disorder, who was treated
      with methylphenidate for the past 3 months and a novel behavioural modification
      therapy by using an application called 'Enuresis Trainer'. This therapeutic
      application is basically an interactive 'Bedwetting Calendar', based on
      traditional cognitive behavioural modification therapies and positive
      reinforcement systems. Enuresis is defined as the failure of voluntary control of
      the urethral sphincter. The prevalence of enuresis is 15-20% in the child
      population; however, children with ADHD had a 2.7 times higher incidence of
      nocturnal enuresis. Bedwetting is a common cause of isolation in children as well
      as loss of self-esteem and other psychological distress for the child and the
      family.

PMID- 24916978
TI  - Tophaceous calcium pyrophosphate dihydrate deposition disease of the knee
      mimicking an aggressive soft tissue tumour.
AB  - Calcium pyrophosphate crystal deposition disease (CPPD), previously pseudogout,
      is the second most common crystal arthropathy after gout. There is increased
      radiographic prevalence associated with age, trauma and several metabolic
      disorders. Tophaceous CPPD (T-CPPD) is a rare form of CPPD which, though non
      neoplastic, mimics a bone or soft tissue malignancy. T-CPPD usually presents as a
      mass in the temporomandibular joint and occasionally in the paraspinal tissues,
      but rarely in the joints of the extremities. We present an exceptionally rare
      case of T-CPPD that was subtle on plain radiography, presenting as a soft tissue
      mass in the knee joint. 

PMID- 24916979
TI  - Robotic-assisted laparoscopic repair of a vesicovaginal fistula: a time-consuming
      novelty or an effective tool?
AB  - Vesicovaginal fistulas are a rare complication of hysterectomy. When conservative
      therapy fails, vaginal or abdominal repair is necessary. A robotic-assisted
      laparoscopic approach can be a useful tool to repair complex fistulas. A 50-year
      old woman with a vesicovaginal fistula located at the top of the vagina, was
      treated with robotic-assisted laparoscopic repair. The fistula tissue was removed
      from the vaginal wall and bladder, and epiploic of the sigmoid was interposed in
      between. The total operation time was 104 min. The hospital stay was 3 days; no
      complications occurred. Cystography 6 weeks and 6 months postoperative confirmed
      a successful repair. A review of current literature is presented regarding the
      application of robotic assistance during this procedure. The presented case shows
      that robotic-assisted laparoscopic repair of a vesicovaginal fistula seems to be
      a feasible technique with promising results.

PMID- 24916980
TI  - Belly button piercings: a saving grace? A patent urachus presenting in a 17-year
      old girl.
AB  - We report the case of a 17-year-old girl who presented to the accident and
      emergency department with dysuria and foul smelling, bloody discharge from her
      umbilicus. The definitive diagnosis was that of a patent urachus, which is a
      fistulous communication between the bladder and the umbilicus, usually diagnosed
      in early infancy. The incidence of a patent urachus is approximately 1 in 70,000
      in the general population. It is highly likely that removal of a recent belly
      button piercing resulted in the acute presentation by completing the fistulous
      tract to the skin. This case is of clinical relevance as the diagnosis was missed
      18 months prior with a milder presentation. The recommended treatment option is
      surgical excision due to the potential risk of malignant change, with urachal
      adenocarcinoma accounting for 0.3% of all bladder cancers.

PMID- 24916981
TI  - Unusual panuveitis in a child: toxocariasis associated with ocular myiasis.
AB  - Most panuveitis in children are caused by infectious agents. A detailed clinical
      history and clinical examination are helpful in the diagnosis, but specific
      techniques are sometimes required to identify the causing specimen. We report the
      first published case of panuveitis in a child caused by simultaneous ocular
      infection by Toxocara canis and a fly larva and the innovative use of
      immunodiffusion technique in the vitreous for the diagnosis. 

PMID- 24916982
TI  - Successful treatment of Salmonella aortitis with endovascular aortic repair and
      antibiotic therapy.
AB  - We report a case of a 77-year-old Asian man with a history significant for type
      II diabetes mellitus and chronic kidney disease who presented with abdominal
      pain, nausea, vomiting and a 20-pound weight loss of 3 weeks' duration. Further
      evaluation revealed an infected mycotic aneurysm and distal abdominal aortitis as
      a result of Salmonella. This case demonstrates an interesting case of aortitis
      and a successful therapeutic approach.

PMID- 24916983
TI  - Where's the ulcer? Spontaneous bleeding from Zenker's diverticulum.
AB  - An 89-year-old man with a history of coronary artery disease status post coronary
      artery bypass grafting and atrial fibrillation on aspirin and warfarin, presented
      to the emergency department with a symptom of haemoptysis. He reported a history
      of dysphagia for 3 months prior to presentation, but had yet to seek medical
      attention. On presentation, he was hypotensive and tachycardic with a haemoglobin
      of 6.6 g/dL and an International Normalised Ratio (INR) of 3.9.
      Esophagogastroduodenoscopy was performed and showed active bleeding from Zenker's
      diverticulum. The patient's INR was reversed with fresh frozen plasma and his
      anaemia was treated with packed red blood cells. The bleeding stopped after
      reversal of his INR. A barium swallow confirmed a 9 cm Zenker's diverticulum. The
      patient had a diverticulectomy and cricopharyngeal myotomy. Histology showed mild
      chronic inflammation of the mucosa, but no ulceration. The patient was discharged
      without any further bleeding episodes.

PMID- 24916984
TI  - Three stripes sign: muscle involvement with internal fibrosis in a patient with
      sarcoidosis.

PMID- 24916985
TI  - Atypical cutaneous leishmaniasis in the immunosuppressed.
AB  - A 45-year-old woman, known case of seronegative arthritis and on
      immunosuppressive therapy, presented with a 2-week history of a macular lesion on
      the left calf that became papular and eventually ulcerated. The rest of the
      history was otherwise unremarkable and systemic examination did not reveal any
      abnormalities. The lesion was repeatedly biopsied but failed to reveal Leishmania
      donovani bodies. Concurrent Leishmania IgG was positive but IgM was negative.
      Leishmania IgG confirmatory testing by ELISA was negative. A biopsy from the
      lesion eventually tested positive for L. donovani through PCR. The patient was
      treated with sodium stibogluconate together with intravenous ciprofloxacin and
      amoxicillin to cover the secondary cutaneous bacterial infection. This led to
      complete resolution of the lesion. 

PMID- 24916986
TI  - Concurrent diffuse alveolar haemorrhage and venous thromboembolism in p-ANCA
      associated vasculitis treated with rituximab.

PMID- 24916987
TI  - Duchenne muscular dystrophy.

PMID- 24916988
TI  - Foreword: applied computational chemistry.

PMID- 24916989
TI  - Patient throughput benefits of triage liaison providers are lost in a resource
      neutral model: a prospective trial.
AB  - OBJECTIVES: Patient throughput is an increasingly important cause of emergency
      department (ED) crowding. The authors previously reported shorter patient length
      of stay (LOS) when adding a triage liaison provider, which required additional
      personnel. Here, the objective was to evaluate the effect of moving a fast-track
      provider to the triage liaison role. METHODS: This was a prospective
      observational before-and-after study design with predefined outcomes measures. A
      "standard staffing" situation (where an advanced practice provider staffed
      treatment rooms in the fast track) was compared with an advanced practice
      provider performing the triage liaison staffing role, with no additional staff.
      Eleven intervention ("triage liaison staffing") days were compared with 11
      matched control ("standard staffing") days immediately preceding the
      intervention. Total LOS was measured for all adult Emergency Severity Index (ESI)
      3, 4, and 5 patients (excluding behavioral health patients), and results were
      compared using Wilcoxon rank-sum and chi-square tests. RESULTS: A total of 681
      patients registered on control days and 599 on intervention days. There was no
      significant difference in total patient LOS: median = 273 minutes, interquartile
      range (IQR) 176 to 384 minutes on intervention days versus median = 253 minutes,
      IQR = 175 to 365 minutes on control days (p = 0.20). There was no difference in
      left-without-being-seen (LWBS) rates (n = 48, 7% on control days vs. n = 35, 6%
      on intervention days; p=0.38). Secondary analysis of only ESI 3 patients showed
      no difference in total LOS between periods (median = 284 minutes, IQR = 194 to
      396 minutes on intervention days vs. median = 290 minutes, IQR = 217 to 397
      minutes on control days; p = 0.22). There was, however, significantly greater
      total LOS for ESI 4 and 5 patients during the intervention period (median = 238
      minutes, IQR = 124 to 350 minutes on intervention days vs. median = 192 minutes,
      IQR = 124 to 256 minutes on control days; p = 0.011). CONCLUSIONS: The previously
      reported benefits on patient LOS and LWBS rates after adding a triage liaison
      (resource additive) were lost when that provider was moved from fast track to the
      triage role (resource neutral). While the triage liaison provider role may be a
      way to improve ED throughput when additional resources are available, as
      evidenced by our prior study, the triage liaison model itself does not appear to
      replace the staffing of treatment rooms, as evidenced by this study.

PMID- 24916990
TI  - Prospecting sugarcane resistance to Sugarcane yellow leaf virus by genome-wide
      association.
AB  - KEY MESSAGE: Using GWAS approaches, we detected independent resistant markers in
      sugarcane towards a vectored virus disease. Based on comparative genomics,
      several candidate genes potentially involved in virus/aphid/plant interactions
      were pinpointed. Yellow leaf of sugarcane is an emerging viral disease whose
      causal agent is a Polerovirus, the Sugarcane yellow leaf virus (SCYLV)
      transmitted by aphids. To identify quantitative trait loci controlling resistance
      to yellow leaf which are of direct relevance for breeding, we undertook a genome
      wide association study (GWAS) on a sugarcane cultivar panel (n = 189)
      representative of current breeding germplasm. This panel was fingerprinted with
      3,949 polymorphic markers (DArT and AFLP). The panel was phenotyped for SCYLV
      infection in leaves and stalks in two trials for two crop cycles, under natural
      disease pressure prevalent in Guadeloupe. Mixed linear models including co
      factors representing population structure fixed effects and pairwise kinship
      random effects provided an efficient control of the risk of inflated type-I error
      at a genome-wide level. Six independent markers were significantly detected in
      association with SCYLV resistance phenotype. These markers explained individually
      between 9 and 14 % of the disease variation of the cultivar panel. Their
      frequency in the panel was relatively low (8-20 %). Among them, two markers were
      detected repeatedly across the GWAS exercises based on the different disease
      resistance parameters. These two markers could be blasted on Sorghum bicolor
      genome and candidate genes potentially involved in plant-aphid or plant-virus
      interactions were localized in the vicinity of sorghum homologs of sugarcane
      markers. Our results illustrate the potential of GWAS approaches to prospect
      among sugarcane germplasm for accessions likely bearing resistance alleles of
      significant effect useful in breeding programs.

PMID- 24916991
TI  - A unique semiconductor-metal-graphene stack design to harness charge flow for
      photocatalysis.
AB  - A novel semiconductor-metal-graphene stack design, which reduces interfacial
      defect density as well as provides channels for charge transport, has been
      demonstrated to harness the charge flow for efficient electron-hole separation.
      As a direct outcome, the designed hybrid structures exhibit significantly
      improved performance in photocatalytic hydrogen production from water. 

PMID- 24916992
TI  - Influences of evergreen gymnosperm and deciduous angiosperm tree species on the
      functioning of temperate and boreal forests.
AB  - It has been recognized for a long time that the overstorey composition of a
      forest partly determines its biological and physical-chemical functioning. Here,
      we review evidence of the influence of evergreen gymnosperm (EG) tree species and
      deciduous angiosperm (DA) tree species on the water balance, physical-chemical
      soil properties and biogeochemical cycling of carbon and nutrients. We used
      scientific publications based on experimental designs where all species grew on
      the same parent material and initial soil, and were similar in stage of stand
      development, former land use and current management. We present the current state
      of the art, define knowledge gaps, and briefly discuss how selection of tree
      species can be used to mitigate pollution or enhance accumulation of stable
      organic carbon in the soil. The presence of EGs generally induces a lower rate of
      precipitation input into the soil than DAs, resulting in drier soil conditions
      and lower water discharge. Soil temperature is generally not different, or
      slightly lower, under an EG canopy compared to a DA canopy. Chemical properties,
      such as soil pH, can also be significantly modified by taxonomic groups of tree
      species. Biomass production is usually similar or lower in DA stands than in
      stands of EGs. Aboveground production of dead organic matter appears to be of the
      same order of magnitude between tree species groups growing on the same site.
      Some DAs induce more rapid decomposition of litter than EGs because of the
      chemical properties of their tissues, higher soil moisture and favourable
      conditions for earthworms. Forest floors consequently tend to be thicker in EG
      forests compared to DA forests. Many factors, such as litter lignin content,
      influence litter decomposition and it is difficult to identify specific litter
      quality parameters that distinguish litter decomposition rates of EGs from DAs.
      Although it has been suggested that DAs can result in higher accumulation of soil
      carbon stocks, evidence from field studies does not show any obvious trend.
      Further research is required to clarify if accumulation of carbon in soils (i.e.
      forest floor + mineral soil) is different between the two types of trees.
      Production of belowground dead organic matter appears to be of similar magnitude
      in DA and EG forests, and root decomposition rate lower under EGs than DAs.
      However there are some discrepancies and still are insufficient data about
      belowground pools and processes that require further research. Relatively larger
      amounts of nutrients enter the soil-plant biogeochemical cycle under the
      influence of EGs than DAs, but recycling of nutrients appears to be slightly
      enhanced by DAs. Understanding the mechanisms underlying forest ecosystem
      functioning is essential to predicting the consequences of the expected tree
      species migration under global change. This knowledge can also be used as a
      mitigation tool regarding carbon sequestration or management of surface waters
      because the type of tree species affects forest growth, carbon, water and
      nutrient cycling. 

PMID- 24916993
TI  - Wars versus SARS: Are epidemiological studies biased?

PMID- 24916995
TI  - Naturally and stimulated levels of reactive oxygen species in cooled stallion
      semen destined for artificial insemination.
AB  - The decrease in foaling rates after artificial insemination with cooled semen
      warrants the search for new predictors of fertility. The objectives were to
      investigate levels of naturally occurring reactive oxygen species (ROS) in
      cooled, stored stallion semen doses for artificial insemination (AI), and their
      relationship with parameters of semen quality and with pregnancy rate. Semen was
      collected from warmblood stallions (n=15) and used to prepare commercial semen
      doses for AI. Sperm quality was evaluated after cooled transport to the
      laboratory overnight. The results were correlated with observed foaling and
      pregnancy rates. Hydroethidine and dichlorodihydrofluorescein diacetate were used
      as indicators for the ROS superoxide and hydrogen peroxide, respectively. Sperm
      morphology, motility, plasma membrane integrity and chromatin integrity were also
      evaluated. These variables were correlated with each other and with pregnancy
      rates. We found a high inter-individual variation in the ROS levels between
      stallions. The proportion of live, hydrogen peroxide-negative spermatozoa was
      correlated with progressive motility, whereas live hydrogen peroxide-negative
      spermatozoa and chromatin damage were negatively correlated, indicating that low
      levels of hydrogen peroxide were correlated with good chromatin integrity. The
      percentage of dead hydrogen peroxide-positive sperm was negatively related to the
      foaling rate. The negative relationships were stronger when combining results
      from both assays for ROS. These results for stored semen samples indicate that
      high individual variation exists for superoxide and hydrogen peroxide
      measurements, and that ROS status can influence sperm quality. Thus, ROS may be
      some of the factors influencing fertility. Moreover, combinations of ROS
      variables improved the correlation with fertility, indicating the usefulness of
      including these variables in a future model for prediction of the fertility of a
      semen sample.

PMID- 24916994
TI  - Place of upbringing in early childhood as related to inflammatory bowel diseases
      in adulthood: a population-based cohort study in Northern Europe.
AB  - BACKGROUND: The two inflammatory bowel diseases (IBD), ulcerative colitis and
      Crohn's disease, has increased rapidly during the twentieth century, but the
      aetiology is still poorly understood. Impaired immunological competence due to
      decreasing biodiversity and altered microbial stimulation is a suggested
      explanation. OBJECTIVE: Place of upbringing was used as a proxy for the level and
      diversity of microbial stimulation to investigate the effects on the prevalence
      of IBD in adulthood. METHODS: Respiratory Health in Northern Europe (RHINE) III
      is a postal follow-up questionnaire of the European Community Respiratory Health
      Survey (ECRHS) cohorts established in 1989-1992. The study population was 10,864
      subjects born 1945-1971 in Denmark, Norway, Sweden, Iceland and Estonia, who
      responded to questionnaires in 2000-2002 and 2010-2012. Data were analysed in
      logistic and Cox regression models taking age, sex, smoking and body mass index
      into consideration. RESULTS: Being born and raised on a livestock farm the first
      5 years of life was associated with a lower risk of IBD compared to city living
      in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95
      % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical
      difference in this association. Furthermore, there was a significant trend
      comparing livestock farm living, village and city living (p < 0.01). Sub-analyses
      showed that the protective effect was only present among subjects born after 1952
      (OR 0.25, 95 % CI 0.11; 0.61). CONCLUSION: This study suggests a protective
      effect from livestock farm living in early childhood on the occurrence of IBD in
      adulthood, however only among subjects born after 1952. We speculate that lower
      microbial diversity is an explanation for the findings.

PMID- 24916996
TI  - Fraud in a population-based study of headache: prevention, detection and
      correction.
AB  - BACKGROUND: In medicine, research misconduct is historically associated with
      laboratory or pharmaceutical research, but the vulnerability of epidemiological
      surveys should be recognized. As these surveys underpin health policy and
      allocation of limited resources, misreporting can have far-reaching implications.
      We report how fraud in a nationwide headache survey occurred and how it was
      discovered and rectified before it could cause harm. METHODS: The context was a
      door-to-door survey to estimate the prevalence and burden of headache disorders
      in Pakistan. Data were collected from all four provinces of Pakistan by non
      medical interviewers and collated centrally. Measures to ensure data integrity
      were preventative, detective and corrective. We carefully selected and trained
      the interviewers, set rules of conduct and gave specific warnings regarding the
      consequences of falsification. We employed two-fold fraud detection methods:
      comparative data analysis, and face-to-face re-contact with randomly selected
      participants. When fabrication was detected, data shown to be unreliable were
      replaced by repeating the survey in new samples according to the original
      protocol. RESULTS: Comparative analysis of datasets from the regions revealed
      unfeasible prevalences and gender ratios in one (Multan). Data fabrication was
      suspected. During a surprise-visit to Multan, of a random sample of addresses
      selected for verification, all but one had been falsely reported. The data (from
      840 cases) were discarded, and the survey repeated with new interviewers. The new
      sample of 800 cases was demographically and diagnostically consistent with other
      regions. CONCLUSION: Fraud in community-based surveys is seldom reported, but no
      less likely to occur than in other fields of medical research. Measures should be
      put in place to prevent, detect and, where necessary, correct it. In this
      instance, had the data from Multan been pooled with those from other regions
      before analysis, a damaging fraud might have escaped notice.

PMID- 24916997
TI  - Investigating the sonophoresis effect on the permeation of diclofenac sodium
      using 3D skin equivalent.
AB  - Ultrasound temporally increases skin permeability by altering stratum corneum SC
      function (sonophoresis). The objective of this study was to evaluate the effect
      of variable ultrasound conditions on the permeation of diclofenac sodium DS with
      range of physicochemical properties through EpiDermTM. Permeation studies were
      carried out in vitro using Franz diffusion cell. HPLC method was used for the
      determination of the concentration of diclofenac sodium in receiving compartment.
      Parameters like ultrasound frequency, application time, amplitude, and mode of
      sonication and distance of ultrasound horn from skin were investigated, and the
      conditions where the maximum enhancement rate obtained were determined.
      Application of ultrasound enhanced permeation of diclofenac sodium across
      EpiDermTM by fivefolds. The most effective enhancing parameters were power
      sonication of 20kHz frequency, 20% amplitude at continuous mode for 5min. 

PMID- 24916998
TI  - Dissociation between running economy and running performance in elite Kenyan
      distance runners.
AB  - The purpose of this study was to investigate the relationship between running
      economy (RE) and performance in a homogenous group of competitive Kenyan distance
      runners. Maximal aerobic capacity (VO2max) (68.8 +/- 3.8 ml?kg(-1)?min(-1)) was
      determined on a motorised treadmill in 32 Kenyan (25.3 +/- 5.0 years; IAAF
      performance score: 993 +/- 77 p) distance runners. Leg anthropometry was assessed
      and moment arm of the Achilles tendon determined. While Achilles moment arm was
      associated with better RE (r(2) = 0.30, P = 0.003) and upper leg length, total
      leg length and total leg length to body height ratio were correlated with running
      performance (r = 0.42, P = 0.025; r = 0.40, P = 0.030 and r = 0.38, P = 0.043,
      respectively), RE and maximal time on treadmill (t(max)) were not associated with
      running performance (r = -0.01, P = 0.965; r = 0.27; P = 0.189, respectively) in
      competitive Kenyan distance runners. The dissociation between RE and running
      performance in this homogenous group of runners would suggest that RE can be
      compensated by other factors to maintain high performance levels and is in line
      with the idea that RE is only one of many factors explaining elite running
      performance.

PMID- 24916999
TI  - [Treatment strategy for activating EGFR-mutated non-small cell lung cancer after
      failure of first-generation EGFR-TKIs].
AB  - Somatic activating mutations such as a deletion in exon 19 or the missense
      mutation L858R in the tyrosine kinase domain of the epidermal growth factor
      receptor(EGFR)are important mediators of cancer cell oncogenesis, proliferation,
      and survival. In the last decade, two EGFR target agents have significantly
      contributed to the understanding of non-small cell lung cancer (NSCLC). Gefitinib
      and erlotinib are first-generation EGFR-tyrosine kinase inhibitors(EGFR-TKIs)that
      play a key role in activating EGFR-mutated NSCLC. Although these reversible,
      small, molecular target agents provide a significant response and survival
      benefit, all responders eventually acquire resistance. Although various
      mechanisms of resistance have been identified, nearly 3 0% of patients who
      acquire resistance to EGFR-TKIs have an unknown mechanism of resistance.
      Approximately half the patients with EGFR-mutated NSCLC who develop acquired
      resistance to these molecular target agents have a secondary mutation T790M in
      the threonine gatekeeper residue that coexists with a primary EGFR activating
      mutation. The strategy for overcoming acquired resistance to first-generation
      EGFR-TKIs is a major clinical concept. Afatinib is a second-generation EGFR
      targeting agent and an irreversible pan-HER inhibitor. It may improve survival
      further and help in potentially overcoming resistance to first-generation EGFR
      TKIs in EGFR-mutated NSCLC. In patients harboring activating EGFR mutations,
      certain treatments could be suggested for subsequent therapy after failure of
      first-generation EGFR-TKIs. This review discusses novel therapeutic strategies
      for activating EGFR-mutated, advanced NSCLC after failure of first-generation
      EGFR-TKIs.

PMID- 24917000
TI  - [Cancer screening in Japan and prostate cancer screening].
AB  - National cancer control programs are structured to include four main areas:
      prevention, screening, diagnosis and treatment, and palliative care. Cancer
      screening is particularly important because it helps to reduce medical costs and
      achieve maximum benefits for both patients and the country. There are many issues
      with cancer screening in Japan that need a solution, such as low participation
      rate and lack of sufficient quality control. Prostate cancer screening frequently
      leads to over-diagnosis and over-treatment, and therefore it should not be part
      of the 6th national screening program in Japan.

PMID- 24917001
TI  - [Future perspectives on screening for prostate cancer - an experienced
      Urologist's viewpoint].
AB  - Recently, large prospective randomized controlled trials, the European Randomized
      Study of Screening for Prostate Cancer (ERSPC)and the Goteborg study, revealed
      that prostate specific antigen(PSA)-based screening can reduce mortality due to
      prostate cancer. In the Goteborg study, the reduction in mortality in the
      screening group during the median 14 years of follow-up was very high at 44%,
      based on intention-to-screen analysis. The merits of introducing PSA-based
      screening could be mortality reduction and prevention of progression to
      metastatic disease, which could decrease patient quality of life (QOL).
      Furthermore, the impact of screening for prostate cancer on mortality reduction
      was not inferior to that of the other population- based cancer screening program
      conducted in Japan, at the least. Therefore, PSA-based screening should be
      undertaken both as part of population-based screening and as part of
      opportunistic screening in Japan. However, as disadvantages, some participants in
      the screening program might be at risk of over detection and overtreatment.
      Therefore, providing a fact sheet for prostate cancer screening and an optimal
      screening system with more accurate detection methods, minimally invasive
      treatment, and an active surveillance strategy, which minimizes over detection,
      overtreatment, and a compromise in QOL due to treatment, would be very important
      issues to address for PSA screening. Although the merits of screening for
      prostate cancer would increase and the disadvantages would decrease in future,
      with the progress in diagnostic modalities and treatment strategies, it is
      crucial that PSA-based screening be conducted in accordance with well-balanced
      guidelines published by the Japanese Urological Association.

PMID- 24917002
TI  - [CONs].
AB  - In 2012, USA Preventive Services Task Force revised the guidelines for prostate
      cancer screening and recommended against prostate specific antigen(PSA)-based
      screening for prostate cancer for all age groups. This revision had a great
      impact worldwide. Immediately after the announcement, many expert societies
      expressed disagreement with this revision, but some of these have gradually come
      to accept it. When multiple organizations develop guidelines for a particular
      topic, the recommendations may differ. In this regard, the "standards for
      developing trustworthy clinical practice guidelines" presented in the report by
      the Institute of Medicine, will be helpful. The number of cases and the incidence
      rates of prostate cancer have been rapidly increasing in Japan, especially in the
      elderly population. Accordingly, sufficient information needs to be provided for
      appropriate decision-making, considering the balance between the risks and
      benefits, if cancer screening in the elderly population is to be implemented.

PMID- 24917003
TI  - [A phase II pharmacological study of leuprolide acetate 6-month depot, TAP-144-SR
      (6M), in treatment-Nazve patients with prostatic cancer who received a single
      subcutaneous or intramuscular injection].
AB  - The aim of this phase II study was to evaluate the pharmacokinetics,
      pharmacodynamics, efficacy, and safety of a 6- month depot formulation of a
      luteinizing hormone-releasing hormone (LH-RH) agonist, TAP-144-SR (6M), in
      Japanese treatment-naIve patients with prostatic cancer. Each subject received a
      single subcutaneous or intramuscular injection of TAP- 144-SR (6M) and was
      monitored for 24 weeks. The primary endpoint was the change in serum testosterone
      levels. The serum testosterone level in six subjects who received 22.5 mg of TAP
      144 (SR) subcutaneously decreased below the castrate level after 4 weeks and
      remained suppressed during the 24 weeks of follow-up. With regard to safety, TAP
      144-SR (6M)was not associated with any additional concerns compared to those
      reported for the approved 1-month and 3-month depot formulations of TAP-144-SR.
      In addition, 30 mg of TAP-144-SR (6M) was administered subcutaneously to six
      subjects, and, on the basis of the results, the optimal clinical dosage of TAP
      144-SR (6M) in Japan was considered to be 22.5 mg. Outcomes with 22.5mg TAP-144
      SR (6M) administered intramuscularly were similar to those with TAP-144-SR (6M)
      administered subcutaneously.

PMID- 24917004
TI  - [Estimation of peritoneal dissemination in patients with unresectable advanced or
      recurrent colorectal cancer who underwent curative resection after combination
      chemotherapy].
AB  - In a group of 209 colorectal cancer patients with unresectable tumors, 10
      patients underwent curative resection after combination chemotherapy at our
      hospital between 2006 and 2012. Of these 10 patients, 5 presented with peritoneal
      dissemination at the start of chemotherapy. With the exception of 1 patient with
      peritoneal recurrence, peritoneal dissemination and liver metastasis were
      observed in all patients at the time of diagnosis of colorectal cancer. Computed
      tomography (CT) and/ or positron emission tomography-CT examination revealed
      disappearance of peritoneal dissemination in response to chemotherapy, except in
      1 patient with peritoneal recurrence. After combination chemotherapy, surgical
      resection of liver metastases and peritoneal dissemination was performed.
      Pathological and intraoperative findings indicated disappearance of peritoneal
      dissemination in 3 patients and P2 grade peritoneal dissemination in 1 patient.
      In the patient with peritoneal recurrence, 1 tumor was completely resected.
      Interestingly, none of the 3 patients that exhibited complete disappearance of
      peritoneal dissemination showed peritoneal recurrence, although 1 patient
      exhibited metastases in the lung and non-regional lymph nodes. In contrast, the
      patient with P2 grade peritoneal dissemination showed peritoneal recurrence and
      lung metastasis. All 5 patients survived (duration from diagnosis of colorectal
      cancer, 31-83 months). Herein, we report the use of combination chemotherapy to
      achieve the disappearance of peritoneal dissemination, changing unresectable
      colorectal cancer with peritoneal dissemination into resectable cancer.

PMID- 24917005
TI  - [Risk factors for cardiotoxicity during fluorouracil and cisplatin combination
      chemotherapy].
AB  - We investigated the incidence of cardiovascular symptoms in patients treated with
      fluorouracil and cisplatin (FP) combination chemotherapy. Between April 2010 and
      March 2011, 61 patients were treated with FP therapy at the Department of
      Gastroenterology, Niigata Prefectural Cancer Center Hospital. Within 1 week of
      treatment and within the first or second course of therapy, six patients
      developed chest pain. To investigate the risk factors for cardiotoxicity
      following FP therapy, patients were divided into cardiotoxicity incidence and non
      incidence groups. The prevalence of diabetes, hypertension, and heart disease was
      not significantly different between the two groups. Furthermore, serum sodium and
      potassium levels were not altered following FP therapy. Therefore, no definitive
      risk factors for cardiotoxicity were identified. These results suggest that while
      FP chemotherapy-induced nausea, vomiting, and renal damage are serious adverse
      effects, further attention should also be paid to the potential cardiotoxic
      effects of FP therapy.

PMID- 24917006
TI  - [Awareness about medical expenses and certifications of eligibility for limited
      health insurance payments for chemotherapy among clinicians at the Ehime Cancer
      Care Network Priority Hospitals (Ehime Cancer Kyoten Hospitals)].
AB  - The "Cancer Chemotherapy and its Management" subcommittee at the Ehime Cancer
      Care Network Priority Hospitals (Ehime Cancer Kyoten Hospitals)with a focus on
      medical expenses associated with chemotherapy, surveyed awareness among 98
      clinicians regarding certifications of eligibility for Limited Health Insurance
      Payments during cancer treatment. This committee also lists social and clinical
      problems encountered at the Ehime Cancer Care Network Priority Hospitals. In our
      survey, 78% of clinicians were consulted about medical expenses associated with
      chemotherapy and were actively involved in resolving medical expense problems and
      resulting correspondences. However, only 38% of clinicians could explain the
      details of the Japanese guideline on the catastrophic cap and the certifications
      of eligibility for Limited Health Insurance Payments. This knowledge deficit was
      more pronounced in younger residents. From our analyses of the awareness about
      medical expenses among clinicians, we recommend the establishment of the
      following systems for the management of cancer patients. First, establish a
      reporting system and early consultation on the catastrophic cap and the
      certifications of eligibility before initiating cancer treatment. Second,
      education regarding medical expenses should be mandatory for clinicians,
      especially for young residents. Third, patients with cancer suffering in the
      interval of the medical expense and the social system should be relieved with new
      systems.

PMID- 24917007
TI  - [Verification of reduction in preparation time and cost of cyclophosphamide when
      using the closed-system drug transfer device].
AB  - The closed-system transfer device (CSTD), which is used to prevent the exposure
      of medical staff to anticancer drugs, has been reported to allow safe preparation
      and administration of these drugs to patients. At many medical institutions,
      however, the use of such devices is limited to select anticancer drugs. This
      could be attributable to the longer preparation time compared to the conventional
      injection technique with a syringe and needle, as well as the fact that the
      anticancer drugs are too expensive to be covered by the remuneration available
      for medical services. Against this background, we measured the time required to
      prepare cyclophosphamide(CPA)and estimated the cost incurred. Our results
      indicated that the preparation time for either a single dose of 100 mg CPA or a
      combination of 100 mg CPA and 500 mg of another drug(100mg+500 mg group)was
      significantly longer than that for 500 mg of a single drug. On the other hand,
      use of a CSTD reduced the total cost (drug cost+CSTD cost)on switching to a
      single dose of 500 mg, resulting in a 5-year savings as follows: 3,755,217 yen
      for ChemoCLAVE(r), 6,302,622 yen for PhaSeal(r), and 2,698,451 yen for
      Chemosafe(r). These findings suggest that the appropriate selection of drugs,
      including a large standard dose of CPA, allows shortened preparation time and
      reduced total drug cost as well as CSTD cost.

PMID- 24917008
TI  - [Comparison of the chemoimmunotherapeutic effect of doxorubicin and bafilomycin
      A1 in mouse neuroblastoma cells].
AB  - The aim of this study was to compare the ability of the drugs doxorubicin and
      Bafilomycin-A1(Baf-A1)to promote an immune reaction following the induction of
      cell death in a mouse neuroblastoma model. Neuro-2a cells were cultured in medium
      containing doxorubicin or Baf-A1. Bone marrow-derived dendritic cells(BM-DCs)were
      co-cultured with neuro-2A cells that were grown in doxorubicin- or Baf-A1
      containing media, and phagocytosis of neuro-2a cells by the BN-DCs was evaluated.
      Additionally, dead neuro-2a cells were co-cultured with CD8a + lymphocytes and BM
      DCs, and the proliferation of CD8a + cells was evaluated. Interferon-g(IFN
      g)production was used as an indexof the immune response. Dead neuro-2a cells
      treated with doxorubicin were phagocytosed effectively compared to the cells
      treated with Baf-A1. However, phagocytosis of cells treated with Baf-A1 was
      promoted after stimulation with CpG oligodeoxynucleotide (CpG-ODN). When CD8a +
      cells were co-cultured with BM-DCs and doxorubicin-treated neuro-2a cells, CD8a +
      lymphocyte proliferation was observed. There was no statistical difference in IFN
      g secretion between the doxorubicin-treated and Baf-A1-treated cells. However,
      after stimulation by CpG-ODN, IFN-g production was more effectively observed in
      the Baf-A1-treated cells. Induction of cell death by doxorubicin or Baf-A1 could
      possibly enhance antitumor immunity in patients receiving chemotherapy for
      neuroblastoma. Selection of anti-tumor agents and stimulation of BM-DCs with a
      toll-like receptor (TLR) agonist is considered important in promoting antitumor
      activity after chemotherapy.

PMID- 24917009
TI  - [Clinical experience of the use of pemetrexed (PEM) combined with cisplatin
      (CDDP)/Carboplatin (CBDCA) followed by long-term maintenance PEM in patients with
      non-squamous non-small cell lung cancer].
AB  - This study evaluated the efficacy and safety of pemetrexed and carboplatin
      (CBDCA) or cisplatin (CDDP) followed by maintenance pemetrexed for cases of
      advanced non-squamous non-small cell lung cancer (NSCLC) that were treated in our
      hospital. Patients received pemetrexed (PEM 500mg/m2) and CBDCA(area under the
      curve, 5 mg/[mL/min]) or CDDP (75 mg/m2) every 21 days. For patients without
      disease progression after 4-6 courses, pemetrexed was continued until disease
      progression or unacceptable toxicity. Fourteen patients received maintenance
      pemetrexed(median, 11.5 courses; range, 4- 43 courses). Among the 14 patients,
      the median progression-free survival time from the beginning of the induction
      treatment was 13 months. Continuation maintenance with pemetrexed after cisplatin
      plus pemetrexed induction is recommended as a first-line treatment for patients
      who have advanced non-squamous NSCLC and as a maintenance strategy.

PMID- 24917010
TI  - [A case of primary unknown cancer difficult to distinguish from lung cancer].
AB  - A 26-year-old man was admitted to our hospital with dyspnea, fever, and weight
      loss. A chest X-ray showed multiple tumor shadows, and a computed tomography (CT)
      scan showed swelling of the mediastinal and hilar lymph nodes, a mass in the
      retroperitoneum, and an embolus in the inferior vena cava. A biopsy from the left
      cervical lymph node revealeda poorly differentiated adenocarcinoma. Metastatic
      lung cancer was suspected, but in spite of the examinations, its primary site was
      unknown. Serum alfa-fetoprotein(AFP)was slightly elevated, but an AFP stain of
      the tumor was negative. The patient's respiratory failure rapidly worsened, and
      therefore, additional examinations could not be performed. The patient received
      chemotherapy with carboplatin and paclitaxel. His condition improved, but the
      tumor increased in size after 5 courses of chemotherapy. He received chemotherapy
      with docetaxel as second-line treatment, but it was not effective. The third-line
      chemotherapy regimen with carboplatin and gemcitabine was effective. In total, he
      received 7 lines of chemotherapy, and he lived for approximately 12 months since
      receiving the first chemotherapy regimen. After he died, we were able to perform
      OCT-4 immunohistochemistry on a tumor biopsy specimen from the lymph node, which
      came back positive for OCT-4. Therefore, we made a final diagnosis of
      extragonadal germ cell cancer syndrome.

PMID- 24917011
TI  - [A case of breast cancer treated with chemotherapy after resection of giant
      ovarian metastasis].
AB  - A 49-year-old female patient presented with lower abdominal pain and
      constipation. Computed tomography revealed left breast cancer with lymph node
      metastases, a peritoneal metastasis, bilateral hydronephrosis, and ovarian
      metastasis. The giant ovarian metastasis occupied the pelvic cavity and was
      responsible for her symptoms of digestive obstruction. Both ovaries were resected
      as a palliative measure. Three cycles of weekly paclitaxel were successfully
      administered, leading to the disappearance of malignant ascites. Hence, reduction
      surgery for ovarian metastasis in the treatment of breast cancer increased the
      effectiveness of the chemotherapy by improving the patient's general condition. 

PMID- 24917012
TI  - Locally advanced breast cancer with bleeding - two cases effectively treated with
      bevacizumab plus weekly paclitaxel.
AB  - Bleeding is one of the serious adverse events of bevacizumab (BV). In our report,
      two patients had locally advanced breast cancer with bleeding. They received BV
      plus weekly paclitaxel (PTX), and good local control was observed. Case 1: The
      patient was a 50-year-old postmenopausal woman. She had left-sided breast cancer
      (T4cN2cM1 [bone]-stageIV) that was negative for estrogen receptor (ER), negative
      for progesterone receptor(PgR), and 1+for human epidermal growth factor receptor
      2 (HER2). The patient began receiving different regimens of chemotherapy: 5
      fluorouracil (5-FU), epirubicin (EPI), and cyclophosphamide(CPA), (FEC); PTX;
      docetaxel (DTX); and gemcitabine (GEM) plus PTX. Subsequently, she received BV
      plus PTX. The tumor was markedly reduced in size at the completion of 2 cycles.
      Bleeding and exudate were also reduced. The patient had a partial response until
      the sixth cycle, and good local control was obtained. However, the patient had
      progressive disease at the completion of 8 cycles. Therefore, therapy was changed
      to capecitabine(CAP)plus CPA, but the patient died one year after she began
      treatment with BV plus PTX. Case 2: The patient was a 76-year-old postmenopausal
      woman. She had right-sided breast cancer (T4bN3bM1[lung]-stageIV) that was
      negative for ER, negative for PgR, and 0 for HER2. The patient began receiving
      different regimens of chemotherapy: EPI and CPA (EC); and PTX. Subsequently, she
      received BV plus PTX. The tumor was markedly reduced in size at the completion of
      2 cycles. Bleeding and exudate were also reduced. The patient had a partial
      response until the third cycle, and good local control was obtained. However, the
      patient had progressive disease at the completion of 4 cycles. Therefore, therapy
      was changed to CAP and DTX, but the patient died six months after she began
      treatment with BV plus PTX.

PMID- 24917013
TI  - [A case of advanced gastric cancer with para-aortic lymph node metastases
      responding to S-1/CDDP chemotherapy that leads to a pathological complete
      response].
AB  - A 66-year-old man complaining of epigastralgia was referred to our hospital. We
      examined the patient and diagnosed advanced gastric cancer (ML, type 3, por, cT3,
      cN3, cH0, cP0, cM1[LYM], cStage IV). A poor outcome was predicted, so we
      attempted induction chemotherapy and expected tumor downstaging. We chose S
      1/CDDP therapy. S-1 was administered orally for 21 days, followed by CDDP div on
      day 8. Total gastrectomy and lymph node dissection (D2+No. 12a, No. 13,16) was
      performed using Roux-en-Y reconstruction. Histological examination of the
      resected stomach and lymph nodes revealed no residual cancer cells, suggesting
      complete histological remission (grade 3) according to the Japanese
      classification of gastric carcinoma. The patient has been in good health without
      recurrence for 12 months after surgery.

PMID- 24917014
TI  - [Report of a gastric adenocarcinoma patient who developed multiple skin
      metastasis after gastrectomy].
AB  - A 59-year-old man with gastric cancer underwent a total gastrectomy with
      splenectomy and D2 lymph node dissection. Pathological findings after the first
      operation were as follows: ML, AntLess, type 3, por, pT3, ly1, v0, and M, Post, 0
      II c, tub1, pT1b2, ly0, v0, pN2M0P0H0, pStage IIIA. At 3 years and 6 months after
      the operation, multiple small nodules were noted on the skin of his face, neck,
      body, and arms. Biopsy of a skin lesion indicated that it was a metastatic skin
      cancer resulting from an adenocarcinoma. Thus, we diagnosed the lesions as skin
      metastases originating from an adenocarcinoma of the stomach. We also detected
      the presence of multiple metastases to the bone and lymph nodes, and we have
      treated the patient with chemotherapy. Metastases to the umbilicus from gastric
      cancer are termed as Sister Mary Joseph's nodules (SMJN). Although cases of SMJN
      are often reported, cases of multiple metastases from gastric cancer, without
      invasion to the umbilicus, are rare.

PMID- 24917015
TI  - [A case of S-1/CDDP-resistant recurrent gastric cancer responsive to
      capecitabine/CDDP].
AB  - We present a case of recurrent gastric cancer in which stable disease status was
      achieved for four months due to treatment with capecitabine/cisplatin (CDDP)after
      the failure of multiple anticancer drugs including S-1/CDDP. A 67-year-old man
      was diagnosed with multiple liver metastases one year after distal gastrectomy+D2
      dissection for gastric cancer. S-1/CDDP was given as the first-line treatment,
      followed by paclitaxel (PTX), irinotecan (CPT-11), and docetaxel (DOC). The tumor
      in the anterior segment of the liver was resistant to all of these chemotherapies
      except for PTX, which is why the regimens were changed. However, this tumor
      shrank and achieved stable disease status for four months after capecitabine/CDDP
      therapy given as fifth-line treatment. Our case suggests that S-1 and
      capecitabine do not always exhibit cross-resistance. Therefore, capecitabine may
      be effective in S-1-pretreated patients, and vice versa.

PMID- 24917016
TI  - [A case of advanced rectal cancer that showed complete response to the addition
      of XELOX+bevacizumab therapy to preoperative chemoradiotherapy with S-1/CPT-11].
AB  - A 51-year-old man presented with a chief complaint of constipation. Rectal cancer
      was detected up to 13 cm proximal to the anal verge. The cancer was a fully
      circumferential type II tumor that was accompanied by prostate invasion and lymph
      node metastasis. After sigmoid colostomy, preoperative chemoradiotherapy with S
      1/irinotecan (CPT-11; total 50 Gy) was administered, resulting in tumor volume
      reduction. However, because of residual invasion in some parts of the prostate,
      therapy with capecitabine and oxaliplatin (XELOX) plus bevacizumab was added to
      avoid pelvic exenteration. Because magnetic resonance imaging revealed no
      invasion prostate after 7 courses of the therapy, abdominoperineal resection of
      the rectum was performed. Pathological examination revealed no residual tumor
      cells, and a pathological complete response was thus confirmed. The addition of
      chemotherapy to preoperative chemoradiotherapy was considered to be an effective
      strategy for locally advanced rectal cancer in this case.

PMID- 24917017
TI  - [A case of pathological complete response of advanced rectal cancer with liver
      metastasis accompanied by tumor thrombus following treatment with
      bevacizumab/FOLFOX4 chemotherapy].
AB  - A 58-year-old man underwent low anterior resection for type 2 rectal cancer with
      liver metastasis. An abdominal computed tomography (CT) scan showed multiple
      hepatic tumors (in S2, S3, S4, and S6) and a filling defect in the left portal
      vein. Pathological examination revealed a moderately differentiated
      adenocarcinoma, pSS, pN0, ly0, v3, with a tumor thrombus in the portal vein.
      After surgery, the patient was treated with combined chemotherapy of
      bevacizumab/Leucovorin and fluorouracil with oxaliplatin (FOLFOX4). After 11
      courses of chemotherapy, tumor marker levels normalized, and the sizes of the
      liver metastases and thrombus in the left portal vein remarkably decreased.
      Resection of the left hepatic lobe and a partial resection of S6 were performed.
      Pathological examination revealed no residual cancer cells and indicated that the
      histological classification due to the chemotherapy regimen was Grade 3. The
      patient was alive for 5 years after the initial surgery, without recurrence.

PMID- 24917018
TI  - [Effective chemotherapy with bevacizumab/FOLFOX4 for neuroendocrine carcinoma of
      the ascending colon - a case study].
AB  - A 63-year-old woman underwent surgery for Stage IV cancer of the ascending colon
      with multiple lymph node metastases. The pathological diagnosis was
      neuroendocrine carcinoma. Following first-line chemotherapy, the patient
      presented clinically with progressive disease (PD). Second-line chemotherapy with
      bevacizumab/Leucovorin and 5-fluorouracil with oxaliplatin (FOLFOX4) was
      effective and a partial response (PR) was achieved after 7 courses of therapy, as
      determined by computed tomography (CT) examination. Neuroendocrine carcinoma is
      known to be extremely malignant; however, this case suggests that chemotherapy
      with bevacizumab may improve the prognosis of this disease.

PMID- 24917020
TI  - [Radical resection of a locally advanced pancreatic tail adenosquamous carcinoma
      treated with S-1 and gemcitabine as neoadjuvant chemotherapy - a case report].
AB  - We report a case of locally advanced pancreatic tail adenosquamous carcinoma that
      was treated by performing R0 resection after neoadjuvant chemotherapy with S-1
      and gemcitabine. A 75-year-old man visited our hospital because of left lateral
      abdominal pain. On the basis of computed tomography and endoscopic biopsy
      findings, an 80-mm locally advanced pancreatic tail carcinoma with direct
      invasion to the gastric upper body, splenic flexure of the colon, and left kidney
      was diagnosed. Combined chemotherapy with S-1 and gemcitabine was initiated for
      reduction in the tumor size. After 11 courses of treatment, computed tomography
      revealed a partial response in tumor size reduction. Grade 3 neutropenia was
      observed as an adverse event. Distal pancreatectomy, proximal gastrectomy,
      partial resection of the descending colon, resection of the left kidney and left
      adrenal gland, and D2 lymph node dissection were performed. The pathological
      diagnosis was adenosquamous carcinoma in the pancreatic tail, and an R0 resection
      was achieved. However, a month after surgery, multiple distant liver metastases
      were observed. Neoadjuvant chemotherapy with S-1 and gemcitabine may reduce the
      tumor size in locally advanced pancreatic tail adenosquamous carcinoma and
      increase the R0 resection rate. However, treatment for distant metastasis is
      warranted in cases of pancreatic adenosquamous carcinoma. 

PMID- 24917019
TI  - [A case of effective treatment with S-1/gemcitabine chemotherapy and resection
      for advanced pancreatic cancer with peritoneal dissemination].
AB  - A 69-year-old man was admitted to our hospital for abdominal pain. An abdominal
      computed tomography(CT)scan revealed pancreatictail cancer with peritoneal
      dissemination. We administered systemic chemotherapy consisting of S-1 and
      gemcitabine. After 10 courses, the peritoneal dissemination had disappeared and
      tumor marker levels returned to almost normal values. Thus, we considered the
      patient to have an effective response, so we performed a distalpancreatectomy and
      partial resection of the stomach, transverse colon, and left adrenal gland.
      Eleven months after the operation, the patient is alive with no recurrence.

PMID- 24917021
TI  - [Retrospective analysis of Charlson comorbidity index (CCI)].
AB  - Owing to the advance of supportive care and the development of molecular targeted
      therapies, the elderlies or patients who have comorbidities have been treated
      more than before. The assessment of the comorbidity is indispensable to select
      the appropriate treatment or the control of following therapy. Some indices to
      determine them have been developed in western countries but not in Japan. The
      index which is used most is the Charlson comorbidity index (CCI). This index has
      never been evaluated in Japan. So we investigated the utility of the index for
      Japanese population. We surveyed retrospectively 498 patients aged 65 or more
      patients with colon cancer, breast cancer, lung cancer that have been treated in
      our hospital during 2002-2007. According to CCI, patients are classified into
      three groups and verified 1-year and 3-year survival rate. 1-year survival rate
      was 76.9% in groups of 0 points, 83.5% in groups of1 -5 points, 75.0% in the
      group of six or more points respectively (p=0.19). 3-year survival rate were
      59.0%, 63.1%, 75.0%, respectively (p=0.46). Multivariate analysis identified age
      (>= 50), Sex (man), stage (III and IV) as significant predictors for worse OS at
      3-year. However, there was no significant difference in CCI. There are some items
      which frequency is zero, so the items of CCI may not match to Japanese
      population. Presence of existing disease is an important factor for the cancer
      therapy, and it should be evaluated accurately. It is urgently necessary to
      develop an evaluation method and establish the scale.

PMID- 24917022
TI  - Twitch potentiation induced by two different modalities of neuromuscular
      electrical stimulation: implications for motor unit recruitment.
AB  - INTRODUCTION: We tested the hypothesis that twitch potentiation would be greater
      following conventional (CONV) neuromuscular electrical stimulation (50-us pulse
      width and 25-Hz frequency) compared with wide-pulse high-frequency (WPHF)
      neuromuscular electrical stimulation (1-ms, 100-Hz) and voluntary (VOL)
      contractions, because of specificities in motor unit recruitment (random in CONV
      vs. random and orderly in WPHF vs. orderly in VOL). METHODS: A single twitch was
      evoked by means of tibial nerve stimulation before and 2 s after CONV, WPHF, and
      VOL conditioning contractions of the plantar flexors (intensity: 10% maximal
      voluntary contraction; duration: 10 s) in 13 young healthy subjects. RESULTS:
      Peak twitch increased (P<0.05) after CONV (+4.5+/-4.0%) and WPHF (+3.3+/-5.9%),
      with no difference between the 2 modalities, whereas no changes were observed
      after VOL (+0.8+/-2.6%). CONCLUSIONS: Our results demonstrate that presumed
      differences in motor unit recruitment between WPHF and CONV do not seem to
      influence twitch potentiation results.

PMID- 24917023
TI  - Serum IL-18 as a potential specific marker for differentiating systemic juvenile
      idiopathic arthritis from incomplete Kawasaki disease.
AB  - Clinical features and laboratory parameters in patients with incomplete Kawasaki
      disease (KD) and systemic juvenile idiopathic arthritis (s-JIA) tend to overlap.
      Furthermore, there have been no definite biomarkers for these diseases. This
      situation makes the clinical diagnosis of these patients difficult. In this
      study, we aimed to measure serum interleukin (IL)-18 and IL-6 levels in patients
      with s-JIA who were initially diagnosed with incomplete KD and compare these data
      with those in patients with complete KD and arthritis. Serum IL-18 levels in
      patients with s-JIA were significantly elevated compared with those in patients
      with KD and arthritis. Pediatricians should be aware that the presentation of s
      JIA can mimic incomplete KD. Because the clinical features overlap, a high index
      of suspicion is warranted. The measurement of serum IL-18 may be useful for
      differentiating s-JIA from KD.

PMID- 24917024
TI  - A case of cutaneous sarcoid vasculitis with livedo and review of the literature.

PMID- 24917025
TI  - Highly efficient folding of multi-disulfide proteins in superoxidizing
      Escherichia coli cytoplasm.
AB  - In this study, we monitored the thiol-disulfide redox potential of different
      Escherichia coli strains using redox-sensitive variants of green fluorescent
      protein. The cells with extreme oxidizing cytoplasm were generated by introducing
      a highly efficient disulfide relay system. The developed cells have exceptionally
      efficient de novo disulfide bond formation and significantly improve the
      oxidative folding of the client multi-disulfide proteins. Superoxidizing E. coli
      strain provides an effective method for the high-level production of recombinant
      disulfide-containing proteins.

PMID- 24917026
TI  - Spinal neuronal correlates of tapentadol analgesia in cancer pain: a back
      translational approach.
AB  - BACKGROUND: Pain is a common and highly debilitating complication for cancer
      patients significantly compromising their quality of life. Cancer-induced bone
      pain involves a complex interplay of multiple mechanisms including both
      inflammatory and neuropathic processes and also some unique changes. Strong
      opioids are a mainstay of treatments but side effects are problematic and can
      compromise optimal pain control. Tapentadol is a novel dual-action drug, both
      stimulating inhibitory MU-opioid receptors (MOR) and mediating noradrenaline
      reuptake inhibition (NRI) leading to activation of the inhibitory alpha-2
      adrenoceptor. It has been demonstrated to treat effectively both acute and
      chronic pain. We here demonstrate the efficacy in a model of cancer-induced bone
      pain. METHODS: MRMT-1 mammary carcinoma cells were inoculated into the tibia of 6
      week-old rats and 2 weeks after, the neuronal responses to a wide range of
      peripheral stimulation were evaluated. The recordings were made from wide-dynamic
      range neurons in lamina V of the dorsal horn before and after administration of
      tapentadol as well as antagonists of the two mechanisms, naloxone or atipamezole.
      RESULTS: We found marked inhibitions of the neuronal activity with efficacy
      against mechanical, thermal and electrically evoked activity following tapentadol
      administration. In addition, the effects of the drug were fully reversible by
      naloxone and partly by atipamezole, supporting the idea of MOR-NRI dual actions.
      CONCLUSIONS: These findings add to the mechanistic understanding of cancer
      induced bone pain and support the sparse clinical data indicating a possible use
      of the drug as a therapeutic alternative for cancer patients with metastatic pain
      complication.

PMID- 24917027
TI  - Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine
      complexes for myocardial infarction.
AB  - Inflammatory response in myocardial ischemia-reperfusion injury plays a critical
      role in ventricular remodeling. To avoid deleterious effects of overwhelming
      inflammation, we blocked the expression of receptor for advanced glycation end
      products (RAGE), a key mediator of the local and systemic inflammatory responses,
      via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low
      molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier
      to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via
      electrostatic and hydrophobic interactions. The siRAGE/DA-PEI formulation having
      negligible toxicity could enhance intracellular delivery efficiency and
      successfully suppress RAGE expression both in vitro and in vivo. Furthermore, the
      cardiac administration of siRAGE/DA-PEI reduced apoptosis and inflammatory
      cytokine release, subsequently led to attenuation of left ventricular remodeling
      in rat myocardial infarction model. The potential therapeutic effects of RAGE
      gene silencing on myocardial ischemia-reperfusion injury may suggest that the
      siRAGE/DA-PEI delivery system can be considered as a promising strategy for
      treating myocardial infarction. 

PMID- 24917029
TI  - The degeneration of biological cardiovascular prostheses under pro-calcific
      metabolic conditions in a small animal model.
AB  - In order to allow for a comparative evaluation of the in vivo degeneration of
      biological and tissue-engineered heart valves and vascular grafts, a small animal
      model of accelerated cardiovascular calcification is desired. Wistar rats (n =
      102; 6 groups) were fed ad libitum with regular chow and 5 different regimens of
      pro-calcific diet supplemented with combinations of vitamin D (VD), cholesterol
      (CH) and dicalcium phosphate (PH). Moreover, cryopreserved (n = 7) or detergent
      decellularized rat aortic conduit grafts (n = 6) were infrarenally implanted in
      Wistar rats under severely pro-calcific conditions. The follow-up lasted up to 12
      weeks. High-dose application of VD (300,000 IU/kg), CH (2%) and PH (1.5%)
      resulted in elevated serum calcium and cholesterol levels as well as LDL/HDL
      ratio. It increased the tissue MMP activity visualized by in situ zymography and
      caused significantly aggravated calcification of the native aortic valve as well
      as the aortic wall as assessed by histology and micro-computed tomography.
      (Immuno)histology and quantitative real-time PCR revealed chondro-osteogenic cell
      transformation, lipid deposition, nitrosative stress and low-level inflammation
      to be involved in the formation of calcific lesions. Despite pro-calcific in vivo
      conditions, decellularization significantly reduced calcification, inflammation
      and intimal hyperplasia in aortic conduit implants. A well balanced dietary
      trigger for pathologic metabolic conditions may represent an appropriate mid-term
      treatment to induce calcifying degeneration of aortic valves as well as vascular
      structures in the systemic circulation in rats. With respect to experimental
      investigation focusing on calcifying degeneration of native or prosthetic tissue,
      this regimen may serve as a valuable tool with a rapid onset and multi-facetted
      character of cardiovascular degeneration. 

PMID- 24917028
TI  - Naturally enveloped AAV vectors for shielding neutralizing antibodies and robust
      gene delivery in vivo.
AB  - Recently adeno-associated virus (AAV) became the first clinically approved gene
      therapy product in the western world. To develop AAV for future clinical
      application in a widespread patient base, particularly in therapies which require
      intravenous (i.v.) administration of vector, the virus must be able to evade pre
      existing antibodies to the wild type virus. Here we demonstrate that in mice, AAV
      vectors associated with extracellular vesicles (EVs) can evade human anti-AAV
      neutralizing antibodies. We observed different antibody evasion and gene transfer
      abilities with populations of EVs isolated by different centrifugal forces. EV
      associated AAV vector (ev-AAV) was up to 136-fold more resistant over a range of
      neutralizing antibody concentrations relative to standard AAV vector in vitro.
      Importantly in mice, at a concentration of passively transferred human antibodies
      which decreased i.v. administered standard AAV transduction of brain by 80%,
      transduction of ev-AAV transduction was not reduced and was 4000-fold higher.
      Finally, we show that expressing a brain targeting peptide on the EV surface
      allowed significant enhancement of transduction compared to untargeted ev-AAV.
      Using ev-AAV represents an effective, clinically relevant approach to evade human
      neutralizing anti-AAV antibodies after systemic administration of vector. 

PMID- 24917030
TI  - A microchip filter device incorporating slit arrays and 3-D flow for detection of
      circulating tumor cells using CAV1-EpCAM conjugated microbeads.
AB  - Circulating tumor cells (CTCs) are rare cells and the presence of these cells may
      indicate a poor prognosis and a high potential for metastasis. Despite highly
      promising clinical applications, CTCs have not been investigated thoroughly, due
      to many technical limitations faced in their isolation and identification.
      Current CTC detection techniques mostly take the epithelial marker epithelial
      cell adhesion molecule (EpCAM), however, accumulating evidence suggests that CTCs
      show heterogeneous EpCAM expression due to the epithelial-to-mesenchymal
      transition (EMT). In this study, we report that a microchip filter device
      incorporating slit arrays and 3-dimensional flow that can separate heterogeneous
      population of cells with marker for CTCs. To select target we cultured breast
      cancer cells under prolonged mammosphere culture conditions which induced EMT
      phenotype. Under these conditions, cells show upregulation of caveolin1 (CAV1)
      but down-regulation of EpCAM expression. The proposed device which contains CAV1
      EpCAM conjugated bead has several tens of times increased throughput. More
      importantly, this platform enables the enhanced capture yield from metastatic
      breast cancer patients and obtained cells that expressed various EMT markers.
      Further understanding of these EMT-related phenotypes will lead to improved
      detection techniques and may provide an opportunity to develop therapeutic
      strategies for effective treatment and prevention of cancer metastasis. 

PMID- 24917032
TI  - The psychological impact of providing women with risk information for pre
      eclampsia: a qualitative study.
AB  - OBJECTIVE: a new first-trimester universal antenatal screening test for pre
      eclampsia was introduced into two UK hospitals. The aim of this study was to
      investigate the potential psychological benefits, harms and acceptability of
      providing pregnant women with formal risk information for pre-eclampsia. DESIGN:
      cross-sectional interview study. Women were interviewed using a theoretically
      informed semi-structured schedule and transcripts were analysed thematically
      using Framework Analysis. SETTING AND PARTICIPANTS: primigravid women receiving
      antenatal care at a central London National Health Service Foundation Trust found
      either high-risk or low-risk for pre-eclampsia. FINDINGS: 15 primigravid women
      who received high risk (n=10) or low risk (n=5) results of a 12-week pre
      eclampsia screening test were interviewed. Two types of coping typologies were
      evident from the data. The first were 'danger managers' who had an internal sense
      of control, were focused on the risk that pre-eclampsia presented to them and
      exhibited information seeking, positive behaviour changes, and cognitive
      reappraisal coping mechanisms. The second were 'fear managers' who had an
      external sense of control, were focused on the risk that pre-eclampsia presented
      to the fetus, and exhibited avoidance coping mechanisms. In addition to these
      typologies, three universal themes of 'medicalising the pregnancy', 'embracing
      technology' and 'acceptability' emerged from the data. KEY CONCLUSIONS: there are
      potential positive and negative unintended consequences following a first
      trimester screening test for pre-eclampsia. A positive consequence could be self
      instigated behaviour change, whereas a negative consequence could be reduced self
      monitoring of fetal movements as the pregnancy develops. IMPLICATIONS FOR
      PRACTICE: this study indicates that women with an increased risk of pre-eclampsia
      would be willing to engage in efforts to reduce their risk of pre-eclampsia, and
      there is a potential to use this screening test as a basis for improving health
      more broadly.

PMID- 24917031
TI  - The use of bi-layer silk fibroin scaffolds and small intestinal submucosa
      matrices to support bladder tissue regeneration in a rat model of spinal cord
      injury.
AB  - Adverse side-effects associated with enterocystoplasty for neurogenic bladder
      reconstruction have spawned the need for the development of alternative graft
      substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa
      (SIS) matrices were investigated for their ability to support bladder tissue
      regeneration and function in a rat model of spinal cord injury (SCI). Bladder
      augmentation was performed with each scaffold configuration in SCI animals for 10
      wk of implantation and compared to non-augmented control groups (normal and SCI
      alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18)
      while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective
      survival rates of 83% (10/12) and 75% (9/12) over the course of the study period.
      Histological (Masson's trichrome analysis) and immunohistochemical (IHC)
      evaluations demonstrated both implant groups supported de novo formation of
      smooth muscle layers with contractile protein expression [alpha-smooth muscle
      actin (alpha-SMA) and SM22alpha] as well as maturation of multi-layer urothelia
      expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis
      revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of
      the level of alpha-SMA+ smooth muscle bundles present in SCI-alone controls,
      while similar degrees of CK+ urothelium across all experimental groups were
      detected. Parallel evaluations showed similar degrees of vascular area and
      synaptophysin+ boutons in all regenerated tissues compared to SCI-alone controls.
      In addition, improvements in certain urodynamic parameters in SCI animals, such
      as decreased peak intravesical pressure, following implantation with both matrix
      configurations were also observed. The data presented in this study detail the
      ability of acellular SIS and bi-layer SF scaffolds to support formation of
      innervated, vascularized smooth muscle and urothelial tissues in a neurogenic
      bladder model. 

PMID- 24917034
TI  - Substituent parameters impacting isomer composition and optical properties of
      dihydroindolizine molecular switches.
AB  - In an attempt to understand which factors influence constitutional isomer control
      of 6'- and 8'-substituted dihydroindolizines (DHIs), a series of asymmetric
      pyridines was condensed with dimethyl spiro[cycloprop[2]ene-1,9'-fluorene]-2,3
      dicarboxylate. The substituents on the pyridial derivatives ranged from donating
      to withdrawing and demonstrated control over the isomeric ratios for all DHIs.
      Substituent control proved to be selective for the highly donating amino, which
      exclusively formed the 8' isomer. The same ratios were reproduced via photolytic
      experiments, which suggested that the condensation reaction is dominated by the
      product's thermodynamic stability. The electronic influences of the substituents
      extends beyond isomer control, as it impacts the DHIs' optical properties and
      electrocyclization (switching) rates to the spiro conformers. Our results allow
      us to predict the syntheses and properties of future 6'- or 8'-substituted DHIs,
      molecules that will be applied in understanding the role of the dipole vector
      orientation to work function switching. 

PMID- 24917033
TI  - Validation of the VE1 immunostain for the BRAF V600E mutation in melanoma.
AB  - BACKGROUND: BRAF mutation status, and therefore eligibility for BRAF inhibitors,
      is currently determined by sequencing methods. We assessed the validity of VE1, a
      monoclonal antibody against the BRAF V600E mutant protein, in the detection of
      mutant BRAF V600E melanomas as classified by DNA pyrosequencing. METHODS: The
      cases were 76 metastatic melanoma patients with only one known primary melanoma
      who had had BRAF codon 600 pyrosequencing of either their primary (n = 19),
      metastatic (n = 57) melanoma, or both (n = 17). All melanomas (n = 93) were
      immunostained with the BRAF VE1 antibody using a red detection system. The
      staining intensity of these specimens was scored from 0 to 3+ by a
      dermatopathologist. Scores of 0 and 1+ were considered as negative staining while
      scores of 2+ and 3+ were considered positive. RESULTS: The VE1 antibody showed a
      sensitivity of 85% and a specificity of 100% as compared to DNA pyrosequencing
      results. There was 100% concordance between VE1 immunostaining of primary and
      metastatic melanomas from the same patient. V600K, V600Q, and V600R BRAF
      melanomas did not positively stain with VE1. CONCLUSIONS: This hospital-based
      study finds high sensitivity and specificity for the BRAF VE1 immunostain in
      comparison to pyrosequencing in detection of BRAF V600E in melanomas.

PMID- 24917035
TI  - Self-reported adherence by MARS-CZ reflects LDL cholesterol goal achievement
      among statin users: validation study in the Czech Republic.
AB  - RATIONALE, AIMS AND OBJECTIVES: Measuring self-reported adherence may contribute
      to minimizing the risk of therapy failure. Hence, the main aim of the study was
      to assess the psychometric properties of the Czech version of Medication
      Adherence Report Scale (MARS-CZ) and its appropriateness for use in long-term
      statin therapy where goal levels of low-density lipoprotein cholesterol (LDL-c)
      should be achieved. METHODS: Anonymous structured interview was performed to
      determine self-reported adherence by MARS-CZ in outpatients chronically treated
      with statins. At the same time, medication records were reviewed for inclusion of
      patients into groups of those who achieved and do not achieved LDL-c goal
      according to cardiovascular risk level. Reliability and validity of MARS-CZ were
      tested as well as the relationship between adherence and LDL-c goal achievement
      was examined. RESULTS: A total of 136 (86.6%) patients completed the interview;
      mean age was 66.1 years; 49.3% were male. The mean score of MARS-CZ was 24.4 and
      showed positive skewing. Satisfactory internal consistency (Cronbach's
      alpha=0.54), strong test-retest reliability (r=0.83, P<0.001; intra-class
      correlation=0.63, 95% confidence interval: 0.35-0.81) and positive correlation
      with eight-item Morisky Medication Adherence Scale (r=0.62, P<0.001) were
      indicated. Low validity values were found between MARS-CZ and 12-item Short Form
      Health Survey mental and physical subscales. MARS-CZ score significantly
      correlated with LDL-c goal achievement (P<0.05) when all patients who achieved
      LDL-c goal (35%) reported high adherence to statin. MARS-CZ score also correlated
      with cardiovascular risk level and doctor's judgments on adjusting treatment
      targets for each patient. CONCLUSION: This study proved MARS-CZ as an acceptable
      self-reported adherence measure. In routine clinical practice, MARS-CZ could be
      helpful to reveal medication non-adherence before the alteration of drug regimen
      and thereby contributing to enhancement of statin therapy management.

PMID- 24917036
TI  - Identification and bioinformatics analysis of microRNAs associated with stress
      and immune response in serum of heat-stressed and normal Holstein cows.
AB  - MicroRNAs (miRNAs) are small single-stranded non-coding RNAs that have an
      important regulatory function in animal growth and developmental processes.
      However, the differential expression of miRNA and the role of these miRNAs in
      heat-stressed Holstein cows are still unknown. In this study, the profile of
      differentially expressed miRNAs and the target genes analysis in the serum of
      heat-stressed and normal Holstein cows were investigated by a Solexa deep
      sequencing approach and bioinformatics. The data identified 52 differentially
      expressed miRNAs in 486 known miRNAs which were changed significantly between
      heat-stressed and normal Holstein cows (fold change >2, P < 0.001). Target genes
      analysis showed that at least 7 miRNAs (miR-19a, miR-19b, miR-146a, miR-30a-5p,
      miR-345-3p, miR-199a-3p, and miR-1246) were involved in the response to stress,
      oxidative stress, development of the immune system, and immune response among the
      identified 52 differentially expressed miRNAs. Five miRNAs (miR-27b, miR-181a,
      miR-181b, miR-26a, and miR-146b) were involved in stress and immune responses and
      the expression of five miRNAs was striking (P < 0.001). In addition, RT-qPCR and
      deep-sequencing methods showed that 8 miRNAs among the 12 selected miRNAs (miR
      19a, miR-19b, miR-27b, miR-30a-5p, miR-181a, miR-181b, miR-345-3p, and miR-1246)
      were highly expressed in the serum of heat-stressed Holstein cows. GO and KEGG
      pathway analysis showed that these differentially expressed miRNAs were involved
      in a pathway that may differentially regulate the expression of stress response
      and immune response genes. Our study provides an overview of miRNAs expression
      profile and the interaction between miRNAs and their target genes, which will
      lead to further understanding of the important roles of miRNAs in heat-stressed
      Holstein cows.

PMID- 24917037
TI  - Associations of pre-pregnancy body mass index and gestational weight gain with
      pregnancy outcome and postpartum weight retention: a prospective observational
      cohort study.
AB  - BACKGROUND: Excessive gestational weight gain (GWG) is associated with pregnancy
      complications, and Norwegian Health Authorities have adopted the GWG
      recommendations of the US Institute of Medicine and National Research Council
      (IOM). The aim of this study was to evaluate if a GWG outside the IOM
      recommendation in a Norwegian population is associated with increased risk of
      pregnancy complications like hypertension, low and high birth weight,
      preeclampsia, emergency caesarean delivery, and maternal post-partum weight
      retention (PPWR) at 6 and 18 months. METHODS: This study was performed in 56 101
      pregnant women included in the prospective national Norwegian Mother and Child
      Cohort Study (MoBa) in the years 1999 to 2008. Women who delivered a singleton
      live born child during gestational week 37 to 42 were included. Maternal
      prepregnant and postpartum weight was collected from questionnaires at 17th week
      of gestation and 6 and 18 months postpartum. RESULTS: A weight gain less than the
      IOM recommendations (GWG < IOM rec.) increased the risk for giving birth to a low
      weight baby among normal weight nulliparous women. A weight gain higher than the
      IOM recommendations (GWG > IOM rec.) significantly increased the risk of
      pregnancy hypertension, a high birth weight baby, preeclampsia and emergency
      cesarean delivery in both nulliparous and parous normal weight women. Similar
      results were found for overweight women except for no increased risk for
      gestational hypertension in parous women with GWG > IOM rec. Seventy-four percent
      of the overweight nulliparous women and 66% of the obese women had a GWG > IOM
      rec. A GWG > IOM rec. resulted in increased risk of PPWR > 2 kg in all weight
      classes, but most women attained their prepregnant weight class by 18 months post
      partum. CONCLUSIONS: For prepregnant normal weight and overweight women a GWG >
      IOM rec. increased the risk for unfavorable birth outcomes in both nulliparous
      and parous women. A GWG > IOM rec. increased the risk of a PPWR > 2 kg at 18
      months in all weight classes. This large study supports the Norwegian Health
      authorities' recommendations for normal weight and overweight women to comply
      with the IOM rec.

PMID- 24917038
TI  - How wasting is saving: weight loss at altitude might result from an evolutionary
      adaptation.
AB  - At extreme altitude (>5,000 - 5,500 m), sustained hypoxia threatens human
      function and survival, and is associated with marked involuntary weight loss
      (cachexia). This seems to be a coordinated response: appetite and protein
      synthesis are suppressed, and muscle catabolism promoted. We hypothesise that,
      rather than simply being pathophysiological dysregulation, this cachexia is
      protective. Ketone bodies, synthesised during relative starvation, protect
      tissues such as the brain from reduced oxygen availability by mechanisms
      including the reduced generation of reactive oxygen species, improved
      mitochondrial efficiency and activation of the ATP-sensitive potassium (KATP )
      channel. Amino acids released from skeletal muscle also protect cells from
      hypoxia, and may interact synergistically with ketones to offer added protection.
      We thus propose that weight loss in hypoxia is an adaptive response: the amino
      acids and ketone bodies made available act not only as metabolic substrates, but
      as metabolic modulators, protecting cells from the hypoxic challenge.

PMID- 24917039
TI  - Imaging neurovascular function and functional recovery after stroke in the rat
      striatum using forepaw stimulation.
AB  - Negative functional magnetic resonance imaging (fMRI) response in the striatum
      has been observed in several studies during peripheral sensory stimulation, but
      its relationship between local field potential (LFP) remains to be elucidated. We
      performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats
      during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit
      high LFP-CBV correlation was found in the ipsilateral and contralateral sensory
      cortices (r=0.89 and 0.95, respectively), the striatal CBV responses were neither
      positively, nor negatively correlated with LFP (r=0.04), demonstrating that the
      negative striatal CBV response is not originated from net regional inhibition. To
      further identify whether this negative CBV response can serve as a marker for
      striatal functional recovery, two groups of rats (n=5 each) underwent 20- and 45
      minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was
      found in the ipsilateral striatum in both groups immediately after stroke.
      Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group
      compared with the 45-minute MCAO group (P<0.05). This study shows that fMRI
      signals could differ significantly from LFP and that the observed negative CBV
      response has potential to serve as a marker for striatal functional integrity in
      rats. 

PMID- 24917040
TI  - The vascular steal phenomenon is an incomplete contributor to negative
      cerebrovascular reactivity in patients with symptomatic intracranial stenosis.
AB  - 'Vascular steal' has been proposed as a compensatory mechanism in hemodynamically
      compromised ischemic parenchyma. Here, independent measures of cerebral blood
      flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance
      imaging (MRI) responses to a vascular stimulus in patients with ischemic
      cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients
      (n=40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted
      and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and
      CBF-weighted arterial spin labeling) functional MRI during room air and
      hypercarbic gas administration. CBF changes in regions demonstrating negative
      BOLD reactivity were recorded, as well as clinical correlates including
      symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty
      participants exhibited negative BOLD reactivity. Of these, a positive
      relationship was found between BOLD and CBF reactivity in unaffected (stenosis
      degree<50%) cortex. In negative BOLD cerebrovascular reactivity regions, three
      patients exhibited significant (P<0.01) reductions in CBF consistent with
      vascular steal; six exhibited increases in CBF; and the remaining exhibited no
      statistical change in CBF. Secondary findings were that negative BOLD reactivity
      correlated with symptomatic hemisphere by lateralizing clinical symptoms and
      prior infarcts(s). These data support the conclusion that negative hypercarbia
      induced BOLD responses, frequently assigned to vascular steal, are heterogeneous
      in origin with possible contributions from autoregulation and/or metabolism. 

PMID- 24917041
TI  - Mouse intracerebral hemorrhage models produce different degrees of initial and
      delayed damage, axonal sprouting, and recovery.
AB  - The mechanisms of delayed damage and recovery after intracerebral hemorrhage
      (ICH) remain poorly defined. Two rodent models of ICH are commonly used:
      injection of the enzyme collagenase (cICH) and injection of autologous blood
      (bICH). In mice, we compared the effects of these two models on initial and
      delayed tissue damage, motor system connections, and behavioral recovery. There
      is no difference in lesion size between models. Injection of autologous blood
      causes greater mass effect and early mortality. However, cICH produces greater
      edema, inflammation, and cell death. Injection of the enzyme collagenase causes
      greater loss of cortical connections and secondary shrinkage of the striatum.
      Intracerebral hemorrhage occurs within the motor system connections of the
      striatum. Mapping of the projections of the forelimb motor area shows a
      significant sprouting in motor cortex projections only in cICH. Both models of
      ICH produce deficits in forelimb motor control. Behavioral recovery occurs by 5
      weeks in cICH and 9 weeks in bICH. In summary, cICH and bICH differ in almost
      every facet of initial and delayed stroke pathophysiology, with cICH producing
      greater initial and secondary tissue damage and greater motor system axonal
      sprouting than bICH. Motor recovery occurs in both models, suggesting that motor
      system axonal sprouting in cICH is not causally associated with recovery. 

PMID- 24917042
TI  - Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after
      neurotoxic conditions and traumatic brain injury.
AB  - Transactivation response DNA-binding protein 43 (TDP-43) proteinopathy has
      recently been reported in chronic traumatic encephalopathy, a neurodegenerative
      condition linked to prior history of traumatic brain injury (TBI). While TDP-43
      appears to be vulnerable to proteolytic modifications under neurodegenerative
      conditions, the mechanism underlying the contribution of TDP-43 to the
      pathogenesis of TBI remains unknown. In this study, we first mapped out the
      calpain or caspase-3 TDP-43 fragmentation patterns by in vitro protease
      digestion. Concurrently, in cultured cerebrocortical neurons subjected to cell
      death challenges, we identified distinct TDP-43 breakdown products (BDPs) of 35,
      33, and 12 kDa that were indicative of dual calpain/caspase attack.
      Cerebrocortical culture incubated with calpain and caspase-fragmented TDP-43
      resulted in neuronal injury. Furthermore, increased TDP-43 BDPs as well as
      redistributed TDP-43 from the nucleus to the cytoplasm were observed in the mouse
      cortex in two TBI models: controlled cortical impact injury and overpressure
      blast-wave-induced brain injury. Finally, TDP-43 and its 35 kDa fragment levels
      were also elevated in the cerebrospinal fluid (CSF) of severe TBI patients. This
      is the first evidence that TDP-43 might be involved in acute neuroinjury and TBI
      pathology, and that TDP-43 and its fragments may have biomarker utilities in TBI
      patients. 

PMID- 24917044
TI  - Effect of chromatographic conditions and plasmid DNA size on the dynamic binding
      capacity of a monolithic support.
AB  - DNA therapies are becoming recognized alternatives for the treatment and
      prevention of severe pathologies. Although most current trials have used plasmids
      <10 kbp, in the future larger plasmids would be required. The purpose of this
      work was to study the chromatographic behavior of nongrafted carbonyldiimidazole
      monolithic disks using plasmids with different sizes under hydrophobic
      conditions. Thereunto, the purification of several plasmids was performed. Higher
      size plasmids needed lower ammonium sulfate concentration, due to the greater
      number of interactions between the plasmids and monolith. The dynamic binding
      capacity experiments for the different plasmids revealed a lower capacity for
      bigger plasmids. It was also verified that the increase of salt concentration
      from 2.5 to 3 M of ammonium sulfate increased the capacity. At the highest salt
      concentration, a slight improvement in the capacity using lower flow rate was
      observed, possibly due to compaction of plasmid molecules and its better
      organization on the monolith channels. Finally, a low pH also had a positive
      effect on the capacity. So, this monolithic support proved to be appropriate to
      purify the supercoiled isoform of different plasmids with different sizes,
      providing a valuable instrument as a purification technique.

PMID- 24917045
TI  - Hepatic metabolite profiles in mice with a suboptimal selenium status.
AB  - Selenium is an essential trace element and mediates its functions via various
      selenoproteins such as glutathione peroxidases or thioredoxin reductases. A
      suboptimal selenium supply causes metabolic disturbances and is associated with
      an increased risk to develop different disorders, including cancer or
      cardiovascular diseases. This study aimed to assess the impact of a suboptimal
      selenium status on the hepatic metabolome of male mice analyzed by a targeted
      liquid chromatography/tandem mass spectrometry and a method based on non-targeted
      gas chromatography hyphenated with mass spectrometry. Feeding animals a diet with
      about half of the recommended selenium content supplied as selenomethionine
      caused liver glutathione peroxidase and thioredoxin reductase activities to
      decline and lipid peroxidation to increase. Serum T3 thyroid hormone
      concentration also declined via a reduced hepatic deiodinase activity. Metabolite
      profiling revealed predominantly changes in cysteine and carbon-1 metabolism as
      well as in selected lipid subclasses. In particular the concentrations of
      palmitoylcarnitines and oleoylcarnitines (C18:1 and C16:1) and various
      phosphatidylcholine species containing saturated fatty acids were elevated.
      Increased taurine levels suggested an enhanced cysteine flux through the salvage
      pathway whereas increased homocysteine levels appeared to be a consequence of a
      massive down-regulation of cystathionine beta lyase (cystathionine beta synthase)
      and a reduced flux through the transsulfuration pathway. The findings demonstrate
      that a suboptimal selenium status causes alterations in lipid and carbon-1
      metabolism in mouse liver. These changes may contribute to the development of
      diseases associated with a suboptimal selenium status.

PMID- 24917046
TI  - Capsaicin-induced transcriptional changes in hypothalamus and alterations in gut
      microbial count in high fat diet fed mice.
AB  - Obesity is a global health problem and recently it has been seen as a growing
      concern for developing countries. Several bioactive dietary molecules have been
      associated with amelioration of obesity and associated complications and
      capsaicin is one among them. The present work is an attempt to understand and
      provide evidence for the novel mechanisms of anti-obesity activity of capsaicin
      in high fat diet (HFD)-fed mice. Swiss albino mice divided in three groups (n=8
      10) i.e. control, HFD fed and capsaicin (2mg/kg, po)+HFD fed were administered
      respective treatment for 3months. After measuring phenotypic and serum related
      biochemical changes, effect of capsaicin on HFD-induced transcriptional changes
      in hypothalamus, white adipose tissue (WAT) (visceral and subcutaneous), brown
      adipose tissue (BAT) and gut microbial alterations was studied and quantified.
      Our results suggest that, in addition to its well-known effects, oral
      administration of capsaicin (a) modulates hypothalamic satiety associated
      genotype, (b) alters gut microbial composition, (c) induces "browning" genotype
      (BAT associated genes) in subcutaneous WAT and (d) increases expression of
      thermogenesis and mitochondrial biogenesis genes in BAT. The present study
      provides evidence for novel and interesting mechanisms to explain the anti
      obesity effect of capsaicin. 

PMID- 24917043
TI  - MC1R variants increased the risk of sporadic cutaneous melanoma in darker
      pigmented Caucasians: a pooled-analysis from the M-SKIP project.
AB  - The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the
      association between MC1R variants and the risk of sporadic cutaneous melanoma
      (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin
      cancer and phenotypic characteristics. Data included 5,160 cases and 12,119
      controls from 17 studies. We calculated a summary odds ratio (SOR) for the
      association of each of the nine most studied MC1R variants and of variants
      combined with CM by using random-effects models. Stratified analysis by
      phenotypic characteristics were also performed. Melanoma risk increased with
      presence of any of the main MC1R variants: the SOR for each variant ranged from
      1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any
      MC1R variant had a 66% higher risk of developing melanoma compared with wild-type
      subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants
      was 28%. When taking into account phenotypic characteristics, we found that MC1R
      associated melanoma risk increased only for darker-pigmented Caucasians: SOR
      (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin
      Type III/IV. Our study documents the important role of all the main MC1R variants
      in sporadic CM and suggests that they have a direct effect on melanoma risk,
      independently on the phenotypic characteristics of carriers. This is of
      particular importance for assessing preventive strategies, which may be directed
      to darker-pigmented Caucasians with MC1R variants as well as to lightly
      pigmented, fair-skinned subjects. 

PMID- 24917047
TI  - Extra virgin olive oil intake delays the development of amyotrophic lateral
      sclerosis associated with reduced reticulum stress and autophagy in muscle of
      SOD1G93A mice.
AB  - Amyotrophic lateral sclerosis is a neurodegenerative disease associated with
      mutations in antioxidant enzyme Cu/Zn-superoxide dismutase 1. Albeit there is no
      treatment for this disease, new insights related to an exacerbated lipid
      metabolism have been reported. In connection with the hypermetabolic lipid
      status, the hypothesis whether nature of dietary fat might delay the progression
      of the disease was tested by using a transgenic mouse that overexpresses the
      human SOD1G93A variant. For this purpose, SOD1G93A mice were assigned randomly to
      one of the following three experimental groups: (1) a standard chow diet
      (control, n=21), (2) a chow diet enriched with 20% (w/w) extra virgin olive oil
      (EVOO, n=22) and (3) a chow diet containing 20% palm oil (palm, n=20). They
      received the diets for 8 weeks and the progression of the disease was assessed.
      On the standard chow diet, average plasma cholesterol levels were lower than
      those mice receiving the high-fat diets. Mice fed an EVOO diet showed a
      significant higher survival and better motor performance than control mice. EVOO
      group mice survived longer and showed better motor performance and larger muscle
      fiber area than animals receiving palm. Moreover, the EVOO-enriched diet improved
      the muscle status as shown by expression of myogenic factors (Myod1 and Myog) and
      autophagy markers (LC3 and Beclin1), as well as diminished endoplasmic reticulum
      (ER) stress through decreasing Atf6 and Grp78. Our results demonstrate that EVOO
      may be effective in increasing survival rate, improving motor coordination
      together with a potential amelioration of ER stress, autophagy and muscle damage.

PMID- 24917049
TI  - The Patella Pro study - effect of a knee brace on patellofemoral pain syndrome:
      design of a randomized clinical trial (DRKS-ID:DRKS00003291).
AB  - BACKGROUND: Patellofemoral pain syndrome (PFPS) is a frequent cause of anterior
      knee pain predominantly affecting young female patients who do not have
      significant chondral damage. Development of PFPS is probably multifactorial,
      involving various knee, hip, and foot kinematic factors. Biomechanical studies
      have described patellar maltracking and dynamic valgus (functional malalignment)
      in patients with patellofemoral pain syndrome. The literature provides evidence
      for short-term use of nonsteroidal anti-inflammatory drugs; short-term medially
      directed taping; and exercise programs focusing on the lower extremity, hip, and
      trunk muscles. Evidence supporting the use of patellar braces is limited because
      previous studies have been low quality. The aim of this article is to publish the
      design of a prospective randomized trial that examines the outcomes of patients
      with PFPS after treatment with a new patellar brace (Patella Pro) that applies
      medially directed force on the patella. METHODS/DESIGN: For this multicenter
      trial, 156 patients (adolescents and young adults) with PFPS were recruited from
      orthopedic practices and orthopedic hospitals and randomly allocated to 3 months
      of supervised physiotherapy in combination with the Patella Pro brace or
      supervised physiotherapy alone. The primary outcome measures are pain (numerical
      analog scale); knee function (Kujala score and Knee Injury and Osteoarthritis
      Outcome Score); and self-reported perception of recovery at baseline, 6 weeks, 3
      months, and 1 year. DISCUSSION: Only limited evidence for the use of a patellar
      brace for the treatment of PFPS exists in the literature. Disputable evidence for
      the use of orthoses for PFPS patients has been presented in one meta-analysis, in
      which only one of three studies found the effect of a medially directed patellar
      brace to be significant. Because of these low-quality studies, the authors
      concluded that this evidence should be regarded as limited, and we feel there is
      a need for further well-designed studies to evaluate the effect of patellar
      bracing on PFPS-related pain. The Patella Pro study is a prospective randomized
      trial in which supervised physiotherapy in combination with a patellar brace is
      compared with supervised physiotherapy alone. This trial started in April 2012
      and finished in October 2013. TRIAL REGISTRATION: DRKS-ID:DRKS00003291, January
      3rd, 2012.

PMID- 24917050
TI  - Retrieval speeds context fluctuation: why semantic generation enhances later
      learning but hinders prior learning.
AB  - In recent work, retrieval has been shown to enhance memory for events following
      that retrieval. In this set of experiments, we examined the effects of
      interleaved semantic retrieval on both previous and future learning within a
      multilist learning paradigm. Interleaved retrieval led to enhanced memory for
      lists learned following retrieval. In contrast, memory was impaired for lists
      learned prior to retrieval (Experiment 1). These results are consistent with
      recent work in multilist learning, directed forgetting, and list-before-last
      retrieval, all of which indicate a crucial role for retrieval in enhancing mental
      list segregation. This pattern of results follows clearly from a theoretical
      perspective in which retrieval drives internal contextual change and in which
      contextual overlap between study and test promotes better memory. Consistent with
      that perspective, a 15-min delay before the final test eliminated both effects
      (Experiment 2). Experiment 2 replicated the results of Experiment 1 with
      materials and assessments more appropriate for educational settings: Interleaved
      semantic retrieval led learners to be more able to answer questions correctly
      about texts studied after a retrieval event but less able to do so for texts
      studied earlier. 

PMID- 24917051
TI  - Thinking you can catch mental illness: how beliefs about membership attainment
      and category structure influence interactions with mental health category
      members.
AB  - We explored beliefs about mental disorder categories that influence potential
      interactions with category members. Specifically, we investigated beliefs related
      to how membership in a mental disorder category is obtained (communicability and
      causal origin) as well as beliefs related to the underlying reality of disorder
      categories (essentialism and controllability). In Experiment 1, participants'
      interaction-willingness decisions were predicted by their beliefs that a mental
      disorder category was (1) communicable, (2) psychologically caused, (3)
      environmentally caused, and (4) possessed all-or-none membership. With fictitious
      mental disorders, people were less willing to interact with people described as
      having a communicable mental disorder than with those described as possessing any
      of the other factors of interest, highlighting the independent influence of these
      contagion beliefs (Experiment 2). We further explored beliefs about the
      communicability of mental disorders in Experiment 3 by asking participants to
      generate descriptions of how mental disorders are transferred between people. Our
      findings suggest the importance of understanding contagion beliefs in discovering
      why people distance themselves from people diagnosed with mental disorders. More
      generally, our findings help in understanding how our basic category knowledge is
      used to guide interactions with category members, illustrating how knowledge is
      translated into action. 

PMID- 24917052
TI  - Analysis of human serum and whole blood for mineral content by ICP-MS and ICP
      OES: development of a mineralomics method.
AB  - Minerals are inorganic compounds that are essential to the support of a variety
      of biological functions. Understanding the range and variability of the content
      of these minerals in biological samples can provide insight into the
      relationships between mineral content and the health of individuals. In
      particular, abnormal mineral content may serve as an indicator of illness. The
      development of robust, reliable analytical methods for the determination of the
      mineral content of biological samples is essential to developing biological
      models for understanding the relationship between minerals and illnesses. This
      paper describes a method for the analysis of the mineral content of small volumes
      of serum and whole blood samples from healthy individuals. Interday and intraday
      precision for the mineral content of the blood (250 MUL) and serum (250 MUL)
      samples was measured for eight essential minerals--sodium (Na), calcium (Ca),
      magnesium (Mg), potassium (K), iron (Fe), zinc (Zn), copper (Cu), and selenium
      (Se)--by plasma spectrometric methods and ranged from 0.635 to 10.1% relative
      standard deviation (RSD) for serum and 0.348-5.98% for whole blood. A comparison
      of the determined ranges for ten serum samples and six whole blood samples
      provided good agreement with literature reference ranges. The results demonstrate
      that the digestion and analysis methods can be used to reliably measure the
      content of these minerals and potentially of other minerals.

PMID- 24917053
TI  - Percutaneous transesophageal gastro-tubing for management of gastric leakage
      after sleeve gastrectomy.
AB  - Gastric leakage is a challenging complication of sleeve gastrectomy. Multimodal
      approaches, including drainage, clipping, and stenting of the leak, are
      occasionally insufficient. We report successful management of refractory gastric
      leakage using percutaneous transesophageal gastro-tubing (PTEG). Drainage and
      stenting proved inadequate for treating sleeve leakage near the esophagogastric
      junction in two patients. PTEG was finally performed, and enteral feeding was
      started on the following day. The patients were discharged within 1 week. The
      PTEG-tube was removed after confirming oral food intake. Both patients continue
      to do well without recurrence. PTEG was developed for patients who are unsuitable
      for percutaneous endoscopic gastrostomy. PTEG provides decompression and permits
      enteral feeding in patients refractory to other endoscopic treatments. PTEG is an
      option for managing intractable sleeve leakage without surgery. 

PMID- 24917054
TI  - A new flexible plug and play scheme for modeling, simulating, and predicting
      gastric emptying.
AB  - BACKGROUND: In-silico models that attempt to capture and describe the
      physiological behavior of biological organisms, including humans, are
      intrinsically complex and time consuming to build and simulate in a computing
      environment. The level of detail of description incorporated in the model depends
      on the knowledge of the system's behavior at that level. This knowledge is
      gathered from the literature and/or improved by knowledge obtained from new
      experiments. Thus model development is an iterative developmental procedure. The
      objective of this paper is to describe a new plug and play scheme that offers
      increased flexibility and ease-of-use for modeling and simulating physiological
      behavior of biological organisms. METHODS: This scheme requires the modeler
      (user) first to supply the structure of the interacting components and
      experimental data in a tabular format. The behavior of the components described
      in a mathematical form, also provided by the modeler, is externally linked during
      simulation. The advantage of the plug and play scheme for modeling is that it
      requires less programming effort and can be quickly adapted to newer modeling
      requirements while also paving the way for dynamic model building. RESULTS: As an
      illustration, the paper models the dynamics of gastric emptying behavior
      experienced by humans. The flexibility to adapt the model to predict the gastric
      emptying behavior under varying types of nutrient infusion in the intestine
      (ileum) is demonstrated. The predictions were verified with a human intervention
      study. The error in predicting the half emptying time was found to be less than
      6%. CONCLUSIONS: A new plug-and-play scheme for biological systems modeling was
      developed that allows changes to the modeled structure and behavior with reduced
      programming effort, by abstracting the biological system into a network of
      smaller sub-systems with independent behavior. In the new scheme, the modeling
      and simulation becomes an automatic machine readable and executable task.

PMID- 24917055
TI  - Control of three-dimensional cell adhesion by the chirality of nanofibers in
      hydrogels.
AB  - In the three-dimensional (3D) extracellular matrix (ECM), the influence of
      nanofiber chirality on cell behavior is very important; the helical nanofibrous
      structure is closely related to the relevant biological events. Herein, we
      describe the use of the two enantiomers of a 1,4-benzenedicarboxamide
      phenylalanine derivative as supramolecular gelators to investigate the influence
      of the chirality of nanofibers on cell adhesion and proliferation in three
      dimensions. It was found that left-handed helical nanofibers can increase cell
      adhesion and proliferation, whereas right-handed nanofibers have the opposite
      effect. These effects are ascribed to the mediation of the stereospecific
      interaction between chiral nanofibers and fibronectin. The results stress the
      crucial role of the chirality of nanofibers on cell-adhesion and cell
      proliferation behavior in 3D environments. 

PMID- 24917056
TI  - Survival of the biological control agent Candida sake CPA-1 on grapes under the
      influence of abiotic factors.
AB  - AIMS: As reliability of preharvest applications of biological control agents
      (BCAs) to control fruit pathogens is highly dependent on the survival of the
      selected organism, this study aimed to describe the population dynamics of the
      yeast-BCA Candida sake (Saito & Ota) CPA-1 on grape berries under the effect of
      abiotic factors such as temperature, relative humidity, sunlight and rainfall.
      METHODS AND RESULTS: Candida sake (5 * 10(7) CFU ml(-1)), combined with different
      concentrations of the food additive Fungicover((r)), was applied on grape berry
      clusters. Treated clusters were then exposed to abiotic factors in field or
      laboratory conditions, recovering populations to describe C. sake population
      dynamics. The addition of Fungicover significantly increased C. sake
      multiplication under optimal growth conditions and improved survival under
      fluctuating abiotic factors. After field applications, significant differences in
      populations on grape bunches exposed or covered by fine foliage were detected.
      Simulated rainfall washed off C. sake populations by 0.6-0.9 log units after 20
      mm of rain volume. Allowing populations to establish for 24 h or more, prior to a
      rain event, persistence on grape berries significantly increased and the effect
      of rain intensity was not observable. CONCLUSIONS: Candida sake demonstrated high
      survival ability under unfavourable environmental conditions and persistence
      under intense rain. The study evidenced the importance of the first period just
      after application for C. sake survival on grape tissues and also the protective
      effect of the additive Fungicover. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      research provides new information on the survival of C. sake under field
      conditions and its practical implications for recommending timing of spray with
      this antagonist. Our results could be useful for other yeast antagonists applied
      before harvest. This work, for the first time, defines population dynamics of a
      yeast BCA using simulated rainfall.

PMID- 24917057
TI  - Uncalibrated continuous cardiac output measurement in liver transplant patients:
      LiDCOrapidTM system versus pulmonary artery catheter.
AB  - OBJECTIVE: The aim of the study was to assess the level of agreement between
      continuous cardiac output estimated by uncalibrated pulse-power analysis
      (PulseCOLiR) and intermittent (ICO) and continuous cardiac output (CCO) obtained
      using a pulmonary artery catheter (PAC). DESIGN: Prospective cohort study.
      SETTING: University hospital intensive care unit. PARTICIPANTS: Twenty patients
      after liver transplantation. INTERVENTION: Pulmonary artery catheters were placed
      in all patients, and ICO and CCO were determined using thermodilution. PulseCOLiR
      measurements were made using a LiDCOrapid(TM) (LiDCO Ltd, Cambridge, UK).
      MEASUREMENTS AND MAIN RESULTS: ICO data were determined after intensive care unit
      admission and every 8 hours until the 48th postoperative hour. CCO and PulseCOLiR
      measurements were recorded simultaneously at these same time intervals as well as
      hourly. For the 8-hour data set (140 data pairs), the mean bias and percentage
      errors (PE) were, respectively,-0.10 L/min and 39.2% for ICO versus PulseCOLiR
      and 0.79 L/min and 34.6% for CCO versus PulseCOLiR. For the hourly comparison of
      CCO versus PulseCOLiR (980 data pairs), the bias was 0.75 L/min and the PE 37%.
      To assess the ability to measure change, a 4-quadrant plot was produced for each
      pair of methods. The performance of PulseCOLiR was moderate in detecting changes
      in ICO. CONCLUSIONS: In conclusion, the uncalibrated PulseCOLir method should not
      be used as a substitute for the thermodilution technique for the monitoring of
      cardiac output in liver transplant patients.

PMID- 24917058
TI  - Poor preoperative left ventricular function is associated with decreased insulin
      sensitivity during cardiac surgery.
AB  - OBJECTIVE: To investigate the association between preoperative left ventricular
      ejection function (LVEF) and whole-body insulin sensitivity during cardiac
      surgery. DESIGN: A prospective, non-randomized trial. SETTING: A tertiary care
      hospital setting. PARTICIPANTS: Patients undergoing elective cardiac surgery.
      INTERVENTIONS: Consenting, non-diabetic patients scheduled for elective cardiac
      surgery requiring cardiopulmonary bypass (CPB) were assigned either to a group
      with normal LVEF (EF>=55%) or one with low LVEF (EF<=45%) as assessed by coronary
      angiography. Insulin sensitivity was assessed by the hyperinsulinemic
      normoglycemic clamp technique before and towards the end of CPB. The association
      between LVEF and insulin sensitivity was tested using Student t-test. RESULTS:
      One hundred forty patients were studied, with 48 patients in the low and 92
      patients in the normal LVEF group. Patient demographics were similar in both
      groups except for preoperative LVEF (p<0.001). Before CPB, patients with normal
      LVEF showed higher insulin sensitivity when compared to patients with low LVEF (p
      = 0.04). Insulin sensitivity decreased towards the end of CPB (p<0.001) in both
      groups, resulting in similar values. CONCLUSIONS: Poor preoperative left
      ventricular function is associated with reduced insulin sensitivity before the
      onset of CPB in cardiac surgery.

PMID- 24917059
TI  - Decline in serum hemoglobin in the 7 days after cardiac catheterization.
AB  - OBJECTIVES: Bleeding is an established complication following cardiac
      catheterization and lower preoperative hemoglobin concentration is a potentially
      modifiable risk factor for adverse outcomes after cardiac surgery. However,
      typical changes in serum hemoglobin concentration after cardiac catheterization
      are poorly defined. The authors sought to identify the pattern of change in serum
      hemoglobin concentration within 7 days after cardiovascular catheterization,
      factors associated with this change and any association with adverse outcomes.
      DESIGN: Retrospective observational study over a 1-year period. SETTING: U.S.
      academic medical institution. PARTICIPANTS: Participants were 284 adult patients
      with baseline hemoglobin concentration>=12 g/dL undergoing nonemergent cardiac
      surgery after cardiovascular catheterization via the femoral arterial route.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lowest daily hemoglobin
      concentration was recorded where available for up to 7 days after catheterization
      and before surgery. Generalized estimating equations identified the pattern of
      change in serum hemoglobin while regression models identified factors associated
      with hemoglobin decline. Following cardiovascular catheterization average serum
      hemoglobin declined over time, reaching a nadir 1.4 g/dL (95% CI 1.0-1.8) below
      baseline 6 days after catheterization. A higher baseline hemoglobin concentration
      and lower body mass index were associated with greater maximal decline in
      hemoglobin concentration after catheterization. Acute preoperative hemoglobin
      decline was not associated with acute kidney injury (AKI) or a composite adverse
      outcome that may reflect organ ischemia. CONCLUSIONS: In a cohort of patients
      before cardiac surgery serum hemoglobin declines during the week after cardiac
      catheterization, with maximal average decline observed 5 to 7 days after
      catheterization.

PMID- 24917060
TI  - Cardiopulmonary bypass is associated with altered vascular reactivity of isolated
      pulmonary artery in a porcine model: therapeutic potential of inhaled tezosentan.
AB  - OBJECTIVE: Whereas it is established that endothelin-1 elicits sustained
      deleterious effects on the cardiovascular system during cardiopulmonary bypass
      (CPB), presently it remains unknown whether the inhaled administration of the
      dual ETA and ETB antagonist tezosentan prevents the development of pulmonary
      endothelial dysfunction. DESIGN: A prospective, randomized laboratory
      investigation. SETTING: University research laboratory. PARTICIPANTS: Landrace
      swine. INTERVENTIONS: Three groups of animals underwent a 90-minute period of
      full bypass followed by a 60-minute period of reperfusion. Among treated groups,
      one received tezosentan through inhalation prior to CPB, whereas the other one
      received it intravenously at weaning from CPB; the third group remained
      untreated. Pulmonary vascular reactivity studies, realized on a total of 285
      rings, were performed in all groups, including 1 sham. MEASUREMENTS AND MAIN
      RESULTS: The contractility of pulmonary arteries to prostaglandin F2alpha and to
      the thromboxane A2 mimetic U46619 was preserved in animals submitted to CPB. By
      contrast, there were significant increases both in the maximal contraction to
      endothelin-1 and in the plasma levels of the peptide 60 minutes after
      reperfusion. Tezosentan administered by inhalation or intravenously did not
      prevent the development of pulmonary CPB-associated endothelial dysfunction.
      However, while hemodynamic disturbances were improved with both routes, the
      inhaled administration had a beneficial effect on oxygen parameters over
      intravenous administration. CONCLUSIONS: Despite the blockade of the endothelin-1
      pathway with tezosentan, the development of the pulmonary endothelial dysfunction
      associated with CPB still occurred. However, only the inhalation route had a
      significant impact on gas exchange during CPB.

PMID- 24917061
TI  - Defining fluid responsiveness: a guide to patient-tailored volume titration.

PMID- 24917062
TI  - Electrical bioimpedance cardiography: an old technology with new hopes for the
      future.

PMID- 24917063
TI  - CASE 5-2014 challenging perioperative management of a massive anterior
      mediastinal mass in a symptomatic adult.

PMID- 24917064
TI  - Pro: the total artificial heart: is it an appropriate replacement for existing
      biventricular assist devices?

PMID- 24917065
TI  - In reply to professor Bolsin and colleagues.

PMID- 24917066
TI  - Decreasing end-tidal carbon dioxide in a case of ascending aortic aneurysm.

PMID- 24917067
TI  - Chlamydia Trachomatis and Neisseria Gonorrhoeae prevalence among women of
      reproductive age living in urogenital schistosomiasis endemic area in Ghana.
AB  - BACKGROUND: Many studies have shown an overlap in the epidemiology of sexually
      transmitted infections (STIs) and urogenital schistosomiasis among young women
      living in schistosomiasis endemic areas. Yet we found no study assessing the
      prevalence of STI infections in urogenital schistosomiasis endemic areas in
      Ghana. As part of an epidemiological study on urogenital schistosomiasis and HIV,
      we sought to assess the prevalence of both Chlamydia trachomatis (CT) and
      Neisseria gonorhoeae (NG) infections among women living in schistosomiasis
      endemic communities and explore the relationship between the sexually transmitted
      infections (STIs) and demographic characteristics, sexual behaviour and self
      reported symptoms. METHODS: This was a cross-sectional study in which
      endocervical samples were collected from 191 women aged 15-49 years from October
      2005 to March 2006. Samples were examined for CT and NG using Polymerase Chain
      Reaction (PCR). A structured questionnaire was also used to elicit information on
      study participant's gynaecological and obstetric history and symptoms for genital
      infection. Chi-square test and binary logistic regression were used to assess
      association between CT and NG and other variables such as age, sexual behaviour
      and self-reported symptoms. RESULTS: The overall prevalence of CT and NG were
      6.3% and 2.6% respectively.The highest prevalence rates of CT were in the 15 to
      19 year group while only individuals between 15 and 39 years were positive for
      NG. There was no association between CT and age, contraceptive use and the other
      variables assessed. NG on the other hand was found to be associated with age,
      number of births and number of sexual partners only by chi-square test.
      CONCLUSIONS: Our research revealed higher prevalence of CT and NG infections when
      compared to previous studies conducted among higher risk groups in non-urogenital
      schistosomiasis areas in Ghana. We therefore recommend further studies of these
      STIs in urogenital schistosomiasis endemic areas in the country.

PMID- 24917068
TI  - Polymorphism in gyrA is associated to quinolones resistance in Chilean
      Piscirickettsia salmonis field isolates.

PMID- 24917070
TI  - Identification of FOPDT and SOPDT process dynamics using closed loop test.
AB  - In this paper, identification of stable and unstable first order, second order
      overdamped and underdamped process dynamics with time delay is presented. Relay
      with hysteresis is used to induce a limit cycle output and using this
      information, unknown process model parameters are estimated. State space based
      generalized analytical expressions are derived to achieve accurate results. To
      show the performance of the proposed method expressions are also derived for
      systems with a zero. In real time systems, measurement noise is an important
      issue during identification of process dynamics. A relay with hysteresis reduces
      the effect of measurement noise, in addition a new multiloop control strategy is
      proposed to recover the original limit cycle. Simulation results are included to
      validate the effectiveness of the proposed method. 

PMID- 24917069
TI  - Morphometric analysis of variation in the ribs with age and sex.
AB  - Rib cage morphology changes with age and sex are expected to affect thoracic
      injury mechanisms and tolerance, particularly for vulnerable populations such as
      pediatrics and the elderly. The size and shape variation of the external geometry
      of the ribs was characterized for males and females aged 0-100 years. Computed
      tomography (CT) scans from 339 subjects were analyzed to collect between 2700 and
      10 400 homologous landmarks from each rib. Rib landmarks were analyzed using the
      geometric morphometric technique known as Procrustes superimposition. Age- and
      sex-specific functions of 3D rib morphology were produced representing the
      combined size and shape variation and the isolated shape variation. Statistically
      significant changes in the size and shape variation (P < 0.0001) and shape
      variation (P < 0.0053) of all 24 ribs were found to occur with age in males and
      females. Rib geometry, location, and orientation varied according to the rib
      level. From birth through adolescence, the rib cage experienced an increase in
      size, a decrease in thoracic kyphosis, and inferior rotation of the ribs relative
      to the spine within the sagittal plane. From young adulthood into elderly age,
      the rib cage experienced increased thoracic kyphosis and superior rotation of the
      ribs relative to the spine within the sagittal plane. The increased roundedness
      of the rib cage and horizontal angling of the ribs relative to the spine with age
      influences the biomechanical response of the thorax. With the plane of the rib
      oriented more horizontally, loading applied in the anterior-posterior direction
      will result in increased deformation within the plane of the rib and an increased
      risk for rib fractures. Thus, morphological changes may be a contributing factor
      to the increased incidence of rib fractures in the elderly. The morphological
      functions derived in this study capture substantially more information on
      thoracic skeleton morphology variation with age and sex than is currently
      available in the literature. The developed models of rib cage anatomy can be used
      to study age and sex variations in thoracic injury patterns due to motor vehicle
      crashes or falls, and clinically relevant changes due to chronic obstructive
      pulmonary disease or other diseases evidenced by structural and anatomic changes
      to the chest. 

PMID- 24917071
TI  - Robust adaptive tracking control for nonholonomic mobile manipulator with
      uncertainties.
AB  - In this paper, mobile manipulator is divided into two subsystems, that is,
      nonholonomic mobile platform subsystem and holonomic manipulator subsystem.
      First, the kinematic controller of the mobile platform is derived to obtain a
      desired velocity. Second, regarding the coupling between the two subsystems as
      disturbances, Lyapunov functions of the two subsystems are designed respectively.
      Third, a robust adaptive tracking controller is proposed to deal with the unknown
      upper bounds of parameter uncertainties and disturbances. According to the
      Lyapunov stability theory, the derived robust adaptive controller guarantees
      global stability of the closed-loop system, and the tracking errors and adaptive
      coefficient errors are all bounded. Finally, simulation results show that the
      proposed robust adaptive tracking controller for nonholonomic mobile manipulator
      is effective and has good tracking capacity. 

PMID- 24917072
TI  - Paris polyphylla: chemical and biological prospectives.
AB  - Paris polyphylla J.E. Smith is extensively used in traditional systems of Indian
      and Chinese medicines mainly for its anticancerous property. The national and
      international demand for P. polyphylla is constantly increasing and most of the
      supplies come from wild. Illegal and unscientific exploitation coupled with
      habitat destruction decreases the natural population of the herb, as a
      consequence this species comes under vulnerable category. Restoration and
      conservation of the natural population of this potential herb is prerequisites.
      This article aims to provide an overview on chemical and biological prospective
      of P. polyphylla. Secondary metabolites such as daucosterol, polyphyllin D, beta 
      ecdysterone, Paris saponins I, II, V, VI, VII, H, dioscin, oligosaccharides,
      heptasaccharide, octasaccharide, trigofoenoside A, protogracillin, Paris
      yunnanosides G-J, padelaoside B, pinnatasterone, formosanin C and 20
      hydroxyecdyson saponins have been isolated from P. polyphylla. Several biological
      activities such as anticancerous, antitumor, cytotoxic, anthelmintic,
      antimicrobial, antiangiogenic, immunostimulating, contractile and hemostatic have
      also been reported. Consequently, this review will be helpful to the researcher
      and scientist for further research.

PMID- 24917073
TI  - The Work-Family Interface as a Mediator between Job Demands and Employee
      Behaviour.
AB  - In this investigation, we draw from the job demands-resource model and
      conservation of resources theory to examine the relationship between job demands,
      the work-family interface and worker behaviours. Data collected from an online
      survey of workers revealed that hindrance demands indirectly increase
      interpersonal and organizational deviance through work interference with family
      and family interference with work. Challenge demands indirectly predict
      interpersonal and organizational deviance through work interference with family.
      Finally, hindrance demands indirectly decreased individual-directed
      organizational citizenship behaviours through work-to-family enrichment. Taken
      together, these results stress the relevance of job demand management and
      resource drain/acquisition to counterproductive and extra-role behaviours.

PMID- 24917074
TI  - A prospective observational multicenter study of balloon angioplasty for the
      treatment of native and recurrent coarctation of the aorta.
AB  - OBJECTIVES: Balloon angioplasty (BA) is an important treatment option for
      coarctation of the aorta. The congenital cardiovascular interventional study
      consortium (CCISC) represents a multi-institutional and multi-national effort to
      prospectively investigate congenital cardiac interventions. A prospective
      observational analysis of the efficacy and safety of balloon aortic angioplasty
      was conducted. METHODS: Data were collected prospectively from 36 CCISC sites
      from 2004 to 2012. One hundred and thirty patients underwent BA for native (n =
      76) and recurrent (n = 54) coarctation. Acute, short-term, and intermediate
      outcomes are described for BA performed in the setting of native and recurrent
      coarctation of the aorta. Outcome measures included residual upper to lower
      extremity blood pressure gradient (ULG), use of antihypertensive medications,
      aortic wall injury, reobstruction, and need for reintervention. RESULTS: There
      was no procedural mortality. Acutely in native and recurrent coarctation, BA
      achieved an ULG less than 15 mm Hg in 73-80% and to less than 10 mm Hg in 54-68%
      of patients, respectively. At intermediate follow-up, ULG further improved,
      particularly for those who underwent initial reintervention for recurrent
      coarctation. No significant differences in aortic wall complications were seen
      and intervention free survival was similar for both groups. Following
      angioplasty, there was no significant difference in aortic wall complications;
      however follow up integrated imaging decreased over time. CONCLUSIONS: BA is a
      safe and effective treatment for coarctation of the aorta acutely and at
      intermediate term. Although aortic injury occurred in patients with both native
      and recurrent coarctation, at intermediate follow-up, aneurysm was noted more
      often in those with initial intervention for native coarctation.

PMID- 24917075
TI  - Change in donor artery fractional flow reserve after recanalization of a chronic
      total occlusion: not as impressive as some might have us believe.

PMID- 24917077
TI  - Work-related symptoms in indoor environments: a puzzling problem for the
      occupational physician.
AB  - PURPOSES: People who work indoors often manifest symptoms related to the work
      environment. Sick building syndrome (SBS) is a condition closely associated with
      sealed, air-conditioned workplaces and is especially frequent in countries with a
      cold climate. However, it is also present in Mediterranean countries where
      artificial ventilation accompanies the natural one. The significance of personal
      factors, air quality perception, and psychosocial work conditions in relation to
      SBS and other work-related symptoms needs to be clarified. METHODS: Workers from
      28 companies in the Latium region of Italy were invited to answer a questionnaire
      during their routine medical examination at the workplace. A total of 4,029 out
      of 4,129 took part in the survey, giving a response rate of 97.6 %. RESULTS: A
      high percentage of workers (31.9 %) reported symptoms related to work, and two
      thirds of the employees (65.4 %) complained of environmental problems. In
      logistic regression models, personal factors (gender, smoking habit, age, and
      atopy), anxiety and depression, environmental discomfort and job strain were
      associated both with symptoms of SBS and other work-related symptoms. There was a
      significant association between the perception of stuffy air, dry air, and
      electricity and cases of SBS. Some associations between symptoms and the work
      environment lacked biological plausibility. CONCLUSIONS: The occupational
      physician's task is to systematically monitor workers' symptoms and their
      perception of the work environment in order to analyze this relationship and
      indicates the best mode of preventing illness/discomfort. This paper provides a
      method and reference values.

PMID- 24917078
TI  - Quality-adjusted time without symptoms or toxicity (Q-TWiST): patient-reported
      outcome or mathematical model? A systematic review in cancer.
AB  - OBJECTIVE: Successful cancer treatment is defined as an increase in overall
      survival and/or progression-free survival. Despite their importance, these
      metrics omit patient quality of life. Quality-adjusted time without symptoms or
      toxicity (Q-TWiST) was developed to adjust survival gained, accounting for
      quality of life. The purpose of this systematic review was to assess the methods
      reported in cancer literature to determine Q-TWiST values and how these are
      currently translated to the clinic. METHODS: The Preferred Reporting Items for
      Systematic Reviews and Meta-analyses guidelines were used to conduct a systematic
      review of studies indexed on MEDLINE and Web of Science through April 2013.
      Cancer studies that measured Q-TWiST either as a primary outcome or
      retrospectively and determined utility coefficients from a patient population
      were identified, and their methods reviewed to determine how the utility
      coefficient was calculated. Additionally, other relevant factors such as
      definitions of health states and significant findings were collected and
      summarized. RESULTS: Out of 284 studies, 11 were identified that calculated
      patient-defined utility coefficients. Several methods to determine utility
      coefficients were reported, and multiple definitions of health state toxicity
      were applied. Of these studies, seven reported significant differences (p < 0.05)
      in quality-adjusted survival. No studies, however, directly discussed the
      clinical relevance of their findings. CONCLUSIONS: Currently, Q-TWiST is utilized
      as a mathematical theory rather than a clinical tool. Standardization of
      terminology plus reliability and validity testing of determining both utility
      coefficients and time frame definitions must be performed before Q-TWiST can
      become clinically useful to physicians and patients alike for making treatment
      decisions.

PMID- 24917079
TI  - A highly reactive and enhanced thermal stability nanocomposite catalyst based on
      Au nanoparticles assembled in the inner surface of SiO2 hollow nanotubes.
AB  - A novel hollow tubular SiO2-Au catalyst with a mesoporous structure (HTMS) was
      successfully fabricated by a combination of the sol-gel and calcination
      processes. This method involves the preparation of modified MWCNTs, the
      sequential deposition of Au and then silica layers through the sol-gel processes,
      and finally the calcination at the desired temperature to remove the MWCNTs. The
      obtained samples were characterized by several techniques, such as N2 adsorption
      desorption isotherms, transmission electron microscopy, energy-dispersive X-ray
      spectroscopy analysis, UV-Vis spectra, X-ray diffraction and Thermogravimetric
      Analysis (TGA). The results established that a different calcination temperature
      has an obvious influence on the morphology and structure of the final hollow
      tubular. When the temperature is 550  degrees C, the obtained materials exhibit
      the distinctly tubular structure because of the decomposition of MWCNTs and the
      preservation of hollow tubes. Furthermore, in the catalyst system, the mesoporous
      silica layer can act as the physical barrier to resist the agglomeration and
      sintering of Au nanoparticles even after being subjected to harsh treatments up
      to 650  degrees C. In our experiments, the catalytic activities of HTMS SiO2-Au
      were investigated by photometrically monitoring the reduction of p-nitrophenol (p
      NPh) by an excess of NaBH4. It was found that the prepared HTMS SiO2-Au catalysts
      exhibited a high catalytic activity and this sample could be easily recycled
      without a decrease of the catalytic activities in the reaction. 

PMID- 24917081
TI  - Abstracts for the 3rd International Forum INNOPSY 09 (INNOVATION IN PSYCHIATRY)
      Impact of Early Intervention and Duration of Treatment on the Outcome of
      Psychiatric Disorders Milan, Italy, 18-20 November.

PMID- 24917082
TI  - Loss to follow-up in a cohort of HIV-infected patients in a regional referral
      outpatient clinic in Brazil.
AB  - One of the main aspects related to non-adherence to combined antiretroviral
      therapy (cART) for patients infected with the Human Immunodeficiency Virus (HIV)
      refers to the abandonment of outpatient care. This study was aimed to estimate
      the loss to follow-up in outpatient HIV care at a Regional Referral Clinic (SAE)
      for HIV/AIDS in the city of Juiz de Fora, Brazil, and to identify associated
      factors and predictors. This is a prospective cohort of patients older than 18
      years, under cART and regular outpatient care. The study included patients who
      attended medical visits during July-August 2011. Those who did not return to the
      clinic for new medical appointments within 90 days after the sixth month of
      follow up were considered lost to follow-up in outpatient care. Variables with P
      value <=0.25 in the univariate analysis were included in a logistic regression
      model, adopting a significance level of 0.05. Among the 250 patients included in
      the study, 44 (17.6 %) were lost to follow up in outpatient care. Among these, 38
      (86.4 %) were located in the cART delivery database system (SICLOM). Younger
      patients (<=43 versus >43 years) (OR 2.30 CI 1.06-5.00, P = 0.04), and patients
      attended by physician "E", when compared with physicians "A", "B", "C" or "D" (OR
      5.90 CI 2.64-13.18, P = 0.00) were more likely to be lost to follow-up. Patients
      admitted in the service for 7 years or more were also more likely to be to lost
      to follow-up (OR 2.27 CI 1.2-4.4, P = 0.01), although this association did not
      remain statistically significant in the multivariate analysis. Although the
      purpose of the study, to identify individual factors associated to loss to follow
      up, positives associations with a specific physician and with patients admitted
      in the service for 7 years or more suggest organizational factors. Although the
      majority of patients lost to follow-up in outpatient care were detected by
      SICLOM, a detectable viral load in most of these patients suggest a quality of
      outpatient HIV care proved ineffective, despite the availability of cART. We
      conclude on the need for further studies to investigate structural factors
      associated to loss to follow-up when enhanced retention strategies should be
      implemented in order to maintain an effective outpatient HIV care.

PMID- 24917080
TI  - Efficacy and safety of fractional carbon dioxide laser for treatment of unwanted
      facial freckles in phototypes II-IV: a pilot study.
AB  - Facial freckles are a cosmetic concern to Egyptians, particularly young females.
      Several therapeutic lines exist with variable response rates and limitations.
      Fractional carbon dioxide (FCO2) laser provides minimal ablation and therefore
      less down time and less side effects. The efficacy and safety of this laser
      technology have still not been studied in freckles. The aim of this study is to
      assess the efficacy and safety of FCO2 laser in the treatment of unwanted facial
      freckles in Egyptians. Twenty patients undergone a single session of FCO2 laser
      and then were followed up clinically a month later. Photographs were taken before
      treatment and at follow-up visit and were assessed by three blinded
      investigators. Percent of global improvement was measured on a 4-point grading
      scale. Patient's satisfaction and adverse events were recorded. Two patients (10
      %) showed grade 1 improvement, while eight patients (40 %) showed grade 2
      improvement. Nine patients (45 %) showed grade 3 improvement, and only one
      patient (5 %) showed grade 4 improvement. FCO2 laser resurfacing is effective and
      safe in treatment of facial freckles in skin phototypes II-IV. It can offer a
      more practical alternative to topical treatments, and a cheaper alternative to Q
      switched lasers. 

PMID- 24917083
TI  - 2012 American Geriatrics Society Beers criteria: enhanced applicability for
      detecting potentially inappropriate medications in European older adults? A
      comparison with the Screening Tool of Older Person's Potentially Inappropriate
      Prescriptions.
AB  - OBJECTIVES: To determine the prevalence of potentially inappropriate medications
      (PIMs) and related factors through a comparative analysis of the Screening Tool
      of Older Person's Potentially Inappropriate Prescriptions (STOPP), the 2003 Beers
      criteria, and the 2012 AGS update of the Beers criteria. DESIGN: Cross-sectional.
      SETTING: Primary care. PARTICIPANTS: Community-dwelling persons aged 65 and older
      who live on the island of Lanzarote, Spain (N = 407). MEASUREMENTS:
      Sociodemographic characteristics; independence in activities of daily living;
      cognitive function; Geriatric Depression Scale; clinical diagnoses; and complete
      data on indication, dosage, and length of drug treatments. One thousand eight
      hundred seventh-two prescriptions were examined, and the rate of PIMs was
      assessed with the three criteria. The primary endpoint was the percentage of
      participants receiving at least one PIM. Multivariate logistic regression was
      used to examine the factors related to PIMs. RESULTS: Potentially inappropriate
      medications were present in 24.3%, 35.4%, and 44% of participants, according to
      the 2003 Beers criteria, STOPP, and 2012 Beers criteria, respectively. The
      profile of PIMs was also different (the most frequent being benzodiazepines in
      both Beers criteria lists and aspirin in the STOPP). The number of drugs was
      associated with risk of prescribing PIMs in all three models, as was the presence
      of a psychological disorder in the 2003 Beers criteria (odds ratio (OR) = 2.07,
      95% confidence interval (CI) = 1.26-3.40) and the 2012 Beers criteria (OR = 2.91,
      95% CI = 1.83-4.66). The kappa for degree of agreement between STOPP and the 2012
      Beers criteria was 0.35 (95% CI = 0.25-0.44). CONCLUSION: The 2012 Beers criteria
      detected the highest number of PIMs, and given the scant overlapping with the
      STOPP criteria, the use of both tools may be seen as complementary.

PMID- 24917084
TI  - Confirmation that "Brachyspira hampsonii" clade I (Canadian strain 30599) causes
      mucohemorrhagic diarrhea and colitis in experimentally infected pigs.
AB  - BACKGROUND: "Brachyspira hampsonii", discovered in North America in 2010
      associated with dysentery-like illness, is an economically relevant swine
      pathogen resulting in decreased feed efficiency and increased morbidity,
      mortality and medication usage. "B. hampsonii" clade II strain 30446 has been
      shown to be causally associated with mucohemorrhagic diarrhea and colitis. Our
      objectives were to determine if "Brachyspira hampsonii" clade I strain 30599 is
      pathogenic to pigs, and to evaluate the relative diagnostic performance of three
      ante mortem sampling methodologies (direct PCR on feces, PCR on rectal GenoTube
      Livestock swabs, Brachyspira culture from rectal swabs). Five-week old pigs were
      intragastrically inoculated thrice with 108 genomic equivalents "B. hampsonii" (n
      = 12), or served as sham controls (n = 6). Feces were sampled and consistency
      assessed daily. Necropsies were performed 24 h after peak clinical signs.
      RESULTS: One pig died due to unrelated illness. Nine of 11 inoculated pigs, but
      no controls, developed mucoid or mucohemorrhagic diarrhea (MHD). Characteristic
      lesions of swine dysentery were observed in large intestine. "B. hampsonii"
      strain 30599 DNA was detected by qPCR in feces of all inoculated pigs for up to 6
      days prior to the onset of MHD. The organism was isolated from the feces and
      colons of pigs demonstrating MHD, but not from controls. B. intermedia was
      isolated from inoculated pigs without MHD, and from 5 of 6 controls. CONCLUSIONS:
      We conclude that "Brachyspira hampsonii" clade I strain 30599 is pathogenic and
      causes mucohemorrhagic diarrhea and colitis in susceptible pigs. Moreover, the
      three sampling methodologies performed similarly. GenoTube Livestock, a forensic
      swab designed to preserve DNA during shipping is a useful tool especially in
      settings where timely transport of diagnostic samples is challenging.

PMID- 24917085
TI  - Usefulness of video-EEG in the paediatric emergency department.
AB  - Over the past two decades the EEG has technically improved from the use of analog
      to digital machines and more recently to video-EEG systems. Despite these
      advances, recording a technically acceptable EEG in an electrically hostile
      environment such as the emergency department (ED) remains a challenge,
      particularly with infants or young children. In 1996, a meeting of French experts
      established a set of guidelines for performing an EEG in the ED based on a review
      of the available literature. The authors highlighted the most suitable
      indications for an emergency EEG including clinical suspicion of cerebral death,
      convulsive and myoclonic status epilepticus, focal or generalized relapsing
      convulsive seizures as well as follow-up of known convulsive patients. They
      further recommended emergency EEG in the presence of doubt regarding the
      epileptic nature of the presentation as well as during the initiation or
      modification of sedation following brain injury. Subsequently, proposals for
      expanding the use of EEG in emergency patients have been advocated including
      trauma, vascular and anoxic-ischemic injury due to cardiorespiratory arrest,
      postinfective encephalopathy and nonconvulsive status epilepticus. The aim of
      this review is to show the diagnostic importance of video-EEG, as well as
      highlighting the predictive prognostic factors for positive and negative
      outcomes, when utilized in the pediatric ED for seizures as well as other
      neurological presentations. 

PMID- 24917088
TI  - Similar but different: the importance of context.

PMID- 24917086
TI  - Effects of camptothecin derivatives and topoisomerase dual inhibitors on
      Trypanosoma cruzi growth and ultrastructure.
AB  - BACKGROUND: Trypanosoma cruzi is the etiological agent of Chagas' disease that is
      an endemic disease in Latin America and affects about 8 million people. This
      parasite belongs to the Trypanosomatidae family which contains a single
      mitochondrion with an enlarged region, named kinetoplast that harbors the
      mitochondrial DNA (kDNA). The kinetoplast and the nucleus present a great variety
      of essential enzymes involved in DNA replication and topology, including DNA
      topoisomerases. Such enzymes are considered to be promising molecular targets for
      cancer treatment and for antiparasitic chemotherapy. In this work, the
      proliferation and ultrastructure of T. cruzi epimastigotes were evaluated after
      treatment with eukaryotic topoisomerase I inhibitors, such as topotecan and
      irinotecan, as well as with dual inhibitors (compounds that block eukaryotic
      topoisomerase I and topoisomerase II activities), such as baicalein, luteolin and
      evodiamine. Previous studies have shown that such inhibitors were able to block
      the growth of tumor cells, however most of them have never been tested on
      trypanosomatids. RESULTS: Considering the effects of topoisomerase I inhibitors,
      our results showed that topotecan decreased cell proliferation and caused
      unpacking of nuclear heterochromatin, however none of these alterations were
      observed after treatment with irinotecan. The dual inhibitors baicalein and
      evodiamine decreased cell growth; however the nuclear and kinetoplast
      ultrastructures were not affected. CONCLUSIONS: Taken together, our data showed
      that camptothecin is more efficient than its derivatives in decreasing T. cruzi
      proliferation. Furthermore, we conclude that drugs pertaining to a certain class
      of topoisomerase inhibitors may present different efficiencies as
      chemotherapeutical agents.

PMID- 24917087
TI  - The cost of treating severe refractory asthma in the UK: an economic analysis
      from the British Thoracic Society Difficult Asthma Registry.
AB  - Severe refractory asthma poses a substantial burden in terms of healthcare costs
      but relatively little is known about the factors which drive these costs. This
      study uses data from the British Thoracic Society Difficult Asthma Registry
      (n=596) to estimate direct healthcare treatment costs from an National Health
      Service perspective and examines factors that explain variations in costs. Annual
      mean treatment costs among severe refractory asthma patients were L2912 (SD
      L2212) to L4217 (SD L2449). Significant predictors of costs were FEV1% predicted,
      location of care, maintenance oral corticosteroid treatment and body mass index.
      Treating individuals with severe refractory asthma presents a substantial cost to
      the health service. 

PMID- 24917089
TI  - Sustainability in clinical skills teaching.
AB  - BACKGROUND: The deleterious effects of climate change mean that environmental
      sustainability is increasingly becoming a moral and economic necessity.
      Consequently, clinicians will increasingly be called upon to manage the effects
      of health care on climate change, and they must therefore do as much as is
      practically possible to limit the negative effects of their practice on the
      environment. As medical educators we have the opportunity not only to reduce the
      environmental impact of our own clinical practice, but also that of those who we
      teach, through innovation. Such novelty can be explored during student-selected
      components (SSCs). Clinicians will increasingly be called upon to manage effects
      of health care on climate change CONTEXT: The project, entitled 'Can we introduce
      sustainability to clinical skills teaching?' was led by two third-year medical
      students during their SSC periods. New ways to make existing skills more
      sustainable were explored by surveying existing practice in the workplace,
      analysing selected skills in a lab-based setting and through discussions with
      sustainability champions. INNOVATION: Cannulation and intravenous (IV) antibiotic
      preparation were chosen by the students as prototype skills. These skills were
      observed by the students in the workplace and adapted by them to appease the
      'triple bottom line' of sustainability: environmental, social and economic
      factors were addressed. The revised skills were taught by the students to their
      peers in a sustainably conscious fashion. IMPLICATIONS: Provided that such
      innovations in sustainable skills teaching are deemed appropriate by clinical
      skills directors, such methods could be adopted across medical schools and
      expanded to cover a wider range of skills.

PMID- 24917090
TI  - Observing trainee encounters using a one-way mirror.
AB  - BACKGROUND: Direct observation of patient encounters is a key component of
      evaluating residents during training, but there are scarce data on the various
      methods of observation. AIM: To implement a novel method for direct observation
      of out-patient encounters via a one-way mirror in an internal medicine resident
      practice, and to assess the feasibility and acceptance of this method. METHODS:
      Each selected resident-patient encounter was directly observed by a preceptor
      through a one-way mirror. The preceptor provided feedback to the resident at the
      conclusion of each encounter. A post-visit survey assessed resident satisfaction
      and comfort with this method of observation. RESULTS: Using a one-way mirror was
      a feasible method of observation. Fifty residents had a clinic visit that was
      directly observed, and 42 (84%) completed the post-visit survey. Residents
      reported that they preferred direct observation through a one-way mirror compared
      with other methods, including videotaped encounters or having a preceptor
      physically present in the room. They also felt that having a preceptor observing
      through the one-way mirror had no negative effect on the clinic visit. Direct
      observation of patient encounters is a key component of evaluating residents
      CONCLUSIONS: Direct observation through a one-way mirror is a viable method in
      the out-patient setting, and might be preferable for evaluating certain skills.

PMID- 24917091
TI  - Musculoskeletal pareidolia in medical education.
AB  - BACKGROUND: Medical educators use a variety of strategies to help medical
      students and resident doctors understand and remember complex topics. METHODS:
      One teaching tool is matching up radiographic appearances with unrelated, common,
      non-medical images, in order to help students easily recognise clinical patterns.
      DISCUSSION: However, even among medical educators who use this approach, many are
      not aware of the neuropsychiatric phenomenon they are using, known as pareidolia.
      We will describe pareidolia (a form of patternicity) and give two examples of its
      use in the clinical teaching of musculoskeletal imaging abnormalities: the
      winking owl and the Scottie dog.

PMID- 24917092
TI  - Medical students in gynaecology clinics.
AB  - OBJECTIVE: This study aimed to investigate factors that influence a patient's
      acceptance of a medical student's involvement in their consultation when
      attending a public hospital gynaecology clinic. Factors that influence a
      patient's acceptance of a medical student's involvement in a consultation
      METHODS: This was an observational study of women attending gynaecology clinics
      at Royal Prince Alfred Hospital (RPAH) from January to December 2011. The
      questionnaire sought demographic information and asked women about their
      knowledge of medical student attendance at the clinics, if they would allow a
      student to be present during their consultation and whether they would allow a
      student to examine them. It also sought reasons for their responses. RESULTS: Of
      the 460 questionnaires distributed, 97 per cent (446) were completed. Overall,
      85.6 per cent (382) of patients expressed an acceptance of medical students being
      present in their consultation, and 63.9 per cent (285) said they would allow
      students to examine them. Factors significantly associated with an increased
      acceptance of examination by medical students included being aware that a student
      may be present (p=0.003), and being married or in a committed relationship
      (p=0.023). Age and education level were not significantly associated with
      acceptance of being examined by a student, and ethnicity was too diverse to
      assess any possible bias. All groups maintained a preference for female students.
      CONCLUSION: This study has found that being aware that medical students may be
      present in gynaecology clinics may increase patient acceptance of being examined
      by a student. This demonstrates a role for information to be distributed to
      patients prior to their appointment to facilitate medical training.

PMID- 24917093
TI  - Peer-teaching of evidence-based medicine.
AB  - BACKGROUND: Many medical schools teach the principles of evidence-based medicine
      (EBM) as part of their undergraduate curriculum. Medical students perceive that
      EBM is valuable to their undergraduate and postgraduate career. Students may
      experience barriers to applying EBM principles, especially when searching for
      evidence or identifying high-quality resources. CONTEXT: The UK National
      Institute for Health and Care Excellence (NICE) Evidence Search is a service that
      enables access to authoritative clinical and non-clinical evidence and best
      practice through a web-based portal. INNOVATION: Evidence-based medicine
      workshops were organised and delivered by fourth-year medical students, having
      first received training from NICE to become NICE student champions. The workshops
      covered the basic principles of EBM and focused on retrieving EBM resources for
      study through the NICE Evidence Search portal. The scheme was evaluated using a
      pre-workshop survey and an 8-12 week post-workshop survey. Self-reported
      confidence in searching for evidence-based resources increased from 29 per cent
      before the workshop to 87 per cent after the workshop. Only 1 per cent of
      students rated evidence-based resources as their first preference pre-workshop,
      compared with 31 per cent post-workshop. IMPLICATIONS: The results show that
      although many students were aware of evidence-based resources, they tended not to
      use them as their preferred resource. Despite appreciating the value of evidence
      based resources, few students were confident in accessing and using such
      resources for pre-clinical study. A peer-taught workshop in EBM improved
      students' confidence with, and use of, evidence-based resources.

PMID- 24917094
TI  - The role of social media in clinical excellence.
AB  - BACKGROUND: The provision of excellent patient care is a goal shared by all
      doctors. The role of social media (SM) in helping medical students and doctors
      achieve clinical excellence is unknown. Social media may help facilitate the
      achievement of clinical excellence PURPOSE: This report aimed to identify
      examples of how SM may be used to help promote the achievement of clinical
      excellence in medical learners. METHODS: Three of the authors previously
      conducted a systematic review of the published literature on SM use in
      undergraduate, graduate and continuing medical education. Two authors re-examined
      the 14 evaluative studies to identify any examples of SM use that may facilitate
      the achievement of clinical excellence and to consider whether there were any
      aspects of clinical excellence for which no studies had been performed, and, if
      so, whether SM was relevant to these domains. RESULTS: Each study touched on one
      or more of the following domains of clinical excellence: communication and
      interpersonal skills; professionalism and humanism; knowledge; diagnostic acumen;
      exhibiting a passion for patient care; a scholarly approach to clinical practice;
      and explicitly modelling expertise to medical trainees. No study addressed the
      role of SM to promote the skillful negotiation of the health care system, and in
      collaboration with investigators to advance science and discovery; however,
      additional evidence suggested that SM may play an adjunctive role in promoting
      the achievement of these aspects of clinical excellence. CONCLUSION: This report
      supports the hypothesis that SM may help facilitate the achievement of clinical
      excellence; however, further research is needed into the role of SM in promoting
      the achievement of clinical excellence.

PMID- 24917095
TI  - Teledebriefing: connecting learners to faculty members.
AB  - BACKGROUND: Simulation has become widespread among medical educators. Although
      simulation facilities are available at most teaching institutions, the number of
      qualified instructors to facilitate post-simulation debriefing is inadequate,
      resulting in sub-par educational experiences for learners. CONTEXT: Efforts to
      broaden medical curricula to include simulation have been successful. An integral
      component of simulation-based education is the debriefing stage, in which
      learning and reflection are believed to be greatest. To be maximally effective,
      debriefing should be performed by faculty members who have both expertise in the
      subject matter and a strong grasp of debriefing principles. Unfortunately, the
      debriefing portion of simulation exercises is often performed in a sub-par
      fashion because many simulation centres do not have access to trained debriefers.
      As a result, the overall experience of simulation training programmes is reduced,
      and the exercises have much less educational benefit to the learner. INNOVATION:
      This article outlines a novel use of videoconferencing technology for debriefing
      learners at remote locations, which we term teledebriefing. This can be
      accomplished in a cost-effective and straightforward manner using basic
      equipment: a smartphone and a television. Many simulation centres do not have
      access to trained debriefers IMPLICATIONS: Teledebriefing can create a mutually
      beneficial faculty instructor network between institutions. By connecting
      clinical educators from geographically distant areas or from specialties not
      available locally, learners are exposed to faculty that can provide content
      expertise and high-quality debriefing during simulation exercises. Evaluating the
      effectiveness and feasibility of teledebriefing is warranted.

PMID- 24917096
TI  - Evaluation of an online medical teaching forum.
AB  - BACKGROUND: Social media is increasingly being used for teaching and assessment.
      We describe the design and implementation of a Facebook(c) teaching forum for
      medical students, and evaluate its effectiveness. METHODS: A Facebook(c) teaching
      forum was set up in a London Hospital to assist with learning and assessment for
      undergraduate medical students. An independent online survey was used to collate
      their experiences. Accessibility to the forum, usefulness in stimulating peer-to
      peer discussion and the use of weekly formative assessments were evaluated using
      a Likert scale. RESULTS: In total, 91 per cent (n=68/75) of students who had
      Facebook(c) joined the teaching forum. The majority of students completed the
      questionnaire (n=39/68, 57%). All students visited the teaching forum group at
      least once a week. A significant proportion attempted all 10 question sets
      (n=16/39, 41%). Students felt more comfortable asking questions in the forum than
      in ward rounds and clinics (n=22/39, 56%). The general consensus was that
      Facebook(c) could be used for educational purposes, with just 5 per cent of
      students (n=2/39) thinking that Facebook(c) should only be used socially and with
      92 per cent believing that the forum helped to achieve the learning objectives of
      the curriculum (n=36/39). DISCUSSION: Facebook(c) provides a safe environment for
      learning and discussion amongst medical undergraduates undergoing their clinical
      attachments. Furthermore, through formative assessments set by a medical
      educator, it provides a useful revision tool for summative assessments and
      reinforces knowledge learned through conventional teaching methods.

PMID- 24917097
TI  - Written feedback on supervised learning events.
AB  - BACKGROUND: Medical students value constructive feedback, as it helps them to
      improve their performance. Supervised learning events (SLEs) were developed as
      performance assessments and to create opportunities for students to receive
      feedback. Although many would argue the strengths of SLEs, there is a lack of
      literature assessing the quality of written feedback for medical students.
      METHOD: A random sample of Year 4 students at a London medical school provided a
      total of 250 SLE forms for analysis. A coding framework was developed and applied
      to the sample to grade the quality of the feedback. RESULTS: Overall, 63.1 per
      cent of feedback entries were graded weak. More of the 'areas for improvement'
      comments were graded weak (73.6%) compared with the 'points of good performance'
      (52.8%). Of the feedback graded weak, many were left blank (40.6%), were non
      specific (34.1%), only used words such as 'keep practising' (19.5%), were
      irrelevant (4.6%) or were illegible (1.2%). CONCLUSION: The quality of written
      feedback is clearly an area for development. Factors that impede this include a
      lack of time and the fact that some assessors may be uncomfortable providing
      negative feedback. In order to improve, it is important that both students and
      assessors are trained more thoroughly in giving effective written feedback. The
      quality of written feedback is clearly an area for development.

PMID- 24917098
TI  - Online assessment: what influences students to engage with feedback?
AB  - BACKGROUND: The intention of giving written feedback is to close the gap between
      the standard achieved and the standard desired, but students do not always read
      it. Web-based marking tools are increasingly being used in assessment practices
      to deliver the feedback. What motivates students to read the feedback provided,
      especially since the advent of these online marking tools, is poorly understood.
      This research looked at the factors likely to influence a medical student's
      engagement with written feedback delivered through an online marking tool
      (grademark by Turnitin). What motivates students to read the feedback provided
      METHODS: Third-year medical students on a UK undergraduate medical course
      submitted an assignment online. A questionnaire was distributed to a cohort of
      them following the release of their results and feedback, allowing quantitative
      and qualitative data collection. Software recorded whether they opened their
      feedback. Previous examination performance figures were also collated. RESULTS:
      Online feedback is accessible and acceptable to the majority of students.
      Personal demographics, computer literacy, previous course performance, or
      personal motivational drivers did not predict those who did or did not read it.
      Some students reported seeing little value in feedback because of their previous
      negative experiences. A minority found feedback hurtful, and were likely to show
      avoidance behaviours. DISCUSSION: This research found that feedback provided
      through an online marking tool overcame many of the problems associated with
      handwritten feedback, but alone was not enough to ensure universal engagement.
      Feedback dialogues are proposed as a method to overcome negative student
      experiences, enhance tutor performance and encourage future student engagement.

PMID- 24917099
TI  - Interprofessional learning for medication safety.
AB  - BACKGROUND: Patient safety is a worldwide priority. Recommendations have been
      made that doctors, nurses and pharmacists could interact more effectively to
      improve patient outcomes, and that interprofessional education should be
      encouraged. In 2009, the North East Strategic Health Authority awarded Workforce
      Development Initiative funding to Northumbria Healthcare National Health Service
      (NHS) Foundation Trust to develop an undergraduate interprofessional training
      activity in medication safety for medicine, pharmacy and nursing students.
      CONTEXT: Interprofessional seminars for medication safety and therapeutics were
      developed that were delivered across the North East of England. The initial
      seminars took place between January and April 2011 at 10 teaching hospitals, and
      were attended by over 400 students (from medicine, pharmacy and nursing).
      INNOVATION: The majority of the workshops were facilitated by an
      interprofessional team comprised of pharmacists, doctors and nurses, with all
      students working in small groups with participants from each of the professional
      groups, where possible. All seminars had standardised materials, but it was up to
      individual facilitators to choose which of the five case studies were used within
      the seminar. The seminars lasted between 2 and 3 hours, and depending on which
      case studies were used, two or three cases could be discussed. Student feedback
      showed that the seminar was particularly successful in highlighting and improving
      the students' understanding of each other's roles and responsibilities in
      relation to medication safety. There are considerable organisational challenges
      in arranging interprofessional groups. Scenarios need to provide tasks that
      engage and challenge all of the professions involved. Facilitation is an
      important element. Interprofessional education should be encouraged.

PMID- 24917100
TI  - A guide for interprofessional case presentations.
AB  - BACKGROUND: Opportunities for interprofessional learning (IPL) and the promotion
      of interprofessional (IP) communication at the undergraduate level are important
      goals of health science faculties. IPL activities with shared curriculum validity
      to promote full student engagement can be challenging to identify. Case
      presentations that focus on patient-centred learning are one type of activity
      that is likely to have clinical relevance to all undergraduate groups. Guiding
      students and facilitators on this approach using a structured framework is
      necessary to maximise the desired IPL outcomes. CONTEXT: The framework was
      informed by two settings. Firstly, by a large metropolitan health service that
      provided IP clinical placements (ICPs). Six 2-week placements in aged care
      rehabilitation were completed by medical, nursing and allied health students
      Secondly, by a an inner Melbourne private hospital where weekly IP case
      presentations were established. INNOVATION: The innovation was a framework
      developed by clinical teachers and academics across two health services to guide
      facilitators and students participating in an IP case presentation. IMPLICATIONS:
      This framework, highlighting both strategies for success and potential pitfalls,
      may provide a guide to teachers wishing to establish student IP case
      presentations within their health service or clinical placement context. The
      deployment and use of this framework may then provide a basis to evaluate IP case
      based presentations for formative or summative student assessment.

PMID- 24917101
TI  - The expert patient as teacher: an interprofessional Health Mentors programme.
AB  - BACKGROUND: To meet future health care needs, medical education must increase the
      emphasis on chronic illness care, interprofessional teamwork, and working in
      partnership with patients and families. One way to address these needs is to
      involve patients as teachers in longitudinal interprofessional educational
      programmes grounded in principles of patient-professional partnerships and shared
      decision-making. CONTEXT: The University of British Columbia has a history of
      initiatives designed to bring patient and community voices into health
      professional education. Increasing opportunities for interprofessional education
      has become important because of accreditation requirements. INNOVATION: We
      describe preliminary findings from a 3-year pilot of an interprofessional Health
      Mentors programme, an elective patient-as-teacher initiative in which groups of
      four students from different disciplines learn together, with and from a mentor
      with a chronic condition (an 'expert by experience') over three semesters. The
      goals, achieved through six themed meetings and a symposium, are to learn about
      living with a chronic condition from the patient's perspective and to develop
      interprofessional competencies. Groups are given suggested topics for each
      meeting, but function as self-managed learning communities, and are encouraged to
      explore their own questions. Faculty members support direct learning between
      students and mentors through setting broad objectives and responding to the
      student reflections written after each group meeting. Students and mentors rate
      the programme highly, and a wide range of important learning outcomes have been
      documented. Medical education must increase the emphasis on chronic illness care,
      working in partnership with patients IMPLICATIONS: Key characteristics,
      generalisable to other educational programmes, include the role of faculty staff
      in supporting learning between students and patients, a minimalist structure to
      promote ownership and creativity, and flexible delivery.

PMID- 24917102
TI  - Medical school choice: what influences applicants?
AB  - BACKGROUND: Little is known about factors influencing applicants' choice of
      medical school, yet it is important that both the academic and non-academic needs
      of medical students are satisfied, and that medical schools attract students
      suited to the courses provided. Relevant evidence suggests that there are five
      main factors influencing choice: curriculum; reputation of the school; personal
      contact; location; and facilities. Aberdeen has the particular challenge of being
      the most northern medical school in the UK. METHOD: To address this challenge,
      and learning from the literature, a medical school open day was developed to
      showcase the medical school, the wider university and the city of Aberdeen.
      RESULTS: The main messages from this small study were that interactive events
      were more popular than static displays, and that applicants preferred to interact
      with student representatives rather than just hear about student life, suggesting
      that the opportunity to ask questions and hear the 'uncensored' version of what
      being a student is like are important. DISCUSSION: There are some generalisable
      messages about what prospective students want from an open day, which along with
      the prospectus and the website can contribute to informing choice. Further work
      is needed to identify what is critical in terms of first point of contact, and
      how much this influences the choice of medical school.

PMID- 24917103
TI  - Value of assessment of medical students.

PMID- 24917104
TI  - Early specialty courses and the spiral of learning.

PMID- 24917105
TI  - MedEdPORTAL: a resource for health educators.

PMID- 24917106
TI  - An orchestral metaphor for interprofessional collaborative practice?

PMID- 24917107
TI  - Perspective from a student problem-based learning facilitator.

PMID- 24917108
TI  - Is the keyboard mightier than the pen?

PMID- 24917109
TI  - Response to 'Is the keyboard mightier than the pen?'.

PMID- 24917110
TI  - Teaching ultrasound in a developing country.

PMID- 24917111
TI  - Fibulin-5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse.
AB  - OBJECTIVE: FBLN5 encodes a key protein of elastic fiber matrix assembly and
      function that contributes to maintaining pelvic support and plays the important
      role in the pathophysiology of pelvic organ prolapse (POP). The aim of the study
      was to investigate whether there is an association between common single
      nucleotide polymorphisms (SNPs) of the FBLN5 gene and POP. STUDY DESIGN: A total
      of eleven tag SNPs of the FBLN5 gene were genotyped using the polymerase chain
      reaction with confronting two-pair primers (PCR-CTPP) in 210 patients with POP
      (stages III-IV) and 292 controls with no even minimal POP. RESULTS: We revealed
      significant associations of tag SNPs rs2018736 and rs12589592 with POP. The top
      association signal was found for SNP rs2018736 (protective effect for the minor
      allele A) in the entire set: p=0.0026, OR=0.42, 95% CI: 0.24-0.75; in the stratum
      with pelvic floor trauma: p=0.0018, OR=0.27, 95% CI: 0.11-0.64; and in the
      stratum with fetal macrosomia: p=0.013, OR=0.14, 95% CI: 0.03-0.71. The results
      of the haplotype analyses were consistent with the single SNP analysis. In the
      strata without perineal trauma and fetal macrosomia effects were non-significant,
      possibly, due to the smaller effect sizes. CONCLUSIONS: Current data provide, for
      the first time, strong evidence that common SNPs of the FBLN5 gene are associated
      with POP especially after pelvic floor injury.

PMID- 24917112
TI  - Increasing nontuberculous mycobacteria infection in cystic fibrosis.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) are emerging infections in the CF
      population. AIMS: To assess NTM infection prevalence and associated features in
      our CF clinic population. METHODS: Patient records, 2002-2011, were reviewed for
      NTM infection. FEV1, pancreatic function, sputum microbiology, and serum
      cytokines were compared in patients with and without NTM infection. RESULTS:
      Incidence rate of NTM infection increased from 0 in 2002 to 8.7% in 2011
      (p<0.001). NTM infection prevalence increased 3-fold from 5% (4/79) in 2003 to
      14.5% (16/110) in 2011 (p=0.05). Prevalence of chronic NTM lung disease has
      decreased somewhat since a peak in 2009, with institution of aggressive triple
      therapy. Of NTM-infected compared to uninfected patients, 88.2% vs. 60.3% had a
      known 'severe' CFTR genotype (p=0.04), 88.2% vs. 58.9% were pancreatic
      insufficient (p=0.02); 70.6% vs. 43.8% had chronic Pseudomonas aeruginosa
      (p=0.06); 75% vs. 32% had Aspergillus infection (p=0.007) and 23.5% vs 2.7% had
      allergic bronchopulmonary aspergillosis (p=0.01). Patients infected with
      Mycobacterium abscessus had increased TGF-beta, TNF-alpha, IL-1beta, IL-2, IL-4
      and IL-5 levels (p<0.05). There was no difference in cytokine levels for all NTM
      infected compared to uninfected patients. M. abscessus comprised 46% of all NTM
      infections. Comparing M. abscessus versus other NTM, duration was 10.5 (1-118)
      months versus 1 (1-70) month, median (range) (p=0.004); lung disease occurred in
      69% versus 17% (p=0.0004), with sputum conversion in 4/11 versus 5/6,
      respectively (NS). CONCLUSIONS: NTM incidence and prevalence have increased
      dramatically in our CF clinic, associated with a severe CF genotype and
      phenotype. M. abscessus, the most prevalent NTM, caused prolonged infection
      despite therapy. There has been some decrease in the prevalence of NTM lung
      disease since 2009.

PMID- 24917113
TI  - Lung clearance index during hospital admission in school-age children with cystic
      fibrosis.
AB  - BACKGROUND: There is currently limited information regarding lung clearance index
      (LCI) and its response to treatment of pulmonary exacerbations in CF. We aimed to
      examine the utility of LCI for assessing short term clinical response to IV
      antibiotic therapy in school-age children with CF. METHODS: Subjects experiencing
      exacerbations and hospitalised for IV antibiotics performed both multiple breath
      nitrogen washout (MBNW) and spirometry on admission to hospital and prior to
      discharge. RESULTS: 27 patients (aged 6-20 years) had paired data for MBNW and
      spirometry. Mean LCI reduced from 12.18 to 11.65 (4.4%) by time of discharge and
      FEV1z-score improved from -3.05 to -2.86 (6.2%). Overall, LCI improved in n=15
      (55%) patients compared with n=18 (67%) where FEV1 improved. CONCLUSIONS: In
      summary, these findings do not support the use of LCI (or indeed, FEV1) to gauge
      the short term clinical response to IV antibiotic therapy in school-age children
      with cystic fibrosis.

PMID- 24917114
TI  - Early attained weight and length predict growth faltering better than velocity
      measures in infants with CF.
AB  - BACKGROUND: CF infants often do not grow as expected which adversely affects
      later clinical outcomes, thus sensitive early measures of growth deficiency are
      important. This study compared attained growth for age with velocity standards to
      determine which better predicts growth deficits at 24 months of age. METHODS:
      Growth deficiency in infancy based on weight and length velocity, and attained
      growth was calculated for 1992 infants in the US CF Foundation National Registry
      using the World Health Organization (WHO) and US growth standards. One, two and
      three month increments were used for calculating velocity and pooled for each age
      interval. Sensitivity and specificity of early indicators to predict growth
      deficiency at 24 months were calculated. RESULTS: Observed prevalence of weight
      deficiency (<10th percentile) during the first year of life was 26.8% higher (95%
      CI=(25.6, 28.1%), p<0.001) on average when measured by attained weight for age
      than velocity. Attained weight for age at four months was a more sensitive
      predictor of diminished weight for age (<10th percentile) at 24 months
      (sensitivity=100%, 95% CI=(87, 100%)) than weight velocity (sensitivity=40%, 95%
      CI=(23, 59%)). Attained length at four months was more sensitive to detecting
      subsequent stunting (<10th percentile length for age) (77%, 95% CI=(62, 87%))
      than length velocity (30%, 95% CI=(19, 45%)). CONCLUSIONS: In CF infancy,
      attained weight or length is more sensitive than velocity-based definitions for
      predicting subsequent diminished growth.

PMID- 24917115
TI  - Adherence to clinical care guidelines for cystic fibrosis-related diabetes in 659
      German/Austrian patients.
AB  - BACKGROUND: In Germany/Austria, data on medical care for cystic fibrosis-related
      diabetes (CFRD) is limited. METHODS: Anonymized data from 659 CFRD patients were
      analyzed and compared to the latest ADA/CFF guidelines. RESULTS: Specialized
      diabetes clinics were attended less frequently than recommended (3.1 vs. 4.0
      times yearly). 7.9% of patients had a complete profile of examinations: diabetes
      education (44.9%), HbA1c (88.8%), blood pressure (79.5%), BMI (86.5%), lipid
      status (37.5%), retinopathy (29.9%), microalbuminuria (33.2%), and self
      monitoring of blood glucose (71.6%). HbA1c and blood pressure were measured less
      frequently than recommended (2.3 and 2.0 vs. 4.0 times yearly). Overall,
      guidelines were followed more frequently in children than adults. Contrary to
      recommendations, not all patients were treated with insulin (77.2 vs. 100.0%).
      Insulin therapy was initiated earlier in children than adults, but there was
      still a substantial delay (0.9 vs. 2.7years after diagnosis, p<0.001).
      CONCLUSION: In CFRD patients studied, adherence to care guidelines was
      suboptimal.

PMID- 24917116
TI  - Outcome in patients with cystic fibrosis liver disease.
AB  - BACKGROUND: Liver disease is an important complication in CF. AIMS: To determine
      if CFLD is a risk factor for mortality in CF, and which baseline characteristics
      predict all-cause mortality. METHODS: Irish children with CFLD, and their age and
      gender matched controls were enrolled at baseline and reviewed after 10years to
      determine which characteristics predict mortality. RESULTS: 72/84 (85.71%)
      participants were followed, (mean age Cases 21.71yrs SD 6.5, CF controls 23.62 SD
      5.6, 22 (61%) males), with no difference in duration of follow-up. Nineteen
      participants (26.4%) died, 38.9% (14/36) with CFLD and 13.89% (5/36) CF controls
      (Odds Ratio (OR) 3.94 95% CI:1.23-12.56 p=0.005). In logistic regression, liver
      disease (OR 4.28 95% CI 1.07-17.16) female gender (OR 12.25 95% CI 2.37-63.24),
      reduced pulmonary function, (OR 5.11 95% CI 1.09-23.81) were each independent
      risk factors for mortality in CF. CONCLUSIONS: Liver disease is an independent
      risk factor for mortality in CF.

PMID- 24917118
TI  - Peptide formation mechanism on montmorillonite under thermal conditions.
AB  - The oligomerization of amino acids is an essential process in the chemical
      evolution of proteins, which are precursors to life on Earth. Although some
      researchers have observed peptide formation on clay mineral surfaces, the
      mechanism of peptide bond formation on the clay mineral surface has not been
      clarified. In this study, the thermal behavior of glycine (Gly) adsorbed on
      montmorillonite was observed during heating experiments conducted at 150  degrees
      C for 336 h under dry, wet, and dry-wet conditions to clarify the mechanism.
      Approximately 13.9 % of the Gly monomers became peptides on montmorillonite under
      dry conditions, with diketopiperazine (cyclic dimer) being the main product. On
      the other hand, peptides were not synthesized in the absence of montmorillonite.
      Results of IR analysis showed that the Gly monomer was mainly adsorbed via
      hydrogen bonding between the positively charged amino groups and negatively
      charged surface sites (i.e., Lewis base sites) on the montmorillonite surface,
      indicating that the Lewis base site acts as a catalyst for peptide formation. In
      contrast, peptides were not detected on montmorillonite heated under wet
      conditions, since excess water shifted the equilibrium towards hydrolysis of the
      peptides. The presence of water is likely to control thermodynamic peptide
      production, and clay minerals, especially those with electrophilic defect sites,
      seem to act as a kinetic catalyst for the peptide formation reaction. 

PMID- 24917119
TI  - Efficacy of Grintuss(r) pediatric syrup in treating cough in children: a
      randomized, multicenter, double blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Cough is an extremely common problem in pediatrics, mostly triggered
      and perpetuated by inflammatory processes or mechanical irritation leading to
      viscous mucous production and increased sensitivity of the cough receptors.
      Protecting the mucosa might be very useful in limiting the contact with micro
      organisms and irritants thus decreasing the inflammation and mucus production.
      Natural molecular complexes can act as a mechanical barrier limiting cough
      stimuli with a non pharmacological approach but with an indirect anti
      inflammatory action. OBJECTIVE: Aim of the study was to assess the efficacy of a
      medical device containing natural functional components in the treatment of cough
      persisting more than 7 days. METHODS: In this randomized, parallel groups, double
      blind vs. placebo study, children with cough persisting more than 7 days were
      enrolled. The clinical efficacy of the study product was assessed evaluating
      changes in day- and night-time cough scores after 4 and 8 days (t4 and t8) of
      product administration. RESULTS: In the inter-group analysis, in the study
      product group compared with the placebo group, a significant difference (t4 study
      treatment vs. t4 placebo, p = 0.03) was observed at t4 in night-time cough
      score.Considering the intra-group analysis, only the study product group
      registered a significant improvement from t0 to t4 in both day-time (t0 vs. t4, p
      = 0.04) and night-time (t0 vs. t4, p = 0.003) cough scores.A significant
      difference, considering the study product, was also found in the following intra
      group analyses: day-time scores at t4 vs. t8 (p =0.01) and at t0 vs. t8 (p =
      0.001); night-time scores at t4 vs. t8 (p = 0.05), and at t0 vs. t8 (p = 0.005).
      Considering a subgroup of patients with higher cough (>= 3) scores, 92.9% of them
      in the study product group improved at t0 vs. t4 day-time. CONCLUSIONS:
      Grintuss(r) pediatric syrup showed to possess an interesting profile of efficacy
      and safety in the treatment of cough persisting more than 7 days.

PMID- 24917120
TI  - Structured RNAs and synteny regions in the pig genome.
AB  - BACKGROUND: Annotating mammalian genomes for noncoding RNAs (ncRNAs) is
      nontrivial since far from all ncRNAs are known and the computational models are
      resource demanding. Currently, the human genome holds the best mammalian ncRNA
      annotation, a result of numerous efforts by several groups. However, a more
      direct strategy is desired for the increasing number of sequenced mammalian
      genomes of which some, such as the pig, are relevant as disease models and
      production animals. RESULTS: We present a comprehensive annotation of structured
      RNAs in the pig genome. Combining sequence and structure similarity search as
      well as class specific methods, we obtained a conservative set with a total of
      3,391 structured RNA loci of which 1,011 and 2,314, respectively, hold strong
      sequence and structure similarity to structured RNAs in existing databases. The
      RNA loci cover 139 cis-regulatory element loci, 58 lncRNA loci, 11 conflicts of
      annotation, and 3,183 ncRNA genes. The ncRNA genes comprise 359 miRNAs, 8
      ribozymes, 185 rRNAs, 638 snoRNAs, 1,030 snRNAs, 810 tRNAs and 153 ncRNA genes
      not belonging to the here fore mentioned classes. When running the pipeline on a
      local shuffled version of the genome, we obtained no matches at the highest
      confidence level. Additional analysis of RNA-seq data from a pooled library from
      10 different pig tissues added another 165 miRNA loci, yielding an overall
      annotation of 3,556 structured RNA loci. This annotation represents our best
      effort at making an automated annotation. To further enhance the reliability, 571
      of the 3,556 structured RNAs were manually curated by methods depending on the
      RNA class while 1,581 were declared as pseudogenes. We further created a multiple
      alignment of pig against 20 representative vertebrates, from which RNAz predicted
      83,859 de novo RNA loci with conserved RNA structures. 528 of the RNAz
      predictions overlapped with the homology based annotation or novel miRNAs. We
      further present a substantial synteny analysis which includes 1,004 lineage
      specific de novo RNA loci and 4 ncRNA loci in the known annotation specific for
      Laurasiatheria (pig, cow, dolphin, horse, cat, dog, hedgehog). CONCLUSIONS: We
      have obtained one of the most comprehensive annotations for structured ncRNAs of
      a mammalian genome, which is likely to play central roles in both health
      modelling and production. The core annotation is available in Ensembl 70 and the
      complete annotation is available at
      http://rth.dk/resources/rnannotator/susscr102/version1.02.

PMID- 24917121
TI  - Irreversible inhibitors of the epidermal growth factor receptor: thienopyrimidine
      core with alpha,beta-unsaturated amide side chain.
AB  - Overexpression of epidermal growth factor receptor (EGFR) tyrosine kinases has
      been found in a variety of cancers such as breast, ovarian, colon, and non-small
      cell lung cancers, which is associated with poor prognosis in patients. In an
      effort to find effective irreversible inhibitors of the EGFR tyrosine kinase
      family (mainly HER2), two series of HER2 tyrosine kinase inhibitors with
      thieno[3,2-d]pyridine and thieno[2,3-d]pyridine as central part and with a basic
      alpha,beta-unsaturated amide side chain were developed. The alpha,beta
      unsaturated amide side chain (the Michael acceptor) at the 6-position, which
      forms a covalent bond to Cys773 located in the ATP binding pocket of the EGFR
      enzyme, is a major factor in the generation of irreversible inhibition. In our
      study, thienopyrimidine instead of quinazoline was used as the central structure,
      and different substituents were introduced at the 4-position to investigate the
      structure-activity relationships. The thieno[2,3-d]pyrimidine derivatives 16a-d
      showed potent HER2 enzyme inhibition and anti-proliferative activity against SK
      BR-3 cells. Especially, (E)-N-(4-((3-chloro-4-(pyridin-2
      ylmethoxy)phenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-4-(dimethylamino)but-2
      enamide 16d was identified as a potential irreversible HER2 inhibitor. Both its
      catalytic enzyme activity profile and its cellular efficacy were found to be
      superior to those of the marketed drug lapatinib. 

PMID- 24917122
TI  - Multiparametric magnetic resonance imaging outperforms the Prostate Cancer
      Prevention Trial risk calculator in predicting clinically significant prostate
      cancer.
AB  - BACKGROUND: The Prostate Cancer Prevention Trial risk calculator for high-grade
      (PCPTHG) prostate cancer (CaP) was developed to improve the detection of
      clinically significant CaP. In this study, the authors compared the performance
      of the PCPTHG against multiparametric magnetic resonance imaging (MP-MRI) in
      predicting men at risk of CaP. METHODS: Men with an abnormal prostate-specific
      antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion
      on a 3-Tesla MP-MRI were enrolled prospectively. Three radiologists reviewed and
      graded all lesions on a 5-point Likert scale. Biopsy of suspicious lesion(s) was
      performed using a proprietary MRI/transrectal ultrasound fusion-guided prostate
      biopsy system, after which 12-core biopsy was performed. A genitourinary
      pathologist reviewed all pathology slides. The performance of PCPTHG was compared
      with that of MP-MRI in predicting clinically significant CaP. RESULTS: Of 175 men
      who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP,
      including 93 of 113 men (82.3%) who had clinically significant disease. Age,
      abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI,
      apparent diffusion coefficient value, and MRI lesion size were identified as
      significant predictors of high-grade CaP (all P < .05). The area under the
      receiver operating characteristic curve of PCPTHG for predicting high-grade CaP
      was 0.676 (95% confidence interval [CI], 0.592-0.751). By using a risk cutoff of
      >=15% for biopsy as, proposed previously for high-grade CaP, sensitivity was
      96.4%, specificity was 7.6%, and the false-positive rate was 51.1%. In contrast,
      the area under the receiver operating characteristic curve of MP-MRI for high
      grade CaP was 0.769 (95% CI, 0.703-0.834), and it was 0.812 (95% CI, 0.754-0.869)
      for clinically significant CaP. CONCLUSIONS: MP-MRI outperforms PCPTHG in
      predicting clinically significant CaP, and its application may help select
      patients who will benefit from CaP diagnosis and treatment.

PMID- 24917123
TI  - Saudi Arabia reveals 113 previously undisclosed cases of Middle Eastern
      respiratory syndrome.

PMID- 24917124
TI  - Living environment matters: relationships between neighborhood characteristics
      and health of the residents in a Dutch municipality.
AB  - Characteristics of an individual alone cannot exhaustively explain all the causes
      of poor health, and neighborhood of residence have been suggested to be one of
      the factors that contribute to health. However, knowledge about aspects of the
      neighborhood that are most important to health is limited. The main objective of
      this study was to explore associations between certain features of neighborhood
      environment and self-rated health and depressive symptoms in Maastricht (The
      Netherlands). A large amount of routinely collected neighborhood data were
      aggregated by means of factor analysis to 18 characteristics of neighborhood
      social and physical environment. Associations between these characteristics and
      self-rated health and presence of depressive symptoms were further explored in
      multilevel logistic regression models adjusted for individual demographic and
      socio-economic factors. The study sample consisted of 9,879 residents (mean age
      55 years, 48 % male). Residents of unsafe communities were less likely to report
      good health (OR 0.88 95 % CI 0.80-0.97) and depressive symptoms (OR 0.81 95 % CI
      0.69-0.97), and less cohesive environment was related to worse self-rated health
      (OR 0.81 95 % CI 0.72-0.92). Residents of neighborhoods with more car traffic
      nuisance and more disturbance from railway noise reported worse mental health (OR
      0.79 95 % CI 0.68-0.92 and 0.85 95 % CI 0.73-0.99, respectively). We did not
      observe any association between health and quality of parking and shopping
      facilities, facilities for public or private transport, neighborhood aesthetics,
      green space, industrial nuisance, sewerage, neighbor nuisance or satisfaction
      with police performance. Our findings can be used to support development of
      integrated health policies targeting broader determinants of health. Improving
      safety, social cohesion and decreasing traffic nuisance in disadvantaged
      neighborhoods might be a promising way to improve the health of residents and
      reduce health inequalities.

PMID- 24917125
TI  - Pyrosequencing analysis yields comprehensive assessment of microbial communities
      in pilot-scale two-stage membrane biofilm reactors.
AB  - We studied the microbial community structure of pilot two-stage membrane biofilm
      reactors (MBfRs) designed to reduce nitrate (NO3(-)) and perchlorate (ClO4(-)) in
      contaminated groundwater. The groundwater also contained oxygen (O2) and sulfate
      (SO4(2-)), which became important electron sinks that affected the NO3(-) and
      ClO4(-) removal rates. Using pyrosequencing, we elucidated how important
      phylotypes of each "primary" microbial group, i.e., denitrifying bacteria (DB),
      perchlorate-reducing bacteria (PRB), and sulfate-reducing bacteria (SRB),
      responded to changes in electron-acceptor loading. UniFrac, principal coordinate
      analysis (PCoA), and diversity analyses documented that the microbial community
      of biofilms sampled when the MBfRs had a high acceptor loading were
      phylogenetically distant from and less diverse than the microbial community of
      biofilm samples with lower acceptor loadings. Diminished acceptor loading led to
      SO4(2-) reduction in the lag MBfR, which allowed Desulfovibrionales (an SRB) and
      Thiothrichales (sulfur-oxidizers) to thrive through S cycling. As a result of
      this cooperative relationship, they competed effectively with DB/PRB phylotypes
      such as Xanthomonadales and Rhodobacterales. Thus, pyrosequencing illustrated
      that while DB, PRB, and SRB responded predictably to changes in acceptor loading,
      a decrease in total acceptor loading led to important shifts within the "primary"
      groups, the onset of other members (e.g., Thiothrichales), and overall greater
      diversity. 

PMID- 24917126
TI  - Do postliver transplant patients need thromboprophylactic anticoagulation?
AB  - Postoperative thromboprophylactic anticoagulation against Deep Vein Thrombosis
      (DVT) and Pulmonary Embolism (PE) is standard of care with current evidence-based
      guidelines. However, majority of liver transplant (LT) patients have
      thrombocytopenia and/or prolonged INR before surgery. Studies or guidelines
      regarding role of prophylactic anticoagulation after LT are lacking. There is a
      need to balance the risk of thrombosis with significant hemorrhage, implying
      those needing transfusion or return to OR due to bleeding. We conclude that after
      LT, anticoagulation is not required routinely for DVT/PE prophylaxis. Rather, it
      is indicated in specific circumstances, chiefly for prophylaxis of hepatic artery
      thrombosis or portal vein thrombosis in cases with use of grafts, pediatric
      cases, small size vessels, Budd Chiari syndrome, amongst others. 

PMID- 24917127
TI  - Embolisation for caecal bleeding in a child with typhlitis.
AB  - A 16-year-old girl being treated for a relapse of promyelocytic leukaemia
      developed typhlitis of the caecum and ascending colon related to Klebsiella
      septicaemia during the neutropenic phase, 2 weeks after the start of induction
      treatment with chemotherapy. After 10 days of treatment with parenteral feeding
      and antibiotics, massive rectal blood loss occurred, causing haemodynamic
      instability. Contrast-enhanced abdominal CT showed contrast extravasation in the
      caecal lumen. This life-threatening situation prompted visceral angiography,
      which confirmed a contrast blush in the caecum. Subsequent embolisation resulted
      in haemodynamic stability.

PMID- 24917128
TI  - The role of exclusive breastfeeding and sugar-sweetened beverage consumption on
      preschool children's weight gain.
AB  - BACKGROUND: Sugar-sweetened beverages (SSBs) and breastfeeding practices have
      been recognized as important factors linked to children's weight status. However,
      no other studies have simultaneously investigated the role of each factor on
      children's conditional weight gain (CWG). OBJECTIVE: To evaluate the role of
      exclusive breastfeeding (EB) and the SSBs consumption on CWG from birth to the
      survey date among Brazilian preschool children (24-59 months old). METHODS: A
      nationally represented cross-sectional survey with complex probability sampling
      (n = 2421) was conducted. The outcome variable - CWG - represents how much an
      individual has deviated from its expected weight gain, given his or her prior
      weight. The multivariate linear regression to analyse the effects of EB and the
      consumption of SSBs on CWG were adjusted for economic status and maternal
      variables. RESULTS: There was a significantly protective effect of EB duration
      during the first year of life on CWG from birth to the survey date (-0.02 [-0.03;
      0.00 95% confidence interval]); however, the SSBs intake promoted an effect on
      the weight gain that was 2.5-fold higher (0.05 [0.02; 0.08 95% confidence
      interval]) than the EB. CONCLUSION: As hypothesized, the exposure variables acted
      in opposite directions, but the harmful effect of SSBs intake had greater
      magnitude than the beneficial effect of EB on children's CWG.

PMID- 24917129
TI  - Identification of novel mutations in the VPS33B gene involved in arthrogryposis,
      renal dysfunction, and cholestasis syndrome.
AB  - Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal
      recessive disorder caused by mutations in the VPS33B and VIPAS39. Here, we report
      novel mutations identified in four patients with ARC syndrome. We analyzed the
      entire coding regions of the VPS33B and VIPAS39 genes by direct sequencing. To
      detect novel splice site mutations, mRNA transcripts were analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR) and sequencing. All four
      patients had compound heterozygous variants in the VPS33B gene. One patient had a
      previously reported splice site variant with unknown significance, c.239+5G>A,
      and a novel nonsense mutation, c.621G>A. The other three patients had the
      c.403+2T>A mutation, and each of them carried one of the splice site variants,
      c.239+5G>A or c.499-11G>A. c.239+5G>A and c.499-11G>A created novel splice sites
      which resulted in abnormal transcripts. No significant VIPAS39 mutation was
      detected in all patients. In patients suspected with ARC syndrome, mutation
      analysis of the VPS33B gene should be employed as a primary diagnostic test
      before performing invasive testing procedures such as organ biopsies. Performing
      mRNA analysis can be useful in predicting the pathogenic phenotype when the
      mutation seems to affect a normal splicing mechanism. 

PMID- 24917130
TI  - Mapping-by-sequencing accelerates forward genetics in barley.
AB  - Mapping-by-sequencing has emerged as a powerful technique for genetic mapping in
      several plant and animal species. As this resequencing-based method requires a
      reference genome, its application to complex plant genomes with incomplete and
      fragmented sequence resources remains challenging. We perform exome sequencing of
      phenotypic bulks of a mapping population of barley segregating for a mutant
      phenotype that increases the rate of leaf initiation. Read depth analysis
      identifies a candidate gene, which is confirmed by the analysis of independent
      mutant alleles. Our method illustrates how the genomic resources of barley
      together with exome resequencing can underpin mapping-by-sequencing. 

PMID- 24917131
TI  - Crystalglobulinemia syndrome due to monoclonal gammopathy of renal significance.

PMID- 24917132
TI  - Peptide YY: more than just an appetite regulator.
AB  - Replenishment of beta cell mass is a key aim of novel therapeutic interventions
      for diabetes, and the implementation of new strategies will be aided by
      understanding the mechanisms employed to regulate beta cell mass under normal
      physiological conditions. We have recently identified a new role for the gut
      hormone peptide YY (PYY) and the neuropeptide Y (NPY) receptor systems in the
      control of beta cell survival. PYY is perhaps best known for its role in
      regulating appetite and body weight, but its production by islet cells, the
      presence of NPY receptors on islets and the demonstration that Y1 activation
      causes proliferation of beta cells and protects them from apoptosis, suggest a
      role for this peptide in modulating beta cell mass. This review introduces PYY
      and its potential role in glucose homeostasis, then focuses on evidence
      supporting the concept that PYY and NPY receptors are exciting new targets for
      the preservation of beta cells. 

PMID- 24917133
TI  - Effects of sacral neuromodulation on isolated urinary bladder function in a rat
      model of spinal cord injury.
AB  - INTRODUCTION: Sacral neuromodulation has been considered as an effective
      treatment option for various types of chronic voiding dysfunction, but the
      mechanism of action has not been well understood. The aim of this study was to
      evaluate the effect of chronic sacral neuromodulation on isolated bladder
      functions in a rat model of spinal cord injury. MATERIALS AND METHODS: Female
      Sprague-Dawley rats (250-300 g; N = 20) were assigned to four groups as follows:
      1) control group (N = 6); 2) spinal cord transection group (SCT; N = 5); 3)
      spinal cord transection + sacral neuromodulation group (SCT + SNM; N = 5); 4)
      sham (spinal cord transection + electrode wire implantation without sacral
      neuromodulation; N = 4). The rats in the SCT, SCT + SNM, and sham groups were
      anesthetized with ketamine (60 mg/kg, i.p.) and xylazine (7 mg/kg, i.p.). The
      spinal cord was completely transected at T8-T9 level in SCT and SCT + SNM groups.
      Electrode wires were implanted into S3 dorsal foramina in both sham and SNM
      groups, but only the SNM group was subjected to electrical stimulation for four
      hours a day for three weeks. Twenty-one days later, the rats were sacrificed via
      anesthetic overdose, and isolated longitudinal bladder strip preparations were
      placed in organ baths for the investigation of their isometric responses to
      pharmacological agents. RESULTS: In isometric contraction experiments, SCT was
      found to increase the contraction responses of the bladder strips to muscarinic
      stimulation, and SNM could not prevent this increase. In isometric relaxation
      experiments, SCT caused a decrease in beta-adrenergic relaxation responses, and
      SNM augmented the bladder's beta-adrenergic relaxation responses. Nitric oxide
      did not affect the relaxation responses. CONCLUSION: In our rat model of SCT, SNM
      seemed to alter adrenergic receptor function in the urinary bladder. Further
      studies are required to clarify the mechanism of these alterations at the level
      of bladder receptors following sacral neuromodulation.

PMID- 24917134
TI  - The ecology of the planktonic diatom Cyclotella and its implications for global
      environmental change studies.
AB  - The fossil record of diatoms in lake sediments can be used to assess the effects
      of climate variability on lake ecosystems if ecological relationships between
      diatom community structure and environmental parameters are well understood.
      Cyclotella sensu lato taxa are a key group of diatoms that are frequently
      dominant members of phytoplankton communities in low- to moderate-productivity
      lakes. Their relative abundances have fluctuated significantly in
      palaeolimnological records spanning over a century in arctic, alpine, boreal and
      temperate lakes. This suggests that these species are sensitive to environmental
      change and may serve as early indicators of ecosystem effects of global change.
      Yet patterns of change in Cyclotella species are not synchronous or
      unidirectional across, or even within, regions, raising the question of how to
      interpret these widespread changes in diatom community structure. We suggest that
      the path forward in resolving seemingly disparate records is to identify clearly
      the autecology of Cyclotella species, notably the role of nutrients, dissolved
      organic carbon and light, coupled with better consideration of both the
      mechanisms controlling lake thermal stratification processes and the resulting
      effects of changing lake thermal regimes on light and nutrients. Here we begin by
      reviewing the literature on the resource requirements of common Cyclotella taxa,
      illustrating that many studies reveal the importance of light, nitrogen,
      phosphorus, and interactions among these resources in controlling relative
      abundances. We then discuss how these resource requirements can be linked to
      shifts in limnological processes driven by environmental change, including
      climate-driven change in lakewater temperature, thermal stratification and
      nutrient loading, as well as acidification-driven shifts in nutrients and water
      clarity. We examine three case studies, each involving two lakes from the same
      region that have disparate trends in the relative abundances of the same species,
      and illustrate how the mechanisms by which these species abundances are changing
      can be deciphered. Ultimately, changes in resource availability and water clarity
      are key factors leading to shifts in Cyclotella abundances. Tighter integration
      of the autecology of this important group of diatoms with environmental change
      and subsequent alterations in limnological processes will improve interpretations
      of palaeolimnological records, and clarify the drivers of seemingly disparate
      patterns in fossil records showing widespread and rapid changes across the
      northern hemisphere. 

PMID- 24917136
TI  - Intrastromal application of riboflavin for corneal crosslinking.
AB  - PURPOSE: To experimentally evaluate the efficacy of corneal crosslinking (CXL) by
      injecting the photomediator riboflavin into the corneal stroma via intrastromal
      channels. METHODS: Five groups of pig corneas, nine each, were compared regarding
      stress-strain relationship and UV-absorption. Group 1 had intrastromal channels
      floated with riboflavin 0.5%-solution followed by UVA-irradiation (3 mW/cm(2) for
      30 minutes); group 2 was handled like group 1, but were irradiated with 9
      mW/cm(2) for 10 minutes; group 3 was treated according to the Dresden protocol
      (epi-off, 9 mW/cm(2) for 10 minutes); group 4 had the identical channel system,
      no riboflavin but identical irradiation; group 5 with native corneas served as a
      control group. The intrastromal channels were created with a femtosecond laser.
      The stress-strain relations were measured in corneal strips using a uniaxial
      material tester at strains up to 12%. The UV-transmission of the corneas was
      measured in groups 1, 3, and 5. RESULTS: The stress needed for a 10% strain was
      significantly increased by 82% in the corneas treated with the Dresden protocol
      compared with native cornea (P = 0.0005). With intrastromal application of
      riboflavin the significant increase was 87% (P = 0.0005) in group 1 and 64% (P =
      0.007) in group 2. The channel formation alone did not alter biomechanics (P =
      0.923). The corneal UVA-transmission was 2.4% after intrastromal riboflavin
      application, 8.9% after the treatment according to the Dresden protocol, and
      57.9% in native corneas. CONCLUSIONS: The experiments demonstrate the
      intrastromal application of riboflavin by means of intrastromal channels a
      feasible "epi-on" approach for CXL. More experimental data are needed before
      clinical testing.

PMID- 24917135
TI  - Mitigation of oxygen-induced retinopathy in alpha2beta1 integrin-deficient mice.
AB  - PURPOSE: The alpha2beta1 integrin plays an important but complex role in
      angiogenesis and vasculopathies. Published GWAS studies established a correlation
      between genetic polymorphisms of the alpha2beta1 integrin gene and incidence of
      diabetic retinopathy. Recent studies indicated that alpha2-null mice demonstrate
      superior vascularization in both the wound and diabetic microenvironments. The
      goal of this study was to determine whether the vasculoprotective effects of
      alpha2-integrin deficiency extended to the retina, using the oxygen-induced
      retinopathy (OIR) model for retinopathy of prematurity (ROP). METHODS: In the OIR
      model, wild-type (WT) and alpha2-null mice were exposed to 75% oxygen for 5 days
      (postnatal day [P] 7 to P12) and subsequently returned to room air for 6 days
      (P12-P18). Retinas were collected at postnatal day 7, day 13, and day 18 and
      examined via hematoxylin and eosin and Lectin staining. Retinas were analyzed for
      retinal vascular area, neovascularization, VEGF expression, and Muller cell
      activation. Primary Muller cell cultures from WT and alpha2-null mice were
      isolated and analyzed for hypoxia-induced VEGF-A expression. RESULTS: In the
      retina, the alpha2beta1 integrin was minimally expressed in endothelial cells and
      strongly expressed in activated Muller cells. Isolated alpha2-null primary Muller
      cells demonstrated decreased hypoxia-induced VEGF-A expression. In the OIR model,
      alpha2-null mice displayed reduced hyperoxia-induced vaso-attenuation, reduced
      pathological retinal neovascularization, and decreased VEGF expression as
      compared to WT counterparts. CONCLUSIONS: Our data suggest that the alpha2beta1
      integrin contributes to the pathogenesis of retinopathy. We describe a newly
      identified role for alpha2beta1 integrin in mediating hypoxia-induced Muller cell
      VEGF-A production.

PMID- 24917138
TI  - Cyclic stretch and hypertension increase retinal succinate: potential mechanisms
      for exacerbation of ocular neovascularization by mechanical stress.
AB  - PURPOSE: We investigated succinate metabolism in cells undergoing clinically
      relevant cyclic stretch and in spontaneously hypertensive rat (SHR) retina.
      METHODS: We seeded ARPE-19 cells on 6-well BioFlex collagen I-coated, silicone
      elastomer-bottomed culture plates. Cells then were subjected to pulsatile stretch
      using a computer-controlled vacuum stretch apparatus. A physiologic stretch
      frequency of 60 cycles per minute and 5% to 15% prolongation of the elastomer
      bottomed plates were used. Succinate concentration was assessed by enzymatic
      analysis and high-performance liquid chromatography-mass spectrometry. The VEGF
      was measured using enzyme-linked immunosorbent assays. The 12-week-old male SHRs
      and weight-matched Wistar-Kyoto (WKY) control rats were treated with or without
      100 mg.kg(-1).day(-1) captopril for 1 week. The vitreous body and retina of each
      rat were extracted after 1 week of therapy, and the vitreoretinal succinate
      concentration was measured. RESULTS: Cells exposed to cyclic stretch accumulated
      intracellular succinate in a time- and magnitude-dependent manner, and also
      accumulated VEGF protein levels. Moreover, BAPTA/AM, an intracellular calcium
      chelate reagent, significantly inhibited the stretch-induced succinate increase.
      After cyclic stretch, levels of intracellular fumarate, a citric acid cycle
      intermediate, also were significantly increased compared to controls. The
      BAPTA/AM inhibited this increase. For the in vivo experiments, hypertension
      increased vitreoretinal succinate and fumarate in SHRs compared to the
      normotensive WKY controls. When hypertension was reduced using captopril,
      vitreoretinal succinate returned to baseline levels. CONCLUSIONS: These findings
      suggest that cyclic stretch and hypertension increased intracellular succinate in
      cultured retinal pigment epithelial cells and the vitreoretinal succinate of SHRs
      through a calcium-dependent pathway.

PMID- 24917137
TI  - RNA expression analysis of passive transfer myasthenia supports extraocular
      muscle as a unique immunological environment.
AB  - PURPOSE: Myasthenia gravis demonstrates a distinct predilection for involvement
      of the extraocular muscles (EOM), and we have hypothesized that this may be due
      to a unique immunological environment. To assess this hypothesis, we took an
      unbiased approach to analyze RNA expression profiles in EOM, diaphragm, and
      extensor digitorum longus (EDL) in rats with experimentally acquired myasthenia
      gravis (EAMG). METHODS: Experimentally acquired myasthenia gravis was induced in
      rats by intraperitoneal injection of antibody directed against the acetylcholine
      receptor (AChR), whereas control rats received antibody known to bind the AChR
      but not induce disease. After 48 hours, animals were killed and muscles analyzed
      by RNA expression profiling. Profiling results were validated using qPCR and
      immunohistochemical analysis. RESULTS: Sixty-two genes common among all muscle
      groups were increased in expression. These fell into four major categories: 12.8%
      stress response, 10.5% immune response, 10.5% metabolism, and 9.0% transcription
      factors. EOM expressed 212 genes at higher levels, not shared by the other two
      muscles, and a preponderance of EOM gene changes fell into the immune response
      category. EOM had the most uniquely reduced genes (126) compared with diaphragm
      (26) and EDL (50). Only 18 downregulated genes were shared by the three muscles.
      Histological evaluation and disease load index (sum of fold changes for all
      genes) demonstrated that EOM had the greatest degree of pathology. CONCLUSIONS:
      Our studies demonstrated that consistent with human myasthenia gravis, EOM
      demonstrates a distinct RNA expression signature from EDL and diaphragm, which is
      based on differences in the degree of muscle injury and inflammatory response.

PMID- 24917139
TI  - Translation, cultural adaptation, and Rasch analysis of the visual function (VF
      14) questionnaire.
AB  - PURPOSE: To translate, culturally adapt, and validate the original and previously
      validated shorter versions of the Visual Function Index (VF-14) questionnaire in
      a Chinese population. METHODS: The VF-14 was completed by patients with cataract.
      The analysis was carried out in three phases: phase I, testing whether the VF-14
      and its valid shorter versions,VF-8R and VF-11R, form valid scales in Chinese
      settings using Rasch analysis; phase II, developing completely new Chinese
      versions of the VF-14; phase III, testing whether the previously validated
      shorter versions of the VF-14 could be applied in a Chinese population. This was
      tested by assessing the agreement between the new Chinese (developed in phase II)
      and the previously validated shorter versions of the VF-14 using Bland-Altman
      plots. RESULTS: A total of 456 patients (median age, 70 years; range, 40-92
      years; females, 58%) completed the Chinese translated version of the VF-14. The
      VF-14 and the VF-11R demonstrated good Rasch based psychometric properties when a
      grossly misfitting item was removed. The VF-8R formed a valid scale without any
      modification. The scores of the VF-11R and the Chinese shorter version (VF
      11RChin) showed very good agreement, with a mean difference of -0.18 logits and
      95% limits of agreement between 0.11 and -0.47. CONCLUSIONS: The Chinese
      translated VF-14, VF-11R, and VF-8R were valid and could be applied to assess
      cataract outcomes in Chinese settings. The existing shorter version had good
      agreement with the new Chinese version, which signifies that there was no need to
      develop a different version of the VF-14 in China.

PMID- 24917140
TI  - Longitudinal study of iris concavity, corneal biomechanics, and correlations to
      ocular biometry in a cohort of 10- to 12-year-old UK schoolboys: 2-year follow-up
      data.
AB  - PURPOSE: To explore changes in iris curvature over a 2-year period. To
      investigate associations between iris curvature and ocular biometric parameters.
      To explore relationships between a number of nonocular measurements and ocular
      biometric parameters. METHODS: Schoolboys enrolled 2 years previously were
      invited to return for anterior segment optical coherence tomography, corneal
      hysteresis (CH), corneal resistance factor (CRF), and axial biometric
      measurements. Refractive error was assessed and measures of height, weight, waist
      circumference, digit ratio, and percentage body fat taken. RESULTS: Mean
      spherical equivalent refraction reduced by 0.76 diopters and mean iris concavity,
      defined as a measurement of less than or equal to -0.1 mm, increased by 0.018 mm
      at distance fixation and 0.04 mm on accommodation. Compared with 2 years
      previously, the prevalence of iris concavity increased from 24% to 32% on
      distance fixation and from 65% to 84% on accommodation. Variables significantly
      associated with nonaccommodating iris curvature were anterior chamber depth (ACD,
      P = 0.029) and mean scleral spur angle (P = 0.0001). Variables significantly
      associated with accommodating iris curvature were ACD (P = 0.02), lens vault (P =
      0.047), and scleral spur angle (P < 0.0001). Significant association was again
      found between CH and accommodating spur-to-spur distance (R(2) = 0.13, P =
      0.007). CONCLUSIONS: Iris concavity was more prevalent in this cohort of
      schoolboys than 2 years earlier. The degree of concavity remains related to ACD
      and lens vault. The association between spur-to-spur distance and CH was similar
      at baseline and after 2 years.

PMID- 24917141
TI  - Association of LOXL1 polymorphisms with pseudoexfoliation, glaucoma, intraocular
      pressure, and systemic diseases in a Greek population. The Thessaloniki eye
      study.
AB  - PURPOSE: To investigate the association of the two single-nucleotide
      polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene with
      pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary
      open-angle glaucoma (POAG) in a Greek population-based setting, from the
      Thessaloniki Eye study. METHODS: A total of 233 subjects with successful DNA
      extraction, PCR amplification, and genotyping were included in the genetic
      analysis of G153D and R141L SNPs of LOXL1 gene and classified into four groups:
      controls (n = 93); subjects with PEX (n = 40); POAG (n = 66); and PEXG (n = 34).
      Multinomial logistic regression was used to test their association with LOXL1
      SNPs with adjustment for covariates. The association of LOXL1 with IOP (in
      untreated subjects) and with systemic diseases was explored. RESULTS: Both LOXL1
      SNPs were present in high frequencies in controls and cases. The G153D was
      strongly associated with both PEX (odds ratio [OR] = 23.2, P = 0.003 for allele
      G) and PEXG (OR = 24.75, P = 0.003 for allele G) and was not associated with POAG
      (P = 0.451). In contrast, the R141L was not associated with PEX (P = 0.81), PEXG
      (P = 0.063), or POAG (P = 0.113). No association of the G153D with either
      intraocular pressure (IOP) or systemic diseases was found. CONCLUSIONS: In the
      Thessaloniki Eye Study, the G153D SNP of LOXL1 gene was strongly associated with
      both PEX and PEXG, whereas the R141L was not associated. No association of the
      LOXL1 with IOP or with systemic diseases was found. These findings further
      support the hypothesis that the LOXL1 gene contributes to onset of PEXG through
      PEX. Gene variants of LOXL1 do not help to identify those with PEX at increased
      risk for glaucoma development.

PMID- 24917143
TI  - Retinal topography of myopic eyes: a spectral-domain optical coherence tomography
      study.
AB  - PURPOSE: The purpose of this study was to investigate topographic characteristics
      of the retina in myopic eyes. METHODS: We reviewed spectral-domain optical
      coherence tomography (SD-OCT) images of patients with myopia retrospectively.
      Retinal topography (RT) was defined as the topography of the retinal pigment
      epithelium layers. Retinal topographies were classified into several types, and
      the distribution and characteristics of each type were assessed in eyes with
      varying degrees of axial length (AL). RESULTS: A total of 167 subjects with
      myopia were included in this study. Seventy eyes (41.9%) were classified as
      regular (R) type, 48 (28.7%) were wave (W) type, 32 (19.2%) were band (B) type,
      and 17 (10.2%) were pond (P) type. The distribution of these types varied
      significantly among eyes with different degrees of AL (P < 0.001); R-type was
      predominant in eyes with 24 mm less than or equal to AL less than 26 mm, and P
      type in eyes with AL greater than or equal to 28 mm. The retina sloped away from
      the cornea more frequently on the nasal side than it did on the temporal side or
      in between the nasal and the temporal sides, with the exception of the P-type RT.
      Topography of the central zone was frequently slanted, except in B-type eyes. The
      difference between the refractive and corneal astigmatism of eyes with P-type RT
      was greater than that of B-type eyes (P = 0.002). CONCLUSIONS: Retinal topography
      varies according to the degree of AL. This variation in RT may originate from the
      differences between healthy eyes and highly myopic eyes, and may be related to
      the optical characteristics of the eye.

PMID- 24917142
TI  - The role of cytochrome P450 epoxygenases in retinal angiogenesis.
AB  - PURPOSE: The purpose of this study was to investigate the role(s) of cytochrome
      P450 epoxygenases (CYPs) and their products, the epoxyeicosatrienoic acids
      (EETs), in hypoxia-induced VEGF production and pathologic retinal angiogenesis.
      METHODS: Human retinal astrocytes, Muller cells, and retinal microvascular
      endothelial cells (HRMEC) were exposed to hypoxia, and relative CYP2C expression
      was measured by RT-PCR. Astrocyte and Muller cell VEGF production was measured by
      ELISA after exposure to hypoxia and treatment with the general CYP inhibitor, SKF
      525a. Human retinal microvascular endothelial cells were treated with the CYP
      product, 11,12-epoxyeicosatrienoic acid [EET], or SKF-525a in the presence or
      absence of VEGF. Proliferation of HRMEC and tube formation were assayed. Oxygen
      induced retinopathy (OIR) was induced in newborn rats. Retinal CYP2C11 and
      CYP2C23 expression were measured by RT-PCR. The OIR rats received SKF-525a by
      intravitreal injection and preretinal neovascularization (NV) was quantified.
      Retinal VEGF protein levels were measured by ELISA. RESULTS: Human retinal
      astrocytes were the only cells to exhibit significant induction of CYP2C8 and
      CYP2C9 mRNA expression by hypoxia. Astrocytes, but not Muller cells, exhibited
      reduced hypoxia-induced VEGF production when treated with SKF-525a. 11,12-EET
      induced HRMEC proliferation and tube formation, and SKF-525a inhibited VEGF
      induced proliferation. Oxygen-induced retinopathy induced expression of CYP2C23,
      but had no effect on CYP2C11. SKF-525a inhibited retinal NV and reduced retinal
      VEGF levels in OIR rats. CONCLUSIONS: The CYP-derived 11,12-EET may exhibit a
      proangiogenic biological function in the retina following stimulation by hypoxia
      in astrocytes. Inhibition of CYP may provide a rational therapy against retinal
      NV, because it can reduce VEGF production and VEGF-induced angiogenic responses
      in endothelial cells.

PMID- 24917145
TI  - Angiopoietin-1 is regulated by miR-204 and contributes to corneal
      neovascularization in KLEIP-deficient mice.
AB  - PURPOSE: Corneal neovascularization can cause loss of vision. The introduction of
      anti-VEGF therapy has been a major improvement in therapeutic options. Recently,
      we established Kelch-like Ect2-interacting protein (KLEIP/KLHL20) knockout mice
      as a model of spontaneous corneal neovascular dystrophy. The aim of the present
      study was to characterize corneal neovascularization in progressive corneal
      dystrophy in KLEIP(-/-) mice, to evaluate the efficacy of anti-VEGF therapy, and
      to identify novel molecular regulators in this experimental model. METHODS:
      Corneal neovascularization was assessed by immunohistochemistry. Vascular
      endothelial growth factor signaling was inhibited by injection of a blocking
      antibody. Microarrays were used to measure expression of mRNA and microRNA
      (miRNA) in dystrophic corneae. Results were validated by immunohistochemistry and
      Western blotting. RESULTS: Blood vessels and lymphatics grew from the limbus
      toward the dystrophic epithelium in corneae of KLEIP(-/-) mice. Blocking VEGF
      signaling did not reduce phenotype progression. Correspondingly, microarray
      analysis revealed no upregulation of canonical vascular growth factors in late
      dystrophy. During phenotype progression, angiopoietin-1 expression increased
      while miR-204 expression decreased. Bioinformatic analysis identified a binding
      site for miR-204 in the angiopoietin-1 gene. Validation by in vitro experiments
      confirmed regulation of angiopoietin-1 by miR-204. CONCLUSIONS: Vascular
      endothelial growth factor does not act as a major player in corneal
      neovascularization in KLEIP(-/-) mice. However, the proangiogenic factor
      angiopoietin-1 was strongly upregulated in late-stage phenotype, correlating with
      loss of miR-204 expression. Correspondingly, we identified miR-204 as a novel
      regulator of angiopoietin-1 in vitro. These findings may explain the incomplete
      efficacy of anti-VEGF therapy in the clinic and may provide new candidates for
      pharmaceutical intervention.

PMID- 24917146
TI  - NF-kappaB mediates the survival of corneal myofibroblast induced by angiotensin
      II.
AB  - PURPOSE: To investigate the role of angiotensin II (Ang II) in the regulation of
      corneal myofibroblast apoptosis and the possible signaling pathway. METHODS:
      Rabbit corneal myofibroblasts were cultured in vitro and the cell phenotype was
      identified by expression of alpha-smooth muscle actin (alpha-SMA) and formation
      of F-actin. The expression of Ang II type I receptor (AT1R) in keratocytes and
      corneal myofibroblasts were detected by immunofluorescence staining and Western
      blot. The effect of Ang II on corneal myofibroblast apoptosis induced by serum
      starvation and TNFalpha plus cycloheximide (CHX) was examined by TUNEL, Hoechst
      33258 staining, and caspase 3/7 activity assay. The effect of Ang II on nuclear
      factor-kappaB (NF-kappaB)-dependent DNA binding activity and transcriptional
      activity was studied by electrophoresis mobility shift assay (EMSA) and
      luciferase reporter assay, respectively. Ang II-induced TGFbeta1 secretion by
      corneal myofibroblasts was determined by ELISA. RESULTS: Ang II type I receptor
      expression was more abundant in corneal myofibroblasts compared with keratocytes.
      Ang II reduced corneal myofibroblasts apoptotic response to serum starvation or
      treatment with TNFalpha plus CHX. This protective effect was attenuated in the
      presence of AT1R antagonist losartan or NF-kappaB-specific inhibitor Bay11-7082.
      Ang II increased NF-kappaB-dependent DNA-binding activity and transcriptional
      activity, and also increased TGFbeta1 production by corneal myofibroblasts.
      CONCLUSIONS: Ang II induces corneal myofibroblasts resistance to apoptosis via
      activating NF-kappaB signaling pathway, and thus should be further investigated
      as a possible target for therapy of corneal fibrosis.

PMID- 24917144
TI  - Mitochondrial polymorphism A10398G and Haplogroup I are associated with Fuchs'
      endothelial corneal dystrophy.
AB  - PURPOSE: We investigated whether mitochondrial DNA (mtDNA) variants affect the
      susceptibility of Fuchs endothelial corneal dystrophy (FECD). METHODS: Ten mtDNA
      variants defining European haplogroups were genotyped in a discovery dataset
      consisting of 530 cases and 498 controls of European descent from the Duke FECD
      cohort. Association tests for mtDNA markers and haplogroups were performed using
      logistic regression models with adjustment of age and sex. Subset analyses
      included controlling for additional effects of either the TCF4 SNP rs613872 or
      cigarette smoking. Our replication dataset was derived from the genome-wide
      association study (GWAS) of the FECD Genetics Consortium, where genotypes for
      three of 10 mtDNA markers were available. Replication analyses were performed to
      compare non-Duke cases to all GWAS controls (GWAS1, N = 3200), and to non-Duke
      controls (GWAS2, N = 3043). RESULTS: The variant A10398G was significantly
      associated with FECD (odds ratio [OR] = 0.72; 95% confidence interval [CI] =
      [0.53, 0.98]; P = 0.034), and remains significant after adjusting for smoking
      status (min P = 0.012). This variant was replicated in GWAS1 (P = 0.019) and
      GWAS2 (P = 0.036). Haplogroup I was significantly associated with FECD (OR =
      0.46; 95% CI = [0.22, 0.97]; P = 0.041) and remains significant after adjusting
      for the effect of smoking (min P = 0.008) or rs613872 (P = 0.034). CONCLUSIONS:
      The 10398G allele and Haplogroup I appear to confer significant protective
      effects for FECD. The effect of A10398G and Haplogroup I to FECD is likely
      independent of the known TCF4 variant. More data are needed to decipher the
      interaction between smoking and mtDNA haplogroups.

PMID- 24917147
TI  - Rates of glaucomatous visual field change in a large clinical population.
AB  - PURPOSE: To determine the rate of glaucomatous visual field change in routine
      clinical care. METHODS: Mean deviation (MD) rate was computed in one randomly
      selected eye of all glaucoma patients and suspects with >=5 examinations in a
      tertiary eye-care center. Proportions of "fast" (MD rate, <-1 to -2 dB/y) and
      "catastrophic" (<-2 dB/y) progressors were determined. The MD rates were computed
      in tertile groups by the number of examinations, baseline age, and MD. The MD
      rates were compared to the Canadian Glaucoma Study (CGS), a prospective study
      with IOP interventions mandated by visual field progression, by pairwise matching
      of patients by baseline MD. RESULTS: There were 2324 patients with median
      (interquartile range) baseline age and MD of 65 (56, 74) years and -2.44 (-5.44, 
      0.86) dB, and follow-up of 7.1 (4.8, 10.2) years with 8 (6, 11) examinations. The
      median MD rate was -0.05 (0.13, -0.30) dB/y, while the mean follow-up IOP was
      17.1 (15.0, 19.7) mm Hg. The MD rate was progressively worse, with a doubling of
      fast and catastrophic progressors, with each tertile of increasing age. Worse MD
      rate was associated with lower follow-up IOP. Neither MD rate nor the number of
      fast and catastrophic progressors was significantly different in clinical care
      patients matched to CGS patients. CONCLUSIONS: Most patients under routine
      glaucoma care demonstrate slow rates of visual field progression. The MD rate in
      the current study was similar to an interventional prospective study, but
      considerably less negative compared to published studies with similar design.

PMID- 24917148
TI  - Evaluation of protein supplementation for growing cattle fed grass silage-based
      diets: a meta-analysis.
AB  - The objective of this meta-analysis was to develop empirical equations predicting
      growth responses of growing cattle to protein intake. Overall, the data set
      comprised 199 diets in 80 studies. The diets were mainly based on grass silage or
      grass silage partly or completely replaced by whole-crop silages or straw. The
      concentrate feeds consisted of cereal grains, fibrous by-products and protein
      supplements. The analyses were conducted both comprehensively for all studies and
      also separately for studies in which soybean meal (SBM; n=71 diets/28 studies),
      fish meal (FM; 27/12) and rapeseed meal (RSM; 74/35) were used as a protein
      supplement. Increasing dietary CP concentration increased (P<0.01) BW gain (BWG),
      but the responses were quantitatively small (1.4 g per 1 g/kg dry matter (DM)
      increase in dietary CP concentration). The BWG responses were not different for
      bulls v. steers and heifers (1.4 v. 1.3 g per 1 g/kg DM increase in dietary CP
      concentration) and for dairy v. beef breeds (1.2 v. 1.7 g per 1 g/kg,
      respectively). The effect of increased CP concentration declined (P<0.01) with
      increasing mean BW of the animals and with improved BWG of the control animals
      (the lowest CP diet in each study). The BWG responses to protein supplementation
      were not related to the CP concentration in the control diet. The BWG responses
      increased (P<0.05) with increased ammonia N concentration in silage N and
      declined marginally (P>0.10) with increasing proportion of concentrate in the
      diet. All protein supplements had a significant effect on BWG, but the effects
      were greater for RSM (P<0.01) and FM (P<0.05) than for SBM. Increasing dietary CP
      concentration improved (P<0.01) feed efficiency when expressed as BWG/kg DM
      intake, but decreased markedly when expressed as BWG/kg CP intake. Assuming CP
      concentration of 170 g/kg BW marginal efficiency of the utilisation of
      incremental CP intake was only 0.05. Increasing dietary CP concentration had no
      effects on carcass weight, dressing proportion or conformation score, but it
      increased (P<0.01) fat score. Owing to limited production responses, higher
      prices of protein supplements compared with cereal grains and possible increases
      the N and P emissions, there is generally no benefit from using protein
      supplementation for growing cattle fed grass silage-based diets, provided that
      the supply of rumen-degradable protein is not limiting digestion in the rumen.

PMID- 24917149
TI  - Update on the genomics and basic biology of Brachypodium: International
      Brachypodium Initiative (IBI).
AB  - The scientific presentations at the First International Brachypodium Conference
      (abstracts available at http://www.brachy2013.unimore.it) are evidence of the
      widespread adoption of Brachypodium distachyon as a model system. Furthermore,
      the wide range of topics presented (genome evolution, roots, abiotic and biotic
      stress, comparative genomics, natural diversity, and cell walls) demonstrates
      that the Brachypodium research community has achieved a critical mass of tools
      and has transitioned from resource development to addressing biological
      questions, particularly those unique to grasses. 

PMID- 24917150
TI  - Selecting the quality of mule duck fatty liver based on near-infrared
      spectroscopy.
AB  - BACKGROUND: "Foie gras" is produced predominantly in France and about 90% of the
      commercialized product is obtained from male mule ducks. The melting rate
      (percentage of fat released during cooking) is the main criterion used to
      determine the quality of "foie gras". However, up to now the melting rate could
      not be predicted without causing liver damage, which means that selection
      programs could not use this criterion. METHODS: Fatty liver phenotypes were
      obtained for a population of over 1400 overfed male mule ducks. The phenotypes
      were based on two types of near-infrared spectra (on the liver surface and on
      ground liver) in order to predict the melting rate and liver composition (ash,
      dry matter, lipid and protein contents). Genetic parameters were computed in
      multiple traits with a "sire-dam" model and using a Gibbs sampling approach.
      RESULTS: The estimates for the genetic parameters show that the measured melting
      rate and the predicted melting rate obtained with two near-infrared spectrometer
      devices are genetically the same trait: genetic correlations are very high
      (ranging from +0.89 to +0.97 depending on the mule duck parental line and the
      spectrometer) and heritabilities are comparable. The predictions based on the
      spectra of ground liver samples using a laboratory spectrometer correlate with
      those based on the surface spectra using a portable spectrometer (from +0.83 to
      +0.95 for dry matter, lipid and protein content) and are particularly high for
      the melting rate (higher than +0.95). Although less accurate than the predictions
      obtained using the spectra of ground liver samples, the phenotypic prediction of
      the melting rate based on surface spectra is sufficiently accurate to be used by
      "foie gras" processors. CONCLUSIONS: Near-infrared spectrometry is an efficient
      tool to select liver quality in breeding programs because animals can be ranked
      according to their liver melting rate without damaging their livers. Thus, these
      original results will help breeders to select ducks based on the liver melting
      rate, a crucial criterion that defines the quality of the liver and for which
      there was previously no accurate predictor.

PMID- 24917151
TI  - Predicting climate change effects on surface soil organic carbon of Louisiana,
      USA.
AB  - This study aimed to assess the degree of potential temperature and precipitation
      change as predicted by the HadCM3 (Hadley Centre Coupled Model, version 3)
      climate model for Louisiana, and to investigate the effects of potential climate
      change on surface soil organic carbon (SOC) across Louisiana using the Rothamsted
      Carbon Model (RothC) and GIS techniques at the watershed scale. Climate data sets
      at a grid cell of 0.5 degrees  * 0.5 degrees  for the entire state of Louisiana
      were collected from the HadCM3 model output for three climate change scenarios:
      B2, A2, and A1F1, that represent low, higher, and even higher greenhouse gas
      emissions, respectively. Geo-referenced datasets including USDA-NRCS Soil
      Geographic Database (STATSGO), USGS Land Cover Dataset (NLCD), and the Louisiana
      watershed boundary data were gathered for SOC calculation at the watershed scale.
      A soil carbon turnover model, RothC, was used to simulate monthly changes in SOC
      from 2001 to 2100 under the projected temperature and precipitation changes. The
      simulated SOC changes in 253 watersheds from three time periods, 2001-2010, 2041
      2050, and 2091-2100, were tested for the influence of the land covers and
      emissions scenarios using SAS PROC GLIMMIX and PDMIX800 macro to separate Tukey
      Kramer (p < 0.01) adjusted means into letter comparisons. The study found that
      for most of the next 100 years in Louisiana, monthly mean temperature under all
      three emissions projections will increase; and monthly precipitation will,
      however, decrease. Under three emission scenarios, A1FI, A2, and B2, the mean SOC
      in the upper 30-cm depth of Louisiana forest soils will decrease from 33.0 t/ha
      in 2001 to 26.9, 28.4, and 29.2 t/ha in 2100, respectively; the mean SOC of
      Louisiana cropland soils will decrease from 44.4 t/ha in 2001 to 36.3, 38.4, and
      39.6 t/ha in 2100, respectively; the mean SOC of Louisiana grassland soils will
      change from 30.7 t/ha in 2001 to 25.4, 26.6, and 27.0 t/ha in 2100, respectively.
      Annual SOC changes will be significantly different among the land cover classes
      including evergreen forest, mixed forest, deciduous forest, small grains, row
      crops, and pasture/hay (p < 0.0001), emissions scenarios (p < 0.0001), and their
      interactions (p < 0.0001).

PMID- 24917152
TI  - Cdk5 phosphorylation of EFhd2 at S74 affects its calcium binding activity.
AB  - EFhd2 is a calcium binding protein, which is highly expressed in the central
      nervous system and associated with pathological forms of tau proteins in
      tauopathies. Previous phosphoproteomics studies and bioinformatics analysis
      suggest that EFhd2 may be phosphorylated. Here, we determine whether Cdk5, a
      hyperactivated kinase in tauopathies, phosphorylates EFhd2 and influence its
      known molecular activities. The results indicated that EFhd2 is phosphorylated by
      brain extract of the transgenic mouse CK-p25, which overexpresses the Cdk5
      constitutive activator p25. Consistently, in vitro kinase assays demonstrated
      that Cdk5, but not GSK3beta, directly phosphorylates EFhd2. Biomass, tandem mass
      spectrometry, and mutagenesis analyses indicated that Cdk5 monophosphorylates
      EFhd2 at S74, but not the adjacent S76. Furthermore, Cdk5-mediated
      phosphorylation of EFhd2 affected its calcium binding activity. Finally, a
      phospho-specific antibody was generated against EFhd2 phosphorylated at S74 and
      was used to detect this phosphorylation event in postmortem brain tissue from
      Alzheimer's disease and normal-aging control cases. Results demonstrated that
      EFhd2 is phosphorylated in vivo at S74. These results imply that EFhd2's
      physiological and/or pathological function could be regulated by its
      phosphorylation state. 

PMID- 24917153
TI  - Low-intensity running exercise enhances the capillary volume and pro-angiogenic
      factors in the soleus muscle of type 2 diabetic rats.
AB  - INTRODUCTION: We determined the effects of low-intensity exercise on the three
      dimensional capillary structure and associated angiogenic factors in the soleus
      muscle of Goto-Kakizaki (GK) diabetic rats. METHODS: Four groups of male rats
      were studied: sedentary nondiabetic (Con), exercised nondiabetic control (Ex),
      sedentary GK, and exercised GK (GK+Ex). Rats in the Ex and GK+Ex groups were
      subjected to chronic low-intensity running on a treadmill (15 m/min, 60
      min/session, 5 sessions/week for 3 weeks). RESULTS: Although mean capillary
      volume and diameter were lower in the GK compared with all other groups, low
      intensity exercise increased both of these measures in GK rats. Mitochondrial
      markers, i.e., SDH activity and PGC-1alpha expression, and the levels of
      angiogenic factors were higher in the GK+Ex than all other groups. Exercise
      increased vascular endothelial growth factor (VEGF) protein levels and the VEGF
      to-TSP-1 ratio, an indicator of angiogenesis, in GK rats. CONCLUSIONS: Combined,
      the results indicate that low-intensity exercise reduces some of the
      microcirculatory complications in type 2 diabetic muscles.

PMID- 24917154
TI  - [A study of the usefulness of flow-adjustable bilateral pulmonary artery banding
      (FABPAB) for hypoplastic left heart syndrome( HLHS) or HLHS variant].
AB  - BACKGROUNDS: Bilateral pulmonary artery banding( BPAB), a relatively minimally
      invasive procedure, has begun to be undertaken as the initial operation for the
      treatment of hypoplastic left heart syndrome (HLHS) or HLHS variant. In the
      opinion of the present authors, it is practicable to avoid stepwise operations
      with cardiopulmonary bypass (CPB) in newborn patients by conducting an initial
      operation consisting of flow-adjustable bilateral pulmonary artery banding
      (FABPAB) combined with transcatheter pulmonary artery balloon dilatation( PABD),
      followed in a subsequent treatment course by transcatheter PABD, which would
      allow for more minimally invasive adjustment of the pulmonary artery bloodflow.
      This study was conducted as a retrospective evaluation of the usefulness of this
      therapeutic strategy. METHODS: Fourteen patients who underwent BPAB as the
      initial operation for HLHS/HLHS variant between April 2008 and October 2013 were
      included in this study. Stepwise surgical repair including BPAB was performed via
      a median sternotomy as the initial operation, without the use of CPB. And 7
      patients underwent transcatheter PABD successfully. RESULTS: In this series, 7
      patients developed a significant pulmonary artery index (PAI) after PABD (pre
      PABD:148.3+/-63.9 vs. post PABD:232.5+/-73.2, p<0.05). No need of the pulmonary
      artery reconstruction at the 2nd operation. One patient failed to survive the
      operation, in which difficulty in adjustment of atrioventricular valvular
      regurgitation was encountered after the Norwood procedure. There were 3 patients
      who underwent the Norwood combined BDG at the mean age of 4.6 months and the mean
      body weight of 5.5 kg. Fontan procedure was accomplished in 3 of the 6 patients
      of the survivor, while 3 patients were on standby for the Fontan procedure.
      CONCLUSION: We performed BPAB as the initial operation combined with PABD in the
      treatment of HLHS/HLHS variant, which enabled avoidance of the initial operation
      with cardiopulmonary bypass at the neonatal stage and developed a significant
      pulmonary artery index after PABD.

PMID- 24917155
TI  - [Bilateral pulmonary artery banding using ligation clips and facile Norwood-Glenn
      procedure].
AB  - Bilateral pulmonary artery banding( BPAB), though a less-invasive surgical option
      for hypoplastic left heart syndrome (HLHS), entails considerable risk of residual
      pulmonary artery stenosis after de-banding. Autologous aortic reconstruction in
      Norwood procedure is attractive in terms of growth potential, but technically
      demanding. To overcome these drawbacks, we modified the 2 techniques. Eight
      patients with HLHS underwent BPAB whereby ligation clips were half-closed into
      rhombic shape to deform bilateral pulmonary arteries. The arterial duct was kept
      patent by prostaglandin E1 infusion. One patient died of sepsis( age 8 months),
      while the 7 survivors underwent Norwood-Glenn procedure. Both pulmonary arteries
      were excised from the pulmonary trunk with minimal cuffs. Resultant defect in the
      pulmonary trunk was longitudinally closed. After arterial duct excision,
      pulmonary trunk-to descending aorta continuity was reconstructed by end-to-end
      anastomosis. Ascending aorta-to-aortic arch complex was anastomosed to the
      pulmonary trunk in a side-to-side fashion. After bilateral pulmonary artery
      continuity was reconstructed, Glenn anastomosis was made. One patient died of
      pneumonia(age 5 months). Currently, the 6 surviving patients(age 4~30 months),
      enjoy good health. Four of them have completed Fontan procedure. Our modified
      techniques are facile, reproducible, and pose low risk of residual pulmonary
      artery stenosis or aortic stenosis.

PMID- 24917156
TI  - [Reconstruction of pulmonary blood flow in the Norwood procedure; Blalock-Taussig
      shunt; from bench to surgery].
AB  - Although the right-ventricle to pulmonary artery( RV-PA) shunt as a source of
      pulmonary blood supply of Norwood procedure has improved early outcomes,
      disadvantages including right ventricular dysfunction or arrhythmias have been
      reported. So it has been still remained controversial whether BT shunt or RV-PA
      conduit should be selected. We examined the influence of Blalock-Taussig( BT)
      shunt size on regulation of the pulmonary blood flow in experimental model of a
      univentricular heart to determine the specific guidelines regarding suitable
      shunt size in the Norwood procedure. The canine univentricular heart model with
      the ratio of shunt size to body weight (SS/BW) of 0.8 to 1.1 showed significant
      negative correlation between the pulmonary/systemic blood flow ratio( Qp/Qs)and
      arterial PCo2, but those with SS/BW of 1.1 to 1.4 did not. Similar phenomena were
      shown with the grouped data on relationship between the Qp/Qs and inspired oxygen
      fraction. These findings imply that when SS/BW is 0.8 to 1.1, the Qp/Qs is
      controllable by physiologic respiratory manipulations. In the context of our
      clinical experiences, SS/BW of 0.9 to 1.0 is considered a useful index for
      suitable BT shunt in the Norwood procedure. 

PMID- 24917157
TI  - [Impacts of bilateral pulmonary artery banding on the surgical and long-term
      outcomes in hypoplastic left heart syndrome( HLHS) and its variants].
AB  - Although Norwood-type operation is a fundamental procedure for hypoplastic left
      heart syndrome and its variants, the surgical risk is still high even in the high
      volume center. Bilateral pulmonary artery (PA) banding( BPAB) is an alternative
      procedure to avoid the risk in the neonatal period. We clarified the impacts of
      BPAB on the surgical and long-term outcomes in HLHS and its variants. Consecutive
      85 patients( classical HLHS:52, variant:33) who underwent surgical intervention
      between July, 1993 and December, 2012 were evaluated. Fetal diagnosis was done in
      37 patients (44%). Forty-two patients underwent primary Norwood operation[ Gp N,
      Blalock-Taussig( BT):29, right-ventricle( RV)-PA conduit:13] and the remaining 43
      patients underwent BPAB followed by Norwood operation. Among them, 4 patients did
      not reach Norwood [9%, atrioventricular valve regurgitation (AVVR):1,
      infection:1, preoperative shock:2). The survived 39 patients were divided into 2
      groups;Gp BN (BPAB -> Norwood+BT/RV-PA conduit, n=22), Gp BG [BPAB ->
      Norwood+bidirectional Glenn procedure(BDG), n=17]. BPAB for HLHS and its variants
      is useful in terms of lower mortality. The 2nd stage palliation is so important
      that modified Norwood procedure with BT shunt or RV-PA conduit contribute to the
      lower morbidity including neurological outcome. Norwood+BDG strategy might be
      beneficial for the high risk patients such as with poor cardiac function or low
      body weight.

PMID- 24917158
TI  - [Treatment strategy toward Fontan completion in hypoplastic left heart syndrome].
AB  - The Norwood procedure with right ventricle-pulmonary artery (RV-PA) conduit is
      thought to improve post-operative hemodynamics in hypoplastic left heart
      syndrome( HLHS). Prematurity( GA<37 weeks), body weight less than 2.5 kg and
      tricuspid regurgitation( TR)2+ or more were associated with mortality. For
      requiring better outcome, paralyzed ventilation, inherent N2 are indicated, to
      avoid preoperative high pulmonary blood flow followed by progressive TR. Rapid
      staged bilateral pulmonary artery banding( PAB) might improve the outcome for
      this high mortality group. As operative improvement, the distal neoaortic
      reconstruction was completed without any patch materials in most case. For
      achievement this, it is important that aortic arch and ascending aorta just
      opposite the site of the innominate artery were sutured inferiorly to extend the
      width of the aortic arch. Also we have developed a modified strategy to control
      RV-PA shunt flow, which is partial clipping on the ePTFE graft. Because
      significant TR associated with mortality, TR should be surgically treated at any
      sage of reconstruction. At bidirectional Glenn operation, 70% of patient were
      left the RV-PA conduit as additional flow. Hospital mortality after Fontan
      completion for HLHS is excellent with short averaging more than 95%. Extracardiac
      conduit with fenestration is indicated in all HLHS patients. 

PMID- 24917159
TI  - [Improvement of outcomes in the surgical treatment of hypoplastic left heart
      syndrome (HLHS) with staged Norwood operation].
AB  - On behalf of rapid progress of diagnostic technologies and new development of
      surgical technique or strategy, outcomes of surgical treatment of hypoplastic
      left heart syndrome (HLHS) has remarkably improved in the current practice. One
      of such approaches is the staged Norwood operation. We have reviewed our patients
      (n=54) between 2003 and 2013. A half of the patients with the staged group
      accomplished Norwood procedure and concomitant bidirectional cavopulmonary shunt
      at the mean age of 4 months old. An another half of the patients underwent
      secondary Norwood operation with Blalock-Taussig( BT) shunt or right-ventricle to
      pulmonary artery( RV-PA) conduit, because of ductal closure in spite of
      prostaglandin, or progressive reversed coarctation. Cardiac catheterization
      showed good results in both the primary (n=17) and the staged approach (n=37),
      partly because even in the primary Norwood group we used a smaller calibered
      graft for BT shunt or RV-PA conduit to unload the ventricle as much as possible.
      In conclusion, since the surgical mortality of staged group was superior to that
      of the primary group and the mid-term survival in the staged seemed to be better
      than that of primary, we would pursue our strategy of the staged approach in the
      surgical treatment of hypoplastic left heart syndrome. 

PMID- 24917160
TI  - [Surgical strategy and the results for hypoplastic left heart syndrome].
AB  - OBJECTIVE: We retrospectively reviewed our surgical results in patients with
      hypoplastic left heart syndrome( HLHS) to investigate the influence of surgical
      strategy on outcome. METHODS: Seventy-seven patients with classic HLHS were
      involved in this study. For the initial palliation, 23 patients underwent Norwood
      operation with modified Blalock-Taussig (BT) shunt, 23 patients underwent Norwood
      operation with right ventricle to pulmonary artery( RV-PA) shunt and 31 patients
      underwent bilateral pulmonary artery banding (BPAB). Surgical results, freedom
      from Fontan operation, hemodynamic data and incidence of complication after
      Fontan operation were compared between the 3 groups. RESULTS: BPAB group had more
      preoperative risk factors than Norwood group. Total actuarial survival was 62.4%
      at 1 year and 58.2% at 3 and 5 years, and there was no difference between the
      groups. Freedom from Fontan completion was 59.4% at 3 years and 48.7% at 5 years
      without difference between the groups. The incidence of intervention for
      pulmonary artery stenosis was higher in Norwood with RV-PA shunt group(52.9%).
      Hemodynamic data obtained by cardiac catheterization were similar in the 3
      groups, however, end-systolic elastance, which represents ventricular
      contractility, was lower in Norwood with RV-PA group. CONCLUSIONS: Surgical
      results of Norwood with BT shunt and Norwood with RV-PA shunt were comparably
      satisfactory, however, there was possible concern of reduced ventricular
      contractility in RV-PA shunt group. BPAB was a effective and useful initial
      palliation in high risk cases.

PMID- 24917161
TI  - [The treatment strategy for hypoplastic left heart syndrome].
AB  - In the recent years, the outcomes of treatment for hypoplastic left heart
      syndrome (HLHS) is improved because of perioperative management and procedure. We
      adopt a strategy of the primary Norwood procedure basically for neonates with
      HLHS, however bilateral pulmonary artery banding precede in patients with risk
      factors. In the Norwood procedure, aortic arch is reconstructed without
      artificial prostheses and pulmonary blood flow is supplied from the Blalock
      Taussig shunt or the right ventricle-pulmonary artery shunt by case. We
      administer high dose vasodilators and nitric oxide gas with low resistance
      strategy after the Norwood procedure. The survival rate of patients with HLHS
      after 2005 is 84.2% in this strategy.

PMID- 24917162
TI  - [Empyema that was diagnosed as primary ciliary dyskinesia by electron
      microscopical image of nasal mucosa].
AB  - A patient was 17-year-old. She had a history of repeated pneumonia and sinusitis.
      She was admitted to our hospital with the diagnosis of pneumonia. Although she
      was prescribed a course of antibiotics, chest roentgenogram and computed
      tomography showed increased and capselized pleural effusion, suggesting the
      development of acute empyema. Capsulized effusion and pus in thorax were removed
      by surgery. A part of lingular segment was raptured necessitating the partial
      resection of lingular segment. Her postoperative course was well. Her history of
      repeated pneumonia and sinusitis indicated the existence of primary ciliary
      dyskinesia, and the biopsy of nasal mucosa was done. The electron microscopical
      image of nasal mucosa showed defect of inner dynein arm. We made a diagnosis of
      primary ciliary dyskinesia based on her previous history and electron
      microscopical image. 

PMID- 24917163
TI  - [Video-assisted thoracoscopic surgery for intrathoracic extramedullary
      hematopoiesis].
AB  - Extramedullary hematopoiesis (EMH) is associated with hematopoietic disorders,
      with intrathoracic EMH being a rare presentation. We report a case of posterior
      mediastinal EMH masses in 63-year-old male with congenital hemolytic anemia.
      Multiple paravertebral masses with dense soft parts and well defined borders, but
      without accompanying calcification or bone erosion were identified on a chest
      computed tomography (CT) scan during an examination for another disease. A left
      posterior mediastinal mass was resected using video-assisted thoracoscopic
      surgery. Post-operative pathological examination showed that the tumor was
      covered completely by a capsule, and composed of mature adipose tissue and
      hematopoietic tissue including erythroblasts and myeloid cells. Based on these
      findings we diagnosed intrathoracic EMH.

PMID- 24917164
TI  - [A patient with descending necrotizing mediastinitis successfully treated by
      cervical, transthoracic, and mediastinoscopic drainage].
AB  - A 62-year-old man was admitted to a local hospital for cervical abscess. He was
      given an antibiotic, but his symptoms worsened. Computed tomographic cervical and
      chest scan 6 days after hospitalization revealed that left cervical abscess
      extended to the mediastinum. He was transferred to our hospital following a
      diagnosis of descending necrotizing mediastinitis. Cervical and left
      transthoracic drainage through a left cervical incision and a left antero
      axillary thoracotomy were performed on hospital day 1. On hospital day 2, chest
      radiograph revealed enlargement of the superior mediastinal shadow.
      Mediastinoscopic drainage was performed for the abscess in the paratracheal space
      on hospital day 3. Two mediastinal drainage tubes were placed in the upper and
      middle mediastinal space using mediastioscopy. Postoperatively, he required
      additional right transthoracic drainage by chest tube for pleural effusion on
      hospital day 5. Then his clinical and radiological findings gradually improved,
      and he was discharged from hospital day 37. 

PMID- 24917165
TI  - [Cutaneous metastasis from lung adenocarcinoma resected 34 months before
      surviving 5-year after skin tumor resection without relapse].
AB  - A 79-year-old man complained incurable skin ulcer that was treated in the
      neighborhood hospital during 2 months. He had been undergone right upper
      lobectomy for the lung adenocarcinoma in our hospital 34 months ago. The skin
      lesion in the right axilla was an elastic hard tumor about 2 cm large in
      thesubcutaneous tissue with ulceration, and was diagnosed as adenocarcinoma by
      cytology. Fluorodeoxy glucose-positron emission tomography (FDG-PET) /computed
      tomography (CT) showed no metastatic lesion other than the skin tumor, and the
      tumor was resected with a margin. Immunohistochemistry [cytokeratin (CK)-7(+++),
      CK-20(-), thyroid transcription factor (TTF)-1(-)] indicated the skin tumor to be
      metastasis from lung adenocarcinoma. He is alive over 8 years after right upper
      lobectomy(RUL)and 5 years after skin tumor resection without relapse. 

PMID- 24917166
TI  - [Solitary pulmonary metastasis of low-grade uterine endometrial stromal sarcoma
      resected 31 years before].
AB  - A 74-year-old female underwent hysterectomy and bilateral ovariectomy for uterine
      endometrial stromal sarcoma( ESS), low grade, at another hospital 31 years
      previously. When the patient was admitted for pneumonia, a lung tumor was pointed
      out on her chest X-ray and computed tomography( CT) scan. Chest X-ray showed an
      oval figure shadow of about 3.5 cm in diameter in the right lower lung
      field.Chest CT scan revealed an irregular form tumor of 3.5 cm in diameter in the
      right S8 of the lung. Fluorodeoxyglucose-positron emission tomography (FDG-PET)
      scan identified an abnormal accumulation of FDG at the tumor site. A pulmonary
      metastasis of the ESS was suspected by transbronchial lung biopsy, and the
      patient underwent the thoracoscopic partial resection of the right lower lobe of
      the lung.Histologically, the tumor was diagnosed as metastasis of the ESS, low
      grade. 

PMID- 24917167
TI  - [Three cases of spontaneous pneumothorax by ruptured paravertebral gourd-shaped
      bullae].
AB  - We reported 3 elderly patients with right pneumothorax caused by ruptured
      paravertebral gourdshaped bullae. Two patients showed the characteristic symptom
      of air leakage of this type of pneumothorax, which decreased in the supine
      position, but increased in the sitting position. Chest computed tomography
      imaging showed bullae spreading in the space of the azygoesophageal recess. All
      patients underwent video-assisted thoracic surgery (VATS), and 2 patients
      underwent mini-thoracotomy because of adhesion and pyothorax. Ruptured bullae
      with stalks were found at the mediastinal sides of their right lower lobes in all
      patients. Bullectomy using an endoscopic stapler or ligation at the bulla root
      was performed easily and safely. The right pneumothorax caused by ruptured
      paravertebral gourd-shaped bulla was considered to be a good indication for the
      VATS due to the unique shape of the bulla, which has a stalk at its root. 

PMID- 24917168
TI  - [Simultaneous bilateral spontaneous pneumothorax; report of a case].
AB  - Simultaneous bilateral spontaneous pneumothorax (SBSP) occurred in a 16-year-old
      male. He presented with severe dyspnea. Chest X-ray showed bilateral
      pneumothorax. Computed tomography revealed bilateral apical bullas. Chest tubes
      were promptly inserted bilaterally. The patient underwent single-stage bilateral
      video-assisted thoracoscopic surgery( VATS). Bilateral bullectomy was performed
      sequentially. Saline poured in to test for air leakage did not escape to the
      opposite pleural cavity, suggesting no pleuro-pleural communication. Post
      operative course was uneventful. A bilateral single-stage VATS by a conventional
      lateral approach with intra-operative patient repositioning is a safe, feasible
      and familiar technique for treatment of SBSP. 

PMID- 24917169
TI  - A novel method for simulating insulin mediated GLUT4 translocation.
AB  - Glucose transport in humans is a vital process which is tightly regulated by the
      endocrine system. Specifically, the insulin hormone triggers a cascade of
      intracellular signals in target cells mediating the uptake of glucose. Insulin
      signaling triggers cellular relocalization of the glucose transporter protein
      GLUT4 to the cell surface, which is primarily responsible for regulated glucose
      import. Pathology associated with the disruption of this pathway can lead to
      metabolic disorders, such as type II diabetes mellitus, characterized by the
      failure of cells to appropriately uptake glucose from the blood. We describe a
      novel simulation tool of the insulin intracellular response, incorporating the
      latest findings regarding As160 and GEF interactions. The simulation tool differs
      from previous computational approaches which employ algebraic or differential
      equations; instead, the tool incorporates statistical variations of kinetic
      constants and initial molecular concentrations which more accurately mimic the
      intracellular environment. Using this approach, we successfully recapitulate
      observed in vitro insulin responses, plus the effects of Wortmannin-like
      inhibition of the pathway. The developed tool provides insight into transient
      changes in molecule concentrations throughout the insulin signaling pathway, and
      may be employed to identify or evaluate potentially critical components of this
      pathway, including those associated with insulin resistance. In the future, this
      highly tractable platform may be useful for simulating other complex cell
      signaling pathways. Biotechnol. Bioeng. 2014;111: 2454-2465. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 24917170
TI  - Modulation of the startle reflex by heat pain: does threat play a role?
AB  - BACKGROUND: Previous studies have indicated that the startle reflex is
      potentiated by phasic, but not by tonic, heat pain, although the latter is seen
      as more strongly associated with emotional responses and more similar to clinical
      pain. The threat value of pain might be a decisive variable, which is not
      influenced alone by stimulus duration. OBJECTIVE: This study aimed at comparing
      startle responses to tonic heat pain stimulation with varying degrees of threat.
      We hypothesized that the expectation of unpredictable temperature increases would
      evoke higher threat and thereby potentiate startle compared with the expectation
      of constant stimulation. METHODS: Healthy, pain-free subjects (n = 40) underwent
      painful stimulation in two conditions (low/high threat) in balanced order. The
      only difference between the two conditions was that in the high-threat condition
      50% of the trials were announced to include a short further noxious temperature
      increase at the end. Startle tones were presented prior to this temperature
      increase still in the phase of anticipation. RESULTS: We observed startle
      potentiation in the high-threat compared with the low-threat condition, but only
      in those participants who took part first in the high-threat condition.
      Habituation could not account for these findings, as we detected no significant
      decline of startle responses in the course of both conditions. CONCLUSIONS: Our
      results suggest that subjective threat might indeed be decisive for the action of
      pain on startle; the threat level appears not only influenced by actual
      expectations but also by previous experiences with pain as threatening or not.

PMID- 24917171
TI  - Albino midrib 1, encoding a putative potassium efflux antiporter, affects
      chloroplast development and drought tolerance in rice.
AB  - KEY MESSAGE: Mutation of the AM1 gene causes an albino midrib phenotype and
      enhances tolerance to drought in rice K(+) efflux antiporter (KEA) genes encode
      putative potassium efflux antiporters that are mainly located in plastid
      containing organisms, ranging from lower green algae to higher flowering plants.
      However, little genetic evidence has been provided on the functions of KEA in
      chloroplast development. In this study, we isolated a rice mutant, albino midrib
      1 (am1), with green- and white-variegation in the first few leaves, and albino
      midrib phenotype in older tissues. We found that AM1 encoded a putative KEA in
      chloroplast. AM1 was highly expressed in leaves, while lowly in roots.
      Chloroplast gene expression and proteins accumulation were affected during
      chlorophyll biosynthesis and photosynthesis in am1 mutants. Interestingly, AM1
      was induced by salt and PEG, and am1 showed enhanced sensitivity to salinity in
      seed germination and increased tolerance to drought. Taken together, we concluded
      that KEAs were involved in chloroplast development and played important roles in
      drought tolerance.

PMID- 24917172
TI  - Timing of the G1/S transition in tobacco pollen vegetative cells as a primary
      step towards androgenesis in vitro.
AB  - KEY MESSAGE: Mid-bicellular pollen vegetative cells in tobacco escape from G1
      arrest and proceed to the G1/S transition towards androgenesis within 1 day under
      glutamine starvation conditions in vitro. In the Nicotiana tabacum pollen culture
      system, immature pollen grains at the mid-bicellular stage can mature in the
      presence of glutamine; however, if glutamine is absent, they deviate from their
      native cell fate in a few days. The glutamine-starved pollen grains cannot
      undergo maturation, even when supplied with glutamine later. Instead, they
      undergo cell division towards androgenesis slowly within 10 days in a medium
      containing appropriate nutrients. During the culture period, they ought to escape
      from G1 arrest to proceed into S phase as the primary step towards androgenesis.
      However, this event has not been experimentally confirmed. Here, we demonstrated
      that the pollen vegetative cells proceeded to the G1/S transition within
      approximately 15-36 h after the start of culture. These results were obtained by
      analyzing transgenic pollen possessing a fusion gene encoding nuclear-localizing
      GFP under the control of an E2F motif-containing promoter isolated from a gene
      encoding one of DNA replication licensing factors. Observations using a 5-ethynyl
      2'-deoxyuridine DNA labeling and detection technique uncovered that the G1/S
      transition was soon followed by S phase. These hallmarks of vegetative cells
      undergoing dedifferentiation give us new insights into upstream events causing
      the G1/S transition and also provide a novel strategy to increase the frequency
      of the androgenic response in tobacco and other species, including recalcitrants.

PMID- 24917173
TI  - Crowdsourcing, the great meteor storm of 1833, and the founding of meteor
      science.
AB  - Yale science professor Denison Olmsted used crowdsourcing to gather observations
      from across the United States of the unexpected deluge of meteors on 13 November
      1833--more than 72,000/h. He used these observations (and newspaper accounts and
      correspondence from scientists) to make a commendably accurate interpretation of
      the meteor storm, overturning 2100 years of erroneous teachings about shooting
      stars and establishing meteor science as a new branch of astronomy. Olmsted's
      success was substantially based on his use of newspapers and their practice of
      news pooling to solicit observations from throughout the country by lay and
      expert observers professionally unaffiliated with Yale College and him. In
      today's parlance, Olmsted was a remarkably successful early practitioner of
      scientific crowdsourcing, also known as citizen science. He may have been the
      first to use mass media for crowdsourcing in science. He pioneered many of the
      citizen-science crowdsourcing practices that are still in use today: an open call
      for citizen participation, a clearly defined task, a large geographical
      distribution for gathering data and a rapid response to opportunistic events.
      Olmsted's achievement is not just that he used crowdsourcing in 1833 but that
      crowdsourcing helped him to advance science significantly.

PMID- 24917174
TI  - Clinical efficacy of immediate implant loading protocols compared to conventional
      loading depending on the type of the restoration: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Immediate loading has become a predictable option to
      restore all clinical situations. The aim of this systematic review was to assess
      whether immediate loading protocols achieve comparable clinical outcomes when
      compared to conventional loading protocols depending on the type of prosthetic
      restoration. METHODS: A protocol was developed aimed to answer the following
      focused question: "What are the effects of immediate implant loading protocols
      compared to conventional implant loading, in terms of implant failure, marginal
      bone levels, and biological and mechanical complications based on the type of
      restoration?" The next subanalysis were performed as follows: the extent, type,
      and material of the restoration and the type of occlusal contact in function.
      This systematic review only included randomized controlled trials (RCTs) with a
      follow-up of at least 6 months after implant loading. RESULTS: Thirty-seven final
      papers were included. The results from the meta-analyses have shown that the
      immediately loading implants demonstrated a statistically significant higher risk
      of implant failure [RR = 1.92; 95% CI (1.04; 3.54); P = 0.036], a statistically
      significant lower bone loss [WMD = 0.046; 95% CI (0.043; 0.049); P = 0.000] and a
      smaller increase in ISQ values [WMD = -1.096; 95% CI (-1.615; -0.577); P < 0.001,
      although both groups attained high survival rates (98.2% in the test and 99.6% in
      the control). Single teeth implants were greater risk of failure, when compared
      to immediately loaded full arch restorations (RR = 2 vs. 0.9), so as the occlusal
      pattern when compared to non-occlusal (RR = 1.9 vs. 1.4). CONCLUSIONS: Immediate
      loading may impose a greater risk for implant failure when compared to
      conventional loading, although the survival rates were high for both groups.

PMID- 24917175
TI  - Individual selection of gait retraining strategies is essential to optimally
      reduce medial knee load during gait.
AB  - BACKGROUND: The progression of medial knee osteoarthritis seems closely related
      to a high external knee adduction moment, which could be reduced through gait
      retraining. We aimed to determine the retraining strategy that reduces this knee
      moment most effective during gait, and to determine if the same strategy is the
      most effective for everyone. METHODS: Thirty-seven healthy participants underwent
      3D gait analysis. After normal walking was recorded, participants received verbal
      instructions on four gait strategies (Trunk Lean, Medial Thrust, Reduced Vertical
      Acceleration, Toe Out). Knee adduction moment and strategy-specific kinematics
      were calculated for all conditions. FINDINGS: The overall knee adduction moment
      peak was reduced by Medial Thrust (-0.08Nm/Bw.Ht) and Trunk Lean (-0.07Nm/Bw.Ht),
      while impulse was reduced by 0.03Nms/Bw.Ht in both conditions. Toeing out reduced
      late stance peak and impulse significantly but overall peak was not affected.
      Reducing vertical acceleration at initial contact did not reduce the overall
      peak. Strategy-specific kinematics (trunk lean angle, knee adduction angle, first
      peak of the vertical ground reaction force, foot progression angle) showed that
      multiple parameters were affected by all conditions. Medial Thrust was the most
      effective strategy in 43% of the participants, while Trunk Lean reduced external
      knee adduction moment most in 49%. With similar kinematics, the reduction of the
      knee adduction moment peak and impulse was significantly different between these
      groups. INTERPRETATION: Although Trunk Lean and Medial Thrust reduced the
      external knee adduction moment overall, individual selection of gait retraining
      strategy seems vital to optimally reduce dynamic knee load during gait.

PMID- 24917176
TI  - Ossifying fibroma in Buschke-Ollendorff syndrome.
AB  - Buschke-Ollendorff syndrome represents an autosomal dominant disorder
      characterized by connective tissue nevi and osteopoikilosis. Cutaneous lesions
      may contain either predominantly elastic fibers or predominantly collagen fibers
      or may show both connective tissue components. The disease results from mutations
      in LEMD3 (MAN1), which lead to enhanced transforming growth factor-beta (TGF
      beta) signaling and resultant changes in fibroblast function. TGF-beta
      alterations have been implicated in a number of fibrotic disorders, and it is
      therefore not surprising that a range of cutaneous and skeletal abnormalities
      have been associated with Buschke-Ollendorff syndrome. Herein, we report a novel
      association between ossifying fibroma and Buschke-Ollendorff syndrome and discuss
      how these conditions are likely to be mechanistically linked. 

PMID- 24917177
TI  - Platelet-monocyte aggregate formation and mortality risk in older patients with
      severe sepsis and septic shock.
AB  - BACKGROUND: Aging-related changes in platelet and monocyte interactions may
      contribute to adverse outcomes in sepsis but remain relatively unexamined. We
      hypothesized that differential platelet-monocyte aggregate (PMA) formation in
      older septic patients alters inflammatory responses and mortality. METHODS: We
      prospectively studied 113 septic adults admitted to the intensive care unit with
      severe sepsis or septic shock. Patients were dichotomized a priori into one of
      two groups: older (age >= 65 years, n = 28) and younger (age < 65 years, n = 85).
      PMA levels were measured in whole blood via flow cytometry within 24 hours of
      admission. Plasma levels of IL-6 and IL-8, proinflammatory cytokines produced by
      monocytes upon PMA formation, were determined by commercial assays. Patients were
      followed for the primary outcome of 28-day, all-cause mortality. RESULTS:
      Elevated PMA levels were associated with an increased risk of mortality in older
      septic patients (hazard ratio for mortality 5.64, 95% confidence interval 0.64
      49.61). This association remained after adjusting for potential confounding
      variables in multivariate regression. Receiver operating curve analyses
      demonstrated that PMA levels greater than or equal to 8.43% best predicted 28-day
      mortality in older septic patients (area under the receiver operating curve
      0.82). Plasma IL-6 and IL-8 levels were also significantly higher in older
      nonsurvivors. In younger patients, neither PMA levels nor plasma monokines were
      significantly associated with mortality. CONCLUSIONS: Increased PMA formation,
      and associated proinflammatory monokine synthesis, predicts mortality in older
      septic patients. Although larger studies are needed, our findings suggest that
      heightened PMA formation in older septic patients may contribute to injurious
      inflammatory responses and an increased risk of mortality.

PMID- 24917178
TI  - Effects of Low-Load, Elastic Band Resistance Training Combined With Blood Flow
      Restriction on Muscle Size and Arterial Stiffness in Older Adults.
AB  - We examined the effect of low-load, elastic band resistance training with blood
      flow restriction (BFR) on muscle size and arterial stiffness in older adults.
      Healthy older adults (aged 61-85 years) were divided into BFR training (BFR-T, n
      = 9) or non-BFR training (CON-T, n = 8) groups. Both groups performed low-load
      arm curl and triceps down exercises (four sets, total 75 repetitions for each)
      using an elastic band, 2 d/wk for 12 weeks. The BFR-T group wore inflated
      pneumatic elastic cuffs (120-270 mm Hg) on both arms during training. Magnetic
      resonance imaging-measured muscle cross-sectional area of the upper arm, maximum
      voluntary isometric contraction of the elbow flexors and extensors, cardio-ankle
      vascular index testing, and ankle-brachial pressure index were measured before
      and 3-5 days after the final training session. Muscle cross-sectional area of the
      elbow flexors (17.6%) and extensors (17.4%) increased, as did elbow flexion and
      elbow extension maximum voluntary isometric contraction (7.8% and 16.1%,
      respectively) improved (p < .05) in the BFR-T group, but not in the CON-T group.
      In cardio-ankle vascular index and ankle-brachial pressure index testing, there
      were no changes between pre- and post-results in either group. In conclusion,
      elastic band BFR-T improves muscle cross-sectional area as well as maximal muscle
      strength but does not negatively affect arterial stiffness in older adults.

PMID- 24917179
TI  - A mechanistic pharmacokinetic model elucidating the disposition of trastuzumab
      emtansine (T-DM1), an antibody-drug conjugate (ADC) for treatment of metastatic
      breast cancer.
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) therapeutic for
      treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers.
      The T-DM1 dose product contains a mixture of drug-to-antibody ratio (DAR)
      moieties whereby the small molecule DM1 is chemically conjugated to trastuzumab
      antibody. The pharmacokinetics (PK) underlying this system and other ADCs are
      complex and have not been elucidated. Accordingly, we have developed two PK
      modeling approaches from preclinical data to conceptualize and understand T-DM1
      PK, to quantify rates of DM1 deconjugation, and to elucidate the link between
      trastuzumab, T-DM1, and DAR measurements. Preclinical data included PK studies in
      rats (n = 34) and cynomolgus monkeys (n = 18) at doses ranging from 0.3 to 30
      mg/kg and in vitro plasma stability. T-DM1 and total trastuzumab (TT) plasma
      concentrations were measured by enzyme-linked immunosorbent assay. Individual DAR
      moieties were measured by affinity capture liquid chromatography-mass
      spectrophotometry. Two PK modeling approaches were developed for T-DM1 using
      NONMEM 7.2 software: a mechanistic model fit simultaneously to TT and DAR
      concentrations and a reduced model fit simultaneously to TT and T-DM1
      concentrations. DAR moieties were well described with a three-compartmental model
      and DM1 deconjugation in the central compartment. DM1 deconjugated fastest from
      the more highly loaded trastuzumab molecules (i.e., DAR moieties that are >=3 DM1
      per trastuzumab). T-DM1 clearance (CL) was 2-fold faster than TT CL due to
      deconjugation. The two modeling approaches provide flexibility based on available
      analytical measurements for T-DM1 and a framework for designing ADC studies and
      PK-pharmacodynamic modeling of ADC efficacy- and toxicity-related endpoints.

PMID- 24917180
TI  - Diurnal variation in P-glycoprotein-mediated transport and cerebrospinal fluid
      turnover in the brain.
AB  - Nearly all bodily processes exhibit circadian rhythmicity. As a consequence, the
      pharmacokinetic and pharmacodynamic properties of a drug may also vary with time
      of day. The objective of this study was to investigate diurnal variation in
      processes that regulate drug concentrations in the brain, focusing on P
      glycoprotein (P-gp). This efflux transporter limits the distribution of many
      drugs in the brain. To this end, the exposure to the P-gp substrate quinidine was
      determined in the plasma and brain tissue after intravenous administration in
      rats at six different time points over the 24-h period. Our results indicate that
      time of administration significantly affects the exposure to quinidine in the
      brain. Upon inhibition of P-gp, exposure to quinidine in brain tissue is constant
      over the 24-h period. To gain more insight into processes regulating brain
      concentrations, we used intracerebral microdialysis to determine the
      concentration of quinidine in brain extracellular fluid (ECF) and cerebrospinal
      fluid (CSF) after intravenous administration at two different time points. The
      data were analyzed by physiologically based pharmacokinetic modeling using
      NONMEM. The model shows that the variation is due to higher activity of P-gp
      mediated transport from the deep brain compartment to the plasma compartment
      during the active period. Furthermore, the analysis reveals that CSF flux is
      higher in the resting period compared to the active period. In conclusion, we
      show that the exposure to a P-gp substrate in the brain depends on time of
      administration, thereby providing a new strategy for drug targeting to the brain.

PMID- 24917181
TI  - Assessment of baicalin in mouse blood by monoclonal antibody-based icELISA.
AB  - An indirect competitive enzyme-linked immunosorbent assay (icELISA) based on
      monoclonal antibaodies (MAb) was recently developed. This new method displays
      high sensitivity and accuracy, and is especially suitable for pharmacokinetic
      studies in small laboratory animals. This study aimed to develop an icELISA
      procedure for baicalin (BAL) quantitation in blood. We successfully developed the
      icELISA and applied in pharmacokinetic assays of Gegen Qinlian Decoction in mice.
      A linear correlation was obtained for BAL concentrations in the range from 34.69
      to 2220.00 ug/L. The regression equation was y = 1.5557 - 0.4028log(C) with a
      correlation coefficient of 0.9936. Precision and accuracy of the icELISA method
      were evaluated by the variations between replicates from well to well (intra
      assay) and plate to plate (inter-assay). The values obtained for these parameters
      were within the normal range (<15%). The recovery rates ranged from 98.93 to
      126.78%, meeting the requirements for biological samples. Stability studies
      showed that BAL sample solutions were intact for 1 h, enough time for UV
      detection. However, long-term storage and especially freeze-thaw procedures were
      detrimental to BAL. The pharmacokinetic parameters derived from mouse experiments
      were as follows: area under the curves from time 0 to 48 h, 1876.15 +/- 1108.14
      mg h/L; mean maximum blood concentrations, 101.09 +/- 31.53 mg/L; time of maximum
      concentration, 3.58 +/- 2.88 h; mean residence time, 79.30 +/- 61.21 h.

PMID- 24917182
TI  - The colorectal cancer screening process in community settings: a conceptual model
      for the population-based research optimizing screening through personalized
      regimens consortium.
AB  - Reducing colorectal cancer mortality by promoting screening has been a national
      goal for two decades. The NCI's Population-Based Research Optimizing Screening
      through Personalized Regimens (PROSPR) consortium is the first federal initiative
      to foster coordinated, transdisciplinary research evaluating the entire cancer
      screening process in community settings. PROSPR is creating a central data
      repository to facilitate research evaluating the breast, cervical, and colorectal
      cancer screening process across different patient populations, provider types,
      and delivery systems. Data are being collected and organized at the multiple
      levels in which individuals are nested (e.g., healthcare systems, facilities,
      providers, and patients). Here, we describe a conceptual model of the colorectal
      cancer screening process guiding data collection and highlight critical research
      questions that will be addressed through pooled data. We also describe the three
      research centers focused on colorectal cancer screening with respect to study
      populations, practice settings, and screening policies. PROSPR comprehensively
      elucidates the complex screening process through observational study, and has
      potential to improve care delivery beyond the healthcare systems studied.
      Findings will inform intervention designs and policies to optimize colorectal
      cancer screening delivery and advance the Institute of Medicine's goals of
      effective, efficient, coordinated, timely, and safe health care with respect to
      evidence-based cancer screening.

PMID- 24917183
TI  - Prediagnostic intake of dairy products and dietary calcium and colorectal cancer
      survival--results from the EPIC cohort study.
AB  - BACKGROUND: We investigated whether prediagnostic reported intake of dairy
      products and dietary calcium is associated with colorectal cancer survival.
      METHODS: Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at
      diagnosis, 64.2 +/- 8.1 years) in the European Investigation into Cancer and
      Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was
      assessed at baseline (1992-2000) using validated, country-specific dietary
      questionnaires. Multivariable Cox regression models were used to calculate HR and
      corresponding 95% confidence intervals (CI) for colorectal cancer-specific death
      (n = 1,028) and all-cause death (n = 1,525) for different quartiles of intake.
      RESULTS: The consumption of total dairy products was not statistically
      significantly associated with risk of colorectal cancer-specific death (adjusted
      HR Q4 vs. Q1, 1.17; 95% CI, 0.97-1.43) nor that of all-cause death (Q4 vs. Q1,
      1.16; 95% CI, 0.98-1.36). Multivariable-adjusted HRs for colorectal cancer
      specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99-1.48) for milk, 1.09 (95% CI,
      0.88-1.34) for yoghurt, and 0.93 (95% CI, 0.76-1.14) for cheese. The intake of
      dietary calcium was not associated with the risk of colorectal cancer-specific
      death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81-1.26) nor that of all-cause
      death (Q4 vs. Q1, 1.01; 95% CI, 0.84-1.21). CONCLUSIONS: The prediagnostic
      reported intake of dairy products and dietary calcium is not associated with
      disease-specific or all-cause risk of death in patients diagnosed with colorectal
      cancer. IMPACT: The impact of diet on cancer survival is largely unknown. This
      study shows that despite its inverse association with colorectal cancer risk, the
      prediagnostic intake of dairy and dietary calcium does not affect colorectal
      cancer survival.

PMID- 24917184
TI  - Inflammatory biomarker C-reactive protein and radiotherapy-induced early adverse
      skin reactions in patients with breast cancer.
AB  - BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the second
      leading cause of cancer death in American women. Postsurgery adjuvant
      radiotherapy (RT) significantly reduced the local recurrence rate. However, many
      patients develop early adverse skin reactions (EASR) that impact quality of life
      and treatment outcomes. METHODS: We evaluated an inflammatory biomarker, C
      reactive protein (CRP), in predicting RT-induced EASRs in 159 patients with
      breast cancer undergoing RT. In each patient, we measured pre- and post-RT plasma
      CRP levels using a highly sensitive ELISA CRP assay. RT-induced EASRs were
      assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity
      Criteria (v3.0). Associations between EASRs and CRP levels were assessed using
      logistic regression models after adjusting for potential confounders. RESULTS: RT
      induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3
      and 6 (end of RT), respectively. At the end of RT, a significantly higher
      proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in
      others); grade 2+ EASRs were significantly associated with: change of CRP > 1
      mg/L [odds ratio (OR), 2.51; 95% confidence interval (CI), 1.06-5.95; P = 0.04],
      obesity (OR, 2.08; 95% CI, 1.03-4.21; P = 0.04), or combined both factors (OR,
      5.21; 95% CI, 1.77-15.38; P = 0.003). CONCLUSION: This is the first study to
      demonstrate that an inflammatory biomarker CRP is associated with RT-induced
      EASRs, particularly combined with obesity. IMPACT: Future larger studies are
      warranted to validate our findings and facilitate the discovery and development
      of anti-inflammatory agents to protect normal tissue from RT-induced adverse
      effects and improve quality of life in patients with breast cancer undergoing RT.

PMID- 24917185
TI  - Effect of automated drug distribution systems on medication error rates in a
      short-stay geriatric unit.
AB  - RATIONALE, AIMS AND OBJECTIVES: To assess the impact of an automated drug
      distribution system on medication errors (MEs). METHODS: Before-after
      observational study in a 40-bed short stay geriatric unit within a 1800 bed
      general hospital in Valenciennes, France. Researchers attended nurse medication
      administration rounds and compared administered to prescribed drugs, before and
      after the drug distribution system changed from a ward stock system (WSS) to a
      unit dose dispensing system (UDDS), integrating a unit dose dispensing robot and
      automated medication dispensing cabinet (AMDC). RESULTS: A total of 615
      opportunities of errors (OEs) were observed among 148 patients treated during the
      WSS period, and 783 OEs were observed among 166 patients treated during the UDDS
      period. ME [medication administration error (MAE)] rates were calculated and
      compared between the two periods. Secondary measures included type of errors,
      seriousness of errors and risk reduction for the patients. The implementation of
      an automated drug dispensing system resulted in a 53% reduction in MAEs. All
      error types were reduced in the UDDS period compared with the WSS period
      (P<0.001). Wrong dose and wrong drug errors were reduced by 79.1% (2.4% versus
      0.5%, P=0.005) and 93.7% (1.9% versus 0.01%, P=0.009), respectively. CONCLUSION:
      An automated UDDS combining a unit dose dispensing robot and AMDCs could reduce
      discrepancies between ordered and administered drugs, thus improving medication
      safety among the elderly.

PMID- 24917186
TI  - B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells.
AB  - BACKGROUND: B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc
      finger transcription factor, showed to be highly expressed in various human
      cancers in addition to malignancies in the lymphoid system. This study
      investigated the role of BCL6 expression in breast cancer and its clinical
      significance in breast cancer patients. METHODS: Expression of BCL6 protein was
      assessed using in situ hybridization and immunohistochemistry in 127 breast
      cancer patients and 50 patients with breast benign disease as well as in breast
      cell lines. Expression of BCL6 was restored or knocked down in two breast cancer
      cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The
      phenotypic change of these breast cancer cell lines was assessed using cell
      viability MTT, Transwell invasion, colony formation, and flow cytometry assays
      and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR
      were used to investigate the molecular events after manipulated BCL6 expression
      in breast cancer cells. RESULTS: BCL6 protein was highly expressed in breast
      cancer cell lines and tissue specimens and expression of BCL6 protein was
      associated with disease progression and poor survival of breast cancer patients.
      In vitro, the forced expression of BCL6 results in increased proliferation,
      anchorage-independent growth, migration, invasion and survival of breast cancer
      cell lines, whereas knockdown of BCL6 expression reduced these oncogenic
      properties of breast cancer cells. Moreover, forced expression of BCL6 increased
      tumor growth and invasiveness in a nude mouse xenograft model. At the gene level,
      BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of
      CXCR4 and cyclinD1 proteins. CONCLUSIONS: The current study demonstrated the
      oncogenic property of BCL6 in breast cancer and further study could target BCL6
      as a novel potential therapeutic strategy for breast cancer.

PMID- 24917188
TI  - Case-control study of occupational exposure to electric shocks and magnetic
      fields and mortality from amyotrophic lateral sclerosis in the US, 1991-1999.
AB  - We investigated the relationship between occupational exposure to electric shocks
      (ES) and magnetic fields (MF) and amyotrophic lateral sclerosis (ALS) using 1991
      1999 US mortality data. For each of the 5886 included ALS deaths, 10 controls
      matched on sex-, age-, year- and region-were selected from among other deaths.
      Usual occupation as reported on death certificates was linked to job-exposure
      matrices for ES and MF. Education and electric occupations were associated with
      moderately increased ALS risks (odds ratio (OR)=1.85, 95% confidence interval
      (CI)=1.67, 2.04; OR=1.23, 95% CI=1.04, 1.47, respectively). For ES, ALS mortality
      OR were 0.73 (95% CI=0.67, 0.79) for high and 0.90 (95% CI=0.84, 0.97) for medium
      exposure compared with low exposure. For MF, ALS ORs were 1.09 (95% CI=1.00,
      1.19) for high and 1.09 (95% CI=0.96, 1.23) for medium exposure as compared with
      low exposure. For electric occupations, ALS ORs were insensitive to adjustments
      for ES, MF or both. Consistent with previous publications, an association between
      electric occupations and ALS was observed. Findings do not support occupational
      exposure to ES or MF as an explanation. 

PMID- 24917189
TI  - Public, official, and industry submissions on a Bill to increase the alcohol
      minimum purchasing age: A critical analysis.
AB  - BACKGROUND: In 2005 a Bill was introduced to the New Zealand parliament to
      increase the alcohol minimum purchasing age (MPA) from 18 to 20 years and
      submissions were invited from interested parties. We sought to characterise and
      critique the arguments tendered for and against the proposal. METHODS: We used
      template analysis to study written submissions on the Bill from 178 people and
      organisations in New Zealand. Independent raters coded submissions according to
      the source, whether for or opposed, and the arguments employed. RESULTS: The most
      common sources of submissions were members of the public (28%), the alcohol
      industry (20%), and NGOs (20%). Overall, 40% opposed increasing the MPA, 40% were
      in favour, 4% supported a split MPA (18 years for on-premise, 20 years for off
      premise), 7% were equivocal, and 8% offered no comment. The most common
      proponents of increasing the MPA were NGOs (36%) and members of the public (30%)
      and their arguments concerned the expected positive effects on public health
      (36%) and public disorder/property damage (16%), while 24% argued that other
      strategies should be used as well. The most common sources of opposition to
      increasing the MPA were the alcohol industry (50%) and the public (20%). It was
      commonly claimed that the proposed law change would be ineffective in reducing
      harm (22%), that other strategies should be used instead (16%), that it would
      infringe adult rights (15%), and that licensed premises are safe environments for
      young people (14%). There were noteworthy examples of NGOs and government
      agencies opposing the law change. The alcohol industry maximised its impact via
      multiple submissions appealing to individual rights while neglecting to report or
      accurately characterise the scientific evidence. Several health and welfare
      agencies presented confused logic and/or were selective in their use of
      scientific evidence. CONCLUSION: In contrast to the fragmented and inconsistent
      response from government and NGOs, the alcohol industry was organised and united,
      with multiple submissions from the sector with most at stake, namely the
      hospitality industry, and supporting submissions from the manufacturing, import,
      and wholesale sectors. Systematic reviews of research evidence should be
      routinely undertaken to guide the legislature and submissions should be
      categorised on the basis of pecuniary interest.

PMID- 24917190
TI  - Monitoring novel psychoactive substances allegedly offered online for sale in
      Persian and Arabic languages.
AB  - BACKGROUND: Numbers of novel psychoactive substances (NPS) have been rapidly
      increasing over the past few years, with unprecedented challenges on traditional
      drug control systems. The web has been involved in the promotion and knowledge
      dissemination of NPS, which are being presented online as safer/legal
      alternatives to illicit drugs. The physical, psychological and social harms
      associated with NPS have been studied so far mainly in Europe and other English
      speaking countries. The aim of this research is to provide knowledge on the
      provision of NPS information/purchase opportunities to Middle East customers,
      whilst monitoring the Internet in Arabic and Farsi. METHODS: Web
      analysis/assessments were carried out in both Farsi and Arabic between 2011 and
      2013. Sources were scrutinized with the help of different search engines,
      including Google Arabic and Google Persian, to carry out searches focusing on
      both NPS retailers' and social network websites. RESULTS: The research identified
      45 NPS apparently offered for purchase online. Most of these products were of
      synthetic origin; a few herbal stimulants were identified as well. The pro drug
      websites were not here easily identified, being hidden behind other, unrelated,
      websites. CONCLUSION: Present results may constitute a public health challenge to
      be considered at both national and worldwide level. New legislative frameworks
      should also be encouraged in order to ensure a better response to the current
      threat posed by rapid emergence of these substances.

PMID- 24917187
TI  - Forms of momentum across space: representational, operational, and attentional.
AB  - Cognition can exhibit biases consistent with future expectations, and some of
      these biases result in momentum-like effects and have been linked with the idea
      of an internalization of the effects of momentum. These momentum-like effects
      include representational momentum, operational momentum, and attentional
      momentum. Similarities and differences between these different momentum-like
      effects are considered. Hubbard's (2005) review of representational momentum is
      updated to include studies published since that review appeared, and the first
      full reviews of operational momentum and attentional momentum are provided. It is
      suggested that (1) many variables that influence one of these momentum-like
      effects have a similar influence on another momentum-like effect, (2)
      representational momentum, operational momentum, and attentional momentum reflect
      similar or overlapping mechanisms, and operational momentum and attentional
      momentum are special cases of representational momentum, and (3) representational
      momentum, operational momentum, and attentional momentum reflect properties of a
      more general spatial representation in which change or transformation of a
      stimulus is mapped onto motion in a spatial coordinate system. 

PMID- 24917192
TI  - Judging the carcinogenicity of rare human papillomavirus types.

PMID- 24917191
TI  - Intractable duodenal ulcer caused by transmural migration of gossypiboma into the
      duodenum--a case report and literature review.
AB  - BACKGROUND: Gossypiboma is a term used to describe a mass that forms around a
      cotton sponge or abdominal compress accidentally left in a patient during
      surgery. Transmural migration of an intra-abdominal gossypiboma has been reported
      to occur in the digestive tract, bladder, vagina and diaphragm. Open surgery is
      the most common approach in the treatment of gossypiboma. However, gossypibomas
      can be extracted by endoscopy while migrating into the digestive tract. We report
      a case of intractable duodenal ulcer caused by transmural migration of
      gossypiboma successfully treated by duodenorrhaphy. A systemic literature review
      is provided and a scheme of the therapeutic approach is proposed. CASE
      PRESENTATION: A 61-year-old Han Chinese man presented with intermittent
      epigastric pain for the last 10 months. He had undergone laparoscopic
      cholecystectomy conversion to open cholecystectomy for acute gangrenous
      cholecystitis 10 months ago at another hospital. Transmural migration of
      gossypiboma into the duodenum was found. Endoscopic intervention failed to remove
      the entire gauze, and duodenal ulcer caused by the gauze persisted. Surgical
      intervention was performed and the gauze was removed successfully. The penetrated
      ulcer was repaired with duodenorrhaphy. The postoperative period was
      uneventful.We systematically reviewed the literature on transmural migration of
      gossypiboma into duodenum and present an overview of published cases. Our PubMed
      search yielded seven reports of transmural migration of retained surgical sponge
      into the duodenum. Surgical interventions were necessary in two patients.
      CONCLUSION: Transmural migration of gossypiboma into the duodenum is a rare
      surgical complication. The treatment strategies include endoscopic extraction and
      surgical intervention. Prompt surgical intervention should be considered for
      emergent conditions such as active bleeding, gastrointestinal obstruction, or
      intra-abdominal sepsis. For non-emergent conditions, surgical intervention could
      be considered for intractable cases in which endoscopic extraction failed.

PMID- 24917194
TI  - H2O 2 induces myocardial hypertrophy in H9c2 cells: a potential role of Ube3a.
AB  - Myocardial hypertrophy that often leads to eventual heart failure is a leading
      cause of mortality worldwide. While both apoptosis and cell proliferation have
      been reported to play an important part in heart failure, its exact triggering
      mechanism is still unclear. Reports have shown that low concentrations of H2O2
      (10-30 uM) can induce myocardial hypertrophy without affecting survival. The
      ubiquitin ligase Ube3a has been reported to have a close affiliation with
      Angelman syndrome; but many ubiquitin ligases have been reported in a variety of
      cardiovascular conditions including myocardial hypertrophy. However, the
      relationship between Ube3a and myocardial hypertrophy has never been reported in
      literature. The rat cardiac myoblast cell line H9c2 and primary neonatal
      cardiomyocytes showed similar hypertrophic responses in vitro. In this report, we
      utilized H2O2 treatment on H9c2 cells to induce myocardial hypertrophy and
      determined the relationship between Ube3a and myocardial hypertrophy. Our results
      showed that 10-20 MUM H2O2 can induce myocardial hypertrophy without affecting
      cell viability and inducing cell apoptosis, while the corresponding transcription
      and translation levels of Ube3a are significantly increased during the process.
      Therefore, these findings underline that Ube3a may play an important role in
      myocardial hypertrophy. 

PMID- 24917195
TI  - Prevention of alcohol-heightened aggression by CRF-R1 antagonists in mice:
      critical role for DRN-PFC serotonin pathway.
AB  - Alcohol can escalate aggressive behavior in a significant subgroup of rodents,
      humans, and nonhuman primates. The present study investigated whether blockade of
      corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the
      emergence of alcohol-heightened aggression in mice. The serotonin (5-HT) pathway
      from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF
      R1 was investigated as a possible target for the prevention of alcohol-heightened
      aggressive behavior. Male CFW mice that reliably exhibited aggressive behaviors
      after consuming 1 g/kg of alcohol received systemic or intra-DRN administration
      of CRF-R1 antagonists, CP-154,526 or MTIP, before a confrontation with a male
      conspecific. Blockade of DRN CRF-R1 receptors with both antagonists significantly
      reduced only alcohol-heightened aggression, whereas systemic administration
      reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A
      agonist, 8-OH-DPAT, was coadministered with CP-154,526 into the DRN to
      temporarily disrupt 5-HT activity. This manipulation abolished the antiaggressive
      effects of intra-DRN CP-154,526. In the mPFC, in vivo microdialysis revealed that
      extracellular 5-HT levels were increased in mice that consumed alcohol and were
      then injected with CP-154,526, both systemically or intra-DRN. Neither alcohol
      nor CP-154,526 alone affected 5-HT release in the mPFC. The present results
      suggest the DRN as a critical site for CRF-R1 to modulate alcohol-heightened
      aggression via action on the serotonergic DRN-PFC pathway. 

PMID- 24917196
TI  - Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial
      hardship to affect depression risk.
AB  - There is increasing evidence that genetic factors have a role in differential
      susceptibility to depression in response to severe or chronic adversity. Studies
      in animals suggest that nitric oxide (NO) signalling has a key role in depression
      like behavioural responses to stress. This study investigated whether genetic
      variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the
      relationship between psychosocial stress and current depression score. We
      recruited a population sample of 1222 individuals who provided DNA and
      questionnaire data on symptoms and stress. Scores on the List of Life-Threatening
      Experiences (LTE) questionnaire for the last year and self-rated current
      financial hardship were used as measures of recent/ongoing psychosocial stress.
      Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs,
      comprising two regional haplotypes, and current depression score were identified
      that survived correction for multiple testing when current financial hardship was
      used as the interaction term. A smaller three-SNP haplotypes (rs10507279,
      rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the
      strongest effects, with the A-C-T haplotype associating with higher depression
      scores at low adversity levels but lower depression scores at higher adversity
      levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure
      to economic and psychosocial stressors to alter individual's susceptibility to
      depression. 

PMID- 24917197
TI  - Impaired adrenergic-mediated plasticity of prefrontal cortical glutamate synapses
      in rats with developmental disruption of the ventral hippocampus.
AB  - Neonatal ventral hippocampus (nVH) lesion in rats is a useful model to study
      developmental origins of adult cognitive deficits and certain features of
      schizophrenia. nVH lesion-induced reorganization of excitatory and inhibitory
      neurotransmissions within prefrontal cortical (PFC) circuits is widely believed
      to be responsible for many of the behavioral abnormalities in these animals. Here
      we provide evidence that development of an aberrant medial PFC (mPFC) alpha-1
      adrenergic receptor (alpha-1AR) function following neonatal lesion markedly
      affects glutamatergic synaptic plasticity within PFC microcircuits and
      contributes to PFC-related behavior abnormalities. Using whole-cell patch-clamp
      recording, we report that norepinephrine-induced alpha-1AR-dependent long-term
      depression (LTD) in a subset of cortico-cortical glutamatergic inputs is
      strikingly diminished in mPFC slices from nVH-lesioned rats. The LTD impairment
      occurs in conjunction with completely blunted alpha-1AR signaling through
      extracellular signal-regulated kinase 1/2. These alpha-1AR abnormalities have
      functional significance in a mPFC-related function, that is, extinction of
      conditioned fear memory. Post-pubertal animals with nVH lesion show significant
      resistance to extinction of fear by repeated presentations of the conditioned
      tone stimulus. mPFC infusion of an alpha-1AR antagonist (benoxathian) or LTD
      blocking peptide (Tat-GluR23Y) impaired fear extinction in sham controls, but had
      no significant effect in the lesioned animals. The data suggest that impaired
      alpha-1 adrenergic regulation of cortical glutamatergic synaptic plasticity may
      be an important mechanism in cognitive dysfunctions reported in
      neurodevelopmental psychiatric disorders. 

PMID- 24917198
TI  - A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar
      depression.
AB  - Depression in bipolar disorder (BPD) is challenging to treat. Therefore,
      additional medication options are needed. In the current report, the effect of
      the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults
      (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated
      to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures
      included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of
      Depressive Symptomatology-Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety
      (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were
      assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA
      with a between factor of treatment assignment, a within factor (repeated) of
      visit, and the baseline value, as well as age and gender, as covariates. In
      participants with at least one postbaseline visit (n=73), a significant treatment
      by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was
      observed. Depression remission rates were greater in the pregnenolone group (61%)
      compared with the placebo group (37%), as assessed by the IDS-SR (chi(2)(1)=3.99,
      p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels
      were observed in the pregnenolone group but not in the placebo group. In the
      pregnenolone group, baseline-to-exit change in the HRSA correlated negatively
      with changes in allopregnanolone (r(22)=-0.43, p=0.036) and pregNANolone (r(22)=
      0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that
      pregnenolone may improve depressive symptoms in patients with BPD and can be
      safely administered. 

PMID- 24917199
TI  - Relationship between brain glutamate levels and clinical outcome in individuals
      at ultra high risk of psychosis.
AB  - Alterations in brain glutamate levels may be associated with psychosis risk, but
      the relationship to clinical outcome in at-risk individuals is unknown. Glutamate
      concentration was measured in the left thalamus and anterior cingulate cortex
      (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at
      ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of
      attenuated positive symptoms and overall functioning were assessed. Measures were
      repeated in 51 UHR and 33 Control subjects after a mean of 18 months. UHR
      subjects were allocated to either remission (no longer meeting UHR criteria) or
      non-remission (meeting UHR or psychosis criteria) status on follow-up assessment.
      Thalamic glutamate levels at presentation were lower in the UHR non-remission
      (N=29) compared with the remission group (N=22) (t(49)=3.03; P=0.004), and were
      associated with an increase in the severity of total positive symptoms over time
      (r=-0.33; df=47; P=0.02), most notably abnormal thought content (r=-0.442; df=47;
      P=0.003). In the UHR group, ACC glutamate levels were lower at follow-up compared
      with baseline (F(80)=4.28; P=0.04). These findings suggest that measures of brain
      glutamate function may be useful as predictors of clinical outcome in individuals
      at high risk of psychosis. 

PMID- 24917200
TI  - Early-life experience, epigenetics, and the developing brain.
AB  - Development is a dynamic process that involves interplay between genes and the
      environment. In mammals, the quality of the postnatal environment is shaped by
      parent-offspring interactions that promote growth and survival and can lead to
      divergent developmental trajectories with implications for later-life
      neurobiological and behavioral characteristics. Emerging evidence suggests that
      epigenetic factors (ie, DNA methylation, posttranslational histone modifications,
      and small non-coding RNAs) may have a critical role in these parental care
      effects. Although this evidence is drawn primarily from rodent studies, there is
      increasing support for these effects in humans. Through these molecular
      mechanisms, variation in risk of psychopathology may emerge, particularly as a
      consequence of early-life neglect and abuse. Here we will highlight evidence of
      dynamic epigenetic changes in the developing brain in response to variation in
      the quality of postnatal parent-offspring interactions. The recruitment of
      epigenetic pathways for the biological embedding of early-life experience may
      also have transgenerational consequences and we will describe and contrast two
      routes through which this transmission can occur: experience dependent vs
      germline inheritance. Finally, we will speculate regarding the future directions
      of epigenetic research and how it can help us gain a better understanding of the
      developmental origins of psychiatric dysfunction. 

PMID- 24917201
TI  - Improvement of the Rett syndrome phenotype in a MeCP2 mouse model upon treatment
      with levodopa and a dopa-decarboxylase inhibitor.
AB  - Rett Syndrome is a neurodevelopmental autism spectrum disorder caused by
      mutations in the gene coding for methyl CpG-binding protein (MeCP2). The disease
      is characterized by abnormal motor, respiratory, cognitive impairment, and
      autistic-like behaviors. No effective treatment of the disorder is available.
      Mecp2 knockout mice have a range of physiological and neurological abnormalities
      that resemble the human syndrome and can be used as a model to interrogate new
      therapies. Herein, we show that the combined administration of Levodopa and a
      Dopa-decarboxylase inhibitor in RTT mouse models is well tolerated, diminishes
      RTT-associated symptoms, and increases life span. The amelioration of RTT
      symptomatology is particularly significant in those features controlled by the
      dopaminergic pathway in the nigrostratium, such as mobility, tremor, and
      breathing. Most important, the improvement of the RTT phenotype upon use of the
      combined treatment is reflected at the cellular level by the development of
      neuronal dendritic growth. However, much work is required to extend the duration
      of the benefit of the described preclinical treatment. 

PMID- 24917202
TI  - Lipopolysaccharide reduces incentive motivation while boosting preference for
      high reward in mice.
AB  - Inflammation has been implicated in the development of various psychiatric
      disorders, including depression. However, the neurobehavioral mechanism involved
      in this relationship remains elusive. This gap in knowledge may best be filled by
      evaluating elementary neurobehavioral units affected by inflammation rather than
      behavioral changes in conventional animal tests of depression. To this end, the
      current study used a concurrent choice paradigm to evaluate inflammation-induced
      motivational changes. Male C57BL/6J mice (n=27) were food restricted to between
      85 and 90% of their free-feeding weight and were trained to perform a concurrent
      choice task where they nose-poked for grain rewards on a fixed ratio (FR) 1
      schedule (low effort/low reward) and chocolate-flavored rewards on a FR-10
      schedule (high effort/high reward). A counterbalanced-within subjects design was
      used. A single intraperitoneal injection of 0.33 mg/kg lipopolysaccharide (LPS)
      was used to induce peripheral inflammation. Twenty-four hours after LPS
      administration, mice showed a reduction in the total number of nose pokes. A
      proportionally greater reduction in nose pokes was observed for grain, resulting
      in an increase in percent chocolate pellets earned. These behavioral changes
      cannot be explained by reduced appetite as feeding before the test led to a
      similar increase in percent chocolate pellets earned but without any decrease in
      responding. These results indicate that inflammation modulates incentive
      motivation by affecting willingness to exert effort for reward and not by
      reducing sensitivity to reward. 

PMID- 24917203
TI  - Prevalence of enterotoxins and toxin gene profiles of Staphylococcus aureus
      isolates recovered from a bakery involved in a second staphylococcal food
      poisoning occurrence.
AB  - AIMS: The study objective was to characterize and analyse the distribution of
      enterotoxins and genes encoding enterotoxins in Staphylococcus aureus strains
      recovered from the 601 environment and ingredient samples obtained during
      multiple inspections of a bakery implicated in two separate staphylococcal food
      poisoning incidents. METHODS AND RESULTS: Staphylococcus aureus isolates were
      evaluated using serological assays for identification of classical staphylococcal
      enterotoxins (SEs) SEA-SEE and polymerase chain reaction for the detection of
      newly described SE and SE-like enterotoxin genes seg-seu. Pulsed field gel
      electrophoresis identified thirteen pattern types. During these investigations, a
      total of 585 environmental swabs and 16 raw ingredient samples were collected by
      investigators, 85 of which were confirmed to contain Staph. aureus; of those
      isolates, 95.3% (81/85) harboured enterotoxin genes and 4.7% (4/85) carried newly
      described SE and SE-like enterotoxin genes in the absence of classical
      enterotoxins. CONCLUSIONS: Our research demonstrates the prevalence and diversity
      of classical SEs and the probable underestimated impact of nonclassical SE and SE
      like enterotoxins role in domestic staphylococcal food poisoning outbreaks.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Given the abundance of SEs and SE-like
      toxins, these findings illustrate the utilization of PCR for enterotoxin gene
      identification and its significance in outbreak investigations.

PMID- 24917204
TI  - Left ventricular pseudoaneurysm after reimplantation procedure.
AB  - Postoperative left ventricular pseudoaneurysm is a rare, but potentially lethal,
      complication because of the high risk of rupture and high mortality of repair. We
      report a 64-year-old man with Marfan syndrome who underwent the reimplantation
      valve-sparing aortic root replacement complicated by a postoperative left
      ventricular pseudoaneurysm that required urgent repair. Careful handling of the
      aortic root is required to avoid a left ventricular pseudoaneurysm, particularly
      in patients with connective tissue disorder. 

PMID- 24917205
TI  - Feasibility of esophageal reconstruction using a pedicled jejunum with
      intrathoracic esophagojejunostomy in the upper mediastinum for esophageal cancer.
AB  - OBJECTIVE: An alternative conduit is needed when the gastric tube cannot be used
      as an esophageal substitute for reconstruction after esophagectomy. We adopted
      pedicle jejunal reconstruction with intrathoracic anastomosis in the upper
      mediastinum under such circumstances. The aim of this study was to evaluate the
      feasibility of this technique. METHODS: Two hundred and ten patients with
      esophageal cancer underwent esophagectomy and reconstruction from 1998 to 2013.
      Among them, 6 patients underwent colon interposition (colon group) and 13
      underwent jejunum reconstruction (jejunum group) including 8 thoracoscopic
      anastomosis. The operative results of both groups were compared with those of 191
      gastric tube reconstructions (stomach group). RESULTS: The operative times in the
      colon and jejunum groups were significantly longer than that in the stomach group
      (P = 0.001 and P = 0.018, respectively). The colon group showed more operative
      blood loss and more frequent anastomotic leakage and ischemic stenosis of the
      conduit than did the stomach group (1605 vs. 530 g, P = 0.007; 50 vs. 12.6 %, P =
      0.035; 16.7 vs. 0 %, P = 0.03, respectively). There was no anastomotic leakage,
      conduit necrosis and mortality in the jejunum group. Ischemic stenosis of the
      conduit occurred more frequently in jejunum group than in the stomach group (23.1
      vs. 0 %, P < 0.001). However, the stenosis could be managed safely with
      endoscopic treatment. Patient survival in the colon and jejunum groups was
      consistent with that in the stomach group. CONCLUSIONS: Pedicle jejunal
      reconstruction with intrathoracic anastomosis can be performed safely under
      thoracotomy or thoracoscopic surgery when stomach cannot be used as an esophageal
      substitute after esophagectomy.

PMID- 24917206
TI  - A model of immunohistochemical differences between invasive breast cancers and
      DCIS lesions tested on a consecutive case series of 1248 patients.
AB  - BACKGROUND: A previous theoretic model (Tumour Biol 2013;34:1-7.) that breast
      tumor types differ in the relative rate of tissue invasion was elaborated and
      developed on a consecutive case series. METHOD: Histologic data of 68 ductal
      breast cancer in situ (DCIS) and 1180 invasive ductal cancer (IDC) patients were
      collected and analyzed. RESULTS: ER+PgR- phenotype was more common in Luminal B2
      than among the pooled Luminal A&B1 (p = 0.0002), and more frequent in Luminal B1
      than in Luminal A (p = 0.0167). The same phenotype was associated with the age
      older than 54 years in Luminal B1 and in B2 patients. HER2 type cancers were more
      frequent in older patients (p = 0.0038).Tumor progression from DCIS to IDC was
      found 39% faster than the average in Luminal B1 tumors, supporting the clinical
      importance of this tumor type. A rare combination of low Ki-67 in HER2 type
      cancers (only 14% of HER2 type cancers) showed very slow transition to IDC
      (occurring at only 53.55% of average progression rate), while triple-negative
      cancers progressed faster than the average, despite Ki-67 value (104.63% for low
      and 114.27% for high Ki-67 tumors).In three tumor types with positive steroid
      receptors the ER+PgR- phenotype showed slower IDC transition than the ER+PgR+
      phenotype of the same tumor type (difference in progression rate was 38% for
      Luminal A, 46% for Luminal B1 and 67% for Luminal B2 with Ki67 > 14%).Triple
      negative tumors in younger patients exceeded the expected average progression
      rate by 24%, while in HER2 type tumors, the rate of tissue invasion was in
      younger patients 20% lower than the expected value. CONCLUSIONS: The relative
      rate of tissue invasion differed substantialy among our patients. Differences
      depended on tumor types, steroid expression phenotypes and age. The dysfunctional
      ERs in the ER+PgR- phenotype showed slower rates of tissue invasion, suggesting
      that ligand binding to functional breast tumor ERs, beside promoting the PgR
      expression, possibly also promotes tumor transition to the invasive phase.In
      triple-negative tumors, an age dependent premenopausal mechanism possibly acted
      as an accelerator of tissue invasion, while faster tissue invasion by HER2
      overexpressed tumors in older patients possibly depended on an unidentified
      mechanism that takes more time to be acquired, so it was less present in
      premenopausal patients.

PMID- 24917207
TI  - Invasion of Solanum tuberosum L. by Aspergillus terreus: a microscopic and
      proteomics insight on pathogenicity.
AB  - BACKGROUND: Aspergillus terreus is one of the most harmful filamentous fungal
      pathogen of humans, animals and plants. Recently, researchers have discovered
      that A. terreus can cause foliar blight disease in potato (Solanum tuberosum L.).
      We used light and scanning electron microscopy, and performed proteomics analysis
      in an attempt to dissect the invasion process of A. terreus in this important
      crop. RESULTS: Microscopic study revealed that invasion of leaf tissue is marked
      by rapid germination of A. terreus phialidic conidia (PC) by 4 h after
      inoculation. By 8 h after inoculation, primary germ tubes from PC differentiated
      into irregular protuberance, often displayed stomata atropism, and failed to
      penetrate via the epidermal cells. Colonization of leaf tissues was associated
      with high rate of production of accessory conidia (AC). These analyses showed the
      occurrence of a unique opposing pattern of AC, tissue-specific and produced on
      melanized colonizing hyphae during the infection of leaf tissue. A significant
      proteome change hallmarked by differential expression of class I patatin,
      lipoxygenase, catalase-peroxidase complex, and cysteine proteinase inhibitor were
      observed during tuber colonization. These proteins are often involved in signal
      transduction pathways and crosstalk in pathogenic responses. CONCLUSION: A.
      terreus abundantly produced AC and multipolar germinating PC to invade potato
      leaf tissue. Additionally, A. terreus differentially induced enzymes in potato
      tuber during colonization which facilitates rapid disease development.

PMID- 24917208
TI  - Immune responses of whiteleg shrimp, Litopenaeus vannamei (Boone, 1931), to
      bacterially expressed dsRNA specific to VP28 gene of white spot syndrome virus.
AB  - In this study, dsRNA specific to VP28 gene of white spot syndrome virus (WSSV) of
      shrimp was synthesized in Escherichia coli in large scale and studied the immune
      response of shrimp to dsRNA-VP28. The haematological parameters such as clotting
      time and total haemocytes counts, and immunological parameters such as
      prophenoloxidase (proPO), superoxide dismutase (SOD), superoxide anion (SOA) and
      malondialdehyde content, as well as the mRNA expression of ten immune-related
      genes were examined to estimate the effect of dsRNA-VP28 on the innate immunity
      of Litopenaeus vannamei. The activities of proPO, SOA and SOD significantly
      increased in haemocyte after dsRNA-VP28 treatment, whereas MDA content did not
      change significantly. Among the ten immune-related genes examined, only the mRNA
      expression of proPO, cMnSOD, haemocyanin, crustin, BGBP, lipopolysaccharides
      (LPs), lectin and lysozyme in haemocytes, gill and hepatopancreas of L. vannamei,
      was significantly upregulated at 12 h after dsRNA-VP28 treatment, while no
      significant expression changes were observed in Toll receptor and tumour receptor
      genes. The increase of proPO and SOD activities, and SOA level and mRNA
      expression level of proPO, cMnSOD, haemocyanin, crustin, BGBP, LPs, lectin and
      lysozyme after dsRNA-VP28 stimulation indicate that these immune-related genes
      were involved in dsRNA-VP28-induced innate immunity in shrimp. 

PMID- 24917210
TI  - Syndesmosis screws: how many, what diameter, where and should they be removed? A
      literature review.
AB  - Although screw fixation remains the most commonly used method of syndesmosis
      fixation, the ideal screw size, placement, and number remain controversial. In
      addition, there has been debate as to whether the screw should always be removed,
      and a number of studies have looked at radiological and functional outcomes. In
      addition a number of cadaveric models have been developed, but the correlation
      between cadaveric findings and functional outcomes remains unclear. This
      systematic review of the literature aims to summarise the available evidence on
      how many screws should be placed, of what diameter, through how many cortices, at
      what level, and whether they should be removed. 

PMID- 24917209
TI  - The cubital tunnel: a radiologic and histotopographic study.
AB  - Entrapment of the ulnar nerve at the elbow is the second most common compression
      neuropathy in the upper limb. The present study evaluates the anatomy of the
      cubital tunnel. Eighteen upper limbs were analysed in unembalmed cadavers using
      ultrasound examination in all cases, dissection in nine cases, and microscopic
      study in nine cases. In all cases, thickening of the fascia at the level of the
      tunnel was found at dissection. From the microscopic point of view, the ulnar
      nerve is a multifascicular trunk (mean area of 6.0 +/- 1.5 mm(2) ). The roof of
      the cubital tunnel showed the presence of superimposed layers, corresponding to
      fascial, tendineous and muscular layers, giving rise to a tri-laminar structure
      (mean thickness 523 +/- 235 MUm). This multilayered tissue was hyperechoic (mean
      thickness 0.9 +/- 0.3 mm) on ultrasound imaging. The roof of the cubital tunnel
      is elastic, formed by a myofascial trilaminar retinaculum. The pathological
      fusion of these three layers reduces gliding of the ulnar nerve during movements
      of the elbow joint. This may play a role in producing the symptoms typical of
      cubital tunnel syndrome. Independent from the surgical technique, decompression
      should span the ulnar nerve from the triceps brachii muscle to the flexor carpi
      ulnaris fascia. 

PMID- 24917211
TI  - Surgical resection of severe heterotopic ossification after open reduction and
      internal fixation of acetabular fractures: a case series of 18 patients.
AB  - OBJECTIVE: To evaluate the clinical results of surgical resection of severe
      heterotopic ossification (HO) after the open reduction and internal fixation
      (ORIF) of acetabular fractures. METHODS: A retrospective chart review was
      performed between October 2005 and November 2010 on patients undergoing severe HO
      resection following an acetabular fracture ORIF. Our primary outcome was
      functional status evaluated by the Harris hip score (HSS). HO resection and hip
      release was performed using a Kocher-Langenbeck approach in all cases, and a
      combined radiation and indomethacin regimen was used to prevent HO recurrence.
      Plain radiographs were also used to evaluate the hip joint for arthritic changes
      and HO recurrence. RESULTS: A total of 18 patients (17 males and 1 female) were
      included in our study analysis. The mean patient age was 36.8 (range: 22-54 years
      old) when HO resection surgery was performed. The mean time interval between
      acetabular fracture ORIF and HO resection was 9.9 months (range: 3-30 months): it
      was within 6 months in 7 patients, 6-12 months in 8 patients, and >12 months in 3
      patients. The HO was graded as Brooker grade III in 8 patients and grade IV in 10
      patients. The mean time interval between HO resection and the latest follow-up
      was 4.5 years (range: 2.1-7.8 years). The mean Harris hip score (HHS) was 84.5
      (range: 38-100), with a clinical outcome rating of excellent in 9 patients, good
      in 3 patients, fair in 4 patients, and poor in 2 patients (good and excellent
      rating accounted for 66.7%). The mean hip joint motion arc was 194 degrees 
      (range: 90-260 degrees ). Complications included one intraoperative femoral neck
      fracture, 1 sciatic nerve injury, 2 femoral head avascular necrosis, and 6 mild
      HO recurrences (33.3%). There was 28.6% recurrence if HO resection was within 6
      months and 36.4% if >6 months. There were no cases of severe HO recurrence, wound
      infections, deep vein thrombosis, or pulmonary embolism. CONCLUSION: The early
      surgical resection of severe HO after an acetabular fracture ORIF can provide
      satisfactory results, however the complication rate is relatively high.

PMID- 24917212
TI  - Covalent hypercoordination: can carbon bind five methyl ligands?
AB  - C(CH3)5(+) is the first reported example of a five-coordinate carbon atom bound
      only to separate (that is, monodentate) carbon ligands. This species illustrate
      the limits of carbon bonding, exhibiting Lewis-violating "electron-deficient
      bonds" between the hypercoordinate carbon and its methyl groups. Though not
      kinetically persistent under standard laboratory conditions, its dissociation
      activation barriers may permit C(CH3)5(+) fleeting existence near 0 K.

PMID- 24917213
TI  - Interaction between the SLC19A1 gene and maternal first trimester fever on
      offspring neural tube defects.
AB  - BACKGROUND: Many studies have indicated that the reduced folate carrier gene
      (SLC19A1) is associated with an increased risk of neural tube defects (NTDs).
      However, the interaction between the SLC19A1 gene variant and maternal fever
      exposure and NTD risk remains unknown. The aim of this study was to investigate
      whether the risk for NTDs was influenced by the interactions between the SLC19A1
      (rs1051266) variant and maternal first trimester fever. METHODS: We investigated
      the potential interaction between maternal first trimester fever and maternal or
      offspring SLC19A1 polymorphism through a population-based case-control study. One
      hundred and four nuclear families with NTDs and 100 control families with nonmal
      newborns were included in the study. SLC19A1 polymorphism was determined using
      polymerase chain reaction-restricted fragment length polymorphism. RESULTS:
      Mothers who had the GG/GA genotype and first trimester fever had an elevated risk
      of NTDs (adjusted odds ratio, 11.73; 95% confidence interval, 3.02-45.58) as
      compared to absence of maternal first trimester fever and AA genotype after
      adjusting for maternal education, paternal education, and age, and had a
      significant interactive coefficient (gamma = 3.17) between maternal GG/GA
      genotype and first trimester fever. However, there was no interaction between
      offspring's GG/GA genotype and maternal first trimester fever (the interactive
      coefficient gamma = 0.97) after adjusting for confounding factors. CONCLUSION:
      Our findings suggested that the risk of NTDs was potentially influenced by a gene
      environment interaction between maternal SLC19A1 rs1051266 GG/GA genotype and
      first trimester fever. Maternal GG/GA genotype may strengthen the effect of
      maternal fever exposure on NTD risk in this Chinese population.

PMID- 24917214
TI  - Life satisfaction and its correlates among older cancer survivors: critical role
      of psychosocial factors.

PMID- 24917215
TI  - The role of subcutaneous infusion of apomorphine in Parkinson's disease.
AB  - Continuous subcutaneous apomorphine infusion therapy (CSAI) has proved to be
      effective in advanced Parkinson's Disease patients with motor fluctuations not
      controlled by oral or transdermal medication. In this clinical setting it
      competes directly with intrajejunal levodopa and deep brain stimulation (DBS),
      however randomised controlled comparative studies are lacking. The advantages of
      CSAI is that it is the least invasive of these three therapeutic options, is
      reversible, practical to use and has shown significant efficacy for the
      management of both peak-effect dyskinesias and off-period nonmotor-symptoms.
      Contraindications to the use of CSAI are severe dementia or neuropsychiatric
      symptoms and severe biphasic dyskinesias, however unlike DBS, advanced age is not
      a contraindication. This review summarises the evidence regarding efficacy,
      safety and tolerability of CSAI, provides guidance on the selection of suitable
      patients and gives practical instructions on how to initiate CSAI and manage
      possible adverse events. 

PMID- 24917216
TI  - One-year mortality in elderly adults with non-ST-elevation acute coronary
      syndrome: effect of diabetic status and admission hyperglycemia.
AB  - OBJECTIVES: To determine whether type 2 diabetes mellitus and hyperglycemia on
      admission should be considered independent predictors of mortality in elderly
      adults with acute coronary syndrome (ACS). DESIGN: Prospective cohort study.
      SETTING: Twenty-three hospitals in Italy. PARTICIPANTS: Individuals aged 75 and
      older with non-ST-elevation ACS (NSTEACS) (mean age 82, 47% female) (N = 645).
      MEASUREMENTS: Diabetic status and blood glucose levels were assessed on
      admission. Hyperglycemia was defined as glucose greater than 140 mg/dL.
      Multivariable Cox proportional hazard regression was used to assess the potential
      confounding effect of major covariates on the association between diabetic
      status, admission glucose, and 1-year mortality. RESULTS: A history of diabetes
      mellitus was found in 231 participants (35.8%), whereas 257 (39.8%) had
      hyperglycemia. Hyperglycemia was found in 171 participants with diabetes mellitus
      (70%) and 86 (21%) without diabetes mellitus. Participants with diabetes mellitus
      were significantly (P < .05) more likely to have had prior myocardial infarction
      and stroke and had lower ejection fraction and blood hemoglobin. Hyperglycemia
      was associated with lower (P < .05) ejection fraction and estimated glomerular
      filtration rate (eGFR). Diabetic status and hyperglycemia were associated with
      greater 1-year mortality according to univariate analysis (54 participants with
      diabetes mellitus died (23.4%), versus 66 (15.9%) without diabetes mellitus
      (hazard ratio (HR) = 1.5 95% confidence interval (CI) = 1.0-2.1), and 60
      participants with hyperglycemia died (23.3%), versus 60 (15.5%) without
      hyperglycemia (HR=1.6; 95% CI = 1.1-2.2), but this association was not
      statistically significant after adjustment for ejection fraction, age, blood
      hemoglobin, and eGFR. CONCLUSION: In elderly adults with NSTEACS, diabetes
      mellitus and hyperglycemia on admission are associated with higher mortality,
      mostly because of preexisting cardiovascular and renal damage.

PMID- 24917217
TI  - Clozapine-induced blood dyscrasias in Saudi Arab patients.
AB  - BACKGROUND: Clozapine has shown superior efficacy over other antipsychotics.
      However, its use is complicated by the development of life-threatening
      hematologic adverse effects. OBJECTIVES: This paper reports the incidence of
      clozapine-induced hematologic toxicity in Saudi Arab patients. SETTING: King
      Khalid University Hospital, Riyadh, Saudi Arabia. METHODS: Medical data of Saudi
      Arab hospitalized patients receiving clozapine was retrospectively reviewed
      during the period between August 2009 and August 2012. White blood cell (WBC)
      counts and differentials were recorded in a specific form to watch for any
      hematologic toxicity. The hematologic toxicities included in this report are:
      eosinophilia, thrombocytopenia, lymphocytopenia, and
      agranulocytosis/neutropenia/leukopenia combined. MAIN OUTCOME MEASURE: Complete
      WBC count. RESULTS: During the study period 147 charts were reviewed. The mean
      age of patients was 38 +/- 11.42 years and 52 % were males. During the study
      period 61 patients (42 %) developed 82 blood dyscrasias. Sixteen patients (10.9
      %) developed agranulocytosis, neutropenia and leukopenia combined, while nineteen
      patients (12.9 %) developed lymphocytopenia, and seven patients (4.8 %) developed
      thrombocytopenia. Eosinophilia developed in 40 patients (27.2 %). During the
      first 18 weeks of therapy with clozapine, 21 (26 %) hematologic side effects were
      developed. CONCLUSION: The data collected in this study does appear to indicate
      there may be an increased incidence of blood dyscrasias in Saudi Arabs which
      warrants further, more detailed, study. It would be of concern to psychiatric
      clinicians if the case of a genetic predisposition to clozapine-induced blood
      dyscrasias were proven in the future.

PMID- 24917218
TI  - Patient characteristics among users of analgesic over-the-counter aspirin in a
      Danish pharmacy setting.
AB  - BACKGROUND: Use of over-the-counter (OTC) high-dose acetylsalicylic acid (ASA) is
      a risk factor for experiencing gastric bleeding. However, more detailed knowledge
      on the characteristics of users of OTC ASA is needed. OBJECTIVE: To characterise
      users of OTC high-dose ASA in a Danish pharmacy setting. METHOD: We conducted an
      interview based survey among users of OTC high-dose ASA. Questions were asked
      regarding: (1) demographic characteristics; (2) use patterns; (3) knowledge about
      adverse events; (4) risk factors for experiencing gastric bleeding; (5) reasons
      for choosing an ASA-containing medicine; and (6) whether their GP was informed on
      their use of high-dose ASA. RESULTS: One-hundred-seventeen interviews were
      completed. Nineteen percent and 37 % used high-dose ASA on a daily or weekly
      basis respectively. Sixty-eighth percent found high-dose ASA to be more effective
      than other analgesics. Fourty-seven percent had one or more risk factors for
      experiencing ulcer bleeding, most commonly age >60 years (32 %) and previous
      peptic ulcer (9 %). The most well-known adverse events were abdominal pain (32 %)
      and peptic ulcer (26 %). The most common source of information was friends and
      family (32 %). CONCLUSION: A large proportion of users of high-dose ASA have risk
      factors for experiencing gastric bleeding. Health-care professionals needs to
      provide more information on potential adverse events.

PMID- 24917219
TI  - A novel gene-protein assay for evaluating HER2 status in gastric cancer:
      simultaneous analyses of HER2 protein overexpression and gene amplification
      reveal intratumoral heterogeneity.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) protein
      overexpression and gene amplification are important biomarkers for trastuzumab
      treatment in breast and gastric cancer patients. Gastric cancer presents high
      rates of tumor heterogeneity, which may influence the results of HER2 testing. A
      novel gene-protein assay (GPA) can allow the simultaneous analysis of HER2
      protein and gene status on a single slide. METHODS: Using the tissue microarray
      technique, the HER2 status of each of 875 gastric cancer cases was evaluated by
      immunohistochemistry (IHC), brightfield dual-color in situ hybridization (DISH),
      and GPA. Intratumoral phenotypic and genotypic heterogeneity were evaluated by
      comparing the HER2 statuses of two tissue cores from each case. RESULTS: There
      was excellent concordance between GPA and IHC (99.2 %), as well as between GPA
      and DISH results (99.3 %). HER2 positivity obtained by GPA was almost identical
      (99.8 %) to the results obtained by IHC and DISH assays. Intratumoral phenotypic
      heterogeneity was more frequently observed in IHC 2+ cases (63.5 %) compared with
      IHC 3+ cases (28.3 %). Phenotypic heterogeneity (48.8 %) was more frequently
      observed than genotypic heterogeneity (26.8 %). Tumor heterogeneity was
      consistently observed from early to advanced stages. CONCLUSIONS: HER2-positive
      gastric cancers presented different levels of HER2 protein expression and gene
      amplification statuses within the same lesion in almost half the cases examined.
      Evaluating both phenotypic and genotypic heterogeneity may contribute to a deeper
      understanding and improved prediction of clinical outcome in gastric cancer
      patients treated with trastuzumab. This newly established GPA technology may also
      be useful for developing biomarkers for other molecularly targeted therapies.

PMID- 24917220
TI  - Mind over matter? The role of individual perceptions in understanding the social
      ecology of housing environments for individuals with psychiatric disabilities.
AB  - There is a disagreement in place-based research regarding whether objective
      indicators or individual perceptions of environments are better predictors of
      well-being. This study assessed environmental influences on well-being for 373
      individuals with psychiatric disabilities living independently in 66
      neighborhoods in the southeastern United States. Three questions were examined
      utilizing random effects models: (1) How much variance in personal and
      neighborhood well-being can be explained by neighborhood membership? (2) What is
      the relationship between participant perceptions of neighborhood quality and
      researcher ratings of neighborhood quality? and (3) What is the relative
      influence of individual perceptions, perceptions aggregated by neighborhood, and
      researcher ratings of neighborhood quality in predicting personal and
      neighborhood well-being? Results indicate that individual perceptions of
      neighborhood quality were more closely related to well-being than either
      aggregated perceptions or researcher ratings. Thus, participants' perceptions of
      their neighborhoods were more important indicators of their well-being than
      objective ratings made by researchers. Findings have implications for measurement
      approaches and intervention design in placed-based research.

PMID- 24917221
TI  - Specialized operating room for cesarean section in the perinatal care unit: a
      review of the opening process and operating room management.
AB  - We have opened an operating room in the perinatal care unit (PNCU), separate from
      our existing central operating rooms, to be used exclusively for cesarean
      sections. The purpose is to meet the increasing need for both emergency cesarean
      sections and non-obstetric surgeries. It is equipped with the same surgical
      instruments, anesthesia machine, monitoring system, rapid infusion system and
      airway devices as the central operating rooms. An anesthesiologist and a nurse
      from the central operating rooms trained the nurses working in the new operating
      room, and discussed solutions to numerous problems that arose before and after
      its opening. Currently most of the elective and emergency cesarean sections
      carried out during the daytime on weekdays are performed in the PNCU operating
      room. A total of 328 and 347 cesarean sections were performed in our hospital
      during 2011 and 2012, respectively, of which 192 (55.5 %) and 254 (73.2 %) were
      performed in the PNCU operating room. The mean occupancy rate of the central
      operating rooms also increased from 81 % in 2011 to 90 % in 2012. The PNCU
      operating room was built with the support of motivated personnel and
      multidisciplinary teamwork, and has been found to be beneficial for both surgeons
      and anesthesiologists, while it also contributes to hospital revenue.

PMID- 24917222
TI  - Reply to the comments on "impact of a new respiratory amplitude-based gating
      technique in evaluation of upper abdominal PET lesions".

PMID- 24917223
TI  - Diagnostic accuracy of FDG PET/CT in mediastinal lymph nodes from lung cancer.

PMID- 24917225
TI  - Editorial.

PMID- 24917226
TI  - Enuresis in childhood and premature ejaculation in adult life: An enigmatic
      similarity.
AB  - Abstract Objective. To investigate a possible association between enuresis in
      childhood and premature ejaculation in adult life. Methods. The authors conducted
      a retrospective study, with two cohorts, consisting of 60 men with premature
      ejaculation, and 60 comparison subjects who were asked to assess their enuresis
      in childhood, a history of psychological problems. Results. While 20 (33.3%)
      subjects with premature ejaculation reported a history of enuresis in childhood,
      only seven (11.6%) subjects without premature ejaculation had this problem in
      childhood. Enuresis in childhood was significantly more common in men with a
      premature ejaculation than controls. While 35 (58.3%) patients with premature
      ejaculation reported a history of psychological problems, only four (6.6%)
      controls reported this kind of problems. There was a significant difference
      between these groups regarding psychological problems. Conclusion. The results of
      this study suggest that the history of enuresis in childhood seems to increase
      the risk of having premature ejaculation and psychological problems in adult
      life. These results lead to a premise that these disorders may share a common
      etiology and/or neurological pathophysiology. 

PMID- 24917227
TI  - An association between month of birth and method of suicide.
AB  - Abstract Background. A statistically significant association between season of
      birth and suicidal behaviour has been reported. However, the effect of month of
      birth on the choice of suicide method is yet to be established. Aim. This study
      examines the association between commonly used methods of suicide and season of
      birth using data on suicide collected over a 21-year period in England, Wales and
      Scotland. The sample size available, in excess of 52,000 suicides, greatly
      exceeds all previous studies in this field. Method. Data on suicides registered
      between 1979 and 2000(r) were obtained from the Office for National Statistics
      (ONS) for England and Wales, and the General Register Office (GRO) for Scotland.
      Our analyses include all suicides [ICD 9 codes; E950- E959] and undetermined
      injury deaths [E980-E989], reported between 1979 and 2000 in England, Wales and
      Scotland for persons born between 1941 and 1966. We used Poisson and negative
      binomial generalised linear models (GLMs) with seasonal harmonic components.
      Results. Adjusting for the year of birth, the model predicts that the average
      increase in risk of suicide between the trough (October) and the peak (May) of
      the seasonal component is 17.9% (95% CI= 13-33%). For males the estimated
      increase in risk was 15% (95% CI 5-22%) and for females 27% (95% CI 8-47%). The
      effect of month of birth on suicide applied to all commonly used methods, with
      the exception of suicide by burning (SBB) with a significant increase of 16% (95%
      CI 2-37%) in people born in January compared to other methods. Conclusion. Our
      results replicate our earlier finding of an association between season of birth
      and suicide incidence. Birth rates of persons who kill themselves show a
      disproportionate excess in spring compared to other months. The unexpected
      observed finding in suicide by burning (SBB) may represent the effect of latitude
      and warrants further examination. Seasonality of birth in suicide may enhance our
      understanding of some biological aspects in its aetiology and give directions for
      future research. 

PMID- 24917228
TI  - Psychiatric morbidity in dermatological conditions.
AB  - Abstract Objective. A relationship between psychological factors and skin
      diseases has long been hypothesized. The objective of this study is to
      investigate the association of dermatology conditions with depression, anxiety
      and personality disorders. Method. A total of 144 dermatology outpatients and 100
      controls were selected and assessed by the Structured Clinical Interview for DSM
      III-R personality disorders and the Hospital Anxiety and Depression Scale for
      presence of personality disorders and anxiety and depression. Results. A total of
      77 (70%) of the patients and 26 (20%) of the control group reported moderate to
      severe anxiety and depression. Twenty-two patients (15.27%) and five controls
      (5%) suffered from personality disorders. Obsessive-compulsive personality
      disorder was the most diagnosed personality disorder followed by avoidant,
      borderline and dependent personalities. Conclusion. The association between
      dermatological diseases and psychiatric and personality morbidity underscores the
      deep emotional suffering that can be associated with skin diseases and confirms
      the importance of psychiatric evaluation of dermatology patients. Our findings
      highlight the need for a biopsychosocial approach to patients with skin disease. 

PMID- 24917229
TI  - Perceptions on efficacy and side effects of conventional depot antipsychotics
      (CDA) and atypical depot antipsychotics (ADA): Psychiatrists versus patients in
      Hong Kong.
AB  - Abstract Objectives. We compared the satisfaction level of psychiatrists and
      psychiatric patients towards conventional (CDA) and atypical (ADA) depot
      antipsychotics on symptom management, role functioning, and side effects. Method.
      Patients from an out-patient clinic of a public hospital and psychiatrists from
      public hospitals participated in the survey in 2007-2008. A total of 153 patients
      were interviewed by a tailor-made questionnaire and 72 psychiatrists self
      administered a similar questionnaire. Results. Both groups shared similar
      attitudes towards clinical effectiveness and treatment efficacy of ADA and CDA.
      More patients were ambivalent towards relapse prevention of CDA than
      psychiatrists (30.7 vs. 16.7%, P<0.044) and three quarters of psychiatrists
      believed that ADA are associated with less side effects. More than half of the
      patients showed negative attitudes towards the effectiveness of CDA on improving
      quality of life (52.40%), work (57.50%), and recreation (55.50%). Psychiatrists
      were more aware of the limitation of CDA and severity of side effects of CDA.
      They did not, however, seem to incorporate patients' opinions and research
      findings into their clinical practice. Conclusion. Evidence-based practice and
      shared decision-making model between clinicians and mental patients should be
      advocated. More investigations should be devoted to examine the efficacy of ADA
      as the alternative to CDA. 

PMID- 24917230
TI  - Cognitive function, social functioning and quality of life in first-episode
      psychosis: A 1-year longitudinal study.
AB  - Abstract Objective. The majority of patients with schizophrenia have cognitive
      deficits early in the disease. We evaluated the relationship between cognitive
      function, social functioning and quality of life in patients with first-episode
      psychosis. Methods. This was a longitudinal study in 15 patients aged 18-30 years
      who had recently experienced a first psychotic episode and were treated with the
      atypical antipsychotic aripiprazole, cognitive-behavioural therapy, psycho
      educational sessions, family supportive sessions and social interventions.
      Patients were evaluated at baseline and after 1 year. Cognitive assessment
      included attention, memory, language skills and problem solving. Social
      functioning, quality of life, and psychopathological evaluation were performed
      with validated tools. Results. At baseline, patients had a severe impairment of
      social functioning and a low quality of life, while a specific pattern of
      cognitive functions was not identified. After 1-year, we observed a significant
      improvement in social functioning and quality of life, without a significant
      decrease in cognitive function. Conclusion. Contrary to previous findings, we
      found that social functioning and quality of life are related, but independent of
      cognitive impairment. The use of antipsychotic agents that do not interefere with
      cognitive function plus psychological assistance is a valuable treatment approach
      in patients with first-episode schizophrenia. 

PMID- 24917231
TI  - Determination of clozapine in serum of patients with schizophrenia as a
      measurement of medication compliance.
AB  - Abstract Although antipsychotic drugs have been effective in reducing symptoms of
      schizophrenia, issues with adherence to these agents continue to be a barrier to
      the implementation and delivery of a successful treatment plan. An estimated 25%
      of patients with schizophrenia are partially adherent or non-adherent within 7-10
      days of beginning therapy. There are some ways to evaluate the pharmacotherapy
      adherence of the patients: evaluation of the disease symptoms and/or the side
      effects of the drugs, questionnaires to evaluate quality of life, patient
      attitude toward his (her) drugs and pill counts. Although these methods represent
      a good option, they are subjective; for example, if the patients lie this leads
      to false results. Drug monitoring of patients' biological fluids can be a useful
      tool to evaluate adherence by relating the serum or plasma levels of drugs with
      pharmacotherapy compliance. The aim of this study was to determine if serum
      clozapine levels are a suitable method for evaluating patient adherence to
      clozapine therapy. Clozapine concentration was determined in serum of 26
      volunteer patients who were using this drug as pharmacotheraphy for 6 months to 5
      years (steady state conditions at 7-10 days of treatment with the drug). The
      analysis was done for 6 months, with three samples taken for each patient during
      this time, relating clozapine serum concentration of lower than therapeutic range
      with pharmacotherapy non-adherence of patients. Moreover, we compared the
      evaluation of the pharmacotherapy adherence from serum levels of the drug, with
      the evaluation of the pharmacotherapy adherence from an indirect tool to evaluate
      symptoms of disease. Twelve patients were found non-adherent by clozapine serum
      concentration (46.15%), whereas eight patients were found non-adherent using
      clinician questionnaire (30.76%). After to evaluate some factors (cigarettes, co
      medication, inter-individual variability) that could give different results of
      adherence from evaluation of serum concentrations and from indirect methods, we
      can conclude that the clozapine serum concentration is a more objective method of
      evaluating pharmacotherapy adherence of patients receiving this drug. 

PMID- 24917232
TI  - Trends of benzodiazepine prescribing and the risk of hip fracture in elderly
      patients in Taiwan: A population-based study.
AB  - Abstract Objective. The aim of this study was to explore the trends of
      prescribing potentially inappropriate benzodiazepine use (PIBU) and the risk of
      fractures in an elderly population in Taiwan. Methods. Retrospective
      administrative database analysis was conducted. Outpatient claim data were
      retrieved from the Longitudinal Health Insurance Database (LHID) between 2000 and
      2003, which contains all inpatient and outpatient medical claims of approximately
      23 million patients in Taiwan. All patients with the diagnosis of hip fractures
      (ICD codes) were identified from the database. The inappropriate use for the
      elderly was defined as a prescription with the dose of short- and long-acting BZD
      according to the 2003 version of Beers' criteria. Multiple logistic regressions
      were used to determine the association of PIBU with fractures. Results. A total
      of 62,023 elderly patients aged ?65 years were retrieved from the database. The
      proportion of elderly patients taking short-and long-acting benzodiazepines
      declined significantly from 28.1 to 25% and 19.5 to 14.5% from 2000 to 2003,
      respectively (P<0.001). After adjustment for age, sex, co-morbidity, other
      medications in one prescription and all of the covariates, the risk of hip
      fractures (~50%) was still statistically significant (adjusted OR in the four
      years studied: 1.57, 1.38, 1.68, 1.45) for elderly patients taking
      benzodiazepines in Taiwan. Conclusion. These findings suggest that the
      inappropriate use of benzodiazepine may be associated with the risk of fractures.
      Physicians should prescribe benzodiazepines appropriately for the elderly to
      minimize the risk of hip fractures. 

PMID- 24917233
TI  - Long-term observation of patients successfully switched to risperidone long
      acting injectable: A retrospective, naturalistic 18-month mirror-image study of
      hospitalization rates and therapy costs.
AB  - Abstract Objective. The aim of the present 18-month retrospective study was to
      assess the association between a continuous long-term treatment with risperidone
      long-acting injectable (RLAI) of at least 12 months and in-patient care of
      patients suffering of schizophrenia or schizoaffective disorder. Furthermore we
      wanted to assess the cost-effectiveness of a long-term treatment with RLAI.
      Methods. In a mirror-image design, data of 119 patients with schizophrenia and
      schizoaffective disorder who were switched to RLAI treatment were analyzed
      retrospectively. Hospitalization rates, the duration of inpatient treatment and
      the overall treatment costs were assessed 12 and 18 months after switching to
      RLAI and compared to the equivalent time preceding the switch. Results. After 12
      and 18 months of RLAI treatment, the mean reduction of inpatient care was 27.4
      and 38.4 days per patient, respectively, compared to the equivalent time period
      prior to switching to RLAI (Wilcoxon P < 0.001). The overall savings in drug and
      institutional-care costs were 21.1 and 21.9%, respectively. Conclusions. Patients
      receiving RLAI for at least 12 months showed a reduction in inpatient days and
      lower overall treatment costs. 

PMID- 24917234
TI  - Mental health services utilization and driving violations.
AB  - Abstract Objective. The objective of this study was to determine whether there is
      a relationship between the past utilization of four mental health services (i.e.
      ever been seen by a psychiatrist, ever been in a psychiatric hospital, ever been
      in counseling, ever been on psychotropic medication) and different types of
      driving citations during one's lifetime. Methods. Using a consecutive, cross
      sectional, primary care sample, we surveyed participants about their past use of
      four mental health services and lifetime incidence of 29 different types of
      driving citations (charges, not convictions). Results. The total number of
      different types of moving violations was statistically significantly related to a
      history of psychiatric hospitalization. The total number of different types of
      non-moving violations was statistically significantly related to all mental
      health services variables. Conclusions. In this study, general non-specific
      queries about the past utilization of mental health services were correlated with
      both moving violations (past psychiatric hospitalization) and non-moving
      violations (all mental health services variables). These findings suggest that
      patients who have received mental health treatment are at a higher risk for being
      cited for driving violations than those who have not received mental health
      treatment. However, among the mental health variables under study, only past
      psychiatric hospitalization was associated with moving violations. 

PMID- 24917235
TI  - Efficacy of milnacipran in the treatment of chronic pain syndromes.
AB  - Abstract Eleven outpatients with chronic pain syndromes other than fibromyalgia
      were treated for 12 weeks with milnacipran, a novel serotonin noradrenaline
      reuptake inhibitor. The agent was administered at 50-150 mg/day, and the mean +/-
      SD dose at 12 weeks or at the time drug treatment was stopped was 84.1 +/- 32.2
      mg/day. None of the patients met the DSM-IV criteria for a major depressive
      disorder. Abdominal, chest, back, arm, leg or glossal pain, or headache was
      involved. Pain was assessed clinically by means of a visual analog scale (VAS)
      before and 12 weeks after the start of milnacipran treatment, or at the time drug
      treatment was stopped. The mean +/- SD decrease in VAS scores was 42.3 +/- 31.6
      (50.8 +/- 49.2%). One patient discontinued treatment after 4 weeks because of
      nausea, whereas others tolerated the agent well. These results suggest that the
      use of milnacipran in patients with a variety of chronic pain syndromes is
      beneficial. 

PMID- 24917236
TI  - Instruments to identify post-natal depression: Which methods have been the most
      extensively validated, in what setting and in which language?
AB  - Abstract Objectives. To investigate which methods to identify post-natal
      depression are the most extensively validated, in what setting and in what
      language. Methods. A systematic search of the literature was undertaken to
      retrieve English and non-English language articles available until February 2007.
      This included searching 16 electronic databases, forward citation searching,
      personal communication with authors and inspection of reference lists. Results. A
      total of 60 studies (published in 64 articles) met the inclusion criteria. Four
      PND specific measures and nine generic depression (and sometimes anxiety)
      measures were found to have been validated against a diagnostic reference
      standard in pregnant or post-natal populations. The Edinburgh Post-natal
      Depression Scale (EPDS) was the most frequently validated method to identify
      women with PND. The EPDS has been translated and validated in 20 different
      languages. The majority of studies were undertaken at ante-natal clinics (n=15),
      after the birth in post-natal wards (n=12) or during post-natal visits or follow
      up clinics (n=16). Conclusions. The EPDS is the most frequently researched method
      to identify PND and has been translated and validated in multiple different
      languages. 

PMID- 24917237
TI  - The involvement of the HLA-DQB1 alleles in the risk and the severity of Iranian
      coeliac disease patients.
AB  - Coeliac disease (CD) is a highly prevalent autoimmune disorder that is triggered
      by the ingestion of wheat gluten and related proteins in genetically susceptible
      individuals. The CD is associated with human leucocyte antigen (HLA) genes
      particularly with HLA-DQ alleles encoding HLA-DQ2 and DQ8 proteins. To define
      risk and severity alleles for CD, a total of 120 definite CD patients and 100
      healthy controls were genotyped for HLA-DQB1 gene. HLA-DQB1 genotyping was
      performed in all patients and controls using PCR-SSP technique, and to evaluate
      the clinical relevance of testing for HLA-DQB1 and determining absolute risk of
      disease, prevalence-corrected positive predictive value and prevalence-corrected
      negative predictive value (PcPPV and PcNPV) were calculated. Our results for a
      first time show that DQB1*02:00 and DQB1*03:02 alleles and DQB1*02:01/03:02
      genotype very significantly associated with increased risk of patients with CD,
      and DQB1*03:01,4 allele provides protection against CD in Iranian patients.
      Furthermore, the PcPPV for DQB*02:01 and 03:02 alleles in CD were 0.014 and
      0.012, respectively, and the highest absolute risk presented by DQB*0201/0302
      genotype (PcPPV = 0.079) and 98% of patients with CD carried DQB1*02:01/x or
      DQB1*03:02/x genotype. The results also clearly demonstrated that the DQB1*02:01
      allele significantly associated with severity of CD, while DQB1*03:02 allele
      associated with mild form of CD. These results suggest that clinically suspected
      individuals for CD and first-degree relatives of patients with CD to be screened
      for HLA-DQB*0201 and DQB*0302 alleles for possible early diagnosis and
      treatments.

PMID- 24917238
TI  - Participation and risk of high grade cytological lesions among immigrants and
      Italian-born women in an organized cervical cancer screening program in Central
      Italy.
AB  - Few studies analyzed the risk for high-grade squamous intraepithelial lesions or
      worse (HSIL+) among immigrants and natives attending organized cervical cancer
      (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+
      by country of birth with logistic models. Overall 540,779 invitation letters were
      delivered to target women of Florence SP in three screening rounds (years 2000
      2002, 2003-2005, 2006-2008). The probability of attending screening was lower for
      immigrants than natives, but the difference decreased from 35% (1st round) to 20%
      (2nd-3rd round) for women born in high migration pressure (HMP) countries. The
      risk of HSIL+ was double than natives for HMP-born women from countries with high
      prevalence of human papillomavirus, even adjusting for age and previous history
      of Pap test. This is an important public health problem due to an increasing
      proportion over time of immigrant women with a lower attendance and greater risk
      for CC.

PMID- 24917239
TI  - Prevalence of Blood Pressure, Blood Glucose and Serum Lipids Abnormalities Among
      Ethiopian Immigrants: A Community-Based Cross-Sectional Study.
AB  - The main objective of this study was to investigate the prevalence of
      hypertension, glucose and blood lipid abnormalities among a community of
      Ethiopian immigrants in Minnesota. This cross-sectional study used data from the
      parish nursing program 2007-2012. A total of 673 encounters were included in this
      study. Various dependent variables including systolic blood pressure (SBP),
      diastolic blood pressure (DBP), blood glucose (BG), and serum lipids were
      examined. High blood pressure was defined as a mean SBP equal to or higher than
      140 mm/Hg and/or DBP equal to or higher than 90 mmHg. Elevated fasting glucose
      defined as levels equal to or higher than 126 mg/dL. High level of total
      cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL)
      cholesterol, and low high-density lipoprotein (HDL) cholesterol were defined as
      >=240, >=200, >=160 and <=40 mg/dL, respectively. General linear regression
      models were used to investigate the relationship of participants' age and gender,
      to the continuously distributed response variables, which included systolic and
      DBP, BG, TC, TG, LDL cholesterol and HDL cholesterol. This is a nonrandom sample
      of adult Ethiopian church members who were invited to participate in a parish
      nurse cardiovascular disease (CVD) risk factor screening program. Participants in
      this sample were 43 % male and 57 % female. The overall prevalence of
      hypertension was 30.1 % with a cut off mark of 140/90 mm/Hg. The prevalence of
      hypertension was 33 and 24 % among men than among women, respectively (p < 0.01).
      Of all participants, 12 % had BG level of equal to or higher than 126 mg/dL. Low
      levels of HDL were reported in 30 % of the participants (<40 mg/dL). A higher
      prevalence of high LDL level (20 %) was observed among women compared to those
      found in men (16 %). High TC levels (>240 mg/dL) were observed in 15 % of the
      women and 10 % of the men (p = 0.2). Higher SBP and DBP were significantly higher
      in male participants than their female counterparts (p < 0.05) and in contrast,
      women showed a significantly higher TC (p < 0.01) and LDL (0.05) and HDL (p <
      0.001). Female participants also had higher BG than male participants but the
      difference was not statistically significant (p > 0.05). This opportunity sample
      suggests high prevalence of CVD risk factors in a community of Ethiopian-American
      adults, and a pressing need for more comprehensive and systematic assessment of
      chronic disease health needs in this growing community. 

PMID- 24917240
TI  - Exploring the Association of Homicides in Northern Mexico and Healthcare Access
      for US Residents.
AB  - Many legal residents in the United States (US)-Mexico border region cross from
      the US into Mexico for medical treatment and pharmaceuticals. We analyzed whether
      recent increases in homicides in Mexico are associated with reduced healthcare
      access for US border residents. We used data on healthcare access, legal entries
      to the US from Mexico, and Mexican homicide rates (2002-2010). Poisson regression
      models estimated associations between homicide rates and total legal US entries.
      Multivariate difference-in-difference linear probability models evaluated
      associations between Mexican homicide rates and self-reported measures of
      healthcare access for US residents. Increased homicide rates were associated with
      decreased legal entries to the US from Mexico. Contrary to expectations,
      homicides did not have significant associations with healthcare access measures
      for legal residents in US border counties. Despite a decrease in border
      crossings, increased violence in Mexico did not appear to negatively affect
      healthcare access for US border residents. 

PMID- 24917241
TI  - Persistent Desquamation of the Scalp as a Manifestation of Tinea Capitis in Sub
      Saharan Children.
AB  - Scalp hyperkeratosis of childhood is most often associated with atopic or
      seborrheic dermatitis. However, in black children can be associated with tinea
      capitis. We undertook a retrospective study in all Sub-Saharan children
      presenting with chronic scalp scaling between June 2010 and June 2013, to
      determine whether chronic desquamation of the scalp is a clinical manifestation
      of tinea capitis. The criterion used to diagnose tinea capitis was a positive
      mycolological culture. Of the 23 Sub-Saharan African children attended, 12
      (43.4%) presented with chronic scalp flaking. Mycological culture was performed
      in 9 of the 12 cases. The culture was positive in 6 out of 9, so 26% of the Sub
      Saharan African children attended were diagnosed with tinea capitis. In 52.1% of
      the cases with persistent scalp scaling the culture was positive. In conclusion,
      chronic scaling of the scalp may well be the sole form of presentation of tinea
      capitis in Sub-Saharan children.

PMID- 24917242
TI  - Cloning and characterization of feline islet glucokinase.
AB  - BACKGROUND: Glucokinase (GK) is a metabolic enzyme encoded by the GCK gene and
      expressed in glucose-sensitive tissues, principally pancreatic islets cell and
      hepatocytes. The GK protein acts in pancreatic islets as a "glucose sensor" that
      couples fluctuations in the blood glucose concentration to changes in cellular
      function and insulin secretion. GCK and GK have proposed importance in the
      development and progression of diabetes mellitus and are potential therapeutic
      targets for diabetes treatment. The study was undertaken to determine the
      nucleotide sequence of feline pancreatic GK cDNA, predict the amino acid sequence
      and structure of the feline GK protein, and perform comparative bioinformatic
      analysis of feline cDNA and protein. Routine PCR techniques were used with cDNA
      from feline pancreas. Clones were assembled to obtain the full length cDNA.
      Protein prediction and modeling were performed using bioinformatic tools.
      RESULTS: Full-length feline pancreatic GK cDNA contains a 1398 nucleotide coding
      sequence with high identity to other pancreatic GK cDNAs. The deduced 465 amino
      acid feline protein has 15 amino acid substitutions not found in other mammalian
      GK proteins but maintains high structural homology with human GK. Feline
      pancreatic GK is highly conserved at nucleotide and protein levels. Residues
      crucial for substrate binding and catalysis are completely conserved in the
      feline protein. CONCLUSION: Molecular analysis predicts that feline pancreatic GK
      functions similarly to other mammalian GK proteins.

PMID- 24917243
TI  - Identification of candidate long non-coding RNAs in response to myocardial
      infarction.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding
      RNAs. LncRNAs regulate gene expression, thus having the possibility to modulate
      disease progression. In this study, we investigated the changes of lncRNAs
      expression in the heart after myocardial infarction (MI). RESULTS: Adult male
      C57/BL6 mice were subjected to coronary ligation or sham operation. In a
      derivation group of 4 MI and 4 sham-operated mice sacrificed 24 hours after
      surgery, microarray analysis showed that MI was associated with up-regulation of
      20 lncRNAs and down-regulation of 10 lncRNAs (fold-change >2). Among these, 2
      lncRNAs, called myocardial infarction-associated transcript 1 (MIRT1) and 2
      (MIRT2), showed robust up-regulation in the MI group: 5-fold and 13-fold,
      respectively. Up-regulation of these 2 lncRNAs after MI was confirmed by
      quantitative PCR in an independent validation group of 8 MI and 8 sham-operated
      mice (9-fold and 16-fold for MIRT1 and MIRT2, P < 0.001). In a time-course
      analysis involving 21 additional MI mice, the expression of both lncRNAs peaked
      24 hours after MI and returned to baseline after 2 days. In situ hybridization
      revealed an up-regulation of MIRT1 expression in the left ventricle of MI mice.
      Expression of MIRT1 and MIRT2 correlated with the expression of multiple genes
      known to be involved in left ventricular remodeling. Mice with high level of
      expression of MIRT1 and MIRT2 had a preserved ejection fraction. CONCLUSION:
      Myocardial infarction induces important changes in the expression of lncRNAs in
      the heart. This study motivates further investigation of the role of lncRNAs in
      left ventricular remodeling.

PMID- 24917244
TI  - Transcriptional coexpression network reveals the involvement of varying stem cell
      features with different dysregulations in different gastric cancer subtypes.
AB  - Despite the advancements in the cancer therapeutics, gastric cancer ranks as the
      second most common cancers with high global mortality rate. Integrative
      functional genomic investigation is a powerful approach to understand the major
      dysregulations and to identify the potential targets toward the development of
      targeted therapeutics for various cancers. Intestinal and diffuse type gastric
      tumors remain the major subtypes and the molecular determinants and drivers of
      these distinct subtypes remain unidentified. In this investigation, by exploring
      the network of gene coexpression association in gastric tumors, mRNA expressions
      of 20,318 genes across 200 gastric tumors were categorized into 21 modules. The
      genes and the hub genes of the modules show gastric cancer subtype specific
      expression. The expression patterns of the modules were correlated with
      intestinal and diffuse subtypes as well as with the differentiation status of
      gastric tumors. Among these, G1 module has been identified as a major driving
      force of diffuse type gastric tumors with the features of (i) enriched
      mesenchymal, mesenchymal stem cell like, and mesenchymal derived multiple
      lineages, (ii) elevated OCT1 mediated transcription, (iii) involvement of Notch
      activation, and (iv) reduced polycomb mediated epigenetic repression. G13 module
      has been identified as key factor in intestinal type gastric tumors and found to
      have the characteristic features of (i) involvement of embryonic stem cell like
      properties, (ii) Wnt, MYC and E2F mediated transcription programs, and (iii)
      involvement of polycomb mediated repression. Thus the differential transcription
      programs, differential epigenetic regulation and varying stem cell features
      involved in two major subtypes of gastric cancer were delineated by exploring the
      gene coexpression network. The identified subtype specific dysregulations could
      be optimally employed in developing subtype specific therapeutic targeting
      strategies for gastric cancer.

PMID- 24917245
TI  - Temporal trends in population-based death rates associated with chronic liver
      disease and liver cancer in the United States over the last 30 years.
AB  - BACKGROUND: The health and economic burden from liver disease in the United
      States is substantial and rising. The objective of this study was to characterize
      temporal trends in mortality from chronic liver disease and liver cancer and the
      incidence of associated risk factors using population-based data over the past 30
      years. METHODS: Population-based mortality data were obtained from the National
      Vital Statistics System, and population estimates were derived from the national
      census for US adults (aged >45 years). Crude death rates (CDRs), age-adjusted
      death rates (ADRs), and average annual percentage change (AAPC) statistics were
      calculated. RESULTS: In total, 690,414 deaths (1.1%) were attributable to chronic
      liver disease, whereas 331,393 deaths (0.5%) were attributable to liver cancer
      between 1981 and 2010. The incidence of liver cancer was estimated at 7.1 cases
      per 100,000 population. Mortality rates from chronic liver disease and liver
      cancer increased substantially over the past 3 decades, with ADRs of 23.7 and
      16.6 per 100,000 population in 2010, respectively. The AAPC from 2006 to 2010
      demonstrated an increased ADR for chronic liver disease (AAPC, 1.5%; 95%
      confidence interval, 0.3%-2.8%) and liver cancer (AAPC, 2.6%; 95% confidence
      interval, 2.4%-2.7%). CONCLUSIONS: A comprehensive approach that involves primary
      and secondary prevention, increased access to treatment, and more funding for
      liver-related research is needed to address the high death rates associated with
      chronic liver disease and liver cancer in the United States.

PMID- 24917246
TI  - Targeting the TGF-beta receptor with kinase inhibitors for scleroderma therapy.
AB  - Scleroderma (systemic sclerosis) is a connective tissue disease that affects
      various organ systems; the treatment of scleroderma is still difficult and
      remains a challenge to the clinician. Recently, kinase inhibitors have shown
      great potential against fibrotic diseases and, specifically, the transforming
      growth factor-beta receptor (TGF-betaR) was found as a new and promising target
      for scleroderma therapy. In the current study, we propose that the large pool of
      existing kinase inhibitors could be exploited for inhibiting the TGF-betaR to
      suppress scleroderma. In this respect, we developed a modeling protocol to
      systematically profile the inhibitory activities of 169 commercially available
      kinase inhibitors against the TGF-betaR, from which five promising candidates
      were selected and tested using a standard kinase assay protocol. Consequently,
      two molecular entities, namely the PKB inhibitor MK-2206 and the mTOR C1/C2
      inhibitor AZD8055, showed high potency when bound to the TGF-betaR, with IC50
      values of 97 and 86 nM, respectively, which are close to those of the recently
      developed TGF-betaR selective inhibitors SB525334 and LY2157299 (IC50 = 14.3 and
      56 nM, respectively). We also performed atomistic molecular dynamics simulations
      and post-molecular mechanics/Poisson-Boltzmann surface area analyses to dissect
      the structural basis and energetic properties of intermolecular interactions
      between the TGF-betaR kinase domain and these potent compounds, highlighting
      intensive nonbonded networks across the tightly packed interface of non-cognate
      TGF-betaR-inhibitor complexes.

PMID- 24917247
TI  - Measurement of habitual physical activity and sedentary behaviour of youth with
      cerebral palsy: work in progress.

PMID- 24917248
TI  - Lithium cycling in a self-assembled copper chloride-polyether hybrid electrode.
AB  - Atomic-scale integration of polyether molecules and copper(II) chloride layers in
      a two-dimensional perovskite affords, to the best of our knowledge, the first
      example of extended Li(+) cycling in a metal chloride electrode. The hybrid can
      cycle over 200 times as a cathode in a lithium battery with an open-circuit
      voltage of 3.2 V. In contrast, CuCl2 alone or the precursors to the hybrid cannot
      be cycled in a lithium battery, demonstrating the importance of the layered,
      organic-inorganic architecture. This work shows that appropriate organic groups
      can enable Li(+) cycling in inexpensive, nontoxic, metal halide electrodes, which
      is promising for large-scale applications. 

PMID- 24917249
TI  - Is evolutionary biology becoming too politically correct? A reflection on the
      scala naturae, phylogenetically basal clades, anatomically plesiomorphic taxa,
      and 'lower' animals.
AB  - The notion of scala naturae dates back to thinkers such as Aristotle, who placed
      plants below animals and ranked the latter along a graded scale of complexity
      from 'lower' to 'higher' animals, such as humans. In the last decades,
      evolutionary biologists have tended to move from one extreme (i.e. the idea of
      scala naturae or the existence of a general evolutionary trend in complexity from
      'lower' to "higher" taxa, with Homo sapiens as the end stage) to the other,
      opposite, extreme (i.e. to avoid using terms such as 'phylogenetically basal' and
      'anatomically plesiomorphic' taxa, which are seen as the undesired vestige of old
      teleological theories). The latter view tries to avoid any possible connotations
      with the original anthropocentric idea of a scala naturae crowned by man and, in
      that sense, it can be regarded as a more politically correct view. In the past
      years and months there has been renewed interest in these topics, which have been
      discussed in various papers and monographs that tend to subscribe, in general, to
      the points defended in the more politically correct view. Importantly, most
      evolutionary and phylogenetic studies of tetrapods and other vertebrates, and
      therefore most discussions on the scala naturae and related issues have been
      based on hard tissue and, more recently, on molecular data. Here we provide the
      first discussion of these topics based on a comparative myological study of all
      the major vertebrate clades and of myological cladistic and Bayesian phylogenetic
      analyses of bony fish and tetrapods, including Primates. We specifically (i)
      contradict the notions of a scala naturae or evolutionary progressive trends
      leading to more complexity in 'higher' animals and culminating in Homo sapiens,
      and (ii) stress that the refutation of these old notions does not necessarily
      mean that one should not keep using the terms 'phylogenetically basal' and
      particularly 'anatomically plesiomorphic' to refer to groups such as the urodeles
      within the Tetrapoda, or the strepsirrhines and lemurs within the Primates, for
      instance. This review will contribute to improving our understanding of these
      broad evolutionary issues and of the evolution of the vertebrate Bauplans, and
      hopefully will stimulate future phylogenetic, evolutionary and developmental
      studies of these clades. 

PMID- 24917250
TI  - Spatial and temporal patterns of larval dispersal in a coral-reef fish
      metapopulation: evidence of variable reproductive success.
AB  - Many marine organisms can be transported hundreds of kilometres during their
      pelagic larval stage, yet little is known about spatial and temporal patterns of
      larval dispersal. Although traditional population-genetic tools can be applied to
      infer movement of larvae on an evolutionary timescale, large effective population
      sizes and high rates of gene flow present serious challenges to documenting
      dispersal patterns over shorter, ecologically relevant, timescales. Here, we
      address these challenges by combining direct parentage analysis and indirect
      genetic analyses over a 4-year period to document spatial and temporal patterns
      of larval dispersal in a common coral-reef fish: the bicolour damselfish
      (Stegastes partitus). At four island locations surrounding Exuma Sound, Bahamas,
      including a long-established marine reserve, we collected 3278 individuals and
      genotyped them at 10 microsatellite loci. Using Bayesian parentage analysis, we
      identified eight parent-offspring pairs, thereby directly documenting dispersal
      distances ranging from 0 km (i.e., self-recruitment) to 129 km (i.e., larval
      connectivity). Despite documenting substantial dispersal and gene flow between
      islands, we observed more self-recruitment events than expected if the larvae
      were drawn from a common, well-mixed pool (i.e., a completely open population).
      Additionally, we detected both spatial and temporal variation in signatures of
      sweepstakes and Wahlund effects. The high variance in reproductive success (i.e.,
      'sweepstakes') we observed may be influenced by seasonal mesoscale gyres present
      in the Exuma Sound, which play a prominent role in shaping local oceanographic
      patterns. This study documents the complex nature of larval dispersal in a coral
      reef fish, and highlights the importance of sampling multiple cohorts and
      coupling both direct and indirect genetic methods in order disentangle patterns
      of dispersal, gene flow and variable reproductive success. 

PMID- 24917251
TI  - Successful treatment of intractable complex regional pain syndrome type I of the
      knee with dorsal root ganglion stimulation: a case report.
AB  - OBJECTIVES: To report on the efficacy of dorsal root ganglion stimulation in a
      patient with complex regional pain syndrome (CRPS) type I of the knee. MATERIALS
      AND METHODS: A 48-year-old woman with CRPS type I of the right knee, diagnosed
      according to the Budapest criteria set, received DRG stimulation for intractable
      CRPS type I of the knee. RESULTS: After a successful trial period with three DRG
      stimulation leads on spinal levels L2, L3, and L4 (covering 90% of the painful
      area of her knee), a definitive pulse generator was implanted. Three months after
      implantation, the entire painful area was covered, and the patient reported a
      numeric rating scale score of 1-2. CONCLUSION: Placement of three DRG stimulation
      leads at levels L2, L3, and L4 in a patient with intractable CRPS type I of the
      knee resulted in major pain relief. We recommend further investigation of the
      effect of DRG stimulation on pain due to CRPS of the knee.

PMID- 24917252
TI  - Notes from the guest editor.
AB  - In 2009, four institutes of the Canadian Institutes of Health Research (Gender
      and Health; Health Services and Policy Research; Neurosciences, Mental Health and
      Addiction; and Population and Public Health) sponsored the Fourth Annual Canadian
      Research Congress on Mental Health and Addictions in the Workplace, in Toronto,
      Ontario. Hosted by the Work and Well-Being Research and Evaluation Program at the
      Centre for Addiction and Mental Health, the theme of the congress was We Can Do
      It! Evidence and Interventions for Transforming Mental Health in the Workplace
      (see http://www.kewa.camh.net/researchers/areas/work_wellbeing/Pages/default.aspx
      for more details). Coincidentally, in the same year, an idealistic presidential
      hopeful named Barack Obama adopted a similar slogan for his White House run.
      Obama recognized that change that challenges established barriers can only come
      about through co-operation and a collective investment. 

PMID- 24917253
TI  - Psychosocial and biological indicators in the evaluation of and intervention in
      mental health problems at work.
AB  - This article discusses how biological and psychosocial perspectives might
      integrate into a unified framework - the bio-psychosocial model - that can be
      used to explain how mental health problems at work are generated and that can be
      subsequently employed in workplace intervention. It concludes with a brief review
      of the advantages and ethical pitfalls that arise with this approach. 

PMID- 24917254
TI  - Law, public policy and mental health in the workplace.
AB  - The first part of this article describes regulatory interventions, drawn from
      different Canadian jurisdictions, designed to reduce worker exposure to
      psychosocial hazards, including occupational violence, and to protect workers'
      mental health. It also addresses legislative provisions providing workers'
      compensation for mental health problems and regulatory provisions supporting the
      return to work of those who have been absent from work because of work-related
      mental health problems. The second part of the article, relying on illustrations
      from case law in which workers' compensation claims for mental health problems
      have been accepted, examines ways in which law and policy can actually contribute
      directly or indirectly to behaviours that may lead to increasing illness and
      disability associated with mental health problems. 

PMID- 24917255
TI  - Workplace design contributions to mental health and well-being.
AB  - People spend much of their waking time in their workplaces (approximately 33% on
      a weekly basis), which raises the possibility that the conditions they experience
      at work influence their health and well-being. The workplace design literature
      has given scant attention to mental health outcomes, instead focusing on healthy
      populations. Conversely, the mental health literature gives scant attention to
      the potential contribution of workplace design in preventing mental health
      problems; nor does it provide much insight into facilitating return to work.
      Taken together, however, the literature does suggest both lines of research and
      possible interventions. Existing knowledge proposes that workplace design can
      influence mental health via the effects of light exposure on circadian
      regulation, social behaviour and affect; the effects of aesthetic judgement on at
      work mood and physical well-being and at-home sleep quality; access to nature and
      recovery from stressful experiences; and privacy regulation and stimulus control.
      This paper includes a short review of the literature in this area, proposals for
      new research directions and consideration of the implications of this information
      on the design choices made by business owners, designers and facility managers.
      Providing suitable working conditions for all employees avoids stigmatizing
      employees who have mental health problems, while facilitating prevention and
      return to work among those who do. 

PMID- 24917256
TI  - Intervention study on psychosocial work factors and mental health and
      musculoskeletal outcomes.
AB  - Organizations are facing ever-stiffer competition in the current globalized
      economy, and employees are consequently being exposed to increasingly adverse
      psychosocial work factors. Psychosocial work factors, also called psychosocial
      stressors, refer to all organizational factors and interpersonal relationships in
      the workplace that may affect workers' health. Two well-defined and
      internationally recognized theoretical models are used to assess these factors:
      the Karasek demand-latitude-support model and the Siegrist effort-reward
      imbalance model. The Karasek and Siegrist models reflect specific components of
      the work environment for which there is empirical evidence of a deleterious
      effect on health. Preventive interventions targeting these factors are conducted
      in workplaces. However, few studies have rigorously documented these
      interventions and their effectiveness in reducing adverse work factors and
      improving health outcomes. Most previous intervention studies were limited by (1)
      a short follow-up that may not have provided sufficient time for effects to
      appear, (2) small sample sizes (N <= 100) that limited the statistical power and
      the possibility of detecting results and (3) rare assessment of the Siegrist
      model. The current paper presents the overall design and the main results of an
      intervention study on psychosocial work factors and related mental health and
      musculoskeletal outcomes. The study integrated (1) a development phase that aimed
      at identifying the changes needed to reduce psychosocial factors in the target
      population and the best ways to bring about these changes, (2) an implementation
      phase that systematically documented how the intervention was carried out and (3)
      an effectiveness phase that evaluated whether the intervention was successful in
      reducing adverse psychosocial work factors and health problems. In addition, the
      study used repeated measurements of psychosocial work factors and health
      indicators at baseline and six and 30 months post-intervention to assess short-
      and medium-term effects of the intervention.

PMID- 24917257
TI  - Intervention research on working conditions and mental health: persistent
      challenges, new directions and opportunities to integrate research agendas.
AB  - This commentary provides a summary of the four preceding research papers. Three
      of the four papers, those by Gilbert-Ouimet et al., Marchand and Durand, and
      Veitch, provide direction for future workplace psychosocial intervention studies,
      while the remaining paper, by Lippel, offers insight into how existing
      occupational health and safety and workers' compensation legislation offers few
      motivations for employers to promote and protect the mental health of their
      employees. In addition to fleshing out the directions and insight offered by
      these papers, this commentary flags the challenges that persist in this area of
      intervention research. To conclude, the authors offer a summary of directions for
      future research, including opportunities to integrate research agendas. 

PMID- 24917258
TI  - Advancing research on mental health in the workplace.
AB  - A complex topic like workplace mental health requires multidisciplinary, multi
      sectoral, mixed methods research and effective knowledge translation of research
      findings. In this commentary, two of the 13 institutes that comprise the Canadian
      Institutes of Health Research - the institute of Gender and Health and the
      Institute of Population and Public Health - discuss strategies for advancing
      research on mental health and the workplace. With a focus on each Institute's
      mandate, the commentary argues that there is a need to advance our understanding
      of how biological, social, cultural and environmental determinants of workplace
      mental health are influenced by sex and gender, and of how population health
      intervention research can generate evidence that will strengthen the impact of
      workplace interventions to reduce mental illness. 

PMID- 24917259
TI  - The business case: collaborating to help employees maintain their mental well
      being.
AB  - There has been a change in the mindset of businesses in recent years. Companies
      are starting to realize that proactively helping their employees to maintain
      mental health is beneficial, both for their workers and their business. In this
      article, we present three different but complementary views - those of an
      advocate, an employer and a provider - on helping employees maintain mental, and
      physical, health. In the first section, Sari Sairanen outlines programs and
      services to manage stress and maintain mental health that have been developed by
      the Canadian Auto Workers' union and implemented in partnership with employers,
      wellness providers, service agencies and other community partners. The union
      focuses on raising awareness and providing education, as well as removing the
      stigma associated with mental illness. Deanna Matzanke, in her section, discusses
      the commitment of a company, Scotiabank, to create and maintain an inclusive and
      accessible workplace for all its employees. It has recently worked with providers
      to develop and implement integrated services dealing specifically with mental
      health illness and addiction, which aid not only its current employees but also
      possible future employees. Finally, Doug Smeall shares his observations as an
      insurer at Sun Life Financial, who has seen the rates of both short-term and long
      term disabilities increase. He elaborates on the collaborative work between
      insurers and employers to help employees maintain their mental health, and to
      return to work sooner when issues do occur. Ultimately, this article argues that
      unions, employers and insurers can work together with partners and employees to
      promote and maintain employee health because, as Sairanen asserts, "preventing a
      problem in the first place is the best strategy." 

PMID- 24917260
TI  - Opportunities abound to improve mental health and psychological safety in the
      workplace.
AB  - This commentary provides a brief synopsis of the views expressed by the authors
      of the invited essay "The Business Case," Sari Sairanen, Deanna Matzanke and Doug
      Smeall. It then discusses the authors' views in light of the Mental Health
      Commission's framework for a Mental Health Strategy for Canada, titled Toward
      Recovery and Well-Being, and Dr. Martin Shain's two reports to the Mental Health
      Commission of Canada - Stress at Work, Mental Injury and the Law in Canada and
      Tracking the Perfect Legal Storm. The initiatives discussed in the lead paper are
      then compared with a 2009 consensus statement generated at a forum co-hosted by
      the Mental Health Commission and the Great-West Life Centre for Mental Health in
      the Workplace. The consensus statement reflects the recommendation of the forum's
      40 participants that a Canadian national standard for psychological health and
      safety in the workplace should be developed. 

PMID- 24917261
TI  - Welcome to our world.
AB  - Richard Branson, David Neeleman and Paul Orfalea - what do these entrepreneurs
      have in common, other than wealth? They have a disorder that affects about one in
      25 adults in North America - Attention Deficit/Hyperactivity Disorder. In this
      article, comedian and TV producer Rick Green outlines some of the history and
      costs of the disorder, and shares with us first-hand insight into the struggles -
      and rewards - this disorder can present. 

PMID- 24917262
TI  - Effects of transient blur and VDT screen luminance changes on eyeblink rate.
AB  - PURPOSE: A study was designed to evaluate the efficacy of three different
      strategies aiming at increasing spontaneous eyeblink rate (SEBR) during computer
      use. METHODS: A total of 12 subjects (5 female) with a mean age of 28.7 years
      were instructed to read a text presented on a computer display terminal during
      15min. Four reading sessions (reference and three "blinking events" [BE]) were
      programmed in which SEBR was digitally recorded. "Blinking events" were based on
      either a slight distortion of the text characters or on the presentation of a
      white screen instead of the text, with or without accompanying blinking
      instructions. All BE had a duration of 20ms and occurred every 15s. Participants
      graded the intrusiveness of each BE configuration, and the number of lines
      participants read in each session was recorded. RESULTS: Data from 11 subjects
      was analysed. A statistically significant difference in SEBR was encountered
      between the experimental configuration consisting on a white screen plus blinking
      instructions (7.8 blinks/min) and both reference (5.2 blinks/min; p=0.049) and
      white screen without blinking instructions (4.8 blinks/min; p=0.038). All three
      BE had superior levels of intrusiveness than reference conditions, although the
      performance of participants (line count) was not compromised. CONCLUSIONS: The
      joint contribution of white screen and blinking instructions has been shown to
      result in a short term improvement in blinking rate in the present sample of non
      dry eye computer users. Further work is necessary to improve the acceptance of
      any BE aiming at influencing SEBR.

PMID- 24917263
TI  - The language of feelings: A reading and storytelling group in an adolescent unit.
AB  - This article describes a "Reading and Storytelling Group" that ran at an
      adolescent inpatient unit and outlines how fictional stories, both read and told,
      can develop psychological insights such as mentalization and emotional literacy.
      The structure of the group is described, and some of the activities and responses
      of the young people are illustrated. How activities such as this can have
      therapeutic benefits without being ostensibly "therapy" are discussed. 

PMID- 24917264
TI  - Quality measures for palliative care in patients with cancer: a systematic
      review.
AB  - PURPOSE: Quality assessment is a critical component of determining the value of
      medical services, including palliative care. Characterization of the current
      portfolio of measures that assess the quality of palliative care delivered in
      oncology is necessary to identify gaps and inform future measure development.
      METHODS: We performed a systematic review of MEDLINE/PubMed and the gray
      literature for quality measures relevant to palliative care. Measures were
      categorized into National Quality Forum domains and reviewed for methodology of
      development and content. Measures were additionally analyzed to draw summative
      conclusions on scope and span. RESULTS: Two hundred eighty-four quality measures
      within 13 measure sets were identified. The most common domains for measure
      content were Physical Aspects of Care (35%) and Structure and Processes of Care
      (22%). Of symptom-related measures, pain (36%) and dyspnea (26%) were the most
      commonly addressed. Spiritual (4%) and Cultural (1%) Aspects of Care were least
      represented domains. Generally, measures addressed processes of care, did not
      delineate benchmarks for success, and often did not specify intended
      interventions to address unmet needs. This was most evident regarding issues of
      psychosocial and spiritual assessment and management. CONCLUSION: Within a large
      cohort of quality measures for palliative, care is often a focus on physical
      manifestations of disease and adverse effects of therapy; relatively little
      attention is given to the other aspects of suffering commonly observed among
      patients with advanced cancer, including psychological, social, and spiritual
      distress.

PMID- 24917265
TI  - Claiming an Ethic of Care for midwifery.
AB  - BACKGROUND: The public domain of midwifery practice, represented by the
      educational and hospital institutions could be blamed for a subconscious ethical
      dilemma for midwifery practitioners. The result of such tension can be seen in
      complaints from maternity service users of dehumanised care. When expectations
      are not met, women report dehumanising experiences that carry long term
      consequences to both them and their child. OBJECTIVES: To revisit the ethical
      foundation of midwifery practice to reflect the feminist Ethic of Care and
      reframe what is valuable to women and midwives during the childbirth experience.
      RESEARCH DESIGN: A comprehensive literature review is presented from the
      midwifery and feminist ethics discourse. ETHICAL CONSIDERATIONS: Nil to report.
      FINDINGS: Women are vulnerable during childbirth as they need care, yet they
      prioritise elements of relationship in their experience. The Ethic of Care
      approach equalises the relationship between the midwife and the woman, providing
      the space for relationship building and allowing midwives to meet the
      expectations of their accepted responsibility. DISCUSSION: Some midwives manage
      to balance the demands of the institution with the needs of the woman. This is
      described as both an emotional and professionally challenging balancing act.
      CONCLUSION: Until there is a formal acknowledgement of the different ethical
      approach to midwifery practice from within the profession and the Institution,
      midwifery identity and practice will continue to be compromised.

PMID- 24917266
TI  - Moral distress in nurses at an acute care hospital in Switzerland: results of a
      pilot study.
AB  - BACKGROUND: In the context of new reimbursement systems like diagnosis-related
      groups, moral distress is becoming a growing problem for healthcare providers.
      Moral distress can trigger emotional and physical reactions in nurses and can
      cause them to withdraw emotionally from patients or can cause them to change
      their work place. OBJECTIVE: The aim of this pilot study was to develop an
      instrument to measure moral distress among acute care nurses in the German
      speaking context, to test its applicability, and to obtain initial indications of
      the instrument's validity. METHOD: The study was designed in 2011 as a cross
      sectional pilot survey. Conducted on eight units of one university hospital in
      German-speaking Switzerland, 294 registered nurses were asked to fill out a web
      based questionnaire on moral distress. ETHICAL CONSIDERATIONS: The study proposal
      was approved by the cantonal ethics committee. All participating nurses provided
      informed consent and were assured of data confidentiality. RESULTS: The survey
      had a response rate of 55%. The results show the prevalence of statements on the
      questionnaire indicating situations with the potential to trigger moral distress.
      The entire range of answers was used in the responses. Most participants found
      the questionnaire comprehensible, while some criticized the phraseology of
      certain statements. Many more found the registration process prior to online
      access to be too time consuming. Nurses confirmed that the results reflect their
      subjective assessment of their situation and their experience of moral distress.
      CONCLUSION: The newly developed moral distress questionnaire appears to produce
      face validity and is sufficiently applicable for use in our study. The results
      indicate that moral distress appears to be a relevant phenomenon also in Swiss
      hospitals and that nurses were experiencing it prior to the introduction of Swiss
      diagnosis-related groups.

PMID- 24917267
TI  - Ethical considerations on the value of patient knowledge in long-term care: a
      qualitative study of patients suffering from Korsakoff 's syndrome.
AB  - AIM: This study explores experiences of patients suffering from Korsakoff's
      syndrome. It contributes to improved reflection on the value of patient
      knowledge. BACKGROUND: An ethics of care perspective states the importance of
      moving to patients in their vulnerable state of being, and to figure out
      patients' individual needs necessary to provide good care. The information given
      by patients suffering from Korsakoff's syndrome might be mistaken, invented and
      even not true. The value of these patients' experiences and knowledge had not
      been researched to date. METHOD: Data from six in-depth interviews were analysed
      concurrently through the constant comparative method. ETHICAL CONSIDERATIONS: The
      principles of voluntariness, confidentiality and anonymity were respected during
      the research process. FINDINGS: Four important themes within patients' knowledge
      emerged: health condition, involuntary admission into the nursing home, the daily
      routine and interpretation of the caring abilities of healthcare professionals.
      The findings show that our respondents were able to provide a window into their
      inner perspective. CONCLUSION: This study deepens our understanding of the value
      of patient knowledge in situations where patients see the world in a different
      manner as do healthcare professionals. The conversations revealed personal
      subjective knowledge which our respondents create and live by. Healthcare
      professionals are encouraged to discover and affirm the understandings of these
      patients, and not be prepossessed due to the diagnosis or general nursing home
      rules. Understanding patients' unique knowledge through appreciation of the
      complexity and richness of different views on the situation can assist to give a
      more humane response to individual needs and pain. Health staff in healthcare
      institutions are encouraged to evaluate the - unintended - effect of rigidly
      applied nursing home rules, and the government is challenged to rethink its
      policy about care, and provide more resources permitting relational care that
      nurtures the dignity of patients suffering from Korsakoff's syndrome.

PMID- 24917268
TI  - Toward interventions to address moral distress: navigating structure and agency.
AB  - BACKGROUND: The concept of moral distress has been the subject of nursing
      research for the past 30 years. Recently, there has been a call to move from
      developing an understanding of the concept to developing interventions to help
      ameliorate the experience. At the same time, the use of the term moral distress
      has been critiqued for a lack of clarity about the concepts that underpin the
      experience. DISCUSSION: Some researchers suggest that a closer examination of how
      socio-political structures influence healthcare delivery will move moral distress
      from being seen as located in the individual to an experience that is also
      located in broader healthcare structures. Informed by new thinking in relational
      ethics, we draw on research findings from neuroscience and attachment literature
      to examine the reciprocal relationship between structures and agents and frame
      the experience of moral distress. CONCLUSION: We posit moral distress as a form
      of relational trauma and subsequently point to the need to better understand how
      nurses as moral agents are influenced by-and influence-the complex socio
      political structures they inhabit. In so doing, we identify this reciprocity as a
      framework for interventions.

PMID- 24917269
TI  - Developing nursing ethical competences online versus in the traditional
      classroom.
AB  - BACKGROUND: The development of society and science, especially medical science,
      gives rise to new moral and ethical challenges in healthcare. RESEARCH
      QUESTION/OBJECTIVES/HYPOTHESIS: In order to respond to the contemporary
      challenges that require autonomous decision-making in different work contexts, a
      pedagogical experiment was conducted to identify the readiness and responsiveness
      of current organisation of nursing higher education in Slovenia. It compared the
      successfulness of active learning methods online (experimental group) and in the
      traditional classroom (control group) and their impact on the ethical competences
      of nursing students. The hypothesis set in the experiment, hypothesis 1 (the
      experimental group will be successful and will have good achievements in
      comprehension and application of ethical principles) was confirmed based on pre
      tests and post-tests. The hypothesis tested by the questionnaire, hypothesis 2
      (according to the students, the active learning methods online in the
      experimental group have a positive impact on the development of ethical
      competences) was confirmed. RESEARCH DESIGN: The pedagogical experiment was
      supported by a multiple-case study that enabled the in-depth analysis of the
      students' attitudes towards the active learning methods in both settings.
      PARTICIPANTS AND RESEARCH CONTEXT: The study included Slovenian first-year
      nursing students (N = 211) of all the enrolled students (N = 225) at the
      University of Ljubljana and University of Primorska in the academic year
      2010/2011. ETHICAL CONSIDERATIONS: Before the study ethical permission was
      obtained from the managements of both participating faculties. The students were
      given all the necessary information of the experiment before the tutorials.
      FINDINGS: No significant difference was found between the two learning settings
      and both had a positive impact upon learning. The results of the content analysis
      show that the students' active engagement with the active learning methods in the
      group enables the development of ethical competences and the related
      communicative competences, interpersonal skills, collaboration and critical
      thinking. DISCUSSION: Active learning methods in the settings compared, online
      and the traditional classroom, enabled the development of a higher level of
      knowledge defined by the ability of critical thinking and reflective response,
      the core of ethical competences. Students develop ethical competence through
      active engagement in a group work, role play and discussion, and there is no
      difference between online or traditional learning settings. CONCLUSION: In the
      healthcare, it is crucial for providers to be capable of making autonomous
      decisions and managing various communication situations and contexts in which the
      moral attitudes and ethical sensibility are essential.

PMID- 24917270
TI  - Ethical challenges when caring for dying children.
AB  - BACKGROUND: Caring for dying children presents special challenges, according to
      the children themselves, their relatives and healthcare professionals. OBJECTIVE:
      The aim of this study was to describe caring as represented in healthcare
      workers' experiences of caring for dying children. METHOD: A phenomenological
      approach was chosen, in-depth interviews were carried out and data were analysed
      in four steps focusing on (a) open reading, (b) meaning units, (c) constituents
      and (d) essence. ETHICAL CONSIDERATIONS: Four nurses in a general acute
      paediatric care setting in Sweden participated after providing written informed
      consent. Voluntary participation and confidentiality were ensured, and the study
      was ethically approved. FINDINGS: The essence of caring for dying children was
      likened to a musically attuned composition, comprising five constituents:
      presence, self-knowledge, injustice in dying, own suffering and in need of
      others. Presence was found to be a prerequisite for caring when a child is dying.
      Self-knowledge and support from others can be of help when struggling with
      emotional pain and injustice. DISCUSSION: Caring for dying children has been
      found to be a delicate task for healthcare workers all over the world, and the
      ethical dimension is emphasized in international research. In this study,
      emotional pain and suffering accompanied caring, but an atmosphere in which it is
      possible to give and get support from colleagues and to have time to grieve and
      time to focus on the patient's needs may ease the burden, as can having time to
      process thoughts about life and death, and a possibility to grow in self
      knowledge. CONCLUSION: Caring in ethically demanding situations may be
      facilitated through presence, atmosphere, self-knowledge and time. The challenge
      does not demand highly technological solutions; these assets are readily
      available, no matter where on earth. However, there is a need to further
      investigate these prerequisites for caring, particularly when a child is dying.

PMID- 24917271
TI  - Neonatal influenza infection causes pathological changes in the mouse brain.
AB  - Influenza A virus infections have been proposed to be associated with a broad
      spectrum of central nervous system complications that range from acute
      encephalitis/encephalopathy to neuropsychiatric disorders in humans. In order to
      study early influenza virus exposure in the brain, we created an influenza
      infection model in neonatal mice to investigate infection route and resulting
      pathological changes in the brain. Real-time polymerase chain reaction and
      immunohistochemical analyses showed that influenza virus infection induced by an
      intraperitoneal injection was first detected as early as 1 day post infection
      (dpi), and the peak infection was observed at 5 dpi. The viral antigen was
      detected in a wide range of brain regions, including: the cerebral cortex,
      hippocampus, cerebellum, and brainstem. Apoptotic cell death and gliosis were
      detected in the areas of viral infection. Significant increases in
      proinflammatory cytokine expression were also observed at 5 dpi. Viral RNAs were
      detected in the cerebrospinal fluid of infected adult mice as early as 1 dpi. In
      addition, many infected cells were observed near the ventricles, indicating that
      the virus may enter the brain parenchyma through the ventricles. These results
      demonstrate that influenza virus may effectively infect broad regions of the
      brain through the hematogenous route, potentially through the cerebrospinal fluid
      along the ventricles, and subsequently induce neuropathological changes in the
      neonatal mouse brain.

PMID- 24917272
TI  - Increased health care utilization by survivors of childhood lymphoblastic
      leukemia is confined to those treated with cranial or total body irradiation: a
      case cohort study.
AB  - BACKGROUND: Previous studies have indicated that survivors of childhood acute
      lymphoblastic leukemia (ALL) have an increased morbidity measured in terms of
      health care utilization. However, earlier studies have several potentially
      important limitations. To overcome some of these, we investigated hospital
      contact rates, and predictors thereof, among 5-year survivors of ALL in a
      population-based setting, and compared them to a control cohort regarding outcome
      measures from a comprehensive nation-wide health register. METHODS: All
      individuals diagnosed with ALL before the age of 18 in Southern Sweden during
      1970-1999 and alive January 2007 (n=213; male=107) were identified through the
      Swedish Cancer Register. Each subject was matched to fifty controls, identified
      in the Swedish Population Register. All study subjects were linked to the
      National Hospital Register and detailed information was obtained on all hospital
      contacts (hospital admissions and outpatients visits) starting five years after
      cancer diagnosis, and the corresponding date for the controls, until 2009.
      RESULTS: The median follow-up among the 5-year survivors of ALL was 16 years
      (range 5-33), accruing a total of 3,527 person-years. Of the 213 5-year
      survivors, 105 (49.3%) had at least one hospital contact compared to 3,634
      (34.1%) of the controls (p<0.001). Survivors had more hospital contacts (3 [1-6]
      vs. 2 [1-4] contacts, p<0.001) and more total days in hospital (6 [2-18] vs. 3 [1
      7] days, p<0.001) than the controls during the study period. Logistic regression
      analysis showed that survivors treated with cranial irradiation and/or total body
      irradiation (45% and 7%, respectively) had an increased risk of at least one
      hospital contact (OR 2.3, 95%CI; 1.5-3.6 and OR 11.0, 95%CI; 3.2-50.7,
      respectively), while there was no significant difference between the non
      irradiated survivors and controls. CONCLUSIONS: We show that irradiated survivors
      of childhood ALL have an increased morbidity measured in terms of hospital
      contacts, in comparison to non-irradiated survivors and controls, while non
      irradiated survivors have not. These findings are encouraging regarding the
      future morbidity of children currently treated for ALL, as radiotherapy is
      necessary only for a minority of these.

PMID- 24917274
TI  - Effect of the Nicotinic alpha4beta2-receptor Partial Agonist Varenicline on Non
      invasive Brain Stimulation-Induced Neuroplasticity in the Human Motor Cortex.
AB  - Nicotine alters cognitive functions in animals and humans most likely by
      modification of brain plasticity. In the human brain, it alters plasticity
      induced by transcranial direct current stimulation (tDCS) and paired associative
      stimulation (PAS), probably by interference with calcium-dependent modulation of
      the glutamatergic system. We aimed to test this hypothesis further by exploring
      the impact of the alpha4beta2-nicotinic receptor partial agonist varenicline on
      focal and non-focal plasticity, induced by PAS and tDCS, respectively. We
      administered low (0.1 mg), medium (0.3 mg), and high (1.0 mg) single doses of
      varenicline or placebo medication before PAS or tDCS on the left motor cortex of
      25 healthy non-smokers. Corticospinal excitability was monitored by single-pulse
      transcranial magnetic stimulation-induced motor evoked potential amplitudes up to
      36 h after plasticity induction. Whereas low-dose varenicline had no impact on
      stimulation-induced neuroplasticity, medium-dose abolished tDCS-induced
      facilitatory after-effects, favoring focal excitatory plasticity. High-dose
      application preserved cathodal tDCS-induced excitability diminution and focal
      excitatory PAS-induced facilitatory plasticity. These results are comparable to
      the impact of nicotine receptor activation and might help to further explain the
      involvement of specific receptor subtypes in the nicotinic impact on
      neuroplasticity and cognitive functions in healthy subjects and patients with
      neuropsychiatric diseases. 

PMID- 24917273
TI  - A randomized clinical trial comparing methotrexate and mycophenolate mofetil for
      noninfectious uveitis.
AB  - OBJECTIVE: To compare the relative effectiveness of methotrexate and
      mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis,
      or panuveitis. DESIGN: Multicenter, block-randomized, observer-masked clinical
      trial. PARTICIPANTS: Eighty patients with noninfectious intermediate, posterior,
      or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals
      in Madurai and Coimbatore, India. INTERVENTION: Patients were randomized to
      receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate
      mofetil and were monitored monthly for 6 months. Oral prednisone and topical
      corticosteroids were tapered. MAIN OUTCOME MEASURES: Masked examiners assessed
      the primary outcome of treatment success, defined by achieving the following at 5
      and 6 months: (1) <=0.5+ anterior chamber cells, <=0.5+ vitreous cells, <=0.5+
      vitreous haze and no active retinal/choroidal lesions in both eyes, (2) <=10 mg
      of prednisone and <=2 drops of prednisolone acetate 1% a day, and (3) no
      declaration of treatment failure because of intolerability or safety. Additional
      outcomes included time to sustained corticosteroid-sparing control of
      inflammation, change in best spectacle-corrected visual acuity, resolution of
      macular edema, adverse events, subgroup analysis by anatomic location, and
      medication adherence. RESULTS: Forty-one patients were randomized to methotrexate
      and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32
      mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of
      patients achieved treatment success with methotrexate and 47% with mycophenolate
      mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not
      different by treatment arm (P = 0.99). There were no differences between
      treatment groups in time to corticosteroid-sparing control of inflammation (P =
      0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution
      of macular edema (P = 0.31). CONCLUSIONS: There was no statistically significant
      difference in corticosteroid-sparing control of inflammation between patients
      receiving methotrexate or mycophenolate mofetil. However, there was a 22%
      difference in treatment success favoring methotrexate.

PMID- 24917276
TI  - Effect of endurance training on dental erosion, caries, and saliva.
AB  - The aim of this investigation was to give insights into the impact of endurance
      training on oral health, with regard to tooth erosion, caries, and salivary
      parameters. The study included 35 triathletes and 35 non-exercising controls. The
      clinical investigation comprised oral examination, assessment of oral status with
      special regard to caries and erosion, saliva testing during inactivity, and a
      self-administered questionnaire about eating, drinking, and oral hygiene
      behavior. In addition, athletes were asked about their training habits and intake
      of beverages and sports nutrition. For saliva assessment during exercise, a
      subsample of n = 15 athletes volunteered in an incremental running field test
      (IRFT). Athletes showed an increased risk for dental erosion (P = 0.001). No
      differences were observed with regard to caries prevalence and salivary
      parameters measured during inactivity between athletes and controls. Among
      athletes, a significant correlation was found between caries prevalence and the
      cumulative weekly training time (r = 0.347, P = 0.04). In athletes after IRFT and
      at maximum workload, saliva flow rates decreased (P = 0.001 stimulated; P = 0.01
      unstimulated) and saliva pH increased significantly (P = 0.003). Higher risk for
      dental erosions, exercise-dependent caries risk, and load-dependent changes in
      saliva parameters point out the need for risk-adapted preventive dental concepts
      in the field of sports dentistry.

PMID- 24917275
TI  - Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and
      Guidance.
AB  - The function of mature neurons critically relies on the developmental outgrowth
      and projection of their cellular processes. It has long been postulated that the
      neuronal glycoproteins M6a and M6b are involved in axon growth because these four
      transmembrane domain-proteins of the proteolipid protein family are highly
      enriched on growth cones, but in vivo evidence has been lacking. Here, we report
      that the function of M6 proteins is required for normal axonal extension and
      guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon
      tracts was manifested. Most strikingly, the corpus callosum was reduced in
      thickness despite normal densities of cortical projection neurons. In single
      neuron tracing, many axons appeared shorter and disorganized in the double-mutant
      cortex, and some of them were even misdirected laterally toward the subcortex.
      Probst bundles were not observed. Upon culturing, double-mutant cortical and
      cerebellar neurons displayed impaired neurite outgrowth, indicating a cell
      intrinsic function of M6 proteins. A rescue experiment showed that the
      intracellular loop of M6a is essential for the support of neurite extension. We
      propose that M6 proteins are required for proper extension and guidance of
      callosal axons that follow one of the most complex trajectories in the mammalian
      nervous system. 

PMID- 24917277
TI  - [Aortic root replacement with the freestyle stentless bioprosthesis for infective
      endocarditis associated with aortic annular destruction].
AB  - Treatment of infective endocarditis (IE) associated with aortic annular
      destruction remains a formidable surgical challenge. Discussions about the
      optimum modality for reconstruction are still continuing. In such severe
      endocarditis, we have performed aortic root replacement using the Freestyle
      stentless bioprosthesis with the full root technique. From 2005 through 2012, 11
      patients who had aortic valve endocarditis with annular destruction underwent
      aortic root replacement at our institute. All of them were treated with the
      Freestyle stentless bioprosthesis. Their mean age was 69.9 years, and 8 patients
      were men. Two patients had native valve endocarditis and 9 patients had
      prosthetic valve endocarditis. Despite appropriate antibiotic therapy, 3 patients
      required emergency surgery because of hemodynamic deterioration. In-hospital
      death occurred in 1 patient due to progressive hemodynamic failure. The 10
      hospital survivors were followed up for a mean of 27.7+/-23.1 months (range 5 to
      82). Although late death occurred in 2 patients, recurrent IE was not observed in
      any patients during the follow-up. The results of our study suggest that the
      Freestyle stentless bioprosthesis could be an excellent alternative to a
      homograft in the treatment of infective endocarditis associated with aortic
      annular destruction. 

PMID- 24917278
TI  - [Therapeutic use of amiodarone against postoperative fibrillation after cardiac
      surgery].
AB  - We investigated the effect of amiodarone (AMD) administered intravenously for the
      treatment of post-operative atrial fibrillation( POAF) after cardiac surgery.
      After rapid administration of 150 mg for 10 minutes, AMD was administered in 1.0
      mg per minute for 6 hours followed by 0.5 mg per minute for 18 hours. AMD was
      then administered orally 200 mg per day for 1 or 2 weeks. Twenty-five cases were
      enrolled from January 2010 to June 2013. In 18 cases(72%), the patients were
      successfully defibrillated by this protocol. In the other 7 cases, the patients
      required electrical defibrillation, but in 1 patient developed chronic atrial
      fibrillation. It was thought that AMD could be a choice for POAF. 

PMID- 24917279
TI  - [Assessment of traumatic rib fractures caused by traffic accident].
AB  - We reviewed 66 cases of traumatic rib fracture by traffic accident between
      January 2009 and December 2011. The age of patients ranged from 18 to 88 years,
      with an average age of 55.6, and they were predominantly male. They met with
      traffic accident when driving automobiles in 30 cases, driving motorcycles in 15
      cases, and walking in 9 cases. The average number of fractured ribs was 4.1+/
      3.2.Multiple rib fractures were observed in 75.8% of patients. Injuries other
      than rib fractures were involved in all patients who suffered over 7 rib
      fractures. Except one who died of pneumonia 62 days after traffic accident, 7 of
      8 patients died within 48 hours:6 in a shock state and 1 in cardiac pulmonary
      arrest on arrival. About 80 % of the patients with rib fractures were
      hospitalized. As traffic accidents could cause any type of injuries including rib
      fractures, it is important to examine the whole body when patients were
      transported to a hospital. 

PMID- 24917280
TI  - [Outcomes of the surgical treatment of infectious endocarditis in a single
      institute for 13-years].
AB  - Recently, due to the progress in patient managements with antibiotics, the
      prognosis of the active phase infectious endocarditis (IE) has improved, but in
      some cases, urgent or emergent surgical treatment is inevitable because of the
      uncontrollable acute heart failure due to valve regurgitation, uncontrollable
      infection with circulatory collapse, or high embolization risk. We reviewed the
      outcomes of the 57 IE patients who underwent surgical treatment in our hospital
      from January, 2000 to April, 2012. Preoperative state including inflammatory
      responses, bacterial blood culture, antibiotic administration, and surgical
      procedures were examined. No statistical significances were detected in the
      mortalities between elective cases (n=43)and urgent or emergent cases (n=14).
      Totally, mortality was 5.3% including one case in prosthetic valve endocarditis,
      and was satisfactory. 

PMID- 24917281
TI  - [Complete resection of a posterior mediastinal tumor after preoperative
      identification of artery of Adamkiewicz].
AB  - The thoracolumbar spinal cord receives its blood supply primarily from the artery
      of Adamkiewicz (AA), a branch of thoracolumbar intercostal arteries. Aortic cross
      clamping during operation for descending aortic aneurysms can cause paraplegia
      due to spinal cord ischemia secondary to low blood flow through the AA. A 69-year
      old woman was diagnosed with a left posterior mediastinal tumor measuring 66 mm.
      The tumor was adjacent to the thoracic aorta between Th10 to Th12 vertebral
      levels. Preoperative 3-dimensional computed tomography (3D-CT) imaging revealed 2
      AAs originated from the 10th and 11th left intercostal arteries just near the
      tumor. The patient underwent a left thoracotomy and the 2 intercostal arteries
      were carefully dissected from the encapsulated tumor. Complete resection was
      safely achieved with preservation of the AAs. Pathology revealed a schwannoma.
      There were no complications. In performing thoracic surgery for posterior
      mediastinal tumors, it is important to identify the AAs preoperatively and
      preserve them.

PMID- 24917282
TI  - [Long-term survival with complete response by gefitinib treatment followed by
      noncurative operation for lung cancer].
AB  - A 54-year-old man was referred to our hospital because of an abnormal shadow on
      chest X-ray. A computed tomography( CT) scan of the chest revealed a 6.5 cm tumor
      in the right upper lobe suspected of superior vena cava (SVC) infiltration. He
      was diagnosed as lung cancer(adenocarcinoma), and the right upper lobectomy with
      partial resection of SVC was performed. But the pathology confirmed the surgery
      to be non-curative. Nine months after operation, carcinomatous pleuritis was
      detected on chest X-ray. Since deoxyribonucleic acid (DNA)analysis revealed a
      mutation of epidermal growth factor receptor (EGFR) gene in exon 21, gefitinib
      treatment was started. Nine months later, pleural effusion regressed and his
      cerum carcinoembrionic antigen( CEA) level was normalized. 4 years later,
      gefitinib was discontinued by patient's request, however, he is alive without any
      signs of relapse 9 years after the operation.

PMID- 24917283
TI  - [Traumatic hemothorax treated with transcatheter arterial embolization].
AB  - A 33-year-old man was transported to our hospital following a traffic accident.
      He was found to have hemopneumothorax, multiple rib fractures and lung injury by
      computed tomography(CT). Despite thoracic drainage and fluid resuscitation, he
      became hemodynamically unstable. At 2 hours after arrival, CT revealed worsening
      in hemothorax. Emergency angiography of intercostal arteries showed signs of
      hemorrhage from intercostal arteries, and embolization of the 3~6th intercostal
      arteries was performed. After transcatheter arterial embolization(TAE), his vital
      signs got stable and he was discharged without significant complication.

PMID- 24917284
TI  - [Successful management of aorto-esophageal fistula, using staged 3 times
      operation].
AB  - A 66-year-old man, presented with hematemesis and hemorrhagic shock, was
      transported to our institution. Computed tomographic examination suggested a
      pseudo-aneurysm formed by bleeding from aorto-esophageal fistula( AEF). We
      planned staged operations. At first, in an emergent operation, graft replacement
      of descending aorta, was performed under partial cardiopulmonary bypass, by left
      thoracotomy approach. AEF was 5 mm in diameter, and existed inside of normal
      diameter and non-aneurysmal aortic intima. AEF orifice into pseudo-aneurysm was
      closed with aortic wall and was sutured tightly. Next day, gastrointestinal
      fiberscopy was performed, and penetrating ulcer was found at lower esophagus.To
      prevent infective complications, the 2nd operation, subtotal esophagectomy,
      cervical esophagostomy, gastrostomy and tube ileostomy were performed by right
      thoracotomy approach. Post- operative course was uneventful. Two months later,
      3rd operation, cervical esophago-gastric anastomosis was performed, uneventfully.
      Two years and four months elapsed, and no evidences of infection and formation of
      pseudo-aneurysm were observed. 

PMID- 24917285
TI  - [Modified warden procedure for partial anomalous pulmonary venous connection in
      an adult].
AB  - A 46-year-old woman was admitted to our hospital because of congestive heart
      failure and atrial fibrillation. She had undergone atrial septal defect repair at
      the age of 7 years. Computed tomography( CT)scan revealed right upper pulmonary
      vein returned to superior vena cave and the left upper pulmonary vein returned to
      the innominate vein. Cardiac catheterization showed Qp/Qs of 2.6. Pulmonary
      venous drainage repair and right-sided maze procedure was planned. The right
      upper pulmonary vein was led to the left atrium using the modified Warden
      Procedure. The left upper pulmonary vein was divided and anastomosed to the left
      atrial appendage. Concomitantly right-sided maze procedure was performed.
      Postoperative course was uneventful and CT scan revealed no stenosis at
      anastomotic sites. Sinus rhythm was retained and she was discharged on
      postoperative day 30.

PMID- 24917286
TI  - [Total arch replacement for ruptured Stanford type B aortic dissection with
      thrombosed pseudolumen presenting hemodynamic deterioration].
AB  - We report 2 cases of ruptured type B aortic dissection with thrombosed
      pseudolumen presenting hemodynamic deterioration which is a life-threatening
      condition. In such cases, surgical treatment often resulted in high mortality
      rates. We underwent total arch replacement via median sternotomy. In both cases,
      postoperative courses were uneventful. This approach ensured us wider operative
      field to establish cardiopulmonary bypass quickly, and to perform distal
      anastomosis without much difficulty. 

PMID- 24917287
TI  - [Surgical treatment for prosthetic valve endocarditis after aortic root
      replacement].
AB  - Aorto-left ventricular continuity destruction due to prosthetic valve
      endocarditis is rare, but it is one of the fatal complications after aortic root
      operation. We report a case of surgical treatment for prosthetic valve
      endocarditis after aortic root replacement. A 47-year-old man, who had undergone
      aortic root replacement with a composite graft was transferred to our hospital
      with sudden chest pain and high fever. Enhanced computed tomography showed a
      large space with contrast enhancement suggesting perivalvular leakage around the
      artificial composite graft. Emergency operation including aortic root re
      replacement and reconstruction of the left ventricular outflow tract was
      performed successfully. We focused on its technical aspect. 

PMID- 24917288
TI  - [Adenocarcinoma with cavity formation caused by check valve mechanism].
AB  - A 63-year-old male who has a chief complaint of dyspnea on effort was admitted to
      our hospital because of abnormal chest computed tomography (CT). Chest CT showed
      a thin-walled cavity in the left lower lung that was 40 mm in diameter, and local
      high density shadow near the cavity. The tumor was resected and diagnosed as
      adenocarcinoma. The pathogenesis of the thin-wlled cavity formation in this case
      was considered to be caused by check valve mechanism. 

PMID- 24917289
TI  - [Mitral valve repair for mitral regurgitation induced by infective endocarditis
      complicated with ulcerative colitis; report of a case].
AB  - Infective endocarditis is a rare complication of ulcerative colitis. We report on
      a 22-year-old man, who had been treated of ulcerative colitis for 5 years. He
      presented with dyspnea on effort. In spite of medical treatment, he developed
      congestive heart failure. Transthoracic echocardiography showed a large
      perforation on the anterior leaflet of the mitral valve, and prolapses of the
      posterior leaflet of the mitral valve with rupture of the chordae. The patient
      underwent mitral valve repair with an autologous pericardial patch on the
      anterior leaflet combined with butterfly resection and suture of the posterior
      leaflet. The postoperative course was uneventful. 

PMID- 24917290
TI  - [Penetrating injury of the left ventricle caused by a nail gun; report of a
      case].
AB  - Penetrating cardiac injuries are life-threatening emergencies. We present a case
      of a 24-year-old construction worker who accidentally shot himself with a nail
      gun. Chest X-ray showed a 6 cm-long nail overlapping the cardiac shadow. A
      computed tomography (CT) scan revealed the nail penetrating the left ventricle
      and a large amount of pericardial effusion. Median sternotomy was performed and
      cardiopulmomary bypass was established. Then, the nail was removed and the left
      ventricular wound was repaired by 4-0 Prolene mattress sutures buttressed with
      felt-strips. He had an uncomplicated postoperative course and was discharged 7
      days postoperatively. 

PMID- 24917292
TI  - [Left ventriculoplasty in a patient with suspected takotsubo cardiomyopathy
      followed by a left ventricular aneurysm].
AB  - A 42-year-old woman was admitted with chest pain. Coronary angiography did not
      reveal any significant stenosis, but left ventriculography showed akinesis and
      ballooning of the apex with a hyperkinetic basal segment indicating Takotsubo
      cardiomyopathy. Cerebral embolism occurred after one and a half years because of
      a left ventricular thrombus. The apical akinesis had worsened to a left
      ventricular aneurysm (maximum diameter 43 mm). The left ventricle was
      reconstructed to avoid repeated thrombus formation and cerebral infarction
      despite anticoagulant therapy. A pathological assessment revealed a fibrotic
      myocardium, but the cause of the cardiac aneurysm remained unknown. Although the
      outcome of Takotsubo cardiomyopathy is relatively good, careful observation and
      appropriate treatment are needed considering the possibility of aggravation. 

PMID- 24917291
TI  - [Acute type A aortic dissection with Birt-Hogg-Dube syndrome; report of a case].
AB  - We describe a 76-year-old woman with cardiac tamponade who was admitted to our
      hospital. She underwent ascending and partial arch aortic replacement to treat
      acute type A aortic dissection. However, postoperative respiratory failure
      developed and a chest X-ray revealed right lung pneumothorax. The lung was
      finally expanded after difficulties with prolonged tube drainage. Chest computed
      tomography(CT) showed multiple cystic changes in the bilateral lungs. Her sister
      and her daughter also had a history of spontaneous pneumothorax. We finally
      diagnosed Birt-Hogg-Dube syndrome after deoxyribonucleic asid(DNA)sequencing of
      folliculin( FLCN) gene. 

PMID- 24917293
TI  - [Malignant peripheral nerve sheath tumor causing hemothorax; report of a case].
AB  - We herein report a case of malignant peripheral nerve sheath tumor that caused a
      hemothorax. A 39-year-old male was found to have an abnormal shadow on a chest X
      ray. Chest computed tomography showed a 60-mm tumor in the right posterior
      mediastinum. Fourteen months earlier, he underwent drainage of a hemothorax with
      a medaistinal tumor but refused to undergo further examinations. We performed a
      tumor resection combined with the right lower lobectomy and the partial resection
      of the pericardium because of invasion. The histological examination confirmed
      the diagnosis of a malignant peripheral nerve sheath tumor. Postoperative
      radiotherapy was performed. The patient has been well without recurrence for 9
      months. 

PMID- 24917294
TI  - [Hemothorax complicated with celiac artery compression syndrome (CACS); report of
      a case].
AB  - We report a case of hemothorax complicated with celiac artery compression
      syndrome (CACS). A 43-year-old man presented with a sudden onset left back pain.
      Computed tomography (CT) showed its hemothorax, esophageal artery aneurysm and
      severe stenosis of the celiac truncus with its anterior compression by median
      accurate ligament, and a diagnosis of CACS associated with rupture of the
      aneurysm was made. Emergent transcatheter arterial embolization of the aneurysm
      resulted in a technical failure, although the patient's condition was stable and
      performed esophageal artery ligation through video-assisted thoracoscopic surgery
      on day 5 after onset. After surgery, the patient recovered without significant
      incidents. A cause of this aneurysmal development was supposed to be a
      significantly increased esophageal arterial blood flow with its luminal dilation
      to compensate a decreased celiac blood flow. Segmental arterial mediolysis could
      not be excluded as another cause. 

PMID- 24917295
TI  - Evolution of repeat prostate biopsy strategies incorporating transperineal and
      MRI-TRUS fusion techniques.
AB  - PURPOSE: To test the hypothesis that MRI-TRUS fusion technique can increase the
      detection rate of prostate cancer (PC) in patients with previously negative
      biopsy. METHODS: Patient records of men with persisting suspicion for PC after
      previous negative biopsy having undergone either extensive transrectal prostate
      biopsies (MD Anderson protocol; MDA), transperineal saturation (STP) or magnetic
      resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion transperineal
      biopsies (MTTP) in three consecutive time intervals were reviewed
      retrospectively. The respective approach was the standard for the above
      indication at these episodes. In Cambridge, 70 patients underwent MDA biopsies,
      75 STP underwent biopsies and 74 patients underwent MTTP biopsies. In total, 164
      MTTP patients with the same indication from Heidelberg were analysed as reference
      standard. In total, 383 men were included into analysis. Low-grade PC was defined
      as Gleason score 7 (3 + 4) or lower. RESULTS: Even though MTTP patients had
      significantly larger prostates, the overall cancer detection rate for PC was the
      highest in MTTP (24.2 % MDA, 41.3 % STP, 44.5 % MTTP, p = 0.027, Kruskal-Wallis
      test). The detection rate for clinically relevant high-grade PC was highest in
      MTTP; however, this did not reach statistical significance compared with MDA
      (23.5 % MDA, 12.9 % STP, 27.2 % MTTP, p = 0.25, Fischer's exact test). Comparing
      MTTP between Cambridge and Heidelberg, detection rates did not differ
      significantly (44.5 vs. 48 %, p = 0.58). There was a higher detection rate of
      high-grade cancer in Heidelberg. (36.3 vs. 27.2 %, p = 0.04). CONCLUSION:
      Patients whom are considered for repeat biopsies may benefit from undergoing MRI
      targeted TRUS fusion technique due to higher cancer detection rate of significant
      PC.

PMID- 24917296
TI  - The schooling of offspring and the survival of parents.
AB  - Contemporary stratification research on developed societies usually views the
      intergenerational transmission of educational advantage as a one-way effect from
      parent to child. However, parents' investment in their offspring's schooling may
      yield significant returns for parents themselves in later life. For instance,
      well-educated offspring have greater knowledge of health and technology to share
      with their parents and more financial means to provide for them than do their
      less-educated counterparts. We use data from the 1992-2006 Health and Retirement
      Study (HRS) to examine whether adult offspring's educational attainments are
      associated with parents' survival in the United States. We show that adult
      offspring's educational attainments have independent effects on their parents'
      mortality, even after controlling for parents' own socioeconomic resources. This
      relationship is more pronounced for deaths that are linked to behavioral factors:
      most notably, chronic lower respiratory disease and lung cancer. Furthermore, at
      least part of the association between offspring's schooling and parents' survival
      may be explained by parents' health behaviors, including smoking and physical
      activity. These findings suggest that one way to influence the health of the
      elderly is through their offspring. To harness the full value of schooling for
      health, then, a family and multigenerational perspective is needed. 

PMID- 24917297
TI  - G-protein-coupled receptors and localized signaling in the primary cilium during
      ventral neural tube patterning.
AB  - The primary cilium is critical in sonic hedgehog (Shh)-dependent ventral
      patterning of the vertebrate neural tube. Most mutants that cause disruption of
      the cilium result in decreased Shh signaling in the neural tube. In contrast,
      mutations in the intraflagellar complex A (IFT-A) and the tubby family protein,
      Tulp3, result in increased Shh signaling in the neural tube. Proteomic analysis
      of Tulp3-binding proteins first pointed to the role of the IFT-A complex in
      trafficking Tulp3 into the cilia. Tulp3 directs trafficking of rhodopsin family G
      protein-coupled receptors (GPCRs) to the cilia, suggesting the role of a GPCR in
      mediating the paradoxical effects of the Tulp3/IFT-A complex in causing increased
      Shh signaling. Gpr161 has recently been identified as a Tulp3/IFT-A-regulated
      GPCR that localizes to the primary cilium. A null knock-out mouse model of Gpr161
      phenocopies Tulp3 and IFT-A mutants, and causes increased Shh signaling
      throughout the neural tube. In the absence of Shh, the bifunctional Gli
      transcription factors are proteolytically processed into repressor forms in a
      protein kinase A (PKA) -dependent and cilium-dependent manner. Gpr161 activity
      results in increased cAMP levels in a Galphas -coupled manner, and determines
      processing of Gli3. Shh signaling also results in removal of Gpr161 from the
      cilia, suggesting that Gpr161 functions in a positive feedback loop in the Shh
      pathway. As PKA-null and Galphas mutant embryos also exhibit increased Shh
      signaling in the neural tube, Gpr161 is a strong candidate for a GPCR that
      regulates ciliary cAMP levels, and activates PKA in close proximity to the cilia.

PMID- 24917298
TI  - The role of zinc in the stability of the marginally stable IscU scaffold protein.
AB  - Understanding the factors that determine protein stability is interesting because
      it directly reflects the evolutionary pressure coming from function and
      environment. Here, we have combined experimental and computational methods to
      study the stability of IscU, a bacterial scaffold protein highly conserved in
      most organisms and an essential component of the iron-sulfur cluster biogenesis
      pathway. We demonstrate that the effect of zinc and its consequence strongly
      depend on the sample history. IscU is a marginally stable protein at low ionic
      strength to the point that undergoes cold denaturation at around -8 degrees C
      with a corresponding dramatic decrease of enthalpy, which is consistent with the
      fluxional nature of the protein. Presence of constitutively bound zinc
      appreciably stabilizes the IscU fold, whereas it may cause protein aggregation
      when zinc is added back posthumously. We discuss how zinc coordination can be
      achieved by different side chains spatially available and all competent for
      tetrahedral coordination. The individual absence of some of these residues can be
      largely compensated by small local rearrangements of the others. We discuss the
      potential importance of our findings in vitro for the function in vivo of the
      protein. 

PMID- 24917299
TI  - Predicting Australian adults' sun-safe behaviour: examining the role of personal
      and social norms.
AB  - OBJECTIVES: To address the scarcity of comprehensive, theory-based research in
      the Australian context, this study, using a theory of planned behaviour (TPB)
      framework, investigated the role of personal and social norms to identify the key
      predictors of adult Australians' sun-safe intentions and behaviour. DESIGN: The
      study used a prospective design with two waves of data collection, 1 week apart.
      METHODS: Participants were 816 adults (48.2% men) aged between 18 and 88 years
      recruited from urban, regional, and rural areas of Australia. At baseline,
      participants completed a questionnaire assessing the standard TPB predictors
      (attitude, subjective norm, and perceived behavioural control [PBC]), past
      behaviour, behavioural intention, and additional measures of group norm for the
      referent groups of friends and family, image norm, personal norm, personal
      choice/responsibility, and Australian identity. Seventy-one per cent of the
      participants (n = 577) reported on their sun-safe behaviour in the subsequent
      week. RESULTS: Via path modelling, past behaviour, attitude, group norm
      (friends), personal norm, and personal choice/responsibility emerged as
      independent predictors of intentions which, in turn, predicted sun-safe behaviour
      prospectively. Past behaviour, but not PBC, had direct effects on sun-safe
      behaviour. The model explained 61.6% and 43.9% of the variance in intention and
      behaviour, respectively. CONCLUSIONS: This study provides support for the use of
      a comprehensive theoretical decision-making model to explain Australian adults'
      sun-safe intentions and behaviours and identifies viable targets for health
      promoting messages in this high-risk context. Statement of contribution What is
      already known on this subject? Identifying determinants of sun-safe behaviour is
      vital in high-risk cancer areas like Australia. For young Australians, friendship
      group norm is a key influence of intentions and behaviour. Little is known about
      drivers of sun safety, especially norms, among Australian adults in general. What
      does this study add? This study drew on qualitative data and reconceptualized
      norms for Australians' sun-safe decisions. Friendship group norm and personal
      norm, not family group norm, influence sun-safe intentions. Perceived
      responsibility and choice to be sun safe also impact on people's intentions.

PMID- 24917301
TI  - Endocannabinoids: a protective receptor pool.

PMID- 24917300
TI  - Grid cells and cortical representation.
AB  - One of the grand challenges in neuroscience is to comprehend neural computation
      in the association cortices, the parts of the cortex that have shown the largest
      expansion and differentiation during mammalian evolution and that are thought to
      contribute profoundly to the emergence of advanced cognition in humans. In this
      Review, we use grid cells in the medial entorhinal cortex as a gateway to
      understand network computation at a stage of cortical processing in which firing
      patterns are shaped not primarily by incoming sensory signals but to a large
      extent by the intrinsic properties of the local circuit. 

PMID- 24917306
TI  - Effects of metformin on endometrial cancer cell growth in vivo: a preoperative
      prospective trial.
AB  - BACKGROUND: Metformin, an antidiabetic drug, decreases the incidence of various
      cancers in diabetic patients. Metformin-induced inhibition of cancer cell
      proliferation has been confirmed in vitro but not in humans. Because endometrial
      cancer is associated with insulin resistance, the authors investigated whether a
      diabetes-therapeutic metformin dose inhibits cancer cell growth in patients with
      endometrial cancer. METHODS: A dose of metaformin was administered (1500-2250
      mg/day) to 31 patients with endometrial cancer preoperatively for 4 to 6 weeks.
      Cell proliferation was assessed in patient tissues using immunohistochemical and
      Western blot analyses and DNA synthesis was measured in serum using a thymidine
      uptake assay. All statistical tests were 2-sided. P values of < .05 were
      considered statistically significant. RESULTS: Preoperative metformin treatment
      decreased DNA synthesis in sera and significantly reduced the Ki-67 (mean
      proportional decrease, 44.2%; 95% confidence interval [95% CI], 35.4-53.0 [P <
      .001]) and topoisomerase IIalpha (mean proportional decrease, 36.4%; 95% CI, 26.7
      46.0 [P < .001]) labeling indices. Levels of phospho-ribosomal protein S6 and
      phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) were found to be
      significantly decreased and phospho-adenosine monophosphate-activated protein
      kinase and p27 levels were significantly increased. Preoperative metformin use
      caused significant decreases in circulating factors, including insulin, glucose,
      insulin-like growth factor 1, and leptin. DNA synthesis-stimulating activity in
      patient sera was significantly decreased during metformin administration.
      CONCLUSIONS: An antidiabetic dose of metformin inhibited endometrial cancer cell
      growth in vivo, an effect likely due to its effect on humoral factor(s). This
      translational study provides considerable rationale to initiate large clinical
      trials.

PMID- 24917305
TI  - Light as a central modulator of circadian rhythms, sleep and affect.
AB  - Light has profoundly influenced the evolution of life on earth. As widely
      appreciated, light enables us to generate images of our environment. However,
      light - through intrinsically photosensitive retinal ganglion cells (ipRGCs) -
      also influences behaviours that are essential for our health and quality of life
      but are independent of image formation. These include the synchronization of the
      circadian clock to the solar day, tracking of seasonal changes and the regulation
      of sleep. Irregular light environments lead to problems in circadian rhythms and
      sleep, which eventually cause mood and learning deficits. Recently, it was found
      that irregular light can also directly affect mood and learning without producing
      major disruptions in circadian rhythms and sleep. In this Review, we discuss the
      indirect and direct influence of light on mood and learning, and provide a model
      for how light, the circadian clock and sleep interact to influence mood and
      cognitive functions. 

PMID- 24917307
TI  - Associations among survivorship care plans, experiences of survivorship care, and
      functioning in older breast cancer survivors: CALGB/Alliance 369901.
AB  - PURPOSE: Survivorship care plans (SCP) are recommended for all cancer patients
      and could be especially useful to survivors 65 years and over ("older"). This
      study examined receipt of SCPs among older breast cancer survivors and whether
      SCPs were associated with improved patient-reported outcomes. METHODS: Three
      hundred and twenty-eight older women diagnosed with invasive, nonmetastatic
      breast cancer between 2007-2011 were recruited from 78 cooperative-group sites.
      Participants completed telephone interviews at baseline and 1-year posttreatment.
      Regression analyses examined SCP receipt (yes/no) and functioning (EORTC-QLQ
      C30), cancer worry, and experiences of survivorship care (care coordination,
      knowledge). RESULTS: Only 35% of women received SCPs. For each 1-year increase in
      age, there was a 5% lower odds of receiving an SCP (odds ratio (OR) = 0.94, 95%
      confidence interval (CI) 0.91-0.98, p = 0.007). Besides age, no other factor
      predicted SCPs. SCP receipt was associated with greater knowledge and
      understanding of requisite follow-up care (p < 0.05); however, functioning was
      not significantly different among those with vs. without SCPs. CONCLUSIONS:
      Receipt of care plans was limited. SCPs improved understanding of breast cancer
      follow-up care among older survivors, but did not impact functioning one year
      post-treatment. IMPLICATIONS FOR CANCER SURVIVORS: To impact functioning and
      salient needs of the growing cohort of older survivors, survivorship care plans
      likely should be tailored to geriatric-specific issues. To improve functioning,
      SCP content should expand to include exercise, nutrition, polypharmacy, social
      support and management of symptom burden from cancer, and other comorbid
      conditions. To improve follow-up care for cancer survivors, SCPs should delineate
      shared care roles between oncology and primary care in managing recurrence
      surveillance, screening, and cancer sequelae.

PMID- 24917309
TI  - A minimally invasive treatment option for large metastatic brain tumors: long
      term results of two-session Gamma Knife stereotactic radiosurgery.
AB  - BACKGROUND: Large brain metastases (BM) remain a significant cause of morbidity
      and death for cancer patients despite current advances in multimodality
      therapies. The goal of the present study was to evaluate the efficacy and
      limitations of 2-session Gamma Knife stereotactic radiosurgery (SRS) for patients
      with large BM. METHODS: This is a prospective, open-label and single arm study
      analyzing 58 consecutive patients who received 2-session SRS for large BM (>= 10
      mL). The median age was 66 years, and the median Karnofsky performance status
      (KPS) score was 70. SRS was the initial treatment in 51 large tumors (84%) and
      was used as salvage after failed prior treatments for 10 tumors (16%). The
      fraction protocol was 20-30 Gy given in 2 fractions with 3-4 weeks between
      fractions. Overall survival (OS) and neurological death (ND), local tumor control
      and KPS were analyzed. RESULTS: The median follow-up time was 9.0 months. One-
      and 2-year OS rates were 47% and 20%, respectively. The median OS time was 11.8
      months (95% CI: 5.5-15.6). The causes of death were intracranial local
      progression in 5 cases, meningeal carcinomatosis in 3 and progression of the
      primary lesion in 39. One- and 2-year ND-free survival rates were 91% and 84%,
      respectively. In 52 of 61 large BM (85%) with sufficient radiological follow-up
      data, 6- and 12-month local tumor control rates were 85% and 64%, respectively.
      The mean KPS improved from 70 at the 1st SRS to 82 at the 2nd; the first follow
      up mean KPS was 87 (P < 0.001). Symptomatic radiation injury developed and
      required conservative treatment in 3 patients (5%). CONCLUSIONS: Long-term follow
      up showed that two-session Gamma Knife SRS achieved durable tumor control rates
      as well as acceptable treatment-related morbidity. This treatment method may
      potentially merit being offered to patients with large BM who are in poor
      condition or are otherwise ineligible for standard care.

PMID- 24917311
TI  - Isolation and screening of probiotic candidates from marron, Cherax cainii
      (Austin, 2002) gastrointestinal tract (GIT) and commercial probiotic products for
      the use in marron culture.
AB  - Six strains of bacteria including Bacillus mycoides (A10) and Shewanella species
      (A12) isolated from healthy marron intestine, Bacillus species (PM1), Bacillus
      subtilis (PM3), Bacillus sp. (PM4) and Bacillus sp. (AQ) from commercial
      probiotic products were investigated for probiotic potential in marron culture.
      Antibiotic susceptibility tests indicated PM3 and PM4 were susceptible to all
      nine antibiotics evaluated. A10, A12 and AQ were resistant to class penicillins,
      whereas PM1 was resistant to class penicillin and macrolides. All strains were
      non-pathogenic for marron. Strong inhibition against Vibrio mimicus and Vibrio
      cholerae non-01 was exhibited by PM4 and PM3. A10 inhibited V. mimicus at 72 h of
      growth, but not V. cholerae non-01, whereas A12 inhibited V. cholerae non-01 but
      not V. mimicus, and AQ showed no inhibition activity. A wide range of enzymes
      were produced by A10 and AQ using the API ZYM test. Protease enzymes were
      produced by PM3, PM4, AQ and PM1. In order of effectiveness, the following
      bacteria have probiotic potential: B. subtilis (PM3), Bacillus sp. (PM4) and B.
      mycoides (A10). Further study is required to determine the bacterium or any
      combination that gives a multibeneficial effect on marron. 

PMID- 24917310
TI  - Comparative functional anatomy of the epaxial musculature of dogs (Canis
      familiaris) bred for sprinting vs. fighting.
AB  - The axial musculoskeletal system of quadrupedal mammals is not currently well
      understood despite its functional importance in terms of facilitating postural
      stability and locomotion. Here we examined the detailed architecture of the
      muscles of the vertebral column of two breeds of dog, the Staffordshire bull
      terrier (SBT) and the racing greyhound, which have been selectively bred for
      physical combat and high speed sprint performance, respectively. Dissections of
      the epaxial musculature of nine racing greyhounds and six SBTs were carried out;
      muscle mass, length, and fascicle lengths were measured and used to calculate
      muscle physiological cross-sectional area (PCSA), and to estimate maximum muscle
      potential for force, work and power production. The longissimus dorsi muscle was
      found to have a high propensity for force production in both breeds of dog;
      however, when considered in combination with the iliocostalis lumborum muscle it
      showed enhanced potential for production of power and facilitating spinal
      extension during galloping gaits. This was particularly the case in the
      greyhound, where the m. longissimus dorsi and the m. iliocostalis lumborum were
      estimated to have the potential to augment hindlimb muscle power by ca. 12%.
      Breed differences were found within various other muscles of the axial
      musculoskeletal system, particularly in the cranial cervical muscles and also the
      deep muscles of the thorax which insert on the ribs. These may also highlight key
      functional adaptations between the two breeds of dog, which have been selectively
      bred for particular purposes. Additionally, in both breeds of dog, we illustrate
      specialisation of muscle function by spinal region, with differences in both mass
      and PCSA found between muscles at varying levels of the axial musculoskeletal
      system, and between muscle functional groups.

PMID- 24917312
TI  - Suspected acorn toxicity in nine horses.
AB  - REASONS FOR PERFORMING STUDY: Acorn toxicity has been anecdotally reported to
      cause fatal colitis and colic in horses but reports in the scientific literature
      are sparse. OBJECTIVES: This study reports the diagnosis, treatment, prognosis
      and outcome of 9 cases with suspected acorn toxicity admitted to 2 referral
      hospitals. STUDY DESIGN: Retrospective case series. METHODS: Case records from
      2004 to 2013 were reviewed. Horses were included in the study if they met 3 of 4
      criteria: exposure to acorns; clinical and laboratory data suggesting alimentary
      or renal dysfunction; acorn husks in the faeces or gastrointestinal tract; and
      necropsy and histopathological findings consistent with acorn toxicity. Data
      collected included case history, clinical presentation, clinicopathological data,
      ultrasonographic findings, case progression, and necropsy and histopathological
      findings. RESULTS: Nine horses met the inclusion criteria. Five cases presenting
      with haemorrhagic diarrhoea deteriorated rapidly and were subjected to euthanasia
      or died. Four cases showed signs of colic with gas distension, displacement of
      the large colon and diarrhoea. Three of these (33%) survived with medical
      management, the fourth was subjected to euthanasia. Post mortem examination of 6
      cases demonstrated submucosal oedema of the large intestine and caecum (n = 6),
      acute tubular nephrosis (n = 6), diffuse necrohaemorrhagic and ulcerative
      typhlocolitis and enteritis (n = 4), and small intestinal oedema (n = 3).
      CONCLUSIONS: Acorn ingestion may be associated with typhylocolitis leading to
      diarrhoea, colic and acute renal tubular nephrosis. Recovery is possible in
      mildly affected cases; more severe cases show hypovolaemia, intractable pain,
      renal dysfunction and cardiovascular failure, and often succumb to the disease
      process. Disease is only seen in a small proportion of the population exposed to
      acorns and there seems to be an increased occurrence in certain years. Further
      investigation into factors predisposing to disease is required, but limiting
      exposure to acorns in the autumn seems prudent.

PMID- 24917314
TI  - [Not Available].

PMID- 24917315
TI  - Remission, prediction and stability of symptoms in schizophrenia: A naturalistic
      12-month follow-up study.
AB  - Abstract Objective. Since its introduction in 2005, schizophrenia remission
      consensus criteria have been used in several prospective and cross-sectional
      studies. The aim of this prospective assessment of patients with schizophrenia
      was to employ the remission criteria in a naturalistic study design. Methods. One
      hundred and six patients with schizophrenia (ICD10 F 20.x) were enrolled into the
      study during inpatient treatment. Remission criteria with respect to changes in
      psychopathology ratings were obtained by trained interviewers at discharge and at
      12-month follow-up using BPRS. Furthermore, information on social functioning and
      treatment-related quality of life were assessed using GAF (Global Assessment of
      Functioning) and SWN-K (Subjective Wellbeing under Neuroleptic Treatment Scale).
      Results. A total of 13.2% of the patients were found to meet remission criteria
      during follow-up. While there was no significant change in the mean BPRS scores,
      14.2% of the subjects showed significant worsening and 29.2% significant
      improvement of their psychotic symptoms. Subsequent logistic regression analysis,
      explaining approximately 32% of symptomatic remission variance, indicated a
      significant influence of BPRS-Overall-Score and independent living at discharge.
      Conclusions. The results of this naturalistic study indicate that only a minority
      of former inpatients with schizophrenia achieve remission after 1 year and
      relevant subgroups of patients have significant bi-directional changes in
      symptoms during follow-up. 

PMID- 24917316
TI  - Demographic and clinical characteristics of users of psychiatric emergency
      services on an off-shore island in Taiwan.
AB  - Abstract Objective. This study assessed the socio-demographic and clinical
      characteristics of psychiatric emergency service (PES) patients treated in a
      hospital on an off-shore island of Taiwan. Method. Data were gathered on 472
      identified psychiatric patients presenting to PES over a 4-year period. Results.
      The majority of patients were male and were in the 50-59 age group with no
      previous psychiatric treatment or family history of mental illness.
      Hospitalization rates were low for both genders, but males spent a longer time in
      the emergency department. Males were more often seen for violence and homicidal
      behaviours, while females showed more evidence of suicidal behaviour. Males were
      more likely to receive medication by injection with or without physical restraint
      as opposed to oral medication and emotional support. Conclusions. The clinical
      characteristics of male and female PES patients in this remote island showed
      differences in length of stay, psychiatric diagnoses, behaviour characteristics,
      and final disposition. These findings differ from those in studies of PES
      patients on the main island of Taiwan, the United States and Europe. Future
      studies of other remote areas may confirm these findings and highlight the need
      to provide more and particular mental health services to these underserved areas.

PMID- 24917317
TI  - Development of the Screener for Assessing Depression Scale: Why do we need
      another depression scale?*.
AB  - Abstract Depression is a significant problem which affects the lives of a
      substantial number of people. Improved recognition of depression is an important
      step towards the treatment and prevention of depression. Objective. The present
      study examined the reliability and validity of the Screener for Assessing
      Depression (SAD) Scale as a measure of depression severity and as a confirmation
      of a major depressive episode. Method. The sample included 100 adults who were
      receiving inpatient psychiatric treatment (60 met criteria for a major depressive
      disorder and 40 met criteria for other psychological disorders without depression
      as a main feature). Results. Different cut-off scores were proposed in order to
      score the SAD Scale as a screening measure or to confirm a depressive episode.
      Scoring the SAD Scale according to the criteria for a major depressive episode
      correctly classified 87% of the sample. Conclusion. Overall, the results
      indicated that the SAD Scale is a reliable and valid measure for detecting a
      depressive episode and for assessing depression severity. 

PMID- 24917318
TI  - Development of a structured interview schedule to assess stage of psychological
      recovery from enduring mental illness.
AB  - Abstract Objective. To develop a brief interview-based assessment tool, feasible
      for routine use in mental health service settings to measure an individual's
      stage of psychological recovery from an enduring mental illness. Method. Key
      indicators for each stage of psychological recovery were formulated according to
      the stages of psychological conceptual framework and an analysis of transcribed
      data wherein 17 consumer participants described their illness and recovery
      experiences. Upon development of the measure, Short Interview to assess Stages of
      Recovery (SIST-R), the instrument was evaluated by practitioners and consumers to
      examine its feasibility for use in mental health service settings. A pilot test
      with 18 mental health consumer participants compared results obtained by the SIST
      R with those from an existing self-report stages of psychological recovery
      measure (STORI), a measure of psychological distress (K-10), and a measure of
      recovery (RAS). Results. Concordance between the SIST-R and the STORI was
      substantial (Somers' D = 0.61, P = 0.004). The mean scores from other recovery
      measures correspond with what could be theoretically expected across individual
      stages of recovery. Conclusion. This study contributes towards the strengthening
      of a recovery-oriented approach within clinical/mental health service settings
      with the development of an assessment tool that demonstrates potential clinical
      utility. There is a need to validate further the preliminary findings of this
      study. 

PMID- 24917319
TI  - How do people with body dysmorphic disorder view themselves? A thematic analysis.
AB  - Abstract Objectives. To examine the accounts of people with body dysmorphic
      disorder (BDD) and qualitatively explore self perceptions. Methods. Eleven people
      with BDD were interviewed using a semi-structured schedule. Participants brought
      photographs of themselves and drew a self-portrait. Transcribed interviews were
      analysed using a thematic analysis. Results. The most common theme was increased
      threat perception resulting in disordered interpersonal relationships. Other
      themes included the wish for regularity and symmetry in appearance, an idealised
      childhood self, the duty to look good, and a focus on specific "defective"
      features rather than general ugliness. Conclusions. Using thematic analysis and
      visual methods, we identified core themes that appear to characterise the way
      individuals with BDD perceive themselves and their interpersonal relationships.
      Thematic analysis offers promise as a tool to explore the overlap between BDD and
      other putatively related mental health problems. 

PMID- 24917320
TI  - Prevalence, pattern and impact of depression on quality of life of stroke
      survivors.
AB  - Abstract Objective. This study documented the incidence, pattern and impact of
      depression on QoL of stroke-survivors within 6-month post-stroke. Methods. This
      study involved 65 stroke survivors consecutively recruited at ictus from a
      tertiary health institution in Nigeria. The National Institute of Health Stroke
      Scale, Stroke-Specific Quality-of-Life (SSQOL), international classification of
      diseases (tenth edition) and Center for Epidemiological Scale-Depression (CES-D)
      were administered at ictus to assess stroke-severity, QoL and depression
      respectively. The SSQOL, ICD-10 and CES-D were subsequently administered every
      other week for 6 months. Data were treated using Spearman's correlation
      coefficient, Mann-Whitney U-test and multivariable stepwise linear regression
      analysis (P=0.05). Results. Participants were age 58.1+/-15.7 years; 38 and 27
      hemorrhagic and ischaemic stroke respectively. Twenty-six (40%) and 60.0% had
      moderate and severe stroke, respectively. The QoL at post-stroke periods were
      significantly influenced (P<0.05) by depression, age, marital status, spouse
      supports, stroke-severity, and educational-attainment. Depression determined
      (P<0.05) poor QoL in stroke-survivors. Co-morbidity with stroke severity was a
      determinant (P<0.05) of poor QoL and death. The haemorrhagic stroke survivors had
      significantly higher (P<0.05) QoL at post-stroke periods. Conclusion. Depression
      is associated with stroke. It is common within the first 6 months post-stroke and
      has negative impact on quality of life of stroke-survivors. 

PMID- 24917321
TI  - The importance of systematic genetic approach to familial schizophrenia cases and
      discussion of cryptic mosaic X chromosome aneuploidies in schizophrenia
      pathogenesis.
AB  - Abstract Objective. The aim of this study is to contribute to the understanding
      of schizophrenia genetics by using efficient algorithmic examination techniques
      including dysmorphic examination, karyotyping, and Fluoresence in situ
      hybridization (FISH). Methods. In this study we have investigated 20 familial
      schizophrenia patients from Turkey who had an affected first-degree relative.
      Dysmorphic examination of the schizophrenia cases and their relatives have been
      performed. High resolution banding (HRB), specific centromeric, subtelomeric and
      22q11.2 region FISH probes were used for genotyping of patients. Results.
      Dysmorphic examination revealed ear, palate, nose, columella anomalies, and
      obesity in contributing patients, and the pale skin was noticed. The medical
      histories and clinical findings of two schizophrenia twins were almost identical.
      HRB study demonstrated the presence of 46,XX[55]/47,XXX[4]/48,XXXX[1]
      constitution in a paranoid schizophrenia case and 46,XX[67]/45,X[5] karyotype in
      her mother. FISH studies aiming subtelomeric chromosomal regions revealed no
      rearrangements and 22q11.2 regions were intact in all of the patients.
      Conclusions. The parental gonadal mosaicism lying at the origin of the mitotic
      aneuploidy may be the reason for mosaic X chromosome aneuploidies in our mother
      daughter schizophrenia couple. Mosaic X chromosome aneuploidies may accompany
      schizophrenia cases and may contribute to pathogenesis of familial schizophrenia.

PMID- 24917322
TI  - Drug-drug interactions in general hospital and psychiatric hospital in-patients
      prescribed psychotropic medications.
AB  - Abstract Objectives. Drug-drug interactions (DDIs) present a serious, ever
      increasing clinical problem. Previous studies identified DDIs among psychiatric
      inpatients prescribed psychotropics, but none have focused on psychotropics
      prescribed to General Hospital inpatients. This study aimed to identify: putative
      drug-drug interactions; mechanisms; potential seriousness among patients
      prescribed psychotropes in both psychiatric and general hospital inpatients
      settings. We hypothesised that potential interactions per person would be greater
      in General Hospital inpatients on psychotropics, due to polypharmacy. Method. We
      surveyed psychotropic prescribing in hospital wards in a public sector mental
      health organisation and a 500-bed general hospital. Ward pharmacists collected
      drug prescription data. A computer based protocol evaluated DDIs. Results. A
      total of 7.4% of General Hospital inpatients and 100% of Psychiatric Unit
      inpatients surveyed were prescribed psychotropic medication. The General Hospital
      group had significantly more potential interactions per person (3.0) than
      Psychiatric inpatients (1.3) (P<0.05). There were significantly more potentially
      serious interactions in the general hospital group (P<0.025). Conclusions. DDIs
      affect those prescribed psychotropics in both General and Psychiatric Hospitals.
      The General Hospital patients had a higher number per person and more serious
      potential interactions, yet are often poorly served by psychiatric services,
      suggesting that liaison psychiatrists have a role in physician education and DDI
      assessment. 

PMID- 24917323
TI  - A close correlation between plasma and serum levels of brain-derived neurotrophic
      factor (BDNF) in healthy volunteers.
AB  - Abstract Objective. Brain-derived neurotrophic factor (BDNF) is a member of the
      neurotrophic family found in both the central and the peripheral nervous system.
      Blood BDNF levels are considered as a state marker for depression. Methods. We
      investigated serum and plasma levels of BDNF levels in 103 healthy volunteers
      (M/F: 39/64, age: 37+/-12 years) using ELISA methods. Results and Conclusions.
      Serum BDNF levels were 14-fold higher than plasma BDNF levels, and a close
      relationship was found between serum and plasma BDNF levels. 

PMID- 24917324
TI  - Implementing electronic medical records in a psychiatric hospital: A qualitative
      study.
AB  - Abstract The objective of this study is to examine health care professionals'
      opinions of the critical events (opportunities and barriers) surrounding EMR
      implementation in a French teaching psychiatric hospital. This qualitative study
      was based on semi-structured interviews with 115 health care professionals: 16
      psychiatrists, 84 nurses, six psychologists or social assistants and nine
      secretaries or administrative professionals. Interviews were thematically
      analysed. Most responders (96%) used EMR. Among these EMR users, 70% perceived
      EMR positively. Concerning the opportunities from implementing an EMR, the most
      represented theme was "the improved access to medical record information" (75%),
      followed by "the strategy to guarantee the adhesion of professionals and the use
      of EMR" (69%), and "the technological performances of EMR" (49%). Concerning the
      barriers to implementation, four themes emerged, as follows: "the workflow and
      efficiency decrease" (73%), "the triangulation of the patient-professional
      relationship" (47%), "the information sharing and confidentiality" (32%), and
      "the ambiguity of EMR" (26%), which answers both to the production of care and to
      an economic issue. In conclusion, EMR implementation involved several critical
      components, and the strategy of implementation is particularly important.
      Implementing an EMR should be considered a continuous process, and the principle
      and theory of continuous quality improvement appears pertinent for addressing
      this problem. 

PMID- 24917325
TI  - No influence of SLC6A3 40 base VNTR polymorphism on the response to risperidone.
AB  - Abstract Objectives. The SLC6A3 40 base variable number of tandem repeats (VNTR)
      polymorphism has been associated with several clinical phenotypes associated with
      dysregulation of dopamine transmission. However, there is only little evidence
      about a possible influence of such genetic variant on the response to
      antipsychotics. The aim of the present study is to investigate whether SLC6A3 40
      base VNTR polymorphism could modulate response to risperidone in a sample of
      Korean schizophrenia subjects. Methods. One hundred and forty-two schizophrenia
      inpatients were treated with a flexible dose of risperidone. Efficacy was
      assessed at baseline and at discharge using the scores of the Clinical Global
      Impression-severity (CGI-S), Brief Psychiatric Rating Scale (BPRS) and Positive
      and Negative Symptom Score (PANSS). Multivariate analysis of covariance was used
      to test possible influences of SLC6A3 VNTR variants on clinical scores. Results.
      None of the genotypes and of the alleles under investigation was associated with
      clinical scores at discharge or with changes of clinical scores over time. In
      addition, we also failed to find any association between genotypes and allele
      frequency distribution in accordance with treatment response defined as a 20% (or
      30%) or more reduction in the total PANSS scores from the baseline to the end of
      treatment. Conclusion. Our findings do not suggest a possible association between
      SLC6A3 40 base VNTR polymorphism and response to risperidone. However, because of
      several limitations including the investigation of a single drug, the flexible
      design of the present study and the absence of a complete coverage of features
      which could influence the response, further investigations could be required. 

PMID- 24917326
TI  - [Not Available].

PMID- 24917327
TI  - The use of hybrid virus-like particles to enhance the immunogenicity of a broadly
      protective HPV vaccine.
AB  - Virus-like particles (VLPs) can serve as a highly immunogenic vaccine platform
      for the multivalent display of epitopes from pathogens. We have used
      bacteriophage VLPs to develop vaccines that target a highly conserved epitope
      from the human papillomavirus (HPV) minor capsid protein, L2.VLPs displaying an
      L2-peptide from HPV16 elicit antibodies that broadly neutralize infection by HPV
      types associated with the development of cervical cancer. To broaden the cross
      neutralization further, we have developed a strategy to display two different
      peptides on a single, hybrid VLP in a multivalent, highly immunogenic fashion. In
      general, hybrid VLPs elicited high-titer antibody responses against both targets,
      although in one case we observed an immunodominant response against only one of
      the displayed epitopes. Immunization with hybrid particles elicited antibodies
      that were able to neutralize heterologous HPV types at higher titers than those
      elicited by particles displaying one epitope alone, indicating that the hybrid
      VLP approach may be an effective technique to target epitopes that undergo
      antigenic variation.

PMID- 24917328
TI  - Safety as experienced by patients themselves: a Finnish survey of the most recent
      period of care.
AB  - We examined patients' experiences of patient safety and participation in
      promoting safe care during their most recent care period. A survey of patients (N
      = 175) revealed that treatment, medication, and device safety were mostly
      experienced as very good or excellent, but responses varied by age and
      experience. Patients ages 66-75 were most critical of treatment and medication
      safety. Device safety was rated the worst aspect of safety. Twenty percent of
      respondents had experienced errors at some time during their care. Patients who
      had experienced errors and those who were treated at inpatient wards versus a day
      surgery unit were most critical towards patient participation. Open and
      transparent error management involving patients is needed to promote treatment,
      medication, and especially device safety.

PMID- 24917329
TI  - Manipulation of visual biofeedback during gait with a time delayed adaptive
      Virtual Mirror Box.
AB  - BACKGROUND: A mirror placed in the mid-sagittal plane of the body has been used
      to reduce phantom limb pain and improve movement function in medical conditions
      characterised by asymmetrical movement control. The mirrored illusion of
      unimpaired limb movement during gait might enhance the effect, but a physical
      mirror is only capable of showing parallel movement of limbs in real time
      typically while sitting. We aimed to overcome the limitations of physical mirrors
      by developing and evaluating a Virtual Mirror Box which delays the mirrored image
      of limbs during gait to ensure temporal congruency with the impaired physical
      limb. METHODS: An application was developed in the CAREN system's D-Flow software
      which mirrors selected limbs recorded by real-time motion capture to the
      contralateral side. To achieve phase shifted movement of limbs during gait, the
      mirrored virtual limbs are also delayed by a continuously calculated amount
      derived from past gait events. In order to accommodate non-normal proportions and
      offsets of pathological gait, the movements are morphed so that the physical and
      virtual contact events match on the mirrored side. Our method was tested with a
      trans-femoral amputee walking on a treadmill using his artificial limb. Joint
      angles of the elbow and knee were compared between the intact and mirrored side
      using cross correlation, root mean squared difference and correlation
      coefficients. RESULTS: The time delayed adaptive virtual mirror box produced a
      symmetrical looking gait of the avatar coupled with a reduction of the difference
      between the intact and virtual knee and elbow angles (10.86 degrees  and 5.34
      degrees  reduced to 4.99 degrees  and 2.54 degrees  respectively). Dynamic
      morphing of the delay caused a non-significant change of toe-off events when
      compared to delaying by 50% of the previous gait cycle, as opposed to the initial
      contact events which showed a practically negligible but statistically
      significant increase (p < 0.05). CONCLUSIONS: Adding an adaptive time delay to
      the Virtual Mirror Box has extended its use to treadmill gait, for the first
      time. Dynamic morphing resulted in a compromise between mirrored movement of the
      intact side and gait events of the virtual limbs matched with physical events of
      the impaired side. Asymmetrical but repeatable gait is expected to provide even
      more faithful mirroring.

PMID- 24917330
TI  - Application of iPS cells in dental bioengineering and beyond.
AB  - The stem-cell-based tissue-engineering approaches are widely applied in
      establishing functional organs and tissues for regenerative medicine. Successful
      generation of induced pluripotent stem cells (iPS cells) and rapid progress of
      related technical platform provide great promise in the development of
      regenerative medicine, including organ regeneration. We have previously reported
      that iPS cells could be an appealing stem cells source contributing to tooth
      regeneration. In the present paper, we mainly review the application of iPS
      technology in dental bioengineering and discuss the challenges for iPS cells in
      the whole tooth regeneration. 

PMID- 24917331
TI  - Utility values for specific hepatic encephalopathy health states elicited from
      the general public in the United Kingdom.
AB  - BACKGROUND AND AIMS: To elicit utility values for five health states
      corresponding to increasing severity of hepatic encephalopathy, from members of
      the general public in the UK. The health states studied were Conn grades 0, 1, 2,
      3 and 4. METHODS: Interviewer-administered time trade-off (TTO) and standard
      gamble (SG) utilities were elicited for the five health states from a random
      sample of 200 members of the general public in the UK, using health state
      descriptions validated by clinicians and members of the general public. RESULTS:
      Respondents' mean age was 49.5 years and 49% were female. Mean utilities were
      0.962 (TTO) and 0.915 (SG) for Conn grade 0; 0.912 (TTO) and 0.837 (SG) for Conn
      grade 1; 0.828 (TTO) and 0.683 (SG) for Conn grade 2; 0.691 (TTO) and 0.489 (SG)
      for Conn grade 3; and 0.429 (TTO) and 0.215 (SG) for Conn grade 4. The TTO and SG
      values between the five Conn grades were significantly different (p < 0.001).
      Additionally, the TTO value was significantly higher than the SG value for the
      corresponding state (p <0.0001). CONCLUSION: These findings quantify how
      different Conn grades and level of response to treatment may impact on the health
      related quality of life of patients with hepatic encephalopathy. There were
      greater preference values for lower levels of disease, with the highest value
      associated with Conn grade 0. These health state preference values can be used to
      estimate the outcomes of different interventions for hepatic encephalopathy in
      terms of quality-adjusted life years.

PMID- 24917332
TI  - Cognitive aids: time for a change?

PMID- 24917333
TI  - The effects of a displayed cognitive aid on non-technical skills in a simulated
      'can't intubate, can't oxygenate' crisis.
AB  - Guidelines outlining recommended actions are difficult to implement in the
      stressful, time-pressured situation of an airway emergency. Cognitive aids such
      as posters and algorithms improve performance during some anaesthetic
      emergencies; however, their effects on team behaviours have not been determined.
      In this study, 64 participants were randomly assigned into control (no cognitive
      aid) and intervention (cognitive aid provided) groups before a simulated 'can't
      intubate, can't oxygenate' scenario. Video analysis was undertaken of the non
      technical skills and technical performance during the scenarios. All categories
      had higher Anaesthetists' Non-Technical Skills (ANTS) scores when a cognitive aid
      was supplied (mean (SD) total ANTS score 10.4 (3.1) vs. 13.2 (2.4), p < 0.001).
      The number of times the cognitive aid was used was associated with higher ANTS
      scores (rho = 0.383, p = 0.002). A trend towards the establishment of an
      infraglottic airway within 3 min was also noted (control group 55.3% vs.
      intervention 76.9%, p = 0.076). Non-technical skills are improved when a
      cognitive aid is present during airway emergencies.

PMID- 24917334
TI  - Accidental dural puncture: patch or wait?

PMID- 24917335
TI  - Timing of post-dural puncture headache symptoms.

PMID- 24917336
TI  - Aseptic precautions for epidural blood patch.

PMID- 24917337
TI  - A reply.

PMID- 24917338
TI  - Evidence-based fluid optimisation?

PMID- 24917339
TI  - Fluid responsiveness in healthy volunteers: data precision and significance.

PMID- 24917340
TI  - A reply.

PMID- 24917341
TI  - Ventilator malfunction due to Luer lock misconnection.

PMID- 24917342
TI  - Wrongly connected cylinder oxygen supply.

PMID- 24917343
TI  - Cold--or hot? The risk of fire in the operating department.

PMID- 24917344
TI  - Extended roles for videolayngoscopy.

PMID- 24917345
TI  - Teaching fibreoptic bronchoscopy using smart phones.

PMID- 24917346
TI  - Efficacy of one-handed ventilation techniques.

PMID- 24917347
TI  - Scavenging volatiles is not enough to prevent pollution.

PMID- 24917348
TI  - Training anaesthetists about quality improvement.

PMID- 24917349
TI  - Use of intramuscular morphine in trauma patients.

PMID- 24917350
TI  - Diclofenac sodium in Hartmanns solution.

PMID- 24917352
TI  - Sudden asystole during radiofrequency ablation: a case report and literature
      review.
AB  - BACKGROUND: Radiofrequency (RF) ablation is a widely accepted and ideal
      therapeutic tool to cure some tachycardias. The occurrence of complications
      varies depending on the procedure being performed. Sudden unexpected prolonged
      asystole is rare for most ablation procedures and the underlying mechanisms
      remain unclear. CASE PRESENTATION: A case of sudden prolonged asystole induced by
      RF ablation of a concealed left free wall accessory in a 59-year-old woman with
      recurrent tachycardia. RF application provoked progressive slowing of the sinus
      rhythm and then a 13.2-second period of asystole ensued. Asystole was self
      healing and no complications were seen in the following follow-up. CONCLUSIONS:
      RF ablation may develop prolonged asystole due to vagus response caused by
      stimulation of unmyelinated vagal C-fibers or ganglionated plexus (GP).
      Reflexible asystole is reproducible and resolves independently, without affecting
      the procedure of RF ablation.

PMID- 24917351
TI  - Neuroendocrine tumors of extrahepatic biliary tract.
AB  - Neuroendocrine tumors of the extrahepatic bile ducts (EBNETs) are very rare. The
      aim of the present review is to elucidate the characteristics of EBNETs, their
      treatment and prognosis. An exhaustive systematic review of the literature was
      performed from 1959 up-to-date. One hundred articles, describing 150 cases were
      collected. Each article was carefully analyzed and a database was created. The
      most common symptoms were jaundice (60.3 %) and pruritus (19.2 %). Cholelithiasis
      co-existed in 15 cases (19.2 %). Hormone- and vasoactive peptide- related
      symptoms were present in only 7 cases (9 %). The most frequent sites were found
      to be the common hepatic duct and the proximal common bile duct (19.2 %).
      Surgical management was considered the main treatment for EBNETs, while excision
      of extrahepatic biliary tree (62.82 %) with portal vein lymphadenectomy (43.6 %)
      was the most popular procedure. EBNETs are extremely rare. Their rarity makes
      their characterization particularly difficult. Up to date the final diagnosis is
      made after surgery by pathology and immunohistochemistry findings. The present
      analysis of the existing published cases elucidates many aspects of these
      tumours, giving complete clinicopathological documentation.

PMID- 24917353
TI  - Revisualising 'porn': how young adults' consumption of sexually explicit Internet
      movies can inform approaches to Canadian sexual health promotion.
AB  - The Internet offers an invaluable opportunity to re-imagine ideas, constructs and
      disciplines to create innovative sexual health promotion interventions. To gain
      insight into what young adults (aged 19-28) may be seeking in online sexual
      resources and approaches, this study explored how young people perceived their
      sexual health to be influenced by their consumption of the highly utilised sexual
      medium of Sexually Explicit Internet Movies [SEIM]. Employing an exploratory,
      qualitative methodology, data were collected through semi-structured interviews
      with 12 urban, heterosexual young adults, who self-identified as having consumed
      SEIM for a period of at least one year. All interviews were audiotaped with
      permission, transcribed verbatim and the data were analysed to identify emergent
      thematic concepts. Participants described utilising SEIM as an all-inclusive
      sexual forum to learn more about the positive aspects of sexual health, in a
      context that they viewed as being devoid of alternatives. Young adults'
      perceptions of the utility of SEIM suggest that it would be beneficial to create
      novel, sex-positive online sexual health interventions. Further exploration is
      clearly warranted on how Internet resources that are related to sexual health,
      such as SEIM, can be utilised to facilitate innovative approaches to online
      sexual health promotion. 

PMID- 24917354
TI  - Low-volume, high-intensity, aerobic interval exercise for sedentary adults:
      VO2max, cardiac mass, and heart rate recovery.
AB  - PURPOSE: The aim of this study was to compare the effects of low-volume, high
      intensity aerobic interval training (HAIT) on maximal oxygen consumption
      (VO2max), left ventricular (LV) mass, and heart rate recovery (HRR) with high
      volume, moderate-intensity continuous aerobic training (CAT) in sedentary adults.
      METHODS: Twenty-four healthy but sedentary male adults (aged 29.2 +/- 7.2 years)
      participated in an 8-week, 3-day a week, supervised exercise intervention. They
      were randomly assigned to either HAIT (18 min, 180 kcal per exercise session) or
      CAT (45 min, 360 kcal). VO2max, LV mass (3T-MRI), and HRR at 1 min (HRR-1) and 2
      min (HRR-2) after maximal exercise were measured pre- and post-intervention.
      RESULTS: Changes in VO2max during the 8-week intervention were significant (P <
      0.01) in both groups (HAIT, 8.7 +/- 3.2 ml kg(-1) min(-1), 22.4 +/- 8.9%; CAT,
      5.5 +/- 2.8 ml kg(-1) min(-1), 14.7 +/- 9.5%), while the VO2max improvement in
      HAIT was greater (P = 0.02) than in CAT. LV mass in HAIT increased (5.1 +/- 8.4
      g, 5.7 +/- 9.1%, P = 0.05), but not in CAT (0.9 +/- 7.8 g, 1.1 +/- 8.4%, P =
      0.71). While changes in HRR-1 were not significant in either group, change in HRR
      2 for HAIT (9.5 +/- 6.4 bpm, 19.0 +/- 16.0%, P < 0.01) was greater (P = 0.03)
      than for CAT (1.6 +/- 10.9 bpm, 3.9 +/- 16.2%, P = 0.42). CONCLUSIONS: This study
      suggests that HAIT has potential as a time-efficient training mode to improve
      cardiorespiratory capacity and autonomic nervous system function in sedentary
      adults.

PMID- 24917355
TI  - Comparison of the power spectral changes of the voluntary surface electromyogram
      and M wave during intermittent maximal voluntary contractions.
AB  - INTRODUCTION: To compare the power spectral changes of the voluntary surface
      electromyogram (sEMG) and of the compound action potential (M wave) in the vastus
      medialis and vastus lateralis muscles during fatiguing contractions. METHODS:
      Interference sEMG and force were recorded during 48 intermittent 3-s isometric
      maximal voluntary contractions (MVC) from 13 young, healthy subjects. M waves and
      twitches were evoked using supramaximal femoral nerve stimulation between the
      successive MVCs. Mean frequency (F mean), and median frequency were calculated
      from the sEMG and M waves. Muscle fiber conduction velocity (MFCV) was computed
      by cross-correlation. RESULTS: The power spectral shift to lower frequencies was
      significantly greater for the voluntary sEMG than for the M waves (P < 0.05).
      Over the fatiguing protocol, the overall average decrease in MFCV (~25%) was
      comparable to that of sEMG F mean (~22%), but significantly greater than that of
      M-wave F mean (~9%) (P < 0.001). The mean decline in MFCV was highly correlated
      with the mean decreases in both sEMG and M-wave F mean. CONCLUSIONS: The present
      findings indicated that, as fatigue progressed, central mechanisms could enhance
      the relative weight of the low-frequency components of the voluntary sEMG power
      spectrum, and/or the end-of-fiber (non-propagating) components could reduce the
      sensitivity of the M-wave spectrum to changes in conduction velocity.

PMID- 24917356
TI  - High intensity cycling before SCUBA diving reduces post-decompression
      microparticle production and neutrophil activation.
AB  - BACKGROUND: Venous gas emboli (VGE) have traditionally served as a marker for
      decompression stress after SCUBA diving and a reduction in bubble loads is a
      target for precondition procedures. However, VGE can be observed in large
      quantities with no negative clinical consequences. The effect of exercise before
      diving on VGE has been evaluated with mixed results. Microparticle (MP) counts
      and sub-type expression serve as indicators of vascular inflammation and DCS in
      mice. The goal of the present study is to evaluate the effect of anaerobic
      cycling (AC) on VGE and MP following SCUBA diving. METHODS: Ten male divers
      performed two dives to 18 m for 41 min, one dive (AC) was preceded by a repeated
      Wingate cycling protocol; a control dive (CON) was completed without exercise.
      VGE were analyzed at 15, 40, 80, and 120 min post-diving. Blood for MP analysis
      was collected before exercise (AC only), before diving, 15 and 120 min after
      surfacing. RESULTS: VGE were significantly lower 15 min post-diving in the AC
      group, with no difference in the remaining measurements. MPs were elevated by
      exercise and diving, however, post-diving elevations were attenuated in the AC
      dive. Some markers of neutrophil elevation (CD18, CD41) were increased in the CON
      compared to the AC dive. CONCLUSIONS: The repeated-Wingate protocol resulted in
      an attenuation of MP counts and sub-types that have been related to vascular
      injury and DCS-like symptoms in mice. Further studies are needed to determine if
      MPs represent a risk factor or marker for DCS in humans.

PMID- 24917357
TI  - The effects of poling on physiological, kinematic and kinetic responses in roller
      ski skating.
AB  - PURPOSE: We investigated the effects of poling on physiological, kinematic and
      kinetic responses in the G4 skating technique where the poling movement is
      synchronized with the leg push-off on one side (strong side) followed by a
      forward arm swing during the leg push-off on the other side (weak side). METHODS:
      G4 skating with (G4-P) and without (G4-NP) poling was compared in 17 elite male
      cross-country skiers during 4-min submaximal tests on a 2% inclined roller ski
      treadmill at 10, 15 and 20 km h(-1). RESULTS: G4-P demonstrated less ventilatory
      stress and higher gross efficiency compared to G4-NP at all velocities, and the
      blood lactate concentration was lower at the high velocity (all P < 0.05).
      Furthermore, longer cycle lengths and lower cycle rates were found with G4-P at
      all velocities, with correspondingly lower peak ski forces, increased ski
      velocities and less angling and edging of the skis (all P < 0.05). The peak ski
      forces on the strong side were lower than on the weak side with G4-P at all
      velocities (all P < 0.05), but no differences between the sides were found with
      G4-NP. CONCLUSIONS: The reduced physiological cost, higher gross efficiency and
      longer cycle lengths together with the lower ski forces at a given work rate with
      G4-P demonstrate the effectiveness of poling in the G4 skating technique. Thus,
      poling provides possibilities to increase total propulsion, to reduce ski forces
      and to enhance skiing efficiency.

PMID- 24917358
TI  - Basal Ca(2+) signaling is particularly increased in mutated chronic lymphocytic
      leukemia.
AB  - On the basis of somatic hypermutation status of their B-cell antigen receptor
      (BCR) genes, chronic lymphocytic leukemia (CLL) patients can be divided into
      unmutated CLL (U-CLL) or mutated CLL (M-CLL). Approximately 30% of CLL patients
      express a stereotypic BCR, which may indicate that specific antigenic stimulation
      is driving CLL pathogenesis. Recently, it was reported that BCRs from CLL cells
      are capable of antigen-independent, cell-autonomous signaling, through
      recognition of an internal framework 2 (FR2) BCR epitope. We hypothesized that
      the level of cell-autonomous signaling may differ between CLL subgroups.
      Therefore, we analyzed Ca(2+) signaling in a series of primary stereotypic or
      heterogeneous U-CLL and M-CLL (n=68) and healthy controls (n=14). We confirmed
      that basal Ca(2+) signaling in CLL cells is higher than in normal B cells.
      Interestingly, we found that basal signaling was particularly increased in M-CLL.
      The degree of basal signaling did not correlate with membrane immunoglobulin
      levels, HCDR3 characteristics or FR2/FR3 sequence. We conclude that the level of
      basal Ca(2+) signaling is not uniformly enhanced in CLL B cells, but is
      associated with CLL immunoglobulin heavy chain V mutational status, reflecting a
      distinct cellular origin and possibly a different anergic state induced by
      repetitive or continuous antigen binding in vivo. 

PMID- 24917359
TI  - Activating human genes with zinc finger proteins, transcription activator-like
      effectors and CRISPR/Cas9 for gene therapy and regenerative medicine.
AB  - New technologies have recently been developed to control the expression of human
      genes in their native genomic context by engineering synthetic transcription
      factors that can be targeted to any DNA sequence. The ability to precisely
      regulate any gene as it occurs naturally in the genome provides a means to
      address a variety of diseases and disorders. This approach also circumvents some
      of the traditional challenges of gene therapy. In this editorial, we review the
      technologies that have enabled targeted human gene activation, including the
      engineering of transcription factors based on zinc finger proteins, transcription
      activator-like effectors and the CRISPR/Cas9 system. Additionally, we highlight
      examples in which these methods have been developed for therapeutic applications
      and discuss challenges and opportunities. 

PMID- 24917360
TI  - Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective
      cohort of never smoking women in Shanghai, China.
AB  - Indoor air pollution (IAP) caused by cooking has been associated with lung cancer
      risk in retrospective case-control studies in developing and rural countries. We
      report the association of cooking conditions, fuel use, oil use, and risk of lung
      cancer in a developed urban population in a prospective cohort of women in
      Shanghai. A total of 71,320 never smoking women were followed from 1996 through
      2009 and 429 incident lung cancer cases were identified. Questionnaires collected
      information on household living and cooking practices for the three most recent
      residences and utilization of cooking fuel and oil, and ventilation conditions.
      Cox proportional hazards regression estimated the association for kitchen
      ventilation conditions, cooking fuels, and use of cooking oils for the risk of
      lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever
      poor kitchen ventilation was associated with a 49% increase in lung cancer risk
      (HR: 1.49; 95% CI: 1.15-1.95) compared to never poor ventilation. Ever use of
      coal was not significantly associated. However, ever coal use with poor
      ventilation (HR: 1.69; 95% CI: 1.22-2.35) and 20 or more years of using coal with
      poor ventilation (HR: 2.03; 95% CI: 1.35-3.05) was significantly associated
      compared to no exposure to coal or poor ventilation. Cooking oil use was not
      significantly associated. These results demonstrate that IAP from poor
      ventilation of coal combustion increases the risk of lung cancer and is an
      important public health issue in cities across China where people may have lived
      in homes with inadequate kitchen ventilation. 

PMID- 24917362
TI  - Selective extraction of catecholamines by packed fiber solid-phase using
      composite nanofibers composing of polymeric crown ether with polystyrene.
AB  - For the first time, electrospun composite nanofibers comprising polymeric crown
      ether with polystyrene (PCE-PS) have been used for the selective extraction of
      catecholamines - dopamine (DA), norepinephrine (NE) and epinephrine (E) - prior
      to their analysis by high-performance liquid chromatography-electrochemical
      detection. Using a minicartridge packed with PCE-PS composite nanofibers, the
      target compounds were extracted effectively from urine samples to which
      diphenylborinic acid 2-aminoethyl ester was added as a complexing reagent. The
      extracted catecholamines could be liberated from the fiber by the addition of
      acetic acid. A good linearity was observed for catecholamines in the range of 2.0
      200 ng mL(-1) (NE, E and DA). The detection limits of catecholamines (signal-to
      noise ratio = 3) were 0.5 ng mL(-1) (NE), 0.2 ng mL(-1) (E) and 0.2 ng mL(-1)
      (DA), respectively. Under the optimized conditions, the absolute recoveries of
      the above three catecholamines were 90.6% (NE), 88.5% (E) and 94.5% (DA). The
      repeatability of extraction performance was from 5.4 to 9.2% (expressed as
      relative standard deviation). Our results indicate that the proposed method could
      be used for the determination of NE, E and DA in urine.

PMID- 24917361
TI  - Low expression of secreted frizzled-related protein 4 in aggressive pituitary
      adenoma.
AB  - OBJECTIVE: The secreted frizzled-related proteins (sFRPs) are reported to be
      antagonists of a number of tumors. This study was designed to investigate the
      relationship of sFRP4 with aggressiveness of pituitary adenomas. MATERIAL AND
      METHOD: Specimens were classified into three groups: normal control (n = 10), non
      aggressive group (n = 42) and aggressive group (n = 26) according to preoperative
      magnetic resonance imaging (MRI)/computed tomography. sFRP4 were investigated by
      PCR, Western blotting, and immunohistochemistry (IHC). The methylation status of
      the sFRP4 promoter region was observed by MassArray. Cell culture and 5-aza-2
      deoxycytidine treatment was performed to observe the relationship of
      downregulation of sFRP4 with methylation of the sFRP4 gene. RESULTS: PCR and
      Western blot results showed that sFRP4 expression was downregulated in aggressive
      pituitary adenomas, which was confirmed by IHC. Methylation of the sFRP4 promoter
      was increased in aggressive pituitary adenomas. And methylation of the sFRP4
      promoter lead to downregulation of sFRP4 expression. CONCLUSIONS: sFRP4
      expression is inversely related to the aggressiveness of pituitary adenomas, and
      act as a tumor suppressor.

PMID- 24917363
TI  - Direct and indirect hydrogen abstraction in Cl + alkene reactions.
AB  - Reactions between Cl atoms and propene can lead to HCl formation either by direct
      H abstraction or through a chloropropyl addition complex. Barring stabilizing
      collisions, the chloropropyl radical will either decompose to reactants or form
      HCl and allyl products. Using velocity-map imaging to measure the quantum state
      and velocity of the HCl products provides a view into the reaction dynamics,
      which show signs of both direct and indirect reaction mechanisms. Simulated
      trajectories of the reaction highlight the role of the direct H-abstraction
      pathways, and the resultant simulated scattering images show reasonable agreement
      with measurement. The simulations also show the importance of large excursions of
      the Cl atom far from equilibrium geometries within the chloropropyl complex, and
      these large-amplitude motions are the ultimate drivers toward HCl + allyl
      fragmentation. Gas-phase measurements of larger alkenes, 2-methylpropene and 2,3
      dimethylbut-2-ene, show slightly different product distributions but still
      feature similar reaction dynamics. The current suite of experiments offers ready
      extensions to liquid-phase bimolecular reactions. 

PMID- 24917364
TI  - Age-related changes in the distribution of transient receptor potential vanilloid
      4 channel (TRPV4) in the central nervous system of rats.
AB  - Transient receptor potential vanilloid type 4 (TRPV4) channels are expressed in
      the central nervous system, but their role in regulating the aging process under
      physiological and pathological conditions is still largely unknown. To identify
      age-related changes in the TRPV4 channel that contribute to the central nervous
      system, we investigated the distribution of TRPV4 in the brain and spinal cord
      regions of adult and aged rats. The expression of TRPV4 in the brain and spinal
      cord of adult and aged Sprague-Dawley rats was compared using
      immunohistochemistry performed with antibodies recognizing TRPV4 on free floating
      sections and western blotting analysis. TRPV4 immunoreactivity was significantly
      increased in the cerebral cortex, hippocampal formation, thalamus, basal nuclei,
      cerebellum and spinal cord of aged rats compared with adult control rats. In the
      cerebral cortex, TRPV4 immunoreactivity was significantly increased in pyramidal
      cells of aged rats. In addition, TRPV4 immunoreactivity was increased in the
      spinal cord, hippocampal formation, thalamus, basal nuclei and cerebellum of aged
      rats. This first demonstration of age-related increases in TRPV4 expression in
      the brain and spinal cord may provide useful data for investigating the
      pathogenesis of age-related neurodegenerative diseases. The exact regulatory
      mechanism and its functional significance require further elucidation. 

PMID- 24917365
TI  - Associations between polymorphisms of HLA-B gene and postmenopausal osteoporosis
      in Chinese Han population.
AB  - Osteoporosis is a systemic skeletal disease, which is more prevalent in
      postmenopausal women. Osteoporosis likely develops beginning with genetic risk.
      This study explored the relationships between polymorphisms of HLA-B gene and
      postmenopausal osteoporosis in a Chinese Han population. Polymerase chain
      reaction sequence-based typing (PCR-SBT) method was used for DNA typing at HLA-B
      locus in 70 patients with postmenopausal osteoporosis and 73 healthy controls in
      female Han population of Shaanxi Province, situated in north-western China. We
      found that 40 HLA-B alleles in postmenopausal osteoporosis patients and control
      subjects, respectively. Furthermore, the frequency of HLA-B* 3501 allele was
      significantly higher in postmenopausal osteoporosis patients than in the control
      group (P = 0.033), and the relative risk was 7.632 (95% CI: 0.927-62.850). Our
      results suggest that HLA-B* 3501 was likely an important risk factor for
      postmenopausal osteoporosis. As different populations have different HLA
      polymorphisms, further investigation of the relationship of various HLA genes and
      osteoporosis with larger sample size is still necessary in the future.

PMID- 24917366
TI  - Description of Brenneria roseae sp. nov. and two subspecies, Brenneria roseae
      subspecies roseae ssp. nov and Brenneria roseae subspecies americana ssp. nov.
      isolated from symptomatic oak.
AB  - Gram-negative, facultatively anaerobic bacteria were isolated from symptomatic
      oak tissue in the UK and USA. Partial gyrB sequencing placed ten strains in the
      genus Brenneria, with B. goodwinii as the closest phylogenetic relative. The
      strains were investigated further using a polyphasic approach including MLSA
      (based on partial gyrB, rpoB, infB and atpD gene sequences), 16S rRNA gene
      sequencing, DNA-DNA relatedness studies and both phenotypic and chemotaxonomic
      assays. The MLSA and 16S rRNA gene analyses separated the strains into two groups
      based on origin, suggesting that they belong to Brenneria as two novel species.
      However, the DNA-DNA relatedness values revealed a closer relationship between
      the groups and indicated that they should belong to the same species. As the two
      groups of strains from the UK and USA can be differentiated from each other
      phenotypically and by ERIC PCR fingerprints, it is proposed to classify them as
      novel subspecies of a novel Brenneria species. The name Brenneria roseae sp. nov.
      (FRB 222(T)=LMG 27714(T)=NCPPB 4581(T)) is proposed, with Brenneria roseae subsp.
      roseae ssp. nov. (FRB 222(T)=LMG 27714(T)=NCPPB 4581(T)) for the strains from the
      UK and Brenneria roseae subsp. americana ssp. nov. (FRB 223(T)=LMG 27715(T)=NCPPB
      4582(T)) for the strains from the USA.

PMID- 24917367
TI  - Co-treatment of fruit and vegetable waste in sludge digesters. An analysis of the
      relationship among bio-methane generation, process stability and digestate
      phytotoxicity.
AB  - The co-digestion of a variable amount of fruit and vegetable waste in a waste
      mixed sludge digester was investigated using a pilot scale apparatus. The organic
      loading rate (OLR) was increased from 1.46 kg VS/m(3) day to 2.8 kg VS/m(3) day.
      The hydraulic retention time was reduced from 14 days to about 10 days. Specific
      bio-methane production increased from about 90 NL/kg VS to the maximum value of
      about 430 NL/kg VS when OLR was increased from 1.46 kg VS/m(3) day to 2.1 kg
      VS/m(3) day. A higher OLR caused an excessive reduction in the hydraulic
      retention time, enhancing microorganism wash out. Process stability evaluated by
      the total volatile fatty acids concentration (mg/l) to the alkalinity buffer
      capacity (eq. mg/l CaCO3) ratio (i.e. FOS/TAC) criterion was <0.1 indicating high
      stability for OLR <2.46 kg VS/m(3 )day. For higher OLR, FOS/TAC increased
      rapidly. Residual phytotoxicty of the digestate evaluated by the germination
      index (GI) (%) was quite constant for OLR<2.46 kg VS/m(3)day, which is lower than
      the 60% limit, indicating an acceptable toxicity level for crops. For OLR>2.46 kg
      VS/m(3) day, GI decreased rapidly. This corresponding trend between FOS/TAC and
      GI was further investigated by the definition of the GI ratio (GIR) parameter.
      Comparison between GIR and FOS/TAC suggests that GI could be a suitable criterion
      for evaluating process stability.

PMID- 24917368
TI  - Longitudinal data analysis in support of functional stability concepts for
      leachate management at closed municipal landfills.
AB  - Landfill functional stability provides a target that supports no environmental
      threat at the relevant point of exposure in the absence of active control
      systems. With respect to leachate management, this study investigates "gateway"
      indicators for functional stability in terms of the predictability of leachate
      characteristics, and thus potential threat to water quality posed by leachate
      emissions. Historical studies conducted on changes in municipal solid waste (MSW)
      leachate concentrations over time (longitudinal analysis) have concentrated on
      indicator compounds, primarily chemical oxygen demand (COD) and biochemical
      oxygen demand (BOD). However, validation of these studies using an expanded
      database and larger constituent sets has not been performed. This study evaluated
      leachate data using a mixed-effects regression model to determine the extent to
      which leachate constituent degradation can be predicted based on waste age or
      operational practices. The final dataset analyzed consisted of a total of 1402
      samples from 101 MSW landfills. Results from the study indicated that all
      leachate constituents exhibit a decreasing trend with time in the post-closure
      period, with 16 of the 25 target analytes and aggregate classes exhibiting a
      statistically significant trend consistent with well-studied indicators such as
      BOD. Decreasing trends in BOD concentration after landfill closure can thus be
      considered representative of trends for many leachate constituents of concern.

PMID- 24917369
TI  - Extracavitary primary effusion lymphoma presenting as a cutaneous tumor: a case
      report and literature review.
AB  - Primary effusion lymphoma is an unusual form of aggressive B-cell lymphoma
      universally associated with human herpesvirus 8 (HHV8) that involves mostly human
      immunodeficiency virus (HIV)-infected patients. Characteristically, it presents
      as a malignant serous effusion involving body cavities, but without associated
      tumor mass. Exceptionally, HHV8-positive lymphomas with features identical to
      primary effusion lymphoma may present as mass lesions in the absence of cavity
      effusions along the course of the disease, and are regarded as extracavitary or
      solid variants of the disorder. These rare forms are extremely rare in the skin.
      We report a case of extracavitary primary effusion lymphoma arising in a HIV
      infected male, who presented with two subcutaneous masses involving the skin of
      the abdominal and inguinal regions as the first manifestation of the process.
      Kaposi sarcoma was not present in the skin surface or mucous membranes. Extensive
      studies failed to demonstrate involvement of other organs and the case was
      considered as an example of extracavitary primary effusion lymphoma originating
      primarily in the skin. Herein, we review the few reported cases of solid primary
      effusion lymphoma involving the skin in order to delineate the clinicopathologic,
      immunohistochemical and molecular characteristics of this rare lymphoma in the
      skin. 

PMID- 24917370
TI  - Stroke self-management: a focus group study to identify the factors influencing
      self-management following stroke.
AB  - BACKGROUND: Self-management refers to the strategies, decisions and activities
      individuals take to manage a long-term health condition. Self-management has
      potential importance for reducing both the personal and health service impact of
      illness. Stroke represents a significant health and social burden, however there
      is a lack of clarity about the factors that support successful self-management
      following stroke. OBJECTIVE: This study sought to investigate the factors which
      facilitate or hinder stroke self-management from the patients' perspective.
      DESIGN: Nested qualitative exploratory phase within a mixed-methods paradigm.
      Data were analysed thematically using Analytic Induction to guide development of
      themes. SETTING: Participants had experienced a stroke and were recruited from
      rural and urban community stroke support groups based in the South of England.
      METHOD: Five focus groups (n=28) using a semi-structured interview guide were
      conducted. Interviews were digitally recorded and transcribed. FINDINGS: The term
      'self-management' was unfamiliar to participants. On further exploration,
      participants described how self-management activities were helped or hindered.
      Self-management was viewed as an important, unavoidable feature of life after
      stroke. Three key themes identified from the data affect stroke self-management:
      Individual capacity; support for self-management and self-management environment.
      People following stroke reported feeling ill-prepared to self-manage. The self
      management support needs of patients following stroke are currently often unmet.
      CONCLUSION: Successful stroke self-management consists of features which may be
      modifiable at the individual level, in addition to the presence of external
      support and an environment which supports and facilitates people following stroke
      to self-manage. These findings extend current conceptualisations of stroke self
      management.

PMID- 24917371
TI  - Complication prevalence following use of tutoplast-derived human acellular dermal
      matrix in prosthetic breast reconstruction: a retrospective review of 203
      patients.
AB  - Use of human acellular dermal matrix (ADM) during prosthetic breast
      reconstruction has increased. Several ADM products are available produced by
      differing manufacturing techniques. It is not known if outcomes vary with
      different products. This study reports the complication prevalence following use
      of a tutoplast-derived ADM (T-ADM) in prosthetic breast reconstruction. We
      performed a retrospective chart review of 203 patients (mean follow-up times 12.2
      months) who underwent mastectomy and immediate prosthetic breast reconstruction
      utilizing T-ADM, recording demographic data, surgical indications and
      complication (infection, seroma, hematoma, wound healing exceeding three weeks
      and reconstruction failure). During a four-year period, 348 breast
      reconstructions were performed Complications occurred in 16.4% of reconstructed
      breasts. Infection occurred in 6.6% of breast reconstructions (3.7% - major
      infection, requiring intravenous antibiotics and 2.9% minor infection, requiring
      oral antibiotics only). Seromas occurred in 3.4% and reconstruction failure
      occurred in 0.6% of breast reconstructions. Analysis suggested that complication
      prevalence was significantly higher in patients with a BMI >30 (p = 0.03). The
      complication profile following T-ADM use is this series is comparable to that
      reported for with other ADM products. T-ADM appears to be a safe and acceptable
      option for use in ADM-assisted breast reconstruction. 

PMID- 24917372
TI  - Response to "the ulnar palmar perforator flap: anatomical study and clinical
      application".

PMID- 24917373
TI  - A functional periorbital subunit allograft: vascular, anatomic, and technical
      considerations for future subunit facial transplantation.
AB  - BACKGROUND: Injury to the face can result in the loss of critical specialized
      structures (the eyelids, lips, ears and nose). Vascularized composite
      allotransplantation (VCA) allows the surgeon to replace exactly what has been
      lost. The success of the clinical face transplants suggests the possibility of
      transplanting specialized units of the face. In this study we explore the
      neurovascular anatomy and technical specifics for harvest of a functional
      composite eyelid subunit flap. METHODS: 12 fresh cadaver heads were studied, each
      yielding two flaps (N = 24). The facial (FA) and superficial temporal arteries
      (STA) were cannulated and injected with a gelatin/acrylic dye mixture. 6 cadaver
      heads were evaluated via high-resolution three-dimensional CT scans with
      contrast. RESULTS: The dye injected into the STA uniformly stained the tissue of
      the eyelid/periorbital subunit. Injection into the FA resulted in staining of the
      skin and soft tissues in the medial canthal region and superior eyelid skin in
      66% of specimens. CT scan studies confirm our findings with injection into the
      STA resulting in contrast infiltration of the palpebral arterial arcades in all
      cases. Injection of the FA resulted in contrast infiltration of the palpebral
      arterial arcades in 2 of 3 cases. CONCLUSIONS: Based this study, a periorbital
      flap can be based on the STA. Motor innervation of the flap is via the zygomatic
      and buccal branches of the facial nerve with sensory innervation via the
      infraorbital, supraorbital and supratrochlear nerves. FA could be used, but its
      ability to perfuse the entire flap was inconsistent.

PMID- 24917374
TI  - Does primary closure for dog bite wounds increase the incidence of wound
      infection? A meta-analysis of randomized controlled trials.

PMID- 24917375
TI  - Confirming perforator patency and cross midline arterial arborisation in DIEP
      flap surgery.

PMID- 24917376
TI  - Development of an oral mucosa model to study host-microbiome interactions during
      wound healing.
AB  - Crosstalk between the human host and its microbiota is reported to influence
      various diseases such as mucositis. Fundamental research in this area is however
      complicated by the time frame restrictions during which host-microbe interactions
      can be studied in vitro. The model proposed in this paper, consisting of an oral
      epithelium and biofilm, can be used to study microbe-host crosstalk in vitro in
      non-infectious conditions up to 72 h. Microbiota derived from oral swabs were
      cultured on an agar/mucin layer and challenged with monolayers of keratinocytes
      grown on plastic or collagen type I layers embedded with fibroblasts. The overall
      microbial biofilm composition in terms of diversity remained representative for
      the oral microbiome, whilst the epithelial cell morphology and viability were
      unaffected. Applying the model to investigate wound healing revealed a reduced
      healing of 30 % in the presence of microbiota, which was not caused by a
      reduction of the proliferation index (52.1-61.5) or a significantly increased
      number of apoptotic (1-1.13) or necrotic (32-30.5 %) cells. Since the model
      allows the separate study of the microbial and cellular exometabolome, the
      biofilm and epithelial characteristics after co-culturing, it is applicable for
      investigations within fundamental research and for the discovery and development
      of agents that promote wound healing.

PMID- 24917377
TI  - The first set of expressed sequence tags (EST) from the medicinal mushroom
      Agaricus subrufescens delivers resource for gene discovery and marker
      development.
AB  - Agaricus subrufescens is one of the most important culinary-medicinal cultivable
      mushrooms with potentially high-added-value products and extended agronomical
      valorization. The development of A. subrufescens-related technologies is hampered
      by, among others, the lack of suitable molecular tools. Thus, this mushroom is
      considered as a genomic orphan species with a very limited number of available
      molecular markers or sequences. To fill this gap, this study reports the
      generation and analysis of the first set of expressed sequence tags (EST) for A.
      subrufescens. cDNA fragments obtained from young sporophores (SP) and vegetative
      mycelium in liquid culture (CL) were sequenced using 454 pyrosequencing
      technology. After assembly process, 4,989 and 5,125 sequences were obtained in SP
      and CL libraries, respectively. About 87% of the EST had significant similarity
      with Agaricus bisporus-predicted proteins, and 79% correspond to known proteins.
      Functional categorization according to Gene Ontology could be assigned to 49% of
      the sequences. Some gene families potentially involved in bioactive compound
      biosynthesis could be identified. A total of 232 simple sequence repeats (SSRs)
      were identified, and a set of 40 EST-SSR polymorphic markers were successfully
      developed. This EST dataset provides a new resource for gene discovery and
      molecular marker development. It constitutes a solid basis for further genetic
      and genomic studies in A. subrufescens.

PMID- 24917378
TI  - Synthesis, cytotoxic, and antitumor activities of 2-pyridylhydrazones derived
      from 3-benzoylpyridazines.
AB  - A series of 2-pyridylhydrazones derived from phenyl-pyridazin-3-yl-methanones
      were prepared in search for potential novel antitumor agents. The stereochemistry
      of these compounds was established by means of NMR spectroscopy. Whereas
      hydrazones derived from 3-benzoylpyridazines (IC50  = 0.99-8.74 uM) inhibited the
      proliferation of the tumor cell lines tested, the non-fully aromatic 3
      benzoylpyridazinone hydrazones (IC50  >10 uM) turned out to be inactive.
      Compounds E-1b (IC50  = 0.12 uM) and E-1d (IC50  = 0.18 uM) exert high cytotoxic
      activities in clonogenic assays involving human tumor cells of different tissue
      origins. In vivo application of compound E-1b (300 mg/kg/day) resulted in a 66%
      reduction in tumor burden.

PMID- 24917380
TI  - Experimental and computational studies of the neutral and reduced states of
      indeno[1,2-b]fluorene.
AB  - This study examines the intrinsic structural and optoelectronic properties of the
      neutral indeno[1,2-b]fluorene skeleton as well as those of the corresponding
      anion radical and dianion. We report their characterization by analysis of solid
      state structures and EPR, NMR, and absorbance spectra. Additionally, 20 popular
      density functional theory methods are used to evaluate their performance for
      predicting NMR chemical shifts, EPR hyperfine coupling constants, and low-energy
      transitions of the absorbance spectrum to act as a guide for future studies. This
      information can be used for a better understanding and tuning of the electron
      transporting/accepting ability of the indenofluorene core for use in organic
      photovoltaics and organic field effect transistors. 

PMID- 24917379
TI  - Classification framework for graphene-based materials.
AB  - Graphing graphene: Because the naming of graphene-based materials (GBMs) has led
      to confusion and inconsistency, a classification approach is necessary. Three
      physical-chemical properties of GBMs have been defined by the GRAPHENE Flagship
      Project of the European Union for the unequivocal classification of these
      materials (see grid). 

PMID- 24917381
TI  - Usefulness of contrast-enhanced ultrasonography using Sonazoid for the assessment
      of therapeutic response to percutaneous radiofrequency ablation for
      hepatocellular carcinoma.
AB  - AIM: Accurate assessment of the coagulated area is imperative to achieve an
      excellent outcome from percutaneous radiofrequency ablation (PRFA) for the
      treatment of hepatocellular carcinoma (HCC). We evaluated the efficacy of
      contrast-enhanced ultrasonography (CEUS) with the contrast-enhancing agent
      Sonazoid for precisely assessing the therapeutic effect of PRFA for HCC. METHODS:
      We enrolled 87 consecutive patients with solitary naive HCC of less than 3 cm in
      diameter. PRFA treatment was performed with a 17-G cool-tip needle, and CEUS was
      performed to assess the ablative margin 3 h after the procedure, when the
      coagulated tumor outline was easiest to discern. The treatment was repeated until
      an ablative margin greater than 5 mm was confirmed. After CEUS assessment of the
      therapeutic response, the patients were followed to investigate local tumor
      recurrence. RESULTS: In 78 patients (89.7%), the outline of the coagulated tumors
      could be recognized by ultrasonography, and CEUS assessment of the ablative
      margin was successful. The remaining nine patients were assessed by computed
      tomography. The 5-year cumulative survival rate after the assessment of the
      treatment response with CEUS was 58.4%, and the 4-year cumulative total
      recurrence rate was 72.3%. The 5-year cumulative local tumor recurrence rate was
      very low (2.3%). CONCLUSION: The assessment with CEUS at 3 h after the PRFA
      procedure was successful in the majority of the patients, and it yielded a very
      low rate of local recurrence.

PMID- 24917383
TI  - Within-season variation in sexual selection in a fish with dynamic sex roles.
AB  - The strength of sexual selection may vary between species, among populations and
      within populations over time. While there is growing evidence that sexual
      selection may vary between years, less is known about variation in sexual
      selection within a season. Here, we investigate within-season variation in sexual
      selection in male two-spotted gobies (Gobiusculus flavescens). This marine fish
      experiences a seasonal change in the operational sex ratio from male- to female
      biased, resulting in a dramatic decrease in male mating competition over the
      breeding season. We therefore expected stronger sexual selection on males early
      in the season. We sampled nests and nest-holding males early and late in the
      breeding season and used microsatellite markers to determine male mating and
      reproductive success. We first analysed sexual selection associated with the
      acquisition of nests by comparing nest-holding males to population samples. Among
      nest-holders, we calculated the potential strength of sexual selection and
      selection on phenotypic traits. We found remarkable within-season variation in
      sexual selection. Selection on male body size related to nest acquisition changed
      from positive to negative over the season. The opportunity for sexual selection
      among nest-holders was significantly greater early in the season rather than late
      in the season, partly due to more unmated males. Overall, our study documents a
      within-season change in sexual selection that corresponds with a predictable
      change in the operational sex ratio. We suggest that many species may experience
      within-season changes in sexual selection and that such dynamics are important
      for understanding how sexual selection operates in the wild. 

PMID- 24917384
TI  - Positive regulations of adipogenesis by Italian ryegrass [Lolium multiflorum] in
      3T3-L1 cells.
AB  - BACK GROUND: Intramuscular fat deposition in the meat animal is relatively new
      strategy for developing the meat quality. Fat deposition is largely depending on
      the adipocyte proliferation and differentiation. Therefore, we investigated the
      effect of chloroform extract of L. multiflorum [CELM] on cell proliferation,
      lipid accumulation and adipocyte differentiation in 3T3-L1 cells and body weight
      of mouse. RESULTS: We identified 6,9-Octadecatrienoic acid, Hexadecanoic acid, 2
      hydroxypropanoic acid, butane-2,3-diol and hexane-1,2,3,4,5,6-hexaol in CELM. L.
      multiflorum extract increased the cell viability, lipid accumulation, cell cycle
      progression and key transcriptional and secretory factors like PPRAgamma2, C/CEBP
      alpha, adiponectin, aP2, GLUT-4, FAS and SREBP-1 mRNA expression as compared with
      control cells. For in-vivo, mice administered with CELM significantly increased
      body weight throughout the experiment periods. Further, the identified fatty
      acids like 3, 6, 9-Octadecatrienoic acid and Hexadecanoic acid was docked with
      target protein [PPRAgamma2] using HEX 6.12. The least binding energy considered
      as high affinity with target protein. The maximum affinity with the target
      protein was observed in the Hexadecanoic acid followed by 3, 6, 9
      Octadecatrienoic acid. The binding efficacy of Hexadecanoic acid and 3, 6, 9
      Octadecatrienoic acid to the active site of PPAR-gamma2 may be enhanced the
      adipocyte differentiations. CONCLUSION: These findings suggest that CELM
      stimulates adipogenesis via activating the PPARgamma-mediated signaling pathway
      in adipocyte which could be useful for the development of meat quality in
      animals.

PMID- 24917385
TI  - Eavesdropping on heterospecific alarm calls: from mechanisms to consequences.
AB  - Animals often gather information from other species by eavesdropping on signals
      intended for others. We review the extent, benefits, mechanisms, and ecological
      and evolutionary consequences of eavesdropping on other species' alarm calls.
      Eavesdropping has been shown experimentally in about 70 vertebrate species, and
      can entail closely or distantly related species. The benefits of eavesdropping
      include prompting immediate anti-predator responses, indirect enhancement of
      foraging or changed habitat use, and learning about predators. Eavesdropping on
      heterospecifics can provide more eyes looking for danger, complementary
      information to that from conspecifics, and potentially information at reduced
      cost. The response to heterospecific calls can be unlearned or learned. Unlearned
      responses occur when heterospecific calls have acoustic features similar to that
      used to recognize conspecific calls, or acoustic properties such as harsh sounds
      that prompt attention and may allow recognition or facilitate learning. Learning
      to recognize heterospecific alarm calls is probably essential to allow
      recognition of the diversity of alarm calls, but the evidence is largely
      indirect. The value of eavesdropping on different species is affected by problems
      of signal interception and the relevance of heterospecific alarm calls to the
      listener. These constraints on eavesdropping will affect how information flows
      among species and thus affect community function. Some species are 'keystone'
      information producers, while others largely seek information, and these
      differences probably affect the formation and function of mixed-species groups.
      Eavesdroppers might also integrate alarm calls from multiple species to extract
      relevant and reliable information. Eavesdropping appears to set the stage for the
      evolution of interspecific deception and communication, and potentially affects
      communication within species. Overall, we now know that eavesdropping on
      heterospecific alarm calls is an important source of information for many species
      across the globe, and there are ample opportunities for research on mechanisms,
      fitness consequences and implications for community function and signalling
      evolution. 

PMID- 24917386
TI  - Spinal cord stimulation for electrical storm refractory to conventional medical
      treatment: an emerging indication?
AB  - OBJECTIVE: To observe the effect of thoracic spinal cord stimulation with dual
      octipolar epidural electrodes on episodes of ventricular tachycardia and
      ventricular fibrillation in a patient with nonischemic familial cardiomyopathy
      and severe electrical storm refractory to conventional medical treatment.
      RESULTS: Following implantation of temporary bilateral octipolar thoracic
      epidural electrodes and constant low-grade stimulation, episodes of ventricular
      tachycardia and ventricular fibrillation were eradicated, and a permanent system
      was surgically implanted uneventfully. Electrical storm ceased thereafter, though
      ventricular function from progressive cardiomyopathy worsened, requiring heart
      transplantation several months later. CONCLUSIONS: Spinal cord stimulation may
      play an important therapeutic role in the treatment of refractory electrical
      storm when conventional medical treatments have failed. The mechanism by which
      stimulation of the spinal cord confers a therapeutic effect is not completely
      understood, although direct modulation of sympathetic and parasympathetic tone in
      the cardiac conduction system is most likely, based on animal models of ischemia
      induced ventricular tachycardia.

PMID- 24917387
TI  - Risk of epilepsy among patients with atopic dermatitis: a nationwide longitudinal
      study.
AB  - OBJECTIVE: Both atopic dermatitis and epilepsy have been regarded as chronic
      inflammatory diseases. However, their association has yet to be investigated.
      METHODS: Using the Taiwan National Health Insurance Research Database, 35,312
      patients with atopic dermatitis but without a history of epilepsy, and 35,312 age
      /gender-matched controls were enrolled between 1998 and 2008, and followed to the
      end of 2011 to identify the development of epilepsy. RESULTS: Subjects with
      atopic dermatitis had a higher incidence of developing epilepsy (0.94 vs.
      0.27/1,000 person-years, p < 0.001) than the control group. The Cox regression
      model showed that atopic dermatitis increased the risk of developing epilepsy
      (hazard ratio [HR] 2.91, 95% confidence interval [CI] 2.23-3.82) after adjusting
      for demographic data and medical comorbidities. Sensitivity tests showed
      consistent findings (HR 2.32, 95% CI 1.68-2.96) after excluding the first year of
      observation. In addition, asthma (HR 1.34, 95% CI 1.04-1.72) and allergic
      rhinitis (HR 1.34, 95% CI 1.04-1.73) were related to the risk of epilepsy.
      SIGNIFICANCE: Subjects with atopic dermatitis were associated with an increased
      risk of developing epilepsy in later life. Further studies would be needed to
      investigate the underlying mechanisms.

PMID- 24917388
TI  - Ferruginibacter profundus sp. nov., a novel member of the family
      Chitinophagaceae, isolated from freshwater sediment of a reservoir.
AB  - A Gram-negative, aerobic, non-motile, and rod-shaped bacterium, designated strain
      DS48-5-3(T), was isolated from a 48 m sediment sample taken from Daechung
      Reservoir, Republic of Korea. Comparative 16S rRNA gene sequence studies showed a
      clear affiliation of this strain to the Bacteroidetes, notably most closely
      related to Ferruginibacter alkalilentus HU1-GD23(T), Ferruginibacter lapsinanis
      HU1-HG42(T) and Ferruginibacter yonginensis HME8442(T), showing 16S rRNA gene
      sequence similarities to the type strains of these species of 95.2-96.4 %
      similarity. The predominant ubiquinone was identified as MK-7. The major fatty
      acids were identified as iso-C15:0, iso-C17:0 3-OH, and iso-C15:1 G. The G+C
      content of the genomic DNA of strain DS48-5-3(T) was determined to be 37.2 %. On
      the basis of polyphasic evidence, it is proposed that strain DS48-5-3(T) should
      belong to a novel species, for which the name Ferruginibacter profundus sp. nov.
      (type strain DS48-5-3(T) = KCTC 32478(T) = JCM 19431(T)), is proposed. 

PMID- 24917389
TI  - Oncologic, functional and surgical outcomes of primary Transoral Robotic Surgery
      for early squamous cell cancer of the oropharynx: a systematic review.
AB  - OBJECTIVES: Transoral Robotic Surgery (TORS) has emerged as an alternative to
      radiotherapy or chemoradiotherapy for the treatment of oropharyngeal squamous
      cell carcinoma (OPSCC). Many centers restrict the use of TORS to early (T1-2)
      OPSCC. The purpose of this article was to assess oncologic and functional
      outcomes of TORS for primary treatment of early OPSCC. STUDY DESIGN: Systematic
      review. METHODS: A systematic literature search was performed for all relevant
      English language studies using Embase, Medline, and Pubmed. Our primary outcome
      measure was local control; secondary outcomes included overall survival (OS) and
      tracheostomy tube (TT) and gastrostomy tube (GT) dependence rates. Three authors
      independently extracted study information and analyzed all included articles for
      quality and bias using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A
      total of 206 papers were identified, with 11 meeting the inclusion criteria (190
      patients). For T1-2 OPSCC, the aggregate local control rate was 96.3% with an OS
      rate of 95.0%. Rates of prolonged (>12 month) TT and GT dependence were 0.0% and
      5.0% respectively. CONCLUSIONS: This systematic review suggests that TORS offers
      high rates of disease control with low rates of long-term TT or GT dependence in
      T1-2 OPSCC. However, further study is needed to compare TORS outcomes to those of
      traditional therapies.

PMID- 24917390
TI  - Utility of CT after sonography for suspected appendicitis in children:
      integration of a clinical scoring system with a staged imaging protocol.
AB  - To improve diagnosis of pediatric appendicitis, many institutions have
      implemented a staged imaging protocol utilizing ultrasonography (US) first and
      then computed tomography (CT). A substantial number of children with suspected
      appendicitis undergo CT after US, and the efficient and accurate diagnosis of
      pediatric appendicitis continues to be challenging. The objective of the study is
      to characterize the utility of CT following US for diagnosis of pediatric
      appendicitis, in conjunction with a clinical appendicitis score (AS). Imaging
      studies of children with suspected appendicitis who underwent CT after US in an
      imaging protocol were retrospectively reviewed by three radiologists in
      consensus. Chart review derived the AS (range 0-10) and obtained the patient
      diagnosis and disposition, and an AS was applied to each patient. Clinical and
      radiologic data were analyzed to assess the yield of CT after US. Studies of 211
      children (mean age 11.3 years) were included. The positive threshold for AS was
      determined to be 6 out of 10. When AS and US were concordant (N = 140), the
      sensitivity and specificity of US were similar to CT. When AS and US were
      discordant (N = 71) and also when AS >= 6 (N = 84), subsequent CT showed superior
      sensitivity and specificity to US alone. In the subset where US showed neither
      the appendix nor inflammatory change in the right lower quadrant (126/211, 60 %
      of scans), when AS < 6 (N = 83), the negative predictive value (NPV) of US was
      0.98. However, when AS >= 6 (N = 43), NPV of US was 0.58, and the positive
      predictive value of subsequent CT was 1. There was a significant decrease in
      depiction of the appendix on US with patient weight-to-age ratio of >6 (kg/year,
      P < 0.001) and after-hours (1700 -0730 hours) performance of US (P < 0.001).
      Results suggest that the appendicitis score has utility in guiding an imaging
      protocol and support the contention that non-visualization of the appendix on US
      is not intrinsically non-diagnostic. There was little benefit to additional CT
      when AS < 6 and US did not show the appendix or evidence of inflammation; this
      would have avoided CT in 140/211 (66 %) patients. CT demonstrated benefit when AS
      >= 6, suggesting that cases with AS >= 6 and features that limit depiction of the
      appendix on US may be triaged to CT.

PMID- 24917391
TI  - CT and US findings of ovarian torsion within an incarcerated inguinal hernia.
AB  - Inguinal hernia is relatively common in children. Although inguinal hernia is not
      frequently encountered in girls in comparison to boys, there are occasional cases
      of uterine or ovarian herniation in female indirect inguinal hernia. Incarcerated
      ovary in hernia sac has the risk of torsion and strangulation. We present an 8
      year-old girl with painful mass in her left groin. With computed tomography (CT)
      and ultrasonography (US), we made the diagnosis of ovarian strangulation within
      an incarcerated inguinal hernia. Since ultrasound is primarily used for
      evaluation of groin mass, CT findings of an incarcerated inguinal hernia is
      rarely reported. 

PMID- 24917392
TI  - Attributable fraction of alcohol consumption on cancer using population-based
      nationwide cancer incidence and mortality data in the Republic of Korea.
AB  - BACKGROUND: In the Republic of Korea, cancer is the most common cause of death,
      and cancer incidence and mortality rates are the highest in East Asia. As
      alcoholic beverages are carcinogenic to humans, we estimated the burden of cancer
      related to alcohol consumption in the Korean population. METHODS: The cancer
      sites studied were those for which there is convincing evidence of a positive
      association with alcohol consumption: oral cavity, pharynx, esophagus, colon,
      rectum, liver, larynx and female breast. Sex- and cancer-specific population
      attributable fractions (PAF) were calculated based on: 1) the prevalence of
      alcohol drinkers among adults >= 20 years of age in 1989; 2) the average daily
      alcohol consumption (g/day) among drinkers in 1998; 3) relative risk (RR)
      estimates for the association between alcohol consumption and site-specific
      cancer incidence obtained either from a large Korean cohort study or, when more
      than one Korean study was available for a specific cancer site, meta-analyses
      were performed and the resulting meta-RRs were used; 4) national cancer incidence
      and mortality data from 2009. RESULTS: Among men, 3% (2,866 cases) of incident
      cancer cases and 2.8% (1,234 deaths) of cancer deaths were attributable to
      alcohol consumption. Among women, 0.5% (464 cancer cases) of incident cancers and
      0.1% (32 deaths) of cancer deaths were attributable to alcohol consumption. In
      particular, the PAF for alcohol consumption in relation to oral cavity cancer
      incidence among Korean men was 29.3%, and the PAFs for pharyngeal and laryngeal
      cancer incidence were 43.3% and 25.8%, respectively. Among Korean women, the PAF
      for colorectal cancer incidence was the highest (4.2%) and that for breast cancer
      incidence was only 0.2%. Avoiding alcohol consumption, or reducing it from the
      median of the highest 4th quartile of consumption (56.0 g/day for men, 28.0 g/day
      for women) to the median of the lowest quartile (2.80 g/day for men, 0.80 g/day
      for women), would reduce the burden of alcohol-related cancers in Korea.
      CONCLUSIONS: A reduction in alcohol consumption would decrease the cancer burden
      and a significant impact is anticipated specifically for the cancers oral cavity,
      pharynx, and larynx among men in the Republic of Korea.

PMID- 24917394
TI  - In silico approach to inhibition of tyrosinase by ascorbic acid using molecular
      docking simulations.
AB  - Current evidence suggests that endogenous dopamine may act as a neurotoxin
      following its oxidation to an oquinone and reaction with cellular thiols, which
      are neutoxic, which may occur spontaneously or via reaction with tyrosinase or
      some other enzymes. Tyrosinase (E.C. 1.14.18.1) with two cupper ions coordinated
      by three histidines is a bifunctional enzyme that catalyses both the
      hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting
      catechol-containing species to an o-quinone. Therefore, tyrosinase may play a
      role in neuromelanin formation in the brain and could be central to dopamine
      neurotoxicity by contributing to the neurodegeneration associated with
      Parkinson's disease. In the present study, inhibitory effect of ascorbic acid
      against tyrosinase has been investigated and it has shown a remarkable inhibitory
      effect in in vitro assays. Then, the in silico-based experiments established
      through molecular docking calculations and scoring, docking search algorithm, and
      data plotting indicated that ascorbic acid is strong inhibitor of tyrosinase by
      interacting with four amino acid units (histidine 263, serine 282, phenylalanine
      264, and valin 283) in the active site of the enzyme. The compound also had two
      long distant hydrogen bindings with Cu1 and Cu2 with distances of 3.57 and 3.41
      A, respectively, through its O5 atom.

PMID- 24917393
TI  - Identification and functional analysis of a new putative caveolin-3 variant found
      in a patient with sudden unexplained death.
AB  - BACKGROUND: Sudden cardiac death (SCD) is the clinical outcome of a lethal
      arrhythmia that can develop on the background of unrecognized channelopathies or
      cardiomyopathies. Several susceptibility genes have been identified for the
      congenital forms of these cardiac diseases, including caveolin-3 (Cav-3) gene. In
      the heart Cav-3 is the main component of caveolae, plasma membrane domains that
      regulate multiple cellular processes highly relevant for cardiac excitability,
      such as trafficking, calcium homeostasis, signal transduction and cellular
      response to injury. Here we characterized a new putative Cav-3 variant, Cav-3
      V82I, found in a patient with SCD. RESULTS: In heterologous systems Cav-3 V82I
      was expressed at significantly higher level than Cav-3 WT and accumulated within
      the cells. Cells expressing Cav-3 V82I exhibited a decreased activation of
      extracellular-signal-regulated kinases (ERKs) and were more vulnerable to sub
      lethal osmotic stress. CONCLUSION: Considering that abnormal loss of myocytes can
      play a mechanistic role in lethal cardiac diseases, we suggest that the
      detrimental effect of Cav-3 V82I variant on cell viability may participate in
      determining the susceptibility to cardiac death.

PMID- 24917396
TI  - [Reoperative cardiac surgery after previous coronary artery bypass grafting].
AB  - Reoperative cardiac surgery after coronary artery bypass grafting( CABG) has been
      increasing. We reviewed 25 cases of reoperative cardiac surgery after CABG. Re
      CABG was not included in this study. The patients consisted of 15 men and 10
      women. The mean patient age was 74.4+/-6.3 years old. The reoperations were
      performed 6.3+/-5.1 years after CABG. They consisted of 7 aortic valve surgeries,
      2 double valve surgeries, 12 mitral valve surgeries, and 4 total arch
      replacements. Resternotomy was performed in 20 cases, while right thoracotomy was
      performed in 5 cases. Internal thoracic artery( ITA)grafts had been used in 24
      cases, and 22 of them were patent. Fifteen operations were performed under
      cardioplegic arrest with the patent ITA graft clamped from the left pleural
      space, while 5 operations were performed under perfused ventricular fibrillation
      with hypothermia. No differences were observed between the 2 groups in terms of
      cardiopulmonary bypass (CPB) time and peak creatine kinase MB (CK-MB). Operative
      mortality was 4% (1/25). To clamp left internal thoracic artery (LITA) graft from
      the left pleural space is easy and safe. In case clamping the patent graft is
      difficult, perfused ventricular fibrillation with hypothermia is a useful
      alternative. 

PMID- 24917395
TI  - Aldo-keto reductase 1C3 is overexpressed in skin squamous cell carcinoma (SCC)
      and affects SCC growth via prostaglandin metabolism.
AB  - Aldo-keto reductase 1C3 (AKR1C3) is an enzyme involved in metabolizing
      prostaglandins (PGs) and sex hormones. It metabolizes PGD2 to 9alpha11beta-PGF2 ,
      diverting the spontaneous conversion of PGD2 to the PPARgamma agonist, 15-Deoxy
      Delta-12, 14-prostaglandin J2 (15d-PGJ2 ). AKR1C3 is overexpressed in various
      malignancies, suggesting a tumor promoting function. This work investigates
      AKR1C3 expression in human non-melanoma skin cancers, revealing overexpression in
      squamous cell carcinoma (SCC). Effects of AKR1C3 overexpression were then
      evaluated using three SCC cell lines. AKR1C3 was detected in all SCC cell lines
      and its expression was upregulated in response to its substrate, PGD2 . Although
      attenuating AKR1C3 expression in SCC cells by siRNA did not affect growth,
      treatment with PGD2 and its dehydration metabolite, 15d-PGJ2 , decreased SCC
      proliferation in a PPARgamma-dependent manner. In addition, treatment with the
      PPARgamma agonist pioglitazone profoundly inhibited SCC proliferation. Finally,
      we generated an SCC cell line that stably overexpressed AKR1C3 (SCC-AKR1C3). SCC
      AKR1C3 metabolized PGD2 to 9alpha11beta-PGF2 12-fold faster than the parent cell
      line and was protected from the antiproliferative effect mediated by PGD2 . This
      work suggests that PGD2 and its metabolite 15d-PGJ2 attenuate SCC proliferation
      in a PPARgamma-dependent manner, therefore activation of PPARgamma by agonists
      such as pioglitazone may benefit those at high risk of SCC. 

PMID- 24917397
TI  - [Retrospective study on the effect of weekend admission for the treatment of the
      spontaneous pneumothorax].
AB  - Our aim is to evaluate whether outcomes differ by admission day of the week in
      patients with spontaneous pneumothorax. One hundred twenty five patients
      undergoing video-assisted thoracic surgery(VATS) in Fukuoka Tokusyukai Hospital
      from 2007 through 2011 for spontaneous pneumothorax were reviewed. The clinical
      characteristics and outcomes were compared between patients in weekend admission
      and weekday admission groups. Patients were divided in 2 groups based on
      admission between Monday thru Friday vs on Saturday or Sunday. Another 2 groups
      by admission between Sunday thru Thursday vs on Friday or Saturday were also
      examined. Time to operation was significantly shorter for admission on period
      between Sunday thru Thursday compared to admission on Friday or Saturday. But
      there was no difference in the other clinical factors and postoperative outcomes
      between 2 groups. Patients admitted on the weekend proved to experience delayed
      operation, but did not have increased adverse outcomes or longer length of
      hospital stay compared to those admitted on a weekday. No significant "weekend
      effect" for spontaneous pneumothorax was demonstrated by the present study. 

PMID- 24917399
TI  - [Typical bronchial carcinoid with repeated recurrence observed for 17 years after
      radical operation].
AB  - A 68-years-old male patient had been diagnosed as having bronchial carcinoid in
      B2 and right upper lobectomy with systematic hiler and mediastinal
      lymphadenectomy had been performed in 1996. Pathological diagnosis was a typical
      carcinoid (pT1aN0M0, stage I A). In 2004, 4 tumors were found in the trachea,
      right bronchial stump, right main bronchi and right B6 orfice. These were
      diagnosed as typical carcinoids by pathology. In 2005 argon plasma coagration was
      performed.In 2013, a localized recurrence was found in the right S6 by chest
      computed tomography (CT). The segmentectomy of the right S6 was performed. Even
      after radical operation for typical carcinoids, we should conduct long-term
      observation.

PMID- 24917398
TI  - [Pulmonary metastases from colon cancer and occult thyroid cancer in the same
      lobe].
AB  - A 70-year-old man with a history of surgery for colon cancer was found to have
      multiple enlarging pulmonary nodules( 2 in the left lower lobe and 1 in the right
      upper lobe), and was suspected of having pulmonary metastases from colon cancer.
      He underwent left lower lobectomy, and subsequent histopathological examination
      revealed that one was a pulmonary metastasis from colon cancer, and the other was
      a pulmonary metastasis from papillary thyroid cancer. There were no abnormalities
      in the thyroid gland according to computed tomography and ultrasonography
      findings. Therefore, the patient was diagnosed with synchronous pulmonary
      metastases of both colon cancer and occult thyroid cancer in the same lobe. This
      is an exceedingly rare case;to the best of our knowledge, there has been no
      report thus far regarding multiple pulmonary metastases from different primary
      sites. 

PMID- 24917400
TI  - [A new method for reversed bevel technique using single-branched graft in hemi
      arch replacement].
AB  - We describe a reversed bevel technique in hemi-arch replacement with a single
      branched graft that enables long elliptical distal anastomosis and easier
      proximal anastomosis under antegrade systemic perfusion. If the distance between
      the clamped graft and the proximal aorta is too short, it becomes challenging to
      perform the anastomosis by everting the end of the graft. Because we clamp the
      graft at the most distal site, the side branch ends up being located at the
      beveled graft site.This method ensures sufficient surgical view during proximal
      anastomosis. 

PMID- 24917401
TI  - [Mediastinal schwannoma resected through the 10th intercostal space via a
      posterolateral thoracotomy].
AB  - A 64-year-old woman with a mediastinal tumor incidentally found on computed
      tomography( CT) was referred to our hospital. CT and magnetic resonance imaging(
      MRI) showed the tumor had a clear border and was located on the right side of the
      12th thoracic vertebra, spanning the thoracic and abdominal cavities. She was
      suspected of having a benign neurogenic tumor of the mediastinum. She underwent
      tumor resection through the tenth intercostal space via a posterolateral
      thoracotomy. We easily resected the tumor using this approach. Pathological
      examination revealed a benign schwannoma of the mediastinum. Although this
      approach is rarely chosen by thoracic surgery, it is sometimes useful for the
      resection of mediastinal tumors near the diaphragm.

PMID- 24917402
TI  - [Rapid transition from purulent to constrictive pericarditis].
AB  - A 48-year-old woman experienced a high fever and precordial pain. Computed
      tomography revealed pericardial fluid, and she was diagnosed with viral
      pericarditis. The pericardial fluid gradually increased, and she experienced pre
      shock. Pericardial drainage was therefore performed, and the fluid was found to
      be purulent on the 11th day. Pleural effusion and ascites retention, then
      increased, and she was diagnosed with constrictive pericarditis on the 21st day
      by the date of the right ventricular pressure. Excision of the pericardium was
      performed through median sternotomy on the 27th day after the onset. As the
      ventricular diastolic function improved, the heart swelled, and sternal closure
      became impossible. It was finally closed 5 days after the surgery. The patient
      had no recurring infection, and was discharged on the 36th postoperative day.
      Although purulent pericarditis is a rare disease, you should keep in mind that it
      may progress rapidly to constrictive pericarditis. 

PMID- 24917403
TI  - [Redo off-pump coronary artery grafting through left thoracotomy].
AB  - An 80-year-old man successfully underwent reoperative coronary artery bypass
      grafting( CABG) via left thoracotomy without cardiopulmonary bypass. The proximal
      end of the saphenous vein graft( SVG)was connected to the thoracic aorta using an
      automated proximal anastomosis system. Then the SVG routed beneath the pulmonary
      hilum was anastomosed to the high lateral branch and the anterior descending
      artery in a sequential mode. He recovered uneventfully and is free of chest pain
      after redo CABG. In selected patients, redo CABG for the left coronary artery can
      be safely performed through left thoracotomy. 

PMID- 24917404
TI  - [Sternomyelitis caused by delayed tracheal necrosis after thyroidectomy;treatment
      using muscle flap of petoralis major].
AB  - We experienced a rare case of delayed tracheal rupture after thyroidectomy for
      papillary thyroid cancer, and the infection causing sternomyelitis. A 69-year-old
      man presented subcutaneous emphysema after 6 days of total thyroidectomy with
      bilateral cervical and mediastinal dissection for lymph node metastases by
      adverse T sternotomy. He underwent tracheostomy on 10th postoperative day (POD),
      debridement of sternum on 14th POD, and implantation of skin-muscle flap using
      pectolaris major on 43th POD. The flap showed good adaptation and no infectious
      complications recurred, so that he could consequently receive closing procedure
      of tracheostomy on 94th POD.

PMID- 24917405
TI  - [Surgical treatment for traumatic injury of the ascending aorta and aortic arch;
      report of a case].
AB  - We herein report a rare case of surgical treatment for blunt traumatic injury of
      the ascending aorta and aortic arch. A 60-year-old male was crushed by an arm of
      a forklift while working. He suffered from multiple thoracic traumas, including
      injury of the ascending aorta and aortic arch, multiple fractures of the ribs and
      bilateral hemopneumothorax. An emergency surgery for aortic repair was performed
      because there were no other severe hemorrhagic compilations due to organ injures.
      There was a massive hematoma around the aortic arch, and the intimae of several
      parts of the distal ascending aorta and aortic arch were disrupted
      circumferentially. The aorta was replaced with a prosthetic graft from
      sinotubular junction to the aortic arch, between the left common carotid artery
      and the left subclavian artery. The patient's postoperative course was
      uneventful, and he was transferred to a rehabilitation facility on the 13th day
      after surgery.

PMID- 24917406
TI  - [An operative case of a chronic traumatic thoracic aortic aneurysm 16 years after
      a jet skiing crash; report of a case].
AB  - Injury of the thoracic aorta following a major blunt trauma to the chest occurs
      most frequently at the aortic isthmus and more than 80% of such patients die
      within 1st 30 minutes. However, less than 5% of patients survive and later
      develop chronic thoracic aortic aneurysm (TAA). Usually, most cases of chronic
      traumatic TAA have no symptoms for a long time after an accident. We report a
      case of successful repair for a chronic traumatic TAA 16 years after a jet skiing
      crash. A 37-year-old woman complained of left chest pain, back pain, and cough. A
      computed tomography showed a descending TAA, which was 5 cm in a maximum
      diameter. The final diagnosis was chronic traumatic TAA. Thoracic endovascular
      aortic repair (TEVAR) or graft replacement was considered as an operative
      procedure. We performed graft replacement to avoid complications of TEVAR,
      considering her small external iliac arteries. 

PMID- 24917407
TI  - [Leg amputation for severe lower limb ischemia caused by type A acute aortic
      dissection; report of a case].
AB  - A 41-year-old man underwent total arch replacement and aorto-bifemoral bypass
      owing to type A acute aortic dissection complicated by ischemia of both lower
      extremities. Just after the operation, he developed myonephropathic metabolic
      syndrome due to severe ischemia of the right leg, and hemodiafiltration was
      performed. However, the serum potassium was elevated to an uncontrollable level.
      Ligation of the right femoral artery and the right branch of the bypass graft was
      performed one hour after the transfer to intensive care unit (ICU), and the serum
      potassium dropped to a normal level. He underwent amputation of the right lower
      limb above the knee on the 13th postoperative day, and was discharged after long
      term rehabilitation. 

PMID- 24917408
TI  - [Valve plasty for mitral regurgitation caused by partial papillary muscle rupture
      after acute myocardial infarction;report of a case].
AB  - A 58-year-old woman was referred to our hospital because of acute myocardial
      infarction. Percutaneous coronary intervention for total occlusion of the
      circumflex coronary artery was performed successfully. However, she had heart
      failure that was gradually getting worse because of mitral valve regurgitation.
      Therefore, we performed valve plasty using the resection and suture method for
      mitral regurgitation caused by partial papillary muscle rupture. Her
      postoperative course was uneventful, and she was discharged on postoperative day
      26. At 6 months after the operation, her functional status was New York Heart
      Association(NYHA) class I and transthoracic echocardiogram showed no mitral
      regurgitation( MR). 

PMID- 24917409
TI  - [Surgical treatment of coronary sinus orifice atresia; report of a case].
AB  - We report a case of a 69-year-old man with coronary sinus orifice atresia
      incidentally found during mitral and tricuspid valve operation in.
      Preoperatively, a patent left superior vena cava was noted. An abnormal opening
      of the coronary sinus was recognized in the inter-atrial septum of the left
      atrium near the postero-medial commissure of the mitral valve. The coronary sinus
      was absent in the right atrium. A coronary sinus was created by resecting the
      inter-atrial septum of the right atrium, and the abnormal opening of the coronary
      sinus at the left atrium was closed with an autologus pericardial patch.
      Tricuspid annuloplasty was performed with a 30 mm MC3 ring. Postoperative
      coronary sinus flow was confirmed normal by enhanced computed tomography (CT).
      Preoperative recognition of this rare disease is important, especially when the
      surgical candidate has a patent left superior vena cava. 

PMID- 24917410
TI  - [A re-do case of recurrent constrictive pericarditis 35 years after
      pericardiectomy; report of a case].
AB  - Reports of recurrent constrictive pericarditis are scarce. We report a re-do case
      of recurrent constrictive pericarditis 35 years after pericardiectomy. The
      calcified pericardium was thick and severely adhesive. We performed
      pericardiectomy on pump, using Harmonic Scalpel and rib scissors for a safe and
      secure operation. The calcified pericardium looked like a crab's shell. The
      patient was discharged on 14th post-operative day. Long-term follow-up is
      necessary for this patient. 

PMID- 24917411
TI  - [Warfarin effects diminishment by the Clostridium butyricum preparation after
      cardiac surgery; report of a case].
AB  - A 55-year-old gentleman diagnosed with severe aortic insufficiency and
      annuloaortic ectasia underwent modified Bentall procedure using mechanical valve.
      Anticoagulation therapy with warfarin was introduced after surgery, but
      sufficient anticoagulation effect was not achieved with a large amount of dosage.
      After discontinuing the use of the Clostridium butyricum preparation on
      postoperative day 29, sufficient anticoagulationt effect was obtained within
      several days. Clostridium butyricum might change the vitamin K production in the
      intestinal bacterial flora and attenuated the anticoagulation effect of warfarin.

PMID- 24917412
TI  - [Thymoma showing enlargement and reduction in size with inflammatory
      events;report of a case].
AB  - An 87-year-old male who had gone surgery for bladder cancer in 1994, was pointed
      out a mass in the anterior mediastinum by follow up in May 2007. Thereafter, no
      change in size of the mass had been noted. In February 2011, however, enlargement
      of the tumor with inflammation and right pleural effusion was found. While
      waiting for surgery, the patient experienced regression of the tumor, and the
      pleural effusion disappeared. Tumor excision and combined resection of the lung
      and pericardium were performed. Postoperative histopathological findings showed
      Masaoka stageI thymoma of type B1 according to the World Health Organization(
      WHO) Classification. Granulation due to old inflammation, precipitation of
      cholesterin crystals, hemorrhages, and necrosis were noted in the tumor. In the
      differential diagnosis of tumors in the anterior mediastinum with spontaneous
      regression, thymoma should be considered.

PMID- 24917413
TI  - [Re-operation for relapsed thymic carcinoid; report of a case].
AB  - A 68-year-old male patient underwent extended thymectomy via median sternotomy, 4
      years ago. The pathological diagnosis was thymic atypical carcinoid having
      invaded the pleura and vessel. During follow-up, the new nodular shadows in the
      anterior mediastinum were pointed out by a chest computed tomography (CT) scan,
      40*38 mm and 11*10 mm in size. We performed again tumor resection and resection
      of pleural disseminations. The patient was free of clinically evident recurrence
      3 years after treatment. 

PMID- 24917414
TI  - Effects of flecainide on left ventricular pressure gradient and symptoms in
      obstructive hypertrophic cardiomyopathy: a comparison of flecainide and
      disopyramide.
AB  - It remains unclear whether flecainide, a Class I antiarrhythmic drug, improves
      left ventricular pressure gradient (LVPG) or symptoms in patients with
      obstructive hypertrophic cardiomyopathy (HCM). Our study evaluated the long-term
      efficacy of flecainide, compared to disopyramide, when administered orally, on
      LVPG and symptoms in obstructive HCM patients. Among 164 obstructive HCM
      patients, 15 were administered oral flecainide therapy and 33 administered oral
      disopyramide therapy. LVPG declined from 79.8 +/- 36.6 to 39.2 +/- 36.7 mmHg (p =
      0.003) after flecainide therapy and from 74.5 +/- 26.4 to 31.4 +/- 24.8 mmHg (p <
      0.001) after disopyramide therapy. The percent reduction in LVPG was -47.9 +/-
      43.2 % in patients treated with flecainide, comparable to the results for those
      treated with disopyramide (-57.1 +/- 33.0 %; p = 0.425). We found no significant
      differences in improvement in NYHA functional class between patients treated with
      flecainide and those treated with disopyramide (p = 0.331). Patients treated with
      flecainide exhibited no significant adverse side effects, and there was no need
      for myectomy or alcohol septal ablation to reduce LVPG and symptoms. Improvements
      in LVPG and symptoms were similar in patients treated with flecainide and
      patients treated with disopyramide, suggesting that flecainide is a potentially
      useful alternative for symptomatic obstructive HCM patients, particularly those
      with disopyramide-induced vagolytic side effects, narrow angle glaucoma, or
      prostatic hyperplasia and pre-existing urination difficulties. Our data must be
      viewed with caution, however, in view of the small number of study patients.
      Flecainide therapy will require further proof of safety before it can be
      routinely recommended in patients with symptomatic obstructive HCM. 

PMID- 24917416
TI  - Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer
      immunotherapy.
AB  - Significant enthusiasm currently exists for new immunotherapeutic strategies:
      blocking the interaction between programmed death-1 receptor on T-cells and
      programmed death-ligand 1 on tumor cells to boost immune system stimulation to
      fight cancer. Immunomodulation with the antiprogrammed death-1/programmed death
      ligand 1 monoclonal antibodies has shown to mediate tumor shrinkage and extend
      overall survival from several pivotal phase I/II studies in melanoma, renal cell
      carcinoma, and non-small cell lung cancer. This has prompted multiple large
      ongoing phase III trials with the expectation for fast-track FDA approvals to
      satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway
      that are in clinical trials fall into two major categories, namely antiprogrammed
      death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death
      ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C. We
      reviewed the clinical efficacy and safety of each compound based upon major
      registered clinical trials and published clinical data. Overall, response rate of
      more than 20% is consistently seen across all these trials, with maximal response
      of approximately 50% achieved by certain single antiprogrammed death-1 agents or
      when used in combination with cytotoxic T-lymphocyte antigen-4 blockade. The
      responses seen are early, durable, and have continued after treatment
      discontinuation. Immune-related adverse events are the most common side effects
      seen in these clinical trials. Overall, the skin and gastrointestinal tract are
      the most common organ systems affected by these compounds while hepatic,
      endocrine, and neurologic events are less frequent. These side effects are low
      grade, manageable, and typically resolve within a relatively short time frame
      with a predictable resolution pattern given proper management. We therefore
      propose detailed guidelines for management of major immune-related adverse events
      that are anticipated with antiprogrammed death-1/programmed death-ligand 1
      therapies based on general experience with other monoclonal antibodies and the
      established management algorithms for immune-related adverse events for cytotoxic
      T-lymphocyte antigen-4 blockade with ipilimumab. We anticipate that the
      antiprogrammed death-1 strategy will become a viable and crucial clinical
      strategy for cancer therapy.

PMID- 24917415
TI  - Exploring secular changes in the association between BMI and waist circumference
      in Mexican-origin and white women: a comparison of Mexico and the United States.
AB  - OBJECTIVES: BMI and waist circumference (WC) tend to be highly correlated, but
      changes in lifestyle behaviors may promote greater accumulation of abdominal fat
      for the same BMI in recent years. We examined secular shifts in BMI and WC
      distributions, and investigated whether WC for a given BMI has changed over time
      among Mexican-origin women in Mexico and the US, and in US white women as a
      comparison. METHODS: Nationally representative surveys for women aged 20-49 years
      from Mexico (1988, 1999, and 2012) (n = 37,116) and the US (1988-1994, 1999-2002,
      and 2007-2010) (n = 6,985) were used. Quantile regressions estimated age-adjusted
      changes in BMI and WC across years; linear regression tested changes in mean WC
      over time, adjusting for age and BMI. RESULTS: In all women, BMI and WC at most
      centiles increased over time. WC was also significantly higher over time for the
      same BMI, though the increase was largest in Mexican women. For example, WC was
      6.7 cm (standard error (SE): 0.17, P < 0.0001) higher in 2012 than in 1999 among
      Mexican women, holding age and BMI constant. Estimates were smaller in magnitude
      for Mexican-American and white women (~3 cm, P < 0.01), even when comparing over
      a longer timeframe (1988-1994 to 2007-2010). In all groups, WC adjusted for BMI
      increased to a larger extent among younger cohorts. CONCLUSION: WC for the same
      BMI has increased in Mexican-American, white, and Mexican women of reproductive
      age. These patterns may have implications for future cardio-metabolic burden in
      Mexico and the US.

PMID- 24917417
TI  - Transamidation of gluten proteins during the bread-making process of wheat flour
      to produce breads with less immunoreactive gluten.
AB  - Due to an increasing incidence of celiac disease (CD) and other gluten-related
      disorders, different gluten-free breads have been developed using starches and
      additives as a substitute for gluten. Thus, patients miss not only the taste and
      aroma of wheat bread but also risk their sensitive intestines. Therefore,
      modifying gluten to avoid an immune response in CD and its application to baking
      is in progress. The aim of the study was to enzymatically modify gluten on wheat
      flour, during bread-making avoiding the use of additives, to reduce
      immunoreactivity, preserving its properties. Microbial transglutaminase (mTG) or
      chymotrypsin (ChT) was used to bind lysine or valine to gluten proteins in a
      model system. The best conditions were directly applied to wheat flour for bread
      making with and without punching at 45 min. Subsequently, the rheological
      properties of the doughs, specific volume of the loaves, immunoreactive gluten
      content and modification of the extracted proteins were evaluated. ChT-treated
      breads presented a better appearance with a more homogeneous crumb, higher
      specific volume values (3.34-4.25 cm(3) g(-1)) and higher reactive gluten
      reduction (up to 71%) than the mTG-treated ones (1.23-2.66 cm(3) g(-1)) with only
      a 42% reactive gluten reduction. Thus, transpeptidation during bread-making is a
      promising technology, although it is necessary to improve the modification
      process to obtain the reactive gluten reduction required in breads for the
      treatment of CD patients and other gluten-related disorders. 

PMID- 24917418
TI  - Surgery of the femur in HIV positive patients: a retrospective review from 2005
      to 2011.
AB  - BACKGROUND: There are an estimated 6,900 people with HIV living in Ireland. There
      is a significant prevalence of femoral osteonecrosis and risk factors for
      osteoporotic fractures. With this potential, increasing surgical workload, it is
      important to assess surgical demand and audit outcomes. METHODS: The hospital's
      electronic records were examined. Between January 2005 and August 2011, 17
      femoral surgeries were identified in seven patients. Patient records were
      retrospectively reviewed. RESULTS: Elective operations undertaken were eight hip
      replacements and one nail dynamisation. Eight emergency operations were
      undertaken: two DHS, one plating, one nailing, one revision nailing, two incision
      and drainages and one biopsy. All procedures were carried out using appropriate
      safety guidelines. Indications for surgery included femoral head osteonecrosis (n
      = 7), osteomyelitis (n = 3), proximal femoral fracture (n = 2), femoral shaft non
      union (n = 1), dynamisation of a nail (n = 1), osteoarthritis (n = 1), fractured
      femur (n = 1), and revision nailing (n = 1). For two procedures the patient was
      not on highly active anti-retroviral treatment. All elective patients had CD4
      counts greater than 200 pre-operatively. Six patients had undetectable viral
      loads. Of the eight emergency procedures, four procedures had no preoperative
      immune status recorded. Complications recorded were three non-unions, one nail
      fracture, one lesser trochanter fracture and recurrence of osteomyelitis. No
      surgical site infections were recorded. CONCLUSIONS: Complications were not
      related to immune status. The rate of surgical site infection in both elective
      and emergency procedures was low. The elective surgery patients can safely
      receive orthopaedic treatment in their regional orthopaedic unit. Due to the high
      non-infectious complication rates recorded in the emergency group, transfer to a
      tertiary facility with infectious disease expertise is advised.

PMID- 24917419
TI  - Malignant melanoma: factors affecting the surgical interval from excision biopsy
      to definitive surgical management.
AB  - INTRODUCTION: Surgery remains the mainstay of treatment for malignant melanoma.
      Despite previous studies examining the surgical interval (SI) between the
      diagnostic excision biopsy (DEB) and definitive surgical management there remains
      few guidelines regarding an optimal time interval. The aim of this study was to
      determine the SI between DEB and definitive surgery and elucidate factors
      associated with delays in management of malignant melanoma. METHODS: A
      retrospective study of 107 consecutive patients who had a DEB and subsequent wide
      local excision between January 2011 and June 2012 was performed. Mode of referral
      and dates of diagnostic biopsy/definitive surgery were documented. Patient
      demographics and tumour characteristics were reviewed. RESULTS: The mean age was
      59.6 years, and male:female ratio was 1:1.3. Median duration of the SI was 41 +/-
      27 days (range 6-137 days). The SI was increased when dermatologists performed
      the DEB as opposed to general surgeons (p = 0.035). The anatomic location of the
      lesion predicted the SI, with lesions of the head/neck undergoing definitive
      excision 48 +/- 32.3 days after DEB vs. 37.5 +/- 22.6 days for all other sites (p
      = 0.001). Neither demographic factors nor histopathological prognostic features
      affected the SI. Reasons for a prolonged SI included referrals to different
      services and time for pre-operative planning. CONCLUSIONS: Significant variations
      were noted in the SI predominantly accounted for by mode of referral and location
      of the malignant melanoma. Further investigation is required to elucidate factors
      affecting the SI and its subsequent effect on patient outcomes.

PMID- 24917420
TI  - Quality of life, fatigue and local response of patients with unstable spinal bone
      metastases under radiation therapy--a prospective trial.
AB  - BACKGROUND: To evaluate the local response according to stability after
      radiotherapy (RT) with a special focus on quality-of-life (QoL), fatigue, pain
      and emotional distress in patients with unstable spinal bone metastases. METHODS:
      In this prospective trial, 30 patients were treated from September 2011 until
      March 2013. The stability of osteolytic metastases in the thoracic and lumbar
      spine was evaluated on the basis of the Taneichi-score after three and six
      months. EORTC QLQ-BM22, EORTC QLQ-FA13, and QSC-R10 were assessed at baseline,
      and three months after RT. RESULTS: After 3 months, 25% (n = 6) and after 6
      months 33.3% (n = 8) were classified as stable. QoL, fatigue, and emotional
      distress showed no difference over the course. The pain response 3 months after
      RT showed a significant difference (p < 0.001). Pathological fractures occurred
      in 8.3% of the patients (n = 2) within six months following RT. CONCLUSIONS: Our
      trial demonstrated that RT can improve stability in one third of patients over a
      6-months period with unstable spinal metastases. Importantly, for these patients
      pain relief was detected but RT had no impact on QoL, fatigue, and emotional
      distress. TRIAL REGISTRATION: Clinical trial identifier NCT01409720.

PMID- 24917421
TI  - The effect of stunning methods and season on muscle texture hardness in Atlantic
      salmon (Salmo salar L.).
AB  - Commercially collected records of Atlantic salmon (Salmo salar L.) muscle texture
      hardness were used to evaluate the effect of slaughter procedures and seasonality
      on texture quality. A database collected by Marine Harvest(r) contained flesh
      hardness records of Atlantic salmon slaughtered at processing plants in Norway
      from summer 2010 to summer 2011. The fish were slaughtered either by (1)
      percussion followed by automated bleeding ("Percussive") or (2) live chilling
      with exposure to carbon dioxide (CO2 ) followed by manual severing gill arches
      and bleeding ("CO2 ") or (3) live chilling with exposure to CO2 followed by
      percussive stunning and at the end automated bleeding ("CO2 .percussive").
      Hardness in salmon muscle cutlets was measured in Newtons (N) by Materials
      Testing Machine Zwick 500N. The hardness in salmon varied significantly over the
      study period (P < 0.05, mixed effect model) and showed the softest value of 21.2
      (+/- 0.7) Newton (N) in summer 2011 and hardest 24.1 (+/- 0.2) N in autumn 2010.
      Slaughter procedures had a significant effect on salmon muscle hardness (P <
      0.05, mixed effect model), where percussion followed by automated bleeding
      resulted in the hardest value (24.0 +/- 0.4 N) as compared with CO2 stunning
      (21.8 +/- 0.2 N) and combination of CO2 and percussive stunning (23.1 +/- 0.15
      N). CO2 is suspected as a causal factor in accelerated postmortem softening of
      the salmon muscle. PRACTICAL APPLICATION: Commercial use of CO2 in combination
      with live chilling results in accelerated postmortem softening of the muscle
      tissue in salmon and should be avoided.

PMID- 24917423
TI  - Oscars, Emmys, Tonys, and Tanners.

PMID- 24917424
TI  - Shiga-toxin genes and genetic diversity of Escherichia coli isolated from
      pasteurized cow milk in Brazil.
AB  - This study evaluated the genetic similarity and prevalence of the stx1, stx2,
      eae, and ehxA genes in Escherichia coli isolated from pasteurized cow milk.
      Eighty-seven E. coli isolates from pasteurized cow milk from 22 dairies located
      in northwestern Parana state, Brazil, were analyzed. Genetic similarity was
      evaluated using enterobacterial repetitive intergenic consensus sequence
      polymerase chain reaction (ERIC-PCR) and repetitive extragenic palindromic
      sequence PCR (REP-PCR). E. coli isolates were also analyzed by PCR to investigate
      the presence of the stx1, stx2, eae, and ehxA genes. ERIC-PCR and REP-PCR
      clustered 87 bacterial isolates in 76 and 81 genomic profiles, respectively. Both
      techniques revealed high genetic diversity among the E. coli isolates, confirming
      the possibility of their use in epidemiological studies. The stx1, stx2, eae, and
      ehxA virulence genes were not detected in E. coli isolates, indicating a low
      prevalence of Shiga toxin-producing E. coli in milk produced in the region
      studied. PRACTICAL APPLICATION: Knowledge about the presence of diarrheagenic
      Escherichia coli in pasteurized milk is important developing and implementing
      control measures in milk and dairy production.

PMID- 24917426
TI  - Low rates of adjuvant radiation in patients with nonmetastatic prostate cancer
      with high-risk pathologic features.
AB  - BACKGROUND: The 2013 American Urological Association/American Society for
      Radiation Oncology consensus guidelines recommend offering adjuvant radiotherapy
      (RT) after radical prostatectomy in patients with high-risk pathologic features
      for recurrence. In the current study, the authors examined practice patterns of
      adjuvant RT use in patients with elevated pathologic risk factors over a time
      period spanning the publication of supporting randomized evidence. METHODS: Using
      the National Cancer Data Base, a total of 130,681 patients were identified who
      underwent surgical resection for prostate cancer between 2004 and 2011 with at
      least 1 of the following pathologic risk factors for early biochemical failure:
      pT3a disease or higher, positive surgical margins and/or lymph node-positive
      disease. Using multivariable logistic regression, the authors examined factors
      associated with adjuvant RT use including patient, clinical, demographic, and
      temporal characteristics. RESULTS: Adjuvant RT was administered to 9.9% of the
      patients with at least 1 pathologic risk factor. Use of adjuvant RT did not
      change over the study period (P  = .23). On multivariable analysis, we found that
      patients treated at high-volume surgical facilities were less likely to receive
      adjuvant RT (15.9% vs 7.8%; odds ratio, 0.58 [95% confidence interval, 0.50
      0.65]; P < .0001). Older age, comorbidities, black race, lower income, and lower
      population density were also associated with lower rates of adjuvant RT.
      CONCLUSIONS: Use of adjuvant RT is uncommon and remained unchanged between 2004
      and 2011. Patients treated at high-volume surgical facilities are less likely to
      receive adjuvant RT, irrespective of margin status.

PMID- 24917427
TI  - Detection of bacteraemia and host response in healthy neonatal foals.
AB  - REASONS FOR PERFORMING THE STUDY: Neonatal sepsis is a common problem in foals
      and is a primary cause of death in the post natal period. Transient bacteraemia
      and subsequent host responses have not been described in the equine neonate.
      OBJECTIVES: The primary objective of this study was to determine if transient
      bacteraemia occurs in foals within the first 72 h of life. Additional objectives
      included description of bacterial organisms associated with transient bacteraemia
      and concurrent cytokine gene expression in healthy foals. STUDY DESIGN:
      Prospective observational study in healthy foals. METHODS: Blood was aseptically
      collected for bacterial culture from observed spontaneously born foals at birth
      and 1, 2, 3, 4, 8, 12, 24, 48 and 72 h following birth. Samples taken at birth,
      4, 12, 24, 48 and 72 h were analysed for interferon gamma (IFNgamma), interleukin
      (IL)-1, IL-2, IL-6, IL-8, IL-10, IL-18 and monocyte chemotactic protein 1 (MCP1)
      cytokine gene expression quantified by RT-PCR. RESULTS: Bacteria were cultured
      from 9 of 70 samples submitted for blood culture. The positive samples were from
      4 of the 7 foals, all of which remained healthy throughout and subsequent to the
      study. All positive blood cultures were from blood samples obtained at 12 h of
      age or earlier and IL-10 elevation coincided with positive blood cultures in
      healthy foals. Cytokine gene expression fluctuated with age. CONCLUSIONS:
      Positive blood cultures suggest transient bacteraemia may occur in healthy foals
      early in the post natal period. Age corrected normal values may be necessary to
      interpret cytokine concentration in diseased populations.

PMID- 24917429
TI  - Biological threat detection in the air and on the surface: how to define the
      risk.
AB  - The improvements in the existing methods of rapid detection and biological
      pathogen surveillance are still needed. The new spectroscopic methods that rely
      on the unique structural features and intrinsic fluorescence of microorganisms
      are well fitted for monitoring the spread of airborne biological agents or their
      reagentless detection in the air, and these methods may bring a new quality to
      bioaerosols remote detection. This review describes the problem of the confidence
      in the environmental testing results that may affect clearance standard, sampling
      techniques, and the estimation of risk of human exposure to the low
      concentrations of harmful microorganisms during bioterrorist event or naturally
      occurring outbreaks. Higher recovery efficiency of dangerous biological agents
      from the air and contaminated surfaces would enable more reliable environmental
      human risk exposure assessment. 

PMID- 24917428
TI  - Role of osteopontin in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystemic disease, caused by a
      variety of factors, which lead to immunological abnormalities. Osteopontin (OPN)
      is a pleiotropic protein, important in bone remodeling and immune system
      signaling. OPN, produced by various cells, including immune cells, plays a key
      role in regulating T-helper 1/T-helper 2 balance, stimulating B lymphocytes to
      produce antibodies, regulating macrophages, neutrophils and inducing dendritic
      cells. OPN expression is influenced by genetic polymorphisms of its promoter,
      hormones and cytokines. Over expression of OPN has been associated with the
      pathogenesis of immune-mediated diseases. OPN has been implicated in the
      development of murine model of lupus and in humans with SLE. In this review, I
      will present current state of research on the role of OPN and OPN gene
      polymorphisms in pathogenesis and clinical course of SLE. A better understanding
      of the role of OPN in SLE will contribute to more precise diagnosis and treatment
      of the disease. 

PMID- 24917431
TI  - [Not Available].

PMID- 24917430
TI  - Rapid temperature-dependent wound closure following adipose fin clipping of
      Atlantic salmon Salmo salar L.
AB  - Three groups of Atlantic salmon were kept at a constant temperature of 4, 10 and
      14  degrees C. The adipose fins were removed; six fish/group were sampled at 11
      subsequent time points post-clipping. Samples were prepared for histopathological
      examination to study the course of re-epithelization. A score sheet was developed
      to assess the regeneration of epidermal and dermal cell types. Wounds were
      covered by a thin epidermal layer between 4 and 6 h post-clipping at 10 and 14 
      degrees C. In contrast, wound closure was completed between 6 and 12 h in fish
      held at a constant temperature of 4  degrees C. By 18 h post-clipping,
      superficial cells, cuboidal cells, prismatic basal cells and mucous cells were
      discernible in all temperature groups, rapidly progressing towards normal
      epidermal structure and thickness. Within the observation period, only minor
      regeneration was found in the dermal layers. A positive correlation between water
      temperature and healing rates was established for the epidermis. The rapid wound
      closure rate, epidermal normalization and the absence of inflammatory reaction
      signs suggest that adipose fin clipping under anaesthesia constitutes a minimally
      invasive method that may be used to mark large numbers of salmon presmolts
      without compromising fish welfare. 

PMID- 24917432
TI  - Body shape and psychiatric diagnosis revisited.
AB  - Abstract Introduction. Body shape has been aim of study by Medicine throughout
      centuries to find connections between shapes and illnesses. Methods. The
      objective of this systematic review was to understand the origin, as well as
      update empirical research, of body constitution. Results. The study of body
      constitution and of some other groups of physical signs (such as minor physical
      anomalies or joint hypermobility) provides insights into the biology of mental
      disorders that may result in a greater understanding of its aetiology, treatment,
      and prevention. Discussion. We discuss the role of body constitution in order to
      support psychiatric nosology, especially in differential diagnosis, through an
      overall or holistic "body and mind" perception. 

PMID- 24917433
TI  - Anxiety disorders as a risk factor for subsequent depression.
AB  - Abstract Introduction. Patients with comorbid depression and anxiety disorders
      have a higher suicide risk, increased social and vocational dysfunction and more
      severe and refractory illness. Methods. This paper reviews the studies examining
      the temporal relationship between onset of anxiety disorders and depression.
      Results. The highest rates of subsequent depression have been found in
      generalized anxiety disorder, followed by panic disorder and social anxiety
      disorder. The largest numbers of studies have been done on social anxiety
      disorder. Panic attacks, separation anxiety disorder and specific phobia also
      have an association with higher rates of subsequent depression in a limited
      number of studies. Conclusion. Further studies are needed to investigate whether
      treatment and treatment outcomes in anxiety disorders has an effect on the risk
      for developing subsequent depression. 

PMID- 24917434
TI  - Childhood trauma and pain medication prescription in adulthood.
AB  - Abstract Objective. In this study, we examined the relationships between five
      types of self-reported trauma in childhood and the prescription of pain
      medications in adulthood. Methods. Using a cross-sectional sample of convenience,
      we surveyed 80 internal medicine outpatients with regard to five types of
      childhood trauma (i.e. sexual, physical, emotional abuses; physical neglect; the
      witnessing of violence). We then retrospectively examined the medical record of
      each participant for active prescriptions of pain medications during the
      preceding 4 weeks (i.e. narcotic analgesics, non-steroidal anti-inflammatory
      drugs or NSAIDS, "other" pain medications). Results. We found that the number of
      different types of abuse in childhood correlated with NSAID prescriptions,
      "other" pain medication prescriptions, and the total number of prescribed pain
      medications-but not with narcotic analgesic prescriptions. Also, no individual
      form of childhood trauma exceeded the others in contribution. Conclusions. While
      a greater number of different types of childhood trauma demonstrate an
      association with a greater number of different pain medications prescribed,
      according to findings in the medical record, there is no associated increase in
      the prescription of narcotic analgesics. We discuss the potential implications of
      these findings. 

PMID- 24917435
TI  - Long-term effectiveness of aripiprazole in adolescents and young adults with
      bipolar disorder: A naturalistic study.
AB  - Abstract Objective. The purpose of this study was to investigate the long-term
      effectiveness of aripiprazole in Taiwanese samples of adolescents and young
      adults with bipolar disorders. Methods. This investigation comprises a 24-week,
      observational, prospective study. A total of 28 patients with bipolar I disorder,
      diagnosed using the Mini International Neuropsychiatric Interview, were
      administered aripiprazole. Effectiveness was assessed by the change from the
      baseline in Clinical Global Impression Scale (CGI), Brief Psychiatric Rating
      Scale (BPRS) and The World Health Organization Quality of Life questionnaire
      (WHOQOL). Results. The sample comprised 19 males and nine females with a mean
      (SD) age of 18.5 (3.3) years. The diagnosis was bipolar I disorder with manic (n
      = 8), depressive (n = 6) and mixed (n = 14) episodes. Eighteen patients (64.3%)
      discontinued aripiprazole prematurely. The CGI severity, BPRS total score
      improved significantly from the baseline to the endpoint. Conclusion.
      Aripiprazole led to clinically meaningful improvement of global symptoms in
      adolescents and young adults with bipolar disorder. However, discontinuation of
      medication within 6 months was high. Whether aripiparzole benefits patients with
      manic episodes more than those with depressive or mixed episodes warrants further
      investigation. 

PMID- 24917436
TI  - Comparison of DRD2 rs1800497 (TaqIA) polymorphism between schizophrenic patients
      and healthy controls: Lack of association in a Turkish sample.
AB  - Abstract Objective. The association of DRD2 rs1800497 (TaqIA) polymorphisms and
      schizophrenia has been studied in a number of populations, but the results are
      contradictory. We aimed to define Taq IA allelic differences between
      schizophrenic and healthy subjects. Methods. The schizophrenic group consisted of
      99 schizophrenic inpatients, diagnosed and treated at Gazi University Hospital
      Psychiatry Service, the healthy group was composed of 109 subjects who did not
      suffer from any psychiatric or organic diseases. High molecular weight genomic
      DNAs were prepared from peripheral venous blood cells by using proteinase K
      digestion followed by salt extraction method. Target DNA amplification of DRD2
      gene (Taq1A, 310-bp region) was performed by polymerase chain reaction (PCR) with
      the primers 5014 and 971. Results. Of the 208 subjects involved in the study,
      98.6% had A1 allele (hetero- or homo-zygote) and 1.4% had A2 allele (homozygote).
      While all schizophrenia patients had A1 allele, 97.2%, of the healthy subjects
      (n=106) had A1 allele and there was no significant difference between the groups.
      Conclusion. This study was the first study related to DRD2 polymorphism conducted
      in a Turkish schizophrenic patient sample. A great percentage of our sample has
      A1 allele. Our study could not find a significant association between
      schizophrenia and DRD2 rs1800497 polymorphism. 

PMID- 24917437
TI  - Alteration of serum bilirubin level in schizophrenia.
AB  - Abstract Objective. Alteration of serum bilirubin level in acute episodes of
      psychosis in patients with schizophrenia has been reported but the pattern of
      this alteration is controversial. Methods. Patients diagnosed as schizophrenia
      (162, group S) or bipolar disorder (155, group B) entered the study. The control
      group consisted of 95 patients admitted to cardiac care unit who had no personal
      or family history of major psychiatric disorders. Pre- and post-admission levels
      of bilirubin were measured and compared within and between the groups. Patients
      were examined to exclude all other causes of hyperbilirubinemia. Group S and B
      participants were also evaluated using positive and negative syndrome subscale
      (PANSS) both at admission and discharge. Results. The mean admission bilirubin
      levels of all the groups were in the normal range (significantly higher in group
      S than groups B and C) and were affected by the score of general psychopathology
      subscale rather than the scores of positive symptoms subscale. Conclusions.
      Although bilirubin decreased in all three groups at discharge, the rate of
      decrease was significantly higher in group S. The reason for this is not clear
      and needs further study. 

PMID- 24917438
TI  - Elevated salivary alpha-amylase and cortisol levels in unremitted and remitted
      depressed patients.
AB  - Abstract Objective. Major depressive disorder (MDD) is often associated with
      dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis via chronic
      stress. Psychosocial stress-induced activation of salivary alpha-amylase (sAA)
      represents sympathoadrenal medullary system (SAM) activity, and sAA has become an
      emerging biomarker for sympathetic nervous system activity. In contrast to
      salivary cortisol, sAA has been less extensively studied in depressed patients.
      The present study sought to address this problem by measuring sAA and salivary
      cortisol levels in patients with major depressive disorder. Methods. The authors
      recorded Spielberger State-Trait Anxiety Inventory (STAI) scores along with,
      levels of sAA and salivary cortisol in 28 patients with unremitted major
      depressive disorder, 43 remitted patients and 103 healthy volunteers. Results.
      STAI (State or Trait) measurements in unremitted patients with MDD were
      significantly increased compared with healthy controls and remitted patients. SAA
      and cortisol levels in unremitted patients were also significantly elevated
      compared to controls and remitted patients. Finally, sAA levels were
      significantly correlated with HRSD in unremitted patients with MDD. Conclusion.
      These preliminary results suggest that sAA may be a state-dependent marker of
      major depressive disorder in addition to salivary cortisol. 

PMID- 24917439
TI  - Telephone-based nursing strategy to improve adherence to antipsychotic treatment
      in schizophrenia: A controlled trial.
AB  - Abstract Objective. Adherence to prescribed antipsychotic medication is a major
      factor in achieving optimal long-term clinical outcomes. The aim of this study
      was to evaluate the impact of a telephone-based strategy provided by a nurse on
      adherence to antipsychotic treatment among patients with schizophrenia. Methods.
      A total of 928 clinically stable outpatients with schizophrenia were randomized
      to receive a monthly telephone call by a nurse or routine clinical care.
      Telephone calls were performed at weeks 4, 8, and 12, consisting of a
      standardized interview to detect and assess therapeutic adherence and subjective
      attitude towards medication. Patients were followed for 4 months. A cut-point of
      >= 60% of prescribed dose was used to classify patients as being adherent.
      Results. At week 16, a significantly higher percentage of patients who received a
      telephone-based follow-up (96.7%, n = 410) were classified as adherent compared
      to the control group (91.2%, n = 402) (P = 0.0007). Patients in the intervention
      group were significantly more likely to be adherent than control group (adjusted
      OR = 3.3 95% CI 1.6-6.6, P = 0.0001). Conclusions. Telephone-based nursing
      strategy showed a significant improvement in adherence to antipsychotic drugs.
      Further studies are necessary to confirm if this kind of intervention could be a
      complementary strategy to optimize adherence in patients with schizophrenia. 

PMID- 24917440
TI  - Validity of the self-reported smoking status of schizophrenia patients, taking
      gender-related differences into consideration.
AB  - Abstract Objective. It is unclear whether self-reported smoking status reflects
      the true smoking status in schizophrenia patients. This study aims to evaluate
      the consistency in smoking status in schizophrenia patients, as determined using
      self-reported questionnaires and objective measurements, while considering gender
      related differences. Methods. The study involved 158 Japanese schizophrenia
      patients (79 men and 79 women), who were diagnosed according to DSM-IV-TR
      criteria. The patients answered questions about their smoking status and daily
      cigarette consumption. The carbon monoxide (CO) level in the expired air was
      measured to confirm the self-reported answers. We descriptively analysed the data
      and assessed the proportion of results showing consistency between the self
      reported smoking status and measured CO levels. Results. The self-reported
      smoking status was consistent with the objective measurement results in both
      genders. Among the various cut-off CO levels considered, 7 ppm was found to be
      the optimal level in both men and women. Conclusions. Our study showed that self
      reporting is a reliable method for evaluating the smoking status of schizophrenia
      patients, regardless of gender. However, for precise assessment on the basis of
      CO levels in expired air, lower cut-off points may be better than the recommended
      ones. 

PMID- 24917441
TI  - The self-assessment Global Quality of Life scale: Reliability and construct
      validity.
AB  - Abstract Objective. The aim was to establish psychometric properties of the
      Global Quality of Life Scale (GQL) for people with severe mental illness.
      Methods. GQL is a stand-alone visual analogue scale included in "The Quality
      Star", a minimal platform for clinical follow-up and efficiency documentation of
      mental health services in eight dimensions widely used in Sweden. Validating
      instruments included MANSA, Inventory of Problem and Solutions, Consumer
      Satisfaction Rating Scale, Perceived Global Distress, health screening using UKU
      Side Effect Rating Scale, GAF, and Perceived Global Burden (for next of kin).
      Test-retest reliability of the GQL was examined between ratings at quarterly
      intervals during 1 year. Results. There were three main results: test-retest
      reliability at quarterly intervals was very satisfactory, concurrent validity
      with the initial item of life satisfaction scale of MANSA, "Life as a whole", was
      demonstrated and finally content validity was clarified by associations with a
      number of validating measures from several contexts in three studies. Conclusion.
      GQL have acceptable psychometric properties and is valid for serious mental ill
      persons. Its use as easy-to-use instrument for screening of perceived global
      quality of life was supported. 

PMID- 24917442
TI  - Mixed anxiety and depressive disorder before and after psychodynamic group
      psychotherapy: a 1-year follow-up study.
AB  - Abstract Objective. The aim of our study was to observe the outcome of MADD in
      comparison with depressive (DD) and anxiety (AD) disorders. Method. Patients
      treated with 12 weeks of group psychodynamic psychotherapy in a psychiatric day
      care ward were examined using SCAN 2.1 at admission and 1 year after admission.
      Treatment was indicated on the basis of diagnosis of ICD-10 - F4-F6. A total of
      139 patients were included, 110 (79.1%) of whom were examined at the follow-up
      point. Results. The prevalence of MADD increased from 22.7% at the baseline to
      33.6% at the end. The outcome of MADD was statistically different from the
      outcome of DD (chi(2)=18.4, P=0.0025), but not different from the outcome of
      comorbid DD and AD (chi(2)=1.8, P=0.84), nor generalized anxiety disorder
      (chi(2)=8.1, P=0.15), nor other AD (chi(2)=5.3, P=0.38). Conclusion. MADD is a
      useful diagnosis of a transitional or residual form of comorbid DD and AD in some
      specific population groups. A diagnosis of personality disorder can sustain long
      term diagnosis of MADD. 

PMID- 24917443
TI  - Antidepressant monotherapy and combination of antidepressants in the treatment of
      resistant depression in current clinical practice: A retrospective study.
AB  - Abstract Objectives. The aim of this study was to compare efficacy of
      antidepressant monotherapies and combinations of antidepressants in the treatment
      of resistant patients in current clinical practice. Methods. We reviewed chart
      documents of resistant depressive inpatients treated at least 4 weeks with a new
      treatment. Depressive symptoms and clinical status were assessed using Montgomery
      and Asberg Depression Rating Scale (MADRS), Beck Depression Inventory-Short Form
      and Clinical Global Impression at the baseline, week 2 and in the end of
      treatment. Results. We identified 81 patients (27 with combinations and 51 with
      monotherapies) that were suitable for analyses. The combination group achieved
      higher reduction of MADRS score (14.6 vs 10.2 pts., p=0.02) and response rate (>=
      50% reduction of MADRS, 67% vs 39%, p=0.03). Number needed to treat for response
      was 4. Conclusions. Based on our results, we suggest that combination of
      antidepressants might be more effective than monotherapy in clinical practice. 

PMID- 24917444
TI  - Bright light therapy: Minimizing light induced side effects with an innovative
      light setup.
AB  - Abstract Objective. Bright light therapy (BLT) is regarded to be an effective
      treatment against seasonal depression (SAD). Conventional BLT devices are
      reported to evoke few, but inconvenient symptoms. This study evaluated side
      effects associated with a new technology for BLT in a healthy population.
      Methods. In an uncontrolled study design 20 healthy Caucasians received 30 min
      light exposures on three consecutive mornings. Immediate side effects were
      evaluated using questionnaires. The new light cabin was equipped with fluorescent
      lamps (light colour 965 = 6,500 K, CRI >90) with a maximum illumination of 5,000
      lux and a maximum luminance of 1,500 cd/m(2). Occurrence of headache was
      determined to be the main objective. Results. Nineteen volunteers completed the
      study. No headache was reported at any time. With a prevalence of 21.1% blurring
      was observed to occur more often after light exposure. Conclusion. With the
      evaluated light cabin the most prominent short-term side effects of BLT can be
      minimized, enhancing patients' adherence. 

PMID- 24917445
TI  - The relationship between medicine, spirituality and religion: three models for
      integration.
AB  - The integration of medicine and religion is challenging for historical, ethical,
      practical and conceptual reasons. In order to make more explicit the bases and
      goals of relating spirituality and medicine, we distinguish here three
      complementary perspectives: a whole-person care model that emphasizes teamwork
      among generalists and spiritual professionals; an existential functioning view
      that identifies a role for the clinician in promoting full health, including
      spiritual well-being; and an open pluralism view, which highlights the importance
      of differing spiritual and cultural traditions in shaping the relationship. 

PMID- 24917446
TI  - Insulin-like factor 3 plasma levels in acromegaly before and after somatostatin
      analog treatment.

PMID- 24917447
TI  - The association of atopy with incidence of ischemic heart disease, stroke, and
      diabetes.
AB  - Allergy is a systemic inflammatory disease that could theoretically affect the
      risk of cardiovascular disease (CVD) and diabetes through inflammatory pathways
      or mast cell-induced coronary spasm. Whether allergy is associated with an
      increased risk of CVD and diabetes is largely unknown. We investigated the
      association between atopy as assessed by IgE sensitization, a well-accepted
      biomarker of allergy, and incidence of ischemic heart disease, stroke, and
      diabetes in five Danish population-based cohorts. A total of 14,849 participants
      were included in the study. Atopy was defined as serum-specific IgE positivity to
      inhalant allergens. The Danish National Diabetes Register enabled identification
      of incident diabetes. Likewise, the Danish Registry of Causes of Death and the
      Danish National Patient Register provided information on fatal and non-fatal
      ischemic heart disease and stroke. Data were analyzed by Cox regression analyses
      with age as underlying time axis and adjusted for study cohort, gender,
      education, body mass index, alcohol intake, smoking habits, physical activity
      during leisure time, serum lipids, and blood pressure. The prevalence of atopy
      was 26.9 % (n = 3,994). There were 1,170, 817, and 1,063 incident cases of
      ischemic heart disease, stroke, and diabetes, respectively (median follow-up 11.2
      years). The hazard ratios, HRs (95 % confidence intervals, CIs) for atopics
      versus non-atopics: for ischemic heart disease (HR 1.00, 95 % CI 0.86, 1.16),
      stroke (HR 1.18, 95 % CI 0.99, 1.41), and diabetes (HR 1.06, 95 % CI 0.91, 1.23).
      Our results did not support the hypothesis that atopy is associated with higher
      risk of ischemic heart disease, stroke, or diabetes. However, a small-moderately
      increased risk cannot be excluded from our data. 

PMID- 24917448
TI  - Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell
      type specific manner.
AB  - BACKGROUND: Epstein-Barr virus is a human herpesvirus that infects a majority of
      the human population. Primary infection of Epstein-Barr virus (EBV) causes the
      syndrome infectious mononucleosis. This virus is also associated with several
      cancers, including Burkitt's lymphoma, post-transplant lymphoproliferative
      disorder and nasopharyngeal carcinoma. As all herpesvirus family members, EBV
      initially replicates lytically to produce abundant virus particles, then enters a
      latent state to remain within the host indefinitely. METHODS: Through a genetic
      screen in Drosophila, we determined that reduction of Drosophila Tor activity
      altered EBV immediate-early protein function. To further investigate this
      finding, we inhibited mTOR in EBV-positive cells and investigated subsequent
      changes to lytic replication via Western blotting, flow cytometry, and
      quantitative PCR. The student T-test was used to evaluate significance. RESULTS:
      mTOR, the human homolog of Drosophila Tor, is an important protein at the center
      of a major signaling pathway that controls many aspects of cell biology. As the
      EBV immediate-early genes are responsible for EBV lytic replication, we examined
      the effect of inhibition of mTORC1 on EBV lytic replication in human EBV-positive
      cell lines. We determined that treatment of cells with rapamycin, which is an
      inhibitor of mTORC1 activity, led to a reduction in the ability of B cell lines
      to undergo lytic replication. In contrast, EBV-positive epithelial cell lines
      underwent higher levels of lytic replication when treated with rapamycin.
      CONCLUSIONS: Overall, the responses of EBV-positive cell lines vary when treated
      with mTOR inhibitors, and this may be important when considering such inhibitors
      as anti-cancer therapeutic agents.

PMID- 24917449
TI  - Conditioning out-of-date bank-stored red blood cells using a cell-saver auto
      transfusion device: effects on numbers of red cells and quality of suspension
      fluid.
AB  - We investigated the utility of a cell-saver device for processing out-of-date red
      blood cells, by washing twenty bags of red blood cells that had been stored for
      between 36 and 55 days. The volume of recovered cells, and the characteristics of
      the suspension fluid, were measured before and after treatment. The ratio of free
      haemoglobin to total haemoglobin was up to 0.02 before processing, and up to
      0.011 afterwards, changing by between -0.013 and +0.003. This ratio met the
      current standard for free haemoglobin (less than 0.008 in more than 75% of
      samples), both before and after processing. Ninety-three percent of red blood
      cells survived the process. Potassium ion concentration fell from above 15
      mmol.l(-1) in all cases, to a mean of 6.4 mmol.l(-1) (p < 0.001). The pH rose to
      a mean value of 6.44 (p = 0.001). Lactate ion concentration fell to a mean value
      of 14 mmol.l(-1) (p < 0.001). Sodium ion concentration rose from a mean value of
      93 mmol.l(-1) to a mean value of 140 mmol.l(-1) (p < 0.001). A useful proportion
      of out-of-date red blood cells remained intact after conditioning using a cell
      saver, and the process lowered concentrations of potentially toxic solutes in the
      fluid in which they were suspended. 

PMID- 24917450
TI  - Ventilator-integrated jet nebulization systems: tidal volume control and
      efficiency of synchronization.
AB  - BACKGROUND: Jet nebulizers constitute the aerosolization devices most frequently
      used during mechanical ventilation. Continuous nebulization can influence the
      delivered tidal volume (V(T)) and lead to significant medication loss during
      expiration. Ventilators thus provide integrated jet nebulization systems that are
      synchronized during inspiration and ostensibly keep VT constant. METHODS: This
      was a bench study of systems integrated in the Evita XL, Avea, Galileo, and G5
      ventilators. The VT delivered with and without nebulization, the inspiratory
      synchronization of nebulization, and the aerosol deposition were measured with 2
      locations of the nebulizer. RESULTS: Changes in V(T) with the nebulizer were
      below 20 mL and below 10% of set V(T) for all ventilators. Synchronization was
      good at the beginning of insufflation, but prolonged nebulization was observed
      with all ventilators at the end of insufflation, until up to 1 s during
      expiration: 5-80% of nebulization occurred during expiration with significant
      aerosol loss in the expiratory limb. Synchrony could be improved by (1) reducing
      gas compression/decompression phenomena proximal to the jet nebulizer and (2)
      increasing inspiratory time, which reduced the amount of nebulization occurring
      during expiration. Placing the nebulizer upstream in the inspiratory limb did not
      affect inspiratory synchrony but allowed reduction of the amount of aerosol lost
      in the expiratory limb. CONCLUSIONS: Jet nebulizer systems integrated in the
      tested ventilators are reliable in terms of V(T) control. Gas compression in
      tubing driving gas to the nebulizer delays synchronization and reduces
      nebulization yield if the nebulizer is placed close to the Y-piece. Increasing
      inspiratory time with no end-inspiratory pause reduces the expiratory loss of
      medication if placement of the nebulizer upstream in the inspiratory limb is not
      feasible.

PMID- 24917451
TI  - Sleep apnea risk in subjects with asthma with or without comorbid rhinitis.
AB  - BACKGROUND: As many as 80% of patients with asthma suffer from allergic rhinitis
      (AR), and rhinitis symptoms are associated with sleep complaints The aim of this
      cross-sectional study was to assess the prevalence of obstructive sleep apnea
      syndrome risk in patients with asthma and to explore the association between
      comorbid rhinitis and obstructive sleep apnea syndrome risk. METHODS: Subjects
      with asthma were recruited by general practitioners during a control visit.
      Physicians compiled a questionnaire that assessed the presence of AR according to
      ARIA (Allergic Rhinitis and Its Impact on Asthma) guidelines and factors
      influencing the risk of obstructive sleep apnea syndrome (gastroesophageal reflux
      disease, obesity, smoking). Subjects completed a questionnaire evaluating the
      presence and severity of AR and the STOP-BANG questionnaire (snoring, tiredness
      during daytime, observed apnea, high blood pressure, body mass index, age, neck
      circumference, gender), a validated screening method to identify obstructive
      sleep apnea syndrome risk. Physicians were blinded to the subjects'
      questionnaires, ensuring objectivity of the method. RESULTS: The analyses were
      conducted on 1,941 subjects (males 58%, mean age 48.2 +/- 15.2 y): 740 with
      asthma alone and 1,201 with asthma and AR. STOP-BANG revealed that 52.6% of the
      subjects were at increased risk of obstructive sleep apnea syndrome: 47.3% of
      subjects with asthma alone and 55.9% of patients with asthma and AR. Rhinitis was
      associated with a 1.44 times higher odds ratio for having obstructive sleep apnea
      syndrome risk. Rhinitis duration and severity were associated with obstructive
      sleep apnea syndrome risk, although the latter deserved greater importance. The
      results showed that, once a correction for each of these factors was performed,
      subjects with AR with an odds ratio of 1.99 were reported to be at risk of
      obstructive sleep apnea syndrome. CONCLUSIONS: The probable increased risk of
      obstructive sleep apnea syndrome is associated with the concomitant presence of
      rhinitis, independent of obesity and other contributors to risk of obstructive
      sleep apnea syndrome.

PMID- 24917452
TI  - Clinical use of the volume-time curve for endotracheal tube cuff management.
AB  - BACKGROUND: Previous investigation showed that the volume-time curve technique
      could be an alternative for endotracheal tube (ETT) cuff management. However, the
      clinical impact of the volume-time curve application has not been documented. The
      purpose of this study was to compare the occurrence and intensity of a sore
      throat, cough, thoracic pain, and pulmonary function between these 2 techniques
      for ETT cuff management: volume-time curve technique versus minimal occlusive
      volume (MOV) technique after coronary artery bypass grafting. METHODS: A total of
      450 subjects were randomized into 2 groups for cuff management after intubation:
      MOV group (n = 222) and volume-time curve group (n = 228). We measured cuff
      pressure before extubation. We performed spirometry 24 h before and after
      surgery. We graded sore throat and cough according to a 4-point scale at 1, 24,
      72, and 120 h after extubation and assessed thoracic pain at 24 h after
      extubation and quantified the level of pain by a 10-point scale. RESULTS: The
      volume-time curve group presented significantly lower cuff pressure (30.9 +/- 2.8
      vs 37.7 +/- 3.4 cm H2O), less incidence and intensity of sore throat (1 h, 23.7
      vs 51.4%; and 24 h, 18.9 vs 40.5%, P < .001), cough (1 h, 19.3 vs 48.6%; and 24
      h, 18.4 vs 42.3%, P < .001), thoracic pain (5.2 +/- 1.8 vs 7.1 +/- 1.7), better
      preservation of FVC (49.5 +/- 9.9 vs 41.8 +/- 12.9%, P = .005), and FEV1 (46.6 +/
      1.8 vs 38.6 +/- 1.4%, P = .005) compared with the MOV group. CONCLUSIONS: The
      subjects who received the volume-time curve technique for ETT cuff management
      presented a significantly lower incidence and severity of sore throat and cough,
      less thoracic pain, and minimally impaired pulmonary function than those subjects
      who received the MOV technique during the first 24 h after coronary artery bypass
      grafting.

PMID- 24917453
TI  - Pulmonary rehabilitation improves subjective sleep quality in COPD.
AB  - BACKGROUND: Poor sleep quality is often reported among patients with COPD.
      Pulmonary rehabilitation (PR) is beneficial in improving exercise capacity and
      health-related quality of life (HRQOL). However, its benefit in terms of sleep
      quality in patients with COPD remains unclear. This study aimed to investigate
      the effects of PR on sleep quality of patients with COPD. METHODS: Thirty-four
      subjects with COPD were studied. All subjects participated in a 12-week (2
      sessions/week) hospital-based out-patient PR study. Baseline and post-PR status
      were evaluated by spirometry, a sleep questionnaire (Pittsburgh Sleep Quality
      Index [PSQI]), a disease-specific questionnaire of HRQOL (St George Respiratory
      Questionnaire [SGRQ]), cardiopulmonary exercise testing, respiratory muscle
      strength, and the Borg dyspnea scale. RESULTS: Mean FEV1/FVC in the subjects was
      0.49 +/- 0.13, and the mean FEV1 was 1.06 +/- 0.49 L/min (49.7 +/- 18.0% of
      predicted). After PR, the PSQI score decreased from 9.41 +/- 4.33 to 7.82 +/-
      3.90 (P < .001). The number of subjects with a PSQI score > 5 also decreased
      (85.3-64.7%, P = .006). There were significant improvements in HRQOL (SGRQ, P =
      .003), exercise capacity (peak oxygen uptake, P < .001; and work rate, P < .001),
      dyspnea score (P < .001), and respiratory muscle strength (inspiratory muscle
      strength, P = .005; and expiratory muscle strength, P = .004) after PR. There
      were no significant changes in pulmonary function test results (FEV1, P = .77;
      FVC, P = .90; FEV1/FVC, P = .90). CONCLUSIONS: PR results in significant
      improvement in sleep quality, along with concurrent improvements in HRQOL and
      exercise capacity. PR is an effective nonpharmacologic treatment to improve sleep
      quality in patients with COPD and should be part of their clinical management.

PMID- 24917454
TI  - Intermittent aerosol delivery to the lungs during high-flow nasal cannula
      therapy.
AB  - INTRODUCTION: Use of submicrometer particles combined with condensational growth
      techniques has been proposed to reduce drug losses within components of high-flow
      nasal cannula therapy systems and to enhance the dose reaching the lower
      respiratory tract. These methods have been evaluated using continuous inhalation
      flow rather than realistic inhalation/exhalation breathing cycles. The goal of
      this study was to evaluate in vitro aerosol drug delivery using condensational
      growth techniques during high-flow nasal cannula therapy using realistic
      breathing profiles and incorporating intermittent aerosol delivery techniques.
      METHODS: A mixer-heater combined with a vibrating mesh nebulizer was used to
      generate a submicrometer aerosol using a formulation of 0.2% albuterol sulfate
      and 0.2% sodium chloride in water. Delivery efficiency of the aerosol for 1 min
      through a nasal cannula was considered using an intermittent delivery regime with
      aerosol being emitted for either the entire inhalation time (2 s) or half of the
      inhalation period (1 s) and compared with continuous delivery. The deposition of
      the aerosol was evaluated in the nasal delivery components (ventilator tubing and
      cannula) and an in vitro adult nose-mouth-throat (NMT) model using 3 realistic
      breathing profiles. RESULTS: Significant improvements in dose delivered to the
      exit of the NMT model (ex-NMT) were observed for both condensational growth
      methods using intermittent aerosol delivery compared with continuous delivery,
      and increasing the tidal volume was found useful. The combination of the largest
      tidal volume with the shortest intermittent delivery time resulted in the lowest
      respiration losses and the highest ex-NMT delivered dose. CONCLUSIONS:
      Intermittent aerosol delivery using realistic breathing profiles of submicrometer
      condensational growth aerosols was found to be efficient in delivering nasally
      administered drugs in an in vitro airway model.

PMID- 24917455
TI  - Persistence of mucosal T-cell responses to herpes simplex virus type 2 in the
      female genital tract.
AB  - Relatively little is known about the human T-cell response to herpes simplex
      virus type 2 (HSV-2) in the female genital tract, a major site of heterosexual
      HSV-2 acquisition, transmission, and reactivation. In order to understand the
      role of local mucosal immunity in HSV-2 infection, T-cell lines were expanded
      from serial cervical cytobrush samples from 30 HSV-2-infected women and examined
      for reactivity to HSV-2. Approximately 3% of the CD3+ T cells isolated from the
      cervix were HSV-2 specific and of these, a median of 91.3% were CD4+, whereas a
      median of 3.9% were CD8+. HSV-2-specific CD4+ T cells expanded from the cervix
      were not only more frequent than CD8+ T cells but also exhibited greater breadth
      in terms of antigenic reactivity. T cells directed at the same HSV-2 protein were
      often detected in serial cervical cytobrush samples and in blood. Thus, broad and
      persistent mucosal T-cell responses to HSV-2 were detected in the female genital
      tract of HSV-2+ women suggesting that these cells are resident at the site of HSV
      2 infection. Understanding the role of these T cells at this biologically
      relevant site will be central to the elucidation of adaptive immune mechanisms
      involved in controlling HSV-2 disease. 

PMID- 24917456
TI  - A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.
AB  - Lymphocyte recruitment to peripheral tissues is fundamental for immune
      surveillance and homeostasis, but the chemokines and chemokine receptors
      responsible for tissue-specific homing of T cells to the upper airway mucosa have
      not been determined. To address this, we analyzed the chemokines expressed in the
      normal human nasal mucosa and found that CCL28 is preferentially expressed at a
      high level on the lumenal face of vascular endothelial cells in the mucosa.
      Analysis of the cognate chemokine receptors revealed that close to 50% of the
      CD4(+) T cells in the human nasal mucosa expressed the CCL28 receptor CCR3,
      whereas CCR3 was hardly detectable on T cells in the small intestine and skin. In
      the circulation, CCR3(+) T cells comprised a small subset that did not express
      homing receptors to the intestine or skin. Moreover, depletion of CCR3(+)CD4(+) T
      cells abrogated the proliferative response of human blood CD4(+) T cells against
      the opportunistic nasopharyngeal pathogen Haemophilus influenzae, indicating that
      the CCR3(+)CD4(+) T-cell subset in the circulation contains antigen specificities
      relevant for the upper airways. Together, these findings indicate that CCL28-CCR3
      interactions are involved in the homeostatic trafficking of CD4(+) T cells to the
      upper airways. 

PMID- 24917458
TI  - Novel validated spectrofluorimetric methods for the determination of taurine in
      energy drinks and human urine.
AB  - Two sensitive, selective, economic and validated spectrofluorimetric methods were
      developed for the determination of taurine in energy drinks and spiked human
      urine. Method Iota is based on fluorimetric determination of the amino acid
      through its reaction with Hantzsch reagent to form a highly fluorescent product
      measured at 490 nm after excitation at 419 nm. Method IotaIota is based on the
      reaction of taurine with tetracyanoethylene yielding a fluorescent charge
      transfer complex, which was measured at lambdaex /em of (360 nm/450 nm). The
      proposed methods were subjected to detailed validation procedures, and were
      statistically compared with the reference method, where the results obtained were
      in good agreement. Method Iota was further applied to determine taurine in energy
      drinks and spiked human urine giving promising results. Moreover, the
      stoichiometry of the reactions was studied, and reaction mechanisms were
      postulated.

PMID- 24917457
TI  - Short-chain fatty acids induce both effector and regulatory T cells by
      suppression of histone deacetylases and regulation of the mTOR-S6K pathway.
AB  - Microbial metabolites, such as short-chain fatty acids (SCFAs), are highly
      produced in the intestine and potentially regulate the immune system. We studied
      the function of SCFAs in the regulation of T-cell differentiation into effector
      and regulatory T cells. We report that SCFAs can directly promote T-cell
      differentiation into T cells producing interleukin-17 (IL-17), interferon-gamma,
      and/or IL-10 depending on cytokine milieu. This effect of SCFAs on T cells is
      independent of GPR41 or GPR43, but dependent on direct histone deacetylase (HDAC)
      inhibitor activity. Inhibition of HDACs in T cells by SCFAs increased the
      acetylation of p70 S6 kinase and phosphorylation rS6, regulating the mTOR pathway
      required for generation of Th17 (T helper type 17), Th1, and IL-10(+) T cells.
      Acetate (C2) administration enhanced the induction of Th1 and Th17 cells during
      Citrobacter rodentium infection, but decreased anti-CD3-induced inflammation in
      an IL-10-dependent manner. Our results indicate that SCFAs promote T-cell
      differentiation into both effector and regulatory T cells to promote either
      immunity or immune tolerance depending on immunological milieu. 

PMID- 24917459
TI  - Quantified sex: a critical analysis of sexual and reproductive self-tracking
      using apps.
AB  - Digital health technologies are playing an increasingly important role in
      healthcare, health education and voluntary self-surveillance, self-quantification
      and self-care practices. This paper presents a critical analysis of one digital
      health device: computer apps used to self-track features of users' sexual and
      reproductive activities and functions. After a review of the content of such apps
      available in the Apple App Store and Google PlayTM store, some of their
      sociocultural, ethical and political implications are discussed. These include
      the role played by these apps in participatory surveillance, their configuration
      of sexuality and reproduction, the valorising of the quantification of the body
      in the context of neoliberalism and self-responsibility, and issues concerning
      privacy, data security and the use of the data collected by these apps. It is
      suggested that such apps represent sexuality and reproduction in certain defined
      and limited ways that work to perpetuate normative stereotypes and assumptions
      about women and men as sexual and reproductive subjects. Furthermore there are
      significant ethical and privacy implications emerging from the use of these apps
      and the data they produce. The paper ends with suggestions concerning the
      'queering' of such technologies in response to these issues.

PMID- 24917460
TI  - PKCdelta phosphorylation is an upstream event of GSK3 inactivation-mediated ROS
      generation in TGF-beta1-induced senescence.
AB  - Transforming growth factor beta1 (TGF-beta1) induces Mv1Lu cell senescence
      through inactivating glycogen synthase kinase 3 (GSK3), thereby inactivating
      complex IV and increasing intracellular ROS. In the present study, we identified
      protein kinase C delta (PKCdelta) as an upstream regulator of GSK3 inactivation
      in this mechanism of TGF-beta1-induced senescence. When Mv1Lu cells were exposed
      to TGF-beta1, PKCdelta phosphorylation simultaneously increased with GSK3
      phosphorylation, and then AKT and ERK were phosphorylated. AKT phosphorylation
      and Smad signaling were independent of GSK3 phosphorylation, but ERK
      phosphorylation was downstream of GSK3 inactivation. TGF-beta1-triggered GSK3
      phosphorylation was blocked by inhibition of PKCdelta, using its pharmacological
      inhibitor, Rottlerin, or overexpression of a dominant negative PKCdelta mutant,
      but GSK3 inhibition with SB415286 did not alter PKCdelta phosphorylation.
      Activation of PKCdelta by PMA delayed cell growth and increased intracellular ROS
      level, but did not induce senescent phenotypes. In addition, overexpression of
      wild type or a constitutively active PKCdelta mutant was enough to delay cell
      growth and decrease the mitochondrial oxygen consumption rate and complex IV
      activity, but weakly induce senescence. However, PMA treatment on Mv1Lu cells,
      which overexpress wild type and constitutively active PKCdelta mutants,
      effectively induced senescence. These results indicate that PKCdelta plays a key
      role in TGF-beta1-induced senescence of Mv1Lu cells through the phosphorylation
      of GSK3, thereby triggering mitochondrial complex IV dysfunction and
      intracellular ROS generation.

PMID- 24917461
TI  - A simple model of cortical culture growth: burst property dependence on network
      composition and activity.
AB  - This paper describes large-scale simulations of growth, network formation, and
      behavior in cultures of dissociated cortical cells. A neuron model that
      incorporates synaptic facilitation/depression and neurite outgrowth/retraction
      was used to construct virtual cultures of 10,000 cells whose spiking behavior and
      evolution were investigated in closed-loop simulations. This approach allows us
      to perform detailed analysis of the effects of model parameters on burst shape
      and timing, their changes, and the interrelationship among these behaviors, gross
      network structure, and model parameters. We examined the effects of two
      parameters--network composition (fraction of excitatory cells) and neuron
      excitability (activity level corresponding to neurite outgrowth equilibrium)--on
      network structure and behavior. Our results suggest that much of the burst shape
      and timing observed in vitro can be explained by a model that includes only
      closed-loop neurite outgrowth and dynamic synapses; features such as LTP/LTD,
      random connectivity, long-distance connections, and detailed neurite topology are
      not necessary.

PMID- 24917462
TI  - Treatment of proximal humeral fractures with reverse shoulder arthroplasty in
      elderly patients.
AB  - BACKGROUND: Proximal humeral fractures in four or even only three parts, with
      metaphyseal hinge distances of <8 mm, represent a serious and widely debated
      problem. Reduction is complex and plating is often instable, especially in
      elderly patients. Failures, sometimes involving necrosis of the head, are
      frequent. Hemiarthroplasty has long been used for 3- or 4-part complex fractures,
      even in young patients, although often with sub-optimal results, due to
      reabsorption of tuberosities. This complication has partly been overcome with
      reverse shoulder prostheses which, although more invasive than partial ones, may
      lead to less disappointing results, even in cases of reabsorption of
      tuberosities. We have data on a homogeneous series of patients treated with
      reverse shoulder arthroplasty for proximal fractures, with a maximum follow-up of
      10 years. The aim of this study was mainly to identify which cases can be
      selected for effective treatment and which technical aspects are best to adopt.
      MATERIALS AND METHODS: There were 33 patients in this study, mean age 76.6 years
      (range 54-85). Fractures were classified according to Neer. Surgery was
      undertaken on average 4.4 days after trauma. The deltopectoral approach was used.
      Sutures were hooked over the major and lesser tubercles for later reduction and
      fixation after the prosthesis had been applied. This passage was sometimes not
      possible in cases of serious degeneration of the rotator cuff. One day after
      surgery, a shoulder brace providing an abducted angle of 15 degrees  was applied
      for 30 days. Patients were re-assessed with DASH and Constant scores (CS), and
      the ratio between healthy and operated shoulders was calculated. Physical
      examination was followed by X-rays, mainly to evaluate and classify any
      infraglenoid scapular notching according to Nerot. RESULTS: Mean follow-up was
      42.3 months (range 10-121). According to the CS, mean pain was 12.6/15 (range 3
      15/15), activities of daily living 16.3/20 (range 8-20/20), ROM 21.8 (range 8
      32/40) and power 5.4/25 (range 2-12/25). Total mean CS was 56.4 (range 23
      80/100). The mean DASH score was 49.7 (range 32-90). The ratio of the CS
      parameters between opposite and operated shoulders was on average 72.8 % (range
      28-90 %). Long-term complications were eight cases of scapular notching (24.2 %)
      of which four of grade 2 (12.1 %) and four of grade 1 (12.1 %). CONCLUSIONS:
      Total reverse prostheses are more invasive because they also compromise the
      glenoid surface of the scapula, but they do offer good stability, even in cases
      of damage to the rotator cuff. Reverse prostheses have great advantages as
      regards to ROM, allowing functional recovery, which is good in cases with re
      insertion of tuberosities, and acceptable in cases when tuberosities are not re
      inserted or resorbed. In our cases, the first 3 reverse prostheses lasted 10, 8.3
      and 7.3 years, and we believe that they will become increasingly long-lived, so
      that applying them in cases of complex fractures becomes more feasible. We prefer
      the deltopectoral approach because it can reduce and stabilize possible intra
      operative diaphyseal fractures. Possible scapular notching must be foreseen when
      inserting the glenosphere. We had eight cases (24.2 %), of which four were Nerot
      grade 1 and four were grade 2. Applying the Kirschner wire in an infero-anterior
      position allows the glenosphere to be lowered with a tilt of 10 degrees . Reverse
      prostheses are suitable for 3- or 4-part complex proximal humeral fractures in
      patients over 65. Prolonged physiokinesitherapy is essential.

PMID- 24917463
TI  - MicroRNA expression signatures for the prediction of BRCA1/2 mutation-associated
      hereditary breast cancer in paraffin-embedded formalin-fixed breast tumors.
AB  - Screening for germline mutations in breast cancer-associated genes BRCA1 and
      BRCA2 is indicated for patients with breast cancer from high-risk breast cancer
      families and influences both treatment options and clinical management. However,
      only 25% of selected patients test positive for BRCA1/2 mutation, indicating that
      additional diagnostic biomarkers are necessary. We analyzed 124 formalin-fixed
      paraffin-embedded (FFPE) tumor samples from patients with hereditary (104) and
      sporadic (20) invasive breast cancer, divided into two series (A and B).
      Microarray expression profiling of 829 human miRNAs was performed on 76 samples
      (Series A), and bioinformatics tool Prophet was used to develop and test a
      microarray classifier. Samples were stratified into a training set (n = 38) for
      microarray classifier generation and a test set (n = 38) for signature
      validation. A 35-miRNA microarray classifier was generated for the prediction of
      BRCA1/2 mutation status with a reported 95% (95% CI = 0.88-1.0) and 92% (95% CI:
      0.84-1.0) accuracy in the training and the test set, respectively. Differential
      expression of 12 miRNAs between BRCA1/2 mutation carriers versus noncarriers was
      validated by qPCR in an independent tumor series B (n = 48). Logistic regression
      model based on the expression of six miRNAs (miR-142-3p, miR-505*, miR-1248, miR
      181a-2*, miR-25* and miR-340*) discriminated between tumors from BRCA1/2 mutation
      carriers and noncarriers with 92% (95% CI: 0.84-0.99) accuracy. In conclusion, we
      identified miRNA expression signatures predictive of BRCA1/2 mutation status in
      routinely available FFPE breast tumor samples, which may be useful to complement
      current patient selection criteria for gene testing by identifying individuals
      with high likelihood of being BRCA1/2 mutation carriers. 

PMID- 24917464
TI  - Determination and pharmacokinetics of linarin in rat plasma after intramuscular
      administration of linarin solution and Yejuhua injection by HPLC.
AB  - A simple and sensitive HPLC method was developed and validated for the
      determination of linarin in rat plasma. Plasma samples were carried out by
      protein precipitation with acetonitrile and separated on a Shim-pack VP-ODS
      analytical column (250 * 4.6 mm, 5 um). The calibration curve was linear in the
      measured range of 20.8-4160 ng/mL and the lower limit of quantification was 20.8
      ng/mL for linarin. The validated method was successfully applied to the
      pharmacokinetic study of linarin in rat plasma after intramuscular administration
      of monomeric compound and traditional Chinese medicinal preparation - Yejuhua
      injection.

PMID- 24917465
TI  - New insights into the dynamics of vacuum impregnation of plant tissues and its
      metabolic consequences.
AB  - The complex and highly interconnected intercellular air spaces of plant tissues
      occupied by gas or native liquid has offered the possibility for impregnation
      with a wide range of compounds. In food processing, the development of vacuum
      impregnation has allowed a controlled way to introduce these compounds to the
      tissue structure aiming at modifying structural, nutritional, and/or functional
      properties as well as improving the processability of fruits and vegetables. In
      the last 10 years, more than 100 research articles have been published on the
      topic and significant insights had been gained including improved understanding
      of mechanisms for mass transfer as well as the development of new, fascinating
      industrial applications. In the recent years, our knowledge on these aspects has
      increased by bringing new exploration technologies for studying the impregnation
      of porous materials and plant cell physiology approaches to bear on the topic.
      The aim of this paper is to highlight some of these exciting advances.

PMID- 24917466
TI  - Eleutheroside E ameliorates arthritis severity in collagen-induced arthritis mice
      model by suppressing inflammatory cytokine release.
AB  - Rheumatoid arthritis is the most common arthritis and is mainly characterized by
      symmetric polyarticular joint disorders. Eleutheroside E (EE), a principal active
      constituent of Acanthopanax senticosus, is reported to have anti-inflammatory
      effect by inhibiting NF-kappaB activities. However, the effects of EE on
      rheumatoid arthritis (RA) severity are largely unknown. The purpose of this study
      was to indicate whether EE could ameliorate arthritis and reduce inflammatory
      cytokine release in collagen-induced arthritis (CIA) mice. The results showed
      that EE attenuated the severity of arthritis by reducing the mean arthritis score
      and arthritis incidence. EE also significantly decreased the inflammatory cell
      infiltration, pannus formation, cartilage damage, and bone erosion of CIA mice.
      Furthermore, EE caused a marked decrease of the production of TNF-alpha and IL-6
      in vivo and in vitro. These observations identify a novel function of EE that
      results in inhibition of cytokine release, highlighting EE was a potential
      therapeutic agent for RA. 

PMID- 24917467
TI  - Targeting dormant tuberculosis bacilli: results for molecules with a novel
      pyrimidone scaffold.
AB  - Our inability to completely control TB has been due in part to the presence of
      dormant mycobacteria. This also renders drug regimens ineffective and is the
      prime cause of the appearance of drug-resistant strains. In continuation of our
      efforts to develop novel antitubercular agents that especially target dormant
      mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were
      designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and
      subsequently tested against both the dormant and virulent BCG strain of M.
      tuberculosis. Some novel compounds have been identified which selectively inhibit
      the dormant tuberculosis bacilli with significantly low IC50 values. This study
      reports the second molecule after TMC-207, having the ability to inhibit
      tuberculosis bacilli exclusively in its dormant phase. The synthesis was
      accomplished by a modified multicomponent Biginelli reaction. A classification
      model was generated using the binary QSAR approach--recursive partitioning (RP)
      to identify structural characteristics related to the activity. Physicochemical,
      structural, topological, connectivity indices, and E-state key descriptors were
      used for generation of the decision tree. The decision tree could provide
      insights into structure-activity relationships that will guide the design of more
      potent inhibitors.

PMID- 24917472
TI  - Large cell acanthoma: a variant of solar lentigo with cellular hypertrophy.
AB  - BACKGROUND: Large cell acanthoma (LCA) is an epidermal proliferation of enlarged
      keratinocytes. There is a lack of consensus on whether it represents a unique
      neoplasm or not. To determine whether it is a variant of solar lentigo, we
      compared macroscopic, microscopic and immunophenotypic attributes of LCA with
      conventional solar lentigo, seborrheic keratosis, actinic keratosis and Bowen
      disease. METHODS: We constructed tissue microarrays containing multiple cores of
      LCA, solar lentigo, seborrheic keratosis, actinic keratosis and Bowen disease.
      Tissue microarray sections were blindly analyzed for microscopic morphologic
      variables. Corresponding ex vivo dermoscopic images from the original cases were
      blindly analyzed for macroscopic morphologic variables. Immunostained sections
      from the tissue microarray were tested for keratin 10, keratin 5/6, Bcl-2 and Ki
      67 expression by image analysis. RESULTS: There were no significant differences
      in the studied morphologic attributes between LCA and solar lentigo. All other
      tumor classes showed at least one significant morphologic difference with LCA.
      LCA and solar lentigo showed different keratin 10 and Bcl-2 signal intensities.
      CONCLUSIONS: LCA is best considered a variant of solar lentigo with cellular
      hypertrophy. The differences in immunophenotype and cell size could be because of
      differences in cell kinetics.

PMID- 24917473
TI  - Ground reaction force estimation using an insole-type pressure mat and joint
      kinematics during walking.
AB  - Kinetic analysis of walking requires joint kinematics and ground reaction force
      (GRF) measurement, which are typically obtained from a force plate. GRF is
      difficult to measure in certain cases such as slope walking, stair climbing, and
      track running. Nevertheless, estimating GRF continues to be of great interest for
      simulating human walking. The purpose of the study was to develop reaction force
      models placed on the sole of the foot to estimate full GRF when only joint
      kinematics are provided (Type-I), and to estimate ground contact shear forces
      when both joint kinematics and foot pressure are provided (Type-II and Type-II
      val). The GRF estimation models were attached to a commercial full body skeletal
      model using the AnyBody Modeling System, which has an inverse dynamics-based
      optimization solver. The anterior-posterior shear force and medial-lateral shear
      force could be estimated with approximate accuracies of 6% BW and 2% BW in all
      three methods, respectively. Vertical force could be estimated in the Type-I
      model with an accuracy of 13.75% BW. The accuracy of the force estimation was the
      highest during the mid-single-stance period with an average RMS for errors of
      3.10% BW, 1.48% BW, and 7.48% BW for anterior-posterior force, medial-lateral
      force, and vertical force, respectively. The proposed GRF estimation models could
      predict full and partial GRF with high accuracy. The design of the contact
      elements of the proposed model should make it applicable to various activities
      where installation of a force measurement system is difficult, including track
      running and treadmill walking. 

PMID- 24917474
TI  - Isolation of a neutral boron-containing radical stabilized by a cyclic
      (alkyl)(amino)carbene.
AB  - Utilizing a cyclic (alkyl)(amino)carbene (CAAC) as a ligand, neutral CAAC
      stabilized radicals containing a boryl functionality could be prepared by
      reduction of the corresponding haloborane adducts. The radical species with a
      duryl substituent was fully characterized by single-crystal X-ray structural
      analysis, EPR spectroscopy, and DFT calculations. Compared to known neutral boryl
      radicals, the isolated radical species showed larger spin density on the boron
      atom. Furthermore, the compound that was isolated is extraordinarily stable to
      high temperatures under inert conditions, both in solution and in the solid
      state. Electrochemical investigations of the radical suggest the possibility to
      generate a stable formal boryl anion species. 

PMID- 24917475
TI  - Rational selection of alternative, environmentally compatible surfactants for
      biotechnological production of pharmaceuticals--a step toward green
      biotechnology.
AB  - The biotechnological production of pharmaceutical active substances needs
      ancillary substances. Surfactants are used at the end of the cell culture as a
      protection against potential viral or bacterial contamination and to lyse the
      producing cells for isolation and purification of the products. To find a
      replacement for a surfactant that had raised environmental concern,
      environmentally relevant data for potential alternatives were searched for in the
      literature. Significant data gaps were filled with additional tests:
      biodegradability, algal growth inhibition, acute daphnid immobilization and
      chronic daphnid reproduction toxicity, acute fish toxicity, and activated sludge
      respiration inhibition. The results were used to model removal in the wastewater
      treatment plants (WWTPs) serving 3 biotechnological production sites in the Roche
      Group. Predicted environmental concentrations (PECs) were calculated using
      realistic amounts of surfactants and site-specific wastewater fluxes, modeled
      removals for the WWTPs and dilution factors by the respective receiving waters.
      Predicted no-effect concentrations (PNECs) were derived for WWTPs and for both
      fresh and marine receiving waters as the treated wastewater of 1 production site
      is discharged into a coastal water. This resulted in a spreadsheet showing PECs,
      PNECs, and PEC / PNEC risk characterization ratios for the WWTPs and receiving
      waters for all investigated surfactants and all 3 sites. This spreadsheet now
      serves as a selection support for the biotechnological developers. This risk
      based prioritization of surfactants is a step toward green biotechnological
      production.

PMID- 24917476
TI  - Iron(III) bound by hydrosulfide anion ligands: NO-promoted stabilization of the
      [Fe(III)-SH] motif.
AB  - Spontaneous transformation of the thermally stable [HS](-)-bound {Fe(NO)2}(9)
      dinitrosyl iron complex (DNIC) [(HS)2Fe(NO)2](-) (1) into [(NO)2Fe(MU-S)]2(2-)
      (Roussin's red salt (RRS)) along with release of H2S, probed by NBD-SCN (NBD =
      nitrobenzofurazan), was observed when DNIC 1 was dissolved in water at ambient
      temperature. The reversible transformation of RRS into DNIC 1 (RRS -> DNIC 1) in
      the presence of H2S was demonstrated. In contrast, the thermally unstable
      hydrosulfide-containing mononitrosyl iron complex (MNIC) [(HS)3Fe(III)(NO)](-)
      (3) and [Fe(III)(SH)4](-) (5) in THF/DMF spontaneously dimerized into the first
      structurally characterized Fe(III)-hydrosulfide complexes [(NO)(SH)Fe(MU-S)]2(2-)
      (4) with two {Fe(NO)}(7) motifs antiferromagnetically coupled and [(SH)2Fe(MU
      S)]2(2-) (6) resulting from two Fe(III) (S = 5/2) centers antiferromagnetically
      coupled to yield an S = 0 ground state with thermal occupancy of higher spin
      states, respectively. That is, the greater the number of NO ligands bound to
      [2Fe2S], the larger the antiferromagnetic coupling constant. On the basis of DFT
      computation and the experimental (and calculated) reduction potential (E1/2) of
      complexes 1, 3, and 5, the NO-coordinate ligand(s) of complexes 1 and 3 serves as
      the stronger electron-donating ligand, compared to thiolate, to reduce the
      effective nuclear charge (Zeff) of the iron center and prevent DNIC 1 from
      dimerization in an organic solvent (MeCN). 

PMID- 24917477
TI  - Economic evaluations in bipolar disorder: a systematic review and critical
      appraisal.
AB  - BACKGROUND: Bipolar disorder (BD) is a chronic illness and is one of the
      worldwide leading causes of disability. It is often a lifelong illness and incurs
      a substantial economic burden on the health care system, the patients, and
      society as a whole. However, there are few studies evaluating the economic impact
      of alternative strategies in the management of BD. OBJECTIVES: We reviewed and
      critically appraised the available published economic evidence on BD management.
      In addition, we explored advantages and disadvantages of different methods used
      in the economic evaluation of the management of BD. METHODS: A systematic
      literature search was undertaken using seven electronic databases to identify all
      English language articles published between January 1980 and March 2012 that
      provided data on complete economic evaluations for any treatment strategy for BD.
      The quality of included studies was appraised according to recommendations from
      the Cochrane Collaboration. RESULTS: A total of 7,284 citations were obtained.
      After initial screening, 20 eligible studies were identified, five of which were
      trial-based, and 15 of which were model-based economic evaluations. Given the
      variability in methods and the quality of the identified studies, no conclusive
      recommendation for the most cost-effective therapy for BD could be provided.
      CONCLUSIONS: The cost-effectiveness of different treatment strategies varied
      between settings, and transferability of these results across settings remains
      questionable. Although additional research using a longer time horizon is
      required to validate the findings for trial-based economic evaluations, discrete
      event simulation appears to be the most natural and plausible technique for
      modeling the cost-effectiveness of alternative BD treatment strategies.

PMID- 24917478
TI  - The relationship between laminoplasty opening angle and increased sagittal canal
      diameter and the prediction of spinal canal expansion following double-door
      cervical laminoplasty.
AB  - PURPOSE: To clarify the relationship between laminoplasty opening angle (LOA) and
      the increase in sagittal canal diameter (SCD) in double-door cervical
      laminoplasty (DDCL) and to predict the increase in SCD using the resulting
      formula. METHODS: We analyzed 20 patients with multilevel cervical spondylotic
      myelopathy who underwent DDCL between September 2010 and January 2013. The pre-
      and post-operative parameters of the cervical spinal canal were measured by
      computed tomography. We deduced a formula describing the relationship between LOA
      and the increase in SCD and used it to predict the increase in SCD of these
      patients as LOA increased. RESULTS: When the C3-C7 LOA was 25 degrees -45 degrees
      , the magnitude of the increase in SCD was notable (increases of 3.08-5.6 mm
      compared with the pre-operative SCD). When the C3-C7 LOA was more than 45 degrees
      , the magnitude of the increase in SCD was relatively smaller; the increase in C3
      C7 SCD with a 55 degrees  LOA was merely 0.4 mm more than with a 45 degrees  LOA.
      When LOA was 30 degrees  at C3-C6 or 40 degrees  at C7, the increase in SCD was
      more than 4 mm. When the C3-C6 LOA was 40 degrees , SCD increased by more than 5
      mm. CONCLUSIONS: The formula accurately showed the relationship between LOA and
      the increase in SCD in DDCL. Based on the LOA, increases in SCD following C3-C7
      laminoplasty can be accurately predicted using this formula. This enables DDCL
      based on accurate individual LOAs, which prevents inadequate or excessive
      opening.

PMID- 24917479
TI  - Lumbo-pelvic related indexes: impact on adult spinal deformity surgery.
AB  - PURPOSE: Lumbo-pelvic indexes appeared recently in the literature taking
      advantage from the relationship between pelvic incidence (PI) and lumbar lordosis
      (LL). Schwab proposed to subtract LL from PI (PI-LL) as Boissiere proposed the
      lumbar lordosis index (LLI), which is the ratio between LL and PI (LL/PI). Both
      indexes have been described to weight LL by a constant parameter not affected by
      degenerative processes, the PI. The aim of this study is to evaluate these
      parameters in adult spinal deformity (ASD) by analyzing their relationship with
      spinal malalignment and vertebral osteotomies. METHODS: Two groups of patients
      with an ASD were realized; an adult scoliosis group (n = 78) and a postoperative
      flat-back syndrome group (n = 20). In the adult scoliosis group, 28 patients
      underwent an osteotomy [pedicle subtraction osteotomy (PSO) or Smith Petersen
      osteotomy] and 50 patients were corrected by posterior fusion without osteotomy.
      In the postoperative flat-back syndrome group all patients underwent a PSO. All
      patients had preoperative and postoperative full spine EOS radiographies to
      measure spino-pelvic parameters. The lack of lordosis was calculated, after
      prediction of theoretical LL from Legaye's formula, by subtracting measured LL to
      theoretical LL. Correlation analysis between the different parameters was
      performed. RESULTS: Both lumbo-pelvic parameters highly correlated with spinal
      malalignment (r = 0.97 for PI-LL and r = -0.97 for LLI for total patients) and
      were highly predictive of a spinal osteotomy performance (r = 0.88 for PI-LL >28
      degrees  and r = 0.94 for LLI <0.5). Sagittal vertical axis (r = 0.67) and pelvic
      tilt (r = 0.64) correlated moderately with spinal malalignment for total
      patients. The LLI was more correlated with spinal osteotomies in the adult
      scoliosis group (r = 0.86 for PI-LL >28 degrees  and r = 0.94 for LLI <0.5), as
      Schwab's index was more precise to predict osteotomies in the postoperative flat
      back syndrome group (Youden index = 0.95 for PI-LL >28 degrees  vs 0.90 for LLI
      <0.5). CONCLUSIONS: This study highlights the necessity to considerer spinal
      malalignment with lumbo-pelvic indexes as they appear to be highly correlated
      with lack of LL. They can be used as mathematical tools to detect spinal
      malalignment in ASD and guide the surgeon's decision of realizing a vertebral
      osteotomy for ASD sagittal correction. They can be used as well for the
      interpretation of clinical series in ASD.

PMID- 24917480
TI  - Association Between SLC6A4 Serotonin Transporter Gene Lainked Polymorphic Region
      and ADRA2A -1291C>G and Irritable Bowel Syndrome in Korea.
AB  - BACKGROUND/AIMS: Despite numerous studies on the relation of genetic
      polymorphisms with irritable bowel syndrome (IBS), the results still remain
      inconclusive. The aim of this study was to assess the possible association
      between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR),
      ADRA2A -1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms
      and IBS based on Rome III criteria in Korea. METHODS: Study subjects were
      prospectively recruited from visitors to Seoul National University Bundang
      Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171
      healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were
      genotyped. Serum serotonin from 101 participants was measured by ELISA and
      compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. RESULTS:
      Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated
      with the total IBS, constipation predominant IBS (IBS-C) and mixture of diarrhea
      and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR:
      11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33,
      respectively). Carrying ADRA2A -1291G allele was significantly associated with
      total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and
      adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed
      reduced level of serum serotonin compared to controls and patients with diarrhea
      predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P =
      0.001, respectively). CONCLUSIONS: Genetic polymorphisms of SLC6A4 5-HTTLPR and
      ADRA2A -1291C>G could be one of the pathophysiological factors of IBS in Korea.
      Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in
      IBS, but large study is needed for confirming genotypic difference in serum
      serotonin level.

PMID- 24917481
TI  - An Interesting Case of Post-fundoplication Dysphagia.

PMID- 24917482
TI  - Estimating quantitative genetic parameters in wild populations: a comparison of
      pedigree and genomic approaches.
AB  - The estimation of quantitative genetic parameters in wild populations is
      generally limited by the accuracy and completeness of the available pedigree
      information. Using relatedness at genomewide markers can potentially remove this
      limitation and lead to less biased and more precise estimates. We estimated
      heritability, maternal genetic effects and genetic correlations for body size
      traits in an unmanaged long-term study population of Soay sheep on St Kilda using
      three increasingly complete and accurate estimates of relatedness: (i) Pedigree
      1, using observation-derived maternal links and microsatellite-derived paternal
      links; (ii) Pedigree 2, using SNP-derived assignment of both maternity and
      paternity; and (iii) whole-genome relatedness at 37 037 autosomal SNPs. In
      initial analyses, heritability estimates were strikingly similar for all three
      methods, while standard errors were systematically lower in analyses based on
      Pedigree 2 and genomic relatedness. Genetic correlations were generally strong,
      differed little between the three estimates of relatedness and the standard
      errors declined only very slightly with improved relatedness information. When
      partitioning maternal effects into separate genetic and environmental components,
      maternal genetic effects found in juvenile traits increased substantially across
      the three relatedness estimates. Heritability declined compared to parallel
      models where only a maternal environment effect was fitted, suggesting that
      maternal genetic effects are confounded with direct genetic effects and that more
      accurate estimates of relatedness were better able to separate maternal genetic
      effects from direct genetic effects. We found that the heritability captured by
      SNP markers asymptoted at about half the SNPs available, suggesting that denser
      marker panels are not necessarily required for precise and unbiased heritability
      estimates. Finally, we present guidelines for the use of genomic relatedness in
      future quantitative genetics studies in natural populations. 

PMID- 24917484
TI  - Stumbling into sexual crime: the passive perpetrator in accounts by male internet
      sex offenders.
AB  - Public reactions to internet child offending remain ambivalent in that, while
      there is vocal condemnation of contact child sex offending, there is less
      indignation about internet child abuse. This is potentially due to a lack of
      recognition of this type of offence as sexual offending per se. This ambiguity is
      reflected by internet sex offenders themselves in their verbalizations of their
      offending. This article presents a qualitative analysis of the accounts offered
      by seven individuals convicted of internet-based sexual offences involving the
      downloading and viewing of images of children. In particular, this article
      presents an analysis of the explanations of offenders for the commencement of
      internet activity and the progression to more illicit online materials. The data
      were collected through semi-structured interviews and analyzed using discursive
      methods, paying close attention to language use and function. The analysis
      documented the practices that internet child abusers employed in order to manage
      their identities, distance themselves from the label of sex offender, and/or
      reduce their personal agency and accountability. Implications of this analysis
      are discussed with reference to the current minimization of the downloading of
      sexually explicit images of children as a sexual crime per se by the public and
      offenders alike and the risk assessment and treatment of individuals convicted of
      these offences. 

PMID- 24917483
TI  - Oligomerization and nanocluster organization render specificity.
AB  - Nanoclusters are anchored to membranes, either within them or in the cytoplasm
      latched onto the cytoskeleton, whose reorganization can regulate their activity.
      Nanoclusters have been viewed in terms of cooperativity and activation; here we
      perceive nanocluster organization from a conformational standpoint. This leads us
      to suggest that while single molecules encode activity, nanoclusters induce
      specificity, and that this is their main evolutionary aim. Distinct, isoform
      specific nanocluster organization can drive the preferred effector (and ligand)
      interactions and thereby designate signalling pathways. The absence of detailed
      structural information across the nanocluster, due to size and dynamics, hinders
      an in-depth grasp of its mechanistic features; however, available data already
      capture some of the principles and their functional 'raison d'etre'.
      Collectively, clustering lends stability and reduces the likelihood of
      proteolytic cleavage; it also increases the effective local concentration and
      enables efficient cooperative activation. However, clustering does not determine
      the ability of the single molecule to function. Drugs targeting nanoclusters can
      attenuate activity by hampering cooperativity; however, this may not perturb
      activation and signalling, which originate from the molecules themselves, and as
      such, are likely to endure. What then is the major role of nanoclustering?
      Assuming that single molecules evolved first, with a subsequent increase in
      cellular complexity and emergence of highly similar isoform variants, evolution
      faced the threat of signalling promiscuity. We reason that this potential risk
      was thwarted by oligomerization and clustering; clustering confers higher
      specificity, and a concomitant extra layer of cellular control. In our Ras
      example, signalling will be more accurate as a dimer than as a monomer, where its
      isomer specificity could be compromised. 

PMID- 24917485
TI  - Treatment for continuous spikes and waves during sleep (CSWS): survey on
      treatment choices in North America.
AB  - OBJECTIVE: Current literature does not allow an evidence-based approach to the
      treatment of continuous spikes and waves during sleep (CSWS). The aim of this
      study was to describe treatment choices made by clinicians caring for patients
      with CSWS in North America. METHODS: A 24-question survey on treatment choices
      for CSWS was distributed to the members of the American Epilepsy Society (AES).
      The survey presented a clinical vignette of CSWS. The questions addressed
      treatment choices for that clinical scenario. Surveys were self-administered and
      collected using an online survey website (www.surveymonkey.com). RESULTS: Two
      hundred thirty-two surveys were completed. Prominent sleep-potentiated spiking
      was considered to warrant treatment by 81% of respondents. The proportion of
      patients in whom cognitive improvement occurs when sleep-potentiated spiking is
      effectively treated is in >75% of patients (according to 16% of respondents), in
      25-75% of patients (according to 52% of respondents), in <25% of patients
      (according to 20% of respondents), and no or unclear cognitive changes (according
      to 12% of respondents). The preferred first choice to reduce sleep-potentiated
      epileptiform activity was high-dose benzodiazepines (47%), valproate (26%), and
      corticosteroids (15%). The preferred second-choice was valproate (26%), high-dose
      benzodiazepines (24%), and corticosteroids (23%). Among high-dose
      benzodiazepines, the preferred one was diazepam 1 mg/kg for one night followed by
      0.5 mg/kg/day. The preferred dose of valproate was 30-49 mg/kg/day. Among
      corticosteroids the preferred choice was oral prednisone 2 mg/kg/day. The most
      commonly considered endpoints of treatment efficacy were (in decreasing order):
      response of epileptiform activity in electroencephalography (EEG), cognitive
      function, and seizure reduction. Results were consistent among respondents with
      different levels of training and clinical experience. There were differences in
      conceptualization and treatment approaches between pediatric and adult
      neurologists. SIGNIFICANCE: Most clinicians considered that prominent sleep
      potentiated epileptiform activity should be treated. There was no agreement on
      best treatment, but potential candidates included high-dose benzodiazepines,
      valproate, levetiracetam, and corticosteroids.

PMID- 24917486
TI  - Survival analysis of platinum-refractory patients with advanced esophageal cancer
      treated with docetaxel or best supportive care alone: a retrospective study.
AB  - The survival benefit of second-line chemotherapy with docetaxel in platinum
      refractory patients with advanced esophageal cancer (AEC) remains unclear. A
      retrospective analysis of AEC patients with Eastern Cooperative Oncology Group
      performance status (PS)<=2 was performed, and major organ functions were
      preserved, who determined to receive docetaxel or best supportive care (BSC)
      alone after failure of platinum-based chemotherapy. The post-progression survival
      (PPS), defined as survival time after disease progression following platinum
      based chemotherapy, was analyzed by multivariate Cox regression analysis using
      factors identified as significant in univariate analysis of various 20
      characteristics (age, sex, PS, primary tumor location, etc) including Glasgow
      prognostic score (GPS), which is a well-known prognostic factor in many malignant
      tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC
      between January 2007 and December 2011, respectively. The median PPS was 5.4
      months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3
      months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38
      0.84, P=0.005). Univariate analysis revealed six significant factors: treatment,
      PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis.
      Multivariate analysis including these significant factors revealed three
      independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99,
      P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis
      (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the
      docetaxel group compared with patients who refused docetaxel treatment in the BSC
      group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have
      prolonged survival in platinum-refractory patients with AEC.

PMID- 24917488
TI  - Combining physiological threshold knowledge to species distribution models is key
      to improving forecasts of the future niche for macroalgae.
AB  - Species distribution models (SDM) are a useful tool for predicting species range
      shifts in response to global warming. However, they do not explore the mechanisms
      underlying biological processes, making it difficult to predict shifts outside
      the environmental gradient where the model was trained. In this study, we combine
      correlative SDMs and knowledge on physiological limits to provide more robust
      predictions. The thermal thresholds obtained in growth and survival experiments
      were used as proxies of the fundamental niches of two foundational marine
      macrophytes. The geographic projections of these species' distributions obtained
      using these thresholds and existing SDMs were similar in areas where the species
      are either absent-rare or frequent and where their potential and realized niches
      match, reaching consensus predictions. The cold-temperate foundational seaweed
      Himanthalia elongata was predicted to become extinct at its southern limit in
      northern Spain in response to global warming, whereas the occupancy of southern
      lusitanic Bifurcaria bifurcata was expected to increase. Combined approaches such
      as this one may also highlight geographic areas where models disagree potentially
      due to biotic factors. Physiological thresholds alone tended to over-predict
      species prevalence, as they cannot identify absences in climatic conditions
      within the species' range of physiological tolerance or at the optima. Although
      SDMs tended to have higher sensitivity than threshold models, they may include
      regressions that do not reflect causal mechanisms, constraining their predictive
      power. We present a simple example of how combining correlative and mechanistic
      knowledge provides a rapid way to gain insight into a species' niche resulting in
      consistent predictions and highlighting potential sources of uncertainty in
      forecasted responses to climate change. 

PMID- 24917487
TI  - Patterns and predictors of attrition in a trial of a housing intervention for
      homeless people with mental illness.
AB  - PURPOSE: Participant retention is an important challenge in longitudinal research
      on homeless people. High attrition can threaten validity, and may represent lost
      opportunities to deliver interventions. In this article, we report on attrition
      in the At Home/Chez Soi study, a multi-site randomized controlled trial of a
      housing intervention for homeless people with mental illness. METHODS: We first
      calculate life tables, and then use clustered logistic regression to implement a
      discrete-time survival model. We use splines and indicator variables to capture
      non-linear and group-specific variation over time in the hazard function. As
      potential predictors, we consider study group, site, date of recruitment, age,
      sex, baseline substance dependence, baseline psychotic disorder, time homeless in
      life, community functioning, and education. RESULTS: The study recruited 2,148
      homeless people with mental illness. Of these, 1,158 were randomized to the
      housing first intervention (HF), and 990 to treatment as usual (TAU). Excluding
      79 people known to have died, attrition was 14%. This proportion was higher in
      TAU than in HF (21 vs. 8%, p < 0.01). Attrition was significantly lower in one
      site than elsewhere, and was also lower among those with substance dependence (13
      vs. 18%, p < 0.01) and among those enrolled earlier in the study. The hazard
      varied over time in complex ways. CONCLUSIONS: Results imply that study factors
      are more important than participant characteristics as determinants of retention,
      and that the immediate period after randomization is a crucial one. The high
      overall retention demonstrates the effectiveness of existing techniques for
      retaining participants.

PMID- 24917489
TI  - Design of a flexible component gathering algorithm for converting cell-based
      models to graph representations for use in evolutionary search.
AB  - BACKGROUND: The ability of science to produce experimental data has outpaced the
      ability to effectively visualize and integrate the data into a conceptual
      framework that can further higher order understanding. Multidimensional and shape
      based observational data of regenerative biology presents a particularly daunting
      challenge in this regard. Large amounts of data are available in regenerative
      biology, but little progress has been made in understanding how organisms such as
      planaria robustly achieve and maintain body form. An example of this kind of data
      can be found in a new repository (PlanformDB) that encodes descriptions of
      planaria experiments and morphological outcomes using a graph formalism. RESULTS:
      We are developing a model discovery framework that uses a cell-based modeling
      platform combined with evolutionary search to automatically search for and
      identify plausible mechanisms for the biological behavior described in
      PlanformDB. To automate the evolutionary search we developed a way to compare the
      output of the modeling platform to the morphological descriptions stored in
      PlanformDB. We used a flexible connected component algorithm to create a graph
      representation of the virtual worm from the robust, cell-based simulation data.
      These graphs can then be validated and compared with target data from PlanformDB
      using the well-known graph-edit distance calculation, which provides a
      quantitative metric of similarity between graphs. The graph edit distance
      calculation was integrated into a fitness function that was able to guide
      automated searches for unbiased models of planarian regeneration. We present a
      cell-based model of planarian that can regenerate anatomical regions following
      bisection of the organism, and show that the automated model discovery framework
      is capable of searching for and finding models of planarian regeneration that
      match experimental data stored in PlanformDB. CONCLUSION: The work presented
      here, including our algorithm for converting cell-based models into graphs for
      comparison with data stored in an external data repository, has made feasible the
      automated development, training, and validation of computational models using
      morphology-based data. This work is part of an ongoing project to automate the
      search process, which will greatly expand our ability to identify, consider, and
      test biological mechanisms in the field of regenerative biology.

PMID- 24917490
TI  - Genetic polymorphisms altering microRNA activity in psoriasis--a key to solve the
      puzzle of missing heritability?
AB  - Psoriasis is a chronic immune-mediated skin disease in which the balance in the
      interplay of immune cells and keratinocytes is disturbed. MicroRNAs (miRNAs) are
      endogenous small regulatory RNAs that stabilize cellular phenotypes and fine-tune
      signal transduction feedback loops through the regulation of gene networks.
      Through the regulation of their multiple target genes, miRNAs regulate the
      development of inflammatory cell subsets and have a significant impact on the
      magnitude of inflammatory responses. Since the discovery of deregulated miRNA
      expression in psoriasis, we have learned that they can regulate differentiation,
      proliferation and cytokine response of keratinocytes, activation and survival of
      T cells and the crosstalk between immunocytes and keratinocytes through the
      regulation of chemokine production. In recent years, it became apparent that
      genetic polymorphisms in miRNA genes and/or in miRNA binding sites of target
      genes can affect miRNA activity and contribute to disease susceptibility.
      Psoriasis has a strong genetic background; however, the contribution of genetic
      variants involving miRNAs is largely unexplored in psoriasis. We propose that
      changes in miRNA-mediated gene regulation may be a major contributor to the
      disturbed balance in immune regulation that results in chronic skin inflammation.
      In this viewpoint essay, we focus on the emerging new aspects of the role of
      miRNAs in psoriasis and propose that genetic polymorphisms that affect miRNA
      activity might be important in the pathogenesis of psoriasis. 

PMID- 24917491
TI  - Cranial metastatic alveolar rhabdomyosarcoma mimicking hematological malignancy
      in an adolescent boy.
AB  - BACKGROUND: Widespread alveolar rhabdomyosarcoma (ARMS) with bone marrow
      involvement and with an unknown primary tumor, especially presenting with acute
      tumor lysis syndrome can be easily misdiagnosed as a hematological malignancy.
      Furthermore, brain metastasis of ARMS is rare seen in children. CASE REPORT:
      Herein, we report a 14-year-old boy presenting with acute tumor lysis syndrome
      due to bone marrow invasion of ARMS, who was diagnosed after abdominal paraaortic
      lymph node biopsy. Despite radiological and nuclear medicine imaging, the primary
      tumor site could not be found. He was treated with vincristine, topotecan, and
      cyclophosphamide for 42 weeks. Six months after the completion of treatment, he
      suffered from severe headache, blurred vision, right hemiplegia, and severe bone
      pain. Cranial magnetic resonance imaging showed multiple hemorrhagic infarctions.
      Brain biopsy showed brain metastasis with PAX3-FKHR fusion transcript.
      CONCLUSION: The clinicians must be vigilant about solely brain metastasis in ARMS
      without additional metastasis.

PMID- 24917492
TI  - Results of posterior cranial vault remodeling for plagiocephaly and brachycephaly
      by the meander technique.
AB  - OBJECTIVE: Several techniques to remodel the posterior calvarium in order to
      increase intracranial volume (ICV) and to improve cosmetic appearance are
      reported. This study presents the results of meander technique in patients with
      brachycephaly and posterior plagiocephaly. METHODS: During December 2011 and July
      2013, a total of 12 children (median age: 15 months) underwent posterior cranial
      vault remodeling by the meander technique (brachycephaly, n = 6; posterior
      plagiocephaly, n = 6). The available pre- and postoperative MRIs were assessed
      with regard to ICV, cranial index (CI) and asymmetry index (AI) as well as the
      position of the cerebellar tonsils. RESULTS: No intra- or postoperative
      complications were observed. Blood transfusions were necessary in nine of 12
      patients. A significant increase of the ICV from 1,178.4 +/- 134.5 to 1,293.0 +/-
      137.5 cm(3) (p < 0.05) is demonstrated. In the patients with brachycephaly the CI
      was significantly improved from 0.97 +/- 0.12 to 0.89 +/- 0.12 postoperatively (p
      < 0.05). The AI in patients with posterior plagiocephaly was significantly
      ameliorated from 0.83 +/- 0.04 to 0.92 +/- 0.02 postoperatively (p < 0.05). There
      was a significant effect on cerebellar tonsil position in relation to foramen
      magnum level for patients with brachycephaly (right tonsil: 11.9 +/- 9.2 to 7.0
      +/- 9.1 mm, p < 0.05; left: 10.8 +/- 9.5 to 9.7 +/- 10.6 mm; p < 0.05) as well as
      in posterior plagiocephaly for the ipsilateral tonsil (3.2 +/- 3.5 to 1.6 +/- 3.5
      mm; p < 0.01). CONCLUSION: The presented surgical technique is considered to be
      safe. The technique is capable to significantly increase ICV and improve cosmetic
      appearance of the remodeled calvarium. Further evidence that posterior cranial
      vault remodeling influences the position of the cerebellar tonsils is added by
      the results of the study.

PMID- 24917493
TI  - Improving management support tools for reintroducing bivalve species (eastern
      oyster [Crassostrea virginica Gmelin]) in urban estuaries.
AB  - Successful reintroduction of "ecologically extinct" bivalve species into
      anthropogenically impaired urban estuaries is problematic when employing existing
      management tools used in estuaries where bivalves are present (GIS-based
      restoration models, expanding existing shellfish beds, placement of shell
      substrate, physical oceanographic parameters). A significant management challenge
      is appropriate site selection. We are proposing the inclusion of a biological
      parameter (evaluation of tissue histopathology) in an inexpensive and rapid site
      selection model to inform management decision making and identify sites with the
      greatest potential for reintroduction success. Use of biological biomarkers is
      not a new concept, but it is important that they be included in a multitiered
      management approach to bivalve reintroduction. This Case Study tested adult
      Eastern Oysters (Crassostrea virginica Gmelin) from locations that supported
      comparable short-term survival rates by evaluating growth and tissue health
      and/or disease. Biomarkers indicated oyster tissues at one site were normal, the
      female:male sex ratio was 50:50, and female oysters were in spawning condition.
      Conversely, oyster tissues at the second site exhibited multiple abnormalities,
      samples were 100% male, and the incidence of disease was high. Using the
      biomarker tool, we evaluated 4 additional sites where oysters exhibited short
      term (1 year) survival. At 2 locations, we observed chronic health impacts that
      would preclude reintroduction, including samples from one site where a wild
      population was surviving. We also analyzed tissue and shell heavy metal contents.
      Soft tissue metal concentrations in Meadowlands samples were at the high range of
      scientific literature values, averaging 1.1% of total body weight, whereas tissue
      metal concentrations at the Keyport site were within acceptable ranges. Although
      initial survival and growth rates at both locations were comparable, site
      specific urban stressors reduced oyster fitness at 1 of the 2 locations. We are
      proposing an Estuarine Reintroduction Site Selection Model, which includes a
      biological in situ parameter, to increase the probability of successfully
      managing a sustainable oyster reintroduction before commencing expensive large
      scale restoration activities.

PMID- 24917494
TI  - Dyadic Event Attribution in Social Networks with Mixtures of Hawkes Processes.
AB  - In many applications in social network analysis, it is important to model the
      interactions and infer the influence between pairs of actors, leading to the
      problem of dyadic event modeling which has attracted increasing interests
      recently. In this paper we focus on the problem of dyadic event attribution, an
      important missing data problem in dyadic event modeling where one needs to infer
      the missing actor-pairs of a subset of dyadic events based on their observed
      timestamps. Existing works either use fixed model parameters and heuristic rules
      for event attribution, or assume the dyadic events across actor-pairs are
      independent. To address those shortcomings we propose a probabilistic model based
      on mixtures of Hawkes processes that simultaneously tackles event attribution and
      network parameter inference, taking into consideration the dependency among
      dyadic events that share at least one actor. We also investigate using additive
      models to incorporate regularization to avoid overfitting. Our experiments on
      both synthetic and real-world data sets on international armed conflicts suggest
      that the proposed new method is capable of significantly improve accuracy when
      compared with the state-of-the-art for dyadic event attribution.

PMID- 24917495
TI  - An interview with Phil Ingham.

PMID- 24917496
TI  - How to make a hippocampal dentate gyrus granule neuron.
AB  - Granule neurons in the hippocampal dentate gyrus (DG) receive their primary
      inputs from the cortex and are known to be continuously generated throughout
      adult life. Ongoing integration of newborn neurons into the existing hippocampal
      neural circuitry provides enhanced neuroplasticity, which plays a crucial role in
      learning and memory; deficits in this process have been associated with cognitive
      decline under neuropathological conditions. In this Primer, we summarize the
      developmental principles that regulate the process of DG neurogenesis and discuss
      recent advances in harnessing these developmental cues to generate DG granule
      neurons from human pluripotent stem cells.

PMID- 24917498
TI  - Combinatorial actions of Tgfbeta and Activin ligands promote oligodendrocyte
      development and CNS myelination.
AB  - In the embryonic CNS, development of myelin-forming oligodendrocytes is limited
      by bone morphogenetic proteins, which constitute one arm of the transforming
      growth factor-beta (Tgfbeta) family and signal canonically via Smads 1/5/8.
      Tgfbeta ligands and Activins comprise the other arm and signal via Smads 2/3, but
      their roles in oligodendrocyte development are incompletely characterized. Here,
      we report that Tgfbeta ligands and activin B (ActB) act in concert in the
      mammalian spinal cord to promote oligodendrocyte generation and myelination. In
      mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first
      exposed to Tgfbeta ligands in isolation, then later in combination with ActB
      during maturation. In primary OLP cultures, Tgfbeta1 and ActB differentially
      activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands
      enhance viability, and Tgfbeta1 promotes proliferation while ActB supports
      maturation. Importantly, co-treatment strongly activates both signaling pathways,
      producing an additive effect on viability and enhancing both proliferation and
      differentiation such that mature oligodendrocyte numbers are substantially
      increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and
      maturing oligodendrocytes in spinal cord white matter display strong Smad3 and
      MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos,
      apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently
      reduced, but numbers, maturation and myelination recover during the first
      postnatal week. Smad3(-/-) mice display a more severe phenotype, including
      diminished viability and proliferation, persistently reduced mature and immature
      cell numbers, and delayed myelination. Collectively, these findings suggest that,
      in mammalian spinal cord, Tgfbeta ligands and ActB together support
      oligodendrocyte development and myelin formation.

PMID- 24917497
TI  - Chromatin features and the epigenetic regulation of pluripotency states in ESCs.
AB  - In pluripotent stem cells, the interplay between signaling cues, epigenetic
      regulators and transcription factors orchestrates developmental potency.
      Flexibility in gene expression control is imparted by molecular changes to the
      nucleosomes, the building block of chromatin. Here, we review the current
      understanding of the role of chromatin as a plastic and integrative platform to
      direct gene expression changes in pluripotent stem cells, giving rise to distinct
      pluripotent states. We will further explore the concept of epigenetic asymmetry,
      focusing primarily on histone stoichiometry and their associated modifications,
      that is apparent at both the nucleosome and chromosome-wide levels, and discuss
      the emerging importance of these asymmetric chromatin configurations in
      diversifying epigenetic states and their implications for cell fate control.

PMID- 24917499
TI  - Stochastic specification of primordial germ cells from mesoderm precursors in
      axolotl embryos.
AB  - A common feature of development in most vertebrate models is the early
      segregation of the germ line from the soma. For example, in Xenopus and zebrafish
      embryos primordial germ cells (PGCs) are specified by germ plasm that is
      inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the
      commitment of cells to the germ line. How these disparate mechanisms of PGC
      specification evolved is unknown. Here, in order to identify the ancestral
      mechanism of PGC specification in vertebrates, we studied PGC specification in
      embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor.
      In the axolotl, PGCs develop within mesoderm, and classic studies have reported
      their induction from primitive ectoderm (animal cap). We used an axolotl animal
      cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The
      role of FGF was then confirmed in vivo. We also showed PGC induction by
      Brachyury, in the presence of BMP4. These conditions induced pluripotent
      mesodermal precursors that give rise to a variety of somatic cell types, in
      addition to PGCs. Irreversible restriction of the germ line did not occur until
      the mid-tailbud stage, days after the somatic germ layers are established. Before
      this, germline potential was maintained by MAP kinase signalling. We propose that
      this stochastic mechanism of PGC specification, from mesodermal precursors, is
      conserved in vertebrates.

PMID- 24917500
TI  - Notch signaling functions in lymphatic valve formation.
AB  - Collecting lymphatic ducts contain intraluminal valves that prevent backflow. In
      mice, lymphatic valve morphogenesis begins at embryonic day 15.5 (E15.5). In the
      mesentery, Prox1 expression is high in valve-forming lymphatic endothelial cells,
      whereas cells of the lymphatic ducts express lower levels of Prox1. Integrin
      alpha9, fibronectin EIIIA, Foxc2, calcineurin and the gap junction protein Cx37
      are required for lymphatic valve formation. We show that Notch1 is expressed
      throughout the developing mesenteric lymphatic vessels at E16.5, and that, by
      E18.5, Notch1 expression becomes highly enriched in the lymphatic valve
      endothelial cells. Using a Notch reporter mouse, Notch activity was detected in
      lymphatic valves at E17.5 and E18.5. The role of Notch in lymphatic valve
      morphogenesis was studied using a conditional lymphatic endothelial cell driver
      either to delete Notch1 or to express a dominant-negative Mastermind-like
      (DNMAML) transgene. Deletion of Notch1 led to an expansion of Prox1(high) cells,
      a defect in Prox1(high) cell reorientation and a decrease in integrin alpha9
      expression at sites of valve formation. Expression of DNMAML, which blocks all
      Notch signaling, resulted in a more severe phenotype characterized by a decrease
      in valves, failure of Prox1(high) cells to cluster, and rounding of the nuclei
      and decreased fibronectin-EIIIA expression in the Prox1(high) cells found at
      valve sites. In human dermal lymphatic endothelial cells, activation of Notch1 or
      Notch4 induced integrin alpha9, fibronectin EIIIA and Cx37 expression. We
      conclude that Notch signaling is required for proper lymphatic valve formation
      and regulates integrin alpha9 and fibronectin EIIIA expression during valve
      morphogenesis.

PMID- 24917502
TI  - Sema6a and Plxna2 mediate spatially regulated repulsion within the developing eye
      to promote eye vesicle cohesion.
AB  - Organs are generated from collections of cells that coalesce and remain together
      as they undergo a series of choreographed movements to give the organ its final
      shape. We know little about the cellular and molecular mechanisms that regulate
      tissue cohesion during morphogenesis. Extensive cell movements underlie eye
      development, starting with the eye field separating to form bilateral vesicles
      that go on to evaginate from the forebrain. What keeps eye cells together as they
      undergo morphogenesis and extensive proliferation is unknown. Here, we show that
      plexina2 (Plxna2), a member of a receptor family best known for its roles in axon
      and cell guidance, is required alongside the repellent semaphorin 6a (Sema6a) to
      keep cells integrated within the zebrafish eye vesicle epithelium. sema6a is
      expressed throughout the eye vesicle, whereas plxna2 is restricted to the ventral
      vesicle. Knockdown of Plxna2 or Sema6a results in a loss of vesicle integrity,
      with time-lapse microscopy showing that eye progenitors either fail to enter the
      evaginating vesicles or delaminate from the eye epithelium. Explant experiments,
      and rescue of eye vesicle integrity with simultaneous knockdown of sema6a and
      plxna2, point to an eye-autonomous requirement for Sema6a/Plxna2. We propose a
      novel, tissue-autonomous mechanism of organ cohesion, with neutralization of
      repulsion suggested as a means to promote interactions between cells within a
      tissue domain.

PMID- 24917503
TI  - A regulatory receptor network directs the range and output of the Wingless
      signal.
AB  - The potent activity of Wnt/Wingless (Wg) signals necessitates sophisticated
      mechanisms that spatially and temporally regulate their distribution and range of
      action. The two main receptor components for Wg - Arrow (Arr) and Frizzled 2
      (Fz2) - are transcriptionally downregulated by Wg signaling, thus forming
      gradients that oppose that of Wg. Here, we analyze the relevance of this
      transcriptional regulation for the formation of the Wg gradient in the Drosophila
      wing disc by combining in vivo receptor overexpression with an in silico model of
      Wg receptor interactions. Our experiments show that ubiquitous upregulation of
      Arr and Fz2 has no significant effects on Wg output, whereas clonal
      overexpression of these receptors leads to signaling discontinuities that have
      detrimental phenotypic consequences. These findings are supported by our in
      silico model for Wg diffusion and signal transduction, which suggests that abrupt
      changes in receptor levels causes discontinuities in Wg signaling. Furthermore,
      we identify a 200 bp regulatory element in the arr locus that can account for the
      Arr gradient, and we show that this is indirectly negatively controlled by Wg
      activity. Finally, we analyze the role of Frizzled 3 (Fz3) in this system and
      find that its expression, which is induced by Wg, contributes to the
      establishment of the Arr and Fz2 gradients through counteracting canonical
      signaling. Taken together, our results provide a model in which the regulatory
      network of Wg and the three receptor components account for the range and shape
      of this prototypical morphogen system.

PMID- 24917501
TI  - A neuron autonomous role for the familial dysautonomia gene ELP1 in sympathetic
      and sensory target tissue innervation.
AB  - Familial dysautonomia (FD) is characterized by severe and progressive sympathetic
      and sensory neuron loss caused by a highly conserved germline point mutation of
      the human ELP1/IKBKAP gene. Elp1 is a subunit of the hetero-hexameric
      transcriptional elongator complex, but how it functions in disease-vulnerable
      neurons is unknown. Conditional knockout mice were generated to characterize the
      role of Elp1 in migration, differentiation and survival of migratory neural crest
      (NC) progenitors that give rise to sympathetic and sensory neurons. Loss of Elp1
      in NC progenitors did not impair their migration, proliferation or survival, but
      there was a significant impact on post-migratory sensory and sympathetic neuron
      survival and target tissue innervation. Ablation of Elp1 in post-migratory
      sympathetic neurons caused highly abnormal target tissue innervation that was
      correlated with abnormal neurite outgrowth/branching and abnormal cellular
      distribution of soluble tyrosinated alpha-tubulin in Elp1-deficient primary
      sympathetic and sensory neurons. These results indicate that neuron loss and
      physiologic impairment in FD is not a consequence of abnormal neuron progenitor
      migration, differentiation or survival. Rather, loss of Elp1 leads to neuron
      death as a consequence of failed target tissue innervation associated with
      impairments in cytoskeletal regulation.

PMID- 24917504
TI  - The facial neural crest controls fore- and midbrain patterning by regulating
      Foxg1 expression through Smad1 activity.
AB  - The facial neural crest (FNC), a pluripotent embryonic structure forming
      craniofacial structures, controls the activity of brain organisers and stimulates
      cerebrum growth. To understand how the FNC conveys its trophic effect, we have
      studied the role of Smad1, which encodes an intracellular transducer, to which
      multiple signalling pathways converge, in the regulation of Foxg1. Foxg1 is a
      transcription factor essential for telencephalic specification, the mutation of
      which leads to microcephaly and mental retardation. Smad1 silencing, based on RNA
      interference (RNAi), was performed in pre-migratory FNC cells. Soon after
      electroporation of RNAi molecules, Smad1 inactivation abolished the expression of
      Foxg1 in the chick telencephalon, resulting in dramatic microcephaly and partial
      holoprosencephaly. In addition, the depletion of Foxg1 activity altered the
      expression Otx2 and Foxa2 in di/mesencephalic neuroepithelium. However, when
      mutated forms of Smad1 mediating Fgf and Wnt signalling were transfected into FNC
      cells, these defects were overcome. We also show that, downstream of Smad1
      activity, Dkk1, a Wnt antagonist produced by the FNC, initiated the specification
      of the telencephalon by regulating Foxg1 activity. Additionally, the activity of
      Cerberus in FNC-derived mesenchyme synergised with Dkk1 to control Foxg1
      expression and maintain the balance between Otx2 and Foxa2.

PMID- 24917505
TI  - Cadherin 6 promotes neural crest cell detachment via F-actin regulation and
      influences active Rho distribution during epithelial-to-mesenchymal transition.
AB  - The epithelial-to-mesenchymal transition (EMT) is a complex change in cell
      phenotype that is important for cell migration, morphogenesis and carcinoma
      metastasis. Loss of epithelial cell adhesion and tight regulation of cadherin
      adhesion proteins are crucial for EMT. Cells undergoing EMT often display
      cadherin switching, where they downregulate one cadherin and induce expression of
      another. However, the functions of the upregulated cadherins and their effects on
      cell motility are poorly understood. Neural crest cells (NCCs), which undergo EMT
      during development, lose N-cadherin and upregulate Cadherin 6 (Cdh6) prior to
      EMT. Cdh6 has been suggested to suppress EMT via cell adhesion, but also to
      promote EMT by mediating pro-EMT signals. Here, we determine novel roles for Cdh6
      in generating cell motility during EMT. We use live imaging of NCC behavior in
      vivo to show that Cdh6 promotes detachment of apical NCC tails, an important
      early step of EMT. Furthermore, we show that Cdh6 affects spatiotemporal dynamics
      of F-actin and active Rho GTPase, and that Cdh6 is required for accumulation of F
      actin in apical NCC tails during detachment. Moreover, Cdh6 knockdown alters the
      subcellular distribution of active Rho, which is known to promote localized
      actomyosin contraction that is crucial for apical NCC detachment. Together, these
      data suggest that Cdh6 is an important determinant of where subcellular
      actomyosin forces are generated during EMT. Our results also identify mechanisms
      by which an upregulated cadherin can generate cell motility during EMT.

PMID- 24917506
TI  - Atlas-builder software and the eNeuro atlas: resources for developmental biology
      and neuroscience.
AB  - A major limitation in understanding embryonic development is the lack of cell
      type-specific markers. Existing gene expression and marker atlases provide
      valuable tools, but they typically have one or more limitations: a lack of single
      cell resolution; an inability to register multiple expression patterns to
      determine their precise relationship; an inability to be upgraded by users; an
      inability to compare novel patterns with the database patterns; and a lack of
      three-dimensional images. Here, we develop new 'atlas-builder' software that
      overcomes each of these limitations. A newly generated atlas is three
      dimensional, allows the precise registration of an infinite number of cell type
      specific markers, is searchable and is open-ended. Our software can be used to
      create an atlas of any tissue in any organism that contains stereotyped cell
      positions. We used the software to generate an 'eNeuro' atlas of the Drosophila
      embryonic CNS containing eight transcription factors that mark the major CNS cell
      types (motor neurons, glia, neurosecretory cells and interneurons). We found
      neuronal, but not glial, nuclei occupied stereotyped locations. We added 75 new
      Gal4 markers to the atlas to identify over 50% of all interneurons in the ventral
      CNS, and these lines allowed functional access to those interneurons for the
      first time. We expect the atlas-builder software to benefit a large proportion of
      the developmental biology community, and the eNeuro atlas to serve as a publicly
      accessible hub for integrating neuronal attributes - cell lineage, gene
      expression patterns, axon/dendrite projections, neurotransmitters--and linking
      them to individual neurons.

PMID- 24917508
TI  - Arthroscopic evaluation for omalgia patients undergoing the clavicular hook plate
      fixation of distal clavicle fractures.
AB  - BACKGROUND: The aim of this study is to investigate the anatomic changes in the
      shoulder joints responsible for omalgia after the clavicular hook plate fixation
      under arthroscope. METHODS: Arthroscopic examination was carried out for 12
      omalgia patients who underwent clavicular hook plate fixation due to distal
      clavicle fractures. Functional outcome of shoulder was measured by the Japanese
      Orthopaedic Association (JOA) score before and after the withdrawal of the
      fixation plate. RESULTS: The rotator cuff compression by the clavicular hook was
      arthroscopically observed in 11 of the 12 cases. The JOA scores of the shoulder
      were significantly improved at 1 month after the withdrawal of the fixation plate
      (pain, 28 +/- 2.4 vs. 15 +/- 5.2; function, 19.2 +/- 1.0 vs. 11.7 +/- 1.9; range
      of movements, 26.8 +/- 2.6 vs. 14.8 +/- 3.4) compared with before. CONCLUSIONS:
      The impingement of the hook to the rotator cuff may be the main cause for the
      omalgia. The appropriate hook and plate that fit to the curve of the clavicle as
      well as the acromion are necessary to decrease the severity of omalgia.

PMID- 24917510
TI  - Spatially varying regularization of deconvolution in 3D microscopy.
AB  - Confocal microscopy has become an essential tool to explore biospecimens in 3D.
      Confocal microcopy images are still degraded by out-of-focus blur and Poisson
      noise. Many deconvolution methods including the Richardson-Lucy (RL) method,
      Tikhonov method and split-gradient (SG) method have been well received. The RL
      deconvolution method results in enhanced image quality, especially for Poisson
      noise. Tikhonov deconvolution method improves the RL method by imposing a prior
      model of spatial regularization, which encourages adjacent voxels to appear
      similar. The SG method also contains spatial regularization and is capable of
      incorporating many edge-preserving priors resulting in improved image quality.
      The strength of spatial regularization is fixed regardless of spatial location
      for the Tikhonov and SG method. The Tikhonov and the SG deconvolution methods are
      improved upon in this study by allowing the strength of spatial regularization to
      differ for different spatial locations in a given image. The novel method shows
      improved image quality. The method was tested on phantom data for which ground
      truth and the point spread function are known. A Kullback-Leibler (KL) divergence
      value of 0.097 is obtained with applying spatially variable regularization to the
      SG method, whereas KL value of 0.409 is obtained with the Tikhonov method. In
      tests on a real data, for which the ground truth is unknown, the reconstructed
      data show improved noise characteristics while maintaining the important image
      features such as edges. 

PMID- 24917511
TI  - Sinus sternoclavicularis: a congenital cervical sinus.
AB  - We try to characterize a previously rather neglected congenital cervical sinus
      located in the sternoclavicular area in five children. This sinus showed
      extension to the left sternoclavicular joint in all patients, so we call this
      congenital lesion "sinus sternoclavicularis." With knowledge of this congenital
      lesion, diagnosis can easily be established based on case history and clinical
      examination; no further radiological tests are required. Surgical excision is the
      treatment of choice. The chance of recurrence seems to be high because of
      misinterpretation of the lesion. 

PMID- 24917509
TI  - Comorbidities predict worse prognosis in patients with primary myelofibrosis.
AB  - BACKGROUND: Comorbidities have been shown to play an important role in the
      prognostic assessment of several hematologic conditions; however, the role of
      comorbidities in primary myelofibrosis has not been studied. The objective of the
      current study was to evaluate the prevalence and impact of comorbidities in
      patients with primary myelofibrosis (PMF) using the Adult Comorbidity Evaluation
      27 (ACE-27). METHODS: In this retrospective observational cohort study, a total
      of 349 consecutive patients with a confirmed diagnosis of PMF who presented to
      the study institution from 2000 to 2008 were evaluated. The authors evaluated the
      frequency and severity of comorbidities in these patients and assessed their
      impact on survival in a bivariable model that included the ACE-27 and Dynamic
      International Prognostic Scoring System scores as covariates. RESULTS:
      Approximately 64% of patients had at least 1 comorbid condition, and diseases of
      the cardiovascular system (63%) were most common. Comorbidities had a significant
      negative impact on survival (P < .001). Patients with severe comorbidities had
      twice the risk of death as those with no comorbidities. When stratified by
      demographic and clinical characteristics, comorbidities were found to be
      significantly associated with worse survival in patients aged < 65 years (P <
      .001) and those with an ECOG performance status < 1 (P < .001). In a
      multivariable model that included the ACE-27 and Dynamic International Prognostic
      Scoring System scores, comorbidities retained a significant association with
      shorter survival (P <= .001). CONCLUSIONS: The assessment of comorbid conditions
      in patients with PMF, particularly those who are younger and with a good
      performance status, has important implications for overall prognosis and
      treatment planning.

PMID- 24917512
TI  - Liposarcoma in clownfish, Amphiprion ocellaris Cuvier, produced in indoor
      aquaculture.
AB  - Clownfish, Amphiprion ocellaris Cuvier, produced and grown in an experimental
      indoor aquaculture facility, presented with lipomatous tumours. A total of 14
      affected fish were examined. Based on the total number of fish at the aquaculture
      facility at the time of outbreak of this pathology, the scope of the incident is
      estimated to be 1 of 300 fish. The tumours were characterized by the presence of
      mature adipocytes of variable sizes, lipoblasts and by an invasive behaviour,
      which affected internal organs, muscle, central nervous system and, in one case,
      an eye. Detailed macroscopic and histopathological features are presented. The
      suggested diagnosis is that of a well-differentiated liposarcoma, a diagnosis so
      far never applied to fish. The limited outbreak of the neoplasm lasted a few
      months in 2011 and did not recur. Possible factors leading to this phenomenon,
      notably the metastasis, are discussed. 

PMID- 24917513
TI  - Core-shell structure microcapsules with dual pH-responsive drug release function.
AB  - We report dual pH-responsive microcapsules manufactured by combining
      electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to
      produce monodisperse core (alginate)-shell (chitosan) structure with dual pH
      responsive drug release function. The fabricated core-shell microcapsules were
      size controllable by tuning the synthesis parameters of the ESD and MFD systems,
      and were responsive in both acidic and alkaline environment, We used two model
      drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the
      alginate core) for drug delivery study. The results show that core-shell
      structure microcapsules have better drug release efficiency than respective core
      or shell particles. A biocompatibility test showed that the core-shell structure
      microcapsules presented positive cell viability (above 80%) when evaluated by the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      results indicate that the synthesized core-shell microcapsules were a potential
      candidate of dual-drug carriers.

PMID- 24917514
TI  - Nothosaur foraging tracks from the Middle Triassic of southwestern China.
AB  - The seas of the Mesozoic (266-66 Myr ago) were remarkable for predatory marine
      reptiles, but their modes of locomotion have been debated. One problem has been
      the absence of tracks, although there is no reason to expect that swimmers would
      produce tracks. We report here seabed tracks made by Mesozoic marine reptiles,
      produced by the paddles of nothosaurs (Reptilia, Sauropterygia) in the Middle
      Triassic of the Luoping localities in Yunnan, southwestern China. These show that
      the track-making nothosaurs used their forelimbs for propulsion, they generally
      rowed (both forelimbs operating in unison rather than alternately), and the
      forelimb entered medially, dug in as the paddle tip gained purchase, and withdrew
      cleanly. These inferences may provide evidence for swimming modes, or it could be
      argued that the locomotory modes indicated by the tracks were restricted to such
      contact propulsion. Such punting behaviour may have been used to flush prey from
      the bottom muds.

PMID- 24917516
TI  - Allosteric regulation of the P2X4 receptor channel pore dilation.
AB  - Allosteric modulators of ligand-gated receptor channels induce conformational
      changes of the entire protein that alter potencies and efficacies for orthosteric
      ligands, expressed as the half maximal effective concentration (EC50) and maximum
      current amplitude, respectively. Here, we studied the influence of allostery on
      channel pore dilation, an issue not previously addressed. Experiments were done
      using the rat P2X4 receptor expressed in human embryonic kidney 293T cells and
      gated by adenosine 5'-triphosphate (ATP) in the presence and absence of
      ivermectin (IVM), an established positive allosteric regulator of this channel.
      In the absence of IVM, this channel activates and deactivates rapidly, does not
      show transition from open to dilated states, desensitizes completely with a
      moderate rate, and recovers only fractionally during washout. IVM treatment
      increases the efficacy of ATP to activate the channel and slows receptor
      desensitization during sustained ATP application and receptor deactivation after
      ATP washout. The rescue of the receptor from desensitization temporally coincides
      with pore dilation, and the dilated channel can be reactivated after washout of
      ATP. Experiments with vestibular and transmembrane domain receptor mutants
      further established that IVM has distinct effects on opening and dilation of the
      channel pore, the first accounting for increased peak current amplitude and the
      latter correlating with changes in the EC50 and kinetics of receptor
      deactivation. The corresponding kinetic (Markov state) model indicates that the
      IVM-dependent transition from open to dilated state is coupled to receptor
      sensitization, which rescues the receptor from desensitization and subsequent
      internalization. Allosterically induced sensitization of P2X4R thus provides
      sustained signaling during prolonged and repetitive ATP stimulation. 

PMID- 24917517
TI  - Outcome Indicators for Home Parenteral Nutrition Care: Point of View From Adult
      Patients With Benign Disease.
AB  - BACKGROUND AND AIMS: Patients receiving home parenteral nutrition (HPN) deserve a
      high-quality and patient-centered care. Patient-centered care can be delivered
      only if the patient's priorities and concerns are known. Therefore, the aim is to
      identify the top 3 most important outcome indicators according to patients'
      perspectives and the differences between several centers, HPN regimen, and HPN
      experience. METHODS: A questionnaire, based on previously developed outcome
      indicators, was translated into the mother tongue using forward-backward
      translation and distributed to adult HPN patients with benign disease in March
      2013. To identify differences, a Kruskal-Wallis or Mann-Whitney test was
      performed with GraphPad Prism (significance level <.05) when applicable. RESULTS:
      Nine centers over 8 countries (300 patients) participated. The top 3 outcome
      indicators for patients were (1) incidence of catheter-related infection (CRI),
      (2) survival, and (3) quality of life (QoL). Between the participating centers,
      significant differences on rating were found for 5 outcome indicators (catheter
      obstruction, .015; weight, .002; energy, .010; fear, <.001; and independence,
      .010). The independence outcome indicator (.050) was considered less important
      for experienced (>2 years HPN) vs less experienced patients. For this outcome
      indicator, patients' view also differed significantly based on number of HPN days
      per week (.0103). CONCLUSION: A cohort of HPN patients identified incidence of
      CRI, survival, and QoL as the most important outcome indicators for their care;
      however, there were significant differences between the participating centers.
      For one outcome indicator (independence), there were significant differences
      based on experience and regimen.

PMID- 24917518
TI  - Quantitative longitudinal evaluation of diaschisis-related cerebellar perfusion
      and diffusion parameters in patients with supratentorial hemispheric high-grade
      gliomas after surgery.
AB  - Decreased cerebral blood volume (CBV) in contralateral cerebellar gray matter
      (cGM) in conjunction with cerebellar white matter (cWM) damage, consistent with
      crossed cerebro-cerebellar diaschisis (cCCD) develop following supratentorial
      hemispheric stroke. In this study, we investigated the longitudinal evolution of
      diaschisis-related cerebellar perfusion and diffusion tensor-imaging (DTI)
      changes in patients after surgery for supratentorial brain tumors. Eight patients
      (M:F 5:3, age 8-22 years) who received surgery for supratentorial high-grade
      gliomas were evaluated. Initial MRI studies were performed 19-54 days
      postoperatively, with follow-ups at 2- to 3-month intervals. For each study,
      parametric maps of the cerebellum were generated and coregistered to T1-weighted
      images that had been previously segmented for cGM and cWM. Aggregate mean values
      of CBV, cerebral blood flow (CBF), and fractional anisotropy (FA) were obtained
      separately for cGM and cWM, and asymmetry indices (AIs) were calculated.
      Hemodynamic changes were more robust in cGM than in cWM. Seven patients showed
      decreased perfusion within cGM contralateral to the supratentorial lesion on the
      first postoperative study, and asymmetry was significant for both CBV (p = 0.008)
      and CBF (p < 0.01). For CBV, follow-up studies showed a significant trend towards
      recovery (p < 0.02). DTI changes were more pronounced in cWM. FA values suggested
      a "paradoxical" increase at initial follow-up, but steadily declined thereafter
      (p = 0.0003), without evidence of subsequent recovery. Diaschisis-related
      hemodynamic alterations within cGM appear on early postoperative studies, but CBV
      recovers over time. Conversely, cWM DTI changes are delayed and progressive.
      Although the clinical correlates of cCCD are yet to be elucidated, better
      understanding of longitudinal structural and hemodynamic changes within brain
      remote from the area of primary insult could have implications in research and
      clinical rehabilitative strategies. 

PMID- 24917519
TI  - Phylogenetic analysis and molecular signatures defining a monophyletic clade of
      heterocystous cyanobacteria and identifying its closest relatives.
AB  - Detailed phylogenetic and comparative genomic analyses are reported on 140 genome
      sequenced cyanobacteria with the main focus on the heterocyst-differentiating
      cyanobacteria. In a phylogenetic tree for cyanobacteria based upon concatenated
      sequences for 32 conserved proteins, the available cyanobacteria formed 8-9
      strongly supported clades at the highest level, which may correspond to the
      higher taxonomic clades of this phylum. One of these clades contained all
      heterocystous cyanobacteria; within this clade, the members exhibiting either
      true (Nostocales) or false (Stigonematales) branching of filaments were
      intermixed indicating that the division of the heterocysts-forming cyanobacteria
      into these two groups is not supported by phylogenetic considerations. However,
      in both the protein tree as well as in the 16S rRNA gene tree, the akinete
      forming heterocystous cyanobacteria formed a distinct clade. Within this clade,
      the members which differentiate into hormogonia or those which lack this ability
      were also separated into distinct groups. A novel molecular signature identified
      in this work that is uniquely shared by the akinete-forming heterocystous
      cyanobacteria provides further evidence that the members of this group are
      specifically related and they shared a common ancestor exclusive of the other
      cyanobacteria. Detailed comparative analyses on protein sequences from the
      genomes of heterocystous cyanobacteria reported here have also identified eight
      conserved signature indels (CSIs) in proteins involved in a broad range of
      functions, and three conserved signature proteins, that are either uniquely or
      mainly found in all heterocysts-forming cyanobacteria, but generally not found in
      other cyanobacteria. These molecular markers provide novel means for the
      identification of heterocystous cyanobacteria, and they provide evidence of their
      monophyletic origin. Additionally, this work has also identified seven CSIs in
      other proteins which in addition to the heterocystous cyanobacteria are uniquely
      shared by two smaller clades of cyanobacteria, which form the successive
      outgroups of the clade comprising of the heterocystous cyanobacteria in the
      protein trees. Based upon their close relationship to the heterocystous
      cyanobacteria, the members of these clades are indicated to be the closest
      relatives of the heterocysts-forming cyanobacteria. 

PMID- 24917520
TI  - Loss of expression of the tumour suppressor gene AIMP3 predicts survival
      following radiotherapy in muscle-invasive bladder cancer.
AB  - The aim of this study was to test the utility of AIMP3, an upstream regulator of
      DNA damage response following genotoxic stress, as a clinical biomarker in muscle
      invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a
      global gene-expression dataset. AIMP3 protein expression was determined by
      immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The
      mechanism of gene silencing was probed using methylation-specific PCR. The
      association between AIMP3 expression, Tp53 transactivity and genomic stability
      was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising
      radiation was demonstrated using immunofluorescence. Radiosensitisation effects
      of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs
      derived from patients enrolled in BCON, a Phase III multicentre radiotherapy
      trial in bladder cancer (ISRCTN45938399) were used to evaluate the association
      between AIMP3 expression and survival. The prognostic value of AIMP3 expression
      was determined in a TMA derived from patients treated by radical cystectomy. Loss
      of AIMP3 expression was frequent in MIBC and associated with impaired Tp53
      transactivity and genomic instability. AIMP3-knockdown was associated with an
      increase in radioresistance. Loss of AIMP3 expression was associated with
      survival in MIBC patients following radiotherapy (HR = 0.53; 95% CI: 0.36 to
      0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion,
      AIMP3 expression is lost in a subset of bladder cancers and is significantly
      predictive of survival following radiotherapy in MIBC patients. 

PMID- 24917521
TI  - One-step interfacial thiol-ene photopolymerization for metal nanoparticle
      decorated microcapsules (MNP@MCs).
AB  - We herein reported a one-step strategy to prepare the noble metal nanoparticle
      decorated microcapsules (MNP@MCs) through the interfacial thiol-ene
      photopolymerization. In the presence of amphiphlic polyhedral oligomeric
      silsesquioxane (POSS) containing thiol groups (PTPS) as a reactive surfactant and
      trimethylolpropane triacrylate (TMPTA) as a cross-linker, the oil phase of
      toluene dissolved with a photoinitiator was emulsified into a water phase
      containing a metal precursor to form an oil-in-water (O/W) emulsion. Upon
      irradiation of ultraviolet (UV) light, the thiol-ene photoploymerization and
      photoreduction at the interface of toluene/water lead to the formation of the
      cross-linked wall and metal nanoparticles, respectively. A series of gold,
      silver, and platinum nanoparticle-decorated microcapsules (AuNP@MC, AgNP@MC, and
      PtNP@MC) were prepared through this one-step interfacial thiol-ene
      photopolymerization and were characterized carefully by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and atomic force
      microscopy (AFM). The results revealed that the obtained MNP@MCs were 2.2-2.7 MUm
      in diameter with a wall of 40-70 nm in thickness, which was covered with the
      metal nanoparticles. The size and amount of metal nanoparticles increased with
      the increasing concentration of the metal precursor in water. Furthermore, the
      catalyst performance of AuNP@MC was studied by reduction of aromatic nitro
      compounds and exhibited the enhanced catalytic activity and good stability in the
      reduction of hydrophobic nitrophenol. It is believed that this robust,
      convenient, simple strategy based on the one-step interfacial thiol-ene
      photopolymerization will provide an important alternative to fabricate the
      functional metal nanoparticle-modified microcapsules. 

PMID- 24917522
TI  - Anti-diabetic effect of dietary mango (Mangifera indica L.) peel in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: In the present study, the composition of mango peel powder (MPP)
      collected from the mango pulp industry was determined and the effect of MPP on
      ameliorating diabetes and its associated complications was studied. RESULTS:
      Mango peel was rich in polyphenols, carotenoids and dietary fibre. Peel extract
      contained various bioactive compounds and was found to be rich in soluble dietary
      fibre. Peel extract exhibited antioxidant properties and protected against DNA
      damage. Therefore, the effect of peel on ameliorating diabetes was investigated
      in a rat model of diabetes. A significant increase in urine sugar, urine volume,
      fasting blood glucose, total cholesterol, triglycerides and low density
      lipoprotein, and decrease in high density lipoprotein were observed in the rats;
      however, these parameters were ameliorated in diabetic rats fed with diet
      supplemented with mango peel at 5% and 10% levels in basal diet. Treatment of
      diabetic rats with MPP increased antioxidant enzyme activities and decreased
      lipid peroxidation in plasma, kidney and liver compared to untreated diabetic
      rats. Glomerular filtration rate and microalbuminuria levels were ameliorated in
      MPP treated diabetic group. CONCLUSIONS: Mango peel, a by-product, can be used as
      an ingredient in functional and therapeutic foods.

PMID- 24917525
TI  - A demonstration of the similiarities and differences in bone marrow morphology
      with nontuberculous mycobacterial infections.

PMID- 24917523
TI  - Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic
      steatosis.
AB  - A sequence polymorphism (rs738409, I148M) in patatin-like phospholipid domain
      containing protein 3 (PNPLA3) is strongly associated with nonalcoholic fatty
      liver disease (NAFLD), but the mechanistic basis for this association remains
      enigmatic. Neither ablation nor overexpression of wild-type PNPLA3 affects liver
      fat content in mice, whereas hepatic overexpression of the human 148M transgene
      causes steatosis. To determine whether the 148M allele causes fat accumulation in
      the liver when expressed at physiological levels, we introduced a methionine
      codon at position 148 of the mouse Pnpla3 gene. Knockin mice had normal levels of
      hepatic fat on a chow diet, but when challenged with a high-sucrose diet their
      liver fat levels increased 2 to 3-fold compared to wild-type littermates without
      any associated changes in glucose homeostasis. The increased liver fat in the
      knockin mice was accompanied by a 40-fold increase in PNPLA3 on hepatic lipid
      droplets, with no increase in hepatic PNPLA3 messenger RNA (mRNA). Similar
      results were obtained when the catalytic dyad of PNPLA3 was inactivated by
      substituting the catalytic serine with alanine (S47A). CONCLUSION: These data
      provide the first direct evidence that physiological expression of PNPLA3 148M
      variant causes NAFLD, and that the accumulation of catalytically inactive PNPLA3
      on the surfaces of lipid droplets is associated with the accumulation of TG in
      the liver.

PMID- 24917524
TI  - Uveitis profile and treatment response in Iranian patients with sarcoidosis.
AB  - The aim of the study was to assess the clinical features and treatment responses
      in Iranian patients with sarcoid uveitis. A retrospective review of patients
      diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral
      clinic in Tehran, Iran. Demographic and clinical features of patients, treatment
      modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes
      from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean
      duration of follow-up was 44.7 +/- 45 months (range 3-175). Thirty-six eyes (54.5
      %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior
      uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical
      corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of
      uveitis. All of the patients finally responded to treatment in the form of
      inflammation reduction and/or vision improvement. The average time interval
      before initial clinical response following treatment was 3.2 +/- 3 months (range
      1-72). This study disclosed a higher predominance of females and intermediate
      form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory
      drugs combined with corticosteroids resulted in good visual outcome and control
      of uveitis with a possible fewer corticosteroid side effects.

PMID- 24917526
TI  - Imaging modalities for the in vivo surveillance of mesenchymal stromal cells.
AB  - Bone marrow stromal cells exist as mesenchymal stromal cells (MSCs) and have the
      capacity to differentiate into multiple tissue types when subjected to
      appropriate culture conditions. This property of MSCs creates therapeutic
      opportunities in regenerative medicine for the treatment of damage to neural,
      cardiac and musculoskeletal tissues or acute kidney injury. The prerequisite for
      successful cell therapy is delivery of cells to the target tissue. Assessment of
      therapeutic outcomes utilize traditional methods to examine cell function of MSC
      populations involving routine biochemical or histological analysis for cell
      proliferation, protein synthesis and gene expression. However, these methods do
      not provide sufficient spatial and temporal information. In vivo surveillance of
      MSC migration to the site of interest can be performed through a variety of
      imaging modalities such as the use of radiolabelling, fluc protein expression
      bioluminescence imaging and paramagnetic nanoparticle magnetic resonance imaging.
      This review will outline the current methods of in vivo surveillance of
      exogenously administered MSCs in regenerative medicine while addressing potential
      technological developments. Furthermore, nanoparticles and microparticles for
      cellular labelling have shown that migration of MSCs can be spatially and
      temporally monitored. In vivo surveillance therefore permits time-stratified
      assessment in animal models without disruption of the target organ. In vivo
      tracking of MSCs is non-invasive, repeatable and non-toxic. Despite the
      excitement that nanoparticles for tracking MSCs offer, delivery methods are
      difficult because of the challenges with imaging three-dimensional systems. The
      current advances and growth in MSC research, is likely to provide a wealth of
      evidence overcoming these issues.

PMID- 24917527
TI  - Evaluation of psychological guidance impact on complete denture wearer's
      satisfaction.
AB  - The purpose of this study was to evaluate the impact of psychological
      intervention on edentulous patients' satisfaction with complete clinically
      satisfactory complete dentures. The survey was conducted in China Medical
      University involving 84 individuals receiving complete dentures at this
      institution from August 2013 to March 2014. Participants were randomly allocated
      to intervention and control groups consisting of 42 subjects, respectively. In
      the intervention group, individuals received oral health education and
      psychological intervention before and after the whole process. In the control
      group, 42 cases received doctor's regular advice after treatment. Satisfaction
      regarding aesthetic, speech, mastication, retention and comfort was rated in the
      first and third month after prosthesis treatment. Patients overall aesthetic,
      speech, mastication and retention were significantly improved in both
      intervention and control groups in 3 months later after prosthesis treatment when
      compared with the first month (P < 0.05). No significant difference existed for
      comfort in control group. Patient scores on aesthetic, speech, mastication and
      retention at both first and third month evaluations (P < 0.05) differed between
      the control and intervention groups. However, there was no difference for their
      scores related to comfort (P > 0.05) in first and third month. The study
      concludes that psychological intervention plays a significant role in improving
      patient satisfaction with complete dentures. 

PMID- 24917528
TI  - Predicting the relative solubilities of racemic and enantiopure crystals by
      density-functional theory.
AB  - Isolation of chiral molecules as pure enantiomers remains a fundamental challenge
      in chemical research. Enantioselective enrichment through preferential
      crystallization is an efficient method to achieve enantiopure compounds, but its
      applicability depends on the relative stability of the enantiopure and racemic
      crystal forms. Using a simple thermodynamic model and first-principles density
      functional calculations, it is possible to predict the difference in solubility
      between the enantiopure and racemic solid phases. This approach uses dispersion
      corrected density functionals and is capable of accurately predicting the
      solution-phase entantiomeric excess to within about 10 % of experimental
      measurements on average. The accuracy of the exchange-hole dipole moment (XDM)
      model of dispersion enables the viability of the proposed method. 

PMID- 24917529
TI  - A simple and robust test object for the assessment of isotropic diffusion
      kurtosis.
AB  - PURPOSE: To create a robust test object for the assessment of isotropic diffusion
      kurtosis and to investigate the relationships between barrier concentration and
      kurtosis and diffusion coefficients. THEORY AND METHODS: Diffusion kurtosis
      imaging is an extension of conventional diffusion-weighted magnetic resonance
      imaging which provides a means of assessing the degree to which diffusion
      processes of spin-bearing particles are non-Gaussian, a property that is
      quantified by the kurtosis. We present a set of test objects, each possessing a
      different concentration of colloidal dispersion, allowing barrier concentration
      of the dispersed colloidal particles to be related to the kurtosis of the water
      diffusion. Diffusion coefficients from the kurtosis model and the monoexponential
      model are compared. RESULTS: A relationship between barrier concentration and
      kurtosis is found, demonstrating that the diffusion process becomes less Gaussian
      as the barrier concentration is increased. Differences in the two estimates for
      the diffusion coefficients are examined. The test object is robust, displaying
      long-term reproducibility of results. CONCLUSIONS: Colloidal dispersions provide
      a suitable and stable test object for the assessment and reproducibility
      measurements of kurtosis.

PMID- 24917530
TI  - Prediction of pediatric bipolar disorder using neuroanatomical signatures of the
      amygdala.
AB  - OBJECTIVES: Pediatric bipolar disorder is currently diagnosed based on signs and
      symptoms, and without objective diagnostic biomarkers. In the present study, we
      investigated the utility of structural neuroanatomical signatures of the amygdala
      to objectively differentiate individual subjects with pediatric bipolar disorder
      from matched healthy controls. METHODS: Structural T1 -weighted neuroimaging
      scans were obtained from 16 children and adolescents with unmedicated DSM-IV
      bipolar disorder (11 males, five females) and 16 matched healthy controls (11
      males, five females). Voxel-based gray matter morphometric features extracted
      from a bilateral region-of-interest within the amygdala were used to develop a
      multivariate pattern analysis model which was utilized in predicting novel or
      'unseen' individual subjects as either bipolar disorder or healthy controls.
      RESULTS: The model assigned 25 out of 32 subjects the correct label (bipolar
      disorder/healthy) translating to a 78.12% diagnostic accuracy, 81.25%
      sensitivity, 75.00% specificity, 76.47% positive predictive value, and 80.00%
      negative predictive value and an area under the receiver operating characteristic
      curve (ROC) of 0.81. The predictions were significant at p = 0.0014 (chi(2) test
      p-value). CONCLUSIONS: These results reaffirm previous reports on the existence
      of neuroanatomical abnormalities in the amygdala of pediatric patients with
      bipolar disorder. Remarkably, the present study also demonstrates that
      neuroanatomical signatures of the amygdala can predict individual subjects with
      bipolar disorder with a relatively high specificity and sensitivity. To the best
      of our knowledge, this is the first study to present a proof-of-concept
      diagnostic marker of pediatric bipolar disorder based on structural neuroimaging
      scans of largely medication-naive patients.

PMID- 24917531
TI  - Five-year follow up of a randomised controlled trial comparing subtotal with
      total abdominal hysterectomy.
AB  - OBJECTIVES: To compare the rates of urinary incontinence (UI) and other
      complications of subtotal abdominal hysterectomy (SAH) with total abdominal
      hysterectomy (TAH) at 5 years after surgery. DESIGN: Randomised clinical trial
      with central, computer-generated randomisation. SETTING: Danish multi-centre
      trial performed in 11 departments of gynaecology. POPULATION: Women referred with
      benign uterine diseases scheduled for abdominal hysterectomy. METHODS: Women were
      randomised to either SAH (n = 161) or TAH (n = 158). Follow-up data were
      collected from participants using postal questionnaires sent out 5 years after
      surgery. Complications of hysterectomy were further examined by scrutinising
      registered discharge summaries following hospitalisation. Intention-to-treat and
      per-protocol analyses were conducted. Potential bias caused by missing data was
      handled using multiple imputation. MAIN OUTCOME MEASURES: The primary outcome was
      UI. Secondary outcomes included constipation, prolapse of the vaginal vault or
      cervical stump, satisfaction with sexual life, pelvic pain, postoperative
      complications and vaginal bleeding. RESULTS: The response rate was 234/319
      (73.4%). A significantly higher proportion of respondents had urinary
      incontinence 5 years after SAH 34/113 (30.1%) than TAH 21/119 (17.6%) (RR 1.71,
      95% confidence interval 1.06-2.75, P = 0.026). This difference reduced after
      multiple imputation to account for missing data (RR 1.37, 95% confidence interval
      0.99-1.89, P = 0.052). Eleven of the 101 women (11%) in the SAH group still
      experienced vaginal bleeding. No other differences were found between the two
      types of abdominal hysterectomy. AUTHORS' CONCLUSIONS: A smaller proportion of
      women suffered from UI after TAH than after SAH 5 years postoperatively. Around
      one in ten women continued to experience vaginal bleeding 5 years after SAH.

PMID- 24917532
TI  - Origins and functional diversification of salinity-responsive Na(+) , K(+) ATPase
      alpha1 paralogs in salmonids.
AB  - The Salmoniform whole-genome duplication is hypothesized to have facilitated the
      evolution of anadromy, but little is known about the contribution of paralogs
      from this event to the physiological performance traits required for anadromy,
      such as salinity tolerance. Here, we determined when two candidate, salinity
      responsive paralogs of the Na(+) , K(+) ATPase alpha subunit (alpha1a and
      alpha1b) evolved and studied their evolutionary trajectories and tissue-specific
      expression patterns. We found that these paralogs arose during a small-scale
      duplication event prior to the Salmoniform, but after the teleost, whole-genome
      duplication. The 'freshwater paralog' (alpha1a) is primarily expressed in the
      gills of Salmoniformes and an unduplicated freshwater sister species (Esox
      lucius) and experienced positive selection in the freshwater ancestor of
      Salmoniformes and Esociformes. Contrary to our predictions, the 'saltwater
      paralog' (alpha1b), which is more widely expressed than alpha1a, did not
      experience positive selection during the evolution of anadromy in the Coregoninae
      and Salmonine. To determine whether parallel mutations in Na(+) , K(+) ATPase
      alpha1 may contribute to salinity tolerance in other fishes, we studied
      independently evolved salinity-responsive Na(+) , K(+) ATPase alpha1 paralogs in
      Anabas testudineus and Oreochromis mossambicus. We found that a quarter of the
      mutations occurring between salmonid alpha1a and alpha1b in functionally
      important sites also evolved in parallel in at least one of these species.
      Together, these data argue that paralogs contributing to salinity tolerance
      evolved prior to the Salmoniform whole-genome duplication and that strong
      selection and/or functional constraints have led to parallel evolution in
      salinity-responsive Na(+) , K(+) ATPase alpha1 paralogs in fishes. 

PMID- 24917533
TI  - The diagnostic accuracy of Clinical Dehydration Scale in identifying dehydration
      in children with acute gastroenteritis: a systematic review.
AB  - AIM: To systematically update diagnostic accuracy of the Clinical Dehydration
      Scale (CDS) in clinical recognition of dehydration in children with acute
      gastroenteritis. METHODS: Six databases were searched for diagnostic accuracy
      studies in which population were children aged 1 to 36 months with acute
      gastroenteritis; index test was the CDS; and reference test was post-illness
      weight gain. RESULTS: Three studies involving 360 children were included. Limited
      evidence showed that in high-income countries the CDS provides strong diagnostic
      accuracy for ruling in moderate and severe (>6%) dehydration (positive likelihood
      ratio 5.2-6.6), but has limited value for ruling it out (negative likelihood
      ratio 0.4-0.55). In low-income countries, the CDS has limited value either for
      ruling moderate or severe dehydration in or out. In both settings, the CDS had
      limited value for ruling in or out dehydration <3% or dehydration 3% to 6%.
      CONCLUSION: The CDS can help assess moderate to severe dehydration in high-income
      settings. Given the limited data, the evidence should be viewed with caution.

PMID- 24917534
TI  - An unusual cause of failure to thrive in an infant with vomiting and elevated
      transaminases.

PMID- 24917535
TI  - Severity of manifestations in tuberous sclerosis complex in relation to genotype.
AB  - OBJECTIVE: Patients with tuberous sclerosis complex (TSC) commonly present with
      significant neurologic deficits, including seizures, autism, and intellectual
      disability. Previous evidence suggests that the TSC2 mutation genotype may be
      associated with a more severe disease phenotype. This study evaluates the
      association of the TSC1 and TSC2 genotype with patient and disease
      characteristics in a retrospective review of a large TSC Natural History Database
      consisting of 919 patients with TSC. METHODS: Univariate logistic regression was
      conducted to evaluate the association of the TSC1 and TSC2 gene mutations with
      patient and disease characteristics. RESULTS: As compared to patients with the
      TSC1 mutation, patients with the TSC2 mutation were younger (p = 0.02), more
      likely to have partial epilepsy (odds ratio (OR) 1.74, p = 0.0015), complex
      partial seizures (OR 2.03, p = 0.02), infantile spasms (IS) (OR 1.67, p = 0.01),
      subependymal giant-cell astrocytomas (SEGAs) (OR 1.64, p = 0.01), and
      intellectual disability (OR 2.90, p = 0.0002). SIGNIFICANCE: The clinical
      presentation of TSC is highly variable and not well understood. Our findings
      confirm and supplement existing literature that TSC2 mutation is likely to be
      associated with a more severe, earlier presenting TSC phenotype, including
      infantile spasms.

PMID- 24917536
TI  - Trans-patella tendon approach for domed lateral unicompartmental knee
      arthroplasty does not increase the risk of patella tendon shortening.
AB  - PURPOSE: Shortening of the patella tendon has been noted after total knee
      arthroplasty and has been associated with diminished functional outcomes.
      Traumatic and/or ischaemic injury peri-operatively are suggested causes. The
      Oxford domed lateral unicompartmental knee arthroplasty (UKA) requires a vertical
      incision through the patella tendon to facilitate orientation of the proximal
      tibial saw cut; this may induce scarring or impair vascularity of the tendon and
      can cause shortening. This study investigated the hypothesis that the trans
      patella tendon incision increases the incidence of patella tendon shortening
      after domed lateral UKA when compared to flat lateral UKA performed without the
      trans-patella tendon incision. METHODS: The radiographs of 50 patients who
      underwent domed lateral UKA, using the trans-patella tendon approach, and a
      cohort of 30 patients who underwent flat lateral UKA, in which an incision
      through the patella tendon was not employed, were reviewed retrospectively. The
      patella tendon length (PTL) and the Insall-Salvati ratio were measured. In
      addition, pre-operative and post-operative clinical scores were recorded using
      both the OKS and AKSS. A change in PTL of greater than or equal to 10 % was
      considered to be significant. RESULTS: In the domed lateral UKA group, 13
      patients demonstrated a >10 % change in the PTL at 1-year post-surgery (2
      shortened and 11 lengthened). In the flat lateral UKA group, nine patients
      demonstrated a significant change in the PTL at 1-year post-surgery (2 shortened
      and 7 lengthened). CONCLUSION: This study demonstrated that using a trans-patella
      approach during lateral domed UKA surgery did not significantly increase patella
      tendon shortening and did not result in reduced clinical outcomes.

PMID- 24917537
TI  - Erratum to: Bankart repair versus Bankart repair plus remplissage: an in vitro
      biomechanical comparative study.

PMID- 24917538
TI  - Intraoperative ligament laxity influences functional outcome 1 year after total
      knee arthroplasty.
AB  - PURPOSE: To find out if there is an association between ligament laxity measured
      intraoperatively and functional outcome 1 year after total knee arthroplasty
      (TKA). METHODS: Medial and lateral ligament laxities were measured
      intraoperatively in extension and in 90 degrees  of flexion in 108 patients [122
      knees; median age 70 (range 42-83) years]. Mechanical axes were measured
      preoperatively and at 1-year follow-up. Outcome measures were the Knee Injury and
      Osteoarthritis Outcome Score (KOOS), the Knee Society Clinical Rating System, the
      Oxford Knee Score and patient satisfaction. The relationships between laxity and
      outcome scores were examined by median regression analyses. RESULTS: Post
      operative mechanical axis had a significant effect on the association between
      ligament laxity and KOOS. Therefore, the material was stratified on post
      operative mechanical axis. In perfectly aligned and valgus-aligned TKAs, there
      was a negative correlation between medial laxity and all subscores in KOOS. The
      most important regression coefficient (beta) was recorded for the effect of
      medial laxity in extension on activities of daily living (ADLs) (beta = -7.32, p
      < 0.001), sport/recreation (beta = -6.9, p = 0.017) and pain (beta = -5.9, p =
      0.006), and for the effect of medial laxity in flexion on ADLs (beta = -3.11, p =
      0.023) and sport/recreation (beta = -4.18, p = 0.042). CONCLUSIONS: In order to
      improve the functional results after TKA, orthopaedic surgeons should monitor
      ligament laxity and mechanical axis intraoperatively and avoid medial laxity more
      than 2 mm in extension and 3 mm in flexion in neutral and valgus-aligned knees.
      LEVEL OF EVIDENCE: II.

PMID- 24917540
TI  - Overview of the enhanced natural gestures instructional approach and illustration
      of its use with three students with Angelman syndrome.
AB  - BACKGROUND: This investigation details procedures used to teach enhanced natural
      gestures (ENGs) and illustrates its use with three students with Angelman
      syndrome (AS). MATERIALS AND METHODS: Themes were extracted, using a process of
      content analysis, to organize individuals' feedback pertaining to previous
      versions of the instructional programme. A 'B' case study design was then
      employed to follow administration of the modified programme with three students
      in Madrid, Spain. Programme impact was examined relative to changes in each
      student's uses of ENGs spontaneously and in response to non-specific verbal
      prompts, along with team members' responses to a questionnaire designed to
      evaluate programme efficacy. RESULTS: Two of the three students demonstrated
      particularly rapid and spontaneous uses of their ENGs. Both quantitative and
      qualitative feedback from teams supported programme efficacy for all three
      students. CONCLUSIONS: The approach appears viable for individuals with AS and
      has implications for individuals presenting other diagnoses as well. Additional
      educational/clinical and research implications are discussed.

PMID- 24917539
TI  - Reliability of dynamic balance simultaneously with cognitive performance in
      patients with ACL deficiency and after ACL reconstructions and in healthy
      controls.
AB  - PURPOSE: To determine the intra- and inter-session reliability of balance and
      cognitive performance in anterior cruciate ligament-deficient (ACLD) and ACL
      reconstructed (ACLR) and matched athletes. METHODS: Using SMART EquiTest,
      recovery reactions of the groups were assessed during single-leg standing,
      following medium and large forward perturbations with and without performing a
      cognitive (Stroop) task. The outcomes included reaction time (RT), latency and
      amplitude for balance and error ratio (ER) and RT for cognitive performance. The
      participants of each group repeated the tests 2-7 days after the first session.
      Intraclass correlation coefficient (ICC) and standard error of measurement were
      computed in order to assess relative and absolute reliability, respectively.
      RESULTS: Single- and dual-task balance measures had moderate to very high
      reliability in ACLD (ICC = 0.63-0.88), ACLR (ICC = 0.62-0.93) and control (ICC =
      0.69-0.98) athletes. The ICCs for RT of Stroop were between 0.87 and 0.90 in
      ACLD, between 0.70 and 0.74 in ACLR and between 0.66 and 0.70 in controls and for
      ER of Stroop were between 0.36 and 0.90 in ACLD, between 0.42 and 0.49 in ACLR
      and between 0.41 and 0.51 in controls. CONCLUSIONS: Balance measures and RT of
      the cognitive task in single- and dual-task conditions have acceptable
      reliability and may be incorporated into the evaluation of physical and mental
      function of athletes following ACL injury and reconstruction. ER of the cognitive
      task is less reliable which needs to be considered in future research. LEVEL OF
      EVIDENCE: Prognostic study, case-control, Level III.

PMID- 24917541
TI  - A novel method for gathering and prioritizing disease candidate genes based on
      construction of a set of disease-related MeSH(r) terms.
AB  - BACKGROUND: Understanding the molecular mechanisms involved in disease is
      critical for the development of more effective and individualized strategies for
      prevention and treatment. The amount of disease-related literature, including new
      genetic information on the molecular mechanisms of disease, is rapidly
      increasing. Extracting beneficial information from literature can be facilitated
      by computational methods such as the knowledge-discovery approach. Several
      methods for mining gene-disease relationships using computational methods have
      been developed, however, there has been a lack of research evaluating specific
      disease candidate genes. RESULTS: We present a novel method for gathering and
      prioritizing specific disease candidate genes. Our approach involved the
      construction of a set of Medical Subject Headings (MeSH) terms for the effective
      retrieval of publications related to a disease candidate gene. Information
      regarding the relationships between genes and publications was obtained from the
      gene2pubmed database. The set of genes was prioritized using a "weighted
      literature score" based on the number of publications and weighted by the number
      of genes occurring in a publication. Using our method for the disease states of
      pain and Alzheimer's disease, a total of 1101 pain candidate genes and 2810
      Alzheimer's disease candidate genes were gathered and prioritized. The precision
      was 0.30 and the recall was 0.89 in the case study of pain. The precision was
      0.04 and the recall was 0.6 in the case study of Alzheimer's disease. The
      precision-recall curve indicated that the performance of our method was superior
      to that of other publicly available tools. CONCLUSIONS: Our method, which
      involved the use of a set of MeSH terms related to disease candidate genes and a
      novel weighted literature score, improved the accuracy of gathering and
      prioritizing candidate genes by focusing on a specific disease.

PMID- 24917542
TI  - Characterization of RO5126946, a Novel alpha7 nicotinic acetylcholine receptor
      positive allosteric modulator.
AB  - Both preclinical evidence and clinical evidence suggest that alpha7 nicotinic
      acetylcholine receptor activation (alpha7nAChR) improves cognitive function, the
      decline of which is associated with conditions such as Alzheimer's disease and
      schizophrenia. Moreover, allosteric modulation of alpha7nAChR is an emerging
      therapeutic strategy in an attempt to avoid the rapid desensitization properties
      associated with the alpha7nAChR after orthosteric activation. We used a calcium
      assay to screen for positive allosteric modulators (PAMs) of alpha7nAChR and
      report on the pharmacologic characterization of the novel compound RO5126946 (5
      chloro-N-[(1S,3R)-2,2-dimethyl-3-(4-sulfamoyl-phenyl)-cyclopropyl]-2-methoxy
      benzamide), which allosterically modulates alpha7nAChR activity. RO5126946
      increased acetylcholine-evoked peak current and delayed current decay but did not
      affect the recovery of alpha7nAChRs from desensitization. In addition,
      RO5126946's effects were absent when nicotine-evoked currents were completely
      blocked by coapplication of the alpha7nAChR-selective antagonist methyl
      lycaconitine. RO5126946 enhanced alpha7nAChR synaptic transmission and positively
      modulated GABAergic responses. The absence of RO5126946 effects at human
      alpha4beta2nAChR and 5-hydroxytryptamine 3 receptors, among others, indicated
      selectivity for alpha7nAChRs. In vivo, RO5126946 is orally bioavailable and brain
      penetrant and improves associative learning in a scopolamine-induced deficit
      model of fear conditioning in rats. In addition, procognitive effects of
      RO5126946 were investigated in the presence of nicotine to address potential
      pharmacologic interactions on behavior. RO5126946 potentiated nicotine's effects
      on fear memory when both compounds were administered at subthreshold doses and
      did not interfere with procognitive effects observed when both compounds were
      administered at effective doses. Overall, RO5126946 is a novel alpha7nAChR PAM
      with cognitive-enhancing properties. 

PMID- 24917543
TI  - Different contributions of dopamine D1 and D2 receptor activity to alcohol
      potentiation of brain stimulation reward in C57BL/6J and DBA/2J mice.
AB  - C57BL/6J (C57) and DBA/2J (DBA) mice respond differently to drugs that affect
      dopamine systems, including alcohol. The current study compared effects of D1 and
      D2 receptor agonists and antagonists, and the interaction between D1/D2
      antagonists and alcohol, on intracranial self-stimulation in male C57 and DBA
      mice to determine the role of dopamine receptors in the effects of alcohol on
      brain stimulation reward (BSR). In the initial strain comparison, dose effects on
      BSR thresholds and maximum operant response rates were determined for the D1
      receptor agonist SKF-82958 (+/--6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine; 0.1-0.56 mg/kg) and antagonist SCH 23390 (+-7-chloro
      8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinehydrochloride;
      0.003-0.056 mg/kg), and the D2 receptor agonist quinpirole (0.1-3.0 mg/kg) and
      antagonist raclopride (0.01-0.56 mg/kg). For the alcohol interaction, SCH 23390
      (0.003 mg/kg) or raclopride (0.03 mg/kg) was given before alcohol (0.6-2.4 g/kg
      p.o.). D1 antagonism dose-dependently elevated and SKF-82958 dose-dependently
      lowered BSR threshold in both strains; DBA mice were more sensitive to SKF-82958
      effects. D2 antagonism dose-dependently elevated BSR threshold only in C57 mice.
      Low doses of quinpirole elevated BSR threshold equally in both strains, whereas
      higher doses of quinpirole lowered BSR threshold only in C57 mice. SCH 23390, but
      not raclopride, prevented lowering of BSR threshold by alcohol in DBA mice.
      Conversely, raclopride, but not SCH 23390, prevented alcohol potentiation of BSR
      in C57 mice. These results extend C57 and DBA strain differences to D1/D2
      sensitivity of BSR, and suggest differential involvement of D1 and D2 receptors
      in the acute rewarding effects of alcohol in these two mouse strains. 

PMID- 24917544
TI  - Differential substitution for the discriminative stimulus effects of 3,4
      methylenedioxymethamphetamine and methylphenidate in rats.
AB  - Previous studies have demonstrated that methylphenidate, MDMA (3,4
      methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like
      subjective effects in humans. Furthermore, MDMA and methylphenidate substitute
      for the discriminative stimulus effects of psychostimulants, such as amphetamine
      and cocaine, in animals, which suggests that MDMA and methylphenidate may produce
      similar discriminative stimulus effects in rats. However, there is no evidence
      regarding the similarities between the discriminative stimulus effects of MDMA
      and methylphenidate. To explore this issue, cross-substitution, substitution, and
      combination tests were conducted in rats that had been trained to discriminate
      between MDMA (2.5 mg/kg) or methylphenidate (5.0 mg/kg) and saline. In the cross
      substitution tests, MDMA and methylphenidate did not cross-substitute for each
      other. In the substitution test, methamphetamine substituted for the
      discriminative stimulus effects of methylphenidate, but not for those of MDMA.
      Furthermore, ephedrine and bupropion, which activate dopaminergic and
      noradrenergic systems, substituted for the discriminative stimulus effects of
      methylphenidate. On the other hand, serotonin (5-HT) receptor agonists 5-HT1A and
      5-HT2 fully substituted for the discriminative stimulus effects of MDMA. These
      results suggest that activation of the noradrenergic and dopaminergic systems is
      important for the discriminative stimulus effects of methylphenidate, whereas
      activation of the serotonergic system is crucial for the discriminative stimulus
      effects of MDMA. Even though MDMA, like psychostimulants, exerts stimulant-like
      effects, our findings clearly indicate that the discriminative stimulus effects
      of MDMA are distinctly different from those of other psychostimulants in rats. 

PMID- 24917545
TI  - Antiallergic and antiasthmatic effects of a novel enhydrazinone ester (CEE-1):
      inhibition of activation of both mast cells and eosinophils.
AB  - Activation of mast cells and eosinophils is a fundamental process in the
      pathophysiology of allergic diseases. We have previously reported that the novel
      enhydrazinone ester CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1
      oate) possesses potent anti-inflammatory activity. We have now tested whether the
      compound also possesses antiallergic and antiasthmatic effects in vitro and in
      vivo. The compound significantly inhibited degranulation and leukotriene C4
      (LTC4) release from activated human eosinophils, as well as IgE-dependent
      degranulation and LTC4 release from passively sensitized rat basophilic leukemia
      cells and bone marrow-derived mouse mast cells. In human eosinophils, the drug
      was more potent in inhibiting degranulation than LTC4 release {IC50 = 0.4 MUM
      [confidence interval (CI): 0.1-0.9] versus 3.8 MUM (CI: 0.9-8.3)}, whereas in
      mast cells the reverse was essentially the case. The drug did not affect stimulus
      induced calcium transients in eosinophils but significantly inhibited early
      phosphorylation of extracellular signal-regulated kinases 1/2 and p38-mitogen
      activated protein kinases (MAPK). In vivo, topical application of 4.5-15 mg/kg of
      the compound significantly inhibited allergen-induced passive cutaneous
      anaphylaxis in mice. Similarly, in the mouse asthma model, the intranasal
      administration of 6.5-12.5 mg/kg of the compound significantly inhibited
      bronchial inflammation and eosinophil accumulation in bronchial lavage fluid, as
      well as abolishing airway hyper-responsiveness to methacholine. These results
      show that CEE-1 inhibits the activation of both mast cells and eosinophils in
      vitro, probably by blocking MAPK-activation pathways, and that these effects are
      translated into antiallergic and antiasthmatic effects in vivo. The compound,
      therefore, has potential application in the treatment of asthma and other
      allergic diseases. 

PMID- 24917546
TI  - Pharmacologic profile of the Adnectin BMS-962476, a small protein biologic
      alternative to PCSK9 antibodies for low-density lipoprotein lowering.
AB  - Proprotein convertase subtilisin kexin-9 (PCSK9) is an important pharmacological
      target for decreasing low-density lipoprotein (LDL) in cardiovascular disease,
      although seemingly inaccessible to small molecule approaches. Compared with
      therapeutic IgG antibodies currently in development, targeting circulating PCSK9
      with smaller molecular scaffolds could offer different profiles and reduced dose
      burdens. This inspired genesis of PCSK9-binding Adnectins, a protein family
      derived from human fibronectin-10th-type III-domain and engineered for high
      affinity target binding. BMS-962476, an ~11-kDa polypeptide conjugated to
      polyethylene glycol to enhance pharmacokinetics, binds with subnanomolar affinity
      to human. The X-ray cocrystal structure of PCSK9 with a progenitor Adnectin shows
      ~910 A(2) of PCSK9 surface covered next to the LDL receptor binding site, largely
      by residues of a single loop of the Adnectin. In hypercholesterolemic,
      overexpressing human PCSK9 transgenic mice, BMS-962476 rapidly lowered
      cholesterol and free PCSK9 levels. In genomic transgenic mice, BMS-962476
      potently reduced free human PCSK9 (ED50 ~0.01 mg/kg) followed by ~2-fold
      increases in total PCSK9 before return to baseline. Treatment of cynomolgus
      monkeys with BMS-962476 rapidly suppressed free PCSK9 >99% and LDL-cholesterol
      ~55% with subsequent 6-fold increase in total PCSK9, suggesting reduced clearance
      of circulating complex. Liver sterol response genes were consequently
      downregulated, following which LDL and total PCSK9 returned to baseline. These
      studies highlight the rapid dynamics of PCSK9 control over LDL and liver
      cholesterol metabolism and characterize BMS-962476 as a potent and efficacious
      PCSK9 inhibitor. 

PMID- 24917547
TI  - Prediction and modeling of effects on the QTc interval for clinical safety margin
      assessment, based on single-ascending-dose study data with AZD3839.
AB  - Corrected QT interval (QTc) prolongation in humans is usually predictable based
      on results from preclinical findings. This study confirms the signal from
      preclinical cardiac repolarization models (human ether-a-go-go-related gene,
      guinea pig monophasic action potential, and dog telemetry) on the clinical
      effects on the QTc interval. A thorough QT/QTc study is generally required for
      bioavailable pharmaceutical compounds to determine whether or not a drug shows a
      QTc effect above a threshold of regulatory interest. However, as demonstrated in
      this AZD3839 [(S)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5
      yl)phenyl)-1H-isoindol-3-amine hemifumarate] single-ascending-dose (SAD) study,
      high-resolution digital electrocardiogram data, in combination with adequate
      efficacy biomarker and pharmacokinetic data and nonlinear mixed effects modeling,
      can provide the basis to safely explore the margins to allow for robust modeling
      of clinical effect versus the electrophysiological risk marker. We also conclude
      that a carefully conducted SAD study may provide reliable data for effective
      early strategic decision making ahead of the thorough QT/QTc study. 

PMID- 24917548
TI  - A modified panel of sentinel congenital anomalies for potential use in mutation
      epidemiology based on birth defects registry data.
AB  - Since 1983, several authors have used panels of "sentinel" congenital anomalies
      that might serve as indicators of the human genome mutation rate. The current
      study suggests a considerably updated panel, and applies it to public health
      birth defects registry data to determine the potential number of de novo cases.
      Data were taken from deliveries in 1999-2009 from the Texas Birth Defects
      Registry, an active surveillance program. Cases with one of the conditions or
      syndromes in the panel were identified using codes and text searches. Frequencies
      and birth prevalence were calculated for the overall panel and subcategories
      within it. Of the 60 conditions appearing in previous papers on sentinel
      phenotypes, 21 (35%) were used in the current study along with 27 new phenotypes.
      We found 1,694 cases. Of those, 1,100 exhibited phenotypes thought to arise de
      novo in at least 90% of the cases ("all/almost all" subpanel), and 594 considered
      de novo in roughly 50-90% of cases ("most" subpanel). Chromosomal deletion
      disorders were present in 523 cases and imprinting disorders in 243. After
      adjusting for maternal age, occurrence of cases in the total panel, "most"
      subpanel, and imprinting disorders subpanel were significantly associated with
      paternal age. Our panel of sentinel phenotypes differs from previous panels due
      to evolved knowledge of genetic disorders, different approaches with respect to
      interviewing, and different operational definitions. It is hoped that using an
      overall panel as well as subpanels may maximize statistical power as well as
      suggest potential mechanisms.

PMID- 24917549
TI  - Hereditary vitamin D-resistant rickets presenting as alopecia.
AB  - Hereditary vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive
      disorder caused by mutations in the vitamin D receptor (VDR) gene. We report the
      case of an infant presenting with alopecia, growth failure, and gross motor
      developmental delay. Serum biochemistry and skeletal survey were consistent with
      rickets. After a poor response to standard treatment, genetic testing confirmed a
      c.147-2A>T novel mutation in the VDR gene consistent with HVDRR. It is important
      for dermatologists and pediatricians to recognize alopecia as a presenting sign
      of HVDRR because appropriate treatment leads to better growth and development of
      the child. 

PMID- 24917551
TI  - Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice
      with non-alcoholic steatohepatitis.
AB  - OBJECTIVE: No therapy for non-alcoholic steatohepatitis (NASH) has been approved
      so far. Roux-en-y gastric bypass (RYGB) is emerging as a therapeutic option,
      although its effect on NASH and related hepatic molecular pathways is unclear
      from human studies. We studied the effect of RYGB on pre-existent NASH and
      hepatic mitochondrial dysfunction-a key player in NASH pathogenesis-in a novel
      diet-induced mouse model nicely mimicking human disease. DESIGN: C57BL/6J mice
      were fed a high-fat high-sucrose diet (HF-HSD). RESULTS: HF-HSD led to early
      obesity, insulin resistance and hypercholesterolaemia. HF-HSD consistently
      induced NASH (steatosis, hepatocyte ballooning and inflammation) with fibrosis
      already after 12-week feeding. NASH was accompanied by hepatic mitochondrial
      dysfunction, characterised by decreased mitochondrial respiratory chain (MRC)
      complex I and IV activity, ATP depletion, ultrastructural abnormalities, together
      with higher 4-hydroxynonenal (HNE) levels, increased uncoupling protein 2 (UCP2)
      and tumour necrosis factor-alpha (TNF-alpha) mRNA and free cholesterol
      accumulation. In our model of NASH and acquired mitochondrial dysfunction, RYGB
      induced sustained weight loss, improved insulin resistance and inhibited
      progression of NASH, with a marked reversal of fibrosis. In parallel, RYGB
      preserved hepatic MRC complex I activity, restored ATP levels, limited HNE
      production and decreased TNF-alpha mRNA. CONCLUSIONS: Progression of NASH and
      NASH-related hepatic mitochondrial dysfunction can be prevented by RYGB. RYGB
      preserves respiratory chain complex activity, thereby restoring energy output,
      probably by limiting the amount of oxidative stress and TNF-alpha. These data
      suggest that modulation of hepatic mitochondrial function contributes to the
      favourable effect of RYBG on established NASH.

PMID- 24917552
TI  - Induced hydraulic pumping via integrated submicrometer cylindrical glass
      capillaries.
AB  - Here, we report on a micropump that generates hydraulic pressure owing to a
      mismatch in EOF rates of microchannels and submicrometer cylindrical glass
      capillaries integrated on silicon. The electrical conductance of such capillaries
      in the dilute limit departs from bulk linear behavior as well as from the surface
      charge-governed saturation in nanoslits that is well described by the assumption
      of a constant surface charge density. The capillaries show rather a gradual
      decrease in conduction at low salt concentrations, which can be explained more
      aptly by a variable surface charge density that accounts for chemical equilibrium
      of the surface. The micropump uses a traditional cross-junction structure with
      ten identical capillaries integrated in parallel on a side arm and each with a
      750 nm diameter and 3 mm length. For an applied voltage of 700 V, a hydraulic
      pressure up to 5 kPa is generated with a corresponding flow velocity nearly 3
      mm/s in a straight field-free branch 20 MUm wide, 10 MUm deep, and 10 mm long.
      The micropump utility has been demonstrated in an open tubular LC of three
      fluorescently labeled amino acids in just less than 20 s with minimal plate
      height values between 3 and 7 MUm. The submicrometer capillaries are self
      enclosed and produced through a unique process that does not require high
      resolution advanced lithography or wafer-bonding techniques to define their
      highly controlled precise structures. 

PMID- 24917553
TI  - Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and
      stiffness of aortic endothelial cells.
AB  - Endothelial cells (ECs) lining blood vessels express many mechanosensors,
      including platelet endothelial cell adhesion molecule-1 (PECAM-1), that convert
      mechanical force into biochemical signals. While it is accepted that mechanical
      stresses and the mechanical properties of ECs regulate vessel health, the
      relationship between force and biological response remains elusive. Here we show
      that ECs integrate mechanical forces and extracellular matrix (ECM) cues to
      modulate their own mechanical properties. We demonstrate that the ECM influences
      EC response to tension on PECAM-1. ECs adherent on collagen display divergent
      stiffening and focal adhesion growth compared with ECs on fibronectin. This is
      because of protein kinase A (PKA)-dependent serine phosphorylation and
      inactivation of RhoA. PKA signalling regulates focal adhesion dynamics and EC
      compliance in response to shear stress in vitro and in vivo. Our study identifies
      an ECM-specific, mechanosensitive signalling pathway that regulates EC compliance
      and may serve as an atheroprotective mechanism that maintains blood vessel
      integrity in vivo. 

PMID- 24917554
TI  - Antiangiogenic activity of trabectedin in myxoid liposarcoma: involvement of host
      TIMP-1 and TIMP-2 and tumor thrombospondin-1.
AB  - Trabectedin is a marine natural product, approved in Europe for the treatment of
      soft tissue sarcoma and relapsed ovarian cancer. Clinical and experimental
      evidence indicates that trabectedin is particularly effective against myxoid
      liposarcomas where response is associated to regression of capillary networks.
      Here, we investigated the mechanism of the antiangiogenic activity of trabectedin
      in myxoid liposarcomas. Trabectedin directly targeted endothelial cells,
      impairing functions relying on extracellular matrix remodeling (invasion and
      branching morphogenesis) through the upregulation of the inhibitors of matrix
      metalloproteinases TIMP-1 and TIMP-2. Increased TIMPs synthesis by the tumor
      microenvironment following trabectedin treatment was confirmed in xenograft
      models of myxoid liposarcoma. In addition, trabectedin upregulated tumor cell
      expression of the endogenous inhibitor thrombospondin-1 (TSP-1, a key regulator
      of angiogenesis-dependent dormancy in sarcoma), in in vivo models of myxoid
      liposarcomas, in vitro cell lines and primary cell cultures from patients' myxoid
      liposarcomas. Chromatin Immunoprecipitation analysis showed that trabectedin
      displaced the master regulator of adipogenesis C/EBPbeta from the TSP-1 promoter,
      indicating an association between the up-regulation of TSP-1 and induction of
      adipocytic differentiation program by trabectedin. We conclude that trabectedin
      inhibits angiogenesis through multiple mechanisms, including directly affecting
      endothelial cells in the tumor microenvironment--with a potentially widespread
      activity--and targeting tumor cells' angiogenic activity, linked to a tumor
      specific molecular alteration.

PMID- 24917557
TI  - Acute anti-hyperglycaemic effects of an unripe apple preparation containing
      phlorizin in healthy volunteers: a preliminary study.
AB  - BACKGROUND: The health-promoting properties of apples are directly related to the
      biologically active compounds that they contain, such as polyphenols. The
      objective of this study was to prepare a low-sugar, fibre- and phlorizin-enriched
      powder from unripe apples and to gain insight regarding its anti-hyperglycaemic
      activity in healthy volunteers. RESULTS: The unripe apples (Malus domestica
      Borkh.) were collected 30 days after the full bloom day; blanched and pressed to
      obtain apple pomace which was then processed with a food cutter, oven-dried and
      milled to prepare apple powder. The concentrations of total sugars, water-soluble
      pectin and phlorizin in the apple preparation were 153.44 +/- 2.46, 27.73 +/-
      0.51 and 12.61 +/- 0.15 g kg(-1), respectively. Acute ingestion of the apple
      preparation improved glucose metabolism in the oral glucose tolerance test (OGTT)
      in six healthy volunteers by reducing the postprandial glucose response at 15 to
      30 min by approximately two-fold (P < 0.05) and by increasing urinary glucose
      excretion during the 2- to 4-h interval of the OGTT by five-fold (P < 0.05).
      CONCLUSION: The results obtained indicate that the dried and powdered pomace of
      unripe apples can be used as a health-promoting natural product for the reduction
      of postprandial glycaemia and to improve the health of patients with diabetes.

PMID- 24917550
TI  - Diagnosis and management of adult coeliac disease: guidelines from the British
      Society of Gastroenterology.
AB  - A multidisciplinary panel of 18 physicians and 3 non-physicians from eight
      countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA)
      reviewed the literature on diagnosis and management of adult coeliac disease
      (CD). This paper presents the recommendations of the British Society of
      Gastroenterology. Areas of controversies were explored through phone meetings and
      web surveys. Nine working groups examined the following areas of CD diagnosis and
      management: classification of CD; genetics and immunology; diagnostics; serology
      and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies;
      quality of life; novel treatments; patient support; and screening for CD. 

PMID- 24917559
TI  - Graphene nanomaterials as biocompatible and conductive scaffolds for stem cells:
      impact for tissue engineering and regenerative medicine.
AB  - The discovery of the interesting intrinsic properties of graphene, a two
      dimensional nanomaterial, has boosted further research and development for
      various types of applications from electronics to biomedicine. During the last
      decade, graphene and several graphene-derived materials, such as graphene oxide,
      carbon nanotubes, activated charcoal composite, fluorinated graphenes and three
      dimensional graphene foams, have been extensively explored as components of
      biosensors or theranostics, or to remotely control cell-substrate interfaces,
      because of their remarkable electro-conductivity. To date, despite the intensive
      progress in human stem cell research, only a few attempts to use carbon
      nanotechnology in the stem cell field have been reported. Interestingly, most of
      the recent in vitro studies indicate that graphene-based nanomaterials (i.e.
      mainly graphene, graphene oxide and carbon nanotubes) promote stem cell adhesion,
      growth, expansion and differentiation. Although cell viability in vitro is not
      affected, their potential nanocytoxicity (i.e. nanocompatibility and consequences
      of uncontrolled nanobiodegradability) in a clinical setting using humans remains
      unknown. Therefore, rigorous internationally standardized clinical studies in
      humans that would aim to assess their nanotoxicology are requested. In this paper
      we report and discuss the recent and pertinent findings about graphene and
      derivatives as valuable nanomaterials for stem cell research (i.e. culture,
      maintenance and differentiation) and tissue engineering, as well as for
      regenerative, translational and personalized medicine (e.g. bone reconstruction,
      neural regeneration). Also, from scarce nanotoxicological data, we also highlight
      the importance of functionalizing graphene-based nanomaterials to minimize the
      cytotoxic effects, as well as other critical safety parameters that remain
      important to take into consideration when developing nanobionanomaterials.

PMID- 24917558
TI  - Vasodilator-stimulated phosphoprotein promotes activation of hepatic stellate
      cells by regulating Rab11-dependent plasma membrane targeting of transforming
      growth factor beta receptors.
AB  - Liver microenvironment is a critical determinant for development and progression
      of liver metastasis. Under transforming growth factor beta (TGF-beta)
      stimulation, hepatic stellate cells (HSCs), which are liver-specific pericytes,
      transdifferentiate into tumor-associated myofibroblasts that promote tumor
      implantation (TI) and growth in the liver. However, the regulation of this HSC
      activation process remains poorly understood. In this study, we tested whether
      vasodilator-stimulated phosphoprotein (VASP) of HSCs regulated the TGF-beta
      mediated HSC activation process and tumor growth. In both an experimental liver
      metastasis mouse model and cancer patients, colorectal cancer cells reaching
      liver sinusoids induced up-regulation of VASP and alpha-smooth muscle actin
      (alpha-SMA) in adjacent HSCs. VASP knockdown in HSCs inhibited TGF-beta-mediated
      myofibroblastic activation of HSCs, TI, and growth in mice. Mechanistically, VASP
      formed protein complexes with TGF-beta receptor II (TbetaRII) and Rab11, a Ras
      like small GTPase and key regulator of recycling endosomes. VASP knockdown
      impaired Rab11 activity and Rab11-dependent targeting of TbetaRII to the plasma
      membrane, thereby desensitizing HSCs to TGF-beta1 stimulation. CONCLUSIONS: Our
      study demonstrates a requirement of VASP for TGF-beta-mediated HSC activation in
      the tumor microenvironment by regulating Rab11-dependent recycling of TbetaRII to
      the plasma membrane. VASP and its effector, Rab11, in the tumor microenvironment
      thus present therapeutic targets for reducing TI and metastatic growth in the
      liver.

PMID- 24917560
TI  - Chemical kinetic resolution of unprotected beta-substituted beta-amino acids
      using recyclable chiral ligands.
AB  - The first chemical method for resolution of N,C-unprotected beta-amino acids was
      developed through enantioselective formation and disassembly of nickel(II)
      complexes under operationally convenient conditions. The specially designed
      chiral ligands are inexpensive and can be quantitatively recycled along with
      isolation of the target beta-substituted-beta-amino acids in good yields and
      excellent enantioselectivity. The method features a broad synthetic generality
      including beta-aryl, beta-heteroaryl, and beta-alkyl-derived beta-amino acids.
      The procedure is easily scaled up, and was used for the synthetically and
      economically advanced preparation of the anti-diabetic drug sitagliptin. 

PMID- 24917561
TI  - In sickness and in health: the role of TRAPP and associated proteins in disease.
AB  - Transport protein particle (TRAPP) represents a series of related protein
      complexes that function in specific stages of inter-organelle traffic. They share
      a core of subunits that can activate the GTPase Rab1 through a guanine nucleotide
      exchange factor (GEF) activity and are distinguished by 'accessory' subunits
      giving each complex its distinct function. The subunits are ubiquitously
      expressed and, thus, mutations in TRAPP subunits would be expected to be
      embryonic lethal. However, since its discovery, a number of subunits have been
      found to be mutated in several diverse human disorders suggesting that some of
      these subunits may have cell- or tissue-specific functions. Here we review the
      current state of knowledge with respect to TRAPP subunit mutations in human
      disease. We suggest ideas to explain their tissue-specific phenotypes and present
      avenues for future investigation.

PMID- 24917562
TI  - Electrophysiological and morphological maturation of murine fetal cardiomyocytes
      during electrical stimulation in vitro.
AB  - The aim of this study was to investigate whether continuous electrical
      stimulation affects electrophysiological properties and cell morphology of fetal
      cardiomyocytes (FCMs) in culture. Fetal cardiomyocytes at day 14.5 post coitum
      were harvested from murine hearts and electrically stimulated for 6 days in
      culture using a custom-made stimulation chamber. Subsequently, action potentials
      of FCM were recorded with glass microelectrodes. Immunostainings of alpha
      Actinin, connexin 43, and vinculin were performed. Expression of ion channel
      subunits Kcnd2, Slc8a1, Cacna1, Kcnh2, and Kcnb1 was analyzed by quantitative
      reverse-transcriptase polymerase chain reaction. Action potential duration to 50%
      and 90% repolarization (APD50 and APD90) of electrically stimulated FCMs were
      significantly decreased when compared to nonstimulated control FCM. Alignment of
      cells was significantly higher in stimulated FCM when compared to control FCM.
      The expression of connexin 43 was significantly increased in stimulated FCM when
      compared to control FCM. The ratio between cell length and cell width of the
      stimulated FCM was significantly higher than in control FCM. Kcnh2 and Kcnd2 were
      upregulated in stimulated FCM when compared to control FCM. Expression of Slc8a1,
      Cacna1c, and Kcnb1 was not different in stimulated and control FCMs. The decrease
      in APD50 observed after electrical stimulation of FCM in vitro corresponds to the
      electrophysiological maturation of FCM in vivo. Expression levels of ion channels
      suggest that some important but not all aspects of the complex process of
      electrophysiological maturation are promoted by electrical stimulation. Parallel
      alignment, increased connexin 43 expression, and elongation of FCM are signs of a
      morphological maturation induced by electrical stimulation. 

PMID- 24917563
TI  - Work factors are associated with workplace activity limitations in systemic lupus
      erythematosus.
AB  - OBJECTIVE: The objective of this study was to examine the extent of workplace
      activity limitations among persons with lupus and to identify factors associated
      with activity limitations among those employed. METHODS: We conducted a cross
      sectional study using a mailed survey and clinical data of persons with lupus who
      attended a large lupus outpatient clinic. Data were collected on demographics,
      health, work factors and psychosocial measures. The workplace activity
      limitations scale (WALS) was used to measure difficulty related to different
      activities at work. Multivariable analysis examined the association of health,
      work context, psychosocial and demographic variables with workplace activity
      limitations. RESULTS: We received 362 responses from 604 (60%) mailed surveys.
      Among those not employed, 52% reported not working because of lupus. A range of
      physical and mental tasks were reported as difficult. Each of the physical,
      cognitive and energy work activities was cited as difficult by more than one
      third of participants. Among employed participants, 40% had medium to high WALS
      difficulty scores. In the multivariable analysis, factors significantly
      associated with workplace activity limitations were older age, greater disease
      activity, fatigue, poorer health status measured by the 36-item Short Form Health
      Survey, lower job control, greater job strain and working more than 40 h/week.
      CONCLUSION: People with lupus experience limitations and difficulty at work.
      Determinants of workplace activity limitations are mainly those related to
      workplace and health factors.

PMID- 24917564
TI  - Impaired endothelial function in patients with undifferentiated connective tissue
      disease: a follow-up study.
AB  - OBJECTIVE: In this study the alteration of endothelial function, arterial
      stiffness and autoantibodies was investigated in patients with UCTD. METHODS:
      Thirty-one patients with UCTD were included in this prospective study. All the
      patients remained in the UCTD stage during the average 3.8 years follow-up
      period. The onset of UCTD was denoted as UCTD1, while the end of the follow-up
      period was called UCTD2. Flow-mediated vasodilation (FMD), carotid intima-media
      thickness (IMT), autoantibodies [such as anti-SSA, anti-SSB, anti-DNA, anti-RNP,
      anti-CCP, aCL, anti-oxidized low-density lipoprotein (oxLDL) and AECA], von
      Willebrand factor antigen, thrombomodulin (TM), endothelin 1 (ET-1) and lipid
      parameters were measured. RESULTS: In the UCTD1 stage, high-sensitivity CRP
      (hsCRP) and endothelial cell activation and/or damage markers such as TM, ET-1
      and AECA levels were significantly higher compared with controls (controls vs
      UCTD1: hsCRP, P < 0.0001; TM, P = 0.001; ET-1, P < 0.0001). In the UCTD2 stage,
      the carotid IMT increased (UCTD1 vs UCTD2, P = 0.01) and FMD further deteriorated
      (UCTD1 and UCTD2, P = 0.001). In UCTD2 there was a close correlation between the
      carotid IMT, and duration of the disease (r = 0.612, P < 0.001), the level of TM
      (r = 0.673, P < 0.001) and anti-oxLDL (r = 0.800, P < 0.001). CONCLUSION: Our
      data suggest that the presence of inflammation and autoantibodies provoke
      endothelial cell activation and/or injury in UCTD patients. The persistent
      endothelial dysfunction may provoke the development of atherosclerosis. FMD was
      found to be the most sensitive marker for arterial stiffness, and the increase of
      IMT clearly indicated the existence of preclinical atherosclerosis in UCTD
      patients.

PMID- 24917565
TI  - Long-term follow-up results of primary and recurrent pigmented villonodular
      synovitis.
AB  - OBJECTIVE: Adequate documentation of the outcome of treatment of pigmented
      villonodular synovitis (PVNS) is sparse. Available case series show relatively
      short follow-up times and often combine locations or subtypes to increase patient
      numbers. This article describes the long-term follow-up of a single institution's
      large consecutive series of PVNS. METHODS: Retrospectively, 107 PVNS patients
      were identified between 1985 and 2011 by searching pathology and radiology
      records. Treatment complications, recurrences and quality of life were evaluated.
      Most patients (85.2%) were primarily or secondarily treated at our institution.
      RESULTS: Both subtypes, localized PVNS [29 (27%)] and diffuse PVNS [75 (70%)]
      were represented. The knee was affected in 88% of patients. Treatments received
      were surgery, external beam radiotherapy, radiosynovectomy, targeted therapy,
      immunotherapy or combinations of these. Forty-nine (46%) patients had prior
      treatment elsewhere. The mean follow-up from diagnosis until last contact was 7.0
      years (range 0.3-27.4) for localized PVNS and 14.5 years (range 1.1-48.7) for
      diffuse PVNS. The 1- and 5-year recurrence-free survival rates for diffuse PVNS
      were 69% and 32%, respectively. Quality of life, estimated by 36-item Short Form
      Health Survey (SF-36) scores, were not significantly different between localized
      and diffuse PVNS. However, both patient groups scored lower than the general
      population norms on the general health component (59.2 and 56.3, respectively, P
      < 0.05). CONCLUSION: Recurrence rates of PVNS increase with time. Long-term
      follow-up shows, particularly in diffuse PVNS, it is a continually recurring
      problem, and over time it becomes increasingly difficult to cure. The quality of
      life is decreased in patients with PVNS compared with the general population.

PMID- 24917566
TI  - The cross-sectional association between uric acid and atherosclerosis and the
      role of low-grade inflammation: the CODAM study.
AB  - OBJECTIVES: The aims of this study were to investigate (i) associations between
      uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure
      index (AAIx) and carotid intima-media thickness (CIMT) in the total population
      and in predefined subgroups according to glucose metabolism status and (ii) the
      extent to which these associations are explained by low-grade inflammation.
      METHODS: Cross-sectional analyses were conducted among 530 individuals [60.6%
      men, mean age 58.9 years (s.d. 6.9), 52.6% normal glucose metabolism (NGM)] at
      increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht
      study. A low-grade inflammation score was computed by averaging the z-scores of
      eight inflammation markers [CRP, TNF-alpha, IL-6, IL-8, serum amyloid A,
      intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin].
      RESULTS: After adjustment for traditional CVD risk factors, plasma uric acid (per
      s.d. of 81 MUmol/l) was associated with CVD in individuals with NGM [odds ratio
      (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM)
      (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated
      with CIMT in the total population (beta = 0.024, 95% CI 0.007, 0.042) and
      slightly more strongly in individuals with NGM (beta = 0.030, 95% CI 0.006,
      0.054) than DGM (beta = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443).
      There was no association between uric acid and AAIx in any group (P interaction =
      0.058). Uric acid was associated with low-grade inflammation in the total
      population (beta = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low
      grade inflammation to the models did not attenuate any of the associations.
      CONCLUSION: The associations for uric acid with CIMT, and with CVD in NGM only,
      were not explained by low-grade inflammation. A difference in the strength of the
      associations between individuals with NGM and DGM was suggested.

PMID- 24917568
TI  - Geographic and socioeconomic variations in adolescent toothbrushing: a multilevel
      cross-sectional study of 15 year olds in Scotland.
AB  - BACKGROUND: This study examined urban-rural and socioeconomic differences in
      adolescent toothbrushing. METHODS: The data were modelled using logistic
      multilevel modelling and the Markov Chain Monte Carlo method of estimation. Twice
      a-day toothbrushing was regressed upon age, family affluence, family structure,
      school type, area-level deprivation and rurality, for boys and girls separately.
      RESULTS: Boys' toothbrushing was associated with area-level deprivation but not
      rurality. Variance at the school level remained significant in the final model
      for boys' toothbrushing. The association between toothbrushing and area-level
      deprivation was particularly strong for girls, after adjustment for individuals'
      family affluence and type of school attended. Rurality too was independently
      significant with lower odds of brushing teeth in accessible rural areas.
      CONCLUSION: The findings are at odds with the results of a previous study which
      showed lower caries prevalence among children living in rural Scotland. A further
      study concluded that adolescents have a better diet in rural Scotland. In total,
      these studies highlight the need for an examination into the relative importance
      of diet and oral health on caries, as increases are observed in population
      obesity and consumption of sugars.

PMID- 24917570
TI  - Chronic spontaneous idiopathic spleen hematoma presenting as a large cystic
      tumor: a case report with review of the literature.
AB  - Spontaneous idiopathic splenic hematomas occur very rare. Hematomas of the spleen
      are usually associated with trauma, or infectious, neoplastic, or hematologic
      diseases. They present a diagnostic challenge as they can be easily confused with
      other more common entities. We report a case of atraumatic idiopathic splenic
      hematoma in a patient with no underlying systemic or local disease and discuss
      the approach to diagnosis and treatment. 

PMID- 24917571
TI  - Multi-scale analysis of simulated proton and alpha irradiation.
AB  - This article presents the results of the simulated irradiation with protons and
      alpha particles of two different geometrical models, representing a cell nucleus
      and its chromatin content. The characteristics of the energy deposition are
      studied at both micrometric and nanometric length scales. In particular, the
      stochastic distributions of the quantities associated with the total energy
      deposit in the micrometric volume are derived and compared with the physical
      characteristics of the clusters of energy deposits. An innovative multi-scale
      correlation method is introduced and tested against the simulations' data. This
      new approach links the two relevant length scales exploiting the differences in
      the kinetic energy spectra of the secondary electrons produced by the primary
      particles. The characteristics of the energy deposition of the electrons in the
      chosen material are determined in the first instance. Few free parameters of the
      model, linking the electrons energy deposits with the total energy deposit of the
      primary particles, can be used for summarising the characteristic of the
      irradiation with the chosen radiation quality at the two different length scales.

PMID- 24917569
TI  - Iridium-catalyzed enantioselective allylic substitution of unstabilized enolates
      derived from alpha,beta-unsaturated ketones.
AB  - We report Ir-catalyzed, enantioselective allylic substitution reactions of
      unstabilized silyl enolates derived from alpha,beta-unsaturated ketones.
      Asymmetric allylic substitution of a variety of allylic carbonates with silyl
      enolates gave allylated products in 62-94% yield with 90-98% ee and >20:1
      branched-to-linear selectivity. The synthetic utility of this method was
      illustrated by the short synthesis of an anticancer agent, TEI-9826.

PMID- 24917567
TI  - Toward male individualization with rapidly mutating y-chromosomal short tandem
      repeats.
AB  - Relevant for various areas of human genetics, Y-chromosomal short tandem repeats
      (Y-STRs) are commonly used for testing close paternal relationships among
      individuals and populations, and for male lineage identification. However, even
      the widely used 17-loci Yfiler set cannot resolve individuals and populations
      completely. Here, 52 centers generated quality-controlled data of 13 rapidly
      mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide
      populations. Strikingly, >99% of the 12,272 unrelated males were completely
      individualized. Haplotype diversity was extremely high (global: 0.9999985,
      regional: 0.99836-0.9999988). Haplotype sharing between populations was almost
      absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within
      populations was generally rare (0.8% nonunique haplotypes), significantly lower
      in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%).
      Analysis of molecular variance revealed 99.98% of variation within populations,
      0.018% among populations within groups, and 0.002% among groups. Of the 2,372
      newly and 156 previously typed male relative pairs, 29% were differentiated
      including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype
      diversity was increased in 86% of the populations tested and overall male
      relative differentiation was raised by 23.5%. Our study demonstrates the value of
      RM Y-STRs in identifying and separating unrelated and related males and provides
      a reference database. 

PMID- 24917572
TI  - The modified unified interaction model: incorporation of dose-dependent localised
      recombination.
AB  - The unified interaction model (UNIM) was developed to simulate thermoluminescence
      (TL) linear/supralinear dose-response and the dependence of the supralinearity on
      ionisation density, i.e. particle type and energy. Before the development of the
      UNIM, this behaviour had eluded all types of TL modelling including conduction
      band/valence band (CB/VB) kinetic models. The dependence of the supralinearity on
      photon energy was explained in the UNIM as due to the increasing role of geminate
      (localised recombination) with decreasing photon/electron energy. Recently, the
      Ben Gurion University group has incorporated the concept of trapping
      centre/luminescent centre (TC/LC) spatially correlated complexes and
      localised/delocalised recombination into the CB/VB kinetic modelling of the
      LiF:Mg,Ti system. Track structure considerations are used to describe the
      relative population of the TC/LC complexes by an electron-hole or by an electron
      only as a function of both photon/electron energy and dose. The latter dependence
      was not included in the original UNIM formulation, a significant over
      simplification that is herein corrected. The modified version, the M-UNIM, is
      then applied to the simulation of the linear/supralinear dose-response
      characteristics of composite peak 5 in the TL glow curve of LiF:Mg,Ti at two
      representative average photon/electron energies of 500 and 8 keV. 

PMID- 24917573
TI  - Free fatty acid uptake in humans with CD36 deficiency.
AB  - Animal models have demonstrated that CD36 facilitates cell membrane free fatty
      acid (FFA) transport, but its role in human metabolism is not well understood. We
      measured heart, liver, adipose (three depots), and muscle (truncal postural and
      thigh locomotive) FFA uptake using [(11)C]palmitate positron emission tomography
      (PET) scans in a family of five carrying the Pro90Ser CD36 mutation (2
      homozygotes had no CD36) and matched control volunteers. PET scans were done
      under conditions of suppressed and slightly increased palmitate concentrations.
      During suppressed palmitate conditions, muscle and adipose palmitate uptake were
      markedly reduced in homozygotes but not heterozygotes for the Pro90Ser CD36
      mutation, whereas when palmitate concentration was slightly increased, uptake in
      muscle and adipose did not differ between control subjects and homozygous family
      members. Hepatic FFA uptake was similar in all participants regardless of
      palmitate concentrations, whereas myocardial FFA uptake was diminished in the
      Pro90Ser homozygotes during both suppressed and increased palmitate conditions.
      We conclude that CD36 1) facilitates FFA transport into muscle and adipose tissue
      in humans when extracellular concentrations are reduced but not when they are
      modestly elevated, 2) is not rate limiting for hepatic FFA uptake, and 3) is
      needed for normal cardiac FFA uptake over a range of FFA concentrations from low
      to slightly elevated. 

PMID- 24917574
TI  - Nucleotides released from palmitate-challenged muscle cells through pannexin-3
      attract monocytes.
AB  - Obesity-associated low-grade inflammation in metabolically relevant tissues
      contributes to insulin resistance. We recently reported monocyte/macrophage
      infiltration in mouse and human skeletal muscles. However, the molecular triggers
      of this infiltration are unknown, and the role of muscle cells in this context is
      poorly understood. Animal studies are not amenable to the specific investigation
      of this vectorial cellular communication. Using cell cultures, we investigated
      the crosstalk between myotubes and monocytes exposed to physiological levels of
      saturated and unsaturated fatty acids. Media from L6 myotubes treated with
      palmitate-but not palmitoleate-induced THP1 monocyte migration across transwells.
      Palmitate activated the Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF
      kappaB) pathway in myotubes and elevated cytokine expression, but the monocyte
      chemoattracting agent was not a polypeptide. Instead, nucleotide degradation
      eliminated the chemoattracting properties of the myotube-conditioned media.
      Moreover, palmitate-induced expression and activity of pannexin-3 channels in
      myotubes were mediated by TLR4-NF-kappaB, and TLR4-NF-kappaB inhibition or
      pannexin-3 knockdown prevented monocyte chemoattraction. In mice, the expression
      of pannexin channels increased in adipose tissue and skeletal muscle in response
      to high-fat feeding. These findings identify pannexins as new targets of
      saturated fatty acid-induced inflammation in myotubes, and point to nucleotides
      as possible mediators of immune cell chemoattraction toward muscle in the context
      of obesity. 

PMID- 24917575
TI  - Tissue-specific differences in the development of insulin resistance in a mouse
      model for type 1 diabetes.
AB  - Although insulin resistance is known to underlie type 2 diabetes, its role in the
      development of type 1 diabetes has been gaining increasing interest. In a model
      of type 1 diabetes, the nonobese diabetic (NOD) mouse, we found that insulin
      resistance driven by lipid- and glucose-independent mechanisms is already present
      in the liver of prediabetic mice. Hepatic insulin resistance is associated with a
      transient rise in mitochondrial respiration followed by increased production of
      lipid peroxides and c-Jun N-terminal kinase activity. At the onset of diabetes,
      increased adipose tissue lipolysis promotes myocellular diacylglycerol
      accumulation. This is paralleled by increased myocellular protein kinase C theta
      activity and serum fetuin A levels. Muscle mitochondrial oxidative capacity is
      unchanged at the onset but decreases at later stages of diabetes. In conclusion,
      hepatic and muscle insulin resistance manifest at different stages and involve
      distinct cellular mechanisms during the development of diabetes in the NOD mouse.

PMID- 24917576
TI  - Type 1 diabetes in NOD mice unaffected by mast cell deficiency.
AB  - Mast cells have been invoked as important players in immune responses associated
      with autoimmune diseases. Based on in vitro studies, or in vivo through the use
      of Kit mutant mice, mast cells have been suggested to play immunological roles in
      direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation
      of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2
      polarization, all of which could significantly impact the immune response against
      self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now,
      the role of mast cells in the onset and incidence of T1D has only been indirectly
      tested through the use of low-specificity mast cell inhibitors and activators,
      and published studies reported contrasting results. Our three laboratories have
      generated independently two strains of mast cell-deficient nonobese diabetic
      (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and
      Boston), to address the effects of mast cell deficiency on the development of T1D
      in the NOD strain. Our collective data demonstrate that both incidence and
      progression of T1D in NOD mice are independent of mast cells. Moreover, analysis
      of pancreatic lymph node cells indicated that lack of mast cells has no
      discernible effect on the autoimmune response, which involves both innate and
      adaptive immune components. Our results demonstrate that mast cells are not
      involved in T1D in the NOD strain, making their role in this process nonessential
      and excluding them as potential therapeutic targets. 

PMID- 24917577
TI  - Fluvastatin causes NLRP3 inflammasome-mediated adipose insulin resistance.
AB  - Statins reduce lipid levels and are widely prescribed. Statins have been
      associated with an increased incidence of type 2 diabetes, but the mechanisms are
      unclear. Activation of the NOD-like receptor family, pyrin domain containing 3
      (NLRP3)/caspase-1 inflammasome, promotes insulin resistance, a precursor of type
      2 diabetes. We showed that four different statins increased interleukin-1beta (IL
      1beta) secretion from macrophages, which is characteristic of NLRP3 inflammasome
      activation. This effect was dose dependent, absent in NLRP3(-/-) mice, and
      prevented by caspase-1 inhibition or the diabetes drug glyburide. Long-term
      fluvastatin treatment of obese mice impaired insulin-stimulated glucose uptake in
      adipose tissue. Fluvastatin-induced activation of the NLRP3/caspase-1 pathway was
      required for the development of insulin resistance in adipose tissue explants, an
      effect also prevented by glyburide. Fluvastatin impaired insulin signaling in
      lipopolysaccharide-primed 3T3-L1 adipocytes, an effect associated with increased
      caspase-1 activity, but not IL-1beta secretion. Our results define an
      NLRP3/caspase-1-mediated mechanism of statin-induced insulin resistance in
      adipose tissue and adipocytes, which may be a contributing factor to statin
      induced development of type 2 diabetes. These results warrant scrutiny of insulin
      sensitivity during statin use and suggest that combination therapies with
      glyburide, or other inhibitors of the NLRP3 inflammasome, may be effective in
      preventing the adverse effects of statins. 

PMID- 24917578
TI  - GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through
      hypothalamic AMPK.
AB  - GLP-1 receptor (GLP-1R) is widely located throughout the brain, but the precise
      molecular mechanisms mediating the actions of GLP-1 and its long-acting analogs
      on adipose tissue as well as the brain areas responsible for these interactions
      remain largely unknown. We found that central injection of a clinically used GLP
      1R agonist, liraglutide, in mice stimulates brown adipose tissue (BAT)
      thermogenesis and adipocyte browning independent of nutrient intake. The
      mechanism controlling these actions is located in the hypothalamic ventromedial
      nucleus (VMH), and the activation of AMPK in this area is sufficient to blunt
      both central liraglutide-induced thermogenesis and adipocyte browning. The
      decreased body weight caused by the central injection of liraglutide in other
      hypothalamic sites was sufficiently explained by the suppression of food intake.
      In a longitudinal study involving obese type 2 diabetic patients treated for 1
      year with GLP-1R agonists, both exenatide and liraglutide increased energy
      expenditure. Although the results do not exclude the possibility that
      extrahypothalamic areas are also modulating the effects of GLP-1R agonists, the
      data indicate that long-acting GLP-1R agonists influence body weight by
      regulating either food intake or energy expenditure through various hypothalamic
      sites and that these mechanisms might be clinically relevant. 

PMID- 24917579
TI  - Antimicrobial activity of ceftolozane/tazobactam tested against Pseudomonas
      aeruginosa and Enterobacteriaceae with various resistance patterns isolated in
      European hospitals (2011-12).
AB  - OBJECTIVES: To evaluate the in vitro activity of ceftolozane/tazobactam and
      comparator agents tested against contemporary Gram-negative bacteria.
      Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well
      established beta-lactamase inhibitor. METHODS: A total of 10 532 Gram-negative
      organisms (2191 Pseudomonas aeruginosa and 8341 Enterobacteriaceae) were
      consecutively collected from 31 medical centres located in 13 European countries
      plus Turkey and Israel. The organisms were tested for susceptibility by broth
      microdilution methods as described by the CLSI M07-A9 document and the results
      interpreted according to EUCAST as well as CLSI breakpoint criteria. Selected
      ceftazidime- and/or meropenem-resistant P. aeruginosa isolates were screened for
      the presence of beta-lactamase genes by PCR. RESULTS: P. aeruginosa exhibited
      high rates of multidrug-resistant (31.9%) and extensively drug-resistant (24.6%)
      isolates and 11.6% of isolates were susceptible only to colistin. When tested
      against P. aeruginosa, ceftolozane/tazobactam (MIC(50), 1 mg/L) was generally 4
      fold more active than ceftazidime (MIC(50), 4 mg/L) and inhibited >90% of
      isolates with an MIC of <=8 mg/L in nine countries. In contrast, the highest
      susceptibility rates observed for ceftazidime and meropenem, respectively, were
      86.0%/86.0% (UK) and 85.2%/86.1% (Ireland) (67.2%/67.1% overall).
      Ceftolozane/tazobactam (MIC(50/90), 0.25/2 mg/L; 93.7% and 95.2% inhibited at <=4
      and <=8 mg/L, respectively), meropenem [MIC(50/90), <=0.06/<=0.06 mg/L; 98.0%
      susceptible (EUCAST)] and tigecycline [MIC(50/90), 0.12/1 mg/L; 94.1% susceptible
      (EUCAST)] were the most active compounds tested against Enterobacteriaceae.
      CONCLUSIONS: Ceftolozane/tazobactam was the most active beta-lactam agent tested
      against P. aeruginosa and demonstrated higher in vitro activity than currently
      available cephalosporins and piperacillin/tazobactam when tested against
      Enterobacteriaceae.

PMID- 24917580
TI  - Population pharmacokinetics and dosing simulations of cefuroxime in critically
      ill patients: non-standard dosing approaches are required to achieve therapeutic
      exposures.
AB  - OBJECTIVES: To investigate the population pharmacokinetics of cefuroxime in
      critically ill patients. METHODS: In this observational pharmacokinetic study,
      multiple blood samples were taken over one dosing interval of intravenous
      cefuroxime. Blood samples were analysed using a validated ultra HPLC tandem mass
      spectrometry technique. Population pharmacokinetic analysis and dosing
      simulations were performed using non-linear mixed-effects modelling. RESULTS: One
      hundred and sixty blood samples were collected from 20 patients. CL(CR) ranged
      between 10 and 304 mL/min. A two-compartment model with between-subject
      variability on CL, V of the central compartment and V of the peripheral
      compartment described the data adequately. Twenty-four hour urinary CL(CR) was
      supported as a descriptor of drug CL. The population model for CL was CL =
      theta(1) * CL(CR)/100, where theta(1) is the typical cefuroxime CL in the
      population, which is 9.0 L/h. The mean V was 22.5 L. Dosing simulations showed
      failure to achieve the pharmacokinetic/pharmacodynamic target of 65% fT(>MIC) for
      an MIC of 8 mg/L with standard dosing regimens for patients with CL(CR) >=50
      mL/min. CONCLUSIONS: Administration of standard doses by intermittent bolus is
      likely to result in underdosing for many critically ill patients. Continuous
      infusion of higher than normal doses after a loading dose is more likely to
      achieve pharmacokinetic/pharmacodynamic targets. However, even continuous
      infusion of high doses (up to 9 g per day) does not guarantee adequate levels for
      all patients with a CL(CR) of >=300 mL/min if the MIC is 8 mg/L.

PMID- 24917581
TI  - Resistance to third-generation cephalosporins in Acinetobacter baumannii due to
      horizontal transfer of a chromosomal segment containing ISAba1-ampC.

PMID- 24917582
TI  - Mechanisms of reduced susceptibility and genotypic prediction of antibiotic
      resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients.
AB  - OBJECTIVES: To investigate mechanisms of reduced susceptibility to commonly used
      antibiotics in Prevotella cultured from patients with cystic fibrosis (CF),
      patients with invasive infection and healthy control subjects and to determine
      whether genotype can be used to predict phenotypic resistance. METHODS: The
      susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with
      detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within
      the CfxA-type beta-lactamase and expression of efflux pumps. RESULTS: Prevotella
      isolates positive for a cfxA-type gene had higher MICs of amoxicillin and
      ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation
      within the CfxA-type beta-lactamase (Y239D) was associated with ceftazidime
      resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold
      more likely to harbour ermF compared with the US CF, UK invasive and UK healthy
      control isolates, respectively. Higher concentrations of azithromycin (P < 0.001)
      and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF
      positive isolates compared with ermF-negative isolates. Furthermore, tetQ
      positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and
      doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp.
      were also shown, for the first time, to express resistance nodulation division
      (RND)-type efflux pumps. CONCLUSIONS: This study has demonstrated that Prevotella
      isolated from various sources harbour a common pool of resistance genes and
      possess RND-type efflux pumps, which may contribute to tetracycline resistance.
      The findings indicate that antibiotic resistance is common in Prevotella spp.,
      but the genotypic traits investigated do not reflect phenotypic antibiotic
      resistance in every instance.

PMID- 24917584
TI  - In vitro activity of mecillinam against Enterobacteriaceae with NDM-1
      carbapenemase.

PMID- 24917583
TI  - Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir,
      but fails to restore activity of the HIV integrase enzyme and viral replication
      capacity.
AB  - BACKGROUND: The results of several clinical trials suggest that the integrase
      inhibitor dolutegravir may be less prone than other drugs to the emergence of HIV
      drug resistance mutations in treatment-naive patients. We have shown that the
      R263K mutation commonly emerged during tissue culture selection studies with
      dolutegravir and conferred low levels of resistance to this drug while
      simultaneously diminishing both HIV replication capacity and integrase enzymatic
      activity. E138K has been identified as a secondary mutation for dolutegravir in
      selection studies and has also been observed as a secondary mutation in the
      clinic for the integrase inhibitors raltegravir and elvitegravir. METHODS: We
      used biochemical cell-free strand-transfer assays and tissue culture assays to
      characterize the effects of the E138K/R263K combination of mutations on
      resistance to dolutegravir, integrase enzyme activity and HIV-1 replication
      capacity. RESULTS: We show here that the addition of the E138K substitution to
      R263K increased the resistance of HIV-1 to dolutegravir but failed to restore
      viral replication capacity, integrase strand-transfer activity and integration
      within cellular DNA. We also show that the addition of E138K to R263K did not
      increase the resistance to raltegravir or elvitegravir. The addition of the E138K
      substitution to R263K was also less detrimental to integrase strand-transfer
      activity and integration than a different secondary mutation at position H51Y
      that had also been selected in culture. CONCLUSIONS: The E138K substitution
      failed to restore the defect in viral replication capacity that is associated
      with R263K, confirming previous selection studies that failed to identify
      compensatory mutation(s) for the latter primary mutation. This study suggests
      that the R263K resistance pathway may represent an evolutionary dead end for HIV
      in treatment-naive individuals who are treated with dolutegravir and will need to
      be confirmed by the long-term use of dolutegravir in the clinic.

PMID- 24917586
TI  - Pedometer-facilitated walking intervention shows promising effectiveness for
      reducing cancer fatigue: a pilot randomized trial.
AB  - OBJECTIVE: Mechanisms for cancer related fatigue suggest that exercise but "not
      too much and not too little" could be effective. This study aimed to investigate
      feasibility and estimate the potential effects of a walking exercise program in
      people with advanced cancer and fatigue. DESIGN: A pilot randomized trial.
      SETTING: McGill University Health Centre (MUHC), Montreal, Canada. SUBJECTS:
      People with advanced cancer undergoing interdisciplinary assessment and
      rehabilitation with a fatigue level of 4 to 10 on a visual analogue scale.
      INTERVENTIONS: An 8-week fatigue-adapted, walking intervention, facilitated using
      a pedometer (STEPS), and offered at the same time as or after rehabilitation.
      MEASURES: Measures of fatigue, physical function and well-being were administered
      at entry, and 8, 16 and 24 weeks. Generalized estimating equations (GEE)
      estimated the odds of response for people receiving the STEPS program in
      comparison to the odds of response in the controls (odds ratio, OR). RESULTS:
      Twenty-six persons were randomized to three groups: during rehabilitation, after
      rehabilitation, and usual care. For the fatigue measures the OR for STEPS offered
      at any time using an intention-to-treat approach was 3.68 (95%CI: 1.05-12.88);
      for the physical function measures, the OR was 1.40 (95%CI: 0.41- 4.79) and 2.36
      (95%CI: 0.66-8.51) for the well-being measures. CONCLUSION: Fifty percent of
      eligible people were able to participate. This small trial suggests that a
      personalized exercise program reduces fatigue and that 100 people are needed in a
      full strength trial.

PMID- 24917585
TI  - A potential role for human UDP-glucuronosyltransferase 1A4 promoter single
      nucleotide polymorphisms in the pharmacogenomics of tamoxifen and its
      derivatives.
AB  - Tamoxifen (Tam) is a selective estrogen receptor modulator used to inhibit breast
      tumor growth. Tam can be directly N-glucuronidated via the tertiary amine group
      or O-glucuronidated after cytochrome P450-mediated hydroxylation. In this study,
      the glucuronidation of Tam and its hydroxylated and/or chlorinated derivatives [4
      hydroxytamoxifen (4OHTam), toremifene (Tor), and 4-hydroxytoremifene (4OHTor)]
      was examined using recombinant human UDP-glucuronosyltransferases (UGTs) from the
      1A subfamily and human hepatic microsomes. Recombinant UGT1A4 catalyzed the
      formation of N-glucuronides of Tam and its derivatives and was the most active
      UGT enzyme toward these compounds. Therefore, it was hypothesized that single
      nucleotide polymorphisms (SNPs) in the promoter region of UGT1A4 have the ability
      to significantly decrease the glucuronidation rates of Tam metabolites in the
      human liver. In vitro activity of 64 genotyped human liver microsomes was used to
      determine the association between the UGT1A4 promoter and coding region SNPs and
      the glucuronidation rates of Tam, 4OHTam, Tor, and 4OHTor. Significant decreases
      in enzymatic activity were observed in microsomes for individuals heterozygous
      for -163G/A and -217T/G. These alterations in glucuronidation may lead to
      prolonged circulating half-lives and may potentially modify the effectiveness of
      these drugs in the treatment of breast cancer. 

PMID- 24917587
TI  - The ambiguity of the concept of participation in measurement instruments:
      operationalization of participation influences research outcomes.
AB  - OBJECTIVE: This study explores, based on the International Classification of
      Functioning, Disability and Health, the consequences of different
      operationalizations of participation in regression models predicting
      participation in one sample of patients. DESIGN: Cross-sectional, comparative
      study. SETTING: Department of Neurology of a University Hospital. SUBJECTS: A
      total of 677 patients with a Neuromuscular Disease. MEASURES: Participation was
      measured using the Neuromuscular Disease Impact Profile questionnaire, the RAND
      36 Item Health Survey (social functioning, role limitations-physical, role
      limitations-emotional) and the Impact on Participation and Autonomy questionnaire
      (autonomy outdoors, social relations). Potential predictors of participation
      included type of neuromuscular disease, body functions (measured with
      Neuromuscular Disease Impact Profile), activities (measured with Neuromuscular
      Disease Impact Profile), environmental factors (measured with Neuromuscular
      Disease Impact Profile), and personal factors (measured with the 13-item Sense of
      Coherence questionnaire). The results were controlled for patient
      characteristics. RESULTS: Participation was statistically predicted by different
      determinants depending on the operationalization used for participation.
      Additionally, the regression coefficients differed significantly. Body functions
      and activities were predictors in five out of six operationalizations of
      participation. Sense of coherence predicted participation in all of the
      operationalizations. The explained variance of the different models ranged from
      25% (RAND-36 role limitations-emotional) to 65% (Neuromuscular Disease Impact
      Profile). CONCLUSIONS: Different operationalizations of participation result in
      different prediction models. Lack of conceptual consensus makes participation an
      ambiguous concept in research, and this ambiguity makes evidence-based decisions
      directed at enhancing participation difficult. Participation needs to be
      operationalized in an unambiguous and standard way in order to improve the
      comparability of outcomes.

PMID- 24917588
TI  - Adhesive taping vs. daily manual muscle stretching and splinting after botulinum
      toxin type A injection for wrist and fingers spastic overactivity in stroke
      patients: a randomized controlled trial.
AB  - OBJECTIVE: To compare the effectiveness of two procedures increasing the
      botulinum toxin type A effect for wrist and finger flexor spasticity after
      stroke. DESIGN: A single-blind randomized trial. SUBJECTS: Seventy patients with
      upper limb post-stroke spasticity. METHODS: Adults with wrist and finger flexor
      muscles spasticity after stroke were submitted to botulinum toxin type A therapy.
      After the treatment, the subjects injected were randomly divided into two groups
      and submitted to adhesive taping (Group A) or daily muscle manual stretching,
      passive articular mobilization of wrist and fingers, and palmar splint (Group B)
      for 10 days. We measured spasticity with Modified Ashworth Scale, related
      disability with Disability Assessment Scale, and fingers position at rest. The
      measurements were done at baseline, after two weeks, and after one month from the
      treatment session. RESULTS: After two weeks, subjects in Group A reported a
      significantly greater decrease in spasticity scores (Modified Ashworth Scale
      fingers: mean (standard deviation) 1.3+/-0.6 vs. 2.1+/-0.6; Modified Ashworth
      Scale wrist: 1.7 +/-0.6 vs. 2.3 +/-0.8), and after one month in spasticity and
      disability scores (Modified Ashworth Scale fingers: mean (standard deviation) 1.9
      +/-0.7 vs. 2.5 +/-0.6; Modified Ashworth Scale wrist: 2.0 +/-0.7 vs. 2.6 +/-0.6;
      Disability Assessment Scale: 1.6 +/-0.7 vs. 2.1 +/-0.7) compared with Group B
      subjects. Subjects in Group A reported also a significantly improved fingers
      position at rest compared with Group B subjects after two weeks (2.8 +/-0.9 vs.
      2.1 +/-0.7) and one month (2.3 +/-0.7 vs. 1.5 +/-0.6). CONCLUSIONS: Adhesive
      taping of wrist and finger flexor muscles appeared to enhance the effect of
      botulinum toxin type A therapy more than daily manual muscle stretching combined
      with passive articular mobilization and palmar splint.

PMID- 24917589
TI  - Systematic review of the psychometric properties of balance measures for
      cerebellar ataxia.
AB  - OBJECTIVE: To review systematically the psychometric properties of balance
      measures for use in people with cerebellar ataxia. DATA SOURCES: Medline, AMED,
      CINAHL, Web of Science and EMBASE were searched between 1946 and April 2014.
      REVIEW METHODS: Two reviewers independently searched data sources. Cerebellar
      specific and generic measures of balance were considered. Included studies tested
      psychometric properties of balance measures in people with cerebellar ataxia of
      any cause. Quality of reported studies was rated using the Consensus Based
      Standards for the selection of health status Measurement INstruments (COSMIN)
      checklist. RESULTS: Twenty-one articles across which 16 measures had been tested
      were included for review. Using the COSMIN, quality of methodology in studies
      investigating psychometric properties of generic balance measures (n=10) was
      rated predominantly as 'poor'. Furthermore, responsiveness has not been tested
      for any generic measures in this population. The quality of studies investigating
      psychometric properties of balance sub-components of the cerebellar-specific
      measures (n=6) ranged from 'poor' to 'excellent'; however, Minimally Clinically
      Important Difference has not been determined for these cerebellar-specific
      measures. CONCLUSION: The Posture and Gait (PG) sub-component of the
      International Cooperative Ataxia Rating Scale (ICARS) demonstrates the most
      robust psychometric properties with acceptable clinical utility.

PMID- 24917590
TI  - What are the factors that influence physical activity participation in adults
      with knee and hip osteoarthritis? A systematic review of physical activity
      correlates.
AB  - OBJECTIVE: To determine the factors associated with physical activity
      participation in adults with hip or knee osteoarthritis. METHODS: A systematic
      review was conducted including searches of AMED, PsycINFO, CINAHL, MEDLINE,
      EMBASE, PubMed and the Cochrane Library from inception until October 2013.
      Studies presenting quantitative correlates of physical activity in adults with
      hip and/or knee osteoarthritis were included. Two independent authors conducted
      the searches, extracted data and completed methodological quality assessment.
      Correlates were analysed using the summary code approach within the socio
      ecological model. RESULTS: A total of 170 correlates were identified from 29
      publications analysing 8076 individual people with hip or knee osteoarthritis.
      Methodological quality was generally good. For knee osteoarthritis, factors
      consistently negatively associated with physical activity (reported more than
      four studies) were increasing age (number of participants in studies supporting
      association = 4558), non-white ethnicity (n = 3232), increased osteoarthritis
      symptoms (n = 2374) and female gender (n = 4816). Greater lower limb function (n
      = 1671) and faster gait speed were (n = 4098) positively associated with physical
      activity. Social (e.g. support from spouse (n = 141)) and environment (outdoor
      temperature (n = 38)) factors were identified as possible factors that influence
      physical activity. For hip osteoarthritis, higher body mass index (n = 99),
      increased comorbidities (n = 1021), lower mental health (n = 189) and
      unemployment (n = 65) were negatively associated with physical activity; while
      better social functioning (n = 1055) and health-related quality of life were
      positively associated with physical activity (n = 34). CONCLUSION: Demographic,
      physical, social, psychological and environmental factors are all important
      correlates for physical activity for people with knee or hip osteoarthritis.
      Clinicians should consider these in clinical practice.

PMID- 24917592
TI  - T cell receptor-dependent activation of mTOR signaling in T cells is mediated by
      Carma1 and MALT1, but not Bcl10.
AB  - Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse
      cellular processes, including protein translation, cellular proliferation,
      metabolism, and autophagy. Most models place Akt upstream of the mTOR complex,
      mTORC1; however, in T cells, Akt may not be necessary for mTORC1 activation. We
      found that the adaptor protein Carma1 [caspase recruitment domain (CARD)
      containing membrane-associated protein 1] and at least one of its associated
      proteins, the paracaspase MALT1 (mucosa-associated lymphoid tissue lymphoma
      translocation protein 1), were required for optimal activation of mTOR in T cells
      in response to stimulation of the T cell receptor (TCR) and the co-receptor CD28.
      However, Bcl10, which binds to Carma1 and MALT1 to form a complex that mediates
      signals from the TCR to the transcription factor NF-kappaB (nuclear factor
      kappaB), was not required. The catalytic activity of MALT1 was required for the
      proliferation of stimulated CD4+ T cells, but not for early TCR-dependent
      activation events. Consistent with an effect on mTOR, MALT1 activity was required
      for the increased metabolic flux in activated CD4+ T cells. Together, our data
      suggest that Carma1 and MALT1 play previously unappreciated roles in the
      activation of mTOR signaling in T cells after engagement of the TCR.

PMID- 24917591
TI  - Interplay between the oxidoreductase PDIA6 and microRNA-322 controls the response
      to disrupted endoplasmic reticulum calcium homeostasis.
AB  - The disruption of the energy or nutrient balance triggers endoplasmic reticulum
      (ER) stress, a process that mobilizes various strategies, collectively called the
      unfolded protein response (UPR), which reestablish homeostasis of the ER and
      cell. Activation of the UPR stress sensor IRE1alpha (inositol-requiring enzyme
      1alpha) stimulates its endoribonuclease activity, leading to the generation of
      the mRNA encoding the transcription factor XBP1 (X-box binding protein 1), which
      regulates the transcription of genes encoding factors involved in controlling the
      quality and folding of proteins. We found that the activity of IRE1alpha was
      regulated by the ER oxidoreductase PDIA6 (protein disulfide isomerase A6) and the
      microRNA miR-322 in response to disruption of ER Ca2+ homeostasis. PDIA6
      interacted with IRE1alpha and enhanced IRE1alpha activity as monitored by
      phosphorylation of IRE1alpha and XBP1 mRNA splicing, but PDIA6 did not
      substantially affect the activity of other pathways that mediate responses to ER
      stress. ER Ca2+ depletion and activation of store-operated Ca2+ entry reduced the
      abundance of the microRNA miR-322, which increased PDIA6 mRNA stability and,
      consequently, IRE1alpha activity during the ER stress response. In vivo
      experiments with mice and worms showed that the induction of ER stress correlated
      with decreased miR-322 abundance, increased PDIA6 mRNA abundance, or both.
      Together, these findings demonstrated that ER Ca2+, PDIA6, IRE1alpha, and miR-322
      function in a dynamic feedback loop modulating the UPR under conditions of
      disrupted ER Ca2+ homeostasis.

PMID- 24917593
TI  - Memo is a copper-dependent redox protein with an essential role in migration and
      metastasis.
AB  - Memo is an evolutionarily conserved protein with a critical role in cell
      motility. We found that Memo was required for migration and invasion of breast
      cancer cells in vitro and spontaneous lung metastasis from breast cancer cell
      xenografts in vivo. Biochemical assays revealed that Memo is a copper-dependent
      redox enzyme that promoted a more oxidized intracellular milieu and stimulated
      the production of reactive oxygen species (ROS) in cellular structures involved
      in migration. Memo was also required for the sustained production of the ROS O2-
      by NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 1
      (NOX1) in breast cancer cells. Memo abundance was increased in >40% of the
      primary breast tumors tested, was correlated with clinical parameters of
      aggressive disease, and was an independent prognostic factor of early distant
      metastasis.

PMID- 24917594
TI  - Isotype switching increases efficacy of antibody protection against
      staphylococcal enterotoxin B-induced lethal shock and Staphylococcus aureus
      sepsis in mice.
AB  - Staphylococcal enterotoxin B (SEB) is a potent toxin that is produced by
      Staphylococcus aureus strains and is classified as a category B select agent. We
      have previously shown that monoclonal antibody (MAb) 20B1, a murine anti-SEB
      IgG1, successfully treats SEB-induced lethal shock (SEBILS) and bacteremia that
      is caused by SEB-producing S. aureus. In this study, we have generated two
      isotype switch variants of the original IgG1 MAb 20B1, an IgG2a and IgG2b, both
      bearing the same variable region sequence, and compared their neutralizing and
      protective activity in in vitro and in vivo assays, respectively. All 3 isotypes
      demonstrated comparable affinity to SEB and comparable 50% inhibitory
      concentrations (IC50s) in T cell proliferation assays. In vivo, however, the
      IgG2a isotype variant of 20B1 exhibited significantly greater protection than
      IgG1 or IgG2b in murine SEB intoxication and S. aureus sepsis models. Protection
      was associated with downmodulation of inflammatory host response. Our data
      demonstrate that changing the isotype of already protective MAbs, without
      affecting their antigen specificity or sensitivity, can result in an enhancement
      of their protective ability. Isotype selection, therefore, should be carefully
      considered in the development of toxin-neutralizing MAbs and the design of
      antibody therapeutics. IMPORTANCE: The purpose of this study was to enhance the
      protective efficacy of an existing, protective monoclonal antibody against
      staphylococcal enterotoxin B. Using two in vivo mouse models, our study
      demonstrates that the protective efficacy of a monoclonal antibody may be
      improved by inducing an isotype switch at the Fc region of an antibody, without
      altering the antigen specificity or sensitivity of the antibody. The development
      of therapeutic MAbs with higher efficacy may allow for the achievement of equal
      therapeutic benefit with a lower dosage. In turn, the use of lower doses may
      reduce the cost of these therapies, while reducing the potential for adverse side
      effects.

PMID- 24917595
TI  - Saccharomyces boulardii administration changes gut microbiota and reduces hepatic
      steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic
      db/db mice.
AB  - Growing evidence shows that gut microbes are key factors involved in the
      regulation of energy homeostasis, metabolic inflammation, lipid metabolism, and
      glucose metabolism. Therefore, gut microbiota modulations caused by selectively
      fermented oligosaccharides or probiotic bacteria constitute an interesting target
      in the physiopathology of obesity. However, to date, no probiotic yeast has been
      investigated in this context. Therefore, our study aimed to evaluate the impact
      of the most-studied probiotic yeast (i.e., Saccharomyces boulardii Biocodex) on
      obesity and associated metabolic features, such as fat mass development, hepatic
      steatosis, and low-grade inflammation, in obese mice. S. boulardii was
      administered daily by oral gavage to leptin-resistant obese and type 2 diabetic
      mice (db/db) for 4 weeks. We found that S. boulardii-treated mice exhibited
      reduced body weight, fat mass, hepatic steatosis, and inflammatory tone.
      Interestingly, these effects of S. boulardii on host metabolism were associated
      with local effects in the intestine. S. boulardii increased cecum weight and
      cecum tissue weight but also induced dramatic changes in the gut microbial
      composition at the phylum, family, and genus levels. These gut microbiota changes
      in response to S. boulardii may also be correlated with the host metabolism
      response. In conclusion, this study demonstrates for the first time that S.
      boulardii may act as a beneficial probiotic treatment in the context of obesity
      and type 2 diabetes. IMPORTANCE: To date, no probiotic yeast have been
      investigated in the context of obesity and type 2 diabetes. Here we found that
      type 2 diabetic and obese mice (db/db) treated with Saccharomyces boulardii
      exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory
      tone. These effects on host metabolism were associated with local effects in the
      intestine. Importantly, by using pyrosequencing, we found that S. boulardii
      treatment induces changes of the gut microbiota composition at the phylum,
      family, and genus levels. Moreover, we found that gut microbiota changes in
      response to S. boulardii were correlated with several host metabolism responses.

PMID- 24917596
TI  - Antigenic variation of clade 2.1 H5N1 virus is determined by a few amino acid
      substitutions immediately adjacent to the receptor binding site.
AB  - Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are
      genetically highly variable and have diversified into multiple phylogenetic
      clades over the past decade. Antigenic drift is a well-studied phenomenon for
      seasonal human influenza viruses, but much less is known about the antigenic
      evolution of HPAI H5N1 viruses that circulate in poultry. In this study, we
      focused on HPAI H5N1 viruses that are enzootic to Indonesia. We selected
      representative viruses from genetically distinct lineages that are currently
      circulating and determined their antigenic properties by hemagglutination
      inhibition assays. At least six antigenic variants have circulated between 2003,
      when H5N1 clade 2.1 viruses were first detected in Indonesia, and 2011. During
      this period, multiple antigenic variants cocirculated in the same geographic
      regions. Mutant viruses were constructed by site-directed mutagenesis to
      represent each of the circulating antigenic variants, revealing that antigenic
      differences between clade 2.1 viruses were due to only one or very few amino acid
      substitutions immediately adjacent to the receptor binding site. Antigenic
      variants of H5N1 virus evaded recognition by both ferret and chicken antibodies.
      The molecular basis for antigenic change in clade 2.1 viruses closely resembled
      that of seasonal human influenza viruses, indicating that the hemagglutinin of
      influenza viruses from different hosts and subtypes may be similarly restricted
      to evade antibody recognition. IMPORTANCE: Highly pathogenic avian influenza
      (HPAI) H5N1 viruses are responsible for severe outbreaks in both commercial and
      backyard poultry, causing considerable economic losses and regular zoonotic
      transmissions to humans. Vaccination is used increasingly to reduce the burden of
      HPAI H5N1 virus in poultry. Influenza viruses can escape from recognition by
      antibodies induced upon vaccination or infection through genetic changes in the
      hemagglutinin protein. The evolutionary patterns and molecular basis of antigenic
      change in HPAI H5N1 viruses are poorly understood, hampering formulation of
      optimal vaccination strategies. We have shown here that HPAI H5N1 viruses in
      Indonesia diversified into multiple antigenic variants, that antigenic
      differences were due to one or a very few substitutions near the receptor binding
      site, and that the molecular basis for antigenic change was remarkably similar to
      that for seasonal human influenza viruses. These findings have consequences for
      future vaccination and surveillance considerations and contribute to the
      understanding of the antigenic evolution of influenza viruses.

PMID- 24917597
TI  - The ADP-ribosyltransferase domain of the effector protein ExoS inhibits
      phagocytosis of Pseudomonas aeruginosa during pneumonia.
AB  - Pseudomonas aeruginosa is a Gram-negative pathogen commonly associated with
      nosocomial infections such as hospital-acquired pneumonia. It uses a type III
      secretion system to deliver effector proteins directly into the cytosol of host
      cells. Type III secretion in P. aeruginosa has been linked to severe disease and
      worse clinical outcomes in animal and human studies. The majority of P.
      aeruginosa strains secrete ExoS, a bifunctional toxin with GTPase-activating
      protein and ADP-ribosyltransferase activities. Numerous in vitro studies have
      investigated the targets and cellular effects of ExoS, linking both its enzymatic
      activities with inhibition of bacterial internalization. However, little is known
      about how this toxin facilitates the progression of infection in vivo. In this
      study, we used a mouse model to investigate the role of ExoS in inhibiting
      phagocytosis during pneumonia. We first confirmed previous findings that the ADP
      ribosyltransferase activity of ExoS, but not the GTPase-activating protein
      activity, was responsible for bacterial persistence and decreased host survival
      in this model. We then used two distinct assays to demonstrate that ExoS
      inhibited phagocytosis during pneumonia. In contrast to the findings of several
      in vitro studies, this in vivo inhibition was also dependent on the ADP
      ribosyltransferase activity, but not the GTPase-activating protein activity, of
      ExoS. These results demonstrate for the first time the antiphagocytic function of
      ExoS in the context of an actual infection and indicate that blocking the ADP
      ribosyltransferase activity of ExoS may have potential therapeutic benefit.
      IMPORTANCE: Pseudomonas aeruginosa is a major cause of hospital-acquired
      infections. To cause severe disease, this bacterium uses a type III secretion
      system that delivers four effector proteins, ExoS, ExoT, ExoU, and ExoY, into
      host cells. The majority of P. aeruginosa strains secrete ExoS, a bifunctional
      toxin with GTPase-activating protein and ADP-ribosyltransferase activities. In
      cell culture models, both enzymatic activities have been associated with
      decreased bacterial internalization. However, our study is the first to examine a
      role for ExoS in blocking phagocytosis in an animal model. We report that ExoS
      does inhibit phagocytosis during pneumonia. The ADP-ribosyltransferase activity,
      but not the GTPase-activating protein activity, of ExoS is necessary for this
      effect. Our findings highlight the ability of P. aeruginosa to manipulate the
      inflammatory response during pneumonia to facilitate bacterial survival.

PMID- 24917598
TI  - A histone deacetylase complex mediates biofilm dispersal and drug resistance in
      Candida albicans.
AB  - Biofilms are resilient, surface-associated communities of cells with specialized
      properties (e.g., resistance to drugs and mechanical forces) that are distinct
      from those of suspension (planktonic) cultures. Biofilm formation by the
      opportunistic human fungal pathogen Candida albicans is medically relevant
      because C. albicans infections are highly correlated with implanted medical
      devices, which provide efficient substrates for biofilm formation; moreover,
      biofilms are inherently resistant to antifungal drugs. Biofilms are also
      important for C. albicans to colonize diverse niches of the human host. Here, we
      describe four core members of a conserved histone deacetylase complex in C.
      albicans (Set3, Hos2, Snt1, and Sif2) and explore the effects of their mutation
      on biofilm formation. We find that these histone deacetylase complex members are
      needed for proper biofilm formation, including dispersal of cells from biofilms
      and multifactorial drug resistance. Our results underscore the importance of the
      physical properties of biofilms in contributing to drug resistance and dispersal
      and lay a foundation for new strategies to target biofilm dispersal as a
      potential antifungal intervention. IMPORTANCE: Through the formation of biofilms-
      surface-associated communities of cells--microorganisms can establish infections,
      become drug resistant, and evade the host immune system. Here we investigate how
      four core members of a conserved histone deacetylase complex mediate biofilm
      formation by Candida albicans, the major fungal pathogen of humans. We show that
      this histone deacetylase complex is required for biofilm dispersal, a process
      through which cells leave the biofilm to establish new infections. We also show
      that the deacetylase complex mediates biofilm drug resistance. This work provides
      new insight into how the physical properties of biofilms affect dispersal and
      drug resistance and suggests new potential antifungal strategies that could be
      effective against biofilms.

PMID- 24917599
TI  - Bacteria present in carotid arterial plaques are found as biofilm deposits which
      may contribute to enhanced risk of plaque rupture.
AB  - Atherosclerosis, a disease condition resulting from the buildup of fatty plaque
      deposits within arterial walls, is the major underlying cause of ischemia
      (restriction of the blood), leading to obstruction of peripheral arteries,
      congestive heart failure, heart attack, and stroke in humans. Emerging research
      indicates that factors including inflammation and infection may play a key role
      in the progression of atherosclerosis. In the current work, atherosclerotic
      carotid artery explants from 15 patients were all shown to test positive for the
      presence of eubacterial 16S rRNA genes. Density gradient gel electrophoresis of 5
      of these samples revealed that each contained 10 or more distinct 16S rRNA gene
      sequences. Direct microscopic observation of transverse sections from 5 diseased
      carotid arteries analyzed with a eubacterium-specific peptide nucleic acid probe
      revealed these to have formed biofilm deposits, with from 1 to 6 deposits per
      thin section of plaque analyzed. A majority, 93%, of deposits was located
      proximal to the internal elastic lamina and associated with fibrous tissue. In 6
      of the 15 plaques analyzed, 16S rRNA genes from Pseudomonas spp. were detected.
      Pseudomonas aeruginosa biofilms have been shown in our lab to undergo a
      dispersion response when challenged with free iron in vitro. Iron is known to be
      released into the blood by transferrin following interaction with catecholamine
      hormones, such as norepinephrine. Experiments performed in vitro showed that
      addition of physiologically relevant levels of norepinephrine induced dispersion
      of P. aeruginosa biofilms when grown under low iron conditions in the presence
      but not in the absence of physiological levels of transferrin. IMPORTANCE: The
      association of bacteria with atherosclerosis has been only superficially studied,
      with little attention focused on the potential of bacteria to form biofilms
      within arterial plaques. In the current work, we show that bacteria form biofilm
      deposits within carotid arterial plaques, and we demonstrate that one species we
      have identified in plaques can be stimulated in vitro to undergo a biofilm
      dispersion response when challenged with physiologically relevant levels of
      norepinephrine in the presence of transferrin. Biofilm dispersion is
      characterized by the release of bacterial enzymes into the surroundings of
      biofilm microcolonies, allowing bacteria to escape the biofilm matrix. We believe
      these enzymes may have the potential to damage surrounding tissues and facilitate
      plaque rupture if norepinephrine is able to stimulate biofilm dispersion in vivo.
      This research, therefore, suggests a potential mechanistic link between hormonal
      state and the potential for heart attack and stroke.

PMID- 24917600
TI  - Acellular pertussis vaccines and pertussis resurgence: revise or replace?
AB  - The resurgence of pertussis (whooping cough) in countries with high vaccination
      coverage is alarming and invites reconsideration of the use of current acellular
      pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole
      cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited
      antigenic composition and early waning of antibody levels could be anticipated by
      the results of in-trial or postlicensure human investigations of B- and T-cell
      responses in aP versus wP vaccine recipients or unvaccinated, infected children.
      Recent data in experimental models, including primates, suggest that generation
      of vaccines capable of a potent, though regulated, stimulation of innate immunity
      driving effective, persistent adaptive immune responses against Bordetella
      pertussis infection should be privileged. Adjuvants that skew Th1/Th17 responses
      or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless,
      the high merits of the current aP vaccines in persuading people to resume
      vaccination against pertussis should not be forgotten. 

PMID- 24917601
TI  - New clues to understanding HIV nonprogressors: low cholesterol blocks HIV trans
      infection.
AB  - A small percentage of HIV-infected subjects (2 to 15%) are able to control
      disease progression for many years without antiretroviral therapy. Years of
      intense studies of virologic and immunologic mechanisms of disease control in
      such individuals yielded a number of possible host genes that could be
      responsible for the preservation of immune functions, from immune surveillance
      genes, chemokines, or their receptors to anti-HIV restriction factors. A recent
      mBio paper by Rappocciolo et al. (G. Rappocciolo, M. Jais, P. Piazza, T. A.
      Reinhart, S. J. Berendam, L. Garcia-Exposito, P. Gupta, and C. R. Rinaldo, mBio
      5:e01031-13, 2014) describes another potential factor controlling disease
      progression: cholesterol levels in antigen-presenting cells. In this commentary,
      we provide a brief background of the role of cholesterol in HIV infection,
      discuss the results of the study by Rappocciolo et al., and present the
      implications of their findings. 

PMID- 24917602
TI  - For patients with chronic asthma not controlled with inhaled corticosteroids
      alone, long-acting beta-agonists are associated with fewer exacerbations than
      leukotriene receptor agonists.

PMID- 24917603
TI  - Network meta-analysis demonstrates the safety of pharmacotherapy for smoking
      cessation in cardiovascular patients.

PMID- 24917604
TI  - A low Wells score and a negative D-dimer was not safe in patients with cancer for
      ruling out DVT.

PMID- 24917605
TI  - Trial suggests yoga and exercise lead to modest improvements in menopause-related
      quality of life: longer term studies are needed.

PMID- 24917606
TI  - The accuracy of V/Q SPECT in the diagnosis of pulmonary embolism: a meta
      analysis.
AB  - BACKGROUND: Ventilation perfusion single photon emission computed tomography (V/Q
      SPECT) and CT pulmonary angiography have all been used in the diagnosis of acute
      PE. Previous studies have shown higher sensitivity and specificity and a marked
      decrease in the non-diagnostic rate of V/Q SPECT than planar scan. PURPOSE: To
      systematically review and perform a meta-analysis of published data on the
      performance of V/Q SPECT in the diagnosis of acute PE. MATERIAL AND METHODS: A
      comprehensive computer search was conducted on literature published through 31
      December 2013 in an effort to find relevant articles on the diagnostic
      performance of V/Q SPECT in the diagnosis of PE patients. Pooled sensitivity,
      specificity, negative likelihood ratio (LR), and positive LR, the area under the
      receiver-operating characteristic (ROC) curve of V/Q SPECT in the diagnosis of PE
      patients were calculated. RESULTS: Nine studies, comprising a total sample size
      of 3454 patients, were included in our meta-analysis. The pooled sensitivity,
      specificity of V/Q SPECT in the diagnosis of acute PE patients, calculated on a
      per-patient-based analysis, was 96% (95% confidence interval [CI], 95-97%), 97%
      (95% CI, 96-98%). The pooled negative LR, positive LR of V/Q SPECT in acute PE
      patients was 0.06 (range, 0.02-0.19) and 16.64 (range, 9.78-31.54). The area
      under the ROC curve of V/Q SPECT in the diagnosis of acute PE patients was 0.99
      on a per-patient-based analysis. CONCLUSION: V/Q SPECT is an accurate method in
      acute PE patients with high sensitivity and high specificity in the diagnosis of
      PE.

PMID- 24917607
TI  - Chest X-ray and CT findings of early H7N9 avian influenza cases.
AB  - BACKGROUND: The H7N9 strain of bird flu is a new type of avian flu that was
      identified at the end of March 2013. The disease is concerning because most
      patients have become severely ill. PURPOSE: To study the X-ray and computed
      tomography (CT) findings of early H7N9 avian influenza cases. MATERIAL AND
      METHODS: Chest radiography and CT were performed in six patients with H7N9 avian
      influenza within 1-20 days after onset. The CT examinations included conventional
      spiral CT and high-resolution CT. The findings on the radiography and CT images
      were analyzed. RESULTS: Abnormal X-ray and CT findings were present in all of the
      patients. All of the cases had acute onset. In the early stage, the right lung
      was more commonly affected (particularly in the right upper and middle lobes).
      The lesions rapidly expanded to the entire lungs and were characterized primarily
      by ground-glass opacities (GGOs) combined with consolidation. Diffuse GGO was
      observed in all six cases (1 was symmetric, and 5 were non-symmetric). Local
      consolidation was found in four cases, and lobar consolidation was found in two
      cases. Normal lung tissue was observed between the lesions. Pleural thickening
      was common and was combined with pleural/pericardial effusion or mediastinal
      lymph node enlargement. Reticular changes, centrilobular nodules, and the tree-in
      bud sign were observed in some cases, but reticular changes, bronchial wall
      thickening, and hyperinflation were not found. CONCLUSION: Radiological changes
      associated with both acute pneumonia and acute interstitial inflammation were
      observed in early H7N9 avian influenza cases. Serial chest X-rays were useful for
      the diagnosis and severity assessment of the disease. CT may provide a more
      accurate assessment of the lung pathology.

PMID- 24917608
TI  - Quantitative assessment of pulmonary perfusion using dynamic contrast-enhanced CT
      in patients with chronic obstructive pulmonary disease: correlations with
      pulmonary function test and CT volumetric parameters.
AB  - BACKGROUND: Pulmonary function test (PFT) is commonly used to help diagnose
      chronic obstructive pulmonary disease (COPD) and other lung diseases. However, it
      cannot be used to evaluate regional function and morphological abnormalities.
      PURPOSE: To quantitatively evaluate pulmonary perfusion imaging using dynamic
      contrast-enhanced (DCE) computed tomography (CT) and observe its correlations
      with PFT and CT volumetric parameters in COPD patients. MATERIAL AND METHODS: PFT
      and CT pulmonary perfusion examination were performed in 63 COPD patients.
      Perfusion defects were quantitated by calculating the CT value ratio (RHU)
      between perfusion defects (HUdefect) and normal lung (HUnormal). Volumetric CT
      data were used to calculate emphysema index (EI), total lung volume (TLV), and
      total emphysema volume (TEV). Emphysematous parenchyma was defined as the
      threshold of lung area lower than -950 HU. Correlations between RHU and TLV, TEV,
      EI, and PFT were assessed using Spearman correlation analysis. RESULTS: The
      positive rate of perfusion defects on CT perfusion images was higher than that of
      emphysema on CT mask images (chi(2) = 17.027, P < 0.001). The Spearman
      correlation test showed that RHU was positively correlated with FEV1 (R = 0.59, P
      < 0.001), FEV1% Predicted (R = 0.61, P < 0.001), FVC (R = 0.47, P = 0.002), and
      FEV1/FVC (R = 0.65, P < 0.001), and negatively correlated with EI (R = -0.67, P <
      0.001). CONCLUSION: CT perfusion imaging is more sensitive in detecting emphysema
      that is inconspicuous on CT images. RHU is correlated with PFT and CT volumetric
      parameters, suggesting that it is more sensitive in detecting early COPD changes
      and may prove to be a potential predictor of focal lung function.

PMID- 24917609
TI  - Diagnostic value of dual time-point 18 F-FDG PET/CT versus single time-point
      imaging for detection of mediastinal nodal metastasis in non-small cell lung
      cancer patients: a meta-analysis.
AB  - BACKGROUND: Lymph node staging in non-small cell lung cancer (NSCLC) is
      challenging and important for determining treatment policy. Conflicting results
      have been presented to date. PURPOSE: To evaluate the diagnostic performance of
      dual time-point (DTP) 18 F-FDG PET/CT compared with single time-point (STP)
      imaging for detecting mediastinal nodal metastases in patients with NSCLC.
      MATERIAL AND METHODS: The PubMed, EMBASE, EBSCO, and Web of Knowledge databases
      were searched for relevant articles. The pooled sensitivity, specificity,
      diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative
      likelihood ratio (NLR) were calculated using Meta-Disc software. Summary receiver
      operating characteristic (SROC) curves were also constructed. The potential for
      between-study heterogeneity was explored using subgroup analyses. RESULTS: A
      total of eight studies involving 654 patients fulfilled the inclusion criteria.
      On a per-patient analysis, the pooled sensitivity and specificity with a 95%
      confidence interval (CI) for DTP PET/CT were 0.85 (0.78-0.91), 0.75 (0.68-0.82),
      and for STP imaging, they were 0.79 (0.70-0.85), 0.73 (0.65-0.79), respectively.
      On a per-lesion basis, the corresponding values for DTP imaging were 0.84 (0.81
      0.86), 0.89 (0.87-0.91), and for STP imaging, they were 0.84 (0.80-0.86), 0.83
      (0.81-0.85), respectively. CONCLUSION: DTP PET/CT performed better than STP
      imaging in evaluating the lymph node status of NSCLC patients and had the
      potential to be broadly applied in clinical practice. However, due to the small
      sample size and large heterogeneity, current evidence does not justify the
      implementation of DTP imaging in routine PET protocols for mediastinal lymph node
      staging of NSCLC.

PMID- 24917610
TI  - The global phosphoproteome of Chlamydomonas reinhardtii reveals complex
      organellar phosphorylation in the flagella and thylakoid membrane.
AB  - Chlamydomonas reinhardtii is the most intensively-studied and well-developed
      model for investigation of a wide-range of microalgal processes ranging from
      basic development through understanding triacylglycerol production. Although
      proteomic technologies permit interrogation of these processes at the protein
      level and efforts to date indicate phosphorylation-based regulation of proteins
      in C. reinhardtii is essential for its underlying biology, characterization of
      the C. reinhardtii phosphoproteome has been limited. Herein, we report the
      richest exploration of the C. reinhardtii proteome to date. Complementary
      enrichment strategies were used to detect 4588 phosphoproteins distributed among
      every cellular component in C. reinhardtii. Additionally, we report 18,160 unique
      phosphopeptides at <1% false discovery rate, which comprise 15,862 unique
      phosphosites - 98% of which are novel. Given that an estimated 30% of proteins in
      a eukaryotic cell are subject to phosphorylation, we report the majority of the
      phosphoproteome (23%) of C. reinhardtii. Proteins in key biological pathways were
      phosphorylated, including photosynthesis, pigment production, carbon
      assimilation, glycolysis, and protein and carbohydrate metabolism, and it is
      noteworthy that hyperphosphorylation was observed in flagellar proteins. This
      rich data set is available via ProteomeXchange (ID: PXD000783) and will
      significantly enhance understanding of a range of regulatory mechanisms
      controlling a variety of cellular process and will serve as a critical resource
      for the microalgal community. 

PMID- 24917611
TI  - Diversity within the O-linked protein glycosylation systems of acinetobacter
      species.
AB  - The opportunistic human pathogen Acinetobacter baumannii is a concern to health
      care systems worldwide because of its persistence in clinical settings and the
      growing frequency of multiple drug resistant infections. To combat this threat,
      it is necessary to understand factors associated with disease and environmental
      persistence of A. baumannii. Recently, it was shown that a single biosynthetic
      pathway was responsible for the generation of capsule polysaccharide and O-linked
      protein glycosylation. Because of the requirement of these carbohydrates for
      virulence and the non-template driven nature of glycan biogenesis we investigated
      the composition, diversity, and properties of the Acinetobacter glycoproteome.
      Utilizing global and targeted mass spectrometry methods, we examined 15 strains
      and found extensive glycan diversity in the O-linked glycoproteome of
      Acinetobacter. Comparison of the 26 glycoproteins identified revealed that
      different A. baumannii strains target similar protein substrates, both in
      characteristics of the sites of O-glycosylation and protein identity.
      Surprisingly, glycan micro-heterogeneity was also observed within nearly all
      isolates examined demonstrating glycan heterogeneity is a widespread phenomena in
      Acinetobacter O-linked glycosylation. By comparing the 11 main glycoforms and
      over 20 alternative glycoforms characterized within the 15 strains, trends within
      the glycan utilized for O-linked glycosylation could be observed. These trends
      reveal Acinetobacter O-linked glycosylation favors short (three to five residue)
      glycans with limited branching containing negatively charged sugars such as
      GlcNAc3NAcA4OAc or legionaminic/pseudaminic acid derivatives. These observations
      suggest that although highly diverse, the capsule/O-linked glycan biosynthetic
      pathways generate glycans with similar characteristics across all A. baumannii. 

PMID- 24917612
TI  - Red, amber and green: the role of the lung in de-priming active systemic
      neutrophils.

PMID- 24917616
TI  - Parents who wish no further treatment for their child.
AB  - BACKGROUND: In the ethical and clinical literature, cases of parents who want
      treatment for their child to be withdrawn against the views of the medical team
      have not received much attention. Yet resolution of such conflicts demands much
      effort of both the medical team and parents. OBJECTIVE: To discuss who can best
      protect a child's interests, which often becomes a central issue, putting
      considerable pressure on mutual trust and partnership. METHODS: We describe the
      case of a 3-year-old boy with acquired brain damage due to autoimmune-mediated
      encephalitis whose parents wanted to stop treatment. By comparing this case with
      relevant literature, we systematically explored the pros and cons of sharing end
      of-life decisions with parents in cases where treatment is considered futile by
      parents and not (yet) by physicians. CONCLUSIONS: Sharing end-of-life decisions
      with parents is a more important duty for physicians than protecting parents from
      guilt or doubt. Moreover, a request from parents on behalf of their child to
      discontinue treatment is, and should be, hard to over-rule in cases with
      significant prognostic uncertainty and/or in cases with divergent opinions within
      the medical team.

PMID- 24917618
TI  - Identification of the 'Streptococcus anginosus group' by matrix-assisted laser
      desorption ionization--time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) provides rapid, accurate and cost-effective identification of a
      range of bacteria and is rapidly changing the face of routine diagnostic
      microbiology. However, certain groups of bacteria, for example streptococci (in
      particular viridans or non-haemolytic streptococci), are less reliably identified
      by this method. We studied the performance of MALDI-TOF MS for identification of
      the 'Streptococcus anginosus group' (SAG) to species level. In total, 116 stored
      bacteraemia isolates identified by conventional methods as belonging to the SAG
      were analysed by MALDI-TOF MS. Partial 16S rRNA gene sequencing, supplemented
      with sialidase activity testing, was performed on all isolates to provide 'gold
      standard' identification against which to compare MALDI-TOF MS performance.
      Overall, 100 % of isolates were correctly identified to the genus level and 93.1
      % to the species level by MALDI-TOF MS. However, only 77.6 % were correctly
      identified to the genus level and 59.5 % to the species level by a MALDI-TOF MS
      direct transfer method alone. Use of a rapid in situ extraction method
      significantly improved identification rates when compared with the direct
      transfer method (P<0.001). We recommend routine use of this method to reduce the
      number of time-consuming full extractions required for identification of this
      group of bacteria by MALDI-TOF MS in the routine diagnostic laboratory. Only 22 %
      (1/9) of Streptococcus intermedius isolates were reliably identified by MALDI-TOF
      MS to the species level, even after full extraction. MALDI-TOF MS reliably
      identifies S. anginosus and Streptococcus constellatus to the species level but
      does not reliably identify S. intermedius. 

PMID- 24917624
TI  - Shorter training is no solution for building the primary care physician
      workforce.

PMID- 24917617
TI  - Trends in cigarette pricing and purchasing patterns in a sample of US smokers:
      findings from the ITC US Surveys (2002-2011).
AB  - OBJECTIVE: This paper examines trends in cigarette prices and corresponding
      purchasing patterns over a 9-year period and explores characteristics associated
      with the quantity and location of cigarettes purchased by adult smokers in the
      USA. METHODS: The data for this paper come from a nationally representative
      longitudinal survey of 6669 adult smokers (18 years and older) who were recruited
      and surveyed between 2002 and 2011. Telephone interviews were conducted annually,
      and smokers were asked a series of questions about the location, quantity (ie,
      single vs multiple packs or cartons) and price paid for their most recent
      cigarette purchase. Generalised estimating equations were used to assess trends
      and model characteristics associated with cigarette purchasing behaviours.
      RESULTS: Between 2002 and 2011, the reported purchase of cigarette cartons and
      the use of coupons declined while multipack purchases increased. Compared with
      those purchasing by single packs, those who purchased by multipacks and cartons
      saved an average of $0.53 and $1.63, respectively. Purchases in grocery and
      discount stores declined, while purchases in tobacco only outlets increased
      slightly. Female, older, white smokers were more likely to purchase cigarettes by
      the carton or in multipacks and in locations commonly associated with tax
      avoidance (ie, duty free shops, Indian reservations). CONCLUSIONS: As cigarette
      prices have risen, smokers have begun purchasing via multipacks instead of
      cartons. As carton sales have declined, purchases from grocery and discount
      stores have also declined, while an increasing number of smokers report low tax
      sources as their usual purchase location for cigarettes.

PMID- 24917625
TI  - A new model for educating our nation's primary care physicians.

PMID- 24917626
TI  - Effect of inpatient electroencephalography on clinical decision making: EEG is
      more valuable than findings suggest.

PMID- 24917627
TI  - Effect of inpatient electroencephalography on clinical decision making: EEG is
      more valuable than findings suggest.

PMID- 24917628
TI  - Effect of inpatient electroencephalography on clinical decision making: EEG is
      more valuable than findings suggest. Response.

PMID- 24917631
TI  - Effect of osteopathic manipulative treatment on middle ear effusion following
      acute otitis media in young children: a pilot study.
AB  - CONTEXT: Childhood acute otitis media (AOM) is highly prevalent. Its usual
      sequela of middle ear effusion (MEE) can lead to conductive hearing loss, for
      which surgery is commonly used. OBJECTIVE: To evaluate the efficacy of an
      osteopathic manipulative treatment (OMT) protocol on MEE resolution following an
      episode of AOM. The authors hypothesized that OMT provided adjunctively to
      standard care for young children with AOM would reduce the duration of MEE
      following the onset of AOM. METHODS: We compared standard care only (SCO) and
      standard care plus OMT (SC+OMT) for the duration of MEE following AOM. Patients
      were aged 6 months to 2 years. The SC+OMT group received OMT during 3 weekly
      visits. Weekly tympanometric and acoustic reflectometer (AR) readings were
      obtained from all patients. RESULTS: There were 52 patients enrolled, with 43
      completing the study and 9 dropping out. No demographic differences were noted.
      Only ears from each patient with abnormal tympanograms at entry were included.
      There were 76 ears in the tympanogram analysis (38 from SCO; 38 from SC+OMT) and
      61 ears in the AR data analysis (31 from SCO; 30 from SC+OMT). Dependence of
      bilateral ear disease noted in AR readings was accounted for in statistical
      analysis. Tympanogram data demonstrated a statistically significant improvement
      in MEE at visit 3 in patients in the SC+OMT group (odds ratio, 2.98; 95%
      confidence interval, 1.16, 7.62; chi(2) test for independence, P=.02). The AR
      data analysis showed statistically significant improvement at visit 3 for the
      SC+OMT group (z=2.05; P=.02). There was no statistically significant change in
      MEE before or immediately after the OMT protocol. CONCLUSION: A standardized OMT
      protocol administered adjunctively with standard care for patients with AOM may
      result in faster resolution of MEE following AOM than standard treatment alone.
      (ClinicalTrials.gov number NCT00520039.).

PMID- 24917632
TI  - Osteopathic manipulative treatment for inpatients with pulmonary exacerbations of
      cystic fibrosis: effects on spirometry findings and patient assessments of
      breathing, anxiety, and pain.
AB  - CONTEXT: Osteopathic manipulative treatment (OMT) has been studied in patients
      with various respiratory diseases. However, to the authors' knowledge, no studies
      have assessed the efficacy of OMT in patients with cystic fibrosis (CF).
      OBJECTIVE: To evaluate pulmonary function and perceptions of breathing, anxiety,
      and pain of CF patients who receive OMT in addition to standard inpatient
      management of pulmonary exacerbation. METHODS: In a single-blind randomized
      controlled trial, we assessed adult patients with a history of CF who were
      admitted to the hospital because of pulmonary exacerbation. Participants were
      randomly assigned to receive a daily standardized protocol of OMT or sham
      therapy. Both groups also received standard treatment for CF. Spirometry and
      questionnaire data (self-assessment of breathing, pain, and anxiety level) were
      collected before the first OMT or sham therapy session and after the final
      session. RESULTS: A total of 33 patients were included in the study: 16 in the
      OMT group and 17 in the sham therapy group. Improvements in spirometric
      parameters were observed in both the OMT and the sham therapy groups, with no
      statistically significant differences found between the groups. More patients in
      the OMT group than in the sham therapy group had questionnaire response patterns
      that indicated their breathing had improved during the study period (15 of 16 vs
      8 of 16, respectively). No differences were found between groups for perceived
      improvement of pain and anxiety. CONCLUSION: In the current study, CF patients
      who received OMT did not demonstrate statistically significant differences in pre
      and posttreatment spirometry findings compared with CF patients who received
      sham therapy. Questionnaire findings suggest that OMT may affect CF patients'
      perception of overall quality of breathing. Additional studies are needed to
      assess the clinical use of OMT in patients with CF.

PMID- 24917633
TI  - Assessing palpation thresholds of osteopathic medical students using static
      models of the lumbar spine.
AB  - CONTEXT: Although spinal somatic dysfunction diagnosis is taught at all colleges
      of osteopathic medicine, few objective measures have been used to evaluate
      student accuracy. OBJECTIVE: To assess the palpatory skills of osteopathic
      medical students in evaluating positional asymmetry in the transverse plane using
      static block transverse process and lumbar spine models. METHODS: For this
      observational study, first-year osteopathic medical students completed 3
      palpatory assessments using uncovered and covered block transverse process and
      lumbar spine models to simulate a range of positional asymmetries of the
      transverse processes. With use of logistic regression, 80%, 90%, and 95%
      thresholds were defined as the magnitude of asymmetry for which the predicted
      probability of students correctly determining the direction of asymmetry exceeded
      a specified amount (.80, .90, or .95). RESULTS: A total of 346 students completed
      the assessments. For the uncovered block transverse process model (assessment 1),
      students correctly identified the direction of asymmetry with .89 probability at
      1 mm of asymmetry (80% threshold), .94 probability at 2 mm (90% threshold), and
      .95 probability at 3 mm (95% threshold). For the covered block transverse process
      model, students correctly identified the direction of asymmetry with .80
      probability at 1 mm (80% threshold), .92 probability at 2 mm (90% threshold), and
      .98 probability at 3 mm (95% threshold) by the third assessment. For the
      uncovered lumbar spine model (assessment 2), students correctly identified the
      direction of asymmetry with .93 probability at 2 mm (80% and 90% thresholds) and
      .95 probability at 3 mm (95% threshold). For the covered lumbar spine model
      (assessments 2 and 3), students correctly identified the direction of asymmetry
      with .87 probability at 4 mm (80% threshold); 90% and 95% thresholds were not
      reached with the range of asymmetries tested. CONCLUSION: Most first-year
      osteopathic medical students were able to discern the direction of positional
      asymmetry of transverse processes on static models. Depending on the model type,
      student performance improved (block transverse process models) or declined
      (lumbar spine models) over time. Future studies should evaluate whether accuracy
      of palpating lumbar spine models translates to accuracy of palpating human lumbar
      spines.

PMID- 24917634
TI  - Effectiveness of osteopathic manipulative therapy for managing symptoms of
      irritable bowel syndrome: a systematic review.
AB  - CONTEXT: Irritable bowel syndrome (IBS) is a common and often lifelong functional
      gastrointestinal disorder. There is a scarcity of effective management options
      for IBS. OBJECTIVE: To assess the effectiveness of osteopathic manipulative
      therapy (OMTh) for managing the symptoms of IBS. DATA SOURCES: Articles without
      language or publication-date restriction were searched in PubMed, Embase,
      Cochrane Library, PEDro, OSTMED.DR, and Osteopathic Research Web. Search terms
      included irritable bowel syndrome, IBS, functional colonic disease, colon
      irritable, osteopath*, osteopathic manipulation, osteopathic medicine, clinical
      trial, and randomized clinical trial. Experts in the field of visceral osteopathy
      were also contacted to identify additional studies. STUDY SELECTION: The authors
      evaluated randomized controlled trials (RCTs) of OMTh for IBS in adults in whom
      IBS was diagnosed using Rome (I-III) criteria. If OMTh was not the sole
      intervention in the intervention group and if the same additional interventions
      were not applied to the control group, the study was excluded. DATA EXTRACTION:
      Citation identification, study selection, and data extraction were independently
      undertaken by 2 reviewers with a data extraction form from the Cochrane
      Collaboration. A consensus method was used to resolve disagreements concerning
      the assessment of the methodologic quality of the RCTs that were reviewed.
      RESULTS: The search identified 10 studies that examined OMTh for patients with
      IBS; 5 studies (204 patients) met the inclusion criteria. All studies were
      assessed as having low risk of bias according to the Cochrane Collaboration
      criteria, although there was heterogeneity in the outcome measures and control
      interventions. Three studies used visual analog scales for abdominal pain,
      whereas others used the IBS severity score and the Functional Bowel Disorder
      Severity Index. A variety of secondary outcomes were used. All studies reported
      more pronounced short-term improvements with OMTh compared with sham therapy or
      standard care only. These differences remained statistically significant after
      variable lengths of follow-up in 3 studies. CONCLUSION: The present systematic
      review provides preliminary evidence that OMTh may be beneficial in the treatment
      of patients with IBS. However, caution is required in the interpretation of these
      findings because of the limited number of studies available and the small sample
      sizes.

PMID- 24917635
TI  - Predictive relationship of osteopathic manual medicine grades and COMLEX-USA
      Level 1 total scores and osteopathic principles and practice subscores.
AB  - CONTEXT: Osteopathic manual medicine (OMM) encompasses hands-on diagnosis and
      treatment as part of patient care. The area of osteopathic principles and
      practice (OPP) is considered a core competency for students and practitioners of
      this medical tradition. The Comprehensive Osteopathic Medical Licensing
      Examination-USA (COMLEX-USA) is a useful tool for assessing candidates'
      competency. OBJECTIVES: To examine the relationship of COMLEX-USA Level 1 total
      scores and OPP subscores with OMM course grades, and to determine if these grades
      are predictive of COMLEX-USA Level 1 OPP performance. METHODS: The authors
      collected data-COMLEX-USA Level 1 total and OPP subscores, OMM grades (written,
      practical, and total for first and second academic years), sex, and age-for a
      cohort of osteopathic medical students at a single institution, and these data
      were then analyzed by means of correlation analysis. RESULTS: Records were
      obtained from a second-year class of osteopathic medical students (N=217). The
      authors' analysis of total scores and OPP subscores on COMLEX-USA Level 1 yielded
      a statistically significant correlation with all variables. Although the
      correlations were moderate, second-year written examination grades showed the
      strongest association with the COMLEX-USA Level 1 OPP subscores (r=0.530) and
      total scores (r=0.566). CONCLUSION: Performance in the second-year OMM written
      examination could identify students potentially at risk for poor performance on
      COMLEX-USA Level 1.

PMID- 24917636
TI  - From "Doctor of Osteopathy" to "Doctor of Osteopathic Medicine": a title change
      in the push for equality.
AB  - Nationally, the California merger created great solidarity among osteopathic
      members of state and national osteopathic associations. They rebuffed further
      efforts at amalgamation and championed the continuation of the DO degree. Even
      after the American Medical Association (AMA) opened its doors to DOs to join
      local and state medical associations as well as the AMA itself and gave its
      blessing to them entering allopathic residency programs and becoming MD board
      certified, the DOs stood fast for their independence. Yet some across the country
      wanted to become known as MDs. A few osteopathic physicians even went to federal
      court to claim-unsuccessfully-that state medical boards' refusal to license them
      or allow them to identify themselves as MDs violated their constitutional rights
      under the 1st and 14th Amendments. In the mid-1990s, the American Osteopathic
      Association (AOA) gave individual osteopathic medical colleges the option of
      indicating on their diplomas that the DO degree signified "Doctor of Osteopathic
      Medicine" rather than "Doctor of Osteopathy," a change that paralleled previous
      AOA policy changes regarding appropriate professional language. Nevertheless,
      some DOs and particularly a sizable number of osteopathic medical students
      continued to write of their desire for a change in the degree osteopathic medical
      colleges awarded. However, in July 2008 the AOA House of Delegates unanimously
      reaffirmed its commitment to continuing the traditional DO degree.

PMID- 24917637
TI  - Osteopathic approach to sacroiliac dysfunction in a patient with steroid
      myopathy: case report and literature review.
AB  - Long-term steroid use has a well-documented risk of myopathy that imposes
      functional limitations for patients and challenges for health care providers.
      Proximal weakness from steroid myopathy affects support structures around the
      pelvic girdle and likely predisposes patients to somatic dysfunction. To the
      authors' knowledge, there are no prior reports in the literature that describe an
      osteopathic manipulative medicine (OMM) approach for patients with steroid
      myopathy. In the present case report, a 59-year-old woman with acute myeloid
      leukemia received a blood stem cell transplantation and developed
      gastrointestinal graft-versus-host disease. High-dose steroids were prescribed,
      and she developed proximal weakness from steroid myopathy. The patient's acute
      inpatient rehabilitation was impacted by new onset left sacroiliac dysfunction. A
      patient-focused OMM approach was used to assist the patient in maximizing her
      sacroiliac function. The proximal weakness seen with steroid myopathy
      necessitates special considerations for an OMM approach to address somatic
      dysfunction associated with this disease.

PMID- 24917638
TI  - Hepatic cystic echinococcosis.

PMID- 24917639
TI  - Mendelian randomization studies in coronary artery disease.
AB  - Epidemiological research over the last 50 years has discovered a plethora of
      biomarkers (including molecules, traits or other diseases) that associate with
      coronary artery disease (CAD) risk. Even the strongest association detected in
      such observational research precludes drawing conclusions about the causality
      underlying the relationship between biomarker and disease. Mendelian
      randomization (MR) studies can shed light on the causality of associations, i.e
      whether, on the one hand, the biomarker contributes to the development of disease
      or, on the other hand, the observed association is confounded by unrecognized
      exogenous factors or due to reverse causation, i.e. due to the fact that
      prevalent disease affects the level of the biomarker. However, conclusions from a
      MR study are based on a number of important assumptions. A prerequisite for such
      studies is that the genetic variant employed affects significantly the biomarker
      under investigation but has no effect on other phenotypes that might confound the
      association between the biomarker and disease. If this biomarker is a true causal
      risk factor for CAD, genotypes of the variant should associate with CAD risk in
      the direction predicted by the association of the biomarker with CAD. Given a
      random distribution of exogenous factors in individuals carrying respective
      genotypes, groups represented by the genotypes are highly similar except for the
      biomarker of interest. Thus, the genetic variant converts into an unconfounded
      surrogate of the respective biomarker. This scenario is nicely exemplified for
      LDL cholesterol. Almost every genotype found to increase LDL cholesterol level by
      a sufficient amount has also been found to increase CAD risk. Pending a number of
      conditions that needed to be fulfilled by the genetic variant under investigation
      (e.g. no pleiotropic effects) and the experimental set-up of the study, LDL
      cholesterol can be assumed to act as the functional component that links
      genotypes and CAD risk and, more importantly, it can be assumed that any
      modulation of LDL cholesterol-by whatever mechanism-would have similar effects on
      disease risk. Therefore, MR analysis has tremendous potential for identifying
      therapeutic targets that are likely to be causal for CAD. This review article
      discusses the opportunities and challenges of MR studies for CAD, highlighting
      several examples that involved multiple biomarkers, including various lipid and
      inflammation traits as well as hypertension, diabetes mellitus, and obesity. 

PMID- 24917640
TI  - Cardiac involvement in relapsing polychondritis.

PMID- 24917641
TI  - Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review
      and meta-analysis.
AB  - AIM: Thrombolytic therapy induces faster clot dissolution than anticoagulation in
      patients with acute pulmonary embolism (PE) but is associated with an increased
      risk of haemorrhage. We reviewed the risks and benefits of thrombolytic therapy
      in the management of patients with acute PE. METHODS AND RESULTS: We
      systematically reviewed randomized controlled studies comparing systemic
      thrombolytic therapy plus anticoagulation with anticoagulation alone in patients
      with acute PE. Fifteen trials involving 2057 patients were included in our meta
      analysis. Compared with heparin, thrombolytic therapy was associated with a
      significant reduction of overall mortality (OR; 0.59, 95% CI: 0.36-0.96). This
      reduction was not statistically significant after exclusion of studies including
      high-risk PE (OR; 0.64, 95% CI: 0.35-1.17). Thrombolytic therapy was associated
      with a significant reduction in the combined endpoint of death or treatment
      escalation (OR: 0.34, 95% CI: 0.22-0.53), PE-related mortality (OR: 0.29; 95% CI:
      0.14-0.60) and PE recurrence (OR: 0.50; 95% CI: 0.27-0.94). Major haemorrhage
      (OR; 2.91, 95% CI: 1.95-4.36) and fatal or intracranial bleeding (OR: 3.18, 95%
      CI: 1.25-8.11) were significantly more frequent among patients receiving
      thrombolysis. CONCLUSIONS: Thrombolytic therapy reduces total mortality, PE
      recurrence, and PE-related mortality in patients with acute PE. The decrease in
      overall mortality is, however, not significant in haemodynamically stable
      patients with acute PE. Thrombolytic therapy is associated with an increase of
      major and fatal or intracranial haemorrhage.

PMID- 24917643
TI  - Optical coherence tomography images of iliac artery fibromuscular dysplasia.

PMID- 24917642
TI  - Mechanical alternans from an obstructive thrombosed prosthetic heart valve.

PMID- 24917644
TI  - Is our heart a well-designed pump? The heart along animal evolution.
AB  - A carrier system for gases and nutrients became mandatory when primitive animals
      grew larger and developed different organs. The first circulatory systems are
      peristaltic tubes pushing slowly the haemolymph into an open vascular tree
      without capillaries (worms). Arthropods developed contractile bulges on the
      abdominal aorta assisted by accessory hearts for wings or legs and by abdominal
      respiratory motions. Two-chamber heart (atrium and ventricle) appeared among
      mollusks. Vertebrates have a multi-chamber heart and a closed circulation with
      capillaries. Their heart has two chambers in fishes, three chambers (two atria
      and one ventricle) in amphibians and reptiles, and four chambers in birds and
      mammals. The ventricle of reptiles is partially divided in two cavities by an
      interventricular septum, leaving only a communication of variable size leading to
      a variable shunt. Blood pressure increases progressively from 15 mmHg (worms) to
      170/70 mmHg (birds) according to the increase in metabolic rate. When systemic
      pressure exceeds 50 mmHg, a lower pressure system appears for the circulation
      through gills or lungs in order to improve gas exchange. A four-chamber heart
      allows a complete separation of systemic and pulmonary circuits. This review
      describes the circulatory pumping systems used in the different classes of
      animals, their advantages and failures, and the way they have been modified with
      evolution. 

PMID- 24917645
TI  - Understanding IMPROVE-IT and the cardinal role of LDL-C lowering in CVD
      prevention.

PMID- 24917646
TI  - Atherosclerotic changes in coronary aneurysms post-Kawasaki disease: in vivo
      demonstration with near-infrared spectroscopy and intravascular ultrasound.

PMID- 24917647
TI  - Windlass Mechanism in Individuals With Diabetes Mellitus, Peripheral Neuropathy,
      and Low Medial Longitudinal Arch Height.
AB  - BACKGROUND: The windlass mechanism, acting through the plantar fascia, stabilizes
      the arches of the foot during stance phase of gait. The purpose of this study was
      to compare changes in radiographic measurements of the medial longitudinal arch
      (MLA) between toe-flat and -extended positions in participants with and without
      diabetes mellitus (DM), peripheral neuropathy (PN), and a low MLA. METHODS:
      Twelve participants with DMPN and low MLA and 12 controls received weightbearing
      radiographs in a toe-flat and toe-extended position. DMPN participants were
      subcategorized from radiographs into DMPN severe, evidence of severe joint
      changes, and DMPN low, absence of joint changes. Primary measurements of MLA were
      determined in each position and included Meary's angle, talar declination angle,
      first metatarsal declination angle, and navicular height. RESULTS: The DMPN
      severe group had no difference between toe-flat and -extended positions for
      Meary's, talar declination, and first metatarsal declination angles (P > .35)
      while navicular height elevated (P < .05). The DMPN low group had no difference
      between toe-flat and -extended positions for talar declination angle (P = .38),
      while Meary's angle, first metatarsal declination angle, and navicular height
      elevated (P < .05). All measurements in the control group changed, consistent
      with arch height elevation, when toes were extended (P < .05). CONCLUSION: The
      DMPN severe and low groups showed impaired ability to raise the arch from the toe
      flat to -extended position. Further research is needed to examine the
      contribution of specific windlass mechanism components (ie, plantar fascia,
      ligament, foot joint integrity, and mobility) as they relate to progressive foot
      deformity in adults with DMPN. LEVEL OF EVIDENCE: Level III, comparative series.

PMID- 24917648
TI  - Bone marrow-derived cells and biophysical stimulation for talar osteochondral
      lesions: a randomized controlled study.
AB  - BACKGROUND: Osteochondral lesions of the talus (OLT) frequently occur after ankle
      sprains in young patients participating in sports activities. These injuries may
      lead to chronic pain, joint swelling, and finally osteoarthritis, therefore,
      surgical repair is frequently needed. A collagen scaffold seeded with bone marrow
      derived cells (BMDCs) harvested from patient's iliac crest and implanted into the
      OLT through a single arthroscopic procedure has been recently proposed as an
      effective treatment option. Nevertheless, BMDCs, embedded in an inflammatory
      environment, tend to differentiate toward a fibroblast phenotype with a
      consequential loss of mechanical characteristics. Biophysical stimulation with
      pulsed electromagnetic fields (PEMFs) has been shown to promote anabolic
      chondrocyte activity, stimulate proteoglycan synthesis, and reduce the release of
      the most relevant pro-inflammatory cytokines. The aim of this randomized
      controlled trial was to evaluate the effects of PEMFs on clinical outcome in
      patients who underwent BMDCs transplantation for OLT. METHODS: Thirty patients
      affected by grade III and IV Outerbridge OLT underwent BMDCs transplantation.
      After surgery, patients were randomly assigned to either experimental group
      (PEMFs 4 hours per day for 60 days starting within 3 days after operation) or
      control group. Clinical outcome was evaluated with (American Orthopaedic Foot and
      Ankle Society) AOFAS score, Visual Analog Scale (VAS), and Short Form-36 (SF-36).
      RESULTS: Significantly higher AOFAS score was recorded in the experimental group
      both at 6 or 12 months follow-up. At 60 days and 6 and 12 months follow-up,
      significant lower pain was observed in the experimental group. No significant
      difference was found in SF-36 between groups. CONCLUSION: A superior clinical
      outcome was found in the experimental group with more than 10 points higher AOFAS
      score at final follow-up. Biophysical stimulation started soon after surgery
      aided patient recovery leading to pain control and a better clinical outcome with
      these improvements lasting more than 1 year after surgery. LEVEL OF EVIDENCE:
      Level II, prospective comparative study.

PMID- 24917649
TI  - Treatment for severe functional tricuspid regurgitation: annuloplasty versus
      valve replacement.
AB  - OBJECTIVES: Previous studies have compared the outcomes of mitral annuloplasty
      with those of mitral valve replacement in patients with functional mitral
      regurgitation. However, data comparing the results of tricuspid annuloplasty
      (TAP) with those of tricuspid valve replacement (TVR) in patients with functional
      tricuspid regurgitation (FTR) have been scarce. We evaluated whether TAP was an
      optimal option for severe FTR. METHODS: From 1996 to 2012, 175 patients (57 +/-
      11 years old) underwent surgical correction for severe FTR. A total of 108
      patients underwent TAP (the TAP group), and 67 underwent TVR (the TVR group).
      Inverse probability of treatment weighting (IPTW) analysis and propensity score
      matching with 37 patients in each group were performed to adjust for the baseline
      differences between the two groups. RESULTS: Early mortality occurred in 13
      patients without any inter-group differences. There were 35 late mortalities,
      including 24 cardiac deaths. The 5- and 10-year freedom rates from cardiac death
      were 93.0 and 88.5%, respectively, in the TAP group, and 84.7 and 69.8%,
      respectively, in the TVR group. The IPTW-adjusted multivariable analysis revealed
      that the freedom rates from cardiac death were higher in the TAP group than in
      the TVR group (P = 0.01). In the propensity score-matched patients, the freedom
      rates from cardiac death and tricuspid valve-related event were higher in the TAP
      group than in the TVR group, although the difference was not statistically
      significant. CONCLUSIONS: TAP should be considered as a treatment of choice for
      patients with severe FTR because TVR has been associated with long-term cardiac
      death and valve-related events.

PMID- 24917650
TI  - Biventricular assist device use in non-dilated hypertrophic cardiomyopathy.
AB  - Advanced heart failure is a rare but important complication of hypertrophic
      cardiomyopathy (HCM). The only definitive treatment is heart transplantation and
      the role of ventricular assist devices remains uncertain. We describe the use of
      implantable biventricular assist devices in the treatment of a patient with 'end
      stage' non-dilated HCM. 

PMID- 24917651
TI  - Evaluation of bioactive compounds of black mulberry juice after thermal,
      microwave, ultrasonic processing, and storage at different temperatures.
AB  - The effect of different sterilization methods (thermal, microwave, and ultrasonic
      processing) on the main bioactive compounds and antioxidant activity of black
      mulberry juice during selected storage time (8 days) and temperatures (5, 15, and
      25 C) was investigated. The antioxidant activity of thermal-treated juice
      depleted with storage time, whilst both ultrasound- and microwave-treated juices
      showed transient increase in antioxidant activity during the first 2 days that
      later decreased with storage time. Lower temperature storage preserved more
      bioactive compounds and antioxidant activity, especially in ultrasound sterilized
      samples. The activation energy values were 15.99, 13.07, and 12.81 kJ/mol for
      ultrasonic, microwave, and thermal pasteurization processes, respectively. In
      general, ultrasound-sterilized samples showed higher total phenolics,
      anthocyanin, and antioxidant activity compared to the microwave- and thermal
      processed juice during the storage time especially at lower temperatures. 

PMID- 24917652
TI  - Nuclear factor erythroid 2-related factor 2 rescues the oxidative stress induced
      by di-N-butylphthalate in testicular Leydig cells.
AB  - AIM: This study aimed to determine whether nuclear factor erythroid 2-related
      factor 2 antagonized the oxidative stress induced by di-N-butylphthalate (DBP) in
      testicular Leydig cells. METHODS: Mouse TM3 testicular Leydig cells were treated
      with Nrf2 knockdown (KD) or overexpression in the presence and absence of DBP.
      Oxidative profiles were examined. Nrf2 target antioxidant genes were studied, and
      the effects of Nrf2 inducer sulphoraphane (SFN) were tested. RESULTS: DBP induced
      intracellular oxidative stress to a similar extent with Nrf2 KD. Expression and
      protein levels of Nrf2 were increased together with its target genes, namely heme
      oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1
      and peroxiredoxin 6, following DBP stimulation. Use of SFN not only restored the
      intracellular oxidative toxicity but also cell proliferation and testosterone
      secretion in response to DBP. CONCLUSION: Increased Nrf2 activity, for example,
      by SFN can effectively antagonize the oxidative stress in testicular Leydig cells
      caused by DBP.

PMID- 24917653
TI  - Extensive investigation of 114 patients with Sheehan's syndrome: a continuing
      disorder.
AB  - OBJECTIVE: Sheehan's syndrome (SS) is a well-known cause of hypopituitarism
      resulting from postpartum pituitary necrosis. Because of its rarity in Western
      society, its diagnosis is often overlooked. We aimed to investigate the clinical,
      laboratory, and radiological aspects of SS in a large number of patients. STUDY
      DESIGN: A retrospective assessment of the medical records of 114 patients with SS
      was conducted. In addition, sella turcica volumes of 29 healthy women were
      compared with those of patients by magnetic resonance imaging examinations.
      RESULTS: The mean period of diagnostic delay was 19.7 years in patients with SS.
      It was found that 52.6% of patients had nonspecific complaints, 30.7% had
      complaints related to adrenal insufficiency, and 9.6% had complaints related to
      hypogonadism when diagnosed. At the time of diagnosis, 55.3% of the patients had
      panhypopituitarism, while 44.7% had partial hypopituitarism. The number of
      deficient hormones was found to be increased over the years. None of the patients
      whose basal prolactin was below 4.0 ng/ml had adequate prolactin responses to TRH
      test, while all patients whose basal prolactin was above 7.8 ng/ml had adequate
      responses. Mean sella volume was found to be significantly lower in the SS group
      (340.5+/-214 mm(3)) than that in the healthy group (602.5+/-192 mm(3)).
      CONCLUSIONS: SS is a common cause of hypopituitarism in underdeveloped and
      developing countries. The main reasons for diagnostic delay seem to be the high
      frequency of patients with nonspecific complaints and neglect of SS. In addition,
      the TRH stimulation test was found to have a high sensitivity and specificity to
      recognize PRL deficiency. Furthermore, small sella size may have an important
      contributing role in the etiopathogenesis of SS.

PMID- 24917654
TI  - Subclinical hypothyroidism represents an additional risk factor for coronary
      artery calcification, especially in subjects with intermediate and high
      cardiovascular risk scores.
AB  - OBJECTIVE: Several studies have suggested an association between subclinical
      hypothyroidism (SCH) and increased cardiovascular risk. The aim of this study was
      to evaluate the presence of coronary artery disease (CAD) in asymptomatic
      patients with SCH by measuring the coronary artery calcium score (CACS). DESIGN:
      A total of 222 asymptomatic subjects (103 SCH and 119 euthyroid (EU)), who were
      between the ages of 35 and 65 years and had no previous history of CAD, were
      enrolled for this cross-sectional analysis. METHODS: The criteria for SCH
      included a confirmed normal serum free thyroxine and high TSH levels. Lipid
      profile, Framingham risk score (FRS) and CACS analyses were performed for all
      subjects. RESULTS: The SCH and EU groups were comparable with respect to age,
      gender, BMI and frequency of diabetes, systemic arterial hypertension,
      hypercholesterolaemia and smoking. There was no difference in the median CACS
      between the SCH and EU groups. However, in the subgroup of subjects with
      intermediate/high FRS (AR10y >=10%), CACS was higher in the SCH subjects compared
      with EU subjects (EU vs SCH, 0.0 (57.0) vs 23.0 (161.5); P=0.045). Multivariate
      analysis revealed that the risk for CACS >100 was independently associated with
      male gender, age >55 years, and the presence of simultaneous SCH and AR10y >=10%
      (OR=87.5 (CI=2.1-3500); P=0.001). Serum TSH was positively correlated with CACS,
      especially in intermediate/high FRS subjects (rs=0.301, P=0.045). CONCLUSIONS: It
      was demonstrated that SCH represents an additional risk factor for CAD, notably
      in intermediate and high FRS subjects.

PMID- 24917655
TI  - Zinc oxide influences mitogen-activated protein kinase and TGF-beta1 signaling
      pathways, and enhances intestinal barrier integrity in weaned pigs.
AB  - Weaning is the most significant event in the life of pigs and is always related
      with intestinal disruption. Although it is well known that zinc oxide (ZnO)
      exerts beneficial effects on the intestinal barrier, the mechanisms underlying
      these effects have not yet been fully elucidated. We examined whether ZnO
      protects the intestinal barrier via mitogen-activated protein kinases and TGF
      beta1 signaling pathways. Twelve barrows weaned at 21 d of age were randomly
      assigned to two treatments (0 verus 2200 mg Zn/kg from ZnO) for 1 wk. The results
      showed that supplementation with ZnO increased daily gain and feed intake, and
      decreased postweaning scour scores. ZnO improved intestinal morphology, as
      indicated by increased villus height and villus height:crypt depth ratio, and
      intestinal barrier function, indicated by increased transepithelial electrical
      resistance and decreased mucosal-to-serosal permeability to 4-ku FITC dextran.
      ZnO decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK
      and p-p38/p38), while it increased the ratio of ERK (p-ERK/ERK). Supplementation
      with ZnO increased intestinal TGF-beta1 expression. The results indicate that
      supplementation with ZnO activates ERK 1/2, and inhibits JNK and p38 signaling
      pathways, and increases intestinal TGF-beta1 expression in weaned pigs.

PMID- 24917656
TI  - Heartland virus-associated death in tennessee.
AB  - BACKGROUND: Heartland virus (HRTV) is a tick-borne phlebovirus recently described
      in Missouri that is associated with fever, leukopenia, and thrombocytopenia. The
      virus has also been detected in Ambylomma americanum ticks. METHODS: Here we
      report the first fatal case of HRTV disease in an 80-year-old Tennessee resident.
      He was hospitalized with fever, confusion, leukopenia, and thrombocytopenia and
      developed multiorgan failure and hemorrhage. A tick-borne illness was suspected
      and testing for ehrlichiosis was negative. He died on hospital day 15, and
      autopsy specimens were tested for various pathogens as part of an unexplained
      death evaluation. RESULTS: HRTV antigens were detected in postmortem spleen and
      lymph nodes by immunohistochemistry, and HRTV was detected in premortem blood by
      reverse transcription polymerase chain reaction and by isolation in cell culture.
      CONCLUSIONS: This case demonstrates that HRTV infection can cause severe disease
      and death and expands the geographic range of HRTV within the United States.

PMID- 24917658
TI  - Staggered and tapered antibiotic withdrawal with administration of kefir for
      recurrent Clostridium difficile infection.
AB  - Daily administration of the probiotic kefir given in combination with a staggered
      and tapered antibiotic withdrawal regimen may resolve recurrent Clostridium
      difficile infection as effectively as fecal microbiota transplantation. 

PMID- 24917657
TI  - Effectiveness of 7-valent pneumococcal conjugate vaccine against invasive
      pneumococcal disease in HIV-infected and -uninfected children in south africa: a
      matched case-control study.
AB  - BACKGROUND: South Africa introduced 7-valent pneumococcal conjugate vaccine
      (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We
      estimated the effectiveness of >=2 PCV7 doses against invasive pneumococcal
      disease (IPD) in human immunodeficiency virus (HIV)-infected and -uninfected
      children. METHODS: IPD (pneumococcus identified from a normally sterile site)
      cases were identified through national laboratory-based surveillance. Specimens
      were serotyped by Quellung or polymerase chain reaction. Four controls, matched
      for age, HIV status, and hospital were sought for each case. Using conditional
      logistic regression, we calculated vaccine effectiveness (VE) as 1 minus the
      adjusted odds ratio for vaccination. RESULTS: From March 2010 through November
      2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine serotype) and 109 HIV
      infected (43 [39%] vaccine serotype) cases and 752 HIV-uninfected and 347 HIV
      infected controls aged >=16 weeks. Effectiveness of >=2 PCV7 doses against
      vaccine-serotype IPD was 74% (95% confidence interval [CI], 25%-91%) among HIV
      uninfected and -12% (95% CI, -449% to 77%) among HIV-infected children.
      Effectiveness of >=3 doses against vaccine-serotype IPD was 90% (95% CI, 14%-99%)
      among HIV-uninfected and 57% (95% CI, -371% to 96%) among HIV-infected children.
      Among HIV-exposed but -uninfected children, effectiveness of >=2 doses was 92%
      (95% CI, 47%-99%) against vaccine-serotype IPD. Effectiveness of >=2 doses
      against all-serotype multidrug-resistant IPD was 96% (95% CI, 62%-100%) among HIV
      uninfected children. CONCLUSIONS: A 2 + 1 PCV7 schedule was effective in
      preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed, uninfected
      children. This finding supports the World Health Organization recommendation for
      this schedule as an alternative to a 3-dose primary series among HIV-uninfected
      individuals.

PMID- 24917659
TI  - National estimates of healthcare utilization by individuals with hepatitis C
      virus infection in the United States.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a major public health problem in
      the United States. Although prior studies have evaluated the HCV-related
      healthcare burden, these studies examined a single treatment setting and did not
      account for the growing "baby boomer" population (individuals born during 1945
      1965). METHODS: Data from the National Ambulatory Medical Care Survey, the
      National Hospital Ambulatory Medical Care Survey, and the Nationwide Inpatient
      Sample were analyzed. We sought to characterize healthcare utilization by
      individuals infected with HCV in the United States, examining adult (>=18 years)
      outpatient, emergency department (ED), and inpatient visits among individuals
      with HCV diagnosis for the period 2001-2010. Key subgroups included persons born
      before 1945 (older), between 1945 and 1965 (baby boomer), and after 1965
      (younger). RESULTS: Individuals with HCV infection were responsible for >2.3
      million outpatient, 73 000 ED, and 475 000 inpatient visits annually. Persons in
      the baby boomer cohort accounted for 72.5%, 67.6%, and 70.7% of care episodes in
      these settings, respectively. Whereas the number of outpatient visits remained
      stable during the study period, inpatient admissions among HCV-infected baby
      boomers increased by >60%. Inpatient stays totaled 2.8 million days and cost >$15
      billion annually. Nonwhites, uninsured individuals, and individuals receiving
      publicly funded health insurance were disproportionately affected in all
      healthcare settings. CONCLUSIONS: Individuals with HCV infection are large users
      of outpatient, ED, and inpatient health services. Resource use is highest and
      increasing in the baby boomer generation. These observations illuminate the
      public health burden of HCV infection in the United States.

PMID- 24917660
TI  - Central nervous system syndromes in solid organ transplant recipients.
AB  - Solid organ transplant recipients have a high incidence of central nervous system
      (CNS) complications, including both focal and diffuse neurologic deficits. In the
      immunocompromised host, the initial clinical evaluation must focus on both life
      threatening CNS infections and vascular or anatomic lesions. The clinical signs
      and symptoms of CNS processes are modified by the immunosuppression required to
      prevent graft rejection. In this population, these etiologies often coexist with
      drug toxicities and metabolic abnormalities that complicate the development of a
      specific approach to clinical management. This review assesses the multiple risk
      factors for CNS processes in solid organ transplant recipients and establishes a
      timeline to assist in the evaluation and management of these complex patients. 

PMID- 24917661
TI  - The influence of ART on the treatment of Trichomonas vaginalis among HIV-infected
      women.
AB  - OBJECTIVE: Among women who are human immunodeficiency virus positive (HIV+), both
      prevalent and persistent infections with Trichomonas vaginalis (TV) are common.
      TV has been shown to increase vaginal shedding of HIV, which may influence HIV
      sexual and perinatal transmission, making prevention important. In 1 cohort of
      HIV+ women in Kenya, antiretroviral therapy (ART) use, mostly nevirapine based,
      was associated with lower cure rates of TV for single-dose therapy. Our goal was
      to repeat this study in a US-based cohort of HIV+/TV+ women and compare outcomes
      to those with multidose therapy. METHODS: A secondary data analysis was performed
      on a multicentered cohort of HIV+/TV+ women who were randomized to single-dose (2
      grams) or 7-day (500 mg twice daily) multidose metronidazole (MTZ) treatment.
      Test of cure visit, via culture, occurred 6-12 days after treatment completion.
      Information was collected on sex partner treatment and sexual exposures.
      Persistent TV infection rates were compared for women on ART at baseline vs not
      on ART. RESULTS: Of the 226 women included, those on ART had more treatment
      failures than women not on ART (24/146 [16.4%] vs 5/80 [6.3%]; P = .03). When
      stratified by treatment arm, more treatment failures were seen in the single-dose
      arm (17/73 [23.3%] vs 3/39 [7.7%]; P = .05) than in the multidose arm (7/73
      [9.6%] vs 2/41 [4.8%]; P = .39). CONCLUSIONS: ART usage was associated with a
      higher TV persistent infection rate among those receiving the single-dose
      treatment, but not the multidose, providing more evidence that multidose should
      be the preferred treatment for HIV+ women.

PMID- 24917662
TI  - Early initiation of combination antiretroviral therapy in HIV-1-infected newborns
      can achieve sustained virologic suppression with low frequency of CD4+ T cells
      carrying HIV in peripheral blood.
AB  - BACKGROUND: A human immunodeficiency virus type 1 (HIV-1)-infected infant started
      on combination antiretroviral therapy (cART) at 30 hours of life was recently
      reported to have no detectable plasma viremia after discontinuing cART. The
      current study investigated the impact of early cART initiation on measures of HIV
      1 reservoir size in HIV-1-infected children with sustained virologic suppression.
      METHODS: Children born to HIV-1-infected mothers and started on cART within 72
      hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1-specific
      cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and
      RNA, presence of replication-competent HIV-1, and HLA genotype were determined
      for HIV-1-infected children with sustained virologic suppression. RESULTS: Of 136
      cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved
      sustained virologic suppression, HIV serology, HIV-1-specific cell-mediated
      immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1
      DNA was not detected in enriched CD4(+) T cells of the 4 children (<2.6
      copies/10(6) CD4(+) T cells), whereas HIV-1 RNA was detected (19.5-130 copies/1.5
      ug RNA). No virion-associated HIV-1 RNA was detected following mitogenic
      stimulation of peripheral blood CD4(+) T cells (5.4-8.0 million CD4(+) T cells)
      in these 4 children, but replication competent virus was detected by quantitative
      co-culture involving a higher number of cells in 1 of 2 children tested (0.1
      infectious units/10(6) CD4(+) T cells). CONCLUSIONS: In perinatally HIV-1
      infected newborns, initiation of cART within 72 hours of birth may significantly
      reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to
      determine whether functional HIV cure can be achieved in such children.

PMID- 24917663
TI  - Ubiquitous myocardial extensions into the pulmonary artery demonstrated by
      integrated intracardiac echocardiography and electroanatomic mapping: changing
      the paradigm of idiopathic right ventricular outflow tract arrhythmias.
AB  - BACKGROUND: Idiopathic ventricular arrhythmias of left bundle branch block
      inferior axis morphology are usually localized to the right ventricular outflow
      tract (RVOT), presumably below the pulmonic valve (PV). However, the PV location
      is usually not confirmed by direct visualization. METHODS AND RESULTS:
      Intracardiac echocardiography was used to visualize and tag the PV annulus, which
      was then integrated with 3-dimensional voltage maps of the RVOT. Distances were
      measured from the furthest extent of myocardial signal (bipolar voltage >=1.5 mV)
      to the PV annulus. This was performed in 24 control patients and 24 prospective
      patients with RVOT arrhythmias. Myocardial signal beyond the PV was found in 92%
      of controls and 88% of RVOT arrhythmia patients (P=1.000). Average myocardial
      extension was further on the septal side than on the free wall side for control
      patients (5.6 mm; interquartile range [IQR], 3.6-7.7, versus 1.7 mm; IQR (-)0.1
      to (+)4.0; P=0.002) and RVOT arrhythmia patients (5.7 mm; IQR, 2.7-7.7, versus
      1.4 mm; IQR, (-)0.8 to (+)4.8; P=0.004). Eleven (46%) RVOT arrhythmia foci were
      localized beyond the valve in the pulmonary artery (median 8.2 mm above PV; IQR,
      6.6-10.3 mm); these locations were confirmed as supravalvular by direct
      intracardiac echocardiography visualization. CONCLUSIONS: Myocardial voltage
      extension into the pulmonary artery in humans is ubiquitous and can be
      demonstrated in vivo using 3-dimensional integrated intracardiac echocardiography
      to localize the PV. These extensions frequently serve as origins of presumed RVOT
      arrhythmias; intracardiac echocardiography localization of the PV allows
      reclassification of these as pulmonary arterial arrhythmias.

PMID- 24917664
TI  - Prevalence of unknown thyroid disorders in a Sardinian cohort.
AB  - OBJECTIVE: To assess thyroid function, the presence of thyroid antibodies, as
      well as the presence of goiter and/or nodules in subjects without a prior
      diagnosis of thyroid disorders, in a region with mild to moderate iodine
      deficiency. DESIGN AND METHODS: This cross-sectional study is based on data
      obtained from first and third visits of participants in the Sardinian survey. We
      performed two different analyses. In one, we assessed the prevalence of unknown
      thyroid dysfunctions among 6252 subjects who had a medical examination and blood
      collection for assays of thyrotropin, free thyroxine, and antibodies against
      thyroperoxidase (AbTPO) and against thyroglobulin (AbTG). In a second analysis,
      we evaluated the frequency of undiagnosed goiter and nodules among 3377 subjects
      who had a thyroid ultrasound scan. Subjects were excluded if they had a previous
      history of thyroid disorders or presence of goiter and/or nodules, or thyroid
      surgery, or if they were taking drugs that could impair thyroid function.
      RESULTS: We found a low prevalence of overt thyroid dysfunction (hyperthyroidism
      0.4% and hypothyroidism 0.7%). The rates of subclinical hypothyroidism and
      hyperthyroidism were 4.7 and 2.4% respectively. Almost 16% of participants were
      positive for at least one antibody and 5.2% for both AbTG and AbTPO. Nodules were
      detected in 17.4% of subjects and the prevalence of goiter was 22.1%.
      CONCLUSIONS: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and
      goiter were common in subjects living in a mild to moderate iodine-deficient
      area. In this community, thyroid disorders often go undetected and screening
      could be reasonable in subjects at a higher risk.

PMID- 24917665
TI  - Novel calmodulin mutations associated with congenital arrhythmia susceptibility.
AB  - BACKGROUND: Genetic predisposition to life-threatening cardiac arrhythmias such
      as congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic
      ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death
      in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2)
      have been associated with severe forms of LQTS and CPVT, with life-threatening
      arrhythmias occurring very early in life. Additional mutation-positive cases are
      needed to discern genotype-phenotype correlations associated with calmodulin
      mutations. METHODS AND RESULTS: We used conventional and next-generation
      sequencing approaches, including exome analysis, in genotype-negative LQTS
      probands. We identified 5 novel de novo missense mutations in CALM2 in 3 subjects
      with LQTS (p.N98S, p.N98I, p.D134H) and 2 subjects with clinical features of both
      LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or
      cardiac arrest) ranged from 1 to 9 years. Three of 5 probands had cardiac arrest
      and 1 of these subjects did not survive. The clinical severity among subjects in
      this series was generally less than that originally reported for CALM1 and CALM2
      associated with recurrent cardiac arrest during infancy. Four of 5 probands
      responded to beta-blocker therapy, whereas 1 subject with mutation p.Q136P died
      suddenly during exertion despite this treatment. Mutations affect conserved
      residues located within Ca(2+)-binding loops III (p.N98S, p.N98I) or IV (p.D132E,
      p.D134H, p.Q136P) and caused reduced Ca(2+)-binding affinity. CONCLUSIONS: CALM2
      mutations can be associated with LQTS and with overlapping features of LQTS and
      CPVT.

PMID- 24917666
TI  - Rapamycin and interleukin-1beta impair brain-derived neurotrophic factor
      dependent neuron survival by modulating autophagy.
AB  - The mammalian target of rapamycin (mTOR) pathway has multiple important
      physiological functions, including regulation of protein synthesis, cell growth,
      autophagy, and synaptic plasticity. Activation of mTOR is necessary for the many
      beneficial effects of brain-derived neurotrophic factor (BDNF), including
      dendritic translation and memory formation in the hippocampus. At present,
      however, the role of mTOR in BDNF's support of survival is not clear. We report
      that mTOR activation is necessary for BDNF-dependent survival of primary rat
      hippocampal neurons, as either mTOR inhibition by rapamycin or genetic
      manipulation of the downstream molecule p70S6K specifically blocked BDNF rescue.
      Surprisingly, however, BDNF did not promote neuron survival by up-regulating mTOR
      dependent protein synthesis or through mTOR-dependent suppression of caspase-3
      activation. Instead, activated mTOR was responsible for BDNF's suppression of
      autophagic flux. shRNA against the autophagic machinery Atg7 or Atg5 prolonged
      the survival of neurons co-treated with BDNF and rapamycin, suggesting that
      suppression of mTOR in BDNF-treated cells resulted in excessive autophagy.
      Finally, acting as a physiological analog of rapamycin, IL-1beta impaired BDNF
      signaling by way of inhibiting mTOR activation as follows: the cytokine induced
      caspase-independent neuronal death and accelerated autophagic flux in BDNF
      treated cells. These findings reveal a novel mechanism of BDNF neuroprotection;
      BDNF not only prevents apoptosis through inhibiting caspase activation but also
      promotes neuron survival through modulation of autophagy. This protection
      mechanism is vulnerable under chronic inflammation, which deregulates autophagy
      through impairing mTOR signaling. These results may be relevant to age-related
      changes observed in neurodegenerative diseases.

PMID- 24917667
TI  - Digoxin derivatives with enhanced selectivity for the alpha2 isoform of Na,K
      ATPase: effects on intraocular pressure in rabbits.
AB  - In the ciliary epithelium of the eye, the pigmented cells express the alpha1beta1
      isoform of Na,K-ATPase, whereas the non-pigmented cells express mainly the
      alpha2beta3 isoform of Na,K-ATPase. In principle, a Na,K-ATPase inhibitor with
      selectivity for alpha2 could effectively reduce intraocular pressure with only
      minimal local and systemic toxicity. Such an inhibitor could be applied topically
      provided it was sufficiently permeable via the cornea. Previous experiments with
      recombinant human alpha1beta1, alpha2beta1, and alpha3beta1 isoforms showed that
      the classical cardiac glycoside, digoxin, is partially alpha2-selective and also
      that the trisdigitoxose moiety is responsible for isoform selectivity. This led
      to a prediction that modification of the third digitoxose might increase alpha2
      selectivity. A series of perhydro-1,4-oxazepine derivatives of digoxin have been
      synthesized by periodate oxidation and reductive amination using a variety of R
      NH2 substituents. Several derivatives show enhanced selectivity for alpha2 over
      alpha1, close to 8-fold in the best case. Effects of topically applied cardiac
      glycosides on intraocular pressure in rabbits have been assessed by their ability
      to either prevent or reverse acute intraocular pressure increases induced by 4
      aminopyridine or a selective agonist of the A3 adenosine receptor. Two relatively
      alpha2-selective digoxin derivatives efficiently normalize the ocular
      hypertension, by comparison with digoxin, digoxigenin, or ouabain. This
      observation is consistent with a major role of alpha2 in aqueous humor production
      and suggests that, potentially, alpha2-selective digoxin derivatives could be of
      interest as novel drugs for control of intraocular pressure. 

PMID- 24917668
TI  - Modulation of triglyceride and cholesterol ester synthesis impairs assembly of
      infectious hepatitis C virus.
AB  - In hepatitis C virus infection, replication of the viral genome and virion
      assembly are linked to cellular metabolic processes. In particular, lipid
      droplets, which store principally triacylglycerides (TAGs) and cholesterol esters
      (CEs), have been implicated in production of infectious virus. Here, we examine
      the effect on productive infection of triacsin C and YIC-C8-434, which inhibit
      synthesis of TAGs and CEs by targeting long-chain acyl-CoA synthetase and acyl
      CoA:cholesterol acyltransferase, respectively. Our results present high
      resolution data on the acylglycerol and cholesterol ester species that were
      affected by the compounds. Moreover, triacsin C, which blocks both triglyceride
      and cholesterol ester synthesis, cleared most of the lipid droplets in cells. By
      contrast, YIC-C8-434, which only abrogates production of cholesterol esters,
      induced an increase in size of droplets. Although both compounds slightly reduced
      viral RNA synthesis, they significantly impaired assembly of infectious virions
      in infected cells. In the case of triacsin C, reduced stability of the viral core
      protein, which forms the virion nucleocapsid and is targeted to the surface of
      lipid droplets, correlated with lower virion assembly. In addition, the virus
      particles that were released from cells had reduced specific infectivity. YIC-C8
      434 did not alter the association of core with lipid droplets but appeared to
      decrease production of infectious virus particles, suggesting a block in virion
      assembly. Thus, the compounds have antiviral properties, indicating that
      targeting synthesis of lipids stored in lipid droplets might be an option for
      therapeutic intervention in treating chronic hepatitis C virus infection. 

PMID- 24917669
TI  - Genetic analysis of the structure and function of 7SK small nuclear
      ribonucleoprotein (snRNP) in cells.
AB  - The positive transcription elongation factor b (P-TEFb), comprised of cyclin
      dependent kinase 9 (CDK9) and cyclins T1 (CycT1) or T2 (CycT2), activates
      eukaryotic transcription elongation. In growing cells, P-TEFb exists in active
      and inactive forms. In the latter, it is incorporated into the 7SK small nuclear
      ribonucleoprotein, which contains hexamethylene bisacetamide-induced proteins
      (HEXIM) 1 or 2, La-related protein 7 (LaRP7), methyl phosphate capping enzyme,
      and 7SK small nuclear RNA (7SK). HEXIM1 inhibits the kinase activity of CDK9 via
      interactions between 7SK, HEXIM1, and CycT1. LaRP7 and methyl phosphate capping
      enzyme interact with 7SK independently of HEXIM1 and P-TEFb. To analyze genetic
      interactions between HEXIM1 and/or LaRP7 and 7SK using a cell-based system, we
      established artificial heterologous RNA tethering assays in which reporter gene
      expression depended on interactions between selected regions of 7SK and its
      cognate binding partners fused to a strong activator. This system enabled us to
      map the HEXIM1- and LaRP7- binding regions of 7SK. Assays with various mutant 7SK
      plasmid targets revealed that the 5'U-Ubulge and central loop of stem-loop I or
      RNA motif 3 of 7SK are required for transactivation, suggesting that HEXIM1 and
      CycT1 form a combinatorial binding surface for 7SK. Moreover, a region in HEXIM1
      C-terminal to its previously mapped RNA-binding motif was also required for
      interactions between HEXIM1 and 7SK. Finally, a tyrosine-to-alanine mutation in
      HEXIM1, which is critical for its inhibitory effect on CDK9, changed HEXIM1 into
      an activator. These cell-based assays elucidate this important aspect of
      transcription elongation in vivo.

PMID- 24917670
TI  - Bidirectional modulation of thermal and chemical sensitivity of TRPM8 channels by
      the initial region of the N-terminal domain.
AB  - TRPM8, a nonselective cation channel activated by cold, voltage, and cooling
      compounds such as menthol, is the principal molecular detector of cold
      temperatures in primary sensory neurons of the somatosensory system. The N
      terminal domain of TRPM8 consists of 693 amino acids, but little is known about
      its contribution to channel function. Here, we identified two distinct regions
      within the initial N terminus of TRPM8 that contribute differentially to channel
      activity and proper folding and assembly. Deletion or substitution of the first
      40 residues yielded channels with augmented responses to cold and menthol. The
      thermal threshold of activation of these mutants was shifted 2  degrees C to
      higher temperatures, and the menthol dose-response curve was displaced to lower
      concentrations. Site-directed mutagenesis screening revealed that single point
      mutations at positions Ser-26 or Ser-27 by proline caused a comparable increase
      in the responses to cold and menthol. Electrophysiological analysis of the S27P
      mutant revealed that the enhanced sensitivity to agonists is related to a
      leftward shift in the voltage dependence of activation, increasing the
      probability of channel openings at physiological membrane potentials. In
      addition, we found that the region encompassing positions 40-60 is a key element
      in the proper folding and assembly of TRPM8. Different deletions and mutations
      within this region rendered channels with an impaired function that are retained
      within the endoplasmic reticulum. Our results suggest a critical contribution of
      the initial region of the N-terminal domain of TRPM8 to thermal and chemical
      sensitivity and the proper biogenesis of this polymodal ion channel. 

PMID- 24917671
TI  - A primary role for disulfide formation in the productive folding of prokaryotic
      Cu,Zn-superoxide dismutase.
AB  - Enzymatic activation of Cu,Zn-superoxide dismutase (SOD1) requires not only
      binding of a catalytic copper ion but also formation of an intramolecular
      disulfide bond. Indeed, the disulfide bond is completely conserved among all
      species possessing SOD1; however, it remains obscure how disulfide formation
      controls the enzymatic activity of SOD1. Here, we show that disulfide formation
      is a primary event in the folding process of prokaryotic SOD1 (SodC) localized to
      the periplasmic space. Escherichia coli SodC was found to attain beta-sheet
      structure upon formation of the disulfide bond, whereas disulfide-reduced SodC
      assumed little secondary structure even in the presence of copper and zinc ions.
      Moreover, reduction of the disulfide bond made SodC highly susceptible to
      proteolytic degradation. We thus propose that the thiol-disulfide status in SodC
      controls the intracellular stability of this antioxidant enzyme and that the
      oxidizing environment of the periplasm is required for the enzymatic activation
      of SodC. 

PMID- 24917672
TI  - Ninjurin1 enhances the basal motility and transendothelial migration of immune
      cells by inducing protrusive membrane dynamics.
AB  - Ninjurin1 is involved in the pathogenesis of experimental autoimmune
      encephalomyelitis, an animal model of multiple sclerosis, by mediating leukocyte
      extravasation, a process that depends on homotypic binding. However, the precise
      regulatory mechanisms of Ninjurin1 during inflammation are largely undefined. We
      therefore examined the pro-migratory function of Ninjurin1 and its regulatory
      mechanisms in macrophages. Interestingly, Ninjurin1-deficient bone marrow-derived
      macrophages exhibited reduced membrane protrusion formation and dynamics,
      resulting in the impairment of cell motility. Furthermore, exogenous Ninjurin1
      was distributed at the membrane of filopodial structures in Raw264.7 macrophage
      cells. In Raw264.7 cells, RNA interference of Ninjurin1 reduced the number of
      filopodial projections, whereas overexpression of Ninjurin1 facilitated their
      formation and thus promoted cell motility. Ninjurin1-induced filopodial
      protrusion formation required the activation of Rac1. In Raw264.7 cells
      penetrating an MBEC4 endothelial cell monolayer, Ninjurin1 was localized to the
      membrane of protrusions and promoted their formation, suggesting that Ninjurin1
      induced protrusive activity contributed to transendothelial migration. Taking
      these data together, we conclude that Ninjurin1 enhances macrophage motility and
      consequent extravasation of immune cells through the regulation of protrusive
      membrane dynamics. We expect these findings to provide insight into the
      understanding of immune responses mediated by Ninjurin1. 

PMID- 24917673
TI  - Chromatin protein HP1 interacts with the mitotic regulator borealin protein and
      specifies the centromere localization of the chromosomal passenger complex.
AB  - Accurate mitosis requires the chromosomal passenger protein complex (CPC)
      containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates
      chromosome dynamics. However, the chromatin factors that specify the CPC to the
      centromere remain elusive. Here we show that borealin interacts directly with
      heterochromatin protein 1 (HP1) and that this interaction is mediated by an
      evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo
      shadow domain of HP1. This borealin-HP1 interaction recruits the CPC to the
      centromere and governs an activation of Aurora B kinase judged by phosphorylation
      of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the
      motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B
      activity. On the other hand, the localization of the CPC in the midzone is
      independent of the borealin-HP1 interaction, demonstrating the spatial
      requirement of HP1 in CPC localization to the centromere. These findings reveal a
      previously unrecognized but direct link between HP1 and CPC localization in the
      centromere and illustrate the critical role of borealin-HP1 interaction in
      orchestrating an accurate cell division.

PMID- 24917674
TI  - Constitutive nuclear expression of dentin matrix protein 1 fails to rescue the
      Dmp1-null phenotype.
AB  - Dentin matrix protein 1 (DMP1) plays multiple roles in bone, tooth, phosphate
      homeostasis, kidney, salivary gland, reproductive cycles, and the development of
      cancer. In vitro studies have indicated two different biological mechanisms: 1)
      as a matrix protein, DMP1 interacts with alphavbeta3 integrin and activates MAP
      kinase signaling; and 2) DMP1 serves as a transcription co-factor. In vivo
      studies have demonstrated its key role in osteocytes. This study attempted to
      determine whether DMP1 functions as a transcription co-factor and regulates
      osteoblast functions. For gene expression comparisons using adenovirus
      constructs, we targeted the expression of DMP1 either to the nucleus only by
      replacing the endogenous signal peptide with a nuclear localization signal (NLS)
      sequence (referred to as (NLS)DMP1) or to the extracellular matrix as the WT type
      (referred to as (SP)DMP1) in MC3T3 osteoblasts. High levels of DMP1 in either
      form greatly increased osteogenic gene expression in an identical manner.
      However, the targeted (NLS)DMP1 transgene driven by a 3.6-kb rat Col 1alpha1
      promoter in the nucleus of osteoblasts and osteocytes failed to rescue the
      phenotyope of Dmp1-null mice, whereas the (SP)DMP1 transgene rescued the rickets
      defect. These studies support the notion that DMP1 functions as an extracellular
      matrix protein, rather than as a transcription co-factor in vivo. We also show
      that DMP1 continues its expression in osteoblasts during postnatal development
      and that the deletion of Dmp1 leads to an increase in osteoblast proliferation.
      However, poor mineralization in the metaphysis indicates a critical role for DMP1
      in both osteoblasts and osteocytes. 

PMID- 24917676
TI  - Novel cartilage oligomeric matrix protein (COMP) neoepitopes identified in
      synovial fluids from patients with joint diseases using affinity chromatography
      and mass spectrometry.
AB  - To identify patients at risk for progressive joint damage, there is a need for
      early diagnostic tools to detect molecular events leading to cartilage
      destruction. Isolation and characterization of distinct cartilage oligomeric
      matrix protein (COMP) fragments derived from cartilage and released into synovial
      fluid will allow discrimination between different pathological conditions and
      monitoring of disease progression. Early detection of disease and processes in
      the tissue as well as an understanding of the pathologic mechanisms will also
      open the way for novel treatment strategies. Disease-specific COMP fragments were
      isolated by affinity chromatography of synovial fluids from patients with
      rheumatoid arthritis, osteoarthritis, or acute trauma. Enriched COMP fragments
      were separated by SDSPAGE followed by in-gel digestion and mass spectrometric
      identification and characterization.Using the enzymes trypsin, chymotrypsin, and
      Asp-N for the digestions, an extensive analysis of the enriched fragments could
      be accomplished. Twelve different neoepitopes were identified and characterized
      within the enriched COMP fragments. For one of the neoepitopes, Ser77, an
      inhibition ELISA was developed. This ELISA quantifies COMP fragments clearly
      distinguishable from total COMP. Furthermore, fragments containing the neoepitope
      Ser77 were released into the culture medium of cytokine (TNF-alpha and IL
      6/soluble IL-6 receptor)-stimulated human cartilage explants. The identified
      neoepitopes provide a complement to the currently available commercial assays for
      cartilage markers. Through neoepitope assays, tools to pinpoint disease
      progression, evaluation methods for therapy, and means to elucidate disease
      mechanisms will be provided.

PMID- 24917675
TI  - Lipocalin 2 regulates brown fat activation via a nonadrenergic activation
      mechanism.
AB  - In this study, we report that lipocalin 2 (Lcn2), a recently characterized
      adipokine/cytokine, is a novel regulator of brown adipose tissue (BAT) activation
      by modulating the adrenergic independent p38 MAPK-PGC-1alpha-UCP1 pathway. Global
      Lcn2 knock-out (Lcn2(-/-)) mice have defective BAT thermogenic activation caused
      by cold stimulation and decreased BAT activity under high fat diet-induced
      obesity. Nevertheless, Lcn2(-/-) mice maintain normal sympathetic nervous system
      activation as evidenced by normal catecholamine release and lipolytic activity in
      response to cold stimulation. Further studies showed that Lcn2 deficiency impairs
      peroxisomal and mitochondrial oxidation of lipids and attenuates cold-induced
      Pgc1a and Ucp1 expression and p38 MAPK phosphorylation in BAT. Moreover, in vitro
      studies showed that Lcn2 deficiency reduces the thermogenic activity of brown
      adipocytes. Lcn2(-/-) differentiated brown adipocytes have significantly
      decreased expression levels of brown fat markers, decreased p38 MAPK
      phosphorylation, and decreased mitochondrial oxidation capacity. However, Lcn2(-/
      ) brown adipocytes have normal norepinephrine-stimulated p38 MAPK and hormone
      sensitive lipase phosphorylation and Pgc1a and Ucp1 expression, suggesting an
      intact beta-adrenergic signaling activation. More intriguingly, recombinant Lcn2
      was able to significantly stimulate p38 MAPK phosphorylation in brown adipocytes.
      Activating peroxisome proliferator-activated receptor gamma, a downstream
      effector of PGC-1alpha, by thiazolidinedione administration fully reverses the
      BAT function of Lcn2(-/-) mice. Our findings provide evidence for the novel role
      Lcn2 plays in oxidative metabolism and BAT activation via an adrenergic
      independent mechanism. 

PMID- 24917677
TI  - The bifunctional protein TtFARAT from Tetrahymena thermophila catalyzes the
      formation of both precursors required to initiate ether lipid biosynthesis.
AB  - The biosynthesis of ether lipids and wax esters requires as precursors fatty
      alcohols, which are synthesized by fatty acyl reductases (FARs). The presence of
      ether glycerolipids as well as branched wax esters has been reported in several
      free-living ciliate protozoa. In the genome of Tetrahymena thermophila, the only
      ORF sharing similarities with FARs is fused to an acyltransferase-like domain,
      whereas, in most other organisms, FARs are monofunctional proteins of similar
      size and domain structure. Here, we used heterologous expression in plant and
      yeast to functionally characterize the activities catalyzed by this protozoan
      protein. Transient expression in tobacco epidermis of a truncated form fused to
      the green fluorescence protein followed by confocal microscopy analysis suggested
      peroxisomal localization. In vivo approaches conducted in yeast indicated that
      the N-terminal FAR-like domain produced both 16:0 and 18:0 fatty alcohols,
      whereas the C-terminal acyltransferase-like domain was able to rescue the lethal
      phenotype of the yeast double mutant gat1Delta gat2Delta. Using in vitro
      approaches, we further demonstrated that this domain is a dihydroxyacetone
      phosphate acyltransferase that uses preferentially 16:0-coenzyme A as an acyl
      donor. Finally, coexpression in yeast with the alkyl-dihydroxyacetone phosphate
      synthase from T. thermophila resulted the detection of various glycerolipids with
      an ether bond, indicating reconstitution of the ether lipid biosynthetic pathway.
      Together, these results demonstrate that this FAR-like protein is peroxisomal and
      bifunctional, providing both substrates required by alkyl-dihydroxyacetone
      phosphate synthase to initiate ether lipid biosynthesis. 

PMID- 24917678
TI  - Stoichiometry of site-specific lysine acetylation in an entire proteome.
AB  - Acetylation of lysine epsilon-amino groups influences many cellular processes and
      has been mapped to thousands of sites across many organisms. Stoichiometric
      information of acetylation is essential to accurately interpret biological
      significance. Here, we developed and employed a novel method for directly
      quantifying stoichiometry of site-specific acetylation in the entire proteome of
      Escherichia coli. By coupling isotopic labeling and a novel pairing algorithm,
      our approach performs an in silico enrichment of acetyl peptides, circumventing
      the need for immunoenrichment. We investigated the function of the sole NAD(+)
      dependent protein deacetylase, CobB, on both site-specific and global
      acetylation. We quantified 2206 peptides from 899 proteins and observed a wide
      distribution of acetyl stoichiometry, ranging from less than 1% up to 98%.
      Bioinformatic analysis revealed that metabolic enzymes, which either utilize or
      generate acetyl-CoA, and proteins involved in transcriptional and translational
      processes displayed the highest degree of acetylation. Loss of CobB led to
      increased global acetylation at low stoichiometry sites and induced site-specific
      changes at high stoichiometry sites, and biochemical analysis revealed altered
      acetyl-CoA metabolism. Thus, this study demonstrates that sirtuin deacetylase
      deficiency leads to both site-specific and global changes in protein acetylation
      stoichiometry, affecting central metabolism. 

PMID- 24917679
TI  - A proton wire and water channel revealed in the crystal structure of isatin
      hydrolase.
AB  - The high resolution crystal structures of isatin hydrolase from Labrenzia
      aggregata in the apo and the product state are described. These are the first
      structures of a functionally characterized metal-dependent hydrolase of this
      fold. Isatin hydrolase converts isatin to isatinate and belongs to a novel family
      of metalloenzymes that include the bacterial kynurenine formamidase. The product
      state, mimicked by bound thioisatinate, reveals a water molecule that bridges the
      thioisatinate to a proton wire in an adjacent water channel and thus allows the
      proton released by the reaction to escape only when the product is formed. The
      functional proton wire present in isatin hydrolase isoform b represents a unique
      catalytic feature common to all hydrolases is here trapped and visualized for the
      first time. The local molecular environment required to coordinate thioisatinate
      allows stronger and more confident identification of orthologous genes encoding
      isatin hydrolases within the prokaryotic kingdom. The isatin hydrolase
      orthologues found in human gut bacteria raise the question as to whether the
      indole-3-acetic acid degradation pathway is present in human gut flora. 

PMID- 24917680
TI  - RNA polymerase III accurately initiates transcription from RNA polymerase II
      promoters in vitro.
AB  - In eukaryotes, there are three major RNA polymerases (Pol) in the nucleus, which
      are commonly described as transcribing non-overlapping subsets of genes.
      Structural studies have highlighted a conserved core shared among all three
      transcription systems. Initiation of human Pol III from TATA box-containing Pol
      II promoters under conditions with impaired Pol II transcription activity have
      been described previously. RNA polymerase III and Pol II were found to co
      localize at the promoters of the c-myc gene and the RPPH1 sRNA in vivo. Here, I
      report that Pol III can, like Pol II, initiate transcription from most tested Pol
      II core promoters when assayed with crude human nuclear extracts (HSK, SNF, or
      Dignam). Both polymerases often initiate from the same transcription start site,
      and depend on a TATA box or AT-rich region but not the downstream promoter
      element (DPE) or the motif ten element (MTE). Moderate (~2-fold) changes in the
      ratio of DNA template to nuclear extract were sufficient to change Pol II
      mediated transcription to a mixture of Pol II- and Pol III-, or to a solely Pol
      III-dependent initiation of transcription from Pol II promoters. Polymerase
      specificity is thus not fixed but a variable that depends on the properties of
      the promoter and the transcription conditions. These findings provide functional
      evidence for a close similarity between the Pol II and Pol III transcription
      complexes, and additionally explain previous controversies in the literature. 

PMID- 24917682
TI  - Macromolecular crowding decelerates aggregation of a beta-rich protein, bovine
      carbonic anhydrase: a case study.
AB  - The majority of in vitro investigations concerning protein aggregation have been
      performed in dilute systems, which poorly reflect the crowded in vivo scenario.
      Cell interior is highly crowded with soluble and insoluble macromolecules that
      alter macromolecular properties. Macromolecular crowding is known to enhance the
      rate and/or extent of protein aggregation. However, most of the understandings
      were derived from studies with alpha-rich or predominantly alpha-proteins.
      Indeed, alpha-proteins fold faster than beta-proteins and conversion of alpha
      helices to cross beta-sheets are responsible for aggregate/amyloid formation.
      Therefore, it is important to investigate how macromolecular crowding affects the
      aggregation propensity of beta-rich proteins. In this study, we investigated the
      effect of synthetic macromolecular crowders on bovine carbonic anhydrase (BCA, a
      beta-rich protein) aggregation. In contrast to the effect of macromolecular
      crowding on alpha-rich proteins, BCA aggregation was observed to be reduced due
      to decrease in the population of aggregation-prone intermediates as a consequence
      of increased native state stability. In addition, the extent of aggregation was
      found to depend on the nature of the crowder under consideration. Combining the
      published data on alpha-proteins and this study, we conclude that macromolecular
      crowding can have opposite consequences on protein aggregation process depending
      on the fold type of the protein. 

PMID- 24917681
TI  - Mechanism of ATPase-mediated Cu+ export and delivery to periplasmic chaperones:
      the interaction of Escherichia coli CopA and CusF.
AB  - Cellular copper homeostasis requires transmembrane transport and compartmental
      trafficking while maintaining the cell essentially free of uncomplexed Cu(2+/+).
      In bacteria, soluble cytoplasmic and periplasmic chaperones bind and deliver
      Cu(+) to target transporters or metalloenzymes. Transmembrane Cu(+)-ATPases
      couple the hydrolysis of ATP to the efflux of cytoplasmic Cu(+). Cytosolic Cu(+)
      chaperones (CopZ) interact with a structural platform in Cu(+)-ATPases (CopA) and
      deliver copper into the ion permeation path. CusF is a periplasmic Cu(+)
      chaperone that supplies Cu(+) to the CusCBA system for efflux to the
      extracellular milieu. In this report, using Escherichia coli CopA and CusF,
      direct Cu(+) transfer from the ATPase to the periplasmic chaperone was observed.
      This required the specific interaction of the Cu(+)-bound form of CopA with apo
      CusF for subsequent metal transfer upon ATP hydrolysis. As expected, the reverse
      Cu(+) transfer from CusF to CopA was not observed. Mutation of CopA extracellular
      loops or the electropositive surface of CusF led to a decrease in Cu(+) transfer
      efficiency. On the other hand, mutation of Met and Glu residues proposed to be
      part of the metal exit site in the ATPase yielded enzymes with lower turnover
      rates, although Cu(+) transfer was minimally affected. These results show how
      soluble chaperones obtain Cu(+) from transmembrane transporters. Furthermore, by
      explaining the movement of Cu(+) from the cytoplasmic pool to the extracellular
      milieu, these data support a mechanism by which cytoplasmic Cu(+) can be
      precisely directed to periplasmic targets via specific transporter-chaperone
      interactions. 

PMID- 24917683
TI  - Changes in muscle damage markers in female basketball players.
AB  - The aim of the present study was to investigate changes in muscle soreness, blood
      muscle damage markers, muscle strength and agility following an official
      basketball match. Eleven elite female professional basketball players (27.4 +/-
      4.8 years, 179.5 +/- 5.5 cm, 72.0 +/- 7.8 kg) of a team participated in this
      study. The official match was the seventh match of the season in the first phase
      of the Brazilian National Female Basketball Championship. Muscle soreness, plasma
      creatine kinase activity (CK), and myoglobin concentration (Mb) were determined
      before and after the match (post-match, 24 and 48 hours after the match). The 1RM
      strength for bench press and leg press, and the agility T test were assessed
      before and at 24 and 48 hours after the match. Significant increases in muscle
      soreness, CK and Mb were observed at 24 and 48 hours post-match (p<0.05). No
      significant changes in the 1RM strength and T test were detected during recovery
      (24 and 48 hours after the match). These results suggest that a basketball match
      induced limited muscle damage with minimal effect on performance during recovery.
      The small increase in muscle damage markers following a basketball match did not
      affect strength and agility performance. 

PMID- 24917684
TI  - The effects of single versus repeated plyometrics on landing biomechanics and
      jumping performance in men.
AB  - The aim of this study was to examine the chronic effects of single and repeated
      jumps training on vertical landing force (VGRF) and jump height in untrained men.
      The VGRF and jump height were compared after a six-week plyometric training
      programme containing single and repeated jumps, together with two additional
      parameters: landing time (LT) and range of the knee flexion during landing (KF).
      Thirty-six untrained physical education students with a plyometric training
      background were randomly assigned to a single jump group (SJG, n =12), repeated
      jumps group (RJG, n =12), and control group (CON, n =12). The SJG performed only
      single jumps, the RJG executed repeated (consecutive) jumps, whereas the CON did
      not perform any exercises at all. A countermovement jump (CMJ), repeated
      countermovement jumps (RCMJ), and a drop jump (DJ) were tested before and after
      the training. Only the RJG showed a significantly reduced VGRF (p < 0.05) in all
      tests. Both plyometric groups significantly improved (p < 0.05) their jump height
      in all tests. The LT was significantly greater in the RJG, compared to the SJG,
      in all tests. The KF was also significantly (p < 0.05) greater in the RJG than in
      the SJG for CMJ and RCMJ. The results suggest that repeated jumps are beneficial
      for simultaneous landing force reduction and jumping performance enhancement. 

PMID- 24917685
TI  - Is gnb3 c825t polymorphism associated with elite status of polish athletes?
AB  - The GNB3 gene encodes the beta 3 subunit of heterotrimeric G-proteins that are
      key components of intracellular signal transduction between G protein-coupled
      receptors (GPCR) and intracellular effectors and might be considered as a
      potential candidate gene for physical performance. OBJECTIVES: The aim of this
      study was to compare frequency distribution of the common C to T polymorphism at
      position 825 (C825T) of the GNB3 gene between athletes and nonathletic controls
      of the Polish population as well as to compare the genotype distribution and
      allele frequency of C825T variants within a group of athletes, i.e. between
      athletes of sports of different metabolic demands and competitive levels.
      METHODS: The study was performed in a group of 223 Polish athletes of the highest
      nationally competitive standard (123 endurance-oriented athletes and 100
      strength/ power athletes). Control samples were prepared from 354 unrelated,
      sedentary volunteers. RESULTS: The chi(2) test revealed no statistical
      differences between the endurance-oriented athletes and the control group or
      between sprint/strength athletes and the control group across the GNB3 825C/T
      genotypes. There were no male-female genotype or allele frequency differences in
      controls or in either strength/power or endurance-oriented athletes. No
      statistically significant differences in either allele frequencies or genotype
      distribution were noted between the top-elite, elite or sub-elite of endurance
      oriented and strength/power athletes and the control group. CONCLUSIONS: No
      association between elite status of Polish athletes and the GNB3 C825T
      polymorphic site has been found.

PMID- 24917686
TI  - Muscle damage after a tennis match in young players.
AB  - The present study investigated changes in indirect markers of muscle damage
      following a simulated tennis match play using nationally ranked young (17.6 +/-
      1.4 years) male tennis players. Ten young athletes played a 3-hour simulated
      match play on outdoor red clay courts following the International Tennis
      Federation rules. Muscle soreness, plasma creatine kinase activity (CK), serum
      myoglobin concentration (Mb), one repetition maximum (1RM) squat strength, and
      squat jump (SJ) and counter movement jump (CMJ) heights were assessed before,
      immediately after, and 24 and 48 h after the simulated match play. All parameters
      were also evaluated in a non-exercised group (control group). A small increase in
      the indirect markers of muscle damage (muscle soreness, CK and Mb) was detected
      at 24-48 hours post-match (p < 0.05). A marked acute decrement in neuromuscular
      performance (1RM squat strength: -35.2 +/- 10.4%, SJ: -7.0 +/- 6.0%, CMJ: -10.0
      +/- 6.3%) was observed immediately post-match (p < 0.05). At 24 h post-match, the
      1RM strength and jump heights were not significantly different from the baseline
      values. However, several players showed a decrease of these measures at 24 h
      after the match play. The simulated tennis match play induced mild muscle damage
      in young players. Coaches could monitor changes in the indirect markers of muscle
      damage to assess athletes' recovery status during training and competition. 

PMID- 24917687
TI  - Relationships between heart rate and physiological parameters of performance in
      top-level water polo players.
AB  - The aim of this study was to measure the heart rate (HR) response of eight elite
      water polo players during the four 7-min quarters of the game and to check for
      relationships with the physiological parameters of performance ([Formula: see
      text]O2max, Th1vent, Th2vent). Each athlete performed a [Formula: see text]O2max
      treadmill test and played a water polo game wearing a heart rate monitor. The
      game fatigue index was calculated as the ratio of the fourth-quarter HR to the
      first-quarter HR: HR4/HR1. The results showed a slight decrease in fourth-quarter
      HR compared with the first quarter, with the mean four-quarter HR equal to 79.9+/
      4.2% of HRmax. Stepwise multiple regression analysis showed [Formula: see
      text]O2max to be the main explanatory factor of game intensity, i.e. game HR
      expressed in %HRreserve (R=0.88, P<0.01). We observed that higher aerobic
      capacity resulted in higher game intensity. We also observed a decrease in the
      playing intensity in the fourth quarter compared with the first, likely due to
      very high game involvement. We concluded that high aerobic capacity seems
      necessary to ensure high game intensity in water polo. This suggests that coaches
      should encourage their athletes to reach a minimum level of [Formula: see
      text]O2max and that HR monitoring could be of great interest in the control of
      water polo training sessions. 

PMID- 24917688
TI  - Physiological and leukocyte subset responses to exercise and cold exposure in
      cold-acclimatized skaters.
AB  - We investigated physiological responses and changes in circulating immune cells
      following exercise in cold and thermoneutral conditions. Participants were short
      track skaters (n=9) who were acclimatized to cold conditions, and inline skaters
      (n=10) who were not acclimatized. All skaters were young, and skating at a
      recreational level three days per week for at least one year. Using a cross-over
      design, study variables were measured during 60 min of submaximal cycling (65%
      [Formula: see text]O2max) in cold (ambient temperature: 5+/-1 degrees C, relative
      humidity: 41+/-9%) and thermoneutral conditions (ambient temperature: 21+/-1
      degrees C, relative humidity: 35+/-5%). Heart rate, blood lactate and tympanic
      temperature were measured at rest, during exercise and recovery. Plasma cortisol,
      calprotectin and circulating blood cell numbers were measured before and after 60
      min of cold or thermoneutral conditions, and during recovery from exercise. Heart
      rate was lower in both groups during exercise in cold versus thermoneutral
      conditions (P<0.05). The increase in total leukocytes during recovery was
      primarily due to an increase in neutrophils in both groups. The cold-acclimatized
      group activated neutrophils after exercise in cold exposure, whereas the non
      acclimatized group activated lymphocyte and cortisol after exercise in cold
      exposure. Lymphocyte subsets significantly changed in both groups over time
      during recovery as compared to rest. Immediately after exercise in both groups,
      CD16+ and CD69+ cells were elevated compared to rest or before exercise in both
      conditions. Acclimatization to exercise in the cold does not appear to influence
      exercise-induced immune changes in cold conditions, with the possible exception
      of neutrophils, lymphocytes and cortisol concentration. 

PMID- 24917689
TI  - Urinary creatine at rest and after repeated sprints in athletes: a pilot study.
AB  - Creatine plays a key role in muscle function and its evaluation is important in
      athletes. In this study, urinary creatine concentration was measured in order to
      highlight its possible significance in monitoring sprinters. The study included
      51 sprinters and 25 age- and sex-matched untrained subjects as a control group.
      Body composition was measured and dietary intake estimated. Urine samples were
      collected before and after standardized physical exercise. Creatine was assessed
      by gas chromatography mass spectrometry. Basal urinary creatine (UC) was
      significantly lower in sprinters than controls (34+/-30 vs. 74+/-3 umol/mmol
      creatinine, p < 0.05). UC was inversely correlated with body mass (r = -0.34, p <
      0.01) and lean mass (r = -0.30, p < 0.05), and positively correlated with fat
      mass (r = 0.32, p < 0.05). After acute exercise, urinary creatine significantly
      decreased in both athletes and controls. UC is low in sprinters at rest and
      further decreases after exercise, most likely due to a high uptake and use of
      creatine by muscles, as muscle mass and physical activity are supposed to be
      greater in athletes than untrained subjects. Further studies are needed to test
      the value of urinary creatine as a non-invasive marker of physical condition and
      as a parameter for managing Cr supplementation in athletes. 

PMID- 24917690
TI  - Reliability and validity of an accele-rometric system for assessing vertical
      jumping performance.
AB  - The validity of an accelerometric system (Myotest(c)) for assessing vertical jump
      height, vertical force and power, leg stiffness and reactivity index was
      examined. 20 healthy males performed 3*"5 hops in place", 3*"1 squat jump" and 3*
      "1 countermovement jump" during 2 test-retest sessions. The variables were
      simultaneously assessed using an accelerometer and a force platform at a
      frequency of 0.5 and 1 kHz, respectively. Both reliability and validity of the
      accelerometric system were studied. No significant differences between test and
      retest data were found (p < 0.05), showing a high level of reliability. Besides,
      moderate to high intraclass correlation coefficients (ICCs) (from 0.74 to 0.96)
      were obtained for all variables whereas weak to moderate ICCs (from 0.29 to 0.79)
      were obtained for force and power during the countermovement jump. With regards
      to validity, the difference between the two devices was not significant for 5
      hops in place height (1.8 cm), force during squat (-1.4 N . kg(-1)) and
      countermovement (0.1 N . kg(-1)) jumps, leg stiffness (7.8 kN . m(-1)) and
      reactivity index (0.4). So, the measurements of these variables with this
      accelerometer are valid, which is not the case for the other variables. The main
      causes of non-validity for velocity, power and contact time assessment are
      temporal biases of the takeoff and touchdown moments detection. 

PMID- 24917691
TI  - Quercetin effects on weight gain and caloric intake in exercised rats.
AB  - Quercetin is a flavonoid which activates oxidative metabolism. Quercetin may
      reduce weight gain by decreasing feed efficiency. The present study aims to
      evaluate weight gain, caloric intake and feed efficiency in exercised and
      sedentary rats supplemented with quercetin. Wistar rats were divided into four
      groups: quercetin-exercise training (QT), quercetin-sedentary (QS), placebo
      exercise training (PT) and placebo-sedentary (PS). Rats were exercised and/or
      orally supplemented with quercetin (25 mg . kg(-1) on alternate days) during six
      weeks. Weight gain of the QT group decreased when compared with the PT and PS
      groups. Exercised groups increased cumulative caloric intake during the
      experimental period. The QT group rats also reduced their feed efficiency when
      compared with the QS and PS groups. These results suggest that quercetin is not
      able to decrease weight gain because no differences were found between placebo
      and quercetin condition either in the sedentary or in the training condition. 

PMID- 24917692
TI  - Nigari (deep seawater concentrate) enhances the treadmill exercise performance of
      gerbils.
AB  - The beneficial effect of magnesium supplementation on exercise performance has
      been reported by many researchers. In the present study, the effect of nigari, a
      concentrate of deep seawater containing high magnesium levels, on exercise
      performance, was examined. Gerbils were given double-distilled water or nigari
      (18 mg . kg(-1), po) orally 30 min before exercise. All animals were subjected to
      forced exercise on a treadmill for 90 min at three successive speeds of 10, 15,
      and 20 m . min(-1). The retention numbers were recorded. The retention numbers
      were 85.0 +/- 21.0, 46.0 +/- 9.7, and 48.0 +/- 14.2 in the control group, and
      44.0 +/- 10.9, 23.0 +/- 8.4, and 13.0 +/- 4.8 in the nigari-treated group at the
      three speeds, respectively. The retention numbers were significantly reduced at
      higher speeds (by 50% at 15 and 73% at 20 m . min(-1), respectively) in the
      nigari-treated group when compared to those of the control group, respectively.
      Thus, nigari administration appeared to reduce retention numbers and enhance
      exercise performance in gerbils. 

PMID- 24917694
TI  - Plagiarism: an academic offence.
AB  - How to cite the article: Bijle MN, Patil S. Plagiarism: An Academic Offence. J
      Int Oral Health 2014;6(2):i. 

PMID- 24917693
TI  - Imaging and modeling of flow in porous media using clinical nuclear emission
      tomography systems and computational fluid dynamics.
AB  - This paper presents experimental and modeling aspects of applying nuclear
      emission tomography to study fluid flow in laboratory packed porous media columns
      of the type frequently used in geophysics, geochemistry and hydrology research.
      Positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive
      tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to
      trace flow through a 5 cm diameter * 20 cm tall sand packed column with and
      without an impermeable obstacle. In addition, a custom-made rotating column setup
      placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer
      propagation in a through-flowing column (10 cm diameter * 30 cm tall) packed with
      recovered aquifer sediments. A computational fluid dynamics software package
      FLUENT is used to model the observed flow dynamics. Tracer distributions obtained
      in the simulations in the smaller column uniformly packed with sand and in the
      column with an obstacle are remarkably similar to the reconstructed images in the
      PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for
      the larger column slurry-packed with sub-surface sediment and slow upward flow.
      In the numerical simulation of the SPECT study, two symmetric channels with
      increased permeability are prescribed along the column walls, which result in the
      emergence of two well-defined preferential flow paths. Methods and results of
      this work provide new opportunities in hydrologic and biogeochemical research.
      The primary target application for developed technologies is non-destructive, non
      perturbing, quantitative imaging of flow dynamics within laboratory scale porous
      media systems.

PMID- 24917695
TI  - Towards improving the care of children with pulmonary hypertension: The rationale
      for developing a Pediatric Pulmonary Hypertension Network.
AB  - Pulmonary hypertension (PH) and related pulmonary vascular diseases contribute to
      high morbidity and mortality and treatment options remain limited. Despite the
      availability of new drug therapies, the long-term outcomes of patients with
      severe PH remain poor. This may be especially true for many children with PH.
      Although most clinical studies have emphasized studies of adult patients, PH in
      pediatrics can be devastating and often contributes to poor outcomes in diverse
      clinical settings in newborns, infants and children. Unfortunately, studies that
      address the safety and efficacy of PH therapies in children are rare, as most
      pharmaceutical studies have focused on the adult population and only in patients
      with a fairly limited range of associated conditions. Thus, pediatric PH has been
      understudied and little is understood regarding the natural history, mechanisms
      of disease, and treatment of childhood PH. Limitations regarding current
      translational approaches to children with PH are partly due to the relatively
      small numbers of patients with PH associated with specific pediatric disorders at
      each center; the small number of well-established, multidisciplinary programs in
      pediatric PH; little communication between translational and clinician
      scientists; and limited interactions between existing PH programs. There is
      clearly a need to develop clinical infrastructure to better define the natural
      history and course of pediatric PH, to develop new strategies to identify at-risk
      patients early in their course, and to establish novel approaches to diagnose,
      monitor disease progression and treat children with PH. This article discusses
      the rationale, goals and initial steps in the establishment of an interactive
      network of investigators, care providers and multidisciplinary teams from several
      pediatric PH centers.

PMID- 24917696
TI  - Chemotherapy near the end of life: a retrospective single-centre analysis of
      patients' charts.
AB  - BACKGROUND: Chemotherapy near the end of life is an issue frequently discussed
      nowadays. The concern is that chemotherapy could cause more harm than good in a
      palliative situation; this is even truer as the patient nears death. The
      objective of our study is to evaluate the aggressiveness of patient care near the
      end of life by determining how many cancer patients receive chemotherapy during
      their final weeks. METHODS: In a retrospective analysis of patient charts, we
      investigated whether cancer patients had been treated with chemotherapy during
      the last four or two weeks of life. If they had, we looked at whether treatment
      was ongoing or newly initiated. RESULTS: Out of the 119 cancer patients who died
      in our hospital over two years, 14 (11.7%) received chemotherapy during the last
      four weeks of life, nine of whom (7.6%) in the last two weeks of life. Treatment
      had been ongoing in six (5%) and newly initiated for eight (6.7%) within four
      weeks of death. Corresponding figures for the last two weeks of life were seven
      patients (5.9%) who continued previously prescribed treatment and two (1.7%) who
      were started on chemotherapy. Patients given chemotherapy during the last four
      weeks of life were significantly younger than those who were not (p = 0.003).
      CONCLUSIONS: Cancer patient care in our hospital is not considered overly
      aggressive as only 7.6% of these patients receive chemotherapy within the last
      two weeks of life. To determine how aggressive care near the end of life really
      is, however, we suggest evaluating newly started chemotherapy alongside ongoing
      treatment. As the line between the effects (beneficience) and side effects
      (nonmaleficience) of chemotherapy is often very narrow, doctors and patients have
      to work together to find the best way of treading this fine line.

PMID- 24917697
TI  - miR-639 promotes the proliferation and invasion of breast cancer cell in vitro.
AB  - Breast cancer is characterised by an elevated capacity for tumour invasion and
      lymph node metastasis, but the cause remains to be determined. Recent studies
      suggest that microRNAs can regulate the evolution of malignant behaviours by
      regulating multiple target genes. In this study, we have first confirmed that miR
      639 is up-regulated in metastatic breast cancer tissues and cell line with highly
      invasive capacity. Furthermore, we provided evidence to demonstrate that up
      regulation of miR-639 contributes breast cancer invasion and metastasis. These
      data reveal a key role of miR-639 in breast cancer metastasis and support
      biological and clinical links between miR-639 and breast cancer. 

PMID- 24917699
TI  - Size-controllable synthesis and bandgap modulation of single-layered RF-sputtered
      bismuth nanoparticles.
AB  - We here report a simple and efficient method to grow single-layer bismuth
      nanoparticles (BiNPs) with various sizes on glass substrates. Optimal conditions
      were found to be 200 degrees C and 0.12 W/cm(2) at a growth rate of 6 A/s, with
      the deposition time around 40 s. Scanning electron microscope (SEM) images were
      used to calculate the particle size distribution statistics, and high-resolution
      X-ray diffraction (XRD) patterns were used to examine the chemical interactions
      between BiNPs and the substrates. By measuring the transmission spectra within
      the range of 300 to 1,000 nm, we found that the optical bandgap can be modulated
      from 0.45 to 2.63 eV by controlling the size of these BiNPs. These interesting
      discoveries offer an insight to explore the dynamic nature of nanoparticles. 

PMID- 24917700
TI  - Topographical control of cell-cell interaction in C6 glioma by nanodot arrays.
AB  - Nanotopography modulates the physiological behavior of cells and cell-cell
      interactions, but the manner of communication remains unclear. Cell networking
      (syncytium) of astroglia provides the optimal microenvironment for communication
      of the nervous system. C6 glioma cells were seeded on nanodot arrays with dot
      diameters ranging from 10 to 200 nm. Cell viability, morphology, cytoskeleton,
      and adhesion showed optimal cell growth on 50-nm nanodots if sufficient
      incubation was allowed. In particular, the astrocytic syncytium level maximized
      at 50 nm. The gap junction protein Cx43 showed size-dependent and time-dependent
      transport from the nucleus to the cell membrane. The transport efficiency was
      greatly enhanced by incubation on 50-nm nanodots. In summary, nanotopography is
      capable of modulating cell behavior and influencing the cell-cell interactions of
      astrocytes. By fine-tuning the nanoenvironment, it may be possible to regulate
      cell-cell communications and optimize the biocompatibility of neural implants. 

PMID- 24917701
TI  - Ammonia gas sensors based on chemically reduced graphene oxide sheets self
      assembled on Au electrodes.
AB  - We present a useful ammonia gas sensor based on chemically reduced graphene oxide
      (rGO) sheets by self-assembly technique to create conductive networks between
      parallel Au electrodes. Negative graphene oxide (GO) sheets with large sizes (>10
      MUm) can be easily electrostatically attracted onto positive Au electrodes
      modified with cysteamine hydrochloride in aqueous solution. The assembled GO
      sheets on Au electrodes can be directly reduced into rGO sheets by hydrazine or
      pyrrole vapor and consequently provide the sensing devices based on self
      assembled rGO sheets. Preliminary results, which have been presented on the
      detection of ammonia (NH3) gas using this facile and scalable fabrication method
      for practical devices, suggest that pyrrole-vapor-reduced rGO exhibits much
      better (more than 2.7 times with the concentration of NH3 at 50 ppm) response to
      NH3 than that of rGO reduced from hydrazine vapor. Furthermore, this novel gas
      sensor based on rGO reduced from pyrrole shows excellent responsive repeatability
      to NH3. Overall, the facile electrostatic self-assembly technique in aqueous
      solution facilitates device fabrication, the resultant self-assembled rGO-based
      sensing devices, with miniature, low-cost portable characteristics and
      outstanding sensing performances, which can ensure potential application in gas
      sensing fields. 

PMID- 24917702
TI  - The floppy iris syndrome - what urologists and ophthalmologists need to know.
AB  - INTRODUCTION: Benign prostatic hyperplasia (BPH) and cataract formation are
      common in older people. Medical management of symptomatic BPH is often preferred
      to surgical treatment as surgery increases the risk of morbidities, whereas,
      surgery is the main form of treatment to restore sight in patient with cataract.
      The clinical treatment of BPH is either alpha-1 adrenergic antagonist alone or
      combination of alpha reductase inhibitor and alpha adrenergic receptor (AR)
      antagonist. There are four alpha-AR antagonists currently available to treat BPH.
      The uroselective alpha-blocker tamsulosin is the most commonly used drug among
      all. Studies showed that the majority of the patients who develop intraoperative
      floppy iris syndrome (IFIS) were on tamsulosin. Women are more likely to develop
      cataract than men and some recent studies showed that tamsulosin is effective in
      treating female lower urinary tract symptoms and thereby can cause IFIS during
      cataract surgery. EVIDENCE ACQUISITION: We performed a critical review of the
      published articles and abstracts on association of IFIS with alpha-blockers and
      other medications as well as other medical conditions. EVIDENCE SYNTHESIS:
      Tamsulosin is the most common cause of formation of IFIS. However, not all
      patients given tamsulosin develop IFIS and cases have been reported without any
      tamsulosin treatment. CONCLUSION: Tamsulosin is a recognized cause to impede
      mydriasis and lead to IFIS during cataract surgery. Urologist should collaborate
      with their ophthalmology colleagues and general practitioner during prescribing
      tamsulosin in patients with history of cataract or waiting for planned cataract
      surgery. The increasing life expectancy and growth of older people will increase
      the number of men and women who suffer from lower urinary tract symptoms as well
      as cataract. Therefore, further research and studies are required to properly
      understand the relation of alpha blockers and IFIS.

PMID- 24917703
TI  - Single-incision laparoscopic surgery in urology.
AB  - INTRODUCTION: To assess the feasibility of single-incision laparoscopic surgery
      (SILS) in some urological surgeries. MATERIAL AND METHODS: This prospective study
      was conducted on 40 patients (27 males and 13 females) from January 2010 to June
      2011. Six procedures were done, SILS renal cyst decortication (n = 10), SILS
      varicocelectomy (n = 10), SILS orchiopexy (n = 10), SILS nephrectomy (n = 3),
      SILS pyelolithtomy (n = 6) and SILS adrenalectomy (n = 1). RESULTS: Postoperative
      complications included ileus (10%) and fever (10%) in SILS renal cyst ablation.
      SILS varicocelectomy had postoperative sequalae as persistent varicocele (10%)
      and hydrocele (10%). SILS orchiopexy was also done with a success rate 100% in
      this series. SILS pyelolithotomy was successfully done in 5 out of 6 patients and
      only 1 patient was converted to conventional laparoscopy. In SILS nephrectomy 1
      patient out of 3 was converted to conventional laparoscopy. CONCLUSION: SILS in
      urology has proven to be safe and feasible in the hands of experienced
      laparoscopic surgeons, using specially designed ports and instruments in selected
      patients.

PMID- 24917704
TI  - Demographics of Men Receiving Vasectomies in the US Military 2000-2009.
AB  - BACKGROUND: We hypothesize that there is a higher incidence of vasectomy within
      the military at a younger age based on this equal access health care system.
      MATERIALS AND METHODS: A review of the CHAMPS military database was conducted for
      men receiving vasectomies from 2000 to 2009. Age at vasectomy, number of
      children, race, religion, and marital status were recorded and incidence was
      computed. RESULTS: Total of 82,945 vasectomies was performed. The overall
      incidence to have a vasectomy was approximately 7.10 per 1000 men. The highest
      rate of occurrence was 14.4 per 1000 men in men 30-34 years old. Whites had a
      higher rate than blacks at 10.03 per 1000 men compared to 6.27 per 1000 men.
      Protestants had the highest rate at 8.44 per 1000 men, and Jewish people had the
      lowest at 1.86 per 1000 men. Married men had a rate of 12.3 per 1000 men, whereas
      single men were 1.03 per 1000 men. CONCLUSIONS: The incidence to have a vasectomy
      in the military was 7.10 per 1000 men, with an age adjusted rate at 8.66 per 1000
      men. This information may assist primary care providers in discussing vasectomies
      as a permanent form of contraception.

PMID- 24917705
TI  - An Advanced but Traditional Technique of Transurethral Resection of the Prostate
      in Order not to Overlook Stage T1 Prostate Cancer.
AB  - INTRODUCTION: A little deeper resection was done during transurethral resection
      of the prostate (TURP) for benign prostate hyperplasia (BPH) to fill the
      disparities of reported prevalence rates between latent and incidental prostate
      cancer, as well as in order not to overlook clinically significant incidental
      cancer. PATIENTS AND METHODS: We performed TURP in 995 patients who were
      diagnosed to have BPH. With a routine TUR setup, first most of the transition and
      central zones were resected. Then a slightly deeper resection of the residual
      adenoma and the peripheral zone than in the usual TURP was made. Pathological
      specimens were collected from 6 different parts. RESULTS: Incidental cancer was
      diagnosed in 226 patients (22.7%). Gleason scores were distributed as follows: 6
      or less in 150 cases (66.4%), 7 in 68 cases (30.1%), and 8 in 8 cases (3.5%).
      Even in the patients with lower prostate specific antigen (PSA), patients with
      incidental cancer and Gleason scores of 7 or more were 142 (21.2%) and 41 (28.9%)
      respectively at 0 < PSA < 4.0 ng/ml, and 95 (18.7%) and 26 (27.4%) respectively
      at 0 < PSA < 2.5 ng/ml. Multifocal/diffuse cancer was detected in 84 (37.2%)
      patients. CONCLUSIONS: With our method of advanced TURP, we detected incidental
      cancer at almost the same rate as reported in latent cancer. When TURP is
      performed, incidental cancer as well as to relieve voiding difficulties must not
      be overlooked, because there must be a considerable number of clinically
      significant incidental cancer of higher Gleason scores, and of multifocal/diffuse
      lesions.

PMID- 24917706
TI  - Significance of uracil/tegafur for preventing intravesical recurrence of non
      muscle invasive urothelial carcinoma of the bladder.
AB  - BACKGROUND: The objective of this study was to assess the role of uracil/tegafur
      (UFT) and its metabolite gamma-butyrolactone (GBL), a potent inhibitor of
      angiogenesis, in the prevention of intravesical recurrence in patients with non
      muscle invasive urothelial carcinoma of the bladder (NMIUCB). PATIENTS AND
      METHODS: This study included 48 patients with NMIUCB following complete
      transurethral resection who were randomly divided into 27 receiving UFT therapy
      (group A) and 21 without any adjuvant therapies (group B). Serum levels of GBL,
      vascular endothelial growth factor, basic fibroblast growth factor, platelet
      derived growth factor and interleukin-8 were measured. RESULTS: There was no
      significant difference in the intravesical recurrence-free survival between
      groups A and B. Despite the lack of significant differences in serum levels of
      vascular endothelial growth factor, basic fibroblast growth factor, platelet
      derived growth factor and interleukin-8, serum GBL in group A was significantly
      greater than in group B. Multivariate analysis identified tumor size as an
      independent predictor of intravesical recurrence irrespective of the other
      factors examined. CONCLUSIONS: Despite the significant induction of GBL, adjuvant
      UFT therapy failed to show a preventive effect on intravesical recurrence of
      NMIUCB. Therefore, we should consider enhancing the anti-angiogenic effect of GBL
      using an alternative administration schedule of UFT.

PMID- 24917707
TI  - Varicocelectomy to treat pain, and predictors of success: a prospective study.
AB  - OBJECTIVE: We attempted to examine the success rate of varicocele ligation when
      performed for the treatment of pain and to evaluate all the predictor factors
      that may affect the resolution of pain. PATIENTS AND METHODS: From January 2008
      to January 2011, a total 152 patients presented with painful varicocele to our
      out-patient clinic. While waiting for surgery, 7 patients (4.6%) resolved their
      pain with conservative management and 145 patients underwent varicocelectomy due
      to failure. The first follow-up visit was after 1 week to check the wounds and
      130 patients attended the second visit after 3 months. Follow-up evaluation
      included physical examination, questioning of pain severity (compared with
      preoperative pain severity), development of any postoperative complications, and
      color Doppler to study recurrence reflux. RESULTS: During the study period,
      145/397 (36.5%) patients underwent varicocelectomy for pain. Of the 145 men
      operated on for pain 130 (89.6%) were available for follow-up. A subinguinal
      approach was used in 93 patients (71.5%) and high ligation in 37(28.5%). Of the
      130 patients contacted after surgery, 109 (83.8%) reported complete resolution of
      pain, 7 (5.4%) had partial resolution of pain and 14 did not show benefit from
      surgery. There was no association between varicocele grade, quality of pain, type
      of varicocele ligation, or recurrence and pain resolution after surgery, only the
      duration of pain seems to be a factor that is considerably associated with pain
      resolution. CONCLUSION: Varicocelectomy is a successful option for treatment of
      painful varicocele in selected patients. The duration of pain may predict
      outcomes in these patients.

PMID- 24917708
TI  - Presentation and treatment of subfertile men with balanced translocations: the
      cleveland clinic experience.
AB  - INTRODUCTION: Balanced chromosomal translocations are a relatively common (2-7%)
      finding among infertile couples. We report clinical features of males with
      translocations at our institution. MATERIALS AND METHODS: Data was collected on
      men presenting for infertility evaluation between July 2006 March 2010, including
      presentation, medical history, and infertility treatments. Criteria for genetic
      evaluation, consisting of karyotype and Y-linked microdeletion assay, included
      severe oligozoospermia or azoospermia (sperm concentration < 2.5*106/ml) or a
      history of recurrent miscarriages. RESULTS: Of the 4,612 patients in our male
      infertility clinic 306 met criteria for genetic evaluation. Three patients had a
      balanced translocation, of which 2 had Robertsonian translocations, and 1 had a
      balanced translocation. One patient had normal bulk semen parameters, normal
      volume azoospermia, and oligoasthenoteratozoospermia. All patients were offered
      medical genetics consultation. Potential pregnancy outcomes were evaluated using
      a predictive software package. One patient had intratubular germ cell neoplasia
      and underwent orchiectomy; subsequent fertility evaluation has been deferred. The
      other 2 are considering in-vitro fertilization with pre-implantation genetic
      evaluation. CONCLUSIONS: Given the low incidence of balanced translocations
      detected in our population, better clinical indicators other than semen
      parameters or history of recurrent pregnancy loss are needed to determine
      screening for this finding.

PMID- 24917709
TI  - Complete chemotherapeutic regression of a non-metastatic case of primary pure
      small cell carcinoma of the prostate.
AB  - Pure small cell carcinoma of the prostate (SCPCa) is a very rare condition
      usually with poor survival after diagnosis. It seems to show different clinical
      features compared to other prostate cancer subtypes, specifically adenocarcinoma.
      Here, we present a 74-year-old man early diagnosed with SCPCa treated with a
      cisplatine and etoposide regimen. There was no metastasis found in imaging
      studies and bone scan. The patient mostly complained of obstructive symptoms
      which were relieved after resection. Interestingly, our patient experienced a
      disease free condition after chemotherapy and no further progression was found.
      This could implicate the critical role of early diagnosis in the treatment of
      SCPCa despite its aggressive nature. 

PMID- 24917710
TI  - Conservative treatment of malignant fibrous histiocytoma of the kidney: a case
      report.
AB  - Primary renal malignant fibrous histiocytoma is an extremely rare disease. There
      are neither clinical nor radiological signs to distinguish it from the most
      common renal cell carcinoma. Its prognosis is poor because of its tendency to
      locally recur and metastasize. Therefore, early diagnosis and proper treatment
      are very important. We present the case of a 66-year-old woman diagnosed with
      primary renal malignant fibrous histiocytoma who underwent partial nephrectomy.
      After 41 months' follow-up, there was no evidence of any recurrence. To our
      knowledge, this is the first reported case of conservative surgery for this kind
      of tumor. 

PMID- 24917712
TI  - Bladder Outlet Obstruction Secondary to a Brunn's Cyst.
AB  - INTRODUCTION: Bladder outlet obstruction in younger men is often secondary to
      urethral stricture disease. In the older population it is often a result of
      benign prostatic hypertrophy. MATERIALS AND METHODS: We describe the diagnosis,
      treatment, and outcome of a rare case of a Brunn's cyst causing bladder outlet
      obstruction in a 43-year-old male who was evaluated for obstructive urinary
      complaints. RESULTS: Ultrasound and cystoscopy revealed a cystic lesion at the
      bladder neck. Transurethral unroofing of the cyst resulted in resolution of the
      obstructive symptoms and resumption of normal voiding. Final pathology revealed a
      cystic structure with predominately denuded urothelium with multiple submucosal
      cystically dilated von Brunn's nests, most consistent with a Brunn's cyst. A
      search of the literate reveals only one similar case. CONCLUSIONS: We present the
      rare case of a Brunn's cyst causing bladder outlet obstruction in a young man.

PMID- 24917713
TI  - Metastatic malignant melanoma to the bladder: a case series.
AB  - BACKGROUND: Metastatic melanoma to the bladder is rarely reported, and the role
      of surgery is still largely unknown. We review 4 such cases and highlight their
      management and outcomes. We also review the relevant literature. METHODS: The
      Mayo Clinic tumor database was searched and 4 such cases were found. RESULTS: All
      4 patients were treated locally with transurethral resection. The only patient
      who had a solitary metastasis did relatively well, having no evidence of disease
      10 months after his presentation, while the other 3 died within 6 months. The
      literature highlights various approaches to management, but there is no
      definitive evidence that radical cystectomy offers any benefit over transurethral
      resection. CONCLUSION: Resection may improve survival in the setting of a
      solitary metastasis, but there is no evidence that radical cystectomy offers any
      benefit over local resection. With diffuse disease, however, resection is likely
      only beneficial for treatment of hematuria.

PMID- 24917714
TI  - The acute pediatric scrotum: presentation, differential diagnosis and management.
AB  - Both pediatric and adult urologists frequently evaluate pediatric patients with
      an acute scrotum. We present a detailed review on the acute pediatric scrotum
      highlighting the clinical presentation, differential diagnosis and management of
      this common clinical condition. It is important to highlight that a testicular
      torsion is the most important differential diagnosis and the main priority in
      each case is to diagnosis and treat a potential testicular torsion is of the
      essence. The aim of our extensive review is to update/review the appropriate
      evaluation and management of the acute scrotum and to guide the clinician in
      distinguishing testicular torsion from the other conditions that commonly mimic
      this surgical emergency. This review is useful for trainees in UK and Europe who
      plan to take the FRCS (Urol) examination. 

PMID- 24917715
TI  - Expression of Angiotensin II Type 1 Receptor in Rat Bladder Smooth Muscle Cells
      in Response to a Streptzotocin Induced Diabetes Mellitus Model.
AB  - INTRODUCTION: The aim of this study was to investigate angiotensin II type 1
      (AT1) receptors in rat bladder smooth muscle cells and alterations of AT1
      receptors by diabetes mellitus and diuretic states. MATERIALS AND METHODS:
      Diabetes and diuresis were induced in adult female rats by a single
      intraperitoneal injection of streptozotocin and feeding 5% sucrose in water.
      Cystometry was performed on control, diuretic, and diabetic rats at 2 and 8 weeks
      after treatment. Immunohistochemical staining was used to detect expression of
      AT1 receptors in the bladder smooth muscle cell membrane. RESULTS AND
      CONCLUSIONS: In diabetic rats, expression of AT1 receptors in the bladder smooth
      muscle cell membrane increased at 2 weeks and further increased at 8 weeks. The
      local renin-angiotensin system in the rat bladder might be activated by the
      continuous hyperglycemia caused by intraperitoneal injection of streptozotocin
      administration.

PMID- 24917716
TI  - Vascularized Dartos Flap in Conjunction with Tubularized Incised Plate
      Urethroplasty: Single versus Double Flaps for Management of Distal Hypospadias.
AB  - OBJECTIVE: To compare the results of Snodgrass repair with single versus double
      vascularized dartos pedicle flap for neouretheral coverage. PATIENTS AND METHODS:
      Fifty-eight pediatric patients with mean age 41.5 +/- 21 months (range 9-96
      months) underwent primary hypospadias repair, 39 uncircumcised and 19
      circumcised, classified into 2 groups according to coverage of the neourethra.
      Single layer coverage (Group I) was performed in 28 (48.3%) while double layers
      coverage (Group II) was done in 30 (51.7%) cases. RESULTS: After mean follow-up
      8.6 +/- 5.4 months (range 3-24 months), good cosmetic results with vertical slit
      like meatus at the tip of conical shaped glans were obtained in 53 cases (91.4%).
      Totally 5 cases occurred postoperative complications, of which 4 cases in Group I
      [2 (7.1%) with urethrocutaneous fistula, 1 (3.6%) with meatal stenosis and 1
      (3.6%) with skin necrosis], 1 case in Group II [glanular dehiscence (3.3%)]. No
      fistula was observed in Group II. CONCLUSION: The Snodgrass tubularized incised
      plate repair in conjunction with double layer coverage of the neourethra could be
      considered the procedure of choice for distal hypospadias with low complications
      rate especially urethrocutaneous fistula.

PMID- 24917717
TI  - Place of non contrast thin-slice spiral computed tomography in evaluation of
      stone-free ratio after percutaneous nephrolithotomy.
AB  - PURPOSE: To search the place of non contrast abdominal computed tomography to
      detect the stone-free rate after percutaneous nephrolithotomy (PNL) and the
      clinical importance of its superiority against to plain film radiography (KUB).
      MATERIALS AND METHODS: Between February 2006 and July 2010, 62 patients including
      27 women had no stone detected peroperative fluoroscopy and nephroscopy during
      PNL were included. Patients whom stone was not detected under 5 mm section upper
      abdomen non contrast spiral CT and KUB control in postoperative day 3 were
      defined as Group 1; patients whom stone was detected in a single slice CT were
      defined as clinically insignificant fragment (CIF)(Group 2) and patients whom
      stone was detected at least in two slice were defined as rest fragment (Group 3).
      RESULTS: Median stone size were 22.3 mm (19-37 mm). Preoperative stone
      localization of groups were upper calyx, middle calyx, pelvis, lower calyx and
      2.1, 14.9, 25.5 and 57.4%, respectively. CIF was detected in postoperative CT
      control of 12 (25.5%) patients whom stone was not followed in KUB and rest
      fragment was detected in 6 (12.8%) patients. Three of patients whom rest fragment
      was detected required an additional intervention for stone. CONCLUSION: KUB which
      is routinely used to determine stone-free ratio after PNL operation is not
      sufficient to detect rest calculi and/or CIF existence in 38.3% patients. But
      when it is considered that most of rest stones detected were CIF and only 6.3%
      patients had additional intervention required rest calculi. We can think that CT
      follow-up is not absolutely required.

PMID- 24917718
TI  - Simultaneous Cystectomy and Nephroureterectomy due to Synchronous Upper Urinary
      Tract Tumors and Invasive Bladder Cancer: Open and Laparoscopic Approaches.
AB  - INTRODUCTION: It is not unusual for bladder tumors to appear following
      transitional cell carcinoma of the upper urinary tract (UUT), with involvement of
      the UUT, following invasive bladder cancer, being less common. The synchronous
      presence of transitional cell carcinoma of the bladder and of the UTT is
      exceptional. METHODS: Fifteen simultaneous cystectomies with nephroureterectomies
      were performed due to synchronous UUT and invasive bladder cancers (1997-2009).
      Surgery was performed using an open approach in 10 patients, while the last 5
      procedures were performed laparoscopically. RESULTS: The mean age was 68.7 years.
      Mean surgery time was 348.6 minutes. Mean blood loss was 816 ml. Acute renal
      failure was the most frequent postoperative complication being present in 5
      patients (33%). There was 1 case of a leak in the ureter-intestinal anastomosis
      (open approach), which required placement of a left-sided percutaneous
      nephrostomy. There were 2 cases of postoperative mortality, both in the open
      approach series and with intestinal neobladder. Mean follow-up time for the whole
      series was 21.25 months. Eight cases experienced metastatic progression of the
      disease (mean follow-up 17 months). CONCLUSION: Though multi-site studies with
      longer follow-up and a greater numbers of patients are needed, the moment at
      which urothelial tumors appear seems to influence their prognosis, with lower
      survival rates for tumors that synchronically appear.

PMID- 24917719
TI  - Temporary prostatic urethral stenting as a provocative tool to determine surgical
      eligibility in complex bladder outlet obstructed patients: our initial
      experience.
AB  - BACKGROUND/AIMS: To evaluate the usefulness of a temporary prostatic urethral
      stent to determine which complex surgical patients would benefit from definitive
      surgical management of their benign prostatic hyperplasia. METHODS: We
      retrospectively analyzed our benign prostatic hyperplasia database and identified
      all patients that received at least one temporary prostatic urethral stent
      between April 2008 and December 2010. RESULTS: Forty Spanner(TM) stents were
      placed in 20 patients. Mean age was 78.1 years and prostate size was 62.1 cm(3).
      Urinary retention was present in 60% (12/20) of patients. No statistically
      significant changes in mean maximal flow rate, average flow rate, and post void
      residual was noted. Seven patients (35%) did well with the stent and progressed
      to definitive surgical management whereas 10% of the cohort (2/20) leaked urine
      with the stent in place and subsequently went back to catheter management.
      Another 30% (6/20) were unable to tolerate the stent while 1 patient passed away
      unrelated to the stent. CONCLUSIONS: The use of the temporary prostatic urethral
      stent provided a good provocative test that enabled patients to experience what
      their voiding status would be if they were to undergo definitive surgical
      management.

PMID- 24917720
TI  - Pediatric and Adult Urological Publications: Trend over the Last 15 Years between
      1996 and 2010.
AB  - PURPOSE: The aim of this study was to determine the trends in urological
      publications from 1996 to 2010. METHODS: We retrieved as many urology-related
      articles as possible from Medline articles between 1 January 1996 and 31 December
      2010, and attempted to retrieve as many urology articles as possible from all
      Medline recorded journals (urology-specific and non-urology-specific journals
      indiscriminately), using the key words: "urology", "pediatric urology",
      "bladder", "kidney"and others. The search was limited to "all adults"(i.e. adult
      urology), "all children" (i.e. pediatric urology) as well as female and male
      urology. We repeated the search by using a certain limit each time according to
      the publication types as classified by Medline, and collected the total number of
      publications per year for the 15 years of the specified period. Regression
      analysis was used to determine the effect of the publication year upon the number
      of publications of each type. RESULTS: There was a steady increase over time in
      the number of total publications both in pediatric and adult urology, with a
      sharper rise in the number of meta-analysis publications. At the same time there
      was a decrease in the number of case reports over the last years. CONCLUSIONS:
      New medical information available to urology and pediatric urology specialists
      increases over time and thus increases.

PMID- 24917721
TI  - The clinical effectiveness of intravesical sodium hyaluronate (cystistat(r)) in
      patients with interstitial cystitis/painful bladder syndrome and recurrent
      urinary tract infections.
AB  - OBJECTIVE: Painful bladder syndrome/interstitial cystitis (PBS/IC) and recurrent
      urinary tract infections (UTI) are clinically challenging conditions to manage in
      patients. We evaluate the clinical use of intravesical sodium hyaluronate
      (Cystistat(r)) in both these patient groups who have completed treatment.
      PATIENTS AND METHODS: Thirteen patients with recurrent UTIs (Group I) and 8
      patients with PBS/IC (Group II) received intravesical sodium hyaluronate
      (Cystistat(r)). Preinstallation demographic parameters were statically comparable
      in both groups. The mean age of presentation was 54.6 years in Group I and 57.5
      years in Group II (p = 0.9). All 13 patients in Group I were on low dose
      antibiotics. The mean number of installations completed in both groups was 9
      (range 4-21). RESULTS: Data was collected prospectively using a standard pre- and
      post-treatment questioner with the pelvic pain and urinary/frequency patient
      symptom scale. At a mean follow-up of 21 months a significant improvement in
      bladder pain (p = 0.05), daytime frequency (p = 0.03) and quality of life (p =
      0.02) was noted in patients in Group I. Two patients had breakthrough UTIs during
      treatment. Within Group I, 7 (53%) patients responded well to treatment. Patients
      in Group II had a significant improvement in bladder pain (p = 0.02), urgency (p
      = 0.01), nocturia (p = 0.01) and quality of life (p = 0.04). Within Group II, 6
      patients (75%) responded to treatment. CONCLUSION: Intravesical sodium
      hyaluronate (Cystistat(r)) can be used with minimal side effects and good
      compliance in both groups of patients with PBS and recurrent UTIs. Longer follow
      up and larger patient numbers in both groups will be required to confirm the long
      term efficacy of these two clinically challenging groups of patients.

PMID- 24917722
TI  - Use of the Laparoscope Holder for Liver Retraction during Urological Laparoscopic
      Surgery.
AB  - PURPOSE: During laparoscopy, as in open surgery, exposure is critical. Here, we
      describe the use of a laparoscope holder to facilitate the liver lift during
      urological laparoscopic surgery. MATERIALS AND METHODS: Laparoscopic right
      radical nephrectomy (n = 3), partial nephrectomy (n = 1), and adrenalectomy (n =
      2) were performed with 4 ports. At the beginning of the operation, the small
      snake retractor was placed through the 5-mm port under direct vision and the
      liver was lifted in the appropriate direction to optimize exposure. RESULTS: The
      laparoscope holder provided quick, reproducible retraction to facilitate
      exposure. No complications occurred with its use. The device reduced the need for
      a dedicated second assistant to stand bedside. CONCLUSIONS: We achieved
      significant improvements in the safety and efficiency of liver retraction during
      urological laparoscopic surgery using the laparoscope holder.

PMID- 24917723
TI  - Ureteroscopy assisted retrograde nephrostomy for complete staghorn renal calculi.
AB  - Complete staghorn calculi are typically managed with percutaneous nephrolithotomy
      (PCNL). However, dilating nephrostomy and inserting a nephro access sheath can be
      difficult to perform without hydronephrosis. We reported the procedure of
      ureteroscopy-assisted retrograde nephrostomy (UARN) during PCNL. UARN is
      effective without dilating the renal collecting system in cases of complete
      staghorn calculi. A 63-year old female with a left complete staghorn renal
      calculus was referred to our hospital. Under general and epidural anesthesia, the
      patient was placed in a modified-Valdivia position. A flexible ureteroscope was
      inserted and a Lawson retrograde nephrostomy puncture wire was advanced into the
      flexible ureteroscope. The puncture wire was forwarded along the route from the
      renal pelvis to the exit skin. Calculus fragmentation was done using a pneumatic
      lithotripter and the Ho: YAG laser. UARN during PCNL was effective for the
      treatment of a complete staghorn calculus. 

PMID- 24917724
TI  - The progression of nephrogenic metaplasia of the urinary bladder to clear cell
      adenocarcinoma: a case report.
AB  - Nephrogenic metaplasia (or nephrogenic adenoma) and clear cell adenocarcinoma of
      the bladder are uncommon lesions that cause diagnostic dilemmas for pathologists
      due to their similar morphologic features. Nephrogenic metaplasia describes a
      lesion in the lower urinary tract that is composed of small tubules resembling
      renal medullary tubules. It has been suggested that nephrogenic metaplasia may
      progress to clear cell adenocarcinoma but this possibility is not widely
      accepted. We present a case of clear cell adenocarcinoma of the bladder arising
      from nephrogenic metaplasia and discuss the evidence behind the association of
      these two distinct rare lesions. 

PMID- 24917725
TI  - Delayed lower urinary tract symptoms and erectile dysfunction after acute episode
      of coccidioidal meningitis.
AB  - We present an interesting case of a 27-year-old male with coccidioidal meningitis
      who developed permanent erectile dysfunction (ED) and lower urinary tract
      symptoms 3 months after initiation of therapy. The patient presented to the
      urology clinic with a complaint of a weak stream, urinary urgency and frequency,
      as well as enuresis which were only moderately controlled with anti-cholinergics.
      His ED responded well to phosphodiesterase-5 inhibitors. After an extensive
      review of the literature, this is the first report of delayed presentation of ED
      and lower urinary tract symptoms secondary to coccidioidal meningitis. 

PMID- 24917726
TI  - Serum testosterone level and semen indices in sulfur mustard exposed men: comment
      on "sperm chromatin structure assay analysis of Iranian mustard gas casualties: a
      long-term outlook".

PMID- 24917727
TI  - Advances in male reproductive surgery: robotic-assisted vasovasostomy.
AB  - It is estimated that 3-6% of all vasectomised men request vasectomy reversal for
      different reasons. Microsurgical vasovasostomy is the gold standard technique of
      vasectomy reversal. However, the microsurgical technique is time-consuming and
      challenging to most urological surgeons. Therefore, alternative methods of vasal
      anastomosis have been studied including robotic-assisted vasovasostomy. This
      review discusses the feasibility and practice of robotic-assisted vasovasostomy.
      Based on the available studies robotic-assisted vasovasostomy is feasible. The
      reported rate of vasal patency associated with this new technique is similar to
      that of microsurgical vasovasostomy. There is no clear difference between the 2
      approaches in terms of operating time. Robotic-assisted vasovasostomy does not
      appear to afford significant advantages in the era of vasectomy reversal. 

PMID- 24917729
TI  - Non-invasive evaluation of bladder outlet obstruction in men suspected of benign
      prostatic hyperplasia: usefulness of the d index.
AB  - OBJECTIVE: To compare a new index of voiding dysfunction (D) based purely on free
      uroflow vs. Abrams-Griffiths (A-G) number obtained from intubated flow, for
      classification of bladder outlet obstruction in men. PATIENTS AND METHODS:
      Urodynamic tracings of 60 non-neurological patients (30 before transurethral
      resection of the prostate and of 30 men suspected of benign prostatic hyperplasia
      included in a medical therapy trial) were retrospectively analyzed. The Valentini
      Besson-Nelson model was used to evaluate the value of the D index. A-G was
      obtained from intubated flows. Obstruction was defined as D > 32.5 cm H2O
      (translation of A-G criterion). RESULTS: D showed 82.05% sensitivity with 66.66%
      specificity; the positive predictive value was 82.05% and the negative predictive
      value 66.66% for the whole population, 83.3 vs. 80.9% sensitivity with 58.3 vs.
      77.7% specificity for pre- transurethral resection of the prostate vs. medical
      therapy group. CONCLUSION: D index which can be obtained from a free uroflow
      appears as a valuable alternative to invasive urodynamic investigations when the
      diagnosis of bladder outlet obstruction needs to be more solidly established
      before a treatment decision or in men suspected of benign prostatic hyperplasia
      who elect for watchful waiting.

PMID- 24917728
TI  - Comparison of the loss of renal function after cold ischemia open partial
      nephrectomy, warm ischemia laparoscopic partial nephrectomy and laparoscopic
      partial nephrectomy using microwave coagulation.
AB  - PURPOSE: Nephron sparing surgery is an effective surgical option in patients with
      renal cell carcinoma. Laparoscopic partial nephrectomy involves clamping and
      unclamping techniques of the renal vasculature. This study compared the
      postoperative renal function of partial nephrectomy using an estimation of the
      glomerular filtration rate (eGFR) for a Japanese population in 3 procedures; open
      partial nephrectomy in cold ischemia (OPN), laparoscopic partial nephrectomy in
      warm ischemia (LPN), and microwave coagulation using laparoscopic partial
      nephrectomy without ischemia (MLPN). MATERIALS AND METHODS: A total of 57
      patients underwent partial nephrectomy in Yokohama City University Hospital from
      July 2002 to July 2008. 18 of these patients underwent OPN, 17 patients received
      MLPN, and 22 patients had LPN. The renal function evaluation included eGFR, as
      recommended by The Japanese Society of Nephrology. RESULTS: There was no
      significant difference between the 3 groups in the reduction of eGFR. eGFR loss
      in the OPN group was significantly higher in patients that experienced over 20
      minutes of ischemia time. eGFR loss in LPN group was significantly higher in
      patients that experienced over 30 minutes of ischemia time. CONCLUSION: This
      study showed that all 3 procedures for small renal tumor resection were safe and
      effective for preserving postoperative renal function.

PMID- 24917730
TI  - Prognostic Factors Influencing Postoperative Development of Chronic Kidney
      Disease in Patients with Small Renal Tumors who Underwent Partial Nephrectomy.
AB  - BACKGROUND: The objective of this study was to determine factors associated with
      the postoperative development of chronic kidney disease (CKD) following partial
      nephrectomy. PATIENTS AND METHODS: This study included 109 patients with normal
      renal function treated with partial nephrectomy for small renal tumors. Of these,
      73 and 36 patients underwent open partial nephrectomy (OPN) and laparoscopic
      partial nephrectomy (LPN), respectively. RESULTS: Among several parameters, there
      was a significant difference only in the ischemia time between the OPN and LPN
      groups. During the median observation period of 53.4 months, CKD, defined as
      estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m(2),
      developed in 29 (39.7%) and 14 (38.9%) patients in the OPN and LPN groups,
      respectively. Univariate analysis identified age at surgery, diabetes and
      preoperative eGFR as significant predictors of the postoperative development of
      CKD; however, only age at surgery and preoperative eGFR appeared to be
      independently related to CKD-free survival. In fact, there was a significant
      difference in the CKD-free survival between patients without any independent risk
      factor and those with at least one of these independent risk factors.
      CONCLUSIONS: Careful management following partial nephrectomy is necessary for
      elderly patients and/or those with impaired renal function, even mild, before
      surgery.

PMID- 24917731
TI  - The effect of microsurgical varicocelectomy on semen parameters in men with non
      obstructive azoospermia.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of microsurgical
      subinguinal varicocelectomy on semen parameters in azoospermic men with clinical
      varicocele and to determine the predictive parameters of postoperative
      improvement. METHODS: Twenty-three men with non-obstructive complete azoospermia
      and varicocele underwent subinguinal open microsurgical varicocele repair. The
      outcome was assessed in terms of improvement in semen parameters after surgical
      repair for varicocelectomy. RESULTS: Bilateral varicocelectomy was performed on
      15 patients and unilateral (left) varicocelectomy was performed on 8 patients. In
      the post-operative period, of the 23 patients, 7 (30.4%) had motile sperm in the
      ejaculate. The mean sperm concentration of these patients was 1.34 +/- 2.6 *
      10(6)/ml and the mean total sperm motility was 37.5 +/- 15.5%. CONCLUSION:
      Infertile men with non-obstructive azospermia can have improvement in semen
      analysis after subinguinal microsurgical repair of varicoceles. Motile sperm in
      ejaculate were detected after microsurgical varicocele repair.

PMID- 24917732
TI  - Nomogram to predict prostate cancer diagnosis on primary transrectal ultrasound
      guided prostate biopsy in a contemporary series.
AB  - OBJECTIVE: Transrectal ultrasound-guided biopsy (TRUSB) remains the mainstay for
      prostate cancer (CaP) diagnosis. Numerous variables have shown associations with
      development of CaP. We present a nomogram that predicts the probability of
      detecting CaP on TRUSB. METHODS: After obtaining institutional review board
      approval, all patients undergoing primary TRUSB for CaP detection at a single
      center at our institution between 2/2000 and 9/2007 were reviewed. Patients
      undergoing repeat biopsies were excluded, and only the first biopsy was included
      in the analysis. Variables included age at biopsy, race, clinical stage, prostate
      specific antigen (PSA), number of cores removed, TRUS prostate volume (TRUSPV),
      body mass index, family history of CaP, and pathology results. S-PLUS 2000
      statistical software was utilized with p < 0.05 considered significant. Cox
      proportional hazards regression models with restricted cubic splines were
      utilized to construct the nomogram. Validation utilized bootstrapping, and the
      concordance index was calculated based on these predictions. RESULTS: A total of
      1,542 consecutive patients underwent primary TRUSB with a median age of 64.2
      years (range 34.9-89.2 years), PSA of 5.7 ng/ml (range 0.3-3,900 ng/ml), number
      of cores removed of 8.0 (range 1- 22) and TRUSPV of 36.4 cm(3) (range 9.6-212.0
      cm(3)). CaP was diagnosed in 561 (36.4%) patients. A nomogram was constructed
      incorporating age at biopsy, race, PSA, body mass index, clinical stage, TRUSPV,
      number of cores removed, and family history of CaP. The concordance index when
      validated internally was 0.802. CONCLUSIONS: We have developed and internally
      validated a model predicting cancer detection in men undergoing TRUSB in a
      contemporary series. This model may assist clinicians in risk-stratifying
      potential candidates for TRUSB, potentially avoiding unnecessary or low
      probability TRUSB.

PMID- 24917733
TI  - Hematuria secondary to benign prostatic hyperplasia: retrospective analysis of
      166 men identified in a single one stop hematuria clinic.
AB  - INTRODUCTION: Hematuria secondary to benign prostatic hyperplasia (BPH) can occur
      due to a vascular primary gland itself or due to the vascular re-growth of the
      prostate following a transurethral resection of the prostate (TURP). We aim to
      evaluate the clinical presentation and management in patients within both these
      groups. MATERIALS AND METHODS: We retrospectively archived the data of 166 men
      diagnosed with hematuria secondary to BPH from our hematuria clinic database from
      March 2003 and March 2006. The 166 patients were divided into 2 groups: Group I
      (n = 94) hematuria with no previous TURP; Group II (n = 72) hematuria with
      previous TURP. The clinical management in both groups included reassurance,
      commencement of a 5-alpha reductase inhibitor (finasteride) or a primary TURP in
      Group I or re-do TURP in Group II. RESULTS: The median age was 73 years (range 45
      94 years) for both groups. Outcomes combined for both groups included:
      reassurance alone in 26% (n = 43), finasteride in 51% (n = 84) and TURP in 12% (n
      = 19). Patients managed with reassurance alone or TURP had no further episodes of
      hematuria. At a mean follow-up was 18 months (range 7-22 months), 2 patients
      treated with finasteride re-bled but did require further intervention. A further
      2 men elected to stop finasteride due to erectile dysfunction and gynecomastia
      respectively. CONCLUSION: BPH can present with hematuria. Following re-evaluation
      in a hematuria clinic, the lack of any subsequent cancer diagnosis in these
      patients suggests that repeat hematuria investigations should be carefully re
      considered.

PMID- 24917734
TI  - A retrospective review of factors associated with vasovasostomies in United
      States military members.
AB  - BACKGROUND: Men seeking a vasectomy should receive counseling prior to the
      procedure that includes discussion of later seeking a reversal. We sought to
      determine demographic factors that may predispose patients to possibly later seek
      a vasectomy reversal. METHODS: All U.S. Military electronic health records were
      searched between 2000 and 2009 for either a vasectomy or vasovasostomy procedure
      code. Aggregate demographic information was collected and statistical analysis
      performed. RESULT: A total of 82,945 patients had a vasectomy of which 4,485 had
      a vasovasostomy resulting in a vasovasostomy-to-vasectomy rate of 5.04%. The
      average age at vasovasostomy was 34.9+/-5.0, with an average interval of 4.1+/
      2.2 years. Men undergoing a vasectomy at a younger age were more likely to have a
      vasovasostomy. Various religions did have statistically significant differences.
      Within ethnic groups, only Native Americans [OR=1.39 (95% CI 1.198-1.614)] and
      Asians [OR=0.501 (95% CI 0.364-0.690)] had statistically significant differences
      when compared to Caucasians. Men with more children at the time of vasectomy were
      more likely to have a vasovasostomy. CONCLUSION: Younger men, Native Americans,
      and men with more children at vasectomy were more likely to undergo a
      vasovasostomy. The reason for these differences is unknown, but this information
      may assist during pre-vasectomy counseling.

PMID- 24917735
TI  - Significance of ureteroscopic biopsy grade in patients with upper tract
      urothelial carcinoma.
AB  - BACKGROUND: The objective of this study was to assess the significance of the
      ureteroscopic biopsy grade for patients with upper tract urothelial carcinoma
      (UTUC). PATIENTS AND METHODS: This study included 40 patients who were diagnosed
      with a single focus of UTUC by ureteroscopic biopsy and subsequently underwent
      nephroureterectomy. The significance of the biopsy grade as a predictive factor
      for pathological outcomes of nephroureterectomy was retrospectively analyzed.
      RESULTS: Of these 40 patients, 19 (47.5%) and 21 (52.5%) were diagnosed with low
      and high grade UTUC, respectively. The ureteroscopic biopsy grade matched the
      pathological grade of surgically resected specimens in 35 of the 40 cases
      (87.5%), and there was a significant correlation between the biopsy and
      pathological grades (p < 0.001). Furthermore, the biopsy grade was also shown to
      be closely associated with the pathological stage (p < 0.001); that is, only 1 of
      the 19 patients (5.3%) with biopsy low grade UTUC were pathologically diagnosed
      as having muscle invasive disease, while 17 of the 21 patients (81.0%) with
      biopsy high grade UTUC appeared to show tumor invasion into muscle or deeper.
      CONCLUSIONS: The grade of UTUC on ureteroscopic biopsy could provide accurate
      diagnostic information on the final pathology of nephroureterectomy specimens.

PMID- 24917736
TI  - Thiotepa versus Bacille Calmette-Guerin in Non-Muscle Invasive Bladder Cancer.
AB  - OBJECTIVE: The efficacy of intravesical thiotepa was evaluated compared with
      administration of Bacille Calmette-Guerin (BCG) in non-muscle invasive bladder
      cancer. PATIENTS: In this multicenter, prospective, randomized study, eligible
      patients were those with proven non-muscle invasive bladder cancer. All patients
      were randomly allocated to Group A, receiving intravesical thiotepa (at a dose of
      30 mg/30 ml) once weekly for 9 consecutive weeks and then monthly for 12 months
      or Group B, receiving intravesical Bacille Calmette-Guerin (Connaught strain, 80
      mg/50 ml) over a 9-week induction course and each week for 3 weeks at 3, 6 and 12
      months. Outcome measures were recurrence rate, time to first recurrence and
      progression rate. Treatment-related complications were also evaluated. RESULTS:
      Seventy-two participants were enrolled, 36 for each group, 17 in Group A
      developed disease recurrence versus 25 of those in Group B (p < 0.05). There was
      no statistically significant difference in mean time to the first recurrence
      (Group A, 4.2 months; Group B, 4.1 months; p > 0.05). Seven of 17 (41%) patients
      in Group A and 16 of 25 (64%) patients in Group B had disease progression and
      underwent radical cystectomy (p < 0.05). Both intravesical administrations were
      generally well tolerated. CONCLUSION: Thiotepa is a promising intravesical agent
      for treatment of non-muscle invasive bladder cancer.

PMID- 24917737
TI  - A unique case of bilateral synchronous testicular tumor with concomitant
      bilateral diffuse intratubular germ cell neoplasia: testis sparing surgery and
      local radiotherapy.
AB  - Synchronous bilateral testicular germ cell tumors (TGCTs) are seen in exteremely
      rare cases. Although there is still no standard therapy for bilateral TGCTs,
      bilateral orchiectomy is recommended as the gold standard treatment.
      Nevertheless, it has some long-term problems, such as infertility and
      psychosocial difficulties, and thus some clinicians prefer to perform testis
      sparing surgery in appropriate cases. We reviewed the first case of bilateral
      synchronous TGCT with concomittant bilateral diffuse intratubular germ cell
      neoplasia in a young single patient, who was treated by a left radical
      orchiectomy and right testis sparing-surgery with following local radiotherapy to
      the right residual testicular tissue with previous semen cryopreservation to
      maintain the ability to father children. We supposed that testis-sparing surgery
      can be a feasible therapeutic alternative to radical orchiectomy in patients with
      bilateral TGCTs in terms of improving the quality of life and continuing
      fertility and normal hormonal status with no medications. However, while the long
      term effects are not yet known, this type of treatment should be perpormed in
      carefully selected cases with longlife expectancy. 

PMID- 24917738
TI  - The epidemiology and risk factors for renal cancer.
AB  - BACKGROUND: Renal cancer is a frequently occurring malignancy with over 270,000
      new cases diagnosed and it being responsible for 110,000 deaths annually on a
      global basis. Incidence rates have gradually increased whilst mortality rates are
      starting to plateau. OBJECTIVE: To review epidemiology and risk factors for renal
      cancer. METHODS: The current data is based on a thorough review of available
      original and review articles on epidemiology and risk factors for renal cancer
      with a systemic literature search utilising Medline. RESULTS: The prevalence of
      associated risk factors such as genetic susceptibility, smoking, hypertension and
      obesity are changing and could account for the changes in incidence whilst the
      role of diet and occupational exposure to carcinogens requires further
      investigation. CONCLUSION: Despite the evidence of various associated risk
      factors, further work is required from well designed studies to gain a greater
      understanding of the etiology of renal cancer.

PMID- 24917739
TI  - Prostate specific antigen: the past, present and future.
AB  - AIM: To review current data available on use of prostate specific antigen for
      screening healthy men for prostate cancer. METHODS: Literature was reviewed and
      the guidelines from, American cancer Society, American Urologic Association was
      reviewed. RESULTS: Current screening protocols lead to over diagnosis of prostate
      cancer. This often results in unnecessary biopsy procedures and treatments.
      CONCLUSION: We must consider the benefit of screening and treatment with the
      harms of over diagnosis and over treatment. Newer imaging modalities like
      magnetic resonance imaging have to be evaluated further.

PMID- 24917741
TI  - A prospective study of the role of inflammation in bladder cancer.
AB  - INTRODUCTION: To examine the role of inflammation in bladder cancer, we assessed
      the relationship between a systemic inflammation prognostic score (modified
      Glasgow Prognostic Score, mGPS), the tumor inflammatory cell infiltrate as
      measured by the Klintrup-Makinen score and tumor necrosis with cancer specific
      survival in patients with bladder cancer. MATERIALS AND METHODS: The cohort
      consisted of 68 bladder cancer patients, 47 with localised disease and 21 with
      muscle invasive disease. The mGPS response was constructed by measuring C
      reactive protein and albumin concentrations and the Klintrup-Makinen score was
      evaluated histologically for the local inflammatory response. Pathological
      parameters such as grade, T stage and tumor necrosis were also assessed. RESULTS:
      Median follow was 47 months and 24 patients died of their disease. On univariate
      analysis, T stage (p < 0.001), grade (p < 0.001) and mGPS (p = 0.002) were
      significant predictors of cancer specific survival. On multivariate analysis, T
      stage (hazard ratio 5.98, 95% confidence interval 3.18-11.24, p < 0.001) and mGPS
      (hazard ratio 1.78, 95% confidence interval 1.09-2.9, p = 0.02) were significant
      independent predictors of cancer specific survival. CONCLUSION: A preoperative
      systemic inflammatory response is an independent predictor of poor cancer
      specific survival in patients with bladder cancer.

PMID- 24917740
TI  - Sex differences in the physiology and pharmacology of the lower urinary tract.
AB  - Sexual dimorphism is not only noticed in the prevalence of many diseases, but
      also in multiple physiological functions in the body. This review has summarized
      findings from published literature on the sex differences of the pathophysiology
      and pharmacology of the lower urinary tract (LUT) of humans and animals. Sex
      differences have been found in several key areas of the LUT, such as overactive
      bladder, expression and function of neurotransmitter receptors in the bladder and
      urethra, and micturition patterns in humans and animals. It is anticipated that
      this review will not only evoke renewed interest for further research on the
      mechanism of sex differences in the pathophysiology of the LUT (especially for
      overactive bladder), but might also open up the possibilities for gender-based
      drug development by pharmaceutical industries in order to find separate cures for
      men and women with diseases of the LUT. 

PMID- 24917742
TI  - Variable correlation of grid coordinates to core location in template prostate
      biopsy.
AB  - PURPOSE: Transperineal template prostate biopsy has been proposed to facilitate
      systematic biopsy in patients undergoing repeat biopsy who are at high risk for
      cancer. Advocates tout the reliability of the grid to define biopsy location
      compared to hand-held transrectal ultrasound guided biopsy. However, accuracy of
      the biopsy needle depends on bevel position, tissue deformity, and technique. Due
      to this potential for error, we sought to determine whether the use of
      transperineal template biopsy would assure reproducibly accurate needle
      placement. MATERIALS AND METHODS: A standard 0.5 cm brachytherapy grid was
      utilized for transperineal biopsy. A single grid hole was used to obtain
      biopsies. The bevel of the needle was rotated to a different position with each
      biopsy, and the angle of the needle was varied to test the ability of the grid to
      "map" the prostate. RESULTS: We observed wide variation of needle location
      through a single brachytherapy grid hole. We are able to show that at 5 cm depth,
      an area of 2.47 mm(2) is possible to biopsy and at a depth of 25 cm;
      approximately 7.56 mm(2) is possible to biopsy. This gives a precision of biopsy
      of at the most shallow depth 22% and at the deepest 7%. CONCLUSION: There is
      potential for technical and equipment associated error with transperineal
      template guided prostate biopsy. The grid alone can account for substantial
      sources of error, so technique remains critical if the grid coordinates are to be
      used to predict presence or extent of cancer.

PMID- 24917743
TI  - In vitro regulation of cell growth and angiogenesis by inositol hexaphosphate in
      bladder cancer.
AB  - BACKGROUND: Inositol Hexaphosphate (IP6) is a naturally occurring
      polyphosphorylated carbohydrate that is found in food sources high in fiber
      content. We hypothesized that IP6 would inhibit the cell growth rate of bladder
      cancer in vitro. METHODS: T24 and TCCSUP bladder cancer cell lines were treated
      with titrating doses of IP6 (0.3, 0.6 and 0.9 mM/well). Cell viability and
      vascular endothelial growth factor levels were measured. RESULTS: Significant
      reductions (p < 0.001) in cellular growth were noted in both cell lines at all
      doses and time points tested, with the exception of 0.3 mM IP6 at 24 hours in the
      T24 cell line. The percent inhibition of vascular endothelial growth factor was
      significantly higher than that observed in the TCCSUP cell line at 48 and 72
      hours with 0.3 mM IP6 (p < 0.001). The T24 cells exhibited the same level of
      inhibition at 24 and 48 hours with 0.6 mM dose of IP6 and at 72 hours with the
      0.3 mM dose (p < 0.001). CONCLUSIONS: In vitro treatment of bladder cancer with
      the common dietary polyphosphorylated carbohydrate IP6 significantly decreased
      cellular growth by anti-angiogenic mechanisms. We feel that this data warrants
      further investigation and consideration for initiation of clinical trials to
      evaluate the safety and clinical utility of this agent.

PMID- 24917744
TI  - An innovative wound retractor/protector for prosthetic urologic surgery.
AB  - OBJECTIVE: We demonstrate an innovative use of a barrier surgical wound
      retractor/protector system for use in a variety of prosthetic urologic procedures
      (penile prosthetics, artificial urinary sphincters, male slings). MATERIALS AND
      METHODS: We demonstrate the use of a self-retaining ring wound retractor in a
      multitude of prosthetic urological procedures: insertion of an inflatable penile
      prosthesis through an infrapubic approach as well as penoscrotal approach,
      placement of a transperineal artificial urinary sphincter, and placement of a
      male urethral sling. RESULTS: The self-retaining ring wound retractor facilitated
      a more rapid setup and takedown, provided 360 degrees of atraumatic retraction as
      well as 360 degrees of wound protection, allowed for maximum exposure with a
      minimum incision size, significantly shortened the operating wound depth thus
      maximizing exposure, and isolated the surgical field minimizing prosthesis to
      skin contact. CONCLUSION: Our experience shows that prosthetic urologic surgeries
      can be enhanced with the use of the self-retaining ring wound retractor as it
      provides better surgical exposure, lowers wound infection risks, sets up more
      quickly as a safer retraction system with substantial cost savings.

PMID- 24917745
TI  - Laparoscopic Varicocelectomy Carried Out with the LigaSure Device in 52 Patients.
AB  - We describe the effective use of the bipolar vessel-sealing device: LigaSure for
      the division of the internal spermatic vessels in a laparoscopic varicocelectomy.
      A total of 52 males with varicocele (left-side n = 49, and bilateral n = 3) were
      included in this study. Blunt dissection was used to isolate the packet of
      spermatic vessels. The packet of spermatic vessels was divided using a bipolar
      diathermy system, the LigaSure Precise. It was clear that the operative time was
      significantly reduced compared to the method using clips, which was done before
      the development of this kind of device. In another experiment to examine the
      effect of vessel sealing, it was confirmed that the LigaSure has performance
      comparable to the clips. Despite the result that the Harmonic scalpel was less
      effective in vessel sealing, our study found it difficult to determine which is
      superior, LigaSure or clips, in terms of operative time, relapse rate and
      complication. 

PMID- 24917746
TI  - Bilateral ureteral tapering and secondary ureteroneocystostomy for late stenosis
      in a patient with bladder extrophy.
AB  - OBJECTIVE: To report a case of severe hydronephrosis 20 years after bladder
      exstrophy (BE) repair, managed by bilateral ureteral tapering and secondary
      ureteroneocystostomy. CASE PRESENTATION: A 21-year-old woman with a history of BE
      and ureteral reimplantation, presented with hematuria-dysuria syndrome and
      recurrent febrile urinary tract infections. After counselling, she elected to
      undergo bilateral ureteral tapering and second ureteroneocystostomy. CONCLUSION:
      Hydronephrosis secondary to ureteralvesical stricture in BE patients can be
      successfully managed with ureteral reimplantation associated to ureteral tapering
      even after a prior reimplantation.

PMID- 24917747
TI  - Recurrent dedifferentiated paratesticular liposarcoma with synchronous renal cell
      carcinoma and prostate cancer.
AB  - Paratesticular liposarcoma is a very rare cause of scrotal mass. It is thought
      that they arise from spermatic cord lipomas most commonly. While well
      differentiated tumors tend to share many histological similarities with
      dedifferentiated tumors, the latter has a much more aggressive phenotype. We
      present an unusual case of a 69-year-old male with synchronous prostate
      adenocarcinoma and unilateral renal cell carcinoma who was found to have a
      dedifferentiated paratesticular liposarcoma. Treatment was with radical
      resection, preserving the testis, followed by radiotherapy. Unusually recurrence
      did not occur until 4 years following initial treatment. This case demonstrates
      the high propensity of dedifferentiated liposarcoma to recur locally and examines
      the most frequently employed management strategies. 

PMID- 24917748
TI  - Single foci prostate cancer: current diagnosis and management.
AB  - Diagnosis of small prostate cancer foci is a real challenge for pathologists and
      urologists as it carries the risk of false positive or negative diagnosis with
      clinical consequences. Diagnosis of small prostate cancer foci requires a strict
      methodological approach which includes a search for major and minor features
      under low and high magnification. Ambiguous cases can be further clarified with
      the use of basal cell immunomarkers complemented by a positive indicator of
      malignancy. Despite the new diagnostic armamentarium, a few cases will continue
      to remain doubtful and might require an appropriate rebiopsy. 

PMID- 24917749
TI  - Percutaneous Nephrolithotomy in Autosomal Dominant Polycystic Kidney Disease: Is
      it Different from Percutaneous Nephrolithotomy in Normal Kidney?
AB  - OBJECTIVES: Nephrolithiasis has been reported in 20-28% of patients, of whom 50%
      are symptomatic for stone disease and 20% require definite urologic intervention.
      The management of nephrolithiasis includes oral alkali dissolution therapy,
      extracorporeal shock wave lithotripsy and surgical treatment. In such patients,
      percutaneous nephrolithotomy (PNL) as a method of stone treatment has been
      reported in few cases with limited experience. The aim of this study is to
      present our experience of PNL in autosomal dominant polycystic kidney disease
      (ADPKD) and assessing the outcome results. MATERIAL AND METHODS: From 2002 to
      2011, 22 patients (26 renal units) suffering from ADPKD with stone were managed
      by PNL. Demographic characteristics, operative parameters and postoperative
      complications were recorded and analysed. RESULT: The overall success rate of PNL
      was 82.1% and PNL with extracorporeal shock wave lithotripsy for clinically
      significant residual fragments was 92.85% respectively. The hematuria required
      blood transfusion (n = 9), postoperative fever due to cyst infection (n = 4) and
      paralytic ileus (n = 3) were recorded. CONCLUSION: The PNL in ADPKD PNL is safe
      and effective but have more postoperative complications such as bleeding
      requiring transfusions, fever due to cyst infection and paralytic ileus.

PMID- 24917750
TI  - pT0 Prostate Cancer: Predictive Clinicopathologic Features in an American
      Population.
AB  - INTRODUCTION: The pT0 stage of prostate cancer describes the radical
      prostatectomy (RP) specimen where no cancer can be identified. Given known racial
      and geographic differences in prostate cancer incidence and survival, we reviewed
      our experience with pT0 disease to determine applicability of these predictive
      features in an American population. MATERIALS AND METHODS: A retrospective chart
      review was conducted for all RPs at one state tertiary care institution during a
      20-year period (1991-2011). Clinicopathologic features of pT0 patients were
      collected and their relevant pathologic material re-reviewed. RESULTS: Of a total
      of 1,635 RPs performed, 4 (0.2%) not receiving neoadjuvant therapy or other prior
      prostate surgeries were stage pT0. Biopsies from 3 of 4 patients were re
      evaluated and confirmed a small focus, <1% of tissue, of Gleason score 3+3
      adenocarcinoma; a fourth was not available for re-review. Our re-review of the RP
      slides identified small foci of cancer in two of the four, thus yielding a final
      true pT0 incidence of 0.1%. Preoperative prostate specific antigen ranged from
      4.4 to 7.4 ng/ml, clinical stages were all T1c, and there was no evidence of
      recurrence at 3 months to 10 years of follow-up. CONCLUSIONS: Stage pT0 prostate
      cancer is very uncommon, occurring with an incidence of 0.1%, and in our
      experience occurs only in clinical T1c patients with pre-biopsy prostate specific
      antigen < 7.5 ng/ml, with Gleason score 3 + 3 adenocarcinoma comprising < 1%, 1
      mm of a single core biopsy, a stricter threshold than that seen in non-American
      populations.

PMID- 24917751
TI  - The use of a memokath prostatic stent for obstructive voiding symptoms after
      brachytherapy.
AB  - INTRODUCTION: Brachytherapy may be complicated by serious obstructive voiding
      symptoms (OVS). Only conservative treatment options are available in the first 6
      months after brachytherapy. We evaluated safety, efficacy and patient tolerance
      of the Memokath prostatic stent (MPS). MATERIAL AND METHODS: A MPS was placed in
      10 patients with OVS after brachytherapy. Evaluation included uroflowmetry,
      international prostate symptom score (IPSS), prostate volume and
      urethrocystoscopy before and 3 months after placement of the stent. RESULTS: Both
      the IPSS and uroflowmetry results significantly improved after stent insertion.
      The mean IPSS decreased from 29/5 to 11/1 and the mean Qmax from the uroflowmetry
      improved from 4.7 to 11.2 ml/s. The 5 patients who were catheter dependent voided
      spontaneously with a mean Qmax of 15 ml/s. Two stents migrated towards the
      bladder, and those patients needed a second stent which was placed without
      complications. Removal of the stent was easy to perform. Adverse effects were
      minor with perineal pain and irritative voiding symptoms occurring in 5 patients
      mainly in the first weeks after insertion. This did not negatively influence
      quality of life and all patients were more satisfied with the stent than without.
      CONCLUSIONS: The MPS provides a safe, effective, and completely reversible
      treatment for patients with OVS after brachytherapy and was well tolerated.

PMID- 24917752
TI  - Pathological Correlation between Number of Biopsies and Radical Surgery: Does It
      Make a Difference to Final Pathology?
AB  - AIMS: To evaluate whether the number of biopsies performed via transrectal
      ultrasound (TRUS) accurately predicts pathological parameters such as Gleason
      sum, prostatic intraepithelial neoplasia and perineural invasion of the final
      prostatectomy specimen. MATERIALS AND METHODS: The cohort consisted of 99
      patients whom had undergone radical prostatectomy. Comparisons were made between
      the number of biopsies utilised and the presence of the pathological parameters
      from tissue at time of diagnosis and tissue from the final prostatectomy.
      RESULTS: A significant difference was noted between Gleason sum, prostatic
      intraepithelial neoplasia and perineural invasion from tissue at time of
      diagnosis irrespective of the number of biopsies utilised and tissue from the
      radical specimen (p < 0.001, p < 0.001, p < 0.001 respectively). No difference
      was noted in the mean Gleason sum when 11-14 biopsies were utilised at TRUS and
      the Gleason sum from the radical specimen. CONCLUSION: We have demonstrated that
      the number of biopsies utilised at time of TRUS for diagnosis predicts the
      accuracy of pathological parameters in the final radical prostatectomy specimen.
      We believe that 11-14 biopsies should be utilised at time of TRUS as this allows
      a higher accuracy in the Gleason sum and therefore allows optimum treatment plans
      to be devised.

PMID- 24917753
TI  - Holmium Laser Enucleation of the Prostate: Comparison of Immediate Postoperative
      Outcomes in Patients with and without Antithrombotic Therapy.
AB  - OBJECTIVE: To compare the immediate postoperative outcomes of patients with
      benign prostatic hyperplasia undergoing Holmium laser enucleation of the prostate
      (HOLEP) with and without full anticoagulation or antiplatelet therapy at the time
      of surgery. MATERIALS AND METHODS: A retrospective review was performed on a
      series of consecutive patients undergoing HOLEP at our institution by a single
      surgeon from February 2004 to September 2010. Demographic, surgical, pathological
      and outcome data were collected. Two cohorts were identified on the basis of
      antithrombotic therapy at the time of surgery. Patients who continued on aspirin,
      aspirin/dipyridamole, clopidogrel and warfarin throughout the surgery were
      included in the antithrombotic cohort. Univariate analysis was performed to
      determine differences in outcomes between the 2 cohorts. RESULTS: Total 125
      consecutive patients underwent HOLEP with 52 patients on antithrombotic therapy
      at the time of surgery and 73 patients were not on antithrombotic therapy during
      surgery. Patients in the antithrombotic group were older (75.1 +/-7.5 vs. 71.7 +/
      8.3 years; p = 0.02) and had a higher median ASA physical status (3 (3-3) vs. 2
      (2-3), p < 0.0001). The mean operating time and median specimen volume were not
      significantly different between the 2 cohorts. The median length of stay (2 (1-3)
      vs. 1 (1-2) d, p = 0.014) was longer in the antithrombotic cohort. The
      transfusion rate (7.7 vs. 0%, p = 0.028) was predictably higher in the
      antithrombotic cohort. No patients required re-operation for bleeding.
      CONCLUSIONS: The use of HOLEP in patients on antithrombotic therapy is safe
      despite the higher surgical risk profile of that particular patient population
      and the potential increased risk for significant bleeding.

PMID- 24917754
TI  - Novel Use of AngioVac System to Prevent Pulmonary Embolism during Radical
      Nephrectomy with Inferior Vena Cava Thrombectomy.
AB  - Venous tumor thrombus occurs in 5-10% of patients with renal cell carcinoma.
      Surgical excision offers the best chance for survival, but is technically
      difficult. Risk of pulmonary embolism from venous thrombus or tumor thrombus is
      high, especially with tumors located higher in the inferior vena cava.
      Cardiopulmonary bypass may be used when a tumor extends above the diaphragm, but
      carries significant risk. We present an 86-year-old woman with a 7 cm renal mass
      extending into the inferior vena cava just below the confluence of the hepatic
      vessels. Prior to surgery she was found to have increasing pulmonary embolisms
      despite appropriate anticoagulation. Intraoperatively, the AngioVac aspiration
      system was utilized to prevent further pulmonary embolism. This is the first
      reported case of the use of this system during radical nephrectomy. 

PMID- 24917755
TI  - A benign renal cyst containing liesegang rings mimicking a renal cell carcinoma:
      a case report.
AB  - Liesegang rings are uncommon pathological findings which may cause diagnostic
      dilemmas for pathologists. Awareness of their appearance is important to avoid
      over diagnosis of parasitic infection, algal contamination and psammoma bodies.
      Liesegang rings are benign, lamellar structures with radial striations and a
      central amorphous core. They are found in a variety of tissues and fluids in both
      an intra- and extra-cellular sites. We present here a case of a cystic renal
      lesion containing Liesegang rings mimicking a renal cell carcinoma. 

PMID- 24917756
TI  - Laparoscopic resection of retroperitoneal neural tumors.
AB  - PURPOSE: Retroperitoneal neural tumor (RNT) is rarely excised laparoscopically,
      and the laparoscopic management of RNT remains controversial. We herein report 4
      cases of laparoscopic excision of RNT that resulted in diverse clinical outcomes.
      PATIENTS AND METHODS: Between August 2005 and January 2011, we performed
      laparoscopic excision of RNT in 4 patients. The mean tumor size was 4.5 cm. The
      mean operative time was 297 minutes and the mean amount of blood loss was 55 ml.
      The surgeries were uneventful, with no operative complications or evidence of
      intra-abdominal bleeding. However, 2 patients required reoperation for delayed
      hemorrhage and urinoma formation, respectively. RESULTS: The postoperative
      pathological diagnoses were schwannoma in 3 patients and ganglioneuroblastoma in
      1 patient. All patients were well with no signs of peripheral neuropathy or
      radiculopathy, and CT and/or (18)F-FDG PET/CT performed during follow-up
      indicated no evidence of disease. CONCLUSIONS: Obtaining extensive preoperative
      knowledge of the source neural and vascular anatomy of the tumor is important for
      the surgical planning of laparoscopic resection of RNT. When a great deal of care
      is taken to divide the tumor and the source nerves and vital vessels, safe
      execution of RNT can be achieved for minimal postoperative mortality and
      morbidity.

PMID- 24917757
TI  - Penile incarceration with metallic foreign bodies: management and review of
      literature.
AB  - INTRODUCTION: Penile strangulation from constricting metallic objects disorders
      is an uncommon urological emergency which requires prompt intervention to prevent
      complications. The treatment modalities are diverse and characterized by lack of
      consensus. MATERIAL AND METHODS: Three cases with penile incarceration due to
      constricting metallic objects who presented to our department were included in
      this study. All 3 patients required different management options highlighting the
      diversity of clinical presentation and need for customization of treatment as per
      the clinical scenario. RESULTS: The 3 patients required different approach for
      treatment. First patient could be managed by degloving of penile skin while
      second patient required mechanical removal of the foreign body and debridement of
      local necrotic tissues. The third patient had to undergo excision of gangrenous
      penile skin and skin grafting. CONCLUSION: The study emphasizes the diversity of
      clinical presentations and the need for employing different surgical techniques
      to achieve the desired results.

PMID- 24917758
TI  - Cavernosal Abscess due to Streptococcus Anginosus: A Case Report and
      Comprehensive Review of the Literature.
AB  - Corpus cavernosum abscesses are uncommon with only 23 prior reports in the
      literature. Several precipitating factors for cavernosal infections have been
      described including injection therapy for erectile dysfunction, trauma, and
      priapism. Common causal organisms include Staphylococcus aureus, Streptococci,
      and Bacteroides. We report a unique case of a corpus cavernosum abscess due to
      proctitis with hematological seeding and review the literature on cavernosal
      abscesses. 

PMID- 24917759
TI  - Significance of random bladder biopsies in non-muscle invasive bladder cancer.
AB  - BACKGROUND/AIMS: To evaluate retrospectively the clinical outcome of random
      bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC)
      undergoing transurethral resection (TUR). PATIENTS AND METHOD: This study
      included 234 consecutive patients with NMIBC who underwent random biopsies from
      normal-appearing urothelium of the bladder, including the anterior wall,
      posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra,
      during TUR. RESULT: Thirty-seven patients (15.8%) were diagnosed by random
      biopsies as having urothelial cancer. Among several factors available prior to
      TUR, preoperative urinary cytology appeared to be independently related to the
      detection of urothelial cancer in random biopsies on multivariate analysis.
      Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8%
      positive predictive value and 89.3% negative predictive value for predicting the
      findings of the random biopsies. CONCLUSION: Biopsies of normal-appearing
      urothelium resulted in the additional detection of urothelial cancer in a
      definite proportion of NMIBC patients, and it remains difficult to find a
      reliable alternative to random biopsies. Collectively, these findings suggest
      that it would be beneficial to perform random biopsies as part of the routine
      management of NMIBC.

PMID- 24917760
TI  - The accuracy of magnetic resonance imaging in radical prostatectomy.
AB  - AIMS: The aim of this study was to examine the accuracy of standard magnetic
      resonance imaging (MRI) in the localised staging of prostate cancer in those who
      had undergone radical prostatectomy. PATIENTS AND METHODS: The cohort consisted
      of 110 patients who had undergone MRI for staging of prostate cancer and
      subsequently underwent radical prostatectomy. T stage was analysed both on MRI
      and from the specimen following radical surgery. RESULTS: Of the patients 57% of
      patients had their disease up-staged following radical surgery from preoperative
      MRI findings. Of those patients who had their disease up-staged following
      surgery, nearly 50% of patients had gone from organ confined disease at time of
      MRI to extra-prostatic involvement from the surgical specimen. CONCLUSION: We
      have reported that MRI has a wide range of accuracy. Given developments in MRI
      technologies further work should be pursued to help in the staging of this
      disease for which decision to treat is difficult.

PMID- 24917761
TI  - Prevalence of circulating tumor cells in localized prostate cancer.
AB  - BACKGROUND: Circulating tumor cells (CTC) predict overall survival in patients
      with metastatic prostate cancer. The objective of this study is to measure CTC
      before radical prostatectomy in intermediate- and high-risk prostate cancer
      patients. MATERIALS AND METHODS: The study accrued 12 patients and 10 provided
      adequate peripheral blood sample. Blood was drawn preoperatively and assayed for
      CTC using the CellSearch system. Patients were categorized as CTC positive (>= 1
      CTC) or CTC negative (no CTC). RESULTS: Median age was 64.5 years (range 49-77
      years), median prostate specific antigen was 7.4 ng/ml (range 5.7-25.7 ng/ml).
      Seven patients had intermediate-risk and 3 patients had high-risk prostate
      cancer. One patient was found to be CTC positive. CONCLUSIONS: Our pilot study
      shows that CTC are rare in patients with clinically localized disease despite
      intermediate- to high-risk features. CTC may not be the optimal marker to predict
      prognosis or detect residual disease after radical prostatectomy.

PMID- 24917762
TI  - Predictive factors for benign lesions in partially or radically resected kidneys
      in a single independent cancer center.
AB  - OBJECTIVE: To assess the incidence and predictive factors of benign renal lesions
      in surgical specimens obtained at our institution. METHODS: We carried out a
      retrospective assessment of 96 renal nodules, diagnosed by dynamic multi-detector
      row helical computed tomography, and resected by either radical or partial
      nephrectomy between January 2004 and November 2011. The incidence of benign
      lesions in 1-cm increments of diameter was determined and the predictive factors
      for these lesions were then evaluated. RESULTS: Of the 96 nodules, histology
      confirmed that 13 (13.5%) were benign. The incidence of benign lesions was 25.0%
      for nodules <1 cm, 23.8% for nodules 1-1.9 cm, 11.5% for nodules 2-2.9 cm, 7.7%
      for nodules 3-3.9 cm, and 7.1% for nodules >=4 cm. Multivariate analysis showed
      that younger age (<60 years; odds ratio [OR] = 5.23), female gender (OR = 4.78),
      and smaller nodule size (<3 cm; OR = 6.14) were significant predictive factors
      for benign lesions. CONCLUSIONS: The incidence of benign lesions in this study
      (13.5% of total cases) was relatively low compared with recent studies from
      Western countries that reported an incidence of 15-20%. Significant predictive
      factors for benign lesions included younger age, female gender, and smaller tumor
      size.

PMID- 24917763
TI  - Transperitoneal transvesical laparoscopic repair of vesicovaginal fistulae:
      experience of a tertiary care centre in northern India.
AB  - OBJECTIVE: To present our experience of treating supratrigonal vesicovaginal
      fistulae by laparoscopic technique and their long-term follow-up. MATERIAL AND
      METHODS: Between January 2008 and June 2012, 28 cases of supratrigonal fistulas
      were repaired by laparoscopic transperitoneal transvesical technique with
      interposition flap. The obstetric fistula was present in 18 and gynecologic
      fistula in 10 patients. Single supratrigonal fistula was present in 26 patients
      and in 2 patients there were 2 fistulae lying side to side. The vaginal opening
      was closed as single layer interrupted suture and cystotomy closed as single
      layer continuous suture by 3-0 polygalactin. The omentum was used as
      interposition flap in all except 2 cases in whom postero-superior vesical fold of
      peritoneum was used. The open conversion was required in 2 cases. The urethral
      catheter was removed in 4 weeks following a micturating cystogram. RESULT: The
      mean fistula size was 1.2 cm (range 0.8-2.5 cm). Open conversion was performed in
      2 cases of whom one had excess carbon-dioxide retention and cardiac arrhythmia
      and in another case the needle of 3-0 polygalactin was avulsed and lost in
      peritoneal cavity which was recovered following laparotomy. All patients were
      continent following the catheter removal. The median follow-up is 24 months. None
      developed any complication related to laparoscopic repair till last follow-up.
      CONCLUSION: Laparoscopic repair of supratrigonal vesicovaginal fistulae is an
      effective and safe minimally invasive treatment with excellent result.

PMID- 24917764
TI  - Prospective Randomized Comparison of Open versus Transperitoneal Laparoscopic
      Ureterolithotomy: Experience of a Single Center from Northern India.
AB  - AIM: Prospective randomized study on transperitoneal laparoscopic
      ureterolithotomy (TPLU) versus open ureterolithotomy (OU) for treatment of large
      impacted ureteric stones (>= 1.5 cm) and assessment of overall results. MATERIAL
      & METHODS: In a prospective study between 2010 to 2012, 30 patients underwent
      TPLU and 30 OU based on 1:1 randomization. The operation was indicated primarily
      in 44 cases or after failed shock-wave lithotripsy/ureteroscopy in 16 cases. Two
      groups were compared for operative time, success rate, visual pain score,
      analgesic requirement, hospital stay, and postoperative complications.
      Statistical analysis was performed with SPSS(r) version 16.0 using Fisher exact
      or Mann-Whitney U tests with p < 0.05 considered statistically significant.
      RESULTS: The difference in visual pain score (6.2 in TPLU group vs 3.1 in OU
      group on day 1; 4.8 vs. 2.4 on day 2) and tramadol requirements (184.32 mg in
      TPLU group vs. 150.87 mg in OU group on day 1; 97.34 mg vs. 65.56 mg on day 2)
      were statistically significant and more in OU. Hospital stay and convalescence
      were significantly lower in the TPLU. However, stone removal in one attempt was
      similar in both the groups. CONCLUSION: Although successful stone removal rates
      are equal in both groups, TPLU is associated significantly with less
      postoperative pain, less analgesic requirement, shorter hospital stay and short
      convalescence in comparison to OU.

PMID- 24917766
TI  - Urethtral approach in retroperitoneoscopic radical prostatectomy: a novel
      technique for safe prostate dissection.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic radical prostatectomy (LRP) remains
      technically challenging and is associated with a steep learning curve. Prostate
      apex dissection (PAD) is one the most challenging elements of LRP. This study
      describes a novel technique for PAD using a transurethral approach (urethral
      assistance). METHODS: Through the transurethral route, Young's foreign body
      forceps is introduced under laparoscopic vision and both vas deferens are grasped
      for efficient traction of the prostate. The forceps is quickly clamped to the
      laparoscope holder. Urethral assistance facilitates more efficient dissection
      during dissection of the bladder neck, vas deferens, and seminal vesicles,
      transaction of the posterior prostatovesical junction, mobilization of the
      prostate off the rectum, and ligation of the dorsal venous complex. RESULTS: In
      10 patients with localized prostate cancer who underwent LRP using the urethral
      assistance technique, sufficient retraction of the prostate was maintained in the
      appropriate direction. No complications related to urethral assistance were
      observed. No internal or external instrument collisions occurred during PAD.
      CONCLUSION: Urethral assistance provides a simple, reliable, cost-effective
      approach for performing PAD during LRP.

PMID- 24917765
TI  - Can the R.e.N.a.L nephrometry score preoperatively predict postoperative clinical
      outcomes in patients undergoing open and laparoscopic partial nephrectomy?
AB  - AIM: We evaluate whether the preoperative R.E.N.A.L Nephrometry Score (RNS) can
      predict the postoperative outcomes in patients undergoing either an open or
      laparoscopic partial nephrectomy. PATIENTS AND METHODS: We retrospectively
      calculated the RNS of 128 patients who underwent either an open partial
      nephrectomy (OPN) (n = 38) or laparoscopic partial nephrectomy (LPN) (n = 90)
      between 2003 and 2011. Patients were categorized into low, moderate or high
      complexity groups based on RNSs. Intra-operative warm ischemic time (WIT), peri
      operative surgical outcomes using the Clavien-Dindo classification, postoperative
      histology, positive surgical margin rates were correlated to the RNS. RESULTS:
      The RNS was associated with the length of the WIT in OPN (low vs. moderate vs.
      high: 11.4 vs. 13.1 vs. 23.4 minutes, p = 0.025) and blood loss in LPN (low vs.
      moderate 319 vs. 498 ml, p = 0.009). The positive surgical margins were greater
      in high versus moderate RNS lesions (40 vs. 7.4%, p = 0.045). No differences were
      seen in complications, hospital stay or transfusion rates. The RNS was
      significantly higher in OPN versus LPN (7.45 vs. 6.2, p = 0.0002). CONCLUSION: An
      Increasing RNS was associated with increased WIT in OPN and blood loss in LPN,
      supporting RNS relationship to tumor complexity. A higher RNS in OPN indicate it
      may corroborate procedure choice. RNS should allow comparisons between treatment
      modalities for similar complexity lesions and with further research could aid
      stratification of individual risk preoperatively.

PMID- 24917767
TI  - A 52-year-old male with bilaterally duplicated collecting systems with
      obstructing ureteral stones: a case report.
AB  - Collecting system duplication is marked by a variety of clinical syndromes.
      Bilateral and obstructed duplicated systems, particularly with asymmetric levels
      of duplication, are rare and typically due to ureteric bud development anomalies.
      The infrequency with which this condition exists makes it a formidable challenge
      for physicians and patients. To our knowledge, we present the first case report
      of bilateral obstruction of bilaterally duplicated collecting systems. In our
      case, a 52-year-old male complaining of low back pain, constipation, urinary
      urgency and hematuria was found to have bilateral obstructing stones as well as
      asymmetrical bilateral collecting system duplication. We discuss the natural
      history of this condition, its consequences and identification. 

PMID- 24917768
TI  - Testicular vasculitis - literature review and case report in queensland.
AB  - A 21-year-old male presented with acute onset, sharp right sided testicular pain.
      The testicle was removed with a histological diagnosis of testicular vasculitis.
      Anti-neutrophil cytoplasmic antibodies were negative. Although rare, males who
      present with acute onset pain should be screened for testicular vasculitis with a
      scrotal ultrasound and blood investigations including tumor markers and anti
      neutrophil cytoplasmic antibodies. 

PMID- 24917769
TI  - Massive abdominoscrotal hydrocele.
AB  - Abdominoscrotal hydrocele (ASH) is a very rare clinical finding. It is
      characterized by a large scrotal hydrocele in communication with the abdominal
      cavity through the inguinal canal. Most reports of ASH have been in the pediatric
      population. We present the case of a 67-year-old man, with severe liver disease,
      who was discovered to have massive bilateral ASH secondary to ascites. 

PMID- 24917770
TI  - Pulmonary Complications following Percutaneous Nephrolithotomy: A Prospective
      Study.
AB  - INTRODUCTION: Pulmonary complications may occur in the post-operative period and
      are a significant cause of morbidity and mortality in patients undergoing
      anesthesia and surgery. Complication rates vary according to different procedures
      and different types of anesthesia and may be affected by the patient condition.
      The purpose of this study was to examine pulmonary complications following
      percutaneous nephrolithotomy (PCNL) and to search for associations between the
      pre- and intra-operative factors and the risk of post-operative pulmonary
      complications (PPC). PATIENTS AND METHODS: This was a prospective observational
      study of 100 consecutive adult patients who underwent PCNL surgery. We collected
      data of the patient, surgery and anesthesia and analyzed it to find correlations
      with PPC. RESULTS: Eight (8%) patients had PPC following PCNL, 7 patients had
      pneumothorax and 1 had atelectasis and pleural effusion. The latter patient died
      at post-operative day 24 due to respiratory failure. It was found that patients
      who had PCNL on the right kidney were at lower risk for PPC. In addition it was
      found that younger patients had a higher incidence of PPC. CONCLUSIONS: Based on
      this study the most common type of post-operative complication following PCNL is
      pulmonary, with pneumothorax being the main complication. PPC may result in
      patient mortality. The side of the operation and the patient's age might affect
      the risk of PPC.

PMID- 24917772
TI  - Considerations in minimally invasive surgery for renal and ureteric calculi: a
      bicenter quality control study.
AB  - BACKGROUND: The use of minimally invasive surgery is increasing. Evaluating the
      quality of care brings new sights in the optimization of operating techniques.
      METHODS: We included all procedures performed in two hospitals during 2010 and
      2011. A total of 264 patients were included in the ureterorenoscopy (URS) group
      and 77 patients in the percutaneous nephrolitholapaxy (PCNL) group. Data were
      gathered by retrospectively reviewing medical records. RESULTS: Mean stone
      diameter in the URS group was 9 mm. Patients suffered from a single stone in 79%
      of the cases. Calculi in the distal ureter, defined as the part of the ureter
      below the lower border of the sacroiliac joint, were most likely to be removed. A
      stone-free status was reached in 69% of the cases using URS. Mean stone diameter
      in the PCNL group was 23 mm. PCNL was successful in 70% of the cases in Haga
      Hospital versus 53% in Medisch Centrum Haaglanden. Incidence of complications was
      comparable between the hospitals (p = 0.5). Outcome and quality of both PCNL and
      URS was not influenced by sex, age or body mass index. CONCLUSION: The clinical
      results were comparable with results in the literature. Further improvement can
      be made by optimization of technical aspects and centralization of treatment by
      urologists experienced in minimally invasive techniques.

PMID- 24917771
TI  - Preliminary study of percutaneous nephrolithotomy on an ambulatory basis.
AB  - OBJECTIVE: Preliminary study to assess the feasibility and safety of percutaneous
      nephrolithotomy (PCNL) as an ambulatory procedure. PATIENTS AND METHODS: Between
      February 2011 and September 2012, 84 patients with renal calculi fulfilling the
      inclusion criteria were admitted to the Urology Department of Benha University
      Hospitals for PCNL. All patients were subjected to a full medical history,
      clinical, laboratory and radiological examinations. Tubeless PCNLs were done in
      the supine position, and an antegrade double-J stent was inserted. Operative time
      and intraoperative complications were recorded. Postoperatively, the hematocrit
      value, postoperative pain and analgesics, need of blood transfusion, stone-free
      rate, and length of hospital stay were recorded. Stable patients that could be
      safely discharged within 24 hours after surgery were considered ambulatory.
      RESULTS: All cases of tubeless PCNL were successfully done and no cases converted
      to open surgery. The overall stone-free rate was 91.7%, the mean postoperative
      pain score measured by the visual analog scale was 4.4 +/- 1.2, the mean overall
      hematocrit deficit was 4.8 +/- 2.2% and the mean hospital stay was 33.4 +/- 17.5
      hours. Ambulatory PCNL was accomplished in 60 out of 84 patients (71.4%) and
      double-J stents were removed 7-10 days postoperatively. In the non-ambulatory
      cases, double-J stents were removed after auxillary procedures were done
      according to each case. CONCLUSION: PCNL can be safely done on an ambulatory
      basis under strict criteria, but further studies are needed to confirm and expand
      these findings.

PMID- 24917773
TI  - The use of the amplatz sheath in percutaneous nephrolithotomy: does amplatz
      sheath size matter?
AB  - OBJECTIVES: To evaluate the effect of Amplatz sheath size used in percutaneous
      nephrolithotomy (PCNL) on postoperative outcome, bleeding, and renal impairment
      rates. MATERIALS AND METHODS: One-hundred and ten patients who underwent
      uneventful percutaneous nephrolithotomy between November 2011 and October 2012
      were included in the study. The patients were divided into 5 groups based on
      Amplatz sheath size (22, 24, 26, 28 and 30 Fr). Groups were comppared in terms of
      pre- and post-operative mean hemoglobin, creatinine, nephrostomy time,
      nephrostomy tube diameter, operative time, and fluoroscope time. RESULTS: Mean
      operative time, preoperative hemoglobin and creatinine values were similar in all
      groups. Postoperative mean hemoglobin level was significantly lower and
      postoperative mean creatinine level was significantly higher in patients who were
      treated with a larger Amplatz sheath when compared to a smaller size (p < 0.05).
      It was observed that nephrostomy time and nephrostomy tube size significantly
      increased as the Amplatz sheath size increased. Seven patients presented with
      postoperative infection (1, 2, 1, 0 and 3 patients in Group I, II, III, IV, and V
      respectively), 13 patients presented with bleeding requiring blood transfusion
      (2, 4, and 7 patients in Group III, IV, and V respectively), and residual stone
      was observed in 9 patients (5, 2, 0, 1, and 1 patients in Group I, II, III, IV,
      and V respectively). CONCLUSION: Although the use of a larger Amplatz sheath for
      larger stones seems to be suitable, this is not the case for smaller stones. For
      smaller stones, a smaller Amplatz sheath size would be useful to decrease the
      bleeding and renal impairment rates.

PMID- 24917774
TI  - Use of BioGlue Surgical Adhesive in Hypospadias Repair.
AB  - PURPOSE: To prospectively evaluate the efficacy of albumin glutaraldehyde tissue
      adhesive (BioGlue) in the surgical treatment of patients with hypospadias.
      MATERIALS AND METHODS: Two groups of 20 patients each who underwent hypospadias
      repair were included in the study. In the first group we utilized BioGlue as an
      additional protective layer to the suture line of the neo-urethra, while patients
      in the second group were operated on utilizing a routine surgical technique.
      RESULTS: There were no statistical differences between patients from the 2 groups
      in terms of surgical complications. Urethrocutaneous fistula was revealed in 4
      (20%) patients after repair with BioGlue and in 3 (15%) patients from the control
      group (p = 0.686), suture line breakdown in 4 (20%) and in 1 (5%) patients (p =
      0.478), meatal stenosis in 1 (5%) and in 1 (5%) patient (p = 1). Furthermore more
      patients in the BioGlue group (n = 12, 60%) demonstrated poor cosmetic results
      compared to the control group where most patients - 19 (95%) had acceptable
      cosmetic outcomes (p = 0.007). CONCLUSIONS: Our data showed no benefits of
      BioGlue use in hypospadias repair.

PMID- 24917775
TI  - Developing a robotic prostatectomy service and a robotic fellowship programme -
      defining the learning curve.
AB  - INTRODUCTION: Robotic radical prostatectomy (RRP) is an established treatment for
      prostate cancer in selected centres with appropriate expertise. We studied our
      single-centre experience of developing a RRP service and subsequent training of 2
      additional surgeons by the initial surgeon and the introduction of United
      Kingdom's first nationally accredited robotic fellowship training programme. We
      assessed the learning curve of the 3 surgeons with regard to peri-operative
      outcomes and oncological results. PATIENTS AND METHODS: Three hundred consecutive
      patients underwent RRP between November 2008 and August 2012. Patients were
      divided into 3 equal groups (Group 1, case 1-100; Group 2, case 101-200; and
      Group 3, case 201-300). Age, ASA score, preoperative co-morbidities and
      indications for laparoscopic radical prostatectomy were comparable for all 3
      patient groups. Peri-operative and oncological outcomes were compared across all
      3 groups to assess the impact of the learning curve for laparoscopic radical
      prostatectomy. All surgical complications were classified using the Clavien-Dindo
      system. RESULTS: The mean age was 60.7 years (range 41-74). There was a
      significant reduction in the mean console time (p < 0.001), operating time (p <
      0.001), mean length of hospital stay (p < 0.001) and duration of catheter (p <
      0.001) between the 3 groups as the series progressed. The two most important
      factors predictive of positive surgical margins (PSM) at RRP were the initial
      prostate specific antigen (PSA) and tumor stage at diagnosis. The overall PSM
      rate was 26.7%. For T2/T3 tumors the incidence of PSM reduced as the series
      progressed (Group 1-22%, Group 2-32% and Group 3-26%). The incidence of major
      complications i.e. grade Clavien-Dindo system score <= III was 2% (6/300).
      CONCLUSION: RRP is a safe procedure with low morbidity. As surgeons progress
      through the learning curve peri-operative parameters and oncological outcomes
      improve. This learning curve is not affected by the introduction of a fellowship
      training programme. Using a carefully structured mentored approach, RRP can be
      safely introduced as a new procedure without compromising patient outcomes.

PMID- 24917776
TI  - Novel use of the capio urethral anastomotic suturing device: a 50-case
      assessment.
AB  - OBJECTIVE: Robotic laparoscopic assisted prostatectomy (RALP) has become the
      predominant technique for prostatectomy despite significant expense and no robust
      evidence supporting better cancer control, erectile function, or continence.
      Several studies have demonstrated lower bladder neck contracture (BNC) rates with
      RALP, believed to be related to improved visualization and control of the
      urethrovesical anastomosis. We evaluated the CapioTM radical prostatectomy (RP)
      suture capturing device for improving anastomotic precision during urethrovesical
      anastomosis in open radical prostatectomy. MATERIALS AND METHODS: We performed a
      retrospective review on a single-surgeon series of 50 consecutive patients
      undergoing radical retropubic prostatectomy (RRP) with utilization of the CapioTM
      RP device at an academic hospital (February 2010 to May 2012). Patient
      demographics, pathology, and outcomes data including rates of anastomotic leak,
      BNC, erectile function, and continence were collected. RESULTS: Mean age of
      patients at the time of procedure was 60.4 +/- 6.43 years. Patients were
      stratifed by D'Amico criteria into low (14.3%), intermediate (67.4%), and high
      (18.4%) risk groups. Mean follow-up for all patients was 13.1 +/- 7.29 months. No
      patients were diagnosed with BNC within 90 days after surgery. Two patients (4%)
      were subsequently diagnosed and treated for BNC, one of whom was asymptomatic
      prior to diagnosis. CONCLUSION: Utilizing the CapioTM RP device during RRP, we
      were able to achieve a BNC rate equivalent to rates reported for RALP. Use of the
      CapioTM RP device appears to be a cost-effective method for improving RRP
      urethrovesical anastomotic results.

PMID- 24917777
TI  - Pubic bone osteomyelitis after salvage high-intensity focused ultrasound for
      prostate cancer.
AB  - High-intensity focused ultrasound can be used for the primary treatment of
      prostate cancer and biochemical recurrence after radical prostatectomy or
      radiation. Complications of high-intensity focused ultrasound include urinary
      retention, urethral stenosis, stress incontinence, urinary tract infections,
      dysuria, impotence, and rarely, rectourethral or rectovesicular fistula. We
      describe a patient presenting with urinary retention, urinary tract infections
      and intermittent stress incontinence, later found to be associated with pubic
      bone osteomyelitis stemming from a prostatopubic fistula. 

PMID- 24917778
TI  - Unusual urethral metastasis from colon carcinoma presenting with difficult
      urination and hematuria.
AB  - Urethral metastases originating from the colon are extremely rare. We report a
      case of a 67-year-old man who presented with difficult urination and hematuria.
      Diagnostic cystoscopy showed an abnormal, exophytic lesion in his proximal penile
      urethra a bulbar urethra. His pathology was diagnosed as adenocarcinoma
      consistent with colon metastasis. 

PMID- 24917779
TI  - Large cell neuroendocrine carcinoma of the urinary bladder: case report and
      review.
AB  - INTRODUCTION: Neuroendocrine carcinomas of the urinary bladder are relatively
      rare, accounting for less than 1% of all bladder carcinomas. These tumors can be
      divided into the more indolent typical or atypical carcinoid tumors and the
      aggressive small cell and large cell neuroendocrine carcinomas. OBJECTIVE: To
      report 2 clinical cases of large cell neuroendocrine carcinoma of the bladder
      (LCCB) and to review the epidemiology, prognosis, and current treatment
      algorithms for patients with bladder small and large cell neuroendocrine
      carcinomas. RESULTS: In both cases hematuria was the presenting symptom. One
      patient was submitted to partial cystectomy and the other to trans-urethral
      resection of the bladder tumor. The former patient died on the third month
      postoperatively. The latter patient had extensive liver metastasis at the time of
      diagnosis and died from acute liver failure on the 14th postoperative day. In
      review LCCB is associated with a more aggressive behavior and poorer prognosis
      than transitional cell bladder carcinoma. No standard approach exists. Surgery
      (transurethral ressection, partial cystectomy, radical cystectomy), chemotherapy
      and radiotherapy are current treatment modalities. CONCLUSION: LCCB is an
      aggressive tumor which usually presents itself in an advanced stage. Neoadjuvant
      chemotherapy with platinum regimen plus aggressive surgical approach should be
      the treatment of choice.

PMID- 24917780
TI  - Tibial metastasis from muscle invasive bladder carcinoma: an unusual site.
AB  - We report a case of a 61-year-old gentleman who presented with frank hematuria
      with associated weight loss and on-going left knee pain. Subsequent investigation
      revealed a muscle invasive bladder carcinoma with a related unusual bone
      metastasis. Though bone metastases form bladder carcinoma are common, frequent
      deposition sites include the spinal column and pelvis. This case report is to the
      best of our knowledge the first reported case of a tibial metastasis for relevant
      bladder carcinoma. Furthermore, we reviewed the literature, relevant diagnostic
      and management surrounding such occurrences. 

PMID- 24917781
TI  - Dural metastases in advanced prostate cancer: a case report and review of the
      literature.
AB  - Dural metastases from advanced prostate cancer are considered an uncommon
      diagnosis. However, autopsy studies show a high association between advanced
      prostate cancer and metastases to the meninges. Because the overall survival of
      advanced prostate cancer patients is expected to improve with the advent of new
      therapies, the incidence of clinically relevant dural metastases from prostate
      cancer will likely increase. We present a case of a heavily pre-treated
      castration-resistant prostate cancer patient who developed metastases to the
      duramater. This entity should be considered in the differential diagnosis of any
      patient with advanced castration-resistant prostate cancer and neurological
      symptoms. Clinicians should also be aware of the poor prognosis and survival
      rates associated with the condition. 

PMID- 24917782
TI  - Targeting central melanocortin receptors: a promising novel approach for treating
      alcohol abuse disorders.
AB  - The melanocortin (MC) peptides are produced centrally by propiomelanocortin
      (POMC) neurons within the arcuate nucleus of the hypothalamus and act through
      five seven-transmembrane G-protein coupled melanocortin receptor (MCR) subtypes.
      The MC3R and MC4R subtypes, the most abundant central MCRs, are widely expressed
      in brain regions known to modulate neurobiological responses to ethanol,
      including regions of the hypothalamus and extended amygdala. Agouti-related
      protein (AgRP), also produced in the arcuate nucleus, is secreted in terminals
      expressing MCRs and functions as an endogenous MCR antagonist. This review
      highlights recent genetic and pharmacological findings that have implicated roles
      for the MC and AgRP systems in modulating ethanol consumption. Ethanol
      consumption is associated with significant alterations in the expression levels
      of various MC peptides/protein, which suggests that ethanol-induced perturbations
      of MC/AgRP signaling may modulate excessive ethanol intake. Consistently, MCR
      agonists decrease, and AgRP increases, ethanol consumption in mice. MCR agonists
      fail to blunt ethanol intake in mutant mice lacking the MC4R, suggesting that the
      protective effects of MCR agonists are modulated by the MC4R. Interestingly,
      recent evidence reveals that MCR agonists are more effective at blunting binge
      like ethanol intake in mutant mice lacking the MC3R, suggesting that the MC3R has
      opposing effects on the MC4R. Finally, mutant mice lacking AgRP exhibit blunted
      voluntary and binge-like ethanol drinking, consistent with pharmacological
      studies. Collectively, these preclinical observations provide compelling evidence
      that compounds that target the MC system may provide therapeutic value for
      treating alcohol abuse disorders and that the utilization of currently available
      MC-targeting compounds- such as those being used to treat eating disorders- may
      be used as effective treatments to this end. 

PMID- 24917783
TI  - How learning to abstract shapes neural sound representations.
AB  - The transformation of acoustic signals into abstract perceptual representations
      is the essence of the efficient and goal-directed neural processing of sounds in
      complex natural environments. While the human and animal auditory system is
      perfectly equipped to process the spectrotemporal sound features, adequate sound
      identification and categorization require neural sound representations that are
      invariant to irrelevant stimulus parameters. Crucially, what is relevant and
      irrelevant is not necessarily intrinsic to the physical stimulus structure but
      needs to be learned over time, often through integration of information from
      other senses. This review discusses the main principles underlying categorical
      sound perception with a special focus on the role of learning and neural
      plasticity. We examine the role of different neural structures along the auditory
      processing pathway in the formation of abstract sound representations with
      respect to hierarchical as well as dynamic and distributed processing models.
      Whereas most fMRI studies on categorical sound processing employed speech sounds,
      the emphasis of the current review lies on the contribution of empirical studies
      using natural or artificial sounds that enable separating acoustic and perceptual
      processing levels and avoid interference with existing category representations.
      Finally, we discuss the opportunities of modern analyses techniques such as
      multivariate pattern analysis (MVPA) in studying categorical sound
      representations. With their increased sensitivity to distributed activation
      changes-even in absence of changes in overall signal level-these analyses
      techniques provide a promising tool to reveal the neural underpinnings of
      perceptually invariant sound representations. 

PMID- 24917784
TI  - Membrane guanylyl cyclase complexes shape the photoresponses of retinal rods and
      cones.
AB  - In vertebrate rods and cones, photon capture by rhodopsin leads to the
      destruction of cyclic GMP (cGMP) and the subsequent closure of cyclic nucleotide
      gated ion channels in the outer segment plasma membrane. Replenishment of cGMP
      and reopening of the channels limit the growth of the photon response and are
      requisite for its recovery. In different vertebrate retinas, there may be as many
      as four types of membrane guanylyl cyclases (GCs) for cGMP synthesis. Ten
      neuronal Ca(2+) sensor proteins could potentially modulate their activities. The
      mouse is proving to be an effective model for characterizing the roles of
      individual components because its relative simplicity can be reduced further by
      genetic engineering. There are two types of GC activating proteins (GCAPs) and
      two types of GCs in mouse rods, whereas cones express one type of GCAP and one
      type of GC. Mutant mouse rods and cones bereft of both GCAPs have large, long
      lasting photon responses. Thus, GCAPs normally mediate negative feedback tied to
      the light-induced decline in intracellular Ca(2+) that accelerates GC activity to
      curtail the growth and duration of the photon response. Rods from other mutant
      mice that express a single GCAP type reveal how the two GCAPs normally work
      together as a team. Because of its lower Ca(2+) affinity, GCAP1 is the first
      responder that senses the initial decrease in Ca(2+) following photon absorption
      and acts to limit response amplitude. GCAP2, with a higher Ca(2+) affinity, is
      recruited later during the course of the photon response as Ca(2+) levels
      continue to decline further. The main role of GCAP2 is to provide for a timely
      response recovery and it is particularly important after exposure to very bright
      light. The multiplicity of GC isozymes and GCAP homologs in the retinas of other
      vertebrates confers greater flexibility in shaping the photon responses in order
      to tune visual sensitivity, dynamic range and frequency response. 

PMID- 24917785
TI  - Systemic gene delivery to the central nervous system using Adeno-associated
      virus.
AB  - Adeno-associated virus (AAV)-mediated gene delivery has emerged as an effective
      and safe tool for both preclinical and clinical studies of neurological
      disorders. The recent discovery that several serotypes are able to cross the
      blood-brain barrier when administered systemically has been a real breakthrough
      in the field of neurodegenerative diseases. Widespread transgene expression after
      systemic injection could spark interest as a therapeutic approach. Such strategy
      will avoid invasive brain surgery and allow non-focal gene therapy promising for
      CNS diseases affecting large portion of the brain. Here, we will review the
      recent results achieved through different systemic routes of injection generated
      in the last decade using systemic AAV-mediated delivery and propose a brief
      assessment of their values. In particular, we emphasize how the methods used for
      virus engineering could improve brain transduction after peripheral delivery. 

PMID- 24917786
TI  - In silico, in vitro and cellular analysis with a kinome-wide inhibitor panel
      correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a complex, multidomain protein which is
      considered a valuable target for potential disease-modifying therapeutic
      strategies for Parkinson's disease (PD). In mammalian cells and brain, LRRK2 is
      phosphorylated and treatment of cells with inhibitors of LRRK2 kinase activity
      can induce LRRK2 dephosphorylation at a cluster of serines including
      Ser910/935/955/973. It has been suggested that phosphorylation levels at these
      sites reflect LRRK2 kinase activity, however kinase-dead variants of LRRK2 or
      kinase activating variants do not display altered Ser935 phosphorylation levels
      compared to wild type. Furthermore, Ser910/935/955/973 are not
      autophosphorylation sites, therefore, it is unclear if inhibitor induced
      dephosphorylation depends on the activity of compounds on LRRK2 or on yet to be
      identified upstream kinases. Here we used a panel of 160 ATP competitive and cell
      permeable kinase inhibitors directed against all branches of the kinome and
      tested their activity on LRRK2 in vitro using a peptide-substrate-based kinase
      assay. In neuronal SH-SY5Y cells overexpressing LRRK2 we used compound-induced
      dephosphorylation of Ser935 as readout. In silico docking of selected compounds
      was performed using a modeled LRRK2 kinase structure. Receiver operating
      characteristic plots demonstrated that the obtained docking scores to the LRRK2
      ATP binding site correlated with in vitro and cellular compound activity. We also
      found that in vitro potency showed a high degree of correlation to cellular
      compound induced LRRK2 dephosphorylation activity across multiple compound
      classes. Therefore, acute LRRK2 dephosphorylation at Ser935 in inhibitor treated
      cells involves a strong component of inhibitor activity on LRRK2 itself, without
      excluding a role for upstream kinases. Understanding the regulation of LRRK2
      phosphorylation by kinase inhibitors aids our understanding of LRRK2 signaling
      and may lead to development of new classes of LRRK2 kinase inhibitors. 

PMID- 24917787
TI  - Allopregnanolone and neuroinflammation: a focus on multiple sclerosis.
AB  - The progesterone derivative allopregnanolone (ALLO) is one of the most widely
      studied compounds among neurosteroids. Through interactions with GABA-A receptors
      expressed by neurons and glial cells, ALLO has been shown to affect diverse
      aspects of neural cell physiology, including cell proliferation and survival,
      migration, and gene expression. Recent data point to important roles for ALLO in
      different neurodegenerative disorders, including Alzheimer's disease, Parkinson's
      disease, and multiple sclerosis (MS). Dysregulation in ALLO biosynthesis pathways
      has been reported in brain tissue from MS patients as well as in the central
      nervous system (CNS) tissue derived from MS animal models. Administration of ALLO
      has been shown to ameliorate neurobehavioral deficits together with
      neuropathology and inflammation in the CNS of animals with autoimmune
      demyelination. These findings are in line with previous reports indicating growth
      and differentiation-promoting actions of ALLO on neurons and glial cells as well
      as its neuroprotective effects in the context of other CNS diseases. Nonetheless,
      these findings have also raised the possibility that ALLO might influence
      leukocyte biology and associated neuroinflammatory mechanisms independent of its
      neuroregenerative properties. Herein, we review the current knowledge regarding
      the role of ALLO in the pathogenesis of MS, and discuss the potential cellular
      and molecular pathways that might be influenced by ALLO in the context of
      disease. 

PMID- 24917788
TI  - Patch-clamp recordings of rat neurons from acute brain slices of the
      somatosensory cortex during magnetic stimulation.
AB  - Although transcranial magnetic stimulation (TMS) is a popular tool for both basic
      research and clinical applications, its actions on nerve cells are only partially
      understood. We have previously predicted, using compartmental modeling, that
      magnetic stimulation of central nervous system neurons depolarized the soma
      followed by initiation of an action potential in the initial segment of the axon.
      The simulations also predict that neurons with low current threshold are more
      susceptible to magnetic stimulation. Here we tested these theoretical predictions
      by combining in vitro patch-clamp recordings from rat brain slices with magnetic
      stimulation and compartmental modeling. In agreement with the modeling, our
      recordings demonstrate the dependence of magnetic stimulation-triggered action
      potentials on the type and state of the neuron and its orientation within the
      magnetic field. Our results suggest that the observed effects of TMS are deeply
      rooted in the biophysical properties of single neurons in the central nervous
      system and provide a framework both for interpreting existing TMS data and
      developing new simulation-based tools and therapies. 

PMID- 24917790
TI  - Activation of microglia bolsters synapse formation.

PMID- 24917789
TI  - Microglia change from a reactive to an age-like phenotype with the time in
      culture.
AB  - Age-related neurodegenerative diseases have been associated with chronic
      neuroinflammation and microglia activation. However, cumulative evidence supports
      that inflammation only occurs at an early stage once microglia change the
      endogenous characteristics with aging and switch to irresponsive/senescent and
      dystrophic phenotypes with disease progression. Thus, it will be important to
      have the means to assess the role of reactive and aged microglia when studying
      advanced brain neurodegeneration processes and age-associated related disorders.
      Yet, most studies are done with microglia from neonates since there are no
      adequate means to isolate degenerating microglia for experimentation. Indeed,
      only a few studies report microglia isolation from aged animals, using either
      short-term cultures or high concentrations of mitogens in the medium, which
      trigger microglia reactivity. The purpose of this study was to develop an
      experimental process to naturally age microglia after isolation from neonatal
      mice and to characterize the cultured cells at 2 days in vitro (DIV), 10 DIV, and
      16 DIV. We found that 2 DIV (young) microglia had predominant amoeboid morphology
      and markers of stressed/reactive phenotype. In contrast, 16 DIV (aged) microglia
      evidenced ramified morphology and increased matrix metalloproteinase (MMP)-2
      activation, as well as reduced MMP-9, glutamate release and nuclear factor kappa
      B activation, in parallel with decreased expression of Toll-like receptor (TLR)-2
      and TLR-4, capacity to migrate and phagocytose. These findings together with the
      reduced expression of microRNA (miR)-124, and miR-155, decreased autophagy,
      enhanced senescence associated beta-galactosidase activity and elevated miR-146a
      expression, are suggestive that 16 DIV cells mainly correspond to
      irresponsive/senescent microglia. Data indicate that the model represent an
      opportunity to understand and control microglial aging, as well as to explore
      strategies to recover microglia surveillance function. 

PMID- 24917791
TI  - Acute modulation of synaptic plasticity of pyramidal neurons by activin in adult
      hippocampus.
AB  - Activin A is known as a neuroprotective factor produced upon acute excitotoxic
      injury of the hippocampus (in pathological states). We attempt to reveal the role
      of activin as a neuromodulator in the adult male hippocampus under physiological
      conditions (in healthy states), which remains largely unknown. We showed
      endogenous/basal expression of activin in the hippocampal neurons. Localization
      of activin receptors in dendritic spines (=postsynapses) was demonstrated by
      immunoelectron microscopy. The incubation of hippocampal acute slices with
      activin A (10 ng/mL, 0.4 nM) for 2 h altered the density and morphology of spines
      in CA1 pyramidal neurons. The total spine density increased by 1.2-fold upon
      activin treatments. Activin selectively increased the density of large-head
      spines, without affecting middle-head and small-head spines. Blocking Erk/MAPK,
      PKA, or PKC prevented the activin-induced spinogenesis by reducing the density of
      large-head spines, independent of Smad-induced gene transcription which usually
      takes more than several hours. Incubation of acute slices with activin for 2 h
      induced the moderate early long-term potentiation (moderate LTP) upon weak theta
      burst stimuli. This moderate LTP induction was blocked by follistatin, MAPK
      inhibitor (PD98059) and inhibitor of NR2B subunit of NMDA receptors (Ro25-6981).
      It should be noted that the weak theta burst stimuli alone cannot induce moderate
      LTP. These results suggest that MAPK-induced phosphorylation of NMDA receptors
      (including NR2B) may play an important role for activin-induced moderate LTP.
      Taken together, the current results reveal interesting physiological roles of
      endogenous activin as a rapid synaptic modulator in the adult hippocampus. 

PMID- 24917794
TI  - Naps in school can enhance the duration of declarative memories learned by
      adolescents.
AB  - Sleep helps the consolidation of declarative memories in the laboratory, but the
      pro-mnemonic effect of daytime naps in schools is yet to be fully characterized.
      While a few studies indicate that sleep can indeed benefit school learning, it
      remains unclear how best to use it. Here we set out to evaluate the influence of
      daytime naps on the duration of declarative memories learned in school by
      students of 10-15 years old. A total of 584 students from 6th grade were
      investigated. Students within a regular classroom were exposed to a 15-min
      lecture on new declarative contents, absent from the standard curriculum for this
      age group. The students were then randomly sorted into nap and non-nap groups.
      Students in the nap group were conducted to a quiet room with mats, received
      sleep masks and were invited to sleep. At the same time, students in the non-nap
      group attended regular school classes given by their usual teacher (Experiment
      I), or English classes given by another experimenter (Experiment II). These 2
      versions of the study differed in a number of ways. In Experiment I (n = 371),
      students were pre-tested on lecture-related contents before the lecture, were
      invited to nap for up to 2 h, and after 1, 2, or 5 days received surprise tests
      with similar content but different wording and question order. In Experiment II
      (n = 213), students were invited to nap for up to 50 min (duration of a regular
      class); surprise tests were applied immediately after the lecture, and repeated
      after 5, 30, or 110 days. Experiment I showed a significant ~10% gain in test
      scores for both nap and non-nap groups 1 day after learning, in comparison with
      pre-test scores. This gain was sustained in the nap group after 2 and 5 days, but
      in the non-nap group it decayed completely after 5 days. In Experiment II, the
      nap group showed significantly higher scores than the non-nap group at all times
      tested, thus precluding specific conclusions. The results suggest that sleep can
      be used to enhance the duration of memory contents learned in school. 

PMID- 24917792
TI  - Trajectory of the main GABAergic interneuron populations from early development
      to old age in the rat primary auditory cortex.
AB  - In both humans and rodents, decline in cognitive function is a hallmark of the
      aging process; the basis for this decrease has yet to be fully characterized.
      However, using aged rodent models, deficits in auditory processing have been
      associated with significant decreases in inhibitory signaling attributed to a
      loss of GABAergic interneurons. Not only are these interneurons crucial for
      pattern detection and other large-scale population dynamics, but they have also
      been linked to mechanisms mediating plasticity and learning, making them a prime
      candidate for study and modeling of modifications to cortical communication
      pathways in neurodegenerative diseases. Using the rat primary auditory cortex
      (A1) as a model, we probed the known markers of GABAergic interneurons with
      immunohistological methods, using antibodies against gamma aminobutyric acid
      (GABA), parvalbumin (PV), somatostatin (SOM), calretinin (CR), vasoactive
      intestinal peptide (VIP), choline acetyltransferase (ChAT), neuropeptide Y (NPY),
      and cholecystokinin (CCK) to document the changes observed in interneuron
      populations across the rat's lifespan. This analysis provided strong evidence
      that several but not all GABAergic neurons were affected by the aging process,
      showing most dramatic changes in expression of parvalbumin (PV) and somatostatin
      (SOM) expression. With this evidence, we show how understanding these
      trajectories of cell counts may be factored into a simple model to quantify
      changes in inhibitory signaling across the course of life, which may be applied
      as a framework for creating more advanced simulations of interneuronal
      implication in normal cerebral processing, normal aging, or pathological
      processes. 

PMID- 24917793
TI  - Dynamic expression of calretinin in embryonic and early fetal human cortex.
AB  - Calretinin (CR) is one of the earliest neurochemical markers in human
      corticogenesis. In embryos from Carnegie stages (CS) 17 to 23, calbindin (CB) and
      CR stain opposite poles of the incipient cortex suggesting early regionalization:
      CB marks the neuroepithelium of the medial boundary of the cortex with the
      choroid plexus (cortical hem). By contrast, CR is confined to the subventricular
      zone (SVZ) of the lateral and caudal ganglionic eminences at the pallial
      subpallial boundary (PSB, or antihem), from where CR+/Tbr1- neurons migrate
      toward piriform cortex and amygdala as a component of the lateral cortical
      stream. At CS 19, columns of CR+ cells arise in the rostral cortex, and
      contribute at CS 20 to the "monolayer" of horizontal Tbr1+/CR+ and GAD+ cells in
      the preplate. At CS 21, the "pioneer cortical plate" appears as a radial
      aggregation of CR+/Tbr1+ neurons, which cover the entire future neocortex and
      extend the first corticofugal axons. CR expression in early human corticogenesis
      is thus not restricted to interneurons, but is also present in the first
      excitatory projection neurons of the cortex. At CS 21/22, the cortical plate is
      established following a lateral to medial gradient, when Tbr1+/CR- neurons settle
      within the pioneer cortical plate, and thus separate superficial and deep pioneer
      neurons. CR+ pioneer neurons disappear shortly after the formation of the
      cortical plate. Reelin+ Cajal-Retzius cells begin to express CR around CS21 (7/8
      PCW). At CS 21-23, the CR+ SVZ at the PSB is the source of CR+ interneurons
      migrating into the cortical SVZ. In turn, CB+ interneurons migrate from the
      subpallium into the intermediate zone following the fibers of the internal
      capsule. Early CR+ and CB+ interneurons thus have different origins and migratory
      routes. CR+ cell populations in the embryonic telencephalon take part in a
      complex sequence of events not analyzed so far in other mammalian species, which
      may represent a distinctive trait of the initial steps of human corticogenesis. 

PMID- 24917795
TI  - The relationship between vestibular function and topographical memory in older
      adults.
AB  - Research during the past two decades has demonstrated an important role of the
      vestibular system in topographical orientation and memory and the network of
      neural structures associated with them. Almost all of the supporting data have
      come from animal or human clinical studies, however. The purpose of the present
      study was to investigate the link between vestibular function and topographical
      memory in normal elderly humans. Twenty-five participants aged 70 to 85 years who
      scored from mildly impaired to normal on the Montreal Cognitive Assessment (MoCA)
      received three topographical memory tests: the Camden Topographical Recognition
      Memory Test (CTMRT), a computerized topographical mental rotation test (TMRT),
      and a virtual pond maze (VPM). They also received six vestibular or oculomotor
      tests: optokinetic nystagmus (OKN), visual pursuit (VP), actively generated
      vestibulo-ocular reflex (VOR), the sensory orientation test (SOT) for posture,
      and two measures of rotational memory (error in degrees, or RM degrees , and
      correct directional recognition, or RM->). The only significant bivariate
      correlations were among the three vestibular measures primarily assessing
      horizontal canal function (VOR, RM degrees , and RM->). A multiple regression
      analysis showed significant relationships between vestibular and demographic
      predictors and both the TMRT (R = 0.78) and VPM (R = 0.66) measures. The
      significant relationship between the vestibular and topographical memory measures
      supports the theory that vestibular loss may contribute to topographical memory
      impairment in the elderly. 

PMID- 24917796
TI  - Towards a concept of disorders of "higher vestibular function".
AB  - BACKGROUND: Vestibular disorders are commonly characterized by a combination of
      perceptual, ocular motor, postural, and vegetative manifestations, which cause
      the symptoms of vertigo, nystagmus, ataxia, and nausea. Multisensory convergence
      and numerous polysynaptic pathways link the bilaterally organized central
      vestibular network with limbic, hippocampal, cerebellar, and non-vestibular
      cortex structures to mediate "higher" cognitive functions. Anatomical
      classification of vestibular disorders: The traditional classification of
      vestibular disorders is based on the anatomical site of the lesion. While it
      distinguishes between the peripheral and the central vestibular systems, certain
      weaknesses become apparent when applied clinically. There are two reasons for
      this: first, peripheral and central vestibular disorders cannot always be
      separated by the clinical syndrome; second, a third category, namely disorders of
      "higher vestibular function", is missing. These disorders may be caused by
      peripheral as well as central vestibular lesions. Functional classification: Here
      we discuss a new concept of disorders of higher vestibular function which involve
      cognition and more than one sensory modality. Three conditions are described that
      exemplify such higher disorders: room tilt illusion, spatial hemineglect, and
      bilateral vestibulopathy all of which present with deficits of orientation and
      spatial memory. CONCLUSIONS: Further elaboration of such disorders of higher
      multisensory functions with respect to lesion site and symptomatology is
      desirable. The room tilt illusion and spatial hemineglect involve vestibular and
      visual function to the extent that both conditions can be classified as either
      disorders of higher vestibular or of higher visual functions. A possible way of
      separating these disorders in a first step is to determine whether the causative
      lesion site affects the vestibular or the visual system. For the vestibular
      system this lesion site may be peripheral or central. The criterion of "higher
      function" is fulfilled if cognition or senses other than the primarily affected
      one come into play.

PMID- 24917797
TI  - Change in hippocampal theta activity with transfer from simple discrimination
      tasks to a simultaneous feature-negative task.
AB  - It was showed that solving a simple discrimination task (A+, B-) and a
      simultaneous feature-negative (FN) task (A+, AB-) used the hippocampal
      independent strategy. Recently, we showed that the number of sessions required
      for a rat to completely learn a task differed between the FN and simple
      discrimination tasks, and there was a difference in hippocampal theta activity
      between these tasks. These results suggested that solving the FN task relied on a
      different strategy than the simple discrimination task. In this study, we
      provided supportive evidence that solving the FN and simple discrimination tasks
      involved different strategies by examining changes in performance and hippocampal
      theta activity in the FN task after transfer from the simple discrimination task
      (A+, B- -> A+, AB-). The results of this study showed that performance on the FN
      task was impaired and there was a difference in hippocampal theta activity
      between the simple discrimination task and FN task. Thus, we concluded that
      solving the FN task uses a different strategy than the simple discrimination
      task. 

PMID- 24917798
TI  - Dissociating retrieval success from incidental encoding activity during emotional
      memory retrieval, in the medial temporal lobe.
AB  - The memory-enhancing effect of emotion has been linked to the engagement of
      emotion- and memory-related medial temporal lobe (MTL) regions (amygdala-AMY;
      hippocampus-HC; parahippocampus-PHC), during both encoding and retrieval.
      However, recognition tasks used to investigate the neural correlates of retrieval
      make it difficult to distinguish MTL engagement linked to retrieval success (RS)
      from that linked to incidental encoding success (ES) during retrieval. This issue
      has been investigated for retrieval of non-emotional memories, but not for
      emotional memory retrieval. To address this, we used event-related functional MRI
      in conjunction with an emotional distraction and two episodic memory tasks (one
      testing memory for distracter items and the other testing memory for new/lure
      items presented in the first memory task). This paradigm allowed for dissociation
      of MTL activity specifically linked to RS from that linked to both RS and
      incidental ES during retrieval. There were two novel findings regarding the
      neural correlates of emotional memory retrieval. First, greater emotional RS was
      identified bilaterally in AMY, HC, and PHC. However, AMY activity was most
      impacted when accounting for ES activity, as only RS activity in left AMY was
      dissociated from ES activity during retrieval, whereas portions of HC and PHC
      showing greater emotional RS were largely uninvolved in ES. Second, an earlier
      and more anteriorly spread response (left AMY and bilateral HC, PHC) was linked
      to greater emotional RS activity, whereas a later and more posteriorly localized
      response (right posterior PHC) was linked to greater neutral RS activity. These
      findings shed light on MTL mechanisms subserving the memory-enhancing effect of
      emotion at retrieval. 

PMID- 24917799
TI  - How does the modular organization of entorhinal grid cells develop?
AB  - The entorhinal-hippocampal system plays a crucial role in spatial cognition and
      navigation. Since the discovery of grid cells in layer II of medial entorhinal
      cortex (MEC), several types of models have been proposed to explain their
      development and operation; namely, continuous attractor network models,
      oscillatory interference models, and self-organizing map (SOM) models. Recent
      experiments revealing the in vivo intracellular signatures of grid cells
      (Domnisoru et al., 2013; Schmidt-Heiber and Hausser, 2013), the primarily
      inhibitory recurrent connectivity of grid cells (Couey et al., 2013; Pastoll et
      al., 2013), and the topographic organization of grid cells within anatomically
      overlapping modules of multiple spatial scales along the dorsoventral axis of MEC
      (Stensola et al., 2012) provide strong constraints and challenges to existing
      grid cell models. This article provides a computational explanation for how MEC
      cells can emerge through learning with grid cell properties in modular
      structures. Within this SOM model, grid cells with different rates of temporal
      integration learn modular properties with different spatial scales. Model grid
      cells learn in response to inputs from multiple scales of directionally-selective
      stripe cells (Krupic et al., 2012; Mhatre et al., 2012) that perform path
      integration of the linear velocities that are experienced during navigation.
      Slower rates of grid cell temporal integration support learned associations with
      stripe cells of larger scales. The explanatory and predictive capabilities of the
      three types of grid cell models are comparatively analyzed in light of recent
      data to illustrate how the SOM model overcomes problems that other types of
      models have not yet handled. 

PMID- 24917800
TI  - Brain connectivity in autism.

PMID- 24917801
TI  - A similar correction mechanism in slow and fluent readers after suboptimal
      landing positions.
AB  - The present eye movements study investigated the optimal viewing position (OVP)
      and inverted-optimal viewing position (I-OVP) effects in slow readers. The basis
      of these effects is a phenomenon called corrective re-fixations, which describes
      a short saccade from a suboptimal landing position (word beginning or end) to the
      center of the word. The present study found corrective re-fixations in slow
      readers, which was evident from the I-OVP effects in first fixation durations,
      the OVP effect in number of fixations and the OVP effect in re-fixation
      probability. The main result is that slow readers, despite being characterized by
      a fragmented eye movement pattern during reading, nevertheless share an intact
      mechanism for performing corrective re-fixations. This correction mechanism is
      not linked to linguistic processing, but to visual and oculomotor processes,
      which suggests the integrity of oculomotor and visual processes in slow readers. 

PMID- 24917802
TI  - The locus of impairment in English developmental letter position dyslexia.
AB  - Many children with reading difficulties display phonological deficits and
      struggle to acquire non-lexical reading skills. However, not all children with
      reading difficulties have these problems, such as children with selective letter
      position dyslexia (LPD), who make excessive migration errors (such as reading
      slime as "smile"). Previous research has explored three possible loci for the
      deficit - the phonological output buffer, the orthographic input lexicon, and the
      orthographic-visual analysis stage of reading. While there is compelling evidence
      against a phonological output buffer and orthographic input lexicon deficit
      account of English LPD, the evidence in support of an orthographic-visual
      analysis deficit is currently limited. In this multiple single-case study with
      three English-speaking children with developmental LPD, we aimed to both
      replicate and extend previous findings regarding the locus of impairment in
      English LPD. First, we ruled out a phonological output buffer and an orthographic
      input lexicon deficit by administering tasks that directly assess phonological
      processing and lexical guessing. We then went on to directly assess whether or
      not children with LPD have an orthographic-visual analysis deficit by modifying
      two tasks that have previously been used to localize processing at this level: a
      same-different decision task and a non-word reading task. The results from these
      tasks indicate that LPD is most likely caused by a deficit specific to the coding
      of letter positions at the orthographic-visual analysis stage of reading. These
      findings provide further evidence for the heterogeneity of dyslexia and its
      underlying causes. 

PMID- 24917803
TI  - Hand specific representations in language comprehension.
AB  - Theories of embodied cognition argue that language comprehension involves sensory
      motor re-enactments of the actions described. However, the degree of specificity
      of these re-enactments as well as the relationship between action and language
      remains a matter of debate. Here we investigate these issues by examining how
      hand-specific information (left or right hand) is recruited in language
      comprehension and action execution. An fMRI study tested self-reported right
      handed participants in two separate tasks that were designed to be as similar as
      possible to increase sensitivity of the comparison across task: an action
      execution go/no-go task where participants performed right or left hand actions,
      and a language task where participants read sentences describing the same left or
      right handed actions as in the execution task. We found that language-induced
      activity did not match the hand-specific patterns of activity found for action
      execution in primary somatosensory and motor cortex, but it overlapped with pre
      motor and parietal regions associated with action planning. Within these pre
      motor regions, both right hand actions and sentences elicited stronger activity
      than left hand actions and sentences-a dominant hand effect. Importantly, both
      dorsal and ventral sections of the left pre-central gyrus were recruited by both
      tasks, suggesting different action features being recruited. These results
      suggest that (a) language comprehension elicits motor representations that are
      hand-specific and akin to multimodal action plans, rather than full action re
      enactments; and (b) language comprehension and action execution share schematic
      hand-specific representations that are richer for the dominant hand, and thus
      linked to previous motor experience. 

PMID- 24917804
TI  - Pervasive brain monitoring and data sharing based on multi-tier distributed
      computing and linked data technology.
AB  - EEG-based Brain-computer interfaces (BCI) are facing basic challenges in real
      world applications. The technical difficulties in developing truly wearable BCI
      systems that are capable of making reliable real-time prediction of users'
      cognitive states in dynamic real-life situations may seem almost insurmountable
      at times. Fortunately, recent advances in miniature sensors, wireless
      communication and distributed computing technologies offered promising ways to
      bridge these chasms. In this paper, we report an attempt to develop a pervasive
      on-line EEG-BCI system using state-of-art technologies including multi-tier Fog
      and Cloud Computing, semantic Linked Data search, and adaptive
      prediction/classification models. To verify our approach, we implement a pilot
      system by employing wireless dry-electrode EEG headsets and MEMS motion sensors
      as the front-end devices, Android mobile phones as the personal user interfaces,
      compact personal computers as the near-end Fog Servers and the computer clusters
      hosted by the Taiwan National Center for High-performance Computing (NCHC) as the
      far-end Cloud Servers. We succeeded in conducting synchronous multi-modal global
      data streaming in March and then running a multi-player on-line EEG-BCI game in
      September, 2013. We are currently working with the ARL Translational Neuroscience
      Branch to use our system in real-life personal stress monitoring and the UCSD
      Movement Disorder Center to conduct in-home Parkinson's disease patient
      monitoring experiments. We shall proceed to develop the necessary BCI ontology
      and introduce automatic semantic annotation and progressive model refinement
      capability to our system. 

PMID- 24917805
TI  - Saccade-vergence properties remain more stable over short-time repetition under
      overlap than under gap task: a preliminary study.
AB  - Under natural circumstances, saccade-vergence eye movements are among the most
      frequently occurring. This study examines the properties of such movements
      focusing on short-term repetition effects. Are such movements robust over time or
      are they subject to tiredness? 12 healthy adults performed convergent and
      divergent combined eye movements either in a gap task (i.e., 200 ms between the
      end of the fixation stimulus and the beginning of the target stimulus) or in an
      overlap task (i.e., the peripheral target begins 200 ms before the end of the
      fixation stimulus). Latencies were shorter in the gap task than in the overlap
      task for both saccade and vergence components. Repetition had no effect on
      latency, which is a novel result. In both tasks, saccades were initiated later
      and executed faster (mean and peak velocities) than the vergence component. The
      mean and peak velocities of both components decreased over trials in the gap task
      but remained constant in the overlap task. This result is also novel and has some
      clinical implications. Another novel result concerns the accuracy of the saccade
      component that was better in the gap than in the overlap task. The accuracy also
      decreased over trials in the gap task but remained constant in the overlap task.
      The major result of this study is that under a controlled mode of initiation
      (overlap task) properties of combined eye movements are more stable than under
      automatic triggering (gap task). These results are discussed in terms of saccade
      vergence interactions, convergence-divergence specificities and repetition versus
      adaptation protocols. 

PMID- 24917806
TI  - The neural underpinnings of vicarious experience.

PMID- 24917807
TI  - Creativity, brain, and art: biological and neurological considerations.
AB  - Creativity is commonly thought of as a positive advance for society that
      transcends the status quo knowledge. Humans display an inordinate capacity for it
      in a broad range of activities, with art being only one. Most work on
      creativity's neural substrates measures general creativity, and that is done with
      laboratory tasks, whereas specific creativity in art is gleaned from acquired
      brain damage, largely in observing established visual artists, and some in visual
      de novo artists (became artists after the damage). The verb "to create" has been
      erroneously equated with creativity; creativity, in the classic sense, does not
      appear to be enhanced following brain damage, regardless of etiology. The turning
      to communication through art in lieu of language deficits reflects a biological
      survival strategy. Creativity in art, and in other domains, is most likely
      dependent on intact and healthy knowledge and semantic conceptual systems, which
      are represented in several pathways in the cortex. It is adversely affected when
      these systems are dysfunctional, for congenital reasons (savant autism) or
      because of acquired brain damage (stroke, dementia, Parkinson's), whereas
      inherent artistic talent and skill appear less affected. Clues to the neural
      substrates of general creativity and specific art creativity can be gleaned from
      considering that art is produced spontaneously mainly by humans, that there are
      unique neuroanatomical and neurofunctional organizations in the human brain, and
      that there are biological antecedents of innovation in animals. 

PMID- 24917808
TI  - Enhancing aesthetic appreciation by priming canvases with actions that match the
      artist's painting style.
AB  - The creation of an artwork requires motor activity. To what extent is art
      appreciation divorced from that activity and to what extent is it linked to it?
      That is the question which we set out to answer. We presented participants with
      pointillist-style paintings featuring discernible brushstrokes and asked them to
      rate their liking of each canvas when it was preceded by images priming a motor
      act either compatible or incompatible with the simulation of the artist's
      movements. We show that action priming, when congruent with the artist's painting
      style, enhanced aesthetic preference. These results support the hypothesis that
      involuntary covert painting simulation contributes to aesthetic appreciation
      during passive observation of artwork. 

PMID- 24917809
TI  - Long-term memory: scaling of information to brain size.

PMID- 24917810
TI  - Induction of plasticity in the human motor cortex by pairing an auditory stimulus
      with TMS.
AB  - Acoustic stimuli can cause a transient increase in the excitability of the motor
      cortex. The current study leverages this phenomenon to develop a method for
      testing the integrity of auditorimotor integration and the capacity for
      auditorimotor plasticity. We demonstrate that appropriately timed transcranial
      magnetic stimulation (TMS) of the hand area, paired with auditorily mediated
      excitation of the motor cortex, induces an enhancement of motor cortex
      excitability that lasts beyond the time of stimulation. This result demonstrates
      for the first time that paired associative stimulation (PAS)-induced plasticity
      within the motor cortex is applicable with auditory stimuli. We propose that the
      method developed here might provide a useful tool for future studies that measure
      auditory-motor connectivity in communication disorders. 

PMID- 24917811
TI  - Neurobiological, cognitive, and emotional mechanisms in melodic intonation
      therapy.
AB  - Singing has been used in language rehabilitation for decades, yet controversy
      remains over its effectiveness and mechanisms of action. Melodic Intonation
      Therapy (MIT) is the most well-known singing-based therapy; however, speculation
      surrounds when and how it might improve outcomes in aphasia and other language
      disorders. While positive treatment effects have been variously attributed to
      different MIT components, including melody, rhythm, hand-tapping, and the choral
      nature of the singing, there is uncertainty about the components that are truly
      necessary and beneficial. Moreover, the mechanisms by which the components
      operate are not well understood. Within the literature to date, proposed
      mechanisms can be broadly grouped into four categories: (1) neuroplastic
      reorganization of language function, (2) activation of the mirror neuron system
      and multimodal integration, (3) utilization of shared or specific features of
      music and language, and (4) motivation and mood. In this paper, we review
      available evidence for each mechanism and propose that these mechanisms are not
      mutually exclusive, but rather represent different levels of explanation,
      reflecting the neurobiological, cognitive, and emotional effects of MIT. Thus,
      instead of competing, each of these mechanisms may contribute to language
      rehabilitation, with a better understanding of their relative roles and
      interactions allowing the design of protocols that maximize the effectiveness of
      singing therapy for aphasia. 

PMID- 24917812
TI  - Population coding in mouse visual cortex: response reliability and dissociability
      of stimulus tuning and noise correlation.
AB  - The primary visual cortex is an excellent model system for investigating how
      neuronal populations encode information, because of well-documented relationships
      between stimulus characteristics and neuronal activation patterns. We used two
      photon calcium imaging data to relate the performance of different methods for
      studying population coding (population vectors, template matching, and Bayesian
      decoding algorithms) to their underlying assumptions. We show that the
      variability of neuronal responses may hamper the decoding of population activity,
      and that a normalization to correct for this variability may be of critical
      importance for correct decoding of population activity. Second, by comparing
      noise correlations and stimulus tuning we find that these properties have
      dissociated anatomical correlates, even though noise correlations have been
      previously hypothesized to reflect common synaptic input. We hypothesize that
      noise correlations arise from large non-specific increases in spiking activity
      acting on many weak synapses simultaneously, while neuronal stimulus response
      properties are dependent on more reliable connections. Finally, this paper
      provides practical guidelines for further research on population coding and shows
      that population coding cannot be approximated by a simple summation of inputs,
      but is heavily influenced by factors such as input reliability and noise
      correlation structure. 

PMID- 24917813
TI  - Predictable internal brain dynamics in EEG and its relation to conscious states.
AB  - Consciousness is a complex and multi-faceted phenomenon defying scientific
      explanation. Part of the reason why this is the case is due to its subjective
      nature. In our previous computational experiments, to avoid such a subjective
      trap, we took a strategy to investigate objective necessary conditions of
      consciousness. Our basic hypothesis was that predictive internal dynamics serves
      as such a condition. This is in line with theories of consciousness that treat
      retention (memory), protention (anticipation), and primary impression as the
      tripartite temporal structure of consciousness. To test our hypothesis, we
      analyzed publicly available sleep and awake electroencephalogram (EEG) data. Our
      results show that EEG signals from awake or rapid eye movement (REM) sleep states
      have more predictable dynamics compared to those from slow-wave sleep (SWS).
      Since awakeness and REM sleep are associated with conscious states and SWS with
      unconscious or less consciousness states, these results support our hypothesis.
      The results suggest an intricate relationship among prediction, consciousness,
      and time, with potential applications to time perception and neurorobotics. 

PMID- 24917815
TI  - Increased risk of ischemic stroke in patients with benign paroxysmal positional
      vertigo: a 9-year follow-up nationwide population study in taiwan.
AB  - Benign paroxysmal positional vertigo (BPPV) is a common form of vertigo and is
      characterized by episodic dizziness related to changes in head position relative
      to gravity. BPPV symptoms can be similar to those of central nervous system
      vascular diseases. The association between BPPV and ischemic stroke has not yet
      been investigated. The study cohort consisted of patients who were diagnosed with
      BPPV at least twice in the previous year as an outpatient or for whom BPPV was
      the primary diagnosis as an inpatient (n = 4104). An age- and gender-matched
      sample that excluded patients with a diagnosis of any form of vertigo was
      selected as the comparison cohort (n = 8397). All cases were followed up from
      January 1, 2000, to December 31, 2008. The demographic characteristics, medical
      comorbidities, and use of medications in both groups were investigated using chi
      square tests. A stratified analysis of stroke risk factors was performed to
      determine the hazard ratios of BPPV. During the 9-year follow-up period, 185 of
      the 4104 (4.5%) subjects with BPPV and 240 of the 8379 (2.9%) subjects without
      BPPV developed ischemic strokes. The crude hazard ratio of BPPV for developing
      ischemic strokes was 1.708. After adjusting for stroke risk factors, the risk of
      developing ischemic strokes in BPPV subjects was 1.415-fold higher than the risk
      among those without BPPV (confidence interval: 1.162-1.732, p = 0.001). After a
      subgroup analysis stratified according to stroke risk factors, BPPV remained
      independently associated with a higher risk of developing future ischemic stroke.
      We conclude that BPPV is independently associated with a risk of subsequent
      ischemic stroke. More aggressive control of modifiable risk factors for ischemic
      strokes should be conducted in patients with BPPV. 

PMID- 24917814
TI  - SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating
      telomere shelterin.
AB  - Mesenchymal stem cells (MSCs) senescence is an age-related process that impairs
      the capacity for tissue repair and compromises the clinical use of autologous
      MSCs for tissue regeneration. Here, we describe the effects of SIRT1, a NAD(+)
      dependent deacetylase, on age-related MSCs senescence. Knockdown of SIRT1 in
      young MSCs induced cellular senescence and inhibited cell proliferation whereas
      overexpression of SIRT1 in aged MSCs reversed the senescence phenotype and
      stimulated cell proliferation. These results suggest that SIRT1 plays a key role
      in modulating age-induced MSCs senescence. Aging-related proteins, P16 and P21
      may be downstream effectors of the SIRT1-mediated anti-aging effects. SIRT1
      protected MSCs from age-related DNA damage, induced telomerase reverse
      transcriptase (TERT) expression and enhanced telomerase activity but did not
      affect telomere length. SIRT1 positively regulated the expression of tripeptidyl
      peptidase 1 (TPP1), a component of the shelterin pathway that protects chromosome
      ends from DNA damage. Together, the results demonstrate that SIRT1 quenches age
      related MSCs senescence by mechanisms that include enhanced TPP1 expression,
      increased telomerase activity and reduced DNA damage. 

PMID- 24917816
TI  - New pathobiochemical insights into dystrophinopathy from the proteomics of
      senescent mdx mouse muscle.
AB  - Primary abnormalities in the dystrophin gene cause X-linked muscular dystrophy, a
      highly progressive muscle wasting disorder of childhood. A spontaneous animal
      model of Duchenne muscular dystrophy is the mdx mouse, which presents a highly
      interesting phenotype that exhibits considerable variations in the degree of
      fiber degeneration in different subtypes of muscles. The idea that aging
      exacerbates the dystrophic mdx phenotype, as previously indicated by a large
      number of biochemical and cell biological studies, was clearly confirmed by
      comparative muscle proteomics. Here we outline recent findings of age-dependent
      changes in the dystrophin-deficient muscle proteome and contrast these results
      with the previously established proteomic profile of sarcopenic muscle. Besides
      comparable perturbations of various biochemical functions, especially striking
      are similarities in the cellular stress response associated with a drastic up
      regulation of small alphaB-crystallin-like heat shock proteins. Hence, the
      comparison of large-scale proteomic data sets of natural muscle aging with
      dystrophic sarcopenia promises to shed light on the differential effect of
      sarcopenia of old age vs. senescent abnormalities on a mutant dystrophic
      background. 

PMID- 24917817
TI  - Etanercept induces remission of polyarteritis nodosa: a case report.

PMID- 24917818
TI  - The role of perioperative sodium bicarbonate infusion affecting renal function
      after cardiothoracic surgery.
AB  - Cardiac surgery associated acute kidney injury (CSA-AKI) is associated with poor
      outcomes including increased mortality, length of hospital stay (LOS) and cost.
      The incidence of acute kidney injury (AKI) is reported to be between 3 and 30%
      depending on the definition of AKI. We designed a multicenter randomized
      controlled trial to test our hypothesis that a perioperative infusion of sodium
      bicarbonate (SB) during cardiac surgery will attenuate the post-operative rise in
      creatinine indicating renal injury when compared to a perioperative infusion with
      normal saline. An interim analysis was performed after data was available on the
      first 120 participants. A similar number of patients in the two treatment groups
      developed AKI, defined as an increase in serum creatinine the first 48 h after
      surgery of 0.3 mg/dl or more. Specifically 14 patients (24%) who received sodium
      chloride (SC) and 17 patients (27%) who received SB were observed to develop AKI
      post-surgery, resulting in a relative risk of AKI of 1.1 (95% CI: 0.6-2.1, chi
      square p-value = 0.68) for patients receiving SB compared to those who received
      SC. The data safety monitoring board for the trial recommended closing the study
      early as there was only a 12% probability that the null hypothesis would be
      rejected. We therefore concluded that a perioperative infusion of SB failed to
      attenuate the risk of CSA-AKI. 

PMID- 24917819
TI  - Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron
      sulfur cluster deficit to mitochondrial iron accumulation.
AB  - Friedreich ataxia (FRDA) is the most common recessive ataxia in the Caucasian
      population and is characterized by a mixed spinocerebellar and sensory ataxia
      frequently associating cardiomyopathy. The disease results from decreased
      expression of the FXN gene coding for the mitochondrial protein frataxin. Early
      histological and biochemical study of the pathophysiology in patient's samples
      revealed that dysregulation of iron metabolism is a key feature of the disease,
      mainly characterized by mitochondrial iron accumulation and by decreased activity
      of iron-sulfur cluster enzymes. In the recent past years, considerable progress
      in understanding the function of frataxin has been provided through cellular and
      biochemical approaches, pointing to the primary role of frataxin in iron-sulfur
      cluster biogenesis. However, why and how the impact of frataxin deficiency on
      this essential biosynthetic pathway leads to mitochondrial iron accumulation is
      still poorly understood. Herein, we review data on both the primary function of
      frataxin and the nature of the iron metabolism dysregulation in FRDA. To date,
      the pathophysiological implication of the mitochondrial iron overload in FRDA
      remains to be clarified. 

PMID- 24917820
TI  - Integrins and cadherins as therapeutic targets in fibrosis.
AB  - Fibrosis is the excessive deposition of extracellular matrix proteins into
      tissues leading to scar formation, disruption of normal tissue architecture and
      organ failure. Despite the large clinical impact of fibrosis, treatment options
      are limited. Adhesion molecules, in particular alphavbeta6 and alpha3beta1
      integrins and cadherin-11, have been demonstrated to be important mediators of
      tissue fibrosis. These data are reviewed here and provide the foundation for
      these molecules to be potential therapeutic targets for patients with fibrotic
      diseases. 

PMID- 24917821
TI  - Tumor suppression in skin and other tissues via cross-talk between vitamin D- and
      p53-signaling.
AB  - P53 and its family members have been implicated in the direct regulation of the
      vitamin D receptor (VDR). Vitamin D- and p53-signaling pathways have a
      significant impact on spontaneous or carcinogen-induced malignant transformation
      of cells, with VDR and p53 representing important tumor suppressors. VDR and the
      p53/p63/p73 proteins all function typically as receptors or sensors that turn
      into transcriptional regulators upon stimulus, with the main difference being
      that the nuclear VDR is activated as a transcription factor after binding its
      naturally occurring ligand 1,25-dihydroxyvitamin D with high affinity while the
      p53 family of transcription factors, mostly in the nucleoplasm, responds to a
      large number of alterations in cell homeostasis commonly referred to as stress.
      An increasing body of evidence now convincingly demonstrates a cross-talk between
      vitamin D- and p53-signaling that occurs at different levels, has genome-wide
      implications and that should be of high importance for many malignancies,
      including non-melanoma skin cancer. One interaction involves the ability of p53
      to increase skin pigmentation via POMC derivatives including alpha-MSH and ACTH.
      Pigmentation protects the skin against UV-induced DNA damage and skin
      carcinogenesis, yet on the other hand reduces cutaneous synthesis of vitamin D. A
      second level of interaction may be through the ability of 1,25-dihydroxyvitamin D
      to increase the survival of skin cells after UV irradiation. UV irradiation
      surviving cells show significant reductions in thymine dimers in the presence of
      1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein
      expression, and significantly reduced NO products. A third level of interaction
      is documented by the ability of vitamin D compounds to regulate the expression of
      the murine double minute 2 (MDM2) gene in dependence of the presence of wild-type
      p53. MDM2 has a well-established role as a key negative regulator of p53
      activity. Finally, p53 and family members have been implicated in the direct
      regulation of VDR. This overview summarizes some of the implications of the cross
      talk between vitamin D- and p53-signaling for carcinogenesis in the skin and
      other tissues. 

PMID- 24917822
TI  - The buffer capacity of airway epithelial secretions.
AB  - The pH of airway epithelial secretions influences bacterial killing and mucus
      properties and is reduced by acidic pollutants, gastric reflux, and respiratory
      diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on
      buffer capacity, however the buffering of airway secretions has not been well
      characterized. In this work we develop a method for titrating micro-scale (30
      MUl) volumes and use it to study fluid secreted by the human airway epithelial
      cell line Calu-3, a widely used model for submucosal gland serous cells.
      Microtitration curves revealed that HCO(-) 3 is the major buffer. Peak buffer
      capacity (beta) increased from 17 to 28 mM/pH during forskolin stimulation, and
      was reduced by >50% in fluid secreted by cystic fibrosis transmembrane
      conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important
      role of CFTR in HCO(-) 3 secretion. Back-titration with NaOH revealed non
      volatile buffer capacity due to proteins synthesized and released by the
      epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3
      fluid significantly, however model titrations of porcine gastric mucins at
      concentrations near the sol-gel transition suggest that mucins may contribute to
      the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO(-) 3
      secretion and epithelially-derived proteins are the predominant buffers in Calu-3
      secretions. 

PMID- 24917823
TI  - Effect of contraction intensity on sympathetic nerve activity to active human
      skeletal muscle.
AB  - The effect of contraction intensity on muscle sympathetic nerve activity (MSNA)
      to active human limbs has not been established. To address this, MSNA was
      recorded from the left peroneal nerve during and after dorsiflexion contractions
      sustained for 2 min by the left leg at ~10, 25, and 40% MVC. To explore the
      involvement of the muscle metaboreflex, limb ischemia was imposed midway during
      three additional contractions and maintained during recovery. Compared with total
      MSNA at rest (11.5 +/- 4.1 mv(.)min(-1)), MSNA in the active leg increased
      significantly at the low (21.9 +/- 13.6 mv(.)min(-1)), medium (30.5 +/- 20.8
      mv(.)min(-1)), and high (50.0 +/- 24.5 mv(.)min(-1)) intensities. This intensity
      dependent effect was more strongly associated with increases in MSNA burst
      amplitude than burst frequency. Total MSNA then returned to resting levels within
      the first minute of recovery. Limb ischemia had no significant influence on the
      intensity-dependent rise in MSNA or its decline during recovery in the active
      leg. These findings reveal intensity-dependent increases in total MSNA and burst
      amplitude to contracting human skeletal muscle that do not appear to involve the
      muscle metaboreflex. 

PMID- 24917824
TI  - The effect of a peer on VO2 and game choice in 6-10 year old children.
AB  - Relative to sedentary video games (e.g., Playstation 2(r)), playing physically
      active video games (e.g., Nintendo Wii Sports Boxing(r)) significantly increases
      caloric expenditure in children. Studies have demonstrated that the presence of a
      peer increases physical activity in children. We sought to determine if children
      would expend more energy and find playing the "exergame" (Wii) more motivating
      than the sedentary video game (Playstation 2) when with a peer. Seventeen
      children (age 8.5 +/- 0.4 years) rested, played the sedentary video game and
      "exergame" for 10 min each, in two conditions: one in which the children
      rested/played the games alone (alone condition) and another in which they played
      with a peer (peer condition). Oxygen consumption (VO2), and liking (visual analog
      scale) was assessed for each 10-min condition. After three 10-min resting/gaming
      conditions, motivation was assessed using a relative reinforcing value task in
      which children performed computer mouse presses to gain additional access for
      either the sedentary video game or "exergame." VO2 was greater (p < 0.001) during
      "exergame" play (mean = 12.17 +/- 4.1 ml.kg(-1).min(-1)) vs. rest (mean = 5.14 +/
      1.46 ml.kg(-1).min(-1)) and the sedentary video game (mean = 5.83 +/- 2.1 ml.kg(
      1).min(-1)). During the peer condition, there were no significant differences (p
      > 0.05) in VO2 relative to the alone condition. In an exploratory analysis boys
      exhibited a greater (p = 0.02) increase in VO2 from rest to "exergame" (Delta 9.0
      +/- 3.7 ml.kg(-1).min(-1)), relative to girls (Delta 4.9 +/- 2.9 ml.kg(-1).min(
      1)). Boys showed a significantly greater increase (p = 0.05) in VO2 from the
      resting condition to "exergame" in the presence of a peer (Delta 11.1 +/- 5.3
      ml.kg(-1).min(-1)) vs. the alone condition (Delta 6.8 +/- 3.1 ml.kg(-1) .min(
      1)). Liking was significantly (p < 0.001) greater for "exergame" (7.7 +/- 1.9 cm)
      and the sedentary video game (8.3 +/- 1.3 cm) relative to rest (4.0 +/- 2.8 cm).
      Motivation for "exergame" significantly decreased (p = 0.03) from alone (340.8 +/
      106.8 presses) to the peer condition (147.8 +/- 81.6 presses). CONCLUSION: VO2
      was greater during "exergame" play relative to the sedentary video game. The
      presence of a peer did not increase VO2 during "exergame" play. Surprisingly, the
      presence of a peer decreased children's motivation to play "exergame" vs. the
      sedentary video game.

PMID- 24917825
TI  - Effect of heart rate correction on pre- and post-exercise heart rate variability
      to predict risk of mortality-an experimental study on the FINCAVAS cohort.
AB  - The non-linear inverse relationship between RR-intervals and heart rate (HR)
      contributes significantly to the heart rate variability (HRV) parameters and
      their performance in mortality prediction. To determine the level of influence HR
      exerts over HRV parameters' prognostic power, we studied the predictive
      performance for different HR levels by applying eight correction procedures,
      multiplying or dividing HRV parameters by the mean RR-interval (RRavg) to the
      power 0.5-16. Data collected from 1288 patients in The Finnish Cardiovascular
      Study (FINCAVAS), who satisfied the inclusion criteria, was used for the
      analyses. HRV parameters (RMSSD, VLF Power and LF Power) were calculated from 2
      min segment in the rest phase before exercise and 2-min recovery period
      immediately after peak exercise. Area under the receiver operating characteristic
      curve (AUC) was used to determine the predictive performance for each parameter
      with and without HR corrections in rest and recovery phases. The division of HRV
      parameters by segment's RRavg to the power 2 (HRVDIV-2) showed the highest
      predictive performance under the rest phase (RMSSD: 0.67/0.66; VLF Power:
      0.70/0.62; LF Power: 0.79/0.65; cardiac mortality/non-cardiac mortality) with
      minimum correlation to HR (r = -0.15 to 0.15). In the recovery phase, Kaplan
      Meier (KM) survival analysis revealed good risk stratification capacity at HRVDIV
      2 in both groups (cardiac and non-cardiac mortality). Although higher powers of
      correction (HRVDIV-4and HRVDIV-8) improved predictive performance during
      recovery, they induced an increased positive correlation to HR. Thus, we inferred
      that predictive capacity of HRV during rest and recovery is augmented when its
      dependence on HR is weakened by applying appropriate correction procedures. 

PMID- 24917827
TI  - A multistep procedure to prepare pre-vascularized cardiac tissue constructs using
      adult stem sells, dynamic cell cultures, and porous scaffolds.
AB  - The vascularization of tissue engineered products represents a key issue in
      regenerative medicine which needs to be addressed before the translation of these
      protocols to the bedside can be foreseen. Here we propose a multistep procedure
      to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using
      dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The
      strategy adopted exploits the peculiar differentiation potential of two distinct
      subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In
      the first step of the procedure, human mesenchymal stem cells (hMSCs) are seeded
      onto gelatin scaffolds to provide interconnected vessel-like structures, while
      human cardiomyocyte progenitor cells (hCMPCs) are stimulated in vitro to obtain
      their commitment toward the cardiac phenotype. The use of a modular bioreactor
      allows the perfusion of the whole scaffold, providing superior performance in
      terms of cardiac tissue maturation and cell survival. Both the cell culture on
      natural-derived polymers and the continuous medium perfusion of the scaffold led
      to the formation of a densely packaged proto-tissue composed of vascular-like and
      cardiac-like cells, which might complete maturation process and interconnect with
      native tissue upon in vivo implantation. In conclusion, the data obtained through
      the approach here proposed highlight the importance to provide stem cells with
      complementary signals in vitro able to resemble the complexity of cardiac
      microenvironment. 

PMID- 24917829
TI  - Genetic modification of the effects of exercise behavior on mental health.

PMID- 24917828
TI  - Caloric vestibular stimulation as a treatment for conversion disorder: a case
      report and medical hypothesis.
AB  - Conversion disorder is a medical condition in which a person has paralysis,
      blindness, or other neurological symptoms that cannot be clearly explained
      physiologically. To date, there is neither specific nor conclusive treatment. In
      this paper, we draw together a number of disparate pieces of knowledge to propose
      a novel intervention to provide transient alleviation for this condition. As
      caloric vestibular stimulation has been demonstrated to modulate a variety of
      cognitive functions associated with brain activations, especially in the temporal
      parietal cortex, anterior cingulate cortex, and insular cortex, there is evidence
      to assume an effect in specific mental disorders. Therefore, we go on to
      hypothesize that lateralized cold vestibular caloric stimulation will be
      effective in treating conversion disorder and we present provisional evidence
      from one patient that supports this conclusion. If our hypothesis is correct,
      this will be the first time in psychiatry and neurology that a clinically well
      known mental disorder, long considered difficult to understand and to treat, is
      relieved by a simple or common, non-invasive medical procedure. 

PMID- 24917826
TI  - Structure-function of proteins interacting with the alpha1 pore-forming subunit
      of high-voltage-activated calcium channels.
AB  - Openings of high-voltage-activated (HVA) calcium channels lead to a transient
      increase in calcium concentration that in turn activate a plethora of cellular
      functions, including muscle contraction, secretion and gene transcription. To
      coordinate all these responses calcium channels form supramolecular assemblies
      containing effectors and regulatory proteins that couple calcium influx to the
      downstream signal cascades and to feedback elements. According to the original
      biochemical characterization of skeletal muscle Dihydropyridine receptors, HVA
      calcium channels are multi-subunit protein complexes consisting of a pore-forming
      subunit (alpha1) associated with four additional polypeptide chains beta, alpha2,
      delta, and gamma, often referred to as accessory subunits. Twenty-five years
      after the first purification of a high-voltage calcium channel, the concept of a
      flexible stoichiometry to expand the repertoire of mechanisms that regulate
      calcium channel influx has emerged. Several other proteins have been identified
      that associate directly with the alpha1-subunit, including calmodulin and
      multiple members of the small and large GTPase family. Some of these proteins
      only interact with a subset of alpha1-subunits and during specific stages of
      biogenesis. More strikingly, most of the alpha1-subunit interacting proteins,
      such as the beta-subunit and small GTPases, regulate both gating and trafficking
      through a variety of mechanisms. Modulation of channel activity covers almost all
      biophysical properties of the channel. Likewise, regulation of the number of
      channels in the plasma membrane is performed by altering the release of the
      alpha1-subunit from the endoplasmic reticulum, by reducing its degradation or
      enhancing its recycling back to the cell surface. In this review, we discuss the
      structural basis, interplay and functional role of selected proteins that
      interact with the central pore-forming subunit of HVA calcium channels. 

PMID- 24917830
TI  - Speech is not special... again.

PMID- 24917832
TI  - Embodied mental rotation: a special link between egocentric transformation and
      the bodily self.
AB  - This experiment investigated the influence of motor expertise on object-based
      versus egocentric transformations in a chronometric mental rotation task using
      images of either the own or another person's body as stimulus material. According
      to the embodied cognition viewpoint, we hypothesized motor-experts to outperform
      non-motor experts specifically in the egocentric condition because of higher
      kinesthetic representation and motor simulations compared to object-based
      transformations. In line with this, we expected that images of the own body are
      solved faster than another person's body stimuli. Results showed a benefit of
      motor expertise and representations of another person's body, but only for the
      object-based transformation task. That is, this other-advantage diminishes in
      egocentric transformations. Since motor experts did not show any specific
      expertise in rotational movements, we concluded that using human bodies as
      stimulus material elicits embodied spatial transformations, which facilitates
      performance exclusively for egocentric transformations. Regarding stimulus
      material, the other-advantage ascribed to increased self-awareness-consciousness
      distracting attention-demanding resources, disappeared in the egocentric
      condition. This result may be due to the stronger link between the bodily self
      and motor representations compared to that emerging in object-based
      transformations. 

PMID- 24917833
TI  - Functional connectivity supporting the selective maintenance of feature-location
      binding in visual working memory.
AB  - Information on an object's features bound to its location is very important for
      maintaining object representations in visual working memory. Interactions with
      dynamic multi-dimensional objects in an external environment require complex
      cognitive control, including the selective maintenance of feature-location
      binding. Here, we used event-related functional magnetic resonance imaging to
      investigate brain activity and functional connectivity related to the maintenance
      of complex feature-location binding. Participants were required to detect task
      relevant changes in feature-location binding between objects defined by color,
      orientation, and location. We compared a complex binding task requiring complex
      feature-location binding (color-orientation-location) with a simple binding task
      in which simple feature-location binding, such as color-location, was task
      relevant and the other feature was task-irrelevant. Univariate analyses showed
      that the dorsolateral prefrontal cortex (DLPFC), hippocampus, and frontoparietal
      network were activated during the maintenance of complex feature-location
      binding. Functional connectivity analyses indicated cooperation between the
      inferior precentral sulcus (infPreCS), DLPFC, and hippocampus during the
      maintenance of complex feature-location binding. In contrast, the connectivity
      for the spatial updating of simple feature-location binding determined by
      reanalyzing the data from Takahama et al. (2010) demonstrated that the superior
      parietal lobule (SPL) cooperated with the DLPFC and hippocampus. These results
      suggest that the connectivity for complex feature-location binding does not
      simply reflect general memory load and that the DLPFC and hippocampus flexibly
      modulate the dorsal frontoparietal network, depending on the task requirements,
      with the infPreCS involved in the maintenance of complex feature-location binding
      and the SPL involved in the spatial updating of simple feature-location binding. 

PMID- 24917834
TI  - Fast phonetic learning in very young infants: what it shows, and what it doesn't
      show.

PMID- 24917831
TI  - The perception of odor objects in everyday life: a review on the processing of
      odor mixtures.
AB  - Smelling monomolecular odors hardly ever occurs in everyday life, and the daily
      functioning of the sense of smell relies primarily on the processing of complex
      mixtures of volatiles that are present in the environment (e.g., emanating from
      food or conspecifics). Such processing allows for the instantaneous recognition
      and categorization of smells and also for the discrimination of odors among
      others to extract relevant information and to adapt efficiently in different
      contexts. The neurophysiological mechanisms underpinning this highly efficient
      analysis of complex mixtures of odorants is beginning to be unraveled and support
      the idea that olfaction, as vision and audition, relies on odor-objects encoding.
      This configural processing of odor mixtures, which is empirically subject to
      important applications in our societies (e.g., the art of perfumers, flavorists,
      and wine makers), has been scientifically studied only during the last decades.
      This processing depends on many individual factors, among which are the
      developmental stage, lifestyle, physiological and mood state, and cognitive
      skills; this processing also presents striking similarities between species. The
      present review gathers the recent findings, as observed in animals, healthy
      subjects, and/or individuals with affective disorders, supporting the perception
      of complex odor stimuli as odor objects. It also discusses peripheral to central
      processing, and cognitive and behavioral significance. Finally, this review
      highlights that the study of odor mixtures is an original window allowing for the
      investigation of daily olfaction and emphasizes the need for knowledge about the
      underlying biological processes, which appear to be crucial for our
      representation and adaptation to the chemical environment. 

PMID- 24917835
TI  - Impulsive action: emotional impulses and their control.
AB  - This paper presents a novel theoretical view on impulsive action, integrating
      thus far separate perspectives on non-reflective action, motivation, emotion
      regulation, and impulse control. We frame impulsive action in terms of
      directedness of the individual organism toward, away, or against other givens -
      toward future states and away from one's present state. First, appraisal of a
      perceived or thought-of event or object on occasion, rapidly and without
      premonition or conscious deliberation, triggers a motive to modify one's relation
      to that event or object. Situational specifics of the event as perceived and
      appraised motivate and guide selection of readiness for a particular kind of
      purposive action. Second, perception of complex situations can give rise to
      multiple appraisals, multiple motives, and multiple simultaneous changes in
      action readiness. Multiple states of action readiness may interact in generating
      action, by reinforcing or attenuating each other, thereby yielding impulse
      control. We show how emotion control can itself result from a motive state or
      state of action readiness. Our view links impulsive action mechanistically to
      states of action readiness, which is the central feature of what distinguishes
      one kind of emotion from another. It thus provides a novel theoretical
      perspective to the somewhat fragmented literature on impulsive action. 

PMID- 24917836
TI  - Self-locomotion and spatial language and spatial cognition: insights from typical
      and atypical development.
AB  - Various studies have shown that occurrence of locomotion in infancy is correlated
      with the development of spatial cognitive competencies. Recent evidence suggests
      that locomotor experience might also be important for the development of spatial
      language. Together these findings suggest that locomotor experience might play a
      crucial role in the development of linguistic-cognitive spatial skills. However,
      some studies indicate that, despite their total deprivation of locomotor
      experience, young children with spinal muscular atrophy (SMA) have the capacity
      to acquire and use rich spatial representations including good spatial language.
      Nonetheless, we have to be cautious about what the striking performances
      displayed by SMA children can reveal on the link between motor and spatial
      development, as the dynamics of brain development in atypically developing
      children are different from typically developing children. 

PMID- 24917837
TI  - The emergence of embedded structure: insights from Kafr Qasem Sign Language.
AB  - This paper introduces data from Kafr Qasem Sign Language (KQSL), an as-yet
      undescribed sign language, and identifies the earliest indications of embedding
      in this young language. Using semantic and prosodic criteria, we identify
      predicates that form a constituent with a noun, functionally modifying it. We
      analyze these structures as instances of embedded predicates, exhibiting what can
      be regarded as very early stages in the development of subordinate constructions,
      and argue that these structures may bear directly on questions about the
      development of embedding and subordination in language in general. Deutscher
      (2009) argues persuasively that nominalization of a verb is the first step-and
      the crucial step-toward syntactic embedding. It has also been suggested that
      prosodic marking may precede syntactic marking of embedding (Mithun, 2009).
      However, the relevant data from the stage at which embedding first emerges have
      not previously been available. KQSL might be the missing piece of the puzzle: a
      language in which a noun can be modified by an additional predicate, forming a
      proposition within a proposition, sustained entirely by prosodic means. 

PMID- 24917838
TI  - Processing of syllable stress is functionally different from phoneme processing
      and does not profit from literacy acquisition.
AB  - Speech is characterized by phonemes and prosody. Neurocognitive evidence supports
      the separate processing of each type of information. Therefore, one might suggest
      individual development of both pathways. In this study, we examine literacy
      acquisition in middle childhood. Children become aware of the phonemes in speech
      at that time and refine phoneme processing when they acquire an alphabetic
      writing system. We test whether an enhanced sensitivity to phonemes in middle
      childhood extends to other aspects of the speech signal, such as prosody. To
      investigate prosodic processing, we used stress priming. Spoken stressed and
      unstressed syllables (primes) preceded spoken German words with stress on the
      first syllable (targets). We orthogonally varied stress overlap and phoneme
      overlap between the primes and onsets of the targets. Lexical decisions and Event
      Related Potentials (ERPs) for the targets were obtained for pre-reading
      preschoolers, reading pupils and adults. The behavioral and ERP results were
      largely comparable across all groups. The fastest responses were observed when
      the first syllable of the target word shared stress and phonemes with the
      preceding prime. ERP stress priming and ERP phoneme priming started 200 ms after
      the target word onset. Bilateral ERP stress priming was characterized by enhanced
      ERP amplitudes for stress overlap. Left-lateralized ERP phoneme priming
      replicates previously observed reduced ERP amplitudes for phoneme overlap. Groups
      differed in the strength of the behavioral phoneme priming and in the late ERP
      phoneme priming effect. The present results show that enhanced phonological
      processing in middle childhood is restricted to phonemes and does not extend to
      prosody. These results are indicative of two parallel processing systems for
      phonemes and prosody that might follow different developmental trajectories in
      middle childhood as a function of alphabetic literacy. 

PMID- 24917839
TI  - Achieving external validity in home advantage research: generalizing crowd noise
      effects.
AB  - Different factors have been postulated to explain the home advantage phenomenon
      in sport. One plausible explanation investigated has been the influence of a
      partisan home crowd on sports officials' decisions. Different types of studies
      have tested the crowd influence hypothesis including purposefully designed
      experiments. However, while experimental studies investigating crowd influences
      have high levels of internal validity, they suffer from a lack of external
      validity; decision-making in a laboratory setting bearing little resemblance to
      decision-making in live sports settings. This focused review initially considers
      threats to external validity in applied and theoretical experimental research.
      Discussing how such threats can be addressed using representative design by
      focusing on a recently published study that arguably provides the first
      experimental evidence of the impact of live crowd noise on officials in sport.
      The findings of this controlled experiment conducted in a real tournament setting
      offer a level of confirmation of the findings of laboratory studies in the area.
      Finally directions for future research and the future conduct of crowd noise
      studies are discussed. 

PMID- 24917841
TI  - Modeling a role of field of view in the extraction of geometric cues during
      reorientation.

PMID- 24917842
TI  - For a science of layered mechanisms: beyond laws, statistics, and correlations.
AB  - Two general claims are made in this work. First, we need several different layers
      of "theory," in particular for understanding human behavior. These layers should
      concern: the cognitive (mental) representations and mechanisms; the neural
      underlying processes; the evolutionary history and adaptive functions of our
      cognition and behaviors; the emergent and complex social structures and dynamics,
      their relation and feedbacks on individual minds and behaviors, and the
      relationship between internal regulating goals and the external functions/roles
      of our conduct; the historical and cultural mechanisms shaping our minds and
      behaviors; the developmental paths. Second, we do not just need "predictions" and
      "laws" but also "explanations"; that is, we need to identify the mechanisms
      producing (here-and-now, or diachronically) a given phenomenon. "Laws" are not
      enough; they are simply descriptive and predictive; we need the "why" and "how."
      Correlations are not enough (and they are frequently misleading). We need
      computational models of the processes postulated in our theories. 

PMID- 24917840
TI  - Distinct cortical locations for integration of audiovisual speech and the McGurk
      effect.
AB  - Audiovisual (AV) speech integration is often studied using the McGurk effect,
      where the combination of specific incongruent auditory and visual speech cues
      produces the perception of a third illusory speech percept. Recently, several
      studies have implicated the posterior superior temporal sulcus (pSTS) in the
      McGurk effect; however, the exact roles of the pSTS and other brain areas in
      "correcting" differing AV sensory inputs remain unclear. Using functional
      magnetic resonance imaging (fMRI) in ten participants, we aimed to isolate brain
      areas specifically involved in processing congruent AV speech and the McGurk
      effect. Speech stimuli were composed of sounds and/or videos of consonant-vowel
      tokens resulting in four stimulus classes: congruent AV speech (AVCong),
      incongruent AV speech resulting in the McGurk effect (AVMcGurk), acoustic-only
      speech (AO), and visual-only speech (VO). In group- and single-subject analyses,
      left pSTS exhibited significantly greater fMRI signal for congruent AV speech
      (i.e., AVCong trials) than for both AO and VO trials. Right superior temporal
      gyrus, medial prefrontal cortex, and cerebellum were also identified. For McGurk
      speech (i.e., AVMcGurk trials), two clusters in the left posterior superior
      temporal gyrus (pSTG), just posterior to Heschl's gyrus or on its border,
      exhibited greater fMRI signal than both AO and VO trials. We propose that while
      some brain areas, such as left pSTS, may be more critical for the integration of
      AV speech, other areas, such as left pSTG, may generate the "corrected" or merged
      percept arising from conflicting auditory and visual cues (i.e., as in the McGurk
      effect). These findings are consistent with the concept that posterior superior
      temporal areas represent part of a "dorsal auditory stream," which is involved in
      multisensory integration, sensorimotor control, and optimal state estimation
      (Rauschecker and Scott, 2009). 

PMID- 24917843
TI  - Contingencies and attentional capture: the importance of matching stimulus
      informativeness in the item-specific proportion congruent task.

PMID- 24917844
TI  - Trait-based cue Utilization and initial skill acquisition: implications for
      models of the progression to expertise.
AB  - The primary aim of this study was to examine the role of cue utilization in the
      initial acquisition of psycho-motor skills. Two experiments were undertaken, the
      first of which examined the relationship between cue utilization typologies and
      levels of accuracy following four simulated, power-off landing trials in a light
      aircraft simulator. The results indicated that higher levels of cue utilization
      were associated with a greater level of landing accuracy following training
      exposure. In the second study, participants' levels of cue utilization were
      assessed prior to two 15 min periods during which they practiced take-offs and
      landings using a simulated unmanned aerial vehicle (UAV). Consistent with Study
      1, the outcomes of Study 2 revealed a statistically significant relationship
      among levels of cue utilization and the number of trials to criterion on the take
      off task, and the proportion of successful trials during both take-off and
      landing. In combination, the results suggest that the capacity for the
      acquisition and the subsequent utilization of cues is an important predictor of
      skill acquisition, particularly during the initial stages of the process. The
      implications for theory and applied practice are discussed. 

PMID- 24917845
TI  - Heterogeneous timescales are spatially represented.

PMID- 24917846
TI  - Brain stimulation for combating Alzheimer's disease.

PMID- 24917847
TI  - The Correlation between Osteoporosis Occurrences in Both Schizophrenia and
      Parkinson's Disease.

PMID- 24917849
TI  - Chronic pain following physical and emotional trauma: the station nightclub fire.
AB  - OBJECTIVE: The purpose of this study was to evaluate factors associated with
      chronic pain in survivors of a large fire, including those with and without burn
      injury. METHODS: This study employed a survey-based cross-sectional design to
      evaluate data from survivors of The Station nightclub fire. The primary outcome
      measure was the presence and severity of pain. Multiple linear regressions with a
      stepwise approach were used to examine relationships among variables. Variables
      considered included age, gender, marital status, burn injury, total body surface
      area, skin graft, pre-morbid employment, time off work, return to same
      employment, depression (Beck depression inventory, BDI), and post-traumatic
      stress (impact of event scale - revised). RESULTS: Of 104 fire survivors, 27%
      reported pain at least 28 months after the event. Multiple factors associated
      with pain were assessed in the univariate analysis but only age (p = 0.012),
      graft (p = 0.009), and BDI score (p < 0.001) were significantly associated with
      pain in the multiple regression model. DISCUSSION: A significant number of fire
      survivors with and without burn injuries experienced chronic pain. Depth of burn
      and depression were significantly associated with pain outcome. Pain management
      should address both physical and emotional risk factors in this population.

PMID- 24917850
TI  - Monitoring of Cerebral Blood Flow and Metabolism Bedside in Patients with
      Subarachnoid Hemorrhage - A Xenon-CT and Microdialysis Study.
AB  - Cerebral ischemia is the leading cause of morbidity and mortality following
      aneurysmal subarachnoid hemorrhage (SAH). Although 70% of the patients show
      angiographic vasospasm only 30% develop symptomatic vasospasm defined as delayed
      cerebral ischemia (DCI). Early detection and management of reversible ischemia is
      of critical importance in patients with SAH. Using a bedside Xenon enhanced
      computerized tomography (Xenon-CT) scanner makes it possible to measure
      quantitative regional Cerebral blood flow (CBF) bedside in the neurointensive
      care setting and intracerebral microdialysis (MD) is a method that offers the
      possibility to monitor the metabolic state of the brain continuously. Here, we
      present results from nine SAH patients with both MD monitoring and bedside Xenon
      CT measurements. CBF measurements were performed within the first 72 h following
      bleeding. Six out of nine patients developed DCI at a later stage. Five out of
      six patients who developed DCI had initial global CBF below 26 ml/100 g/min
      whereas one had 53 ml/100 g/min. The three patients who did not develop clinical
      vasospasm all had initial global CBF above 27 ml/100 g/min. High lactate/pyruvate
      (L/P) ratio was associated with lower CBF values in the area surrounding the
      catheter. Five out of nine patients had L/P ratio >=25 and four of these patients
      had CBF <= 22 ml/100 g/min. These preliminary results suggest that patients with
      initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially
      low global CBF was accompanied with metabolic disturbances determined by the MD.
      Most importantly, pathological findings on the Xenon-CT and MD could be observed
      before any clinical signs of DCI. Combining bedside Xenon-CT and MD was found to
      be useful and feasible. Further studies are needed to evaluate if DCI can be
      detected before any other signs of DCI to prevent progress to infarction. 

PMID- 24917851
TI  - Therapeutic role and ligands of medium- to long-chain Fatty Acid receptors.
AB  - Medium- and long-chain free fatty acids (FFAs) are energy source for whole body
      and biological metabolites and components. In these decades, some research groups
      have reported that the biological functions of medium- to long-chain FFAs are
      exerted through G-protein coupled receptor designated free fatty acid receptor
      (FFAR). As the medium- to long-chain FFAs-activated FFARs, FFA1 and FFA4 are
      reported to be expressed widely in whole body and regulate various physiological
      processes. FFA1 expressed in pancreatic beta-cells has been shown to be involved
      in insulin secretion. FFA4 expressed in intestine, adipocytes, and macrophages
      has been shown to be involved in incretin secretion, differentiation, and anti
      inflammatory effect, respectively. These physiological functions have been
      focused on the treatment of metabolic disorders. In addition, these receptors
      have been also reported to be expressed in several other tissues such as
      intestine for FFA1, and tongue and stomach for FFA4. The recent functional
      studies indicated that they also contributed to energy homeostasis. Further, the
      number of synthetic compounds of FFA1 and FFA4 strongly promoted the
      physiological characterization of the receptors and their own therapeutic
      utility. In this article, we will discuss the recent progress regarding the
      therapeutic potential of these receptors and its ligands. 

PMID- 24917848
TI  - Mechanisms of body weight fluctuations in Parkinson's disease.
AB  - Typical body weight changes are known to occur in Parkinson's disease (PD).
      Weight loss has been reported in early stages as well as in advanced disease and
      malnutrition may worsen the clinical state of the patient. On the other hand, an
      increasing number of patients show weight gain under dopamine replacement therapy
      or after surgery. These weight changes are multifactorial and involve changes in
      energy expenditure, perturbation of homeostatic control, and eating behavior
      modulated by dopaminergic treatment. Comprehension of the different mechanisms
      contributing to body weight is a prerequisite for the management of body weight
      and nutritional state of an individual PD patient. This review summarizes the
      present knowledge and highlights the necessity of evaluation of body weight and
      related factors, as eating behavior, energy intake, and expenditure in PD. 

PMID- 24917852
TI  - Teleost microbiomes: the state of the art in their characterization, manipulation
      and importance in aquaculture and fisheries.
AB  - Indigenous microbiota play a critical role in the lives of their vertebrate
      hosts. In human and mouse models it is increasingly clear that innate and
      adaptive immunity develop in close concert with the commensal microbiome.
      Furthermore, several aspects of digestion and nutrient metabolism are governed by
      intestinal microbiota. Research on teleosts has responded relatively slowly to
      the introduction of massively parallel sequencing procedures in microbiomics.
      Nonetheless, progress has been made in biotic and gnotobiotic zebrafish models,
      defining a core microbiome and describing its role in development. However,
      microbiome research in other teleost species, especially those important from an
      aquaculture perspective, has been relatively slow. In this review, we examine
      progress in teleost microbiome research to date. We discuss teleost microbiomes
      in health and disease, microbiome ontogeny, prospects for successful microbiome
      manipulation (especially in an aquaculture setting) and attempt to identify
      important future research themes. We predict an explosion in research in this
      sector in line with the increasing global demand for fish protein, and the need
      to find sustainable approaches to improve aquaculture yield. The reduced cost and
      increasing ease of next generation sequencing technologies provides the
      technological backing, and the next 10 years will be an exciting time for teleost
      microbiome research. 

PMID- 24917853
TI  - The roles of lipids and nucleic acids in HIV-1 assembly.
AB  - During HIV-1 assembly, precursor Gag (PrGag) proteins are delivered to plasma
      membrane (PM) assembly sites, where they are triggered to oligomerize and bud
      from cells as immature virus particles. The delivery and triggering processes are
      coordinated by the PrGag matrix (MA) and nucleocapsid (NC) domains. Targeting of
      PrGag proteins to membranes enriched in cholesterol and phosphatidylinositol-4,5
      bisphosphate (PI[4,5]P2) is mediated by the MA domain, which also has been shown
      to bind both RNA and DNA. Evidence suggests that the nucleic-acid-binding
      function of MA serves to inhibit PrGag binding to inappropriate intracellular
      membranes, prior to delivery to the PM. At the PM, MA domains putatively trade
      RNA ligands for PI(4,5)P2 ligands, fostering high-affinity membrane binding.
      Triggering of oligomerization, budding, and virus particle release results when
      NC domains on adjacent PrGag proteins bind to viral RNA, leading to capsid (CA)
      domain oligomerization. This process leads to the assembly of immature virus
      shells in which hexamers of membrane-bound MA trimers appear to organize above
      interlinked CA hexamers. Here, we review the functions of retroviral MA proteins,
      with an emphasis on the nucleic-acid-binding capability of the HIV-1 MA protein,
      and its effects on membrane binding. 

PMID- 24917856
TI  - Lignocellulose-responsive bacteria in a southern California salt marsh identified
      by stable isotope probing.
AB  - Carbon cycling by microbes has been recognized as the main mechanism of organic
      matter decomposition and export in coastal wetlands, yet very little is known
      about the functional diversity of specific groups of decomposers (e.g., bacteria)
      in salt marsh benthic trophic structure. Indeed, salt marsh sediment bacteria
      remain largely in a black box in terms of their diversity and functional roles
      within salt marsh benthic food web pathways. We used DNA stable isotope probing
      (SIP) utilizing (13)C-labeled lignocellulose as a proxy to evaluate the fate of
      macrophyte-derived carbon in benthic salt marsh bacterial communities. Overall,
      146 bacterial species were detected using SIP, of which only 12 lineages were
      shared between enriched and non-enriched communities. Abundant groups from the
      (13)C-labeled community included Desulfosarcina, Spirochaeta, and Kangiella. This
      study is the first to use heavy-labeled lignocellulose to identify bacteria
      responsible for macrophyte carbon utilization in salt marsh sediments and will
      allow future studies to target specific lineages to elucidate their role in salt
      marsh carbon cycling and ultimately aid our understanding of the potential of
      salt marshes to store carbon. 

PMID- 24917855
TI  - Specificity of plant-microbe interactions in the tree mycorrhizosphere biome and
      consequences for soil C cycling.
AB  - Mycorrhizal associations are ubiquitous and form a substantial component of the
      microbial biomass in forest ecosystems and fluxes of C to these belowground
      organisms account for a substantial portion of carbon assimilated by forest
      vegetation. Climate change has been predicted to alter belowground plant
      allocated C which may cause compositional shifts in soil microbial communities,
      and it has been hypothesized that this community change will influence C
      mitigation in forest ecosystems. Some 10,000 species of ectomycorrhizal fungi are
      currently recognized, some of which are host specific and will only associate
      with a single tree species, for example, Suillus grevillei with larch.
      Mycorrhizae are a strong sink for plant C, differences in mycorrhizal anatomy,
      particularly the presence and extent of emanating hyphae, can affect the amount
      of plant C allocated to these assemblages. Mycorrhizal morphology affects not
      only spatial distribution of C in forests, but also differences in the longevity
      of these diverse structures may have important consequences for C sequestration
      in soil. Mycorrhizal growth form has been used to group fungi into distinctive
      functional groups that vary qualitatively and spatially in their foraging and
      nutrient acquiring potential. Through new genomic techniques we are beginning to
      understand the mechanisms involved in the specificity and selection of
      ectomycorrhizal associations though much less is known about arbuscular
      mycorrhizal associations. In this review we examine evidence for tree species-
      mycorrhizal specificity, and the mechanisms involved (e.g., signal compounds). We
      also explore what is known about the effects of these associations and
      interactions with other soil organisms on the quality and quantity of C flow into
      the mycorrhizosphere (the area under the influence of mycorrhizal root tips),
      including spatial and seasonal variations. The enormity of the mycorrhizosphere
      biome in forests and its potential to sequester substantial C belowground
      highlights the vital importance of increasing our knowledge of the dynamics of
      the different mycorrhizal functional groups in diverse forests. 

PMID- 24917858
TI  - The feasibility of automated online flow cytometry for in-situ monitoring of
      microbial dynamics in aquatic ecosystems.
AB  - Fluorescent staining coupled with flow cytometry (FCM) is often used for the
      monitoring, quantification and characterization of bacteria in engineered and
      environmental aquatic ecosystems including seawater, freshwater, drinking water,
      wastewater, and industrial bioreactors. However, infrequent grab sampling hampers
      accurate characterization and subsequent understanding of microbial dynamics in
      all of these ecosystems. A logic technological progression is high throughput and
      full automation of the sampling, staining, measurement, and data analysis steps.
      Here we assess the feasibility and applicability of automated FCM by means of
      actual data sets produced with prototype instrumentation. As proof-of-concept we
      demonstrate examples of microbial dynamics in (i) flowing tap water from a
      municipal drinking water supply network and (ii) river water from a small creek
      subject to two rainfall events. In both cases, automated measurements were done
      at 15-min intervals during 12-14 consecutive days, yielding more than 1000
      individual data points for each ecosystem. The extensive data sets derived from
      the automated measurements allowed for the establishment of baseline data for
      each ecosystem, as well as for the recognition of daily variations and specific
      events that would most likely be missed (or miss-characterized) by infrequent
      sampling. In addition, the online FCM data from the river water was combined and
      correlated with online measurements of abiotic parameters, showing considerable
      potential for a better understanding of cause-and-effect relationships in aquatic
      ecosystems. Although several challenges remain, the successful operation of an
      automated online FCM system and the basic interpretation of the resulting data
      sets represent a breakthrough toward the eventual establishment of fully
      automated online microbiological monitoring technologies. 

PMID- 24917854
TI  - The importance of the viable but non-culturable state in human bacterial
      pathogens.
AB  - Many bacterial species have been found to exist in a viable but non-culturable
      (VBNC) state since its discovery in 1982. VBNC cells are characterized by a loss
      of culturability on routine agar, which impairs their detection by conventional
      plate count techniques. This leads to an underestimation of total viable cells in
      environmental or clinical samples, and thus poses a risk to public health. In
      this review, we present recent findings on the VBNC state of human bacterial
      pathogens. The characteristics of VBNC cells, including the similarities and
      differences to viable, culturable cells and dead cells, and different detection
      methods are discussed. Exposure to various stresses can induce the VBNC state,
      and VBNC cells may be resuscitated back to culturable cells under suitable
      stimuli. The conditions that trigger the induction of the VBNC state and
      resuscitation from it are summarized and the mechanisms underlying these two
      processes are discussed. Last but not least, the significance of VBNC cells and
      their potential influence on human health are also reviewed. 

PMID- 24917857
TI  - Fracture zones in the Mid Atlantic Ridge lead to alterations in prokaryotic and
      viral parameters in deep-water masses.
AB  - We hypothesized that mixing zones of deep-water masses act as ecotones leading to
      alterations in microbial diversity and activity due to changes in the
      biogeochemical characteristics of these boundary systems. We determined the
      changes in prokaryotic and viral abundance and production in the Vema Fracture
      Zone (VFZ) of the subtropical North Atlantic Ocean, where North Atlantic Deep
      Water (NADW) and Antarctic Bottom Water (AABW) are funneled through this narrow
      canyon and therefore, are subjected to intense vertical mixing. Consequently,
      salinity, potential temperature, oxygen, PO4, SiO4, NO3 were altered in the NADW
      inside the VFZ as compared to the NADW outside of the VFZ. Also, viral abundance,
      lytic viral production (VP) and the virus-to-prokaryote ratio (VPR) were elevated
      in the NADW in the VFZ as compared to the NADW outside the VFZ. In contrast to
      lytic VP, lysogenic VP and both the frequency of lytically (FIC) and
      lysogenically infected cells (FLC) did not significantly differ between in- and
      outside the VFZ. Generally, FIC was higher than FLC throughout the water column.
      Prokaryotic (determined by T-RFLP) and viral (determined by RAPD-PCR) community
      composition was depth-stratified inside and outside the VFZ. The viral community
      was more modified both with depth and over distance inside the VFZ as compared to
      the northern section and to the prokaryotic communities. However, no clusters of
      prokaryotic and viral communities characteristic for the VFZ were identified.
      Based on our observations, we conclude that turbulent mixing of the deep water
      masses impacts not only the physico-chemical parameters of the mixing zone but
      also the interaction between viruses and prokaryotes due to a stimulation of the
      overall activity. However, only minor effects of deep water mixing were observed
      on the community composition of the dominant prokaryotes and viruses. 

PMID- 24917859
TI  - Stress responses in flavivirus-infected cells: activation of unfolded protein
      response and autophagy.
AB  - The Flavivirus is a genus of RNA viruses that includes multiple long known human,
      animal, and zoonotic pathogens such as Dengue virus, yellow fever virus, West
      Nile virus, or Japanese encephalitis virus, as well as other less known viruses
      that represent potential threats for human and animal health such as Usutu or
      Zika viruses. Flavivirus replication is based on endoplasmic reticulum-derived
      structures. Membrane remodeling and accumulation of viral factors induce
      endoplasmic reticulum stress that results in activation of a cellular signaling
      response termed unfolded protein response (UPR), which can be modulated by the
      viruses for their own benefit. Concomitant with the activation of the UPR, an
      upregulation of the autophagic pathway in cells infected with different
      flaviviruses has also been described. This review addresses the current knowledge
      of the relationship between endoplasmic reticulum stress, UPR, and autophagy in
      flavivirus-infected cells and the growing evidences for an involvement of these
      cellular pathways in the replication and pathogenesis of these viruses. 

PMID- 24917860
TI  - Planctomycetes and macroalgae, a striking association.
AB  - Planctomycetes are part of the complex microbial biofilm community of a wide
      range of macroalgae. Recently, some studies began to unveil the great diversity
      of Planctomycetes present in this microenvironment and the interactions between
      the two organisms. Culture dependent and independent methods revealed the
      existence of a great number of species but, so far, only less than 10 species
      have been isolated. Planctomycetes comprise the genera Rhodopirellula,
      Blastopirellula, and Planctomyces, Phycisphaera and the uncultured class OM190
      and some other taxa have only been found in this association. Several factors
      favor the colonization of macroalgal surfaces by planctomycetes. Many species
      possess holdfasts for attachment. The macroalgae secrete various sulfated
      polysaccharides that are the substrate for the abundant sulfatases produced by
      planctomycetes. Specificity between planctomycetes and macroalgae seem to exist
      which may be related to the chemical nature of the polysaccharides produced by
      each macroalga. Furthermore, the peptidoglycan-free cell wall of planctomycetes
      allows them to resist the action of several antimicrobial compounds produced by
      the macroalgae or other bacteria in the biofilm community that are effective
      against biofouling by other microorganisms. Despite the increase in our knowledge
      on the successful planctomycetes-macroalgae association, a great effort to fully
      understand this interaction is needed. 

PMID- 24917861
TI  - The role of acetogens in microbially influenced corrosion of steel.
AB  - Microbially influenced corrosion (MIC) of iron (Fe(0)) by sulfate-reducing
      bacteria (SRB) has been studied extensively. Through a mechanism, that is still
      poorly understood, electrons or hydrogen (H2) molecules are removed from the
      metal surface and used as electron donor for sulfate reduction. The resulting
      ferrous ions precipitate in part with the sulfide produced, forming
      characteristic black iron sulfide. Hydrogenotrophic methanogens can also
      contribute to MIC. Incubation of pipeline water samples, containing bicarbonate
      and some sulfate, in serum bottles with steel coupons and a headspace of 10%
      (vol/vol) CO2 and 90% N2, indicated formation of acetate and methane. Incubation
      of these samples in serum bottles, containing medium with coupons and bicarbonate
      but no sulfate, also indicated that formation of acetate preceded the formation
      of methane. Microbial community analyses of these enrichments indicated the
      presence of Acetobacterium, as well as of hydrogenotrophic and acetotrophic
      methanogens. The formation of acetate by homoacetogens, such as Acetobacterium
      woodii from H2 (or Fe(0)) and CO2, is potentially important, because acetate is a
      required carbon source for many SRB growing with H2 and sulfate. A consortium of
      the SRB Desulfovibrio vulgaris Hildenborough and A. woodii was able to grow in
      defined medium with H2, CO2, and sulfate, because A. woodii provides the acetate,
      needed by D. vulgaris under these conditions. Likewise, general corrosion rates
      of metal coupons incubated with D. vulgaris in the presence of acetate or in the
      presence of A. woodii were higher than in the absence of acetate or A. woodii,
      respectively. An extended MIC model capturing these results is presented. 

PMID- 24917863
TI  - Epitope-specific antibody levels in tuberculosis: biomarkers of protection,
      disease, and response to treatment.
AB  - Monoclonal antibodies restricted to Mycobacterium tuberculosis can measure
      epitope-specific antibody levels in a competition assay. Immunodominant epitopes
      were defined from clinical samples and related to the clinical spectrum of
      disease. Antibody to the immunodominant epitopes was associated with HLA-DR15.
      Occupational exposure showed a different response and was consistent with
      recognition of dormancy-related proteins and protection despite exposure to
      tuberculosis (TB). Studies in leprosy revealed the importance of immune deviation
      and the relationships between T and B cell epitopes. During treatment, antibody
      levels increased, epitope spreading occurred, but the affinity constants remained
      the same after further antigen exposure, suggesting constraints on the process of
      epitope selection. Epitope-specific antibody levels have a potential role as
      biomarkers for new vaccines which might prevent the progression of latent to
      active TB and as tools to measure treatment effects on subpopulations of tubercle
      bacilli. 

PMID- 24917862
TI  - Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems.
AB  - The NKR-P1 receptors were identified as prototypical natural killer (NK) cell
      surface antigens and later shown to be conserved from rodents to humans on NK
      cells and subsets of T cells. C-type lectin-like in nature, they were originally
      shown to be capable of activating NK cell function and to recognize ligands on
      tumor cells. However, certain family members have subsequently been shown to be
      capable of inhibiting NK cell activity, and to recognize proteins encoded by a
      family of genetically linked C-type lectin-related ligands. Some of these ligands
      are expressed by normal, healthy cells, and modulated during transformation,
      infection, and cellular stress, while other ligands are upregulated during the
      immune response and during pathological circumstances. Here, we discuss
      historical and recent developments in NKR-P1 biology that demonstrate this NK
      receptor-ligand system to be far more complex and diverse than originally
      anticipated. 

PMID- 24917864
TI  - Immunologic Basis for Long HCDR3s in Broadly Neutralizing Antibodies Against HIV
      1.
AB  - A large number of potent broadly neutralizing antibodies (bnAbs) against HIV-1
      have been reported in recent years, raising hope for the possibility of an
      effective vaccine based on epitopes recognized by these protective antibodies.
      However, many of these bnAbs contain the long heavy chain complementarity
      determining region 3 (HCDR3), which is viewed as an obstacle to the development
      of an HIV-1 vaccine targeting the bnAb responses. This mini-review summarizes the
      current literature and discusses the different potential immunologic mechanisms
      for generating long HCDR3, including D-D fusion, VH replacement, long N region
      addition, and skewed D-J gene usage, among which potential VH replacement
      products appear to be significant contributors. VH replacement occurs through
      recombinase activated gene-mediated secondary recombination and contributes to
      the diversified naive B cell repertoire. During VH replacement, a short stretch
      of nucleotides from previously rearranged VH genes remains within the newly
      formed HCDR3, thus elongating its length. Accumulating evidence suggests that
      long HCDR3s are present in significant numbers in the human mature naive B cell
      repertoire and are primarily generated by recombination during B cell
      development. These new observations indicate that long HCDR3s, though low in
      frequency, are a normal feature of the human antibody naive repertoire and they
      appear to be selected to target conserved epitopes located in deep, partially
      obscured regions of the HIV-1 envelope trimer. Therefore, the presence of long
      HCDR3 sequences should not necessarily be viewed as an obstacle to the
      development of an HIV-1 vaccine based upon bnAb responses. 

PMID- 24917865
TI  - Immune defects in the risk of infection and response to vaccination in monoclonal
      gammopathy of undetermined significance and multiple myeloma.
AB  - The plasma cell proliferative disorders monoclonal gammopathy of undetermined
      significance (MGUS) and malignant multiple myeloma (MM) are characterized by an
      accumulation of transformed clonal plasma cells in the bone marrow and production
      of monoclonal immunoglobulin. They typically affect an older population, with
      median age of diagnosis of approximately 70 years. In both disorders, there is an
      increased risk of infection due to the immunosuppressive effects of disease and
      conjointly of therapy in MM, and response to vaccination to counter infection is
      compromised. The underlying factors in a weakened immune response in MGUS and MM
      are as yet not fully understood. A confounding factor is the onset of normal
      aging, which quantitatively and qualitatively hampers humoral immunity to affect
      response to infection and vaccination. In this review, we examine the status of
      immune alterations in MGUS and MM and set these against normal aging immune
      responses. We focus primarily on quantitative and functional aspects of B-cell
      immunity. Furthermore, we review the current knowledge relating to susceptibility
      to infectious disease in MGUS and MM, and how efficacy of conventional
      vaccination is affected by proliferative disease-related and therapy-related
      factors. 

PMID- 24917866
TI  - The role of natural killer cells and CD8(+) T cells in hepatitis B virus
      infection.
AB  - Hepatitis B virus (HBV) infection is one of the main causes of chronic liver
      diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host
      immune responses are important factors that determine whether HBV infection is
      cleared or persists. Natural killer (NK) cells represent the main effector
      population of the innate immune system and are abundant in the human liver.
      Recently, it has been demonstrated that NK cells not only exhibit antiviral
      functions but may also regulate adaptive immune responses by deletion of HBV
      specific CD8(+) T cells. It is well-established that HBV-specific CD8(+) T cells
      contribute to virus elimination. However, the mechanisms contributing to CD8(+) T
      cell failure in chronic HBV infection are not well-understood. In this review, we
      will summarize the current knowledge about NK cells and CD8(+) T cells and
      illustrate their contribution to viral clearance and persistence in HBV
      infection. Moreover, novel immunological in vitro model systems and techniques to
      analyze HBV-specific CD8(+) T cells, which are barely detectable using current
      multimer staining methods, will be discussed. 

PMID- 24917867
TI  - Does antigen masking by ubiquitin chains protect from the development of
      autoimmune diseases?
AB  - Autoimmune diseases are characterized by the production of antibodies against
      self-antigens and generally arise from a failure of central or peripheral
      tolerance. However, these diseases may develop when newly appearing antigens are
      not recognized as self by the immune system. The mechanism by which some antigens
      are "invisible" to the immune system is not completely understood. Apoptotic and
      complement system defects or autophagy imbalance can generate this antigenic
      autoreactivity. Under particular circumstances, cellular debris containing
      autoreactive antigens can be recognized by innate immune receptors or other
      sensors and can eventually lead to autoimmunity. Ubiquitination may be one of the
      mechanisms protecting autoreactive antigens from the immune system that, if
      disrupted, can lead to autoimmunity. Ubiquitination is an essential post
      translational modification used by cells to target proteins for degradation or to
      regulate other intracellular processes. The level of ubiquitination is regulated
      during T cell tolerance and apoptosis and E3 ligases have emerged as a crucial
      signaling pathway for the regulation of T cell tolerance toward self-antigens. I
      propose here that an unrecognized role of ubiquitin and ubiquitin-like proteins
      could be to render intracellular or foreign antigens (present in cellular debris
      resulting from apoptosis, complement system, or autophagy defects) invisible to
      the immune system in order to prevent the development of autoimmunity. 

PMID- 24917868
TI  - Immunoglobulin gene repertoire diversification and selection in the stomach -
      from gastritis to gastric lymphomas.
AB  - Chronic gastritis is characterized by gastric mucosal inflammation due to
      autoimmune responses or infection, frequently with Helicobacter pylori. Gastritis
      with H. pylori background can cause gastric mucosa-associated lymphoid tissue
      lymphoma (MALT-L), which sometimes further transforms into diffuse large B-cell
      lymphoma (DLBCL). However, gastric DLBCL can also be initiated de novo. The
      mechanisms underlying transformation into DLBCL are not completely understood. We
      analyzed immunoglobulin repertoires and clonal trees to investigate whether and
      how immunoglobulin gene repertoires, clonal diversification, and selection in
      gastritis, gastric MALT-L, and DLBCL differ from each other and from normal
      responses. The two gastritis types (positive or negative for H. pylori) had
      similarly diverse repertoires. MALT-L dominant clones (defined as the largest
      clones in each sample) presented higher diversification and longer mutational
      histories compared with all other conditions. DLBCL dominant clones displayed
      lower clonal diversification, suggesting the transforming events are triggered by
      similar responses in different patients. These results are surprising, as we
      expected to find similarities between the dominant clones of gastritis and MALT-L
      and between those of MALT-L and DLBCL. 

PMID- 24917869
TI  - The role of the cell wall compartment in mutualistic symbioses of plants.
AB  - Plants engage in mutualistic interactions with microbes that improve their
      mineral nutrient supply. The most wide-spread symbiotic association is arbuscular
      mycorrhiza (AM), in which fungi of the order Glomeromycota invade roots and
      colonize the cellular lumen of cortical cells. The establishment of this
      interaction requires a dedicated molecular-genetic program and a cellular
      machinery of the plant host. This program is partially shared with the root
      nodule symbiosis (RNS), which involves prokaryotic partners collectively referred
      to as rhizobia. Both, AM and RNS are endosymbioses that involve intracellular
      accommodation of the microbial partner in the cells of the plant host. Since
      plant cells are surrounded by sturdy cell walls, root penetration and cell
      invasion requires mechanisms to overcome this barrier while maintaining the
      cytoplasm of the two partners separate during development of the symbiotic
      association. Here, we discuss the diverse functions of the cell wall compartment
      in establishment and functioning of plant symbioses with the emphasis on AM and
      RNS, and we describe the stages of the AM association between the model organisms
      Petunia hybrida and Rhizophagus irregularis. 

PMID- 24917870
TI  - Integrating omic approaches for abiotic stress tolerance in soybean.
AB  - Soybean production is greatly influenced by abiotic stresses imposed by
      environmental factors such as drought, water submergence, salt, and heavy metals.
      A thorough understanding of plant response to abiotic stress at the molecular
      level is a prerequisite for its effective management. The molecular mechanism of
      stress tolerance is complex and requires information at the omic level to
      understand it effectively. In this regard, enormous progress has been made in the
      omics field in the areas of genomics, transcriptomics, and proteomics. The
      emerging field of ionomics is also being employed for investigating abiotic
      stress tolerance in soybean. Omic approaches generate a huge amount of data, and
      adequate advancements in computational tools have been achieved for effective
      analysis. However, the integration of omic-scale information to address complex
      genetics and physiological questions is still a challenge. In this review, we
      have described advances in omic tools in the view of conventional and modern
      approaches being used to dissect abiotic stress tolerance in soybean. Emphasis
      was given to approaches such as quantitative trait loci (QTL) mapping, genome
      wide association studies (GWAS), and genomic selection (GS). Comparative genomics
      and candidate gene approaches are also discussed considering identification of
      potential genomic loci, genes, and biochemical pathways involved in stress
      tolerance mechanism in soybean. This review also provides a comprehensive catalog
      of available online omic resources for soybean and its effective utilization. We
      have also addressed the significance of phenomics in the integrated approaches
      and recognized high-throughput multi-dimensional phenotyping as a major limiting
      factor for the improvement of abiotic stress tolerance in soybean. 

PMID- 24917871
TI  - The new insights into cadmium sensing.
AB  - Cadmium (Cd) is non-essential heavy metal, which in excess, exhibits deleterious
      effects to the most of the organisms. Mobilization of defense mechanisms against
      this toxic agent requires rapid activation of signaling pathways. The article
      presents recent advances in the research concerning cadmium signal transduction
      in plants. New insights into the involvement of reactive oxygen species (ROS),
      nitric oxide (NO), plant growth regulators, and Cd-induced protein modifications
      are reviewed. Moreover, the role of recently recognized Cd-associated signal
      elements, including micro RNAs and several cis- and trans-acting elements is
      discussed. 

PMID- 24917873
TI  - Epigenetic regulation of bud dormancy events in perennial plants.
AB  - Release of bud dormancy in perennial plants resembles vernalization in
      Arabidopsis thaliana and cereals. In both cases, a certain period of chilling is
      required for accomplishing the reproductive phase, and several transcription
      factors with the MADS-box domain perform a central regulatory role in these
      processes. The expression of DORMANCY-ASSOCIATED MADS-box (DAM)-related genes has
      been found to be up-regulated in dormant buds of numerous plant species, such as
      poplar, raspberry, leafy spurge, blackcurrant, Japanese apricot, and peach.
      Moreover, functional evidence suggests the involvement of DAM genes in the
      regulation of seasonal dormancy in peach. Recent findings highlight the presence
      of genome-wide epigenetic modifications related to dormancy events, and more
      specifically the epigenetic regulation of DAM-related genes in a similar way to
      FLOWERING LOCUS C, a key integrator of vernalization effectors on flowering
      initiation in Arabidopsis. We revise the most relevant molecular and genomic
      contributions in the field of bud dormancy, and discuss the increasing evidence
      for chromatin modification involvement in the epigenetic regulation of seasonal
      dormancy cycles in perennial plants. 

PMID- 24917875
TI  - A biologist, a statistician, and a bioinformatician walk into a conference
      room... and walk out with a great metagenomics project plan.

PMID- 24917874
TI  - Uncovering plant-pathogen crosstalk through apoplastic proteomic studies.
AB  - Plant pathogens have evolved by developing different strategies to infect their
      host, which in turn have elaborated immune responses to counter the pathogen
      invasion. The apoplast, including the cell wall and extracellular space outside
      the plasma membrane, is one of the first compartments where pathogen-host
      interaction occurs. The plant cell wall is composed of a complex network of
      polysaccharides polymers and glycoproteins and serves as a natural physical
      barrier against pathogen invasion. The apoplastic fluid, circulating through the
      cell wall and intercellular spaces, provides a means for delivering molecules and
      facilitating intercellular communications. Some plant-pathogen interactions lead
      to plant cell wall degradation allowing pathogens to penetrate into the cells. In
      turn, the plant immune system recognizes microbial- or damage-associated
      molecular patterns (MAMPs or DAMPs) and initiates a set of basal immune
      responses, including the strengthening of the plant cell wall. The establishment
      of defense requires the regulation of a wide variety of proteins that are
      involved at different levels, from receptor perception of the pathogen via
      signaling mechanisms to the strengthening of the cell wall or degradation of the
      pathogen itself. A fine regulation of apoplastic proteins is therefore essential
      for rapid and effective pathogen perception and for maintaining cell wall
      integrity. This review aims to provide insight into analyses using proteomic
      approaches of the apoplast to highlight the modulation of the apoplastic protein
      patterns during pathogen infection and to unravel the key players involved in
      plant-pathogen interaction. 

PMID- 24917876
TI  - Characterization of HPV DNA methylation of contiguous CpG sites by bisulfite
      treatment and massively parallel sequencing-the FRAGMENT approach.
AB  - Invasive cervix cancer (ICC) is the third most common malignant tumor in women
      and human papillomavirus 16 (HPV16) causes more than 50% of ICC. DNA methylation
      is a covalent modification predominantly occurring at CpG dinucleotides and
      increased methylation across the HPV16 genome is strongly associated with ICC
      development. Next generation (Next Gen) sequencing has been proposed as a novel
      approach to determine DNA methylation. However, utilization of this method to
      survey CpG methylation in the HPV16 genome is not well described. Moreover, it
      provides additional information on methylation "haplotypes." In the current
      study, we chose 12 random samples, amplified multiple segments in the HPV16
      bisulfite treated genome with specific barcodes, inspected the methylation ratio
      at 31 CpG sites for all samples using Illumina sequencing, and compared the
      results with quantitative pyrosequencing. Most of the CpG sites were highly
      consistent between the two approaches (overall correlation, r = 0.92), thus
      verifying that Next Gen sequencing is an accurate and convenient method to survey
      HPV16 methylation and thus can be used in clinical samples for risk assessment.
      Moreover, the CpG methylation patterns (methylation haplotypes) in single
      molecules identified an excess of complete-and non-methylated molecules and a
      substantial amount of partial-methylated ones, thus indicating a complex dynamic
      for the mechanisms of HPV16 CpG methylation. In summary, the advantages of Next
      Gen sequencing compared to pyrosequencing for HPV genome methylation analyses
      include higher throughput, increased resolution, and improved efficiency of time
      and resources. 

PMID- 24917877
TI  - Copy number variants and selective sweeps in natural populations of the house
      mouse (Mus musculus domesticus).
AB  - Copy-number variants (CNVs) may play an important role in early adaptations,
      potentially facilitating rapid divergence of populations. We describe an approach
      to study this question by investigating CNVs present in natural populations of
      mice in the early stages of divergence and their involvement in selective sweeps.
      We have analyzed individuals from two recently diverged natural populations of
      the house mouse (Mus musculus domesticus) from Germany and France using custom,
      high-density, comparative genome hybridization arrays (CGH) that covered almost
      164 Mb and 2444 genes. One thousand eight hundred and sixty one of those genes we
      previously identified as differentially expressed between these populations,
      while the expression of the remaining genes was invariant. In total, we
      identified 1868 CNVs across all 10 samples, 200 bp to 600 kb in size and
      affecting 424 genic regions. Roughly two thirds of all CNVs found were deletions.
      We found no enrichment of CNVs among the differentially expressed genes between
      the populations compared to the invariant ones, nor any meaningful correlation
      between CNVs and gene expression changes. Among the CNV genes, we found cellular
      component gene ontology categories of the synapse overrepresented among all the
      2444 genes tested. To investigate potential adaptive significance of the CNV
      regions, we selected six that showed large differences in frequency of CNVs
      between the two populations and analyzed variation in at least two
      microsatellites surrounding the loci in a sample of 46 unrelated animals from the
      same populations collected in field trappings. We identified two loci with large
      differences in microsatellite heterozygosity (Sfi1 and Glo1/Dnahc8 regions) and
      one locus with low variation across the populations (Cmah), thus suggesting that
      these genomic regions might have recently undergone selective sweeps.
      Interestingly, the Glo1 CNV has previously been implicated in anxiety-like
      behavior in mice, suggesting a differential evolution of a behavioral trait. 

PMID- 24917878
TI  - Fetal alcohol spectrum disorders and their transmission through genetic and
      epigenetic mechanisms.
AB  - Fetal alcohol spectrum disorders (FASD) are a group of related conditions that
      arise from prenatal exposure to maternal consumption of the teratogen, ethanol.
      It has been estimated that roughly 1% of children in the US suffer from FASD
      (Sampson etal., 1997), though in some world populations, such as inhabitants of
      some poorer regions of South Africa, the rate can climb to as high as 20% (May
      etal., 2013). FASD are the largest cause of mental retardation in U.S. neonates,
      and ironically, are entirely preventable. FASD have been linked to major changes
      in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in lifelong
      impairments through mental disorders, retardation, and sensitivity to stress.
      FASD are linked to an impaired immune system which consequently leads to an
      elevated risk of cancer and other diseases. FASD arise from a complex interplay
      of genetic and epigenetic factors. Here, we review current literature on the
      topic to tease apart what is known in these areas particularly emphasizing HPA
      axis dysfunction and how this ties into new studies of transgenerational
      inheritance in FASD. 

PMID- 24917879
TI  - Transfer RNA and human disease.
AB  - Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and
      result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA)
      genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations
      have been linked to various disease states. Often these mutations prevent tRNA
      aminoacylation. Disrupting this primary function affects protein synthesis and
      the expression, folding, and function of oxidative phosphorylation enzymes.
      Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to
      cellular energetics, including COX deficiency (cytochrome C oxidase),
      mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and
      MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
      episodes). Diseases caused by mt-tRNA mutations can also affect very specific
      tissue types, as in the case of neurosensory non-syndromic hearing loss and
      pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy.
      Importantly, mitochondrial heteroplasmy plays a role in disease severity and age
      of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic
      and mitochondrial tRNAs are also linked to a diverse range of clinical
      phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated
      modifying enzymes can also impact tRNA expression and abundance, tRNA
      modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of
      these pathological mutations in tRNAs and processing enzymes are likely to affect
      non-canonical tRNA functions, and contribute to the diseases without
      significantly impacting on translation. This chapter will review recent
      literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes
      that process tRNAs, to human disease. We explore the mechanisms involved in the
      clinical presentation of these various diseases with an emphasis on neurological
      disease. 

PMID- 24917880
TI  - Genetic analysis of long-lived families reveals novel variants influencing high
      density-lipoprotein cholesterol.
AB  - The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse
      relationship to the risks of atherosclerosis and cardiovascular disease (CVD),
      and have also been associated with longevity. We sought to identify novel loci
      for HDL that could potentially provide new insights into biological regulation of
      HDL metabolism in healthy-longevous subjects. We performed a genome-wide
      association (GWA) scan on HDL using a mixed model approach to account for family
      structure using kinship coefficients. A total of 4114 subjects of European
      descent (480 families) were genotyped at ~2.3 million SNPs and ~38 million SNPs
      were imputed using the 1000 Genome Cosmopolitan reference panel in MACH. We
      identified novel variants near-NLRP1 (17p13) associated with an increase of HDL
      levels at genome-wide significant level (p < 5.0E-08). Additionally, several CETP
      (16q21) and ZNF259-APOA5-A4-C3-A1 (11q23.3) variants associated with HDL were
      found, replicating those previously reported in the literature. A possible
      regulatory variant upstream of NLRP1 that is associated with HDL in these elderly
      Long Life Family Study (LLFS) subjects may also contribute to their longevity and
      health. Our NLRP1 intergenic SNPs show a potential regulatory function in
      Encyclopedia of DNA Elements (ENCODE); however, it is not clear whether they
      regulate NLRP1 or other more remote gene. NLRP1 plays an important role in the
      induction of apoptosis, and its inflammasome is critical for mediating innate
      immune responses. Nlrp1a (a mouse ortholog of human NLRP1) interacts with SREBP
      1a (17p11) which has a fundamental role in lipid concentration and composition,
      and is involved in innate immune response in macrophages. The NLRP1 region is
      conserved in mammals, but also has evolved adaptively showing signals of positive
      selection in European populations that might confer an advantage. NLRP1
      intergenic SNPs have also been associated with immunity/inflammasome disorders
      which highlights the biological importance of this chromosomal region. 

PMID- 24917881
TI  - Long-term genomic and epigenomic dysregulation as a consequence of prenatal
      alcohol exposure: a model for fetal alcohol spectrum disorders.
AB  - There is abundant evidence that prenatal alcohol exposure leads to a range of
      behavioral and cognitive impairments, categorized under the term fetal alcohol
      spectrum disorders (FASDs). These disorders are pervasive in Western cultures and
      represent the most common preventable source of neurodevelopmental disabilities.
      The genetic and epigenetic etiology of these phenotypes, including those factors
      that may maintain these phenotypes throughout the lifetime of an affected
      individual, has become a recent topic of investigation. This review integrates
      recent data that has progressed our understanding FASD as a continuum of
      molecular events, beginning with cellular stress response and ending with a long
      term "footprint" of epigenetic dysregulation across the genome. It reports on
      data from multiple ethanol-treatment paradigms in mouse models that identify
      changes in gene expression that occur with respect to neurodevelopmental timing
      of exposure and ethanol dose. These studies have identified patterns of genomic
      alteration that are dependent on the biological processes occurring at the time
      of ethanol exposure. This review also adds to evidence that epigenetic processes
      such as DNA methylation, histone modifications, and non-coding RNA regulation may
      underlie long-term changes to gene expression patterns. These may be initiated by
      ethanol-induced alterations to DNA and histone methylation, particularly in
      imprinted regions of the genome, affecting transcription which is further fine
      tuned by altered microRNA expression. These processes are likely complex, genome
      wide, and interrelated. The proposed model suggests a potential for intervention,
      given that epigenetic changes are malleable and may be altered by postnatal
      environment. This review accentuates the value of mouse models in deciphering the
      molecular etiology of FASD, including those processes that may provide a target
      for the ammelioration of this common yet entirely preventable disorder. 

PMID- 24917882
TI  - Genetic-based prediction of disease traits: prediction is very difficult,
      especially about the future.
AB  - Translation of results from genetic findings to inform medical practice is a
      highly anticipated goal of human genetics. The aim of this paper is to review and
      discuss the role of genetics in medically-relevant prediction. Germline genetics
      presages disease onset and therefore can contribute prognostic signals that
      augment laboratory tests and clinical features. As such, the impact of genetic
      based predictive models on clinical decisions and therapy choice could be
      profound. However, given that (i) medical traits result from a complex interplay
      between genetic and environmental factors, (ii) the underlying genetic
      architectures for susceptibility to common diseases are not well-understood, and
      (iii) replicable susceptibility alleles, in combination, account for only a
      moderate amount of disease heritability, there are substantial challenges to
      constructing and implementing genetic risk prediction models with high utility.
      In spite of these challenges, concerted progress has continued in this area with
      an ongoing accumulation of studies that identify disease predisposing genotypes.
      Several statistical approaches with the aim of predicting disease have been
      published. Here we summarize the current state of disease susceptibility mapping
      and pharmacogenetics efforts for risk prediction, describe methods used to
      construct and evaluate genetic-based predictive models, and discuss applications.

PMID- 24917883
TI  - Evolution of genomic structural variation and genomic architecture in the
      adaptive radiations of African cichlid fishes.
AB  - African cichlid fishes are an ideal system for studying explosive rates of
      speciation and the origin of diversity in adaptive radiation. Within the last few
      million years, more than 2000 species have evolved in the Great Lakes of East
      Africa, the largest adaptive radiation in vertebrates. These young species show
      spectacular diversity in their coloration, morphology and behavior. However,
      little is known about the genomic basis of this astonishing diversity. Recently,
      five African cichlid genomes were sequenced, including that of the Nile Tilapia
      (Oreochromis niloticus), a basal and only relatively moderately diversified
      lineage, and the genomes of four representative endemic species of the adaptive
      radiations, Neolamprologus brichardi, Astatotilapia burtoni, Metriaclima zebra,
      and Pundamila nyererei. Using the Tilapia genome as a reference genome, we
      generated a high-resolution genomic variation map, consisting of single
      nucleotide polymorphisms (SNPs), short insertions and deletions (indels),
      inversions and deletions. In total, around 18.8, 17.7, 17.0, and 17.0 million
      SNPs, 2.3, 2.2, 1.4, and 1.9 million indels, 262, 306, 162, and 154 inversions,
      and 3509, 2705, 2710, and 2634 deletions were inferred to have evolved in N.
      brichardi, A. burtoni, P. nyererei, and M. zebra, respectively. Many of these
      variations affected the annotated gene regions in the genome. Different patterns
      of genetic variation were detected during the adaptive radiation of African
      cichlid fishes. For SNPs, the highest rate of evolution was detected in the
      common ancestor of N. brichardi, A. burtoni, P. nyererei, and M. zebra. However,
      for the evolution of inversions and deletions, we found that the rates at the
      terminal taxa are substantially higher than the rates at the ancestral lineages.
      The high-resolution map provides an ideal opportunity to understand the genomic
      bases of the adaptive radiation of African cichlid fishes. 

PMID- 24917884
TI  - Epigenetic-based therapies for Friedreich ataxia.
AB  - Friedreich ataxia (FRDA) is a lethal autosomal recessive neurodegenerative
      disorder caused primarily by a homozygous GAA repeat expansion mutation within
      the first intron of the FXN gene, leading to inhibition of FXN transcription and
      thus reduced frataxin protein expression. Recent studies have shown that
      epigenetic marks, comprising chemical modifications of DNA and histones, are
      associated with FXN gene silencing. Such epigenetic marks can be reversed, making
      them suitable targets for epigenetic-based therapy. Furthermore, since FRDA is
      caused by insufficient, but functional, frataxin protein, epigenetic-based
      transcriptional re-activation of the FXN gene is an attractive therapeutic
      option. In this review we summarize our current understanding of the epigenetic
      basis of FXN gene silencing and we discuss current epigenetic-based FRDA
      therapeutic strategies. 

PMID- 24917885
TI  - Imaging of polysaccharides in the tomato cell wall with Raman microspectroscopy.
AB  - BACKGROUND: The primary cell wall of fruits and vegetables is a structure mainly
      composed of polysaccharides (pectins, hemicelluloses, cellulose). Polysaccharides
      are assembled into a network and linked together. It is thought that the
      percentage of components and of plant cell wall has an important influence on
      mechanical properties of fruits and vegetables. RESULTS: In this study the Raman
      microspectroscopy technique was introduced to the visualization of the
      distribution of polysaccharides in cell wall of fruit. The methodology of the
      sample preparation, the measurement using Raman microscope and multivariate image
      analysis are discussed. Single band imaging (for preliminary analysis) and
      multivariate image analysis methods (principal component analysis and
      multivariate curve resolution) were used for the identification and localization
      of the components in the primary cell wall. CONCLUSIONS: Raman microspectroscopy
      supported by multivariate image analysis methods is useful in distinguishing
      cellulose and pectins in the cell wall in tomatoes. It presents how the
      localization of biopolymers was possible with minimally prepared samples.

PMID- 24917886
TI  - A comparative study of ethanol production using dilute acid, ionic liquid and
      AFEXTM pretreated corn stover.
AB  - BACKGROUND: In a biorefinery producing cellulosic biofuels, biomass pretreatment
      will significantly influence the efficacy of enzymatic hydrolysis and microbial
      fermentation. Comparison of different biomass pretreatment techniques by studying
      the impact of pretreatment on downstream operations at industrially relevant
      conditions and performing comprehensive mass balances will help focus attention
      on necessary process improvements, and thereby help reduce the cost of biofuel
      production. RESULTS: An on-going collaboration between the three US Department of
      Energy (DOE) funded bioenergy research centers (Great Lakes Bioenergy Research
      Center (GLBRC), Joint BioEnergy Institute (JBEI) and BioEnergy Science Center
      (BESC)) has given us a unique opportunity to compare the performance of three
      pretreatment processes, notably dilute acid (DA), ionic liquid (IL) and ammonia
      fiber expansion (AFEX(TM)), using the same source of corn stover. Separate
      hydrolysis and fermentation (SHF) was carried out using various combinations of
      commercially available enzymes and engineered yeast (Saccharomyces cerevisiae
      424A) strain. The optimal commercial enzyme combination (Ctec2: Htec2: Multifect
      Pectinase, percentage total protein loading basis) was evaluated for each
      pretreatment with a microplate-based assay using milled pretreated solids at 0.2%
      glucan loading and 15 mg total protein loading/g of glucan. The best enzyme
      combinations were 67:33:0 for DA, 39:33:28 for IL and 67:17:17 for AFEX. The
      amounts of sugar (kg) (glucose: xylose: total gluco- and xylo-oligomers) per 100
      kg of untreated corn stover produced after 72 hours of 6% glucan loading
      enzymatic hydrolysis were: DA (25:2:2), IL (31:15:2) and AFEX (26:13:7).
      Additionally, the amounts of ethanol (kg) produced per 100 kg of untreated corn
      stover and the respective ethanol metabolic yield (%) achieved with exogenous
      nutrient supplemented fermentations were: DA (14.0, 92.0%), IL (21.2, 93.0%) and
      AFEX (20.5, 95.0%), respectively. The reason for lower ethanol yield for DA is
      because most of the xylose produced during the pretreatment was removed and not
      converted to ethanol during fermentation. CONCLUSIONS: Compositional analysis of
      the pretreated biomass solids showed no significant change in composition for
      AFEX treated corn stover, while about 85% of hemicellulose was solubilized after
      DA pretreatment, and about 90% of lignin was removed after IL pretreatment. As
      expected, the optimal commercial enzyme combination was different for the solids
      prepared by different pretreatment technologies. Due to loss of nutrients during
      the pretreatment and washing steps, DA and IL pretreated hydrolysates required
      exogenous nutrient supplementation to ferment glucose and xylose efficiently,
      while AFEX pretreated hydrolysate did not require nutrient supplementation.

PMID- 24917887
TI  - Anaphylatoxin C5a modulates hepatic stellate cell migration.
AB  - BACKGROUND: C5a and its cognate receptor, C5a receptor (C5aR), key elements of
      complement, are critical modulators of liver immunity and fibrosis. However, the
      molecular mechanism for the cross talk between complement and liver fibrosis is
      not well understood. C5a is a potent chemokine regulating migration of cells in
      the innate immune system. Since activation and migration of hepatic stellate
      cells (HSC) are hallmarks of liver fibrosis, we hypothesized that C5a contributes
      to fibrosis by regulating HSC activation and/or migration. RESULTS: Primary
      cultures of mouse HSC increased expression of alpha smooth muscle actin (alpha
      SMA) and collagen 1A (Col1A1) mRNA in response to activation on plastic.
      Expression of mRNA for C5aR, but not C5L2, a second C5a receptor that acts as a
      negative regulator, increased in parallel with markers of HSC activation in
      culture. Increased expression of C5aR on activated HSC was confirmed by
      immunocytochemistry. Cell surface expression of C5aR was also detected by flow
      cytometry on activated HSC isolated from mice expressing GFP under the control of
      the collagen promoter after exposure to chronic carbon tetrachloride. To
      understand the functional significance of C5aR expression in HSC, we next
      investigated whether C5a influenced HSC activation and/or migration. Challenge of
      HSC with C5a during culture had no effect on expression of alpha-SMA and Col1A1,
      suggesting that C5a did not influence HSC activation. Another important
      characteristic of HSC is their migratory capacity; migration of HSC in response
      to platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1
      (MCP-1) has been well characterized. Challenge of HSC with C5a enhanced HSC
      migration almost as efficiently as PDGF in a two-dimensional wound healing and
      Boyden chamber migration assays. C5a also stimulated expression of MCP-1. C5a
      induced cell migration was slowed, but not completely inhibited, in presence of
      227016, a MCP-1 receptor antagonist, suggesting C5a-induced migration occurs via
      both MCP-1-dependent and -independent mechanisms. CONCLUSIONS: These data reveal
      that C5a regulates migration of HSC and suggest a novel mechanism by which
      complement contributes to hepatic fibrosis. C5a and its receptors are therefore
      potential therapeutic targets for the prevention and/or treatment of liver
      fibrosis.

PMID- 24917888
TI  - Laparoscopic fertility-sparing surgery for early stage ovarian cancer: a single
      centre case series and systematic literature review.
AB  - BACKGROUND: There is as yet limited evidence about fertility-sparing surgery for
      early ovarian cancer (EOC) carried out laparoscopically. We sought to analyze
      recurrence patterns and fertility outcome in a cohort of ovarian cancer patients
      who underwent fertility-saving laparoscopic surgical staging. METHODS: We
      conducted a retrospective analysis of prospectively collected data on all
      patients undergoing fertility-sparing laparoscopic staging procedures for
      presumed EOC at a single gynecologic oncology service. Oncologic safety and
      reproductive outcome were the main outcome measures. The pertinent literature is
      reviewed. RESULTS: The study cohort consisted of 12 women. Cases included 5
      invasive epithelial tumors and 7 nonepithelial tumors. The disease was
      reclassified to a higher stage in one woman. After a median follow up period of
      38 months (range: 14-108), the overall survival was 100% and recurrence-free
      survival 90.9%. Five (100%) of patients who attempted pregnancy conceived
      spontaneously. Three of them had uneventful term pregnancy delivering healthy
      babies. The literature search yielded 62 cases of laparoscopic fertility
      conserving surgery for ovarian cancer. There were 4 (6.2%) recurrences.
      Cumulative pregnancy and live birth rate were not estimable as earlier
      publications lack essential data. CONCLUSIONS: Laparoscopic staging may represent
      a viable option for premenopausal women seeking fertility preservation in the
      setting of early ovarian cancer. More research is needed to determine whether
      laparoscopy may offer reproductive benefits to this particular population.

PMID- 24917889
TI  - The effect on fall rate of blood glucose testing at the time of falls in elderly
      diabetics.
AB  - OBJECTIVE: To determine the pattern of blood sugar and HbA1c testing among
      supportive living residents with diabetes and whether, in those with diabetes,
      blood glucose measurement was done at the time of a fall. RESEARCH DESIGN AND
      METHODS: The management of diabetes in relation to falls in the supportive living
      sector is unknown. A cross-sectional questionnaire study in Edmonton Alberta,
      Canada of Designated Supportive Living (DSL) homes have places funded by Alberta
      Health Services and other homes (SL) that have no funded places. A questionnaire
      was distributed to Directors of Care/managers of supportive living homes, with
      telephone interview follow-up if required. RESULTS: Sixty responses from 61 of
      the 71 homes (86%) provided information. 21 were DSL and 39 were SL homes. DSL
      homes were significantly more likely than SL ones to report that residents with
      diabetes had blood glucose measurements as part of regular care, to be aware that
      glycosylated haemoglobin was measured, and to say that blood glucose was measured
      at the time of a fall. Regression analysis identified that facilities with a
      policy to measure blood glucose at the time of a fall had a lower rate of falls
      in residents with diabetes than facilities without such a policy (p < 0.05). No
      effect of this policy was seen in residents without diabetes. CONCLUSION:
      Residents with diabetes were less likely to fall in homes that indicated that
      they had a policy to measure blood glucose at the time of a fall.

PMID- 24917890
TI  - Efficacy and safety of vildagliptin, Saxagliptin or Sitagliptin as add-on therapy
      in Chinese patients with type 2 diabetes inadequately controlled with dual
      combination of traditional oral hypoglycemic agents.
AB  - BACKGROUND: The oral DPP-4 inhibitors are new incretin-based therapies for
      treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4
      inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual
      combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes
      patients. METHODS: In this 24-week, randomized, open-label, parallel clinical
      trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c]
      >=7.5% to <=10%) patients with type 2 diabetes, who were treated by dual
      combination of metformin and another traditional oral hypoglycemic agent
      (glimepiride, acarbose or pioglitazone). 207 patients had been randomized to add
      on 5 mg saxagliptin group or 100 mg sitagliptin once daily group, or 50 mg
      vildagliptin twice daily group for 24 weeks. HbA1c, fasting and postprandial
      blood glucose (FBG and P2hBG), body weight, body mass index (BMI), episodes of
      hypoglycemia and adverse events were evaluated. RESULT: After 24 weeks, HbA1c,
      FBG, and P2hBG of each group were significantly decreased. (saxagliptin vs
      vildagliptin vs sitagliptin: HbA1c: -1.2% vs -1.3% vs -1.1%; FBG: -1.8 mmol/l vs 
      2.4 mmol/l vs -1.5 mmol/l; P2hBG: -3.4 mmol/l vs -3.7 mmol/l vs -3.2 mmol/l). The
      changes of HbA1c and P2hBG among the three groups had no significance. However,
      vildagliptin-added group showed the greatest reduction (p < 0.001), while,
      sitagliptin-added group showed the lowest reduction (p < 0.001) in terms of FPG
      changes. Proportions of patients achieving HbA1c < 7% at the end were similar in
      three groups (saxagliptin 59%, vildagliptin 65%, sitagliptin 59%). Mild
      hypoglycemia was commonly reported among the three groups (saxagliptin 6%,
      vildagliptin 2%, sitagliptin 3%). No significant between-group difference was
      shown in other AEs. CONCLUSION: The three gliptins showed almost similar glycemic
      control and incidence of adverse events. However, for FBG control, saxagliptin
      demonstrated superiority to sitagliptin, while, inferiority to vildagliptin.

PMID- 24917891
TI  - 3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND
      FASTING CONDITIONS.
AB  - The heart requires continuous ATP availability that is generated in the
      mitochondria. Although studies using the cell culture and perfused organ models
      have been carried out to investigate the biochemistry in the mitochondria in
      response to a change in substrate supply, mitochondrial bioenergetics of heart
      under normal feed or fasting conditions has not been studied at the tissue level
      with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of
      many food-derived metabolites to generate ATP in the mitochondria is realized
      through the NADH/NAD+ couple acting as a central electron carrier. We employed
      the Chance redox scanner - the low-temperature fluorescence scanner to image the
      three-dimensional (3D) spatial distribution of the mitochondrial redox states in
      heart tissues of rats under normal feeding or an overnight starvation for 14.5 h.
      Multiple consecutive sections of each heart were imaged to map three redox
      indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine
      dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the
      micro-heterogeneity and the spatial distribution of these redox indices. The
      quantitative analysis showed that in the fasted hearts the standard deviation of
      both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value
      of 0.032 and 0.045, respectively, indicating that the hearts become relatively
      more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p =
      0.038). No significant change in Fp was found (p = 0.4). The NADH/Fp ratio
      decreased with a marginal p value (0.076). The decreased NADH in the fasted
      hearts is consistent with the cardiac cells' reliance of fatty acids consumption
      for energy metabolism when glucose becomes scarce. The experimental observation
      of NADH decrease induced by dietary restriction in the heart at tissue level has
      not been reported to our best knowledge. The Chance redox scanner demonstrated
      the feasibility of 3D imaging of the mitochondrial redox state in the heart and
      provides a useful tool to study heart metabolism and function under normal,
      dietary-change and pathological conditions at tissue level.

PMID- 24917892
TI  - Is there any relation between chronic cerebrospinal venous insufficiency and
      multiple sclerosis? - a critical review.
AB  - Summary Though the etiology of multiple sclerosis remains unknown, the widely
      accepted explanation is that it has an autoimmune inflammatory background. In
      2006 Paolo Zamboni renewed the somewhat forgotten vascular theory of the
      pathogenesis of multiple sclerosis, proposing the new entity of 'chronic
      cerebrospinal venous insufficiency'. As a result of this hypothesis, Zamboni
      suggested an endovascular treatment for multiple sclerosis involving venoplasty
      of the internal jugular vein and the azygos vein. Unfortunately, several teams
      have tried to replicate Zamboni's results without success. In this review, we
      present a chronological description of the results of the studies conducted by
      Zamboni and the later attempts to replicate his work. The main conclusion is
      that, taking into account results that are currently available, we should remain
      cautious and routine use of this treatment in patients should not be advisable. 

PMID- 24917893
TI  - A Previously Discounted Flap Now Reconsidered: MatriDerm and Split-Thickness Skin
      Grafting for Tendon Cover Following Dorsalis Pedis Fasciocutaneous Flap in Lower
      Limb Trauma.
AB  - OBJECTIVE: The dorsalis pedis flap has reliable vascularity; however, its use is
      limited by reports of donor site morbidity including infection, delayed healing,
      exposure of tendons, and later contractures. The purpose of this study was to
      demonstrate its continued role in lower limb trauma when the donor site is
      reconstructed with MatriDerm to avoid complications. METHODS: A 65-year-old man
      presented with a displaced, Gustilo 3b open transverse fracture of his left
      distal fibula. He had a 2 cm(2) open wound over his lateral malleolus. RESULTS:
      Following review of possible local options, a dorsalis pedis fasciocutaneous flap
      was deemed best for coverage, and the donor site was closed with 1-mm MatriDerm
      dermal matrix and a 6/1000 inch split-thickness skin graft (STSG) in a single
      stage. Three months postoperatively, the foot had excellent function and
      cosmesis, with toes in a neutral position and a full range of movement.
      CONCLUSIONS: The dorsalis pedis flap is a valuable reconstructive option for
      defects of the foot and ankle. Its major limitation donor site morbidity can be
      overcome by the additional application of a dermal substitute such as MatriDerm
      under the STSG.

PMID- 24917894
TI  - Application of the Single Use Negative Pressure Wound Therapy Device (PICO) on a
      Heterogeneous Group of Surgical and Traumatic Wounds.
AB  - OBJECTIVES: Traumatic wounds and surgery inherently have their complications.
      Localized infections, wound dehiscence, and excessive wound leakage can be
      devastating to the patient with a prolonged recovery, but it is also costly to
      the hospital with an increased length of stay, extra workload, and dressing
      changes. The single use PICO (Smith and Nephew Healthcare, Hull, United Kingdom)
      negative pressure wound therapy (NPWT) dressing has revolutionized our management
      of various acute, chronic, and high output wounds. It requires fewer dressing
      changes than conventional practice, is used in the outpatient setting, and is a
      necessary adjuvant therapy to hasten wound healing. AIMS: To observe the efficacy
      of the PICO vacuum-assisted healing within a cost improvement programme.
      SETTINGS: Plastic surgery department, Royal London Hospital. MATERIALS AND
      METHODS: Twenty-one patients with a diversity of postoperative or posttraumatic
      wounds were considered suitable for PICO application and treated totally on an
      outpatient basis once the PICO dressing was applied. All wounds were then
      subjected to continued PICO dressings until healed. RESULTS: All patients
      tolerated the PICO well with no dressing failure or failure to comply. The number
      of dressings per patient ranged from 1 to 7. The cost per patient of treatment
      ranged from L120 to L1578. Estimated cost of all PICO dressing for 21 patients
      including plastic surgery dressing clinic appointments = L13,345. Median length
      of treatment to healing (days) = 16; standard deviation = 9.5. Eight patients
      would have had an inpatient bed stay with conventional therapy, total 24 bed days
      saved at Bartshealth @L325 per day. CONCLUSIONS: The outpatient application of a
      disposable NPWT can benefit a wide range of clinical wounds that optimizes
      patient care, promotes rapid wound healing, and importantly helps manage costs.

PMID- 24917895
TI  - Forearm compartment syndrome.

PMID- 24917896
TI  - Maffucci syndrome.

PMID- 24917897
TI  - Morel-lavallee lesion.

PMID- 24917898
TI  - Making contact.

PMID- 24917899
TI  - Catch 22, giant congenital melanocytic nevus in a florid keloid former.

PMID- 24917900
TI  - Necrotizing fasciitis.

PMID- 24917901
TI  - Reconstruction for the distal urethral end incorrectly anastomosed to the
      proximal false passage in the treatment of urethral stricture.
AB  - PATIENT: Male, 24 FINAL DIAGNOSIS: Urethral stricture Symptoms: - MEDICATION: -
      Clinical Procedure: - Specialty: Urology. OBJECTIVE: Unusual or unexpected effect
      of treatment. BACKGROUND: The most dependable management of anterior urethral
      stricture is the complete excision of the area of fibrosis, with a primary
      reanastomosis of the normal ends of the anterior urethra. CASE REPORT: A 24-year
      old man had urethral stricture in the penoscrotal junction caused by
      catheterization approximately 3 years ago. After the resection of the urethral
      stricture segment and the end-to-end anastomosis were performed, in addition to
      stricture, urethrocutaneous fistula formation as another complication in the
      penoscrotal junction was confirmed. The direct vision internal urethrotomy did
      not improve all the above symptoms. The retrograde urethrogram and voiding cysto
      urethrogram showed complete obliteration in the penile urethra, urethrocutaneous
      fistula, and proximal urethral bifurcation singularity. Intraoperatively, we
      found that the distal urethral end had been anastomosed to the proximal false
      passage in the initial surgery and the proximal urethra was located in the dorsal
      side of the false passage. Then, tubularized preputial flap urethroplasty was
      performed. The patient was followed up for 10 months. His peak urinary flow was
      18.3 milliliter per second. CONCLUSIONS: We would remind urologists that urethral
      end intraoperatively anastomosed to the false passage is a rare, serious,
      avoidable, and elementary medical error. Urethroplasty is one of the curative
      choices for treatment of this unexpected condition.

PMID- 24917902
TI  - Changing patterns of bacterial strains in adults and children with otitis media
      in korean tertiary care centers.
AB  - OBJECTIVES: Otitis media (OM) is an infectious disease that affects all age
      brackets. Aural discharge is a typical symptom, occurring in all subtypes of OM.
      We have compared the identity and antibiotic sensitivity of bacteria isolated
      from aural discharges of adults and children with various types of OM, including
      acute OM (AOM), OM with effusion (OME), chronic OM (COM), and cholesteatomatous
      OM (CSOM). METHODS: The study involved 2,833 patients who visited five tertiary
      hospitals between January 2001 and December 2010 and were diagnosed with AOM,
      OME, COM, or CSOM. The patients were divided into a pediatric group and an adult
      group, and the distribution of cultured bacteria and their antibiotic sensitivity
      were compared in the two groups. RESULTS: Bacterial detection rates were higher
      in adults than in children with OME and COM (P=0.000 each). The majority of the
      bacteria cultured from patients with AOM and OME bacteria were methicillin
      susceptible Staphylococcus aureus (MSSA) and Streptococcus pneumoniae. Bacteria
      cultured from children were more susceptible to antibiotics (P=0.002) and had
      higher antibiotic sensitivity (P=0.001) than were bacteria cultured from adults.
      The majority of bacteria culture from patients with COM and CSOM were MSSA and
      pathogenic Pseudomonas aeruginosa. The frequency of methicillin-resistant
      Staphylococcus aureus was significantly higher in adults than in children, and
      more strains of bacteria isolated from adults were sensitive to the antibiotics
      septrin, vancomycin, and teicoplanin. CONCLUSION: Bacteria cultured from children
      were more susceptible to antibiotics and had higher antibiotic sensitivity than
      did bacteria cultured from adults.

PMID- 24917903
TI  - Effect of different sounds on the treatment outcome of tinnitus retraining
      therapy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the therapeutic effect of
      three different types of sounds on tinnitus patients undergoing tinnitus
      retraining therapy (TRT). METHODS: This is a single-institution retrospective
      study, performed in one tertiary otological referral center. Thirty-eight adults
      with subjective idiopathic tinnitus who were followed for at least 9 weeks were
      enrolled. Sound therapy was delivered in 3 different ways: narrowband noise TRT
      (nTRT); mixed band noise TRT (mTRT); broadband noise TRT (bTRT). Treatment
      response was measured through validated psychometric questionnaires: Tinnitus
      Handicap Inventory (THI), visual analog scale (VAS) on annoyance, and numerical
      description of hours of tinnitus perception (awareness hours). RESULTS: A total
      of 38 patients were followed for at least 9 weeks. In nTRT group, all outcome
      measures including THI, VAS, and the awareness hours, decreased over 9 weeks with
      no statistical significance. In mTRT group, all outcome measures except for
      awareness hours significantly improved 9 weeks after the beginning of the
      treatment. In bTRT group, all outcome measures decreased significantly in 9
      weeks. When therapeutic success is defined as improvement in THI 7 or more, bTRT
      group (77.8%) showed a higher success rate than other groups for 38 patients with
      the minimum follow-up of 9 weeks. CONCLUSION: All three sounds can provide relief
      in patients with annoying tinnitus after TRT. However, there is difference in the
      therapeutic effect according to sound types. Broadband sound seems to be better
      than narrowband sound or mixed sound in relieving the patients from tinnitus.
      Therefore, sound therapy with broadband noise may be more appropriate during TRT,
      but further evidence is needed for precise conclusion.

PMID- 24917904
TI  - Advantages of binaural amplification to acceptable noise level of directional
      hearing aid users.
AB  - OBJECTIVES: The goal of the present study was to examine whether Acceptable Noise
      Levels (ANLs) would be lower (greater acceptance of noise) in binaural listening
      than in monaural listening condition and also whether meaningfulness of
      background speech noise would affect ANLs for directional microphone hearing aid
      users. In addition, any relationships between the individual binaural benefits on
      ANLs and the individuals' demographic information were investigated. METHODS:
      Fourteen hearing aid users (mean age, 64 years) participated for experimental
      testing. For the ANL calculation, listeners' most comfortable listening levels
      and background noise level were measured. Using Korean ANL material, ANLs of all
      participants were evaluated under monaural and binaural amplification with a
      counterbalanced order. The ANLs were also compared across five types of competing
      speech noises, consisting of 1- through 8-talker background speech maskers. Seven
      young normal-hearing listeners (mean age, 27 years) participated for the same
      measurements as a pilot testing. RESULTS: The results demonstrated that
      directional hearing aid users accepted more noise (lower ANLs) with binaural
      amplification than with monaural amplification, regardless of the type of
      competing speech. When the background speech noise became more meaningful,
      hearing-impaired listeners accepted less amount of noise (higher ANLs), revealing
      that ANL is dependent on the intelligibility of the competing speech. The
      individuals' binaural advantages in ANLs were significantly greater for the
      listeners with longer experience of hearing aids, yet not related to their age or
      hearing thresholds. CONCLUSION: Binaural directional microphone processing
      allowed hearing aid users to accept a greater amount of background noise, which
      may in turn improve listeners' hearing aid success. Informational masking
      substantially influenced background noise acceptance. Given a significant
      association between ANLs and duration of hearing aid usage, ANL measurement can
      be useful for clinical counseling of binaural hearing aid candidates or
      unsuccessful users.

PMID- 24917905
TI  - The efficacy of preemptive analgesia with pregabalin in septoplasty.
AB  - OBJECTIVES: Pregabalin is used to treat neuropathic pain and has shown analgesic
      properties in postoperative pain. The aim of this study was to investigate the
      effectiveness and safety of pregabalin in reducing postoperative pain in patients
      after septoplasty. METHODS: Forty-seven patients scheduled for elective
      septoplasty were randomly assigned to groups that received either pregabalin (150
      mg) or placebo, both one hour before surgery and 12 hours after the initial dose.
      Pain (verbal numerical rating scale, VNRS) and side effect assessments were
      performed at 6, 12, 12 to 24, and 24 to 48 hours postoperatively. RESULTS: From 1
      to 12 hours postoperatively, VNRS scores for pain were lower in the pregabalin
      group (n=24) than in the placebo group (n=23; P<0.05). The number of patients who
      needed rescue analgesics was lower in the pregabalin group (P=0.042). The
      incidence of nausea and vomiting did not differ between groups (P=0.666), and the
      incidence of sedation was higher in the placebo groups (P=0.022). CONCLUSION: The
      perioperative administration of oral pregabalin (150 mg twice) is an effective
      and safe way to reduce early postoperative pain in patients undergoing
      septoplasty.

PMID- 24917906
TI  - Effects of topical intranasal doxycycline treatment in the rat allergic rhinitis
      model.
AB  - OBJECTIVES: Allergic rhinitis (AR) is a chronic upper respiratory tract disease
      that inflames the mucous membranes of the nose and occurs when circulating
      inflammatory cells including eosinophils and basophils migrate to and accumulate
      in the inflammation area by passing through the interstitium and capillary walls.
      To pass through these barriers, the inflammatory cells degrade extracellular
      matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells
      mediate the degradation of these proteins. MMPs have synthetic inhibitors and
      doxycycline, a tetracycline antibiotic, inhibits MMPs. This study investigated
      the efficiency of intranasal doxycycline in decreasing the symptoms and
      inflammatory cell infiltration in an animal model of AR. METHODS: AR was created
      in female Wistar rats by repeated intranasal challenge with ovalbumin by
      intraperitoneal injection. For 15 days, topical intranasal doxycycline was
      administered one hour before ovalbumin administration. Following intranasal
      administration, nasal symptoms were scored and the nasal mucosae of all rats were
      evaluated histopathologically. To investigate tissue changes, hematoxyline-eosin
      and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss,
      goblet cell changes, vascular congestion, vascular proliferation, inflammatory
      cell infiltration, eosinophil infiltration and the degree of hypertrophy in
      chondrocytes were evaluated with light microscopy. RESULTS: Typical symptoms of
      AR were decreased by intranasal doxycycline administration. These effects were
      stable after repeated intranasal ovalbumin administration. Histological
      evaluation of doxycycline treated rats did not reveal typical inflammatory
      changes associated with AR. CONCLUSION: MMPs may have crucial functions in AR and
      topical intranasal doxycycline, which decreases inflammatory cell infiltration,
      may offer an alternative therapy for AR.

PMID- 24917907
TI  - Dexamethasone Induces Apoptosis of Nasal Polyp-Derived Tissue Cultures Through
      JNK and p38 MAPK Activation.
AB  - OBJECTIVES: Glucocorticoids, such as dexamethasone (DEX), increase apoptosis in a
      variety of white cells in nasal polyps and apoptosis is an important factor in
      the resolution of inflammation. However, the mechanism of glucocorticoids induced
      apoptosis in nasal polyp remains unclear. In this study the authors evaluated
      which pathways were engaged in apoptosis induced by DEX in an ex vivo model of
      nasal polyps. METHODS: Nasal polyp tissues were cultured using an air-liquid
      interface method. Cultures were maintained in the absence or presence of DEX (10
      or 100 uM) for 24 hours. To investigate the involvement of the apoptotic
      signaling pathways in nasal polyp, such as caspase cascades, Fas-FasL signaling
      pathway, mitochondrial pathway and p38 mitogen-activated protein kinase
      (MAPK)/JNK pathway, the authors performed reverse transcription-polymerase chain
      reaction and Western blotting. RESULTS: The expression ratios of FasL, activated
      form of caspase-8, caspase-9, and caspase-3 were significantly higher in DEX
      treated polyps (P<0.01). In the Bcl-2 family expression, the anti-apoptotic
      molecules, Bcl-2 and Bcl-XL decreased, but pro-apoptotic molecules, Bax
      increased, and Bid and Bad were activated. In the conventional MAPKs, JNK, and
      the phospho-p38 MAPK were significantly higher, but phospho-extracellular signal
      regulated kinase (ERK)1/2 was significantly lower in DEX-treated polyps (P<0.01).
      CONCLUSION: DEX induces apoptosis of nasal polyp via caspase cascades, Fas-FasL
      signaling pathway, mitochondrial pathway and p38 MAPK/JNK pathway.

PMID- 24917908
TI  - Partial Superficial Parotidectomy via Retroauricular Hairline Incision.
AB  - OBJECTIVES: The purpose of this study was to evaluate the usefulness of
      retroauricular hair line incision (RAHI) in partial superficial parotidectomy by
      comparison with modified Blair incision or facelift incision. METHODS: Medical
      records of 73 patients with benign parotid tumor who underwent partial
      superficial parotidectomy were retrospectively reviewed. Size and location of
      tumors, operative time, occurrence of facial nerve paralysis and Frey's syndrome,
      and cosmetic outcomes were compared among RAHI, facelift incision (FLI), modified
      Blair incision (MBI) groups. RESULTS: RAHI group showed better cosmetic results
      than FLI group or MBI group compared with other type of incisions (P<0.001,
      P<0.001, respectively). Among the 3 groups, there were no significant differences
      of operative time and location of tumor (P=0.377), size of tumor (P>0.999),
      occurrence of temporary or permanent facial nerve paralysis (P=0.745) and Frey's
      syndrome (P=0.940). CONCLUSION: Partial superficial parotidectomy can be done
      safely by RAHI in most cases of benign parotid tumor. Compared with MBI or FLI,
      RAHI has better cosmetic outcome with no increase of operative time or
      postoperative complications.

PMID- 24917909
TI  - The Role of Transnasal Esophagoscopy in ENT Office: A Prospective, Multicenter
      Study in Korea.
AB  - OBJECTIVES: The purpose of study was to report the current role of transnasal
      esophagoscopy (TNE) in Korea. METHODS: One hundred thirty-seven patients who
      underwent TNE at Soonchunhyang University Bucheon Hospital (n=69) and Korea
      University Anam Hospital (n=68) from July 2007 to February 2009 were
      prospectively analyzed. Laryngopharyngeal reflux disease (LPRD) patients without
      any response to proton-pump inhibitor (n=102), and patients with complaints that
      require esophagoscopy as part of their evaluation (n=35) were included in this
      study; investigation of metachronous lesions or routine follow-up screening of
      head and neck cancer patients, n=17; dysphagia, n=9; blood tinged saliva, n=4; to
      determine the cause of vocal fold paralysis as screening tool, n=4; suspicious
      esophageal foreign body, n=1. RESULTS: Fifty-three patients (38.7%) had positive
      findings on TNE. Positive finding ratio was highest in group of dysphagia (7
      among 9 patients, 78%). Forty-two patients (41.1%) were found to have pathology
      (esophagitis, n=41; esophageal diverticulum, n=1) during the screening
      examination for LPRD. There were no significant complications in any of the
      patients. CONCLUSION: TNE is a high-yield diagnostic and therapeutic modality
      available to otolaryngologists for use on awake patients in the office setting.

PMID- 24917910
TI  - Clinical history, prognostic factors, and management of facial nerve in malignant
      tumors of the parotid gland.
AB  - OBJECTIVES: We analyzed the outcomes following clinical management of parotid
      masses that were determined to be malignant tumors after parotidectomy. METHODS:
      We evaluated data from 70 patients with parotid malignancies between November
      1994 and December 2005. RESULTS: Among salivary histotypes (n=49), the most
      significant prognostic parameter was cT4 stage at diagnosis (P=0.0055, log-rank)
      both for clinical involvement of the facial nerve and for invasion of other
      structures. The main cause of cancer-related death was a distant metastasis.
      CONCLUSION: The present series confirms that the main prognostic parameter in
      salivary parotid malignancies was cT4 classification at diagnosis, often due to
      clinical involvement of the facial nerve. The oncological outcome of salivary
      malignancies was influenced by distant metastasis more than most other head and
      neck sites. We recommend dissecting and preserving the functioning VIIth cranial
      nerve during surgery for parotid malignancies.

PMID- 24917911
TI  - Characteristics of deep neck infection in children according to weight
      percentile.
AB  - OBJECTIVES: To evaluate the effect of weight percentile on deep neck infections
      in children. METHODS: A retrospective evaluation of 79 patients who were treated
      for deep neck infections. The patients were divided into six groups according to
      weight percentile. Patients who had systemic and/or congenital disease were
      excluded. Their demographics, etiology, localization, laboratory, and treatment
      results were reviewed. RESULTS: In total, 79 pediatric patients were recorded:
      48.1% were females and 51.9% were males, with a mean age of 7.3 years. In total,
      60 patients were under the 50th percentile according to their weight versus all
      children. The anteroposterior triangle (29.1%) and submandibular (26.5%) spaces
      were most commonly involved with deep neck infection. However, the
      anteroposterior triangle space was the highest in the group below the 3rd
      percentile (44.4%). In the blood analysis, white blood cell levels in patients
      with at percentile values of 75-50 were higher than other groups (P<0.05).
      Significant differences were found between C-reactive protein and hemoglobin
      levels and diameter of abscesses. The need for surgical drainage in patients in
      lower percentiles was higher. The patients who needed surgical drainage consisted
      of 56 patients (93.3%) below the 50th percentile and 9 patients (100%) below the
      3rd percentile. CONCLUSION: Deep neck infection is more insidious and dangerous
      in low-weight-percentile children, especially those having low white blood cell
      counts, low hemoglobin levels, and high C-reactive protein in laboratory results.

PMID- 24917912
TI  - Persistent Direction-Fixed Nystagmus Following Canalith Repositioning Maneuver
      for Horizontal Canal BPPV: A Case of Canalith Jam.
AB  - The authors report a 64-year-old man who developed persistent direction fixed
      nystagmus after a canalith repositioning maneuver for horizontal canal benign
      paroxysmal positional vertigo (HC-BPPV). The patient was initially diagnosed with
      right HC-BPPV given that the Dix-Hallpike test showed geotropic horizontal
      nystagmus that was more pronounced on the right side, although the roll test did
      not show any positional nystagmus. The patient was treated with a canalith
      repositioning maneuver (Lempert maneuver). The next day, the patient experienced
      a different character of dizziness, and left-beating spontaneous nystagmus
      regardless of head position was observed. After a forced prolonged left decubitus
      and frequent head shaking, his symptoms and nystagmus resolved. This condition,
      referred to as canalith jam, can be a complication after the repositioning
      maneuver in patients with BPPV. Atypical positional tests suggest that abnormal
      canal anatomy could be the underlying cause of canalith jam. 

PMID- 24917913
TI  - Reconstruction of a columellar defect with a nasolabial island flap.
AB  - Columellar skin defects may be caused by excision of cutaneous malignancy,
      trauma, or tissue necrosis associated with surgery. Although columellar skin
      necrosis rarely occurs following rhinoplasty, this condition might be more common
      when using an external approach than a closed approach. Columellar skin incision
      performed with exaggerated tip augmentation may cause columellar necrosis. The
      nasolabial island flap, used unilaterally to cover columellar skin defects, is
      used for a single-stage reconstruction procedure and is generally not associated
      with the need for secondary surgeries. This technique is well suited for
      repairing columellar skin defects. We experienced a patient with columellar skin
      necrosis occurring after rhinoplasty which was reconstructed using a unilateral
      single-stage nasolabial island flap. 

PMID- 24917914
TI  - Sinonasal glomangiopericytoma causing oncogenic osteomalacia.
AB  - A 60-year-old woman suffered from recurrent femur neck fracture. Laboratory data
      showed serum hypophosphatemia, elevated alkaline phosphatase, normal serum
      calcium levels, and normal parathyroid hormone levels. Radiological examinations
      revealed a tumor in the right maxillary alveolar bone. The nasal cavity mass was
      removed, and the histological features were those of glomangiopericytoma. After
      removal of the tumor, some of the laboratory data normalized. Based on the
      clinical features, histopathological diagnosis and postoperative course of
      events, a diagnosis of glomangiopericytoma causing oncogenic osteomalacia was
      confirmed. We report a case of oncogenic osteomalacia caused by sinonasal
      glomangiopericytoma. 

PMID- 24917915
TI  - Oncocytic sialolipoma of the submandibular gland.
AB  - Sialolipoma, a rare tumor of the salivary gland, is a recently described variant
      of salivary gland lipoma. Oncocytic sialolipoma was first described by Pusiol et
      al. in 2009. We report the case of an oncocytic sialolipoma of the submandibular
      gland in a 43-year-old female. Excision of the tumor was performed with
      preservation of the submandibular gland. The tumor had a thin, fibrous capsule
      and consisted of abundant adipose tissue, an oncocytic nodule, and scattered
      normal glandular structures surrounded by adipose tissue. Four cases of
      sialolipoma of the submandibular gland, including the present case, were
      reviewed. All 4 tumors were developed on the right submandibular glands, with a
      composition of adipose tissue as high as that of sialolipoma of the parotid
      gland; in contrast to previous reports, three cases were in females. As newly
      described tumor type, care should be taken to distinguish oncocytic sialolipoma
      from other salivary gland neoplasms such as simple lipoma, pleomorphic adenoma,
      or oncocytoma. 

PMID- 24917916
TI  - A cervical vagal schwannoma mimicking a parathyroid cyst.
AB  - Cervical vagal schwannomas with cystic degeneration changes are extremely rare.
      These tumors are typically benign and slow growing. A 44-year-old woman underwent
      complete resection of a tumor measuring 4*3.5 cm in the right neck using the
      endoscopic approach, instead of the conventional transcervical approach. We
      applied the new scarless neck surgery technique with an endoscopic unilateral
      axillo-breast approach. The tumor originated from the right vagus nerve, and was
      confirmed to be a vagal schwannoma pathologically. The patient has been followed
      up for 18 months postoperatively with no evidence of tumor recurrence or
      neurological deficit. We report an extremely rare vagal schwannoma with cystic
      degeneration that was removed by an endoscopic approach, along with a review of
      the relevant literature. 

PMID- 24917917
TI  - Effect of Fibroblast Co-culture on In Vitro Maturation and Fertilization of Mouse
      Preantral Follicles.
AB  - BACKGROUND: The aim of this study was to evaluate fibroblast co-culture on in
      vitro maturation and fertilization of prepubertal mouse preantral follicles.
      MATERIALS AND METHODS: The ovaries of 12-14 day old mice were dissected and 120
      150 MUm intact preantral follicles with one or two layers of granulosa cells, and
      round oocytes were cultured individually in alpha-minimal essential medium (alpha
      MEM) supplemented with 5% fetal bovine serum (FBS), 100 mIU/ml recombinant
      follicle stimulating hormone, 1% insulin, transferrin, selenium mix, 100 MUg/ml
      penicillin and 50 MUg/ml streptomycin as base medium for 12 days. A total number
      of 226 follicules were cultured under two conditions: i) base medium as control
      group (n=113); ii) base medium co-cultured with mouse embryonic fibroblast (MEF)
      (n=113). Follicular diameters, alone, in addition to other factors were analyzed
      by student's t-test and chi-square test, respectively. RESULTS: The co-culture
      group showed significant differences (p<0.05) in growth rate (days 4, 6 and 8 of
      the culture period) and survival rate. However, there was no significant
      difference in antrum formation, ovulation rate and embryonic development of
      released oocytes. There were significant differences (p<0.05) in the estradiol
      and progesterone secretion at all days between the co-culture and control groups.
      CONCLUSION: Fibroblast co-culture increased survival rate and steroid production
      of preantral follicles by promoting granulosa cell proliferation.

PMID- 24917918
TI  - Does Adding Dexamethasone to Clomiphene Citrate Improve Ovulation in PCOS
      Patients? A Triple - Blind Randomized Clinical Trial Study.
AB  - BACKGROUND: A common cause of anovulation is polycystic ovarian syndrome (PCOS).
      Clomiphene citrate (CC) is the first line of treatment in PCOS patients however
      approximately 25% of patients may be CC-resistant. This study aimed to evaluate
      the efficacy of adding dexamethasone (dex) to CC in CC-resistant PCOS patients
      with the intent to improve ovulation. MATERIALS AND METHODS: This randomized
      controlled trial study was performed on 60 infertile PCOS patients referred to
      our infertility research center from 2007 to 2009. Patients were randomly divided
      in two groups and stimulation performed with dex+CC or CC+placebo. Rates of
      ovulation, pregnancy and number of mature follicles were evaluated. RESULTS:
      Ovulation rate in the dex+CC group was 21 out of 30 (70%) and in the CC+placebo
      group it was 17 out of 30 (56.7%). The pregnancy rate was 5 (16.7%) in the dex+CC
      group and 3 (10%) in the CC+placebo group. There was no significant difference
      between rates of ovulation and pregnancy in both groups, but the number of
      follicles >=18 mm were significant in the dex+CC group (p<0.05). CONCLUSION: Our
      results showed that addition of dex to cc significantly increased the number of
      matured follicles, however the ovulation and pregnancy rates were comparable
      between the two groups (Registeration Number: IRCT 138807041760 N2).

PMID- 24917919
TI  - The effects of lead acetate on sexual behavior and the level of testosterone in
      adult male rats.
AB  - BACKGROUND: In the present study, the oral effect of lead acetate on the
      parameters related to sexual behavior as well as changes in the level of
      testosterone hormone in adult male rats have been investigated. MATERIALS AND
      METHODS: Forty adult male Wistar rats were allocated into five equal groups. The
      control group received nothing, the sham group received distilled water and the
      experimental groups received 25, 50 and 100mg/kg lead acetate orally,
      respectively for 28 days. The changes in testosterone hormone level and following
      sexual behavior parameters were investigated: mount latency (ML), intromission
      latency (IL), post ejaculatory interval (PEI), mount frequency (MF), ejaculatory
      latency (EL), intromission frequency (IF), copulatory efficacy (CE) and
      intercopulatory interval (ICI). RESULTS: The levels of testosterone hormone in
      the groups that received 50 and 100 mg/kg lead acetate showed significant
      decreases in compared to the control group. Additionally, the same doses of lead
      acetate caused significant increases in ML, IL, PEI and EL compared to the
      control group. No significant change was observed in MF, but a significant
      decrease was detected in IF and CE in the experimental group that received 100
      mg/kg lead acetate when compared with the control group. ICI showed significant
      decreases in the experimental groups that received 50 and 100 mg/kg lead acetate
      compared to the control group. CONCLUSION: It can be concluded that ingestion of
      lead acetate affects some behavioral activities and the testosterone level of
      male rats. These effects might be conducted via the alteration of leydig cells
      following lead acetate poisoning.

PMID- 24917920
TI  - Effect of Culture System on Developmental Competence, Cryosurvival and DNA
      Fragmentation of In Vitro Bovine Blastocysts.
AB  - BACKGROUND: This study investigated the effect of two in vitro embryo culture
      systems (co-culture system versus cell-free sequential-media) on developmental
      competence, cryosurvival and DNA- fragmentation of in vitro developed bovine
      blastocysts. MATERIALS AND METHODS: Bovine presumptive zygotes were cultured in
      Menezo's B2 (B2) plus vero-cells or sequential synthetic oviductal fluid (SOF)
      for eight days. Subsequently, half of the expanded blastocysts developed in both
      groups were vitrified, warmed within 30 minutes and post- warming embryos along
      with their corresponding non-vitrified embryos were cultured for two additional
      days in the same medium used before vitrification. Embryo development,
      cryosurvival and apoptosis were compared between the groups. RESULTS: For non
      vitrified embryos, culture in SOF significantly promoted the potency of embryos
      to develop into blastocysts compared with the co-culture system. The difference
      in post vitrification survival rate of SOF blastocysts (83.3%) was insignificant
      compared with co-culture (84.3%). However, while total cell number of warmed
      blastocysts in the co-culture system was significantly higher in the co-culture
      versus the sequential system (215.4 vs. 170.4), the quality of survived embryos
      in terms of hatching ability and apoptosis was adversely affected by co-culture
      compared with SOF (65.0% vs. 74.3%, and 13.5% vs. 10.0%, respectively; p<0.05).
      CONCLUSION: Although co-culture system may increase the viability of embryos
      following cryopreservation, the potency and dynamics of blastocyst formation
      significantly increased with sequential media compared to the co-culture system
      which can compensate for the lower efficiency of sequential media for
      vitrification/warming purposes.

PMID- 24917921
TI  - Follicular Viability and Histological Alterations after Auto-transplantation of
      Dog Ovaries by Experimentally Inducing Blood Sinus on Stomach.
AB  - BACKGROUND: Currently, chemotherapy and radiotherapy are considered most
      effective methods for cancer treatment, however these strategies often result in
      fertility problems. A favorable alternative to prevent fertility loss in cancer
      patients is the cryopreservation and transplantation of sexual tissues (ovaries
      and/or testes). There is a low rate of fertilization following cryopreservation
      of ovaries prior to implantation. Therefore, in our opinion, this low rate is
      caused by instable blood flow during organ transplantation. Thus, this study
      researches a canine ovarian model that focuses on direct exposure of ovaries with
      blood in an experimentally induced sinus-like cavity. We implanted this tissue on
      the muscular layer of the stomach, which is its most vascularized region.
      MATERIALS AND METHODS: Ovarian transplantation was conducted on T1 animals (n=5),
      bilateral ovariectomy was performed on T2 animals (n=5), unilateral ovariectomy
      was conducted on T3 cases and animals in the control-sham group (n=5) did not
      undergo ovariectomy or transplantation. RESULTS: All isotransplanted ovaries
      survived. Ovaries resumed follicular growth and revascularization. Transplanted
      ovaries contained 75%-76% of survived small follicles (pre antral) after 60 days.
      The ovarian granulosa cells showed considerable resistance against ischemia.
      After day 30 no statistically significant differences in the level of estradiol
      and progesterone were observed between T1 animals and the T3 group. T1 animals
      showed considerably high levels of progesterone and estradiol in comparison to T2
      cases. CONCLUSION: This study showed that using blood sinus method for ovarian
      isotransplantation helps ovarian tissue to survive from post implantation
      ischemia which confirms with normal follicles presentation and intact endocrine
      function of the implanted ovaries.

PMID- 24917922
TI  - Evaluation of nuchal translucency measurement in first trimester pregnancy.
AB  - BACKGROUND: A significant number of pregnancies, particularly in women with
      previous histories of infertility, are associated with fetal abnormalities.
      Methods such as the nuchal translucency (NT) measurement enable us to identify
      more pregnancies with chromosomal abnormalities. MATERIALS AND METHODS: This
      analytic cross-sectional study was performed in 446 pregnant women at 11-14 weeks
      gestation, from 2009 to 2010 in the Fetal Medicine Unit of Imam Khomeini
      Hospital, Ahvaz Jundishapur University of Medical Sciences. All NT measurements
      were performed by a certified sonographer using the Fetal Medicine Foundation
      (FMF) recommended protocol. FMF first trimester software was used for primary and
      secondary (adjusted) risk calculation. RESULTS: The average maternal age was 28.5
      years and 15% of mothers were >=35 years of age. The average crown rump length
      (CRL), gestational age and NT thickness were 61.7, 12.4 weeks and 1.75 mm,
      respectively. There were 20 cases with increased adjusted risk (4.04%) and 4
      cases of documented abnormal karyotype. CONCLUSION: In our study increased
      adjusted risk was 4.04%.Documented abnormal karyotype were 0.9% and 28% of total
      and high-risk groups who accepted amniocentesis, respectively. In this study, 50%
      of women with high-risk results and about half of those with abnormal karyotypes
      were seen in women under age 35. Knowing these risks is of utmost importance in
      pregnancy, particularly in patients with infertility histories.

PMID- 24917923
TI  - Long-term Developmental Effects of Lactational Exposure to Lead Acetate on Ovary
      in Offspring Wistar Rats.
AB  - BACKGROUND: During the last decades, environmental contamination by lead
      generated from human activities has become an evident concern. The present study
      assessed the long-term effects of neonatal exposure to different doses of lead
      acetate on the ovaries of offspring rats. MATERIALS AND METHODS: Pregnant female
      Wistar rats were randomly divided into a control and three experimental groups.
      The experimental groups received 20, 100 and 300 mg/L/day lead acetate via
      drinking water during lactation. Ovaries of the offspring were removed at 30, 60,
      90 and 120 days of age, their weights recorded and fixed in Bouin's solution.
      Following tissue processing, 5 MUm serial sections were stained with hematoxylin
      eosin, and then, the numbers and diameters of ovarian follicles and corpora lutea
      were estimated. RESULTS: Ovary weights decreased significantly (p<0.05) in the
      300 mg/L/day dose groups at 30, 60 and 90 days postnatal development. Significant
      dose-related decreases were seen in the numbers of primary, secondary and antral
      follicles in 100 (p<0.05) and 300 mg/L/day doses groups at 30 and 60 days of age
      (p<0.01). There was significant decrease in mean number of corpora lutea in the
      100 (p<0.05) and 300 (p<0.01) mg/L/day dose groups at 60 days of age. It seems
      that neonatal lead treatment has transient effects on follicular development in
      the ovary of offspring and ovarian parameters gradually improve until 90 days of
      age. CONCLUSION: The present study showed that maternal lead acetate exposure
      affects prepubertal ovarian follicle development in a dose dependent manner, but
      ovarian parameters gradually improve during the postpubertal period.

PMID- 24917924
TI  - Anti-coagulation during pregnancy in women with mechanical heart valves: a
      prospective study.
AB  - BACKGROUND: Pregnancy is associated with a hypercoagulable state, therefore the
      optimal anticoagulants for potential use in pregnant women with prosthetic heart
      valves are controversial. The aim of this study is to investigate the effect of
      anticoagulants on pregnancy outcomes and their potential risks in pregnant women
      with mechanical heart valves. MATERIALS AND METHODS: In this prospective cohort
      study, we followed 44 women with 49 pregnancies who had mechanical heart valves
      from September 2002 to September 2007. A total of 38 patients took warfarin
      throughout their pregnancies (group A). In 11 patients, warfarin was changed to
      heparin during the first trimester and then again to warfarin during 12thto
      36thweeks of gestational age (group B). All women took warfarin from 36thweeks of
      gestational age until delivery. RESULTS: In group A, there were 22 live births
      (57.9%), 15 abortions (39.5%) and 1 maternal death (2.6%). In group B, there were
      seven live births (63.6%), three spontaneous abortions (27.3%) and one intra
      uterine fetal death (9.1%). There was no significant difference in live birth
      rate between the two groups (p=0.24). Thirty-three pregnancies (86.8%) in group A
      and five pregnancies (45.4%) in group B had no maternal complications (p=0.004).
      The difference in pregnancy complications between both groups was significant
      (p<0.001). CONCLUSION: The present study shows that low dose warfarin (5 mg/day
      or less) may be safe during the first trimester of pregnancy. Maternal adverse
      events are low when pregnant women with mechanical heart valves remain on a
      warfarin regimen. The risk of embryopathy does not necessarily increase.

PMID- 24917925
TI  - Adipose-derived stem cells cooperate with fractional carbon dioxide laser in
      antagonizing photoaging: a potential role of Wnt and beta-catenin signaling.
AB  - BACKGROUND: It is well established that adipose-derived stem cells (ADSCs)
      produce and secrete cytokines/growth factors that antagonize UV-induced
      photoaging of skin. However, the exact molecular basis underlying the anti
      photoaging effects exerted by ADSCs is not well understood, and whether ADSCs
      cooperate with fractional carbon dioxide (CO2) laser to facilitate photoaging
      skin healing process has not been explored. Here, we investigated the impacts of
      ADSCs on photoaging in a photoaging animal model, its associated mechanisms, and
      its functional cooperation with fractional CO2 laser in treatment of photoaging
      skin. RESULTS: We showed that ADSCs improved dermal thickness and activated the
      proliferation of dermal fibroblast. We further demonstrated that the combined
      treatment of ADSCs and fractional CO2 laser, the latter which is often used to
      resurface skin and treat wrinkles, had more beneficial effects on the photoaging
      skin compared with each individual treatment. In our prepared HDF photoaging
      model, flow cytometry showed that, after adipose derived stem cells conditioned
      medium (ADSC-CM) co-cultured HDF photoaging model, the cell proliferation rate is
      higher than UVB irradiation induced HDF modeling (p < 0.05). Additionally, the
      expressions of beta-catenin and Wnt3a, which were up-regulated after the
      transplantation of ADSCs alone or in combination with fractional CO2 laser
      treatment. And the expression of wnt3a and beta-catenin has the positive
      correlation with photoaging related protein TGF-beta2 and COLI. We also verified
      these protein expressions in tissue level. In addition, after injected SFRP2 into
      ADSC-CM co-cultured HDF photoaging model, wnt3a inhibitor, compared with un
      intervened group, wnt3a, beta-catenin protein level significantly decreased.
      CONCLUSION: Both ADSCs and fractional CO2 laser improved photoaging skin at least
      partially via targeting dermal fibroblast activity which was increased in
      photoaging skin. The combinatorial use of ADSCs and fractional CO2 laser
      synergistically improved the healing process of photoaging skin. Thus, we provide
      a strong rationale for a combined use of ADSCs and fractional CO2 laser in
      treatment of photoaging skin in clinic in the future. Moreover, we provided
      evidence that the Wnt/beta-catenin signaling pathway may contribute to the
      activation of dermal fibroblast by the transplantation of ADSCs in both vitro and
      vivo experiment.

PMID- 24917926
TI  - Characterization of coagulase negative staphylococci from cases of subclinical
      mastitis in dairy cattle in Kampala, Uganda.
AB  - BACKGROUND: Coagulase negative staphylococci (CNS) are the most common pathogens
      leading to subclinical mastitis (SCM) in dairy cattle in Uganda. Coagulase
      negative staphylococci can vary between bacterial species in how they cause
      disease. The aim of the study was to characterize CNS, from cows with SCM in
      Uganda, at the species level. FINDINGS: Quarter milk samples (n = 166) were
      collected from 78 animals with SCM. Bacteriological analyses were carried out at
      Makerere University, Kampala, Uganda and at the National Veterinary Institute
      (SVA), Uppsala, Sweden. The most common pathogens found in milk samples from cows
      with SCM were CNS (31.7%). Two species of CNS were found, S. epidermidis (85%)
      and S. haemolyticus (15%). Of the CNS isolates, 16/20 (80%) were positive for
      beta-lactamase production (beta+). CONCLUSIONS: In milk samples from cows with
      SCM caused by CNS, S. epidermidis was most prevalent, followed by S.
      haemolyticus.

PMID- 24917927
TI  - Safety and efficacy of outpatient bronchoscopy in lung transplant recipients - a
      single centre analysis of 3,197 procedures.
AB  - BACKGROUND: Bronchoscopy represents an important diagnostic and therapeutic tool
      in the management of lung transplant (LTx) recipients. Outpatient bronchoscopy
      reduces health costs and may improve quality of life amongst these patients. This
      retrospective study assessed the safety and efficacy of outpatient bronchoscopy
      including trans-bronchial biopsy. METHODS: All outpatient bronchoscopies
      performed on lung transplant recipients between 1 August 2008 and 31 January 2011
      were reviewed. Sample quality, duration and complications were recorded. Cost
      analysis was performed from local trust financial data. RESULTS: A total of 3,197
      bronchoscopies were performed on 571 LTx recipients under topical anaesthesia.
      Fourteen percent of examinations required intravenous sedation. In 79.8% of
      examinations no complications were observed. Most complications were minor
      (17.9%) including cough (5.3%) and minimal bleeding after trans-bronchial biopsy
      (7.8%). Major complications (2.3%) were pneumothorax, severe bleeding and severe
      desaturation. No attributable deaths were recorded during the observation period.
      Quality of examination based on bronchoalveolar lavage recovery median (>50%) and
      biopsy results was adequate at 75% and 77.4%, respectively. Independent risk
      factors associated with complication were long-term oxygen therapy, sedation
      before examination, balloon dilatation and transbronchial biopsy. After excluding
      high-risk procedures annual savings per patient (2.2 bronchoscopies per year)
      were 2140?. CONCLUSIONS: Outpatient bronchoscopy after LTx is safe. The low
      complication rate could be attributed to withholding of intravenous sedation.
      Furthermore, it reduces health community costs.

PMID- 24917928
TI  - Changes in fetal mannose and other carbohydrates induced by a maternal insulin
      infusion in pregnant sheep.
AB  - BACKGROUND: The importance of non-glucose carbohydrates, especially mannose and
      inositol, for normal development is increasingly recognized. Whether pregnancies
      complicated by abnormal glucose transfer to the fetus also affect the regulation
      of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin
      infusions were used to reduce glucose supply to the fetus for both short (2-wk)
      and long (8-wk) durations to test the hypothesis that a maternal insulin infusion
      would suppress fetal mannose and inositol concentrations. We also used direct
      fetal insulin infusions (1-wk hyperinsulinemic-isoglycemic clamp) to determine
      the relative importance of fetal glucose and insulin for regulating non-glucose
      carbohydrates. RESULTS: A maternal insulin infusion resulted in lower maternal
      (50%, P < 0.01) and fetal (35-45%, P < 0.01) mannose concentrations, which were
      highly correlated (r(2) = 0.69, P < 0.01). A fetal insulin infusion resulted in a
      50% reduction of fetal mannose (P < 0.05). Neither maternal nor fetal plasma
      inositol changed with exogenous insulin infusions. Additionally, maternal insulin
      infusion resulted in lower fetal sorbitol and fructose (P < 0.01). CONCLUSIONS:
      Chronically decreased glucose supply to the fetus as well as fetal
      hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of
      these carbohydrates in protein glycosylation and lipid production, more research
      on their metabolism in pregnancies complicated by abnormal glucose metabolism is
      clearly warranted.

PMID- 24917929
TI  - Mitochondria and cancer.

PMID- 24917930
TI  - Integrating COPD care in Italy.

PMID- 24917931
TI  - Expression of aquaporins in bronchial tissue and lung parenchyma of patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Aquaporins AQP1 and AQP5 are highly expressed in the lung. Recent
      studies have shown that the expression of these proteins may be mechanistically
      involved in the airway inflammation and in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). The aim of this study was to investigate
      the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma
      of patients with COPD and COPD-resistant smokers. METHODS: Using a case-control
      design, we selected a group of 15 subjects with COPD and 15 resistant smokers
      (smokers without COPD) as a control, all of whom were undergoing lung resection
      surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the
      bronchial tissue and the lung parenchyma by means of immunohistochemistry and
      reverse-transcription real-time polymerase chain reaction. Tissue expression of
      AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and
      expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to
      3 (maximum). RESULTS: There were no significant differences in gene expression
      between COPD patients and resistant smokers both in the bronchial tissue and in
      the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the
      parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene
      showed the opposite pattern, with a 7.75-fold higher expression in the bronchus
      of smokers with COPD compared with controls. AQP1 and AQP5 proteins were
      preferentially expressed in endothelial cells, showing a higher intensity for
      AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an
      extension of 3 among patients with COPD). Subtle interstitial disease was
      associated with type II pneumocyte hyperplasia and an increased expression of
      AQP1. CONCLUSIONS: This study provides pilot observations on the differences in
      AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our
      findings suggest a potential role for AQP1 in the pathogenesis of COPD.

PMID- 24917932
TI  - Detection of piroplasms infection in sheep, dogs and hedgehogs in Central China.
AB  - BACKGROUND: Piroplasms are kinds of tick-borne parasitic apicomplexan protozoa,
      which are detrimental to humans and animals in tropical and subtropical areas
      around the world. Up until now, there has been a limited amount of reliable
      information available about the prevalence of piroplasms infections in wild
      animals in China. Therefore, we have investigated the infections of Babesia and
      Theileria species in both domestic and wild animals in Xinyang city, Henan
      province, where tick-borne diseases have recently been reported. This study aims
      to analyze the distribution patterns of piroplasms infections in animals, and
      assess their potential threat to humans in Central China. METHODS: Blood samples
      were collected from sheep, dogs and hedgehogs in two regions, including Shihe
      District and Luoshan County, of Xinyang city, Henan province from August to
      December 2012. Babesia spp. and Theileria spp. were detected by polymerase chain
      reaction (PCR) and identified by sequencing and phylogenetic analysis. Moreover,
      the characteristics of detected piroplasms in different animal hosts were
      compared between the two study regions. RESULTS: A total of 227 blood samples
      were collected from 73 sheep, two dogs and 152 hedgehogs. Babesia spp. was only
      detected in the two dogs. Theileria spp. was detected both in the sheep and the
      hedgehogs, and the total positive rate of Theileria spp. in the sheep and the
      hedgehogs was 57.53% and 13.82%, respectively. Sequencing and phylogenetic
      analysis revealed that the Theileria spp. detected in the sheep and the hedgehogs
      were very close to T. lunwenshuni cloned from a small ruminant and Theileria spp.
      isolated from a febrile hospitalized patient in China. CONCLUSION: Babesia and
      Theileria infections were detected in both domestic and wild animals in Xinyang
      city, Henan province in Central China, thus warranting further studies in these
      regions.

PMID- 24917933
TI  - Dysfunctional self-talk associated with eating disorder severity and
      symptomatology.
AB  - BACKGROUND: While self-talk has been argued to play a crucial role in the
      development and maintenance of eating disorders (EDs), it has received limited
      research attention. This study aimed to explore the relationship of ED self-talk
      with ED severity and symptomatology. METHODS: Analysis of the existing
      literature, supplemented with a small-scale pilot study, identified 24 distinct
      categories of ED self-talk. The main study involved the completion of on-line
      questionnaires by 172 women aged 18-49, recruited through clinical services, ED
      websites, and the general population. Participants were assigned to clinical (n =
      83) and non-clinical (n = 89) samples, using the Eating Disorder Examination
      Questionnaire to screen for ED psychopathology. RESULTS: Substantial differences
      in the levels of ED self-talk were found between the clinical and non-clinical
      populations. Principal components analysis, conducted within the clinical sample,
      revealed ED self-talk to have a two-component structure. Self-talk reflecting an
      'abusive relationship' between the sufferer and the ED strongly predicted overall
      severity and several aspects of symptomatology. 'Ascetic attitudes' towards
      thinness were linked with compulsive exercising and lower BMIs but not with
      overall severity. CONCLUSIONS: Close examination of the 'abusive relationship'
      component suggests a need to loosen the connection between negative appraisals of
      the abused self and the abusive voice of the ED so that the former can fulfil
      their potential as a force for change. Further, in seeking to counter the impact
      of the ED voice, it is suggested that the seducer and abuser roles require
      primary clinical focus.

PMID- 24917935
TI  - Introduction from the president.

PMID- 24917934
TI  - Pilot study employing heart rate variability biofeedback training to decrease
      anxiety in patients with eating disorders.
AB  - Heart rate variability (HRV) biofeedback, a technique which encourages slow
      meditative breathing, was offered to 25 in-patients with various eating disorder
      diagnoses-anorexia nervosa, bulimia nervosa and binge eating disorder. We found
      that this modality had no serious side effects, and was subjectively useful to
      most participants. An enhanced ability to generate highly coherent HRV patterns
      in patients with recent onset anorexia nervosa was observed. 

PMID- 24917936
TI  - Introductory message from the Editors.

PMID- 24917937
TI  - Linaclotide: A new drug for the treatment of chronic constipation and irritable
      bowel syndrome with constipation.
AB  - INTRODUCTION: Linaclotide is the first member of a novel class of drugs to be
      extensively evaluated for the treatment of chronic constipation (CC) and
      irritable bowel syndrome with constipation (IBS-C). AIM: To provide a
      comprehensive overview of the current state of knowledge on linaclotide, its
      pharmacological properties, mode of action and efficacy in clinical trials to
      date. METHODS: We conducted a systematic review of the literature. RESULTS: The
      survey revealed that linaclotide is a minimally absorbed, 14-amino acid peptide
      which acts in the intestinal lumen on guanylate cyclase-C (GC-C). This results in
      generation of cyclic guanosine monophosphate (cGMP), which stimulates chloride
      secretion, resulting in increased luminal fluid secretion and an acceleration of
      intestinal transit. In animal models, linaclotide also decreased visceral
      hypersensitivity. Linaclotide softened stool and increased transit in CC and in
      IBS-C. Phase II and phase III clinical studies established efficacy of
      linaclotide in CC (linaclotide 145 ug daily approved in the United States for CC)
      and in IBS-C (linaclotide 290 ug daily US Food and Drug Administration-approved
      for IBS-C, with favourable recommendation for the European Medicines Agency
      Committee for Medicinal Products for Human Use (CHMP). Linaclotide showed a
      favourable safety profile, and the main treatment-emerging adverse event was
      diarrhea, leading to discontinuation rates of up to 5%. Linaclotide is an
      important addition to the therapeutic possibilities for treating IBS-C and CC.

PMID- 24917938
TI  - Modern medical and surgical management of difficult-to-treat GORD.
AB  - Approximately 30-40% of patients taking proton pump inhibitors (PPIs) for
      presumed gastro-oesophageal reflux (GOR) symptoms do not achieve adequate symptom
      control, especially when no oesophageal mucosal breaks are present at endoscopy
      and when extra-oesophageal symptoms are concerned. After failure of optimization
      of medical therapy, a careful work up is mandatory that aims at determining
      whether symptoms are related to GOR or not. Most patients with refractory
      symptoms do not have GOR-related symptoms. Some may have symptoms related to
      weakly acidic reflux and/or oesophageal hypersensitivity. Baclofen is currently
      the only antireflux compound available as add-on therapy to PPIs, but its poor
      tolerability limits its use in clinical practice. There is room for pain
      modulators in patients with hypersensitive oesophagus and functional heartburn.
      Antireflux surgery is a suitable option in patients responding to medical therapy
      who want to avoid taking medication or if persisting symptoms can be clearly
      attributed to poorly controlled GOR. 

PMID- 24917939
TI  - Laparoscopy for extraperitoneal rectal cancer reduces short-term morbidity:
      Results of a systematic review and meta-analysis.
AB  - BACKGROUND: The role of laparoscopy in the treatment of extraperitoneal rectal
      cancer is still controversial. The aim of the study was to evaluate differences
      in safety of laparoscopic rectal resection for extraperitoneal cancer, compared
      with open surgery. MATERIALS AND METHODS: A systematic review from 2000 to July
      2012 was performed searching the MEDLINE and EMBASE databases (PROSPERO
      registration number CRD42012002406). We included randomized and prospective
      controlled clinical studies comparing laparoscopic and open resection for rectal
      cancer. Primary endpoints were 30-day mortality and morbidity. Then a meta
      analysis was conducted by a fixed-effect model, performing a sensitivity analysis
      by a random-effect model. Relative risk (RR) was used as an indicator of
      treatment effect. RESULTS: Eleven studies, representing 1684 patients, met the
      inclusion criteria: four were randomized for a total of 814 patients. Mortality
      was observed in 1.2% of patients in the laparoscopic group and in 2.3% of
      patients in the open group, with an RR of 0.56 (95% CI 0.19-1.64, p = 0.287). The
      overall incidence of short-term complications was lower in the laparoscopic group
      (31.5%) compared to the open group (38.2%), with an RR of 0.83 (95% CI 0.73-0.94,
      p = 0.004). Surgical complications, wound complications, blood loss and the need
      for blood transfusion, time for bowel movement recovery, food intake recovery,
      and hospital stay were significantly lower or less frequent in the laparoscopic
      group. The incidence of intra-operative injuries, anastomotic leakages, and
      surgical re-interventions was similar in the two groups. Only operative time was
      in favour of the open group. CONCLUSIONS: Based on the evidence of both
      randomized and prospective controlled series, mortality was lower after
      laparoscopy although not significantly so, while the short-term morbidity RR,
      including subgroup analysis, was significantly lower after laparoscopy for
      extraperitoneal rectal cancer compared to open surgery.

PMID- 24917940
TI  - Efficacy and safety of oral prucalopride in women with chronic constipation in
      whom laxatives have failed: an integrated analysis.
AB  - BACKGROUND: Prucalopride is a selective, high-affinity, 5-hydroxytryptamine
      (serotonin) type 4 (5-HT4) receptor agonist with gastrointestinal prokinetic
      activities. This integrated analysis of data from three double-blind phase III
      trials (ClinicalTrials.gov: NCT00488137, NCT00483886, NCT00485940) compared the
      efficacy and safety of prucalopride 2 mg once daily in women with chronic
      constipation [<=2 spontaneous complete bowel movements (SCBM) per week] in whom
      laxatives had failed to provide adequate relief with that in the all-patient (AP)
      population of men and women with chronic constipation who had or had not obtained
      relief from laxatives. METHODS: Patients received prucalopride 2 mg or placebo
      once-daily for 12 weeks. Efficacy endpoints included an average of >=3 SCBM/week
      and average increases of >=1 SCBM/week and >=1 SBM/week over this period. A
      response on any of these three endpoints was considered to be clinically
      relevant, and an overall response rate was derived for patients satisfying any of
      these endpoints. RESULTS: Of the AP population (n = 1318), 936 were women in whom
      laxatives had failed to provide adequate relief (WLF). More patients on
      prucalopride 2 mg than placebo had an average of >=3 SCBM/week (AP 24.4 vs 11.0%;
      WLF 24.7 vs 9.2%), an average increase of >=1 SCBM/week (AP 43.5 vs 24.8%; WLF
      44.2 vs 22.6%), and an average increase of >=1 SBM/week (AP 66.7 vs 38.4%; WLF
      68.3 vs 37.0%) (all p < 0.001). Significant differences from placebo were evident
      in week 1 and sustained thereafter. Overall response rates in the AP and WLF
      populations, respectively, were 69.7 and 71.0% with prucalopride 2 mg and 44.5
      and 41.6% with placebo (p < 0.001). Early (weeks 1-4) response predicted ultimate
      response over time. Common (>10%) adverse events were abdominal pain, nausea,
      diarrhoea, and headache. CONCLUSIONS: Prucalopride 2 mg once daily is effective
      in WLF. The efficacy and safety profile observed in WLF was similar to that in
      the total evaluated population of patients with chronic constipation who had or
      had not obtained adequate relief from laxatives.

PMID- 24917941
TI  - Etiology, endoscopic management and mortality of upper gastrointestinal bleeding
      in patients with cancer.
AB  - BACKGROUND: The source and outcomes of upper gastrointestinal bleeding (UGIB) in
      oncologic patients are poorly investigated. OBJECTIVE: The study aimed to
      investigate these issues in a tertiary academic referral center specialized in
      cancer treatment. METHODS: This was a retrospective study including all patients
      with cancer referred to endoscopy due to UGIB in 2010. RESULTS: UGIB was
      confirmed in 147 (of 324 patients) referred to endoscopy for a suspected episode
      of GI bleeding. Tumor was the most common cause of bleeding (N = 35, 23.8%),
      followed by varices (N = 30, 19.7%), peptic ulcer (N = 29, 16.3%) and
      gastroduodenal erosions (N = 16, 10.9%). Among the 32 patients with cancer of the
      upper GI tract, the main causes of bleeding were cancer (N = 27, 84.4%) and
      peptic ulcer (N = 5, 6.3%). Forty-one patients (27.9%) presented with bleeding
      from the primary tumor or from a metastatic lesion, and seven received endoscopic
      therapy, with successful initial hemostasis in six (85.7%). Rebleeding and
      mortality rates were not different between endoscopically treated (N = 7) and non
      treated (N = 34) patients (28.6% vs. 14.7%, p = 0.342; 43.9% vs. 44.1%, p =
      0.677). Median survival was 20 days, and the overall 30-day mortality rate was
      44.9%. There was no predictive factor of mortality or rebleeding. CONCLUSION:
      Tumor bleeding is the most common cause of UGIB in cancer patients. UGIB in
      cancer patients correlates with a high mortality rate regardless of the bleeding
      source. Current endoscopic treatments may not be effective in preventing
      rebleeding or improving survival.

PMID- 24917942
TI  - UEG Week 2012 award winners.

PMID- 24917943
TI  - UEG Support Policies: LINK Award Programme 2012.

PMID- 24917944
TI  - Synopsis of recent guidelines on pancreatic exocrine insufficiency.
AB  - BACKGROUND: In recent years, three national gastroenterology societies
      established guidelines for the diagnosis and therapy of pancreatic exocrine
      insufficiency (PEI). In addition, the Cochrane Collaboration issued a review.
      OBJECTIVE: The purpose of this paper is to present an overview of the
      recommendations and concordance between the four recent published guidelines and
      stimulate further discussion. METHODS: A review of the Australian, German and
      Italian guidelines and the Cochrane review was conducted, and a synthesis was
      made of common statements. RESULTS: There is a high degree of agreement on almost
      all items within these guidelines, both in the diagnosis of PEI and in terms of
      therapy and approach to management of PEI. In addition, novel emerging
      developments are highlighted, such as the fecal elastase-1 test, which is widely
      used but is not suitable for measuring mild-to-moderate PEI despite its ability
      to positively establish the diagnosis of severe PEI. One of the few novel tests
      proving to be useful is the (13)C mixed-chain triglycerides (MCT) breath test.
      This test, albeit an excellent quantitative test, is not widely used and is
      rarely available. The use of this test is making it apparent that there is a
      difference between treating the symptoms of PEI and treating malnutrition, the
      broader underlying defect. This may have direct consequences for the dosing of
      pancreatic enzymes (pancreatin), in that the consensus starting dose of all
      guidelines may be too low for some patients. Although chronic pancreatitis in
      adults and cystic fibrosis in children account for the main evidence base used
      for PEI, other indications are also discussed. CONCLUSIONS: There is good
      concordance between recommendations provided by international groups. More
      prospective studies are required in many areas, including the use of pancreatic
      enzymes in other gastrointestinal disorders, such as celiac disease and irritable
      bowel syndrome (IBS). We also need to assess the feasibility of the (13)C MCT
      breath test. At the same time, it needs to be confirmed that higher doses of
      pancreatic enzymes are really necessary to not only relieve the symptoms of PEI
      but also treat malnutrition appropriately.

PMID- 24917945
TI  - Molecular imaging in endoscopy.
AB  - Molecular imaging focuses on the molecular signature of cells rather than
      morphological changes in the tissue. The need for this novel type of imaging
      arises from the often difficult detection and characterization especially of
      small and/or premalignant lesions. Molecular imaging specifically visualizes
      biological properties of a lesion and might thereby be able to close diagnostic
      gaps, e.g. when differentiating hyperplastic from neoplastic polyps or detecting
      the margins of intraepithelial neoplastic spread. Additionally, not only the
      detection and discrimination of lesions could be improved: based on the molecular
      features identified using molecular imaging, therapy regimens could be adjusted
      on the day of diagnosis to allow for personalized medicine and optimized care for
      each individual patient. 

PMID- 24917947
TI  - Comparison of transhepatic and extrahepatic routes for EUS-guided rendezvous
      procedure for distal CBD obstruction.
AB  - BACKGROUND: EUS-guided rendezvous procedure (EUS-RV) can be done by the
      transhepatic (TH) or the extrahepatic (EH) route. There is no data on the
      preferred access route when both routes are available. STUDY AIM: To compare the
      success, complications, and duration of hospitalization for patients undergoing
      EUS-RV by the TH or the EH route. PATIENTS AND METHODS: Patients with distal
      common bile duct (CBD) obstruction, who failed selective cannulation, underwent
      EUS-RV by the TH route through the stomach or the EH route through the duodenum.
      RESULTS: A total of 35 patients were analysed (17 TH, 18 EH). The mean procedure
      time was significantly longer for the TH group (34.4 vs. 25.7 min; p = 0.0004).
      There was no difference in the technical success (94.1 vs. 100%). However, the TH
      group had a higher incidence of post-procedure pain (44.1 vs. 5.5%; p = 0.017),
      bile leak (11.7 vs. 0; p = 0.228), and air under diaphragm (11.7 vs. 0; p =
      0.228). All bile leaks were small and managed conservatively. Duration of
      hospitalization was significantly higher for the TH group (2.52 vs. 0.17 days; p
      = 0.015). CONCLUSIONS: EUS-RV has similar success rate by the TH or the EH route.
      However, the TH route has higher post-procedure pain, longer procedure time, and
      longer duration of hospitalization. The EH route should be preferred for EUS-RV
      in patients with distal CBD obstruction when both access routes are technically
      feasible.

PMID- 24917946
TI  - Comparison of a standard fully covered stent with a super-thick silicone-covered
      stent for the treatment of refractory esophageal benign strictures: A prospective
      multicenter study.
AB  - BACKGROUND: Some esophageal strictures resist endoscopic treatments. There is a
      need for new treatments, such as specifically designed stents. OBJECTIVE: Our
      study sought to compare the results achieved with a standard, fully covered
      metallic stent (FCMS) and those achieved using a stent designed specifically for
      benign strictures (BS-FCMS). PATIENTS AND METHODS: The study used a prospective,
      multicenter, controlled design, with patients recruited from tertiary referral
      centers. Patients with refractory esophageal strictures were included. Standard
      FCMS were used in group 1 (N = 24), and BS-FCMS were used in group 2 (N = 17).
      Patients were followed for 24 months after stent removal. The main outcomes
      measured were stricture resolution rate, 24 months' recurrence rate and stent
      related morbidity. RESULTS: Early stent migrations occurred in one (4.1%) patient
      from group 1 and five (29.4%) from group 2 (p < 0.05). During esophageal
      stenting, complications occurred in six patients (25%) in group 1 and six
      patients (35.3%) in group 2 (p = 0.47), respectively. Fifty percent of
      complications were attributed to migration. There was no procedure-related
      morbidity associated with the extraction of the stent. The stricture resolution
      rate was, respectively, 95.2% in group 1 and 87.5% in group 2 (the difference
      between the two groups is not significant). During follow-up, stricture
      recurrence occurred in 15/19 patients (group 1, 79%) and 7/8 patients (group 2,
      87.5%; p = 1.0). The median time to recurrence of esophageal stricture was 1.7
      months (group 1, 0.6-12 months) and 1 month (group 2, 0.1-6 months). Study
      limitations include its nonrandomized design. CONCLUSION: The stricture
      resolution rate was high at the end of the stenting period for both types of
      stents without any statistical difference between the two groups, but the long
      term results were disappointing, with stricture recurring frequently and rapidly
      in both groups.

PMID- 24917948
TI  - Smoking, breastfeeding, physical inactivity, contact with animals, and size of
      the family influence the risk of inflammatory bowel disease: A Slovak case
      control study.
AB  - BACKGROUND: The aetiology of inflammatory bowel disease (IBD) is not known but is
      likely to involve a combination of genetic predisposition and environmental risk
      factors. Smoking has been associated consistently with a higher risk of Crohn's
      disease (CD), while appendectomy and smoking appear to diminish the risk of
      ulcerative colitis (UC). The roles of other environmental factors are unclear.
      The aim of the present study was to evaluate the association of CD and UC with
      several environmental risk factors. METHODS: This case-control study included 338
      patients (190 CD, 148 UC) and 355 controls. All subjects completed a detailed
      questionnaire regarding breastfeeding duration, history of helminthic infections,
      allergic diseases, appendectomy, household size, housing type, contact with
      specific domestic animals, physical activity, and smoking. Associations between
      risk factors and CD and UC were investigated by univariate and multivariate
      analysis. RESULTS: On multivariate analysis, CD associated with smoking at
      diagnosis (odds ratio, OR, 3.7, 95% CI 2.2-6.2; p < 0.001), being breastfed for
      <6 months (OR 2.7, 95% CI 1.7-4.4; p < 0.001), and less than two childhood
      sporting activities weekly (OR 2.7, 95% CI 1.5-5.0; p < 0.001) and inversely
      associated with frequent contact with cats in childhood (OR 0.6, 95% CI 0.4-0.9;
      p < 0.03). UC associated with less than two sporting weekly activities in
      childhood (OR 2.0, 95% CI 1.1-3.5, p = 0.02), fewer household members in
      childhood (OR 0.8, 95% CI 0.7-0.98, p = 0.03), and being breastfed for <6 months
      (OR 1.7, 95% CI 1.02-2.8, p = 0.04). A composite environmental risk index for CD
      revealed that 47 and 14% of the controls and patients with CD had no risk
      factors, respectively, and that 14 and 38% of the controls and patients with CD
      had at least two risk factors, respectively. CONCLUSION: CD and UC associated
      with infrequent childhood sports activities and short breastfeeding. Furthermore,
      CD associated with smoking and infrequent contact with animals in childhood. UC
      associated with a smaller family size in childhood.

PMID- 24917950
TI  - UEG Week attendance and abstract submission: What's in it for me?

PMID- 24917951
TI  - Jean-Paul Galmiche, winner of the UEG Lifetime Achievement Award 2012.

PMID- 24917949
TI  - Endomicroscopy in bile duct: Inflammation interferes with pCLE applied in the
      bile duct: A prospective study of 54 patients.
AB  - BACKGROUND: The preoperative diagnosis of biliary stenosis is associated with low
      accuracy. As a consequence, probe-based confocal laser endomicroscopy (pCLE), an
      in-vivo histological imaging technique, was applied in the bile duct. The aim of
      this study was to establish whether previous inflammation of the bile duct
      affects confocal interpretation. The findings from pCLE were compared in two
      groups of patients: those in whom there had been no cholangitis nor stenting and
      those in whom stents had been used and subsequently retrieved or who had suffered
      cholangitis. PATIENTS AND METHODS: pCLE was performed on 54 patients (mean age 66
      years; 31 men, 23 women) from September 2008 to July 2011. Patients were divided
      in two groups: group 1: 39 patients who had not undergone a biliary procedure in
      the month preceding the pCLE procedure; and group 2: 15 patients who had
      undergone stent placement or presented with cholangitis in the month preceding
      the pCLE procedure. Endoscopic and pCLE data were collected prospectively. pCLE
      results were compared to benchmark histology (surgery, endoultrasonography,
      percutaneous biopsy). Patients with a benign stricture who did not undergo
      operation were followed for 1 year. pCLE images of the bile duct were obtained
      during endoscopic retrograde cholangiopancreatography procedures. pCLE images
      were interpreted prospectively using the Miami classification in vivo and in real
      time. RESULTS: In group 1, sensitivity, specificity, and accuracy were 88, 83,
      and 87%, respectively. In group 2, sensitivity, specificity, and accuracy were
      75, 71, and 73%, respectively. Diagnostic accuracy of pCLE was lower when applied
      to group 2 (p < 0,001). The investigation is less reliable in bile ducts affected
      by inflammation from cholangitis or previous stenting. CONCLUSIONS: Inflammatory
      lesions of the bile duct interfere with interpretation of pCLE. A refined pCLE
      description of inflammatory lesions should improve accuracy of pCLE in bile duct
      stenosis.

PMID- 24917954
TI  - Endoscopic colorectal cancer screening provides long-lasting effect.

PMID- 24917952
TI  - Treatment of GORD: Three decades of progress and disappointments.
AB  - The treatment of GORD has been revolutionized by the introduction, in the 1980s,
      of proton-pump inhibitors as the mainstay of medical therapy and by the
      development of laparoscopic antireflux surgery which has definitively replaced
      open surgery. However, despite these major advances, many unmet therapeutic needs
      still persist and justify novel therapeutic approaches. The aim of this
      historical review is to recall the main discoveries in the treatment of GORD that
      have occurred during the last three decades and to discuss why some initially
      promising drugs or techniques have not translated into clinical applications. A
      careful analysis of these previous disappointing experiences should help to
      identify high priorities and better research programmes on the management of
      GORD. 

PMID- 24917953
TI  - Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment.
AB  - Lactose malabsorption is a common condition caused by reduced expression or
      activity of lactase in the small intestine. In such patients, lactose intolerance
      is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after
      ingestion of dairy products. The genetic basis of lactose malabsorption is
      established and several tests for this condition are available, including
      genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is
      less well understood. Recent studies show that the risk of symptoms after lactose
      ingestion depends on the dose of lactose, lactase expression, intestinal flora,
      and sensitivity of the gastrointestinal tract. Lactose intolerance has recently
      been defined as symptoms developing after ingestion of lactose which do not
      develop after placebo challenge in a person with lactose maldigestion. Such
      blinded testing might be especially important in those with functional
      gastrointestinal diseases in whom self-reported lactose intolerance is common.
      However, placebo-controlled testing is not part of current clinical practice.
      Updated protocols and high-quality outcome studies are needed. Treatment options
      of lactose intolerance include lactose-reduced diet and enzyme replacement.
      Documenting the response to multiple doses can guide rational dietary management;
      however, the clinical utility of this strategy has not been tested. This review
      summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption
      and intolerance. 

PMID- 24917955
TI  - Long-term effectiveness of endoscopic screening on incidence and mortality of
      colorectal cancer: A randomized trial.
AB  - BACKGROUND: Due to few randomized trials, there is uncertainty about the long
      time effect of endoscopic screening on colorectal cancer (CRC) incidence and
      mortality. AIM: To evaluate the long-term effect of endoscopic screening on CRC
      incidence and mortality, we performed a population-based randomized controlled
      trial in Norway. MATERIALS AND METHODS: In 1983, 799 Norwegian men and women, age
      50-59 years were drawn from the population registry and randomly assigned to
      flexible sigmoidoscopy screening (400 individuals), or no screening (399
      individuals). Colonoscopy surveillance was offered after two and six years for
      all polyp-bearers in the screening group. In 1996, both groups were offered
      colonoscopy. Only individuals with advanced adenomas at colonoscopy in 1996 were
      recommended surveillance. All individuals were followed through Norwegian
      registries until 2008. Hazard ratios (HR) for CRC incidence, and CRC and overall
      mortality rates were calculated. RESULTS: During 26 years of follow up (17,327
      person-years), 26 colorectal cancers were observed: seven in the screening group
      and 19 in the control group (HR in screening group 0.40, 95% CI 0.17-0.95, p =
      0.04). Eight individuals died of colorectal cancer; one in the screening group
      and seven in the control group (HR 0.16, 95% CI 0.02-1.28, p = 0.08).
      CONCLUSIONS: This first randomized trial on the long-term effect of endoscopic
      screening shows reduced CRC incidence and mortality if screening is combined with
      rigorous surveillance for individuals with polyps. Colonoscopy screening without
      such surveillance may not be effective.

PMID- 24917956
TI  - Hiatal hernia predisposes to nocturnal gastro-oesophageal reflux.
AB  - BACKGROUND: Nocturnal reflux has been associated with severe complications of
      gastro-oesophageal reflux disease and a poorer quality of life. Hiatal hernia
      predisposes to increased oesophageal acid exposure, but the effect on night
      reflux symptoms has never been investigated. The aim of the study was to
      investigate if hiatal hernia is associated with more frequent and severe night
      reflux symptoms. METHODS: A total of 215 consecutive patients (110 male, mean age
      52.6 +/- 14.7 years) answered a detailed questionnaire on frequency and severity
      of specific day and night reflux symptoms. Subsequently, all patients underwent
      upper endoscopy and were categorized in two groups based on the endoscopic
      presence of hiatal hernia. RESULTS: Patients with hiatal hernia were more likely
      to have nocturnal symptoms compared to those without hiatal hernia (78.6 vs.
      51.8%, p = 0.0001); 59.2% of patients with hiatal hernia reported heartburn and
      60.2% regurgitation compared to 43.8 and 39.3% of those without hiatal hernia,
      respectively (p = 0.033 and p = 0.003). The proportions of patients with day
      heartburn or regurgitation were not significantly different between the two
      groups. Night heartburn and regurgitation were graded as significantly more
      severe by patients with hiatal hernia (4.9 +/- 4.2 vs. 3.2 +/- 3.7, p = 0.002,
      and 3.8 +/- 4.2 vs. 2.2 +/- 3.5, p = 0.001, respectively). Patients with hiatal
      hernia had more frequent weekly night heartburn and regurgitation compared to
      those without hiatal hernia (p = 0.004 and p = 0.008, respectively). CONCLUSIONS:
      More patients with hiatal hernia reported nocturnal reflux symptoms compared to
      those without hiatal hernia. Furthermore, nocturnal reflux symptoms were
      significantly more frequent and graded as significantly more severe in patients
      with presence of hiatal hernia rather than in those without hiatal hernia.

PMID- 24917957
TI  - Validation of the GerdQ questionnaire for the management of gastro-oesophageal
      reflux disease in Japan.
AB  - BACKGROUND: The GerdQ scoring system may be a useful tool for managing gastro
      oesophageal reflux disease. However, GerdQ has not been fully validated in Asian
      countries. OBJECTIVE: To validate the Japanese version of GerdQ and to compare
      this version to the Carlsson-Dent questionnaire (CDQ) in both general and
      hospital-based populations. METHODS: The questionnaires, including the Japanese
      versions of GerdQ and CDQ, and questions designed to collect demographic
      information, were sent to a general population via the web, and to a hospital
      based population via conventional mail. The optimal cutoff GerdQ score and the
      differences in the characteristics between GerdQ and CDQ were assessed. RESULTS:
      The answers from 863 web-responders and 303 conventional-mail responders were
      analysed. When a GerdQ cutoff score was set at 8, GerdQ significantly predicted
      the presence of reflux oesophagitis. Although the GerdQ scores were correlated
      with the CDQ scores, the concordance rates were poor. Multivariate analysis
      results indicated that, the additional use of over-the-counter medications was
      associated with GerdQ score >= 8, but not with CDQ score >= 6. CONCLUSIONS: The
      GerdQ cutoff score of 8 was appropriate for the Japanese population. Compared
      with CDQ, GerdQ was more useful for evaluating treatment efficacy and detecting
      patients' unmet medical needs.

PMID- 24917958
TI  - Gastric obstruction after endoscopic submucosal dissection.
AB  - BACKGROUND: Bleeding and perforation are two major complications of gastric
      endoscopic submucosal dissection (ESD). There are only a few reports concerning
      gastric obstruction related to ESD in the stomach. OBJECTIVE: The aim of this
      study was to clarify the clinicopathological features of patients who experienced
      gastric obstruction after gastric ESD. METHODS: Clinicopathological data of 1878
      patients who underwent gastric ESD from September 2002 to December 2010 were
      retrospectively reviewed. Data of lesion location, circumference, circumferential
      extent of ESD ulcer, specimen diameter, depth of cancer, ulcer findings within
      the lesion, curability of ESD, number of simultaneous lesions, and occurrence of
      post-operative bleeding and perforation were collected. The risk of gastric
      obstruction regarding lesion and procedure related factors were assessed, and
      treatment for these patients was studied. RESULTS: Gastric obstruction was
      observed in 2.5% of the patients (47/1878). Symptoms occurred in a median of 24
      days after ESD. The incidence among patients with lesions in the upper part of
      the stomach was 4.7% (17/316), 0.36% (3/818) in the middle, and 3.8% (27/699) in
      the lower part. In relation to the circumferential extent, the incidence was 50%
      (33/66) among patients with a resection of >75% of the circumference. Stenosis
      was observed in 87% (41/47) of patients with gastric obstruction. Endoscopic
      balloon dilation was performed in 45 patients. Perforation due to EBD occurred in
      four patients; one was referred to surgery. CONCLUSIONS: Patients with a wide
      resection of >75% of the circumference should be considered for early repeat
      endoscopy after ESD, and dilation should be performed with caution if found to
      have stenosis.

PMID- 24917959
TI  - A cross sectional study of colonic diverticulosis in the London Bangladeshi
      population.
AB  - BACKGROUND: Diverticular disease is the most common morphological abnormality of
      the colon and the fifth most important gastrointestinal disease in terms of cost
      in the Western world. Tower Hamlets is the poorest borough in London containing a
      large Bangladeshi community. We observed that emergency admissions with
      complications of colonic diverticulosis were minimal in the Bangladeshi
      community. The objective was to compare the background prevalence of colonic
      diverticulosis in Bangladeshis with other ethnicities in patients undergoing
      colonoscopy at a single centre in Tower Hamlets. METHODS: Four thousand four
      hundred and fifty-four consecutive colonoscopy reports over a 2-year period were
      retrospectively analysed. Patients under 40 years of age and repeat colonoscopies
      were excluded, leaving 3151 patients (mean age: 63 years; 48% male). Demographics
      including ethnicity and medical background were retrieved from the electronic
      patient record system and findings correlated with the prevalence of other
      'Western' diseases in the cohort. RESULTS: Six hundred and thirty out of 3151
      (20%) colonoscopies were performed on Bangladeshis. The prevalence of colonic
      diverticulosis was significantly lower in Bangladeshis (17/630: 2.7%) than
      Caucasians (673/1869: 36%), Indians/Pakistanis (16/161: 9.9%), Oriental (15/44:
      34%) and Black (90/369: 24.4%) patient groups (chi(2) p < 0.0001 for all
      comparisons). The prevalence of classical sigmoid diverticulosis in the
      Bangladeshi cohort was only 1.0%, despite significantly more Bangladeshi patients
      undergoing colonoscopy for abdominal pain (p < 0.0001, chi(2)) and diarrhoea (p <
      0.0034, chi(2)). There was also a significantly greater incidence of type 2
      diabetes mellitus and ischaemic heart disease (p < 0.0001, chi(2)) in Bangladeshi
      patients. CONCLUSIONS: There is a negligible prevalence of colonic diverticulosis
      in the Bangladeshi population of London who undergo colonoscopy. This is in spite
      of a high incidence of type 2 diabetes and ischaemic heart disease. The effect of
      diet and genetics on the prevalence of colonic diverticulosis in Bangladeshis is
      not known and merits further investigation.

PMID- 24917960
TI  - Clinical outcomes using a faecal immunochemical test for haemoglobin as a first
      line test in a national programme constrained by colonoscopy capacity.
AB  - INTRODUCTION: Because of their many advantages, faecal immunochemical tests (FIT)
      are superseding traditional guaiac-based faecal occult blood tests in bowel
      screening programmes. METHODS: A quantitative FIT was adopted for use in two
      evaluation National Health Service (NHS) Boards in Scotland using a cut-off
      faecal haemoglobin concentration chosen to give a positivity rate equivalent to
      that achieved in the Scottish Bowel Screening Programme. Uptake and clinical
      outcomes were compared with results obtained contemporaneously in two other
      similar NHS Boards and before and after the evaluation in the two evaluation NHS
      Boards. RESULTS: During the evaluation, uptake was 58.5%. This was higher than in
      the same NHS Boards both before and after the evaluation, higher than in the
      other two NHS Boards and higher than the 53.7% achieved overall in Scotland. The
      overall positivity rate was higher in men than in women and increased with age in
      both genders. Positive predictive values for cancer (4.8%), high-risk adenoma
      (23.3%), all adenoma (38.2%) and all neoplasia (43.0%) in the two test NHS Boards
      were similar in all groups. CONCLUSIONS: In summary, this evaluation of the FIT
      supports the introduction of FIT as a first-line test, even when colonoscopy
      capacity is limited.

PMID- 24917962
TI  - UEG Education: What's that all about?

PMID- 24917961
TI  - Fistulizing Crohn's disease: Diagnosis and management.
AB  - Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for
      multidisciplinary management. Perianal fistulas are the most frequent findings in
      fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are
      associated with considerable morbidity and mortality. Detailed evaluation of the
      fistula tract by advanced imaging techniques is required to determine the most
      suitable management options. The fundamentals of perianal fistula management are
      to evaluate the complexity of the fistula tract, and exclude proctitis and
      associated abscess. The main goals of the treatment are abscess drainage, which
      is mandatory, before initiating immunosuppressive medical therapy, resolution of
      fistula discharge, preservation of continence and, in the long term, avoidance of
      proctectomy with permanent stoma. The management of enterocutaneous fistulas
      comprises of sepsis control, skin care, nutritional optimization and, if needed,
      delayed surgery. 

PMID- 24917963
TI  - UEG Week: Late-breaking abstract submission.

PMID- 24917964
TI  - UEG Rising Stars Award.

PMID- 24917965
TI  - Do we need to eradicate Helicobacter pylori in patients with GORD?
AB  - Eradication of Helicobacter pylori should not be avoided because of complicated
      reflux symptoms. Previously, although H. pylori eradication in patients with GORD
      was considered to induce unfavourable effects that worsen reflux symptoms, recent
      reports indicates that it can have favourable consequences by reducing symptoms
      and therefore improving quality of life, especially in GORD patients without
      severe corpus atrophy or severe hiatal herniation. 

PMID- 24917966
TI  - The effect of Helicobacter pylori infection and eradication in patients with
      gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo
      controlled multicentre study.
AB  - OBJECTIVES: This study aimed to resolve controversy regarding the effects of
      Helicobacter pylori eradication therapy and H. pylori infection in gastro
      oesophageal reflux disease. DESIGN: A randomized, double-blind, multicentre trial
      was performed in patients presenting with reflux symptoms. H. pylori-positive
      patients were randomized to receive either antibiotics or placebo for 7 days. H.
      pylori-negative patient controls received placebo. All received esomeprazole 20
      mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were
      followed up for 32 weeks by telephone. RESULTS: In this study, 198/589 (34%)
      patients were H. pylori-positive and 113 H. pylori-negative patients served as
      controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los
      Angeles grade BCD oesophagitis with no difference between patient groups. Symptom
      improvement on esomeprazole was seen in 89%. H. pylori eradication was successful
      in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio
      1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower
      probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6,
      95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis
      grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). CONCLUSION: Relapse of
      gastro-oesophageal reflux disease symptoms after a course of high dose acid
      suppression took longer for H. pylori-positive patients than H. pylori-negative
      controls; however eradication therapy had no effect on the risk of relapse;
      ClincialTrials.gov number, NCT00574925.

PMID- 24917967
TI  - Diagnosing early Barrett's neoplasia and oesophageal squamous cell neoplasia by
      bioimpedance spectroscopy in human tissue.
AB  - BACKGROUND: Detection of early oesophageal cancer in surrounding normal tissue
      can be challenging, but detection is essential to determine the subsequent
      treatment. Dysplastic tissue can be detected by using electrical impedance
      spectroscopy (EIS). OBJECTIVE: The aim of the present study was to evaluate the
      feasibility and value of EIS in the diagnosis of oesophageal neoplasia. METHODS:
      This prospective ex-vivo study included 23 patients with early oesophageal cancer
      (17 with Barrett's cancer and six with early squamous cell cancer). Immediately
      after endoscopic resection, the electrical properties of the resected specimens
      were investigated using a pencil probe (5 mm in diameter, frequency range from
      100 Hz to 1 MHz). Punch biopsies were taken from the measured site in order to
      compare the results of EIS with histology. RESULTS: EIS was able to detect
      dysplastic oesophageal mucosa with a high rate of accuracy (82% in Barrett's
      oesophagus and 100% in squamous oesophagus) A total of 54 different sites in 26
      tumours were evaluated. CONCLUSIONS: EIS was able to differentiate reliably
      between non-neoplastic and neoplastic oesophageal mucosa. Using EIS, it might be
      possible to use it for targeted biopsies and to avoid unnecessary biopsies during
      cancer surveillance in future.

PMID- 24917968
TI  - Oesophageal baseline impedance values are decreased in patients with eosinophilic
      oesophagitis.
AB  - BACKGROUND: Gastro-oesophageal reflux has been suggested to play a role in
      eosinophilic oesophagitis (EoO). Oesophageal acid exposure decreases baseline
      intraluminal impedance, a marker of mucosal integrity, in patients with gastro
      oesophageal reflux disease (GORD). OBJECTIVES: The aim of this study was to
      assess oesophageal baseline impedance levels in EoO patients and to investigate
      their relationship with oesophageal acid exposure. METHODS: Ambulatory 24-h pH
      impedance monitoring was performed in 11 EoO patients and in 11 healthy controls
      with matched oesophageal acid exposure. We assessed baseline impedance levels in
      the distal, mid-, and proximal oesophageal impedance channels. RESULTS: BASELINE
      IMPEDANCE LEVELS IN EOO PATIENTS WERE MARKEDLY LOWER COMPARED TO CONTROLS IN THE
      DISTAL OESOPHAGUS (MEDIAN (INTERQUARTILE RANGE): 988 (757-1978) vs. 2259 (1767
      2896) Omega, p = 0.015), mid-oesophagus (1420 (836-2164) vs. 2614 (2374-3879)
      Omega, p = 0.003), and proximal oesophagus (1856 (1006-2625) vs. 2868 (2397-3439)
      Omega, p = 0.005). Whereas baseline impedance decreased from proximal to distal
      in healthy subjects (p = 0.037), no such gradient was seen in EoO patients (p =
      0.123). CONCLUSIONS: Throughout the oesophagus, baseline impedance values are
      decreased in EoO patients, indicating impaired mucosal integrity. Our findings
      suggest that factors other than acid reflux are the cause of low baseline
      impedance in EoO.

PMID- 24917969
TI  - Oesophageal pressure-flow metrics in relation to bolus volume, bolus consistency,
      and bolus perception.
AB  - BACKGROUND: The utility of combined oesophageal pressure-impedance recording has
      been enhanced by automation of data analysis. OBJECTIVE: To understand how
      oesophageal function as measured by automated impedance manometry (AIM) pressure
      flow analysis varies with bolus characteristics and subjective perception of
      bolus passage. METHODS: Oesophageal pressure-impedance recordings of 5 and 10 ml
      liquid or viscous swallows and 2 and 4 cm solid swallows from 20 healthy control
      subjects (five male; 25-73 years) were analysed. Metrics indicative of bolus
      pressurization (intrabolus pressure and intrabolus pressure slope) were derived.
      Bolus flow resistance, the relationship between bolus pressurization and flow
      timing, was assessed using a pressure-flow index. Bolus retention was assessed
      using the ratio of nadir impedance to peak pressure impedance (impedance ratio).
      Subjective perception of bolus passage was assessed swallow by swallow. RESULTS:
      Viscosity increased the bolus flow resistance and reduced bolus clearance.
      Responses to boluses of larger volume and more viscous consistency revealed a
      positive correlation between bolus pressurization and oesophageal peak pressure.
      Flow resistance was higher in subjects who perceived bolus hold up of solids.
      CONCLUSIONS: Bolus volume and bolus type alter oesophageal function and impact
      AIM analysis metrics descriptive of oesophageal function. Perception of bolus
      transit was associated with heightened bolus pressurization relative to bolus
      flow.

PMID- 24917970
TI  - Effect of aspirin cessation before endoscopy in Japanese patients with low-dose
      aspirin-associated gastroduodenal mucosal injury.
AB  - BACKGROUND: The incidence of upper gastrointestinal injury by low-dose aspirin
      (LDA) has increased. OBJECTIVE: We aimed to clarify the risk factors and
      prevention strategies associated with LDA-induced gastroduodenal ulcer in
      Japanese patients. METHODS: A retrospective study involving 284 LDA users who
      underwent oesophagogastroduodenoscopy between January and December 2010 were
      included. We investigated the patients' clinical characteristics and endoscopic
      findings. RESULTS: Of 284 patients, 29 (10.2%) had gastro and/or duodenal ulcers.
      Male gender, peptic ulcer history, abdominal symptoms, half-dose proton pump
      inhibitors (PPIs), complete-dose PPIs, and nonsteroidal anti-inflammatory drugs
      were significantly associated with LDA-induced gastro and/or duodenal ulcers:
      odds ratio (95% confidence interval) 3.62 (1.06-12.27), 6.60 (1.84-23.62), 3.06
      (1.12-8.40), 0.16 (0.03-0.94), 0.07 (0.01-0.61), and 9.68 (1.64-57.18),
      respectively. PPI significantly reduced gastric ulcers and/or duodenal ulcers (p
      = 0.03). The modified Lanza score for gastric mucosal lesion in the LDA cessation
      group was significantly lower than in the LDA noncessation group (0.53 vs. 1.02;
      p = 0.008). CONCLUSIONS: Half-dose PPIs as well as complete-dose PPIs were
      effective for preventing LDA-induced gastric and/or duodenal ulcers. The
      cessation of LDA before endoscopy may lead to an underestimation of LDA-induced
      gastric injury.

PMID- 24917971
TI  - Hedgehog inhibition reduces angiogenesis by downregulation of tumoral VEGF-A
      expression in hepatocellular carcinoma.
AB  - BACKGROUND: Dysregulation and activation of Hedgehog (Hh) signalling may
      contribute to tumorigenesis, angiogenesis, and metastatic seeding in several
      solid tumours. OBJECTIVE: We investigated the impact of Hh inhibition on tumour
      growth and angiogenesis using in-vitro and in-vivo models of hepatocellular
      carcinoma (HCC). METHODS: The effect of the Hh pathway inhibitor GDC-0449 on
      tumour growth was investigated using an orthotopic rat model. Effects on
      angiogenesis were determined by immunohistochemical staining of von Willebrand
      factor antigen and by assessing the mRNA expression of several angiogenic
      factors. In vitro, HCC cell lines were treated with GDC-0449 and evaluated for
      viability and expression of vascular endothelial growth factor (VEGF).
      Endothelial cells were evaluated for viability, migration, and tube formation.
      RESULTS: In the orthotopic HCC model, GDC-0449 significantly decreased tumoral
      VEGF expression which was accompanied by a significant reduction of microvessel
      density and tumour growth. In HCC cells, GDC-0449 had no effect on cell growth
      but significantly reduced target gene regulation and VEGF expression while having
      no direct effect on endothelial cell viability, migration, and tube formation.
      CONCLUSIONS: Hh inhibition with GDC-0449 downregulates tumoral VEGF production in
      vitro and reduces tumoral VEGF expression, angiogenesis, and tumour growth in an
      orthotopic HCC model.

PMID- 24917972
TI  - Application of international consensus diagnostic criteria to an Italian series
      of autoimmune pancreatitis.
AB  - BACKGROUND: International consensus diagnostic criteria (ICDC) have been proposed
      to classify autoimmune pancreatitis (AIP) in type 1, type 2, or not otherwise
      specified. OBJECTIVE: Aim was to apply the ICDC to an Italian series of patients
      to evaluate the incidence and clinical profiles among different subtypes of AIP.
      METHODS: we re-evaluated and classified 92 patients diagnosed by Verona criteria,
      according to the ICDC. RESULTS: Out of 92 patients, 59 (64%) were diagnosed as
      type 1, 17 (18%) as type 2, and 15 (16%) as not otherwise specified according to
      the ICDC. A significant difference between type 1 and type 2 were found for age
      (54.5 +/- 14.5 vs. 34.4 +/- 13.9 respectively; p < 0.0001), male sex (76 vs. 47%;
      p = 0.007), jaundice (66 vs. 18%; p = 0.002) and acute pancreatitis (9 vs. 47%; p
      < 0.0001), elevated serum IgG4 levels (85 vs. 7%; p < 0.0001), inflammatory bowel
      disease (8 vs. 82%; < 0.0001), and relapse of the disease (34 vs. 6%; p = 0.058).
      Imaging and response to steroids in the not-otherwise-specified group were
      similar to type 1 and 2. CONCLUSIONS: Type 1 has a different clinical profile
      from type 2 autoimmune pancreatitis. The not-otherwise-specified group has
      peculiar clinical features which are shared both with type 1 or type 2 groups.

PMID- 24917973
TI  - Comparison of endosonography-guided vs. percutaneous biliary stenting when
      papilla is inaccessible for ERCP.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and biliary
      stenting fails in 5-10% patients of malignant biliary obstruction because papilla
      is inaccessible. Percutaneous transhepatic biliary drainage (PTBD) is an accepted
      alternative. Endosonography-guided biliary drainage (EUS-BD) has been described
      recently. AIM: To compare success rates and complications of EUS-BD and PTBD
      internal stenting. METHODS: This retrospective study included failed ERCP in
      inoperable malignant biliary obstruction due to inaccessible papilla undergoing
      PTBD or EUS-BD. Percutaneous transhepatic cholangiography guided/EUS-guided
      rendezvous procedures were excluded. When PTBD internal stenting failed, external
      drainage was performed. EUS-BD was performed using either intra- or extrahepatic
      approach, and stents were placed by transmural (choledocho-duodenostomy or
      hepatico-gastrostomy) or antegrade approach. Self-expandable metallic stents or
      plastic stents were placed in both groups. Success of internal stenting and
      complications were compared using t-test and chi-squared test. RESULTS:
      Retrospective review of 6 years of records (2005-2011) revealed 50 patients
      meeting the required criteria. EUS-BD was attempted in 25 and PTBD in 26 patients
      (one crossover from EUS-BD to PTBD). Internal stenting was technically and
      clinically successful in 23/25 (92%) EUS-BD vs. 12/26 (46%) PTBD (p < 0.05).
      External catheter drainage was performed in remaining 14 PTBD patients.
      Complications occurred in 5/25 (20%) EUS-BD (one major, four minor) and in 12/26
      (46%) PTBD (four major, eight minor; p < 0.05). Late stent occlusion occurred in
      one EUS-BD and three PTBD. CONCLUSIONS: In this retrospective study comparing
      success and complications of EUS-BD and PTBD in patients with inoperable
      malignant biliary obstruction and inaccessible papilla, EUS-BD was found superior
      to PTBD for both comparators.

PMID- 24917974
TI  - The impact of early endoscopic lesions on the clinical course of patients
      following ileocolonic resection for Crohn's disease: A 5-year prospective cohort
      study.
AB  - BACKGROUND: Early endoscopic lesions following resection for Crohn's disease (CD)
      are often observed. Currently, the relationship between this endoscopic
      observation and subsequent occurrence of CD lesions or recurrence is not
      understood well, but should be valuable in the context of predicting CD course.
      This prospective study was to investigate the impact of early endoscopic lesions
      on future clinical recurrence rates following ileocolonic resection for CD.
      METHODS: Forty patients who had maintained clinical remission, CD activity index
      (CDAI) <150 with mesalazine during 6 months after ileocolonic resection for CD
      were included. At 6 months after surgery, ileocolonoscopy was performed, and the
      endoscopic activity score at the proximal site of the anastomosis was determined
      according to Rutgeerts. All patients were regularly monitored for 5 years, and
      clinical recurrence was defined as CDAI >= 150. Corticosteroids,
      immunosuppressants, or biological agents were not given unless there was clinical
      recurrence. RESULTS: At 6 months after surgery, the endoscopic scores were i0 or
      i1 in 27 patients, i2 in seven patients, i3 in four patients, and i4 in two
      patients. During the following 5 years, the clinical recurrence occurred in three
      (11%) patients with endoscopic score of i0 or i1, four (57%) patients with i2
      score, three (75%) patients with i3 score, and two (100%) patients with i4 score,
      showing a significant positive correlation (p = 0.001) between the endoscopic
      severity of the proximal site of the anastomosis at 6 months after surgery and
      the clinical recurrence rate during the following 5 years. CONCLUSIONS: The
      assessment of endoscopic lesions at the proximal site of the anastomosis appeared
      to be valuable for predicting subsequent clinical recurrence after ileocolonic
      resection for CD. Further studies in larger cohorts of patients are warranted to
      strengthen our findings.

PMID- 24917975
TI  - UEG: What is the Public Affairs Committee (PAC)?

PMID- 24917976
TI  - UEG Week 2013: Scientific programme finalised and the top five abstracts selected
      by the Scientific Committee.

PMID- 24917977
TI  - Hot topics in gut microbiota.
AB  - The study of gut microbiota is a rapidly moving field of research, and the impact
      of gut microbial communities on human health is widely perceived as one of the
      most exciting advancements in biomedicine in recent years. The gut microbiota
      plays a key role in digestion, metabolism and immune function, and has widespread
      impact beyond the gastrointestinal tract. Changes in the biodiversity of the gut
      microbiota are associated with far reaching consequences on host health and
      development. Further understanding of the importance of developing and
      maintaining gut microbiota diversity may lead to targeted interventions for
      health promotion, disease prevention and management. Diet, functional foods and
      gut microbiota transplantation are areas that have yielded some therapeutic
      success in modulating the gut microbiota, and warrant further investigation of
      their effects on various disease states. 

PMID- 24917978
TI  - Serological testing for celiac disease in adults.
AB  - BACKGROUND AND AIM: We present a systematic review on the performance of
      currently available methods for serological diagnosis of celiac disease (CD) and
      the role of human leukocyte antigen (HLA) typing. OBJECTIVE: A literature survey
      was conducted using PubMed, MeSH database, Web of Science as well as manual
      searches. RESULTS: Tissue transglutaminase antibodies (tTG) (IgA) (tested in nine
      studies) show sensitivities and specificities in the range of 0.76-0.968 and
      0.909-0.98, and deamidated gliadin peptide (DGP) (IgA and IgG) (tested in eight
      studies) show sensitivities and specificities in the range of 0.69-0.984 and
      0.903-1. Endomysial antibodies (EMA) (tested in five studies) show sensitivities
      and specificities in the range of 0.61-0.937 and 0.98-1, respectively.
      Combination assays (tested in three studies) using DGP + tTG and DGP (IgA + IgG)
      show sensitivities and specificities in the range of 0.87-1 and 0.8-1,
      respectively. HLA DQ2/DQ8 may be necessary for the development of CD-HLA DQ2 in
      particular. A possible close correlation may also exist between CD and HLA-G.
      CONCLUSION: DGP and tTG for serological testing for CD show equivalent diagnostic
      performance. More studies with, in particular, DGP alone and in combination with
      tTG are necessary before a firm recommendation can be made. HLA typing to exclude
      CD may still be controversial. It still seems premature to diagnose celiac
      disease in adults based on serology alone.

PMID- 24917979
TI  - Endoscopic ultrasound, the one-stop shop for abdominal pain?
AB  - The Endosonography for Right Sided and Acute Upper Intestinal Misery (EFRAIM)
      study indicates that the yield of endoscopic ultrasound (EUS) is equivalent if
      not superior to upper endoscopy combined with transabdominal ultrasound in
      patients presenting with acute discomfort. Furthermore, this strategy may be more
      cost effective as EUS simultaneously enables assessment of intraluminal disease
      as well as extra intestinal pathology. These results are in sync with prior
      studies demonstrating the hegemony of EUS in the assessment of pancreaticobiliary
      disease and its role in the assessment of enigmatic chronic abdominal pain.
      Nevertheless, EUS does not permit assessment for appendicitis or genitourinary
      catastrophe. Thus a careful history and physical examination to localize pain to
      the right upper quadrant and epigastrium is essential. 

PMID- 24917980
TI  - Endosonography For Right-sided and Acute Upper Intestinal Misery: the EFRAIM
      study: A prospective, randomized, controlled, blinded study.
AB  - BACKGROUND: Acute upper abdominal pain is a frequent symptom leading to hospital
      admission. OBJECTIVE: To determine whether a primary intra- and extraluminal
      diagnostic approach enabled by endoscopic ultrasound is as effective as a
      conventional diagnostic algorithm of transabdominal ultrasound followed by
      oesophagogastroduodenoscopy. METHODS: A total of 240 patients who presented with
      acute right-sided and/or upper abdominal pain were prospectively recruited.
      Exclusion criteria were chronic pain, malignancy, prior abdominal surgery,
      bleeding, peritonitis, and elevated liver enzymes or lipase as defined 3-times
      higher than upper reference value. All patients underwent first transabdominal
      ultrasound and were then randomized (1 : 1) to either endoscopy followed by
      endoscopic ultrasound or vice versa. Patients and respective examiners were
      blinded to prior findings. RESULTS: A total of 223 patients were included.
      Endoscopic ultrasound provided a higher diagnostic yield than the combination of
      transabdominal ultrasound and endoscopy (62.3 vs. 50.7%; p = 0.001). For
      mucosal/intraluminal lesions, we observed a very good agreement between both
      endoscopic modalities (kappa 0.89). The agreement for pancreatic and biliary
      causes was good between both ultrasound modalities (kappa 0.66). CONCLUSIONS: Due
      to its high diagnostic yield, endoscopic ultrasound as a primary diagnostic
      modality appears to be a valuable option in patients with acute upper abdominal
      pain.

PMID- 24917981
TI  - The societal gain of medical development and innovation in gastroenterology.
AB  - BACKGROUND: Gastroenterology has over the past 30 years evolved very rapidly. The
      societal benefits to which this has led are incompletely determined, yet form a
      mandate to determine the need for future innovations and further development of
      the field. A more thorough understanding of societal benefits may help to
      determine future goals and improve decision making. AIMS: The objective of this
      article is to determine the societal gains of medical innovations in the field of
      gastroenterology in the past and future, using peptic ulcer disease as an example
      of past innovation and the implementation of colorectal cancer screening as an
      illustration of future gains. METHODS: Literature searches were performed for
      data on peptic ulcer and colorectal cancer epidemiology, treatment outcomes, and
      costs. National and governmental databases in the Netherlands were searched to
      obtain the input for calculations of quality-adjusted life years (QALYs), health
      adjusted life expectancy (HALE), and the corresponding societal benefit. RESULTS:
      Since 1980 the improvements in peptic ulcer treatment have had a limited impact
      on life expectancy, rising from 83.6 years to 83.7 years, but have led to a
      yearly gain of 46,000 QALYs, caused by improved quality of life. These
      developments in the field of peptic ulcer translated into a yearly gain of 1.8
      billion to 7.8 billion euros in 2008 compared with the 1980s. Mortality due to
      colorectal cancer is high, with 21.6 deaths per 100,000 per year in the
      Netherlands (European Standardized Rate (ESR)). The future implementation of a
      nationwide call-recall colorectal cancer screening by means of biennial fecal
      immunochemical testing (FIT) is expected to result in a 50%-80% mortality
      reduction and thus a gain of an estimated 35,000 life years per year,
      corresponding to 26,000 QALYs per year. The effects of the implementation of FIT
      screening can be translated to a future societal gain of 1.0 billion to 4.4
      billion euro. CONCLUSIONS: The innovations and developments in the field of
      gastroenterology have led to significant societal gains in the past three
      decades. This process will continue in the near future as a result of further
      developments. These calculations provide a template for calculations on the need
      for specialist training as well as research and implementation of new
      developments in our field.

PMID- 24917982
TI  - The influence of the speed of food intake on multichannel impedance in patients
      with gastro-oesophageal reflux disease.
AB  - BACKGROUND: There is a general belief that gastro-oesophageal reflux increases
      after meals and especially following a rapid intake. OBJECTIVE: To evaluate the
      impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD)
      patients. MATERIALS AND METHODS: Forty-six GORD patients with heartburn and / or
      acid regurgitation once a week or more often common were included in this study.
      Participants were asked to eat the same standard meal within either 5 or 30
      minutes under observation in a random order on 2 consecutive days. A total of 28
      hours of recording were obtained by intraoesophageal impedance pH and number of
      liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating
      postprandial periods were calculated. RESULTS: While all patients defined GORD
      symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance
      measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive
      oesophagitis. No difference has been shown according to the eating speed when all
      reflux episodes were taken together (754 vs. 733). Speed of food intake also did
      not have an impact on patients with normal vs. pathological 24-h intraoesophageal
      impedance or erosive vs. non-erosive. During the first postprandial hour,
      approximately half of the reflux events were non-acid, compared to 34.2% during
      the second hour and 26.8% during the third hour (p < 0.001). The number of acid
      reflux episodes was significantly higher than non-acid reflux especially during
      the second and third hours and in total for 3 hours. CONCLUSIONS: This first
      study addressing the effect of eating speed on reflux episodes in GORD patients
      did not support the general belief that reflux increases following fast eating.
      Acid and non-acid reflux were similar at the first postprandial hour, then acid
      reflux episodes were predominantly higher, which implicate the importance of acid
      pockets.

PMID- 24917983
TI  - Fibrolamellar hepatocellular carcinoma in the USA, 2000-2010: A detailed report
      on frequency, treatment and outcome based on the Surveillance, Epidemiology, and
      End Results database.
AB  - OBJECTIVE: Epidemiological and clinical information on fibrolamellar
      hepatocellular carcinoma (fHCC) is scarce. We performed a Surveillance,
      Epidemiology and End Results (SEER) database analysis with the aim of collecting
      information to better understand the biology and clinical aspects of this rare
      disease. DESIGN: Incidence trends, race- and age-specific rates, tumor size,
      first course surgery and five-year relative survival of 191 US cases (SEER)
      diagnosed with fHCC during 2000-2010 were compared to cases with hepatocellular
      carcinoma (HCC), HCC-not otherwise specified (HCC-NOS) and other HCC-types.
      RESULTS: While HCC-NOS incidence rates increased by 5.2% annually from 2000-2008
      (p < 0.05) before leveling, the 1.3% change in fHCC incidence was not
      statistically significant. The rates of fHCC were similar across ethnic groups
      while HCC-NOS incidence rates were higher among non-whites. Although 16% of fHCC
      patients had primary tumors <=5 cm compared to 37% of HCC-NOS cases five-year
      survival was better among fHCC (34%) than HCC-NOS cases (16%). Fibrolamellar HCC
      cases of 0-39 years of age were more likely to receive radiofrequency ablation,
      transplant or resection than HCC-NOS cases of that age. Survival was similar
      among fibrolamellar and HCC-NOS cases receiving surgery. CONCLUSION: In this
      largest case series, fibrolamellar and HCC-NOS age- and race-specific incidence
      rates and time trends differed. Despite larger tumor size than HCC-NOS cases
      fibrolamellar cases received surgery more often and had better survival rates.
      Differences in co-morbidity may influence treatment. Studies of fHCC biology,
      including by age, are recommended.

PMID- 24917984
TI  - Symptom pattern following a meal challenge test in patients with irritable bowel
      syndrome and healthy controls.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) often complain of
      worsening of symptoms after meal intake. Meal challenge tests have previously
      been used to study symptoms and pathophysiology in functional dyspepsia.
      OBJECTIVE: The objective of this article is to evaluate differences in
      gastrointestinal (GI) symptom response to a standardized meal test in IBS
      compared to healthy controls. METHODS: We included 67 patients with IBS and 16
      healthy controls. After an overnight fast the subjects were served breakfast (540
      kcal; 36% fat, 15% proteins, 49% carbohydrates; 8.9 g fiber). They completed
      visual analog scales assessing severity of six GI symptoms (abdominal pain,
      bloating, discomfort, nausea, gas, fullness) before breakfast and every 30
      minutes up to 240 minutes after breakfast. The patients also completed a
      questionnaire (IBS-SSS) to assess IBS symptom severity during the preceding week.
      The course of symptom scores over time was analyzed using mixed models. RESULTS:
      The meal was well tolerated and all subjects completed the test period. In
      patients, significant effects of time (initial increase to a maximum, followed by
      a return to baseline) were found for fullness, bloating, nausea and discomfort
      (all p values < 0.01 for linear, quadratic and third-order effect of time). In
      IBS patients, an independent significant association between IBS-SSS scores and
      all postprandial symptoms, except for nausea, was found (all p < 0.01). In
      controls, a significant linear, quadratic and third-order effect of time (all p <
      0.0001) was found for fullness only. The difference in time course for bloating
      and discomfort between IBS patients and controls was confirmed when comparing the
      groups directly (significant time-by-group interaction effects, all p < 0.05),
      but not for nausea. On average, IBS patients scored significantly higher than
      controls on all symptoms, except for nausea (significant main effects of group,
      all p < 0.05). CONCLUSIONS: A standardized meal test seems to be a promising tool
      to study the symptom pattern in IBS and potentially to follow the effect of
      interventions.

PMID- 24917985
TI  - Faecal calprotectin and lactoferrin as markers for monitoring disease activity
      and predicting clinical recurrence in patients with Crohn's disease after
      ileocolonic resection: A prospective pilot study.
AB  - BACKGROUND: Several studies have reported that faecal calprotectin and
      lactoferrin showed a close correlation with endoscopic inflammation in patients
      with inflammatory bowel disease. However, the clinical significance of faecal
      calprotectin or lactoferrin in postoperative Crohn's disease (CD) is not fully
      evaluated. This prospective study was to investigate the relationship between
      endoscopic activity, and faecal calprotectin and lactoferrin, and assess the
      predictive value of these markers for future recurrence. METHODS: Twenty patients
      who remained in remission during 6-12 months after ileocolonic resection for CD
      were included. All patients underwent ileocolonoscopy for assessing endoscopic
      activity (Rutgeerts score) in the neo-terminal ileum. A stool sample was
      collected for measurement of calprotectin and lactoferrin. All patients were then
      followed up for 12 months, and clinical recurrence was defined as a CDAI >150
      with an increase of >=70 points. RESULTS: The mean time between surgery and the
      endoscopic examination at entry was 7.2 months. The endoscopic scores were i0 or
      i1 in 10 patients, i2 in six patients, i3 in three patients, and i4 in one
      patient. Both calprotectin and lactoferrin positively correlated with the
      endoscopic scores (p = 0.0001 and p = 0.038, respectively). Six patients
      developed clinical recurrence during the 12-month follow-up. Both calprotectin
      and lactoferrin levels were significantly higher in patients with clinical
      recurrence than those in remission (p = 0.0007 and p = 0.025, respectively). A
      cutoff value of 170 ug/g for calprotectin had a sensitivity of 83% and a
      specificity of 93% to predict a risk of clinical recurrence, while a cutoff value
      of 140 ug/g for lactoferrin had a sensitivity of 67% and a specificity of 71%.
      CONCLUSIONS: Both calprotectin and lactoferrin levels correlate well with
      endoscopic activity after ileocolonic resection for CD. Calprotectin and
      lactoferrin could be clinically relevant biomarkers for predicting postoperative
      recurrence. Further well-designed large trials should strengthen the findings of
      the present investigation.

PMID- 24917986
TI  - Factors affecting satisfaction with treatment in European women with chronic
      constipation: An internet survey.
AB  - BACKGROUND: Data on factors affecting treatment satisfaction in European women
      with chronic constipation are limited. OBJECTIVE: To assess factors associated
      with treatment satisfaction among European women with chronic constipation.
      METHODS: A 2011-2012 internet survey was conducted in men and women from 12
      European countries. Respondents analysed were female with self-reported chronic
      constipation (>=1 symptoms for >=6 months of lumpy/hard stools, feeling of
      incomplete evacuation, and pain during defecation, as well as <3 bowel
      movements/week). For laxative users, satisfaction with treatment, factors
      affecting satisfaction, and interactions with healthcare professionals were
      collected. RESULTS AND CONCLUSIONS: In total, 4805/50,319 participants fulfilled
      the inclusion criteria (female with chronic constipation). Of the laxative users
      (1575/4805), 57% (n = 896) were satisfied with their treatment, while 26% were
      neutral, and 17% dissatisfied. Dissatisfied respondents visited their GP less
      frequently in the past 12 months, were more likely to obtain over-the-counter
      laxatives, and took a dose higher than recommended more frequently than those
      satisfied. Respondents were most satisfied with ease of use of treatment and
      least satisfied with relief from bloating. Newer treatments aimed at alleviating
      symptoms, particularly bloating, are required for respondents neutral or
      dissatisfied with their current treatment.

PMID- 24917987
TI  - A survey of pharmacological and nonpharmacological treatment of functional
      gastrointestinal disorders.
AB  - BACKGROUND: Treatment of functional gastrointestinal disorders (FGIDs) is based
      on symptoms relieve by conventional drugs, but increasingly complementary and
      alternative medicine (CAM) is used. OBJECTIVE: This survey aimed to investigate
      the current treatments used by FGIDs patients. METHODS: A total of 25 Italian
      gastroenterologists interviewed outpatients on gastrointestinal symptoms and
      treatments (pharmacological, CAM, diet/dietary supplements) used during the last
      year to relieve FGIDs. Consecutive adults with FGIDs according to Rome III were
      included. RESULTS: Of the 199 patients, 81% used conventional drugs, 64.3%
      diet/dietary supplements, and 48.7% CAM. Conventional drugs, diet/dietary
      supplements, or CAM as exclusive treatment were used by 24.6, 6, and 2.5% of
      patients, respectively. Two-thirds used more than one treatment: 34.7%
      conventional drugs, CAM, and diet/dietary supplements, 17.1% conventional drugs
      and diet/dietary supplements, 10.1% diet and CAM, and 5% conventional drugs and
      CAM. Benefits and adverse effects were similar for conventional drugs and
      nonpharmacological treatments. Males (OR 2.4) without lower GI symptoms (OR 5.4)
      used more frequently exclusive pharmacological treatment of FGIDs. CONCLUSIONS:
      Conventional drugs are the preferred treatment for FGID. CAM and dietary
      modifications are more likely used as an adjunct to rather than instead of
      conventional drugs. Adverse effects occurred in all treatments.

PMID- 24917989
TI  - UEG Week Vienna 2014: New horizons, fresh ideas.

PMID- 24917988
TI  - Early life factors initiate a 'vicious circle' of affective and gastrointestinal
      symptoms: A longitudinal study.
AB  - OBJECTIVE: Functional gastrointestinal disorders (FGID) have been shown to be
      associated with both comorbid mood disorders and traumatic events such as abuse
      earlier in life. In a longitudinal study, we tested a model that hypothesized:
      (i) childhood abuse was associated with subsequent mood disorder and pain or
      interference in life by bowel symptoms both directly and indirectly via neurotic
      personality; and (ii) an ongoing cycle of mood disorder impacts on bowel
      symptoms. DESIGN: Subjects from the general population classified as irritable
      bowel syndrome and/or functional dyspepsia (IBS/FD, n = 207) or free of FGID (n =
      100) were prospectively studied every 6 months over 18 months. In addition to
      bowel symptom interference and abdominal pain, measures of personality
      (neuroticism), childhood abuse history, depression, and anxiety were obtained.
      The hypothesized model was tested via Path Modelling. RESULTS: Childhood abuse
      was found to be directly associated with neuroticism but only indirectly
      associated with baseline interference and mood disorders (via neuroticism). The
      data further supported an ongoing cycle of elevations in mood disorders and
      pain/interference by bowel symptoms. The data supported direct effects of
      interference at one time point on interference at the subsequent time point in
      addition to indirect effects of prior anxiety and depression. Repeating the model
      with pain frequency as the outcome yielded almost identical findings which
      suggests the findings are generalized across domains of symptoms and quality-of
      life. CONCLUSION: Our data provide support for a model characterized by a
      'vicious circle' between mood disorders and FGID symptoms in adulthood, with
      initial input from early life factors.

PMID- 24917990
TI  - Learn it by doing it! Hands on education at UEG.

PMID- 24917991
TI  - Gastrointestinal motility revisited: The wireless motility capsule.
AB  - INTRODUCTION: The wireless motility capsule (WMC) is a novel ambulatory
      technology that concurrently measures intraluminal pH, temperature, and pressure
      as it traverses the gastrointestinal tract. OBJECTIVES: We aim to provide a
      concise summary of the WMC, detailing the procedure for its administration and
      the parameters it records. We also review the evidence that has validated the WMC
      against other methods currently regarded as 'gold standard'. CONCLUSIONS: The WMC
      offers a number of advantages over and above current techniques, especially with
      respect to patient tolerability, safety, and standardization. The WMC represents
      a considerable enhancement of the researchers' and clinicians' investigatory
      armamentarium. If this technology becomes widely adopted, coupled with
      international consensus upon the interpretation of physiological data derived
      therein, it may herald a new and exciting era in gastrointestinal physiology.

PMID- 24917992
TI  - The good lies so near - in vivo diagnosis of colonic polyps.

PMID- 24917993
TI  - High-definition vs. standard-definition endoscopy with indigo carmine for the in
      vivo diagnosis of colonic polyps.
AB  - BACKGROUND: There is growing evidence that indigo carmine chromoendoscopy is
      effective for the in vivo diagnosis of colonic polyps. However, the impact of
      colonoscope resolution on diagnostic accuracy has not been investigated.
      OBJECTIVE: We aimed to compare the effectiveness of in vivo diagnosis of small
      colonic polyps using indigo carmine dye spray with standard-definition and high
      definition colonoscopes. METHODS: Procedures were performed using Fujinon
      colonoscopes and EPX 4400 processor. Fujinon standard-definition (SD) and high
      definition (HD) colonoscopes were used, with the endoscopist blinded to
      colonoscope definition. Polyps <10 mm were assessed using 0.2% indigo carmine dye
      spray, with the predicted diagnosis recorded. In each case the kind of
      colonoscope (SD or HD) was recorded. Polyps were removed and sent for
      histological analysis, with the pathologist blinded to the diagnosis made by the
      endoscopist. The predicted diagnosis was compared with the true histology to
      calculate the accuracy, sensitivity and specificity of in vivo assessment using
      either SD or HD scopes. RESULTS: In total 237 polyps <10 mm in size were
      examined. There was no statistically significant difference for any of the
      measured parameters between SD and HD assessments, with an accuracy, sensitivity
      and specificity of 89%, 91% and 87% with SD colonoscopes and 92%, 96% and 84%
      with HD colonoscopes. CONCLUSIONS: The accuracy of in vivo assessment of small
      colonic polyps with indigo carmine dye spray is excellent with standard
      definition colonoscopes and is not improved with high-definition colonoscopes.

PMID- 24917994
TI  - Cigarette smoking is a modifiable risk factor for Barrett's oesophagus.
AB  - BACKGROUND: Cigarette smoking has been associated with an increased risk of
      oesophageal adenocarcinoma (OAC). However, the impact of smoking and more
      importantly smoking cessation on Barrett's oesophagus (BO) is unclear. OBJECTIVE:
      The aim of the study is to evaluate the association between cigarette smoking and
      presence of BO in a large prospective cohort of patients with gastro-oesophageal
      reflux disease (GORD). METHODS: Patients presenting to the endoscopy unit for
      upper endoscopy completed a validated GORD questionnaire and information on
      demographics (age, gender, and ethnicity), cigarette smoking [status
      (current/past), amount (pack years) and duration of smoking cessation], clinical
      data [medication history, body mass index (BMI), and family history] and
      endoscopic findings [BO and hiatal hernia] were recorded. Cigarette smokers
      (current and past) and nonsmokers were compared using Fisher's Exact test for
      categorical variables and Mann-Whitney test for continuous variables. Effects of
      cigarette smoking and smoking cessation on BO risk was assessed by stepwise
      logistic regression analysis. RESULTS: A total of 1056 patients were included in
      the analysis [mean age: 57.2 +/- 12.7years, Caucasian 880 (83.3%), male 985
      (93.3%), and mean BMI 29.6 (SD: +/- 5.6)]. 827 (78.3%) were smokers and 229
      (21.6%) were nonsmokers. 474 subjects (44.9%) had a previous history of smoking.
      Anytime smokers were more likely to have BO (adjusted OR: 3.3; 95 CI: 1.7-6.3; p
      < 0.01). Higher smoking burden (pack years) was associated with higher risk of BO
      in this GORD cohort (p for trend < 0.01). Duration of smoking cessation was
      inversely associated with risk of BO (p for trend: 0.01). CONCLUSION: This study
      shows that smokers with reflux symptoms have about threefold higher risk of BO
      compared with nonsmokers, whereas discontinuing smoking is associated with a
      significant reduced risk. Smoking cessation appears to be a viable option to
      reduce BO risk in patients with reflux disease.

PMID- 24917995
TI  - Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux
      events: A study with oesophageal and pharyngeal pH-impedance monitoring.
AB  - BACKGROUND: Pharyngeal pH probes and pH-impedance catheters have been developed
      for the diagnosis of laryngo-pharyngeal reflux. OBJECTIVE: To determine the
      reliability of pharyngeal pH alone for the detection of pharyngeal reflux events.
      METHODS: 24-h pH-impedance recordings performed in 45 healthy subjects with a
      bifurcated probe for detection of pharyngeal and oesophageal reflux events were
      reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous
      occurrence of pharyngeal reflux, gastro-oesophageal reflux, and swallows,
      according to impedance patterns. RESULTS: Only 7.0% of pharyngeal pH drops to
      below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6%
      were related to swallows and 10.2 and 13.3% were associated with proximal and
      distal gastro-oesophageal reflux events, respectively. Of pharyngeal pH drops to
      below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows,
      and 18.1 and 21.5% were associated with proximal and distal gastro-oesophageal
      reflux events, respectively. CONCLUSIONS: This study demonstrates that pharyngeal
      pH alone is not reliable for the detection of pharyngeal reflux and that adding
      distal oesophageal pH analysis is not helpful. The only reliable analysis should
      take into account impedance patterns demonstrating the presence of pharyngeal
      reflux event preceded by a distal and proximal reflux event within the
      oesophagus.

PMID- 24917996
TI  - Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF
      study): A multicentre, prospective, randomized, double-blind, placebo-controlled
      clinical trial.
AB  - BACKGROUND: Since the publication of the Rome III criteria for functional
      dyspepsia (FD), the evidence about the efficacy of half-dose of proton pump
      inhibitors for dyspepsia symptoms have been limited. OBJECTIVE: To examine the
      efficacy of lansoprazole for functional dyspepsia (FD) diagnosed with the Rome
      III criteria by the multicentre, double-blind, randomized, placebo-controlled
      study in Japan. METHODS: A total of 54 FD participants were randomized to
      lansoprazole 15 mg once daily or placebo for a 4-week double-blind treatment
      period. The primary efficacy endpoint was an overall dyspeptic symptom relief
      rate evaluated by 5-point Likert scale scores. The alteration of dyspeptic
      symptom scores during the study period was also assessed. RESULTS: At week 4, the
      overall dyspeptic symptom relief rates were higher in the lansoprazole group
      (30.4%) than in the placebo group (6.7%) (p = 0.045). The scores for epigastric
      pain (p = 0.045) and epigastric burning (p = 0.03) were significantly improved in
      the lansoprazole group compared to the placebo group, whereas the improvement of
      the scores for postprandial fullness (p = 0.81) and early satiation (p = 0.33)
      was not different between lansoprazole and placebo groups. CONCLUSIONS:
      Lansoprazole 15 mg ameliorates dyspeptic symptoms, particularly the epigastric
      pain syndrome-related symptoms of FD.

PMID- 24917997
TI  - Endoscopic submucosal dissection for early gastric cancer in cases preoperatively
      contraindicated for endoscopic treatment.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is an optimal
      treatment for early gastric cancer (EGC) with negligible risk of lymph node
      metastasis; however, ESD is sometimes performed to treat lesions preoperatively
      contraindicated for the procedure due to various reasons. Here we aim to evaluate
      the treatment outcomes of ESD for lesions that were preoperatively
      contraindicated for ESD. PATIENTS AND METHODS: Clinicopathological data of 104
      EGC lesions in 104 patients were reviewed retrospectively. The demographic
      characteristics of patients, reasons for ESD, treatment results, complications,
      and outcomes were assessed. RESULTS: The major reasons for undergoing ESD
      included advanced age, desire to undergo ESD, and the existence of comorbidities.
      En-bloc and complete resection rates were 97 and 71%, respectively. Perforation
      and postoperative bleeding rates were 13 and 9%, respectively. Resection was
      beyond the expanded Japanese criteria for endoscopic treatment of EGC in 87
      patients (84%), 41 (47%) of whom underwent additional therapy, including
      subsequent gastrectomy (29 patients) and photodynamic therapy (12 patients). The
      median follow-up period was 47 months, during which seven patients died from
      recurrent disease. The 5-year overall and disease-specific survival rates were 70
      and 91.5%, respectively. CONCLUSIONS: ESD is a technically demanding procedure
      for lesions preoperatively contraindicated for endoscopic resection. The curative
      resection rate was low, but the 5-year disease-specific survival rate of 91.5%
      was favourable. In experienced hands, ESD may be a treatment option for patients
      not suitable for radical surgery, and the relevant risk of complications must be
      considered before treatment.

PMID- 24917998
TI  - Capsule endoscopy: High negative predictive value in the long term despite a low
      diagnostic yield in patients with suspected Crohn's disease.
AB  - INTRODUCTION: The role of small bowel capsule endoscopy (SBCE) in Crohn's disease
      (CD) has expanded with greater understanding of the technology. The ability of
      SBCE to differentiate CD from other causes of inflammation has been questioned.
      Longitudinal studies are required to assess the long-term impact and significance
      of SBCE findings in suspected CD. This study aimed to determine the long-term
      clinical accuracy of SBCE in patients referred with suspected CD. METHODS: A
      retrospective review was carried out on SBCE procedures performed for suspected
      CD since 2010. Only patients with at least 6 months of documented follow up were
      included. A chart review was undertaken to record SBCE findings/correlate with
      subsequent diagnosis and outcome. RESULTS: In all, 95 patients with sufficient
      follow up were identified. The mean follow up was 13 months (range 8-24). In
      total, 72 (76%) SBCEs were negative and 23 (24%) positive for CD. Of the 72
      negative tests, two patients (3%) were later diagnosed with CD. The negative
      predictive value is 96%. There was a strong positive correlation between results
      of WCE and subsequent clinical diagnosis. CONCLUSIONS: SBCE appears capable of
      safely out-ruling CD, with only 3% of negative SBCE investigations being
      diagnosed with CD after 15 months.

PMID- 24918000
TI  - New research findings in gastroenterology have been presented at UEG Week 2013 in
      Berlin.

PMID- 24918001
TI  - Survey of Digestive Health across Europe.

PMID- 24917999
TI  - CD25 and TNF receptor II reflect early primary response to infliximab therapy in
      patients with ulcerative colitis.
AB  - BACKGROUND: Although infliximab treatment is an option for patients with
      ulcerative colitis (UC), not all patients do respond to therapy, and cellular
      mechanisms leading to therapy response are incompletely known. OBJECTIVE: The
      objective of this article is to determine early effects of infliximab therapy on
      T cells in the blood of UC patients and if effects differed in therapy responders
      and nonresponders. METHODS: Blood samples were obtained before and two weeks post
      treatment start from 34 anti-tumor necrosis factor (TNF) therapy-naive UC
      patients undergoing infliximab therapy. Response to therapy was evaluated prior
      to the fourth treatment dose. Expression of T cell surface markers and levels of
      soluble receptors and cytokines in serum were determined. RESULTS: At baseline,
      there were no differences in cellular, biochemical or clinical parameters between
      therapy responders and nonresponders. Infliximab therapy reduced frequencies of
      CD25(+) T cells and increased frequencies of annexin V(+) T cells in patients
      responding to infliximab, but not in nonresponding patients, two weeks after
      therapy start. Only therapy responders had decreased serum levels of sCD25 and
      sTNFRII two weeks after treatment start. In contrast, clinical parameters did not
      reflect therapy outcome already two weeks after therapy start. CONCLUSION:
      Soluble and membrane-bound T cell receptors may be early indicators of infliximab
      therapy response in UC, which can be of clinical importance for the decision when
      to continue or to stop the treatment.

PMID- 24918003
TI  - Fructose-induced symptoms beyond malabsorption in FGID.
AB  - The dietary carbohydrate fructose can be incompletely absorbed in the small
      intestine and is sometimes associated with gastrointestinal symptoms that include
      motility disturbances and abdominal pain. Fructose malabsorption has been well
      documented in variable but similar proportions of healthy and populations with
      functional gastrointestinal disorders. Recent work into the expression of the
      main intestinal fructose transporter proteins highlight that our understanding of
      the mechanistic basis for fructose malabsorption and how it differentiates in
      gastrointestinal patients is incomplete. Until we have further mechanistic
      insight, restricting dietary fructose intake and other poorly absorbed short
      chain carbohydrates and polyols remains an efficacious approach for managing
      functional gastrointestinal symptoms. 

PMID- 24918002
TI  - Timing of endoscopy in gastrointestinal bleeding.
AB  - BACKGROUND: In gastrointestinal bleeding, a physician often has to make a
      decision between two possible choices. Endoscopic management of the bleeding
      could be initiated immediately, or it could be delayed until the patient has
      become haemodynamically stable or the conditions for a successful endoscopy have
      otherwise improved. OBJECTIVE: The present article serves to present such
      situations and highlights their characteristic features. METHODS: The choice
      between immediate and delayed endoscopy is analysed in terms of a decision tree,
      comparing the expected results of the two management alternatives. The decision
      tree is applied to three different clinical scenarios associated with
      gastrointestinal bleeding, where performing endoscopy later rather than sooner
      represents the preferred management option. RESULTS: The work up of chronic iron
      deficient anaemia in patients with serious cardiac problems should be deferred
      until resolution of their reduced cardiovascular status. It is also recommended
      that, even in acute bleeding, endoscopy is deferred until the patient has become
      haemodynamically stable. Lastly, for nonemergency treatment of oesophageal
      varices bleeding, a long rather than short interval between consecutive banding
      sessions appears more beneficial. CONCLUSIONS: The results illustrate how to use
      threshold analysis as a simple bedside tool to solve seemingly complex decisions
      associated with management of gastrointestinal bleeding.

PMID- 24918004
TI  - Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose
      intolerance.
AB  - BACKGROUND: Gastrointestinal symptoms and malabsorption following fructose
      ingestion (fructose intolerance) are common in functional gastrointestinal
      disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be
      related an abnormality of intestinal fructose transporter proteins. OBJECTIVE: To
      assess the expression of the main intestinal fructose transporter proteins,
      glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID. METHODS: The
      expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue
      was investigated using real-time reverse-transcription PCR and Western
      immunoblotting in 11 adults with FGID and fructose intolerance ascertained by
      breath testing and in 15 controls. RESULTS: Median expression levels of GLUT5
      mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13-0.21) in
      patients and 0.17 (IQR 0.12-0.19) in controls (p > 0.05). Respective levels of
      GLUT2 mRNA were 0.26 (IQR 0.20-0.31) and 0.26 (IQR 0.19-0.31) (p > 0.05). Median
      expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR
      0.52-1.68) in patients and 0.95 (IQR 0.59-1.15) in controls (p > 0.05).
      Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06-2.14) and 1.35
      (IQR 0.96-1.79) (p > 0.05). CONCLUSIONS: Human fructose intolerance may not be
      associated with marked changes in GLUT5 and GLUT2 expression. Replication of
      these results in a larger subject group, including measures of transporter
      activation and membrane and subcellular localization, is warranted.

PMID- 24918005
TI  - Factors related to bowel cleansing failure before colonoscopy: Results of the
      PACOME study.
AB  - BACKGROUND: The factors associated with inadequate bowel cleansing leading to
      colonoscopy failure are not well known. OBJECTIVE: We conducted a multicentre,
      prospective, observational case-control study in order to identify these factors.
      METHODS: Investigators included one patient with colonoscopy failure due to
      inadequate bowel cleansing (failure group) and the following patient with
      complete colonoscopy (success group). Data related to demographics, medical
      history, and preparation were collected and compared. Factors associated with
      bowel cleansing failure were identified by multivariate logistical regression
      analysis. RESULTS: A total of 101 gastroenterologists included 202 patients from
      1 November 2009 to 15 January 2010. There was no difference between both groups
      with regards to baseline characteristics. In univariate analysis, factors
      significantly associated with bowel cleansing failure were vomiting during
      preparation (p = 0.0007), incomplete intake of the preparation (p = 0.002), and
      constipation (p = 0.02). Type and timing of preparation were not significantly
      different between groups. In multivariate analysis, incomplete intake of the
      preparation (OR 4.5, 95% CI 1.2-17.3), constipation (OR 4.2, 95% CI 1.2-14.9),
      and treatment with neuroleptics or antidepressants (OR 9.9 (95% CI 1.4-71.0) were
      independent predictors of colonoscopy failure. CONCLUSIONS: Factors associated
      with bowel cleansing failure were incomplete intake of the preparation,
      constipation, and treatment with psychotropic drugs. Interventions to reduce poor
      colonoscopy preparations should be targeted at these at-risk patients.

PMID- 24918006
TI  - Comparison of six different calprotectin assays for the assessment of
      inflammatory bowel disease.
AB  - BACKGROUND AND OBJECTIVES: Faecal calprotectin is a valuable noninvasive marker
      for inflammatory bowel disease (IBD). The aim of our study was to determine the
      correlation between six different calprotectin assays and compare their
      performance for diagnosis and follow up of IBD. METHODS: Thirty-one patients with
      suspected IBD and 31 patients in follow up were included. We determined
      calprotectin by means of three rapid immmunochromatographic tests, two enzyme
      linked immunosorbent assays, and one automated fluoroimmunoassay. Results were
      correlated with endoscopic and histological findings. RESULTS: Although all
      methods correlated significantly, slopes and intercepts differed extensively,
      with up to 5-fold quantitative differences between assays. Sensitivity and
      specificity for diagnosis of IBD were 82-83 and 84-89%, respectively. For follow
      up, sensitivity in detecting mild ulcerative colitis was 71-100%. In moderate-to
      severe ulcerative colitis, sensitivity was 100% for all assays. Specificity was
      67-86% in both subgroups. In Crohn's disease, only moderate-to-severe disease
      could be differentiated from remission, with sensitivity 83-86% and specificity
      75% for all tests. CONCLUSIONS: All calprotectin assays showed comparable
      clinical performance for diagnosis of IBD. For follow up, performance was
      acceptable, except for mild Crohn's disease. Because of the large quantitative
      differences, further efforts are needed to standardize calprotectin assays.

PMID- 24918007
TI  - Clinical and genetic factors predicting response to therapy in patients with
      Crohn's disease.
AB  - AIM: To identify clinical and/or genetic predictors of response to several
      therapies in Crohn's disease (CD) patients. METHODS: We included 242 patients
      with CD (133 females) aged (mean +/- standard deviation) 39 +/- 12 years and a
      disease duration of 12 +/- 8 years. The single-nucleotide polymorphisms (SNPs)
      studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9
      C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with
      real-time PCR with Taqman probes. RESULTS: Older patients responded better to 5
      aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03,
      p = 0.01, respectively) while younger ones responded better to biologicals (OR
      0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA
      compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p =
      0.04). In respect to genetic predictors, we observed that heterozygotes for
      ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids
      (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of
      responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR
      0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of
      responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A
      SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a
      lower chance of responding to biologicals (OR 0.31, p = 0.07), which became
      significant after adjusting for gender (OR 0.75, p = 0.005). CONCLUSIONS: In the
      present study, we were able to identify a number of clinical and genetic
      predictors of response to several therapies which may become of potential utility
      in clinical practice. These are preliminary results that need to be replicated in
      future pharmacogenomic studies.

PMID- 24918009
TI  - Time to prepare and submit your abstract for UEG Week Vienna 2014.

PMID- 24918008
TI  - Welcome from the UEG President.

PMID- 24918010
TI  - Lack of seasonal variation in the incidence of eosinophilic oesophagitis in
      adolescent and adult non-PPI-responsive oesophageal eosinophilia midwestern US
      populations.
AB  - BACKGROUND: Eosinophilic oesophagitis (EoO) has been associated with allergic
      disorders as well as aeroallergens. The current literature has shown a possible
      association between seasonal variation, mainly in the spring, and the incidence
      of EoO. However, this data was based on small population studies that did not
      exclude proton-pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-ROE)
      in their cohort. AIM: The aim of this study was to determine if there is a
      seasonal variation associated with the diagnosis of EoO in patients that had been
      treated with high-dose PPI prior to diagnosis. METHODS: Oesophageal biopsies were
      obtained from a cohort of patients who presented with symptoms of dysphagia,
      odynophagia, and heartburn during a 10-year period. Symptomatic patients who had
      biopsies from the mid and distal oesophagus with >=20 eosinophils per high-power
      field (hpf) while on high-dose PPI treatment for at least 5 weeks were diagnosed
      as having EoO. The monthly and seasonal incidences were determined (winter,
      January-March; spring, April-June; summer, July-September; Autumn, October
      December). RESULTS: A total of 20,718 patients were identified and their records
      evaluated. From this cohort, 193 (0.93%) symptomatic patients had biopsy-proven
      oesophageal eosinophilia (>=20 eosinophils/hpf) and no seasonal variation was
      seen in this group. However, only 57 (0.28%) had been adequately treated with PPI
      prior to diagnosis (i.e. non-PPI-ROE biopsy-proven EoO; >=20 eosinophils/hpf: 39
      males, 18 females; age 29.5 years). The most common medical history components
      included asthma (12.3%) and food allergies (3.5%), and the most common presenting
      symptoms included dysphagia (50.9%) and heartburn (26.3%). The monthly and
      seasonal incidences in our cohort were with no apparent trend (p = 0.713 and
      0.703, respectively). CONCLUSIONS: The incidence of EoO was consistent across all
      12 months as well as during the four seasons. Our data does not support a
      seasonal variation in relation to the incidence of EoO in the US midwestern non
      PPI-ROE population.

PMID- 24918011
TI  - EndoFLIP system for the intraoperative evaluation of peroral endoscopic myotomy.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) has been recently introduced in
      clinical practice for the treatment of achalasia. The endoluminal functional
      lumen imaging probe (EndoFLIP) system) uses impedance planimetry for the real
      time measurement of the diameter of the oesophago-gastric junction. OBJECTIVE:
      The aim of this study is to prospectively evaluate the effect of POEM on the
      oesophago-gastric junction using EndoFLIP. METHODS: All the patients who
      underwent POEM in a single centre between April and July 2013 were enrolled in
      the study. EndoFLIP was used intraoperatively, immediately before and after POEM.
      During follow-up patients underwent oesophagogastroduodenoscopy, oesophageal pH
      monitoring and manometry. Clinical outcomes were compared with the diameter of
      the oesophago-gastric junction after POEM. RESULTS: In total, 23 patients (12
      males, mean age 51.7 years) were enrolled, and 21 underwent POEM successfully.
      Preoperative mean basal lower oesophageal sphincter pressure was 42.1 mmHg (+/
      17.6). Before POEM, the mean oesophago-gastric junction diameter and cross
      sectional area were 6.3 mm (+/-1.8) and 32.9 mm(2) (+/-23.1), respectively. After
      treatment, the mean diameter and cross-sectional area of the oesophago-gastric
      junction were 11.3 mm (+/-1.7 SD) and 102.38 mm(2) (+/-28.2 SD), respectively. No
      complications occurred during a mean follow-up of 5 months. Median post-operative
      Eckardt score was 1. Three patients (14.3%) referred heartburn. Follow-up studies
      revealed gastro-oesophageal reflux disease (GORD) in 57.1% of patients and
      oesophagitis in 33.3%. No correlations were observed between the diameter of
      oesophago-gastric junction after POEM and symptoms relief, GORD incidence and
      lower oesophageal sphincter pressure. CONCLUSIONS: The diameter of oesophago
      gastric junction substantially increases after POEM. EndoFLIP is a reliable
      method for the intraoperative evaluation of oesophago-gastric junction diameter.
      However, the real usefulness of this technology after POEM remains controversial.

PMID- 24918012
TI  - Rapid air infusion into the oesophagus: Motor response in patients with achalasia
      and nonobstructive dysphagia assessed with high-resolution manometry.
AB  - BACKGROUND: Achalasia is a neurodegenerative disorder of the oesophagus.
      Alteration of motor activity induced by oesophageal distension has not been
      explored. OBJECTIVES: To investigate this function, using high-resolution
      Manometry. METHODS: This study enrolled 15 healthy subjects, 15 nonobstructive
      dysphagia (NOD), and 18 achalasia patients successfully treated with pneumatic
      dilation (six with restored peristalsis). The three groups underwent five rapid
      (<1 s) intraoesophageal infusions of 20-ml air boluses, followed by eight 5-ml
      water swallows. RESULTS: WHEREAS THE RESPONSE RATE TO WATER SWALLOWS WAS SIMILAR
      IN THE THREE GROUPS, AIR INFUSION INDUCED A LOWER RESPONSE RATE IN ACHALASIA
      (MEDIAN, INTERQUARTILE RANGE: 70%, 40-100%) and, to a lesser extent, in NOD
      patients (100%, 60-100%) than in healthy subjects (100%, 100-100%; p < 0.001 and
      p = 0.06, respectively). However, the response rate was highly variable in
      achalasia patients irrespective of presence of peristalsis. Furthermore, the
      strength of motor response to air infusion when compared to water swallows was
      diminished in achalasia patients but not in healthy subjects and NOD.
      CONCLUSIONS: Motor response to rapid air infusion was variably impaired in
      achalasia. The role of this alteration in the long-term outcome deserves
      evaluation.

PMID- 24918013
TI  - Risk factors for the development of oesophageal adenocarcinoma in Barrett's
      oesophagus: a UK primary care retrospective nested case-control study.
AB  - BACKGROUND: Oesophageal adenocarcinoma (OAC) incidence is rising rapidly and
      prognosis remains poor. Endoscopic surveillance of Barrett's oesophagus (BO)
      remains controversial. OBJECTIVE: A nested case-control study was undertaken to
      evaluate risk factors for progression of BO to OAC, potentially guiding
      surveillance efforts. METHODS: The Health Improvement Network database includes
      general practitioner consultations from 5 million UK subjects. BO subjects with 1
      year minimum of follow up were followed until development of OAC or end of time
      on database. Demographic variables (age, gender, smoking, body mass index) and
      data on medication considered negatively (aspirin/nonsteroidal anti-inflammatory
      drugs/proton pump inhibitors) or positively associated (lower oesophageal
      sphincter-relaxing and asthma drugs) with OAC development were studied. Cox
      regression analysis-derived hazard ratios with 95% confidence intervals estimated
      the relative risk for OAC progression. RESULTS: A total of 3749 BO subjects were
      studied: 55 developed OAC during 17,743 patient years of follow up, a progression
      rate of 0.3% per annum. There was 96.7% of the cohort who took proton-pump
      inhibitors, with no association observed. Increasing age (1.03, 95% CI 1.01-1.05,
      p = 0.005), male gender (3.06, 95% CI 1.50-6.24, p = 0.002), and having ever
      smoked (2.36, 95% CI 1.13-4.93, p = 0.023) were associated with progression to
      OAC, (although smoking lost association on multivariate analysis). Increasing
      number of drugs used for asthma (2.91, 95% CI 1.10-7.68, p= 0.0314) was also
      associated. CONCLUSION: In this nested case-control study of BO, male gender,
      increasing age, and increasing use of asthma drugs were associated with
      progression to OAC.

PMID- 24918014
TI  - Clinical significance of hepatitis B virion and SVP productivity: relationships
      between intrahepatic and serum markers in chronic hepatitis B patients.
AB  - BACKGROUND: Clinical use of hepatitis B viral (HBV) quantitative seromarker?s
      remains questionable since it is not precisely known whether they represent
      intrahepatic viral replication. Covalently closed circular DNA (cccDNA), relaxed
      circular DNA (rcDNA), and pregenomic RNA (pgRNA) are more likely to represent
      active HBV replication and their measurement can be used to derive virion
      productivity (VP; rcDNA/cccDNA), subviral particle (SVP) productivity
      (quantitative HBsAg/cccDNA), and replicative activity (RA; pgRNA/cccDNA). These
      can be used to compare relative HBV replication between HBeAg-negative and 
      positive patients. OBJECTIVE: To study the clinical significance of intrahepatic
      HBV replication phenomenon between HBeAg-negative and -positive patients and its
      correlation with quantitative HBV seromarkers. METHOD: This was a prospective
      study between January 2010 and December 2011. Study subjects were naive chronic
      hepatitis B patients from Cipto Mangunkusumo and Medistra Hospitals. All patient
      samples underwent liver biochemistry and HBV seromarkers testing (HBeAg,
      quantitative HBsAg and HBV DNA levels), and patients underwent liver biopsy.
      Stored liver specimens were analysed for intrahepatic rcDNA, cccDNA, and pgRNA
      with quantification performed by real-time PCR. Comparison of HBV markers between
      HBsAg-positive and -negative patients was carried out using the Mann-Whitney U
      test. Pearson's correlation test was performed among HBV intrahepatic and
      seromarkers using their log-transformed values. RESULTS: A total of 104 patients
      were enrolled in this study; 54 (51.9%) were male. Patients' mean age was 41.9 +/
      11.63 years (range 19-70 years). Sixty-one patients (58.7%) were HBeAg-negative.
      All HBV markers were significantly higher in HBeAg-positive than HBeAg-negative
      patients, except for SVP productivity and RA. Serum HBV DNA was strongly
      correlated with intrahepatic total HBV DNA (r = 0.771), cccDNA (r = 0.774), and
      rcDNA (r = 0.780) while serum quantitative HBsAg showed only moderate correlation
      with intrahepatic total DNA (r = 0.671), cccDNA (r = 0.632), rcDNA (r = 0.675),
      and SVP productivity (r = 0.557). CONCLUSIONS: Serum HBV DNA concentration and
      quantitative HBsAg might not accurately predict intrahepatic viral activity.
      Virion and SVP production do not occur in parallel with replicative activity.

PMID- 24918015
TI  - Long-term outcome of cyclosporin rescue therapy in acute, steroid-refractory
      severe ulcerative colitis.
AB  - BACKGROUND: Although cyclosporin is effective in severe ulcerative colitis (UC),
      long-term colectomy rate varies between 60 and 88% among patients in whom
      cyclosporin initially induced remission. The aim of our study was to evaluate the
      long-term outcome and the optimal duration of cyclosporin therapy in acute,
      severe UC. METHODS: A total of 73 patients underwent i.v. cyclosporin therapy for
      a steroid refractory flare up of UC between 1998 and 2009. All patients were
      treated with 1 mg/kg i.v. methylprednisolone for 3-7 days before the
      administration of cyclosporin. Patients received i.v. cyclosporin of 4-5 mg/kg
      for 5 days following oral treatment. RESULTS: The mean follow up after the
      initiation of cyclosporin was 4.2 years. There were 20 patients who underwent
      early colectomy. Cyclosporin had to be discontinued due to side effects in 22
      patients. Cyclosporin failed and late colectomy was performed in 14 of the 53
      responders. Duration of cyclosporin treatment was significantly longer in those
      who avoided colectomy. The probability of avoiding colectomy proved to be 66% in
      case of 1-year treatment period with cyclosporin. The longer treatment period
      resulted in longer colectomy-free disease course. CONCLUSIONS: Cyclosporin is
      effective in acute, severe UC during long-term follow up. Our data suggest that
      the longer cyclosporin is used, the more it is possible to avoid colectomy in the
      future.

PMID- 24918016
TI  - Gelatin tannate ameliorates acute colitis in mice by reinforcing mucus layer and
      modulating gut microbiota composition: Emerging role for 'gut barrier protectors'
      in IBD?
AB  - BACKGROUND: Gelatin tannate, a gelatin powder containing tannic acids, is
      commonly employed as an intestinal astringent. Neither information nor animal
      model exist to confirm its efficacy or unravel mechanisms of action. OBJECTIVE:
      To evaluate the action of gelatin tannate in murine dextran sodium sulphate (DSS)
      induced acute colitis. METHODS: Mice were exposed to DSS and received gelatin
      tannate by gavage. At sacrifice, colon histological degree of inflammation was
      assessed. Stool samples were cultured for microbiological analysis. Colon samples
      were analysed by two-photon confocal microscopy and atomic force microscopy.
      Elisa was performed on murine serum to assess lipopolysaccharide and
      peptidoglycan levels. RESULTS: Gelatin tannate treatment reduced disease
      activity, bodyweight loss, and preserved colonic length. It produced a decrease
      in the amount of enterobacteria and enterococci. At confocal microscopy,
      intestinal samples from healthy and treated mice displayed similar structure in
      mucus layer thickness and composition; samples from placebo group had no mucus
      layer or a thinner stratus. Atomic force microscopy confirmed these findings.
      Treated mice showed lower blood LPS levels vs. control. CONCLUSIONS: Gelatin
      tannate decreased the severity of colitis. Acting as a gut barrier enhancer, it
      re-establishes gut homeostasis by recovering intestinal permeability and mucus
      layer integrity in gut mucosa and by modulating microbiota composition.

PMID- 24918017
TI  - Postpolypectomy haemorrhage following removal of large polyps using mechanical
      haemostasis or epinephrine: a meta-analysis.
AB  - BACKGROUND AND AIM: Postpolypectomy haemorrhage (PPH) is a known adverse event
      that can occur following polypectomy, occurring in 0.3-6.1% of cases. Previous
      meta-analysis has included small polyps, which are less likely to bleed, and less
      amenable to some methods of mechanical haemostasis. No comprehensive cost-benefit
      analysis of this topic is available. The aim of this study was to perform a meta
      analysis of randomized trials and a cost-benefit analysis of prophylactic
      haemostasis in PPH. METHODS: A total of 3092 abstracts from prospective trials
      conducted in human colonoscopic polypectomy were screened. Outpatients undergoing
      polypectomy in seven suitable studies (1426 episodes), without polyposis
      syndromes or bleeding diathesis, were identified. The interventions of
      prophylactic haemostatic measures (clips, loops, and/or adrenaline injection) to
      prevent PPH were assessed. The main outcome measurements were PPH measured by
      haematochezia or drop in haematocrit >10% or haemoglobin >1 g/dl. Risk ratio and
      number needed to treat (NNT) were generated using meta-analysis. RESULTS:
      Comparing any prophylactic haemostasis to none, the pooled risk ratio for PPH was
      0.35 (0.21-0.57; p < 0.0001), NNT was 13.6, and cost to prevent one PPH was
      USD652. Using adrenaline alone vs. no prophylactic haemostasis revealed a pooled
      risk ratio of 0.37 (0.20-0.66; p = 0.001), NNT 14.0, cost to prevent one PPH
      USD382. Any prophylactic mechanical haemostasis compared to adrenaline produced a
      RR for PPH of 0.28 (0.14-0.57; p < 0.0001), NNT 12.3, and cost to prevent one PPH
      USD1368. CONCLUSIONS: Adrenaline injection or mechanical haemostasis reduces the
      risk of PPH. Routine prophylactic measures to reduce PPH for polyps larger than
      10 mm are potentially cost effective, although more thorough cost-benefit
      modelling is required.

PMID- 24918019
TI  - UEG Week Vienna 2014 cutting edge symposium: Today's Science, Tomorrow's Medicine
      session features the immune system - a driving force in digestive health and
      disease.

PMID- 24918018
TI  - Symptomatic fructose malabsorption in irritable bowel syndrome: A prospective
      study.
AB  - INTRODUCTION: Fructose can trigger or worsen symptoms in irritable bowel syndrome
      (IBS) patients. The aim of this study was to determine the prevalence of
      symptomatic fructose malabsorption in IBS patients and to test whether the
      patient's characteristics can help to detect a fructose malabsorption. MATERIALS
      AND METHODS: Ninety Rome III IBS patients (predominant diarrhoea (IBS-D): 31%,
      predominant constipation (IBS-C): 18%, mixed type (IBS-M): 51%) were included
      prospectively. After exclusion of a small intestinal bacterial overgrowth by a
      glucose breath test, fructose malabsorption was assessed by a five-hour breath
      test, with symptom monitoring, after a 25 g load of fructose. An increase of more
      than 20 ppm of hydrogen (H2) or methane (CH4) levels in the exhaled air led to
      the diagnosis of malabsorption. RESULTS: Fructose test was abnormal in 20/90
      patients among whom only 35% were intolerant, with a simultaneous rise of H2/CH4
      levels and the onset of abdominal discomfort or diarrhoea. IBS characteristics
      were not predictive even if young (p = 0.031) and male IBS patients (p = 0.029)
      were at higher risk of malabsorption. At variance, 18 additional patients
      experienced intestinal symptoms during the test despite normal fructose
      absorption. DISCUSSION: After a 25 g fructose load, symptomatic fructose
      malabsorption and intolerance without malabsorption were detected in 22% and 28%
      of IBS patients respectively.

PMID- 24918020
TI  - UEG Training Support - a good option to finance your high quality postgraduate
      teaching!

PMID- 24918021
TI  - Representation of national matters in UEG.

PMID- 24918022
TI  - The Medicaid medically improved group: losing disability status and growing
      earnings.
AB  - OBJECTIVES: Under the Ticket to Work and Work Incentives Improvement Act (PL 106
      170), states may extend Medicaid Buy-In coverage to a medically improved group.
      Improved group coverage allows adults with disabilities to retain Medicaid
      coverage even once they lose disability status due to medical improvement, as
      long as they retain the original medical impairment. The goal of this paper is to
      describe who participated, the patterns of their participation, and employment
      outcomes. METHODS: The study population consists of all individuals (n = 315) who
      participated in medically improved group coverage 2002-2009 in the seven states
      with coverage by 2009 (Arizona, Connecticut, Kansas, New York, North Carolina,
      Pennsylvania, and West Virginia). Linked data from state Medicaid Buy-In finder
      files and Social Security Administration Ticket Research and Master Earnings
      Files were used to describe improved group participants and their patterns of
      enrollment. RESULTS: Although enrollment has been limited, with 255 participants
      in 2009, it has doubled annually on average with little churning and drop-out.
      Participants' earnings grew nearly 200 dollars per month after two years, likely
      reflecting increased work hours and/or higher pay rates. CONCLUSIONS: Improved
      group participants represent an unusually successful group of individuals with
      disabilities, many of whom have recently moved off Social Security cash benefit
      rolls or who were diverted from them. Specifics of insurance eligibility and
      coverage for improved group participants are uncertain under the Affordable Care
      Act. The challenge remains to provide a pathway for adults with disabilities to
      increase work and assets without loss of adequate health insurance.

PMID- 24918023
TI  - Impacts of generic competition and benefit management practices on spending for
      prescription drugs: evidence from Medicare's Part D benefit.
AB  - OBJECTIVE: This study estimates the effects of generic competition, increased
      cost-sharing, and benefit practices on utilization and spending for prescription
      drugs. DATA AND METHODS: We examined changes in Medicare price and utilization
      from 2007 to 2009 of all drugs in 28 therapeutic classes. The classes accounted
      for 80% of Medicare Part D spending in 2009 and included the 6 protected classes
      and 6 classes with practically no generic competition. All variables were
      constructed to measure each drug relative to its class at a specific plan
      sponsor. RESULTS: We estimated that the shift toward generic utilization had cut
      in half the rate of increase in the price of a prescription during 2007-2009.
      Specifically, the results showed that (1) rapid generic penetration had
      significantly held down costs per prescription, (2) copayment and other benefit
      practices shifted utilization to generics and favored brands, and (3) price
      increases were generally greater in less competitive classes of drugs.
      CONCLUSION: In many ways, Part D was implemented at a fortuitous time; since
      2006, there have been relatively few new blockbuster drugs introduced, and many
      existing high-volume drugs used by beneficiaries were in therapeutic classes with
      multiple brands and generic alternatives. Under these conditions, our paper
      showed that plan sponsors have been able to contain costs by encouraging use of
      generics or drugs offering greater value within therapeutic classes. It is less
      clear what will happen to future Part D costs if a number of new and effective
      drugs for beneficiaries enter the market with no real competitors.

PMID- 24918025
TI  - Hemichorea Associated with CASPR2 Antibody.
AB  - This letter was written in response to: Ramdhani RA, Frucht SJ. Isolated chorea
      associated with LGI1 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi:
      10.7916/D8MG7MFC. 

PMID- 24918024
TI  - Neuroimaging studies of essential tremor: how well do these studies
      support/refute the neurodegenerative hypothesis?
AB  - BACKGROUND: Tissue-based research has recently led to a new patho-mechanistic
      model of essential tremor (ET)-the cerebellar degenerative model. We are not
      aware of a study that has reviewed the current neuroimaging evidence, focusing on
      whether the studies support or refute the neurodegenerative hypothesis of ET.
      This was our aim. METHODS: References for this review were identified by searches
      of PubMed (1966 to February 2014). RESULTS: Several neuroimaging methods have
      been used to study ET, most of them based on magnetic resonance imaging (MRI).
      The methods most specific to address the question of neurodegeneration are MRI
      based volumetry, magnetic resonance spectroscopy, and diffusion-weighted imaging.
      Studies using each of these methods provide support for the presence of
      cerebellar degeneration in ET, finding reduced cerebellar brain volumes,
      consistent decreases in cerebellar N-acetylaspartate, and increased mean
      diffusivity. Other neuroimaging techniques, such as functional MRI and positron
      emission tomography (PET) are less specific, but still sensitive to potential
      neurodegeneration. These techniques are used for measuring a variety of brain
      functions and their impairment. Studies using these modalities also largely
      support cerebellar neuronal impairment. In particular, changes in (11)C
      flumazenil binding in PET studies and changes in iron deposition in an MRI study
      provide evidence along these lines. The composite data point to neuronal
      impairment and likely neuronal degeneration in ET. DISCUSSION: Recent years have
      seen a marked increase in the number of imaging studies of ET. As a whole, the
      combined data provide support for the presence of cerebellar neuronal
      degeneration in this disease.

PMID- 24918026
TI  - Reply to: Hemichorea Associated with CASPR2 Antibody.
AB  - This letter was written in reply to this letter to the editor: Vynogradova I,
      Savitski V, Heckmann JG. Hemichorea associated with CASPR2 antibody. Tremor Other
      Hyperkinet Mov. 2014; 4. doi: 10.7916/D8VM49C5. The above letter to the editor
      was written in response to this article: Ramdhani RA, Frucht SJ. Isolated Chorea
      Associated with LGI1 Antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi:
      10.7916/D8MG7MFC. 

PMID- 24918027
TI  - Quantitative trait loci for energy balance traits in an advanced intercross line
      derived from mice divergently selected for heat loss.
AB  - Obesity in human populations, currently a serious health concern, is considered
      to be the consequence of an energy imbalance in which more energy in calories is
      consumed than is expended. We used interval mapping techniques to investigate the
      genetic basis of a number of energy balance traits in an F11 advanced intercross
      population of mice created from an original intercross of lines selected for
      increased and decreased heat loss. We uncovered a total of 137 quantitative trait
      loci (QTLs) for these traits at 41 unique sites on 18 of the 20 chromosomes in
      the mouse genome, with X-linked QTLs being most prevalent. Two QTLs were found
      for the selection target of heat loss, one on distal chromosome 1 and another on
      proximal chromosome 2. The number of QTLs affecting the various traits generally
      was consistent with previous estimates of heritabilities in the same population,
      with the most found for two bone mineral traits and the least for feed intake and
      several body composition traits. QTLs were generally additive in their effects,
      and some, especially those affecting the body weight traits, were sex-specific.
      Pleiotropy was extensive within trait groups (body weights, adiposity and organ
      weight traits, bone traits) and especially between body composition traits
      adjusted and not adjusted for body weight at sacrifice. Nine QTLs were found for
      one or more of the adiposity traits, five of which appeared to be unique. The
      confidence intervals among all QTLs averaged 13.3 Mb, much smaller than usually
      observed in an F2 cross, and in some cases this allowed us to make reasonable
      inferences about candidate genes underlying these QTLs. This study combined QTL
      mapping with genetic parameter analysis in a large segregating population, and
      has advanced our understanding of the genetic architecture of complex traits
      related to obesity. 

PMID- 24918028
TI  - TGF-beta1 of no avail as prognostic marker in lyme disease.
AB  - Background. Within the present in vivo study using the wild type mouse strains
      C3H/HeN and FVB/N it was intended to (1) measure TGF-beta1 expression in the
      course of lyme disease, (2) examine the potential correlation of TGF-beta1
      expression with the clinical outcome of a Borrelia infection (with a focus on
      lyme arthritis), (3) develop a diagnostic tool based on the endogenous factor TGF
      beta1 to predict the progressivity of lyme disease. Findings. In the course of
      lyme disease there was an increase in the serum content of active TGF-beta1,
      which became significant 56 days post infection (p < 0.001). The serum
      concentration of total TGF-beta1 in the course of infection initially decreased
      then rebounded and subsequently dropped again. Despite considerable individual
      variations in active TGF-beta1 serum concentrations there were no identifiable
      dissimilarities in the clinical appearance of the mice. Likewise, no correlation
      could be seen between the serum content of active TGF-beta1 and the severity of
      lyme arthritis of tibiotarsal joints of infected mice. Conclusions. The present
      study clearly shows that TGF-beta1 is of no avail as prognostic marker in lyme
      disease. Hence, the search for an endogenous predictive factor, which can be
      determined in an easy and reliable manner, remains open. 

PMID- 24918029
TI  - Diagnosing the dangerous demography of manta rays using life history theory.
AB  - Background. The directed harvest and global trade in the gill plates of mantas,
      and devil rays, has led to increased fishing pressure and steep population
      declines in some locations. The slow life history, particularly of the manta
      rays, is cited as a key reason why such species have little capacity to withstand
      directed fisheries. Here, we place their life history and demography within the
      context of other sharks and rays. Methods. Despite the limited availability of
      data, we use life history theory and comparative analysis to estimate the
      intrinsic risk of extinction (as indexed by the maximum intrinsic rate of
      population increase r max) for a typical generic manta ray using a variant of the
      classic Euler-Lotka demographic model. This model requires only three traits to
      calculate the maximum intrinsic population growth rate r max: von Bertalanffy
      growth rate, annual pup production and age at maturity. To account for the
      uncertainty in life history parameters, we created plausible parameter ranges and
      propagate these uncertainties through the model to calculate a distribution of
      the plausible range of r max values. Results. The maximum population growth rate
      r max of manta ray is most sensitive to the length of the reproductive cycle, and
      the median r max of 0.116 year(-1) 95th percentile [0.089-0.139] is one of the
      lowest known of the 106 sharks and rays for which we have comparable demographic
      information. Discussion. In common with other unprotected, unmanaged, high-value
      large-bodied sharks and rays the combination of very low population growth rates
      of manta rays, combined with the high value of their gill rakers and the
      international nature of trade, is highly likely to lead to rapid depletion and
      potential local extinction unless a rapid conservation management response occurs
      worldwide. Furthermore, we show that it is possible to derive important insights
      into the demography extinction risk of data-poor species using well-established
      life history theory. 

PMID- 24918030
TI  - Aerosol delivery of synthetic lung surfactant.
AB  - Background. Nasal continuous positive airway pressure (nCPAP) is a widely
      accepted technique of non-invasive respiratory support in premature infants with
      respiratory distress syndrome due to lack of lung surfactant. If this approach
      fails, the next step is often intubation, mechanical ventilation (MV) and
      intratracheal instillation of clinical lung surfactant. Objective. To investigate
      whether aerosol delivery of advanced synthetic lung surfactant, consisting of
      peptide mimics of surfactant proteins B and C (SP-B and SP-C) and synthetic
      lipids, during nCPAP improves lung function in surfactant-deficient rabbits.
      Methods. Experimental synthetic lung surfactants were produced by formulating 3%
      Super Mini-B peptide (SMB surfactant), a highly surface active SP-B mimic, and a
      combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC
      surfactant), with a synthetic lipid mixture. After testing aerosol generation
      using a vibrating membrane nebulizer and aerosol conditioning (particle size,
      surfactant composition and surface activity), we investigated the effects of
      aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation
      and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported
      with either nCPAP or MV. Results. Particle size distribution of the surfactant
      aerosols was within the 1-3 um distribution range and surfactant activity was not
      affected by aerosolization. At a dose equivalent to clinical surfactant therapy
      in premature infants (100 mg/kg), aerosol delivery of both synthetic surfactant
      preparations led to a quick and clinically relevant improvement in oxygenation
      and lung compliance in the rabbits. Lung function recovered to a greater extent
      in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB
      surfactant in improving lung function and was associated with higher phospholipid
      values in bronchoalveolar lavage fluid; these findings were irrespective of the
      type of ventilatory support (nCPAP or MV) used. Conclusions. Aerosol delivery of
      synthetic lung surfactant with a combination of highly active second generation
      SP-B and SP-C mimics was effective as a therapeutic approach towards relieving
      surfactant deficiency in spontaneously breathing rabbits supported with nCPAP. To
      obtain similar results with nCPAP as with intratracheal instillation, higher
      dosage of synthetic surfactant and reduction of its retention by the delivery
      circuit will be needed to increase the lung dose. 

PMID- 24918031
TI  - New information on the anatomy of the Chinese Early Cretaceous Bohaiornithidae
      (Aves: Enantiornithes) from a subadult specimen of Zhouornis hani.
AB  - Enantiornithines are the most diverse avian clade in the Cretaceous. However,
      morphological specializations indicative of specific ecological roles are not
      well known for this clade. Here we report on an exquisitely well-preserved
      specimen from the Lower Cretaceous Jehol Group of northeastern China, which pedal
      morphology is suggestive of a unique ecological specialization within
      Enantiornithes. The morphology of the new specimen is largely indistinguishable
      from that of the holotype of the bohaiornithid enantiornithine Zhouornis hani,
      albeit the latter is somewhat larger. The new specimen provides important and
      previously unknown details of the skull of Zhouornis hani, which add to the
      limited knowledge about the cranial anatomy and evolution of enantiornithines.
      The information offered by the new specimen also augments our understanding of
      the postcranial morphology of bohaiornithid enantiornithines, a clade that has
      been only recently recognized. With the description of this specimen, Zhouornis
      hani becomes one of the most anatomically complete known enantiornithine species,
      which will facilitate future morphological studies. 

PMID- 24918032
TI  - Prey aggregation is an effective olfactory predator avoidance strategy.
AB  - Predator-prey interactions have a major effect on species abundance and
      diversity, and aggregation is a well-known anti-predator behaviour. For immobile
      prey, the effectiveness of aggregation depends on two conditions: (a) the
      inability of the predator to consume all prey in a group and (b) detection of a
      single large group not being proportionally easier than that of several small
      groups. How prey aggregation influences predation rates when visual cues are
      restricted, such as in turbid water, has not been thoroughly investigated. We
      carried out foraging (predation) experiments using a fish predator and (dead)
      chironomid larvae as prey in both laboratory and field settings. In the
      laboratory, a reduction in visual cue availability (in turbid water) led to a
      delay in the location of aggregated prey compared to when visual cues were
      available. Aggregated prey suffered high mortality once discovered, leading to
      better survival of dispersed prey in the longer term. We attribute this to the
      inability of the dead prey to take evasive action. In the field (where prey were
      placed in feeding stations that allowed transmission of olfactory but not visual
      cues), aggregated (large groups) and semi-dispersed prey survived for longer than
      dispersed prey-including long term survival. Together, our results indicate that
      similar to systems where predators hunt using vision, aggregation is an effective
      anti-predator behaviour for prey avoiding olfactory predators. 

PMID- 24918033
TI  - Contrasting effects of ocean acidification on tropical fleshy and calcareous
      algae.
AB  - Despite the heightened awareness of ocean acidification (OA) effects on marine
      organisms, few studies empirically juxtapose biological responses to CO2
      manipulations across functionally distinct primary producers, particularly
      benthic algae. Algal responses to OA may vary because increasing CO2 has the
      potential to fertilize photosynthesis but impair biomineralization. Using a
      series of repeated experiments on Palmyra Atoll, simulated OA effects were tested
      across a suite of ecologically important coral reef algae, including five fleshy
      and six calcareous species. Growth, calcification and photophysiology were
      measured for each species independently and metrics were combined from each
      experiment using a meta-analysis to examine overall trends across functional
      groups categorized as fleshy, upright calcareous, and crustose coralline algae
      (CCA). The magnitude of the effect of OA on algal growth response varied by
      species, but the direction was consistent within functional groups. Exposure to
      OA conditions generally enhanced growth in fleshy macroalgae, reduced net
      calcification in upright calcareous algae, and caused net dissolution in CCA.
      Additionally, three of the five fleshy seaweeds tested became reproductive upon
      exposure to OA conditions. There was no consistent effect of OA on algal
      photophysiology. Our study provides experimental evidence to support the
      hypothesis that OA will reduce the ability of calcareous algae to biomineralize.
      Further, we show that CO2 enrichment either will stimulate population or somatic
      growth in some species of fleshy macroalgae. Thus, our results suggest that
      projected OA conditions may favor non-calcifying algae and influence the relative
      dominance of fleshy macroalgae on reefs, perpetuating or exacerbating existing
      shifts in reef community structure. 

PMID- 24918034
TI  - Increasing the precision of orthology-based complex prediction through network
      alignment.
AB  - Macromolecular assemblies play an important role in almost all cellular
      processes. However, despite several large-scale studies, our current knowledge
      about protein complexes is still quite limited, thus advocating the use of in
      silico predictions to gather information on complex composition in model
      organisms. Since protein-protein interactions present certain constraints on the
      functional divergence of macromolecular assemblies during evolution, it is
      possible to predict complexes based on orthology data. Here, we show that
      incorporating interaction information through network alignment significantly
      increases the precision of orthology-based complex prediction. Moreover, we
      performed a large-scale in silico screen for protein complexes in human, yeast
      and fly, through the alignment of hundreds of known complexes to whole organism
      interactomes. Systematic comparison of the resulting network alignments to all
      complexes currently known in those species revealed many conserved complexes, as
      well as several novel complex components. In addition to validating our
      predictions using orthogonal data, we were able to assign specific functional
      roles to the predicted complexes. In several cases, the incorporation of
      interaction data through network alignment allowed to distinguish real complex
      components from other orthologous proteins. Our analyses indicate that current
      knowledge of yeast protein complexes exceeds that in other organisms and that
      predicting complexes in fly based on human and yeast data is complementary rather
      than redundant. Lastly, assessing the conservation of protein complexes of the
      human pathogen Mycoplasma pneumoniae, we discovered that its complexes repertoire
      is different from that of eukaryotes, suggesting new points of therapeutic
      intervention, whereas targeting the pathogen's Restriction enzyme complex might
      lead to adverse effects due to its similarity to ATP-dependent metalloproteases
      in the human host. 

PMID- 24918035
TI  - Strain- and plasmid-level deconvolution of a synthetic metagenome by sequencing
      proximity ligation products.
AB  - Metagenomics is a valuable tool for the study of microbial communities but has
      been limited by the difficulty of "binning" the resulting sequences into groups
      corresponding to the individual species and strains that constitute the
      community. Moreover, there are presently no methods to track the flow of mobile
      DNA elements such as plasmids through communities or to determine which of these
      are co-localized within the same cell. We address these limitations by applying
      Hi-C, a technology originally designed for the study of three-dimensional genome
      structure in eukaryotes, to measure the cellular co-localization of DNA
      sequences. We leveraged Hi-C data generated from a simple synthetic metagenome
      sample to accurately cluster metagenome assembly contigs into groups that contain
      nearly complete genomes of each species. The Hi-C data also reliably associated
      plasmids with the chromosomes of their host and with each other. We further
      demonstrated that Hi-C data provides a long-range signal of strain-specific
      genotypes, indicating such data may be useful for high-resolution genotyping of
      microbial populations. Our work demonstrates that Hi-C sequencing data provide
      valuable information for metagenome analyses that are not currently obtainable by
      other methods. This metagenomic Hi-C method could facilitate future studies of
      the fine-scale population structure of microbes, as well as studies of how
      antibiotic resistance plasmids (or other genetic elements) mobilize in microbial
      communities. The method is not limited to microbiology; the genetic architecture
      of other heterogeneous populations of cells could also be studied with this
      technique. 

PMID- 24918036
TI  - Biogeographic patterns in the cartilaginous fauna (Pisces: Elasmobranchii and
      Holocephali) in the southeast Pacific Ocean.
AB  - The abundance and species richness of the cartilaginous fish community of the
      continental shelf and slope off central Chile is described, based on fishery
      independent trawl tows made in 2006 and 2007. A total of 194,705 specimens
      comprising 20 species (9 sharks, 10 skates, 1 chimaera) were caught at depths of
      100-500 m along a 1,000 km transect between 29.5 degrees S and 39 degrees S.
      Sample site locations were grouped to represent eight geographical zones within
      this latitudinal range. Species richness fluctuated from 1 to 6 species per zone.
      There was no significant latitudinal trend for sharks, but skates showed an
      increased species richness with latitude. Standardised catch per unit effort
      (CPUE) increased with increasing depth for sharks, but not for skates, but the
      observed trend for increasing CPUE with latitude was not significant for either
      sharks or skates. A change in community composition occurred along the depth
      gradient with the skates, Psammobatis rudis, Zearaja chilensis and Dipturus
      trachyderma dominating communities between 100 and 300 m, but small-sized, deep
      water dogfishes, such as Centroscyllium spp. dominated the catch between 300 and
      500 m. Cluster and ordination analysis identified one widespread assemblage,
      grouping 58% of sites, and three shallow-water assemblages. Assemblages with low
      diversity (coldspots) coincided with highly productive fishing grounds for
      demersal crustaceans and bony fishes. The community distribution suggested that
      the differences between assemblages may be due to compensatory changes in
      mesopredator species abundance, as a consequence of continuous and unselective
      species removal. Distribution patterns and the quantitative assessment of sharks,
      skates and chimaeras presented here complement extant biogeographic knowledge and
      further the understanding of deep-water ecosystem dynamics in relation to fishing
      activity in the south-east Pacific Ocean. 

PMID- 24918037
TI  - Molecular pathway alterations in CD4 T-cells of nonobese diabetic (NOD) mice in
      the preinsulitis phase of autoimmune diabetes.
AB  - Type 1 diabetes (T1D) is a multigenic disease caused by T-cell mediated
      destruction of the insulin producing pancreatic islet beta-cells. The earliest
      sign of islet autoimmunity in NOD mice, islet leukocytic infiltration or
      insulitis, is obvious at around 5 weeks of age. The molecular alterations that
      occur in T cells prior to insulitis and that may contribute to T1D development
      are poorly understood. Since CD4 T-cells are essential to T1D development, we
      tested the hypothesis that multiple genes/molecular pathways are altered in these
      cells prior to insulitis. We performed a genome-wide transcriptome and pathway
      analysis of whole, untreated CD4 T-cells from 2, 3, and 4 week-old NOD mice in
      comparison to two control strains (NOR and C57BL/6). We identified many
      differentially expressed genes in the NOD mice at each time point. Many of these
      genes (herein referred to as NOD altered genes) lie within known diabetes
      susceptibility (insulin-dependent diabetes, Idd) regions, e.g. two diabetes
      resistant loci, Idd27 (tripartite motif-containing family genes) and Idd13
      (several genes), and the CD4 T-cell diabetogenic activity locus, Idd9/11 (2
      genes, KH domain containing, RNA binding, signal transduction associated 1 and
      protein tyrosine phosphatase 4a2). The biological processes associated with these
      altered genes included, apoptosis/cell proliferation and metabolic pathways
      (predominant at 2 weeks); inflammation and cell signaling/activation (predominant
      at 3 weeks); and innate and adaptive immune responses (predominant at 4 weeks).
      Pathway analysis identified several factors that may regulate these
      abnormalities: eight, common to all 3 ages (interferon regulatory factor 1,
      hepatic nuclear factor 4, alpha, transformation related protein 53, BCL2-like 1
      (lies within Idd13), interferon gamma, interleukin 4, interleukin 15, and
      prostaglandin E2); and two each, common to 2 and 4 weeks (androgen receptor and
      interleukin 6); and to 3 and 4 weeks (interferon alpha and interferon regulatory
      factor 7). Others were unique to the various ages, e.g. myelocytomatosis
      oncogene, jun oncogene, and amyloid beta (A4) to 2 weeks; tumor necrosis factor,
      transforming growth factor, beta 1, NF?B, ERK, and p38MAPK to 3 weeks; and
      interleukin 12 and signal transducer and activator of transcription 4 to 4 weeks.
      Thus, our study demonstrated that expression of many genes that lie within
      several Idds (e.g. Idd27, Idd13 and Idd9/11) was altered in CD4 T-cells in the
      early induction phase of autoimmune diabetes and identified their associated
      molecular pathways. These data offer the opportunity to test hypotheses on the
      roles played by the altered genes/molecular pathways, to understand better the
      mechanisms of CD4 T-cell diabetogenesis, and to develop new therapeutic
      strategies for T1D. 

PMID- 24918038
TI  - Lentiviral vector transduction of spermatozoa as a tool for the study of early
      development.
AB  - Spermatozoa and lentiviruses are two of nature's most efficient gene delivery
      vehicles. Both can be genetically modified and used independently for the
      generation of transgenic animals or gene transfer/therapy of inherited disorders.
      Here we show that mature spermatozoa can be directly transduced with various
      pseudotyped lentiviral vectors and used in in vitro fertilisation studies.
      Lentiviral vectors encoding Green Fluorescent Protein (GFP) were shown to be
      efficiently processed and expressed in sperm. When these transduced sperm were
      used in in vitro fertilisation studies, GFP expression was observed in arising
      blastocysts. This simple technique of directly transducing spermatozoa has
      potential to be a powerful tool for the study of early and pre-implantation
      development and could be used as a technique in transgenic development and
      vertical viral transmission studies. 

PMID- 24918039
TI  - Tracing the movement of adiponectin in a parabiosis model of wild-type and
      adiponectin-knockout mice.
AB  - Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic,
      anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is
      associated in obese individuals with insulin resistance and atherosclerosis.
      However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here,
      we investigated adiponectin movement using hetero parabiosis model of wild type
      (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice
      (WT-WT) or KO mice (WT-KO) and adiponectin levels were measured serially up to 63
      days after surgery. In the WT-KO parabiosis model, circulating adiponectin levels
      of the WT partners decreased rapidly, on the other hand, those of KO partners
      increased, and then these reached comparable levels each other at day 7.
      Circulating adiponectin levels decreased further to the detection limit of assay,
      and remained low up to day 63. However, adiponectin protein was detected in the
      adipose tissues of not only the WT partner but also WT-KO mice. In the diet
      induced obesity model, high adiponectin protein levels were detected in adipose
      stromal vascular fraction of diet-induced obese KO partner, without changes in
      its binding proteins. The use of parabiosis experiments shed light on movement of
      native adiponectin among different tissues such as the state of
      hypoadiponectinemia in obesity. 

PMID- 24918040
TI  - Structure of the C-terminal domain of AspA (antigen I/II-family) protein from
      Streptococcus pyogenes.
AB  - The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in
      humans, including moderate infections such as pharyngitis (strep throat) as well
      as life threatening conditions such as necrotizing fasciitis and puerperal fever.
      The antigen I/II family proteins are cell wall anchored adhesin proteins found on
      the surfaces of most oral streptococci and are involved in host colonization and
      biofilm formation. In the present study we have determined the crystal structure
      of the C2-3-domain of the antigen I/II type protein AspA from S. pyogenes M type
      28. The structure was solved to 1.8 A resolution and shows that the C2-3-domain
      is comprised of two structurally similar DEv-IgG motifs, designated C2 and C3,
      both containing a stabilizing covalent isopeptide bond. Furthermore a metal
      binding site is identified, containing a bound calcium ion. Despite relatively
      low sequence identity, interestingly, the overall structure shares high
      similarity to the C2-3-domains of antigen I/II proteins from Streptococcus
      gordonii and Streptococcus mutans, although certain parts of the structure
      exhibit distinct features. In summary this work constitutes the first step in the
      full structure determination of the AspA protein from S. pyogenes. 

PMID- 24918041
TI  - Functional characterization of diverse ring-hydroxylating oxygenases and
      induction of complex aromatic catabolic gene clusters in Sphingobium sp. PNB.
AB  - Sphingobium sp. PNB, like other sphingomonads, has multiple ring-hydroxylating
      oxygenase (RHO) genes. Three different fosmid clones have been sequenced to
      identify the putative genes responsible for the degradation of various aromatics
      in this bacterial strain. Comparison of the map of the catabolic genes with that
      of different sphingomonads revealed a similar arrangement of gene clusters that
      harbors seven sets of RHO terminal components and a sole set of electron
      transport (ET) proteins. The presence of distinctly conserved amino acid residues
      in ferredoxin and in silico molecular docking analyses of ferredoxin with the
      well characterized terminal oxygenase components indicated the structural
      uniqueness of the ET component in sphingomonads. The predicted substrate
      specificities, derived from the phylogenetic relationship of each of the RHOs,
      were examined based on transformation of putative substrates and their structural
      homologs by the recombinant strains expressing each of the oxygenases and the
      sole set of available ET proteins. The RHO AhdA1bA2b was functionally
      characterized for the first time and was found to be capable of transforming
      ethylbenzene, propylbenzene, cumene, p-cymene and biphenyl, in addition to a
      number of polycyclic aromatic hydrocarbons. Overexpression of aromatic catabolic
      genes in strain PNB, revealed by real-time PCR analyses, is a way forward to
      understand the complex regulation of degradative genes in sphingomonads. 

PMID- 24918042
TI  - The role of autophagy in the intracellular survival of Campylobacter concisus.
AB  - Campylobacter concisus is an emerging pathogen that has been associated with
      gastrointestinal diseases. Given the importance of autophagy for the elimination
      of intracellular bacteria and the subversion of this process by pathogenic
      bacteria, we investigated the role of autophagy in C. concisus intracellular
      survival. Gentamicin protection assays were employed to assess intracellular
      levels of C. concisus within Caco-2 cells, following autophagy induction and
      inhibition. To assess the interaction between C. concisus and autophagosomes,
      confocal microscopy, scanning electron microscopy, and transmission electron
      microscopy were employed. Expression levels of 84 genes involved in the autophagy
      process were measured using qPCR. Autophagy inhibition resulted in two- to four
      fold increases in intracellular levels of C. concisus within Caco-2 cells, while
      autophagy induction resulted in a significant reduction in intracellular levels
      or bacterial clearance. C. concisus strains with low intracellular survival
      levels showed a dramatic increase in these levels upon autophagy inhibition.
      Confocal microscopy showed co-localization of the bacterium with autophagosomes,
      while transmission electron microscopy identified intracellular bacteria
      persisting within autophagic vesicles. Further, qPCR showed that following
      infection, 13 genes involved in the autophagy process were significantly
      regulated, and a further five showed borderline results, with an overall
      indication towards a dampening effect exerted by the bacterium on this process.
      Our data collectively indicates that while autophagy is important for the
      clearance of C. concisus, some strains may manipulate this process to benefit
      their intracellular survival. 

PMID- 24918043
TI  - A word of caution about biological inference - Revisiting cysteine covalent state
      predictions.
AB  - The success of methods for predicting the redox state of cysteine residues from
      the sequence environment seemed to validate the basic assumption that this state
      is mainly determined locally. However, the accuracy of predictions on randomized
      sequences or of non-cysteine residues remained high, suggesting that these
      predictions rather capture global features of proteins such as subcellular
      localization, which depends on composition. This illustrates that even high
      prediction accuracy is insufficient to validate implicit assumptions about a
      biological phenomenon. Correctly identifying the relevant underlying biochemical
      reasons for the success of a method is essential to gain proper biological
      insights and develop more accurate and novel bioinformatics tools. 

PMID- 24918044
TI  - The role of Cysteine 227 in subcellular localization, water permeability, and
      multimerization of aquaporin-11.
AB  - Aquaporin-11 (AQP11) is the latest member of the mammalian water channel protein
      family to be described. Recent in vivo studies have shown that mutation at
      Cys(227) causes renal failure. However the importance of Cys(227) for the
      molecular function of AQP11 is largely unknown. In this study, we examined the
      subcellular localization, water permeability, and multimerization of AQP11 with a
      mutation at Cys(227). Interestingly, cells expressing the mutants had
      significantly higher osmotic water permeability. In contrast, the mutation
      lowered the cell surface expression and multimerization levels. Our observations
      suggest that Cys(227) is crucial for the proper molecular function of AQP11. 

PMID- 24918045
TI  - Mutation G805R in the transmembrane domain of the LDL receptor gene causes
      familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor
      in the endoplasmic reticulum.
AB  - More than 1700 mutations in the low density lipoprotein receptor (LDLR) gene have
      been found to cause familial hypercholesterolemia (FH). These are commonly
      divided into five classes based upon their effects on the structure and function
      of the LDLR. However, little is known about the mechanism by which mutations in
      the transmembrane domain of the LDLR gene cause FH. We have studied how the
      transmembrane mutation G805R affects the function of the LDLR. Based upon Western
      blot analyses of transfected HepG2 cells, mutation G805R reduced the amounts of
      the 120 kDa precursor LDLR in the endoplasmic reticulum. This led to reduced
      amounts of the mature 160 kDa LDLR at the cell surface. However, significant
      amounts of a secreted 140 kDa G805R-LDLR ectodomain fragment was observed in the
      culture media. Treatment of the cells with the metalloproteinase inhibitor
      batimastat largely restored the amounts of the 120 and 160 kDa forms in cell
      lysates, and prevented secretion of the 140 kDa ectodomain fragment. Together,
      these data indicate that a metalloproteinase cleaved the ectodomain of the 120
      kDa precursor G805R-LDLR in the endoplasmic reticulum. It was the presence of the
      polar Arg805 and not the lack of Gly805 which led to ectodomain cleavage. Arg805
      also prevented gamma-secretase cleavage within the transmembrane domain. It is
      conceivable that introducing a charged residue within the hydrophobic membrane
      lipid bilayer, results in less efficient incorporation of the 120 kDa G805R-LDLR
      in the endoplasmic reticulum membrane and makes it a substrate for
      metalloproteinase cleavage. 

PMID- 24918047
TI  - Establishment of a mast cell line, NCL-2, without Kit mutation, derived from NC
      mouse bone marrow.
AB  - Immortal mast cell lines, such as RBL-2H3 and HMC-1 cells, are commonly utilized
      to investigate the function of mast cells. However, they are tumor cells carrying
      a gain-of-function mutation of Kit. We established an immortal mast cell line
      without Kit mutation, NCL-2, derived from NC mouse bone marrow. NCL-2 cells could
      be maintained without additional growth factors and thus could respond to
      exogenous growth signals. Moreover, NCL-2 cells expressed FcepsilonRI and KIT,
      and release histamine and LTB4 in response to antigen stimulation. This cell line
      could be a useful tool to analyze proliferation, differentiation, and function of
      normal mast cells. 

PMID- 24918046
TI  - Inhibition of malignant phenotypes of human osteosarcoma cells by a gene
      silencer, a pyrrole-imidazole polyamide, which targets an E-box motif.
AB  - Gene amplification and/or overexpression of the transcription factor c-MYC, which
      binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human
      tumors. In this study, we have designed 5 pyrrole-imidazole (PI) polyamides
      recognizing E-box, and found that, among them, Myc-6 significantly suppresses
      malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo.
      Intriguingly, knockdown of the putative Myc-6 target MALAT1 encoding long
      noncoding RNA remarkably impaired cell growth of MG63 cells. Collectively, our
      present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability
      at least in part through the specific down-regulation of MALAT1. 

PMID- 24918048
TI  - The effects of the heme precursor 5-aminolevulinic acid (ALA) on REV-ERBalpha
      activation.
AB  - The nuclear receptor, REV-ERBalpha, has a key role in circadian rhythms and
      requires heme as its ligand. The present study determined whether the heme
      precursor, 5-aminolevulinic acid (ALA), affects REV-ERBalpha and its target
      genes. When exposed to ALA, the human lung diploid cell line, WI-38, exhibited
      activation of REV-ERBalpha and repression of the transcription of REV-ERBalpha
      target genes, including BMAL1, an essential component of the circadian
      oscillator. Moreover, co-incubation of sodium ferrous citrate (SFC) and ALA also
      activated REV-ERBalpha and repressed the transcription of REV-ERBalpha target
      genes. These results indicate that ALA regulates human circadian rhythms via REV
      ERBalpha. 

PMID- 24918050
TI  - Interaction of Sesbania mosaic virus (SeMV) RNA-dependent RNA polymerase (RdRp)
      with the p10 domain of polyprotein 2a and its implications in SeMV replication.
AB  - Identification of viral encoded proteins that interact with RNA-dependent RNA
      polymerase (RdRp) is an important step towards unraveling the mechanism of
      replication. Sesbania mosaic virus (SeMV) RdRp was shown to interact strongly
      with p10 domain of polyprotein 2a and moderately with the protease domain.
      Mutational analysis suggested that the C-terminal disordered domain of RdRp is
      involved in the interaction with p10. Coexpression of full length RdRp and p10
      resulted in formation of RdRp-p10 complex which showed significantly higher
      polymerase activity than RdRp alone. Interestingly, CDelta43 RdRp also showed a
      similar increase in activity. Thus, p10 acts as a positive regulator of RdRp by
      interacting with the C-terminal disordered domain of RdRp. 

PMID- 24918049
TI  - Staphylococcal nuclease domain containing-1 (SND1) promotes migration and
      invasion via angiotensin II type 1 receptor (AT1R) and TGFbeta signaling.
AB  - Staphylococcal nuclease domain containing-1 (SND1) is overexpressed in human
      hepatocellular carcinoma (HCC) patients and promotes tumorigenesis by human HCC
      cells. We now document that SND1 increases angiotensin II type 1 receptor (AT1R)
      levels by increasing AT1R mRNA stability. This results in activation of ERK,
      Smad2 and subsequently the TGFbeta signaling pathway, promoting epithelial
      mesenchymal transition (EMT) and migration and invasion by human HCC cells. A
      positive correlation was observed between SND1 and AT1R expression levels in
      human HCC patients. Small molecule inhibitors of SND1, alone or in combination
      with AT1R blockers, might be an effective therapeutic strategy for late-stage
      aggressive HCC. 

PMID- 24918051
TI  - CD9 may contribute to the survival of human germinal center B cells by
      facilitating the interaction with follicular dendritic cells.
AB  - The germinal center (GC) is a dynamic microenvironment where antigen (Ag)
      activated B cells rapidly expand and differentiate, generating plasma cells (PC)
      that produce high-affinity antibodies. Precise regulation of survival and
      proliferation of Ag-activated B cells within the GC is crucial for humoral immune
      responses. The follicular dendritic cells (FDC) are the specialized stromal cells
      in the GC that prevent apoptosis of GC-B cells. Recently, we reported that human
      GC-B cells consist of CD9+ and CD9- populations and that it is the CD9+ cells
      that are committed to the PC lineage. In this study, we investigated the
      functional role of CD9 on GC-B cells. Tonsillar tissue section staining revealed
      that in vivo CD9+ GC-B cells localized in the light zone FDC area. Consistent
      this, in vitro CD9+ GC-B cells survived better than CD9- GC-B cells in the
      presence of HK cells, an FDC line, in a cell-cell contact-dependent manner. The
      frozen tonsillar tissue section binding assay showed that CD9+ GC-B cells bound
      to the GC area of tonsillar tissues significantly more than the CD9- GC-B cells
      did and that the binding was significantly inhibited by neutralizing anti
      integrin beta1 antibody. Furthermore, CD9+ cells bound to soluble VCAM-1 more
      than CD9- cells did, resulting in activation and stabilization of the active
      epitope of integrin beta1. All together, our data suggest that CD9 on GC-B cells
      contributes to survival by strengthening their binding to FDC through the
      VLA4/VCAM-1 axis. 

PMID- 24918052
TI  - Fructose 1-phosphate is the one and only physiological effector of the Cra (FruR)
      regulator of Pseudomonas putida.
AB  - Fructose-1-phosphate (F1P) is the preferred effector of the catabolite
      repressor/activator (Cra) protein of the soil bacterium Pseudomonas putida but
      its ability to bind other metabolic intermediates in vivo is unclear. The Cra
      protein of this microorganism (Cra(PP)) was submitted to mobility shift assays
      with target DNA sequences (the PfruB promoter) and candidate effectors fructose
      1,6-bisphosphate (FBP), glucose 6-phosphate (G6P), and fructose-6-phosphate
      (F6P). 1 mM F1P was sufficient to release most of the Cra protein from its
      operators but more than 10 mM of FBP or G6P was required to free the same
      complex. However, isothermal titration microcalorimetry failed to expose any
      specific interaction between Cra(PP) and FBP or G6P. To solve this paradox,
      transcriptional activity of a PfruB-lacZ fusion was measured in wild-type and
      DeltafruB cells growing on substrates that change the intracellular
      concentrations of F1P and FBP. The data indicated that PfruB activity was
      stimulated by fructose but not by glucose or succinate. This suggested that
      Cra(PP) represses expression in vivo of the cognate fruBKA operon in a fashion
      dependent just on F1P, ruling out any other physiological effector. Molecular
      docking and dynamic simulations of the Cra-agonist interaction indicated that
      both metabolites can bind the repressor, but the breach in the relative affinity
      of Cra(PP) for F1P vs FBP is three orders of magnitude larger than the equivalent
      distance in the Escherichia coli protein. This assigns the Cra protein of P.
      putida the sole role of transducing the presence of fructose in the medium into a
      variety of direct and indirect physiological responses. 

PMID- 24918053
TI  - EF-hand motifs of diacylglycerol kinase alpha interact intra-molecularly with its
      C1 domains.
AB  - Diacylglycerol kinase (DGK) alpha, which is activated by Ca(2+), contains a
      recoverin homology (RVH) domain, tandem repeats of two Ca(2+)-binding EF-hand
      motifs, two cysteine-rich C1 domains and the catalytic domain. We previously
      found that a DGKalpha mutant lacking the RVH domain and EF-hands was
      constitutively active and that the N-terminal region of DGKalpha, consisting of
      the RVH domain and EF-hand motifs, interacted intra-molecularly with the C
      terminal region containing the C1 and catalytic domains. In this study, we
      narrowed down the interaction regions of DGKalpha. At the C-terminal region, the
      C1 domains are responsible for the intra-molecular interaction. At the N-terminal
      region, the EF-hand motifs mainly contribute to the interaction. Moreover, using
      highly purified EF-hand motifs and C1 domains, we demonstrate that they directly
      bind to each other. The co-precipitation of these two domains was clearly
      attenuated by the addition of Ca(2+). These results indicate that the Ca(2+)
      induced dissociation of the intra-molecular interaction between the EF-hand
      motifs and the C1 domains of DGKalpha is the key event that regulates the
      activity of the enzyme. 

PMID- 24918054
TI  - Changed membrane integration and catalytic site conformation are two mechanisms
      behind the increased Abeta42/Abeta40 ratio by presenilin 1 familial Alzheimer
      linked mutations.
AB  - The enzyme complex gamma-secretase generates amyloid beta-peptide (Abeta), a 37
      43-residue peptide associated with Alzheimer disease (AD). Mutations in
      presenilin 1 (PS1), the catalytical subunit of gamma-secretase, result in
      familial AD (FAD). A unifying theme among FAD mutations is an alteration in the
      ratio Abeta species produced (the Abeta42/Abeta40 ratio), but the molecular
      mechanisms responsible remain elusive. In this report we have studied the impact
      of several different PS1 FAD mutations on the integration of selected PS1
      transmembrane domains and on PS1 active site conformation, and whether any
      effects translate to a particular amyloid precursor protein (APP) processing
      phenotype. Most mutations studied caused an increase in the Abeta42/Abeta40
      ratio, but via different mechanisms. The mutations that caused a particular large
      increase in the Abeta42/Abeta40 ratio did also display an impaired APP
      intracellular domain (AICD) formation and a lower total Abeta production.
      Interestingly, seven mutations close to the catalytic site caused a severely
      impaired integration of proximal transmembrane/hydrophobic sequences into the
      membrane. This structural defect did not correlate to a particular APP processing
      phenotype. Six selected FAD mutations, all of which exhibited different APP
      processing profiles and impact on PS1 transmembrane domain integration, were
      found to display an altered active site conformation. Combined, our data suggest
      that FAD mutations affect the PS1 structure and active site differently,
      resulting in several complex APP processing phenotypes, where the most aggressive
      mutations in terms of increased Abeta42/Abeta40 ratio are associated with a
      decrease in total gamma-secretase activity. 

PMID- 24918056
TI  - Identification of a truncated kinase suppressor of Ras 2 mRNA in sperm.
AB  - The kinase suppressor of Ras 2 (KSR2) is a scaffold protein for the extracellular
      signal-regulated protein kinase (ERK) signaling pathway. KSR2 mediates germline
      mpk-1 (Caenorhabditis elegans ERK) phosphorylation in C. elegans and has been
      implicated the regulation of meiosis. KSR2(-/-) mice exhibit metabolic
      abnormalities and are reproductively impaired. The role of KSR2 in meiosis and
      fertility in mice has yet to be elucidated. Here, we describe a novel truncated
      KSR2 mRNA identified in mouse testes (T-KSR2). Further analysis demonstrates T
      KSR2 is specific to mouse testes and mature sperm cells. The detection of T-KSR2
      may enhance our understanding of mechanisms controlling spermatogenesis and
      fertility. 

PMID- 24918055
TI  - CK2 phosphorylation of human centrins 1 and 2 regulates their binding to the DNA
      repair protein XPC, the centrosomal protein Sfi1 and the phototransduction
      protein transducin beta.
AB  - Centrins are calcium-binding proteins that can interact with several cellular
      targets (Sfi1, XPC, Sac3 and transducin beta) through the same hydrophobic triad.
      However, two different orientations of the centrin-binding motif have been
      observed: W(1)xxL(4)xxxL(8) for XPC (xeroderma pigmentosum group C protein) and
      the opposite orientation L(8)xxxL(4)xxW(1) for Sfi1 (suppressor of fermentation
      induced loss of stress resistance protein 1), Sac3 and transducin beta. Centrins
      are also phosphorylated by several protein kinases, among which is CK2. The
      purpose of this study was to determine the binding mechanism of human centrins to
      three targets (transducin beta, Sfi1 and XPC), and the effects of in vitro
      phosphorylation by CK2 of centrins 1 and 2 with regard to this binding mechanism.
      We identified the centrin-binding motif at the COOH extremity of transducin beta.
      Human centrin 1 binds to transducin beta only in the presence of calcium with a
      binding constant lower than the binding constant observed for Sfi1 and for XPC.
      The affinity constants of centrin 1 were 0.10 10(6) M(-1), 249 10(6) M(-1) and
      52.5 10(6) M(-1) for Trd, R17-Sfi1 and P17-XPC respectively. CK2 phosphorylates
      human centrin 1 at residue T138 and human centrin 2 at residues T138 and S158.
      Consequently CK2 phosphorylation abolished the binding of centrin 1 to transducin
      beta and reduced the binding to Sfi1 and XPC. CK2 phosphorylation of centrin 2 at
      T138 and S158 abolished the binding to Sfi1 as assessed using a C-HsCen2 T138D
      S158D phosphomimetic form of centrin 2. 

PMID- 24918057
TI  - Elucidating the host-pathogen interaction between human colorectal cells and
      invading Enterovirus 71 using transcriptomics profiling.
AB  - Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and
      Mouth Disease (HFMD) and has been shown to be associated with severe clinical
      manifestation. Currently, there is no antiviral therapeutic for the treatment of
      HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study
      seeks to elucidate the transcriptomic changes that result from EV71 infection.
      Human whole genome microarray was employed to monitor changes in genomic profiles
      between infected and uninfected cells. The results reveal altered expression of
      human genes involved in critical pathways including the immune response and the
      stress response. Together, data from this study provide valuable insights into
      the host-pathogen interaction between human colorectal cells and EV71. 

PMID- 24918058
TI  - Biophysical analysis of the interaction of the serum protein human beta2GPI with
      bacterial lipopolysaccharide.
AB  - There are several human serum proteins for which no clear role is yet known.
      Among these is the abundant serum protein beta2-glycoprotein-I (beta2GPI), which
      is known to bind to negatively charged phospholipids as well as to bacterial
      lipopolysaccharides (LPS), and was therefore proposed to play a role in the
      immune response. To understand the details of these interactions, a biophysical
      analysis of the binding of beta2GPI to LPS and phosphatidylserine (PS) was
      performed. The data indicate only a moderate tendency of the protein (1) to
      influence the LPS-induced cytokine production in vitro, (2) to react exothermally
      with LPS in a non-saturable way, and (3) to change its local microenvironment
      upon LPS association. Additionally, we found that the protein binds more strongly
      to phosphatidylserine (PS) than to LPS. Furthermore, beta2GPI converts the LPS
      bilayer aggregates into a stronger multilamellar form, and reduces the fluidity
      of the hydrocarbon moiety of LPS due to a rigidification of the acyl chains. From
      these data it can be concluded that beta2GPI plays a role as an immune-modulating
      agent, but there is much less evidence for a role in immune defense against
      bacterial toxins such as LPS. 

PMID- 24918059
TI  - Small RNA expression and deep sequencing analyses of the nucleolus reveal the
      presence of nucleolus-associated microRNAs.
AB  - Micro RNAs (miRNA) are non-coding RNAs expressed in the cytoplasm as their
      mature, 21-22-nucleotide short forms. More recently, mature miRNAs have also been
      detected in the nucleus, raising the possibility that their spatial distribution
      may be more complex than anticipated. Here we undertook comprehensive systematic
      analyses of miRNA distribution in several subcellular compartments of human
      cancer cells. In particular, we focused on the potential presence of miRNAs in
      the nucleolus, which contains an abundance of small non-coding RNAs. We employed
      two miRNA expression array platforms and small RNA deep sequencing of small RNAs
      isolated from cells, nuclei, cytoplasm and the nucleoli. We developed an assay to
      compare RNAs of isolated nucleoli before and after denaturation and used Northern
      hybridization to verify the presence of miRNAs in the subcellular compartments.
      Consistently, we found more than 10 miRNAs associated with the nucleolar
      preparations. Several miRNAs had greater relative abundance in the nucleolus
      compared to the other compartments. The nucleolar presence of miRNAs was
      independent of Dicer and the main activity of the nucleolus, RNA polymerase I
      transcription, but was dependent on CRM1 previously associated with nucleolar
      trafficking of small nucleolar RNAs. These results highlight the complexity of
      miRNA spatial arrangement and regulation. 

PMID- 24918060
TI  - The levels of RAC3 expression are up regulated by TNF in the inflammatory
      response.
AB  - RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-kappaB (NF
      kappaB) that is usually over-expressed in tumors and which also has important
      functions in the immune system. We investigated the role of the inflammatory
      response in the control of RAC3 expression levels in vivo and in vitro. We found
      that inflammation regulates RAC3 levels. In mice, sub-lethal doses of
      lipopolysaccharide induce the increase of RAC3 in spleen and the administration
      of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar
      effect. However, the simultaneous treatment with both stimuli is mutually
      antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis
      factor (TNF), one of the cytokines induced by lipopolysaccharide, also increases
      the levels of RAC3 mRNA and protein, which correlates with an enhanced
      transcription dependent on the RAC3 gene promoter. We found that binding of the
      transcription factor NF-kappaB to the RAC3 gene promoter could be responsible for
      these effects. Our results suggest that increase of RAC3 during the inflammatory
      response could be a molecular mechanism involved in the control of sensitivity to
      both pro- and anti-inflammatory stimuli in order to maintain the normal healthy
      course of the immune response. 

PMID- 24918061
TI  - Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates
      chemosensitivity in human hepatocellular cancer.
AB  - Hepatocellular cancers (HCC) are highly resistant to chemotherapy. TGFbeta has
      been associated with chemoresistance in some human cancers but the mechanisms
      involved are unknown. We explored how TGFbeta might contribute to altered
      responses to therapy by assessing the involvement and mechanistic contribution of
      extracellular vesicle long non-coding RNA (lncRNA) in mediating TGFbeta-dependent
      chemoresistance. TGFbeta reduced the sensitivity of HCC cells to sorafenib or
      doxorubicin and altered the release of both extracellular vesicles and of
      selected lncRNA within these vesicles. Amongst these, lincRNA-ROR (linc-ROR), a
      stress-responsive lncRNA was highly expressed in HCC cells and enriched within
      extracellular vesicles derived from tumor cells. Incubation with HCC-derived
      extracellular vesicles increased linc-ROR expression and reduced chemotherapy
      induced cell death in recipient cells. Sorafenib increased linc-ROR expression in
      both tumor cells and extracellular vesicles, whereas siRNA to linc-ROR increased
      chemotherapy-induced apoptosis and cytotoxicity. Tumor-initiating cells that
      express CD133 have an increased resistance to therapy. TGFbeta increased
      expression of CD133+ cells and colony growth in limiting dilution assays, both of
      which were attenuated by linc-ROR knockdown. These data provide mechanistic
      insights into primary chemoresistance in HCC by showing that: (a) TGFbeta
      selectively enriches linc-RoR within extracellular vesicles, which has a
      potential role in intercellular signaling in response to TGFbeta; (b) expression
      and enrichment of linc-ROR during chemotherapeutic stress plays a functional role
      in chemoresistance; and (c) the effects of TGFbeta on chemoresistance in HCC may
      involve linc-RoR-dependent effects on tumor-initiating cells. These findings
      implicate extracellular vesicle lncRNA as mediators of the chemotherapeutic
      response, and support targeting linc-ROR to enhance chemosensitivity in HCC. 

PMID- 24918063
TI  - Inhibitors of the Cdc34 acidic loop: A computational investigation integrating
      molecular dynamics, virtual screening and docking approaches.
AB  - Among the different classes of enzymes involved in the ubiquitin pathway, E2
      ubiquitin-conjugating enzymes occupy a central role in the ubiquitination
      cascade. Cdc34-like E2 enzymes are characterized by a 12-14 residue insertion in
      the proximity of the catalytic site, known as the acidic loop. Cdc34 ubiquitin
      charging activity is regulated by CK2-dependent phosphorylation and the
      regulatory mechanism involves the acidic loop. Indeed, the phosphorylation
      stabilizes the loop in an open conformation that is competent for ubiquitin
      charging. Cdc34 is associated with a variety of diseases, such as hepatocellular
      carcinomas and prostatic adenocarcinomas. In light of its role, the discovery of
      potential inhibitory compounds would provide the mean to effectively modulate its
      activity. Here, we carried out a computational study based on molecular dynamics,
      virtual screening and docking to identify potential inhibitory compounds of
      Cdc34, modulating the acidic loop conformation. The molecules identified in this
      study have been designed to act as molecular hinges that can bind the acidic loop
      in its closed conformation, thus inhibiting the Cdc34-mediated ubiquitination
      cascade at the ubiquitin-charging step. In particular, we proposed a
      pharmacophore model featuring two amino groups in the central part of the model
      and two lateral aromatic chains, which respectively establish electrostatic
      interactions with the acidic loop (Asp 108 and Glu 109) and a hydrogen bond with
      Ser 139, which is one of the key residues for Cdc34 activity. 

PMID- 24918062
TI  - Campylobacter jejuni gene cj0511 encodes a serine peptidase essential for
      colonisation.
AB  - According to MEROPS peptidase database, Campylobacter species encode 64 predicted
      peptidases. However, proteolytic properties of only a few of these proteins have
      been confirmed experimentally. In this study we identified and characterised a
      Campylobacter jejuni gene cj0511 encoding a novel peptidase. The proteolytic
      activity associated with this enzyme was demonstrated in cell lysates. Moreover,
      enzymatic studies conducted with a purified protein confirmed a prediction of it
      being a serine peptidase. Furthermore, cj0511 mutant was found to be severely
      attenuated in chicken colonisation model, suggesting a role of the Cj0511 protein
      in infection. 

PMID- 24918064
TI  - Acute leukemia of ambiguous lineage with trisomy 4 as the sole cytogenetic
      abnormality: A case report and literature review.
AB  - We describe a patient with acute leukemia of ambiguous lineage who had trisomy 4
      as the sole cytogenetic abnormality. Clinical, pathological, immunophenotypic and
      molecular features are presented and compared with the previous 4 published
      cases. Over expression of c-kit, which is localized to chromosome 4, was
      documented on the leukemic blasts. Prognosis seems to be poor. Treatment with
      acute lymphoblastic leukemia like regimens seems to be superior compared to acute
      myeloid leukemia like regimens and allogeneic stem cell transplant is recommended
      after achieving remission. 

PMID- 24918065
TI  - Cardiac anaplastic large cell lymphoma in an 8-year old boy.
AB  - We report on an 8 year old boy with primary cardiac anaplastic large cell
      lymphoma (ALCL), in whom the diagnosis was challenging and who was treated with
      modified chemotherapy without radiation therapy according to the ALCL 99 study
      protocol [1]. Two years and 4 months after completion of therapy the boy is in
      complete remission with normal cardiac function. 

PMID- 24918066
TI  - Acute myeloid leukemia arising from a donor derived premalignant hematopoietic
      clone: A possible mechanism for the origin of leukemia in donor cells.
AB  - During recent years, it has become increasingly evident that donor leukemia
      following allogeneic transplant may be more common then realized in the past. We
      identified five cases of potential donor leukemia cases during past five years.
      The precise mechanism of the origin of such leukemias, however, remains poorly
      defined. In this short communication, we report a well documented case of donor
      derived de novo acute myeloid leukemia (AML) that developed fourteen years after
      allogeneic stem cell transplantation for treatment induced AML for his primary
      malignancy Immunoblastic lymphoma. This case allows us to postulate a possible
      mechanism of the origin of donor leukemia. The de novo AML clone contained a
      distinct cytogenetic abnormality, trisomy 11, which was simultaneously detected
      in preserved peripheral blood obtained at the time of transplantation as well as
      in the current bone marrow from an otherwise clinically and phenotypically normal
      donor. The findings from this unique case, provides insight into the process of
      leukemogenesis, and suggests that the sequence of events leading to
      leukemogenesis in this patient involved the senescence/apoptosis of normal donor
      hematopoietic cells due to telomere shortening resulting in the selective
      proliferation and transformation of this clone with MLL (mixed-lineage leukemia)
      gene amplification. 

PMID- 24918067
TI  - Emotional bias of cognitive control in adults with childhood attention
      deficit/hyperactivity disorder.
AB  - Affect recognition deficits found in individuals with attention
      deficit/hyperactivity disorder (ADHD) across the lifespan may bias the
      development of cognitive control processes implicated in the pathophysiology of
      the disorder. This study aimed to determine the mechanism through which facial
      expressions influence cognitive control in young adults diagnosed with ADHD in
      childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with
      no history of ADHD were scanned with functional magnetic resonance imaging while
      performing a face emotion go/no-go task. Event-related analyses contrasted
      activation and functional connectivity for cognitive control collapsed over face
      valence and tested for variations in activation for response execution and
      inhibition as a function of face valence. Probands with childhood ADHD made fewer
      correct responses and inhibitions overall than comparison subjects, but
      demonstrated comparable effects of face emotion on response execution and
      inhibition. The two groups showed similar frontotemporal activation for cognitive
      control collapsed across face valence, but differed in the functional
      connectivity of the right dorsolateral prefrontal cortex, with fewer interactions
      with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in
      probands than in comparison subjects. Further, valence-dependent activation for
      response execution was seen in the amygdala, ventral striatum, subgenual
      cingulate cortex, and orbitofrontal cortex in comparison subjects but not in
      probands. The findings point to functional anomalies in limbic networks for both
      the valence-dependent biasing of cognitive control and the valence-independent
      cognitive control of face emotion processing in probands with childhood ADHD.
      This limbic dysfunction could impact cognitive control in emotional contexts and
      may contribute to the social and emotional problems associated with ADHD. 

PMID- 24918068
TI  - Multimodal evidence of regional midcingulate gray matter volume underlying
      conflict monitoring.
AB  - Functional neuroimaging studies have long implicated the mid-cingulate cortex
      (MCC) in conflict monitoring, but it is not clear whether its structural
      integrity (i.e., the gray matter volume) influences its conflict monitoring
      function. In this multimodal study, we used T1-weighted MRI scans as well as
      event-related potentials (ERPs) to test whether the MCC gray matter volume is
      associated with the electrocortical marker (i.e., No-go N200 ERP component) of
      conflict monitoring in healthy individuals. The specificity of such a
      relationship in health was determined in two ways: by (A) acquiring the same data
      from individuals with cocaine use disorder (CUD), known to have deficits in
      executive function including behavioral monitoring; and (B) acquiring the P300
      ERP component that is linked with attention allocation and not specifically with
      conflict monitoring. Twenty-five (39.1 +/- 8.4 years; 8 females) healthy
      individuals and 25 (42.7 +/- 5.9 years; 6 females) individuals with CUD underwent
      a rewarded Go/No-go task during which the ERP data was collected, and they also
      underwent a structural MRI scan. The whole brain regression analysis showed a
      significant correlation between MCC structural integrity and the well-known ERP
      measure of conflict monitoring (N200, but not the P300) in healthy individuals,
      which was absent in CUD who were characterized by reduced MCC gray matter volume,
      N200 abnormalities as well as reduced task accuracy. In individuals with CUD
      instead, the N200 amplitude was associated with drug addiction symptomatology.
      These results show that the integrity of MCC volume is directly associated with
      the electrocortical correlates of conflict monitoring in healthy individuals, and
      such an association breaks down in psychopathologies that impact these brain
      processes. Taken together, this MCC-N200 association may serve as a biomarker of
      improved behavioral monitoring processes in diseased populations. 

PMID- 24918070
TI  - Reducing sampling error in faecal egg counts from black rhinoceros (Diceros
      bicornis).
AB  - Faecal egg counts (FECs) are commonly used for the non-invasive assessment of
      parasite load within hosts. Sources of error, however, have been identified in
      laboratory techniques and sample storage. Here we focus on sampling error. We
      test whether a delay in sample collection can affect FECs, and estimate the
      number of samples needed to reliably assess mean parasite abundance within a host
      population. Two commonly found parasite eggs in black rhinoceros (Diceros
      bicornis) dung, strongyle-type nematodes and Anoplocephala gigantea, were used.
      We find that collection of dung from the centre of faecal boluses up to six hours
      after defecation does not affect FECs. More than nine samples were needed to
      greatly improve confidence intervals of the estimated mean parasite abundance
      within a host population. These results should improve the cost-effectiveness and
      efficiency of sampling regimes, and support the usefulness of FECs when used for
      the non-invasive assessment of parasite abundance in black rhinoceros
      populations. 

PMID- 24918071
TI  - Phoretic interaction between the kangaroo leech Marsupiobdella africana
      (Hirudinea: Glossiphoniidae) and the cape river crab Potamonautes perlatus
      (Decapoda: Potamonautidae).
AB  - The South African leech Marsupiobdella africana is a temporary ectoparasite of
      the amphibian Xenopus laevis, has a phoretic association with a freshwater crab
      Potamonautes perlatus, and exhibits advanced parental care by incubating its
      offspring in a brood pouch. Because phoretic associations are usually regarded to
      favor the phoront's dispersion, its occurrence within the biology of a parasitic
      species reflects an intimate context of interactions. In addition to phoresy,
      attachment to the crab may confer other advantages pertaining to offspring
      development and predator avoidance, dispersion and the parasitic life cycle. Two
      ponds where amphibian and crab hosts co-occur were sampled twice a month for a
      period of 1 year. The population dynamics of the leeches and their use of
      specific microhabitats as attachment sites on the crabs were also investigated.
      Results indicate a direct relationship between intra-specific variation in the
      sex ratio among captured crab hosts and the number of leeches recruited over
      time. The attachments to specific microhabitats on the hard surfaces of the host
      suggest a proximal proximate anti-predatory strategy. Finally, the importance of
      oxygen accessibility for the offspring development has been investigated
      experimentally. Results revealed a remarkable network of interactions linking all
      partners of this system raising the question as to whether the crabs merely act
      as a vehicle or play a role within the parasitic life cycle. 

PMID- 24918069
TI  - Effects of prenatal alcohol exposure on the development of white matter volume
      and change in executive function.
AB  - Prenatal alcohol exposure can cause a wide range of deficits in executive
      function that persist throughout life, but little is known about how changes in
      brain structure relate to cognition in affected individuals. In the current
      study, we predicted that the rate of white matter volumetric development would be
      atypical in children with fetal alcohol spectrum disorders (FASD) when compared
      to typically developing children, and that the rate of change in cognitive
      function would relate to differential white matter development between groups.
      Data were available for 103 subjects [49 with FASD, 54 controls, age range 6-17,
      mean age = 11.83] with 153 total observations. Groups were age-matched.
      Participants underwent structural magnetic resonance imaging (MRI) and an
      executive function (EF) battery. Using white matter volumes measured bilaterally
      for frontal and parietal regions and the corpus callosum, change was predicted by
      modeling the effects of age, intracranial volume, sex, and interactions with
      exposure status and EF measures. While both groups showed regional increases in
      white matter volumes and improvement in cognitive performance over time, there
      were significant effects of exposure status on age-related relationships between
      white matter increases and EF measures. Specifically, individuals with FASD
      consistently showed a positive relationship between improved cognitive function
      and increased white matter volume over time, while no such relationships were
      seen in controls. These novel results relating improved cognitive function with
      increased white matter volume in FASD suggest that better cognitive outcomes
      could be possible for FASD subjects through interventions that enhance white
      matter plasticity. 

PMID- 24918072
TI  - Angiostrongylus vasorum in wolves in Italy.
AB  - In the past decade, the parasitic nematode Angiostrongylus vasorum has attracted
      attention for its emergence in previously free areas and for the rise in clinical
      cases in domestic dogs. Italy is regarded as one of the countries where this
      potentially life-threatening parasite is spreading, especially due to bridging
      infections between wildlife and domestic dogs. The present article describes the
      presence of A. vasorum in wolves from Italy. Nematodes were observed in
      histological sections of three wolves found dead in Rome province, central Italy.
      Morphological and molecular identification of the nematodes, by polymerase chain
      reaction of rDNA ITS-2 and sequencing, confirmed the nematodes to be A. vasorum,
      with 99% genetic homology with A. vasorum from sympatric dogs. This is the second
      report of this species in wolves and the first in this host in Italy, and
      coincides with increasing records of A. vasorum in dogs and foxes in Italy.
      Implications for the epidemiology of this emerging parasite and for wildlife
      health are concisely discussed. 

PMID- 24918073
TI  - Use of filter papers to determine seroprevalence of Toxoplasma gondii among
      hunted ungulates in remote Peruvian Amazon.
AB  - Toxoplasmosis is a zoonosis caused by the protozoan Toxoplasma gondii, and it is
      found worldwide. To determine whether ungulates are reservoirs of T. gondii in an
      isolated and remote region of the northeastern Peruvian Amazon, antibodies to T.
      gondii were determined in 5 species of ungulates by the modified agglutination
      test (MAT). These animals were hunted by subsistence hunters along the Yavari
      Mirin River, in the northeastern Peruvian Amazon. Blood samples were collected by
      hunters on filter papers. For determination of T. gondii antibodies, blood was
      eluted from filter papers, and a titer of 1:25 was considered indicative of
      exposure to T. gondii. Antibodies to T. gondii were found in 26 (31.0%) peccaries
      (Pecari tajacu, Tayassu pecari), six (17.1%) brocket deer (Mazama americana,
      Mazama gouazoubira), and four (40.0%) lowland tapir (Tapirus terrestris). We also
      introduced a modification to the MAT protocol that allows the extraction of fluid
      samples from several types of laboratory-grade filter paper, thus enabling
      researchers to easily adapt their approaches to the materials presented to them. 

PMID- 24918074
TI  - Pentastomids of wild snakes in the Australian tropics.
AB  - Pentastomids are endoparasites of the respiratory system of vertebrates, maturing
      primarily in carnivorous reptiles. Adult and larval pentastomids can cause severe
      pathology resulting in the death of their intermediate and definitive hosts. The
      study of pentastomids is a neglected field, impaired by risk of zoonoses,
      difficulties in species identification, and life cycle complexities. We surveyed
      wild snakes in the tropics of Australia to clarify which host species possess
      these parasites, and then sought to identify these pentastomids using a
      combination of morphological and molecular techniques. We detected pentastomid
      infections in 59% of the 81 snakes surveyed. The ubiquity of pentastomid
      infections in snakes of the Australian tropics sampled in this study is
      alarmingly high considering the often-adverse consequences of infection and the
      recognized zoonotic potential of these parasites. The pentastomids were of the
      genera Raillietiella and Waddycephalus and infected a range of host taxa,
      encompassing seven snake species from three snake families. All seven snake
      species represent new host records for pentastomids of the genera Raillietiella
      and/or Waddycephalus. The arboreal colubrid Dendrelaphis punctulatus and the
      terrestrial elapid Demansia vestigiata had particularly high infection
      prevalences (79% and 100% infected, respectively). Raillietiella orientalis
      infected 38% of the snakes surveyed, especially frog-eating species, implying a
      frog intermediate host for this parasite. Raillietiella orientalis was previously
      known only from Asian snakes and has invaded Australia via an unknown pathway.
      Our molecular data indicated that five species of Waddycephalus infect 28% of
      snakes in the surveyed area. Our morphological data indicate that features of
      pentastomid anatomy previously utilised to identify species of the genus
      Waddycephalus are unreliable for distinguishing species, highlighting the need
      for additional taxonomic work on this genus. 

PMID- 24918075
TI  - Trichomonas stableri n. sp., an agent of trichomonosis in Pacific Coast band
      tailed pigeons (Patagioenas fasciata monilis).
AB  - Trichomonas gallinae is a ubiquitous flagellated protozoan parasite, and the most
      common etiologic agent of epidemic trichomonosis in columbid and passerine
      species. In this study, free-ranging Pacific Coast band-tailed pigeons
      (Patagioenas fasciata monilis) in California (USA) were found to be infected with
      trichomonad protozoa that were genetically and morphologically distinct from T.
      gallinae. In microscopic analysis, protozoa were significantly smaller in length
      and width than T. gallinae and were bimodal in morphology. Phylogenetic analysis
      of the ITS1/5.8S/ITS2, rpb1, and hydrogenosomal Fe-hydrogenase regions revealed
      that the protozoan shares an ancestor with Trichomonas vaginalis, the sexually
      transmitted agent of trichomoniasis in humans. Clinical and pathologic features
      of infected birds were similar to infections with T. gallinae. Evidence presented
      here strongly support taxonomical distinction of this parasite, which we hereby
      name Trichomonas stableri n. sp. This work contributes to a growing body of
      evidence that T. gallinae is not the sole etiologic agent of avian trichomonosis,
      and that the incorporation of molecular tools is critical in the investigation of
      infectious causes of mortality in birds. 

PMID- 24918077
TI  - Fertility preservation and potential future treatment options.

PMID- 24918076
TI  - Myxozoa in high Arctic: Survey on the central part of Svalbard archipelago.
AB  - Myxosporeans (Myxozoa), microscopic metazoan parasitic organisms, are poorly
      studied in the Arctic region. Our survey of benthic and pelagic fish (n = 234)
      collected in Isfjorden (Svalbard, Norway) together with detailed morphological
      and molecular examination revealed the presence of nine myxosporean species. We
      compared observed myxosporean diversity with diversity documented in regions
      close to the Arctic and revealed that water depth rather than geographic
      distribution is an important factor influencing myxosporean fauna. WE DESCRIBE
      THREE NEW MYXOSPOREAN SPECIES: Zschokkella siegfriedi n. sp. from kidney of
      Boreogadus saida, Parvicapsula petuniae n. sp. from the urinary bladder of
      Gymnocanthus tricuspis, and Sinuolinea arctica n. sp. from the urinary bladder of
      Myoxocephalus scorpius. We characterise Latyspora-like organism from kidney of
      Clupea harengus. We provide new data for Ceratomyxa porrecta, Myxidium gadi,
      Myxidium finnmarchicum, Schulmania aenigmatosa, and Parvicapsula irregularis
      comb. nov. The phylogenetic analyses including the newly obtained SSU and LSU
      rDNA data revealed that most of the species studied cluster in the marine urinary
      clade within the marine myxosporean lineage. Newly obtained sequences including
      the first molecular data for the member of the genus Schulmania, substantially
      enriched the Zschokkella subclade. C. porrecta and the two Myxidium species
      cluster within the Ceratomyxa and marine Myxidium clade, respectively. Newly
      described species, Z. siegfriedi n. sp., was revealed to be morphologically
      indistinguishable but genetically diverse from Zschokkella hildae known from
      numerous gadid fish. Therefore, we consider Z. siegfriedi to be a cryptic
      myxosporean species that might be misidentified with Z. hildae. A Latyspora-like
      organism was found to be taxonomically problematic due to its suture line and its
      distant phylogenetic position from the type species Latyspora scomberomori did
      not allow us to assign it to the genus Latyspora. Based on an increased taxon
      sampling and SSU + LSU rDNA-based phylogeny, evolutionary trends within the
      marine urinary clade are investigated.

PMID- 24918078
TI  - The Effect of Curcumin on Intracellular pH (pHi), Membrane Hyperpolarization and
      Sperm Motility.
AB  - BACKGROUND: Curcumin has shown to affect sperm motility and function in vitro and
      fertility in vivo. The molecular mechanism(s) by which curcumin affects sperm
      motility has not been delineated. Since modulation of intracellular pH (pHi) and
      plasma membrane polarization is involved in sperm motility, the present study was
      conducted to investigate the effect of curcumin on these sperm (human and murine)
      parameters. METHODS: The effect of curcumin on sperm forward motility was
      examined by counting percentages of forward moving sperm. The effect of curcumin
      on intracellular pH (pHi) was measured by the fluorescent pH indicator 2,7
      bicarboxyethyl-5,6-carboxyfluorescein-acetoxymethyl ester (BCECF-AM). The effect
      of curcumin on plasma membrane polarization was examined using the fluorescence
      sensitive dye bis (1,3-dibarbituric acid)-trimethine oxanol [DiBAC4(3)]. RESULTS:
      Curcumin caused a concentration-dependent (p<0.05) decrease in forward motility
      of both human and mouse sperm. It also caused a concentration-dependent decrease
      in intracellular pH (pHi) in both human and mouse sperm. Curcumin induced
      significant (p<0.05) hyperpolarization of the plasma membrane in both human and
      mouse sperm. CONCLUSION: These findings indicate that curcumin inhibits sperm
      forward motility by intracellular acidification and hyperpolarization of sperm
      plasma membrane. This is the first study to our knowledge which examined the
      effect of curcumin on sperm pHi and membrane polarization that affect sperm
      forward motility. These exciting findings will have application in deciphering
      the signal transduction pathway involved in sperm motility and function and in
      development of a novel non-steroidal contraceptive for infertility.

PMID- 24918079
TI  - The Effects of Glyceryl Trinitrate Patch on the Treatment of Preterm Labor: A
      Single-blind Randomized Clinical Trial.
AB  - BACKGROUND: Preterm labor (PTL) is one of the main causes of neonatal mortality
      and morbidity. PTL leads to serious complications especially in the gestational
      age prior to 24-26 weeks. The aim of this study was to investigate the effect of
      glyceryl trinitrate (GTN) patch on the treatment and complications of PTL.
      METHODS: In this clinical trial, 84 singleton pregnant women with gestational age
      of 27-35 weeks were surveyed. PTL was clinically diagnosed and the patients were
      randomly divided into two groups who were treated with GTN or placebo for 48 hr.
      The consequences, complications and changes in some parameters in both groups
      were compared. Data were analyzed with chi square test, paired and unpaired t
      tests by SPSS software and p<0.05 was considered significant. RESULTS: No
      significant difference was observed between two groups in terms of successful
      tocolysis, receiving full dose of corticosteroids and the mean prolongation of
      the pregnancy. However, delivery times in patients who delivered during the
      hospitalization were 31+/-4.4 and 18.3+/-2.2 hr (p=0.01), respectively. Headache
      was more severe in control group (p=0.007). The systolic and mean arterial blood
      pressure decrease (p<0.001) and maternal heart rate increase (p=0.01) were
      significant in GTN group. The changes of vital signs were not significant in
      placebo group. CONCLUSION: The effect of GTN in the treatment of PTL is similar
      to the placebo without any serious complication. However, GTN delays the delivery
      time in delivery during the primary hospitalization. Thus, further studies with
      larger sample size are needed to evaluate the exact effects of GTN on PTL.

PMID- 24918080
TI  - Relationship between Structural and Intermediary Determinants of Health and
      Preterm Delivery.
AB  - BACKGROUND: Preterm birth is a major health problem that leads to infant
      morbidity and mortality. The main goal of this study was to find the relationship
      between social determinants of health and preterm delivery. METHODS: A
      prospective longitudinal cohort study was carried out on 500 pregnant women in
      their 24th to 28th gestational weeks in 2012. The pregnant women filled out a
      self-report questionnaire on the structural determinant, perceived stress, and
      perceived social support. The participants were followed up until labor and the
      data about mother and the newborn were collected after labor. The data were
      analyzed by SPSS 21 and Lisrel 8.8 software programs using pathway analysis.
      RESULTS: The final path model fit well (CFI=0.96; RMSEA=0.060). Path analysis
      showed that among structural factors, income had a direct effect (beta=0.06) and
      the factors of income (beta=0.00594), number of children (family size) (beta=
      0.024), as well as mother's education (beta=-0.0084) had the greatest overall
      effect on gestational age at birth respectively. Also, the results showed that
      among intermediate factors of social determinants of health, stress in the direct
      path (beta=-0.12) and among the overall effects, the perceived stress (beta=
      0.12) and perceived social support (beta=0.0396) affected the gestational age at
      birth. CONCLUSION: The current study showed that some structural and intermediary
      determinants such as income and perceived stress had an effect on preterm labor.

PMID- 24918081
TI  - Impairment of quality of life in symptomatic reproductive tract infection and
      sexually transmitted infection.
AB  - BACKGROUND: Reproductive tract infections (RTI) and sexually transmitted
      infections (STI) are often subclinical and remain undetected. The current study
      aimed to estimate the burden of RTI/STI, associated symptoms, risk factors and
      the impact of the condition on quality of life (QOL). METHODS: A community based,
      cross sectional study was conducted. Married women aged 18 to 49 years were
      selected through systematic random sampling in a rural area. A semi-structured
      questionnaire was used to evaluate socio-demographic characteristics, symptoms,
      risk factors and knowledge regarding RTI/STI. A standardized instrument from the
      World Health Organization (WHO-BREF) was used to measure QOL. The chi square
      (chi(2)) and unpaired t tests were used for statistic evaluation of results.
      RESULTS: In a sample of 464 women, 60 (13%) women were symptomatic and the
      commonest symptom was abnormal vaginal discharge (n = 54). 24 of the women had
      sought treatment. Age (p = 0.0006) and socio-economic status (p = 0.0004) were
      significant for an outcome of RTI/STI. Significant risk factors included lack of
      use of barrier contraceptives (p < 0.001), past history of infection (p < 0.001),
      use of reusable cloth during menstruation (p < 0.001) and presence of spousal
      symptoms (p < 0.001). QOL scores were impacted on all domains with significant
      differences. The largest mean difference was in the social relations and sexual
      activity domain. CONCLUSION: In the current study, the obtained data was a 13%
      prevalence of RTI/ STI symptoms with a significant lack of awareness regarding
      occurrence and prevention among women and significant impairment on all QOL
      domains.

PMID- 24918082
TI  - Sociodemographic factors associated with pap test adherence and cervical
      dysplasia in surgically sterilized women.
AB  - BACKGROUND: Routine dysplasia screening decreases the rates of cervical cancer.
      Since many women seek gynecological care to secure contraception, it was
      hypothesized that sterilized women will be less likely to undergo routine
      cervical cancer screening. Prior studies tried to evaluate this relationship, but
      results were conflicting. The study sought to further explore the
      sociodemographic and behavioral risk factors that might predispose sterilized
      women to be screening non-adherent and more likely to have cervical dysplasia.
      METHODS: Secondary analysis of women (n=1688) enrolled in a cross-sectional study
      in North America and divided into screening (n=925) and diagnostic (n=763) groups
      was performed. Information about sociodemographic and behavioral risk factors,
      surgical sterilization and date of last Pap test were obtained from
      questionnaires. Cervical histology was obtained from pathology records.
      Univariable analyses identified differences in risk factors between groups.
      Multivariable logistic regression models were constructed to evaluate Pap
      adherence and cervical dysplasia. RESULTS: Sterilized women were 39% more likely
      to be screening non-adherent (p<=0.05) especially if divorced, separated or
      widowed (OR=1.62), Hispanic (OR=1.57) and with a higher number of vaginal births
      (OR=2.00). Education was an effect measure modifier, significantly associated
      with non-adherence (OR=1.60). The association between sterilization and non
      adherence remained significant when adjusted for confounders (AOR=1.47).
      Sterilization was associated with an 80% increased odds of cervical dysplasia in
      women over 40. CONCLUSION: Sterilized women with certain sociodemographic factors
      are more likely to be non-adherent with Pap screening and more prone to
      dysplasia. These findings may assist practitioners in counseling at-risk
      patients.

PMID- 24918083
TI  - Outpatient follicle monitoring: a plea for standardization in ultrasound based
      follicle monitoring and data transfer.
AB  - BACKGROUND: The complexity of assisted reproductive technology (ART) increased
      during the last decades. New scientific and medical findings as well as the
      statutory requirements for improving the safety and the outcome of ART were the
      main impetus for its development. While therapy planning is done and ART is used
      by the IVF centers, the medical support and monitoring of patients is conducted
      by referring gynecologists. Reported follicle measurements by the gynecologist
      allow the adoption of the therapy plan. Most notably, the crucial aspect is
      processing and interpretation of ultrasound scan (US). The results of the
      received US, the transfer of data between IVF center(s) and referred physician(s)
      as well as the subjective interpretation often culminate in interpretation and
      logistical problems. This might increase the error probability with considerable
      detriments for the patients and ART outcome. METHODS: The follicle monitoring was
      performed using Voluson I ultrasound system combined with SonoAVC((r)) software.
      Results were communicated via DICOM language to DynaMed((r)) software, a medical
      program for managing an IVF center with seamless integration of all processes
      needed for an accurate and precise workflow. RESULTS: In this study, no loss of
      data was detected. All data were integrated by DynaMed((r)) software and were
      recallable in a fast and easy manner. CONCLUSION: The broad usage of Voluson I
      ultrasound SonoAVC((r)) software and communication of the results via Picture
      Archiving and Communication System (PACS) server between the IVF center and local
      gynecologist would provide more assistance for the patients and consequently the
      ART outcomes can be improved.

PMID- 24918084
TI  - The Case of Sacrococcygeal Teratoma in an IVF Pregnancy: Is There any Association
      between Congenital Tumors and Assisted Reproduction Techniques?
AB  - BACKGROUND: Sacrococcygeal teratoma (SCT) is a rare congenital tumor and its
      association with IVF pregnancy is not clear. There are limited reports of
      congenital tumors in IVF pregnancy. The exact embryogenesis of SCT is not known
      but a genetic etiology has been reported. Whether these congenital tumors have
      any association with assisted reproductive techniques remains obscure. CASE
      PRESENTATION: In this study, a case of SCT in an IVF pregnancy with donor oocytes
      was reported. IVF was performed for bilateral tubal blockade and poor ovarian
      reserve. It was diagnosed antenatally by ultrasonography. Successful surgical
      treatment was performed in postnatal period and six months follow-up remained
      uneventful. CONCLUSION: The purpose of reporting this case is to emphasize on the
      possibility of association of congenital tumors with assisted reproductive
      techniques and hence, the need for screening in these pregnancies. An association
      could not be detected based on few case reports and therefore, large population
      based studies are required to elucidate the effect of these reproductive
      techniques on occurrence of congenital tumors.

PMID- 24918085
TI  - A Novel de novo Balanced Reciprocal Translocation t(18;22) Associated with
      Recurrent Miscarriages: A Case Report.
AB  - BACKGROUND: Recurrent miscarriage is a major concern in the couples with
      reproductive problems. The chromosomal abnormalities, mainly balanced
      rearrangements are reported in variable phenotypes and the prevalence of them is
      2-8% in such couples. CASE PRESENTATION: In this study, the clinical, cytogenetic
      and molecular cytogenetic evaluations were performed on a couple with RM. The
      cytogenetic analysis of the husband revealed a balanced reciprocal translocation
      of t(18;22)(q21.1;q12) whereas wife had a normal karyotype of 46,XX. Further
      spectral karyotyping was performed to rule out the involvement of any other
      chromosomal aberrations present in the genome. Additional whole chromosome paint
      FISH (Fluorescence in situ hybridization) with paint probes 18 and 22 confirmed
      the translocation. CONCLUSION: To our knowledge, this is the first report of a
      novel (18;22) translocation with unique breakpoints and their association with
      RM. The reciprocal translocations provide a good opportunity for the
      identification of disease associated genes. However, in recurrent miscarriages,
      most of them do not disrupt any gene at the breakpoint but can lead to unbalanced
      gametes and hence poor reproductive outcome like RM or birth of a child with
      malformations and intellectual disability. The translocation breakpoints might be
      risk factors for RM. Moreover, the impact of the balanced translocations in
      association with RM is discussed in this report.

PMID- 24918086
TI  - Extramedullary acute myeloid leukemia: leukemic pleural effusion, case report and
      review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Malignant pleural effusions occur in the setting of
      both solid and hematologic malignancies. Pleural effusion caused by leukemic
      infiltration is an unusual extramedullary manifestation of acute myeloid leukemia
      (AML) with fewer than 20 cases reported (1-11). We report a case of pericardial
      and pleural effusions in a patient with AML and review the literature. CLINICAL
      PRESENTATION: In this case, a 55-year-old man with previous history of
      myeloproliferative neoplasm experienced transformation AML, heralded by
      appearance of leukemic pleural effusions. The patient was identified to have
      leukemic pleural effusion based on the extended cytogenetic analysis of the
      pleural fluid, as morphologic analysis alone was insufficient. INTERVENTION: The
      patient was treated with hypomethylator-based and intensive chemotherapy
      strategies, both of which maintained resolution of the effusions in the remission
      setting. CONCLUSION: Due to the rarity of diagnosis of leukemic pleural
      effusions, both cytogenetic and fluorescence in situ hybridization testing are
      recommended. Furthermore, systemic chemotherapy directed at the AML can lead to
      complete resolution of leukemic pleural effusions.

PMID- 24918087
TI  - O-GlcNAcylation: The Sweet Side of the Cancer.
AB  - O-GlcNAcylation is an O-linked beta-N-acetylglucosamine (O-GlcNAc) moiety linked
      to the serine or threonine residues in proteins. O-GlcNAcylation is a dynamic
      post-translational modification involved in a wide range of biological processes
      and diseases such as cancer. This modification can increase and decrease the
      activity of enzymes as well as interfere with protein stability and interaction.
      The modulatory capacity of O-GlcNAcylation, as well as protein phosphorylation,
      is of paramount importance in the regulation of metabolism and intracellular
      signaling of tumor cells. Thus, understanding the regulation of O-GlcNAcylation
      in tumor cells and their difference compared to non-tumor cells may elucidate new
      mechanisms related to tumor generation and development, could provide a new
      marker to diagnosis and prognosis in patients with cancer and indicate a new
      target to cancer chemotherapy. 

PMID- 24918088
TI  - Extracellular enolase of Candida albicans is involved in colonization of
      mammalian intestinal epithelium.
AB  - Enolase is secreted by Candida albicans and is present in its biofilms although
      its extracellular function is unknown. Here we show that extracellular enolase
      mediates the colonization of small intestine mucosa by C. albicans. Assays using
      intestinal mucosa disks show that C. albicans adhesion is inhibited, in a dose
      dependent mode, either by pretreatment of intestinal epithelium mucosa disks with
      recombinant C. albicans enolase (70% at 0.5 mg/ml enolase) or by pretreatment of
      C. albicans yeasts with anti-enolase antibodies (48% with 20 MUg antiserum). Also
      using flow cytometry, immunoblots of conditioned media and confocal microscopy we
      demonstrate that enolase is present in biofilms and that the extracellular
      enolase is not an artifact due to cell lysis, but must represent functional
      secretion of a stable form. This is the first direct evidence that C. albicans'
      extracellular enolase mediates colonization on its primary translocation site.
      Also, because enolase is encoded by a single locus in C. albicans, its dual role
      peptide, as glycolytic enzyme and extracellular peptide, is a remarkable example
      of gene sharing in fungi. 

PMID- 24918089
TI  - The importance of proteins of the RNase II/RNB-family in pathogenic bacteria.

PMID- 24918091
TI  - Lyme and associated tick-borne diseases: global challenges in the context of a
      public health threat.

PMID- 24918090
TI  - Influence of the tryptophan-indole-IFNgamma axis on human genital Chlamydia
      trachomatis infection: role of vaginal co-infections.
AB  - The natural history of genital Chlamydia trachomatis infections can vary widely;
      infections can spontaneously resolve but can also last from months to years,
      potentially progressing to cause significant pathology. The host and bacterial
      factors underlying this wide variation are not completely understood, but
      emphasize the bacterium's capacity to evade/adapt to the genital immune response,
      and/or exploit local environmental conditions to survive this immune response.
      IFNgamma is considered to be a primary host protective cytokine against
      endocervical C. trachomatis infections. IFNgamma acts by inducing the host enzyme
      indoleamine 2,3-dioxgenase, which catabolizes tryptophan, thereby depriving the
      bacterium of this essential amino acid. In vitro studies have revealed that
      tryptophan deprivation causes Chlamydia to enter a viable but non-infectious
      growth pattern that is termed a persistent growth form, characterized by a unique
      morphology and gene expression pattern. Provision of tryptophan can reactivate
      the bacterium to the normal developmental cycle. There is a significant
      difference in the capacity of ocular and genital C. trachomatis serovars to
      counter tryptophan deprivation. The latter uniquely encode a functional
      tryptophan synthase to synthesize tryptophan via indole salvage, should indole be
      available in the infection microenvironment. In vitro studies have confirmed the
      capacity of indole to mitigate the effects of IFNgamma; it has been suggested
      that a perturbed vaginal microbiome may provide a source of indole in vivo.
      Consistent with this hypothesis, the microbiome associated with bacterial
      vaginosis includes species that encode a tryptophanase to produce indole. In this
      review, we discuss the natural history of genital chlamydial infections,
      morphological and molecular changes imposed by IFNgamma on Chlamydia, and
      finally, the microenvironmental conditions associated with vaginal co-infections
      that can ameliorate the effects of IFNgamma on C. trachomatis. 

PMID- 24918092
TI  - Activities of three erythrocyte enzymes of hyperglycemic rats (Rattus norvegicus)
      treated with Allium sativa extract.
AB  - BACKGROUND: The present study sought to investigate erythrocyte glutathione S
      transferases (GST), NADH-Methaemoglobin reductase (NADH-MR) and Na(+)/K(+)-ATPase
      activities of hypoglycemic rats treated with ethanol/water (1:2 v/v) extract of
      A. sativa as agent of glycemic control. METHODS: Hyperglycemia was induced by a
      single intra-peritoneal injection of 0.1 mol/L alloxan monohydrate in phosphate
      buffer saline (PBS) solution (pH = 7.4); dosage = 140 mg/kg. At the end of the
      experimental time (t = 76 h), erythrocyte GST, NADH-MR and Na(+)/K(+)-ATPase
      activities as well as serum fasting blood sugar (FBS) levels were measured by
      spectrophotometric methods. RESULTS: Serum FBS levels of control/normal (C/N)
      rats ranged between 72.93 +/- 0.82-95.12 +/- 0.92 mg/dL, whereas experimental
      rats without glycemic control gave: 249.41 +/- 1.03-256.11 +/- 1.23 mg/dL.
      Hyperglycemic rats treated with ethanol/water (1:2 v/v) extract of A. sativa
      exhibited comparative reduced serum levels of FBS alongside with erythrocyte GST,
      NADH-MR and Na(+)/K(+)-ATPase activities. The average relative activities of the
      three enzymes and corresponding order of enzyme activity in hyperglycemic rats
      treated with ethanol/water (1:2 v/v) extract of A. sativa was: NADH-MR = 60.99% >
      GST = 47.81% > Na(+)/K(+)-ATPase = 46.81%. In the same order, relative activities
      of the three enzymes in rats without glycemic control were: NADH-MR = 49.65% >
      GST = 23.69% > Na(+)/K(+)-ATPase = 17.02%. CONCLUSION: Erythrocyte GST, NADH-MR
      and Na(+)/K(+)-ATPase activities gave insights into the pathophysiology of
      diabetic state and served as biomarkers for ascertaining therapeutic control in
      Type 1 diabetes mellitus.

PMID- 24918093
TI  - Oxidizability assay of unfractionated plasma of patients' with different plasma
      profile: a methodological study.
AB  - BACKGROUND: Present study describe the in vitro model of plasma oxidation of
      patients with different lipid profile, that can be correlated to their invivo
      plasma oxidizability in order to find the arterial diseases prone patient groups.
      METHOD: The method applied here to measure the invitro plasma oxidizability,
      accounts a convenient way that can be well suited in any clinical laboratory
      settings. Un-fractionated plasma was exposed to CuSO4 (5.0 mmol/L), a pro
      oxidant, and low frequency ultrasonic wave to induce oxidation, and finally
      oxidizability was calculated by TBARS and Conjugated Diene methods. RESULT: In
      our study, plasma LDL greater than 150 mg/dL possess 1.75 times more risk to
      undergo oxidation (CI, 0.7774 to 3.94; p = 0.071) than the low LDL plasma,
      percent of oxidation increased from 38.3% to 67.1% for the LDL level upto 150
      mg/dL and high. Lag phase, which is considered as the plasma antioxidative
      protection, was also influenced by the higher LDL concentration. The mean lag
      time was 65.27 +/- 20.02 (p = 0.02 compared to healthy), where as for 94.71 +/-
      35.11 min for the normolipidemic subject. The plasma oxidizability was also
      changed drastically for total cholesterol level, oxidative susceptibility shown
      35% and 55.02% for 200 mg/dL and high respectively, however it didn't appear as
      risk factor. Patient samples were also stratified according to their age, gender,
      and blood glucose level. Older persons (>=40 years) were 1.096 times (95% CL,
      0.5607 to 2.141, p = 0.396) than younger (<=39 years age), males are 1.071 (95%
      CI, 0.5072- 2.264) times than the females, and diabetic patients are 1.091 (CI,
      0.6153 to 1.934, p = 0.391) times in more risk than the non-diabetic counterpart.
      CONCLUSION: This method addressing its easy applicability in biomedical research.
      And by this we were able to show that patients with high LDL (>=150 mg/dL) are in
      alarming condition besides diabetic and elderly (>=40 years age) males are
      considered to be susceptible and more prone to develop vascular diseases.

PMID- 24918095
TI  - The prevalence of dyslipidemia in patients with diabetes mellitus of ayurveda
      Hospital.
AB  - BACKGROUND: Dyslipidemia is one of the major risk factors for cardiovascular
      disease in diabetes mellitus. Early detection and treatment of dyslipidemia in
      type-2 diabetes mellitus can prevent risk for atherogenic cardiovascular
      disorder. The rationale of this study was to detect the lipid abnormality in
      diabetic patients. METHODS: Necessary data was collected from the medical
      archives of 150 patients (73 female and 77 male) with diabetes mellitus
      registered in Department of pathology and biochemistry of a Ayurveda hospital
      established at Kolkata, India. RESULTS: The mean ages of female and male subjects
      were 51.8 +/- 10.8 and 53.2 +/- 11.3 years respectively. The range and mean value
      of FBS in females were 113-342 mg/dl and 157.7 +/- 6.3 mg/dl, while the range and
      mean value of PPBS in females were 135-560 mg/dl and 275.5 +/- 12.3 mg/dl
      respectively. Results showed that range and mean value of FBS in males were 111
      462 mg/dl and 160.8 +/- 7.4 mg/dl, while the range and mean value of PPBS in
      males were 136-598 mg/dl and 302.1 +/- 12.6 mg/dl respectively. Results of serum
      lipids showed that the mean values for total cholesterol (TC), triglyceride (TG),
      high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol
      (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) in female patients
      were 202.2 +/- 5.9 mg/dl, 168.3 +/- 8.2 mg/dl, 44.9 +/- 1.3 mg/dl, 123.6 +/- 5.2
      mg/dl and 33.7 +/- 1.7 mg/dl respectively. The mean values for TC, TG, HDL-C, LDL
      C and VLDL-C in male patients were 182.5 +/- 4.8 mg/dl, 128.1 +/- 10.8 mg/dl,
      40.8 +/- 1.2 mg/dl, 105.4 +/- 4.8 mg/dl and 36.2 +/- 2.2 respectively. FBS showed
      significant positive correlation with PPBS, cholesterol, TG, and VLDL-C. PPBS
      also demonstrated direct and significant correlations with TG and VLDL-C.
      CONCLUSIONS: The study showed common lipid abnormalities during diabetes induced
      dyslipidemia i.e., hypercholesterolemia, hypertriglyceridemia and elevated LDL-C.
      This study suggests the dominance of hyperlipidemia over increased prevalence of
      dyslipidemia.

PMID- 24918094
TI  - Insight into the impact of diabetes mellitus on the increased risk of
      hepatocellular carcinoma: mini-review.
AB  - Hepatocellular carcinoma is a multifactorial disease which is associated with a
      background of many causal risk factors. Diabetes mellitus however is one of the
      most common co-morbid illnesses found in hepatocellular carcinoma patients that
      are significantly associated with worsening of hepatocellular carcinoma
      development, patient prognosis and survival. Therefore, efforts have been focused
      on understanding the mechanisms underlying progression of hepatocellular
      carcinoma onset and development especially in diabetic patients. To our
      knowledge, there are no reports which address the impact of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) along with epigenetic regulations
      associated with increased risk of hepatocellular carcinoma confounded by diabetes
      mellitus. Therefore, this mini-review focuses on the possible intermediary
      mechanisms involved in worsening the onset and progression of hepatocellular
      carcinoma development confounded by diabetes mellitus. The first approach is to
      look at the role of inflammatory mediators (TNF-alpha and IL-6) in apoptosis and
      inflammation during hepatocarcinogenesis through monitoring levels of apoptotic
      regulators, B-cell lymphoma 2 protein which is encoded by BCL2 gene and apoptosis
      regulator BAX known as bcl-2-like protein 4 which is encoded by the BAX gene. The
      second approach is to focus on the possible epigenomic reprogramming that drives
      hepatocellular transformation since epigenetic modification of DNA is a key
      feature in the pathogenesis of hepatocarcinogenesis. Both approaches may suggest
      role of using Bcl2 and Bax as apoptotic and inflammatory markers for
      hepatocellular carcinoma detection as well as the importance impact of DNA
      methylation, hypomethylation or histone modifications as attractive candidates
      for early-detection biomarkers of hepatocellular carcinoma. 

PMID- 24918096
TI  - Minimally invasive surgery for pediatric tumors - current state of the art.
AB  - During recent years, minimally invasive surgery (MIS) has become the standard
      approach for various operations in infants and children. This also holds true for
      surgery in children with solid tumors. Meanwhile, more and more oncological
      biopsies and resections are being performed laparoscopically or
      thoracoscopically. Despite its increasing role in pediatric tumor surgery, the
      different national and international multicenter trial groups have not yet
      implemented MIS within guidelines and recommendations in most of the current
      treatment protocols. An increasing number of reports describe a potential role of
      MIS in the different entities of pediatric surgical oncology. Over the time,
      there has been a diverse development of this approach with regard to the
      different neoplasms. The aim of this article is to give an overview and to
      describe the current state of the art of MIS in pediatric solid tumors. 

PMID- 24918097
TI  - My tribute to Mary ellen avery.

PMID- 24918098
TI  - Repeated insulin-like growth factor 1 treatment in a patient with rett syndrome:
      a single case study.
AB  - Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no
      cure. Patients show regression of acquired skills, motor, and speech impairment,
      cardio-respiratory distress, microcephaly, and stereotyped hand movements. The
      majority of RTT patients display mutations in the gene that codes for the Methyl
      CpG binding protein 2 (MeCP2), which is involved in the development of the
      central nervous system, especially synaptic and circuit maturation. Thus, agents
      that promote brain development and synaptic function are good candidates for
      ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1
      (IGF1) and its active peptide (1-3) IGF1 cross the Blood Brain Barrier, and
      therefore are ideal treatments for RTT Indeed, both (1-3) IGF1 and IGF1 treatment
      significantly ameliorates RTT symptoms in a mouse model of the disease In a
      previous study, we established that IGF1 is safe and well tolerated on Rett
      patients. In this open label clinical case study, we assess the safety and
      tolerability of IGF1 administration in two cycles of the treatment. Before and
      after each cycle, we monitored the clinical and blood parameters, autonomic
      function, and social and cognitive abilities, and we found that IGF1 was well
      tolerated each time and did not induce any side effect, nor it interfered with
      the other treatments that the patient was undergoing. We noticed a moderate
      improvement in the cognitive, social, and autonomic abilities of the patient
      after each cycle but the benefits were not retained between the two cycles,
      consistent with the pre-clinical observation that treatments for RTT should be
      administered through life. We find that repeated IGF1 treatment is safe and well
      tolerated in Rett patients but observed effects are not retained between cycles.
      These results have applications to other pathologies considering that IGF1 has
      been shown to be effective in other disorders of the autism spectrum. 

PMID- 24918100
TI  - Does groundwater protection in Europe require new EU-wide environmental quality
      standards?
AB  - The European Groundwater Directive could be improved by limiting the scopes of
      the Annexes I and II to the manmade and natural substances, respectively, and by
      defining a common monitoring protocol. The changes in the European landuse
      patterns, in particular the urban sprawl phenomena, obscure the distinction
      between the point and diffuse sources of contamination. In the future more
      importance will be given to the household contamination. Moreover, the
      agricultural environment could be used for developing new conceptual models
      related to the pharmaceuticals. 

PMID- 24918099
TI  - Breakfast: to skip or not to skip?

PMID- 24918101
TI  - Unusual truncation of N-acylated peptoids under acidic conditions.
AB  - The terminal amino groups of peptoids have often been protected with acetyl
      groups to improve cell permeability and therapeutic potential, and to prevent the
      poisoning of the catalysts in organometallic reactions. Interestingly, the
      unusual truncation of the terminal peptoid unit has sometimes been encountered
      when the acetylated linear peptoids were treated with a TFA cleavage cocktail. In
      this study, we systematically investigated the electronic effects of acyl groups
      on the truncation of N-acylated peptoids to rationalize the formation of the
      deleted peptoids and to establish an appropriate strategy for preventing such
      undesired truncation. 

PMID- 24918102
TI  - The selective electrochemical detection of homocysteine in the presence of
      glutathione, cysteine, and ascorbic acid using carbon electrodes.
AB  - The detection of homocysteine, HCys, was achieved with the use of catechol via
      1,4-Michael addition reaction using carbon electrodes: a glassy carbon electrode
      and a carbon nanotube modified glassy carbon electrode. The selective detection
      of homocysteine was investigated and achieved in the absence and presence of
      glutathione, cysteine and ascorbic acid using cyclic voltammetry and square wave
      voltammetry. A calibration curve of homocysteine detection was determined and the
      sensitivity is (0.20 +/- 0.02) MUA MUM(-1) and the limit of detection is 660 nM
      within the linear range. Lastly, commercially available multi walled carbon
      nanotube screen printed electrodes were applied to the system for selective
      homocysteine detection. This work presents a potential practical application
      towards medical applications as it can be highly beneficial towards quality
      healthcare management. 

PMID- 24918103
TI  - Combined use of quantitative ED-EPMA, Raman microspectrometry, and ATR-FTIR
      imaging techniques for the analysis of individual particles.
AB  - In this work, quantitative energy-dispersive electron probe X-ray microanalysis
      (ED-EPMA) (called low-Z particle EPMA), Raman microspectrometry (RMS), and
      attenuated total reflectance Fourier transform infrared spectroscopic (ATR-FTIR)
      imaging were applied in combination for the analysis of the same individual
      airborne particles for the first time. After examining individual particles of
      micrometer size by low-Z particle EPMA, consecutive examinations by RMS and ATR
      FTIR imaging of the same individual particles were then performed. The relocation
      of the same particles on Al or Ag foils was successfully carried out among the
      three standalone instruments for several standard samples and an indoor airborne
      particle sample, resulting in the successful acquisition of quality spectral data
      from the three single-particle analytical techniques. The combined application of
      the three techniques to several different standard particles confirmed that those
      techniques provided consistent and complementary chemical composition information
      on the same individual particles. Further, it was clearly demonstrated that the
      three different types of spectral and imaging data from the same individual
      particles in an indoor aerosol sample provided richer information on
      physicochemical characteristics of the particle ensemble than that obtainable by
      the combined use of two single-particle analytical techniques. 

PMID- 24918104
TI  - n-Bu4NI/TBHP-catalyzed direct amination of allylic and benzylic C(sp3)-H with
      anilines under metal-free conditions.
AB  - A novel and efficient n-Bu4NI/TBHP-catalyzed direct amination of allylic and
      benzylic C(sp(3))-H with anilines to form N-substituted anilines under metal-free
      conditions has been developed. 

PMID- 24918105
TI  - A photothermal cell viability-reporting theranostic nanoprobe for intraoperative
      optical ablation and tracking of tumors.
AB  - A photothermal pH-reporting nanoprobe was developed for intraoperative tumor
      detection by "turn-on" fluorescence of the probe inside viable tumor cells,
      photothermal tumor therapy, and in situ monitoring of tumor killing by non
      fluorescence of the probe in damaged cells. 

PMID- 24918106
TI  - NH3 treatment of TiO2 nanotubes: from N-doping to semimetallic conductivity.
AB  - In the present work we show that a suitable high temperature ammonia treatment
      allows for the conversion of single-walled TiO2 nanotube arrays not only to a N
      doped photoactive anatase material (which is already well established), but even
      further into fully functional titanium nitride (TiN) tubular structures that
      exhibit semimetallic conductivity. 

PMID- 24918107
TI  - Copper-catalyzed Hiyama cross-coupling using vinylsilanes and benzylic
      electrophiles.
AB  - Allylbenzene derivatives are ubiquitous frameworks in organic chemistry. Herein
      is described an efficient copper-catalyzed cross-coupling reaction using
      vinylsilanes and benzyl bromides, leading to the synthesis of allylbenzenes. This
      methodology allows the use of cis, trans and 1,1'-disubstituted vinylsilanes as
      well as a large number of sensitive moieties. 

PMID- 24918108
TI  - Semi-artificial and bioactive ferroxidase with nanoparticles as the active sites.
AB  - Light-chain apoferritin lacks ferroxidase activity, which can be supplemented
      with Pt-nanoparticles. The hybrid bioinorganic nanoparticle outperforms its heavy
      chain pendant in terms of ferroxidase activity, mineralization ability and
      inhibition resistance. Being active in a cellular environment it regulates the
      iron homeostasis. 

PMID- 24918109
TI  - A large-scale quantitative analysis of latent factors and sentiment in online
      doctor reviews.
AB  - Online physician reviews are a massive and potentially rich source of information
      capturing patient sentiment regarding healthcare. We analyze a corpus comprising
      nearly 60,000 such reviews with a state-of-the-art probabilistic model of text.
      We describe a probabilistic generative model that captures latent sentiment
      across aspects of care (eg, interpersonal manner). We target specific aspects by
      leveraging a small set of manually annotated reviews. We perform regression
      analysis to assess whether model output improves correlation with state-level
      measures of healthcare. We report both qualitative and quantitative results.
      Model output correlates with state-level measures of quality healthcare,
      including patient likelihood of visiting their primary care physician within 14
      days of discharge (p=0.03), and using the proposed model better predicts this
      outcome (p=0.10). We find similar results for healthcare expenditure. Generative
      models of text can recover important information from online physician reviews,
      facilitating large-scale analyses of such reviews.

PMID- 24918110
TI  - Synthesis of isochromene-type scaffolds via single-flask Diels-Alder-[4 + 2]
      annulation sequence of a silyl-substituted diene with menadione.
AB  - A sequential Diels-Alder reaction/silicon-directed [4 + 2]-annulation was
      developed to assemble hydroisochromene-type ring systems from menadione 2. In the
      first step, a Diels-Alder of the 1-silyl-substituted butadiene 1 with 2 furnished
      an intermediate cyclic allylsilane. Subsequently, TMSOTf promoted a [4 + 2]
      annulation through trapping of an oxonium, generated by condensation between an
      aldehyde and the TBS protected alcohol resulted in the formation of a cis-fused
      hydroisochromene 13. 

PMID- 24918111
TI  - Estimating influence of cofragmentation on peptide quantification and
      identification in iTRAQ experiments by simulating multiplexed spectra.
AB  - Isobaric tag-based quantification such as iTRAQ and TMT is a promising approach
      to mass spectrometry-based quantification in proteomics as it provides wide
      proteome coverage with greatly increased experimental throughput. However, it is
      known to suffer from inaccurate quantification and identification of a target
      peptide due to cofragmentation of multiple peptides, which likely leads to under
      estimation of differentially expressed peptides (DEPs). A simple method of
      filtering out cofragmented spectra with less than 100% precursor isolation purity
      (PIP) would decrease the coverage of iTRAQ/TMT experiments. In order to estimate
      the impact of cofragmentation on quantification and identification of iTRAQ
      labeled peptide samples, we generated multiplexed spectra with varying degrees of
      PIP by mixing the two MS/MS spectra of 100% PIP obtained in global proteome
      profiling experiments on gastric tumor-normal tissue pair proteomes labeled by 4
      plex iTRAQ. Despite cofragmentation, the simulation experiments showed that more
      than 99% of multiplexed spectra with PIP greater than 80% were correctly
      identified by three different database search engines-MODa, MS-GF+, and Proteome
      Discoverer. Using the multiplexed spectra that have been correctly identified, we
      estimated the effect of cofragmentation on peptide quantification. In 74% of the
      multiplexed spectra, however, the cancer-to-normal expression ratio was
      compressed, and a fair number of spectra showed the "ratio inflation" phenomenon.
      On the basis of the estimated distribution of distortions on quantification, we
      were able to calculate cutoff values for DEP detection from cofragmented spectra,
      which were corrected according to a specific PIP and probability of type I (or
      type II) error. When we applied these corrected cutoff values to real
      cofragmented spectra with PIP larger than or equal to 70%, we were able to
      identify reliable DEPs by removing about 25% of DEPs, which are highly likely to
      be false positives. Our experimental results provide useful insight into the
      effect of cofragmentation on isobaric tag-based quantification methods. The
      simulation procedure as well as the corrected cutoff calculation method could be
      adopted for quantifying the effect of cofragmentation and reducing false
      positives (or false negatives) in the DEP identification with general
      quantification experiments based on isobaric labeling techniques. 

PMID- 24918112
TI  - Voluntary enhanced cocontraction of hamstring muscles during open kinetic chain
      leg extension exercise: its potential unloading effect on the anterior cruciate
      ligament.
AB  - BACKGROUND: A number of research studies provide evidence that hamstring
      cocontraction during open kinetic chain knee extension exercises enhances
      tibiofemoral (TF) stability and reduces the strain on the anterior cruciate
      ligament. PURPOSE: To determine the possible increase in hamstring muscle
      coactivation caused by a voluntary cocontraction effort during open kinetic chain
      leg-extension exercises, and to assess whether an intentional hamstring
      cocontraction can completely suppress the anterior TF shear force during these
      exercises. STUDY DESIGN: Descriptive laboratory study. METHODS: Knee kinematics
      as well as electromyographic activity in the semitendinosus (ST), semimembranosus
      (SM), biceps femoris (BF), and quadriceps femoris muscles were measured in 20
      healthy men during isotonic leg extension exercises with resistance (R) ranging
      from 10% to 80% of the 1-repetition maximum (1RM). The same exercises were also
      performed while the participants attempted to enhance hamstring coactivation
      through a voluntary cocontraction effort. The data served as input parameters for
      a model to calculate the shear and compressive TF forces in leg extension
      exercises for any set of coactivation patterns of the different hamstring
      muscles. RESULTS: For R<= 40% 1RM, the peak coactivation levels obtained with
      intentional cocontraction (l) were significantly higher (P < 10(-3)) than those
      obtained without intentional cocontraction (l 0). For each hamstring muscle,
      maximum level l was reached at R = 30% 1RM, corresponding to 9.2%, 10.5%, and
      24.5% maximum voluntary isometric contraction (MVIC) for the BF, ST, and SM,
      respectively, whereas the ratio l/l 0 reached its maximum at R = 20% 1RM and was
      approximately 2, 3, and 4 for the BF, SM, and ST, respectively. The voluntary
      enhanced coactivation level l obtained for R<= 30% 1RM completely suppressed the
      anterior TF shear force developed by the quadriceps during the exercise.
      CONCLUSION: In leg extension exercises with resistance R<= 40% 1RM, coactivation
      of the BF, SM, and ST can be significantly enhanced (up to 2, 3, and 4 times,
      respectively) by a voluntary hamstring cocontraction effort. The enhanced
      coactivation levels obtained for R<= 30% 1RM can completely suppress the anterior
      TF shear force developed by the quadriceps during the exercise. CLINICAL
      RELEVANCE: This laboratory study suggests that leg extension exercise with
      intentional hamstring cocontraction may have the potential to be a safe and
      effective quadriceps-strengthening intervention in the early stages of
      rehabilitation programs for anterior cruciate ligament injury or reconstruction
      recovery. Further studies, including clinical trials, are needed to investigate
      the relevance of this therapeutic exercise in clinical practice.

PMID- 24918114
TI  - Prosthetic hip joint infection caused by non-capsulated Haemophilus influenzae.
AB  - Haemophilus influenzae is rarely described as a causative agent of prosthetic
      joint infections. Here, a case of prosthetic hip joint infection caused by H.
      influenzae is reported. Treatment was successful, resulting in implant salvage,
      by debridement and antibiotic treatment with ciprofloxacin as monotherapy for 3
      months.

PMID- 24918113
TI  - Synthesis of site-specific DNA-protein conjugates and their effects on DNA
      replication.
AB  - DNA-protein cross-links (DPCs) are bulky, helix-distorting DNA lesions that form
      in the genome upon exposure to common antitumor drugs, environmental/occupational
      toxins, ionizing radiation, and endogenous free-radical-generating systems. As a
      result of their considerable size and their pronounced effects on DNA-protein
      interactions, DPCs can interfere with DNA replication, transcription, and repair,
      potentially leading to mutagenesis, genotoxicity, and cytotoxicity. However, the
      biological consequences of these ubiquitous lesions are not fully understood due
      to the difficulty of generating DNA substrates containing structurally defined,
      site-specific DPCs. In the present study, site-specific cross-links between the
      two biomolecules were generated by copper-catalyzed [3 + 2] Huisgen cycloaddition
      (click reaction) between an alkyne group from 5-(octa-1,7-diynyl)-uracil in DNA
      and an azide group within engineered proteins/polypeptides. The resulting DPC
      substrates were subjected to in vitro primer extension in the presence of human
      lesion bypass DNA polymerases eta, kappa, nu, and iota. We found that DPC lesions
      to the green fluorescent protein and a 23-mer peptide completely blocked DNA
      replication, while the cross-link to a 10-mer peptide was bypassed. These results
      indicate that the polymerases cannot read through the larger DPC lesions and
      further suggest that proteolytic degradation may be required to remove the
      replication block imposed by bulky DPC adducts. 

PMID- 24918115
TI  - Risk factors for the acquisition of imipenem-resistant Acinetobacter baumannii in
      a burn unit: An appraisal of the effect of colonization pressure.
AB  - Imipenem-resistant Acinetobacter baumannii (IRAB) is a major threat for
      critically ill patients, including those admitted to burn units. Recent studies
      have suggested that colonization pressure (the proportion of patients or patient
      days harbouring the pathogen of interest) is an important driver of the risk for
      acquisition of multidrug-resistant organisms. With that in mind, we conducted a
      cohort study, enrolling 208 patients admitted to a burn unit from November 2008
      through December 2009. The outcome of interest was the acquisition of IRAB. In
      addition to the usual risk factors, we assessed the impact of colonization
      pressure. The number of wound excisions (odds ratio (OR) 12.06, 95% confidence
      interval (CI) 2.82-51.64) and the number of antimicrobials used (OR 22.82, 95% CI
      5.15-101.19) were significant risk factors for the outcome of interest. On the
      other hand, colonization pressure (measured for whole time of exposure or up to
      the last 14, 7, or 3 days) was not associated with the risk for IRAB acquisition.

PMID- 24918116
TI  - Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus
      free world?
AB  - About 2% of the world's population is estimated to be chronically infected with
      hepatitis C virus (HCV). These chronic carriers are at risk of developing liver
      cirrhosis and its complications. Successful treatment of HCV infection is
      associated with improved quality of life and increased survival. Antiviral
      approaches were formerly based on interferon and therefore all patients with a
      contraindication to interferon were excluded from treatment (e.g., patients with
      decompensated disease, severe impairment of other organs). Very recently,
      interferon-free combinations have become available for genotypes 2 and 3. This
      review focuses on the most recently reported data on the various interferon-free
      combinations used (namely, sofosbuvir-based combinations, the ABT
      450/ombitasvir/dasabuvir/ribavirin combination, the daclatasvir/asunaprevir
      combination, and the MK-5172/MK-8742 combination). All these combinations yielded
      amazing results in terms of efficacy (90-100%), tolerability and safety. If the
      problem of the high cost is overcome, interferon-free therapies will lead to what
      has long been a chimera, namely, an HCV-free world. 

PMID- 24918117
TI  - Epidemiology and management of Buruli ulcer.
AB  - Buruli ulcer (Mycobacterium ulcerans infection) is a neglected tropical disease
      of skin and subcutaneous tissue that can result in long-term cosmetic and
      functional disability. It is a geographically restricted infection but
      transmission has been reported in endemic areas in more than 30 countries
      worldwide. The heaviest burden of disease lies in West and Sub-Saharan Africa
      where it affects children and adults in subsistence agricultural communities.
      Mycobacterium ulcerans infection is probably acquired via inoculation of the skin
      either directly from the environment or indirectly via insect bites. The
      environmental reservoir and exact route of transmission are not completely
      understood. It may be that the mode of acquisition varies in different parts of
      the world. Because of this uncertainty it has been nicknamed the 'mysterious
      disease'. The therapeutic approach has evolved in the past decade from aggressive
      surgical resection alone, to a greater focus on antibiotic therapy combined with
      adjunctive surgery. 

PMID- 24918119
TI  - Omics profiles in chronic venous ulcer wound fluid: innovative applications for
      translational medicine.
AB  - Chronic venous disease represents a healthcare problem due to high prevalence and
      recurrence rates. Studies on chronic venous ulcer wound fluid (CVUWF) have
      demonstrated increased inflammation and proteolysis which can cause tissue
      destruction and delayed healing. This review discusses: nearly all known
      metabolites discovered in the past 25 years in CVUWF studies; the omics
      approaches characterizing the microenvironment of human venous leg ulcers; and
      the use of biocompounds as prognostic biomarkers and as possible targets for
      therapeutic approaches. A biomarker is a biological compound that can be
      functional or non-functional, specific or non-specific in the diagnosis/prognosis
      to a disease state and may be quantified to determine progression or regression
      of disease. Omics studies in CVUWF provide the impetus for future identification
      of biomarkers within the intricate network in chronic venous disease and set the
      basis for determining the appropriate combination of molecules that are expressed
      with the healing status of venous leg ulcers. 

PMID- 24918118
TI  - Plant responses to bacterial N-acyl L-homoserine lactones are dependent on
      enzymatic degradation to L-homoserine.
AB  - Many bacteria use quorum sensing (QS) to regulate phenotypes that ultimately
      benefit the bacterial population at high cell densities. These QS-dependent
      phenotypes are diverse and can have significant impacts on the bacterial host,
      including virulence factor production, motility, biofilm formation,
      bioluminescence, and root nodulation. As bacteria and their eukaryotic hosts have
      coevolved over millions of years, it is not surprising that certain hosts appear
      to be able to sense QS signals, potentially allowing them to alter QS outcomes.
      Recent experiments have established that eukaryotes have marked responses to the
      N-acyl L-homoserine lactone (AHL) signals used by Gram-negative bacteria for QS,
      and the responses of plants to AHLs have received considerable scrutiny to date.
      However, the molecular mechanisms by which plants, and eukaryotes in general,
      sense bacterial AHLs remain unclear. Herein, we report a systematic analysis of
      the responses of the model plants Arabidopsis thaliana and Medicago truncatula to
      a series of native AHLs and byproducts thereof. Our results establish that AHLs
      can significantly alter seedling growth in an acyl-chain length dependent manner.
      Based upon A. thaliana knockout studies and in vitro biochemical assays, we
      conclude that the observed growth effects are dependent upon AHL amidolysis by a
      plant-derived fatty acid amide hydrolase (FAAH) to yield L-homoserine. The
      accumulation of l-homoserine appears to encourage plant growth at low
      concentrations by stimulating transpiration, while higher concentrations inhibit
      growth by stimulating ethylene production. These results offer new insights into
      the mechanisms by which plant hosts can respond to QS signals and the potential
      role of QS in interkingdom associations.

PMID- 24918120
TI  - Global differences between women and men in the prevalence of obesity: is there
      an association with gender inequality?
AB  - BACKGROUND/OBJECTIVES: In most populations the prevalence of obesity is greater
      in women than in men; however, the magnitude of the difference between the sexes
      varies significantly by country. We considered the role of gender inequality in
      explaining these disparities. SUBJECTS/METHODS: We undertook an ecological
      analysis of internationally comparable obesity prevalence data to examine the
      association between indicators of gender inequality and the differences between
      men and women in obesity prevalence. Gender inequality was assessed using three
      measures: the Gender Inequality Index, the Global Gender Gap Index and the Social
      Institutions and Gender Index. We fitted multiple regression models to examine
      the association. RESULTS: We found that the prevalence of obesity across
      countries shows gendered patterning with greater prevalence and greater
      heterogeneity in women than in men (P<0.001). We also found that two of three
      measures of gender inequality were significantly associated with the sex
      differences in obesity prevalence across countries. CONCLUSIONS: The patterning
      of obesity across countries is gendered. However, the association between global
      measures of gender inequality and the sex gap in obesity is dependent on the
      measure used. Further research is needed to investigate the mechanisms that
      underpin the gendered nature of obesity prevalence.

PMID- 24918121
TI  - Association between PON1 rs662 polymorphism and coronary artery disease.
AB  - BACKGROUND/OBJECTIVES: Paraoxonase 1 (PON1) is a plasma enzyme that is capable of
      inhibiting the progression of atherosclerosis, and is associated with
      susceptibility of coronary artery disease (CAD). PON protein expression is
      present in human aortic tissue and it plays an important role in the progression
      of atherosclerosis. This study aimed to investigate PON1 immunohistochemistry in
      human coronary arteries, determine its polymorphisms and plasma status, and
      analyze its association with the risk of CAD. SUBJECTS/METHODS: PON1 expression
      in human coronary artery tissues was detected by immunohistochemical staining.
      PON1 polymorphisms were determined by polymerase chain reaction direct sequencing
      in 2456 unrelated Chinese Han individuals. Serum PON1 levels were indirectly
      reflected by PON1 activity towards paraoxon and phenylacetate by
      spectrophotometry, and by its concentrations using a human enzyme-linked
      immunosorbent assay. RESULTS: Immunohistochemical analysis showed that PON1
      expression was lower in atherosclerotic arteries than in normal arteries. PON1
      Q192R (rs662) had a significant effect on the risk of CAD (P=0.001). In a
      logistic regression model, after adjusting for conventional risk factors of CAD,
      192R allele carriers had a significantly higher risk of CAD than other allele
      carriers. Serum PON1 activity and concentrations were significantly reduced in
      CAD patients compared with controls (P<0.05), and highly associated with the R
      allele. CONCLUSIONS: Low PON1 expression in human atherosclerotic coronary
      arteries is associated with CAD. Moreover, PON1 Q192R polymorphism is
      significantly associated with susceptibility of CAD in the Chinese Han
      population, and the 192R allele might be an independent predictor for CAD.

PMID- 24918122
TI  - Consumer attitudes and understanding of cholesterol-lowering claims on food:
      randomize mock-package experiments with plant sterol and oat fibre claims.
AB  - BACKGROUND/OBJECTIVES: Few studies have examined consumer acceptability or
      comprehension of cholesterol-lowering claims on food labels. Our objective was to
      assess consumer attitudes and understanding of cholesterol-lowering claims
      regarding plant sterols (PS) and oat fibre (OF). SUBJECTS/METHODS: We conducted
      two studies on: (1) PS claims and (2) OF claims. Both studies involved a
      randomized mock-packaged experiment within an online survey administered to
      Canadian consumers. In the PS study (n=721), we tested three PS-related claims
      (disease risk reduction claim, function claim and nutrient content claim) and a
      'tastes great' claim (control) on identical margarine containers. Similarly, in
      the OF study (n=710), we tested three claims related to OF and a 'taste great'
      claim on identical cereal boxes. In both studies, participants answered the same
      set of questions on attitudes and understanding of claims after seeing each mock
      package. RESULTS: All claims that mentioned either PS or OF resulted in more
      positive attitudes than the taste control claim (P<0.0001), despite all products
      within each study having the same nutrition profile. How consumers responded to
      the nutrition claims between the two studies was influenced by contextual factors
      such as familiarity with the functional food/component and the food product that
      carried the claim. CONCLUSIONS: Permitted nutrition claims are approved based on
      physiological evidence and are allowed on any food product as long as it meets
      the associated nutrient criteria. However, it is difficult to generalize
      attitudes and understanding of claims when they are so highly dependent on
      contextual factors.

PMID- 24918124
TI  - Management of cystic diseases of the pancreas.
AB  - Pancreatic cysts are challenging to the gastroenterologist. Detection rate is
      increasing and neither criteria for a definitive diagnosis, nor a validated
      surveillance strategy is available. Pancreatic endosonography with or without
      sampling is necessary in most of the cases. However this technique requires
      expertise and is not widely available. While some cysts have a malignant
      potential or already malign at the diagnosis, most are benign and remain so for
      decades. We are going to review the existing data on this controversial subject. 

PMID- 24918125
TI  - Accuracy of biopsies for Helicobacter pylori in the presence of intestinal
      metaplasia of the stomach.
AB  - BACKGROUND/AIMS: Gastric cancer is the second leading cause of cancer-related
      death worldwide. The majority of gastric cancers is "intestinal-type"
      adenocarcinoma, caused in part by H. pylori infection. Chronic gastritis leading
      to atrophy and intestinal metaplasia (IM) can result in cancer. Studies have
      demonstrated reversibility of mucosal atrophy following H. pylori eradication.
      Concern has been raised regarding the sensitivity of gastric biopsy for H. pylori
      detection in the context of IM. MATERIALS AND METHODS: All cases of IM on gastric
      biopsy from a single gastroenterologist's outpatient practice were
      retrospectively reviewed from February 1, 2006 until May 31, 2012. RESULTS: In
      total, 105 IM cases were found, of which 37 (35.2%, 95% CI: 26.3-45.2) were H.
      pylori-positive on biopsy. Charts of the remaining 68 patients were reviewed for
      availability of other tests, namely urea breath test (UBT) and serology. Of 43 H.
      pylori-negative patients who underwent a UBT, 10 were positive for the infection
      (23.3%, 95% CI: 12.3-39.0). Amongst patients with coexisting autoimmune gastritis
      (AIG), 4 out of 9 (44.4%, 95% CI: 15.3-77.3) also had evidence of H. pylori
      infection by UBT, despite negative histology. CONCLUSION: For cases of gastric IM
      with negative histology for H. pylori, UBT should be considered, even in cases of
      AIG, as this may alter the management and clinical course for patients.

PMID- 24918123
TI  - Is low docosahexaenoic acid associated with disturbed rhythms and
      neurodevelopment in offsprings of diabetic mothers?
AB  - BACKGROUND/OBJECTIVE: To evaluate the relation between docosahexaenoic acid (DHA)
      status and neurodevelopment in the offsprings of gestational diabetic mothers
      (ODMs). SUBJECTS/METHODS: A prospective cohort study was performed. The offspring
      of 63 pregnant women (23 controls, 21 diet-controlled gestational diabetes
      mellitus (GDM) and 19 insulin-treated GDM) were recruited. Maternal and venous
      cord plasma DHA percentages were analyzed. Skin temperature and activity in
      children were recorded for 72 h at 3 and 6 months of life. Neurodevelopment was
      assessed using the Bayley Scale of Infant Development II (BSID II) at 6 and 12
      months of age. RESULTS: Cord plasma DHA percentage was significantly lower in the
      ODMs compared with that in the controls (Control 6.43 [5.04-7.82](a); GDM+diet
      5.65 [4.44-6.86](ab); GDM+insulin 5.53 [4.45-6.61](b)). Both mental (Control
      102.71 [97.61-107.81](a); GDM+diet 100.39 [91.43-109.35](a); GDM+insulin 93.94
      [88.31-99.57](b)) and psychomotor (Control 91.52 [81.82-101.22](a); GDM+diet
      81.67 [73.95-89.39](b); GDM+insulin 81.89 [71.96-91.85](b)) scores evaluated by
      the BSID II were significantly lower at 6 months in ODMs, even after adjusting
      for confounding factors such as breastfeeding, maternal educational level and
      gender. Cord plasma DHA percentage correlated with the psychomotor score from
      BSID II (r=0.27; P=0.049) and with the intra-daily variability in activity (r=
      0.24; P=0.043) at 6 months. Maternal DHA was correlated with several sleep rhythm
      maturation parameters at 6 months. CONCLUSIONS: Lower DHA levels in cord plasma
      of ODMs could affect their neurodevelopment. Maternal DHA status was also
      associated with higher values in the sleep rhythm maturation parameters of
      children.

PMID- 24918126
TI  - Comparison of the clinicopathological features of flat and polypoid colorectal
      adenomas that are smaller than or equal to five millimeters.
AB  - BACKGROUND/AIMS: Colorectal flat adenomas (FAs) may represent a different
      histogenesis, since their malignant potential is thought to be higher than
      polypoid adenomas of the same size. In this study, we classified FAs of <=5 mm
      into three subgroups-superficially elevated adenomas (SEAs), completely flat
      adenomas (CFAs), and depressed adenomas (DAs)-based on their low microscopic
      shapes and compared their clinicopathological features with polypoid tubular
      adenomas (pTAs) with the same size. MATERIALS AND METHODS: One hundred one pTAs
      and 46 FAs with tubular morphology with the same size (<=5 mm) were studied.
      RESULTS: The percentages of high-grade dysplasia in FAs and pTAs were 19.56% and
      12.87%, respectively. The percentages of the high-grade dysplasia were 28.57%,
      13.63%, and 20.00% in the DA, SEA, and CFA subgroups, respectively. FAs had a
      significantly higher number of normal epithelium at the basal crypts of the
      lesion than the pTAs (p=0.001). The presence of pericryptal mesenchymal cells was
      higher in pTAs than the FAs (78.21% vs 10.86%) (p<0.001). CONCLUSION: Flat
      adenoma represents a distinct type of colorectal adenoma with special
      histopathological properties-existence of a normal epithelium at the basal
      crypts, lack of pericryptal mesenchymal cells, and a high percentage of high
      grade dysplasia-especially when it has a depressed shape at low magnification.

PMID- 24918127
TI  - Serrated lesions of the appendix: do they differ from their colorectal
      counterparts?
AB  - BACKGROUND/AIMS: The aim of this study is, therefore, to classify appendiceal
      serrated polyps in a large case series with respect to the recent World Health
      Organization classification using diagnostic criteria provided for colorectal
      serrated polyps. MATERIALS AND METHODS: A total of 960 appendix specimens
      diagnosed between 2005 and 2010 were reviewed retrospectively, and cases
      presenting with a polyp with serrated morphology were classified with reference
      to the recent World Health Organization criteria. Histologic criteria comprised
      architectural features of the crypts, including serration, branching, basal
      dilatation, inverted T- or L-shaped crypts together with cytologic features
      comprising a mucin pattern, dysplasia, in terms of pseudostratification and
      nuclear atypia, mitoses in the upper crypts, and cytoplasmic eosinophilia.
      RESULTS: A total of 71 cases (7.39%) were diagnosed as serrated polyps, including
      36 (50.7%) hyperplastic polyps, 33 (46.48%) sessile serrated adenoma/polyps, and
      2 (2.81%) traditional serrated adenomas. There were 32 males and 39 females with
      an age range of 2 to 82 years. Histology revealed that the majority of both
      hyperplastic polyps (63.9%) and sessile serrated adenomas/polyps (74.3%) involved
      the entire appendiceal circumference. Basal dilatation (94.3%), basal serration
      (94.3%), T-/L-shaped crypts (94.3%), and ectopic crypts (68.6%) were
      significantly more commonly observed in sessile serrated adenomas/polyps compared
      to hyperplastic polyps. Dysplasia was observed in 31.4% of sessile serrated
      adenomas/polyps, while hyperplastic polyps did not show dysplasia. CONCLUSION:
      The results of the present study suggest that appendiceal serrated polyps,
      despite bearing many similarities with their colorectal counterparts, may have
      some special features due to the anatomic uniqueness of the organ itself and also
      the polyps arising from its mucosal lining.

PMID- 24918128
TI  - Acute liver failure in Turkey: a systematic review.
AB  - BACKGROUND/AIMS: To present the causes of acute liver failure in Turkey.
      MATERIALS AND METHODS: [corrected] International and national medical research
      databanks were searched for publications related to acute liver failure and
      originating from Turkey. Patients in the databank of acute liver failure of our
      center were also added to this literature search. Patients were evaluated for
      age, gender, etiology, treatment modality, and outcomes. RESULTS: A total of 308
      patients were analyzed. Hepatitis A (20.9%) for children and hepatitis B (34.7%)
      for adults were the most common causes of acute liver failure. Cryptogenic (18%)
      and metabolic (14%) reasons were the followings. Wilson's disease was the most
      common cause of metabolic diseases. Mushroom intoxication was the most frequent
      factor of toxic liver failure for both adults and children (13%). Firework
      intoxication, including yellow phosphorus, is an indigenous factor. Anti
      tuberculosis agents (3.2%) were the main cause of drug-induced acute liver
      failures (9%). Paracetamol was responsible for only 0.7% of all acute liver
      failures. Survival of the transplanted patients (n=118) was better than the non
      transplanted patients (n=178) (65% vs. 36% respectively, p<0.001) CONCLUSION:
      Preventable causes of acute liver failure in Turkey include hepatitis viruses and
      intoxication. Active vaccination and public awareness can decrease the number of
      acute liver failures. Paracetamol is not an emerging reason for acute liver
      failure in Turkey now, but selling it over the counter may increase the risks.

PMID- 24918129
TI  - Drug- and herb-induced liver injury: a case series from a single center.
AB  - BACKGROUND/AIMS: Drug-induced liver injury (DILI) is common worldwide and has a
      potentially fatal outcome. It accounts for more than half of the cases of acute
      liver failure in the United States. Herb-induced liver injury (HILI) is a less
      documented condition but a growing problem. We present here the clinical
      characteristics and outcome of patients with drug- and herb-induced liver injury
      from our center. MATERIALS AND METHODS: In this 4-year retrospective study, 82
      patients in whom there was a causal or highly probable relationship between
      herbal medicine or drug use and liver disease are presented. RESULTS: The mean
      age of patients was 43.1+/-14.8 years; sexual distribution was 53 females and 29
      males. The major cause of hepatotoxicity was drugs (87.8%), with herbal medicine
      accounting for 12.2%. The leading causative agents were nonsteroidal anti
      inflammatory drugs (NSAIDs) (23.1%), followed by antibiotics (19.5%). The pattern
      of hepatotoxicity was hepatocellular in 35 patients (42.6%), mixed in 28 (34.1%),
      and cholestatic in 19 patients (23.1%). Teucrium polium (known popularly as felty
      germander), which is a traditionally used herbal medicine of the Labiatae family
      in our region, was the most common cause of herb-induced liver injury and
      responsible in 7 of 10 herbal hepatotoxic cases. Acute liver failure developed in
      3 patients (two patients related with flurbiprofen and diclofenac and one patient
      due to an isoniazid-rifampicin combination). CONCLUSION: Antibiotics and NSAIDs
      were the most common etiologic agents for drug-induced liver injury.
      Surprisingly, herbs follow these groups of drugs and must be questioned more
      carefully.

PMID- 24918130
TI  - A retrospective review of children with gallstone: single-center experience from
      Central Anatolia.
AB  - BACKGROUND/AIMS: To evaluate children with gallstone in respect to demographic
      features, type of presentation, predisposing risk factors, laboratory features,
      complications, and outcome. MATERIALS AND METHODS: Overall, 124 children with
      sonographically diagnosed gallstone were stratified into group 1 (symptomatic)
      and group 2 (asymptomatic). The data on demographic features, predisposing risk
      factors, laboratory features, complications, and outcome were collected from
      medical charts and compared by using convenient statistical methods. RESULTS:
      There were 76 (61%) children in group 1. Females were significantly older than
      males at the time of diagnosis (p=0.001). After adjusting for age and sex,
      asymptomatic presentation was associated with hemolytic anemia (r=346, <0.001)
      and being an oncologic patient (r=248, p=0.006). No risk factor was specifically
      associated with having a symptomatic presentation. Sixteen children (12.9%)
      developed complications: 14 (18.4%) in group 1 and 2 (4.2%) in group 2 (p=0.027).
      Gallstone resolution was detected in 20 (29.4%) and 10 children (23.3%) in groups
      1 and 2, respectively (p=0.477). Resolution was observed in 43.8% of children
      with ceftriaxone-associated gallstone. The rate of resolution with
      ursodeoxycholic acid (UDCA) was similar to that observed with expectant
      management. Gallstone resolution was evident in 9 infants (50.0%) and was
      significantly higher than children over 2 years of age (21 out of 106 children,
      19.8%) (p=0.006). The most important factor associated with gallstone resolution
      was to be an infant (<2 years of age) at the time of diagnosis (OR: 3.1; 95% CI:
      1.1-8.8; p=0.034). CONCLUSION: Ceftriaxone-associated gallstones are most likely
      to resolve but do not always undergo spontaneous resolution. UDCA treatment seems
      to be ineffective. Young age is a favorable factor for gallstone resolution. The
      rate of complications in children with asymptomatic presentation is considerably
      low. Thus, clinical follow-up rather than surgical intervention is suggested in
      children with asymptomatic presentation and in infants.

PMID- 24918131
TI  - Increased frequency of gallbladder stone and related parameters in hemodialysis
      patients.
AB  - BACKGROUND/AIMS: The prevalence of gallbladder stone (GBS) is shown to be
      increased in some studies in patients with chronic kidney disease (CKD).
      Nevertheless, some other studies did not confirm these findings. The
      controversial results about the prevalence of GBS in hemodialysis (HD) patients
      demand new studies to search GBS prevalence and associating risk factors in HD
      patients. In the present study, we aimed to investigate GBS prevalence and risk
      factors in our HD patients. MATERIALS AND METHODS: A total of 104 HD and 149
      control patients were involved. Complete physical examinations, including
      measurements of dry body weight and height, were done. Abdominal ultrasonography
      was conducted by the same experienced radiologist. Blood samples were drawn via
      venipuncture from the study participants after they had fasted overnight just
      before a midweek hemodialysis session for laboratory examinations. RESULTS: The
      prevalence of GBS in HD patients was 34.6 % (36/104), and that was significantly
      higher than that of control group 12.9% (17/149; p=0.0001). In all study
      participants (HD patients and control group), patients with GBS were older than
      patients with no GBS (63.2+/-14.2 vs 53.7+/-16.7; p=0.0001). However, in HD
      patients, mean age was similar in patients with GBS and no GBS (64.3+/-13.8 vs
      60.1+/-16.6; p>0.05). Patients with GBS had a higher prevalence of units of blood
      transfusions than patients with no GBS in hemodialysis patients (2.0+/-2.9 vs
      0.9+/-1.3; p=0.047) CONCLUSION: The present study showed an increased prevalence
      of GBS in HD patients compared to healthy controls. The number of blood
      transfusions and autonomic neuropathy may be responsible for the increased
      prevalence of GBS in HD patients.

PMID- 24918132
TI  - Multiple orifices are better than single in the endoscopic treatment of
      pancreatic pseudocysts.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the surgical drainage of
      large, symptomatic pancreatic cysts (>5 cm) with single- and multi-channel
      endoscopic drainage. MATERIALS AND METHODS: In the period 2005-2010, we treated
      112 patients with post-inflammatory pancreatic cysts. Thirty-six patients
      underwent surgical internal drainage. The remaining group of patients was treated
      endoscopically. In 28 of them, drainage was performed by anastomosing the cyst to
      the gastrointestinal tract using a single pig tail drain and then widening the
      channel to a diameter of 15 mm. Forty-eight patients underwent multi-channel
      cystic drainage. It consisted of connecting the cyst to the stomach and/or
      duodenum using at least 3 drains. Each connection was widened to a minimum
      diameter of 15 mm to ensure free drainage of the morphotic elements of the cyst.
      Each procedure was preceded by abdominal computed tomography to determine the
      exact location of the cyst in relation to the gastrointestinal tract and a
      Doppler ultrasound scan to determine the location of the blood vessels modeling
      on its surface. RESULTS: In 48 patients with multi-channel drainage, there was no
      obstruction of the anastomosis, and cysts closed within 4 months. The drains were
      removed after about 3 months. The created channels were patent for about 3-4
      weeks, which was enough to completely close the cyst. CONCLUSION: Multi-channel
      endoscopic anastomosis of pancreatic cyst to the gastrointestinal tract is a very
      effective method for drainage of large post-inflammatory pancreatic cysts,
      comparable in terms of effectiveness with the surgical method but less invasive.

PMID- 24918133
TI  - South Korean endoscopists' attitudes toward endoscopic ultrasound for the
      evaluation of gastrointestinal diseases.
AB  - BACKGROUND/AIMS: Despite the common use of endoscopic ultrasound (EUS) for
      various gastrointestinal diseases in Asia, little is known about Asian
      endoscopists' attitudes toward the practice. The aim of our study was to provide
      a profile of Korean endoscopists' attitudes toward EUS use. MATERIALS AND
      METHODS: Self-administered questionnaires were distributed to endoscopists who
      attended the 4th EndoFest symposium of the Korean Society of Gastrointestinal
      Endoscopy on March 24, 2012. We evaluated opinions on the need for EUS for
      assessing gastrointestinal diseases and the perceived barriers to widespread EUS
      use. RESULTS: Data from 214 (32.4%) responders were analyzed. Positive opinions
      (agree plus strongly agree) were given on the need for EUS in the evaluation of
      the following gastrointestinal diseases were: subepithelial tumor (94.9%), early
      esophageal cancer (88.8%), early gastric cancer (86%), pancreatic cancer (84.1%),
      early rectal cancer (83.6%), gallbladder polyp (73.4%), advanced esophageal
      cancer (47.7%), colon cancer (32.2%), advanced gastric cancer (31.8%), and
      advanced rectal cancer (28.5%). Significant differences were observed when they
      were asked about the need for EUS with respect to early versus advanced cancers
      of the esophagus, stomach, and rectum (all p<0.001). The most commonly cited
      barrier to widespread use of EUS was lack of experienced endosonographers
      (66.2%). CONCLUSION: This is the first study to assess Korean attitudes toward
      using EUS for evaluating gastrointestinal diseases. Korean endoscopists highly
      value the use of EUS in the evaluation of early esophageal, gastric, and rectal
      cancers, as well as subepithelial lesions.

PMID- 24918134
TI  - The attitude of Asian endoscopist toward endoscopic ultrasonography.

PMID- 24918135
TI  - Analysis of cases with tuberculous peritonitis: a single-center experience.
AB  - BACKGROUND/AIMS: Tuberculous peritonitis (TP) is a rare form of tuberculosis and
      is caused by peritoneal involvement with Mycobacterium tuberculosis. A
      distinctive correlation exists between socioeconomic state and disease
      prevalence. We aimed to evaluate the clinical, laboratory, and radiological
      findings of patients with TP. MATERIALS AND METHODS: We conducted a retrospective
      study in patients with peritoneal tuberculosis from January 2004 to October 2008
      at Yuzuncu Yil University Medical School Education and Research Hospital. During
      this time, the data of 21 patients (17 females) with TP were reviewed. RESULTS:
      Fever, abdominal pain, and anorexia were the most common symptoms. An analysis of
      ascites showed lymphocyte predominance and low albumin gradient in all patients.
      Patients with TP had a median ascites adenosine deaminase (ADA) level of 139 U/L
      (range, 25 to 303U/L). Peritoneal involvement (wet peritonitis) was seen in all
      the cases. Following 6-month administration of combined anti-TBC treatment, mean
      serum CA-125 levels were within the normal range among patients who had
      previously higher serum CA-125 level. Mortality rate in the total cases was 4.6%.
      CONCLUSION: Peritoneal tuberculosis should be considered in the differential
      diagnosis of exudative ascites in eastern Turkey. A high level of suspicion is
      required, especially in high-risk populations living in rural areas. ADA seems to
      be a sufficient, safe, and inexpensive method to perform the diagnosis of
      peritoneal tuberculosis. Serum CA-125 levels may play a key role to support the
      diagnosis as well as disease management of TP.

PMID- 24918136
TI  - Understanding tuberculous peritonitis: a difficult task to overcome.

PMID- 24918137
TI  - Comparison of WHO 2000 and WHO 2010 classifications of gastroenteropancreatic
      neuroendocrine tumors.
AB  - BACKGROUND/AIMS: Grading and staging are important in gastroenteropancreatic
      neuroendocrine tumors for directing treatment. In this study, we evaluated the
      histopathological parameters of gastroenteropancreatic neuroendocrine tumors and
      statistically analyzed the correlations of these parameters between the World
      Health Organization (WHO) 2000 and 2010 classifications. MATERIALS AND METHODS: A
      total of 77 cases diagnosed as neuroendocrine tumors were included in the study.
      Cases were classified according to the WHO 2000 and WHO 2010 classification
      systems, and the differences and correlations between the two systems were
      discussed. RESULTS: Among the 50 cases that were diagnosed as well-differentiated
      neuroendocrine tumor according to WHO 2000, 45 were found to be Grade 1 and 5
      were found to be Grade 2 according to the WHO 2010 classification. Among the 8
      cases with well-differentiated neuroendocrine carcinoma according to WHO 2000; 5
      and 3 were Grade 1 and Grade 2, respectively, according to the WHO 2010
      classification. All of the 19 cases with poorly differentiated neuroendocrine
      carcinoma according to WHO 2000 were found to be Grade 3 according to the WHO
      2010 classification. No differences were found between the classifications in the
      poorly differentiated group with a full correlation between the two
      classifications. CONCLUSION: Although WHO 2000 seems to be a better
      classification to predict prognosis, since it is based on various parameters,
      such as depth of invasion, angiolymphatic invasion, and presence of metastasis,
      it was concluded that there was no difference between the WHO 2000 and WHO 2010
      classification, which is based on only the number of mitoses and Ki-67
      proliferation index.

PMID- 24918138
TI  - Spontaneous giant splenic hydatid cyst rupture causing fatal anaphylactic shock:
      a case report and brief literature review.
AB  - Hydatid disease is a parasitic infection characterized by cyst formation in any
      organ, although the liver and lungs are most commonly involved. Hydatid disease
      of the spleen is uncommon, representing <8% of all human hydatid diseases.
      Splenic hydatid cysts usually coexist with liver hydatid cysts (secondary form),
      although the spleen is the primary location (primary form) in some cases. The
      clinical signs and symptoms of splenic hydatid cysts depend on their size,
      relationship with adjacent organs, and complications. One of the complications of
      splenic hydatid cysts is cyst rupture either after trauma or spontaneously as a
      result of increased intracystic pressure. These cysts may rupture into a hollow
      organ, through the diaphragm into the pleural cavity, or directly into the
      peritoneal cavity. A splenic hydatid cyst that ruptures into the peritoneal
      cavity may cause complications, including signs of peritoneal irritation,
      urticaria, anaphylaxis, and death, as in our case. Therefore, a hydatid cyst
      rupture requires both emergency surgery and careful postoperative care. In this
      study, we present a case of a giant splenic hydatid cyst that ruptured into the
      peritoneal cavity without any trauma. A review of cases reported in the English
      literature about splenic hydatid cyst perforation is also discussed. 

PMID- 24918139
TI  - An unusual cause of duodenal obstruction: mesenteric fibromatosis in a patient
      with type I Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - Patients with mesenteric fibromatosis (MF) are clinically asymptomatic, with
      little or no focal symptoms until later in their course, at which time they
      complain of pain, abdominal discomfort, constipation, vomiting, abdominal mass,
      weight loss, and symptoms due to organ compression. Generally, it occurs as an
      abdominal mass but may also present in many different ways. In some cases,
      trauma, previous abdominal surgery, and hormonal stimulation (such as estrogen)
      may play a role in onset of this neoplasm. Patients with Mayer-Rokitansky-Kuster
      Hauser syndrome present primary amenorrhea and may have some other anomalies,
      including hearing defects, heart defects, skeletal deformities, and genital
      neoplastic diseases. We diagnosed duodenal obstruction due to MF in a patient
      with type I Mayer-Rokitansky-Kuster-Hauser syndrome. 

PMID- 24918140
TI  - A case of ulcerative colitis with digital arterial thrombosis.
AB  - Thromboembolic events are rare in the course of ulcerative colitis and related
      with the activity of the disease. These complications are especially seen in
      young patients and cause high mortality and morbidity. Arterial thrombotic
      complications are less frequent and are usually seen after a surgical procedure.
      Here, we present a 36-year-old man with active ulcerative colitis presenting via
      digital arterial thrombosis and digital necrosis that was not associated with a
      surgical procedure. 

PMID- 24918141
TI  - A rare outcome of iron deficiency and pica: Rapunzel syndrome in a 5-year-old
      child iron deficiency and pica.
AB  - Bezoar is defined as the accumulation of organic or nonbiological substances
      inside the gastrointestinal system. Trichobezoars are the most frequently
      detected ones and are mostly present in patients with neuropsychiatric disorders.
      The continuance of the trichobezoar tail-shaped extension over the duodenum and
      jejunum is described in Rapunzel syndrome. Both conditions are rarely reported in
      children. The present case submitted here is related to a 5-year-old girl
      referred with an abdominal mass and anemia, diagnosed with Rapunzel syndrome and
      developing trichobezoar due to iron deficiency and pica. 

PMID- 24918142
TI  - Endoscopic repair of duodenal perforation with over-the-scope clipping system and
      endoclips: a case report.
AB  - Herein, we present an endoscopic repair of iatrogenic duodenal perforation by
      over-the-scope clipping system (OTSC) and endoclips in an 84-year-old woman that
      occurred during linear endosonography (EUS) examination. One OTSC and 8 clips
      were used for repairing the perforation hole. After 3 days in the intensive care
      unit (ICU) by chest tube and without oral feeding, she was discharged from the
      hospital at 6. admission day, and she also had an acute coronary attack during 4.
      hospital day. OTSC and clipping devices are very useful for repair of iatrogenic
      perforations, especially in older patients who have comorbid diseases and who can
      not tolerate the surgery. 

PMID- 24918143
TI  - Metastasis of carcinoid tumor to the transplanted liver graft: a rare case
      report.
AB  - In this study, we present a rare case of gastrointestinal carcinoid tumor that
      metastasized to a transplanted liver graft. A 14-year-old female patient
      suffering from cryptogenic cirrhosis had undergone liver transplantation. The
      liver was received from a deceased donor. She presented to our clinic with
      complaints of abdominal pain, diarrhea, flushing, fatigue, and syncope four years
      after transplantation. On multislice computed tomography, multiple masses ranging
      from 1 cm to 4 cm in size were detected in both lobes of the transplanted liver.
      Biopsy from both lobes revealed carcinoid tumor. The primary tumor could not be
      localized, and a colonoscopy was scheduled. As the patient refused an invasive
      investigation, octreotide therapy was begun. Her symptoms related to the
      carcinoid tumor diminished following initiation of the octreotide therapy. During
      the fifth year of octreotide therapy, a whole-body positron emission tomography
      (PET CT) with 10 mCi F-18 fludeoxyglucose (FDG) showed an increase in the
      metabolic activity with a SUVmax value of 8 at the localization site, consistent
      with the ileocecal region. The findings were considered secondary, as the
      carcinoid tumor originated from the appendix or distal ileum. Again, the patient
      again refused endoscopic investigations and continued the follow-up visits. To
      our knowledge, this is the only reported case in the scientific literature of a
      carcinoid tumor that metastasized to a transplanted liver. 

PMID- 24918144
TI  - Isolated hepatic tuberculosis: a rare cause of hepatic mass lesions.
AB  - Hepatic tuberculosis usually accompanies pulmonary and extrapulmonary
      tuberculosis. Although isolated hepatic tuberculosis is a very rare condition, it
      should be considered in the differential diagnosis of a hepatic mass. Here, we
      report a 42-year-old woman presenting with weight loss, fever, night sweats, and
      a hepatic mass on the abdominal ultrasonography and magnetic resonance imaging
      (MRI). Ultrasonography-guided percutaneous needle biopsy demonstrated a caseating
      granuloma with epithelioid histiocytes and giant cells compatible with the
      diagnosis of tuberculosis. The patient was treated with four anti-tuberculous
      drugs for 1 year. She recovered clinically, and her post-treatment abdominal MRI
      was normal. 

PMID- 24918145
TI  - Chronic hepatitis in a patient with rigid spine myopathy: cause or just an
      association?

PMID- 24918146
TI  - A rare ileal tumor causing anemia and intussusception: inflammatory fibroid
      polyp.

PMID- 24918147
TI  - Diagnostic usefulness of technetium-99m-pertechnetate SPECT in a patient with
      Meckel's diverticulum.

PMID- 24918148
TI  - Crimean-Congo hemorrhagic fever presenting with gastrointestinal manifestations:
      two cases.

PMID- 24918149
TI  - Can "DNA-based stool tests" replace colonoscopy in screening for colon cancer?

PMID- 24918150
TI  - Antiviral therapy is not enough to prevent hepatocellular carcinoma development
      in patients with chronic hepatitis B.

PMID- 24918151
TI  - Does long-term metformin usage reduce gastric cancer risk?

PMID- 24918152
TI  - Gut microbiota modulation in cirrhosis: a new frontier in hepatology.

PMID- 24918153
TI  - Markers of endothelial dysfunction and inflammation predict progression of
      diabetic nephropathy in African Americans with type 1 diabetes.
AB  - African Americans with early-onset type 1 diabetes mellitus are at a high risk
      for severe diabetic nephropathy and end-stage renal disease. In order to
      determine whether baseline plasma levels of inflammatory markers predict
      incidence of overt proteinuria or renal failure in African Americans with type 1
      diabetes mellitus, we re-examined data of 356 participants in our observational
      follow-up study of 725 New Jersey African Americans with type 1 diabetes. At
      baseline and 6-year follow-up, a detailed structured clinical interview was
      conducted to document medical history including kidney dialysis or transplant,
      other diabetic complications, and renal-specific mortality. Plasma levels of 28
      inflammatory biomarkers were measured using a multiplex bead analysis system.
      After adjusting for baseline age, glycohemoglobin, and other confounders, the
      baseline plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) in
      the upper two quartiles were, respectively, associated with a three- to fivefold
      increase in the risk of progression from no albuminuria or microalbuminuria to
      overt proteinuria. Baseline plasma levels of the chemokine eotaxin in the upper
      quartile were significantly associated with a sevenfold increase in risk of
      incident renal failure. These associations were independent of traditional risk
      factors for progression of diabetic nephropathy. Thus, in type 1 diabetic African
      Americans, sICAM-1 predicted progression to overt proteinuria and eotaxin
      predicted progression to renal failure. 

PMID- 24918155
TI  - The role of bioimpedance and biomarkers in helping to aid clinical decision
      making of volume assessments in dialysis patients.
AB  - Bioimpedance analysis (BIA) derives two main pieces of information--total tissue
      fluid content, which when referring to the whole patient is equivalent to the
      total body water (TBW), and cell mass, which in the limbs mainly reflects muscle.
      The relationship between these measures, expressed in different ways, is abnormal
      in dialysis patients due to muscle wasting combined with tissue overhydration. In
      both dialysis modalities this is associated with aging, comorbidity, and
      inflammation, and there is a conflict between achieving euvolemia to improve
      blood pressure control and prevent left ventricular hypertrophy on one hand, but
      risking episodes of hypovolemia and loss of residual renal function on the other.
      In peritoneal dialysis, the situation is exacerbated by hypoalbuminemia, whereas
      in hemodialysis BIA is unable to distinguish between the plasma volume and tissue
      edema components of interdialytic weight gain. In longitudinal studies BIA can
      identify changes in hydration following a defined intervention, and spontaneous
      loss in TBW consequent on muscle wasting not appreciated clinically, resulting in
      a failure to sufficiently reduce the dry weight. Cardiac biomarkers provide
      additional information but it is not clear whether this reflects fluid status or
      underlying structural organ damage. Intervention studies are now needed that show
      how this information is best used to improve patient outcomes, including
      meaningful end points such as hospitalization and survival.

PMID- 24918154
TI  - Albumin-induced podocyte injury and protection are associated with regulation of
      COX-2.
AB  - Albuminuria is both a hallmark and a risk factor for progressive glomerular
      disease, and results in increased exposure of podocytes to serum albumin with its
      associated factors. Here in vivo and in vitro models of serum albumin-overload
      were used to test the hypothesis that albumin-induced proteinuria and podocyte
      injury directly correlate with COX-2 induction. Albumin induced COX-2, MCP-1,
      CXCL1, and the stress protein HSP25 in both rat glomeruli and cultured podocytes,
      whereas B7-1 and HSP70i were also induced in podocytes. Podocyte exposure to
      albumin induced both mRNA and protein and enhanced the mRNA stability of COX-2, a
      key regulator of renal hemodynamics and inflammation, which renders podocytes
      susceptible to injury. Podocyte exposure to albumin also stimulated several
      kinases (p38 MAPK, MK2, JNK/SAPK, and ERK1/2), inhibitors of which (except
      JNK/SAPK) downregulated albumin-induced COX-2. Inhibition of AMPK, PKC, and
      NFkappaB also downregulated albumin-induced COX-2. Critically, albumin-induced
      COX-2 was also inhibited by glucocorticoids and thiazolidinediones, both of which
      directly protect podocytes against injury. Furthermore, specific albumin
      associated fatty acids were identified as important contributors to COX-2
      induction, podocyte injury, and proteinuria. Thus, COX-2 is associated with
      podocyte injury during albuminuria, as well as with the known podocyte protection
      imparted by glucocorticoids and thiazolidinediones. Moreover, COX-2 induction,
      podocyte damage, and albuminuria appear mediated largely by serum albumin
      associated fatty acids. 

PMID- 24918156
TI  - The relationship between estimated sodium and potassium excretion and subsequent
      renal outcomes.
AB  - Patients are often advised to reduce sodium and potassium intake, but supporting
      evidence is limited. To help provide such evidence we estimated 24 h urinary
      sodium and potassium excretion in 28,879 participants at high cardiovascular risk
      who were followed for a mean of 4.5 years in the ONTARGET and TRANSCEND trials.
      The primary outcome was eGFR decline of 30% or more or chronic dialysis.
      Secondary outcomes were eGFR decline of 40% or more or chronic dialysis, doubling
      of serum creatinine or chronic dialysis, an over 5%/year loss of eGFR,
      progression of albuminuria, and hyperkalemia. Multinomial logit regression with
      multivariable fractional polynomials, adjusted for confounders, determined the
      association between urinary sodium and potassium excretion and renal outcomes,
      with death as a competing risk. The primary outcome occurred in 2,052 (7.6%)
      patients. There was no significant association between sodium and any renal
      outcome (primary outcome odds ratio 0.99; 95% CI 0.89-1.09 for highest [median
      6.2 g/day] vs. lowest third [median 3.3 g/day]). Higher potassium was associated
      with lower odds of all renal outcomes (primary outcome odds ratio 0.74; 95% CI
      0.67-0.82 for highest [median 2.7 g/day] vs. lowest third [median 1.7 g/day],
      except hyperkalemia nonsignificant. Thus, urinary potassium, but not sodium,
      excretion predicted clinically important renal outcomes. Our findings do not
      support routine low sodium and potassium diets for prevention of renal outcomes
      in people with vascular disease with or without chronic kidney disease.

PMID- 24918157
TI  - TREM-1 regulates macrophage polarization in ureteral obstruction.
AB  - Chronic kidney disease (CKD) is an emerging worldwide public health problem.
      Inflammatory cell infiltration and activation during the early stages in injured
      kidneys is a common pathologic feature of CKD. Here, we determined whether an
      important inflammatory regulator, triggering receptor expressed on myeloid cells
      (TREM)-1, is upregulated in renal tissues collected from mouse ureteral
      obstruction-induced nephritis. TREM-1 is crucial for modulating macrophage
      polarization, and has a pivotal role in mediating tubular injury and interstitial
      collagen deposition in obstructive nephritis. Lysates from nephritic kidneys
      triggered a TREM-1-dependent M1 polarization ex vivo, consistent with the
      observation that granulocyte-macrophage colony-stimulating factor (GM-CSF)
      derived M1 macrophages express higher levels of TREM-1 in comparison with M-CSF
      derived cells. Moreover, agonistic TREM-1 cross-link significantly strengthens
      the inductions of iNOS and GM-CSF in M1 cells. These observations are validated
      by a strong clinical correlation between infiltrating TREM-1-expressing/iNOS
      positive macrophages and renal injury in human obstructive nephropathy. Thus,
      TREM-1 may be a potential diagnostic and therapeutic target in human kidney
      disease. 

PMID- 24918158
TI  - Improved prognosis of diabetic nephropathy in type 1 diabetes.
AB  - The natural history of diabetic nephropathy offered an average survival of only 5
      7 years. During the past decades, multiple changes in therapy and lifestyle have
      occurred. The prognosis of diabetic nephropathy after implementing stricter
      control of blood pressure (including increased use of long-term renin-angiotensin
      system inhibition), lipids, and glycemia, along with less smoking and other
      lifestyle and treatment advancements, is inadequately analyzed. To clarify this,
      we studied 497 patients with type 1 diabetes and diabetic nephropathy at the
      Steno Diabetes Center and compared them with previous data, obtained using
      identical criteria at our hospital. The glomerular filtration rate, measured
      yearly by 51Cr-EDTA plasma clearance, was a mean of 71 ml/min per 1.73 m2 at
      baseline. The mean glomerular filtration rate decline was significantly reduced
      by 19% (95% confidence interval 5-34) from previously 4.0 to 3.3 ml/min per 1.73
      m2/year. During a median follow-up of 9.1 years, 29% of participants doubled
      their plasma creatinine or developed end-stage renal disease. Mortality risk was
      similar to our prior study (hazard ratio 1.05 (0.76-1.43). However, after age
      adjustment, as both diabetes and nephropathy onset occurred later in life,
      mortality was reduced by 30%. Risk factors for decline in glomerular filtration
      rate, death, and other renal end points were generally in agreement with prior
      studies. Thus, with current treatment of nephropathy in type 1 diabetes, the
      prognosis and loss of renal function has improved along with better control of
      modifiable risk factors.

PMID- 24918159
TI  - Treating chronic pain: the need for non-opioid options.
AB  - Chronic pain is a prevalent problem that exacts a significant toll on society.
      The medical system has responded to this issue by implementing pain management
      services centered on opioid pharmacotherapy. However, for many chronic pain
      patients, the analgesic efficacy of long-term opioids is limited. Moreover,
      chronic exposure to opioids can result in opioid misuse, addiction, and risk of
      overdose. As such, non-opioid treatment options are needed. This article first
      provides a selective review of cognitive, affective, and psychophysiological
      mechanisms implicated in chronic pain to be targeted by novel non-opioid
      treatments. Next, it briefly details one such treatment approach, Mindfulness
      Oriented Recovery Enhancement, and describes evidence suggesting that this
      intervention can disrupt the risk chain linking chronic pain to prescription
      opioid misuse. 

PMID- 24918160
TI  - A combined Mossbauer, magnetic circular dichroism, and density functional theory
      approach for iron cross-coupling catalysis: electronic structure, in situ
      formation, and reactivity of iron-mesityl-bisphosphines.
AB  - While iron-bisphosphines have emerged as effective catalysts for C-C cross
      coupling, the nature of the in situ formed iron species, elucidation of the
      active catalysts and the mechanisms of catalysis have remained elusive. A
      combination of (57)Fe Mossbauer and magnetic circular dichroism (MCD)
      spectroscopies of well-defined and in situ formed mesityl-iron(II)-SciOPP species
      combined with density functional theory (DFT) investigations provides the first
      direct insight into electronic structure, bonding and in situ speciation of
      mesityl-iron(II)-bisphosphines in the Kumada cross-coupling of MesMgBr and
      primary alkyl halides using FeCl2(SciOPP). Combined with freeze-trapped solution
      Mossbauer studies of reactions with primary alkyl halides, these studies
      demonstrate that distorted square-planar FeMes2(SciOPP) is the active catalyst
      for cross-coupling and provide insight into the molecular-level mechanism of
      catalysis. These studies also define the effects of key reaction protocol
      details, including the role of the slow Grignard addition method and the addition
      of excess SciOPP ligand, in leading to high product yields and selectivities. 

PMID- 24918161
TI  - Corroboration of naringin effects on the intestinal absorption and
      pharmacokinetic behavior of candesartan cilexetil solid dispersions using in-situ
      rat models.
AB  - OBJECTIVE: The aim of this study was to corroborate the effects of naringin, a P
      glycoprotein inhibitor, on the intestinal absorption and pharmacokinetics of
      candesartan (CDS) from candesartan cilexetil (CAN) solid dispersions using in
      situ rat models. MATERIALS AND METHODS: Intestinal transport and absorption
      studies were examined by in-situ single pass perfusion and closed-loop models. We
      evaluated the intestinal membrane damage in the presence of naringin by measuring
      the release of protein and alkaline phosphatase (ALP). RESULTS AND DISCUSSION: We
      noticed 1.47-fold increase in Peff of CDS from freeze-dried CAN-loaded solid
      dispersions with naringin (15 mg/kg, w/w) when compared with freeze-dried solid
      dispersion without naringin using in-situ single pass intestinal perfusion model.
      However, no intestinal membrane damage was observed in the presence of naringin.
      Our findings from in-situ closed-loop pharmacokinetic studies showed 1.34-fold
      increase in AUC with elevated Cmax and shortened tmax for freeze-dried solid
      dispersion with naringin as compared to freeze-dried solid dispersion without
      naringin. CONCLUSION: This study demonstrated that increased solubilization
      (favored by freeze-dried solid dispersion) and efflux pump inhibition (using
      naringin), the relative bioavailability of CDS can be increased, suggesting an
      alternative potential for improving oral bioavailability of CAN.

PMID- 24918162
TI  - Sofosbuvir (Sovaldi) for the treatment of hepatitis C.
AB  - Hepatitis C (HCV) remains an important cause of chronic liver disease worldwide.
      Historically, treatment included pegylated-interferon and ribavirin with low
      efficacy and numerous side effects contributing to poor adherence and impairment
      of patients' well-being. The next step in developing better treatment regimens
      for HCV led to the development of the first-generation direct acting antivirals
      (DAAs). Although these DAAs improved efficacy, they also added substantial side
      effects. The next generation of DAAs include Simeprevir and Sofosbuvir (SOF)
      which not only further enhanced the efficacy of the regimens but also improve
      their safety profile. This review summarizes the current clinical experience with
      SOF. SOF, an HCV-specific uridine nucleotide analog which inhibits the NS5B
      polymerase, is now available in the USA, Canada and Europe. Clinical trials of
      SOF-containing regimens have shown that these regimens are safe, efficacious, and
      well-tolerated in all genotypes. Additionally, SOF is associated with improved
      patient reported outcomes. 

PMID- 24918165
TI  - A novel rhodopsin point mutation, proline-170-histidine, associated with sectoral
      retinitis pigmentosa.
AB  - Identification and classification of all retinitis pigmentosa (RP) causing
      mutations contribute to a better understanding of disease variants. In this
      report we describe a New Zealand family, of European heritage, affected by a
      sectoral type RP phenotype in association with a novel rhodopsin mutation
      (proline-170-histidine) in a highly conserved site.

PMID- 24918166
TI  - Indolo[2,3-b]carbazole synthesized from a double-intramolecular Buchwald-Hartwig
      reaction: its application for a dianchor DSSC organic dye.
AB  - A new synthetic strategy for indolo[2,3-b]carbazole via a double-intramolecular
      Buchwald-Hartwig reaction has been established. The N-alkylated indolo[2,3
      b]carbazole then was adopted as the geometry-fixed core for the synthesis of a
      new molecule (ICZDTA) bearing two bithiophene pi-bridged 2-cyanoacrylic acid
      groups as the bidentate anchor. The bidentate anchoring together with efficient
      HOMO (indolo[2,3-b]carbazole) -> LUMO (TiO2 nanocluster) electron transfer leads
      to the successful development of ICZDTA-based DSSC with a power conversion
      efficiency of 6.02%. 

PMID- 24918167
TI  - The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and
      simvastatin-induced myopathy: 2014 update.
AB  - Simvastatin is among the most commonly used prescription medications for
      cholesterol reduction. A single coding single-nucleotide polymorphism,
      rs4149056T>C, in SLCO1B1 increases systemic exposure to simvastatin and the risk
      of muscle toxicity. We summarize evidence from the literature supporting this
      association and provide therapeutic recommendations for simvastatin based on
      SLCO1B1 genotype. This article is an update to the 2012 Clinical Pharmacogenetics
      Implementation Consortium guideline for SLCO1B1 and simvastatin-induced myopathy.

PMID- 24918168
TI  - Cost-utility of chelators in transfusion-dependent beta-thalassemia major
      patients: a review of the pharmacoeconomic literature.
AB  - In the inherited hematologic disorder beta-thalassemia major, patients receive
      regular, lifelong blood transfusions, which carry excess iron that the body is
      unable to eliminate. Chelation therapy (deferoxamine, deferiprone, deferasirox or
      deferoxamine-deferiprone combination) is required to reduce iron accumulation in
      target organs and the associated morbidity and mortality. Each chelation regimen
      has a distinct safety/efficacy profile and particular costs associated with its
      use. This review aims to provide an overview of published cost-utility analyses
      of currently used chelation regimens, and to comment on the potential relevance
      of their findings in the USA market, where deferiprone has recently been
      introduced. 

PMID- 24918170
TI  - Reactive stepping behaviour in response to forward loss of balance predicts
      future falls in community-dwelling older adults.
AB  - BACKGROUND: a fall occurs when an individual experiences a loss of balance from
      which they are unable to recover. Assessment of balance recovery ability in older
      adults may therefore help to identify individuals at risk of falls. The purpose
      of this 12-month prospective study was to assess whether the ability to recover
      from a forward loss of balance with a single step across a range of lean
      magnitudes was predictive of falls. METHODS: two hundred and one community
      dwelling older adults, aged 65-90 years, underwent baseline testing of sensori
      motor function and balance recovery ability followed by 12-month prospective
      falls evaluation. Balance recovery ability was defined by whether participants
      required either single or multiple steps to recover from forward loss of balance
      from three lean magnitudes, as well as the maximum lean magnitude participants
      could recover from with a single step. RESULTS: forty-four (22%) participants
      experienced one or more falls during the follow-up period. Maximal recoverable
      lean magnitude and use of multiple steps to recover at the 15% body weight (BW)
      and 25%BW lean magnitudes significantly predicted a future fall (odds ratios 1.08
      1.26). The Physiological Profile Assessment, an established tool that assesses
      variety of sensori-motor aspects of falls risk, was also predictive of falls
      (Odds ratios 1.22 and 1.27, respectively), whereas age, sex, postural sway and
      timed up and go were not predictive. CONCLUSION: reactive stepping behaviour in
      response to forward loss of balance and physiological profile assessment are
      independent predictors of a future fall in community-dwelling older adults.
      Exercise interventions designed to improve reactive stepping behaviour may
      protect against future falls.

PMID- 24918169
TI  - Relationships between physical performance and knee and hip osteoarthritis:
      findings from the European Project on Osteoarthritis (EPOSA).
AB  - BACKGROUND: poor physical performance (PP) is known to be associated with
      disability, lower quality of life and higher mortality rates. Knee and hip
      osteoarthritis (OA) might be expected to contribute to poor PP, through joint
      pain and restricted range of movement. Both clinical and self-reported OA are
      often used for large-scale community and epidemiological studies. OBJECTIVE: to
      examine the relationships between hip and knee OA and PP in a large data set
      comprising cohorts from six European countries. METHODS: a total of 2,942 men and
      women aged 65-85 years from the Germany, Italy, Netherlands, Spain, Sweden and
      the UK were recruited. Assessment included an interview and clinical assessment
      for OA. PP was determined from walking speed, chair rises and balance (range 0
      12); low PP was defined as a score of <=9. RESULTS: the mean (SD) age was 74.2
      (5.1) years. Rates of self-reported OA were much higher than clinical OA.
      Advanced age, female gender, lower educational attainment, abstinence from
      alcohol and higher body mass index were independently associated with low PP.
      Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR
      (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38),
      respectively, with relationships robust to adjustment for the confounders above
      as well as pain. CONCLUSION: lower limb OA at the hip and knee is associated with
      low PP, and for clinical diagnosis relationships are robust to adjustment for
      pain. Those at highest risk have clinical OA at both sites.

PMID- 24918171
TI  - Plasticizing effect of ibuprofen induced an alteration of drug released from
      Kollidon SR matrices produced by direct compression.
AB  - The objectives of this study were to investigate the effect of storage
      temperature on drug release from matrices containing 10, 40 and 70% w/w ibuprofen
      in Kollidon(r) SR (KSR). The matrix tablets were produced by direct compression
      and then kept at 30 and 45  degrees C for 3 months. Drug release from the matrix
      tablets was examined after storage for 0, 1, 4 and 12 weeks. Scanning electron
      microscope was used to reveal physical appearance of the tablet surface at the
      respective time intervals. In addition, differential scanning calorimeter was
      used to investigate glass transition temperature (Tg) of ibuprofen in KSR at 0
      100% w/w based on the principle of Gordon-Taylor equation. At 45  degrees C, the
      dissolution of ibuprofen in KSR as well as the coalescence of polymer particles
      were observed to be higher than those of storage at 30  degrees C. The physical
      state of ibuprofen dispersed in the polymeric matrix and degree of polymer
      coalescence led to the variation of drug release. The coalescence of polymer
      particles was a result of the polymer transition from glassy to rubbery state
      according to water absorption of KSR and plasticizing effect of ibuprofen. The
      reduction of the Tg of ibuprofen blended with KSR could be better described by
      the Kwei equation, a modified version of Gordon-Taylor equation. 

PMID- 24918172
TI  - Formulation of cellulose film containing permeation enhancers for prolonged
      delivery of propranolol hydrocloride.
AB  - The aim of this study was to evaluate the capacity of cellulose films enriched
      with oleic acid and polysorbate 80 to enhance the transdermal permeation of
      propranolol hydrochloride. Polymeric films were prepared by casting and drying
      aqueous solutions of hydroxypropylmethylcellulose or carboxymethylcellulose and
      characterized in chemical-physical properties, such as drug content, thickness,
      morphology and water uptake capacity. In vitro transport experiments were
      performed in order to evaluate the permeation enhancing ability of oleic acid and
      polysorbate 80. All carboxymethylcellulose films showed lower cumulative amounts
      of drug permeated than hydroxypropylmethylcellulose. Moreover, films containing
      both oleic acid and polysorbate 80 provided a greater permeation in comparison to
      film without permeation enhancers or only with one of these. The results obtained
      confirm that propranolol hydrochloride permeation can be easily modulated by
      varying the cellulose and enhancer type used for film preparation. 

PMID- 24918173
TI  - Caco-2 cells permeability evaluation of nifuroxazide derivatives with potential
      activity against methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Throughout the period of evaluation and selection in drug development, the
      assessment of the permeability potential of a compound to achieve an efficient
      refinement of the molecular structure has been widely appraised by the transport
      of substances across cell monolayers. This study aims to develop in vitro assays
      through Caco-2 cells in order to analyze the permeability of 5-nitro-heterocyclic
      compounds analogues to nifuroxazide with antimicrobial activity, especially
      showing promising activity against multidrug-resistant Staphylococcus aureus
      (MRSA). Caco-2 cell monolayers cultivated for 21 days in Transwell(r) plates were
      used for the in vitro permeability assays. The quantification of the nifuroxazide
      derivatives in the basolateral chambers was performed by a validated high
      performance liquid chromatography with UV (HPLC-UV) method. Apparent permeability
      values (Papp) show that these compounds can be considered as new drug candidates
      with the potential to present high absorption in vivo, according to the
      classifications of Yee and Biganzoli. The thiophenic derivatives showed
      permeability values higher than the furanic ones, being AminoTIO the compound
      with the greatest potential for the development of a new drug against MRSA, since
      it showed the best cytotoxicity, permeability and solubility ratio among all the
      derivatives. 

PMID- 24918174
TI  - Consequences of emergency contraceptives: the adverse effects.
AB  - INTRODUCTION: Emergency contraception (EC) offers women an important strategy to
      prevent unintended pregnancy following intercourse. Despite the constant
      improvement of availability of different molecules and techniques already
      existing (Yuzpe regimen, levonorgestrel, intrauterine device) and the emergence
      of ulipristal acetate, the numbers of unintended pregnancies and unplanned births
      could still be reduced. AREAS COVERED: This review will evaluate all the
      information about the potential adverse effects and tolerability of each method
      of EC by putting them in balance with their safety and effectiveness. A
      literature search until December 2013 was performed to identify all trials
      studying the safety data available concerning EC. EXPERT OPINION: Different means
      of EC have been demonstrated to be generally safe and well tolerated. These data
      support women information in order to improve use and efficacy of EC.

PMID- 24918175
TI  - [Special aspects of breast cancer surgery in the elderly].
AB  - Due to the aging population of Western countries and the high-quality health care
      system, breast cancer in the elderly generally affects women of good or
      satisfactory performance status pursuing active lifestyle. Over the last decade,
      it became evident that, in contrast to previous dogmas, age alone cannot be the
      contraindication to standard oncological treatment, and adequate
      multidisciplinary therapy aiming full recovery rather than compromise treatment
      is required. A number of specific aspects needs to be taken into account
      regarding surgery, such as life expectancy, co-morbidities, individual mobility,
      mental and emotional status as well as family background, which may result in
      changes to the individual treatment plan. Objective evaluation of the above
      mentioned parameters necessitates a close co-operation of professions.
      Interestingly, the evidence-based protocols of modern oncology often originate
      from the generalizations of results from clinical trials representing younger
      population, due to the typical under representation of elderly patients in
      clinical studies. Clinical trials should be extended to elderly patients as well
      or should specifically aim this patient population. The authors of the present
      paper review the special oncological and reconstructive surgical aspects of
      breast cancer in the elderly, such as breast conserving surgery versus
      mastectomia, sentinel lymph node biopsy, axillary lymphadenectomy or the omission
      of surgery in axillary staging, and questions regarding implant based and
      autologous reconstructive techniques.

PMID- 24918176
TI  - [Psychological and biological background of the correlation between psoriasis and
      stress].
AB  - Stress is considered as a major contributor to the development and exacerbation
      of psoriasis by a significant proportion of patients and dermatologists. As both
      stressor and its effects are subject-dependent, thus extremely difficult to
      measure, our understanding of the exact role of stress in disease development was
      limited for a long time. In the past decade several new studies were carried out
      which expanded our knowledge on the pathophysiologic processes linking stress to
      psoriasis via with their objective measurements and the applied new techniques.
      The authors review the current literature of both psychological (alexithymia,
      personality, affect) and biological (cortisol, epinephrine, neurogenic
      inflammation) factors influencing stress perception and response in psoriasis.
      Results of recent investigations support previous reports about the interaction
      between stress and psoriasis with objective evidence. Knowing how effective
      stress-reducing psychopharmacologic and psychotherapeutic interventions are in
      the treatment of psoriasis the authors hope that this review contributes to a
      wider acceptance of the psychosomatic attitude in everyday dermatologic practice.

PMID- 24918177
TI  - [The effect of Kaqun-water on the immune parameters of healthy volunteers].
AB  - INTRODUCTION: Kaqun-water contains a high amount of stable oxygen, which absorbed
      through the skin and intestinal tract, increases tissue oxygenation. AIM: The aim
      of the authors was to evaluate the effect of 21 days of Kaqun-water treatment on
      the immune parameters of healthy volunteers. METHOD: Subpopulations of
      lymphocytes were determined by immune phenotyping, and CD25 and CD71 activation
      antigens were used to assess lymphocyte activation. Production of reactive oxygen
      intermediates was measured to determine the killing capacity of neutrophil
      granulocytes. Data was analysed with repeated measures ANOVA. RESULTS: The
      reactive oxygen intermediate production of neutrophils increased significantly in
      stimulated samples during three weeks of Kaqun-water treatment. The percent of
      activated, CD25 positive T and helper T cells, and the ratio of NK cells
      increased. CONCLUSIONS: The increase in oxygen concentration caused by Kaqun
      water treatment affects several immune functions: the killing potential of
      neurophil granulocytes is enhanced, the activation of lymphocytes shows an
      increased activity of immune function, and the elevated ratio of NK cells may
      help combat virally infected and tumorous cells.

PMID- 24918178
TI  - [Birth weight of Roma neonates: effect of biomedical and socioeconomic factors in
      Hungary].
AB  - INTRODUCTION: The last Hungarian study on birth weight of Roma neonates published
      in 1991 indicated -377 gram crude difference as compared to the general
      population. Exploration of this complex problem requires more sophisticated,
      multifactorial linear regression analysis. AIM: To compare Roma and non-Roma
      maternal and neonatal populations using biomedical and socioeconomic variables
      focusing on differences in the birth weight of the neonates. METHOD: Data
      collection with self-identified ethnicity was performed between 2009 and 2012 in
      five north and eastern counties of Hungary. The authors used the IBM-SPSS v.22
      program for Chi-square and t-probe and linear regression analysis. RESULTS: In
      the sample of Roma (n = 3103) and non-Roma (n = 8918) populations there was a
      disadvantage in birth weight in Roma neonates by 294 gram in crude terms, but the
      linear regression model reduced it to 92 gram by the ethnic variable.
      CONCLUSIONS: Biological (genetic) impact on the weight difference cannot be
      excluded, however, the multifactorial statistical analysis indicates the priority
      of socioeconomic factors and behavioural patterns.

PMID- 24918179
TI  - [Role of the infirmary at Sarospatak Calvinist College in the history of school
      hygiene].

PMID- 24918180
TI  - Accuracy of plantar electrodes compared with hand and foot electrodes in fat-free
      mass measurement.
AB  - This paper investigates the measurement of fat-free mass (FFM) by bioimpedance
      using foot-to-foot impedancemeters (FFI) with plantar electrodes measuring the
      foot-to-foot resistance R34 and hand-to-foot medical impedancemeters. FFM
      measurements were compared with corresponding data using Dual X-ray
      absorptiometry (DXA). Equations giving FFM were established using linear multiple
      regression on DXA data in a first group of 170 subjects. For validation, these
      equations were used on a second group of 86 subjects, and FFM were compared with
      DXA data; no significant difference was observed. The same protocol was repeated,
      but using electrodes on the right hand and foot in standing position to measure
      the hand to-foot resistance R13. Mean differences with DXA were higher for R13
      than for R34. Effect of electrode size and feet position on resistance was also
      investigated. R34 decreased when electrode area increased or if feet were moved
      forward. It decreased if feet were moved backward. A proper configuration of
      contact electrodes can improve measurement accuracy and reproducibility of FFI. 

PMID- 24918181
TI  - Evaluation of upper limb sense of position in healthy individuals and patients
      after stroke.
AB  - The aims of this study were to develop and evaluate reliability of a quantitative
      assessment tool for upper limb sense of position on the horizontal plane. We
      evaluated 15 healthy individuals (controls) and 9 stroke patients. A robotic
      device passively moved one arm of the blindfolded participant who had to actively
      move his/her opposite hand to the mirror location in the workspace. Upper-limb's
      position was evaluated by a digital camera. The position of the passive hand was
      compared with the active hand's 'mirror' position. Performance metrics were then
      computed to measure the mean absolute errors, error variability, spatial
      contraction/expansion, and systematic shifts. No significant differences were
      observed between dominant and non-dominant active arms of controls. All
      performance parameters of the post-stroke group differed significantly from those
      of controls. This tool can provide a quantitative measure of upper limb sense of
      position, therefore allowing detection of changes due to rehabilitation. 

PMID- 24918182
TI  - Data quality and completeness in a web stroke registry as the basis for data and
      process mining.
AB  - Electronic health records often show missing values and errors jeopardizing their
      effective exploitation. We illustrate the re-engineering process needed to
      improve the data quality of a web-based, multicentric stroke registry by
      proposing a knowledge-based data entry support able to help users to
      homogeneously interpret data items, and to prevent and detect treacherous errors.
      The re-engineering also improves stroke units coordination and networking,
      through ancillary tools for monitoring patient enrollments, calculating stroke
      care indicators, analyzing compliance with clinical practice guidelines, and
      entering stroke units profiles. Finally we report on some statistics, such as
      calculation of indicators for assessing the quality of stroke care, data mining
      for knowledge discovery, and process mining for comparing different processes of
      care delivery. The most important results of the re-engineering are an improved
      user experience with data entry, and a definitely better data quality that
      guarantees the reliability of data analyses. 

PMID- 24918183
TI  - Policy-based approach to emergency bio-data management for mobile healthcare.
AB  - In m-healthcare service, accurate detection and notification of emergency
      situation are critical to chronic patients' life. Since they are usually
      performed by a limited number of medical staff, it is difficult to simultaneously
      support many patients in real-time. This article presents an architecture to
      support the emergency bio-data management for m-healthcare service using
      personalized emergency policy. The salient feature of the proposed architecture
      is that the decision on emergency is made using personalized emergency policy.
      Specifically, the structure of the detailed system components has also been
      designed. The emergency condition of the individual bio-data collected from
      wireless body area network is detected automatically using personalized emergency
      policy. The message flow diagram based on the personalized emergency policy is
      described. This enables quick emergency rescue service provided to the patient
      both accurately and immediately. The prototype of proposed system has been built
      to demonstrate the design concept. 

PMID- 24918184
TI  - PM2: a partitioning-mining-measuring method for identifying progressive changes
      in older adults' sleeping activity.
AB  - As people age, their health typically declines, resulting in difficulty in
      performing daily activities. Sleep-related problems are common issues with older
      adults, including shifts in circadian rhythms. A detection method is proposed to
      identify progressive changes in sleeping activity using a three-step process:
      partitioning, mining, and measuring. Specifically, the original spatiotemporal
      representation of each sleeping activity instance was first transformed into a
      sequence of equal-sized segments, or symbols, via a partitioning process. A data
      mining-based algorithm was proposed to find symbols that are not present in all
      instances of a sleeping activity. Finally, a measuring process was responsible
      for evaluating the changes in these symbols. Experimental evaluation conducted on
      a group of datasets of older adults showed that the proposed method is able to
      identify progressive changes in sleeping activity. 

PMID- 24918185
TI  - Reducing hospital ICU noise: a behavior-based approach.
AB  - Noise in Intensive Care Units (ICUs) is gaining increasing attention as a
      significant source of stress and fatigue for nursing staff. Extensive research
      indicates that hospital noise also has negative impact on patients. The objective
      of this study was to analyze noise variations as experienced by both nursing
      staff and patients, to gain a better understanding of noise levels and
      frequencies observed in ICU settings over extended (week-long) durations, and to
      implement a low cost behavior modification program to reduce noise. The results
      of our study indicate that behavioral modification alone is not adequate to
      control excessive noise. There is a need for further research involving the
      supportive involvement by clinicians, ICU staff, along with effective medical
      device alarm management, and continuous process improvement methods. 

PMID- 24918186
TI  - Energy performance of medium-sized healthcare buildings in Victoria, Australia- a
      case study.
AB  - This paper investigates the energy performance of three medium-sized healthcare
      buildings in Victoria, Australia, that operate only during the daytime. The aim
      is to provide preliminary understanding of energy consumption in this particular
      typology in Australia in relation to the available benchmarks. This paper also
      identifies the differences of energy consumption between different functional
      areas within medium health facilities. Building features and operational
      characteristics contributing to the variations in healthcare energy performance
      are discussed. The total annual energy consumption data ranging from 167-306
      kWh/m(2) or 42-72 kWh/m(3) were compared against international data from various
      climatic zones. Some of the drivers of energy consumption were determined and
      potentials for energy and water conservation were identified. Comparison with
      international standards shows a possibility to achieve lower energy consumption
      in Victorian healthcare buildings.

PMID- 24918189
TI  - Photoinduced electron transfer in a dynamic supramolecular system with curved pi
      structures.
AB  - Photoinduced electron-transfer processes in a carbonaceous supramolecular
      combination of a tubular host and a C60 guest were investigated with time
      resolved transient absorption spectra upon laser flash photolysis. Following the
      formation of triplet charge-separated species via electron transfer from the host
      to the guest, a rapid back electron transfer proceeded to afford triplet C60. 

PMID- 24918187
TI  - Pooled results from 5 validation studies of dietary self-report instruments using
      recovery biomarkers for energy and protein intake.
AB  - We pooled data from 5 large validation studies of dietary self-report instruments
      that used recovery biomarkers as references to clarify the measurement properties
      of food frequency questionnaires (FFQs) and 24-hour recalls. The studies were
      conducted in widely differing US adult populations from 1999 to 2009. We report
      on total energy, protein, and protein density intakes. Results were similar
      across sexes, but there was heterogeneity across studies. Using a FFQ, the
      average correlation coefficients for reported versus true intakes for energy,
      protein, and protein density were 0.21, 0.29, and 0.41, respectively. Using a
      single 24-hour recall, the coefficients were 0.26, 0.40, and 0.36, respectively,
      for the same nutrients and rose to 0.31, 0.49, and 0.46 when three 24-hour
      recalls were averaged. The average rate of under-reporting of energy intake was
      28% with a FFQ and 15% with a single 24-hour recall, but the percentages were
      lower for protein. Personal characteristics related to under-reporting were body
      mass index, educational level, and age. Calibration equations for true intake
      that included personal characteristics provided improved prediction. This project
      establishes that FFQs have stronger correlations with truth for protein density
      than for absolute protein intake, that the use of multiple 24-hour recalls
      substantially increases the correlations when compared with a single 24-hour
      recall, and that body mass index strongly predicts under-reporting of energy and
      protein intakes. 

PMID- 24918190
TI  - Respiratory failure due to upper airway obstruction in children: use of the
      helmet as bridge interface.
AB  - Upper airway obstruction (UAO) can cause severe respiratory distress in young
      children by increasing inspiratory muscle load and decreasing alveolar
      ventilation, ultimately resulting in hypercapnia and hypoxemia which have long
      term negative cardiovascular effects. Although non-invasive continuous positive
      airway pressure (CPAP) improves gas exchange in these patients, use of
      conventional interfaces (nasal mask, nasal pillow and facial mask) may cause
      significant discomfort and lead to CPAP intolerance. We report five cases of
      children affected by UAO who experienced CPAP intolerance via application of
      conventional interfaces. Alternatively, we acutely applied helmet-CPAP which
      resulted in improved breathing pattern and gas exchange. Thereafter, patients
      received training with respect to a nasal CPAP interface, allowing successful
      long term treatment. In conclusion, these five clinical cases demonstrate that
      helmet-CPAP can be used acutely in children with UAO if compliance to
      conventional modalities is problematic, allowing for sufficient time to achieve
      compliance to nasal-CPAP. 

PMID- 24918191
TI  - Effect of analgesic modality on outcome following open liver surgery: a
      systematic review of postoperative analgesia.
AB  - Postoperative analgesia following liver resection remains controversial. The
      traditional standard of care of thoracic epidural is increasingly questioned due
      to perceived associated complications and delays to recovery. Evidence supporting
      alternative analgesic techniques is emerging however best practice is not yet
      established. This review aimed to evaluate the literature to assess the optimum
      analgesic technique following liver resection. A systematic review was conducted
      of trials evaluating analgesic methods in open liver surgery. Primary outcome was
      the postoperative complication rate. Secondary outcomes were length of stay and
      pain scores. Fourteen trials matching the inclusion criteria were analysed. No
      difference was observed in systemic complication rates between analgesic
      modalities. Epidural was associated with prolonged length of stay when compared
      with continuous wound infiltration and intrathecal morphine. Epidural offered
      equivalent or superior pain scores when compared to alternative techniques. In
      summary current evidence suggests alternative analgesic modalities may provide
      favorable recovery outcomes following liver surgery but consistent evidence is
      limited. Epidurals provide superior pain relief to alternatives but this does not
      translate into reduced length of stay or complication rate following liver
      surgery. 

PMID- 24918192
TI  - Is there a role for generic antiretroviral drugs in the United States?
AB  - The high cost of antiretroviral drugs has limited access to treatment for some
      HIV-infected patients in the United States and strained public resources. With
      the introduction of much cheaper generic versions of some of these agents, and
      with more to come in the next few years, the need increases to define the role of
      generic antiretroviral drugs in patient management. 

PMID- 24918193
TI  - Endovascular treatment of coarctation and related aneurysms.
AB  - Today, surgical repair has almost doubled the 30-year survival rate in patients
      with coarctation of the aorta (CoA), and 72% to 98% of patients now reach
      adulthood. Possible late complications include malignant hypertension, left
      ventricular dysfunction, aortic valve dysfunction, recurrent CoA, and aneurysm
      formation with risk of rupture. Treating postoperative CoA-related aneurysms with
      observation alone is associated with a mortality rate of 36%, compared with 9%
      for surgical repair. Even in the best surgeons' hands, aortic surgery has
      associated complications, and the complexity of reoperative surgery makes the
      risks substantially greater. For patients with CoA-related aneurysm, endovascular
      treatment constitutes a good alternative to reoperative surgery because it poses
      a lower risk of morbidity and mortality. Implanting an endograft has been shown
      to be successful in treating CoA and related aneurysms, producing excellent
      intermediate outcomes and minimal morbidity and mortality. Despite evidence that
      using covered stents improves outcomes, the superiority of any particular stent
      type has yet to be established. With a variety of endografts available, the
      decision of which stent to use depends on anatomy, availability, and operator
      preference.

PMID- 24918194
TI  - Clinical validation of 40-mmHg carotid stump pressure for patients undergoing
      carotid endarterectomy under general anesthesia.
AB  - BACKGROUND: The aim of this study was to validate a mean stump pressure (SP) of
      40 mmHg as the cut off threshold for shunting during carotid endarterectomy
      (CEA). METHODS: A prospective analysis of recently symptomatic carotid stenosis
      patients undergoing fast-track CEA under general anesthesia. An arbitrary cut-off
      threshold of 40 mmHg (mean) was defined as the indication for shunt insertion.
      With an SP<40 mmHg systemic blood pressure was increased 10-20% using
      sympathomimetic drugs. Patients with an SP>=40 mmHg CEA were operated without a
      shunt. A neurological observation scheme was filled out preoperatively by the
      anesthesiologist and postoperatively during the first 24 hours after surgery.
      Endpoints for validation of SP were per new transient ischemic attack (TIA) or
      stroke (ipsilateral or contralateral), hypoperfusion/hypoxia syndrome or death
      before discharge from hospital. RESULTS: One hundred and twenty consecutive CEAs
      were performed in recently symptomatic patients. A significant correlation
      between SP and the contralateral stenosis degree of internal carotid artery (ICA)
      was found in our study P=0.05. Sixteen patients (14%) had SP<40 mmHg after
      clamping the carotid arteries. Raising blood pressure intra-operatively by 10-20%
      reduced the incidence of shunt insertion to only three patients (80% reduction).
      Of the 120 CEAs, only 2.5% (95% CI 1-6%) of patients required shunt. There was no
      post-operative TIA or stroke in our study. Two patients (1.65%) suffered early
      TIA from ipsilateral ICA after discharge from the vascular unit. CONCLUSIONS:
      Using a mean SP of 40 mmHg as a threshold seems to be a safe, easy and cheap
      method for selective shunt insertion in fast track CEA under general anesthesia
      with a zero false-negative rate. Raising the systemic blood pressure by 10-20%
      during cross clamping increased SP above the threshold value 40 mmHg, thus
      avoiding shunt insertion in a number of patients.

PMID- 24918195
TI  - Retrograde recanalization of complex SFA lesions indications and techniques.
AB  - Femoro-popliteal segment is often characterized by diffuse and severe steno
      obstructive atheroclerotic disease. Most recent guidelines recommended
      endovascular techniques as a valid and safe treatment in highly symptomatic
      patients (Rutherford class 4 to 6) with complex femoropopliteal lesions (TASC C
      and D). Continuous technical development is increasing the efficacy of the
      endovascular technique with the introduction of new dedicated devices. In most
      complex situation also retrograde recanalization can be applied. The main
      indication to this technique is when conventional antegrade recanalisation fails
      or cannot be apply. The most common retrograde access is through the popliteal
      artery. However many operators do not like this approach due to the technical
      issue correlated to the patient position. Recently several reports have been
      published keeping the patient supine improving patient comfort and operator
      activity. This tehnique was also affected by several complications at the level
      of the popliteal puncture site, but those were resolved with the improvement of
      technique and operator skills. Hence several Authors described different variants
      of such technique (subintimal techniques, patient in supine position, puncture of
      the distal superficial femoral artery, tibial/pedal artery access) all obtaining
      an high rate of success with a low complication rate. In conclusion retrograde
      recanalization can be considered a safe and effective technique for complex
      femoral lesions. It is also less expensive than recanalisation devices, less time
      consuming and can increase the outcome due to the higher percentage of
      intraluminal recanalization. 

PMID- 24918196
TI  - TEVAR for chronic aortic dissection - is covering the primary entry tear enough?
AB  - Treatment-strategies for type B aortic dissection (TBAD) are rapidly developing
      towards endovascular treatment strategies. While TEVAR for acute TBAD shows
      favourable results, TEVAR in chronic TBAD following the same interventional
      strategies as in acute TBAD by covering the proximal entry-tear alone has shown
      unsatisfactory results with one third of the patients developing further false
      lumen growth and mortality of 36% at 3 years. This review article describes
      endovascular strategies and adjunctive techniques to prevent distal false-lumen
      back-flow in patients with chronic TBAD, as covering the proximal entry tear has
      proven insufficient. 

PMID- 24918197
TI  - A comparison of disproportionality analysis methods in national adverse drug
      reaction databases of China.
AB  - OBJECTIVE: Several disproportionality analysis methods are widely used for signal
      detection. The goal of this study was to compare the concordance of the
      performance characteristics of these methods in spontaneous reporting system of
      China. METHODS: Algorithms including reporting odds ratio (ROR), proportional
      reporting ratio (PRR) and information component (IC), a composite criterion
      previously used by Medicines and Healthcare Products Regulatory Agency (MHRA)
      were compared. Kappa coefficient was used as the gauge to test the concordance.
      Reports received in the year 2004 and 2005 were extracted for analysis in this
      study. RESULTS: After data processing, 361,872 reports representing 52,769
      combinations were analysed. The analysis generated 24,022, 22,646, 5637 and 5302
      signals of disproportionality by PRR, ROR, MHRA and IC, respectively. The kappa
      coefficient increased with the threshold of number of drug-adverse drug reactions
      (ADR) combination, and the coefficient exceeded 0.7 when the number of suspected
      drug-ADR exceeded 2. CONCLUSION: This study shows that different measures used
      are broadly comparable in spontaneous reporting system in China when two or more
      cases per combination have been collected.

PMID- 24918198
TI  - Leucine-rich repeat kinase 2 inhibitors: a review of recent patents (2011 -
      2013).
AB  - INTRODUCTION: Leucine-rich repeat kinase 2 (LRRK2) is a large (2527 residues)
      complex multi-domain protein that has GTPase and kinase domains. Autosomal
      dominant missense mutations in LRRK2 have been found in individuals with
      Parkinson's disease (PD) and are considered responsible for 1% of all cases of
      PD. Among the mutations confirmed to contribute to PD pathogenicity, G2019S is
      the most common cause of PD and it increases the kinase activity of LRRK2 by
      around threefold. LRRK2 has received considerable attention as a therapeutic
      target for PD, and LRRK2 inhibitors may help prevent and/or treat the disease.
      AREAS COVERED: LRRK2 inhibitors are being investigated by various industrial and
      academic institutions. The present review covers patents literature on small
      molecule LRRK2 inhibitors patented between 2011 and 2013. EXPERT OPINION:
      Currently, wild-type and mutant LRRK2 are being examined as therapeutic targets
      for PD. In testimony to the significance of these novel targets, over 20 patent
      applications related to LRRK2 have been filed in the last 3 years. Several
      distinct chemotypes have been reported to be LRRK2 inhibitors with very good
      potency. These compounds are being used to elucidate the physiological and
      pathophysiological functions of LRRK2, and some may even emerge as therapeutics
      for PD.

PMID- 24918200
TI  - Metabolomic strategies to map functions of metabolic pathways.
AB  - Genome sequencing efforts have revealed a strikingly large number of unannotated
      and uncharacterized genes that fall into metabolic enzymes classes, likely
      indicating that our current knowledge of biochemical pathways in normal
      physiology, let alone in disease states, remains largely incomplete. This
      realization presents a daunting challenge for post-genomic-era scientists in
      deciphering the biochemical and (patho)physiological roles of these enzymes and
      their metabolites and metabolic networks. This is further complicated by many
      recent studies showing a rewiring of normal metabolic networks in disease states
      to give rise to unique pathophysiological functions of enzymes, metabolites, and
      metabolic pathways. This review focuses on recent discoveries made using
      metabolic mapping technologies to uncover novel pathways and metabolite-mediated
      posttranslational modifications and epigenetic alterations and their impact on
      physiology and disease. 

PMID- 24918199
TI  - Interleukin-1beta mediates macrophage-induced impairment of insulin signaling in
      human primary adipocytes.
AB  - Adipose tissue expansion during obesity is associated with increased macrophage
      infiltration. Macrophage-derived factors significantly alter adipocyte function,
      inducing inflammatory responses and decreasing insulin sensitivity.
      Identification of the major factors that mediate detrimental effects of
      macrophages on adipocytes may offer potential therapeutic targets. IL-1beta, a
      proinflammatory cytokine, is suggested to be involved in the development of
      insulin resistance. This study investigated the role of IL-1beta in macrophage
      adipocyte cross-talk, which affects insulin signaling in human adipocytes. Using
      macrophage-conditioned (MC) medium and human primary adipocytes, we examined the
      effect of IL-1beta antagonism on the insulin signaling pathway. Gene expression
      profile and protein abundance of insulin signaling molecules were determined, as
      was the production of proinflammatory cytokine/chemokines. We also examined
      whether IL-1beta mediates MC medium-induced alteration in adipocyte lipid
      storage. MC medium and IL-1beta significantly reduced gene expression and protein
      abundance of insulin signaling molecules, including insulin receptor substrate-1,
      phosphoinositide 3-kinase p85alpha, and glucose transporter 4 and phosphorylation
      of Akt. In contrast, the expression and release of the proinflammatory markers,
      including IL-6, IL-8, monocyte chemotactic protein-1, and chemokine (C-C motif)
      ligand 5 by adipocytes were markedly increased. These changes were significantly
      reduced by blocking IL-1beta activity, its receptor binding, or its production by
      macrophages. MC medium-inhibited expression of the adipogenic factors and 
      stimulated lipolysis was also blunted with IL-1beta neutralization. We conclude
      that IL-1beta mediates, at least in part, the effect of macrophages on insulin
      signaling and proinflammatory response in human adipocytes. Blocking IL-1beta
      could be beneficial for preventing obesity-associated insulin resistance and
      inflammation in human adipose tissue. 

PMID- 24918201
TI  - Tissue-type plasminogen activator deficiency delays bone repair: roles of
      osteoblastic proliferation and vascular endothelial growth factor.
AB  - Further development in research of bone regeneration is necessary to meet the
      clinical demand for bone reconstruction. Recently, we reported that plasminogen
      is crucial for bone repair through enhancement of vessel formation. However, the
      details of the role of tissue-type plasminogen activator (tPA) and urokinase-type
      plasminogen activator (uPA) in the bone repair process still remain unknown.
      Herein, we examined the effects of plasminogen activators on bone repair after a
      femoral bone defect using tPA-deficient (tPA(-/-)) and uPA-deficient (uPA(-/-))
      mice. Bone repair of the femur was delayed in tPA(-/-) mice, unlike that in wild
      type (tPA(+/+)) mice. Conversely, the bone repair was comparable between wild
      type (uPA(+/+)) and uPA(-/-) mice. The number of proliferative osteoblasts was
      decreased at the site of bone damage in tPA(-/-) mice. Moreover, the
      proliferation of primary calvarial osteoblasts was reduced in tPA(-/-) mice.
      Recombinant tPA facilitated the proliferation of mouse osteoblastic MC3T3-E1
      cells. The proliferation enhanced by tPA was antagonized by the inhibition of
      endogenous annexin 2 by siRNA and by the inhibition of extracellular signal
      regulated kinase (ERK)1/2 phosphorylation in MC3T3-E1 cells. Vessel formation as
      well as the levels of vascular endothelial growth factor (VEGF) and hypoxia
      inducible factor-1alpha (HIF-1alpha) were decreased at the damaged site in tPA(-/
      ) mice. Our results provide novel evidence that tPA is crucial for bone repair
      through the facilitation of osteoblast proliferation related to annexin 2 and
      ERK1/2 as well as enhancement of vessel formation related to VEGF and HIF-1alpha
      at the site of bone damage. 

PMID- 24918203
TI  - A footprint of past climate change on the diversity and population structure of
      Miscanthus sinensis.
AB  - BACKGROUND AND AIMS: Miscanthus is a perennial C4 grass that is a leading
      potential feedstock crop for the emerging bioenergy industry in North America,
      Europe and China. However, only a single, sterile genotype of M. * giganteus
      (M*g), a nothospecies derived from diploid M. sinensis (Msi) and tetraploid M.
      sacchariflorus (Msa), is currently available to farmers for biomass production.
      To facilitate breeding of Miscanthus, this study characterized genetic diversity
      and population structure of Msi in its native range of East Asia. METHODS: A
      total of 767 accessions were studied, including 617 Msi from most of its native
      range in China, Japan and South Korea, and 77 ornamental cultivars and 43
      naturalized individuals from the USA. Accessions were evaluated with 21 207
      restriction site-associated DNA sequencing single nucleotide polymorphism (SNP)
      markers, 424 GoldenGate SNPs and ten plastid microsatellite markers. KEY RESULTS:
      Six genetic clusters of Msi from geographically distinct regions in Asia were
      identified. Genetic data indicated that (1) south-eastern China was the origin of
      Msi populations found in temperate eastern Asia, which is consistent with this
      area probably having been a refugium during the last glacial maximum (LGM); (2)
      Msi migrated directly from south-eastern China to Japan before migrating to the
      same latitudes in China and Korea, which is consistent with the known sequence of
      warming post-LGM; (3) ornamental Msi cultivars were derived from the southern
      Japan population, and US naturalized populations were derived from a sub-set of
      the ornamental cultivars; and (4) many ornamental cultivars previously described
      as Msi have hybrid ancestry from Msa and Msi, whereas US naturalized populations
      of Msi do not. CONCLUSIONS: Population structure of Msi was driven by patterns of
      warming since the LGM, and secondarily by geographical barriers. This study will
      facilitate germplasm conservation, association analyses and identification of
      potential heterotic groups for the improvement of Miscanthus as a bioenergy crop.

PMID- 24918202
TI  - Metabolic remodeling of white adipose tissue in obesity.
AB  - Adipose tissue metabolism is a critical regulator of adiposity and whole body
      energy expenditure; however, metabolic changes that occur in white adipose tissue
      (WAT) with obesity remain unclear. The purpose of this study was to understand
      the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type
      (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole
      body adiposity, had significantly lower V(O2), V(CO2), and respiratory exchange
      ratios, and demonstrated worsened glucose and insulin tolerance compared with low
      fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino
      acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate
      and malate were elevated, and metabolites that could enter the Krebs cycle via
      anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered
      mitochondrial metabolism. Despite no change in basal oxygen consumption or
      mitochondrial DNA abundance, citrate synthase activity was decreased by more than
      50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet.
      Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After
      12 wk of high-fat diet, the abundance of several proteins in the mitochondrial
      respiratory chain or matrix was diminished. These changes were accompanied by
      increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes
      suggestive of autophagy and mitochondrial remodeling. These studies demonstrate
      coordinated restructuring of metabolism and autophagy that could contribute to
      the hypertrophy and whitening of adipose tissue in obesity.

PMID- 24918204
TI  - Drought tolerance and plasticity in the invasive knapweed Centaurea stoebe s.l.
      (Asteraceae): effect of populations stronger than those of cytotype and range.
AB  - BACKGROUND AND AIMS: Spotted knapweed (Centaurea stoebe s.l., Asteraceae) is
      native to Europe, where it occurs as a diploid (2xEU) and tetraploid cytotype
      (4xEU), but so far only the tetraploid has been reported in the introduced range
      in North America (4xNA). In previous studies, significant range shifts have been
      found towards drier climates in 4xEU compared with 2xEU, and in 4xNA when
      compared with the native range. In addition, 4x plants showed thicker leaves and
      reduced specific leaf area compared with 2x plants, suggesting higher drought
      tolerance in 4x plants. It is thus hypothesized that the 4x cytotype might be
      better pre-adapted to drought than the 2x, and the 4xNA better adapted than the
      4xEU due to post-introduction selection. METHODS: Plants of the three
      geocytotypes (2xEU, 4xEU and 4xNA ), each represented by six populations, were
      subjected to three water treatments over 6 weeks in a greenhouse experiment.
      Plasticity and reaction norms of above- and below-ground biomasses and their
      ratio, survival rate, stomatal conductance and carbon isotope discrimination were
      analysed using linear and generalized linear mixed effect models. KEY RESULTS AND
      CONCLUSIONS: Above-ground and total biomasses of European tetraploids were
      slightly less affected by drought than those of European diploids, and 4xEU
      plants maintained higher levels of stomatal conductance under moderate drought
      than 4xNA plants, thus supporting the pre-adaptation but not the post
      introduction evolution hypothesis. Plasticity indexes for most of the traits were
      generally higher in 2xEU and 4xNA than in 4xEU plants, but these differences were
      not or were only marginally significant. Interestingly, the effect of population
      origin and its interaction with treatment was more important than the effects of
      geocytotype and range. Population means for the control treatment showed several
      significant associations either with latitude or some aspect of climatic data,
      suggesting evolution of local adaptations, especially within the 2xEU and 4xEU
      geocytotypes.

PMID- 24918205
TI  - Modelling the mechanical behaviour of pit membranes in bordered pits with respect
      to cavitation resistance in angiosperms.
AB  - BACKGROUND AND AIMS: Various correlations have been identified between anatomical
      features of bordered pits in angiosperm xylem and vulnerability to cavitation,
      suggesting that the mechanical behaviour of the pits may play a role. Theoretical
      modelling of the membrane behaviour has been undertaken, but it requires input of
      parameters at the nanoscale level. However, to date, no experimental data have
      indicated clearly that pit membranes experience strain at high levels during
      cavitation events. METHODS: Transmission electron microscopy (TEM) was used in
      order to quantify the pit micromorphology of four tree species that show
      contrasting differences in vulnerability to cavitation, namely Sorbus aria,
      Carpinus betulus, Fagus sylvatica and Populus tremula. This allowed anatomical
      characters to be included in a mechanical model that was based on the Kirchhoff
      Love thin plate theory. A mechanistic model was developed that included the
      geometric features of the pits that could be measured, with the purpose of
      evaluating the pit membrane strain that results from a pressure difference being
      applied across the membrane. This approach allowed an assessment to be made of
      the impact of the geometry of a pit on its mechanical behaviour, and provided an
      estimate of the impact on air-seeding resistance. KEY RESULTS: The TEM
      observations showed evidence of residual strains on the pit membranes, thus
      demonstrating that this membrane may experience a large degree of strain during
      cavitation. The mechanical modelling revealed the interspecific variability of
      the strains experienced by the pit membrane, which varied according to the pit
      geometry and the pressure experienced. The modelling output combined with the TEM
      observations suggests that cavitation occurs after the pit membrane has been
      deflected against the pit border. Interspecific variability of the strains
      experienced was correlated with vulnerability to cavitation. Assuming that air
      seeding occurs at a given pit membrane strain, the pressure predicted by the
      model to achieve this mechanical state corresponds to experimental values of
      cavitation sensitivity (P50). CONCLUSIONS: The results provide a functional
      understanding of the importance of pit geometry and pit membrane structure in air
      seeding, and thus in vulnerability to cavitation.

PMID- 24918206
TI  - Aerial and soil seed banks enable populations of an annual species to cope with
      an unpredictable dune ecosystem.
AB  - BACKGROUND AND AIMS: Simultaneous formation of aerial and soil seed banks by a
      species provides a mechanism for population maintenance in unpredictable
      environments. Eolian activity greatly affects growth and regeneration of plants
      in a sand dune system, but we know little about the difference in the
      contributions of these two seed banks to population dynamics in sand dunes.
      METHODS: Seed release, germination, seedling emergence and survival of a desert
      annual, Agriophyllum squarrosum (Chenopodiaceae), inhabiting the Ordos Sandland
      in China, were determined in order to explore the different functions of the
      aerial and soil seed banks. KEY RESULTS: The size of the aerial seed bank was
      higher than that of the soil seed bank throughout the growing season. Seed
      release was positively related to wind velocity. Compared with the soil seed
      bank, seed germination from the aerial seed bank was lower at low temperature
      (5/15  degrees C night/day) but higher in the light. Seedling emergence from the
      soil seed bank was earlier than that from the aerial seed bank. Early-emerged (15
      April-15 May) seedlings died due to frost, but seedlings that emerged during the
      following months survived to reproduce successfully. CONCLUSIONS: The timing of
      seed release and different germination behaviour resulted in a temporal
      heterogeneity of seedling emergence and establishment between the two seed banks.
      The study suggests that a bet-hedging strategy for the two seed banks enables A.
      squarrosum populations to cope successfully with the unpredictable desert
      environment.

PMID- 24918207
TI  - Influencing referral of adolescents and young adults with cancer to sites with
      higher rates of trial enrollment.
AB  - Adolescents and young adults (AYAs) have lower rates of clinical trial enrollment
      than younger or older patients with cancer. Multiple approaches to change policy
      and practice need to be used to improve this statistic. This article examines the
      option of increasing referral to 3 types of centers that are known to have
      relatively higher rates of enrollment of AYAs: pediatric cancer centers, AYA
      oncology programs, and National Cancer Institute-designated cancer centers. There
      are reasonable challenges to changing referral patterns, and more research, as
      well as education of those diagnosing AYAs, is required. 

PMID- 24918208
TI  - Improving enrollment in clinical trials for adolescents with cancer.
AB  - Overall cancer cure rates have risen over the last 30 years. Adolescent and young
      adult (AYA) oncology patients aged 15 to 39 have not shared in these successes as
      an age group, including those who fall into the younger age group of 15 to 19
      years. The reasons for this deficit in survival improvement are manifold, but
      research has shown that an important factor is decreased enrollment in
      therapeutic clinical trials in this population versus younger patients. The
      paucity of adolescents treated in clinical trials is itself the result of several
      elements of the health care landscape in the United States. On the local level,
      these factors include referral patterns and facilities available; on the national
      level, related factors include the number of clinical trials available for this
      age group and health care provider education in the care of these patients. We
      examine the data available that have contributed to this deficit in the United
      States and offer broad strategies to address these shortcomings with the goal of
      improving outcomes in this underserved population. 

PMID- 24918209
TI  - Increasing the number of clinical trials available to adolescents diagnosed with
      cancer.
AB  - Improving access to clinical trials for adolescents with cancer remains an
      important issue for pediatric health care providers. In this brief report, we
      highlight barriers to increasing the number of clinical trials as a mechanism for
      addressing this problem. The challenges discussed include: (1) engaging
      stakeholders to increase funding; (2) increasing cooperation between clinical
      trial cooperative groups; and (3) permitting delivery of novel drugs to
      postpubertal adolescents, in the absence of formal pediatric Phase I evaluation. 

PMID- 24918210
TI  - Regulatory barriers to clinical trial enrollment of adolescent and young adult
      oncology patients.
AB  - Adolescent and young adult (AYA) patients with cancer may face unique challenges
      if they and their families wish to participate in clinical oncology trials.
      Regulatory guidelines and funding requirements put in place to protect patients
      may actually raise barriers to enrollment in clinical trials. Hospital age
      guidelines may need to be readdressed to better suit the needs of AYA patients.
      Finally, the creation of the National Clinical Trials Network will provide new
      opportunities for pediatric and medical oncologists to collaborate in the care of
      AYA patients. 

PMID- 24918211
TI  - Psychosocial barriers and facilitators to clinical trial enrollment and adherence
      for adolescents with cancer.
AB  - Adolescents (aged 15-19 years) have not experienced the same survival gains as
      children and older adults diagnosed with cancer. Poor clinical trial enrollment
      and adherence rates among adolescents may account for some of this disparity.
      Although biological, regulatory, systemic, and practice-related challenges to
      clinical trial enrollment and adherence have been examined, studies of
      psychosocial factors, which can serve as barriers or facilitators to enrollment
      and adherence, are limited. To bring attention to these psychological factors, we
      reviewed existing literature on psychosocial barriers and facilitators that can
      affect an adolescent's decision to enroll and adhere to a clinical trial. We also
      provide potential strategies to address psychosocial factors affecting clinical
      trial accrual and adherence. 

PMID- 24918212
TI  - Clinical trial enrollment among adolescents with cancer: supplement overview.
AB  - BACKGROUND: Survival rates for children with cancer have significantly increased
      over the past 35 years. However, adolescents with cancer aged 15 to 19 years have
      had less progress in survival prolongation compared with younger children, which
      may be due to lower clinical trial enrollment among adolescents with cancer. To
      help address this issue, the Centers for Disease Control and Prevention (CDC)
      convened a series of webinars to identify salient issues and measures to address
      this problem. This supplement is intended to raise awareness about the unique
      challenges of clinical trial enrollment among adolescents with cancer. METHODS:
      The CDC convened a workgroup of researchers and health care providers in the
      field of adolescent and young adult oncology and cancer survivorship to examine
      the barriers and challenges limiting the participation of adolescents in clinical
      trials and to define ways to improve on these concerns. RESULTS: The workgroup
      identified 3 distinct issues affecting clinical trial enrollment among
      adolescents with cancer: (1) many adolescents with cancer are not referred to
      institutions where clinical trials are offered, (2) there are limited numbers of
      clinical trials for adolescents with cancer, and (3) psychosocial barriers impede
      adolescents with cancer from enrolling in clinical trials. CONCLUSIONS:
      Adolescents with cancer have the smallest proportion and least number of patients
      enrolled in clinical trials in pediatric oncology. Successfully addressing this
      challenge requires improving referral to existing clinical trials, addressing
      regulatory barriers to clinical trial enrollment, increasing the number of
      clinical trials for adolescents, and addressing unique psychosocial barriers to
      clinical trial enrollment.

PMID- 24918213
TI  - Treatment setting, clinical trial enrollment, and subsequent outcomes among
      adolescents with cancer: a literature review.
AB  - BACKGROUND: There has been an overall improvement in survival rates for persons
      with cancer over the past 35 years. However, these gains are less prevalent among
      adolescents with cancer aged 15 to 19 years, which may be due to lower clinical
      trial enrollment among adolescents with cancer. METHODS: We conducted a
      literature review to assess current research regarding clinical trial enrollment
      and subsequent outcomes among adolescents with cancer. The search included
      English-language publications that reported original data from January 1985 to
      October 2011. RESULTS: The search identified 539 records. Of these 539 records,
      there were 30 relevant original research articles. Multiple studies reported that
      adolescents with cancer are enrolled in clinical trials at lower rates compared
      with younger children and older adults. Treatment setting, physician type, and
      institution type may all be factors in the low enrollment rate among adolescents.
      Few data focused solely on adolescents, with many studies combining adolescents
      with young adults. The number of available studies related to this topic was
      limited, with significant variability in study design, methods, and outcomes.
      CONCLUSIONS: This literature review suggests that adolescents with cancer are not
      treated at optimal settings and are enrolled in clinical trials at low rates.
      This may lead to inferior treatment and poor subsequent medical and psychosocial
      outcomes. The scarcity in data further validates the need for additional research
      focusing on this population.

PMID- 24918215
TI  - Disparities in early exposure to book sharing within immigrant families.
AB  - OBJECTIVE: This study examined the early developmental context of children in
      immigrant families (CIF), measured by the frequency with which parents share
      books with their children. METHODS: Trends in the frequency with which parents
      report book sharing, defined in this analysis as reading or sharing picture books
      with their young children, were analyzed across immigrant and nonimmigrant
      households by using data from the 2005, 2007, and 2009 California Health
      Interview Survey. Stepwise multivariate logistic regression assessed the
      likelihood that CIF shared books with parents daily. RESULTS: In this study,
      57.5% of parents in immigrant families reported daily book sharing (DBS),
      compared with 75.8% of native-born parents. The lowest percentage of DBS was seen
      in Hispanic families with 2 foreign-born parents (47.1%). When controlling for
      independent variables, CIF with 2 foreign-born parents had the lowest odds of
      sharing books daily (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.54
      0.68). When stratified by race/ethnicity, separate multivariate logistic
      regressions revealed CIF status to be associated with lower odds of DBS for Asian
      (OR: 0.56; 95% CI: 0.38-0.81) and Hispanic CIF (OR: 0.49; 95% CI: 0.42-0.58).
      CONCLUSIONS: There is an association between the lower odds of DBS and parental
      immigrant status, especially for Hispanic and Asian children. This relationship
      holds after controlling for variables thought to explain differences in literacy
      related practices, such as parental education and income. Because book sharing is
      central to children's development of early literacy and language skills, this
      disparity merits further exploration with the aim of informing future
      interventions.

PMID- 24918214
TI  - Understanding and addressing the lack of clinical trial enrollment among
      adolescents with cancer.
AB  - Despite overall improvement in survival, morbidity, and quality of life of US
      patients with cancer, this progress is less prevalent in the population of
      adolescent and young adult patients with cancer, including those between the ages
      of 15 and 19 years. Evidence suggests that participation in clinical trials is
      associated with better survival outcomes among children and adolescents with
      cancer; however, adolescents have lower clinical trial participation rates
      compared with younger age cohorts. To better understand the unique concerns among
      adolescent patients with cancer, the Division of Cancer Prevention and Control at
      the Centers for Disease Control and Prevention convened a workgroup of
      researchers and health care providers in the field of adolescent and young adult
      oncology and cancer survivorship to examine the barriers and challenges limiting
      the participation of adolescents in clinical trials and to define ways to improve
      upon these concerns. This article summarizes the activities of the workgroup and
      their suggestions for enhanced accrual. 

PMID- 24918216
TI  - Elucidating challenges and opportunities in the transition to ICD-10-CM.

PMID- 24918217
TI  - The transition to ICD-10-CM: challenges for pediatric practice.
AB  - BACKGROUND AND OBJECTIVES: Diagnostic codes are used widely within health care
      for billing, quality assessment, and to measure clinical outcomes. The US health
      care system will transition to the International Classification of Diseases, 10th
      Revision, Clinical Modification (ICD-10-CM), in October 2015. Little is known
      about how this transition will affect pediatric practices. The objective of this
      study was to examine how the transition to ICD-10-CM may result in ambiguity of
      clinical information and financial disruption for pediatricians. METHODS: Using a
      statewide data set from Illinois Medicaid specified for pediatricians, 2708
      International Classification of Diseases, Ninth Revision, Clinical Modification,
      diagnosis codes were identified. Diagnosis codes were categorized into 1 of 5
      categories: identity, class-to-subclass, subclass-to-class, convoluted, and no
      translation. The convoluted and high-cost diagnostic codes (n = 636) were
      analyzed for accuracy and categorized into "information loss," "overlapping
      categories," "inconsistent," and "consistent." Finally, reimbursement by Medicaid
      was calculated for each category. RESULTS: Twenty-six percent of pediatric
      diagnosis codes are convoluted, which represents 21% of Illinois Medicaid
      pediatric patient encounters and 16% of reimbursement. The diagnosis codes
      represented by information loss (3.6%), overlapping categories (3.2%), and
      inconsistent (1.2%) represent 8% of Medicaid pediatric reimbursement.
      CONCLUSIONS: The potential for financial disruption and administrative errors
      from 8% of reimbursement diagnosis codes necessitates special attention to these
      codes in preparing for the transition to ICD-10-CM for pediatric practices.

PMID- 24918218
TI  - Reducing malnutrition: time to consider potential links between stunting and
      mycotoxin exposure?

PMID- 24918219
TI  - Electronic cigarettes: the new face of nicotine.

PMID- 24918220
TI  - Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin.
AB  - BACKGROUND: Safety concerns for fluoroquinolones exist from animal studies
      demonstrating cartilage injury in weight-bearing joints, dependent on dose and
      duration of therapy. For children treated with levofloxacin or comparator in
      randomized, prospective, comparative studies for acute otitis media and community
      acquired pneumonia, this 5-year follow-up safety study was designed to assess the
      presence/absence of cartilage injury. METHODS: Children enrolled in treatment
      studies were also enrolled in a 1-year follow-up safety study, which; focused on
      musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol
      defined musculoskeletal disorders, or of concern to the Data Safety and
      Monitoring Committee were requested to enroll in four additional years of follow
      up, the subject of this report. RESULTS: Of the 2233 subjects participating in
      the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and
      83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment
      assessment. From children identified with an MSAE during years 2 through 5
      posttreatment, the number that were "possibly related" to drug therapy was equal
      for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all
      cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years'
      posttreatment, no case was assessed as "likely related" to study drug.
      CONCLUSIONS: With no clinically detectable difference between levofloxacin- and
      comparator-treated children in MSAEs presenting between 1 and 5 years in these
      safety studies, risks of cartilage injury with levofloxacin appear to be
      uncommon, are clinically undetectable during 5 years, or are reversible.

PMID- 24918221
TI  - Baby-MONITOR: a composite indicator of NICU quality.
AB  - BACKGROUND AND OBJECTIVES: NICUs vary in the quality of care delivered to very
      low birth weight (VLBW) infants. NICU performance on 1 measure of quality only
      modestly predicts performance on others. Composite measurement of quality of care
      delivery may provide a more comprehensive assessment of quality. The objective of
      our study was to develop a robust composite indicator of quality of NICU care
      provided to VLBW infants that accurately discriminates performance among NICUs.
      METHODS: We developed a composite indicator, Baby-MONITOR, based on 9 measures of
      quality chosen by a panel of experts. Measures were standardized, equally
      weighted, and averaged. We used the California Perinatal Quality Care
      Collaborative database to perform across-sectional analysis of care given to VLBW
      infants between 2004 and 2010. Performance on the Baby-MONITOR is not an absolute
      marker of quality but indicates overall performance relative to that of the other
      NICUs. We used sensitivity analyses to assess the robustness of the composite
      indicator, by varying assumptions and methods. RESULTS: Our sample included 9023
      VLBW infants in 22 California regional NICUs. We found significant variations
      within and between NICUs on measured components of the Baby-MONITOR. Risk
      adjusted composite scores discriminated performance among this sample of NICUs.
      Sensitivity analysis that included different approaches to normalization,
      weighting, and aggregation of individual measures showed the Baby-MONITOR to be
      robust (r = 0.89-0.99). CONCLUSIONS: The Baby-MONITOR may be a useful tool to
      comprehensively assess the quality of care delivered by NICUs.

PMID- 24918222
TI  - Comparison of rapid cranial MRI to CT for ventricular shunt malfunction.
AB  - OBJECTIVES: To compare the accuracy of rapid cranial magnetic resonance imaging
      (MRI) with that of computed tomography (CT) for diagnosing ventricular shunt
      malfunction. METHODS: We performed a single-center, retrospective cohort study of
      children <=21 years of age who underwent either rapid cranial MRI or cranial CT
      in the emergency department (ED) for evaluation of possible ventricular shunt
      malfunction. Each neuroimaging study was classified as "normal" (unchanged or
      decreased ventricle size) or "abnormal" (increased ventricle size). We classified
      a patient as having a ventricular shunt malfunction if operative revision for
      relief of mechanical causes of altered shunt flow was needed within 72 hours of
      initial ED evaluation. Our primary analysis tested noninferiority of the accuracy
      of rapid cranial MRI to CT for diagnosing shunt malfunction (noninferiority
      margin 10%). RESULTS: We included 698 ED visits for 286 unique patients, with a
      median age at visit of 10.0 years (interquartile range 5.9-15.5 years). Patients
      underwent CT in 336 (48%) or rapid cranial MRI in 362 (52%) of ED visits for
      evaluation of possible shunt malfunction. Patients had operative revision for
      ventricular shunt malfunction in 140 ED visits (20%). The accuracy of rapid
      cranial MRI was not inferior to that of CT scan for diagnosing ventricular shunt
      malfunction (81.8% MRI vs 82.4% CT; risk difference 2.0%; 95% confidence
      interval, -4.2% to 8.2%). CONCLUSIONS: Rapid cranial MRI was not inferior to CT
      for diagnosing ventricular shunt malfunction and offers the advantage of sparing
      a child ionizing radiation exposure.

PMID- 24918223
TI  - Adjustment among area youth after the Boston Marathon bombing and subsequent
      manhunt.
AB  - BACKGROUND: The majority of research on terrorism-exposed youth has examined
      large-scale terrorism with mass casualties. Limited research has examined
      children's reactions to terrorism of the scope of the Boston Marathon bombing.
      Furthermore, the extraordinary postattack interagency manhunt and shelter-in
      place warning made for a truly unprecedented experience in its own right for
      families. Understanding the psychological adjustment of Boston-area youth in the
      aftermath of these events is critical for informing clinical efforts. METHODS:
      Survey of Boston-area parents/caretakers (N = 460) reporting on their child's
      experiences during the attack week, as well as psychosocial functioning in the
      first 6 attack months. RESULTS: There was heterogeneity across youth in attack-
      and manhunt-related experiences and clinical outcomes. The proportion of youth
      with likely attack/manhunt-related posttraumatic stress disorder (PTSD) was
      roughly 6 times higher among Boston Marathon-attending youth than nonattending
      youth. Attack and manhunt experiences each uniquely predicted 9% of PTSD symptom
      variance, with manhunt exposures more robustly associated than attack-related
      exposures with a range of psychosocial outcomes, including emotional symptoms,
      conduct problems, hyperactivity/inattention, and peer problems. One-fifth of
      youth watched >3 hours of televised coverage on the attack day, which was linked
      to PTSD symptoms, conduct problems, and total difficulties. Prosocial behavior
      and positive peer functioning buffered the impact of exposure. CONCLUSIONS:
      Clinical efforts must maintain a broadened focus beyond simply youth present at
      the blasts and must also include youth highly exposed to the intense interagency
      pursuit and manhunt. Continued research is needed to understand the adjustment of
      youth after mass traumas and large-scale manhunts in residential communities.

PMID- 24918224
TI  - Exposure to electronic cigarette television advertisements among youth and young
      adults.
AB  - BACKGROUND AND OBJECTIVE: Currently, the US Food and Drug Administration does not
      regulate electronic cigarette (e-cigarette) marketing unless it is advertised as
      a smoking cessation aid. To date, the extent to which youth and young adults are
      exposed to e-cigarette television advertisements is unknown. The objective of
      this study was to analyze trends in youth and young adult exposure to e-cigarette
      television advertisements in the United States. METHODS: Nielsen data on
      television household audiences' exposure to e-cigarette advertising across US
      markets were examined by calendar quarter, year, and sponsor. RESULTS: Youth
      exposure to television e-cigarette advertisements, measured by target rating
      points, increased 256% from 2011 to 2013. Young adult exposure increased 321%
      over the same period. More than 76% of all youth e-cigarette advertising exposure
      occurred on cable networks and was driven primarily by an advertising campaign
      for 1 e-cigarette brand. CONCLUSIONS: E-cigarette companies currently advertise
      their products to a broad audience that includes 24 million youth. The dramatic
      increase in youth and young adult television exposure between 2011 and 2013 was
      driven primarily by a large advertising campaign on national cable networks. In
      the absence of evidence-based public health messaging, the current e-cigarette
      television advertising may be promoting beliefs and behaviors that pose harm to
      the public health. If current trends in e-cigarette television advertising
      continue, awareness and use of e-cigarettes are likely to increase among youth
      and young adults.

PMID- 24918225
TI  - Eruptive xanthomas masquerading as molluscum contagiosum.
AB  - Eruptive xanthomas are cutaneous manifestations of hyperlipidemias in which
      lipids accumulate in large foam cells within the skin. They classically present
      as crops of 1- to 4-mm yellow-orange papules and are often associated with
      extreme hypertriglyceridemia. We describe a 12-year-old boy with autism who was
      thought to have widespread molluscum contagiosum for a year before dermatologic
      consultation was obtained. Recognition of eruptive xanthomas led to the discovery
      of massive hypertriglyceridemia (serum triglycerides 6853 mg/dL) and diabetes
      mellitus. Through medical intervention, including insulin and fenofibrate
      therapy, and dietary modification with weight loss, the xanthomas cleared during
      the subsequent months, and his serum triglyceride levels nearly normalized. 

PMID- 24918227
TI  - Was Sarah Murnaghan treated justly?
AB  - Lung transplantation is a potentially life-saving procedure for patients with
      irreversible lung failure. Five-year survival rates after lung transplantation
      are >50% for children and young adults. But there are not enough lungs to save
      everyone who could benefit. In 2005, the United Network for Organ Sharing
      developed a scoring system to prioritize patients for transplantation. That
      system considered transplant urgency as well as time on the waiting list and the
      likelihood that the patient would benefit from the transplant. At the time, there
      were so few pediatric lung transplants that the data that were used to develop
      the Lung Allocation Score were inadequate to analyze and prioritize children, so
      they were left out of the Lung Allocation Score system. In 2013, the family of a
      10-year-old challenged this system, claiming that it was unjust to children. In
      the article, we asked experts in health policy, bioethics, and transplantation to
      discuss the issues in the Murnaghan case. 

PMID- 24918226
TI  - Parental injury and psychological health of children.
AB  - OBJECTIVE: To determine how parental injury affects the psychological health and
      functioning of injured as well as uninjured children. METHODS: We recruited 175
      parent-child dyads treated at a regional trauma center in 4 groups: parent and
      child both injured in the same event, child-only injured, parent-only injured,
      and neither parent nor child met criteria for significant injury. The preinjury
      health and functioning of parents and children were assessed with follow-up at 5
      and 12 months. RESULTS: Parents who were injured themselves showed higher levels
      of impairment in activities of daily living, quality of life, and depression at
      both follow-up assessments than parents who were not injured. Children in dyads
      with both parent and child injured had the highest proportion of posttraumatic
      stress disorder (PTSD) symptoms at both 5 and 12 months. In addition, children
      with an injured parent but who were not injured themselves were more likely to
      report PTSD symptoms at 5 months. CONCLUSIONS: There were bidirectional effects
      of parental and child injury on the outcomes of each other. Injuries to the
      parent negatively affected the health-related quality of life of the injured
      children, over and above the effect of the injury itself on the child. Of great
      concern is the effect of parental injury on risk of stress and PTSD among
      uninjured children in the home.

PMID- 24918233
TI  - Iain Campbell - a personal recollection.

PMID- 24918234
TI  - Role of nutraceuticals in dementia care.
AB  - With an increase in the number of patients diagnosed with Alzheimer's disease, it
      is not surprising that there is a consistent increase in use of nutraceuticals
      and other over-the-counter medications to combat memory complaints and ideally
      treat dementia. Throughout this review article, the authors highlight recent
      literature updates on B vitamins, vitamin D, vitamin E, omega-3 fatty acids, and
      gingko biloba. Similar to any other medication, it is imperative to evaluate the
      risks and benefits in older patients, especially in light of comorbidities and
      existing medications.

PMID- 24918235
TI  - [Oncogenes, tumor suppressor genes, and aneuploidy: the sum of the nuances].

PMID- 24918236
TI  - [The epigenetic mechanisms at work in pediatric gliomas].

PMID- 24918237
TI  - Retraction statement: The spectrum of morphology in non-neoplastic prostate
      including cancer mimics.

PMID- 24918238
TI  - Home lighting before usual bedtime impacts circadian timing: a field study.
AB  - Laboratory studies suggest that evening light before bedtime can suppress
      melatonin. Here, we measured the range of evening light intensity people can
      generate with their household lights, and for the first time determined if
      varying home light before usual bedtime can shift circadian phase. This was a 3
      week study with two counterbalanced conditions separated by a 5-day break. In a
      dim week, eight healthy subjects minimized their home light exposure from 4 h
      before habitual bedtime until a self-selected bedtime. In a bright week, the
      subjects maximized their home lighting for the same time. The dim light melatonin
      onset (DLMO) was assessed after each week. On average subjects maximized their
      lights to approximately 65 lux and minimized their lights to approximately 3 lux.
      Wrist actigraphy indicated that subjects went to bed slightly later when lights
      were maximized (average 14 min later, P = 0.05), but wake time did not change.
      Every subject had a later DLMO after the week of maximum versus minimum light
      exposure (average 1:03 h later, P < 0.001). These results demonstrate that the
      light intensity people can generate at home in the few hours before habitual
      bedtime can alter circadian timing. People should reduce their evening light
      exposure to lessen circadian misalignment.

PMID- 24918239
TI  - Early diagnosis of colorectal cancer in rats with DMH induced carcinogenesis by
      means of urine autofluorescence analysis.
AB  - Cancer is one of the most highlighted topics of current research. Early detection
      of this disease allows more effective therapy, hence higher chance of cure.
      Application of fluorescence spectral techniques into oncological diagnostic is
      one of the potential alternatives. Chemically induced carcinogenesis in rats is
      widely used model for exploration of various aspects of colorectal cancer. This
      study shows value of discriminate analysis of urine fluorescent fingerprint
      between healthy control group of rats and those with dimethylhydrazine induced
      early lesions of colorectal cancer. Using fluorescence spectroscopy, significant
      difference (P < 0.05) between both of group was achieved.

PMID- 24918240
TI  - Heartsick: psychiatric and inflammatory implications of cerebromicrovascular
      disease.
AB  - BACKGROUND: Cerebromicrovascular disease (CMVD) strikes 87% of the population
      older than 65 years and is linked to an increased risk of ischemic stroke,
      depression, cognitive impairment, and Alzheimer's disease. Despite the wealth of
      knowledge on the consequences to the body stemming from poor vascular health,
      little focus has been placed on the consequences to the brain. DESIGN: In this
      review, we present the preclinical and clinical evidence that supports the role
      of CMVD in behavioral dysfunction, argues for a clinical need for better
      recognition of the vascular depression phenotype, and calls for a more
      integrative translational approach to CMVD. RESULTS AND CONCLUSIONS: Although the
      concept of cerebrovascular-induced behavioral change has existed for over 100
      years, the difficulty of diagnosis, the slow progression of CMVD, and the lack of
      causative data have led to an underestimation of the patient population and poor
      treatment strategies. Preclinical studies have focused on the use of microsphere
      embolic models and vascular inflammation models to assess the mechanisms of, and
      treatment options for, CMVD. Though preclinical models provide support for
      correlative data collected in the clinic, translational reciprocity has not been
      established. The lack of clinical appreciation for the role of cerebrovascular
      health in brain function may result in missed diagnoses and inadequate treatment
      of underlying cardiovascular disease. Enhanced recognition of symptoms and
      disease presentation will allow for earlier prevention, detection, and
      identification of novel targets for drug development and other intervention
      strategies.

PMID- 24918241
TI  - Cumulative sojourn time in longitudinal  studies: a sequential imputation method 
      to handle missing health state data due  to dropout.
AB  - Missing data are ubiquitous in longitudinal studies. In this paper, we propose an
      imputation procedure to handle dropouts in longitudinal studies. By taking
      advantage of the monotone missing pattern resulting from dropouts, our imputation
      procedure can be carried out sequentially, which substantially reduces the
      computation complexity. In addition, at each step of the sequential imputation,
      we set up a model selection mechanism that chooses between a parametric model and
      a nonparametric model to impute eachmissing observation. Unlike usual model
      selection procedures that aim at finding a single model fitting the entire data
      set well, our model selection procedure is customized to find a suitable model
      for the prediction of each missing observation.

PMID- 24918242
TI  - Functional analysis of glaucoma data.
AB  - We refer glaucoma to a category of eye disorders often associated with a
      dangerous buildup of intraocular pressure (IOP), which can damage the eyes' optic
      nerve that transmits visual information to the brain. Because IOP changes over
      time, it is a function of time, and it is an advantage that we analyze the
      phenomenon using functional data analysis. In this paper, we treat the data
      related to the IOP of 35 patients with right eye glaucoma, collected in Rasul-e
      Akram Hospital at Tehran, Iran, over the years 2007-2011. We shall explore the
      structure of the data in search of the features that describe them, and find the
      characteristics that give a comprehensible presentation of the structure of the
      variability in the data.We extract patterns of variation in the data by using a
      generalization of the smoothed functional principal component analysis to obtain
      the main factors causing glaucoma and then determine their importance. We also
      explore the correlation patterns between the IOP of right and left eyes, and then
      model the left eye IOP of the glaucoma patients at each time on the basis of
      their right eye IOP in a previous interval of time.We can use the model to
      predict the values of the former variable by using the latter one in a previous
      time interval.

PMID- 24918244
TI  - [Acute obstructive crisis ? Non-invasive ventilation ? Weaning long-term
      ventilation ].

PMID- 24918243
TI  - [AAD 2014 -- every patient is unique and requires individual treatment].

PMID- 24918245
TI  - Multiple imputation for  high-dimensional mixed incomplete  continuous and binary
      data.
AB  - It is common in applied research to have large numbers of variables measured on a
      modest number of cases. Even with low rates of missingness of individual
      variables, such data sets can have a large number of incomplete cases with a mix
      of data types. Here, we propose a new joint modeling approach to address the high
      dimensional incomplete data with a mix of continuous and binary data.
      Specifically, we propose a multivariate normal model encompassing both continuous
      variables and latent variables corresponding to binary variables. We apply a
      parameter-extended Metropolis-Hastings algorithm to generate the covariance
      matrix of a mixture of continuous and binary variables. We also introduce prior
      distribution families for unstructured covariance matrices to reduce the
      dimension of the parameter space. In several simulation settings, the method is
      compared with available-case analysis, a rounding method, and a sequential
      regression method.

PMID- 24918246
TI  - An approach for modelling multiple  correlated outcomes in a network of 
      interventions using odds ratios.
AB  - A multivariate meta-analysis of two or more correlated outcomes is expected to
      improve precision compared with a series of independent, univariate meta-analyses
      especially when there are studies reporting some but not all outcomes.
      Multivariate meta-analysis requires estimates of the within-study correlations,
      which are seldom available. Existing methods for analysing multiple outcomes
      simultaneously are limited to pairwise treatment comparisons. We propose a model
      for a joint, simultaneous synthesis of multiple dichotomous outcomes in a network
      of interventions and introduce a simple way to elicit expert opinion for the
      within-study correlations by utilizing a set of conditional probability
      parameters. We implement our multiple-outcomes network meta-analysis model within
      a Bayesian framework, which allows incorporation of expert information. As an
      example, we analyse two correlated dichotomous outcomes, response to the
      treatment and dropout rate, in a network of pharmacological interventions for
      acute mania. The produced estimates have narrower confidence intervals compared
      with the simple network meta-analysis. We conclude that the proposed model and
      the suggested prior elicitation method for correlations constitute a useful
      framework for performing network meta-analysis for multiple outcomes.

PMID- 24918247
TI  - Reply to De Coster et al.: Exploring the complexity of ecosystem-human health
      relationships.

PMID- 24918249
TI  - Report and session summary from the 18th World Congress on Disaster and Emergency
      Medicine.

PMID- 24918248
TI  - Reply to Deighton et al.: Neuronal activity regulates distinct antioxidant
      pathways in neurons and astrocytes.

PMID- 24918250
TI  - Biomechanical fatigue analysis of an advanced new  carbon fiber/flax/epoxy plate
      for bone fracture repair  using conventional fatigue tests and thermography.
AB  - The current study is part of an ongoing research program to develop an advanced
      new carbon fiber/flax/epoxy (CF/flax/epoxy) hybrid composite with a "sandwich
      structure" as a substitute for metallic materials for orthopedic long bone
      fracture plate applications. The purpose of this study was to assess the fatigue
      properties of this composite, since cyclic loading is one of the main types of
      loads carried by a femur fracture plate during normal daily activities.
      Conventional fatigue testing, thermographic analysis, and scanning electron
      microscopy (SEM) were used to analyze the damage progress that occurred during
      fatigue loading. Fatigue strength obtained using thermography analysis (51% of
      ultimate tensile strength) was confirmed using the conventional fatigue test (50
      55% of ultimate tensile strength). The dynamic modulus (E*) was found to stay
      almost constant at 47 GPa versus the number of cycles, which can be related to
      the contribution of both flax/epoxy and CF/epoxy laminae to the stiffness of the
      composite. SEM images showed solid bonding at the CF/epoxy and flax/epoxy
      laminae, with a crack density of only 0.48% for the plate loaded for 2 million
      cycles. The current composite plate showed much higher fatigue strength than the
      main loads experienced by a typical patient during cyclic activities; thus, it
      may be a potential candidate for bone fracture plate applications. Moreover, the
      fatigue strength from thermographic analysis was the same as that obtained by the
      conventional fatigue tests, thus demonstrating its potential use as an alternate
      tool to rapidly evaluate fatigue strength of composite biomaterials.

PMID- 24918251
TI  - Tribute to Professor Gilbert Huault (1932-2013).

PMID- 24918252
TI  - Reversible symmetric nonexpansive convolution: an effective image boundary
      processing for M-channel lifting-based linear-phase filter banks.
AB  - We present an effective image boundary processing for M-channel (M ? IN, M >= 2)
      lifting-based linear-phase filter banks that are applied to unified lossy and
      lossless image compression (coding), i.e., lossy-to-lossless image coding. The
      reversible symmetric extension we propose is achieved by manipulating building
      blocks on the image boundary and reawakening the symmetry of each building block
      that has been lost due to rounding error on each lifting step. In addition,
      complexity is reduced by extending nonexpansive convolution, called reversible
      symmetric nonexpansive convolution, because the number of input signals does not
      even temporarily increase. Our method not only achieves reversible boundary
      processing, but also is comparable with irreversible symmetric extension in lossy
      image coding and outperformed periodic extension in lossy-to-lossless image
      coding.

PMID- 24918253
TI  - The mechanisms leading to emergence and spread of zoonotic diseases. Preface.

PMID- 24918254
TI  - Global health security.

PMID- 24918255
TI  - Do your staff feel safe to speak out?

PMID- 24918256
TI  - Rekindle your curiosity.

PMID- 24918257
TI  - Patient collections: cleaning up the mess. As payment moves to point of service,
      inefficiency abounds.

PMID- 24918259
TI  - Simple, sensitive, and quantitative electrochemical detection method for paper
      analytical devices.
AB  - We report a new type of paper analytical device that provides quantitative
      electrochemical output and detects concentrations as low as 767 fM. The model
      analyte is labeled with silver nanoparticles (AgNPs), which provide 250,000-fold
      amplification. AgNPs eliminate the need for enzymatic amplification, thereby
      improving device stability and response time. The use of magnetic beads to
      preconcentrate the AgNPs at the detection electrode further improves sensitivity.
      Response time is improved by incorporation of a hollow channel, which increases
      the flow rate in the device by a factor of 7 and facilitates the use of magnetic
      beads. A key reaction necessary for label detection is made possible by the
      presence of a slip layer, a fluidic switch that can be actuated by manually
      slipping a piece of paper. The design of the device is versatile and should be
      useful for detection of proteins, nucleic acids, and microbes.

PMID- 24918258
TI  - Molecular recognition of methyl alpha-D-mannopyranoside by antifreeze
      (glyco)proteins.
AB  - Antifreeze proteins and glycoproteins [AF(G)Ps] have been well-known for more
      than three decades for their ability to inhibit the growth and recrystallization
      of ice through binding to specific ice crystal faces, and they show remarkable
      structural compatibility with specific ice crystal faces. Here, we show that the
      crystal growth faces of methyl alpha-D-mannopyranoside (MDM), a representative
      pyranose sugar, also show noteworthy structural compatibility with the known
      periodicities of AF(G)Ps. We selected fish AFGPs (AFGP8, AFGP1-5), and a beetle
      AFP (DAFP1) with increasing antifreeze activity as potential additives for
      controlling MDM crystal growth. Similar to their effects on ice growth, the
      AF(G)Ps can inhibit MDM crystal growth and recrystallization, and more
      significantly, the effectiveness for the AF(G)Ps are well correlated with their
      antifreeze activity. MDM crystals grown in the presence of AF(G)Ps are smaller
      and have better defined shapes and are of higher quality as indicated by single
      crystal X-ray diffraction and polarized microscopy than control crystals, but no
      new polymorphs of MDM were identified by single crystal X-ray diffraction, solid
      state NMR, and attenuated total reflectance infrared spectroscopy. The observed
      changes in the average sizes of the MDM crystals can be related to the changes in
      the number of the MDM nuclei in the presence of the AF(G)Ps. The critical free
      energy change differences of the MDM nucleation in the absence and presence of
      the additives were calculated. These values are close to those of the ice
      nucleation in the presence of AF(G)Ps suggesting similar interactions are
      involved in the molecular recognition of MDM by the AF(G)Ps. To our knowledge
      this is the first report where AF(G)Ps have been used to control crystal growth
      of carbohydrates and on AFGPs controlling non-ice-like crystals. Our finding
      suggests MDM might be a possible alternative to ice for studying the detailed
      mechanism of AF(G)P-crystal interactions. The relationships between AF(G)Ps and
      carbohydrate binding proteins are also discussed. The structural compatibility
      between AF(G)Ps and growing crystal faces demonstrated herein adds to the
      repertoire of molecular recognition by AF(G)Ps, which may have potential
      applications in the sugar, food, pharmaceutical, and materials industries.

PMID- 24918260
TI  - Selective deposition of Ru nanoparticles on TiSi2 nanonet and its utilization for
      Li2O2 formation and decomposition.
AB  - The Li-O2 battery promises high capacity to meet the need for electrochemical
      energy storage applications. Successful development of the technology hinges on
      the availability of stable cathodes. The reactivity exhibited by a carbon support
      compromises the cyclability of Li-O2 operation. A noncarbon cathode support has
      therefore become a necessity. Using a TiSi2 nanonet as a high surface area,
      conductive support, we obtained a new noncarbon cathode material that corrects
      the deficiency. To enable oxygen reduction and evolution, Ru nanoparticles were
      deposited by atomic layer deposition onto TiSi2 nanonets. A surprising site
      selective growth whereupon Ru nanoparticles only deposit onto the b planes of
      TiSi2 was observed. DFT calculations show that the selectivity is a result of
      different interface energetics. The resulting heteronanostructure proves to be a
      highly effective cathode material. It enables Li-O2 test cells that can be
      recharged more than 100 cycles with average round-trip efficiencies >70%. 

PMID- 24918261
TI  - Cinnamic anilides as new mitochondrial permeability transition pore inhibitors
      endowed with ischemia-reperfusion injury protective effect in vivo.
AB  - In this account, we report the development of a series of substituted cinnamic
      anilides that represents a novel class of mitochondrial permeability transition
      pore (mPTP) inhibitors. Initial class expansion led to the establishment of the
      basic structural requirements for activity and to the identification of
      derivatives with inhibitory potency higher than that of the standard inhibitor
      cyclosporine-A (CsA). These compounds can inhibit mPTP opening in response to
      several stimuli including calcium overload, oxidative stress, and thiol cross
      linkers. The activity of the cinnamic anilide mPTP inhibitors turned out to be
      additive with that of CsA, suggesting for these inhibitors a molecular target
      different from cyclophylin-D. In vitro and in vivo data are presented for (E)-3
      (4-fluoro-3-hydroxy-phenyl)-N-naphthalen-1-yl-acrylamide 22, one of the most
      interesting compounds in this series, able to attenuate opening of the mPTP and
      limit reperfusion injury in a rabbit model of acute myocardial infarction. 

PMID- 24918262
TI  - Modification of body composition and metabolism during oral contraceptives
      containing non-androgenic progestins in association with estradiol or ethinyl
      estradiol.
AB  - AIM: To observe the influence on metabolism and body composition of two oral
      contraceptives containing non-androgenic progestins in association with estradiol
      or ethinyl estradiol (EE). STUDY DESIGN: Women on hormonal contraception with
      estradiol valerate (E2V)/dienogest (DNG) in a quadriphasic regimen (n = 16) or 30
      MUg EE/2 mg chlormadinone acetate (CMA) (n = 16) in a monophasic regimen were
      evaluated at the third cycle for modifications in lipoproteins, apoproteins and
      homeostatic model assessment for insulin resistance (HOMA-IR), and at the sixth
      cycle for body composition and the markers of bone turnover osteocalcin and C
      telopeptide X. RESULTS: During E2V/DNG lipoprotein, apoproteins and HOMA-IR
      remained stable. During EE/CMA, total-cholesterol (p = 0.003), high-density
      lipoprotein (HDL)-cholesterol (p = 0.001), triglycerides (p = 0.003) Apoprotein
      A1 (Apo-A1; p = 0.001) and Apo B (p = 0.04) increased, low-density
      lipoprotein/HDL (p = 0.039) decreased and total-cholesterol/HDL and Apoprotein
      B/Apo-A1 ratio did not vary. HOMA-IR slightly increased from 1.33 +/- 0.87 to
      1.95 +/- 0.88 (p = 0.005). There was a reduction of markers of bone metabolism in
      both groups with no modification of body composition. CONCLUSIONS: Administration
      of E2V/DNG does not influence lipid and glucose metabolism, while mixed effect
      are exerted by EE/CMA. Both preparations reduce bone metabolism without
      influencing short-term effect on body composition.

PMID- 24918263
TI  - Fine tuning of fluorene-based dye structures for high-efficiency p-type dye
      sensitized solar cells.
AB  - We report on an experimental study of three organic push-pull dyes (coded as zzx
      op1, zzx-op1-2, and zzx-op1-3) featuring one, two, and three fluorene units as
      spacers between donors and acceptors for p-type dye-sensitized solar cells (p
      DSSC). The results show increasing the number of spacer units leads to obvious
      increases of the absorption intensity between 300 nm and 420 nm, a subtle
      increase in hole driving force, and almost the same hole injection rate from dyes
      to NiO nanoparticles. Under optimized conditions, the zzx-op1-2 dye with two
      fluorene spacer units outperforms other two dyes in p-DSSC. It exhibits an
      unprecedented photocurrent density of 7.57 mA cm(-2) under full sun illumination
      (simulated AM 1.5G light illumination, 100 mW cm(-2)) when the I(-)/I3(-) redox
      couple and commercial NiO nanoparticles were used as an electrolyte and a
      semiconductor, respectively. The cells exhibited excellent long-term stability.
      Theoretical calculations, impedance spectroscopy, and transient photovoltage
      decay measurements reveal that the zzx-op1-2 exhibits lower photocurrent losses,
      longer hole lifetime, and higher photogenerated hole density than zzx-op1 and zzx
      op1-3. A dye packing model was proposed to reveal the impact of dye aggregation
      on the overall photovoltaic performance. Our results suggest that the structural
      engineering of organic dyes is important to enhance the photovoltaic performance
      of p-DSSC. 

PMID- 24918264
TI  - Construction of a zinc porphyrin-fullerene-derivative based nonenzymatic
      electrochemical sensor for sensitive sensing of hydrogen peroxide and nitrite.
AB  - Enzymatic sensors possess high selectivity but suffer from some limitations such
      as instability, complicated modified procedure, and critical environmental
      factors, which stimulate the development of more sensitive and stable
      nonenzymatic electrochemical sensors. Herein, a novel nonenzymatic
      electrochemical sensor is proposed based on a new zinc porphyrin-fullerene (C60)
      derivative (ZnP-C60), which was designed and synthesized according to the
      conformational calculations and the electronic structures of two typical ZnP-C60
      derivatives of para-ZnP-C60 (ZnP(p)-C60) and ortho-ZnP-C60 (ZnP(o)-C60). The two
      derivatives were first investigated by density functional theory (DFT) and ZnP(p)
      C60 with a bent conformation was verified to possess a smaller energy gap and
      better electron-transport ability. Then ZnP(p)-C60 was entrapped in
      tetraoctylammonium bromide (TOAB) film and modified on glassy carbon electrode
      (TOAB/ZnP(p)-C60/GCE). The TOAB/ZnP(p)-C60/GCE showed four well-defined quasi
      reversible redox couples with extremely fast direct electron transfer and
      excellent nonenzymatic sensing ability. The electrocatalytic reduction of H2O2
      showed a wide linear range from 0.035 to 3.40 mM, with a high sensitivity of
      215.6 MUA mM(-1) and a limit of detection (LOD) as low as 0.81 MUM. The
      electrocatalytic oxidation of nitrite showed a linear range from 2.0 MUM to 0.164
      mM, with a sensitivity of 249.9 MUA mM(-1) and a LOD down to 1.44 MUM. Moreover,
      the TOAB/ZnP(p)-C60/GCE showed excellent stability and reproducibility, and good
      testing recoveries for analysis of the nitrite levels of river water and
      rainwater. The ZnP(p)-C60 can be used as a novel material for the fabrication of
      nonenzymatic electrochemical sensors.

PMID- 24918265
TI  - Statistical Approaches to Assess the Association between Phenolic Compounds and
      the in vitro Antioxidant Activity of Camellia sinensis and Ilex paraguariensis
      Teas.
AB  - Tea presents a diverse phenolic composition which is responsible for its alleged
      biological activities, including the in vivo and in vitro antioxidant capacity.
      It is very usual to find researches applying statistical methods, such as
      analysis of variances (ANOVA) and linear Pearson correlation coefficients to
      analyze the strength of correlation between phenolic composition and the in vitro
      antioxidant activity of teas from Camellia sinensis (green, black, white, oolong,
      red, and yellow teas) and Ilex paraguariensis (Yerba-mate), which are the most
      produced and consumed types of teas. However, evidence has shown that these
      approaches are not as suitable as multivariate statistical methods once they do
      not depict nor show association among all results and variables simultaneously,
      making it difficult to understand clearly the data structure and patterns. Then,
      the objective of this work is to review and explain some univariate/bivariate and
      multivariate statistical techniques used to assess the association between
      phenolic compounds and the in vitro antioxidant activity of green, white, black,
      red, yellow, oolong and Yerba-mate teas. Moreover, this paper provides an
      overview on some assays used to estimate the in vitro antioxidant capacity of
      teas. 

PMID- 24918266
TI  - Sexual sensation seeking in Spanish young men and women with different sexual
      orientations.
AB  - This study analyzes the relation of sexual orientation and gender to sexual
      sensation seeking. Participants were 382 individuals (200 men, 182 women) between
      17 and 29 years old who completed the Sexual Sensation Seeking Scale. Of the 382
      participants, 52.46% self-reported heterosexual orientation, and 47.64% self
      reported homosexual orientation. The results showed differences with Sexual
      Sensation Seeking being more frequent among heterosexuals and men. There were no
      differences between heterosexual and homosexual men. Heterosexual women had
      higher sexual sensation seeking scores than did homosexual women. These results
      and their possible implications for the effective development of prevention and
      intervention programs in affective-sexual education are discussed. 

PMID- 24918267
TI  - Prevalence and intensity of nematode parasites in Wisconsin ermine.
AB  - In the midwestern United States, ermine ( Mustela erminea ) are economically
      important because they are legally harvested for pelts. Information on parasites
      of ermine is lacking, and the effects that nematode parasites have on body
      condition of ermine hosts are unknown. We identified Skrjabingylus nasicola and
      Filaroides martis in ermine trapped from 2007 to 2013 from 6 counties in
      Wisconsin. Small mammals, commonly consumed by ermine, serve as paratenic hosts
      for both parasites. Our goal was to identify how age and sex of ermine, along
      with year, influence nematode parasitism. We also investigated how infection
      affected body condition for male and female ermine using body mass standardized
      by length as an index of body condition. We commonly found S. nasicola and F.
      martis in male and female ermine, but both prevalence and intensity of infection
      were higher for males. Relative to juveniles (<1 yr), adult (>1 yr) male ermine
      did not exhibit significantly higher intensity or prevalence of either parasite.
      We found that body condition was not compromised by infection for either sex, and
      intensity of S. nasicola and prevalence of F. martis were highest during the 2010
      2011 trapping season. Of the 6 yr studied, precipitation was highest during the
      summer before the 2010-2011 season, and increased precipitation can cause
      increases in populations of gastropod intermediate hosts. We think that several
      distinct natural history components, namely, mating structure, diet, and
      metabolic rate, influence nematode parasitism in ermine. 

PMID- 24918269
TI  - Telemedicine and e-health in disaster response.

PMID- 24918268
TI  - Passive strain-induced matrix synthesis and organization in shape-specific,
      cartilaginous neotissues.
AB  - Tissue-engineered musculoskeletal soft tissues typically lack the appropriate
      mechanical robustness of their native counterparts, hindering their clinical
      applicability. With structure and function being intimately linked, efforts to
      capture the anatomical shape and matrix organization of native tissues are
      imperative to engineer functionally robust and anisotropic tissues capable of
      withstanding the biomechanically complex in vivo joint environment. The present
      study sought to tailor the use of passive axial compressive loading to drive
      matrix synthesis and reorganization within self-assembled, shape-specific
      fibrocartilaginous constructs, with the goal of developing functionally
      anisotropic neotissues. Specifically, shape-specific fibrocartilaginous
      neotissues were subjected to 0, 0.01, 0.05, or 0.1 N axial loads early during
      tissue culture. Results found the 0.1-N load to significantly increase both
      collagen and glycosaminoglycan synthesis by 27% and 67%, respectively, and to
      concurrently reorganize the matrix by promoting greater matrix alignment,
      compaction, and collagen crosslinking compared with all other loading levels.
      These structural enhancements translated into improved functional properties,
      with the 0.1-N load significantly increasing both the relaxation modulus and
      Young's modulus by 96% and 255%, respectively, over controls. Finite element
      analysis further revealed the 0.1-N uniaxial load to induce multiaxial tensile
      and compressive strain gradients within the shape-specific neotissues, with
      maxima of 10.1%, 18.3%, and -21.8% in the XX-, YY-, and ZZ-directions,
      respectively. This indicates that strains created in different directions in
      response to a single axis load drove the observed anisotropic functional
      properties. Together, results of this study suggest that strain thresholds exist
      within each axis to promote matrix synthesis, alignment, and compaction within
      the shape-specific neotissues. Tailoring of passive axial loading, thus, presents
      as a simple, yet effective way to drive in vitro matrix development in shape
      specific neotissues toward more closely achieving native structural and
      functional properties. 

PMID- 24918271
TI  - Accuracy evaluation of a new real-time continuous glucose monitoring algorithm in
      hypoglycemia.
AB  - BACKGROUND: The purpose of this study was to evaluate the performance of a new
      continuous glucose monitoring (CGM) calibration algorithm and to compare it with
      the Guardian((r)) REAL-Time (RT) (Medtronic Diabetes, Northridge, CA) calibration
      algorithm in hypoglycemia. SUBJECTS AND METHODS: CGM data were obtained from 10
      type 1 diabetes patients undergoing insulin-induced hypoglycemia. Data were
      obtained in two separate sessions using the Guardian RT CGM device. Data from the
      same CGM sensor were calibrated by two different algorithms: the Guardian RT
      algorithm and a new calibration algorithm. The accuracy of the two algorithms was
      compared using four performance metrics. RESULTS: The median (mean) of absolute
      relative deviation in the whole range of plasma glucose was 20.2% (32.1%) for the
      Guardian RT calibration and 17.4% (25.9%) for the new calibration algorithm. The
      mean (SD) sample-based sensitivity for the hypoglycemic threshold of 70 mg/dL was
      31% (33%) for the Guardian RT algorithm and 70% (33%) for the new algorithm. The
      mean (SD) sample-based specificity at the same hypoglycemic threshold was 95%
      (8%) for the Guardian RT algorithm and 90% (16%) for the new calibration
      algorithm. The sensitivity of the event-based hypoglycemia detection for the
      hypoglycemic threshold of 70 mg/dL was 61% for the Guardian RT calibration and
      89% for the new calibration algorithm. Application of the new calibration caused
      one false-positive instance for the event-based hypoglycemia detection, whereas
      the Guardian RT caused no false-positive instances. The overestimation of plasma
      glucose by CGM was corrected from 33.2 mg/dL in the Guardian RT algorithm to 21.9
      mg/dL in the new calibration algorithm. CONCLUSIONS: The results suggest that the
      new algorithm may reduce the inaccuracy of Guardian RT CGM system within the
      hypoglycemic range; however, data from a larger number of patients are required
      to compare the clinical reliability of the two algorithms.

PMID- 24918270
TI  - Asbestos-induced pulmonary fibrosis is augmented in 8-oxoguanine DNA glycosylase
      knockout mice.
AB  - Asbestos causes asbestosis and malignancies by mechanisms that are not fully
      established. Alveolar epithelial cell (AEC) injury and repair are crucial
      determinants of the fibrogenic potential of noxious agents such as asbestos. We
      previously showed that mitochondrial reactive oxygen species mediate asbestos
      induced AEC intrinsic apoptosis and that mitochondrial human 8-oxoguanine-DNA
      glycosylase 1 (OGG1), a DNA repair enzyme, prevents oxidant-induced AEC
      apoptosis. We reasoned that OGG1 deficiency augments asbestos-induced pulmonary
      fibrosis. Compared with intratracheal instillation of PBS (50 MUl) or titanium
      dioxide (100 MUg/50 MUl), crocidolite or Libby amphibole asbestos (100 MUg/50
      MUl) each augmented pulmonary fibrosis in wild-type C57BL/6J (WT) mice after 3
      weeks as assessed by histology, fibrosis score, lung collagen via Sircol, and
      type 1 collagen expression; these effects persisted at 2 months. Compared with WT
      mice, Ogg1 homozygous knockout (Ogg1(-/-)) mice exhibit increased pulmonary
      fibrosis after crocidolite exposure and apoptosis in cells at the bronchoalveolar
      duct junctions as assessed via cleaved caspase-3 immunostaining. AEC involvement
      was verified by colocalization studies using surfactant protein C. Asbestos
      increased endoplasmic reticulum stress in the lungs of WT and Ogg1(-/-) mice.
      Compared with WT, alveolar type 2 cells isolated from Ogg1(-/-) mice have
      increased mtDNA damage, reduced mitochondrial aconitase expression, and increased
      P53 and cleaved caspase-9 expression, and these changes were enhanced 3 weeks
      after crocidolite exposure. These findings suggest an important role for AEC
      mtDNA integrity maintained by OGG1 in the pathogenesis of pulmonary fibrosis that
      may represent a novel therapeutic target. 

PMID- 24918272
TI  - Comparison of efficacy and safety between a segmental thermo-expandable metal
      alloy spiral stent (Memokath 051) and a self-expandable covered metallic stent
      (UVENTA) in the management of ureteral obstructions.
AB  - OBJECTIVE: To determine the efficacy and safety of the Memokath 051TM (PNN
      Medical, Glostrup, Denmark) and UVENTATM (Taewoong Medical, Seoul, Korea) metal
      stents, we reviewed our experience with these two metallic ureteral stents for
      treating benign and malignant ureteral obstructions. SUBJECTS AND METHODS: Twenty
      seven patients who received treatment with metallic ureteral stents (Memokath
      051, 10 patients; UVENTA, 17 patients) from November 2011 to May 2013 at our
      institution were identified and analyzed. We conducted a comparative analysis of
      the causes of obstruction, technical/clinical success rate, cause of failure, and
      complications. RESULTS: No difference was observed between the two metallic
      stents for the causes of benign and malignant ureteral obstructions (P=.073). The
      Memokath 051 and the UVENTA were inserted successfully in all ureters using a
      retrograde technique. The mean follow-up was 13.6 months for Memokath 051 and 12
      months for UVENTA (P=.244). The clinical success rate of the UVENTA was higher
      than that of Memokath 051 (82.4% versus 42.9%; P=.031). The causes of failure
      were obstruction by tumor progression (n=2) and stent migration (n=6) in cases
      that received Memokath 051 and stent migration (n=1) and obstruction by mucosal
      hyperplasia (n=2) in UVENTA. The complications caused by Memokath 051 were
      intermittent flank pain (n=1) and acute pyelonephritis (n=1), whereas those of
      UVENTA were intermittent flank pain (n=1), gross hematuria (n=1), and acute
      pyelonephritis (n=1). CONCLUSIONS: The UVENTA achieved a higher clinical success
      rate than the Memokath 051. Our study demonstrated that the UVENTA is safe and
      effective in the management of benign and malignant ureteral obstruction. The
      complications were similar between the two metallic stents.

PMID- 24918273
TI  - [Very late effects of radiotherapy -  limiting factor of current radiotherapy
      techniques].
AB  - BACKGROUND: Very late effects of radiotherapy occur within decades after the
      initial exposure. Their development is induced by low doses of ionizing radiation
      (from 4 Gy per radiation series) and their clinical manifestations are difficult
      to distinguish from other independent diseases diagnosed in individuals not
      formerly treated with radiation. A long time period from the exposure confounds
      any causal relationships between radiation and adverse events. Still, these side
      effects not only reduce the patients quality of life but also lead to an early
      morbidity and mortality, hence generating significant costs in health care and
      social systems. PURPOSE: This article summarizes findings about the most common
      very late consequences of radiotherapy, which include cardiotoxicity, CNS
      toxicity, pneumotoxicity, renal toxicity and secondary malignancies. This issue
      is crucial in the group of children cancer patients, malignant lymphomas,
      testicular tumors and CNS tumors. Generally, the risk of very late effects of
      radiotherapy (RT) should be considered in all patients irradiated at a relatively
      early age with a high chance of long term survival. The risk of very late effects
      of RT is also one of the key limiting factors in the use of RT in the treatment
      of patients with benign lesions with longterm survival expectation, e. g. in
      patients with glomus tumors, neurofibromas, desmoid tumors or hemangiomas or
      other benign lesions (arterio venous malformations). Currently, the only known
      prevention of these very late adverse effects is to minimize the dose to critical
      structures to the lowest achievable level.

PMID- 24918274
TI  - [The combination of neoadjuvant chemoradiotherapy and epidermal growth factor
      receptor inhibitors in the treatment of rectal adenocarcinoma].
AB  - Rectal adenocarcinoma, in contrast to colorectal carcinoma, is typical of its
      high local reccurence rate. Radiotherapy is proved to reduce the incidence of
      recurrences. Neoadjuvant chemoradiotherapy demonstrated better treatment results
      than adjuvant chemoradiotherapy. Standard cytotoxic agents involved in
      combination therapy are 5- flurouracil or capecitabin. Epidermal growth factor
      receptor (EGFR) is supposed to play an important role in cell- cycle regulation,
      proliferation, differentiation, and surviving of normal epithelial tissues. EGFR
      overexpression in patients with rectal adenocarcinoma is associated with
      radioresistance of malignant tissues, lower rates of patological complete
      response after neoadjuvant chemoradiation and generally poor survival. There are
      many clinical studies describing combination of neoadjuvant chemoradiotherapy
      with EGFR inhibitors, however, this regimen has not gained an acceptance as a
      standard of treatmentment.

PMID- 24918275
TI  - [Effect of vitamin d receptor polymorphisms on the development and progression of
      malignant melanoma].
AB  - BACKGROUND: Malignant melanoma is one of the most aggressive cutaneous tumors in
      men and women. The risk of developing a malignant melanoma depends on several
      external factors along with deregulation of mutual interaction of genotype and
      phenotype. Nowadays, growing attention is focused on the study of the
      interactions of the active form of vitamin D3 with its receptor and inhibitory
      effect of vitamin D3 receptor polymorphisms on multiple signaling pathways
      involved in proliferative and metastatic processes. OBJECTIVES: This review
      article addresses the relationship between factors involved in the development of
      malignant melanoma through Hedgehog signaling pathway (HH). It summarizes current
      knowledge of malignant melanoma in regard to the role of the active form of
      vitamin D3 binding to vitamin D3 receptor (VDR), as well as it describes the
      influence of polymorphisms of VDR on the inhibition of HH. Understanding of these
      mechanisms and critical assessment of available data is beneficial to both
      primary and secondary prevention of malignant melanoma particularly by means of
      chemo -preventive substances.

PMID- 24918276
TI  - Analysis of disease-free survival and overall survival in patients with luminal a
      breast cancer stratified according to TNM.
AB  - BACKGROUND AND AIM: The TNM classification of malignant tumours is the most
      commonly used system to assess the stage as well as the prognosis of cancer.
      However, one of the biggest challenges in treatment of breast cancer is the
      understanding of tumour heterogeneity typical of these carcinomas. The aim of
      this study was to analyse the disease-free survival and overall survival in
      patients with luminal A subtype of breast cancer, stratified by TNM staging
      system. METHODS AND STUDY DESIGN: A total of 363 medical records from January
      2001 to May 2006 were evaluated for data collection. There were 136 patients with
      luminal A breast cancer, selected for the cohort. The main objective was the
      analysis of disease-free survival (DFS) and overall survival (OS) in patients
      with luminal A breast cancer, stratified according to the TNM classification.
      RESULTS: The group of 136 patients with immunohistochemically defined luminal A
      subtype represented 53% of the 253 patients with breast cancer. There was no
      significant difference in the number and type of patients as for TNM stage and
      histological grading among patients treated with chemotherapy and HT in
      comparison to patients treated with HT alone. CONCLUSION: Our analysis did not
      prove any significant difference in survival of patients treated with
      chemotherapy followed by hormone therapy in comparison to patients treated with
      HT alone. We suggest that the IHC luminal A subtype of breast cancer generally
      warrants a good prognosis independently on other prognostic factors such as TNM
      stage. We conclude that patients might not benefit of adding a chemotherapy to
      hormonal therapy in adjuvant settings.

PMID- 24918277
TI  - [Molecular cytogenetic analysis of chromosomal aberrations in cells of low grade
      gliomas and its contribution for tumour classification].
AB  - BACKGROUND: Low-grade gliomas represent a heterogeneous group of primary brain
      malignancies. The current diagnostics of these tumors rely strongly on
      histological classification. With the development of molecular cytogenetic
      methods several genetic markers were described, contributing to a better
      distinction of glial subtypes. The aim of this study was to assess the frequency
      of acquired chromosomal aberrations in lowgrade gliomas and to search for new
      genomic changes associated with higher risk of tumor progression. PATIENTS AND
      METHODS: We analysed biopsy specimens from 41 patients with histological dia
      gnosis of low-grade glioma using interphase fluorescence in situ hybridization (I
      FISH) and single nucleotide polymorphism (SNP) array techniques (19 females and
      22 males, medium age 42 years). RESULTS: Besides notorious and most frequent
      finding of combined deletion of 1p/ 19q (81.25% patients) several other recurrent
      aberrations were described in patients with oligodendrogliomas: deletions of p
      and q arms of chromosome 4 (25% patients), deletions of the short arms of
      chromosome 9 (18.75% patients), deletions of the long arms of chromosome 13 and
      monosomy of chromosome 18 (18.75% patients). In bio-psy specimens from patients
      with astrocytomas, we often observed deletion of 1p (24% patients), amplification
      of the long arms of chromosome 7 (16% patients), deletion of the long arm of
      chromosome 13 (20% patients), segmental uniparental disomy (UPD) of the short
      arms of chromosome 17 (60% patients) and deletion of the long arms of chromosome
      19 (28% patients). In one patient we detected a shuttered chromosome 10 resulting
      from chromothripsis. CONCLUSION: Using a combination of I FISH and SNP array, we
      detected not only known chromosomal changes but also new or less frequent recur
      rent aberrations. Their role in cancer  cell progression and their impact on low
      grade gliomas classification remains to be elucidated in a larger cohort of
      patients.

PMID- 24918278
TI  - [Cost analysis of radiotherapy provided in inpatient setting -  testing potential
      predictors for a new prospective payment system].
AB  - BACKGROUND: As a part of the development of a new prospective payment model for
      radiotherapy we analyzed data on costs of care provided by three comprehensive
      cancer centers in the Czech Republic. Our aim was to find a combination of
      variables (predictors) which could be used to sort hospitalization cases into
      groups according to their costs, with each group having the same reimbursement
      rate. We tested four variables as possible predictors -  number of fractions,
      stage of disease, radiotherapy technique and diagnostic group. METHODS: We
      analyzed 7,440 hospitalization cases treated in three comprehensive cancer
      centers from 2007 to 2011. We acquired data from the I COP database developed by
      Institute of Biostatistics and Analyses of Masaryk University in cooperation with
      oncology centers that contains records from the National Oncological Registry
      along with data supplied by healthcare providers to insurance companies for the
      purpose of retrospective reimbursement. RESULTS: When comparing the four
      variables mentioned above we found that number of fractions and radiotherapy
      technique were much stronger predictors than the other two variables. Stage of
      disease did not prove to be a relevant indicator of cost distinction. There were
      significant differences in costs among diagnostic groups but these were mostly
      driven by the technique of radiotherapy and the number of fractions. Within the
      diagnostic groups, the distribution of costs was too heterogeneous for the
      purpose of the new payment model. CONCLUSION: The combination of number of
      fractions and radiotherapy technique appears to be the most appropriate cost
      predictors to be involved in the prospective payment model proposal. Further
      analysis is planned to test the predictive value of intention of radiotherapy in
      order to determine differences in costs between palliative and curative
      treatment.

PMID- 24918279
TI  - [Inverted papiloma and its rare forms].
AB  - Authors address the issue of a frequent benign tumour of the nasal cavity and
      paranasal sinuses -  inverted papilloma. They analyse the available diagnostic
      methods and treatment options. On the background of selected case reports of a
      rare malignant transformation they emphasize the need for longterm
      dispensarization as a part of management plan for patients with this oncological
      disease.

PMID- 24918280
TI  - [Case report of a patient with advanced and disseminated gastric carcinoma
      treated by s-1].
AB  - BACKGROUND: Prognosis of patients with metastatic gastric cancer is abysmal,
      usually just a few months. S-1 is a peroral fluoropyrimidine antitumor drug. It
      is a fixed combination of three effective drugs - tegafur, gimeracil and oteracil
      potassium. CASE: This is a case report of a 71-year-old man treated for local
      advanced and metastatic gastric carcinoma treated with combination of S-1 and
      cisplatin as a first line of therapy. Treatment response reached partial
      remission and lasted for six months. Treatment was very well tolerated, with no
      grade 3 and 4 toxicity. After progression, the patient was treated with further
      lines of therapy. CONCLUSION: In the Czech Republic, experience with S-1 drug is
      very limited. Our case report showed a good treatment response and minimal
      toxicity of this treatment, in concordance with results of the study FLAGS.

PMID- 24918281
TI  - [Cancer in elderly].
AB  - BACKGROUND: Population ageing in developed countries associated with increasing
      cancer incidence in higher age categories becomes a serious challenge in oncology
      nowadays. AIM: To review the present policy of management of senior cancer
      patients and to outline strategies of its improvement. Elderly patients are
      generally undertreated if we address current treatment standards. The elderly
      population is heterogenous in terms of functional status, physical and psychical
      impairment, comorbidities, functional reserve, socioeconomic backgroud and
      geriatric symptoms. There is a lack of consensus on guidelines for elderly
      population due to under-representation of older patients in clinical trials.
      Geriatric assessments could be a useful tool for medical decision making and
      adjusting treatment plan for a certain group of patients - those suitable for
      standard treatment, vulnerable group - advisable to treatment reduction, and
      frail patients - indicated for paliative approach. However, studies confirming
      effectiveness of this age-specific approach in comparison with routine clinical
      practice remain to be conducted. CONCLUSION: Clinical studies focused on senior
      cancer patients are urgently needed.

PMID- 24918282
TI  - Bevacizumab as secondline treatment of glioblastoma -  worth the effort?
AB  - OBJECTIVE: To evaluate the role of bevacizumab and irinotecan as secondline
      treatment of glioblastoma in patients with progression after radiotherapy and
      temozolomide. METHODS: A retrospective analysis of 16 subjects was performed with
      overall survival and toxicity evaluation as the primary endpoint. RESULTS: The
      analysis revealed serious toxicity of this highly expensive regimen without
      proving an improvement in overall survival of patients in comparison to a control
      group. CONCLUSION: Unless there are robust data from phase III clinical trials,
      including quality of life assessments or evaluation of predictive bio-markers to
      guide therapy, bevacizumab and irinotecan regimen should be spared for cautiously
      selected patients, especially in countries with limited budget for oncological
      treatment.

PMID- 24918283
TI  - Design and electronic structure of new styryl dye bases: steady-state and time
      resolved spectroscopic studies.
AB  - A comprehensive investigation of the electronic structure and fast relaxation
      processes in the excited states of new styryl base-type derivatives was performed
      using steady-state, pico-, and femtosecond time-resolved spectroscopic
      techniques. Linear photophysical parameters of new compounds, including steady
      state absorption, fluorescence, and excitation anisotropy spectra, were obtained
      in a number of organic solvents at room temperature. A detailed analysis of the
      fluorescence lifetimes and ultrafast relaxation processes in the electronically
      excited state of the styryl bases revealed an important role of solvate dynamics
      and donor-acceptor strength of the molecular structures in the formation of their
      excited state absorption spectra. Experimental data were in good agreement with
      quantum chemical calculations at the time dependent density functional theory
      level, combined with a polarizable continuum model. 

PMID- 24918284
TI  - Entangled two-dimensional coordination networks: a general survey.

PMID- 24918285
TI  - Screening and functional analysis of the peroxiredoxin specifically expressed in
      Bursaphelenchus xylophilus--the causative agent of pine wilt disease.
AB  - The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine
      wilt disease. Accurately differentiating B. xylophilus from other nematodes
      species, especially its related species B. mucronatus, is important for pine wood
      nematode detection. Thus, we attempted to identify a specific protein in the pine
      wood nematode using proteomics technology. Here, we compared the proteomes of B.
      xylophilus and B. mucronatus using Two-dimensional gel electrophoresis (2-DE) and
      matrix-assisted laser desorption/ionization -time-of-flight/time-of-flight (MALDI
      TOF/TOF-MS) technologies. In total, 15 highly expressed proteins were identified
      in B. xylophilus compared with B. mucronatus. Subsequently, the specificity of
      the proteins identified was confirmed by PCR using the genomic DNA of other
      nematode species. Finally, a gene encoding a specific protein (Bx-Prx) was
      obtained. This gene was cloned and expressed in E. coli. The in situ
      hybridisation pattern of Bx-Prx showed that it was expressed strongly in the tail
      of B. xylophilus. RNAi was used to assess the function of Bx-Prx, the results
      indicated that the gene was associated with the reproduction and pathogenicity of
      B. xylophilus. This discovery provides fundamental information for identifying B.
      xylophilus via a molecular approach. Moreover, the purified recombinant protein
      has potential as a candidate diagnostic antigen of pine wilt disease, which may
      lead to a new immunological detection method for the pine wood nematode. 

PMID- 24918286
TI  - SUMOylation of FOXM1B alters its transcriptional activity on regulation of MiR
      200 family and JNK1 in MCF7 human breast cancer cells.
AB  - Transcription factor Forkhead Box Protein M1 (FOXM1) is a well-known master
      regulator in controlling cell-cycle pathways essential for DNA replication and
      mitosis, as well as cell proliferation. Among the three major isoforms of FOXM1,
      FOXM1B is highly associated with tumor growth and metastasis. The activities of
      FOXM1B are modulated by post-translational modifications (PTMs), such as
      phosphorylation, but whether it is modified by small ubiquitin-related modifier
      (SUMO) remains unknown. The aim of the current study was to determine whether
      FOXM1B is post-translationally modified by SUMO proteins and also to identify
      SUMOylation of FOXM1B on its target gene transcription activity. Here we report
      that FOXM1B is clearly defined as a SUMO target protein at the cellular levels.
      Moreover, a SUMOylation protease, SENP2, significantly decreased SUMOylation of
      FOXM1B. Notably, FOXM1B is selectively SUMOylated at lysine residue 463. While
      SUMOylation of FOXM1B is required for full repression of its target genes MiR
      200b/c and p21, SUMOylation of FOXM1B is essential for full activation of JNK1
      gene. Overall, we provide evidence that FOXM1B is post-translationally modified
      by SUMO and SUMOylation of FOXM1B plays a functional role in regulation of its
      target gene activities. 

PMID- 24918287
TI  - The calcium phosphate matrix of FGF-2-apatite composite layers contributes to
      their biological effects.
AB  - The purpose of the present study was to fabricate fibroblast growth factor (FGF)
      2-apatite composite layers on titanium (Ti) pins in one step at 25  degrees C
      using a supersaturated calcium phosphate (CaP) solution, and to evaluate the
      physicochemical characteristics and biological effects of the coated Ti pins
      compared with coated Ti pins fabricated at 37  degrees C. Ti pins were immersed
      in a supersaturated CaP solution containing 0.5, 1.0, or 2.0 ug/mL FGF-2 at 25 
      degrees C for 24 h (25F0.5, 25F1.0, and 25F2.0) or containing 4.0 ug/mL FGF-2 at
      37  degrees C for 48 h (37F4.0). Except for the 25F0.5, the chemical compositions
      and the mitogenic activity levels of FGF-2 of the composite layers formed by
      these two methods were similar, except for the Ca/P molar ratio, which was
      markedly smaller at 25  degrees C (1.55-1.56+/-0.01-0.02, p=0.0008-0.0045) than
      at 37  degrees C (1.67+/-0.11). Thus, either the apatite was less mature or the
      amount of amorphous calcium phosphate was higher in the composite layer formed at
      25  degrees C. In vivo, the pin tract infection rate by visual inspection for
      37F4.0 (45%) was lower than that for 25F1.0 (80%, p=0.0213), and the rate of
      osteomyelitis for 37F4.0 (35%) was lower than that for 25F0.5 (75%, p=0.0341).
      The extraction torque for 37F4.0 (0.276+/-0.117 Nm) was higher than that for
      25F0.5 (0.192+/-0.117 Nm, p=0.0142) and that for 25F1.0 (0.176+/-0.133 Nm,
      p=0.0079). The invasion rate of S. aureus for 37F4.0 (35%) was lower than that
      for 25F0.5 (75%, p=0.0110). On the whole, the FGF-2-apatite composite layer
      formed at 25  degrees C tended to be less effective at improving fixation
      strength in the bone-pin interface and resisting pin tract infections. These
      results suggest that the chemistry of the calcium phosphate matrix that embeds
      FGF-2, in addition to FGF-2 content and activity, has a significant impact on
      composite infection resistance and fixation strength.

PMID- 24918288
TI  - Mechanisms of enzyme-catalyzed reduction of two carcinogenic nitro-aromatics, 3
      nitrobenzanthrone and aristolochic acid I: Experimental and theoretical
      approaches.
AB  - This review summarizes the results found in studies investigating the enzymatic
      activation of two genotoxic nitro-aromatics, an environmental pollutant and
      carcinogen 3-nitrobenzanthrone (3-NBA) and a natural plant nephrotoxin and
      carcinogen aristolochic acid I (AAI), to reactive species forming covalent DNA
      adducts. Experimental and theoretical approaches determined the reasons why human
      NAD(P)H: quinone oxidoreductase (NQO1) and cytochromes P450 (CYP) 1A1 and 1A2
      have the potential to reductively activate both nitro-aromatics. The results also
      contributed to the elucidation of the molecular mechanisms of these reactions.
      The contribution of conjugation enzymes such as N,O-acetyltransferases (NATs) and
      sulfotransferases (SULTs) to the activation of 3-NBA and AAI was also examined.
      The results indicated differences in the abilities of 3-NBA and AAI metabolites
      to be further activated by these conjugation enzymes. The formation of DNA
      adducts generated by both carcinogens during their reductive activation by the
      NOQ1 and CYP1A1/2 enzymes was investigated with pure enzymes, enzymes present in
      subcellular cytosolic and microsomal fractions, selective inhibitors, and animal
      models (including knock-out and humanized animals). For the theoretical
      approaches, flexible in silico docking methods as well as ab initio calculations
      were employed. The results summarized in this review demonstrate that a
      combination of experimental and theoretical approaches is a useful tool to study
      the enzyme-mediated reaction mechanisms of 3-NBA and AAI reduction.

PMID- 24918290
TI  - Eicosapentaenoic acid protects against palmitic acid-induced endothelial
      dysfunction via activation of the AMPK/eNOS pathway.
AB  - Recent studies have shown that free fatty acids are associated with chronic
      inflammation, which may be involved in vascular injury. The intake of
      eicosapentaenoic acid (EPA) can decrease cardiovascular disease risks, but the
      protective mechanisms of EPA on endothelial cells remain unclear. In this study,
      primary human umbilical vein endothelial cells (HUVECs) treated with palmitic
      acid (PA) were used to explore the protective effects of EPA. The results
      revealed that EPA attenuated PA-induced cell death and activation of apoptosis
      related proteins, such as caspase-3, p53 and Bax. Additionally, EPA reduced the
      PA-induced increase in the generation of reactive oxygen species, the activation
      of NADPH oxidase, and the upregulation of inducible nitric oxide synthase (iNOS).
      EPA also restored the PA-mediated reduction of endothelial nitric oxide synthase
      (eNOS) and AMP-activated protein kinase (AMPK) phosphorylation. Using AMPK siRNA
      and the specific inhibitor compound C, we found that EPA restored the PA-mediated
      inhibitions of eNOS and AKT activities via activation of AMPK. Furthermore, the
      NF-kappaB signals that are mediated by p38 mitogen-activated protein kinase
      (MAPK) were involved in protective effects of EPA. In summary, these results
      provide new insight into the possible molecular mechanisms by which EPA protects
      against atherogenesis via the AMPK/eNOS-related pathway. 

PMID- 24918291
TI  - Functional characterization of NIPBL physiological splice variants and eight
      splicing mutations in patients with Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder
      characterized by distinctive craniofacial features, growth retardation, cognitive
      impairment, limb defects, hirsutism, and multisystem involvement. Mutations in
      five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally
      associated factors (NIPBL, HDAC8) of the cohesin complex have been found in
      patients with CdLS. In about 60% of the patients, mutations in NIPBL could be
      identified. Interestingly, 17% of them are predicted to change normal splicing,
      however, detailed molecular investigations are often missing. Here, we report the
      first systematic study of the physiological splicing of the NIPBL gene, that
      would reveal the identification of four new splicing isoforms DeltaE10, DeltaE12,
      DeltaE33,34, and B'. Furthermore, we have investigated nine mutations affecting
      splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations
      have been examined on the DNA and RNA level, as well as by in silico analyses.
      Although patients with mutations affecting NIPBL splicing show a broad clinical
      variability, the more severe phenotypes seem to be associated with aberrant
      transcripts resulting in a shift of the reading frame. 

PMID- 24918289
TI  - Erythropoietin action in stress response, tissue maintenance and metabolism.
AB  - Erythropoietin (EPO) regulation of red blood cell production and its induction at
      reduced oxygen tension provides for the important erythropoietic response to
      ischemic stress. The cloning and production of recombinant human EPO has led to
      its clinical use in patients with anemia for two and half decades and has
      facilitated studies of EPO action. Reports of animal and cell models of ischemic
      stress in vitro and injury suggest potential EPO benefit beyond red blood cell
      production including vascular endothelial response to increase nitric oxide
      production, which facilitates oxygen delivery to brain, heart and other non
      hematopoietic tissues. This review discusses these and other reports of EPO
      action beyond red blood cell production, including EPO response affecting
      metabolism and obesity in animal models. Observations of EPO activity in cell and
      animal model systems, including mice with tissue specific deletion of EPO
      receptor (EpoR), suggest the potential for EPO response in metabolism and
      disease. 

PMID- 24918292
TI  - Up-regulation of Rhoa/Rho kinase pathway by translationally controlled tumor
      protein in vascular smooth muscle cells.
AB  - Translationally controlled tumor protein (TCTP), a repressor for Na,K-ATPase has
      been implicated in the development of systemic hypertension, as proved by TCTP
      over-expressing transgenic (TCTP-TG) mice. Aorta of TCTP-TG exhibited
      hypercontractile response compared to that of non-transgenic mice (NTG)
      suggesting dys-regulation of signaling pathways involved in the vascular
      contractility by TCTP. Because dys-regulation of RhoA/Rho kinase pathway is
      implicated in increased vascular contractility, we examined whether TCTP induces
      alterations in RhoA pathway in vascular smooth muscle cells (VSMCs). We found
      that TCTP over-expression by adenovirus infection up-regulated RhoA pathway
      including the expression of RhoA, and its downstream signalings, phosphorylation
      of myosin phosphatase target protein (MYPT-1), and myosin light chain (MLC).
      Conversely, lentiviral silencing of TCTP reduced the RhoA expression and Rho
      kinase signalings. Using immunohistochemical and Western blotting studies on
      aortas from TCTP-TG confirmed the elevated expression of RhoA and increase in p
      MLC (phosphorylated MLC). In contrast, down-regulation of RhoA and p-MLC were
      found in aortas from heterozygous mice with deleted allele of TCTP (TCTP+/-). We
      conclude that up-regulation of TCTP induces RhoA-mediated pathway, and that TCTP
      induced RhoA plays a role in the regulation in vasculature. Modulation of TCTP
      may offer a therapeutic target for hypertension and in vascular contractility
      dysfunction. 

PMID- 24918294
TI  - The metallothionein gene, TaMT3, from Tamarix androssowii confers Cd2+ tolerance
      in tobacco.
AB  - Cadmium (Cd) is a nonessential microelement and low concentration Cd2+ has strong
      toxicity to plant growth. Plant metallothioneins, a class of low molecular,
      cystein(Cys)-rich and heavy-metal binding proteins, play an important role in
      both metal chaperoning and scavenging of reactive oxygen species (ROS) with their
      large number of cysteine residues and therefore, protect plants from oxidative
      damage. In this study, a metallothionein gene, TaMT3, isolated from Tamarix
      androssowii was transformed into tobacco (Nicotiana tobacum) through
      Agrobacterium-mediated leaf disc method, and correctly expressed under the
      control of 35S promoter. Under Cd2+ stress, the transgenic tobacco showed
      significant increases of superoxide dismutase (SOD) activity and chlorophyll
      concentration, but decreases of peroxidase (POD) activity and malondialdehyde
      (MDA) accumulation when compared to the non-transgenic tobacco. Vigorous growth
      of transgenic tobacco was observed at the early development stages, resulting in
      plant height and fresh weight were significantly larger than those of the non
      transgenic tobacco under Cd2+ stress. These results demonstrated that the
      expression of the exogenous TaMT3 gene increased the ability of ROS cleaning-up,
      indicating a stronger tolerance to Cd2+ stress. 

PMID- 24918293
TI  - Viral metagenomics on animals as a tool for the detection of zoonoses prior to
      human infection?
AB  - Many human viral infections have a zoonotic, i.e., wild or domestic animal,
      origin. Several zoonotic viruses are transmitted to humans directly via contact
      with an animal or indirectly via exposure to the urine or feces of infected
      animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and
      replicate in its new human host, human-to-human transmissions may occur, possibly
      resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus,
      predicting emerging zoonotic infections is an important challenge for public
      health officials in the coming decades. The recent development of viral
      metagenomics, i.e., the characterization of the complete viral diversity isolated
      from an organism or an environment using high-throughput sequencing technologies,
      is promising for the surveillance of such diseases and can be accomplished by
      analyzing the viromes of selected animals and arthropods that are closely in
      contact with humans. In this review, we summarize our current knowledge of viral
      diversity within such animals (in particular blood-feeding arthropods, wildlife
      and domestic animals) using metagenomics and present its possible future
      application for the surveillance of zoonotic and arboviral diseases. 

PMID- 24918295
TI  - Prediction of protein S-nitrosylation sites based on adapted normal distribution
      bi-profile Bayes and Chou's pseudo amino acid composition.
AB  - Protein S-nitrosylation is a reversible post-translational modification by
      covalent modification on the thiol group of cysteine residues by nitric oxide.
      Growing evidence shows that protein S-nitrosylation plays an important role in
      normal cellular function as well as in various pathophysiologic conditions.
      Because of the inherent chemical instability of the S-NO bond and the low
      abundance of endogenous S-nitrosylated proteins, the unambiguous identification
      of S-nitrosylation sites by commonly used proteomic approaches remains
      challenging. Therefore, computational prediction of S-nitrosylation sites has
      been considered as a powerful auxiliary tool. In this work, we mainly adopted an
      adapted normal distribution bi-profile Bayes (ANBPB) feature extraction model to
      characterize the distinction of position-specific amino acids in 784 S
      nitrosylated and 1568 non-S-nitrosylated peptide sequences. We developed a
      support vector machine prediction model, iSNO-ANBPB, by incorporating ANBPB with
      the Chou's pseudo amino acid composition. In jackknife cross-validation
      experiments, iSNO-ANBPB yielded an accuracy of 65.39% and a Matthew's correlation
      coefficient (MCC) of 0.3014. When tested on an independent dataset, iSNO-ANBPB
      achieved an accuracy of 63.41% and a MCC of 0.2984, which are much higher than
      the values achieved by the existing predictors SNOSite, iSNO-PseAAC, the Li et
      al. algorithm, and iSNO-AAPair. On another training dataset, iSNO-ANBPB also
      outperformed GPS-SNO and iSNO-PseAAC in the 10-fold crossvalidation test. 

PMID- 24918298
TI  - Comparison of acute countermovement jump responses after functional isometric and
      dynamic half squats.
AB  - The purpose of this study was to compare acute countermovement jump (CMJ)
      responses after functional isometric (FI) and dynamic half (DH) squats. Ten
      strength-trained males (relative full back squat 1 repetition maximum [1RM]: 1.9
      +/- 0.2) participated in a randomized crossover design study. On 2 separate days,
      participants performed baseline CMJs followed by either FI or DH squats loaded
      with 150% of full back squat 1RM. Further CMJs were performed between 2 and 11
      minutes after FI or DH squats. Kinematic and kinetic CMJ variables were measured.
      There were no differences observed between conditions when peak CMJ variables
      after FI or DH squats were compared with baseline values (p > 0.05).
      Countermovement jump time effects (p <= 0.05) were observed after squats.
      Increases in peak force (p <= 0.05; FI: 3.9%, range: -0.9 to 9.1%; DH: 4.2%,
      range: 0.0-11.5%) and decreases in peak power (p <= 0.05; FI: -0.4%, range: -5.1
      to 4.0%; DH: -1.1%, range: -6.6 to 2.9%) occurred for combined condition data.
      Positive correlations between lower-body strength and the extent or timing of
      acute CMJ responses were not detected (p > 0.05). Because of the apparent lack of
      additive acute CMJ responses, the use of conventional DH squat protocols should
      be considered rather than FI squats in precompetition and training situations.
      Furthermore, the establishment of individual FI and DH squat protocols also seems
      to be necessary, rather than relying on relative lower-body strength to predict
      the nature of acute CMJ responses.

PMID- 24918297
TI  - Triterpenoid saponins from Stauntonia chinensis ameliorate insulin resistance via
      the AMP-activated protein kinase and IR/IRS-1/PI3K/Akt pathways in insulin
      resistant HepG2 cells.
AB  - Inflammation and oxidative stress play crucial roles in the etiology of type 2
      diabetes mellitus. In this study, we examined the anti-diabetic effects of
      triterpenoid saponins extracted from Stauntonia chinensis on stimulating glucose
      uptake by insulin-resistant human HepG2 cells. The results showed that saponin 6
      significantly increased glucose uptake and glucose catabolism. Saponin 6 also
      enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and activated
      the insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/phosphoinositide 3
      kinase (PI3K)/Akt pathway. Therefore, our results suggest that saponins from S.
      chinensis improve glucose uptake and catabolism in hepatic cells by stimulating
      the AMPK and the IR/IRS-1/PI3K/Akt signaling pathways. The results also imply
      that saponins from S. chinensis can enhance glucose uptake and insulin
      sensitivity, representing a promising treatment for type 2 diabetes mellitus. 

PMID- 24918299
TI  - Efficacy of the functional movement screen: a review.
AB  - The aim of this review was to evaluate and synthesize the scientific literature
      of the functional movement screen (FMS)-driven research for scientists and
      strength and conditioning specialists. An additional purpose was to optimize the
      methodological quality of prospective studies. Relevant research was identified
      through using a manual and electronically database search. Thirty-four articles
      met the inclusion criteria and were read, abstracted, and coded for this review.
      The publications were classified into different stages of Bishops Applied
      Research Model for the Sport Sciences (ARMSS). Thirteen descriptive studies
      explored the main tasks in test development like factor structure, objectivity,
      and reliability. They can be classified to the second stage of Bishops Model
      (ARMSS stage 2). Twelve studies covered ability of FMS to predict sporting
      performance and injury risk (ARMSS stages 3 and 4). Seven studies investigated
      the effectiveness of the FMS in designing programs (ARMSS stages 6 and 8). In
      addition, 2 assessed norming data. On the descriptive level, results suggest that
      the FMS is a reliable screen, if the rater is educated and has solid experience
      (>100 trials). Factor analysis describes the FMS as a unitary construct, which is
      an argument against the FMS total score. Studies clearly illustrate its limited
      ability to predict athletic performance. On the contrary, to predict injury risk
      in team sports, the FMS total score is supported by moderate scientific evidence.
      The majority of the FMS based intervention programs showed an improvement on
      general motor quality. However, a randomized trial does not confirm that results.
      Hence, to implement the findings on field, a critical strength and conditioning
      specialist is crucial.

PMID- 24918296
TI  - Alternative splicing in plant immunity.
AB  - Alternative splicing (AS) occurs widely in plants and can provide the main source
      of transcriptome and proteome diversity in an organism. AS functions in a range
      of physiological processes, including plant disease resistance, but its
      biological roles and functional mechanisms remain poorly understood. Many plant
      disease resistance (R) genes undergo AS, and several R genes require
      alternatively spliced transcripts to produce R proteins that can specifically
      recognize pathogen invasion. In the finely-tuned process of R protein activation,
      the truncated isoforms generated by AS may participate in plant disease
      resistance either by suppressing the negative regulation of initiation of
      immunity, or by directly engaging in effector-triggered signaling. Although
      emerging research has shown the functional significance of AS in plant biotic
      stress responses, many aspects of this topic remain to be understood. Several
      interesting issues surrounding the AS of R genes, especially regarding its
      functional roles and regulation, will require innovative techniques and
      additional research to unravel. 

PMID- 24918300
TI  - Validation of a Video Analysis Software Package for Quantifying Movement Velocity
      in Resistance Exercises.
AB  - Sanudo, B, Rueda, D, del Pozo-Cruz, B, de Hoyo, M, and Carrasco, L. Validation of
      a video analysis software package for quantifying movement velocity in resistance
      exercises. J Strength Cond Res 30(10): 2934-2941, 2016-The aim of this study was
      to establish the validity of a video analysis software package in measuring mean
      propulsive velocity (MPV) and the maximal velocity during bench press. Twenty-one
      healthy males (21 +/- 1 year) with weight training experience were recruited, and
      the MPV and the maximal velocity of the concentric phase (Vmax) were compared
      with a linear position transducer system during a standard bench press exercise.
      Participants performed a 1 repetition maximum test using the supine bench press
      exercise. The testing procedures involved the simultaneous assessment of bench
      press propulsive velocity using 2 kinematic (linear position transducer and semi
      automated tracking software) systems. High Pearson's correlation coefficients for
      MPV and Vmax between both devices (r = 0.473 to 0.993) were observed. The
      intraclass correlation coefficients for barbell velocity data and the kinematic
      data obtained from video analysis were high (>0.79). In addition, the low
      coefficients of variation indicate that measurements had low variability.
      Finally, Bland-Altman plots with the limits of agreement of the MPV and Vmax with
      different loads showed a negative trend, which indicated that the video analysis
      had higher values than the linear transducer. In conclusion, this study has
      demonstrated that the software used for the video analysis was an easy to use and
      cost-effective tool with a very high degree of concurrent validity. This software
      can be used to evaluate changes in velocity of training load in resistance
      training, which may be important for the prescription and monitoring of training
      programmes. 

PMID- 24918301
TI  - Live vs. digital video disk exercise in college--aged females.
AB  - Although exercise digital video disk (DVD) sales have substantially increased
      over the past decade, little is known on the effectiveness of personal training
      vs. DVD exercises. The purpose of this study was to compare energy expenditures
      and heart rates of live and DVD vigorously intense exercise sessions. Twenty
      active and low-to-moderate fit, college-aged females completed 2 identical
      exercise sessions. Each exercise session consisted of 6 exercises; 1 session was
      completed with a personal trainer and the other with a DVD. A portable metabolic
      analyzer was used to measure oxygen consumption and record heart rate. Both
      energy expenditure (p < 0.001) and heart rate (p = 0.001) were significantly
      higher during the live exercise session as compared with the DVD exercise
      session. Rate of perceived exertion was significantly higher for the live
      exercise session compared with the DVD exercise session (p = 0.045). Finally, the
      majority (89%) of the participants reported that they preferred the live exercise
      session over the DVD exercise session. The results suggest that low-to-moderately
      fit college-aged females not only prefer exercise sessions with a personal
      trainer but will also demonstrate higher energy expenditures and heart rates.

PMID- 24918302
TI  - Small-sided games in team sports training: a brief review.
AB  - Small-sided games (SSGs) incorporating skills, sport-specific movements, at
      intensities sufficient to promote aerobic adaptations, are being increasingly
      implemented in professional team sport environments. Small-sided games are often
      employed by coaches based on the premise that the greatest training benefits
      occur when training simulates the specific movement patterns and physiological
      demands of the sport. At present, there is relatively little information
      regarding how SSG can best be used to improve physical capacities and technical
      and tactical skills in team sports. It is possible that with some modifications
      (e.g., number of players, pitch size, coach encouragement, and wrestling), such
      games may be physiologically beneficial for athletes with relatively high initial
      aerobic fitness levels. For instance, it has been shown that 3-a-side soccer SSG
      resulted in higher intensity (i.e., greater overall distance, less jogging and
      walking, higher heart rate, and more tackling, dribbling, goal attempts, and
      passes) than 5-a-side SSG. Likewise, when player numbers were kept constant, a
      larger playing area increased the intensity of the SSG with a smaller playing
      area having the opposite effect. It has also been demonstrated that energy
      expenditure was similar between badminton and volleyball courts, but lower than
      that obtained in a basketball court. Moreover, it has been demonstrated in rugby
      that wrestling can increase the physical demands of SSG. Consistent coach
      encouragement can also increase training intensity, although most rule changes
      have trivial or no effect on exercise intensity. Further research is required to
      examine the optimal periodization strategies of SSG training for the long-term
      development of physiological capacity, technical skill, and tactical proficiency,
      while also minimizing the associated risk of injuries.

PMID- 24918303
TI  - Perfluoroalkyl acid distribution in various plant compartments of edible crops
      grown in biosolids-amended soils.
AB  - Crop uptake of perfluoroalkyl acids (PFAAs) from biosolids-amended soil has been
      identified as a potential pathway for PFAA entry into the terrestrial food chain.
      This study compared the uptake of PFAAs in greenhouse-grown radish (Raphanus
      sativus), celery (Apium graveolens var. dulce), tomato (Lycopersicon
      lycopersicum), and sugar snap pea (Pisum sativum var. macrocarpon) from an
      industrially impacted biosolids-amended soil, a municipal biosolids-amended soil,
      and a control soil. Individual concentrations of PFAAs, on a dry weight basis, in
      mature, edible portions of crops grown in soil amended with PFAA industrially
      impacted biosolids were highest for perfluorooctanoate (PFOA; 67 ng/g) in radish
      root, perfluorobutanoate (PFBA; 232 ng/g) in celery shoot, and PFBA (150 ng/g) in
      pea fruit. Comparatively, PFAA concentrations in edible compartments of crops
      grown in the municipal biosolids-amended soil and in the control soil were less
      than 25 ng/g. Bioaccumulation factors (BAFs) were calculated for the root, shoot,
      and fruit compartments (as applicable) of all crops grown in the industrially
      impacted soil. BAFs were highest for PFBA in the shoots of all crops, as well as
      in the fruit compartment of pea. Root-soil concentration factors (RCFs) for
      tomato and pea were independent of PFAA chain length, while radish and celery
      RCFs showed a slight decrease with increasing chain length. Shoot-soil
      concentration factors (SCFs) for all crops showed a decrease with increasing
      chain length (0.11 to 0.36 log decrease per CF2 group). The biggest decrease
      (0.54-0.58 log decrease per CF2 group) was seen in fruit-soil concentration
      factors (FCFs). Crop anatomy and PFAA properties were utilized to explain data
      trends. In general, fruit crops were found to accumulate fewer long-chain PFAAs
      than shoot or root crops presumably due to an increasing number of biological
      barriers as the contaminant is transported throughout the plant (roots to shoots
      to fruits). These data were incorporated into a preliminary conceptual framework
      for PFAA accumulation in edible crops. In addition, these data suggest that
      edible crops grown in soils conventionally amended for nutrients with biosolids
      (that are not impacted by PFAA industries) are unlikely a significant source of
      long-chain PFAA exposure to humans. 

PMID- 24918304
TI  - Gait in amyotrophic lateral sclerosis: Is gait pattern differently affected in
      spinal and bulbar onset of the disease during dual task walking?
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by weakness, fatigue, loss
      of balance and coordination. The purpose of the study was to examine gait in ALS
      patients. Gait was compared in ALS with spinal and bulbar onset, while performing
      dual mental and motor tasks. Dual-task walking was performed by 27 ALS patients,
      13 with spinal- and 14 with bulbar-onset disease. Twenty-nine healthy subjects
      were used as a control group. The subjects performed a basic, simple walking
      task, dual-motor task, dual-mental task, and combined motor and mental tasks.
      Results showed that dual-task paradigm has an effect on gait in ALS patients.
      Gait was differently affected in spinal and bulbar onset of ALS by some of the
      given tasks. Mental tasks had a larger effect than motor tasks in all gait
      parameters. In conclusion, both ALS forms have impaired gait in dual tasks.
      Simple walk in patients with spinal onset shows higher variability of certain
      gait parameters compared to bulbar-onset patients and controls. Differences in
      gait could also indicate postural instability and possible falls in complex
      walking situations.

PMID- 24918305
TI  - Chemical protein polyubiquitination reveals the role of a noncanonical
      polyubiquitin chain in DNA damage tolerance.
AB  - Polyubiquitination of proteins regulates a variety of cellular processes,
      including protein degradation, NF-kappaB pathway activation, apoptosis, and DNA
      damage tolerance. Methods for generating polyubiquitinated protein with defined
      ubiquitin chain linkage and length are needed for an in-depth molecular
      understanding of protein polyubiquitination. However, enzymatic protein
      polyubiquitination usually generates polyubiquitinated proteins with mixed chain
      lengths in a low yield. We report herein a new chemical approach for protein
      polyubiquitination with a defined ubiquitin chain length and linkage under a mild
      condition that preserves the native fold of the target protein. In DNA damage
      tolerance, K63-polyubiquitinated proliferating cell nuclear antigen (PCNA) plays
      an important yet unclear role in regulating the selection of the error-free over
      error-prone lesion bypass pathways. Using the chemically polyubiquitinated PCNA,
      we revealed a mechanism of the K63 polyubiquitin chain on PCNA in promoting the
      error-free lesion bypass by suppressing the DNA translesion synthesis (TLS). 

PMID- 24918306
TI  - Nonlinear Calibration Model Choice between the Four and Five-Parameter Logistic
      Models.
AB  - Both the four-parameter logistic (4PL) and the five-parameter logistic (5PL)
      models are widely used in nonlinear calibration. In this paper, we study the
      choice between 5PL and 4PL both by the accuracy and precision of the estimated
      concentrations and by the power to detect an association between a binary disease
      outcome and the estimated concentrations. Our results show that when the true
      curve is symmetric around its inflection point, the efficiency loss from using
      5PL is negligible under the prevalent experimental design. When the true curve is
      asymmetric, 4PL may sometimes offer better performance due to bias-variance trade
      off. We provide a practical guideline for choosing between 5PL and 4PL and
      illustrate its application with a real dataset from the HIV Vaccine Trials
      Network laboratory. 

PMID- 24918307
TI  - An internal focus of attention is not always as bad as its reputation: how
      specific aspects of internally focused attention do not hinder running
      efficiency.
AB  - The aim of this study was to examine differentiated effects of internally focused
      attention in endurance sports. Thirty-two active runners ran 24 min on a
      treadmill at a fixed speed of moderate intensity. For each 6-min block,
      participants had to direct their attention on different internal aspects
      (movement execution, breathing, or feeling of the body) or received no
      instructions. Oxygen consumption (VO2) was measured continuously to determine
      running economy. Results revealed that the different internal focus instructions
      had differentiated effects on VO2: A focus on breathing as well as a focus on the
      running movement led to higher VO2 than a focus on feeling of the body which
      showed similar VO2 as the control condition. We conclude that an internal focus
      of attention is solely detrimental to performance when directed to highly
      automated processes (e.g., breathing or movement). However, an internal focus on
      how the body feels during exercise does not disrupt movement efficiency. 

PMID- 24918308
TI  - Initial development of the Coach Identity Prominence Scale: a role identity model
      perspective.
AB  - The focus of this multiphase research was to generate and test the psychometric
      parameters of the Coach Identity Prominence Scale (CIPS). First, a pilot study
      was conducted with context (n = 10) and construct (n = 6) specialists, who
      evaluated the technical quality and content validity of 20 items developed from
      semistructured interviews. Thirteen items were selected for Study 1, which tested
      the factorial validity and reliability scores of coaches' (n = 343) responses to
      the CIPS items. An eight-item structure, consisting of two factors (centrality
      and evaluative emotions) was selected as the final CIPS measure, which was
      examined with a final sample of coaches (n = 454) in Study 2 to evaluate the
      factorial validity, group invariance, concurrent validity, and nomological
      validity of respondents' scores to the CIPS. Initial evidence for the various
      types of validity and reliability tested across the studies was provided. 

PMID- 24918309
TI  - Fitness level moderates executive control disruption during exercise regardless
      of age.
AB  - The purpose of this study was to assess the effects of exercise intensity, age,
      and fitness levels on executive and nonexecutive cognitive tasks during exercise.
      Participants completed a computerized modified-Stroop task (including
      denomination, inhibition, and switching conditions) while pedaling on a cycle
      ergometer at 40%, 60%, and 80% of peak power output (PPO). We showed that a bout
      of moderate-intensity (60% PPO) to high-intensity (80% PPO) exercise was
      associated with deleterious performance in the executive component of the
      computerized modified-Stroop task (i.e., switching condition), especially in
      lower-fit individuals (p < .01). Age did not have an effect on the relationship
      between acute cardiovascular exercise and cognition. Acute exercise can
      momentarily impair executive control equivalently in younger and older adults,
      but individual's fitness level moderates this relation. 

PMID- 24918310
TI  - Examining the link between framed physical activity ads and behavior among women.
AB  - Gain-framed messages are more effective at promoting physical activity than loss
      framed messages. However, the mechanism through which this effect occurs is
      unclear. The current experiment examined the effects of message framing on
      variables described in the communication behavior change model (McGuire, 1989),
      as well as the mediating effects of these variables on the message-frame-behavior
      relationship. Sixty low-to-moderately active women viewed 20 gain- or loss-framed
      ads and five control ads while their eye movements were recorded via eye
      tracking. The gain-framed ads attracted greater attention, ps < .05; produced
      more positive attitudes, p = .06; were better recalled, p < .001; influenced
      decisions to be active, p = .07; and had an immediate and delayed impact on
      behavior, ps < .05, compared with the loss-framed messages. Mediation analyses
      failed to reveal any significant effects. This study demonstrates the effects of
      framed messages on several outcomes; however, the mechanisms underlying these
      effects remain unclear. 

PMID- 24918311
TI  - Mental toughness in sport: motivational antecedents and associations with
      performance and psychological health.
AB  - We argue that basic psychological needs theory (BPNT) offers impetus to the value
      of mental toughness as a mechanism for optimizing human functioning. We
      hypothesized that psychological needs satisfaction (thwarting) would be
      associated with higher (lower) levels of mental toughness, positive affect, and
      performance and lower (higher) levels of negative affect. We also expected that
      mental toughness would be associated with higher levels of positive affect and
      performance and lower levels of negative affect. Further, we predicted that
      coaching environments would be related to mental toughness indirectly through
      psychological needs and that psychological needs would indirectly relate with
      performance and affect through mental toughness. Adolescent cross-country runners
      (136 male and 85 female, M(age) = 14.36) completed questionnaires pertaining to
      BPNT variables, mental toughness, and affect. Race times were also collected. Our
      findings supported our hypotheses. We concluded that BPNT is generative in
      understanding some of the antecedents and consequences of mental toughness and is
      a novel framework useful for understanding mental toughness.

PMID- 24918312
TI  - Implicit motives and basic need satisfaction in extreme endurance sports.
AB  - Previous research has shown that the effects of basic psychological needs on the
      flow experience in sports are moderated by implicit motives. However, so far,
      only leisure and health-oriented sports have been analyzed. In a pilot study and
      a main study (N = 29, 93), we tested whether the implicit achievement and
      affiliation motives interact with the need for competence and the need for social
      relatedness satisfaction, respectively, to predict flow experience and well-being
      in extreme endurance athletes. Results showed that highly achievement-motivated
      individuals benefited more from the need for competence satisfaction in terms of
      flow than individuals with a low achievement motive did. In addition, highly
      affiliation-motivated individuals whose need for social relatedness is satisfied
      reported higher positive affect and lower exercise addiction scores than athletes
      with a low motive. We discuss the differential effects of the interplay between
      the achievement and affiliation motives and basic needs on different outcome
      variables. 

PMID- 24918313
TI  - Team perfectionism and team performance: a prospective study.
AB  - Perfectionism is a personality characteristic that has been found to predict
      sports performance in athletes. To date, however, research has exclusively
      examined this relationship at an individual level (i.e., athletes' perfectionism
      predicting their personal performance). The current study extends this research
      to team sports by examining whether, when manifested at the team level,
      perfectionism predicts team performance. A sample of 231 competitive rowers from
      36 boats completed measures of self-oriented, team-oriented, and team-prescribed
      perfectionism before competing against one another in a 4-day rowing competition.
      Strong within-boat similarities in the levels of team members' team-oriented
      perfectionism supported the existence of collective team-oriented perfectionism
      at the boat level. Two-level latent growth curve modeling of day-by-day boat
      performance showed that team-oriented perfectionism positively predicted the
      position of the boat in midcompetition and the linear improvement in position.
      The findings suggest that imposing perfectionistic standards on team members may
      drive teams to greater levels of performance. 

PMID- 24918314
TI  - "I'm pretty sure that we will win!": The influence of score-related nonverbal
      behavioral changes on the confidence in winning a basketball game.
AB  - The goal of the present research was to test whether score-related changes in
      opponents' nonverbal behavior influence athletes' confidence in beating their
      opponents. In an experiment, 40 participants who were experienced basketball
      players watched brief video clips depicting athletes' nonverbal behavior. Video
      clips were not artificially created, but showed naturally occurring behavior.
      Participants indicated how confident they were in beating the presented athletes
      in a hypothetical scenario. Results indicated that participants' confidence
      estimations were influenced by opponents' score-related nonverbal behavior.
      Participants were less confident about beating a leading team and more confident
      about beating a trailing team, although they were unaware of the actual score
      during the depicted scenes. The present research is the first to show that in
      game variations of naturally occurring nonverbal behavior can influence athletes'
      confidence. This finding highlights the importance of research into nonverbal
      behavior in sports, particularly in relation to athletes' confidence. 

PMID- 24918316
TI  - Bacteriorhodopsin: Would the real structural intermediates please stand up?
AB  - BACKGROUND: Bacteriorhodopsin (bR) is the simplest known light driven proton pump
      and has been heavily studied using structural methods: eighty four X-ray
      diffraction, six electron diffraction and three NMR structures of bR are
      deposited within the protein data bank. Twenty one X-ray structures report light
      induced structural changes and changes induced by mutation, changes in pH,
      thermal annealing or X-ray induced photo-reduction have also been examined. SCOPE
      OF REVIEW: We argue that light-induced structural changes that are replicated
      across several studies by independent research groups are those most likely to
      represent what is happening in reality. We present both internal distance matrix
      analyses that sort deposited bR structures into hierarchal trees, and difference
      Fourier analysis of deposited X-ray diffraction data. MAJOR CONCLUSIONS: An
      internal distance matrix analysis separates most wild-type bR structures
      according to their different crystal forms, indicating how the protein's
      structure is influenced by crystallization conditions. A similar analysis
      clusters eleven studies of illuminated bR crystals as one branch of a hierarchal
      tree with reproducible movements of the extracellular portion of helix C towards
      helix G, and of the cytoplasmic portion of helix F away from helices A, B and G.
      All crystallographic data deposited for illuminated crystals show negative
      difference density on a water molecule (Wat402) that forms H-bonds to the retinal
      Schiff Base and two aspartate residues (Asp85, Asp212) in the bR resting state.
      Other recurring difference density features indicated reproducible side-chain,
      backbone and water molecule displacements. X-ray induced radiation damage also
      disorders Wat402 but acts via cleaving the head-groups of Asp85 and Asp212.
      GENERAL SIGNIFICANCE: A remarkable level of agreement exists when deposited
      structures and crystallographic observations are viewed as a whole. From this
      agreement a unified picture of the structural mechanism of light-induced proton
      pumping by bR emerges. This article is part of a Special Issue entitled
      Structural biochemistry and biophysics of membrane proteins.

PMID- 24918317
TI  - Crystal melting by light: X-ray crystal structure analysis of an azo crystal
      showing photoinduced crystal-melt transition.
AB  - Trans-cis photoisomerization in an azo compound containing azobenzene
      chromophores and long alkyl chains leads to a photoinduced crystal-melt
      transition (PCMT). X-ray structure analysis of this crystal clarifies the
      characteristic coexistence of the structurally ordered chromophores through their
      pi...pi interactions and disordered alkyl chains around room temperature. These
      structural features reveal that the PCMT starts near the surface of the crystal
      and propagates into the depth, sacrificing the pi...pi interactions. A temporal
      change of the powder X-ray diffraction pattern under light irradiation and a two
      component phase diagram allow qualitative analysis of the PCMT and the following
      reconstructive crystallization of the cis isomer as a function of product
      accumulation. This is the first structural characterization of a compound showing
      the PCMT, overcoming the low periodicity that makes X-ray crystal structure
      analysis difficult. 

PMID- 24918318
TI  - Skin reactions during anti-TNFalpha therapy for pediatric inflammatory bowel
      disease: a 2-year prospective study.
AB  - BACKGROUND: Although the development of therapy-related skin reactions is common
      along with an increase in the number of adult patients receiving anti-TNFalpha,
      there are few studies on pediatric inflammatory bowel disease; hence, this
      prospective study focuses on skin reactions related to infliximab therapy.
      METHODS: All pediatric patients with inflammatory bowel disease undergoing
      infliximab therapy were prospectively screened for the presence of skin
      manifestations at the time of each infusion between March 1, 2011 and March 31,
      2011 at Children's Hospital, Helsinki, Finland. Blood inflammatory markers and
      fecal calprotectin levels were measured at the time of infusions. RESULTS: During
      the study period, 84 children with inflammatory bowel disease (Crohn's n = 64)
      received infliximab infusions (the median duration of therapy 12.2 mo). Almost
      every other patient (n = 40; 47.6%) presented chronic skin reactions, 23% with
      lesions considered severe. Most commonly, the patient's ear lobes and scalp were
      affected with psoriasis-like manifestations, followed by their eyelids, perioral
      and pubic area, trunk, and the extremities. However, an HLA-Cw*0602 genotype
      associating with psoriasis was rare. Interestingly, most patients with skin
      reactions had a low degree of intestinal inflammation based on their fecal
      calprotectin levels (median level, 133 MUg/g versus 589 in unaffected patients; P
      < 0.016). Seven patients (8.3% of all patients but 17% of those with skin
      lesions) discontinued the given therapy due to a skin reaction. CONCLUSIONS: Skin
      reactions are common during maintenance therapy with infliximab in pediatric
      patients. For most patients, skin reactions seem to correlate with a low level of
      intestinal inflammation. Although potentially harsh, skin lesions mostly allow
      continuation of infliximab.

PMID- 24918319
TI  - Fecal biomarkers in the diagnosis and monitoring of Crohn's disease.
AB  - The diagnosis and monitoring of Crohn's disease has traditionally relied on
      clinical assessment, serum markers of inflammation, and endoscopic examination.
      Fecal biomarkers such as calprotectin, lactoferrin, and S100A12 are predominantly
      derived from neutrophils, are easily detectable in the feces, and are emerging as
      valuable markers of intestinal inflammation. This review focuses on the role of
      fecal biomarkers in the diagnosis and monitoring of Crohn's disease, in
      particular how these biomarkers change with disease activity and remission, how
      they can be used to monitor the response to medical therapy, their value in
      predicting clinical relapse, and their role in monitoring the postoperative
      state.

PMID- 24918320
TI  - Treatment patterns, complications, and disease relapse in a real-world population
      of patients with moderate-to-severe ulcerative colitis initiating immunomodulator
      therapy.
AB  - BACKGROUND: Immunomodulator (IM) treatments in ulcerative colitis (UC) are not
      curative and carry increased risk of complications, sometimes leading to therapy
      changes, reduced treatment benefits, and eventual relapse. We assessed patterns
      of IM utilization and therapy changes, complications, and disease relapse in a
      real-world population of patients with moderate-to-severe UC. METHODS: Claims
      data from a large commercially insured U.S. population were retrospectively
      analyzed. Inclusion criteria were (1) >=2 UC diagnosis claims (ICD-9-CM 556.xx)
      between January 2005 and July 2010, (2) >=1 IM claim, where first IM claim
      defined the index date, (3) >=12 months preindex health plan enrollment
      (baseline), and (4) >=24 months postindex plan enrollment (follow-up).
      Characteristics of and changes to the index IM therapy during follow-up were
      descriptively assessed, as were complications and disease relapses. RESULTS: A
      total of 2136 patients were identified for inclusion (age, mean [SD], 46 [16]
      years, 54% female). Azathioprine was the most common index IM (46% of patients),
      followed by 6-mercaptopurine (28%). Switching from the index IM to another
      therapy class was common (21% of patients), with 5-ASAs (48% of switchers), oral
      corticosteroids (21%), and biologics (17%) being the most frequent next agents
      used. Augmentation was also common (25% of patients), with 5-ASA being, by far,
      the most frequent agent added to the index IM (72% of augmenters). Thirty percent
      of patients experienced a complication, and 73% of patients relapsed, with the
      majority of relapses occurring during index IM exposure. CONCLUSIONS: This
      assessment of IM treatments for UC demonstrated frequent changes to therapy and
      high downstream complication and relapse rates.

PMID- 24918321
TI  - Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active
      ulcerative colitis: a meta-analysis.
AB  - BACKGROUND: VSL#3 is a probiotic mix preparation reported to be effective in the
      treatment of mild to moderately active ulcerative colitis. We aimed to perform a
      systematic review of the literature and a meta-analysis of studies on its
      efficacy. METHODS: The searched databases included PubMed, Scopus, and
      ScienceDirect. The Mantel-Haenszel method was used to pool the effect- ize across
      studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of
      experiencing a specific outcome were calculated. RESULTS: Five studies with 441
      patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7
      56.1). Only 3 low risk of bias studies with 319 patients met the inclusion
      criteria for further analysis. A total of 162 patients received 3.6 * 10 CFU/d
      VSL#3, and 157 patients received placebo. A total of 95% of patients received
      concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis
      Disease Activity Index was used to define response and remission. A >50% decrease
      in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the
      VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR,
      2.793; 95% CI, 1.375-5.676; number needed to treat = 4-5). The response rate was
      53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001;
      OR, 3.03; 95% CI, 1.89-4.83; number needed to treat = 3-4). The remission rate
      was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P =
      0007; OR, 2.4; 95% CI, 1.48-3.88; number needed to treat = 4-5). No serious side
      effects were reported. CONCLUSIONS: VSL#3, when added to conventional therapy at
      a daily dose of 3.6 * 10 CFU/d, is safe and more effective than conventional
      therapy alone in achieving higher response and remission rates in mild to
      moderately active ulcerative colitis.

PMID- 24918322
TI  - Impact of mode of delivery on outcomes in patients with perianal Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) often affects women during the reproductive
      years. Although several studies have examined the impact of pregnancy on luminal
      disease, limited literature exists in those with perianal CD. Decision regarding
      mode of delivery is a unique challenge in such patients due to concerns regarding
      the effect of pelvic floor trauma during delivery on preexisting perianal
      involvement. METHODS: We performed a retrospective chart review of patients with
      CD with established perianal disease undergoing either vaginal delivery or
      caesarean section (C-section) at our institutions. We examined the occurrence of
      symptomatic perianal disease flares within 5 years after delivery in such women
      compared with nonpregnant CD controls. We also compared the occurrence of such
      flares between the 2 modes of delivery in women with established perianal CD.
      RESULTS: We identified 61 pregnant patients with CD with established perianal
      disease (11 vaginal delivery, 50 through C-section) and 61 nonpregnant CD
      controls with perianal disease. One-third of the C-sections were primarily for
      obstetric indications. Six of the vaginal deliveries were complicated.
      Approximately, 36% of cases had a symptomatic perianal flare within 1 year after
      delivery. This was similar across both modes of delivery (P = 0.53) and similar
      to nonpregnant patients with CD. There was no difference in the rates of perianal
      surgical intervention or luminal disease flares in our population based on mode
      of delivery or between pregnant patients with CD and nonpregnant CD controls.
      CONCLUSIONS: We observed no difference in risk of symptomatic perianal flares in
      patients with established perianal CD delivering vaginally or through C-section.

PMID- 24918324
TI  - Cuff and pouch cancer in patients with inflammatory bowel disease: what
      surveillance strategy should be recommended?

PMID- 24918323
TI  - Crohn's disease-associated Escherichia coli survive in macrophages by suppressing
      NFkappaB signaling.
AB  - BACKGROUND: Epidemiological and genetic studies suggest a role for enteric flora
      in the pathogenesis of Crohn's disease (CD). Crohn's disease-associated
      Escherichia coli (CDEC) is characterized by their ability to invade epithelial
      cells and survive and induce high concentration of TNF-alpha from infected
      macrophages. However, the molecular mechanisms of CDEC survival in infected
      macrophages are not completely understood. METHODS: Intracellular survival of
      CDEC strain LF82 isolated from inflamed ileum tissue, 13I isolated from inflamed
      colonic tissue, and control E. coli strains were tested in the murine macrophage
      cell line, J774A.1 by Gentamicin protection assay. Modulation of intracellular
      cell signaling pathways by the E. coli strains were assessed by western blot
      analysis and confocal microscopy. RESULTS: 13I demonstrated increased survival in
      macrophages with 2.6-fold higher intracellular bacteria compared with LF82, yet
      both strains induced comparable levels of TNF-alpha. LF82 and 13I differentially
      modulated key mitogen-activated protein kinase pathways during the acute phase of
      infection; LF82 activated all 3 mitogen-activated protein kinase pathways,
      whereas 13I activated ERK1/2 pathway but not p38 and JNK pathways. Both 13I and
      LF82 suppressed nuclear translocation of NFkappaB compared with noninvasive E.
      coli strains during the acute phase of infection. However, unlike noninvasive E.
      coli strains, 13I and LF82 infection resulted in chronic activation of NFkappaB
      during the later phase of infection. CONCLUSIONS: Our results showed that CDEC
      survive in macrophages by initially suppressing NFkappaB activation. However,
      persistence of bacterial within macrophages induces chronic activation of
      NFkappaB, which correlates with increased TNF-alpha secretion from infected
      macrophages.

PMID- 24918325
TI  - Reply to Derikx and Hoentjen.

PMID- 24918326
TI  - On robustness of noninferiority clinical trial designs against bias, variability,
      and nonconstancy.
AB  - The regulatory guidelines on noninferiority (NI) trials emphasize constancy not
      only in the treatment effect over time but also in the trial design, clinical
      practice, and quality of the trial conduct and execution. In practice, the
      constancy assumption is generally impossible to justify; often, there are clear
      reasons to expect a loss of efficacy over time. There are also concerns about the
      inherent and publication bias in the historical data, and various sources of
      selection bias in the NI trial design. Thus, a conservative NI margin is often
      considered. However, different NI margin approaches are largely evaluated under
      the assumption of constancy and absence of bias, and therefore, controversies
      arise and are unresolved on the necessary degree of conservativeness. We develop
      a framework to quantify the robustness of any NI margin approach against inherent
      and publication bias in historical data, selection bias in trial design, and
      nonconstancy in reference effects. We introduce a consistency principle to
      address variability in the historical data. We control across-trial conditional
      error rates given a final NI trial design over a design specific robust range for
      reference effects. Following a conditionality principle, we provide a theoretical
      justification of the framework and the conditions for controlling across-trial
      unconditional type 1 error rates. We raise the issue of inherent bias in
      historical data with an illustrative example. 

PMID- 24918327
TI  - Assessment of cardiotoxicity and effects of malathion on the early development of
      zebrafish (Danio rerio) using computer vision for heart rate quantification.
AB  - Malathion, a common organophosphate insecticide, is a proven acetylcholinesterase
      inhibitor and is the most applied organophosphate insecticide in the United
      States. The use of zebrafish as a model to study the effects of pesticides on
      development is an innovative approach yielding relevant implications for
      determining the potential toxic effects of these pesticides on humans. In this
      study, a simple noninvasive technique was developed to investigate the
      cardiotoxicity of malathion on Danio rerio embryos, and to detect and quantify
      its effect on heart rate. Videos were recorded under a stereomicroscope and
      examined with our custom-made software (FishBeat) to determine the heart rate of
      the embryos. The pixel average intensity frequency (PI) of the videos was
      computed at its maximum probability to indicate the average number of heartbeats
      per second. Experimental observations successfully demonstrated that this method
      was able to detect the heart rate of zebrafish embryos as compared with manual
      stopwatch counting, with no significant difference. Embryos were treated acutely
      with increasing malathion concentrations (33.3 and 50 MUg/mL malathion) at 52,
      76, and 96 hpf. Embryos treated with 33.3 MUg/mL malathion had significant
      bradycardia at 52 and 76 hpf, whereas embryos treated with 50 MUg/mL malathion
      presented bradycardia at all hpf. These novel observations confirmed that
      malathion, acting as an acetylcholinesterase inhibitor, induced heartbeat
      irregularity in zebrafish embryos.

PMID- 24918328
TI  - TA-cloning vectors for rapid and cheap cloning of zebrafish transgenesis
      constructs.

PMID- 24918329
TI  - Combining Classical MD and QM calculations to elucidate complex system
      nucleation: a twisted, three-stranded, parallel beta-sheet seeds amyloid fibril
      conception.
AB  - The crystal structure of the Sup35 prion segment, GNNQQNY, revealed precise side
      chain packing and an extensive H-bond network. However, the conformers and
      stabilizing interactions involved at nascent amyloid formation are still unclear.
      Here, long molecular dynamics simulations and quantum mechanical calculations
      have been utilized to study the conformation and energetics of the initial
      structure that acts to nucleate further growth. Considering all the plausible
      intermediates that may act as stepping stones, we find that the initial nucleus
      is a twisted single-layer, three-stranded parallel beta-sheet. H-bonds between
      beta-strands in this twisted sheet, some of which differ from those of the
      crystal structure's nontwisted beta-strands, are key for the nucleus' formation
      and stability. High level theoretical calculations of these H-bonds' energetics
      can account for this amyloid-like trimer's remarkable stability. The intermeshing
      of facing sheets to form the dry interface provides less stability and would
      occur between two three-stranded beta-sheets without metastable water nanowires. 

PMID- 24918330
TI  - Subparaneural versus circumferential extraneural injection at the bifurcation
      level in ultrasound-guided popliteal sciatic nerve blocks: a prospective,
      randomized, double-blind study.
AB  - BACKGROUND: The ideal spread of local anesthetic for effective, rapid, and safe
      sciatic nerve block is debated. We hypothesized that subparaneural ultrasound
      guided injection results in faster onset and has a better success rate than
      extraneural circumferential spread. METHODS: Patients undergoing elective tibial,
      foot, and ankle surgery with popliteal sciatic nerve blocks were prospectively
      enrolled. After randomization, the needle tip position was adjusted to ensure
      circumferential extraneural or subparaneural spread; 0.3 mL/kg of mepivacaine 10
      mg/mL was injected. Post hoc video analysis was used to group the patients
      according to extraneural, subparaneural, and unintentional intraepineural spread.
      RESULTS: There were 26 (43.3%) patients in the subparaneural group and 22 (36.7%)
      in the extraneural group. Block onset time was shorter in the subparaneural group
      than in the extraneural group (11 [3-21] minutes; mean [95% confidence interval],
      11 [8.97-13.02] minutes and 17 [6-30] minutes; mean [95% confidence interval]
      18.37 [14.17-22.57] minutes, respectively; P = 0.002). The duration of sensory
      blockade increased (397 [178-505] minutes vs 265 [113-525] minutes; P = 0.04).
      The success rate of the block also increased. Unintentional intraepineural
      injection occurred in 8% of patients (3 patients in the subparaneural group and 1
      patient in the extraneural group; NS). Block onset time was shorter than for the
      subparaneural and extraneural groups (6 [3-12] minutes, 12 [3-21] minutes, and 18
      [6-30] minutes; P = 0.01). CONCLUSIONS: A subparaneural injection accelerated the
      onset time and increased the duration of tibial nerve sensory blockade compared
      with circumferential extraneural injection. With unintentional intraepineural
      spread, the onset time was significantly shorter than for the other groups.

PMID- 24918331
TI  - Can changes in vital signs be used to predict the response to lumbar facet blocks
      and radiofrequency denervation? A prospective, correlational study.
AB  - BACKGROUND: Facet joint radiofrequency (RF) ablation is characterized by a high
      failure rate, which is partly due to the fact that pain relief after diagnostic
      blocks is inherently subjective. An area that has yet to be explored is whether
      more objective measures, such as changes in vital signs after blocks, might be
      used to predict treatment outcomes. METHODS: A multicenter, prospective study was
      performed in 223 patients who underwent diagnostic lumbar medial branch blocks,
      of whom 87 proceeded to RF denervation. Blood pressure (BP), heart rate (HR), and
      pain scores were recorded preblock and 20 minutes postblock. A positive vital
      sign response was designated as a decrease of less than 7.5 units in BP or HR,
      and a positive facet block as pain relief of 50% or greater based on 6-hour pain
      diary scores. RESULTS: Overall, 125 subjects (56.1%; 95% confidence interval,
      49.3%-62.6%) experienced a positive facet block, and 71 had 3-month follow-up
      information after denervation. Correlations between changes in NRS scores and HR
      (r = -0.01, P = 0.893), systolic BP (r = 0.05, P = 0.47), diastolic BP (DBP) (r =
      0.08, P = 0.22), and mean arterial pressure (r = 0.08, P = 0.21) were weak and
      nonsignificant. No associations were found between facet block results and any
      vital sign. Six (85.7%) of 7 patients who experienced a decrease in DBP of
      greater than 7.5 mm Hg after facet block had a positive RF denervation outcome at
      3 months, compared with 43.8% who did not (odds ratio, 7.52; 95% confidence
      interval, 0.84-363.8; P = 0.049). A classification tree based on significant
      decrease in DBP, pain duration, and baseline NRS pain score showed a 76.7%
      (range, 65.8%-86.3%) accuracy rate. CONCLUSIONS: Although a decrease in DBP of
      more than 7.5 mm Hg had 97.3% specificity and 85.7% positive predictive value for
      predicting positive RF ablation outcomes, the low negative predictive value
      (56.3%) precludes its use as a solitary screening tool. An algorithm based on
      age, baseline NRS pain score, and a significant decrease in DBP was able to
      predict 76.7% (range, 65.8%-86.3%) of RF denervation outcomes.

PMID- 24918332
TI  - Neural blockade for persistent pain after breast cancer surgery.
AB  - Persistent pain after breast cancer surgery is predominantly a neuropathic pain
      syndrome affecting 25% to 60% of patients and related to injury of the
      intercostobrachial nerve, intercostal nerves, and other nerves in the region.
      Neural blockade can be useful for the identification of nerves involved in
      neuropathic pain syndromes or to be used as a treatment in its own right. The
      purpose of this review was to examine the evidence for neural blockade as a
      potential diagnostic tool or treatment for persistent pain after breast cancer
      surgery. In this systematic review, we found only 7 studies (n = 135) assessing
      blocks directed at 3 neural structures-stellate ganglion, paravertebral plexus,
      and intercostal nerves-but none focusing on the intercostobrachial nerve. The
      quality of the studies was low and efficacy inconclusive, suggesting a need for
      well-designed, high-quality studies for this common clinical problem. 

PMID- 24918333
TI  - Comparison between digital subtraction angiography and real-time fluoroscopy to
      detect intravascular injection during lumbar transforaminal epidural injections.
AB  - BACKGROUND AND OBJECTIVE: Infrequent but serious complications of transforaminal
      epidural steroid injection (TFESI) are thought to be due to inadvertent
      intravascular injection (embolization of corticosteroid particulates via the
      vertebral or thoracolumbar radiculomedullary arteries). Recent studies suggest
      that real-time fluoroscopy often fails to detect intravascular injection and that
      digital subtraction angiography (DSA) may help reduce the incidence of accidental
      vascular injection. The goal of this prospective study was to evaluate the
      sensitivity of real-time fluoroscopy versus DSA in detecting intravascular
      injection during TFESI. METHODS: From September 2012 to July 2013, 239
      consecutive patients were enrolled and received 249 fluoroscopically guided TFESI
      using the classic technique by one physician. We collected data of patient
      demographics, reason for TFESI, occurrence of accidental intravascular injection
      based on real-time fluoroscopic images and DSA, and spinal levels at which TFESI
      was performed. Intravascular spread was assessed initially using real-time
      fluoroscopy and subsequently with DSA. RESULTS: The overall incidence of
      intravascular injection was 12.4% (31/249). Real-time fluoroscopy failed to
      detect 9 cases of intravascular injections that were subsequently detected by DSA
      (real-time fluoroscopy sensitivity, 71.0%). CONCLUSIONS: Digital subtraction
      angiography is superior to real-time fluoroscopy for detecting intravascular
      injections.

PMID- 24918334
TI  - Asleep versus awake: does it matter?: Pediatric regional block complications by
      patient state: a report from the Pediatric Regional Anesthesia Network.
AB  - BACKGROUND AND OBJECTIVES: The impact of the patient state at time of placement
      of regional blocks on the risk of complications is unknown. Current opinion is
      based almost entirely on case reports, despite considerable interest in the
      question. Analyzing more than 50,000 pediatric regional anesthesia blocks from an
      observational prospective database, we determined the rate of adverse events in
      relation to the patient's state at the time of block placement. Primary outcomes
      considered were postoperative neurologic symptoms (PONSs) and local anesthetic
      systemic toxicity (LAST). Secondary outcome was extended hospital stay due to a
      block complication. METHODS: The Pediatric Regional Anesthesia Network is a multi
      institutional research consortium that was created with an emphasis on rigorous,
      prospective, and complete data collection including a data validation and audit
      process. For the purpose of the analysis, blocks were divided in major groups by
      single injection versus continuous and by block location. Rates were determined
      in aggregate for these groups and classified further based on the patient's state
      (general anesthesia [GA] without neuromuscular blockade [NMB], GA with NMB,
      sedated, and awake) at the time of block placement. RESULTS: Postoperative
      neurological symptoms occurred at a rate of 0.93/1000 (confidence interval [CI],
      0.7-1.2) under GA and 6.82/1000 (CI, 4.2-10.5) in sedated and awake patients. The
      only occurrence of PONSs lasting longer than 6 months (PONSs-L) was a small
      sensory deficit in a sedated patient (0.019/1000 [CI, 0-0.1] for all, 0.48/1000
      [CI, 0.1-2.7] for sedated patients). There were no cases of paralysis. There were
      5 cases of LAST or 0.09/1000 (CI, 0.03-0.21). The incidence of LAST in patients
      under GA (both with and without NMB) was 0.08/1000 (CI, 0.02-0.2) and 0.34/1000
      (CI, 0-1.9) in awake/sedated patients. Extended hospital stays were described 18
      times (0.33/1000 [CI, 0.2-0.53]). The rate for patients under GA without NMB was
      0.29/1000 (CI, 0.13-0.48); GA with NMB, 0.29/1000 (CI, 0.06-0.84); sedated,
      1.47/1000 (CI, 0.3-4.3); and awake, 1.15/1000 (CI, 0.02-6.4). CONCLUSIONS: The
      placement of regional anesthetic blocks in pediatric patients under GA is as safe
      as placement in sedated and awake children. Our results provide the first
      prospective evidence for the pediatric anesthesia community that the practice of
      placing blocks in anesthetized patients should be considered safe and should
      remain the prevailing standard of care. Prohibitive recommendations based on
      anecdote and case reports cannot be supported.

PMID- 24918335
TI  - Spinal anesthesia does not impact prostate cancer recurrence in a cohort of men
      undergoing radical prostatectomy: an observational study.
AB  - BACKGROUND AND OBJECTIVES: Prior studies suggest a possible association between
      the use of neuraxial-general anesthesia and a decrease in prostate cancer
      recurrence after radical prostatectomy. We examine the correlation of a spinal
      anesthesia-only technique on prostate cancer recurrence. METHODS: Charts from
      consecutive radical prostatectomy patients of 3 experienced urologists from
      January 1999 to December 2005 were reviewed. In addition to the usual clinical
      and pathologic predictors of disease recurrence, patient records were queried for
      the type of anesthesia (general vs spinal) performed. A Cox proportional hazards
      model was used to determine the statistical significance of predictors of
      biochemical recurrence. RESULTS: A total of 1964 patients-1166 and 798 receiving
      spinal with sedation or general anesthesia, respectively-had complete
      preoperative and follow-up data. In univariate proportional hazards analysis, the
      use of general anesthesia was associated with a trend toward an increased risk of
      biochemical recurrence when compared with the use of spinal anesthesia (hazard
      ratio, 1.29; 95% confidence interval, 0.99-1.66; P = 0.053). In multivariable
      analysis, the effect size (hazard ratio, 1.10; 95% confidence interval, 0.85
      1.42; P = 0.458) was diminished by clinical and pathologic variables.
      CONCLUSIONS: This was a retrospective study of patients with prostate cancer who
      have undergone radical prostatectomy during a time period when the practice of
      anesthesia for prostatectomy at our institution was transitioned from spinal to
      general anesthesia. In our study, when controlling for other predictors of
      advanced prostate cancer, the type of anesthetic given during prostatectomy had
      no effect on the risk of biochemical recurrence.

PMID- 24918336
TI  - Hsp90 picks PIKKs via R2TP and Tel2.
AB  - Phosphatidylinositol-3 kinase-like kinases (PIKKs) are dependent on Hsp90 for
      their activation via the R2TP complex and Tel2. In this issue of Structure, Pal
      and colleagues present the molecular mechanism by which PIKKs are recruited to
      Hsp90. 

PMID- 24918337
TI  - Single-molecule choreography between telomere proteins and G quadruplexes.
AB  - Telomeric DNA binds proteins to protect chromosome ends, but it also adopts G
      quadruplex (GQ) structures. Two new studies by Hwang and colleagues (in this
      issue of Structure) and Ray and colleagues (published elsewhere) use single
      molecule imaging to reveal how GQs affect the binding of different telomere
      associated proteins. The data suggest that GQs play important roles in regulating
      accessibility of telomeres. 

PMID- 24918338
TI  - Hopeful (protein InDel) monsters?
AB  - In this issue of Structure, Arpino and colleagues describe in atomic detail how a
      protein stomachs a deletion within a helix, an event that rarely occurs in nature
      or in the lab. Can insertions and deletions (InDels) trigger dramatic structural
      transitions? 

PMID- 24918339
TI  - Phonons and hybrid modes in the high and low temperature far infrared dynamics of
      hexagonal TmMnO3.
AB  - We report on temperature dependent TmMnO3 far infrared emissivity and
      reflectivity spectra from 1910 K to 4 K. At the highest temperature the number of
      infrared bands is lower than that predicted for centrosymmetric P63/mmc
      (D(4)(6h)) (Z = 2) space group due to high temperature anharmonicity and possible
      defect induced bitetrahedra misalignments. On cooling, at ~1600 +/- 40 K, TmMnO3
      goes from non-polar to an antiferroelectric-ferroelectric polar phase reaching
      the ferroelectric onset at ~700 K. Room temperature reflectivity is fitted using
      19 oscillators and this number of phonons is maintained down to 4 K. A weak
      phonon anomaly in the band profile at 217 cm(-1) (4 K) suggests subtle Rare Earth
      magneto-electric couplings at ~TN and below. A low energy collective excitation
      is identified as a THz instability associated with room temperature eg electrons
      in a d-orbital fluctuating environment. It condenses into two modes that emerge
      pinned to the E-type antiferromagnetic order hardening simultaneously down to 4
      K. They obey power laws with TN as the critical temperature and match known zone
      center magnons. The one peaking at 26 cm(-1), with critical exponent beta=0.42 as
      for antiferromagnetic order in a hexagonal lattice, is dependent on the Rare
      Earth ion. The higher frequency companion at ~50 cm(-1), with beta=0.25, splits
      at ~TN into two peaks. The weaker band of the two is assimilated to the upper
      branch of the gap opening in the transverse acoustical (TA) phonon branch
      crossing the magnetic dispersion found in YMnO3. (Petit et al 2007 Phys. Rev.
      Lett. 99 266604). The stronger second band at ~36 cm(-1) corresponds to the lower
      branch of the TA gap. We assign both excitations as zone center magneto-electric
      hybrid quasiparticles, concluding that in NdMnO3 perovskite the equivalent
      picture corresponds to an instability which may be driven by an external field to
      transform NdMnO3 into a multiferroic compound by perturbation enhancing the TA
      phonon-magnetic correlation.

PMID- 24918340
TI  - Intranasal insulin restores insulin signaling, increases synaptic proteins, and
      reduces Abeta level and microglia activation in the brains of 3xTg-AD mice.
AB  - Decreased brain insulin signaling has been found recently in Alzheimer's disease
      (AD). Intranasal administration of insulin, which delivers the drug directly into
      the brain, improves memory and cognition in both animal studies and small
      clinical trials. However, the underlying mechanisms are unknown. Here, we treated
      9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily
      intranasal administration of insulin for seven days and then studied brain
      abnormalities of the mice biochemically and immunohistochemically. We found that
      intranasal insulin restored insulin signaling, increased the levels of synaptic
      proteins, and reduced Abeta40 level and microglia activation in the brains of
      3xTg-AD mice. However, this treatment did not affect the levels of glucose
      transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a
      mechanistic insight into the beneficial effects of intranasal insulin treatment
      and support continuous clinical trials of intranasal insulin for the treatment of
      AD. 

PMID- 24918343
TI  - Synthesis and biological evaluation of some new amide moiety bearing quinoxaline
      derivatives as antimicrobial agents.
AB  - In this study, we aimed to synthesize some new quinoxaline derivatives bearing
      amide moiety and to evaluate their antimicrobial activity. A set of 16 novel
      compounds of N-[2,3-bis(4-methoxy/methylphenyl)quinoxalin-6-yl]-substituted
      benzamide derivatives were synthesized by reacting 2,3-bis(4-methoxyphenyl)-6
      aminoquinoxaline or 2,3-bis(4-methylphenyl)-6-aminoquinoxaline with benzoyl
      chloride derivatives in tetrahydrofuran and investigated for their antimicrobial
      activity. The structures of the obtained final compounds were confirmed by
      spectral data (IR, (1)H-NMR, (13)C-NMR and MS). The antimicrobial activity of the
      compounds were determined by using the microbroth dilution method. Antimicrobial
      activity results revealed that synthesized compounds exhibited remarkable
      activity against Candida krusei (ATCC 6258) and Candida parapsilosis (ATCC
      22019). 

PMID- 24918341
TI  - Intrathecal infusion of BMAA induces selective motor neuron damage and
      astrogliosis in the ventral horn of the spinal cord.
AB  - The neurotoxin beta-N-methylamino-l-alanine (BMAA) was first identified as a
      "toxin of interest" in regard to the amyotrophic lateral sclerosis-Parkinsonism
      Dementia Complex of Guam (ALS/PDC); studies in recent years highlighting
      widespread environmental sources of BMAA exposure and providing new clues to
      toxic mechanisms have suggested possible relevance to sporadic ALS as well.
      However, despite clear evidence of uptake into tissues and a range of toxic
      effects in cells and animals, an animal model in which BMAA induces a
      neurodegenerative picture resembling ALS is lacking, possibly in part reflecting
      limited understanding of critical factors pertaining to its absorption,
      biodistribution and metabolism. To bypass some of these issues and ensure
      delivery to a key site of disease pathology, we examined effects of prolonged
      (30day) intrathecal infusion in wild type (WT) rats, and rats harboring the
      familial ALS associated G93A SOD1 mutation, over an age range (80+/-2 to 110+/
      2days) during which the G93A rats are developing disease pathology yet remain
      asymptomatic. The BMAA exposures induced changes that in many ways resemble those
      seen in the G93A rats, with degenerative changes in ventral horn motor neurons
      (MNs) with relatively little dorsal horn pathology, marked ventral horn
      astrogliosis and increased 3-nitrotyrosine labeling in and surrounding MNs, a
      loss of labeling for the astrocytic glutamate transporter, GLT-1, surrounding
      MNs, and mild accumulation and aggregation of TDP-43 in the cytosol of some
      injured and degenerating MNs. Thus, prolonged intrathecal infusion of BMAA can
      reproduce a picture in spinal cord incorporating many of the pathological
      hallmarks of diverse forms of human ALS, including substantial restriction of
      overt pathological changes to the ventral horn, consistent with the possibility
      that environmental BMAA exposure could be a risk factor and/or contributor to
      some human disease. 

PMID- 24918344
TI  - Diclofenac-Choline Antioxidant Activity Investigated by means of Luminol
      Amplified Chemiluminescence of Human Neutrophil Bursts and Electron Paramagnetic
      Resonance Spectroscopy.
AB  - A new diclofenac salt called diclofenac-choline (DC) has recently been proposed
      for the symptomatic treatment of oropharyngeal inflammatory processes and pain
      because its greater water solubility allows the use of high concentrations, which
      are useful when the contact time between the drug and the oropharyngeal mucosa is
      brief, as in the case of mouthwashes or spray formulations. The antioxidant
      activity of DC has not yet been investigated, and so the aim was to use luminol
      amplified-chemiluminescence (LACL) to verify whether various concentrations of DC
      (1.48, 0.74 and 0.37 mg/mL for incubation times of 2, 4 and 8 min) interfere with
      oxygen and nitrogen radicals during the course of human neutrophils respiratory
      bursts; electron paramagnetic resonance (EPR) spectroscopy was used to
      investigate its direct antiradical (scavenger) activity. The EPR findings showed
      that DC has concentration-dependent scavenging activity against the ABTS, the
      DPPH, and the hydroxyl radicals, but no activity on superoxide anion, as has been
      previously reported in the case of other NSAIDs. LACL revealed an inhibitory
      effect that was statistically significant after only 2 min of incubation, and
      similar after 4 and 8 min. The effects on the peroxynitrite radical paralleled
      those observed in the previous test. High concentrations and short incubation
      times showed that there is no interference on PMN viability, and so the
      inhibitory findings must be attributed to the effect of the drug. The anti
      inflammatory effects of DC cannot be attributed solely to the inhibition of
      prostaglandin synthesis, but its effects on free radicals and neutrophil bursts
      suggest that they may contribute to its final therapeutic effect.

PMID- 24918342
TI  - Epicutaneous Immunotherapy for Aeroallergen and Food Allergy.
AB  - IgE-mediated allergies today affect up to 30 % of the population in
      industrialized countries. Allergen immunotherapy is the only disease-modifying
      treatment option with a long-term effect. However, very few patients (<5 %)
      choose immunotherapy, due to the long treatment duration (between 3-5 years) and
      possible local and systemic allergic side effects of the allergen
      administrations. The latter occur when an allergen accidentally reaches the blood
      circulation. Therefore, the ideal application route for allergen immunotherapy
      should be characterized by two hallmarks: firstly, by a high number of potent
      antigen-presenting cells, which enhance efficacy and thus shorten treatment
      duration. Secondly, the allergen administration site is ideally non-vascularized,
      so that inadvertent systemic distribution of the allergen and consequent systemic
      allergic side effects are minimized. The epidermis contains high numbers of
      potent antigen-presenting Langerhans cells and, as an epithelium, is non
      vascularized. Therefore, the epidermis represents an interesting administration
      route. Historical evidence for the clinical efficacy of epicutaneous allergy
      immunotherapy (EPIT) has now been strengthened by a number of recent double
      blinded placebo-controlled clinical trials performed by independent groups. We
      review the immunological rationale, history and clinical experience with
      epicutaneous allergy immunotherapy.

PMID- 24918345
TI  - Endothelin receptor inhibition with bosentan delays onset of liver injury in
      streptozotocin-induced diabetic condition.
AB  - BACKGROUND: This study was designed to investigate the protective effects of
      bosentan an orally active non-peptide mixed ETA/ETB receptor antagonist, on liver
      injury in streptozotocin-induced diabetic rats. METHODS: 24 Albino-Wistar rats
      were randomly divided into 4 groups: healthy (Group 1), diabetic (Group 2) (60
      mg/kg of streptozotocin i.p.), diabetic treated with bosentan 50 mg/kg (Group 3)
      and diabetic treated with bosentan 100 mg/kg (Group 4). The treatment of bosentan
      was initiated after streptozocin injection and continued for 60 days. RESULTS:
      Liver from diabetic rats showed significant increase in malondialdehyde (MDA)
      level and significant decrease in glutathione (GSH), and superoxide dismutase
      (SOD) activity. Endothelin (ET-1), tumor necrosis factor (TNF-alpha) and
      transforming growth factor beta (TGF-beta) gene expression significantly
      increased in the diabetic groups in the rat liver tissue. Bosentan treatment
      showed a significant up-regulatory effect on ET-1, TNF-alpha and TGF-beta mRNA
      expression. Results from histopathological evaluation of the liver were in
      accordance with our biochemical and molecular results. CONCLUSIONS: These data
      provide clear evidence that bosentan treatment is associated with promising
      hepatoprotective effect against diabetes-induced liver damage via reduction of
      cell inflammation and oxidative damage. These data suggest that ET receptors may
      be an important actor in diabetes-related liver damage, and blockage of these
      receptors may become a target for preventing diabetic complications in the
      future.

PMID- 24918346
TI  - Genistein prevents cadmium-induced neurotoxic effects through its antioxidant
      mechanisms.
AB  - INTRODUCTION: Cadmium-induced neurotoxic effects are mediated through adverse
      oxidative stress and calcium signaling. Genistein, a phytoestrogen is a potent
      antioxidant and exhibits property to cross blood-brain barrier. METHODS:
      Experimental model of cadmium-induced neurotoxic effects were induced by
      treatment with cadmium (5 mg/kg) for 28 days in wistar rats. For determining the
      protective effect, genistein was administered at a dose of (10 mg/kg) for 7 days
      followed by cadmium treatment for 28 days. Serum and tissues were analyzed for
      various oxidative stress markers such as total antioxidant capacity, total
      oxidant levels, non-enzymic antioxidants, enzymic antioxidants, lipid peroxide
      levels and protein carbonyl content. RESULTS: The results showed significant
      increase in the oxidative stress markers during cadmium treatment was attenuated
      in rats treated with genistein followed by cadmium treatment. In addition,
      cadmium induced alterations and activities of ATPase were significantly restored
      by genistein treatment. CONCLUSION: The present study observations show promising
      results of genistein against cadmium-induced neurotoxic effects in wistar rats.
      Thus its potent antioxidant and cytoprotective effects could act as potent
      therapeutic agent against various neuro-degenerative diseases involving oxidative
      stress as primary mechanism.

PMID- 24918347
TI  - Determination of SK3497 in rat plasma and its application in a pharmacokinetic
      study of SK3497.
AB  - In this study, a sensitive and reliable method for the quantitation of SK3497 in
      rat plasma was developed and validated using high performance liquid
      chromatography. The plasma samples were prepared by deproteinization, and
      sildenafil was used as an internal standard. Chromatographic separation was
      achieved using a reversed-phase (C18) column. The mobile phase, 0.02 M ammonium
      acetate buffer:acetonitrile (45:55, v/v), was run at a flow rate of 1.0 mL/min,
      and the column eluent was monitored using an ultraviolet detector at 254 nm at
      room temperature. The retention times of sildenafil (an internal standard), and
      SK3497 were approximately 5.6 and 8.3 min, respectively. The detection limit of
      SK3497 in rat plasma was 0.03 MUg/mL. Pharmacokinetic parameters of SK3497 was
      evaluated after intravenous (i. v.; at doses of 15 mg/kg) and oral (p.o.; at
      doses of 30 mg/kg) administration of SK3497 in rats. After p.o. administration
      (30 mg/kg) of SK3497, F-value was approximately 53.0%. The protein binding of
      SK3497 to 4% human serum albumin were also described. 

PMID- 24918348
TI  - Synthesis and evaluation of anti-acetylcholinesterase activity of some
      benzothiazole based new piperazine-dithiocarbamate derivatives.
AB  - In this present study some benzothiazole derivatives bearing piperazine and
      thiocarbamate moieties were synthesized and their potential anticholinesterase
      properties were investigated. A set of 30 new compounds of 2-[(6-substituted
      benzothiazol-2-yl)amino]-2-oxoethyl 4-substituted piperazine-1-carbodithioate
      derivatives were synthesized by reacting 2-chloro-N-(6-substituted benzothiazole
      2-yl)acetamide derivatives derivatives and sodium salts of appropriate N,N
      disubstituted dithiocarbamic acids in acetone. The structures of the obtained
      compounds were elucidated using FT-IR, (1)H-NMR and MS spectral data and
      elemental analyses result. Each derivative was evaluated for its ability to
      inhibit acetylcholinesterase (AChE) using a modificated Ellman's
      spectrophotometric method. Some of the compounds can be identified as
      anticholinesterase agents due to their inhibitory effect when compared with
      Donepezil. Compounds with dimethylamino ethyl or dimethylamino propyl
      substituents were defined as the anticholinesterase active compounds. 

PMID- 24918349
TI  - Comparative study on effects of nebulized and oral salbutamol on a cecal ligation
      and puncture-induced sepsis model in rats.
AB  - AIM: The present study aimed to compare the effects of different routes of
      salbutamol administration (oral and nebulized) at different doses in a cecal
      ligation and puncture-induced (CLP-induced) sepsis model of rats. METHODS: Rats
      were separated into 8 groups: 1) sham, 2) sham+4 mg/kg oral salbutamol, 3) sham+6
      min 2 mg/ml nebulized salbutamol, 4) CLP, 5) CLP+2 mg/kg oral salbutamol, 6)
      CLP+4 mg/kg oral salbutamol, 7) CLP+3 min 2 mg/ml nebulized salbutamol, 8) CLP+6
      min 2 mg/ml nebulized salbutamol. Subsequently, sepsis was induced by CLP through
      16 h. RESULTS: CLP-induced sepsis increased serum cytokine levels (TNF-alpha, IL
      1beta, and IL-6), increased tissue oxidative stress (8-Isoprosraglandin F2alpha),
      decreased antioxidant parameters (SOD, GSH), and increased lung injury by
      inflammatory cell accumulation. CONCLUSION: This study showed for the first time
      that oral administration of salbutamol exerted protective effects on CLP-induced
      sepsis and related lung injury in rats. We conclude that despite the greater side
      effects of oral salbutamol, it should be considered for administration in oral
      form due to its systemic effectiveness during septic conditions in emergency
      settings.

PMID- 24918350
TI  - [First case of phaeohyphomycosis due to Pleurostoma ootheca in a kidney
      transplant recipient in Martinique (French West Indies)].
AB  - Phaeohyphomycosis is a group of superficial and deep infections due to
      dematiaceous fungi. They are most common in tropical environments, especially in
      immunocompromised hosts. We describe the first case of phaeohyphomycosis due to
      Pleurostoma ootheca in a kidney transplant recipient in Martinique (French West
      Indies). A 59-year-old man with a kidney graft, treated with mycophenolate
      mofetil, tacrolimus, and prednisone, presented suppurative tumefaction of the
      left ankle. Cutaneous and osseous phaeohyphomycosis caused by P. ootheca was
      diagnosed, based on mycological, histological, and radiological testing. The
      patient's condition improved with posaconazole treatment. P. ootheca is a known
      environmental fungus. Immunocompromised hosts are more vulnerable to many
      infections, due to opportunistic pathogens. Bacteriological, histological, and
      mycological testing is required for accurate diagnosis and appropriate treatment.
      Treatment is not well defined and usually relies on antifungal agents or surgical
      resection or both. An important point to consider is that azole antifungal agents
      may cause major drug-drug interactions with immunosuppressive agents such as
      tracrolimus. 

PMID- 24918351
TI  - Traditional Chinese exercises for pulmonary rehabilitation: evidence from a
      systematic review.
AB  - BACKGROUND: Qigong (QG) and tai chi (TC), alternative forms of exercise based on
      traditional Chinese medicine, are reported to be beneficial to patients with
      chronic obstructive pulmonary disease (COPD). This systematic review analyzed the
      evidence and made recommendations for clinical applications and future research.
      METHODS: Key words "qigong," "tai chi," "COPD," and "randomized controlled trial"
      or corresponding terms in Chinese were searched using MEDLINE, EMBASE, and 3
      Chinese databases. Randomized controlled trials (RCTs) on QG and/or TC for
      patients with COPD were included. The quality of each RCT was appraised using the
      Physiotherapy Evidence Database (PEDro) scale. Outcome variables that were
      reported by greater than one-third of the RCTs were pooled for analysis. RESULTS:
      A total of 37 RCTs were identified, with 12 matching the inclusion criteria. The
      average PEDro score was 5.25, indicating that limitations were noted in the
      methodology. Only forced expiratory volume in the first second of
      expiration/forced vital capacity ratio and the 6-Minute Walk Test (6MWT) distance
      were common outcome measures in greater than one-third of the RCTs. The weighted
      mean differences and the 95% CI estimation for mean gains in forced expiratory
      volume in the first second of expiration/forced vital capacity ratio and mean
      gains in 6MWT distance between QG/TC and conventional exercise groups were 0.62
      (95% CI, 0.30-0.93) and 12.18 (95% CI, 10.32-14.05) m, respectively. The
      corresponding values between QG/TC and no exercise groups were 2.90 (95% CI, 2.37
      3.43) and 37.77 (95% CI, 35.42-40.12) m, respectively. CONCLUSIONS: This
      systematic review supports the therapeutic value of QG/TC in patients with COPD
      and highlights areas for future research.

PMID- 24918352
TI  - Repeatability of usual and fast walking speeds in patients with chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Evaluation of the role of walking speeds in chronic obstructive
      pulmonary disease (COPD) should be preceded by an assessment of its
      repeatability. This study aimed to establish the repeatability of the usual
      (susual) and fast (sfast) walking speeds among patients with stable COPD and
      determine the accuracy of manual measurement. METHODS: Participants demonstrated
      their susual and sfast over 10 m with speed calculated using a stopwatch; the
      accuracy was confirmed with optical sensors. The walks were repeated after a 5
      minute rest; the session was repeated on 2 subsequent days. The coefficient of
      repeatability (CR) was calculated for both speeds, and their stability over days
      was determined. RESULTS: A total of 29 participants (forced expiratory volume in
      1 second (FEV1) = 43 +/- 25% predicted; FEV1/forced vital capacity (FVC) = 41 +/-
      13%; susual = 60.3 +/- 11 m.min; sfast = 74.3 +/- 11.5 m.min) completed the
      study. The CRs for the susual and sfast were 7.5 (95% CI: 5.0-10.0) and 7.1 (95%
      CI: 4.8-9.4) m.min, respectively. There was a small increase in the susual (5%; P
      < .001) on the second trial of every day and between successive days (5%; P <
      .001); the sfast was not different between trials (P = .09) and increased only
      between day 1 and day 2 (4%; P < .0001). There was no difference between the
      stopwatch and the sensor determined susual (-0.5 [95% CI: -1.1 to 0.1] m.min; P =
      .12). The small difference (-2.1 [95% CI: -2.7 to -1.5] m.min; P = .0001) between
      the methods for sfast was within the CR of the sfast. CONCLUSIONS: In patients
      with moderate to severe COPD, repeated measures of the susual and sfast using a
      stopwatch support the use of these tests for simple, quick assessments of
      disability.

PMID- 24918353
TI  - Endocytosis: Bend it like galectin 3.

PMID- 24918354
TI  - Larger CO2 source at the equatorial Pacific during the last deglaciation.
AB  - While biogeochemical and physical processes in the Southern Ocean are thought to
      be central to atmospheric CO2 rise during the last deglaciation, the role of the
      equatorial Pacific, where the largest CO2 source exists at present, remains
      largely unconstrained. Here we present seawater pH and pCO2 variations from
      fossil Porites corals in the mid equatorial Pacific offshore Tahiti based on a
      newly calibrated boron isotope paleo-pH proxy. Our new data, together with
      recalibrated existing data, indicate that a significant pCO2 increase (pH
      decrease), accompanied by anomalously large marine (14)C reservoir ages, occurred
      following not only the Younger Dryas, but also Heinrich Stadial 1. These findings
      indicate an expanded zone of equatorial upwelling and resultant CO2 emission,
      which may be derived from higher subsurface dissolved inorganic carbon
      concentration.

PMID- 24918355
TI  - Convergent heteroditopic cyclo[6]aramides as macrocyclic ion-pair receptors for
      constructing [2]pseudorotaxanes.
AB  - A strategy of using amide groups as the only functionality was developed to
      construct convergent heteroditopic cyclo[6]aramides that are able to strongly
      bind dibutylammonium chloride in chloroform (>10(5) M(-1)), leading to the
      formation of [2]pseudorotaxanes. 

PMID- 24918356
TI  - Plasmon-assisted radiolytic energy conversion in aqueous solutions.
AB  - The field of conventional energy conversion using radioisotopes has almost
      exclusively focused on solid-state materials. Herein, we demonstrate that liquids
      can be an excellent media for effective energy conversion from radioisotopes. We
      also show that free radicals in liquid, which are continuously generated by beta
      radiation, can be utilized for electrical energy generation. Under beta
      radiation, surface plasmon obtained by the metallic nanoporous structures on TiO2
      enhanced the radiolytic conversion via the efficient energy transfer between
      plasmons and free radicals. This work introduces a new route for the development
      of next-generation power sources.

PMID- 24918357
TI  - Large magnetoelectric coupling in magnetically short-range ordered Bi5Ti3FeO15
      film.
AB  - Multiferroic materials, which offer the possibility of manipulating the magnetic
      state by an electric field or vice versa, are of great current interest. However,
      single-phase materials with such cross-coupling properties at room temperature
      exist rarely in nature; new design of nano-engineered thin films with a strong
      magneto-electric coupling is a fundamental challenge. Here we demonstrate a
      robust room-temperature magneto-electric coupling in a bismuth-layer-structured
      ferroelectric Bi5Ti3FeO15 with high ferroelectric Curie temperature of ~1000 K.
      Bi5Ti3FeO15 thin films grown by pulsed laser deposition are single-phase layered
      perovskit with nearly (00l)-orientation. Room-temperature multiferroic behavior
      is demonstrated by a large modulation in magneto-polarization and magneto
      dielectric responses. Local structural characterizations by transmission electron
      microscopy and Mossbauer spectroscopy reveal the existence of Fe-rich
      nanodomains, which cause a short-range magnetic ordering at ~620 K. In
      Bi5Ti3FeO15 with a stable ferroelectric order, the spin canting of magnetic-ion
      based nanodomains via the Dzyaloshinskii-Moriya interaction might yield a robust
      magneto-electric coupling of ~400 mV/Oe.cm even at room temperature.

PMID- 24918358
TI  - Further insights into brevetoxin metabolism by de novo radiolabeling.
AB  - The toxic dinoflagellate Karenia brevis, responsible for early harmful algal
      blooms in the Gulf of Mexico, produces many secondary metabolites, including
      potent neurotoxins called brevetoxins (PbTx). These compounds have been
      identified as toxic agents for humans, and they are also responsible for the
      deaths of several marine organisms. The overall biosynthesis of these highly
      complex metabolites has not been fully ascertained, even if there is little doubt
      on a polyketide origin. In addition to gaining some insights into the metabolic
      events involved in the biosynthesis of these compounds, feeding studies with
      labeled precursors helps to discriminate between the de novo biosynthesis of
      toxins and conversion of stored intermediates into final toxic products in the
      response to environmental stresses. In this context, the use of radiolabeled
      precursors is well suited as it allows working with the highest sensitive
      techniques and consequently with a minor amount of cultured dinoflagellates. We
      were then able to incorporate [U-14C]-acetate, the renowned precursor of the
      polyketide pathway, in several PbTx produced by K. brevis. The specific
      activities of PbTx-1, -2, -3, and -7, identified by High-Resolution Electrospray
      Ionization Mass Spectrometer (HRESIMS), were assessed by HPLC-UV and highly
      sensitive Radio-TLC counting. We demonstrated that working at close to natural
      concentrations of acetate is a requirement for biosynthetic studies, highlighting
      the importance of highly sensitive radiolabeling feeding experiments.
      Quantification of the specific activity of the four, targeted toxins led us to
      propose that PbTx-1 and PbTx-2 aldehydes originate from oxidation of the primary
      alcohols of PbTx-7 and PbTx-3, respectively. This approach will open the way for
      a better comprehension of the metabolic pathways leading to PbTx but also to a
      better understanding of their regulation by environmental factors.

PMID- 24918359
TI  - Designing vaccines to neutralize effective toxin delivery by enterotoxigenic
      Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) are a leading cause of diarrheal illness
      in developing countries. Despite the discovery of these pathogens as a cause of
      cholera-like diarrhea over 40 years ago, and decades of vaccine development
      effort, there remains no broadly protective ETEC vaccine. The discovery of new
      virulence proteins and an improved appreciation of the complexity of the
      molecular events required for effective toxin delivery may provide additional
      avenues to pursue in development of an effective vaccine to prevent severe
      diarrhea caused by these important pathogens. 

PMID- 24918361
TI  - Prediction factors for failure to seek treatment following traumatic dental
      injuries to primary teeth.
AB  - The objective of this study was to evaluate prediction factors for failure to
      seek treatment following a traumatic dental injury (TDI) to primary teeth among
      preschool children in the city of Campina Grande, Brazil. A cross-sectional study
      was carried out involving 277 children 3 to 5 years of age, with TDI, enrolled in
      public and private preschools. Parents filled out a form addressing demographic
      data and whether or not they had sought treatment. Clinical examinations were
      performed by three dentists who had undergone a calibration exercise (Kappa: 0.85
      to 0.90) for the evaluation of TDI. Bivariate and multivariate Poisson regression
      models were constructed (alpha=5%). Enamel fracture was the most prevalent type
      of TDI (48.7%) and the upper central incisors were the most affected teeth
      (88.4%). The frequency of seeking dental treatment was low (9.7%). The following
      variables were associated with failure to seek treatment following TDI: a
      household income greater than one minimum wage (PR=1.170; 95%CI 1.018-1.341),
      parents/caregivers' perception of a child's oral health as poor (PR=1.100; 95%CI
      1.026-1.176), and the non-perception of TDI by parents/caregivers (PR=1.250;
      95%CI 1.142-1.360). In the present study, the frequency of seeking treatment
      following TDI was low, and parents/caregivers with a higher income, a poor
      perception of their child's oral health and a lack of awareness regarding the
      trauma were more likely to fail to seek treatment following TDI to primary teeth.

PMID- 24918362
TI  - Reliability and validity of MINCIR scale for methodological quality in dental
      therapy research.
AB  - The clinical paradigm of evidence-based medicine requires a foundation of good
      quality research upon which clinical and epidemiological decisions can be based.
      Several instruments have been designed to assess research quality and validated,
      though most have limitations. The MINCIR scale was designed to determine the
      methodological quality (MQ) of clinical research, its psychometric properties for
      dental research involving large-scale evaluations have not yet been determined.
      The aim of this study was to determine the validity and reliability of the MINCIR
      scale for assessment of the MQ of dental therapy studies published in journals
      indexed in Institute for Scientific Information (ISI) databases. A validation
      study was performed on a sample of 99 articles from four representative ISI
      dental journals. Criterion validity was determined in relation to level of
      evidence (LoE) classification as described by the Oxford Center for Evidence
      Based Medicine (OCEBM) ranking system, reliability was determined by calculation
      of intra-class correlation coefficient (ICC) values, and internal consistency was
      determined by calculation of Cronbach's alpha. Very good inter-observer
      reliability (ICC=0.93), excellent temporal stability (ICC=0.97), good internal
      consistency (Cronbach's alpha=0.77), and a strong (inverse) correlation with
      OCEBM LoEs (-0.807; p<.0001) were obtained. These results indicate that the
      MINCIR scale has adequate psychometric properties and therefore is a valid option
      for use in the assessment of MQ in dental therapy research articles.

PMID- 24918360
TI  - Microcystins alter chemotactic behavior in Caenorhabditis elegans by selectively
      targeting the AWA sensory neuron.
AB  - Harmful algal blooms expose humans and animals to microcystins (MCs) through
      contaminated drinking water. While hepatotoxicity following acute exposure to MCs
      is well documented, neurotoxicity after sub-lethal exposure is poorly understood.
      We developed a novel statistical approach using a generalized linear model and
      the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis
      elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure
      on AWA versus AWC sensory neuron function were determined using a chemotaxis
      assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC
      LF was more potent than MC-LR. To probe a potential role for protein phosphatases
      (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed
      to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h.
      Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect
      on function of either neuronal cell type at the concentrations tested. These
      findings suggest that MCs alter the AWA neuron at concentrations that do not
      cause AWC toxicity via mechanisms other than PP inhibition. 

PMID- 24918363
TI  - Reproducibility of a silicone-based test food to masticatory performance
      evaluation by different sieve methods.
AB  - The aim of this study was to evaluate the reproducibility of the condensation
      silicone Optosil Comfort(r) as an artificial test food for masticatory
      performance evaluation. Twenty dentate subjects with mean age of 23.3+/-0.7 years
      were selected. Masticatory performance was evaluated using the simple (MPI), the
      double (IME) and the multiple sieve methods. Trials were carried out five times
      by three examiners: three times by the first, and once by the second and third
      examiners. Friedman's test was used to find the differences among time trials.
      Reproducibility was determined by the intra-class correlation (ICC) test
      (alpha=0.05). No differences among time trials were found, except for MPI-4 mm
      (p=0.022) from the first examiner results. The intra-examiner reproducibility
      (ICC) of almost all data was high (ICC>=0.92, p<0.001), being moderate only for
      MPI-0.50 mm (ICC=0.89, p<0.001). The inter-examiner reproducibility was high
      (ICC>0.93, p<0.001) for all results. For the multiple sieve method, the average
      mean of absolute difference from repeated measurements were lower than 1 mm. This
      trend was observed only from MPI-0.50 to MPI-1.4 for the single sieve method, and
      from IME-0.71/0.50 to IME-1.40/1.00 for the double sieve method. The results
      suggest that regardless of the method used, the reproducibility of Optosil
      Comfort(r) is high.

PMID- 24918364
TI  - Effects of stress hormones on the production of volatile sulfur compounds by
      periodontopathogenic bacteria.
AB  - Little is known about the effects of stress hormones on the etiologic agents of
      halitosis. Thus, the aim of this study was to evaluate in vitro the effects of
      adrenaline (ADR), noradrenaline (NA) and cortisol (CORT) on bacteria that produce
      volatile sulfur compounds (VSC), the major gases responsible for bad breath.
      Cultures of Fusobacterium nucleatum (Fn), Porphyromonas endodontalis (Pe),
      Prevotella intermedia (Pi) and Porphyromonas gingivalis (Pg) were exposed to 50
      uM ADR, NA and CORT or equivalent volumes of sterile water as controls for 12 and
      24 h. Growth was evaluated based on absorbance at 660 nm. Portable gas
      chromatography was used to measure VSC concentrations. Kruskal-Wallis and the
      Dunn post-hoc test were used to compare the groups. For Fn, ADR, NA and CORT
      significantly reduced bacterial growth after 12 h and 24 h (p<0.05). All the
      substances tested increased hydrogen sulfide (H2S) production (p<0.05). For Pe,
      all the substances tested reduced bacterial development after 24 h (p<0.05), and
      NA significantly increased the H2S concentration after 12 h (p<0.05). In the Pg
      and Pi cultures, no effects on bacterial growth were observed (p>0.05). In the Pi
      cultures, ADR, NA and CORT increased H2S (p<0.05). Catecholamines and cortisol
      can interfere with growth and H2S production of sub-gingival species in vitro.
      This process appears to be complex and supports the association between stress
      and the production of VSC.

PMID- 24918365
TI  - Resorption of roots of different dimension induced by different types of forces.
AB  - Root resorption is a variable to be considered in induced tooth movement (ITM).
      It is related to root morphology and alveolar bone crest, and also to the types
      of forces exerted by mechanotherapy. This histometric study evaluated the
      predominance of root resorption among roots of different dimensions, following
      ITM with different types of forces and at different time intervals. The study was
      conducted on 54 rats divided into three groups, according to the type of force:
      continuous (CF), continuous interrupted (CIF) and intermittent (IF), at periods
      of 5, 7 and 9 days. The percentage of resorption between mesiobuccal roots of
      larger dimension and intermediate roots of smaller dimension was assessed. The
      evaluations were performed on the AxioVision software, and the non-parametric
      analysis of variance for repeated measures in independent groups was further
      applied, consisting of a scheme of two factors, and complemented by the Dunn test
      at a significance level of 5%. The intermediate roots presented a higher
      percentage of resorption, which was gradual at the periods evaluated for the
      three types of forces, but mainly for CF. Comparing the intermediate roots with
      the mesiobuccal roots, there was a statistically significant difference (p<0.05)
      in the CF group at day 7 and day 9, and in the FI group, at day 9. The intragroup
      analysis evidenced a statistically significant difference (p<0.05) between the
      5th and the 9th day for the intermediate root in the CF group. The intergroup
      analysis did not reveal any statistically significant difference (p>0.05) in
      individually analyzed roots.

PMID- 24918366
TI  - Influence of surrounding wall thickness on the fatigue resistance of molars
      restored with ceramic inlay.
AB  - The purpose of this study was to evaluate the influence of buccal and lingual
      wall thickness on the fatigue resistance of molars restored with CAD/CAM ceramic
      inlays. Forty human third molars were selected and divided into 4 groups,
      according to the remaining surrounding wall thickness chosen for inlay
      preparation (n=10): G1, 2.0 mm; G2, 1.5 mm; G3, 1.0 mm; G4, 0.5 mm. All inlays
      were made from feldspathic ceramic blocks by a CAD/CAM system, and cemented
      adhesively. After 1 week stored in distilled water at 37  degrees C, the
      specimens were subjected to fatigue testing under the following protocol: 5Hz;
      pre-load of 200 N for 5,000 cycles, followed by increasing loads of 400, 600,
      800, 1000, 1200 and 1400 N for 30,000 cycles each. The specimens were cycled
      until failure or completion of 185,000 cycles. The survival rate of the groups
      was compared using the Kaplan-Meier survival curves (p>0.05). All specimens
      withstood the fatigue protocol (185,000 cycles), representing a 100% survival
      rate. The Kaplan-Meier survival curves showed no difference between groups. It
      can be concluded that the remaining tooth wall thickness did not influence the
      fatigue resistance of molars restored with CAD/CAM ceramic inlays.

PMID- 24918368
TI  - Effects of layering technique on the shade of resin overlays and the
      microhardness of dual cure resin cement.
AB  - The purpose of this study was to assess the color of layered resin overlays and
      to test the early microhardness of dual cure resin cement (DCRC) light cured
      through the layered resin overlays. Resin overlays of 1.5 mm thickness were
      fabricated with the A3 shade of Z350 (Group 1L), the A3B and A3E shades of
      Supreme XT (Group 2L), and the A3, E3, and T1 shades of Sinfony (Group 3L) using
      one, two, and three layers, respectively (n=7). Each layer of the resin overlays
      was set in equal thickness. The color of the resin overlays was measured with a
      colorimeter and compared with an A3 shade resin denture tooth. DCRC was light
      cured through the resin overlays, and the early microhardness of the DCRC was
      measured. The DeltaE value between the denture tooth and the resin overlays and
      the Vickers hardness number (VHN) of the DCRC were analyzed with one-way ANOVA
      and Tukey's HSD test. The color differences were 8.9+/-0.5, 5.3+/-1.0, and 7.3+/
      0.5 and the VHNs were 19.4+/-1.1, 21.1+/-0.9, and 29.3+/-0.6 for Groups 1L, 2L,
      and 3L, respectively. Therefore, to match the designated tooth color of resin
      inlays and to increase the early microhardness of DCRC, layered resin inlays are
      more appropriate than single-dentin-layer resin inlays. However, the translucent
      layer should be used cautiously because the color difference of resin inlays with
      a translucent layer was affected more than those without a translucent layer.

PMID- 24918367
TI  - Nifedipine-induced histological changes in the parotid glands of hypertensive
      rats.
AB  - Nifedipine is a widely used anti-anginal and anti-hypertensive agent. It is
      associated with significant gingival changes attributed more to collagen
      hyperplasia than to enhancement of protein synthesis. We investigated the
      influence of nifedipine on morphological changes in the parotid glands of rats in
      a model of hypertension. Twenty-eight male Wistar rats (8-10 weeks; 200+/-15 g)
      were divided into four groups (A-D). Hypertension was induced by surgical means
      in groups C and D. Animals in groups B and D were treated with nifedipine (0.85
      mg/kg) via a gastroesophageal catheter the day after surgery (experimental day-1)
      for 2 weeks. A significant difference was observed between the control group and
      nifedipine group and between the control group and hypertension group with regard
      to the weight of the parotid gland and its surface area. Histological findings
      demonstrated changes in the parotid glands of hypertensive animals with mild
      vessel dilatation and infiltration of inflammatory cells. These histological
      findings seemed to be due more to changes in venous function than to alterations
      in gland architecture.

PMID- 24918369
TI  - Microbiological changes after periodontal therapy in diabetic patients with
      inadequate metabolic control.
AB  - The present study investigated the effect of non-surgical periodontal treatment
      (SRP) on the composition of the subgingival microbiota of chronic periodontitis
      (CP) in individuals with type 2 diabetes (DM2) with inadequate metabolic control
      and in systemically healthy (SH) individuals. Forty individuals (20 DM2 and 20
      SH) with CP underwent full-mouth periodontal examination. Subgingival plaque was
      sampled from 4 deep sites of each individual and tested for mean prevalence and
      counts of 45 bacterial taxa by the checkerboard method. Clinical and
      microbiological assessments were performed before and 3 months after SRP. At
      baseline, those in the DM2 group presented a significantly higher percentage of
      sites with visible plaque and bleeding on probing compared with those in the SH
      group (p<0.01). Those in the DM2 group presented significantly higher levels of
      C. rectus and P. gingivalis, and lower prevalence of P. micra and S. anginosus,
      compared with those in the SH group (p<=0.001). At the 3-month visit, both groups
      showed a significant improvement in all clinical parameters (p<0.01). Those in
      the DM2 group showed significantly higher prevalence and/or levels of A.
      gerencseriae, A. naeslundii I, A. oris, A. odontolyticus, C. sputigena, F.
      periodonticum, and G. morbillorum compared with those in the SH group (p<=0.001).
      However, those in the DM2 group showed a significant reduction in the levels of
      P. intermedia, P. gingivalis, T. forsythia, and T. denticola (p<=0.001) over
      time. Those in the SRP group showed improved periodontal status and reduced
      levels of putative periodontal pathogens at 3 months' evaluation compared with
      those in the DM2 group with inadequate metabolic control.

PMID- 24918370
TI  - Effect of cleanser solutions on the color of acrylic resins associated with
      titanium and nickel-chromium alloys.
AB  - This study evaluated the effect of cleanser solutions on the color of heat
      polymerized acrylic resin (HPAR) and on the brightness of dental alloys with 180
      immersion trials. Disk-shaped specimens were made with I) commercially pure
      titanium, II) nickel-chromium-molybdenum-titanium, III) nickel-chromium
      molybdenum, and IV) nickel-chromium-molybdenum beryllium. Each cast disk was
      invested in the flasks, incorporating the metal disk into the HPAR. The specimens
      (n=5) were then immersed in solutions containing: 0.05% sodium hypochlorite,
      0.12% chlorhexidine digluconate, 0.500 mg cetylpyridinium chloride, a citric acid
      tablet, one of two different sodium perborate/enzyme tablets, and water. The
      color measurements (?E) of the HPAR were determined by a colorimeter in
      accordance with the National Bureau of Standards. The surface brightness of the
      metal was visually examined for the presence of tarnish. The results (ANOVA;
      Tukey test-alpha=0.05) show that there was a significant difference between the
      groups (p<0.001) but not among the solutions (p=0.273). The highest mean was
      obtained for group III (5.06), followed by group II (2.14). The lowest averages
      were obtained for groups I (1.33) and IV (1.35). The color changes in groups I,
      II and IV were slight but noticeable, and the color change was considerable for
      group III. The visual analysis showed that 0.05% sodium hypochlorite caused
      metallic brightness changes in groups II and IV. It can be concluded that the
      agents had the same effect on the color of the resin and that the metallic alloys
      are not resistant to the action of 0.05% sodium hypochlorite.

PMID- 24918371
TI  - CPAP, weight loss, or both for obstructive sleep apnea.
AB  - BACKGROUND: Obesity and obstructive sleep apnea tend to coexist and are
      associated with inflammation, insulin resistance, dyslipidemia, and high blood
      pressure, but their causal relation to these abnormalities is unclear. METHODS:
      We randomly assigned 181 patients with obesity, moderate-to-severe obstructive
      sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per
      liter to receive treatment with continuous positive airway pressure (CPAP), a
      weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks.
      We assessed the incremental effect of the combined interventions over each one
      alone on the CRP level (the primary end point), insulin sensitivity, lipid
      levels, and blood pressure. RESULTS: Among the 146 participants for whom there
      were follow-up data, those assigned to weight loss only and those assigned to the
      combined interventions had reductions in CRP levels, insulin resistance, and
      serum triglyceride levels. None of these changes were observed in the group
      receiving CPAP alone. Blood pressure was reduced in all three groups. No
      significant incremental effect on CRP levels was found for the combined
      interventions as compared with either weight loss or CPAP alone. Reductions in
      insulin resistance and serum triglyceride levels were greater in the combined
      intervention group than in the group receiving CPAP only, but there were no
      significant differences in these values between the combined-intervention group
      and the weight-loss group. In per-protocol analyses, which included 90
      participants who met prespecified criteria for adherence, the combined
      interventions resulted in a larger reduction in systolic blood pressure and mean
      arterial pressure than did either CPAP or weight loss alone. CONCLUSIONS: In
      adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss
      intervention did not reduce CRP levels more than either intervention alone. In
      secondary analyses, weight loss provided an incremental reduction in insulin
      resistance and serum triglyceride levels when combined with CPAP. In addition,
      adherence to a regimen of weight loss and CPAP may result in incremental
      reductions in blood pressure as compared with either intervention alone. (Funded
      by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number,
      NCT0371293 .).

PMID- 24918372
TI  - CPAP versus oxygen in obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea is associated with hypertension,
      inflammation, and increased cardiovascular risk. Continuous positive airway
      pressure (CPAP) reduces blood pressure, but adherence is often suboptimal, and
      the benefit beyond management of conventional risk factors is uncertain. Since
      intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, we
      evaluated the effects of nocturnal supplemental oxygen and CPAP on markers of
      cardiovascular risk. METHODS: We conducted a randomized, controlled trial in
      which patients with cardiovascular disease or multiple cardiovascular risk
      factors were recruited from cardiology practices. Patients were screened for
      obstructive sleep apnea with the use of the Berlin questionnaire, and home sleep
      testing was used to establish the diagnosis. Participants with an apnea-hypopnea
      index of 15 to 50 events per hour were randomly assigned to receive education on
      sleep hygiene and healthy lifestyle alone (the control group) or, in addition to
      education, either CPAP or nocturnal supplemental oxygen. Cardiovascular risk was
      assessed at baseline and after 12 weeks of the study treatment. The primary
      outcome was 24-hour mean arterial pressure. RESULTS: Of 318 patients who
      underwent randomization, 281 (88%) could be evaluated for ambulatory blood
      pressure at both baseline and follow-up. On average, the 24-hour mean arterial
      pressure at 12 weeks was lower in the group receiving CPAP than in the control
      group (-2.4 mm Hg; 95% confidence interval [CI], -4.7 to -0.1; P=0.04) or the
      group receiving supplemental oxygen (-2.8 mm Hg; 95% CI, -5.1 to -0.5; P=0.02).
      There was no significant difference in the 24-hour mean arterial pressure between
      the control group and the group receiving oxygen. A sensitivity analysis
      performed with the use of multiple imputation approaches to assess the effect of
      missing data did not change the results of the primary analysis. CONCLUSIONS: In
      patients with cardiovascular disease or multiple cardiovascular risk factors, the
      treatment of obstructive sleep apnea with CPAP, but not nocturnal supplemental
      oxygen, resulted in a significant reduction in blood pressure. (Funded by the
      National Heart, Lung, and Blood Institute and others; HeartBEAT
      ClinicalTrials.gov number, NCT01086800 .).

PMID- 24918373
TI  - Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis.
AB  - BACKGROUND: We assessed the efficacy and safety of brodalumab, a human monoclonal
      antibody against interleukin-17 receptor A (IL17RA), in a phase 2, randomized,
      double-blind, placebo-controlled study involving patients with psoriatic
      arthritis. METHODS: We randomly assigned patients with active psoriatic arthritis
      to receive brodalumab (140 or 280 mg subcutaneously) or placebo on day 1 and at
      weeks 1, 2, 4, 6, 8, and 10. At week 12, patients who had not discontinued their
      participation in the study were offered open-label brodalumab (280 mg) every 2
      weeks. The primary end point was 20% improvement in American College of
      Rheumatology response criteria (ACR 20) at week 12. RESULTS: Of the 168 patients
      who underwent randomization (57 in the brodalumab 140-mg group, 56 in the
      brodalumab 280-mg group, and 55 in the placebo group), 159 completed the double
      blind phase and 134 completed 40 weeks of the open-label extension. At week 12,
      the brodalumab 140-mg and 280-mg groups had higher rates of ACR 20 than the
      placebo group (37% [P=0.03] and 39% [P=0.02], respectively, vs. 18%); they also
      had higher rates of 50% improvement (ACR 50) (14% [P=0.05] and 14% [P=0.05] vs.
      4%). Rates of 70% improvement were not significantly higher in the brodalumab
      groups. Similar degrees of improvement were noted among patients who had received
      previous biologic therapy and those who had not received such therapy. At week
      24, ACR 20 response rates in the brodalumab 140-mg and 280-mg groups were 51% and
      64%, respectively, as compared with 44% among patients who switched from placebo
      to open-label brodalumab; responses were sustained through week 52. At week 12,
      serious adverse events had occurred in 3% of patients in the brodalumab groups
      and in 2% of those in the placebo group. CONCLUSIONS: Brodalumab significantly
      improved response rates among patients with psoriatic arthritis. Larger studies
      of longer duration are necessary to assess adverse events. (Funded by Amgen;
      ClinicalTrials.gov number, NCT01516957 .).

PMID- 24918374
TI  - Clinical practice. The child or adolescent with elevated blood pressure.

PMID- 24918375
TI  - Images in clinical medicine. Morgagnian cataract.

PMID- 24918376
TI  - Case records of the Massachusetts General Hospital. Case 18-2014. A 32-Year-old
      man with a rash, myalgia, and weakness.

PMID- 24918377
TI  - Cardiovascular morbidity and obstructive sleep apnea.

PMID- 24918378
TI  - Translating the genomic revolution - targeted genome editing in primates.

PMID- 24918379
TI  - Hemicraniectomy for middle-cerebral-artery stroke. Author reply.

PMID- 24918380
TI  - Hemicraniectomy for middle-cerebral-artery stroke.

PMID- 24918381
TI  - Hemicraniectomy for middle-cerebral-artery stroke.

PMID- 24918382
TI  - Hemicraniectomy for middle-cerebral-artery stroke.

PMID- 24918383
TI  - Chemoimmunotherapy for chronic lymphocytic leukemia. Author reply.

PMID- 24918384
TI  - Chemoimmunotherapy for chronic lymphocytic leukemia.

PMID- 24918385
TI  - Surgical safety checklists in Ontario, Canada. Author reply.

PMID- 24918386
TI  - Surgical safety checklists in Ontario, Canada.

PMID- 24918387
TI  - Surgical safety checklists in ontario, Canada.

PMID- 24918388
TI  - Surgical safety checklists in ontario, Canada.

PMID- 24918389
TI  - Surgical safety checklists in ontario, Canada.

PMID- 24918390
TI  - Surgical safety checklists in ontario, Canada.

PMID- 24918394
TI  - Videos in clinical medicine. Insertion of an intraosseous needle in adults.
AB  - Intraosseous needle insertion is used as a temporary measure when intravascular
      access cannot be achieved through peripheral or central venous routes. The
      intraosseous needle may remain in situ for 72 to 96 hours, but it is best removed
      within 6 to 12 hours, as soon as an alternative site of intravascular access has
      been established. The intraosseous route provides fast and reliable vascular
      access in emergency medical situations. The use of the appropriate technique will
      ensure that the procedure is performed as safely and effectively as possible.

PMID- 24918395
TI  - Images in clinical medicine. A blinking knee.

PMID- 24918396
TI  - Interactive Medical case. Off balance.

PMID- 24918397
TI  - Study on the agonists for the human Toll-like receptor-8 by molecular modeling.
AB  - Toll-like receptor-8 agonists could be promising candidates for vaccine
      adjuvants, especially for neonatal vaccines. In this study, we established
      reliable models and explored valuable information which could explain the known
      experimental facts at the molecular level. Firstly, we divided the whole dataset
      into four splits and obtained many dependable models based on the simplified
      molecular input line entry system (SMILES). Secondly, the whole dataset was
      divided into three splits and other reliable comparative molecular field analysis
      (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models
      were established. Thirdly, we validated the prediction ability of these models
      using various validation methods for the test set. Lastly, for a better
      understanding of the binding modes between agonists and Toll-like receptor-8,
      molecular docking was applied to reveal the structural factors that impact the
      activity of agonists towards Toll-like receptor-8. Furthermore, molecular
      dynamics simulation was employed to further validate the docking results. The
      results obtained from molecular modeling support each other, which not only
      provides models to predict the activities of agonists but also leads to a better
      understanding of the essential features that should be considered when designing
      novel agonists with desired activities. 

PMID- 24918398
TI  - Publications in the European Journal of Pediatric Surgery, Issue 1, Volume 24,
      February 2014.

PMID- 24918399
TI  - Changing Authorship Patterns and Publishing Habits in the European Journal of
      Pediatric Surgery: A 10-Year Analysis.
AB  - AIM: The aim of this study is an analysis of the changing authorship patterns and
      publishing habits encountered in papers published in the European Journal of
      Pediatric Surgery (EJPS) over the past 10 years. Furthermore, it seeks to
      anticipate the trends in the years ahead. MATERIALS AND METHODS: We conducted a
      retrospective review of articles published in the EJPS during a 10-year period
      (January 1, 2003-December 31, 2012). Each article was classified as an Original
      Report/Original Article (OR/OA) or as a Case Report/Case Gallery (CR/CG), and
      they were analyzed separately. For investigation of the percentage distribution
      of publications according to the number of authors per articles, papers were
      combined and into three groups (1-2, 3-5, and 6 <= authors). The analysis focused
      on whether the work was done by members of one institution, or in collaboration
      with other units of the same institution, or in collaboration with other national
      or multinational institutes. RESULTS: In the past 10 years, the EJPS published
      996 articles (616 ORs/OAs, 380 CRs/CGs). The one and two authored publications
      (125) have not decreased, the three to five authored articles (552) changed
      minimally, whereas the number of 6 <= authored publications (319) has increased.
      Of 996 publications, 348 were from single institutes and 648 were written in
      collaboration with two or more other institutes. In addition, in this 10-year
      period, the number of multinational articles has increased significantly from 24
      to 59. CONCLUSION: Increase in cooperation within and between institutions is a
      positive trend, aiming with the goal of improving quality of publications.

PMID- 24918400
TI  - Regenerative medicine in urology.
AB  - Regenerative medicine is an emerging field that is focused on the repair,
      replacement or regeneration of tissues and organs. It involves multiple
      disciplines dedicated to delivering different aspects of the regeneration
      process, including cell biology, material sciences and bioengineering. The
      development of tissue engineering strategies incorporating the use of autologous
      stem cells holds particular promise for overcoming insufficiencies from using
      cells from the patient's own diseased tissues and providing solutions for
      treatment of many disorders of the genitourinary tract. Many experimental
      projects have successfully utilized stem cells and several pilot studies in
      humans indicate the potential of stem cell therapy. However, the discipline is
      still young and further knowledge of both materials and stem cell biology is
      required before this promise can be realized through clinical application. This
      review examines the principles related to regenerative medicine and
      bioengineering focusing on the stem cell isolation expansion and clinical
      application. Analysis of current achievements will be reviewed alongside the
      challenges that remain to be addressed in considering the present and future
      perspectives of regenerative medicine applied to urology. 

PMID- 24918401
TI  - Skingineering.
AB  - Large full-thickness skin defects still represent a significant clinical problem
      for burn, plastic, and reconstructive surgeons. In fact, high morbidity and
      mortality in the acute phase, as well as functionally and cosmetically
      devastating scarring represent vexing problems that are far from being solved in
      a satisfactory way. Although a variety of biologic dressings and cultured skin
      substitutes, in particular cultured epithelial autografts, have contributed to
      improve short- and long-term outcomes of patients in the past, the authors
      hypothesize that only the bioengineering of near-natural autologous full
      thickness skin grafts harbors the potential for a dimensional breakthrough. This
      review gives an insight into the development and characteristics of the
      autologous full-thickness skin grafts available for clinical application to date.
      In addition, recent scientific progress toward the bioengineering of
      dermoepidermal skin grafts which comprise a functional vasculature, pigmentation,
      neural elements, and skin appendages is discussed. 

PMID- 24918402
TI  - Esophagus tissue engineering: designing and crafting the components for the
      "hybrid construct" approach.
AB  - Although being a tubular structure, the esophagus is an extremely complex organ
      to engineer. To engineer an organ, its components and their structure and
      function must be well understood. With regards to esophagus, extensive
      investigations have been performed in experimental models to understand the
      nature of the esophageal epithelial cells with regards to their isolation,
      culture, and growth on scaffolds to generate epithelium. Special subpopulations
      of these cells have been identified that possess proliferative capabilities with
      subsequent differentiative capacity to generate epithelium. Studies have also
      been performed to obtain data on the possibilities of utilizing esophageal
      biopsies from esophagus damaged after caustic exposure for tissue engineering
      applications. Subsequently, attention is being paid to the esophageal smooth
      muscle which is an extremely complex structure responsible for the propulsive
      activities. In addition to the muscle complex, proper functioning of the
      esophagus will require understanding of the enteric nervous system (ENS) that
      controls the propulsive activity in a coordinated manner. Investigations have
      been performed to better understand the esophageal ENS and to isolate and
      maintain these cells under tissue culture conditions. Besides the cellular
      elements, studies have also been performed to seed these cells on scaffolds and
      study the constructs with regards to cell attachment and viability under tissue
      culture conditions. Tests have also been performed on native esophageal tissue to
      understand the functioning of this tissue under the effect of pharmacological
      agents and to establish norms to compare engineered esophageal tissue.
      Vascularization, which is a limiting factor in tissue engineering, has been
      approached with the in situ bioreactor concept using the omentum not only to
      provide vascular ingrowth but also to offer a pedicle for the engineered
      esophagus to enable its surgical transposition. This review offers an insight
      into the advances in esophagus tissue engineering in a large experimental model
      using the "hybrid construct" approach which advocates the precise engineering of
      the tubular gastrointestinal organs based on growth of specific cells on
      specially designed scaffolds and amalgamating them to create the desired complex
      tissue structure. 

PMID- 24918403
TI  - LigaSure Hemorrhoidectomy for Symptomatic Hemorrhoids: First Pediatric
      Experience.
AB  - Hemorrhoids are uncommon in children. Third and fourth degree symptomatic
      hemorrhoids may be surgically excised. We describe the first experience of using
      LigaSure (Covidien, Mansfield, Massachusetts, United States) to perform
      hemorrhoidectomies in children. LigaSure hemorrhoidectomy has been well described
      in adults and is found to be superior in patient tolerance as compared with
      conventional hemorrhoidectomy. 

PMID- 24918404
TI  - Prevalence of overweight and associated factors in under-five-year-old children
      in urban population in Brazil.
AB  - OBJECTIVES: To estimate the prevalence of overweight in children under five years
      old from urban households and to investigate associated factors. METHODS: Cross
      sectional population-based study carried out in the five regions of Brazil with a
      sample of 6,397 children. The World Health Organization 2006 Growth Curves were
      used and children were considered overweight when Z-score was higher than two
      standard deviations of weight for height. The following variables were
      investigated: family income, mothers' education level, race, age, gender, number
      of siblings, weight at birth and duration of exclusive breastfeeding. Proportions
      were compared with the chi2 test and reasons of prevalence were calculated.
      Logistic regression was used for the adjusted analysis. RESULTS: The prevalence
      of overweight was of 12%. After adjustments, this prevalence was significantly
      higher among males (p = 0.030) and inversely proportional to the child's age (p =
      0.032). White children presented 22% higher overweight prevalence than non-white
      ones. A linear direct association was verified between weight at birth and
      overweight (p = 0.000). Children who were breastfed until 120 days presented 34%
      more prevalence of overweight when compared to the ones who were breastfed for a
      longer time. CONCLUSIONS: Overweight prevalence was higher in male, under one
      year old, white children, with more than 3,500 grams of weight at birth and who
      were exclusively breastfed until 120 days.

PMID- 24918405
TI  - Prevalence and sociodemographic characteristics of women with induced abortion in
      a population sample of Sao Paulo, Brazil.
AB  - OBJECTIVES: This study aims at estimating the prevalence of women with induced
      abortion among women of childbearing age (15-49 years) who had any previous
      pregnancy, in the city of Sao Paulo, Brazil, in the last quarter of 2008, and
      identifying the Sociodemographic Characteristics (SC) associated with it.
      METHODS: A cross-sectional survey was carried out. The dependent variable was
      dichotomized as: no abortion and induced abortion. The independent variables
      were: age, paid work/activity, familial monthly income, schooling, marital
      status, contraceptive use and number of live births. Statistical analysis was
      performed using log-binomial regression models with approximation of Poisson to
      estimate the Prevalance Ratios (PR). RESULTS: Of all women with any previous
      pregnancy (n = 683), 4.5% (n = 31) reported induced abortion. The final
      multivariate model showed that having now between 40 and 44 years (PR = 2.76, p =
      0.0043), being single (PR = 2.79, p = 0.0159), having 5 or more live births (PR =
      3.97, p = 0.0013), current oral contraception or IUD use (PR = 2.70, p = 0.454)
      and using a "non effective" (or of low efficacy) contraceptive method (PR = 4.18,
      p = 0.0009) were sociodemographic characteristics associated with induced
      abortion in this population. CONCLUSIONS: Induced abortion seems to be used to
      limit fertility, more precisely after having reached the desired number of
      children. The inadequate use or non-use of effective contraceptive methods, and /
      or the use of contraceptives " non effective", exposed also the women to the risk
      of unintended pregnancies and, therefore, induced abortions. In addition, when
      faced with a pregnancy, single women were more likely to have an abortion than
      married women.

PMID- 24918406
TI  - Agreement on underlying causes of infant death between original records and after
      investigation: analysis of two biennia in the years 2000.
AB  - OBJECTIVE: To analyze the agreement between underlying causes of infant deaths
      obtained from Death Certificates (DC) with those defined after investigation by
      the Municipal Committee for the Prevention of Maternal and Infant Mortality
      (CMPMMI), in Londrina, Parana State, in the biennia 2000-2001 and 2007-2008.
      METHODS: DC of infants and records of investigations were obtained from the
      CMPMMI. The causes of death registered in both sources were coded according to
      the International Classification of Diseases, tenth revision (ICD-10), and the
      underlying causes of deaths were selected. Agreement between underlying causes of
      deaths was verified by Kappa's (k) test and analyzed according to ICD-10 chapters
      and blocks of categories in both biennia. RESULTS: In 2000/2001, according to ICD
      10 chapters, high agreement rates were observed for conditions originated in the
      perinatal period (k = 0.85) and for external causes (k = 0.84), while, for
      congenital malformations, there was a substantial agreement (k = 0.71). In
      2007/2008, agreement was considered poor for all analyzed chapters. For blocks of
      categories, high or substantial agreement rates were observed only in the first
      biennium for "congenital malformations of the circulatory system" (k = 0.78) and
      for "other external causes of accidental injury" (k = 0.91). CONCLUSIONS: A
      decrease in agreement between the sources during the study period indicates
      either an improvement in the process of investigation of infant death by the
      CMPMMI and/or a worsening in the quality of the DC information.

PMID- 24918407
TI  - Sex-specific differences in prevalence and in the factors associated to the
      search for health services in a population based epidemiological study.
AB  - OBJECTIVES: To identify the access to health care services and associated factors
      in adults living in the city of Ribeirao Preto, Sao Paulo, Brazil, in 2007.
      METHODS: A cross-sectional population-based epidemiological study with a sample
      developed in three stages. The variability introduced in the third sampling
      fraction was corrected by the attribution of weights, resulting in a sample of
      2,471 participants. The outcome prevalence was estimated according to socio
      demographic, behavioral and health-related variables. In order to identify
      associated factors, the regression of Poisson was used, obtaining crude and
      adjusted prevalence ratios. All estimates were calculated taking into account the
      effect of the sampling design. RESULTS: The outcome prevalence increased
      according to the age, being higher in female individuals. A different set of
      variables remained in the final models, considering each gender separately. Among
      men, the monthly income > R$ 1,400.00; scores > 823.6 to the Economic Indicator
      of Ribeirao Preto (IERP) and daily average of sitting down time (154.4 - 240
      min/day) constituted themselves into protective factors, whereas the increase of
      age and scholarship, hospitalization, diabetes and hypertension constituted risk
      factors for the use of the services. Among women, health self-reported as
      regular, hospitalization, diabetes and hypertension characterized factors
      positively associated to the outcome at matter. CONCLUSIONS: The results indicate
      the need for planning actions aimed at capturing male individuals, as well as the
      revaluation of detection and control of diabetes and hypertension programs, aimed
      at the primary prevention of terminal cardiovascular events.

PMID- 24918408
TI  - Prevalence of syphilis and associated factors in homeless people of Sao Paulo,
      Brazil, using a Rapid Test.
AB  - INTRODUCTION: Homeless people are a vulnerable group to sexually transmitted
      diseases (STD) with high prevalence of syphilis and hepatitis. OBJECTIVES: To
      estimate the prevalence of syphilis infection and its association with risky
      behaviors for STDs in a sample of homeless people, and to assess the feasibility
      of the use of rapid syphilis test (RST) in this population. METHODS: Cross
      sectional study, in a convenience sample of homeless people assisted in social
      support services of Sao Paulo, between 2006 and 2007. A structured questionnaire
      was applied and RST was performed. In addition, a blood sample for syphilis
      detection was also collected. The sensitivity and specificity of the RST was
      estimated using conventional laboratory diagnosis (VDRL + TPHA) as reference.
      RESULTS: 1,405 volunteers were included in the study. The prevalence rate of
      syphilis was 7.0%, and was associated with homosexual practices (OR(adj) 4.9;
      95%CI 2.6 - 9.4), prior history of STD (OR(adj) 2.6; 95%CI 1.7 - 4.0) and with
      self-referred non-white race (OR(adj) 1.9; 95%CI 1.1 - 3.4). The sensitivity and
      specificity of the RST for syphilis were, respectively, 81.4 and 92.1%.
      CONCLUSION: The high prevalence of syphilis infection among homeless people shows
      the need for actions for its control and the utilization of RST that can be
      considered an efficient strategy due to its sensitivity and specificity. Public
      Health policymakers must strengthen actions for syphilis control, with screening
      tests for syphilis and early treatment, decreasing morbidity with the improvement
      of sexual and reproductive health of the population in general and especially the
      most vulnerable.

PMID- 24918409
TI  - Reliability and validity of a physical activity social support assessment scale
      in adolescents--ASAFA Scale.
AB  - OBJECTIVE: To analyze the reliability and validity of a scale used to measure
      social support for physical activity in adolescents - ASAFA Scale. METHODS: This
      study included 2,755 adolescents (57.6% girls, 16.5 +/- 1.2 years of age), from
      Joao Pessoa, Paraiba, Brazil. Initially, the scale was consisted of 12 items (6
      for social support from parents and 6 from friends). The reliability of the scale
      was estimated by Cronbach's alpha coefficient (alpha), by the Composite
      Reliability (CR), and by the model with two factors and factorial invariance by
      Confirmatory Factor Analysis (CFA) adequacy. RESULTS: The CFA results confirmed
      that the social support scale contained two factors (factor 1: social support
      from parents; factor 2: social support from friends) with five items each (one
      item was excluded from each scale), all with high factor loadings (> 0.65) and
      acceptable adjustment indexes (RMR = 0.050; RMSEA = 0.063; 90%CI: 0.060 - 0.067);
      AGFI = 0.903; GFI = 0.940; CFI = 0.934, NNFI = 0.932). The internal consistency
      was satisfactory (parents: alpha >= 0.77 and CR >= 0.83; friends: alpha >= 0.87
      and CR >= 0.91). The scale's factorial invariance was confirmed (p > 0.05;
      Deltachi2 and DeltaCFI <= 0.01) across all subgroups analyzed (gender, age,
      economic class). The construct validity was evidenced by the significant
      association (p < 0.05) between the adolescents physical activity level and the
      social support score of parents (rho = 0.29) and friends (rho = 0.39).
      CONCLUSIONS: The scale showed reliability, factorial invariance and satisfactory
      validity, so it can be used in studies with adolescents.

PMID- 24918410
TI  - Frequency of consumption of fruits, vegetables and soft drinks: a comparative
      study among adolescents in urban and rural areas.
AB  - OBJECTIVE: To compare the frequency of consumption of fruits, vegetables and soft
      drinks among adolescents living in urban and rural areas of Pernambuco State.
      METHODS: A cross-sectional study based on secondary analysis of data from a
      representative sample of high school students in Pernambuco (n = 4,207, 14 - 19
      years) was conducted. Data were collected through a previously validated
      questionnaire. Adolescents who reported a daily consumption of soft drinks and
      occasional consumption of fruits, juices and vegetables were classified as
      exposed to inadequate standard of consumption of these foods. The independent
      variable was the place of residence (urban/rural). Data were analyzed by
      frequency distribution, chi2 test and binary logistic regression. RESULTS: It was
      observed that students residing in rural areas had a higher prevalence of
      occasional consumption of natural fruit juices (37.6%; 95%CI 36.1 - 39.0) than
      those living in urban areas (32.1%; 95%CI 30.7 - 33.6). The proportion of
      students exposed to daily consumption of soft drinks was higher among those who
      reported they lived in urban areas (65.0%; 95%CI 63.5 - 66.4) compared to those
      who reported living in rural areas (55.3%; 95%CI 53.8 - 56.9). CONCLUSION:
      Adolescent students living in rural areas had a higher prevalence of low
      consumption of natural fruit juices while those residing in urban areas had a
      higher prevalence of daily consumption of soda drinks.

PMID- 24918411
TI  - Characteristics and current direct costs of hospital admissions due to
      occupational accidents in the southwest of Bahia from 2005 to 2007.
AB  - OBJECTIVE: This study aimed to identify the profile and cost of admissions for
      occupational accidents, under the Unified Health System (UHS) in municipalities
      of the southwest of Bahia, in the period of 2005 to 2007. METHODS: It was
      conducted a descriptive study using the records of the Hospital Information
      System (HIS), from which were extracted data about the sociodemographic,
      occupational and hospitalization profiles. To express the results, indicators
      were used as absolute frequencies and proportions, the average stay, Total Cost
      of Hospitalization (TCH), Hospital Mortality (HM), Average Spenditure (AS) and
      Cost per Day (CD). RESULTS: 962 admissions were recorded, of which 94.1% were
      related to path accidents. Among the admitted subjects 65.7% were male, and the
      most affected age groups were 5 to 14 and 15 to 24 years. There were forearm
      fractures on 26 cases of typical accidents. 248 cases of intracranial injuries
      happened during commuting to work, which accounted for 78.2% of traffic accidents
      and 28.8% of falls. The average stay was of 2.6 days and the deaths occurred in
      0.5% of patients discharges. The total cost of the admissions was of R$
      243,125.06, being the AS of R$ 252.73 and CD of R$ 97.44, lower than the external
      causes. The frequencies of the variables related to the occupation were not
      verified due to missing values. CONCLUSION: The data from the HIS Systems were
      limited for identify the profile of the admitted workers. However, they are
      important and can be used on occupational health surveillance.

PMID- 24918412
TI  - Tendencies of mortality by prostate cancer in the states of the Central-West
      Region of Brazil, 1980-2011.
AB  - This study aimed at analyzing the pattern of prostate cancer mortality in the
      Central-West Region, in the period 1980 - 2011. The quadrennial and annual
      mortality rates, age-standardized by the world population, were calculated.
      Polynomial regression models were estimated to analyze trends of mortality in
      Brazilian regions and in the states of the Central-West Region. Throughout Brazil
      there was an increase in the magnitude of mortality rates during the study's
      period. In the Central-West Region, mortality rates from prostate cancer
      increased from 7.65/100,000 in the period 1980 - 1983, to 14.36/100,000 in the
      last four years, exceeding the national average. For Mato Grosso do Sul, an
      increased trend, although not constant, was observed for prostate mortality
      rates, while those rates showed stability for Mato Grosso and presented a
      constant trend of increment for Goias along the studied period. There was a
      statistically significant negative correlation between mortality rates from
      prostate cancer and the proportional mortality from ill-defined causes of death
      in the three states, but no correlations were observed between these rates and
      the ratios of Prostate Specific Antigen (PSA) tests realized. Difficulties in the
      access to the health services network, better quality of death records with
      reduction of ill-defined causes and increased use of PSA may have contributed to
      the mortality pattern observed in the Central-West Region. Further studies are
      needed to investigate these relationships in order, to better understand the
      patterns of mortality from this cancer in the Central-West population. 

PMID- 24918413
TI  - Association between life conditions and vulnerability with mortality from
      cardiovascular diseases in elderly men of Northeast Brazil.
AB  - The study aimed at identifying explanatory factors of the mortality rate of
      elderly men due to cardiovascular diseases in the 187 micro regions of Northeast
      Brazil, in 2000, based on indicators of life conditions and vulnerability of that
      population, using the structural equations modeling. The following methodological
      steps were taken: (1) using Censo 2000's microdata, 10 indicators were selected
      to the latent exogenous construct 'life conditions and vulnerability'. Using the
      Information System of Mortality from the Brazilian Ministry of Health, data about
      deaths from the four major basic causes of cardiovascular diseases were
      collected, which composed the endogenous latent construct as the outcome
      variable; (2) qualitative analysis of mortality data; (3) statistical analysis
      using the structural equation modeling through two phases: adjustment of the
      outcome variables measurement model and adjustment of the obtained structural
      model. Due to the multicollinearity observed, three indicators showed
      significance for the measurement model: years of study, percentage of elderly men
      in households with bathroom/plumbing and survival probability at 60 years of age.
      The structural model indicated adjustment adequacy of the model, which the
      measurement of standardized coefficient was considered of strong effect (SC =
      0.81, p-value < 0.01) and coefficient of determination r2 = 66%. It was concluded
      that indicators of life conditions and vulnerability were highly associated with
      the mortality rate from cardiovascular diseases in elderly men from Northeast
      Brazil in 2000. 

PMID- 24918414
TI  - Prevalence of obesity, overweight and abdominal obesity and its association with
      physical activity in a federal university.
AB  - A cross sectional study to investigate the prevalence of obesity, overweight and
      abdominal obesity and its association with the level of physical activity (PA)
      measured in employees of a Rio de Janeiro University according to the
      International Physical Activity Questionnaire (IPAQ).299 employees selected by
      random sampling were interviewed. The association between PA and anthropometric
      markers was estimated by Poisson models (robust variance). The prevalence of
      obesity was 27.4% (men 22.8% and 36.3% women), the prevalence of overweight was
      63.5% (men 65.0% and women 65.8%) and the prevalence of abdominal obesity was
      45.2% (men 35.5% and 63.7% women). Women reported a higher prevalence of low PA
      (42.2%) compared to men (33.0%). The models adjusted for socio-demographic and
      behavioral variables and habits related to health, showed a significant
      association between PA and the outcomes analyzed. The low level of practice of PA
      (high level reference) has remained associated with the occurrence of obesity (PR
      = 1.89; 95%CI 1.05 - 3.42) and overweight (PR = 1.40; 95%CI 1.08 - 1.80). For the
      abdominal obesity, both the mid level (PR = 1.70; 95%CI 1.11 - 2.58) and the low
      level (PR = 1.74; 95%CI 1.14 - 2.66) were related. This study found inverse
      association between the practice of PA and obesity in line with what has been
      recommended by the WHO, and it reinforces the use of IPAQ in population studies.
      Specifically in relation to abdominal obesity, a remarkable gradient was not
      observed between levels of PA, suggesting that what is important is the high
      level of practice of PA. 

PMID- 24918415
TI  - The International Classification of Functioning, Disability and Health: a
      systematic review of observational studies.
AB  - OBJECTIVE: To systematically review the use of the International Classification
      of Functioning, Disability and Health (ICF) in observational studies. METHODS:
      This study is a systematic review of articles that use the ICF in observational
      studies. We took into account the observational design papers available in
      databases such as PubMed, Lilacs and SciELO, published in English and Portuguese
      from January 2001 to June 2011. We excluded those in which the samples did not
      comprise individuals, those about children and adolescents, and qualitative
      methodology articles. After reading the abstracts of 265 identified articles, 65
      met the inclusion criteria. Of these, 18 were excluded. The STROBE (Strengthening
      the Reporting of Observational Studies in Epidemiology) adapted Checklist, with
      15 items needed for observational studies, was applied to the 47 remaining
      articles. Any paper that met 12 of these criteria was included in this systematic
      review. RESULTS: 29 articles were reviewed. Regarding the ICF application
      methodology, the checklist was used in 31% of the articles, the core set in 31%
      and the ICF categories in 31%. In the remaining 7%, it was not possible to define
      the applied methodology. In most papers (41%), qualifiers were used in their
      original format. As far as the area of knowledge is concerned, most of the
      studies were related to Rheumatology (24%) and Orthopedics (21%). Regarding the
      study design, 83% of the articles used cross-sectional studies. CONCLUSION:
      Results indicate a wide scientific production related to ICF over the past 10
      years. Different areas of knowledge are involved in the debate on the improvement
      of information on morbidity. However, there are only a few quantitative
      epidemiological studies involving the use of ICF. Future studies are needed to
      improve data related to functioning and disability.

PMID- 24918416
TI  - Quality of life of individuals with stroke and their caregivers in a city of
      Triangulo Mineiro.
AB  - OBJECTIVE: To compare the quality of life (QoL) of individuals with stroke and
      their caregivers. METHODS: This is an observational cross-sectional survey,
      involving 83 individuals who suffered a stroke. The participants were divided
      into four groups: group of individuals with stroke who have caregivers (44),
      group of individuals with stroke without caregivers (39), group of caregivers
      (44) and a reference group (83) in the period of March to May 2010. To assess
      QoL, the instrument used was the WHOQOL-bref. RESULTS: The highest scores for the
      four fields were observed increasingly for the group of individuals with stroke
      with caregivers, the stroke group without caregivers followed by the group of
      caregivers and the reference group. The comparison of scores between groups
      showed that the presence of stroke and the fact of being caregiver affect QoL in
      all domains of WHOQOL-bref. CONCLUSION: It was possible to understand the
      negative impact that stroke causes in the lives of the affected ones and their
      caregivers, in order to better target public health policies.

PMID- 24918417
TI  - Aggregation of the four main risk factors to non-communicable diseases among
      adolescents.
AB  - OBJECTIVE: It was to investigate the cluster of four main risk behaviors
      (smoking, alcohol, physical inactivity and low consumption of fruits and
      vegetables) related to chronic diseases from Northeastern Brazil. METHODS: Cross
      sectional study with a representative sample (n = 600) of high school students
      from public schools in Caruaru, Pernambuco, Brazil. The cluster was evaluated by
      comparing the observed prevalence expected in all the possibilities of coupling
      between the behaviors. The logistic regression analysis was performed by grouping
      three or four behaviors, after adjusting for independent variables. RESULTS: With
      the exception of smoking, other risk behaviors had prevalence rates above 20%.
      Only 0.3% (95%CI 0.1 - 1.3) of the students presented the four risk behaviors
      simultaneously, while 15.3% (95%CI 12.3 - 18.2) did not present anyone. Risk
      behaviors tended to cluster, particularly smoking and alcohol consumption, being
      more pronounced among boys, and physical inactivity and low consumption of fruits
      and vegetables among girls (p < 0.05). Regression analysis indicated that, among
      the independent variables, those students who do not have physical education
      classes were 2.1 times more likely to have three or more risk behaviors added.
      CONCLUSIONS: The results of this study allow us to establish the prevalence of
      risk behaviors in cluster, which may have important implications for health
      policies and practices. It is suggested that educational and health actions are
      tested in schools, and physical education classes can be an important context for
      intervention.

PMID- 24918419
TI  - Application of the WHOQOL-BREF in a community segment as a subsidy for health
      promotion actions.
AB  - INTRODUCTION: This article presents the results of a research whose objective was
      to verify the prevalence of the perception reports regarding quality of life of
      library attendees in the public libraries in the Brazilian capital Federal
      District (FD) and the surrounding region and to analyse the factors related to
      dissatisfaction. METHODS: An epidemiological transversal study was conducted in
      592 individuals aged above 12 years old through the application of the WHOQOL
      BREF/WHO questionnaire. RESULTS: Higher frequencies of dissatisfaction were
      observed among women with ages above 25, with lower personal income and lower
      educational level. Dissatisfaction regarding the physical domain was more
      prevalent in the surrounding region than in the FD. Under the psychological
      domain, dissatisfaction predominated in people in the FD. Negative feelings,
      concentration difficulties and dissatisfaction regarding personal safety were
      referred by more than 25% of participants in both regions. Regarding the
      environment domain, lack of money and of leisure opportunities were the main
      complaints. In spite of these findings, interviewees referred being very
      satisfied with their health and quality of life. CONCLUSIONS: The results can be
      a sign that the quality of life in the study region is in alert level. A careful
      look at these data is needed to identify alternatives to change this situation,
      with effective actions for Health Promotion and development strategies for the
      study area. A planning and an intervention in the area of health education in
      public libraries is recommended, since these are very important social loci, that
      can be engaged in health promotion and disease prevention actions in the
      communities.

PMID- 24918418
TI  - Development of a food frequency questionnaire for children from 7 to 10 years
      old.
AB  - OBJECTIVE: To present and discuss the process of the development of a
      Quantitative Food Frequency Questionnaire (QFFQ) aimed to 7-10 year-old children.
      METHODS: A methodological study was performed based on the application of a Food
      Diary (FD) fulfilled by 85 children. Based on registered foods, the diet
      composition in relation to energy and macronutrients was calculated. Foods were
      grouped into items and the percentage of the contribution of each item to the
      diet in terms of calories and macronutrients were calculated. RESULTS: The QFFQ
      was constructed with 92 food items, 76 were selected by Block's method and 16
      were identified from other instruments from literature developed for children and
      adolescents. The food items were grouped in 17 food groups with 3 serving sizes
      and 7 categories to measure food frequency. CONCLUSION: Among the food items, the
      rice was the one that showed the biggest percentage of contribution for energy
      and carbohydrates. For other nutrients, the meat and the milk were the ones that
      contributed most to the consumption of proteins and lipids, respectively.

PMID- 24918420
TI  - Performance of references based on body mass index for detecting excess body
      fatness in schoolchildren aged 7 to 10 years.
AB  - OBJECTIVE: To compare the sensitivity and specificity of body mass index (BMI)
      based classification systems and to determine the optimal cut-offs for predicting
      excess body fatness in schoolchildren. METHODS: 2795 schoolchildren aged 7 - 10
      years were examined. Excess body fatness was defined as the standardized
      residuals of the sum of three skinfold thickness ranking at or above the 90th
      percentile. The international BMI-based system recommended by the World Health
      Organization (WHO-2007) was evaluated on the basis of its sensitivity and
      specificity for detecting excess body fatness and compared with a national BMI
      reference (Brazil-2006). Likelihood ratios analysis was used to select the
      optimal cut-offs in each curve. RESULTS: The two classification systems presented
      high sensitivity (92.5 - 98.6%) and moderate specificity (75.9 - 85.0%) for both
      sexes. The optimal BMI cut-offs improved specificity with no marked loss of
      sensitivity. Using the proposed BMI cut-offs, the post-test probability of
      predicting excess body fatness for children classified as non-overweight
      decreased from 10 (pre-test probability) to 1.4% in girls and to 1.1% in boys.
      For overweight children, this probability increased to more than 46.0%.
      CONCLUSION: The results showed that both the WHO-2007 and Brazil-2006
      classification systems can be used as screening instruments for excess body
      fatness, and that one of the limitations of using the BMI-for-age references
      could be improved by refining the existing cut-offs.

PMID- 24918421
TI  - Assessment of control and epidemiologic details of the schistosomiasis mansoni in
      Bananal, Sao Paulo, Brazil.
AB  - The purpose of our study in the municipality of Bananal, state of Sao Paulo,
      Brazil, was to stop the transmission of schistosomiasis mansoni. Particular
      emphasis was given to such items as the active surveillance and eventual
      treatment of hosts, mapping parasite foci, and increasing the extent of basic
      sanitation in the municipality. Now, our records indicate that the eradication of
      schistosomiasis in the municipality of Bananal is attainable. However, as the
      vector Biomphalaria tenagophila can still be found in some water bodies within
      this municipality, it remains included in the area where schistosomiasis is
      endemic, which calls for very strict measures to avoid the human cases of
      schistososomiasis. The expansion of the coverage of the basic sanitation network
      and treatment of Schistosoma mansoni cases diagnosed during periodic surveys are
      part of the plans to eradicate schistosomiasis in Bananal. 

PMID- 24918422
TI  - A study on the prevalence of adequacy of iron and vitamin C in children's diets.
AB  - The aim of this study was to apply methodological procedures to determine the
      prevalence of adequacy of Iron and vitamin C in children's diets. It was included
      238 children aged 2 to 3 years enrolled in 2009 in 25 day care centers in the
      municipality of Rio de Janeiro. Dietary intake was assessed by weighing the food
      and food record. Assessing the prevalence of nutrient adequacy took into
      consideration the individual and the group. The best estimate of the needs of the
      individual is given by the estimated average requirement (EAR), since we do not
      know the true needs of the individual who is being evaluated. To estimate the
      need of the group method was used EAR as the cutoff. The prevalence of adequacy
      of iron and vitamin C in children's diets was 91.2 and 62.2%, respectively. All
      necessary to achieve the method EAR as the cutoff were used, but became unviable
      the adjustment of the observed consumption data to estimate the distribution of
      usual intake in this group. We conclude that the study of probability of adequacy
      of habitual diet in iron and vitamin C in the age group in question was only
      possible with the use of procedures for the individual. 

PMID- 24918423
TI  - Evaluation of the family health strategy implementation in Santa Catarina in 2004
      and 2008.
AB  - This study aimed to evaluate the implementation of the Family Health Program in
      municipalities of the State of Santa Catarina, Brazil at two different periods
      (2004 and 2008). Two hundred forty-four (83%) municipalities with complete health
      information data comprised the sample. Indicators of coverage, evidence of change
      in the healthcare model, and impact were calculated based on health system
      database. Official documents and observed distribution of measures at the country
      level were used in order to classify municipalities within each indicator. A high
      coverage level increased from 73 to 83% of the cities between 2004 and 2008. Most
      of them showed poor evidence of change in the healthcare model at both time
      points. Increased proportion of cities showed low levels of morbidity by diseases
      sensible to the primary health care from 2004 to 2008. Despite the fact that was
      improvement in coverage and impact indicators over four years, most of the cities
      studied showed poor evidence of change in the healthcare model, warning to the
      review of the health care practices and organization by health professionals and
      managers. 

PMID- 24918424
TI  - [Oral health in the EpiFloripa: a prospective study of adult health in southern
      Brazil].
AB  - OBJECTIVE: To describe methods and challenges of oral health studies nested in a
      prospective cohort study of adults. METHODS: A sample of 2,016 adults was
      investigated in 2009. Household visits were performed in order to apply a
      questionnaire on socioeconomic, demographic, health related variables, medicine
      consumption, blood donation, domestic violence and a set of questions related to
      women's health. Oral health data included self-reported oral health, number of
      remaining teeth, dental services use, perception of dental treatment needs,
      occurrence, intensity and impact of dental pain on daily life, xerostomia and
      chewing impairment due to poor oral health. In addition, participants' blood
      pressure, weight, height and waist circumference were measured. The second wave
      of the study was carried out in 2012. A questionnaire on socioeconomic factors,
      quality of life, discriminatory experiences, 24-hour dietary recall and oral
      health aspects (the same used in 2009) was applied. In addition, blood pressure,
      weight, and waist circumference were measured and clinical oral health status was
      assessed (dental caries, tooth loss, and periodontal outcomes). RESULTS:
      Participation rate was 85.3% (n = 1,720) in 2009 and, among those, 1,222 (71.1%)
      were followed up in 2012. CONCLUSIONS: The follow-up of this population will
      contribute in the elucidation of the potentially causal associations between oral
      outcomes and general chronic diseases.

PMID- 24918425
TI  - How does a carnivore guild utilise a substantial but unpredictable anthropogenic
      food source? Scavenging on hunter-shot ungulate carcasses by wild dogs/dingoes,
      red foxes and feral cats in south-eastern Australia revealed by camera traps.
AB  - There is much interest in understanding how anthropogenic food resources
      subsidise carnivore populations. Carcasses of hunter-shot ungulates are a
      potentially substantial food source for mammalian carnivores. The sambar deer
      (Rusa unicolor) is a large (>= 150 kg) exotic ungulate that can be hunted
      throughout the year in south-eastern Australia, and hunters are not required to
      remove or bury carcasses. We investigated how wild dogs/dingoes and their hybrids
      (Canis lupus familiaris/dingo), red foxes (Vulpes vulpes) and feral cats (Felis
      catus) utilised sambar deer carcasses during the peak hunting seasons (i.e.
      winter and spring). We placed carcasses at 1-km intervals along each of six
      transects that extended 4-km into forest from farm boundaries. Visits to
      carcasses were monitored using camera traps, and the rate of change in edible
      biomass estimated at ~ 14-day intervals. Wild dogs and foxes fed on 70% and 60%
      of 30 carcasses, respectively, but feral cats seldom (10%) fed on carcasses.
      Spatial and temporal patterns of visits to carcasses were consistent with the
      hypothesis that foxes avoid wild dogs. Wild dog activity peaked at carcasses 2
      and 3 km from farms, a likely legacy of wild dog control, whereas fox activity
      peaked at carcasses 0 and 4 km from farms. Wild dog activity peaked at dawn and
      dusk, whereas nearly all fox activity occurred after dusk and before dawn.
      Neither wild dogs nor foxes remained at carcasses for long periods and the amount
      of feeding activity by either species was a less important predictor of the loss
      of edible biomass than season. Reasons for the low impacts of wild dogs and foxes
      on sambar deer carcass biomass include the spatially and temporally unpredictable
      distribution of carcasses in the landscape, the rapid rate of edible biomass
      decomposition in warm periods, low wild dog densities and the availability of
      alternative food resources.

PMID- 24918426
TI  - Combining morphology and genetics in resolving taxonomy--a systematic revision of
      spined loaches (Genus Cobitis; Cypriniformes, Actinopterygii) in the Adriatic
      watershed.
AB  - Taxonomic investigation of spined loaches from Dalmatia and Herzegovina was
      conducted on specimens from 14 localities. The results of the detailed
      morphological investigations were combined with genetic data (based on one
      mitochondrial and two nuclear genes) in order to resolve the taxonomic status of
      each Cobitis population. Among the investigated features of external morphology,
      the appearance of spots on the caudal fin base turned out to have the greatest
      diagnostic value. Furthermore, the number of branched fin rays enabled the
      discrimination of several species. No morphometric character alone could ensure
      determination of any Cobitis species. Nevertheless, groups of populations that
      are more similar in their body shapes correspond to mitochondrial phylogenetic
      lineages. Based on molecular genetic markers, Dalmatian and Herzegovinian spined
      loaches form independent lineages inside the Adriatic phylogenetic group.
      Mitochondrial DNA phylogenetic reconstruction revealed six monophyletic lineages,
      corresponding to six species distributed in the investigated area. The population
      distributed in Mostarsko blato karstic field in Bosnia and Herzegovina is
      described as a new species based on a unique combination of morphological
      characters: a single triangular Canestrini scale; usually 51/2 branched anal fin
      rays, 61/2 branched dorsal fin rays, 14 branched caudal fin rays; no spots in the
      surface pigmentation layer on the caudal fin base; scales on the body very small.

PMID- 24918428
TI  - Spatial measurement of mobility barriers: improving the environment of community
      dwelling older adults in Taiwan.
AB  - Mobility barriers can impede physical activity, increase the fear of falling, and
      pose a threat to the ability of older adults to live independently. This study
      investigated outdoor mobility barriers within a nonretirement public housing
      community located in Tainan, Taiwan. Site observations and interviews with older
      adult residents determined that parked motor scooters, potted plants, the rubber
      tiles of play areas, and a set of steps were the most important barriers. In
      addition, the space syntax parameters of control value and mean depth were
      effectively able to quantitatively measure improvements in walkability resulting
      from the hypothesized removal of these four barriers. These measures of improved
      walkability can be included in a cost-benefit analysis of spatial improvement
      factors to help policymakers address the mobility and accessibility needs of
      older adults. 

PMID- 24918427
TI  - Targeting IL-1beta and IL-17A driven inflammation during influenza-induced
      exacerbations of chronic lung inflammation.
AB  - For patients with chronic lung diseases, such as chronic obstructive pulmonary
      disease (COPD), exacerbations are life-threatening events causing acute
      respiratory distress that can even lead to hospitalization and death. Although a
      great deal of effort has been put into research of exacerbations and potential
      treatment options, the exact underlying mechanisms are yet to be deciphered and
      no therapy that effectively targets the excessive inflammation is available. In
      this study, we report that interleukin-1beta (IL-1beta) and interleukin-17A (IL
      17A) are key mediators of neutrophilic inflammation in influenza-induced
      exacerbations of chronic lung inflammation. Using a mouse model of disease, our
      data shows a role for IL-1beta in mediating lung dysfunction, and in driving
      neutrophilic inflammation during the whole phase of viral infection. We further
      report a role for IL-17A as a mediator of IL-1beta induced neutrophilia at early
      time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1
      resulted in a significant abrogation of neutrophil recruitment to the airways in
      the initial phase of infection or at the peak of viral replication, respectively.
      Therefore, IL-17A and IL-1beta are potential targets for therapeutic treatment of
      viral exacerbations of chronic lung inflammation. 

PMID- 24918429
TI  - Yolk sac mesenchymal progenitor cells from New World mice (Necromys lasiurus)
      with multipotent differential potential.
AB  - Fetal membranes are abundant, ethically acceptable and readily accessible sources
      of stem cells. In particular, the yolk sac is a source of cell lineages that do
      not express MHCs and are mainly free from immunological incompatibles when
      transferred to a recipient. Although data are available especially for
      hematopoietic stem cells in mice and human, whereas other cell types and species
      are dramatically underrepresented. Here we studied the nature and differentiation
      potential of yolk sac derived mesenchymal stem cells from a New World mouse,
      Necromys lasiurus. Explants from mid-gestation were cultured in DMEM-High glucose
      medium with 10% defined fetal bovine serum. The cells were characterized by
      standard methods including immunophenotyping by fluorescence and flow cytometry,
      growth and differentiation potential and tumorigenicity assays. The first
      adherent cells were observed after 7 days of cell culture and included small,
      elongated fibroblast-like cells (92.13%) and large, round epithelial-like cells
      with centrally located nuclei (6.5%). Only the fibroblast-like cells survived the
      first passages. They were positive to markers for mesenchymal stem cells (Stro-1,
      CD90, CD105, CD73) and pluripotency (Oct3/4, Nanog) as well as precursors of
      hematopoietic stem cells (CD117). In differentiation assays, they were classified
      as a multipotent lineage, because they differentiated into osteogenic,
      adipogenic, and chondrogenic lineages and, finally, they did not develop tumors.
      In conclusion, mesenchymal progenitor cells with multipotent differentiation
      potential and sufficient growth and proliferation abilities were able to be
      obtained from Necromys yolk sacs, therefore, we inferred that these cells may be
      promising for a wide range of applications in regenerative medicine. 

PMID- 24918430
TI  - Reliable multi-label learning via conformal predictor and random forest for
      syndrome differentiation of chronic fatigue in traditional Chinese medicine.
AB  - OBJECTIVE: Chronic Fatigue (CF) still remains unclear about its etiology,
      pathophysiology, nomenclature and diagnostic criteria in the medical community.
      Traditional Chinese medicine (TCM) adopts a unique diagnostic method, namely
      'bian zheng lun zhi' or syndrome differentiation, to diagnose the CF with a set
      of syndrome factors, which can be regarded as the Multi-Label Learning (MLL)
      problem in the machine learning literature. To obtain an effective and reliable
      diagnostic tool, we use Conformal Predictor (CP), Random Forest (RF) and Problem
      Transformation method (PT) for the syndrome differentiation of CF. METHODS AND
      MATERIALS: In this work, using PT method, CP-RF is extended to handle MLL
      problem. CP-RF applies RF to measure the confidence level (p-value) of each label
      being the true label, and then selects multiple labels whose p-values are larger
      than the pre-defined significance level as the region prediction. In this paper,
      we compare the proposed CP-RF with typical CP-NBC(Naive Bayes Classifier), CP
      KNN(K-Nearest Neighbors) and ML-KNN on CF dataset, which consists of 736 cases.
      Specifically, 95 symptoms are used to identify CF, and four syndrome factors are
      employed in the syndrome differentiation, including 'spleen deficiency', 'heart
      deficiency', 'liver stagnation' and 'qi deficiency'. THE RESULTS: CP-RF
      demonstrates an outstanding performance beyond CP-NBC, CP-KNN and ML-KNN under
      the general metrics of subset accuracy, hamming loss, one-error, coverage,
      ranking loss and average precision. Furthermore, the performance of CP-RF remains
      steady at the large scale of confidence levels from 80% to 100%, which indicates
      its robustness to the threshold determination. In addition, the confidence
      evaluation provided by CP is valid and well-calibrated. CONCLUSION: CP-RF not
      only offers outstanding performance but also provides valid confidence evaluation
      for the CF syndrome differentiation. It would be well applicable to TCM
      practitioners and facilitate the utilities of objective, effective and reliable
      computer-based diagnosis tool.

PMID- 24918431
TI  - The functional and palaeoecological implications of tooth morphology and wear for
      the megaherbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian)
      of Alberta, Canada.
AB  - Megaherbivorous dinosaurs were exceptionally diverse on the Late Cretaceous
      island continent of Laramidia, and a growing body of evidence suggests that this
      diversity was facilitated by dietary niche partitioning. We test this hypothesis
      using the fossil megaherbivore assemblage from the Dinosaur Park Formation (upper
      Campanian) of Alberta as a model. Comparative tooth morphology and wear,
      including the first use of quantitative dental microwear analysis in the context
      of Cretaceous palaeosynecology, are used to infer the mechanical properties of
      the foods these dinosaurs consumed. The phylliform teeth of ankylosaurs were
      poorly adapted for habitually processing high-fibre plant matter. Nevertheless,
      ankylosaur diets were likely more varied than traditionally assumed: the
      relatively large, bladed teeth of nodosaurids would have been better adapted to
      processing a tougher, more fibrous diet than the smaller, cusp-like teeth of
      ankylosaurids. Ankylosaur microwear is characterized by a preponderance of pits
      and scratches, akin to modern mixed feeders, but offers no support for
      interspecific dietary differences. The shearing tooth batteries of ceratopsids
      are much better adapted to high-fibre herbivory, attested by their scratch
      dominated microwear signature. There is tentative microwear evidence to suggest
      differences in the feeding habits of centrosaurines and chasmosaurines, but
      statistical support is not significant. The tooth batteries of hadrosaurids were
      capable of both shearing and crushing functions, suggestive of a broad dietary
      range. Their microwear signal overlaps broadly with that of ankylosaurs, and
      suggests possible dietary differences between hadrosaurines and lambeosaurines.
      Tooth wear evidence further indicates that all forms considered here exhibited
      some degree of masticatory propaliny. Our findings reveal that tooth morphology
      and wear exhibit different, but complimentary, dietary signals that combine to
      support the hypothesis of dietary niche partitioning. The inferred mechanical and
      dietary patterns appear constant over the 1.5 Myr timespan of the Dinosaur Park
      Formation megaherbivore chronofauna, despite continual species turnover. 

PMID- 24918432
TI  - Acute colonic pseudo-obstruction caused by mycophenolate mofetil in a kidney
      transplant recipient.
AB  - Mycophenolate mofetil is a component of immunosuppressive regimens in solid-organ
      transplant recipients. Gastrointestinal symptoms such as nausea, abdominal pain,
      and diarrhea without fever are common in patients treated with mycophenolate
      mofetil. We treated a patient who had acute colonic pseudo-obstruction after
      kidney transplant that resolved after discontinuing mycophenolate mofetil. The
      disorder recurred soon after resuming mycophenolate mofetil, which is evidence
      for an association between mycophenolate mofetil and acute colonic pseudo
      obstruction in this patient. 

PMID- 24918434
TI  - Coronin3 regulates gastric cancer invasion and metastasis by interacting with
      Arp2.
AB  - Coronin3 expression is increased in gastric cancer (GC) tissues and can promote
      GC invasion and metastasis. However, the mechanisms underlying Coronin3 function
      in GC remain unclear. In this study, we aimed to explore the interacting
      molecules essential for the tumor-promoting effects of Coronin3 in GC. Using mass
      spectrometric analysis, functional studies, and immunohistochemistry, we found
      that Arp2 interacted with Coronin3, and ectopic expression of Arp2 promoted GC
      cell migration and invasion, while Arp2 knockdown suppressed whole-cell motility
      and attenuated the Coronin3-mediated upregulation of cell migration and invasion.
      In addition, both proteins correlated with the metastatic status of GC patients.
      Furthermore, survival analyses demonstrated that both Coronin3 and Arp2
      correlated with overall GC patient survival, and the combination of Coronin3 and
      Arp2 most accurately predicted GC patient prognosis. Combined, these data
      demonstrate that Coronin3 can regulate GC invasion and metastasis through Arp2,
      and the combination of Coronin3 and Arp2 provides a potential marker for
      predicting GC prognosis. 

PMID- 24918435
TI  - Generating visual flickers for eliciting robust steady-state visual evoked
      potentials at flexible frequencies using monitor refresh rate.
AB  - In the study of steady-state visual evoked potentials (SSVEPs), it remains a
      challenge to present visual flickers at flexible frequencies using monitor
      refresh rate. For example, in an SSVEP-based brain-computer interface (BCI), it
      is difficult to present a large number of visual flickers simultaneously on a
      monitor. This study aims to explore whether or how a newly proposed frequency
      approximation approach changes signal characteristics of SSVEPs. At 10 Hz and 12
      Hz, the SSVEPs elicited using two refresh rates (75 Hz and 120 Hz) were measured
      separately to represent the approximation and constant-period approaches. This
      study compared amplitude, signal-to-noise ratio (SNR), phase, latency, scalp
      distribution, and frequency detection accuracy of SSVEPs elicited using the two
      approaches. To further prove the efficacy of the approximation approach, this
      study implemented an eight-target BCI using frequencies from 8-15 Hz. The SSVEPs
      elicited by the two approaches were found comparable with regard to all
      parameters except amplitude and SNR of SSVEPs at 12 Hz. The BCI obtained an
      averaged information transfer rate (ITR) of 95.0 bits/min across 10 subjects with
      a maximum ITR of 120 bits/min on two subjects, the highest ITR reported in the
      SSVEP-based BCIs. This study clearly showed that the frequency approximation
      approach can elicit robust SSVEPs at flexible frequencies using monitor refresh
      rate and thereby can largely facilitate various SSVEP-related studies in neural
      engineering and visual neuroscience. 

PMID- 24918436
TI  - Uridine affects liver protein glycosylation, insulin signaling, and heme
      biosynthesis.
AB  - Purines and pyrimidines are complementary bases of the genetic code. The roles of
      purines and their derivatives in cellular signal transduction and energy
      metabolism are well-known. In contrast, the roles of pyrimidines and their
      derivatives in cellular function remain poorly understood. In this study, the
      roles of uridine, a pyrimidine nucleoside, in liver metabolism are examined in
      mice. We report that short-term uridine administration in C57BL/6J mice increases
      liver protein glycosylation profiles, reduces phosphorylation level of insulin
      signaling proteins, and activates the HRI-eIF-2alpha-ATF4 heme-deficiency stress
      response pathway. Short-term uridine administration is also associated with
      reduced liver hemin level and reduced ability for insulin-stimulated blood
      glucose removal during an insulin tolerance test. Some of the short-term effects
      of exogenous uridine in C57BL/6J mice are conserved in transgenic UPase1-/- mice
      with long-term elevation of endogenous uridine level. UPase1-/- mice exhibit
      activation of the liver HRI-eIF-2alpha-ATF4 heme-deficiency stress response
      pathway. UPase1-/- mice also exhibit impaired ability for insulin-stimulated
      blood glucose removal. However, other short-term effects of exogenous uridine in
      C57BL/6J mice are not conserved in UPase1-/- mice. UPase1-/- mice exhibit normal
      phosphorylation level of liver insulin signaling proteins and increased liver
      hemin concentration compared to untreated control C57BL/6J mice. Contrasting
      short-term and long-term consequences of uridine on liver metabolism suggest that
      uridine exerts transient effects and elicits adaptive responses. Taken together,
      our data support potential roles of pyrimidines and their derivatives in the
      regulation of liver metabolism. 

PMID- 24918437
TI  - Pharmacological analysis of intrinsic neuronal oscillations in rd10 retina.
AB  - In the widely used mouse model of retinal degeneration, rd1, the loss of
      photoreceptors leads to rhythmic electrical activity of around 10-16 Hz in the
      remaining retinal network. Recent studies suggest that this oscillation is formed
      within the electrically coupled network of AII amacrine cells and ON-bipolar
      cells. A second mouse model, rd10, displays a delayed onset and slower
      progression of degeneration, making this mouse strain a better model for human
      retinitis pigmentosa. In rd10, oscillations occur at a frequency of 3-7 Hz,
      raising the question whether oscillations have the same origin in the two mouse
      models. As rd10 is increasingly being used as a model to develop experimental
      therapies, it is important to understand the mechanisms underlying the
      spontaneous rhythmic activity. To study the properties of oscillations in rd10
      retina we combined multi electrode recordings with pharmacological manipulation
      of the retinal network. Oscillations were abolished by blockers for ionotropic
      glutamate receptors and gap junctions. Frequency and amplitude of oscillations
      were modulated strongly by blockers of inhibitory receptors and to a lesser
      extent by blockers of HCN channels. In summary, although we found certain
      differences in the pharmacological modulation of rhythmic activity in rd10
      compared to rd1, the overall pattern looked similar. This suggests that the
      generation of rhythmic activity may underlie similar mechanisms in rd1 and rd10
      retina. 

PMID- 24918440
TI  - Establishment of a simple and rapid identification method for Listeria spp. by
      using high-resolution melting analysis, and its application in food industry.
AB  - Listeria monocytogenes is the causative bacteria of listeriosis, which has a
      higher mortality rate than that of other causes of food poisoning. Listeria spp.,
      of which L. monocytogenes is a member, have been isolated from food and
      manufacturing environments. Several methods have been published for identifying
      Listeria spp.; however, many of the methods cannot identify newly categorized
      Listeria spp. Additionally, they are often not suitable for the food industry,
      owing to their complexity, cost, or time consumption. Recently, high-resolution
      melting analysis (HRMA), which exploits DNA-sequence differences, has received
      attention as a simple and quick genomic typing method. In the present study, a
      new method for the simple, rapid, and low-cost identification of Listeria spp.
      has been presented using the genes rarA and ldh as targets for HRMA. DNA
      sequences of 9 Listeria species were first compared, and polymorphisms were
      identified for each species for primer design. Species specificity of each HRM
      curve pattern was estimated using type strains of all the species. Among the 9
      species, 7 were identified by HRMA using rarA gene, including 3 new species. The
      remaining 2 species were identified by HRMA of ldh gene. The newly developed HRMA
      method was then used to assess Listeria isolates from the food industry, and the
      method efficiency was compared to that of identification by 16S rDNA sequence
      analysis. The 2 methods were in coherence for 92.6% of the samples, demonstrating
      the high accuracy of HRMA. The time required for identifying Listeria spp. was
      substantially low, and the process was considerably simplified, providing a
      useful and precise method for processing multiple samples per day. Our newly
      developed method for identifying Listeria spp. is highly valuable; its use is not
      limited to the food industry, and it can be used for the isolates from the
      natural environment. 

PMID- 24918438
TI  - Enzymatic sialylation of IgA1 O-glycans: implications for studies of IgA
      nephropathy.
AB  - Patients with IgA nephropathy (IgAN) have elevated circulating levels of IgA1
      with some O-glycans consisting of galactose (Gal)-deficient N-acetylgalactosamine
      (GalNAc) with or without N-acetylneuraminic acid (NeuAc). We have analyzed O
      glycosylation heterogeneity of naturally asialo-IgA1 (Ale) myeloma protein that
      mimics Gal-deficient IgA1 (Gd-IgA1) of patients with IgAN, except that IgA1 O
      glycans of IgAN patients are frequently sialylated. Specifically, serum IgA1 of
      healthy controls has more alpha2,3-sialylated O-glycans (NeuAc attached to Gal)
      than alpha2,6-sialylated O-glycans (NeuAc attached to GalNAc). As IgA1-producing
      cells from IgAN patients have an increased activity of alpha2,6-sialyltransferase
      (ST6GalNAc), we hypothesize that such activity may promote premature sialylation
      of GalNAc and, thus, production of Gd-IgA1, as sialylation of GalNAc prevents
      subsequent Gal attachment. Distribution of NeuAc in IgA1 O-glycans may play an
      important role in the pathogenesis of IgAN. To better understand biological
      functions of NeuAc in IgA1, we established protocols for enzymatic sialylation
      leading to alpha2,3- or alpha2,6-sialylation of IgA1 O-glycans. Sialylation of
      Gal-deficient asialo-IgA1 (Ale) myeloma protein by an ST6GalNAc enzyme generated
      sialylated IgA1 that mimics the Gal-deficient IgA1 glycoforms in patients with
      IgAN, characterized by alpha2,6-sialylated Gal-deficient GalNAc. In contrast,
      sialylation of the same myeloma protein by an alpha2,3-sialyltransferase yielded
      IgA1 typical for healthy controls, characterized by alpha2,3-sialylated Gal. The
      GalNAc-specific lectin from Helix aspersa (HAA) is used to measure levels of Gd
      IgA1. We assessed HAA binding to IgA1 sialylated at Gal or GalNAc. As expected,
      alpha2,6-sialylation of IgA1 markedly decreased reactivity with HAA. Notably,
      alpha2,3-sialylation also decreased reactivity with HAA. Neuraminidase treatment
      recovered the original HAA reactivity in both instances. These results suggest
      that binding of a GalNAc-specific lectin is modulated by sialylation of GalNAc as
      well as Gal in the clustered IgA1 O-glycans. Thus, enzymatic sialylation offers a
      useful model to test the role of NeuAc in reactivities of the clustered O-glycans
      with lectins. 

PMID- 24918441
TI  - New insights on developmental dyslexia subtypes: heterogeneity of mixed reading
      profiles.
AB  - We examined whether classifications based on reading performance are relevant to
      identify cognitively homogeneous subgroups of dyslexic children. Each of the 71
      dyslexic participants was selected to have a mixed reading profile, i.e. poor
      irregular word and pseudo-word reading performance (accuracy and speed). Despite
      their homogeneous reading profile, the participants were found to split into four
      distinct cognitive subgroups, characterized by a single phonological disorder, a
      single visual attention span disorder, a double deficit or none of these
      disorders. The two subgroups characterized by single and contrasted cognitive
      disorders were found to exhibit a very similar reading pattern but more
      contrasted spelling performance (quantitative analysis). A qualitative analysis
      of the error types produced in reading and spelling provided some cues about the
      participants' underlying cognitive deficit. The overall findings disqualify
      subtyping based on reading profiles as a classification method to identify
      cognitively homogeneous subgroups of dyslexic children. They rather show an
      opaque relationship between the cognitive underpinnings of developmental dyslexia
      and their behavioral manifestations in reading and spelling. Future neuroimaging
      and genetic studies should take this issue into account since synthesizing over
      cognitively heterogeneous children would entail potential pitfalls. 

PMID- 24918442
TI  - Future declines of coronary heart disease mortality in England and Wales could
      counter the burden of population ageing.
AB  - BACKGROUND: Coronary Heart Disease (CHD) remains a major cause of mortality in
      the United Kingdom. Yet predictions of future CHD mortality are potentially
      problematic due to population ageing and increase in obesity and diabetes. Here
      we explore future projections of CHD mortality in England & Wales under two
      contrasting future trend assumptions. METHODS: In scenario A, we used the
      conventional counterfactual scenario that the last-observed CHD mortality rates
      from 2011 would persist unchanged to 2030. The future number of deaths was
      calculated by applying those rates to the 2012-2030 population estimates. In
      scenario B, we assumed that the recent falling trend in CHD mortality rates would
      continue. Using Lee-Carter and Bayesian Age Period Cohort (BAPC) models, we
      projected the linear trends up to 2030. We validate our methods using past data
      to predict mortality from 2002-2011. Then, we computed the error between observed
      and projected values. RESULTS: In scenario A, assuming that 2011 mortality rates
      stayed constant by 2030, the number of CHD deaths would increase 62% or
      approximately 39,600 additional deaths. In scenario B, assuming recent declines
      continued, the BAPC model (the model with lowest error) suggests the number of
      deaths will decrease by 56%, representing approximately 36,200 fewer deaths by
      2030. CONCLUSIONS: The decline in CHD mortality has been reasonably continuous
      since 1979, and there is little reason to believe it will soon halt. The commonly
      used assumption that mortality will remain constant from 2011 therefore appears
      slightly dubious. By contrast, using the BAPC model and assuming continuing
      mortality falls offers a more plausible prediction of future trends. Thus,
      despite population ageing, the number of CHD deaths might halve again between
      2011 and 2030. This has implications for how the potential benefits of future
      cardiovascular strategies might best be calculated and presented.

PMID- 24918443
TI  - Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed
      chitosan scaffold.
AB  - Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor
      chondrogenic potential. When combined with 3D polymeric structures, the stem
      cells provide a source of stem cells to engineer 3D tissues for cartilage repair.
      In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan
      scaffolds can undergo chondrogenesis using TGFbeta3 and BMP6. By week 4, a
      pearlescent, cartilage-like matrix had formed that penetrated the top layers of
      the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology
      showed typical cells encased in extracellular matrix which stained positively
      with toluidine blue. Immunohistochemistry demonstrated positive staining for
      collagen type II and cartilage proteoglycans, as well as collagen type I. Real
      time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9
      genes when IPFP-ASCs were stimulated by TGFbeta3 and BMP6. Thus, IPFP-ASCs can
      successfully undergo chondrogenesis using TGFbeta3 and BMP6 and the cartilage
      like tissue that forms on the surface of 3D-printed chitosan scaffold may prove
      useful as an osteochondral graft. 

PMID- 24918444
TI  - Molecular detection of bioluminescent dinoflagellates in surface waters of the
      Patagonian shelf during early austral summer 2008.
AB  - We investigated the distribution of bioluminescent dinoflagellates in the
      Patagonian Shelf region using "universal" PCR primers for the dinoflagellate
      luciferase gene. Luciferase gene sequences and single cell PCR tests, in
      conjunction with taxonomic identification by microscopy, allowed us to identify
      and quantify bioluminescent dinoflagellates. We compared these data to
      coincidental discrete optical measurements of stimulable bioluminescence
      intensity. Molecular detection of the luciferase gene showed that bioluminescent
      dinoflagellates were widespread across the majority of the Patagonian Shelf
      region. Their presence was comparatively underestimated by optical
      bioluminescence measurements, whose magnitude was affected by interspecific
      differences in bioluminescence intensity and by the presence of other
      bioluminescent organisms. Molecular and microscopy data showed that the complex
      hydrography of the area played an important role in determining the distribution
      and composition of dinoflagellate populations. Dinoflagellates were absent south
      of the Falkland Islands where the cold, nutrient-rich, and well-mixed waters of
      the Falklands Current favoured diatoms instead. Diverse populations of
      dinoflagellates were present in the warmer, more stratified waters of the
      Patagonian Shelf and Falklands Current as it warmed northwards. Here, the
      dinoflagellate population composition could be related to distinct water masses.
      Our results provide new insight into the prevalence of bioluminescent
      dinoflagellates in Patagonian Shelf waters and demonstrate that a molecular
      approach to the detection of bioluminescent dinoflagellates in natural waters is
      a promising tool for ecological studies of these organisms. 

PMID- 24918445
TI  - Quantification of carbon and phosphorus co-limitation in bacterioplankton: new
      insights on an old topic.
AB  - Because the nature of the main resource that limits bacterioplankton (e.g.
      organic carbon [C] or phosphorus [P]) has biogeochemical implications concerning
      organic C accumulation in freshwater ecosystems, empirical knowledge is needed
      concerning how bacteria respond to these two resources, available alone or
      together. We performed field experiments of resource manipulation (2*2 factorial
      design, with the addition of C, P, or both combined) in two Mediterranean
      freshwater ecosystems with contrasting trophic states (oligotrophy vs. eutrophy)
      and trophic natures (autotrophy vs. heterotrophy, measured as gross primary
      production:respiration ratio). Overall, the two resources synergistically co
      limited bacterioplankton, i.e. the magnitude of the response of bacterial
      production and abundance to the two resources combined was higher than the
      additive response in both ecosystems. However, bacteria also responded positively
      to single P and C additions in the eutrophic ecosystem, but not to single C in
      the oligotrophic one, consistent with the value of the ratio between bacterial C
      demand and algal C supply. Accordingly, the trophic nature rather than the
      trophic state of the ecosystems proves to be a key feature determining the
      expected types of resource co-limitation of bacteria, as summarized in a proposed
      theoretical framework. The actual types of co-limitation shifted over time and
      partially deviated (a lesser degree of synergism) from the theoretical
      expectations, particularly in the eutrophic ecosystem. These deviations may be
      explained by extrinsic ecological forces to physiological limitations of
      bacteria, such as predation, whose role in our experiments is supported by the
      relationship between the dynamics of bacteria and bacterivores tested by SEMs
      (structural equation models). Our study, in line with the increasingly recognized
      role of freshwater ecosystems in the global C cycle, suggests that further
      attention should be focussed on the biotic interactions that modulate resource co
      limitation of bacteria. 

PMID- 24918446
TI  - Dose-dependent effect of estrogen suppresses the osteo-adipogenic
      transdifferentiation of osteoblasts via canonical Wnt signaling pathway.
AB  - Fat infiltration within marrow cavity is one of multitudinous features of
      estrogen deficiency, which leads to a decline in bone formation functionality.
      The origin of this fat is unclear, but one possibility is that it is derived from
      osteoblasts, which transdifferentiate into adipocytes that produce bone marrow
      fat. We examined the dose-dependent effect of 17beta-estradiol on the ability of
      MC3T3-E1 cells and murine bone marrow-derived mesenchymal stem cell (BMMSC)
      derived osteoblasts to undergo osteo-adipogenic transdifferentiation. We found
      that 17beta-estradiol significantly increased alkaline phosphatase activity
      (P<0.05); calcium deposition; and Alp, Col1a1, Runx2, and Ocn expression levels
      dose-dependently. By contrast, 17beta-estradiol significantly decreased the
      number and size of lipid droplets, and Fabp4 and PPARgamma expression levels
      during osteo-adipogenic transdifferentiation (P<0.05). Moreover, the expression
      levels of brown adipocyte markers (Myf5, Elovl3, and Cidea) and undifferentiated
      adipocyte markers (Dlk1, Gata2, and Wnt10b) were also affected by 17beta
      estradiol during osteo-adipogenic transdifferentiation. Western blotting and
      immunostaining further showed that canonical Wnt signaling can be activated by
      estrogen to exert its inhibitory effect of osteo-adipogenesis. This is the first
      study to demonstrate the dose-dependent effect of 17beta-estradiol on the osteo
      adipogenic transdifferentiation of MC3T3-E1 cells and BMMSCs likely via canonical
      Wnt signaling. In summary, our results indicate that osteo-adipogenic
      transdifferentiation modulated by canonical Wnt signaling pathway in bone
      metabolism may be a new explanation for the gradually increased bone marrow fat
      in estrogen-inefficient condition. 

PMID- 24918448
TI  - Predation on rose galls: parasitoids and predators determine gall size through
      directional selection.
AB  - Both predators and parasitoids can have significant effects on species' life
      history traits, such as longevity or clutch size. In the case of gall inducers,
      sporadically there is evidence to suggest that both vertebrate predation and
      insect parasitoid attack may shape the optimal gall size. While the effects of
      parasitoids have been studied in detail, the influence of vertebrate predation is
      less well-investigated. To better understand this aspect of gall size evolution,
      we studied vertebrate predation on galls of Diplolepis rosae on rose (Rosa
      canina) shrubs. We measured predation frequency, predation incidence, and
      predation rate in a large-scale observational field study, as well as an
      experimental field study. Our combined results suggest that, similarly to
      parasitoids, vertebrate predation makes a considerable contribution to mortality
      of gall inducer larvae. On the other hand, its influence on gall size is in
      direct contrast to the effect of parasitoids, as frequency of vertebrate
      predation increases with gall size. This suggests that the balance between
      predation and parasitoid attack shapes the optimal size of D. rosae galls. 

PMID- 24918447
TI  - The effects of vitamin D supplementation on hepatic dysfunction, vitamin D
      status, and glycemic control in children and adolescents with vitamin D
      deficiency and either type 1 or type 2 diabetes mellitus.
AB  - BACKGROUND: The effects of vitamin D supplementation on mild hepatic dysfunction
      and glycemic control are unclear in children and adolescents with either type 1
      (T1D) or type 2 diabetes (T2D). HYPOTHESIS: Vitamin D supplementation will
      improve hepatic dysfunction and glycemic control. AIM: To determine the effect of
      vitamin D supplementation on alanine transaminase (ALT), hemoglobin A1c (HbA1c),
      and serum 25-hydroxyvitamin D [25(OH)D] concentration. SUBJECTS AND METHODS: A
      retrospective study of 131 subjects with either T1D (n = 88 ? 46 females, 42
      males), or T2D (n = 43 ? 26 females, 17 males) of ages 3-18 years between 2007
      2013. All subjects had (1) a diagnosis of diabetes for > 12 mo, (2) received
      vitamin D supplementation for the management of vitamin D deficiency (3) had
      baseline and subsequent simultaneous measurements of HbA1c, ALT, and 25(OH)D.
      Vitamin D deficiency was defined as 25(OH)D concentration of < 50 nmol/L (20
      ng/mL). RESULTS: At baseline, vitamin D deficiency occurred in 72.1% of patients
      with T2D and in 37.5% of T1D patients (p < 0.001). Patients with T2D had
      significantly higher values for BMI SDS (p < 0.001), alanine transaminase (ALT)
      (p = 0.001), but lower 25(OH)D p < 0.001), and no difference in HbA1c (p = 0.94),
      and total daily dose (TDD) of insulin per kg body weight (p = 0.48) as compared
      to T1D patients. After 3 months of vitamin D supplementation, there was a
      significant increase in 25(OH)D in both T2D (p = 0.015), and T1D patients (p <
      0.001); significant reduction in BMI SDS (p = 0.015) and ALT (p = 0.012) in T2D,
      but not in T1D. There was a clinically-significant decrease in HbA1c in T2D from
      8.5 +/- 2.9% at baseline to 7.7 +/- 2.5 at 3 mo, but not in T1D, 8.5 +/- 1.2 to
      8.53 +/- 1.1%. CONCLUSIONS: Vitamin D supplementation in subjects with T2D was
      associated with statistically significant decreases in BMI SDS, ALT, and a
      clinically-significant decrease in HbA1c.

PMID- 24918449
TI  - SHARP1 suppresses angiogenesis of endometrial cancer by decreasing hypoxia
      inducible factor-1alpha level.
AB  - Recent data support a role for SHARP1, a basic helix-loop-helix transcription
      repressor, in the regulation of malignant cell behavior in several human cancers.
      However, the expression and role of SHARP1 during the development of endometrial
      cancer (EC) remain unclear. Here we show that upregulation of SHARP1 suppressed
      tumor angiogenesis by decreasing hypoxia-inducible factor-1alpha (HIF-1alpha),
      inhibited cell viability and tumor growth in EC. Immunohistochemical staining
      showed that the expression of SHARP1 was negatively correlated with tumor stage,
      histological grade, myometrial invasion, lymph node metastasis, blood vessel
      permeation in the myometrium and HIF-1alpha expression. Mechanistic studies
      showed that SHARP1 interacted with HIF-1alpha physically, and the protein level
      of HIF-1alpha and the mRNA level of its target genes (VEGFA, ANGPTL4 and CA9)
      were decreased by SHARP1 under hypoxia. Upregulation of SHARP1 in EC impeded
      hypoxia-induced angiogenesis by reducing VEGF secretion. Immunohistochemical
      analysis verified a correlation between decreased SHARP1 expression and increased
      microvessel density in EC tissues. Additionally, SHARP1 inhibited cell viability
      in EC cell lines. Overexpression of SHARP1 in vivo inhibited tumor growth and
      angiogenesis, and decreased HIF-1alpha expression. In this study, we established
      SHARP1 as a novel tumor suppressor of EC and shed light on the mechanisms by how
      SHARP1 inhibited EC progression. Therefore, SHARP1 may be a valuable prognostic
      biomarker for EC progression and shows promise as a new potential target for
      antiangiogenic therapeutics in human EC. 

PMID- 24918451
TI  - Majority of women are influenced by nonprofessional information sources when
      deciding to consult a complementary and alternative medicine practitioner during
      pregnancy.
AB  - OBJECTIVES: Up to 87% of women are using some form of complementary and
      alternative medicine (CAM) during their pregnancy, and this study was conducted
      to investigate the information sources that these women find influential in
      relation to such use. DESIGN: The study sample was obtained via the Australian
      Longitudinal Study on Women's Health. This article is based on a substudy of 1835
      pregnant women who were surveyed in 2010. The women answered questions about CAM
      use, pregnancy-related health concerns, and influential information sources in
      relation to CAM use. Logistic regression models were used to determine the
      information sources that women reported as influential in their decision making
      regarding CAM use. RESULTS: Of the respondents (n=1835, 79.2% response rate),
      48.1% (n=623) of the pregnant women consulted a CAM practitioner and 91.7%
      (n=1485) used a CAM product during pregnancy. The results show that, of the women
      who used CAM, nearly half (48%, n=493) were influenced by their own personal
      experience of CAM and 43% (n=423) by family and friends. Other popular sources of
      information were general practitioners 27% (n=263), the media (television, radio,
      books, magazines, newspapers) 22% (n=220), obstetricians 21% (n=208) and midwives
      19% (n=190). Numerous statistically significant associations between influential
      information sources and pregnancy-related health conditions were identified.
      CONCLUSIONS: Women utilize a wide variety of information sources regarding their
      CAM use during pregnancy. Nonprofessional sources of information were found to be
      particularly influential, and maternity health care professionals need to have a
      nonjudgmental and open discussion with women about their CAM use during pregnancy
      in order to ensure safe and effective maternal outcomes.

PMID- 24918450
TI  - The human antibody response to the surface of Mycobacterium tuberculosis.
AB  - BACKGROUND: Vaccine-induced human antibodies to surface components of Haemophilus
      influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal
      antibodies to surface components of Mycobacterium tuberculosis are also
      protective in animal models. We have characterized human antibodies that bind to
      the surface of live M. tuberculosis. METHODS: Plasma from humans with latent
      tuberculosis (TB) infection (n = 23), active TB disease (n = 40), and uninfected
      controls (n = 9) were assayed by ELISA for reactivity to the live M. tuberculosis
      surface and to inactivated M. tuberculosis fractions (whole cell lysate,
      lipoarabinomannan, cell wall, and secreted proteins). RESULTS: When compared to
      uninfected controls, patients with active TB disease had higher antibody titers
      to the surface of live M. tuberculosis (Delta = 0.72 log10), whole cell lysate
      (Delta = 0.82 log10), and secreted proteins (Delta = 0.62 log10), though there
      was substantial overlap between the two groups. Individuals with active disease
      had higher relative IgG avidity (Delta = 1.4 to 2.6) to all inactivated
      fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis
      surface was lower in the active disease group than in uninfected controls (Delta
      =  -1.53, p = 0.004). Patients with active disease had higher IgG than IgM titers
      for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers
      to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the
      M. tuberculosis surface were observed in active disease patients who were BCG
      vaccinated (Delta = 0.55 log10, p = 0.008), foreign-born (Delta = 0.61 log10, p =
      0.004), or HIV-seronegative (Delta = 0.60 log10, p = 0.04). Higher relative IgG
      avidity scores to the M. tuberculosis surface were also observed in active
      disease patients who were BCG-vaccinated (Delta = 1.12, p < 0.001) and foreign
      born (Delta = 0.87, p = 0.01). CONCLUSIONS/SIGNIFICANCE: Humans with active TB
      disease produce antibodies to the surface of M. tuberculosis with low avidity and
      with a low IgG/IgM ratio. Highly-avid IgG antibodies to the M. tuberculosis
      surface may be an appropriate target for future TB vaccines.

PMID- 24918452
TI  - Chlorella zofingiensis as an alternative microalgal producer of astaxanthin:
      biology and industrial potential.
AB  - Astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione), a high-value
      ketocarotenoid with a broad range of applications in food, feed, nutraceutical,
      and pharmaceutical industries, has been gaining great attention from science and
      the public in recent years. The green microalgae Haematococcus pluvialis and
      Chlorella zofingiensis represent the most promising producers of natural
      astaxanthin. Although H. pluvialis possesses the highest intracellular
      astaxanthin content and is now believed to be a good producer of astaxanthin, it
      has intrinsic shortcomings such as slow growth rate, low biomass yield, and a
      high light requirement. In contrast, C. zofingiensis grows fast phototrophically,
      heterotrophically and mixtrophically, is easy to be cultured and scaled up both
      indoors and outdoors, and can achieve ultrahigh cell densities. These robust
      biotechnological traits provide C. zofingiensis with high potential to be a
      better organism than H. pluvialis for mass astaxanthin production. This review
      aims to provide an overview of the biology and industrial potential of C.
      zofingiensis as an alternative astaxanthin producer. The path forward for further
      expansion of the astaxanthin production from C. zofingiensis with respect to both
      challenges and opportunities is also discussed. 

PMID- 24918454
TI  - Acetylcholinesterase inhibitory activity of pigment echinochrome A from sea
      urchin Scaphechinus mirabilis.
AB  - Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone
      class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase
      (AChE) inhibitors are used in the treatment of various neuromuscular disorders,
      and are considered as strong therapeutic agents for the treatment of Alzheimer's
      disease (AD). Although EchA is clinically used to treat ophthalmic diseases and
      limit infarct formation during ischemia/ reperfusion injury, anti-AChE effect of
      EchA is still unknown. In this study, we investigated the anti-AChE effect of
      EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did
      not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited
      AChE with an irreversible and uncompetitive mode. In addition, EchA showed
      reactive oxygen species scavenging activity, particularly with nitric oxide.
      These findings indicate new therapeutic potential for EchA in treating reduced
      acetylcholine-related diseases including AD and provide an insight into
      developing new AChE inhibitors. 

PMID- 24918455
TI  - A review of potable water accessibility and sustainability issues in developing
      countries - case study of Uganda.
AB  - Providing sources of sustainable and quality potable water in Uganda is a
      significant public health issue. This project aimed at identifying and
      prioritizing possible actions on how sustainable high quality potable water in
      Uganda's water supply systems could be achieved. In that respect, a review of
      both the current water supply systems and government programs on drinking water
      in Uganda was completed. Aspects of quantity, quality, treatment methods,
      infrastructure, storage and distribution of water for different water systems
      were evaluated and compared with the existing water supply systems in the U.S.,
      Latin America and the Caribbean, for purposes of generating feasible
      recommendations and opportunities for improvement. Uganda utilizes surface water,
      groundwater, and rainwater sources for consumption. Surface water covers 15.4% of
      the land area and serves both urban and rural populations. Lake Victoria
      contributes about 85% of the total fresh surface water. Potable water quality is
      negatively affected by the following factors: disposal of sewage and industrial
      effluents, agricultural pesticides and fertilizers, and surface run-offs during
      heavy rains. The total renewable groundwater resources in Uganda are estimated to
      be 29 million m3/year with about 20,000 boreholes, 3000 shallow-wells and 200,000
      springs, serving more than 80% of the rural and slum communities. Mean annual
      rainfall in Uganda ranges from 500 mm to 2500 mm. Groundwater and rainwater
      quality is mainly affected by poor sanitation and unhygienic practices. There are
      significant regional variations in the accessibility of potable water, with the
      Northeastern region having the least amount of potable water from all sources.
      Uganda still lags behind in potable water resource development. Priorities should
      be placed mainly on measures available for improvement of groundwater and
      rainwater resource utilization, protection of watersheds, health education,
      improved water treatment methods and distribution in rural areas, and pollution
      control and monitoring. Implementing these changes can promote potable water
      accessibility especially to the poor populations living in rural and urban slum
      areas because they comprise the majority (80%) of Uganda's population.

PMID- 24918453
TI  - Emerging strategies and integrated systems microbiology technologies for
      biodiscovery of marine bioactive compounds.
AB  - Marine microorganisms continue to be a source of structurally and biologically
      novel compounds with potential use in the biotechnology industry. The unique
      physiochemical properties of the marine environment (such as pH, pressure,
      temperature, osmolarity) and uncommon functional groups (such as isonitrile,
      dichloroimine, isocyanate, and halogenated functional groups) are frequently
      found in marine metabolites. These facts have resulted in the production of
      bioactive substances with different properties than those found in terrestrial
      habitats. In fact, the marine environment contains a relatively untapped
      reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics,
      combinatorial biosynthesis, synthetic biology, screening methods, expression
      systems, bioinformatics, and the ever increasing availability of sequenced
      genomes provides us with more opportunities than ever in the discovery of novel
      bioactive compounds and biocatalysts. The combination of these advanced
      techniques with traditional techniques, together with the use of dereplication
      strategies to eliminate known compounds, provides a powerful tool in the
      discovery of novel marine bioactive compounds. This review outlines and discusses
      the emerging strategies for the biodiscovery of these bioactive compounds. 

PMID- 24918456
TI  - Multiclass cancer classification based on gene expression comparison.
AB  - As the complexity and heterogeneity of cancer is being increasingly appreciated
      through genomic analyses, microarray-based cancer classification comprising
      multiple discriminatory molecular markers is an emerging trend. Such multiclass
      classification problems pose new methodological and computational challenges for
      developing novel and effective statistical approaches. In this paper, we
      introduce a new approach for classifying multiple disease states associated with
      cancer based on gene expression profiles. Our method focuses on detecting small
      sets of genes in which the relative comparison of their expression values leads
      to class discrimination. For an m-class problem, the classification rule
      typically depends on a small number of m-gene sets, which provide transparent
      decision boundaries and allow for potential biological interpretations. We first
      test our approach on seven common gene expression datasets and compare it with
      popular classification methods including support vector machines and random
      forests. We then consider an extremely large cohort of leukemia cancer patients
      to further assess its effectiveness. In both experiments, our method yields
      comparable or even better results to benchmark classifiers. In addition, we
      demonstrate that our approach can integrate pathway analysis of gene expression
      to provide accurate and biological meaningful classification.

PMID- 24918457
TI  - Event-related potentials show taste and risk effects on food evaluation.
AB  - Tastes and claims about unhealthy food are important factors that affect
      consumption. This study investigated the correlation of the event-related
      potential (ERP) of the evaluation of processing of food information with the task
      of positive judgment. Given the information on possible diseases that arise with
      food consumption, sweet-tasting food elicited more conflict than salty food, and
      this conflict was reflected by a negative ERP component at 250-500 ms (N400).
      Moreover, the late positive wave at 500-800 ms that was evoked by presentation of
      food with the names of chronic diseases that could arise from the consumption of
      such food was larger than that evoked when acute diseases were presented. Sweet
      tasting food caused a more intense conflict with disease-related risk than salty
      food, and chronic diseases aroused a stronger emotional fear than acute diseases.
      These findings provide new insights into the N400 component and the
      neurocognitive processes of evaluating food combined with taste and risk
      information. 

PMID- 24918458
TI  - D609-mediated inhibition of ATP synthesis in neural progenitor cells.
AB  - Tricyclodecan-9-yl-xanthogenate (D609) is an antioxidative molecule with
      antiproliferative and neuroprotective properties in a variety of cells.
      Previously, we have shown that D609 decreased the proliferation of neural
      progenitor cells. In this study, we examined the antioxidative property of D609
      on neural progenitor cells isolated from the subventricular zone of the rat
      brain. Cellular oxidation was assessed by measuring the ATP content of the cells.
      Our results show that D609 decreased the ATP content of the neural progenitor
      cells by ~40%, suggesting the possible inhibition of cellular metabolic activity.
      Cytochrome c oxidase (Cox), also known as complex IV of the electron transport
      chain, is a terminal enzyme involved in the oxidation of substrates resulting in
      the generation of energy required for the cellular activity. Therefore,
      regulating the activity of Cox could interfere with the generation of ATP,
      consequently affecting the proliferation of cells. Consistent with this
      hypothesis, we also observed a decrease in the Cox activity following the
      incubation of neural progenitor cells with D609. These results suggest that D609
      could inhibit the activity of Cox and subsequent ATP synthesis in the neural
      progenitor cells. 

PMID- 24918459
TI  - Involvement of extracellular factors in maintaining self-renewal of neural stem
      cell by nestin.
AB  - Nestin knockout leads to embryonic lethality and self-renewal deficiency in
      neural stem cells (NSCs). However, how nestin maintains self-renewal remains
      uncertain. Here, we used the dosage effect of nestin in heterozygous mice (Nes+/
      ) to study self-renewal of NSCs. With existing extracellular signaling in vivo or
      in vitro, nestin levels do not affect proliferation ability or apoptosis when
      compared between Nes+/- and Nes+/+ NSCs. However, self-renewal ability of Nes+/-
      NSCs is impaired when plated at a low cell density and completely lost at a
      clonal density. This deficiency in self-renewal at a clonal density is rescued
      using a medium conditioned by Nes+/+ NSCs. In addition, the Akt signaling pathway
      is altered at low density and reversed by conditioned medium. Our data show that
      secreted factors contribute toward maintaining self-renewal of NSCs by nestin,
      potentially through Akt signaling. 

PMID- 24918460
TI  - Decreased white matter integrity in mesial temporal lobe epilepsy: a machine
      learning approach.
AB  - Statistical analysis on diffusion tensor imaging has been used extensively in
      mesial temporal lobe epilepsy (mTLE) and most studies report decrease in
      fractional anisotropy (FA) in multiple white matter regions. However, these
      findings vary across studies and between regions. Therefore, in this study, we
      used tract-based spatial statistics along with machine learning approaches to
      investigate the whole-brain white matter changes between 17 left mTLE patients
      and 15 right mTLE patients and 34 matched healthy controls. The results showed
      that the three groups could be distinguished from each other with promising
      accuracy. Compared with controls, the FA value of the most discriminating voxels
      was decreased in the ipsilateral limbic system, corpus callosum, and temporal
      white matter in both patient groups. Compared with right mTLE, left mTLE had
      decreased FA in the left temporal white matter, whereas right mTLE had decreased
      FA in the right frontal and temporal white matter, and right posterior corona
      radiata. These findings not only provide useful information for lateralization of
      the seizure focus but can also be used as a potential biomarker for the diagnosis
      and treatment of the mTLE. This may be helpful in assessment of patients with
      mTLE when no lesion is detected on visual evaluation. 

PMID- 24918461
TI  - Is the hypothalamic-pituitary axis the central command for controlling fracture
      healing?

PMID- 24918462
TI  - Transplanted iNSCs migrate through SDF-1/CXCR4 signaling to promote neural
      recovery in a rat model of spinal cord injury: retraction.
AB  - The article by Ma et al. [Ma J, Li X, Yi B, Yao H, Zhao H, Zhang Y, et al.
      Transplanted iNSCs migrate through SDF-1/CXCR4 signaling to promote neural
      recovery in a rat model of spinal cord injury. Neuroreport 2014; 25:391-397]
      published in issue 6 of 2014 has been retracted by the Editors. This was owing to
      falsification of documentation that meant not all authors supported submission of
      the article for publication. The first author Jianhua Ma has accepted
      responsibility.

PMID- 24918463
TI  - Virtual single-source computed tomography using dual-source acquisition: a new
      technique for the dose-neutral intraindividual comparison of different scan
      protocols.
AB  - OBJECTIVES: The objective of this study was to compare the image quality of a
      standard single-source (SSS) computed tomography (CT) with that of a virtual
      single-source CT (VSS-CT) data set reconstructed from 2 raw data sets obtained by
      dual-source CT acquisition in abdominal CT to establish a radiation dose-neutral
      approach for the intraindividual comparison of 3 acquisition protocols at
      different radiation dose levels (RDLs). MATERIALS AND METHODS: An abdominal
      phantom representing an 80-kg male was imaged using dual-source CT (SOMATOM
      Definition; Siemens Healthcare) at 3 RDLs with 120 kV(p) and different tube
      currents (low, standard, and high milliampere-second protocol). For each RDL, raw
      data were obtained once in single-source mode using x-ray tube A only and 5 times
      in dual-source mode using different ratios for tube current of x-ray tubes A and
      B (same total radiation dose; A/B: 90%/10%, 80%/20%, 70%/30%, 60%/40%, 50%/50%).
      For each RDL, SSS-CT and 5 virtual single-source image data sets (VSS-CT50 - 90)
      were reconstructed. To compare SSS-CT and VSS-CT data sets, image quality was
      assessed in terms of high- and low-contrast performance by calculating the
      modulation transfer function, image noise, noise power spectrum, and, for low
      contrast lesion detectability, the modified multiscale structural similarity
      index (MS-SSIM*). A maximum decrease of Delta = 5% of image quality compared with
      SSS-CT was defined as acceptable, and a noninferiority analysis with Delta was
      performed. RESULTS: For modulation transfer function, noninferiority was observed
      for all VSS-CT data sets and RDL (P < 0.05). Image noise demonstrated an
      acceptable increase (<3.2%, P < 0.05) for each RDL and noise power spectrum
      showed only minor differences in the midfrequency range. The MS-SSIM* index
      demonstrated for the high RDL protocol a minor decrease for VSS-CT data sets
      (<2%, P < 0.05). For the standard and low RDL, the relative differences of the MS
      SSIM* index increased and were only in 1 case above Delta (standard RDL, mean VSS
      CT80 5.1%, P > 0.05). CONCLUSIONS: The image quality obtained by virtual and SSS
      reconstruction using equivalent total radiation exposure to the patient showed
      only negligible differences in image quality. Therefore, this technique might
      allow an intraindividual comparison of full and reduced radiation dose protocols
      within 1 image acquisition step by simply splitting the radiation dose between
      the 2 x-ray tubes of a dual-source CT.

PMID- 24918464
TI  - Seven-tesla magnetic resonance imaging of atherosclerotic plaque in the
      significantly stenosed carotid artery: a feasibility study.
AB  - OBJECTIVES: The objective of this study was to assess the feasibility of carotid
      vessel wall imaging at 7.0 for T magnetic resonance imaging (MRI) in a series of
      patients with a symptomatic greater than 70% stenosis of the internal carotid
      artery. MATERIALS AND METHODS: First, a series of 6 healthy volunteers were
      scanned at 3.0 T and 7.0 T MRI to perform a signal-to-noise ratio comparison
      between these 2 field strengths. Second, in patients with a greater than 70%
      stenosed carotid artery, a 7.0 T MRI protocol, consisting of a dual-echo turbo
      spin echo sequence (echo times of 45 and 150 milliseconds) and a T1-weighted
      turbo spin echo sequence, was obtained. Lumen and vessel wall were delineated for
      interobserver and intraobserver reproducibility, and signal intensity
      distribution in the most severely stenosed part of the internal carotid artery
      was correlated with different plaque components on histopathologic findings.
      RESULTS: The mean (SD) signal-to-noise ratio in the vessel wall was 42 (12) at
      7.0 T and 24 (4) at 3.0 T. Nineteen patients were included, but technical issues
      yielded carotid MRI data of 14 patients available for the final analysis. Of
      these patients, 4 were diagnosed with stroke, 7 were diagnosed with a transient
      ischemic attack, and 3 were diagnosed with amaurosis fugax. Intraclass
      correlation coefficient of the agreements of lumen and vessel wall determination
      between 2 observers and between the repeated measures of 1 observer were above
      0.80 in both 3.0 T and 7.0 T data sets of the healthy volunteers and also in the
      7.0 T data set of the patients. Signal hyperintensity in the 7.0 T magnetic
      resonance images was inversely proportional to calcification. Other correlations
      between plaque components and signal intensity could not be confirmed.
      CONCLUSIONS: This first series of patients with carotid atherosclerotic plaque
      who were scanned at 7.0 T MRI shows that 7.0 T MRI enables to adequately
      determine lumen and vessel wall areas. Signal hyperintensity in these 7.0 T
      magnetic resonance images was inversely proportional to calcification. However,
      at this stage, no other correlations between histologic findings and vessel wall
      contrast were found. Implementation of in vivo high-resolution 7.0 T MRI of
      plaque components for risk stratification remains challenging. Future development
      of hardware and software is still needed to attain a more robust setup and to
      enable complete plaque characterization, similar to what is currently possible
      with multiple MRI sequences at 1.5 T and 3.0 T MRI.

PMID- 24918465
TI  - Cystic gastrointestinal stromal tumors of the pancreas simulating
      cystoadenocarcinoma. Report of three cases and short review of the literature.
AB  - Gastrointestinal stromal tumors (GISTs) represent a distinct subset of
      mesenchymal tumours of the gastrointestinal tract. They are more common in the
      stomach and small intestine, and are characterized by the proliferation of
      spindle or epithelioid cells and by the expression of CD117. Extra
      gastrointestinal stromal tumors are rare and only 13 cases of pancreatic GISTs
      have been reported in the literature, only 1 of which presented as a cystic
      lesion. Mutational analysis of KIT and Platelet derived growth factor receptor
      alpha genes was performed only in two out of the 13 cases. We report 3 cases of
      cystic GISTs of the pancreas, radiologically mimicking a cystoadenocarcinoma.
      Routine histopathology and molecular characterization of the tumours have been
      performed. In two of them, molecular analysis showed unusual genetic alterations
      (the internal repeat of codon 502 and 503 in exon 9 of the KIT gene and the KIT
      exon 9 single nucleotide substitution c.1427G?T). Pancreatic GIST should be
      included in the differential diagnosis of both cystic and solid masses of the
      pancreas. The diagnosis should be accomplished by a combination of radiology,
      histology, immunohistochemistry and molecular biology. The evaluation of CD117
      expression and the sequence analysis of KIT and Platelet derived growth factor
      receptor-alpha gene is mandatory for therapy.

PMID- 24918466
TI  - Preparation and in vitro/in vivo evaluation of resveratrol-loaded carboxymethyl
      chitosan nanoparticles.
AB  - Resveratrol (RES) is natural polyphenol with a strong biological activity, but
      its disadvantages, such as poor water solubility, susceptibility to oxidative
      decomposition and rapid metabolism in the body, which substantially restricts in
      vivo bioavailability, need to be resolved. This study used carboxymethyl chitosan
      (CMCS) as a drug carrier and utilized emulsion cross-linking to prepare RES
      loaded CMCS nanoparticles (RES-CMCSNPs). A single-factor experiment was performed
      to optimize the preparation of these particles; in vitro and in vivo
      characteristics were evaluated. Spherical RES-CMCSNPs were prepared under optimal
      conditions, in which average particle size, potential, drug loading and
      encapsulation efficiency were (155.3 +/- 15.2) nm, (-10.28 +/- 6.4) mV, (5.1 +/-
      0.8)% and (44.5 +/- 2.2)%, respectively. FTIR, DSC and XRD showed that RES
      molecules were wrapped in the nanoparticles. In vitro DPPH radical scavenging
      abilities showed RES-CMCSNPs were better than RES raw powder. The nanoparticles
      improved the solubility of RES, thereby greatly improving the antioxidant
      activity of the drug. In vitro release experiments of RES and RES-CMCSNPs by
      simulating the human gastrointestinal tract were performed, in which RES-CMCSNPs
      rendered better releasing effects than raw RES. Raw RES and RES-CMCSNPs results
      were in line with those obtained for the single-chamber model for pharmacokinetic
      studies in rats. Compared with the bulk drugs, the RES-CMCSNPs exhibited
      increased in vivo absorption, prolonged duration of action and increased relative
      bioavailability by 3.516 times more than those of the raw RES. In addition, the
      residual chloroform is less than the ICH limit for class 2 solvents. 

PMID- 24918468
TI  - [Atypical human trypanosomoses].
AB  - Trypanosomes are principally responsible for two human diseases: human African
      trypanosomiasis (HAT) or sleeping sickness (caused by Trypanosoma brucei
      gambiense and T. b. rhodesiense), and Chagas disease, also called South American
      trypanosomiasis (T. cruzi). However, some trypanosomes that are natural parasites
      only of animals can sometimes infect humans and cause the so-called "atypical
      human trypanosomiases" (aHT). T. evansi, the agent causing surra in camels,
      horses, dogs, and bovines, and T. lewisi, a cosmopolite rat parasite, are the
      most frequently involved. These atypical infections involve no or only minor
      symptoms, but major symptoms are sometimes present. Parasite elimination is
      generally spontaneous, but can require treatment. Molecular tools, such as
      polymerase chain reaction, have improved the accuracy of parasite identification.
      Immunological techniques, mainly immunoenzymatic assays, can detect asymptomatic
      subjects. Several causes, most often concomitant, have been hypothesized,
      including immune immaturity, immunodeficiency, and close contact with infected
      animals. Innate immunity to animal trypanosomes depends on a trypanolytic factor
      called apolipoprotein L-I, present in human serum. A deficit in both
      apolipoprotein L-I alleles has been reported in an Indian patient infected by T.
      evansi. The prevalence of aHT is probably underestimated. Moreover, these
      trypanosomes might become potential emerging zoonotic pathogens, due to their
      ability to invade new hosts. An international network has been set up to survey
      these aHT (NAHIAT: Network on Atypical Human Infections by Animal Trypanosomes). 

PMID- 24918469
TI  - The ISBER strategic planning process and 2014 operating plan.

PMID- 24918470
TI  - Fusion surgery for recurrent cerebellar infarctions due to bilateral atlantoaxial
      rotational vertebral artery occlusion.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVE: To describe a unique
      case of recurrent cerebral embolisms with "bilateral" atlantoaxial rotational
      vertebral artery occlusion (RVAO), and review the literature on this rare entity.
      SUMMARY OF BACKGROUND DATA: The few reports of bilateral bow hunter's stroke
      (BHS) contain either RVAO at the subaxial level, and BHS associated with
      bilateral RVAO at the atlantoaxial level has never been reported. The treatment
      strategy for this entity is controversial. METHODS: An 18-year-old female
      experienced a cerebellar embolism in the left superior cerebellar artery area,
      followed by a second cerebral embolism in the right posterior inferior cerebellar
      artery area. Blood analysis showed no coagulation or autoimmune abnormalities.
      Transesophageal echocardiography ruled out a patent foramen ovale. Vertebral
      angiography and 3-dimensional computed tomography angiography with neck rotation
      clearly showed vertebral artery occlusion at the atlantoaxial level. For
      preventing a recurrence of thromboembolic event, surgical intervention was
      chosen. RESULTS: The patient underwent posterior atlantoaxial fixation with an
      iliac bone graft 2 months after the previous cerebellar infarction. Her
      postoperative course was uneventful. At 22 months of follow-up, she had no
      neurological deficits or further infarctions. Bony fusion was radiologically
      confirmed and 3-dimensional computed tomography angiography with neck rotation
      showed good patency of vertebral arteries. CONCLUSION: To our knowledge, the 7
      published reports of bilateral BHS or RVAO involve double causes both the
      atlantoaxial and subaxial levels, but 1 unspecified case. Because of the
      difficulty to identify the proper affected side in the case of bilateral
      atlantoaxial BHS with certainty, fusion surgery may be suitable for the reliable
      treatment. LEVEL OF EVIDENCE: N/A.

PMID- 24918472
TI  - Staphylococcus aureus hemolysin A disrupts cell-matrix adhesions in human airway
      epithelial cells.
AB  - Treatment of primary or immortalized human airway epithelial cells (16HBE14o-,
      S9) or alveolar cancer cells (A549) with recombinant hemolysin A (rHla), a major
      virulence-associated factor of Staphylococcus aureus, induces alterations in cell
      shape and formation of paracellular gaps in the cell layer. Semiquantitative
      Western blotting using extracts of freshly isolated airway tissue (nasal
      epithelium) or 16HBE14o- model cells revealed that phosphorylation levels of
      focal adhesion kinase (Fak) and paxillin were altered upon treatment of tissue or
      cells with rHla. Immune fluorescence analyses showed that rHla treatment of
      16HBE14o- cells results in losses of vinculin and paxillin from focal contacts
      and a net reduction in the number of focal contacts. The actin cytoskeleton was
      strongly remodeled. We concluded that treatment of cells with rHla activates Fak
      signaling, which accelerates focal contact turnover and prevents newly formed
      focal contacts (focal complexes) from maturation to focal adhesions. The
      inability of rHla-treated cells to form stable focal adhesions may be one factor
      that contributes to gap formation in the cell layer. In vivo, such changes may
      disturb the defensive barrier function of the airway epithelium and may
      facilitate lung infections by S. aureus. 

PMID- 24918473
TI  - Mediators and moderators of chronic pain outcomes in an online self-management
      program.
AB  - OBJECTIVES: Little is known about the moderators and mediators of change in
      online pain interventions based on cognitive-behavior therapy (CBT). We
      hypothesized that the effects of painACTION.com, an online pain self-management
      program, on pain-related outcomes would be mediated by changes in depression,
      anxiety, and stress, as well as the use of coping strategies. We also examined
      potential moderators of change. METHODS: First, the efficacy of painACTION.com
      and moderators of the intervention effects were evaluated using a pooled sample
      from previous back, neuropathic, and arthritis pain studies. Next, we explored
      whether the intervention effect on the primary outcomes, pain severity, and
      patient global impression of change (PGIC), was mediated by coping strategies or
      emotional functioning. RESULTS: Compared with controls, experimental participants
      evidenced significant improvement in pain, emotional functioning, and coping
      strategies from baseline to follow-up. There were no clear moderators of
      intervention effects. Changes in emotional factors, particularly stress levels,
      mediated the relationship between the intervention and outcome (pain severity)
      over time. DISCUSSION: This study supports the effectiveness of online
      interventions when CBT and self-management targets pain levels, emotional
      factors, and wellness-focused coping. The importance of stress as a mediator of
      pain severity is discussed. The absence of moderators may indicate that the
      intervention is effective for a wide variety of patients with chronic pain.

PMID- 24918474
TI  - The effect of neck-specific exercise with, or without a behavioral approach, on
      pain, disability, and self-efficacy in chronic whiplash-associated disorders: a
      randomized clinical trial.
AB  - OBJECTIVES: The aim of this study was to compare the effect on self-rated pain,
      disability, and self-efficacy of 3 interventions for the management of chronic
      whiplash-associated disorders: physiotherapist-led neck-specific exercise (NSE),
      physiotherapist-led NSE with the addition of a behavioral approach, or
      Prescription of Physical Activity (PPA). MATERIALS AND METHODS: A total of 216
      volunteers with chronic whiplash-associated disorders participated in this
      randomized, assessor blinded, clinical trial of 3 exercise interventions. Self
      rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck
      Disability Index), and self-efficacy (Self-Efficacy Scale) were evaluated at
      baseline and at 3 and 6 months. RESULTS: The proportion of patients reaching
      substantial reduction in pain bothersomness (at least 50% reduction) was more
      evident (P<0.01) in the 2 NSE groups (29% to 48%) compared with the PPA group
      (5%) at 3 months. At 6 months 39% to 44% of the patients in the 2 neck-specific
      groups and 28% in the PPA group reported substantial pain reduction. Reduction of
      disability was also larger in the 2 neck-specific exercise groups at both 3 and 6
      months (P<0.02). Self-efficacy was only improved in the NSE group without a
      behavioral approach (P=0.02). However, there were no significant differences in
      any outcomes between the 2 physiotherapist-led NSE groups. DISCUSSION: NSE
      resulted in superior outcomes compared with PPA in this study, but the observed
      benefits of adding a behavioral approach to the implementation of exercise in
      this study were inconclusive.

PMID- 24918475
TI  - Randomized placebo-controlled trial of sucrose analgesia on neonatal skin blood
      flow and pain response during heel lance.
AB  - OBJECTIVES: To evaluate the effect of oral sucrose on skin blood flow (SBF;
      perfusion units; PU) measured by Laser Doppler Imager (LDI) in term newborns and
      pain response (Neonatal Infant Pain Scale score; NIPS score) during heel lance;
      (2) determine SBF changes during heel lance; and (3) the relationship between SBF
      and NIPS. MATERIALS AND METHODS: Term infants <=7 days old (n=56) undergoing
      routine heel lance were randomized to pretreatment with 2.0 mL oral 24% sucrose
      (n=29) or sterile water (n=27) in a double-blinded, placebo-controlled trial. SBF
      was assessed by LDI scans and NIPS scores at 10 minutes before lance, immediately
      after lancing, and 5 minutes after blood extraction. Mean SBF and median NIPS
      scores were compared between groups using General Linear Model or Kruskal-Wallis.
      Regressions examined the relationship between SBF immediately after heel lance
      and NIPS score. RESULTS: Mean SBF and median NIPS scores immediately after heel
      lance were lower in sucrose-treated infants (167.9+/-15.5 vs. 205.4+/-16.0 PU,
      P=0.09; NIPS 1 [interquartile range 0 to 4] vs. NIPS 3 [interquartile range 0 to
      6], P=0.02), although no significant difference in mean SBF. During heel lance
      NIPS score was predictive of SBF. An increase of 1 in NIPS score was associated
      with 11 PU increase in SBF (R=0.21; P=0.09) for sucrose, and 16 PU increase for
      placebo-treated infants (R=0.20; P=0.014). CONCLUSIONS: Increased SBF assessed by
      LDI is a pain response among term neonates after routine heel lance, which was
      not completely attenuated by oral sucrose administration. Increased SBF is
      associated with NIPS scores. Sucrose analgesic efficacy evidenced by decreased
      NIPS scores for the sucrose group. Association of SBF with NIPS scores suggests
      that LDI is potentially useful for assessing newborn procedural pain.

PMID- 24918476
TI  - Extra virgin olive oil phenols suppress migration and invasion of T24 human
      bladder cancer cells through modulation of matrix metalloproteinase-2.
AB  - The consumption of extra virgin olive oil (EVOO), a common dietary habit of the
      Mediterranean people, seems to be related to a lower incidence of certain types
      of cancer including bladder neoplasm. Metastases are the major cause of bladder
      cancer-related deaths and targeting cell motility has been proposed as a
      therapeutic strategy to prevent cancer spread. This study aimed to investigate
      the potential antimetastatic effect of total phenols extracted from EVOO against
      the human transitional bladder carcinoma cell line T24. We also aimed at
      verifying that EVOO extract exerts cytotoxic effect on tumor cells without
      affecting normal urothelial fibroblasts. Our results show that EVOO extract can
      significantly inhibit the proliferation and motility of T24 bladder cells in a
      dose-dependent manner. In the same experimental conditions fibroblast
      proliferation and motility were not significantly modified. Furthermore the
      enzymatic activity of MMP-2 was inhibited at nontoxic EVOO extract doses only in
      T24 cells. The qRT-PCR revealed a decrease of the MMP-2 expression and a
      simultaneous increase of the tissue inhibitors of metalloproteinases expression.
      Our results may support the epidemiological evidences that link olive oil
      consumption to health benefits and may represent a starting point for the
      development of new anticancer strategies. 

PMID- 24918477
TI  - Effects of flue gas compositions on nitrosamine and nitramine formation in
      postcombustion CO2 capture systems.
AB  - Amine-based technologies are emerging as the prime contender for postcombustion
      CO2 capture. However, concerns have arisen over the health impacts of amine-based
      CO2 capture associated with the release of nitrosamines and nitramines, which are
      byproducts from the reactions between flue gas NOx and solvent amines. In this
      study, flue gas compositions were systematically varied to evaluate their effects
      on the formation of nitrosamines and nitramines in a lab-scale CO2 capture
      reactor with morpholine as a model solvent amine. The accumulation of N
      nitrosomorpholine in both the absorber and washwater increased linearly with both
      NO and NO2 for concentrations up to ~20 ppmv. These correlations could be
      extrapolated to estimate N-nitrosomorpholine accumulation at extremely low NOx
      levels (0.3 ppmv NO2 and 1.5 ppmv NO). NO played a particularly important role in
      driving N-nitrosomorpholine formation in the washwater, likely following partial
      oxidation to NO2 by O2. The accumulation of N-nitromorpholine in both the
      absorber and washwater positively correlated with flue gas NO2 concentration, but
      not with NO concentration. Both N-nitrosomorpholine and N-nitromorpholine
      accumulated fastest in the absence of CO2. Flue gas humidity did not affect
      nitrosamine accumulation in either the absorber or the washwater unit. These
      results provide a basis for estimating the effects of flue gas composition on
      nitrosamine and nitramine accumulation in postcombustion CO2 capture systems. 

PMID- 24918478
TI  - Noninferiority Studies with Multiple New Treatments and Heterogeneous Variances.
AB  - The objective of a noninferiority (NI) trial is to affirm the efficacy of a new
      treatment compared with an active control by verifying that the new treatment
      maintains a considerable portion of the treatment effect of the control.
      Compensation by benefits other than efficacy is usually the justification for
      using a new treatment, as long as the loss of efficacy is within an acceptable
      margin (NI margin) from the standard treatment. A popular approach is to express
      this margin in terms of the efficacy difference between the new treatment and the
      active control. Based on this approach and the realization that NI trials often
      comprise several new treatments, statistical procedures that simultaneously
      conduct NI tests of several new treatments have been developed. However, these
      procedures rely on the assumption that the variances of the treatments are
      homogeneous. In this article, we discuss the undesirable effect of using these
      procedures on the familywise Type I error rate when the treatment responses have
      heterogeneous variances. To alleviate this problem, we reveal potential
      procedures that are more appropriate. Further, a power study is conducted to
      compare the different procedures to provide guidance on the selection of adequate
      testing procedures in NI trials. Clinical examples are given for illustrative
      purposes. 

PMID- 24918479
TI  - Coupled 3D time-dependent wave-packet approach in hyperspherical coordinates:
      application to the adiabatic singlet-state(1(1)A') D(+) + H2 reaction.
AB  - We explore a coupled three-dimensional (3D) time-dependent wave packet formalism
      in hyperspherical coordinates for a 4D reactive scattering problem on the lowest
      adiabatic singlet surface (1(1)A') of the D(+) + H2 reaction. The coupling among
      the wavepackets arises through quantization of the rotation matrix, which
      represents the orientation of the three particles in space. The required
      transformation from Jacobi to hyperspherical coordinates and vice versa during
      initialization and projection of the wave packet on the asymptotic state(s), and
      the coupled equations of motion, are briefly discussed. With the long-range
      potential known to contribute significantly on the D(+) + H2 system, we
      demonstrate the workability of our approach, where the convergence profiles of
      the reaction probability for the reactive noncharge transfer (RNCT) process [D(+)
      + H2(v=0, j=0,1) -> HD(v',j') + H(+)] are shown for three different collisional
      energies (1.7, 2.1, and 2.5 eV) with respect to the helicity (K) and total
      angular momentum (J) quantum numbers. The calculated reactive cross-section is
      presented as a function of the collision energy for two different initial states
      of the diatom (v = 0, j = 0, 1). 

PMID- 24918480
TI  - Cyclosporine treatment of angioimmunoblastic T-cell lymphoma relapsed after an
      autologous hematopoietic stem cell transplant.
AB  - An angioimmunoblastic T-cell lymphoma is a unique type of peripheral T-cell
      lymphoma; it has an aggressive course and a poor prognosis. There is no standard
      therapy for angioimmunoblastic T-cell lymphoma, especially for refractory or
      relapsed cases. Here, we report a case of 53-year-old woman with
      angioimmunoblastic T-cell lymphoma who underwent high-dose chemotherapy with an
      autologous hematopoietic stem cell transplant after several cycles of
      chemotherapy, but soon relapsed with severe autoimmune hemolytic anemia. The
      patient was given dexamethasone and thalidomide, but responded poorly; however,
      she responded well to cyclosporine and finally achieved a sustained response.
      Thus, we conclude that cyclosporine has an effect in relapsed angioimmunoblastic
      T-cell lymphoma after an autologous hematopoietic stem cell transplant. 

PMID- 24918481
TI  - A simple method of reducing residual intraperitoneal carbon dioxide after
      laparoscopic cholecystectomy: a prospective, randomized, controlled study.
AB  - PURPOSE: The aim of the current study was to directly investigate whether active
      gas suction reduces intraperitoneal residual carbon dioxide and to analyze the
      effect of active gas suction on postoperative pain after laparoscopic
      cholecystectomy. SUBJECTS AND METHODS: This prospective, randomized clinical
      study included patients between 19 and 65 years of age with gallbladder disease
      who were eligible for elective laparoscopic cholecystectomy. Patients were
      allocated into either the natural evacuation group (NE group) or the active
      suction group (AS group). In the AS group, active suction was applied by
      inserting the laparoscopic suction irrigation device through a 5-mm trocar for 60
      seconds at the end of surgery. A chest X-ray was taken at postoperative Day 1,
      and the residual intraabdominal gas volume was measured. Perioperative data
      including pain score and analgesic requirement were collected. RESULTS: Thirty
      nine patients were allocated to the NE group, and 36 were allocated to the AS
      group. There was no statistically significant difference between the two groups
      in terms of demographic data and operative findings. However, a significant
      difference was observed in the residual intraperitoneal gas volume, with 15.9+/
      6.8 mL in the NE group and 6.7+/-4.0 mL in the AS group (P<.001). Significant
      differences were also observed in the pain scores measured 6 hours after surgery,
      on postoperative Day 1, and on postoperative Day 2. CONCLUSIONS: Active gas
      suction is a very simple procedure that is safe and feasible. Performing this
      procedure significantly decreases the residual intraperitoneal gas volume and
      postoperative pain after laparoscopic surgery.

PMID- 24918482
TI  - Surfactant-induced phases in water-supported alkane monolayers: I.
      Thermodynamics.
AB  - Alkanes longer than n = 6 carbons do not spread on the water surface, but
      condense in a macroscopic lens. However, adding trimethylammonium-based
      surfactants, C(m)TAB, in submillimolar concentrations causes the alkanes to
      spread and form a single Langmuir-Gibbs (LG) monolayer of mixed alkanes and
      surfactant tails, which coexists with the alkane lenses. Upon cooling, this LG
      film surface-freezes at a temperature T(s) above the bulk freezing temperature
      T(b). The thermodynamics of surface freezing (SF) of these LG films is studied by
      surface tension measurements for a range of alkanes (n = 12-21) and surfactant
      alkyl lengths (m = 14, 16, 18), at several concentrations c. The surface freezing
      range T(s)-T(b) observed is up to 25  degrees C, an order of magnitude larger
      than the temperature range of SF monolayers on the surface of pure alkane melts.
      The measured (n,T) surface phase diagram is accounted for well by a model based
      on mixtures' theory, which includes an interchange energy term omega. omega is
      found to be negative, implying attraction between unlike species, rather than the
      repulsion found for SF of binary alkane mixtures. Thus, the surfactant/alkane
      mixing is a necessary condition for the occurrence of SF in these LG films. The X
      ray derived structure of the films is presented in an accompanying paper.

PMID- 24918483
TI  - A survey of interprofessional education in chiropractic continuing education in
      the United States.
AB  - Objective : The purpose of this study is to describe the state of chiropractic
      continuing education vis-a-vis interprofessional education (IPE) with medical
      doctors (MD) in a survey of a sample of US doctors of chiropractic (DC) and
      through a review of policies. Methods : Forty-five chiropractors with experience
      in interprofessional settings completed an electronic survey of their experiences
      and perceptions regarding DC-MD IPE in chiropractic continuing education (CE).
      The licensing bodies of the 50 US states and the District of Columbia were
      queried to assess the applicability of continuing medical education (CME) to
      chiropractic relicensure. Results : The majority (89.1%) of survey respondents
      who attend CE-only events reported that they rarely to never experienced MD-IPE
      at these activities. Survey respondents commonly attended CME-only events, and
      84.5% stated that they commonly to very commonly experienced MD-IPE at these
      activities. More than half (26 of 51) of the licensing bodies did not provide
      sufficient information to determine if CME was applicable to DC relicensure.
      Thirteen jurisdictions (25.5%) do not, and 12 jurisdictions (23.5%) do accept CME
      credits for chiropractic relicensure. Conclusion : The majority of integrated
      practice DCs we surveyed reported little to no IPE occurring at CE-only events,
      yet significant IPE occurring at CME events. However, we found only 23.5% of
      chiropractic licensing bodies allow CME credit to apply to chiropractic
      relicensure. These factors may hinder DC-MD IPE in continuing education. 

PMID- 24918484
TI  - Synthesis and late-stage functionalization of complex molecules through C-H
      fluorination and nucleophilic aromatic substitution.
AB  - We report the late-stage functionalization of multisubstituted pyridines and
      diazines at the position alpha to nitrogen. By this process, a series of
      functional groups and substituents bound to the ring through nitrogen, oxygen,
      sulfur, or carbon are installed. This functionalization is accomplished by a
      combination of fluorination and nucleophilic aromatic substitution of the
      installed fluoride. A diverse array of functionalities can be installed because
      of the mild reaction conditions revealed for nucleophilic aromatic substitutions
      (S(N)Ar) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution
      versus the rates for competitive processes provides a framework for planning this
      functionalization sequence. This process is illustrated by the modification of a
      series of medicinally important compounds, as well as the increase in efficiency
      of synthesis of several existing pharmaceuticals.

PMID- 24918485
TI  - Medical costs and productivity losses of cancer survivors--United States, 2008
      2011.
AB  - The number of persons in the United States with a history of cancer has increased
      from 3 million in 1971 to approximately 13.4 million in 2012, representing 4.6%
      of the population. Given the advances in early detection and treatment of cancer
      and the aging of the U.S. population, the number of cancer survivors is projected
      to increase by >30% during the next decade, to approximately 18 million. Cancer
      survivors face many challenges with medical care follow-up, managing the long
      term and late effects of treatments, monitoring for recurrence, and an increased
      risk for additional cancers. These survivors also face economic challenges,
      including limitations in work and daily activities, obtaining health insurance
      coverage and accessing health care, and increasing medical care costs. To
      estimate annual medical costs and productivity losses among male and female
      cancer survivors and persons without a cancer history, CDC, along with other
      organizations, analyzed data from the 2008-2011 Medical Expenditure Panel Survey
      (MEPS), sponsored by the Agency for Healthcare Research and Quality. The results
      indicate that the economic burden of cancer survivorship is substantial among all
      survivors. For male cancer survivors, during 2008-2011, average annual medical
      costs and productivity losses resulting from health problems per person and
      adjusted to 2011 dollars were significantly higher among cancer survivors than
      among persons without a cancer history, by $4,187 and $1,459, respectively; for
      females, the estimated annual costs per person were $3,293 and $1,330 higher
      among cancer survivors than among persons without a cancer history, respectively.
      These findings suggest the need to develop and evaluate health and employment
      intervention programs aimed at improving outcomes for cancer survivors and their
      families. 

PMID- 24918486
TI  - Progress toward measles elimination--Eastern Mediterranean Region, 2008-2012.
AB  - In 1997, the 22 countries in the World Health Organization (WHO) Eastern
      Mediterranean Region (EMR) adopted a goal of measles elimination by 2010. To
      achieve this goal, the WHO Regional Office for the Eastern Mediterranean Region
      (EMRO) developed a four-pronged strategy: 1) achieve >= 95% vaccination coverage
      of children with the first dose of measles-containing vaccine (MCV1) in every
      district of each country through routine immunization services, 2) achieve >= 95%
      vaccination coverage with the second dose of measles-containing vaccine (MCV2) in
      every district of each country either through a routine 2-dose vaccination
      schedule or through supplementary immunization activities (SIAs), 3) conduct high
      quality, case-based surveillance in all countries, and 4) provide optimal
      clinical case management, including supplementing diets with vitamin A. Although
      significant progress was made toward measles elimination in the EMR during 1997
      2007, the measles elimination goal was not reached by the target date of 2010,
      and the date was revised to 2015. This report updates previous reports and
      summarizes the progress made toward measles elimination in EMR during 2008-2012.
      From 2008 to 2012, large outbreaks occurred in countries with a high incidence of
      measles, and reported annual measles cases in EMR increased from 12,186 to
      36,456. To achieve measles elimination in EMR, efforts are needed to increase 2
      dose vaccination coverage, especially in countries with high incidence of measles
      and in conflict-affected countries, and to implement innovative strategies to
      reach populations at high risk in areas with poor access to vaccination services
      or with civil strife.

PMID- 24918487
TI  - Knowledge, attitudes, and practices regarding antimalarial chemoprophylaxis in
      U.S. Peace Corps Volunteers--Africa, 2013.
AB  - Long-term travelers to areas where malaria is endemic are at risk for this
      potentially fatal disease; however, malaria can be prevented through the use of
      insecticide-treated bednets, mosquito repellents, and chemoprophylaxis. Three
      options for chemoprophylaxis are available in the Africa region: mefloquine,
      doxycycline, and atovaquone-proguanil. These options differ by dosing regimen,
      cost, and side effect profile. Long-term adverse effects of these drugs have been
      reported rarely. 

PMID- 24918488
TI  - N-acetyl-beta-glucosaminidase urine activity as a marker of early proximal tubule
      damage and a predictor of the long-term function of the transplanted kidneys.
AB  - INTRODUCTION: Ischaemia-reperfusion injury (IRI) is a factor leading to the
      damages of the transplanted kidney, what affects mainly the proximal tubules.
      Early monitoring of tubule damage can be an efficient tool to predict the
      allograft dysfunction. Present in proximal tubules, N-acetyl-beta-glucosaminidase
      (NAG) is a lysosomal enzyme whose excretion rises as a result of IRI or acute
      rejection. The aim of this study was to monitor the NAG urine activity to
      evaluate the early proximal tubule damage, and to try to predict the long-term
      function of the transplanted kidney. MATERIAL AND METHODS: The study enrolled 87
      Caucasian renal transplant recipients (61.7% males, 38.3% females, mean age
      45.56+/-14.34 years). Urine samples were collected for NAG and creatinine
      analysis on the 1st day after transplantation, and then in the 3rd and 12th
      month. Protocol biopsies were performed in the 3rd and 12th month. RESULTS: A
      significant positive correlation between NAG urine activity in the 3rd month
      after transplantation and creatinine concentration on the 14th (p=0.004) and 30th
      day (p=0.05), in the 3rd month (p=0.009) and after the 1st (p=0.005) and 2nd year
      (p=0.003) was observed. A statistically significantly higher urinary NAG activity
      in samples collected in the first 3 days and in the 3rd month after
      transplantation among patients with DGF (p=0.006 and p=0.03 respectively) was
      found. There was a significant positive correlation between NAG urine activity in
      the 3rd month and the grade of tubular atrophy in specimens collected in the 3rd
      (p=0.03) and 12th (p=0.04) month. CONCLUSIONS: Monitoring of NAG urine activity
      is useful in the evaluation of early proximal tubule damage and predicting the
      long-term function of the transplanted kidneys.

PMID- 24918489
TI  - A proteomics approach to identify the differential protein level in cardiac
      muscle of diabetic rat.
AB  - BACKGROUND: Cardiovascular proteomics investigation reveals the characterization
      and elucidation of the novel therapeutic targets and strategies to prevent the
      development of heart failure associated diabetic complication by using 2DE and
      MS. METHODS: The experimental animals were made diabetic with a single
      intraperitoneal injection of alloxan (150 mg/kg of bw). Albino rats were randomly
      divided into four individual groups: Group-I control (n=6), group-II alloxan
      induced diabetic rats, untreated (n=6), group-III (n=6) and group-IV (n=6)
      alloxan-induced diabetic rats were treated with aqueous and ethanolic extracts of
      Cynodon dactylon for 15 days, respectively. Animals were euthanized to collect
      the heart tissues and blood samples. 2DE sample preparation, gel running and
      staining (n=6: each groups) were performed at the same time to avoid variation.
      The result of six gel images from each group were analyzed and evaluated as one
      match set with 2D software (P<0.05). RESULTS: The above experiment revealed two
      up-regulated proteins in group-II i.e. NTF4 and ETFB. CONCLUSIONS: NTF4 is a
      neuro-protective agent for neuro-degenerative diseases. It will prevent diabetic
      secondary complications, such as diabetic polyneuropathy and cardiomyopathy. ETFB
      is active in the mitochondria, the energy-producing centres in cells. It is clear
      from the experiment that because of up-regulation of ETFB more energy is
      availabile and the electron transfer for heart during diabetes is possible, what
      leads to reduce the oxidative stress and free-radical formation. The up-regulated
      proteins reduced CVD that occurred just before overt hyperglycaemia due to
      administration of C. dactylon. This approach established the preliminary
      reference map for decoding cellular mechanisms linked between pathogenesis CVD
      and diabetes.

PMID- 24918490
TI  - Leonurus cardiaca L. herb--a derived extract and an ursolic acid as the factors
      affecting the adhesion capacity of Staphylococcus aureus in the context of
      infective endocarditis.
AB  - The objective was an assessment of the impact of Leonurus cardiaca L. extract
      (LCE) and ursolic acid (UA) on the adhesive properties of Staphylococus aureus
      NCTC 8325 strain, expressing virulence factors important in the pathogenesis of
      infective endocarditis. The adhesion and biofilm formation of bacteria cultured
      in the presence of subinhibitory concentrations of LCE or UA on the abiotic
      surface or covered with fibrinogen, fibronectin or collagen, were evaluated.
      Inhibitory effects of LCE and UA on staphylococcal adherence to both types of
      surface were demonstrated. This, in the case of UA, resulted in a significant
      reduction of biofilm formation. 

PMID- 24918491
TI  - Antigen-specific lymphocyte proliferation as a marker of immune response in
      guinea pigs with sustained Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) bacteria are human pathogens causing symptomatic
      gastritis, peptic ulcer or gastric cancer. Little is known about the kinetics of
      immune responses in H. pylori infected patients because the initial moment of
      infection has not been identified. Various animal models are used to investigate
      the immune processes related to H. pylori infection. In this study we checked
      whether H. pylori infection in guinea pigs, mimicking natural H. pylori infection
      in humans, resulted in the development of specific immune responses to H. pylori
      antigens by measuring the proliferation of lymphocytes localized in mesenteric
      lymph nodes, spleen and peripheral blood. The maturity of macrophages and
      cytokines, delivered by monocyte-macrophage lineage or lymphocytes, were
      considered as mediators, which might influence the lymphocyte blastogenic
      response. The obtained results showed the activation of T cells localized in
      mesenteric lymph nodes by H. pylori antigens in H. pylori infected guinea pigs
      four weeks postinfection. The blastogenic activity of lymphocytes was shaped by
      their interaction with antigen presenting cells, which were present in the cell
      cultures during the whole culture period. Moreover, the balance between cytokines
      derived from adherent leukocytes including interleukin 8--IL-8 as well as
      interferon gamma--IFN-gamma, and transforming growth factor beta--TGF-beta
      delivered by lymphocytes, was probably important for the successful proliferation
      of lymphocytes. The H. pylori specific lymphocytes were not propagated in
      peripheral blood and spleen of H. pylori infected animals. The modulation of
      immunocompetent cells by H. pylori antigens or their different distribution
      cannot be excluded.

PMID- 24918492
TI  - The effect of thyme and tea tree oils on morphology and metabolism of Candida
      albicans.
AB  - Members of Candida species cause significant problems in medicine and in many
      industrial branches also. In order to prevent from Candida sp. development,
      essential oils are more and more frequently applied as natural, non-toxic, non
      pollutive and biodegradable agents with a broad spectrum of antimicrobial
      activity. The aim of the research was to determine changes in morphology and
      metabolic properties of Candida albicans in the presence of thyme and tea tree
      oils. Changes of enzymatic activity of isolates were observed in the presence of
      both tested essential oils, and they were primarily associated with loss or
      decrease of activity of all enzymes detected for control. Furthermore, only for 3
      out of 11 isolates additional activity of N-acetyl-beta-glucosaminidase, alpha
      mannosidase, alpha-fucosidase and trypsin was detected. Vivid changes in
      biochemical profiles were found after treatment with tea tree oil and they were
      related to loss of ability to assimilate D-xylose, D-sorbitol and D-trehalose.
      The main differences in morphology of isolates compared to the control strain
      concerned formation of pseudohyphae structures. Both examined essential oils
      caused changes in cell and colony morphology, as well as in the metabolism of
      Candida albicans. However, the extent of differences depends on the type and
      concentration of an essential oil. The most important finding is the broad
      spectrum of changes in yeast enzymatic profiles induced by thyme and tea tree
      oils. It can be supposed that these changes, together with loss of ability to
      assimilate saccharides could significantly impact Candida albicans pathogenicity.

PMID- 24918494
TI  - Triterpene sapogenins with oleanene skeleton: chemotypes and biological
      activities.
AB  - Critical survey of a selected class of pentacyclic triterpenes--the oleanane
      family, is presented based on current literature in order to underline their
      value for medicinal chemistry and drug development potential. Oleanenes may be
      considered as a renewable resource of valuable research materials which are
      structurally diverse, inherently biocompatible and have built-in affinity for
      many categories of functional proteins. Although availability of particular
      compounds from natural sources may be very low, synthetic methods elaborated by
      generations of chemists, secure a way to obtaining desirable structures from
      commercial starting materials.

PMID- 24918493
TI  - High-grade mutant OmpF induces decreased bacterial survival rate.
AB  - OmpF plays very important roles in the influx of antibiotics and bacterial
      survival in the presence of antibiotics. However, high-grade mutant OmpF and its
      function in decreasing bacterial survival rate have not been reported to date. In
      the present study, we cloned a high-grade mutant OmpF (mOmpF) and sequence
      analysis suggested that over 45 percent of the DNA sequence was significantly
      mutated, leading to dramatic changes in over 55 percent of the amino acid
      sequence. mOmpF protein was successfully expressed. When grown in the presence of
      antibiotic, the bacterial survival rate decreased and the antibiotic inhibition
      zone became larger with the increase of the mOmpF. It was concluded that
      concentration of high-grade mutant mOmpF dramatically influenced the bacterial
      survival rate. The study presented here may provide insights into better
      understanding of the relationships between structure and function of OmpF. 

PMID- 24918495
TI  - Structural analysis of FeO(1 1 1)/Ag(0 0 1): undulation of hexagonal oxide
      monolayers due to square lattice metal substrates.
AB  - Iron oxide monolayers are grown on Ag(0 0 1) via reactive molecular beam epitaxy
      (metal deposition in oxygen atmosphere). The monolayer shows FeO stoichiometry as
      concluded from x-ray photoemission spectra. Both low energy electron diffraction
      as well as scanning tunneling microscopy demonstrate that the FeO layer has a
      quasi-hexagonal (1 1 1) structure although deposited on a surface with square
      symmetry. Compared to bulk values, the FeO(1 1 1) monolayer is unidirectionally
      expanded by 3.4% in [Formula: see text] directions while bulk values are
      maintained in [Formula: see text] directions. In [Formula: see text] directions,
      this lattice mismatch between FeO(1 1 1) monolayer and Ag(0 0 1) causes a
      commensurate undulation of the FeO monolayer where 18 atomic rows of the FeO(1 1
      1) monolayer match 17 atomic rows of the Ag(0 0 1) substrate. In [Formula: see
      text] directions, however, the FeO(1 1 1) monolayer has an incommensurate
      structure.

PMID- 24918496
TI  - Social patterning in grip strength, chair rise, and walk speed in an aging
      population: the Czech HAPIEE Study.
AB  - BACKGROUND: The aim was to examine the association of objective measures of
      physical functioning (PF) with education and material circumstances and the
      decline in PF with age by socioeconomic position (SEP). METHODS: In 3,205
      subjects (60-75 years) from the Czech Republic, we assessed relationship between
      PF, SEP, and age. Linear regression was used to assess PF measures and SEP
      measures. RESULTS: Cross-sectional decline in PF by age was similar in all
      individuals. Differences between SEP groups were similar across age groups,
      except for the difference in walk speed by material circumstances in men-bigger
      at older ages (p = .004). Men and women with the highest education were about 2 s
      faster at the chair rise test than those with the lowest education. DISCUSSION:
      Findings suggest strong educational gradient in PF, an inconsistent role of self
      assessed material circumstances, and virtually no interaction of SEP with the
      cross-sectional decline in PF by age.

PMID- 24918497
TI  - Resistant hypertension revisited: definition and true prevalence.

PMID- 24918498
TI  - Optimization of chondrocyte isolation and phenotype characterization for
      cartilage tissue engineering.
AB  - Current protocols for chondrocyte isolation are inconsistent, resulting in
      suboptimal cell yield and compromised cell quality. Thus, there is a need for an
      improved isolation protocol that is able to give a maximum yield with optimal
      cell viability while preserving the chondrocyte phenotype. In light of this, we
      developed an improved isolation protocol based on enzymatic digestion using 0.1%
      (w/v) collagenase II. Different from existing methods of digesting minced
      cartilage for a prolonged period (usually 14-16 h), we performed two additional
      digestions, with a 5- and 3-h interval in between. The results showed that this
      multiple digestion method was able to yield a total number of cells that are more
      than a fivefold increase as compared to any of the common isolation protocols.
      More importantly, a high percentage of the isolated cells remained viable.
      Furthermore, an evaluation of the effect of additional digestions on chondrocyte
      phenotype indicated that cells harvested from the second and third digestion
      showed a comparable or higher proliferative capacity than the first digestion and
      all the cells expressed chondrocyte-specific markers tested, with cells from the
      third digestion showing exceptionally high gene expression levels for collagen
      type II (Col II), aggrecan, and COMP. Additionally, their ability to produce
      collagen type II as well as their morphology were not affected by the two
      additional digestions. Taken together, the results suggested that the use of this
      isolation protocol resulted in a higher cell yield and the quality of the
      isolated cells was maintained. Hence, we recommend this isolation protocol to be
      employed for more efficient cell harvesting especially from limited biopsied
      cartilage tissue samples.

PMID- 24918499
TI  - Ultrafast carrier trapping of a metal-doped titanium dioxide semiconductor
      revealed by femtosecond transient absorption spectroscopy.
AB  - We explored for the first time the ultrafast carrier trapping of a metal-doped
      titanium dioxide (TiO2) semiconductor using broad-band transient absorption (TA)
      spectroscopy with 120 fs temporal resolution. Titanium dioxide was successfully
      doped layer-by-layer with two metal ions, namely tungsten and cobalt. The time
      resolved data demonstrate clearly that the carrier trapping time decreases
      progressively as the doping concentration increases. A global-fitting procedure
      for the carrier trapping suggests the appearance of two time components: a fast
      one that is directly associated with carrier trapping to the defect state in the
      vicinity of the conduction band and a slow one that is attributed to carrier
      trapping to the deep-level state from the conduction band. With a relatively long
      doping deposition time on the order of 30 s, a carrier lifetime of about 1 ps is
      obtained. To confirm that the measured ultrafast carrier dynamics are associated
      with electron trapping by metal doping, we explored the carrier dynamics of
      undoped TiO2. The findings reported here may be useful for the implementation of
      high-speed optoelectronic applications and fast switching devices. 

PMID- 24918500
TI  - Gold sputtered fiducial markers for combined secondary ion mass spectrometry and
      MALDI imaging of tissue samples.
AB  - Mass spectrometry imaging (MSI) is a label free technique capable of providing
      simultaneous identification and localization of biomolecules. A multimodal
      approach is required that allows for the study of the complexity of biological
      tissue samples to overcome the limitations of a single MSI technique. Secondary
      ion mass spectrometry (SIMS) allows for high spatial resolution imaging while
      matrix-assisted laser desorption (MALDI) offers a significantly wider mass range.
      The combination of coregistered SIMS and MALDI images results in detailed and
      unique biomolecular information. In this Technical Note, we describe how gold
      sputtered/implanted fiducial markers (FM) are created and can be used to ensure a
      proper overlay and coregistration of the two-dimensional images provided by the
      two MSI modalities. 

PMID- 24918501
TI  - Speech Language Pathology and Audiology.

PMID- 24918502
TI  - Influence of memory, attention, IQ and age on auditory temporal processing tests:
      preliminary study.
AB  - PURPOSE: To investigate the existence of correlations between the performance of
      children in auditory temporal tests (Frequency Pattern and Gaps in Noise--GIN)
      and IQ, attention, memory and age measurements. METHOD: Fifteen typically
      developing individuals between the ages of 7 to 12 years and normal hearing
      participated in the study. Auditory temporal processing tests (GIN and Frequency
      Pattern), as well as a Memory test (Digit Span), Attention tests (auditory and
      visual modality) and intelligence tests (RAVEN test of Progressive Matrices) were
      applied. RESULTS: Significant and positive correlation between the Frequency
      Pattern test and age variable were found, which was considered good (p<0.01,
      75.6%). There were no significant correlations between the GIN test and the
      variables tested. CONCLUSIONS: Auditory temporal skills seem to be influenced by
      different factors: while the performance in temporal ordering skill seems to be
      influenced by maturational processes, the performance in temporal resolution was
      not influenced by any of the aspects investigated.

PMID- 24918503
TI  - Correlation between the characteristics of resonance and aging of the external
      ear.
AB  - PURPOSE: Aging causes changes in the external ear as a collapse of the external
      auditory canal and tympanic membrane senile. Knowing them is appropriate for the
      diagnosis of hearing loss and selection of hearing aids. For this reason, the
      study aimed to verify the influence of the anatomical changes of the external ear
      resonance in the auditory canal in the elderly. METHODS: The sample consisted of
      objective measures of the external ear of elderly with collapse (group A), senile
      tympanic membrane (group B) and without changing the external auditory canal or
      tympanic membrane (group C) and adults without changing the external ear (group
      D). In the retrospective/clinical study were performed comparisons of measures of
      individuals with and without alteration of the external ear through the gain and
      response external ear resonant frequency and the primary peak to the right ear.
      RESULTS: In groups A, B and C was no statistically significant difference between
      Real Ear Unaided Response (REUR) and Real Ear Unaided Gain (REUG), but not for
      the peak frequency. For groups A and B were shown significant differences in REUR
      and REUG. Between the C and D groups were significant statistics to the REUR and
      REUG, but not for the frequency of the primary peak. CONCLUSION: Changes
      influence the external ear resonance, decreasing its amplitude. However, the
      frequency of the primary peak is not affected.

PMID- 24918504
TI  - Auditory brainstem response: reference-values for age.
AB  - PURPOSE: To study the absolute latencies of waves I , III and V and interpeak I
      III , III-V and I-V of Auditory brainstem responses obtained in preterm newborns
      in relation to post-conceptual age, term newborns and six months of age infants,
      establishing reference values for each age group. METHODS: Retrospective study
      realized through the analysis of tests performed on 80 infants divided into four
      groups, being the group one composed per newborns assessed between 35 and 36
      weeks post-conceptual age; group two by newborns assessed between 37 and 38
      weeks; group three with newborns reviewed between 39 to 40 weeks; and group four
      with infants evaluated with six months. RESULTS: The wave I absolute latency in
      the group one was 1.81 ms, decreasing to 1.79 ms in groups two and three, and to
      1.70 ms in group four. The wave III latency in group one was 4.74 ms, decreasing
      to 4.62 ms in group two, to 4.56 ms in the group three and to 4.37 ms in the
      group four. The wave V latency in group one was 7.14 ms, in the group two it was
      7.05 ms, in the group three 6.90 ms; and in the group four it was 6.50 ms.
      Interpeak latencies were also decreased in all groups. CONCLUSION: The latencies
      studied decreased with the increasing age and were similar values with the
      international literature.

PMID- 24918505
TI  - Intensive non-avoidance group therapy with stutterer adults: preliminary results.
AB  - PURPOSE: The purpose of the present study was to evaluate and document the use
      and efficacy of intensive non-avoidance group treatment for Bulgarian adults who
      stutter (AWS), to specify that changes are adopted in different speech situations
      (in the stabilization phase), and to demonstrate that changes are maintained
      after intensive therapy. METHODS: Participants were AWS (n=15, 12 males) with an
      average age of 25.2 years) Bulgarian native-speakers. Twelve participants were
      University students and three were clients with tertiary education in different
      areas. All participants were enrolled in First (overall effect) and Second
      (interim effect) Stages of Intensive Non-Avoidance Treatment for Stuttering. Van
      Riper's stuttering modification therapy approach was employed; the latter
      considers a non-avoidance treatment for stuttering. The treatment was conducted
      in participants' native Bulgarian language. RESULTS: AWS, as a group (n=15),
      significantly decreased the number of stuttered utterances after intensive
      treatment; findings were consistent for participants with moderate as well as
      severe stuttering. Likewise, there was a significant decrease in duration (in
      seconds) of disfluencies after treatment; findings were consistent for
      participants with moderate as well as severe stuttering. Eighty percent of AWS
      used cancellation immediately and six months after treatment, 65% mastered
      preparatory sets immediately and six months after treatment, 35% exhibited pull
      outs immediately after treatment and 55%, six months post-treatment. CONCLUSION:
      These preliminary findings were taken to suggest that intensive non-avoidance
      treatment for stuttering can be successfully employed with Bulgarian adults who
      stutter. Special focus was on the positive fluency changes that occurred during
      the course of therapy regarding the duration of disfluencies in seconds, and
      index of disfluencies.

PMID- 24918506
TI  - Adaptation of Clinical Evaluation of Language Functions--4th Edition to Brazilian
      Portuguese.
AB  - PURPOSES: To translate and adapt the Clinical Evaluation of Language Functions-
      4th Edition (CELF-4) to Brazilian Portuguese. METHOD: One hundred and sixty
      normal language development school children between the ages of seven and ten,
      half from public schools and the other half from private schools, both located on
      the east side of Sao Paulo. RESULTS: CELF-4's translation and adjustment to
      Brazilian Portuguese language showed equivalence between the original and
      translated versions, which demonstrates that there were no significant changes in
      the test's form and content. Cronbach's alpha test was used in order to verify
      CELF-4's subtests internal consistency, in other words, if every subtest measures
      consistently the evaluated constructors. In this analysis, we observed that by
      excluding right or wrong items, and problematic items from the pool (those
      different from the rest of the group), all analyzed subtest presented
      satisfactory internal consistency, except for the Word Association Task for eight
      years old. CONCLUSION: Most subtests, as well as the Pragmatic Profile and the
      Observational Evaluation Scale, were simply translated, dismissing significant
      adaptations. The alterations performed were due to morphosyntactic and
      phonological differences between both languages. CELF-4's translated and adapted
      version to Brazilian Portuguese was able to characterize the language performance
      in the studied population.

PMID- 24918507
TI  - Adaptation of the Child Development Clinical Risk Indicators instrument to
      retrospective parent report.
AB  - PURPOSE: To adapt the Child Development Clinical Risk Indicators (IRDI)
      instrument to retrospective report for parents of children from 3 to 7 years old
      and administer it in two groups. METHODS: Participated on the study 72 subjects-
      parents of children aged from 2 years and 11 months to 7 years and 7 months-
      divided into two groups: Research Group and Control Group. The proposed
      modification to parent report transformed the 31 indicators (affirmations) into
      retrospective self-administered questions to parents, with responses in Likert
      scale. The IRDI-questionnaire was administered in the two groups. RESULTS: The
      IRDI-questionnaire showed to be easy and quick to administer (average 15 minutes)
      and with low cost. The analysis of the questions obtained a good internal
      consistency value. The comparison between the groups by the parents' answers to
      the 31 questions showed difference in 16 questions. CONCLUSION: The items of the
      IRDI-questionnaire concern the main Autism Spectrum Disorders risk signs pointed
      out in literature. The parents' answers showed differences between the studied
      groups.

PMID- 24918508
TI  - Insertion and performance of Speech-Language Pathology and Audiology in Family
      Health Support Centers.
AB  - PURPOSE: To analyze the structure of the Centers for Supporting the Family Health
      (NASF), in 2010, identify the satisfaction degree of speech language pathologists
      who work in this area and compare the model proposed by the Brazilian Ministry of
      Health with practice. METHODS: Prospective and descriptive study, with 40 speech
      language pathologists inserted in NASF type one, from all Brazilian regions, in
      2010. It was used a questionnaire with nine questions related to different topics
      (work infrastructure, NASF team, actions developed by these professionals and
      satisfaction about the work), sent by electronic mail to the speech language
      pathologists. Descriptive statistics, chi2, ANOVA and Pearson coefficient of
      variation were used to analyze variables. Significance level of 5% was adopted.
      RESULTS: The speech language pathologists reported that, in their working places
      (NASF), there was an average of 12.2 Health Family Teams, with 8.9 professionals
      and 1.6 speech language pathologists. Most of them work 40 hours per week.
      Routine activities cited by speech language pathologists were: promotion and
      health prevention actions, matricial, therapies, support to health community
      workers, referrals, home visits, intersectoral actions and administrative tasks.
      There was variability in the satisfaction score: the majority of interviewees
      indicated the degree "Somewhat satisfied" for work infrastructure and referrals,
      as well as reported "Very satisfied" degree for home visits and support for
      health community workers. Comparing the model proposed by the Ministry of Health
      with the speech language pathologists' practices, there was no significant
      difference. The results show that 40% of speech language pathologists consider
      that the NASF actions are below the proposed model. CONCLUSION: The NASF
      structure varied in terms of the number of Family Health Teams, professionals
      involved and actions performed. There was also significant variability in the
      satisfaction degree among the subjects studied.

PMID- 24918509
TI  - Measuring noise in classrooms: a systematic review.
AB  - PURPOSE: The aim of this systematic review is to outline the main methodologies
      used for measuring noise in classrooms and if the noise levels found are suitable
      standards. METHODS: A survey of articles published in the last ten years, using
      six different databases. Were verified 1.088 publications and only eight studies
      met the inclusion criteria: (a) articles published in the last ten years, (b)
      articles available in full, (c) studies that have measured the noise in the
      classrooms of regular schools. DATA ANALYSIS: descriptive analysis was performed
      of selected publications. RESULTS: Five studies conducted to measure the noise
      using a sound level meter. One measurement performed using a dosimeter and two
      studies used a laptop with audio recording software. In all classrooms, the noise
      level was higher than allowed. CONCLUSION: Classrooms are noisy environment and
      there is no standardization regarding the methodology that should be used to
      measure the noise in these places. Therefore, schools need to be guided
      constantly about the importance of acoustic adaptation in the classroom.

PMID- 24918510
TI  - Behavioral characteristics of dysphonic children: integrative literature review.
AB  - PURPOSE: Integrative review of the scientific literature about the behavioral
      characteristics of dysphonic children discussing profiled and their etiologic
      relationship with the voice disorder, seeking to define recommendations on the
      importance of analyzing the behavior of children in voice assessment. RESEARCH
      STRATEGY: Integrative review of articles published in the last 12 years, the
      Virtual Health Library. SELECTION CRITERIA: Set up the theme of "behavioral
      characteristics of dysphonic children" was selected the databases LILACS, IBECS,
      MEDLINE, Cochrane Library, SciELO and ISI Web of Science and the following
      inclusion criteria: original articles, publication year from 2000 and 2012,
      Portuguese, English and Spanish. DATA ANALYSIS: Among the 528 articles published
      childish voice and dysphonia, seven covered the topic researched and were
      included in the results. RESULTS: Observed that four papers studied the behavior
      of children with vocal nodules, one addressed the behavioral characteristics of
      children with various types of dysphonic vocal fold lesion and three correlated
      Attention Deficit Disorder / Hyperactivity and dysphonia. CONCLUSION: Not
      established a behavioral profile of children with vocal disorders, but the
      results were consistent recommendation for the importance of this analysis in the
      evaluation of dysphonia in children.

PMID- 24918511
TI  - Dysfunctions of the stomatognathic system and vocal aspects in Fahr disease: case
      report.
AB  - The aim of this study is to report the case of a patient with Fahr's Disease in
      order to describe the main stomatognathic and vocal changes that can be found in
      individuals with this disease. In order to establish the diagnosis, an assessment
      of the conditions of orofacial motor system and speech production, as well the
      efficiency of swallowing, was realized. Based on these assessments, there were
      difficulties in coordinating and sustaining muscle during speech and presence of
      oropharyngeal dysphagia. Speech disorders found in Fahr's disease manifest
      themselves in complex and cover various aspects of phonological knowledge and the
      diseases that affect the basal ganglia have similar frames of speech-language
      disorders of the stomatognathic system, being able to present a picture of
      dysarthria. 

PMID- 24918512
TI  - Neuroradiology and voice findings in stroke.
AB  - Neurological dysphonias are vocal disorders followed by injuries or changes in
      the nervous system. Stroke is the second leading cause of death worldwide and the
      brain damage caused by it can affect communication in several aspects. The
      changes in the vocal features caused by these lesions are poorly described
      regarding the location and extent of cerebral involvement. The aim of this study
      was to describe vocal parameters of ten elderly patients affected by stroke
      according to the topography of the lesion at neuroimaging. We recorded from them:
      perceptual and auditory evaluation of voice and laryngeal diadochokinesis.
      Neuroimaging studies were classified according to location, extent, laterality
      territory of brain injury. The results show a population of extensive middle
      cerebral artery strokes and strokes with varied location in the brain. The
      subjects' voices showed predominantly the presence of roughness, breathiness,
      richeness and instability, and change in laryngeal motor control, demonstrated by
      reduced speed and instability in laryngeal diadochokinesis. These features
      presented in patients with extensive middle cerebral artery stroke and in
      patients with short strokes with varied location in the brain. The results
      suggest that the vocal features in the assessed cases do not depend only on the
      topography of the brain damage. Thus, it is important to consider the patient as
      unique in clinical evaluation. 

PMID- 24918513
TI  - Extended Neuralgic Amyotrophy Syndrome: voice therapy in one case of vocal fold
      paralysis.
AB  - Neuralgic Amyotrophy (NA) is a rare disturb of the peripheral nervous system that
      can include extreme pain, multifocal paresis and atrophy of the muscles of the
      upper limbs. When the nerves located outside of the brachial plexus are involved,
      the term Neuralgic Amyotrophy Extended (ANE) is used. Diagnosis of NA is clinical
      and has a series of inclusion and compatibility criteria established by the
      European CMT Consortium. On this study the clinical history, multidimensional
      vocal assessment data and the vocal techniques used in five-weeks voice therapy
      for one patient, professional voice, with ANE are presented. In this case, sudden
      and recurrent paralysis of his right vocal fold was the only manifestation of the
      disease. At the end of the fifth week the patient's voice was normal, the spoken
      and sung vocal ranges were same as before the current episode of ANE and scores
      of his vocal self-assessment were appropriate. 

PMID- 24918514
TI  - Defining infidelity in research and couple counseling: a qualitative study.
AB  - Infidelity can destroy relationships, but there is long-standing debate in the
      field about how best to define the construct. A clear definition of infidelity is
      important theoretically, empirically, and therapeutically; however, research on
      the topic is limited. This study explores how seven experienced couple counselors
      define infidelity on the basis of their work with heterosexual couples presenting
      with this issue. Thematic analysis was used to analyze interview transcripts and
      research findings suggest a rich web of conflicting definitions of infidelity for
      couples counselors and, in their accounts, clients. The findings support an
      understanding of infidelity as socially constructed and the implications of this
      for the field are discussed. 

PMID- 24918516
TI  - The effect of La2O3 in Tm3+-doped germanate-tellurite glasses for ~2 MUm
      emission.
AB  - A germanate-tellurite glass (GeO2-TeO2-K2O-Nb2O5-La2O3) with thulium doping has
      been investigated for application as a laser material around 2.0 MUm regions.
      Under the 808 nm laser diode pumped, intense 1.8 MUm emission is obtained. Based
      on the absorption spectra, radiative properties are predicted using Judd-Ofelt
      theory. The maximum value of emission cross-section of Tm(3+) around 1.8 MUm can
      reach 1.46 * 10(-20) cm(2), which indicated that the germanate-tellurite glass
      may provide high gain as a good medium for efficient 1.8 MUm laser system.

PMID- 24918518
TI  - Lack of association between APOE gene polymorphisms and amyotrophic lateral
      sclerosis: a comprehensive meta-analysis.
AB  - Several studies have evaluated the association between APOE gene polymorphisms
      and the risk for amyotrophic lateral sclerosis (ALS), with inconclusive results.
      The aim of our study was to further define the risk associated with carriage of
      the APOE alleles and development and clinical characteristics of ALS. We
      performed a comprehensive meta-analysis of all existing studies investigating the
      association between the APOE gene and ALS published up to September 2013,
      comprising a total of 4249 ALS patients and 10,397 controls. Pooled odds ratios
      (OR) were estimated using the random effect (RE) model. Results showed that the
      carriage of different APOE alleles had no effect on disease risk. In particular,
      the epsilon4 allele was not associated with a significantly increased disease
      risk (epsilon4 carriers vs. non-epsilon4 carriers: RE OR 1.18; 95% CI 0.91-1.53).
      In conclusion, our study suggests that the APOE gene does not have a significant
      effect in ALS aetiopathogenesis.

PMID- 24918517
TI  - Mental Health and Self-directed Violence Among Student Service Members/Veterans
      in Postsecondary Education.
AB  - OBJECTIVES: Using a sample of student service members/veterans, the current study
      aimed to examine the prevalence of psychiatric diagnoses and suicide-related
      outcomes and the association of hazardous duty with mental health. PARTICIPANTS:
      Data are from the Fall 2011 National College Health Assessment (N = 27,774).
      METHODS: Logistic regression was used to examine (1) the association of student
      service member/veteran status with mental health outcomes and (2) the association
      of hazardous duty with mental health outcomes among student service
      members/veterans (n = 706). RESULTS: Student service members/veterans had higher
      odds of self-harm than students without military experience. Among student
      service members/veterans, hazardous duty was positively associated (odds ratio
      [OR] = 2.00, 95% confidence interval [CI] [1.30, 3.07]) with having a psychiatric
      diagnosis but negatively associated (OR = 0.41, 95% CI [0.20, 0.85]) with
      suicidal ideation. CONCLUSIONS: Self-harm may be a unique phenomenon among
      service members/veterans. Suicide prevention with this population should include
      information about self-harm, and future research should explore whether suicidal
      intent underlies self-harm.

PMID- 24918519
TI  - Shear induced fabrication of intertwined single walled carbon nanotube rings.
AB  - Thin film microfluidic shearing of a mixture of toluene dispersed single walled
      carbon nanotubes (SWCNTs) and water in a vortex fluidic device results in SWCNT
      nanorings (and related structures), diameters 100 to 200 nm or 300 to 700 nm, for
      respectively 10 mm or 20 mm diameter rotating tubes. 

PMID- 24918520
TI  - Internalizing disorders and quality of life in adolescence: evidence for
      independent associations.
AB  - OBJECTIVE: To investigate whether internalizing disorders are associated with
      quality of life (QoL) in adolescents, even after accounting for shared risk
      factors. METHODS: The sample comprised 102 adolescents from a community cross
      sectional study with an oversampling of anxious subjects. Risk factors previously
      associated with QoL were assessed and divided into five blocks organized
      hierarchically from proximal to distal sets of risk factors. RESULTS: Multiple
      regression analysis yielded a hierarchical model accounting for 72% of QoL
      variance. All blocks were consistently associated with QoL (p < 0.05), accounting
      for the following percentages of variance: 12% for demographics; 5.2% for family
      environment; 37.8% for stressful events; 10% for nutritional and health habits;
      and 64.2% for dimensional psychopathological symptoms or 22.8% for psychiatric
      diagnoses (dichotomous). Although most of the QoL variance attributed to
      internalizing symptoms was explained by the four proximal blocks in the
      hierarchical model (43.2%), about 21% of the variance was independently
      associated with internalizing symptoms/diagnoses. CONCLUSIONS: QoL is associated
      with several aspects of adolescent life that were largely predicted by our
      hierarchical model. Our findings reinforce the hypothesis that internalizing
      disorders and internalizing symptoms in adolescents have a high impact on QoL and
      deserve proper clinical attention.

PMID- 24918521
TI  - Parameters for screening music performance anxiety.
AB  - OBJECTIVE: To assess the discriminative capacity of the Kenny Music Performance
      Anxiety Inventory (K-MPAI), in its version adapted for Brazil, in a sample of 230
      Brazilian adult musicians. METHOD: The Social Phobia Inventory (SPIN) was used to
      assess the presence of social anxiety indicators, adopting it as the gold
      standard. The Mann-Whitney U test and the receiver operating characteristic (ROC)
      curve were used for statistical analysis, with p <= 0.05 set as the significance
      level. RESULTS: Subjects with social anxiety indicators exhibited higher mean
      total K-MPAI scores, as well as higher individual scores on 62% of its items. The
      area under the ROC curve was 0.734 (p = 0.001), and considered appropriate.
      Within the possible cutoff scores presented, the score -15 had the best balance
      of sensitivity and specificity values. However, the score -7 had greater
      specificity and accuracy. CONCLUSION: The K-MPAI showed appropriate discriminant
      validity, with a marked association between music performance anxiety and social
      anxiety. The cutoff scores presented in the study have both clinical and research
      value, allowing screening for music performance anxiety and identification of
      possible cases.

PMID- 24918522
TI  - Industry withdrawal from psychiatric medication development.
AB  - Between 1950 and 1969, on a serendipitous basis, psychiatric drug development
      flourished. However, there has been a steep decline in the development of new
      medication classes. Instead of new molecular entities, slight molecular
      modifications producing "me-too" drugs attempted to garner market share. With
      failing profitability, industry is now withdrawing from psychiatric medication
      development. Managed care drastically shortened contact between patients and
      clinicians, so the possible observation of unexpected benefits has been
      nullified. The randomized, parallel-groups design met FDA requirements for
      specific pharmacological efficacy. However, it does not determine whether a
      patient who improved while drug-treated required the drug or would have gotten
      better on his own. Further, pathophysiology benefit remains obscure. The major
      psychotropic drugs have no benefits for normal subjects. Their remarkable
      benefits must stem from a necessary interaction with a pathophysiological state.
      Therefore, understanding therapeutic benefit by treating normal subjects becomes
      unlikely. The claim that therapeutic knowledge in psychiatry proceeds from bench
      to bedside has proven vacuous, primarily because of our limited understanding of
      brain pathophysiology. The utility of the alternative intensive design for
      understanding diagnosis, therapeutic benefit, and pathophysiology is emphasized. 

PMID- 24918523
TI  - Septic encephalopathy: does inflammation drive the brain crazy?
AB  - Sepsis and the multiorgan dysfunction syndrome are among the most common reasons
      for admission to an intensive care unit, and are a leading cause of death. During
      sepsis, the central nervous system (CNS) is one of the first organs affected, and
      this is clinically manifested as sepsis-associated encephalopathy (SAE). It is
      postulated that the common final pathway that leads to SAE symptoms is the
      deregulation of neurotransmitters, mainly acetylcholine. Thus, it is supposed
      that inflammation can affect neurotransmitters, which is associated with SAE
      development. In this review, we will cover the current evidence (or lack thereof)
      for the mechanisms by which systemic inflammation interferes with the metabolism
      of major CNS neurotransmitters, trying to explain how systemic inflammation
      drives the brain crazy. 

PMID- 24918524
TI  - Association study between the MDR1 gene and clinical characteristics in
      schizophrenia.
AB  - OBJECTIVE: Schizophrenia is a complex psychiatric disorder, characterized by
      disturbed patterns of thought and affecting 0.3-2.0% of the world population.
      Previously, the multidrug resistance 1 (MDR1) gene has been associated with
      schizophrenia in treatment response studies in psychotic patients. The aim of
      this study was to determine the association between MDR1 gene polymorphisms and
      clinical characteristics in patients with schizophrenia. METHODS: Positive and
      negative symptoms of schizophrenia were assessed with the Scale for the
      Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of
      Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of
      MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate
      ANOVA was performed with MDR1 polymorphisms and gender as independent variables.
      RESULTS: Males with the G/G genotype of MDR1 rs2032582 presented significantly
      higher levels of delusions (p = 0.02). When comparing female vs. male groups, the
      difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene
      rs1045642 variant showed no significant differences. CONCLUSION: Our findings
      suggest that male carriers of the G allele of variant rs2032582 exhibit greater
      severity of delusions; however, these results should be taken as preliminary, and
      replication studies in other populations of different ethnic origins are required
      to confirm these findings.

PMID- 24918525
TI  - The link between cardiovascular risk, Alzheimer's disease, and mild cognitive
      impairment: support from recent functional neuroimaging studies.
AB  - OBJECTIVE: To review functional neuroimaging studies about the relationship
      between cardiovascular risk factors (CVRFs), Alzheimer's disease (AD), and mild
      cognitive impairment (MCI). METHODS: We performed a comprehensive literature
      search to identify articles in the neuroimaging field addressing CVRF in AD and
      MCI. We included studies that used positron emission tomography (PET), single
      photon emission computerized tomography (SPECT), or functional magnetic resonance
      imaging (fMRI). RESULTS: CVRFs have been considered risk factors for cognitive
      decline, MCI, and AD. Patterns of AD-like changes in brain function have been
      found in association with several CVRFs (both regarding individual risk factors
      and also composite CVRF measures). In vivo assessment of AD-related pathology
      with amyloid imaging techniques provided further evidence linking CVRFs and AD,
      but there is still limited information resulting from this new technology.
      CONCLUSION: There is a large body of evidence from functional neuroimaging
      studies supporting the hypothesis that CVRFs may play a causal role in the
      pathophysiology of AD. A major limitation of most studies is their cross
      sectional design; future longitudinal studies using multiple imaging modalities
      are expected to better document changes in CVRF-related brain function patterns
      and provide a clearer picture of the complex relationship between aging, CVRFs,
      and AD.

PMID- 24918526
TI  - Glucose positions affect the phloem mobility of glucose-fipronil conjugates.
AB  - In our previous work, a glucose-fipronil (GTF) conjugate at the C-1 position was
      synthesized via click chemistry and a glucose moiety converted a non-phloem
      mobile insecticide fipronil into a moderately phloem-mobile insecticide. In the
      present paper, fipronil was introduced into the C-2, C-3, C-4, and C-6 positions
      of glucose via click chemistry to obtain four new conjugates and to evaluate the
      effects of the different glucose isomers on phloem mobility. The phloem mobility
      of the four new synthetic conjugates and GTF was tested using the Ricinus
      seedling system. The results confirmed that conjugation of glucose at different
      positions has a significant influence on the phloem mobility of GTF conjugates. 

PMID- 24918528
TI  - A Novel "Maximizing Kappa" Approach for Assessing the Ability of a Diagnostic
      Marker and Its Optimal Cutoff Value.
AB  - Threshold-dependent accuracy measures such as true classification rates in
      ordered multiple-class (k > 3) receiver operating characteristic (ROC) hyper
      surfaces have recently been used to assist with medical decision making. However,
      based on low power performance in some circumstances, we construct a new method
      that relies on the kappa coefficient to solve such diagnostic problems. Under the
      approach proposed in the present article, the statistics depend strongly on the
      [Formula: see text] cutoff threshold, which can be chosen to maximize the kappa
      statistics of true disease status and of the new biomarker. The Monte Carlo
      simulation results confirm the effectiveness of the proposed method in terms of
      its predictive power. The proposed design is then compared with the volume under
      the ROC hyper-surface by applying it to intracerebral hemorrhagic patients
      classified into five stroke classes using the National Institutes of Health
      Stroke Scale. 

PMID- 24918527
TI  - Genetic variations in IL1A and IL1RN are associated with the risk of preeclampsia
      in Chinese Han population.
AB  - Preeclampsia (PE) is an excessive systemic inflammation response with dysfunction
      of endothelial. Our study was to investigate the association between genetic
      variations in IL-1 and the susceptibility to PE in Chinese Han population. 402 PE
      patients and 554 normal pregnant women of third trimester were enrolled. The
      polymorphisms of rs315952 in IL1RN and rs17561 in IL1A were genotyped by TaqMan
      allelic discrimination real-time PCR. Obviously statistic difference of the
      genotypic frequencies were found in both of IL1RN rs315952 and IL1A rs17561
      between cases and controls (for rs315952, P = 0.001; for rs17561, P = 0.021.).
      For rs315952, the C allele was associated with development of PE (P = 0.003, OR =
      1.319, 95%CI 1.099-1.583). Patients with CC or CT genotype were less likely to
      develop severe PE than patients carrying TT genotype(P < 0.001, OR = 0.24, 95%CI
      0.15-0.40). For rs17561, the C allele was the risk factor for predisposition to
      PE (P = 0.012, OR = 1.496, 95%CI 1.089-2.055). Our results suggest IL1RN and IL1A
      may involve in the development of PE in Chinese Han population. 

PMID- 24918529
TI  - Is glycated hemoglobin related to other dysmetabolic variables implicated in the
      increase of cardiovascular risk in polycystic ovary syndrome? A comparative
      study.
AB  - BACKGROUND: In non-PCOS patients the concentration of glycated hemoglobin (HbA1C)
      has been employed to identify individuals at higher risk for impaired glucose
      tolerance (IGT) and diabetes mellitus. A few studies have examined the role of
      HbA1C in PCOS patients and current results are controversial. AIM: To compare the
      strength of the association between glycated hemoglobin and other predictors of
      cardiovascular risk in polycystic ovary syndrome (PCOS). METHODS: This cross
      sectional study enrolled 197 PCOS patients and 72 non-PCOS women. Transvaginal
      ultrasound, biochemical and hormone measurement were performed. Glycated
      hemoglobin (HbA1C) was correlated with other variables related to
      dysmetabolic/vascular diseases. RESULTS: The HbA1C levels were 6.0+/-1.4% and
      4.9+/-0.4% in PCOS patients and non-PCOS controls, respectively (p<0.001). The
      HbA1C levels were>=5.7% in 46.4% of PCOS and in none of the control subjects
      (OR=90.8). HbA1C was well-correlated with several anthropometric, metabolic and
      endocrine parameters. Stepwise multiple regression including HbA1C and other
      known predictors of cardiovascular risk resulted in a significant model in which
      body mass index (BMI) and free testosterone exhibited the best correlation with
      HbA1C (adjusted R(2)=0.530; F=39.8; p<0.001). CONCLUSION: HbA1C was elevated and
      correlated with anthropometric, biochemical and endocrine variables of
      metabolic/vascular disease risks in PCOS patients. Combined HbA1C, BMI and free
      testosterone levels provided a significant model with potential use to evaluate
      metabolic/vascular disease in PCOS patients.

PMID- 24918530
TI  - Costs of Diabetes Mellitus (CoDiM) in Germany, direct per-capita costs of
      managing hyperglycaemia and diabetes complications in 2010 compared to 2001.
AB  - INTRODUCTION: To identify direct health care costs of patients with diabetes in
      Germany in 2010, with focus on costs of treating hyperglycaemia and costs caused
      by diabetes complications, and to compare findings with results from the CoDiM
      study 2001. MATERIAL AND METHODS: The cost analysis was based on administrative
      data (18.75% random sample of 1.5 million insured persons). Medical costs covered
      by statutory health insurance and costs covered by nursing care insurance were
      included. Incremental differences in costs of patients with diabetes (n=30 987)
      and age and sex-matched subjects without a diagnosis of diabetes (controls) were
      estimated according to the number and type of complications. Costs were
      standardised to the German population. RESULTS: In 2010, incremental medical
      costs attributed to diabetes were ? 2 391 (95% confidence interval: 2 257-2 524)
      per patient with diabetes. Of that amount, 26.5% were spent for the management of
      hyperglycaemia (? 633 (622-644)) and 73.5% for the treatment of comp-lications (?
      1 758 (1 627-1 889)). Nursing care contributed incremental costs of ? 289 (249
      330), of which 98.8% was due to complications. From 2001 to 2010 the incremental
      per-capita costs for medical and nursing care decreased by 4.8% (controls:
      +3.9%), the per-capita costs for treating hyperglycaemia increased by 2.0% and
      the per-capita costs for complications decreased by 7.0%. CONCLUSION: Cost for
      diabetes is largely caused by management of complications. It is important to
      prevent complications by consequent management of diabetes as well as by primary
      prevention of its onset.

PMID- 24918531
TI  - Fasting blood glucose at admission and survival in patients with dilated
      cardiomyopathy: a single-center cohort study.
AB  - BACKGROUND: Recent data have suggested that impaired fasting glucose (IFG) is an
      independent risk factor for mortality in patients with heart failure. However,
      the prognostic indicator of elevated fasting blood glucose (FBG) such as IFG in
      dilated cardiomyopathy (DCM) was not well understood. The purpose of this study
      was to examine the association between IFG at admission and survival in
      hospitalized patients with DCM. METHODS: A retrospective cohort study was
      undertaken in 1 089 hospitalized patients with DCM in Fuwai Hospital from
      November 2003 to September 2 011 (female 26.5%, 51.4+/-14.6 years old). Standard
      demographics, echocardiography and routine blood samples were obtained shortly
      after admission. The outcomes were assessed using all-cause mortality at a mean
      follow-up of 3.5+/-2.3 years and were analyzed using Kaplan-Meier survival curve
      (log-rank test) and Cox regression. RESULTS: The cohort consisted of 1 089
      patients with DCM, 835 patients with normal fasting glucose (NFG, FBG<6.1 mmol/L,
      76.7%), 113 patients with IFG (FBG 6.1-6.9 mmol/L, 10.4%), and 141 patients with
      FBG>=7.0 mmol/L (12.9%). Among the 1 089 patients studied, 252 (23.1%) died over
      a mean follow-up period of 3.5+/-2.3 years. All-cause mortality rates were
      highest in patients with FBG>=7.0 mmol/L (31.2%), intermediate in those with IFG
      (24.8%), and lowest in those with NFG (21.6%); a significant difference in all
      cause mortality rate was found among the 3 groups (log-rank chi(2)=6.715,
      P=0.035). After adjustment for baseline variables, New York Heart Association
      (NYHA) functional class, QRS duration, left atrium diameter, systolic blood
      pressure, FBG>=7.0 mmol/L, not IFG, and circulating creatinine levels were the
      variables that remained as predictors of all-cause mortality. CONCLUSION: In the
      present study, all-cause mortality was higher in patients with FBG>=7.0 mmol/L
      compared to the patients with NFG, and FBG>= 7.0 mmol/L, not IFG, was one of
      predictors of all-cause mortality in DCM patients.

PMID- 24918532
TI  - High ghrelin levels in post-treatment euthyroid patients with Hashimoto's
      thyroiditis: a case-control preliminary study.
AB  - RATIONALE: Hashimoto's thyroiditis is a chronic inflammatory condition often
      associated with changes in appetite and body composition. Ghrelin is an
      orexigenic peptide involved in the regulation of appetite and food intake. A
      possible role of ghrelin in mediating inflammation has been suggested. A few
      contrasting published data are available on the relationship between thyroid
      status and circulating ghrelin in patients affected by Hashimoto's thyroiditis.
      The aim of the present case-control study was to provide additional evidence on
      the relationship between thyroid status and plasma ghrelin levels in post
      treatment euthyroid female patients with Hashimoto's thyroiditis, compared to
      healthy controls. METHODS: 25 women [age 46.6+/-10.6 years; Body Mass Index
      26.3+/-3.8 kg/m2] affected by overt hypothyroidism due to Hashimoto's thyroiditis
      were studied after thyroid hormones and body weight were already normalized for
      at least 2 months following L-thyroxine replacement. 25 healthy women (age 40.2+/
      6.4 years; Body Mass Index 26.2+/-4.0 kg/m2) served as the control group. Blood
      levels of thyroid hormones, thyroid peroxidase antibodies, thyroglobulin
      antibodies and ghrelin were determined. Fat mass, fat-free mass and high-density
      lipoprotein cholesterol were also assessed. RESULTS: Circulating ghrelin levels
      were significantly higher in patients vs. control subjects (p<0.001). No
      differences were found in metabolic parameters (body mass index, fat mass, fat
      free mass, high-density lipoprotein cholesterol) between groups. CONCLUSION: The
      present study provides additional evidence of hyperghrelinemia status in post
      treatment euthyroid patients affected by Hashimoto's thyroiditis.

PMID- 24918533
TI  - Effects of quercetin on oxidative stress biomarkers in methimazole - induced
      hypothyroid rats.
AB  - The objective of the present study was to evaluate the effect of quercetin on
      oxidative stress biomarkers in methimazole (MMI) - induced hypothyroidism male
      rats. Hypothyroidism was induced by administering MMI at 20 mg/100 ml in the
      drinking water, for 1 month. After achieved hypothyroidism, rats received orally
      10 or 25 mg/kg of quercetin (QT) for 8 weeks. 60 male wistar rats were randomly
      divided into 6 groups (group I, control; group II, QT10; group III, QT25; group
      IV, hypothyroid; group V, hypothyroid+QT10; group VI, hypothyroid+QT25). Liver,
      kidney and serum TBARS levels significantly increased in hypothyroid rats when
      compared to controls, along with increased protein carbonyl (PCO) in liver and
      increased ROS levels in liver and kidney tissues. QT10 and QT25 were effective in
      decreasing TBARS levels in serum and kidney, PCO levels in liver and ROS
      generation in liver and kidney. MMI - induced hypothyroidism also increased TBARS
      levels in cerebral cortex and hippocampus that in turn were decreased in rats
      treated with QT25. Moreover, the administration of QT25 to hypothyroid rats
      resulted in decreased SOD activities in liver and whole blood and increased liver
      CAT activity. Liver and kidney ascorbic acid levels were restored with quercetin
      supplementation at both concentrations. QT10 and QT25 also significantly
      increased total oxidative scavenging capacity in liver and kidney tissues from
      hypothyroid rats. These findings suggest that MMI - induced hypothyroidism
      increases oxidative stress parameters and quercetin administration could exert
      beneficial effects against redox imbalance in hypothyroid status.

PMID- 24918534
TI  - Serum omentin-1 levels in diabetic and nondiabetic patients with chronic kidney
      disease.
AB  - BACKGROUND: Omentin-1, a novel adipokine identified in visceral adipose tissue,
      is negatively correlated with different conditions such as diabetes, obesity and
      inflammation. However, changes in serum Omentin levels associated with the degree
      of the renal dysfunction and metabolic risk factors in CKD patients has not yet
      been revealed. In the present study, we aimed to investigate the level of Omentin
      1 and related para-meters in diabetic and non-diabetic CKD patients. METHODS: 64
      (30 diabetic, 34 non-diabetic) CKD patients and 27 healthy control subjects
      enrolled in this cross-sectional study. Anthropometric and laboratory assessment
      performed and malnutrition and inflammation components evaluated. Serum
      concentrations of Omentin-1 and insulin were measured by using ELISA. RESULTS:
      Serum Omentin-1 levels in CKD patients were significantly lower compared to the
      healthy controls. Further analyze revealed that decreased omentin in CKD patients
      was due to the reduced omentin levels in the diabetic subgroup. An increase in
      inflammation and malnutrition components was correlated with a decrease in the
      serum level of Omentin. Omentin levels were lower in stage 2 and 3 CKD but not
      stage 4 CKD patients compared to control. CONCLUSIONS: The results of the present
      study suggest that diabetes mellitus and inflammation should be associated with
      lower omentin levels in CKD population; however, this reduction resolves due to
      the failure of degradation and excretion of omentin when creatinine clearance
      falls below 30 ml/min (stage 4 CKD).

PMID- 24918535
TI  - Genetic variability of GCKR alters lipid profiles in children with monogenic and
      autoimmune diabetes.
AB  - PURPOSE: Mutations in the glucokinase (GCK) gene are associated with altered
      blood glucose and lipid concentrations. Our aim was to assess the effects on
      HbA1c and serum lipid levels of single nucleotide polymorphisms (SNPs) in 2 genes
      encoding proteins that interact with glucokinase: glucose-6-phospatase catalytic
      subunit 2 (G6PC2) and glucokinase regulatory protein (GCKR). METHODS: The study
      group included 129 children with GCK-MODY from the Polish Registry of Monogenic
      Diabetes and 395 with type 1 diabetes (T1DM), in whom we genotyped 2 SNPs in
      G6PC2 (rs560887) and GCKR (rs1260326). Lipid concentrations were assessed in
      fasting serum samples. RESULTS: Total and HDL cholesterol concentrations were
      significantly lower in the GCK-MODY group than in patients with T1DM (167.5+/
      32.5 mg/dl vs. 174.4+/-31.1 mg/dl, p=0.0435 and 48.42+/-14.3 mg/dl vs. 58.7+/
      12.7 mg/dl, p<0.0001, respectively). No differences in genotype distributions
      were found except for underrepresentation of GCKR TT homozygotes among GCK-MODY
      patients (10.9% in GCK-MODY vs. 17.7% in T1DM, p=0.0651). GCKR genotypes showed
      significant associations with lipid profiles and HbA1c levels, whereas no such
      associations were noted for G6PC2. After adjustment for confounders, TT
      homozygotes were shown to have higher total cholesterol and marginally higher LDL
      cholesterol and triglyceride levels (p=0.0245, p=0.0657 and p=0.0550,
      respectively). The difference between TT homozygotes and other genotypes was
      similar in magnitude within the GCK-MODY and T1DM groups. No significant
      interactions between the type of diabetes and the GCKR or G6PC2 genotype were
      detected. CONCLUSIONS: Individuals who are homozygous TT at rs1260326 of the GCKR
      gene have higher triglyceride, total and LDL cholesterol levels regardless of the
      presence of GCK mutations.

PMID- 24918536
TI  - Associations between bone, fat tissue and metabolic control in children and
      adolescents with type 1 diabetes mellitus.
AB  - AIMS: To investigate the relationship between bone-derived osteocalcin (OC),
      osteoprotegerin (OPG), Receptor Activator of Nuclear Factor NF-KB ligand (RANKL),
      and fat tissue-derived leptin and adiponectin with a clinical outcome of type 1
      diabetes mellitus (T1DM) in children and adolescents. METHODS: 78 patients (43
      girls and 35 boys), aged 11.5+/-4.3 years with T1DM and 11 age- and BMI-matched
      controls were included into the study. Patients were divided into 3 groups
      according to HbA1c level, I - below 7% [53 mmol/mol], II - 7-9% [53-75 mmol/mol]
      and III - above 9% [75 mmol/mol]. Blood samples for biochemical measurements were
      drawn at 8.00 AM, when the patients were in a fasting state. HbA1c was measured
      by the standardized IFCC method. OC, OPG, RANKL, leptin and adiponectin were
      measured by ELISA. ANOVA, and multiple regression analysis were used for
      statistical analysis. RESULTS: Significant differences in leptin and osteocalcin
      levels between groups with different HbA1c values were observed (p=0.03, p=0.04).
      Multiple regression analysis adjusted for age showed that serum OC and leptin
      negatively correlated with HbA1c levels (r=-0.22, p=0.004 and r=-0.27, p=0.0001,
      respectively). In contrast, serum OPG correlated positively with HbA1c (r=0.26,
      p=0.02) as well as with adiponectin (r=0.26, p=0.02) and RANKL (r=0.27, p=0.02)
      levels. The correlation of OC with HbA1c was the strongest in group I - patients
      with good metabolic control of DM (r=-0.43, p=0.03). In that group, in multiple
      regression analysis adjusted for age and BMI leptin correlated positively with
      daily dose of insulin (r=0.52, r=0.009). In group II and III in multiple
      regression analysis adjusted for age and BMI OC correlated negatively with leptin
      (r=-0.37, p=0.01). CONCLUSIONS: Our data suggest significant relationships
      between bone, fat tissue and glucose metabolism in pediatric patients with T1DM.
      The results can confirm that poor metabolic control is associated with reduced
      bone formation. On the other hand fat and bone tissue can influence glucose
      metabolism, potentiality in insulin-dependent manner. From these data leptin or
      OC may be potentially used as additional therapeutic agents for T1DM.

PMID- 24918537
TI  - Evaluation of styrene-divinylbenzene beads as a support to immobilize lipases.
AB  - A commercial and very hydrophobic styrene-divinylbenzene matrix, MCI GEL(r)
      CHP20P, has been compared to octyl-Sepharose(r) beads as support to immobilize
      three different enzymes: lipases from Thermomyces lanuginosus (TLL) and from
      Rhizomucor miehie (RML) and Lecitase(r) Ultra, a commercial artificial
      phospholipase. The immobilization mechanism on both supports was similar:
      interfacial activation of the enzymes versus the hydrophobic surface of the
      supports. Immobilization rate and loading capacity is much higher using MCI
      GEL(r) CHP20P compared to octyl-Sepharose(r) (87.2 mg protein/g of support using
      TLL, 310 mg/g using RML and 180 mg/g using Lecitase(r) Ultra). The thermal
      stability of all new preparations is much lower than that of the standard octyl
      Sepharose(r) immobilized preparations, while the opposite occurs when the
      inactivations were performed in the presence of organic co-solvents. Regarding
      the hydrolytic activities, the results were strongly dependent on the substrate
      and pH of measurement. Octyl-Sepharose(r) immobilized enzymes were more active
      versus p-NPB than the enzymes immobilized on MCI GEL(r) CHP20P, while RML became
      700-fold less active versus methyl phenylacetate. Thus, the immobilization of a
      lipase on this matrix needs to be empirically evaluated, since it may present
      very positive effects in some cases while in other cases it may have very
      negative ones. 

PMID- 24918538
TI  - Study on the synthesis, biological activity and spectroscopy of naphthalimide
      diamine conjugates.
AB  - Eleven novel naphthalimide-diamine conjugates were synthesized and their
      structures were confirmed by elemental analysis, 1H-NMR, 13C-NMR and MS. Their in
      vitro antitumor activities were assessed using MTT assays on two cancerous cell
      lines K562, HCT116, and one normal hepatoma cell line QSG 7701. Compound 7f
      exhibited potent antitumor activity on HCT116 cells and favorable cell
      selectivity toward QSG 7701 compared with the positive control, amonafide.
      Moreover, 7f could block HeG2 cells in the G2/M phase and induce HeG2 cells
      apoptosis. The interaction of compound 7f with herring sperm DNA was studied by
      UV/vis absorption and fluorescence spectroscopy under physiological conditions
      (pH = 7.4). The observed spectral quenching of compound 7f by DNA and the
      displacement of EB from DNA-EB complex by compound 7f indicated that compound 7f
      could intercalate into DNA base pairs, which was also corroborated by the effect
      of KI on compound-DNA interaction. Further caloric fluorescent tests revealed
      that the quenching mechanism was a static type. Meanwhile, the binding constants,
      thermodynamic parameters and the effect of NaCl on compound-DNA interaction
      showed that the type of interaction force was mainly hydrogen bonds and the
      binding process was driven by hydrogen and van der Waals bonding. 

PMID- 24918539
TI  - The edible brown seaweed Ecklonia cava reduces hypersensitivity in postoperative
      and neuropathic pain models in rats.
AB  - The current study was designed to investigate whether edible brown seaweed
      Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared
      nerve injury (SNI) rats. To evaluate pain-related behavior, we performed the
      mechanical withdrawal threshold (MWT) and thermal hypersensitivity tests measured
      by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior
      was also determined through analysis of ultrasonic vocalization. The results of
      experiments showed MWT values of the group that was treated with E. cava extracts
      by 300 mg/kg significantly increased; on the contrary, number of ultrasonic
      distress vocalization of the treated group was reduced at 6 h and 24 h after
      plantar incision operation (62.8%, p < 0.05). Moreover, E. cava 300 mg/kg treated
      group increased the paw withdrawal latency in hot-and cold-plate tests in the
      plantar incision rats. After 15 days of continuous treatment with E. cava
      extracts at 300 mg/kg, the treated group showed significantly alleviated SNI
      induced hypersensitivity response by MWT compared with the control group. In
      conclusion, these results suggest that E. cava extracts have potential analgesic
      effects in the case of postoperative pain and neuropathic pain in rats. 

PMID- 24918540
TI  - Antimicrobial activity of resveratrol analogues.
AB  - Stilbenes, especially resveratrol and its derivatives, have become famous for
      their positive effects on a wide range of medical disorders, as indicated by a
      huge number of published studies. A less investigated area of research is their
      antimicrobial properties. A series of 13 trans-resveratrol analogues was
      synthesized via Wittig or Heck reactions, and their antimicrobial activity
      assessed on two different grapevine pathogens responsible for severe diseases in
      the vineyard. The entire series, together with resveratrol, was first evaluated
      on the zoospore mobility and sporulation level of Plasmopara viticola (the
      oomycete responsible for downy mildew). Stilbenes displayed a spectrum of
      activity ranging from low to high. Six of them, including the most active ones,
      were subsequently tested on the development of Botrytis cinerea (fungus
      responsible for grey mold). The results obtained allowed us to identify the most
      active stilbenes against both grapevine pathogens, to compare the antimicrobial
      activity of the evaluated series of stilbenes, and to discuss the relationship
      between their chemical structure (number and position of methoxy and hydroxy
      groups) and antimicrobial activity. 

PMID- 24918541
TI  - Formylation of amines.
AB  - Methods to convert amines to formamides are of interest due to the many uses of
      formamides as synthetic intermediates. These methods include stoichiometric
      reactions of formylating reagents and catalytic reactions with CO as the carbonyl
      source. This review discusses the reported stoichiometric and catalytic
      approaches for preparation of formamides. 

PMID- 24918542
TI  - Methods of increasing the performance of radionuclide generators used in nuclear
      medicine: daughter nuclide build-up optimisation, elution-purification
      concentration integration, and effective control of radionuclidic purity.
AB  - Methods of increasing the performance of radionuclide generators used in nuclear
      medicine radiotherapy and SPECT/PET imaging were developed and detailed for
      99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation
      methods of the daughter nuclide build-up versus stand-by time and/or specific
      activity using mean progress functions were developed for increasing the
      performance of radionuclide generators. As a result of this optimisation, the
      separation of the daughter nuclide from its parent one should be performed at a
      defined optimal time to avoid the deterioration in specific activity of the
      daughter nuclide and wasting stand-by time of the generator, while the daughter
      nuclide yield is maintained to a reasonably high extent. A new characteristic
      parameter of the formation-decay kinetics of parent/daughter nuclide system was
      found and effectively used in the practice of the generator production and
      utilisation. A method of "early elution schedule" was also developed for
      increasing the daughter nuclide production yield and specific radioactivity, thus
      saving the cost of the generator and improving the quality of the daughter
      radionuclide solution. These newly developed optimisation methods in combination
      with an integrated elution-purification-concentration system of radionuclide
      generators recently developed is the most suitable way to operate the generator
      effectively on the basis of economic use and improvement of purposely suitable
      quality and specific activity of the produced daughter radionuclides. All these
      features benefit the economic use of the generator, the improved quality of
      labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a
      new method of quality control protocol set-up for post-delivery test of
      radionuclidic purity has been developed based on the relationship between gamma
      ray spectrometric detection limit, required limit of impure radionuclide activity
      and its measurement certainty with respect to optimising decay/measurement time
      and product sample activity used for QC quality control. The optimisation ensures
      a certainty of measurement of the specific impure radionuclide and avoids wasting
      the useful amount of valuable purified/concentrated daughter nuclide product.
      This process is important for the spectrometric measurement of very low activity
      of impure radionuclide contamination in the radioisotope products of much higher
      activity used in medical imaging and targeted radiotherapy. 

PMID- 24918543
TI  - Salidroside protects Caenorhabditis elegans neurons from polyglutamine-mediated
      toxicity by reducing oxidative stress.
AB  - Polyglutamine (polyQ) aggregation plays a pivotal role in the pathological
      process of Huntington's disease and other polyQ disorders. Therefore, strategies
      aiming at restoring dysfunction and reducing stresses mediated by polyQ toxicity
      are of therapeutic interest for proteotoxicity diseases. Salidroside, a glycoside
      from Rhodiola rosea, has been shown to have a variety of bioactivities, including
      antioxidant activity. Using transgenic Caenorhabditis elegans models, we show
      here that salidroside is able to reduce neuronal death and behavioral dysfunction
      mediated by polyQ expressed in ASH neurons, but the neuroprotective effect is not
      associated with prevention of polyQ aggregation per se. Further experiments
      reveal that the neuroprotective effect of salidroside in C. elegans models
      involves its antioxidant capabilities, including decrease of ROS levels and
      paraquat-induced mortality, increase of antioxidant enzyme activities and
      reduction of lipid peroxidation. These results demonstrate that salidroside
      exerts its neuroprotective function against polyQ toxicity via oxidative stress
      pathways. 

PMID- 24918544
TI  - Selective substitution of 31/42-OH in rapamycin guided by an in situ IR
      technique.
AB  - An in situ IR technique was applied in the selective synthesis of the key
      intermediate for rapamycin derivatives, which made the reaction endpoint easily
      defined. This technology solved a bothersome problem in the preparation of
      rapamycin derivatives, and based on this technique, the 31-OH and 42-OH of
      rapamycin were chemically modified by a series of quaternary ammonium salts to
      generate 11 compounds. The solubility of all these compounds was remarkably
      improved (25,000 times higher than that of rapamycin) and their structures were
      confirmed by MS, IR, 1D and 2D NMR techniques. 

PMID- 24918545
TI  - Physicochemically and pharmacokinetically stable nonapeptide KISS1 receptor
      agonists with highly potent testosterone-suppressive activity.
AB  - Modifications of metastin(45-54) produced peptide analogues with higher metabolic
      stability than metastin(45-54). N-terminally truncated nonapeptide 4 ([D-Tyr46,D
      Pya(4)47,azaGly51,Arg(Me)53]metastin(46-54)) is a representative compound with
      both potent agonistic activity and metabolic stability. Although 4 had more
      potent testosterone-suppressant activity than metastin, it possessed
      physicochemical instability at pH 7 and insufficient in vivo activity.
      Instability at pH 7 was dependent upon Asn48 and Ser49; substitution of Ser49
      with Thr49 reduced this instability and maintained KISS1 receptor agonistic
      activity. Furthermore, [D-Tyr46,D
      Trp47,Thr49,azaGly51,Arg(Me)53,Trp54]metastin(46-54) (14) showed 2-fold greater
      [Ca2+]i-mobilizing activity than metastin(45-54) and an apparent increase in
      physicochemical stability. N-terminal acetylation of 14 resulted in the most
      potent analogue, 22 (Ac-[D-Tyr46,D
      Trp47,Thr49,azaGly51,Arg(Me)53,Trp54]metastin(46-54)). With continuous
      administration, 22 possessed 10-50-fold more potent testosterone-suppressive
      activity in rats than 4. These results suggested that a controlled release of
      short-length KISS1 receptor agonists can suppress the hypothalamic-pituitary
      gonadal axis and reduce testosterone levels. Compound 22 was selected for further
      preclinical evaluation for hormone-dependent diseases.

PMID- 24918546
TI  - Congenital dacryocele with large intranasal cyst: efficacy of cruciate
      marsupialization, adjunctive procedures, and outcomes.
AB  - PURPOSE: To evaluate the safety and efficacy of a new technique of medial wall
      cruciate marsupialization of large intranasal cysts associated with dacryocele
      and to evaluate the outcomes. METHODS: A prospective, interventional consecutive
      case series of 7 patients with large intranasal cysts were included in this
      study. All patients underwent endoscopic marsupialization by a single surgeon
      (MJA) using a new technique involving a medial wall cruciate incision. Patients
      were followed up for a minimum of 6 months and analyzed for the resolution of
      dacryocele and intranasal cysts and anatomical and functional success. RESULTS:
      The mean age at presentation was 5.9 weeks with a female preponderance (71.4%).
      All patients presented with a subcutaneous swelling in lacrimal sac region. Acute
      dacryocystitis was noted in 42.8% (3/7). Associated lacrimal anomalies were noted
      in 28.5% (2/7), and associated respiratory distress was noted in 57.1% (4/7) of
      the patients. At a mean follow up of 10.8 months, anatomical patency and
      resolution of intranasal cyst were achieved in all cases, and functional success
      was noted in all except 1 patient. CONCLUSIONS: Endoscopic evaluation of all
      dacryoceles is recommended. Medial wall cruciate marsupialization is a safe and
      effective modality in the management of large intranasal cysts. Early diagnosis
      and appropriate quick referral are likely to prevent acute dacryocystitis,
      progression of dacryocele, and may aid in better outcomes.

PMID- 24918547
TI  - Assessing subunit dependency of the Plasmodium proteasome using small molecule
      inhibitors and active site probes.
AB  - The ubiquitin-proteasome system (UPS) is a potential pathway for therapeutic
      intervention for pathogens such as Plasmodium, the causative agent of malaria.
      However, due to the essential nature of this proteolytic pathway, proteasome
      inhibitors must avoid inhibition of the host enzyme complex to prevent toxic side
      effects. The Plasmodium proteasome is poorly characterized, making rational
      design of inhibitors that induce selective parasite killing difficult. In this
      study, we developed a chemical probe that labels all catalytic sites of the
      Plasmodium proteasome. Using this probe, we identified several subunit selective
      small molecule inhibitors of the parasite enzyme complex. Treatment with an
      inhibitor that is specific for the beta5 subunit during blood stage schizogony
      led to a dramatic decrease in parasite replication while short-term inhibition of
      the beta2 subunit did not affect viability. Interestingly, coinhibition of both
      the beta2 and beta5 catalytic subunits resulted in enhanced parasite killing at
      all stages of the blood stage life cycle and reduced parasite levels in vivo to
      barely detectable levels. Parasite killing was achieved with overall low host
      toxicity, something that has not been possible with existing proteasome
      inhibitors. Our results highlight differences in the subunit dependency of the
      parasite and human proteasome, thus providing a strategy for development of
      potent antimalarial drugs with overall low host toxicity. 

PMID- 24918548
TI  - Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine
      kinase.
AB  - Janus kinase-2 (JAK2) mediates signaling by various cytokines, including
      erythropoietin and growth hormone. JAK2 possesses tandem pseudokinase and
      tyrosine-kinase domains. Mutations in the pseudokinase domain are causally linked
      to myeloproliferative neoplasms (MPNs) in humans. The structure of the JAK2
      tandem kinase domains is unknown, and therefore the molecular bases for
      pseudokinase-mediated autoinhibition and pathogenic activation remain obscure.
      Using molecular dynamics simulations of protein-protein docking, we produced a
      structural model for the autoinhibitory interaction between the JAK2 pseudokinase
      and kinase domains. A striking feature of our model, which is supported by
      mutagenesis experiments, is that nearly all of the disease mutations map to the
      domain interface. The simulations indicate that the kinase domain is stabilized
      in an inactive state by the pseudokinase domain, and they offer a molecular
      rationale for the hyperactivity of V617F, the predominant JAK2 MPN mutation. 

PMID- 24918549
TI  - Treatment of gonococcal infection: when one drug is not enough.

PMID- 24918551
TI  - The changing face of challenges in the management of acne and rosacea.

PMID- 24918550
TI  - dbCerEx: a web-based database for the analysis of cervical cancer transcriptomes.
AB  - BACKGROUND: Cervical cancers are ranked the second-most hazardous ailments among
      women worldwide. In the past two decades, microarray technologies have been
      applied to study genes involved in malignancy progress. However, in most of the
      published microarray studies, only a few genes were reported leaving rather a
      large amount of data unused. Also, RNA-Seq data has become more standard for
      transcriptome analysis and is widely applied in cancer studies. There is a
      growing demand for a tool to help the experimental researchers who are keen to
      explore cervical cancer gene therapy, but lack computer expertise to access and
      analyze the high throughput gene expression data. DESCRIPTION: The dbCerEx
      database is designed to retrieve and process gene expression data from cervical
      cancer samples. It includes the genome wide expression profiles of cervical
      cancer samples, as well as a web utility to cluster genes with similar expression
      patterns. This feature will help researchers conduct further research to uncover
      novel gene functions. CONCLUSION: The dbCerEx database is freely available for
      non-commercial use at http://128.135.207.10/dbCerEx/, and will be updated and
      integrated with more features as needed.

PMID- 24918552
TI  - Therapeutic update on acne scarring.

PMID- 24918553
TI  - The duration of acne treatment.
AB  - BACKGROUND: Acne has a ~90% lifetime prevalence, however the duration of the
      condition and its treatment is not well characterized. The purpose of this study
      was to estimate for how long acne patients are treated. METHODS: Electronic
      patient records from an academic practice were queried to identify dermatology
      visits with an acne diagnosis (ICD-9: 706.1) between January 1, 2009 and June 1,
      2012. The duration of care for acne treatment was calculated as the time between
      the earliest and latest visits. Kaplan Meier analyses were used to describe
      treatment duration RESULTS: 1,130 patients had at least one visit acne-related
      visit to a dermatologist, with 631 (56%) having only one visit and 499 (44%)
      having multiple visits over the study period. For patients with multiple visits,
      the mean duration from first to last visit was 0.57 year (95% CI: 0.52, 0.62);
      25% ceased visiting in 0.25 year, 50% in 0.40 year, and 75% in 0.64 year.
      CONCLUSION: Our study provides a lower limit on the duration of acne treatment.
      The duration of acne treatment is longer than the duration of typical acne
      clinical trials. Understanding the duration of the disease can help set patients'
      treatment expectations, which may help improve adherence.

PMID- 24918554
TI  - Tolerability of topical antimicrobials in treatment of acne vulgaris.
AB  - BACKGROUND: Thirty to 40% of patients using topical treatments do not comply with
      their treatment regimen. OBJECTIVE: To examine how tolerability is assessed,
      tolerability ratings, and clinical significance of tolerability ratings of
      topical antimicrobials for acne. METHODS: A literature search was performed using
      the terms "tolerability AND acne AND (benzoyl peroxide OR antimicrobial OR
      clindamycin OR erythromycin OR dapsone OR sulfur OR sulfacetamide)." Inclusion
      criteria were: 1) evaluation of tolerability, 2) use of an identified topical
      antimicrobial for acne treatment without combination retinoid use, 3) an original
      study, in English. RESULTS: Thirty-four of 132 articles met the inclusion
      criteria. Tolerability was measured through subject and investigator assessment
      of specific tolerability parameters and by reporting of adverse events. Nearly
      all of the acne treatments were well tolerated. Treatment related study
      discontinuation rates were low and had little to no relation to the degree of
      tolerability measures. LIMITATIONS: Patients may be more adherent in clinical
      trials than in clinical practice. Differences in the measure used to assess
      tolerability make comparisons difficult. CONCLUSIONS: Topical antimicrobial acne
      therapy is generally well tolerated. Discontinuation rates are low under study
      conditions. Tolerability of topical antimicrobial therapy for acne may not have
      great clinical significance.

PMID- 24918555
TI  - Results of a Phase III, double-blind, randomized, parallel-group, non-inferiority
      study evaluating the safety and efficacy of isotretinoin-Lidose in patients with
      severe recalcitrant nodular acne.
AB  - BACKGROUND: Isotretinoin-Lidose, the first new formulation of isotretinoin in 30
      years, differs from previously approved isotretinoin formulations in that it is
      less dependent on the presence of fat in the gut for absorption. OBJECTIVE:
      Evaluate the safety profiles of isotretinoin-Lidose and food-dependent generic
      isotretinoin in the largest clinical study with isotretinoin-925 randomized
      patients from 49 study sites. Determine if the efficacy of this new formulation
      is noninferior to an existing isotretinoin. METHODS: Multicenter, double-blind,
      randomized, parallel-group, noninferiority trial. Study medication was taken with
      meals twice daily for 20 weeks. Patients were followed for 4 weeks after the last
      dose. Safety evaluations included recordings of adverse events, assessments for
      depression, anxiety, emergent psychotic symptoms, and suicidal ideation/behavior,
      as well as DEXA and X-ray evaluations and changes in bone age. Two co-primary
      efficacy outcomes were measured to assess noninferiority: a) change in total
      nodular facial and truncal lesion count at from baseline to week 20 and b)
      percentage of patients who experienced at least 90% reduction in nodular facial
      and truncal lesion count from baseline to week 20. LIMITATIONS: Although
      isotretinoin-Lidose can be taken without meals, it was given with food because
      the absorption of both formulations in the study had to be similar to detect
      noninferiority. RESULTS: The safety profile of the 2 formulations was comparable.
      Criteria for noninferiority for both co-primary efficacy outcomes were met based
      on predetermined margins. CONCLUSION: Safety and efficacy of isotretinoin-Lidose
      is similar and noninferior to food-dependent generic isotretinoin, respectively.

PMID- 24918556
TI  - Safety and efficacy comparison of minocycline microgranules vs lymecycline in the
      treatment of mild to moderate acne: randomized, evaluator-blinded, parallel, and
      prospective clinical trial for 8 weeks.
AB  - BACKGROUND: Minocycline and lymecycline are used in the treatment of acne, but
      there is not enough evidence to support superior efficacy of one of them.
      METHODS: 170 participants from 14 to 34 years old with mild to moderate facial
      acne vulgaris were recruited. 84 had 100 mg of minocycline in a single daily dose
      for 8 weeks and 86 had 300 mg of lymecycline in a single daily dose for 8 weeks.
      Participants were evaluated at baseline, week 4 and week 8. RESULTS: 65
      minocycline and 60 lymecycline patients were evaluable. The last observation
      carried forward for the count of non-inflammatory lesions changed from 37.5 +/-
      17.8 to 37.7 +/- 17.8 in the minocycline group and from 36.9 +/- 15.5 to 33.4 +/-
      19.3 in the lymecycline group (no significant changes); corresponding changes in
      inflammatory lesions were from 19.4 +/- 12.4 to 12.2 +/- 10.0 in the minocycline
      group and from 20.1 +/- 11.3 to 12.6 +/- 8.4 in lymecycline group (P< 0.05
      comparing baseline vs. final in both groups). Porphyrin counts varied from 899.5
      +/- 613.9 to 233.5 +/- 219.5 in the minocycline group and from 956.9 +/- 661.8 to
      411.8 +/- 411.5 in the lymecycline group (P<0.05 between the groups at study
      end). 36 (42.9%) patients receiving minocycline suffered 55 adverse events (22 of
      them gastrointestinal), while 28 (33.3%) lymecycline patients had 37 adverse
      events (15 of them gastrointestinal). One patient in the lymecycline group
      withdrew the study due to gastritis, and one more patient in the same group
      experienced eosinophilia. CONCLUSIONS: There were no differences between the
      groups in non-inflammatory and inflammatory lesion counts, and in the safety
      profile. Treatment with minocycline induced statistically significant decrease in
      facial porphyrin counts compared to the group treated with lymecycline
      (ClinicalTrials.gov number, NCT00988026).

PMID- 24918557
TI  - Rapid treatment of mild acne with a novel skin care system containing 1%
      salicylic acid, 10% buffered glycolic acid, and botanical ingredients.
AB  - The biggest hurdle in the treatment of acne vulgaris is patient non-compliance
      that is due in large part to poor tolerability to common acne medications. As
      such, new acne treatments must be developed that balance good anti-acne efficacy
      with excellent tolerability in order to ensure patient adherence and by extension
      ensure good clinical outcomes. The goal of the present study was to determine the
      tolerability and efficacy of a novel skin care system, composed of a cleanser,
      containing 1% salicylic acid and botanical ingredients, and a treatment gel,
      containing 1% salicylic acid, 10% buffered glycolic acid and botanical
      ingredients for the treatment of mild acne. In this single-center, open-label
      clinical study, 25 male and female volunteers used the test cleanser and test gel
      twice daily over six weeks. Tolerability assessments showed that the skin care
      regimen was very well tolerated by all study volunteers. Acne severity was
      significantly reduced by two acne grades at six weeks. Inflammatory lesion counts
      were significantly reduced, on average, by 59.06% (P <= 0.0001), 91.62% (P <=
      0.0001), 90.85% (P <= 0.0001) and by 98.55% (P <= 0.0001) at weeks 1, 2, 4, and
      6, respectively. Non-inflammatory lesion counts were reduced, on average, by
      13.54% (ns), 38.95% (P <= 0.0001), 44.48% (P <= 0.0001), and by 56.10% (P <=
      0.0001) at weeks 1, 2, 4, and 6, respectively. Standardized photography also
      demonstrated a progressive reduction in acne lesions over time. In conclusion,
      results of the present study suggest that the tested skin care regimen offers
      rapid acne clearance and excellent tolerability that together may help to improve
      patient adherence as well as treatment outcome.

PMID- 24918558
TI  - Randomized, phase 2, dose-ranging study in the treatment of rosacea with
      encapsulated benzoyl peroxide gel.
AB  - OBJECTIVE: Compare the safety and efficacy of 1% and 5% silica encapsulated
      benzoyl peroxide (E-BPO) in patients with papulopustular rosacea. DESIGN: Multi
      centered randomized, double blind, vehicle controlled parallel group, 12 week
      treatment in 92 patients with papulopustular rosacea. Primary endpoints were
      dichotomized IGA with success defined as clear/near clear and reduction in
      inflammatory lesions. PATIENTS: 92 patients: 74% graded as moderate IGA, 14%
      severe and 12% mild. The mean inflammatory lesion count was 24. INTERVENTION:
      Once daily treatment for 12 weeks with vehicle, 1% or 5% E-BPO. RESULTS: 1% and
      5% E-BPO were superior to vehicle in reducing papulopustular lesions P =0.01 and
      P =0.02. 5% E-BPO was superior to vehicle for IGA P =0.0013.

PMID- 24918559
TI  - The quality of life impact of acne and rosacea compared to other major medical
      conditions.
AB  - BACKGROUND: Acne and rosacea cause significant negative impact on quality of
      life. There is limited information comparing the health-related quality of life
      (HRQL) impact associated with acne and rosacea to other patient populations.
      PURPOSE: We review available literature to assess the HRQL impact of acne and
      rosacea and compare them with major medical conditions. METHODS: A PubMed search
      identified studies that utilized the Short Form 36 (SF-36), the Dermatology Life
      Quality Index (DLQI), and the willingness-to-pay (WTP) metric to assess the HRQL
      impact of acne and rosacea. These data were compared to HRQL values for other
      diseases. RESULTS: The HRQL impact of acne is similar to asthma, epilepsy,
      diabetes, back pain, arthritis, and coronary heart disease using SF-36 data. DLQI
      scores for acne ranged from 2 to 17.7 and for rosacea ranged from 4.3 to 17.3;
      the DLQI scores for psoriasis ranged from 1.7 to 18.2. WTP data identified ranged
      widely for both acne and rosacea. LIMITATIONS: There was limited broadly
      generalizable data for acne and rosacea. CONCLUSIONS: Acne and rosacea impact
      HRQL to a similar degree as other major medical conditions by indirect comparison
      to psoriasis, a skin condition causing significant disability, and by direct
      comparison for acne. In the setting of limited health care resources, allocation
      should be grounded in the evidence that acne and rosacea are not trivial in their
      effects.

PMID- 24918561
TI  - Cutaneous tolerability to tretinoin shows little variation with Fitzpatrick skin
      type.
AB  - Determinants of skin irritability are poorly understood. This study aims to
      assess differences in cutaneous safety/irritation based on Fitzpatrick skin type
      among patients with acne treated with tretinoin gel microsphere (TGM). This was a
      phase 4, 12-week, prospective, nonrandomized, open-label, multicenter study.
      Approximately 500 patients with mild to moderate acne were treated with TGM 0.04%
      or 0.1% and assessed for cutaneous irritation at baseline and weeks 3, 6, and 12.
      In this post hoc analysis of patients with Fitzpatrick skin type I-III vs
      Fitzpatrick skin type IV-VI, there was a general trend toward initial worsening
      of cutaneous adverse events (AEs) by week 3 across all variables and groups. This
      was followed by a trend toward improvement and resolution of skin-related AEs
      from week 3 to week 12 regardless of Fitzpatrick skin type, with a few
      exceptions. Erythema was the only cutaneous AE that consistently decreased among
      patients with darker skin. Results from a subsequent 3-group analysis
      (Fitzpatrick I-II vs Fitzpatrick III-IV vs Fitzpatrick V-VI) generally mirrored
      those from the 2-group study. Study limitations include patient nonadherence,
      lack of a placebo arm, and lack of data regarding the impact of concurrent
      medications on outcomes. There was no correlation between irritation and
      Fitzpatrick skin type. ABBREVIATIONS USED: adverse event (AE), analysis of
      variance (ANOVA), benzoyl peroxide (BP), case report form (CRF), modified Global
      Acne Grading Score (mGAGS), tretinoin gel microsphere (TGM).

PMID- 24918560
TI  - Improvement in facial erythema within 30 minutes of initial application of
      brimonidine tartrate in patients with rosacea.
AB  - BACKGROUND: Brimonidine tartrate (BT) 0.5% gel demonstrated significantly greater
      efficacy versus vehicle gel once-daily for the treatment of moderate to severe
      erythema of rosacea. OBJECTIVES: To assess the 30-minute speed of onset of
      topical BT 0.5% gel in reducing facial erythema in Phase III studies as measured
      by subject and clinician assessments of erythema. METHODS: Two Phase III,
      randomized, controlled studies with identical design in which subjects with
      moderate erythema of rosacea (study A: n=260; study B: n=293) were randomized 1:1
      to apply topical BT 0.5% or vehicle gel once-daily for 4 weeks. Evaluations
      included severity of erythema based on Clinician's Erythema Assessment (CEA) and
      Patient's Self-Assessment (PSA) prior to study drug application and at 30 minutes
      after application on days 1, 15, and 29. RESULTS: 97.7% and 96.6% of subjects
      reported normal study completion for studies A and B, respectively. The
      percentage of subjects achieving a 1-grade improvement in both CEA and PSA was
      significantly increased at 30 minutes post-dosing with BT 0.5% gel compared to
      vehicle gel on visit days (day 1: 27.9 vs 6.9%, P <0.001; day 15: 55.9 vs 21.1%,
      P <0.001; Day 29: 58.3 vs 32.0%, P <0.001 for BT 0.5% gel vs vehicle) in study A.
      Similar results were shown for study B. CONCLUSIONS: Once-daily topical BT gel
      0.5% is not only efficacious at reducing facial erythema but also exhibits
      response within 30 minutes of application in a significant number of patients
      throughout both Phase III studies.

PMID- 24918562
TI  - A retrospective analysis of 72 patients on prior efalizumab subsequent to the
      time of voluntary market withdrawal in 2009.
AB  - BACKGROUND: Efalizumab was voluntarily withdrawn from the market in April 2009
      after four cases of progressive multifocal leukoencephalopathy. OBJECTIVE: To
      review the baseline characteristics and psoriasis phenotypes of patients with
      prior excelled response to efalizumab, and to determine the response of these
      patients to prior as well as subsequent therapies. By defining this subgroup of
      patients, particularly relating to palmoplantar psoriasis, future therapeutic
      considerations could be improved. DESIGN: A retrospective review of 72 patients
      who were on efalizumab at the time of market withdrawal was conducted. Data was
      obtained through chart review of patients at a specialty psoriasis clinic in
      Dallas, TX. MAIN OUTCOMES AND MEASURES: Patient characteristics, details of
      efalizumab use, and efficacy of efalizumab compared with other psoriasis
      treatment modalities. RESULTS: Of the 72 patients, 24 (33%) were found to have
      palmoplantar disease. As a group, these patients were older, more likely to be
      female, and less likely to have a family history of psoriasis. 48 patients (67%)
      were on one or more systemic and/or biologic medication prior to starting
      efalizumab. Their BSA improved from 5.45 to 0.8 as a group. Six patients were
      identified as having failed TNF alpha antagonist treatment prior to starting
      efalizumab. All responded well to the medication with an average BSA of 0.54.
      Five of these six patients had evidence of palmoplantar disease prior to starting
      efalizumab and five of these six patients were female. Eleven patients (15%)
      experienced neurologic side effects and 13 (18%) had infections while on
      efalizumab treatment. LIMITATIONS: This was a retrospective review. Quality of
      life issues could not always be fully assessed from the data available.
      CONCLUSIONS AND RELEVANCE: Efalizumab was effectively utilized in our clinical
      practice to treat patients with palmoplantar psoriasis, including six patients
      who had failed prior treatment with one or more TNF alpha antagonist agents.

PMID- 24918563
TI  - Only skin deep: optimism and public self-consciousness did not associate with the
      placebo response in a dermatology clinical trial.
AB  - OBJECTIVE: Although not well-understood, dermatologic diseases studied in
      clinical trials often demonstrate substantial response to placebo. The study
      objective is to determine if optimism, public self-consciousness and other
      personality traits predict response to placebo or active treatment in a
      dermatology clinical trial. METHODS: A questionnaire was mailed to subjects
      previously enrolled in a two-center rosacea study who had been randomized to
      either a treatment or placebo gel. The questionnaire included the Revised Life
      Orientation Test (LOT-R), the Public Self-Consciousness Scale, and questions to
      assess personality traits. RESULTS: Forty-seven subjects out of 83 (57%) returned
      the questionnaire. There was no statistically significant difference in the LOT-R
      score in those who responded to placebo versus those who did not (18.08 vs 17.92,
      P =0.92) nor in those who responded to active treatment versus those who did not
      (16.27 vs 15.86, P =0.79). There was no statistically sigificant difference in
      public-self consciousness among placebo or active treatment responders versus non
      responders (11.75 vs 10.67, P =0.66; 13.55 vs 14.45, P =0.68). The placebo
      responders were more likely to report that they were not unusually sensitive to
      most drugs/medications (X2= 8.33, P =0.004). CONCLUSION: Although this pilot
      study is small, there was no meaningful difference in levels of optimism or
      public self-consciousness among those who responded to placebo. Placebo
      responders were more likely to report that they were not sensitive to most
      drugs/medications, raising the possibility that they are actually less likely to
      detect when they are on medications.

PMID- 24918564
TI  - The effect of desonide hydrogel on pruritis associated with atopic dermatitis.
AB  - Itch is a common and troubling symptom of atopic dermatitis. It is not mediated
      by histamine, and standard anti-itch therapies, therefore, have limited benefit
      for most AD patients. Instead, anti-inflammatory agents are used to reduce
      inflammation and therefore improve associated itch. Studies confirm that long
      term use of corticosteroids can lead to a reduction in pruritus. A pilot study
      was designed to assess the effects of one week of twice-daily application of
      desonide hydrogel 0.05% for the treatment of atopic dermatitis. Active treatment
      was associated with significant improvements in IGA scores at day 3 and day 7
      (mean score 0.55, 75.83% improvement from Baseline; P <.0001) and pruritus VAS
      scores at day 3 and day 7 (mean 6.35-point, 86.61% reduction in VAS scores; P
      <.0001). Treatment with the convenient, hydrating hydrogel formulation is
      effective and associated with an improvement in subjects' quality of life.

PMID- 24918565
TI  - Systematic review of vismodegib toxicity profile in the treatment of advanced
      basal cell carcinomas compared to other systemic therapies in dermatology.
AB  - Vismodegib is a first-in-class, hedgehog-signal inhibitor that is FDA-approved
      for use with advanced basal cell carcinomas (BCCs) that cannot be removed by
      either surgical resection or treated with radiation. Release of the drug was fast
      tracked because of need for this type of drug, and its overall efficacy in
      clinical trial by producing either regression or even resolution of advanced
      BCCs. Compared to placebo, patients using vismodegib have arrested BCC
      progression, reduced size of BCC, and decreased recurrence of BCC. Unfortunately,
      vismodegib has notable adverse effects (especially those of alopecia,
      gastrointestinal, muscle spasms, and dysguesia) that make dermatologists
      reluctant to prescribe the drug and patients unwilling to undergo therapy. In
      this article, we tackle this dilemma by comparing the toxicity profile of
      vismodegib to the adverse effect profiles of other dermatologic
      chemotherapeutics, immunomodulators, retinoids, and biologics. Considering that
      many of these drugs carry their own risks and those drugs used to treat advanced
      melanoma have similar toxicity profiles to that of vismodegib, we hope
      dermatologists and patients alike will be more willing to try vismodegib as a
      treatment option for advanced BCCs in the future.

PMID- 24918566
TI  - Incorrect reconstitution of incobotulinumtoxinA leads to loss of neurotoxin.
AB  - BACKGROUND: IncobotulinumtoxinA (INCO) was approved for aesthetic use in the
      United States in 2011. When reconstituted per manufacturer's instructions,
      diminished delivery of INCO in US may result. OBJECTIVE: Investigators sought to
      determine whether potential loss of decreased motor activity could be
      demonstrated, using a simple reconstitution technique. METHODS AND MATERIALS: In
      this 5-patient study, investigators added 2.0 mL of saline to INCO powder at the
      bottom of the first of 5 vials, swirling gently to dissolve INCO powder at the
      bottom. Reconstituted INCO was discarded and the cap was replaced. The "empty"
      vial then received 0.6 mL of saline, and was swirled and inverted 3 times to
      ensure dissolution. The 0.6 mL from the first vial was added to the second
      "empty" vial and the process was repeated for the remaining 3 vials (5 vials per
      patient). Patients were injected from reconstitution of "empty" vials to
      determine neuromodulatory activity. Pre- and post-treatment patient photographs
      of maximal contraction were taken. RESULTS: Markedly diminished maximal frown
      could be observed in all 5 patients. CONCLUSION: Improper reconstitution of INCO,
      or swirling without inversion of the vial following saline injection, can result
      in significant loss of units of the neurotoxin in the clinical setting.

PMID- 24918567
TI  - Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic
      keratosis: 12-month results.
AB  - INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after
      cryosurgery are high, and this treatment does not address field cancerization. We
      investigated the efficacy and safety of field treatment of AKs with ingenol
      mebutate gel following cryosurgery. METHODS: In this phase 3, randomized, double
      blind, vehicle-controlled study (NCT01541553), patients >=18 years with four to
      eight clinically typical, visible, discrete AKs within a contiguous 25-cm2
      treatment area on the face or scalp underwent cryosurgery followed 3 weeks later
      by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days.
      Endpoints included complete clearance at week 11 and safety and efficacy over 12
      months. RESULTS: In 329 randomized patients, complete clearance rates were
      greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month
      12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new
      lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P =.02). At
      month 12, mean percentage reduction of AKs was higher with ingenol mebutate than
      with vehicle (68.2% vs 54.1%; P =.002). The probability of remaining free of
      lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78%
      vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively.
      Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events
      occurred; all adverse events resolved within 2 weeks of starting treatment.
      CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following
      cryosurgery significantly enhanced clearance of baseline lesions, and was well
      tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced
      development of new lesions in the treated field.

PMID- 24918568
TI  - Successful desensitization to brentuximab vedotin after hypersensitivity
      reaction.
AB  - Monoclonal antibodies (mAb) have become the standard of care for numerous
      diseases. However, side effects including infusion and hypersensitivity reactions
      experienced by patients continue to be a limiting factor in their use. In the
      therapy of cancer, treatment choices are frequently limited and minimizing side
      effects of a life-saving or life-prolonging therapy becomes of the utmost
      importance. We report the successful use of a rapid desensitization protocol in a
      patient with NHL, treated with a novel antibody-drug conjugate, chimeric
      monoclonal antibody linked to the antimitotic agent monomethyl auristatin E
      (MMAE) Brentuximab vedotin, who had previously developed a hypersensitivity
      reaction.

PMID- 24918569
TI  - Leuprolide acetate-induced generalized papular eruption.
AB  - Leuprolide acetate, a gonadotropin-releasing hormone agonist, is used in the
      treatment of prostate cancer. We report a unique case of a disseminated papular
      rash following leuprolide acetate injections in a 65-year-old man that shares
      clinical and histopathological features of papuloerythroderma of Ofuji.
      Leuprolide-induced papuloerythroderma, as well as a limited number of other
      disseminated cutaneous eruptions caused by this drug, is extremely rare, with
      only one case previously reported. Our case calls attention to this uncommon side
      effect in a commonly used hormonal therapy.

PMID- 24918570
TI  - Rosacea fulminans with extrafacial lesions in an elderly man: successful
      treatment with subantimicrobial-dose doxycycline.
AB  - Rosacea fulminans, previously known as pyoderma faciale, is a rare disease
      occurring almost exclusively in young women characterized by the sudden eruption
      of coalescing papules and pustules, and large cystic nodules limited to the face.
      Patients generally respond well to standard therapy consisting of systemic
      isotretinoin in combination with topical and systemic corticosteroids. Lesions
      usually resolve with minimal scarring with appropriate management. We describe an
      elderly male patient with extrafacial rosacea fulminans successfully treated with
      daily subantimicrobial (40mg) dose doxycycline (SDD). To our knowledge, this is
      the first report of rosacea fulminans with extrafacial lesions in an elderly
      male. We suggest that SDD may be a safe and effective alternative, particularly
      for those unable to tolerate standard therapy.

PMID- 24918571
TI  - Evolving concepts in the pathogenesis of acne vulgaris.

PMID- 24918572
TI  - Re-evaluating treatment targets in acne vulgaris: adapting to a new understanding
      of pathophysiology.
AB  - Two primary factors are changing current approaches to the management of acne
      vulgaris (AV): the continuously evolving role of Propionibacterium acnes in the
      pathophysiology of AV and recent evidence of an inflammatory basis for AV via
      innate immunity. The developing concepts emphasize that acne is primarily an
      inflammatory disease. The emerging concept of subclinical inflammation and its
      effect on development and progression of acne lesions correlating with the
      sequence of the underlying inflammation process has been a major change in our
      understanding of acne pathogenesis. Thus, inflammation has become the major
      feature of the disease process from onset to resolution, including
      postinflammatory erythema, postinflammatory hyperpigmentation, and scarring. Our
      treatment targets may also need to be reconsidered, with more emphasis on anti
      inflammatory treatments.

PMID- 24918573
TI  - Acne vulgaris in skin of color: understanding nuances and optimizing treatment
      outcomes.
AB  - According to the United States national survey data, acne vulgaris is the leading
      dermatologic diagnosis among African Americans, Hispanics/Latinos, and
      Asians/Pacific Islanders. This patient population, collectively referred to as
      having skin of color, exhibits clinical and therapeutic nuances that are relevant
      in the management of acne. Understanding the nuances in clinical presentation,
      safety considerations, cultural factors, and desired treatment endpoints is key
      to ensuring successful outcomes.

PMID- 24918574
TI  - Antibiotic resistance and acne: where we stand and what the future holds.
AB  - Antibiotic resistance is described as "a global public health challenge" and a
      "major health security challenge of the 21st century" by global health
      authorities,1 and there is a growing need for dermatologists to counteract it in
      their treatments of acne.3,4 Antibiotic limiting regimens, such as a combination
      of topical retinoids and benzoyl peroxide, have shown effectiveness in the
      treatment of acne; and topical probiotics could also play a needed role.

PMID- 24918575
TI  - Lipopolysaccharide induces immune activation and SIV replication in rhesus
      macaques of Chinese origin.
AB  - BACKGROUND: Chronic immune activation is a hallmark of progressive HIV infection
      and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial
      lipopolysaccharide (LPS) in the circulation has been implicated as a key factor
      in HIV infection-related systemic immune activation. We thus investigate the
      impact of LPS on systemic immune activation in simian immunodeficiency virus
      (SIV)-infected rhesus macaques of Chinese origin. METHODS: The animals were
      inoculated intravenously with SIVmac239. The levels of plasma viral load and host
      inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio
      and systemic immune activation markers were examined by flow cytometric analysis
      of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels
      were determined using biochemistry analyzer. The plasma levels of LPS were
      determined by Tachypleus Amebocyte Lysate (TAL) test. RESULTS: The animals
      inoculated with SIVmac239 became infected as evidenced by the increased plasma
      levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected
      animals induced a transient increase of plasma SIV RNA and immune activation,
      which was indicated by the elevated expression of the inflammatory cytokines and
      CD4+HLA-DR+ T cells in PBMCs. CONCLUSIONS: These data support the concept that
      LPS is a driving factor in systemic immune activation of HIV disease.

PMID- 24918576
TI  - Lithological control on phytolith carbon sequestration in moso bamboo forests.
AB  - Phytolith-occluded carbon (PhytOC) is a stable carbon (C) fraction that has
      effects on long-term global C balance. Here, we report the phytolith and PhytOC
      accumulation in moso bamboo leaves developed on four types of parent materials.
      The results show that PhytOC content of moso bamboo varies with parent material
      in the order of granodiorite (2.0 g kg(-1)) > granite (1.6 g kg(-1)) > basalt
      (1.3 g kg(-1)) > shale (0.7 g kg(-1)). PhytOC production flux of moso bamboo on
      four types of parent materials varies significantly from 1.0 to 64.8 kg CO2 ha(
      1) yr(-1), thus a net 4.7 * 10(6) -310.8 * 10(6) kg CO2 yr(-1) would be
      sequestered by moso bamboo phytoliths in China. The phytolith C sequestration
      rate in moso bamboo of China will continue to increase in the following decades
      due to nationwide bamboo afforestation/reforestation, demonstrating the potential
      of bamboo in regulating terrestrial C balance. Management practices such as
      afforestation of bamboo in granodiorite area and granodiorite powder amendment
      may further enhance phytolith C sequestration through bamboo plants.

PMID- 24918577
TI  - Chitinase-like (CTL) and cellulose synthase (CESA) gene expression in gelatinous
      type cellulosic walls of flax (Linum usitatissimum L.) bast fibers.
AB  - Plant chitinases (EC 3.2.1.14) and chitinase-like (CTL) proteins have diverse
      functions including cell wall biosynthesis and disease resistance. We analyzed
      the expression of 34 chitinase and chitinase-like genes of flax (collectively
      referred to as LusCTLs), belonging to glycoside hydrolase family 19 (GH19).
      Analysis of the transcript expression patterns of LusCTLs in the stem and other
      tissues identified three transcripts (LusCTL19, LusCTL20, LusCTL21) that were
      highly enriched in developing bast fibers, which form cellulose-rich gelatinous
      type cell walls. The same three genes had low relative expression in tissues with
      primary cell walls and in xylem, which forms a xylan type of secondary cell wall.
      Phylogenetic analysis of the LusCTLs identified a flax-specific sub-group that
      was not represented in any of other genomes queried. To provide further context
      for the gene expression analysis, we also conducted phylogenetic and expression
      analysis of the cellulose synthase (CESA) family genes of flax, and found that
      expression of secondary wall-type LusCESAs (LusCESA4, LusCESA7 and LusCESA8) was
      correlated with the expression of two LusCTLs (LusCTL1, LusCTL2) that were the
      most highly enriched in xylem. The expression of LusCTL19, LusCTL20, and LusCTL21
      was not correlated with that of any CESA subgroup. These results defined a
      distinct type of CTLs that may have novel functions specific to the development
      of the gelatinous (G-type) cellulosic walls. 

PMID- 24918578
TI  - Non-collinear magnetism induced by frustration in transition-metal nanostructures
      deposited on surfaces.
AB  - How does magnetism behave when the physical dimension is reduced to the size of
      nanostructures? The multiplicity of magnetic states in these systems can be very
      rich, in that their properties depend on the atomic species, the cluster size,
      shape and symmetry or choice of the substrate. Small variations of the cluster
      parameters may change the properties dramatically. Research in this field has
      gained much by the many novel experimental methods and techniques exhibiting
      atomic resolution. Here we review the ab-initio approach, focusing on recent
      calculations on magnetic frustration and occurrence of non-collinear magnetism in
      antiferromagnetic nanostructures deposited on surfaces. 

PMID- 24918579
TI  - Seasonal distribution and historic trends in abundance of white sharks,
      Carcharodon carcharias, in the western North Atlantic Ocean.
AB  - Despite recent advances in field research on white sharks (Carcharodon
      carcharias) in several regions around the world, opportunistic capture and
      sighting records remain the primary source of information on this species in the
      northwest Atlantic Ocean (NWA). Previous studies using limited datasets have
      suggested a precipitous decline in the abundance of white sharks from this
      region, but considerable uncertainty in these studies warrants additional
      investigation. This study builds upon previously published data combined with
      recent unpublished records and presents a synthesis of 649 confirmed white shark
      records from the NWA compiled over a 210-year period (1800-2010), resulting in
      the largest white shark dataset yet compiled from this region. These
      comprehensive records were used to update our understanding of their seasonal
      distribution, relative abundance trends, habitat use, and fisheries interactions.
      All life stages were present in continental shelf waters year-round, but median
      latitude of white shark occurrence varied seasonally. White sharks primarily
      occurred between Massachusetts and New Jersey during summer and off Florida
      during winter, with broad distribution along the coast during spring and fall.
      The majority of fishing gear interactions occurred with rod and reel, longline,
      and gillnet gears. Historic abundance trends from multiple sources support a
      significant decline in white shark abundance in the 1970s and 1980s, but there
      have been apparent increases in abundance since the 1990s when a variety of
      conservation measures were implemented. Though the white shark's inherent
      vulnerability to exploitation warrants continued protections, our results suggest
      a more optimistic outlook for the recovery of this iconic predator in the
      Atlantic. 

PMID- 24918580
TI  - Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet
      induced NAFLD mice.
AB  - Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and
      fruits, has been shown to have potent anti-oxidative and anti-obesity activity.
      However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly
      understood. In this study, we investigated the beneficial effects of GA
      administration on nutritional hepatosteatosis model by a more "holistic view"
      approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to
      obtain information that might lead to a better understanding of the mode of
      action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow
      diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and
      100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations
      indicated that the daily administration of GA protects against hepatic steatosis,
      obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD
      mice. In addition, partial least squares discriminant analysis scores plots
      demonstrated that the cluster of HFD fed mice is clearly separated from the
      normal group mice plots, indicating that the metabolic characteristics of these
      two groups are distinctively different. Specifically, the GA-treated mice are
      located closer to the normal group of mice, indicating that the HFD-induced
      disturbances to the metabolic profile were partially reversed by GA treatment.
      Our results show that the hepatoprotective effect of GA occurs in part through a
      reversing of the HFD caused disturbances to a range of metabolic pathways,
      including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis),
      amino acids metabolism, choline metabolism and gut-microbiota-associated
      metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics
      approach is a useful platform for natural product functional evaluation. The
      selected metabolites are potentially useful as preventive action biomarkers and
      could also be used to help our further understanding of the effect of GA in
      hepatosteatosis mice. 

PMID- 24918581
TI  - QKI impairs self-renewal and tumorigenicity of oral cancer cells via repression
      of SOX2.
AB  - Cancer stem cells (CSCs) may contribute to tumor initiation, distant metastasis
      and chemo-resistance. One of RNA-binding proteins, Quaking (QKI), was reported to
      be a tumor suppressor. Here we showed that reduced QKI levels were observed in
      many human oral cancer samples. Moreover further reduction of QKI expression in
      CSCs was detected compared with non-CSCs in oral cancer cell lines.
      Overexpressing QKI in oral cancer cells significantly reduced CSC sphere
      formation and stem cell-associated genes. In tumor implanting nude mice model,
      QKI significantly impeded tumor initiation rates, tumor sizes and lung metastasis
      rates. As a contrast, knocking down QKI enhanced the above effects. Among the
      putative CSC target genes, SOX2 expression was negatively affected by QKI,
      mechanism study revealed that QKI may directly regulate SOX2 expression via
      specific binding with its 3'UTR in a cis element-dependent way. Loss of SOX2 even
      completely reversed the sphere forming ability in QKI knockdown cell line. Taken
      together, these data demonstrated that SOX2 is an important CSC regulator in oral
      cancer. QKI is a novel CSC inhibitor and impaired multiple oral CSC properties
      via partial repression of SOX2. Therefore, reduced expression of QKI may provide
      a novel diagnostic marker for oral cancer. 

PMID- 24918582
TI  - Dense genotyping of immune-related loci identifies variants associated with
      clearance of HPV among HIV-positive women in the HIV epidemiology research study
      (HERS).
AB  - Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal
      factor of cervical cancer. Most women naturally clear HPV infections; however,
      the biological mechanisms related to HPV pathogenesis have not been clearly
      elucidated. Host genetic factors that specifically regulate immune response could
      play an important role. All HIV-positive women in the HIV Epidemiology Research
      Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit
      were included in the study. Cervicovaginal lavage samples were tested for HPV
      using type-specific HPV hybridization assays. Type-specific HPV clearance was
      defined as two consecutive HPV-negative tests after a positive test. DNA from
      participants was genotyped for 196,524 variants within 186 known immune related
      loci using the custom ImmunoChip microarray. To assess the influence of each
      single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional
      hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+
      count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three
      analytical models were performed: race-specific (African Americans (n = 258),
      European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis,
      and meta-analysis of pooled independent race-specific analyses. Women were
      followed for a median time of 1,617 days. Overall, three SNPs (rs1112085,
      rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the
      SMAD3 gene were associated with HR-HPV clearance (p<10(-6)). A variant
      (rs1633038) in HLA-G were also significantly associated in African American.
      Results from this study support associations of immune-related genes, having
      potential biological mechanism, with differential cervical HR-HPV infection
      outcomes.

PMID- 24918583
TI  - Integrated pathway clusters with coherent biological themes for target
      prioritisation.
AB  - Prioritising candidate genes for further experimental characterisation is an
      essential, yet challenging task in biomedical research. One way of achieving this
      goal is to identify specific biological themes that are enriched within the gene
      set of interest to obtain insights into the biological phenomena under study.
      Biological pathway data have been particularly useful in identifying functional
      associations of genes and/or gene sets. However, biological pathway information
      as compiled in varied repositories often differs in scope and content, preventing
      a more effective and comprehensive characterisation of gene sets. Here we
      describe a new approach to constructing biologically coherent gene sets from
      pathway data in major public repositories and employing them for functional
      analysis of large gene sets. We first revealed significant overlaps in gene
      content between different pathways and then defined a clustering method based on
      the shared gene content and the similarity of gene overlap patterns. We
      established the biological relevance of the constructed pathway clusters using
      independent quantitative measures and we finally demonstrated the effectiveness
      of the constructed pathway clusters in comparative functional enrichment analysis
      of gene sets associated with diverse human diseases gathered from the literature.
      The pathway clusters and gene mappings have been integrated into the TargetMine
      data warehouse and are likely to provide a concise, manageable and biologically
      relevant means of functional analysis of gene sets and to facilitate candidate
      gene prioritisation. 

PMID- 24918584
TI  - Reactive recruitment of attentional control in math anxiety: an ERP study of
      numeric conflict monitoring and adaptation.
AB  - This study uses event-related brain potentials (ERPs) to investigate the
      electrophysiological correlates of numeric conflict monitoring in math-anxious
      individuals, by analyzing whether math anxiety is related to abnormal processing
      in early conflict detection (as shown by the N450 component) and/or in a later,
      response-related stage of processing (as shown by the conflict sustained
      potential; Conflict-SP). Conflict adaptation effects were also studied by
      analyzing the effect of the previous trial's congruence in current interference.
      To this end, 17 low math-anxious (LMA) and 17 high math-anxious (HMA) individuals
      were presented with a numerical Stroop task. Groups were extreme in math anxiety
      but did not differ in trait or state anxiety or in simple math ability. The
      interference effect of the current trial (incongruent-congruent) and the
      interference effect preceded by congruence and by incongruity were analyzed both
      for behavioral measures and for ERPs. A greater interference effect was found for
      response times in the HMA group than in the LMA one. Regarding ERPs, the LMA
      group showed a greater N450 component for the interference effect preceded by
      congruence than when preceded by incongruity, while the HMA group showed greater
      Conflict-SP amplitude for the interference effect preceded by congruence than
      when preceded by incongruity. Our study showed that the electrophysiological
      correlates of numeric interference in HMA individuals comprise the absence of a
      conflict adaptation effect in the first stage of conflict processing (N450) and
      an abnormal subsequent up-regulation of cognitive control in order to overcome
      the conflict (Conflict-SP). More concretely, our study shows that math anxiety is
      related to a reactive and compensatory recruitment of control resources that is
      implemented only when previously exposed to a stimuli presenting conflicting
      information. 

PMID- 24918585
TI  - Increasing minimum daily temperatures are associated with enhanced pesticide use
      in cultivated soybean along a latitudinal gradient in the mid-western United
      States.
AB  - Assessments of climate change and food security often do not consider changes to
      crop production as a function of altered pest pressures. Evaluation of potential
      changes may be difficult, in part, because management practices are routinely
      utilized in situ to minimize pest injury. If so, then such practices, should, in
      theory, also change with climate, although this has never been quantified.
      Chemical (pesticide) applications remain the primary means of managing pests in
      industrialized countries. While a wide range of climate variables can influence
      chemical use, minimum daily temperature (lowest 24 h recorded temperature in a
      given year) can be associated with the distribution and thermal survival of many
      agricultural pests in temperate regions. The current study quantifies average
      pesticide applications since 1999 for commercial soybean grown over a 2100 km
      North-South latitudinal transect for seven states that varied in minimum daily
      temperature (1999-2013) from -28.6 degrees C (Minnesota) to -5.1 degrees C
      (Louisiana). Although soybean yields (per hectare) did not vary by state, total
      pesticide applications (kg of active ingredient, ai, per hectare) increased from
      4.3 to 6.5 over this temperature range. Significant correlations were observed
      between minimum daily temperatures and kg of ai for all pesticide classes. This
      suggested that minimum daily temperature could serve as a proxy for pesticide
      application. Longer term temperature data (1977-2013) indicated greater relative
      increases in minimum daily temperatures for northern relative to southern states.
      Using these longer-term trends to determine short-term projections of pesticide
      use (to 2023) showed a greater comparative increase in herbicide use for soybean
      in northern; but a greater increase in insecticide and fungicide use for southern
      states in a warmer climate. Overall, these data suggest that increases in
      pesticide application rates may be a means to maintain soybean production in
      response to rising minimum daily temperatures and potential increases in pest
      pressures. 

PMID- 24918586
TI  - Roles for human papillomavirus type 16 l1 cysteine residues 161, 229, and 379 in
      genome encapsidation and capsid stability.
AB  - Human papillomavirus (HPV) capsids are formed through a network of inter- and
      intra-pentameric hydrophobic interactions and disulfide bonds. 72 pentamers of
      the major capsid protein, L1, and an unknown amount of the minor capsid protein,
      L2, form the structure of the capsid. There are 12 conserved L1 cysteine residues
      in HPV16. While C175, C185, and C428 have been implicated in the formation of a
      critical inter-pentameric disulfide bond, no structural or functional roles have
      been firmly attributed to any of the other conserved cysteine residues. Here, we
      show that substitution of cysteine residues C161, C229, and C379 for serine
      hinders the accumulation of endonuclease-resistant genomes as virions mature
      within stratifying and differentiating human epithelial tissue. C229S mutant
      virions form, but are non-infectious. These studies add detail to the
      differentiation-dependent assembly and maturation that occur during the HPV16
      life cycle in human tissue. 

PMID- 24918587
TI  - Structural diversity in the dandelion (Taraxacum officinale) polyphenol oxidase
      family results in different responses to model substrates.
AB  - Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the
      oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most
      plants, PPOs are present as multiple isoenzymes that probably serve distinct
      functions, although the precise relationship between sequence, structure and
      function has not been addressed in detail. We therefore compared the
      characteristics and activities of recombinant dandelion PPOs to gain insight into
      the structure-function relationships within the plant PPO family. Phylogenetic
      analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups.
      More detailed in silico and in vitro analyses of four representative PPOs
      covering both phylogenetic groups were performed. Molecular modeling and docking
      predicted differences in enzyme-substrate interactions, providing a structure
      based explanation for grouping. One amino acid side chain positioned at the
      entrance to the active site (position HB2+1) potentially acts as a "selector" for
      substrate binding. In vitro activity measurements with the recombinant, purified
      enzymes also revealed group-specific differences in kinetic parameters when the
      selected PPOs were presented with five model substrates. The combination of our
      enzyme kinetic measurements and the in silico docking studies therefore indicate
      that the physiological functions of individual PPOs might be defined by their
      specific interactions with different natural substrates. 

PMID- 24918588
TI  - Efficient CRISPR/Cas9-mediated gene editing in Arabidopsis thaliana and
      inheritance of modified genes in the T2 and T3 generations.
AB  - The newly developed CRISPR/Cas9 system for targeted gene knockout or editing has
      recently been shown to function in plants in both transient expression systems as
      well as in primary T1 transgenic plants. However, stable transmission of genes
      modified by the Cas9/single guide RNA (sgRNA) system to the T2 generation and
      beyond has not been demonstrated. Here we provide extensive data demonstrating
      the efficiency of Cas9/sgRNA in causing modification of a chromosomally
      integrated target reporter gene during early development of transgenic
      Arabidopsis plants and inheritance of the modified gene in T2 and T3 progeny.
      Efficient conversion of a nonfunctional, out-of-frame GFP gene to a functional
      GFP gene was confirmed in T1 plants by the observation of green fluorescent
      signals in leaf tissues as well as the presence of mutagenized DNA sequences at
      the sgRNA target site within the GFP gene. All GFP-positive T1 transgenic plants
      and nearly all GFP-negative plants examined contained mutagenized GFP genes.
      Analyses of 42 individual T2 generation plants derived from 6 different T1
      progenitor plants showed that 50% of T2 plants inherited a single T-DNA insert.
      The efficiency of the Cas9/sgRNA system and stable inheritance of edited genes
      point to the promise of this system for facile editing of plant genes. 

PMID- 24918589
TI  - Executive summary: opportunities for action and impact to address HIV and AIDS in
      adolescents.
AB  - INTRODUCTION: The global HIV epidemic in adolescents is not controlled, and this
      group has not received sufficient attention in programming and research efforts
      addressing HIV prevention, treatment, and care. METHODS: A global technical
      consultation on adolescents and HIV addressing services and research gaps was
      convened by United Nations Children's Fund and the London School of Hygiene and
      Tropical Medicine in July 2013. Proceedings from this meeting are presented in
      this issue of the Supplement. RESULTS: Several reviews highlight poor levels of
      coverage of critical HIV prevention, treatment, and care interventions for
      adolescents, disparities in HIV prevalence among adolescent girls, and low-risk
      perceptions associated with risk behaviors among key risk groups. Others
      underscore the significance of clear national targets and strengthening data,
      government involvement, enhanced systems capacity and policy, engagement of
      community and adolescent social networks, and of mobile and internet technologies
      to the success of interventions for adolescents. Finally, reviews identified
      several efficacious interventions for adults that could benefit from operational
      research to inform optimizing implementation in adolescents and how to do so with
      maximal cost efficiency and impact on the epidemic. CONCLUSIONS: Addressing the
      adolescent gap in the response to the HIV epidemic is essential to a more
      sustainable and effective response and is critical to overall adolescent health
      and well-being. The global community has the means and the responsibility to put
      measures in place to make AIDS-free survival the reality for children in this
      second decade of life.

PMID- 24918590
TI  - Epidemiology of HIV and AIDS among adolescents: current status, inequities, and
      data gaps.
AB  - OBJECTIVES: To examine levels and patterns of HIV prevalence, knowledge, sexual
      behavior, and coverage of selected HIV services among adolescents aged 10-19
      years and highlight data gaps and challenges. METHODS: Data were reviewed from
      Joint United Nations Programme on HIV/AIDS HIV estimates, nationally
      representative household surveys, behavioral surveillance surveys, and published
      literature. RESULTS: A number of gaps exist for adolescent-specific HIV-related
      data; however, important implications for programming can be drawn. Eighty-two
      percent of the estimated 2.1 million adolescents aged 10-19 years living with HIV
      in 2012 were in sub-Saharan Africa, and the majority of these (58%) were females.
      Comprehensive accurate knowledge about HIV, condom use, HIV testing, and
      antiretroviral treatment coverage remain low in most countries. Early sexual
      debut (sex before 15 years of age) is more common among adolescent girls than
      boys in low- and middle-income countries, consistent with early marriage and
      early childbirth in these countries. In low and concentrated epidemic countries,
      HIV prevalence is highest among key populations. CONCLUSIONS: Although the
      available HIV-related data on adolescents are limited, increased HIV
      vulnerability in the second decade of life is evident in the data. Improving data
      gathering, analysis, and reporting systems specific to adolescents is essential
      to monitoring progress and improving health outcomes for adolescents. More
      systematic and better quality disaggregated data are needed to understand
      differences by sex, age, geography, and socioeconomic factors and to address
      equity and human rights obligations, especially for key populations.

PMID- 24918591
TI  - Effective approaches for programming to reduce adolescent vulnerability to HIV
      infection, HIV risk, and HIV-related morbidity and mortality: a systematic review
      of systematic reviews.
AB  - BACKGROUND: In 2012, an estimated 2.1 million adolescents were living with HIV.
      Though there are effective interventions to prevent and treat HIV infection,
      adolescents face specific barriers in accessing them. As a result, new infections
      and poor outcomes among HIV-infected adolescents are common. HIV programming for
      adolescents should focus on interventions of proven effectiveness and address
      underlying factors driving incidence and lack of effective treatment and care in
      this age group. METHODS: We conducted a systematic review of systematic reviews
      to summarize the global data on effectiveness of 20 intervention types, to
      identify characteristics of effective interventions, and to explore evidence of
      how adolescents can access interventions with proven effectiveness. Interventions
      were in 2 broad categories: those designed primarily for adults and those
      designed specifically for adolescents. Where available, we evaluated the evidence
      of impact on the key outcomes: HIV risk, HIV transmission, and HIV morbidity and
      mortality. RESULTS: Among the interventions designed for adolescents, there was
      high-quality evidence that in-school interventions and some interventions in
      geographically defined communities can positively impact important HIV-related
      outcomes, such as self-reported sexual risk behaviors. Interventions designed
      primarily for adults that had high-quality, consistent biological evidence of
      efficacy included voluntary medical male circumcision (VMMC), antiretrovirals for
      the prevention of mother-to-child transmission, HIV testing and counseling, HIV
      treatment, condom use, and provision of sterile injecting equipment to people who
      inject drugs. There was also an evidence of potential efficacy for oral
      preexposure prophylaxis and behavior change interventions among certain
      populations. There was a dearth of systematic review data on how best to enable
      adolescents to access the intervention types identified as having proven
      effectiveness among adults. CONCLUSIONS: This series of reviews allowed us to
      rigorously and systematically review a large number of intervention types at once
      using a standard, transparent methodology. Eight key interventions showed clear
      evidence of effectiveness, with evidence of potential efficacy for some
      additional interventions among certain populations. DISCUSSION: These priority
      interventions with proven effectiveness should be included in all HIV prevention
      programming for adolescents. There is a pressing need for more rigorous research
      on how best to enable adolescents to access these effective interventions.

PMID- 24918592
TI  - The impact and cost of the HIV/AIDS investment framework for adolescents.
AB  - BACKGROUND: In 2005, the resources needed to support orphans and vulnerable
      children in sub-Saharan Africa were estimated at US$ 1.1-4.1 billion. Approaches
      to support vulnerable children have changed considerably since then. This study
      updates previous estimates by including new types of support and information on
      support costs. METHODS: We considered 16 types of support categorized as economic
      strengthening, education support, social care and community outreach, and program
      support. The estimates combine the number of children in need of each
      intervention with unit costs derived from the literature and coverage goals based
      on current coverage and feasible future improvements. RESULTS: The number of
      children affected by AIDS in low- and middle-income countries varies from 58
      million to 315 million depending on the definition of need. The resources
      required to provide support to children living in poor households will grow from
      US$ 4.2 billion in 2012 to US$ 5-8 billion by 2020. Almost two-thirds of these
      resources will be needed for Sub-Saharan Africa. The largest needs are for cash
      transfers, community care workers, early childhood development, block grants for
      education, M&E monitoring and evaluation, and direct material support.
      DISCUSSION: The results show that we can significantly improve the coverage of
      services for vulnerable children with only modest increases in resources. This
      results from stable or declining numbers of orphans and children living with HIV
      plus economic growth that is moving more households out of poverty. The results
      also reflect an important shift toward providing support to strengthen families
      and communities that care for children rather than direct material support.
      CONCLUSION: More resources are required to support children affected by AIDS, but
      new approaches to provide that support will be cost effective and have broad
      social and economic benefits.

PMID- 24918593
TI  - What HIV programs work for adolescent girls?
AB  - BACKGROUND: Adolescent girls face unique challenges in reducing their risk of
      acquiring HIV because of gender inequalities, but much of HIV programming and
      evaluation lacks a specific focus on female adolescents. METHODS: This article,
      based on a review of 150 studies and evaluations from 2001 to June 2013, reviews
      evidence on programming for adolescents that is effective for girls or could be
      adapted to be effective for girls. RESULTS: The evidence suggests specific
      interventions for adolescent girls across 3 critical areas: (1) an enabling
      environment, including keeping girls in school, promoting gender equity,
      strengthening protective legal norms, and reducing gender-based violence; (2)
      information and service needs, including provision of age-appropriate
      comprehensive sex education, increasing knowledge about and access to information
      and services, and expanding harm reduction programs for adolescent girls who
      inject drugs; and (3) social support, including promoting caring relationships
      with adults and providing support for adolescent female orphans and vulnerable
      children. DISCUSSION: Numerous gaps remain in evidence-based programming for
      adolescent girls, including a lack of sex- and age-disaggregated data and the
      fact that many programs are not explicitly designed or evaluated with adolescents
      in mind. However, evidence reinforces bolstering critical areas such as
      education, services, and support for adolescent girls. CONCLUSIONS: This article
      contributes to the growing body of literature on HIV and adolescent girls and
      reviews the vulnerabilities of girls, articulates the challenges of programming,
      develops a framework for addressing the needs of girls, and reviews the evidence
      for successful programming for adolescent girls.

PMID- 24918594
TI  - Lessons learned from a review of interventions for adolescent and young key
      populations in Asia Pacific and opportunities for programming.
AB  - BACKGROUND: Over a third of new HIV infections globally are among 15-24 year-olds
      and over 20% among adolescents aged 10-19 years in Asia Pacific. The review was
      initiated to identify interventions in the region with demonstrated or potential
      impact for adolescent and young key populations (YKP) looking at the role of
      individual and structural factors in accessibility and delivery. The review is a
      component of a more comprehensive review undertaken by UNICEF and partners in the
      region. METHODS: This was a desk review of over 1000 articles, and 37 were
      selected. Journal articles in PubMed, Cochrane Library, Cochrane DARE, EMBASE,
      PsycINFO, CINAHL, and Web of Science databases were searched for HIV intervention
      related information for adolescent and YKP. RESULTS AND DISCUSSION: Findings
      showed that except for low levels of risk perception, most individual decisions
      regarding safe behavior and testing uptake were mediated by structural factors.
      Critical enablers such as design and delivery of services, peer education, and
      condom policies were associated with the uptake of high-impact interventions.
      Synergistic development interventions such as sexuality education, rights-based
      enforcement of antitrafficking laws, and addressing violence and abuse could
      increase safer behaviors. CONCLUSIONS: Although structural factors play a key
      role in access and uptake of HIV prevention services for adolescent and YKP,
      further qualitative research is needed to understand and mitigate the drivers of
      vulnerability and constructed perceptions of risk.

PMID- 24918595
TI  - Lessons learned from scale-up of voluntary medical male circumcision focusing on
      adolescents: benefits, challenges, and potential opportunities for linkages with
      adolescent HIV, sexual, and reproductive health services.
AB  - BACKGROUND AND METHODS: By December 2013, it was estimated that close to 6
      million men had been circumcised in the 14 priority countries for scaling up
      voluntary medical male circumcision (VMMC), the majority being adolescents (10-19
      years). This article discusses why efforts to scale up VMMC should prioritize
      adolescent men, drawing from new evidence and experiences at the international,
      country, and service delivery levels. Furthermore, we review the extent to which
      VMMC programs have reached adolescents, addressed their specific needs, and can
      be linked to their sexual and reproductive health and other key services. RESULTS
      AND DISCUSSION: In priority countries, adolescents represent 34%-55% of the
      target population to be circumcised, whereas program data from these countries
      show that adolescents represent between 35% and 74% of the circumcised men. VMMC
      for adolescents has several advantages: uptake of services among adolescents is
      culturally and socially more acceptable than for adults; there are fewer barriers
      regarding sexual abstinence during healing or female partner pressures; VMMC
      performed before the age of sexual debut has maximum long-term impact on reducing
      HIV risk at the individual level and consequently reduces the risk of
      transmission in the population. Offered as a comprehensive package, adolescent
      VMMC can potentially increase public health benefits and offers opportunities for
      addressing gender norms. Additional research is needed to assess whether current
      VMMC services address the specific needs of adolescent clients, to test adapted
      tools, and to assess linkages between VMMC and other adolescent-focused HIV,
      health, and social services.

PMID- 24918596
TI  - Scale-up of adolescent contraceptive services: lessons from a 5-country
      comparative analysis.
AB  - BACKGROUND: Poor sexual and reproductive health outcomes among adolescents aged
      10-19 years are indicative of the barriers this group faces in accessing health
      services and highlights a gap in the availability of appropriate services,
      including adolescent-friendly contraceptive services (AFCS). The HIV Investment
      Framework identifies contraceptive services as an entry point for HIV counseling,
      testing, and treatment, and as a component of HIV prevention. To effectively meet
      the needs of adolescents, greater understanding of effective scale-up strategies
      for adolescent-friendly services is needed. METHODS: The authors conducted a
      retrospective analysis of AFCS scale-up experiences in Ethiopia, Ghana,
      Mozambique, Tanzania, and Vietnam using the ExpandNet/World Health Organization
      framework for systematic scale-up. The authors analyzed the type of scale
      (expansion or institutionalization), dissemination and advocacy, organizational
      process, costs and resource mobilization, and monitoring and evaluation. RESULTS:
      The analysis showed that all programs simultaneously pursued expansion and
      institutionalization, contributing to sustainable scale-up. Advocacy complemented
      by intensive capacity building at all levels of the health system contributed to
      adoption of AFCS in national and district work plans and budgets as well
      strengthening collection of age-disaggregated data. DISCUSSION: To achieve scale
      up of AFCS, the authors identified the importance of institutionalization and
      expansion in tandem for synergy and reinforcement, empowering adolescents to be
      agents of change and hold government accountable to its commitments, and
      strengthening health systems to sustain AFCS. CONCLUSIONS: This article
      contributes to a growing body of evidence around scale-up of AFCS, which can
      inform the implementation and sustainable scale-up of HIV and other services for
      adolescents.

PMID- 24918597
TI  - Lessons learned from HPV vaccine delivery in low-resource settings and
      opportunities for HIV prevention, treatment, and care among adolescents.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccines to prevent cervical cancer have
      become available in recent years and presented a new challenge to health systems,
      since they prevent a sexually transmitted virus and are most effective if they
      are delivered to young adolescent girls, a group not widely served by other
      health programs. Demonstration and pilot HPV vaccination programs undertaken in
      the past 7-8 years in low-resource settings have produced lessons that may be
      more broadly applied to other adolescent health interventions, particularly to
      those that attempt to reduce human immunodeficiency virus (HIV) infection.
      METHODS: A systematic literature review was undertaken to identify formal and
      informal evaluations of HPV vaccine use in low- and middle-income countries.
      Special attention was devoted to the detailed evaluations carried out on large
      demonstration projects in India, Peru, Uganda, and Vietnam. RESULTS: These
      lessons fall into 2 main categories: service delivery operations and community
      outreach and mobilization. Operational issues included venue and timing of
      vaccinations, definition of target population, micro-planning and coordination,
      integration with other services, and training. Community issues included consent,
      messages and channels, endorsement and support, and timing of mobilization
      efforts. DISCUSSION: Careful planning, good coordination across sectors and
      levels, and sensitive attention to the expressed needs for information and
      preferences for communication channels among youth, parents, and communities more
      broadly were among the key lessons that are relevant for HIV interventions, but
      many of the smaller details were also important. CONCLUSIONS: Applying or
      adapting these lessons to adolescent HIV services could accelerate effective
      program design and enhance success.

PMID- 24918598
TI  - Preventing sexual violence and HIV in children.
AB  - BACKGROUND: Evidence linking violence against women and HIV has grown, including
      on the cycle of violence and the links between violence against children and
      women. To create an effective response to the HIV epidemic, it is key to prevent
      sexual violence against children and intimate partner violence (IPV) against
      adolescent girls. METHODS: Authors analyzed data from national household surveys
      on violence against children undertaken by governments in Swaziland, Tanzania,
      Kenya, and Zimbabwe, with support of the Together for Girls initiative, as well
      as an analysis of evidence on effective programmes. RESULTS: Data show that
      sexual and physical violence in childhood are linked to negative health outcomes,
      including increased sexual risk taking (eg, inconsistent condom use and increased
      number of sexual partners), and that girls begin experiencing IPV (emotional,
      physical, and sexual) during adolescence. Evidence on effective programmes
      addressing childhood sexual violence is growing. Key interventions focus on
      increasing knowledge among children and caregivers by addressing attitudes and
      practices around violence, including dating relationships. Programmes also seek
      to build awareness of services available for children who experience violence.
      DISCUSSION: Findings include incorporating attention to children into HIV and
      violence programmes directed to adults; increased coordination and leveraging of
      resources between these programmes; test transferability of programmes in low-
      and middle-income countries; and invest in data collection and robust evaluations
      of interventions to prevent sexual violence and IPV among children. CONCLUSIONS:
      This article contributes to a growing body of evidence on the prevention of
      sexual violence and HIV in children.

PMID- 24918599
TI  - Commentary: Innovations in programming for HIV among adolescents: towards an AIDS
      free generation.

PMID- 24918600
TI  - Evidence-based programming for adolescent HIV prevention and care: operational
      research to inform best practices.
AB  - BACKGROUND: Globally, a staggering number of adolescents, approximately 2.1
      million, were estimated to be living with HIV in 2012. Unique developmental,
      psychosocial, and environmental considerations make them particularly vulnerable
      to HIV acquisition and argue for a comprehensive response to address this
      burgeoning problem. METHODS: This article explores the current state of the
      science of HIV prevention, treatment, and care for adolescents and identifies
      opportunities to address knowledge gaps and improve health outcomes for this age
      group. RESULTS: Over the past decade, several important milestones have been
      achieved in HIV prevention and care among adults, and despite evidence that
      adherence to care and medications among affected adolescents is significantly
      compromised, critical research among adolescents and young adults substantially
      lags behind. Operational research, in particular, is crucial to understanding how
      to use effective services and interventions for HIV prevention and care safely
      and effectively for adolescents who are in dire need. CONCLUSIONS: Operational
      research among adolescent populations affected by HIV is critically needed to
      close the knowledge and investment gaps, and scale-up efforts for HIV prevention,
      treatment, care, and support for this vulnerable age group.

PMID- 24918601
TI  - Unidirectional P-body transport during the yeast cell cycle.
AB  - P-bodies belong to a large family of RNA granules that are associated with post
      transcriptional gene regulation, conserved from yeast to mammals, and influence
      biological processes ranging from germ cell development to neuronal plasticity.
      RNA granules can also transport RNAs to specific locations. Germ granules
      transport maternal RNAs to the embryo, and neuronal granules transport RNAs long
      distances to the synaptic dendrites. Here we combine microfluidic-based
      fluorescent microscopy of single cells and automated image analysis to follow p
      body dynamics during cell division in yeast. Our results demonstrate that these
      highly dynamic granules undergo a unidirectional transport from the mother to the
      daughter cell during mitosis as well as a constrained "hovering" near the bud
      site half an hour before the bud is observable. Both behaviors are dependent on
      the Myo4p/She2p RNA transport machinery. Furthermore, single cell analysis of
      cell size suggests that PBs play an important role in daughter cell growth under
      nutrient limiting conditions. 

PMID- 24918602
TI  - The gut flora is required for the control of intestinal infection by poly(I:C)
      administration in neonates.
AB  - We found that immunostimulation of the intestinal immune system of neonatal mice
      by poly(I:C) injection decreased intestinal infection by the parasite
      Cryptosporidium parvum. We showed that the presence of dendritic cells and the
      cooperation of mutually dependent cytokines, such as IL-12p40, and type I and
      type II IFNs, were involved in the mechanism of protection induced by poly(I:C).
      This protection is dependent not only on TLR3-TRIF signaling, but also on the
      activation of the TLR5-MyD88 pathway by gut microbiota. These results raise the
      possibility that flagellated intestinal commensal bacteria may, in the presence
      of natural or synthetic agonists of TLR3, provide synergy between the TRIF and
      MyD88 signaling pathways, thereby favoring the development of mucosal defenses.
      In this addendum, we summarize these recent findings and discuss their
      implications for neonatal infections and immunomodulatory strategies. 

PMID- 24918603
TI  - Dasatinib accelerates valproic acid-induced acute myeloid leukemia cell death by
      regulation of differentiation capacity.
AB  - Dasatinib is a compound developed for chronic myeloid leukemia as a multi
      targeted kinase inhibitor against wild-type BCR-ABL and SRC family kinases.
      Valproic acid (VPA) is an anti-epileptic drug that also acts as a class I histone
      deacetylase inhibitor. The aim of this research was to determine the anti
      leukemic effects of dasatinib and VPA in combination and to identify their
      mechanism of action in acute myeloid leukemia (AML) cells. Dasatinib was found to
      exert potent synergistic inhibitory effects on VPA-treated AML cells in
      association with G1 phase cell cycle arrest and apoptosis induction involving the
      cleavage of poly (ADP-ribose) polymerase and caspase-3, -7 and -9. Dasatinib/VPA
      induced cell death thus occurred via caspase-dependent apoptosis. Moreover,
      MEK/ERK and p38 MAPK inhibitors efficiently inhibited dasatinib/VPA-induced
      apoptosis. The combined effect of dasatinib and VPA on the differentiation
      capacity of AML cells was more powerful than the effect of each drug alone, being
      sufficiently strong to promote AML cell death through G1 cell cycle arrest and
      caspase-dependent apoptosis. MEK/ERK and p38 MAPK were found to control
      dasatinib/VPA-induced apoptosis as upstream regulators, and co-treatment with
      dasatinib and VPA to contribute to AML cell death through the regulation of
      differentiation capacity. Taken together, these results indicate that combined
      dasatinib and VPA treatment has a potential role in anti-leukemic therapy. 

PMID- 24918605
TI  - Single- and multi-channel modulation detection in cochlear implant users.
AB  - Single-channel modulation detection thresholds (MDTs) have been shown to predict
      cochlear implant (CI) users' speech performance. However, little is known about
      multi-channel modulation sensitivity. Two factors likely contribute to
      multichannel modulation sensitivity: multichannel loudness summation and the
      across-site variance in single-channel MDTs. In this study, single- and multi
      channel MDTs were measured in 9 CI users at relatively low and high presentation
      levels and modulation frequencies. Single-channel MDTs were measured at widely
      spaced electrode locations, and these same channels were used for the
      multichannel stimuli. Multichannel MDTs were measured twice, with and without
      adjustment for multichannel loudness summation (i.e., at the same loudness as for
      the single-channel MDTs or louder). Results showed that the effect of
      presentation level and modulation frequency were similar for single- and multi
      channel MDTs. Multichannel MDTs were significantly poorer than single-channel
      MDTs when the current levels of the multichannel stimuli were reduced to match
      the loudness of the single-channel stimuli. This suggests that, at equal
      loudness, single-channel measures may over-estimate CI users' multichannel
      modulation sensitivity. At equal loudness, there was no significant correlation
      between the amount of multichannel loudness summation and the deficit in
      multichannel MDTs, relative to the average single-channel MDT. With no loudness
      compensation, multichannel MDTs were significantly better than the best single
      channel MDT. The across-site variance in single-channel MDTs varied substantially
      across subjects. However, the across-site variance was not correlated with the
      multichannel advantage over the best single channel. This suggests that CI
      listeners combined envelope information across channels instead of attending to
      the best channel. 

PMID- 24918606
TI  - Individual investigator profiles of biospecimen use in cancer research.
AB  - BACKGROUND: Establishing targets for case accrual is an important component of a
      strategic plan for a biobank. We have previously assessed overall patterns of
      biospecimen use in cancer research publications in selected journals. Here we
      extend this analysis to consider patterns of biospecimen use in relation to
      cancer research programs developed by individual investigators. METHODS: We
      selected three individual cancer research investigators whose independent
      research programs began circa 1986, have been characterized by extensive use of
      human tumor biospecimens, and have primarily involved translational research in
      the areas of breast, lung, and ovarian cancer. We analyzed biospecimen and data
      usage in their career publications categorized by numbers, type, and format, and
      accompanying annotating data in terms of conformance with BRISQ reporting and
      ethics related criteria. RESULTS: Biospecimens were used in 313/474 (66%) of
      publications analyzed. The average number of biospecimens used by these research
      programs increased six-fold from less than 1000 in 2001-2003 to greater than 6000
      in 2010-2012, and the average cohort sizes per article also increased from
      approximately 50 to 200 cases per study over the same period in most biospecimen
      categories (p<0.05). The relative proportions of different formats of
      biospecimens used has varied significantly and continues to change with the
      emergence of digital biospecimen derived data. In these three translational
      research programs, BRISQ elements relating to 'Biobank' categories were
      significantly less well reported for biospecimens used in publications than data
      corresponding to 'Clinical chart' categories (p<0001). CONCLUSIONS: This study
      shows that overall use of biospecimens in cancer research has increased
      significantly and that dynamic variation in the relative use of different
      biospecimen formats has also occurred. This study also confirms our previous
      findings on patterns of biospecimen use and also those concerning incomplete
      reporting of relevant data elements that has not improved in the past decade.

PMID- 24918607
TI  - Seasonal blowfly distribution and abundance in fragmented landscapes. Is it
      useful in forensic inference about where a corpse has been decaying?
AB  - Blowflies are insects of forensic interest as they may indicate characteristics
      of the environment where a body has been laying prior to the discovery. In order
      to estimate changes in community related to landscape and to assess if blowfly
      species can be used as indicators of the landscape where a corpse has been
      decaying, we studied the blowfly community and how it is affected by landscape in
      a 7,000 km2 region during a whole year. Using baited traps deployed monthly we
      collected 28,507 individuals of 10 calliphorid species, 7 of them well
      represented and distributed in the study area. Multiple Analysis of Variance
      found changes in abundance between seasons in the 7 analyzed species, and changes
      related to land use in 4 of them (Calliphora vomitoria, Lucilia ampullacea, L.
      caesar and L. illustris). Generalised Linear Model analyses of abundance of these
      species compared with landscape descriptors at different scales found only a
      clear significant relationship between summer abundance of C. vomitoria and
      distance to urban areas and degree of urbanisation. This relationship explained
      more deviance when considering the landscape composition at larger geographical
      scales (up to 2,500 m around sampling site). For the other species, no clear
      relationship between land uses and abundance was found, and therefore observed
      changes in their abundance patterns could be the result of other variables,
      probably small changes in temperature. Our results suggest that blowfly community
      composition cannot be used to infer in what kind of landscape a corpse has
      decayed, at least in highly fragmented habitats, the only exception being the
      summer abundance of C. vomitoria. 

PMID- 24918608
TI  - Response to Diaz-Arrastia et al., "Pharmacotherapy of traumatic brain injury:
      state of the science and the road forward".

PMID- 24918609
TI  - Viruses in maize and Johnsongrass in southern Ohio.
AB  - The two major U.S. maize viruses, Maize dwarf mosaic virus (MDMV) and Maize
      chlorotic dwarf virus (MCDV), emerged in southern Ohio and surrounding regions in
      the 1960s and caused significant losses. Planting resistant varieties and
      changing cultural practices has dramatically reduced virus impact in subsequent
      decades. Current information on the distribution, diversity, and impact of known
      and potential U.S. maize disease-causing viruses is lacking. To assess the
      current reservoir of viruses present at the sites of past disease emergence, we
      used a combination of serological testing and next-generation RNA sequencing
      approaches. Here, we report enzyme-linked immunosorbent assay and RNA-Seq data
      from samples collected over 2 years to assess the presence of viruses in
      cultivated maize and an important weedy reservoir, Johnsongrass (Sorghum
      halepense). Results revealed a persistent reservoir of MDMV and two strains of
      MCDV in Ohio Johnsongrass. We identified sequences of several other grass
      infecting viruses and confirmed the presence of Wheat mosaic virus in Ohio maize.
      Together, these results provide important data for managing virus disease in
      field corn and sweet corn maize crops, and identifying potential future virus
      threats.

PMID- 24918611
TI  - Determinants of C1q binding in the single antigen bead assay.
AB  - BACKGROUND: A modified single antigen bead (SAB) assay measuring C1q binding to
      human leukocyte antigen antibodies has recently been introduced. The aim of this
      study was to investigate the determinants of C1q binding on SAB. METHODS: Sera
      from 73 sensitized patients were analyzed by the generic IgGpan as well as IgG
      subclass specific SAB assays and correlated with the standard and an anti-human
      globulin (AHG) enhanced C1q test. RESULTS: Among 2,665 SABs with positive IgGpan
      results (mean fluorescence intensity [MFI]>500), strong complement-binding IgG1
      and IgG3 subclasses accounted for a median of 99% (interquartile range, 76%-100%)
      of the total IgG amount. IgGpan MFI alone showed a very strong association with
      standard C1q positivity (r=0.72), which was superior to a model including all IgG
      subclass MFI (r=0.62). Combining all IgG subclass MFI and IgGpan MFI only
      marginally improved the prediction of standard C1q positivity compared with
      IgGpan MFI alone (Deltar=0.02). IgGpan MFI greater than 14,154 predicted standard
      C1q positivity, with 92% sensitivity and 96% specificity. Notably, 1,840 (93%) of
      the 1,974 C1q-negative SABs contained human leukocyte antigen antibodies with
      strong complement-binding IgG1 and IgG3 subclasses. Anti-human globulin
      significantly enhanced the signal in the C1q assay, but the association of AHG
      C1q positivity with IgGpan MFI was less strong (r=0.51). CONCLUSION: C1q binding
      on SAB is strongly associated with IgGpan MFI. IgG subclass information only
      marginally improves prediction of C1q binding likely because complement-binding
      IgG1 and IgG3 subclasses dominate regarding frequency and relative amounts. A
      negative C1q assay result does not indicate the absence of strong complement
      binding IgG subclasses.

PMID- 24918612
TI  - Death by donation: reflections on individual authorization, assisted suicide and
      organ donation.

PMID- 24918610
TI  - Associations of anthropometric factors with KRAS and BRAF mutation status of
      primary colorectal cancer in men and women: a cohort study.
AB  - Obesity is a well-established risk factor for colorectal cancer (CRC), and
      accumulating evidence suggests a differential influence of sex and anthropometric
      factors on the molecular carcinogenesis of the disease. The aim of the present
      study was to investigate the relationship between height, weight, bodyfat
      percentage, waist- and hip circumference, waist-hip ratio (WHR), body mass index
      (BMI) and CRC risk according to KRAS and BRAF mutation status of the tumours,
      with particular reference to potential sex differences. KRAS and BRAF mutations
      were analysed by pyrosequencing in tumours from 494 incident CRC cases in the
      Malmo Diet and Cancer Study. Hazard ratios of CRC risk according to
      anthropometric factors and mutation status were calculated using multivariate Cox
      regression models. While all anthropometric measures except height were
      associated with an increased risk of KRAS-mutated tumours, only BMI was
      associated with an increased risk of KRAS wild type tumours overall. High weight,
      hip, waist, WHR and BMI were associated with an increased risk of BRAF wild type
      tumours, but none of the anthropometric factors were associated with risk of BRAF
      mutated CRC, neither in the overall nor in the sex-stratified analysis. In men,
      several anthropometric measures were associated with both KRAS-mutated and KRAS
      wild type tumours. In women, only a high WHR was significantly associated with an
      increased risk of KRAS-mutated CRC. A significant interaction was found between
      sex and BMI with respect to risk of KRAS-mutated tumours. In men, all
      anthropometric factors except height were associated with an increased risk of
      BRAF wild type tumours, whereas in women, only bodyfat percentage was associated
      with an increased risk of BRAF wild type tumours. The results from this
      prospective cohort study further support an influence of sex and lifestyle
      factors on different pathways of colorectal carcinogenesis, defined by KRAS and
      BRAF mutation status of the tumours. 

PMID- 24918613
TI  - Serine protease inhibitor-6 inhibits granzyme B-mediated injury of renal tubular
      cells and promotes renal allograft survival.
AB  - BACKGROUND: Protease inhibitor 9 (PI-9) is an intracellular serpin that
      specifically inhibits granzyme B, a cytotoxic serine protease found in the
      cytosolic granules of cytotoxic T lymphocytes and natural killer cells. Enhanced
      cortical expression of PI-9 has been observed in kidney allografts with
      subclinical rejection, suggesting that the tubular epithelial cell (TEC)
      expression of this protein may have a protective role and attenuate overt
      allograft rejection. METHODS AND RESULTS: We demonstrate that TEC express SPI-6
      protein, the murine homolog of PI-9, basally with a modest increase after
      cytokine exposure. Tubular epithelial cell expression of SPI-6 blocks granzyme B
      mediated death because TEC from SPI-6 null kidneys have increased susceptibility
      to cytotoxic CD8+ cells in vitro. The role of SPI-6 was tested in a mouse kidney
      transplant model using SPI-6 null or wild type donor kidneys (H-2) into
      nephrectomized recipients (H-2). SPI-6 null kidney recipients demonstrated
      reduced renal function at day 8 after transplantation compared to controls
      (creatinine, 113+/-23 vs. 28+/-3 MUmol/L; n=5; P<0.01), consistent with observed
      tubular injury and extensive mononuclear cell infiltration. Loss of donor kidney
      SPI-6 shortened graft survival time (20+/-19 vs. 66+/-33 days; n=8-10; P<0.001).
      CONCLUSION: Our data show for the first time that resistance of kidney TEC to
      cytotoxic T-cell granzyme B-induced death in vitro and in vivo is mediated by the
      expression of SPI-6. We suggest that SPI-6 is an important endogenous mechanism
      to prevent rejection injury from perforin or granzyme B effectors and enhanced PI
      9 or SPI-6 expressions by TEC may provide protection from diverse forms of
      inflammatory kidney injury and promote long-term allograft survival.

PMID- 24918614
TI  - Questioning the added value of Luminex single antigen beads to detect C1q binding
      donor HLA-specific antibodies.

PMID- 24918615
TI  - Sirtuin 1 activation stimulates mitochondrial biogenesis and attenuates renal
      injury after ischemia-reperfusion.
AB  - BACKGROUND: Renal ischemia-reperfusion (I/R) is a major contributor to delayed
      graft function after renal transplantation. The pathophysiology of I/R can be
      summarized by a primary energy deficit during ischemia and a secondary phase of
      oxidative stress and inflammation. Sirtuin 1 is an energy-sensing enzyme involved
      in regulating multiple cellular functions. We hypothesized that stimulating
      Sirtuin 1 would increase mitochondrial biogenesis thereby enhancing energy
      metabolism and attenuating I/R-induced renal injury. METHODS: Adult male rats
      were subjected to 60 min of bilateral renal pedicle clamping. SRT1720 (5 mg/kg
      body weight) or vehicle (20% dimethyl sulfoxide in saline) was administered
      intravenously at reperfusion. Blood and renal tissues were collected 24 hr after
      reperfusion. RESULTS: Posttreatment with SRT1720 significantly improved renal
      histologic architecture, decreased apoptosis, and reduced serum aspartate
      aminotransferase and creatinine levels compared to the vehicle. Renal adenosine
      triphosphate (ATP) levels were reduced by 48% after I/R, whereas SRT1720 restored
      ATP to 77% of control. Further, SRT1720 reversed the loss of renal mitochondrial
      mass induced by I/R supported by an increased expression of peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha and its downstream
      mediators. SRT1720 also increased ATP levels and mitochondrial mass in human
      renal HK-2 cells. Moreover, SRT1720 decreased the levels of malondialdehyde,
      nitrotyrosine, and inducible nitric oxide synthase expression compared to the
      vehicle. A marked decrease in macrophage infiltration by SRT1720 treatment was
      associated with a decrease in tumor necrosis factor-alpha expression and a
      decrease in IkappaB-alpha degradation and nuclear factor-kappaB phosphorylation
      after I/R. CONCLUSION: SRT1720 treatment enhanced energy metabolism by
      stimulating mitochondrial biogenesis as well as decreasing nitrosative stress and
      inflammation, thereby attenuating I/R-induced renal injury.

PMID- 24918616
TI  - Simultaneous transplantation of hematopoietic stem cells and a vascularized
      composite allograft leads to tolerance.
AB  - BACKGROUND: We have previously demonstrated that tolerance to a vascularized
      composite allograft (VCA) can be achieved after the establishment of mixed
      chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte
      antigen-matched canine model is not dependent on the previous establishment of
      mixed chimerism and can be induced coincident with hematopoietic cell
      transplantation (HCT). METHODS: Eight dog leukocyte antigen-matched, minor
      antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four
      dogs received donor bone marrow at the time of VCA transplantation (group 1),
      whereas a second group of four dogs did not (group 2). All recipients received a
      limited course of postgrafting immunosuppression. All dogs that received HCT and
      VCA were given donor, third-party, and autologous skin grafts. RESULTS: All group
      1 recipients were tolerant to their VCA (>62 weeks). Three of the four dogs in
      group 2 rejected their VCA transplants after the cessation of immunosuppression.
      Biopsies obtained from the muscle and skin of VCA from group 1 showed few
      infiltrating cells compared with extensive infiltrates in biopsies of VCA from
      group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+
      T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT
      recipients. All group 1 animals were tolerant to their donor skin graft and
      promptly rejected the third-party skin grafts. CONCLUSION: These data
      demonstrated that donor-specific tolerance to all components of the VCA can be
      established through simultaneous nonmyeloablative allogeneic HCT and VCA
      transplantation protocol.

PMID- 24918617
TI  - The combined risk of donor quality and recipient age: higher-quality kidneys may
      not always improve patient and graft survival.
AB  - BACKGROUND: The Kidney Donor Profile Index (KDPI) is a more precise donor organ
      quality metric replacing age-based characterization of donor risk. Little prior
      attention has been paid on the outcomes of lower-quality kidneys transplanted
      into elderly recipients. Although we have previously shown that immunological
      risks associated with older organs are attenuated by advanced recipient age, it
      remains unknown whether risks associated with lower-quality KDPI organs are
      similarly reduced in older recipients. METHODS: Donor organ quality as measured
      by the KDPI was divided into quintiles (very high, high, medium, low, and very
      low quality), and Cox proportional hazards was used to assess graft and recipient
      survival in first-time adult deceased donor transplant recipients by recipient
      age. RESULTS: In uncensored graft survival analysis, recipients older than 69
      years had demonstrated comparable outcomes if they received low-quality kidneys
      compared to medium-quality kidneys. Death-censored analysis demonstrated no
      increased relative risk when low-quality kidneys were transplanted into
      recipients aged 70 to 79 years (hazard ratio [HR], 1.11; P=0.19) or older than 79
      years (HR, 1.08; P=0.59). In overall survival analysis, elderly recipients gained
      no relative benefit from medium-quality kidneys over low-quality kidneys (70-79
      years: HR, 1.03, P=0.51; >79 years: HR, 1.08; P=0.32). CONCLUSION: Our analysis
      demonstrates that transplanting medium-quality kidneys into elderly recipients
      does not provide significant advantage over low-quality kidneys.

PMID- 24918618
TI  - Low-serum testosterone levels pre-liver transplantation are associated with
      reduced rates of early acute allograft rejection in men.
AB  - BACKGROUND: Low pretransplant serum testosterone has recently been associated
      with increased mortality in men awaiting liver transplantation, but the potential
      impact on rejection has not yet been investigated. METHODS: Pretransplantation
      serum testosterone, SHBG, and other variables were collected on 190 consecutive
      men who received a liver transplant between 2007 and 2013. Rates of subsequent
      acute cellular rejection were recorded. Multivariable analysis was performed to
      define variables associated with rejection and other clinically important end
      points. RESULTS: Thirty (16%) of 190 men experienced acute cellular rejection.
      Lower pretransplant testosterone was associated with lower rejection rates, -7%
      (95% confidence interval [CI], -2% to -12%) per nmol/L decrease in total
      testosterone and -4% (95% CI, -0.5% to -7%) per 10 pmol/L decrease in free
      testosterone. Total testosterone (correlation 0.29, P=0.04) and free testosterone
      (correlation 0.37, P=0.01) correlated significantly with the histological
      severity of rejection. Older age at transplant (+5% [95% CI, 9%-2%]) per year,
      and nonautoimmune etiology of liver disease (OR, 1.0 for autoimmune, 0.22 [95%
      CI, 0.07-0.73] for hepatitis C virus, and 0.58 [95% CI, 0.21-1.71] for other
      etiologies) were also associated with decreased rejection risk. In a generalized
      linear model including the covariates testosterone, SHBG, age, etiology, and
      MELD, total testosterone remained a significant predictor of rejection (adjusted
      OR, 1.06; P=0.03), as did age at transplant (OR, 0.95; P=0.01). CONCLUSION: Low
      preliver transplant serum testosterone independently predicts a decreased risk of
      acute allograft rejection. Whether testosterone is a marker of disease-associated
      immune dysfunction or has immune-modulatory effects requires further study.

PMID- 24918619
TI  - Prediction of death in less than 60 minutes after withdrawal of cardiorespiratory
      support in potential organ donors after circulatory death.
AB  - BACKGROUND: Given the stable number of potential organ donors after brain death,
      donors after circulatory death have been an increasing source of organs procured
      for transplant. Among the most important considerations for donation after
      circulatory death (DCD) is the prediction that death will occur within a
      reasonable period of time after the withdrawal of cardiorespiratory support
      (WCRS). Accurate prediction of time to death is necessary for the procurement
      process. We aimed to develop simple predictive rules for death in less than 60
      min and test the accuracy of these rules in a pool of potential DCD donors.
      METHODS: A multicenter prospective longitudinal cohort design of DCD eligible
      patients (n=318), with the primary binary outcome being death in less than 60 min
      after withdrawal of cardiorespiratory support conducted in 28 accredited
      intensive care units (ICUs) in Australia. We used a random split-half method to
      produce two samples, first to develop the predictive classification rules and
      then to estimate accuracy in an independent sample. RESULTS: The best
      classification model used only three simple classification rules to produce an
      overall efficiency of 0.79 (0.72-0.85), sensitivity of 0.82 (0.73-0.90), and a
      positive predictive value of 0.80 (0.70-0.87) in the independent sample. Using
      only intensive care unit specialist prediction (a single classification rule)
      produced comparable efficiency 0.80 (0.73-0.86), sensitivity 0.87 (0.78-0.93),
      and positive predictive value 0.78 (0.68-0.86). CONCLUSION: This best predictive
      model missed only 18% of all potential donors. A positive prediction would be
      incorrect on only 20% of occasions, meaning there is an acceptable level of lost
      opportunity costs involved in the unnecessary assembly of transplantation teams
      and theatres.

PMID- 24918620
TI  - The "metabolic winter" hypothesis: a cause of the current epidemics of obesity
      and cardiometabolic disease.
AB  - The concept of the "Calorie" originated in the 1800 s in an environment with
      limited food availability, primarily as a means to define economic equivalencies
      in the energy density of food substrates. Soon thereafter, the energy densities
      of the major macronutrients-fat, protein, and carbohydrates-were defined.
      However, within a few decades of its inception, the "Calorie" became a commercial
      tool for industries to promote specific food products, regardless of health
      benefit. Modern technology has altered our living conditions and has changed our
      relationship with food from one of survival to palatability. Advances in
      agriculture, food manufacturing, and processing have ensured that calorie
      scarcity is less prevalent than calorie excess in the modern world. Yet, many
      still approach dietary macronutrients in a reductionist manner and assume that
      isocalorie foodstuffs are isometabolic. Herein, we discuss a novel way to view
      the major food macronutrients and human diet in this era of excessive caloric
      consumption, along with a novel relationship among calorie scarcity, mild cold
      stress, and sleep that may explain the increasing prevalence of nutritionally
      related diseases.

PMID- 24918621
TI  - Bird community conservation and carbon offsets in western North America.
AB  - Conservation initiatives to protect and restore valued species and communities in
      human-dominated landscapes face huge challenges linked to the cost of acquiring
      habitat. We ask how the sale of forest carbon offsets could reduce land
      acquisition costs, and how the alternate goals of maximizing alpha or beta
      diversity in focal communities could affect the prioritization land parcels over
      a range of conservation targets. Maximizing total carbon storage and carbon
      sequestration potential reduced land acquisition costs by up to 48%. Maximizing
      beta rather than alpha-diversity within forest and savannah bird communities
      reduced acquisition costs by up to 15%, and when these solutions included
      potential carbon credit revenues, acquisition cost reductions up to 32% were
      achieved. However, the total cost of conservation networks increased
      exponentially as area targets increased in all scenarios. Our results indicate
      that carbon credit sales have the potential to enhance conservation outcomes in
      human-dominated landscapes by reducing the net acquisition costs of land
      conservation in old and maturing forests essential for the persistence of old
      forest plant and animal communities. Maximizing beta versus alpha-diversity may
      further reduce costs by reducing the total area required to meet conservation
      targets and enhancing landscape heterogeneity. Although the potential value of
      carbon credit sales declined as a fraction of total acquisition costs, even
      conservative scenarios using a carbon credit value of $12.5/T suggest reductions
      in acquisition cost of up to $235 M, indicating that carbon credit sales could
      substantially reduce the costs of conservation. 

PMID- 24918623
TI  - Chemical interactions between Nano-ZnO and Nano-TiO2 in a natural aqueous medium.
AB  - The use of diverse engineered nanomaterials (ENMs) potentially leads to the
      release of multiple ENMs into the environment. However, previous efforts to
      understand the behavior and the risks associated with ENMs have focused on only
      one material at a time. In this study, the chemical interactions between two of
      the most highly used ENMs, nano-TiO2, and nano-ZnO, were examined in a natural
      water matrix. The fate of nano-ZnO in Lake Michigan water was investigated in the
      presence of nano-TiO2. Our experiments demonstrate that the combined effects of
      ZnO dissolution and Zn adsorption onto nano-TiO2 control the concentration of
      dissolved zinc. X-ray absorption spectroscopy was used to determine the
      speciation of Zn in the particulate fraction. The spectra show that Zn partitions
      between nano-ZnO and Zn2+ adsorbed on nano-TiO2. A simple kinetic model is
      presented to explain the experimental data. It integrates the processes of nano
      ZnO dissolution with Zn adsorption onto nano-TiO2 and successfully predicts
      dissolved Zn concentration in solution. Overall, our results suggest that the
      fate and toxicity potential of soluble ENMs, such as nano-ZnO, are likely to be
      influenced by the presence of other stable ENMs, such as nano-TiO2.

PMID- 24918622
TI  - The use of longitudinal 18F-FET MicroPET imaging to evaluate response to
      irinotecan in orthotopic human glioblastoma multiforme xenografts.
AB  - OBJECTIVES: Brain tumor imaging is challenging. Although 18F-FET PET is widely
      used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in
      xenograft has not been assessed to date. The aim of this study therefore was to
      evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment
      response in xenografts. In addition, the correlations between the 18F-FET tumor
      accumulation and the gene expression of Ki67 and the amino acid transporters LAT1
      and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in
      xenograft and archival patient tumors was compared. METHODS: Human GBM cells were
      injected orthotopically in nude mice and 18F-FET uptake was followed by weekly
      MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or
      saline weekly. After two weeks of treatment the brain tumors were isolated and
      quantitative polymerase chain reaction were performed on the xenograft tumors and
      in parallel on archival patient tumor specimens. RESULTS: The relative tumor-to
      brain (T/B) ratio of SUV max was significantly lower after one week (123 +/- 6%,
      n = 7 vs. 147 +/- 6%, n = 7; p = 0.018) and after two weeks (142 +/- 8%, n = 5
      vs. 204 +/- 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control
      group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = 
      0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a
      strong positive correlation between LAT1 and Ki67 was detected in xenografts.
      Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression
      of LAT2 were observed in patient specimens compared to xenografts. CONCLUSIONS:
      18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM
      xenografts. The strong negative correlation between SUV max T/B ratio and
      LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may
      be used for detection of early treatment response in patients.

PMID- 24918624
TI  - Middle East respiratory syndrome coronavirus (MERS-CoV) infection: chest CT
      findings.
AB  - OBJECTIVE: The purpose of this study was to describe the chest CT findings in
      seven patients with Middle East respiratory syndrome coronavirus (MERS-CoV)
      infection. CONCLUSION: The most common CT finding in hospitalized patients with
      MERS-CoV infection is that of bilateral predominantly subpleural and basilar
      airspace changes, with more extensive ground-glass opacities than consolidation.
      The subpleural and peribronchovascular predilection of the abnormalities is
      suggestive of an organizing pneumonia pattern.

PMID- 24918625
TI  - They are laughing at me: cerebral mediation of cognitive biases in social
      anxiety.
AB  - The fear of embarrassment and humiliation is the central element of social
      anxiety. This frequent condition is associated with cognitive biases indicating
      increased sensitivity to signals of social threat, which are assumed to play a
      causal role in the maintenance of social anxiety. Here, we employed laughter, a
      potent medium for the expression of acceptance and rejection, as an experimental
      stimulus in participants selected for varying degrees of social anxiety to
      identify cerebral mediators of cognitive biases in social anxiety using
      functional magnetic resonance imaging in combination with mediation analysis. We
      directly demonstrated that cerebral activation patterns within the dorsal
      attention network including the left dorsolateral and dorsomedial prefrontal
      cortex mediate the influence of social anxiety on laughter perception. This
      mediation proved to be specific for social anxiety after correction for measures
      of general state and trait anxiety and occurred most prominently under bimodal
      audiovisual laughter presentation when compared with monomodal auditory or visual
      laughter cues. Considering the possibility to modulate cognitive biases and
      cerebral activity by neuropsychological trainings, non-invasive
      electrophysiological stimulation and psychotherapy, this study represents a
      starting point for a whole line of translational research projects and identifies
      promising targets for electrophysiological interventions aiming to alleviate
      cognitive biases and symptom severity in social anxiety. 

PMID- 24918627
TI  - Nurse moral distress and cancer pain management: an ethnography of oncology
      nurses in India.
AB  - BACKGROUND: The majority of cancer patients in low- and middle-income countries
      (LMICs) present with late-stage, incurable disease, and basic tools to alleviate
      patient suffering-such as morphine-are often absent. Oncology nurses must cope
      with many challenges and may experience moral distress (MD), yet little research
      has examined this experience in LMICs. OBJECTIVE: This ethnographic study
      explored the experience of MD with oncology nurses (n = 37) and other providers
      (n = 22) in India and its potential relationship to opioid availability. METHODS:
      Data (semistructured interviews and field observations) were collected at a 300
      bed government cancer hospital in urban South India over 9 months. Dedoose
      v.4.5.91 supported analysis of transcripts using a coding schema that mapped to
      an Integrated Model of Nurse Moral Distress and concepts that emerged from field
      notes. RESULTS: Primary themes included "We feel bad," "We are alone and afraid,"
      "We are helpless," and "We leave it." A weak link between MD and opioid
      availability was found. CONCLUSIONS: Participants described significant work
      related distress, but the moral dimension to this distress was less clear as some
      key aspects of the Integrated Model of Nurse Moral Distress were not supported.
      The concept of MD may have limited applicability in settings where alternative
      courses of action are unknown, or not feasible, and where differing social and
      cultural norms influence moral sensitivity. IMPLICATIONS FOR PRACTICE: Improving
      job-related conditions is prerequisite to creating an environment where MD can
      manifest. Educational initiatives in LMICs must account for the role of the
      oncology nurse and their contextual moral and professional obligations.

PMID- 24918626
TI  - The choice of regimens based on bortezomib for patients with newly diagnosed
      multiple myeloma.
AB  - INTRODUCTION: Bortezomib has significantly improved multiple myeloma (MM)
      response rates, but strategies for choosing bortezomib-based regimens for initial
      MM therapy are not standardized. Here, we describe four bortezomib-based
      therapies in Chinese MM patients to determine the optimal chemotherapeutic
      approach. METHODS: Newly diagnosed symptomatic MM patients at three hematological
      centers between February 1, 2006 and May 31, 2013 were treated with therapies
      including bortezomib plus dexamethasone (PD) or combinations of PD with either
      adriamycin (PAD), cyclophosphamide (PCD) or thalidomide (PTD) for every 28 days.
      RESULTS: The overall response rate of all the 215 eligible patients was 90.2%.
      The ORR for PCD, PAD, PTD and PD were 97.4%, 93.2%, 85.3% and 77.8% while the
      effects with VGPR or better were 63.7%, 62.7%, 44.2% and 37.8%, respectively. The
      effect of ORR, VGPR and CR/nCR for the PCD regimen was better than the PD
      protocol. Median PFS for all patients was 29.0 months with significant
      differences observed among treatment groups. Median OS of all the patients was
      not reached, but three-drug combinations were superior to PD alone. Frequently
      observed toxicities were neutropenia, thrombocytopenia, fatigue, infection,
      herpes zoster, and peripheral neuropathy. The incidence of peripheral neuropathy
      (PN) in PTD group was significantly higher than other three groups, especially
      grade 2-3 PN. Treatment with anti-viral agent acyclovir significantly reduced the
      incidence of herpes zoster. CONCLUSIONS: Our experience indicated that bortezomib
      based regimens were effective and well-tolerated in the Chinese population
      studied; three-drug combinations PCD, PAD were superior to PD, especially with
      respect to PCD.

PMID- 24918628
TI  - Enhanced photocatalytic CO2-reduction activity of anatase TiO2 by coexposed {001}
      and {101} facets.
AB  - Control of TiO2 crystal facets has attracted enormous interest due to the
      fascinating shape-dependent photocatalytic activity of this material. In this
      work, the effect of the ratio of {001} and {101} facets on the photocatalytic CO2
      reduction performance of anatase TiO2 is reported. A new "surface heterojunction"
      concept is proposed on the basis of the density functional theory (DFT)
      calculations to explain the difference in the photocatalytic activity of TiO2
      with coexposed {001} and {101} facets. 

PMID- 24918629
TI  - Exploring for the safer ventilation method in laparoscopic urologic patients?
      Conventional or low tidal?
AB  - BACKGROUND: To study the effects of low tidal volume with positive end-expiratory
      pressure (PEEP) on arterial blood gases of patients undergoing laparoscopic
      urologic surgeries. SUBJECTS AND METHODS: Eighty-six laparoscopic urologic
      patients were enrolled in this study. Patients were randomized into two groups
      according to the ventilatory settings. In the conventional group (Group C)
      (n=43), the tidal volume was 10 mL/kg, and the PEEP was set at 0 cm of H2O. In
      the low tidal volume with PEEP group (Group LP), the tidal volume was 6 mL/kg,
      with PEEP of 5 cm of H2O. In both groups total minute volume was 6 L/kg. Peak and
      plateau airway pressure (PPEAK and PPLAT, respectively) and arterial blood gases
      were recorded before pneumoperitoneum (PNP) (T1) and the first and third hour
      (T3) after PNP induction and also after extubation in the intensive care unit.
      Additionally, heart rate, mean arterial pressure, and peripheral O2 saturation of
      hemoglobin were recorded. RESULTS: Heart rate, PPEAK, and PPLAT values were
      similar in both groups. Partial arterial O2 pressure values measured
      postoperatively were significantly higher in Group LP, whereas those measured
      before PNP induction were similar (P=.014 and P=.056, respectively). Compared
      with the baseline, partial arterial CO2 pressure values measured at T1 and at T3
      after PNP induction were significantly higher in Group C than in Group LP
      (P<.001). The pH values of Group C at T1 and at T3 postoperatively were
      significantly lower than the values of Group LP (P<.001). Extubation times were
      significantly lower in Group LP. CONCLUSIONS: The results of the present study
      suggest that low tidal volume with PEEP application may be a good alternative for
      preventing high CO2 levels and yielding better oxygenation and lower extubation
      times in patients undergoing prolonged laparoscopic urology.

PMID- 24918630
TI  - Surfactant-induced phases in water-supported alkane monolayers: II. Structure.
AB  - The structure of the Langmuir-Gibbs films of normal alkanes C(n) of length n = 12
      21 formed at the surface of aqueous solutions of C(m)TAB surfactants, m = 14, 16,
      and 18, was studied by surface-specific synchrotron X-ray methods. At high
      temperatures, a laterally disordered monolayer of mixed alkane molecules and
      surface-adsorbed surfactant tails is found, having thicknesses well below those
      of the alkanes' and surfactant tails' extended length. The mixed monolayer
      undergoes a freezing transition at a temperature T(s)(n,m), which forms, for n <=
      m + 1, a crystalline monolayer of mixed alkane molecules and surfactant tails.
      For n >= m + 2, a bilayer forms, consisting of an upper pure-alkane, crystalline
      monolayer and a lower liquidlike monolayer. The crystalline monolayer in both
      cases consists of hexagonally packed extended, surface-normal-aligned chains. The
      hexagonal lattice constant is found to decrease with increasing n. The films'
      structure is discussed in conjunction with their thermodynamic properties
      presented in an accompanying paper.

PMID- 24918631
TI  - Contactless photoconductance study on undoped and doped nanocrystalline diamond
      films.
AB  - Hydrogen and oxygen surface-terminated nanocrystalline diamond (NCD) films are
      studied by the contactless time-resolved microwave conductivity (TRMC) technique
      and X-ray photoelectron spectroscopy (XPS). The optoelectronic properties of
      undoped NCD films are strongly affected by the type of surface termination. Upon
      changing the surface termination from oxygen to hydrogen, the TRMC signal rises
      dramatically. For an estimated quantum yield of 1 for sub-bandgap optical
      excitation the hole mobility of the hydrogen-terminated undoped NCD was found to
      be ~0.27 cm(2)/(V s) with a lifetime exceeding 1 MUs. Assuming a similar mobility
      for the oxygen-terminated undoped NCD a lifetime of ~100 ps was derived. Analysis
      of the valence band spectra obtained by XPS suggests that upon oxidation of
      undoped NCD the surface Fermi level shifts (toward an increased work function).
      This shift originates from the size and direction of the electronic dipole moment
      of the surface atoms, and leads to different types of band bending at the
      diamond/air interface in the presence of a water film. In the case of boron-doped
      NCD no shift of the work function is observed, which can be rationalized by
      pinning of the Fermi level. This is confirmed by TRMC results of boron-doped NCD,
      which show no dependency on the surface termination. We suggest that photoexcited
      electrons in boron-doped NCD occupy nonionized boron dopants, leaving relatively
      long-lived mobile holes in the valence band. 

PMID- 24918632
TI  - Complete wetting near an edge of a rectangular-shaped substrate.
AB  - We consider fluid adsorption near a rectangular edge of a solid substrate that
      interacts with the fluid atoms via long range (dispersion) forces. The curved
      geometry of the liquid-vapour interface dictates that the local height of the
      interface above the edge l(E) must remain finite at any subcritical temperature,
      even when a macroscopically thick film is formed far from the edge. Using an
      interfacial Hamiltonian theory and a more microscopic fundamental measure density
      functional theory (DFT), we study the complete wetting near a single edge and
      show that l(E)(0)-l(E)(deltaMU)~deltaMU(beta(CO)(E), as the chemical potential
      departure from the bulk coexistence deltaMU = MU(s)(T) - MU tends to zero. The
      exponent beta(CO)(E) depends on the range of the molecular forces and in
      particular beta(CO)(E)=2/3 for three-dimensional systems with van der Waals
      forces. We further show that for a substrate model that is characterised by a
      finite linear dimension L, the height of the interface deviates from the one at
      the infinite substrate as deltalE(L) ~ L(-1) in the limit of large L. Both
      predictions are supported by numerical solutions of the DFT.

PMID- 24918633
TI  - Chromatin properties of regulatory DNA probed by manipulation of transcription
      factors.
AB  - Transcription factors (TFs) bind to DNA and regulate the transcription of nearby
      genes. However, only a small fraction of TF binding sites have such regulatory
      effects. Here we search for the predictors of functional binding sites by
      carrying out a systematic computational screening of a variety of contextual
      factors (histone modifications, nuclear lamin-bindings, and cofactor bindings).
      We used regression analysis to test if contextual factors are associated with
      upregulation or downregulation of neighboring genes following the induction or
      knockdown of the 9 TFs in mouse embryonic stem (ES) cells. Functional TF binding
      sites appeared to be either active (i.e., bound by P300, CHD7, mediator, cohesin,
      and SWI/SNF) or repressed (i.e., with H3K27me3 histone marks and bound by
      Polycomb factors). Active binding sites mediated the downregulation of nearby
      genes upon knocking down the activating TFs or inducing repressors. Repressed TF
      binding sites mediated the upregulation of nearby genes (e.g., poised
      developmental regulators) upon inducing TFs. In addition, repressed binding sites
      mediated repressive effects of TFs, identified by the downregulation of target
      genes after the induction of TFs or by the upregulation of target genes after the
      knockdown of TFs. The contextual factors associated with functions of DNA-bound
      TFs were used to improve the identification of candidate target genes regulated
      by TFs.

PMID- 24918634
TI  - Youth risk behavior surveillance--United States, 2013.
AB  - PROBLEM: Priority health-risk behaviors contribute to the leading causes of
      morbidity and mortality among youth and adults. Population-based data on these
      behaviors at the national, state, and local levels can help monitor the
      effectiveness of public health interventions designed to protect and promote the
      health of youth nationwide. REPORTING PERIOD COVERED: September 2012-December
      2013. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System
      (YRBSS) monitors six categories of priority health-risk behaviors among youth and
      young adults: 1) behaviors that contribute to unintentional injuries and
      violence; 2) tobacco use; 3) alcohol and other drug use; 4) sexual behaviors that
      contribute to unintended pregnancy and sexually transmitted infections (STIs),
      including human immunodeficiency virus (HIV) infection; 5) unhealthy dietary
      behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence
      of obesity and asthma. YRBSS includes a national school-based Youth Risk Behavior
      Survey (YRBS) conducted by CDC and state and large urban school district school
      based YRBSs conducted by state and local education and health agencies. This
      report summarizes results for 104 health-risk behaviors plus obesity, overweight,
      and asthma from the 2013 national survey, 42 state surveys, and 21 large urban
      school district surveys conducted among students in grades 9-12. RESULTS: Results
      from the 2013 national YRBS indicated that many high school students are engaged
      in priority health-risk behaviors associated with the leading causes of death
      among persons aged 10-24 years in the United States. During the 30 days before
      the survey, 41.4% of high school students nationwide among the 64.7% who drove a
      car or other vehicle during the 30 days before the survey had texted or e-mailed
      while driving, 34.9% had drunk alcohol, and 23.4% had used marijuana. During the
      12 months before the survey, 14.8% had been electronically bullied, 19.6% had
      been bullied on school property, and 8.0% had attempted suicide. Many high school
      students nationwide are engaged in sexual risk behaviors that contribute to
      unintended pregnancies and STIs, including HIV infection. Nearly half (46.8%) of
      students had ever had sexual intercourse, 34.0% had had sexual intercourse during
      the 3 months before the survey (i.e., currently sexually active), and 15.0% had
      had sexual intercourse with four or more persons during their life. Among
      currently sexually active students, 59.1% had used a condom during their last
      sexual intercourse. Results from the 2013 national YRBS also indicate many high
      school students are engaged in behaviors associated with chronic diseases, such
      as cardiovascular disease, cancer, and diabetes. During the 30 days before the
      survey, 15.7% of high school students had smoked cigarettes and 8.8% had used
      smokeless tobacco. During the 7 days before the survey, 5.0% of high school
      students had not eaten fruit or drunk 100% fruit juices and 6.6% had not eaten
      vegetables. More than one-third (41.3%) had played video or computer games or
      used a computer for something that was not school work for 3 or more hours per
      day on an average school day. INTERPRETATION: Many high school students engage in
      behaviors that place them at risk for the leading causes of morbidity and
      mortality. The prevalence of most health-risk behaviors varies by sex,
      race/ethnicity, and grade and across states and large urban school districts.
      Long term temporal changes also have occurred. Since the earliest year of data
      collection, the prevalence of most health-risk behaviors has decreased (e.g.,
      physical fighting, current cigarette use, and current sexual activity), but the
      prevalence of other health-risk behaviors has not changed (e.g., suicide attempts
      treated by a doctor or nurse, having ever used marijuana, and having drunk
      alcohol or used drugs before last sexual intercourse) or has increased (e.g.,
      having not gone to school because of safety concern and obesity and overweight).
      PUBLIC HEALTH ACTION: YRBSS data are used widely to compare the prevalence of
      health-risk behaviors among subpopulations of students; assess trends in health
      risk behaviors over time; monitor progress toward achieving 20 national health
      objectives for Healthy People 2020 and one of the 26 leading health indicators;
      provide comparable state and large urban school district data; and help develop
      and evaluate school and community policies, programs, and practices designed to
      decrease health-risk behaviors and improve health outcomes among youth.

PMID- 24918636
TI  - Metabolomics of human brain aging and age-related neurodegenerative diseases.
AB  - Neurons in the mature human central nervous system (CNS) perform a wide range of
      motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse
      functional output requires a great diversity of CNS neuronal and non-neuronal
      populations. Metabolomics encompasses the study of the complete set of
      metabolites/low-molecular-weight intermediates (metabolome), which are context
      dependent and vary according to the physiology, developmental state, or
      pathologic state of the cell, tissue, organ, or organism. Therefore, the use of
      metabolomics can help to unravel the diversity-and to disclose the specificity-of
      metabolic traits and their alterations in the brain and in fluids such as
      cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of
      aging and neurodegenerative diseases. Here, we review the current applications of
      metabolomics in studies of CNS aging and certain age-related neurodegenerative
      diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral
      sclerosis. Neurometabolomics will increase knowledge of the physiologic and
      pathologic functions of neural cells and will place the concept of selective
      neuronal vulnerability in a metabolic context. 

PMID- 24918635
TI  - Involvement of matrix metalloproteinase-9 in amyloid-beta 1-42-induced shedding
      of the pericyte proteoglycan NG2.
AB  - Deposition of amyloid-beta (Abeta) 1-42, the major component of senile plaques
      characteristic of Alzheimer disease, affects brain microvascular integrity and
      causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte
      degeneration. To understand the cellular events underlying Abeta1-42 effects on
      microvascular alterations, we investigated whether different aggregation forms of
      Abeta1-42 affect shedding of the pericyte proteoglycan NG2 and whether they
      affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We
      found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in
      pericyte culture supernatants in response to fibril-enriched preparations of
      Abeta1-42. Conversely, oligomer-enriched preparations of Abeta1-42 increased
      soluble NG2 levels in the supernatants. This increase was ablated by the MMP
      9/MMP-2 inhibitor SB-3CT. There was also a trend toward increased MMP-9 activity
      observed after oligomeric Abeta1-42 exposure. Our results, demonstrating an
      Abeta1-42 aggregation-dependent effect on levels of NG2 and MMP-9, support
      previous studies showing an impact of Abeta1-42 on vascular integrity and thereby
      add to our understanding of mechanisms behind the microvascular changes commonly
      found in patients with Alzheimer disease. 

PMID- 24918637
TI  - Immunostaining of oxidized DJ-1 in human and mouse brains.
AB  - DJ-1, the product of a causative gene of a familial form of Parkinson disease,
      undergoes preferential oxidation of Cys106 (cysteine residue at position 106)
      under oxidative stress. Using specific monoclonal antibodies against Cys106
      oxidized DJ-1 (oxDJ-1), we examined oxDJ-1 immunoreactivity in brain sections
      from DJ-1 knockout and wild-type mice and in human brain sections from cases
      classified into different Lewy body stages of Parkinson disease and Parkinson
      disease with dementia. Oxidized DJ-1 immunoreactivity was prominently observed in
      neuromelanin-containing neurons and neuron processes of the substantia nigra;
      Lewy bodies also showed oxDJ-1 immunoreactivity. Oxidized DJ-1 was also detected
      in astrocytes in the striatum, in neurons and glia in the red nucleus, and in the
      inferior olivary nucleus, all of which are related to regulation of movement.
      These observations suggest the relevance of DJ-1 oxidation to homeostasis in
      multiple brain regions, including neuromelanin-containing neurons of the
      substantia nigra, and raise the possibility that oxDJ-1 levels might change
      during the progression of Lewy body-associated neurodegenerative diseases. 

PMID- 24918638
TI  - Semaphorin 3A signaling through neuropilin-1 is an early trigger for distal
      axonopathy in the SOD1G93A mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by
      progressive distal axonopathy that precedes actual motor neuron death. Triggers
      for neuromuscular junction degeneration remain to be determined, but the axon
      repulsion factor semaphorin 3A (Sema3A), which is derived from terminal Schwann
      cells, is a plausible candidate. This study examines the hypothesis that Sema3A
      signaling through its motor neuron neuropilin-1 (NRP1) receptor triggers distal
      axonopathy and muscle denervation in the SOD1 mouse model of ALS. Neuropilin-1
      was found to be expressed in axonal terminals at the mouse neuromuscular junction
      in vivo and in NSC-34 motor neuron-like cells in vitro. In differentiated NSC-34
      cells, an anti-NRP1 antibody that selectively blocks Sema3A binding to NRP1
      prevented Sema3A-induced growth cone collapse. Furthermore, intraperitoneal
      injections of anti-NRP1 antibody administered twice weekly from age 40 days
      significantly delayed and even temporarily reversed motor functional decline
      while prolonging the life span of SOD1 mice. Histologic evaluation at 90 and 125
      days revealed that anti-NRP1 antibody reduced neuromuscular junction denervation
      and attenuated pathologic alterations in ventral roots at late-stage disease.
      These data suggest that peripheral NRP1 signaling is involved in the pathobiology
      of this ALS model and that antagonizing Sema3A/NRP1 binding or downstream signals
      could have implications for the treatment of ALS. 

PMID- 24918639
TI  - mTOR Hyperactivation in down syndrome hippocampus appears early during
      development.
AB  - The mammalian target of rapamycin (mTOR) signaling pathway is a key developmental
      pathway involved in mechanisms underlying cellular aging and neurodegeneration.
      We hypothesized that its deregulation may occur during early brain development in
      patients with Down syndrome (DS). The expression patterns and cellular
      distribution of components of mTOR signaling (phosphorylated S6, phosphorylated
      S6 kinase, phosphorylated eukaryotic initiation factor 4E binding protein 1, and
      phosphorylated mTOR) were investigated in developing hippocampi from controls and
      patients with DS and from adults with DS and Alzheimer disease-associated
      pathology using immunocytochemistry. In control hippocampi, only phosphorylated
      S6 was detected prenatally (19-41 gestational weeks); it became undetectable 2
      months postnatally. Increased expression of phosphorylated S6, phosphorylated S6
      kinase, phosphorylated eukaryotic initiation factor 4E binding protein 1, and
      phosphorylated mTOR was observed in DS hippocampus compared with controls.
      Phosphorylated S6 and phosphorylated S6 kinase were detected prenatally and
      persisted throughout postnatal development. Prominent expression of mTOR
      components was observed in pyramidal neurons with granulovacuolar degeneration
      and in neurons containing neurofibrillary tangles in the hippocampi of DS
      subjects with Alzheimer disease pathology. These findings suggest that a
      dysregulated mTOR pathway may contribute to both early hippocampal developmental
      abnormalities and hippocampal functional impairment developing before
      neurodegeneration. Moreover, the expression patterns of mTOR components in adult
      DS hippocampus support its association with Alzheimer disease-related
      histopathologic changes. 

PMID- 24918640
TI  - Defining peripheral nervous system dysfunction in the SOD-1G93A transgenic rat
      model of amyotrophic lateral sclerosis.
AB  - Growing evidence indicates that alterations within the peripheral nervous system
      (PNS) are involved at an early stage in the amyotrophic lateral sclerosis (ALS)
      pathogenetic cascade. In this study, magnetic resonance imaging (MRI),
      neurophysiologic analyses, and histologic analyses were used to monitor the
      extent of PNS damage in the hSOD-1 ALS rat model. The imaging signature of the
      disease was defined using in vivo MRI of the sciatic nerve. Initial abnormalities
      were detected in the nerves by an increase in T2 relaxation time before the onset
      of clinical disease; diffusion MRI showed a progressive increase in mean and
      radial diffusivity and reduction of fractional anisotropy at advanced stages of
      disease. Histologic analysis demonstrated early impairment of the blood-nerve
      barrier followed by acute axonal degeneration associated with endoneurial edema
      and macrophage response in motor nerve compartments. Progressive axonal
      degeneration and motor nerve fiber loss correlated with MRI and neurophysiologic
      changes. These functional and morphologic investigations of the PNS might be
      applied in following disease progression in preclinical therapeutic studies. This
      study establishes the PNS signature in this rat ALS model (shedding new light
      into pathogenesis) and provides a rationale for translating into future
      systematic MRI studies of PNS involvement in patients with ALS. 

PMID- 24918642
TI  - Epstein-barr virus in the central nervous system and cervical lymph node of a
      patient with primary progressive multiple sclerosis.

PMID- 24918641
TI  - Lack of neuropathy-related phenotypes in hint1 knockout mice.
AB  - Mutations in HINT1, the gene encoding histidine triad nucleotide-binding protein
      1 (HINT1), cause a recessively inherited peripheral neuropathy that primarily
      involves motor dysfunction and is usually associated with neuromyotonia (i.e.
      prolonged muscle contraction resulting from hyperexcitability of peripheral
      nerves). Because these mutations are hypothesized to cause loss of function, we
      analyzed Hint1 knockout mice for their relevance as a disease model. Mice lacking
      Hint1 appeared normal and yielded normal behavioral test results or motor
      performance, although they moved more slowly and for a smaller fraction of time
      in an open-field arena than wild-type mice. Muscles, neuromuscular junctions, and
      nodes of Ranvier were anatomically normal and did not show evidence of
      degeneration or regeneration. Axon numbers and myelination in peripheral nerves
      were normal at ages 4 and 13 months. Axons were slightly smaller than those in
      wild-type mice at age 4 months, but this did not cause a decrease in conduction
      velocity, and no differences in axon diameters were detected at 13 months. With
      electromyography, we were unable to detect neuromyotonia even after using
      supraphysiologic stimuli and stressors such as reduced temperature or 3,4
      diaminopyridine to block potassium channels. Therefore, we conclude that Hint1
      knockout mice may be useful for studying the biochemical activities of HINT1, but
      these mice do not provide a disease model or a means for investigating the basis
      of HINT1-associated neuropathy and neuromyotonia. 

PMID- 24918643
TI  - Do older adults' beliefs about their community mobility predict walking
      performance?
AB  - Among older adults, preserving community mobility (CM) is important for
      maintaining independent living. We explored whether perceptions of the
      environment and self-efficacy for CM (SE-CM) would predict walking performance
      for tasks reflecting CM. We hypothesized that perceptions of the environment and
      SE-CM would be additive predictors of walking performance on tasks reflecting the
      complexity of CM. Independent living older adults (N = 60) aged 64-85 completed
      six complex walking tasks (CWTs), SE-CM, and the environmental analysis of
      mobility questionnaire (EAMQ). Multiple regression analyses indicated that for
      each CWT, the EAMQ scales predicted walking performance (range: model R2Adj. =
      .078 to .139, p < .04). However, when SE-CM was added to the models, it was the
      sole significant predictor (p < .05). Contrary to our hypotheses, SE-CM was the
      best predictor in the additive models. SE-CM may be more correspondent to walking
      tests and thus a more sensitive predictor of CM walking performance. 

PMID- 24918645
TI  - Dulaglutide for the treatment of type 2 diabetes.
AB  - Dulaglutide is a novel glucagon-like peptide 1 (GLP-1) receptor agonist with a
      unique structure that supports once-weekly dosing in patients with type 2
      diabetes (T2DM), most of whom have a big pill burden. It appears to be
      efficacious in reducing hemoglobin A1c (HbA1c) up to 1.59% and promotes modest
      weight loss up to 3 kg with a low incidence of hypoglycemia and mild to moderate
      gastrointestinal adverse events. Convenient weekly dosing could improve
      compliance and help attain sustained glycemic goals. Addressing obesity is an
      integral part of T2DM management and weight loss may contribute to better
      glycemic and cardiovascular benefits. Results of ongoing clinical trials on
      cardiovascular safety are important to determine the risk-to-benefit ratio. As
      with any drug, patient selection and ongoing monitoring will be important. If
      approved, dulaglutide will be one of the first weekly GLP-1 receptor agonist to
      be available in a ready-to-use pen device with an automatic injector. 

PMID- 24918646
TI  - Ibrutinib for the treatment of chronic lymphocytic leukemia and mantle cell
      lymphoma.
AB  - Ibrutinib is a novel oral tyrosine kinase inhibitor that irreversibly binds and
      inhibits tyrosine-protein kinase BTK (Bruton tyrosine kinase). BTK has been found
      to be important in the function of B-cell receptor signaling and therefore in the
      maintenance and expansion of various B-cell malignancies including chronic
      lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Targeting BTK with
      ibrutinib has been found to be an effective strategy in treating these
      malignancies. Phase I clinical testing in non-Hodgkin's lymphomas and CLL showed
      that the drug was extremely well tolerated with no major dose-limiting toxicities
      and a 54% overall response rate. Subsequently, two phase Ib/II studies were
      performed on patients with CLL, one in relapsed/refractory CLL and one in
      previously untreated elderly patients with CLL. Both of these studies continued
      to show good tolerability of the drug and an overall response rate of about 71%
      with extended duration of response. Another phase II study using ibrutinib in
      relapsed/refractory MCL was conducted and also showed that it was well tolerated
      with an overall response rate of 68% and extended duration of response. Due to
      these results, the U.S. Food and Drug Administration granted accelerated approval
      for ibrutinib in November 2013 for patients with MCL who had received at least
      one prior therapy and in February 2014 for patients with CLL who had received at
      least one prior therapy. This review will discuss the preclinical pharmacology,
      pharmacokinetics and clinical efficacy to date of ibrutinib in the treatment of
      CLL and MCL. 

PMID- 24918644
TI  - Effect of high-dose irradiation on human bone-marrow-derived mesenchymal stromal
      cells.
AB  - Cell therapy using multipotent mesenchymal stromal cells (MSCs) is of high
      interest in various indications. As the pleiotropic effects mediated by MSCs rely
      mostly on their unique secretory profile, long-term persistence of ex-vivo
      expanded cells in the recipient may not always be desirable. Irradiation is a
      routine procedure in transfusion medicine to prevent long-term persistence of
      nucleated cells and could therefore also be applied to MSCs. We have exposed
      human bone-marrow-derived MSCs to 30 or 60 Gy of gamma-irradiation and assessed
      cell proliferation, clonogenicity, differentiation, cytokine levels in media
      supernatants, surface receptor profile, as well as expression of proto
      oncogenes/cell cycle markers, self-renewal/stemness markers, and DNA
      damage/irradiation markers. Irradiated MSCs show a significant decrease in
      proliferation and colony-forming unit-fibroblasts. However, a subpopulation of
      surviving cells is able to differentiate, but is unable to form colonies after
      irradiation. Irradiated MSCs showed stable expression of CD73 and CD90 and
      absence of CD3, CD34, and CD45 during a 16-week follow-up period. We found
      increased vascular endothelial growth factor (VEGF) levels and a decrease of
      platelet-derived growth factor (PDGF)-AA and PDGF-AB/BB in culture media of
      nonirradiated cells. Irradiated MSCs showed an inverse pattern, that is, no
      increase of VEGF, and less consumption of PDGF-AA and PDGF-AB/BB. Interestingly,
      interleukin-6 (IL-6) levels increased during culture regardless of irradiation.
      Cells with lower sensitivity toward gamma-irradiation showed positive beta
      galactosidase activity 10 days after irradiation. Gene expression of both
      irradiated and nonirradiated MSCs 13-16 weeks after irradiation with 60 Gy
      predominantly followed the same pattern; cell cycle regulators CDKN1A (p21) and
      CDKN2A (p16) were upregulated, indicating cell cycle arrest, whereas classical
      proto-oncogenes, respectively, and self-renewal/stemness markers MYC, TP53 (p53),
      and KLF4 were downregulated. In addition, DNA damage/irradiation markers ATM,
      ATR, BRCA1, CHEK1, CHEK2, MDC1, and TP53BP1 also mostly showed the same pattern
      of gene expression as high-dose gamma-irradiation. In conclusion, we demonstrated
      the existence of an MSC subpopulation with remarkable resistance to high-dose
      gamma-irradiation. Cells surviving irradiation retained their trilineage
      differentiation capacity and surface marker profile but changed their cytokine
      secretion profile and became prematurely senescent. 

PMID- 24918647
TI  - Racotumomab - a novel anti-idiotype monoclonal antibody vaccine for the treatment
      of cancer.
AB  - Racotumomab is a murine gamma-type anti-idiotype monoclonal antibody that
      specifically induces an antibody response against Neu-glycolyl GM3 ganglioside
      (NeuGcGM3), which is overexpressed in several solid tumors. It is adjuvanted with
      aluminum hydroxide for intradermal administration as a cancer vaccine
      (racotumomab-Alum, known commercially as Vaxira(r)). Racotumomab is currently
      being evaluated for a number of cancer indications, including melanoma, breast
      and lung cancer. In early clinical trials, racotumomab demonstrated high
      immunogenicity and low toxicity and it advanced to further clinical testing as a
      treatment for patients with non-small cell lung cancer (NSCLC). On the basis of
      promising results in a phase II/III study, racotumomab was launched in 2013 in
      Cuba and Argentina as an intradermal injection for the treatment of patients with
      advanced stage NSCLC. 

PMID- 24918648
TI  - Vedolizumab for the treatment of inflammatory bowel disease.
AB  - The causes of inflammatory bowel diseases, such as ulcerative colitis (UC) and
      Crohn's disease (CD), remain to be elucidated. However, characteristic
      inflammation of the gastrointestinal mucosa is caused by infiltration of T
      lymphocytes into the submucosal layer. Inhibiting this immune response is a
      promising therapeutic target. Integrins expressed on the cell surface mediate gut
      homing of T lymphocytes. Blockade of integrin-cell adhesion molecule interaction
      using antibodies against alpha4-containing integrins, namely natalizumab, has
      shown clinical efficacy; however, this drug's lack of alpha4-containing integrin
      specificity leads to systemic immunosuppression that caused progressive
      multifocal leukoencephalopathy and death in some patients resulting in its
      withdrawal from the market. Vedolizumab specifically targets the alpha4beta7
      integrin that is selectively expressed on gut-homing T lymphocytes. Vedolizumab
      successfully extended clinical remission in patients with UC or CD and reduced
      patient reliance on corticosteroid use. The drug is well tolerated and there have
      been no deaths or reports of progressive multifocal leukoencephalopathy infection
      in patients receiving vedolizumab. A phase III long-term 7-year safety study in
      patients with UC and CD is under way. Regulatory applications are under review in
      the U.S. and E.U. for its use in the treatment of patients with UC and CD, with
      decisions expected in mid-2014.

PMID- 24918649
TI  - A report from the 72nd annual meeting of the American Academy of Dermatology
      (March 21-25 - Denver, Colorado, USA).
AB  - March, at 5,000 feet above sea level, is not the best season for having much skin
      exposed, particularly when snow flurries are coming down on one's face. However,
      that was the time and place for sharing or getting new knowledge of skin science
      during this year's annual meeting of the American Academy of Dermatology. At high
      altitude, a high level of science was constant throughout the meeting sessions,
      including, notably, the Latest in Dermatology Research symposium held on Saturday
      March 22, and the electronic poster presentations available to attendees
      throughout the conference. This report summarizes the most significant new
      scientific findings reported during the meeting, which have a direct impact on
      how diseases of the skin are or will possibly be treated in the foreseen future. 

PMID- 24918650
TI  - Atomic force microscopic detection enabling multiplexed low-cycle-number
      quantitative polymerase chain reaction for biomarker assays.
AB  - Quantitative polymerase chain reaction is the current "golden standard" for
      quantification of nucleic acids; however, its utility is constrained by an
      inability to easily and reliably detect multiple targets in a single reaction. We
      have successfully overcome this problem with a novel combination of two widely
      used approaches: target-specific multiplex amplification with 15 cycles of
      polymerase chain reaction (PCR), followed by single-molecule detection of
      amplicons with atomic force microscopy (AFM). In test experiments comparing the
      relative expression of ten transcripts in two different human total RNA samples,
      we find good agreement between our single reaction, multiplexed PCR/AFM data, and
      data from 20 individual singleplex quantitative PCR reactions. This technique can
      be applied to virtually any analytical problem requiring sensitive measurement
      concentrations of multiple nucleic acid targets. 

PMID- 24918651
TI  - [Influence of polymer type on the physical properties and the release study of
      papaverine hydrochloride from tablets].
AB  - BACKGROUND: Polymers are widely used in drug manufacturing. Researchers studied
      their impact on the bioavailability of active substances or on physical
      properties of tablets for many years. OBJECTIVES: To study the influence of
      polymer excipients, such as microcrystalline cellulose (Avicel PH 101, Avicel PH
      102), croscarmellose sodium, crospovidone or polyvinylpyrrolidone, on the release
      profile of papaverine hydrochloride from tablets and on the physical properties
      of tablets. MATERIAL AND METHODS: Six series of uncoated tablets were prepared by
      indirect method, with previous wet granulation. Tablets contained papaverine
      hydrochloride and various excipients. The physical properties of the prepared
      granules, tablets and the release profile of papaverine hydrochloride from
      tablets were examined. The content of papaverine hydrochloride from the release
      study were determined spectrophotometrically. RESULTS: All tablets met the
      pharmacopoeia requirements during following tests: the disintegration time of
      tablets, uncoated tablets resistance to abrasion, the weight uniformity and dose
      formulations, their dimensions, the resistance to crushing of tablets and the
      drug substance content in the tablet. In four cases more than 80% of papaverine
      was released up to 2 min, in one formula it was up to 5 min, and in last one up
      to 10 min. CONCLUSIONS: Tablets containing crospovidone disintegrated faster than
      tablets with croscarmellose sodium. Adding gelatinized starch to the tablet
      composition increased the disintegration time, hardness and delayed the release
      of papaverine. During the wet granulation process, granules containing
      polyvinylpyrrolidone were characterized by a suitable flow properties and
      slightly prolonged disintegration time. Tablets containing Avicel PH 102 compared
      to tablets with Avicel PH 101 had less weight loss during the test of mechanical
      resistance, improved hardness and faster release profile of papaverine from
      tablets.

PMID- 24918652
TI  - [Influence of primers ' chemical composition on shear bond strength of resin
      cement to zirconia ceramic].
AB  - BACKGROUND: Resin cements establish a strong durable bond between zirconia
      ceramic and hard tissues of teeth. It is essential to use primers with proper
      chemical composition before cementation. OBJECTIVES: The aim of this study was to
      assess the influence of primer's chemical composition on the shear bond strength
      of zirconia ceramic to resin cements. MATERIAL AND METHODS: 132 zirconia
      specimens were randomly assigned to four groups. There were four resin systems
      used. They included resin cement and respective primer, dedicated to zirconia:
      Clearfil Ceramic Primer/Panavia F2.0, Monobond Plus/Multilink Automix, AZ -
      Primer/ResiCem, Z - Prime Plus/Duo-Link. In each group the protocol of
      cementation was as follows: application of primer to the zirconia surface and
      application of the respective resin cement in cylindric mold (dimensions: 3.0 mm
      height and 3.0 mm diameter). Then, the shear bond strength was evaluated and the
      failure type was assessed in lupes (*2.5 magnification), also random specimens
      under SEM. The Wilcoxon test was used to analyze the data, the level of
      significance was alpha = 0.05. Finally, the known chemical composition of each
      primer was analysed in reference to probable chemical bonds, which may occure
      between primers and zirconia. RESULTS: The mean shear bond strength between resin
      cements and zirconia was the highest for Z-Prime Plus/Duo-Link (8.24 +/- 3,21
      MPa) and lowest for Clearfil Ceramic Primer/Panavia F 2.0 (4.60 +/- 2.21 MPa).
      The analysis revealed significant difference between all groups, except pair
      Clearfil Ceramic Primer/Panavia F 2.0 and AZ-Primer/ResiCem. The failure type in
      groups of Clearfil Ceramic Primer/Panavia F 2.0 and AZ-Primer/ResiCem was mainly
      adhesive, in groups Monobond Plus/ /Multilink Automix and Z-Prime Plus/Duo-Link
      mainly mixed. The chemical composition of primers affects different bond
      mechanisms between resin cements and zirconia. CONCLUSIONS: The highest shear
      bond strength of resin cement to zirconia can be obtained for the primer composed
      of 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) and carboxylic monomer -
      Biphenyl dimethacrylate (BPDM).

PMID- 24918653
TI  - Ageing phenomenon in acrylic polymer dental materials detected by means of
      positron annihilation lifetime spectroscopy.
AB  - BACKGROUND: Polymer materials based on acrylic monomers are commonly used in
      dentistry. It is important to research the structure of dental filling materials
      towards the material ageing. OBJECTIVES: The study has been conducted in order to
      determine the presence of free volume gaps in the structure of polymer materials.
      MATERIAL AND METHODS: Brand new, acrylic polymer based samples of dental Dipol
      materials were used as a research material. The study was conducted by means of
      the positron annihilation lifetime spectroscopy (PALS). RESULTS: As a result of
      the conducted measurements, curves describing numbers of counts of the acts of
      annihilation in the time function were obtained. The conducted studies revealed
      the existence of four components tau1, tau2, tau3 and tau4. The tau3 and tau4
      components are attributed to the pick-off annihilation of o-Ps orthopositronium
      trapping by free volume gaps and provide information about geometrical parameters
      of the volumes. LT 9 computer program was used to calculate components. Free
      volume holes were determined from empirical relationship between the radius of
      free volume and the long lifetime components. CONCLUSIONS: Conducted studies
      indicate the presence of free volume holes in the research materials. It has been
      noted that a new long lifetime component is assigned to a new kind of free
      volumes that exist in the structure of material related to the material ageing.

PMID- 24918654
TI  - [The use of contact angle and the surface free energy as the surface
      characteristics of the polymers used in medicine].
AB  - BACKGROUND: In the interaction process between implant and a living organism an
      important role is covered by the material layer. Many studies in the field of
      chemical engineering concern biomaterials surface. OBJECTIVES: Changes estimation
      of properties of polymers surface layer due to hydrolytic degradation on the base
      on measurements of contact angles and calculation of the surface free energy.
      MATERIAL AND METHODS: Contact angle measurements were made for the two polymers:
      polylactide (PLA) and polyhydroxyalkanoate (PHA) undergoing the hydrolytic
      degradation process over a period of 27 months. Based on the measured values of
      contact angles, surface free energy by the Owens-Wendt method and the critical
      surface tension were calculated. RESULTS: The surface for both tested polymers is
      hydrophilic. Hydrolytic degradation influences the growth of the surface free
      energy and the critical surface tension. CONCLUSIONS: Methodology can be a easily
      available for the initial assessment of the material from the point of view of
      the ability to cell adhesion and the progress of the degradation process.

PMID- 24918655
TI  - [Network form of the Kedem-Katchalsky equations for ternary non-electrolyte
      solutions 7. Evaluation of Sij Peusner's coefficients for polymeric membrane].
AB  - BACKGROUND: Peusner's network thermodynamics (PNT) allows symmetrical and/or
      hybrid transformation of Kedem-Katchalsky (K-K) equations to network form. For
      homogenous solutions that consist of solvent and two soluble nonelec-metrolyte
      substances, there are two symmetrical and six hybrid forms of network K-K
      equations that contain symmetrical (Rij or Lij) or hybrid (Hij, Wij, Sij, Nij,
      Kij or Pij) Peusner coefficients. OBJECTIVES: The aim of this study is to
      introduce the hybrid form of network K-K equations that include tensor Peusner
      coefficients Sij (i, j ? {1, 2, 3}) for homogenous ternary solutions of
      nonelectrolytes and to calculate dependences of coefficients Sij on mean
      concentration of one solution component (C1) when the concentration of the other
      one is constant (C2). MATERIAL AND METHODS: The authors used celulose Nephrophan
      membrane of known transport parameters for aqueous glucose and ethanol solutions
      as a study material. The authors applied PNT formalism and K-K equations for
      ternary nonelectrotyle solutions as a study method. RESULTS: Hybrid network form
      of K-K equations was obtained for solutions that consist of a solvent and two
      dissolved non-electrolyte substances. Dependences of coefficients Sij (i, j ? {1,
      2, 3}) on mean concentration of one solution component (C1) when the
      concentration of the other one is constant C2, were calculated for conditions of
      homogeneity of solutions. These calculations were done using experimentally
      determined coefficients of reflection (sigma), hydraulic (Lp) and solute
      permeability (omega). CONCLUSIONS: Network form of K-K equations that include
      Peusner coefficients Sij (i, j ? {1, 2, 3}) constitutes a novel research tool to
      study membrane transport. We showed that coefficients S11, S12, S13, S21, S22,
      S23, S31, S32 and S33 were sensitive to alterations in concentration and
      composition of solutions separated by a polymer membrane.

PMID- 24918656
TI  - [Perspectives of use of polymer carriers of epidoxorubicin and cyclophosphamide
      in cancer therapy].
AB  - Cancer diseases are an important problem of the contemporary clinical medicine
      and pharmacology. Chemotherapy using cytostatic drugs has developed in the last
      30 years. At present, it is the main method of therapy of metastatic cancers.
      Cytostatics have an important role in the cancer therapy. They have particular
      meaning in the therapy of solid and hematological tumors. However, using
      cytostatic drugs is limited due to their toxic effects on healthy cells. In last
      years, the decrease of toxicity of cytostatic drugs and the increase of their
      therapeutic properties are intensively investigated. In this paper, the polymer
      carriers of cytostatic drugs (mainly epirubicin and cyclophosphamide) and
      examples of their applications were described. 

PMID- 24918657
TI  - Narcissism and Internet pornography use.
AB  - This study examined the relation between Internet pornography use and narcissism.
      Participants (N=257) completed an online survey that included questions on
      Internet pornography use and 3 narcissism measures (i.e., Narcissistic
      Personality Inventory, Pathological Narcissistic Inventory, and the Index of
      Sexual Narcissism). The hours spent viewing Internet pornography was positively
      correlated to participants' narcissism level. In addition, those who have ever
      used Internet pornography endorsed higher levels of all 3 measures of narcissism
      than did those who have never used Internet pornography. 

PMID- 24918658
TI  - Development and validation of a quantitative real-time polymerase chain reaction
      assay specific for the detection of Rickettsia felis and not Rickettsia felis
      like organisms.
AB  - Human infections with Rickettsia felis have been reported worldwide. Recent
      studies have revealed the presence of many closely related but unique
      rickettsiae, referred to as Rickettsia felis-like organisms (RFLO), identified in
      various arthropods. Due to the recent discovery of the lack of specificity of
      earlier R. felis-specific assays, there has become a need to develop a new
      generation of R. felis-specific molecular assays that will differentiate R. felis
      not only from other rickettsiae but more importantly from other members of the R.
      felis genogroup that may not be pathogenic to humans. This new generation of
      assays is essential for determining the true risk for flea-borne spotted fever
      (FBSF) by surveying arthropod vectors/hosts. Because of the lack of specificity
      of previous assays developed to detect R. felis infections, prior surveys may
      have overestimated the prevalence of R. felis in arthropod vectors and thus the
      perceived risk of FBSF. We have developed a specific quantitative real-time
      polymerase chain reaction (qPCR) assay to detect R. felis (RfelB). Specificity of
      the assay was determined by testing it with a panel of 17 related Rickettsia
      species and 12 nonrickettsial bacterial DNA preparations. The RfelB qPCR assay
      was positive for R. felis DNA and negative for all of the 17 related Rickettsia
      species and 12 nonrickettsia bacterial DNA preparations. The limit of detection
      of the RfelB qPCR assay was determined to be two copies (two genoequivalents) per
      microliter of R. felis target ompB fragment-containing plasmid. Validation of the
      RfelB qPCR assay was accomplished by testing 83 previously sequence-confirmed R.
      felis and RFLOs containing DNA preparations from human and flea samples collected
      from different geographical locations around the world. This assay will be useful
      for rapid detection, identification, and enumeration of R. felis, an emerging
      human pathogen of worldwide importance, from both clinical and environmental
      samples.

PMID- 24918659
TI  - Plasmonic quasicrystals with broadband transmission enhancement.
AB  - Plasmonic quasicrystals (PlQCs), by integrating the properties of quasicrystals
      (rotational symmetry and long range ordering but lack translational symmetry) and
      surface plasmon polariton mediated effects, offer several advantages over
      plasmonic crystals (PlCs). For example, in PlQCs one could have broadband,
      polarization independent response. However, large area patterning by electron
      beam lithography requires precise lattice coordinates as well as a practical way
      to design the structures for specific spectral response. We demonstrate design
      and fabrication of large area quasicrystal air hole patterns of pi/5 symmetry in
      metal film in which broadband, polarization and launch angle independent
      transmission enhancement is observed. We demonstrate bi-grating quasicrystals to
      show that designable transmission response is possible over visible to near
      infrared wavelength regions with about 15 times enhancement. These would be
      useful in many applications like energy harvesting, nonlinear optics and quantum
      plasmonics. 

PMID- 24918660
TI  - Efficiency of class I and class II malocclusion treatment with four premolar
      extractions.
AB  - Four premolar extractions is a successful protocol to treat Class I malocclusion,
      but it is a less efficient way when compared with other Class II treatment
      protocols. OBJECTIVE: The objective of this study was to evaluate the influence
      of anteroposterior discrepancy on the success of four premolar extractions
      protocol. For that, treatment efficiency of Class I and complete Class II
      malocclusions, treated with four premolar extractions were compared. METHODS: A
      sample of 107 records from 75 Class I (mean age of 13.98 years--group 1) and 32
      Class II (mean age of 13.19 years--group 2) malocclusion patients treated with
      four premolar extractions was selected. The initial and final occlusal status of
      each patient was evaluated on dental casts with the PAR index. The treatment time
      was calculated based on the clinical charts, and the treatment efficiency was
      obtained by the ratio between the percentage of PAR reduction and treatment time.
      The PAR index and its components, the treatment time and the treatment efficiency
      of the groups were statistically compared with t tests and Mann-Whitney U-test.
      RESULTS: The Class II malocclusion patients had a greater final PAR index than
      Class I malocclusion patients, and similar duration (Class I - 28.95 mo. and
      Class II - 28.10 mo.) and treatment efficiency. CONCLUSION: The treatment of the
      complete Class II malocclusion with four premolar extractions presented worse
      occlusal results than Class I malocclusion owing to incomplete molar relationship
      correction.

PMID- 24918661
TI  - Postretention stability after orthodontic closure of maxillary interincisor
      diastemas.
AB  - Anterior spaces may interfere with smile attractiveness and compromise
      dentofacial harmony. They are among the most frequent reasons why patients seek
      orthodontic treatment. However, midline diastema is commonly cited as a
      malocclusion with high relapse incidence by orthodontists. OBJECTIVES: This study
      aimed to evaluate the stability of maxillary interincisor diastemas closure and
      the association of their relapse and interincisor width, overjet, overbite and
      root parallelism. MATERIAL AND METHODS: Sample comprised 30 patients with at
      least a pretreatment midline diastema of 0.5 mm or greater after eruption of the
      maxillary permanent canines. Dental casts and panoramic radiographs were taken at
      pretreatment, posttreatment and postretention. RESULTS: Before treatment, midline
      diastema width was 1.52 mm (SD=0.88) and right and left lateral diastema widths
      were 0.55 mm (SD=0.56) and 0.57 mm (SD=0.53), respectively. According to repeated
      measures analysis of variance, only midline diastema demonstrated significant
      relapse. In the overall sample the average relapse of midline diastema was 0.49
      mm (SD=0.66), whilst the unstable patients showed a mean space reopening of 0.78
      mm (SD=0.66). Diastema closure in the area between central and lateral incisors
      showed great stability. Multivariate correlation tests showed that only initial
      diastema width (beta=0.60) and relapse of overjet (beta=0.39) presented
      association with relapse of midline diastema. CONCLUSIONS: Midline diastema
      relapse was statistically significant and occurred in 60% of the sample, while
      lateral diastemas closure remained stable after treatment. Only initial diastema
      width and overjet relapse showed association with relapse of midline diastema.
      There was no association between relapse of interincisor diastema and root
      parallelism.

PMID- 24918662
TI  - Shaping ability of reciproc and TF adaptive systems in severely curved canals of
      rapid microCT-based prototyping molar replicas.
AB  - OBJECTIVE: To evaluate the shaping ability of Reciproc and Twisted-File Adaptive
      systems in rapid prototyping replicas. MATERIAL AND METHODS: Two mandibular
      molars showing S-shaped and 62-degree curvatures in the mesial root were scanned
      by using a microcomputed tomography (MUCT) system. The data were exported in the
      stereolitograhic format and 20 samples of each molar were printed at 16 um
      resolution. The mesial canals of 10 replicas of each specimen were prepared with
      each system. Transportation was measured by overlapping radiographs taken before
      and after preparation and resin thickness after instrumentation was measured by
      MUCT. RESULTS: Both systems maintained the original shape of the apical third in
      both anatomies (P>0.05). Overall, considering the resin thickness in the 62
      degree replicas, no statistical difference was found between the systems
      (P>0.05). In the S-shaped curvature replica, Reciproc significantly decreased the
      thickness of the resin walls in comparison with TF Adaptive. CONCLUSIONS: The
      evaluated systems were able to maintain the original shape at the apical third of
      severely curved mesial canals of molar replicas.

PMID- 24918664
TI  - Regulatory B cells present in lymph nodes draining a murine tumor.
AB  - In cancer, B cells have been classically associated with antibody secretion,
      antigen presentation and T cell activation. However, a possible role for B
      lymphocytes in impairing antitumor response and collaborating with tumor growth
      has been brought into focus. Recent reports have described the capacity of B
      cells to negatively affect immune responses in autoimmune diseases. The highly
      immunogenic mouse tumor MCC loses its immunogenicity and induces systemic immune
      suppression and tolerance as it grows. We have previously demonstrated that MCC
      growth induces a distinct and progressive increase in B cell number and
      proportion in the tumor draining lymph nodes (TDLN), as well as a less prominent
      increase in T regulatory cells. The aim of this research was to study B cell
      characteristics and function in the lymph node draining MCC tumor and to analyze
      whether these cells may be playing a role in suppressing antitumor response and
      favoring tumor progression. Results indicate that B cells from TDLN expressed
      increased CD86 and MHCII co-stimulatory molecules indicating activated phenotype,
      as well as intracellular IL-10, FASL and Granzyme B, molecules with regulatory
      immunosuppressive properties. Additionally, B cells showed high inhibitory upon T
      cell proliferation ex vivo, and a mild capacity to secrete antibodies. Our
      conclusion is that even when evidence of B cell-mediated activity of the immune
      response is present, B cells from TDLN exhibit regulatory phenotype and
      inhibitory activity, probably contributing to the state of immunological
      tolerance characteristic of the advanced tumor condition. 

PMID- 24918663
TI  - Erosive cola-based drinks affect the bonding to enamel surface: an in vitro
      study.
AB  - OBJECTIVE: This study aimed to assess the impact of in vitro erosion provoked by
      different cola-based drinks (Coke types), associated or not with toothbrushing,
      to bonding to enamel. MATERIAL AND METHODS: Fifty-six [Corrected] bovine enamel
      specimens were prepared and randomly assigned into seven groups (N=8): C- Control
      (neither eroded nor abraded), ERO-RC: 3x/1-minute immersion in Regular Coke (RC),
      ERO-LC: 3x/1-minute immersion in Light Coke (LC), ERO-ZC: 3x/1-minute immersion
      in Zero Coke (ZC) and three other eroded groups, subsequently abraded for 1
      minute toothbrushing (EROAB-RC, EROAB-LC and EROAB-ZC, respectively). After
      challenges, they were stored overnight in artificial saliva for a total of 24
      hours and restored with Adper Single Bond 2/Filtek Z350. Buildup coronal surfaces
      were cut in 1 mm2 -specimens and subjected to a microtensile test. Data were
      statistically analyzed by two-way ANOVA/Bonferroni tests (alpha=0.05). Failure
      modes were assessed by optical microscopy (X40). The Interface of the
      restorations were observed using Confocal Laser Scanning Microscopy (CLSM).
      RESULTS: All tested cola-based drinks significantly reduced the bond strength,
      which was also observed in the analyses of interfaces. Toothbrushing did not have
      any impact on the bond strength. CLSM showed that except for Zero Coke, all
      eroded specimens resulted in irregular hybrid layer formation. CONCLUSIONS: All
      cola-based drinks reduced the bond strength. Different patterns of hybrid layers
      were obtained revealing their impact, except for ZC.

PMID- 24918665
TI  - [Influenza: a four-year evolution of the pandemic. Prof. Alejandro Posadas
      National Hospital, Argentina].
AB  - As from January to August 2013, epidemiological weeks 1-35 (EW), Influenza
      incidence, case characteristics, types and subtypes of circulating influenza
      virus in the Nacional Profesor Alejandro Posadas Hospital were studied, and were
      compared to incidences during 2009-2012. From late May to the end of August 2013
      (EW18-35), an increase was observed in the proportion of patients' visits for
      respiratory disease, influenza-like illness and hospitalizations due to
      pneumonia; of 207 cases diagnosed with influenza A virus, 153 were infected by
      H1N1pdm09, 46 by H3, and eight without subtype. The highest proportion of cases
      was found in children under five years of age, followed by the group 60-64. The
      chances of having the illness were three times greater among the group 40-64
      years old compared to 15-39 or those older than 64. Mortality, which increased
      with age, was 7.2%, and the odds of death were six times higher among those older
      than 64. Vaccination rate among the cases was 11.6%. None of the fatal cases had
      received the vaccine. After the 2009 pandemic, the proportions of annual
      patients' visits decreased until 2012; in 2013, an increase of 52.0% during the
      winter period compared to 2012. The viral circulation started earlier in 2013
      compared to previous years. FLU-A(H1N1pdm) was the predominant circulating virus
      in 2009 and 2013, FLU-A(H3) in 2011, FLU-A(H3) and FLU-B in both 2010 and 2012. 

PMID- 24918666
TI  - [Hereditary angioedema. Treatment of acute attacks in Argentina].
AB  - In the world, hereditary angioedema (HAE) affects 1 every 50000 persons. It is
      characterized by highly disabling and recurrent episodes of cutaneous, abdominal
      and laryngeal episodes of angioedema. Asphyxia related mortality ranges from 15
      to 50%. In Argentina a plasma derived C1 inhibitor concentrate (pdC1INH) has been
      available for the treatment of acute attacks for many decades, however, only15
      (26%) out of 58 patients had received pdC1INH at least once until 2008, and only2
      (3.4%) had used it regularly. After worldwide approval of the new drugs for the
      treatment of acute HAE attacks, adding icatibant to pdC1INH in Argentina, and
      after publication of the therapeutic guide for the country, 42 (82%) out of 51
      patients from the original group has pdC1INH available to treat their next
      attack. However, 16 (18%) patients continue without access to medication and
      other 15 (35.7%) obtain their therapy spuriously through some other affected
      relative in their environment. Only 12 (28.6%) patients of the group self-treated
      at home. Access to treatment has greatly improved, but needs to be extended to
      all patients and self-treatment at home should be encouraged. 

PMID- 24918667
TI  - [Single port laparoscopic colostomy using the glove technique].
AB  - The single port surgery with glove technique is a novel process, suitable to the
      present day economic and technological moment. Colostomies are surgical
      interventions suitable to its application. We describe the surgical method and
      outcome of patients who underwent colostomy by single port glove technique within
      the years 2011 and 2012, in two hospitals in Asturias, Spain. We carried out six
      sigmoid colostomies. Four patients had tumoral pathology, another a perineal
      necrotizing fasciitis, and the sixth, a patient with Crohn's disease and complex
      perianal fistulas. The average age of the patients, four men and two women, was
      54 years (range 42-67 years). The average intervention time was 42 minutes (range
      30-65 minutes). There were no complications during the surgery or in the
      postoperative period. In our facilities material expenditure was reduced to half
      as regards other conventional single port devices. The glove technique represents
      the most economic and least invasive approach for the surgical procedure of
      stomas, in our experience considered a simple, safe and easily reproducible
      technique. 

PMID- 24918668
TI  - Association of diffuse idiopathic skeletal hyperostosis and aortic valve
      sclerosis.
AB  - The principal objective of this investigation was to analyze the association
      between diffuse idiopathic skeletal hyperostosis (DISH) and the presence of
      aortic valve sclerosis (AVS). For this study we used results from 1000
      consecutive outpatients (473 males), older than 50 years of age (average 67.6
      years), that had been examined with Doppler echocardiogram and anterior and
      lateral chest radiographs. Overall, 195 patients (19.5%) were diagnosed with DISH
      and 283 (28.3%) with AVS. DISH was more prevalent than AVS in males (66.7% vs.
      42.6%, p< 0.0001) and in older patients (73.6 +/- 9 years vs. 66.1 +/- 9 years, p
      < 0.0001). Furthermore, 55.4% of patients with dorsal DISH presented aortic
      sclerosis calcification vs. 21.7% of patients free of DISH (OR = 4.47; 95% CI =
      3.22-6.21). The adjusted odds ratio (OR) was calculated by sex and age resulting
      in 3.04 (95% CI = 2.12-4.36; p < .0001). A statistically significant association
      was found between DISH and AVS in accordance to age and sex. The biological
      plausibility of this association is based on similar risk factors, pathogenic
      mechanisms and vascular complications. 

PMID- 24918669
TI  - [Methicillin-resistant Staphylococcus aureus (MRSA) isolation in breast abscesses
      in a Public Maternity].
AB  - Mastitis and breast abscess in lactating women are risk factors for early
      breastfeeding cessation. This pathology is included in the group of skin and soft
      tissue infections. A descriptive study was performed with an advanced outlook. As
      of January 2007 through December 2011 a total of 137 breast abscesses were
      treated in our institution. We analyzed incidence, parity, postpartum days, risk
      factors, microbiological isolation and the adequacy of initial antibiotic
      treatment. In that period we observed a steady and significant increase in breast
      abscesses. Incidence from 0.19 to 0.84% in lactating women 2007 vs. 2011 p =
      0.0001 IC 95% (-0.009; 0.003), 70.6% of them primiparous and a mean interval from
      delivery to breast abscess of 41.9 +/- 35.8 days. The most frequent risk factors
      were sore nipples and breast engorgement. Staphylococcus aureus was isolated in
      82.3 to 95.0%. Methicillin resistance was higher than 60%. These strains were
      susceptible to erythromycin, clindamycin, gentamicin, rifampicin, ciprofloxacin
      and trimethoprim-sulfamethoxazol. All the cases were surgically drained; the
      initial empirical treatment was inadequate in 60% of them, 90% of patients could
      maintain breast feeding after the procedure. IN CONCLUSION: these data emphasize
      the need to prevent risk factors associated to breast abscesses: sore nipples and
      breast engorgement. In order to determine the adequate antibiotic treatment,
      bacteriological studies are required at every collection because SAMR prevalence
      varies according to diverse populations and geographic location.

PMID- 24918670
TI  - [1944 - Houssay and the creation of IBYME, Institute of Experimental Biology and
      Medicine].

PMID- 24918671
TI  - [Stress (Takotsubo) cardiomyopathy in a patient with anorexia nervosa].
AB  - We report the case of a woman with anorexia nervosa who developed takotsubo
      cardiomyopathy triggered by emotional stress and electrolyte disturbances. The
      patient improved with conservative management. Descriptions of stress
      cardiomyopathy in association with eating disorders are often of higher severity
      and related to QT prolongation because of electrolyte abnormalities, ventricular
      arrhythmias and hypoglycemia. A review of cardiovascular compromise in patients
      with anorexia nervosa is performed.

PMID- 24918672
TI  - [Intrathoracic schwannoma].
AB  - The schwannoma (neurilemmoma) is a slow-growing benign tumor originating from
      Schwann sheath whose location in the chest cavity is exceptional. It is generally
      asymptomatic and is discovered incidentally but can cause symptoms when the
      lesion grows or invade underlying structures. Its importance lies in the
      possibility of confusion with malignant tumors. We present a patient who
      complains of chest pain caused by a prolonged course schwannoma. The tomographic
      image is suggestive of extrapulmonary tumor, so the schwannoma in this location
      should be considered in the differential diagnosis of metastatic or primary
      pleural tumors such as lipoma, solitary fibrous tumor and mesothelioma. 

PMID- 24918673
TI  - [Bilateral pneumothorax complicating cavitary pulmonary metastases in
      angiosarcoma].
AB  - Metastatic pulmonary angiosarcomas are a common complication of a rare condition.
      Generally, they are presented as peripheral solid nodules, infiltrates, and
      pleural effusions. We report the case of a 65 year-old man with bilateral
      recurrent pneumothorax secondary to metastatic cavitary lesions from angiosarcoma
      of the scalp. In this case, videothoracoscopy allowed tumor resection,
      inspection, and pleurodesis. There weren't complications or tumor recurrence at
      six months follow up.

PMID- 24918674
TI  - [Spontaneous rupture of renal pelvis with retroperitoneal hematoma].

PMID- 24918675
TI  - [Mondor disease].

PMID- 24918676
TI  - [Uterine subrogation: medical and legal aspects of the first legally supported
      case in Argentina].
AB  - A woman aged 38 was referred to this center for surrogacy treatment, after
      subtotal ablation of her uterus due to a severe postpartum hemorrhage. Her
      hormonal profiles and ovarian structure were normal. The husband proved fertile
      and semen analysis was normal. The carrier, a woman 39 years old, fertile with
      two children of her own, and a long bonding friendship with the patient. After
      hormonal stimulation with gonadotropins and GnRH antagonist, six mature oocytes
      were obtained. These originated four embryos after in vitro fertilization, three
      of which were transferred to the carrier, achieving a singleton pregnancy which
      led to the birth of a normal child, now more than a year old. A lawsuit was filed
      after birth requesting the baby be registered with the biological parents name.
      The judge granted the request based on evidence and testimonies provided,
      international jurisprudence history and specification in Article 19 of the
      Argentine Constitution: "No inhabitant of the Nation shall be obliged to do what
      the law does not demand .nor be deprived of what it does not prohibit". This is
      an almost ideal example of the proceedings in a case of subrogation. However, we
      must always bear in mind the fact that in our country there is as yet no
      regulatory framework for these treatments, therefore there is a high probability
      of conflict. 

PMID- 24918677
TI  - [Ticagrelor in acute coronary syndrome. Explaining the inexplicable].
AB  - The PLATO study evaluated the efficacy of adding ticagrelor, instead of
      clopidogrel, to aspirin in patients with acute coronary syndrome, which showed
      surprisingly positive results making the drug acceptable to regulatory agencies
      and specialty societies worldwide. Notwithstanding the aforementioned success,
      contradictory information supplied by critical analysis was submitted by the
      sponsor. The controversial findings revealed several aspects that are difficult
      to explain, threatening the veracity of the study's conclusions. Mortality rate
      pattern, excessive benefit not comparable to prior studies, unexplained loss of
      follow-up development and inconsistency in findings in accordance with the
      country, the type of events arbitrator and monitoring committee are some of the
      most questionable issues. Dubious reaction to this trial is based on the fact
      that the information could not be found in published articles. This complex
      situation poses a challenge to the critical analysis of the text and raises
      questions as to how far the conflicts of financial interest influenced the
      development of the study, the communication of its results and probably,
      acceptance of the drug for commercial use. 

PMID- 24918678
TI  - [Influenza and pneumococcal immunization in cardiovascular prevention].
AB  - A group of interdisciplinary experts (cardiologists, clinicians, infectologists
      met with the purpose of analyzing the evidence revealed by the relationship
      between respiratory diseases caused by influenza, pneumococcal diseases and
      cardiovascular events, and the role played by immunization strategies applied in
      cardiovascular prevention. The present statement summarizes the conclusions
      reached by the expertise of the aforementioned professionals. Systematic
      revisions imply consistent evidence that influenza and pneumococcal infection
      lead to acute myocardial infarction and cardiovascular death. Studies published
      during the last 15 years suggest that vaccination against influenza and S.
      pneumoniae reduce the risk of acute coronary syndromes. With the current
      evidence, and considering cost-effectiveness, reducing operating expenses and
      safety profile of the vaccines, scientific societies, national and international
      government health agencies strongly recommend incorporating immunization programs
      in those patients with chronic cardiovascular disease. 

PMID- 24918679
TI  - [Mitochondria and oxidative stress participation in renal inflammatory process].
AB  - The apoptosis and renal fibrosis are processes inherent to the chronic kidney
      disease, and consequently a clear deregulation of the mitochondrial respiratory
      mechanism has been described in patients with chronic renal disease associated to
      an increase of the oxidative stress. The injured tubular cells linked to the
      interstitial macrophages and myofibroblasts produce cytokines and growth factors
      that encourage an inflammatory condition, inducing the apoptosis of the tubular
      cells and enabling the accumulation of the extracellular matrix. The angiotensin
      II has a central role in the renal fibrogenesis leading to a rapid progression of
      the chronic kidney disease. The growing levels of the angiotensin II induce pro
      inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines,
      growth factors, and oxidative stress. The current evidence suggests that the
      angiotensin II increases the mitochondrial oxidative stress, regulates the
      induction of the apoptosis and conditions the inflammatory process. Therefore the
      mitochondria and the oxidative stress would play a determinant role in the renal
      inflammatory process. Finally, this review summarizes our present knowledge
      regarding the possible mechanisms that would contribute to the apoptosis
      conditioned by inflammation and/or oxidative stress during the chronic renal
      disease. Additionally, a new concept of the anti-inflammatory tools is proposed
      to regulate the mitochondrial oxidative stress that would directly affect the
      inflammatory process and apoptosis. This concept could have positive consequences
      on the treatment of renal inflammatory pathologies and related diseases. 

PMID- 24918680
TI  - [Perfectioning medicine].

PMID- 24918681
TI  - [Granulomatosis with polyangiitis].

PMID- 24918682
TI  - [More about the name Wegener granulomatosis].

PMID- 24918683
TI  - [Gnathostomiasis after travelling].

PMID- 24918684
TI  - [About a probable case of gnathostomiasis].

PMID- 24918685
TI  - [Is there gnathostomiasis in Colombia? Reflections from a possible case imported
      to Argentina].

PMID- 24918686
TI  - [In response: on a possible case of gnathostomiasis].

PMID- 24918687
TI  - [The natriuretic peptide system and its biomarkers].

PMID- 24918688
TI  - [Natriuretic peptides in non-cardiac diseases].

PMID- 24918689
TI  - Assessment of disease progression and functional benefit in neurodegenerative
      disease: can we tell the difference?
AB  - Therapeutic strategies for neurodegenerative diseases include modalities intended
      to modulate disease progression as well as those whose intent is to improve or
      maintain functional capacity. As the search for pharmacodynamic markers has
      proved elusive, treatment outcomes most commonly reflect patient function. As a
      result, even when clinical trials show a beneficial effect, the underlying
      etiology of that benefit can be difficult to determine. This review summarizes
      recent trials in ALS and Parkinson's disease, with the goal of increasing
      understanding of how the choice of outcome measures influences what can be
      concluded from the results. Although most ALS trials have been negative in recent
      years, outcomes are reviewed in terms of potential conclusions that could have
      been drawn. Functional benefit has been established in a number of recent trials;
      however, the outcomes used have lead to uncertainty as to whether specific agents
      modify disease or alter function. In the absence of specific markers sensitive to
      alteration of disease specific pathways, the distinction between agents that
      alter underlying disease versus those that affect function may depend on
      underlying hypotheses rather than clinical trial results.

PMID- 24918690
TI  - Gastric coronary vein to portal vein reconstruction in liver transplant: case
      report.
AB  - OBJECTIVES: Portal vein thrombosis is a common complication in end-stage liver
      diseases of candidates for liver transplant. Most portal vein thromboses can be
      removed with thrombectomy. However, if the thrombosis extends to the distal
      superior mesenteric vein, it is difficult to reconstruct the portal vein. We
      report herein a case of dilated gastric coronary vein to portal vein
      reconstruction in liver transplant. CASE REPORT: During the operation, the portal
      vein thrombosis was confirmed; it extended to the distal superior mesenteric
      vein. It could not be removed, and a jumping graft vein could not be used either.
      The dilated gastric coronary vein was dissected. After a piggy-back caval
      anastomosis, the recipient gastric coronary vein was anastomosed to donor portal
      vein using side-to-end anastomosis. Successive ultrasound studies demonstrated
      patent portal anastomosis. At postoperative day 30, computed tomography scans
      confirmed the patency of the portal anastomosis. The patient recovered fully and
      at the time of this writing, was doing well 1 year after transplant. Neither
      ascites nor upper gastrointestinal bleeding occurred. CONCLUSIONS: If complete
      portal vein thrombosis extends to the distal superior mesenteric vein, and a
      jumping graft vein cannot be applied, the recipient gastric coronary vein or
      other collateral varix anastomosed to the donor portal vein is an alternative.

PMID- 24918692
TI  - Controlling the sign and magnitude of screw-sense preference from the C-terminus
      of an achiral helical foldamer.
AB  - The global screw-sense preference of an achiral helical oligomer may be
      controlled by a single chiral monomer located at one terminus. Remarkably,
      maximal control is induced in oligomers of the achiral quaternary amino acid Aib
      by a single C-terminal alaninamide residue, probably because the Ala side chain,
      though small, is compatible with a 310 helical conformation. The presence or
      absence of a C-terminal hydrogen bond donor determines the screw sense of the
      entire oligomer. 

PMID- 24918691
TI  - Essential oil alloaromadendrene from mixed-type Cinnamomum osmophloeum leaves
      prolongs the lifespan in Caenorhabditis elegans.
AB  - Cinnamomum osmophloeum Kaneh. is an indigenous tree species in Taiwan. The
      present study investigates phytochemical characteristics, antioxidant activities,
      and longevity of the essential oils from the leaves of the mixed-type C.
      osmophloeum tree. We demonstrate that the essential oils from leaves of mixed
      type C. osmophloeum exerted in vivo antioxidant activities on Caenorhabditis
      elegans. In addition, minor (alloaromadendrene, 5.0%) but not major chemical
      components from the leaves of mixed-type C. osmophloeum have a key role against
      juglone-induced oxidative stress in C. elegans. Additionally, alloaromadendrene
      not only acts protective against oxidative stress but also prolongs the lifespan
      of C. elegans. Moreover, mechanistic studies show that DAF-16 is required for
      alloaromadendrene-mediated oxidative stress resistance and longevity in C.
      elegans. The results in the present study indicate that the leaves of mixed-type
      C. osmophloeum and essential oil alloaromadendrene have the potential for use as
      a source for antioxidants or treatments to delay aging. 

PMID- 24918693
TI  - Evaluation of the effects of recipient/donor gender on early/late postoperative
      renal graft functions by renal scintigraphy.
AB  - OBJECTIVES: We discuss the effects of recipient/donor gender on renal allograft
      functions using scintigraphic parameters obtained 3 days after renal transplant
      and 1 year after transplant. MATERIALS AND METHODS: This retrospective study
      included 76 renal allograft recipients (group one, 38 males; group two, 38
      females). Patients underwent scintigraphic imaging with Tc-99m DTPA on
      postoperative day 3 and 1 year after transplant. We used the Hilson perfusion
      index, maximum renal activity/background activity, ratio of renal activity at 20
      minutes to renal activity at 3 minutes, time-to-peak activity, and glomerular
      filtration rate to measure quantitative parameters. RESULTS: On postoperative day
      3, the Hilson perfusion index, maximum renal activity/background activity, the
      ratio of renal activity at 20 minutes to renal activity at 3 minutes, time-to
      peak activity, and glomerular filtration rate values for male/female recipients
      were similar (P = .65, P = .77, P = .38, P = .10, P = .99). The gender of donors
      was compared with the above-mentioned scintigraphic parameters of the recipients,
      and no statistically significant differences were found (P = .24, P = .25, P =
      .44, P = .29, P = .13). At 1-year follow-up, values obtained from group 1 and
      group 2 recipients were similar. After 1 year, chronic rejection developed in
      15.7% of group 1 recipients and in 10.5% of group 2 recipients; acute rejection
      developed in 21% of group 1 recipients and in 23.6% of group 2 recipients. There
      were no statistically significant differences between the occurrence of acute
      rejection and the gender of recipients or donors (P = 1.00, P = .45).
      CONCLUSIONS: We observed no statistically significant differences between renal
      graft functions and gender of the recipients/donors during the early/late
      posttransplant period.

PMID- 24918695
TI  - Oriental cholangiohepatitis - is our surgery appropriate?
AB  - Oriental cholangiohepatitis, or recurrent pyogenic cholangitis is only noted in
      certain parts of the world, especially South East Asia. Due to increasing
      immigration the disease is now being seen in western countries also. Treating
      physicians may face difficulty in managing such cases due to lack of exposure.
      Furthermore management of such cases is not standardized because of lack of a
      universally accepted classification system. Here we review the disease and share
      our long experience with management of these patients. 

PMID- 24918694
TI  - Expression of human solute carrier family transporters in skin: possible
      contributor to drug-induced skin disorders.
AB  - Solute carrier (SLC) transporters play important roles in absorption and
      disposition of drugs in cells; however, the expression pattern of human SLC
      transporters in the skin has not been determined. In the present study, the
      expression patterns of 28 human SLC transporters were determined in the human
      skin. Most of the SLC transporter family members were either highly or moderately
      expressed in the liver, while their expression was limited in the skin and small
      intestine. Treatment of human keratinocytes with a reactive metabolite of
      ibuprofen significantly reduced cell viability. Expression array analysis
      revealed that S100 calcium binding protein A7A (S100A7A) was induced nearly 50
      fold in dermal cells treated with ibuprofen acyl-glucuronide. Determination of
      the expression of drug-metabolizing enzymes as well as drug transporters prior to
      the administration of drugs would make it possible to avoid the development of
      idiosyncratic skin diseases in individuals. 

PMID- 24918696
TI  - Total thyroidectomy with harmonic scalpel combined to gelatin-thrombin matrix
      hemostatic agent: is it safe and effective? A single-center prospective study.
AB  - INTRODUCTION: Hemostasis during thyroidectomy is essential; however, the safest,
      most efficient and cost-effective way to achieve this is unclear. The aim of this
      study was to evaluate the outcome of total thyroidectomy (TT) performed with
      combination of harmonic scalpel (HS) and Floseal. METHODS: Patients undergone TT
      were divided into two groups: HS + Floseal and traditional hemostasis groups. The
      primary endpoint was 24-h drain output and blood-loss requiring reintervention.
      Secondary endpoints included surgery duration, postsurgical complications and
      hypocalcemia rates. RESULTS: Between September 2012 and January 2014, 165
      patients were enrolled (100 to HS + Floseal, 65 to standard hemostasis); 80.5%
      female; mean age 42.3 years. The 24-h drain output was lower in the HS + Floseal
      group compared with standard TT. HS + Floseal also had a shorter mean surgery
      time (p < 0.0001) vs standard TT. No differences in post-surgical complications
      and in hypocalcemiarates between groups. CONCLUSION: combination of Floseal plus
      the HS is effective and safe for TT and it provides a complementary hemostatic
      approach.

PMID- 24918697
TI  - Vitamin D level and risk of community-acquired pneumonia and sepsis.
AB  - Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels
      is associated with acute infectious illness. The relationship between vitamin D
      status, measured prior to acute infectious illness, with risk of community
      acquired pneumonia (CAP) and sepsis has not been examined. Community-living
      individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season
      matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph
      confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to
      hospitalization. Regression models adjusted for diabetes, renal disease, and
      peripheral vascular disease evaluated the association of 25(OH)D levels with CAP
      or sepsis risk. A total of 132 CAP patients and controls were 60 +/- 17 years,
      71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio
      (OR) 2.57, 95% CI 1.08-6.08) were strongly associated with increased odds of CAP
      hospitalization. A total of 422 sepsis patients and controls were 65 +/- 14
      years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR
      1.75, 95% CI 1.11-2.77) were associated with increased odds of sepsis
      hospitalization. Vitamin D status was inversely associated with risk of CAP and
      sepsis hospitalization in a community-living adult population. Further clinical
      trials are needed to evaluate whether vitamin D supplementation can reduce risk
      of infections, including CAP and sepsis. 

PMID- 24918698
TI  - Effect of vitamin D supplementation on the level of circulating high-sensitivity
      C-reactive protein: a meta-analysis of randomized controlled trials.
AB  - Vitamin D might elicit protective effects against cardiovascular disease by
      decreasing the level of circulating high-sensitivity C-reactive protein (hs-CRP),
      an inflammatory marker. Thus, we conducted a meta-analysis of randomized
      controlled trials to evaluate the association of vitamin D supplementation with
      circulating hs-CRP level. A systematic literature search was conducted in
      September 2013 (updated in February 2014) via PubMed, Web of Science, and
      Cochrane library to identify eligible studies. Either a fixed-effects or a random
      effects model was used to calculate pooled effects. The results of the meta
      analysis of 10 trials involving a total of 924 participants showed that vitamin D
      supplementation significantly decreased the circulating hs-CRP level by 1.08 mg/L
      (95% CI, -2.13, -0.03), with the evidence of heterogeneity. Subgroup analysis
      suggested a higher reduction of 2.21 mg/L (95% CI, -3.50, -0.92) among
      participants with baseline hs-CRP level >=5 mg/L. Meta-regression analysis
      further revealed that baseline hs-CRP level, supplemental dose of vitamin D and
      intervention duration together may be attributed to the heterogeneity across
      studies. In summary, vitamin D supplementation is beneficial for the reduction of
      circulating hs-CRP. However, the result should be interpreted with caution
      because of the evidence of heterogeneity. 

PMID- 24918699
TI  - Effect of the combination of metformin hydrochloride and melatonin on oxidative
      stress before and during pregnancy, and biochemical and histopathological
      analysis of the livers of rats after treatment for polycystic ovary syndrome.
AB  - The aim of the present study was to analyze the effect of a combination of
      metformin hydrochloride and melatonin on oxidative stress together with a
      biochemical and histopathological analysis of the livers of Wistar rats induced
      with PCOS. The results indicated that a combination of the drugs was more
      effective in the reduction of plasmatic levels of liver enzyme alanine
      aminotransferase, nitric oxide and total glutathione, and decreased the
      inflammatory response and histopathological damage, producing results that were
      significantly similar to animals from the control group. A mixture of the drugs
      produced more effective results against liver toxicity caused by PCOS,
      encouraging the normalization of biochemical parameters. During pregnancy, there
      was reduced oxidative stress compared to monotherapeutic use of these drugs.
      Interestingly, the combination of the drugs caused a physiological reaction
      similar to responses identified in healthy rats without induction of the PCOS
      control group. However, the clinical and physiological effectiveness of the
      combination should be further explored, especially with respect to the possible
      side effects on offspring. 

PMID- 24918701
TI  - Nasal reconstruction--the challenge "par excellence" for plastic surgery.

PMID- 24918700
TI  - Evaluation of polyethylene glycol-conjugated novel polymeric anti-tumor drug for
      cancer therapy.
AB  - A novel polymeric prodrug (PXPEG) was prepared to enhance the solubility of an
      anti-cancer drug, paclitaxel, in aqueous solutions and decrease the cytotoxicity
      by PEGylation, which means PEG attached to another molecule. In addition, the
      targeting ligand, transferrin (TF), was modified to PXPEG to enhance the
      therapeutic efficacy. The targeting ligand-modified PXPEG (TFPXPEG) was examined
      by (1)H-NMR to confirm the successful synthesis. The synthesized TFPXPEG had
      better solubility than the free drug against aqueous solution. The particle size
      of TFPXPEG was approximately 197.2nm and it had a spherical shape. The MTT assay
      showed that the anti-tumor efficiency of TFPXPEG was better than that of TF
      unmodified PXPEG. In the KB tumor-bearing mouse model, the tumor volume of
      TFPXPEG treated groups was decreased dramatically by more than 2 fold or 3 fold
      compared to the PBS or PXPEG treated groups. The in vitro and in vivo evaluation
      showed that TFPXPEG had better efficacy than that of PXPEG due to the targeting
      effect of targeting ligands, such as TF. 

PMID- 24918702
TI  - History of reconstructive rhinoplasty.
AB  - Amputation of the nose was practiced as a sign of humiliation to adulterers,
      thieves, and prisoners of war by certain ancient populations. To erase this
      disfigurement, numerous techniques were invented over the centuries. In India,
      where this injury was common, advancement cheek flaps were performed (around 600
      BC). The forehead flap was introduced much later, probably around the 16th
      century. The Venetian adventurer Manuzzi, in writing a report about the Mughal
      Empire in the second half of the 17th century gave the description of the
      forehead rhinoplasty. Detailed information concerning the Indian forehead flap
      reached the Western world in 1794, thanks to a letter to the editor that appeared
      in the Gentleman's Magazine. From this episode, one can date the beginning of a
      widespread interest in rhinoplasty and in plastic surgery in general. In Europe,
      nasal reconstruction started in the 15th century in Sicily with the Brancas,
      initially with cheek flaps and then with arm flaps. At the beginning of the 16th
      century, rhinoplasty developed in Calabria (Southern Italy) with the Vianeos. In
      1597, Gaspare Tagliacozzi, Professor of Surgery at Bologna, improved the arm flap
      technique and published a book entirely devoted to this art. He is considered the
      founder of plastic surgery. 

PMID- 24918703
TI  - Histological control of tumor surgical margins with three-dimensional histology.
AB  - Three-dimensional (3D) histology provides a complete 3D representation of the
      margins of a tumor specimen on histological slides. This eliminates diagnostic
      gaps and provides maximum sensitivity in identifying tumor outgrowths. The method
      is used to confirm tumor-free margins or, in case of an incomplete tumor
      resection, to make even very small infiltrated areas visible with topographic
      orientation. The basic principle of 3D histology is the conversion from the 3D
      structure of the tumor-specimen margins into a two-dimensional view of
      histological sections. The 3D margins are flattened with their outside down and
      then cut into pieces, suitable for histopathological procedures of cryo or
      paraffin sections. The management of a full 3D histology needs a tight
      communication between the surgeon and the pathologist. Clear and safe rules are
      necessary to enable both the surgeon and the pathologist to point out areas of
      incomplete tumor excisions very precisely. Using a circle as representation of
      the separation between tumor base and margin, the pathologist can point out the
      exact position of an outgrowth by referring to different positions on the circle
      in clock times. This system will be sufficient to point out tumor outgrowths. The
      advantage is that it is very simple to communicate and easy implemented in any
      electronic communication. 

PMID- 24918704
TI  - Skin-fat-graft: a simple tool for reconstruction of small deep defects of the
      nose.
AB  - Small deep defects of the nose after resection of benign or malignant skin tumors
      are a common challenge in facial plastic surgery daily routine. The use of local
      flaps has several disadvantages for what reason they are a minor or no option
      especially in certain localizations in the lower third of the nose. Many elder
      patients suffer from comorbidities where complex more-staged reconstructional
      procedures drop out. We present a technique of nasal defect closure with a skin
      fat composite graft. Between April 2010 and July 2013, we treated 42 patients
      with a total of 46 skin-fat-grafts to the nose. We reevaluated the esthetic and
      functional outcome in a retrospective analysis. In 80% of the cases, the results
      were rated excellent to satisfactory, 20% fair to poor. Reasons for worse
      validation were color and contour differences of grafts and surrounding tissue as
      well as alar retraction in very few cases. Nevertheless, we consider skin-fat
      grafts to be a useful tool in single-layer nasal reconstruction in defects of
      smaller size. 

PMID- 24918705
TI  - One-stage nasal soft tissue reconstruction with local flaps.
AB  - Because of better public education and earlier diagnosis of skin tumors, the
      number of soft tissue defects of the nose with limited size and depth after tumor
      resection is increasing. A variety of surgical methods such as skin grafts,
      regional flaps such as forehead flap, and local flaps have been described. The
      method of choice is dependent on the defect size, localization, skin structure
      and the wishes and expectations, and general condition of the patient. Nasal
      reconstruction for soft tissue defects in the supratip area, dorsum, and
      sidewalls using local rotation and/or advancement flaps is our primary option.
      But achieving supreme results with these non-subunit-based techniques is still a
      challenge. Showing schematic figures and case studies, this article is aimed at
      assisting surgeons in the planning and decision making of which flap is
      appropriate for the reconstruction of soft tissue defects of the nose. 

PMID- 24918706
TI  - Open rhinoplasty concepts in facilitating tip reconstruction.
AB  - The nose is a frequent site for skin cancer, accounting for approximately 26% of
      basal cell carcinomas and approximately 13% of spinal cell carcinomas of the
      facial district. Also melanomas, mostly as lentigo maligna melanomas, are
      frequently located at the nasal pyramid. Although defects can be of varying size
      and depth, some even involving the whole trilaminar structure of the nose, most
      remain superficial and seldom reach and infiltrate the underlying framework. In
      contrast, they can be wide, thus requesting large flaps to resurface the defect.
      Although a technically well-planned and well-performed surgery can lead to
      excellent aesthetic results, scars from both donor and recipient sites can be
      noticeable. Since skin cancers generally affect older people, we often deal with
      aged noses. Such noses typically present some common features such as plunging
      tip, increased length, and a prominent hump due to several reasons, already well
      described in the literature. In this scenario, by reducing and addressing the
      framework, we can obtain a variable quota of downsizing of the original defect,
      thus requiring less skin for coverage, and thus reducing the size of needed flaps
      and consequent scars. This is greatly facilitated by the open rhinoplasty
      approach. Most of the maneuvers aimed at reducing the framework are indeed the
      same. 

PMID- 24918707
TI  - Reconstruction of nasal alar defects with freestyle facial artery perforator
      flaps.
AB  - In 2009, we have described the use of freestyle facial artery perforator flaps
      for one-stage nose reconstruction. Since then, several articles have reported the
      use of facial artery perforator flaps for nose reconstruction. The purpose of
      this article is to provide an update of the published technique after 10 years of
      experience. Since 2004, 21 patients have been treated with a freestyle facial
      artery perforator flap for one-stage reconstruction of the nasal ala. The flaps
      were 16 propellers, 4 V-Y, and 1 island transposition. A single venous congestion
      leading to a minor flap tip necrosis and a wound dehiscence was observed. All
      other flaps healed uneventfully. The V-Y design and multiple subunit
      reconstruction gave suboptimal results. It was concluded that indications for
      freestyle facial artery perforator flaps are total nasal alar subunit
      reconstruction or reconstruction of lateral alar defects when perforator anatomy
      allows. In these cases, freestyle facial artery perforator flaps are the first
      choice technique at our institution because they allow excellent results in one
      stage operation. One-stage nasal ala reconstruction with freestyle facial artery
      perforator flaps. 

PMID- 24918708
TI  - Lining in nasal reconstruction.
AB  - Restoring nasal lining is one of the essential parts during reconstruction of
      full-thickness defects of the nose. Without a sufficient nasal lining the whole
      reconstruction will fail. Nasal lining has to sufficiently cover the shaping
      subsurface framework. But in addition, lining must not compromise or even block
      nasal ventilation. This article demonstrates different possibilities of lining
      reconstruction. The use of composite grafts for small rim defects is described.
      The limits and technical components for application of skin grafts are discussed.
      Then the advantages and limitations of endonasal, perinasal, and hingeover flaps
      are demonstrated. Strategies to restore lining with one or two forehead flaps are
      presented. Finally, the possibilities and technical aspects to reconstruct nasal
      lining with a forearm flap are demonstrated. Technical details are explained by
      intraoperative pictures. Clinical cases are shown to illustrate the different
      approaches and should help to understand the process of decision making. It is
      concluded that although the lining cannot be seen after reconstruction of the
      cover it remains one of the key components for nasal reconstruction. When dealing
      with full-thickness nasal defects, there is no way to avoid learning how to
      restore nasal lining. 

PMID- 24918709
TI  - Update on the septal pivot flap.
AB  - The septal pivot flap has been an integral part of my concept for total and
      subtotal nasal repair. Since 2004, I have performed 15 reconstructions, in 9
      cases combined with a pivot flap. The three-stage procedure starts with
      reconstruction of the septum by lifting the flap if available and needed. In the
      nine patients, all flaps could be rotated smoothly and without necrosis,
      contributing a minor or even major portion of nasal lining in every case. The
      neoseptum provided a strong static support, thus preparing the ground for
      significantly good projection, protection, and definition of profile and tip.
      This article illustrates the basic technique step by step and presents four
      typical cases. 

PMID- 24918711
TI  - Nasal reconstruction with the paramedian forehead flap--details for success.
AB  - This article is focused on technical details for successfully reconstructing the
      nasal skin cover in parts or totally. Nasal reconstruction is based on the
      successful reconstruction of the inner lining and the nasal framework in three
      layer defects. The details to be considered include planning the flap, subunit
      reconstruction and outline of margins, dealing with hair-bearing forehead skin,
      sequence of stages, intermediate debulking, details of pedicle dissection, brow
      reconstruction, forehead closure, forehead expansion, and complication
      management. 

PMID- 24918710
TI  - Framework fabrication with rib cartilage in partial and total nasal
      reconstruction.
AB  - The framework reconstruction of the nose is a significant and complex component
      of its partial or total reconstruction. On the one hand, the design of the
      individual framework parts is based on the anatomic nature of available rib or
      ear cartilage, which must on the other hand be adapted to the anatomic
      characteristics of the defect. The framework parts must be anchored not only to
      each other but also stably to the facial skeleton. The symmetry of the framework
      reconstruction is an essential component of the aesthetics of the reconstructed
      nose. If these points are already considered in planning, the reconstruction of
      the nasal framework can be standardized insofar as the same principles for the
      basic design of the individual parts as well as stable solutions for the
      anchoring points can be chosen. With reproducible techniques, functionally and
      aesthetically good to very good results can be achieved, including in the long
      term. The surgeon must possess special skills in the field of nasal
      reconstruction to correctly choose, apply, and combine the various techniques of
      nasal framework reconstruction. 

PMID- 24918712
TI  - A propeller flap for single-stage nose reconstruction in selected patients:
      supratrochlear artery axial propeller flap.
AB  - The paramedian forehead flap is the gold standard technique for nose
      reconstruction. It requires two different surgical operations which prolonged the
      postoperative dressing and care. We present our 5-year experience with a
      propeller flap based on the supratrochlear artery, which allows one-stage
      transfer of the forehead skin to the nose without the need for pedicle division.
      This technique is indicated in a selected group of patients who are not suitable
      for multiple-stage reconstructions because they have concurrent medical
      conditions, reduced mobility, or live far away from specialized medical centers.
      We have renamed this procedure as supratrochlear artery axial propeller flap,
      from the acronym STAAP flap, to stress the axial, well known and constant,
      vascularization of the flap. In the past 5 years, we have been performing 25
      STAAP flaps; full-thickness nasal reconstruction was performed in 11 cases. The
      patients were 16 males and 9 females, with a mean age of 79.5 years. All patients
      had multiple comorbidities. Complete flap survival was observed in 23 cases and
      healing was complete in 7 days. In two cases, there was a partial distal necrosis
      of the flap treated conservatively. Cosmetic results were good and the patient's
      satisfaction was significant. These results indicate that the STAAP flap is a
      reliable and useful technique in selected cases, as old or noncompliant patients
      who benefit from a one-stage technique of nose reconstruction. 

PMID- 24918713
TI  - Revising or redoing an imperfect or failed nasal reconstruction.
AB  - Almost all major nasal reconstructions will require a late revision to refine
      aesthetics and function. The early surgical result after pedicle division will be
      determined by the materials, methods, priorities, planning, and surgical stages
      chosen by the surgeon. Imperfections in nasal contour, including recreation of
      the alar crease and nasolabial fold, are corrected by soft tissue debulking and
      secondary cartilage grafting through peripheral or direct incisions. The nostrils
      are enlarged by soft tissue excision and local tissue rearrangement.
      Occasionally, the original repair must be discarded and a second regional flap
      used to "redo" the reconstruction. Success is determined by careful analysis of
      the visual deformity, regional principles of the subunit reconstruction, and
      careful planning. 

PMID- 24918714
TI  - Nasal reconstruction in children.
AB  - The nose represents the center of the face. The nasal shape changes with the
      progression from infancy to adulthood. In newborns, the main supporting structure
      of the nose is the dorsal septal cartilage; it is the facial growth center. The
      loss of septal cartilage at different ages leads to various facial syndromes
      involving the nose, maxilla, and orbita. Therefore, every surgical treatment can
      compromise not only the nasal growth but also the growth of the whole face.
      Childhood trauma or a malformation of the nose can also cause enormous functional
      impairments similar to those caused by surgical treatments. Our contribution
      represents different aspects of nasal deformities and their treatment. An
      individual concept is indispensable to reach the best compromise in all cases.
      The postulate of an early treatment gives priority to physical and mental damage
      control. The late therapy concept uses the inimitable potential of the growth of
      different tissues needed for a septoplasty and should be protected from
      iatrogenic impairment. We recommend a first-line pediatric nasal reconstruction,
      an attentive follow-up, and finally, a secondary nasal reconstruction in the
      adult patient if required for achieving normalcy. 

PMID- 24918715
TI  - Nasal reconstruction in heminasal deficiency (proboscis lateralis): two case
      reports, with airway reconstruction in one case.
AB  - Proboscis lateralis is a very rare congenital malformation with heminasal
      hypoplasia or aplasia. The affected side is represented by a trunk (proboscis)
      which can be positioned from the upper eyelid down to the alar base. We present
      two cases of proboscis lateralis, one in which we reconstructed an airway. The
      first case is a 16-year-old male patient who presented with heminasal aplasia.
      Immediately after birth, a proboscis lateralis was resected from the right upper
      eyelid as primary treatment elsewhere. We reconstructed the nose using costal
      cartilage as framework. A paramedian forehead flap was transposed to give the
      patient a nose with adult dimensions. We made no attempt to reconstruct an airway
      in this case as unilateral nasal breathing appeared adequate. The second case is
      a 14-year-old male patient who presented with heminasal aplasia on his right
      side, where a nodule-like appendix was existent with a fistula underneath. A
      computed tomographic scan revealed an existing hypoplastic posterior nasal airway
      and a complete ventilated sinus system. The fact that there was an existing
      posterior airway encouraged us to construct an anterior airway to create an
      airflow passage. Costal cartilage was taken for framework reconstruction and
      nasal skin was completely replaced by a paramedian forehead flap. The
      reconstructed airflow passage was stable. 

PMID- 24918717
TI  - Selective fluorescence detection of monosaccharides using a material composite
      formed between graphene oxide and boronate-based receptors.
AB  - We have developed a novel class of simple materials for sensing monosaccharides
      by the functionalization of graphene oxide (GO) with boronate-based fluorescence
      probes (BA1 and BA2). The composite materials were characterized by atomic force
      microscopy, Raman spectroscopy, and UV-vis/fluorescence spectroscopy. The strong
      fluorescence of the BA probes is quenched in the presence of GO through
      fluorescence resonance energy transfer. The BA@GO composite sensors formed
      provide a useful platform for fluorogenic detection of monosaccharides based on
      the strong affinity between the boronic acid receptor and monosaccharides. The
      BA@GO composite sensor displayed a "turn-on" fluorescence response with a good
      linear relationship toward fructose over a range of other saccharides. 

PMID- 24918716
TI  - Dual protonophore-chitinase inhibitors dramatically affect O. volvulus molting.
AB  - The L3-stage-specific chitinase OvCHT1 has been implicated in the development of
      Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known
      anthelmintic drug, was previously discovered as a potent and specific OvCHT1
      inhibitor. As closantel is also a known protonophore, we performed a simple
      scaffold modulation to map out the structural features that are relevant for its
      individual or dual biochemical roles. Furthermore, we present that either OvCHT1
      inhibition or protonophoric activity was capable of affecting O. volvulus L3
      molting and that the presence of both activities in a single molecule yielded
      more potent inhibition of the nematode's developmental process. 

PMID- 24918718
TI  - [Polycystic ovary syndrome: the visible and invisible associate with
      cardiovascular risk].

PMID- 24918719
TI  - Surgical treatment of subcostal incisional hernia with polypropylene mesh -
      analysis of late results.
AB  - OBJECTIVE: To evaluate the results of subcostal incisional hernia repair using
      polypropylene mesh, the technical aspects of musculo-aponeurotic reconstruction,
      routine fixation of supra-aponeurotic mesh and follow-up for five years. METHODS:
      We conducted a retrospective study that assessed 24 patients undergoing subcostal
      incisional hernia repair with use of polypropylene mesh; 15 patients (62.5%) were
      female; ages ranged from 33 to 82, and 79.1% had comorbidities. RESULTS: Early
      complications: three cases (12.5%) of wound infection, three cases (12.5%) of
      seroma, one case (4.1%) of hematoma; and one case (4.1%) of wound dehiscence.
      Late complications occurred in one case (4.1%) of hernia recurrence attributed to
      technical failure in the fixation of the mesh and in one case (4.1%) of chronic
      pain. There were no cases of exposure or rejection of the mesh. CONCLUSION: The
      subcostal incisional hernia, though not very relevant, requires adequate surgical
      treatment. Its surgical correction involves rebuilding the muscle-aponeurotic
      defect, supra-aponeurotic fixation of polypropylene mesh, with less complexity
      and lower rates of complications and recurrences.

PMID- 24918720
TI  - Local control of human papillomavirus infection after anal condylomata acuminata
      eradication.
AB  - OBJECTIVE: To verify whether the eradication of anal condylomata acuminata was
      effective for local control of HPV infection using anal colposcopy and anal brush
      cytology. METHODS: We evaluated 147 patients treated for anal margin and/or anal
      canal condyloma, with 108 HIV-positive and 39 HIV-negative individuals. The
      average age for males was 40 years for HIV-positive and 27.5 for HIV-negative. In
      females, the mean age was 37.5 years for HIV-positive and 31.5 for HIV-negative.
      RESULTS: Twenty-four patients (16.3%) had normal cytology and anal colposcopy, 16
      (10.9%) normal cytology and altered anal colposcopy, 52 (35.4%) normal anal
      colposcopy and altered cytology, and 55 (37.4%) had altered cytology and anal
      colposcopy. CONCLUSION: the eradication of clinical lesions failed to locally
      control HPV infection.

PMID- 24918721
TI  - Postoperative topical analgesia of hemorrhoidectomy with policresulen and
      cinchocaine: a prospective and controlled study.
AB  - OBJECTIVE: To evaluate the effects of topical policresulen and cinchocaine in the
      postoperative pain behavior of open hemorrhoidectomy. METHODS: We conducted a
      prospective, double-blinded, controlled study. The control group received the
      usual guidelines with oral medications. The topical treatment group received, in
      addition, the application of the ointment and was comprised of two subgroups
      (policresulen + cinchocaine, and placebo). Pain intensity was recorded with the
      visual analogue scale. RESULTS: 43 patients were operated on: control group - n =
      13, one excluded; placebo - n = 15; and policresulen + cinchocaine - n = 15. The
      mean age was 45.98 years and 37.2% were men. The average pain intensity was 4.09
      (immediate postoperative), 3.22 (hospital discharge), 5.73 (day 1) , 5.77 (day
      2), 5.74 (day 3), 5.65 (day 7), 5.11 (day 10), 2.75 (day 15) and 7.70 (first
      bowel movement), with no difference between groups in all periods. CONCLUSION:
      This study showed no reduction in pain after hemorrhoidectomy with the use of
      topical policresulen and cinchocaine.

PMID- 24918722
TI  - Incidence of uterine post abortion infection at Hospital de Clinicas de Porto
      Alegre. Is prophylactic antibiotic necessary?
AB  - OBJECTIVE: To identify the incidence of pelvic infection after miscarriage
      undergoing uterine evacuation in a tertiary hospital in southern Brazil and to
      compare with the international literature. METHODS: we reviewed electronic
      medical records of the Hospital de Clinicas de Porto Alegre of all patients who
      underwent uterine evacuation for miscarriage between August 2008 and January 2012
      were reviewed. We included all patients submitted to uterine curettage due to
      abortion and who had outpatient visits for review after the procedure. We
      calculated emographic and laboratory data of the study population, number needed
      for treatment (NNT) and number needed to harm (NNH). RESULTS: of the 857 revised
      electronic medical records, 377 patients were subjected to uterine evacuation for
      miscarriage; 55 cases were lost to follow-up, leaving 322 cases that were
      classified as not infected abortion on admission. The majority of the population
      was white (79%); HIV prevalence and positive VDRL was 0.3% and 2%, respectively.
      By following these 322 cases for a minimum of seven days, it was found that the
      incidence of post-procedure infection was 1.8% (95% CI 0.8 to 4). The NNT and NNH
      calculated for 42 months were 63 and 39, respectively. CONCLUSION: The incidence
      of post-abortion infection between August 2008 to January 2012 was 1.8% (0.8 to
      4).

PMID- 24918723
TI  - Polycystic ovary syndrome: implications of metabolic dysfunction.
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) and its
      clinical interrelations in polycystic ovary syndrome (PCOS). METHODS: This was a
      cross-sectional, prospective study with 100 patients with diagnosed PCOS based on
      the consensus of Rotterdam (2003). We investigated the interrelationships of MS,
      with intrinsic PCOS data. Dermatological profile was analyzed, in addition to
      acanthosis nigricans (AN) in the presence of hirsutism and acne. The use of HOMA
      IR (homeostatic model assessment of insulin resistance) aimed at the correlation
      with MS in order to establish the metabolic dysfunction with the state of insulin
      resistance. RESULTS: The mean and standard deviations corresponding figures for
      age, body mass index and waist circumference were, respectively, 25.72 (+/-
      4.87), 30.63 (+/- 9.31) and 92.09 (+/- 18.73). The prevalence of MS was 36% and
      significantly correlated with BMI, AN, and in 51% of patients the state of
      insulin resistance (HOMA-IR). Regarding skin profile, only AN significant
      correlation with MS. CONCLUSION: We propose the routine inspection of metabolic
      components related to severe PCOS. These parameters configure the cardiovascular
      risk and such conduct is of undoubted importance to public health.

PMID- 24918724
TI  - Influence of distal ileum exclusion on hepatic and renal functions in presence of
      extrahepatic cholestasis.
AB  - OBJECTIVE: To verify whether the ileal exclusion interferes with liver and kidney
      functional changes secondary to extrahepatic cholestasis. METHODS: We studied 24
      rats, divided into three groups with eight individuals each: Group 1 (control),
      Group 2 (ligation of the hepatic duct combined with internal biliary drainage),
      and Group 3 (bile duct ligation combined with internal biliary drainage and
      exclusion of the terminal ileum). Animals in Group 1 (control) underwent sham
      laparotomy. The animals of groups 2 and 3 underwent ligation and section of the
      hepatic duct and were kept in cholestasis for four weeks. Next, they underwent an
      internal biliary bypass. In Group 3, besides the biliary-enteric bypass, we
      associated the exclusion of the last ten centimeters of the terminal ileum and
      carried out an ileocolic anastomosis. After four weeks of monitoring, blood was
      collected from all animals of the three groups for liver and kidney biochemical
      evaluation (albumin, ALT, AST, direct and indirect bilirubin, alkaline
      phosphatase, cGT, creatinine and urea). RESULTS: there were increased values of
      ALT, AST, direct bilirubin, cGT, creatinine and urea in rats from Group 3 (p <
      0.05). CONCLUSION: ileal exclusion worsened liver and kidney functions in the
      murine model of extrahepatic cholestasis, being disadvantageous as therapeutic
      procedure for cholestatic disorders.

PMID- 24918726
TI  - Effects of splenic allograft in lipid profile of non-splenectomized rats: the
      immune and metabolic role of the "double spleen".
AB  - OBJECTIVE: To elucidate the role of the spleen and splenic allograft in lipid
      control and evaluate its effect on the lipid profile of rats. METHOD: 32 male
      Wistar rats were randomly assigned into four groups: control group (1), total
      splenectomy group (2), splenectomy and implantation of allograft group (3) and
      double spleen group (4). Each group was subdivided into two subgroups: A and B,
      based on the death of the animals after 30 or 120 days of monitoring. The
      procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized
      animals, groups 2 and 3 were donors, respectively, for the animals of groups 3
      and 4. In group 4 the spleen was preserved and the animals received implants from
      the spleens of rats from group 3. The regeneration of splenic tissue was
      evaluated by macroscopic and microscopic analyzes of the grafts and own spleens,
      as well as with measurements of VLDL, HDL, LDL, total cholesterol and
      triglycerides. RESULTS: after 120 days, Group 4 showed levels of total
      cholesterol and LDL lower than the other groups. Group 1 had higher levels of
      lipids. CONCLUSION: The technique of double spleen was effective in the control
      of lipid metabolism, corroborating the function of the spleen as a reserve of
      lipids.

PMID- 24918725
TI  - Liver regeneration with l-glutamine supplemented diet: experimental study in
      rats.
AB  - OBJECTIVE: To assess liver regeneration in rats after 60% hepatectomy with and
      without supplementation of L-glutamine through liver weight changes, laboratory
      parameters and histological study. METHODS: 36 male rats were divided into two
      groups: glutamine group and control group. Each group was subdivided into three
      subgroups, with death in 24h, 72h and seven days. The glutamine group received
      water and standard diet supplemented with L-glutamine, and the control recieved
      0.9% saline. In all subgroups analysis of liver regeneration was made by the Kwon
      formula, study of liver function (AST, ALT, GGT, total bilirubin, indirect and
      indirect bilirubin and albumin) and analysis of cell mitosis by hematoxylin
      eosin. RESULTS: In both groups there was liver regeneration by weight gain. Gamma
      GT increased significantly in the control group (p < 0.05); albumin increased in
      the glutamine group. The other indicators of liver function showed no significant
      differences. Histological analysis at 72h showed a higher number of mitoses in
      the glutamine group, with no differences in other subgroups. CONCLUSION: Diet
      supplementation with L glutamine is beneficial for liver regeneration.

PMID- 24918727
TI  - Effects of low-level laser therapy on wound healing.
AB  - OBJECTIVE: To gather and clarify the actual effects of low-level laser therapy on
      wound healing and its most effective ways of application in human and veterinary
      medicine. METHODS: We searched original articles published in journals between
      the years 2000 and 2011, in Spanish, English, French and Portuguese languages,
      belonging to the following databases: Lilacs, Medline, PubMed and Bireme; Tey
      should contain the methodological description of the experimental design and
      parameters used. RESULTS: doses ranging from 3 to 6 J/cm(2) appear to be more
      effective and doses 10 above J/cm(2) are associated with deleterious effects. The
      wavelengths ranging from 632.8 to 1000 nm remain as those that provide more
      satisfactory results in the wound healing process. CONCLUSION: Low-level laser
      can be safely applied to accelerate the resolution of cutaneous wounds, although
      this fact is closely related to the election of parameters such as dose, time of
      exposure and wavelength.

PMID- 24918728
TI  - Vulvar reconstruction should be performed using gluteal-fold perforator flap
      because of less morbidities and complications.
AB  - The authors present a case of bilateral vulvar defects after abrasion of
      malignant skin neoplasm, reconstructed with a gluteal-fold perforator flap,
      resulting in a successful outcome.

PMID- 24918729
TI  - Low-fidelity bench models for basic surgical skills training during undergraduate
      medical education.
AB  - It is remarkable the reduction in the number of medical students choosing general
      surgery as a career. In this context, new possibilities in the field of surgical
      education should be developed to combat this lack of interest. In this study, a
      program of surgical training based on learning with models of low-fidelity bench
      is designed as a complementary alternative to the various methodologies in the
      teaching of basic surgical skills during medical education, and to develop
      personal interests in career choice.

PMID- 24918730
TI  - Point and Interval Estimators of the Target Dose in Clinical Dose-Finding Studies
      with Active Control.
AB  - In a clinical dose finding study with active control a new drug with several dose
      levels is compared with an active comparator drug. The main focus of such studies
      often lies on the estimation of a target dose that leads to the same efficacy as
      the control. This article investigates the finite sample properties of the
      maximum likelihood estimation of the target dose and compares several approaches
      for constructing corresponding confidence intervals under the assumption of a
      linear dose-response curve and normal error terms. Furthermore, the impact of
      deviations from the model assumptions regarding the error distribution is
      explored. 

PMID- 24918731
TI  - Neutralizing the detrimental effect of glutathione on precious metal catalysts.
AB  - We report our efforts to enable transition-metal catalysis in the presence of
      cellular debris, notably Escherichia coli cell free extracts and cell lysates.
      This challenging goal is hampered by the presence of thiols, mainly present in
      the form of glutathione (GSH), which poison precious metal catalysts. To overcome
      this, we evaluated a selection of oxidizing agents and electrophiles toward their
      potential to neutralize the detrimental effect of GSH on a Ir-based transfer
      hydrogenation catalyst. While the bare catalyst was severely inhibited by
      cellular debris, embedding the organometallic moiety within a host protein led to
      promising results in the presence of some neutralizing agents. In view of its
      complementary to natural enzymes, the asymmetric imine reductase based on the
      incorporation of a biotinylated iridium pianostool complex within streptavidin
      (Sav) isoforms was selected as a model reaction. Compared to purified protein
      samples, we show that pretreatment of cell free extracts and cell lysates
      containing Sav mutants with diamide affords up to >100 TON's and only a modest
      erosion of enantioselectivity. 

PMID- 24918732
TI  - When our vocabulary changed.

PMID- 24918733
TI  - Evaluation of wait times for patients seeking cosmetic and reconstructive breast
      surgery.
AB  - BACKGROUND: Patients seeking cosmetic or reconstructive procedures in plastic
      surgery typically face significant wait times for consultations. Little attention
      has been given to potential disparities in wait times between elective cosmetic
      and reconstructive procedures. In this initial pilot study, we audited a broad
      sample of plastic surgery offices within a single state for wait times in initial
      consultations for both breast reconstruction and breast augmentation. METHODS: A
      sample of board-certified plastic surgeons was audited from the American Society
      of Plastic Surgeons (ASPS) Web site that listed both cosmetic and reconstructive
      breast surgery. Scripted patient telephone calls were made to 67 plastic surgery
      clinics within a single state on May 2012. Two calls separated by 7 days were
      made to each office by the same actor seeking an initial appointment for either
      breast reconstruction or breast augmentation. Wait times were calculated from the
      date of the call until the date of appointment offered. RESULTS: There were 72
      paired calls completed on 36 plastic surgery clinics. Significant disparities in
      appointment wait times existed between elective cosmetic versus reconstructive
      procedures (P = 0.02). Mean wait times for breast reconstruction consultation
      (26.1 days) were significantly longer than mean consultation wait times for
      breast augmentation (20.9 days). Interestingly, 17.9% of offices contacted no
      longer perform certain procedures currently advertised on the ASPS Web site.
      CONCLUSIONS: Disparities exist in access to care between patients seeking
      elective breast augmentation and reconstruction after mastectomy. Patients
      seeking breast augmentation have more rapid access to plastic surgeons. This
      study did not evaluate possible explanations for the observed differences.
      Potential causes may include physician preference and compensation benefits for
      cosmetic procedures.

PMID- 24918734
TI  - Body mass index as a continuous predictor of outcomes after expander-implant
      breast reconstruction.
AB  - BACKGROUND: Studies show that obesity is a risk factor for complications after
      expander/implant breast reconstructions. However, reports vary on the precise
      threshold of body mass index (BMI) as a predictor of heightened risk. We
      endeavored to link BMI as a continuous variable to overall complications in a
      single-surgeon series of expander-implant reconstructions. METHODS: From 399
      patients undergoing expander-implant reconstruction, 551 breasts were stratified
      to normal weight, overweight, and obese groups for analysis and comparison with
      previous studies. Logistic regression was performed to predict changes to risk
      profile per increment of BMI. RESULTS: Complication rates for obese and
      overweight patients were significantly greater than for normal weight patients,
      that is, 21.1% and 24.0% versus 10.4%, respectively (P < 0.005). A unit increase
      in BMI predicted a 5.9% increase in the odds of a complication occurring, and
      7.9% increase in the odds of reconstruction ending in failure. CONCLUSIONS: By
      expanding the analysis of BMI to include patients who do not meet the traditional
      definition of obesity (BMI >= 30 kg/m), we demonstrated that simply overweight
      patients (25 <= BMI < 30 kg/m) had an elevated complication rate. Moreover,
      through regression analysis, we established that BMI as a continuous variable
      predicts outcomes from expander-based breast reconstruction.

PMID- 24918735
TI  - Experience of using cultured epithelial autografts for the extensive burn wounds
      in eight patients.
AB  - In Japan, the cultured epithelial autografts "JACE" was accepted as a health
      insurance adaptation from January 1, 2009. We examined the extensive burn wounds
      in 8 patients by using a combination of autograft and JACE. After debridement, we
      managed the wound bed preparation by using artificial dermis. The wound bed was
      covered with fine tissue 2 weeks after we implanted artificial dermis and
      trafermin was used every day. Meshed 6:1 split-thickness autografts were placed
      onto the recipient wound bed under the JACE. The epidermalization was nearly
      complete within 3 to 4 weeks. RESULTS: A total of 39 patients underwent medical
      treatment of burns. All patients burned more than 30% total body surface area
      (TBSA). We divided them into 2 groups. The control group consisted of 31 patient,
      23 men and 8 women. They underwent operation not using JACE but only autograft.
      The average age of the patients was 59.61 (3.85) years. The TBSA burned in this
      control group was 58.94% (3.89%). Operation times were 2.16 (0.24) hours. The
      overall survival rate was 35.5%. The study group consisted of 8 patients, 5 men
      and 3 women. The average age of the patients was 56.38 (7.04) years. The TBSA
      burned in this study group was 51.63% (4.17%). Operation times were 4.25 (0.59)
      hours, and the overall survival rate in this study group was 87.5%. The average
      take rate of JACE was 80.0% (3.09%) 4 weeks postoperatively. CONCLUSIONS: JACE is
      one of the cultured epithelial autografts. Although we managed the wound bed
      preparation by using artificial dermis instead of cryopreserved cadaver
      allograft, we were able to recognize a good result from grafting JACE on meshed
      6:1 split-thickness autografts. The study group observed a significant difference
      in operation times compared with the control group. However, this treatment
      contributed to reducing the area of the donor site.

PMID- 24918736
TI  - Bilateral propeller flap closure of large meningomyelocele defects.
AB  - BACKGROUND: Meningomyelocele is a defect of the spinal cord, vertebral spine, and
      overlying skin and is the most common form of spinal dysraphism. Multiple methods
      of soft tissue closure for larger myelomeningocele defects have been described,
      including skin grafting, random fasciocutaneous flaps, skin undermining with
      relaxing incisions, and musculocutaneous flaps. Most current methods for closure
      of defects of 8 cm and greater and kyphotic spines usually remains inadequate. In
      this study, we present our clinical experience with a new surgical procedure,
      bilateral propeller (BP) flaps based on dorsal intercostal and lumbar artery
      perforator, for the closure of large thoracolumbar meningomyelocele defects.
      PATIENTS AND METHOD: Between January 2011 and April 2012, 7 newborns (5 males and
      2 females) with thoracolumbar large meningomyelocele were included in the study.
      Six patients had lumbar kyphosis. Myelomeningocele defects with a mean size of
      89.3 cm (range, 58.9-136.8) were closed with BP flaps. RESULTS: All flaps
      survived; hematoma, seroma, wound dehiscence, flap necrosis, or infection was not
      observed. No patients required any surgical revisions. The patients had a follow
      up of 4 to 16 months with a mean of 10 months, and no long-term complications,
      including necrosis of flap edges, wound breakdown, or instability, have been
      apparent in our series. CONCLUSIONS: We believe that the BP flaps represent a
      useful tool in the management of soft tissue defects associated with especially
      kyphotic large thoracolumbar and lumbosacral myelomeningoceles.

PMID- 24918737
TI  - Patient perceptions on physician reimbursement in plastic surgery.
AB  - BACKGROUND: Public perception on physician reimbursement may be that considerable
      payments are received for procedures: a direct contrast to the actual decline. We
      aim to investigate patient perceptions toward plastic surgeon reimbursements from
      insurance companies. METHODS: A survey of 4 common, single-staged procedures was
      administered to 140 patients. Patients were asked for their opinion on current
      insurance company reimbursement fees and what they believed the reimbursement fee
      should be. RESULTS: Eighty-four patients completed the survey. Patients estimated
      physician's reimbursements at 472% to 1061% more for breast reduction, 347% to
      770% for abdominal hernia reconstruction, 372% to 787% for panniculectomy, and
      290% to 628% for mandibular fracture repair. Despite these perceived higher-than
      actual-fee payments, 87% of patients thought reimbursements should still be
      higher. CONCLUSIONS: Patients surveyed overestimated plastic surgery procedure
      fees by 290% to 1061%. Patients should be informed and educated regarding current
      fee schedules to plastic surgeons to correct current misconceptions.

PMID- 24918738
TI  - Use of temporal morphomic indices as a clinically important variable in the
      diagnosis of nonsyndromic craniosynostosis.
AB  - INTRODUCTION: Preoperative computed tomography (CT) evaluation of patients with
      nonsyndromic craniosynostosis (NSC) has focused on the bony cranial vault while
      ignoring the surrounding soft tissues. In this study, we posit that novel CT
      derived temporal muscle and temporal fat pad morphomics (tissue thickness, area,
      and volume) can be used to calculate temporal morphomic indices (TMIs), which are
      unique to each NSC subtype (metopic, coronal, and sagittal) and divergent from
      normal individuals. METHODS: High-throughput image analysis was used to
      reconstruct the 3-dimensional anatomy and quantify a TMI. These steps were
      completed in a semiautomated method using algorithms programmed in MATLAB v13.0.
      Differences in TMI across various craniosynostosis subtypes were assessed using
      Wilcoxon nonparametric tests for both patients with NSC and a control cohort of
      patients with trauma. RESULTS: Using preoperative CT images, we evaluated 117
      children with NSC from the University of Michigan Health System and 50 age
      matched control patients between 1999 and 2011. Results indicate significant
      differences in TMI among the normal and NSC groups, with normal patients having
      significantly higher TMI values than patients with metopic, sagittal, and coronal
      synostosis. In addition, significant differences were found to exist between each
      craniosynostosis category. CONCLUSIONS: Patients with craniosynostosis
      demonstrate diminished temporalis muscle and overlying fat pad volume and
      thickness compared with control patients. The unique changes in temporal
      morphomics presented in this article demonstrate not only that the bony calvaria
      is affected by craniosynostosis but also that there exist quantifiable
      aberrations in the temporalis muscle and temporal fat pad. The methodologies
      described offer a novel methodology to use pre-existing CT scans to glean
      additional preoperative information on the soft tissue characteristics of
      patients with craniosynostosis.

PMID- 24918739
TI  - Chest wall, thymus, and heart vascularized composite allograft proof of concept
      cadaveric model for heart transplantation.
AB  - The use of vascularized composite allografts allows for the reconstruction of
      complex scenarios that previously have required multistaged operations. Heart
      transplantation often follows a series of previous operations leading to chest
      wall deformities and significant mediastinal adhesions that can limit the use of
      larger hearts, making it difficult to find a suitable donor. Further, research
      has shown that the use of vascularized bone marrow and vascularized thymus in
      transplantation potentially prolongs graft survival with decreased
      immunosuppression requirements. The authors propose using a vascularized
      composite allograft of the chest wall consisting of sternum and thymus in
      conjunction with the heart for cardiac transplantation to allow for more
      flexibility from the donor pool, maintain chest wall integrity and physiology,
      and potentially immunoregulate the concomitant solid organ transplant.

PMID- 24918740
TI  - The quality of aesthetic surgery training in plastic surgery residency.

PMID- 24918741
TI  - The quality of aesthetic surgery training in plastic surgery residency: a survey
      among residents in Germany: reply.

PMID- 24918742
TI  - Relative positioning of classical benzodiazepines to the gamma2-subunit of GABAA
      receptors.
AB  - GABAA receptors are the major inhibitory neurotransmitter receptors in the brain.
      Benzodiazepine exert their action via a high affinity-binding site at the
      alpha/gamma subunit interface on some of these receptors. Diazepam has sedative,
      hypnotic, anxiolytic, muscle relaxant, and anticonvulsant effects. It acts by
      potentiating the current evoked by the agonist GABA. Understanding specific
      interaction of benzodiazepines in the binding pocket of different GABAA receptor
      isoforms might help to separate these divergent effects. As a first step, we
      characterized the interaction between diazepam and the major GABAA receptor
      isoform alpha1beta2gamma2. We mutated several amino acid residues on the gamma2
      subunit assumed to be located near or in the benzodiazepine binding pocket
      individually to cysteine and studied the interaction with three ligands that are
      modified with a cysteine-reactive isothiocyanate group (-NCS). When the reactive
      NCS group is in apposition to the cysteine residue this leads to a covalent
      reaction. In this way, three amino acid residues, gamma2Tyr58, gamma2Asn60, and
      gamma2Val190 were located relative to classical benzodiazepines in their binding
      pocket on GABAA receptors. 

PMID- 24918743
TI  - Effects of IL-1beta-Blocking Therapies in Type 2 Diabetes Mellitus: A
      Quantitative Systems Pharmacology Modeling Approach to Explore Underlying
      Mechanisms.
AB  - Recent clinical studies suggest sustained treatment effects of interleukin-1beta
      (IL-1beta)-blocking therapies in type 2 diabetes mellitus. The underlying
      mechanisms of these effects, however, remain underexplored. Using a quantitative
      systems pharmacology modeling approach, we combined ex vivo data of IL-1beta
      effects on beta-cell function and turnover with a disease progression model of
      the long-term interactions between insulin, glucose, and beta-cell mass in type 2
      diabetes mellitus. We then simulated treatment effects of the IL-1 receptor
      antagonist anakinra. The result was a substantial and partly sustained
      symptomatic improvement in beta-cell function, and hence also in HbA1C, fasting
      plasma glucose, and proinsulin-insulin ratio, and a small increase in beta-cell
      mass. We propose that improved beta-cell function, rather than mass, is likely to
      explain the main IL-1beta-blocking effects seen in current clinical data, but
      that improved beta-cell mass might result in disease-modifying effects not
      clearly distinguishable until >1 year after treatment. 

PMID- 24918745
TI  - Burden of seasonal influenza in children with neurodevelopmental conditions.
AB  - BACKGROUND: Studies have identified certain neurologic and neurodevelopmental
      conditions (NNC) as risk factors for severe influenza infection. The Canadian
      National Advisory Committee on Immunization does not currently recognize children
      with NNC as having a high risk of complicated influenza infection unless their
      condition compromises handling of respiratory secretions. We describe the burden
      of influenza in hospitalized children with NNC, focusing on those without
      potential airway compromise. METHODS: Using multi-year surveillance data obtained
      by the Canadian Immunization Monitoring Program, Active (IMPACT), we examined
      presenting signs and symptoms, risk factors and outcomes of children hospitalized
      with seasonal influenza at 12 Canadian pediatric referral centers. Comparisons
      were made between children with various NNC and other medical conditions, with
      and without influenza vaccine indications. The analysis is descriptive with
      selected comparisons made among groups for important indicators of disease
      severity. RESULTS: We identified 1991 children hospitalized with influenza over 5
      seasons: 293 had NNC, 115 of whom did not have airway compromise or another
      vaccine indication. The latter group presented with seizures more frequently than
      those with NNC and a vaccine indication (41.7% vs. 26.4%; P = 0.006) and required
      intensive care unit admission (20.9% vs. 11.8%; P = 0.02) and mechanical
      ventilation (14.8% vs. 4.5%; P < 0.001) more often than children without NNC but
      with a vaccine indication. CONCLUSIONS: The burden of influenza infection in
      children with NNC, even those whose conditions do not obviously compromise
      respiratory function, is significant. All children with NNC should be recognized
      as having a high risk of complicated influenza infection and be targeted to
      receive influenza immunization.

PMID- 24918744
TI  - Association of serum vitamin D with symptoms of depression and anxiety in early
      pregnancy.
AB  - Abstract Objective: To evaluate associations between early pregnancy 25
      hydroxyvitamin D (25[OH]D) concentrations and antepartum depression and anxiety
      symptoms and potential modifiers thereof. MATERIALS AND METHODS: In a pregnancy
      cohort (N=498), we examined cross-sectional associations of early pregnancy
      (mean=15.4 weeks gestation) serum 25[OH]D concentrations and depression and
      anxiety symptoms. Symptoms were measured using Depression, Anxiety, and Stress
      Scales (DASS-21) and Patient Health Questionnaire Depression Module (PHQ-9)
      instruments. Regression models were fit and effect modification by prepregnancy
      body mass index and leisure-time physical activity (LTPA) were assessed using
      interaction terms and stratified analyses. RESULTS AND DISCUSSION: Mean 25[OH]D
      concentration was 34.4 ng/mL. Approximately 12% had "moderate" anxiety (score >=
      10) and depression (score >= 10) symptoms by DASS-21 Anxiety and PHQ-9
      instruments, respectively. A 1 ng/mL lower 25[OH]D was associated with 0.043 and
      0.040 higher DASS-21 Anxiety and PHQ-9 Scores (p-values=0.052 and 0.029,
      respectively). Participants in the lowest quartile of 25[OH]D (<28.9 ng/mL) had
      1.11 higher PHQ-9 scores than those in the highest quartile (>= 39.5 ng/mL,
      p<0.05). However, associations were attenuated and statistically insignificant in
      fully adjusted models. Inverse associations of 25[OH]D with depression symptoms
      were significant among participants who reported no LTPA, but not among women who
      reported any LTPA (interaction p=0.018). CONCLUSIONS: Our study provides modest
      evidence for inverse cross-sectional associations of early pregnancy maternal
      vitamin D concentrations with antepartum depression symptoms. We also observed
      that these associations may be modified by physical activity.

PMID- 24918746
TI  - Rifampin hypersensitivity in a 2-year-old child with successful rapid oral
      desensitization.

PMID- 24918747
TI  - Tuberculous osteomyelitis: a rare form of paradoxical reaction.

PMID- 24918748
TI  - Structure and solid solution properties of Cu-Ag nanoalloys.
AB  - The nanoparticle phase diagram of an immiscible system is studied at the atomic
      level. Cu-Ag clusters with sizes 1000 and 2000 atoms, resulting from a global
      minimum search and belonging to icosahedral and crystalline structural motifs,
      are considered. We present the statistical analysis of the effect of temperature
      on the solubility of the two elements based on Metropolis Monte Carlo importance
      sampling. Our results suggest that the relevance of bulk phase diagrams to
      nanoparticles is limited to cases where the internal stress distribution does not
      deviate very much from uniform (e.g. sufficiently large crystalline clusters). In
      the general case, the principal interdependence between partial phase
      compositions and the overall cluster composition in nanoparticle phase diagrams
      need to be taken into account. 

PMID- 24918749
TI  - Human myocardium releases heat shock protein 27 (HSP27) after global ischemia:
      the proinflammatory effect of extracellular HSP27 through toll-like receptor
      (TLR)-2 and TLR4.
AB  - The myocardial inflammatory response contributes to cardiac functional injury
      associated with heart surgery obligating global ischemia/reperfusion (I/R). Toll
      like receptors (TLRs) play an important role in the mechanism underlying
      myocardial I/R injury. The aim of this study was to examine the release of small
      constitutive heat shock proteins (HSPs) from human and mouse myocardium after
      global ischemia and examine the role of extracellular small HSP in myocardial
      injury. HSP27 release was assessed by enzyme-linked immunosorbent assay. Anti
      HSP27 was applied to evaluate the role of extracellular HSP27 in the postischemic
      inflammatory response and functional injury in mouse hearts. Isolated hearts and
      cultured coronary vascular endothelial cells were exposed to recombinant HSP27 to
      determine its effect on proinflammatory signaling and production of
      proinflammatory mediators. HSP27 levels were markedly elevated in coronary sinus
      blood of patients and in coronary effluent of mouse hearts after global ischemia.
      Neutralizing extracellular HSP27 suppressed myocardial nuclear factor (NF)-kappaB
      activation and interleukin (IL)-6 production and improved cardiac function in
      mouse hearts. Perfusion of HSP27 to mouse hearts induced NF-kappaB activation and
      IL-6 production and depressed contractility. Further, recombinant HSP27 induced
      NF-kappaB phosphorylation and upregulated monocyte chemoattractant protein (MCP)
      1 and intercellular adhesion molecule (ICAM)-1 production in both human and mouse
      coronary vascular endothelial cells. TLR2 knockout (KO) or TLR4 mutation
      abolished NF-kappaB phosphorylation and reduced MCP-1 and ICAM-1 production
      induced by extracellular HSP27 in endothelial cells. In conclusion, these results
      show that the myocardium releases HSP27 after global ischemia and that
      extracellular HSP27 is proinflammatory and contributes to the inflammatory
      mechanism of myocardial functional injury. Both TLR2 and TLR4 are involved in
      mediating the proinflammatory effect of extracellular HSP27. 

PMID- 24918750
TI  - Individual-based ant-plant networks: diurnal-nocturnal structure and species-area
      relationship.
AB  - Despite the importance and increasing knowledge of ecological networks, sampling
      effort and intrapopulation variation has been widely overlooked. Using continuous
      daily sampling of ants visiting three plant species in the Brazilian Neotropical
      savanna, we evaluated for the first time the topological structure over 24 h and
      species-area relationships (based on the number of extrafloral nectaries
      available) in individual-based ant-plant networks. We observed that diurnal and
      nocturnal ant-plant networks exhibited the same pattern of interactions: a nested
      and non-modular pattern and an average level of network specialization. Despite
      the high similarity in the ants' composition between the two collection periods,
      ant species found in the central core of highly interacting species totally
      changed between diurnal and nocturnal sampling for all plant species. In other
      words, this "night-turnover" suggests that the ecological dynamics of these ant
      plant interactions can be temporally partitioned (day and night) at a small
      spatial scale. Thus, it is possible that in some cases processes shaping
      mutualistic networks formed by protective ants and plants may be underestimated
      by diurnal sampling alone. Moreover, we did not observe any effect of the number
      of extrafloral nectaries on ant richness and their foraging on such plants in any
      of the studied ant-plant networks. We hypothesize that competitively superior
      ants could monopolize individual plants and allow the coexistence of only a few
      other ant species, however, other alternative hypotheses are also discussed.
      Thus, sampling period and species-area relationship produces basic information
      that increases our confidence in how individual-based ant-plant networks are
      structured, and the need to consider nocturnal records in ant-plant network
      sampling design so as to decrease inappropriate inferences. 

PMID- 24918751
TI  - A comparison of facial color pattern and gazing behavior in canid species
      suggests gaze communication in gray wolves (Canis lupus).
AB  - As facial color pattern around the eyes has been suggested to serve various
      adaptive functions related to the gaze signal, we compared the patterns among 25
      canid species, focusing on the gaze signal, to estimate the function of facial
      color pattern in these species. The facial color patterns of the studied species
      could be categorized into the following three types based on contrast indices
      relating to the gaze signal: A-type (both pupil position in the eye outline and
      eye position in the face are clear), B-type (only the eye position is clear), and
      C-type (both the pupil and eye position are unclear). A-type faces with light
      colored irises were observed in most studied species of the wolf-like clade and
      some of the red fox-like clade. A-type faces tended to be observed in species
      living in family groups all year-round, whereas B-type faces tended to be seen in
      solo/pair-living species. The duration of gazing behavior during which the facial
      gaze-signal is displayed to the other individual was longest in gray wolves with
      typical A-type faces, of intermediate length in fennec foxes with typical B-type
      faces, and shortest in bush dogs with typical C-type faces. These results suggest
      that the facial color pattern of canid species is related to their gaze
      communication and that canids with A-type faces, especially gray wolves, use the
      gaze signal in conspecific communication. 

PMID- 24918752
TI  - A comparison of the ability of levels of urinary biomarker proteins and exosomal
      mRNA to predict outcomes after renal transplantation.
AB  - BACKGROUND: mRNA for biomarkers of kidney injury extracted from urinary exosomes
      may reflect or predict levels of the corresponding protein after transplantation
      and clinical outcomes. METHODS: Urinary exosomes were isolated from patients
      following renal transplantation, from healthy controls, and patients with CKD.
      Expression of exosomal mRNA for the injury biomarkers neutrophil gelatinase
      associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1
      (KIM-1), and cystatin C was compared with the concentrations of corresponding
      urinary proteins, 18S RNA and serum creatinine. RESULTS: All biomarker protein
      concentrations increased after transplantation, and urinary NGAL and IL-18 at 24
      and 168 h correlated with the day 7 creatinine reduction ratio (CRR). Exosomal18S
      RNA increased after transplantation, but exosomal mRNA for NGAL, IL-18 and
      cystatin C did not correlate with the day 7 CRR, or urinary biomarker
      concentrations at any time after transplantation. Exosomal NGAL mRNA was lower 4
      h after transplantation than in control exosomes. In contrast, exosomal mRNA for
      cystatin C was unchanged after transplantation and in CKD, although urinary
      cystatin C temporarily increased following transplantation. Urinary KIM-1
      increased after transplantation, but exosomal mRNA for KIM-1 remained
      undetectable. In CKD 18S RNA was raised, and exosomal mRNA for NGAL, IL-18 and
      cystatin C was detected in all patients. While urinary NGAL was greater in CKD
      than control subjects, exosomal NGAL mRNA was unchanged. Exosomal IL-18 mRNA was
      increased in CKD, but not IL-18 protein. CONCLUSIONS: After renal
      transplantation, urinary NGAL and IL-18 levels reflect the day 7 CRR. However,
      while mRNA for these biomarkers is present in exosomes, their levels do not
      reflect or predict urinary biomarker levels or the CRR. This likely reflects the
      fact that packaging of mRNA in exosomes is selective, and is not necessarily
      representative of mRNA in the parent cells responsible for biomarker production.

PMID- 24918753
TI  - Alpha-2-glycoprotein 1(AZGP1) regulates biological behaviors of LoVo cells by
      down-regulating mTOR signaling pathway and endogenous fatty acid synthesis.
AB  - AZGP1 is a multifaceted protein associated with lipid mobilization, a process
      that is regulated by FASN and other metabolic pathways such as mTOR signaling.
      The active mTOR signaling pathway has been found to be involved in a variety of
      tumors. However, it remains unclear whether it is involved in the regulation of
      AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human
      colorectal cancer cell line (LoVo) with a low expression of AZGP1. The expression
      of AZGP1, FASN, eIF4E, p-mTOR, p-S6,and S6K1 were measured by Western blot
      analysis, and target genes were detected by RT-PCR. Cell proliferation was
      studied using the MTT and colony formation assays. The analysis of apoptosis and
      the cell cycle phase were assessed by flow cytometry. The capacity of cell
      migration was investigated using the transwell migration assay. We found that the
      expression of AZGP1 was up-regulated while the expression of FASN, eIF4E, p-mTOR,
      p-S6, and S6K1 were down-regulated in LoVo cells after AZGP1 was expressed. The
      proliferation of malignant cells was reduced in AZGP1-overexpression cells, which
      is consistent with an increased in the G2-arrest and apoptosis rate. Furthermore,
      the migration of AZGP1-overexpression cells was decreased. The overexpression of
      AZGP1 suppressed the activation of the mTOR pathway and endogenous FASN-regulated
      fatty acid synthesis, mitigating the malignant phenotype of LoVo cells. Herein,
      we provide evidence that AZGP1 may constitute a novel tumor suppressor for LoVo
      colorectal cancer cells. 

PMID- 24918754
TI  - Definite differences between in vitro actin-myosin sliding and muscle contraction
      as revealed using antibodies to myosin head.
AB  - Muscle contraction results from attachment-detachment cycles between myosin heads
      extending from myosin filaments and actin filaments. It is generally believed
      that a myosin head first attaches to actin, undergoes conformational changes to
      produce force and motion in muscle, and then detaches from actin. Despite
      extensive studies, the molecular mechanism of myosin head conformational changes
      still remains to be a matter for debate and speculation. The myosin head consists
      of catalytic (CAD), converter (CVD) and lever arm (LD) domains. To give
      information about the role of these domains in the myosin head performance, we
      have examined the effect of three site-directed antibodies to the myosin head on
      in vitro ATP-dependent actin-myosin sliding and Ca2+-activated contraction of
      muscle fibers. Antibody 1, attaching to junctional peptide between 50K and 20K
      heavy chain segments in the CAD, exhibited appreciable effects neither on in
      vitro actin-myosin sliding nor muscle fiber contraction. Since antibody 1 covers
      actin-binding sites of the CAD, one interpretation of this result is that rigor
      actin-myosin linkage is absent or at most a transient intermediate in
      physiological actin-myosin cycling. Antibody 2, attaching to reactive lysine
      residue in the CVD, showed a marked inhibitory effect on in vitro actin-myosin
      sliding without changing actin-activated myosin head (S1) ATPase activity, while
      it showed no appreciable effect on muscle contraction. Antibody 3, attaching to
      two peptides of regulatory light chains in the LD, had no significant effect on
      in vitro actin-myosin sliding, while it reduced force development in muscle
      fibers without changing MgATPase activity. The above definite differences in the
      effect of antibodies 2 and 3 between in vitro actin-myosin sliding and muscle
      contraction can be explained by difference in experimental conditions; in the
      former, myosin heads are randomly oriented on a glass surface, while in the
      latter myosin heads are regularly arranged within filament-lattice structures. 

PMID- 24918755
TI  - Evaluation of Minnesota and Illinois hospital respiratory protection programs and
      health care worker respirator use.
AB  - The objective of this study was to assess respiratory protection programs for
      aerosol-transmissible diseases in acute care hospitals for conformance with
      regulatory requirements and public health guidelines. Twenty-eight representative
      hospitals were selected by size, location, and ownership in Minnesota and
      Illinois. Interviews were conducted with 363 health care workers and 171 managers
      from high-risk departments. Written programs from each hospital were reviewed for
      required elements. Seventy-seven health care workers were observed donning and
      doffing a FFR. The most serious deficiency in many written programs was failure
      to identify a program administrator. Most written programs lacked adequate
      details about medical evaluation, fit-testing, and training and did not include a
      comprehensive risk assessment for aerosol transmissible diseases; tuberculosis
      was often the only pathogen addressed. Employees with the highest probability of
      tuberculosis exposure were most likely to pick a respirator for close contact,
      but higher levels of respiratory protection were rarely selected for aerosol
      generating procedures. Surgical masks were most commonly selected for close
      contact with droplet disease- or influenza-infected patients; better protection
      (e.g., respirator) was rarely selected for higher-risk exposures. Most of the
      observed health care workers had access to a NIOSH-certified N95 FFR, properly
      positioned the facepiece, and formed the nose clip. The most frequent
      deficiencies were failure to correctly place straps, perform a user seal check,
      and remove the respirator using straps. 

PMID- 24918756
TI  - Involvement of increased endogenous asymmetric dimethylarginine in the hepatic
      endoplasmic reticulum stress of type 2 diabetic rats.
AB  - OBJECTIVE: Increasing evidence suggested that endoplasmic reticulum (ER) stress
      contributes to insulin resistance, which plays an important role in the
      development of type 2 diabetes mellitus (T2DM). Accumulation of endogenous nitric
      oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA), is associated
      with insulin resistance, T2DM, and diabetic cardiovascular complications,
      although the mechanisms have not been elucidated. This study was to determine
      whether elevated endogenous ADMA is involved in hepatic ER stress of type 2
      diabetic rats, verify their causal relationship, and elucidate the potential
      mechanism underlying ADMA induced ER stress in rat hepatocytes. METHODS:
      Immunoglobulin binding protein (Bip) transcription, eukaryotic initiation factor
      2alpha kinase (eIF2alpha) phosphorylation, X box-binding protein-1 (XBP-1) mRNA
      splicing and C/EBP homologues protein (CHOP) expression were measured to reflect
      ER stress. Contents of ADMA and nitrite/nitrate as well as activities or
      expression of NOS and dimethylarginine dimethylaminohydrolase (DDAH) were
      detected to show the changes in DDAH/ADMA/NOS/NO pathway. The lipid peroxidation
      product malondialdehyde content and antioxidant enzyme superoxide dismutase
      activity were analyzed to evaluate oxidative stress. RESULTS: ER stress was
      provoked in the liver of type 2 diabetic rats, as expressed by increases of Bip
      transcription, eIF2alpha phosphorylation, XBP-1 splicing and CHOP expression, all
      of which were in parallel with the elevation of serum ADMA, suppression of NO
      generation, NOS and DDAH activities in the liver. Exposure of hepatocytes to ADMA
      or hydrogen peroxide also induced ER stress, which was associated with the
      inhibition of NO production and increase of oxidative stress. Treatment of
      hepatocytes with antioxidant pyrrolidine dithiocarbamate not only decreased ADMA
      induced oxidative stress and inhibition of NO production but also reduced ADMA
      triggered ER stress. CONCLUSIONS: These results indicate that increased
      endogenous ADMA contributes to hepatic ER stress in type 2 diabetic rats, and the
      mechanism underlying ADMA-induced ER stress may relate to oxidative stress via
      NOS uncoupling.

PMID- 24918757
TI  - Creating a charter of collaboration for international university partnerships:
      the Elmina Declaration for Human Resources for Health.
AB  - The potential of international academic partnerships to build global capacity is
      critical in efforts to improve health in poorer countries. Academic
      collaborations, however, are challenged by distance, communication issues,
      cultural differences, and historical context. The Collaborative Health Alliance
      for Reshaping Training, Education, and Research project (funded by the Bill and
      Melinda Gates Foundation and implemented through academic medicine and public
      health and governmental institutions in Michigan and Ghana) took a prospective
      approach to address these issues. The project had four objectives: to create a
      "charter for collaboration" (CFC), to improve data-driven policy making, to
      enhance health care provider education, and to increase research capacity. The
      goal of the CFC was to establish principles to guide the course of the technical
      work. All participants participated at an initial conference in Elmina, Ghana.
      Nine months later, the CFC had been revised and adopted. A qualitative
      investigation of the CFC's effects identified three themes: the CFC's unique
      value, the influence of the process of creating the CFC on patterns of
      communication, and the creation of a context for research and collaboration.
      Creating the CFC established a context in which implementing technical
      interventions became an opportunity for dialogue and developing a mutually
      beneficial partnership. To increase the likelihood that research results would be
      translated into policy reforms, the CFC made explicit the opportunities,
      potential problems, and institutional barriers to be overcome. The process of
      creating a CFC and the resulting document define a new standard in academic and
      governmental partnerships. 

PMID- 24918758
TI  - AM last page: the urgency of physician workforce diversity.

PMID- 24918759
TI  - SNAPPS-Plus: an educational prescription for students to facilitate formulating
      and answering clinical questions.
AB  - PURPOSE: To analyze the content and quality of PICO-formatted questions (Patient
      Intervention-Comparison-Outcome), and subsequent answers, from students'
      educational prescriptions added to the final SNAPPS Select step (SNAPPS-Plus).
      METHOD: Internal medicine clerkship students at the University of Minnesota
      Medical Center were instructed to use educational prescriptions to complement
      their bedside SNAPPS case presentations from 2006 to 2010. Educational
      prescriptions were collected from all eligible students and coded for topic of
      uncertainty, PICO conformity score, presence of answer, and quality of answer.
      Spearman rank-order correlation coefficient was used to compare ordinal
      variables, Kruskal-Wallis test to compare distribution of PICO scores between
      groups, and McNemar exact test to test for association between higher PICO scores
      and presence of an answer. RESULTS: A total of 191 education prescriptions were
      coded from 191 eligible students, of which 190 (99%) included a question and 176
      (93%, 176/190) an answer. Therapy questions constituted 59% (112/190) of the
      student-generated questions; 19% (37/190) were related to making a diagnosis.
      Three-fifths of the questions (61%, 116/190) were scored either 7 or 8 on the 8
      point PICO conformity scale. The quality of answers varied, with 37% (71/190)
      meeting all criteria for high quality. There was a positive correlation between
      the PICO conformity score and the quality of the answers (Spearman rank-order
      correlation coefficient = 0.726; P < .001). CONCLUSIONS: The SNAPPS-Plus
      technique was easily integrated into the inpatient clerkship structure and
      guaranteed that virtually every case presentation following this model had a well
      formulated question and answer.

PMID- 24918760
TI  - Interprofessional global health education in a cosmopolitan community of North
      America: the iCHEE experience.
AB  - PROBLEM: The rapidly diversifying population of North America has disparate
      health needs that are addressed by creative, community-based training of health
      professions students. APPROACH: The authors report five years (2008-2012) of
      experience implementing a novel interprofessional Community Health and Education
      Exchange (iCHEE) elective course for dental, medical, nursing, nutrition,
      pharmacy, physician assistant, and public health students at Oregon Health &
      Science University (OHSU). This pioneering interprofessional course was created
      by the OHSU Global Health Center and is offered in fall, winter, and spring
      quarters. Students interact with individual clients drawn from community centers
      supporting refugees, recent immigrants, and other underserved people. In addition
      to health concerns, clients are encouraged to share backgrounds and experiences
      with student teams. Clients receive guidance on nutrition, exercise,
      pharmaceuticals, and accessible health services. Student teams perform a
      noninvasive health check on clients with the assistance of faculty mentors who,
      on finding a physical or mental health issue, refer the client from the
      educational setting to an appropriate health care facility. OUTCOMES: In addition
      to supporting health promotion and early intervention for medically underserved
      people, students reported gaining valuable cross-cultural knowledge,
      understanding, and experience from clients. Students also appreciated the value
      of diverse skills and knowledge available in their multidisciplinary teams.
      Through the end of 2012, over 300 health professions students worked with
      approximately 1,200 clients to complete the iCHEE course. NEXT STEPS: The iCHEE
      model should prove helpful in preparing health professions students at other
      institutions to understand and serve diverse populations.

PMID- 24918761
TI  - Increasing women in leadership in global health.
AB  - Globally, women experience a disproportionate burden of disease and death due to
      inequities in access to basic health care, nutrition, and education. In the face
      of this disparity, it is striking that leadership in the field of global health
      is highly skewed towards men and that global health organizations neglect the
      issue of gender equality in their own leadership. Randomized trials demonstrate
      that women in leadership positions in governmental organizations implement
      different policies than men and that these policies are more supportive of women
      and children. Other studies show that proactive interventions to increase the
      proportion of women in leadership positions within businesses or government can
      be successful. Therefore, the authors assert that increasing female leadership in
      global health is both feasible and a fundamental step towards addressing the
      problem of women's health. In this Perspective, the authors contrast the high
      proportion of young female trainees who are interested in academic global health
      early in their careers with the low numbers of women successfully rising to
      global health leadership roles. The authors subsequently explore reasons for
      female attrition from the field of global health and offer practical strategies
      for closing the gender gap in global health leadership. The authors propose
      solutions aimed to promote female leaders from both resource-wealthy and resource
      poor countries, including leadership training grants, mentorship from female
      leaders in global professions, strengthening health education in resource-poor
      countries, research-enabling grants, and altering institutional policies to
      support women choosing a global health career path. 

PMID- 24918762
TI  - Global faculty development: lessons learned from the Foundation for Advancement
      of International Medical Education and Research (FAIMER) initiatives.
AB  - Foundation for Advancement of International Medical Education and Research
      (FAIMER) faculty development programs have operated since 2001 and are designed
      to overcome many of the challenges inherent in global health collaborations,
      including alignment with local needs, avoiding persistent dependency, and
      development of trust. FAIMER fellowship programs, developed for midcareer faculty
      members in all health professions from around the world, share goals of
      strengthening knowledge and skills in education leadership, education methods,
      and project management and evaluation. Building community is another explicit
      goal that allows participants to support and learn from each other.The author
      recommends several practices for successful international collaborations based on
      13 years of experience with FAIMER fellowships. These include using authentic
      education projects to maintain alignment with local needs and apply newly
      acquired knowledge and skills, teaching leadership across cultures with careful
      communication and adaptation of concepts to local environments, cultivating a
      strong field of health professions education to promote diffusion of ideas and
      advocate for policy change, intentionally promoting field development and
      leadership to reduce dependency, giving generously of time and resources,
      learning from others as much as teaching others, and recognizing that effective
      partnerships revolve around personal relationships to build trust. These
      strategies have enabled the FAIMER fellowship programs to stay aligned with local
      needs, reduce dependency, and maintain trust. 

PMID- 24918763
TI  - Storage of human biospecimens: selection of the optimal storage temperature.
AB  - Millions of biological samples are currently kept at low tempertures in
      cryobanks/biorepositories for long-term storage. The quality of the biospecimen
      when thawed, however, is not only determined by processing of the biospecimen but
      the storage conditions as well. The overall objective of this article is to
      describe the scientific basis for selecting a storage temperature for a
      biospecimen based on current scientific understanding. To that end, this article
      reviews some physical basics of the temperature, nucleation, and ice crystal
      growth present in biological samples stored at low temperatures (-20 degrees C to
      -196 degrees C), and our current understanding of the role of temperature on the
      activity of degradative molecules present in biospecimens. The scientific
      literature relevant to the stability of specific biomarkers in human fluid, cell,
      and tissue biospecimens is also summarized for the range of temperatures between 
      20 degrees C to -196 degrees C. These studies demonstrate the importance of
      storage temperature on the stability of critical biomarkers for fluid, cell, and
      tissue biospecimens.

PMID- 24918764
TI  - HIVE-hexagon: high-performance, parallelized sequence alignment for next
      generation sequencing data analysis.
AB  - Due to the size of Next-Generation Sequencing data, the computational challenge
      of sequence alignment has been vast. Inexact alignments can take up to 90% of
      total CPU time in bioinformatics pipelines. High-performance Integrated Virtual
      Environment (HIVE), a cloud-based environment optimized for storage and analysis
      of extra-large data, presents an algorithmic solution: the HIVE-hexagon DNA
      sequence aligner. HIVE-hexagon implements novel approaches to exploit both
      characteristics of sequence space and CPU, RAM and Input/Output (I/O)
      architecture to quickly compute accurate alignments. Key components of HIVE
      hexagon include non-redundification and sorting of sequences; floating diagonals
      of linearized dynamic programming matrices; and consideration of cross-similarity
      to minimize computations. AVAILABILITY: https://hive.biochemistry.gwu.edu/hive/

PMID- 24918767
TI  - Cost-effectiveness of a WOC advanced practice nurse in the acute care and
      outpatient setting.
AB  - Increasing numbers of advanced practice nurses who practice within the WOC
      specialty are challenged by the need to justify their role by demonstrating
      clinical and fiscal benefits to the employing agency. This View From Here column
      describes the steps I took while completing such an analysis for a position for a
      nurse practitioner with WOC certification in upstate New York. 

PMID- 24918765
TI  - Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade
      laryngeal neoplasia.
AB  - Patients with recurrent respiratory papillomatosis (RRP) in Norway treated
      between 1987 and 2009 were recruited to this cohort study. They were followed
      from disease onset and data recorded until January 2012. Here, we describe the
      distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple
      HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory
      tract invasive carcinoma in a large cohort of patients with RRP. We also examined
      whether HPV genotype, gender, age or clinical course are risk factors for this
      development. Clinical records and histological specimens were reviewed. Using
      formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by
      quantitative polymerase chain reaction assays identifying 15 HPV types. HPV
      negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were
      available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV
      DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive,
      comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases.
      Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11
      was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative
      specimens revealed HPV 8 in one case. In total, 39/221 patients developed high
      grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory
      tract (six patients with laryngeal carcinoma and two patients with lung
      carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV
      negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99), as well as
      respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91). In summary, the
      majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies
      occurred more frequently in adult-onset patients, and were associated with an
      increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

PMID- 24918766
TI  - Audio-tactile integration in congenitally and late deaf cochlear implant users.
AB  - Several studies conducted in mammals and humans have shown that multisensory
      processing may be impaired following congenital sensory loss and in particular if
      no experience is achieved within specific early developmental time windows known
      as sensitive periods. In this study we investigated whether basic multisensory
      abilities are impaired in hearing-restored individuals with deafness acquired at
      different stages of development. To this aim, we tested congenitally and late
      deaf cochlear implant (CI) recipients, age-matched with two groups of hearing
      controls, on an audio-tactile redundancy paradigm, in which reaction times to
      unimodal and crossmodal redundant signals were measured. Our results showed that
      both congenitally and late deaf CI recipients were able to integrate audio
      tactile stimuli, suggesting that congenital and acquired deafness does not
      prevent the development and recovery of basic multisensory processing. However,
      we found that congenitally deaf CI recipients had a lower multisensory gain
      compared to their matched controls, which may be explained by their faster
      responses to tactile stimuli. We discuss this finding in the context of
      reorganisation of the sensory systems following sensory loss and the possibility
      that these changes cannot be "rewired" through auditory reafferentation. 

PMID- 24918768
TI  - A fungal conserved gene from the basidiomycete Hebeloma cylindrosporum is
      essential for efficient ectomycorrhiza formation.
AB  - We used Agrobacterium-mediated insertional mutagenesis to identify genes in the
      ectomycorrhizal fungus Hebeloma cylindrosporum that are essential for efficient
      mycorrhiza formation. One of the mutants presented a dramatically reduced ability
      to form ectomycorrhizas when grown in the presence of Pinus pinaster. It failed
      to form mycorrhizas in the presence of glucose at 0.5 g liter(-1), a condition
      favorable for mycorrhiza formation by the wild-type strain. However, it formed
      few mycorrhizas when glucose was replaced by fructose or when glucose
      concentration was increased to 1 g liter(-1). Scanning electron microscopy
      examination of these mycorrhizas revealed that this mutant was unable to
      differentiate true fungal sheath and Hartig net. Molecular analyses showed that
      the single-copy disrupting T-DNA was integrated 6,884 bp downstream from the
      start codon, of an open reading frame potentially encoding a 3,096-amino-acid
      long protein. This gene, which we named HcMycE1, has orthologs in numerous fungi
      as well as different other eukaryotic microorganisms. RNAi inactivation of
      HcMycE1 in the wild-type strain also led to a mycorrhizal defect, demonstrating
      that the nonmycorrhizal phenotype of the mutant was due to mutagenic T-DNA
      integration in HcMycE1. In the wild-type strain colonizing P. pinaster roots,
      HcMycE1 was transiently upregulated before symbiotic structure differentiation.
      Together with the inability of the mutant to differentiate these structures, this
      suggests that HcMycE1 plays a crucial role upstream of the fungal sheath and
      Hartig net differentiation. This study provides the first characterization of a
      fungal mutant altered in mycorrhizal ability. 

PMID- 24918771
TI  - Lipid-modified polyethylenimine-mediated DNA attraction evaluated by molecular
      dynamics simulations.
AB  - The effect of lipid modification on polyethylenimine (PEI)-mediated DNA
      attraction was studied by performing umbrella sampling molecular dynamics
      simulations that involved PEIs modified with three different types of lipids:
      oleic acid (OA), linoleic acid (LA), and caprylic acid (CA). The potential of
      mean force between two DNA molecules in the presence of these lipid-modified PEIs
      was calculated using the weighted histogram analysis method, and it predicted the
      stability and size of the DNA aggregate. When compared to native PEI, lipid
      modification was found to enhance the stability of DNA aggregation in the case of
      long lipids (LA and OA) but reduce the stability in the case of a short lipid
      (CA). In addition, LA-substituted PEI was shown to form stronger DNA aggregate
      than OA-substituted PEI, which correlates positively with previous experimental
      observations. 

PMID- 24918769
TI  - Discovery and characterization of distinct simian pegiviruses in three wild
      African Old World monkey species.
AB  - Within the Flaviviridae, the recently designated genus Pegivirus has expanded
      greatly due to new discoveries in bats, horses, and rodents. Here we report the
      discovery and characterization of three simian pegiviruses (SPgV) that resemble
      human pegivirus (HPgV) and infect red colobus monkeys (Procolobus tephrosceles),
      red-tailed guenons (Cercopithecus ascanius) and an olive baboon (Papio anubis).
      We have designated these viruses SPgVkrc, SPgVkrtg and SPgVkbab, reflecting their
      host species' common names, which include reference to their location of origin
      in Kibale National Park, Uganda. SPgVkrc and SPgVkrtg were detected in 47%
      (28/60) of red colobus and 42% (5/12) red-tailed guenons, respectively, while
      SPgVkbab infection was observed in 1 of 23 olive baboons tested. Infections were
      not associated with any apparent disease, despite the generally high viral loads
      observed for each variant. These viruses were monophyletic and equally divergent
      from HPgV and pegiviruses previously identified in chimpanzees (SPgVcpz).
      Overall, the high degree of conservation of genetic features among the novel
      SPgVs, HPgV and SPgVcpz suggests conservation of function among these closely
      related viruses. Our study describes the first primate pegiviruses detected in
      Old World monkeys, expanding the known genetic diversity and host range of
      pegiviruses and providing insight into the natural history of this genus. 

PMID- 24918770
TI  - R-spondin 3 regulates dorsoventral and anteroposterior patterning by antagonizing
      Wnt/beta-catenin signaling in zebrafish embryos.
AB  - The Wnt/beta-catenin or canonical Wnt signaling pathway plays fundamental roles
      in early development and in maintaining adult tissue homeostasis. R-spondin 3
      (Rspo3) is a secreted protein that has been implicated in activating the Wnt/beta
      catenin signaling in amphibians and mammals. Here we report that zebrafish Rspo3
      plays a negative role in regulating the zygotic Wnt/beta-catenin signaling.
      Zebrafish Rspo3 has a unique domain structure. It contains a third furin-like
      (FU3) domain. This FU3 is present in other four ray-finned fish species studied
      but not in elephant shark. In zebrafish, rspo3 mRNA is maternally deposited and
      has a ubiquitous expression in early embryonic stages. After 12 hpf, its
      expression becomes tissue-specific. Forced expression of rspo3 promotes
      dorsoanterior patterning and increases the expression of dorsal and anterior
      marker genes. Knockdown of rspo3 increases ventral-posterior development and
      stimulates ventral and posterior marker genes expression. Forced expression of
      rspo3 abolishes exogenous Wnt3a action and reduces the endogenous Wnt signaling
      activity. Knockdown of rspo3 results in increased Wnt/beta-catenin signaling
      activity. Further analyses indicate that Rspo3 does not promote maternal Wnt
      signaling. Human RSPO3 has similar action when tested in zebrafish embryos. These
      results suggest that Rspo3 regulates dorsoventral and anteroposterior patterning
      by negatively regulating the zygotic Wnt/beta-catenin signaling in zebrafish
      embryos. 

PMID- 24918772
TI  - Differential neutralizing activities of a single domain camelid antibody (VHH)
      specific for ricin toxin's binding subunit (RTB).
AB  - Ricin, a member of the A-B family of ribosome-inactivating proteins, is
      classified as a Select Toxin by the Centers for Disease Control and Prevention
      because of its potential use as a biothreat agent. In an effort to engineer
      therapeutics for ricin, we recently produced a collection of alpaca-derived,
      heavy-chain only antibody VH domains (VHH or "nanobody") specific for ricin's
      enzymatic (RTA) and binding (RTB) subunits. We reported that one particular RTB
      specific VHH, RTB-B7, when covalently linked via a peptide spacer to different
      RTA-specific VHHs, resulted in heterodimers like VHH D10/B7 that were capable of
      passively protecting mice against a lethal dose challenge with ricin. However,
      RTB-B7 itself, when mixed with ricin at a 1 ? 10 toxin:antibody ratio did not
      afford any protection in vivo, even though it had demonstrable toxin-neutralizing
      activity in vitro. To better define the specific attributes of antibodies
      associated with ricin neutralization in vitro and in vivo, we undertook a more
      thorough characterization of RTB-B7. We report that RTB-B7, even at 100-fold
      molar excess (toxin:antibody) was unable to alter the toxicity of ricin in a
      mouse model. On the other hand, in two well-established cytotoxicity assays, RTB
      B7 neutralized ricin with a 50% inhibitory concentration (IC50) that was
      equivalent to that of 24B11, a well-characterized and potent RTB-specific murine
      monoclonal antibody. In fact, RTB-B7 and 24B11 were virtually identical when
      compared across a series of in vitro assays, including adherence to and
      neutralization of ricin after the toxin was pre-bound to cell surface receptors.
      RTB-B7 differed from both 24B11 and VHH D10/B7 in that it was relatively less
      effective at blocking ricin attachment to receptors on host cells and was not
      able to form high molecular weight toxin:antibody complexes in solution. Whether
      either of these activities is important in ricin toxin neutralizing activity in
      vivo remains to be determined.

PMID- 24918773
TI  - Rich structural chemistry in scandium selenium/tellurium oxides: mixed-valent
      selenite-selenates, Sc2(SeO3)2(SeO4) and Sc2(TeO3)(SeO3)(SeO4), and ternary
      tellurite, Sc2(TeO3)3.
AB  - Both single crystals and pure bulk phases of three new scandium
      selenium/tellurium oxides, Sc2(SeO3)2(SeO4), Sc2(TeO3)(SeO3)(SeO4), and
      Sc2(TeO3)3, have been synthesized through hydrothermal and solid-state reactions.
      X-ray diffractions were used to determine the structures and confirm the phase
      purities of the reported materials. Isostructural Sc2(SeO3)2(SeO4) and
      Sc2(TeO3)(SeO3)(SeO4) reveal three-dimensional frameworks with ScO7 pentagonal
      bipyramids, SeO3 (and TeO3) trigonal pyramids, and SeO4 tetrahedra. A novel
      ternary scandium tellurite, Sc2(TeO3)3, also shows a three-dimensional framework
      that is composed of ScO6 octahedra, ScO7-capped octahedra, and TeO3 trigonal
      pyramids. All three materials accommodate local asymmetric coordination moieties
      owing to the lone pairs on Se(4+) and Te(4+) cations. The effect of coordination
      environments of constituent cations on the frameworks, dimensionalities, and
      centricities of products is discussed. Thorough characterizations including
      elemental analyses, infrared and UV-vis diffuse reflectance spectroscopies,
      thermal analyses, and dipole moment calculations for the reported materials are
      reported. Crystal data: Sc2(SeO3)2(SeO4), monoclinic, space group P21/c (No. 14),
      a = 6.5294(2) A, b = 10.8557(4) A, c = 12.6281(6) A, beta = 103.543(3) degrees ,
      V = 870.21(6) A(3), and Z = 4; Sc2(TeO3)(SeO3)(SeO4), monoclinic, space group
      P21/c (No. 14), a = 6.5345(12) A, b = 10.970(2) A, c = 12.559(2) A, beta =
      102.699(10) degrees , V = 878.3(6) A(3), and Z = 4; Sc2(TeO3)3, monoclinic, space
      group P21/n (No. 14), a = 5.2345(3) A, b = 24.3958(15) A, c = 6.8636(4) A, beta =
      106.948(2) degrees , V = 838.42(9) A(3), and Z = 4. 

PMID- 24918774
TI  - Clinical performance metrics of 3D digital breast tomosynthesis compared with 2D
      digital mammography for breast cancer screening in community practice.
AB  - OBJECTIVE: The objective of our study was to assess the clinical performance of
      combined 2D-3D digital breast tomosynthesis (DBT), referred to as "3D DBT,"
      compared with 2D digital mammography (DM) alone for screening mammography in a
      community-based radiology practice. MATERIALS AND METHODS: Performance outcomes
      measures were assessed for 14 radiologists who interpreted more than 500
      screening mammography 3D DBT studies after the initiation of tomosynthesis.
      Outcomes from screening mammography during the study period between August 9,
      2011, and November 30, 2012, using 3D DBT (n = 23,149 patients) versus 2D DM (n =
      54,684 patients) were compared. RESULTS: For patients screened with 3D DBT, the
      relative change in recall rate was 16.1% lower than for patients screened with 2D
      DM (p > 0.0001). The overall cancer detection rate (CDR), expressed as number of
      cancers per 1000 patients screened, was 28.6% greater (p = 0.035) for 3D DBT
      (6.3/1000) compared with 2D DM (4.9/1000). The CDR for invasive cancers with 3D
      DBT (4.6/1000) was 43.8% higher (p = 0.0056) than with 2D DM (3.2/1000). The
      positive predictive value for recalls from screening (PPV1) was 53.3% greater (p
      = 0.0003) for 3D DBT (4.6%) compared with 2D DM (3.0%). No significant difference
      in the positive predictive value for biopsy (PPV3) was found for 3D DBT versus 2D
      DM (22.8% and 23.8%, respectively) (p = 0.696). CONCLUSION: In community-based
      radiology practice, mammography screening with 3D DBT yielded lower recall rates,
      an increased CDR for cancer overall, and an increased CDR for invasive cancer
      compared with 2D DM. The PPV1 was significantly greater in the group screened
      using 3D DBT.

PMID- 24918775
TI  - Maternal high-fat diet worsens memory deficits in the triple-transgenic (3xTgAD)
      mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is not normally diagnosed until later in life, although
      evidence suggests that the disease starts at a much earlier age. Risk factors for
      AD, such as diabetes, hypertension and obesity, are known to have their affects
      during mid-life, though events very early in life, including maternal over
      nutrition, can predispose offspring to develop these conditions. This study
      tested whether over-nutrition during pregnancy and lactation affected the
      development of AD in offspring, using a transgenic AD mouse model. Female triple
      transgenic AD dam mice (3xTgAD) were exposed to a high-fat (60% energy from fat)
      or control diet during pregnancy and lactation. After weaning (at 3 weeks of
      age), female offspring were placed on a control diet and monitored up until 12
      months of age during which time behavioural tests were performed. A transient
      increase in body weight was observed in 4-week-old offspring 3xTgAD mice from
      dams fed a high-fat diet. However, by 5 weeks of age the body weight of 3xTgAD
      mice from the maternal high-fat fed group was no different when compared to
      control-fed mice. A maternal high-fat diet led to a significant impairment in
      memory in 2- and 12-month-old 3xTgAD offspring mice when compared to offspring
      from control fed dams. These effects of a maternal high-fat diet on memory were
      accompanied by a significant increase (50%) in the number of tau positive
      neurones in the hippocampus. These data demonstrate that a high-fat diet during
      pregnancy and lactation increases memory impairments in female 3xTgAD mice and
      suggest that early life events during development might influence the onset and
      progression of AD later in life. 

PMID- 24918776
TI  - Cervical pessary use and preterm birth.
AB  - Preterm birth remains a considerable public health concern and priority. Little
      headway has been made in the prevention of preterm birth despite considerable
      research in this area. New ideas and treatments are desperately needed. The
      pessary has emerged as a possible treatment for the prevention of preterm birth
      in both singleton and twin gestations. It appears to be low cost with minimal
      side effects. This review focuses on the available evidence for the use of
      cervical pessaries for the prevention of preterm birth, especially in a high-risk
      population with a shortened cervical length. Larger scale randomized-controlled
      trials are warranted before incorporation of the pessary into standard
      obstetrical practice. 

PMID- 24918777
TI  - A novel method to reduce time investment when processing videos from camera trap
      studies.
AB  - Camera traps have proven very useful in ecological, conservation and behavioral
      research. Camera traps non-invasively record presence and behavior of animals in
      their natural environment. Since the introduction of digital cameras, large
      amounts of data can be stored. Unfortunately, processing protocols did not evolve
      as fast as the technical capabilities of the cameras. We used camera traps to
      record videos of Eurasian beavers (Castor fiber). However, a large number of
      recordings did not contain the target species, but instead empty recordings or
      other species (together non-target recordings), making the removal of these
      recordings unacceptably time consuming. In this paper we propose a method to
      partially eliminate non-target recordings without having to watch the recordings,
      in order to reduce workload. Discrimination between recordings of target species
      and non-target recordings was based on detecting variation (changes in pixel
      values from frame to frame) in the recordings. Because of the size of the target
      species, we supposed that recordings with the target species contain on average
      much more movements than non-target recordings. Two different filter methods were
      tested and compared. We show that a partial discrimination can be made between
      target and non-target recordings based on variation in pixel values and that
      environmental conditions and filter methods influence the amount of non-target
      recordings that can be identified and discarded. By allowing a loss of 5% to 20%
      of recordings containing the target species, in ideal circumstances, 53% to 76%
      of non-target recordings can be identified and discarded. We conclude that adding
      an extra processing step in the camera trap protocol can result in large time
      savings. Since we are convinced that the use of camera traps will become
      increasingly important in the future, this filter method can benefit many
      researchers, using it in different contexts across the globe, on both videos and
      photographs. 

PMID- 24918778
TI  - The real-time dynamic monitoring of microRNA function in cholangiocarcinoma.
AB  - BACKGROUND: Although many studies have confirmed a relationship between microRNAs
      (miRNAs) and cholangiocarcinoma (CCA), the real-time dynamics of miRNA function
      have not been examined. METHODS: miRNA reporter constructs were generated using a
      recombinant adeno-associated virus vector, which contained complementary
      sequences for six miRNAs (miR-200a, miR-200b, miR-21, miR-146a, miR-155, and miR
      221), along with two independent expression cassettes encoding the fluorescent
      reporter genes Fluc and Gluc. The spatio-temporal function of each miRNA was
      monitored both in CCA and control tissues. RESULTS: All miRNAs participated in
      CCA development, with distinct patterns of expression over time. The activity of
      miR-21 was significantly lower in female T3N0M0 CCA tissue relative to controls
      at three time points, yet was higher in two male T3N1M0 CCA tissues. The
      difference in miR-200b function between two male T3N1M0 CCA tissues and their
      corresponding controls peaked at 24 h, while function in a female T3N0M0 CCA was
      detected only at 72 h. The four remaining miRNAs (miR-200a, miR146a, miR-155, and
      miR-221) displayed patient-specific activity patterns in both CCA and control
      tissues. CONCLUSION: Significant variability was observed in the temporal
      function of all six miRNAs, which may play an important role in the development
      of CCA.

PMID- 24918779
TI  - Assessing landscape constraints on species abundance: does the neighborhood limit
      species response to local habitat conservation programs?
AB  - Landscapes in agricultural systems continue to undergo significant change, and
      the loss of biodiversity is an ever-increasing threat. Although habitat
      restoration is beneficial, management actions do not always result in the desired
      outcome. Managers must understand why management actions fail; yet, past studies
      have focused on assessing habitat attributes at a single spatial scale, and often
      fail to consider the importance of ecological mechanisms that act across spatial
      scales. We located survey sites across southern Nebraska, USA and conducted point
      counts to estimate Ring-necked Pheasant abundance, an economically important
      species to the region, while simultaneously quantifying landscape effects using a
      geographic information system. To identify suitable areas for allocating limited
      management resources, we assessed land cover relationships to our counts using a
      Bayesian binomial-Poisson hierarchical model to construct predictive Species
      Distribution Models of relative abundance. Our results indicated that landscape
      scale land cover variables severely constrained or, alternatively, facilitated
      the positive effects of local land management for Ring-necked Pheasants. 

PMID- 24918780
TI  - Chemically optimizing operational efficiency of molecular rotary motors.
AB  - Unidirectional molecular rotary motors that harness photoinduced cis-trans (E-Z)
      isomerization are promising tools for the conversion of light energy to
      mechanical motion in nanoscale molecular machines. Considerable progress has been
      made in optimizing the frequency of ground-state rotation, but less attention has
      been focused on excited-state processes. Here the excited-state dynamics of a
      molecular motor with electron donor and acceptor substituents located to modify
      the excited-state reaction coordinate, without altering its stereochemistry, are
      studied. The substituents are shown to modify the photochemical yield of the
      isomerization without altering the motor frequency. By combining 50 fs resolution
      time-resolved fluorescence with ultrafast transient absorption spectroscopy the
      underlying excited-state dynamics are characterized. The Franck-Condon excited
      state relaxes in a few hundred femtoseconds to populate a lower energy dark state
      by a pathway that utilizes a volume conserving structural change. This is
      assigned to pyramidalization at a carbon atom of the isomerizing bridging double
      bond. The structure and energy of the dark state thus reached are a function of
      the substituent, with electron-withdrawing groups yielding a lower energy longer
      lived dark state. The dark state is coupled to the Franck-Condon state and decays
      on a picosecond time scale via a coordinate that is sensitive to solvent
      friction, such as rotation about the bridging bond. Neither subpicosecond nor
      picosecond dynamics are sensitive to solvent polarity, suggesting that
      intramolecular charge transfer and solvation are not key driving forces for the
      rate of the reaction. Instead steric factors and medium friction determine the
      reaction pathway, with the sterically remote substitution primarily influencing
      the energetics. Thus, these data indicate a chemical method of optimizing the
      efficiency of operation of these molecular motors without modifying their overall
      rotational frequency. 

PMID- 24918782
TI  - Higher bone turnover is related to spinal radiographic damage and low bone
      mineral density in ankylosing spondylitis patients with active disease: a cross
      sectional analysis.
AB  - INTRODUCTION: Ankylosing spondylitis (AS) is characterized by excessive bone
      formation and bone loss. Our aim was to investigate the association of bone
      turnover markers (BTM) with spinal radiographic damage and bone mineral density
      (BMD) in AS patients with active disease. METHODS: 201 consecutive AS outpatients
      of the Groningen Leeuwarden AS (GLAS) cohort were included. Serum markers of bone
      resorption (C-telopeptides of type-I collagen, sCTX) and bone formation
      (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase,
      BALP) were measured. Z-scores were used to correct for the normal influence that
      age and gender have on bone turnover. Radiographs were scored by two independent
      readers according to modified Stoke AS Spinal Score (mSASSS). The presence of
      complete bridging (ankylosis of at least two vertebrae) was considered as measure
      of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or
      hip BMD Z-score <= -1. RESULTS: Of the 151 patients with complete data, 52 (34%)
      had >= 1 complete bridge, 49 (33%) had >= 1 syndesmophyte (non-bridging), and 50
      (33%) had no syndesmophytes. 66 (44%) had low BMD. Patients with bridging had
      significantly higher sCTX and PINP Z-scores than patients without bridging (0.43
      vs. -0.55 and 0.55 vs. 0.04, respectively). Patients with low BMD had
      significantly higher sCTX Z-score than patients with normal BMD (-0.08 vs. 
      0.61). After correcting for gender, symptom duration, and CRP, sCTX Z-score
      remained significantly related to the presence of low BMD alone (OR: 1.60),
      bridging alone (OR: 1.82), and bridging in combination with low BMD (OR: 2.26).
      CONCLUSIONS: This cross-sectional study in AS patients with active and relatively
      long-standing disease demonstrated that higher serum levels of sCTX, and to a
      lesser extent PINP, are associated with the presence of complete bridging. sCTX
      was also associated with low BMD. Longitudinal studies are needed to confirm that
      serum levels of sCTX can serve as objective marker for bone-related outcome in
      AS.

PMID- 24918784
TI  - Single-incision laparoscopic ileocecectomy in children with Crohn's disease.
AB  - INTRODUCTION: We previously reported our experience with standard laparoscopic
      ileocecectomy, but we have recently used a single-incision laparoscopic approach.
      PATIENTS AND METHODS: We conducted a retrospective review of a single surgeon's
      experience from 2009 to 2013. RESULTS: Twenty-eight children 11-18 years of age
      (mean, 15.5 years) with a mean body mass index of 18.9+/-3 kg/m(2) underwent
      single-incision laparoscopic ileocecectomy for Crohn's disease. Mean operative
      time was 86.5+/-25.9 minutes (range, 56-166 minutes). There were no extra ports
      placed or conversions to open surgery. Five children (18%) were on parenteral
      nutrition at time of surgery, 14 (50%) were on steroids, and 9 (32%) were on
      tumor necrotic factor inhibitors. A stapled extracorporeal anastomosis was
      performed in all children. Complications included abscess (n=4), small bowel
      obstruction (n=3), superficial wound infection (n=3), and small bowel perforation
      (n=1). Some patients had more than one complication. Of those with complications,
      5 (56%) were on steroids, 5 (56%) were on tumor necrotic factor inhibitors, and 1
      patient was on both. The perforation occurred at a point of adhesiolysis also
      involved with Crohn's disease. There were no anastomotic leaks. Median follow-up
      was 17 months (range, 1-47 months). CONCLUSIONS: Single-incision laparoscopic
      ileocecectomy is safe and feasible in pediatric patients with Crohn's disease.

PMID- 24918783
TI  - A Pseudomonas aeruginosa EF-hand protein, EfhP (PA4107), modulates stress
      responses and virulence at high calcium concentration.
AB  - Pseudomonas aeruginosa is a facultative human pathogen, and a major cause of
      nosocomial infections and severe chronic infections in endocarditis and in cystic
      fibrosis (CF) patients. Calcium (Ca2+) accumulates in pulmonary fluids of CF
      patients, and plays a role in the hyperinflammatory response to bacterial
      infection. Earlier we showed that P. aeruginosa responds to increased Ca2+
      levels, primarily through the increased production of secreted virulence factors.
      Here we describe the role of putative Ca2+-binding protein, with an EF-hand
      domain, PA4107 (EfhP), in this response. Deletion mutations of efhP were
      generated in P. aeruginosa strain PAO1 and CF pulmonary isolate, strain FRD1. The
      lack of EfhP abolished the ability of P. aeruginosa PAO1 to maintain
      intracellular Ca2+ homeostasis. Quantitative high-resolution 2D-PAGE showed that
      the efhP deletion also affected the proteomes of both strains during growth with
      added Ca2+. The greatest proteome effects occurred when the pulmonary isolate was
      cultured in biofilms. Among the proteins that were significantly less abundant or
      absent in the mutant strains were proteins involved in iron acquisition,
      biosynthesis of pyocyanin, proteases, and stress response proteins. In support,
      the phenotypic responses of FRD1 DeltaefhP showed that the mutant strain lost its
      ability to produce pyocyanin, developed less biofilm, and had decreased
      resistance to oxidative stress (H2O2) when cultured at high [Ca2+]. Furthermore,
      the mutant strain was unable to produce alginate when grown at high [Ca2+] and no
      iron. The effect of the DeltaefhP mutations on virulence was determined in a
      lettuce model of infection. Growth of wild-type P. aeruginosa strains at high
      [Ca2+] causes an increased area of disease. In contrast, the lack of efhP
      prevented this Ca2+-induced increase in the diseased zone. The results indicate
      that EfhP is important for Ca2+ homeostasis and virulence of P. aeruginosa when
      it encounters host environments with high [Ca2+].

PMID- 24918785
TI  - Small-area estimation of the probability of toxocariasis in New York City based
      on sociodemographic neighborhood composition.
AB  - Toxocariasis is increasingly recognized as an important neglected infection of
      poverty (NIP) in developed countries, and may constitute the most important NIP
      in the United States (US) given its association with chronic sequelae such as
      asthma and poor cognitive development. Its potential public health burden
      notwithstanding, toxocariasis surveillance is minimal throughout the US and so
      the true burden of disease remains uncertain in many areas. The Third National
      Health and Nutrition Examination Survey conducted a representative serologic
      survey of toxocariasis to estimate the prevalence of infection in diverse US
      subpopulations across different regions of the country. Using the NHANES III
      surveillance data, the current study applied the predicted probabilities of
      toxocariasis to the sociodemographic composition of New York census tracts to
      estimate the local probability of infection across the city. The predicted
      probability of toxocariasis ranged from 6% among US-born Latino women with a
      university education to 57% among immigrant men with less than a high school
      education. The predicted probability of toxocariasis exhibited marked spatial
      variation across the city, with particularly high infection probabilities in
      large sections of Queens, and smaller, more concentrated areas of Brooklyn and
      northern Manhattan. This investigation is the first attempt at small-area
      estimation of the probability surface of toxocariasis in a major US city. While
      this study does not define toxocariasis risk directly, it does provide a much
      needed tool to aid the development of toxocariasis surveillance in New York City.

PMID- 24918786
TI  - Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and
      muscle mitochondria.
AB  - HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway and the
      target of cholesterol-lowering statins. We characterized the C. elegans hmgr
      1(tm4368) mutant, which lacks HMG-CoA reductase, and show that its phenotypes
      recapitulate that of statin treatment, though in a more severe form.
      Specifically, the hmgr-1(tm4368) mutant has defects in growth, reproduction and
      protein prenylation, is rescued by exogenous mevalonate, exhibits constitutive
      activation of the UPRer and requires less mevalonate to be healthy when the UPRmt
      is activated by a constitutively active form of ATFS-1. We also show that
      different amounts of mevalonate are required for different physiological
      processes, with reproduction requiring the highest levels. Finally, we provide
      evidence that the mevalonate pathway is required for the activation of the UPRmt.

PMID- 24918787
TI  - Determinants within the C-terminal domain of Streptomyces lividans acetyl-CoA
      synthetase that block acetylation of its active site lysine in vitro by the
      protein acetyltransferase (Pat) enzyme.
AB  - Reversible lysine acetylation (RLA) is a widespread regulatory mechanism that
      modulates the function of proteins involved in diverse cellular processes. A
      strong case has been made for RLA control exerted by homologues of the Salmonella
      enterica protein acetyltransferase (SePat) enzyme on the broadly distributed AMP
      forming CoA ligase (a.k.a. acyl-CoA synthetases) family of metabolic enzymes,
      with acetyl-CoA synthetase (Acs) being the paradigm in the field. Here we
      investigate why the Acs homologue in Streptomyces lividans (SlAcs) is poorly
      acetylated in vitro by the S. lividans protein acetyltransferase (SlPat) enzyme.
      Chimeras of S. enterica Acs (SeAcs) and S. lividans Acs (SlAcs) constructed
      during the course of this work were acetylated by SlPatA in vitro, retained most
      of their activity, and were under RLA control in a heterologous host. We
      identified SeAcs residues N- and C-terminal to the target lysine that when
      introduced into SlAcs, rendered the latter under RLA control. These results lend
      further support to the idea that Pat enzymes interact with extensive surfaces of
      their substrates. Finally, we suggest that acetylation of SlAcs depends on
      factors or conditions other than those present in our in vitro system. We also
      discuss possible explanations why SlAcs is not controlled by RLA as defined in
      other bacterial species. 

PMID- 24918788
TI  - The impact of weight loss on weight-related quality of life and health
      satisfaction: results from a trial comparing canagliflozin with sitagliptin in
      triple therapy among people with type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is primarily a self-managed disease in which self
      care behaviors play an important role in achieving optimal outcomes. Because self
      care does not result in immediate tangible or noticeable benefits, adherence to
      such a regimen can be confusing, difficult, and frustrating. People are more
      likely to adhere to treatment regimens that offer benefits from the patient
      perspective, such as convenience, avoidance of hypoglycemic episodes, and weight
      loss, compared with regimens that do not. In this study, we explored the impact
      of the average weight loss amount demonstrated with canagliflozin treatment on
      improvement in 3 patient-relevant outcomes that have been linked to performance
      of healthy behaviors and better outcomes in T2DM: weight-related quality of life,
      as measured by the Impact of Weight on Quality of Life-Lite (IWQOL-Lite)
      questionnaire, and satisfaction with physical health and emotional health, as
      measured by the Current Health Satisfaction Questionnaire (CHES-Q), using data
      from a previously reported study. Weight loss of an amount demonstrated in
      clinical trials of canagliflozin was associated with improvements in weight
      related quality of life and satisfaction with physical and emotional health,
      concepts shown to be important to the persistent and consistent performance of
      healthy behaviors. 

PMID- 24918789
TI  - Safety and tolerability of canagliflozin in patients with type 2 diabetes
      mellitus: pooled analysis of phase 3 study results.
AB  - BACKGROUND: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed
      for treating type 2 diabetes mellitus (T2DM). METHODS: The safety/tolerability
      profile of canagliflozin 100 and 300 mg over 26 weeks was assessed using an
      integrated analysis of data pooled from 4 placebo-controlled, phase 3 studies
      representing a broad range of patients with T2DM (N = 2313; mean age, 56.0 years;
      glycated hemoglobin [HbA1c], 8.0%; body mass index, 32.1 kg/m2; estimated
      glomerular filtration rate, 88.1 mL/min/1.73 m2) on various prespecified
      background diabetes mellitus treatments. Safety/tolerability evaluations included
      adverse event (AE) reporting, with additional data collection prespecified for
      selected AEs, and assessments of renal-related, lipid, and other safety
      laboratory parameters. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01081834;
      NCT01106625; NCT01106677; NCT01106690. RESULTS: The overall incidence of AEs was
      similar with canagliflozin 100 and 300 mg and placebo; incidences of serious AEs
      and AEs leading to study discontinuation were low across groups. Canagliflozin
      was associated with higher incidences than placebo of genital mycotic infections
      and osmotic diuresis-related AEs; these were generally considered by the
      investigator to be mild to moderate in intensity and infrequently led to
      discontinuation. Canagliflozin was associated with transient reductions in
      estimated glomerular filtration rate that trended toward baseline over the
      assessment period; incidences of renal-related AEs were low across groups. Dose
      related increases in the incidence of hypoglycemia episodes were seen with
      canagliflozin versus placebo in patients on background sulfonylurea; incidences
      of severe hypoglycemia were low across groups. Hypoglycemia incidence was low
      overall in patients not on background sulfonylurea, but slightly higher with
      canagliflozin versus placebo. Relative to placebo, favorable changes in high
      density lipoprotein cholesterol and triglycerides were seen with canagliflozin;
      increases in low-density lipoprotein cholesterol were also seen. Canagliflozin
      was associated with small changes in other safety laboratory parameters that were
      not clinically meaningful. CONCLUSIONS: Canagliflozin as monotherapy and as
      combination therapy was generally well tolerated in patients with T2DM
      inadequately controlled on their current diabetes mellitus treatment.

PMID- 24918790
TI  - Effect of renal impairment on the pharmacokinetics, efficacy, and safety of
      albiglutide.
AB  - BACKGROUND: Chronic kidney disease is frequently present in patients with type 2
      diabetes mellitus (T2DM). New therapeutic options in this patient subpopulation
      are needed. OBJECTIVES: Assess the effect of renal impairment on the
      pharmacokinetics (PK), efficacy, and safety of albiglutide in single- and
      multiple-dose studies. METHODS: Pharmacokinetics, safety, and efficacy of once
      weekly albiglutide in patients with T2DM was assessed from a single-dose (30 mg),
      nonrandomized, open-label study (N = 41) including subjects with normal and
      varying degrees of renal impairment, including hemodialysis, and a pooled
      analysis of 4 phase 3, randomized, double-blind (1 open-label), active or placebo
      controlled multiple-dose studies. The pooled analysis of the latter 4 studies (N
      = 1113) was part of the population PK analysis, which included subjects with
      normal and varying degrees of renal impairment (mild, moderate, severe) treated
      with albiglutide (30 to 50 mg) to primary end points of 26 to 52 weeks. RESULTS:
      Single-dose PK showed area-under-the-curve ratios (and 90% CIs) of 1.32 (0.96
      1.80), 1.39 (1.03-1.89), and 0.99 (0.63-1.57) for the moderate, severe, and
      hemodialysis groups, respectively, relative to the normal group. Results indicate
      that modest increases in plasma concentration of albiglutide were observed with
      the severity of renal impairment. There was a trend for more glycemic lowering as
      the estimated glomerular filtration rate decreased. The severe group had a higher
      frequency of gastrointestinal (eg, diarrhea, constipation, nausea, and vomiting)
      and hypoglycemic (with background sulfonylurea use) events compared with patients
      with mild or moderate renal impairment. CONCLUSION: The PK, efficacy, and safety
      data indicate that albiglutide has a favorable benefit/risk ratio in patients
      with T2DM and varying degrees of renal impairment, and the need for a dose
      adjustment is not suggested. Experience in patients with more severe renal
      impairment is very limited, so the recommendation is to use albiglutide carefully
      in this population. CLINICAL TRIAL REGISTRATION:
      (ClinicalTrials.gov):NCT00938158, NCT00849017, NCT00838916, NCT00839527,
      NCT0198539.

PMID- 24918791
TI  - Management of patients using combination therapy with pioglitazone and a
      dipeptidyl peptidase-4 inhibitor: an analysis of initial versus sequential
      combination therapy.
AB  - Current type 2 diabetes mellitus (T2DM) treatment involves progressive
      interventions from lifestyle changes to pharmacological therapies. Previous
      studies found that combination therapy with a dipeptidyl peptidase-4 inhibitor
      (DPP-4i) and pioglitazone (PIO) is more effective than monotherapies in treating
      poorly controlled T2DM, but there is no consensus on whether these drugs should
      be initiated at the same time (initial combination therapy) or sequentially. We
      aimed to assess glycemic control with initial versus sequential combination
      therapy with PIO and a DPP-4i in patients with glycosylated hemoglobin (HbA1c)
      levels >= 7%. A retrospective chart review was conducted on T2DM patients from
      diverse geographic sites in the United States initiating therapies from March 2,
      2010 to February 28, 2011. Patients were selected for initial combination
      therapy, if starting PIO and a DPP-4i within 30 days of each other, or sequential
      combination therapy, if first taking PIO alone for >= 60 days before adding a DPP
      4i within 1 year of PIO initiation. The HbA1c level reduction from baseline was
      compared between cohorts using linear regression models adjusting for
      demographics, baseline HbA1c, T2DM duration, comorbidities, and various
      medications. There were 250 patients in the initial and 211 in the sequential
      combination therapy cohorts; 57.3% were male, 65.3% were Caucasian, and the mean
      age was 54.3 years. Patients receiving initial combination therapy had a
      significantly higher mean baseline HbA1c level (8.6% vs 8.0%, P < 0.0001), a
      higher prevalence of coronary artery disease (11.6% vs 6.2%, P = 0.0430), and a
      lower prevalence of hyperlipidemia (56.4% vs 67.8%, P = 0.0120) and of
      hypertension (62.4% vs 72.0%, P = 0.0290), compared with the sequential therapy
      cohort. In adjusted analyses, initial combination therapy was associated with a
      significantly greater reduction in HbA1c levels than sequential combination
      therapy at months 12, 16, and 20 (-0.977 vs -0.819, P = 0.034; -1.453 vs -1.242,
      P = 0.048; and -1.182 vs -0.810, P = 0.013, respectively). Our findings suggest
      initial combination therapy may be the preferred option in choosing combination
      therapies.

PMID- 24918792
TI  - Potential impact of dipeptidyl peptidase-4 inhibitors on cardiovascular
      pathophysiology in type 2 diabetes mellitus.
AB  - Cardiovascular (CV) disease remains the major cause of mortality and morbidity in
      patients with type 2 diabetes mellitus (T2DM). The pathogenesis of CV disease in
      T2DM is complex and multifactorial, and includes abnormalities in endothelial
      cells, vascular smooth muscle cells, myocardium, platelets, and the coagulation
      cascade. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of agents
      that act by potentiating the action of glucagon-like peptide-1 (GLP-1) and
      glucose-dependent insulinotropic polypeptide. This review summarizes CV disease
      pathophysiology in T2DM and the potential effect of DPP-4 inhibitors on CV risk
      in patients with T2DM. Preclinical and small observational studies and post hoc
      analyses of clinical trial data suggest that DPP-4 inhibitors may have beneficial
      CV effects. Some effects of DPP-4 inhibitors are GLP-1 dependent, whereas others
      may be due to GLP-1-independent actions of DPP-4 inhibitors. Analyses of major
      adverse CV events occurring during clinical development of DPP-4 inhibitors found
      no increased risk of CV events or mortality and even a potential reduction in CV
      events. Two large CV outcome trials have been completed and report that
      saxagliptin and alogliptin did not increase or decrease adverse CV outcomes in
      patients with T2DM and CV disease or at high risk for adverse CV events. More
      patients in the saxagliptin group than in the placebo group were hospitalized for
      heart failure, and there was a similar numerically increased risk of
      hospitalization for heart failure with alogliptin; however, the risk was not
      significantly greater compared with placebo. Dipeptidyl peptidase-4 inhibitors
      may affect some of the pathologic processes involved in the increased CV risk
      inherent in T2DM. 

PMID- 24918793
TI  - Evidence-based practice use of incretin-based therapy in the natural history of
      diabetes.
AB  - The incretin class of anti-hyperglycemic agents, including glucagon-like peptide
      1 receptor agonists and dipeptidyl peptidase-inhibitors, is an important addition
      to the therapeutic armamentarium for the management of appropriate patients with
      type 2 diabetes mellitus as an adjunct to diet and exercise and/or with the
      agents metformin, sulfonylureas, thiazolidinediones, or any combination thereof.
      More recently, US Food and Drug Administration (FDA)-approved indications for
      incretins were expanded to include use with basal insulin. This review article
      takes an evidence-based practice approach in discussing the importance of
      aggressive treatment for diabetes, the principles of incretin physiology and
      pathophysiology, use of glucagon-like peptide-1 receptor agonists and dipeptidyl
      peptidase-4 inhibitors, and patient types and contexts where incretin therapy has
      been found beneficial, from metabolic syndrome to overt diabetes. 

PMID- 24918794
TI  - Combining clinical judgment with guidelines for the management of type 2
      diabetes: overall standards of comprehensive care.
AB  - The rising toll of type 2 diabetes mellitus (T2DM) on patients and society has
      resulted in a wide variety of guidelines and therapies to address the need to
      combat this trend. Given the heterogeneity of T2DM and the different responses
      patients have to therapies, as well as the continued need for patients to
      institute lifestyle changes, guidelines published by the American Diabetes
      Association/European Association for the Study of Diabetes and the American
      Association of Clinical Endocrinologists/American College of Endocrinology have
      in recent years increased the focus on personalized and patient-centered care.
      How to best assimilate the overall standards of care for T2DM into clinical
      practice remains a challenge. The 4 pillars of effective diabetes management are
      a unifying framework and approach to clinical practice that can be integrated
      with the latest diabetes guidelines. These 4 pillars are lifestyle modifications
      involving (1) diet, (2) exercise, (3) a system to monitor preprandial and
      postprandial blood glucose and glycated hemoglobin levels, and (4) pharmacologic
      intervention when required. This article reviews the overall standards of care
      for T2DM, focusing on the first 3 nonpharmacologic pillars, and provides
      suggestions for integrating this approach with the current American Diabetes
      Association and American Association of Clinical Endocrinologists/American
      College of Endocrinology guidelines. Barriers to effective implementation of
      exercise programs, diets, and monitoring of blood glucose levels are discussed
      along with clinical strategies to overcome these barriers and achieve effective
      glycemic control and lifestyle changes for patients with T2DM. Personalized
      approaches to the management of T2DM are also reviewed. 

PMID- 24918795
TI  - Application of clinical judgment and guidelines to achieving glycemic goals in
      type 2 diabetes: focus on pharmacologic therapy.
AB  - Successful management of patients with type 2 diabetes mellitus requires
      attention to 4 pillars of care: diet, exercise, blood glucose monitoring, and
      pharmacologic therapy. For pharmacologic therapy, the availability of multiple
      drugs in different classes can make choices regarding initiation and
      intensification of treatment challenging. This article, focusing on clinical
      practice, reviews and provides guidance on assessing recommendations made by the
      latest diabetes guidelines for pharmacotherapy published by the American Diabetes
      Association and the American Academy of Clinical Endocrinologists. The article
      discusses how diabetes guidelines evolved, their move toward personalization of
      therapy, and their effective use in clinical practice. An appraisal of various
      pharmacologic strategies is integrated with the author's approach to achieving
      glycemic goals with a minimum of weight gain or hypoglycemic episodes. Using
      patients' baseline glycated hemoglobin levels and the degree to which their
      fasting and postprandial plasma levels contribute to their hyperglycemia is
      explained as a strategy by which drugs can be chosen that act on these
      parameters. Lifestyle interventions such as diet and exercise should continue to
      form the foundation of the therapeutic alliance between the clinician and patient
      as pharmacologic therapy is initiated or intensified. 

PMID- 24918796
TI  - Biosimilar insulins are coming: the top 10 things you should know.
AB  - Biologic drugs, such as currently prescribed insulins, are large, complex, 3
      dimensional molecules manufactured in biological systems. The complexity of the
      structure of the biologic drug and its manufacturing process means that it is
      challenging to create a biologic drug that is identical to the original branded
      drug. With the potential availability on the horizon of follow-on insulin
      products (also known as biosimilar insulins) in the United States and other
      countries where they are not currently in use, physicians (and other prescribers)
      need to be aware of the potential benefits and concerns regarding biosimilar
      insulins in order to facilitate informed decision making and to provide the best
      possible advice and guidance to their patients with diabetes. This article offers
      a brief, practical overview regarding biosimilar insulins by answering 10 key
      questions about the topic. 

PMID- 24918797
TI  - Influence of baseline glycemia on outcomes with insulin glargine use in patients
      uncontrolled on oral agents.
AB  - PURPOSE: Optimizing glycemic control in patients with type 2 diabetes mellitus
      (T2DM) not controlled with >= 1 oral antidiabetes drugs (OADs) is challenging.
      Many therapeutic options exist; however, data comparing the effectiveness of
      different strategies are lacking for the management of patients with T2DM. Our
      study aim was to provide comparative data on efficacy and hypoglycemia when
      initiating insulin glargine (glargine) versus alternative treatment options (not
      including the newest antidiabetes agents, glucagon-like peptide [GLP]-1 receptor
      agonists, dipeptidyl peptidase [DPP]-4 inhibitors or sodium-glucose linked
      transporter [SGLT]-2 inhibitors) in insulin-naive patients with T2DM who remained
      uncontrolled with OADs. METHODS: Patient-level data were pooled from 9 randomized
      controlled trials of >= 24 weeks duration with comparable patient populations.
      The effect of adding glargine was compared with intensification of lifestyle
      interventions or OADs, addition of neutral protamine Hagedorn (NPH) insulin,
      insulin lispro, premixed insulin, or all comparators pooled, on patient glycated
      hemoglobin (HbA1c) level, fasting plasma glucose level, weight, and hypoglycemia.
      RESULTS: A greater proportion of patients achieved a target HbA1c level <= 7.0%
      with glargine treatment than with pooled comparators, intensification of OADs, or
      lifestyle interventions; there was no difference when compared with NPH,
      premixed, or insulin lispro use. The rate for reported hypoglycemic events was
      lower for glargine use than for pooled comparators or other insulins, but higher
      compared with intensification of lifestyle interventions or OADs. When stratified
      by baseline HbA1c level, efficacy/target attainment with glargine use was better
      than for pooled comparators across all HbA1c strata; OAD intensification, when
      baseline HbA1c level was >= 8.0%; and premixed insulin if baseline HbA1c level
      was < 8.0%; but similar to other insulins for all other categories. The incidence
      of reported hypoglycemia was less frequent with glargine use than other insulins,
      but more frequent than intensification of lifestyle interventions or OADs.
      CONCLUSION: When adequate glycemic control is not achieved using OADs in patients
      with T2DM, initiating insulin glargine is generally less likely to elicit
      hypoglycemia than initiating NPH, premixed, or prandial insulins, and the benefit
      risk balance supports initiating insulin rather than intensification of OAD
      therapy when baseline HbA1c level is >= 8.0%.

PMID- 24918798
TI  - Expanded colesevelam administration options with oral suspension formulation for
      patients with diabetes and hypercholesterolemia.
AB  - INTRODUCTION: Colesevelam HCl (colesevelam) is a bile acid sequestrant initially
      approved by the US Food and Drug Administration (FDA) in 2000 as an adjunct to
      diet and exercise to lower elevated low-density lipoprotein cholesterol (LDL-C)
      levels in adults with primary lipidemia, as monotherapy, or in combination with a
      statin. More recently, the drug was approved for use in adults with type 2
      diabetes mellitus (T2DM) to improve glycemic control. Thus, colesevelam is
      currently the only single-agent monotherapy approved by the FDA to lower both LDL
      C and glycated hemoglobin (A1c) levels in adults with T2DM and elevated LDL-C.
      Moreover, the formulation options for colesevelam have also expanded since its
      original approval. MATERIALS AND METHODS: A Medline search was conducted to
      provide evidence to support the efficacy and safety for the use of colesevelam
      tablets or oral suspension preparations when treating patients with lipidemia,
      T2DM, or both. No limitations were placed on publication date or any other
      parameter. RESULTS: Clinical studies have shown that colesevelam is efficacious
      in lowering LDL-C levels, improving the lipid profile, and improving glycemic
      control by reducing both A1c and fasting plasma glucose levels in T2DM.
      Equilibrium and kinetics data show that colesevelam is equivalent in its tablet
      and oral suspension formulation. CONCLUSION: Having 2 effective oral routes
      enhances convenience and improves compliance, both of which contribute to maximal
      therapeutic outcomes. These compliance benefits are due to the ease and
      flexibility of preparing the powder in various beverages and the pleasant taste
      from the inclusion of a low-calorie citrus flavoring.

PMID- 24918799
TI  - A short-acting GLP-1 analog or prandial insulin to supplement basal insulin?-
      Moving toward personalized management of type 2 diabetes mellitus.
AB  - New models of health care delivery that emphasize patient-centered care affirm
      the need for alternatives to add-on prandial insulin therapy when optimized basal
      insulin fails to maintain glycemic control in patients with type 2 diabetes
      mellitus. Regimens that are easy to teach, convenient, and flexible generally
      improve the outlook for long-term success. Our review reconsiders traditional
      barriers to insulin intensification in primary care and provides an illustration
      of how the benefits and drawbacks of > 1 choice of action--specifically, adding
      rapid-acting insulin or a short-acting glucagon-like peptide-1 analog--can be
      weighed by the patient and provider together to determine the best next treatment
      step that balances efficacy, safety, and adherence to therapy. Technological,
      organizational, and interpersonal strategies for applying personalized management
      at this often challenging crossroads of diabetes management are also described.

PMID- 24918800
TI  - Health care provider management of patients with type 2 diabetes mellitus:
      analysis of trends in attitudes and practices.
AB  - OBJECTIVE: To identify attitudes and practices of endocrinologists (ENDOs),
      family practitioners (FPs), internists (IMs), primary care nurse practitioners
      (NPs), physician assistants (PAs), certified diabetes educators (CDEs), retail
      pharmacists (R-PHs), and hospital pharmacists (H-PHs) with respect to type 2
      diabetes mellitus (T2DM) management; to compare current study data with results
      from a similar 2011 study. METHODS: A nominal group technique focus group
      identified barriers to optimal management of patients with T2DM. Five case
      vignette surveys were created, 1 for each group of health care professionals
      (HCPs): ENDOs; FPs and IMs; NPs and PAs; CDEs; and R-PHs and H-PHs. Surveys were
      tailored to each group. Versions were as similar as possible to each other and to
      the 2011 surveys to facilitate comparisons. Questions assessed guideline
      familiarity; knowledge of insulin formulations, glucagon-like peptide-1 (GLP-1)
      receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors; patterns of
      referral to ENDOs and CDEs; as well as cultural barriers and communication
      barriers. Surveys were distributed by e-mail/fax to a nationally representative,
      random sample of US HCPs during January and February 2013. RESULTS AND
      CONCLUSIONS: Notable shifts from 2011 included NPs' increased familiarity with
      American Diabetes Association (ADA) guidelines; FPs, IMs, NPs, and PAs continued
      comfort with prescribing long-acting basal insulin but less with basal-bolus,
      Neutral Protamine Hagedorn insulin alone, or human premixed insulin; increased
      pharmacists' comfort in discussing long-acting basal insulin; increased
      likelihood that FPs will refer patients with recurrent hypoglycemia unable to
      achieve target glycated hemoglobin level to an ENDO; and continued incorporation
      of insulin and incretins into treatment regimens. The trends suggest gaps in
      perception, knowledge, and management practices to be addressed by education.
      Most HCPs lack confidence in using insulin regimens more complex than long-acting
      insulin alone. All providers need education on T2DM management guidelines,
      differences between GLP-1 agonists and DPP-4 inhibitors, and how to intensify
      therapy for patients not reaching goal blood glycemic level with use of multiple
      agents. Pharmacists might benefit from education on glycemic treatment goals.

PMID- 24918801
TI  - Anti-diabetes therapy: safety considerations for patients with impaired kidney
      function.
AB  - The presence of type 2 diabetes mellitus (T2DM) is a common risk factor for the
      development of chronic kidney disease, but appropriate glycemic control can slow
      the progression of kidney dysfunction in patients with T2DM. The kidney plays a
      role in insulin resistance and gluconeogenesis, therefore, impaired kidney
      function alters glucose dynamics compared with normal kidney function, thus
      affecting antihyperglycemic treatment strategies. Glycemic management is further
      complicated by reduced drug clearance and a greater risk of hypoglycemia with use
      of certain medications, notably the sulfonylureas. Of the classes of
      antihyperglycemic drugs discussed in this review, caution is advised when using
      some classes in patients with T2DM and kidney disease. 

PMID- 24918802
TI  - Efficacy and risk of hypoglycemia with use of insulin glargine or comparators in
      patients with cardiovascular risk factors.
AB  - BACKGROUND: Cardiovascular risk factors (CVRFs) may complicate optimization of
      therapy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled
      with oral antidiabetes drugs (OADs). We assessed the influence of patient
      baseline CVRFs on efficacy and rate of hypoglycemia with use of insulin glargine
      (glargine) added to ongoing OAD treatment compared with alternative therapeutic
      options; namely, intensification of lifestyle interventions or adding OADs,
      neutral protamine Hagedorn (NPH), lispro, or premixed insulin in patients failing
      OADs. METHODS: Patient-level data were pooled from 9 randomized controlled trials
      of glargine and comparators for 24 weeks in insulin-naive patients with T2DM
      inadequately controlled on OADs. Efficacy (goal attainment-glycated hemoglobin
      (HbA1c) level <= 7.0% or decrease >= 1.0% change from baseline) and hypoglycemia
      rates (symptomatic, confirmed, nocturnal, or severe) were compared for patients
      treated with glargine (n = 1462) and pooled (n = 1476) and individual
      comparators, overall; and in patients with hypertension (~69%), dyslipidemia
      (~58%), history of cardiovascular disease (~25%), or any CVRF (~83%) at baseline.
      RESULTS: The patient groups were well-balanced at baseline (HbA1c level 8.7%;
      diabetes duration, 8.6 years). Use of glargine was associated with greater
      patient goal attainment (57.7% vs 51.4% for HbA1c level <= 7.0%; P < 0.001),
      modestly larger reductions in HbA1c level (-1.68% vs -1.51%; P < 0.001), and less
      symptomatic hypoglycemia than occurred with pooled comparators, regardless of
      patient CVRFs (5.04 vs 7.01 events/patient-year of exposure, respectively; P <
      0.001). Reductions in HbA1c level and hypoglycemia rates were significantly
      greater with glargine use than with intensification of OADs or lifestyle
      modifications, overall, and in patients with any CVRF. Reductions in HbA1c level
      were greater and hypoglycemia rates lower with use of glargine compared with
      premixed insulin, overall, and in patients with any CVRF. Reductions in HbA1c
      level were similar and hypoglycemia rates lower with use of glargine, NPH, and
      lispro insulin, regardless of patient CVRFs. CONCLUSION: The glycemic benefits of
      glargine use compared with alternative therapeutic options are maintained without
      excess hypoglycemia in patients with CVRFs.

PMID- 24918803
TI  - Understanding the type 2 diabetes mellitus and cardiovascular disease risk
      paradox.
AB  - Patients with diabetes have approximately a 2-fold increase in the risk for
      coronary heart disease, stroke, and death from vascular causes compared with
      patients who do not have diabetes. Interventions targeted at modifiable risk
      factors, such as smoking cessation and management of hypertension and
      dyslipidemia, reduce the risk of cardiovascular disease (CVD) in patients with
      type 2 diabetes mellitus (T2DM). Paradoxically, large randomized studies have
      failed to conclusively show that intensively lowering glucose reduces CVD event
      rates in patients with T2DM, despite pathophysiologic and epidemiologic evidence
      suggesting that hyperglycemia contributes to CVD. Although initiation of
      intensive glycemic control early in the disease course may be associated with a
      reduction in the long-term risk of cardiovascular (CV) events, this approach in
      those with long-standing or complicated T2DM is not of clear benefit and may even
      be harmful in some. Failure to mitigate risk with antihyperglycemic therapy and
      the potential for some treatments to increase CVD risk underlies a treatment
      paradox. New glucose-lowering therapies are now subject to close scrutiny for CV
      safety before and after drug approval. Results from the first trials designed to
      meet the recent CV regulatory requirements have shown no increased risk of major
      adverse CV events but also no CV benefit from dipeptidyl peptidase-4 inhibitor
      therapy, as well as a potentially increased risk of hospitalization for heart
      failure. Conclusive evidence of CV risk reduction with glucose-lowering therapy
      is still lacking and scrutiny of additional agents is necessary. Type 2 diabetes
      mellitus is a heterogeneous disease, for which patient-centered, individualized
      care, and goal-setting is appropriate. Interventions that focus on the management
      of CV risk factors and glucose lowering with medications that are not cardiotoxic
      represent an optimal and attainable treatment approach. 

PMID- 24918804
TI  - Real-world effectiveness of sitagliptin as add-on therapy in patients with type 2
      diabetes mellitus.
AB  - AIMS: To assess the effectiveness of sitagliptin in glycemic control in a
      clinical practice. METHODS: This was a retrospective medical chart review study
      conducted in a single hospital. A total of 3081 patients with diabetes mellitus
      who were prescribed sitagliptin were selected, including 2729 continuous
      sitagliptin users (defined as continuous usage >= 24 weeks) and 352 subjects who
      used sitagliptin for < 24 weeks. An additional 12-month observation period was
      monitored after initiating sitagliptin to extract clinical information at 3, 6,
      9, and 12 months through patient medical chart review. RESULTS: In the 2729
      continuous users, a baseline glycated hemoglobin (HbA1c) level of 9.0% was
      reduced to 8.1%, 8.1%, 8.1%, and 8.2% at 3, 6, 9, and 12 months, respectively,
      representing a 0.9% HbA1c level reduction at 3, 6, and 9 months and a 0.8% HbA1c
      level reduction at 12 months. With a goal of HbA1c value of < 7.0%, 9.1% of the
      patients were under control at baseline; after initiating sitagliptin, 22.7% of
      the patients achieved the HbA1c level goal at 3 months, 23.6% at 6 months, 20.8%
      at 9 months, and 20.4% at 12 months. The proportion of patients attaining the
      goal of HbA1c level < 7.0% at least doubled at different time points after
      treatment with sitagliptin. CONCLUSIONS: In this single-hospital retrospective
      chart analysis, a meaningful clinical improvement in glycemic control before and
      after sitagliptin treatment commenced, including HbA1c level reduction and the
      HbA1c goal attainment rate, was observed. The results reflect the actual clinical
      practice in a large hospital in Taiwan, and supplement data from randomized
      controlled trials.

PMID- 24918805
TI  - Patients' journeys to a narcolepsy diagnosis: a physician survey and
      retrospective chart review.
AB  - Narcolepsy is a lifelong disorder with potentially debilitating symptoms.
      Obtaining an accurate diagnosis often requires multiple tests and physician
      visits. This report describes results from an online, quantitative, company
      sponsored survey in which physicians provided information from the charts of
      their patients with narcolepsy. Neurologists, pulmonologists, psychiatrists, and
      other specialists who were board certified in sleep medicine; had 2 to 30 years
      of clinical experience; and treated >= 5 narcolepsy patients per month were
      invited to complete <= 6 surveys using charts of patients who were treated for
      narcolepsy in the last 6 months. Data from 252 patients were collected from 77
      physicians. Patients were predominantly male (55%), white (67%), and had a median
      age of 38 years (range: 12-83 years). Referral to the respondent physician was
      common, mainly from primary care physicians. The most common initial symptoms
      were excessive daytime sleepiness (91%), trouble staying awake during the day
      (44%), and trouble concentrating/functioning during the day (43%). Overall,
      initial symptoms were of at least moderate severity in 85% of patients. Most
      patients completed overnight polysomnography (83%), a Multiple Sleep Latency Test
      (76%), and/or the Epworth Sleepiness Scale (62%). The median time from patient
      reported symptom onset to diagnosis was 22 months (range: 0-126 months); at least
      half saw >= 2 providers before being diagnosed; and 60% of patients had
      previously been misdiagnosed with other disorders, including depression (31%),
      insomnia (18%), and/or obstructive sleep apnea (13%). In this study, the journey
      to a narcolepsy diagnosis required evaluation by multiple physicians and took
      nearly 2 years in 50% of patients, and > 5 years in 18%. These data highlight the
      need for increased awareness of the signs and symptoms of narcolepsy. 

PMID- 24918806
TI  - Comparison of midazolam and propofol for sedation in pediatric diagnostic imaging
      studies.
AB  - OBJECTIVE: This study aims to compare the efficacy of propofol and midazolam in
      terms of adverse effect potentials and to determine the appropriate strategy for
      pediatric procedural sedation. METHODS: A total of 200 pediatric patients (aged <
      14 years) undergoing diagnostic procedures were recruited for this nonrandomized
      prospective controlled cohort study. The patients were assigned to 2 treatment
      arms: either propofol (Group 1: IV bolus dose of 2 mg/kg during a 2-minute
      period, IV maintenance dose of 100 mcg/kg/min) or midazolam (Group 2: IV bolus
      dose of 0.15 mg/kg during a period of 2 to 3 minutes) to achieve sedation.
      Demographic data, body weight, and clinical status of the patients were evaluated
      and recorded. The vital signs and sedation levels (ie, Ramsay sedation scale
      scores) were evaluated and recorded, as well as the complications detected and
      medications administered in 10-minute intervals throughout the sedation
      procedure. Findings between the study arms were compared. RESULTS: Arterial blood
      pressures decreased significantly in both groups (P = 0.001). The patients in
      Group 1 experienced a greater difference in diastolic blood pressure (P = 0.001)
      than those in Group 2. Sedation scores in Group 1 were more favorable (P = 0.014)
      and reached the appropriate sedation level in a shorter time than those in Group
      2 (P = 0.010). Likewise, recovery time of patients was shorter in Group 1 than in
      Group 2 (P = 0.010). Hypoxia was found to be more common in the propofol group,
      but the difference was not significant (P = 0.333). CONCLUSION: Propofol seems to
      be more effective, achieve the appropriate sedation level more quickly, and
      provide a faster onset of sedation than midazolam in pediatric procedural
      sedation and analgesia. Propofol is preferred for imaging studies (computed
      tomography and magnetic resonance imaging) to reduce the occurrence of undesired
      motion artefacts. Although both drugs are safe to use for sedation before
      pediatric imaging procedures, propofol is preferred with appropriate preparation.

PMID- 24918807
TI  - Influence of HMG-CoA reductase inhibitors on leptin-induced endothelial cell
      proliferation, migration, and capillary-like tube formation.
AB  - OBJECTIVE: This study investigated the impact of the hepatic
      hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on the
      leptin-induced human umbilical vein endothelial (HUVE) cell proliferation,
      migration, and capillary-like tube formation. METHODS: The HUVE cells were
      isolated and cultured, and stimulated with leptin, statins (cerivastatin,
      fluvastatin, simvastatin), mevalonate, farnesyl pyrophosphate, geranylgeranyl
      pyrophosphate, or methyl-beta-cyclodextrin. The endothelial cell proliferation
      was assessed using the Neubauer counting chamber. The migration of HUVE cells was
      examined with the planar migration assay. In vitro capillary sprouting was
      quantified by measuring the sprout length, number, and cumulative sprout length.
      RESULTS: The HMG-CoA reductase inhibitors significantly reduced leptin-induced
      proliferation and migration, which was reversed by mevalonate. Further, the
      inhibitory effect of the statins on leptin-induced migration was shown to be
      modulated by the prenylation of farnesyl pyrophosphate and geranylgeranyl
      pyrophosphate. Although stimulation with a leptin showed no significant effect, a
      marked increase in capillary-like tube formation was observed with a joint
      stimulation with HMG-CoA reductase inhibitors. Although statins caused inhibition
      of proliferation and migration, the same dose of the agents amplified the
      selective growth of capillary-like tube formation. Membranous cholesterol
      depletion by methyl-beta-cyclodextrin showed a weaker effect compared with
      statins. CONCLUSION: Through modulation of prenylation, leptin-induced pro
      atherosclerotic events including proliferation and migration were inhibited by
      HMG-CoA reductase inhibitors.

PMID- 24918808
TI  - Proton-pump inhibitors in patients requiring antiplatelet therapy: new FDA
      labeling.
AB  - Proton-pump inhibitors (PPIs) are recommended for patients who require
      antiplatelet therapy and have a history of upper gastrointestinal bleeding.
      Proton-pump inhibitors should also be considered for patients receiving
      antiplatelet therapy who have other risk factors for gastrointestinal bleeding,
      including use of aspirin. Thus, evidence of pharmacokinetic and pharmacodynamic
      interactions between PPIs and consequent impaired effectiveness of the
      antiplatelet agent clopidogrel has caused concern. Here, we discuss comparative
      studies suggesting that the extent to which a PPI reduces exposure to the active
      metabolite of clopidogrel and attenuates its antithrombotic effect differs among
      PPIs. Although a clinically meaningful effect of the interaction between PPIs and
      clopidogrel on cardiovascular outcomes has not been established, these studies
      provided the basis for recent changes in US Food and Drug Administration (FDA)
      labeling for several PPIs and clopidogrel. New labeling suggests that PPI use
      among patients taking clopidogrel be limited to pantoprazole, rabeprazole,
      lansoprazole, or dexlansoprazole. Because comparative studies indicate that
      omeprazole and esomeprazole have a greater effect on the CYP2C19-mediated
      conversion of clopidogrel to its active metabolite and, consequently,
      clopidogrel's effect on platelet reactivity, FDA labeling recommends avoiding
      omeprazole and esomeprazole in patients taking clopidogrel. Even a 12-hour
      separation of dosing does not appear to prevent drug interactions between
      omeprazole and clopidogrel. 

PMID- 24918809
TI  - Fesoterodine prescription fill patterns and evaluation of the YourWay patient
      support plan for patients with overactive bladder symptoms and physicians.
AB  - BACKGROUND: Adherence with oral medication for overactive bladder syndrome is
      suboptimal. To improve adherence, the YourWay plan was developed to assist
      patients and health care providers in defining treatment expectations and
      facilitating communication. OBJECTIVE: To evaluate medication adherence among
      patients with overactive bladder syndrome enrolled in the YourWay patient support
      plan, patient adoption of behavioral interventions, patient satisfaction with the
      plan, and physician experience with the plan. METHODS: In this 13-week, single
      arm, open-label, multicenter, noninterventional study, fesoterodine-naive
      patients received a prescription for fesoterodine 4 or 8 mg and a packet
      including a 14-day fesoterodine sample, educational materials, and progress
      tracker. Patients registered for the YourWay plan, which included an educational
      resource kit, interactive voice-response calls, and optional online and mail
      support. The primary end point was the proportion of patients who filled a
      prescription for a >= 90-day supply of fesoterodine within 90 days of enrollment.
      Secondary end points were the proportion of patients who filled >= 1 prescription
      and >= 2 prescriptions (post hoc), patient evaluation of their experience and
      satisfaction with the YourWay plan, and differences between prescription fillers
      and nonfillers in plan adoption and assessment (post hoc). We surveyed an
      independent sample of physicians to assess their experience with YourWay.
      RESULTS: Of 500 study completers, 10.4% filled a prescription for a >= 90-day
      supply of fesoterodine. Of those filling a prescription, 26.2% filled >= 1
      prescription and among those, 61.0% refilled their prescription at least once.
      Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers
      were more likely to take fesoterodine as directed, whereas adoption of behavioral
      recommendations or plan satisfaction did not differ between fillers and
      nonfillers. Most patients reported that the plan was informative and feasible to
      implement, and that they were satisfied with various aspects of the plan.
      Physicians also reported positive experiences. CONCLUSION: Most patients adopted
      YourWay components and viewed the plan positively, although adherence remained a
      challenge.

PMID- 24918810
TI  - Physician adherence to ACR gout treatment guidelines: perception versus practice.
AB  - BACKGROUND: In October 2012, the American College of Rheumatology (ACR) published
      recommendations for chronic gout treatment goals and pharmacotherapy. OBJECTIVES:
      Identify potential gaps between real-world chronic gout treatment, ACR guideline
      recommendations, and physicians' perceived guideline adherence by evaluating
      records of patients classified as having "higher" and "lower" guideline adherence
      as defined by the investigators. METHODS: A comprehensive quantitative survey was
      administered between February 11 and February 22, 2013, to physicians treating
      patients with gout; the survey included a patient record chart review informed by
      prior qualitative interviews. Eight criteria from the ACR gout management
      guidelines were used to compose the survey. To assess ACR guideline adherence,
      information from records of patients with chronic gout treated by primary care
      physicians (PCPs) and rheumatologists was scored from 0 (no adherence) to 8
      (total adherence), in accordance with ACR guideline recommendations. Physicians
      also indicated how closely they believed patient treatment followed current
      guidelines on a 10-point scale. RESULTS: Of the 350 records of patients with
      chronic gout, all but 3 PCP patients were adherent on >= 1 guideline
      recommendation, but nearly all patients could be considered nonadherent,
      considering all potential recommendations. Patients with chronic gout treated by
      rheumatologists tended to be managed more closely to ACR guidelines than patients
      treated by PCPs (mean scores: rheumatologists 5.8/8 +/- 1.7 vs 4.3/8 +/- 1.7 for
      PCPs). Among patients classified as having "higher adherence" based on adherence
      scores, there was low adherence on first-line urate lowering therapy dose, acute
      prophylaxis dosing, and length of prophylaxis treatment. Among PCPs and
      rheumatologists, there was a disparity between how closely physicians believed
      patient treatment followed guidelines and actual adherence with ACR guidelines
      based on adherence scores. For 16.4% of patients treated by PCPs and 18.4% of
      patients seen by rheumatologists, physicians believed they closely followed ACR
      guidelines (score of 8-10/10) for each patient; but in actuality, adherence was
      lower. CONCLUSION: Although adherence with ACR guidelines is higher among
      rheumatologists than PCPs in treating patients with gout, overall adherence could
      be improved by both specialties.

PMID- 24918811
TI  - Assessment of aerobic and respiratory growth in the Lactobacillus casei group.
AB  - One hundred eighty four strains belonging to the species Lactobacillus casei, L.
      paracasei and L. rhamnosus were screened for their ability to grow under aerobic
      conditions, in media containing heme and menaquinone and/or compounds generating
      reactive oxygen species (ROS), in order to identify respiratory and oxygen
      tolerant phenotypes. Most strains were able to cope with aerobic conditions and
      for many strains aerobic growth and heme or heme/menaquinone supplementation
      increased biomass production compared to anaerobic cultivation. Only four L.
      casei strains showed a catalase-like activity under anaerobic, aerobic and
      respiratory conditions and were able to survive in presence of H2O2 (1 mM).
      Almost all L. casei and L. paracasei strains tolerated menadione (0.2 mM) and
      most tolerated pyrogallol (50 mM), while L. rhamnosus was usually resistant only
      to the latter compound. This is the first study in which an extensive screening
      of oxygen and oxidative stress tolerance of members of the L. casei group has
      been carried out. Results allowed the selection of strains showing the typical
      traits of aerobic and respiratory metabolism (increased pH and biomass under
      aerobic or respiratory conditions) and unique oxidative stress response
      properties. Aerobic growth and respiration may confer technological and
      physiological advantages in the L. casei group and oxygen-tolerant phenotypes
      could be exploited in several food industry applications. 

PMID- 24918812
TI  - Phylogenetic stochastic mapping without matrix exponentiation.
AB  - Phylogenetic stochastic mapping is a method for reconstructing the history of
      trait changes on a phylogenetic tree relating species/organism carrying the
      trait. State-of-the-art methods assume that the trait evolves according to a
      continuous-time Markov chain (CTMC) and works well for small state spaces. The
      computations slow down considerably for larger state spaces (e.g., space of
      codons), because current methodology relies on exponentiating CTMC infinitesimal
      rate matrices-an operation whose computational complexity grows as the size of
      the CTMC state space cubed. In this work, we introduce a new approach, based on a
      CTMC technique called uniformization, which does not use matrix exponentiation
      for phylogenetic stochastic mapping. Our method is based on a new Markov chain
      Monte Carlo (MCMC) algorithm that targets the distribution of trait histories
      conditional on the trait data observed at the tips of the tree. The computational
      complexity of our MCMC method grows as the size of the CTMC state space squared.
      Moreover, in contrast to competing matrix exponentiation methods, if the rate
      matrix is sparse, we can leverage this sparsity and increase the computational
      efficiency of our algorithm further. Using simulated data, we illustrate
      advantages of our MCMC algorithm and investigate how large the state space needs
      to be for our method to outperform matrix exponentiation approaches. We show that
      even on the moderately large state space of codons our MCMC method can be
      significantly faster than currently used matrix exponentiation methods.

PMID- 24918814
TI  - Glyoxalase I inhibition induces apoptosis in irradiated MCF-7 cells via a novel
      mechanism involving Hsp27, p53 and NF-kappaB.
AB  - BACKGROUND: Glyoxalase I (GI) is a cellular defence enzyme involved in the
      detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis, and MG
      derived advanced glycation end products (AGEs). Argpyrimidine (AP), one of the
      major AGEs coming from MG modifications of proteins arginines, is a pro-apoptotic
      agent. Radiotherapy is an important modality widely used in cancer treatment.
      Exposure of cells to ionising radiation (IR) results in a number of complex
      biological responses, including apoptosis. The present study was aimed at
      investigating whether, and through which mechanism, GI was involved in IR-induced
      apoptosis. METHODS: Apoptosis, by TUNEL assay, transcript and protein levels or
      enzymatic activity, by RT-PCR, western blot and spectrophotometric methods,
      respectively, were evaluated in irradiated MCF-7 breast cancer cells, also in
      experiments with appropriate inhibitors or using small interfering RNA. RESULTS:
      Ionising radiation induced a dramatic reactive oxygen species (ROS)-mediated
      inhibition of GI, leading to AP-modified Hsp27 protein accumulation that, in a
      mechanism involving p53 and NF-kappaB, triggered an apoptotic mitochondrial
      pathway. Inhibition of GI occurred at both functional and transcriptional levels,
      the latter occurring via ERK1/2 MAPK and ERalpha modulation. CONCLUSIONS:
      Glyoxalase I is involved in the IR-induced MCF-7 cell mitochondrial apoptotic
      pathway via a novel mechanism involving Hsp27, p53 and NF-kappaB.

PMID- 24918813
TI  - Characterisation of familial colorectal cancer Type X, Lynch syndrome, and non
      familial colorectal cancer.
AB  - BACKGROUND: Familial Colorectal Cancer Type X (FCCTX) is defined as individuals
      with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but
      whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS).
      FCCTX does not have an increased risk of extra-colonic cancers. This analysis
      compares epidemiologic and clinicopathologic features among FCCTX, LS, and 'non
      familial' (non-AC1) CRC cases. METHODS: From the Colon Cancer Family Registry,
      FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified.
      Questionnaire-based epidemiologic information and CRC pathologic features were
      compared across case groups using polytomous logistic regression. RESULTS:
      Compared with LS, FCCTX cases were less likely to be current (vs never) smokers;
      have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor
      differentiation, or tumour-infiltrating lymphocytes. There were no observed
      differences in co-morbidities or medication usage. CONCLUSIONS: FCCTX were less
      likely to be current tobacco users; other exposures were similar between these
      groups. Histopathologic differences highly suggestive of LS CRCs do not appear to
      be shared by FCCTX.

PMID- 24918815
TI  - The role of patient, tumour and system factors in socioeconomic inequalities in
      lung cancer treatment: population-based study.
AB  - BACKGROUND: Reducing socioeconomic inequalities in lung cancer treatment may
      reduce survival inequalities. However, the reasons for treatment variation are
      unclear. METHODS: Northern and Yorkshire cancer registry, Hospital Episode
      Statistics and lung cancer audit data sets were linked. Logistic regression was
      used to explore the role of stage, histology, performance status and comorbidity
      in socioeconomic inequalities in lung cancer treatment, for 28,733 lung cancer
      patients diagnosed in 2006-2010, and in a subgroup with stage recorded (n=7769,
      27%). RESULTS: Likelihood of receiving surgery was significantly lower in the
      most deprived group (odds ratio (OR)=0.75, 95% confidence interval (CI) 0.65
      0.86); however, the OR was attenuated when including histological subtype
      (OR=0.82, 95% CI 0.71-0.96). Patients in the most deprived group were
      significantly less likely to receive chemotherapy in the fully adjusted full
      cohort model including performance status (OR=0.64, 95% CI 0.58-0.72) but not in
      the staged subgroup model when performance status was included (OR=0.88, 95% CI
      0.72-1.08). Socioeconomic inequalities in radiotherapy were not found.
      INTERPRETATION: Socioeconomic inequalities in performance status statistically
      explained socioeconomic inequalities in receipt of chemotherapy in the selective
      staged subgroup, but not in the full cohort. Socioeconomic variation in
      histological subtype may account for some of the socioeconomic inequalities in
      surgery.

PMID- 24918816
TI  - Prognostic factors in elderly patients with malignant pleural mesothelioma:
      results of a multicenter survey.
AB  - BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) in elderly
      patients is increasing. There are no specific guidelines for their management.
      METHODS: The clinical records of elderly patients (?70 years old) with MPM
      referred from January 2005 to November 2011 to six Italian Centres were reviewed.
      Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage,
      Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson
      Comorbidity Index (CCI) and treatment modalities were analysed and correlated to
      overall survival (OS). RESULTS: In total, 241 patients were identified. Charlson
      Comorbidity Index was ?1 in 92 patients (38%). Treatment was multimodality
      therapy including surgery in 18, chemotherapy alone in 180 (75%) and best
      supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based.
      Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66-3.23,
      P<0.001), age ?75 years (HR 1.44; 95% CI 1.08-1.93, P=0.014), advanced (III-IV)
      stage (HR 1.47; 95% CI 1.09-1.98, P=0.011) and CCI?1 (HR 1.38; 95% CI 1.02-1.85,
      P=0.034) were associated to a shorter OS. Treatment with pemetrexed was
      associated with improved OS (HR 0.40; 95% CI 0.28-0.56, P<0.001). CONCLUSIONS:
      Non-epithelioid histology, age ?75 years, advanced IMIG stage and presence of
      comorbidities according to CCI were significant prognostic factors in elderly
      patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in
      this setting. Prospective dedicated trials in MPM elderly patients selected
      according to prognostic factors including comorbidity scales are warranted.

PMID- 24918818
TI  - Vitamin D supplements and cancer incidence and mortality: a meta-analysis.
AB  - BACKGROUND: Observational studies suggest that effects of vitamin D may be
      stronger for cancer mortality than for incidence. Yet, existing randomised
      controlled trials (RCTs) of vitamin D supplementation have limited power to
      examine the relationships as their primary end points are not cancer incidence or
      mortality. METHODS: Meta-analyses of RCTs of vitamin D supplementation and total
      cancer incidence and mortality were conducted. RESULTS: Over 2-7 years of
      duration, vitamin D supplementations had little effect on total cancer incidence
      (400-1100 IU per day, summary relative risk (RR)=1.00, 95% confidence interval
      (CI)=0.94-1.06, I(2)=0%; four RCTs with combined 4333 cases), but significantly
      reduced total cancer mortality (400-833 IU per day, summary RR=0.88, 95% CI=0.78
      0.98, I(2)=0%, three RCTs with combined 1190 deaths). CONCLUSIONS: Over 2-7 years
      of duration, the benefit of vitamin D supplementation may be limited to cancer
      mortality.

PMID- 24918819
TI  - Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in
      patients undergoing radical cystectomy for urothelial carcinoma of the bladder.
AB  - BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with
      poor outcome in various tumours. Its prognostic utility in patients with
      urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is
      yet to be fully elucidated. METHODS: A cohort of patients undergoing RC for UCB
      in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to
      lymphocyte ratio was computed using complete blood counts performed pre-RC, or
      before neo-adjuvant chemotherapy where applicable. Time-dependent receiver
      operating characteristic curves were used to determine the optimal cutoff point
      for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and
      overall survival (OS). The predictive ability of NLR was assessed using Kaplan
      Meier analyses and multivariable Cox proportional hazards models. The likelihood
      ratio test was used to determine whether multivariable models were improved by
      including NLR. RESULTS: The cohort included 424 patients followed for a median of
      58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients
      with an NLR?3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%,
      log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log
      rank P<0.001). After adjusting for disease-specific predictors, an NLR ?3.0 was
      significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS
      (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39,
      P=0.005). The likelihood-ratio test confirmed that prognostic models were
      improved by including NLR. CONCLUSIONS: Neutrophil-to-lymphocyte ratio is an
      inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers
      pre-treatment prognostic value in addition to established prognosticators and may
      be helpful in guiding treatment decisions.

PMID- 24918817
TI  - No socioeconomic inequalities in ovarian cancer survival within two randomised
      clinical trials.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death among cancers of the
      female genital tract, with poor outcomes despite chemotherapy. There was a
      persistent socioeconomic gradient in 1-year survival in England and Wales for
      more than 3 decades (1971-2001). Inequalities in 5-year survival persisted for
      more than 20 years but have been smaller for women diagnosed around 2000. We
      explored one possible explanation. METHODS: We analysed data on 1406 women
      diagnosed with ovarian cancer during 1991-1998 and recruited to one of two
      randomised clinical trials. In the second International Collaborative Ovarian
      Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to
      receive either the three-drug combination cyclophosphamide, doxorubicin and
      cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3
      trial, women diagnosed during 1995-1998 were randomised to receive either the
      same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1,
      5 and 10 years was estimated for women in five categories of socioeconomic
      deprivation. The excess hazard of death over and above background mortality was
      estimated by fitting multivariable regression models with Poisson error structure
      and a dedicated link function in a generalised linear model framework, adjusting
      for the duration of follow-up and the confounding effects of age, Federation of
      Gynecology and Obstetrics (FIGO) stage and calendar period. RESULTS: Unlike women
      with ovarian cancer in the general population, no statistically significant
      socioeconomic gradient was seen for women with ovarian cancer treated in the two
      randomised controlled trials. The deprivation gap in 1-year relative survival in
      the general population was statistically significant at -6.7% (95% CI (-8.1, 
      5.3)), compared with -3.6% (95% CI (-10.4, +3.2)) in the trial population.
      CONCLUSIONS: Although ovarian cancer survival is significantly lower among poor
      women than rich women in England and Wales, there was no evidence of an
      association between socioeconomic deprivation and survival among women with
      ovarian cancer who were treated and followed up consistently in two well
      conducted randomised controlled trials. We conclude that the persistent
      socioeconomic gradient in survival among women with ovarian cancer, at least for
      1-year survival, may be due to differences in access to treatment and standards
      of care.

PMID- 24918820
TI  - Survival and contralateral breast cancer in CHEK2 1100delC breast cancer
      patients: impact of adjuvant chemotherapy.
AB  - BACKGROUND: We assessed the sensitivity to adjuvant chemotherapy in cell cycle
      checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the
      contralateral breast cancer incidence and distant disease-free and breast cancer
      specific survival between both groups, stratified for adjuvant chemotherapy.
      METHODS: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220)
      and two Dutch cohorts unselected for family history (n=1014 and n=2488,
      respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral
      breast cancer, distant disease-free and breast cancer-specific death for mutation
      carriers vs noncarriers were calculated using the Cox proportional hazard method,
      stratified for adjuvant chemotherapy. RESULTS: The CHEK2 mutation carriers
      (n=193) had an increased incidence of contralateral breast cancer (multivariate
      hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and
      breast cancer-specific survival were similar in the first 6 years in mutation
      carriers compared with noncarriers, but diverted as of 6 years after breast
      cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65
      (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction
      between CHEK2 and adjuvant chemotherapy was observed. CONCLUSIONS: The CHEK2
      1100delC-associated breast cancer is associated with a higher contralateral
      breast cancer rate as well as worse survival measures beyond 6 years after
      diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in
      CHEK2 patients.

PMID- 24918821
TI  - Metadherin regulates proliferation and metastasis via actin cytoskeletal
      remodelling in non-small cell lung cancer.
AB  - BACKGROUND: Metaderin (MTDH) protein is a novel component part of tight junction
      complex. The aim of this study was to investigate the correlation between MTDH
      and prognosis of patients and to explore the role of MTDH on NSCLC development
      and metastasis. METHODS: Relative mRNA expression was evaluated by quantitative
      real-time PCR, and protein expression was detected using immunohistochemistry
      staining. The role of MTDH in cancer cell proliferation, migration and invasion
      was studied by modulation of MTDH expression in NSCLC cell lines. These functions
      of MTDH were further confirmed in vivo. RESULTS: In NSCLC, low MTDH protein
      expression was correlated with lymph node metastasis, TNM stage and decreased OS
      (P=0.001, 0.011 and 0.013, respectively). Overexpression of MTDH reduced
      anchorage-independent and -dependent growth through arresting cell cycle,
      inhibited migration and invasion in vitro and further suppressed tumorigenesis,
      tumour growth and metastasis in vivo. Knockdown of MTDH expression increased cell
      invasiveness. MTDH overexpression reversed pro-metastatic actin cytoskeleton
      remodelling and inhibited EMT, supporting that MTDH has a key role on cancer
      proliferation and metastasis. CONCLUSIONS: MTDH has an important role in NSCLC
      proliferation and metastasis and provides potential in predicting metastasis and
      prognosis for patients with NSCLC.

PMID- 24918825
TI  - The Reno Orthopaedic Clinic trauma business curriculum. Introduction.

PMID- 24918823
TI  - Correlation of BRAF and NRAS mutation status with outcome, site of distant
      metastasis and response to chemotherapy in metastatic melanoma.
AB  - BACKGROUND: The prognostic significance of BRAF and NRAS mutations in metastatic
      melanoma patients remains uncertain, with several studies reporting conflicting
      results, often biased by the inclusion of patients treated with BRAF and MEK
      (MAPK) inhibitors. We therefore interrogated a historical cohort of patients free
      of the confounding influence of MAPK inhibitor therapy. METHODS: Patients with
      available archival tissue first diagnosed with metastatic melanoma between 2002
      and 2006 were analysed. Mutational analysis was performed using the OncoCarta
      Panel. Patient characteristics, treatment outcome and survival were correlated
      with BRAF/NRAS mutation status. RESULTS: In 193 patients, 92 (48%) melanomas were
      BRAF-mutant, 39 (20%) were NRAS-mutant and 62 (32%) were wild-type for BRAF/NRAS
      mutations (wt). There was no difference in response to chemotherapy based on
      mutation status (35-37%). The distant disease-free interval (DDFI) was
      significantly shorter in patients with wt melanoma (27.9 months vs 35.1 for BRAF
      and 49.1 for NRAS) although this was not significant in multivariate analysis.
      Survival from stage IV melanoma diagnosis was not significantly different based
      on mutation status. The DDFI was significantly shorter in patients with
      BRAF(V600K/R) versus BRAF(V600E) melanoma in univariate and multivariate
      analyses. CONCLUSIONS: BRAF and NRAS mutation status does not influence survival
      in metastatic melanoma.

PMID- 24918824
TI  - Risk factors for delay in symptomatic presentation: a survey of cancer patients.
AB  - BACKGROUND: Delay in symptomatic presentation leading to advanced stage at
      diagnosis may contribute to poor cancer survival. To inform public health
      approaches to promoting early symptomatic presentation, we aimed to identify risk
      factors for delay in presentation across several cancers. METHODS: We surveyed
      2371 patients with 15 cancers about nature and duration of symptoms using a
      postal questionnaire. We calculated relative risks for delay in presentation
      (time from symptom onset to first presentation >3 months) by cancer, symptoms
      leading to diagnosis and reasons for putting off going to the doctor, controlling
      for age, sex and deprivation group. RESULTS: Among 1999 cancer patients reporting
      symptoms, 21% delayed presentation for >3 months. Delay was associated with
      greater socioeconomic deprivation but not age or sex. Patients with prostate
      (44%) and rectal cancer (37%) were most likely to delay and patients with breast
      cancer least likely to delay (8%). Urinary difficulties, change of bowel habit,
      systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms
      were all common and associated with delay. Overall, patients with bleeding
      symptoms were no more likely to delay presentation than patients who did not have
      bleeding symptoms. However, within the group of patients with bleeding symptoms,
      there were significant differences in risk of delay by source of bleeding: 35% of
      patients with rectal bleeding delayed presentation, but only 9% of patients with
      urinary bleeding. A lump was a common symptom but not associated with delay in
      presentation. Twenty-eight percent had not recognised their symptoms as serious
      and this was associated with a doubling in risk of delay. Embarrassment, worry
      about what the doctor might find, being too busy to go to the doctor and worry
      about wasting the doctor's time were also strong risk factors for delay, but were
      much less commonly reported (<6%). INTERPRETATION: Approaches to promote early
      presentation should aim to increase awareness of the significance of cancer
      symptoms and should be designed to work for people of the lowest socioeconomic
      status. In particular, awareness that rectal bleeding is a possible symptom of
      cancer should be raised.

PMID- 24918822
TI  - Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous
      cell carcinoma based on microRNA expression signature.
AB  - BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) has a very poor
      prognosis because of its high rates of regional and distant metastasis.
      Identification of differentially expressed miRNAs and their regulated molecular
      targets in tumour cells might enhance our understanding of the molecular
      mechanisms of metastasis in human cancers. METHODS: A HSCC miRNA signature was
      constructed by array-based methods. Functional studies of microRNA-451a (miR
      451a) and target genes were performed to investigate cell proliferation,
      migration and invasion by cancer cell lines. To identify miR-451a-regulated
      molecular targets, we adopted gene expression analysis and in silico database
      analysis. RESULTS: Our miRNA signature revealed that miR-451a was significantly
      downregulated in HSCC. Restoration of miR-451a in cancer cell lines revealed that
      this miRNA significantly inhibited cancer cell migration and invasion. Our data
      demonstrated that the gene coding for endothelial and smooth muscle cell-derived
      neuropilin-like molecule (ESDN/DCBLD2) was a direct target of miR-451a
      regulation. Silencing of ESDN inhibited cell migration and invasion by cancer
      cells. CONCLUSIONS: Loss of tumour suppressive miR-451a enhanced cancer cell
      migration and invasion in HSCC through direct regulation of ESDN. Our miRNA
      signature and functional analysis of targets regulated by tumour suppressive miR
      451a provide new insights into the potential mechanisms of HSCC oncogenesis and
      metastasis.

PMID- 24918826
TI  - Practice management.
AB  - The practicing orthopaedic traumatologist must have a sound knowledge of business
      fundamentals to be successful in the changing healthcare environment. Practice
      management encompasses multiple topics including governance, the financial
      aspects of billing and coding, physician extender management, ancillary service
      development, information technology, transcription utilization, and marketing.
      Some of these are universal, but several of these areas may be most applicable to
      the private practice of medicine. Attention to each component is vital to develop
      an understanding of the intricacies of practice management.

PMID- 24918828
TI  - Healthcare fundamentals.
AB  - In order for a trauma surgeon to have an intelligent discussion with hospital
      administrators, healthcare plans, policymakers, or any other physicians, a basic
      understanding of the fundamentals of healthcare is paramount. It is truly
      shocking how many surgeons are unable to describe the difference between Medicare
      and Medicaid or describe how hospitals and physicians get paid. These topics may
      seem burdensome but they are vital to all business decision making in the
      healthcare field. The following chapter provides further insight about what we
      call "the basics" of providing medical care today. Most of the topics presented
      can be applied to all specialties of medicine. It is broken down into 5 sections.
      The first section is a brief overview of government programs, their influence on
      care delivery and reimbursement, and past and future legislation. Section 2
      focuses on the compliance, care provision, and privacy statutes that regulate
      physicians who care for Medicare/Medicaid patient populations. With a better
      understanding of these obligations, section 3 discusses avenues by which
      physicians can stay informed of current and pending health policy and provides
      ways that they can become involved in shaping future legislation. The fourth
      section changes gears slightly by explaining how the concepts of trade restraint,
      libel, antitrust legislation, and indemnity relate to physician practice. The
      fifth, and final, section ties all of components together by describing how
      physician-hospital alignment can be mutually beneficial in providing patient care
      under current healthcare policy legislation.

PMID- 24918827
TI  - Hospital fundamentals.
AB  - Under the current system, orthopaedic trauma surgeons must work in some form of
      hospital setting as our primary service involves treatment of the trauma patient.
      We must not forget that just as a trauma center cannot exist without our
      services, we cannot function without their support. As a result, a clear
      understanding of the balance between physicians and hospitals is paramount.
      Historical perspective enables physicians and hospital personnel alike to
      understand the evolution of hospital-physician relationship. This process should
      be understood upon completion of this chapter. The relationship between
      physicians and hospitals is becoming increasingly complex and multiple forms of
      integration exist such as joint ventures, gain sharing, and co-management
      agreements. For the surgeon to negotiate well, an understanding of hospital
      governance and the role of the orthopaedic traumatologist is vital to success. An
      understanding of the value provided by the traumatologist includes all aspects of
      care including efficiency, availability, cost effectiveness, and research
      activities. To create effective and sustainable healthcare institutions,
      physicians and hospitals must be aligned over a sustained period of time.
      Unfortunately, external forces have eroded the historical basis for the working
      relationship between physicians and hospitals. Increased competition and
      reimbursement cuts, coupled with the increasing demands for quality, efficiency,
      and coordination and the payment changes outlined in healthcare reform, have left
      many organizations wondering how to best rebuild the relationship. The principal
      goal for the physician when partnering with a hospital or healthcare entity is to
      establish a sustainable model of service line management that protects or
      advances the physician's ability to make impactful improvements in quality of
      patient care, decreases in healthcare costs, and improvements in process
      efficiency through evidence-based practices and protocols.

PMID- 24918829
TI  - Reno Orthopaedic Trauma Fellowship business curriculum.
AB  - The Reno Orthopaedic Center (ROC) Trauma Fellowship business curriculum is
      designed to provide the fellow with a graduate level business practicum and
      research experience. The time commitments in a typical 12-month trauma fellowship
      are significant, rendering a traditional didactic master's in business
      administration difficult to complete during this short time. An organized,
      structured, practical business education can provide the trauma leaders of
      tomorrow with the knowledge and experience required to effectively navigate the
      convoluted and constantly changing healthcare system. The underlying principle
      throughout the curriculum is to provide the fellow with the practical knowledge
      to participate in cost-efficient improvements in healthcare delivery. Through the
      ROC Trauma Fellowship business curriculum, the fellow will learn that delivering
      healthcare in a manner that provides better outcomes for equal or lower costs is
      not only possible but a professional and ethical responsibility. However,
      instilling these values without providing actionable knowledge and programs would
      be insufficient and ineffective. For this reason, the core of the curriculum is
      based on individual teaching sessions with a wide array of hospital and private
      practice administrators. In addition, each section is equipped with a suggested
      reading list to maximize the learning experience. Upon completion of the
      curriculum, the fellow should be able to: (1) Participate in strategic planning
      at both the hospital and practice level based on analysis of financial and
      clinical data, (2) Understand the function of healthcare systems at both a macro
      and micro level, (3) Possess the knowledge and skills to be strong leaders and
      effective communicators in the business lexicon of healthcare, (4) Be a partner
      and innovator in the improvement of the delivery of orthopaedic services, (5)
      Combine scientific and strategic viewpoints to provide an evidence-based strategy
      for improving quality of care in a cost-efficient manner, (6) Understand the
      political, economic, and strategic basics of private practice orthopaedics.

PMID- 24918830
TI  - Trauma program development.
AB  - The development of a strong trauma program is clearly one of the most important
      facets of successful business development. Several recent publications have
      demonstrated that well run trauma services can generate significant profits for
      both the hospital and the surgeons involved. There are many aspects to this task
      that require constant attention and insight. Top notch patient care, efficiency,
      and cost-effective resource utilization are all important components that must be
      addressed while providing adequate physician compensation within the bounds of
      hospital financial constraints and the encompassing legal issues. Each situation
      is different but many of the components are universal. This chapter addresses all
      aspects of trauma program development to provide the graduating fellow with the
      tools to create a new trauma program or improve an existing program in order to
      provide the best patient care while optimizing financial reward and improving
      care efficiency.

PMID- 24918831
TI  - Hospital support.
AB  - Setting up a successful trauma system requires a significant amount of hospital
      support. This includes personnel and programs to assist with quality assurance
      programs, clinical compliance, and rural support and development. It is
      imperative that orthopaedic trauma surgeons are well versed in the types of
      hospital support available and the costs associated with each support measure.
      With this understanding, a strong, sustainable physician-hospital relationship
      can be created.

PMID- 24918832
TI  - Personal finances for the physician: a primer on maintaining and protecting your
      earnings.
AB  - Personal finance is a key component to your success as a physician. Your clinical
      practice does not exist in a vacuum unaffected by circumstances and decisions in
      your personal life. Though some events in your personal life that can negatively
      affect your practice are random and unavoidable, consistently making sound
      decisions regarding your personal life and finances will allow you to continue
      practicing at a high level. Most core principles of personal finance are common
      sense and do not involve high level math. Although the concepts are
      straightforward, people, including physicians, routinely fail to make good
      decisions at the most elementary level. The core common sense principles for
      financial success are: do not get divorced, manage your own money, live in a
      state without state income tax, and drive an old car. Follow these tenants and
      the path to successful and satisfactory retirement will be smooth.

PMID- 24918833
TI  - Questionnaires for outcome expectancy, self-regulation, and behavioral
      expectation for resistance training among young-old adults: development and
      preliminary validity.
AB  - The purpose of the present research was to develop questionnaires to assess
      outcome expectancy for resistance training (RT), behavioral expectation in the
      context of perceived barriers to RT, and self-regulation strategies for RT among
      young-old adults (50-69 years). Measurement development included (a) item
      generation through elicitation interviews (N = 14) and open-ended questionnaires
      (N = 56), (b) expert feedback on a preliminary draft of the questionnaires (N =
      4), and (c) a quantitative longitudinal study for item-reduction and psychometric
      analyses (N = 94). Elicitation procedures, expert feedback, and item reduction
      yielded four questionnaires with a total of 33 items. Positive outcome expectancy
      (alpha = .809), negative outcome expectancy (alpha = .729), behavioral
      expectation (alpha = .925), and self-regulation (alpha = .761) had-with one
      exception-moderate bivariate associations with two different indicators of self
      reported RT behavior at one-month follow-up (r = .298 to .506). The present
      research provides preliminary support for newly developed questionnaires to
      facilitate understanding of the psychosocial determinants of RT among young-old
      adults. 

PMID- 24918834
TI  - Belinostat for the treatment of peripheral T-cell lymphomas.
AB  - Belinostat is a novel histone deacetylase (HDAC) inhibitor that is being
      developed in various solid tumors and hematologic malignancies. HDACs have been
      found to be important in the epigenetic regulation of cancer progression and
      inhibition of these molecules in preclinical studies induces cancer cell
      apoptosis and prevents tumor growth. Several HDAC molecules have been found to be
      overexpressed in peripheral T-cell lymphoma (PTCL) and therefore HDAC inhibition
      has been an important new target in treating these malignancies which have
      traditionally had poor outcomes and limited treatment response. Phase I studies
      were tested across a broad range of hematologic and solid tumors and showed
      stability of disease in various tumor types with low rates of adverse events.
      This made it acceptable to proceed with further testing in specific tumor types
      to further determine efficacy. Two phase II studies have been completed with
      belinostat given intravenously in the relapsed/refractory PTCL setting with at
      least 25% overall response and minimal toxicities. These findings have led to a
      request for accelerated approval to the U.S. Food and Drug Administration for
      belinostat in this setting. This review will discuss the preclinical
      pharmacology, pharmacokinetics and clinical efficacy to date of belinostat in the
      treatment of PTCL. 

PMID- 24918835
TI  - Nalmefene and its use in alcohol dependence.
AB  - Nalmefene is the first available drug approved in the E.U. to reduce alcohol use
      in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers
      diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy
      at 6 months in alcohol-dependent patients with high or very high drinking risk
      levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval
      (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI:
      -3.00 to -1.00]; P ? 0.00001) and other secondary outcome measures such as gamma
      glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical
      Global Impression. It is generally well tolerated and has limited
      contraindications and interactions. As-needed dosage is a novel concept in the
      addictions field, which may overcome limitations of traditional regimens. In the
      pivotal trials, nalmefene was taken 52% of the days and compliance with the as
      needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene
      treated patients. A new pharmacological approach combined with a brief
      psychosocial intervention for alcoholism is available and appears to be feasible,
      safe and efficacious. 

PMID- 24918836
TI  - Ospemifene for the treatment of dyspareunia in postmenopausal women.
AB  - Ospemifene is a third-generation selective estrogen receptor modulator (SERM),
      structurally closely related to toremifene. Clinical studies in postmenopausal
      women with vulvovaginal atrophy demonstrated that it produced significant
      improvements in the structure of the vagina and its pH, and significantly reduced
      dyspareunia, the main complaint of the women treated. Preclinical studies
      demonstrated that ospemifene, unlike tamoxifen, did not produce DNA adducts,
      suggesting that it has less carcinogenic potential than tamoxifen. Preclinical
      and clinical studies showed that ospemifene has an agonist action on bone and
      reduced the growth of all breast cancer models in animal studies, providing they
      expressed estrogen receptor-alpha. Ospemifene had minimal effects on the
      endometrium of postmenopausal women. Ospemifene 60 mg once a day was approved by
      the U.S. Food and Drug Administration in February 2013 for women with moderate to
      severe dyspareunia. 

PMID- 24918837
TI  - Contemporary treatment options for relapsing-remitting multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system,
      encompassing both neuroinflammatory as well as prominent neurodegenerative
      aspects. A significant proportion of MS patients will develop neurological
      disability over time and up until recently licensed drugs could not
      satisfactorily halt this process. However, in the last years MS treatment has
      raised a stage of rapid progress. Several new drugs with significantly improved
      efficacy have entered the therapeutic field and several others are currently
      undergoing phase III clinical trials. In this review, we will summarize efficacy
      data as well as safety and tolerability issues of currently licensed drugs for
      relapsing-remitting MS and will give a short update on new drugs currently
      undergoing late-stage clinical trials. 

PMID- 24918838
TI  - A report from the 29th Annual Congress of the European Association of Urology
      (April 11-15 - Stockholm, Sweden).
AB  - The annual congress of the European Association of Urology in Stockholm was
      packed with mixed poster/oral sessions wherein innovative clinical and
      preclinical research aimed at improving the care of patients with urinary tract
      diseases was reported and open for discussion. Not everything that was reported
      during the meeting can be captured in a single report, but the following text
      will guide readers through the most significant new findings directly related
      with pharmacotherapy for overactive bladder, urinary tract cancer and other
      common medical conditions that endanger the quality of life and life expectancy
      of many patients worldwide. 

PMID- 24918839
TI  - Verbal learning in marijuana users seeking treatment: a comparison between
      depressed and non-depressed samples.
AB  - BACKGROUND: Both individuals with marijuana use and depressive disorders exhibit
      verbal learning and memory decrements. OBJECTIVES: This study investigated the
      interaction between marijuana dependence and depression on learning and memory
      performance. METHODS: The California Verbal Learning Test-Second Edition (CVLT
      II) was administered to depressed (n = 71) and non-depressed (n = 131) near-daily
      marijuana users. The severity of depressive symptoms was measured by the self
      rated Beck Depression Inventory (BDI-II) and the clinician-rated Hamilton
      Depression Rating Scale (HAM-D). Multivariate analyses of covariance statistics
      (MANCOVA) were employed to analyze group differences in cognitive performance.
      Pearson's correlation coefficients were calculated to examine the relative
      associations between marijuana use, depression and CVLT-II performance. Findings
      from each group were compared to published normative data. RESULTS: Although both
      groups exhibited decreased CVLT-II performance relative to the test's normative
      sample (p < 0.05), marijuana-dependent subjects with a depressive disorder did
      not perform differently than marijuana-dependent subjects without a depressive
      disorder (p > 0.05). Further, poorer CVLT-II performance was modestly associated
      with increased self-reported daily amount of marijuana use (corrected p < 0.002),
      but was not significantly associated with increased scores on measures of
      depressive symptoms (corrected p > 0.002). CONCLUSION: These findings suggest an
      inverse association between marijuana use and verbal learning function, but not
      between depression and verbal learning function in regular marijuana users.

PMID- 24918840
TI  - Differential Associations of Communication and Love in Heterosexual, Lesbian, and
      Bisexual Women's Perceptions and Experiences of Chronic Vulvar and Pelvic Pain.
AB  - The literature on genital and pelvic pain has largely focused on heterosexual
      women. An online study examined characteristics of vulvar pain in 839 lesbian,
      bisexual, and heterosexual women 18-45 years of age and investigated associations
      between relationship qualities such as love and communication with participants'
      perceptions of pain's influence on relationships. Characteristics of vulvar pain
      were similar across groups. Groups differed in how they perceived pain to impact
      their relationships, such that better communication for same-sex couples and more
      love for mixed-sex couples was associated with the perception of their pain as
      having less of an effect on their relationship functioning. 

PMID- 24918841
TI  - Nonlinear optical imaging of defects in cubic silicon carbide epilayers.
AB  - Silicon carbide is one of the most promising materials for power electronic
      devices capable of operating at extreme conditions. The widespread application of
      silicon carbide power devices is however limited by the presence of structural
      defects in silicon carbide epilayers. Our experiment demonstrates that optical
      second harmonic generation imaging represents a viable solution for
      characterizing structural defects such as stacking faults, dislocations and
      double positioning boundaries in cubic silicon carbide layers. X-ray diffraction
      and optical second harmonic rotational anisotropy were used to confirm the growth
      of the cubic polytype, atomic force microscopy was used to support the
      identification of silicon carbide defects based on their distinct shape, while
      second harmonic generation microscopy revealed the detailed structure of the
      defects. Our results show that this fast and noninvasive investigation method can
      identify defects which appear during the crystal growth and can be used to
      certify areas within the silicon carbide epilayer that have optimal quality. 

PMID- 24918842
TI  - Beyond the evidence: the values for the patient.

PMID- 24918843
TI  - A little more on the appearance of doctors.

PMID- 24918844
TI  - Update on chronic nonspecific lower back pain: rehabilitation.

PMID- 24918845
TI  - Vaccination in the prevention of infectious respiratory diseases in adults.

PMID- 24918846
TI  - Warfarin-induced gastric intramural hematoma.

PMID- 24918847
TI  - Breastfeeding exclusively and iron deficiency anemia during the first 6 months of
      age.
AB  - OBJECTIVE: The objective was to determine the prevalence of iron deficiency and
      iron deficiency anemia among exclusively breastfed infants from one to six months
      of life and to identify associated risk factors. METHODS: This is a cohort study
      of the hemoglobin and serum ferritin levels of 102 healthy full-term infants,
      weighing more than 2500 grams (5.5 pounds) at birth, evaluated for growth
      development and supported to promote exclusive breastfeeding. Hemoglobin and
      ferritin levels were measured in the first, fourth, and sixth months of life. The
      hemoglobin and ferritin levels of the mothers were also measured in the first
      month postpartum. RESULTS: At four months, 5.7% presented iron deficiency and
      3.4% had iron deficiency anemia. At six months, the percentage of children with
      iron deficiency increased more than four times, reaching 26.1%, while iron
      deficiency anemia was present in 23.9% of the infants studied. Iron deficiency at
      six months of age was significantly correlated to growth velocity. CONCLUSION:
      According to the results of this study, exclusive breastfeeding protects infants
      from iron deficiency and iron deficiency anemia for the first four months of
      life. After this age, in accordance with the literature, the findings of this
      study demonstrated an increase in anemia and iron deficiency rates, adding to
      evidence that supports the monitoring of iron levels in exclusively breastfed
      children presenting higher weight gains beginning at four months of age.

PMID- 24918848
TI  - Caffeine and physical training: effects on cardiac morphology and cardiovascular
      response.
AB  - OBJECTIVE: to analyze the morphological structure of cardiac, blood pressure
      (BP), heart rate (HR) and heart rate variability (HRV) of rats subjected to
      physical training with supplementation of caffeine. METHODS: 60 rats were divided
      into 4 groups: control (CO), control with caffeine (CAF), trained control (TRE)
      and trained with caffeine (TCAF). All trained groups underwent 4 weeks of
      swimming, and all caffeine groups were supplemented by voluntary ingestion of
      caffeine diluted in drinking water. RESULTS: there were no changes to BP and HR
      between groups. Regarding HRV, there was a decrease in LFnorm (low frequency) and
      LF/HF ratio (low and high frequency) in TCAF and CAF compared to group (p<0.02
      and p<0.03, respectively). An increase occurred in CAF compared to the CO in the
      component LFnorm (p<0.05). The results also showed an increase in the relative
      weight of heart in the TRE (p<0.04) and TCAF (p<0.03) compared to CO. CONCLUSION:
      caffeine did not modify the hemodynamic responses. However, physical training
      resulted in a decrease in sympathetic response and an increase in relative heart
      weight.

PMID- 24918849
TI  - Factors associated with treatment interruption for Hepatitis C.
AB  - OBJECTIVE: To evaluate risk factors related to Hepatitis C treatment
      interruption. METHODS: Retrospective cohort of patients seen at the Hepatology
      outpatient service at Hospital dos Servidores do Estado do Rio de Janeiro, from
      2001 to 2009. The factors investigated were: age, gender, genotype, degree of
      liver fibrosis, type of treatment, treatment time in weeks, diabetes mellitus,
      and systemic hypertension. Survival curves and bivariate and multivariate Cox
      regression models were used in the analyses. RESULTS: The risk of treatment
      interruption is six times greater in patients with more advanced degrees of liver
      fibrosis (F4) compared to those with less advanced degree (F2) in the period from
      0 to 24 weeks of treatment. Genotype was found to be an important factor to
      explain therapy cessation after 24 weeks of treatment - the risk of stopping
      treatment was 2.5 times higher in patients with genotype 3 than in those with
      genotype 1. CONCLUSION: Degree of liver fibrosis and genotype proved to be the
      main risk factors associated to treatment interruption.

PMID- 24918850
TI  - Interferon-induced depression in patients with hepatitis C: an epidemiologic
      study.
AB  - OBJECTIVE: To assess the incidence rate and severity of depressive symptoms in
      different time points (12, 24 and 48 weeks) in Brazilian patients with HCV
      treated with PEG IFN plus ribavirin. METHODS: We conducted an observational
      prospective study using the Beck Depression Inventory (BDI) and the Center for
      Epidemiologic Studies Depression Scale (CES-D). RESULTS: Fifty patients were
      included. The assessments with either scale showed the highest score of
      depressive symptoms in the 24(th) week of treatment; the mean BDI score before
      treatment was 6.5 +/- 5.3 and the mean CES-D was 10.9 +/- 7.8. After 24 weeks,
      the mean BDI was 16.1 +/- 10.2 and mean CES-D was 18.6 +/- 13.0; 46% were
      diagnosed with depression according to combined BDI and CES-D scores. The
      somatic/psychomotor subscales were highly correlated with overall scale scores .
      Subjects with history of substance and alcohol abuse had higher risk for IFN
      induced depression. CONCLUSION: Treatment with PEG IFN was associated with a high
      incidence rate of depressive symptoms in this sample of Brazilian patients, as
      measured by CES-D and BDI. Alcohol and substance abuse increase the risk of PEG
      IFN-induced depression.

PMID- 24918851
TI  - Is the anesthesiologist actually prepared for loss of airway or respiratory
      function? A cross-sectional study conducted in a tertiary hospital.
AB  - OBJECTIVE: To identify compliance with the procedures for securing the airway of
      patients submitted to anesthesia, defined as highly recommended in the World
      Health Organization Surgical Safety Checklist. METHODS: A prospective, cross
      sectional, observational study was conducted with 87 patients aged 18 to 60
      years, classified as ASA grade 1 or 2 according to the American Society of
      Anesthesiologists' Physical Status Classification. The study variables consisted
      of: whether the Mallampati test had been performed, whether equipment was readily
      available for orotracheal intubation, whether the correct placement of the
      endotracheal tube was verified, whether patient ventilation was monitored and
      whether fasting was confirmed. Prevalence ratios and their respective 95%
      confidence intervals were calculated as measures of relative risk. Statistical
      significance was defined at 5%. RESULTS: It was found that in 87.4% of patients,
      the airway was not evaluated using the Mallampati classification and in 51.7% of
      cases, preoperative fasting was not confirmed. In 29.9% of cases, the ready
      availability of equipment for orotracheal intubation was not verified. In all of
      the cases in which the availability of this equipment was not checked, the
      patient was submitted to regional anesthesia, with a statistically significant
      difference compared to the cases in which the patient was submitted to general
      anesthesia. CONCLUSION: Measures considered essential for the safety of the
      patient during surgery are still being ignored.

PMID- 24918852
TI  - Physical activity and sexual function in middle-aged women.
AB  - OBJECTIVE: To investigate the relationship between physical activity level and
      sexual function in middle-aged women. METHODS: A cross-sectional study with a
      sample of 370 middle-aged women (40-65 years old), treated at public health care
      facilities in a Brazilian city. A questionnaire was used containing enquiries on
      sociodemographic, clinical and behavioral characteristics: the International
      Physical Activity Questionnaire (IPAQ), short form, and the Female Sexual
      Function Index (FSFI). RESULTS: The average age of the women studied was 49.8
      years (+/- 8.1), 67% of whom exhibited sexual dysfunction (FSFI <= 26.55).
      Sedentary women had a higher prevalence (78.9%) of sexual dysfunction when
      compared to active (57.6%) and moderately active (66.7%) females (p = 0.002).
      Physically active women obtained higher score in all FSFI domains (desire,
      arousal, lubrication, orgasm, satisfaction and pain) and total FSFI score (20.9),
      indicating better sexual function than their moderately active (18.8) and
      sedentary (15.6) counterparts (p <0.05). CONCLUSION: Physical activity appears to
      influence sexual function positively in middle-aged women.

PMID- 24918853
TI  - Prevalence of low bone mineral density in adolescents and adults with cystic
      fibrosis.
AB  - OBJECTIVE: The aim of this cross-sectional study was to evaluate the prevalence
      of low bone mass density in cystic fibrosis patients as well as to evaluate the
      factors associated with bone mass in such patients. METHODS: Bone mass density
      was measured by dual-photon X-ray absorptiometry of lumbar spine (L1-L4), in
      patients <=19 years old, or lumbar spine and femur (total and neck) in patients
      >=20 years old. Evaluations of nutritional status, biochemical parameters, and
      lung function were performed. Medication data were obtained from medical records.
      RESULTS: Fifty-eight patients were included in the study (25 males/ 33 females),
      mean age 23.9 years (16-53 years). The prevalence of bone mass below the expected
      range for age at any site was 20.7%. None of the subjects had history of
      fracture. Lumbar spine Z-score in cystic fibrosis patients correlated positively
      with body mass index (r= 0.3, p=0.001), and forced expiratory volume in the first
      second (% predicted) (r=0.415, p=0.022). Mean lumbar spine Z-score was higher in
      women (p=0.001), in patients with no pancreatic insufficiency (p=0.032), and in
      patients with no hospitalization in the last 3 months (p=0.02). After
      multivariate analysis, body mass index (p= 0.001) and sex (p=0.001) were
      independently associated with Z-score in lumbar spine. CONCLUSION: Low bone mass
      is a frequent problem in patients with CF, being independently associated with
      body mass index, and male sex.

PMID- 24918854
TI  - Psychiatric comorbidity in diabetes type 1: a cross-sectional observational
      study.
AB  - OBJECTIVE: This study aims to investigate the prevalence of psychiatric
      disorders, i.e., the presence of signs and symptoms of anxiety and depression in
      type 1 diabetic patients, as well as to investigate the prevalence of psychiatric
      disorders in insulin dependent patients. METHODS: A cross-sectional observational
      study of 110 diabetic outpatients (mean = 58.3, SD = 14.5; 50 male and 60 female)
      was conducted in a public health clinic with patients diagnosed with diabetes
      mellitus who were under the medical supervision of an endocrinologist. The
      patients were evaluated through the Mini International Neuropsychiatric Interview
      and the Hospital Anxiety and Depression Scale(HADS). RESULTS: With respect to
      anxiety symptoms, we found a prevalence of 60% (n = 66) among patients, while in
      depression symptoms we found a prevalence of 53.6% (n = 59) concerning the 110
      patients evaluated. More specifically, we found 28.2% (n = 31) of patients
      without depression or anxiety, 13.6% (n = 15) of patients with depression, 16.4%
      (n = 18) of patients with anxiety and 41.8% (n = 46) of patients with depression
      combined with anxiety. The most remarkable data were generalized anxiety disorder
      (22.7%), dysthymia (18.2%), panic disorder (8.2%) and social phobia (5.5%).
      CONCLUSION: The need for accurate assessments about the presence of symptoms
      related to psychopathology in patients with type 1 diabetes is evident.

PMID- 24918855
TI  - Pre-hospital delay in acute myocardial infarction: judgement of symptoms and
      resistance to pain.
AB  - OBJECTIVE: To estimate the time of decision (TD) to look for medical care and the
      time of arrival (TA) at the health service for men (M) and women (W) suffering
      from acute myocardial infarction and to analyze the influence of the
      interpretation of pain and pain resistance behaviors during these times. METHODS:
      This is an exploratory research, performed at the university hospital in
      Salvador/Bahia. 43 W and 54 M were interviewed. To study the dependence among
      sociodemographic and gender variables, the Fisher Exact Test was used. To analyze
      times, a geometric mean (GM) was used. In order to verify the association between
      the GM of TD and TA and the judgment of pain, and between the GM of TD and TA and
      the behavior of resistance to pain, as well as to test the time of interaction
      between the gender variable and other variables of interest, the robust
      regression model was used. The statistical significance adopted was 5%. RESULTS:
      The GM of the TD for M was 1.13 h; for W, 0.74 h. The GM of the TA was 1.74 h for
      M and 1.47 h for W. Those who did not recognize the symptoms of AMI and presented
      behavior of resistance to pain had higher TD and TA, being the associations
      significant. Gender did not change the associations of interest. CONCLUSION: The
      findings demonstrate the importance of health education aiming at the benefits of
      early treatment.

PMID- 24918856
TI  - Sexual violence against children and vulnerability.
AB  - OBJECTIVE: To analyze the demographic and epidemiological profile of children and
      adolescents victims of sexual violence treated in a Unit of Forensic Medicine and
      the relationship between victims and perpetrators. METHODS: A descriptive study,
      with data collection from information gathered from sex abuse reports performed
      in 2009 on victims of sexual violence aged less than 18 years. The data
      collection tool was a form filled out with demographic information about the
      victim - gender and age - and information regarding the sexual violence -,
      location of the occurrence, time elapsed between abuse and expert report,
      complaints reported, sexological examination findings, description of lesions
      outside the genital region, and aggressor's relationship to victim. RESULTS: In
      2009, 421 individuals victim of sexual violence were assisted. Of those, 379
      (90%) were younger than 18 years, and 66 cases were excluded from these reports.
      Most were female (81.2%). The most affected age group was 10 to 13 years old
      (36.7%), followed by 5 to 9 year-olds (30.7%). In most cases (86.3%), there were
      family or friendship ties between victims and perpetrators, being most frequently
      accused an acquaintance or friend of the family (42.3%), followed by the
      stepfather (16.6%) and the father (10.9%). CONCLUSION: The results are similar to
      other studies conducted in the country. This work aims at filling a gap caused by
      the lack of research on this topic in the State, hoping to collaborate to improve
      public policies against child sexual abuse.

PMID- 24918857
TI  - Association between oxidative stress and nutritional status in the elderly.
AB  - Ageing is a dynamic and progressive process that is characterized by the
      occurrence of morphological, biochemical, functional and psychological changes in
      the organism. The aim of the present article is to provide updated concepts on
      oxidative stress, covering its importance in aging, as well as nutritional status
      and supplementation with antioxidants (substances that prevent or attenuate
      oxidation of oxidizable substrates, such as lipids, proteins, carbohydrates and
      deoxyribonucleic acid) in the geriatric population. Evidence suggests that there
      is an inverse relationship between oxidative stress and nutritional status in
      elderly individuals. Although an increase in oxidative stress in chronic diseases
      associated with aging has been proven, such as Parkinson's disease and
      Alzheimer's disease, up to now there has been no consistent clinical evidence
      proving the efficiency of supplementation with antioxidants against oxidative
      stress. In this context, supplementation is not recommended. On the other hand,
      the elderly should be encouraged to eat antioxidant foods, such as fruits and
      vegetables. Maintaining a normal weight (body mass index between 23 and 28
      Kg/m(2)) should also be stimulated.

PMID- 24918858
TI  - Cortisol: the villain in metabolic syndrome?
AB  - OBJECTIVE: This article reviews the state of the art regarding the association
      between glucocorticoid actions and both obesity and insulin resistance, two main
      features of the metabolic syndrome. METHODS: A methodological assessment of the
      literature on PubMed and SciELO databases was conducted by using the following
      terms: stress, metabolic syndrome, glucocorticoids, obesity, insulin resistance,
      hypothalamic-pituitary-adrenal-axis and 11beta-hydroxysteroid dehydrogenase.
      RESULTS: Chronic stress, mainly through hypothalamic-pituitary-adrenal axis
      dysregulation, promotes the accumulation of visceral fat. Reciprocally, obesity
      promotes a systemic low-grade inflammation state, mediated by increased adipokine
      secretion, which can chronically stimulate and disturb stress system. This
      vicious cycle, probably initiated by visceral adipose tissue dysfunction, might
      be the trigger for the development of metabolic syndrome. CONCLUSION: Given the
      strong evidences linking glucocorticoid release, obesity and type 2 diabetes,
      better understanding of the mechanisms underlying this connection might be useful
      for prevention and treatment of the metabolic syndrome.

PMID- 24918859
TI  - What explains usage of mobile physician-rating apps? Results from a web-based
      questionnaire.
AB  - BACKGROUND: Consumers are increasingly accessing health-related information via
      mobile devices. Recently, several apps to rate and locate physicians have been
      released in the United States and Germany. However, knowledge about what kinds of
      variables explain usage of mobile physician-rating apps is still lacking.
      OBJECTIVE: This study analyzes factors influencing the adoption of and
      willingness to pay for mobile physician-rating apps. A structural equation model
      was developed based on the Technology Acceptance Model and the literature on
      health-related information searches and usage of mobile apps. Relationships in
      the model were analyzed for moderating effects of physician-rating website (PRW)
      usage. METHODS: A total of 1006 randomly selected German patients who had visited
      a general practitioner at least once in the 3 months before the beginning of the
      survey were randomly selected and surveyed. A total of 958 usable questionnaires
      were analyzed by partial least squares path modeling and moderator analyses.
      RESULTS: The suggested model yielded a high model fit. We found that perceived
      ease of use (PEOU) of the Internet to gain health-related information, the
      sociodemographic variables age and gender, and the psychographic variables
      digital literacy, feelings about the Internet and other Web-based applications in
      general, patients' value of health-related knowledgeability, as well as the
      information-seeking behavior variables regarding the amount of daily private
      Internet use for health-related information, frequency of using apps for health
      related information in the past, and attitude toward PRWs significantly affected
      the adoption of mobile physician-rating apps. The sociodemographic variable age,
      but not gender, and the psychographic variables feelings about the Internet and
      other Web-based applications in general and patients' value of health-related
      knowledgeability, but not digital literacy, were significant predictors of
      willingness to pay. Frequency of using apps for health-related information in the
      past and attitude toward PRWs, but not the amount of daily Internet use for
      health-related information, were significant predictors of willingness to pay.
      The perceived usefulness of the Internet to gain health-related information and
      the amount of daily Internet use in general did not have any significant effect
      on both of the endogenous variables. The moderation analysis with the group
      comparisons for users and nonusers of PRWs revealed that the attitude toward PRWs
      had significantly more impact on the adoption and willingness to pay for mobile
      physician-rating apps in the nonuser group. CONCLUSIONS: Important variables that
      contribute to the adoption of a mobile physician-rating app and the willingness
      to pay for it were identified. The results of this study are important for
      researchers because they can provide important insights about the variables that
      influence the acceptance of apps that allow for ratings of physicians. They are
      also useful for creators of mobile physician-rating apps because they can help
      tailor mobile physician-rating apps to the consumers' characteristics and needs.

PMID- 24918862
TI  - Octahedral to trigonal prismatic distortion driven by subjacent orbital pi
      antibonding interactions and modulated by ligand redox noninnocence.
AB  - Ru(ONO)2 and Os(ONO)2 distort from octahedral towards trigonal prismatic geometry
      in order to relieve pi antibonding due to donation from the second-highest ligand
      orbital to the metal. Increasing oxidation of the ONO ligand suppresses
      distortion by increasing sigma* interactions in the trigonal prism. 

PMID- 24918863
TI  - Optimization of subcritical water extraction of flavanols from green tea leaves.
AB  - The subcritical-water extraction (SWE) of six kinds of flavanols from green tea
      leaves and the effect of extraction conditions were investigated by varying the
      temperature and time. The maximum yield of total flavanols, 71.36 +/- 4.23 mg/g
      green tea leaves (mean +/- SD), was obtained under extraction temperature/time
      conditions of 150  degrees C/5 min. The efficiency of SWE for total flavanols was
      slightly higher than that of the conventional extraction solvents such as
      methanol and ethanol. The extraction of flavanols via SWE was specifically
      adequate for epimer structures such as catechin, catechin gallate, and
      gallocatechin gallate due to the epimerization of epicatechins. The extraction
      efficiency of epimers was increased at temperatures up to 170  degrees C, whereas
      that of epicatechins was decreased. Thus, most epicatechins were converted to
      epimers during SWE, leading to some flavanol destruction at high temperatures,
      except when a short extraction time of 5 min was used. 

PMID- 24918864
TI  - Highly regio- and stereoselective synthesis of alkylidenecyclopropanes via Ru(II)
      Pheox catalyzed asymmetric inter- and intramolecular cyclopropanation of allenes.
AB  - An efficient protocol for the synthesis of optically active
      alkylidenecyclopropanes (ACPs) via the Ru(II)-Pheox catalyzed asymmetric
      cyclopropanation of allenes has been established. This catalytic system proceeded
      with high regioselectivity to give the ACP products in high yield with high
      diastereoselectivity (up to 99/1) and enantioselectivity (up to 99% ee). 

PMID- 24918865
TI  - Ultrafast and wide range analysis of DNA molecules using rigid network structure
      of solid nanowires.
AB  - Analyzing sizes of DNA via electrophoresis using a gel has played an important
      role in the recent, rapid progress of biology and biotechnology. Although
      analyzing DNA over a wide range of sizes in a short time is desired, no existing
      electrophoresis methods have been able to fully satisfy these two requirements.
      Here we propose a novel method using a rigid 3D network structure composed of
      solid nanowires within a microchannel. This rigid network structure enables
      analysis of DNA under applied DC electric fields for a large DNA size range (100
      bp-166 kbp) within 13 s, which are much wider and faster conditions than those of
      any existing methods. The network density is readily varied for the targeted DNA
      size range by tailoring the number of cycles of the nanowire growth only at the
      desired spatial position within the microchannel. The rigid dense 3D network
      structure with spatial density control plays an important role in determining the
      capability for analyzing DNA. Since the present method allows the spatial
      location and density of the nanostructure within the microchannels to be defined,
      this unique controllability offers a new strategy to develop an analytical method
      not only for DNA but also for other biological molecules.

PMID- 24918866
TI  - The efficacy of neoadjuvant chemotherapy in different histological types of
      cervical cancer.
AB  - OBJECTIVE: To determine whether the efficacy of neoadjuvant chemotherapy (NACT)
      is different among cervical cancer types, squamous cell carcinoma (SCC) and non
      SCC, including adenocarcinoma of the cervix (ACC) and adenosquamous carcinoma
      (ASC). METHODS: We searched PubMed, MEDLINE, ScienceDirect, Springerlink and CNKI
      for studies published between Jan 1987 and Sep 2012 and evaluated the studies
      published in English and Chinese on NACT and cervical carcinoma based on specific
      inclusion and exclusion criteria. Because there was a relative lack of relevant
      randomized controlled trials (RCTs), we included 2 RCTs and 9 observational
      studies in our analysis. Meta-analysis was applied to calculate the efficacy of
      NACT in different histological types of cervical cancer with 95% confidence
      intervals. The risk of bias was assessed by Begg's adjusted rank correlation test
      and Egger's regression asymmetry tests. RESULTS: As many as 11 articles, 2 RCTs
      and 9 observational studies, were selected according to the eligibility criteria
      for a total of 1559 participants. For the short-term efficacy of NACT, either in
      terms of CR+PR or CR only, there was no difference between SCC and non-SCC when
      the data were pooled (P>0.05) in stratified studies based on the International
      Federation of Gynecology and Obstetrics (FIGO) stage (P>0.05) or histological
      type (P>0.05) or in observational studies (P>0.05). Nevertheless, SCC was
      associated with a higher short-term response rate than non-SCC in RCTs [6.57
      (95%CI 1.72-25.12) in CR+PR]. For the long-term outcome of NACT, patients with
      SCC experienced a significant 5-year overall survival (OS) and progress-free
      survival (PFS) when compared to patients with non-SCC in pooled [1.47 (95%CI 1.06
      2.06)] and observational studies [1.96 (95%CI 1.61-2.38)] other than RCTs
      (P>0.05). Moreover, this difference was especially obvious when the subgroup
      analysis was restricted to patients in stages above IIB [2.06 (95%CI 1.79-2.36)]
      rather than in stages IB-IIB [1.33 (95%CI 0.99-1.79)]. CONCLUSION: Although no
      significant differences exist in the short-term efficacy of NACT, the
      histological type may be used to predict the long-term efficacy of NACT in
      patients with cervical cancer, especially those with FIGO stages above IIB.

PMID- 24918868
TI  - [Development of a claim form for the initiation of post-treatment rehabilitation
      for nationwide use by all reimbursement agencies: a report and plea for reducing
      administrative barriers].
AB  - We describe the results of a survey of claim forms that are used when starting
      rehabilitation following inpatient treatment and of an evaluation of a claim form
      developed on the basis of the results. The survey of different existing forms
      shows a high overlapping in content, suggesting the possibility of unification to
      one claim form that can be accepted by all insurers. In analogy to the Delphi
      method criteria for evaluation were consented and applied by the author group to
      assess the relevance of the claim forms content items for the process of
      initiating rehabilitation. A group of further experts added their evaluations. We
      prioritised the results and extracted the essential contents to conceive a
      unified claim form eligible for all types of rehabilitation. The claim form was
      discussed in 3 focus groups, revised accordingly and tested in the Hannover
      Medical School. Test results show that all relevant information is asked for and
      that the form is well manageable. The users' request for an IT-based solution and
      further ideas for improvement were integrated into the revised and validated
      version of the claim form. It is now available for all stake holders, in
      particular for insurers, as a means to improve quality of care and efficiency by
      standardisation of rehabilitation claim forms.

PMID- 24918869
TI  - [Health inequalities and cost-effectiveness: what do important health policy
      actors say about this potential conflict situation?].
AB  - The German statutory health-care system is based on the principle of solidarity
      and thus it is committed to the objective of 'equal chances'. From an economic
      perspective it is also important to emphasise that scarcity of resources
      continuously pushes the services towards cost control and towards increasing cost
      effect-iveness. There could be conflicts between the 2 objectives 'equal chances'
      and 'cost-effectiveness', of course, for example if measures for increasing cost
      effectiveness lead to increased financial burdens of the insured. To date it has
      not been studied if and how this potential conflict is discussed in Germany.In a
      first step we searched for German publications discussing this potential conflict
      focusing on 3 major public health journals (Das Gesundheitswesen,
      Bundesgesundheitsblatt, Ethik in der Medizin) and on the internet portal
      "gerechte-gesundheit.de". For the main part of the paper, we looked for
      publications from 4 major health policy actors (Bundesarztekammer, Zentrale
      Ethikkommission bei der Bundesarztekammer, Deutscher Ethikrat,
      Sachverstandigenrat zur Begutachtung der Entwicklung im Gesundheitswesen). All
      papers published since the year 2000 were included in the system-atic qualitative
      analysis.The analyses show that the potential conflict between 'equal chances'
      and 'cost-effectiveness' is rarely discussed in any detail, at most in an
      implicit way. It would be important, though, to have an explicit discussion,
      supported by scientifically based analyses and recommendations. One step towards
      this objective could be, for example, a closer cooperation between social
      epidemiologists and health--economists. 

PMID- 24918867
TI  - Antimicrobial peptides in reptiles.
AB  - Reptiles are among the oldest known amniotes and are highly diverse in their
      morphology and ecological niches. These animals have an evolutionarily ancient
      innate-immune system that is of great interest to scientists trying to identify
      new and useful antimicrobial peptides. Significant work in the last decade in the
      fields of biochemistry, proteomics and genomics has begun to reveal the
      complexity of reptilian antimicrobial peptides. Here, the current knowledge about
      antimicrobial peptides in reptiles is reviewed, with specific examples in each of
      the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras),
      Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are
      presented of the major classes of antimicrobial peptides expressed by reptiles
      including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP
      2), lysozyme, crotamine, and others. Some of these peptides have been identified
      and tested for their antibacterial or antiviral activity; others are only
      predicted as possible genes from genomic sequencing. Bioinformatic analysis of
      the reptile genomes is presented, revealing many predicted candidate
      antimicrobial peptides genes across this diverse class. The study of how these
      ancient creatures use antimicrobial peptides within their innate immune systems
      may reveal new understandings of our mammalian innate immune system and may also
      provide new and powerful antimicrobial peptides as scaffolds for potential
      therapeutic development. 

PMID- 24918870
TI  - Property- and structure-guided discovery of a tetrahydroindazole series of
      interleukin-2 inducible T-cell kinase inhibitors.
AB  - Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of
      tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell
      receptor (TCR), and considerable efforts have been directed toward discovery of
      ITK-selective inhibitors as potential treatments of inflammatory disorders such
      as asthma. Using a previously disclosed indazole series of inhibitors as a
      starting point, and using X-ray crystallography and solubility forecast index
      (SFI) as guides, we evolved a series of tetrahydroindazole inhibitors with
      improved potency, selectivity, and pharmaceutical properties. Highlights include
      identification of a selectivity pocket above the ligand plane, and identification
      of appropriate lipophilic substituents to occupy this space. This effort
      culminated in identification of a potent and selective ITK inhibitor (GNE-9822)
      with good ADME properties in preclinical species. 

PMID- 24918872
TI  - Highly exothermic and superhydrophobic Mg/fluorocarbon core/shell nanoenergetic
      arrays.
AB  - Mg/fluorocarbon core/shell nanoenergetic arrays are prepared onto silicon
      substrate, with Mg nanorods as the core and fluorocarbon as the shell. Mg
      nanorods are deposited by the glancing angle deposition technique, and the
      fluorocarbon layer is then prepared as a shell to encase the Mg nanorods by the
      magnetron sputtering deposition process. Scanning electron microscopy and
      transmission electron microscopy show the core/shell structure of the
      Mg/fluorocarbon arrays. X-ray energy-dispersive spectroscopy, X-ray diffraction,
      and Fourier transform infrared spectroscopy are used to characterize the
      structural composition of the Mg/fluorocarbon. It is found that the as-prepared
      fluorocarbon layer consists of shorter molecular chains compared to that of bulk
      polytetrafluoroethylene, which is proven beneficial to the low onset reaction
      temperature of Mg/fluorocarbon. Water contact angle test demonstrates the
      superhydrophobicity of the Mg/fluorocarbon arrays, and a static contact angle as
      high as 162 degrees  is achieved. Thermal analysis shows that the Mg/fluorocarbon
      material exhibits a very low onset reaction temperature of about 270  degrees C
      as well as an ultrahigh heat of reaction approaching 9 kJ/g. A preliminary
      combustion test reveals rapid combustion wave propagation, and a convective
      mechanism is adopted to explain the combustion behaviors. 

PMID- 24918871
TI  - Ultrasound-accelerated, catheter-directed thrombolysis for inferior vena cava
      thrombosis after an orthotopic liver transplant.
AB  - Inferior vena cava thrombosis is a rare occurrence after an orthotopic liver
      transplant that is associated with a high rate of retransplant and mortality.
      There is no consensus regarding the optimal therapeutic strategy. Surgical
      management, including thrombectomy with revision of the cavocaval anastomosis,
      has been described. With the use of endovascular therapies, several minimally
      invasive approaches are available that are effective and avoid the high morbidity
      associated with reoperative surgery. We describe our successful experience using
      an approach after a liver transplant in which the inferior vena cava thrombosis
      in a patient presenting with acute renal failure, anorexia, weight loss, and
      fatigue using an ultrasound-accelerated, catheter-directed thrombolysis platform
      in conjunction with systemic anticoagulation. 

PMID- 24918873
TI  - Chemical disinfection of combined sewer overflow waters using performic acid or
      peracetic acids.
AB  - We investigated the possibility of applying performic acid (PFA) and peracetic
      acid (PAA) for disinfection of combined sewer overflow (CSO) in existing CSO
      management infrastructures. The disinfection power of PFA and PAA towards
      Escherichia coli (E. coli) and Enterococcus was studied in batch-scale and pre
      field experiments. In the batch-scale experiment, 2.5 mg L(-1) PAA removed
      approximately 4 log unit of E. coli and Enterococcus from CSO with a 360 min
      contact time. The removal of E. coli and Enterococcus from CSO was always around
      or above 3 log units using 2-4 mg L(-1) PFA; with a 20 min contact time in both
      batch-scale and pre-field experiments. There was no toxicological effect measured
      by Vibrio fischeri when CSO was disinfected with PFA; a slight toxic effect was
      observed on CSO disinfected with PAA. When the design for PFA based disinfection
      was applied to CSO collected from an authentic event, the disinfection
      efficiencies were confirmed and degradation rates were slightly higher than
      predicted in simulated CSO.

PMID- 24918874
TI  - Likelihood-Based Random-Effect Meta-Analysis of Binary Events.
AB  - Meta-analysis has been used extensively for evaluation of efficacy and safety of
      medical interventions. Its advantages and utilities are well known. However,
      recent studies have raised questions about the accuracy of the commonly used
      moment-based meta-analytic methods in general and for rare binary outcomes in
      particular. The issue is further complicated for studies with heterogeneous
      effect sizes. Likelihood-based mixed-effects modeling provides an alternative to
      moment-based methods such as inverse-variance weighted fixed- and random-effects
      estimators. In this article, we compare and contrast different mixed-effect
      modeling strategies in the context of meta-analysis. Their performance in
      estimation and testing of overall effect and heterogeneity are evaluated when
      combining results from studies with a binary outcome. Models that allow
      heterogeneity in both baseline rate and treatment effect across studies have low
      type I and type II error rates, and their estimates are the least biased among
      the models considered. 

PMID- 24918875
TI  - Modified Multivisceral Transplant After Acute Abdominal Trauma.
AB  - A 50-year-old man sustained blunt abdominal trauma in a motor vehicle accident.
      He underwent exploratory laparotomy on the day of trauma, and severe bleeding
      from the base of the small bowel mesentery was controlled by mass ligation and
      through-and-through suturing. After transfer to our center, repeat exploratory
      laparotomy showed ischemic small intestine, ischemic right colon, and severe
      pancreatic trauma. The severely injured organs were excised including the entire
      small bowel, pancreas, spleen, stomach, and right hemicolon. The next day, a
      modified multivisceral transplant was performed including stomach,
      pancreaticoduodenal complex, and small bowel transplant. Postoperative
      complications included an intra-abdominal collection that was drained
      percutaneously with ultrasonographic guidance and severe rejection that was
      treated with anti-thymocyte globulin. In summary, for select patients who have
      severe abdominal trauma may be treated with acute multivisceral transplant. 

PMID- 24918876
TI  - Innovation and responsibility in education and research in Latin America.

PMID- 24918877
TI  - [Intimate partner violence against pregnant women: study about the repercussions
      on the obstetric and neonatal results].
AB  - This observational, descriptive and analytic study aimed to identify the
      prevalence of IPV cases among pregnant women and classify them according to the
      type and frequency; identify the obstetric and neonatal results and their
      associations with the intimate partner violence (IPV) occurrence in the current
      pregnancy. It was developed with 232 pregnant women who had prenatal care at a
      public maternity hospital. Data were collected via structured interview and in
      the patients' charts and analyzed through the statistic software SAS(r) 9.0.
      Among the participants, 15.5% suffered IPV during pregnancy, among that 14.7%
      suffered psychological violence, 5.2% physical violence and 0.4% sexual violence.
      Women who did not desire the pregnancy had more chances of suffering IPV (p<0.00;
      OR=4.32 and 95% CI [1.77 - 10.54]). With regards to the obstetric and neonatal
      repercussions, there was no statistical association between the variables
      investigated. Thus, for the study participants there were no negative obstetric
      and neonatal repercussions related to IPV during pregnancy. 

PMID- 24918878
TI  - [Social representations of violence against rural women: unveiling senses in
      multiple views].
AB  - We analyze the social representations of violence against women from the
      perspective of city managers, professionals and health workers in rural settings
      of the southern half of Rio Grande do Sul. The study has a qualitative approach
      and adds a theoretical/methodological perspective of social representations. The
      data were generated by means of the associative method, question-stimulus of
      words and expressions emergence. The analysis of word association was performed
      with EVOC software, considering frequency and order of association with inducing
      terms. Participants recognize violence against women as gender destination that
      induces consent, resignation, guilt and fear, and results in naturalization and
      trivialization of this social phenomenon. We highlight the need to produce
      ruptures in established and traditional forms of health care, in the conservative
      and stereotypical views of violence, favoring access to friendly service and
      avoiding the reproduction of gender inequalities. 

PMID- 24918879
TI  - [Ankle-brachial index: nurses strategy to cardiovascular disease risk factors
      identification].
AB  - Elevated risk of fatal and non-fatal cardiovascular events is associated with
      high prevalence of peripheral arterial disease, with assessment through the ankle
      brachial index (ABI). This study aimed to demonstrate that the ABI and the
      Edinburgh Claudication Questionnaire are tools to be used by nurses in prevention
      and/or treatment of CVD (cardiovascular disease). A cross-sectional study was
      carried out with patients from a cardiovascular clinic. The Edinburgh
      Claudication Questionnaire was applied and the ABI was measured with the formula
      (ABI= Blood Pressure Ankle/Blood Pressure Brachial). A total of 115 patients were
      included, most were females (57.4%), aged 60.6 +/- 12.5 years. The most prevalent
      risk factors were hypertension (64.3%), physical inactivity (48.7%) and family
      history (58.3%). The study showed that abnormal ABI was frequently found and
      42.6% of the patients with abnormal ABI showed intermittent claudication. The
      method to evaluate the ABI associated to the Edinburg Claudication Questionnaire,
      can be easily used by nurses in the clinical evaluation of asymptomatic and
      symptomatic CVD patients. 

PMID- 24918880
TI  - [Hypothermia prevention during surgery: comparison between thermal mattress and
      thermal blanket].
AB  - This study aimed to compare the efficiency of the thermal blanket and thermal
      mattress in the prevention of hypothermia during surgery. Thirty-eight randomized
      patients were divided into two groups (G1 - thermal blanket and G2 - thermal
      mattress). The variables studied were: length of surgery, length of stay in the
      post-anesthetic care unit, period without using the device after thermal
      induction, transport time from the operating room to post-anesthetic care unit,
      intraoperative fluid infusion, surgery size, anesthetic technique, age, body mass
      index, esophageal, axillary and operating room temperature. In G2, length of
      surgery and starch infusion longer was higher (both p=0.03), but no hypothermia
      occurred. During the surgical anesthetic procedure, the axillary temperature was
      higher at 120 minutes (p=0.04), and esophageal temperature was higher at 120
      (p=0.002) and 180 minutes (p=0.03) and at the end of the procedure (p=0.002). The
      thermal mattress was more effective in preventing hypothermia during surgery. 

PMID- 24918881
TI  - [Overweight and obesity repercussion in the postoperative of myocardial
      revascularization surgery].
AB  - This is a descriptive, retrospective study with cross-sectional quantitative
      approach, which aimed to relate the body mass index with events in the
      postoperative period of the myocardial revascularization surgery with use of
      extracorporeal circulation. The data collection period was between April and
      June/2012. Patients were divided according to the body mass index and classified
      as without excess of weight, overweight or obese. The data analysis was based on
      the descriptive statistics. The patients without excess of weight had more
      complications, especially those related to the lungs. Among overweight and obese
      individuals, the cardiovascular complications stood out. The obese subjects had
      the worse prognostic. Obesity and overweight did not have statistically
      significant association with a higher frequency of postoperative complications,
      in spite of the occurrence of cardiovascular complications in this group. The
      patients without excess of weight had higher risks of developing neurological
      events. 

PMID- 24918883
TI  - [Cross mapping of nursing diagnoses in infant health using the international
      classification of nursing practice].
AB  - This was a descriptive, retrospective study, with a quantitative method, with the
      aim of analyzing the nursing diagnoses contained in the records of children of 0
      to 36 months of age who attended infant health nursing consults. A documentary
      analysis and the cross-mapping technique were used. One hundred eighty-eight
      different nursing diagnoses were encountered, of which 33 (58.9%) corresponded to
      diagnoses contained in the Nomenclature of Nursing Diagnoses and Interventions
      and 23 (41.1%) were derived from ICNP(r) Version 1.0. Of the 56 nursing
      diagnoses, 43 (76.8%) were considered to be deviations from normalcy. It was
      concluded that the infant health nursing consults enabled the identification of
      situations of normalcy and abnormality, with an emphasis on the diagnoses of
      deviations from normalcy. Standardized language favors nursing documentation,
      contributing to the care of the patient and facilitating communication between
      nurses and other health professionals. 

PMID- 24918882
TI  - [Insomnia symptoms, daytime naps and physical leisure activities in the elderly:
      FIBRA Study Campinas].
AB  - The practice of physical activities contributes to reducing the risk of chronic
      diseases and improves sleep patterns in the elderly. This research aimed to
      investigate the association between insomnia symptoms and daytime nap and the
      participation in physical leisure activities in elderly community residents. Data
      from the Studies Network of the Fragility in Brazilian Elderly (Campinas site),
      were used. Information from 689 elderly was analyzed, regarding sociodemographic
      characterization, physical leisure activity, occurrence of daytime napping and
      its duration, symptoms of insomnia and use of sleep medication. A significant
      association was found between the practice of walking and the daytime nap of
      short duration. Studies indicate that a short nap can benefit the quality of
      sleep and health of the elderly. Therefore, promoting the practice of walking can
      be a nursing intervention that favors the sleep patterns of the elderly. 

PMID- 24918884
TI  - [Adherence to diabetes mellitus treatments in family health strategy units].
AB  - This cross-sectional study aimed to analyze the adherence to drug and non-drug
      treatments in 17 Family Health Strategy units. A total of 423 patients with type
      2 diabetes mellitus were selected through stratified random sampling in Family
      Health Strategy units of a city in the state of Minas Gerais, Brazil, in 2010.
      The results showed that the prevalence rate of adherence to drug therapy was
      higher than 60% in the 17 units investigated; in relation to physical activity,
      adherence was higher than 60% in 58.8% units; and for the diet plan, there was no
      adherence in 52.9% units. Therefore, we concluded that adherence to drug therapy
      in most units was high and the practice of physical activity was heterogeneous,
      and in relation to diet adherence, it was low in all units. We recommend
      strengthening of institutional guidelines and educational strategies, in line
      with SUS guidelines, so that, professionals may face the challenges imposed by
      the lack of adherence. 

PMID- 24918885
TI  - [Pressure ulcers in palliative home care patients: prevalence and
      characteristics].
AB  - Persons in palliative care develop pressure ulcers (PU) as death approaches, but
      the extent of the problem is still unknown. The objectives were to identify the
      prevalence of pressure ulcers in people with cancer in palliative home care,
      compare the socio-demographic and clinical profile of patients with and without
      pressure ulcers, and analyze the characteristics of the ulcers. This descriptive,
      cross-sectional study included 64 people with advanced cancer in palliative home
      care. Twelve of them (18.8%) had PU, of whom 75.0% were men. The participants had
      one to three PU, amounting to 19 lesions, 89.4% of those developed at home and
      47.4% at stage 3. The presence of PU was higher among those who had a history of
      previous wound. PU consisted of a significant event occurring in the studied
      population, indicating that preventive measures should be included in the home
      palliative care health team. 

PMID- 24918886
TI  - [Nephrotoxicity of polymyxin B: experimental study in cells and implications for
      nursing practice].
AB  - The aim of the study was to characterize the cell damage mechanisms involved in
      the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC
      - PK1) and discuss about the nurses interventions to identify at risk patients
      and consider prevention or treatment of nephrotoxicity acute kidney injury. This
      is a quantitative experimental in vitro study, in which the cells were exposed to
      375MUM polymyxin B sulfate concentration. Cell viability was determined by
      exclusion of fluorescent dyes and morphological method with visualization of
      apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed
      reduced viability, increased number of apoptotic cells and a higher concentration
      of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro
      showed the need for actions to minimize adverse effects such as nephrotoxicity. 

PMID- 24918887
TI  - Cancer patients caregivers comfort.
AB  - Cross-sectional study, carried out at the outpatient clinic of an oncology
      hospital. Data were collected from 88 caregivers of cancer patients using the
      Caregiver General Comfort Questionnaire (GCQ) to assess the caregivers' comfort.
      The caregivers' GCQ score mean was 203.9; better comfort scores was associated
      with age, care time and current occupation; positive aspects of comfort were
      related to the fact that caregivers felt loved, to patients' physical and
      environmental comfort and to caregivers' spirituality. 203.9; better comfort
      scores were associated with age of the caregiver and current occupation; positive
      aspects of comfort were related to the fact that caregivers felt loved, to
      patients' physical and environmental comfort and to caregivers' spirituality.
      Caregivers, who didn't have a paid job or leisure's activities showed a worse
      GCQ. The GCQ scale can help to identify factors that interfere in caregivers'
      comfort, as well as needs that can be modified through health professionals'
      interventions. 

PMID- 24918888
TI  - [Virtual guide on ocular self-examination to support the self-care practice for
      people with HIV/AIDS].
AB  - The objective was to describe the process of development of a virtual guide on
      ocular self-examination for people with HIV/aids. The methodological proposal
      followed the five steps recommended by Falkembach: analysis and planning,
      modeling, implementation, evaluation and distribution. The adequacy of the
      printed version to the virtual required the construction of a tutorial video,
      adding illustrative photos for viewing possible ocular changes and interactive
      tool demonstrating the examination result to the user. In the first material
      assessment, we diagnosed failures in the layout, thus commands were replaced,
      unified, rearranged in an easy viewing and adequacy of language. It is possible
      to promote the approximation of users with prevention methods in the ocular
      health area through a virtual guide, contributing to develop skills and
      disseminate self-examination.

PMID- 24918889
TI  - [Communication strategies of the nursing team in the aphasia after
      cerebrovascular accident].
AB  - This is an exploratory, cross-sectional study of quantitative design that aimed
      to identify the communication strategies used and reported by the nursing staff
      in the care of aphasic patients after a stroke. The techniques used were the
      participant observation and interviews with 27 subjects of the nursing staff of
      neurological units in a general hospital. The most frequently mentioned
      strategies were gestures (100%), verbal communication (33.3%), written
      communication (29.6%) and the touch (18.5 %). Among the observed strategies, the
      gestures reached 40.7% and the touch was present in all situations, given its
      instrumental character essential to care. The findings show lack of knowledge of
      nonverbal, proxemics , kinesics and tacesics communication. No significant
      differences were observed among the professional categories depending on the
      length of experience with respect to the strategies reported by members of the
      nursing staff in the care for aphasic patients. 

PMID- 24918890
TI  - Addressing practical issues related to nursing care for international visitors to
      Hiroshima.
AB  - When nine million foreigners visited Japan in 2013, the federal government set a
      goal to attract an additional two and a half million visitors including medical
      tourists by 2020. This research investigates the attitudes and concerns of
      Japanese nurses when they are in a situation dealing with foreign patients. The
      data were collected from March through September 2010, from 114 nurses at three
      hospitals, in close proximity to popular tourist destinations in Hiroshima. A
      questionnaire was developed for this research, named Mari Meter, which included a
      section to write answers to an open question for the nurses to express their
      opinions. These responses were examined statistically and by word analysis using
      Text Mining Studio. Japanese nurses expressed greatest concern about payment
      options, foreign language skills, and issues of informed consent, when dealing
      with foreigners. The results confirm that, in order to provide a high quality of
      patient care, extra preparation and a greater knowledge of international workers
      and visitors are required by nursing professionals in Japan. 

PMID- 24918891
TI  - [The organizational culture of a Brazilian public hospital].
AB  - The objective of this research was to analyze the organizational culture of a
      Brazilian public hospital. It is a descriptive study with quantitative approach
      of data, developed in a public hospital of Sao Paulo State, Brazil. The sample
      was composed by 52 nurses and 146 nursing technicians and auxiliaries. Data were
      collected from January to June 2011 using the Brazilian Instrument for Assessing
      Organizational Culture - IBACO. The analysis of the organizational values showed
      the existence of hierarchical rigidity and centralization of power within the
      institution, as well as individualism and competition, which hinders teamwork.
      The values concerning workers' well-being, satisfaction and motivation were not
      highly valued. In regard to organizational practices, the promotion of
      interpersonal relationship, continuous education, and rewarding practices were
      not valued either. It becomes apparent that traditional models of work
      organization support work practices and determine the organizational culture of
      the hospital.

PMID- 24918892
TI  - [Improvement courses about violence prevention: the impact on health sector
      professionals].
AB  - Uncontrolled intervention study that compared the effectiveness of two elective
      courses on Prevention and Assistance to violence victims for students and
      professionals of the Health Sector. The participants answered multiple-choice
      questions on the topic before and after the course. Statistical analyzes were
      performed by comparison of two proportions on STATA/IC. Regarding the overall
      index of correct answers,before and after, it was 54.8 and 58.4% in the 10h
      Course and the 69.6 and 79.2% in the 30h Course. The most effective course was
      the 30h Course, with strategies of case discussions and visits to assistance
      services to violence victims. There is a great necessity to include the
      discipline in the curriculum of healthcare courses permanently. 

PMID- 24918893
TI  - [Patterns of alcohol use and related issues: analysis of nurses' knowledge].
AB  - Descriptive study that aimed to identify and compare the nurses' knowledge
      addressed to patterns of alcohol use and related issues. The study included 185
      nurses of which 84 had attended a training course on the subject. Data were
      collected through a questionnaire of knowledge showing that while the trained
      group obtained the highest average on correct answers, there was a lack of
      knowledge in both groups, especially with regard to the identification of
      complications from alcohol use. Important definitions to nursing practice in the
      area of addictions are presented, suggesting that future training may consider
      the various dimensions involved in caring for people with problems related to
      alcohol. 

PMID- 24918894
TI  - [The construction of ethical competence in the perception of primary care
      nurses].
AB  - The study intended to understand the perception of nurses of Primary Care
      Services about the construction of ethical competence on their formation and
      practices. This is a qualitative study, with an interpretative phenomenological
      approach and interviews with ten nurses of the community health services of Porto
      Alegre, RS. The results showed that the interviewed professionals had already
      experienced situations with ethical conflicts and knew what ethical competence
      means. The central themes point out three fundamental issues in the construction
      of the ethical competence: personal values, education and practice. Taking into
      account that ethical competence is in permanent construction, the study shows the
      importance to promote organizational and educational activities in a transversal
      manner, as a tool to cope the moral stress and contribute in improving the
      quality of care in the primary health attention. 

PMID- 24918895
TI  - [Integrative review: concepts and methods used in nursing].
AB  - Integrative review (IR) has an international reputation in nursing research and
      evidence-based practice. This IR aimed at identifying and analyzing the concepts
      and methods recommended to undertaking IR in nursing. Nine information
      resources,including electronic databases and grey literature were searched.
      Seventeen studies were included. The results indicate that: primary studies were
      mostly from USA; it is possible to have several research questions or hypotheses
      and include primary studies in the review from different theoretical and
      methodological approaches; it is a type of review that can go beyond the analysis
      and synthesis of findings from primary studies allowing exploiting other research
      dimensions, and that presents potentialities for the development of new theories
      and new problems for research. CONCLUSION: IR is understood as a very complex
      type of review and it is expected to be developed using standardized and
      systematic methods to ensure the required rigor of scientific research and
      therefore the legitimacy of the established evidence.

PMID- 24918896
TI  - [Injuries resulted from breastfeeding: a new approach to a known problem].
AB  - This study aimed at analyzing nipple trauma resulted from breastfeeding based on
      dermatological approach. Two integrative reviews of literature were conducted,
      the first related to definitions, classification and evaluation methods of nipple
      trauma and another about validation studies related to this theme. In the first
      part were included 20 studies and only one third defined nipple trauma, more than
      half did not defined the nipple's injuries reported, and each author showed a
      particular way to assess the injuries, without consensus. In the second
      integrative review, no validation study or algorithm related to nipple trauma
      resulted from breastfeeding was found. This fact demonstrated that the nipple's
      injuries mentioned in the first review did not go through validation studies,
      justifying the lack of consensus identified as far as definition, classification
      and assessment methods of nipple trauma. 

PMID- 24918897
TI  - [Health-related quality of life among patients with advanced cancer: an
      integrative review].
AB  - This integrative literature review aimed to characterize scientific articles on
      health-related quality of life - HRQoL - among patients with advanced cancer from
      national and international literature, and summarize those factors evidenced in
      the literature that contributed to the improvement or worsening of HRQoL among
      patients with advanced cancer. The search for materials was conducted in the
      following databases: CINAHL, EMBASE, PubMed, SciELO and LILACS. Among the 21
      articles in the sample, 13 showed an improvement of HRQoL among patients with
      advanced cancer related to the development of physical, emotional and spiritual
      interventions. In eight studies, we identified predictive symptoms of low HRQoL,
      such as pain, fatigue, sleep disorders, depression, nutritional changes, and
      others. The results showed that clinical manifestations, which many times were
      inherent in cancer, such as factors that can lower patients' HRQoL, while
      physical, psychological and spiritual benefits resulting from therapeutic
      interventions may promote its improvement. 

PMID- 24918898
TI  - [Measuring instruments in cardiology adapted into Portuguese language of Brazil:
      a systematic review].
AB  - This was a systematic review aimed at identifying and characterizing measuring
      instruments, developed in the context of cardiology, which were adapted into
      Portuguese language of Brazil. Systematic searches were performed in six
      databases. Information extracted included cultural adaptation process and
      measurement properties. To assess the methodological quality of studies, criteria
      based on international guidelines for cultural adaptation of instruments were
      used. Among the 114 articles found, 14 were eligible for review. Of these, most
      evaluated quality of life (35.7%) and health knowledge/learning (28.6%). Most
      studies followed all stages of the adaptation process recommended in the
      literature. With respect to measurement properties, internal consistency,
      verified by Cronbach's alpha, was the property reported in the majority of the
      studies, as well as construct and criterion validity. This study is expected to
      provide to the scientific community a critical evaluation of adapted
      questionnaires available in the context of cardiology. 

PMID- 24918899
TI  - Transversus abdominis plane block in children: a multicenter safety analysis of
      1994 cases from the PRAN (Pediatric Regional Anesthesia Network) database.
AB  - BACKGROUND: Currently, there is not enough evidence to support the safety of the
      transversus abdominis plane (TAP) block when used to ameliorate postoperative
      pain in children. Safety concerns have been repeatedly mentioned as a major
      barrier to performing large randomized trials in children. The main objective of
      the current investigation was to determine the incidence of overall and specific
      complications resulting from the performance of the TAP block in children. In
      addition, we evaluated patterns of local anesthetic dosage selection in the same
      population. METHODS: This was an observational study using the Pediatric Regional
      Anesthesia Network database. A complication from the TAP block was defined by the
      presence of at least one of the following intraoperative and/or postoperative
      factors: puncture of the peritoneum or organs, vascular puncture, cardiovascular,
      pulmonary and/or neurological symptoms/signs, hematoma, and infection. Additional
      analyses were performed to identify patterns of local anesthetic dosage. RESULTS:
      One thousand nine hundred ninety-four children receiving a TAP block were
      included in the analysis. Only 2 complications were reported: a vascular
      aspiration of blood before local anesthetic injection and a peritoneal puncture
      resulting in an overall incidence of complications (95% CI) of 0.1% (0.02%-0.3%)
      and a specific incidence of complications (vascular aspiration or peritoneal
      puncture) of 0.05% (0.0054%-0.2000%). Neither of these complications resulted in
      additional interventions or sequelae. The median (95% range) for the local
      anesthetic dose per weight for bilateral TAP blocks was 1.0 (0.47-2.29) mg of
      bupivacaine equivalents per kilogram; however, subjects' weights were not
      sufficient to explain much of the variability in dose. One hundred thirty-five of
      1944 (6.9%; 95% CI, 5.8%-8.1%) subjects received doses that could be potentially
      toxic. Subjects who received potentially toxic doses were younger than subjects
      who did not receive potentially toxic doses, 64 (19-100) months and 108 (45-158)
      months, respectively (P < 0.001). CONCLUSIONS: The upper incidence of overall
      complications associated with the TAP block in children was 0.3%. More important,
      complications were very minor and did not require any additional interventions.
      In contrast, the large variability of local anesthetic dosage used can not only
      minimize potential analgesic benefits of the TAP block but also result in local
      anesthetic toxicity. Safety concerns should not be a major barrier to performing
      randomized trials to test the efficacy of the TAP block in children as long as
      appropriate local anesthetic dose regimens are selected.

PMID- 24918900
TI  - Critical appraisal of inflammatory markers in cardiovascular risk stratification.
AB  - Despite great progress in prevention strategies, pharmacotherapy and
      interventional treatment of coronary artery disease (CAD), cardiovascular events
      still constitute the leading cause of mortality and morbidity in the modern
      world. Traditional risk factors, including hypertension, diabetes mellitus,
      smoking, obesity, dyslipidemia, and positive family history account for the
      occurrence of the majority of these events, but not all of them. Adequate risk
      assessment remains the most challenging in individuals classified into low or
      intermediate risk categories. Inflammation plays a key role in the initiation and
      promotion of atherosclerosis and may lead to acute coronary syndrome (ACS) by the
      induction of plaque instability. For this reason, numerous inflammatory markers
      have been extensively investigated as potential candidates for the enhancement of
      cardiovascular risk assessment. This review aims to critically assess the
      clinical utility of well-established (C-reactive protein [CRP] and fibrinogen),
      newer (lipoprotein-associated phospholipase A2 [Lp-PLA2] and myeloperoxidase
      [MPO]) and novel (growth differentiation factor-15 [GDF-15]) inflammatory markers
      which, reflect different pathophysiological pathways underlying CAD. Although
      according to the traditional approach all discussed inflammatory markers were
      shown to be associated with the risk of future cardiovascular events in
      individuals with and without CAD, their clear clinical utility remains not fully
      elucidated. Current recommendations of numerous scientific societies
      predominantly advocate routine assessment of CRP in healthy people with
      intermediate cardiovascular risk. However, these recommendations substantially
      vary in their strength among particular societies. These discrepancies have a
      multifactorial background, including: (i) the strong prognostic value of CRP
      supported by solid scientific evidence and proven to be comparable in magnitude
      with that of total and high-density lipoprotein cholesterol, or hypertension,
      (ii) favourable analytical characteristics of commercially available CRP assays,
      (iii) lack of CRP specificity and causal relationship between CRP concentration
      and cardiovascular risk, and (iv) CRP dependence on other classical risk factors.
      Of major importance, CRP measurement in healthy men >=50 years of age or healthy
      women >=60 years of age with low-density lipoprotein cholesterol <130 mg/dL may
      be helpful in the selection of patients for statin therapy. Additionally,
      evaluation of CRP and fibrinogen or Lp-PLA2 may be considered to facilitate risk
      stratification in ACS patients and in healthy individuals with intermediate
      cardiovascular risk, respectively. Nevertheless, the clinical utility of CRP
      requires further investigation in a broad spectrum of CAD patients, while other
      promising inflammatory markers, particularly GDF-15 and Lp-PLA2, should be tested
      in individuals both with and without established CAD. Further studies should also
      focus on novel performance metrics such as measures of discrimination,
      calibration and reclassification, in order to better address the clinical utility
      of investigated biomarkers and to avoid misleadingly optimistic results. It also
      has to be emphasized that, due to the multifactorial pathogenesis of CAD,
      detailed risk stratification remains a complex process also involving, beyond
      assessment of inflammatory biomarkers, the patient's clinical characteristics,
      results of imaging examinations, electrocardiographic findings and other
      laboratory parameters (e.g. lipid profile, indices of renal function, markers of
      left ventricular overload and fibrosis, and biomarkers of myocardial necrosis,
      preferably cardiac troponins).

PMID- 24918901
TI  - Topological quantum phase transitions and edge states in spin-orbital coupled
      Fermi gases.
AB  - We study superconducting states in the presence of spin-orbital coupling and
      Zeeman field. It is found that a phase transition from a Fulde-Ferrell-Larkin
      Ovchinnikov state to the topological superconducting state occurs upon increasing
      the spin-orbital coupling. The nature of this topological phase transition and
      its critical property are investigated numerically. Physical properties of the
      topological superconducting phase are also explored. Moreover, the local density
      of states is calculated, through which the topological feature may be tested
      experimentally. 

PMID- 24918902
TI  - Magnetic quantum coherence effect in Ni4 molecular transistors.
AB  - We present a theoretical study of electron transport in Ni4 molecular transistors
      in the presence of Zeeman spin splitting and magnetic quantum coherence (MQC).
      The Zeeman interaction is extended along the leads which produces gaps in the
      energy spectrum which allow electron transport with spin polarized along a
      certain direction. We show that the coherent states in resonance with the spin up
      or down states in the leads induces an effective coupling between localized spin
      states and continuum spin states in the single molecule magnet and leads,
      respectively. We investigate the conductance at zero temperature as a function of
      the applied bias and magnetic field by means of the Landauer formula, and show
      that the MQC is responsible for the appearence of resonances. Accordingly, we
      name them MQC resonances. 

PMID- 24918903
TI  - Transoral incisionless fundoplication for the treatment of gastroesophageal
      reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a common and costly chronic medical
      condition affecting millions of patients. It is associated with substantial
      morbidity and negatively impacts quality of life. Reflux of gastric contents into
      the esophagus damages the esophageal mucosa and is associated with conditions
      including esophagitis and esophageal stricture. While GERD is most commonly seen
      in Western populations, changes in dietary patterns and the global increase in
      obesity have led to a pronounced increase in its prevalence worldwide. Medical
      and surgical GERD therapies are costly and pose considerable side effects,
      leading many to pursue effective endoscopic treatment options. Transoral
      incisionless fundoplication is an endoluminal procedure that offers patients a
      minimally invasive treatment option with the potential to eliminate the need for
      medical acid suppression with a low risk of side effects. 

PMID- 24918904
TI  - Hemodynamic impact of cerebral aneurysm endovascular treatment devices: coils and
      flow diverters.
AB  - Coils and flow diverters or stents are devices successfully used to treat
      cerebral aneurysms. Treatment aims to reduce intra-aneurysmal flow, thereby
      separating the aneurysmal sac from the blood circulation. The focus and this
      manuscript combining literature review and our original research is an analysis
      of changes in aneurysmal hemodynamics caused by endovascular treatment devices.
      Knowledge of post-treatment hemodynamics is a path to successful long-term
      treatment. Summarizing findings on hemodynamic impact of treatment devices, we
      conclude: coiling and stenting do not affect post-treatment intra-aneurysmal
      pressure, but significantly alter aneurysmal hemodynamics through flow reduction
      and a change in flow structure. The impact of treatment devices on aneurysmal
      flow depends, however, on a set of parameters including device geometry, course
      of placement, parent vessel and aneurysm geometry. 

PMID- 24918905
TI  - Exposure controls for nanomaterials at three manufacturing sites.
AB  - Because nanomaterials are thought to be more biologically active than their
      larger parent compounds, careful control of exposures to nanomaterials is
      recommended. Field studies were conducted at three sites to develop information
      about the effectiveness of control measures including process changes, a downflow
      room, a ventilated enclosure, and an enclosed reactor. Aerosol mass and number
      concentrations were measured during specific operations with a photometer and an
      electrical mobility particle sizer to provide concentration measurements across a
      broad range of sizes (from 5.6 nm to 30 MUm). At site A, the dust exposure and
      during product harvesting was eliminated by implementing a wait time of 30 -min
      following process completion. And, the dust exposure attributed to process tank
      cleaning was reduced from 0.7 to 0.2 mg/m3 by operating the available process
      ventilation during this task. At site B, a ventilated enclosure was used to
      control dust generated by the manual weigh-out and manipulation of powdered
      nanomaterials inside of a downflow room. Dust exposures were at room background
      (under 0.04 mg/m3 and 500 particles/cm3) during these tasks however,
      manipulations conducted outside of the enclosure were correlated with a transient
      increase in concentration measured at the source. At site C, a digitally
      controlled reactor was used to produce aligned carbon nanotubes. This reactor was
      a closed system and the ventilation functioned as a redundant control measure.
      Process emissions were well controlled by this system with the exception of
      increased concentrations measured during the unloading of the product. However,
      this emission source could be easily controlled through increasing cabinet
      ventilation. The identification and adoption of effective control technologies is
      an important first step in reducing the risk associated with worker exposure to
      engineered nanoparticles. Properly designing and evaluating the effectiveness of
      these controls is a key component in a comprehensive health and safety program.

PMID- 24918906
TI  - Ocean net heat flux influences seasonal to interannual patterns of plankton
      abundance.
AB  - Changes in the net heat flux (NHF) into the ocean have profound impacts on global
      climate. We analyse a long-term plankton time-series and show that the NHF is a
      critical indicator of ecosystem dynamics. We show that phytoplankton abundance
      and diversity patterns are tightly bounded by the switches between negative and
      positive NHF over an annual cycle. Zooplankton increase before the transition to
      positive NHF in the spring but are constrained by the negative NHF switch in
      autumn. By contrast bacterial diversity is decoupled from either NHF switch, but
      is inversely correlated (r = -0.920) with the magnitude of the NHF. We show that
      the NHF is a robust mechanistic tool for predicting climate change indicators
      such as spring phytoplankton bloom timing and length of the growing season.

PMID- 24918907
TI  - Binding modes of three inhibitors 8CA, F8A and I4A to A-FABP studied based on
      molecular dynamics simulation.
AB  - Adipocyte fatty-acid binding protein (A-FABP) is an important target of drug
      designs treating some diseases related to lipid-mediated biology. Molecular
      dynamics (MD) simulations coupled with solvated interaction energy method (SIE)
      were carried out to study the binding modes of three inhibitors 8CA, F8A and I4A
      to A-FABP. The rank of our predicted binding affinities is in accordance with
      experimental data. The results show that the substitution in the position 5 of N
      benzyl and the seven-membered ring of N-benzyl-indole carboxylic acids strengthen
      the I4A binding, while the substitution in the position 2 of N-benzyl weakens the
      F8A binding. Computational alanine scanning and dynamics analyses were performed
      and the results suggest that the polar interactions of the positively charged
      residue R126 with the three inhibitors provide a significant contribution to
      inhibitor bindings. This polar interaction induces the disappearance of the
      correlated motion of the C terminus of A-FABP relative to the N terminus and
      favors the stability of the binding complex. This study is helpful for the
      rational design of potent inhibitors within the fields of metabolic disease,
      inflammation and atherosclerosis. 

PMID- 24918908
TI  - Genomic and metabolomic profile associated to microalbuminuria.
AB  - To identify factors related with the risk to develop microalbuminuria using
      combined genomic and metabolomic values from a general population study. One
      thousand five hundred and two subjects, Caucasian, more than 18 years,
      representative of the general population, were included. Blood pressure
      measurement and albumin/creatinine ratio were measured in a urine sample. Using
      SNPlex, 1251 SNPs potentially associated to urinary albumin excretion (UAE) were
      analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a
      Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age
      54 +/- 19, 50.6% men, ACR>30 mg/g in 81 subjects) with high genotyping call rate
      were analysed. A characteristic metabolomic profile, which included products from
      mitochondrial and extra mitochondrial metabolism as well as branched amino acids
      and their derivative signals, were observed in microalbuminuric as compare to
      normoalbuminuric subjects. The comparison of the metabolomic profile between
      subjects with different UAE status for each of the genotypes associated to
      microalbuminuria revealed two SNPs, the rs10492025_TT of RPH3A gene and the
      rs4359_CC of ACE gene, with minimal or no statistically significant differences.
      Subjects with and without microalbuminuria, who shared the same genotype and
      metabolomic profile, differed in age. Microalbuminurics with the CC genotype of
      the rs4359 polymorphism and with the TT genotype of the rs10492025 polymorphism
      were seven years older and seventeen years younger, respectively as compared to
      the whole microalbuminuric subjects. With the same metabolomic environment,
      characteristic of subjects with microalbuminuria, the TT genotype of the
      rs10492025 polymorphism seems to increase and the CC genotype of the rs4359
      polymorphism seems to reduce risk to develop microalbuminuria.

PMID- 24918909
TI  - Trajectories of cardiovascular health: life course epidemiology in Brazil.

PMID- 24918910
TI  - I cardiovascular prevention guideline of the Brazilian Society of Cardiology -
      executive summary.

PMID- 24918911
TI  - Effects of skeletonized versus pedicled radial artery on postoperative graft
      patency and flow.
AB  - BACKGROUND: Radial artery (RA) was the second arterial graft introduced in
      clinical practice for myocardial revascularization. The skeletonization technique
      of the left internal thoracic artery (LITA) may actually change the graft's flow
      capacity with potential advantages. This leads to the assumption that the
      behavior of the RA, as a coronary graft, is similar to that of the LITA, when
      skeletonized. OBJECTIVE: This study evaluated 'free' aortic-coronary radial
      artery (RA) grafts, whether skeletonized or with adjacent tissues. METHODS: A
      prospective randomized study comparing 40 patients distributed into two groups
      was conducted. In group I, we used skeletonized radial arteries (20 patients),
      and in group II, we used radial arteries with adjacent tissues (20 patients).
      After the surgical procedure, patients underwent flow velocity measurements.
      RESULTS: The main surgical variables were: RA internal diameter, RA length, and
      free blood flow in the radial artery. The mean RA graft diameters as calculated
      using quantitative angiography in the immediate postoperative period were
      similar, as well as the flow velocity measurement variables. On the other hand,
      coronary cineangiography showed the presence of occlusion in one RA graft and
      stenosis in five RA grafts in GII, while GI presented stenosis in only one RA
      graft (p = 0.045). CONCLUSION: These results show that the morphological and
      pathological features, as well as the hemodynamic performance of the free radial
      artery grafts, whether prepared in a skeletonized manner or with adjacent
      tissues, are similar. However, a larger number of non-obstructive lesions may be
      observed when RA is prepared with adjacent tissues.

PMID- 24918912
TI  - Relationship between fibrosis and ventricular arrhythmias in Chagas heart disease
      without ventricular dysfunction.
AB  - BACKGROUND: Patients with Chagas disease and segmental wall motion abnormality
      (SWMA) have worse prognosis independent of left ventricular ejection fraction
      (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect
      SWMA and to assess fibrosis. OBJECTIVE: To quantify fibrosis by using late
      gadolinium enhancement CMR in patients with Chagas disease and preserved or
      minimally impaired ventricular function (> 45%), and to detect patterns of
      dependence between fibrosis, SWMA and LVEF in the presence of ventricular
      arrhythmia. METHODS: Electrocardiogram, treadmill exercise test, Holter and CMR
      were carried out in 61 patients, who were divided into three groups as follows:
      (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram
      and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram.
      RESULTS: The number of patients with ventricular arrhythmia in relation to the
      total of patients, the percentage of fibrosis, and the LVEF were, respectively:
      Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3,
      11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the
      patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87%
      and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%,
      respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the
      latter was significant for the presence of ventricular arrhythmia, with a cutoff
      point of 11.78% for fibrosis mass (p < 0.001). CONCLUSION: Even in patients with
      Chagas disease and preserved or minimally impaired ventricular function,
      electrical instability can be present. Regarding the presence of ventricular
      arrhythmia, fibrosis is the most important variable, its amount being
      proportional to the complexity of the groups.

PMID- 24918913
TI  - LINE-1 hypomethylation is associated with the risk of coronary heart disease in
      Chinese population.
AB  - BACKGROUND: Global methylation level in blood leukocyte DNA has been associated
      with the risk of coronary heart disease (CHD), with inconsistent results in
      various populations. Similar data are lacking in Chinese population where
      different genetic, lifestyle and environmental factors may affect DNA methylation
      and its risk relationship with CHD. OBJECTIVES: To examine whether global
      methylation is associated with the risk of CHD in Chinese population. METHODS: A
      total of 334 cases with CHD and 788 healthy controls were included. Global
      methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats
      using bisulfite pyrosequencing. RESULTS: In an initial analysis restricted to
      control subjects, LINE-1 level reduced significantly with aging, elevated total
      cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced
      LINE-1 methylation was associated with increased risk of CHD; analysis by
      quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3
      (1.6-3.5) for the third, second and first (lowest) quartile (Ptrend < 0.001),
      respectively, compared to the fourth (highest) quartile. Lower (<median) LINE-1
      methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of
      CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among
      subjects with the highest tertile of homocysteine (Pinteraction = 0.042) and
      those with diagnosis of hypertension (Pinteraction = 0.012). CONCLUSION: LINE-1
      hypomethylation is associated with the risk of CHD in Chinese population.
      Potential CHD risk factors such as older age, elevated total cholesterol, and
      diagnosis of diabetes may have impact on global DNA methylation, whereby exerting
      their effect on CHD risk.

PMID- 24918914
TI  - Incidence of ventricular arrhythmias after stem cell therapy in patients with
      Chagas cardiomyopathy.
AB  - BACKGROUND: Treatment with stem cells in several cardiomyopathies may be related
      to the increase in arrhythmias. OBJECTIVES: To determine whether intracoronary
      injection of stem cells in patients with Chagas cardiomyopathy is associated with
      increased incidence of ventricular arrhythmias, compared to the Control Group.
      METHODS: A retrospective cohort study that evaluated the medical records of 60
      patients who participated in a previous cross-sectional study. The following data
      were collected: age, gender, drugs used and Holter variables that demonstrated
      the presence of arrhythmias. Holter was performed in four stages: randomization,
      2, 6 and 12 months segments. The Control Group received medical treatment and
      intracoronary injection of placebo and the Study Group had drug treatment and
      autologous stem cell implant. RESULTS: There was no difference between Control
      Group and Study Group when analyzing the arrhythmia criteria. In the intra-group
      analysis, significant difference was found between the Holter tests of the Study
      Group for the variable total ventricular premature beats when compared with
      baseline, with p = 0.014 between Holter at randomization and Holter at 2 months,
      p = 0.004 between Holter at randomization and Holter at 6 months, and p = 0.014
      between Holter at randomization and Holter at 12 months. The variable non
      sustained ventricular tachycardia between Holter at randomization and Holter at 6
      months showed p = 0.036. CONCLUSION: The intracoronary injection of stem cells
      did not increase the incidence of ventricular arrhythmias in patients with Chagas
      cardiomyopathy compared to the Control Group.

PMID- 24918915
TI  - Systems biology applied to heart failure with normal ejection fraction.
AB  - Heart failure with normal ejection fraction (HFNEF) is currently the most
      prevalent clinical phenotype of heart failure. However, the treatments available
      have shown no reduction in mortality so far. Advances in the omics sciences and
      techniques of high data processing used in molecular biology have enabled the
      development of an integrating approach to HFNEF based on systems biology. This
      study aimed at presenting a systems-biology-based HFNEF model using the bottom-up
      and top-down approaches. A literature search was conducted for studies published
      between 1991 and 2013 regarding HFNEF pathophysiology, its biomarkers and systems
      biology. A conceptual model was developed using bottom-up and top-down approaches
      of systems biology. The use of systems-biology approaches for HFNEF, a complex
      clinical syndrome, can be useful to better understand its pathophysiology and to
      discover new therapeutic targets.

PMID- 24918916
TI  - Obesity and abnormalities in echocardiographic parameters.

PMID- 24918917
TI  - Extracellular matrix turnover: a balance between MMPs and their inhibitors.

PMID- 24918918
TI  - Case 2/2014 - 51-year old patient with systemic lupus erythematosus and fever
      after valve replacement.

PMID- 24918919
TI  - Prolonged cardiopulmonary arrest treated successfully in the Sao Paulo's subway.

PMID- 24918920
TI  - Is heart team fundamental to aortic stenosis transcatheter treatment?

PMID- 24918921
TI  - Virus enrichment for single virus infection by using 3D insulator based
      dielectrophoresis.
AB  - We developed an active virus filter (AVF) that enables virus enrichment for
      single virus infection, by using insulator-based dielectrophoresis (iDEP). A 3D
      constricted flow channel design enabled the production of an iDEP force in the
      microfluidic chip. iDEP using a chip with multiple active virus filters (AVFs)
      was more accurate and faster than using a chip with a single AVF, and improved
      the efficiency of virus trapping. We utilized maskless photolithography to
      achieve the precise 3D gray-scale exposure required for fabrication of
      constricted flow channel. Influenza virus (A PR/8) was enriched by a negative DEP
      force when sinusoidal wave was applied to the electrodes within an amplitude
      range of 20 Vp-p and a frequency of 10 MHz. AVF-mediated virus enrichment can be
      repeated simply by turning the current ON or OFF. Furthermore, the negative AVF
      can inhibit virus adhesion onto the glass substrate. We then trapped and
      transported one of the enriched viruses by using optical tweezers. This
      microfluidic chip facilitated the effective transport of a single virus from AVFs
      towards the cell-containing chamber without crossing an electrode. We
      successfully transported the virus to the cell chamber (v = 10 um/s) and brought
      it infected with a selected single H292 cell.

PMID- 24918922
TI  - Spatial heterogeneity in response of male greater sage-grouse lek attendance to
      energy development.
AB  - Landscape modification due to rapidly expanding energy development, in particular
      oil and gas, in the westernUSA, have prompted concerns over how such developments
      may impact wildlife. One species of conservation concern across much of the
      Intermountain West is the greater sage-grouse (Centrocercusurophasianus). Sage
      grouse have been petitioned for listing under provisions of the Endangered
      Species Act 7 times and the state of Wyoming alone represents 64% of the extant
      sage-grouse population in the eastern portion of their range. Consequently, the
      relationship between sage-grouse populations and oil and gas development in
      Wyoming is an important component to managing the long-term viability of this
      species. We used 814 leks from the Wyoming Game and Fish Department's lek survey
      database and well pad data from the Wyoming Oil and Gas Conservation Commission
      to evaluate changes in sage-grouse lek counts as a function of oil and gas
      development since 1991.From 1991-2011 we found that oil and gas well-pad density
      increased 3.6-fold across the state and was associated with a 24% decline in the
      number of male sage-grouse. Using a spatial and temporally structured analysis
      via Geographically Weighted Regression, we found a 1-to-4 year time lag between
      development density and lek decline. Sage-grouse also responded to development
      densities at multiple spatial neighborhoods surrounding leks, including broad
      scales of 10 km. However, sage-grouse lek counts do not always decline as a
      result of oil and gas development. We found similar development densities
      resulting in different sage-grouse lek count responses, suggesting that
      development density alone is insufficient to predict the impacts that oil and gas
      development have on sage-grouse. Finally, our analysis suggests a maximum
      development density of 1 well-pad within 2 km of leks to avoid measurable impacts
      within 1 year, and <6 well-pads within 10 km of leks to avoid delayed impacts. 

PMID- 24918923
TI  - Riproximin's activity depends on gene expression and sensitizes PDAC cells to
      TRAIL.
AB  - Riproximin (Rpx) is a type II ribosome inactivating protein, which was
      investigated for its activity in pancreatic ductal adenocarcinoma (PDAC) in a
      panel of 17 human and rat PDAC cell lines and in rat pancreatic cancer liver
      metastasis. Cytotoxicity in response to Rpx was determined by MTT assay,
      apoptosis by flow cytometry and qRT-PCR for apoptosis related genes, and the
      modulation of the transcriptome was monitored by micro array analysis. The
      combination effect of Rpx and TRAIL was assessed by MTT assay. Rpx showed high
      but varying cytotoxicity in PDAC cells. Based on overall gene expression, the
      sensitivity of these cells was linked to genes involved in apoptosis.
      Furthermore, based on the affinity of Rpx for CEA, the expression of
      carcinoembryonic antigen-related cell adhesion molecule (CEACAM) genes was
      significantly related to Rpx's cytotoxicity in cells with CEACAM gene expression.
      Exposure of Suit2-007 cells to Rpx induced the mRNA expression of members of
      signaling pathways initiating from most death receptors, and down modulation of
      TRAIL. Apoptosis was increased as shown by FACS analysis. Combination of Rpx with
      TRAIL resulted in a synergistic cytotoxic effect in human Suit2-007 and rat ASML
      cells, as evidenced by a 6-fold lower tumor cell survival than expected from an
      additive combination effect. Treatment of BDX rats bearing intra-portally
      implanted Suit2-007 cells showed a highly significant anticancer effect and
      indicated an application of Rpx against pancreatic cancer metastasis to the
      liver. These data favor further evaluation of Rpx as anticancer agent in PDAC. 

PMID- 24918924
TI  - Toll-like receptor 4 mediates endothelial cell activation through NF-kappaB but
      is not associated with endothelial dysfunction in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the effects of TLR4 antagonism on human endothelial
      cells activation and cytokine expression, and whether the Asp299Gly TLR4
      polymorphism is associated with better endothelial function in patients with
      rheumatoid arthritis (RA). METHODS: Human aortic endothelial cells (HAECs) were
      treated with lipopolysaccharide (LPS), OxPAPC, and free fatty acids (FFA) at
      baseline and after incubation with the TLR4 antagonist eritoran (E5564). Cytokine
      expression was assessed by quantitative real-time PCR. In vivo endothelial
      function was assessed as brachial artery flow-mediated dilation (FMD) in RA
      patients with the wild type gene (aa) and with the Asp299Gly TLR4 polymorphic
      variant (ag). RESULTS: In HAEC, TLR4 antagonism with eritoran inhibited LPS
      induced mRNA expression of IL-6, IL-8, TNFalpha, CCL-2, VCAM and ICAM (P<0.05 for
      all) and inhibited Ox-PAPC-induced mRNA expression of IL-8 (P<0.05) and IL-6,
      albeit not to a statistically significant level (p = 0.07). In contrast, eritoran
      did not affect FFA-induced mRNA expression of IL-6 (P>0.05). In 30 patients with
      RA (15 with the ag allele) undergoing measurement of FMD, no differences in FMD
      and plasma levels of IL-6, IL-8, VCAM, and ICAM were found between the aa and the
      ag phenotype (P>0.05 for all). CONCLUSIONS: TLR4 signaling in endothelial cells
      may be triggered by LPS and oxidized phospholipids, leading to endothelial
      activation and inflammation, which are inhibited by eritoran. Our in vivo
      investigation, however, does not support an association between the Asp299Gly
      TLR4 polymorphism and improved endothelium-dependent vasodilator function in
      patients with RA. Further study is needed to better understand the potential role
      of TLR4 on endothelial dysfunction in this and other patient populations.

PMID- 24918925
TI  - Nontuberculous mycobacterial infection is associated with increased respiratory
      failure: a nationwide cohort study.
AB  - BACKGROUND AND PURPOSE: Population study on relationship between nontuberculous
      mycobacterial (NTM) infection and respiratory failure (RF) is limited. This study
      evaluated the RF risk, including acute respiratory failure (ARF), chronic
      respiratory failure (CRF) and ARF on CRF, in patients with NTM infection in
      Taiwan. METHODS: We used the National Health Insurance Research Database of
      Taiwan to identify 3864 newly diagnosed NTM patients (NTM cohort) from 1999 to
      2009, and 15456 non-NTM patients (non-NTM cohort), frequency matched by
      demographic status for comparison. Incidence and hazard of developing RF were
      measured by the end of 2010. RESULTS: The incidence rate of RF was 4.31-fold
      higher in the NTM cohort than in the non-NTM cohort (44.0 vs.10.2 per 1000 person
      years), with an adjusted hazard ratio (HR) of 3.11 (95% CI: 2.73-3.54). The
      cumulative proportional incidence of RF was 10% higher in the NTM cohort than in
      the non-NTM cohort (P<0.0001). The RF risk was much greater within 6 months after
      the diagnosis of NTM infection with a HR of 7.45 (95% CI = 5.50-10.09). Age
      specific comparison showed that the younger NTM patients had a higher HR of RF
      than the elderly NTM patients (HR: 4.42, 95% CI: 3.28-5.96 vs. HR: 2.52, 95% CI:
      2.17-2.92). Comorbidity increased the risk of RF in both cohorts, particularly in
      those with chronic obstructive pulmonary disease. CONCLUSION: Our study suggests
      patients with NTM infection are at a high risk of RF. The risk appears much
      greater soon after patients diagnosed with NTM infection.

PMID- 24918926
TI  - Adaptive evolution of mitochondrial energy metabolism genes associated with
      increased energy demand in flying insects.
AB  - Insects are unique among invertebrates for their ability to fly, which raises
      intriguing questions about how energy metabolism in insects evolved and changed
      along with flight. Although physiological studies indicated that energy
      consumption differs between flying and non-flying insects, the evolution of
      molecular energy metabolism mechanisms in insects remains largely unexplored.
      Considering that about 95% of adenosine triphosphate (ATP) is supplied by
      mitochondria via oxidative phosphorylation, we examined 13 mitochondrial protein
      encoding genes to test whether adaptive evolution of energy metabolism-related
      genes occurred in insects. The analyses demonstrated that mitochondrial DNA
      protein-encoding genes are subject to positive selection from the last common
      ancestor of Pterygota, which evolved primitive flight ability. Positive selection
      was also found in insects with flight ability, whereas no significant sign of
      selection was found in flightless insects where the wings had degenerated. In
      addition, significant positive selection was also identified in the last common
      ancestor of Neoptera, which changed its flight mode from direct to indirect.
      Interestingly, detection of more positively selected genes in indirect flight
      rather than direct flight insects suggested a stronger selective pressure in
      insects having higher energy consumption. In conclusion, mitochondrial protein
      encoding genes involved in energy metabolism were targets of adaptive evolution
      in response to increased energy demands that arose during the evolution of flight
      ability in insects. 

PMID- 24918927
TI  - RIG-I enhanced interferon independent apoptosis upon Junin virus infection.
AB  - Junin virus (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF),
      a human disease with a high case-fatality rate. It is widely accepted that
      arenaviral infections, including JUNV infections, are generally non-cytopathic.
      In contrast, here we demonstrated apoptosis induction in human lung epithelial
      carcinoma (A549), human hepatocarcinoma and Vero cells upon infection with the
      attenuated Candid#1 strain of, JUNV as determined by phosphatidylserine (PS)
      translocation, Caspase 3 (CASP3) activation, Poly (ADP-ribose) polymerase (PARP)
      cleavage and/or chromosomal DNA fragmentation. Moreover, as determined by DNA
      fragmentation, we found that the pathogenic Romero strain of JUNV was less
      cytopathic than Candid#1 in human hepatocarcinoma and Vero, but more apoptotic in
      A549 and Vero E6 cells. Additionally, we found that JUNV-induced apoptosis was
      enhanced by RIG-I signaling. Consistent with the previously reported role of RIG
      I like helicase (RLH) signaling in initiating programmed cell death, we showed
      that cell death or DNA fragmentation of Candid#1-infected A549 cells was
      decreased upon siRNA or shRNA silencing of components of RIG-I pathway in spite
      of increased virus production. Similarly, we observed decreased DNA fragmentation
      in JUNV-infected human hepatocarcinoma cells deficient for RIG-I when compared
      with that of RIG-I-competent cells. In addition, DNA fragmentation detected upon
      Candid#1 infection of type I interferon (IFN)-deficient Vero cells suggested a
      type I IFN-independent mechanism of apoptosis induction in response to JUNV. Our
      work demonstrated for the first time apoptosis induction in various cells of
      mammalian origin in response to JUNV infection and partial mechanism of this cell
      death. 

PMID- 24918928
TI  - Expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in women
      of Uygur ethnicity from Xinjiang, China.
AB  - BACKGROUND: Overexpression of several aquaporins has been reported in different
      types of human cancer but the role of aquaporins in carcinogenesis has not yet
      been clearly defined. There is few report concerning role of aquaporins in human
      cervical carcinogenesis so far. Here, we determined the expression and prognostic
      value of aquaporin 1, 3 in cervical carcinoma in Chinese women of Uygur
      ethnicity. METHODS AND RESULTS: Real-time PCR analyses demonstrated aquaporin 1,
      3 mRNA were differentially expressed in cervical carcinoma, CIN 2-3 and mild
      cervicitis. Immunofluorescent and immunohistochemical analyses demonstrated
      aquaporin 1 was predominantly localized to stromal endothelial cells in cervical
      lesions. Aquaporin 3 was localized to the membrane of normal squamous epithelium,
      CIN and carcinoma cells. Aquaporin 1 and 3 were upregulated in cervical cancer
      compared to mild cervicitis and CIN2-3 (P<0.05); Tumor expression of aquaporin 1,
      3 significantly increased in advanced stage disease, and patients with deeper
      tumor infiltration, lymph node metastases or larger tumor volume (P<0.05).
      Multivariate analysis demonstrated that aquaporin 1, 3 were not independent
      prognostic factors in cervical carcinoma. CONCLUSION: Aquaporins may participate
      in the initiation and progression of cervical carcinoma by promoting tumor
      growth, invasion or lymph node metastasis. Further study is required to determine
      whether aquaporins have potential as prognostic factors in cervical cancer.

PMID- 24918929
TI  - Paramyxovirus infection regulates T cell responses by BDCA-1+ and BDCA-3+ myeloid
      dendritic cells.
AB  - Respiratory syncytial virus (RSV) and human Metapneumovirus (hMPV), viruses
      belonging to the family Paramyxoviridae, are the most important causes of lower
      respiratory tract infection in young children. Infections with RSV and hMPV are
      clinically indistinguishable, and both RSV and hMPV infection have been
      associated with aberrant adaptive immune responses. Myeloid Dendritic cells
      (mDCs) play a pivotal role in shaping adaptive immune responses during infection;
      however, few studies have examined how interactions of RSV and hMPV with
      individual mDC subsets (BDCA-1(+) and BDCA-3(+) mDCs) affect the outcome of anti
      viral responses. To determine whether RSV and hMPV induce virus-specific
      responses from each subset, we examined co-stimulatory molecules and cytokines
      expressed by BDCA-1(+) and BDCA-3(+) mDCs isolated from peripheral blood after
      infection with hMPV and RSV, and examined their ability to stimulate T cell
      proliferation and differentiation. Our data show that RSV and hMPV induce virus
      specific and subset-specific patterns of co-stimulatory molecule and cytokine
      expression. RSV, but not hMPV, impaired the capacity of infected mDCs to
      stimulate T cell proliferation. Whereas hMPV-infected BDCA-1(+) and BDCA-3(+)
      mDCs induced expansion of Th17 cells, in response to RSV, BDCA-1(+) mDCs induced
      expansion of Th1 cells and BDCA-3(+) mDCs induced expansion of Th2 cells and
      Tregs. These results demonstrate a virus-specific and subset-specific effect of
      RSV and hMPV infection on mDC function, suggesting that these viruses may induce
      different adaptive immune responses.

PMID- 24918930
TI  - Spatiotemporal dynamics of the HIV-1 subtype G epidemic in West and Central
      Africa.
AB  - The human immunodeficiency virus type 1 (HIV-1) subtype G is the second most
      prevalent HIV-1 clade in West Africa, accounting for nearly 30% of infections in
      the region. There is no information about the spatiotemporal dynamics of
      dissemination of this HIV-1 clade in Africa. To this end, we analyzed a total of
      305 HIV-1 subtype G pol sequences isolated from 11 different countries from West
      and Central Africa over a period of 20 years (1992 to 2011). Evolutionary,
      phylogeographic and demographic parameters were jointly estimated from sequence
      data using a Bayesian coalescent-based method. Our analyses indicate that subtype
      G most probably emerged in Central Africa in 1968 (1956-1976). From Central
      Africa, the virus was disseminated to West and West Central Africa at multiple
      times from the middle 1970s onwards. Two subtype G strains probably introduced
      into Nigeria and Togo between the middle and the late 1970s were disseminated
      locally and to neighboring countries, leading to the origin of two major western
      African clades (G WA-I and G WA-II). Subtype G clades circulating in western and
      central African regions displayed an initial phase of exponential growth followed
      by a decline in growth rate since the early/middle 1990 s; but the mean epidemic
      growth rate of G WA-I (0.75 year-1) and G WA-II (0.95 year-1) clades was about
      two times higher than that estimated for central African lineages (0.47 year-1).
      Notably, the overall evolutionary and demographic history of G WA-I and G WA-II
      clades was very similar to that estimated for the CRF06_cpx clade circulating in
      the same region. These results support the notion that the spatiotemporal
      dissemination dynamics of major HIV-1 clades circulating in western Africa have
      probably been shaped by the same ecological factors.

PMID- 24918931
TI  - DP-b99 modulates matrix metalloproteinase activity and neuronal plasticity.
AB  - DP-b99 is a membrane-activated chelator of zinc and calcium ions, recently
      proposed as a therapeutic agent. Matrix metalloproteinases (MMPs) are zinc
      dependent extracellularly operating proteases that might contribute to synaptic
      plasticity, learning and memory under physiological conditions. In excessive
      amounts these enzymes contribute to a number of neuronal pathologies ranging from
      the stroke to neurodegeneration and epileptogenesis. In the present study, we
      report that DP-b99 delays onset and severity of PTZ-induced seizures in mice, as
      well as displays neuroprotective effect on kainate excitotoxicity in hippocampal
      organotypic slices and furthermore blocks morphological reorganization of the
      dendritic spines evoked by a major neuronal MMP, MMP-9. Taken together, our
      findings suggest that DP-b99 may inhibit neuronal plasticity driven by MMPs, in
      particular MMP-9, and thus may be considered as a therapeutic agent under
      conditions of aberrant plasticity, such as those subserving epileptogenesis. 

PMID- 24918932
TI  - Prostaglandin E2 promotes features of replicative senescence in chronically
      activated human CD8+ T cells.
AB  - Prostaglandin E2 (PGE2), a pleiotropic immunomodulatory molecule, and its free
      radical catalyzed isoform, iso-PGE2, are frequently elevated in the context of
      cancer and chronic infection. Previous studies have documented the effects of
      PGE2 on the various CD4+ T cell functions, but little is known about its impact
      on cytotoxic CD8+ T lymphocytes, the immune cells responsible for eliminating
      virally infected and tumor cells. Here we provide the first demonstration of the
      dramatic effects of PGE2 on the progression of human CD8+ T cells toward
      replicative senescence, a terminal dysfunctional state associated multiple
      pathologies during aging and chronic HIV-1 infection. Our data show that exposure
      of chronically activated CD8+ T cells to physiological levels of PGE2 and iso
      PGE2 promotes accelerated acquisition of markers of senescence, including loss of
      CD28 expression, increased expression of p16 cell cycle inhibitor, reduced
      telomerase activity, telomere shortening and diminished production of key
      cytotoxic and survival cytokines. Moreover, the CD8+ T cells also produced higher
      levels of reactive oxygen species, suggesting that the resultant oxidative stress
      may have further enhanced telomere loss. Interestingly, we observed that even
      chronic activation per se resulted in increased CD8+ T cell production of PGE2,
      mediated by higher COX-2 activity, thus inducing a negative feedback loop that
      further inhibits effector function. Collectively, our data suggest that the
      elevated levels of PGE2 and iso-PGE2, seen in various cancers and HIV-1
      infection, may accelerate progression of CD8+ T cells towards replicative
      senescence in vivo. Inhibition of COX-2 activity may, therefore, provide a
      strategy to counteract this effect. 

PMID- 24918933
TI  - Screening for acute HIV infections and estimating HIV incidence among female sex
      workers from low-grade venues in Guangxi, China.
AB  - BACKGROUND: Guangxi has become one of the provinces with the most severe HIV-1
      epidemic in China, where heterosexual contact is the dominant transmission route.
      However, data of acute HIV infections and HIV incidence among female sex workers
      (FSWs) from low-grade venues are scant. METHODS: A cross-sectional survey was
      performed among FSWs from low-grade venues in Guangxi. HIV antibody screening was
      performed by rapid testing (RT). HIV antibody-negative specimens were screened by
      pooled nucleic acid amplification testing (NAAT) for acute HIV infections. HIV
      antibody-positive specimens were further analyzed by Western blot (WB), followed
      by an HIV-1 BED capture enzyme immunoassay (BED-CEIA) to identify the recent
      infections. HIV-1 incidence was estimated by the data of pooled NAAT and BED
      CEIA, respectively. RESULTS: A total of 7936 FSWs were recruited and answered the
      questionnaires. We successfully collected the blood samples from 6469 (81.5%)
      participants, of which 139 (2.1%) were HIV antibody-positive and 6330 (97.9%)
      were HIV antibody-negative by RT. With pooled NAAT, 7 cases were found to be HIV
      RNA positive, representing an additional 5.0% of HIV-infected persons and an
      estimated HIV incidence of 1.45 (95% CI: 1.17-1.76) per 100 person years. There
      were 137 positive and 2 indeterminate by WB, of which 124 (90.5%) positive
      specimens were subjected to BED-CEIA testing identifying 28 recent infections.
      The HIV incidence determined by BED-CEIA testing was 1.04 (95% CI: 0.65-1.43) per
      100 person years. The overall prevalence of HIV among FSWs from low-grade venues
      in Guangxi was 2.2% (95% CI: 1.9-2.6). CONCLUSIONS: We found that the addition of
      HIV RNA screening to routine HIV antibody testing significantly improved the
      detection of HIV infection among FSWs from low-grade venues in Guangxi. Our
      findings also provided the useful baseline data of HIV incidence among this
      population for targeting local HIV prevention, intervention, monitoring and
      treatment.

PMID- 24918934
TI  - Secrets of solid state and aqueous solution structures of [Ni(tmdta)](2-).
AB  - The molecular structures of Li2[Ni(tmdta)].5H2O (1a, tmdta =
      trimethylenediaminetetraacetate), {C(NH2)3}2[Ni(tmdta)].6H2O (1b), and
      {Ni(H2O)6}[Ni(tmdta)].2H2O (2a) have been determined. The central
      trimethylenediamine chelate ring shows half-chair (hc) geometries in 1a and 1b,
      while a twist-boat (tb) conformation is encountered in 2a. The coexistence of tb
      and hc forms in the solid state prompted us to elucidate the existence of a tb ?
      hc equilibrium in aqueous solution. Evaluation of the data from solid state
      vibrational spectra (Raman and IR) for the hc and tb forms showed excellent
      agreement with simulated spectra obtained with DFT computations (TPSSh/TZVP).
      This outstanding matching between theory and experiment enabled us to build
      composite spectra with varying hc:tb ratios. Comparison of these results with
      Raman and IR spectra recorded for [Ni(tmdta)](2-) in aqueous solution revealed
      that simulated Raman and IR spectra with a hc:tb ratio = 2:3 match the solution
      spectra in an accurate way. This equilibrium ratio enabled us to compute (13)C
      NMR sifts for the paramagnetic solution spectrum of [Ni(tmdta)](2-) based on the
      relative contributions by hc and tb fractions. This leads to computed shifts that
      agree closely with the experimental ones. Also, the kinetics of the skeleton
      dynamics could be estimated quantitatively by temperature-dependent (13)C NMR
      spectroscopic measurements. An interesting effect encountered for the very first
      time here concerns a drastic intensity difference of the 10Dq band ((3)A2g ->
      (3)T2g(F) transition) in solid state electronic spectra of tb vs hc isomers,
      where the intensity of this band in the case of the hc form is much lower than
      that of the tb conformer and thus more similar to the case of the usual Ni(II)
      chromophore in octahedral environment. The equilibrium constants for complex
      formation and protonation of Ni(II)-tmdta at low pH have been estimated by pH
      dependent UV-vis titration experiments. Correlation of these data with those of
      Ni(II)-edta and related 3d M(II) edta and tmdta complexes allow important
      conclusions on the consequences resulting from extending the central diamine ring
      in the ligand by one methylene group in terms of both complex and protolytic
      stability for edta vs tmdta complexes. 

PMID- 24918935
TI  - Heading for the hills: risk avoidance drives den site selection in African wild
      dogs.
AB  - Compared to their main competitors, African wild dogs (Lycaon pictus) have
      inferior competitive abilities and interspecific competition is a serious fitness
      limiting factor. Lions (Panthera leo) are the dominant large carnivore in African
      savannah ecosystems and wild dogs avoid them both spatially and temporally. Wild
      dog young are particularly vulnerable and suffer high rates of mortality from
      lions. Since lions do not utilize all parts of the landscape with an equal
      intensity, spatial variation in lion densities can be exploited by wild dogs both
      during their general ranging behaviour, but more specifically when they are
      confined to a den with vulnerable young. Since patches of rugged terrain are
      associated with lower lion densities, we hypothesized that these comparatively
      safe habitats should be selected by wild dogs for denning. We investigated the
      relationship between the distribution of 100 wild dog den sites and the
      occurrence of rugged terrain in four wild dog populations located in Tanzania,
      Zimbabwe and South Africa. A terrain ruggedness index was derived from a 90 m
      digital elevation model and used to map terrain ruggedness at each site. We
      compared characteristics of actual and potential (random) den sites to determine
      how wild dogs select den sites. The distributions of wild dog dens were strongly
      associated with rugged terrain and wild dogs actively selected terrain that was
      more rugged than that available on average. The likelihood of encountering lions
      is reduced in these habitats, minimizing the risk to both adults and pups. Our
      findings have important implications for the conservation management of the
      species, especially when assessing habitat suitability for potential
      reintroductions. The simple technique used to assess terrain ruggedness may be
      useful to investigate habitat suitability, and even predict highly suitable
      denning areas, across large landscapes. 

PMID- 24918936
TI  - Detection of polynucleotide kinase activity by using a gold electrode modified
      with magnetic microspheres coated with titanium dioxide nanoparticles and a DNA
      dendrimer.
AB  - In this paper, we have designed a signal amplified method for the electrochemical
      determination of polynucleotide kinase activity. It is based on (a) the
      peroxidase-like activity of magnetite microspheres (MNPs), (b) the specific
      recognition capabilities of titanium dioxide (TiO2) with the phosphate groups of
      the capture probe and (c) the DNA dendrimer structure for signal amplification.
      MNPs coated with TiO2 (TMNPs) were prepared and characterized by scanning
      electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy.
      TMNP-DNA dendrimers were formed by the hybridization of captured nucleic acids
      with a link probe. Cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) were carried out to study the electrocatalytic process. The
      formation of the TMNP-DNA dendrimer structures was related to the phosphorylated
      capture probe and further to the activity of polynucleotide kinase, which was the
      base of the polynucleotide kinase detection. The TMNP-DNA dendrimer based
      biosensor showed sensitive detection of polynucleotide kinase with a satisfying
      result; a low detection of 0.003 U mL(-1) and wide linear range of 0.01 to 30 U
      mL(-1) were achieved. Additionally, the present TMNP-DNA dendrimer based
      biosensor also demonstrated excellent selectivity, stability and reproducibility.

PMID- 24918937
TI  - Caffeine-induced Ca2+ oscillations in type I horizontal cells of the carp retina
      and the contribution of the store-operated Ca2+ entry pathway.
AB  - The mechanisms of release, depletion, and refilling of endoplasmic reticulum (ER)
      Ca2+ were investigated in type I horizontal cells of the carp retina using a fluo
      3-based Ca2+ imaging technique. Exogenous application of caffeine, a ryanodine
      receptor agonist, induced oscillatory intracellular free Ca2+ concentration
      ([Ca2+]i) responses in a duration- and concentration-dependent manner. In Ca2+
      free Ringer's solution, [Ca2+]i transients could also be induced by a brief
      caffeine application, whereas subsequent caffeine application induced no [Ca2+]i
      increase, which implied that extracellular Ca2+ was required for ER refilling,
      confirming the necessity of a Ca2+ influx pathway for ER refilling. Depletion of
      ER Ca2+ by thapsigargin triggered a Ca2+ influx which could be blocked by the
      store-operated channel inhibitor 2-APB, which proved the existence of the store
      operated Ca2+ entry pathway. Taken together, these results suggested that after
      being depleted by caffeine, the ER was replenished by Ca2+ influx via store
      operated channels. These results reveal the fine modulation of ER Ca2+ signaling,
      and the activation of the store-operated Ca2+ entry pathway guarantees the
      replenishment of the ER so that the cell can be ready for response to the
      subsequent stimulus. 

PMID- 24918938
TI  - Chloride secretion induced by rotavirus is oxidative stress-dependent and
      inhibited by Saccharomyces boulardii in human enterocytes.
AB  - Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms,
      primarily chloride secretion in intestinal epithelial cell. The chloride
      secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity
      in human enterocytes through mechanisms that have not been defined. Redox
      imbalance is a common event in cells infected by viruses, but the role of
      oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion
      in association with an increase in reactive oxygen species (ROS) in Caco-2 cells.
      The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by
      RV. The same effects were observed when purified NSP4 was added to Caco-2 cells.
      N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in
      ROS and GSH imbalance. These results suggest a link between oxidative stress and
      RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively
      used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb
      supernatant prevented RV-induced oxidative stress and strongly inhibited chloride
      secretion in Caco-2 cells. These results were confirmed in an organ culture model
      using human intestinal biopsies, demonstrating that chloride secretion induced by
      RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces
      soluble metabolites that prevent oxidative stress. The results of this study
      provide novel insights into RV-induced diarrhea and the efficacy of probiotics. 

PMID- 24918939
TI  - The perception and mimicry of facial movements predict judgments of smile
      authenticity.
AB  - The mechanisms through which people perceive different types of smiles and judge
      their authenticity remain unclear. Here, 19 different types of smiles were
      created based on the Facial Action Coding System (FACS), using highly controlled,
      dynamic avatar faces. Participants observed short videos of smiles while their
      facial mimicry was measured with electromyography (EMG) over four facial muscles.
      Smile authenticity was judged after each trial. Avatar attractiveness was judged
      once in response to each avatar's neutral face. Results suggest that, in contrast
      to most earlier work using static pictures as stimuli, participants relied less
      on the Duchenne marker (the presence of crow's feet wrinkles around the eyes) in
      their judgments of authenticity. Furthermore, mimicry of smiles occurred in the
      Zygomaticus Major, Orbicularis Oculi, and Corrugator muscles. Consistent with
      theories of embodied cognition, activity in these muscles predicted authenticity
      judgments, suggesting that facial mimicry influences the perception of smiles.
      However, no significant mediation effect of facial mimicry was found. Avatar
      attractiveness did not predict authenticity judgments or mimicry patterns. 

PMID- 24918940
TI  - Laparoscopic management of nonmidline ventral hernia.
AB  - INTRODUCTION: Ventral hernias may be primary or incisional and classified as
      midline ventral hernias (MVHs) or non-MVHs (NMVHs). NMVHs are rarer, and their
      laparoscopic management is technically challenging because of varied anatomic
      locations, differences in patient positioning at time of surgery, and lack of
      adequate lateral space for mesh fixation, compounded by the proximity of major
      organs and bony landmarks. A retrospective review of all the NMVHs operated on in
      a clinical unit is presented. SUBJECTS AND METHODS: One hundred eighty-three
      cases met the criteria of ventral hernia, with 25 cases (13.66%) as NMVH. These
      NMVHs included lumbar (n=5), suprapubic (n=7), iliac (n=10), and subcostal (n=3).
      Univariate and multivariate analyses were done using SPSS version 19 software
      (IBM, Armonk, NY). Continuous data were analyzed using the Mann-Whitney U test/t
      test, and categorical data were analyzed using the chi-squared test. A P value of
      <=.05 was considered significant. RESULTS: Demographic profile and presentation
      were similar in all groups. One case each had seromuscular intestinal injury in
      the iliac group (P=.668), splenic injury in the lumbar group, and liver injury in
      the subcostal group (P=.167). In the iliac group there was 1 patient with
      hematoma (P=.668), whereas seroma was seen in 1 lumbar group patient and 2 iliac
      group patients (P=.518). Persistent cough impulse was seen in 1 case each in the
      iliac and lumbar groups (P=.593). One case in the iliac group recurred after
      primary surgery (P=.668). CONCLUSIONS: NMVHs have a similar spectrum of
      difficulty and complication profile as those of laparoscopic MVH repairs.
      Laparoscopic repair of a non-midline hernia is technically challenging but
      definitely feasible. The incidence of complications and recurrence rate might be
      more than those for MVHs, but its actual validation needs a much larger
      comparative study having a longer follow-up.

PMID- 24918941
TI  - A comparison of neutral and immune genetic variation in Atlantic salmon, Salmo
      salar L. in Chilean aquaculture facilities.
AB  - Genetic diversity was assessed in samples of cultured Atlantic salmon, Salmo
      salar L., obtained from facilities in Chile between 2005 and 2010, a period of
      time during which the infectious pathogens Infectious Salmon Anemia (ISA) virus,
      Caligus rogercresseyi (sea lice), and Piscirickettsia salmonis (salmon
      rickettsial syndrome) were common. Two panels of microsatellite markers were
      utilized: one with microsatellites with no known gene associations (neutral) and
      one featuring microsatellites linked to putative immune-related genes (immune
      related). Allelic richness and gene diversity across samples were significantly
      greater in neutral loci as compared to immune-related loci. Both diversity
      measures were homogeneous among samples for immune-related loci and heterogeneous
      among samples for neutral loci. Immune-related loci were identified as F(ST)
      outliers in pairwise comparisons of samples at a 10-fold higher frequency than
      neutral loci. These results indicate that neutral and immune-related portions of
      the Atlantic salmon genome may have differed in response to the gauntlet of
      pathogens and that monitoring of specific, well characterized immune-related loci
      as well as neutral loci in cultured species could be useful when disease control
      and prevention is a goal.

PMID- 24918942
TI  - Deagrarianisation and forest revegetation in a biodiversity hotspot on the Wild
      Coast, South Africa.
AB  - Deagraianisation is a worldwide phenomenon with widespread social, ecological and
      economic effects yet with little consensus on the local or higher level causes.
      There have been contested views on the causes and consequences of
      deagrarianisation on South Africa's Wild Coast, which is an international
      biodiversity hotspot. Using GIS, household interviews and ecological sampling, we
      compared the perspectives of current and former cultivators as to why some have
      abandoned farming, whilst also tracking the uses and woody plant cover and
      composition of fields abandoned at different periods. The GIS analysis showed
      that field abandonment had been ongoing over several decades, with a decline from
      12.5 % field cover in 1961 to 2.7 % in 2009. The area of forests and woodlands
      almost doubled in the corresponding period. There was a distinct peak in field
      abandonment during the time of political transition at the national level in the
      early 1990 s. This political change led to a decrease in government support for
      livestock farming, which in turn resulted in reduced animal draught power at the
      household and community level, and hence reduced cropping. The study showed it is
      largely the wealthier households that have remained in arable agriculture and
      that the poorer households have abandoned farming. The abandoned fields show a
      distinct trend of increasing woody biomass and species richness with length of
      time since abandonment, with approximately three woody plant species added per
      decade. Most local respondents dislike the increases in forest and woodland
      extent and density because of anxiety about wild animals causing harm to crops
      and even humans, and the loss of an agricultural identity to livelihoods and the
      landscape.

PMID- 24918943
TI  - How do earthworms, soil texture and plant composition affect infiltration along
      an experimental plant diversity gradient in grassland?
AB  - BACKGROUND: Infiltration is a key process in determining the water balance, but
      so far effects of earthworms, soil texture, plant species diversity and their
      interaction on infiltration capacity have not been studied. METHODOLOGY/PRINCIPAL
      FINDINGS: We measured infiltration capacity in subplots with ambient and reduced
      earthworm density nested in plots of different plant species (1, 4, and 16
      species) and plant functional group richness and composition (1 to 4 groups;
      legumes, grasses, small herbs, tall herbs). In summer, earthworm presence
      significantly increased infiltration, whereas in fall effects of grasses and
      legumes on infiltration were due to plant-mediated changes in earthworm biomass.
      Effects of grasses and legumes on infiltration even reversed effects of texture.
      We propose two pathways: (i) direct, probably by modifying the pore spectrum and
      (ii) indirect, by enhancing or suppressing earthworm biomass, which in turn
      influenced infiltration capacity due to change in burrowing activity of
      earthworms. CONCLUSIONS/SIGNIFICANCE: Overall, the results suggest that spatial
      and temporal variations in soil hydraulic properties can be explained by biotic
      processes, especially the presence of certain plant functional groups affecting
      earthworm biomass, while soil texture had no significant effect. Therefore biotic
      parameters should be taken into account in hydrological applications.

PMID- 24918944
TI  - PIK3CA and TP53 gene mutations in human breast cancer tumors frequently detected
      by ion torrent DNA sequencing.
AB  - Breast cancer is the most common malignancy and the leading cause of cancer
      deaths in women worldwide. While specific genetic mutations have been linked to 5
      10% of breast cancer cases, other environmental and epigenetic factors influence
      the development and progression of the cancer. Since unique mutations patterns
      have been observed in individual cancer samples, identification and
      characterization of the distinctive breast cancer molecular profile is needed to
      develop more effective target therapies. Until recently, identifying genetic
      cancer mutations via personalized DNA sequencing was impractical and expensive.
      The recent technological advancements in next-generation DNA sequencing, such as
      the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing
      cost and time effective with more reliable results. Using the Ion Torrent
      Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to
      identify genetic mutations in 105 human breast cancer samples. The sequencing
      analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast
      cancer samples of various histologic types. Thus, this study demonstrates the
      necessity of sequencing individual human cancers in order to develop personalized
      drugs or combination therapies to effectively target individual, breast cancer
      specific mutations. 

PMID- 24918946
TI  - National trends in burn and inhalation injury in burn patients: results of
      analysis of the nationwide inpatient sample database.
AB  - The aim of this study was describe national trends in prevalence, demographics,
      hospital length of stay (LOS), hospital charges, and mortality for burn patients
      with and without inhalational injury and to compare to the National Burn
      Repository. Burns and inhalation injury cause considerable mortality and
      morbidity in the United States. There remains insufficient reporting of the
      demographics and outcomes surrounding such injuries. The National Inpatient
      Sample database, the nation's largest all-payer inpatient care data repository,
      was utilized to select 506,628 admissions for burns from 1988 to 2008 based on
      ICD-9-CM recording. The data were stratified based on the extent of injury
      (%TBSA) and presence or absence of inhalational injury. Inhalation injury was
      observed in only 2.2% of burns with <20% TBSA but 14% of burns with 80 to 99%
      TBSA. Burn patients with inhalation injury were more likely to expire in-hospital
      compared to those without (odds ratio, 3.6; 95% confidence interval, 2.7-5.0; P <
      .001). Other factors associated with higher mortality were African-American race,
      female sex, and urban practice setting. Patients treated at rural facilities and
      patients with hyperglycemia had lower mortality rates. Each increase in percent
      of TBSA of burns increased LOS by 2.5%. Patients with burns covering 50 to 59% of
      TBSA had the longest hospital stay at a median of 24 days (range, 17-55). The
      median in-hospital charge for a burn patient with inhalation injury was
      US$32,070, compared to US$17,600 for those without. Overall, patients who expired
      from burn injury accrued higher in-hospital charges (median, US$50,690 vs
      US$17,510). Geographically, California and New Jersey were the states with the
      highest charges, whereas Vermont and Maryland were states with the lowest
      charges. The study analysis provides a broad sampling of nationwide demographics,
      LOS, and in-hospital charges for patients with burns and inhalation injury. 

PMID- 24918945
TI  - Predictors of insulin resistance in pediatric burn injury survivors 24 to 36
      months postburn.
AB  - Burn injury is a dramatic event with acute and chronic consequences including
      insulin resistance. However, factors associated with insulin resistance have not
      been previously investigated. The purpose of this study was to identify factors
      associated with long-term insulin resistance in pediatric burn injury survivors.
      The study sample consisted of 61 pediatric burn injury survivors 24 to 36 months
      after the burn injury, who underwent an oral glucose tolerance test. To assess
      insulin resistance, the authors calculated the area under the curve for glucose
      and insulin. The diagnostic criteria of the American Diabetes Association were
      used to define individuals with impaired glucose metabolism. Additional data
      collected include body composition, anthropometric measurements, burn
      characteristics, and demographic information. The data were analyzed using
      multivariate linear regression analysis. Approximately 12% of the patients met
      the criteria for impaired glucose metabolism. After adjusting for possible
      confounders, burn size, age, and body fat percentage were associated with the
      area under the curve for glucose (P < .05 for all). Time postburn and lean mass
      were inversely associated with the area under the curve for glucose (P < .05 for
      both). Similarly, older age predicted higher insulin area under the curve. The
      results indicate that a significant proportion of pediatric injury survivors
      suffer from glucose abnormalities 24 to 36 months postburn. Burn size, time
      postburn, age, lean mass, and adiposity are significant predictors of insulin
      resistance in pediatric burn injury survivors. Clinical evaluation and screening
      for abnormal glucose metabolism should be emphasized in patients with large
      burns, older age, and survivors with high body fat. 

PMID- 24918947
TI  - A mobile app for measuring the surface area of a burn in three dimensions:
      comparison to the Lund and Browder assessment.
AB  - The aim of this study was to compare the ease and accuracy of measuring the
      surface area of a severe burn through the use of a mobile software application
      (BurnMed) to the traditional method of assessment, the Lund and Browder chart.
      BurnMed calculates the surface area of a burn by enabling the user to first
      manipulate a three-dimensional model on a mobile device and then by touching the
      model at the locations representing the patient's injury. The surface area of the
      burn is calculated in real time. Using a cohort of 18 first-year medical students
      with no experience in burn care, the surface area of a simulated burn on a
      mannequin was made using BurnMed and compared to estimates derived from the Lund
      and Browder chart. At the completion of this study, students were asked to
      complete a questionnaire designed to assess the ease of use of BurnMed. Users
      were able to easily and accurately measure the surface area of a simulated burn
      using the BurnMed application. In addition, there was less variability in surface
      area measurements with the application compared to the results obtained using the
      Lund and Browder chart. Users also reported that BurnMed was easier to use than
      the Lund and Browder chart. A software application, BurnMed, has been developed
      for a mobile device that easily and accurately determines the surface area of a
      burn. This system uses a three-dimensional model that can be rotated, enlarged,
      and transposed by the health care provider to easily determine the extent of a
      burn. Results show that the variability of measurements using BurnMed is lower
      than the measurements obtained using the Lund and Browder chart. BurnMed is
      available at no charge in the AppleTM Store. 

PMID- 24918948
TI  - Clinical outcomes from a foam wedge splinting program for axillary contracture
      prevention in the intensive care unit.
AB  - Preventing scar contracture after burn injury is a critical goal during recovery.
      Although the need for intervention is well-understood, data on specific
      techniques are limited. The study's objective is to provide data for the use of a
      foam abduction wedge in terms of safety, effectiveness, and patient and caregiver
      satisfaction through a prospective, single-arm trial. All patients presenting
      with a burn injury that required grafting in the axillary region and placed them
      at risk for shoulder joint contracture were offered inclusion. Patient outcomes
      were recorded for the duration of their burn intensive care unit admission. Ten
      subjects completed the protocol with a mean duration of wedge use of 41.5 +/-
      32.5 days. At discharge, the mean shoulder abduction was 132 degrees  +/- 38
      degrees  on the left and 118 degrees  +/- 22 degrees  on the right. The mean
      shoulder flexion was 132 degrees  +/- 31 degrees  on the left and 123 degrees  +/
      29 degrees  on the right. As much as 90% of the subjects had greater than 90
      degrees  of shoulder abduction and flexion at discharge. There were no
      observations of worsening burn injury wounds, graft failure, or new pressure
      related wounds. One patient was found to have an upper-extremity peripheral nerve
      injury that was not clearly associated with the splint. Patient and nursing
      surveys indicated areas of satisfaction as well as areas for potential
      improvement. This study illustrates the anticipated clinical outcomes and care
      issues associated with the use of a specific contracture prevention method used
      in the burn intensive care unit setting as well as identifying areas for future
      research. 

PMID- 24918950
TI  - Dental age assessment for different climatic regions.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of several aspects of
      climate, such as temperature and altitude, on dental maturation. MATERIALS AND
      METHODS: The total sample consisted of 944 panoramic radiographs (473 Turkish
      children from Central Anatolia [228 girls and 245 boys] and 471 Turkish children
      from Eastern Anatolia [222 girls and 249 boys]). The children aged between 7.0
      and 14.9 years. The radiographs were randomly selected from 2 cities in Turkey,
      Kayseri and Erzurum. Independent t tests and paired t tests were performed to
      compare sex, location, and age to determine the relationships between tooth
      developments. RESULTS: The Central Anatolian children were approximately 0.2 to
      3.0 years more advanced in dental maturity than the Eastern Anatolian subjects.
      CONCLUSIONS: The development standards proposed by Demirjian are affected by
      climatic factors. However, further research and detailed information to gather
      data are needed.

PMID- 24918949
TI  - The role of seizure disorders in burn injury and outcome in Sub-Saharan Africa.
AB  - Patients with epilepsy have higher incidence and severity of burn injury. Few
      studies describe the association between epilepsy and burns in low-income
      settings, where epilepsy burden is highest. The authors compared patients with
      and without seizure disorder in a burn unit in Lilongwe, Malawi. The authors
      conducted a retrospective study of patients admitted to the Kamuzu Central
      Hospital burn ward from July 2011 to December 2012. Descriptive analysis of
      patient characteristics and unadjusted and adjusted analyses of risk factors for
      mortality were conducted for patients with and without seizure disorder.
      Prevalence of seizure disorder was 10.7% in the study population. Adults with
      burns were more likely to have seizure disorder than children. Flame injury was
      most common in patients with seizure disorder, whereas scalds predominated among
      patients without seizure disorder. Whereas mortality did not differ between the
      groups, mean length of stay was longer for patients with seizure disorder, 42.1
      days vs 21.6 days. Seizure disorder continues to be a significant risk factor for
      burn injury in adults in Malawi. Efforts to mitigate epilepsy will likely lead to
      significant decreases in burns among adults in Sub-Saharan Africa and must be
      included in an overall burn prevention strategy in our environment. 

PMID- 24918951
TI  - Genetic identification by using short tandem repeats analysis in a case of
      suicide by self-incineration: a case report.
AB  - Suicide by self-incineration is an uncommon method of suicide in the western
      world in contrast with Asian countries, where this type of suicide is more
      common. If there is a lack of witnesses, genetic analysis for identification is
      mandatory, especially when anthropologic or dental identification is barely
      significant.The authors report a case of self-incineration of a 55-year-old white
      man, which occurred near Siena, Tuscany, Italy.The recovered bones were
      classified according to the Crow-Glassman scale and assigned to category 5 (the
      highest extent of combustion according to this scale). Therefore, because of the
      extent of the bone damage, analyzing the residual soft tissue around the pelvic
      bones was the only way to reach a genetic identification.The authors report this
      case to emphasize that even if the highest level of burn injury to human body is
      reached, an accurate analysis of the findings may lead to a genetic
      identification. In these cases, an efficient cooperation among police, fire
      experts, and forensics is necessary, especially because it is the only way to
      determine if the modality of death was accidental, suicidal, or homicidal. 

PMID- 24918952
TI  - Acute aortic dissection with carotid and coronary malperfusion: from imaging to
      pathology.
AB  - Postmortem imaging, including postmortem computed tomography angiography, has
      become an integral tool in forensic investigation in recent years. A relatively
      new technique, multiphase postmortem computed tomography angiography, allows
      detailed visualization of the vascular system and makes it possible to evaluate
      the dynamic perfusion of aortic branches, including the coronary arteries. Here,
      we report a case of aortic dissection involving the ascending aorta (type A) with
      coronary and carotid malperfusion. This case illustrates the complementary use of
      many of the diagnostic tools that are now available in forensic practice, from
      imaging to conventional autopsy to pathologic techniques such as
      immunohistochemistry. 

PMID- 24918953
TI  - Bone marrow embolism to the lung in electrocution: two case reports.
AB  - Bone marrow embolism in electrocution was first described in the literature by
      Rappaport et al (Am J Pathol. 1951;27(3):407-433) in 1951. Two case studies
      demonstrating this phenomenon are reported here, one involving high-voltage
      exposure with associated skeletal injuries and the other involving domestic
      current and without evidence of skeletal injury. Both cases demonstrated bone
      marrow embolism on histologic examination of the lungs. The purposes of this
      article are to reiterate the existence of this unusual phenomenon and to consider
      possible pathogenetic mechanisms. 

PMID- 24918954
TI  - Allergy in extremis: a case of sudden unexpected death due to an allergy
      associated disease.
AB  - Allergy-associated diseases have a multitude of confirmed or suspected etiologies
      and associations affecting organs and organ systems. The hyper-reactivity of the
      immune system in which the eosinophils are prominent plays a central role in
      organ-specific and systemic effects in these diseases. Patients may be plagued
      with nonspecific, episodic, or progressive signs and symptoms. Patients may also
      exhibit signs and symptoms that mimic more common conditions. Recognition of
      certain patterns of clinical signs and symptoms may lead to definitive clinical
      diagnosis and effective treatment, particularly of less common but potentially
      lethal disease entities. The lack of clinical recognition of these patterns,
      whether due to "red herring" historical information, lack of sign/symptom
      specificity, clinical presentation at early stage, or unfamiliarity with the
      constellation of disease presentation, may delay or preclude diagnosis and
      treatment. The forensic pathologist must also have an awareness of varied
      clinical presentations of diseases because these can provide us with direction
      toward the ultimate determination of cause and manner of death.The importance and
      contribution of the practice of forensic pathology are highlighted in the
      instance of sudden and unexpected death, whereby the previously unrecognized or
      unconfirmed disease entity that leads to the death is revealed via analysis of
      scene information, autopsy performance, and review of medical history and history
      of the most recent illness. Through this comprehensive approach, a greater
      understanding of the extent and potential lethality of disease with reiteration
      of the importance of early clinical diagnosis and treatment is reinforced. This
      benefits the medical community involved in diagnosis and treatment, clinicians
      and pathologists alike, with the ultimate goal of reduction of morbidity and
      mortality.Reported is a case of sudden unexpected death with historical, gross,
      and microscopic findings consistent with a multisystem, inflammatory, allergic
      disease entity. 

PMID- 24918955
TI  - Big marijuana--lessons from big tobacco.

PMID- 24918957
TI  - Metal-induced conformational changes of human metallothionein-2A: a combined
      theoretical and experimental study of metal-free and partially metalated
      intermediates.
AB  - Electrospray ionization ion mobility mass spectrometry (ESI IM-MS) and molecular
      dynamics (MD) simulations reveal new insights into metal-induced conformational
      changes and the mechanism for metalation of human metallothionein-2A (MT), an
      intrinsically disordered protein. ESI of solutions containing apoMT yields
      multiple charge states of apoMT; following addition of Cd(2+) to the solution,
      ESI yields a range of CdiMT (i = 1-7) product ions (see Chen et al. Anal. Chem.
      2013, 85, 7826-33). Ion mobility arrival-time distributions (ATDs) for the CdiMT
      (i = 0-7) ions reveal a diverse population of ion conformations. The ion mobility
      data clearly show that the conformational diversity for apoMT and partially
      metalated ions converges toward ordered, compact conformations as the number of
      bound Cd(2+) ions increase. MD simulations provide additional information on
      conformation candidates of CdiMT (i = 0-7) that supports the convergence of
      distinct conformational populations upon metal binding. Integrating the IM-MS and
      MD data provides a global view that shows stepwise conformational transition of
      an ensemble as a function of metal ion bound. ApoMT is comprised of a wide range
      of conformational states that populate between globular-like compact and coil
      rich extended conformations. During the initial stepwise metal addition (number
      of metal ions bound i = 1-3), the metal ions bind to different sites to yield
      distinct conformations, whereas for i > 4, the conformational changes appear to
      be domain-specific, attributed to different degrees of disorder of the beta
      domain; the beta domain becomes more ordered as additional metal ions are added,
      promoting convergences to the dumbbell-shaped conformation. 

PMID- 24918958
TI  - Black-blood multicontrast imaging of carotid arteries with DANTE-prepared 2D and
      3D MR imaging.
AB  - PURPOSE: To prospectively compare the black-blood ( BB black blood ) imaging
      efficiency of a delay alternating with nutation for tailored excitation ( DANTE
      delay alternating with nutation for tailored excitation ) preparation module with
      conventional double inversion-recovery ( DIR double inversion recovery ) and
      motion-sensitive driven equilibrium ( MSDE motion-sensitive driven equilibrium )
      preparation modules and to introduce a new three-dimensional ( 3D three
      dimensional ) T1-weighted magnetic resonance (MR) imaging sequence. MATERIALS AND
      METHODS: Carotid artery wall imaging was performed in 10 healthy volunteers and
      15 patients in accordance with an institutional review board-approved protocol.
      Two-dimensional ( 2D two-dimensional ) turbo spin-echo ( TSE turbo spin echo )
      and 3D three-dimensional fast low-angle shot ( FLASH fast low-angle shot )
      sequences served as readout modules. DANTE delay alternating with nutation for
      tailored excitation -prepared T1-, T2-, and proton density-weighted 2D two
      dimensional TSE turbo spin echo images, as well as T1-weighted 3D three
      dimensional DANTE delay alternating with nutation for tailored excitation 
      prepared FLASH fast low-angle shot (hereafter, 3D three-dimensional DASH DANTE
      prepared FLASH ) images, were acquired in the region of the carotid artery
      bifurcation. For comparison, 2D two-dimensional DIR double inversion recovery 
      prepared, 2D two-dimensional MSDE motion-sensitive driven equilibrium -prepared
      multicontrast TSE turbo spin echo , and 3D three-dimensional MSDE motion
      sensitive driven equilibrium -prepared FLASH fast low-angle shot (hereafter, 3D
      three-dimensional MERGE MSDE-prepared FLASH ) MR images were also acquired. The
      effective contrast-to-noise ratio ( CNReff effective contrast-to-noise ratio )
      per unit time was calculated for all sequences. Paired t tests were performed to
      test within-group differences in vessel wall CNReff effective contrast-to-noise
      ratio . RESULTS: The CNReff effective contrast-to-noise ratio of DANTE delay
      alternating with nutation for tailored excitation -prepared T1-, T2-, and proton
      density-weighted sequences was 27.3, 14.7, and 25.7 mm(-1)min(-1/2),
      respectively; this represented an improvement of approximately 25%-100% (P < .05)
      when compared with the CNReff effective contrast-to-noise ratio attained with
      existing methods. The 3D three-dimensional DASH DANTE-prepared FLASH technique
      proved to be a fast (<2 seconds per section) and high-spatial-resolution (0.6 mm
      isotropic) BB black blood technique with higher (75%-100% improvement, P < .001)
      signal-to-noise ratio efficiency than the 3D three-dimensional MERGE MSDE
      prepared FLASH technique. CONCLUSION: The DANTE delay alternating with nutation
      for tailored excitation -prepared multicontrast 2D two-dimensional BB black blood
      technique is a promising new tool for MR imaging of carotid artery walls.
      Additionally, the 3D three-dimensional DASH DANTE-prepared FLASH sequence enables
      3D three-dimensional high-spatial-resolution fast T1-weighted imaging of carotid
      artery walls. (c)RSNA, 2014 Online supplemental material is available for this
      article .

PMID- 24918959
TI  - Adenomatous neoplasia: postsurgical incidence after normal preoperative CT
      colonography findings in the colon proximal to an occlusive cancer.
AB  - PURPOSE: To determine the postoperative incidence of adenomatous neoplasia in the
      colon proximal to an occlusive colorectal cancer where preoperative computed
      tomographic (CT) colonography findings were normal. MATERIALS AND METHODS:
      Institutional review board approval, with a waiver of informed consent, was
      obtained. This observational study included patients with occlusive colorectal
      cancer who underwent preoperative CT colonography between April 2007 and March
      2010 that revealed normal findings (ie, no lesions >= 6 mm) in the proximal colon
      and who underwent postoperative colonoscopy. The primary outcome was
      postoperative colonoscopic discovery of clinically relevant lesions (ie,
      nondiminutive [>= 6 mm] adenomas, advanced adenomas, or cancers) in the proximal
      colon. The cumulative incidence of clinically relevant lesions in preoperatively
      normal proximal colon over the postsurgical follow-up time was analyzed by using
      the Kaplan-Meier method. RESULTS: The final cohort included 204 patients (102 men
      and 102 women; mean age, 57.3 years +/- 11.3 [standard deviation]). At a total of
      435 postoperative colonoscopies performed over a median follow-up of 29 months
      (range, 1-74 months), clinically relevant lesions were detected in the proximal
      colon in 30 patients: Nonadvanced adenomas were detected in 23 patients, and
      advanced adenomas were detected in seven patients. The cumulative incidence of
      clinically relevant adenomatous lesions in the preoperatively normal proximal
      colon 12 and 18 months after preoperative CT colonography was 8.1% (95%
      confidence interval [CI]: 3.9%, 12.2%) and 9.6% (95% CI: 5%, 14%), respectively.
      Clinically relevant adenomatous lesions found in the proximal colon within 18
      months of preoperative CT colonography were nonadvanced adenomas in 10 of 15
      patients. CONCLUSION: When the portion of the colon proximal to an occlusive
      cancer is devoid of nondiminutive lesions at preoperative CT colonography,
      colonoscopy of the proximal colon following cancer resection rarely finds
      clinically relevant lesions and is unlikely to reveal any lesions requiring
      immediate removal until routine 1-year postsurgical follow-up. Online
      supplemental material is available for this article .

PMID- 24918960
TI  - Delayed ischemic stroke after stent-assisted coil placement in cerebral aneurysm:
      characteristics and optimal duration of preventative dual antiplatelet therapy.
AB  - PURPOSE: To evaluate characteristics of delayed ischemic stroke after stent
      assisted coil placement in cerebral aneurysms and to determine the optimal
      duration of dual antiplatelet therapy for its prevention. MATERIALS AND METHODS:
      This retrospective study was approved by the institutional review board, and the
      requirement to obtain written informed consent was waived. Of 1579 patients with
      1661 aneurysms, 395 patients (25.0%) with 403 aneurysms (24.3%) treated with
      stent-assisted coil placement were included and assigned to groups stratified as
      early (126 patients [31.9%]; 3 months of coil placement), midterm (160 patients
      [40.5%]; 6 months), or late (109 patients [27.6%]; >= 9 months), according to the
      time points of switching dual antiplatelet therapy to monotherapy from coil
      placement. Cumulative rates of delayed ischemic stroke in each group were
      calculated by using Kaplan-Meier estimates that were compared with log-rank
      tests. Risk factors of delayed ischemic stroke were identified by using Cox
      proportional hazard analysis. RESULTS: Delayed ischemic stroke occurred in 3.5%
      of all cases (embolism, 3.0%; thrombotic occlusion, 0.5%) within 2 months
      following the switch. Late switch yielded no delayed ischemic stroke, unlike
      early (seven of 126 patients [5.6%]; P = .013) or midterm (seven of 160 patients
      [4.4%]; P = .028) switch. Incomplete occlusion (hazard ratio, 6.68 [95%
      confidence interval: 1.490, 29.900]) was identified as a risk factor. CONCLUSION:
      Delayed ischemic stroke after stent-assisted coil placement is caused by embolism
      from or thrombotic occlusion of stent-containing vessels after switching from
      dual antiplatelet therapy to monotherapy. The stent-containing vessel with
      incomplete aneurysm occlusion presents as a long-term thromboembolic source.
      Therefore, dual antiplatelet therapy for more than 9 months and late switch to
      monotherapy are recommended for its prevention.

PMID- 24918961
TI  - Experimental estimation of the efficacy of the FLOTAC basic technique.
AB  - The FLOTAC technique is a quantitative coproscopic method for the diagnosis of
      parasitic infection that is based on the centrifugation of a fecal sample to
      levitate helminth eggs with a flotation solution in a proprietary apparatus.
      Determination of the efficacy of the FLOTAC method and multiplication factors for
      calculation of the number of Toxocara, Trichuris, and Ascaris eggs in 1 g of
      feces on the basis of the number of detected eggs is presented. An investigation
      was conducted using feces samples enriched with a known number of parasite eggs:
      3, 15, 50, or 100 parasite eggs of 3 nematode genera (Toxocara, Trichuris, and
      Ascaris) per 1 g (EPG) of feces. In addition, 80 samples of dog feces were
      prepared consisting of 20 repetitions for each level of contamination. The
      samples were analyzed using the FLOTAC basic technique. The limit of detection
      was calculated as the lowest level of egg content at which at least 50% of
      repetitions were positive. Multiplication factors for estimating the true number
      of parasite eggs in the samples were derived from regression coefficients that
      illustrated the linear relationship between the number of detected eggs and the
      number of eggs added to the sample. The percentages of recovered eggs for 1
      chamber and for the whole apparatus ranged from 11.67 to 21.90% and from 21.33 to
      40.10%, respectively, depending on dose enrichment and genus of parasite. The
      limit of detection calculated for the whole FLOTAC device was 3 EPG and was 15
      EPG for 1 chamber for each of the 3 parasite genera. The limit of quantification
      calculated for whole FLOTAC was 15 EPG for each of 3 kinds of eggs. For 1
      chamber, the limit of quantification was 15 EPG for Ascaris and Toxocara eggs and
      50 EPG for Trichuris eggs. Multiplication factors for calculation of the number
      of eggs in 1 g of feces calculated for whole FLOTAC were 3 (for Toxocara and
      Ascaris eggs) and 4 (for Trichuris eggs). Experimentally calculated parameters of
      the method differ significantly from the theoretical assumptions of the authors
      of the FLOTAC technique and can significantly affect the reliability of the
      results. This does not alter the fact that the FLOTAC technique is the most
      effective parasitological quantitative method, which can be used to detect
      parasitic forms in feces. However, the results of our study emphasized the need
      for validation of the method before using it in the laboratory. 

PMID- 24918962
TI  - Does the use of preoperative antiglaucoma medications influence trabeculectomy
      success?
AB  - PURPOSE: To investigate the influence of preoperative antiglaucoma medications on
      trabeculectomy outcome. METHODS: Two hundred fifteen eyes, which underwent
      primary trabeculectomy, were retrospectively analyzed. The average follow-up was
      39.8+/-30.3 months. The only cases of primary open-angle glaucoma, with or
      without pseudoexfoliation (PXF), were included. "Complete success" was defined as
      intraocular pressure (IOP) <18 mmHg without glaucoma medications, whereas
      relative success was defined as the same IOP target with medications. The
      influence of the preoperatively used glaucoma medications on surgical success was
      analyzed by univariate Pearson correlation and multivariate (ordinal) regression
      analysis. RESULTS: There were 118 male (54.9%) and 97 female (45.1%) patients
      with a mean age of 66.9+/-9.3 years. PXF glaucoma (PXFG) was present in 93 eyes
      (43.3%). In 33 patients (15.3%), diabetes mellitus (DM) was present. Complete
      success was achieved in 116 eyes (54%), relative success in 81 eyes (37.6%), and
      failure in 18 eyes (8.4%). Neither the total number nor the duration of glaucoma
      medications used before trabeculectomy was found to have any statistically
      significant influence on surgical success. In statistical analysis, a combination
      of topical beta-blocker and carbonic anhydrase inhibitor (BB+CAI) used before
      surgery was found to be associated with statistically better outcome, whereas the
      preoperative use of topical beta-blockers alone could have a negative influence
      on success. PXF was shown to be independently associated with trabeculectomy
      outcome on multivariate regression analysis. CONCLUSION: The glaucoma medications
      used preoperatively were not found to have any statistically significant negative
      influence on the trabeculectomy outcome and use of the combined BB+CAI
      preparation could have a positive influence, whereas the use of topical beta
      blockers alone could have a negative influence on success, although not
      statistically significant. The presence of PXF was independently associated with
      a better surgical outcome.

PMID- 24918963
TI  - Perceptions of benzodiazepine dependence among women age 65 and older.
AB  - A phenomenological study explored whether older women who are chronic
      benzodiazepine users identified themselves as dependent, how dependence was
      perceived, and how meanings and understandings shaped experiences of
      benzodiazepine use. Self-reported benzodiazepine dependence was associated with
      being unable to reduce use or a desire to discontinue use and reliance on
      benzodiazepines to remain comfortable and able to handle daily life. Themes
      included: (a) benzodiazepine dependence is similar to dependence to diabetes or
      blood pressure medications; (b) dependence is distinctive from addiction/abuse;
      (c) addiction/abuse is perceived as worse than dependence; and (d) concerns of
      addiction/abuse result in low-dose benzodiazepine use.

PMID- 24918965
TI  - Outcome predictors of Internet-based brief sex therapy for sexual dysfunctions in
      heterosexual men.
AB  - The authors investigated whether baseline and therapy process characteristics of
      82 heterosexual men participating in an Internet-based sex therapy study predict
      posttreatment sexual functioning. Problem severity, baseline sexual desire and
      baseline sexual satisfaction, but also partner problems and quality of the
      therapeutic relationship are predictive for sexual functioning and sexual
      satisfaction after finishing Internet-based sex therapy. The obtained outcome
      predictors could benefit men with sexual dysfunctions by tailoring online therapy
      programs to their individual characteristics. In addition, therapists should
      realize that clients suffering from erectile dysfunction or premature ejaculation
      in online sex therapy attach great importance to the therapeutic relationship. 

PMID- 24918964
TI  - Interleukin-1 signaling pathway as a therapeutic target in transthyretin
      amyloidosis.
AB  - INTRODUCTION: Inflammation is a key pathological hallmark of several
      neurodegenerative disorders including Alzheimer's disease, Parkinson's disease
      and familial amyloidotic polyneuropathy (FAP). Among all inflammatory cytokines
      associated with FAP, IL-1beta, in particular, has been implicated in playing a
      key pathogenic role. In the present study, we sought to investigate whether
      blocking IL-1beta signaling provides disease-modifying benefits in an FAP mouse
      model. METHODS: We assessed the effect of chronic administration of Anakinra, an
      IL-1 antagonist, on FAP pathogenesis in vivo, using real-time polymerase chain
      reaction (qPCR), semi-quantitative immunohistochemistry (SQ-IHC), western blot
      and nerve morphometric analyses. RESULTS: We found that treatment with Anakinra
      prevents transthyretin (TTR) extracellular deposition in sciatic nerve,
      protecting unmyelinated nerve fibers from aggregate-induced degeneration.
      Moreover, Anakinra administration significantly suppressed IL-1 signaling pathway
      and inhibited apoptosis and nitrative stress. CONCLUSIONS: The present work
      highlights the relevance of the IL-1 signaling pathway in the pathophysiology of
      FAP. Our results bring to light the importance of non-amyloid targets in the
      therapeutic strategies for this disorder. Thus, we propose the use of Anakinra as
      a potential therapeutic agent for TTR-related amyloidosis.

PMID- 24918966
TI  - Significance of population centers as sources of gaseous and dissolved PAHs in
      the lower Great Lakes.
AB  - Polyethylene passive samplers (PEs) were used to measure concentrations of
      gaseous and dissolved polycyclic aromatic hydrocarbons (PAHs) in the air and
      water throughout the lower Great Lakes during summer and fall of 2011.
      Atmospheric Sigma15PAH concentrations ranged from 2.1 ng/m3 in Cape Vincent (NY)
      to 76.4 ng/m3 in downtown Cleveland (OH). Aqueous Sigma18PAH concentrations
      ranged from 2.4 ng/L at an offshore Lake Erie site to 30.4 ng/L in Sheffield Lake
      (OH). Gaseous PAH concentrations correlated strongly with population within 3-40
      km of the sampling site depending on the compound considered, suggesting that
      urban centers are a primary source of gaseous PAHs (except retene) in the lower
      Great Lakes region. The significance of distant population (within 20 km) versus
      local population (within 3 km) increased with subcooled liquid vapor pressure.
      Most dissolved aqueous PAHs did not correlate significantly with population, nor
      were they consistently related to river discharge, wastewater effluents, or
      precipitation. Air-water exchange calculations implied that diffusive exchange
      was a source of phenanthrene to surface waters, while acenaphthylene volatilized
      out of the lakes. Comparison of air-water fluxes with temperature suggested that
      the significance of urban centers as sources of dissolved PAHs via diffusive
      exchange may decrease in warmer months.

PMID- 24918967
TI  - Distinct differences in gene expression patterns in pulmonary arteries of
      patients with chronic obstructive pulmonary disease and idiopathic pulmonary
      fibrosis with pulmonary hypertension.
AB  - RATIONALE: The development of pulmonary hypertension (PH) in patients with
      idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease
      (COPD) is associated with increased morbidity. OBJECTIVES: To elucidate whether
      vascular remodeling in a well-characterized PH-COPD and PH-IPF patient cohort
      results from similar or divergent molecular changes. METHODS: Vascular remodeling
      of donor, PH-COPD, and PH-IPF pulmonary arteries was assessed. Laser capture
      microdissected pulmonary artery profiles in combination with whole genome
      microarrays were performed. MEASUREMENTS AND MAIN RESULTS: Pulmonary arteries
      from patients with COPD and IPF with PH exhibited remodeling of vascular layers
      and reduction of lumen area. Pathway analyses comparing normalized gene
      expression profiles obtained from patients with PH-IPF or PH-COPD revealed the
      retinol and extracellular matrix (ECM) receptor interaction to be the most
      perturbed processes. Within the ECM-receptor pathway, differential regulation of
      5 out of the top 10 results (collagen, type III, alpha-1; tenascin C; collagen,
      type VI, alpha-3; thrombospondin 2; and von Willebrand factor) were verified by
      real-time polymerase chain reaction and immunohistochemical staining.
      CONCLUSIONS: Despite clinical and histologic vascular remodeling in all patients
      with PH-COPD and PH-IPF, differential gene expression pattern was present in
      pulmonary artery profiles. Several genes involved in retinol metabolism and ECM
      receptor interaction enable discrimination of vascular remodeling in PH-IPF or PH
      COPD. This suggests that pulmonary arterial remodeling in PH-COPD and PH-IPF is
      caused by different molecular mechanisms and may require specific therapeutic
      options.

PMID- 24918968
TI  - Antiferromagnetic Slater insulator phase of Na2IrO3.
AB  - Using a hybrid density-functional theory (DFT) calculation including spin-orbit
      coupling (SOC), we predict that the zigzag antiferromagnetic (AFM) ground state
      of the honeycomb layered compound Na2IrO3 opens the observed insulating gap
      through a long-range magnetic order. We show that the effect of SOC and the
      correction of self-interaction error inherent in previous local or semilocal DFT
      calculations play crucial roles in predicting the band gap formation in Na2IrO3.
      It is revealed that the itinerant AFM order with a strong suppression of the Ir
      magnetic moment is attributed to a considerable hybridization of the Ir 5d
      orbitals with the O 2p orbitals. Thus, our results suggest that the insulating
      phase of Na2IrO3 can be represented as a Slater insulator driven by itinerant
      magnetism.

PMID- 24918969
TI  - Association between plasminogen activator inhibitor-1 4G/5G gene polymorphism and
      immunoglobulin A nephropathy susceptibility.
AB  - The association between plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G gene
      polymorphism and immunoglobulin A nephropathy (IgAN) risk is still controversial.
      A meta-analysis was performed to evaluate the association between PAI-1 4 G/5 G
      gene polymorphism and IgAN susceptibility. A predefined literature search and
      selection of eligible relevant studies were performed to collect data from
      electronic database. Four articles were identified for the analysis of
      association between PAI-1 4 G/5 G gene polymorphism and IgAN risk. 4 G allele was
      not associated with IgAN susceptibility in overall populations and in Asians.
      Furthermore, 4 G/4 G and 5 G/5 G genotype were not associated with IgAN for
      overall populations, Asians. In conclusion, PAI-1 4 G/5 G gene polymorphism was
      not associated with IgAN risk in overall populations and in Asians. However, more
      studies should be performed in the future.

PMID- 24918970
TI  - Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the
      chronic kidney disease susceptibility.
AB  - Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with
      the chronic kidney disease (CKD) susceptibility from the published reports are
      still conflicting. This meta-analysis was performed to evaluate the relationship
      between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The
      association studies were identified from PubMed, Cochrane Library and China
      Biological Medicine Database on 1 March 2014, and eligible investigations were
      included and synthesized using meta-analysis method. Nine reports were recruited
      into this meta-analysis for the association of VDR BsmI gene polymorphism with
      CKD susceptibility. In this meta-analysis for overall populations, the BsmI B
      allele BB genotype and bb genotype were not associated with the risk of CKD (B
      allele: OR = 1.12, 95% CI: 0.88-1.44, p = 0.36; BB genotype: OR = 1.15, 95% CI:
      0.81-1.62, p = 0.43; bb genotype: OR = 0.86, 95% CI: 0.61-1.20, p = 0.36).
      Furthermore, VDR BsmI gene polymorphism was not associated with CKD
      susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene
      polymorphism was not associated with CKD susceptibility in overall populations,
      in Asians and in Caucasians. However, more studies should be conducted to confirm
      it.

PMID- 24918971
TI  - Dynamics and rigidity in an intrinsically disordered protein, beta-casein.
AB  - The emergence of intrinsically disordered proteins (IDPs) as a recognized
      structural class has forced the community to confront a new paradigm of
      structure, dynamics, and mechanical properties for proteins. We present novel
      data on the similarities and differences in the dynamics and nanomechanical
      properties of IDPs and other biomacromolecules on the picosecond time scale. An
      IDP, beta-casein (CAS), has been studied in a calcium bound and unbound state
      using neutron and light scattering techniques. We show that CAS partially folds
      and stiffens upon calcium binding, but in the unfolded state, it is softer than
      folded proteins such as green fluorescence protein (GFP). We also see that some
      localized diffusive motions in CAS have a larger amplitude than in GFP at this
      time scale but are still smaller than those observed in tRNA. In spite of these
      differences, CAS dynamics are consistent with the classes of motions seen in
      folded protein on this time scale. 

PMID- 24918972
TI  - Modified brain death model for rats.
AB  - OBJECTIVES: Experimental animal models of brain death that mimic human conditions
      may be useful for investigating novel strategies that increase quality and
      quantity of organs for transplant. MATERIALS AND METHODS: Brain death was induced
      by increasing intracranial pressure by inflating an intracranial placed balloon
      catheter. Brain death was confirmed by flatline electroencephalogram, physical
      signs of apnea, and absence of brain stem reflexes. Donor management was done
      after brain death. Intracranial pressure and physiologic variables were
      continually monitored during 9 hours' follow-up. RESULTS: Ninety percent of brain
      dead animals showed typical signs of brain death such as diabetes insipidus,
      hypertensive, and hypotensive periods. Donor care was performed for 9 hours after
      brain death, and the mean arterial pressure was maintained above 60 mm Hg.
      CONCLUSIONS: We conclude that the rat model of brain death can be performed in a
      standardized, reproducible, and successful way.

PMID- 24918973
TI  - Branched Au nanostructures enriched with a uniform facet: facile synthesis and
      catalytic performances.
AB  - Well-defined noble metal nanocrystals (NMNCs) of a unique morphology yet a
      uniform facet have attracted broad interests. In this regard, those with a highly
      branched architecture have gained particular attention. Most of the currently
      existing branched NMNCs, however, are enclosed by mixed facets. We now report
      that branched Au nanoarchitectures could be facilely fabricated by mixing an
      aqueous solution of KAuCl4, an aqueous dispersion of graphene oxide, and ethanol
      under ambient conditions. Interestingly, unilike the conventional branched NMNCs,
      our unique Au nanostructures are predominately enriched with a uniform facet of
      {111}. Compared to the spherical Au nanostructures exposed with mixed facets, our
      branched nanospecies of a uniform facet display superior catalytic performances
      both for the catalytic reduction of 4-nitrophenol and the electrocatalytic
      oxidation of methanol. Our investigation represents the first example that Au
      nanostructures simultaneously featured with a highly branched architecture and a
      uniform crystal facet could be formulated. Our unique Au nanostructures provide a
      fundamental yet new scientific forum to disclose the correlation between the
      surface atomic arrangement and the catalytic performances of branched NMNCs.

PMID- 24918974
TI  - anti-Diols from alpha-oxyaldehydes: synthesis and stereochemical assignment of
      oxylipins from Dracontium loretense.
AB  - Differentially protected 1,2-diols were synthesized by enantioselective aldehyde
      alpha-oxygenation followed by organomagnesium or -lithium addition. Contrary to a
      previous report, the resultant diols possess an anti configuration. Good
      selectivity was achieved regardless of the hybridization state of the nucleophile
      or the presence or absence of branching. This method was applied to short
      syntheses of all possible stereoisomers of two oxylipins from Dracontium
      loretense with incomplete stereochemical assignments. Spectroscopic comparisons
      between the synthetic and natural oxylipins led to unambiguous assignments. 

PMID- 24918975
TI  - Demonstration of heterogeneous parahydrogen induced polarization using
      hyperpolarized agent migration from dissolved Rh(I) complex to gas phase.
AB  - Parahydrogen-induced polarization (PHIP) was used to demonstrate the concept that
      highly polarized, catalyst-free fluids can be obtained in a catalysis-free regime
      using a chemical reaction with molecular addition of parahydrogen to a water
      soluble Rh(I) complex carrying a payload of compound with unsaturated (C?C)
      bonds. Hydrogenation of norbornadiene leads to formation of norbornene, which is
      eliminated from the Rh(I) complex and, therefore, leaves the aqueous phase and
      becomes a gaseous hyperpolarized molecule. The Rh(I) metal complex resides in the
      original liquid phase, while the product of hydrogen addition is found
      exclusively in the gaseous phase based on the affinity. Hyperpolarized norbornene
      (1)H NMR signals observed in situ were enhanced by a factor of approximately
      10,000 at a static field of 47.5 mT. High-resolution (1)H NMR at a field of 9.4 T
      was used for ex situ detection of hyperpolarized norbornene in the gaseous phase,
      where a signal enhancement factor of approximately 160 was observed. This concept
      of stoichiometric as opposed to purely catalytic use of PHIP-available complexes
      with an unsaturated payload precursor molecule can be extended to other contrast
      agents for both homogeneous and heterogeneous PHIP. The Rh(I) complex was
      employed in aqueous medium suitable for production of hyperpolarized contrast
      agents for biomedical use. Detection of PHIP hyperpolarized gas by low-field NMR
      is demonstrated here for the first time.

PMID- 24918977
TI  - Authors' response.

PMID- 24918978
TI  - Thiopurine metabolite ratios for monitoring therapy in pediatric Crohn disease.
AB  - OBJECTIVES: Thiopurines (azathioprine, 6-mercaptopurine) are a mainstay of
      treatment in Crohn disease (CD). Monitoring intracellular metabolite (6
      thioguanine nucleotides [6-TGN] and 6-methylmercaptopurine [6-MMP]) levels can
      help optimize therapeutic efficacy and minimize potential toxicity. Determination
      of 6-MMP/6-TGN ratios may provide additional useful information, such as the
      identification of individuals with excessive thiopurine methyltransferase
      activity and disadvantageous 6-MMP overproduction. These patients are at
      increased risk of therapeutic failure and hepatotoxicity. The aim of the study
      was to evaluate the correlation of 6-MMP/6-TGN ratios with therapeutic efficacy
      and risk of hepatotoxicity in CD. METHODS: The present study was a single-center
      cross-sectional study including pediatric patients with CD studied prospectively
      with clinical and laboratory assessments along with serial measurements of 6-MMP
      and 6-TGN. Clinical response was determined using established clinical indices.
      RESULTS: The study included 238 pediatric patients with CD with a total of 1648
      evaluation points. The patients were in steroid-free remission at 59.1% of the
      evaluation points. 6-MMP/6-TGN ratios of 4 to 24 were protective against relapse
      (odds ratio [OR] 0.52, 95% confidence interval [CI] -0.39 to 0.69, P = 0.001).
      Hepatotoxicity was associated with high 6-MMP levels (>3919  pmol/8 * 10 red
      blood cell count: OR 7.65, 95% CI 3.7-15.9, P = 0.001) and high 6-MMP/6-TGN
      ratios (>24: OR 5.35, 95% CI -3.43 to 8.43, P = 0.001). CONCLUSIONS: We observed
      significant associations between 6-MMP/6-TGN ratios and clinical response, and
      risk of hepatotoxicity. Our results suggest that determination of thiopurine
      metabolite ratios is a valuable tool for identification of patients at increased
      risk of therapeutic failure and hepatotoxicity.

PMID- 24918976
TI  - Systems analysis of drug-induced receptor tyrosine kinase reprogramming following
      targeted mono- and combination anti-cancer therapy.
AB  - The receptor tyrosine kinases (RTKs) are key drivers of cancer progression and
      targets for drug therapy. A major challenge in anti-RTK treatment is the
      dependence of drug effectiveness on co-expression of multiple RTKs which defines
      resistance to single drug therapy. Reprogramming of the RTK network leading to
      alteration in RTK co-expression in response to drug intervention is a dynamic
      mechanism of acquired resistance to single drug therapy in many cancers. One
      route to overcome this resistance is combination therapy. We describe the results
      of a joint in silico, in vitro, and in vivo investigations on the efficacy of
      trastuzumab, pertuzumab and their combination to target the HER2 receptors.
      Computational modelling revealed that these two drugs alone and in combination
      differentially suppressed RTK network activation depending on RTK co-expression.
      Analyses of mRNA expression in SKOV3 ovarian tumour xenograft showed up
      regulation of HER3 following treatment. Considering this in a computational model
      revealed that HER3 up-regulation reprograms RTK kinetics from HER2
      homodimerisation to HER3/HER2 heterodimerisation. The results showed synergy of
      the trastuzumab and pertuzumab combination treatment of the HER2 overexpressing
      tumour can be due to an independence of the combination effect on HER3/HER2
      composition when it changes due to drug-induced RTK reprogramming. 

PMID- 24918979
TI  - Functional constipation and cow's-milk allergy.

PMID- 24918980
TI  - Appropriateness of emergency department use in pediatric inflammatory bowel
      disease: a quality improvement opportunity.
AB  - OBJECTIVES: We sought to characterize emergency department (ED) encounters for
      pediatric inflammatory bowel disease (IBD) to identify areas for prevention.
      METHODS: Retrospective chart review of 5 consecutive ED encounters at 7 centers
      was performed. RESULTS: Of 35 unique encounters by 32 patients, 3 main factors
      contributed to ED utilization: disease severity or course, day or time of care,
      and physician instruction. Of the ED encounters, approximately one-fifth were
      judged medically unnecessary, and one-half avoidable in a more optimal health
      care system. CONCLUSIONS: ED visits by pediatric patients with IBD may be reduced
      in a more optimal health care system.

PMID- 24918981
TI  - Giant juvenile polyp at the hepatic flexure in a child: is there a need for
      repeat colonoscopy?

PMID- 24918982
TI  - Growth and nutrition in children with trichothiodystrophy.
AB  - OBJECTIVES: Trichothiodystrophy (TTD) is a rare autosomal recessive disorder of
      DNA repair and transcription. Patients have multisystem abnormalities, including
      alterations in growth and development. This report characterizes the growth and
      nutritional status of a cohort of children with TTD. METHODS: Twenty-five
      patients with TTD were evaluated through a natural history study of patients with
      DNA repair diseases at the National Institutes of Health. Mean length of follow
      up was 2.7 years. Retrospective and prospective data on nutritional status and
      height/weight were collected. RESULTS: In general, patients with TTD had
      considerable abnormalities in growth, with a mean height-for-age z score of -2.75
      and a mean weight-for-age z score of -2.60 at baseline clinical evaluation. The
      median weight-for-length at baseline was, however, 50th percentile and indicators
      of adequate nutrition such as serum albumin, hemoglobin, and vitamins D and B12
      were largely within normal limits. Changes in growth parameters as children aged
      were characterized by further separation from standard growth curves (change
      height-for-age z score/year [-0.18 +/- 0.42] and weight-for-age z score/year [
      0.36 +/- 0.51]). Patients who died during follow-up (n = 5) had significantly
      lower standardized height (P = 0.03) and weight (P = 0.006), weight-for-length
      (<0.0001), and higher heart rates (P = 0.02) compared with the remainder of the
      cohort. CONCLUSIONS: Children with TTD have markedly diminished weight-for-age
      and height-for-age relative to reference populations. The cause for this stunted
      growth remains unclear but does not appear to be related to poor nutrient
      absorption or malnutrition.

PMID- 24918983
TI  - Predictors of low weight and tube feedings in children with congenital
      diaphragmatic hernia at 1 year of age.
AB  - OBJECTIVES: Congenital diaphragmatic hernia (CDH) survivors often have
      gastrointestinal disorders, and limited outcome data exist. This study reviewed
      risk factors for low weight and use of feeding tubes after CDH repair at 1 year
      of age. The hypothesis was that patients who required extracorporeal membrane
      oxygenation (ECMO) or with significant pulmonary arterial hypertension (PAH)
      would have lower weight percentiles and more often require tube feedings.
      METHODS: A retrospective chart review of 89 infants with CDH diagnosed in the
      neonatal period was conducted. Statistical analysis was performed using chi test,
      Fisher exact test, and logistic regression. RESULTS: Seventy-two patients (81%)
      survived to 1 year of age. Of these patients, 35% were <5th percentile for weight
      and 18% were receiving tube feedings. Both ECMO and PAH were associated with an
      increased risk for requiring tube feedings at 1 year of age, with respective odds
      ratios of 6.00 (P = 0.01) and 15.75 (P = 0.02); however, neither ECMO nor PAH was
      associated with low weight at 1 year of age. No statistical correlation was found
      between an abnormal pH probe and tube feedings at 1 year of age. CONCLUSIONS:
      Patients with CDH are at increased risk for having a weight <5th percentile at 1
      year of age. A history of ECMO and PAH are independently associated with an
      increased requirement for tube feedings at 1 year of age. Close nutritional
      monitoring and counseling should be considered in all of the patients with CDH,
      particularly those with a history of ECMO or PAH.

PMID- 24918985
TI  - The photochemistry in Photosystem II at 5 K is different in visible and far-red
      light.
AB  - We have earlier shown that all electron transfer reactions in Photosystem II are
      operational up to 800 nm at room temperature [Thapper, A., et al. (2009) Plant
      Cell 21, 2391-2401]. This led us to suggest an alternative charge separation
      pathway for far-red excitation. Here we extend these studies to a very low
      temperature (5 K). Illumination of Photosystem II (PS II) with visible light at 5
      K is known to result in oxidation of almost similar amounts of YZ and the Cyt
      b559/ChlZ/CarD2 pathway. This is reproduced here using laser flashes at 532 nm,
      and we find the partition ratio between the two pathways to be 1:0.8 at 5 K [the
      partition ratio is here defined as (yield of YZ/CaMn4 oxidation):(yield of Cyt
      b559/ChlZ/CarD2 oxidation)]. The result using far-red laser flashes is very
      different. We find partition ratios of 1.8 at 730 nm, 2.7 at 740 nm, and >2.7 at
      750 nm. No photochemistry involving these pathways is observed above 750 nm at
      this temperature. Thus, far-red illumination preferentially oxidizes YZ, while
      the Cyt b559/ChlZ/CarD2 pathway is hardly touched. We propose that the difference
      in the partition ratio between visible and far-red light at 5 K reflects the
      formation of a different first stable charge pair. In visible light, the first
      stable charge pair is considered to be PD1+QA-. In contrast, we propose that the
      electron hole is residing on the ChlD1 molecule after illumination by far-red
      light at 5 K, resulting in the first stable charge pair being ChlD1+QA-. ChlD1 is
      much closer to YZ (11.3 A) than to any component in the Cyt b559/ChlZ/CarD2
      pathway (shortest ChlD1-CarD2 distance of 28.8 A). This would then explain that
      far-red illumination preferentially drives efficient electron transfer from YZ.
      We also discuss mechanisms for accounting for the absorption of the far-red light
      and the existence of hitherto unobserved charge transfer states. The involvement
      of two or more of the porphyrin molecules in the core of the Photosystem II
      reaction center is proposed.

PMID- 24918986
TI  - Fmoc-based synthesis of disulfide-rich cyclic peptides.
AB  - Disulfide-rich cyclic peptides have exciting potential as leads or frameworks in
      drug discovery; however, their use is faced with some synthetic challenges,
      mainly associated with construction of the circular backbone and formation of the
      correct disulfides. Here we describe a simple and efficient Fmoc solid-phase
      peptide synthesis (SPPS)-based method for synthesizing disulfide-rich cyclic
      peptides. This approach involves SPPS on 2-chlorotrityl resin, cyclization of the
      partially protected peptide in solution, cleavage of the side-chain protecting
      groups, and oxidization of cysteines to yield the desired product. We illustrate
      this method with the synthesis of peptides from three different classes of cyclic
      cystine knot motif-containing cyclotides: Mobius (M), trypsin inhibitor (T), and
      bracelet (B). We show that the method is broadly applicable to peptide
      engineering, illustrated by the synthesis of two mutants and three grafted
      analogues of kalata B1. The method reduces the use of highly caustic and toxic
      reagents and is better suited for high-throughput synthesis than previously
      reported methods for producing disulfide-rich cyclic peptides, thus offering
      great potential to facilitate pharmaceutical optimization of these scaffolds. 

PMID- 24918984
TI  - Race affects outcome among infants with intestinal failure.
AB  - OBJECTIVE: Intestinal failure (IF) is a rare, devastating condition associated
      with significant morbidity and mortality. We sought to determine whether ethnic
      and racial differences were associated with patient survival and likelihood of
      receiving an intestinal transplant in a contemporary cohort of children with IF.
      METHODS: This was an analysis of a multicenter cohort study with data collected
      from chart review conducted by the Pediatric Intestinal Failure Consortium. Entry
      criteria included infants <= 12 months receiving parenteral nutrition (PN) for >=
      60 continuous days and studied for at least 2 years. Outcomes included death and
      intestinal transplantation (ITx). Race and ethnicity were recorded as they were
      in the medical record. For purposes of statistical comparisons and regression
      modeling, categories of race were consolidated into "white" and "nonwhite"
      children. RESULTS: Of 272 subjects enrolled, 204 white and 46 nonwhite children
      were available for analysis. The 48-month cumulative incidence probability of
      death without ITx was 0.40 for nonwhite and 0.16 for white children (P < 0.001);
      the cumulative incidence probability of ITx was 0.07 for nonwhite versus 0.31 for
      white children (P = 0.003). The associations between race and outcomes remained
      after accounting for low birth weight, diagnosis, and being seen at a transplant
      center. CONCLUSIONS: Race is associated with death and receiving an ITx in a
      large cohort of children with IF. This study highlights the need to investigate
      reasons for this apparent racial disparity in outcome among children with IF.

PMID- 24918987
TI  - Analysis of species and intra-species associations between the Mycobacterium
      abscessus complex strains using pulsed-field gel electrophoresis (PFGE) and multi
      locus sequence typing (MLST).
AB  - PFGE and MLST showed that the strains of M. massiliense hsp65 II-1 were clearly
      separated from the strains of M. massiliense hsp65 I or II-2 as well as the
      strains of M. abscessus or M. bolletii; thus, M. massiliense hsp6 5II-1 might
      represent an additional subspecies of M. massiliense. 

PMID- 24918988
TI  - An optimized HPLC method for soil fungal biomass determination and its
      application to a detritus manipulation study.
AB  - The goal of this research was to develop modified analytical method for the
      quantitative analysis of ergosterol, which is highly effective marker for fungal
      biomass. We suggest that our optimized method for the determination of ergosterol
      is an effective way to monitor changes in fungal biomass under different
      environmental conditions. 

PMID- 24918989
TI  - Development, optimization and validation of a rapid colorimetric microplate
      bioassay for neomycin sulfate in pharmaceutical drug products.
AB  - Microbiological assays have been used to evaluate antimicrobial activity since
      the discovery of the first antibiotics. Despite their limitations,
      microbiological assays are widely employed to determine antibiotic potency of
      pharmaceutical dosage forms, since they provide a measure of biological activity.
      The aim of this work is to develop, optimize and validate a rapid colorimetric
      microplate bioassay for the potency of neomycin in pharmaceutical drug products.
      Factorial and response surface methodologies were used in the development and
      optimization of the choice of microorganism, culture medium composition, amount
      of inoculum, triphenyltetrazolium chloride (TTC) concentration and neomycin
      concentration. The optimized bioassay method was validated by the assessment of
      linearity (range 3.0 to 5.0MUg/mL, r=0.998 and 0.994 for standard and sample
      curves, respectively), precision (relative standard deviation (RSD) of 2.8% and
      4.0 for repeatability and intermediate precision, respectively), accuracy (mean
      recovery=100.2%) and robustness. Statistical analysis showed equivalency between
      agar diffusion microbiological assay and rapid colorimetric microplate bioassay.
      In addition, microplate bioassay had advantages concerning the sensitivity of
      response, time of incubation, and amount of culture medium and solutions
      required. 

PMID- 24918990
TI  - Building a molecular Listeria monocytogenes database to centralize and share PFGE
      typing data from food, environmental and animal strains throughout Europe.
AB  - The European Union Reference Laboratory (EURL) for Listeria monocytogenes (Lm)
      collaborates with a network of 35 National Reference Laboratories (NRLs)
      throughout Europe. Most of these NRLs are in charge of detecting and typing Lm
      strains from food, environment and animals, which are isolated nationally. The
      past few years EURL activities have enabled NRLs to reinforce typing capabilities
      according to standardised protocols. Consequently the need to exchange typing
      data within the NRL network has emerged. That is why the EURL has recently set up
      a EURL Lm Database (EURL Lm DB). Each NRL contributes data, which is then shared
      within the network. Data include strain-typing-results (PFGE and serotyping) and
      epidemiological information on the strains. This article describes (1) the EURL
      typing activities that led to the creation of the EURL Lm DB, (2) the different
      steps involved in developing the EURL Lm DB, and (3) the usefulness of this
      database for public health. The combined use of this database, with databases on
      human strains, is being integrated into the European surveillance system of Lm
      strains circulating throughout Europe. It should improve the detection of this
      pathogen and provide support for outbreak investigations. 

PMID- 24918992
TI  - Call for awareness of the updated diagnostic criteria and clinical management for
      patients with tuberous sclerosis complex.

PMID- 24918994
TI  - Hereditary polycystic kidney disease: genetic diagnosis and counseling.

PMID- 24918995
TI  - Mueller Weiss syndrome--case report.

PMID- 24918997
TI  - Correlation between body mass index and overactive bladder symptoms in pre
      menopausal women.
AB  - OBJECTIVE: The aim of the study was to establish a correlation between Overactive
      Bladder (OAB) symptoms and Body Mass Index (BMI) in women aged 20-45. METHODS: We
      interviewed 1.050 women aged 20-45 in the area of Campinas, Brazil, to
      investigate the prevalence of overactive bladder symptoms. In this study, we used
      the ICIQ-OAB questionnaire (ICS standard), in its validated portuguese version
      and a specific questionnaire for the demographics, which includes information
      about BMI. RESULTS: Overall, women with BMI >=30 presented a significantly higher
      score than women with a lower BMI (18.5 - 24.9) (p=0.0066). In the analysis of
      individual symptoms, no significant differences were found regarding urinary
      frequency (p=0.5469). Women with BMI >=30 presented more nocturia than women with
      BMI ranging between 18.5 and 24.9 (p=0.0154). Women in the group of BMI 25 - 29.9
      presented more urgency than women with BMI 18.5 - 24.9 (p=0.0278). Significant
      difference was also found regarding urge-incontinence; women with BMI 25 - 29.9
      presented a higher score than women in the group 18.5 - 24.9 (p= 0.0017).
      Analysis was also performed on the visual analogue scale regarding how much each
      symptom bothers the women (quality of life). There were no significant
      differences regarding frequency, nocturia or urgency but urgency incontinence
      bother was significant. Women with BMI 25 - 29.9 were more bothered by
      incontinence than women with BMI 18.5 - 24.9 (p=0.002). CONCLUSION: In
      conclusion, this study reinforces the correlation between BMI and OAB symptoms.
      Obese women present more OAB symptoms than non-obese women.

PMID- 24918996
TI  - Hypertension, pregnancy and weather: is seasonality involved?
AB  - OBJECTIVE: The present study aimed at assessing the association between
      environmental temperature and the relative humidity of the air with frequency of
      hypertensive disorders of pregnancy. METHODS: A prospective and retrospective,
      descriptive, ecological study was held at a teaching maternity in Recife, Brazil.
      Data from all 26.125 pregnant women admitted between 2000 and 2006 were analysed
      and 5.051 had the diagnosis of hypertensive disorder of pregnancy. The incidence
      percentages were calculated monthly per deliveries. Data on mean monthly
      temperature and relative humidity of the air were collected and monthly
      comparisons were conducted. February was chosen as the reference month due to its
      lowest incidence of the disease. The relative chance of hypertensive disorders of
      pregnancy for each other month was estimated by odds ratio and Pearson's
      correlation coefficient was used to calculate the relation between the incidence
      of hypertensive disorders of pregnancy and the mean monthly temperature and
      relative air humidity. RESULTS: February presented the lowest mean monthly
      incidence (9.95%) and August the highest (21.54%). Pearson correlation
      coefficient revealed a higher incidence of hypertensive disorders of pregnancy in
      the cooler months (r= -0.26; p=0.046) and no significant effect of relative air
      humidity (r=0.20; p=0.128). CONCLUSION: The incidence of hypertensive disorders
      of pregnancy may be affected by variations in temperature, increasing during
      cooler periods.

PMID- 24918998
TI  - Diabetes mellitus and impaired glucose tolerance in urban adult population.
AB  - OBJECTIVE: Estimating the prevalence of diabetes mellitus (DM) and impaired
      glucose tolerance (IGT) in the urban population aged between 30 and 69 years in
      the municipality of Campo Grande, state of Mato Grosso do Sul, Brazil. METHODS:
      Population-based cross-sectional study conducted between October/2009 and
      February/2011. The investigation included the determination of fasting glucose
      and participants with blood glucose >= 200 mg/dL were considered diabetic.
      Nondiabetic patients, which showed blood glucose >= 100 mg/dL and < 200 mg/dL,
      underwent an oral glucose tolerance test (OGTT) to investigate whether they had
      DM or IGT. RESULTS: 1.429 individuals participated in this investigation. The
      general prevalence, adjusted for sex and age, were: 12.3% for DM (95%CI: 10.5 to
      13.9%) and 7.1% for IGT (95%CI: 5.7 to 8.4%). There was a higher prevalence of DM
      with increasing age in people with low educational level, family history of
      diabetes, overweight, obesity and central obesity. Among diabetic patients (n =
      195), 25% were unaware they had the disease and were diagnosed through
      investigation. Among patients who already knew they had DM (n = 146), 37% were
      unaware of the potential chronic complications. CONCLUSION: This study confirms
      the increased prevalence of DM in Brazil and emphasizes the need for early
      diagnosis, as well as the importance of strict adherence to medical treatment in
      order to prevent its much feared complications.

PMID- 24918999
TI  - Should fetal growth be a matter of concern in isolated single umbilical artery?
AB  - OBJECTIVE: To examine birth weight in pregnancies with isolated single umbilical
      artery (ISUA). METHODS: Case control study with retrospective review of 131
      singleton pregnancies with isolated single umbilical artery diagnosed before
      birth. Control group consisted of 730 singleton pregnancies recruited
      prospectively, that had histological confirmation of a 3 vessels cord.
      Pregnancies were classified as uncomplicated or high-risk according to the
      presence of diseases that increase the risk of placental insufficiency during
      pregnancy. Mean birth weight and frequency of low birth weight (< 2.500 g), very
      low birth weight (< 1.500 g) and fetal growth restriction below the 5th and 10th
      centiles were compared between groups. RESULTS: Mean birth weight difference
      between ISUA (n=131, 2840+/-701g) and control (n=730, 2.983 +/- 671g) pregnancies
      was 143g (95% CI= 17-269; p=0.04) and birth weight below the 5thcentile was
      significantly more common in ISUA group [28/131 (21.4%) versus 99/730 (13.6%),
      p=0.02]. When only uncomplicated pregnancies were considered in both groups, no
      birth weight differences were observed. Amongst high-risk subgroups, birth weight
      below the 5th centile remained significantly more common in ISUA compared to
      control pregnancies [10/35 (28.6%) versus 53/377 (14.1%), p=0.04]. CONCLUSION:
      Isolated single umbilical artery does not increase the risk of fetal growth
      restriction in uncomplicated singleton pregnancies.

PMID- 24919000
TI  - Oral acetylsalicylic acid and prevalence of actinic keratosis.
AB  - OBJECTIVE: To investigate the influence of a regular oral use of acetylsalicylic
      acid in the prevalence of actinic keratosis. METHODS: A case-control study with
      dermatologic outpatients above 50 years of age assessed between 2009 and 2011.
      Cases were defined as those who had been under regular use of oral
      acetylsalicylic acid for more than six consecutive months. The assessment focused
      on: age, sex, skin-type, tobacco smoking, use of medication, occurrence of
      individual or family skin cancer, and sunscreen and sun exposure habits. Actinic
      keratoses were counted in the medial region of the face and upper limbs. Counts
      were adjusted by co-variables based on a generalized linear model. RESULTS: A
      total of 74 cases and 216 controls were assessed. The median time of
      acetylsalicylic acid use was 36 months. Cases differed from controls as to the
      highest age, highest prevalence of use of angiotensin-converting enzyme
      inhibitors and fewer keratosis on the face and on the upper limbs (p<0.05). The
      multivariate model showed that the use of acetylsalicylic acid was associated to
      lower counts of face actinic keratosis and upper-limb erythematous actinic
      keratosis (p<0.05), regardless of other risk factors. CONCLUSION: The regular use
      of oral acetylsalicylic acid for more than six months was associated to a lower
      prevalence of actinic keratosis, especially facial and erythematous ones.

PMID- 24919001
TI  - Body composition of preschool children and relation to birth weight.
AB  - OBJECTIVE: to evaluate the relationship between body composition of preschool
      children suffering from excess weight and birth weight (BW). METHODS:
      probabilistic sample, by conglomerates, with 17 daycare centers (of a total of
      59) composing a final sample of 479 children. We used Z-score of Body Mass Index
      (zBMI) >= +1 and >= +2, respectively, to identify preschool children with risk of
      overweight and excess weight (overweight or obesity). The arm muscle area (AMA)
      and the arm fat area (AFA) were estimated from measurements of arm circumference,
      triceps skin fold thickness. RESULTS: the prevalence of risk of overweight was
      22.9% (n=110) and excess weight was 9.3% (n=44). The risk of overweight and
      excess weight in children did not show correlation between BW and AFA, but it did
      with adjusted arm muscle area (AMAa) (rp= 0.21; p= 0.0107). The analysis of the
      group with excess weight alone also showed a positive correlation between BW and
      AMAa (rp= 0.42; p= 0.0047). CONCLUSION: among overweight children, lower BW is
      associated with a lower arm muscle area in early preschool age, regardless of the
      fat arm area presented by them.

PMID- 24919002
TI  - Academic autopsies in Brazil--a national survey.
AB  - OBJECTIVE: To investigate the number and rate of academic autopsies, general
      organization, educational and research in Brazilian academic services. METHODS:
      Standardized questionnaires were sent to Brazilian medical schools (n=177) and
      active pathology residency programs (n=53) from March to June 2009. Data were
      collected for years 2003 to 2008. RESULTS: Thirty-two academic services in 11
      Brazilian states answered the survey. Twenty-one (65.6%) perform less than a
      hundred autopsies for natural causes and less than fifty pediatric or fetal
      autopsies/year. Twenty-four (75%) perform less than a hundred adult
      autopsies/year. Many institutions (46.9%) reported a drop in the number of
      autopsies in a six-year period. The total autopsy count and autopsy rate in 2008
      ranged 1-632 (median = 80), and 0-66% (mean = 10.6%), respectively. A steady
      decrease in the total count of autopsies in a pool of 19 institutions was
      observed (p<0.01). Median autopsy rates have fallen from 19.3%, in 2003, to
      10.6%, in 2008 (p=0.07). Significant discrepancies at autopsies led to changes in
      institutional healthcare practice in 37.5% of the services. The low number of
      autopsies was a limiting factor in undergraduate education for 25% of
      respondents. A minimum number of autopsies is required to complete the pathology
      residency program in 34.6% of the services. CONCLUSION: The total number and the
      rate of academic autopsies have decreased in Brazil between 2003 and 2008. The
      number of autopsies and the general organization of academic services must be
      enhanced to improve medical education, research, and the quality control of
      patient care.

PMID- 24919003
TI  - Dynamic compared to rigid fixation in lumbar spine: a systematic review.
AB  - OBJECTIVE: The objective of this review is to reveal the quality of published
      data and the effect size of DPFs compared to rigid fixation in lumbar spine.
      SUMMARY OF BACKGROUND DATA: since 2002, several dynamic pedicle fixation (DPF)
      systems have been developed with the aim to stabilize the spine without the
      undesirable effects of rigid lumbar spine fixation. Nearly ten years later, there
      are several studies on these dynamic systems. METHODS: A systematic review was
      done in MEDLINE/PubMED, Embase, Cochrane Central Register of Randomized Trials
      and Google Scholar to assess the quality of published literature and the
      available studied outcomes in randomized controlled trials of DPF. RESULTS: Only
      three papers described randomized trials studying DPF. One of them focused on
      protection of adjacent level disease provided by DPF. CONCLUSION: It was not
      possible to reveal any evidence for benefits using DPF compared to rigid fixation
      in surgery for lumbar spine.

PMID- 24919004
TI  - Communication between health professionals and patients: review of studies using
      the RIAS (Roter Interaction Analysis System) method.
AB  - OBJECTIVE: Systematic review of studies that investigate the communication
      between patients and health professionals with the application of the RIAS
      methodology. METHODS: Keyword Roter Interaction Analysis System was searched in
      the following bibliographic resources: Academic Search Complete, Current
      Contents, ISI Proceedings, PubMed, Elsevier, SpringerLink, Web of Science, RCAAP,
      Solo and the official RIAS site. Selection period: 2006 to 2011. Studies were
      selected using multicriteria dichotomous analysis and organized according to
      PRISMA. RESULTS: Identification of 1,262 articles (455 unrepeated). 34 articles
      were selected for analysis, distributed by the following health professions:
      family medicine and general practitioners (14), pediatricians (5), nurses (4),
      geneticists (3), carers of patients with AIDS (2), oncologists (2), surgeons (2),
      anesthetists (1) and family planning specialists (1). The RIAS is scarcely used
      and publicized within the scope of healthcare in Portuguese speaking countries.
      DISCUSSION: Main themes studied include the influence of tiredness, anxiety and
      professional burnout on communication and the impact of specific training actions
      on professional activities. The review enabled the identification of the main
      strengths and weaknesses of synchronous and dyadic verbal communication within
      the provision of healthcare. CONCLUSION: Scientific investigation of the
      communication between health professionals and patients using RIAS has produced
      concrete results. An improvement is expected in health outcomes through the
      application of the RIAS.

PMID- 24919005
TI  - Alzheimer's disease and periodontitis--an elusive link.
AB  - Alzheimer's disease is the preeminent cause and commonest form of dementia. It is
      clinically characterized by a progressive descent in the cognitive function,
      which commences with deterioration in memory. The exact etiology and
      pathophysiologic mechanism of Alzheimer's disease is still not fully understood.
      However it is hypothesized that, neuroinflammation plays a critical role in the
      pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient
      inflammatory features, characterized by microglial activation and escalation in
      the levels of pro-inflammatory cytokines in the affected regions. Studies have
      suggested a probable role of systemic infection conducing to inflammatory status
      of the central nervous system. Periodontitis is common oral infection affiliated
      with gram negative, anaerobic bacteria, capable of orchestrating localized and
      systemic infections in the subject. Periodontitis is known to elicit a "low grade
      systemic inflammation" by release of pro-inflammatory cytokines into systemic
      circulation. This review elucidates the possible role of periodontitis in
      exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect
      the onset and progression of Alzheimer's disease. Periodontitis shares the two
      important features of Alzheimer's disease namely oxidative damage and
      inflammation, which are exhibited in the brain pathology of Alzheimer's disease.
      Periodontitis can be treated and hence it is a modifiable risk factor for
      Alzheimer's disease.

PMID- 24919006
TI  - Antiphospholipid syndrome: a clinical and laboratorial challenge.
AB  - Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia
      characterized by the presence of a heterogeneous family of antibodies that bind
      to plasma proteins with affinity for phospholipid surfaces. The two major protein
      targets of antiphospholipid antibodies are prothrombin and beta2-glycoprotein I
      (beta2GPI). APS leads to aprothrombotic state, and it is characterized by the
      occurrence of arterial, venous or microvascular thrombosis or recurrent fetal
      loss. The diagnosis of APS is based on a set of clinical criteria and the
      detection of lupus anticoagulant (LA), anticardiolipin antibodies (ACA) or anti
      beta2GPI in plasma. Although laboratory tests are essential for APS diagnosis,
      these tests have limitations associated with the robustness, reproducibility and
      standardization. The standardization of diagnostic tests for detection of APLAs
      has been a challenge and a variety of results have been obtained using different
      commercial kits and in-house techniques. An increased sensitivity of the ELISA
      kits for detection of ACA effectively has contributed to APS diagnosis. However,
      the lack of specificity associated with a high number of false-positive results
      is a clinical and laboratorial challenge, since such results may lead to mistaken
      clinical decisions, such as prescription of oral anticoagulant, leading to the
      risk of hemorrhaging. Furthermore, clinicians are often unfamiliar with these
      tests and have difficulty interpreting them, requiring interaction between
      clinical and laboratory professionals in order to ensure their correct
      interpretation.

PMID- 24919007
TI  - Off-premise alcohol outlet characteristics and violence.
AB  - BACKGROUND: There is considerable evidence of an association between alcohol
      outlet density and violence. Although prior research reveals the importance of
      specific characteristics of bars on this association and that the relationship
      between bar density and violence may be moderated by these characteristics, there
      are few similar studies of the characteristics of off-premise outlets (e.g.,
      liquor and convenience stores). OBJECTIVES: We examined whether immediate
      environment, business practice, staff, and patron characteristics of off-premise
      alcohol outlets are associated with simple and aggravated assault density.
      METHODS: Cross-sectional design using aggregate data from 65 census block groups
      in a non-metropolitan college town, systematic social observation, and spatial
      modeling techniques. RESULTS: We found limited effects of immediate environment,
      business practice, staff, and patron characteristics on simple assault density
      and no effect on aggravated assault density. Only two out of 17 characteristics
      were associated with simple assault density (i.e., nearby library and male
      patrons). CONCLUSION: This is the first study to examine the association between
      several off-premise alcohol outlet characteristics and assault. Our findings
      suggest that where the off-premise outlets are located, how well the immediate
      environment is maintained, what types of beverages the outlets sell, who visits
      them, and who works there matter little in their association with violence. This
      suggests the importance of outlet density itself as a primary driver of any
      association with violence. Public policies aimed at reducing alcohol outlet
      density or clustering may be useful for reducing violence.

PMID- 24919008
TI  - Is experimental data quality the limiting factor in predicting the aqueous
      solubility of druglike molecules?
AB  - We report the results of testing quantitative structure-property relationships
      (QSPR) that were trained upon the same druglike molecules but two different sets
      of solubility data: (i) data extracted from several different sources from the
      published literature, for which the experimental uncertainty is estimated to be
      0.6-0.7 log S units (referred to mol/L); (ii) data measured by a single accurate
      experimental method (CheqSol), for which experimental uncertainty is typically
      <0.05 log S units. Contrary to what might be expected, the models derived from
      the CheqSol experimental data are not more accurate than those derived from the
      "noisy" literature data. The results suggest that, at the present time, it is the
      deficiency of QSPR methods (algorithms and/or descriptor sets), and not, as is
      commonly quoted, the uncertainty in the experimental measurements, which is the
      limiting factor in accurately predicting aqueous solubility for pharmaceutical
      molecules. 

PMID- 24919009
TI  - Ditopic boronic acid and imine-based naphthalimide fluorescence sensor for
      copper(II).
AB  - Copper ions are essential for many biological processes. However, high
      concentrations of copper can be detrimental to the cell or organism. A novel
      naphthalimide derivative bearing a monoboronic acid group (BNP) was investigated
      as a Cu(2+) selective fluorescent sensor in living cells. This derivative is one
      of the rare examples of reversible fluorescent chemosensors for Cu(2+) which uses
      a boronic acid group for a binding site. Moreover, the adduct BNP-Cu(2+) displays
      a fluorescence enhancement with fructose. The uptake of this novel compound in
      HeLa cancer cells was imaged using confocal fluorescence microscopy techniques
      including two-photon fluorescence lifetime imaging microscopy. 

PMID- 24919010
TI  - Rational construction of strongly coupled metal-metal oxide-graphene
      nanostructure with excellent electrocatalytic activity and durability.
AB  - The interaction within heterogeneous nanostructures can provide a great
      opportunity to radically enhance their electrocatalytic properties and increase
      their activity and durability. Here a rational, simple, and integrated strategy
      is reported to construct uniform and strongly coupled metal-metal oxide-graphene
      nanostructure as an electrocatalyst with high performance. We first simply
      synthesized the interacted SnO2-prGO (protected and reduced graphene oxide)
      hybrid with SnO2 nanoparticles (~4 nm) selectively anchored on the oxygenated
      defects of rGO using an in situ redox and hydrolysis reaction. After the
      deposition of Pt, uniform Pt NPs are found to contact intimately and exclusively
      with the SnO2 phase in the SnO2-prGO hybrid. This constructed nanostructure (Pt
      SnO2-prGO) exhibits significantly improved electrocatalytic activity (2.19-fold)
      and durability (2.08-fold) toward methanol oxidation over that of the state-of
      the-art Pt/C catalyst. The detailed explanation of the strong coupling between
      SnO2 and graphene as well as between Pt and SnO2 is discussed, revealing that
      such a process can be used to immobilize various metal catalysts on metal-oxide
      decorated catalysts for realizing advanced catalytic systems with enhanced
      performance. 

PMID- 24919011
TI  - Characteristics verification of an independently controllable electromagnetic
      spherical motor.
AB  - We have been developing electromagnetic spherical actuators capable of three
      degree-of-freedom rotation. However, these actuators require complex control to
      realize simultaneous triaxial drive, because rotation around one axis interferes
      with rotation around another. In this paper, we propose a new three-degree-of
      freedom actuator where 3-axes rotation can be controlled easily. The basic
      structure and the operating principle of the actuator are described. Then the
      torque characteristics and the dynamic characteristics are computed by employing
      3D-FEM and the effectiveness of this actuator is clarified. Finally, the
      experimental results using the prototype of the actuator are shown to verify the
      dynamic performance. 

PMID- 24919012
TI  - Security enhanced user authentication protocol for wireless sensor networks using
      elliptic curves cryptography.
AB  - Wireless sensor networks (WSNs) consist of sensors, gateways and users. Sensors
      are widely distributed to monitor various conditions, such as temperature, sound,
      speed and pressure but they have limited computational ability and energy. To
      reduce the resource use of sensors and enhance the security of WSNs, various user
      authentication protocols have been proposed. In 2011, Yeh et al. first proposed a
      user authentication protocol based on elliptic curve cryptography (ECC) for WSNs.
      However, it turned out that Yeh et al.'s protocol does not provide mutual
      authentication, perfect forward secrecy, and key agreement between the user and
      sensor. Later in 2013, Shi et al. proposed a new user authentication protocol
      that improves both security and efficiency of Yeh et al.'s protocol. However, Shi
      et al.'s improvement introduces other security weaknesses. In this paper, we show
      that Shi et al.'s improved protocol is vulnerable to session key attack, stolen
      smart card attack, and sensor energy exhausting attack. In addition, we propose a
      new, security-enhanced user authentication protocol using ECC for WSNs. 

PMID- 24919013
TI  - Affine transform to reform pixel coordinates of EOG signals for controlling robot
      manipulators using gaze motions.
AB  - Biosignals will play an important role in building communication between machines
      and humans. One of the types of biosignals that is widely used in neuroscience
      are electrooculography (EOG) signals. An EOG has a linear relationship with eye
      movement displacement. Experiments were performed to construct a gaze motion
      tracking method indicated by robot manipulator movements. Three operators looked
      at 24 target points displayed on a monitor that was 40 cm in front of them. Two
      channels (Ch1 and Ch2) produced EOG signals for every single eye movement. These
      signals were converted to pixel units by using the linear relationship between
      EOG signals and gaze motion distances. The conversion outcomes were actual pixel
      locations. An affine transform method is proposed to determine the shift of
      actual pixels to target pixels. This method consisted of sequences of five
      geometry processes, which are translation-1, rotation, translation-2, shear and
      dilatation. The accuracy was approximately 0.86 degrees  +/- 0.67 degrees  in the
      horizontal direction and 0.54 degrees  +/- 0.34 degrees  in the vertical. This
      system successfully tracked the gaze motions not only in direction, but also in
      distance. Using this system, three operators could operate a robot manipulator to
      point at some targets. This result shows that the method is reliable in building
      communication between humans and machines using EOGs. 

PMID- 24919014
TI  - Joint target tracking, recognition and segmentation for infrared imagery using a
      shape manifold-based level set.
AB  - We propose a new integrated target tracking, recognition and segmentation
      algorithm, called ATR-Seg, for infrared imagery. ATR-Seg is formulated in a
      probabilistic shape-aware level set framework that incorporates a joint view
      identity manifold (JVIM) for target shape modeling. As a shape generative model,
      JVIM features a unified manifold structure in the latent space that is embedded
      with one view-independent identity manifold and infinite identity-dependent view
      manifolds. In the ATR-Seg algorithm, the ATR problem formulated as a sequential
      level-set optimization process over the latent space of JVIM, so that tracking
      and recognition can be jointly optimized via implicit shape matching where target
      segmentation is achieved as a by-product without any pre-processing or feature
      extraction. Experimental results on the recently released SENSIAC ATR database
      demonstrate the advantages and effectiveness of ATR-Seg over two recent ATR
      algorithms that involve explicit shape matching. 

PMID- 24919015
TI  - Fusion of smartphone motion sensors for physical activity recognition.
AB  - For physical activity recognition, smartphone sensors, such as an accelerometer
      and a gyroscope, are being utilized in many research studies. So far,
      particularly, the accelerometer has been extensively studied. In a few recent
      studies, a combination of a gyroscope, a magnetometer (in a supporting role) and
      an accelerometer (in a lead role) has been used with the aim to improve the
      recognition performance. How and when are various motion sensors, which are
      available on a smartphone, best used for better recognition performance, either
      individually or in combination? This is yet to be explored. In order to
      investigate this question, in this paper, we explore how these various motion
      sensors behave in different situations in the activity recognition process. For
      this purpose, we designed a data collection experiment where ten participants
      performed seven different activities carrying smart phones at different
      positions. Based on the analysis of this data set, we show that these sensors,
      except the magnetometer, are each capable of taking the lead roles individually,
      depending on the type of activity being recognized, the body position, the used
      data features and the classification method employed (personalized or
      generalized). We also show that their combination only improves the overall
      recognition performance when their individual performances are not very high, so
      that there is room for performance improvement. We have made our data set and our
      data collection application publicly available, thereby making our experiments
      reproducible. 

PMID- 24919017
TI  - Thermal physical property-based fusion of geostationary meteorological satellite
      visible and infrared channel images.
AB  - Geostationary meteorological satellite infrared (IR) channel data contain
      important spectral information for meteorological research and applications, but
      their spatial resolution is relatively low. The objective of this study is to
      obtain higher-resolution IR images. One common method of increasing resolution
      fuses the IR data with high-resolution visible (VIS) channel data. However, most
      existing image fusion methods focus only on visual performance, and often fail to
      take into account the thermal physical properties of the IR images. As a result,
      spectral distortion occurs frequently. To tackle this problem, we propose a
      thermal physical properties-based correction method for fusing geostationary
      meteorological satellite IR and VIS images. In our two-step process, the high
      resolution structural features of the VIS image are first extracted and
      incorporated into the IR image using regular multi-resolution fusion approach,
      such as the multiwavelet analysis. This step significantly increases the visual
      details in the IR image, but fake thermal information may be included. Next, the
      Stefan-Boltzmann Law is applied to correct the distortion, to retain or recover
      the thermal infrared nature of the fused image. The results of both the
      qualitative and quantitative evaluation demonstrate that the proposed physical
      correction method both improves the spatial resolution and preserves the infrared
      thermal properties. 

PMID- 24919016
TI  - Quorum sensing activity in Pandoraea pnomenusa RB38.
AB  - Strain RB38 was recovered from a former dumping area in Malaysia. MALDI-TOF mass
      spectrometry and genomic analysis identified strain RB-38 as Pandoraea pnomenusa.
      Various biosensors confirmed its quorum sensing properties. High resolution
      triple quadrupole liquid chromatography-mass spectrometry analysis was
      subsequently used to characterize the N-acyl homoserine lactone production
      profile of P. pnomenusa strain RB38, which validated that this isolate produced N
      octanoyl homoserine lactone as a quorum sensing molecule. This is the first
      report of the production of N-octanoyl homoserine lactone by P. pnomenusa strain
      RB38. 

PMID- 24919018
TI  - Application of an electrochemical immunosensor with a MWCNT/PDAA modified
      electrode for detection of serum trypsin.
AB  - OBJECTIVE: To establish an electrochemical immunosensor for the determination of
      serum trypsin levels using a multiwall carbon nanotubes (MWCNTs)-composite
      modified electrode. METHOD: A MWCNT composite coated on the surface of bare gold
      electrodes was used for fixation of an anti-trypsin antibody. The assembly
      process and the performance indicators, including sensitivity, linear range of
      detection, anti-jamming performance, and stability, of the electrochemical
      immunosensor were examined by cyclic voltammetry (CV) and electrochemical
      impedance spectroscopy (EIS). RESULTS: With optimized experimental conditions,
      the difference of the current value measured by differential pulse voltammetry
      (DPV) showed a linear relationship with the concentration of serum trypsin within
      0.10-100 ng/mL. The detection limit for trypsin using this sensor was 0.002
      ng/mL. CONCLUSIONS: The electrochemical immunosensor built using the MWCNT
      composite-modified electrode is simple to operate and has a fast response time,
      along with a wide linear range, high sensitivity, and accuracy, making it
      suitable for serum trypsin detection.

PMID- 24919019
TI  - Clinical significance of p95HER2 overexpression, PTEN loss and PI3K expression in
      p185HER2-positive metastatic breast cancer patients treated with trastuzumab
      based therapies.
AB  - Retraction to: British Journal of Cancer (2014) 110, 1968-1976;
      doi:10.1038/bjc.2014.72. It has been brought to our attention that, as a result
      of a miscommunication, the antibody used in this study in order to determine the
      expression of p95 HER2 in metastatic breast cancer patients is in fact directed
      against p95 NBS1, a component of the MRN complex, and is completely unrelated to
      p95 HER2. Therefore, a relationship between p95 HER2 overexpression and outcome
      cannot be established based on the results described and we wish to retract our
      paper. The authors, the editors of British Journal of Cancer, and the referees of
      this paper are grateful to colleagues in the field who have brought this problem
      to our attention and we apologise for any confusion that has, inadvertently, been
      caused.

PMID- 24919021
TI  - Orhan Bukulmez, MD.

PMID- 24919022
TI  - Common practices in reproductive endocrinology and infertility supported by weak
      or no evidence.

PMID- 24919023
TI  - Food and drug supplements to improve fertility outcomes.
AB  - Food and drug supplements (FDS) are extensively used by infertile couples either
      to supplement medical infertility treatment and assisted conception or as a means
      to independently improve conception rates. The majority of FDS are composed of
      antioxidants that are used for male and female infertility. Their use, despite
      being biologically plausible, lacks scientific support due to limitations
      stemming from poorly designed small studies. FDS and for that matter
      complementary and alternative medicine (CAM) is plagued by fallacies that confuse
      or mislead the public and thus may prevent many patients from making the right
      therapeutic decisions regarding their infertility problem. We do concur that the
      absence of evidence is not the evidence of absence; however, one should be wary
      of the apparent benign effects of FDS and CAM. The current literature seems to
      suggest a beneficial effect of antioxidants on male infertility. There is,
      however, no FDS that has been proven beyond doubt to increase conception rates in
      female infertility. The additive value of CAM and FDS on the success of assisted
      conception is also not known. Well-designed randomized studies are urgently
      needed given the popularity and ever increasing consumption of these supplements
      by the infertile couples. 

PMID- 24919025
TI  - Best protocol for controlled ovarian hyperstimulation in assisted reproductive
      technologies: fact or opinion?
AB  - From the early ages of assisted reproductive technologies (ARTs), different
      protocols have been developed with different gonadotropin preparations at
      different dosages with or without gonadotropin releasing hormone agonist or
      antagonist cotreatment. Various adjuvants have also been incorporated in
      controlled ovarian hyperstimulation (COH) protocols in an attempt to increase the
      efficacy and safety. The "best" protocol for COH should minimize stimulation
      burden while maintain the highest healthy, singleton, term live birth rates.
      Understandably, the one that meets all these expectations may not exist and COH
      should be individualized. Currently, there are worldwide differences in COH
      protocols and gonadotropin dose algorithms used depending on the country,
      demographics, funding stream, and existing guidelines/legislations. In 2014,
      despite efforts to individualize COH, currently, many of the protocols employ
      lack of high-quality evidence-based data. The aim of this review is to overview
      the efficacy and safety of available COH protocols, in normal responders, poor
      responders, and hyperresponders from evidence-based medicine perspective. 

PMID- 24919024
TI  - Surgical treatment before assisted reproductive technologies.
AB  - Advances in technology have transformed surgery from a major approach into an art
      of science capable of treating many diseases and conditions in a less risky way.
      This advance let physicians perform surgery commonly in their practice. Today,
      surgery in reproductive medicine has become so customary that evidence has not
      been questioned commonly. Therefore, this review will help reproductive
      endocrinologists to read the most recent evidence for surgery to improve in vitro
      fertilization outcome. This will also help them to inform their patients with the
      most recent evidence. 

PMID- 24919026
TI  - Laboratory procedures for human in vitro fertilization.
AB  - Successful and consistent outcomes in human in vitro fertilization (IVF) can be
      readily achieved by all IVF clinics through consideration and optimization of
      each procedure associated with the collection and processing of gametes,
      culminating in the resultant culture and transfer of healthy embryos.
      Furthermore, understanding the interactions between the individual components of
      the IVF cycle will assist when trouble-shooting possible problems in a laboratory
      which could have an adverse effect on cycle outcome. This article will review
      handling of oocytes and embryo culture, preparation of gametes for insemination
      and microinjection, selection of the most viable gametes and embryos,
      cryopreservation, and successful embryo transfer from the laboratory perspective.

PMID- 24919027
TI  - Intracytoplasmic sperm injection indications: how rigorous?
AB  - Up to 15% of all couples of reproductive age are diagnosed with subfertility and
      about one-third of those will have male factor infertility as a contributing
      factor. Intracytoplasmic sperm injection (ICSI) has proven to be invaluable for
      couples with severely compromised semen parameters. Since its introduction into
      the clinical practice in 1992, the indications for ICSI were dramatically
      expanded to include various patient populations with normal or mildly abnormal
      semen parameters. Moreover, some fertility programs choose to perform ICSI for
      all of their patients needing assisted reproductive technologies. By all means,
      the male factor indications for ICSI are not well defined, apart from its
      absolute utility with surgically obtained spermatozoa in the presence of low
      motility, or in cases of severe defects with sperm concentration and motility.
      Based on current evidence, ICSI is not indicated for routine use. Its adoption
      for previous history of total fertilization failure, in vitro oocyte maturation,
      cryopreserved oocytes, polyploidy prevention, poor-quality oocytes, diminished
      ovarian reserve, and advanced reproductive age are not supported by current
      evidence, albeit further research with well-designed studies is warranted.
      Finally, from a biological standpoint ICSI is considered to be more invasive,
      more energy consuming for the oocyte itself and its adverse genetic and
      epigenetic effects cannot be ruled out. Although more studies are needed to
      clarify definitive indications for ICSI, many of its current applications can be
      deemed empiric at this time. 

PMID- 24919028
TI  - Practice of embryo transfer: recommendations during and after.
AB  - Many patient and embryo factors influence the outcome of assisted reproductive
      technology (ART) treatment. The predictors for a successful ART cycle include
      female age, ovarian reserve, embryo quality, endometrial receptivity, and embryo
      transfer (ET) technique. ET, the final step of ART, has recently been noted as a
      crucial step affecting ART success. Variables affecting pregnancy rates following
      ET include ultrasound guidance, ease of ET transfer, catheter type, transfer and
      catheter-loading technique, blood or mucus effects, retained embryos, trial
      transfer, the physician's experience, and catheter tip placement. Despite the
      lack of consensus regarding the optimal ET technique, it is generally recommended
      that during ET, the disruption of the endometrium and the induction of uterine
      contractions should be avoided. The exposure of embryos to the ambient conditions
      should be minimized, and the embryo(s) should be placed at an optimal position
      within the fundal region of the uterine cavity. 

PMID- 24919029
TI  - Remedies for recurrent implantation failure.
AB  - In vitro fertilization (IVF) is expensive, time consuming, and the most
      successful treatment of fertility; however, in general the cumulative chance of
      having a live birth with the treatment is still around 40%. Many couples still
      remain unsuccessful after several IVF attempts, causing deep impact on quality of
      life, and each failed cycle causing a financial burden. Several adjuvant
      therapies have been used along with IVF to increase the pregnancy rates for women
      with repeated implantation failure. Testing of adjuvant therapies in properly
      conducted randomized controlled trials is rarely done so that potential benefits
      and risks are unlikely to be clearly presented to patients and clinicians. In
      this review, we assessed the effects of adjuvants, such as growth hormone,
      androgens, and glucocorticoids to enhance oocyte number and quality; sildenafil,
      low-dose aspirin, heparin, corticosteroids, granulocyte colony-stimulating
      factor, endometrial injury, intrauterine injection of human chorionic
      gonadotropin, and intrauterine administration of autologous peripheral blood
      mononuclear cells to improve poor endometrial response; antioxidants,
      complementary and alternative medicine modalities, such as Chinese herbal
      medicine and acupuncture; and assisted hatching and preimplantation genetic
      screening to correct embryonic factors. 

PMID- 24919030
TI  - Indications of intrauterine insemination for male and non-male factor
      infertility.
AB  - Intrauterine insemination (IUI) is a widely used fertility treatment for couples
      with male and/or non-male factor infertility and is a relatively simple and
      inexpensive procedure. When used for unexplained infertility, IUI combined with
      ovarian stimulation increases the pregnancy rates, but evidence does not support
      this to be true when applied for male factor infertility. Recently, the revised
      World Health Organization laboratory manual for semen criteria provided a new
      insight for practical guidelines. Further randomized, controlled studies are
      necessary to develop standardized IUI strategies. The authors reviewed, via
      literature search, on the indications, prognostic factors, ovarian stimulation
      protocols, and methods that have been employed for IUI treatment. 

PMID- 24919031
TI  - Medical management of male infertility in the absence of a specific etiology.
AB  - Idiopathic male infertility can be diagnosis in approximately one-third of
      infertile males. The empirical medical treatment with or without assisted
      reproductive techniques appears common in male infertility practice. This type of
      management can be classified as hormonal treatment including gonadotropins,
      antiestrogens, and aromatase inhibitors and support with antioxidant supplements
      such as carnitine, lycopene, glutathione, and vitamin E. This review investigates
      the evidence of commonly used empirical medical management of male infertility
      when there is no demonstrable diagnosis. 

PMID- 24919032
TI  - Treatment modalities in recurrent miscarriages without diagnosis.
AB  - Recurrent miscarriage is defined as the loss of three consecutive pregnancies
      before 20 weeks' gestational age. Patients are referred to subspecialists such as
      reproductive endocrinology or maternal fetal medicine to exclude the most common
      causes of recurrent miscarriage including autoimmune disorders, structural
      uterine pathology, metabolic derangements, hematologic conditions, and
      chromosomal abnormalities. Unfortunately, this extensive list of conditions
      accounts for less than 50% of patients affected by recurrent miscarriage, leaving
      the remaining 50% without answers. Multiple treatment modalities, including
      supplementation with progesterone, human chorionic gonadotropin, aspirin with and
      without heparin, and immune modulators have been tested for this large percentage
      of patients with very few answers. In fact, the only successful intervention
      addressed in the literature consists of supportive care at a dedicated recurrent
      miscarriage clinic. Without large randomized clinical trials, there is no
      evidence to support the use of supplemental medications in this patient
      population. 

PMID- 24919033
TI  - Metformin and other insulin sensitizers in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex disorder affecting a substantial
      group of women from adolescent to menopausal age groups. A substantial subgroup
      of these women exhibits increased insulin resistance. Insulin resistance is
      difficult to establish in clinical practice and many surrogate tests are
      available, although their value in the clinical setting is uncertain. The QUICKI
      method is an inexpensive and easy test to administer and is probably the best
      test to be used in PCOS patients, preferably in a clinical trial context. There
      is considerable evidence that insulin-sensitizing agents are not contributory to
      infertility management in the majority of women with PCOS. Currently, there is no
      evidence that cardiovascular morbidity is decreased by long-term use of insulin
      sensitizers in PCOS women. 

PMID- 24919034
TI  - Response-Adaptive Allocation for Circular Data.
AB  - Response-adaptive designs are used in phase III clinical trials to allocate a
      larger proportion of patients to the better treatment. Circular data is a natural
      outcome in many clinical trial setup, e.g., some measurements in opthalmologic
      studies, degrees of rotation of hand or waist, etc. There is no available work on
      response-adaptive designs for circular data. With reference to a dataset on
      cataract surgery we provide some response-adaptive designs where the responses
      are of circular nature and propose some test statistics for treatment comparison
      under adaptive data allocation procedure. Detailed simulation study and the
      analysis of the dataset, including redesigning the cataract surgery data, are
      carried out. 

PMID- 24919035
TI  - Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte
      differentiation.
AB  - The ZHTc6-MyoD embryonic stem cell line expresses the myogenic transcriptional
      factor MyoD under the control of a tetracycline-inducible promoter. Following
      induction, most of the ZHTc6-MyoD cells differentiate to myotubes. However, a
      small fraction does not differentiate, instead forming colonies that retain the
      potential for myocyte differentiation. In our current study, we found that
      parathyroid hormone type 1 receptor (PTH1R) expression in colony-forming cells at
      13 days after differentiation was higher than that in the undifferentiated ZHTc6
      MyoD cells. We also found that PTH1R expression was required for myocyte
      differentiation, and that parathyroid hormone accelerated the differentiation.
      Our analysis of human and mouse skeletal muscle tissues showed that most cells
      expressing PTH1R also expressed Pax7 and CD34, which are biomarkers of satellite
      cells. Furthermore, we found that parathyroid hormone treatment significantly
      improved muscle weakness in dystrophin-deficient mdx mice. This is the first
      report indicating that PTH1R and PTH accelerate myocyte differentiation. 

PMID- 24919036
TI  - Laparoscopic partial splenectomy performed by monopolar saline-cooled
      radiofrequency coagulation.
AB  - BACKGROUND: Partial splenectomy is preferred to total splenectomy when possible
      to reduce the risk of life-threatening infection. Several techniques have been
      described, each with its merits. Laparoscopic transection with monopolar saline
      cooled radiofrequency coagulation has not been previously described. PATIENTS AND
      METHODS: Two patients with enlarging cystic splenic lesions consented to
      laparoscopic partial splenectomy. In 1 case, high-power saline-cooled monopolar
      radiofrequency transection was performed with a laparoscopic sealing hook; the
      procedure was performed with a rigid resectoscope and ball diathermy in the
      other. RESULTS: Both cases were performed without complications. Transection with
      the resectoscope and ball diathermy was combined with selective clamping of the
      splenic hilar vessels and was performed in 100 minutes with estimated blood loss
      of 250 mL. Transection with the sealing hook was performed in 80 minutes without
      hilar vessel clamping, with an estimated blood loss of 100 mL. No additional
      hemostatic agents were required for either case. CONCLUSIONS: Laparoscopic
      partial splenectomy can be performed with monopolar saline-cooled radiofrequency
      for parenchymal transection and hemostasis in a simple and effective manner.

PMID- 24919037
TI  - Genotoxic evaluation, secondary metabolites and antioxidant capacity of leaves
      and roots of Urera baccifera Gaudich (Urticaceae).
AB  - In addition to phenolics, flavonoids, flavonols, alkaloids and condensed tannins,
      our tests identified the antioxidant and genotoxic properties in the crude
      extract (CE) and fractions of Urera baccifera (Urticaceae) roots and leaves.
      Oxalic acid (OA) content was determined by HPLC-DAD, which presented high values
      in the roots (1.82 +/- 0.21, 1.79 +/- 0.22 and 1.38 +/- 0.15 mg/g in butanolic,
      CE and ethyl acetate fraction, respectively). OA caused a 30.7% reduction in the
      leucocyte proliferation, followed by butanolic fractions of roots (24.15%) and
      leaves (23.28%). The mitotic index was lower in butanolic fractions of leaves
      (8.7%) and roots (8.3%), similar to the OA index, which was 6.0%. The DNA damage
      index in cultured leukocytes was observed for OA (19.33) and butanol fraction
      treatments (22.67 and 16, respectively, for leaves and roots). Antioxidant
      capacity (DPPH and TBARS) was moderated, which was confirmed by the low phenolic,
      flavonol and flavonoid contents in both parts of the plant.

PMID- 24919038
TI  - Predicting failure: acoustic emission of berlinite under compression.
AB  - Acoustic emission has been measured and statistical characteristics analyzed
      during the stress-induced collapse of porous berlinite, AlPO4, containing up to
      50 vol% porosity. Stress collapse occurs in a series of individual events
      (avalanches), and each avalanche leads to a jerk in sample compression with
      corresponding acoustic emission (AE) signals. The distribution of AE avalanche
      energies can be approximately described by a power law p(E)dE = E(-epsilon)dE
      (epsilon ~ 1.8) over a large stress interval. We observed several collapse
      mechanisms whereby less porous minerals show the superposition of independent
      jerks, which were not related to the major collapse at the failure stress. In
      highly porous berlinite (40% and 50%) an increase of energy emission occurred
      near the failure point. In contrast, the less porous samples did not show such an
      increase in energy emission. Instead, in the near vicinity of the main failure
      point they showed a reduction in the energy exponent to ~ 1.4, which is
      consistent with the value reported for compressed porous systems displaying
      critical behavior. This suggests that a critical avalanche regime with a lack of
      precursor events occurs. In this case, all preceding large events were 'false
      alarms' and unrelated to the main failure event. Our results identify a method to
      use pico-seismicity detection of foreshocks to warn of mine collapse before the
      main failure (the collapse) occurs, which can be applied to highly porous
      materials only.

PMID- 24919039
TI  - Ag-ZnO nanoreactor grown on FTO substrate exhibiting high heterogeneous
      photocatalytic efficiency.
AB  - This Research Article reports an unusually high efficiency heterogeneous
      photodegradation of methyl orange (MO) in the presence of Ag nanoparticle-loaded
      ZnO quasi-nanotube or nanoreactor (A-ZNRs) nanocatalyst grown on FTO substrate.
      In typical process, photodegradation efficiency of as high as 21.6% per MUg per
      Watts of used catalyst and UV power can be normally obtained within only a 60-min
      reaction time from this system, which is 10(3) order higher than the reported
      results. This is equivalent to the turnover frequency of 360 mol mol(-1) h(-1).
      High-density hexagonal A-ZNRs catalysts were grown directly on FTO substrate via
      a seed-mediated microwave-assisted hydrolysis growth process utilizing Ag
      nanoparticle of approximately 3 nm in size as nanoseed and mixture aqueous
      solution of Zn(NO3).6H2O, hexamethylenetetramine (HMT), and AgNO3 as the growth
      solution. A-ZNRs adopts hexagonal cross-section morphology with the inner surface
      of the reactor characterized by a rough and rugged structure. Transmission
      electron microscopy imaging shows the Ag nanoparticle grows interstitially in the
      ZnO nanoreactor structure. The high photocatalytic property of the A-ZNRs is
      associated with the highly active of inner side's surface of A-ZNRs and the
      oxidizing effect of Ag nanoparticle. The growth mechanism as well as the
      mechanism of the enhanced-photocatalytic performance of the A-ZNRs will be
      discussed. 

PMID- 24919040
TI  - Calcification of Cryopreserved Arterial Graft Causing Delayed Obstruction of
      Portal Vein Flow After Liver Transplant.
AB  - In patients with biliary atresia, portal vein problems may cause challenges for
      liver transplant. Interposition grafts have been used for vascular anastomoses in
      transplant recipients with varied success. A cryopreserved iliac artery graft was
      used for the reconstruction of the portal vein in a 29-month-old infant with
      biliary atresia. At 17 months after transplant, she developed upper
      gastrointestinal bleeding that was caused by portal vein occlusion because of
      vascular calcifications in the graft. Upper gastrointestinal endoscopy showed
      esophageal varices with fresh bleeding, and the varices were band ligated. At 3
      months after the bleeding episode, the patient was asymptomatic and biochemical
      tests were normal. In summary, liver transplant with cryopreserved iliac artery
      graft may be complicated by calcifications and portal vein occlusion, and caution
      is advised in using this graft material for portal vein anastomoses. 

PMID- 24919041
TI  - Three-dimensional spatiotemporal features for fast content-based retrieval of
      focal liver lesions.
AB  - Content-based image retrieval systems for 3-D medical datasets still largely rely
      on 2-D image-based features extracted from a few representative slices of the
      image stack. Most 2 -D features that are currently used in the literature not
      only model a 3-D tumor incompletely but are also highly expensive in terms of
      computation time, especially for high-resolution datasets. Radiologist-specified
      semantic labels are sometimes used along with image-based 2-D features to improve
      the retrieval performance. Since radiological labels show large interuser
      variability, are often unstructured, and require user interaction, their use as
      lesion characterizing features is highly subjective, tedious, and slow. In this
      paper, we propose a 3-D image-based spatiotemporal feature extraction framework
      for fast content-based retrieval of focal liver lesions. All the features are
      computer generated and are extracted from four-phase abdominal CT images.
      Retrieval performance and query processing times for the proposed framework is
      evaluated on a database of 44 hepatic lesions comprising of five pathological
      types. Bull's eye percentage score above 85% is achieved for three out of the
      five lesion pathologies and for 98% of query lesions, at least one same type of
      lesion is ranked among the top two retrieved results. Experiments show that the
      proposed system's query processing is more than 20 times faster than other
      already published systems that use 2-D features. With fast computation time and
      high retrieval accuracy, the proposed system has the potential to be used as an
      assistant to radiologists for routine hepatic tumor diagnosis. 

PMID- 24919042
TI  - Morphological changes in the liver and kidneys of rats subjected to terminal
      ileum exclusion during obstructive cholestasis.
AB  - PURPOSE: To investigate the effects of ileal exclusion on hepatic and renal
      morphology in extra-hepatic cholestasis. METHODS: Twenty four rats were
      distributed into three groups. Group 1 (control) underwent laparotomy and
      laparorrhaphy. The animals in groups 2 and 3 underwent hepatic duct ligature and
      kept in cholestasis for four weeks. After this period, the rats in groups 2 and 3
      underwent internal biliary derivation. In Group 3, the last ten centimeters of
      the terminal ileum were by passed and excluded. Four weeks later, histological
      and biochemical analysis were performed in all animals of the three groups.
      RESULTS: In Group 1, no abnormalities regarding hepatic morphology were observed.
      All animals from groups 2 and 3 presented hepatic fibrosis. No difference was
      observed between the two groups. No morphological differences in renal histology
      could be identified among the three groups. There were differences in AST
      (p<0.05), ALT (p<0.05), direct bilirubin (p<0.05), GammaGT (p<0.05), urea
      (p<0.05) and creatinine (p<0.05) in Group 3 compared to control. CONCLUSION: The
      distal ileum exclusion had no influence upon the hepatic and renal morphological
      alterations, and biochemical liver and kidney tests have worsened.

PMID- 24919043
TI  - Mesenteric lymph reperfusion after superior mesenteric artery occlusion shock
      exacerbates endotoxin translocation in brain.
AB  - PURPOSE: To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin
      translocation in brain to discuss the mechanism of brain injury subjected to
      superior mesenteric artery occlusion (SMAO) shock. METHODS: Twenty-four rats were
      randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by
      clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion
      for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery
      (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of
      both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO
      group rats. RESULTS: SMAO shock induced severe increased levels of the endotoxin,
      lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular
      adhesion molecule-1 and tumor necrosis factor-alpha. Concurrently, MLR after SMAO
      shock further aggravates these deleterious effects. CONCLUSION: Mesenteric lymph
      reperfusion exacerbated the endotoxin translocation in brain; thereby increased
      inflammatory response occurred, suggesting that the intestinal lymph pathway
      plays an important role in the brain injury after superior mesenteric artery
      occlusion shock.

PMID- 24919044
TI  - Glutamine and ornithine alpha-ketoglutarate supplementation on malate
      dehydrogenases expression in hepatectomized rats.
AB  - PURPOSE: To evaluate the relative gene expression (RGE) of cytosolic (MDH1) and
      mitochondrial (MDH2) malate dehydrogenases enzymes in partially hepatectomized
      rats after glutamine (GLN) or ornithine alpha-ketoglutarate (OKG) suplementation.
      METHODS: One-hundred and eight male Wistar rats were randomly distributed into
      six groups (n=18): CCaL, GLNL and OKGL and fed calcium caseinate (CCa), GLN and
      OKG, 0.5 g/Kg by gavage, 30 minutes before laparotomy. CCaH, GLNH and OKGH groups
      were likewise fed 30 minutes before 70% partial hepatectomy. Blood and liver
      samples were collected three, seven and 14 days after laparotomy/hepatectomy for
      quantification of MDH1/MDH2 enzymes using the real-time polymerase chain reaction
      (PCR) methodology. Relative enzymes expression was calculated by the 2
      (DeltaDeltaC)T method using the threshold cycle (CT) value for normalization.
      RESULTS: MDH1/MDH2 RGE was not different in hepatectomized rats treated with OKG
      compared to rats treated with CCa. However, MDH1/MDH2 RGE was greater on days 3
      (321:1/26.48:1) and 7 (2.12:1/2.48:1) while MDH2 RGE was greater on day 14
      (7.79:1) in hepatectomized rats treated with GLN compared to control animals.
      CONCLUSION: Glutamine has beneficial effects in liver regeneration in rats by
      promoting an up-regulation of the MDH1 and MDH2 relative gene expression.

PMID- 24919045
TI  - Antiperoxidative properties of oil mixes of high ratio Omega-9:Omega-6 and low
      ratio Omega-6:Omega-3 after molar extraction in rats.
AB  - PURPOSE: To evaluate the antioxidant and antiperoxidative effects of oil mixes of
      high ratio Omega-9:Omega-6 and low ratio Omega-6:Omega-3 in the third day after
      tooth extraction in rats. METHODS: Thirty-two male Wistar rats (270-310 g) were
      randomly distributed in two groups: Control (n=24) and Test (n=8). Control group
      was divided into three subgroups (n=8): G1: Sham-Saline; G2: Saline; G3:
      Isolipid. G1 and G2 animals received NaCl 0.9% while G3 rats were treated with an
      isolipid mixture (alpha-linolenic acid - ALA) containing -6/-3 oils (8:1 ratio)
      and-9/-6 (0.4:1 ratio). Test group animals (G4) received oily mixtures (alpha
      linolenic acid - ALA, docosahexaenoic acid - DHA, eicosapentaenoic acid - EPA) of
      -6/-3 (1.4:1 ratio) and -9/-6 (3.4:1 ratio). Saline and oils were administered by
      gavage during four days before and three days after first mandibular molar
      extraction. Following, samples (arterial blood and alveolar mucosa) were
      collected for glutathione (GSH) and thiobarbituric acid reactive substances
      (TBARS) assays. RESULTS: Oil mixes induced a significant decrease in GSH and
      TBARS tissue and plasma concentrations in the third day post-surgery. CONCLUSION:
      Gavage administration of oil mixes of high ratio Omega-9:Omega-6 and low ratio
      Omega-6:Omega-3 after molar extraction in rats induces a significant decrease in
      lipid peroxidation.

PMID- 24919046
TI  - In-vivo bone response to titanium screw implants anodized in sodium sulfate.
AB  - PURPOSE: To evaluate the early bone response to a nanotextured dental implant
      treated with sodium sulfate (Na2SO4), using a rabbit model. METHODS: Twelve
      animals were randomly divided into group 1 (Control) - machined implants and
      group 2 (Test) - nanotextured implants. Extra-oral incision was performed to
      provide access to intended surgical site where the dental implant was inserted
      immediately after the extraction of the mandibular first premolar. Implant
      surface characterization was performed by scanning electron microscopy attached
      to energy dispersive spectroscopy and interferometry. Three weeks after surgery,
      the animals were induced to death and undecalcified sections of the samples were
      prepared for histological and histomorphometrical analysis. RESULTS: Surface
      characterization of the implant demonstrated enhanced surface area of anodized
      group compared to Control group with 19.2% +/- 6.2 versus 1.6 +/- 0.7,
      respectively. Histological evaluation demonstrated new bone formation starting
      from the buccal and lingual cortical walls on both groups. After three weeks,
      significant higher bone contact of 27% (p<0.05) was observed to nanotextured
      compared to machined implants (Control group). CONCLUSION: The anodization with
      sodium sulfate nanostructures to the implant surface that resulted in faster
      osseointegration.

PMID- 24919047
TI  - A cadaveric study to determine the minimum volume of methylene blue to completely
      color the nerves of brachial plexus in cats. An update in forelimb and shoulder
      surgeries.
AB  - PURPOSE: To determine the minimum volume of methylene blue (MB) to completely
      color the brachial plexus (BP) nerves, simulating an effective anesthetic block
      in cats. METHODS: Fifteen adult male cat cadavers were injected through
      subscapular approach with volumes of 2, 3, 4, 5 and 6 ml in both forelimbs, for a
      total of 30 brachial plexus blocks (BPB). After infusions, the specimens were
      carefully dissected preserving each nervous branch. The measurement of the
      effective area was indicated by the impregnation of MB. Nerves were divided into
      four segments from the origin at the spinal level until the insertion into the
      thoracic limb muscles. The blocks were considered effective only when all the
      nerves were strongly or totally colored. RESULTS: Volumes of 2, 3 and 4 ml were
      considered insufficient suggesting a failed block, however, volumes of 5 and 6 ml
      were associated with a successful block. CONCLUSIONS: The injection of methylene
      blue, in a volume of 6 ml, completely colored the brachial plexus. At volumes of
      5 and 6 ml the brachial plexus blocks were considered a successful regional
      block, however, volumes of 2, 3 and 4 ml were considered a failed regional block.

PMID- 24919048
TI  - Epidemiological features of esophageal cancer. Squamous cell carcinoma versus
      adenocarcinoma.
AB  - PURPOSE: To analyze the epidemiological features of patients with esophageal
      cancer according to the histopathological types: squamous cell carcinoma or
      adenocarcinoma. METHODS: A total of 100 patients with esophageal cancer, being 50
      squamous cell carcinomas and 50 adenocarcinomas were analyzed for demographics,
      nutritional factors, lifestyle habits, benign pathological conditions associated,
      like Barrett's esophagus and megaesophagus, tumor stage and survival rates. The
      nutritional factors evaluated included body mass index, percent weight loss,
      hemoglobin and albumin serum levels. RESULTS: Esophageal cancer occurred more
      often in men over 50 years-old in both histological groups. No significant
      differences on age and gender were found between the histological groups.
      Squamous cell carcinoma was significantly more frequent in blacks than
      adenocarcinoma. Alcohol consumption and smoking were significantly associated
      with squamous cell carcinoma. Higher values of body mass index were seen in
      patients with adenocarcinoma. Barrett's esophagus was found in nine patients
      (18%) with adenocarcinoma, and megaesophagus in two patients (4%) with squamous
      cell carcinoma. The majority of patients were on stages III and IV in both
      histological groups. The mean survival rates were 7.7 +/- 9.5 months for patients
      with squamous cell carcinoma and 8.0 +/- 10.9 months for patients with
      adenocarcinoma. No significant differences on tumor stage and survival rates were
      detected between the histological groups. CONCLUSION: Epidemiological features
      are distinct for the histopathological types of esophageal cancer. Squamous cell
      carcinoma is associated with black race, alcohol and smoking, while
      adenocarcinoma is related to higher body mass index, white race and Barrett's
      esophagus.

PMID- 24919049
TI  - Cardiorespiratory evaluation in pre and post operative moments of laparoscopic
      cholecystectomy.
AB  - PURPOSE: To analyze the changes in both respiratory function and cardiopulmonary
      exercise tests results in patients subjected to laparoscopic cholecystectomy.
      METHODS: Fifty patients were evaluated (76% women) and the average age was 47.8
      +/- 14.2 years. All individuals underwent the measurement of spirometry,
      manovacuometry, 6-minute walk test (6MWT) and stair-climbing test (SCT). All
      tests were performed at the first (PO1), fifth (PO5) and thirtieth (PO30)
      postoperative days. RESULTS: BMI average was 28.8 +/- 4.8 kg/m(2). Sample
      comprised 68% non-smokers, 20% current smokers, and 12% former smokers. There was
      no incidence of postoperative complication whatsoever. There was a significant
      decrease in spirometric values at PO1, but values were similar to the ones of PRE
      at PO30. Manovacuometry showed alterations at PO1 displaying values that were
      similar to the ones of PRE at PO30. 6MWT was significantly shorter at until PO5,
      but at PO30 values were similar to ones of PRE. As for SCT, values were
      significantly compromised at PO5 and PO30 since they were similar to the ones of
      PRE. CONCLUSION: Patients submitted to laparoscopic cholecystectomy present a
      decrease in cardiorespiratory function on the first postoperative moments but
      there is a rapid return to preoperative conditions.

PMID- 24919050
TI  - Influence of clinical therapy and nutritional counseling on the recurrence of
      urolithiasis.
AB  - PURPOSE: To evaluate the influence of combined clinical therapy and nutritional
      guidance on the recurrence of urolithiasis. METHODS: From our registry of
      patients with recurrent urolithiasis we selected 57 who had at least 5-years of
      follow-up. We collected 24h urine samples in order to analyze Ca, Na, uric acid,
      citrate, oxalate, and Mg concentrations and to assess urine volume. Patients
      filled out a clinical questionnaire before treatment, and abdominal radiographs
      and/or ultrasound were performed both before treatment and during the follow-up
      period. During follow-up, specific and individualized dietary advice was given
      based on the individual's metabolic disorders. Patients also received specific
      pharmacological treatment for their metabolic alterations. Outcome measures were
      metabolites in urine and the urolith recurrence rate. Pre- and post- intervention
      values were compared using tests as appropriate. RESULTS: Fifty six of the
      patients were male and the majority of patients were overweight. The mean BMI was
      27 kg/m(2). Urinary excretion of calcium, uric acid and sodium decreased
      significantly over the five year follow-up period. The number of uroliths that
      formed during the 5-year follow-up also decreased significantly compared to pre
      treatment values. CONCLUSION: Individualized dietary advice combined with
      pharmacological treatment significantly reduces long-term urolithiasis
      recurrence.

PMID- 24919051
TI  - Microsurgical training model with nonliving swine head. Alternative for
      neurosurgical education.
AB  - PURPOSE: This paper proposes a practical model of microneurosurgical training
      using a nonliving swine head. METHODS: Fresh porcine heads were obtained from
      butchery and dissected at our Laboratory of Microsurgery. Brain and skull base
      surgery were trained under microscopic magnification. RESULTS: Several
      neurosurgical procedures could be simulated in the nonliving pig model, including
      transcallosal approach to the lateral ventricle, lateral sulcus and middle fossa
      dissection, and posterior fossa surgery. CONCLUSION: The swine model perfectly
      simulates standard microneurosurgical procedures, and is a useful tool for
      developing and refining surgical skills.

PMID- 24919053
TI  - Anthropogenic disturbance and biodiversity of marine benthic communities in
      Antarctica: a regional comparison.
AB  - The impacts of two Antarctic stations in different regions, on marine sediment
      macrofaunal communities were compared: McMurdo, a very large station in the Ross
      Sea; and Casey, a more typical small station in East Antarctica. Community
      structure and diversity were compared along a gradient of anthropogenic
      disturbance from heavily contaminated to uncontaminated locations. We examined
      some of the inherent problems in comparing data from unrelated studies, such as
      different sampling methods, spatial and temporal scales of sampling and taxonomic
      uncertainty. These issues generated specific biases which were taken into account
      when interpreting patterns. Control sites in the two regions had very different
      communities but both were dominated by crustaceans. Community responses to
      anthropogenic disturbance (sediment contamination by metals, oils and sewage)
      were also different. At McMurdo the proportion of crustaceans decreased in
      disturbed areas and polychaetes became dominant, whereas at Casey, crustaceans
      increased in response to disturbance, largely through an increase in amphipods.
      Despite differing overall community responses there were some common elements.
      Ostracods, cumaceans and echinoderms were sensitive to disturbance in both
      regions. Capitellid, dorvelleid and orbiniid polychaetes were indicative of
      disturbed sites. Amphipods, isopods and tanaids had different responses at each
      station. Biodiversity and taxonomic distinctness were significantly lower at
      disturbed locations in both regions. The size of the impact, however, was not
      related to the level of contamination, with a larger reduction in biodiversity at
      Casey, the smaller, less polluted station. The impacts of small stations, with
      low to moderate levels of contamination, can thus be as great as those of large
      or heavily contaminated stations. Regional broad scale environmental influences
      may be important in determining the composition of communities and thus their
      response to disturbance, but there are some generalizations regarding responses
      which will aid future management of stations. 

PMID- 24919052
TI  - Comparative effectiveness of long term drug treatment strategies to prevent
      asthma exacerbations: network meta-analysis.
AB  - OBJECTIVE: To determine the comparative effectiveness and safety of current
      maintenance strategies in preventing exacerbations of asthma. DESIGN: Systematic
      review and network meta-analysis using Bayesian statistics. DATA SOURCES:
      Cochrane systematic reviews on chronic asthma, complemented by an updated search
      when appropriate. ELIGIBILITY CRITERIA TRIALS OF Adults with asthma randomised to
      maintenance treatments of at least 24 weeks duration and that reported on asthma
      exacerbations in full text. Low dose inhaled corticosteroid treatment was the
      comparator strategy. The primary effectiveness outcome was the rate of severe
      exacerbations. The secondary outcome was the composite of moderate or severe
      exacerbations. The rate of withdrawal was analysed as a safety outcome. RESULTS:
      64 trials with 59,622 patient years of follow-up comparing 15 strategies and
      placebo were included. For prevention of severe exacerbations, combined inhaled
      corticosteroids and long acting beta agonists as maintenance and reliever
      treatment and combined inhaled corticosteroids and long acting beta agonists in a
      fixed daily dose performed equally well and were ranked first for effectiveness.
      The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95%
      credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other
      combined strategies were not superior to inhaled corticosteroids and all single
      drug treatments were inferior to single low dose inhaled corticosteroids. Safety
      was best for conventional best (guideline based) practice and combined
      maintenance and reliever therapy. CONCLUSIONS: Strategies with combined inhaled
      corticosteroids and long acting beta agonists are most effective and safe in
      preventing severe exacerbations of asthma, although some heterogeneity was
      observed in this network meta-analysis of full text reports.

PMID- 24919055
TI  - Relationship between apparent diffusion coefficient and tumour cellularity in
      lung cancer.
AB  - BACKGROUND AND OBJECTIVE: To prospectively investigate the relationship between
      the apparent diffusion coefficient (ADC) and cellularity in lung cancer. METHODS:
      Sixty patients histopathologically confirmed with lung cancer (41 men, 19 women)
      underwent diffusion-weighted magnetic resonance imaging of the chest (with b
      values of 50 and 1000 s/mm2). The median mean ADC (ADC mean) value and median
      minimum ADC (ADC min) value within each primary tumour were calculated and
      compared with the median nucleo-cytoplasmic ratio (NCR), which was selected to
      represent the cellularity. The correlation between the NCR and ADC mean/ADC min
      was calculated with SPSS 18.0 software. RESULTS: The mean ADC mean values, ADC
      min values and median NCR were (1.07 +/- 0.12) * 10(-3) mm2/s, (0.86 +/- 0.14) *
      10(-3) mm2/s, and (14.9 +/- 2.6) %, respectively, in adenocarcinoma; (0.88 +/-
      0.10) * 10(-3) mm2/s, (0.73 +/- 0.12) * 10(-3)) mm2/s, and (20.6 +/- 4.4) %,
      respectively, in squamous cell carcinoma; and (0.89 +/- 0.13) * 10(-3) mm2/s,
      (0.67 +/- 0.13) * 10(-3) mm2/s, and (18.3 +/- 3.5) %, respectively in small cell
      lung cancer. The NCR of squamous cell carcinoma and small cell lung cancer is
      greater than that of adenocarcinoma (P < 0.01 and P = 0.002, respectively). There
      was an inverse relationship between ADC mean/NCR and ADC min/NCR (r = -0.60, P =
      0.001 and r = -0.47, P < 0.001, respectively). CONCLUSION: There is a significant
      inverse relationship between tumour cellularity and ADC in lung cancer. However,
      tumour cellularity most likely is not the sole determinant of the ADC.

PMID- 24919054
TI  - Individual differences in ethanol locomotor sensitization are associated with
      dopamine D1 receptor intra-cellular signaling of DARPP-32 in the nucleus
      accumbens.
AB  - In mice there are clear individual differences in the development of behavioral
      sensitization to ethanol, a progressive potentiation of its psychomotor stimulant
      effect. Variability in the behavioral responses to ethanol has been associated
      with alcohol preference. Here we investigated if the functional
      hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to
      an increased activation of DARPP-32, a central regulatory protein in medium spiny
      neurons, in the nucleus accumbens - a brain region known to play a role in drug
      reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p.
      administrations for 21 days and were weekly evaluated regarding their locomotor
      activity. From those treated with ethanol, the 33% with the highest levels of
      locomotor activity were classified as "sensitized" and the 33% with the lowest
      levels as "non-sensitized". The latter presented similar locomotor levels to
      those of saline-treated mice. Different subgroups of mice received intra
      accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor
      agonist 0.1 or 1 ug/side. Indeed, sensitized mice presented functional
      hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the
      ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20
      min before the euthanasia. The nucleus accumbens were dissected for the Western
      Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1
      receptor activation induced higher phospho-Thr34-DARPP-32 expression in
      sensitized mice than in non-sensitized or saline. The functionally
      hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with
      an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation.
      These data suggest that an enduring increase in the sensitivity of the dopamine
      D1 receptor intracellular pathway sensitivity represents a neurobiological
      correlate associated with the development of locomotor sensitization to ethanol. 

PMID- 24919056
TI  - Atropisomerism about aryl-Csp(3) bonds: the electronic and steric influence of
      ortho-substituents on conformational exchange in cannabidiol and linderatin
      derivatives.
AB  - Terpenylation reactions of substituted phenols were used to prepare cannabidiol
      and linderatin derivatives, and their structure and conformational behavior in
      solution were investigated by NMR and, for some representative examples, by DFT.
      VT-NMR spectra and DFT calculations were used to determine the activation
      energies of the conformational change arising from restricted rotation about the
      aryl-Csp(3) bond that lead to two unequally populated rotameric epimers. The NBO
      calculation was applied to explain the electronic stabilization of one conformer
      over another by donor-acceptor charge transfer interactions. Conformational
      control arises from a combination of stereoelectronic and steric effects between
      substituents in close contact with each other on the two rings of the endocyclic
      epoxide atropisomers. This study represents the first exploration of the
      stereoelectronic origins of atropisomerism around C(sp(2))-C(sp(3)) single bonds
      through theoretical calculations. 

PMID- 24919057
TI  - Effects of crowding on the stability of a surface-tethered biopolymer: an
      experimental study of folding in a highly crowded regime.
AB  - The high packing densities and fixed geometries with which biomolecules can be
      attached to macroscopic surfaces suggest that crowding effects may be
      particularly significant under these often densely packed conditions. Exploring
      this question experimentally, we report here the effects of crowding on the
      stability of a simple, surface-attached DNA stem-loop. We find that crowding by
      densely packed, folded biomolecules destabilizes our test-bed biomolecule by ~2
      kJ/mol relative to the dilute (noninteracting) regime, an effect that presumably
      occurs due to steric and electrostatic repulsion arising from compact neighbors.
      Crowding by a dense brush of unfolded biomolecules, in contrast, enhances its
      stability by ~6 kJ/mol, presumably due to excluded volume and electrostatic
      effects that reduce the entropy of the unfolded state. Finally, crowding by like
      copies of the same biomolecule produces a significantly broader unfolding
      transition, likely because, under these circumstances, the stabilizing effects of
      crowding by unfolded molecules increase (and the destabilizing effects of
      neighboring folded molecules decrease) as more and more neighbors unfold. The
      crowding of surface-attached biomolecules may thus be a richer, more complex
      phenomenon than that seen in homogeneous solution.

PMID- 24919058
TI  - Bioremediation of a complex industrial effluent by biosorbents derived from
      freshwater macroalgae.
AB  - Biosorption with macroalgae is a promising technology for the bioremediation of
      industrial effluents. However, the vast majority of research has been conducted
      on simple mock effluents with little data available on the performance of
      biosorbents in complex effluents. Here we evaluate the efficacy of dried biomass,
      biochar, and Fe-treated biomass and biochar to remediate 21 elements from a real
      world industrial effluent from a coal-fired power station. The biosorbents were
      produced from the freshwater macroalga Oedogonium sp. (Chlorophyta) that is
      native to the industrial site from which the effluent was sourced, and which has
      been intensively cultivated to provide a feed stock for biosorbents. The effect
      of pH and exposure time on sorption was also assessed. These biosorbents showed
      specificity for different suites of elements, primarily differentiated by ionic
      charge. Overall, biochar and Fe-biochar were more successful biosorbents than
      their biomass counterparts. Fe-biochar adsorbed metalloids (As, Mo, and Se) at
      rates independent of effluent pH, while untreated biochar removed metals (Al, Cd,
      Ni and Zn) at rates dependent on pH. This study demonstrates that the biomass of
      Oedogonium is an effective substrate for the production of biosorbents to
      remediate both metals and metalloids from a complex industrial effluent. 

PMID- 24919059
TI  - Prolonged low intensity EPOCH-rituximab has improved toxicity in Burkitt lymphoma
      compared with standard short, high intensity therapy.
AB  - Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma that has a short
      doubling time, thus intense short-cycle chemotherapy has been thought to be
      essential. A recent NCI-sponsored clinical trial investigated DA-EPOCH-R given to
      19 HIV-negative patients and a short course regimen (SC-EPOCH-RR) given to 11 HIV
      positive patients in hopes of maintaining the efficacy of the regimen while
      decreasing the typical side effects from the intensive short-cycle chemotherapy.
      Low intensity EPOCH-R based therapy achieved excellent rates of efficacy despite
      a significant difference in the median cumulative dose between the DA-EPOCH-R and
      SC-EPOCH-RR cohorts. Furthermore, both cohorts experienced mainly grade 1 and
      grade 2 toxicities, with SC-EPOCH-RR cohort patients experiencing less adverse
      events than DA-EPOCH-R cohort patients. This recent clinical investigation
      suggests the most important therapeutic principle is not the intensity but rather
      the length of exposure time above an effective threshold concentration. Since
      short, intense bolus doses are the standard therapy for Burkitt lymphoma, these
      findings are clinically relevant and significant. 

PMID- 24919060
TI  - Charge state-dependent catalytic activity of [Au(25)(SC(12)H(25))18] nanoclusters
      for the two-electron reduction of dioxygen to hydrogen peroxide.
AB  - The electrochemical production of H2O2 from O2 catalyzed by [Au25(SC12H25)18] was
      studied as a function of the charge state (-1, 0 and +1). Maximum H2O2 production
      (~90%) was obtained from the negatively charged clusters (Au25(-)) due to the
      efficient electron transfer from the anionic Au25(-) cluster into the LUMO (pi*)
      of O2. 

PMID- 24919061
TI  - Long-term MRI cell tracking after intraventricular delivery in a patient with
      global cerebral ischemia and prospects for magnetic navigation of stem cells
      within the CSF.
AB  - BACKGROUND: The purpose of the study was to evaluate the long-term clinical
      tracking of magnetically labeled stem cells after intracerebroventricular
      transplantation as well as to investigate in vitro feasibility for magnetic
      guidance of cell therapy within large fluid compartments. METHOD: After approval
      by our Institutional Review Board, an 18-month-old patient, diagnosed as being in
      a vegetative state due to global cerebral ischemia, underwent cell
      transplantation to the frontal horn of the lateral ventricle, with umbilical cord
      blood-derived stem cells labeled with superparamagnetic iron oxide (SPIO)
      contrast agent. The patient was followed over 33 months with clinical
      examinations and MRI. To evaluate the forces governing the distribution of cells
      within the fluid compartment of the ventricular system in vivo, a gravity-driven
      sedimentation assay and a magnetic field-driven cell attraction assay were
      developed in vitro. RESULTS: Twenty-four hours post-transplantation, MR imaging
      (MRI) was able to detect hypointense cells in the occipital horn of the lateral
      ventricle. The signal gradually decreased over 4 months and became undetectable
      at 33 months. In vitro, no significant difference in cell sedimentation between
      SPIO-labeled and unlabeled cells was observed (p = NS). An external magnet was
      effective in attracting cells over distances comparable to the size of human
      lateral ventricles. CONCLUSIONS: MR imaging of SPIO-labeled cells allows
      monitoring of cells within lateral ventricles. While the initial biodistribution
      is governed by gravity-driven sedimentation, an external magnetic field may
      possibly be applied to further direct the distribution of labeled cells within
      large fluid compartments such as the ventricular system.

PMID- 24919062
TI  - Improving the accuracy and efficiency of respiratory rate measurements in
      children using mobile devices.
AB  - The recommended method for measuring respiratory rate (RR) is counting breaths
      for 60 s using a timer. This method is not efficient in a busy clinical setting.
      There is an urgent need for a robust, low-cost method that can help front-line
      health care workers to measure RR quickly and accurately. Our aim was to develop
      a more efficient RR assessment method. RR was estimated by measuring the median
      time interval between breaths obtained from tapping on the touch screen of a
      mobile device. The estimation was continuously validated by measuring consistency
      (% deviation from the median) of each interval. Data from 30 subjects estimating
      RR from 10 standard videos with a mobile phone application were collected. A
      sensitivity analysis and an optimization experiment were performed to verify that
      a RR could be obtained in less than 60 s; that the accuracy improves when more
      taps are included into the calculation; and that accuracy improves when
      inconsistent taps are excluded. The sensitivity analysis showed that excluding
      inconsistent tapping and increasing the number of tap intervals improved the RR
      estimation. Efficiency (time to complete measurement) was significantly improved
      compared to traditional methods that require counting for 60 s. There was a trade
      off between accuracy and efficiency. The most balanced optimization result
      provided a mean efficiency of 9.9 s and a normalized root mean square error of
      5.6%, corresponding to 2.2 breaths/min at a respiratory rate of 40 breaths/min.
      The obtained 6-fold increase in mean efficiency combined with a clinically
      acceptable error makes this approach a viable solution for further clinical
      testing. The sensitivity analysis illustrating the trade-off between accuracy and
      efficiency will be a useful tool to define a target product profile for any novel
      RR estimation device.

PMID- 24919063
TI  - Changes in the distribution of red foxes (Vulpes vulpes) in urban areas in Great
      Britain: findings and limitations of a media-driven nationwide survey.
AB  - Urbanization is one of the major forms of habitat alteration occurring at the
      present time. Although this is typically deleterious to biodiversity, some
      species flourish within these human-modified landscapes, potentially leading to
      negative and/or positive interactions between people and wildlife. Hence, up-to
      date assessment of urban wildlife populations is important for developing
      appropriate management strategies. Surveying urban wildlife is limited by land
      partition and private ownership, rendering many common survey techniques
      difficult. Garnering public involvement is one solution, but this method is
      constrained by the inherent biases of non-standardised survey effort associated
      with voluntary participation. We used a television-led media approach to solicit
      national participation in an online sightings survey to investigate changes in
      the distribution of urban foxes in Great Britain and to explore relationships
      between urban features and fox occurrence and sightings density. Our results show
      that media-based approaches can generate a large national database on the current
      distribution of a recognisable species. Fox distribution in England and Wales has
      changed markedly within the last 25 years, with sightings submitted from 91% of
      urban areas previously predicted to support few or no foxes. Data were highly
      skewed with 90% of urban areas having <30 fox sightings per 1000 people km(-2).
      The extent of total urban area was the only variable with a significant impact on
      both fox occurrence and sightings density in urban areas; longitude and
      percentage of public green urban space were respectively, significantly
      positively and negatively associated with sightings density only. Latitude, and
      distance to nearest neighbouring conurbation had no impact on either occurrence
      or sightings density. Given the limitations associated with this method, further
      investigations are needed to determine the association between sightings density
      and actual fox density, and variability of fox density within and between urban
      areas in Britain.

PMID- 24919064
TI  - Assessing knowledge and attitudes of diabetes in Zuni Indians using a culture
      centered approach.
AB  - INTRODUCTION: The Zuni Pueblo, in collaboration with the University of New
      Mexico, have formed the Zuni Health Initiative (ZHI) engaged in community-based
      participatory research to plan and implement educational interventions to reduce
      health disparities. We conducted the first phase of ZHI study and identified
      barriers to healthcare. We concluded that the burden presented by these barriers
      ultimately translates into a lack of patient activation and engagement in their
      health care including for diabetes, effectively hindering adoption of healthy
      behaviors. METHODS: Community health representatives (CHRs) led 10 one-hour focus
      group sessions to elicit information on diabetes knowledge and self-management
      strategies at which a total of 84 people participated. Audiotapes were translated
      and transcribed by bilingual ZHI staff. We reduced the text to thematic
      categories, constructed a coding dictionary and inserted the text into NVivo 9
      program. RESULTS: The focus groups revealed that despite extensive personal or
      family experiences with diabetes or complications, participants identified
      knowledge gaps in the disease progression and disease management. However, we
      gained insight into how many Zunis conceptualize the etiology of diabetes, risk
      factors associated with diabetes, sources of knowledge and self-management
      practices. CONCLUSION: We concluded that many of the Zuni diabetics experience
      significant impacts on their life when they were diagnosed with diabetes and
      suffered the plight of stigmatization. We further concluded that developing Zuni
      culture specific diabetes care should focus on family involvement with continued
      education.

PMID- 24919065
TI  - Experimental and numerical investigation of the effect of different shapes of
      collars on the reduction of scour around a single bridge pier.
AB  - The scour phenomenon around bridge piers causes great quantities of damages
      annually all over the world. Collars are considered as one of the substantial
      methods for reducing the depth and volume of scour around bridge piers. In this
      study, the experimental and numerical methods are used to investigate two
      different shapes of collars, i.e, rectangular and circular, in terms of reducing
      scour around a single bridge pier. The experiments were conducted in hydraulic
      laboratory at university of Malaya. The scour around the bridge pier and collars
      was simulated numerically using a three-dimensional, CFD model namely SSIIM 2.0,
      to verify the application of the model. The results indicated that although, both
      types of collars provides a considerable decrease in the depth of the scour, the
      rectangular collar, decreases scour depth around the pier by 79 percent, and has
      better performance compared to the circular collar. Furthermore, it was observed
      that using collars under the stream's bed, resulted in the most reduction in the
      scour depth around the pier. The results also show the SSIIM 2.0 model could
      simulate the scour phenomenon around a single bridge pier and collars with
      sufficient accuracy. Using the experimental and numerical results, two new
      equations were developed to predict the scour depth around a bridge pier exposed
      to circular and rectangular collars. 

PMID- 24919066
TI  - Meiotic recombination analyses of individual chromosomes in male domestic pigs
      (Sus scrofa domestica).
AB  - For the first time in the domestic pig, meiotic recombination along the 18
      porcine autosomes was directly studied by immunolocalization of MLH1 protein. In
      total, 7,848 synaptonemal complexes from 436 spermatocytes were analyzed, and
      13,969 recombination sites were mapped. Individual chromosomes for 113 of the 436
      cells (representing 2,034 synaptonemal complexes) were identified by
      immunostaining and fluorescence in situ hybridization (FISH). The average total
      length of autosomal synaptonemal complexes per cell was 190.3 um, with 32.0
      recombination sites (crossovers), on average, per cell. The number of crossovers
      and the lengths of the autosomal synaptonemal complexes showed significant intra-
      (i.e. between cells) and inter-individual variations. The distributions of
      recombination sites within each chromosomal category were similar: crossovers in
      metacentric and submetacentric chromosomes were concentrated in the telomeric
      regions of the p- and q-arms, whereas two hotspots were located near the
      centromere and in the telomeric region of acrocentrics. Lack of MLH1 foci was
      mainly observed in the smaller chromosomes, particularly chromosome 18 (SSC18)
      and the sex chromosomes. All autosomes displayed positive interference, with a
      large variability between the chromosomes. 

PMID- 24919067
TI  - Pharmacological investigations of N-substituent variation in morphine and
      oxymorphone: opioid receptor binding, signaling and antinociceptive activity.
AB  - Morphine and structurally related derivatives are highly effective analgesics,
      and the mainstay in the medical management of moderate to severe pain.
      Pharmacological actions of opioid analgesics are primarily mediated through
      agonism at the u opioid peptide (MOP) receptor, a G protein-coupled receptor.
      Position 17 in morphine has been one of the most manipulated sites on the
      scaffold and intensive research has focused on replacements of the 17-methyl
      group with other substituents. Structural variations at the N-17 of the morphinan
      skeleton led to a diversity of molecules appraised as valuable and potential
      therapeutics and important research probes. Discovery of therapeutically useful
      morphine-like drugs has also targeted the C-6 hydroxyl group, with oxymorphone as
      one of the clinically relevant opioid analgesics, where a carbonyl instead of a
      hydroxyl group is present at position 6. Herein, we describe the effect of N
      substituent variation in morphine and oxymorphone on in vitro and in vivo
      biological properties and the emerging structure-activity relationships. We show
      that the presence of a N-phenethyl group in position 17 is highly favorable in
      terms of improved affinity and selectivity at the MOP receptor, potent agonism
      and antinociceptive efficacy. The N-phenethyl derivatives of morphine and
      oxymorphone were very potent in stimulating G protein coupling and intracellular
      calcium release through the MOP receptor. In vivo, they were highly effective
      against acute thermal nociception in mice with marked increased antinociceptive
      potency compared to the lead molecules. It was also demonstrated that a carbonyl
      group at position 6 is preferable to a hydroxyl function in these N-phenethyl
      derivatives, enhancing MOP receptor affinity and agonist potency in vitro and in
      vivo. These results expand the understanding of the impact of different moieties
      at the morphinan nitrogen on ligand-receptor interaction, molecular mode of
      action and signaling, and may be instrumental to the development of new opioid
      therapeutics. 

PMID- 24919068
TI  - Can quality of life assessments differentiate heterogeneous cancer patients?
AB  - PURPOSE: This research conducted a face validation study of patient responses to
      the application of an HRQOL assessment research tool in a comprehensive community
      cancer program setting across a heterogeneous cohort of cancer patients
      throughout the natural history of diagnosed malignant disease, many of whom would
      not be considered candidates for clinical research trial participation. METHODS:
      Cancer registries at two regional cancer treatment centers identified 11072
      cancer patients over a period of nine years. The EORTC QLQ-C30 was administered
      to patients at the time of their initial clinical presentation to these centers.
      To determine the significance of differences between patient subgroups, two
      analytic criteria were used. The Mann-Whitney test was used to determine
      statistical significance; clinical relevance defined a range of point differences
      that could be perceived by patients with different health states. RESULTS:
      Univariate analyses were conducted across stratification variables for
      population, disease severity and demographic characteristics. The largest
      differences were associated with cancer diagnosis and recurrence of disease.
      Large differences were also found for site of origin, mortality and stage;
      minimal differences were observed for gender and age. Consistently sensitive QoL
      scales were appetite loss, fatigue and pain symptoms, and role (work-related),
      social and physical functions. CONCLUSIONS: 1) The EORTC QLQ-C30 collected
      meaningful patient health assessments in the context of non-research based
      clinical care, 2) patient assessment differences are manifested disparately
      across 15 QoL domains, and 3) in addition to indicating how a patient may feel at
      a point in time, QoL indicators may also reveal information about underlying
      biological responses to disease progression, treatments, and prospective
      survival.

PMID- 24919070
TI  - Dose finding with the sequential parallel comparison design.
AB  - The sequential parallel comparison design (SPCD) is a two-stage design
      recommended for trials with possibly high placebo response. A drug-placebo
      comparison in the first stage is followed in the second stage by placebo
      nonresponders being re-randomized between drug and placebo. We describe how SPCD
      can be used in trials where multiple doses of a drug or multiple treatments are
      compared with placebo and present two adaptive approaches. We detail how to
      analyze data in such trials and give recommendations about the allocation
      proportion to placebo in the two stages of SPCD. 

PMID- 24919069
TI  - Conventional housing conditions attenuate the development of experimental
      autoimmune encephalomyelitis.
AB  - BACKGROUND: The etiology of multiple sclerosis (MS) has remained unclear, but a
      causative contribution of factors outside the central nervous system (CNS) is
      conceivable. It was recently suggested that gut bacteria trigger the activation
      of CNS-reactive T cells and the development of demyelinative disease. METHODS:
      C57BL/6 (B6) mice were kept either under specific pathogen free or conventional
      housing conditions, immunized with the myelin basic protein (MBP)-proteolipid
      protein (PLP) fusion protein MP4 and the development of EAE was clinically
      monitored. The germinal center size of the Peyer's patches was determined by
      immunohistochemistry in addition to the level of total IgG secretion which was
      assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell
      and B cell responses in the Peyer's patches and the spleen. Ear swelling assays
      were performed to determine the extent of delayed-type hypersensitivity reactions
      in specific pathogen free and conventionally housed mice. RESULTS: In B6 mice
      that were actively immunized with MP4 and kept under conventional housing
      conditions clinical disease was significantly attenuated compared to specific
      pathogen free mice. Conventionally housed mice displayed increased levels of IgG
      secretion in the Peyer's patches, while the germinal center formation in the gut
      and the MP4-specific TH17 response in the spleen were diminished after
      immunization. Accordingly, these mice displayed an attenuated delayed type
      hypersensitivity (DTH) reaction in ear swelling assays. CONCLUSIONS: The data
      corroborate the notion that housing conditions play a substantial role in the
      induction of murine EAE and suggest that the presence of gut bacteria might be
      associated with a decreased immune response to antigens of lower affinity. This
      concept could be of importance for MS and calls for caution when considering the
      therapeutic approach to treat patients with antibiotics.

PMID- 24919071
TI  - Leveraging position bias to improve peer recommendation.
AB  - With the advent of social media and peer production, the amount of new online
      content has grown dramatically. To identify interesting items in the vast stream
      of new content, providers must rely on peer recommendation to aggregate opinions
      of their many users. Due to human cognitive biases, the presentation order
      strongly affects how people allocate attention to the available content.
      Moreover, we can manipulate attention through the presentation order of items to
      change the way peer recommendation works. We experimentally evaluate this effect
      using Amazon Mechanical Turk. We find that different policies for ordering
      content can steer user attention so as to improve the outcomes of peer
      recommendation. 

PMID- 24919072
TI  - Characterization of the xiamenmycin biosynthesis gene cluster in Streptomyces
      xiamenensis 318.
AB  - Xiamenmycin (1) is a prenylated benzopyran derivative with anti-fibrotic
      activity. To investigate the genetic basis of xiamenmycin biosynthesis, we
      performed genome mining in the xiamenmycin-producing Streptomyces xiamenensis
      wild-type strain 318 to identify a candidate gene cluster. The complete gene
      cluster, consisting of five genes, was confirmed by a series of gene
      inactivations and heterologous expression. Based on bioinformatics analyses of
      each gene and feeding experiments, we found that the structure of an intermediate
      xiamenmycin B (3) accumulated in a ximA inactivation mutant, allowing us to
      propose a biosynthetic pathway. All five of the genes in the pathway were
      genetically and biochemically characterized. XimA was biochemically characterized
      as an ATP-dependent amide synthetase, catalyzing an amide bond formation in the
      presence of ATP as the final step in Xiamenmycin biosynthesis. The Km value of
      XimA was determined to be 474.38 uM for the substrate xiamenmycin B. These
      studies provide opportunities to use genetic and chemo-enzymatic methods to
      create new benzopyran derivatives as potential therapeutic agents. 

PMID- 24919073
TI  - Mobility, continence, and life expectancy in persons with Asia Impairment Scale
      Grade D spinal cord injuries.
AB  - OBJECTIVE: Previous research on the life expectancy of persons with American
      Spinal Injury Association (ASIA) Impairment Scale Grade D spinal cord injury has
      considered them as a large homogenous group, making no functional or medical
      distinctions. This study sought to (1) determine how survival in this group
      depends on ambulatory function and the extent of bowel or bladder dysfunction,
      (2) compute life expectancies for various subgroups, and (3) examine whether
      survival has improved over time. DESIGN: Data were from 8,206 adults with ASIA
      Impairment Scale Grade D spinal cord injury in the Spinal Cord Injury Model
      Systems database who were not ventilator dependent and who survived more than 1
      yr after injury. There were a total of 114,739 person-years of follow-up and
      1,730 deaths during the 1970-2011 study period. Empirical age- and sex-specific
      mortality rates were computed. Regression analysis of survival data with time
      dependent covariates was used to determine the effect of risk factors, to test
      for a time trend, and to estimate mortality rates for subgroups. Life
      expectancies were obtained from life tables constructed for each subgroup.
      RESULTS: The ability to walk, whether independently or with an assistive device,
      was associated with longer survival than wheelchair dependence. The need for an
      indwelling catheter, and to a lesser extent intermittent catheterization, was
      associated with increased mortality risk. Persons who walked unaided and who did
      not require catheterization had life expectancies roughly 90% of normal. Those
      who required a wheelchair for locomotion had life expectancies comparable with
      that in paraplegia, less than 75% of normal. No time trend in survival was found.
      CONCLUSIONS: Life expectancy of persons with ASIA Impairment Scale D spinal cord
      injury depends strongly on the ability to walk and the need for catheterization.

PMID- 24919074
TI  - RE: Effectiveness of extracorporeal shock wave therapy in chronic plantar
      fasciitis.

PMID- 24919075
TI  - Energy cost of obstacle crossing in stroke patients.
AB  - OBJECTIVE: The purpose of this study was to analyze the effects of clearing and
      skirting obstacles during the gait on the energetic cost of walking (ECW) of
      patients with chronic hemiplegia. The hypothesis was that hemiplegia would have a
      greatest increase in the ECW than in the healthy group. DESIGN: Fifteen healthy
      subjects and 17 patients with chronic hemiplegia completed two 6-min walking
      sessions: one with obstacles and the other without obstacles. During both
      sessions, the patients were equipped with a portable gas analyzer to measure
      oxygen uptake (Vo2). Gait velocity and ECW were calculated. RESULTS: In both
      groups, gait velocity was lower in the with-obstacles condition and the ECW was
      significantly higher. Vo2 was greater in the with-obstacles condition for the
      healthy group, whereas it remained unchanged for the group with hemiplegia.
      CONCLUSIONS: Results demonstrated that the addition of obstacles during gait
      increased the ECW and decreased mean walking speed in both the healthy subjects
      and the patients with hemiplegia. More interestingly, the authors found
      differences in adaptation strategies between the healthy subjects and the
      patients with hemiplegia. During the with-obstacles condition, the oxygen uptakes
      of the healthy subjects increased and mean walking speed decreased, whereas, in
      the subjects with hemiplegia, only mean walking speed decreased.

PMID- 24919076
TI  - Recovery of injured oculomotor nerve in a patient with intracerebral hemorrhage.

PMID- 24919077
TI  - Transcranial direct current stimulation to primary motor area improves hand
      dexterity and selective attention in chronic stroke.
AB  - OBJECTIVE: The aim of this study was to determine whether transcranial direct
      current stimulation (tDCS) applied to the primary motor hand area modulates hand
      dexterity and selective attention after stroke. DESIGN: This study was a double
      blind, placebo-controlled, randomized crossover trial involving subjects with
      chronic stroke. Ten stroke survivors with some pinch strength in the paretic hand
      received three different tDCS interventions assigned in random order in separate
      sessions-anodal tDCS targeting the primary motor area of the lesioned hemisphere
      (M1lesioned), cathodal tDCS applied to the contralateral hemisphere
      (M1nonlesioned), and sham tDCS-each for 20 mins. The primary outcome measures
      were Purdue pegboard test scores for hand dexterity and response time in the
      color-word Stroop test for selective attention. Pinch strength of the paretic
      hand was the secondary outcome. RESULTS: Cathodal tDCS to M1nonlesioned
      significantly improved affected hand dexterity (by 1.1 points on the Purdue
      pegboard unimanual test, P = 0.014) and selective attention (0.6 secs faster
      response time on the level 3 Stroop interference test for response inhibition, P
      = 0.017), but not pinch strength. The outcomes were not improved with anodal tDCS
      to M1lesioned or sham tDCS. CONCLUSIONS: Twenty minutes of cathodal tDCS to
      M1nonlesioned can promote both paretic hand dexterity and selective attention in
      people with chronic stroke.

PMID- 24919078
TI  - Can American Board of Physical Medicine and Rehabilitation Part 2 board
      examination scores be predicted from rotation evaluations or mock oral
      examinations?
AB  - OBJECTIVE: The aim of this study was to determine whether either Physical
      Medicine and Rehabilitation residency performance on core competency evaluations
      or on practice mock oral examinations is correlated to performance on future
      American Board of Physical Medicine and Rehabilitation Part 2 board-certifying
      examination. DESIGN: This is a retrospective cohort study of residents who took
      part 2 of the American Board of Physical Medicine and Rehabilitation
      certification examination between 1995 and 2011 (N = 31 or 38 or 67). RESULTS:
      The postgraduate year 4 mock oral examination average achieved significance in
      correlation analysis (Spearman rho, 0.0391; P = 0.030). Patient care and a
      composite average of the other core competencies evaluations were also
      significantly correlated with performance on part 2 of the board-certifying
      examination (Spearman rho, 0.329; P = 0.044). The only independent variable that
      was uniquely predictive was postgraduate year 4 mock oral examinations (chi =
      7.09; P = 0.029). More specifically, when controlling for rotation performances,
      residents with higher mock oral examination scores were 9.6 times (Exp B = 9.6;
      95% confidence interval, 1.2-80; P = 0.036) more likely than those one grade
      lower to achieve the upper half on oral board examinations vs. either of the
      lower 2 quartiles. CONCLUSIONS: The postgraduate year 4 mock oral examinations
      and the core competency evaluations composite are each predictive of performance
      on American Board of Physical Medicine and Rehabilitation part 2 examination.
      Further research into this area, with a larger sample size and with multiple
      institutions, would be helpful to allow for a better measurement of these
      evaluation tools' effectiveness.

PMID- 24919079
TI  - Interface stress in socket/residual limb with transtibial prosthetic suspension
      systems during locomotion on slopes and stairs.
AB  - OBJECTIVE: This study aimed to compare the effects of different suspension
      methods on the interface stress inside the prosthetic sockets of transtibial
      amputees when negotiating ramps and stairs. DESIGN: Three transtibial prostheses,
      with a pin/lock system, a Seal-In system, and a magnetic suspension system, were
      created for the participants in a prospective study. Interface stress was
      measured as the peak pressure by using the F-socket transducers during stairs and
      ramp negotiation. RESULTS: Twelve individuals with transtibial amputation managed
      to complete the experiments. During the stair ascent and descent, the greatest
      peak pressure was observed in the prosthesis with the Seal-In system. The
      magnetic prosthetic suspension system caused significantly different peak
      pressure at the anterior proximal region compared with the pin/lock (P = 0.022)
      and Seal-In (P = 0.001) during the stair ascent. It was also observed during the
      stair descent and ramp negotiation. CONCLUSIONS: The prostheses exhibited varying
      pressure profiles during the stair and ramp ascent. The prostheses with the
      pin/lock and magnetic suspension systems exhibited lower peak pressures compared
      with the Seal-In system. The intrasystem pressure distribution at the anterior
      and posterior regions of the residual limb was fairly homogenous during the stair
      and ramp ascent and descent. Nevertheless, the intrasystem pressure mapping
      revealed a significant difference among the suspension types, particularly at the
      anterior and posterior sensor sites.

PMID- 24919080
TI  - Ankle muscular proprioceptive signals' relevance for balance control on various
      support surfaces: an exploratory study.
AB  - OBJECTIVE: The purpose of this study was to test the effect of various unstable
      support surfaces on the relevance of muscular proprioceptive signals originating
      from the ankle joint. DESIGN: Ten healthy subjects were instructed to stand as
      still as possible on a force plate during 40 secs on three different surfaces:
      (1) stable, (2) unstable-unspecific (foam), and (3) unstable-specific (inspired
      from rearfoot anatomy). Muscular vibration was applied on the paraspinals and
      fibularis muscles. The effects of vibrations on postural stability as well as
      fibularis longus and tibialis anterior electrical activities for each support
      condition were investigated. RESULTS: The unstable-specific support surface was
      associated with higher fibularis muscular activity and greater postural
      perturbations when fibularis muscles were vibrated than the unspecific-unstable
      surface. CONCLUSION: Balance control on unstable-specific support surface
      maintains the relevance on muscular proprioceptive signals originating from ankle
      and increases ankle evertor muscle activity.

PMID- 24919081
TI  - Ganglion cyst at the fibular head causing common peroneal neuropathy diagnosed
      with ultrasound and electrodiagnostic examination: a case report.
AB  - The common peroneal nerve is a major source of innervation to the lower limb, but
      it is sometimes compressed or entrapped at the fibular head. The authors present
      what they believe is the first reported case where peroneal nerve impingement
      caused by ganglion cyst compression of the nerve at the fibular head was
      diagnosed using a combination of ultrasound imaging and electrodiagnostic
      studies. The authors described the history, physical examination,
      electrodiagnostic findings, and musculoskeletal ultrasound findings of a patient
      with a left foot drop caused by a ganglion cyst compressing the common peroneal
      nerve at the fibular head. The increasing role of ultrasound imaging to evaluate
      musculoskeletal pathology is discussed. 

PMID- 24919082
TI  - A descriptive comparison of sprint cycling performance and neuromuscular
      characteristics in able-bodied athletes and paralympic athletes with cerebral
      palsy.
AB  - OBJECTIVE: This study investigated the sprint cycling performance and
      neuromuscular characteristics of Paralympic athletes with cerebral palsy (CP)
      during a fatiguing maximal cycling trial compared with those of able-bodied (AB)
      athletes. DESIGN: Five elite athletes with CP and 16 AB age- and performance
      matched controls performed a 30-sec Wingate cycle test. Power output (W/kg) and
      fatigue index (%) were calculated. Electromyography was measured in five
      bilateral muscles and expressed in mean amplitude (mV) and median frequency (Hz).
      RESULTS: Power output was significantly higher in the AB group (10.4 [0.5] W/kg)
      than in the CP group (9.8 [0.5] W/kg) (P < 0.05). Fatigue index was statistically
      similar between the AB (27% [0.1%]) and CP (25% [0.1%]) groups. Electromyographic
      mean amplitude and frequency changed similarly in all muscle groups tested, in
      both affected and nonaffected sides, in the CP and AB groups (P < 0.05).
      Neuromuscular irregularities were identified in the CP group. CONCLUSIONS: The
      similarity in fatigue between the CP and AB groups indicates that elite athletes
      with CP may have a different exercise response to others with CP. The authors
      propose that this may result from high-level training over many years. This has
      rehabilitative implications, as it indicates near-maximal adaptation of the CP
      body toward normal levels.

PMID- 24919083
TI  - Urogenital pruritus in association with lumbar spinal stenosis.

PMID- 24919084
TI  - Ischiofemoral impingement revisited: what physiatrists need to know in short.

PMID- 24919085
TI  - Ultrasound imaging of the accessory nerve injury in a patient with thrombotic
      thrombocytopenic purpura and polyneuropathy.

PMID- 24919086
TI  - Ultrastable PbSe nanocrystal quantum dots via in situ formation of atomically
      thin halide adlayers on PbSe(100).
AB  - The fast degradation of lead selenide (PbSe) nanocrystal quantum dots (NQDs) in
      ambient conditions impedes widespread deployment of the highly excitonic, thus
      versatile, colloidal NQDs. Here we report a simple in situ post-synthetic halide
      salt treatment that results in size-independent air stability of PbSe NQDs
      without significantly altering their optoelectronic characteristics. From TEM,
      NMR, and XPS results and DFT calculations, we propose that the unprecedented size
      independent air stability of the PbSe NQDs can be attributed to the successful
      passivation of under-coordinated PbSe(100) facets with atomically thin PbX2 (X =
      Cl, Br, I) adlayers. Conductive films made of halide-treated ultrastable PbSe
      NQDs exhibit markedly improved air stability and behave as an n-type channel in a
      field-effect transistor. Our simple in situ wet-chemical passivation scheme will
      enable broader utilization of PbSe NQDs in ambient conditions in many
      optoelectronic applications. 

PMID- 24919087
TI  - The prevalence and risk factors for depression symptoms in a rural Chinese sample
      population.
AB  - BACKGROUND: It is essential to understand how we can prevent and treat the
      epidemic of depression. Several studies have reported the prevalence of
      depressive symptoms in the urban population in China, but there is a lack of
      information regarding the prevalence of depression in rural populations.
      OBJECTIVE: To understand the prevalence of depression in a rural Chinese
      population and to analyze the risk factors for depression. METHODS: This study
      used a cross-sectional approach. A total of 11,473 subjects were surveyed and
      completed the Patient Health Questionnaire-9 (PHQ-9) and the World Health
      Organization Quality of Life Brief scales. Living conditions, per capita income,
      marital status, and information about dietary health and chronic disease status
      were assessed. RESULTS: The prevalence of depressive symptoms in the population
      was 5.9%. The prevalence in women (8.1%) was higher compared with men (3.5%) and
      also increased with age. The per capita income level, amount of sleep obtained
      per day, education level, weekly consumption of meat and beans or bean products,
      salt intake, and chronic disease status were associated with depressive symptoms.
      The quality of life of individuals with a score less than 10 points on the PHQ-9
      was significantly better compared with individuals with a score greater than 10.
      CONCLUSION: The prevalence of depressive symptoms among rural population is
      higher than some southern cities in China. Dietary patterns may be an important
      risk factor linked to this disorder in the Chinese rural population.

PMID- 24919088
TI  - Hospital based emergency department visits attributed to child physical abuse in
      United States: predictors of in-hospital mortality.
AB  - OBJECTIVES: To describe nationally representative outcomes of physical abuse
      injuries in children necessitating Emergency Department (ED) visits in United
      States. The impact of various injuries on mortality is examined. We hypothesize
      that physical abuse resulting in intracranial injuries are associated with worse
      outcome. MATERIALS AND METHODS: We performed a retrospective analysis of the
      Nationwide Emergency Department Sample (NEDS), the largest all payer hospital
      based ED database, for the years 2008-2010. All ED visits and subsequent
      hospitalizations with a diagnosis of "Child physical abuse" (Battered baby or
      child syndrome) due to various injuries were identified using ICD-9-CM
      (International Classification of Diseases, 9th Revision, Clinical Modification)
      codes. In addition, we also examined the prevalence of sexual abuse in this
      cohort. A multivariable logistic regression model was used to examine the
      association between mortality and types of injuries after adjusting for a
      multitude of patient and hospital level factors. RESULTS: Of the 16897 ED visits
      that were attributed to child physical abuse, 5182 (30.7%) required
      hospitalization. Hospitalized children were younger than those released treated
      and released from the ED (1.9 years vs. 6.4 years). Male or female partner of the
      child's parent/guardian accounted for >45% of perpetrators. Common injuries in
      hospitalized children include- any fractures (63.5%), intracranial injuries
      (32.3%) and crushing/internal injuries (9.1%). Death occurred in 246 patients (13
      in ED and 233 following hospitalization). Amongst the 16897 ED visits, 1.3% also
      had sexual abuse. Multivariable analyses revealed each 1 year increase in age was
      associated with a lower odds of mortality (OR = 0.88, 95% CI = 0.81-0.96, p <
      0.0001). Females (OR = 2.39, 1.07-5.34, p = 0.03), those with intracranial
      injuries (OR = 65.24, 27.57-154.41, p<0.0001), or crushing/internal injury (OR =
      4.98, 2.24-11.07, p<0.0001) had higher odds of mortality compared to their male
      counterparts. CONCLUSIONS: In this large cohort of physically abused children,
      younger age, females and intracranial or crushing/internal injuries were
      independent predictors of mortality. Identification of high risk cohorts in the
      ED may enable strengthening of existing screening programs and optimization of
      outcomes.

PMID- 24919089
TI  - Macuahuitloides inexpectans n. gen., n. sp. (Molineidae: Anoplostrongylinae) from
      Mormoops megalophylla (Chiroptera: Mormoopidae).
AB  - Macuahuitloides inexpectans n. gen., n. sp. (Molineidae: Anoplostrongylinae) is
      herein described. The description is based on specimens removed from the small
      intestine of ghost-faced bats, Mormoops megalophylla, from central Mexico. The
      monotypic genus is unique in featuring sexual dimorphism on the cuticular
      ornamentation, which consists of the presence of spines on the anterior quarter
      of females, and of the presence of rugosities on the surface of the cephalic
      vesicle of males. The cuticular spines are arranged in spiral rings on the
      anterior quarter of the body, and there is no trace of said structures on the
      cuticle of males. The synlophe of the males possess 12 ridges, whereas there is
      no synlophe in females. Finally, females show a prominent caudal terminus (spine)
      and 3 subterminal tubercles, whereas males show bursal rays in a 3-2 arrangement,
      with a relatively prominent dorsal ray. 

PMID- 24919090
TI  - What's your hunch about improving health care?

PMID- 24919091
TI  - Innovating Mickey Mouse.

PMID- 24919092
TI  - Spiritual uncertainty: exemplars of 2 hospice patients.
AB  - Spirituality is important to persons approaching the end of life. The ambiguous
      nature of dying and spirituality creates many opportunities for uncertainty. This
      article presents 2 exemplars from hospice patients about the different ways that
      spiritual uncertainty affected their dying experience. 

PMID- 24919093
TI  - Paired practica as a pedagogical process in holistic nursing curriculum
      development.
AB  - Nurses have long advocated for significant transformations in the way that care
      is offered. Among advanced holistic nursing programs, there are no particular
      models for developing curricula and practica. This article describes a
      pedagogical process of a holistic health assessment as a context for paired
      practica of graduate and undergraduate nursing students to simultaneously engage
      in knowledge discovery. 

PMID- 24919094
TI  - The effect of royal jelly on oral mucositis in patients undergoing radiotherapy
      and chemotherapy.
AB  - This study was conducted to evaluate the effect of royal jelly on oral mucositis
      in patients undergoing radiotherapy and chemotherapy. The study population
      consisted of 103 patients undergoing radiotherapy and chemotherapy. Oral
      mucositis was graded according to the World Health Organization criteria, and
      patients were divided into 2 groups. All patients received mouthwash therapy with
      benzydamine hydrochloride and nystatin rinses. In addition, patients in the
      experimental group received royal jelly. The mean resolution time of oral
      mucositis in the royal jelly group was significantly shorter than that of the
      control group. As a result, the study results demonstrate that royal jelly
      administrated by a certain procedure improved the signs and symptoms of oral
      mucositis and markedly shortened its healing time. 

PMID- 24919095
TI  - The effect of Sit 'n' Fit Chair Yoga among community-dwelling older adults with
      osteoarthritis.
AB  - The study measured effects of Sit 'N' Fit Chair Yoga on pain and physical and
      psychological functioning. A quasi-experimental research design included a yoga
      intervention group and an attention control group. There was greater improvement
      in depression and life satisfaction in the yoga group than in the control group. 

PMID- 24919096
TI  - Quality of life in women with breast cancer and the use of complementary and
      alternative medicine.
AB  - The aim of this study was to evaluate quality of life and complementary and
      alternative medicine use among patients with breast cancer in Turkey. The sample
      consists of women who had modified undergone radical mastectomy or breast
      conserving surgery. Data were collected using a questionnaire addressing
      personal/medical characteristics use of complementary and alternative medicine
      and the 36-Item Short Form Health Survey (SF-36) to measure quality of life. A
      majority of subjects underwent modified radical mastectomy procedures. The social
      and physical mean scores were the highest and role physical and role emotional
      mean score were the lowest. The most common complementary and alternative methods
      were praying, exercise, and herbs use. In conclusion, women with breast cancer
      have a moderate level of quality of life, and that they use complementary and
      alternative methods widely. 

PMID- 24919097
TI  - The effect of relaxation exercises on quality of sleep among the elderly:
      holistic nursing practice review copy.
AB  - The aim of this study was to determine the effect of relaxation exercises on
      quality of sleep of the elderly people staying in a nursing home. Control group
      had 44 elderly persons and the intervention group had 20 elderly persons in a
      nursing home. Quality of sleep in the intervention group increased statistically
      (P = .000). The elderly people should be encouraged to perform relaxation
      exercises. 

PMID- 24919098
TI  - Psychophytomedicine: an overview of clinical efficacy and phytopharmacology for
      treatment of depression, anxiety and insomnia.

PMID- 24919099
TI  - Microdosimetric analysis confirms similar biological effectiveness of external
      exposure to gamma-rays and internal exposure to 137Cs, 134Cs, and 131I.
AB  - The risk of internal exposure to 137Cs, 134Cs, and 131I is of great public
      concern after the accident at the Fukushima-Daiichi nuclear power plant. The
      relative biological effectiveness (RBE, defined herein as effectiveness of
      internal exposure relative to the external exposure to gamma-rays) is
      occasionally believed to be much greater than unity due to insufficient
      discussions on the difference of their microdosimetric profiles. We therefore
      performed a Monte Carlo particle transport simulation in ideally aligned cell
      systems to calculate the probability densities of absorbed doses in subcellular
      and intranuclear scales for internal exposures to electrons emitted from 137Cs,
      134Cs, and 131I, as well as the external exposure to 662 keV photons. The RBE due
      to the inhomogeneous radioactive isotope (RI) distribution in subcellular
      structures and the high ionization density around the particle trajectories was
      then derived from the calculated microdosimetric probability density. The RBE for
      the bystander effect was also estimated from the probability density, considering
      its non-linear dose response. The RBE due to the high ionization density and that
      for the bystander effect were very close to 1, because the microdosimetric
      probability densities were nearly identical between the internal exposures and
      the external exposure from the 662 keV photons. On the other hand, the RBE due to
      the RI inhomogeneity largely depended on the intranuclear RI concentration and
      cell size, but their maximum possible RBE was only 1.04 even under conservative
      assumptions. Thus, it can be concluded from the microdosimetric viewpoint that
      the risk from internal exposures to 137Cs, 134Cs, and 131I should be nearly
      equivalent to that of external exposure to gamma-rays at the same absorbed dose
      level, as suggested in the current recommendations of the International
      Commission on Radiological Protection. 

PMID- 24919100
TI  - Safety and efficacy of intrastromal injection of 5% natamycin in experimental
      fusarium keratitis.
AB  - PURPOSE: To compare the efficacy of combined intrastromal injection and topical
      natamycin 5% to standard topical therapy alone in an experimental rabbit model of
      Fusarium keratitis. METHODS: Fungal keratitis was induced in the right eyes of 12
      New Zealand rabbits by stromal injection of Fusarium solani spore suspension into
      the cornea. Four days after inoculation, animals were randomly assigned to 2
      different treatment groups (n=6 in each group). The study group received
      intrastromal injections of natamycin 5% on treatment day 1 and 4, combined with
      topical natamycin 5% eye drops given hourly between 8:00 and 20:00 for the first
      2 days, followed by 4 times daily on days 3-11. The control group received only
      topical natamycin 5% at identical intervals. Eyes were examined clinically on
      days 1, 4, 7, and 11 for status of corneal healing, corneal vascularization, and
      hypopyon. Animals were sacrificed on day 11, and corneas were subjected to
      histopathological examination. RESULTS: Both groups showed significant
      improvement in terms of conjunctival hyperemia, size and density of corneal
      infiltrate, corneal edema, and total clinical score. In the study group, there
      was a significant improvement in the height of hypopyon in the anterior chamber,
      while there was also an increased amount of vascularization. CONCLUSIONS: This
      study showed that intrastromal injection of natamycin 5% combined with topical
      treatment has little beneficial effect over topical therapy in a Fusarium
      keratitis rabbit model. The addition of intrastromal injection should be reserved
      to the most severe or recalcitrant cases.

PMID- 24919101
TI  - From the editor.

PMID- 24919102
TI  - Balance training in elderly women using public parks.
AB  - This study evaluates the effects of a balance training program developed in
      public parks on functionality and general state of health in elderly women. It
      was a randomized controlled trial. Women older than 65 years (n = 28; 68.5 +/-
      2.9) participated in a balance training program that lasted 6 weeks, with
      sessions taking place twice a week (12 exercises/session, 50 min). Balance was
      analyzed by the Berg Balance Scale and Timed Up & Go Test. The generic health
      status was measured by the SF-12 Health Survey. These tests showed statistically
      significant differences in the experimental group (p < .05). Public parks are
      adequate installations for developing balance. 

PMID- 24919103
TI  - The relationships between activity and quality of life for older men and women at
      different ages in Taiwan.
AB  - This study investigated the relationships between types of activity and quality
      of life (QOL) for older men and women at different ages. Based on cross-sectional
      data that included 220 community-dwelling elderly persons aged 65 and older in
      southern Taiwan, the results showed that the participation rates in many
      activities declined with age for both genders. Social activity and solitary
      leisure activity were significantly associated with QOL for old-old men, but not
      for young-old men. Only social activity was significantly associated with QOL for
      young-old women, but there was no significant association between any activity
      and QOL for old-old women. 

PMID- 24919104
TI  - Religion in the lives of older women serving life in prison.
AB  - This exploratory qualitative study examined the roles of religiousness in the
      lives of 21 older women (mean age = 63) serving life sentences in one southern
      state. Based on survey and focus group methodology, several themes emerged as
      important focal points, including early religious experiences prior to
      incarceration, imprisonment and religious doubt, participation in formal and
      informal religious activities, and use of religion in coping with stressors such
      as interpersonal relationships, trauma, and health statuses. Irrespective of
      their religious upbringing, all participants agreed that religiosity/spirituality
      played a key role in their ability to cope with their prison experience as well
      as for maintaining hope and the opportunity for release. 

PMID- 24919105
TI  - Seeking and processing information for health decisions among elderly Chinese
      Singaporean women.
AB  - Information behavior includes activities of active information seeking, passive
      acquisition of information, and information use. Guided by the Elaboration
      Likelihood Model, this study explored elderly Singaporean women's health
      information behavior to understand how they sought, evaluated, and used health
      information in everyday lives. Twenty-two in-depth interviews were conducted with
      elderly Chinese women aged 61 to 79. Qualitative analysis of the interview data
      yielded three meta-themes: information-seeking patterns, trustworthiness of
      health information, and peripheral route of decision making. Results revealed
      that elderly women took both systematic and heuristic approaches to processing
      information but relied on interpersonal networks to negotiate health choices. 

PMID- 24919106
TI  - State of inertia: psychological preparation of single Australian and UK baby
      boomer women for retirement housing change.
AB  - The transition into retirement is an important life phase that presents
      significant challenges in respect to well-being, lifestyle, and consumption
      choices. This article examines the consumption context of housing after
      retirement, in particular for the low-resourced cohort of single baby boomer
      women. Utilizing an extended Theory of Planned Behavior model, we examine the
      relationship between intention and actual behavior, in this case financial advice
      seeking, as an important component of the psychological preparedness of single
      female baby boomer women. Our analysis showed both Australian and UK single baby
      boomer women display different behaviors in terms of seeking advice and their
      mental preparedness to adjust to a change in their living arrangements. The
      findings are discussed in terms of their implications for policy and further
      research. 

PMID- 24919109
TI  - Use of amyloid PET across the spectrum of Alzheimer's disease: clinical utility
      and associated ethical issues.
AB  - Abstract Recent advances have made possible the in vivo detection of beta-amyloid
      (Abeta) pathology using positron emission tomography. While the gold standard for
      amyloid imaging, carbon-11 labeled Pittsburgh compound B is increasingly being
      replaced by fluorine-18 labeled radiopharmaceuticals, with three already approved
      for clinical use by US and European regulatory bodies. Appropriate use criteria
      proposed by an amyloid imaging taskforce convened by the Alzheimer's Association
      and the Society of Nuclear Medicine and Molecular Imaging recommend restricting
      use of this technology to the evaluation of patients with mild cognitive
      impairment or atypical dementia syndromes. While use among asymptomatic
      individuals is currently viewed as inappropriate due prognostic uncertainty,
      elevated levels of brain Abeta among asymptomatic individuals may represent
      preclinical Alzheimer's disease. Amyloid imaging is likewise expected to play a
      role in the design of clinical trials. Though preliminary results suggest amyloid
      imaging to possess clinical utility and cost-effectiveness, both domains have yet
      to be assessed systematically. As the field moves toward adoption of a pro
      disclosure stance for amyloid imaging findings, it is imperative that a broad
      range of stakeholders be involved to ensure the appropriateness of emerging
      policies and protocols. 

PMID- 24919110
TI  - A survey of innovation through duplication in the reduced genomes of twelve
      parasites.
AB  - We characterize the prevalence, distribution, divergence, and putative functions
      of detectable two-copy paralogs and segmental duplications in the Apicomplexa, a
      phylum of parasitic protists. Apicomplexans are mostly obligate intracellular
      parasites responsible for human and animal diseases (e.g. malaria and
      toxoplasmosis). Gene loss is a major force in the phylum. Genomes are small and
      protein-encoding gene repertoires are reduced. Despite this genomic streamlining,
      duplications and gene family amplifications are present. The potential for
      innovation introduced by duplications is of particular interest. We compared
      genomes of twelve apicomplexans across four lineages and used orthology and
      genome cartography to map distributions of duplications against genome
      architectures. Segmental duplications appear limited to five species. Where
      present, they correspond to regions enriched for multi-copy and species-specific
      genes, pointing toward roles in adaptation and innovation. We found a phylum-wide
      association of duplications with dynamic chromosome regions and syntenic
      breakpoints. Trends in the distribution of duplicated genes indicate that recent,
      species-specific duplicates are often tandem while most others have been
      dispersed by genome rearrangements. These trends show a relationship between
      genome architecture and gene duplication. Functional analysis reveals: proteases,
      which are vital to a parasitic lifecycle, to be prominent in putative recent
      duplications; a pair of paralogous genes in Toxoplasma gondii previously shown to
      produce the rate-limiting step in dopamine synthesis in mammalian cells, a
      possible link to the modification of host behavior; and phylum-wide differences
      in expression and subcellular localization, indicative of modes of divergence. We
      have uncovered trends in multiple modes of duplicate divergence including
      sequence, intron content, expression, subcellular localization, and functions of
      putative recent duplicates that highlight the role of duplications in the
      continuum of forces that have shaped these genomes. 

PMID- 24919111
TI  - Oxygenation response to positive end-expiratory pressure predicts mortality in
      acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress
      trials.
AB  - RATIONALE: Previous trials of higher positive end-expiratory pressure (PEEP) for
      acute respiratory distress syndrome (ARDS) failed to demonstrate mortality
      benefit, possibly because of differences in lung recruitability among patients
      with ARDS. OBJECTIVES: To determine whether the physiological response to
      increased PEEP is associated with mortality. METHODS: In a secondary analysis of
      the Lung Open Ventilation Study (LOVS, n = 983), we examined the relationship
      between the initial response to changes in PEEP after randomization and
      mortality. We sought to corroborate our findings using data from a different
      trial of higher PEEP (ExPress, n = 749). MEASUREMENTS AND MAIN RESULTS: The
      oxygenation response (change in ratio of arterial partial pressure of oxygen to
      fraction of inspired oxygen: P/F) after the initial change in PEEP after
      randomization varied widely (median, 9.5 mm Hg; interquartile range, -16 to 47)
      and was only weakly related to baseline P/F or the magnitude of PEEP change.
      Among patients in whom PEEP was increased after randomization, an increase in P/F
      was associated with reduced mortality (multivariable logistic regression;
      adjusted odds ratio, 0.80 [95% confidence interval, 0.72-0.89] per 25-mm Hg
      increase in P/F), particularly in patients with severe disease (baseline P/F
      [less-than-or-equal-to] 150 mm Hg). Changes in compliance and dead space were not
      associated with mortality. These findings were confirmed by a similar analysis of
      data from the ExPress trial. CONCLUSIONS: Patients with ARDS who respond to
      increased PEEP by improved oxygenation have a lower risk of death. The
      oxygenation response to PEEP might be used to predict whether patients will
      benefit from higher versus lower PEEP.

PMID- 24919112
TI  - A comparison of nifedipine and tamsulosin as medical expulsive therapy for the
      management of lower ureteral stones without ESWL.
AB  - Administration of nifedipine or tamsulosin has been suggested to augment stone
      expulsion rates. We aimed to compare the stone expulsion rates and adverse
      effects associated with the use of nifedipine or tamsulosin as medical expulsive
      therapy (MET) for the management of lower ureteral stones (LUS) without
      extracorporeal shock wave lithotripsy (ESWL) via a literature review and meta
      analysis. Relevant randomized controlled trials (RCTs) were identified from the
      Medline, EMBASE, Cochrane CENTRAL, and Google Scholar databases. Finally, a total
      of 7 RCTs with 3897 patients were included. Our meta-analysis showed that
      tamsulosin could significantly increase the stone expulsion rate relative to
      nifedipine in patients with LUS (random-effects model; risk ratio [RR] = 0.81;
      95% confidence interval [CI] = 0.75-0.88; P < 0.00001). The subgroup analysis
      indicated no statistically significant difference between the drugs with regard
      to minor or major adverse effects (fixed-effect model; RR = 1.19, 95% CI = 0.91
      1.54, P = 0.20; and RR = 1.63, 95% CI = 0.22-11.82, P = 0.63, respectively). This
      meta-analysis demonstrated that tamsulosin was more effective than nifedipine in
      patients with LUS, as evidenced by the higher stone expulsion rate. Tamsulosin
      treatment should therefore be considered for patients with LUS. 

PMID- 24919113
TI  - Dissolved organic matter quality and bioavailability changes across an
      urbanization gradient in headwater streams.
AB  - Landscape urbanization broadly alters watersheds and stream ecosystems, yet the
      impact of nonpoint source urban inputs on the quantity, quality, and ultimate
      fate of dissolved organic matter (DOM) is poorly understood. We assessed DOM
      quality and microbial bioavailability in eight first-order Coastal Plain
      headwater streams along a gradient of urbanization (i.e., percent watershed
      impervious cover); none of the streams had point source discharges. DOM quality
      was measured using fluorescence excitation-emission matrices (EEMs) coupled with
      parallel factor analysis (PARAFAC). Bioavailability was assessed using
      biodegradable dissolved organic carbon (BDOC) incubations. Results showed that
      watershed impervious cover was significantly related to stream DOM composition:
      increasing impervious cover was associated with decreased amounts of natural
      humic-like DOM and enriched amounts of anthropogenic fulvic acid-like and protein
      like DOM. Microbial bioavailability of DOM was greater in urbanized streams
      during spring and summer, and was related to decreasing proportions of humic-like
      DOM and increasing proportions of protein-like DOM. Increased bioavailability was
      associated with elevated extracellular enzyme activity of the initial microbial
      community supplied to samples during BDOC incubations. These findings indicate
      that changes in stream DOM quality due to watershed urbanization may impact
      stream ecosystem metabolism and ultimately the fate of organic carbon transported
      through fluvial systems. 

PMID- 24919114
TI  - Tissue engineering of a vascularized bone graft of critical size with an
      osteogenic and angiogenic factor-based in vivo bioreactor.
AB  - Engineering a large vascularized bone graft is a much greater challenge than
      engineering small bone tissues. Although this is essentially feasible through an
      osteogenic factor-based in vivo bioreactor technique, the ossification needs
      improving. This study was aimed to investigate the possibility and efficacy of
      ectopic cultivation of sizeable bone grafts with large angiogenic and osteogenic
      factor-loaded natural bovine bone mineral (NBBM) scaffolds. For this purpose, six
      groups of sizeable composite scaffolds were constructed, consisting of a titanium
      mesh cage of NBBM or a mixture of NBBM/autogenous bone particles (AB), which were
      preloaded with 660 MUg recombinant human bone morphogenetic protein-7 (rhBMP-7)
      and/or 4 MUg recombinant human vascular endothelial growth factor165 (rhVEGF165).
      The scaffolds were implanted in bilateral latissimus dorsi muscles in eight pigs
      to construct in vivo bioreactors. Sequential fluorescence labeling was then
      applied to trace bone formation at the early stage. The implants were retrieved
      12 weeks later. The undecalcified sections were observed in turn under the
      fluorescence microscope and light microscope to investigate early stage
      osteogenesis and histology. Moreover, new bone density (BD) was measured with
      histomorphometry. Compared with rhBMP-7-delivered NBBM scaffolds, rhVEGF165/rhBMP
      7-delivered NBBM scaffolds were with more intense intra-scaffold osteogenesis at
      the early stage and the ultimate sizeable bone grafts of microstructurally more
      lamellae and trabeculae, and quantitatively higher BD (31.93% vs. 22.37%,
      p<0.01). This study demonstrated that as for the endocultivation of a large bone
      graft with bioactive factor-based in vivo bioreactor technique, dual delivery of
      rhVEGF165/rhBMP-7 has synergic effects on improving early stage bone formation
      and subsequently bone quality and quantity of the bone grafts. 

PMID- 24919116
TI  - Groundnut bud necrosis virus encoded NSm associates with membranes via its C
      terminal domain.
AB  - Groundnut Bud Necrosis Virus (GBNV) is a tripartite ambisense RNA plant virus
      that belongs to serogroup IV of Tospovirus genus. Non-Structural protein-m (NSm),
      which functions as movement protein in tospoviruses, is encoded by the M RNA. In
      this communication, we demonstrate that despite the absence of any putative
      transmembrane domain, GBNV NSm associates with membranes when expressed in E.
      coli as well as in N. benthamiana. Incubation of refolded NSm with liposomes
      ranging in size from 200-250 nm resulted in changes in the secondary and tertiary
      structure of NSm. A similar behaviour was observed in the presence of anionic and
      zwitterionic detergents. Furthermore, the morphology of the liposomes was found
      to be modified in the presence of NSm. Deletion of coiled coil domain resulted in
      the inability of in planta expressed NSm to interact with membranes. Further,
      when the C-terminal coiled coil domain alone was expressed, it was found to be
      associated with membrane. These results demonstrate that NSm associates with
      membranes via the C-terminal coiled coil domain and such an association may be
      important for movement of viral RNA from cell to cell. 

PMID- 24919118
TI  - Solvatomagnetic Comparison Method: A Proper Quantification of Solvent Hydrogen
      Bond Basicity.
AB  - The hydrogen-bond-acceptor basicity of an important class of solvents, the
      amphiprotic solvents (water, alcohols, primary and secondary amides, and
      carboxylic acids), has not yet been properly parametrized. In this work, the
      first scale of solvent hydrogen-bond basicity applicable to amphiprotic solvents
      is established by means of a new method that compares the 19F NMR chemical shifts
      of 4-fluorophenol and 4-fluoroanisole in hydrogen-bond-acceptor solvents. This so
      called solvatomagnetic comparison method is free of the shortcomings of the
      solvatochromic comparison method used so far and is easier to carry out than the
      pure base calorimetric method. The validity of the new scale is assessed by good
      linear correlations with spectroscopic, thermodynamic, and kinetic solute
      properties depending on the solvent hydrogen-bond basicity. In such correlation
      analysis of solvent effects on physicochemical properties, solvent and solute
      hydrogen-bond basicity scales must not be mixed, since it is shown here that
      solute and solvent scales are not equivalent. A comprehensive collection of
      parameters quantifying the hydrogen-bond basicity is presented for 168 solvents.

PMID- 24919117
TI  - Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond
      differently to ultraviolet radiation: implications for retinal diseases.
AB  - BACKGROUND: It has been recognized that cells do not respond equally to
      ultraviolet (UV) radiation but it is not clear whether this is due to genetic,
      biochemical or structural differences of the cells. We have a novel cybrid
      (cytoplasmic hybrids) model that allows us to analyze the contribution of
      mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose
      of UV. mtDNA can be classified into haplogroups as defined by accumulations of
      specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J
      haplogroup is high risk for age-related macular degeneration while the H
      haplogroup is protective. This study investigates gene expression responses in J
      cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation.
      METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by fusing platelets isolated
      from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria
      free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours,
      treated with 10 mJ of UV-radiation and cultured for an additional 120 hours.
      Untreated and treated cybrids were analyzed for growth rates and gene expression
      profiles. The UV-treated and untreated J cybrids had higher growth rates compared
      to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH,
      CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV
      treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased
      CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids.
      CONCLUSION/SIGNIFICANCE: In cells with identical nuclei, the cellular response to
      sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This
      supports the hypothesis that differences in growth rates and expression levels of
      complement, inflammation and apoptosis genes may result from population-specific,
      hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage
      in tissues, the mtDNA haplogroup background may be important to consider.

PMID- 24919119
TI  - Sling exercise for chronic low back pain: a systematic review and meta-analysis.
AB  - BACKGROUND: Trials on sling exercise (SE), commonly performed to manage chronic
      low back pain (LBP), yield conflicting results. This study aimed to review the
      effects of SE on chronic LBP. METHODS: The randomized controlled trials comparing
      SE with other treatments or no treatment, published up to August 2013, were
      identified by electronic searches. Primary outcomes were pain, function, and
      return to work. The weighted mean difference (WMD) and 95% confidence interval
      (CI) were calculated, using a random-effects model. RESULTS: Risk of bias was
      rated as high in 9 included trials, where some important quality components such
      as blinding were absent and sample sizes were generally small. We found no
      clinically relevant differences in pain or function between SE and other forms of
      exercise, traditional Chinese medical therapy, or in addition to acupuncture.
      Based on two trials, SE was more effective than thermomagnetic therapy at
      reducing pain (short-term: WMD -13.90, 95% CI -22.19 to -5.62; long-term: WMD 
      26.20, 95% CI -31.32 to -21.08) and improving function (short-term: WMD -10.54,
      95% CI -14.32 to -6.75; long-term: WMD -25.75, 95% CI -30.79 to -20.71). In one
      trial we found statistically significant differences between SE and physical
      agents combined with drug therapy (meloxicam combined with eperisone
      hydrochloride) but of borderline clinical relevance for pain (short-term: WMD 
      15.00, 95% CI -19.64 to -10.36) and function (short-term: WMD -10.00; 95% CI 
      13.70 to -6.30). There was substantial heterogeneity among the two trials
      comparing SE and thermomagnetic therapy; both these trials and the trial
      comparing SE with physical agents combined with drug therapy had serious
      methodological limitations. INTERPRETATION: Based on limited evidence from 2
      trials, SE was more effective for LBP than thermomagnetic therapy. Clinically
      relevant differences in effects between SE and other forms of exercise, physical
      agents combined with drug therapy, traditional Chinese medical therapy, or in
      addition to acupuncture could not be found. More high-quality randomized trials
      on the topic are warranted.

PMID- 24919120
TI  - Identification of temozolomide resistance factors in glioblastoma via integrative
      miRNA/mRNA regulatory network analysis.
AB  - Drug resistance is a major issue in the treatment of glioblastoma. Almost all
      glioblastomas are intrinsically resistant to chemotherapeutic temozolomide (TMZ)
      or develop resistance during treatment. The interaction networks of microRNAs
      (miRNAs) and mRNAs likely regulate most biological processes and can be employed
      to better understand complex processes including drug resistance in cancer. In
      this study, we examined if integrative miRNA/mRNA network analysis using the web
      service tool mirConnX could be used to identify drug resistance factors in
      glioblastoma. We used TMZ-resistant glioblastoma cells and their integrated
      miRNA/mRNA networks to identify TMZ-sensitizing factors. TMZ resistance was
      previously induced in glioblastoma cell lines U87, Hs683, and LNZ308. miRNA/mRNA
      expression profiling of these cells and integration of the profiles using
      mirConnX resulted in the identification of plant homeodomain (PHD)-like finger 6
      (PHF6) as a potential TMZ-sensitizing factor in resistant glioblastoma cells.
      Analysis of PHF6 expression showed significant upregulation in glioblastoma as
      compared to normal tissue. Interference with PHF6 expression in three TMZ
      resistant subclones significantly enhanced TMZ-induced cell kill in two of these
      cell lines. Altogether, these results demonstrate that mirConnX is a feasible and
      useful tool to investigate miRNA/mRNA interactions in TMZ-resistant cells and has
      potential to identify drug resistance factors in glioblastoma. 

PMID- 24919122
TI  - Craniofrontonasal Syndrome: Atrial Septal Defect With a Novel EFNB1 Gene
      Mutation.
AB  - Craniofrontonasal syndrome (CFNS; OMIM # 304110) is a rare X-linked disorder with
      greater severity in heterozygous females than in hemizygous males. CFNS is
      characterized by coronal craniosynostosis, frontal bossing, severe hypertelorism,
      craniofacial asymmetry, downslant palpebral fissure, broad nasal root, bifid
      nasal tip, grooved fingernails, curly wiry hair, and abnormalities of the
      thoracic skeleton. There are very few cases describing association of CFNS with
      heart defects. We discuss a very rare feature: atrial septal defect in a
      molecularly confirmed case of CFNS. 

PMID- 24919121
TI  - Kindler syndrome in mice and men.
AB  - Kindler syndrome (KS) in humans is a severe skin blistering disease associated
      with inflammation and increased risk of epidermal squamous cell carcinoma (SCC).
      This disease is known to be caused by loss-of-function mutations in Kindlin-1, a
      focal adhesion beta-integrin binding protein. Thus far, it has been unclear what
      specific signaling events occur in KS keratinocytes to promote tumorigenesis,
      especially since loss of beta-integrins and focal adhesion complexes has been
      previously shown to prevent or delay tumor formation. In the April issue of
      Nature Medicine, Rognoni and colleagues generate a transgenic mouse lacking
      Kindlin-1 in the epidermis to model the key features of KS, and show that Kindlin
      1 regulates Wnt and TGFbeta signaling independent of beta-integrins. These beta1
      integrin-independent functions of Kindlin-1 may contribute to the increased SCC
      risk in KS patients. 

PMID- 24919123
TI  - Micro-structured Beta-Tricalcium Phosphate for Repair of the Alveolar Cleft in
      Cleft Lip and Palate Patients: A Pilot Study.
AB  - OBJECTIVES: Can a synthetic bone substitute be used to repair the alveolar cleft
      to bypass donor site morbidity as well as to shorten the operating time? In
      earlier experimental studies, micro-structured beta-tricalcium phosphate (beta
      TCP) provided similar bone healing when compared with grafting with iliac crest
      bone. This justifies the clinical evaluation of this bone substitute in the human
      alveolar cleft situation. DESIGN: Prospective clinical study. SETTING: University
      clinic. PARTICIPANTS: Seven patients, all with unilateral alveolar cleft, were
      randomly included for alveolar cleft repair with beta-TCP in 2010 and 2011. MAIN
      OUTCOME MEASURES: In all patients, the alveolar cleft was repaired by micro
      structured beta-TCP grafting. Our assessments were distilled from cone beam
      computed tomography scans taken preoperatively, 1 week postoperatively, and 6
      months postoperatively. A volumetric outcome could be realized. RESULTS: Six
      months after the operative grafting of micro-structured beta-TCP into the
      alveolar cleft, the bone volume thus acquired was satisfactory. We found an
      average bone volume percentage of 73% +/- 6% compared with the original cleft
      volume. CONCLUSIONS: Previous experimental and clinical studies and the initial
      findings of this pilot study now elucidate a path toward the clinical use of
      micro-structured beta-TCP bone substitute for repair of the alveolar cleft.

PMID- 24919124
TI  - Evaluation of Stress Distribution of Mini Dental Implant-Supported Overdentures
      in Complete Cleft Palate Models: A Three-Dimensional Finite Element Analysis
      Study.
AB  - OBJECTIVE: Mini dental implants could be an alternative treatment method for
      prosthetic treatment of edentulous cleft palate. The aim of this study was to
      analyze stress distribution around the cortical bone and different plans using a
      varied number of mini dental implants in edentulous unilateral complete cleft
      palates. MATERIALS AND METHODS: Three edentulous maxillary models were modified
      to create unilateral complete cleft palates. Mini dental implants (2.4 * 15 mm)
      were located as two mini implants at the premolar region, four mini implants at
      the premolar and molar region, and six mini implants at the first premolar,
      second premolar, and first molar regions in the models, respectively. Mucosa, o
      ring/ball attachments, and overdentures were simulated. Vertical and horizontal
      loads of 100 N were applied on both the right and left molar teeth of the
      overdenture for each model. Maximum and minimum principal stress values and the
      distribution at cortical bone around the implants and cleft palates were
      evaluated by finite element analysis. RESULTS: Stress values under vertical loads
      were lower than values under horizontal loadings for all models. Stress values
      were found to be lower in the first model than in the second and third models.
      The highest stress values were found around implants in the second model. The
      unilateral feature of a complete cleft pattern affected the stress distribution.
      CONCLUSION: Stresses occured mostly around implants when the overdenture was
      supported by six implants; however, the stress distribution around implants was
      low with two implants because of tissue support.

PMID- 24919125
TI  - Evaluation of Transverse Maxillary Expansion After a Segmental Posterior
      Subapical Maxillary Osteotomy in Cleft Lip and Palate Patients With Severe
      Collapse of the Lateral Maxillary Segments.
AB  - Objective :  The purpose of this longitudinal retrospective study was to evaluate
      transverse maxillary expansion after a Schuchardt or segmental posterior
      subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate
      (CLP). A second aim was to compare these data with data for adult patients
      without CLP who were receiving a surgical assisted rapid palatal expansion
      (SARPE). Method :  The study group comprised 19 patients with CLP and a severe
      transversally collapsed maxilla who were treated with SPSMO followed by hyrax
      expansion at the University Hospitals Leuven. Dental casts of the 19 patients
      were analyzed before treatment, at maximum expansion, during orthodontic
      treatment, at the completion of orthodontic treatment. and 2 years after
      orthodontic treatment and were measured at the canine, premolar, and molar
      levels. Adult patients without CLP who were enrolled in a prospective study
      served as the control group. Results :  Maxillary expansion within the study
      group was significantly greater (P < .05) at all measured levels compared with
      the maxillary arch before treatment. No significant relapse was measured in the
      study group 2 years after orthodontic treatment. When comparing the study and
      control groups, the only statistical difference was that canine expansion was
      significantly greater in the study group. Conclusion :  SPSMO followed by
      maxillary expansion and orthodontic treatment is an appropriate treatment option
      to correct a severe transversally collapsed maxilla in patients with CLP. The
      overall treatment effect of SPSMO expansion is comparable with the effects of
      SARPE, although canine expansion was greater in the SPSMO group.

PMID- 24919126
TI  - Functional and aesthetic rehabilitation of a geriatric patient with cleft palate:
      a case report.
AB  - Cleft palate defect with complete edentulism in elderly patients presents a
      prosthodontic challenge for complete denture fabrication. Such large defects are
      very difficult to restore by surgical intervention and have direct consequence on
      such functions as mastication and speech, on aesthetics, and on the patient's
      mental attitude. This article describes a case report in which a 76-year-old
      female patient underwent restoration with a closed hollow bulb obturator for a
      large cleft palate defect.

PMID- 24919127
TI  - A clinical multicenter study of orofacial features in 26 brazilian patients with
      different types of mucopolysaccharidosis.
AB  - PURPOSE: This study aimed to describe the orofacial features of 26 unrelated
      Brazilian patients with mucopolysaccharidosis and to verify any possible
      associations between these findings and specific types of mucopolysaccharidosis.
      METHODS: Patients were diagnosed with mucopolysaccharidosis and clinically
      evaluated. Following consent, a clinical assessment form was completed. Facial
      and intraoral examination was performed by evaluating facial pattern,
      malocclusions, dental caries, and tooth identification. RESULTS: Midface
      deficiency, increased lower facial third, anterior open bite, convex profile,
      macroglossia, gingival enlargement, and spaced arches were the most frequently
      observed features. These findings did not allow a differential diagnosis among
      the different types of mucopolysaccharidosis, except for pitting enamel, which
      significantly associated with mucopolysaccharidosis IVA (P < .001). Open bite was
      associated with mucopolysaccharidosis types I, II, III, and VI; however, only one
      patient with mucopolysaccharidosis IVA expressed this feature (P = .043).
      CONCLUSIONS: Our results suggest that pitted enamel in patients with
      mucopolysaccharidosis is most likely a feature of mucopolysaccharidosis type IVA;
      whereas, open bite is rarely observed in these patients. Orofacial features in
      mucopolysaccharidosis may help pediatric dentists recognize this disorder and
      minimize the delay between the initial signs/symptoms and diagnosis of the
      disease. Future studies should focus on the longitudinal manifestations,
      expression, and severity of mucopolysaccharidosis-associated orofacial anomalies.

PMID- 24919128
TI  - Nutcrackerlike Phenomenon Is An Unusual Cause for Gross Hematuria After a Kidney
      Graft.
AB  - Nutcracker phenomenon is the condition that occurs most commonly at the
      morphologic type by compression of the left renal vein between the aorta and
      superior mesenteric artery. The diagnosis is often delayed because of the
      variability in manifestations and absence of consensus on diagnostic criteria. We
      report a 30-year-old woman who presented gross hematuria several days after a
      kidney transplant. Nutcracker syndrome was established intraoperatively during
      open surgical approach for bladder clot evacuation. Renal repositioning was done
      with relief in the degree of hematuria intraoperatively. No episode of gross
      hematuria was observed on follow-up after 8 months. 

PMID- 24919129
TI  - Identification and assessment of potential water quality impact factors for
      drinking-water reservoirs.
AB  - Various reservoirs have been serving as the most important drinking water sources
      in Zhejiang Province, China, due to the uneven distribution of precipitation and
      severe river pollution. Unfortunately, rapid urbanization and industrialization
      have been continuously challenging the water quality of the drinking-water
      reservoirs. The identification and assessment of potential impacts is
      indispensable in water resource management and protection. This study
      investigates the drinking water reservoirs in Zhejiang Province to better
      understand the potential impact on water quality. Altogether seventy-three
      typical drinking reservoirs in Zhejiang Province encompassing various water
      storage levels were selected and evaluated. Using fifty-two reservoirs as
      training samples, the classification and regression tree (CART) method and
      sixteen comprehensive variables, including six sub-sets (land use, population,
      socio-economy, geographical features, inherent characteristics, and climate),
      were adopted to establish a decision-making model for identifying and assessing
      their potential impacts on drinking-water quality. The water quality class of the
      remaining twenty-one reservoirs was then predicted and tested based on the
      decision-making model, resulting in a water quality class attribution accuracy of
      81.0%. Based on the decision rules and quantitative importance of the independent
      variables, industrial emissions was identified as the most important factor
      influencing the water quality of reservoirs; land use and human habitation also
      had a substantial impact on water quality. The results of this study provide
      insights into the factors impacting the water quality of reservoirs as well as
      basic information for protecting reservoir water resources. 

PMID- 24919130
TI  - Effort-reward imbalance at school and depressive symptoms in Chinese adolescents:
      the role of family socioeconomic status.
AB  - Depression is a major mental health problem during adolescence. This study, using
      a sample of Chinese adolescents, examined the separate and combined effects of
      perceived school-related stress and of family socioeconomic status (SES) on the
      prevalence of depressive symptoms. A total of 1774 Chinese students from Grades 7
      12 were recruited into our questionnaire survey. School-related stress was
      measured by the Effort-Reward Imbalance Questionnaire-School Version, family SES
      was assessed by a standardized question, and depressive symptoms were evaluated
      by the Center for Epidemiological Studies Depression Scale for Children.
      Multivariate logistic regression was applied, adjusting for age, gender, grade,
      smoking, alcohol drinking and physical activity. It was found that high school
      related stress and low family SES were associated with elevated odds of
      depressive symptoms, respectively. The effect of school-related stress was
      particularly strong in low SES group. In adolescents with both high stress at
      school and low SES, the odds ratio was 9.18 (95% confidence interval = 6.53
      12.89) compared to the reference group (low stress at school and high SES). A
      significant synergistic interaction effect was observed (synergy index = 2.28,
      95% confidence interval = 1.56-3.32). The findings indicated that perceived
      school-related stress, in terms of effort-reward imbalance, was related to
      depressive symptoms in this sample of Chinese adolescents. The strong interaction
      with family SES suggests that health promoting efforts in school settings should
      be targeted specifically at these socially deprived groups. 

PMID- 24919132
TI  - Water quality of a reservoir and its major tributary located in east-central
      Mexico.
AB  - A reservoir with ecological and economic importance and its major tributary,
      localized in east-central Mexico, were studied. The aim of this work was to know
      the physicochemical water characteristics of both water bodies and to contrast
      these by their different uses, and also estimate overall water quality using a
      Water Quality Index (WQI). Water samples from the reservoir and the tributary
      were obtained in different climatic seasons. In the tributary, anoxic and hypoxic
      conditions and high levels of organic matter, orthophosphate, and ammonium showed
      that this is strongly impacted by wastewater discharges and that the water is not
      suitable for different uses; independently of the season, the WQI showed "poor"
      quality (34.4-47.2). In contrast, in the reservoir a better water quality was
      determined; the WQI in the sampling months ranged from 72.1-76.6 ("good"
      quality), and spatially, this was from 66.5-79.5 ("fair" and "good" quality). 

PMID- 24919131
TI  - Biosorption of strontium from simulated nuclear wastewater by Scenedesmus
      spinosus under culture conditions: adsorption and bioaccumulation processes and
      models.
AB  - Algae biosorption is an ideal wastewater treatment method when coupled with algae
      growth and biosorption. The adsorption and bioaccumulation of strontium from
      simulated nuclear wastewater by Scenedesmus spinosus were investigated in this
      research. One hundred mL of cultured S. spinosus cells with a dry weight of 1.0
      mg in simulated nuclear wastewater were used to analyze the effects on S.
      spinosus cell growth as well as the adsorption and bioaccumulation characters
      under conditions of 25 +/- 1  degrees C with approximately 3,000 lux
      illumination. The results showed that S. spinosus had a highly selective
      biosorption capacity for strontium, with a maximum bioremoval ratio of 76%. The
      adsorbed strontium ion on cell walls was approximately 90% of the total adsorbed
      amount; the bioaccumulation in the cytoplasm varied by approximately 10%. The
      adsorption quantity could be described with an equilibrium isotherm. The pseudo
      second-order kinetic model suggested that adsorption was the rate-limiting step
      of the biosorption process. A new bioaccumulation model with three parameters was
      proposed and could give a good fit with the experiment data. The results
      suggested that S. spinosus may be a potential biosorbent for the treatment of
      nuclear wastewater in culture conditions.

PMID- 24919133
TI  - Functional and radiographic outcomes of unstable juvenile osteochondritis
      dissecans of the knee treated with lesion fixation using bioabsorbable pins.
AB  - BACKGROUND: The purpose of this study was to evaluate the functional and
      radiographic outcome of fixation of unstable juvenile osteochondritis dissecans
      lesions of the knee after a minimum of 2 years of follow-up. METHODS: A total of
      33 unstable juvenile osteochondritis dissecans lesions in 30 patients underwent
      fixation using bioabsorbable pins through arthrotomy or under arthroscopy. The
      patients consisted of 23 males and 7 females, and the average age at the time of
      operation was 14.4 years (range, 11 to 17 y). The functional outcomes were
      evaluated using the Lysholm score and Hughston's criteria at a mean follow-up of
      3.3 years (range, 2.1 to 6.3 y). Healing of the osteochondritis dissecans lesions
      were confirmed by plain radiographs and magnetic resonance imaging. RESULTS: The
      Lysholm score improved significantly at 3 months after the surgery, and was
      maintained until the final follow-up. Radiographically, 32 of 33 lesions healed
      after fixation of the lesion (healing rate was 97.0%). Healing was achieved at an
      average of 2.4 months on plain radiographs and 4.2 months on magnetic resonance
      imaging. According to Hughston's criteria, 25 patients were graded as excellent,
      4 as good, and 1 as poor at the final follow-up. CONCLUSIONS: The fixation of the
      unstable juvenile osteochondritis dissecans lesions with bioabsorbable pins
      demonstrated improved clinical outcomes and radiographic high healing rates at a
      mean of 3.3 years of follow-up. We advocate this procedure for patients with
      unstable juvenile osteochondritis dissecans lesions of sufficient quality to
      enable fixation which will preserve the normal contour of the distal femur. LEVEL
      OF EVIDENCE: Level IV-retrospective case series.

PMID- 24919134
TI  - Classifying cerebral palsy: are we nearly there?
AB  - BACKGROUND: Cerebral palsy (CP) is the most common cause of physical disability
      in childhood in developed countries and encompasses a wide range of clinical
      phenotypes. Classification of CP according to movement disorder or topographical
      distribution is widely used. However, these classifications are not reliable nor
      do they accurately predict musculoskeletal pathology. More recently, the Gross
      Motor Function Classification System (GMFCS) has been introduced and its
      validity, reliability, and clinical utility have been confirmed. In 2005 it was
      suggested that children should be described and classified according to the GMFCS
      in all outcome studies involving children with CP, in the Journal of Pediatric
      Orthopaedics (JPO). This study aimed to describe utilization of the GMFCS in 3
      journals: Journal of Bone and Joint Surgery (JBJS Am), JPO, and Developmental
      Medicine and Child Neurology (DMCN), over a 7-year period (2005 to 2011), and any
      relationship to the journal's impact factor. A secondary aim was to establish if
      differences in methodological quality existed between those studies utilizing
      GMFCS and those that did not. METHODS: A targeted literature search of the 3
      selected journals using the term "cerebral palsy" was conducted using the Medline
      database. Utilization of the GMFCS was assessed using report of these data in the
      methods or results section of the retrieved papers. The Methodological Index for
      Non-Randomized Studies (MINORS) was employed to evaluate the quality of papers
      published in JPO. RESULTS: One hundred and fifty-four studies met the inclusion
      criteria and in 85 (68%) the GMFCS was used. Of these, 112 were published in JPO,
      of which 51 (46%) utilized the GMFCS, compared with 72% for JBJS Am, and 88% for
      DMCN. In the JPO, utilization of the GMFCS improved from 13% to 80%, over the 7
      year study period. CONCLUSIONS: Utilization of the GMFCS has increased rapidly
      over the past 7 years in the JPO but there is room for further improvement. LEVEL
      OF EVIDENCE: Not applicable.

PMID- 24919135
TI  - Neurological and vascular injury associated with supracondylar humerus fractures
      and ipsilateral forearm fractures in children.
AB  - BACKGROUND: Approximately 5% of supracondylar humerus fractures in children are
      associated with an ipsilateral forearm fracture, often referred to as a floating
      elbow when both injuries are displaced. Historically, these patients have higher
      complication rates than patients with an isolated supracondylar humerus fracture.
      The purpose of this study was to review the acute neurologic and vascular
      injuries in patients with ipsilateral, operative supracondylar humerus and
      forearm fractures and compare the findings with a cohort of isolated, operative
      supracondylar humerus fractures. METHODS: We performed an IRB-approved,
      retrospective review of all pediatric patients with ipsilateral, operative
      supracondylar humerus and forearm fractures from a single institution and
      compared our findings to a cohort of isolated, operative supracondylar humerus
      fractures. RESULTS: A total of 150 patients with operative supracondylar humerus
      and ipsilateral forearm fractures were compared with 1228 patients with isolated,
      operative supracondylar humerus fractures. Twenty-two of the 150 (14.7%) floating
      elbow patients had documented pretreatment nerve palsies compared with 96/1228
      (7.8%) of isolated injury patients (P=0.006). Eighteen of 22 nerve palsies were
      in patients with forearm fractures that required reduction. The overall incidence
      of nerve palsy was 18.9% (18/95) when a forearm fracture required reduction
      compared with only 7.3% (4/55) in a forearm fracture that was not reduced
      (P=0.05). We did not find a significant difference in the rate of pulseless
      extremities when comparing the ipsilateral (6/150 4%) and isolated (50/1228 4.1%)
      injury patients. No compartment syndromes were identified in any patient with an
      ipsilateral injury. CONCLUSIONS: The rate of acute neurologic injury in
      ipsilateral supracondylar humerus and forearm fractures is almost twice than that
      found in patients with isolated supracondylar humerus fractures. This rate
      increases further when the forearm fracture requires a manipulative reduction.
      The likelihood of a pulseless extremity was not dependent upon the presence of a
      forearm injury in our study. The presence of an ipsilateral forearm fracture
      should alert the surgeon to carefully assess the preoperative neurovascular
      status of patients with supracondylar humerus injuries. LEVEL OF EVIDENCE: Level
      III.

PMID- 24919136
TI  - Proximal migration of femoral telescopic rod in children with osteogenesis
      imperfecta.
AB  - BACKGROUND: Intramedullary telescopic rod fixation has been used for
      stabilization of the long bones in growing children who have osteogenesis
      imperfecta. Proximal migration of the rod is the most common complication of
      telescopic rodding in the femur. The purposes of this study were to evaluate
      incidence and temporal pattern of proximal migration of the femoral rod, and to
      investigate factors related to it. METHODS: A total of 50 patients with
      osteogenesis imperfecta, who had femur stabilized by telescopic rod with T-piece,
      were the subjects of this study. In patients having both the femora stabilized,
      only 1 femur was randomly selected for analysis. Hence, in 50 femora, migration
      free survivorship was analyzed using the Kaplan-Meier method, and association
      with possible risk factors was analyzed by Cox regression analysis using the
      proportional hazards model. Factors investigated in the analysis include age at
      the time of surgery, sex, purpose of the index surgery, residual or developing
      angular deformity of the femur, rod position at the distal physis, persistent
      cortical gap at fracture/osteotomy site, Sillence classification, and type of
      telescopic rod. RESULTS: Proximal migration was observed in 7 of 50 femora.
      Cumulative survival without proximal migration was 0.94 (95% CI, 0.87-1.01) in 1
      year, and 0.85 (95% CI, 0.75-0.95) in 6 years. Factors significantly associated
      with proximal rod migration in Kaplan-Meier survivorship analysis and univariate
      Cox regression analysis were angular deformity, eccentric rod position at the
      distal physis, and persistent cortical gap. When these factors were analyzed by
      multivariate analysis, eccentric rod position at the distal physis was the only
      significant factor with a hazard ratio of 11.74. CONCLUSIONS: The risk of
      proximal rod migration can be reduced by complete correction of angular deformity
      and optimal placement of the rod at the distal physis. Our data also suggest that
      developing angular deformity or persistent osteotomy/fracture gap requires
      special attention at the possibility of proximal rod migration during follow-up.
      LEVEL OF EVIDENCE: Level III, prognostic study.

PMID- 24919137
TI  - The cross-table lateral radiograph results in a significantly increased effective
      radiation dose compared with the Dunn and single frog lateral radiographs.
AB  - BACKGROUND: A lateral radiograph of the proximal femur is critical in the
      evaluation of patients with suspected femoroacetabular impingement. Positioning
      patients for a cross-table lateral (XTL) image is difficult, which may result in
      repeat exposures and increased cumulative radiation. Alternatively, the 45-degree
      Dunn (Dunn) and single frog lateral (SFL) views have been shown to accurately
      reveal proximal femoral abnormalities in femoroacetabular impingement. The
      purpose of this study was to compare the effective radiation doses (ERD) for 3
      lateral hip projections that provide similar diagnostic information. METHODS:
      Patients presenting to the adolescent hip clinic with indicated examinations were
      evaluated with a standard anteroposterior (AP) pelvic radiograph and one of 3
      lateral hip radiographs: XTL (n=16), Dunn (n=17), or SFL (n=27). Technical
      exposure parameters and published reference data for an AP pelvic radiograph were
      used to extrapolate the ERD. A simple Pearson r correlation test determined the
      relationships between body mass index, age, and ERD. The rate of repeat exposures
      per study was calculated. RESULTS: Body mass index positively correlated (r=0.34)
      and age and negatively correlated (r=-0.27) with ERD. ERD was increased for the
      XTL (0.83+/-0.98 mSv) over the Dunn (0.37+/-0.15 mSv) and SFL (0.22+/-0.11 mSv;
      P<0.05). Repeat exposures were performed in 10.4%, 4%, and 6% of XTL, Dunn, and
      SFL studies, respectively. CONCLUSIONS: The ERD for a single projection is
      highest for the XTL, and the examination is more likely to be repeated. The XTL
      radiograph should be avoided whenever possible and substituted with alternative
      images providing similar diagnostic information, such as the Dunn or SFL, to
      minimize lifetime cumulative radiation exposure to the patient. LEVEL OF
      EVIDENCE: Level II.

PMID- 24919138
TI  - Long-finger pollicization for macrodactyly of the thumb and index finger.
AB  - Pollicization of the long finger is rarely performed, and previously described
      for treating traumatic thumb and index finger loss. Because the long finger lacks
      the independence of motion and muscular attachments of the index finger,
      pollicization of the long finger requires modifications of the technique. We
      present the case of a 3-year-old girl with progressive macrodactyly of the thumb
      and index finger associated with a lipofibromatous hamartoma of the median nerve.
      The involved digits were severely enlarged, stiff, and nonfunctional. The child
      was treated with first and second ray resection followed by long-finger
      pollicization. Surgical pearls and pitfalls are discussed. 

PMID- 24919139
TI  - Stability properties of an ancient plant peroxidase.
AB  - Plant (Class III) peroxidases have numerous applications throughout biotechnology
      but their thermal and oxidative stabilities may limit their usefulness.
      Horseradish peroxidase isoenzyme C (HRPC) has good catalytic turnover and is
      moderately resistant to heat and to excess (oxidizing) concentrations of hydrogen
      peroxide. In contrast, HRP isoenzyme A2 (HRP A2) has better oxidative but poorer
      thermal stability, while soybean peroxidase (SBP) displays enhanced thermal
      stability. Intrigued by these variations amongst closely related enzymes, we
      previously used maximum likelihood methods (with application of Bayesian
      statistics) to infer an amino acid sequence consistent with their most recent
      common ancestor, the 'Grandparent' (GP). Here, we report the cloning and
      expression of active recombinant GP protein in Escherichia coli. GP's half
      inactivation temperature was 45  degrees C, notably less than HRP C's, but its
      resistance to excess H2O2 was 2-fold greater. This resurrected GP protein enables
      a greater understanding of plant peroxidase evolution and serves as a test-bed to
      explore their ancestral properties. 

PMID- 24919140
TI  - Rational design, preparation, and characterization of a therapeutic enzyme mutant
      with improved stability and function for cocaine detoxification.
AB  - Cocaine esterase (CocE) is known as the most efficient natural enzyme for cocaine
      hydrolysis. The major obstacle to the clinical application of wild-type CocE is
      the thermoinstability with a half-life of only ~12 min at 37  degrees C. The
      previously designed T172R/G173Q mutant (denoted as enzyme E172-173) with an
      improved in vitro half-life of ~6 h at 37  degrees C is currently in clinical
      trial Phase II for cocaine overdose treatment. Through molecular modeling and
      dynamics simulation, we designed and characterized a promising new mutant of E172
      173 with extra L196C/I301C mutations (denoted as enzyme E196-301) to produce
      cross-subunit disulfide bonds that stabilize the dimer structure. The cross
      subunit disulfide bonds were confirmed by X-ray diffraction. The designed
      L196C/I301C mutations have not only considerably extended the in vitro half-life
      at 37  degrees C to >100 days, but also significantly improved the catalytic
      efficiency against cocaine by ~150%. In addition, the thermostable E196-301 can
      be PEGylated to significantly prolong the residence time in mice. The PEGylated
      E196-301 can fully protect mice from a lethal dose of cocaine (180 mg/kg, LD100)
      for at least 3 days, with an average protection time of ~94h. This is the longest
      in vivo protection of mice from the lethal dose of cocaine demonstrated within
      all studies using an exogenous enzyme reported so far. Hence, E196-301 may be
      developed to become a more valuable therapeutic enzyme for cocaine abuse
      treatment, and it demonstrates that a general design strategy and protocol to
      simultaneously improve both the stability and function are feasible for rational
      protein drug design. 

PMID- 24919142
TI  - Tunable temperature-responsive supramolecular hydrogels formed by prodrugs as a
      codelivery system.
AB  - Taking advantage of the strong hydrophobicity of the anticancer drug camptothecin
      (CPT), the CPT molecule was conjugated to a class of low-molecular-weight (MW)
      poly(ethylene glycol) (PEG) chains (MW = 500, 1000, and 2000), forming an
      amphiphilic prodrug. The CPT-PEG prodrug formed stable hydrogels based on a
      combination of the partial inclusion complexation between one end of the PEG
      blocks and alpha-CD and the hydrophobic aggregation of CPT groups. Meanwhile, the
      formed hydrogels could be loaded with water-soluble drug 5-fluorouracil (5-FU),
      which is always combined with CPT drugs to enhance their anticancer activity.
      Moreover, the hydrogel systems demonstrate unique structure-related reversible
      gel-sol transition properties at a certain temperature due to the reversible
      supramolecular assembly, and the gel-sol transition temperature could be
      modulated by varying the length of the PEG chain and the concentrations of alpha
      CD, demonstrating the possibility of achieving on-demand gel-sol transitions. The
      structure-related reversible gel-sol transition properties were proved by
      rheological property, XRD, DSC, and SEM measurements. The different controlled
      release profiles of two different anticancer drugs showed significant temperature
      dependent properties. This easily prepared supramolecular hydrogel with excellent
      biocompatibility and tunable temperature responsiveness has significant potential
      for controlled drug release applications. 

PMID- 24919141
TI  - High-spin ferric ions in Saccharomyces cerevisiae vacuoles are reduced to the
      ferrous state during adenine-precursor detoxification.
AB  - The majority of Fe in Fe-replete yeast cells is located in vacuoles. These acidic
      organelles store Fe for use under Fe-deficient conditions and they sequester it
      from other parts of the cell to avoid Fe-associated toxicity. Vacuolar Fe is
      predominantly in the form of one or more magnetically isolated nonheme high-spin
      (NHHS) Fe(III) complexes with polyphosphate-related ligands. Some Fe(III)
      oxyhydroxide nanoparticles may also be present in these organelles, perhaps in
      equilibrium with the NHHS Fe(III). Little is known regarding the chemical
      properties of vacuolar Fe. When grown on adenine-deficient medium (A?), ADE2Delta
      strains of yeast such as W303 produce a toxic intermediate in the adenine
      biosynthetic pathway. This intermediate is conjugated with glutathione and
      shuttled into the vacuole for detoxification. The iron content of A? W303 cells
      was determined by Mossbauer and EPR spectroscopies. As they transitioned from
      exponential growth to stationary state, A? cells (supplemented with 40 MUM
      Fe(III) citrate) accumulated two major NHHS Fe(II) species as the vacuolar NHHS
      Fe(III) species declined. This is evidence that vacuoles in A? cells are more
      reducing than those in adenine-sufficient cells. A? cells suffered less oxidative
      stress despite the abundance of NHHS Fe(II) complexes; such species typically
      promote Fenton chemistry. Most Fe in cells grown for 5 days with extra yeast
      nitrogen-base, amino acids and bases in minimal medium was HS Fe(III) with
      insignificant amounts of nanoparticles. The vacuoles of these cells might be more
      acidic than normal and can accommodate high concentrations of HS Fe(III) species.
      Glucose levels and rapamycin (affecting the TOR system) affected cellular Fe
      content. This study illustrates the sensitivity of cellular Fe to changes in
      metabolism, redox state and pH. Such effects broaden our understanding of how Fe
      and overall cellular metabolism are integrated. 

PMID- 24919143
TI  - AgSbF6-controlled diastereodivergence in alkyne hydroarylation: facile access to
      Z- and E-alkenyl arenes.
AB  - AgSbF6-controlled diastereodivergent hydroarylation reactions were developed.
      Unprecedented and remarkable switching of the E/Z-stereoselectivity could be
      obtained by adjusting the AgSbF6 loading. 

PMID- 24919144
TI  - Combined administration of antibiotics and direct oral anticoagulants: a renewed
      indication for laboratory monitoring?
AB  - The recent development and marketing of novel direct oral anticoagulants (DOACs)
      represents a paradigm shift in the management of patients requiring long-term
      anticoagulation. The advantages of these compounds over traditional therapy with
      vitamin K antagonists include a reportedly lower risk of severe hemorrhages and
      the limited need for laboratory measurements. However, there are several
      scenarios in which testing should be applied. The potential for drug-to-drug
      interaction is one plausible but currently underrecognized indication for
      laboratory assessment of the anticoagulant effect of DOACs. In particular,
      substantial concern has been raised during Phase I studies regarding the
      potential interaction of these drugs with some antibiotics, especially those that
      interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A
      specific electronic search on clinical trials published so far confirms that
      clarithromycin and rifampicin significantly impair the bioavailability of
      dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole
      alter the metabolism of rivaroxaban in vivo. Because of their more recent
      development, no published data were found for apixaban and edoxaban, or for
      potential interactions of DOACs with other and widely used antibiotics. It is
      noteworthy, however, that an online resource based on Food and Drug
      Administration and social media information, reports several hemorrhagic and
      thrombotic events in patients simultaneously taking dabigatran and some commonly
      used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According
      to these reports, the administration of antibiotics in patients undergoing
      therapy with DOACs would seem to require accurate evaluation as to whether dose
      adjustments (personalized or antibiotic class driven) of the anticoagulant drug
      may be advisable. This might be facilitated by direct laboratory assessments of
      their anticoagulant effect ex vivo. 

PMID- 24919145
TI  - Structural biology: wobble puts RNA on target.

PMID- 24919146
TI  - A primitive fish from the Cambrian of North America.
AB  - Knowledge of the early evolution of fish largely depends on soft-bodied material
      from the Lower (Series 2) Cambrian period of South China. Owing to the rarity of
      some of these forms and a general lack of comparative material from other
      deposits, interpretations of various features remain controversial, as do their
      wider relationships amongst post-Cambrian early un-skeletonized jawless
      vertebrates. Here we redescribe Metaspriggina on the basis of new material from
      the Burgess Shale and exceptionally preserved material collected near Marble
      Canyon, British Columbia, and three other Cambrian Burgess Shale-type deposits
      from Laurentia. This primitive fish displays unambiguous vertebrate features: a
      notochord, a pair of prominent camera-type eyes, paired nasal sacs, possible
      cranium and arcualia, W-shaped myomeres, and a post-anal tail. A striking feature
      is the branchial area with an array of bipartite bars. Apart from the anterior
      most bar, which appears to be slightly thicker, each is associated with
      externally located gills, possibly housed in pouches. Phylogenetic analysis
      places Metaspriggina as a basal vertebrate, apparently close to the Chengjiang
      taxa Haikouichthys and Myllokunmingia, demonstrating also that this primitive
      group of fish was cosmopolitan during Lower-Middle Cambrian times (Series 2-3).
      However, the arrangement of the branchial region in Metaspriggina has wider
      implications for reconstructing the morphology of the primitive vertebrate. Each
      bipartite bar is identified as being respectively equivalent to an epibranchial
      and ceratobranchial. This configuration suggests that a bipartite arrangement is
      primitive and reinforces the view that the branchial basket of lampreys is
      probably derived. Other features of Metaspriggina, including the external
      position of the gills and possible absence of a gill opposite the more robust
      anterior-most bar, are characteristic of gnathostomes and so may be primitive
      within vertebrates. 

PMID- 24919147
TI  - The genome of Eucalyptus grandis.
AB  - Eucalypts are the world's most widely planted hardwood trees. Their outstanding
      diversity, adaptability and growth have made them a global renewable resource of
      fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of
      Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem
      duplications, the largest proportion thus far in plant genomes. Eucalyptus also
      shows the highest diversity of genes for specialized metabolites such as terpenes
      that act as chemical defence and provide unique pharmaceutical oils. Genome
      sequencing of the E. grandis sister species E. globulus and a set of inbred E.
      grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding
      depression. The E. grandis genome is the first reference for the eudicot order
      Myrtales and is placed here sister to the eurosids. This resource expands our
      understanding of the unique biology of large woody perennials and provides a
      powerful tool to accelerate comparative biology, breeding and biotechnology. 

PMID- 24919148
TI  - The selective tRNA aminoacylation mechanism based on a single G*U pair.
AB  - Ligation of tRNAs with their cognate amino acids, by aminoacyl-tRNA synthetases,
      establishes the genetic code. Throughout evolution, tRNA(Ala) selection by alanyl
      tRNA synthetase (AlaRS) has depended predominantly on a single wobble base pair
      in the acceptor stem, G3*U70, mainly on the kcat level. Here we report the
      crystal structures of an archaeal AlaRS in complex with tRNA(Ala) with G3*U70 and
      its A3*U70 variant. AlaRS interacts with both the minor- and the major-groove
      sides of G3*U70, widening the major groove. The geometry difference between
      G3*U70 and A3*U70 is transmitted along the acceptor stem to the 3'-CCA region.
      Thus, the 3'-CCA region of tRNA(Ala) with G3*U70 is oriented to the reactive
      route that reaches the active site, whereas that of the A3*U70 variant is folded
      back into the non-reactive route. This novel mechanism enables the single wobble
      pair to dominantly determine the specificity of tRNA selection, by an approximate
      100-fold difference in kcat. 

PMID- 24919150
TI  - Cancer: natural-born killers unleashed.

PMID- 24919149
TI  - Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin
      inflammasome.
AB  - Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR)
      defend against pathogen infection by activating caspase 1. Pyrin, a candidate
      PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating
      complex. Mutations in the Pyrin-encoding gene, MEFV, cause a human
      autoinflammatory disease known as familial Mediterranean fever. Despite important
      roles in immunity and disease, the physiological function of Pyrin remains
      unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in
      response to Rho-glucosylation activity of cytotoxin TcdB, a major virulence
      factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea.
      The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating
      activity. Other Rho-inactivating toxins, including FIC-domain
      adenylyltransferases (Vibrio parahaemolyticus VopS and Histophilus somni IbpA)
      and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically
      activate the Pyrin inflammasome in their enzymatic activity-dependent manner.
      These toxins all target the Rho subfamily and modify a switch-I residue. We
      further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating
      Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome
      activation, both of which require the bacterial type VI secretion system (T6SS).
      Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B.
      cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to
      sense pathogen modification and inactivation of Rho GTPases, representing a new
      paradigm in mammalian innate immunity. 

PMID- 24919151
TI  - Quantum computing: powered by magic.

PMID- 24919152
TI  - Contextuality supplies the 'magic' for quantum computation.
AB  - Quantum computers promise dramatic advantages over their classical counterparts,
      but the source of the power in quantum computing has remained elusive. Here we
      prove a remarkable equivalence between the onset of contextuality and the
      possibility of universal quantum computation via 'magic state' distillation,
      which is the leading model for experimentally realizing a fault-tolerant quantum
      computer. This is a conceptually satisfying link, because contextuality, which
      precludes a simple 'hidden variable' model of quantum mechanics, provides one of
      the fundamental characterizations of uniquely quantum phenomena. Furthermore,
      this connection suggests a unifying paradigm for the resources of quantum
      information: the non-locality of quantum theory is a particular kind of
      contextuality, and non-locality is already known to be a critical resource for
      achieving advantages with quantum communication. In addition to clarifying these
      fundamental issues, this work advances the resource framework for quantum
      computation, which has a number of practical applications, such as characterizing
      the efficiency and trade-offs between distinct theoretical and experimental
      schemes for achieving robust quantum computation, and putting bounds on the
      overhead cost for the classical simulation of quantum algorithms. 

PMID- 24919153
TI  - Single-cell RNA-seq reveals dynamic paracrine control of cellular variation.
AB  - High-throughput single-cell transcriptomics offers an unbiased approach for
      understanding the extent, basis and function of gene expression variation between
      seemingly identical cells. Here we sequence single-cell RNA-seq libraries
      prepared from over 1,700 primary mouse bone-marrow-derived dendritic cells
      spanning several experimental conditions. We find substantial variation between
      identically stimulated dendritic cells, in both the fraction of cells detectably
      expressing a given messenger RNA and the transcript's level within expressing
      cells. Distinct gene modules are characterized by different temporal
      heterogeneity profiles. In particular, a 'core' module of antiviral genes is
      expressed very early by a few 'precocious' cells in response to uniform
      stimulation with a pathogenic component, but is later activated in all cells. By
      stimulating cells individually in sealed microfluidic chambers, analysing
      dendritic cells from knockout mice, and modulating secretion and extracellular
      signalling, we show that this response is coordinated by interferon-mediated
      paracrine signalling from these precocious cells. Notably, preventing cell-to
      cell communication also substantially reduces variability between cells in the
      expression of an early-induced 'peaked' inflammatory module, suggesting that
      paracrine signalling additionally represses part of the inflammatory program. Our
      study highlights the importance of cell-to-cell communication in controlling
      cellular heterogeneity and reveals general strategies that multicellular
      populations can use to establish complex dynamic responses. 

PMID- 24919154
TI  - Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune
      tolerance to cancer.
AB  - Inhibitors against the p110delta isoform of phosphoinositide-3-OH kinase (PI(3)K)
      have shown remarkable therapeutic efficacy in some human leukaemias. As p110delta
      is primarily expressed in leukocytes, drugs against p110delta have not been
      considered for the treatment of solid tumours. Here we report that p110delta
      inactivation in mice protects against a broad range of cancers, including non
      haematological solid tumours. We demonstrate that p110delta inactivation in
      regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour
      regression. Thus, p110delta inhibitors can break tumour-induced immune tolerance
      and should be considered for wider use in oncology.

PMID- 24919157
TI  - Test Statistics and Confidence Intervals to Establish Noninferiority between
      Treatments with Ordinal Categorical Data.
AB  - The problem for establishing noninferiority is discussed between a new treatment
      and a standard (control) treatment with ordinal categorical data. A measure of
      treatment effect is used and a method of specifying noninferiority margin for the
      measure is provided. Two Z-type test statistics are proposed where the estimation
      of variance is constructed under the shifted null hypothesis using U-statistics.
      Furthermore, the confidence interval and the sample size formula are given based
      on the proposed test statistics. The proposed procedure is applied to a dataset
      from a clinical trial. A simulation study is conducted to compare the performance
      of the proposed test statistics with that of the existing ones, and the results
      show that the proposed test statistics are better in terms of the deviation from
      nominal level and the power. 

PMID- 24919156
TI  - Dynamic pathways of -1 translational frameshifting.
AB  - Spontaneous changes in the reading frame of translation are rare (frequency of
      10(-3) to 10(-4) per codon), but can be induced by specific features in the
      messenger RNA (mRNA). In the presence of mRNA secondary structures, a
      heptanucleotide 'slippery sequence' usually defined by the motif X XXY YYZ, and
      (in some prokaryotic cases) mRNA sequences that base pair with the 3' end of the
      16S ribosomal rRNA (internal Shine-Dalgarno sequences), there is an increased
      probability that a specific programmed change of frame occurs, wherein the
      ribosome shifts one nucleotide backwards into an overlapping reading frame (-1
      frame) and continues by translating a new sequence of amino acids. Despite
      extensive biochemical and genetic studies, there is no clear mechanistic
      description for frameshifting. Here we apply single-molecule fluorescence to
      track the compositional and conformational dynamics of individual ribosomes at
      each codon during translation of a frameshift-inducing mRNA from the dnaX gene in
      Escherichia coli. Ribosomes that frameshift into the -1 frame are characterized
      by a tenfold longer pause in elongation compared to non-frameshifted ribosomes,
      which translate through unperturbed. During the pause, interactions of the
      ribosome with the mRNA stimulatory elements uncouple EF-G catalysed translocation
      from normal ribosomal subunit reverse-rotation, leaving the ribosome in a non
      canonical intersubunit rotated state with an exposed codon in the aminoacyl-tRNA
      site (A site). tRNA(Lys) sampling and accommodation to the empty A site and EF-G
      action either leads to the slippage of the tRNAs into the -1 frame or maintains
      the ribosome into the 0 frame. Our results provide a general mechanistic and
      conformational framework for -1 frameshifting, highlighting multiple kinetic
      branchpoints during elongation. 

PMID- 24919158
TI  - Automatic segmentation of breast MR images through a Markov random field
      statistical model.
AB  - An algorithm dedicated to automatic segmentation of breast magnetic resonance
      images is presented in this paper. Our approach is based on a pipeline that
      includes a denoising step and statistical segmentation. The noise removal
      preprocessing relies on an anisotropic diffusion scheme, whereas the statistical
      segmentation is conducted through a Markov random field model. The continuous
      updating of all parameters governing the diffusion process enables automatic
      denoising, and the partial volume effect is also addressed during the labeling
      step. To assess the relevance, the Jaccard similarity coefficient was computed.
      Experiments were conducted on synthetic data and breast magnetic resonance images
      extracted from a high-risk population. The relevance of the approach for the
      dataset is highlighted, and we demonstrate accuracy superior to that of
      traditional clustering algorithms. The results emphasize the benefits of both
      denoising guided by input data and the inclusion of spatial dependency through a
      Markov random field. For example, the Jaccard coefficient for the clinical data
      was increased by 114%, 109%, and 140% with respect to a K-means algorithm and,
      respectively, for the adipose, glandular and muscle and skin components.
      Moreover, the agreement between the manual segmentations provided by an
      experienced radiologist and the automatic segmentations performed with this
      algorithm was good, with Jaccard coefficients equal to 0.769, 0.756, and 0.694
      for the above-mentioned classes. 

PMID- 24919155
TI  - Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53.
AB  - Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR),
      but the molecular mechanisms by which UVR drives melanomagenesis remain unclear.
      The most common somatic mutation in melanoma is a V600E substitution in BRAF,
      which is an early event. To investigate how UVR accelerates oncogenic BRAF-driven
      melanomagenesis, we used a BRAF(V600E) mouse model. In mice expressing
      BRAF(V600E) in their melanocytes, a single dose of UVR that mimicked mild sunburn
      in humans induced clonal expansion of the melanocytes, and repeated doses of UVR
      increased melanoma burden. Here we show that sunscreen (UVA superior, UVB sun
      protection factor (SPF) 50) delayed the onset of UVR-driven melanoma, but only
      provided partial protection. The UVR-exposed tumours showed increased numbers of
      single nucleotide variants and we observed mutations (H39Y, S124F, R245C, R270C,
      C272G) in the Trp53 tumour suppressor in approximately 40% of cases. TP53 is an
      accepted UVR target in human non-melanoma skin cancer, but is not thought to have
      a major role in melanoma. However, we show that, in mice, mutant Trp53
      accelerated BRAF(V600E)-driven melanomagenesis, and that TP53 mutations are
      linked to evidence of UVR-induced DNA damage in human melanoma. Thus, we provide
      mechanistic insight into epidemiological data linking UVR to acquired naevi in
      humans. Furthermore, we identify TP53/Trp53 as a UVR-target gene that cooperates
      with BRAF(V600E) to induce melanoma, providing molecular insight into how UVR
      accelerates melanomagenesis. Our study validates public health campaigns that
      promote sunscreen protection for individuals at risk of melanoma. 

PMID- 24919159
TI  - Serious adverse events associated with vasopressin and norepinephrine infusion in
      septic shock.
AB  - OBJECTIVE: The frequency, risk factors, and mortality rates of serious adverse
      events associated with the use of vasopressin and norepinephrine are not clear.
      The objectives of this study were to determine frequency, risk factors (including
      candidate gene polymorphisms), and outcomes of serious adverse events in septic
      shock patients. DESIGN: Retrospective cohort study using multicenter discovery
      and single-center validation cohorts. SETTING: ICUs at academic teaching centers.
      PATIENTS: Five hundred ninety-seven patients with septic shock in discovery
      (Vasopressin and Septic Shock trial) and 533 patients in validation (St. Paul's
      Hospital) cohorts. INTERVENTION: Vasopressin and norepinephrine for septic shock.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was 90-day mortality
      rates of patients with and without serious adverse events. Secondary outcome
      variables were the association between vasopressor genotype pathway
      polymorphisms, plasma vasopressin levels, and serious adverse events. Plasma
      vasopressin concentrations were measured at baseline, 6 hours, 24 hours, 72
      hours, and 7 days after vasopressor infusion. Patients with septic shock were
      genotyped for 268 vasopressor pathway tag single-nucleotide polymorphisms.
      Serious adverse events occurred in 10.5% and 9.7% of patients in Vasopressin and
      Septic Shock trial and St. Paul's Hospital cohorts, respectively. Patients who
      had serious adverse events had higher mortality (p < 0.01) than patients without
      serious adverse events (adjusted for age, serum lactate, Acute Physiology and
      Chronic Health Evaluation II, and maximum dose of norepinephrine day 1) (hazard
      ratio, 2.97; 95% CI, 2.20-4.00; p < 0.001 and hazard ratio, 1.89; 95% CI, 1.26
      2.85; p = 0.002 in Vasopressin and Septic Shock trial and St. Paul's Hospital,
      respectively). There was no difference in the area under the plasma vasopressin
      concentration curve between patients with and without serious adverse events (p =
      0.1). The AA genotype of rs28418396 single-nucleotide polymorphism (near the
      arginine vasopressin receptor 1b gene) was significantly associated with serious
      adverse events in discovery and validation cohorts (p = 0.001 and p = 0.04,
      respectively). CONCLUSION: Serious adverse events associated with vasopressin and
      norepinephrine in patients who have septic shock are associated with increased
      mortality and morbidity. AA genotype of rs28418396 single-nucleotide polymorphism
      near the arginine vasopressin receptor 1b gene is associated with serious adverse
      events. The mechanism of this association requires investigation.

PMID- 24919160
TI  - Sepsis severity score: an internationally derived scoring system from the
      surviving sepsis campaign database*.
AB  - OBJECTIVE: As the Surviving Sepsis Campaign was assessing patient-level data over
      multiple countries, we sought to evaluate the use of a pragmatic and parsimonious
      severity-of-illness scoring system for patients with sepsis in an attempt to
      provide appropriate comparisons with practical application. DESIGN: Prospective,
      observational evaluation. PATIENTS: Data from 23,438 patients with suspected or
      confirmed sepsis from 218 hospitals in 18 countries were evaluated. SETTING: This
      analysis was conducted on prospective data submitted to a database from January
      2005 through March 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Maximum likelihood logistic regression was used to estimate model coefficients,
      and these were then used to develop a Sepsis Severity Score. The probability of
      hospital mortality was estimated using the Sepsis Severity Score as the sole
      variable in a logistic regression model. Univariable logistic regression
      determined which variables were included in the multivariable predictor model.
      The scale of continuous variables was assessed using fractional polynomials. Two
      way interactions between variables were considered for model inclusion if the
      interaction p value is less than 0.05. The prediction model was developed based
      on randomly selecting 90% of available patients and was validated on the
      remaining 10%, as well as by using a bootstrapping technique. The p values for
      the Hosmer-Lemeshow goodnessof-fit statistic in the developmental and validation
      datasets were considerably greater than 0.05, suggesting good calibration.
      Development and validation areas under the receiver operator curve curves were
      0.736 and 0.748, respectively. Observed and estimated probabilities of hospital
      mortality for the total population were both 0.334. The validation and the
      developmental datasets were gradually compared over deciles of predicted
      mortality and found to be very similar. CONCLUSION: The Sepsis Severity Score
      accurately estimated the probability of hospital mortality in severe sepsis and
      septic shock patients. It performed well with respect to calibration and
      discrimination, which remained consistent over deciles. It functioned well over
      international geographic regions. This robust, population-specific evaluation of
      international severe sepsis patients provides an effective and accurate mortality
      estimate allowing for appropriate quality comparisons with practical clinical and
      research application.

PMID- 24919161
TI  - Assessing work ability--a cross-sectional study of interrater agreement between
      disability claimants, treating physicians, and medical experts.
AB  - OBJECTIVES: It is unclear to what extent assessments of work ability differ
      between disability claimants, their treating physicians, and multidisciplinary
      medical expert teams. METHODS: We compared assessments of work ability for
      consecutive disability claimants referred to a multidisciplinary assessment
      center in Switzerland over a 4-year period. Assessments were made for the last
      job (LJ) prior to claiming a disability benefit and an alternative job (AJ)
      thought to suit the claimant's physical and mental abilities. Mean differences
      (MD) in percentage work ability between assessments from claimants, physicians,
      and experts were then estimated in a linear regression model. RESULTS: The 3562
      claims made during the study period were mostly due to musculoskeletal and
      depressive disorders. Assessments differed little between claimants and
      physicians [LJ MD 1.3% (95% confidence interval [95% CI] 0.5-2.2%); AJ MD 11%
      (95% CI 10-12%)]. Experts on average assessed a claimant's work ability higher
      than either the claimant or physician, particularly in the AJ [MD between expert
      and claimant 57% (95% CI 56-58%) and between expert and physician 46% (95% CI 45
      48%)]. CONCLUSIONS: Assessments of work ability differed substantially between
      experts in multidisciplinary medical teams and both claimants and their treating
      physicians. A careful evaluation of the disability assessment process is needed
      in an effort to reduce disagreement between expert teams and treating physicians
      and so improve acceptance of the process.

PMID- 24919162
TI  - Tunable chiral spin texture in magnetic domain-walls.
AB  - Magnetic domain-walls (DWs) with a preferred chirality exhibit very efficient
      current-driven motion. Since structural inversion asymmetry (SIA) is required for
      their stability, the observation of chiral domain walls in highly symmetric
      Pt/Co/Pt is intriguing. Here, we tune the layer asymmetry in this system and
      observe, by current-assisted DW depinning experiments, a small chiral field which
      sensitively changes. Moreover, we convincingly link the observed efficiency of DW
      motion to the DW texture, using DW resistance as a direct probe for the internal
      orientation of the DW under the influence of in-plane fields. The very delicate
      effect of capping layer thickness on the chiral field allows for its accurate
      control, which is important in designing novel materials for optimal spin-orbit
      torque-driven DW motion. 

PMID- 24919163
TI  - Short- and mid-term outcomes after early surgical training in laparoscopic
      colorectal cancer surgery: trainees' performance has no negative impact.
AB  - BACKGROUND: This study aimed to evaluate the safety and quality of laparoscopic
      colorectal cancer surgery undertaken by trainees. PATIENTS AND METHODS: From a
      prospectively maintained database, we identified 456 consecutive patients who
      underwent laparoscopic resection for colorectal cancer between 2006 and 2010.
      Short-term operative outcomes, relapse-free survival (RFS), and overall survival
      (OS) were compared between operations undertaken by the experts (E group) and
      trainees (T group). Multivariate analyses were performed for RFS and OS in stage
      II/III disease. RESULTS: Trainees performed 313 surgeries (68.6%) and completed
      the procedure by themselves in 297 cases (94.9%). Short-term outcomes, including
      operative time, blood loss, conversion, complication, mortality, and retrieval of
      less than 12 lymph nodes, were comparable between the E group and the T group.
      After a median follow-up period of 35 months, RFS and OS were similar between the
      two groups, with the exception of OS for stage II (3-year OS for E group versus T
      group, 96.9% versus 87.0%; P=.029); however, this difference disappeared after
      multivariate analyses. Multivariate analyses showed that positive resection
      margin and higher log carcinoembryonic antigen (CEA) levels were associated with
      lower RFS. Furthermore, increasing age, positive resection margin, higher log CEA
      levels, intraoperative surgeon exchange, rectal cancer, postoperative
      complications, absence of postoperative chemotherapy, and shorter operative time
      were associated with poor OS. CONCLUSIONS: Laparoscopic operations undertaken by
      trainees did not negatively affect short-term outcomes and were not associated
      with impaired mid-term oncologic outcomes. Our findings support early initiation
      of training in laparoscopic surgery for colorectal cancer treatment.

PMID- 24919164
TI  - Schizophrenia: from genetics to biology to predictive medicine.
AB  - Identifying genes for psychiatric disorders using traditional genetic approaches
      has thus far proven quite difficult. Reasons for this include the complexity of
      these disorders and the poor definition of the clinical phenotype. However,
      recent studies have demonstrated the power of an approach called convergent
      functional genomics (CFG). CFG is a methodology that integrates different types
      of data to increase the ability to identify genes involved in various psychiatric
      and nonpsychiatric disorders. The work exemplified in this article integrated
      human brain and blood gene expression data, relevant animal model brain and blood
      gene expression data, and human genetic data to identify candidate genes and
      blood biomarkers for schizophrenia. 

PMID- 24919165
TI  - The longitudinal course of cognitive impairment in schizophrenia: an examination
      of data from premorbid through posttreatment phases of illness.
AB  - Cognitive impairment is a core feature of schizophrenia that is present across
      the course of the illness. However, due to complexities of studying cognitive
      decline in patients prior to the onset of illness, the longitudinal course is not
      fully understood. The cognitive effects in patients with schizophrenia are
      robust, with a 1.5 to 2.5 standard deviation gap between patients and healthy
      controls on composite scores. People with schizophrenia manifest a prior history
      of cognitive impairment in the premorbid phases of the illness. Examination of
      school records suggests that children who will eventually develop schizophrenia
      begin school at a level of functioning that is a full grade behind their peers,
      with the gap increasing by the time they finish high school. Epidemiologic work
      suggests that there are both static cognitive impairments and developmental lags
      in these patients during childhood, well before the illness is fully manifest.
      Although there was initial promise of improved cognitive function with second
      generation antipsychotic treatment, more recent studies have suggested no
      differences among antipsychotics, with the initial appearance of improvement very
      likely attributable to practice effects, inappropriate medication dosing, and
      poor study design. Two large, prominent studies evaluating first- and second
      generation antipsychotics suggested that, although there was slight to modest
      improvement in cognitive function for all treatments, there were no differences
      among medications, regardless of the generation of the agents. In summary,
      patients who develop schizophrenia, on average, demonstrate cognitive impairment
      beginning as early as the first grade, with deterioration seen across school
      years. Further, these patients had substantial cognitive deficits after the
      initiation of psychosis. Finally, while antipsychotic treatment improves
      symptoms, antipsychotics have little impact on cognition, and there appear to be
      no differences in the degree of cognitive improvement between first- and second
      generation agents. 

PMID- 24919166
TI  - Social cognition in schizophrenia.
AB  - The topic of social cognition has attracted considerable interest in
      schizophrenia over the last several years. This construct generally refers to the
      detection, processing, and utilization of social information and, within the
      field of schizophrenia, includes several skills such as recognizing emotion,
      understanding the thoughts and intentions of others, and interpreting social
      cues. Individuals with schizophrenia show significant impairments in social
      cognition, and these impairments are strongly related to functional outcome.
      Treating social cognition yields significant improvements in real-world outcomes,
      including social functioning and social skill. Importantly, social cognitive
      abilities are linked to specific neural circuits that have been shown to be
      abnormal in individuals with schizophrenia. Investigations of these neural
      networks in patients have also demonstrated that brain activation is
      significantly correlated with social functioning, which suggests that abnormal
      activation in social cognitive networks may serve as a mechanism for social
      dysfunction in schizophrenia. Among the many challenges in this area is the issue
      of measurement. There is disagreement about which tasks best measure social
      cognition and many existing measures show poor psychometric properties. A recent
      project, called the Social Cognition Psychometric Evaluation (SCOPE) study, aims
      to address these problems by providing the field with a well-validated battery of
      social cognitive tasks that can be used in treatment outcome trials. Research is
      honing in on the potential mechanisms of social cognitive impairment in patients,
      and with improved measurement, there is promise for optimizing behavioral and
      pharmacologic interventions and remediation strategies. 

PMID- 24919167
TI  - Why are the outcomes in patients with schizophrenia so poor?
AB  - Despite many advances in the treatment of schizophrenia over the past 50 years,
      the outcomes for many patients with schizophrenia remain poor. While the majority
      of patients with a first episode of schizophrenia may be able to achieve and
      maintain a remission of symptoms, only 1 in 7 patients are likely to meet
      criteria for recovery. These findings could be easily reconciled if schizophrenia
      could be established to be a progressive brain disease. Results from longitudinal
      studies of brain structure, cognitive functioning, and clinical outcomes,
      however, do not support this view. The poor outcomes so commonly observed are
      likely best explained by poor access to treatment, poor engagement in ongoing
      care, poor treatment response, and poor adherence together with the cumulative
      negative impact of substance abuse, comorbid psychiatric disorders, cognitive
      deficits, and multiple social determinants of health. 

PMID- 24919168
TI  - The early longitudinal course of cognitive deficits in schizophrenia.
AB  - Cognitive impairment is a core feature of schizophrenia. However, the
      longitudinal course and pattern of this impairment, and its relationship to
      functional outcome, are not fully understood. Among the likely factors in the
      persistence of cognitive deficits in schizophrenia are brain tissue changes over
      time, which in turn appear to be related to antipsychotic medication adherence.
      Cognitive deficits are viewed as a core feature of schizophrenia primarily
      because cognitive deficits clearly exist before the onset of psychosis and can
      predict illness onset among those at high risk of developing the illness.
      Additionally, these deficits often persist during symptomatic remissions in
      patients and are relatively stable across time both in patients and in
      individuals at risk for schizophrenia. Despite clear evidence that cognitive
      impairment can predict functional outcome in chronic schizophrenia, results of
      studies examining this relationship in the early phase of psychosis have been
      mixed. Recent data, however, strongly suggest that interventions targeting early
      cognitive deficits may be crucial to the prevention of chronic disability and
      thus should be a prominent target for therapy. Finally, it is vital to keep
      schizophrenia patients consistently on their antipsychotic medications. A novel
      method of examining intracortical myelin volume indicated that the choice of
      antipsychotic treatment had a differential impact on frontal myelination. These
      data suggest that long-acting injectable antipsychotic medication may prevent
      patients from declining further through a combination of better adherence and
      pharmacokinetics. 

PMID- 24919169
TI  - Patient outcomes within schizophrenia treatment: a look at the role of long
      acting injectable antipsychotics.
AB  - Compliance is a critical issue across all chronic conditions, including
      schizophrenia. Compliance is not an all-or-nothing phenomenon, with a continuum
      from taking all medications as prescribed to partial compliance to complete
      noncompliance. Partial compliance is a serious problem that may result in abrupt
      dose changes leading to unanticipated adverse effects and can demoralize the
      patient. Further, there is a nearly 5-fold increase in the risk of relapse in
      first-episode patients when antipsychotic drug treatment is discontinued. Taken
      together, these data indicate that it is critical to ensure continuous delivery
      of antipsychotic treatment. Atypical antipsychotic medications were expected to
      result in better adherence, primarily because of the anticipated improved
      efficacy and safety profile. However, atypical agents have poor adherence,
      irrespective of the type of atypical medication, making it difficult to predict
      which patients are taking their oral medications. Long-acting injectable (LAI)
      agents may minimize the fluctuations in peak and overall plasma levels compared
      with oral agents, indicating they may allow more consistent and predictable
      administration. Based on clinical experience in my practice, several important
      observations regarding LAI use in patients with schizophrenia have been
      identified. First, there are potential advantages to using LAIs, including
      assistance in understanding reasons for poor response, the possibility of
      eliminating daily pill ingestion, and the elimination of the abrupt loss of
      medication coverage. There are also several potential obstacles to the use of
      LAIs, including a lack of infrastructure for the delivery and disposal of
      syringes and the ease of use with the oral agents. Several strategies can be used
      to increase patient willingness to initiate and continue LAI therapy. Strategies
      to improve acceptance involve presenting the option with enthusiasm, ensuring
      proper goal setting, educating the patient that this treatment is not equivalent
      to emergency injections, and repeatedly recommending LAI therapy. Adherence can
      be improved by ensuring samples are available in the clinical setting at all
      times. 

PMID- 24919170
TI  - What is the evidence for changes in cognition and functioning over the lifespan
      in patients with schizophrenia?
AB  - Cognitive deficits in schizophrenia are important predictors of impairment in
      most functional domains and are a critical therapeutic target. These deficits
      appear at or before the onset of illness, are stable across time in most
      patients, and can be improved by cognitive remediation treatments. Recent
      evidence, however, suggests that cognitive function does not necessarily follow a
      pattern of age-related decline. Several studies evaluated this pattern of decline
      in schizophrenia patients compared to both natural aging and degenerative
      conditions such as Alzheimer's disease. Age-related differences were not
      comparable to either normal aging or Alzheimer's disease. Older patients with an
      extensive history of illness and protracted institutionalization have shown a
      greater progressive decline. These deficits were also observed in older patients
      who were no longer institutionalized, with these patients demonstrating decline
      in functional capacity across time compared to healthy controls and patients with
      no lengthy institutional stay. There were 2 clear conclusions from this body of
      data. First, there appear to be 2 separate periods of deterioration in
      schizophrenia patients. These patients appear to decline the most at 2 key time
      points; the first occurs some time prior to the first psychotic episode and the
      second begins at approximately 65 years of age. The second important conclusion
      is that these 2 important periods of time may be the time point at which an
      aggressive intervention may have the greatest impact. 

PMID- 24919171
TI  - Expression, production, and renaturation of a functional single-chain variable
      antibody fragment (scFv) against human ICAM-1.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is an important factor in the
      progression of inflammatory responses in vivo. To develop a new anti-inflammatory
      drug to block the biological activity of ICAM-1, we produced a monoclonal
      antibody (Ka=4.19 * 10(-8) M) against human ICAM-1. The anti-ICAM-1 single-chain
      variable antibody fragment (scFv) was expressed at a high level as inclusion
      bodies in Escherichia coli. We refolded the scFv (Ka=2.35 * 10(-7) M) by ion
      exchange chromatography, dialysis, and dilution. The results showed that column
      chromatography refolding by high-performance Q Sepharose had remarkable
      advantages over conventional dilution and dialysis methods. Furthermore, the anti
      ICAM-1 scFv yield of about 60 mg/L was higher with this method. The purity of the
      final product was greater than 90%, as shown by denaturing gel electrophoresis.
      Enzyme-linked immunosorbent assay, cell culture, and animal experiments were used
      to assess the immunological properties and biological activities of the renatured
      scFv.

PMID- 24919172
TI  - Modeling pulmonary fibrosis by abnormal expression of
      telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia.
AB  - Limitations on tissue proliferation capacity determined by telomerase/apoptosis
      balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In
      addition, collagen V shows promise as an inductor of apoptosis. We evaluated the
      quantitative relationship between the telomerase/apoptosis index, collagen V
      synthesis, and epithelial/fibroblast replication in mice exposed to butylated
      hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were
      analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase
      expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were
      evaluated by immunohistochemistry, in situ detection of apoptosis, electron
      microscopy, immunofluorescence, and histomorphometry. Electron microscopy
      confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in
      apoptosis. Immunostaining showed increased nuclear expression of telomerase in
      AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial
      pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green
      birefringence of type I and III collagens in the alveolar wall and type V
      collagen in the basement membrane of alveolar capillaries. The increase in
      collagen V was greater than collagens I and III in scarring areas of UIP. A
      significant direct association was found between collagen V and AEC2 apoptosis.
      We concluded that telomerase, collagen V fiber density, and apoptosis evaluation
      in experimental UIP offers the potential to control reepithelization of alveolar
      septa and fibroblast proliferation. Strategies aimed at preventing high rates of
      collagen V synthesis, or local responses to high rates of cell apoptosis, may
      have a significant impact in pulmonary fibrosis.

PMID- 24919173
TI  - Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease
      patients is predominantly multifocal and associated with kidney and liver volume.
AB  - Positron-emission tomography/computed tomography (PET/CT) has improved cyst
      infection (CI) management in autosomal dominant polycystic kidney disease
      (ADPKD). The determinants of kidney and/or liver involvement, however, remain
      uncertain. In this study, we evaluated clinical and imaging factors associated
      with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study
      was performed in hospital-admitted ADPKD patients with suspected CI. Clinical,
      imaging and surgical data were analyzed. Features of infected cysts were
      evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by
      CT-derived multiplanar reconstruction. CI was detected in 18 patients who
      experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and
      concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and
      PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture
      (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss
      (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with
      LCI. PET/CT revealed that three or more infected cysts were present in 70% of the
      episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91,
      P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV
      was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut
      off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for
      invasive procedures was observed in LCI (P<0.01), and the overall mortality was
      20.8%. This study supports PET/CT as the most sensitive imaging method for
      diagnosis of cyst infection, confirms the multifocal nature of most hospital
      admitted episodes, and reveals an association of kidney and liver volumes with
      this complication.

PMID- 24919174
TI  - Mortality rate after open Roux-in-Y gastric bypass: a 10-year follow-up.
AB  - The prevalence of obesity has increased to epidemic status worldwide. Thousands
      of morbidly obese individuals undergo bariatric surgery for sustained weight
      loss; however, mid- and long-term outcomes of this surgery are still uncertain.
      Our objective was to estimate the 10-year mortality rate, and determine risk
      factors associated with death in young morbidly obese adults who underwent
      bariatric surgery. All patients who underwent open Roux-in-Y gastric bypass
      surgery between 2001 and 2010, covered by an insurance company, were analyzed to
      determine possible associations between risk factors present at the time of
      surgery and deaths related and unrelated to the surgery. Among the 4344 patients
      included in the study, 79% were female with a median age of 34.9 years and median
      body mass index (BMI) of 42 kg/m(2). The 30-day and 10-year mortality rates were
      0.55 and 3.34%, respectively, and 53.7% of deaths were related to early or late
      complications following bariatric surgery. Among these, 42.7% of the deaths were
      due to sepsis and 24.3% to cardiovascular complications. Male gender, age >=50
      years, BMI >=50 kg/m(2), and hypertension significantly increased the hazard for
      all deaths (P<0.001). Age >=50 years, BMI >=50 kg/m(2), and surgeon inexperience
      elevated the hazard of death from causes related to surgery. Male gender and age
      >=50 years were the factors associated with increased mortality from death not
      related to surgery. The overall risk of death after bariatric surgery was quite
      low, and half of the deaths were related to the surgery. Older patients and
      superobese patients were at greater risk of surgery-related deaths, as were
      patients operated on by less experienced surgeons.

PMID- 24919175
TI  - Meta-analysis on the efficacy and tolerability of the augmentation of
      antidepressants with atypical antipsychotics in patients with major depressive
      disorder.
AB  - We assessed the efficacy and tolerability of the augmentation of antidepressants
      (ATDs) with atypical antipsychotics (AAPs) to treat patients with major
      depressive disorder. A retrograde study to identify relevant patient data
      included databases of PubMed, EMBASE, Cochrane Central Register of Controlled
      Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials,
      involving 3807 participants, were identified. The remission rate (RR) and overall
      response rate (ORR) of adjunctive treatment with AAPs were significantly higher
      than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68
      (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks)
      treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly
      different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94,
      z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups
      with or without sedative drugs. The discontinuation rate due to adverse effects
      was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78,
      P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs
      (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a
      placebo in improving response and remission rates, although associated with a
      higher discontinuation rate due to adverse effects.

PMID- 24919176
TI  - The psychosexual profile of sexual assistants: an internet-based explorative
      study.
AB  - INTRODUCTION: Sexual assistance may have some aspects that resemble prostitution
      and others that might lead one to think of sexual assistants as similar to a
      group of subjects whose sexual object is disability (devotees). In this study, we
      investigate whether a rigorous selection and training process on the part of
      specialised organisations may reduce the risk of training subjects with an
      atypical sexual interest and behaviours resembling prostitution. MATERIALS AND
      METHODS: The study population consisted of 152 subjects defining themselves as
      sexual assistants. Subjects were initially contacted on websites specifically
      dedicated to sexual assistants and prostitutes. One hundred and twenty subjects
      were selected, by propensity score analysis, and studied by means of a modified
      version of a semi-structured questionnaire previously developed to investigate a
      population of subjects attracted by disability. RESULTS: The study group was
      composed of 80 trained and 40 untrained sexual assistants, with mean ages of 41.5
      (SD +/-12.58) and 44.5 (SD +/-11.62), respectively. A significant number of
      untrained subjects affirmed that their motivation in carrying out sexual
      assistance was of a remunerative nature, while this number was lower among the
      trained assistants (p = 0.001). Nearly all untrained subjects claimed to do one
      or more of the following activities during sexual assistance: sexual intercourse,
      oral sex, and masturbation. Among the trained subjects, however, only 47.5%
      claimed to do one or more of these activities, which means that there is a
      significant gap between trained and untrained assistants (p<0.0001). The
      existence of an atypical sexual interest was more evident between untrained
      rather than between trained subjects (p<0.0001). CONCLUSIONS: Sexual assistance
      represents a way through which people affected by disabilities may attain the
      right to explore their sexuality in a safe setting. This can be guaranteed only
      if sexual assistants are trained and carefully selected by specialised
      organisations.

PMID- 24919178
TI  - Long-lasting, kin-directed female interactions in a spatially structured wild
      boar social network.
AB  - Individuals can increase inclusive fitness benefits through a complex network of
      social interactions directed towards kin. Preferential relationships with
      relatives lead to the emergence of kin structures in the social system. Cohesive
      social groups of related individuals and female philopatry of wild boar create
      conditions for cooperation through kin selection and make the species a good
      biological model for studying kin structures. Yet, the role of kinship in shaping
      the social structure of wild boar populations is still poorly understood. In the
      present study, we investigated spatio-temporal patterns of associations and the
      social network structure of the wild boar Sus scrofa population in Bialowieza
      National Park, Poland, which offered a unique opportunity to understand wild boar
      social interactions away from anthropogenic factors. We used a combination of
      telemetry data and genetic information to examine the impact of kinship on
      network cohesion and the strength of social bonds. Relatedness and spatial
      proximity between individuals were positively related to the strength of social
      bond. Consequently, the social network was spatially and genetically structured
      with well-defined and cohesive social units. However, spatial proximity between
      individuals could not entirely explain the association patterns and network
      structure. Genuine, kin-targeted, and temporarily stable relationships of females
      extended beyond spatial proximity between individuals while males interactions
      were short-lived and not shaped by relatedness. The findings of this study
      confirm the matrilineal nature of wild boar social structure and show how social
      preferences of individuals translate into an emergent socio-genetic population
      structure. 

PMID- 24919177
TI  - Reactivation of multiple viruses in patients with sepsis.
AB  - A current controversy is whether patients with sepsis progress to an
      immunosuppressed state. We hypothesized that reactivation of latent viruses
      occurred with prolonged sepsis thereby providing evidence of clinically-relevant
      immunosuppression and potentially providing a means to serially-monitor patients'
      immune status. Secondly, if viral loads are markedly elevated, they may
      contribute to morbidity and mortality. This study determined if reactivation of
      herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and
      correlated with severity. Serial whole blood and plasma samples from 560
      critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched
      patients were analyzed by quantitative-polymerase-chain-reaction for
      cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes
      virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine.
      Detectable virus was analyzed with respect to secondary fungal and opportunistic
      bacterial infections, ICU duration, severity of illness, and survival. Patients
      with protracted sepsis had markedly increased frequency of detectable virus.
      Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV
      (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of
      two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after
      sepsis onset. A small subgroup of septic patients had markedly elevated viral
      loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV,
      DNAemia was uncommon in critically-ill non-septic patients and in age-matched
      healthy controls. Compared to septic patients without DNAemia, septic patients
      with viremia had increased fungal and opportunistic bacterial infections.
      Patients with detectable CMV in plasma had higher 90-day mortality compared to
      CMV-negative patients; p<0.05. Reactivation of latent viruses is common with
      prolonged sepsis, with frequencies similar to those occurring in transplant
      patients on immunosuppressive therapy and consistent with development of an
      immunosuppressive state. Whether reactivated latent viruses contribute to
      morbidity and mortality in sepsis remains unknown. 

PMID- 24919179
TI  - The interplay between histone deacetylases and c-Myc in the transcriptional
      suppression of HPP1 in colon cancer.
AB  - HPP1 (hyperplastic polyposis protein 1), a tumor suppressor gene, is
      downregulated by promoter hypermethylation in a number of tumor types including
      colon cancer. c-Myc is also known to play a role in the suppression of HPP1
      expression via binding to a promoter region cognate E-box site. The contribution
      of histone deacetylation as an additional epigenetic mechanism and its potential
      interplay with c-Myc in the transcriptional regulation of HPP1 are unknown. We
      have shown that the treatment of the HPP1-non-expressing colon cancer cell lines,
      HCT116 and DLD-1 with HDAC inhibitors results in re-expression of HPP1. RNAi
      mediated knockdown of c-Myc as well as of HDAC2 and HDAC3 in HCT116 and of HDAC1
      and HDAC3 in DLD-1 also resulted in significant re-expression of HPP1. Co
      immunoprecipitation (IP), chromatin IP (ChIP), and sequential ChIP experiments
      demonstrated binding of c-Myc to the HPP1 promoter with recruitment of and direct
      interaction with HDAC3. In summary, we have demonstrated that c-Myc contributes
      to the epigenetic regulation of HPP1 via the dominant recruitment of HDAC3. Our
      findings may lead to a greater biologic understanding for the application of
      targeted use of HDAC inhibitors for anti-cancer therapy. 

PMID- 24919180
TI  - Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31-
      cells attenuates post-MI LV remodeling more than does cell transplantation alone:
      neither intervention enhances functionally significant cardiomyocyte
      regeneration.
AB  - Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two
      potent cell survival and regenerative factors in response to myocardial injury
      (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca
      1+/CD31- cells would improve the outcome of transplantation therapy in response
      to the altered hostile microenvironment post MI. One million adenovirus nuclear
      LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after
      left anterior descending coronary artery (LAD) ligation in mice. Recombinant
      mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left
      ventricular (LV) function was assessed by echocardiography 4 weeks after the
      transplantation. The cell engraftment, differentiation and cardiomyocyte
      regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed
      viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI,
      17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01). IGF+HGF significantly enhanced the
      benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9,
      P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF
      supplementation increased the cell engraftment rate, promoted the transplanted
      cell survival, enhanced angiogenesis, and minimally stimulated endogenous
      cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF
      treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free
      medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed
      that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF
      treatment altered the mRNAs expression patterns of these cells. These data
      indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for
      myocardial repair by stimulating donor cell and endogenous cardiac stem cell
      survival, regeneration and promoting angiogenesis.

PMID- 24919181
TI  - Mapping large-area landscape suitability for honey bees to assess the influence
      of land-use change on sustainability of national pollination services.
AB  - Pollination is a critical ecosystem service affected by various drivers of land
      use change, such as policies and programs aimed at land resources, market values
      for crop commodities, local land-management decisions, and shifts in climate. The
      United States is the world's most active market for pollination services by honey
      bees, and the Northern Great Plains provide the majority of bee colonies used to
      meet the Nation's annual pollination needs. Legislation requiring increased
      production of biofuel crops, increasing commodity prices for crops of little
      nutritional value for bees in the Northern Great Plains, and reductions in
      government programs aimed at promoting land conservation are converging to alter
      the regional landscape in ways that challenge beekeepers to provide adequate
      numbers of hives for national pollination services. We developed a spatially
      explicit model that identifies sites with the potential to support large apiaries
      based on local-scale land-cover requirements for honey bees. We produced maps of
      potential apiary locations for North Dakota, a leading producer of honey, based
      on land-cover maps representing (1) an annual time series compiled from existing
      operational products and (2) a realistic scenario of land change. We found that
      existing land-cover products lack sufficient local accuracy to monitor actual
      changes in landscape suitability for honey bees, but our model proved informative
      for evaluating effects on suitability under scenarios of land change. The
      scenario we implemented was aligned with current drivers of land-use change in
      the Northern Great Plains and highlighted the importance of conservation lands in
      landscapes intensively and extensively managed for crops. 

PMID- 24919182
TI  - Hemoglobin oxygen affinity in patients with cystic fibrosis.
AB  - In patients with cystic fibrosis lung damages cause arterial hypoxia. As a
      typical compensatory reaction one might expect changes in oxygen affinity of
      hemoglobin. Therefore position (standard half saturation pressure P50st) and
      slope (Hill's n) of the O2 dissociation curve as well as the Bohr coefficients
      (BC) for CO2 and lactic acid were determined in blood of 14 adult patients (8
      males, 6 females) and 14 healthy controls (6 males, 8 females). While Hill's n
      amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1
      mmHg in both patient groups (controls male 26.7 +/- 0.2, controls female 27.0 +/-
      0.1, patients male 27.7 +/- 0.5, patients female 28.0 +/- 0.3 mmHg; mean and
      standard error, overall p<0.01). Main cause was a rise of 1-2 umol/g hemoglobin
      in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly
      identified as an outlier and with the mutation G551D, showed a reduction of both
      P50st (24.5 mmHg) and [2,3-biphosphoglycerate] (9.8 umol/g hemoglobin). There
      were no differences in BCCO2, but small sex differences in the BC for lactic acid
      in the controls which were not detectable in the patients. Causes for the right
      shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic
      glycolysis and an increased red cell turnover both causing increased [2,3
      biphosphoglycerate]. However, for situations with additional hypercapnia as
      observed in exercising patients a left shift seems to be a more favourable
      adaptation in cystic fibrosis. Additionally when in vivo PO2 values were
      corrected to the standard conditions they mostly lay left of the in vitro O2
      dissociation curve in both patients and controls. This hints to unknown fugitive
      factors influencing oxygen affinity.

PMID- 24919183
TI  - The morphologic and immunohistochemical spectrum of papillary renal cell
      carcinoma: study including 132 cases with pure type 1 and type 2 morphology as
      well as tumors with overlapping features.
AB  - Papillary renal cell carcinomas (pRCC) are classically divided into type 1 and 2
      tumors. However, many cases do not fulfill all the criteria for either type. We
      describe the clinical, morphologic, and immunohistochemical (IHC) features of 132
      pRCCs to better characterize the frequency and nature of tumors with overlapping
      features. Cases were reviewed and classified; IHC evaluation of CK7, EMA,
      TopoIIalpha, napsin A, and AMACR was performed on 95 cases. The frequencies of
      type 1, type 2, and "overlapping" pRCC were 25%, 28%, and 47%, respectively. The
      2 categories of "overlapping" tumors were: (1) cases with bland cuboidal cells
      but no basophilic cytoplasm (type A); and (2) cases with predominantly type 1
      histology admixed with areas showing prominent nucleoli (type B). The pathologic
      stage of "overlapping" cases showed concordance with type 1 tumors. Using the 2
      discriminatory markers (CK7, EMA), "type A" cases were similar to type 1.
      Although the high-nuclear grade areas of "type B" tumors showed some staining
      differences from their low-nuclear grade counterpart, their IHC profile was
      closer to type 1. Single nucleotide polymorphism array results, although
      preliminary and restricted to only 9 cases (3 with overlapping features), also
      seemed to confirm those findings. In conclusion, we demonstrate that variations
      in cytoplasmic quality and/or presence of high-grade nuclei in tumors otherwise
      displaying features of type 1 pRCCs are similar in stage and IHC profile those
      with classic type 1 histology, suggesting that their spectrum might be wider than
      originally described.

PMID- 24919184
TI  - External validation of a prognostic model for seizure recurrence following a
      first unprovoked seizure and implications for driving.
AB  - OBJECTIVE: In the United Kingdom and other European Union countries guidelines
      for driving following a first unprovoked seizure require the risk of another
      seizure in the next year to be less than 20%. Using data from one clinical trial,
      we previously developed a prognostic model to inform driving guidelines. The
      objective of this work is to externally validate our published model and
      demonstrate its generalisability. METHODS: A cohort of 620 people with a first
      unprovoked seizure was used to develop the original model which included
      variables for aetiology, first degree relative with epilepsy, seizures only while
      asleep, electroencephalogram, computed tomography or magnetic resonance scan
      result, and treatment policy. The validation cohorts consisted of 274 (United
      Kingdom), 305 (Italy), and 847 (Australia) people. The model was evaluated using
      discrimination and calibration methods. A covariate, missing from the Italian
      dataset, was handled via five imputation methods. Following external validation,
      the model was fitted to a pooled population comprising all validation datasets
      and the development dataset. The model was stratified by dataset. RESULTS: The
      model generalised relatively well. All methods of imputation performed fairly
      similarly. At six months, the risk of a seizure recurrence following a first ever
      seizure, based on the pooled datasets, is 15% (95% CI: (12% to 18%)) for patients
      who are treated immediately and 18% (95% CI: (15 to 21%)) otherwise. Individuals
      can be reliably stratified into risk groups according to the clinical factors
      included in the model. SIGNIFICANCE: Our prognostic model, used to inform driving
      regulations, has been validated and consequently has been proven as a valuable
      tool for predicting risk of seizure recurrence following a first seizure in
      people with various combinations of risk factors. Additionally, there is evidence
      to support one worldwide overall prognostic model for risk of second seizure
      following a first.

PMID- 24919186
TI  - Divergence in dialogue.
AB  - One of the best known claims about human communication is that people's behaviour
      and language use converge during conversation. It has been proposed that these
      patterns can be explained by automatic, cross-person priming. A key test case is
      structural priming: does exposure to one syntactic structure, in production or
      comprehension, make reuse of that structure (by the same or another speaker) more
      likely? It has been claimed that syntactic repetition caused by structural
      priming is ubiquitous in conversation. However, previous work has not tested for
      general syntactic repetition effects in ordinary conversation independently of
      lexical repetition. Here we analyse patterns of syntactic repetition in two large
      corpora of unscripted everyday conversations. Our results show that when lexical
      repetition is taken into account there is no general tendency for people to
      repeat their own syntactic constructions. More importantly, people repeat each
      other's syntactic constructions less than would be expected by chance; i.e.,
      people systematically diverge from one another in their use of syntactic
      constructions. We conclude that in ordinary conversation the structural priming
      effects described in the literature are overwhelmed by the need to actively
      engage with our conversational partners and respond productively to what they
      say. 

PMID- 24919185
TI  - Individual characteristics associated with mismatches between self-reported and
      accelerometer-measured physical activity.
AB  - BACKGROUND: Accurate assessment tools are required for the surveillance of
      physical activity (PA) levels and the assessment of the effect of interventions.
      In addition, increasing awareness of PA is often used as the first step in
      pragmatic behavioural interventions, as discrepancies between the amount of
      activity an individual perceives they do and the amount actually undertaken may
      act as a barrier to change. Previous research has demonstrated differences in the
      amount of activity individuals report doing, compared to their level of physical
      activity when measured with an accelerometer. Understanding the characteristics
      of those whose PA level is ranked differently when measured with either self
      report or accelerometry is important as it may inform the choice of instrument
      for future research. The aim of this project was to determine which individual
      characteristics are associated with differences between self-reported and
      accelerometer measured physical activity. METHODS: Participant data from the 2009
      wave of the Commuting and Health in Cambridge study were used. Quartiles of self
      reported and accelerometer-measured PA were derived by ranking each measure from
      lowest to highest. These quartiles were compared to determine whether
      individuals' physical activity was ranked higher by either method. Multinomial
      logistic regression models were used to investigate the individual
      characteristics associated with different categories of mismatch. RESULTS: Data
      from 486 participants (70% female) were included in the analysis. In adjusted
      analyses, the physical activity of overweight or obese individuals was
      significantly more likely to be ranked higher by self-report than by
      accelerometer than that of normal-weight individuals (OR = 2.07, 95%CI = 1.28
      3.34), particularly among women (OR = 3.97, 95%CI = 2.11-7.47). CONCLUSIONS:
      There was a greater likelihood of mismatch between self-reported and
      accelerometer measured physical activity levels in overweight or obese adults.
      Future studies in overweight or obese adults should consider employing both
      methods of measurement.

PMID- 24919187
TI  - Multiple measures of adiposity are associated with mean leukocyte telomere length
      in the northern Finland birth cohort 1966.
AB  - Studies of leukocyte telomere length (LTL) and adiposity have produced
      conflicting results, and the relationship between body mass index (BMI) and
      telomere length throughout life remains unclear. We therefore tested association
      of adult LTL measured in 5,598 participants with: i) childhood growth measures
      (BMI and age at adiposity rebound (AR)); ii) change in BMI from childhood to
      adulthood and iii) adult BMI, waist-to-hip ratio (WHR), body adiposity index
      (BAI). Childhood BMI at AR was positively associated with LTL at 31 years in
      women (P = 0.041). Adult BMI and WHR in both men (P = 0.025 and P = 0.049,
      respectively) and women (P = 0.029 and P = 0.008, respectively), and BAI in women
      (P = 0.021) were inversely associated with LTL at 31 years. An increase in
      standardised BMI between early childhood and adulthood was associated with
      shorter adult LTL in women (P = 0.008). We show that LTL is inversely associated
      with multiple measures of adiposity in both men and women. Additionally, BMI
      increase in women from childhood to adulthood is associated with shorter
      telomeres at age 31, potentially indicating accelerated biological ageing.

PMID- 24919188
TI  - Responses of a triple mutant defective in three iron deficiency-induced Basic
      Helix-Loop-Helix genes of the subgroup Ib(2) to iron deficiency and salicylic
      acid.
AB  - Plants are sessile organisms that adapt to external stress by inducing molecular
      and physiological responses that serve to better cope with the adverse growth
      condition. Upon low supply of the micronutrient iron, plants actively increase
      the acquisition of soil iron into the root and its mobilization from internal
      stores. The subgroup Ib(2) BHLH genes function as regulators in this response,
      however their concrete functions are not fully understood. Here, we analyzed a
      triple loss of function mutant of BHLH39, BHLH100 and BHLH101 (3xbhlh mutant). We
      found that this mutant did not have any iron uptake phenotype if iron was
      provided. However, under iron deficiency the mutant displayed a more severe leaf
      chlorosis than the wild type. Microarray-based transcriptome analysis revealed
      that this mutant phenotype resulted in the mis-regulation of 198 genes, out of
      which only 15% were associated with iron deficiency regulation itself. A detailed
      analysis revealed potential targets of the bHLH transcription factors as well as
      genes reflecting an exaggerated iron deficiency response phenotype. Since the
      BHLH genes of this subgroup have been brought into the context of the plant
      hormone salicylic acid, we investigated whether the 3xbhlh mutant might have been
      affected by this plant signaling molecule. Although a very high number of genes
      responded to SA, also in a differential manner between mutant and wild type, we
      did not find any indication for an association of the BHLH gene functions in SA
      responses upon iron deficiency. In summary, our study indicates that the bHLH
      subgroup Ib(2) transcription factors do not only act in iron acquisition into
      roots but in other aspects of the adaptation to iron deficiency in roots and
      leaves. 

PMID- 24919189
TI  - MicroRNA-328 inhibits renal tubular cell epithelial-to-mesenchymal transition by
      targeting the CD44 in pressure-induced renal fibrosis.
AB  - Epithelial-mesenchymal transition (EMT) occurs in stressed tubular epithelial
      cells, contributing to renal fibrosis. Initial mechanisms promoting EMT are
      unknown. Pressure force is an important mechanism contributing to the induction
      and progression of renal fibrogenesis in ureteric obstruction. In our study of
      cultured rat renal tubular cells (NRK-52E) under 60 mmHg of pressure, we found
      that the epithelial marker E-cadherin decreased and mesenchymal markers, e.g.,
      alpha-smooth muscle actin, fibronectin and Snail, increased. Pressure also
      induced the expression of connective tissue growth factor and transforming growth
      factor-beta. MicroRNA array assays showed that pressure reduced miR-328 at the
      initial stage of pressurization. We identified a potential target sequence of miR
      328 in rat CD44 3'-untranslated regions. In contrast with the miR-328 expression,
      CD44 expression was up-regulated at the initial pressurization stage. We also
      found that miR-328 expression decreased and CD44 increased in ureteric
      obstruction kidneys in the animal study. CD44 siRNA transfection significantly
      increased E-cadherin expression and inhibited pressure-induced EMT. Both
      hyaluronan binding peptide pep-1 and osteopontin neutralizing antibody inhibited
      pressure-induced EMT. Our results suggest that miR-328-mediated CD44 transient
      upregulation is an important trigger of the pressure-induced EMT in renal
      fibrosis. 

PMID- 24919190
TI  - Epigenetic regulations of immediate early genes expression involved in memory
      formation by the amyloid precursor protein of Alzheimer disease.
AB  - We previously demonstrated that APP epigenetically regulates Egr1 expression both
      in cultured neurons and in vivo. Since Egr1 is an immediate early gene involved
      in memory formation, we wondered whether other early genes involved in memory
      were regulated by APP and we studied molecular mechanisms involved. By comparing
      prefrontal (PF) cortex from wild type (APP+/+) and APP knockout mice (APP-/-), we
      observed that APP down regulates expression of four immediate early genes, Egr1,
      c-Fos, Bdnf and Arc. Down regulation of Egr1, c-Fos and Bdnf transcription
      resulted from a decreased enrichment of acetylated histone H4 on the
      corresponding gene promoter. Further characterization of H4 acetylation at Egr1
      and c-Fos promoters revealed increased acetylation of H4K5 and H4K12 residues in
      APP-/- mice. Whereas APP affected Egr1 promoter activity by reducing access of
      the CREB transcription factor, its effect on c-Fos appeared to depend on
      increased recruitment of HDAC2 histone deacetylase to the gene promoter. The
      physiological relevance of the epigenetic regulation of Egr1 and c-Fos gene
      transcription by APP was further analyzed following exposure of mice to novelty.
      Although transcription of Egr1 and c-Fos was increased following exposure of
      APP+/+ mice to novelty, such an induction was not possible in APP-/- mice with a
      high basal level of expression of these immediate early genes. Altogether, these
      results demonstrate that APP-mediated regulation of c-Fos and Egr1 by different
      epigenetic mechanisms is needed for their induction during exposure to novelty. 

PMID- 24919191
TI  - Secreted beta3-integrin enhances natural killer cell activity against acute
      myeloid leukemia cells.
AB  - Integrins are a large family of heterodimeric proteins that are involved in cell
      adhesion, migration, and proliferation. Integrin diversity and function is
      regulated by alternative splicing. Membrane-bound and truncated beta3-integrins
      were shown to be key players in cancer metastasis. However, the immunomodulatory
      functions of the soluble (s) beta3-integrin have not been investigated yet. In
      this study, we described a novel form of sbeta3-integrin in acute myeloid
      leukaemia (AML) patients. Furthermore, we assessed the role of the sbeta3
      integrin in the modulation of natural killer (NK)-cell activity. Levels of sbeta3
      integrin were analysed in plasma samples of 23 AML patients and 26 healthy donors
      by ELISA. The capacity of sbeta3-integrin to regulate NK cell activity was
      investigated using proliferation, cytokine secretion, and cytotoxicity assays.
      Circulating sbeta3-integrin was detected in the plasma of 8 AML patients. NK
      cells showed significantly higher proliferation rates after stimulation with
      sbeta3-integrin and IL-2, IL-15 (73%). Significant increases in the NK cells'
      secreted levels of TNF-alpha, IFN-gamma were measured in presence of sbeta3
      integrin. In addition, sbeta3-integrin caused the upregulation of Granzyme B
      transcripts levels as well as FasL expression levels in NK cells. Most
      importantly, significantly higher K562 or AML blast target cell lysis rates were
      observed when NK cells were exposed to sbeta3-integrin. This study reports the
      identification of a novel sbeta3-integrin in AML patients and provides novel
      insights into its role in the immunomodulation of NK cell activity. 

PMID- 24919192
TI  - Development of a novel multiplex PCR assay to detect functional subtypes of
      KIR3DL1 alleles.
AB  - Among NK cell receptor-ligand partnerships, KIR3DL1 and HLA-Bw4 demonstrate the
      greatest diversity; permutations of their allelic combinations titrate NK
      reactivity. Balancing selection has maintained distinct subtypes of KIR3DL1
      alleles in global populations, implying that each may provide unique fitness
      advantages and variably influence disease processes. Though approaches exist for
      determining HLA-B allotypes, practical methods for identifying KIR3DL1 alleles
      are lacking. We have developed a PCR-based approach that identifies functional
      subtypes of KIR3DL1 alleles; it is suitable for research and may have clinical
      application. Six allele subsets were identified based on expression
      characteristics of the eleven most common KIR3DL1 alleles represented in reported
      populations. The remaining 62 low-frequency alleles were distributed into these
      groups based on sequence homology to coding regions. Subtype-specific SNPs were
      found in exons 3, 4, and 7, and used as priming sites for five multiplex PCR
      reactions. Genomic DNA derived from 175 unrelated donors and 52 related
      individuals from 6 families demonstrated >99.5% concordance between sequence
      based typing and our novel approach. Finally, PCR-based typing accurately
      predicted NK phenotypes obtained by flow cytometry after staining with DX9 and
      Z27 monoclonal antibodies. This novel approach facilitates high-throughput
      analysis of KIR3DL1 allotypes to enable a broader understanding of KIR3DL1 and
      HLA-Bw4 interaction in health and disease. 

PMID- 24919194
TI  - The added value of water footprint assessment for national water policy: a case
      study for Morocco.
AB  - A Water Footprint Assessment is carried out for Morocco, mapping the water
      footprint of different activities at river basin and monthly scale,
      distinguishing between surface- and groundwater. The paper aims to demonstrate
      the added value of detailed analysis of the human water footprint within a
      country and thorough assessment of the virtual water flows leaving and entering a
      country for formulating national water policy. Green, blue and grey water
      footprint estimates and virtual water flows are mainly derived from a previous
      grid-based (5 * 5 arc minute) global study for the period 1996-2005. These
      estimates are placed in the context of monthly natural runoff and waste
      assimilation capacity per river basin derived from Moroccan data sources. The
      study finds that: (i) evaporation from storage reservoirs is the second largest
      form of blue water consumption in Morocco, after irrigated crop production; (ii)
      Morocco's water and land resources are mainly used to produce relatively low
      value (in US$/m3 and US$/ha) crops such as cereals, olives and almonds; (iii)
      most of the virtual water export from Morocco relates to the export of products
      with a relatively low economic water productivity (in US$/m3); (iv) blue water
      scarcity on a monthly scale is severe in all river basins and pressure on
      groundwater resources by abstractions and nitrate pollution is considerable in
      most basins; (v) the estimated potential water savings by partial relocation of
      crops to basins where they consume less water and by reducing water footprints of
      crops down to benchmark levels are significant compared to demand reducing and
      supply increasing measures considered in Morocco's national water strategy.

PMID- 24919195
TI  - Low-dose high-pitch CT angiography of the supraaortic arteries using sinogram
      affirmed iterative reconstruction.
AB  - OBJECTIVE: To prospectively evaluate image quality and radiation dose using a low
      dose computed tomography angiography protocol and iterative image reconstruction
      for high-pitch dual-source CT-angiography (DSCTA) of the supraaortic arteries.
      MATERIAL AND METHODS: DSCTA was performed in 42 patients, using either 120 kVp
      tube voltage, 120 mAS tube current, 2.4 pitch and filtered back projection, or
      100 kVp tube voltage, 100 mAs tube current, 3.2 pitch, and sinogram affirmed
      iterative reconstruction. Measurements of vessel attenuation, of the contrast-to
      noise ratio (CNR) and the signal-to-noise ratio (SNR) were performed to
      objectively evaluate image quality. Two readers evaluated subjective image
      quality and image noise, using a four-point scale. Effective dose was used to
      compare the differences in radiation dose. RESULTS: Low-dose protocol application
      showed significantly higher vessel opacification (p = 0.013), and non
      significantly higher CNR and SNR values. There was no difference in the
      subjective image quality and image noise reading between the protocols. Effective
      dose was significantly lower using the low-dose protocol (1.29 +/- 0.21 mSv vs.
      2.92 +/- 0.72 mSv; p < 0.001). CONCLUSION: The combined use of reduced tube
      voltage, reduced tube current, and iterative reconstruction reduces radiation
      dose by 55.4% in high-pitch DSCTA of the supraaortic arteries without impairment
      of image quality.

PMID- 24919196
TI  - A TRIP230-retinoblastoma protein complex regulates hypoxia-inducible factor
      1alpha-mediated transcription and cancer cell invasion.
AB  - Localized hypoxia in solid tumors activates transcriptional programs that promote
      the metastatic transformation of cells. Like hypoxia-inducible hyper
      vascularization, loss of the retinoblastoma protein (Rb) is a trait common to
      advanced stages of tumor progression in many metastatic cancers. However, no link
      between the role of Rb and hypoxia-driven metastatic processes has been
      established. We demonstrated that Rb is a key mediator of the hypoxic response
      mediated by HIF1alpha/beta, the master regulator of the hypoxia response, and its
      essential co-activator, the thyroid hormone receptor/retinoblastoma-interacting
      protein (TRIP230). Furthermore, loss of Rb unmasks the full co-activation
      potential of TRIP230. Using small inhibitory RNA approaches in vivo, we
      established that Rb attenuates the normal physiological response to hypoxia by
      HIF1alpha. Notably, loss of Rb results in hypoxia-dependent biochemical changes
      that promote acquisition of an invasive phenotype in MCF7 breast cancer cells. In
      addition, Rb is present in HIF1alpha-ARNT/HIF1beta transcriptional complexes
      associated with TRIP230 as determined by co-immuno-precipitation, GST-pull-down
      and ChIP assays. These results demonstrate that Rb is a negative modulator of
      hypoxia-regulated transcription by virtue of its direct effects on the HIF1
      complex. This work represents the first link between the functional ablation of
      Rb in tumor cells and HIF1alpha-dependent transcriptional activation and
      invasion. 

PMID- 24919197
TI  - RhoA/ROCK signaling and pleiotropic alpha1A-adrenergic receptor regulation of
      cardiac contractility.
AB  - AIMS: To determine the mechanisms by which the alpha1A-adrenergic receptor (AR)
      regulates cardiac contractility. BACKGROUND: We reported previously that
      transgenic mice with cardiac-restricted alpha1A-AR overexpression (alpha1A-TG)
      exhibit enhanced contractility but not hypertrophy, despite evidence implicating
      this Galphaq/11-coupled receptor in hypertrophy. METHODS: Contractility, calcium
      (Ca(2+)) kinetics and sensitivity, and contractile proteins were examined in
      cardiomyocytes, isolated hearts and skinned fibers from alpha1A-TG mice (170-fold
      overexpression) and their non-TG littermates (NTL) before and after alpha1A-AR
      agonist stimulation and blockade, angiotensin II (AngII), and Rho kinase (ROCK)
      inhibition. RESULTS: Hypercontractility without hypertrophy with alpha1A-AR
      overexpression is shown to result from increased intracellular Ca(2+) release in
      response to agonist, augmenting the systolic amplitude of the intracellular
      Ca(2+) concentration [Ca(2+)]i transient without changing resting [Ca(2+)]i. In
      the absence of agonist, however, alpha1A-AR overexpression reduced contractility
      despite unchanged [Ca(2+)]i. This hypocontractility is not due to heterologous
      desensitization: the contractile response to AngII, acting via its Galphaq/11
      coupled receptor, was unaltered. Rather, the hypocontractility is a pleiotropic
      signaling effect of the alpha1A-AR in the absence of agonist, inhibiting
      RhoA/ROCK activity, resulting in hypophosphorylation of both myosin phosphatase
      targeting subunit 1 (MYPT1) and cardiac myosin light chain 2 (cMLC2), reducing
      the Ca(2+) sensitivity of the contractile machinery: all these effects were
      rapidly reversed by selective alpha1A-AR blockade. Critically, ROCK inhibition in
      normal hearts of NTLs without alpha1A-AR overexpression caused
      hypophosphorylation of both MYPT1 and cMLC2, and rapidly reduced basal
      contractility. CONCLUSIONS: We report for the first time pleiotropic alpha1A-AR
      signaling and the physiological role of RhoA/ROCK signaling in maintaining
      contractility in the normal heart.

PMID- 24919198
TI  - BRCA1 silencing is associated with failure of DNA repairing in retinal
      neurocytes.
AB  - Retinal post-mitotic neurocytes display genomic instability after damage induced
      by physiological or pathological factors. The involvement of BRCA1, an important
      factor in development and DNA repair in mature retinal neurocytes remains
      unclear. Thus, we investigated the developmental expression profile of BRCA1 in
      the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our
      data show the expression of BRCA1 is developmentally down-regulated in the
      retinas of mice after birth. Similarly, BRCA1 is down-regulated after
      differentiation induced by TSA in retinal precursor cells. An end-joining
      activity assay and DNA fragmentation analysis indicated that the DNA repair
      capacity is significantly reduced. Moreover, DNA damage in differentiated cells
      or cells in which BRCA1 is silenced by siRNA interference is more extensive than
      that in precursor cells subjected to ionizing radiation. To further investigate
      non-homologous end joining (NHEJ), the major repair pathway in non-divided
      neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks
      are generated by I-SceI. Our data showed that differentiation and the down
      regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in
      the total NHEJ frequency compared with that in cells with normal BRCA1.
      Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate
      indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as
      expected, the down-regulation of BRCA1 significantly inhibits the viability of
      retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical
      role in retinal development and repairs DNA damage of mature retina neurocytes. 

PMID- 24919200
TI  - L(p) -norm IDF for scalable image retrieval.
AB  - The inverse document frequency (IDF) is prevalently utilized in the bag-of-words
      based image retrieval application. The basic idea is to assign less weight to
      terms with high frequency, and vice versa. However, in the conventional IDF
      routine, the estimation of visual word frequency is coarse and heuristic.
      Therefore, its effectiveness is largely compromised and far from optimal. To
      address this problem, this paper introduces a novel IDF family by the use of Lp
      norm pooling technique. Carefully designed, the proposed IDF considers the term
      frequency, document frequency, the complexity of images, as well as the codebook
      information. We further propose a parameter tuning strategy, which helps to
      produce optimal balancing between TF and pIDF weights, yielding the so-called Lp
      norm IDF (pIDF). We show that the conventional IDF is a special case of our
      generalized version, and two novel IDFs, i.e., the average IDF and the max IDF,
      can be defined from the concept of pIDF. Further, by counting for the term
      frequency in each image, the proposed pIDF helps to alleviate the visual word
      burstiness phenomenon. Our method is evaluated through extensive experiments on
      four benchmark data sets (Oxford 5K, Paris 6K, Holidays, and Ukbench). We show
      that the pIDF works well on large scale databases and when the codebook is
      trained on irrelevant data. We report an mean average precision improvement of as
      large as +13.0% over the baseline TF-IDF approach on a 1M data set. In addition,
      the pIDF has a wide application scope varying from buildings to general objects
      and scenes. When combined with postprocessing steps, we achieve competitive
      results compared with the state-of-the-art methods. In addition, since the pIDF
      is computed offline, no extra computation or memory cost is introduced to the
      system at all. 

PMID- 24919199
TI  - National economic development and disparities in body mass index: a cross
      sectional study of data from 38 countries.
AB  - BACKGROUND: Increases in body mass index (BMI) and the prevalence of overweight
      in low- and middle income countries (LMICs) are often ascribed to changes in
      global trade patterns or increases in national income. These changes are likely
      to affect populations within LMICs differently based on their place of residence
      or socioeconomic status (SES). OBJECTIVE: Using nationally representative survey
      data from 38 countries and national economic indicators from the World Bank and
      other international organizations, we estimated ecological and multilevel models
      to assess the association between national levels of gross domestic product
      (GDP), foreign direct investment (FDI), and mean tariffs and BMI. DESIGN: We used
      linear regression to estimate the ecological association between average annual
      change in economic indicators and BMI, and multilevel linear or ordered
      multinomial models to estimate associations between national economic indicators
      and individual BMI or over- and underweight. We also included cross-level
      interaction terms to highlight differences in the association of BMI with
      national economic indicators by type of residence or socioeconomic status (SES).
      RESULTS: There was a positive but non-significant association of GDP and mean
      BMI. This positive association of GDP and BMI was greater among rural residents
      and the poor. There were no significant ecological associations between measures
      of trade openness and mean BMI, but FDI was positively associated with BMI among
      the poorest respondents and in rural areas and tariff levels were negatively
      associated with BMI among poor and rural respondents. CONCLUSION: Measures of
      national income and trade openness have different associations with the BMI
      across populations within developing countries. These divergent findings
      underscore the complexity of the effects of development on health and the
      importance of considering how the health effects of "globalizing" economic and
      cultural trends are modified by individual-level wealth and residence.

PMID- 24919201
TI  - Efficient hybrid tree-based stereo matching with applications to postcapture
      image refocusing.
AB  - Estimating dense correspondence or depth information from a pair of stereoscopic
      images is a fundamental problem in computer vision, which finds a range of
      important applications. Despite intensive past research efforts in this topic, it
      still remains challenging to recover the depth information both reliably and
      efficiently, especially when the input images contain weakly textured regions or
      are captured under uncontrolled, real-life conditions. Striking a desired balance
      between computational efficiency and estimation quality, a hybrid minimum
      spanning tree-based stereo matching method is proposed in this paper. Our method
      performs efficient nonlocal cost aggregation at pixel-level and region-level, and
      then adaptively fuses the resulting costs together to leverage their respective
      strength in handling large textureless regions and fine depth discontinuities.
      Experiments on the standard Middlebury stereo benchmark show that the proposed
      stereo method outperforms all prior local and nonlocal aggregation-based methods,
      achieving particularly noticeable improvements for low texture regions. To
      further demonstrate the effectiveness of the proposed stereo method, also
      motivated by the increasing desire to generate expressive depth-induced photo
      effects, this paper is tasked next to address the emerging application of
      interactive depth-of-field rendering given a real-world stereo image pair. To
      this end, we propose an accurate thin-lens model for synthetic depth-of-field
      rendering, which considers the user-stroke placement and camera-specific
      parameters and performs the pixel-adapted Gaussian blurring in a principled way.
      Taking ~1.5 s to process a pair of 640*360 images in the off-line step, our
      system named Scribble2focus allows users to interactively select in-focus regions
      by simple strokes using the touch screen and returns the synthetically refocused
      images instantly to the user. 

PMID- 24919203
TI  - ProMT: effective human promoter prediction using Markov chain model based on DNA
      structural properties.
AB  - The core promoters play significant and extensive roles for the initiation and
      regulation of DNA transcription. The identification of core promoters is one of
      the most challenging problems yet. Due to the diverse nature of core promoters,
      the results obtained through existing computational approaches are not
      satisfactory. None of them considered the potential influence on performance of
      predictive approach resulted by the interference between neighboring TSSs in TSS
      clusters. In this paper, we sufficiently considered this main factor and proposed
      an approach to locate potential TSS clusters according to the correlation of
      regional profiles of DNA and TSS clusters. On this basis, we further presented a
      novel computational approach (ProMT) for promoter prediction using Markov chain
      model and predictive TSS clusters based on structural properties of DNA.
      Extensive experiments demonstrated that ProMT can significantly improve the
      predictive performance. Therefore, considering interference between neighboring
      TSSs is essential for a wider range of promoter prediction. 

PMID- 24919202
TI  - Human movement training with a cable driven ARm EXoskeleton (CAREX).
AB  - In recent years, the authors have proposed lightweight exoskeleton designs for
      upper arm rehabilitation using multi-stage cable-driven parallel mechanism.
      Previously, the authors have demonstrated via experiments that it is possible to
      apply "assist-as-needed" forces in all directions at the end-effector with such
      an exoskeleton acting on an anthropomorphic machine arm. A human-exoskeleton
      interface was also presented to show the feasibility of CAREX on human subjects.
      The goals of this paper are to 1) further address issues when CAREX is mounted on
      human subjects, e.g., generation of continuous cable tension trajectories 2)
      demonstrate the feasibility and effectiveness of CAREX on movement training of
      healthy human subjects and a stroke patient. In this research, CAREX is rigidly
      attached to an arm orthosis worn by human subjects. The cable routing points are
      optimized to achieve a relatively large "tensioned" static workspace. A new cable
      tension planner based on quadratic programming is used to generate continuous
      cable tension trajectory for smooth motion. Experiments were carried out on eight
      healthy subjects. The experimental results show that CAREX can help the subjects
      move closer to a prescribed circular path using the force fields generated by the
      exoskeleton. The subjects also adapt to the path shortly after training. CAREX
      was also evaluated on a stroke patient to test the feasibility of its use on
      patients with neural impairment. The results show that the patient was able to
      move closer to a prescribed straight line path with the "assist-as-needed" force
      field. 

PMID- 24919204
TI  - Residual stenosis estimation of arteriovenous grafts using a dual-channel
      phonoangiography with fractional-order features.
AB  - The residual stenosis estimation of an arteriovenous shunt is a valuable for
      evaluating outcomes of percutaneous transluminal angioplasty (PTA) treatment and
      surgical revision. This paper proposes a dual-channel phonoangiography (PCG) with
      fractional-order features to estimate the residual of stenosis estimation of
      arteriovenous shunt. The auscultation technique provides a noninvasive tool to
      monitor the degrees of arteriovenous grafts (AVGs). Then, support methods, such
      as the Burg autoregressive (AR) method and self-synchronization error formulation
      (SSEF), are used to extract fractional-order features between the loop site (L
      site) and venous anastomosis site (V-site). Using 2-D patterns (nonlinear
      mapping), a generalized regression neural network (GRNN) is designed as a
      nonlinear estimate model to indicate the outcome of surgical revision or AVG
      stenosis upon routine monthly examinations. For 42 long-term follow-up patients,
      the results of examination show the proposed GRNN-based screening model
      efficiently estimates residual stenosis. 

PMID- 24919205
TI  - Improving the recognition of eating gestures using intergesture sequential
      dependencies.
AB  - This paper considers the problem of recognizing eating gestures by tracking wrist
      motion. Eating gestures are activities commonly undertaken during the consumption
      of a meal, such as sipping a drink of liquid or using utensils to cut food. Each
      of these gestures causes a pattern of wrist motion that can be tracked to
      automatically identify the activity. Previous works have studied this problem at
      the level of a single gesture. In this paper, we demonstrate that individual
      gestures have sequential dependence. To study this, three types of classifiers
      were built: 1) a K-nearest neighbor classifier which uses no sequential context,
      2) a hidden Markov model (HMM) which captures the sequential context of
      subgesture motions, and 3) HMMs that model intergesture sequential dependencies.
      We built first-order to sixth-order HMMs to evaluate the usefulness of increasing
      amounts of sequential dependence to aid recognition. On a dataset of 25 meals, we
      found that the baseline accuracies for the KNN and the subgesture HMM classifiers
      were 75.8% and 84.3%, respectively. Using HMMs that model intergesture sequential
      dependencies, we were able to increase accuracy to up to 96.5%. These results
      demonstrate that sequential dependencies exist between eating gestures and that
      they can be exploited to improve recognition accuracy. 

PMID- 24919206
TI  - Relative saliency model over multiple images with an application to yarn surface
      evaluation.
AB  - Saliency models have been developed and widely demonstrated to benefit
      applications in computer vision and image understanding. In most of existing
      models, saliency is evaluated within an individual image. That is, saliency value
      of an item (object/region/pixel) represents the conspicuity of it as compared
      with the remaining items in the same image. We call this saliency as absolute
      saliency, which is uncomparable among images. However, saliency should be
      determined in the context of multiple images for some visual inspection tasks.
      For example, in yarn surface evaluation, saliency of a yarn image should be
      measured with regard to a set of graded standard images. We call this saliency
      the relative saliency, which is comparable among images. In this paper, a study
      of visual attention model for comparison of multiple images is explored, and a
      relative saliency model of multiple images is proposed based on a combination of
      bottom-up and top-down mechanisms, to enable relative saliency evaluation for the
      cases where other image contents are involved. To fully characterize the
      differences among multiple images, a structural feature extraction strategy is
      proposed, where two levels of feature (high-level, low-level) and three types of
      feature (global, local-local, local-global) are extracted. Mapping functions
      between features and saliency values are constructed and their outputs reflect
      relative saliency for multiimage contents instead of single image content. The
      performance of the proposed relative saliency model is well demonstrated in a
      yarn surface evaluation. Furthermore, the eye tracking technique is employed to
      verify the proposed concept of relative saliency for multiple images. 

PMID- 24919207
TI  - Fault detection for T-S fuzzy time-delay systems: delta operator and input-output
      methods.
AB  - This paper focuses on the problem of fault detection for Takagi-Sugeno fuzzy
      systems with time-varying delays via delta operator approach. By designing a
      filter to generate a residual signal, the fault detection problem addressed in
      this paper can be converted into a filtering problem. The time-varying delay is
      approximated by the two-term approximation method. Fuzzy augmented fault
      detection system is constructed in delta -domain, and a threshold function is
      given. By applying the scaled small gain theorem and choosing a Lyapunov
      Krasovskii functional in delta -domain, a sufficient condition of asymptotic
      stability with a prescribed Hinfinity disturbance attenuation level is derived
      for the proposed fault detection system. Then, a solvability condition for the
      designed fault detection filter is established, with which the desired filter can
      be obtained by solving a convex optimization problem. Finally, an example is
      given to demonstrate the feasibility and effectiveness of the proposed method. 

PMID- 24919208
TI  - Dynamic adjustment of hidden node parameters for extreme learning machine.
AB  - Extreme learning machine (ELM), proposed by Huang et al., was developed for
      generalized single hidden layer feedforward networks with a wide variety of
      hidden nodes. ELMs have been proved very fast and effective especially for
      solving function approximation problems with a predetermined network structure.
      However, it may contain insignificant hidden nodes. In this paper, we propose
      dynamic adjustment ELM (DA-ELM) that can further tune the input parameters of
      insignificant hidden nodes in order to reduce the residual error. It is proved in
      this paper that the energy error can be effectively reduced by applying recursive
      expectation-minimization theorem. In DA-ELM, the input parameters of
      insignificant hidden node are updated in the decreasing direction of the energy
      error in each step. The detailed theoretical foundation of DA-ELM is presented in
      this paper. Experimental results show that the proposed DA-ELM is more efficient
      than the state-of-art algorithms such as Bayesian ELM, optimally-pruned ELM, two
      stage ELM, Levenberg-Marquardt, sensitivity-based linear learning method as well
      as the preliminary ELM. 

PMID- 24919209
TI  - [Prevalence of protein-energy undernutrition evaluated by the measurement of
      triceps skinfold thickness and mid-arm muscle circumference of 103 adults with
      cirrhosis of the liver hospitalized in the department of hepatology and
      gastroenterology of the Lome Campus University Hospital (Togo)].
AB  - OBJECTIVE: To evaluate by a reliable method the protein-energy nutritional status
      of adults hospitalized in the hepatology and gastroenterology department of the
      Lome Campus University Hospital. METHODS: This cross-sectional prospective study
      conducted from March 1 to September 15, 2012, included 103 inpatients aged at
      least 16 years. The variables evaluated were: triceps skinfold thickness (TST),
      mid-arm muscle circumference (MAMC), serum albumin, CRP, and orosomucoid. The
      Child-Pugh classification was used to evaluate the clinical severity of liver
      disease. RESULTS: Within this population of patients with cirrhosis, 40 were
      alcohol-dependent (39.0%) and 85 had anorexia (82.5%); 49 were in group B of the
      Child-Pugh classification, and 37 in group C. We found a non-significant (p =
      0.324) difference in TST measurement between the three Child-Pugh groups: A (8.4
      +/- 4.5); B (6.1 +/- 3.7); and C (6.4 +/- 7.2). The prevalence of protein-energy
      malnutrition ranged from 52.0% to 82.5%, when evaluated by MAMC or TST. Our
      results confirm the need to pay additional attention to the protein-energy
      nutritional status of inpatients in this department, by adding reliable tools,
      such as the TST and MAMC, to the biochemistry analysis to characterize
      undernutrition.

PMID- 24919210
TI  - [Etiology of vaginal infections in Ouagadougou (Burkina Faso)].
AB  - OBJECTIVE: to determine the specific antimicrobial activity of the drugs proposed
      in the national algorithm for treatment of vaginal infections. METHOD: Over a
      three-month period, the bacteriological laboratory of the Yalgado-Ouedraogo
      University Hospital in Ouagadougou analyzed vaginal swabs from women seen at 5
      health-care facilities in that city. RESULT: The study included 404 women with a
      mean age of 29 years. The microbes with the highest incidence rates were various
      species of Candida (20%), Gardnerella and/or Mobiluncus (18.8%), and
      Ureaplasma/Mycoplasma (10.9%). The agents isolated were highly susceptible to
      ciprofloxacin, erythromycin, fluconazole, miconazole, and nystatin. CONCLUSION:
      This study demonstrated the continuing efficacy of the drugs in the national
      algorithm for treatment of vaginal infections, which is associated with
      compliance with the recommended diagnostic procedure and therapeutic protocol.

PMID- 24919211
TI  - [Exercise-induced left bundle branch block with chest pain related to
      antimalarial prophylaxis with chloroquine].
AB  - Left bundle branch block (LBBB) during exercise can be associated with chest
      pain. Though this association is mostly correlated with an underlying coronary
      artery disease, painful LBBB has been described in patients with normal coronary
      arteries. We report a case of exercise-induced LBBB with typical angina pectoris
      related to antimalarial prophylaxis with chloroquine in a 66-year old woman with
      normal coronary arteries, which was reversed after treatment discontinuation. The
      effect of chloroquine on the electrophysiological properties of nodal cardiac
      tissue is responsible for this rate-dependent LBBB. Precautions for future
      antimalarial prophylaxis are also discussed. 

PMID- 24919213
TI  - In memoriam: Mavis P. Kelsey, Sr. (1912-2013).

PMID- 24919212
TI  - [Treatment of uterine synechiae without hysteroscopy in a semiurban setting in
      Cameroon].
AB  - We evaluated the outcome of treatment of uterine synechiae (or adhesions, also
      known as Asherman syndrome) by cervical dilatation and sequential estrogen and
      progestogen administration for three months. This retrospective cohort study
      examined records of 86 women with infertility or menstrual disorders or both and
      treated from October 2004 to November 2011 for synechiae diagnosed by
      hysterosalpingography. The data analyzed included age, presenting complaint, and
      treatment outcome. During the study period, 86 women were seen for uterine
      synechiae but only 81 files could be included. The patients' mean age was 25.52
      (range: 19-40 years), with 37% in the age group of 25-29 years. Of these 82
      women, 71 reported menstrual disorders and 60 infertility. After treatment, 11/60
      (18%) became pregnant and 35/71 (49%) recovered normal menstrual profiles. The
      reference treatment for uterine synechiae is hysteroscopy, which yields good
      results. In poor settings, however, hysteroscopy remains inaccessible, and the
      old method of cervical dilation and sequential estrogen and progestogen therapy
      is an acceptable alternative.

PMID- 24919214
TI  - Considerations for diagnosis and management of ileostomy-related malignancy: a
      report of two cases.
AB  - Malignancy associated with a long-standing ileostomy is a rare occurrence
      reported as early as 3 years after ileostomy placement. Patients most commonly
      present first to their ostomy care nurse with peristomal skin changes
      unresponsive to conservative measures. To elucidate presentation and management,
      two cases of male patients with ileostomy-related with malignancy (one lymphoma
      and one squamous cell carcinoma) are discussed. Both patients had undergone
      proctocolectomy with end ileostomy decades prior. Symptoms in the lymphoma
      patient included complaints of skin irritation, stoma mucosa changes and
      friability, and a persistent rash around the ostomy; he was found to have small
      bowel friability and a peristomal mass arising from the terminal ileum that was
      resected en bloc with the ileostomy, the surrounding skin, and associated
      abdominal wall musculature. The patient with squamous cell carcinoma had
      developed a gray-tan skin lesion around his ileostomy site; he underwent
      exploratory laparotomy with wide local excision of the abdominal wall including
      ileostomy site, distal ileum, and squamous cell carcinoma, and resiting of the
      ileostomy to the contralateral abdominal wall. Ostomy care providers should be
      aware of the clinical presentation of ostomy-associated malignancy to ensure
      thorough evaluation and prompt referral for surgical management are provided.

PMID- 24919215
TI  - Differentiating ultrasound technologies. Reply.

PMID- 24919216
TI  - Keeping the quest in our questions.

PMID- 24919217
TI  - Don't give up on that wound--a palliative care perspective.

PMID- 24919218
TI  - [Advancement of researches on association of non-alcoholic fatty liver disease
      with type 2 diabetes mellitus].

PMID- 24919219
TI  - [The relationship between thyroid dysfunction and liver].

PMID- 24919220
TI  - [The effects of liver disease on endocrine hormone].

PMID- 24919222
TI  - [Diabetes with liver disease: mechanism and management].

PMID- 24919221
TI  - [Effectiveness of genetic nasal spray of fluticasone propionate ester].

PMID- 24919223
TI  - [The role of antidiabetic drugs in patients with non-alcoholic fatty liver
      disease].

PMID- 24919224
TI  - [Progress in the study of nonalcoholic fatty liver disease: insights from
      research in 2013].

PMID- 24919225
TI  - [Analysis of hepatitis B virus mutations in 20 patients with HBV-related acute-on
      chronic liver failure and 19 patients with chronic hepatitis B].

PMID- 24919226
TI  - [Analysis of liver specimen quality using 280 specimens obtained by routine
      puncture biopsy].

PMID- 24919227
TI  - [IIn-line X-ray phase-contrast imaging of human hepatocellular carcinoma
      microvasculature ex vivo].

PMID- 24919228
TI  - [Report of two cases of hepatitis B virus reactivation in primary liver carcinoma
      patients treated with the FOLFOX chemotherapy regimen].

PMID- 24919229
TI  - [Caspofungin and voriconazole combination therapy for invasive pulmonary
      aspergillosis in patients with liver failure: a report of two cases].

PMID- 24919230
TI  - Appropriate use of bibliometric indicators for the assessment of journals,
      research proposals, and individuals.

PMID- 24919231
TI  - Sensitive ligand-based protein quantification using immuno-PCR: A critical review
      of single-probe and proximity ligation assays.
AB  - Quantitative PCR (qPCR) of reverse-transcribed mRNA has revolutionized gene
      expression analyses. qPCR analysis is based on the prevalent assumption that mRNA
      transcript numbers provide an adequate measure of specific biomarker expression.
      However, taking the complexity of protein turnover into account, there is a need
      to correlate qPCR-derived transcriptional patterns with protein translational
      patterns so as to not leave behind important pathobiological details. One
      emerging approach in protein analysis is PCR-coupled protein quantification,
      often denoted as immuno-PCR (iPCR), which targets soluble proteins. Here we
      review recent trends and applications in iPCR assays that may bridge the gap
      between classical enzyme-linked immunosorbent assays and mass spectrometry
      methodologies in terms of sensitivity and multiplexing.

PMID- 24919232
TI  - Case study. A fading decision. Commentary.

PMID- 24919233
TI  - Case study. A fading decision. Commentary.

PMID- 24919234
TI  - Case study. A fading decision. Commentary.

PMID- 24919235
TI  - MOM is coming to Indiana.

PMID- 24919236
TI  - The dental heart.

PMID- 24919237
TI  - IndianaMOM charitable event has a multiplier effect.

PMID- 24919238
TI  - DHATs.

PMID- 24919239
TI  - Three ways to better manage overhead.

PMID- 24919240
TI  - Implant solutions for the implant patient: diagnosis and treatment planning for
      predictable results.

PMID- 24919241
TI  - Old wives' tales and the Coriolis Effect.

PMID- 24919242
TI  - A few thoughts: get outside, slow down, take a nap, and don't forget to breathe.

PMID- 24919243
TI  - Reasons for not seeking care for urinary incontinence in older community-dwelling
      women: a contemporary review.
AB  - Urinary incontinence (UI) is a reality for many women and can have a significant
      impact on quality of life. However, rates of seeking care for UI are low. This
      literature review compiles current research examining themes related to care
      seeking behavior of older adult community-dwelling women, identifies any gaps in
      the recent literature, and provides suggestions for future research directions.

PMID- 24919244
TI  - Indwelling urinary catheters: pattern of use in a public tertiary-level
      Australian hospital.
AB  - An audit of charts from patients identified as having an indwelling urinary
      catheter (IDC) was conducted in a 450-bed, tertiary level hospital (Concord
      Repatriation General Hospital) in Australia. Documentation of relevant
      information regarding IDC in the medical record included indication for
      catheterization, insertion and removal dates, use of antibiotics, place of
      insertion, designation of inserter, catheter type, availability of IDC kits, and
      use of catheter fixation devices.

PMID- 24919245
TI  - A case report and review of transitional cell carcinoma in children.
AB  - Transitional cell carcinoma (TCC) is a rare cause of hematuria in children. This
      type of urothelial bladder tumor is typically low grade and carries a good
      prognosis. In this article, a case report is presented along with a review of the
      literature on TCC in children.

PMID- 24919246
TI  - Cancer patients' perspectives on multidisciplinary team working: an exploratory
      focus group study.
AB  - This qualitative, focus-group study explores what patients understand about the
      multidisciplinary team (MDT) in cancer care. Participants were positive towards
      MDT working, and by strengthening the role of nurses in MDT decision-making, the
      representation of patients' interests can be improved.

PMID- 24919247
TI  - Adding to the evidence base: cancer patients' perspectives on multidisciplinary
      team working: an exploratory focus group study.

PMID- 24919248
TI  - Initial experience of intravesical gemcitabine for patients with high-risk
      superficial transitional cell carcinoma of the bladder following BCG failure.
AB  - This study reports the use of intravesical gemcitabine in managing patients with
      high-risk bladder cancer, refractory to Bacillus Calmette-Guerin (BCG). Patients
      were given gemcitibine; treatment response was evaluated by fluorescence
      cystoscopy biopsy and urine cytology. Time to reoccurrence increased with
      instillation time.

PMID- 24919249
TI  - An interview with Gail Warden.

PMID- 24919250
TI  - Reducing avoidable hospital readmissions effectively: a statewide campaign.
AB  - BACKGROUND: The Reducing Avoidable Readmissions Effectively (RARE) Campaign was
      designed to engage hospitals and care providers in Minnesota across the continuum
      of care to prevent avoidable hospital readmissions within 30 days of hospital
      discharge. METHODS: Support for hospitals was provided on a one-on-one basis by a
      RARE resource consultant, as well as through the campaign website and a monthly
      newsletter. Hospitals had the opportunity to participate in any of three learning
      collaboratives-Care Transitions Intervention, Project RED (ReEngineered
      Discharge), or SAFE Transitions of Care. The operating and supporting partners of
      the RARE Campaign offered monthly webinars for sharing of best practices, and
      hosted Action Learning Days and celebratory events. Potentially preventable
      readmissions (PPRs) were tracked over time, and a ratio of actual-to-expected
      PPRs (A/E PPRs) was calculated for each hospital and reported quarterly. RESULTS:
      As of December 31, 2013, 82 hospitals were participating, with 58 (71%) taking
      part in at least one learning collaborative. More than 7,000 readmissions have
      been prevented, and patients have spent more than 28,000 nights of sleep in their
      own beds rather than in a hospital. By the end of September 2013, the A/E PPR
      ratio was reduced by 12%-from .98 to .86. CONCLUSIONS: The peer-to-peer
      networking and collaboration between hospitals facing similar issues, coupled
      with statewide resources, collaborating Operating Partners, and support for
      system improvements, have led to improved discharge planning, better management
      of care transitions and medications, engaged patients and families, and lower
      readmission rates.

PMID- 24919251
TI  - Patient safety first... a California partnership for health.
AB  - BACKGROUND: In California in 2009, Anthem Blue Cross joined forces with three
      regional hospital associations (RHAs) and an independent evaluator in an initial
      three-year, $6-million effort to address patient safety. METHODS: During Phase 1
      of the Patient Safety First... a California Partnership for Health program (2010
      2012), more than 180 of the 395 hospitals represented by the RHAs shared and
      implementated best practices in learning collaboratives. The three initial areas
      of focus were (1) health care-associated infections-ventilator-associated
      pneumonia (VAP), central line-associated bloodstream infection (CLABSI), and
      catheter-associated urinary tract infection (CAUTI); (2) sepsis mortality; and
      (3) perinatal care-reduction of elective deliveries prior to 39 weeks of
      gestation. To measure progress, the difference in the average rates from 2009
      (baseline) to 2012 was calculated using data from hospitals that reported for
      every quarter from 2009 through 2012. RESULTS: The rate decreases-57% for VAP
      cases per 1,000 ventilator-days, 43% for CLABSI cases per 1,000 central line
      days, 24% reduction for CAUTI cases per 1,000 patient-days, 26% reduction for
      sepsis deaths per 100 sepsis cases, and 74% for elective deliveries < 39
      gestational weeks-were statistically significant at the .05 level, except for
      CAUTI. A cost-avoidance analysis showed that these reductions were associated
      with a saving of 3,576 lives and an avoidance of $63.8 million in costs statewide
      (not limited to Anthem Blue Cross members). CONCLUSION: The Patient Safety First
      program provides a long-term opportunity for collaboration among different health
      care sectors to share best practices to improve health care for Californians.
      Phase 2 will continue to addresssepsis and elective deliveries and add other
      initiatives.

PMID- 24919252
TI  - The Vidant Health quality transformation.
AB  - BACKGROUND: Vidant Health (VH), a private, not-for-profit health system in
      eastern North Carolina, began a systemwide quality transformation in 2006 after a
      serious blood event resulted in a patient's death. METHODS: Systemwide patient
      safety training served as the foundation of the transformation. Strategic
      planning of the quality work outlined a series of approaches that included board
      literacy in quality, an aggressive transparency policy, patient-family
      partnerships, and leader and physician engagement. RESULTS: The transformation of
      the system has resulted in an 85% reduction in serious safety events, a 62%
      reduction in health care-associated infections, 98% optimal care in the Centers
      for Medicare & Medicaid Services (CMS)/Joint Commission core measures, Hospital
      Consumer Assessment of Healthcare Providers and Systems performance in the top
      20%, and more than 150 patient advisors partnering with leaders, physicians, and
      frontline staff. From the bedside to the boardroom the improvement in quality is
      evident across VH's nine hospitals, 70 physician practices, ambulatory surgery,
      and home health, hospice, and wellness services. CONCLUSION: Strategic planning
      for quality set an ambitious agenda for VH's quality work and continues to drive
      action today. Engaging patients in quality work at all levels--as partners on
      performance improvement teams, in safety rounds, in quality improvement committee
      meetings, and in the boardroom--has been a deliberate strategy and a significant
      part of the quality transformation at VH. Additional requirements for public
      reporting, CMS's new payment reform, and the challenges inherent in the evolving
      health care industry at large make it imperative to maintain a focus on zero
      events of harm and exceptional patient experiences.

PMID- 24919253
TI  - Development and sustainability of an inpatient-to-outpatient discharge handoff
      tool: a quality improvement project.
AB  - BACKGROUND: After hospital discharge, patients are at risk for medication errors,
      missed test results, adverse events, and readmissions. Handoff communication
      between the inpatient and outpatient settings is primarily accomplished with the
      discharge summary. However, critical information can often be missing, such as
      the date of the first postdischarge follow-up visit, a complete and accurate list
      of discharge medications, and follow-up recommendations. There have been no
      studies focusing on identifying and implementing a parsimonious, clinically
      relevant, inpatient-to-outpatient discharge handoff tool within a fully
      integrated electronic medical record (EMR) system. A concise, written, electronic
      handoff communication tool was created to address this gap. METHODS: Using
      inpatient and outpatient provider stakeholder input, a standard, succinct, and
      clinically relevant handoff tool was designed and implemented within the Veterans
      Affairs EMR. Retrospective chart review at 3 and 15 months after the handoff tool
      rollout in December 2010 was conducted to monitor handoff uptake and outcomes.
      RESULTS: At 15 months after implementation, 86% (129/150) of patients had a
      completed handoff at the time of discharge. More handoff notes were available in
      the EMR within 24 hours of discharge than discharge summaries (100% versus 77%, p
      < .0001). There was no difference between those patients with or without a
      handoff in the number of emergency department visits or readmissions. DISCUSSION:
      A standardized clinically relevant discharge handoff tool had high user uptake
      and sustainability and improved timeliness of communication of information
      between the hospital and outpatient setting. Even within a fully integrated EMR
      system, simple and efficient handoffs between inpatient and outpatient providers
      may fulfill a communication gap at the time of discharge.

PMID- 24919254
TI  - Using a triggered endocrinology service consultation to improve the evaluation,
      management, and follow-up of osteoporosis in hip-fracture patients.
AB  - BACKGROUND: Nearly 2 million osteoporosis-related fractures occur yearly in the
      United States, with more than 400,000 requiring hospital admissions. Fewer than
      30% receive proper evaluation and care for osteoporosis, representing a large
      opportunity to enhance secondary prevention of fractures. Methods to improve
      identification and triage of hospitalized fragility-fracture patients are
      desirable. METHODS: A multidisciplinary team was created, and definitions were
      established for an evidence-based best-practice protocol to assess, treat, and
      document an osteoporosis diagnosis and triage patients with hip-fragility
      fractures on the basis of the best-practice recommendations from The Joint
      Commission and the National Osteoporosis Foundation. The team initiated a
      preauthorized osteoporosis consultation from the endocrinology service for hip
      fracture patients, "triggered" via a brief query in admission orders or by the
      orthopedic service nurse practitioner. Osteoporosis consultations used a
      consultation template reflecting the protocol. RESULTS: Data were analyzed for 71
      baseline patients and 61 intervention patients. The groups possessed similar age,
      gender, race, and body mass index characteristics. The baseline (on-demand
      consultation) group suffered from poor performance, with only 3%-21% of patients
      receiving the desired evaluation, documentation, treatment, or outpatient follow
      up. Intervention (triggered-consultation) patients improved markedly
      postintervention, With performance increasing by 52%-76% on all parameters except
      outpatient follow-up, which changed insignificantly (6%-15%). CONCLUSION:
      Although triggered consultation was effective, multimodal layered interventions
      may achieve even better results and address several identified barriers.

PMID- 24919255
TI  - Surgical programs in the Veterans Health Administration maintain briefing and
      debriefing following medical team training.

PMID- 24919256
TI  - [Economic and logistical problems of radiation oncology].
AB  - An analysis of economic and logistical problems of radiation oncology is
      presented based on domestic and foreign literature. Despite the high efficacy of
      radiotherapy this branch of oncology is not financed enough in most countries. As
      a consequence, it is ubiquitously marked radiotherapy capacity deficit that does
      not allow to fully realize its therapeutic potential. Medical electron
      accelerators and related equipment have become increasingly complex and expensive
      and radiotherapy techniques more consuming. Even in developed countries growing
      waiting times for radiotherapy, not using the most modern and efficient
      radiotherapy technologies (image guiding, etc.) has become a daily reality. Based
      on these data, we assessed the prospects and possibilities of upgrading the
      technical base of radiation oncology in Russia including the development of
      hadron therapy.

PMID- 24919257
TI  - [Light-induced disruption of the circadian clock and risk of malignant tumors in
      laboratory animals: state of the problem].
AB  - There were obtained sufficient experimental evidence of the stimulating effect on
      the development of tumors (transplanted, spontaneous and induced by various
      carcinogenic agents), disorders of circadian function of the pineal gland (light
      induced desynchronosis) caused by knockout or mutation of clock genes,
      pinealectomy, content in conditions of constant light or natural light regime of
      the North, as well as jetlag modeling in laboratory rodents. In experiments on
      various models of carcinogenesis it was found that sympathectomy (removal of the
      superior cervical ganglion), light deprivation, hibernation and application of
      melatonin, the natural hormone of the pineal gland, had an inhibitory effect on
      the development of transplanted, spontaneous and induced tumors of different
      histogenesis.

PMID- 24919258
TI  - [Current state of the problem of treatment and prognosis of colorectal cancer].
AB  - The article presents an overview of the current state of the problem of
      colorectal cancer based on the features of its various clinical forms. It was
      shown that despite the fact that the surgical method was the leading cancer
      treatment for colon and rectum cancer the preference should be given to the
      combined and complex methods and in the treatment of squamous cell carcinoma of
      the anal canal, the emphasis was on conservative treatment with chemoradiation,
      leading to stable remission that avoided traumatic surgery in most cases. Also
      current data are presented on the necessity to identify circulating and
      disseminated tumor cells to refine prognosis and further explore ways to improve
      long-term results.

PMID- 24919259
TI  - [Survival of patients with malignant brain tumors in St. Petersburg and
      Arkhangelsk region].
AB  - The results of studies are presented of the dynamics on survival of patients with
      malignant tumors of the brain and other parts of central nervous system (C70-72)
      over a long period at the population level (St. Petersburg and Arkhangelsk
      region) by sex, age, histological structure and other parameters.

PMID- 24919260
TI  - [Clinical and morphological features of papillary thyroid cancer in children and
      adolescents in the Republic of Belarus: analysis of 936 post-Chernobyl
      carcinomas].
AB  - There is presented clinical and morphological characteristics of post-Chernobyl
      papillary thyroid cancer in 936 children and adolescents. In general, carcinoma
      of these patients featured by locally advanced growth - 57.4% (387 of 674
      patients with this sign could be assessed), metastases in regional lymph nodes -
      73,7% (N1b in 40.7%) and internal organs - 11.1%. The mean duration of follow-up
      was 12,4 +/- 3,5 years (range 4.3 to 19.6 years) including children 14,6 +/- 2,7
      years (range 8.8 to 19.6 years) and adolescents - 10,1 +/- 3,1 years (range 4.3
      to 18.8 years). Overall survival for the 20-year period was 96,6% +/- 1,2%. The
      causes of death were suicide (7), injuries and accidents (5), secondary
      malignancies (1), somatic diseases (2). Only in two patients the death was
      related to the main disease - lung metastases. Free-recurrence survival for the
      cohort of post-Chernobyl carcinomas was 92,7% +/- 1,0%.

PMID- 24919261
TI  - [Immunohistochemical examination of MSH2, PMS2, MLH1, MSH6 compared with the
      analysis of microsatellite instability in colon adenocarcinoma].
AB  - Adenocarcinoma of the colon in 10-20% is associated with microsatellite
      instability, which can occur both in sporadic cancers and in hereditary
      nonpolyposis colon cancer. Our analysis of 195 cases of adenocarcinoma of the
      colon showed that microsatellite instability (MSI-H) was found only in 1.5% of
      patients. Subsequent choice of patients with suspected hereditary Lynch syndrome
      led to the identification of additional 17 patients with microsatellite
      instability. They passed an analysis of genes of repair system of unpaired
      nucleotides of DNA. The study showed that immunohistochemical staining of MSH2,
      MSH6, MLH1, PMS2 could effectively conduct a preliminary screening of the Lynch
      syndrome but was unable to divide cases of sporadic and hereditary MSI-H colon
      cancer.

PMID- 24919262
TI  - [The use of SPECT-CT in the diagnosis of cancerous lesions of axillary lymph
      nodes in patients with breast cancer].
AB  - The purpose of the study was to explore the possibilities of a new hybrid
      technology of SPECT-CT in the diagnosis of metastatic regional lymph nodes (LN)
      in patients with breast cancer (BC). There were examined 57 primary patients. All
      patients underwent axillary lymph node dissection and /or biopsy of sentinel LN
      followed by histological examination of the material. Metastases in LN were
      verified in 20 (35%) of 57 examined patients. Sensitivity, specificity and
      overall accuracy of SPECT-CT in the combined use of anatomical and functional
      criteria for assessing the state of LN accounted for 75%, 89% and 84%,
      respectively. Sensitivity of SPECT-CT in the diagnosis of massive axillary LN
      lesion (more than two) in breast cancer patients was 95%. Thus, the new hybrid
      technology of SPECT-CT, combining functional and anatomical techniques for
      assessing of pathological changes, is highly informative in the diagnosis of
      metastatic lesions of regional LN in patients with breast cancer.

PMID- 24919263
TI  - [Prognostic value of the determination of bone marrow lesion in patients with
      neuroblastoma based on the gene PHOX2B and TH expression].
AB  - Bone marrow (BM) involvement in neuroblastoma patients is commonly detected by
      cytomorphology and associated with poor outcome. Molecular techniques, flow
      cytometry and immunocytochemistry were offered to detect low number of tumor
      cells in BM due to high value of analytical sensitivity, while prognostic
      significance of results, obtained with these methods is unclear. PHOX2B and/or TH
      genes expression was selected as molecular marker of BM involvement. It was
      determined in 411 BM samples obtained from 75 neuroblastoma patients. 263 BM
      samples were taken at the time of primary diagnosis, 80 during treatment and 68
      before autologous stem cells (ASC) apheresis. Prognostic significance of BM
      involvement was defined using 5-year (in some groups 4-year) overall (OS), event
      free (EFS) and progression free (PFS) survival. 24 patients (32.0%) were positive
      for PHOX2B and/or TH expression in the BM at the time of primary diagnosis. They
      had decreased survival rates: EFS achieved 0.49+/-0.12, OS - 0.57+/-0.12, PFS -
      0.54+/-0.12, comparing with 0.75+/-0.07, 0.80+/-0.07 and 0.77+/-0.07,
      respectively, in patients with negative BM, p=0.014, p=0.029 and p=0.033. The
      trend to decreased OS and PFS was detected in case of minimal residual disease
      presence at the end of the induction chemotherapy (OS and PFS both are 0.22+/
      0.19 vs. 0.70+/-0.18 and 0.43+/-0.22, correspondingly, p=0.121, p=0.130).
      Detection of PHOX2B and/or TH genes expression in the BM before ASC harvesting
      led to significant decreasing of EFS and OS (0.00 vs. 0.59+/-0.14 and 0.75+/
      0.13, respectively, p=0.021 and p=0.016).

PMID- 24919264
TI  - [Topoisomerase IIa expression in correlation with clinical and morphological
      parameters and proliferation (based on argyrophilic proteins of nucleolar
      organizer regions and Ki-67 antigen) in lung adenocarcinoma].
AB  - Investigated topoisomerase IIalpha (TopoII alpha), argyrophilic proteins
      associated with nucleolar organizer regions (Ag-NOR) and antigen Ki-67 in lung
      adenocarcinoma. Defined tumor with low and high TopoII alpha, Ag-NOR and Ki-67.
      TopoII alpha had a relationship with clinical and morphological parameters
      (greatest dimension, tumor differentiation) and proliferation markers (Ag-NOR, Ki
      67) . Survival of patients with lung adenocarcinoma with low content of TopoII
      alpha is better as compared with high content of TopoII alpha. Survival of
      patients with lung adenocarcinoma depends on the mutual content of TopoII alpha
      and clinical and morphological parameters (value T, greatest dimension, value N,
      stage, tumor differentiation), proliferation markers (Ag-NOR). TopoII alpha
      content in lung adenocarcinoma is an independent prognostic factor. Mutual
      research of TopoII alpha with clinical and morphological parameters and Ag-NOR
      has prognostic value in lung adenocarcinoma.

PMID- 24919265
TI  - [The reaction of the immune system to insulinlike growth factor-1 in
      postmenopausal women with breast cancer].
AB  - Taking into account the information about the role of insulin-like growth factor 
      1 (IGF-1) in breast cancer the main aim of the present study was to investigate
      the cellular immune response to IGF-1. There were examined 58 patients with
      breast cancer (61 +/- 1 years, BMI 31,2 +/- 0,9 kg/m2, all postmenopausal) and 10
      with benign tumors of the breast (56 +/- 2 years, BMI 30,8 +/- 0,7 kg/m2 all
      menopausal) as well as 17 patients suffering from cancer of different sites.
      Sensibilization of lymphocytes to IGF-1 was measured in the reaction of blast
      transformation of peripheral blood lymphocytes. The majority of breast cancer
      patients (47/58) revealed the sensibilization of peripheral blood lymphocytes to
      IGF-1. Thus in a part of patients (29 /47) this reaction was suppressed and
      revealed after suppression of cyclooxygenase and/or blocking of the histamine H2
      receptors by corresponding pharmaceutics drugs in vitro.

PMID- 24919266
TI  - [Antitumor effect of dioxadet in intraperitoneal chemoperfusion treatment for
      advanced ovarian cancer in experimental setting].
AB  - The study of antitumor efficacy of dioxadet in chemoperfusion treatment of
      ascitic ovarian cancer was carried out in 125 Wistar female rats. Ovarian cancer
      was inoculated intraperitoneally at a number 1x10(7) tumor cells per rat.
      Intraperitoneal administration of dioxadet as well as chemoperfusion was
      performed once in 48 hours after the ovarian cancer inoculation. Dioxadet was
      used at maximal tolerated doses which were 1.5 mg/kg for intraperitoneal
      administration, 30 mg/kg for normothermic intraperitoneal chemoperfusion (IPEC),
      and 15 mg/kg for hyperthermic intraperitoneal chemoperfusion (HIPEC). Antitumor
      effects of dioxadet were estimated in increase of median survival. In the control
      group, where animals didn't receive any treatment, the median survival was 9
      days. Increase of the median survival after intraperitoneal administration of
      dioxadet, IPEC and HIPEC with dioxadet was 211% (p=0,001), 244% (p=0,001) and
      444% (p=0,001), respectively, compared to the control group. Hence,
      intraperitoneal chemoperfusion with dioxadet (normo- or hyperthermic) is more
      effective compared to standard intraperitoneal administration of the drug. At
      HIPEC with dioxadet potentiating antitumor action of hyperthermia and dioxadet on
      the ovarian cancer growth was achieved.

PMID- 24919267
TI  - [Ultrastructural changes in endothelial cells of blood capillaries of the Walker
      256 carcinosarcoma while treated with melatonin].
AB  - In Wistar rats with transplanted Walker 256 carcinosarcoma a use of melatonin as
      monoagent causes changes in intracellular organization of endothelial cells:
      reduced volume density of mitochondria, granular cytoplasmic network,
      micropinocytic vesicles, reduced the number density of free and attached
      ribosomes, which leads to increased apoptosis of tumor cells of Walker 256
      carcinosarcoma.

PMID- 24919268
TI  - [Reasons of non-radical surgery for patients with primary skin melanoma].
AB  - It was found that up to now a significant number of patients with primary skin
      melanoma continued to have non-radical surgery. Based on the analysis of clinical
      and morphological data on 288 of these patients it was revealed that most non
      radical treatment was performed for patients who had had primary skin melanoma of
      linear dimensions of 1 cm and a pink color. It was proved that patients with
      tumors of the skin should first be examined by the oncologist. A lack of
      knowledge of semiotics of primary skin melanoma was revealed among doctors.
      Widely used diagnostic biopsy of the primary tumor with subsequent cytology is
      recommended.

PMID- 24919270
TI  - [Physician and medical psychologist: complementary approaches in providing
      psychological care to cancer patient].
AB  - In providing psychological care to an oncological patient a physician and a
      medical psychologist come from a variety of professional positions that require
      different approaches and methods. It is proposed a three-phase model of the
      dynamics of the psychological state of the person in the situation of cancer
      reflecting the process of psychological adaptation of a particular patient.
      Focusing on this model, the authors conclude that psychological care to cancer
      patient, performed by a doctor and a medical psychologist, are different kinds of
      psychological care that does not replace but complement each other.

PMID- 24919269
TI  - [Analysis of one-year mortality of radically operated patients over 70 years with
      nonsmall cell lung cancer].
AB  - One-year lethality was studied in 613 patients older than 70 years who underwent
      surgery for lung cancer for the period of 1970-2002. During the first year after
      surgery 166 patients died (27.1%) and besides from the generalization of the
      disease - 92.2%, from other causes - 7.8%. The highest rate of one-year lethality
      was observed after pneumonectomy (39.4%), the lowest one - after lung margins
      resection (16.5%). It was found that the most important factor in one-year
      lethality rate was N2 lymph node status. Risk of dying from the generalization of
      the disease during the first year sharply increased in group of patients
      underwent extended and combined pneumonectomy (one-year lethality of 52.6% and
      57.1%, respectively), pneumonectomy with N2 (56,0%), lobectomy in peripheral
      cancer with metastases of N2 level (63,6%), especially when the amount of the
      tumor was more than 5 cm (83.3%).

PMID- 24919271
TI  - [Institute of Oncology during the war and the siege of Leningrad].
AB  - There is described the activities of employees of the NN Petrov Institute of
      Oncology during the Great Patriotic War and the siege of Leningrad.

PMID- 24919273
TI  - [Slaughter on request: what motivates perpetrators and victims: "Thou shall not
      kill" (interview by Dr. Elke Oberhofer)].

PMID- 24919272
TI  - [Papular rash under the breasts: is it persistent zoster? Grover disease].

PMID- 24919274
TI  - [New KBV executive: family practitioners are not a Gassen fan club].

PMID- 24919275
TI  - [Prescribing blood glucose reagent strips: how do I protect my medication
      budget?].

PMID- 24919276
TI  - [New KBV executive. It must come through Gassen, the eternal peace].

PMID- 24919277
TI  - [Which drugs? Which diet? Treating your gout patient properly].

PMID- 24919278
TI  - [Suspected rheumatoid arthritis: which patient must be referred to a specialist?
      The family physician decides].

PMID- 24919279
TI  - [Subcutaneous infusion for dehydration: Is that not off-label use?].

PMID- 24919280
TI  - [Answer by Dr. med J. Zeeh, Meiningen].

PMID- 24919281
TI  - [Deaths from hives: from faulty injection technique?].

PMID- 24919282
TI  - [Answer by Dr. C. Grove, Munich].

PMID- 24919283
TI  - [Patient throws money out the window: the unusual diagnoses of the osteopath].

PMID- 24919284
TI  - [The cognitively impaired patient suddenly became disoriented: dementia is not
      responsible].

PMID- 24919285
TI  - [How long is it then actually?].

PMID- 24919286
TI  - [The stethoscope as pathogen transmitter].

PMID- 24919287
TI  - [Does acupuncture reduce stroke risk after craniocerebral trauma?].

PMID- 24919288
TI  - [Lung function in mucoviscidosis: which marker is the most telling?].

PMID- 24919289
TI  - [Aggressive pacemaker].

PMID- 24919290
TI  - [Is the Frank sign an accurate predictor?].

PMID- 24919291
TI  - [Smoking cessation helps body and soul].

PMID- 24919292
TI  - [Coronary arteriosclerosis between good and evil].

PMID- 24919293
TI  - [Medical therapy of coronary artery disease].

PMID- 24919294
TI  - [Advances in the management of patients with acute myocardial infarction].

PMID- 24919295
TI  - [Sexuality counselling for adolescents].

PMID- 24919296
TI  - [Otorrhea].

PMID- 24919297
TI  - [The right to live and the right to die].

PMID- 24919298
TI  - [Music therapy against hypertension].

PMID- 24919299
TI  - Pay-for-performance: toxic to quality? Insights from behavioral economics.
AB  - Pay-for-performance programs aim to upgrade health care quality by tailoring
      financial incentives for desirable behaviors. While Medicare and many private
      insurers are charging ahead with pay-for-performance, researchers have been
      unable to show that it benefits patients. Findings from the new field of
      behavioral economics challenge the traditional economic view that monetary reward
      either is the only motivator or is simply additive to intrinsic motivators such
      as purpose or altruism. Studies have shown that monetary rewards can undermine
      motivation and worsen performance on cognitively complex and intrinsically
      rewarding work, suggesting that pay-for-performance may backfire.

PMID- 24919300
TI  - The widening U.S. health care crisis three years after the passage of
      'Obamacare'.
AB  - This report presents information on the state of the U.S. health system in 2012
      and early 2013, specifically the period prior to the implementation of the
      individual mandate and full rollout of the Affordable Care Act's online health
      exchanges. The authors include data on the uninsured and underinsured and their
      access to health care, on socioeconomic inequality in health care, the rising
      costs of the U.S. health system, and the role of corporate money in health care,
      with special reference to the pharmaceutical industry. They also provide updates
      on Medicare health maintenance organizations, Medicaid, and a prelude to the
      complete implementation of the Affordable Care Act. In addition, the authors
      include some results from public opinion polls on health systems and
      international system comparisons. The article concludes with an assessment of the
      rapid consolidation in the delivery of health care being driven by the Affordable
      Care Act.

PMID- 24919301
TI  - Family policy and inequalities in health in different welfare states.
AB  - This article focuses on differences in health and welfare outcomes for families
      with children in three European countries, discussed in relation to national
      policies for child and family welfare. Data consist of policy documents and cross
      national surveys. The document analysis was based on policy documents that
      described government policies. The statistical analyses utilize data from the
      European Social Survey. For the analyses in this article, a sub-sample of child
      families was selected from the countries Slovenia, Sweden, and the United
      Kingdom. Data showed that England's policy has mainly addressed socially
      disadvantaged groups and areas. Sweden and Slovenia are mainly developing
      universal policies. The United Kingdom has high scores for subjective general
      health, but a steep income gradient in the population. Parents in England
      experience the highest level of at-risk-of-poverty. Sweden generally scores well
      on health outcomes and on level of at-risk-of-poverty, and the gradient in self
      rated general health is the mildest. Slovenia has the weakest economy, but low
      levels of inequality and low child at-risk-for-poverty scores. The Slovenian
      example suggests that not only the level of economic wealth, but also its
      distribution in the population, has bearings on health and life satisfaction, not
      least on the health of children.

PMID- 24919302
TI  - Is the swiss health care system a model for the United States?
AB  - Both supporters and critics of the Patient Protection and Affordable Care Act
      (ACA) have argued that it is similar to Switzerland's Federal Law on Health
      Insurance (LAMal), which currently governs Swiss health care, and have either
      praised or condemned the ACA on the basis of this alleged similarity. I challenge
      these observers on the grounds that they overlook critical problems with the
      Swiss model, such as its inequities in access, and critical differences between
      it and the ACA, such as the roots in, and continuing commitment to, social
      insurance of the Swiss model. Indeed, the daunting challenge of attempting to
      impose the tightly regulated model of operation of the Swiss model on mega
      corporations like UnitedHealth, WellPoint, or Aetna is likely to trigger no less
      ferocious resistance than a fully public, single-payer system would. I also
      conclude that the ACA might unravel in ways unintended or even opposed by its
      designers and supporters, as employers, confronted with ever-rising costs,
      retreat from sponsoring insurance, and workers react in outrage as they confront
      the unaffordable underinsurance mandated by the ACA. A new political and
      ideological landscape may then ensue that finally ushers in a truly national
      health program.

PMID- 24919303
TI  - The fallacies in arguing that current high unemployment in Spain (27%) is a
      consequence of supposed labor market rigidities.
AB  - This article refutes the argument that high unemployment in Spain is due to labor
      market rigidities, questioning the premises on which this theory is based. It
      then goes on to explain how those advancing this argument are the very same
      forces responsible for the macroeconomic decisions that are currently causing
      unemployment.

PMID- 24919304
TI  - To live and die in America: labor in the time of cholera and cancer.
AB  - A popular explanation of the epidemiological transition is that the germs that
      caused infectious disease mortality were defeated by the "magic bullets" of
      mainstream medicine over the course of the 20th century, permitting the
      population to get old enough to get the chronic diseases of heart disease and
      cancer. This explanation is false. The most important causes of infectious
      disease were the political and economic structures that favored capital at the
      expense of labor so blatantly that it left a large portion of the working
      population virtually at death's door. This was remedied only when resistance by
      labor created a more livable workday, child labor laws, and a higher wage,
      resulting in improvements in nutrition and housing. Chronic disease increased as
      firms transformed the production process by introducing more mechanized and
      chemically intensive production processes. This has transformed our food, water,
      air, and work processes in unprecedented ways and created a historically unique
      chronic disease pattern.

PMID- 24919305
TI  - All part of the job? The contribution of the psychosocial and physical work
      environment to health inequalities in Europe and the European health divide.
AB  - This study is the first to examine the contribution of both psychosocial and
      physical risk factors to occupational inequalities in self-assessed health in
      Europe. Data from 27 countries were obtained from the 2010 European Working
      Conditions Survey for men and women aged 16 to 60 (n = 21,803). Multilevel
      logistic regression analyses (random intercept) were applied, estimating odds
      ratios of reporting less than good health. Analyses indicate that physical
      working conditions account for a substantial proportion of occupational
      inequalities in health in both Central/Eastern and Western Europe. Physical,
      rather than psychosocial, working conditions seem to have the largest effect on
      self-assessed health in manual classes. For example, controlling for physical
      working conditions reduced the inequalities in the prevalence of"less than good
      health" between the lowest (semi- and unskilled manual workers) and highest
      (higher controllers) occupational groups in Europe by almost 50 percent (Odds
      Ratio 1.87, 95% Confidence Interval 1.62-2.16 to 1.42, 1.23-1.65). Physical
      working conditions contribute substantially to health inequalities across "post
      industrial" Europe, with women in manual occupations being particularly
      vulnerable, especially those living in Central/Eastern Europe. An increased
      political and academic focus on physical working conditions is needed to explain
      and potentially reduce occupational inequalities in health.

PMID- 24919307
TI  - The role of international NGOs in health systems strengthening: the case of Timor
      Leste.
AB  - Achieving the United Nations Millennium Development Goals for health will require
      that programs supporting health in developing countries focus on strengthening
      national health care systems. However, the dominant neoliberal model of
      development mandates reduced public spending on health and other social services,
      often resulting in increased funding for nongovernmental organizations (NGOs) at
      the expense of support for government systems. East Timor, later Timor-Leste, is
      an example of a post-crisis country where international NGO efforts were
      initially critical to providing relief efforts to a traumatized population. Those
      groups were not prepared to help develop and support a standardized Timorese
      national health plan, however, and the cost of their support was unsustainable in
      the long term. In response, local authorities designed and implemented a post
      crisis NGO phase-over plan that addressed risks to service disruption and
      monitored the process. Since then, some NGOs have worked collaboratively with the
      Ministry of Health to support specific efforts and initiatives under a framework
      provided by the ministry. Timor-Leste has shown that ministries of health can
      facilitate an effective transition of NGO support from crisis to development if
      they are allowed to plan and manage the process.

PMID- 24919306
TI  - Big pharma and the problem of disease inflation.
AB  - Over the course of the past decade, critics have increasingly called attention to
      the corrosive influence of the pharmaceutical industry on both biomedical
      research and the practice of medicine. Critics describe the industry's use of
      ghostwriting and other unethical techniques to expand their markets as evidence
      that medical science is all-too-frequently subordinated to the goals of corporate
      profit. While we do not dispute this perspective, we argue that it is imperative
      to also recognize that the goals of medical science and industry profit are now
      tightly wed to one another. As a result, medical science now operates to expand
      disease definitions, lower diagnostic thresholds, and otherwise advance the goals
      of corporate profit through the redefinition and expansion of what it means to be
      ill. We suggest that this process has led to a variety of ethical problems that
      are not fully captured by current critiques of ghostwriting and other troubling
      practices by the pharmaceutical industry. In our conclusion, we call for
      physicians, ethicists, and other concerned observers to embrace a more
      fundamental critique of the relationship between biomedical science and corporate
      profit.

PMID- 24919308
TI  - Management commitments and primary care: another lesson from Costa Rica for the
      world?
AB  - Maintained dedication to primary care has fostered a public health delivery
      system with exceptional outcomes in Costa Rica. For more than a decade,
      management commitments have been part of Costa Rican health reform. We assessed
      the effect of the Costa Rican management commitments on access and quality of
      care and on compliance with their intended objectives. We constructed seven
      hypotheses on opinions of primary care providers. Through a mixed qualitative and
      quantitative approach, we tested these hypotheses and interpreted the research
      findings. Management commitments consume an excessive proportion of consultation
      time, inflate recordkeeping, reduce comprehensiveness in primary care
      consultations, and induce a disproportionate consumption of hospital emergency
      services. Their formulation relies on norms in need of optimization, their
      control on unreliable sources. They also affect professionalism. In Costa Rica,
      management commitments negatively affect access and quality of care and pose a
      threat to the public service delivery system. The failures of this pay-for
      performance-like initiative in an otherwise well-performing health system cast
      doubts on the appropriateness of pay-for-performance for health systems
      strengthening in less advanced environments.

PMID- 24919309
TI  - Beyond accreditation: a multi-track quality-enhancing strategy for primary health
      care in low- and middle-income countries.
AB  - Many define an equitable health care system as one that provides logistical and
      financial access to "quality" care to the population. Realizing that fact, many
      low- and middle-income countries started investing in enhancing the quality of
      care in their health care systems, recently in primary health care.
      Unfortunately, in many instance, these investments have been exclusively focused
      on accreditation due to available guidelines and existing accrediting structures.
      A multi-track quality-enhancing strategy (MTQES) is proposed that includes, in
      addition to promoting resource-sensitive accreditation, other quality initiatives
      such as clinical guidelines, performance indicators, benchmarking activities,
      annual quality-enhancing projects, and annual quality summit/meeting. These
      complementary approaches are presented to synergistically enhance a continuous
      quality improvement culture in the primary health care sector, taking into
      consideration limited resources available, especially in low- and middle-income
      countries. In addition, an implementation framework depicting MTQES in three
      phase interlinked packages is presented; each matches existing resources and
      quality infrastructure. Health care policymakers and managers need to think about
      accreditation as a beginning rather than an end to their quest for quality.
      Improvements in the structure of a health delivery organization or in the
      processes of care have little value if they do not translate to reduced
      disparities in access to "quality" care, and not merely access to care.

PMID- 24919310
TI  - When constitutional justice has the last word on health care: the case of Chile.
AB  - The Chilean health care system is in crisis. Since the recent ruling of the
      Constitutional Court that declared the risk rating (actuarial insurance) of
      private health insurers unconstitutional, all of the social actors related to
      health care have tried to agree on a legislative reform that would overcome the
      existing highly segmented and inequitable system, which is a legacy of Pinochet's
      dictatorship. Here we demonstrate how the social and political demands for
      legislative reform in the health care sector have been supported by the decisions
      of the courts. To achieve its goals of reducing equity gaps in health and ending
      the judicialization of health care (claims for protection represent almost 70% of
      total resources of the courts), the National Congress of Chile is trying to
      create a new national health insurance system that guarantees the right to a
      minimum level of health care. Part of this effort involves obtaining the
      constitutional approval of the courts. In Chile, justice has the final word on
      health care.

PMID- 24919311
TI  - Community-oriented primary care (COPC) in Barcelona, Spain: an urban COPC
      experience.
AB  - Community-oriented primary care (COPC) integrates comprehensive primary care with
      community health. Although it has had limited application in the United States,
      this model has been widely promoted among urban family physicians in Barcelona,
      Spain. This article describes the current status of COPC in four community
      clinics in Barcelona. Data were derived from a site visit that included direct
      observation and interviews with professionals involved in community health. The
      interviews explored how COPC has been implemented in each of the four primary
      care centers. We found that the degree to which COPC is practiced is quite varied
      and that it often coexists with other community health programs. A number of
      obstacles, including lack of support and funding from the government and lack of
      motivation and participation among health professionals, make practicing COPC in
      Barcelona a challenge. Despite these obstacles, COPC is flourishing in Barcelona.
      This experience may offer guidance for COPC implementation in the United States
      and other countries.

PMID- 24919312
TI  - The secret to getting your foot in the door: the academic job search portfolio.

PMID- 24919313
TI  - President Obama releases FY 2015 budget proposal.

PMID- 24919314
TI  - APS comments on travel restrictions for federal scientists.

PMID- 24919315
TI  - [Within reason].

PMID- 24919316
TI  - [Less medicine, more common sense].

PMID- 24919317
TI  - ["Our goal is the awareness of the public"].

PMID- 24919318
TI  - [Ask your pharmacist about risks].

PMID- 24919319
TI  - [When coffee works wonders in wound management].

PMID- 24919320
TI  - [Feeling disgust in nursing care].

PMID- 24919321
TI  - [Support for remaining in the home environment].

PMID- 24919322
TI  - [4 blind dates of a special kind].

PMID- 24919323
TI  - [Launch of the continuing education program].

PMID- 24919324
TI  - ["For greater visibility and respect for nursing in Togo" (interview by Francoise
      Taillens)].

PMID- 24919325
TI  - [Meaningful work promotes good health].

PMID- 24919326
TI  - [No chance for misinterpretation].

PMID- 24919327
TI  - [Alcohol drinking in the hospital - (not) a problem].

PMID- 24919328
TI  - [Mathuselah complex].

PMID- 24919329
TI  - ["Reunited by a common passion: our future profession"].

PMID- 24919330
TI  - [Early rehabilitation to maximize the chances of recovery].

PMID- 24919331
TI  - [Jewish and Arab students under the same roof].

PMID- 24919332
TI  - [Smart phones at the bow, health liability].

PMID- 24919333
TI  - [Doing more does not mean better].

PMID- 24919334
TI  - ["The ultimate goal is to make consumers active participants"].

PMID- 24919335
TI  - [110 years--University Obstetrics and Gynecology Hospital "Maichin dom"].
AB  - The first specialized Obstetrics and Gynecology Hospital in Bulgaria was founded
      based on the idea of Queen Maria Luisa (1883). Construction began in 1896 and the
      official opening of the hospital took place on November 19, 1903. What is unique
      about the University Obstetrics and Gynecology Hospital "Maichin dom" is above
      all the fact that the Bulgarian school of obstetrics and gynecology was founded
      within its institution. Currently, the hospital has nearly 400 beds and 600
      employees who work at nine clinics and six laboratories, covering the entire
      spectrum of obstetric and gynecological activities. Its leading specialists still
      continue to embody the highest level of professionalism and dedication. The
      future development of the hospital is chiefly associated with the renovation of
      facilities, resources and equipment and with the enhancement of the professional
      competence of the staff and of the quality of hospital products to improve the
      health and satisfaction of the patients.

PMID- 24919336
TI  - [The insulin-like growth factor IGFBP-1--specific marker for preterm delivery in
      pregnant women with clinical symptoms].
AB  - The insulin-like growth factor IGFBP-1 is a binding protein (IBP-1), also known
      as placental protein (PP12), is encoded in people as IGFBP-1 gene. This gene
      encodes a protein in the domain of IGFBP-1 and domain thyroglobulin. During the
      last years highly phos-phorylated versions of IGFBP-1 (IGFBP-1 pM) have been
      found in decidual cells--a marker of threat for preterm birth. The quantity
      analysis of the insulin-like growth factor in the serum or heparinized plasma is
      used to locate diseases related to growth. Its levels in the plasma can scarcely
      be determined after birth and steadily rise with age while they reach their
      maximum during puberty. These levels rise constantly during pregnancy.

PMID- 24919337
TI  - [A weak association of 677 C>T polymorphism in MTHFR with recurrent embryonic
      loss].
AB  - Early (embryonic) pregnancy loss before 10 week of gestation (wg) could also be
      related with endometrial receptivity as well as with gene expression regulation
      in developed embryo. Methylation of genome is a key process in the gene
      expression. Because the methylenetetrahydrofolate reductase (MTHFR) have had
      significant role in methionine metabolism polymorphisms into the gene could be
      related with early embryonic development. This study evaluated relationship
      between T allele in 677 C>T polymorphism in MTHFR and recurrent embryonic loss
      development. One hundred six women with tree or more pregnancy loss before 10 wg
      and 165 women without reproductive failure have been evaluated for 677 C>T
      carrier status. Sixteen (15.1%) of women with pregnancy loss have had TT genotype
      and 54 (50.9%) are heterozygous carriers for T allele. T allele frequency was
      higher but not significant differ from carrier status in control group (13.9% for
      TT genotype and 43.9% for CT OR and 95% CI respectively 1.1, 0.52-2.3 u 1.34, 0.8
      2.26, p > 0.05). T allele (in homozygous and heterozygous carriers) was in higher
      but not significant prevalence in patients compared with controls (66% and 57.6%
      respectively, OR 1.43, 95% CI 0.84-2.46, p > 0.05), This study found a weak
      association between T allele carrier status (both in homozygous and heterozygous
      state) and recurrent embryonic loss development. T allele in 677 C>T polymorphism
      could be considered like an agent for early pregnancy wastage only in a
      constellation with other risk factors influencing embryonic development.

PMID- 24919338
TI  - [Pregnancy and delivery in women above the age of 35].
AB  - During the past decades there is a tendency among women in developed countries
      for postponing their reproductive plans for later age. This results from the
      substantial change of women's role in society and the development and
      availability of assisted reproduction technologies. The latter made possible
      women to become pregnant after the end of their reproductive years. In the
      present review, data from the literature, published in the recent 15 years and
      related to pregnancy course and outcome in women above the age of 35, are
      analyzed. Decreased fertility, higher incidence of early pregnancy complications
      including spontaneous abortions and ectopic pregnancy, and of congenital
      anomalies (chromosomal, structural, genetic syndromes) are discussed. Advanced
      maternal age is characterized with more frequent late pregnancy complication such
      as hypertension and diabetes. Problems of placentation, perinatal and maternal
      mortality are more frequent in these patients.. Data at present suggest higher
      risk for maternal and fetal pregnancy complications as maternal age advances. On
      the other hand, some positive aspects of postponing pregnancy have to be
      considered--financial, emotional, and the overall low absolute number of
      complications. With adequate antenatal care it is possible for women of advanced
      maternal age to have successful pregnancies with overall favorable outcome
      comparable to that in young women.

PMID- 24919339
TI  - [Three- and four-dimensional (3D/4D) ultrasound in obstetric practice: review].
AB  - Three-dimensional (3D) ultrasound is following the natural development of the
      imaging technology. This review of the technical applications and clinical
      aspects of the three-dimensional ultrasound is focused on vizualiztion of the
      fetal anatomy and the possibilities of this new technology and to increase
      awareness of its present clinical usefulness. Consulting specialists understand
      fetal pathology better and can better plan postnatal interventions. 3D ultrasound
      is a promising imaging method to image the fetus. Here are presented the methods
      for visualization in obstetrics, and the place of the ultrasound imaging in
      prenatal diagnosis. The role and value of this method will be in the focus of
      further studies.

PMID- 24919340
TI  - [Lichen sclerosus--clinical and therapeutic aspects].
AB  - Lichen sclerosus (LS) is a lymphocyte-mediated inflammatory dermatosis with a
      characteristic location (85-98%) in the anogenital region. The authors point out
      the main features in the epidemiology and clinical presentation of the disease
      and the possible approach to neoplastic development. Expanded differential
      diagnosis of LS sparked not only dermatologists but also gynecologists,
      urologists and GPs. Points are the chronic course of the disease and resistance
      to therapy. Discuss the results of the treatment of LS with less potent topical
      corticosteroids, calcineurin inhibitors, phototherapy and photodynamic therapy,
      surgery.

PMID- 24919341
TI  - [Sildenafil--for treatment of preeclampsia and intrauterine growth restriction].
AB  - Pre-eclampsia and intrauterine growth restriction (IUGR) are responsible for
      approximately 15-20% of serious maternal and neonatal diseases. These
      complications are related to very early anomalies of the uteroplacental
      circulation, accompanied, at least secondarily, by thromboxane-prostacyclin
      related imbalances. Studies have failed to show a beneficial effect of
      betamimetics and calcium channel blockers for the treatment of IUGR. Sildenafil
      citrate, a type 5-specific phosphodiesterase inhibitor, augments the vasodilatory
      effects of NO by preventing the degradation of cGMP There is a selective effect
      of Sildenafil on the uteroplacental circulation. Sildenafil improves uterine
      artery blood flow.

PMID- 24919342
TI  - [Public health ethics and reproduction].
AB  - Medical progress has enabled achievements that were not even thinkable earlier
      but at the same time society and public health have had to face new challenges.
      What are we ready to accept in the area of human reproduction? This paper aims at
      ethical analysis of Bulgarian laws on reproduction. The abortion debate nowadays
      has got new dimiension focusing not that much on its moral acceptability but
      rather on the acceptable indications for its performance. Is it ethical to
      perform abortion in case of undesired gender of the embryo or genetic
      malformations? Lots of moral issues mark the area of assisted reproduction which
      is due to the separation of the reproductive functions (ova, sperm and embryo
      donation, surrogacy), fragmentation of motherhood and fatherhood, differentiation
      of biological and social parenthood. Defining limits of acceptable interference
      or non-interference in human reproduction will never be easy, but dynamics of
      moral judgment shouldn't bother us. The rigidity of moral norms is what should be
      alarming because it threatens procreative autonomy.

PMID- 24919343
TI  - [Intrauterine fetal death in furcate insertion of umbilical cord].
AB  - Fatal complications associated with abnormal umbilical cord insertions occupy 7.7
      11.4% of all stillbirths and only 0.06% of all pregnancies. We report a rare
      abnormality of umbilical cord insertions (furcated insertion) associated with
      hemodynamic disorders and intrauterine death of the fetus.

PMID- 24919344
TI  - [Pregnancy and vaccinoprevention].
AB  - Vaccinations protect woman and her fetus against different infectious diseases,
      but their application on pregnant should be extremely responsible. In this review
      I present information about some infectious diseases and vaccines during
      pregnancy. Women, planning to get pregnant should be advised to do serological
      tests in order to find out their immune status against some infections, leading
      to fetal congenital malformations (rubella, chicken pox, hepatitis B) and if
      necessary to get vaccinated at least a month before pregnancy. Despite the lack
      of vaccines against Cytomegalovirus (CMV), parvovirus 19 and Toxoplasma gondii it
      is good to know woman's immune status against these infections in order to
      clarify the clinical approach in case of future contact with sick or carriers.
      Parvovirus 19 could cause fetal death, while CMV could be transmitted to the
      child. Immune women wouldn't get sick and wouldn't transmit Toxoplasmagondii to
      the fetus during pregnancy. Recommended vaccines before pregnancy include
      vaccines against flu, human papilloma virus, MMR (morbilli, measles, rubella),
      Tdap (tetanus, diphtheria, whooping cough), chicken pox. CDC-Atlanta recommends
      during pregnancy two vaccines--against flu, in case it wasn't done before
      pregnancy, and Tdap during every pregnancy between 27-th and 36-th gestation
      week. Whooping cough is very dangerous for the baby during the first two months
      after birth, while it is not yet vaccinated. From this point of view it is of
      best interest of the mother to have strong immunity in order to transfer
      antibodies during breastfeeding, as well as for the father and the rest who will
      take care for the newborn child to be vaccinated against whooping cough. During
      pregnancy vaccinations against tuberculosis, morbilli, measles, rubella,
      meningococcal disease, typhoid fever and chicken pox are contraindicated. In case
      of contact vaccinations against rabies, anthrax, small pox, poliomyelitis and
      yellow fever should be taken into consideration. Immediately after birth, if the
      vaccination against whooping cough is missed young mother vaccination is
      recommended. The vaccination is one of the greatest achievements of the modern
      medicine, but it is still an object of vigorous attacks, concerning used products
      safety. One of the most spreading fears is about sterility after vaccination.
      Over a period of three years (2009-2012) 563 women were vaccinated by SACMEH
      against HPV. Forty two of them (13.40%) interrupt vaccination due to pregnancy
      (18 of them after the first shot and 24 after the second shot). Our observations
      show, that this vaccine is carried out good by the patients, tit is safe and does
      not cause sterility.

PMID- 24919345
TI  - [Laparoscopic burch colposuspensio--our experience].
AB  - Stress incontinence is involuntary loss of urine that occurs during periods of
      increased intraabdominal pressure, such as sneezing, coughing or exercise.
      Retropubic Burch colposuspension has been considered by many to be the "gold
      standard" procedure for treatment of female stress urinary incontinence for
      almost 50 years. The firs reported retropubic surgery performed via the
      laparoscopic approach was described by Vancaillie and Schuessler in 1991. We
      present a clinical case of a female patient with stress incontinence who has been
      operated by laparoscopic approach by our team.

PMID- 24919346
TI  - Is the mind in the head? A belated response to Koenderink (1999).

PMID- 24919347
TI  - Pattern dot quantity affects auditory facilitation effects on visual object
      representations.
AB  - Auditory stimuli often facilitate visual perception. Audiovisual integration
      requires spatial and/or temporal proximity between visual and auditory stimuli;
      additionally, sensory processing speed affects the audiovisual integration
      process. In the present study we examined the relationship between processing
      speed and the auditory facilitation effect on visual representations by
      manipulating dot quantity patterns. We hypothesized that the auditory
      facilitation effect would be observed in longer interstimulus interval conditions
      with more dot quantities. This is because more processing time would be required
      to integrate visual and auditory stimuli. During a backward masking paradigm used
      in experiment 1, the auditory facilitation effect depended on dot quantity among
      patterns and the interval between visual stimuli and masks. Moreover, differences
      in processing time required to integrate visual and auditory stimuli between dot
      quantities was confirmed from a same-different discrimination task in experiment
      2. Therefore, dot quantity affects sensory processing time, and a longer
      processing time is required for integrating visual and auditory stimuli when
      visual dot quantity is high.

PMID- 24919348
TI  - Pointing to azimuths and elevations of targets: blind and blindfolded-sighted.
AB  - Three groups of observers pointed to target circles in a path on the ground, in
      two parallel rows. Participants in one group viewed the circles and then pointed
      blindfolded. Those in a second group were blindfolded and then touched the
      circles with a stick while walking past them. Volunteers in the third group were
      blind adults, a diverse group, who also used a stick to detect the circles. For
      all three groups, as distance to the circles increased, pointing azimuths shrank
      and elevations increased. We suggest that directions to targets on major
      environmental surfaces may be appreciated similarly by the blind and sighted. We
      challenge the assumption that the principle of convergence to the horizon,
      available through vision because of the way in which visual angle decreases on
      the retina, is not available through touch.

PMID- 24919349
TI  - Changes in context and perception of maximum reaching height.
AB  - Successfully performing a given behavior requires flexibility in both perception
      and behavior. In particular, doing so requires perceiving whether that behavior
      is possible across the variety of contexts in which it might be performed. Three
      experiments investigated how (changes in) context (ie point of observation and
      intended reaching task) influenced perception of maximum reaching height. The
      results of experiment 1 showed that perceived maximum reaching height more
      closely reflected actual reaching ability when perceivers occupied a point of
      observation that was compatible with that required for the reaching task. The
      results of experiments 2 and 3 showed that practice perceiving maximum reaching
      height from a given point of observation improved perception of maximum reaching
      height from a different point of observation, regardless of whether such practice
      occurred at a compatible or incompatible point of observation. In general, such
      findings show bounded flexibility in perception of affordances and are thus
      consistent with a description of perceptual systems as smart perceptual devices.

PMID- 24919350
TI  - Action-specific effects in aviation: what determines judged runway size?
AB  - Several recent studies have shown that the performance of a skill that involves
      acting on a goal object can influence one's judgment of the size of that object.
      The present study investigated this effect in an aviation context. Novice pilots
      were asked to perform a series of visual approach and landing manoeuvres in a
      flight simulator. After each landing, participants next performed a task in which
      runway size was judged for different simulated altitudes. Gaze behaviour and
      control stick kinematics were also analyzed. There were significant relationships
      between judged runway size and multiple action-related variables including
      touchdown velocity, time fixating the runway, and the magnitude and frequency of
      control inputs. These findings suggest that relationship between the perception
      of a target object and action is not solely determined by performance success or
      failure but rather involves a relationship between multiple variables that
      reflect the actor's ability.

PMID- 24919351
TI  - The effect of stimulus size on stereoscopic fusion limits and response criteria.
AB  - The stereoscopic fusion limit denotes the largest binocular disparity for which a
      single fused image is perceived. Several criteria can be employed when judging
      whether or not a stereoscopic display is fused, and this may be a factor
      contributing to a discrepancy in the literature. Schor, Wood, and Ogawa (1984
      Vision Research, 24, 661-665) reported that fusion limits did not change as a
      function of bar width, while Roumes, Plantier, Menu, and Thorpe (1997 Human
      Factors, 39, 359-373) reported higher fusion limits for larger stimuli than for
      smaller stimuli. Our investigation suggests that differing criteria between the
      studies could contribute to this discrepancy. In experiment 1 we measured
      horizontal and vertical disparity fusion limits for thin bars and for the edge of
      an extended surface, allowing observers to use the criterion of either diplopia
      or rivalry when evaluating fusion for all stimuli. Fusion limits were equal for
      thin bars and extended surfaces in both horizontal and vertical disparity
      conditions. We next measured fusion limits for a range of bar widths and
      instructed observers to indicate which criterion they employed on each trial.
      Fusion limits were constant across all stimulus widths. However, there was a
      sharp change in criterion from diplopia to rivalry when the angular extent of the
      bar width exceeded about twice the fusion limit, expressed in angular terms. We
      conclude that stereoscopic fusion limits do not depend on stimulus size in this
      context, but the criterion for fusion does. Therefore, the criterion for fusion
      should be clearly defined in any study measuring stereoscopic fusion limits.

PMID- 24919352
TI  - A norming study and library of 203 dance movements.
AB  - Dance stimuli have been used in experimental studies of (i) how movement is
      processed in the brain; (ii) how affect is perceived from bodily movement; and
      (iii) how dance can be a source of aesthetic experience. However, stimulus
      materials across--and even within--these three domains of research have varied
      considerably. Thus, integrative conclusions remain elusive. Moreover, concerns
      have been raised that the movements selected for such stimuli are qualitatively
      too different from the actual art form dance, potentially introducing noise in
      the data. We propose a library of dance stimuli which responds to the stimuli
      requirements and design criteria of these three areas of research, while at the
      same time respecting a dance art-historical perspective, offering greater
      ecological validity as compared with previous dance stimulus sets. The stimuli
      are 5-6 s long video clips, selected from genuine ballet performances. Following
      a number of coding experiments, the resulting stimulus library comprises 203
      ballet dance stimuli coded in (i) 25 qualitative and quantitative movement
      variables; (ii) affective valence and arousal; and (iii) the aesthetic qualities
      beauty, liking, and interest. An Excel spreadsheet with these data points
      accompanies this manuscript, and the stimuli can be obtained from the authors
      upon request.

PMID- 24919353
TI  - Reversing the reversed contrast.
AB  - Galmonte and Agostini (1998 Investigative Ophthalmology & Visual Science, 39(4),
      S158), Agostini and Galmonte (2002 Psychological Science, 13, 89-93), Bressan
      (2001 Perception, 30, 1031-1046), and Gilchrist and Annan (2002 Perception, 31,
      141-150) reported three different lightness contrast configurations in which
      grouping factors make a gray target totally surrounded by black appear darker
      than an equal gray target surrounded by white, reversing the classical contrast
      effect. In this paper we demonstrate that the three configurations known as
      'reversed contrast' are based on different mechanisms. Sixteen participants
      judged the lightness of the gray targets of the original and modified versions of
      the three configurations. Our results highlight that the Agostini and Galmonte
      effect is reversed when the global grouping factors are removed, while in a
      number of variations of Bressan's and Gilchrist and Annan's displays the
      direction of the effect does not change, even in absence of global grouping
      factors. Our results indicate that the factors determining the Agostini and
      Galmonte effect are different from those acting on the other two configurations,
      in which the lightness change is also due to factors other than belongingness.

PMID- 24919354
TI  - Evaluating training methods for facial image comparison: the face shape strategy
      does not work.
AB  - Human performance on unfamiliar face matching is known to be highly error prone.
      However, in organisations where staff are required to perform this task as part
      of their daily work, attempts are often made to mitigate risk by providing
      training. Importantly, the methods used in these training courses have not been
      subjected to empirical validation. In this study we evaluate a common component
      of many training programmes which encourages viewers to classify face shape. Our
      results show very low agreement in face shape classification, both within and
      between participants, and across repeated presentations of a single image to a
      single participant. Furthermore, face shape classification training did not
      improve face matching accuracy, suggesting that the face shape strategy does not
      facilitate identification.

PMID- 24919355
TI  - Familiarity, expertise, and change detection: change deafness is worse in your
      native language.
AB  - We first replicated the language-familiarity effect for voice discrimination and
      found better voice discrimination in familiar languages. However, when listeners
      were not cued to listen for changes, both English and Spanish speakers exhibited
      greater change deafness in their familiar language. Results suggest that
      lexical/semantic attention in a familiar language and increased indexical
      processing in an unfamiliar language can produce greater change deafness in
      familiar languages.

PMID- 24919356
TI  - Time-to-contact estimation modulated by implied friction.
AB  - The present study demonstrated that friction cues for target motion affect time
      to-contact (TTC) estimation. A circular target moved in a linear path with a
      constant velocity and was gradually occluded by a static rectangle. The target
      moved with forward and backward spins or without spin. Observers were asked to
      respond at the time when the moving target appeared to pass the occluder. The
      results showed that TTC was significantly longer in the backward spin condition
      than in the forward and without-spin conditions. Moreover, similar results were
      obtained when a sound was used to imply friction. Our findings indicate that the
      observer's experiential knowledge of motion coupled with friction intuitively
      modulated their TTC estimation.

PMID- 24919357
TI  - [Realities and life projects of homeless people: when the body is the last
      resource].
AB  - In today's society, the most destitute, and particularly those forced to live
      outdoors, are deprived of everything: work, money, accommodation,family, etc.
      Their body is the sole and last resource they have, but is subject to over
      exploitation in response to the physical and social survival environment in which
      they live. Many homeless people have a chaotic life trajectory, often starting in
      childhood, leaving them with little hope for improvement. How can we adapt
      medical and social care to each individual? All members of society must question
      their place and function if precariousness is to bedealt with effectively.

PMID- 24919358
TI  - [Homelessness: psychological and behavioral issues].
AB  - Risk factors lead to social exclusion and their accumulation can lead to
      homelessness. This inevitably contributes to a progressive increase in
      psychological distress or aggravates a pre-existing mental illness. Over the
      years, homeless people, who are never happy, develop various survival strategies
      and mental defenses that can sometimes prove effective. Other individuals who are
      less"adapted" to living in the street may suffer from both mental and physical
      collapse. Proactive programs designed to facilitate access to healthcare and
      welfare have been created in order to offer solutions designed to enable homeless
      people to leave the street, through access to medical care, accommodation and
      civil rights. The psychiatric sector has been slow to adapt to the needs of this
      population, although several teams specializing in mental illness and
      precariousness have been created These teams explore every possible avenue to
      help homeless people with mental health issues to recover a psychological balance
      that allows them to choose a recovery pathway and thus to regain a dignified
      lifestyle.

PMID- 24919359
TI  - [Health of the homeless].
AB  - The homeless population is difficult to define and its number difficult to
      evaluate. In France, it is estimated that almost 4 million people living in
      substandard accommodation, and 85,000 homeless people. Most homeless people
      rarely frequent public spaces. One-third have a job, one-quarter live with
      children, and one-third are between 18 and 29 years old. Shared characteristics
      include a collapse of social ties and a complete lack of stable accommodation.
      There are no illnesses specific to homeless people, but their epidemiology
      differs from the general population: the incidence rate of tuberculosis is 30
      times higher, for example. Medical care often arrives far too late. As a result,
      functional deficits are common, often following serious accidents, and
      hospitalization is three times more frequent. A chronic disease is present in 45%
      of cases. Average life expectancy is only 47.6 years-between 30 and 35 years
      lower than for the general French population. Medical care can only be fully
      effective if these patients' social and housing issues are dealt with too.

PMID- 24919360
TI  - [Historical cohorts: contribution to epidemiological knowledge].
AB  - Several large cohort studies have been performed in France since the 1960s.
      Participants were recruited from general or occupational populations. Whatever
      their primary objective, these cohort studies provided important data on the
      prevalence and risk factors of major public health problems. The scientific value
      of these studies, which gave rise to a very large numbers of publications, is
      internationally recognized.

PMID- 24919361
TI  - [Population-based cohorts. Example of the Gazel and Constances cohorts].
AB  - Population-based cohorts focus on the causes of diseases, especially
      multifactorial diseases. Some are very large, and prospectively collect personal,
      lifestyle, occupational and environmental data over several decades. All include
      biobanks. "Generalist" cohorts cover a large field of diseases and risk factors.
      Two examples are presented here The Gazel cohort was composed of 20,000 subjects
      aged 35-50 at enrolment andfollowed-up for 25 years, resulting in about 200
      publications. The Constances cohort, created in 2012, aims to include a
      representative sample of 200,000 adults aged 18-69 at enrolment.

PMID- 24919362
TI  - [Large health cohorts in France].
AB  - A cohort is composed of a group of individuals sharing a number of features and
      who are monitored longitudinally, at the individual level, according to a pre
      established protocol. Since 2008, funding of health cohorts in France by Tres
      Grandes Infrastructures de Recherche (Very Large Research Infrastructures, TGIR)
      and associated public stimulus investments has led to the creation of 15 very
      large cohorts involving either the general population or patients with particular
      diseases. As platforms for research in life sciences and health, these cohorts,
      funded for ten years, will develop shareable databases. Many health issues,
      especially biological, medical, social and environmental disease determinants and
      their interactions, will benefit from innovative approaches. Parallel
      constitution of biobanks and the use of new technologies for communication, data
      sharing and international cooperation will reinforce this initiative. A new
      longitudinal and systematic approach is strengthening the research
      infrastructure.

PMID- 24919363
TI  - [Registries of birth defects: a tool for monitoring, research, and evaluation of
      interventions].
AB  - This article examines the role of public health registries, based on the example
      of congenital abnormalities. In addition to their main role in epidemiological
      surveillance, registries can be useful for conducting research and for evaluating
      public health interventions such as primary prevention and prenatal diagnosis.
      Congenital abnormalities are relatively frequent, affecting about 3% of births,
      but many are due to rare diseases. Known teratogens increase the risk of one or
      afew specific, often rare anomalies. Consequently, continuous monitoring of
      large, geographically defined populations is needed, particularly to establish
      the "baseline "prevalence of birth defects. Networks of registries can make an
      important contribution to this goal, as exemplified by the EUROCAT network, which
      plays a key role in coordinating surveillance and research on birth defects in
      Europe.

PMID- 24919364
TI  - [Blood platelets].
AB  - Studies of inherited platelet disorders have led to major advances in our
      knowledge of platelet physiology, thus permitting the development of antiplatelet
      agents that are now widely used to treat vascular diseases. New therapeutic
      strategies have also resulted from a better understanding of
      megakaryocytopoiesis, notably including the use of thrombopoietin analogs for
      immune thrombocytopenias.

PMID- 24919365
TI  - [Glycoproteins, inherited diseases of platelets, and the role of platelets in
      wound healing].
AB  - Recognition that platelets have a glycocalyx rich in membrane glycoproteins
      prompted the discovery in France that inherited bleeding syndromes due to defects
      of platelet adhesion and aggregation were caused by deficiencies in major
      receptors at the platelet surface. Identification of the alpha IIb beta3 integrin
      prompted the development of powerful anti-thrombotic drugs that have gained
      worldwide use. Since these discoveries, the genetic causes of many other defects
      of platelet function and production have been elucidated, with the identification
      of an ADP receptor, P2 Y12, another widespread target for anti-thrombotic drugs.
      Discovery of the molecular basis of a rare disease of storage of biologically
      active proteins in platelet alpha-granules has been accompanied by the
      recognition of the roles of platelets in inflammation, the innate immune system
      and tissue repair, opening new avenues for therapeutic advances.

PMID- 24919366
TI  - [Molecular mechanisms of platelet activation].
AB  - The main role of blood platelets is to ensure vascular integrity and hemostasis
      in case of vascular damage. The platelet functions involved in these
      physiological processes are also at work in arterial thrombosis, which is a
      dramatic complication of atherosclerosis that may lead to vascular occlusion.
      These functions of platelets include their ability to adhere to the injured
      vessel wall, to be activated by contact with various substrates and soluble
      activators, and to form aggregates stabilized by a fibrin network. Platelets are
      also involved in metastasis, various inflammatory processes, innate and adaptive
      immune defenses, and embryonic development. These roles are supported by multiple
      molecular mechanisms, some of which are common to several functions while others
      are distinct. Defects in one or other of these mechanisms do not necessarily
      disrupt all platelet functions.

PMID- 24919367
TI  - [Antiplatelet agents].
AB  - Atherothrombosis is a major global public health problem. Chronic atherosclerotic
      disease is often clinically silent and coexists across multiple vascular beds
      but, when complicated by thrombosis, it can result in an acute coronary syndrome,
      stroke, transient ischemic attack, and critical limb ischemia. Platelets play a
      role in the development of chronic atherosclerotic disease and are a key mediator
      of clinical events in atherothrombosis. Numerous clinical trials have tested
      antiplatelet agents for primary and secondary prevention, and several new
      antiplatelet drugs are under development. There is evidence of clear benefit of
      single and, in some cases, dual antiplatelet therapy in the prevention of
      recurrent cardiovascular and cerebrovascular complications. Dual antiplatelet
      therapy has emerged as the standard of care for acute coronary syndromes, with
      aspirin typically being used in combination with clopidogrel or one of the newer
      more potent ADP receptor antagonists (ticagrelor or prasugrel). Conversely, in
      chronic stable coronary disease, no benefit of dual antiplatelet therapy has yet
      been convincingly demonstrated Evidence supporting routine use of aspirin or any
      other antiplatelet agent for primary prevention is mixed, and this strategy
      should only be considered for individual high-risk patients in whom the
      thrombotic risk outweighs the risk of major bleeding complications.

PMID- 24919368
TI  - [Platelets, atherothrombosis, antiplatelet drugs and cerebral ischemia].
AB  - Platelets play a much more important role in myocardial ischemia than in cerebral
      ischemia, because atherothrombosis - the underlying cause of the vast majority of
      myocardial infarcts - is responsible for only 25-30% of cerebral infarcts.
      Aspirin is the only effective antiplatelet drug for primary prevention of
      ischemic events, especially those affecting the heart. For secondary prevention
      of cerebral infarction, clopidogrel and the combination of aspirin with extended
      release dipyridamole are both marginally better than aspirin alone, but aspirin
      remains the gold standard worldwide because of its remarkable
      cost/benefit/tolerability ratio. The clopidogrel-aspirin combination is to be
      avoided because of the risk of hemorrhage, particularly in the brain and
      gastrointestinal tract. Revascularization strategies and the choice of
      antiplatelet drugs for the acute phase of myocardial and cerebral ischemia are
      very different, consisting of endovascular treatment and aggressive platelet
      inhibition for coronary infarcts, versus intravenous thrombolysis and / or
      aspirin for cerebral infarcts. None of the new antiplatelet drugs used in acute
      coronary syndromes has so far been studied in acute cerebral ischemia.

PMID- 24919369
TI  - [Megakaryopoiesis: regulation of platelet production by thrombopoietin].
AB  - Each day, 2x10(11) platelets are produced in the human body by a highly regulated
      mechanism. The biology of platelet formation is unique, as platelets arise from
      cytoplasmic fragmentation of their marrow precursor, the megakaryocyte (MK). MKs
      are giant cells that undergo polyploidisation during maturation, through a
      process called endomitosis leading to a cell with a 2(x)N DNA content. This huge
      size allows each MK to produce several thousand platelets. MK cytoplasmic
      fragmentation is a dynamic and organized process beginning with extensions,
      called proplatelets, that further fragment to give rise to platelets. This last
      process takes place in the bloodstream and is regulated by shear stress.
      Thrombopoietin (TPO) is the hormone that, with the exception of platelet
      shedding, regulates all the steps of megakaryopoiesis, from the hematopoietic
      stem cell to MK maturation. TPO is mostly synthesized by the liver, mainly in
      constitutive fashion, and its plasma level is dependent on its clearance by
      platelets and MK after binding to its receptor MPL. MPL is a type I homodimeric
      cytokine receptor that requires the kinase JAK2 for its signaling activity. MPL
      and JAK2 are involved in numerous inherited and malignant disorders leading to
      thrombocytopenia and aplastic anemia or to thrombocytosis. They are now being
      targeted therapeutically.

PMID- 24919370
TI  - [Immune thrombocytopenias: pathophysiology and treatment].
AB  - Immune thrombocytopenia (ITP) is characterized by platelet destruction due to the
      presence of platelet antibodies. This phenomenon is associated with impaired
      platelet production by bone marrow. Short-course corticosteroids and high-dose
      intravenous immunoglobulins remain the first-line treatments. Several
      international guidelines propose splenectomy as a second-line treatment for
      chronic ITP. However, new therapeutic strategies including anti-CD20 monoclonal
      antibodies and thrombopoietin receptor agonists, appear to be very effective and
      to have good short-term tolerability. Prospective studies that include safety,
      efficacy and medico-economic assessments are needed to refine the management of
      chronic ITP.

PMID- 24919371
TI  - [Blood platelets: conclusion].

PMID- 24919372
TI  - [Psychogenic contracture, a trap for the orthopedic surgeon].
AB  - Dysfunctional posture is an enigmatic pathological entity now attributed to a
      conversion reaction (formerly to hysteria). When localized to the limbs, the main
      clinical feature is a contracture of one or several articular segments inflexion
      or extension. Most of the time, the contracture is released by anesthesia.
      Patients should be managed with a psychopathological approach. However, some
      patients continue to be managed in a surgical department because the contracture
      became apparent after a trauma or surgical procedure. The orthopedic surgeon must
      be aware of this phenomenon in order to avoid unnecessary operations.

PMID- 24919373
TI  - [Does early signet ring cell gastric carcinoma carry a worse prognosis?].
AB  - INTRODUCTION: The signet ring cell (SRC) histological subtype is a factor of poor
      prognosis in advanced gastric adenocarcinomas, but its prognostic value in early
      gastric cancer is unclear. The aim of this study was to evaluate the prognostic
      impact of SRC in superficial gastric adenocarcinomas, based on a comparison of
      patients with SRC and non SRC histologies. PATIENTS AND METHODS: From a large
      national cohort of 3,010 patients operated on for gastric adenocarcinoma between
      January 1997 and January 2010, we selected patients with pTis or pT1 tumors and
      compared those with SRC and non SRC histology on the basis of demographic,
      surgical and histologic factors and outcomes. The primary endpoint was the 3-year
      survival rate. RESULTS: Among 421 patients with a pTis or pT1 tumor, 104 (24.7%)
      had the SRC subtype and 317 (75.3%) a non SRC subtype. Median age was
      significantly lower in the SRC group than in the non SRC group (59.6 vs 68.8
      years, p<0.001). Other demographic variables were similar in the two groups.
      Extensive surgical resection was more frequent in the non SRC group (31.9% vs
      12.5%, p<0.001), but R0 resection rates were similar (97.5% vs 98.1%, p=0.900).
      The submucosa was more frequently involved in the SRC group (94.2% vs 84.9%,
      p=0.043), while lymph node involvement and the number of invaded nodes were
      similar in the two groups. Recurrences (5.8% vs 8.8%, p=0.223) and sites of
      recurrence (especially peritoneal carcinomatosis, 1.9% vs 1.6% ; p=0.838) were
      similar in the two groups. The 3-year survival rate was similar in the SRC and
      non SRC groups (94.1% vs 89.9%, p=0. 403), although the median survival time had
      not been reached CONCLUSION: SRC is not a prognostic factor in superficial
      gastric adenocarcinoma.

PMID- 24919374
TI  - [Surgery for anal incontinence: developments in the past two decades and future
      directions].
AB  - Studies showing the frequency of anal incontinence and its social and economic
      impact have driven progress in surgical treatment, from muscle repair by
      myorraphy (mainly posterior myorraphy) or sphincteroplasty by direct suture of
      the external anal sphincter some 20 years ago, to invasive surgery with
      implantation of an artificial anal sphincter in 1993, mini-invasive surgery based
      on sacral nerve stimulation in 1998, failure of mini-invasive procedures with
      injection of a bulking agent or radiofrequency in 2000-2010, and development in
      2012 of cellular therapy based on injection of autologous myoblasts. Progress in
      functional gut exploration (anorectal manometry, electrophysiological tests,
      endoanal ultrasonography, MRI, colonic transit time) and better knowledge of
      colonic and ano-rectal physiology will lead to further surgical advances.

PMID- 24919375
TI  - [Controlled drug consumption rooms].

PMID- 24919376
TI  - [Free screening and semi-private hearing aid schools: a paramedical market].

PMID- 24919377
TI  - [Cardiovascular risk, cholesterol and statins].

PMID- 24919378
TI  - [Absinthe rehabilitated].
AB  - Absinthe (Artemisia absinthium) has been known for its medicinal properties since
      Antiquity. The Egyptians in 1600 BC, then Hippocrates, Galien, The Salerne School
      in 1649, and 18th-century physicians all recommended it for a variety of
      maladies. In 1780-1790 in Switzerland (Val de Travers), a traditional healer and,
      probably, a itinerant physician by the name of Docteur Ordinaire, transformed
      this purgative elixir into an aperitif liqueur, a move followed by two centuries
      of unexpected success. Absinthe was manufactured in France, at Pontarlier, for
      tax reasons. In 1900, the town counted 25 distilleries. Its production then
      extended to other French provinces. La fee verte ("green fairy") was particularly
      popular with the military, literary and artistic circles, and, finally the
      general public. In 1902, following a parliamentary vote, the Minister of the
      Interior asked the National Academy of Medicine to issue an opinion on "The
      indication of aperitif liqueurs, including absinthe". The Commission on
      Alcoholism, chaired by J.V. Laborde, examined the composition of absinthe
      liqueurs, the physiological and toxic action of their essences, the risks
      associated with "bitter" aperitifs, and the composition of essence-based liqueurs
      that were not used as aperitifs. The Commission compiled a list of the most
      dangerous aperitifs and liqueurs placing absinthe at the top, and recommended
      that the authorities prohibit the manufacture, circulation, advertisement and
      sale of all such drinks, including absinthe. However, because these drinks, and
      especially absinthe, represented an important source of tax revenue, this
      recommendation was only acted upon 13 years later, with a law adopted in March
      1915. Despite subsequent prohibition of the production of absinthe liqueur,
      manufacturers in the Val de Travers region and a distillery in Pontarlier
      continued to work in secret until the prohibition was finally lifted in the year
      2000. This decision was based on scientific analyses showing that thuyone was
      only toxic when ingested in very large amounts incompatible with normal
      consumption. In addition, it was found that the high alcohol content, often
      including adulterated alcohol, was particularly detrimental. A handful of
      manufacturers are now authorized, with strict limits placed on the alcohol
      content and thuyone concentration. Does this mean that the Academy of Medicine
      was wrong? While the report can be criticized, the fight against alcoholism was a
      worthy and necessary cause at the time, and remains so today.

PMID- 24919379
TI  - Cockpit displays of traffic information and pilot bias in time-to-contact
      judgments.
AB  - INTRODUCTION: Pilots are susceptible to over-reliance on distance when making
      relative time-to-contact (TTC) judgments of surrounding intruders, referred to as
      "the distance bias." We tested the effect of adding perceptual cues and an
      information feature to cockpit displays of traffic information to mitigate this
      bias. METHOD: There were 14 general aviation pilots who participated in a
      simulated flight scenario and were asked to make relative TTC judgments. Three
      levels of perceptual cue (blinking, color-change, and no-cue) were crossed with
      two levels of velocity data tag (present and absent) with identification of the
      highest risk intruder as a response. RESULTS: Perceptual cues were associated
      with more accurate high-risk intruder selection (color = 95.95% correct, blinking
      = 95.98%, no-cue = 87.89%), decreased response time (color = 3.68 s, blinking =
      3.19 s, no-cue = 6.08 s), reduced visual attention demand (color = 57% of
      attention, blinking = 58%, no-cue = 62%), lower workload ratings (color =
      28.38/100, blinking = 29.66/100, no-cue = 48.91/100), and higher performance
      confidence ratings (color = 83.92/100, blinking = 82.71/100, no-cue = 58.85/100)
      than the no-cue displays. There was no difference between blinking and color cue
      displays. The data tag was associated with lower response times (present = 4.13
      s, absent = 4.50 s) and higher confidence ratings (present = 78.69/100, absent =
      71.63/100) than displays without. Displays including the blinking cue, color
      change cue, and data tag were preferred over displays that did not include these
      features (color = 8 pilots, blinking = 6, no-cue = 0). DISCUSSION: The added
      display features were effective in mitigating the effect of the distance bias on
      pilot performance measures and received favorable subjective ratings.

PMID- 24919380
TI  - Isometric force exaggeration in simulated weightlessness by water immersion: role
      of visual feedback.
AB  - BACKGROUND: Previous studies reported that humans produce exaggerated isometric
      forces (20-50%) in microgravity, hypergravity, and under water. Subjects were not
      provided with visual feedback and exaggerations were attributed to proprioceptive
      deficits. The few studies that provided visual feedback in micro- and
      hypergravity found no deficits. The present work was undertaken to find out
      whether visual feedback can reduce or eliminate isometric force exaggerations
      during shallow water immersion, a working environment for astronauts and divers.
      METHODS: There were 48 subjects who had to produce isometric forces of 15 N with
      a joystick; targets were presented via screen. Procedures were similar to earlier
      studies, but provided visual feedback. Subjects were tested 16.4 ft (5 m) under
      water (WET) and on dry land (DRY). Response accuracy was calculated with
      landmarks such as initial and peak force magnitude, and response timing. RESULTS:
      Initial force and response timing were equal in WET compared to DRY. A small but
      significant force exaggeration (+5%) remained for peak force in WET that was
      limited to directions toward the trunk. DISCUSSION: Force exaggeration under
      water is largely compensated, but not completely eliminated by visual feedback.
      As in earlier studies without visual feedback, force exaggeration manifested
      during later but not early response parts, speaking for impaired proprioceptive
      feedback rather than for erroneous central motor planning. Since in contrast to
      micro/hypergravity, visual feedback did not sufficiently abolish force deficits
      under water, proprioceptive information seems to be weighted differently in
      micro/hypergravity and shallow water immersion, probably because only the latter
      environment produces increased ambient pressure, which is known to induce
      neuronal changes.

PMID- 24919381
TI  - The metabolic cost of an integrated exercise program performed during 14 days of
      bed rest.
AB  - BACKGROUND: Exercise countermeasures designed to mitigate muscle atrophy during
      long-duration spaceflight may not be as effective if crewmembers are in negative
      energy balance (energy output > energy input). This study determined the energy
      cost of supine exercise (resistance, interval, aerobic) during the spaceflight
      analogue of bed rest. METHODS: Nine subjects (eight men and one woman; 34.5 +/-
      8.2 yr) completed 14 d of bed rest and concomitant exercise countermeasures. Body
      mass and basal metabolic rate (BMR) were assessed before and during bed rest.
      Exercise energy expenditure was measured during and immediately after [excess
      post-exercise oxygen consumption (EPOC)] each of five different exercise
      protocols (30-s, 2-min, and 4-min intervals, continuous aerobic, and a variety of
      resistance exercises) during bed rest. RESULTS: On days when resistance and
      continuous aerobic exercise were performed daily, energy expenditure was
      significantly greater (2879 +/- 280 kcal) than 2-min (2390 +/- 237 kcal), 30-s
      (2501 +/- 264 kcal), or 4-min (2546 +/- 264 kcal) exercise. There were no
      significant differences in BMR (pre-bed rest: 1649 +/- 216 kcal; week 1: 1632 +/-
      174 kcal; week 2:1657 +/- 176 kcal) or body mass (pre-bed rest: 75.2 +/- 10.1 kg;
      post-bed rest: 75.2 +/- 9.6 kg). DISCUSSION: These findings highlight the
      importance of energy balance for long-duration crewmembers completing a high
      intensity exercise program with multiple exercise sessions daily.

PMID- 24919382
TI  - Control pattern injuries in fatal fixed-wing general aviation accidents.
AB  - BACKGROUND: In aviation accident investigations, control pattern injuries (CPIs)
      have been useful for accident reconstruction and for determining who was in
      control of the aircraft at the time of impact. Recently, CPIs have been
      considered nonspecific. This study compares CPIs suffered by pilots and
      passengers in fatal fixed-wing general aviation (GA) accidents. METHODS: Accident
      data were collected from the Federal Aviation Administration's Civil Aerospace
      Medical Institute (FAA-CAMI) and National Transportation Safety Board (NTSB)
      accident reports for the year 2010. Pilot and passenger data were analyzed by
      comparing the number, type, and location of CPIs. RESULTS: Of 22 types of CPIs, 2
      were found to be individually statistically significant, but neither was
      significant when corrected for multiple comparisons. When comparing solo pilots
      to all passengers, fractures of the right metatarsals occurred more frequently in
      solo pilots (9.3%) than in all passengers (1.69%) and fractures of the distal
      radius and ulna occurred less frequently for solo pilots (11.36%) than in all
      passengers (22.41%). CONCLUSION: Proportional differences appear to exist when
      comparing specific CPIs between pilots and passengers. Control pattern injuries
      are an important part of accident investigation and may be helpful in determining
      the pilot in control at the time of impact.

PMID- 24919383
TI  - Variability in orthostatic tolerance during heat stress: cerebrovascular
      reactivity to arterial carbon dioxide.
AB  - INTRODUCTION: A high degree of interindividual variability exists in the
      magnitude of heat stress (HS)-induced reductions in orthostatic tolerance
      relative to normothermia (NT). This variability may be associated with HS
      mediated reductions in cerebral perfusion (indexed as middle cerebral artery
      blood velocity; MCAV(mean)) and altered cerebrovascular regulation. METHODS: We
      tested the hypothesis that cerebrovascular reactivity to hypocapnia would be
      positively correlated with differences in tolerance to lower body negative
      pressure (LBNP) [assessed with a cumulative stress index (CSI)] between HS and NT
      (CSI(diff)). Subjects (N = 13) underwent LBNP twice (NT and HS) separated by > 72
      h to assess CSI. On a third day, cerebrovascular reactivity [changes in cerebral
      vascular conductance (CVCi) during hyperventilation-induced hypocapnia (indexed
      by end tidal carbon dioxide; P(ET)CO2)] was assessed during NT, HS, and HS+LBNP (
      20 mmHg; HS(LBNP)). RESULTS: Tolerance to LBNP was reduced after a 1.5 +/- 0.1
      degrees C increase in internal temperature and a high degree of variability was
      observed for CSI(diff) (range: 122 to 1826 mmHg x min(-1)). The magnitude of
      reduction in CVCi during voluntary hyperventilation-induced hypocapnia (-16 +/- 5
      Torr) was attenuated during HS and HS(LBNP) VS. NT (NT: -0.20 +/- 0.09 cm x s(-1)
      x mmHg(-1); HS: -0.12 +/- 0.09 cm x s(-1) x mmHg(-1); HS(LBNP): -0.11 +/- 0.11 cm
      x s(-1). mmHg(-1)); however, no relationship existed between deltaCVCi/ P(ET)CO2
      and CSI(diff) in any condition. CONCLUSIONS: Cerebrovascular reactivity to
      hyperventilation-induced hypocapnia is attenuated when internal temperature is
      elevated, perhaps as a protective mechanism to protect against further reductions
      in the already diminished cerebral perfusion in this thermal state. However,
      individual differences in these responses do not appear to predict orthostatic
      tolerance during HS.

PMID- 24919384
TI  - Fatal accident rates for instrument-rated private pilots.
AB  - BACKGROUND: The fatality rate for general aviation, 82 times that of air carriers
      and even higher for those involving aeromedical transportation, has not declined
      over time. Although noncommercial (private) pilots are increasingly seeking the
      instrument rating (IFR), which offers safety advantages, there is a paucity of
      research on causes of fatal crashes for this aviator subset. METHODS: The NTSB
      accident database was queried for general aviation fatal accidents involving
      private pilots. Exact two sample proportions, linear regression model outcomes
      (log-odds), and Poisson rate ratio tests were used for statistical analysis.
      RESULTS: The fatal accident rate for flights in instrument conditions decreased
      55% over 10 yr (2002-2011) although an increased fatality rate was evident for
      pilots > 65 yr of age. Instrument approach deficiency (lAD), spatial
      disorientation/failure to maintain control (SD/FMC), and failure to maintain
      obstacle/terrain clearance (FMOTC) were common causes of fatal accidents in
      reduced visibility. However a > 55% decline in fatal accidents due to IAD was
      evident over the decade. Under visual conditions, engine/air-frame malfunction,
      aerodynamic stall, and FMOTC represented frequent causes. Of these, FMOTC showed
      a statistically significant decline over 10 yr. Comparing day and night
      operations, fatal crashes attributed to FMOTC and IAD were more frequent at
      night. CONCLUSION: For the IFR-rated private pilot, our study argues for an
      emphasis on training and currency in SD/FMC and aerodynamic stall recovery.
      Likewise training to remedy IAD, the frequent cause of fatal night accidents, and
      flying by instrument flight rules to assure obstacle/terrain clearance should be
      encouraged for pilots undertaking such operations.

PMID- 24919385
TI  - Space motion sickness countermeasures: a pharmacological double-blind, placebo
      controlled study.
AB  - INTRODUCTION: Space motion sickness (SMS), caused by a canal-otolith conflict, is
      currently treated with intramuscular promethazine. However, the drug has an
      inconsistent efficacy against SMS. We hypothesize that pharmacological depression
      of the semicircular canals (SCC) might relieve SMS. The aim of the present study
      was to identify the effects of meclizine (25 mg), dimenhydrinate (40 mg) combined
      with cinnarizine (25 mg), and promethazine (25 mg) combined with d-amphetamine
      (10 mg) on the SCCs and the otoliths. METHODS: This double-blind, placebo
      controlled study was performed on 20 healthy men. Function of the SCC was
      evaluated by means of an electronystagmography, whereas utricular function was
      assessed by a unilateral centrifugation test. A cervical vestibular evoked
      myogenic potentials test evaluated saccular function. RESULTS: Meclizine (0.54 +/
      0.05 vs. 0.38 +/- 0.06) and dimenhydrinate with cinnarizine (0.54 +/- 0.05 vs.
      0.45 +/- 0.05) decreased the vestibulo-ocular reflex gain. Promethazine with d
      amphetamine decreased the latency of the saccadic eye response (right eye: 185 +/
      3.8 ms vs. 165 +/- 4.5 ms; left eye: 181 +/- 4.9 ms vs. 165 +/- 4.8 ms) and also
      increased the phase of ocular counterrolling measured during unilateral
      centrifugation (0.32 +/- 0.35 degrees vs. 1.5 +/- 0.45 degrees). DISCUSSION: It
      is hypothesized that meclizine and dimenhydrinate with cinnarizine affect the
      medial vestibular nucleus. Promethazine is a vestibular suppressor, but study
      results show that d-amphetamine counterbalances this depression and abolishes the
      effect of fatigue on the saccadic reaction time The hypothesis that a SCC
      suppression alleviates SMS should be further evaluated.

PMID- 24919386
TI  - Women's health in spaceflight.
AB  - OBJECTIVE: To review the current state of knowledge with regards to clinical
      challenges related to women's health during spaceflight. METHODS: Articles were
      reviewed relevant to "women", "sex," and "gender" in "microgravity,"
      "weightlessness," and "spaceflight" in the English and Russian languages.
      RESULTS: There were 50 papers identified. Studies have shown that crewmembers
      suffer from space motion sickness, but gender discrepancies have not been
      explored. Nearly all women experience orthostatic intolerance in space, which may
      be due to differences in female cardiovascular response. Immunosuppression in
      spaceflight results in susceptibility to opportunistic infections, but no studies
      have investigated gender differences. Finally, radiation exposure and germ cell
      viability influence the reproductive health of astronauts. CONCLUSIONS: With
      changes in space access offered by commercial space activities, research areas
      devoted to women's health in microgravity should become one of the priorities for
      safe space exploratory efforts.

PMID- 24919387
TI  - Electrocardiogram at an altitude of 3600 m with reference to T wave depression.
AB  - INTRODUCTION: Exposure to high altitude decreases arterial oxygen saturation
      (Sa(O2)). Previous studies have shown decreased voltage of the T wave of the
      electrocardiogram (ECG) at altitudes up to 7000 m (22,966 ft) secondary to
      hypoxia. This pilot study explored changes in the ECG at the maximum altitude
      pilots can fly without supplemental oxygen. In addition, this is a common
      altitude for recreational trekkers. METHODS: There were 13 subjects who rested at
      sea level (1ATA) for 30 min and then were taken to an altitude of 3000 m or 3600
      m (10,000 or 12,000 ft; at altitude) where they rested for 30 min. ECG was
      collected continuously as was Sa(O2) and heart rate (HR). A series of 10 ECG
      complexes were analyzed for 7 time periods over the 30-min collection periods.
      RESULTS: The P wave, PR, QRS, and QT interval duration did not show a significant
      difference between 1 ATA and at altitude for the group of subjects analyzed (N =
      11 ). The T wave amplitude showed a significant decrease (delta = -19.3%) for
      seven subjects at altitude; however, the other six subjects did not show a
      significant change (delta = 1.6%). The T wave amplitude observations described
      above were consistent for average HRs and selected HRs that were equal between 1
      ATA and at altitude. CONCLUSION: This study confirmed that some subjects showed
      decreased T wave amplitude at altitude which was not associated with pulmonary
      function, HR, ventilation, end-tidal CO2, or Sa(O2).

PMID- 24919388
TI  - Yawning as a behavioral marker of mild motion sickness and sopite syndrome.
AB  - INTRODUCTION: Severe motion sickness is easily identifiable with sufferers
      showing obvious behavioral signs, including emesis (vomiting). Mild motion
      sickness and sopite syndrome lack such clear and objective behavioral markers. We
      postulate that yawning may have the potential to be used in operational settings
      as such a marker. This study assesses the utility of yawning as a behavioral
      marker for the identification of soporific effects by investigating the
      association between yawning and mild motion sickness/sopite syndrome in a
      controlled environment. METHODS: Using a randomized motion-counterbalanced
      design, we collected yawning and motion sickness data from 39 healthy individuals
      (34 men and 5 women, ages 27-59 yr) in static and motion conditions. Each
      individual participated in two 1-h sessions. Each session consisted of six 10-min
      blocks. Subjects performed a multitasking battery on a head mounted display while
      seated on the moving platform. The occurrence and severity of symptoms were
      assessed with the Motion Sickness Assessment Questionnaire (MSAQ). RESULTS:
      Yawning occurred predominantly in the motion condition. All yawners in motion (N
      = 5) were symptomatic. Compared to nonyawners (MSAQ indices: Total = 14.0, Sopite
      = 15.0), subjects who yawned in motion demonstrated increased severity of motion
      sickness and soporific symptoms (MSAQ indices: Total = 17.2, Sopite = 22.4), and
      reduced multitasking cognitive performance (Composite score: nonyawners = 1348;
      yawners = 1145). DISCUSSION: These results provide evidence that yawning may be a
      viable behavioral marker to recognize the onset of soporific effects and their
      concomitant reduction in cognitive performance.

PMID- 24919389
TI  - Unexplained hypoxia in an in-flight emergency.
AB  - BACKGROUND: The use of over-the-counter medications and nutritional supplements
      is prohibited while flying without approval from an aeromedical professional.
      Despite prohibition, the use of nutritional supplements is common in aircrew due
      to the perception that these supplements are harmless; in reality, the use of
      nutritional supplements may be more dangerous than the use of traditional
      medications. Multiple case reports of adverse neurologic and cardiovascular
      events associated with the use of specific supplements led the FDA to ban ephedra
      in 2004 and DMAA in 2012, both marketed as "natural stimulants." These incidents
      are sobering reminders of the lack of safety data on commonly marketed
      nutritional supplements. There are few, if any, case reports or clinical trials
      addressing the safety of common nutritional supplements in flight. CASE REPORT:
      This is a case of an aircrew member who experienced hypoxia during an in-flight
      emergency. He underwent thorough medical evaluation to determine the cause of his
      hypoxic event and ultimately admitted to the use of a pre-workout supplement: C4
      Extreme. He was exposed to simulated altitude both on and off of the supplement
      and was found to have an improved tolerance to a hypoxic environment after
      discontinuation. DISCUSSION: While not conclusive, the data suggests that the use
      of C4 Extreme may be implicated in this aircrewman's increased susceptibility to
      hypoxia. A randomized controlled trial would be required to determine if this is
      a patient-specific response or if this is a normal physiologic response to the
      use of this and similar supplements.

PMID- 24919390
TI  - A new equation for calculating the maximum wait time for pilots who use an
      impairing medication.
AB  - INTRODUCTION: Pilots who use an impairing medication to treat a medical condition
      are required to wait an appropriate amount of time after completing the treatment
      before returning to duty. However, toxicology findings from fatal aviation
      accidents indicate not all pilots wait a sufficient period of time. Methods used
      today do not take into consideration the time required for the drug to reach
      subtherapeutic concentrations. METHODS: An equation was developed based on the
      therapeutic range and the maximum expected half-life of the medication to
      objectively calculate a safe return-to-duty time for pilots. The new equation
      assumes the treating physician will not dose the patient beyond the upper
      therapeutic range of the medication and the person taking the medication has the
      maximum half-life reported in the literature. The equation N
      ln(0.5*Cmin/Cmax)/ln(0.5) was developed to determine the number of half-lives (n)
      required to reach one-half of Cmin, where Cmin = lower therapeutic concentration
      and Cmax = upper therapeutic concentration. Anonymous subjects were recruited
      under an approved IRB protocol. Blood and plasma were collected at approximately
      Cmax (2-3 h) and again after waiting approximately another 5 h. Toxicological
      analysis was performed on the specimens collected. RESULTS: One subject taking a
      25-mg dose had a 0.033 ug x ml(-1) blood concentration after waiting 8 h, well
      above the 0.025 ug x ml(-1) reported as impairing concentration. The new equation
      estimated a mean wait time for the 18 medications composed of 4 half-lives.
      DISCUSSION: The new CAMI equation takes into consideration safety without grossly
      over estimating pilot wait times.

PMID- 24919391
TI  - Sopite syndrome: a revised definition.
AB  - In 1976, Graybiel and Knepton proposed the term "sopite syndrome" to describe a
      symptom complex centering on drowsiness and lethargy related to motion sickness.
      However, existing descriptions and definitions of sopite syndrome have
      limitations in fully conveying the appropriate information to the reader. Our
      objective is to propose a revised definition providing a more adequate conceptual
      framework for research. The proposed definition of sopite syndrome addresses the
      nonspecificity of soporific symptoms, the health state of the individuals, and
      the existence of a motion stimulus.

PMID- 24919392
TI  - You're the flight surgeon: acoustic neuroma.

PMID- 24919393
TI  - You're the flight surgeon: the complex patient.

PMID- 24919394
TI  - The month in aerospace medicine history.

PMID- 24919395
TI  - Make a difference through AsMA.

PMID- 24919396
TI  - Is risk analysis scientific?
AB  - This article discusses to what extent risk analysis is scientific in view of a
      set of commonly used definitions and criteria. We consider scientific knowledge
      to be characterized by its subject matter, its success in developing the best
      available knowledge in its fields of study, and the epistemic norms and values
      that guide scientific investigations. We proceed to assess the field of risk
      analysis according to these criteria. For this purpose, we use a model for risk
      analysis in which science is used as a base for decision making on risks, which
      covers the five elements evidence, knowledge base, broad risk evaluation,
      managerial review and judgment, and the decision; and that relates these elements
      to the domains experts and decisionmakers, and to the domains fact-based or value
      based. We conclude that risk analysis is a scientific field of study, when
      understood as consisting primarily of (i) knowledge about risk-related phenomena,
      processes, events, etc., and (ii) concepts, theories, frameworks, approaches,
      principles, methods and models to understand, assess, characterize, communicate,
      and manage risk, in general and for specific applications (the instrumental
      part). 

PMID- 24919397
TI  - Inhibition of tau aggregation by a rosamine derivative that blocks tau
      intermolecular disulfide cross-linking.
AB  - Abnormal tau aggregates are presumed to be neurotoxic and are an important
      therapeutic target for multiple neurodegenerative disorders including Alzheimer's
      disease. Growing evidence has shown that tau intermolecular disulfide cross
      linking is critical in generating tau oligomers that serve as a building block
      for higher-order aggregates. Here we report that a small molecule inhibitor
      prevents tau aggregation by blocking the generation of disulfide cross-linked tau
      oligomers. Among the compounds tested, a rosamine derivative bearing mild thiol
      reactivity selectively labeled tau and effectively inhibited oligomerization and
      fibrillization processes in vitro. Our data suggest that controlling tau
      oxidation status could be a new therapeutic strategy for prevention of abnormal
      tau aggregation.

PMID- 24919398
TI  - Breast cancer risk, nightwork, and circadian clock gene polymorphisms.
AB  - Night shift work has been associated with an increased risk of breast cancer
      pointing to a role of circadian disruption. We investigated the role of circadian
      clock gene polymorphisms and their interaction with nightwork in breast cancer
      risk in a population-based case-control study in France including 1126 breast
      cancer cases and 1174 controls. We estimated breast cancer risk associated with
      each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock
      genes. We also used a gene- and pathway-based approach to investigate the overall
      effect on breast cancer of circadian clock gene variants that might not be
      detected in analyses based on individual SNPs. Interactions with nightwork were
      tested at the SNP, gene, and pathway levels. We found that two SNPs in RORA
      (rs1482057 and rs12914272) were associated with breast cancer in the whole sample
      and among postmenopausal women. In this subpopulation, we also reported an
      association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the
      analyses at the gene level. Breast cancer risk in postmenopausal women was also
      associated with overall genetic variation in the circadian gene pathway (P=0.04),
      but this association was not detected in premenopausal women. There was some
      evidence of an interaction between PER1 and nightwork in breast cancer in the
      whole sample (P=0.024), although the effect was not statistically significant
      after correcting for multiple testing (P=0.452). Our results support the
      hypothesis that circadian clock gene variants modulate breast cancer risk.

PMID- 24919399
TI  - Addressing the evidence for FDA nicotine replacement therapy label changes: a
      policy statement of the Association for the Treatment of Tobacco use and
      Dependence and the Society for Research on Nicotine and Tobacco.
AB  - Cigarette smoking creates a substantial public health burden. Identifying new,
      effective smoking cessation interventions that optimize existing interventions
      and promoting effective use of approved medications is a priority. When used as
      directed, nicotine replacement therapy (NRT) aids smoking cessation, but there is
      opportunity for improving its effectiveness. Until recently, NRT use guidelines
      advised smokers to begin using NRT on their quit date, only to use 1 NRT
      formulation at a time, to refrain from using NRT while smoking, and to stop NRT
      within 3 months regardless of progress. The Food and Drug Administration (FDA)
      issued a recent announcement allowing for NRT labeling changes with applications
      from pharmaceutical companies for such changes, and we applaud this decision.
      Nevertheless, additional revisions are warranted by current research. There is
      robust evidence that combining a longer-acting form (e.g., patch) with a shorter
      acting form (e.g., lozenge) is more effective than NRT monotherapy and is safe.
      Moreover, extant evidence suggests that NRT use prior to a quit attempt or for
      smoking reduction as part of a quit attempt is safe and as effective as starting
      NRT on quit date. Specifically, prequit nicotine patch increases quit rates and
      may engage additional recalcitrant smokers. Last, NRT use longer than 3 months is
      safe and may be beneficial for relapse prevention in some smokers. This report
      summarizes the FDA announcement, reviews the evidence for further revisions to
      current FDA NRT guidelines, and makes recommendations for over-the-counter (OTC)
      NRT labeling to allow for (1) combined use of faster-acting NRT medications with
      nicotine patch, (2) nicotine patch use prior to quit date or NRT for smoking
      reduction as part of a quit attempt, and (3) prolonged NRT for up to 6 months
      without healthcare provider consultation. 

PMID- 24919400
TI  - A homolog of lariat-debranching enzyme modulates turnover of branched RNA.
AB  - Turnover of the branched RNA intermediates and products of pre-mRNA splicing is
      mediated by the lariat-debranching enzyme Dbr1. We characterized a homolog of
      Dbr1 from Saccharomyces cerevisiae, Drn1/Ygr093w, that has a pseudo
      metallophosphodiesterase domain with primary sequence homology to Dbr1 but lacks
      essential active site residues found in Dbr1. Whereas loss of Dbr1 results in
      lariat-introns failing broadly to turnover, loss of Drn1 causes low levels of
      lariat-intron accumulation. Conserved residues in the Drn1 C-terminal CwfJ
      domains, which are not present in Dbr1, are required for efficient intron
      turnover. Drn1 interacts with Dbr1, components of the Nineteen Complex, U2 snRNA,
      branched intermediates, and products of splicing. Drn1 enhances debranching
      catalyzed by Dbr1 in vitro, but does so without significantly improving the
      affinity of Dbr1 for branched RNA. Splicing carried out in in vitro extracts in
      the absence of Drn1 results in an accumulation of branched splicing intermediates
      and products released from the spliceosome, likely due to less active
      debranching, as well as the promiscuous release of cleaved 5'-exon. Drn1 enhances
      Dbr1-mediated turnover of lariat-intermediates and lariat-intron products,
      indicating that branched RNA turnover is regulated at multiple steps during
      splicing. 

PMID- 24919402
TI  - Arrested coalescence behaviour of giant Pickering droplets and colloidosomes
      stabilised by poly(tert-butylaminoethyl methacrylate) latexes.
AB  - The coalescence of two oil droplets grown at pH 10 in the presence of lightly
      cross-linked 260 nm diameter charge-stabilised poly(tert-butylamino)ethyl
      methacrylate (PTBAEMA) latexes was monitored using a high-speed video camera.
      Three model oils (n-dodecane, isopropyl myristate and sunflower oil) were
      investigated, each in the absence and presence of an oil-soluble cross-linker
      [tolylene 2,4-diisocyanate-terminated poly(propylene glycol), PPG-TDI]. In the
      absence of PPG-TDI, rapid coalescence was observed for giant PTBAEMA-stabilised
      Pickering oil droplets, which exhibited faster coalescence times compared to bare
      oil droplets. However, an increase in the damping coefficients for coalescing
      Pickering droplets (compared to those of bare oil droplets) indicated PTBAEMA
      latex particle adsorption. Addition of PPG-TDI cross-linker to oil droplets in
      the absence of latex particles led to a reduction in the interfacial tension
      confirming its surface-active nature. The oil-soluble PPG-TDI reacts with the
      secondary amine groups on the PTBAEMA latex, producing giant colloidosomes that
      remain stable to coalescence when brought into contact. This stability to
      coalescence was not observed for bare oil droplets in the presence of PPG-TDI,
      confirming that the cross-linked latex particles at the interface provide the
      additional stability. Finally, interactions between asymmetric n-dodecane
      droplets were examined. Adding oil-soluble cross-linker to only one droplet
      resulted in "arrested coalescence" behaviour in the presence of PTBAEMA latex
      particles. In this context, the droplet ageing time was found to be critical and
      is attributed to the relatively slow particle adsorption kinetics. Ageing times
      of less than 60 s led to catastrophic droplet coalescence, whereas ageing times
      longer than 60 s indicated cross-linker diffusion from one droplet to the other,
      which produced inter-cross-linked colloidosomes. Arrested coalescence was only
      observed for ageing times of approximately 60 s. 

PMID- 24919401
TI  - Binding of human apoA-I[K107del] variant to TG-rich particles: implications for
      mechanisms underlying hypertriglyceridemia.
AB  - We found earlier that apoA-I variants that induced hypertriglyceridemia (HTG) in
      mice had increased affinity to TG-rich lipoproteins and thereby impaired their
      catabolism. Here, we tested whether a naturally occurring human apoA-I mutation,
      Lys107del, associated with HTG also promotes apoA-I binding to TG-rich particles.
      We expressed apoA-I[Lys107del] variant in Escherichia coli, studied its binding
      to TG-rich emulsion particles, and performed a physicochemical characterization
      of the protein. Compared with WT apoA-I, apoA-I[Lys107del] showed enhanced
      binding to TG-rich particles, lower stability, and greater exposure of
      hydrophobic surfaces. The crystal structure of truncated, Delta(185-243), apoA-I
      suggests that deletion of Lys107 disrupts helix registration and disturbs a
      stabilizing salt bridge network in the N-terminal helical bundle. To elucidate
      the structural changes responsible for the altered function of apoA-I[Lys107del],
      we studied another mutant, apoA-I [Lys107Ala]. Our findings suggest that the
      registry shift and ensuing disruption of the inter-helical salt bridges in apoA
      I[Lys107del] result in destabilization of the helical bundle structure and
      greater exposure of hydrophobic surfaces. We conclude that the structural changes
      in the apoA-I[Lys107del] variant facilitate its binding to TG-rich lipoproteins
      and thus, may reduce their lipolysis and contribute to the development of HTG in
      carriers of the mutation. 

PMID- 24919403
TI  - Osteoinduction of biphasic calcium phosphate scaffolds in a nude mouse model.
AB  - Bioceramics combined with isolated stem cells, or with total bone marrow,
      constitute the main strategies under consideration in the field of bone tissue
      engineering. In the present preclinical study, two biphasic calcium phosphate
      scaffolds currently on the market, MBCP(r) and MBCP+(r), with different
      hydroxyapatite/beta-tricalcium phosphate ratio, were implanted ectopically in a
      nude mouse model. These scaffolds were supplemented either with human mesenchymal
      stromal cells, or with human total bone marrow, or rat total bone marrow.
      Biomaterials alone were found to have potentially low, but non-zero,
      osteoinductive properties, while biomaterials associated with total bone marrow
      consistently improved osteoinduction in comparison with high concentrations of
      isolated human stromal cells. 

PMID- 24919404
TI  - Molecular taxonomic identification in the absence of a 'barcoding gap': a test
      with the endemic flora of the Canarian oceanic hotspot.
AB  - We use a comprehensive subset of Canarian angiosperms corresponding to 23
      families, 35 genera and 60 Canarian endemic taxa to test whether this flora is
      suitable to taxonomic identification with the two proposed plant DNA barcode
      sequences and whether these sequences may reveal the existence of cryptic species
      overlooked by morphology. The rate of discrimination success between the insular
      congeneric samples using the rbcL+matK combination and a 'character-based'
      approach (where we use only the combination of nucleotide positions in an
      alignment that allows unambiguous species identification) is higher (82.29%) than
      that obtained with the 'distance-based' approach (80.20%) used by the CBOL Plant
      Working Group in 2009 and also when compared with tests conducted in other
      floras. This suggests that the molecular identification of the Canarian endemic
      flora can be achieved as successfully as in other floras where the incidence of
      radiation is not as relevant. The facts that (i) a distance-based criterion was
      unable to discriminate between congeneric and conspecific comparisons and (ii)
      only the character-based discrimination criterion resolved cases that the
      distance-based criterion did not, further support the use of a character
      discrimination approach for a more efficient DNA barcoding of floras from oceanic
      islands like the Canaries. Thus, a barcoding gap seems not to be necessary for
      the correct molecular characterization of the Canarian flora. DNA barcodes also
      suggest the possible existence of cryptic taxa to be further investigated by
      morphology and that the current taxonomic status of some of the taxa analysed may
      need revision. 

PMID- 24919405
TI  - Centrifugal pump performance during low-flow extracorporeal CO2 removal; safety
      considerations.
AB  - AIM: The aim of this study was to examine the hydrodynamic performance and
      gaseous microemboli (GME) activity of two centrifugal pumps for possible use in
      low-flow extracorporeal CO2 removal. MATERIALS & METHODS: The performance of a
      Rotassist 2.8 and a Rotaflow 32 centrifugal pump (Maquet Cardiopulmonary AG,
      Hirrlingen, Germany) was evaluated in a water-glycerine mixture-filled in vitro
      circuit that enabled measurement of pressures and GME at the pump inlet and pump
      outlet. Pressure-flow curves were acquired in a 1,000 to 5,000 rpm range while
      increasing drainage resistance in one series and outlet resistance in another.
      RESULTS: Respective minimum pump inlet and maximum pump outlet pressures were 
      539 mmHg and 754 mmHg for the Rotassist 2.8 and -606 mmHg and 806 mmHg for the
      Rotaflow 32. Maximum standard deviations on pump pressures and flow amounted to
      3.0 mmHg and 0.03 L/min, respectively, regardless of pump type and drainage or
      outlet resistance. The GME at the pump outlet were detectable at pump inlet
      pressures below -156 mmHg at 0.2 L/min and 2,500 rpm for the Rotassist 2.8 and
      below -224 mmHg at 0.9 L/min and 3,000 rpm for the Rotaflow 32. CONCLUSION: Both
      the Rotassist 2.8 and Rotaflow 32 centrifugal pumps show a comparably high
      hydrodynamic stability, but potential GME formation with decreasing pump inlet
      pressures should be taken into account to ensure safe centrifugal pump-based low
      flow extracorporeal CO2 removal.

PMID- 24919406
TI  - Sun protection behaviors among Puerto Rican adults.

PMID- 24919407
TI  - Coarse-grained simulations of an ionic liquid-based capacitor: I. Density, ion
      size, and valency effects.
AB  - We introduce a hierarchy of generic coarse-grained models of ionic liquids of
      increasing complexity. We use them in molecular dynamics simulations to study the
      differential capacitance of a capacitor consisting of an ionic liquid between two
      planar electrodes. The primary goal is to explain the complex dependence of the
      differential capacitance Cd on the electrode potential U in simple terms, e.g. in
      terms of the size and valency of the ions. For this purpose we introduce the
      symmetric model A, which qualitatively reproduces the Cd(U) dependence predicted
      by the mean-field theory but also reveals strong quantitative deviations. We
      further introduce size asymmetry in model A by increasing the cation size. In
      model B we vary the cation valency, keeping the sizes of both ions constant. We
      show that simultaneous increases in size and valency may compensate for each
      other, leading to a Cd(U) very similar to that for the symmetric case. We
      interpret distinct features in Cd(U) on the basis of the density profiles of the
      ions and charge density profiles. We focus on the first two ion layers at the
      electrode, and demonstrate that the polarization of the ionic liquid proceeds
      through replacement of one ion type by the other, in contrast to the simple
      increase in ion concentrations typical for dilute systems. The understanding
      gained for the simple models serves as a reference for interpretation of complex
      effects of ion size, valency and shape. This is carried through in part II (a
      separate article) where we show how the planar shape of ions in model C brings
      new features to the Cd(U) curve and also to the polarization mechanism.

PMID- 24919408
TI  - Variation in inpatient hospital prices and outpatient service quantities drive
      geographic differences in private spending in Texas.
AB  - OBJECTIVE: To measure the contribution of market-level prices, utilization, and
      health risk to medical spending variation among the Blue Cross Blue Shield of
      Texas (BCBSTX) privately insured population and the Texas Medicare population.
      DATA SOURCES: Claims data for all BCBSTX members and publicly available CMS data
      for Texas in 2011. STUDY DESIGN: We used observational data and decomposed
      overall and service-specific spending into health status and health status
      adjusted utilization and input prices and input prices adjusted for the BCBSTX
      and Medicare populations. PRINCIPAL FINDINGS: Variation in overall BCBSTX
      spending across HRRs appeared driven by price variation, whereas utilization
      variation factored more prominently in Medicare. The contribution of price to
      spending variation differed by service category. Price drove inpatient spending
      variation, while utilization drove outpatient and professional spending variation
      in BCBSTX. The context in which negotiations occur may help explain the patterns
      across services. CONCLUSIONS: The conventional wisdom that Medicare does a better
      job of controlling prices and private plans do a better job of controlling volume
      is an oversimplification. BCBSTX does a good job of controlling outpatient and
      professional prices, but not at controlling inpatient prices. Strategies to
      manage the variation in spending may need to differ substantially depending on
      the service and payer.

PMID- 24919409
TI  - Arginase I gene single-nucleotide polymorphism is associated with decreased risk
      of pulmonary hypertension in bronchopulmonary dysplasia.
AB  - AIM: To test the hypothesis that there are single-nucleotide polymorphisms (SNPs)
      in genes of the l-arginine/nitric oxide pathway associated with pulmonary
      hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD). METHODS:
      Neonates with BPD were enrolled (n = 140) and clinical characteristics compared
      between case (BPD + PH) and control (BPD) groups. DNA was isolated from blood
      leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by
      Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine
      transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase.
      SNPs were selected from the National Center for Biotechnology Information
      database for their putative functionality. Calculated minor allele frequencies
      (MAF) of cases and controls were compared using chi2 and logistic regression.
      RESULTS: Of the 140 patients with BPD, 26% had echocardiographic evidence of PH.
      Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p <
      0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases (MAF
      = 0.23) than controls (MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p
      = 0.047) for each copy of the SNP minor allele in arginase I gene in patients
      with BPD. CONCLUSION: Arginase I SNP (rs2781666) may be associated with
      protection against pulmonary hypertension in preterm neonates with BPD.

PMID- 24919410
TI  - 24-hour efficacy of travoprost/timolol BAK-free versus latanoprost/timolol fixed
      combinations in patients insufficiently controlled with latanoprost.
AB  - INTRODUCTION: To compare the 24-h intraocular pressure (IOP) control and
      tolerability of travoprost/timolol benzalkonium chloride (BAK)-free (TTFC) vs.
      latanoprost/timolol fixed combination preserved with BAK (LTFC) in open-angle
      glaucoma patients insufficiently controlled with latanoprost 0.005% monotherapy
      given once in the evening. METHODS: The authors have conducted a prospective,
      observer-masked, active-controlled, cross-over, comparison study. Qualified open
      angle glaucoma patients who demonstrated a latanoprost-treated morning IOP (10:00
      +/- 1 h) greater than 20 mmHg on two separate visits were randomized for 3 months
      to receive either TTFC or LTFC. Patients were then crossed over to the opposite
      treatment for another 3 months. At the end of the latanoprost run-in and after
      each 3-month therapy period patients underwent 24-h IOP monitoring in the
      habitual position using Goldmann applanation tonometry in the sitting position
      during the day (10:00, 14:00, 18:00 and 22:00) and Perkins tonometry in the
      supine position at night (02:00 and 06:00). Selected ocular surface parameters
      were evaluated after each therapy period. RESULTS: Forty-two open-angle glaucoma
      patients completed the study. The mean 24-h baseline IOP on latanoprost was 21.5
      +/- 1.6 mmHg. Both fixed combinations significantly reduced the IOP at each time
      point, for the mean, peak and fluctuation of 24-h IOP compared with latanoprost
      monotherapy (P < 0.01). When the two fixed combinations were compared directly,
      TTFC provided significantly lower mean 24-h IOP (18.9 +/- 2.2 mmHg) vs. LTFC
      (19.3 +/- 2.3 mmHg) (P = 0.004) and significantly lower IOP at 18:00 (18.6 +/-
      2.5 vs. 19.5 +/- 2.7 mmHg for LTFC) (P < 0.001). Further, TTFC demonstrated
      significantly better tear film break-up time (5.15 vs. 4.65 s), corneal stain
      (1.5 vs. 1.8) and Schirmer I test (9.9 vs. 9.2 mm) compared with LTFC after 3
      months of therapy (P < 0.01 for all comparisons). CONCLUSION: The mean 24-h IOP
      lowering of TTFC was statistically more significant compared to LTFC in patients
      insufficiently controlled with latanoprost monotherapy. Measurement of ocular
      surface health and tear film status favored the BAK-free TTFC compared to LTFC.

PMID- 24919411
TI  - Motives for sports participation as predictions of self-reported outcomes after
      anterior cruciate ligament injury of the knee.
AB  - Aim of the study was to access how individual's motives for participation in
      sports impact on self-reported outcomes 2 years after an anterior cruciate
      ligament injury. Based on a longitudinal cohort study, this secondary analysis
      present data from the Knee Anterior Cruciate Ligament, Nonsurgical versus
      Surgical Treatment (KANON) study, a randomized controlled trial. At baseline, 121
      patients recorded in an initial questionnaire that their motives for sports
      participation fell into four categories: achievement, health, social integration,
      or fun and well-being. These four categories were used as variables in the
      analyses. All 121 subjects completed the 2-year follow-up. The largest
      improvement was seen in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
      subscale sports and recreation function, with an effect size of 2.43. KOOS sports
      and recreation function was also the subscale score best predicted by the motives
      for sports participation. Baseline motives achievement and fun and well-being
      predicted worse levels of pain and function 2 years after the injury, even after
      adjusting for age, gender, treatment and baseline scores. Psychological aspects,
      such as motives for participation in sport, can be factors in predicting of
      patient-reported outcomes 2 years after injury. Evaluating motives for sports
      participation may help predict the outcome 2 years after ACL injury. 

PMID- 24919412
TI  - Outer membrane vesicles are vehicles for the delivery of Vibrio tasmaniensis
      virulence factors to oyster immune cells.
AB  - Vibrio tasmaniensis LGP32, a facultative intracellular pathogen of oyster
      haemocytes, was shown here to release outer membrane vesicles (OMVs) both in the
      extracellular milieu and inside haemocytes. Intracellular release of OMVs
      occurred inside phagosomes of intact haemocytes having phagocytosed few vibrios
      as well as in damaged haemocytes containing large vacuoles heavily loaded with
      LGP32. The OMV proteome of LGP32 was shown to be rich in hydrolases (25%)
      including potential virulence factors such as proteases, lipases, phospholipases,
      haemolysins and nucleases. One major caseinase/gelatinase named Vsp for vesicular
      serine protease was found to be specifically secreted through OMVs in which it is
      enclosed. Vsp was shown to participate in the virulence phenotype of LGP32 in
      oyster experimental infections. Finally, OMVs were highly protective against
      antimicrobial peptides, increasing the minimal inhibitory concentration of
      polymyxin B by 16-fold. Protection was conferred by OMV titration of polymyxin B
      but did not depend on the activity of Vsp or another OMV-associated protease.
      Altogether, our results show that OMVs contribute to the pathogenesis of LGP32,
      being able to deliver virulence factors to host immune cells and conferring
      protection against antimicrobial peptides. 

PMID- 24919413
TI  - Dynamics of quinolone resistance in fecal Escherichia coli of finishing pigs
      after ciprofloxacin administration.
AB  - Escherichia coli resistance to quinolones has now become a serious issue in large
      scale pig farms of China. It is necessary to study the dynamics of quinolone
      resistance in fecal Escherichia coli of pigs after antimicrobial administration.
      Here, we present the hypothesis that the emergence of resistance in pigs requires
      drug accumulation for 7 days or more. To test this hypothesis, 26 pigs (90 days
      old, about 30 kg) not fed any antimicrobial after weaning were selected and
      divided into 2 equal groups: the experimental (EP) group and control (CP) group.
      Pigs in the EP group were orally treated daily with 5 mg ciprofloxacin/kg of body
      weight for 30 days, and pigs in the CP group were fed a normal diet. Fresh feces
      were collected at 16 time points from day 0 to day 61. At each time point, ten E.
      coli clones were tested for susceptibility to quinolones and mutations of gyrA
      and parC. The results showed that the minimal inhibitory concentration (MIC) for
      ciprofloxacin increased 16-fold compared with the initial MIC (0.5 ug/ml) after
      ciprofloxacin administration for 3 days and decreased 256-fold compared with the
      initial MIC (0.5 ug/ml) after ciprofloxacin withdrawal for 26 days. GyrA (S83L,
      D87N/ D87Y) and parC (S80I) substitutions were observed in all quinolone
      resistant E. coli (QREC) clones with an MIC >=8 ug/ml. This study provides
      scientific theoretical guidance for the rational use of antimicrobials and the
      control of bacterial resistance. 

PMID- 24919414
TI  - Modulating effects of pycnogenol(r) on oxidative stress and DNA damage induced by
      sepsis in rats.
AB  - The aim of this study was to evaluate the protective effects of Pycnogenol(r)
      (Pyc), a complex plant extract from the bark of French maritime pine, on
      oxidative stress parameters (superoxide dismutase (SOD), and glutathione
      peroxidase (GPx) activities and total glutathione (GSH) and malondialdehyde (MDA)
      levels), an inflammatory cytokine (tumor necrosis factor alpha (TNF-alpha) level)
      and also DNA damage in Wistar albino rats. Rats were treated with 100 mg/kg
      intraperitonally Pyc following the induction of sepsis by cecal ligation and
      puncture. The decreases in MDA levels and increases in GSH levels, and SOD and
      GPx activities were observed in the livers and kidneys of Pyc-treated septic
      rats. Plasma TNF-alpha level was found to be decreased in the Pyc-treated septic
      rats. In the lymphocytes, kidney, and liver tissue cells of the sepsis-induced
      rats, Pyc treatment significantly decreased the DNA damage and oxidative base
      damage using standard alkaline assay and formamidopyrimidine DNA glycosylase
      modified comet assay, respectively. In conclusion, Pyc treatment might have a
      role in the prevention of sepsis-induced oxidative damage not only by decreasing
      DNA damage but also increasing the antioxidant status and DNA repair capacity in
      rats.

PMID- 24919417
TI  - Effect of thickness ratio on load-bearing capacity of bilayered dental ceramics.
AB  - PURPOSE: The aims of this study were to reveal the mechanism of failure of
      bilayered beams and to assess the thickness ratio effect on the load-bearing
      capacity of the bilayered beams. MATERIALS AND METHODS: Both analytical and
      finite element analysis methods were used to analyze the stress distributions of
      bilayered beams subjected to three-point bending test and the residual thermal
      stresses due to coefficient of thermal expansion mismatch. Then, the ideal load
      bearing capacity of the beams as a function of core thickness was evaluated based
      on the mechanical models. Finally, three-point bending tests were performed on
      Cercon Zirconia /IPS e.max Ceram beams to verify the mechanical models. RESULTS:
      The failure load as a function of core thickness was obtained. For the materials
      employed in this study, the thickness ratio did not significantly affect the load
      bearing capacity of bilayered beams when the thickness ratio changed from 1:2 to
      2:1. CONCLUSIONS: The residual thermal stresses in the core layer have slightly
      beneficial effects on the strength of the beams. The first strength theory can be
      used to explain the mechanism of failure, which can be described as the failure
      is interpreted by tensile stress and ultimate strength of the material. Based on
      the relationship between the thickness ratio and load-bearing capacity, the
      core/veneer thickness ratio of the connector of a fixed partial denture could be
      relatively small to about 1:2 to obtain a good appearance.

PMID- 24919416
TI  - What contributes to a good quality of life in early dementia? Awareness and the
      QoL-AD: a cross-sectional study.
AB  - BACKGROUND: Self-report quality of life (QoL) measures for people with dementia
      are widely used as outcome measures in trials of dementia care interventions.
      Depressed mood, relationship quality and neuropsychiatric symptoms predict scores
      on these measures, whereas cognitive impairment and functional abilities
      typically do not. This study examines whether these self-reports are influenced
      by personality and by the person's awareness of his/her impairments. A strong
      negative association between QoL and awareness of deficits would have
      implications for the validity of self-report in this context and for therapeutic
      interventions aiming to increase adjustment and coping. METHODS: Participants
      were 101 individuals with early-stage dementia and their family carers
      participating in the Memory Impairment and Dementia Awareness (MIDAS) Study. QoL
      was assessed using the QoL-AD scale, and awareness was assessed in relation to
      memory, activities of daily living and social functioning. Self-concept,
      conscientiousness, quality of relationship and mood were assessed and a brief
      neuropsychological battery administered. Carers rated their own stress and well
      being and reported on neuropsychiatric symptoms. A series of regression analyses
      predicting QoL-AD were carried out, identifying key variables in each domain of
      assessment to take forward to an overall model. RESULTS: Cognitive impairment was
      not related to QoL. The final model accounted for 57% of the variance in QoL-AD
      scores, with significant contributions from depressed mood, severity of
      irritability shown by the person with dementia, self-concept, quality of
      relationship (rated by the person with dementia) and male gender. The bivariate
      relationships of QoL-AD with awareness of memory function, awareness of
      functional abilities and conscientiousness were mediated by both depressed mood
      and self-concept. CONCLUSIONS: This study reports the most comprehensive approach
      to evaluation of awareness to date. Most of the indices of awareness used are not
      related to self-reported QoL. Discrepancies in evaluative judgements of memory
      function and functional abilities between people with dementia and carers are
      related to QoL, but this relationship is mediated by both depressed mood and self
      concept, which have a much stronger relationship with QoL. The validity of self
      report measures of QoL in people with early stage dementia is supported by these
      results.

PMID- 24919418
TI  - Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon gamma gene
      transfer on interferon gamma-mediated antitumor activity.
AB  - Interferon gamma (IFN-gamma), an anticancer agent, is a strong inducer of
      indoleamine 2,3-dioxygenase 1 (IDO1), which is a tryptophan-metabolizing enzyme
      involved in the induction of tumor immune tolerance. In this study, we
      investigated the IDO1 expression in organs after IFN-gamma gene transfer to mice.
      IFN-gamma gene transfer greatly increased the mRNA expression of IDO1 in many
      tissues with the highest in the liver. This upregulation was associated with
      reduced L-tryptophan levels and increased L-kynurenine levels in serum,
      indicating that IFN-gamma gene transfer increased the IDO activity. Then, Lewis
      lung carcinoma (LLC) tumor-bearing wild-type and IDO1-knockout (IDO1 KO) mice
      were used to investigate the effects of IDO1 on the antitumor activity of IFN
      gamma. IFN-gamma gene transfer significantly retarded the tumor growth in both
      strains without any significant difference in tumor size between the two groups.
      By contrast, the IDO1 activity was increased only in the wild-type mice by IFN
      gamma gene transfer, suggesting that cells other than LLC cells, such as tumor
      stromal cells, are the major contributors of IDO1 expression in LLC tumor. Taken
      together, these results imply that IFN-gamma gene transfer mediated IDO1
      upregulation in cells other than LLC cells has hardly any effect on the antitumor
      activity of IFN-gamma. 

PMID- 24919419
TI  - Lentiviral protein delivery of meganucleases in human cells mediates gene
      targeting and alleviates toxicity.
AB  - Site-specific endonucleases can be engineered for custom recognition of any
      genetic locus and used for gene targeting. Yet, the prolonged expression and
      accumulation of these nucleases in cells lead to toxic effect. Here we describe
      an efficient and quantitative method for introducing nucleases into cells as
      proteins packaged within lentiviral vector particles. I-CreI-derived
      meganucleases, which can be engineered as single-chain proteins, were
      incorporated into lentiviral vector particles either without modification or as
      fusions with cyclophilin A. The small amount of nuclease delivered by the viral
      particles is sufficient to induce efficient targeted mutagenesis in human HEK293H
      and primary T cells. When a repair template sequence was packaged in the
      lentiviral vector, high levels of homologous gene targeting were obtained and
      toxicity was markedly reduced. 

PMID- 24919420
TI  - Asymmetric organocatalytic epoxidations: reactions, scope, mechanisms, and
      applications.
AB  - Chiral epoxides serve as versatile building blocks in the synthesis of complex
      organic frameworks. The high strain imposed by the three-membered ring system
      makes epoxides prone to a variety of nucleophilic ring-opening reactions. Since
      the development of the Sharpless epoxidation, there have been many important
      contributions and advances in this area. With the rapid development of the field
      of asymmetric organocatalysis, a wide range of organocatalysts is now able to
      catalyze the epoxidation of broad class of unsaturated carbonyl compounds. In
      this Minireview, recent progress in the development of organocatalytic asymmetric
      epoxidation methods, the proposed mechanisms of these reactions and their
      applications as intermediates is reported. 

PMID- 24919421
TI  - Synthesis of migrastatin and its macroketone analogue and in vivo FRAP analysis
      of the macroketone on E-cadherin dynamics.
AB  - An efficient and scalable synthesis of a key acyclic intermediate used for the
      preparation of migrastatin and its macroketone analogue is described; Brown
      alkoxyallylation is the key step for this synthesis. The macroketone was prepared
      on 100 mg scale by this route. Treatment of invasive pancreatic cancer cells
      grown on a cell-derived matrix or as subcutaneous tumours in nude mice with the
      macroketone inhibited E-cadherin dynamics in a manner consistent with increased
      cell adhesion and reduced invasive potential. 

PMID- 24919422
TI  - Adsorption of small mono- and poly-alcohols on rutile TiO2: a density functional
      theory study.
AB  - We have studied by means of density functional theory including dispersion
      contributions, the interaction of small chain alcohols with up to four carbons
      and three hydroxyl groups on the TiO2(110) rutile surface with different
      reduction degrees. Adsorption takes place through an acid-base interaction that
      can lead to both molecular and dissociated species. The latter are energetically
      preferred. Bulk reduction does not apport significant change neither in the
      structure nor in the adsorption energies, because the electrons are delocalized
      to a great extent. If vacancies are present at the surface these are the best
      adsorption sites for primary and secondary monoalcohols. Tertiary or poly
      alcohols prefer the Ticus channels, but the reasons for the site preference are
      different. In the case of bulky alcohols, steric hindrance is the main adsorption
      controlling factor, while templating effects of the basic (oxygen) sites on the
      surface are the key parameters to understand the adsorption of poly-alcohols.
      Vicinal polyalcohols behave even in a more complex way, for that they prefer the
      vacancy position only when dissociated, otherwise they stay in the Ticus channel.
      Our results warn about the use of small surrogates to investigate the chemistry
      of large alcohols as the adsorption patterns are not only quantitatively but also
      qualitatively wrong. 

PMID- 24919423
TI  - Bent waveguides for matter-waves: supersymmetric potentials and reflectionless
      geometries.
AB  - Non-zero curvature in a waveguide leads to the appearance of an attractive
      quantum potential which crucially affects the dynamics in matter-wave circuits.
      Using methods of supersymmetric quantum mechanics, pairs of bent waveguides are
      found whose geometry-induced potentials share the same scattering properties. As
      a result, reflectionless waveguides, dual to the straight waveguide, are
      identified. Strictly isospectral waveguides are also found by modulating the
      depth of the trapping potential. Numerical simulations are used to demonstrate
      the efficiency of these approaches in tailoring and controlling curvature-induced
      quantum-mechanical effects. 

PMID- 24919424
TI  - A high-capacity, low-cost layered sodium manganese oxide material as cathode for
      sodium-ion batteries.
AB  - A layered sodium manganese oxide material (NaMn3 O5 ) is introduced as a novel
      cathode materials for sodium-ion batteries. Structural characterizations reveal a
      typical Birnessite structure with lamellar stacking of the synthetic nanosheets.
      Electrochemical tests reveal a particularly large discharge capacity of 219 mAh
      g(-1) in the voltage rang of 1.5-4.7 V vs. Na/Na(+) . With an average potential
      of 2.75 V versus sodium metal, layered NaMn3 O5 exhibits a high energy density of
      602 Wh kg(-1) , and also presents good rate capability. Furthermore, the
      diffusion coefficient of sodium ions in the layered NaMn3 O5 electrode is
      investigated by using the galvanostatic intermittent titration technique. The
      results greatly contribute to the development of room-temperature sodium-ion
      batteries based on earth-abundant elements.

PMID- 24919426
TI  - The European Association of Young Neurologists and Trainees in 2014: the dream of
      a united European neurology enters the limelight.

PMID- 24919425
TI  - Developing an agenda for research about policies to improve access to healthy
      foods in rural communities: a concept mapping study.
AB  - BACKGROUND: Policies that improve access to healthy, affordable foods may improve
      population health and reduce health disparities. In the United States most food
      access policy research focuses on urban communities even though residents of
      rural communities face disproportionately higher risk for nutrition-related
      chronic diseases compared to residents of urban communities. The purpose of this
      study was to (1) identify the factors associated with access to healthy,
      affordable food in rural communities in the United States; and (2) prioritize a
      meaningful and feasible rural food policy research agenda. METHODS: This study
      was conducted by the Rural Food Access Workgroup (RFAWG), a workgroup facilitated
      by the Nutrition and Obesity Policy Research and Evaluation Network. A national
      sample of academic and non-academic researchers, public health and cooperative
      extension practitioners, and other experts who focus on rural food access and
      economic development was invited to complete a concept mapping process that
      included brainstorming the factors that are associated with rural food access,
      sorting and organizing the factors into similar domains, and rating the
      importance of policies and research to address these factors. As a last step,
      RFAWG members convened to interpret the data and establish research
      recommendations. RESULTS: Seventy-five participants in the brainstorming exercise
      represented the following sectors: non-extension research (n = 27), non-extension
      program administration (n = 18), "other" (n = 14), policy advocacy (n = 10), and
      cooperative extension service (n = 6). The brainstorming exercise generated 90
      distinct statements about factors associated with rural food access in the United
      States; these were sorted into 5 clusters. Go Zones were established for the
      factors that were rated highly as both a priority policy target and a priority
      for research. The highest ranked policy and research priorities include
      strategies designed to build economic viability in rural communities, improve
      access to federal food and nutrition assistance programs, improve food retail
      systems, and increase the personal food production capacity of rural residents.
      Respondents also prioritized the development of valid and reliable research
      methodologies to measure variables associated with rural food access.
      CONCLUSIONS: This collaborative, trans-disciplinary, participatory process,
      created a map to guide and prioritize research about polices to improve healthy,
      affordable food access in rural communities.

PMID- 24919427
TI  - In vivo decreased dopamine transporter uptake in corticobasal degeneration
      presenting with primary progressive aphasia without parkinsonism.

PMID- 24919429
TI  - Retraction: The effect of anticoagulant choice on collection of cord blood.
AB  - "The effect of anticoagulant choice on collection of cord blood" by M. Badowski,
      C. Shultz and D.T. Harris. Transfusion. First published online: June 12, 2014.
      The above article, published online on June 12, 2014 on Wiley Online Library
      (wileyonlinelibrary.com), has been withdrawn for legal reasons by agreement
      between the authors, the journal Editor in Chief, Paul M. Ness, MD, the AABB, and
      Wiley Periodicals, Inc. The withdrawal has been agreed due to violation of a
      research agreement between the Cord Blood Registry, which commissioned the
      article, and the authors. REFERENCE: Badowski M, Shultz C and Harris DT. The
      effect of anticoagulant choice on collection of cord blood. Transfusion. 2014.
      doi: 10.1111/trf.12744. First published online: 12 JUN 2014.

PMID- 24919430
TI  - Improving access to preparatory information for children undergoing general
      anaesthesia for tooth extraction and their families: study protocol for a Phase
      III randomized controlled trial.
AB  - BACKGROUND: Children can find anaesthesia induction especially distressing and
      postoperative psychological and physical morbidity are common. Preparation
      programmes for general anaesthesia (GA) are highly effective in reducing this
      distress. A Phase II study has already verified the effectiveness of a prototype
      preoperative GA-coping computer game to help children cope with induction in a
      dental GA setting. The biggest patient users of pediatric GA services in the UK
      are children who need to have teeth removed (estimated to be 100,000 yearly).
      Tooth decay is the most common disease in children worldwide. This study is a
      Phase III randomized controlled trial (RCT) and will evaluate the effectiveness
      of the new internet version of this game. METHODS/DESIGN: The Phase III RCT will
      use a double-blind three-armed design. The clinical trial will recruit up to 210
      children and will compare the web-based game against standard care and another
      non-medical game. At least 53 patients in each group will be required for 90%
      statistical power. Distress will be assessed through an evaluation of the child's
      behaviour during the visit and later parental reports of physical and
      psychological morbidity. The satisfaction of parents and children will be
      measured; the mode of usage of the web-based game will be automatically recorded
      and the impact on the service (for example, recovery time and throughput) will be
      reported.The Phase III study primary outcome will measure: (1) patient
      experience: acceptance of anaesthetic induction, child cooperation and distress,
      reduction of peri- and postoperative morbidity, child and family satisfaction,
      and (2) service improvement: anaesthetic time and improvement in throughput.
      Measures will be administered at baseline, at the time of the GA treatment visit,
      and at 48 hours and one week postoperatively. DISCUSSION: This study aims to
      determine the effectiveness of an online GA-coping game for children and families
      undergoing tooth extraction under GA. TRIAL REGISTRATION: ISRCTN18265148
      (registered 24 November 2013).

PMID- 24919432
TI  - Acne subject preference for pump over tube for dispensing fixed-dose combination
      adapalene 0.1%-benzoyl peroxide 2.5% gel.
AB  - INTRODUCTION: Acne is a chronic inflammatory disease. Key to a patient's success
      on fixed-dose adapalene-benzoyl peroxide (BPO) gel is ensuring adherence. Use of
      a pump system to deliver a pre-measured amount of gel with each pressure enables
      application of a more consistent dose vs. the tube, which should improve
      adherence. In the present study, we evaluate patient preference for two different
      containers for dispensing adapalene-BPO gel. METHODS: In this 15-day, open-label
      study, 300 subjects were asked to treat their acne using fixed-dose adapalene
      0.1%-BPO 2.5% gel dispensed in either a tube or a pump once-daily for up to 7
      days. At week 1, subjects switched to the alternative packaging design for the
      same timeframe. At the end of the treatment period, subjects were asked to
      complete a subject preference survey. RESULTS: Among subjects completing the
      survey (n = 291), 79.0% (n = 230) preferred the pump for dispensing adapalene-BPO
      gel and 21.0% (n = 61) preferred the tube (p < 0.001). The top three
      characteristics of the pump were that it was easy to use (89.0%; n = 259/291),
      clean (73.2%; n = 213/291) and convenient (69.4%; n = 202/291). When asked to
      rate their experience with using the pump, 91.8% (n = 267/291; p < 0.001) of
      subjects reported being satisfied on a self-assessment scale. The majority of
      subjects stated they would tell their doctor about their preference for the pump
      next time adapalene-BPO gel was prescribed (76.6%; n = 223/291; p < 0.001) and
      would prefer the pump if both containers cost the same amount (80.1%; n =
      233/291; p < 0.001). CONCLUSION: Patients prefer using a pump instead of a tube
      to dispense adapalene-BPO gel. This delivery mechanism helps to ensure consistent
      application and thus may improve patient adherence to the prescribed acne
      treatment regimen.

PMID- 24919433
TI  - Cost-effectiveness of elective laparoscopic cholecystectomy versus observation in
      older patients presenting with mild biliary disease.
AB  - Our objective was to determine the probability threshold for recurrent symptoms
      at which elective cholecystectomy compared to observation in older patients with
      symptomatic cholelithiasis is the more effective and cost-effective option. We
      built a decision model of elective cholecystectomy versus observation in patients
      >65 presenting with initial episodes of symptomatic cholelithiasis that did not
      require initial hospitalization or cholecystectomy. Probabilities for subsequent
      hospitalization, emergency cholecystectomy, and perioperative complications were
      based on previously published probabilities from a 5 % national sample of
      Medicare patients. Costs were estimated from Medicare reimbursements and from the
      Healthcare Cost and Utilization Project. Utilities (quality-adjusted life years,
      QALYs) were obtained from established literature estimates. Elective
      cholecystectomy compared to observation in all patients was associated with lower
      effectiveness (-0.10 QALYs) and had an increased cost of $3,422.83 per patient at
      2-year follow-up. Elective cholecystectomy became the more effective option when
      the likelihood for continued symptoms exceeded 45.3 %. Elective cholecystectomy
      was both more effective and less costly when the probability for continued
      symptoms exceeded 82.7 %. An individualized shared decision-making strategy based
      on these data can increase elective cholecystectomy rates in patients at high
      risk for recurrent symptoms and minimize unnecessary cholecystectomy for patients
      unlikely to benefit. 

PMID- 24919434
TI  - Obstructive uropathy and vesicovaginal fistula secondary to a retained sex toy in
      the vagina.
AB  - INTRODUCTION: Vaginal foreign bodies (FBs) are a rare cause of vesicovaginal,
      rectovaginal, or urethrovaginal fistulae. AIM: The aim of this study was to
      describe a rare case of vesicovaginal fistula (VVF) and obstructive uropathy and
      to review the literature. METHODS: A case is presented. A comprehensive review of
      the literature was performed (1948-2013). RESULTS: A 38-year-old woman presenting
      with sepsis, obstructive uropathy, and severe emaciation was found to have a sex
      toy retained in her vagina for 10 years. This had caused a VVF and bilateral
      hydroureteronephrosis. Bilateral nephrostomies were inserted and she underwent
      cystoscopy and examination under anesthesia (EUA) with retrieval of FB. A left
      ureteric stricture was demonstrated. Transabdominal VVF repair with omental flap
      and left ureteric re-implantation was performed. The VVF recurred, which was
      successfully re-repaired transvaginally. Seventy-six full text articles were
      reviewed. There were no previously published cases of VVF following vaginal sex
      toy insertion. There are four cases of obstructive uropathy secondary to a
      vaginal FB in the literature: three pessaries and one plastic cap. There are 44
      cases of VVF secondary to FB: 22 plastic caps (typically from aerosol bottles,
      inserted for masturbation or contraception) and 5 pessaries. At least nine were
      in girls aged <=18 years. Average presentation is 15 months (range 2 months to 35
      years) after FB insertion. Most cases were managed with surgical repair;
      predominantly transvaginal. CONCLUSIONS: This case describes an extremely rare
      but potentially life-threatening case of obstructive uropathy caused by a
      chronically retained sex toy, and adds to the list of potentially rare causes of
      a VVF and obstructive uropathy. We advocate urinary diversion, staged removal of
      FB, upper urinary tract imaging, and EUA with VVF repair and/or ureteric
      reimplantation if required. Transvaginal is the preferred access for FB
      associated VVF repair without concomitant ureteric reimplantation.

PMID- 24919435
TI  - Modulation of microRNAs by ionizing radiation in human gastric cancer.
AB  - Gastric cancer is one of the most common cancers in China. Although surgery is
      the primary therapeutic method, radiotherapy has become an integral part,
      particularly in the early and intermediate stages of gastric cancer. microRNAs
      (miRNAs) are involved in the regulation of diverse cellular processes in response
      to intrinsic and extrinsic stress. A change in miRNA expression profile has been
      identified in various types of tumor cells in response to radiation; however,
      there is no relevant information concerning gastric cancer. In the present study,
      we investigated the miRNA profiles of two clinical gastric cancer samples exposed
      to X-rays using miRNA microarray. We found that 16 miRNAs were downregulated and
      2 miRNAs were upregulated significantly in both irradiated samples when compared
      with the unirradiated samples. Decreases in the levels of miR-300 and miR-642
      expression were confirmed by qRT-PCR in more clinical samples and in cultured
      cell lines. We predicted the targets of the two miRNAs with TargetScan and
      classified all the candidate targets with Gene Ontology, which indicated that
      both miR-300 and miR-642 potentially regulate cellular radiation response by
      modulating apoptosis, cell cycle regulation and DNA damage and repair pathway
      related genes. Cell cycle assay and immunofluorescence assay demonstrated that
      miR-300 regulates radiation-induced G2 cell cycle arrest and DNA damage repair.
      In conclusion, our findings indicate that ionizing radiation modulates the miRNA
      expression profile, and the changes in several specific miRNAs such as miR-300
      have the potential to be used in the treatment, diagnosis and prognosis of
      gastric cancer.

PMID- 24919436
TI  - The association between ethnic identity and condom use among young men in the
      Eastern Cape Province, South Africa.
AB  - This article reports on the association between ethnic identity and condom use
      among Black African men in the rural areas of the Eastern Cape Province, South
      Africa. Individual face-to-face structured interviews were conducted by trained
      community research assistants among 1,656 men who had undergone traditional
      initiation and male circumcision. Logistic regression analyses were used to
      explore the association between two components of ethnic identity (cultural
      affiliation and cultural alienation) and condom use. Overall, 49.2 % of the
      participants reported using condoms consistently and, of these users, 66.4 % used
      them correctly. Logistic regression adjusting for age, employment status,
      education level, and nation of origin showed that participants who expressed high
      as opposed to low cultural affiliation were significantly more likely to use
      condoms consistently and correctly when having sex, especially if they reported
      to have more than one sexual partner. Cultural alienation was negatively related
      with consistent condom use, whereas its association with correct use was unclear.
      The findings of this study suggest that positively emphasizing the ethnic
      identity of African black men may promote condom use. 

PMID- 24919439
TI  - 1,10-Phenanthroline and non-symmetrical 1,3,5-triazine dipicolinamide-based
      ligands for group actinide extraction.
AB  - The synthesis and evaluation of new extractants for spent nuclear fuel
      reprocessing are described. New bitopic ligands constituted of phenanthroline and
      1,3,5-triazine cores functionalized by picolinamide groups were designed.
      Synthetic routes were investigated and optimized to obtain twelve new polyaza
      heterocyclic ligands. In particular, an efficient and versatile methodology was
      developed to access non-symmetric 2-substituted-4,6-di(6-picolin-2-yl)-1,3,5
      triazines from the 1,3,5-triazapentadiene precursor in the presence of anhydride
      reagents. Extraction studies showed the ability of both ligand series to extract
      and separate actinides selectively at different oxidation states (U(VI),
      Np(V,VI), Am(III), Cm(III), and Pu(IV)) from an acidic solution (3 M HNO3).
      Phenanthroline-based ligands show the most promising efficiency for use in the
      group actinide extraction (GANEX) process due to a higher number of donor
      nitrogen atoms and a suitable pre-organization of the dipicolinamide-1,10
      phenanthroline architecture.

PMID- 24919440
TI  - Integrative metabolome and transcriptome profiling reveals discordant glycolysis
      process between osteosarcoma and normal osteoblastic cells.
AB  - BACKGROUND: Osteosarcoma (OS) is the most common primary malignant tumor of bone
      in children and adolescents. However, few biomarkers of diagnostic significance
      have been established. In recent years, high-throughput transcriptomic and
      metabolomic approaches make it possible for studying the levels of thousands of
      biomarkers simultaneously. METHODS: In this study, we integrated two disparate
      transcriptomic and metabolomic datasets to find meaningful biomarkers and then
      used an independent dataset to test the sensibility and specificity of these
      biomarkers. RESULTS: By using integrated two datasets, we discovered that the
      biomarkers involved in the glycolysis pathway are highly enriched, including 4
      genes (ENO1, TPI1, PKG1 and LDHC) and 2 metabolites (lactate and pyruvate). The 4
      genes were significantly down-regulated in OS samples as well as the 2
      metabolites. The mixed metabolites + genes signature also outperformed
      metabolites or genes alone, with recall being 0.813 and F-measure being 0.812.
      And the AUC value of metabolites + genes classifier was 0.825 (compared to 0.58
      for metabolites and 0.821 for genes alone). CONCLUSION: Our findings establish
      that integrated transcriptomic and metabolomic signature can be used to
      distinguish OS malignant with good diagnostic accuracy superior to other methods.

PMID- 24919441
TI  - Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients.
AB  - PURPOSE: NRF2 transcription factor is involved in modulation of various
      antioxidant and metabolic genes and, therefore, may modulate anti-carcinogenic
      potential. Association between polymorphisms of NRF2 and five NRF2-regulated
      genes and urinary bladder cancer (BC) risk was analyzed. METHODS: The study group
      included 244 BC patients, while the control group comprised 365 individuals with
      no evidence of malignancy. Genotyping of GSTM1 (deletion), GSTT1 (deletion),
      GSTA1 -69C/T (rs3957357), GSTP1 Ile105Val (rs1695), SOD2 Ala16Val (rs4880) and
      NRF2 -617C/A (rs6721961) in blood genomic DNA was performed by means of real-time
      PCR assays. The associations between gene polymorphism and BC risk were computed
      by logistic regression. RESULTS: The frequency of GSTA1, GSTP1, SOD2 and NRF2
      genotypes did not differ in both groups. A significantly higher BC risk was
      associated with GSTM1 null genotype after adjusting to age, sex and smoking habit
      (OR 1.85, 95 % CI 1.30-2.62; P = 0.001). GSTT1 null (OR 0.50, 95 % CI 0.31-0.81;
      P = 0.005) and GSTP1 Val105Val (OR 0.52, 95 % CI 0.27-0.98; P = 0.04) genotypes
      were associated with reduced BC risk separately or in combination (OR 0.24, 95 %
      CI 0.11-0.51; P < 0.0001) (P heterogeneity = 0.01). Combined GSTT1 null and SOD2
      with at least one 16Val allele among never smokers encompass reduced BC risk (OR
      0.14, 95 % CI 0.03-0.63; P = 0.01) (P heterogeneity = 0.04). CONCLUSIONS: This
      study supports hypothesis that GSTM1 null genotype may be a moderate BC risk
      factor. The gene-gene and gene-environment interactions associated with combined
      GSTP1/GSTT1 and combined GSTT1/SOD2 genetic polymorphisms along with cigarette
      smoking habit may play a significant role in BC risk modulation.

PMID- 24919442
TI  - Quantitative ultrasound texture analysis of fetal lungs to predict neonatal
      respiratory morbidity.
AB  - OBJECTIVE: To develop and evaluate the performance of a novel method for
      predicting neonatal respiratory morbidity based on quantitative analysis of the
      fetal lung by ultrasound. METHODS: More than 13,000 non-clinical images and 900
      fetal lung images were used to develop a computerized method based on texture
      analysis and machine learning algorithms, trained to predict neonatal respiratory
      morbidity risk on fetal lung ultrasound images. The method, termed 'quantitative
      ultrasound fetal lung maturity analysis' (quantusFLMTM), was then validated
      blindly in 144 neonates, delivered at 28 + 0 to 39 + 0 weeks' gestation. Lung
      ultrasound images in DICOM format were obtained within 48 h of delivery and the
      ability of the software to predict neonatal respiratory morbidity, defined as
      either respiratory distress syndrome or transient tachypnea of the newborn, was
      determined. RESULTS: Mean (SD) gestational age at delivery was 36 + 1 (3 + 3)
      weeks. Among the 144 neonates, there were 29 (20.1%) cases of neonatal
      respiratory morbidity. Quantitative texture analysis predicted neonatal
      respiratory morbidity with a sensitivity, specificity, positive predictive value
      and negative predictive value of 86.2%, 87.0%, 62.5% and 96.2%, respectively.
      CONCLUSIONS: Quantitative ultrasound fetal lung maturity analysis predicted
      neonatal respiratory morbidity with an accuracy comparable to that of current
      tests using amniotic fluid.

PMID- 24919443
TI  - Vision and photoentrainment in fishes: the effects of natural and anthropogenic
      perturbation.
AB  - Vision and photoentrainment in fishes are vital for feeding, avoiding predation,
      spatial orientation, navigation, social communication and the synchronization of
      many homeostatic functions such as activity patterns and sleep. The camera-like
      (image-forming) eyes of fishes are optimized to provide a clear view of their
      preferred ecological niche, while non-visual photoreceptors provide irradiance
      detection that mediates circadian photoentrainment, an endogenous time-keeping
      mechanism (biological clock) to respond to predictable changes in environmental
      conditions. Fish and fisheries are under pressure from both natural and
      anthropogenic perturbation, which in many cases alters the intensity and spectral
      composition of the light environment on which they depend for their survival.
      This review examines the effects of a changing light environment and turbidity on
      the health of fishes within a developmental and ecological context. Understanding
      the sensory environment of fishes is vital to predicting their responses and,
      ultimately, their resilience to environmental change and the potential for
      maintaining sustainable levels of biodiversity. 

PMID- 24919444
TI  - Isolated left ventricular diastolic collapse in pericardial tamponade: an
      uncommon echocardiographic finding.
AB  - A case of circumferential moderate pericardial effusion causing isolated collapse
      of left ventricular cavity on two-dimensional echocardiography is reported.
      Pericardial effusion, mostly of infective etiology, is relatively common in this
      part of the world. When large enough to cause tamponade, collapse of right
      atrium, right ventricle, and uncommonly left atrium can be seen. Left ventricular
      collapse is rare, both due to the larger muscle mass and higher chamber pressure.

PMID- 24919445
TI  - The influence of deprivation on suicide mortality in urban and rural Queensland:
      an ecological analysis.
AB  - PURPOSE: A trend of higher suicide rates in rural and remote areas as well as
      areas with low socioeconomic status has been shown in previous research. Little
      is known whether the influence of social deprivation on suicide differs between
      urban and rural areas. This investigation aims to examine how social deprivation
      influences suicide mortality and to identify which related factors of deprivation
      have a higher potential to reduce suicide risk in urban and rural Queensland,
      Australia. METHODS: Suicide data from 2004 to 2008 were obtained from the
      Queensland Suicide Register. Age-standardized suicide rates (15+ years) and rate
      ratios, with a 95% confidence interval, for 38 Statistical Subdivisions (SSDs) in
      Queensland were calculated. The influence of deprivation-related variables on
      suicide and their rural-urban difference were modelled by log-linear regression
      analyses through backward elimination. RESULTS: Among the 38 SSDs in Queensland,
      eight had a higher suicide risk while eleven had a lower rate. Working-age males
      (15-59 years) had the most pronounced geographic variation in suicide rate. In
      urban areas, suicide rates were positively associated with tenant households in
      public housing, Aboriginal and Torres Strait Islander people, the unemployment
      rate and median individual income, but inversely correlated with younger age and
      households with no internet access. In rural areas, only tenant households in
      public housing and households with no internet access heightened the risk of
      suicide, while a negative association was found for younger and older persons,
      low-skilled workers or labourers, and families with low income and no cars.
      CONCLUSIONS: The extent to which social deprivation contributes to suicide
      mortality varies considerably between rural and urban areas.

PMID- 24919447
TI  - Relationship between the v2PO4/amide III ratio assessed by Raman spectroscopy and
      the calcium content measured by quantitative backscattered electron microscopy in
      healthy human osteonal bone.
AB  - Raman microspectroscopy and quantitative backscattered electron imaging (qBEI) of
      bone are powerful tools to investigate bone material properties. Both methods
      provide information on the degree of bone matrix mineralization. However, a head
      to-head comparison of these outcomes from identical bone areas has not been
      performed to date. In femoral midshaft cross sections of three women, 99 regions
      (20*20 MUm2) were selected inside osteons and interstitial bone covering a wide
      range of matrix mineralization. As the focus of this study was only on regions
      undergoing secondary mineralization, zones exhibiting a distinct gradient in
      mineral content close to the mineralization front were excluded. The same regions
      were measured by both methods. We found a linear correlation (R2=0.75) between
      mineral/matrix as measured by Raman spectroscopy and the wt. %Mineral/(100-wt.
      %Mineral) as obtained by qBEI, in good agreement with theoretical estimations.
      The observed deviations of single values from the linear regression line were
      determined to reflect biological heterogeneities. The data of this study
      demonstrate the good correspondence between Raman and qBEI outcomes in describing
      tissue mineralization. The obtained correlation is likely sensitive to changes in
      bone tissue composition, providing an approach to detect potential deviations
      from normal bone.

PMID- 24919446
TI  - From adversity to psychosis: pathways and mechanisms from specific adversities to
      specific symptoms.
AB  - PURPOSE: Although there is considerable evidence that adversities in childhood
      such as social deprivation, sexual abuse, separation from parents, neglect and
      exposure to deviant parental communication are associated with psychosis in later
      life, most studies have considered broad diagnoses as outcomes. In this review we
      consider evidence for pathways between specific types of adversity and specific
      symptoms of psychosis. METHODS: We present theoretical arguments for expecting
      some degree of specificity (although by no means perfect specificity) between
      different kinds of adversity and different symptoms of psychosis. We review
      studies that have investigated social-environmental risk factors for thought
      disorder, auditory-verbal hallucinations and paranoid delusions, and consider how
      these risk factors may impact on specific psychological and biological
      mechanisms. RESULTS: Communication deviance in parents has been implicated in the
      development of thought disorder in offspring, childhood sexual abuse has been
      particularly implicated in auditory-verbal hallucinations, and attachment
      disrupting events (e.g. neglect, being brought up in an institution) may have
      particular potency for the development of paranoid symptoms. Current research on
      psychological mechanisms underlying these symptoms suggests a number of symptom
      specific mechanisms that may explain these associations. CONCLUSIONS: Few studies
      have considered symptoms, underlying mechanisms and different kinds of adversity
      at the same time. Future research along these lines will have the potential to
      elucidate the mechanisms that lead to severe mental illness, and may have
      considerable clinical implications.

PMID- 24919448
TI  - Spiking cortical model-based nonlocal means method for speckle reduction in
      optical coherence tomography images.
AB  - Optical coherence tomography (OCT) images are usually degraded by significant
      speckle noise, which will strongly hamper their quantitative analysis. However,
      speckle noise reduction in OCT images is particularly challenging because of the
      difficulty in differentiating between noise and the information components of the
      speckle pattern. To address this problem, the spiking cortical model (SCM)-based
      nonlocal means method is presented. The proposed method explores self
      similarities of OCT images based on rotation-invariant features of image patches
      extracted by SCM and then restores the speckled images by averaging the similar
      patches. This method can provide sufficient speckle reduction while preserving
      image details very well due to its effectiveness in finding reliable similar
      patches under high speckle noise contamination. When applied to the retinal OCT
      image, this method provides signal-to-noise ratio improvements of >16  dB with a
      small 5.4% loss of similarity.

PMID- 24919450
TI  - On-chip lithium cells for electrical and structural characterization of single
      nanowire electrodes.
AB  - We present a transmission electron microscopy (TEM)-compatible, hybrid
      nanomachined, on-chip construct for probing the structural and electrical changes
      in individual nanowire electrodes during lithium insertion. We have assembled
      arrays of individual beta-phase manganese dioxide (beta-MnO2) nanowires (NWs),
      which are employed as a model material system, into functional electrochemical
      cells through a combination of bottom-up (dielectrophoresis) and top-down
      (silicon nanomachining) unit processes. The on-chip NWs are electrochemically
      lithiated inside a helium-filled glovebox and their electrical conductivity is
      studied as a function of incremental lithium loading during initial lithiation.
      We observe a dramatic reduction in NW conductivity (on the order of two to three
      orders in magnitude), which is not reversed when the lithium is extracted from
      the nanoelectrode. This conductivity change is attributed to an increase in
      lattice disorder within the material, which is observed from TEM images of the
      lithiated NWs. Furthermore, electron energy loss spectroscopy (EELS) was employed
      to confirm the reduction in valence state of manganese, which occurs due to the
      transformation of MnO2 to LixMnO2. 

PMID- 24919449
TI  - Microscale receiver operating characteristic analysis of micrometastasis
      recognition using activatable fluorescent probes indicates leukocyte imaging as a
      critical factor to enhance accuracy.
AB  - Molecular-targeted probes are emerging with applications for optical biopsy of
      cancer. An underexplored potential clinical use of these probes is to monitor
      residual cancer micrometastases that escape cytoreductive surgery and
      chemotherapy. Here, we show that leukocytes, or white blood cells, residing in
      nontumor tissues--as well as those infiltrating micrometastatic lesions--uptake
      cancer cell-targeted, activatable immunoconjugates nonspecifically, which limits
      the accuracy and resolution of micrometastasis recognition using these probes.
      Receiver operating characteristic analysis of freshly excised tissues from a
      mouse model of peritoneal carcinomatosis suggests that dual-color imaging, adding
      an immunostain for leukocytes, offers promise for enabling accurate recognition
      of single cancer cells. Our results indicate that leukocyte identification
      improves micrometastasis recognition sensitivity and specificity from 92 to 93%-
      for multicellular metastases >20 to 30 MUm in size--to 98 to 99.9% for resolving
      metastases as small as a single cell.

PMID- 24919451
TI  - Speeding up hepatocyte proliferation: how triiodothyronine and beta-catenin join
      forces.

PMID- 24919452
TI  - Higher viral load, higher hepatitis B surface antigen clearance?

PMID- 24919453
TI  - Patterns of physical co-/multi-morbidity among patients with serious mental
      illness: a London borough-based cross-sectional study.
AB  - BACKGROUND: Serious mental illness (SMI) is associated with elevated mortality
      compared to the general population; the majority of this excess is attributable
      to co-occurring common physical health conditions. There may be variation within
      the SMI group in the distribution of physical co/multi-morbidity. This study aims
      to a) compare the pattern of physical co- and multi-morbidity between patients
      with and without SMI within a South London primary care population; and, b) to
      explore socio-demographic and health risk factors associated with excess physical
      morbidity among the SMI group. METHODS: Data were obtained from Lambeth DataNet,
      a database of electronic patient records derived from general practices in the
      London borough of Lambeth. The pattern of 12 co-morbid common physical conditions
      was compared by SMI status. Multivariate ordinal and logistic regression analyses
      were conducted to assess the strength of association between each condition and
      SMI status; adjustments were made for potentially confounding socio-demographic
      characteristics and for potentially mediating health risk factors. RESULTS: While
      SMI patients were more frequently recorded with all 12 physical conditions than
      non-SMI patients, the pattern of co-/multi-morbidity was similar between the two
      groups. Adjustment for socio-demographic characteristics - in particular age and,
      to a lesser extent ethnicity, considerably reduced effect sizes and accounted for
      some of the associations, though several conditions remained strongly associated
      with SMI status. Evidence for mediation by health risk factors, in particular
      BMI, was supported. CONCLUSIONS: SMI patients are at an elevated risk of a range
      of physical health conditions than non-SMI patients but they do not appear to
      experience a different pattern of co-/multimorbidity among those conditions
      considered. Socio-demographic differences between the two groups account for some
      of the excess in morbidity and known health risk factors are likely to mediate
      the association. Further work to examine a wider range of conditions and health
      risk factors would help determine the extent of excess mortality attributable to
      these factors.

PMID- 24919454
TI  - The development and validation of the Comprehensive Inventory of Thriving (CIT)
      and the Brief Inventory of Thriving (BIT).
AB  - In this article we present the development and validation of two new measures of
      psychological well-being: the Comprehensive Inventory of Thriving (CIT) and the
      Brief Inventory of Thriving (BIT). These measures were developed with two
      specific goals in mind: (1) to measure a broad range of psychological well-being
      constructs and represent a holistic view of positive functioning; and (2) to
      predict important health outcomes that are useful for researchers and health
      practitioners. The CIT includes 18 subscales with 54 items in total, covering a
      broad range of well-being components. The BIT has 10 items in total and can serve
      as an indicator of psychological well-being and a brief screening tool of mental
      health. The new measures were evaluated in five samples of a total of 3,191 US
      participants with diverse demographics. The CIT and BIT had excellent
      psychometric properties and exhibited convergent validity with existing measures
      of psychological well-being and discriminant validity with measures of ill-being.
      Both measures contributed over and above existing measures of psychology well
      being in predicting a variety of health outcomes, including self-reported and
      objective health status, physical functioning, and health behaviors. In addition,
      we showed the relative importance of thriving compared to ill-being for health
      outcomes and the benefits of assessing individuals' positive functioning beyond
      ill-being. Potential uses of the new measures are discussed. 

PMID- 24919455
TI  - Are testicular mast cells involved in the regulation of germ cells in man?
AB  - Protease activated receptor-2 (PAR-2) is the receptor for the prototype mast cell
      product tryptase. PAR-2 expression by cells of the human germinal epithelium was
      reported, but the exact cellular sites of testicular expression remained unknown.
      That became of interest, because mast cells, expressing tryptase, were found in
      the walls of seminiferous tubules of patients suffering from sub- and
      infertility. This location suggested that mast cells via tryptase might be able
      to influence PAR-2-expressing cells in the germinal epithelium. To explore these
      points, we used testicular paraffin-embedded sections for immunohistochemistry.
      PAR-2-positive cells were mostly basally located cells of the seminiferous
      epithelium, namely spermatogonia. Some stained for the receptor for GDNF
      (GFRalpha-1), and possibly represent spermatogonial stem cells (SSCs). As true
      human SSCs could not be examined, we turned to TCam-2 seminoma cells, expressing
      PAR-2 and stem cell markers, including GFRalpha-1. TCam-2 cells robustly
      responded to stimulation with a specific PAR-2 agonist (SLIGKV) by increased
      intracellular Ca(2+) levels. Recombinant tryptase and trypsin, but not a control
      peptide (VKGILS) evoked this response, implying functional PAR-2. Video imaging
      and caspase 3/7 assays showed that SLIGKV and tryptase prevented spontaneous
      apoptosis and increased proliferation of TCam-2 cells. The expression of the
      marker of pluripotency OCT3/4 was unchanged upon activation of PAR-2, suggesting
      that the stem cell-like character is not changed. Furthermore, human germ cell
      cancers were examined. A subset of seminoma and carcinoma in situ samples
      expressed PAR-2, indicating that yet unknown subgroups exist. Collectively, the
      descriptive data obtained in human testicular sections, in germ cell cancers and
      the functional results in TCam-2 cells imply a trophic role of mast cell-derived
      tryptase for human germ cells. This may be relevant for subtypes of human germ
      cell cancers, and possibly SSCs. It also raises the possibility that PAR-2
      agonists might be useful for the in vitro propagation of human SSCs. 

PMID- 24919456
TI  - The application of multiple biophysical cues to engineer functional neocartilage
      for treatment of osteoarthritis. Part I: cellular response.
AB  - Osteoarthritis (OA) is a complex disease of the joint for which current
      treatments are unsatisfactory, thus motivating development of tissue engineering
      (TE)-based therapies. To date, TE strategies have had some success, developing
      replacement tissue constructs with biochemical properties approaching that of
      native cartilage. However, poor biomechanical properties and limited
      postimplantation integration with surrounding tissue are major shortcomings that
      need to be addressed. Functional tissue engineering strategies that apply
      physiologically relevant biophysical cues provide a platform to improve TE
      constructs before implantation. In the previous decade, new experimental and
      theoretical findings in cartilage biomechanics and electromechanics have emerged,
      resulting in an increased understanding of the complex interplay of multiple
      biophysical cues in the extracellular matrix of the tissue. The effect of
      biophysical stimulation on cartilage, and the resulting chondrocyte-mediated
      biosynthesis, remodeling, degradation, and repair, has, therefore, been
      extensively explored by the TE community. This article compares and contrasts the
      cellular response of chondrocytes to multiple biophysical stimuli, and may be
      read in conjunction with its companion paper that compares and contrasts the
      subsequent intracellular signal transduction cascades. Mechanical, magnetic, and
      electrical stimuli promote proliferation, differentiation, and maturation of
      chondrocytes within established dose parameters or "biological windows." This
      knowledge will provide a framework for ongoing studies incorporating multiple
      biophysical cues in TE functional neocartilage for treatment of OA. 

PMID- 24919457
TI  - Palladium-catalyzed thiocarbonylation of aryl, vinyl, and benzyl bromides.
AB  - A catalytic protocol for synthesis of thioesters from aryl, vinyl, and benzyl
      bromides as well as benzyl chlorides was developed using only stoichiometric
      amounts of carbon monoxide, produced from a solid CO precursor inside a two
      chamber system. As a catalytic system, the combination of bis(benzonitrile)
      palladium(II) chloride and Xantphos furnished the highest yields of the desired
      compounds, along with the weak base, NaOAc, in anisole at 120  degrees C. The
      choice of catalytic system as well as solvent turned out to be important in order
      to ensure a high chemoselectivity in the reaction. Both electron-rich and
      electron-deficient aryl bromides worked well in this reaction. Addition of 1
      equiv of sodium iodide to the reaction improved the chemoselectivity with the
      electron-deficient aryl bromides. The thiol scope included both aryl and alkyl
      thiols, including 2-mercaptobenzophenones, whereby a thiocarbonylation followed
      by a subsequent McMurry coupling yielded differently substituted benzothiophenes.
      It was demonstrated that the methodology could be applied for (13)C introduction
      into the thiophene ring. 

PMID- 24919458
TI  - 6-Plex microsphere immunoassay with imaging planar array detection for mycotoxins
      in barley.
AB  - Mycotoxins are produced by fungi as secondary metabolites. They often multi
      contaminate food and feed commodities posing a health risk to humans and animals.
      A fast and easy to apply multiplex screening of these commodities could be useful
      to detect multi-contamination. For this, we developed a semi-quantitative 6-plex
      immunoassay using a suspension array of paramagnetic colour-coded microspheres
      combined with imaging planar array detection for the mycotoxins aflatoxin B1,
      ochratoxin A, zearalenone, deoxynivalenol, T2-toxin, HT-2 toxin and fumonisin B1.
      Mycotoxin specific monoclonal antibodies were coupled to different sets of
      microspheres and mycotoxins conjugated to the fluorescent protein R-phycoerythrin
      served as reporter molecules. Competition between free mycotoxins in the sample
      and mixed reporter molecules for antibody binding sites on mixed microspheres
      created a multiplex direct inhibition immunoassay. The reagents were selected for
      no or low cross-interactions between the assays and cross-reactions with
      metabolites and possible masked forms were determined. A within-laboratory
      validation was carried out using blank and spiked barley samples. Furthermore,
      the 6-plex was used to screen available barley, and malted barley, reference
      materials. The validation showed very high inter and intra-day precision for all
      samples with a maximum relative standard deviation value of 10%. The screening
      assay allows easy and rapid multiplex detection of the target mycotoxins in
      barley according to EU legislation. With a cut off factor of 50%, based on the EU
      maximum levels, we were able to screen at 2 MUg kg(-1) for aflatoxin B1, 2.5 MUg
      kg(-1) for ochratoxin A, 625 MUg kg(-1) for deoxynivalenol, 50 MUg kg(-1) for
      zearalenone, 1000 MUg kg(-1) for fumonisin B1 and 25 MUg kg(-1) for T-2 toxin.
      Thanks to the transportable planar array system, the developed 6-plex has
      potential for future on-site testing. Future implementation of this method as a
      pre-screening tool, prior to instrumental analysis, is highly attractive since
      costly LC-MS/MS analysis of samples below the maximum levels can be avoided. 

PMID- 24919461
TI  - Andy Haines: Conspicuous consumption is a pet hate.

PMID- 24919460
TI  - Trastuzumab-containing regimens for metastatic breast cancer.
AB  - BACKGROUND: Patients with breast cancer are classified as having cells that over
      express the human epidermal growth factor receptor 2 (known as HER2-positive) or
      not (HER2-negative). Typically, patients with HER2-positive disease have a worse
      prognosis. Trastuzumab is a selective treatment that targets the HER2 pathway.
      The available evidence supporting trastuzumab regimens mostly relies upon
      surrogate endpoints and, although the efficacy results seem to support its use,
      other uncertainties have been raised about its net benefit in relation to
      transient cardiac toxicity and a long-term increased risk of metastasis to the
      central nervous system. OBJECTIVES: To assess the evidence on the efficacy and
      safety of therapy with trastuzumab (overall) and in relation to the type of co
      administered regimen and the line of treatment, i.e. first-line or beyond
      progression, in women with HER2-positive metastatic breast cancer. SEARCH
      METHODS: We searched the Cochrane Breast Cancer Group's (CBCG) Specialised
      Register and used the search strategy developed by the CBCG to search for
      randomised controlled trials (RCTs) in CENTRAL (2013, Issue 1), MEDLINE, EMBASE,
      BIOSIS, the WHO International Clinical Trials Registry Platform (ICTRP) search
      portal and ClinicalTrials.gov (up to 17 January 2013). SELECTION CRITERIA: RCTs
      comparing the efficacy and safety of trastuzumab alone or in combination with
      chemotherapy, hormonal therapy or targeted agents in women with HER2-positive
      metastatic breast cancer. DATA COLLECTION AND ANALYSIS: We collected data from
      published trials. We used hazard ratios (HRs) for time-to-event outcomes and risk
      ratio (RRs) for binary outcomes. Subgroup analyses included type of regimen
      (taxane-containing, anthracycline-containing, aromatase inhibitor-containing or
      other) and treatment line (first-line, beyond progression). MAIN RESULTS: The
      review found seven trials, involving 1497 patients, which met the criteria to be
      included. The trials were generally of moderate methodological quality; two
      studies have not published their results on overall survival so the presence of
      selective outcome reporting bias cannot be ruled out. None of the studies used
      blinding to treatment allocation, though this is unlikely to have biased the
      results for overall survival. Studies varied in terms of co-administered regimen
      and in terms of treatment line. In four studies, trastuzumab was administered
      with a chemotherapy, such as a taxane-containing, anthracycline-containing or
      capecitabine-containing regimen. Two studies considered postmenopausal women and
      administered trastuzumab with hormone-blocking medications, such as an aromatase
      inhibitor. One study administered trastuzumab in addition to lapatinib. Five
      studies out of seven included women treated with trastuzumab administered until
      progression as first-line treatment and two studies considered trastuzumab beyond
      progression. The combined HRs for overall survival and progression-free survival
      favoured the trastuzumab-containing regimens (HR 0.82, 95% confidence interval
      (CI) 0.71 to 0.94, P = 0.004; and HR 0.61, 95% CI 0.54 to 0.70, P < 0.00001,
      respectively; moderate-quality evidence). Trastuzumab increased the risk of
      congestive heart failure (RR 3.49, 90% CI 1.88 to 6.47, P = 0.0009; moderate
      quality evidence) and left ventricular ejection fraction (LVEF) decline (RR 2.65,
      90% CI 1.48 to 4.74, P = 0.006). For haematological toxicities, such as
      neutropenic fever and anaemia, there was no clear evidence that risks differed
      between groups, while trastuzumab seemed to raise the risk of neutropenia. The
      overall survival improvement was maintained when considering patients treated as
      first-line or patients receiving taxane-based regimens. The progression-free
      survival improvement was maintained when considering patients receiving taxane
      based regimens, and patients treated as first-line or subsequent lines. Few data
      were collected on central nervous system progression. Similarly, few studies
      reported on quality of life and treatment-related deaths. AUTHORS' CONCLUSIONS:
      Trastuzumab improved overall survival and progression-free survival in HER2
      positive women with metastatic breast cancer, but it also increased the risk of
      cardiac toxicities, such as congestive heart failure and LVEF decline. The
      available subgroup analyses are limited by the small number of studies. Studies
      that administered trastuzumab as first-line treatment, or along with a taxane
      based regimen, improved mortality outcomes. The evidence to support the use of
      trastuzumab beyond progression is limited. The recruitment in three out of seven
      studies was stopped early and in three trials more than 50% of patients in the
      control groups were permitted to switch to the trastuzumab arms at progression,
      making it more difficult to understand the real net benefit of
      trastuzumab.Trastuzumab is generally used for women with HER2-positive early
      breast cancer in clinical practice, while women enrolled in most of the trials in
      the metastatic setting were naive to trastuzumab. The effectiveness of
      trastuzumab for women relapsing after adjuvant trastuzumab is therefore still an
      open issue, although it is likely that the majority are being offered it again.

PMID- 24919462
TI  - A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large
      B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors.
AB  - BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after
      aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on
      multiple B-cell neoplasms including DLBCL and is a potential target for
      immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized
      IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma
      activity in a phase I study. METHODS: A phase II study was undertaken to evaluate
      the rate and duration of objective responses and safety of single-agent
      dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory
      DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose
      escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed
      by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of
      objective responses, safety, survival, pharmacokinetics, immunogenicity, and
      exploratory correlative studies. RESULTS: Overall response rate was 9% and
      disease control rate (complete remission + partial remission + stable disease)
      was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache,
      chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was
      deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia
      (13%), or thrombocytopenia (19%) occurred without associated infection or
      bleeding. Reversible ocular events, including conjunctivitis and ocular
      hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc
      gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity.
      CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity
      in unselected patients with relapsed DLBCL. Combination regimens and robust
      methods of patient selection may be necessary for further development. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT00435916.

PMID- 24919463
TI  - Implicit treatment of solvent dispersion forces in protein simulations.
AB  - A model is proposed for the evaluation of dispersive forces in a continuum
      solvent representation for use in large-scale computer simulations. The model
      captures the short- and long-range effects of water-exclusion in conditions of
      partial and anisotropic hydration. The model introduces three parameters, one of
      which represents the degree of hydration (water occupancy) at any point in the
      system, which depends on the solute conformation, and two that represent the
      strength of water-water and water-solute dispersive interactions. The model is
      optimized for proteins, using hydration data of a suboptimally hydrated binding
      site and results from dynamics simulations in explicit water. The model is
      applied to a series of aliphatic-alcohol/protein complexes and a set of binary
      and ternary complexes of various sizes. Implications for weak and ultra-weak
      protein-protein association and for simulation in crowded media are discussed.

PMID- 24919464
TI  - Role of downregulation of galectin-9 in the tumorigenesis of gastric cancer.
AB  - Galectin-9 (Gal-9), a member of the beta-galactoside-binding galectin family,
      plays a role in immune response, apoptosis, cell proliferation and cell death.
      Recent studies have shown that abnormal expression of Gal-9 is involved in
      certain primary cancers. The present study is the first investigation of the role
      of Gal-9 gene expression in clinically diagnosed primary gastric cancer tissues.
      Gal-9 mRNA expression was assessed in 44 clinically diagnosed frozen primary
      cancer tissue samples using quantitative PCR (qPCR). Analysis of the qPCR data
      revealed a significant reduction (>2-fold decreased) of Gal-9 gene expression in
      gastric cancer tissues in 77% (34/44) of patients. In patients with gastric
      cancer, although no statistically significant difference was found between
      adjacent (<2 cm away from the cancer tissue) and normal tissues (>5 cm away from
      the cancer tissue), a >2-fold reduction in Gal-9 expression was observed in the
      adjacent tissues of 34% of the patients. Compared to matched normal or adjacent
      tissues, the gene expression of Gal-9 was significantly decreased in tumor
      tissues (p<0.001). The correlation of Gal-9 expression and clinicopathological
      features in gastric cancer was analyzed according to the TNM classification
      system using AJCC stage grouping. In patients with gastric cancer, clinical
      staging, tumor pathological stage (pT stage), tumor cell differentiation, lymph
      node metastasis and survival rate were found to be associated with Gal-9
      expression. However, no significant association was found between Gal-9
      expression and distant metastasis (p>0.05). No significant difference was found
      between patients of different genders, levels of cell differentiation, distant
      metastasis status or different survival time of patients. Compared to normal
      tissues, >2-fold reduction of Tim-3 expression in gastric cancer tissues occurred
      in 59% of patients, but no correlation was found between Gal-9 and Tim-3 in
      gastric cancer. These results strongly suggest that Gal-9 is involved in
      tumorigenesis of gastric cancer.

PMID- 24919465
TI  - Subchondral insufficiency fractures of the knee: review of imaging findings.
AB  - Subchondral insufficiency fracture of the knee (SIFK) is a potentially
      devastating disorder that may progress rapidly to osteoarthritis with articular
      surface collapse. It should be suspected in the appropriate clinical setting, as
      in early stages it is usually indistinct on initial plain radiographs and
      magnetic resonance imaging is required for a definitive diagnosis. Outcome of
      SIFK depends on several factors, including the initial subchondral fracture size,
      patient BMI, degree of osteopenia, as well as early diagnosis and initial
      treatment. The purpose of this paper is to review the clinical presentation,
      pathophysiology, image findings, complications and outcome of SIFK.

PMID- 24919466
TI  - Image quality and radiation dose of lower extremity CT angiography at 70 kVp on
      an integrated circuit detector dual-source computed tomography.
AB  - BACKGROUND: Despite the well-established requirement for radiation dose reduction
      there are few studies examining the potential for lower extremity CT angiography
      (CTA) at 70 kVp. PURPOSE: To compare the image quality and radiation dose of
      lower extremity CTA at 70 kVp using a dual-source CT system with an integrated
      circuit detector to similar studies at 120 kVp. MATERIAL AND METHODS: A total of
      62 patients underwent lower extremity CTA. Thirty-one patients were examined at
      70 kVp using a second generation dual-source CT with an integrated circuit
      detector (70 kVp group) and 31 patients were evaluated at 120 kVp using a first
      generation dual-source CT (120 kVp group). The attenuation and image noise were
      measured and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were
      calculated. Two radiologists assessed image quality. Radiation dose was compared.
      RESULTS: The mean attenuation of the 70 kVp group was higher than the 120 kVp
      group (575 +/- 149 Hounsfield units [HU] vs. 258 +/- 38 HU, respectively, P <
      0.001) as was SNR (44.0 +/- 22.0 vs 32.7 +/- 13.3, respectively, P = 0.017), CNR
      (39.7 +/- 20.6 vs 26.6 +/- 11.7, respectively, P = 0.003) and the mean image
      quality score (3.7 +/- 0.1 vs. 3.2 +/- 0.3, respectively, P < 0.001). The inter
      observer agreement was good for the 70 kVp group and moderate for the 120 kVp
      group. The dose-length product was lower in the 70 kVp group (264.5 +/- 63.1 mGy
      * cm vs. 412.4 +/- 81.5 mGy * cm, P < 0.001). CONCLUSION: Lower extremity CTA at
      70 kVp allows for lower radiation dose with higher SNR, CNR, and image quality
      when compared with standard 120 kVp.

PMID- 24919467
TI  - Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of
      autoimmune diseases: a population-based cohort study.
AB  - OBJECTIVE: Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane
      glycoprotein that has a costimulatory function in the immune response. DPP4
      inhibitors (DPP4i) are oral glucose-lowering drugs for type 2 diabetes mellitus
      (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and
      other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis,
      multiple sclerosis and inflammatory bowel disease, associated with DPP4i in
      patients with T2DM. METHODS: Using US insurance claims data (2005-2012), we
      conducted a population-based cohort study that included initiators of combination
      therapy with DPP4i (DPP4i plus metformin) and non-DPP4i (non-DPP4i plus
      metformin). RA and other AD were identified with >=2 diagnoses and >=1 dispensing
      for AD-specific immunomodulating drugs or steroids. Composite AD includes RA or
      other AD. Propensity score (PS)-stratified Cox proportional hazards models
      compared the risk of AD in DPP4i initiators versus non-DPP4i, controlling for
      potential confounders. RESULTS: After asymmetric trimming on the PS, 73 928
      patients with T2DM starting DPP4i combination therapy and 163 062 starting non
      DPP4i combination therapy were selected. Risks of incident RA and composite AD
      were lower in the DPP4i group versus non-DPP4i with the PS-stratified HR of 0.66
      (95% CI 0.44 to 0.99) for RA, 0.73 (0.51 to 1.03) for other AD and 0.68 (95% CI
      0.52 to 0.89) for composite AD. CONCLUSIONS: In this large cohort of diabetic
      patients, those initiating DPP4i combination therapy appear to have a decreased
      risk of incident AD including RA compared with those initiating non-DPP4i
      combination therapy. These results may suggest possible pharmacological pathways
      for prevention or treatment of AD.

PMID- 24919468
TI  - Influence of the IL17A locus in giant cell arteritis susceptibility.
AB  - OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the
      inflammatory process occurring in giant cell arteritis (GCA). The aim of the
      present study was to assess whether the IL17A locus influences GCA susceptibility
      and its clinical subphenotypes. METHODS: We carried out a large meta-analysis
      including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls
      from four European populations (Spain, Italy, Germany and Norway). Five IL17A
      polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were
      selected by tagging and genotyped using TaqMan assays. Allelic combination and
      dependency tests were also performed. RESULTS: In the pooled analysis, two of the
      five analysed polymorphisms showed evidence of association with GCA (rs2275913:
      PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)).
      A clear trend of association was also found for the rs4711998 variant (PMH=0.059,
      OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was
      evident by conditional regression analysis. In addition, the haplotype harbouring
      the risk alleles better explained the observed association than the polymorphisms
      independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within
      the IL17A locus show a novel association with GCA. This finding supports the
      relevant role of the Th17 cells in this vasculitis pathophysiology.

PMID- 24919469
TI  - Transgenerational inheritance of ovarian development deficiency induced by
      maternal diethylhexyl phthalate exposure.
AB  - Diethylhexyl phthalate (DEHP) is a widely used industrial additive for increasing
      plastic flexibility. It disrupts the physiological functions of endogenous
      hormones and induces abnormal development of mammals. The objectives of the
      present study were to evaluate the effects of DEHP exposure on ovarian
      development of pregnant mice and whether the effects are inheritable. We found
      that the synthesis of oestradiol in pregnant mice after DEHP exposure was
      significantly decreased, and that the first meiotic progression of female fetal
      germ cells was delayed. Furthermore, the DNA methylation level of Stra8 was
      increased and the expression levels of Stra8 were significantly decreased. An
      accelerated rate of follicle recruitment in F1 mice was responsible for the
      depletion of the primordial-follicle pool. Maternal DEHP exposure also
      significantly accelerated the recruitment of primordial follicles in F2 mice. In
      conclusion, our results indicated that maternal DEHP exposure induced ovarian
      development deficiency, which was transgenerational in mice. 

PMID- 24919470
TI  - Incidence of delayed seizures, delayed cerebral ischemia and poor outcome with
      the use of levetiracetam versus phenytoin after aneurysmal subarachnoid
      hemorrhage.
AB  - Current guidelines recommend against the use of phenytoin following aneurysmal
      subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as
      levetiracetam, acceptable. Our objective was to evaluate the risk of poor
      functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH
      patients treated with levetiracetam versus phenytoin. Medical records of patients
      with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with
      phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome
      measure was poor functional outcome, defined as modified Rankin Scale (mRS) score
      >3 at first recorded follow-up. Secondary outcomes measures included DCI and the
      incidence of delayed seizures. The association between the use of levetiracetam
      and phenytoin and the outcomes of interest was studied using logistic regression.
      Medical records of 564 aSAH patients were reviewed and 259 included in the
      analysis after application of inclusion/exclusion criteria. Phenytoin was used
      exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%)
      patients were switched from phenytoin to levetiracetam. Six (2%) patients had
      delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow
      up. On multivariate analysis, only modified Fisher grade and seizure before
      anticonvulsant administration were associated with DCI while age, Hunt-Hess grade
      and presence of intraparenchymal hematoma were associated with mRS score >3.
      Choice of anticonvulsant was not associated with any of the outcomes of interest.
      There was no difference in the rate of delayed seizures, DCI or poor functional
      outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high
      rate of crossover from phenytoin suggests that levetiracetam may be better
      tolerated.

PMID- 24919471
TI  - Dynamics of electrical double layer formation in room-temperature ionic liquids
      under constant-current charging conditions.
AB  - We report detailed simulation results on the formation dynamics of an electrical
      double layer (EDL) inside an electrochemical cell featuring room-temperature
      ionic liquids (RTILs) enclosed between two planar electrodes. Under relatively
      small charging currents, the evolution of cell potential from molecular dynamics
      (MD) simulations during charging can be suitably predicted by the Landau-Ginzburg
      type continuum model proposed recently (Bazant et al 2011 Phys. Rev. Lett. 106
      046102). Under very large charging currents, the cell potential from MD
      simulations shows pronounced oscillation during the initial stage of charging, a
      feature not captured by the continuum model. Such oscillation originates from the
      sequential growth of the ionic space charge layers near the electrode surface.
      This allows the evolution of EDLs in RTILs with time, an atomistic process
      difficult to visualize experimentally, to be studied by analyzing the cell
      potential under constant-current charging conditions. While the continuum model
      cannot predict the potential oscillation under such far-from-equilibrium charging
      conditions, it can nevertheless qualitatively capture the growth of cell
      potential during the later stage of charging. Improving the continuum model by
      introducing frequency-dependent dielectric constant and density-dependent ion
      diffusion coefficients may help to further extend the applicability of the model.
      The evolution of ion density profiles is also compared between the MD and the
      continuum model, showing good agreement.

PMID- 24919473
TI  - Synthesis of novel lipoamino acid conjugates of sapienic acid and evaluation of
      their cytotoxicity activities.
AB  - Novel lipoamino acids were prepared with the coupling of sapienic acid [(Z)-6
      hexadecenoic acid] with alpha - amino group of amino acids and the resulting N
      sapienoyl amino acids were tested for their cytotoxicity activities against four
      cancer based cell lines. Initially, sapienic acid was synthesized by the Wittig
      coupling of triphenylphosphonium bromide salt of 6-bromohexanoic acid and decanal
      with a Z specific reagent. The prepared sapienic acid was subsequently converted
      to its acid chloride which was further coupled with amino acids by the Schotten
      Baumann reaction to form N-sapienoyl amino acid conjugates. Structural
      characterization of the prepared N-sapienoyl amino acid derivatives was done by
      spectral data (IR, mass spectra and NMR). These lipoamino acid derivatives were
      screened for in vitro cytotoxicity evaluation. Cytotoxicity evaluation against
      four cancer cell lines showed that N-sapienoyl isoleucine was active against
      three cell lines whereas other derivatives either showed activity against only
      one or two cell lines with very moderate activity and two derivatives were
      observed to be inactive against the tested cell lines.

PMID- 24919472
TI  - Is laparoscopic colorectal cancer surgery associated with an increased risk in
      obese patients? A retrospective study from China.
AB  - BACKGROUND: The impact of obesity on surgical outcomes after laparoscopic
      colorectal cancer resection in Chinese patients is still unclear. METHODS: We
      retrospectively reviewed the prospectively collected data from 527 consecutive
      colorectal cancer patients who under went laparoscopic resection from January
      2008 to September 2013. Patients were categorized into three groups: nonobese
      (body mass index (BMI) <25.0 kg/m2), obese I (BMI 25.0 = to 29.9 kg/m2) and obese
      II (BMI >=30.0 kg/m2). Clinical characteristics, surgical outcomes and
      postoperative complications were compared between nonobese, obese I and obese II
      patients. RESULTS: From among the 527 patients, there were 371 patients with in
      the nonobese group, 142 patients in the obese I group and 14 patients in the
      obese II group. The patients were well-matched for age, sex and American Society
      of Anesthesiologists class, except for BMI (P = 0.001). The median operative time
      correlated highly significantly with increasing weight (median: nonobese = 135
      minutes, obese I = 145 minutes, obese II = 162.5 minutes; P = 0.001). There
      appeared to be a slight tendency toward grade III complications (rated according
      to the Clavien-Dindo Classification of Surgical Complications) in the obese II
      group, but this difference was not significant (nonobese = 5.1%, obese I = 3.5%
      and obese II = 14.3%; P = 0.178). None of the grade III complications which
      occurred in the obese II group were wound dehiscences that required a stitch.
      Other aspects, such as estimated blood loss, harvested lymph nodes, operation
      type, pathological results, conversion rate and overall postoperative
      complications, were not statistically significant. CONCLUSION: With sufficient
      experience, laparoscopic colorectal cancer surgery is feasible and safe in obese
      Chinese patients.

PMID- 24919474
TI  - Fermentative production of nervonic acid by Mortierella capitata RD000969.
AB  - A high-nervonic acid (cis-15-tetracosenoic acid, C24:1, n-9)-producing
      filamentous fungus of the Mortierella species was discovered among soil
      filamentous fungi. The filamentous fungal strain -RD000969- was isolated from
      soil collected in Kanagawa Prefecture (Japan) and was found to accumulate
      nervonic acid at a rate of 6.94% of the total cellular fatty acids. The base
      sequences of 28S rDNA D1/D2 and ITS 5.8S rDNA showed 100% homology with
      Mortierella capitata CBS 293.96. In addition to nervonic acid, strain RD000969
      produced a large amount of long-chain monounsaturated fatty acids (C20:1, 12.22%;
      C22:1, 4.07%; C26:1, 5.91%) and a small amount of ultra-long-chain fatty acids
      (C28:1, 0.44%; C30:1, 0.06%; C32:1, trace). In the fungal cells, 98.87% of
      nervonic acid was localized at the sn-1,3 position of triacylglycerol. Nervonic
      acid production was maximum (186.3 mg.L(-1)) when the fungus was cultured in
      potato dextrose (PD) medium containing yeast extract, CaCl2, and MgSO4.7H2O.

PMID- 24919475
TI  - Studies of fatty acid composition, physicochemical and thermal properties, and
      crystallization behavior of mango kernel fats from various Thai varieties.
AB  - Mango kernel fat (MKF) has received attention in recent years due to the
      resemblance between its characteristics and those of cocoa butter (CB). In this
      work, fatty acid (FA) composition, physicochemical and thermal properties and
      crystallization behavior of MKFs obtained from four varieties of Thai mangoes:
      Keaw-Morakot (KM), Keaw-Sawoey (KS), Nam-Dokmai (ND) and Aok-Rong (AR), were
      characterized. The fat content of the mango kernels was 6.40, 5.78, 5.73 and
      7.74% (dry basis) for KM, KS, ND and AR, respectively. The analysis of FA
      composition revealed that all four cultivars had oleic and stearic acids as the
      main FA components with ND and AR exhibiting highest and lowest stearic acid
      content, respectively. ND had the highest slip melting point and solid fat
      content (SFC) followed by KS, KM and AR. All fat samples exhibited high SFC at
      20C and below. They melted slowly as the temperature increased and became
      complete liquids as the temperature approached 35 degrees C. During static
      isothermal crystallization at 20 degrees C, ND displayed the highest Avrami rate
      constant k followed by KS, KM and AR, indicating that the crystallization was
      fastest for ND and slowest for AR. The Avrami exponent n of all samples ranged
      from 0.89 to 1.73. The x-ray diffraction analysis showed that all MKFs
      crystallized into a mixture of pseudo-beta', beta', sub-beta and beta structures
      with beta' being the predominant polymorph. Finally, the crystals of the kernel
      fats from all mango varieties exhibited spherulitic morphology.

PMID- 24919476
TI  - Characteristic odorants from bailingu oyster mushroom (Pleurotus eryngii var.
      tuoliensis) and summer oyster mushroom (Pleurotus cystidiosus).
AB  - In this study, the characteristic odorants of the volatile oils from Pleurotus
      species (P. eryngii var. tuoliensis and P. cystidiosus) were extracted by
      hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS),
      gas chromatography-olfactometry (GC-O), and aroma extract dilution analysis
      (AEDA). A total of 52 and 54 components (P. eryngii var. tuoliensis and P.
      cystidiosus, respectively) were identified, representing about 98.8% and 85.1% of
      the volatile oils, respectively. The main components of the P. eryngii var.
      tuoliensis oil were palmitic acid (82, 38.0%), oleic acid (86, 25.0%) and
      linoleic acid (85, 9.7%). The main components of the P. cystidiosus oil, palmitic
      acid (82, 25.8%), indole (54, 9.1%) and myristic acid (77, 5.3%). Regarding the
      aroma components, 16 and 13 components were identified in the P. eryngii var.
      tuoliensis and P. cystidiosus oils respectively, by the GC-O analyses. The
      results of the sniffing test, odor activity value (OAV) and flavor dilution (FD)
      factor indicate that methional, 1-octen-3-ol and nonanal are the main aroma
      active components of P. eryngii var. tuoliensis oil. On the other hands, dimethyl
      trisulfide and 1-octen-3-ol were estimated as the main aroma-active components of
      the P. cystidiosus oil.

PMID- 24919477
TI  - Analyses of the essential oil from Bunium persicum fruit and its antioxidant
      constituents.
AB  - This study was aimed to analyze and identify the antioxidant constituents of the
      essential oil of Bunium persicum (Apiaceae) fruit. The essential oil was obtained
      by hydrodistillation and analyses by GC-FID and GC-MS. The essential oil was
      tested for antioxidant capacity in DPPH radical scavenging and linoleic acid/beta
      carotene assays. The TLC-bioautography method based on DPPH radical assay and GC
      analyses were carried out to characterize the major antioxidant compounds in the
      essential oil. GC analyses showed the presence of sixteen compounds with p-cymene
      (31.1%), cuminaldehyde (22.2%), and gamma-terpinene (11.4%) as the main
      components in the essential oil. The oil exhibited good radical scavenging [IC50
      (DPPH.) = 4.47 (3.96 - 5.05) mg/mL] and antilipid peroxidation [IC50 (beta
      carotene bleaching) = 0.22 (0.16 - 0.31) mg/mL] activities. The TLC tests
      resulted in identification of cuminaldehyde, p-cymene-7-ol, and cuminyl acetate
      as the main constituents of the active oil fraction.

PMID- 24919478
TI  - Flaxseed hull: Chemical composition and antioxidant activity during development.
AB  - Changes in the chemical composition and antioxidant activity of flaxseed hull
      during maturation were investigated. P129 hull variety was studied at four
      maturation stages (St1, St2, St3, and St4). Significant variation in proximate
      composition and flaxseed hull oil characteristics were observed. A significant
      increase in the carbohydrates content of the hull was observed during
      development. The main methyl esters were linolenic acid (48.95 - 51.52 %), oleic
      acid (20.27-23.41%) and linoleic acid (15.62-17.70%). The highest polyunsaturated
      fatty acids (PUFA) were found to be 67.14 % at the first stage of maturity (St1).
      Flaxseed hull oil was of good quality, containing an abundance of omega-3
      essential fatty acids. The iodine value increased, while the saponification value
      of oil decreased during seed development. The decrease in ascorbic acid content
      was steady. The maximum level of total phenolic acid content (128.3 mg/100 g oil)
      was reached at 7 DAF. The antioxidant activity of oilseed was assessed by means
      of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay. Radical
      scavenging activity for green hull was 52.74% and mature hull was 69.32%.

PMID- 24919479
TI  - Triggered J-aggregation in mixed Langmuir-Blodgett films of amphiphilic
      spiropyran having a methoxy group at the 5' position and an azobenzene
      derivative.
AB  - Here, we describe the formation of J-aggregates triggered by isomerization of an
      azobenzene derivative, N-[p-[(p-dodecylphenylazo)phenyloxy]dodecylpyridinium
      bromide (AzP), in mixed Langmuir-Blodgett (LB) films that contain an amphiphilic
      spiropyran with a methoxy group at the 5' position, MeO-SP1822. Pure LB films of
      MeO-SP1822 consist of multilayer domains embedded in a monolayer. UV irradiation
      of the films causes the isomerization of MeO-SP1822 to its merocyanine form, MeO
      MC1822. Pure LB films of AzP comprise finger-like domains and granular domains.
      Irradiating mixed films of MeO-SP1822 and AzP with alternating UV and visible
      light causes J-aggregation of MeO-MC1822, with the amount of J-aggregates
      reaching a maximum at a 1:1 molar ratio. J-aggregation occurs in flat finger-like
      structures originating in the AzP-rich granular domains that are located on top
      of the MeO-MC1822-rich multilayer domains. J-aggregates are also present under
      the AzP-rich granular domains, though these domains do not serve as nucleation
      sites for the finger-like structures. We propose that granular domains serving as
      nucleation sites are partially buried in the multilayer domains, whereas those
      triggering the J-aggregation of MeO-MC1822 under the granular domains are
      situated on top of the multilayer domains.

PMID- 24919480
TI  - Chemical composition, aroma evaluation, and oxygen radical absorbance capacity of
      volatile oil extracted from Brassica rapa cv. "yukina" used in Japanese
      traditional food.
AB  - The chemical composition of the volatile oil extracted from the aerial parts of
      Brassica rapa cv. "yukina" was analyzed using GC-MS, GC-PFPD, and GC-O. A total
      of 50 compounds were identified. The most prominent constituents were (E)-1,5
      heptadiene (40.27%), 3-methyl-3-butenenitrile (25.97%) and 3-phenylpropanenitrile
      (12.41%). With regard to aroma compounds, 12 compounds were identified by GC-O
      analysis. The main aroma-active compounds were dimethyl tetrasulfide (sulphury
      cabbage, FD = 64), 3-phenylpropanenitrile (nutty, FD = 64), 3-methylindole
      (pungent, FD = 64), and methional (potato, FD = 32). The antioxidant activity of
      the aroma-active compounds of the oil was determined using an oxygen radical
      absorbance capacity (ORAC) assay using fluorescein as the fluorescent probe. The
      ORAC values were found to be 785 +/- 67 trolox equivalents (MUmol TE/g) for B.
      rapa cv. "yukina" oil. The results obtained showed that the volatile oil
      extracted from the aerial parts is a good dietary source of antioxidants.

PMID- 24919481
TI  - Risk for nevus transformation and melanoma proliferation and invasion during
      natalizumab treatment: four years of dermoscopic follow-up with
      immunohistological studies and proliferation and invasion assays.

PMID- 24919482
TI  - Carotid-femoral pulse wave velocity is negatively correlated with aortic
      diameter.
AB  - Cardiovascular events pose significant morbidity and mortality burden to
      abdominal aortic aneurysm (AAA) patients. Arterial stiffness as measured by pulse
      wave velocity (PWV) is an independent predictor of cardiovascular risk. We
      investigated the relationship between aortic diameter and PWV. Consecutive
      patients with AAA were invited to participate. Patients completed a health
      questionnaire, received aortic ultrasound and carotid-femoral PWV (cfPWV)
      recordings with a Vicorder. Thirty patients were used for reproducibility
      assessment. A linear regression model was used to identify significant predictors
      of cfPWV. Observer variation was assessed using Bland and Altman analysis and the
      intraclass correlation coefficient. Three hundred and nine patients were included
      148 with AAA and 161 controls. The mean difference for repeated cfPWV between
      observers was 0.11 ms(-1). cfPWV was positively correlated with age (r=0.24,
      P<0.001) and systolic blood pressure (r=0.29, P<0.001) and negatively correlated
      with aortic diameter (r=-0.15, P=0.008). There was no difference in cfPWV between
      AAA and control groups (9.75+/-2.3 ms(-1) vs. 9.55+/-2.3 ms(-1), P=0.43). Aortic
      diameter (P=0.003) and systolic blood pressure (P<0.001) were significant
      predictors of cfPWV independent of age, aspirin usage and a history of myocardial
      infarction. Patients with large AAA (>5 cm) had decreased cfPWV compared with
      patients with small AAA (P=0.02) or normal diameter aorta (P=0.02). Vicorder
      measurements of cfPWV are repeatable. cfPWV is negatively associated with infra
      renal aortic diameter and reduced in large AAA. cfPWV is likely invalid for
      accurate arterial stiffness assessment in patients with AAA owing to the apparent
      confounding effect of aortic size. 

PMID- 24919483
TI  - Spreading of triboelectrically charged granular matter.
AB  - We report on the spreading of triboelectrically charged glass particles on an
      oppositely charged surface of a plastic cylindrical container in the presence of
      a constant mechanical agitation. The particles spread via sticking, as a
      monolayer on the cylinder's surface. Continued agitation initiates a sequence of
      instabilities of this monolayer, which first forms periodic wavy-stripe-shaped
      transverse density modulation in the monolayer and then ejects narrow and long
      particle-jets from the tips of these stripes. These jets finally coalesce
      laterally to form a homogeneous spreading front that is layered along the
      spreading direction. These remarkable growth patterns are related to a time
      evolving frictional drag between the moving charged glass particles and the
      countercharges on the plastic container. The results provide insight into the
      multiscale time-dependent tribolelectric processes and motivates further
      investigation into the microscopic causes of these macroscopic dynamical
      instabilities and spatial structures. 

PMID- 24919484
TI  - Optimizing data collection for public health decisions: a data mining approach.
AB  - BACKGROUND: Collecting data can be cumbersome and expensive. Lack of relevant,
      accurate and timely data for research to inform policy may negatively impact
      public health. The aim of this study was to test if the careful removal of items
      from two community nutrition surveys guided by a data mining technique called
      feature selection, can (a) identify a reduced dataset, while (b) not damaging the
      signal inside that data. METHODS: The Nutrition Environment Measures Surveys for
      stores (NEMS-S) and restaurants (NEMS-R) were completed on 885 retail food
      outlets in two counties in West Virginia between May and November of 2011. A
      reduced dataset was identified for each outlet type using feature selection.
      Coefficients from linear regression modeling were used to weight items in the
      reduced datasets. Weighted item values were summed with the error term to compute
      reduced item survey scores. Scores produced by the full survey were compared to
      the reduced item scores using a Wilcoxon rank-sum test. RESULTS: Feature
      selection identified 9 store and 16 restaurant survey items as significant
      predictors of the score produced from the full survey. The linear regression
      models built from the reduced feature sets had R2 values of 92% and 94% for
      restaurant and grocery store data, respectively. CONCLUSIONS: While there are
      many potentially important variables in any domain, the most useful set may only
      be a small subset. The use of feature selection in the initial phase of data
      collection to identify the most influential variables may be a useful tool to
      greatly reduce the amount of data needed thereby reducing cost.

PMID- 24919485
TI  - Cluster randomized trials utilizing primary care electronic health records:
      methodological issues in design, conduct, and analysis (eCRT Study).
AB  - BACKGROUND: There is growing interest in conducting clinical and cluster
      randomized trials through electronic health records. This paper reports on the
      methodological issues identified during the implementation of two cluster
      randomized trials using the electronic health records of the Clinical Practice
      Research Datalink (CPRD). METHODS: Two trials were completed in primary care: one
      aimed to reduce inappropriate antibiotic prescribing for acute respiratory
      infection; the other aimed to increase physician adherence with secondary
      prevention interventions after first stroke. The paper draws on documentary
      records and trial datasets to report on the methodological experience with
      respect to research ethics and research governance approval, general practice
      recruitment and allocation, sample size calculation and power, intervention
      implementation, and trial analysis. RESULTS: We obtained research governance
      approvals from more than 150 primary care organizations in England, Wales, and
      Scotland. There were 104 CPRD general practices recruited to the antibiotic trial
      and 106 to the stroke trial, with the target number of practices being recruited
      within six months. Interventions were installed into practice information systems
      remotely over the internet. The mean number of participants per practice was
      5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient
      of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures
      showed substantial correlations between the 12 months before, and after
      intervention, with coefficients ranging from 0.42 for diastolic blood pressure to
      0.91 for proportion of consultations with antibiotics prescribed, defining
      practice and participant eligibility for analysis requires careful consideration.
      CONCLUSIONS: Cluster randomized trials may be performed efficiently in large
      samples from UK general practices using the electronic health records of a
      primary care database. The geographical dispersal of trial sites presents a
      difficulty for research governance approval and intervention implementation.
      Pretrial data analyses should inform trial design and analysis plans. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both
      registered on 17 March 2010).

PMID- 24919488
TI  - Schizophrenia: no health without physical health.

PMID- 24919486
TI  - Fully automated high-throughput chromatin immunoprecipitation for ChIP-seq:
      identifying ChIP-quality p300 monoclonal antibodies.
AB  - Chromatin immunoprecipitation coupled with DNA sequencing (ChIP-seq) is the major
      contemporary method for mapping in vivo protein-DNA interactions in the genome.
      It identifies sites of transcription factor, cofactor and RNA polymerase
      occupancy, as well as the distribution of histone marks. Consortia such as the
      ENCyclopedia Of DNA Elements (ENCODE) have produced large datasets using manual
      protocols. However, future measurements of hundreds of additional factors in many
      cell types and physiological states call for higher throughput and consistency
      afforded by automation. Such automation advances, when provided by multiuser
      facilities, could also improve the quality and efficiency of individual small
      scale projects. The immunoprecipitation process has become rate-limiting, and is
      a source of substantial variability when performed manually. Here we report a
      fully automated robotic ChIP (R-ChIP) pipeline that allows up to 96 reactions. A
      second bottleneck is the dearth of renewable ChIP-validated immune reagents,
      which do not yet exist for most mammalian transcription factors. We used R-ChIP
      to screen new mouse monoclonal antibodies raised against p300, a histone
      acetylase, well-known as a marker of active enhancers, for which ChIP-competent
      monoclonal reagents have been lacking. We identified, validated for ChIP-seq, and
      made publicly available a monoclonal reagent called ENCITp300-1. 

PMID- 24919489
TI  - Use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS
      TBNA) in the diagnosis of granulomatous mediastinal lymphadenopathy.
AB  - INTRODUCTION: This study assessed the clinical utility of endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis
      of suspected granulomatous mediastinal lymphadenopathy. MATERIALS AND METHODS:
      Retrospective chart review of all patients who underwent EBUS-TBNA for suspected
      granulomatous mediastinal lymphadenopathy at Singapore General Hospital between
      December 2008 and December 2011 inclusive. RESULTS: Over a period of 3 years, a
      total of 371 patients underwent EBUS-TBNA of whom 33 (9%) had the procedure
      performed for evaluation of suspected granulomatous mediastinal lymphadenopathy -
      18 for suspected tuberculosis (TB) and non-tuberculous mycobacterial (NTM)
      lymphadenitis, and 15 for suspected sarcoidosis. EBUS-TBNA was diagnostic in 9 of
      the 13 patients with a final diagnosis of TB/NTM. EBUS-TBNA cultures were
      positive in 6 of them (46%), 1 showed acid-fast bacilli (AFB) although cultures
      were negative, and 2 had necrotising granulomatous inflammation from EBUS-TBNA
      biopsies and sputum cultures grew TB. EBUS-TBNA was diagnostic in 9 of the 14
      patients with a final diagnosis of sarcoidosis through histology showing non
      caseating granulomatous inflammation. The sensitivities of EBUS-TBNA for
      diagnosis of TB/NTM, sarcoidosis and overall granulomatous mediastinal
      lymphadenopathy were 69%, 64%, 64%; the negative predictive values were 56%, 17%,
      33%; and accuracies were 78%, 67%, 70%, respectively. CONCLUSION: EBUS-TBNA can
      be useful in the diagnosis of suspected granulomatous mediastinal lymphadenopathy
      with sensitivities and accuracies of >60%.

PMID- 24919490
TI  - Systemic Candidiasis in Extremely Low Birthweight (ELBW) Neonates Despite the
      Routine Use of Topical Miconazole Prophylaxis: Trends, Risk Factors and Outcomes
      over an 11-Year Period.
AB  - INTRODUCTION: This study aims to determine the incidence, trends of systemic
      candidiasis and meningitis in extremely low birthweight (ELBW) neonates (<1000
      gms) despite the routine use of topical miconazole prophylaxis and to compare the
      risk factors, adverse outcomes and comorbidities with controls. MATERIALS AND
      METHODS: Retrospective cohort study of ELBW neonates with systemic candidiasis
      and meningitis over an 11-year period (1997 to 2007). Matched case control
      analyses were performed to determine the risk factors and comorbidities which
      were severe intraventricular haemorrhage (IVH), severe retinopathy of prematurity
      (ROP), patent ductus arteriosus (PDA) requiring treatment, necrotising
      enterocolitis (NEC), chronic lung disease (CLD) and cholestatic jaundice.
      Mortality and end organ involvement secondary to systemic candidiasis were
      identified as adverse outcomes. RESULTS: Of the 757 ELBW neonates, 51 (6.7%) had
      evidence of systemic candidiasis with a significant 3-fold increase in trend
      noted in 2007 as compared against 1997 (12.1% vs 3.8%) (RR 1.2, 95% CI, 1.06 to
      1.36, P <0.001). This corresponds to a significant increasing trend of preceding
      or co-existent bacterial blood stream infections (BSI) in neonates with systemic
      candidiasis (0% in 1997 vs 7.1% in 2007, RR 1.40, 95% CI, 1.04 to 1.25, P =
      0.005). On logistic regression analysis, decreasing gestational age was an
      independent risk factor for systemic candidiasis (OR 2.0, 95% CI, 1.52 to 2.63, P
      <0.001). Candida meningitis was detected in 4/38 (10.5%) and end organ
      involvement in 17 (33%). The organisms isolated were Candida parapsilosis 31
      (61%), Candida albicans 17 (33%) and Candida glabrata 3 (5.8%). Significantly
      higher mortality was seen in cases when compared to controls 10/51 (19.6%) vs
      76/706 (10.7%) (OR 2.02, 95% CI, 1.02 to 4.40, P <0.001). CONCLUSION: Increasing
      trend in the incidence of systemic candidiasis despite routine use of topical
      miconazole prophylaxis is of concern and future studies comparing the use of
      systemic fl uconazole versus oral nystatin may need to be considered.

PMID- 24919491
TI  - The Looi suture technique for anchoring the lateral tarsal strip to the lateral
      orbital wall.
AB  - INTRODUCTION: The lateral tarsal strip procedure (LTS) was first reported by
      Anderson and Gordy in 1979 for the management of paralytic or senile eyelid
      laxity. Since its description, the LTS procedure has been subject to several
      modifications by various authors. In this study, we described the Looi suture
      technique, a small modification in the technique of suturing the LTS to the
      lateral orbital wall periosteum. Using this technique, the surgeon achieves a
      larger area of contact between the anterior surface of the tarsal strip and the
      lateral orbital wall periosteum, promoting a stronger adhesion. With a double
      armed suture, the technique also allows for adjustment of the lower lid tension
      to avoid over- or under-correction of horizontal lid laxity. This study aimed to
      evaluate the technique. MATERIALS AND METHODS: This was a retrospective non
      comparative case series of 39 eyelids of 31 patients who underwent LTS with Looi
      suturing technique for the correction of involutional lower lid laxity which had
      resulted in either entropion or ectropion. In this procedure, a novel technique
      utilising a double armed 5/0 Ethibond suture is used to secure the LTS to the
      lateral orbital rim, with the aim of increasing appositional contact between the
      LTS and periosteum. RESULTS: In 36 eyelids with entropion, the procedure was
      combined with lower lid retractor repair, and in 3 eyelids with ectropion, with
      medial tarsoconjunctivoplasty. Surgery was successful in 37 of 39 eyelids
      (94.87%) after one procedure. The remaining 2 eyelids required repeat procedures
      to achieve anatomical success. Both cases had been performed by trainee surgeons
      under supervision. Postoperative follow-up period ranged from 1 day (in a
      visiting overseas patient) to 2 years. CONCLUSION: This study described the Looi
      suturing technique in performing the LTS procedure and we found it a simple and
      effective modification when dealing with lower lid laxity.

PMID- 24919492
TI  - The golden hours in paediatric septic shock--current updates and recommendations.
AB  - INTRODUCTION: Paediatric sepsis is a global health problem. It is the leading
      cause of mortality in infants and children worldwide. Appropriate and timely
      initial management in the first hours, often termed as the "golden hours", has
      great impact on survival. The aim of this paper is to summarise the current
      literature and updates on the initial management of paediatric sepsis. MATERIALS
      AND METHODS: A comprehensive literature search was performed via PubMed using the
      search terms: 'sepsis', 'septic shock', 'paediatric' and 'early goal-directed
      therapy'. Original and review articles were identified and selected based on
      relevance to this review. RESULTS: Early recognition, prompt fluid resuscitation
      and timely administration of antibiotics remain key in the resuscitation of the
      septic child. Use of steroids and tight glycaemic control in this setting remain
      controversial. CONCLUSION: The use of early goal-directed therapy has had
      significant impact on patient outcomes and protocolised resuscitation of children
      in septic shock is recommended.

PMID- 24919493
TI  - Anticoagulation needs in asians with atrial fibrillation: a mythbuster.
AB  - Atrial fibrillation (AF) has long been known to increase the risk of stroke. As a
      result, relevant international guidelines recommend that measures to reduce the
      risk of thrombus formation should be considered in all patients presenting with
      AF. Based on risk assessment scores, patients would then receive either
      thrombocyte aggregation inhibitors or oral anticoagulants. Despite this advice,
      compliance rates with the recommendations are poor across all countries surveyed.
      Evidence from the Global Anticoagulant Registry in the Field (GARFIELD) registry
      shows that major deviation from guidelines is due in large part to physicians'
      decision-making. In this brief narrative review, we address some of the frequent
      reasons cited by physicians why the guidelines are disregarded for Asian
      patients.

PMID- 24919494
TI  - Combined transcatheter therapy of aortic stenosis and thoracic aortic aneurysm.

PMID- 24919495
TI  - Obstructed Hemivagina and Ipsilateral Renal Anomaly--A Reproductive Surgical
      Unit's Experience.

PMID- 24919496
TI  - Prostate carcinoma presenting with symptoms mimicking rectal cancer.

PMID- 24919497
TI  - General Surgery (GS) Residency Selection Process: A Comparison Between Singapore
      (Singhealth) and United States.

PMID- 24919498
TI  - Re: General Surgery (GS) Residency Selection Process: A Comparison Between
      Singapore (Singhealth) and United States.

PMID- 24919500
TI  - The challenge of segmental small bowel motility quantitation using MR
      enterography.
AB  - OBJECTIVE: Analysis of "cine" MRI using segmental regions of interest (ROIs) has
      become increasingly popular for investigating bowel motility; however, variation
      in motility in healthy subjects both within and between scans remains poorly
      described. METHODS: 20 healthy individuals (mean age, 28 years; 14, males)
      underwent MR enterography to acquire dynamic motility scans in both breath hold
      (BH) and free breathing (FB) on 2 occasions. Motility data were quantitatively
      assessed by placing four ROIs per subject in different small bowel segments and
      applying two measures: (1) contractions per minute (CPM) and (2) Jacobian
      standard deviation (SD) motility score. Within-scan (between segment) variation
      was assessed using intraclass correlation (ICC), and repeatability was assessed
      using Bland-Altman limits of agreement (BA LoA). RESULTS: Within-scan segmental
      variation: BH CPM and Jacobian SD metrics between the four segments demonstrated
      ICC R = 0.06, p = 0.100 and R = 0.20, p = 0.027 and in FB, the CPM and Jacobian
      SD metrics demonstrated ICC R = -0.26, p = 0.050 and R = 0.19, p = 0.030.
      Repeatability: BH CPM for matched segments ranged between 0 and 14 contractions
      with BA LoA of +/-8.36 and Jacobian SD ranged between 0.09 and 0.51 with LoA of
      +/-0.33. In FB data, CPM ranged between 0 and 10 contractions with BA LoA of +/
      7.25 and Jacobian SD ranged between 0.16 and 0.63 with LoA = +/-0.28. CONCLUSION:
      The MRI-quantified small bowel motility in normal subjects demonstrates wide
      intersegmental variation and relatively poor repeatability over time. ADVANCES IN
      KNOWLEDGE: This article presents baseline values for healthy individuals of
      within- and between-scan motility that are essential for understanding how this
      process changes in disease.

PMID- 24919501
TI  - The complete mitochondrial genome of Sitobion avenae (Hemiptera: Aphididae).
AB  - In this paper, we sequenced the complete mitogenome of the English grain aphid,
      Sitobion avenae. The mitogenome was mainly consisted of 13 protein-coding genes,
      22 tRNA genes, 2 rRNA genes, and 2 large noncoding regions. The 15,180-bp
      mitogenome with a high A + T content (84.22%) was arranged in the same gene order
      as that of the ancestral insect. The repeat region between trnE and trnF included
      1.29 copies of a 202 bp repeat unit. Characterization of the S. avenae mitogenome
      revealed architecture of one of important worldwide agricultural pests, thus
      advancing our understanding of insect mitogenomic diversities and further
      utilization in phylogenetic analysis. 

PMID- 24919499
TI  - Liver in the analysis of body composition by dual-energy X-ray absorptiometry.
AB  - OBJECTIVE: To investigate the predictive value for hepatic steatosis of a new
      software for the quantification of visceral fat by dual-energy X-ray
      absorptiometry (DXA) and to design new regions of interest (ROIs). METHODS: Adult
      volunteers were prospectively screened for hepatic steatosis by ultrasonography
      to obtain a well-balanced population according to the presence/absence of the
      disease. 90 adult patients without steatosis and 90 with steatosis (mild, 53.3%;
      moderate, 37.7%; and severe, 10.0%) were recruited. On the same day, all subjects
      were submitted to blood testing and to anthropometric and whole-body DXA for body
      composition evaluation. A new software for android visceral fat assessment was
      employed, and six new "liver-suited" ROIs as well as two modified android ROIs
      were designed. Their association with steatosis grade was tested by correlation
      analysis. RESULTS: Fat mass (FM) of the new ROIs showed the highest correlation
      coefficients with steatosis grade (rho = 0.610-0.619; p < 0.001), which was also
      confirmed by multivariate analysis. On the whole population, the new ROIs
      maintained the highest predictive role for liver steatosis, with areas under the
      receiver operating characteristic curve up to 0.820 +/- 0.032. Inter- and intra
      operator agreement for the new ROIs was excellent (k = 0.915-1.000 and k = 0.927
      1.000). CONCLUSION: New ROIs could be designed, standardized and implemented in
      DXA whole-body scan to provide more specific and predictive values of hepatic
      lipid content. ADVANCES IN KNOWLEDGE: This is the first study to investigate the
      predictive value for hepatic steatosis of visceral and regional FM assessed on
      the hepatic site by DXA in comparison with ultrasonography, anthropometry and
      surrogate markers derived by previously validated algorithms (fatty liver index).

PMID- 24919502
TI  - Complete mitochondrial genome of Rhipicephalus simus.
AB  - In this study, we report the basic characteristics of the Rhipicephalus simus
      mitochondrial genome, including structural organization and base composition of
      the rRNAs, tRNAs and protein-coding genes. The total length of the mitogenome was
      14,929 bp, included 37 genes and with a genome structure similar to other ticks. 

PMID- 24919503
TI  - Complete mitochondrial DNA sequencing of Vieja synspila, a cichlid fish.
AB  - The Redhead cichlid (Vieja synspila) is an important aquarium fish and a useful
      phylogenetic organism of the Cichlidae family. In this study, we sequenced the
      mitochondrial genome of the Redhead cichlid for the first time. The mitogenome
      (16,543 bp) had the typical mitochondrial characteristics of other cichlid fish,
      including 13 protein-coding, 22 tRNA, two rRNA genes and one putative control
      region. This sequence will be helpful in studying the phylogenetic relationships
      between cichlid fish.

PMID- 24919504
TI  - Complete mitochondrial genomes of the Northern (Salvelinus malma) and Southern
      (Salvelinus curilus) Dolly Varden chars (Salmoniformes, Salmonidae).
AB  - The complete mitochondrial genomes were sequenced from the Northern and Southern
      Dolly Varden chars, Salvelinus malma and S. curilus. The genome sequences are
      16,654 bp in size in both species, and the gene arrangement, composition, and
      size are very similar to the salmonid fish genomes published previously. The
      level of sequence divergence between S. malma and S. curilus inferred from the
      complete mitochondrial genomes is relatively low (1.88%) indicating recent
      divergence of the species and/or historical hybridization. 

PMID- 24919505
TI  - Characterization of the mitochondrial genome of the cabbage webworm, Hellula
      undalis (Lepidoptera: Pyralidae).
AB  - The sequenced mitochondrial genome of the cabbage webworm Hellula undalis
      includes 13 protein-coding genes (PCGs) (nad1-6, cox1-3, atp6, atp8, nad4L and
      cob), two ribosomal RNAs (12S and 16S) and 19 transfer RNAs, which is 14,678 bp
      in length. Its gene order and orientation are identical to the common types found
      in most of the other completely sequenced lepidopteran mitogenomes. Thirteen PCGs
      start with a typical ATN codon, while cox1 uses CGA as its start codon. Some PCGs
      use the standard TAA as their termination codon, while others use the incomplete
      termination codon T (cox1, cox2 and nad4). 

PMID- 24919506
TI  - The complete mitochondrial genome sequence of Triplophysa anterodorsalis
      (Teleostei, Balitoridae, Nemacheilinae).
AB  - Triplophysa anterodorsalis is an endemic fish in the upper stream of the Yangtze
      River, Jinsha River and its tributaries. However, wild populations of T.
      anterodorsalis declined sharply due to cascade hydropower stations constructed
      successively in the Jinsha River during the past decades. In the present study,
      the complete mitochondrial DNA genome sequence of T. anterodorsalis was first
      determined by DNA sequencing based on the PCR fragments. The complete
      mitochondrial genome sequence of T. anterodorsalis is a circular molecule of
      16,567 bp in size. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA
      genes, and a control region (D-loop). The gene nucleotide composition of T.
      anterodorsalis is 27.37% A, 25.68% C, 18.37% G, and 28.57% T, with a relatively a
      relatively high A + T content (55.94%). The results could provide useful data for
      studies on genetic structure and diversity and rational resource conservation in
      T. anterodorsalis. 

PMID- 24919508
TI  - Development and in-vivo evaluation of ondansetron gels for transdermal delivery.
AB  - Nausea and vomiting are some of the major side effects caused by certain drug
      therapies, e.g. chemotherapy, radiotherapy and general anesthesia. Because of the
      nature of the symptoms, oral delivery is inappropriate, while intravenous
      administration may be unpractical. The aim of the present study was to develop a
      transdermal gel (2% Klucel(r)) for ondansetron, a first line 5-HT3-receptor
      antagonist antiemetic. The effects of the penetration enhancer camphor and
      isopropyl-myristate (IPM) were first investigated in-vitro using modified Franz
      diffusion-cells and then tested in-vivo in a rabbit model by measuring skin and
      plasma concentrations. Since a disadvantage of transdermal delivery is a
      prolonged lag-time, the effect of skin treatment with a micro-needle roller was
      tested. The in-vitro permeation studies through excised porcine ear skin showed
      that the presence of 2.5% camphor or IPM increased steady state flux by 1.2- and
      2.5-fold, respectively, compared to the control gel. Ondansetron was not
      detectable in either skin or plasma following in-vivo application of the base
      gel, whereas the camphor gel and IPM gel delivered 20 and 81 ug/cm(2) of
      ondansetron, respectively. Microporation led to an increase in plasma Cmax and
      AUC by 10.47 +/- 1.68-fold and 9.31 +/- 4.91-fold, respectively, for the camphor
      gel, and by 2.31 +/- 0.53-fold and 1.59 +/- 0.38-fold, respectively for the IPM
      gel. In conclusion, the 2.5% IPM gel demonstrated optimal in-vivo transdermal
      flux. Skin pretreatment with a micro-needle roller slightly improved the delivery
      of the IPM gel, whereas dramatically increased the transdermal delivery of the
      camphor gel. 

PMID- 24919507
TI  - Vitamin D analogs combined with 5-fluorouracil in human HT-29 colon cancer
      treatment.
AB  - In the present study, we evaluated the antitumor effect of two synthetic analogs
      of vitamin D, namely PRI-2191 [(24R)-1,24-dihydroxyvitamin D3] and PRI-2205 (5,6
      trans calcipotriol), in combined human colon HT-29 cancer treatment with 5
      fluorouracil (5-FU). Mice bearing HT-29 tumors transplanted subcutaneously or
      orthotopically were injected with vitamin D analogs and 5-FU in various
      schedules. A statistically significant inhibition of subcutaneous or orthotopic
      tumor growth was observed as a result of combined therapy. In HT-29 tumors and in
      cells from in vitro culture, we observed increased vitamin D receptor (VDR)
      expression after treatment with either PRI-2205 or 5-FU alone, or in combination.
      Moreover, PRI-2205 decreased the percentage of cells from intestinal tumors in
      G2/M and S stages and increased sub-G1. Increased VDR expression was also
      observed after combined treatment of mice with 5-FU and PRI-2191. Moreover, our
      docking studies showed that PRI-2205 has stronger affinity for VDR, DBP and
      CAR/RXR ligand binding domains than PRI-2191. PRI-2191 analog, used with 5-FU,
      increased the percentage of subcutaneous tumor cells in G0/G1 and decreased the
      percentage in G2/M, S and sub-G1 populations as compared to 5-FU alone. In in
      vitro studies, we observed increased expression of p21 and p-ERK1/2 diminution
      via use of both analogs as compared to use of 5-FU alone. Simultaneously, PRI
      2191 antagonizes some pro-apoptotic activities of 5-FU in vitro. However, in
      spite of these disadvantageous effects in terms of apoptosis, the therapeutic
      effect expressed as tumor growth retardation by PRI-2191 is significant. Our
      results suggest that the mechanism of potentiation of 5-FU antitumor action by
      both analogs is realized via increased p21 expression and decreased p-ERK1/2
      level which may lead to diminution of thymidylate synthase expression. Higher
      binding affinity for VDR, DBP, but also for CAR?RXR ligand binding domain of PRI
      2205 may, in part, explain its very low toxicity with sustained anticancer
      activity.

PMID- 24919509
TI  - A genome-wide association study of serum levels of prostate-specific antigen in
      the Japanese population.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is a useful marker for prostate
      cancer (PCa) and is widely used for screening of PCa. Previous studies have shown
      that genetic components influence the levels of PSA, and some of these genetic
      components would lead to better diagnostic sensitivity and specificity to PCa.
      However, genetic studies for PSA from Asian countries are limited. Our aim was to
      identify genetic components influencing PSA levels in the Japanese population
      using genome-wide association study (GWAS) and to analyse whether genetic
      components would lead to better screening abilities of PCa. METHODS: We performed
      a GWAS comprising 1086 male subjects using 303 283 single nucleotide proteins,
      followed by a replication study of 1302 subjects. PSA levels were quantified by
      chemiluminescence immunoassay method. Quantitative linear regression analysis was
      performed to assess genetic components of PSA levels. A total of 413 subjects
      with prostate biopsies were analysed to examine whether genetic determinants
      would improve diagnostic ability. RESULTS: Rs16856139 in SLC45A3, the same region
      as the previous Chinese study, showed an overall significant association with PSA
      levels (p=2.4*10(-11)) along with rs1058205 in KLK3. In silico analysis revealed
      significant association between rs16856139 and expression of SLC45A3. Genetic
      scores of PSA showed a dose-dependent decrease of area under curve (AUC) of PCa
      and successfully subgrouped the individuals with significantly different AUC
      (p<=0.0097). CONCLUSIONS: Rs16856139, associated with the expression of SLC45A3,
      is significantly associated with the levels of PSA in the Japanese population.
      Classification of subjects based on PSA genetic determinants would improve
      screening ability of PSA to detect PCa.

PMID- 24919510
TI  - Breastfeeding Knowledge, Confidence, Beliefs, and Attitudes of Canadian
      Physicians.
AB  - BACKGROUND: Physicians' attitudes and recommendations directly affect
      breastfeeding duration. Yet, studies in many nations have shown that physicians
      lack the skills to offer proper guidance to breastfeeding mothers. OBJECTIVE:
      This study aims to assess breastfeeding knowledge, confidence, beliefs, and
      attitudes of Canadian physicians. METHODS: A breastfeeding questionnaire was
      developed and piloted prior to study enrollment. These questionnaires were sent
      to 1429 pediatricians (PED), 1329 family physicians (FP), and final-year
      pediatric and final-year family medicine residents (PR and FMR). RESULTS: The
      analysis included 397 PED, 322 FP, 17 PR, and 44 FMR who completed the
      questionnaire. Mean overall correct knowledge score was 67.8% for PED, 64.3% for
      FP, 72.7% for PR, and 66.8% for FMR. Two hundred eighty-five PED (74.2%), 228 FP
      (73.1%), 7 PR (41.2%), and 21 FMR (53.8%) felt confident with their breastfeeding
      counseling skills. Less than half (49.6% of PED and 45.4% of FP) believed that
      evaluating breastfeeding was a primary care physician's responsibility, and few
      PED or FP (5.1% and 11.3%) routinely observed breastfeeding in mother-infant
      pairs. CONCLUSION: Several areas of potential deficits were identified in
      Canadian physicians' breastfeeding knowledge. Physicians would benefit from
      greater education and support, to optimize care of infants and their mothers.

PMID- 24919511
TI  - The moral ties that bind . . . Even to out-groups: the interactive effect of
      moral identity and the binding moral foundations.
AB  - Throughout history, principles such as obedience, loyalty, and purity have been
      instrumental in binding people together and helping them thrive as groups,
      tribes, and nations. However, these same principles have also led to in-group
      favoritism, war, and even genocide. Does adhering to the binding moral
      foundations that underlie such principles unavoidably lead to the derogation of
      out-group members? We demonstrated that for people with a strong moral identity,
      the answer is "no," because they are more likely than those with a weak moral
      identity to extend moral concern to people belonging to a perceived out-group.
      Across three studies, strongly endorsing the binding moral foundations indeed
      predicted support for the torture of out-group members (Studies 1a and 1b) and
      withholding of necessary help from out-group members (Study 2), but this
      relationship was attenuated among participants who also had a strong moral
      identity. 

PMID- 24919515
TI  - Darwin as a dermatologist.

PMID- 24919516
TI  - Dermatologic food for thought: a word search challenge.

PMID- 24919518
TI  - Violaceous necrotic plaques on the leg of an immunosuppressed patient.

PMID- 24919519
TI  - JAMA Dermatology Patient Page. Pemphigus.

PMID- 24919520
TI  - Climate change beliefs and perceptions of weather-related changes in the United
      Kingdom.
AB  - Public perception research in different countries has suggested that real and
      perceived periods of high temperature strengthen people's climate change beliefs.
      Such findings raise questions about the climate change beliefs of people in
      regions with moderate climates. Relatively little is known about whether public
      concerns about climate change may also be associated with perceived changes in
      other weather-related events, such as precipitation or flooding. We examine the
      relationship between perceived changes in weather-related events and climate
      change beliefs among U.K. residents at a time of below-average winter
      temperatures and recent flooding. National survey data (n = 1,848) revealed that
      heat waves and hot summers were perceived to have become less common during
      respondents' lifetimes, while flooding, periods of heavy rainfall, coastal
      erosions, and mild winters were perceived to have increased in frequency and cold
      winters were perceived to be unchanged. Although perceived changes in hot-weather
      related events were positively associated with climate change beliefs, perceived
      changes in wet-weather-related events were found to be an even stronger
      predictor. Self-reported experience of "flooding in own area" and "heat-wave
      discomfort" also significantly contributed to climate change beliefs. These
      findings highlight the importance of salient weather-related events and
      experiences in the formation of beliefs about climate change. We link our
      findings to research in judgment and decision making, and propose that those
      wishing to engage with the public on the issue of climate change should not limit
      their focus to heat. 

PMID- 24919521
TI  - The clinical characteristics and new classification of sticky eyelid syndrome in
      East Asian patients.
AB  - PURPOSE: The aim of this study was to demonstrate the characteristics of sticky
      eyelid syndrome (SES) and to suggest a modified definition and new classification
      of the disease in relation to the severity of the syndrome in East Asian
      patients. METHODS: Forty-four eyes of 31 patients with sticky eyelid syndrome
      were included in this study. The medical records of patients who were diagnosed
      with sticky eyelid syndrome were retrospectively reviewed. Sticky eyelid syndrome
      was defined as an abnormal adhesion between the upper and lower eyelids during
      blinking. We divided the subjects into four grades according to the severity of
      the disease. RESULTS: Among 31 patients, there were 10 men and 21 women. The mean
      age of patients was 62.5 years. A total of 13 patients had SES bilaterally. All
      patients had meibomian gland dysfunction (MGD). Thirty-three eyes had
      dermatochalasis, and 30 eyes had involutional ptosis. Horizontal lower lid laxity
      was observed in 23 eyes, and reverse ptosis found in 15 eyes. Patients were
      classified into four groups as follows: G1: 11 (25%), G2: 24 (54.5%), G3: 6
      (13.6%) and G4: 3 eyes (6.8%). Patients in Grade 1 tended to improve only with
      medical treatment for MGD. However, surgical management was necessary for
      patients in Grades 3 and 4. CONCLUSIONS: Meibomian gland dysfunction is a
      fundamental risk factor for developing sticky eyelid syndrome. Further, combined
      upper lid ptosis or lower lid laxity may be aggravating factors. According to the
      grading, medical or surgical management can be chosen.

PMID- 24919522
TI  - The effect of ethanol on cell properties and steroid 1-en-dehydrogenation
      biotransformation of Arthrobacter simplex.
AB  - Resting cells of Arthrobacter simplex with 1-en-dehydrogenation ability were
      prepared and treated by ethanol at subinhibitory concentrations (4%-15%, v/v),
      then added into the ethanol-free system containing low concentration of cortisone
      acetate (1 g L(-1)) to produce prednisone acetate by C1,2 dehydrogenation
      reaction. Results showed that, within the range of ethanol concentration, the
      initial conversion rate was varied significantly with the concentration of
      ethanol and the maximum was obtained at 8% (v/v) ethanol, which was increased by
      32.6% compared with the control. A series of cell features closely relevant to
      biotransformation efficiency were further analyzed. It indicated that ethanol
      acting on cell wall and membrane could be used as a mediator to enhance cell
      permeability, which facilitated the penetration of substrate across cell barrier
      within a short time, resulting in the elevated initial conversation rate. The
      observation of fatty acids composition suggested that the increased unsaturated
      fatty acids, especially cis-isomers, in the presence of ethanol led to the
      disorganization of the native arrangement of lipids and thus increased cell
      permeability. Our findings demonstrated that another facilitation of ethanol was
      to promote substrate transport into cells by permeabilization, which would
      provide the guidance in the practical application of organic solvents in steroid
      biotransformation.

PMID- 24919523
TI  - Potentially inappropriate prescribing among older people in the United Kingdom.
AB  - BACKGROUND: Potentially inappropriate prescribing (PIP) in older people is
      associated with increases in morbidity, hospitalisation and mortality. The
      objective of this study was to estimate the prevalence of and factors associated
      with PIP, among those aged >=70 years, in the United Kingdom, using a
      comprehensive set of prescribing indicators and comparing these to estimates
      obtained from a truncated set of the same indicators. METHODS: A retrospective
      cross-sectional study was carried out in the UK Clinical Practice Research
      Datalink (CPRD), in 2007. Participants included those aged >= 70 years, in CPRD.
      Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially
      Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed
      drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according
      to individual STOPP criteria were estimated. The relationship between PIP and
      polypharmacy (>=4 medications), comorbidity, age, and gender was examined. A
      truncated, subset of 28 STOPP criteria that were used in two previous studies,
      were further applied to the data to facilitate comparison. RESULTS: Using 52
      indicators, the overall prevalence of PIP in the study population (n = 1,019,491)
      was 29%. The most common examples of PIP were therapeutic duplication (11.9%),
      followed by use of aspirin with no indication (11.3%) and inappropriate use of
      proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with
      polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05).
      PIP was more common in those aged 70-74 years vs. 85 years or more and in males.
      Application of the smaller subset of the STOPP criteria resulted in a lower PIP
      prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP
      issues identified with this subset were use of PPIs at maximum dose for > 8
      weeks, NSAIDs for > 3 months, and use of long-term neuroleptics. CONCLUSIONS: PIP
      was prevalent in the UK and increased with polypharmacy. Application of the
      comprehensive set of STOPP criteria allowed more accurate estimation of PIP
      compared to the subset of criteria used in previous studies. These findings may
      provide a focus for targeted interventions to reduce PIP.

PMID- 24919524
TI  - Endogenous interleukin-6 amplifies interleukin-17 production and corticoid
      resistance in peripheral T cells from patients with multiple sclerosis.
AB  - Interleukin-6 (IL-6) has been implicated in the induction of pathogenic IL-17
      producing T cells in autoimmune diseases, and studies evaluating the role of this
      cytokine in T-cell function in patients with multiple sclerosis (MS) are lacking.
      Our objective was to evaluate the role of IL-6 receptor (IL-6R) signalling on in
      vitro functional status of T cells from patients with relapsing-remitting MS
      during clinical remission. Our results demonstrated that, even during the
      remission phase, activated T cells from patients produce higher levels of IL-17,
      and this cytokine was positively correlated with disease severity, as determined
      by Expanded Disability Status Scale score. In the MS group, the blockade of IL-6R
      signalling by anti-IL-6R monoclonal antibody reduced IL-17 production and
      elevated IL-10 release by activated CD4(+) T cells, but it did not alter the
      production of these cytokines by activated CD8(+) T cells. Blockade of IL-6R
      signalling also reduced the ability of monocytes to up-regulate T helper type 17
      phenotype in patients with MS. Finally, both cell proliferation and IL-17 release
      by CD4(+) and, mainly, CD8(+) T cells from patients with MS were less sensitive
      to hydrocortisone inhibition than control group. Interestingly, IL-6R signalling
      blockade restored the ability of hydrocortisone to inhibit both T-cell
      proliferation and IL-17 production. Collectively, these results suggest that IL-6
      might be involved in MS pathogenesis by enhancing IL-17 production and reducing
      corticoid inhibitory effects on activated T cells. 

PMID- 24919525
TI  - The combinational use of CRISPR/Cas9-based gene editing and targeted toxin
      technology enables efficient biallelic knockout of the alpha-1,3
      galactosyltransferase gene in porcine embryonic fibroblasts.
AB  - BACKGROUND: The recent development of the type II clustered regularly interspaced
      short palindromic repeats (CRISPR)/Cas9 system has enabled genome editing of
      mammalian genomes including those of mice and human; however, its applicability
      and efficiency in the pig have not been studied in depth. Here, using the
      CRISPR/Cas9 system, we aimed to destroy the function of the porcine alpha-1,3
      galactosyltransferase (alpha-GalT) gene (GGTA1) whose product is responsible for
      the synthesis of the alpha-Gal epitope, a causative agent for hyperacute
      rejection upon pig-to-human xenotransplantation. METHODS: Porcine embryonic
      fibroblasts were transfected with a Cas9 expression vector and guide RNA
      specifically designed to target GGTA1. At 4 days after transfection, the cells
      were incubated with IB4 conjugated with saporin (IB4SAP), which eliminates alpha
      Gal epitope-expressing cells. Therefore, the cells surviving after IB4SAP
      treatment would be those negative for alpha-Gal epitope expression, which in turn
      indicates the generation of GGTA1 biallelic knockout (KO) cells. RESULTS: Of the
      1.0 * 10(6) cells transfected, 10-33 colonies survived after IB4SAP treatment,
      and almost all colonies (approximately 90%) were negative for staining with red
      fluorescence-labeled IB4. Sequencing of the mutated portion of GGTA1 revealed a
      frameshift of the alpha-GalT protein. Porcine blastocysts derived from the
      somatic cell nuclear transfer of these alpha-Gal epitope-negative cells also
      lacked the alpha-Gal epitope on their surface. CONCLUSIONS: These results
      demonstrated that the CRISPR/Cas9 system can efficiently induce the biallelic
      conversion of GGTA1 in the resulting somatic cells and is thus a promising tool
      for the creation of KO cloned piglets.

PMID- 24919526
TI  - Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide
      as add-on therapies in patients whose type 2 diabetes mellitus is inadequately
      controlled with metformin.
AB  - AIMS: To assess the long-term glycaemic durability, safety and tolerability of
      dapagliflozin versus glipizide as add-on therapies in patients with type 2
      diabetes inadequately controlled by metformin alone. METHODS: This was a 52-week,
      randomised, double-blind study of dapagliflozin (n = 406) versus glipizide (n =
      408), uptitrated over 18 weeks according to tolerability and glycaemic response
      to a maximum of 10 and 20 mg/day, respectively, as add-on therapies to metformin
      (>= 1500 mg/day) with a 156-week double-blind extension period. Data over 104
      weeks are reported here. RESULTS: In total, 53.1% of patients completed 104 weeks
      of treatment. After the greater initial decrease (0-18 weeks) in glycated
      haemoglobin (HbA1c) with glipizide, the 18-104-week HbA1c coefficient of failure
      (CoF) was lower with dapagliflozin (0.13%/year) than with glipizide (0.59%/year),
      resulting in significant dapagliflozin versus glipizide differences of 
      0.46%/year (95% CI -0.60,-0.33; p = 0.0001) for CoF and -0.18%(-2.0 mmol/mol)
      [95% CI -0.33(-3.6),-0.03(-0.3); p = 0.021] for 104-week HbA1c. Dapagliflozin
      produced sustained reductions in weight and systolic blood pressure, whereas
      glipizide increased weight and systolic blood pressure, giving 104-week
      dapagliflozin versus glipizide differences of -5.1 kg (95% CI: -5.7,-4.4) and 
      3.9 mmHg (95% CI: -6.1,-1.7), respectively. Over 104 weeks, the hypoglycaemia
      rate was 10-fold lower with dapagliflozin than with glipizide (4.2 vs. 45.8%),
      whereas patient proportions with events suggestive of genital infection and of
      urinary tract infection (UTI) were greater with dapagliflozin (14.8 and 13.5%,
      respectively) than with glipizide (2.9 and 9.1%, respectively). CONCLUSIONS: Over
      2 years, compared with glipizide, dapagliflozin demonstrated greater glycaemic
      durability, sustained reductions in weight and systolic blood pressure and a low
      hypoglycaemia rate; however, genital infections and UTIs occurred more
      frequently.

PMID- 24919527
TI  - [Consensus statement on the evaluation and therapy of chronic cough in children].
AB  - BACKGROUND: Currently no consensus guidelines on the evaluation and therapy of
      chronic cough in children have been published in German. Aim of this study was
      therefore, after a literature search on all relevant publications and guidelines
      concerning chronic cough in children, to publish a Statement of the Austrian
      Society of Pediatrics and The Austrian Society of Pneumology on the evaluation
      and therapy of chronic childhood cough and to publish a practice based approach.
      Aim was also to differentiate cough clearly from obstructive airway diseases and
      to summarize all relevant differential diagnosis using relevant patient history
      and clinical characteristics and give an overview of therapeutical approaches.
      The subjective component of cough and the difficulty to assess cough in an
      objective manner is discussed. METHODS: A Cochrane and Medline Search were
      performed on all relevant literature until Mai 2013. RESULTS: Chronic cough in
      children is defined as daily cough for more than 4 weeks. Duration of 3 to 8
      weeks is sometimes called prolonged or sub-acute cough. Chronic cough may have
      specific cause and may be a symptom of an underling disease, which needs to be
      found and treated adequately. Unspecific cough may only be diagnosed after
      exclusion of all other causes. Any therapeutical approach needs to be re-
      evaluated and efficacy needs to be reviewed. Parental understanding of the
      etiology of cough in general and the influence of environmental exposures is
      essential for diagnosis. CONCLUSION: Chronic cough needs a detailed history and
      various differential diagnoses need to be taken in consideration. Children with
      persistent complaints without a proper diagnosis need to be seen in a center
      specialized in Pediatric Respiratory Medicine.

PMID- 24919528
TI  - Opportunistic screening for atrial fibrillation during follow-up of patients with
      treated hypertension.

PMID- 24919529
TI  - Regarding: "Strontium ranelate stimulates the activity of bone-specific alkaline
      phosphatase: interaction with Zn2+ and Mg 2+".

PMID- 24919531
TI  - Formation of osteoclasts on calcium phosphate bone cements and polystyrene
      depends on monocyte isolation conditions.
AB  - OBJECTIVES: Peripheral blood mononuclear cells (PBMC) are an attractive source
      for the generation of osteoclasts in vitro, which is an important prerequisite
      for the examination of resorption and remodeling of biomaterials. In this study,
      different preparation methods are used to obtain cell populations with a rising
      content of CD14(+) monocytes. We wanted to address the question whether there is
      a correlation between content of CD14(+) cells in the preparation and
      functionality of formed osteoclasts. MATERIALS AND METHODS: PBMC obtained by
      density gradient centrifugation with and without further purification by plastic
      adherence or immunomagnetic separation of CD14(+) cells were seeded on both cell
      culture polystyrene and a calcium phosphate bone cement (CPC) and cultivated
      under stimulation with macrophage colony-stimulating factor (M-CSF) and receptor
      activator of nuclear factor-kappa B ligand (RANKL). Cell cultures were
      characterized by histological and fluorescent staining of multinucleated cells
      that were positive for tartrate-resistant acid phosphatase (TRAP) activity and
      the presence of actin rings, respectively. Furthermore, activities of osteoclast
      marker enzymes TRAP and carbonic anhydrase II (CA II) were quantified. For
      osteoclasts cultured on CPC, resorption pits were visualized using scanning
      electron microscopy (SEM). RESULTS: Monocytes of all preparations were
      successfully differentiated into multinucleated osteoclasts showing TRAP and CA
      II activity on both cell culture plastic and CPC. Preparations involving an
      additional plastic adherence step exhibited only a minor increase of TRAP and CA
      II activity in the second week of cultivation. Furthermore, the number of
      resorption pits on CPC was reduced in these cultures compared with
      immunomagnetically enriched monocytes and preparations without additional plastic
      adherence steps. Optimal results with regard to yield, number of multinucleated
      osteoclasts, activity of TRAP and CA II, and resorption of CPC were obtained by
      simple density gradient centrifugation. CONCLUSION: All examined monocyte
      preparation protocols were suitable for the generation of osteoclasts on both
      polystyrene and CPC. Highly purified monocytes are not mandatory to obtain
      functional osteoclasts for investigation of biomaterial resorption.

PMID- 24919530
TI  - Oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA), a
      hidden resistant mechanism among clinically significant isolates in the Wessex
      region/UK.
AB  - PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) is defined as S.
      aureus genetically having the mecA or mecC genes or phenotypically showing
      minimum inhibitory concentration (MIC) of oxacillin higher than 2 mg/L. However,
      recently, cefoxitin/oxacillin-susceptible mecA-positive S. aureus (OS-MRSA) has
      been reported worldwide. Little is known about the prevalence and virulence of
      these strains among clinically significant isolates in the UK. The aims were to
      (1) investigate the prevalence of OS-MRSA in seven major hospitals in the Wessex
      region/UK from a cohort of 500 clinically significant phenotypically identified
      MSSA isolates, (2) genetically characterise OS-MRSA strains by pulsed-field gel
      electrophoresis (PFGE) and compare these to common UK epidemic strains; and (3)
      to determine Panton-Valentine leukocidin (PVL; lukFS) gene carriage rates among
      these isolates. RESULTS: OS-MRSA was found in six isolates (1.2 %) of
      phenotypically identified and reported MSSA isolates by conventional methods.
      PFGE showed OS-MRSA strains to be genetically diverse and distinct from the
      common UK epidemic strains EMRSA-15 and EMRSA-16. None of these OS-MRSA stains
      carried the genes encoding PVL; however, overall positivity rate for PVL was 4.4
      %, much higher than the nationally reported rates of 2 % in the UK. CONCLUSION:
      There are still many unknowns regarding phenotypic and/or genetic
      characterization of the emerging OS-MRSA isolates in the UK and worldwide. Data
      regarding their epidemiology and optimal therapy for infection are limited and
      need further investigation not only in the UK, but also worldwide, as it is
      likely to have an impact on the empirical treatment of S. aureus infections.

PMID- 24919532
TI  - Effect of different cleaning regimens on the adhesion of resin to saliva
      contaminated ceramics.
AB  - PURPOSE: The aim of this study was to evaluate the influence of different
      cleaning regimens on the microshear bond strength (MUSBS) of three different all
      ceramic surfaces after saliva contamination. MATERIAL AND METHODS: Cubic ceramic
      specimens (3 * 3 * 3 mm(3) ) were prepared from three types of ceramics:
      zirconium dioxide (Z), leucite-reinforced glass ceramic (E), lithium disilicate
      glass ceramic (EX; n = 12/subgroup). A total of 144 composite resin cylinders
      (diameter: 1 mm, height: 3 mm) were prepared. Three human-saliva-contaminated
      surfaces of ceramic specimens were cleaned with either water spray (WS), with
      0.5% sodium hypochlorite solution (HC), or with a cleaning paste (CP). Control
      surface (C) was not contaminated or cleaned. Composite cylinders were bonded to
      each surface with a resin luting cement. All specimens were stored at 37 degrees
      C in deionized water until fracture testing. MUSBS tests were performed in a
      universal testing machine (0.5 mm/min), and the results (MPa +/- SD) were
      statistically analyzed (two-way ANOVA, Bonferroni a = 0.05). Fractured surfaces
      were analyzed to identify the failure types using an optical microscope at 50*
      magnification. Two representative specimens from all groups were examined with
      scanning electron microscopy. RESULTS: MUSBS test results were significantly
      affected by the saliva cleaning regimens (p = 0.01) and the ceramic types (p =
      0.03). The interaction terms between the ceramic type and saliva cleaning regimen
      were also significant (p < 0.05). There were no significant differences among the
      MUSBS values (MPa +/- SD) for the Z group (C = 17.5 +/- 8.8; WS = 16.0 +/- 4.9;
      HC = 17.6 +/- 5.8; CP = 16.6 +/- 7.5; p > 0.05). In the EX group, C resulted in
      significantly higher MUSBS values (32.6 +/- 7.4) than CP (17.4 +/- 8.9), WS (15.6
      +/- 7.3), and HC (14.3 +/- 4.5) (p < 0.05); however, C (20.4 +/- 7.1) and HC
      (19.2 +/- 7.5) showed higher MUSBS values than CP (13.8 +/- 4.8) and WS (10.9 +/-
      5.7) in the E group. Some cohesive failures within the luting resin were observed
      in the E and EX groups, whereas only adhesive failures were seen in zirconia
      groups for all surface treatments. CONCLUSIONS: Different ceramic surface
      cleaning regimens after saliva contamination of the zirconium dioxide revealed
      MUSBS similar to the control group, whereas all surface cleaning regimens tested
      significantly decreased the bond strength values in the lithium disilicate glass
      ceramic. The leucite-reinforced glass-ceramic group benefited from 0.5% sodium
      hypochlorite solution cleaning with increased bond strengths. CLINICAL
      SIGNIFICANCE: Adhesive cementation of zirconia presents a clinically challenging
      protocol, and the cementation surface contamination of the zirconia restorations
      and the inadequate removal of the contaminants increase the risk of failure, as
      for all ceramic types. This study demonstrated that surface cleaning regimens
      should be applied according to different ceramic properties.

PMID- 24919533
TI  - More than 20-year experience of Bentall operation with mechanical prostheses for
      chronic aortic root aneurysm.
AB  - OBJECTIVES: Long-term results of Bentall operations with mechanical prostheses
      were analyzed and evaluated over 30 years. METHODS: Seventy-one patients aged
      50.2 +/- 1.8 years old underwent an elective Bentall operation from 1975 to 2013
      for chronic aortic root aneurysm, while 129 patients aged 51.6 +/- 1.3 underwent
      isolated AVR with a mechanical valve for pure aortic regurgitation. The follow-up
      was completed for a total of 2,336-patient-years in 99.5% of these patients.
      RESULTS: No significant differences were observed in the hospital mortality (2.8
      and 0.78%), actuarial survival rate (43.3 +/- 9.9 and 50.0 +/- 9.2%), freedom
      from valve-related death (84.9 +/- 6.8 and 68.1 +/- 11%), and freedom from valve
      related morbidity (43.7 +/- 19 and 40.1 +/- 15%) at 30 years between the two
      groups. No significant differences were observed in the valve-related events;
      however, a higher incidence of rupture of aortic aneurysm was observed in the
      Bentall group (P = 0.0005). CONCLUSIONS: Both our short- and long-term results of
      Bentall operation with mechanical prostheses were satisfactory at 30 years after
      the surgery and were comparable with those of simple AVR. However, to prevent
      rupture of the aortic aneurysm, special care should be taken after the primary
      Bentall operations.

PMID- 24919534
TI  - Repeated stress exposure causes strain-dependent shifts in the behavioral
      economics of cocaine in rats.
AB  - Cocaine-experienced Wistar and Wistar Kyoto (WKY) rats received four daily
      repeated forced swim stress sessions (R-FSS), each of which preceded 4-hour
      cocaine self-administration sessions. Twenty-four hours after the last swim
      stress, cocaine valuation was assessed during a single-session threshold
      procedure. Prior exposure to R-FSS significantly altered cocaine responding in
      Wistar, but not WKY, rats. Behavioral economic analysis of responding revealed
      that the Wistar rats that had received R-FSS exhibited an increase in the maximum
      price that they were willing to pay for cocaine (Pmax ). Pre-treatment with the
      long-lasting kappa opioid receptor (KOR) antagonist norbinaltorphimine prevented
      the stress-induced increase in Pmax . Thus, R-FSS exposure had strain-dependent
      effects on cocaine responding during the threshold procedure, and the stress
      effects on cocaine valuation exhibited by Wistar, but not WKY, required intact
      KOR signaling. 

PMID- 24919535
TI  - Bacteriocin production and gene sequencing analysis from vaginal Lactobacillus
      strains.
AB  - The human vagina is a complex and dynamic ecosystem containing an abundance of
      microorganisms. In women of childbearing age, this system is dominated by
      Lactobacillus spp. In the present work, seventeen newly isolated vaginal strains
      were identified by 16S rDNA sequencing and were investigated for their
      antimicrobial properties. Twelve of the isolated Lactobacillus strains showed
      activity against one or more microorganisms. Six and five of them produced
      substances that inhibited the growth of two different Klebsiella strains and
      Staphylococcus aureus, respectively. Two lactobacilli strains were active against
      an Escherichia coli strain, one isolate was active against an Enterococus
      faecalis strain and another lactobacilli strain showed antimicrobial activity
      against a Candida parapsilosis strain. The nature of the active compounds was
      additionally studied, and the presence of bacteriocin-like substances was proved.
      The genes related to the bacteriocin production in three of the newly isolated
      strains were identified and sequenced. The presence of gassericin A operon in the
      genome of the species Lactobacillus crispatus was described for the first time.
      The presence of antimicrobial activity contributes to their possible use as
      potential probiotic strains after further research. 

PMID- 24919536
TI  - A comparative study of the effect of probiotics on cariogenic biofilm model for
      preventing dental caries.
AB  - Dental caries is induced by oral biofilm containing Streptococcus mutans.
      Probiotic bacteria were mainly studied for effect on the gastrointestinal tract
      and have been known to promote human health. However, the information of
      probiotics for oral health has been lack yet. In this study, we investigated
      influence of various probiotics on oral bacteria or cariogenic biofilm and
      evaluated candidate probiotics for dental caries among them. The antimicrobial
      activity of the spent culture medium of probiotics for oral streptococci was
      performed. Probiotics were added during the biofilm formation with salivary
      bacteria including S. mutans. The oral biofilms were stained with a fluorescent
      dye and observed using the confocal laser scanning microscope. To count bacteria
      in the biofilm, the bacteria were plated on MSB and BHI agar plates after
      disrupting the biofilm and cultivated. Glucosyltransferases (gtfs) expression of
      S. mutans and integration of lactobacilli into the biofilm were evaluated by real
      time RT-PCR. Among probiotics, Lactobacillus species strongly inhibited growth of
      oral streptococci. Moreover, Lactobacillus species strongly inhibited formation
      of cariogenic biofilm model. The expression of gtfs was significantly reduced by
      Lactobacillus rhamnosus. The integration of L. rhamnosus into the biofilm model
      did not exhibit. However, L. acidophilus and L casei integrated into the biofilm
      model. These results suggest that L. rhamnosus may inhibit oral biofilm formation
      by decreasing glucan production of S. mutans and antibacterial activity and did
      not integrate into oral biofilm, which can be a candidate for caries prevention
      strategy. 

PMID- 24919537
TI  - What ever happened to the "cool" kids? Long-term sequelae of early adolescent
      pseudomature behavior.
AB  - Pseudomature behavior-ranging from minor delinquency to precocious romantic
      involvement-is widely viewed as a nearly normative feature of adolescence. When
      such behavior occurs early in adolescence, however, it was hypothesized to
      reflect a misguided overemphasis upon impressing peers and was considered likely
      to predict long-term adjustment problems. In a multimethod, multireporter study
      following a community sample of 184 adolescents from ages 13 to 23, early
      adolescent pseudomature behavior was linked cross-sectionally to a heightened
      desire for peer popularity and to short-term success with peers. Longitudinal
      results, however, supported the study's central hypothesis: Early adolescent
      pseudomature behavior predicted long-term difficulties in close relationships, as
      well as significant problems with alcohol and substance use, and elevated levels
      of criminal behavior. 

PMID- 24919538
TI  - Gender-related differences in outcomes and resource utilization in patients
      undergoing radiofrequency ablation of supraventricular tachycardia: results from
      Patients' Perspective on Radiofrequency Catheter Ablation of AVRT and AVNRT
      Study.
AB  - AIMS: The aim of this study was to describe gender-related differences in
      clinical presentation, radiofrequency ablation (RFA) outcomes, and healthcare
      resource utilization in a group of patients with atrioventricular nodal
      reciprocating tachycardia (AVNRT) and atrioventricular reciprocating tachycardia
      (AVRT). METHODS AND RESULTS: This was a single-centre, prospective, cohort study
      which enroled 82 patients undergoing RFA of AVNRT or AVRT. At baseline, all
      patients received a clinical assessment and completed questionnaires concerning:
      socioeconomic status, disease-specific symptoms (Patient Perception of Arrhythmia
      Questionnaire; PPAQ), health-related quality of life (HRQoL) (EQ-5D-3L), and
      healthcare resource utilization. Two months after RFA, the clinical assessment
      was repeated and subjects completed PPAQ and EQ-5D-3L. Follow-up was completed by
      64 patients, 41 (64%) women. At baseline, there were no significant differences
      in baseline characteristics, except AVNRT prevalence, and HRQoL by gender but
      women reported higher severity of symptoms on PPAQ than men (2.8 vs. 2.4 points,
      P < 0.001). At 2 months after RFA, women still reported higher severity of
      symptoms (1.8 vs. 0 points; P = 0.02) on PPAQ and more heart skipping than men
      (54 vs. 13%; P = 0.0014); differences in EQ-5D-3L index and EQ-VAS were
      insignificant. There was no significant difference in healthcare resource
      utilization during the year preceding RFA, but antiarrhythmic drugs were
      significantly more often prescribed to women pre-procedure (30 vs. 8%; P =
      0.022). CONCLUSION: There is a small but significant gender-related difference in
      outcome of RFA in patients with AVNRT or AVRT measured with a disease-specific
      instrument. No significant difference in HRQoL or access to healthcare resources
      between women and men was found.

PMID- 24919539
TI  - A simple infection-control protocol to reduce serious cardiac device infections.
AB  - AIM: Device infection is a serious complication and is considered procedure
      related if occurring within 12 months of an intervention. We analysed the
      effectiveness of a simple infection-control protocol (ICP) at reducing cardiac
      device infections (CDIs) in a tertiary referral centre. METHODS AND RESULTS:
      Prior to the introduction of a new ICP, we retrospectively analysed all simple
      and complex device implants, related procedures, and infections over a 3-year
      period. A new protocol was implemented from November 2007, including antibiotic
      prophylaxis determined by risk stratification, improved glycaemic control,
      specific skin preparation, and closure techniques, as well as different diathermy
      settings. Follow-up data for all patients were collected. Risk factors for
      infection were compared between pre- and post-intervention groups to ensure that
      the populations were comparable. A cost analysis of CDI and a review of the
      commonly identified micro-organisms were also undertaken. One thousand seven
      hundred and ninety-eight procedures were performed between November 2004 and
      November 2007 and 981 procedures between November 2007 and May 2009. There were
      no significant differences in the risk factors for infection between the two
      groups. Following the introduction of the ICP, there was a 54% reduction in the
      incidence of CDI from 1.3 to 0.6% (P < 0.03; CI 0.25, 1.36). Most patients with
      CDI had negative blood cultures or grew Staphylococcus sp. The average cost was
      L30 958.40 per infection incident and the cost of the new ICP was minimal.
      CONCLUSIONS: A significant reduction in CDI can be achieved with the introduction
      of a simple ICP with substantial cost savings.

PMID- 24919540
TI  - Effects of a multimodality blood conservation schema toward improvement of
      intraoperative hemoglobin levels and off-pump transfusions in coronary artery
      bypass graft surgery.
AB  - BACKGROUND: Cardiothoracic surgery places significant demands on blood bank
      resources. Measures aimed at reducing intraoperative hemodilution were initiated
      as part of a blood conservation program. STUDY DESIGN AND METHODS: We initiated a
      series of measures aimed at reducing hemodilution volume: 1) reduction of
      intravenous fluid (IVF) volume, 2) reduction of circuit size, and 3) use of
      autologous priming techniques. All sources and volumes of IVF were obtained from
      the medical record. Intraoperative hematocrit (Hct) measurements were performed
      at the following intervals: first in operating room (OR), lowest on-pump, last on
      pump, after protamine reversal, and immediately before discharge from OR. Red
      blood cell (RBC) transfusions were recorded. Intraoperative IVF, Hct levels, and
      transfusions were analyzed by cardiopulmonary bypass phase (prepump, on-pump, and
      off-pump), comparing preimplementation and postimplementation periods. RESULTS:
      Total intraoperative IVF volume was reduced by 973.7 mL (95% confidence interval,
      671.6-1275.9 mL; p < 0.001) leading to a mean on-pump Hct improvement of more
      than 2% (p < 0.004). This contributed to a reduction in off-pump RBC transfusions
      by 20.6% (p = 0.014). A significant degree of heterogeneity in transfusion
      practice was noted between anesthesiologists. CONCLUSIONS: Blood conservation
      efforts in cardiac surgery should include efforts aimed at reducing hemodilution.
      Potential improvements are blunted by variation in transfusion practice.

PMID- 24919541
TI  - Localization of the androgen-synthesizing enzymes, androgen receptor, and sex
      steroids in the vagina: possible implications for the treatment of postmenopausal
      sexual dysfunction.
AB  - INTRODUCTION: To better understand the mechanisms underlying the beneficial
      effects of the intravaginal administration of dehydroepiandrosterone (DHEA)
      observed in postmenopausal women on sexual dysfunction. AIMS: To identify the
      distribution of the androgen-synthesizing enzymes as well as androgen receptor
      (AR) and measure steroid levels in the monkey vagina. METHODS: The cynomolgus
      monkey (Macaca fascicularis), the closest model to the human, has been used to
      measure the expression levels of steroidogenic enzymes and androgen receptor by
      quantitative reverse transcription polymerase chain reaction (n=4), confirmed by
      immunohistochemistry, and immunofluorescence (n=3). DHEA and its androgenic
      metabolites were quantified by LC-MS/MS (n=4). MAIN OUTCOME MEASURES: The
      presence of SRD5A1, SRD5A2, HSD17B3, AR as well as nerve fibers (PGP 9.5) was
      investigated, and steroid levels were measured. RESULTS: AR is widely distributed
      within the vaginal epithelium and also in the lamina propria with a lower
      expression in the muscularis layer and blood vessel walls. Androgen-forming
      enzymes, on the other hand, are expressed in the vaginal stratified squamous
      epithelium at a relatively high level where they are uniformly distributed from
      the basal membrane up to the superficial keratinized cells. The enzymes are at a
      lower level in blood vessel walls and zona muscularis where nerve fibers are
      localized. DHEA and its androgen metabolites are present at biologically
      significant concentrations in the monkey vagina. CONCLUSION: The enzymes
      responsible for androgen formation as well as AR are at the highest level in the
      superficial layer of the stratified epithelium and muscularis layers of the
      vagina. These data provide a potential explanation for the described role of
      androgens in regulating vaginal lubrication, smooth muscle activity, blood flow,
      and the neuronal activity potentially involved in the correction of sexual
      dysfunction.

PMID- 24919542
TI  - A novel architecture based upon multi-walled carbon nanotubes and ionic liquid to
      improve the electroanalytical detection of ciprofibrate.
AB  - Voltammetric studies have been carried out using a glassy carbon electrode (GCE)
      modified with multi-walled carbon nanotubes (MWCNTs) and the ionic liquid 1-butyl
      3-methylimidazolium chloride (IL). Studies on the electrochemical properties of
      GCEs modified with MWCNTs and IL within different polymeric films
      (dihexadecylphosphate (DHP), Nafion, and chitosan (CTS)) were performed using a
      [Fe(CN)6](4-/3-) electrochemical probe. The modified GCE with different polymeric
      films was also tested for ciprofibrate (CPF) sensing in the presence and absence
      of IL in the film. The presence of IL and the MWCNTs improved the electrochemical
      response for CPF in all cases due to a synergic effect, and the IL-MWCNTs-DHP/GCE
      showed a great voltammetric profile for CPF detection. The IL-MWCNTs-DHP/GCE and
      differential pulse voltammetry (DPV) were used for the determination of CPF. An
      analytical curve was obtained for CPF in the concentration range of 2.50 * 10(-7)
      to 7.41 * 10(-6) mol L(-1) with a detection limit of 9.20 * 10(-8) mol L(-1). The
      proposed DPV method was successfully applied for CPF determination in
      pharmaceutical samples, and the results obtained agree with the results obtained
      using a spectrophotometric method at a confidence level of 95%. 

PMID- 24919543
TI  - Effects of noise on fishes: what we can learn from humans and birds.
AB  - In this paper we describe the masking of pure tones in humans and birds by
      manmade noises and show that similar ideas can be applied when considering the
      potential effects of noise on fishes, as well as other aquatic vertebrates.
      Results from many studies on humans and birds, both in the field and in the
      laboratory, show that published critical ratios can be used to predict the masked
      thresholds for pure tones when maskers consist of complex manmade and natural
      noises. We argue from these data that a single, simple measure, the species
      critical ratio, can be used to estimate the effect of manmade environmental
      noises on the perception of communication and other biologically relevant sounds.
      We also reason that if this principle holds for species as diverse as humans and
      birds, it probably also applies for all other vertebrates, including fishes. 

PMID- 24919544
TI  - Butein suppresses breast cancer growth by reducing a production of intracellular
      reactive oxygen species.
AB  - BACKGROUND: Butein has various functions in human diseases including cancer.
      While anti-cancer effects of butein have been revealed, it is urgent to
      understand a unique role of butein against cancer. In this study, we demonstrate
      that butein inhibition of reactive oxygen species (ROS) production results in
      suppression of breast cancer growth. METHODS: Different breast cancer cell lines
      were treated with butein and then subjected to cell viability and apoptosis
      assays. Butein-sensitive or -resistant breast cancer cells were injected into
      mammary fat pads of immunocompromised mice and then butein was injected. Breast
      cancer cells were categorized on the basis of butein sensitivity. RESULTS: Butein
      reduced viabilities of different breast cancer cells, while not affecting those
      of HER2-positive (HER2+) HCC-1419, SKBR-3 and HCC-2218 breast cancer cells.
      Butein reduction of ROS levels was correlated with apoptotic cell death.
      Furthermore, butein reduction of ROS level led to inhibitions of AKT
      phosphorylation. N-acetyl-L-cysteine (NAC), a free radical scavenger, also
      reduced ROS production and AKT phosphorylation, resulting in apoptotic cell
      death. In contrast, inhibitory effects of both butein and NAC on ROS production
      and AKT phosphorylation were not detected in butein-resistant HER2+ HCC-1419,
      SKBR-3 and HCC-2218 cells. In the in vivo tumor growth assays, butein inhibited
      tumor growth of butein-sensitive HER2+ BT-474 cells, while not affecting that of
      butein-resistant HER2+ HCC-1419 cells. Moreover, butein inhibition of ROS
      production and AKT phosphorylation was confirmed by in vivo tumor growth assays.
      CONCLUSIONS: Our study first reveals that butein causes breast cancer cell death
      by the reduction of ROS production. Therefore, our finding provides better
      knowledge for butein effect on breast cancer and also suggests its treatment
      option.

PMID- 24919545
TI  - Survival of norovirus surrogate on various food-contact surfaces.
AB  - Norovirus (NoV) is an environmental threat to humans, which spreads easily from
      one infected person to another, causing foodborne and waterborne diseases.
      Therefore, precautions against NoV infection are important in the preparation of
      food. The aim of this study was to investigate the survival of murine norovirus
      (MNV), as a NoV surrogate, on six different food-contact surfaces: ceramic, wood,
      rubber, glass, stainless steel, and plastic. We inoculated 10(5) PFU of MNV onto
      the six different surface coupons that were then kept at room temperature for 28
      days. On the food-contact surfaces, the greatest reduction in MNV was 2.28 log10
      PFU/coupon, observed on stainless steel, while the lowest MNV reduction was 1.29
      log10 PFU/coupon, observed on wood. The rank order of MNV reduction, from highest
      to lowest, was stainless steel, plastic, rubber, glass, ceramic, and wood. The
      values of d R (time required to reduce the virus by 90%) on survival plots of MNV
      determined by a modified Weibull model were 277.60 h (R(2) = 0.99) on ceramic,
      492.59 h (R(2) = 0.98) on wood, 173.56 h on rubber (R(2) = 0.98), 97.18 h (R(2) =
      0.94) on glass, 91.76 h (R(2) = 0.97) on stainless steel, and 137.74 h (R(2) =
      0.97) on plastic. The infectivity of MNV on all food-contact surfaces remained
      after 28 days. These results show that MNV persists in an infective state on
      various food-contact surfaces for long periods. This study may provide valuable
      information for the control of NoV on various food-contact surfaces, in order to
      prevent foodborne disease.

PMID- 24919546
TI  - Left atrial appendage wall-motion velocity associates with recurrence of
      nonparoxysmal atrial fibrillation after catheter ablation.
AB  - Catheter ablation (CA) for nonparoxysmal atrial fibrillation (AF) is
      controversial due to its high recurrence rate. The aim of this study was to
      assess retrospectively the diagnostic value of preprocedural left atrial
      appendage (LAA) wall-motion velocity in predicting recurrence of AF within 1 year
      after CA. We hypothesized that tissue Doppler-derived measurement of LAA wall
      motion velocity associate with recurrence of AF within 1 year after CA. We
      retrospectively reviewed 47 consecutive patients with nonparoxysmal AF (defined
      as AF lasting for 1 week or longer) who underwent both transthoracic and
      transesophageal echocardiography before their first treatment by CA in a single
      center. Forty-one patients aged 58 +/- 10 years were included, and variables
      predicting the recurrence of AF within 1 year after CA were evaluated. Seventeen
      patients (41%) developed recurrence of AF within 1 year after CA. Univariate
      analyses showed that preprocedural LAA upward wall-motion velocity at the apex
      assessed by transesophageal echocardiography was significantly lower in patients
      with recurrence of AF than those without recurrence (OR = 1.45, 95% CI: 1.13
      2.01, P = 0.009). Multivariate logistic analyses including other potential
      predictors (duration of AF, left ventricular ejection fraction, E-wave
      deceleration time, and left atrial wall-motion velocity) identified LAA upward
      wall-motion velocity at the apex as an independent predictor of outcome. These
      data suggest in patients with nonparoxysmal AF, preprocedural LAA upward wall
      motion velocity at the apex, as determined by tissue Doppler imaging during
      transesophageal echocardiography, may be a useful indicator for predicting
      recurrence of AF within 1 year after CA.

PMID- 24919547
TI  - Buccal microRNA dysregulation in lung field carcinogenesis: gender-specific
      implications.
AB  - MicroRNAs (miRNAs) have been shown to be reliable early biomarkers in a variety
      of cancers including that of lung. We ascertained whether the biomarker potential
      of miRNAs could be validated in microscopically normal and easily accessible
      buccal epithelial brushings from cigarette smokers as a consequence of lung
      cancer linked 'field carcinogenesis'. We found that compared to neoplasia-free
      subjects, a panel of 68 miRNAs were upregulated and 3 downregulated in the normal
      appearing buccal mucosal cells collected from patients harboring lung cancer
      (n=76). The performance characteristics of selected miRNAs (with >= 1-fold
      change) were excellent with an average under the receiver operator characteristic
      curve (AUROC) of >0.80. Several miRNAs also displayed gender specificity between
      the groups. These results provide the first proof-of-concept scenario in which
      minimally intrusive cheek brushings could provide an initial screening tool in a
      large at-risk population.

PMID- 24919549
TI  - Force microscopy of layering and friction in an ionic liquid.
AB  - The mechanical properties of the ionic liquid 1-butyl-1-methylpyrrolidinium
      tris(pentafluoroethyl) trifluorophosphate ([Py1,4][FAP]) in confinement between a
      SiOx and a Au(1 1 1) surface are investigated by means of atomic force microscopy
      (AFM) under electrochemical control. Up to 12 layers of ion pairs can be detected
      through force measurements while approaching the tip of the AFM to the surface.
      The particular shape of the force versus distance curve is explained by a model
      for the interaction between tip, gold surface and ionic liquid, which assumes an
      exponentially decaying oscillatory force originating from bulk liquid density
      correlations. Jumps in the tip-sample distance upon approach correspond to jumps
      of the compliant force sensor between branches of the oscillatory force curve.
      Frictional force between the laterally moving tip and the surface is detected
      only after partial penetration of the last double layer between tip and surface.

PMID- 24919550
TI  - Female sexual dysfunction across the three pregnancy trimesters: an Egyptian
      study.
AB  - Background Pregnancy is a special period in the life of women characterised by
      physical, hormonal and psychological changes that, in conjugation with social and
      cultural influences, could affect women's sexuality as well as couples' sexual
      relationships. This cross-sectional study aimed to evaluate female sexual
      dysfunction (FSD) among the three pregnancy trimesters. METHODS: A total of 300
      healthy heterosexual pregnant Egyptian women with stable marital relationships
      were included. The Female Sexual Function Index (FSFI) questionnaire was used as
      a standard method for measuring female sexual function in each pregnancy
      trimester. RESULTS: There was no significant relationship between FSD and women's
      education, work, gravidity and parity. The incidence of FSD demonstrated
      significant alterations throughout pregnancy, being 68% in the first trimester,
      decreasing in the second trimester to 51% and increasing to 72% in the third
      trimester. Sexual desire decreased in the first trimester, was variable in the
      second trimester and decreased at the end of the third trimester (3.5+/-1.2,
      3.7+/-1.2 and 3.4+/-1.1 respectively). Sexual satisfaction declined significantly
      in the first trimester compared with the second and the third trimesters (4.2+/
      1.1, 4.8+/-0.8 and 4.6+/-1.0 respectively). Scores for the arousal, lubrication
      and orgasm domains were significantly decreased in the third trimester, where
      pain was increased in the second trimester compared with the first and third
      trimesters. CONCLUSION: Female sexual function is affected during pregnancy, with
      a significant change in all Female Sexual Function Index domains, especially in
      the first and third trimesters.

PMID- 24919548
TI  - Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4+ T cell
      effector functions.
AB  - Members of the evolutionarily conserved family of the chicken ovalbumin upstream
      promoter transcription factor NR2F/COUP-TF orphan receptors have been implicated
      in lymphocyte biology, ranging from activation to differentiation and elicitation
      of immune effector functions. In particular, a CD4+ T cell intrinsic and non
      redundant function of NR2F6 as a potent and selective repressor of the
      transcription of the pro-inflammatory cytokines interleukin (Il) 2, interferon y
      (ifng) and consequently of T helper (Th)17 CD4+ T cell-mediated autoimmune
      disorders has been discovered. NR2F6 serves as an antigen receptor signaling
      threshold-regulated barrier against autoimmunity where NR2F6 is part of a
      negative feedback loop that limits inflammatory tissue damage induced by weakly
      immunogenic antigens such as self-antigens. Under such low affinity antigen
      receptor stimulation, NR2F6 appears as a prototypical repressor that functions to
      "lock out" harmful Th17 lineage effector transcription. Mechanistically, only
      sustained high affinity antigen receptor-induced protein kinase C (PKC)-mediated
      phosphorylation has been shown to inactivate NR2F6, thereby displacing pre-bound
      NR2F6 from the DNA and, subsequently, allowing for robust NFAT/AP-1- and
      RORgammat-mediated cytokine transcription. The NR2F6 target gene repertoire thus
      identifies a general anti-inflammatory gatekeeper role for this orphan receptor.
      Investigating these signaling pathway(s) will enable a greater knowledge of the
      genetic, immune, and environmental mechanisms that lead to chronic inflammation
      and of certain autoimmune disorders in a given individual. 

PMID- 24919551
TI  - [Effect of ghrelin on colonic motility].

PMID- 24919552
TI  - [Emerging role of interleukin-19 as an inflammatory mediator in inflammatory
      bowel disease].

PMID- 24919553
TI  - [Role of inflammatory cytokine TNF-alpha and microenvironment in mouse gastric
      tumorigenesis].

PMID- 24919554
TI  - [Cross-talk through ATP in the vascular system].

PMID- 24919555
TI  - [Mechanisms for the differentiation of postnatal and adult neural stem cells: new
      insights and pathological issues based on the analysis of Girdin].

PMID- 24919556
TI  - [Open innovation hub in AIST].

PMID- 24919557
TI  - [Pharmacological profile and clinical evidence in patients with primary
      osteoporosis treated with intravenous ibandronate].

PMID- 24919558
TI  - [Novel feature of the HSP70 family].

PMID- 24919559
TI  - [Aiming to overcome ALS - the biomarkers for ALS].

PMID- 24919560
TI  - [Are glial cells involved in functional hyperemia in the brain?].

PMID- 24919561
TI  - Return to work of workers without a permanent employment contract, sick-listed
      due to a common mental disorder: design of a randomised controlled trial.
AB  - BACKGROUND: Workers without a permanent employment contract represent a
      vulnerable group within the working population. Mental disorders are a major
      cause of sickness absence within this group. Common mental disorders are stress
      related, depressive and anxiety disorders. To date, little attention has been
      paid to effective return to work interventions for this type of sick-listed
      workers. Therefore, a participatory supportive return to work program has been
      developed. It combines elements of a participatory return to work program,
      integrated care and direct placement in a competitive job.The objective of this
      paper is to describe the design of a randomised controlled trial to evaluate the
      cost-effectiveness of this program compared to care as usual. METHODS/DESIGN: The
      cost-effectiveness of the participatory supportive return to work program will be
      examined in a randomised controlled trial with a follow-up of twelve months.The
      program strongly involves the sick-listed worker in the identification of
      obstacles for return to work and possible solutions, resulting in a consensus
      based action plan. This plan will be used as a starting point for the search of
      suitable competitive employment with support of a rehabilitation agency. During
      this process the insurance physician of the sick-listed worker contacts other
      caregivers to promote integrated care.Workers eligible to participate in this
      study have no permanent employment contract, have applied for a sickness benefit
      at the Dutch Social Security Agency and are sick-listed between two and fourteen
      weeks due to mental health problems.The primary outcome measure is the duration
      until first sustainable return to work in a competitive job. Outcomes are
      measured at baseline and after three, six, nine and twelve months. DISCUSSION: If
      the participatory supportive return to work program proves to be cost-effective,
      the social security system, the sick-listed worker and society as a whole will
      benefit. A cost-effective return to work program will lead to a reduction of
      costs related to sickness absence. For the sick-listed worker a cost-effective
      program results in earlier sustainable return to work, which can be associated
      with both social and health benefits. TRIAL REGISTRATION: The trial registration
      number and date is NTR3563, August 7, 2012.

PMID- 24919562
TI  - Cholesterol embolization syndrome with an atypical proximal presentation
      simulating calciphylaxis.

PMID- 24919563
TI  - Phosphorescent sensor for phosphorylated peptides based on an iridium complex.
AB  - A bis[(4,6-difluorophenyl)pyridinato-N,C(2')]iridium(III) picolinate (FIrpic)
      derivative coupled with bis(Zn(2+)-dipicolylamine) (ZnDPA) was developed as a
      sensor (1) for phosphorylated peptides, which are related to many cellular
      mechanisms. As a control, a fluorescent sensor (2) based on anthracene coupled to
      ZnDPA was also prepared. When the total negative charge on the phosphorylated
      peptides was changed to -2, -4, and -6, the emission intensity of sensor 1
      gradually increased by factors of up to 7, 11, and 16, respectively. In contrast,
      there was little change in the emission intensity of sensor 1 upon the addition
      of a neutral phosphorylated peptide, non-phosphorylated peptides, or various
      anions such as CO3(2-), NO3(-), SO4(2-), phosphate, azide, and pyrophosphate.
      Furthermore, sensor 1 could be used to visually discriminate between
      phosphorylated peptides and adenosine triphosphate in aqueous solution under a UV
      vis lamp, unlike fluorescent sensor 2. This enhanced luminance of phosphorescent
      sensor 1 upon binding to a phosphorylated peptide is attributed to a reduction in
      the repulsion between the Zn(2+) ions due to the phenoxy anion, its strong metal
      to-ligand charge transfer character, and a reduction in self-quenching. 

PMID- 24919564
TI  - From trial to population: a study of a family-based community intervention for
      childhood overweight implemented at scale.
AB  - OBJECTIVES: To assess how outcomes associated with participation in a family
      based weight management intervention (MEND 7-13, Mind, Exercise, Nutrition..Do
      it!) for childhood overweight or obesity implemented at scale in the community
      vary by child, family, neighbourhood and MEND programme characteristics.
      METHODS/SUBJECTS: Intervention evaluation using prospective service level data.
      Families (N=21,132) with overweight children are referred, or self-refer, to
      MEND. Families (participating child and one parent/carer) attend two
      sessions/week for 10 weeks (N=13,998; N=9563 with complete data from 1788
      programmes across England). Sessions address diet and physical activity through
      education, skills training and motivational enhancement. MEND was shown to be
      effective in obese children in a randomised controlled trial (RCT). Outcomes were
      mean change in body mass index (BMI), age- and sex-standardised BMI (zBMI), self
      esteem (Rosenberg scale) and psychological distress (Strengths and Difficulties
      Questionnaire) after the 10-week programme. Relationships between the outcome and
      covariates were tested in multilevel models adjusted for the outcome at baseline.
      RESULTS: After adjustment for covariates, BMI reduced by mean 0.76 kg m(-2)
      (s.e.=0.021, P<0.0001), zBMI reduced by mean 0.18 (s.e.=0.0038, P<0.0001), self
      esteem score increased by 3.53 U  (s.e.=0.13, P<0.0001) and psychological
      distress score decreased by 2.65 U (s.e.=0.31, P<0.0001). Change in outcomes
      varied by participant, family, neighbourhood and programme factors. Generally,
      outcomes improved less among children from less advantaged backgrounds and in
      Asian compared with white children. BMI reduction under service conditions was
      slightly but not statistically significantly less than in the earlier RCT.
      CONCLUSIONS: The MEND intervention, when delivered at scale, is associated with
      improved BMI and psychosocial outcomes on average, but may work less well for
      some groups of children, and so has the potential to widen inequalities in these
      outcomes. Such public health interventions should be implemented to achieve
      sustained impact for all groups.

PMID- 24919565
TI  - Changes in morphology and function of adrenal cortex in mice fed a high-fat diet.
AB  - BACKGROUND/OBJECTIVES: Obesity is a major risk factor for the development of type
      2 diabetes and other debilitating diseases. Obesity and diabetes are intimately
      linked with altered levels of adrenal steroids. Elevated levels of these hormones
      induce insulin resistance and cause cardiovascular diseases. The mechanisms
      underlying obesity-related alterations in adrenal steroids are still not well
      understood. Here, we investigated how diet-induced obesity affects the morphology
      and function of the mouse adrenal cortex. METHODS: We fed animals either a high
      fat diet (HFD) or a normal diet (60% kcal from fat or 10% kcal from fat,
      respectively) for 18 weeks. We then assessed various aspects of adrenal gland
      morphology and function, as well as basal plasma concentrations of steroid
      hormones and ACTH. RESULTS: We show that adrenal glands of mice fed a HFD release
      more corticosterone and aldosterone, resulting in higher plasma levels. This
      increase is driven by adrenal cortical hyperplasia, and by increased expression
      of multiple genes involved in steroidogenesis. We demonstrate that diet-induced
      obesity elevates Sonic hedgehog signaling in Gli1-positive progenitors, which
      populate the adrenal capsule and give rise to the steroidogenic cells of the
      adrenal cortex. Feeding animals with a HFD depletes Gli1-positive progenitors, as
      the adrenal cortex expands. CONCLUSIONS: This work provides insight into how diet
      induced obesity changes the biology of the adrenal gland. The association of
      these changes with increased Shh signaling suggests possible therapeutic
      strategies for obesity-related steroid hormone dysfunction.

PMID- 24919566
TI  - SWIFT MRI enhances detection of breast cancer metastasis to the lung.
AB  - PURPOSE: To evaluate the capability of longitudinal MR scans using sweep imaging
      with Fourier transformation (SWIFT) to detect breast cancer metastasis to the
      lung in mice. METHODS: Mice with breast cancer metastatic to the lung were
      generated by tail vein injection of MDA-MB-231-LM2 cells. Thereafter, MR imaging
      was performed every week using three different pulse sequences: SWIFT [echo time
      (TE) ~3 MUs], concurrent dephasing and excitation (CODE; TE ~300 MUs), and three
      dimensional (3D) gradient echo (GRE; TE = 2.2 ms). Motion during the long SWIFT
      MR scans was compensated for by rigid-body motion correction. Maximum intensity
      projection (MIP) images were generated to visualize changes in lung vascular
      structures during the development and growth of metastases. RESULTS: SWIFT MRI
      was more sensitive to signals from the lung parenchyma than CODE or 3D GRE MRI.
      Metastatic tumor growth in the lungs induced a progressive increase in intensity
      of parenchymal signals in SWIFT images. MIP images from SWIFT clearly visualized
      lung vascular structures and their disruption due to progression of breast cancer
      metastases in the lung. CONCLUSION: SWIFT MRI's sensitivity to fast-decaying
      signals and tolerance of magnetic susceptibility enhances its effectiveness at
      detecting structural changes in lung parenchyma and vasculature due to breast
      cancer metastases in the lung.

PMID- 24919567
TI  - Catalytic zinc complexes for phosphate diester hydrolysis.
AB  - Creating efficient artificial catalysts that can compete with biocatalysis has
      been an enduring challenge which has yet to be met. Reported herein is the
      synthesis and characterization of a series of zinc complexes designed to catalyze
      the hydrolysis of phosphate diesters. By introducing a hydrated aldehyde into the
      ligand we achieve turnover for DNA-like substrates which, combined with ligand
      methylation, increases reactivity by two orders of magnitude. In contrast to
      current orthodoxy and mechanistic explanations, we propose a mechanism where the
      nucleophile is not coordinated to the metal ion, but involves a tautomer with a
      more effective Lewis acid and more reactive nucleophile. This data suggests a new
      strategy for creating more efficient metal ion based catalysts, and highlights a
      possible mode of action for metalloenzymes. 

PMID- 24919568
TI  - Skin barrier dysfunction and low antimicrobial peptide expression in cutaneous T
      cell lymphoma.
AB  - PURPOSE: Atopic dermatitis is characterized by decreased expression of filaggrin
      and loricrin. Patients with atopic dermatitis often suffer from skin infections,
      which are also frequently seen in patients with cutaneous T-cell lymphoma (CTCL).
      In this study, we aimed to investigate the skin barrier in CTCL. EXPERIMENTAL
      DESIGN: We assessed skin moisture and transepidermal water loss (TEWL) in
      patients with CTCL. We next examined mRNA expression levels of filaggrin,
      loricrin, and antimicrobial peptides (AMP) in skin samples of CTCL, using skin
      from healthy volunteers and patients with atopic dermatitis or psoriasis as
      controls. Immunostainings for filaggrin, loricrin, and S100 proteins were also
      performed. RESULTS: Lower levels of skin moisture accompanied by higher levels of
      TEWL were seen in lesional skin of CTCL than in normal skin. CTCL lesional skin
      contained lower levels of filaggrin and loricrin mRNA than normal skin, which was
      also true with atopic dermatitis and psoriatic skin. mRNA expression levels of
      filaggrin in CTCL skin negatively correlated with disease severity markers.
      Expression levels of AMPs in lesional skin of CTCL and atopic dermatitis were
      significantly lower than in psoriatic skin. Immunohistochemistry confirmed
      decreased expression of filaggrin and loricrin in CTCL, atopic dermatitis, and
      psoriatic skin and enhanced expression of S100 proteins in psoriatic skin.
      CONCLUSIONS: Our results show that there is barrier dysfunction in CTCL skin,
      similar to what is seen with atopic dermatitis skin. In addition, low AMP
      expression in CTCL skin was documented when compared with psoriatic skin, which
      may explain frequent infections that can occur in patients with CTCL.

PMID- 24919571
TI  - Hepatic uptake transporters and docetaxel disposition in mice-letter.

PMID- 24919570
TI  - To "grow" or "go": TMEM16A expression as a switch between tumor growth and
      metastasis in SCCHN.
AB  - PURPOSE: Tumor metastasis is the leading cause of death in patients with cancer.
      However, the mechanisms that underlie metastatic progression remain unclear. We
      examined TMEM16A (ANO1) expression as a key factor shifting tumors between growth
      and metastasis. EXPERIMENTAL DESIGN: We evaluated 26 pairs of primary and
      metastatic lymph node (LN) tissue from patients with squamous cell carcinoma of
      the head and neck (SCCHN) for differential expression of TMEM16A. In addition, we
      identified mechanisms by which TMEM16A expression influences tumor cell motility
      via proteomic screens of cell lines and in vivo mouse studies of metastasis.
      RESULTS: Compared with primary tumors, TMEM16A expression decreases in metastatic
      LNs of patients with SCCHN. Stable reduction of TMEM16A expression enhances cell
      motility and increases metastases while decreasing tumor proliferation in an
      orthotopic mouse model. Evaluation of human tumor tissues suggests an epigenetic
      mechanism for decreasing TMEM16A expression through promoter methylation that
      correlated with a transition between an epithelial and a mesenchymal phenotype.
      These effects of TMEM16A expression on tumor cell size and epithelial-to
      mesenchymal transition (EMT) required the amino acid residue serine 970 (S970);
      however, mutation of S970 to alanine does not disrupt the proliferative
      advantages of TMEM16A overexpression. Furthermore, S970 mediates the association
      of TMEM16A with Radixin, an actin-scaffolding protein implicated in EMT.
      CONCLUSIONS: Together, our results identify TMEM16A, an eight transmembrane
      domain Ca2+-activated Cl- channel, as a primary driver of the "Grow" or "Go"
      model for cancer progression, in which TMEM16A expression acts to balance tumor
      proliferation and metastasis via its promoter methylation.

PMID- 24919569
TI  - Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus
      panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer.
AB  - PURPOSE: Panitumumab, a fully human anti-epidermal growth factor receptor
      monoclonal antibody (mAb), has demonstrated efficacy in patients with wild-type
      KRAS metastatic colorectal cancer (mCRC). Rilotumumab and ganitumab are
      investigational, fully human mAbs against hepatocyte growth factor (HGF)/scatter
      factor and IGF1R, respectively. Here we evaluate combining rilotumumab or
      ganitumab with panitumumab in previously treated patients with wild-type KRAS
      mCRC. EXPERIMENTAL DESIGN: Part 1 was a phase Ib dose-finding study of
      panitumumab plus rilotumumab. The primary endpoint was the incidence of dose
      limiting toxicities (DLT). Part 2 was a randomized phase II trial of panitumumab
      in combination with rilotumumab, ganitumab, or placebo. The primary endpoint was
      objective response rate (ORR); safety, progression-free survival (PFS), and
      overall survival (OS) were secondary endpoints. Archival tissue specimens were
      collected for exploratory correlative work. RESULTS: In part 1, no DLTs were
      reported. A recommended phase II dose of 10 mg/kg rilotumumab was selected. In
      part 2, for the panitumumab plus rilotumumab (n = 48), panitumumab plus ganitumab
      (n = 46), and panitumumab plus placebo arms (n = 48), the ORRs were 31%, 22%, and
      21%, respectively. The median PFS was 5.2, 5.3, and 3.7 months and median OS
      13.8, 10.6, and 11.6 months, respectively. Adverse events were tolerable.
      Exploratory biomarker analyses, including MET and IGF-related protein expression,
      failed to indicate conclusive predictive evidence on efficacy endpoints.
      CONCLUSIONS: Panitumumab plus rilotumumab met the prespecified criterion for
      improvement in ORR whereas ganitumab did not. This is the first study to suggest
      a benefit for combining an HGF inhibitor (rilotumumab) with panitumumab in
      previously treated patients with wild-type KRAS mCRC.

PMID- 24919572
TI  - Molecular testing for lymph node metastases as a determinant of colon cancer
      recurrence: results from a retrospective multicenter study.
AB  - PURPOSE: Recurrence risk assessment to make treatment decisions for early-stage
      colon cancer patients is a major unmet medical need. The aim of this
      retrospective multicenter study was to evaluate the clinical utility of guanylyl
      cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence. METHODS:
      The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463
      untreated T3N0 patients, blinded to clinical outcomes. One site's (n = 97) tissue
      grossing method precluded appropriate lymph node assessment resulting in post hoc
      exclusion. Cox regression models tested the relationship between GCC and the
      primary endpoint of time to recurrence. Assay methods, primary analyses, and cut
      points were all prespecified. RESULTS: Final dataset contained 366 patients, 38
      (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes
      was significantly associated with risk of recurrence [hazard ratio (HR) = 2.46,
      95% confidence interval (CI), 1.07-5.69, P = 0.035], whereas binary GCC LNR risk
      class (HR = 1.87, 95% CI, 0.99-3.54, P = 0.054) and mismatch repair (MMR) status
      (HR = 0.77, 95% CI, 0.36-1.62, P = 0.49) were not. In a secondary analysis using
      a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate
      (0.10 < LNR <= 0.20), and low (LNR <= 0.10), high-risk patients had a 2.5 times
      higher recurrence risk compared with low-risk patients (HR = 2.53, 95% CI, 1.24
      5.17, P = 0.011). CONCLUSIONS: GCC status is a promising prognostic factor
      independent of traditional histopathology risk factors in a contemporary
      population of patients with stage IIa colon cancer not treated with adjuvant
      therapy, but GCC determination must be performed with methodology adapted to the
      tissue procurement and fixation technique.

PMID- 24919574
TI  - CARTs on the road for myeloma.
AB  - Chimeric antigen receptors redirect T cells to surface antigens. Discovery and
      validation of appropriate target antigens expands the possible indications for
      chimeric-antigen receptor (CAR) T cells. CS1 is expressed at high levels by
      multiple myeloma cells, but also to some extent on other lymphocytes. CS1 may be
      a viable target for CAR T cells in multiple myeloma.

PMID- 24919573
TI  - Multifactorial T-cell hypofunction that is reversible can limit the efficacy of
      chimeric antigen receptor-transduced human T cells in solid tumors.
AB  - PURPOSE: Immunotherapy using vaccines or adoptively transferred tumor
      infiltrating lymphocytes (TIL) is limited by T-cell functional inactivation
      within the solid tumor microenvironment. The purpose of this study was to
      determine whether a similar tumor-induced inhibition occurred with genetically
      modified cytotoxic T cells expressing chimeric antigen receptors (CAR) targeting
      tumor-associated antigens. EXPERIMENTAL DESIGN: Human T cells expressing CAR
      targeting mesothelin or fibroblast activation protein and containing CD3zeta and
      4-1BB cytoplasmic domains were intravenously injected into immunodeficient mice
      bearing large, established human mesothelin-expressing flank tumors. CAR TILs
      were isolated from tumors at various time points and evaluated for effector
      functions and status of inhibitory pathways. RESULTS: CAR T cells were able to
      traffic into tumors with varying efficiency and proliferate. They were able to
      slow tumor growth, but did not cause regressions or cures. The CAR TILs underwent
      rapid loss of functional activity that limited their therapeutic efficacy. This
      hypofunction was reversible when the T cells were isolated away from the tumor.
      The cause of the hypofunction seemed to be multifactorial and was associated with
      upregulation of intrinsic T-cell inhibitory enzymes (diacylglycerol kinase and
      SHP-1) and the expression of surface inhibitory receptors (PD1, LAG3, TIM3, and
      2B4). CONCLUSIONS: Advanced-generation human CAR T cells are reversibly
      inactivated within the solid tumor microenvironment of some tumors by multiple
      mechanisms. The model described here will be an important tool for testing T cell
      based strategies or systemic approaches to overcome this tumor-induced
      inhibition. Our results suggest that PD1 pathway antagonism may augment human CAR
      T-cell function.

PMID- 24919576
TI  - Coupled near- and far-field scattering in silver nanoparticles for high
      efficiency, stable, and thin plasmonic dye-sensitized solar cells.
AB  - Here, we report plasmonically enhanced thin dye-sensitized solar cells (DSSCs) in
      an imidazolium-dicyanamide based ionic liquid, in which size-controlled metal
      (silver) nanoparticles (AgNPs) with passivation layers of a few nanometers are
      arranged into the electrolyte and photo-electrodes. It was revealed that the
      AgNPs in the electrolyte and the photo-electrode have distinct effects on device
      performance via different coupling mechanisms. Strong far-field scattering is
      critical in the electrolyte while near-field scattering is efficient in the photo
      electrode. Indeed, we find that the power conversion efficiency of the DSSC can
      be substantially improved by a synergistic arrangement of the AgNPs in the
      electrolyte and the photo-electrode. Furthermore, an imidazolium-dicyanamide
      based nonvolatile ionic liquid electrolyte for MNPs is demonstrated to provide
      thin plasmonic DSSCs with good stability. 

PMID- 24919575
TI  - Tyrosine phosphoproteomics identifies both codrivers and cotargeting strategies
      for T790M-related EGFR-TKI resistance in non-small cell lung cancer.
AB  - PURPOSE: Irreversible EGFR-tyrosine kinase inhibitors (TKI) are thought to be one
      strategy to overcome EGFR-TKI resistance induced by T790M gatekeeper mutations in
      non-small cell lung cancer (NSCLC), yet they display limited clinical efficacy.
      We hypothesized that additional resistance mechanisms that cooperate with T790M
      could be identified by profiling tyrosine phosphorylation in NSCLC cells with
      acquired resistance to reversible EGFR-TKI and harboring T790M. EXPERIMENTAL
      DESIGN: We profiled PC9 cells with TKI-sensitive EGFR mutation and paired EGFR
      TKI-resistant PC9GR (gefitinib-resistant) cells with T790M using immunoaffinity
      purification of tyrosine-phosphorylated peptides and mass spectrometry-based
      identification/quantification. Profiles of erlotinib perturbations were examined.
      RESULTS: We observed a large fraction of the tyrosine phosphoproteome was more
      abundant in PC9- and PC9GR-erlotinib-treated cells, including phosphopeptides
      corresponding to MET, IGF, and AXL signaling. Activation of these receptor
      tyrosine kinases by growth factors could protect PC9GR cells against the
      irreversible EGFR-TKI afatinib. We identified a Src family kinase (SFK) network
      as EGFR-independent and confirmed that neither erlotinib nor afatinib affected
      Src phosphorylation at the activation site. The SFK inhibitor dasatinib plus
      afatinib abolished Src phosphorylation and completely suppressed downstream
      phosphorylated Akt and Erk. Dasatinib further enhanced antitumor activity of
      afatinib or T790M-selective EGFR-TKI (WZ4006) in proliferation and apoptosis
      assays in multiple NSCLC cell lines with T790M-mediated resistance. This
      translated into tumor regression in PC9GR xenograft studies with combined
      afatinib and dasatinib. CONCLUSIONS: Our results identified both codrivers of
      resistance along with T790M and support further studies of irreversible or T790M
      selective EGFR inhibitors combined with dasatinib in patients with NSCLC with
      acquired T790M.

PMID- 24919578
TI  - Tolerability of ambulatory blood pressure monitoring (ABPM) in cognitively
      impaired elderly.
AB  - OBJECTIVE: Recent guidelines have widened clinical indications for out-of-office
      blood pressure measurement, including home blood pressure monitoring and
      ambulatory blood pressure monitoring (ABPM), suggesting the latter as recommended
      method in cognitively impaired patients. There is, however, a widespread belief
      that ABPM could be poorly tolerated in dementia, often leading to withdraw from
      its use in these patients. AIM: To assess the actual tolerability of ABPM in a
      group of cognitively impaired elderly, affected by dementia or mild cognitive
      impairment (MCI). METHODS: We evaluated 176 patients aged 65 + years, recruited
      in two different memory clinics, with a Mini Mental State Examination (MMSE)
      between 10 and 27. Behavioral and psychological symptoms were assessed with
      Neuropsychiatric Inventory (NPI). A patient was considered tolerant if able to
      keep the device on continuously for 24 h. The minimum number of correct
      measurements required was 70% of the predicted total number. RESULTS: 16% of
      patients wore the device for less than 24 h. Dividing the study population in
      tertiles of MMSE performance, 29% failed to tolerate the device in the lowest,
      12% in the middle and 7% in the highest tertile (p < 0.01). Dividing the study
      population in tertiles of NPI performance, 30% of patients failed in the highest,
      19% in the middle and 8% in the lowest tertile (p = 0.02); 31% of patients who
      tolerated the device did not achieve the minimum number of measurements required,
      with a mean number of 63% of predicted measurements. CONCLUSION: The ABPM proved
      a generally well-tolerated technique even in cognitively impaired elderly. Only a
      minority of subjects with poorer cognitive performances and greater behavioral
      symptoms did not tolerate the monitoring. Among most patients who failed to
      achieve the minimum number of measurements needed, the number of valid
      measurements was very close to the minimum required.

PMID- 24919577
TI  - A review of the pharmacological effects of piceatannol on cardiovascular
      diseases.
AB  - The incidence of cardiovascular diseases (CVDs) is high in both developed and
      developing countries. It has a high global rate of mortality and causes heavy
      social burden. Drugs are available for managing or treating CVDs and its
      complications. Consumption of dietary supplements or functional foods for
      reducing the risk of CVDs has also gained wide recognition by the general public.
      Piceatannol, an analog and metabolite of resveratrol, is a natural stilbene
      commonly found in the skin of grapes and wine. Piceatannol is believed to be a
      potent compound with certain cardiovascular therapeutic effects, such as the
      prevention of hypercholesterolemia, arrhythmia, atherosclerosis, and
      angiogenesis. It also has vasorelaxation and antioxidant activities. A
      comprehensive review of piceatannol concludes that piceatannol has the potential
      to be developed into health products for the cardiovascular system to help modern
      society reduce the high CVD incidence. However, further investigations are
      warranted in order to increase the bioavailability and understand the biological
      mechanisms and safety of using piceatannol.

PMID- 24919579
TI  - Replacement of highly conserved E222 by the photostable non-photoconvertible
      histidine in GFP.
AB  - The widely used green fluorescent protein (GFP) decarboxylates upon irradiation;
      this involves removal of the acidic function of the glutamic acid at position
      222, thereby resulting in the irreversible photoconversion of GFP. To suppress
      this phenomenon, the photostable, non-photoconvertible histidine was introduced
      at position 222 in GFP. The variant E222H shows negligible photodynamic processes
      and high expression yield. In addition, the stable and bright fluorescence over a
      wide pH range makes the E222H protein an alternative for GFP in fluorescence
      imaging and spectroscopy. Other fluorescent proteins are predicted to benefit
      from replacement of the catalytic glutamic acid by histidine. 

PMID- 24919580
TI  - A pollen-specific calmodulin-binding protein, NPG1, interacts with putative
      pectate lyases.
AB  - Previous genetic studies have revealed that a pollen-specific calmodulin-binding
      protein, No Pollen Germination 1 (NPG1), is required for pollen germination.
      However, its mode of action is unknown. Here we report direct interaction of NPG1
      with pectate lyase-like proteins (PLLs). A truncated form of AtNPG1 lacking the N
      terminal tetratricopeptide repeat 1 (TPR1) failed to interact with PLLs,
      suggesting that it is essential for NPG1 interaction with PLLs. Localization
      studies with AtNPG1 fused to a fluorescent reporter driven by its native promoter
      revealed its presence in the cytosol and cell wall of the pollen grain and the
      growing pollen tube of plasmolyzed pollen. Together, our data suggest that the
      function of NPG1 in regulating pollen germination is mediated through its
      interaction with PLLs, which may modify the pollen cell wall and regulate pollen
      tube emergence and growth. 

PMID- 24919581
TI  - Development of a sutureless dural substitute from Bombyx mori silk fibroin.
AB  - Silk solvent casting, electrospinning, and electrogelation techniques were used
      to create a biodegradable, biocompatible silk fibroin dural substitute. The all
      silk system was designed and produced to improve on currently available
      materials, grafts and tissue sealants used for dural closure in neurosurgery. The
      silk biomaterial was successfully fabricated as a dual layer adhesive system
      designed to seal durotomies while also functioning as a dural regeneration
      scaffold. The mechanical characteristics, biocompatibility, biodegradability, and
      hydrodynamic sealing capability of the material were evaluated. Results showed
      that the biomaterial was biocompatible with neural cells and fibroblasts, had
      mechanical properties mimicking the natural dura, was biodegradable with
      controllable degradation, and was able to seal against a hydrodynamic pressure of
      205 mmHg, which greatly exceeds the maximum cerebrospinal fluid pressure seen in
      both cranial and spinal dural closures of 50 mmHg. Based on its design and
      experimental results, the adhesive silk dual layer composite biomaterial shows
      potential as a sutureless dural repair system that would improve on current dural
      closure techniques.

PMID- 24919582
TI  - The adsorption and simulated separation of light hydrocarbons in isoreticular
      metal-organic frameworks based on dendritic ligands with different aliphatic side
      chains.
AB  - Three isoreticular metal-organic frameworks, JUC-100, JUC-103 and JUC-106, were
      synthesized by connecting six-node dendritic ligands to a [Zn4O(CO2)6] cluster.
      JUC-103 and JUC-106 have additional methyl and ethyl groups, respectively, in the
      pores with respect to JUC-100. The uptake measurements of the three MOFs for CH4,
      C2H4, C2H6 and C3H8 were carried out. At 298 K, 1 atm, JUC-103 has relatively
      high CH4 uptake, but JUC-100 is the best at 273 K, 1 atm. JUC-100 and JUC-103
      have similar C2H4 absorption ability. In addition, JUC-100 has the best
      absorption capacity for C2H6 and C3H8. These results suggest that high surface
      area and appropriate pore size are important factors for gas uptake. Furthermore,
      ideal adsorbed solution theory (IAST) analyses show that all three MOFs have good
      C3H8/CH4 and C2H6/CH4 selectivities for an equimolar quaternary
      CH4/C2H4/C2H6/C3H8 gas mixture maintained at isothermal conditions at 298 K, and
      JUC-106 has the best C2H6/CH4 selectivity. The breakthrough simulations indicate
      that all three MOFs have good capability for separating C2 hydrocarbons from C3
      hydrocarbons. The pulse chromatographic simulations also indicate that all three
      MOFs are able to separate CH4/C2 H4/C2H6/C3H8 mixture into three different
      fractions of C1, C2 and C3 hydrocarbons.

PMID- 24919583
TI  - Increased risk of cirrhosis and its decompensation in chronic hepatitis C
      patients with new-onset diabetes: a nationwide cohort study.
AB  - The effect of diabetes on cirrhosis, its decompensation, and their time
      relationship in chronic hepatitis C (CHC) patients remains unclear. We conducted
      a nation-wide cohort study by using the Taiwanese National Health Insurance
      Research Database, which is comprised of data from >99% of the entire population.
      Among having randomly sampled 1 million enrollees, 6,251 adult CHC patients were
      identified from 1997 to 2009. Diabetes was defined as new onset in CHC patients
      who were given the diagnosis in the years 1999-2003, but not in 1997-1998. The
      cohorts of CHC with new-onset diabetes (n=424) and nondiabetes (n=1,708) were
      followed up from inception point in diabetes and from year 1999 in the
      nondiabetes cohort until development of cirrhosis or its decompensation,
      withdrawal from insurance, or December 2009. Kaplan-Meier's survival analysis
      showed a significantly higher cumulative incidence of cirrhosis (relative risk
      [RR]=1.53; 95% confidence interval [CI]=1.11-2.11; log-rank test; P<0.001) and
      decompensated cirrhosis (RR=2.01; 95% CI=1.07-3.79; log-rank test; P<0.001) among
      patients with new-onset diabetes, as compared to those without. After adjustment
      for age, gender, CHC treatment, diabetes treatment, hepatocellular carcinoma,
      comorbidity index, hypertension, hyperlipidemia, and obesity by Cox's
      proportional hazard model, diabetes was still an independent predictor for
      cirrhosis (hazard ratio [HR]=2.505; 95% CI=1.609-3.897; P<0.001) and its
      decompensation (HR=3.560; 95% CI=1.526-8.307; P=0.003). CONCLUSION: CHC patients
      who develop diabetes are at an increased risk of liver cirrhosis and its
      decompensation over time.

PMID- 24919584
TI  - Oral anticoagulation and vitamin K deficiency.
AB  - A 61-year old woman with atrial fibrillation developed macrohaematuria during
      anticoagulant treatment with a direct oral factor Xa inhibitor for stroke
      prevention. Abnormal results of coagulation assays were first interpreted as an
      effect of the anticoagulant. However, upon further testing diagnosis of vitamin K
      deficiency was established. After vitamin K supplementation, coagulation tests
      normalized and macrohaematuria disappeared. Treatment with broad spectrum
      antibiotics for urinary tract infection was finally established as a rare cause
      for vitamin K deficiency in the patient. 

PMID- 24919585
TI  - Influence of nanostructure composition on its morphometric characterization by
      different techniques.
AB  - Morphometric characterization of nanoparticles is crucial to determine their
      biological effects and to obtain a formulation pattern. Determining the best
      technique requires knowledge of the particles being analyzed, the intended
      application of the particles, and the limitations of the techniques being
      considered. The aim of this article was to present transmission (TEM) and
      scanning (SEM) electron microscopy protocols for the analysis of two different
      nanostructures, namely polymeric nanoemulsion and poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles, and to compare these results with conventional dynamic
      light scattering (DLS) measurements. The mean hydrodynamic diameter, the
      polydispersity index, and zeta potential of the nanostructures of polymeric
      nanoemulsion were 370.5 +/- 0.8 nm, 0.133 +/- 0.01, and -36.1 +/- 0.15 mV,
      respectively, and for PLGA nanoparticles were 246.79 +/- 5.03 nm, 0.096 +/-
      0.025, and -4.94 +/- 0.86 mV, respectively. TEM analysis of polymeric
      nanoemulsion revealed a mean diameter of 374 +/- 117 nm. SEM analysis showed a
      mean diameter of 368 +/- 69 nm prior to gold coating and 448 +/- 70 nm after gold
      coating. PLGA nanoparticles had a diameter of 131 +/- 41.18 nm in TEM and 193 +/-
      101 nm in SEM. Morphologically, in TEM analysis, the polymeric nanoemulsions were
      spherical, with variable electron density, very few showing an electron-dense
      core and others an electron-dense surface. PLGA nanoparticles were round, with an
      electron-lucent core and electron-dense surface. In SEM, polymeric nanoemulsions
      were also spherical with a rough surface, and PLGA nanoparticles were round with
      a smooth surface. The results show that the "gold standards" for morphometric
      characterization of polymeric nanoemulsion and PLGA nanoparticles were,
      respectively, SEM without gold coating and TEM with negative staining.

PMID- 24919586
TI  - Fetal cardiac parameters for prediction of twin-to-twin transfusion syndrome.
AB  - OBJECTIVES: To assess myocardial performance index measured by conventional
      Doppler (MPI) and by tissue Doppler imaging (MPI') at 18 weeks' gestation in
      monochorionic diamniotic twins for the prediction of twin-to-twin transfusion
      syndrome (TTTS). METHODS: This was a single-center observational study of 100
      uncomplicated monochorionic diamniotic twin pregnancies attending the twin
      pregnancy clinic at the University Hospital Spedali Civili of Brescia from 2009
      to 2012. MPI and MPI' were obtained from the left (LV) and right (RV) ventricles
      of each twin at around 18 weeks of gestation (range, 17 + 1 to 19 + 4 weeks) and
      fortnightly thereafter. Cases which later developed TTTS formed the study group,
      and the remaining controls were subdivided into those continuing as uncomplicated
      pregnancies and those which later developed selective intrauterine growth
      restriction (sIUGR). Data were analyzed by receiver-operating characteristics
      curve analysis and univariate and multivariable logistic regression. RESULTS: Of
      the 100 pregnancies, 88 were controls (84 uncomplicated and four developed sIUGR)
      and 12 developed TTTS. RV-MPI and LV-MPI, and LV-MPI' were significantly higher
      in future TTTS recipients than in controls, while RV-MPI' was significantly lower
      in donors. RV-MPI and LV-MPI and LV-MPI' were found to be predictive indicators
      in pregnancies that had not yet developed TTTS. Their negative predictive values
      were > 90%, and their specificities > 80%. The best performing index was LV-MPI',
      with a sensitivity of 91.7% and specificity of 88.6%. CONCLUSIONS: Before
      diagnosis of TTTS, the cardiac function (as assessed by MPI and MPI') of the
      future donor twin is not grossly abnormal, but that of the recipient is abnormal.
      We identified cardiac indices predictive of the subsequent development of TTTS,
      and suggest a possible role of these indices in planning the follow-up of
      monochorionic diamniotic twin pregnancies.

PMID- 24919587
TI  - Effectiveness of phototherapy incorporated into an exercise program for
      osteoarthritis of the knee: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Osteoarthritis is a chronic disease with a multifactor etiology
      involving changes in bone alignment, cartilage, and other structures necessary to
      joint stability. There is a need to investigate therapeutic resources that
      combine different wavelengths as well as different light sources (low-level laser
      therapy and light-emitting diode therapy) in the same apparatus for the treatment
      of osteoarthritis. The aim of the proposed study is to analyze the effect of the
      incorporation of phototherapy into a therapeutic exercise program for individuals
      with osteoarthritis of the knee. METHODS/DESIGN: A double-blind, controlled,
      randomized clinical trial will be conducted involving patients with
      osteoarthritis of the knee. Evaluations will be performed using functional
      questionnaires before and after the treatment protocols, in a reserved room with
      only the evaluator and participant present, and no time constraints placed on the
      answers or evaluations. The following functional tests will also be performed:
      stabilometry (balance assessment), dynamometry (muscle strength of gluteus medius
      and quadriceps), algometry (pain threshold), fleximeter (range of motion), timed
      up-and-go test (functional mobility), and the functional reach test. The
      participants will then be allocated to three groups through a randomization
      process using opaque envelopes: exercise program, exercise program +
      phototherapy, or exercise program + placebo phototherapy, all of which will last
      for eight weeks. DISCUSSION: The purpose of this randomized clinical trial is to
      analyze the effect of the incorporation of phototherapy into a therapeutic
      exercise program for osteoarthritis of the knee. The study will support the
      practice based on evidence to the use of phototherapy in individuals with a
      diagnosis of osteoarthritis of the knee. Data will be published after the study
      is completed. TRIAL REGISTRATION: The protocol for this study has been submitted
      to Clinical Trials, registration number NCT02102347, on 29 March 2014.

PMID- 24919588
TI  - Minocycline and cisplatin exert synergistic growth suppression on hepatocellular
      carcinoma by inducing S phase arrest and apoptosis.
AB  - Minocycline, a semisynthetic tetracycline, is a highly lipophilic molecule
      capable of infiltrating tissues and blood. Previous studies have revealed the
      functions and mechanisms of minocycline in anti-inflammation, protection of the
      nervous system and certain tumors. The role of minocycline has never been
      investigated in hepatocellular carcinoma (HCC). The functions of minocycline on
      HCC cells were investigated using immunohistochemical staining and western
      blotting. Minocycline was applied to L02, HepG2 and Huh7 cells, and the growth
      characteristics were studied. Cisplatin was administered in combination with
      minocycline in this study. Cell cycle and apoptosis analyses were employed to
      investigate the mechanisms underlying the growth regulation associated with
      minocycline and(or) cisplatin. Minocycline caused S phase cell cycle arrest and
      an increase in the apoptotic rate associated with upregulation of p27, cleaved
      caspase8, cleaved-caspase3 and cleaved-PRAP-1. Low dose of cisplatin promoted
      cell cycle arrest and apoptosis, whereas minocycline was mainly associated with
      upregulation of cleaved-PARP-1. The combination of cisplatin and minocycline
      increased the rate and extent of cell cycle arrest and increased the apoptosis
      rate caused by minocycline. A novel mechanism was revealed. Minocycline functions
      as an antitumor drug in HCC by regulating p27, caspase-3 and PARP-1. Cisplatin
      enhanced minocycline's effect on PARP-1.

PMID- 24919589
TI  - Testicular histomorphologic and stereological alterations following short-term
      treatment with highly active antiretroviral drugs (HAART) in an experimental
      animal model.
AB  - The increased accessibility of antiretroviral therapy continues to positively
      drive the reduction in viral load and survival of patients despite the attendant
      reproductive toxicities. We propose that testicular damage caused by highly
      active antiretroviral therapy (HAART) can be attenuated by antioxidant treatment
      by investigating the testicular histomorphologic and stereological effects of
      antiretroviral drugs and its interaction with antioxidants using an experimental
      animal model. Sprague-Dawley rats were divided into seven groups of six rats per
      group (A, B... G) using simple random sampling and treated orally with 0.9%
      normal saline as placebo, a HAART cocktail of stavudine, lamivudine and
      nevirapine using the adjusted human therapeutic doses of 200, 600 and 350-400
      mg/day, respectively, and antioxidants ascorbic acid (vitamin C) and I.M alpha
      tocopherol (vitamin E). Animals were killed after 4 weeks and testicular tissue
      harvested and processed for light microscopy and stereological evaluations. The
      results were interpreted by a Veterinary pathologist blinded to the study. No
      animal died during the experimental period. The histopathological assessment of
      the testis of animals treated with placebo, ascorbic acid alone and alpha
      tocopherol alone as well as vitamin E + HAART displayed normal testicular
      microanatomy. Groups treated with HAART alone, HAART + vitamin C + vitamin E and
      vitamins C + HAART showed extensive seminiferous tubular atrophy, necrosis and
      hypocellularity in the histoarchitectural patterns. While testicular cross
      sectional area of seminiferous tubules remained unaffected by HAART, epithelial
      heights significantly decreased (p < 0.05) when compared with controls. There was
      marked (p < 0.05) increased in testicular-body weight ratio in HAART group. The
      results show that vitamin E could be useful in protecting testicular tissue from
      toxicities of HAART regimes as these results mirrors stereological data for the
      groups. HAART presents with deleterious histopathological changes in the testes
      causing tubular atrophy with altered morphometric indices. Supplementation with
      vitamin E appears to be a better adjuvant antioxidant that ameliorates these
      deleterious effects.

PMID- 24919591
TI  - Positive end-expiratory pressure (PEEP) during anaesthesia for prevention of
      mortality and postoperative pulmonary complications.
AB  - BACKGROUND: General anaesthesia causes atelectasis, which can lead to impaired
      respiratory function. Positive end-expiratory pressure (PEEP) is a mechanical
      manoeuvre that increases functional residual capacity (FRC) and prevents collapse
      of the airways, thereby reducing atelectasis. It is not known whether
      intraoperative PEEP alters the risks of postoperative mortality and pulmonary
      complications. This review was originally published in 2010 and was updated in
      2013. OBJECTIVES: To assess the benefits and harms of intraoperative PEEP in
      terms of postoperative mortality and pulmonary outcomes in all adult surgical
      patients. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) 2013, Issue 10, part of The Cochrane Library, as well as MEDLINE
      (via Ovid) (1966 to October 2013), EMBASE (via Ovid) (1980 to October 2013),
      CINAHL (via EBSCOhost) (1982 to October 2013), ISI Web of Science (1945 to
      October 2013) and LILACS (via BIREME interface) (1982 to October 2010). The
      original search was performed in January 2010. SELECTION CRITERIA: We included
      randomized clinical trials assessing the effects of PEEP versus no PEEP during
      general anaesthesia on postoperative mortality and postoperative respiratory
      complications in adults, 16 years of age and older. DATA COLLECTION AND ANALYSIS:
      Two review authors independently selected papers, assessed trial quality and
      extracted data. We contacted study authors to ask for additional information,
      when necessary. We calculated the number of additional participants needed
      (information size) to make reliable conclusions. MAIN RESULTS: This updated
      review includes two new randomized trials. In total, 10 randomized trials with
      432 participants and four comparisons are included in this review. One trial had
      a low risk of bias. No differences were demonstrated in mortality, with risk
      ratio (RR) of 0.97 (95% confidence interval (CI) 0.20 to 4.59; P value 0.97; 268
      participants, six trials, very low quality of evidence (grading of
      recommendations assessment, development and evaluation (GRADE)), and in
      pneumonia, with RR of 0.40 (95% CI 0.11 to 1.39; P value 0.15; 120 participants,
      three trials, very low quality of evidence (GRADE)). Statistically significant
      results included the following: The PEEP group had higher arterial oxygen
      pressure (PaO2)/fraction of inspired oxygen (FiO2) on day one postoperatively,
      with a mean difference of 22.98 (95% CI 4.40 to 41.55; P value 0.02; 80
      participants, two trials, very low quality of evidence (GRADE)), and
      postoperative atelectasis (defined as an area of collapsed lung, quantified by
      computerized tomography scan) was less in the PEEP group (standard mean
      difference -1.2, 95% CI -1.78 to -0.79; P value 0.00001; 88 participants, two
      trials, very low quality of evidence (GRADE)). No adverse events were reported in
      the three trials that adequately measured these outcomes (barotrauma and cardiac
      complications). Using information size calculations, we estimated that a further
      21,200 participants would have to be randomly assigned to allow a reliable
      conclusion about PEEP and mortality. AUTHORS' CONCLUSIONS: Evidence is currently
      insufficient to permit conclusions about whether intraoperative PEEP alters risks
      of postoperative mortality and respiratory complications among undifferentiated
      surgical patients.

PMID- 24919592
TI  - (13)C NMR investigations and the molecular order of 4-(trans-4'-hexylcyclohexyl)
      isothiocyanatobenzene (6CHBT).
AB  - The static 1D (13)C and 2D Proton Encoded Local Field (PELF) NMR experiments are
      carried out in the nematic phase of a less viscous liquid crystal 4-(trans-4'
      hexylcyclohexyl)-isothiocyanatobenzene (6CHBT) with a view to find orientational
      order. The PELF spectra provide better resolution which facilitates the
      assignment of cyclohexyl and phenyl ring carbons relatively easy. For the
      cyclohexyl unit, four pairs of dipolar splitting are clearly noticed in contrast
      to earlier reports on structurally similar mesogens where only two pairs of
      doublets are seen. The linear relationship between anisotropic chemical shifts
      and orientational order is established and semi-empirical parameters are obtained
      to aid the study of the order behaviour of 6CHBT over the entire nematic range.
      The data further fitted to the Haller equation and a reasonably good agreement is
      observed. The temperature dependence trends of orientational order parameters
      extracted for various carbons using (13)C-(1)H dipolar couplings with those of
      (13)C chemical shifts are compared. A gradual decrease in the order parameter is
      noticed for different molecular segments while traversing from the core to the
      aliphatic chain via the cyclohexyl ring. The notable decreasing trends of order
      parameters along the chain are observed similar to those of the corresponding
      phenyl cyclohexanes reported earlier. 

PMID- 24919593
TI  - Aberrant PTPRO methylation in tumor tissues as a potential biomarker that
      predicts clinical outcomes in breast cancer patients.
AB  - BACKGROUND: Aberrant hypermethylation of gene promoter regions is a primary
      mechanism by which tumor suppressor genes become inactivated in breast cancer.
      Epigenetic inactivation of the protein tyrosine phosphatase receptor-type O gene
      (PTPRO) has been described in several types of cancer. RESULTS: We screened
      primary breast cancer tissues for PTPRO promoter hypermethylation and assessed
      potential associations with pathological features and patient outcome. We also
      evaluated its potential as a breast cancer biomarker. PTPRO methylation was
      observed in 53 of 98 (54%) breast cancer tissues but not in adjacent normal
      tissue. Among matched peripheral blood samples from breast cancer patients, 33 of
      98 (34%) exhibited methylated PTPRO in plasma. In contrast, no methylated PTPRO
      was observed in normal peripheral blood from 30 healthy individuals. PTPRO
      methylation was positively associated with lymph node involvement (P = 0.014),
      poorly differentiated histology (P = 0.037), depth of invasion (P = 0.004), and
      HER2 amplification (P = 0.001). Multivariate analysis indicated that aberrant
      PTPRO methylation could serve as an independent predictor for overall survival
      hazard ratio (HR): 2.7; 95% CI: 1.1-6.2; P = 0.023), especially for patients with
      HER2-positive (hazard ratio (HR): 7.5; 95% CI: 1.8-31.3; P = 0.006), but not in
      ER + and PR + subpopulation. In addition, demethylation induced by 5-azacytidine
      led to gene reactivation in PTPRO-methylated and -silenced breast cancer cell
      lines. CONCLUSIONS: Here, we report that tumor PTPRO methylation is a strong
      prognostic factor in breast cancer. Methylation of PTPRO silences its expression
      and plays an important role in breast carcinogenesis. The data we present here
      may provide insight into the development of novel therapies for breast cancer
      treatment. Additionally, detection of PTPRO methylation in peripheral blood of
      breast cancer patients may provide a noninvasive means to diagnose and monitor
      the disease.

PMID- 24919594
TI  - Efficient diagnosis of Sjogren's syndrome to reduce the burden on patients.
AB  - OBJECTIVE: The purpose of this study was to investigate the procedures for
      efficiently diagnosing Sjogren's syndrome to reduce patient burden. METHODS: This
      study analyzed data from 254 Japanese patients diagnosed with Sjogren's syndrome
      out of 4967 who visited our clinic complaining of xerostomia. RESULTS: Of the 254
      Sjogren's syndrome patients, 140 fulfilled the criteria proposed by the Committee
      on Sjogren's Syndrome of the Ministry of Health and Welfare of Japan, 228
      fulfilled the criteria proposed by the American-European Consensus Group, and 69
      fulfilled the criteria proposed by the American College of Rheumatology. Numbers
      of definitive cases varied with each set of criteria. Logistic regression
      analysis was used to analyze useful examination items for definitive diagnosis of
      Sjogren's syndrome, demonstrating that anti-Ro/SSA (odds ratio (OR), 7.165), lip
      biopsy (OR, 4.273), sialography (OR, 2.402), and ANA (OR, 0.678) correlated
      significantly with definitive diagnosis of Sjogren's syndrome. CONCLUSIONS: These
      results suggest that the following diagnostic procedure for Sjogren's syndrome
      would reduce burden on patients. When clinicians choose examination items for
      diagnosing Sjogren's syndrome, they should first select which criteria to use.
      Then, to minimize the number of examination items, examinations should be
      performed in order of anti-SSA antibody, lip biopsy, and parotid gland
      sialography.

PMID- 24919595
TI  - High-resolution chromosomal microarrays in prenatal diagnosis significantly
      increase diagnostic power.
AB  - OBJECTIVE: The objective of this study was to determine for the first time the
      reliability and the diagnostic power of high-resolution microarray testing in
      routine prenatal diagnostics. METHODS: We applied high-resolution chromosomal
      microarray testing in 464 cytogenetically normal prenatal samples with any
      indication for invasive testing. RESULTS: High-resolution testing revealed a
      diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and
      cases of advanced maternal age (AMA), respectively, which is similar to previous
      studies using low-resolution microarrays. In three (0.6%) additional cases with
      an indication of AMA, an aberration in susceptibility risk loci was detected.
      Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a
      finding relevant for future family planning. We found the rate of cases, in which
      the parents had to be tested for interpretation of unreported copy number
      variants (3.7%), and the rate of remaining variants of unknown significance
      (0.4%) acceptably low. Of note, these findings did not cause termination of
      pregnancy after expert genetic counseling. The 0.4% rate of confined placental
      mosaicism was similar to that observed by conventional karyotyping and notably
      involved a case of placental microdeletion. CONCLUSION: High-resolution prenatal
      microarray testing is a reliable technique that increases diagnostic yield by at
      least 17.3% when compared with conventional karyotyping, without an increase in
      the frequency of variants of uncertain significance.

PMID- 24919596
TI  - Systemic lupus erythematosus: molecular cloning and analysis of recombinant DNase
      monoclonal kappa light chain NGK-1.
AB  - Because DNase antibodies are cytotoxic, enter the nucleus and cause DNA
      fragmentation inducing cell death by apoptosis, they can play an important role
      in the pathogenesis of different autoimmune pathologies and especially systemic
      lupus erythematosus (SLE). The interesting goal of catalytic antibodies research
      is not only to study a possible biological role of such antibodies, but also to
      develop in future new human and animal therapies that use the advantages offered
      by abzymes. An immunoglobulin kappa light chain library from SLE patients was
      cloned into a phagemid vector. Phage particles displaying recombinant monoclonal
      antibody light chains (MLChs) capable of binding DNA were isolated by affinity
      chromatography on DNA-cellulose. Sixteen of the 46 MLChs efficiently hydrolyzed
      DNA; one MLCh (approximately 27-28kDa) was expressed in Escherichia coli and
      purified by metal chelating and gel filtration. MLCh NGK-1 was
      electrophoretically homogeneous and demonstrated a positive answer with mouse
      IgGs against light chains of human antibodies after western blotting. SDS-PAGE in
      a gel containing DNA demonstrated that the MLCh hydrolyzes DNA and is not
      contaminated by canonical DNases. The DNase MLCh was activated by several metal
      ions. The protein sequence of the DNase MLCh has homology with mammalian DNases I
      and shares with them several identical or similar (with the same side chain
      functionality) important amino acid residues, which are necessary for DNA
      hydrolysis and binding of Mg(2+) and Ca(2+) ions. The affinity of DNA for this
      first example of a MLCh (K(M) = 0.3 microM) was 150- to 200-fold higher than for
      human DNase I.

PMID- 24919597
TI  - Predictors of 30-day hospital readmission following ischemic and hemorrhagic
      stroke.
AB  - Stroke patients have a high rate of 30-day readmission. Understanding the
      characteristics of patients at high risk of readmission is critical. A
      retrospective case-control study was designed to determine factors associated
      with 30-day readmission after stroke. A total of 79 cases with acute ischemic or
      hemorrhagic strokes readmitted to the same hospital within 30 days were compared
      with 86 frequency-matched controls. Readmitted patients were more likely to have
      had >=2 hospitalizations in the year prior to stroke (21.5% vs 2.3% in controls,
      P < .001), and in the multivariate model, admission National Institutes of Health
      Stroke Score (NIHSS; odds ratio [OR] = 1.072; 95% confidence interval [CI] =
      1.021-1.126 per 1 point increase; P = .005), prior hospitalizations (OR = 2.205;
      95% CI = 1.426-3.412 per admission; P < .001), and absence of hyperlipidemia (OR
      = 0.444; 95% CI = 0.221-0.894; P = .023) were independently associated with
      readmission. The research team concludes that admission NIHSS and frequent prior
      hospitalizations are associated with 30-day readmission after stroke. If
      validated, these characteristics identify high-risk patients and focus efforts to
      reduce readmission. 

PMID- 24919598
TI  - Implementation of unit-based interventions to improve teamwork and patient safety
      on a medical service.
AB  - In a prior study involving 2 medical units, Structured Interdisciplinary Rounds
      (SIDRs) improved teamwork and reduced adverse events (AEs). SIDR was implemented
      on 5 additional units, and a pre- versus postintervention comparison was
      performed. SIDR combined a structured format for communication with daily
      interprofessional meetings. Teamwork was assessed using the Safety Attitudes
      Questionnaire (score range = 0-100), and AEs were identified using queries of
      information systems confirmed by 2 physician researchers. Paired analyses for 82
      professionals completing surveys both pre and post implementation revealed
      improved teamwork (mean 76.8 +/- 14.3 vs 80.5 +/- 11.6; P = .02), which was
      driven mainly by nurses (76.4 +/- 14.1 vs 80.8 +/- 10.4; P = .009). The AE rate
      was similar across study periods (3.90 vs 4.07 per 100 patient days; adjusted IRR
      = 1.08; P = .60). SIDR improved teamwork yet did not reduce AEs. Higher baseline
      teamwork scores and lower AE rates than the prior study may reflect a positive
      cultural shift that began prior to the current study. 

PMID- 24919599
TI  - Humoral immune response to Shiga Toxin 2 (Stx2) among Brazilian urban children
      with hemolytic uremic syndrome and healthy controls.
AB  - BACKGROUND: Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is
      associated with hemolytic uremic syndrome (HUS), the main cause of acute renal
      failure in early childhood. Stx is essential in the pathogenesis of HUS, which
      has been mostly related to Stx2-producing isolates. Very limited data exist on
      the immune response to STEC in the Brazilian population. In this study, the
      prevalence of immunoglobulin G (IgG) antibodies to Stx2 was investigated in sera
      of children diagnosed with HUS and of healthy children in the city of Sao Paulo,
      Brazil. METHODS: IgG-antibody reactivity to Stx2 was determined by immunoblotting
      (WB) and enzyme-linked immunosorbent assay (ELISA) in sera from 13 children with
      HUS aged 8 months to 6 years and 54 healthy urban children aged 5 months to 7
      years. RESULTS: A positive immune response to the A and B subunits of Stx2 was
      observed in 46.1% HUS patients and in 16.6% healthy individuals by WB. All HUS
      patients and 62.9% healthy children showed IgG antibodies to the Stx2 A subunit.
      The frequency of antibodies to both subunits or only to the A subunit of Stx2 was
      significantly higher in HUS patients than controls (p<0.05). Also, the mean OD
      value obtained by ELISA was higher in that group. Considering children's age, the
      frequency of reactivity to either the A subunit or both subunits of Stx2 was
      considerably higher in HUS children up to three years old compared to controls in
      the same age range. Moreover, in almost 37% of healthy children, no immune
      response to Stx2 was detected independently of the child's age. CONCLUSIONS: The
      seroepidemiolgy of anti-Stx2 antibodies was described for the first time in
      healthy children and children with HUS in Brazil. The percentage of individuals
      showing antibodies against Stx2 was higher among HUS patients than controls, and
      in spite of the low number of notified HUS cases, STEC strains are circulating in
      our settings. In addition, the results obtained also corroborated previous data
      on the increased sensitivity and specificity of WB compared to toxin-based enzyme
      immunoassays.

PMID- 24919600
TI  - Passionate scholarship or academic safety: an ethical issue.
AB  - Are we passionate scholars or is academic safety something to which we aspire? Do
      we teach our students one thing and practice another? Are some forms of
      scholarship more acclaimed than others, some methodologies more acceptable? What
      are the ethical implications in these various questions? In this article, I
      outline my experiences, both as a student researcher and as an educator, that
      have brought me to ask these things. Holism is an ideal that many nursing
      students are taught and encouraged to bring to their practice, and yet holism
      does not seem, in many instances, to be supported in academia or in bedside
      practice. I suggest the possible causes for these difficulties and propose
      solutions. I suggest that the bedrock of ethical practice, both in the academy
      and with patients, is to bring all of who we are, the alchemic mystery of holism,
      to everything we do. 

PMID- 24919601
TI  - Reply: To PMID 24708382.

PMID- 24919602
TI  - Optimization of medium composition for 3-hydroxycarboxylic acid production by
      Pseudomonas mendocina-biodegraded polyhydroxybutyrate.
AB  - We optimized the culture medium for 3-hydroxycarboxylic acid production by
      Pseudomonas mendocina DS-04-T-biodegraded polyhydroxybutyrate (PHB) using the
      Plackett-Burman design, steepest ascent method, and Box-Behnken design. The
      optimized concentrations of the constituents of the culture medium were as
      follows: PHB (7.57 g/L), NH4 Cl (5.0 g/L), KH2 PO4 (2.64 g/L), Na2 HPO4 .12H2 O
      (12 g/L), MgSO4 .7H2 O (0.5 g/L), and CaCl2 .2H2 O (5 mg/L). The yield of 3
      hydroxycarboxylic acid obtained using the optimized culture medium was 56.8 +/-
      1.64%, which was 2.5-fold higher than that obtained when the unoptimized culture
      medium was used.

PMID- 24919603
TI  - Greater fear of hypoglycaemia with premixed insulin than with basal-bolus insulin
      glargine and glulisine: patient-reported outcomes from a 60-week randomised
      study.
AB  - AIM: To assess the effect of initiating insulin treatment on quality of life of
      patients with type 2 diabetes (T2DM) in the 60-week All-to-Target trial
      (NCT00384085). METHODS: Patient-reported outcomes from a phase IV, multicentre,
      randomised, open-label, parallel-group study were analysed. Participants were
      randomised to: insulin glargine with up to one insulin glulisine injection (G +
      1); insulin glargine with stepwise addition of up to three insulin glulisine
      injections (G + 3); or twice-daily premixed 70/30 insulin protamine-aspart/aspart
      (PM-2). Patient-reported outcome questionnaires were administered at weeks 0, 6,
      12, 24, 36, 48 and 60. RESULTS: There were no between-group differences in the
      Psychosocial Adjustment to Illness State-Self Report (PAIS-SR) or in the EuroQoL
      Group Five-Dimension Self-Report Index Questionnaire (EQ-5D) from baseline to
      week 60; however, PAIS-SR scores improved significantly over this period in the G
      + 3 group (p = 0.0016) and EQ-5D scores worsened significantly in the PM-2 group
      (p = 0.02). Hypoglycemia Fear Survey Behaviour and Worry subscales worsened
      significantly for all groups, with greater deterioration being observed in the PM
      2 group than in the G + 1 group (Behaviour, p = 0.0050; Worry, p = 0.0017) and G
      + 3 groups (Behaviour, p = 0.0105; Worry, p = 0.0016). Total scores on the
      Diabetes Quality of Life (DQoL) questionnaire improved more in the G + 3 group
      than in the PM-2 group over the study period (p = 0.0284), with all groups
      showing a significant improvement in DQoL score over time. CONCLUSION: Insulin
      glargine-based regimens showed advantages over premixed insulin in a number of
      patient-reported outcome measures. The potential impact on fear of hypoglycaemia
      may be of particular relevance when addressing the major barriers to early
      insulin treatment.

PMID- 24919604
TI  - The effects of a diet rich in inulin or wheat fibre on markers of cardiovascular
      disease in overweight male subjects.
AB  - BACKGROUND: Previous studies suggest that the beneficial health effects of a diet
      rich in whole grains could be a result of the individual fibres found in the
      grain. The present study aimed to investigate the influence of a diet high in
      either wheat fibre (as an example of an insoluble fibre) or inulin (a
      nondigestible carbohydrate) on markers of cardiovascular disease. METHODS: Ten
      male participants classified as at higher risk of cardiovascular disease [mean
      (SD) body mass index 30.2 (3) kg m(-2) , mean (SD) waist circumference 106.4 (7)
      cm, mean (SD) age 39.8 (9) years] were recruited to a randomised, controlled,
      cross-over study comparing the consumption of bespoke bread rolls containing
      either inulin, wheat germ or refined grain (control) (15 g day(-1) ) for 4 weeks
      with a 4-week washout period between each regime. At the end of each regime,
      participants underwent an oral glucose tolerance test (OGTT), measures of pulse
      wave velocity (PWV), 24-h ambulatory blood pressure (AMBP), plasma lipid status
      and markers of glucose control. RESULTS: There was no difference in measures of
      glucose control, lipid status, 24-h AMBP or PWV after the intervention periods
      and no changes compared to baseline. There was no significant difference between
      OGTT glucose and insulin time profiles; however, there was a significant
      difference in area under the curves between the wheat fibre and control
      interventions when comparing change from baseline (control +10.2%, inulin +4.3%,
      wheat fibre -2.5%; P = 0.03). CONCLUSIONS: Only limited differences between the
      interventions were identified, perhaps as a consequence of the amount of fibre
      used and intervention length. The wheat germ intervention resulted in a
      significant reduction in glucose area under the curve, suggesting that this fibre
      may aid glucose control.

PMID- 24919605
TI  - Liver transplantation versus liver resection for hepatocellular carcinoma: a meta
      analysis.
AB  - BACKGROUND: Liver transplantation (LT) and liver resection (LR) are currently
      considered the standard treatment of patients with hepatocellular carcinoma
      (HCC). However, the outcomes of LT and LR are still inconclusive. DATA SOURCES:
      MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies.
      Surgical safety indices such as treatment-related morbidity and mortality, and
      efficacy indices such as overall and tumor-free survival outcomes were evaluated.
      Weighted mean differences and odds ratios (ORs) were calculated using a random
      effects model. RESULTS: Seventeen studies were included in this meta-analysis. LT
      achieved significantly higher rates of surgery-related morbidity (OR=1.47; 95%
      CI: 1.02-2.13) and mortality (OR=2.12; 95% CI: 1.11-4.05). Likewise, the 1-year
      survival rate was lower in LT (OR=0.86; 95% CI: 0.61-1.20). However, the 3- and 5
      year survival rates were significantly higher in LT than in LR and the ORs were
      1.12 (95% CI: 0.96-1.30) in 3 years and 1.84 (95% CI: 1.49-2.28) in 5 years.
      Furthermore, the tumor-free survival rate in LT was significantly higher than
      that in LR in 1, 3, 5 years after surgery, with the ORs of 1.72 (95% CI: 1.24
      2.41), 3.75 (95% CI: 2.94-4.78) and 5.64 (95% CI: 4.35-7.31), respectively.
      CONCLUSIONS: One-year morbidity and mortality are higher in LT than in LR for
      patients with HCC. However, long-term survival and tumor-free survival rates are
      higher in patients treated with LT than those treated with LR.

PMID- 24919606
TI  - Different cava reconstruction techniques in liver transplantation: piggyback
      versus cava resection.
AB  - BACKGROUND: Originally, cava reconstruction (CR) in liver transplantation meant
      complete resection and reinsertion of the donor cava. Alternatively, preservation
      of the recipients inferior vena cava (IVC) with side-to-side anastomosis (known
      as "piggyback") can be performed. Here, partial clamping maintains blood flow of
      the IVC, which may improve cardiovascular stability, reduce blood loss and
      stabilize kidney function. The aim of this study was to compare both techniques
      with particular focus on kidney function. METHODS: A series of 414 patients who
      had had adult liver transplantations (2006-2009) were included. Among them, 176
      (42.5%) patients had piggyback and 238 had classical CR operation, 112 (27.1%) of
      the patients underwent CR accompanied with veno-venous bypass (CR-B) and 126
      (30.4%) without a bypass. The choice of either technique was based on the
      surgeons' individual preference. Kidney function [serum creatinine, calculated
      glomerular filtration rate (GFR), RIFLE stages] was assessed over 14 days.
      RESULTS: Lab-MELD scores were significantly higher in CR-B (22.5+/-11.0) than in
      CR (17.3+/-9.0) and piggyback (18.8+/-10.0) (P=0.008). Unexpectedly, the
      incidences of arterial stenoses (P=0.045) and biliary leaks (P=0.042) were
      significantly increased in piggyback. Preoperative serum creatinine levels were
      the highest in CR-B [1.45+/-1.17 vs 1.25+/-0.85 (piggyback) and 1.13+/-0.60 mg/dL
      (CR); P=0.033]. Although a worsening of postoperative kidney function was
      observed among all groups, this was most pronounced in CR-B [creatinine day 14:
      1.67+/-1.40 vs 1.35+/-0.96 (piggyback) and 1.45+/-1.03 mg/dL (CR); P=0.102].
      Accordingly, the proportion of patients displaying RIFLE stages >=2 was the
      highest in CR/CR-B (26%/19%) when compared to piggyback (18%). CONCLUSIONS:
      Piggyback revealed a shorter warm ischemic time, a reduced blood loss, and a
      decreased risk of acute kidney failure. Thus, piggyback is a useful technique,
      which should be applied in standard procedures. When piggyback is unfeasible,
      cava replacement, which displayed a lower incidence of vascular and biliary
      complications in our study, remains as a safe alternative.

PMID- 24919607
TI  - Pretransplant absolute monocyte count in peripheral blood predicts posttransplant
      tumor prognosis in patients undergoing liver transplantation for hepatocellular
      carcinoma.
AB  - BACKGROUND: Preoperative absolute monocyte count in peripheral blood (AMCPB) is
      closely associated with prognoses in not only various malignancies but also
      hepatocellular carcinoma (HCC). The purpose of this study was to evaluate whether
      pretransplant AMCPB predicts posttransplant outcomes in patients with HCC
      undergoing liver transplantation (LT). METHOD: We retrospectively analyzed
      relationships between clinicopathologic factors involving pretransplant AMCPB and
      tumor recurrence or survival in 256 patients who had undergone LT for HCC between
      January 2005 and April 2012. RESULTS: ROC curve analysis showed that AMCPB
      >200/mm(3) was a risk factor for tumor recurrence; 43 patients showed higher
      AMCPB (>200/mm(3)), whereas 213 showed lower AMCPB (<=200/mm(3)) at the time of
      LT. On multivariate analysis, pretransplant high AMCPB, positive findings in
      pretransplant (18)F-FDG PET/CT, pathological maximal tumor size >5 cm,
      intrahepatic metastasis, moderately or poorly differentiated tumor and
      microvascular invasion were independent factors affecting recurrence-free
      survival. When we performed subgroup analysis based on the Milan criteria, high
      AMCPB was an independent factor for predicting HCC recurrence in patients with
      tumor beyond the Milan criteria (P=0.004), and not for patients within the
      criteria. CONCLUSION: This study demonstrated that pretransplant AMCPB could
      predict tumor recurrence after LT for HCC, especially in patients with tumor
      beyond the Milan criteria.

PMID- 24919608
TI  - Impact of intra-operative cholangiography and parenchymal resection to donor
      liver function in living donor liver transplantation.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) has been widely accepted
      over the past decade, and hepatic dysfunction often occurs in the donor in the
      early stage after liver donation. The present study aimed to evaluate the effect
      of intra-operative cholangiography (IOC) and parenchymal resection on liver
      function of donors in LDLT, and to assess the role of IOC in influencing the
      biliary complications and improving the overall outcome. METHODS: Data from 40
      patients who had donated their right lobes for LDLT were analyzed. Total
      bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) at different
      time points were compared, and the follow-up data and the biliary complications
      were also analyzed. RESULTS: The ALT and AST values were significantly increased
      after IOC (P<0.001) and parenchymal resection (P<0.001). However, the median
      values of TB, ALP and GGT were not significantly influenced by IOC (P>0.05) or
      parenchymal resection (P>0.05). The biochemical changes caused by IOC or
      parenchymal resection were not correlated with the degree of post-operative liver
      injury or the recovery of liver function. The liver functions of the donors after
      operation were stable, and none of the donors suffered from biliary stenosis or
      leakage during the follow-up. CONCLUSIONS: IOC and parenchymal resection may
      induce a transient increase in liver enzymes of donors in LDLT, but do not affect
      the recovery of liver function after operation. Moreover, the routine IOC is
      helpful to clarify the division line of the hepatic duct, thus reducing the
      biliary complication rate.

PMID- 24919609
TI  - Mesohepatectomy versus extended hemihepatectomy for centrally located
      hepatocellular carcinoma.
AB  - BACKGROUND: Extended hemihepatectomy is usually recommended to treat large
      centrally located hepatocellular carcinoma (HCC). However, the morbidity and
      mortality are high because of the postoperative liver failure. Mesohepatectomy is
      seldom used because of its technical complexity. This study aimed to evaluate the
      short-term and long-term curative effect of mesohepatectomy. METHODS: From
      January 2002 to September 2008, a total of 198 consecutive patients with
      centrally located HCC underwent hepatectomy in our department. According to the
      surgical procedures, they were divided into mesohepatectomy (group M, n=118),
      extended right hemihepatectomy (group RE, n=47) and extended left hemihepatectomy
      (group LE, n=33) groups. The surgical techniques, clinical pathological
      characteristics and outcomes were compared between group M, group RE and group
      LE. RESULTS: The operative time of group M was significantly longer than that of
      the other two groups (P<0.05); however the total bilirubin on postoperative day 3
      in group M was the lowest among the three groups (P<0.01). In group M, the number
      of the patients whose resection margin achieving 1 cm was significantly lower
      than that of the other two groups (P<0.05). The mortality rates in groups M, RE
      and LE were 2.5%, 8.5% and 3.0%, respectively (P>0.05). The morbidity rate in
      group M was significantly lower than that in group RE (37.3% vs 55.3%, P=0.034),
      but not in group LE (37.3% vs 24.2%, P=0.163). The biliary leakage tended to be
      more common in group M (10.2%, P>0.05). The incidence of postoperative liver
      failure in group M was significantly lower than that in group RE (1.7% vs 10.6%,
      P=0.032), but not in group LE (1.7% vs 6.1%, P=0.208). The 1-, 3- and 5-year
      tumor-free survival rates and the overall survival rates after mesohepatectomy
      were 53.4%, 30.5% and 16.9% and 67.8%, 45.5% and 28.9%, respectively.
      CONCLUSIONS: Mesohepatectomy is a safe and effective technique for centrally
      located HCC patients. Compared with extended right hemihepatectomy,
      mesohepatectomy can retain residual liver volume to the maximum limit and reduce
      postoperative liver failure rate. But no significant advantage was found compared
      mesohepatectomy to extended left hemihepatectomy.

PMID- 24919610
TI  - Indocyanine green clearance test combined with MELD score in predicting the short
      term prognosis of patients with acute liver failure.
AB  - BACKGROUND: Acute liver failure (ALF) is an acute severe deterioration of liver
      function with high mortality. Early and accurate prognostic assessment of
      patients with ALF is critically important. Although the model for end-stage liver
      disease (MELD) scores and King's College Hospital (KCH) criteria are well
      accepted as predictive tools, their accuracy is unsatisfactory. The indocyanine
      green (ICG) clearance test (ICGR15, ICG retention rate at the 15 minutes) is a
      sensitive indicator of liver function. In this study, we investigated the
      efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We
      compared the predictive value of ICGR15 with the MELD scores and KCH criteria.
      METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited
      retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and
      relevant clinical and laboratory indices were analyzed within 24 hours of
      diagnosis. In addition, the MELD scores and KCH criteria were calculated.
      RESULTS: The three-month mortality of all patients was 47.83%. Age, serum total
      bilirubin and creatinine concentrations, international normalized ratio for
      prothrombin time, ICGR15, MELD scores and KCH criteria differed significantly
      between surviving and deceased patients. A positive correlation was observed
      between ICGR15 and MELD scores (r=0.328, P=0.006). The ICGR15-MELD model,
      Logit(P)=0.096XICGR15+0.174XMELD score-9.346, was constructed by logistic
      regression analysis. The area under the receiver operating characteristic curve
      was 0.855. When set the cut-off point to -0.4684, the sensitivity was 87.90% and
      specificity, 72.20%. The area under the receiver operating characteristic curve
      of the ICGR15-MELD model (0.855) was significantly higher than that of the ICGR15
      (0.793), MELD scores (0.776) and KCH criteria (0.659). Based on this cut-off
      value, the patients were divided into two groups. The mortality was 74.36% in the
      first group (ICGR15-MELD>=-0.4686) and 13.33% in the second group (ICGR15-MELD<
      0.4686), with a significant difference between the two groups (X(2)=25.307,
      P=0.000). CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD
      scores, and KCH criteria in predicting the short-term prognosis of patients with
      ALF.

PMID- 24919611
TI  - Acute liver failure in Chinese children: a multicenter investigation.
AB  - BACKGROUND: Currently, no documentation is available regarding Chinese children
      with acute liver failure (ALF). This study was undertaken to investigate
      etiologies and outcomes of Chinese children with ALF. METHODS: We retrospectively
      enrolled 32 pediatric patients with ALF admitted in five hospitals in different
      areas of China from January 2007 to December 2012. The coagulation indices, serum
      creatinine, serum lactate dehydrogenase, blood ammonia and prothrombin activity
      were analyzed; the relationship between these indices and mortality was evaluated
      by multivariate analysis. RESULTS: The most common causes of Chinese children
      with ALF were indeterminate etiology (15/32), drug toxicity (8/32), and acute
      cytomegalovirus hepatitis (6/32). Only 1 patient (3.13%) received liver
      transplantation and the spontaneous mortality of Chinese children with ALF was
      58.06% (18/31). Patients who eventually died had higher baseline levels of
      international normalized ratio (P=0.01), serum creatinine (P=0.04), serum lactate
      dehydrogenase (P=0.01), blood ammonia (P<0.01) and lower prothrombin activity
      (P=0.01) than those who survived. Multivariate analysis showed that the entry
      blood ammonia was the only independent factor significantly associated with
      mortality (odds ratio=1.069, 95% confidence interval 1.023-1.117, P<0.01) and it
      had a sensitivity of 94.74%, a specificity of 84.62% and an accuracy of 90.63%
      for predicting the death. Based on the established model, with an increase of
      blood ammonia level, the risk of mortality would increase by 6.9%. CONCLUSIONS:
      The indeterminate causes predominated in the etiologies of ALF in Chinese
      children. The spontaneous mortality of pediatric patients with ALF was high,
      whereas the proportion of patients undergoing liver transplantation was
      significantly low. Entry blood ammonia was a reliable predictor for the death of
      pediatric patients with ALF.

PMID- 24919613
TI  - HepG2 cells recovered from apoptosis show altered drug responses and
      invasiveness.
AB  - BACKGROUND: Cancer relapse, associated with increased drug resistance and rate of
      metastasis, often follows completion of chemotherapy but the cancer escape
      mechanisms are still incompletely understood. Percutaneous ethanol injection
      (PEI) has been used for treating hepatocellular carcinoma (HCC) for decades,
      while the recurrence after PEI treatment remains a major limitation. Recent
      evidence mounted that cancer cells could survive from chemical induced apoptosis,
      suggesting a potential route through which cancer relapse may occur. This study
      focuses on the consequence of HepG2 recovery from ethanol-induced apoptotic
      event. METHODS: The model of HepG2 recovery from ethanol-induced apoptotic event
      was established by live cell imaging, BrdU assay and Western blotting. MTT assay,
      wound healing assay and invasion assay were used to investigate the behavior of
      HepG2 after recovery. RESULTS: HepG2 cells could recover from ethanol-induced
      apoptosis. These cells changed their behaviors such as drug resistance, mobility
      and invasiveness. On average, the recovered HepG2 cell clones were found to be
      46% more resistant to ethanol and 84% higher in mobility. The recovered clones
      became 58.2% more sensitive to 5-fluorouracil. CONCLUSIONS: HepG2 cells can
      recover from ethanol-induced apoptotic event. These cells became more resistant
      to ethanol and more invasive. Although the recovered cell clones were more
      resistant to ethanol, they became more sensitive to 5-fluorouracil treatment.

PMID- 24919612
TI  - Ron receptor-dependent gene regulation of Kupffer cells during endotoxemia.
AB  - BACKGROUND: Ron receptor tyrosine kinase signaling in macrophages, including
      Kupffer cells and alveolar macrophages, suppresses endotoxin-induced
      proinflammatory cytokine/chemokine production. Further, we have also identified
      genes from Ron replete and Ron deplete livers that were differentially expressed
      during the progression of liver inflammation associated with acute liver failure
      in mice by microarray analyses. While important genes and signaling pathways have
      been identified downstream of Ron signaling during progression of inflammation by
      this approach, the precise role that Ron receptor plays in regulating the
      transcriptional landscape in macrophages, and particular in isolated Kupffer
      cells, has still not been investigated. METHODS: Kupffer cells were isolated from
      wild-type (TK+/+) and Ron tyrosine kinase deficient (TK-/-) mice. Ex vivo, the
      cells were treated with lipopolysaccharide (LPS) in the presence or absence of
      the Ron ligand, hepatocyte growth factor-like protein (HGFL). Microarray and qRT
      PCR analyses were utilized to identify alterations in gene expression between
      genotypes. RESULTS: Microarray analyses identified genes expressed differentially
      in TK+/+ and TK-/- Kupffer cells basally as well as after HGFL and LPS treatment.
      Interestingly, our studies identified Mefv, a gene that codes for the anti
      inflammatory protein pyrin, as an HGFL-stimulated Ron-dependent gene. Moreover,
      lipocalin 2, a proinflammatory gene, which is induced by LPS, was significantly
      suppressed by HGFL treatment. Microarray results were validated by qRT-PCR
      studies on Kupffer cells treated with LPS and HGFL. CONCLUSION: The studies
      herein suggest a novel mechanism whereby HGFL-induced Ron receptor activation
      promotes the expression of anti-inflammatory genes while inhibiting genes
      involved in inflammation with a net effect of diminished inflammation in
      macrophages.

PMID- 24919614
TI  - Detection of liver micrometastases from colorectal origin by perfusion CT in a
      rat model.
AB  - BACKGROUND: Some patients with colorectal carcinoma have liver metastases (LMs)
      which cannot be detected by conventional imaging. This study aimed to assess
      whether hepatic perfusion changes induced by micrometastases can be detected by
      perfusion computed tomography (CT). METHODS: LMs were produced in rats by
      injecting carcinoma cells into the portal vein. Perfusion CT was performed at
      microscopic (day 10), interval (day 17), and macroscopic stage (day 34).
      Perfusion parameters were computed using a dual-input one-compartmental model.
      RESULTS: Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm,
      respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic
      stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41%
      (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240%
      (P=0.001) in portal delay, respectively. CONCLUSIONS: LMs with a mean diameter
      between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by
      CT. Such detection may help to select patients and propose chemotherapy at the
      time of primary tumor resection.

PMID- 24919615
TI  - Sodium butyrate protects against toxin-induced acute liver failure in rats.
AB  - BACKGROUND: Acute liver failure (ALF) is a serious clinical syndrome with high
      mortality. Sodium butyrate has been shown to alleviate organ injury in a wide
      variety of preclinical models of critical diseases. The aim of this study was to
      investigate the protective effect of sodium butyrate on ALF in rats. METHODS: All
      rats were randomly divided into control, model and sodium butyrate treatment
      groups. Except the control group, the rats were induced ALF animal model by
      subcutaneous injection of human serum albumin+ D
      galactosamine+lipopolysaccharide. After induction of ALF, the rats in the
      treatment group received sodium butyrate (500 mg/kg) at 12-hour or 24-hour time
      point. Fourty-eight hours after ALF induction, the animals were sacrificed and
      samples were harvested. Serum endotoxin, high mobility group box-1 (HMGB1), liver
      function parameters, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma
      (IFN-gamma) were measured. The expression of HMGB1 and nuclear factor-kappa B (NF
      kappaB) p65 protein in liver tissue was detected by Western blotting. The
      histological changes of liver and intestine were examined. The survival duration
      was also observed. RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1, TNF
      alpha and IFN-gamma were significantly increased and the liver histology showed
      more severe histopathological injury in the model group compared with the control
      group (P<0.05). Compared to the model group, sodium butyrate treatment
      significantly improved the histopathological changes in the liver and intestine,
      reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF
      kappaB p65 proteins in liver tissue, and prolonged the survival duration
      regardless of treatment at 12 hours or 24 hours after induction of ALF (P<0.05).
      CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats.
      The mechanisms may be due to direct hepatoprotection and decreased intestinal
      permeability.

PMID- 24919616
TI  - Emergency cholecystectomy vs percutaneous cholecystostomy plus delayed
      cholecystectomy for patients with acute cholecystitis.
AB  - BACKGROUND: In low-risk patients with acute cholecystitis who did not respond to
      nonoperative treatment, we prospectively compared treatment with emergency
      laparoscopic cholecystectomy or percutaneous transhepatic cholecystostomy
      followed by delayed cholecystectomy. METHODS: In 91 patients (American Society of
      Anesthesiologists class I or II) who had symptoms of acute cholecystitis >=72
      hours at hospital admission and who did not respond to nonoperative treatment (48
      hours), 48 patients were treated with emergency laparoscopic cholecystectomy and
      43 patients were treated with delayed cholecystectomy at >=4 weeks after
      insertion of a percutaneous transhepatic cholecystostomy catheter. After initial
      treatment, the patients were followed up for 23 months on average (range 7-29).
      RESULT: Compared with the patients who had emergency laparoscopic
      cholecystectomy, the patients who were treated with percutaneous transhepatic
      cholecystostomy and delayed cholecystectomy had a lower frequency of conversion
      to open surgery [19 (40%) vs 8 (19%); P=0.029], a frequency of intraoperative
      bleeding >=100 mL [16 (33%) vs 4 (9%); P=0.006], a mean postoperative hospital
      stay (5.3+/-3.3 vs 3.0+/-2.4 days; P=0.001), and a frequency of complications [17
      (35%) vs 4 (9%); P=0.003]. CONCLUSION: In patients with acute cholecystitis who
      presented to the hospital >=72 hours after symptom onset and did not respond to
      nonoperative treatment for 48 hours, percutaneous transhepatic cholecystostomy
      with delayed laparoscopic cholecystectomy produced better outcomes and fewer
      complications than emergency laparoscopic cholecystectomy.

PMID- 24919617
TI  - Validation of the moderate severity category of acute pancreatitis defined by
      determinant-based classification.
AB  - BACKGROUND: Recent international multidisciplinary consultation proposed the use
      of local (sterile or infected pancreatic necrosis) and/or systemic determinants
      (organ failure) in the stratification of acute pancreatitis. The present study
      was to validate the moderate severity category by international multidisciplinary
      consultation definitions. METHODS: Ninety-two consecutive patients with severe
      acute pancreatitis (according to the 1992 Atlanta classification) were classified
      into (i) moderate acute pancreatitis group with the presence of sterile (peri-)
      pancreatic necrosis and/or transient organ failure; and (ii) severe/critical
      acute pancreatitis group with the presence of sterile or infected pancreatic
      necrosis and/or persistent organ failure. Demographic and clinical outcomes were
      compared between the two groups. RESULTS: Compared with the severe/critical group
      (n=59), the moderate group (n=33) had lower clinical and computerized tomographic
      scores (both P<0.05). They also had a lower incidence of pancreatic necrosis
      (45.5% vs 71.2%, P=0.015), infection (9.1% vs 37.3%, P=0.004), ICU admission (0%
      vs 27.1%, P=0.001), and shorter hospital stay (15+/-5 vs 27+/-12 days; P<0.001).
      A subgroup analysis showed that the moderate group also had significantly lower
      ICU admission rates, shorter hospital stay and lower rate of infection compared
      with the severe group (n=51). No patients died in the moderate group but 7
      patients died in the severe/critical group (4 for severe group). CONCLUSIONS: Our
      data suggest that the definition of moderate acute pancreatitis, as suggested by
      the international multidisciplinary consultation as sterile (peri-) pancreatic
      necrosis and/or transient organ failure, is an accurate category of acute
      pancreatitis.

PMID- 24919618
TI  - Possible benefit of splenectomy in liver transplantation for autoimmune
      hepatitis.
AB  - Liver transplantation for autoimmune hepatitis (AIH) is usually successful with
      excellent long-term outcomes, but primary disease may recur. The recurrence of
      AIH is a significant cause of graft loss. This study was to analyze the effect of
      splenectomy in preventing AIH relapse. The clinical courses of 12 patients who
      had transplantation for AIH were analyzed retrospectively. All patients were
      subjected to transplantation for end-stage liver disease caused by chronic AIH.
      Based on the duration of immunosuppressive treatment before liver
      transplantation, simultaneous splenectomy was performed in ten patients. Two
      patients underwent liver transplantation without splenectomy, one of them
      developed recurrent AIH and died from graft failure caused by AIH relapse.
      However, no episode of AIH recurrence was observed in patients who had undergone
      simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse
      in some patients with high risk factors. 

PMID- 24919619
TI  - Comment on "Terry's nail: an overlooked physical finding in cirrhosis".

PMID- 24919620
TI  - The author reply.

PMID- 24919621
TI  - Hand usage pattern and upper body discomfort of desktop touchscreen users.
AB  - A laboratory study was conducted to determine how users of different handedness
      interact with desktop touchscreen displays and how the hand usage pattern
      influences their body discomfort development. Twenty-one participants in three
      different handedness groups conducted simple web-browsing for 30 minutes using a
      23" touchscreen display while their subjective body discomfort, frequency of use
      of each hand and touch area preference were periodically quantified. Participants
      reported a gradual increase in body discomfort during web-browsing, and the
      increments in body discomfort varied between handedness groups for some body
      parts. Results also show that right-handed participants had stronger laterality
      than the left-handed, and ambidextrous participants used both hands more evenly
      than other participants, suggesting associations between the hand usage pattern
      and body discomfort development. Findings of the current study suggest that body
      discomfort of desktop touchscreen display users could be moderated by user
      interface improvements and user training. PRACTITIONER SUMMARY: Body discomfort
      development of desktop touchscreen users may be influenced by their hand usage
      pattern. Findings of this laboratory study suggest that user discomfort may be
      moderated by placing menu items in the lower area within the display or training
      users to alternate hands when conducting touch gestures.

PMID- 24919623
TI  - Successful treatment of subungual fibromas of tuberous sclerosis with topical
      rapamycin.

PMID- 24919622
TI  - Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in
      diabetic rats: a role for neuronal ROCK.
AB  - INTRODUCTION: The pathogenesis of diabetic erectile dysfunction (ED) includes
      neuropathy, but the molecular basis for neurogenic ED is incompletely understood.
      The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but
      its role in diabetic neurogenic ED is not known. AIMS: The aim of this study was
      to determine whether hydroxyl fasudil, a ROCK inhibitor, affects diabetic
      neuropathy-related ED. METHODS: Type 1 diabetes mellitus was induced in male rats
      by streptozotocin (75 mg/kg, intraperitoneally). After 8 weeks, diabetic rats
      were administered hydroxyl fasudil, a selective ROCK inhibitor (10 mg/kg/day,
      intraperitoneally) or vehicle, for 4 weeks. Age-matched control, nondiabetic,
      rats were treated intraperitoneally for 4 weeks with saline. At week 12, after a
      2 day washout, neuro-stimulated erectile function was evaluated. Major pelvic
      ganglia (MPG) were collected for Western blot analysis of RhoA, ROCK-1, ROCK-2,
      phospho (P)-AKT (Ser(473) ), and P-phosphatase and tensin homolog (P-PTEN)
      (Ser(380) /Thr(382/383) ). MAIN OUTCOME MEASURES: Effect of ROCK inhibitor
      hydroxyl fasudil on erectile function and ROCK/P-AKT/P-PTEN pathway in the MPG of
      diabetic rats. RESULTS: Erectile response was significantly (P < 0.05) reduced in
      diabetic rats compared with nondiabetic rats and was preserved (P < 0.05) in
      diabetic rats treated with hydroxyl fasudil. In diabetic rats, RhoA and ROCK-2
      protein expressions in MPG were increased (P < 0.05) and remained increased in
      hydroxyl fasudil-treated rats. P-AKT (Ser(473) ) expression was decreased (P <
      0.05), whereas P-PTEN (Ser(380) /Thr(382/383) ) expression was increased (P <
      0.05) in MPG of diabetic rats compared with nondiabetic rats, and both were
      reversed (P < 0.05) in diabetic rats treated with hydroxyl fasudil. CONCLUSION:
      Improved erectile function and restored P-AKT and P-PTEN in the MPG with hydroxyl
      fasudil treatment suggest the role of Rho signaling via PTEN/AKT pathway in
      neurogenic diabetic ED.

PMID- 24919624
TI  - The journal has always been concerned to develop its engagement with its
      readership. Introduction.

PMID- 24919625
TI  - Introduction to three clinical papers.

PMID- 24919626
TI  - On the capacity to suffer one's self.
AB  - Problems in the establishment of the sense of a 'psychic' skin, in the ways
      described by Bick and Meltzer for example, commonly give rise to distortions in
      the capacity for self-experiences as a consequence of difficulties in relation to
      projective and identificatory processes. These latter may acquire a markedly
      adhesive character as a defence against the anxieties that arise. This makes for
      considerable technical difficulties in an analysis. This essay addresses the
      nature of these problems and considers some of the ways in which they may be
      approached clinically. 

PMID- 24919627
TI  - On the analysand's need to know the real person of the analyst.
AB  - But the conscious achievement of inner unity clings to human relationships as to
      an indispensable condition. C.G.Jung (1946, p.233) Based on personal experience
      the main part of this paper explores the theme of the analysand's need to know
      the real person of the analyst and the importance, on occasion, of the analyst's
      disclosure of subjectivity. The concluding part offers suggestions about working
      with analysands where there is early emotional damage and deficits in
      relationship. 

PMID- 24919628
TI  - Converting a Freudian analysis into a Jungian one: obsession, addiction, and an
      answer from Job.
AB  - In his analyses of obsessional patients, Sigmund Freud suggested that they
      suffered from intrusive cognitions and compulsive activities. Early
      psychoanalysts delineated the phenomenology of obsessionality, but did not
      differentiate what is currently termed obsessive-compulsive disorder from
      obsessional personality. However, it was widely recognized that the success of
      psychoanalysis with obsessional patients was limited due to rigid
      characterological defences and transference resistances. The present paper
      examines the case of a middle-aged obsessional academic who had been treated for
      nearly twenty years in a 'classical' Freudian psychoanalysis prior to entering
      Jungian analysis. It examines how persistent focus on Oedipal conflicts
      undesirably reinforced the transference resistance in this obsessional man, and
      suggests that focusing instead on diminishing the harshness of the super-ego via
      the therapeutic alliance, and fostering faith in the salutary aspects of
      unconscious processing has led to salutary results in this case. The biblical
      book of Job is adopted as ancient instruction in how to address the scrupulosity
      and addictive mental structuring of obsessionality in analysis. 

PMID- 24919629
TI  - Synchronicity, the infinite unrepressed, dissociation and the interpersonal.
AB  - This paper uses the logic derived by Matte Blanco to provide an Archimedean point
      and a mathematics, both of which Jung complained of lacking, with which to
      validate the notion of synchronicity and to demonstrate that it is one of the
      inevitable properties of an unconscious which is unrepressed such as Jung's
      collective unconscious, and that such an unconscious will also be affective and
      interpersonal as well as intrapersonal. These have important clinical
      implications. After an exposition of Matte Blanco's thinking, some clinical
      material is presented of an episode in which patient and author both suffered the
      same psychosomatic symptom some time just prior to a session. Correspondences
      between Matte Blanco's logically derived ideas and Jung's phenomenological
      observations are made. 

PMID- 24919630
TI  - Levels of unconsciousness and their formal structure.
AB  - This brief essay replies to Carvalho's exposition of a formal approach to the
      concept of the unconscious which is originally due to Ignacio Matte Blanco (1908
      1995), a psychoanalyst from Chile. It's a challenge - first because I have been
      largely unfamiliar with the details of Matte Blanco's approach, and second
      because the space available for this reply does not allow me to be as precise as
      Carvalho's essay no doubt deserves. I will start with some remarks about how I
      see Matte Blanco's system from a mathematical perspective and then try to relate
      it to some of the core features of Pauli's and Jung's thinking. I will conclude
      with a tentative proposal of how Matte Blanco's strata between full consciousness
      and most undifferentiated unconscious can be related to the tension between ontic
      and epistemic accounts. 

PMID- 24919631
TI  - Learning from the patient: the East, synchronicity and transference in the
      history of an unknown case of C.G. Jung.
AB  - This article presents the history of one until now unknown case of C.G. Jung:
      Maggy Reichstein. Born in Indonesia in 1894 in a very aristocratic family, she
      brought her sister to Zurich to be treated by Jung in 1919, and later she herself
      was in analysis with him. Jung used her case as example in his lecture in 1937 on
      the realities of practical psychotherapy, relating it to the process of
      transference and countertransference. Jung deepened his studies in Eastern
      psychology after a series of dreams she had, which culminated in the Yoga
      Kundalini Seminars. She was also the case presented in his article of 1951 on the
      concept of synchronicity. Jung wrote that her case, concerning synchronicity,
      remained unique in his experience. Jung also published some of her mandalas. He
      considered her able to understand his ideas in depth. Reichstein was for Jung an
      important case, which challenged and triggered his interests in different
      subjects. 

PMID- 24919632
TI  - Causality as individual essence: its bearing on synchronicity.
AB  - Causality, time, and number are subjectively lived realities and need to be
      noticed as such. Fundamental to the wide range of living experience, they are
      also basic to scientific knowing. In this article I examine causality in relation
      to an article on synchronicity by Harald Atmanspacher and Wolfgang Fach. My
      examination is neither scientific nor metaphysical, but rather phenomenological,
      as it is a clarification of form as individual essence of a thing. This non
      material form of an individual thing in the widest sense of the word 'thing' was
      rejected and so lost during modern seventeenth-century science but, renewed now,
      can help describe synchronicity. A commentary by William Willeford follows. 

PMID- 24919633
TI  - A commentary on 'causality as individual essence: its bearing on synchronicity'.

PMID- 24919634
TI  - Roles of causation and meaning for interpreting correlations.
AB  - The essays by Tougas and Willeford address, among other things, a number of ways
      to understand causation, which play crucial roles in the framework of thinking
      proposed by Pauli and Jung. The intention of my following reply is to say a few
      words about how these options are related to one another within our
      reconstruction of the Pauli-Jung conjecture. In the tradition of the sciences,
      looking for causation has become a virtually innate reflex to interpret
      empirically observed correlations. The concept of synchronicity suggests looking
      for meaningful coincidences as an alternative, complementary interpretation,
      particularly appropriate for psychophysical correlations. 

PMID- 24919638
TI  - Association between childhood adversities and long-term suicidality among South
      Africans from the results of the South African Stress and Health study: a cross
      sectional study.
AB  - OBJECTIVE: Suicide and suicidal behaviours are significant public health problems
      and a leading cause of death worldwide and in South Africa. We examined the
      association between childhood adversities and suicidal behaviour over the life
      course. METHODS: A national probability sample of 4351 South African adult
      participants (aged 18 years and older) in the South African Stress and Health
      (SASH) study was interviewed as part of the World Mental Health Surveys
      initiative. Respondents provided sociodemographic and diagnostic information, as
      well as an account of suicide-related thoughts and behaviours. Suicidality or
      suicidal behaviour were defined as were defined as suicide attempts and suicidal
      ideation in the total sample, and suicide plans and attempts among ideators.
      Childhood adversities included physical abuse, sexual abuse, parental death,
      parental divorce, other parental loss, family violence, physical illness and
      financial adversity. The association between suicidality and childhood
      adversities was examined using discrete-time survival models. RESULTS: More than
      a third of the respondents with suicidal behaviour experienced at least one
      childhood adversity, with physical abuse, parental death and parental divorce
      being the most prevalent adversities. Physical abuse, sexual abuse and parental
      divorce were identified as significant risk markers for lifetime suicide
      attempts, while physical abuse and parental divorce were significantly correlated
      with suicidal ideation. Two or more childhood adversities were associated with a
      twofold higher risk of lifetime suicide attempts. Sexual abuse (OR 9.3), parental
      divorce (OR 3.1) and childhood physical abuse (OR 2.2) had the strongest
      associations with lifetime suicide attempts. The effect of childhood adversities
      on suicidal tendencies varied over the life course. For example, sexual abuse was
      significantly associated with suicide attempts during childhood and teen years,
      but not during young and later adulthood. CONCLUSIONS: Childhood adversities,
      especially sexual abuse, physical abuse and parental divorce, are important risk
      factors for the onset and persistence of suicidal behaviour, with this risk being
      greatest in childhood and adolescence.

PMID- 24919639
TI  - A nationwide survey on the expectation of public healthcare providers on family
      medicine specialists in Malaysia-a qualitative analysis of 623 written comments.
AB  - OBJECTIVE: To examine the expectation of public healthcare
      providers/professionals (PHCPs) who are working closely with family medicine
      specialists (FMSs) at public health clinics. DESIGN: Cross-sectional study.
      SETTING: This study is part of a larger national study on the perception of the
      Malaysian public healthcare professionals on FMSs. PARTICIPANTS: PHCPs from three
      categories of health facilities, namely hospitals, health clinics and health
      offices. MAIN OUTCOME MEASURES: Qualitative analysis of written comments of
      respondents' expectation of FMSs. RESULTS: The participants' response rate was
      58% (780/1345) with an almost equal proportion from each public healthcare
      facility. We identified 21 subthemes for the 623 expectation comments. The six
      emerging themes are (1) need for more FMSs, (2) clinical roles and functions of
      FMSs, (3) administrative roles of FMSs, (4) contribution to community and public
      health, (5) attributes improvement and (6) research and audits. FMSs were
      expected to give attention to clinical duty. Delivering this responsibility with
      competence included having the latest medical knowledge in their own and others'
      medical disciplines, practising evidence-based medicine in prehospital and
      posthospital care, better supervision of staff and doctors under their care,
      fostering effective teamwork, communicating more often with hospital specialists
      and making appropriate referral. Expectations ranged from definite and strong for
      more FMSs at the health clinics to low expectation for FMSs' involvement in
      research; to mal-expectation on FMSs' involvement in community and public health
      programmes. CONCLUSIONS: There were some remarkable differences in expectations
      on FMSs from the three different PHCPs. These ranged from being clinically
      competent and administratively available for patients and staff at the health
      clinics, to mal-expectations on FMSs to engage in public health affairs. Relevant
      parties, including FMSs themselves, could take appropriate self-improvement
      initiatives to enhance public practice of family medicine and patient care. TRIAL
      REGISTRATION NUMBER NMRR ID: 08-12-1167.

PMID- 24919640
TI  - Outcomes after corrective surgery for congenital dextro-transposition of the
      great arteries using the arterial switch technique: a protocol for a scoping
      systematic review.
AB  - INTRODUCTION: Dextro-transposition of the great arteries (d-TGA) is a life
      threatening congenital health defect that requires rapid surgery. The most widely
      used approach is the arterial switch operation (ASO) developed by Jatene in the
      1970s. The first set of children who received this intervention are now adults.
      The objective of this scoping review of the literature was to document the short
      term (less than 1 year), medium-term (1-20 years) and long-term (more than 20
      years) outcomes in children who underwent the ASO. Our primary income is
      survival, but we will explore other secondary surgical, cardiovascular,
      reproductive and quality-of-life outcomes. METHODS AND ANALYSES: Using a
      systematic scoping review approach, we will conduct a systematic search of the
      published literature for experimental and observational studies published on
      children who received the ASO intervention for classic d-TGA. We will search
      MEDLINE, Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and
      Allied Health Literature (CINAHL) and Literatura Latino Americana em Ciencias da
      Saude (LILACS) from 1973 (date of the first successful ASO) to February 2014.
      Identified articles will be screened in duplicate and full text for selected
      articles will be retrieved. Data extraction will be carried out in duplicate.
      Discrepancies will be resolved by consensus or by consulting a third author.
      Where possible, proportions will be pooled using the inverse variance method. Our
      findings will be reported according to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational
      studies in Epidemiology (MOOSE) guidelines. ETHICS AND DISSEMINATION: The results
      of this paper will be disseminated as peer-reviewed publications, at conferences
      and at clinical rounds. Our findings may answer important questions for surgeons
      who perform the ASO intervention and for clinicians who take care of patients
      after surgery and throughout their lifespans. TRIAL REGISTRATION NUMBER:
      Prospero/CRD42014007590.

PMID- 24919641
TI  - Reading improvement in English- and Hebrew-speaking children with reading
      difficulties after reading acceleration training.
AB  - A reading acceleration program known to improve reading fluency in Hebrew
      speaking adults was tested for its effect on children. Eighty-nine Hebrew- and
      English-speaking children with reading difficulties were divided into a waiting
      list group and two training groups (Hebrew and English) and underwent 4 weeks of
      reading acceleration training. Results of pre- and post-testing of reading
      abilities point to a significant main effect of the test, demonstrating
      improvements in silent contextual reading speed, reading comprehension, and speed
      of processing in both Hebrew and English training groups as compared to their
      performance before the intervention. This study indicates that the Reading
      Acceleration Program might be an effective program for improving reading
      abilities in children, independent of language. 

PMID- 24919642
TI  - Response to Andrea Tendas et al.'s making quality of life assessment a dashboard
      for patients management.

PMID- 24919643
TI  - Sharks senses and shark repellents.
AB  - Despite over 70 years of research on shark repellents, few practical and reliable
      solutions to prevent shark attacks on humans or reduce shark bycatch and
      depredation in commercial fisheries have been developed. In large part, this
      deficiency stems from a lack of fundamental knowledge of the sensory cues that
      drive predatory behavior in sharks. However, the widespread use of shark
      repellents is also hampered by the physical constraints and technical or
      logistical difficulties of deploying substances or devices in an open-water
      marine environment to prevent an unpredictable interaction with a complex animal.
      Here, we summarize the key attributes of the various sensory systems of sharks
      and highlight residual knowledge gaps that are relevant to the development of
      effective shark repellents. We also review the most recent advances in shark
      repellent technology within the broader historical context of research on shark
      repellents and shark sensory systems. We conclude with suggestions for future
      research that may enhance the efficacy of shark repellent devices, in particular,
      the continued need for basic research on shark sensory biology and the use of a
      multi-sensory approach when developing or deploying shark repellent technology. 

PMID- 24919644
TI  - MTHFR gene polymorphism in acute lymphoblastic leukemia among North Indian
      children: a case-control study and meta-analysis updated from 2011.
AB  - Studies on the association of methylenetetrahydrofolate reductase (MTHFR)
      genotype in childhood acute lymphoblastic leukemia (ALL) have yielded conflicting
      results. The present study examines this association in north Indian children
      with ALL and includes an updated meta-analysis. MTHFR (677 and 1298) genotype of
      children with ALL and healthy adult controls were done by the PCR-restriction
      fragment length polymorphism (PCR-RFLP) method and were compared using various
      models of inheritance. A total of 150 patients and 300 controls were included.
      The 677T allele was found protective (odds ratio (OR) 0.21, 95% confidence
      interval (CI) 0.04-0.94), whereas 1298C allele led to an increase in risk (OR
      4.44, 95% CI 2.19-8.99) of childhood ALL. Meta-analysis included 31 and 27
      studies examining the association of 677 and 1298 genotypes, respectively. The
      677 C -> T polymorphism was protective (OR 0.90, 95% CI 0.82-0.99). Protection
      was more pronounced in folate-sufficient populations as compared with those not
      covered by folate fortification guidelines. The 1298A->C polymorphism was
      associated with a marginal increase in risk (OR 1.19, 95% CI 1.01-1.40).

PMID- 24919645
TI  - Comparison of the performance of Ion Torrent chips in noninvasive prenatal
      trisomy detection.
AB  - Semiconductor high-throughput sequencing, represented by Ion Torrent PGM/Proton,
      proves to be feasible in the noninvasive prenatal diagnosis of fetal
      aneuploidies. It is commendable that, with less data and relevant cost also, an
      accurate result can be achieved owing to the high sensitivity and specificity of
      such kind of technology. We conducted a comparative analysis of the performance
      of four different Ion chips in detecting fetal chromosomal aneuploidies. Eight
      maternal plasma DNA samples, including four pregnancies with normal fetuses and
      four with trisomy 21 fetuses, were sequenced on Ion Torrent 314/316/318/PI chips,
      respectively. Results such as read mapped ratio, correlation coefficient and
      phred quality score were calculated and parallelly compared. All samples were
      correctly classified even with low-throughput chip, and, among the four chips,
      the 316 chip had the highest read mapped ratio, correlation coefficient, mean
      read length and phred quality score. All chips were well consistent with each
      other. Our results showed that all Ion chips are applicable in noninvasive
      prenatal fetal aneuploidy diagnosis. We recommend researchers or clinicians to
      use the appropriate chip with barcoding technology on the basis of the sample
      number. 

PMID- 24919646
TI  - Estimating the costs of opioid abuse and dependence from an employer perspective:
      a retrospective analysis using administrative claims data.
AB  - BACKGROUND: Opioid abuse and dependence is problematic across many age groups,
      including the working-age population and their dependents. Little is known,
      however, about the economic costs of opioid abuse/dependence imposed on
      employers, who pay for a substantial portion of healthcare costs through their
      contributions to employer-sponsored health insurance and are also affected by
      indirect costs such as those due to disability and workplace absenteeism.
      OBJECTIVE: To provide a comprehensive, current estimate of the economic burden of
      prescription opioid abuse/dependence to employers. METHODS: Administrative claims
      from beneficiaries covered by large self-insured companies throughout the USA
      were used to identify patients, including employees and dependents, who were
      diagnosed with opioid abuse and/or dependence ('abusers') between 2006 and 2012.
      Healthcare and work-loss costs for abusers were assessed over a 12-month period
      and compared with those for patients not diagnosed with abuse ('comparison
      patients'), using propensity score matching. RESULTS: 7,658 matched pairs of
      abusers and comparison patients were analysed. Relative to comparison patients,
      abusers had significantly higher annual healthcare resource utilization, leading
      to US$10,627 in per-patient incremental annual healthcare costs. Additionally,
      abusers had US$1,244 in excess annual work-loss costs. Together, this implies an
      employer burden for diagnosed abuse of US$1.71 per member per month. CONCLUSION:
      Opioid abuse/dependence impose a substantial economic burden on employers.

PMID- 24919647
TI  - Effect of dissolved LiCl on the ionic liquid-Au(111) interface: an in situ STM
      study.
AB  - The structure of the electrolyte/electrode interface plays a significant role in
      electrochemical processes. To date, most studies are focusing on understanding
      the interfacial structure in pure ionic liquids. In this paper in situ scanning
      tunnelling microscopy (STM) has been employed to elucidate the structure of the
      charged Au(111)-ionic liquid (1-butyl-1-methylpyrrolidinium
      tris(pentafluoroethyl)trifluorophosphate, [Py1,4]FAP) interface in the presence
      of 0.1 M LiCl. The addition of the Li salt to the ionic liquid has a strong
      influence on the interfacial structure. In the first STM scan in situ
      measurements reveal that Au(111) undergoes the (22 x ?3) 'herringbone'
      reconstruction in a certain potential regime, and there is strong evidence that
      the gold surface dissolves at negative electrode potentials in [Py1,4]FAP
      containing LiCl. Bulk deposition of Li is obtained at -2.9 V in the second STM
      scan.

PMID- 24919648
TI  - Public health ethics and more-than-human solidarity.
AB  - This article contributes to the literature on One Health and public health ethics
      by expanding the principle of solidarity. We conceptualise solidarity to
      encompass not only practices intended to assist other people, but also practices
      intended to assist non-human others, including animals, plants, or places. To
      illustrate how manifestations of humanist and more-than-human solidarity may
      selectively complement one another, or collide, recent responses to Hendra virus
      in Australia and Rabies virus in Canada serve as case examples. Given that caring
      relationships are foundational to health promotion, people's efforts to care for
      non-human others are highly relevant to public health, even when these efforts
      conflict with edicts issued in the name of public health. In its most optimistic
      explication, One Health aims to attain optimal health for humans, non-human
      animals and their shared environments. As a field, public health ethics needs to
      move beyond an exclusive preoccupation with humans, so as to account for moral
      complexity arising from people's diverse connections with places, plants, and non
      human animals. 

PMID- 24919649
TI  - Whose social capital matters? The case of U.S. urban public hospital closures and
      conversions to private ownership.
AB  - Prior literature on social capital and health has predominantly focused on health
      outcomes and individual access to healthcare services. It is not known to what
      degree, if any, community social capital influences the performance or behaviors
      of public hospitals, a key source of healthcare for disadvantaged communities in
      the United States. In this study we developed measures of community bridging
      social capital - horizontal social networks between heterogeneous groups of
      similar social position - and linking social capital - vertical networks across
      the status hierarchy - relevant to public hospitals. We examined associations
      between social capital, and U.S. urban public hospital closures and conversions
      to private ownership from 1987 to 2007. We found that higher voting participation
      was associated with a greater hazard of public hospital closure over time (p <
      0.01), whereas the number of business, professional and political organizations
      per 10,000 residents was associated a greater hazard of conversion (p < 0.05).
      Additional measures of bridging and linking social capital were not associated
      with either outcome. Taken together, our findings suggest that, at least
      historically, horizontal forms of social capital among more privileged groups
      (e.g., business, professional, and political associations) bear influence on
      public hospital outcomes. Specific efforts to increase engagement of
      disadvantaged groups and connect them with decision-makers may be needed to fully
      realize the potential of linking social capital to influence local healthcare
      policy promoting social protection. 

PMID- 24919650
TI  - Novel mutations and clinical outcomes of copper-histidine therapy in Menkes
      disease patients.
AB  - Menkes disease is a very rare X-linked copper metabolism disorder that results
      from an ATP7A gene mutation. With the advent of subcutaneous copper-histidine
      therapy, the early diagnosis of Menkes disease becomes of utmost importance for
      patients' prognosis. In the present study, the clinical characteristics of 12
      Korean patients with Menkes disease (11 males and 1 female from 11 unrelated
      families) were described along with the mutation spectrum. Only 2 male patients
      were diagnosed in the neonatal period, and the other male patients were diagnosed
      at age 4.3 +/- 1.9 months. The presenting signs included depigmented kinky hair,
      neurologic deficits, and hypotonia. Serum copper and ceruloplasmin levels were
      markedly decreased. Intracranial vessels were dilated with tortuosity and
      accompanied by regional cerebral infarctions, even at an early age. Of note, the
      female patient was diagnosed at age 18 months, during the evaluation for
      developmental delay, by characteristic MRA findings, biochemical profiles, and
      genetic evaluation. A total of 11 ATP7A mutations were identified, including five
      previously unreported mutations. Most mutations were truncated (except 1 missense
      mutation), including 3 frameshift, 2 nonsense, 3 large deletion, and 2 splice
      site variants. The age at commencement of copper-histidine treatment was variable
      among patients age 7.3 +/- 7.5 (0.5-27) months. Despite the treatment, seven
      patients died before age 5 years, and the remaining patients were severely
      retarded in neurodevelopment. The poor outcomes of our patients might be related
      to delayed therapy, but severe ATP7A mutations should be noted as well.

PMID- 24919651
TI  - Glycyrrhizin suppresses HMGB1 inductions in the hippocampus and subsequent
      accumulation in serum of a kainic acid-induced seizure mouse model.
AB  - Glycyrrhizin (GL), a triterpene present in the roots and rhizomes of licorice
      (Glycyrrhiza glabra), has been shown to have anti-inflammatory and anti-viral
      effects. In our previous reports, we demonstrated the neuroprotective effects of
      GL in the postischemic brain and in kainic acid (KA)-induced seizure animal
      model. In this KA-induced seizure model, the systemic administration of GL 30 min
      before KA administration significantly suppressed neuronal cell death and
      markedly suppressed gliosis and proinflammatory marker inductions. In the present
      study, we showed that high-mobility group box 1 (HMGB1), an endogenous danger
      signal, was induced in hippocampal CA1 and CA3 regions of the same KA-induced
      model, and peaked at ~3 h and at 6 days post-KA. HMGB1 was transiently induced in
      neurons and astrocyte at 3 h post-KA, and it was released from dying neurons and
      accumulated in serum at 12 h post-KA. Furthermore, after ~4 days of almost
      undetectable levels in the hippocampus, delayed and marked HMGB1 induction was
      detected at 6 days post-KA, mainly in astrocytes and endothelial cells, in which
      HMGB1 was localized in nuclei, and not secreted into serum. Interestingly, GL
      suppressed HMGB1 inductions in hippocampus and also suppressed its release into
      serum in KA-treated mice. Since we established previously that GL has anti
      inflammatory and anti-excitotoxic effects in this KA-induced seizure model, these
      results indicate that the neuroprotective effect of GL in the KA-injected mouse
      brain might be attributable to the inhibitions of HMGB1 induction and release,
      which in turn, mitigates the inflammatory process.

PMID- 24919652
TI  - Child-care subsidies and child-care choices over time.
AB  - The evidence to date on the federal child-care subsidy program's effect on
      preschool child-care quality is mixed. However, an as-yet untested outcome of
      subsidy receipt is subsequent child-care choice. Specifically, it is possible
      that subsidy receipt in toddlerhood increases the likelihood of attending other
      publicly funded preschool programs-Head Start and public pre-k-that provide the
      highest quality care available to low-income families. Using data from the Early
      Childhood Longitudinal Study-Birth Cohort (n ~ 2,100; approximately 2 years old),
      this study finds that subsidy receipt during toddlerhood predicts greater use of
      the other forms of publicly funded care in the preschool year, although only if
      the earlier subsidy is used in a center. These results highlight a previously
      unconsidered potential benefit of the subsidy program. 

PMID- 24919653
TI  - Comparing amyloid-beta deposition, neuroinflammation, glucose metabolism, and
      mitochondrial complex I activity in brain: a PET study in aged monkeys.
AB  - PURPOSE: The aim of the present study was to compare amyloid-beta (Abeta)
      deposition, translocator protein (TSPO) activity, regional cerebral metabolic
      rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the
      brain of aged monkeys. METHODS: PET scans with (11)C-PIB (Abeta), (18)F-BCPP-EF
      (MC-I), (11)C-DPA-713 (TSPO), and (18)F-FDG (rCMRglc) were performed in aged
      monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia.
      (11)C-PIB binding to Abeta and (11)C-DPA-713 binding to TSPO were evaluated in
      terms of standard uptake values (SUV). The total volume of distribution (V T) of
      (18)F-BCPP-EF and rCMRglc with (18)F-FDG were calculated using arterial blood
      sampling. RESULTS: Isoflurane did not affect MC-I activity measured in terms of
      (18)F-BCPP-EF uptake in living brain. There was a significant negative
      correlation between (18)F-BCPP-EF binding (V T) and (11)C-PIB uptake (SUVR), and
      there was a significant positive correlation between (11)C-DPA-713 uptake (SUV)
      and (11)C-PIB uptake. In contrast, there was no significant correlation between
      rCMRglc ratio and (11)C-PIB uptake. CONCLUSION: (18)F-BCPP-EF could be a
      potential PET probe for quantitative imaging of impaired MC-I activity that is
      correlated with Abeta deposition in the living brain.

PMID- 24919654
TI  - Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic
      cancer patients.
AB  - Telomerase is expressed in 85-90 % of pancreatic adenocarcinomas and might be a
      target for active cancer immunotherapy. A study was conducted to investigate
      safety and immunogenicity in non-resectable pancreatic carcinoma patients using a
      16-amino acid telomerase peptide (GV1001) for vaccination in combination with GM
      CSF and gemcitabine as first line treatment. Three different vaccine treatment
      schedules were used; [A (n=6), B (n=6) and C (n=5)]. Groups A/B received GV1001,
      GM-CSF and gemcitabine concurrently. Group C received initially GV1001 and GM-CSF
      while gemcitabine was added at disease progression. Group D (n=4) was treated
      with gemcitabine alone. Adverse events (AE) related to vaccination were mild
      (grades I-II). Grade III AEs were few and transient. An induced GV 1001-specific
      immune response was defined as an increase >=2 above the baseline value in one of
      the assays (DTH, proliferation, ELISPOT and cytokine secretion assays,
      respectively). A telomerase-specific immune response was noted in 4/6 patients in
      group A, 4/6 patients in group B and 2/5 patients in group C. An induced ras
      specific immune response (antigenic spreading) was seen in 5 of the 17 patients.
      The cytokine pattern was that of a Th1-like profile. A treatment induced
      telomerase or ras response was also noted in group D. All responses were weak and
      transient. A significant decrease in regulatory T-cells over time was noted in
      patients in groups A and B (p<0.05). Telomerase vaccination (GV1001) in
      combination with chemotherapy appeared to be safe but the immune responses were
      weak and transient. Measures have to be taken to optimize immune responses of
      GV1001 for it to be considered of clinical interest.

PMID- 24919655
TI  - Influence of crown-to-implant ratio on stress around single short-wide implants:
      a photoelastic stress analysis.
AB  - PURPOSE: The aim of this study was to evaluate the photoelastic fringe patterns
      around two short-wide implants supporting single crowns with different crown-to
      implant (C/I) ratios. MATERIALS AND METHODS: External hexagon (EH) cylindrical
      implants (5 * 7 mm) or Morse Taper (MT) conical implants (5 * 6 mm) were embedded
      individually into photoelastic resin blocks. Each implant received a single metal
      ceramic crown, with a C/I ratio of 1:1 or 2:1 (n = 10). Each set was positioned
      in a polariscope and submitted to a 0.5 kgf compressive load, applied axially or
      obliquely (30 degrees ). The polariscope images were digitally recorded, and
      based on isoclinal and isochromatic fringes, the shear stress was calculated at 5
      predetermined points around each implant. Data were analyzed by two-way ANOVA
      (alpha = 0.05). RESULTS: Under axial loading, the stress was concentrated at the
      crestal region, and there were no differences between C/I ratio or implant types.
      In contrast, under oblique loading, EH implants showed lower stress values than
      the MT group and the 2:1 C/I ratio showed higher stress concentration for both
      implant types (p < 0.05). Moreover, MT implants showed stress distribution
      through a higher area than the EH implant did, with a tendency to direct the
      stress toward the implant's apex under oblique loading. CONCLUSION: MT conical
      short-wide implants showed higher stress values that were distributed through a
      higher area directed to the implant apex. The C/I ratio influences the stress
      distribution only under oblique loading.

PMID- 24919656
TI  - Diabetes mellitus induced impairment of male reproductive functions: a review.
AB  - Diabetes mellitus (DM) represents one of the greatest threats to human health all
      over the world. The incidence of DM is rising rapidly also including children and
      young persons of reproductive age. Diabetes has been associated with reproductive
      impairment in both men and women. Diabetes may affect male reproductive functions
      at multiple levels as a result of its effects on the endocrine control of
      spermatogenesis, steroidogenesis, sperm maturation, impairment of penile erection
      and ejaculation. A large number of studies both on diabetic men and experimental
      diabetic animals have been published on the impact of DM on male reproductive
      functions during the past few years but many of them have conflicting results.
      The present review summarizes the research finding of a large number of research
      papers on the reproductive functions especially on hypothalmo-pituitary-gonadal
      axis, spermatogenesis, histopathology of testis, synthesis and secretion of
      testosterone, sperm quality, ejaculatory function and fertility both in diabetic
      men and experimental diabetic animals. 

PMID- 24919657
TI  - Hyperglycemia to nephropathy via transforming growth factor beta.
AB  - Nephropathy is one of the major complications of diabetes which further directs
      to end stage renal disease. Extensive work has been done to find out the
      mechanisms involved in pathogenesis of the DN. Now, many researchers have been
      convinced that almost all of the molecular mediators and intracellular signaling
      pathways involved in progression of diabetic nephropathy have involvement in
      transforming growth factor beta (TGF- beta) at some stage. In DN, hyperglycemia
      causes increase in the expression of TGF- beta genes, TGF- beta proteins and
      their receptors. Increased glucose level mediates these effects through
      activation of polyol pathway, protein kinase C pathway, hexosamine pathway,
      increases advanced glycation end products (AGE) and increases oxidative stress.
      Hyperglycemia also activates the TGF- beta via activation of glucose transporters
      (GLUT), angiotensine II and platelet derived growth factor (PDGF). Activated TGF
      beta further leads to glomerular basement membrane (GBM) thickening and
      glomerulosclerosis through activation of connective tissue growth factor (CDGF)
      and vascular endothelial growth factor (VEGF). We have discussed the progression
      of hyperglycemia to DN via TGF- beta, whose schematic presentation may serve as
      an effective way to understand the mechanisms and to find out an effective way
      for the management of diabetic nephropathy. 

PMID- 24919658
TI  - Web services-based text-mining demonstrates broad impacts for interoperability
      and process simplification.
AB  - The Critical Assessment of Information Extraction systems in Biology
      (BioCreAtIvE) challenge evaluation tasks collectively represent a community-wide
      effort to evaluate a variety of text-mining and information extraction systems
      applied to the biological domain. The BioCreative IV Workshop included five
      independent subject areas, including Track 3, which focused on named-entity
      recognition (NER) for the Comparative Toxicogenomics Database (CTD;
      http://ctdbase.org). Previously, CTD had organized document ranking and NER
      related tasks for the BioCreative Workshop 2012; a key finding of that effort was
      that interoperability and integration complexity were major impediments to the
      direct application of the systems to CTD's text-mining pipeline. This underscored
      a prevailing problem with software integration efforts. Major interoperability
      related issues included lack of process modularity, operating system
      incompatibility, tool configuration complexity and lack of standardization of
      high-level inter-process communications. One approach to potentially mitigate
      interoperability and general integration issues is the use of Web services to
      abstract implementation details; rather than integrating NER tools directly, HTTP
      based calls from CTD's asynchronous, batch-oriented text-mining pipeline could be
      made to remote NER Web services for recognition of specific biological terms
      using BioC (an emerging family of XML formats) for inter-process communications.
      To test this concept, participating groups developed Representational State
      Transfer /BioC-compliant Web services tailored to CTD's NER requirements.
      Participants were provided with a comprehensive set of training materials. CTD
      evaluated results obtained from the remote Web service-based URLs against a test
      data set of 510 manually curated scientific articles. Twelve groups participated
      in the challenge. Recall, precision, balanced F-scores and response times were
      calculated. Top balanced F-scores for gene, chemical and disease NER were 61, 74
      and 51%, respectively. Response times ranged from fractions-of-a-second to over a
      minute per article. We present a description of the challenge and summary of
      results, demonstrating how curation groups can effectively use interoperable NER
      technologies to simplify text-mining pipeline implementation. Database URL:
      http://ctdbase.org/ 

PMID- 24919659
TI  - Echocardiographic analysis of an extracellular matrix tricuspid valve.

PMID- 24919661
TI  - Social support and depressive symptoms among 'money' boys and general men who
      have sex with men in Shanghai, China.
AB  - The primary objective was to examine prevalence and correlates of social support
      and depressive symptoms among male sex workers (known as 'money boys' (MBs)) and
      general men who have sex with men (MSM) in Shanghai. The Social Provision Scale
      (SPS), which consists of 24 items, scored out of 4 for social provision, was used
      to evaluate the functions of social relationships. The score for each item ranges
      from 1 to 4, with a higher score indicating more social provision. The overall
      mean SPS score was 68.1 (s.d.=6.53) for MBs and 69.3 (s.d.=6.99) for general MSM.
      Depression was measured with a 12-item version of the Center for Epidemiological
      Studies Depression Scale (CES-D), where a score of 9 has been recommended as the
      cutoff score to indicate possible depressive symptoms. The prevalence of
      depressive symptoms was 57.9%, with MBs having a higher level of depressive
      symptoms than general MSM (70.0% v. 46.1%) (odds ratio=1.86, 95% confidence
      interval=1.07-3.24). Social support was a protective factor for depressive
      symptoms (odds ratio=0.92, 95% confidence interval=0.89-0.96). MSM in China,
      particularly MBs, are vulnerable to low social support and high depressive
      symptoms, highlighting the need for tailored psychological programs targeting
      this population. 

PMID- 24919660
TI  - Fractures are increased and bisphosphonate use decreased in individuals with
      insulin-dependent diabetes: a 10 year cohort study.
AB  - BACKGROUND: Individuals with diabetes have been found previously to be at
      increased risk of non-traumatic fracture. However, it is unclear if these
      individuals are being identified and treated for osteoporosis. METHODS: 7753
      Canadians over 50 years of age were followed prospectively for 10 years. 606/7753
      (7.8%) of had diabetes; 98 were insulin-dependent and 508 were not. Using a cox
      proportional hazards model, we assessed the association between diabetes status
      and incident non-traumatic fracture. Using logistic regression we identified
      factors associated with bisphosphonate use over the 10 year period of study.
      RESULTS: Mean (SD) age of participants was 66.7(9.4) years and 72% were female.
      Those with diabetes had higher BMD T-scores at baseline, with a mean (SD) femoral
      neck T-Score of -0.97 (1.06), compared to -1.24 (0.99) in the general cohort. The
      adjusted hazard ratio (HR) for incident non-traumatic fracture in individuals
      with insulin-dependent diabetes over the 10 year study period was 2.50 (95%
      confidence interval [CI] 1.60, 3.90; p < 0.001). Despite this increased fracture
      rate, individuals with diabetes (insulin-dependent or non-insulin-dependent) were
      less likely to be on bisphosphonate therapy at any point over 10 years of
      prospective follow up compared to other CaMos subjects (odds ratio [OR]: 0.59;
      95% CI 0.46-0.75, p < 0.001). CONCLUSIONS: Despite the increased risk of non
      traumatic fracture associated with insulin-dependent diabetes, we that found
      individuals with diabetes are less likely to be treated with a bisphosphonate
      than those without diabetes. These findings point to a possible care gap in the
      treatment of non-traumatic fractures in individuals with diabetes in Canada.

PMID- 24919662
TI  - Screening of blood donors for chronic Coxiella burnetii infection after large Q
      fever outbreaks.
AB  - BACKGROUND: The Netherlands experienced major Q fever outbreaks from 2007 through
      2009. An increasing number of human chronic Q fever cases has been reported in
      the affected area. Blood donors unaware of chronic Coxiella burnetii infection
      might be infectious for transfusion recipients. Local blood donations were
      screened for serologic signs of chronic Coxiella infection. STUDY DESIGN AND
      METHODS: From August 2012 through January 2013, a total of 2490 serum samples
      were collected from all consenting blood donors in the most affected Q fever
      outbreak area and screened for Phase II anti-Coxiella immunoglobulin G antibodies
      using an enzyme-linked immunosorbent assay (ELISA). (Phase II antibodies are
      considered indicative for resolved or ongoing Coxiella infection.) Reactive
      samples were confirmed by quantitative immunofluorescent Phase I and II antibody
      testing. A Phase I antibody titer of at least 1024 was considered indicative for
      chronic Coxiella infection. For 179 donors archived samples from 2009 and 2010
      were available to study the long-term course of Coxiella antibodies. RESULTS: A
      total of 110 of 2490 donors were confirmed positive for Phase II Coxiella
      antibodies (4.4%; 95% confidence interval, 3.7%-5.3%), of which 79 were reactive
      for Phase I antibodies, with a maximum titer of 256. In 15 of 24 donors (62.5%),
      testing positive for Phase II antibodies in 2009 and 2010, ELISA reactivity had
      declined to negativity in 2012 and 2013. CONCLUSION: After large Q fever
      outbreaks in the Netherlands, no sign of potentially infectious chronic Coxiella
      infection was found among blood donors in the most affected area. Using an ELISA
      for detection, Coxiella antibodies in previously exposed donors waned quickly.

PMID- 24919663
TI  - Biosynthesis of Nudicaulins: A (13) CO2 -pulse/chase labeling study with Papaver
      nudicaule.
AB  - Nudicaulins are unique alkaloids responsible for the yellow color of the petals
      of some papaveraceaous plants. To elucidate the unknown biosynthetic origin of
      the skeleton, a (13) CO2 -pulse/chase experiment was performed with growing
      Papaver nudicaule plants. (13) C NMR analysis revealed more than 20 multiple (13)
      C-enriched isotopologues in nudicaulins from the petals of (13) CO2 -labeled
      plants. The complex labeling pattern was compared with the isotopologue
      composition of a kaempferol derivative that was isolated from petals of the same
      (13) CO2 -labeled plants. The deconvolution of the labeling profiles indicated
      that the nudicaulin scaffold is assembled from products or intermediates of
      indole metabolism, the phenylpropanoid pathway, and the polyketide biosynthesis.
      Naringenin-type compounds and tryptophan/tryptamine are potential substrates for
      the condensation reaction finally generating the aglycone skeleton of
      nudicaulins. 

PMID- 24919664
TI  - Brief overview on 2H NMR studies of polysiloxane-based side-chain nematic
      elastomers.
AB  - This is a brief overview on recent studies on liquid crystalline elastomers
      (LCEs) based on polysiloxane chain, in the form of monodomain films, selectively
      (2)H-labeled in different parts of the LCE samples, i.e. on the crosslinker or
      mesogenic units. (2)H NMR spectroscopic techniques were used to measure the
      temperature dependence of the quadrupolar splittings, line widths and relaxation
      times, T(1) and T(2). From these data, several information about the
      orientational order parameter, S, of various LCE fragments, thermodynamic
      features of the isotropic-nematic transition and main motional processes could be
      generalized for this type of elastomers.

PMID- 24919666
TI  - PNA-tagged peptide microarrays for ratiometric activity detection of cellular
      protein kinases.
AB  - Peptide microarrays can be used to measure the activity of multiple protein
      kinases (PKs), which can be used to elucidate kinomics for drug discovery and
      diagnosis. Here we demonstrated a new microarray for ratiometric detection of the
      activity of PKs using peptide nucleic acid (PNA)-tagged peptides labeled with two
      different fluorophores, Cy3 and Cy5. We successfully detected cellular PK
      activities based on ratiometry, and applied the system for evaluation of an
      inhibitory drug. 

PMID- 24919667
TI  - Simultaneous detection of nucleic acid and protein using gold nanoparticles and
      lateral flow device.
AB  - In this work, we present a simple and fast approach for simultaneous detection of
      nucleic acid and protein using gold nanoparticles (GNPs) and a lateral flow
      device (LFD). Sandwich-type immunoreactions and DNA hybridizations were performed
      simultaneously on the LFD by using DNA- and antibody-functionalized GNPs. The
      captured GNPs, due to the DNA hybridization and immunoreaction events on the LFD,
      produced characteristic red bands that could be used for the qualitative
      detections of DNA and/or protein. The proof of principle was demonstrated by
      using 60-mer DNA and rabbit IgG (R-IgG) model targets. The LFD was capable of
      detecting a minimum of 0.5 nM target DNA and 2 ng mL(-1) IgG simultaneously in 15
      min. The proposed LFD shows great promise for in-field and point-of-care testing
      of disease-related circulating nucleic acid and protein biomarkers in biological
      fluids. 

PMID- 24919668
TI  - Effects of cyclodextrins on intramolecular photoinduced electron transfer in a
      boronic acid fluorophore.
AB  - An inclusion complex consisting of a boronic acid fluorophore (C1-APB) and beta
      cyclodextrin (beta-CyD) acts as a supramolecular sugar sensor whose response
      mechanism is based on photoinduced electron transfer (PET) from the excited
      pyrene to the boronic acid. We have investigated the PET process in C1-APB/CyD
      complexes by using time-resolved photoluminescence (TRPL) measurements at room
      temperature, and have succeeded in estimating the electron-transfer time to be
      about 1 ns. We have also studied the effects of CyDs on the PET process by
      comparing two kinds of CyDs (alpha-CyD, beta-CyD) under different water
      dimethyisulfoxide (DMSO) concentration conditions. We found that the CyDs
      interacting with the boronic acid moiety completely inhibits PET quenching and
      increases the monomer fluorescence intensity. 

PMID- 24919669
TI  - Construction of an electrode modified with gallium(III) for voltammetric
      detection of ovalbumin.
AB  - Electrodes modified with gallium(III) complexes were constructed to detect
      ovalbumin (OVA). For immobilization of a gallium(III)-nitrilotriacetate (NTA)
      complex, the electrode was first covered with collagen film. After the amino
      groups of the film had reacted with isothiocyanobenzyl-NTA, the gallium(III) was
      then able to combine with the NTA moieties. Another design featured an electrode
      cast with a gallium(III)-acetylacetonate (AA) complex. The amount of gallium(III)
      in the NTA complex was equivalent to one-quarter of the gallium(III) that could
      be utilized from an AA complex. However, the calibration curves of OVA using
      gallium(III)-NTA and gallium(III)-AA complexes were linear in the ranges of 7.0 *
      10(-11) - 3.0 * 10(-9) M and 5.0 * 10(-10) - 8.0 * 10(-9) M, respectively. The
      gallium(III) on the electrode with NTA complex had high flexibility due to the
      existence of a spacer between the NTA and the collagen film, and, therefore, the
      reactivity of the gallium(III) to OVA was superior to that of the gallium(III)-AA
      complex with no spacer. 

PMID- 24919670
TI  - A spectrophotometric procedure for malic acid determination in wines employing a
      multicommutation approach.
AB  - This work describes an automated procedure to determine L-malic acid (MA) in wine
      samples using a multicommuted flow analysis. The MA quantification was based on
      an enzymatic reaction between MA and L-malate dehydrogenase (L-MDH) in the
      presence of nicotinamide adenine dinucleotide (NAD(+)), producing nicotinamide
      adenine dinucleotide dehydrogenase (NADH), which was monitored at 340 nm. The L
      MDH was immobilized on a surface of modified silica with amino groups in the
      presence of glutaraldehyde. For studying optimization, the system was maintained
      with 200 MUL (288 U) of the L-MDH in 0.5 g of modified silica. Under the optimum
      experimental conditions, a linear response ranging from 0.1 to 1.5 g L(-1) MA (R
      = 0.997 and n = 7), a detection (3sigma criterion) and quantification (10sigma
      criterion) limit estimated at 0.02 and 0.06 g L(-1), respectively, a standard
      deviation relative of 1.8% (n = 7) for a sample of 0.5 g L(-1) MA, a sampling
      rate of 67 samples per hour were achieved. Analyzing ten wines samples and
      applying the t-test to the results found and those obtained using reference
      procedures (HPLC) provided no significant differences at the 95% confidence
      level. 

PMID- 24919671
TI  - Preparation of a magnetic metal organic framework composite and its application
      for the detection of methyl parathion.
AB  - A magnetic metal organic framework (MOF) composite was prepared. The composite
      was fabricated by incorporation of Fe3O4 nanoparticals with MOF. It was
      characterized and expected to offer a promising template for molecular
      immobilization and sensor fabrication because of its ordered structure and
      satisfying large specific surface area. The resulting composite was used to
      detect methyl parathion. Electrochemical measurements showed that the
      multifunctional composite of MOF provided an excellent matrix for the co
      adsorption of methyl parathion. Owing to the ordered structure, the large surface
      area, excellent compatibility and magnetic property of the material, methyl
      parathion could be separated, accumulated and directly detected in the solution
      with high sensitivity. The differential pulse voltammetry (DPV) response was
      proportional to the concentration range from 5.00 * 10(-6) to 5.00 * 10(-3) g L(
      1) with the detection limit of 3.02 * 10(-6) g L(-1). The experimental results
      can lead to a widespread use of electrochemical sensors to detect
      organophosphorous pesticides contaminates and other substances. 

PMID- 24919672
TI  - A sensitive amperometric acetylcholine biosensor based on carbon nanosphere and
      acetylcholinesterase modified electrode for detection of pesticide residues.
AB  - A sensitive biosensor based on acetylcholinesterase (AChE) and carbon nanosphere
      (CNS) immobilized on a glassy carbon electrode was developed for the detection of
      pesticides by the inhibition of AChE activity. The inhibition effect of the
      pesticides resulted in a decrease of current response of the acetylthiocholine
      chloride that was used as a substrate to obtain an electrochemical signal. When
      applied to the pesticides carbofuran and fenitrothion, the designed biosensor
      exhibited high sensitivity and low detection limits. The inhibition ratio of
      carbofuran and fenitrothion were linearly proportional to their concentrations
      ranging from 0.40 to 4.79 and 6.26 to 125.31 MUg/L, respectively. The theoretical
      detection limits were found to be 0.082 MUg/L for carbofuran and 2.61 MUg/L for
      fenitrothion. Furthermore, as the biosensor offers good reproducibility and
      stability, it could be used for trace detection of pesticides in real samples.
      Compared with other AChE biosensors, the proposed biosensor was convenient and it
      exhibited extreme sensitivity to pesticides. 

PMID- 24919673
TI  - Electrophoretic separation of chlorophenols on silica nanospheres-coated
      poly(dimethylsiloxane) microchip using a Nafion/graphene-modified carbon
      electrode for detection.
AB  - In the present work, the micellar electrophoretic separation of five
      chlorophenols (CPs) on a functionalized poly(dimethylsiloxane) (PDMS) microchip
      with amperometric detection was performed. In order to achieve high resolution by
      controlling the electroosmotic flow (EOF) as well as signal detection by
      suppressing analytes adsorption, the microchannel was functionalized by
      poly(diallyldimethylammonium chloride) (PDDA)/SiO2 nanospheres (NSs)/ poly(sodium
      p-styrenesulfonate) (PSS), via an approach of layer-by-layer assembly. Five
      chlorophenols (2-chlorophenol, 4-chlorophenol, 2,4-dichlorophenol, 2,3
      dichlorophenol and 2,4,6-trichlorophenol) were efficiently separated in this
      microchannel (3.7 cm of length) within 120 s. A resolution of at least 2.4 was
      obtained with a 10 mM phosphate buffer solution (PBS) (pH 9.48) containing 20 mM
      sodium dodecyl sulfate (SDS) and 50% (v/v) acetonitrile as a carrier under
      optimized conditions. A graphene-modified carbon microdisk electrode was used for
      high-sensitivity detection. Its characteristics were investigated by cyclic
      voltammetry (CV) and electrochemical impedance spectroscopy (EIS). For those CPs,
      linear ranges of 0.08-5, 0.06-5, 0.04-5, 0.04-5 and 0.30-20 MUM and detection
      limits of 0.021, 0.026, 0.022, 0.019 and 0.054 MUM were obtained, respectively.
      The method was successfully applied for the analysis of some wastewater samples
      with satisfactory recovery.

PMID- 24919674
TI  - Visual detection of arsenic using hydride generation followed by reaction with
      silver bis(2-ethylhexyl)dithiocarbamate retained in a support filter.
AB  - In this study, a simple and effective method for the detection of trace amounts
      of arsenic in water samples was developed. Arsenic hydride generated by the
      reduction of a water sample was passed through a sensing filter retaining silver
      bis(2-ethylhexyl)dithiocarbamate complex. The original yellow color of the filter
      immediately turned reddish violet. The difference of color was observed by a
      reflection spectrophotometer. Sensing filters made of glass fiber gave the
      highest sensitivity. Addition of low volatile amines effectively stabilized the
      performance of the sensing filter. Common anions including phosphate ion did not
      interfere with the arsenic detection. Visual detection of 10 MUg dm(-3) was
      achieved in phi10 mm filter area using 60 cm(3) of sample solution.

PMID- 24919675
TI  - Tube radial distribution phenomenon with a two-phase separation solution of a
      fluorocarbon and hydrocarbon organic solvent mixture in a capillary tube and
      metal compounds separation.
AB  - A fluorocarbon and hydrocarbon organic solvent mixture is known as a temperature
      induced phase-separation solution. When a mixed solution of tetradecafluorohexane
      as a fluorocarbon organic solvent and hexane as a hydrocarbon organic solvent
      (e.g., 71:29 volume ratio) was delivered in a capillary tube that was controlled
      at 10 degrees C, the tube radial distribution phenomenon (TRDP) of the solvents
      was clearly observed through fluorescence images of the dye, perylene, dissolved
      in the mixed solution. The homogeneous mixed solution (single phase) changed to a
      heterogeneous solution (two phases) with inner tetradecafluorohexane and outer
      hexane phases in the tube under laminar flow conditions, generating the dynamic
      liquid-liquid interface. We also tried to apply TRDP to a separation technique
      for metal compounds. A model analyte mixture, copper(II) and hematin, was
      separated through the capillary tube, and detected with a chemiluminescence
      detector in this order within 4 min. 

PMID- 24919676
TI  - Stability study of the antihistamine drug azelastine HCl along with a kinetic
      investigation and the identification of new degradation products.
AB  - The first stability-indicating HPLC method was developed and validated for
      azelastine HCl (AZL). The separation of AZL from its degradation products was
      achieved on a C18 column using acetonitrile-0.04 M phosphate buffer of pH 3.5
      (32:68, v/v) as a mobile phase with UV-detection at 210 nm and naftazone as an
      internal standard. The method was rectilinear over the range of 0.2-20.0 MUg mL(
      1) with a detection limit of 7.05 ng mL(-1). The degradation behavior of AZL was
      studied under different ICH-recommended stress conditions along with a kinetic
      investigation; also, degradation products were identified by mass spectrometry.
      The method was applied for the quality control and stability assessment of AZL in
      eye drops and nasal spray. The obtained results were favorably compared with
      those obtained by a comparison method.

PMID- 24919678
TI  - A meta-substrate to enhance the bandwidth of metamaterials.
AB  - We propose the concept of a meta-substrate to broaden the bandwidth of left
      handed metamaterials. The meta-substrate, which behaves like an inhomogeneous
      magnetic substrate, is composed of another kind of magnetic metamaterials like
      metallic closed rings. When conventional metamaterial rings are printed on this
      kind of meta-substrate in a proper way, the interaction of the metamaterials
      units can be greatly enhanced, yielding an increased bandwidth of negative
      permeability. An equivalent circuit analytical model is used to quantitatively
      characterize this phenomenon. Both numerical and experimental demonstrations are
      carried out, showing good agreement with theoretical predictions. 

PMID- 24919679
TI  - Anisotropic dissymmetry factor, g: theoretical investigation on single molecule
      chiroptical spectroscopy.
AB  - A formula for an anisotropic dissymmetry factor g evaluating the chiroptical
      response of orientationally fixed molecules is derived. Incorporating zeroth- and
      first-order multipole expansion terms, it is applied to bridged triarylamine
      helicene molecules to examine the experimental results of single-molecule
      chiroptical spectroscopy. The ground- and excited-state wave functions and a
      series of transition moments required for the evaluation of the anisotropic g
      value are calculated using time-dependent density functional theory (TDDFT). The
      probability histograms obtained for simulated g values, uniformly sampled in
      regard to the direction of light propagation toward the fixed molecule, show that
      even for a given diastereomer, the dissymmetry factors have positive and negative
      values and can deviate from their averages to a considerable extent when the
      angle between the electric dipole transition moment and the propagation vector of
      the incident light is near 0 or 180 degrees . 

PMID- 24919680
TI  - Application of cell sheet technology to bone marrow stromal cell transplantation
      for rat brain infarct.
AB  - Bone marrow stromal cells (BMSC) transplantation enhances functional recovery
      after cerebral infarct, but the optimal delivery route is undetermined. This
      study was aimed to assess whether a novel cell-sheet technology non-invasively
      serves therapeutic benefits to ischemic stroke. First, the monolayered cell sheet
      was engineered by culturing rat BMSCs on a temperature-responsive dish. The cell
      sheet was analysed histologically and then transplanted onto the ipsilateral
      neocortex of rats subjected to permanent middle cerebral artery occlusion at 7
      days after the insult. Their behaviours and histology were compared with those in
      the animals treated with direct injection of BMSCs or vehicle over 4 weeks post
      transplantation. The cell sheet was 27.9 +/- 8.0 MUm thick and was composed of
      9.8 +/- 2.4 * 105 cells. Cell sheet transplantation significantly improved motor
      function when compared with the vehicle-injected animals. Histological analysis
      revealed that the BMSCs were densely distributed to the neocortex adjacent to the
      cerebral infarct and expressed neuronal phenotype in the cell sheet-transplanted
      animals. These findings were almost equal to those for the animals treated with
      direct BMSC injection. The attachment of the BMSC sheet to the brain surface did
      not induce reactive astrocytes in the adjacent neocortex, although direct
      injection of BMSCs profoundly induced reactive astrocytes around the injection
      site. These findings suggest that the BMSCs in cell sheets preserve their
      biological capacity of migration and neural differentiation. Cell-sheet
      technology may enhance functional recovery after ischaemic stroke, using a less
      invasive method. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24919681
TI  - "Microscopic evidences of heavy metals distribution and anatomic alterations in
      breaching-leaves of Cupressus lindleyi growing around mining wastes".
AB  - In this article a study of the distribution of heavy metals in Cupressus lindleyi
      breaching-leaves was done in Taxco, Guerrero. At the same, heavy metals micro
      localization was conducted in the breaching-leaves to understand the structural
      changes provoked by mining waste on plants. The most abundant contaminants in
      soils, tailings and different plant organs (roots, stems, and leaves) were Zn,
      Mn, and Pb. Nevertheless, As was more accumulated in the stem and breaching
      leaves. The translocation factor and the bio-concentration factor were less than
      1. The structural changes observed were the great accumulation of starch grains
      and phenolic compounds in the palisade parenchyma, changes in the hypodermis cell
      wall and necrotic zones in the palisade parenchyma. The distribution of heavy
      metals in breaching-leaves tissues was homogeneous in most of the elements. These
      results showed that C. lindleyi is a species that can be employed in
      phytostabilization of contaminated zones with mining waste because it is a native
      plant that does not require a lot of conditions for its development.

PMID- 24919682
TI  - Central blood pressure reflects left ventricular load, while brachial blood
      pressure reflects arterial damage.
AB  - OBJECTIVES: The present study investigated whether brachial and central blood
      pressures have differential impact on the cardiovascular system in the general
      population. METHODS: The study included 706 subjects (59 +/- 10 years) who
      visited our hospital for a physical check-up. Brachial blood pressure and radial
      artery pressure waveforms were recorded using an automated device, and the
      pressure corresponding to the radial late systolic peak (SBP2) was taken as
      central blood pressure. The concentration of B-type natriuretic peptide and the
      intima-media thickness of the carotid artery were measured and a cross-sectional
      analysis was performed. RESULTS: Brachial blood pressure was 128 +/- 18/74 +/- 12
      (mean blood pressure, 92 +/- 13) mmHg and SBP2 was 120 +/- 19 mmHg. Although both
      brachial systolic blood pressure and SBP2 correlated with B-type natriuretic
      peptide in a univariate analysis, only SBP2 independently correlated with B-type
      natriuretic peptide after adjustment for possible factors. In contrast, brachial
      systolic blood pressure, but not SBP2, independently correlated with carotid
      artery intima-media thickness. CONCLUSIONS: Central blood pressure is more
      closely associated with left ventricular load than brachial blood pressure, while
      brachial blood pressure is more strongly associated with vascular damage than
      central blood pressure.

PMID- 24919683
TI  - Old tool - new application: NT-proBNP in fetal medicine.

PMID- 24919684
TI  - Furosemide and albumin for diuresis of edema (FADE): a study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Fluid retention is a common complication of critical illness. It
      typically results from large-volume fluid infusions during acute resuscitation
      and is worsened by hypoalbuminemia. Recognized as edema, fluid retention is
      important for its association with delayed weaning and increased mortality. The
      standard treatment is the administration of diuretics, with or without albumin.
      We hypothesize that intravenous 25% albumin plus furosemide, by comparison with
      furosemide alone, improves diuresis, oxygenation, and hemodynamic stability in
      the deresuscitation of critically ill, hypoalbuminemic patients. We propose a
      pilot study to determine the feasibility of a trial to investigate this
      hypothesis. METHODS/DESIGN: FADE is a single-center, parallel, pilot randomized
      controlled trial. We aim to allocate 50 hemodynamically stable, hypoalbuminemic
      adult patients receiving diuresis to treatment with either 100 ml of either 25%
      albumin or normal saline placebo twice daily, for a total of six doses. Diuretics
      are to be prescribed by the caregiving team at least twice daily, and
      administered within 2 hours following study treatment. Patients, intensive care
      unit (ICU) clinicians, data collectors, and outcome adjudicators will be blinded
      to treatment allocation. Feasibility outcome measures include the proportion of
      patients receiving albumin within 2 hours of diuretic, the proportion of patients
      receiving the full six doses of study treatment, the proportion of patients who
      receive open label 25% albumin, and the rate of recruitment. Physiologic,
      laboratory, and clinical data are collected until discharge from the ICU or until
      30 days. DISCUSSION: This is the first randomized trial to assess the use of
      hyperoncotic albumin in addition to diuretics in a general ICU population. Should
      this pilot study demonstrate feasibility, the primary outcome measure of the
      larger clinical trial will be the number of ventilator-free days, with secondary
      clinical outcome measures of duration of mechanical ventilation, length of ICU
      stay, episodes of hemodynamic instability and mortality. The addition of 25%
      albumin to standard diuretic therapy is a promising treatment in the post
      resuscitation care of the critically ill patient. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02055872; ISRCTN70191881.

PMID- 24919685
TI  - Multi-dimensional electron microscopy.

PMID- 24919686
TI  - Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates
      diabetes-induced renal damage through the advanced glycation end product-related
      pathway in db/db mice.
AB  - This study was conducted to examine whether oligonol, a low-molecular-weight
      polyphenol derived from lychee fruit, has an ameliorative effect on diabetes
      induced alterations, such as advanced glycation end product (AGE) formation or
      apoptosis in the kidneys of db/db mice with type 2 diabetes. Oligonol [10 or 20
      mg/(kg body weight . d), orally] was administered every day for 8 wk to
      prediabetic db/db mice, and its effect was compared with vehicle-treated db/db
      and normal control mice (m/m). The administration of oligonol decreased the
      elevated renal glucose concentrations and reactive oxygen species in db/db mice
      (P < 0.05). The increased serum urea nitrogen and creatinine concentrations,
      which reflect renal dysfunction in db/db mice, were substantially lowered by
      oligonol. Oligonol reduced renal protein expression of NAD(P)H oxidase subunits
      (p22 phagocytic oxidase and NAD(P)H oxidase-4), AGEs (except for pentosidine),
      and c-Jun N-terminal kinase B-targeting proinflammatory tumor necrosis factor
      alpha (P < 0.05). Oligonol improved the expressions of antiapoptotic [B-cell
      lymphoma protein 2 (Bcl-2) and survivin] and proapoptotic [Bcl-2-associated X
      protein, cytochrome c, and caspase-3] proteins in the kidneys of db/db mice (P <
      0.05). In conclusion, these results provide important evidence that oligonol
      exhibits a pleiotropic effect on AGE formation and apoptosis-related variables,
      representing renoprotective effects against the development of diabetic
      complications in db/db mice with type 2 diabetes. 

PMID- 24919687
TI  - Functional characterization of the duck and turkey fatty acyl elongase enzymes
      ELOVL5 and ELOVL2.
AB  - In most Western countries, the consumption of fish is low and insufficient to
      provide the recommended daily intake of the n-3 (omega-3) long-chain
      polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5n-3) and
      docosahexaenoic acid (DHA; 22:6n-3). Poultry has the potential to be a
      sustainable source of EPA and DHA if poultry species are capable of synthesizing
      these n-3 PUFAs from dietary plant-derived alpha-linolenic acid (ALA; 18:3n-3).
      In most animals, the elongation of very long-chain fatty acids (ELOVL) enzyme
      ELOVL2 is essential for conversion of dietary ALA to DHA because only ELOVL2 and
      not ELOVL5 can elongate docosapentaenoic acid (DPA; 22:5n-3) to 24:5n-3, the
      precursor of DHA. The chicken is the only poultry species in which elongase
      enzymes have been functionally characterized, and chicken ELOVL5 had unique DPA
      to-24:5n-3 activity, which may enable chickens to synthesize more DHA than other
      animals. By using a yeast expression system, we examined the duck and turkey
      elongases, ELOVL2 and ELOVL5, to understand if all poultry species have similar
      potential to synthesize EPA and DHA. The duck and turkey ELOVL5 enzymes were
      active with C18-20 PUFAs only. The duck ELOVL2 had a broad substrate specificity
      with C18-22 PUFAs, whereas the turkey ELOVL2 was active only with EPA and C22
      PUFAs. Both duck and turkey ELOVL2 enzymes catalyzed 2 rounds of EPA elongation,
      with the products being DPA and its elongation product, 24:5n-3. With exogenous
      DPA, both duck and turkey ELOVL2 synthesized 24:5n-3, with the duck ELOVL2 being
      more active than the turkey ELOVL2. The reason for the lack of DPA elongation
      activity by the duck and turkey ELOVL5 enzymes compared with the chicken ELOVL5
      could not be elucidated by protein sequence comparisons. By using the elongase
      enzyme activities only as a predictor of DHA synthesis, ducks may have a similar
      ability to chickens to convert increasing dietary ALA to DHA. 

PMID- 24919688
TI  - The interplay of gender, mood, and stress hormones in the association between
      emotional eating and dietary behavior.

PMID- 24919690
TI  - Intestinal and systemic inflammatory responses are positively associated with
      sulfidogenic bacteria abundance in high-fat-fed male C57BL/6J mice.
AB  - Recent studies have highlighted the relation between high-fat (HF) diets, the gut
      microbiota, and inflammation. However, the role of sulfidogenic bacteria in
      mediating these effects has been explored only recently. Therefore, we tested the
      hypothesis that an HF diet rich in saturated fat stimulates sulfidogenic bacteria
      and that these increases correlate with intestinal and systemic inflammatory
      responses. Forty C57BL/6J male mice were fed a low-fat (LF; 10% of energy) or an
      HF lard-based (60% of energy) diet for 6 or 20 wk. Mucosa samples were collected
      from the ileum, cecum, and colon and used for measuring 16S ribosomal RNA and
      functional genes of sulfidogenic bacteria. Matching intestinal samples and
      visceral and subcutaneous white adipose tissue (WAT) depots were used to measure
      mRNA abundance for inflammatory genes. Mice fed the HF diet had greater (P <
      0.05) abundance of 3 types of sulfidogenic bacteria, primarily in colonic mucosa,
      compared with LF-fed mice at week 20. Although HF feeding did not increase
      intestinal inflammation at week 6, ileal markers of macrophage infiltration and
      inflammation were upregulated (P < 0.05) 1- to 6-fold at week 20. HF feeding
      impaired the localization of the tight junction protein zonula occludens 1 at the
      apical area of the ileal epithelium at weeks 6 and 20. Mice fed the HF diet had 1
      to 100-fold greater (P < 0.05) mRNA levels of markers of macrophage infiltration
      in visceral and subcutaneous WAT at week 20, but not at week 6, compared with LF
      fed mice. These results provide evidence that chronic, but not acute, consumption
      of an HF lard-based diet may be linked with pathways of microbial metabolism that
      potentially contribute to chronic intestinal and systemic inflammation. Such
      linkage provides further support for reducing consumption of saturated fats. 

PMID- 24919689
TI  - Shifts in the recent distribution of energy intake among U.S. children aged 2-18
      years reflect potential abatement of earlier declining trends.
AB  - Recent national surveys suggest that child obesity in the United States may have
      reached a plateau, but corresponding trends in energy intake have not been
      examined in depth. This article evaluates medium-term trends in children's
      reported energy intake by using 4 waves of national dietary surveillance from
      2003-2004 to 2009-2010. The analysis uses up to 2 24-h dietary recalls,
      incorporating methods that address challenges in estimating usual intake,
      accounting for intraindividual variance and covariates such as the presence of
      atypical consumption days. Quantile regression was used to assess disparities in
      intake among sociodemographic subgroups at extremes of the distribution as well
      as at the median, and the potential influence of misreporting was evaluated.
      Results indicated that after an initial decline in intakes across all age groups
      through 2007-2008, there were significant increases of ~90 kcal/d at the median
      among adolescents in 2009-2010, whereas intakes in younger children remained
      steady. Among adolescent boys, the recent increase was larger at the 90th
      percentile than at the median. Intake trends did not vary by race/ethnic group,
      among whom intakes were similar at the upper end of the distribution.
      Misreporting did not influence trends over time, but intakes were lower in
      younger children and higher in older children after excluding misreporters.
      Overall, findings suggest that declines in children's energy intake from 2003
      2004 through 2007-2008 were consistent with the obesity plateau observed in most
      age and gender subgroups through 2009-2010. However, there is evidence of
      increased intakes among adolescents in 2009-2010, which may threaten the earlier
      abatement in overweight in this older age group. 

PMID- 24919691
TI  - Human milk oligosaccharides differ between HIV-infected and HIV-uninfected
      mothers and are related to necrotizing enterocolitis incidence in their preterm
      very-low-birth-weight infants.
AB  - The heavy burden of maternal HIV infection has resulted in a high prevalence of
      premature birth and associated necrotizing enterocolitis (NEC). Human milk
      oligosaccharides (HMOs) were recently associated with HIV infection and
      transmission through breastfeeding and were also shown to reduce NEC in an animal
      model, particularly the HMO disialyllacto-N-tetraose (DSLNT). The primary aim of
      this study was to verify differences in HMO composition between HIV-infected and
      HIV-uninfected women. The secondary aim was to assess whether the HMO composition
      in the milk of mothers whose infants were diagnosed with NEC differs from that of
      mothers whose infants did not develop NEC. This study forms part of a larger
      clinical trial conducted at the Tygerberg Children's Hospital, Cape Town, South
      Africa, which recruited HIV-infected and HIV-uninfected mothers and their preterm
      infants (<34 wk gestation; >=500 and <=1250 g). Eighty-two mother-infant pairs
      were selected for the substudy. Mother-infant pairs were stratified according to
      the mother's HIV (infected/uninfected) and secretor status
      (secretor/nonsecretor). HMOs in 4- and 28-d postpartum milk samples were analyzed
      by HPLC and compared between groups. Our results confirm previous reports that
      HIV-infected mothers have higher relative abundances of 3'-sialyllactose in their
      milk compared with HIV-uninfected mothers (10.7% vs. 6.8%; P < 0.01). Most
      intriguingly, the data also indicated that low concentrations of DSLNT in the 4-d
      milk samples in the mother's milk increased the infant's risk of NEC (200 +/- 126
      vs. 345 +/- 186 MUg/mL; P < 0.05), which is in accordance with results from
      previously published animal studies and warrants further investigation. This
      trial was registered at clinicaltrials.gov as NCT01868737. 

PMID- 24919692
TI  - Skeletal muscle disuse atrophy is not attenuated by dietary protein
      supplementation in healthy older men.
AB  - Short successive periods of muscle disuse, due to injury or illness, can
      contribute significantly to the loss of muscle mass with aging (sarcopenia). It
      has been suggested that increasing the protein content of the diet may be an
      effective dietary strategy to attenuate muscle disuse atrophy. We hypothesized
      that protein supplementation twice daily would preserve muscle mass during a
      short period of limb immobilization. Twenty-three healthy older (69 +/- 1 y) men
      were subjected to 5 d of one-legged knee immobilization by means of a full-leg
      cast with (PRO group; n = 11) or without (CON group; n = 12) administration of a
      dietary protein supplement (20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g
      of fat) twice daily. Two d prior to and immediately after the immobilization
      period, single-slice computed tomography scans of the quadriceps and single-leg 1
      repetition maximum strength tests were performed to assess muscle cross-sectional
      area (CSA) and leg muscle strength, respectively. Additionally, muscle biopsies
      were collected to assess muscle fiber characteristics as well as mRNA and protein
      expression of selected genes. Immobilization decreased quadriceps' CSAs by 1.5 +/
      0.7% (P < 0.05) and 2.0 +/- 0.6% (P < 0.05), and muscle strength by 8.3 +/- 3.3%
      (P < 0.05) and 9.3 +/- 1.6% (P < 0.05) in the CON and PRO groups, respectively,
      without differences between groups. Skeletal muscle myostatin, myogenin, and
      muscle RING-finger protein-1 (MuRF1) mRNA expression increased following
      immobilization in both groups (P < 0.05), whereas muscle atrophy F-box/atrogen-1
      (MAFBx) mRNA expression increased in the PRO group only (P < 0.05). In
      conclusion, dietary protein supplementation (~20 g twice daily) does not
      attenuate muscle loss during short-term muscle disuse in healthy older men. This
      trial was registered at clinicaltrials.gov as NCT01588808. 

PMID- 24919693
TI  - Cross-national comparisons of sickness absence systems and statistics: towards
      common indicators.
AB  - We aimed to identify common elements in work sickness absence (SA) in Spain,
      Sweden and The Netherlands. We estimated basic statistics on benefits
      eligibility, SA incidence and duration and distribution by major diagnostics. The
      three countries offer SA benefits for at least 12 months and wage replacement,
      differing in who and when the payer assumes responsibility; the national health
      systems provide health care with participation from occupational health services.
      Episodes per 1000 salaried workers and episode duration varied by country; their
      distribution by diagnostic was similar. Basic and useful SA indicators can be
      constructed to facilitate cross-country comparisons. 

PMID- 24919694
TI  - Can media images of obese people undermine health messages? An experimental study
      of visual representation and risk perception.
AB  - BACKGROUND: Images depicting morbidly obese models [i.e. body mass index (BMI)
      >40] often accompany media articles about the health risks of being overweight
      (i.e. BMI 25-30). Little is known about the effect of this mismatch on people's
      understanding of risk, and perceptions of message relevance. METHODS: In total,
      563 participants (291 overweight/obese and 272 healthy weight) were randomly
      allocated to read a health message about the risk of heart disease posed by being
      overweight, presented alongside (i) a photo of an overweight model, (ii) a
      morbidly obese model or (iii) no photo. Between-group differences in the primary
      outcomes of message relevance, and the body size perceived to be 'at risk', were
      assessed, and the potential moderating effects of motivation, weight concern and
      existing risk knowledge explored. RESULTS: Overweight and obese participants in
      the exaggerated (morbidly obese) image condition interpreted health risks to
      relate to a larger body size than those who saw no image (F(2, 290) = 4.06, P =
      0.02). There was no experimental effect on perceived personal relevance (F(2,
      290) = 0.25, P = 0.38). No significant moderation effects were detected, and
      there was no effect of study condition in healthy weight participants for either
      outcome. CONCLUSION: The findings suggest that the use of morbidly obese models
      in messages regarding the health risks of being overweight may undermine the
      impact of these messages among those who they most aim to reach; the reader may
      perceive a reduced risk of being 'only' overweight, and that a higher weight is
      needed for the negative effects of excess weight to occur.

PMID- 24919695
TI  - Excess winter deaths in Europe: a multi-country descriptive analysis.
AB  - BACKGROUND: Winter deaths are a known health and social care challenge for many
      countries. A previous international comparison showed significant differences in
      excess winter deaths across Europe in the 1990s, with the northern countries
      having lower excess winter mortality than those in southern Europe. METHODS: The
      Excess Winter Deaths Index (EWDI) is the ratio of deaths in the winter period
      (December to March) compared with deaths in the non-winter period. Data from the
      Eurostat database and national registries were used to calculate the EWDI for 31
      countries in Europe across the time period 2002/2003 to 2010/2011. RESULTS:
      National EWDI values show heterogeneity, with a broad pattern of increasing EWDI
      values from northern to southern Europe and increasing mean winter temperature
      (r(2) = 0.50, P > 0.0001). Malta, Portugal, Spain, Cyprus and Belgium all had an
      EWDI that was statistically significantly higher than the average EWDI for the
      other 30 European countries. There was no clear association between country-level
      EWDI and the level of inter-annual variability in winter temperature across
      Europe. DISCUSSION: This article demonstrates the differences in EWDI that exist
      between European countries with implications for both research and policy. Many
      deaths may be avoidable as environmental, social and personal factors are known
      to contribute to winter mortality. We now need to work to better understand the
      causes of inter-country differences.

PMID- 24919696
TI  - Standard and trace-dose lithium: a systematic review of dementia prevention and
      other behavioral benefits.
AB  - OBJECTIVE: Dementia is a major public health issue, with notably high rates in
      persons with mood illnesses. Lithium has been shown to have considerable
      neuroprotective effects, even in trace or low doses. The aim of this review is to
      summarize the current understanding of lithium benefits in trace or low doses in
      dementia prevention and for other behavioral or medical benefits. METHODS: A
      systematic review identified 24 clinical, epidemiological, and biological reports
      that met inclusion criteria of assessing lithium in standard or low doses for
      dementia or other behavioral or medical benefits. RESULTS: Five out of seven
      epidemiological studies found an association between standard-dose lithium and
      low dementia rates. Nine out of 11 epidemiological studies, usually of drinking
      water sources, found an association between trace-dose lithium and low
      suicide/homicide/mortality and crime rates. All four small randomized clinical
      trials of lithium for Alzheimer's dementia have found at least some clinical or
      biological benefits versus placebo. Only one small randomized clinical trial
      (RCT) of trace lithium has been conducted, assessing mood symptoms in former
      substance abusers, and found benefit with lithium versus placebo. CONCLUSIONS:
      Lithium, in both standard and trace doses, appears to have biological benefits
      for dementia, suicide, and other behavioral outcomes. Further RCT research of
      trace lithium in dementia is warranted.

PMID- 24919697
TI  - Surface modification of SU-8 for enhanced cell attachment and proliferation
      within microfluidic chips.
AB  - Advances in micro-electro-mechanical systems (MEMS) have led to an increased
      fabrication of micro-channels. Microfabrication techniques are utilized to
      develop microfluidic channels for continuous nutrition supply to cells inside a
      micro-environment. The ability of cells to build tissues and maintain tissue
      specific functions depends on the interaction between cells and the extracellular
      matrix (ECM). SU-8 is a popular photosensitive epoxy-based polymer in MEMS. The
      patterning of bare SU-8 alone does not provide the appropriate ECM necessary to
      develop microsystems for biological applications. Manipulating the chemical
      composition of SU-8 will enhance the biological compatibility, giving the
      fabricated constructs the appropriate ECM needed to promote a functional tissue
      array. This article investigates three frequently used surface treatment
      techniques: (1) plasma treatment, (2) chemical reaction, and (3) deposition
      treatment to determine which surface treatment is the most beneficial for
      enhancing the biological properties of SU-8. The investigations presented in this
      article demonstrated that the plasma, gelatin, and sulfuric acid treatments have
      a potential to enhance SU-8's surface for biological application. Of course each
      treatment has their advantages and disadvantages (application dependent). Cell
      proliferation was studied with the use of the dye Almar Blue, and a micro-plate
      reader. After 14 days, cell proliferation to plasma treated surfaces was
      statistically significantly enhanced (p < 0.00001), compared to untreated
      surfaces. The plasma treated surface is suggested to be the better of the three
      treatments for biological enhancement followed by gelatin and sulfuric acid
      treatments, respectively.

PMID- 24919698
TI  - Chiral organoborane Lewis pairs derived from pyridylferrocene.
AB  - In an effort to develop a new class of redox-active chiral Lewis pairs, pyridine
      and borane moieties with different steric and electronic properties were
      introduced onto a planar chiral 1,2-disubstituted ferrocene framework. Metathesis
      of lithiated, stannylated, or mercuriated pyridylferrocenes with boron halides
      afforded (pR)-2-[bis(pentafluorophenyl)boryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene
      (4-Pf), (pR)-2-[dimesitylboryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Mes), (pS)
      2-(bis(pentafluorophenyl)boryl)-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Pf),
      or (pS)-2-[dimesitylboryl]-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Mes). The
      borylated products were analyzed by multinuclear NMR spectroscopy, HRMS, and
      single-crystal X-ray diffraction. Chiral HPLC and optical-rotation measurements
      were employed to assess the stereoselectivity of the borylation process and to
      establish the correct stereochemical assignments. The strength of the B-N
      interactions were investigated in solution and in the solid state. Compounds 4-Pf
      and 4-Mes formed robust 'closed' B-N heterocyclic systems that proved to be
      perfectly stable to air and moisture, whereas 5-Pf established a dynamic
      equilibrium, in which the B-N heterocycle was observed exclusively at room
      temperature, but opened up at high temperature according to (19)F NMR exchange
      spectroscopy data. As a consequence, 5-Pf reacted readily with a molecule of
      water to generate a ring-opened pyridinium borate. The combination of bulky
      borane and bulky pyridyl groups in 5-Mes led to a completely 'open' frustrated
      Lewis pair system with uncomplexed pyridine and borane groups, even at room
      temperature. Electrochemical studies were performed and the effect of preparative
      ferrocene oxidation on the structural features was also explored.

PMID- 24919699
TI  - K-Pg events facilitated lineage transitions between terrestrial and aquatic
      ecosystems.
AB  - We use dated phylogenetic trees for tetrapod vertebrates to identify lineages
      that shifted between terrestrial and aquatic ecosystems in terms of feeding or
      development, and to assess the timing of such events. Both stem and crown lineage
      ages indicate a peak in transition events in correspondence with the K-Pg mass
      extinction. This meets the prediction that changes in competitive pressure and
      resource availability following mass extinction events should facilitate such
      transitions. 

PMID- 24919700
TI  - Sex ratio influences the motivational salience of facial attractiveness.
AB  - The sex ratio of the local population influences mating-related behaviours in
      many species. Recent experiments show that male-biased sex ratios increase the
      amount of financial resources men will invest in potential mates, suggesting that
      sex ratios influence allocation of mating effort in humans. To investigate this
      issue further, we tested for effects of cues to the sex ratio of the local
      population on the motivational salience of attractiveness in own-sex and opposite
      sex faces. We did this using an effort-based key-press task, in which the
      motivational salience of facial attractiveness was assessed in samples of faces
      in which the ratio of male to female images was manipulated. The motivational
      salience of attractive opposite-sex, but not own-sex, faces was greater in the
      own-sex-biased (high competition for mates) than in the opposite-sex-biased (low
      competition for mates) condition. Moreover, this effect was not modulated by
      participant sex. These results present new evidence that sex ratio influences
      human mating-related behaviours. They also present the first evidence that the
      perceived sex ratio of the local population may modulate allocation of mating
      effort in women, as well as men. 

PMID- 24919701
TI  - Cardiac myoglobin deficit has evolved repeatedly in teleost fishes.
AB  - Myoglobin (Mb) is the classic vertebrate oxygen-binding protein present in
      aerobic striated muscles. It functions principally in oxygen delivery and
      provides muscle with its characteristic red colour. Members of the Antarctic
      icefish family (Channichthyidae) are widely thought to be extraordinary for
      lacking cardiac Mb expression, a fact that has been attributed to their low
      metabolic rate and unusual evolutionary history. Here, we report that cardiac Mb
      deficit, associated with pale heart colour, has evolved repeatedly during teleost
      evolution. This trait affects both gill- and air-breathing species from temperate
      to tropical habitats across a full range of salinities. Cardiac Mb deficit
      results from total pseudogenization in three-spined stickleback and is associated
      with a massive reduction in mRNA level in two species that evidently retain
      functional Mb. The results suggest that near or complete absence of Mb-assisted
      oxygen delivery to heart muscle is a common facet of teleost biodiversity, even
      affecting lineages with notable oxygen demands. We suggest that Mb deficit may
      affect how different teleost species deal with increased tissue oxygen demands
      arising under climate change. 

PMID- 24919702
TI  - The body-size dependence of mutual interference.
AB  - The parameters that drive population dynamics typically show a relationship with
      body size. By contrast, there is no theoretical or empirical support for a body
      size dependence of mutual interference, which links foraging rates to consumer
      density. Here, I develop a model to predict that interference may be positively
      or negatively related to body size depending on how resource body size scales
      with consumer body size. Over a wide range of body sizes, however, the model
      predicts that interference will be body-size independent. This prediction was
      supported by a new dataset on interference and consumer body size. The
      stabilizing effect of intermediate interference therefore appears to be roughly
      constant across size, while the effect of body size on population dynamics is
      mediated through other parameters. 

PMID- 24919703
TI  - The interactive effects of competition and predation risk on dispersal in an
      insect.
AB  - Dispersal dynamics have significant consequences for ecological and evolutionary
      processes. Previous work has demonstrated that dispersal can be context
      dependent. However, factors affecting dispersal are typically considered in
      isolation, despite the probability that individuals make dispersal decisions in
      response to multiple, possibly interacting factors. We examined whether two
      ecological factors, predation risk and intraspecific competition, have
      interactive effects on dispersal dynamics. We performed a factorial experiment in
      mesocosms using backswimmers (Notonecta undulata), flight-capable, semi-aquatic
      insects. Emigration rates increased with density, and increased with predation
      risk at intermediate densities; however, predation had minimal effects on
      emigration at high and low densities. Our results indicate that factorial
      experiments may be required to understand dispersal dynamics under realistic
      ecological conditions. 

PMID- 24919704
TI  - Rapid evolution of mimicry following local model extinction.
AB  - Batesian mimicry evolves when individuals of a palatable species gain the
      selective advantage of reduced predation because they resemble a toxic species
      that predators avoid. Here, we evaluated whether-and in which direction-Batesian
      mimicry has evolved in a natural population of mimics following extirpation of
      their model. We specifically asked whether the precision of coral snake mimicry
      has evolved among kingsnakes from a region where coral snakes recently (1960)
      went locally extinct. We found that these kingsnakes have evolved more precise
      mimicry; by contrast, no such change occurred in a sympatric non-mimetic species
      or in conspecifics from a region where coral snakes remain abundant. Presumably,
      more precise mimicry has continued to evolve after model extirpation, because
      relatively few predator generations have passed, and the fitness costs incurred
      by predators that mistook a deadly coral snake for a kingsnake were historically
      much greater than those incurred by predators that mistook a kingsnake for a
      coral snake. Indeed, these results are consistent with prior theoretical and
      empirical studies, which revealed that only the most precise mimics are favoured
      as their model becomes increasingly rare. Thus, highly noxious models can
      generate an 'evolutionary momentum' that drives the further evolution of more
      precise mimicry-even after models go extinct. 

PMID- 24919705
TI  - Team swimming in ant spermatozoa.
AB  - In species where females mate promiscuously, competition between ejaculates from
      different males to fertilize the ova is an important selective force shaping many
      aspects of male reproductive traits, such as sperm number, sperm length and sperm
      sperm interactions. In eusocial Hymenoptera (bees, wasps and ants), males die
      shortly after mating and their reproductive success is ultimately limited by the
      amount of sperm stored in the queen's spermatheca. Multiple mating by queens is
      expected to impose intense selective pressure on males to optimize the transfer
      of sperm to the storage organ. Here, we report a remarkable case of cooperation
      between spermatozoa in the desert ant Cataglyphis savignyi. Males ejaculate
      bundles of 50-100 spermatozoa. Sperm bundles swim on average 51% faster than
      solitary sperm cells. Team swimming is expected to increase the amount of sperm
      stored in the queen spermatheca and, ultimately, enhance male posthumous fitness.

PMID- 24919706
TI  - Design, synthesis and excited-state properties of mononuclear Ru(II) complexes of
      tridentate heterocyclic ligands.
AB  - Artificial photosynthetic systems that contain light-harvesting coordination
      complexes may one day replace conventional non-renewable sources of energy with
      renewable solar energy sources. Light-Harvesting Complexes (LHC) are important
      components of natural photosynthetic systems and are also sought after in
      artificial systems as well. Polynuclear photoactive complexes are therefore very
      attractive, and those based on stereogenic [Ru(2,2'-bipyridine)3](2+) are
      photophysically appealing, but difficult to obtain in a stereochemically pure
      form. On the other hand, polynuclear complexes based on the achiral
      [Ru(2,2':6',2''-terpyridine)2](2+) motif are easy to synthesise, however, these
      complexes are devoid of attractive excited-state properties. Hence strategies to
      increase the r.t. excited-state lifetime of these complexes would be of practical
      importance in vectorial electron and/or electron transfer in various
      optoelectronic applications. This tutorial review will report on the
      sophisticated synthetic strategies currently in use to enhance the photophysical
      properties of mononuclear Ru(II) complexes of tridentate ligands at room
      temperature.

PMID- 24919707
TI  - Review of plants and their constituents in the therapy of cerebral ischemia.
AB  - Cerebral ischemia is a condition in which there is insufficient blood flow to the
      brain to meet metabolic demand. This leads to cerebral hypoxia and thus to the
      death of neuronal cells or stroke. The limited number of medicines currently
      available for patients following ischemic stroke and insufficient data on
      efficiency of these chemicals in the treatment of stroke led us to the search for
      novel therapeutic approaches. Recent studies have focused on the possible
      capacity of natural compounds extracted from vegetables and fruits, to prevent
      human disabilities caused by cerebral ischemia. In this review, we will discuss
      some plants and their constituents that may protect brain ischemia or delay the
      neurological disorders following a stroke. We have reviewed different studies in
      scientific databases that investigate herbal compounds and their effects on
      cerebral ischemia.

PMID- 24919708
TI  - Radiation exposure of patients undergoing whole-body FDG-PET/CT examinations: an
      update pursuant to the new ICRP recommendations.
AB  - AIM: Reinvestigation of the radiation exposure of patients undergoing whole-body
      [18F]FDG-PET/CT examinations pursuant to the revised recommendations of the ICRP.
      METHODS: Conversion coefficients for equivalent organ doses were determined for
      realistic anthropomorphic phantoms of reference persons. Based on these data,
      conversion coefficients for the effective dose were calculated using the revised
      tissue-weighting factors that account for the different radiation
      susceptibilities of organs and tissues, and the redefinition of the group
      'remainder tissues'. RESULTS: Despite the markedly changed values of the
      equivalent organ doses estimated for FDG and of the tissue-weighting factors, the
      conversion coefficient for the effective dose resulting from FDG administration
      decreases only slightly by 10 %. For whole-body CT scans it remains even
      unchanged. CONCLUSION: The updated dose coefficients provide a valuable tool to
      easily assess the generic radiation risk of patients undergoing whole-body PET/CT
      (or PET/MRI) examinations and can be used, amongst others, for protocol
      optimization.

PMID- 24919710
TI  - Dilemmas in undertaking research in paediatric intensive care.
AB  - Providing evidence-based interventions for infants and children is important in
      paediatric intensive care, where decision making impacts most acutely on
      morbidity and mortality. However, despite the major progress of medicine in the
      21st century, we still lack this evidence for majority of the decisions we make.
      In this article, we explore and suggest possible solutions for several dilemmas
      faced by paediatric intensive care researchers. These include ethical dilemmas
      such as validity of informed consent, use of deferred consent, balancing risk
      versus benefit and methodological dilemmas such as how to generate high-quality
      evidence with low-patient volume, choice of valid outcome measures and how best
      to use research and researchers' networks. 

PMID- 24919709
TI  - Interaction specificity and coexpression of rice NPR1 homologs 1 and 3 (NH1 and
      NH3), TGA transcription factors and Negative Regulator of Resistance (NRR)
      proteins.
AB  - BACKGROUND: The nonexpressor of pathogenesis-related genes 1, NPR1 (also known as
      NIM1 and SAI1), is a key regulator of SA-mediated systemic acquired resistance
      (SAR) in Arabidopsis. In rice, the NPR1 homolog 1 (NH1) interacts with TGA
      transcriptional regulators and the Negative Regulator of Resistance (NRR) protein
      to modulate the SAR response. Though five NPR1 homologs (NHs) have been
      identified in rice, only NH1 and NH3 enhance immunity when overexpressed. To
      understand why NH1 and NH3, but not NH2, NH4, or NH5, contribute to the rice
      immune response, we screened TGA transcription factors and NRR-like proteins for
      interactions specific to NH1 and NH3. We also examined their co-expression
      patterns using publicly available microarray data. RESULTS: We tested five NHs,
      four NRR homologs (RHs), and 13 rice TGA proteins for pair-wise protein
      interactions using yeast two-hybrid (Y2H) and split YFP assays. A survey of 331
      inter-family interactions revealed a broad, complex protein interaction network.
      To investigate preferred interaction partners when all three families of proteins
      were present, we performed a bridged split YFP assay employing YFPN-fused TGA,
      YFPC-fused RH, and NH proteins without YFP fusions. We found 64 tertiary
      interactions mediated by NH family members among the 120 sets we examined. In the
      yeast two-hybrid assay, each NH protein was capable of interacting with most TGA
      and RH proteins. In the split YFP assay, NH1 was the most prevalent interactor of
      TGA and RH proteins, NH3 ranked the second, and NH4 ranked the third. Based on
      their interaction with TGA proteins, NH proteins can be divided into two
      subfamilies: NH1, NH2, and NH3 in one family and NH4 and NH5 in the other.In
      addition to evidence of overlap in interaction partners, co-expression analyses
      of microarray data suggest a correlation between NH1 and NH3 expression patterns,
      supporting their common role in rice immunity. However, NH3 is very tightly co
      expressed with RH1 and RH2, while NH1 is strongly, inversely co-expressed with RH
      proteins, representing a difference between NH1 and NH3 expression patterns.
      CONCLUSIONS: Our genome-wide surveys reveal that each rice NH protein can partner
      with many rice TGA and RH proteins and that each NH protein prefers specific
      interaction partners. NH1 and NH3 are capable of interacting strongly with most
      rice TGA and RH proteins, whereas NH2, NH4, and NH5 have weaker, limited
      interaction with TGA and RH proteins in rice cells. We have identified rTGA2.1,
      rTGA2.2, rTGA2.3, rLG2, TGAL2 and TGAL4 proteins as the preferred partners of NH1
      and NH3, but not NH2, NH4, or NH5. These TGA proteins may play an important role
      in NH1- and NH3-mediated immune responses. In contrast, NH4 and NH5
      preferentially interact with TGAL5, TGAL7, TGAL8 and TGAL9, which are predicted
      to be involved in plant development.

PMID- 24919711
TI  - Brain injury: younger is not better.

PMID- 24919712
TI  - The incidence and presentation of neonatal herpes in a single UK tertiary centre,
      2006-2013.
AB  - BACKGROUND: Neonatal herpes infection can have devastating outcomes for otherwise
      healthy babies. In the UK, the stated incidence is low at 1.65 per 100 000 live
      births, which is in contrast with an incidence of 33 per 100 000 in the USA. We
      aimed to discover the current incidence of neonatal herpes infection in our
      tertiary service, determine the timing of presentations, and to consider which
      presenting features could be used for early recognition and prognostication.
      METHODS: All cases of neonatal herpes infection occurring in the last 8 years
      were reviewed, and those cases from an agreed population were used to calculate
      an incidence. The statistical associations between clinical features and death
      were examined. FINDINGS: There were 57 291 live births between 2006 and 2012.
      Nineteen cases were identified including 10 from the study population (17.5/100
      000 live births). There were nine deaths, all presenting later than 6 days of
      age. Independent predictors of death were haemodynamic instability, coagulopathy,
      bleeding and central nervous system features at presentation. All presentations
      occurred within 2 weeks of birth and were varied and often non-specific.
      INTERPRETATION: Our incidence rate of 17.5 per 100 000 live births represents a
      significant increase and is much more in line with the higher incidence rates
      seen in the USA. The range of presentations shows the non-specific nature of this
      disease. We advocate a heightened awareness of this treatable disease in the UK,
      and encourage adoption of modern rapid diagnostic techniques and the wider
      inclusion of Aciclovir in treatment regimens for neonatal sepsis.

PMID- 24919713
TI  - A771726, an anti-inflammatory drug, exerts an anticancer effect and reverses
      tamoxifen resistance in endocrine-resistant breast cancer cells.
AB  - A771726, an orally available anti-inflammatory agent, has been approved for the
      treatment of multiple sclerosis by diminishing entire inflammatory responses
      through multiple signaling pathways. Recently, a few emerging studies have
      focused on the potential application of A771726 in cancer therapy, less on the
      treatment of breast cancer and particularly on overcoming drug resistance in
      breast cancer. We report here for the first time the cytotoxic activity and drug
      resistance reversal of A771726 in acquired tamoxifen-resistant breast cancer cell
      line MCF-7/LCC9. We discovered that A771726 treatment showed antiproliferative
      activities in MCF-7/LCC9 cells, which were even more sensitive to A771726 than
      their parental tamoxifen-sensitive cells (MCF-7). A771726 also exerted pro
      apoptotic activities and induced cell cycle arrest at the G1 phase. Notably,
      treatment of A771726 restored the sensitivity of MCF-7/LCC9 cells to tamoxifen.
      Western blot analysis revealed that A771726 decreased the phosphorylation level
      of Src, one key driver of tamoxifen resistance. Moreover, in order to
      comprehensively clarify the mechanisms of A771726 in anti-estrogen-resistant
      cells, we explored a genome-wide transcriptomic analysis, and showed that A771726
      could modulate multiple signaling pathways (e.g. cell cycle, apoptosis, MAPK,
      metabolism and p53 signaling pathway) and cellular processes (e.g. signal
      transduction, transcription and cell cycle). Overall, our results indicate that
      A771726 alone and the combination of A771726 with anti-estrogens may be of
      therapeutic benefit for ER-positive and endocrine-resistant breast cancer.

PMID- 24919714
TI  - Transplanted hUCB-MSCs migrated to the damaged area by SDF-1/CXCR4 signaling to
      promote functional recovery after traumatic brain injury in rats.
AB  - Transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) have
      exhibited considerable therapeutic potential for traumatic brain injury (TBI).
      However, how hUC-MSCs migrating to the injury region and the mechanism of hUC
      MSCs promoting functional recovery after TBI are still unclear. In this study, we
      investigated whether stromal cell-derived factor-1 (SDF-1) was involved in the
      hUC-MSCs migration and the possible mechanisms that might be involved in the
      beneficial effect on functional recovery. In vitro experiments demonstrated that
      SDF-1 induces a concentration-dependent migration of hUC-MSCs. Furthermore, pre
      treatment with the CXCR4-specific antagonist AMD3100 significantly prevented the
      migration of hUC-MSCs in vitro. We found that the expression of SDF-1 increased
      significantly around the damaged area. Transplanted hUC-MSCs were localized to
      regions where SDF-1 was highly expressed. Additionally, our results showed that
      hUC-MSCs-treated animals showed significantly improved functional recovery
      compared with controls. In hUC-MSCs-transplanted group, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were decreased
      and BrdU-positive cells were significantly increased compared with control group,
      more of BrdU-positive cells co-localized with GFAP. These suggest that SDF-1
      plays an important role in the migration of hUC-MSCs to the damaged area and hUC
      MSCs are beneficial for functional recovery after TBI. 

PMID- 24919715
TI  - Descriptive review: hormonal influences on risk for eating disorder symptoms
      during puberty and adolescence.
AB  - OBJECTIVE: Puberty is an important period of risk for the onset of eating
      pathology in adolescent females. This review focuses on changes in reproductive
      hormones during puberty as one specific psychopathogenic mechanism. METHOD:
      Studies of puberty and eating disorder-related phenotypes were identified using
      search databases and the reference sections of previous literature. RESULTS:
      Correlational studies of adult women and experimental studies of animals provide
      evidence for the effects of reproductive hormones on eating disorder symptoms.
      Very few studies of puberty, however, have directly measured or tested the
      effects of hormonal change in samples of human adolescents. Commonly used
      measures of pubertal development, such as menarche or self-reported pubertal
      status, are relatively poor indicators of individual differences in hormones. The
      extent to which puberty-related hormonal change accounts for elevated risk for
      disordered eating remains unclear. DISCUSSION: Future research is necessary to
      elucidate the specific relations between hormonal change during puberty and risk
      for disordered eating. In particular, there is a need for longitudinal studies
      with multivariate measurement of pubertal development, including direct measures
      of change in reproductive hormones.

PMID- 24919716
TI  - Multiple skin-colored papules with diffuse sclerosis.

PMID- 24919718
TI  - Determination of moulds and mycotoxins in dry dog and cat food using liquid
      chromatography with mass spectrometry and fluorescence detection.
AB  - In this study moulds and 12 mycotoxins in dry pet food samples (25 for dogs and
      24 for cats) were determined. Primary moulds identified were Aspergillus, Mucor
      and Penicillium, found in 55% of the samples. Deoxynivalenol and zearalenone
      (ZEN) were detected in all samples with mean respective concentrations being 97.3
      and 38.3 ug kg(-1) in cat food and 114 and 20.1 ug kg(-1) in dog food. T-2 and HT
      2 toxins were present in 88% and 84% of the samples, respectively. Two samples
      contained fumonisins, with a maximum concentration of 108 ug kg(-1). Aflatoxin B1
      and ochratoxin A were detected in 8% and 45% of the samples, respectively. The
      measured mould and mycotoxin levels were consistent with results obtained by
      other studies. However, potential exposure to relatively high concentrations of
      an oestrogen mycotoxin as is ZEN, especially when in combination with other
      mycotoxins, needs attention. 

PMID- 24919717
TI  - Protective effects of vitamins (C and E) and melatonin co-administration on
      hematological and hepatic functions and oxidative stress in alloxan-induced
      diabetic rats.
AB  - The present study aimed to investigate the potential effects of vitamins (C and
      E)/melatonin co-administration on the hematologic and hepatic functions and
      oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection
      of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood
      glucose levels (hyperglycemia) associated with serious hematologic disorders (P <
      0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (
      18%), hematocrit (Ht) (-18%), hemoglobin content (Hb) (-36%), mean corpuscular
      hemoglobin (MCH) (-17%), and mean corpuscular hemoglobin concentration (MCHC) (
      16%). The activities of aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of
      total cholesterol and triglyceride contents of diabetic rats were, however, noted
      to undergo significant increases by 42% (P < 0.01), 134% (P < 0.001), 27.5% (P <
      0.01), 147% (P < 0.001), and 67% (P < 0.01), respectively, as compared to the
      control animals. Furthermore, a significant increase in malondialdehyde (MDA)
      content and a significant decrease in superoxide dismutase (SOD), catalase (CAT),
      and glutathione peroxidase (GPx) activities were observed in the plasma and
      hepatic tissues of diabetic rats when compared to the controls. Interestingly,
      the treatment with vitamins (C, E) in combination with melatonin was noted to
      reduce the plasma levels of glucose, lower the MDA levels, and restore the
      hematologic parameters and biochemical and antioxidant levels of diabetic rats
      back to normal values, alleviating diabetes metabolic disorders in rats.

PMID- 24919719
TI  - Nutritional interventions for preventing and treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers affect approximately 10% of people in hospitals and
      older people are at highest risk. A correlation between inadequate nutritional
      intake and the development of pressure ulcers has been suggested by several
      studies, but the results have been inconsistent. OBJECTIVES: To evaluate the
      effects of enteral and parenteral nutrition on the prevention and treatment of
      pressure ulcers. SEARCH METHODS: In March 2014, for this first update, we
      searched The Cochrane Wounds Group Specialised Trials Register, the Cochrane
      Central register of Controlled Trials (The Cochrane Library), the Database of
      Abstracts of Reviews of Effects (DARE) (The Cochrane Library), the Health
      Technology Assessment Database (HTA) (The Cochrane Library), the Cochrane
      Methodology Register (The Cochrane Library), NHS Economic Evaluation Database
      (The Cochrane Library), Ovid Medline, Ovid Embase and EBSCO CINAHL. No date,
      language or publication status limits were applied. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) evaluating the effects of enteral or
      parenteral nutrition on the prevention and treatment of pressure ulcers, which
      measured the incidence of new ulcers, ulcer healing or changes in pressure ulcer
      severity. There were no restrictions on types of patient, setting, date,
      publication status or language. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened for inclusion, and disagreement was resolved by
      discussion. Two review authors independently extracted data and assessed quality
      using the Cochrane Collaboration tool for assessing risk of bias. MAIN RESULTS:
      We included 23 RCTs, many were small (between 9 and 4023 participants, median 88)
      and at high risk of bias.Eleven trials compared a combination of nutritional
      supplements, consisting of a minimum of energy and protein in different dosages,
      for the prevention of pressure ulcers. A meta-analysis of eight trials (6062
      participants) that compared the effects of mixed nutritional supplements with
      standard hospital diet found no clear evidence of an effect of supplementation on
      pressure ulcer development (pooled RR 0.86; 95% CI 0.73 to 1.00; P value 0.05;
      I(2) = 13%, random effects). This outcome is at unclear or high risk of
      bias.Fourteen trials evaluated the effects of nutritional supplements on the
      healing of existing pressure ulcers: seven trials examined mixed nutritional
      supplements, three the effects of proteins, two trials examined zinc, and two
      studies examined ascorbic acid. The included trials were heterogeneous with
      regard to participants, interventions, comparisons and outcomes and meta-analysis
      was not appropriate. There was no clear evidence of an improvement in pressure
      ulcer healing from the nutritional supplements evaluated in any of these
      individual studies. AUTHORS' CONCLUSIONS: There is currently no clear evidence of
      a benefit associated with nutritional interventions for either the prevention or
      treatment of pressure ulcers. Further trials of high methodological quality are
      necessary.

PMID- 24919721
TI  - High production of succinyl isoflavone glycosides by Bacillus licheniformis ZSP01
      resting cells in aqueous miscible organic medium.
AB  - To achieve efficient production of succinyldaidzin and succinylgenistin, resting
      cells of a solvent-stable strain Bacillus licheniformis ZSP01 were used to react
      with pure isoflavones or soybean flour extract in a reaction medium with 10%
      dimethyl sulfoxide. Strikingly, 0.8 mM daidzein, 0.8 mM genistein, 2.0 mM
      daidzin, and 2.0 mM genistin were transformed to succinyl isoflavone glycosides
      in 27 H (yield >90%). The soybean flour extract (6.1%, w/v) contained 0.32 mM
      daidzein, 0.84 mM daidzin, 0.38 mM genistein, and 1.04 mM genistin. Over 95% of
      total isoflavones (daidzein, daidzin, genistein, and genistin) in the soybean
      flour extract were converted to succinyl isoflavone glycosides after 27 H. Strain
      ZSP01 shows both high glycosylation and succinylation activities. These results
      suggest that B. licheniformis ZSP01 could be useful for the efficient production
      of succinyl soybean isoflavone glycosides.

PMID- 24919722
TI  - Do human activities influence survival and orientation abilities of larval fishes
      in the ocean?
AB  - The larval stages of most marine fishes spend days to weeks in the pelagic
      environment, where they must find food and avoid predators in order to survive.
      Some fish only spend part of their life history in the pelagic environment before
      returning to their adult habitat, for example, a coral reef. The sensory systems
      of larval fish develop rapidly during the first few days of their lives, and here
      we concentrate on the various sensory cues the fish have available to them for
      survival in the pelagic environment. We focus on the larvae of reef fishes
      because most is known about them. We also review the major threats caused by
      human activities that have been identified to have worldwide impact and evaluate
      how these threats may impact larval-fish survival and orientation abilities. Many
      human activities negatively affect larval-fish sensory systems or the cues the
      fish need to detect. Ultimately, this could lead to decreased numbers of larvae
      surviving to settlement, and, therefore, to decreased abundance of adult fishes.
      Although we focus on species wherein the larvae and adults occupy different
      habitats (pelagic and demersal, respectively), it is important to acknowledge
      that the potential anthropogenic effects we identify may also apply to larvae of
      species like tuna and herring, where both larvae and adults are pelagic. 

PMID- 24919720
TI  - Yoga in addition to standard care for patients with haematological malignancies.
AB  - BACKGROUND: Haematological malignancies are malignant neoplasms of the myeloid or
      lymphatic cell lines including leukaemia, lymphoma and myeloma. In order to
      manage physical and psychological aspects of the disease and its treatment,
      complementary therapies like yoga are coming increasingly into focus. However,
      the effectiveness of yoga practice for people suffering from haematological
      malignancies remains unclear. OBJECTIVES: To assess the effects of yoga practice
      in addition to standard cancer treatment for people with haematological
      malignancies. SEARCH METHODS: Our search strategy included the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE (1950 to 4th February 2014),
      databases of ongoing trials (controlled-trials.com; clinicaltrials.gov),
      conference proceedings of the American Society of Clinical Oncology, the American
      Society of Hematology, the European Haematology Association, the European
      Congress for Integrative Medicine, and Global Advances in Health and Medicine. We
      handsearched references of these studies from identified trials and relevant
      review articles. Two review authors independently screened the search results.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) of yoga in
      addition to standard care for haematological malignancies compared with standard
      care only. We did not restrict this to any specific style of yoga. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data for
      eligible studies and assessed the risk of bias according to predefined criteria.
      We evaluated distress, fatigue, anxiety, depression and quality of sleep. Further
      outcomes we planned to assess were health-related quality of life (HRQoL),
      overall survival (OS) and adverse events (AE), but data on these were not
      available. MAIN RESULTS: Our search strategies led to 149 potentially relevant
      references, but only a single small study met our inclusion criteria. The
      included study was published as a full text article and investigated the
      feasibility and effect of Tibetan Yoga additional to standard care (N = 20; 1
      person dropped out before attending any classes and no data were collected)
      compared to standard care only (N = 19). The study included people with all
      stages of Hodgkin and non-Hodgkin's lymphoma, with and without current cancer
      treatment. The mean age was 51 years.We judged the overall risk of bias as high
      as we found a high risk for performance, detection and attrition bias.
      Additionally, potential outcome reporting bias could not be completely ruled out.
      Following the recommendations of GRADE, we judged the overall quality of the body
      of evidence for all predefined outcomes as 'very low', due to the methodical
      limitations and the very small sample size.The influence of yoga on HRQoL and OS
      was not reported. There is no evidence that yoga in addition to standard care
      compared with standard care only can improve distress in people with
      haematological malignancies (mean difference (MD) -0.30, 95% confidence interval
      (CI) -5.55 to 4.95; P = 0.91). Similarly, there is no evidence of a difference
      between either group for fatigue (MD 0.00, 95% CI -0.94 to 0.94; P = 1.00),
      anxiety (MD 0.30, 95% CI -5.01 to 5.61; P = 0.91) or depression (MD -0.70, 95% CI
      -3.21 to 1.81; P = 0.58).There is very low quality evidence that yoga improves
      the overall quality of sleep (MD -2.30, 95% CI -3.78 to -0.82; P = 0.002). The
      yoga groups' total score for the Pittsburgh Sleep Quality Index (PSQI) was 5.8
      (+/- 2.3 SD) and better than the total score (8.1 (+/- 2.4 SD)) of the control
      group. A PSQI total score of 0 to 5 indicates good sleep whereas PSQI total score
      6 to 21 points towards significant sleep disturbances. The occurrence of AEs was
      not reported. AUTHORS' CONCLUSIONS: The currently available data provide little
      information about the effectiveness of yoga interventions for people suffering
      from haematological malignancies. The finding that yoga may be beneficial for the
      patients' quality of sleep is based on a very small body of evidence. Therefore,
      the role of yoga as an additional therapy for haematological malignancies remains
      unclear. Further high-quality randomised controlled trials with larger numbers of
      participants are needed to make a definitive statement.

PMID- 24919723
TI  - Oxidized high-density lipoprotein impairs the function of human renal proximal
      tubule epithelial cells through CD36.
AB  - Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects
      in a number of diseases, including chronic kidney disease (CKD); however, the
      mechanisms involved in this process remain unclear. In the present study, we
      investigated the effects of oxidized HDL on renal tubular cells, which play an
      important role in the progression of CKD. Human renal proximal tubule epithelial
      cells (HK-2) were cultured and stimulated with various concentrations of oxidized
      HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized
      HDL enhanced the production of reactive oxygen species (ROS) and upregulated the
      expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent
      manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2
      cells and reduced their migration ability in a dose-dependent manner. Src family
      kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF
      kappaB) were activated following stimulation with oxidized HDL. All these effects
      mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection
      with with CD36 siRNA pior to stimulation with oxidized HDL. These findings
      suggest that oxidized HDL enhances the pro-inflammatory properties and impairs
      the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well
      as through the Src, MAPK and NF-kappaB pathways.

PMID- 24919724
TI  - Expression of testicular androgen receptor in non-obstructive azoospermia and its
      change after hormonal therapy.
AB  - Several trials aimed at improving the sperm retrieval from men with non
      obstructive azoospermia (NOA) by optimizing intratesticular testosterone (ITT)
      have reported partial responses, however, an appropriate level of ITT has not
      been identified. In this study, we examined the expression of the testicular
      androgen receptor (AR) in NOA and investigated its correlation with clinical and
      pathological parameters. Expression of the testicular AR was investigated in 52
      men with NOA and 22 men with obstructive azoospermia (OA). Twenty-two patients
      for whom sperm retrieval failed during microdissection testicular sperm
      extraction (micro-TESE) were enrolled in hormonal therapy using hCG with or
      without recombinant human follicle stimulating hormone (rhFSH) prior to a second
      micro-TESE. Sertoli cells were identified by vimentin immunostaining, and
      positivity in Sertoli cells was used as the AR index. AR immunostaining was
      robust in the nuclei of Sertoli cells [Sertoli cell androgen receptor (SCAR)] in
      both OA and NOA. The mean AR index in NOA was significantly higher than that in
      OA (p < 0.05). In NOA patients, there was no correlation between the AR index and
      the clinical parameters, whereas the AR index of early maturation arrest (MA) was
      significantly lower than that of Sertoli cell only, late MA and
      hypospermatogenesis (p < 0.05). A significant increase in the AR index after
      salvage hormonal therapy was shown, particularly when using rhFSH. The AR index
      in patients from whom spermatozoa could be retrieved at the second micro-TESE
      increased significantly after hormonal therapy. In human testes, the expression
      of AR is dominant in Sertoli cells, and the expression of SCAR is upregulated by
      FSH. Germ cell maturation, especially during spermatogonia to spermatocyte stage,
      has been shown to be SCAR-dependent. Taken together, the results indicate that
      SCAR elevation is closely associated with sperm retrieval after hormonal therapy
      and that FSH-based hormonal therapy is potentially effective in NOA men with MA.

PMID- 24919725
TI  - Courage and character, leaders and legends: an interview with Michael Hess, MD.

PMID- 24919726
TI  - A novel use of intravenous immunoglobulin is not restricted to complement
      hypercatabolism because of factor H deficiency.

PMID- 24919727
TI  - Effect of mannitol on postreperfusion cardiac output and central venous oxygen
      saturation during orthotopic liver transplant: a double-blind randomized clinical
      trial.
AB  - CONTEXT: Attenuating postreperfusion syndrome during orthotopic liver transplant
      is very important for transplant anesthesiologists because of the syndrome's
      complications. Oxygen-derived free radicals play an important role in the genesis
      of postreperfusion syndrome, but the effect of mannitol (a free radical
      scavenger) on attenuating the syndrome is unclear.OBJECTIVES-To investigate the
      effectiveness of infusing mannitol during the anhepatic phase in preventing
      postreperfusion syndrome, as indicated by postreperfusion cardiac output and
      central venous oxygen saturation. DESIGN: In a randomized clinical trial, 53
      patients who had undergone orthotopic liver transplant were allocated to 2
      groups. During the anhepatic phase, patients in the mannitol group received 1g/kg
      mannitol, whereas those in the control group received physiological saline. Mean
      arterial pressure, cardiac output, and central venous oxygen saturation were
      measured before and after the portal vein was declamped. Serum levels of sodium
      and potassium were recorded at baseline and after portal vein declamping.Setting
      Shiraz Organ Transplant Center, Shiraz, Iran. RESULTS: In the mannitol group, no
      significant change was found in mean arterial pressure, cardiac output, and
      central venous oxygen saturation before and after declamping of the portal vein
      (P= .78, P= .59, and P= .83, respectively). However, after declamping in the
      control group, mean arterial pressure, cardiac output, and central venous oxygen
      saturation were significantly lower than before declamping (P=.003, P=.001, and
      P<.001, respectively). No significant change in serum levels of sodium and
      potassium from baseline to after declamping were found in either group.
      CONCLUSION: Infusion of mannitol 1 g/kg during the anhepatic phase was effective
      in attenuating postreperfusion syndrome without stress about hyperkalemia or
      hyponatremia during anesthesia.

PMID- 24919728
TI  - Validation of the Persian version of COOP/WONCA functional health status charts
      in liver transplant candidates.
AB  - CONTEXT: Health-related quality of life is a preferred outcome measure for
      patients with advanced liver disease. The functional health status charts
      developed by the Dartmouth Primary Care Cooperative Information Project
      (COOP)/World Organization of National Colleges, Academies and Academic
      Associations (WONCA) make up a generic instrument for assessing health-related
      quality of life. OBJECTIVE: To translate and validate the Persian version of
      COOP/WONCA in liver transplant candidates and to assess the correlation of Child
      Pugh classification and Model of End Stage Liver Disease (MELD) score with
      quality of life.Setting-The Shiraz liver transplant center, the most active liver
      transplant center in the Middle East. PARTICIPANTS: Consecutive adult outpatients
      waiting for their first liver transplant who attended follow-up visits in the
      pretransplant clinic.Main Outcome Measures-Patients completed COOP/WONCA along
      with the Short Form (SF)-36. Data on the underlying cause of cirrhosis, Child
      Pugh classification, and MELD scores were collected from medical records.
      RESULTS: A Persian version of the COOP/WONCA was accepted by liver transplant
      candidates and showed adequate reliability and validity. Similar domains in
      COOP/WONCA charts and the SF-36 were highly correlated, indicating that construct
      validity of the COOP/WONCA in relation to the SF-36 was good (77% of correlations
      were as expected). Moreover, the exploratory factor analysis could not extract 2
      different quality-of-life factors. These findings provide sufficient evidence to
      conclude that the Persian versions of COOP/WONCA charts and the SF-36 measure the
      same constructs of health-related quality of life and can be used
      interchangeably. Four of the 6 COOP/WONCA charts did not allow discrimination
      between groups of patients according to Child Pugh classification, indicating
      poor known group validity.

PMID- 24919729
TI  - Lung transplant or bust: patients' recommendations for ideal lung transplant
      education.
AB  - CONTEXT: Effective lung transplant education helps ensure informed decision
      making by patients and better transplant outcomes. OBJECTIVE: To understand the
      educational needs and experiences of lung transplant patients. DESIGN: Mixed
      method study employing focus groups and patient surveys. SETTING: Barnes-Jewish
      Hospital in St Louis, Missouri. PATIENTS: 50 adult lung transplant patients: 23
      pretransplant and 27 posttransplant. MAIN OUTCOME MEASURES: Patients' interest in
      receiving specific transplant information, the stage in the transplant process
      during which they wanted to receive the education, and the preferred format for
      presenting the information. RESULTS: Patients most wanted information about how
      to sustain their transplant (72%), when to contact their coordinator immediately
      (56%), transplant benefits (56%), immunosuppressants (54%), and possible out-of
      pocket expenses (52%). Patients also wanted comprehensive information early in
      the transplant process and a review of a subset of topics immediately before
      transplant (time between getting the call that a potential donor has been found
      and getting the transplant). Patients reported that they would use Internet
      resources (74%) and converse with transplant professionals (68%) and recipients
      (62%) most often. DISCUSSION: Lung transplant patients are focused on learning
      how to get a transplant and ensuring its success afterwards. A comprehensive
      overview of the evaluation, surgery, and recovery process at evaluation onset
      with a review of content about medications, pain management, and transplant
      recovery repeated immediately before surgery is ideal.

PMID- 24919730
TI  - Laparoscopic microwave thermal ablation for late recurrence of local
      hepatocellular carcinoma after liver transplant: case report.
AB  - Liver transplant is the preferred treatment for hepatocellular carcinoma in
      patients with cirrhosis, as both neoplastic and cirrhotic liver tissue can be
      removed. Treatment of recurring neoplasms is a difficult issue, especially in
      long-term survivors of liver transplant. No consensus has been reached on the
      treatment of recurrent hepatocellular carcinoma. Although patients with
      extrahepatic metastases are generally not candidates for local therapy,
      successful multimodal salvage therapy including resection or ablation can be
      achieved in liver transplant recipients with local recurrence of hepatocellular
      carcinoma. Microwave ablation is safe and effective for treating unresectable
      hepatocellular carcinoma, achieving excellent results in local disease down
      staging or as a "bridge" to liver transplant, with no significant differences in
      local recurrence and complications compared with the more commonly used
      radiofrequency ablation. A patient with local recurrence of hepatocellular
      carcinoma 36 months after liver transplant for multifocal hepatocellular
      carcinoma and cirrhosis due to hepatitis C was successfully treated with
      laparoscopic microwave ablation without any postoperative complications. The
      patient is disease free 24 months after microwave ablation. 

PMID- 24919731
TI  - Relationship between fragmented QRS complex and left ventricular systolic and
      diastolic function in kidney transplant patients.
AB  - BACKGROUND: Kidney transplant is a most important replacement therapy. It reduces
      cardiovascular mortality and morbidity but does not fully correct impairments in
      cardiac function. Fragmented QRS (fQRS) complex includes various RSR' patterns
      with different QRS complex morphologies on electrocardiograms. OBJECTIVE: To
      analyze fQRS frequency and the relationship between fQRS and left ventricular
      function in kidney transplant patients. METHOD: -After demographic data on 39
      kidney transplant patients were recorded and biochemical parameters were
      investigated, electrocardiograms were evaluated for the presence of fQRS. Left
      ventricular ejection fraction, mitral annular plane systolic excursion, peak
      early diastolic mitral annular velocities, late diastolic mitral annular
      velocities, and systolic mitral annular velocity were analyzed. RESULTS:
      Fragmented QRS was detected in 16 patients. A history of hypertension was
      associated with the presence of fQRS. Patients with fQRS had significantly lower
      systolic and peak early diastolic mitral annular velocities, mitral annular plane
      systolic excursion, and left ventricular ejection fraction than did patients
      without fQRS (P= .03, .01, <.001, and .03, respectively). CONCLUSION: Detection
      of fQRS on electrocardiograms may be useful in predicting systolic and diastolic
      dysfunction of the left ventricle in kidney transplant patients.

PMID- 24919732
TI  - Hispanic/Latino concerns about living kidney donation: a focus group study.
AB  - CONTEXT: Given the shortage of kidneys for transplant, living kidney donation
      (LKD) is increasingly used to expand the organ donor pool. Although
      Hispanics/Latinos need disproportionately more kidney transplants, they receive a
      smaller proportion of living donor kidney transplants than other ethnic/racial
      groups. OBJECTIVE: To assess Hispanics' awareness, perceptions, misconceptions,
      cultural beliefs, and values about and barriers to LKD. DESIGN: Nine focus groups
      were conducted with 76 adult Hispanics in Chicago, Illinois, between January and
      March 2012. PARTICIPANTS: Focus groups included kidney transplant recipients,
      living kidney donors, dialysis patients, and the general Hispanic public.
      RESULTS: Several themes emerged as perceived barriers to LKD. Many participants
      identified knowledge deficits about LKD, expressing uncertainty about the
      differences between LKD and deceased donation, and whether kidney disease
      simultaneously afflicts both kidneys. Many believed that donors experience
      dramatically shorter life expectancies, are unable to have children, and are more
      susceptible to kidney disease after donating. Recipients and donors reported that
      family members were involved in discussions about the donor's decision to donate,
      with some family members discouraging donation. Financial barriers cited included
      fear of becoming unable to work, losing one's job, or being unable to pay
      household bills while recovering. Participants also identified logistic barriers
      for undocumented immigrants (eg, the inability to obtain government insurance for
      transplant candidates and uncertainty about their eligibility to donate). Donors
      desired information about optimizing self-care to promote their remaining
      kidney's health. Culturally competent interventions are needed to redress
      Hispanics' knowledge deficits and misconceptions and reduce LKD disparities among
      Hispanics.

PMID- 24919733
TI  - Independent donor ethical assessment: aiming to standardize donor advocacy.
AB  - Living organ donation has become more common across the world. To ensure an
      informed consent process, given the complex issues involved with organ donation,
      independent donor advocacy is required. The choice of how donor advocacy is
      administered is left up to each transplant center. This article presents the
      experience and process of donor advocacy at University of Texas Southwestern
      Medical Center administered by a multidisciplinary team consisting of physicians,
      surgeons, psychologists, medical ethicists and anthropologists, lawyers, a
      chaplain, a living kidney donor, and a kidney transplant recipient. To ensure
      that advocacy remains fair and consistent for all donors being considered, the
      donor advocacy team at University of Texas Southwestern Medical Center developed
      the Independent Donor Ethical Assessment, a tool that may be useful to others in
      rendering donor advocacy. In addition, the tool may be modified as circumstances
      arise to improve donor advocacy and maintain uniformity in decision making. 

PMID- 24919734
TI  - Information sources, donation knowledge, and attitudes toward transplant
      recipients in Australia.
AB  - CONTEXT: Knowledge is linked consistently with organ donation attitudes,
      willingness, and consent. Negative information about donation and the recipients
      of donation can affect public opinion and donation willingness. However, it is
      unclear which information sources are most important in forming knowledge,
      particularly in Australia where little prior research exists. OBJECTIVES: To
      identify information sources that may inform Australians' organ donation
      knowledge and attitudes toward transplant recipients. PARTICIPANTS: 1487
      Australian residents aged 18 years or older who completed an online survey. MAIN
      OUTCOME MEASURES: Self-reported knowledge, information sources, and attitudes
      toward transplant recipients. RESULTS: Participants felt fairly well informed
      about organ donation, particularly if they registered donation wishes, were
      female, and were older. More than half reported their driver's license,
      television news, and discussion with family/friends as donation information
      sources. However, information sources contributing to knowledge were personal
      experience, online, hospital, government campaign, discussion with
      family/friends, Medicare, doctor's surgery, and the newspaper. Differences based
      on registration status, sex, and age, were found. Discussion with family/friends
      and movies or television shows, as well as not having seen information in a
      newspaper or doctor's surgery, contributed to positive attitudes toward
      recipients, although the variance explained was small. CONCLUSIONS: People felt
      more informed by personal, medical, and government information sources than by
      mass media. Family discussion was not only a common information source but also
      contributed significantly and positively to both donation knowledge and attitudes
      toward recipients. Further exploration of information sources contributing to
      donation knowledge and community attitudes toward transplant recipients among
      young men is needed.

PMID- 24919735
TI  - Influence of scientific worldviews on attitudes toward organ transplants:
      national survey data from the United States.
AB  - CONTEXT: Public acceptance of routine medical procedures is nearly universal, but
      controversy over dramatic or invasive procedures like transplants is common.
      OBJECTIVES: To assess the distributions and organization of public opinion on
      organ transplant and to discover the magnitude of the direct and indirect impacts
      of religion, scientific knowledge, and acceptance of evolution on individuals'
      support for organ transplant. PARTICIPANTS: A representative sample (N=2069) of
      the US adult, English-speaking population in 2009. INTERVENTION: Participants
      were administered the International Social Science Survey/USA 2009. RESULTS:
      Organ transplants were warmly endorsed by most Americans in 2009, as earlier, but
      support is not universal. Confirmatory factor analysis shows that Americans'
      opinions on heart, kidney, and pancreas transplants all reflect the same
      underlying attitude toward major organ transplants. Structural equation modeling
      shows that scientific knowledge is the most important influence on these
      attitudes, with more knowledgeable persons being more supportive. Acceptance of
      the theory of evolution is the second most important factor, also associated with
      greater support for transplant. Growing up in a church-going family encourages
      people to support organ transplant, even after adjusting for other influences.
      Otherwise denomination and religious belief have only small indirect influences.
      Demographic differences are small. CONCLUSIONS: These results provide clues about
      future trends. A religious revival, were it to occur, would not be likely to
      alter support for transplants. If public knowledge of science continues to
      increase, or acceptance of the theory of evolution grows, support for transplant
      will most likely increase.

PMID- 24919736
TI  - Expanding the role of pharmacists and pharmacy students in the promotion of organ
      donation awareness.
AB  - The gap between supply and demand for available organs has resulted in numerous
      deaths of patients on the transplant waiting list each year. Given the
      substantial public health impact of the organ shortage crisis, efforts have been
      focused on the use of educational interventions aimed both at the public and
      health care professionals to spread awareness of the disparity in organ supply
      and demand and ultimately improve organ donation rates. Transplant pharmacists
      are fundamental members of transplant multidisciplinary teams and are expected to
      promote organ and tissue awareness in an effort to decrease the morbidity and
      mortality of patients on the transplant waiting list. The role of pharmacists and
      pharmacy students in the promotion of organ donation awareness is expanding. 

PMID- 24919737
TI  - Risk factors for perioperative complications in hand-assisted laparoscopic donor
      nephrectomy.
AB  - Living donor kidney transplant is the preferred treatment for end-stage renal
      disease; however, the shortage of kidney donors remains a big problem. One of the
      major reasons for the shortage of living donors is the risk of potentially
      serious surgical complications of a procedure in which the donor has no personal
      medical benefit. Therefore it is important to understand the risk factors for
      perioperative complications associated with donor nephrectomy. Hand-assisted
      laparoscopic donor nephrectomy is the preferred approach for kidney procurement
      in many medical centers. This review gives an overview of the risk factors in
      donor nephrectomy and more specifically in hand-assisted laparoscopic donor
      nephrectomy. 

PMID- 24919738
TI  - Successful kidney transplant from methanol-intoxicated donors.
AB  - The well-described disparity between the need for and the supply of organs
      suitable for transplant is growing. Because of this disparity, mortality of
      patients listed for transplant is increasing. Donors who die of intoxication
      (including victims of methanol poisoning) represent less than 1% of suitable
      donors and might be used to increase the supply of organs. They are often not
      accepted as donors by transplant specialists, because of concerns about patients'
      outcomes with these grafts. Three cases of fatal methanol intoxication that
      resulted in transplants of 6 kidneys are evaluated. 

PMID- 24919739
TI  - Pursuing expanded criteria donors as candidates for kidney donation after
      circulatory death.
AB  - Of the 119 310 people on the national transplant waiting list, 97 280 people are
      waiting for kidneys. There simply are not enough organs to meet the demand.
      Recognizing that 64% of the people waiting for kidney transplants are at least 50
      years old, this organ procurement organization embarked on a study to evaluate
      the potential of increasing the number of viable kidneys available for transplant
      by pursuing expanded criteria donors as donation after circulatory death
      (ECD/DCD) candidates. Pursuing ECD/DCD donors resulted in 24 additional donors
      (50-67 years old), 48 kidneys recovered, 30 kidneys transplanted into 26
      recipients (44-74 years old), 7 kidneys placed for research, and 11 kidneys
      discarded, yielding an overall 62% transplant rate, 15% research rate, and 23%
      discard rate. The overall discard rate including all donors in all
      classifications during the study period was 13.1% (122 discards from 928 kidneys)
      compared with 12.6% (111 discards from 880 kidneys) when the study set was
      excluded. Although ECD/DCD donors still had the highest discard rates of all the
      groups, the 0.5% increase in the overall discard rate due to pursuing ECD/DCD
      kidneys was considered insignificant when compared with the benefit of the 30
      additional kidneys transplanted. Including potential ECD/DCD patients in the
      donor pool increases the number of viable kidneys available for transplant
      without significantly increasing the overall kidney discard rates. 

PMID- 24919740
TI  - Impact of organ donation education on US undergraduate nursing students.
AB  - Experts advocate educational programs addressing misinformation regarding
      donation decisions to increase the potential donor pool. However, few researchers
      have measured outcomes with nursing students. The purpose of this study was to
      evaluate the impact of an educational intervention on nursing students'
      knowledge, attitudes, registering as an organ donor, and family discussions. This
      quasi-experimental study used a pretest-posttest design with a control group. The
      research group consisted of 42 volunteers and the control group consisted of 73
      volunteers. The written survey included 15 true-false knowledge items and 8
      Likert items asking about attitude toward donation, registering as an organ
      donor, and family discussion. Normally distributed data showed no significant
      differences between groups on the pretest. The research group had no change in
      knowledge level 3 months later, but the control group had a significantly
      decreased knowledge level at that point. More members of the research group than
      the control group registered as organ donors after the intervention (chi2 = 4.5,
      P= .03). The control group had no change in registering as an organ donor between
      the pretest and posttest. Family discussions did not differ significantly from
      pretest to posttest in either group. One lecture/laboratory experience did make a
      difference in registering as an organ donor but not in discussing the decision
      with family members. Students can learn about organ donation from more than one
      specific class. Recommendations for educators and future research are provided. 

PMID- 24919741
TI  - Online education for transplant professionals.

PMID- 24919742
TI  - Posterior reversible encephalopathy syndrome in leukemic children: a sensitive
      issue.
AB  - Posterior reversible encephalopathy syndrome (PRES) is an acute central nervous
      system disorder characterized by reversible brain vasogenic edema. We report here
      a new case of a nine-year-old boy with B-cell acute lymphoblastic leukemia (B
      ALL) who developed PRES secondary to induction chemotherapy including
      dexamethasone (dexamethasone(r)), vincristine (oncovin((r))), daunorubicin
      (adriblastine((r))) and intrathecal injection. Cerebral magnetic resonance
      imaging (MRI) showed high signal intensity on T2 at cortical and sub cortical
      region of parieto-frontal and parieto-occipital lobes. The patient was put under
      sodium valproate (depakine((r))) and we decided to continue dexamethasone
      (dexamethasone((r))) and daunorubicin (adriblastine((r))) injection. The MRI,
      after four weeks, was normal. So, we resumed vincristine (oncovin((r))) and we
      started L-asparaginase injections. Then, the outcome was favorable. The treatment
      of PRES is based on the withdrawal of the triggering factor to avoid the risk of
      irreversible lesions. But, due to the severity of leukemia the discontinuation of
      chemotherapy is difficult because of the risk of disease progression.

PMID- 24919743
TI  - Dispersion of T1 and T2 nuclear magnetic resonance relaxation in crude oils.
AB  - Crude oils, which are complex mixtures of hydrocarbons, can be characterized by
      nuclear magnetic resonance diffusion and relaxation methods to yield physical
      properties and chemical compositions. In particular, the field dependence, or
      dispersion, of T1 relaxation can be used to investigate the presence and dynamics
      of asphaltenes, the large molecules primarily responsible for the high viscosity
      in heavy crudes. However, the T2 relaxation dispersion of crude oils, which
      provides additional insight when measured alongside T1, has yet to be
      investigated systematically. Here we present the field dependence of T1-T2
      correlations of several crude oils with disparate densities. While asphaltene and
      resin-containing crude oils exhibit significant T1 dispersion, minimal T2
      dispersion is seen in all oils. This contrasting behavior between T1 and T2
      cannot result from random molecular motions, and thus, we attribute our
      dispersion results to highly correlated molecular dynamics in asphaltene
      containing crude oils.

PMID- 24919744
TI  - Correlation between erection hardness score and nocturnal penile tumescence
      measurement.
AB  - INTRODUCTION: The Erection Hardness Score (EHS) and the Sexual Health Inventory
      for men (SHIM) are patient-reported outcome scoring systems for erectile
      function. It is unclear which is more reliable for predicting the objective
      erectile function. AIM: The aim of this study was to evaluate whether the EHS
      could predict objective erectile function by measuring the maximal penile
      circumferential change (MPCC) with an erectometer. METHODS: The study included 98
      patients who visited our clinic from 2005 to 2010. The erectile function was
      evaluated using the SHIM, EHS, and MPCC. The MPCC was measured with the largest
      circumferential change of three consecutive occurrences of nocturnal penile
      tumescence (NPT) determined using the erectometer. MAIN OUTCOME MEASURES: We
      defined erectile dysfunction (ED) as MPCC < 20 mm and carried out multivariate
      analysis using logistic regression analysis to clarify the predictors for ED,
      with the variables including age, the SHIM score, and the EHS. We compared the
      tendency for MPCC >= 20 mm when EHS was 3 or more with that when EHS was 2 or
      less. RESULTS: The median age of the patients was 59.5 years (range 18-83). In
      logistic regression analysis, the EHS was the only predictor for ED with MPCC <
      20 mm. The mean EHS in the MPCC < 20 mm group was 1.64 +/- 0.20 (mean +/- SEM)
      and that in the MPCC >= 20 mm group was 2.46 +/- 0.13 (P = 0.0018). There was a
      correlation between the EHS and the MPCC (correlation coefficient = 0.33). In
      comparison with the group having an EHS of 2 or less, that with an EHS of 3 or
      more tended to have MPCC >= 20 mm (P = 0.013). CONCLUSIONS: The EHS was
      correlated with the MPCC. The EHS represents the objective erectile function
      shown by the measurement of NPT.

PMID- 24919746
TI  - The other side of childhood disability. Foreword.

PMID- 24919745
TI  - More severe upper gastrointestinal symptoms associated with non-erosive reflux
      disease than with erosive gastroesophageal reflux disease during maintenance
      proton pump inhibitor therapy.
AB  - BACKGROUND: During maintenance proton pump inhibitor (PPI) therapy, patients with
      gastroesophageal reflux disease (GERD) sometimes complain of upper
      gastrointestinal symptoms. AIM: To evaluate upper gastrointestinal symptoms in
      patients on maintenance PPI therapy for erosive GERD or non-erosive reflux
      disease (NERD) without endoscopic mucosal breaks by using a new questionnaire.
      METHODS: At Gunma University Hospital over a 12-month period during 2011-2012, we
      enrolled 30 consecutive patients with erosive GERD and 46 patients with NERD. All
      patients had been on maintenance PPI therapy for more than 1 year. We used the
      modified frequency scale for the symptoms of GERD (mFSSG) questionnaire to assess
      upper gastrointestinal symptoms. We also asked patients about their satisfaction
      with maintenance therapy and whether they wished to change their current PPI.
      RESULTS: The NERD patients had significantly higher symptom scores than the
      erosive GERD patients. There was no difference in the treatment satisfaction rate
      between patients with erosive GERD and NERD, but more patients with NERD wanted
      to change their PPI therapy. There was no difference in the mFSSG score between
      NERD patients who wished to change their current PPI therapy and those who were
      satisfied with it. CONCLUSIONS: During maintenance PPI therapy, upper
      gastrointestinal symptoms were more severe in NERD patients than in patients with
      erosive GERD. NERD patients often wished to change their PPI therapy, but this
      was not dependent on the severity of their upper GI symptoms.

PMID- 24919749
TI  - Obesity and type 2 diabetes in children: epidemiology and treatment.
AB  - The incidence of overweight and obesity among children has increased dramatically
      in recent decades, with about one-third of children in the U.S. currently being
      either overweight or obese. Being overweight in early childhood increases risk
      for later obesity. There is evidence for the efficacy of family-based behavioral
      treatment to control weight and improve health outcomes. Obesity-related health
      risks have been documented, including metabolic syndrome. There is also
      increasing incidence of type 2 diabetes (T2D) among youth in recent years, with
      obesity and family history of T2D generally present. Lower income and ethnic
      minority status are associated with both obesity and T2D in youth. Most youth
      with T2D do not achieve optimal glycemic control, and are at high risk for later
      health complications. Obesity and T2D represent significant public health issues
      with potentially great personal and societal cost. Research addressing the
      prevention of obesity and T2D among youth is urgently needed.

PMID- 24919750
TI  - Anti-VEGF therapy for diabetic macular edema.
AB  - Vascular endothelial growth factor (VEGF) plays a pivotal role in the development
      of diabetic macular edema (DME), the leading cause of vision loss among working
      aged individuals. A decade of clinical trials demonstrated that drugs that bind
      soluble VEGF restore the integrity of the blood-retinal barrier, resolve macular
      edema, and improve vision in most patients with DME. Four drugs (pegaptanib,
      ranibizumab, bevacizumab, and aflibercept) effectively treat DME when
      administered by intravitreal injections. Only ranibizumab has received U.S. Food
      and Drug Administration (FDA) approval for DME, but bevacizumab is commonly used
      off-label, and an FDA application for aflibercept is pending. Effective treatment
      requires repeated injections, although recent data suggest that the treatment
      burden diminishes after 1 year. Intravitreal therapy is generally safe, although
      the incidence of systemic thromboembolic events varies among trials.

PMID- 24919751
TI  - Novel urinary biomarkers in early diabetic kidney disease.
AB  - In diabetic kidney disease, detection of urinary albumin is recommended to aid in
      diagnosis, evaluate disease severity, and determine effects of therapy. However,
      because typical histopathologic changes in diabetic kidney disease or early
      progressive renal decline may occur in patients with normoalbuminuria, urinary
      albumin may not be sufficient to identify patients with early-stage diabetic
      kidney disease or to predict its progression. Therefore, intensive efforts have
      been made to identify novel noninvasive urinary biomarkers to discriminate
      patients with a higher risk of end-stage renal failure. Because diabetic kidney
      disease progression is associated with the extent of histologic changes in the
      glomeruli and the degree of tubulointerstitial changes, urinary biomarkers that
      accurately reflect the degree of histopathologic damage may be excellent
      biomarkers. This review article summarizes the clinical significance of new
      urinary biomarkers in the early detection of diabetic kidney disease. 

PMID- 24919752
TI  - The associations of adipokines with selected markers of the renin-angiotensinogen
      aldosterone system: the multi-ethnic study of atherosclerosis.
AB  - Among obese individuals, increased sympathetic nervous system (SNS) activity
      results in increased renin and aldosterone production, as well as renal tubular
      sodium reabsorption. This study determined the associations between adipokines
      and selected measures of the renin-angiotensinogen-aldosterone system (RAAS). The
      sample consisted of 1970 men and women from the Multi-Ethnic Study of
      Atherosclerosis who were free of clinical cardiovascular disease at baseline and
      had blood assayed for adiponectin, leptin, plasma renin activity (PRA) and
      aldosterone. The mean age was 64.7 years and 50% were female. The mean (s.d.) PRA
      and aldosterone were 1.45 (0.56) ng ml(-1) and 150.1 (130.5) pg ml(-1),
      respectively. After multivariable adjustment, a 1-s.d. increment of leptin was
      associated with a 0.55 ng ml(-1) higher PRA and 8.4 pg ml(-1) higher aldosterone
      (P<0.01 for both). Although adiponectin was not significantly associated with PRA
      levels, the same increment in this adipokine was associated with lower
      aldosterone levels (-5.5 pg ml(-1), P=0.01). Notably, the associations between
      aldosterone and both leptin and adiponectin were not materially changed with
      additional adjustment for PRA. Exclusion of those taking antihypertensive
      medications modestly attenuated the associations. The associations between leptin
      and both PRA and aldosterone were not different by gender but were significantly
      stronger among non-Hispanic Whites and Chinese Americans than African and
      Hispanic Americans (P<0.01). The findings suggest that both adiponectin and
      leptin may be relevant to blood pressure regulation via the RAAS, in that the
      associations appear to be robust to antihypertension medication use and that the
      associations are likely different by ethnicity. 

PMID- 24919753
TI  - Profile of interdialytic ambulatory blood pressure in a cohort of Chinese
      patients.
AB  - Management of hypertension is one of the fundamental interventions in dialysis
      patients. However, the profile of interdialytic blood pressure (BP) in Chinese
      dialysis patients remains elusive. We aim to investigate this issue as well as
      the effect of antihypertensive medication in this population. We performed 44-h
      ambulatory BP in 90 patients on maintenance hemodialysis. Patients were
      classified as 'dipping', 'non-dipping' or 'reverse-dipping' based on night/day
      ratio (N/D) of systolic BP on nondialysis day. The prevalence of blunted
      circadian BP pattern was strikingly high (92.2%), with more than half of the
      patients (55.6%) classified as reverse-dipping. There was a close association
      between high erythropoietin (EPO) dose used and deteriorated circadian rhythm.
      Patients in the dipping group also displayed a dipping state for heart rate (HR)
      compared with the other two groups (N/D of HR: 81.5 +/- 6.6 vs 92.1 +/- 6.0 and
      91.3 +/- 10.7, P=0.02). Only 26.7% patients had a controlled nocturnal BP.
      Patients with bedtime dosing had lower N/D of systolic BP compared with patients
      without (100.1 +/- 7.0 vs 105.2 +/- 7.1, P=0.01). Non-dipping and reverse-dipping
      are highly prevalent in Chinese patients. EPO use and autonomic dysfunction may
      contribute to the blunted circadian rhythm. More tightly control of nighttime BP
      is an urgent need and bedtime dosing may be beneficial.

PMID- 24919754
TI  - Transfer of peanut IgE sensitisation after combined pancreas-kidney transplant.
AB  - BACKGROUND: The transfer of peanut allergy has been reported following solid
      organ transplantation. OBJECTIVE: Present a case of peanut sensitization
      following combined pancreas-and-kidney transplantation. METHODS: Circulating
      specific IgE against peanut were measured in serum samples collected from the
      transplant recipient 1 month before transplantation, and 1, 3 and 6 months after
      transplantation. Skin tests were performed 1, 3 and 6 months following
      transplant. RESULTS: The organ recipient's pre-transplant peanut IgE levels were
      negative. At 1 month post-transplant, the patient had a 6 mm skin test to peanut
      and had serum IgE to peanut Arah1 of 0.79 kU/L. At 3 months, skin test size and
      IgE to peanut Arah1 decreased to 4 mm, and 0.69 kU/L respectively. At 6 months,
      the patient's skin test and IgE to peanuts were negative. At that time, the
      patient underwent a peanut food challenge without a clinical reaction to suggest
      allergy. CONCLUSION AND CLINICAL RELEVANCE: We report the development of IgE
      peanut sensitization in a recipient of a combined pancreas and kidney
      transplantation. Increasing awareness of this allergen sensitization following
      transplantation may help prevent serious allergic reactions in transplant
      recipients.

PMID- 24919756
TI  - Cloning and characterization of SnRK2 subfamily II genes from Nicotiana tabacum.
AB  - SnRK2 is a plant-specific protein kinase family involved in abiotic stress
      signalling. In this study, NtSnRK2.1, NtSnRK2.2, and NtSnRK2.3, were cloned from
      tobacco by in silico cloning and reverse transcription PCR. The three protein
      kinases were classed into subfamily II of the SnRK2 family using a phylogenetic
      tree and C-terminus analysis. Subcellular localization revealed NtSnRK2s in the
      nuclear and cytoplasmic compartments. Dynamic expression of NtSnRK2s in tobacco
      plants that were exposed to drought, salt, or cold stressors were characterised
      using quantitative real-time PCR. It was revealed that the three genes showed
      similar patterns of transcription under abiotic stress responses; there was
      evidence NtSnRK2s participated in abscisic acid-dependent signalling pathways.
      NtSnRK2.1-3 responded much faster to drought and salt than to cold stress. To
      investigate the role of NtSnRK2s under abiotic stresses, NtSnRK2.1 gene was over
      expressed in tobacco. A stress tolerance assay showed that tobacco plants that
      over-expressed NtSnRK2.1 plants had greater salt tolerance. The results indicate
      that NtSnRK2s are involved in abiotic stress response pathways. 

PMID- 24919757
TI  - Single nucleotide polymorphisms in genes encoding toll-like receptors 7, 8 and 9
      in Danish patients with systemic lupus erythematosus.
AB  - Several studies indicate a role for toll-like receptors (TLRs) in the
      pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate the
      risk of SLE and typical clinical and serological manifestations of SLE
      potentially conferred by selected single nucleotide polymorphisms (SNPs) of genes
      encoding TLR7, TLR8, and TLR9. Using a multiplexed bead-based assay, we analyzed
      eight SNPs in a cohort of 142 Danish SLE patients and a gender-matched control
      cohort comprising 443 individuals. Our results showed an association between the
      rs3853839 polymorphism of TLR7 and SLE (G vs. C, P = 0.008, OR 1.60, 95 % CI 1.12
      2.27 in females; P = 0.02, OR 4.50, 95 % CI 1.18-16.7 in males) confirming recent
      findings in other populations. Additionally, an association between the rs3764879
      polymorphism of TLR8 and SLE (G vs. C, P < 0.05, OR 1.36, 95 % CI 0.99-1.86 in
      females; P = 0.06, OR 4.00, 95 % CI 0.90-17.3 in males) was found. None of the
      other investigated SNPs were associated with SLE but several SNPs were associated
      with clinical and serological manifestations. In summary, a previously shown
      association between the rs3853839 SNP of TLR7 and SLE in Asian patients was also
      found in Danish patients. Together with the association of several other SNPs of
      TLR8 and TLR9 with various clinical and serological manifestations of SLE these
      findings corroborate the pathogenic significance of TLRs in SLE.

PMID- 24919758
TI  - Validation of pharyngeal findings on sleep nasopharyngoscopy in children with
      snoring/sleep disordered breathing.
AB  - OBJECTIVE: To validate the pharyngeal findings in sleep nasopharyngoscopy (SNP)
      of children with snoring - sleep disordered breathing (S-SDB). DESIGN:
      Prospective agreement diagnostic study on retrospective data. METHODS: We
      conducted an inter-and intra-rater agreement study on video documentations of SNP
      performed on children (non-syndromic, complex, or operated upon) who presented
      with S-SDB. The videos featured various pharyngeal findings (normal, collapse,
      mixed or obstruction). Three 'non-expert' raters at various stages in their
      otolaryngological careers rated the videos independently, and on two separate
      occasions following an instructional session. We calculated both weighted and non
      weighted linear kappa. RESULTS: Each independent observer rated sixty-one videos
      (2 weeks apart). Intra-observer agreement was 0.64 +/- 0.08 (95% CI 0.48-0.81),
      0.74 +/- 0.07 (95% CI 0.60-0.88), 0.59 +/- 0.08 (95% CI 0.43-0.74), for raters 1,
      two and three. Weighted kappa was 0.6 +/- 0.1 (95% CI 0.41-0.79), 0.8 +/- 0.06
      (95% CI 0.7-0.92), 0.7 +/- 0.07 (95% CI 0.57-0.83), respectively. Inter-rater
      agreements between raters one and two, two and three, three and four were 0.83 +/
      0.06 (95% CI 0.71-0.95), 0.52 +/- 0.08 (95% CI 0.36-0.70), and 0.53 +/- 0.08
      (95% CI 0.37-0.69), respectively. Weighted kappa was 0.83 +/- 0.073 (95% CI 0.69
      0.98), 0.68 +/- 0.06 (95% CI 0.56-0.79), and 0.64 +/- 0.07 (95% CI 0.49-0.78),
      respectively. CONCLUSIONS: This is the first validation of pharyngeal findings on
      SNP in children. It is based on a four types' classification. Overall
      reproducibility amongst the three raters and their agreement was moderate to
      good. Further work should be phase four trials investigating the impact on
      outcome.

PMID- 24919759
TI  - Japanese cedar pollinosis: discovery, nomenclature, and epidemiological trends.
AB  - The history of pollinosis in Japan before the discovery of Japanese cedar
      pollinosis was presented in part I in this paper. Until early 1960s, it was
      believed that there was no pollinosis in Japan except one case of ragweed
      pollinosis. The summary of how the Japanese cedar pollinosis was discovered and
      named was presented in part II, by referring to the paper in which we reported
      the presence of Japanese cedar pollinosis for the first time. The epidemiology
      after the discovery of Japanese cedar pollinosis was presented in part III. The
      number of the patients suffering from Japanese cedar pollinosis gradually
      increased since the 1970s. The annual incidence rate of the pollinosis had
      correlations with the dispersed pollen count per year. The prevalence rate of the
      patients with Japanese cedar pollinosis increased from 16.2% in 1998 to 26.5% in
      2008 by the nationwide survey. The prevalence rate of the patients with Japanese
      cedar pollinosis in Tokyo metropolitan area was 10% from 1983 to 1987, 19.4% in
      1996, and 28.2% in 2006. The prospects of current research and future studies
      were discussed in parts IV and V.

PMID- 24919760
TI  - Comprehensive whole-body counter surveys of Miharu-town school children for three
      consecutive years after the Fukushima NPP accident.
AB  - Comprehensive whole-body counter surveys covering over 93% of the school children
      between the ages of 6 and 15 in Miharu town, Fukushima Prefecture, have been
      conducted for three consecutive years, in 2011, 2012 and 2013. Although the
      results of a questionnaire indicate that approximately 60% of the children have
      been regularly eating local or home-grown rice, in 2012 and 2013 no child was
      found to exceed the (137)Cs detection limit of 300 Bq/body. 

PMID- 24919761
TI  - Distributions and biomass of benthic ciliates, foraminifera and amoeboid protists
      in marine, brackish, and freshwater sediments.
AB  - The quantitative importance of ciliates, foraminifers, and amoebae was
      investigated in marine, brackish, and freshwater sediments from 15 littoral
      stations. Total protozoan communities were usually dominated by ciliates in term
      of abundance, while amoebae often dominated in terms of biomass. Applying the
      biomass-metabolic rate equation, ciliates, amoebae, and foraminifera were
      estimated to contribute 66% of the total abundance and 33% of the biomass, but up
      to 55% of the combined metabolic rate to the micro- and meiobenthos in the 15
      sediments. Statistical analyses using ciliate data demonstrated: (1) species
      composition and community structures represented significant differences between
      freshwater and marine/brackish sediments, and subsequently between temperate and
      arctic sampling sites; (2) the occurrence of dominant ciliates and their
      allocation to feeding types indicated that herbivory was the most common feeding
      strategy in these sediments; (3) multivariate analyses showed all of the tested
      environmental factors (temperature, salinity, silt/clay, carbon, nitrogen, and
      chlorophyll a) to be important to varying degrees, but especially the combination
      of salinity, temperature, and silt/clay. Multiple factor effects or comprehensive
      influences might be important in regulating the distribution of protozoa in
      sediments. The importance of protozoa in sediment systems and the potential
      ecological significance of cysts are discussed. 

PMID- 24919762
TI  - Explaining end-users' intentions to use innovative medical and food biotechnology
      products.
AB  - Low public acceptance hinders the successful introduction of biotechnological
      innovations, such as genetically modified foods or vaccinations against
      infectious diseases. Earlier studies indicated that a lack of knowledge is not a
      key barrier to acceptance. This was confirmed in the current study, which
      examined an integrated theoretical model tested among 579 participants from the
      Dutch public. The results suggest that communication strategies should instead
      target attitudes, social norms, and risk perceptions, and appeal to people's
      tendency (or lack thereof) to be innovative. 

PMID- 24919763
TI  - Rapid skeletal turnover in a radiographic mimic of osteopetrosis.
AB  - Among the high bone mass disorders, the osteopetroses reflect osteoclast failure
      that prevents skeletal resorption and turnover, leading to reduced bone growth
      and modeling and characteristic histopathological and radiographic findings. We
      report an 11-year-old boy with a new syndrome that radiographically mimics
      osteopetrosis (OPT), but features rapid skeletal turnover. He presented at age 21
      months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs
      showed a dense skull, generalized osteosclerosis and cortical thickening,
      medullary cavity narrowing, and diminished modeling of tubular bones. His serum
      alkaline phosphatase was >5000 IU/L (normal <850 IU/L). After partial resection,
      the granuloma re-grew but then regressed and stabilized during 3 years of
      uncomplicated pamidronate treatment. His hyperphosphatasemia transiently
      diminished, but all bone turnover markers, especially those of apposition,
      remained elevated. Two years after pamidronate therapy stopped, bone mineral
      density (BMD) Z-scores reached +9.1 and +5.8 in the lumbar spine and hip,
      respectively, and iliac crest histopathology confirmed rapid bone remodeling.
      Serum multiplex biomarker profiling was striking for low sclerostin. Mutation
      analysis was negative for activation of lipoprotein receptor-related protein 4
      (LRP4), LRP5, or TGFbeta1, and for defective sclerostin (SOST), osteoprotegerin
      (OPG), RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number
      variation. Studies of his nonconsanguineous parents were unremarkable. The
      etiology and pathogenesis of this unique syndrome are unknown.

PMID- 24919764
TI  - A serendipitous identification of a lead extraction complication.
AB  - A 57-year-old male with a dual chamber pacemaker and symptomatic, persistent
      atrial fibrillation (AF) accompanying a febrile illness presented for elective
      transesophageal echocardiography (TEE)-guided cardioversion. The patient was
      found to have a large 2.5 cm * 2.3 cm, mobile mass attached to the right atrial
      lead. Following device and lead extraction, he developed progressive shortness of
      breath which was attributed to his underlying arrhythmia. One month later, AF
      ablation was pursued and preablation TEE revealed a dilated main pulmonary artery
      with a 1.8 cm * 1.6 cm mass in the distal left pulmonary artery, which was
      corroborated by a 1.4 cm * 2.5 cm filling defect in the descending left pulmonary
      artery on magnetic resonance angiography (MRA). To our knowledge, this is the
      first case report to document the distal migration of vegetation material into
      the pulmonary artery with serial TEE and highlights the risk of pulmonary
      embolism (PE) in patients with large endocardial lead vegetations undergoing
      transvenous lead extraction. 

PMID- 24919765
TI  - Richness and diversity in dust stormborne biomes at the southeast mediterranean.
AB  - Dust storms include particulate matter that is transported over land and sea with
      biota that could impact downwind ecosystems. In addition to the physico-chemical
      compositions, organismal diversities of dust from two storm events in southern
      Israel, December 2012 (Ev12) and January 2013 (Ev13), were determined by pyro
      sequencing using primers universal to 16S and 18S rRNA genes and compared. The
      bio-assemblages in the collected dust samples were affiliated with scores of
      different taxa. Distinct patterns of richness and diversity of the two events
      were influenced by the origins of the air masses: Ev13 was rich with reads
      affiliated to Betaproteobacteria and Embryophyta, consistent with a European
      origin. Ev12, originated in north-Africa, contained significantly more of the
      Actinobacteria and fungi, without conifers. The abundance of bacterial and
      eukaryotic reads demonstrates dissemination of biological material in dust that
      may impose health hazards of pathogens and allergens, and influence vegetation
      migration throughout the world. 

PMID- 24919766
TI  - Evaluation of the insulin-releasing and glucose-lowering effects of GPR120
      activation in pancreatic beta-cells.
AB  - AIMS: To assess the potency and selectivity of various GPR120 agonists and to
      determine the cellular localization of GPR120 in clonal beta-cells and pancreatic
      islets. METHODS: Insulin secretion and alterations in intracellular Ca(2+) and
      cAMP response to glucose and GPR120 agonists, including endogenous agonists alpha
      linolenic acid (ALA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and
      a synthetic analogue (GW-9508), were examined using clonal pancreatic BRIN-BD11
      cells, mouse pancreatic islets and in vivo studies using NIH Swiss mice.
      Cytotoxicity was assessed by lactate dehydrogenase release. Cellular localization
      of GPR120 was explored by double-staining immunohistochemistry. RESULTS: The most
      potent and selective GPR120 agonist tested was ALA (half maximum effective
      concentration 1.2 * 10(-8) mol/l) with a maximum stimulation of insulin secretion
      of 53% at 10(-4) mol/l (p < 0.001) in BRIN-BD11 cells. Stimulation of insulin
      secretion was also observed with GW-9508 (6.4 * 10(-8) mol/l; 47%), EPA (7.9 *
      10(-8) mol/l; 36%) and DHA (1.0 * 10(-7) mol/l; 50%). Results were corroborated
      by islet studies, with no evidence of cytotoxic effects. Dose-dependent insulin
      secretion by GPR120 agonists was glucose-sensitive and accompanied by significant
      elevations of intracellular Ca(2+) and cAMP. Immunocytochemistry showed GPR120
      expression on BRIN-BD11 cells and was confined to islet beta-cells with no
      distribution on alpha-cells. Administration of GPR120 agonists (0.1 umol/kg body
      weight) in glucose tolerance studies significantly reduced plasma glucose and
      augmented insulin release in mice. CONCLUSIONS: These results indicate that
      GPR120 is expressed on pancreatic beta-cells and that agonists at this receptor
      are potent insulin secretagogues with therapeutic potential for type 2 diabetes.

PMID- 24919767
TI  - Three-year trajectories of caregiver burden in Alzheimer's disease.
AB  - Although numerous studies have examined caregiver burden in the context of
      Alzheimer's disease, discrepancies remain regarding the influence of certain
      factors. This study aimed to identify trajectories of caregiver burden in the
      context of Alzheimer's disease, as well as the factors associated with them. A
      cohort of patients and caregivers (n = 330) was followed up over three years.
      Growth mixture models were fitted to identify trajectories of caregiver burden
      according to scores on the Zarit Burden Interview (ZBI). A multilevel multinomial
      regression analysis was then conducted with the resulting groups and the patient
      and caregiver factors. In the sample as a whole, burden increased during follow
      up (F = 4.4, p = 0.004). Three groups were identified: G1 (initially high but
      decreasing burden), G2 (moderate but increasing burden), and G3 (low burden that
      increased slightly). Patients in G1 and G2 presented more neuropsychiatric
      symptoms and poorer functional status than did those in G3. Caregivers in G1 and
      G2 had poorer mental health. Spouses and, especially, adult children who lived
      with their parent (the patient) were more likely to belong to G2 (odds ratio [OR]
      6.24; 95% CI 2.89-13.47), as were sole caregivers (OR 3.51; 95% CI 1.98-6.21).
      The patient factors associated with increased burden are neuropsychiatric
      symptoms and functional status, while among caregivers, being the sole carer,
      poor mental health, and living with the patient are of relevance. 

PMID- 24919768
TI  - Visuomotor impairments in older adults at increased Alzheimer's disease risk.
AB  - BACKGROUND AND OBJECTIVE: Recent evidence suggests that visuomotor behaviors may
      be disrupted in the very early stages of Alzheimer's disease (AD). Here we
      propose that using kinematic measures under conditions that place demands on
      visual-spatial and cognitive-motor processing may provide an effective behavioral
      means to detect subtle changes associated with AD risk. METHODS: To this end, we
      have tested 22 young adults (mean age = 26.4 +/- 4.1) and 22 older adults (mean
      age = 64.3 +/- 10.1) at low AD, and 22 older adults (mean age = 67.7 +/- 11.3) at
      high AD risk (i.e., strong family history or diagnosis of mild cognitive
      impairment). Kinematic measures were acquired on four visuomotor transformation
      tasks (standard, feedback reversal, plane dissociated, and plane dissociated +
      feedback reversal) using a dual-touchscreen tablet. RESULTS: Comparing
      participants at increased AD risk with both young and old healthy control groups
      revealed significant performance disruptions in at-risk individuals as task
      demands increased. Furthermore, we were able to discriminate between individuals
      at high and low AD risk with a classification accuracy of 86.4% (sensitivity:
      81.8%, specificity: 90.9%). CONCLUSION: We suggest that the impairments observed
      in individuals at increased AD risk may reflect inherent brain alteration and/or
      early neuropathology disrupting the reciprocal communication between hippocampal,
      parietal, and frontal brain regions required to successfully prepare and update
      complex reaching movements. Such impairment has the potential to affect
      activities of daily living, and may serve as a sensitive measure of functional
      ability in at-risk adults.

PMID- 24919769
TI  - Relationship between elevated morning blood pressure surge, uric acid, and
      cardiovascular outcomes in hypertensive patients.
AB  - Early morning blood pressure surge (MBPS) is a risk factor for cardiovascular
      events (CVEs), but the relationship with uric acid is not well understood. The
      authors aimed to determine the association between MBPS and increased uric acid
      and the effect of elevated MBPS and uric acid combination on CVEs. A total of 921
      patients underwent 24-hour ambulatory blood pressure monitoring and were followed
      for a median of 40 months. During this period, 103 (11.2%) CVEs occurred. There
      was a significant relationship between increasing quartiles of serum uric acid
      level and increasing values of MBPS (P<.0001). Patients in the highest quartile
      stratified by elevated MBPS and serum uric acid level had a 3.55 odds of major
      CVE compared with patients in the lowest quartile. Serum uric acid is associated
      with MBPS and development of new CVEs. 

PMID- 24919770
TI  - Apogossypolone, a small-molecule inhibitor of Bcl-2, induces radiosensitization
      of nasopharyngeal carcinoma cells by stimulating autophagy.
AB  - Nasopharyngeal carcinoma (NPC) is a major cause of cancer deaths. Concurrent
      administration of radiation and chemotherapy is the treatment of choice for
      advanced NPC. Previously, we showed that apogossypolone (ApoG2) induced apoptosis
      by blocking the binding of Bcl-2 to Bax, arresting the cell cycle in the S phase,
      in turn inhibiting proliferation of NPC cells both in vitro and in vivo. In the
      present study, we showed that ApoG2 inhibited the proliferation of NPC cells in a
      dose-dependent manner. We treated CNE1, CNE2 and SUNE1 cells with ApoG2 for 72 h,
      and calculated the IC50 values as 2.84, 5.64 and 2.18 uM, respectively. Normal
      NP69 cell proliferation was not significantly inhibited. ApoG2 treatment induced
      significant autophagy, demonstrated by an increase in LC3-II protein expression,
      reduced protein p62 expression, and accumulation of punctuate GFP-LC3 in the
      cytoplasm of CNE1 or CNE2 cells. Sh-Atg5 attenuated the autophagy induced by
      ApoG2, indicating that Atg5 was required for ApoG2-induced autophagy. In
      addition, ApoG2 treatment blocked the binding of Bcl-2 to Beclin 1 protein,
      releasing pro-autophagic Beclin 1, which in turn triggered the autophagic
      cascade. Colony formation assays indicated that ApoG2 enhanced radiosensitization
      of CNE2 cells. In the ApoG2-plus-radiation combination group, more ring-shaped
      structures were evident in CNE1 and CNE2 cultures. LC3-II expression was enhanced
      and that of p62 reduced, compared to the ApoG2-only, radiation-only and control
      groups. ApoG2 enhanced the radiosensitivity of CNE2 xenografts in nude mice as
      measured by (C-T)/C ratios (as percentages); the values for the ApoG2 and
      radiation groups were 46.89% and 19.34%, respectively. The ApoG2-plus-radiation
      group exhibited greater antitumor activity (the inhibitory rate was 61.64%).
      Immunohistological staining showed that LC3-II expression became gradually
      upregulated in the ApoG2-plus-radiation group. Together, the results suggest that
      ApoG2 inhibits the binding of Bcl-2 to Beclin 1, inducing autophagy and radio
      sensitizing NPC cells both in vitro and in vivo.

PMID- 24919772
TI  - The impact of anion electronic structure: similarities and differences in
      imidazolium based ionic liquids.
AB  - In this paper the structural and energetic landscapes of ion-pair dimer
      conformers of 1,3-dimethylimidazolium based ionic liquids have been explored
      ([C1C1im][A])2, A = Cl(-), [NO3](-), [MeSO4](-), [OTf](-) and [BF4](-)). A common
      low-energy conformer has been selected for full electronic structure analysis. We
      have compared and contrasted each cluster based on the relative hydrogen bonding
      ability (beta-value) of the anion, which varies experimentally as Cl(-) > [NO3](
      ) ~ [MeSO4](-) > [OTf](-) ~ [BF4](-). Correlations between experimental beta
      values, computed binding energies, charge transfer and various hydrogen bonding
      data have been made and outliers have been explained in terms of environmental
      effects present in the liquid phase. This is most evident in the structurally
      similar [MeSO4](-) and [OTf](-) anions that have very similar hydrogen bonding
      motifs, but significantly different beta-values. Moreover, detailed analysis of
      the cluster molecular orbitals, for each anion, reveals a subtle interplay
      between two modes of interaction, an in-plane traditional H-bonding and inter
      planar anion-pi interaction. Inter-planar anion-pi interactions are particularly
      prominent for the [NO3](-) cluster. We have rationalized how the full range of
      interactions could impact on the structuring of ILs at surfaces and the effect
      these may have on viscosity. 

PMID- 24919771
TI  - Options for tracking GFP-Labeled transplanted myoblasts using in vivo
      fluorescence imaging: implications for tracking stem cell fate.
AB  - BACKGROUND: Green fluorescent protein (GFP) is a useful biomarker, widely used in
      biomedical research to track stem cells after transplantation and/or to assess
      therapeutic transgene expression. However, both GFP and therapeutic gene products
      themselves may be immunogenic to the recipient. The main aim of this study was to
      use animal models to evaluate potential impact of GFP on the cell engraftment and
      to optimize tracking strategies prior to transplantation. RESULTS: By using a
      fluorescent imaging (FLI) system, we investigated the dynamic cell behavior of
      GFP-transduced myoblasts in tibialis anterior (TA) muscles of immunocompetent mdx
      mice and immuno-compromised nude mice over a period of three months. The results
      suggested an apparent underlying host immunorejection in the mdx mice. Dystrophin
      immunostaining showed that the engraftment of wild type myoblasts was much more
      effective than that of the GFP-labeled counterparts in the mdx mice, further
      confirming an antigen role of GFP in this process. We tracked the GFP-transduced
      myoblasts in C57BL/6 mice and found GFP to be minimally immunogenic in these
      animals, as indicated by the GFP signal maintaining a much stronger level than
      that found in mdx and BALB/c mice at parallel time points. We also compared the
      in vivo cell behavior differences between myoblasts from virally GFP-transduced
      and GFP transgenic mice. The latter displayed much better engraftment, as
      determined both biomaging and histological observations. CONCLUSIONS: Our results
      not only demonstrated the immunogenicity of GFP in immunocompetent mice, but
      determined the optimized conditions for GFP-based in vivo stem cells tracking,
      that can potentially be extrapolated to human biomedical research.

PMID- 24919773
TI  - Mitochondrial DNA phylogeography of the Labeobarbus intermedius complex (Pisces,
      Cyprinidae) from Ethiopia.
AB  - Mitochondrial DNA phylogeography of populations of the Labeobarbus intermedius
      complex (hexaploid barb) was investigated using 88 complete and 71 partial
      cytochrome b (cytb) sequences originating from 21 localities in five major
      drainages in Ethiopia and two localities in northern Kenya. The samples included
      14 of the 15 Labeobarbus species described from Lake Tana. Discrete
      phylogeographic analyses of 159 cytb sequences employing Bayesian Markov Chain
      Monte Carlo (MCMC) simulations using Bayesian evolutionary analysis by sampling
      trees (BEAST) supported the monophyly of the L. intermedius complex, including
      the Lake Tana species. This analysis, in combination with statistical parsimony
      analysis, identified two mitochondrial DNA lineages within the complex.
      Divergence dating employing coalescent simulations suggested that the geographic
      split in the L. intermedius complex that led to the formation of these lineages
      occurred during the Pleistocene (c. 0.5 M b.p.), consistent with the timing of
      volcano-tectonic events postulated to have shaped the current landscape of East
      Africa.

PMID- 24919774
TI  - Cervical necrotizing fasciitis of nonodontogenic origin: case report and review
      of literature.
AB  - Cervical necrotizing fasciitis (CNF) is a potentially fatal infection
      characterized by generalized necrosis of the cervical fascia that progresses
      rapidly. The incidence of this entity corresponds to 2.6% of all infections of
      the head and neck. The most frequent primary origin is dental infection, although
      other causes exist that should be evaluated.Delay in the diagnosis of this entity
      may lead to rapid progression and fatal outcome. Patients often present
      immunosuppression or systemic diseases that predispose them to this pathology.
      Cervical necrotizing fasciitis is associated with mortality rates of 7% to 20%
      depending on the extension of the cervical lesion. The highest rates correspond
      to cases that progress to mediastinitis or septic shock, which are the main and
      most frequent complications. Early detection and adequate emergency treatment are
      critical in the management of these patients and may reduce morbimortality and
      improve survival. The emergency services should be prepared to manage such cases
      efficiently, through a multidisciplinary treatment by coordinating emergency
      surgery with critical support and clinical stabilization of patients.We present a
      case of CNF of non odontogenic origin managed in our hospital.

PMID- 24919775
TI  - Frequent attenders to the ED: patients who present with repeated asthma
      exacerbations.
AB  - BACKGROUND: Asthma has been reported as one of the main causes of frequent
      attendance to the emergency department (ED), and many of those visits are
      potentially preventable. Understanding the characteristics of frequent attender
      (FA) patients with asthmatic exacerbations will help to identify factors
      associated with frequent attendance and improve case management. The aim of this
      study is to describe the characteristics of FA who present multiple times to the
      ED for asthma exacerbations. METHODS: This study was a retrospective review of
      cases presented to Singapore General Hospital ED in 2010. Patients who attended
      the ED for 4 times or more with at least 1 visit attributable to asthma
      exacerbations in 2010 were included. They were then categorized as FA with
      multiple exacerbations (FAME) and those with fewer exacerbations. RESULTS: Of
      105616 ED patients, 155 patients attending the ED in 2010 were identified as FA
      with asthma, and 26 (17%) of these patients were classified as FAME, resulting in
      213 visits (45% of total visits). Compared with FA with fewer exacerbations
      group, FAME were more likely to be men (P = .002), unemployed (P < .000), bad
      debtors (P = .045), substance abusers (P = .022), previously known to medical
      social workers (P = .002), and were found to spend a longer amount of time in the
      ED (>6 hours) (P = .03). CONCLUSION: We found that a small number of FAME
      patients accumulated a large number of ED visits and spent a significantly longer
      time in the ED. This group tended to be males with social, financial, and
      addiction problems.

PMID- 24919776
TI  - Osteoclasts and their precursors are present in the induced-membrane during bone
      reconstruction using the Masquelet technique.
AB  - In 2000, Masquelet reported a long bone reconstruction technique using an induced
      membrane formed around a polymethylmethacrylate (PMMA) spacer placed in the
      defect with appropriate stabilization followed by secondary bone graft after PMMA
      removal. This reconstruction procedure allows rapid and safe bone reformation for
      septic, traumatic, neoplastic or congenital bone defects. A rat model of the
      Masquelet technique was developed to further characterize the biological
      activities of this induced membrane. Our model allows healing of a critical-sized
      femoral defect (8 mm) by means of this procedure over a period of 18 weeks.
      Comparison of induced membranes obtained 3, 4, 5 and 6 weeks after PMMA insertion
      indicated that this tissue changes over time. Several mineralization spots and
      bone cells were observed in contact with the PMMA, when assessed by Alizarin Red,
      Von Kossa, Alkaline phosphatase and Tartrate-resistant acid phosphatase staining
      of the membranes. CTR (calcitonin receptor)- and RANK (Receptor Activator of
      Nuclear factor Kappa B)- positive mononuclear cells were detected in the induced
      membrane, confirming the presence of osteoclasts in this tissue. These cells were
      observed in a thin, highly cellular layer in the induced membrane in contact with
      the PMMA. Together, these findings suggest that the membrane is able to promote
      osteointegration of autologous corticocancellous bone grafts during the Masquelet
      technique by creating local conditions that may be favourable to graft bone
      remodelling and osteointegration. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24919777
TI  - Gold(III) compounds containing a chelating, dicarbanionic ligand derived from
      4,4'-di-tert-butylbiphenyl.
AB  - An oligomeric gold(III) compound containing dicarbanionic chelating 4,4'-di-tert
      butylbiphenyl was prepared via transmetallation using the corresponding
      organotin(IV) compound. The reactivity of the chloro-bridged oligomer with
      various species including neutral N-, P-, and C-donor ligands as well as
      monoanionic S- and Se-ligands was investigated. Some of the products were
      characterised by X-ray crystallography. The photophysical properties of two
      derivatives were studied.

PMID- 24919779
TI  - The Work-Family Conflict Scale (WAFCS): development and initial validation of a
      self-report measure of work-family conflict for use with parents.
AB  - This paper outlines the development and validation of the Work-Family Conflict
      Scale (WAFCS) designed to measure work-to-family conflict (WFC) and family-to
      work conflict (FWC) for use with parents of young children. An expert informant
      and consumer feedback approach was utilised to develop and refine 20 items, which
      were subjected to a rigorous validation process using two separate samples of
      parents of 2-12 year old children (n = 305 and n = 264). As a result of
      statistical analyses several items were dropped resulting in a brief 10-item
      scale comprising two subscales assessing theoretically distinct but related
      constructs: FWC (five items) and WFC (five items). Analyses revealed both
      subscales have good internal consistency, construct validity as well as
      concurrent and predictive validity. The results indicate the WAFCS is a promising
      brief measure for the assessment of work-family conflict in parents. Benefits of
      the measure as well as potential uses are discussed.

PMID- 24919778
TI  - Improved virologic outcomes over time for HIV-infected patients on antiretroviral
      therapy in a cohort from Rio de Janeiro, 1997-2011.
AB  - BACKGROUND: Previous cohort studies have demonstrated the beneficial effects of
      antiretroviral therapy (ART) on viral load suppression. We aimed to examine the
      factors associated with virologic suppression for HIV-infected patients on ART
      receiving care at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz
      Foundation in Rio de Janeiro, Brazil. METHODS: HIV-1 RNA levels and CD4+ T-cell
      counts at the date closest to midyear (1 July) were evaluated for 1,678 ART-naive
      patients >= 18 years of age initiating ART between 1997 and 2010. The odds ratios
      (OR) and 95% confidence intervals (CI) for having an undetectable viral load (<=
      400 copies/mL) were estimated using generalized estimating equations regression
      models adjusted for clinical and demographic factors. Time-updated covariates
      included age, years since HIV diagnosis, hepatitis C diagnosis and ART
      interruptions. RESULTS: Between 1997 and 2011, the proportion of patients with an
      undetectable viral load increased from 6% to 78% and the median [interquartile
      range] CD4+ T-cell count increased from 207 [162, 343] to 554 [382, 743]
      cells/MUL. Pre-treatment median CD4+ T-cell count significantly increased over
      the observation period from 114 [37, 161] to 237 [76, 333] cells/MUL (p < .001).
      The per-year adjusted OR (aOR) for having undetectable viral load was 1.18 (95%
      CI = 1.16-1.21). ART interruptions >1 month per calendar significantly decreased
      the odds [aOR = 0.32 (95% CI = 0.27-0.38)] of having an undetectable viral load.
      Patients initiating on a protease inhibitor (PI)-based first-line regimen were
      less likely to have undetectable viral load [aOR = 0.72 (95% CI = 0.63-0.83)]
      compared to those initiating on a non-nucleoside reverse transcriptase inhibitor
      (NNRTI)-based regimen. CONCLUSIONS: Our results demonstrate significant
      improvements in virologic outcomes from 1997 to 2011, which persisted after
      adjusting for other factors. This may in part be due to improvements in care and
      new treatment options. NNRTI- versus PI-based first-line regimens were found to
      be associated with increased odds of having an undetectable viral load,
      consistent with previous studies. Treatment interruptions were found to be the
      most important determinant of not having an undetectable viral load. Studies are
      needed to characterize the reasons for treatment interruptions and to develop
      subsequent strategies for improving adherence to ART.

PMID- 24919780
TI  - Maximum noble-metal efficiency in catalytic materials: atomically dispersed
      surface platinum.
AB  - Platinum is the most versatile element in catalysis, but it is rare and its high
      price limits large-scale applications, for example in fuel-cell technology.
      Still, conventional catalysts use only a small fraction of the Pt content, that
      is, those atoms located at the catalyst's surface. To maximize the noble-metal
      efficiency, the precious metal should be atomically dispersed and exclusively
      located within the outermost surface layer of the material. Such atomically
      dispersed Pt surface species can indeed be prepared with exceptionally high
      stability. Using DFT calculations we identify a specific structural element, a
      ceria "nanopocket", which binds Pt(2+) so strongly that it withstands sintering
      and bulk diffusion. On model catalysts we experimentally confirm the
      theoretically predicted stability, and on real Pt-CeO2 nanocomposites showing
      high Pt efficiency in fuel-cell catalysis we also identify these anchoring sites.

PMID- 24919781
TI  - Dislocated dental bridge covering the larynx: usefulness of tracheal tube guides
      under video-assisted laryngoscopy for induction of general anesthesia, thus
      avoiding tracheostomy.
AB  - BACKGROUND: To describe a case with dislodgement of dental bridge with clasps
      covering the vocal cords, in a patient who was successfully intubated using tube
      exchanger under video-assisted laryngoscopy. STUDY DESIGN, METHODS: Clinical case
      record with a video clip. SETTING: University hospital. CASE PRESENTATION: A 83
      year-old woman presented with dislodgement of her dental bridge whilst eating.
      Laryngoscopy revealed a foreign body almost entirely covering the vocal cords,
      with the clasps of the dislodged partial denture piercing the pharyngeal wall.
      Before induction of general anesthesia, a tracheal tube introducer combined with
      video-assisted laryngoscopy was introduced into the trachea in the awake
      condition, followed by successful endotracheal intubation. Thereafter, the
      dislodged denture was extracted via the oral cavity. CONCLUSIONS: Tracheal tube
      introducers combined with video-assisted laryngoscopy appear to be useful for
      airway management, decreasing the number of avoidable tracheostomies performed.

PMID- 24919782
TI  - The assessment of relationship between left ventricular geometry and microvolt T
      wave alternans in sustained hypertension.
AB  - OBJECTIVE: Left ventricular (LV) hypertrophy (LVH) predicts increased mortality
      in part due to an elevated incidence of sudden cardiac death in hypertension. The
      aim of the present study was to investigate the relation of microvolt T-wave
      alternans (MTWA) with different LV geometric patterns in patient with sustained
      hypertension. METHODS: This study consisted of 311 consecutive patients with
      sustained hypertension who were divided into four groups according to LV
      geometrical patterns. 90 patients were in the normal geometry group (NGG) [mean
      age 49.6 +/- 7.8 years; 60 males (66.7%)], 99 patients were in the concentric
      remodeling group (CRG) [mean age 50.9 +/- 6.6 years; 50 males (50.6%)], 63
      patients were in the concentric hypertrophy group (CHG) [mean age 51.6 +/- 7.3
      years; 32 males (50.7%)] and 58 patients were in the eccentric hypertrophy group
      (EHG) [mean age 51.6 +/- 9.0 years; 30 males (51.7%)]. Physical examination,
      laboratory work-up, office blood pressure measurement, transthoracic
      echocardiography and MTWA measurements were performed on all participants.
      RESULTS: MTWA positivity was significantly higher in EHG and CHG as compared to
      CRG and NGG (p < 0.001). Left ventricle mass index (LVMI), LV end-diastolic
      diameter (LVEDD), LV end-systolic diameter (LVESD), interventricular septum
      diameter (IVSd), posterior wall diameter (PWd) and office systolic blood pressure
      (SBP) were found to be significantly positively correlated with MTWA (all p
      values < 0.05). CONCLUSION: We demonstrated that increased LVMI is associated
      with an elevated MTWA positivity in sustained hypertensives. Moreover, clinically
      significant LV geometric patterns including both concentric and eccentric
      hypertrophy are related with a raised MTWA positivity, which may lead to
      particular predilection to life-threatening ventricular arrhythmias and sudden
      cardiac death in sustained hypertension.

PMID- 24919783
TI  - Why Dutch general practitioners do not put the squeeze on access to hospital
      care?

PMID- 24919784
TI  - Mechanosensing of cells in 3D gel matrices based on natural and synthetic
      materials.
AB  - Cells in vivo typically are found in 3D matrices, the mechanical stiffness of
      which is important to the cell and tissue-scale biological processes. Although it
      is well characterized that as to how cells sense matrix stiffness in 2D
      substrates, the scenario in 3D matrices needs to be explored. Thus, materials
      that can mimic native 3D environments and possess wide, physiologically relevant
      elasticity are highly desirable. Natural polymer-based materials and synthetic
      hydrogels could provide an better 3D platforms to investigate the mechano
      response of cells with stiffness comparable to their native environments.
      However, the limited stiffness range together with interdependence of matrix
      stiffness and adhesive ligand density are inherent in many kinds of materials,
      and hinder efforts to demonstrate the true effects contributed by matrix
      stiffness. These problems have been addressed by the recently emerging
      exquisitely designed materials based on native matrix components, designer
      matrices, and synthetic polymers. In this review, a variety of materials with a
      wide stiffness range that mimic the mechanical environment of native 3D matrices
      and the independent affection of stiffness for cellular behavior and tissue-level
      processes are discussed. 

PMID- 24919786
TI  - Systemic lupus erythematosus complicating simple silicosis.
AB  - Inhalation of crystalline silica is known to result in silicosis: an
      irreversible, disabling and potentially fatal occupational lung disease, which is
      associated with a variety of pulmonary and non-pulmonary complications including
      autoimmunity. A potential link between silicosis and systemic lupus erythematosus
      (SLE) is currently recognized only in cases of acute or accelerated silicosis. We
      report a case of SLE, a disease which usually affects young females, arising in a
      male former stonemason with simple silicosis. Epidemiological and clinical
      literature on the association of silica exposure and development of SLE are
      briefly reviewed. This case report and literature review highlight the link
      between occupational silica exposure and autoimmune disease including SLE,
      establishes that even simple silicosis appears linked to development of
      autoimmunity and emphasizes the importance of an occupational history, especially
      in male patients who develop SLE. 

PMID- 24919785
TI  - Systematic examination of the fetal abdominal precordial veins: a cohort study.
AB  - OBJECTIVES: Examination of the fetal venous system is a necessary part of
      complete fetal organ scanning to confirm landmark anatomy, such as the ductus
      venosus and course of the umbilical veins, and, whenever cardiovascular anomalies
      are identified, to exclude associated anomalous development of the fetal veins.
      We aimed to develop a protocol for systematic examination of the fetal venous
      system during midtrimester targeted organ scanning. METHODS: We included low-risk
      women with a singleton fetus presenting between January 2011 and June 2013 to our
      center for routine midtrimester (20-24 weeks) targeted organ scanning. Imaging of
      the venous system was added to the booked scan and comprised two-dimensional
      color Doppler scanning of the fetal abdomen in three discrete planes, two
      transverse and one longitudinal. The more caudal plane was obtained in a ventral
      or lateral transverse abdominal plane to image the umbilical vein, left portal
      vein, portal sinus, anterior right portal vein, posterior right portal vein, main
      portal vein and splenic vein and artery. Moving cephalad, a ventral or lateral
      transverse plane was obtained to image the right, middle and left hepatic veins
      and inferior vena cava (IVC). Finally, a longitudinal anteroposterior plane
      showed the umbilical vein, ductus venosus, IVC and left hepatic vein. In some
      cases the pulsed Doppler waveform of a given target vessel was also examined.
      Three-dimensional/4D ultrasound was applied as necessary, when anomalous cases
      were encountered. RESULTS: We examined 1810 women. Their body mass index ranged
      from 19 to 40 (mean, 24.7). In 38 (2.1%) women, the target anatomy was not
      visualized satisfactorily owing to maternal body habitus. A T-shaped
      configuration of the portal system vessels was observed in 63% of cases, an X
      shaped configuration in 25% and an H-shaped configuration in 12%. During the
      study period, 24 congenital anomalies of the precordial venous system were
      diagnosed: nine cases of persistent right umbilical vein, seven of agenesis of
      the ductus venosus, five of anomalous portal venous drainage and three of
      interrupted IVC with azygos continuation. CONCLUSIONS: Examination of the fetal
      venous system is feasible with the application of three abdominal planes. While a
      venous system scan is not practicable as part of a screening-level examination,
      mastery of the normal anatomy is an essential part of the professional knowledge
      base, in order to provide ready and complete scanning of the system in cases of
      suspected anomalies or disordered cardiac function.

PMID- 24919787
TI  - Surface modification of coronary stents with SiCOH plasma nanocoatings for
      improving endothelialization and anticoagulation.
AB  - The surface properties of intravascular stent play a crucial role in preventing
      in-stent restenosis (ISR). In this study, SiCOH plasma nanocoatings were used to
      modify the surfaces of intravascular stents to improve their endothelialization
      and anticoagulation properties. SiCOH plasma nanocoatings with thickness of 30-40
      nm were deposited by low-temperature plasmas from a gas mixture of trimethysilane
      (TMS) and oxygen at different TMS:O2 ratios. Water contact angle measurements
      showed that the SiCOH plasma nanocoating surfaces prepared from TMS:O2  = 1:4 are
      hydrophilic with contact angle of 29.5 +/- 1.9 degrees . The SiCOH plasma
      nanocoated 316L stainless steel (316L SS) wafers were first characterized by in
      vitro adhesion tests for blood platelets and human umbilical vein endothelial
      cells. The in vitro test results showed that the SiCOH plasma nanocoatings
      prepared from TMS:O2  = 1:4 had excellent hemo- and cytocompatibility. With
      uncoated 316L SS stents as the control, the SiCOH plasma nanocoated 316L SS
      stents were implanted into rabbit abdominal artery model for in vivo evaluation
      of re-endothelialization and ISR inhibition. After implantation for 12 weeks, the
      animals testing results showed that the SiCOH plasma nanocoatings accelerated re
      endothelialization and inhibited ISR with lumen reduction of 26.3 +/- 10.1%,
      which were considerably less than the 41.9 +/- 11.6% lumen reduction from the
      uncoated control group.

PMID- 24919788
TI  - Effects of functional feeds on the lipid composition, transcriptomic responses
      and pathology in heart of Atlantic salmon (Salmo salar L.) before and after
      experimental challenge with Piscine Myocarditis Virus (PMCV).
AB  - BACKGROUND: Cardiomyopathy syndrome (CMS) is a severe cardiac disease of Atlantic
      salmon (Salmo salar) recently associated with a double-stranded RNA virus,
      Piscine Myocarditis Virus (PMCV). The disease has been diagnosed in 75-85 farms
      in Norway each year over the last decade resulting in annual economic losses
      estimated at up to ?9 million. Recently, we demonstrated that functional feeds
      led to a milder inflammatory response and reduced severity of heart lesions in
      salmon experimentally infected with Atlantic salmon reovirus, the causal agent of
      heart and skeletal muscle inflammation (HSMI). In the present study we employed a
      similar strategy to investigate the effects of functional feeds, with reduced
      lipid content and increased eicosapentaenoic acid levels, in controlling CMS in
      salmon after experimental infection with PMCV. RESULTS: Hepatic steatosis
      associated with CMS was significantly reduced over the time course of the
      infection in fish fed the functional feeds. Significant differences in immune and
      inflammatory responses and pathology in heart tissue were found in fish fed the
      different dietary treatments over the course of the infection. Specifically, fish
      fed the functional feeds showed a milder and delayed inflammatory response and,
      consequently, less severity of heart lesions at earlier and later stages after
      infection with PMCV. Decreasing levels of phosphatidylinositol in cell membranes
      combined with the increased expression of genes related with T-cell signalling
      pathways revealed new interactions between dietary lipid composition and the
      immune response in fish during viral infection. Dietary histidine supplementation
      did not significantly affect immune responses or levels of heart lesions.
      CONCLUSIONS: Combined with the previous findings on HSMI, the results of the
      present study highlight the potential role of clinical nutrition in controlling
      inflammatory diseases in Atlantic salmon. In particular, dietary lipid content
      and fatty acid composition may have important immune-modulatory effects in
      Atlantic salmon that could be potentially beneficial in fish balancing the immune
      and tissue responses to viral infections.

PMID- 24919789
TI  - Impact of heparin-induced thrombocytopenia on acute coronary artery thrombosis in
      patients undergoing PCI.

PMID- 24919791
TI  - Near-peer teaching (NPT): the importance of process evaluation.

PMID- 24919792
TI  - Studies toward the total synthesis of pluraflavin A.
AB  - A synthetic strategy towards the potent cytostatic agent pluraflavin A has been
      developed. Formation of the enantioenriched anthrapyran core bearing a halogen
      atom enabled the introduction of the alpha C-aryl glycoside by Stille cross
      coupling and subsequent hydrogenation of the aryl glycal. Chemo- and
      stereoselective O-glycosylations of alpha oliose and beta 3-epi vancosamine
      residues afforded a fully glycosylated aromatic core. Attempts to install the
      dimethylamino group of the C-disaccharide suggest that introduction of an azide
      group by displacement and subsequent reduction may pave the way to the total
      synthesis of pluraflavin A. 

PMID- 24919790
TI  - Presynaptic dopaminergic function: implications for understanding treatment
      response in psychosis.
AB  - All current antipsychotic drugs block dopamine (DA) receptors, but the nature of
      the DA dysfunction in schizophrenia has not been clear. However, consistent
      evidence now shows that presynaptic dopaminergic function is altered in
      schizophrenia, specifically in terms of increased DA synthesis capacity, baseline
      synaptic DA levels, and DA release. Furthermore, presynaptic dopaminergic
      function is already elevated in prodromal patients who later developed the
      disorder. Currently available antipsychotics act on postsynaptic receptors, not
      targeting presynaptic DA abnormalities. This has implications for understanding
      response and developing new treatments. The lack of normalization of the abnormal
      presynaptic function could explain why discontinuation is likely to lead to
      relapse, because the major dopaminergic function persists, meaning that once
      treatment stops there is nothing to oppose the dysregulated dopamine function
      reinstating symptoms. Furthermore, it suggests that drugs that target presynaptic
      dopaminergic function may constitute new treatment possibilities for
      schizophrenic patients, in particular, for those in whom antipsychotics are
      poorly effective. In addition, the longitudinal changes with the onset of
      psychosis indicate the potential to target a defined dynamic neurochemical
      abnormality to prevent the onset of psychosis. 

PMID- 24919793
TI  - Likelihood ratio based tests for longitudinal drug safety data.
AB  - This article presents longitudinal likelihood ratio test (LongLRT) methods for
      large databases with exposure information. These methods are applied to a pooled
      large longitudinal clinical trial dataset for drugs treating osteoporosis with
      concomitant use of proton pump inhibitors (PPIs). When the interest is in the
      evaluation of a signal of an adverse event for a particular drug compared with
      placebo or a comparator, the special case of the LongLRT, referred to as
      sequential LRT (SeqLRT), is also presented. The results show that there is some
      possible evidence of concomitant use of PPIs leading to more adverse events
      associated with osteoporosis. The performance of the proposed LongLRT and SeqLRT
      methods is evaluated using simulated datasets and shown to be good in terms of
      (conditional) power and control of type I error over time. The proposed methods
      can also be applied to large observational databases with exposure information
      under the US Food and Drug Administration Sentinel Initiative for active
      surveillance. Published 2014. This article is a US Government work and is in the
      public domain in the USA. 

PMID- 24919794
TI  - Quinazoline analog HMJ-30 inhibits angiogenesis: involvement of endothelial cell
      apoptosis through ROS-JNK-mediated death receptor 5 signaling.
AB  - The aim of the present study was to explore the effect of 6-fluoro-2-(3
      fluorophenyl)-4-(cyanoanilino) quinazoline (HMJ-30) on the anti-angiogenic
      properties and apoptosis-related mechanism of human umbilical vein endothelial
      cells (HUVECs). In this study, HMJ-30 dose- and time-dependently inhibited the
      viability of HUVECs. We also found that HMJ-30 enhanced disruption of tube-like
      structures and suppressed cell migration in HUVECs after vascular endothelial
      growth factor (VEGF) induction. HMJ-30 was also observed to inhibit vessel
      branching and sprouting in chicken chorioallantoic membrane (CAM). Microsprouting
      induced by VEGF in the rat aortic ring and blood vessel formation in a mouse
      Matrigel plug were individually suppressed by HMJ-30. In an in vitro study, HMJ
      30 induced the apoptotic death of HUVECs as indicated by DNA fragmentation and
      promoted reactive oxygen species (ROS) production as determined by flow
      cytometric assay. In addition, extrinsic caspase signaling (caspase-8 and -3) was
      activated in the HMJ-30-treated HUVECs and their inhibitors were applied to
      assess the signal transduction. We investigated the upstream of the death
      receptor pathway and further observed that the levels of death receptor 5 (DR5)
      and phosphorylated c-Jun N-terminal kinase (JNK) signals were upregulated in
      HUVECs following HMJ-30 challenge, which was confirmed by a JNK-specific
      inhibitor (SP600125). Hence, HMJ-30-induced endothelial cell apoptosis involved
      the ROS/JNK-regulated DR5 pathway. In summary, HMJ-30 may provide a potential
      therapeutic effect for the anti-vascular targeting of angiogenesis during cancer
      treatment.

PMID- 24919796
TI  - Neanderthal infant and adult infracranial remains from Marillac (Charente,
      France).
AB  - At the site of Marillac, near the Ligonne River in Marillac-le-Franc (Charente,
      France), a remarkable stratigraphic sequence has yielded a wealth of
      archaeological information, palaeoenvironmental data, as well as faunal and human
      remains. Marillac must have been a sinkhole used by Neanderthal groups as a
      hunting camp during MIS 4 (TL date 57,600 +/- 4,600BP), where Quina Mousterian
      lithics and fragmented bones of reindeer predominate. This article describes
      three infracranial skeleton fragments. Two of them are from adults and consist of
      the incomplete shafts of a right radius (Marillac 24) and a left fibula (Marillac
      26). The third fragment is the diaphysis of the right femur of an immature
      individual (Marillac 25), the size and shape of which resembles those from Teshik
      Tash and could be assigned to a child of a similar age. The three fossils have
      been compared with the remains of other Neanderthals or anatomically Modern
      Humans (AMH). Furthermore, the comparison of the infantile femora, Marillac 25
      and Teshik-Tash, with the remains of several European children from the early
      Middle Ages clearly demonstrates the robustness and rounded shape of both
      Neanderthal diaphyses. Evidence of peri-mortem manipulations have been identified
      on all three bones, with spiral fractures, percussion pits and, in the case of
      the radius and femur, unquestionable cutmarks made with flint implements,
      probably during defleshing. Traces of periostosis appear on the fibula fragment
      and on the immature femoral diaphysis, although their aetiology remains unknown.

PMID- 24919797
TI  - Dominant behaviours in the expression of human carbonic anhydrase hCA I activity.
AB  - Here we describe the screening via Dynamic Deconvolution of DCLs of inhibitors
      (CAIs) and activators (CAAs) of hCA I. The inhibitory effects dominate over the
      activating ones, while the CAAs may be identified in the absence of CAIs. 

PMID- 24919798
TI  - Determination of 3-monochloropropane-1,2-diol fatty acid esters in Brazilian
      vegetable oils and fats by an in-house validated method.
AB  - An in-house validated GC-MS method preceded by acid-catalysed methanolysis was
      applied to 97 samples of vegetable oils and fats marketed in Brazil. The levels
      of the compounds ranged from not detected (limit of detection = 0.05 mg kg(-1))
      to 5.09 mg kg(-1), and the highest concentrations were observed in samples
      containing olive pomace oil and in products used for industrial applications,
      such as palm oil and its fractions (olein and stearin). The content of diesters
      and monoesters was also investigated by employing solid-phase extraction on
      silica cartridges, indicating that the majority of the compounds were present as
      diesters. This study provides the first occurrence data on these contaminants in
      Brazil and the results are comparable with those reported in other countries. 

PMID- 24919799
TI  - Efficacy of a needling device for the treatment of acne scars: a randomized
      clinical trial.
AB  - IMPORTANCE: Neocollagenesis can be achieved using a dermal rolling needle device,
      thereby reducing the appearance of acne scars. OBJECTIVE: To determine the
      efficacy of a needling device for treatment of acne scars. DESIGN, SETTING, AND
      PARTICIPANTS: We performed a single-center, rater-blinded, balanced (1:1), split
      face, placebo-controlled, parallel-group randomized clinical trial at an urban
      academic institution. The study took place from November 30, 2009, through July
      27, 2010. Twenty healthy adults (age range, 20-65 years) with acne scars on both
      sides of the face were enrolled. Fifteen individuals completed the study, and no
      enrolled participants were withdrawn for adverse effects. INTERVENTIONS: For each
      participant, one side of the face was randomized for needling. Three needling
      treatments were performed at 2-week intervals. MAIN OUTCOMES AND MEASURES: Two
      blinded dermatologists separately rated participants' acne scars based on
      standard digital photographs obtained at baseline and at the 3-month and 6-month
      follow-up visits on the quantitative global scarring grading system. RESULTS:
      Mean scar scores were significantly lower in the treatment group compared with
      baseline at 6 months (mean difference, 3.4; 95% CI, 0.2-6.5; P = .03) and
      nominally but not significantly lower compared with baseline at 3 months (mean
      difference, 2.4; 95% CI, -0.01 to 4.8; P = .052). In the control group, mean scar
      scores did not vary significantly from baseline at 3 months (mean difference,
      1.0; 95% CI, -1.4 to 3.4; P = .96) and at 6 months (mean difference, 0.4; 95% CI,
      -2.3 to 3.5; P > .99). The needling procedure was not particularly painful, with
      a mean pain rating of 1.08 of 10. Participants perceived a 41% mean improvement
      in overall scar appearance on the treated side. No adverse events were reported.
      CONCLUSIONS AND RELEVANCE: After 3 needling treatments, there was improvement in
      the appearance of acne scars over time compared with the control group, with
      minimal pain reported. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00974870.

PMID- 24919800
TI  - Surgical treatment of intraparenchymal hemorrhage during mechanical circulatory
      support for heart-failure--a single-centre experience.
AB  - BACKGROUND: Cranial intraparenchymal hemorrhage represents a critical
      complication of mechanical circulatory support requiring constant antithrombotic
      treatment. Surgery of intraparenchymal hemorrhage under anticoagulation
      represents a challenge and imposes significant risks for patients. It was the aim
      to analyse surgical and clinical outcome of patients requiring surgical treatment
      due to intraparenchymal hemorrhage. METHODS: Patients with mechanical circulatory
      support requiring surgical therapy due to space-occupying lobar supratentorial or
      infratentorial hemorrhage from January 1, 2009 to January 1, 2014 were included
      in our study. Baseline parameters are preoperative International Normalized Ratio
      (INR) values, postoperative anticoagulation regiment, bleeding size and
      localization. Co-primary outcome parameters were the extent of hematoma
      evacuation and the Modified Rankin Scale at discharge from hospital. Secondary
      outcome parameters included rate of recurrent hemorrhage, rate of revision
      surgery and in-hospital mortality. RESULTS: Twelve patients (mean age 44 +/- 18
      years, nine supratentorial-/three infratentorial hemorrhages, 11 left ventricular
      assist devices, and one extracorporeal membrane oxygenation) were included.
      Surgical hematoma evacuation was performed in 11 patients, one patient received
      decompressive hemicraniectomy. Hematoma evacuation was complete in no patients,
      and partial in 11 patients. Initial INR was 2,7 +/- 1,6. Rate of recurrent
      hemorrhage was 75 %. Revision surgery was performed in three patients achieving
      partial hematoma evacuation in two patients and complete evacuation in one
      patient. Modified Rankin Scale at discharge from hospital was six in nine
      patients (in-hospital mortality of 75 %), five in two patients and four in one
      patient. CONCLUSIONS: Surgical treatment of life threatening, space-occupying
      intraparenchymal hemorrhage under mechanical circulation support is of limited
      efficacy with high rates of recurrent hemorrhage and in-hospital mortality. We
      provide additional data that postponing anticoagulation is feasible and may lead
      to improved clinical outcome and survival.

PMID- 24919801
TI  - The interaction of mastery motivation, motor abilities, the appropriate task, and
      the therapeutic environment.

PMID- 24919802
TI  - Sleep timing and longitudinal weight gain in 4- and 5-year-old children.
AB  - BACKGROUND AND OBJECTIVE: Short night-time sleep duration is a possible factor
      contributing to childhood obesity. Our objective was to evaluate associations
      between sleep timing (including bedtime and waketime) and weight gain in 4- to 5
      year-old children. METHODS: We used cross-sectional and longitudinal regression
      analyses of a large, nationally representative sample of children from the Early
      Childhood Longitudinal Study-Birth Cohort. Data regarding the timing and duration
      of weekday sleep were assessed via parent questionnaire. Short sleep duration,
      late bedtime and early waketime were defined as those greater than one standard
      deviation from the mean for the group. RESULTS: Using linear regression adjusted
      for confounders, sleep duration at 4 and 5 years and bedtime at 5 years were
      linked to body mass index (BMI) z-score (P < 0.001). Odds of obesity were higher
      at 4 years for children sleeping <9.44 h nightly (adjusted odds ratio 1.35,
      confidence interval 1.02-1.78, P < 0.05) and at 5 years for children going to bed
      at 9:00 pm or later (1.49, 1.16-1.45, P < 0.01) or waking before 6:30 am (1.23,
      1.01-15.51, P < 0.05). Assessed longitudinally, both short sleep duration (P <
      0.05) and later bedtime at 4 years (P < 0.01) were associated with increases in
      BMI z-score between 4 and 5 years. CONCLUSIONS: Children with shorter night-time
      sleep durations and later bedtimes were more likely to be obese and to gain
      weight over time. Pediatricians should encourage families to place children to
      bed at earlier times to promote longer sleep duration as a potential means of
      controlling weight gain.

PMID- 24919803
TI  - Human impact on fish sensory systems in the long term: an evolutionary
      perspective.
AB  - Humans have severely impacted global ecosystems and this shows few signs of
      abating. Many aspects of an animal's biology, including its sensory systems, may
      be adversely influenced by pollutants and environmental noise. This review
      focuses on whether and/or how various environmental disturbances disrupt the
      sensory systems of fishes. As critical as it is to document and understand the
      current effects of the human footprint, it is also important to consider how
      organisms might adapt to these impacts over the long term. The present paper
      outlines the sources of genetic and genomic variation upon which natural
      selection can act and then reviews examples of known genetic contributions of
      variation in fish chemosensory, visual and acoustico-lateralis systems. 

PMID- 24919804
TI  - B-lymphoid tyrosine kinase (Blk) is an oncogene and a potential target for
      therapy with dasatinib in cutaneous T-cell lymphoma (CTCL).

PMID- 24919805
TI  - Revisiting guidelines for integration of flow cytometry results in the WHO
      classification of myelodysplastic syndromes-proposal from the
      International/European LeukemiaNet Working Group for Flow Cytometry in MDS.
AB  - Definite progress has been made in the exploration of myelodysplastic syndromes
      (MDS) by flow cytometry (FCM) since the publication of the World Health
      Organization 2008 classification of myeloid neoplasms. An international working
      party initiated within the European LeukemiaNet and extended to include members
      from Australia, Canada, Japan, Taiwan and the United States has, through several
      workshops, developed and subsequently published consensus recommendations. The
      latter deal with preanalytical precautions, and propose small and large panels,
      which allow evaluating immunophenotypic anomalies and calculating myelodysplasia
      scores. The current paper provides guidelines that strongly recommend the
      integration of FCM data with other diagnostic tools in the diagnostic work-up of
      MDS. 

PMID- 24919806
TI  - Bioinformatic analyses of CALR mutations in myeloproliferative neoplasms support
      a role in signaling.

PMID- 24919808
TI  - Predicting multiple myeloma disease activity by analyzing natural calcium
      isotopic composition.

PMID- 24919809
TI  - Interfaces of ionic liquids. Preface.

PMID- 24919807
TI  - Cell-based strategies to manage leukemia relapse: efficacy and feasibility of
      immunotherapy approaches.
AB  - When treatment fails, the clinical outcome of acute leukemia patients is usually
      very poor, particularly when failure occurs after transplantation. A second
      allogeneic stem cell transplant could be envisaged as an effective and feasible
      salvage option in younger patients having a late relapse and an available donor.
      Unmanipulated or minimally manipulated donor T cells may also be effective in a
      minority of patients but the main limit remains the induction of severe graft
      versus-host disease. This clinical complication has brought about a huge research
      effort that led to the development of leukemia-specific T-cell therapy aiming at
      the direct recognition of leukemia-specific rather than minor histocompatibility
      antigens. Despite a great scientific interest, the clinical feasibility of such
      an approach has proven to be quite problematic. To overcome this limitation, more
      research has moved toward the choice of targeting commonly expressed
      hematopoietic specific antigens by the genetic modification of unselected T
      cells. The best example of this is represented by the anti-CD19 chimeric antigen
      receptor (CD19.CAR) T cells. As a possible alternative to the genetic
      manipulation of unselected T cells, specific T-cell subpopulations with in vivo
      favorable homing and long-term survival properties have been genetically modified
      by CAR molecules. Finally, the use of naturally cytotoxic effector cells such as
      natural killer and cytokine-induced killer cells has been proposed in several
      clinical trials. The clinical development of these latter cells could also be
      further expanded by additional genetic modifications using the CAR technology. 

PMID- 24919810
TI  - Aberrant mucosal lymphocyte number and subsets in the colon of post-infectious
      irritable bowel syndrome patients.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is characterized by chronic abdominal
      symptoms such as pain, discomfort, and altered bowel habits. A subset of IBS
      patients, denoted as post-infectious IBS (PI-IBS) patients, develop symptoms
      after an enteric infection. Distinct abnormalities in the gut mucosa, including
      mucosal inflammation, have been proposed to contribute to or be the cause of PI
      IBS. This study investigated lymphocyte subsets in PI-IBS patients compared to
      healthy controls. MATERIALS AND METHODS: Ten PI-IBS patients and nine healthy
      controls participated. All PI-IBS patients met the Rome III diagnostic criteria
      for IBS and reported sustained symptoms at least 1 year after an episode of acute
      gastroenteritis. Intraepithelial lymphocytes and lamina propria lymphocytes
      (LPLs), isolated from mucosal tissue samples, were stained and analyzed for a
      comprehensive set of cell markers using flow cytometry. RESULTS: The number of
      LPLs in PI-IBS was significantly increased compared to those in healthy controls
      (p < 0.05). PI-IBS patients showed significantly increased proportions of
      CD45RO(+) CD4(+) activated/memory T cells (p < 0.05) and double-positive CD4(+)
      CD8(+) cells (p < 0.05), respectively, in the lamina propria. The number of
      CD19(+) LPLs was decreased in PI-IBS patients compared to healthy controls (p <
      0.001). CONCLUSION: This study presents new evidence that PI-IBS is associated
      with a sustained aberrant mucosal immune response and support future studies of
      anti-inflammatory or immune-modulating treatments in these patients.

PMID- 24919812
TI  - Adsorbate-induced structural changes in 1-3 nm platinum nanoparticles.
AB  - We investigated changes in the Pt-Pt bond distance, particle size, crystallinity,
      and coordination of Pt nanoparticles as a function of particle size (1-3 nm) and
      adsorbate (H2, CO) using synchrotron radiation pair distribution function (PDF)
      and X-ray absorption spectroscopy (XAS) measurements. The ~1 nm Pt nanoparticles
      showed a Pt-Pt bond distance contraction of ~1.4%. The adsorption of H2 and CO at
      room temperature relaxed the Pt-Pt bond distance contraction to a value close to
      that of bulk fcc Pt. The adsorption of H2 improved the crystallinity of the small
      Pt nanoparticles. However, CO adsorption generated a more disordered fcc
      structure for the 1-3 nm Pt nanoparticles compared to the H2 adsorption Pt
      nanoparticles. In situ XANES measurements revealed that this disorder results
      from the electron back-donation of the Pt nanoparticles to CO, leading to a
      higher degree of rehybridization of the metal orbitals in the Pt-adsorbate
      system. 

PMID- 24919811
TI  - MicroRNA-206 overexpression promotes apoptosis, induces cell cycle arrest and
      inhibits the migration of human hepatocellular carcinoma HepG2 cells.
AB  - MicroRNA-206 (miR-206) is known to regulate cell proliferation and migration and
      is involved in various types of cancer. However, the role of miR-206 in human
      hepatocellular carcinoma (HHC) has not been previously reported. In the present
      study, the expression of Notch3 in HCC and adjacent non-neoplastic tissue was
      immunohistochemically assessed on formalin-fixed, paraffin-embedded sections. miR
      206 mimics were transiently transfected into HepG2 cells using LipofectamineTM
      2000. Subsequently, we evaluated the role of miR-206 in cell proliferation,
      apoptosis, cell cycle arrest and migration by MTS assay, Hoechst 33342 staining,
      Annexin V-FITC/PI assay, flow cytometry and wound healing assay. Using
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) and
      western blot analysis, we detected the expression of Notch3, Bax, Bcl-2, Hes1,
      p57 and matrix metalloproteinase (MMP)-9 at the mRNA and protein level,
      respectively. In addition, we measured the expression of miR-206 at the mRNA
      level and that of caspase-3 at the protein level. After miR-206 was upregulated
      in HepG2 cells, Notch3, Hes1, Bcl-2 and MMP-9 were downregulated both at the mRNA
      and protein level, whereas p57 and Bax were upregulated. Cleaved caspase-3
      protein expression was also markedly increased. Cell proliferation was
      significantly attenuated and apoptosis was markedly increased. Furthermore, miR
      206 overexpression induced cell cycle arrest and inhibited the migration of HepG2
      cells. Taken together, our results uggest that miR-206 is a potential regulator
      of apoptosis, the cell cycle and migration in HepG2 cells and that it has the
      potential for use in the targeted therapy of HCC and is a novel tumor suppressor.

PMID- 24919813
TI  - Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in
      Parkinson's disease.
AB  - Dopamine agonists (DA) are often used as first-line monotherapy for the
      symptomatic control of Parkinson's disease (PD). However, DA monotherapy
      typically becomes inadequate within a few years, at which time the DA dosage must
      be increased or other antiparkinsonian medications added. Adding a monoamine
      oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control
      while maintaining good safety and tolerability. We conducted an 18-week,
      randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add
      on to DA therapy (ropinirole >= 6 mg/d or pramipexole >= 1.0 mg/d) in early PD
      patients whose conditions were not adequately controlled on their current
      treatment regimen. The primary efficacy variable was the change in total Unified
      Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from
      baseline to week 18, comparing rasagiline and placebo groups. The modified intent
      to-treat (ITT) population included 321 subjects whose mean +/- SD age was 62.6 +/
      9.7, and duration of PD was 2.1 +/- 2.1 years. Results demonstrated a
      significantly greater improvement in total UPDRS scores from baseline to week 18
      in the rasagiline group compared with the placebo group (least squares [LS] mean
      difference +/- SE, -2.4 +/- 0.95; 95% confidence interval [CI], -4.3, -0.5; P =
      0.012). Mean improvement (LS mean +/- SE) was -3.6 +/- 0.68 in the rasagiline
      group and -1.2 +/- 0.68 in the placebo group. Rasagiline was well tolerated, and
      the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4%
      vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1
      mg/d provided statistically significant improvement when added to dopamine
      agonist therapy and was well tolerated.

PMID- 24919814
TI  - Two novel alleles HLA-A*02:433 and HLA-A*02:434 identified in Saudi bone marrow
      donors using sequence-based typing.
AB  - In this report, we present two novel HLA-A alleles: HLA-A*02:433 and HLA
      A*02:434. These alleles were identified by sequence-based typing method (SBT), in
      two donors for the Saudi Bone Marrow Donor Registry (SBMDR). Allele A*02:433 is
      identical to A*02:05:01G except for a G to A substitution at nucleotide position
      449 in exon 2. This substitution results in glycine to serine substitution at
      position 83. Whereas, allele A*02:434 is identical to A*02:01:01G except for a C
      to A substitution at nucleotide position 245 in exon 2, which results in
      phenylalanine to threonine substitution at position 15. The generation of both
      alleles appears to be the result of nucleotide point mutation involving 02:01:01
      and 02:05:01. 

PMID- 24919815
TI  - A reconstructed metastasis model to recapitulate the metastatic spread in vitro.
AB  - Metastasis remains a leading cause of morbidity and mortality from solid tumors.
      Lack of comprehensive systems to study the progression of metastasis contributes
      to the low success of treatment. We developed a novel three-dimensional in vitro
      reconstructed metastasis (rMet) model that incorporates extracellular matrix
      (ECM) elements characteristic of the primary (breast, prostate, or lung) and
      metastatic (bone marrow, BM) sites. A cytokine-rich liquid interphase separates
      the primary and distant sites, further recapitulating circulation. Similar to
      main events underlying the metastatic cascade, the rMet model fractionated human
      tumor cell lines into sub-populations with distinct invasive and migratory
      abilities: (i) a primary tumor-like fraction mainly consisting of non-migratory
      spheroids; (ii) an invasive fraction that invaded through the primary tumor ECM,
      but failed to acquire anchorage-independence and reach the BM; and (iii) a highly
      migratory BM-colonizing population that invaded the primary ECM, survived in the
      "circulation-like" media, and successfully invaded and proliferated within BM
      ECM. BM-colonizing fractions successfully established metastatic bone lesions in
      vivo, whereas the tumor-like spheroids failed to engraft the bones, showing the
      ability of the rMet model to faithfully select for highly aggressive sub
      populations with a propensity to colonize a metastatic site. By applying the rMet
      model to study real-time ECM remodeling, we show that tumor cells secrete
      collagenolytic enzymes for invading the primary site ECM but not for entering the
      BM ECM, indicating possible differences in ECM remodeling mechanisms at primary
      tumor versus metastatic sites. 

PMID- 24919816
TI  - iPLA2beta knockout mouse, a genetic model for progressive human motor disorders,
      develops age-related neuropathology.
AB  - Calcium-independent phospholipase A2 group VIa (iPLA2beta) preferentially
      releases docosahexaenoic acid (DHA) from the sn-2 position of phospholipids.
      Mutations of its gene, PLA2G6, are found in patients with several progressive
      motor disorders, including Parkinson disease. At 4 months, PLA2G6 knockout mice
      (iPLA2beta(-/-)) show minimal neuropathology but altered brain DHA metabolism. By
      1 year, they develop motor disturbances, cerebellar neuronal loss, and striatal
      alpha-synuclein accumulation. We hypothesized that older iPLA2beta(-/-) mice also
      would exhibit inflammatory and other neuropathological changes. Real-time
      polymerase chain reaction and Western blotting were performed on whole brain
      homogenate from 15 to 20-month old male iPLA2beta(-/-) or wild-type (WT) mice.
      These older iPLA2beta(-/-) mice compared with WT showed molecular evidence of
      microglial (CD-11b, iNOS) and astrocytic (glial fibrillary acidic protein)
      activation, disturbed expression of enzymes involved in arachidonic acid
      metabolism, loss of neuroprotective brain derived neurotrophic factor, and
      accumulation of cytokine TNF-alpha messenger ribonucleic acid, consistent with
      neuroinflammatory pathology. There was no evidence of synaptic loss, of reduced
      expression of dopamine active reuptake transporter, or of accumulation of the
      Parkinson disease markers Parkin or Pink1. iPLA2gamma expression was unchanged.
      iPLA2beta deficient mice show evidence of neuroinflammation and associated
      neuropathology with motor dysfunction in later life. These pathological
      biomarkers could be used to assess efficacy of dietary intervention, antioxidants
      or other therapies on disease progression in this mouse model of progressive
      human motor diseases associated with a PLA2G6 mutation. 

PMID- 24919818
TI  - High frequency of TTTY2-like gene-related deletions in patients with idiopathic
      oligozoospermia and azoospermia.
AB  - Genes located on Y chromosome and expressed in testis are likely to be involved
      in spermatogenesis. TTTY2 is a Y-linked multicopy gene family of unknown function
      that includes TTTY2L2A and TTTY2L12A at Yq11 and Yp11 loci respectively. Using
      PCR amplification, we screened for TTTY2L2A- and TTTY2L12A-associated deletions,
      in 94 Greek men with fertility problems. Patients were divided into three groups
      as following: group A (n = 28) included men with idiopathic moderate
      oligozoospermia, group B (n = 34) with idiopathic severe oligozoospermia and
      azoospermia, and group C (n = 32) with oligo- and azoospermia of various known
      etiologies. No deletions were detected in group C patients and 50 fertile
      controls. However, two patients from group A had deletions in TTTY2L2A (7.1%) and
      six in TTTY2L12A (21.4%), whereas from group B, four patients had deletions in
      TTTY2L2A (11.8%) and 10 in TTTY2L12A (29.4%). In addition, five patients from
      both groups A and B (8%) appeared to have deletions in both studied TTTY2 genes,
      although these are located very far apart. These results indicate that the TTTY2
      gene family may play a significant role in spermatogenesis and suggest a possible
      mechanism of nonhomologous recombinational events that may cause genomic
      instability and ultimately lead to male infertility. 

PMID- 24919817
TI  - Pretreatment by evodiamine is neuroprotective in cerebral ischemia: up-regulated
      pAkt, pGSK3beta, down-regulated NF-kappaB expression, and ameliorated BBB
      permeability.
AB  - Inflammatory damage plays an important role in cerebral ischemic pathogenesis and
      may represent a target for treatment. Evodiamine (Evo) has been proved to elicit
      a variety of biological effects through its anti-inflammatory property in the
      treatment of infectious disease, Alzheimer's disease and hypoxia-induced
      inflammatory response. Whether this protective effect applies to cerebral
      ischemic injury, we therefore investigated the potential neuroprotective role of
      Evo and the underlying mechanisms. Male Institute of Cancer Research (ICR) mice
      were subjected to permanent middle cerebral artery occlusion (pMCAO) and randomly
      divided into five groups: Sham (sham-operated + 1% DMSO + 0.5% tween80), pMCAO
      (pMCAO + 0.9% saline), Vehicle (pMCAO + 1% DMSO + 0.5% tween80), Evo-L (Vehicle +
      Evo 50 mg/kg) and Evo-H (Vehicle + Evo 100 mg/kg) groups. Evo was administered
      intragastrically twice daily for 3 days, and once again 30 min before mouse brain
      ischemia was induced by pMCAO. Neurological deficit, brain water content and
      infarct size were measured at 24 h after stroke. The expression of pAkt,
      pGSK3beta, NF-kappaB and claudin-5 in ischemic cerebral cortex was analyzed by
      western blot and qRT-PCR. Compared with Vehicle group, Evo significantly
      ameliorated neurological deficit, brain water content and infarct size,
      upregulated the expression of pAkt, pGSK3beta and claudin-5, and downregulated
      the nuclear accumulation of NF-kappaB (P < 0.05). Evo protected the brain from
      ischemic damage caused by pMCAO; this effect may be through upregulation of pAkt,
      pGSK3beta and claudin-5, and downregulation of NF-kappaB expression.

PMID- 24919819
TI  - Case report of a robotic-assisted laparoscopic repair of a giant incarcerated
      recurrent inguinal hernia containing bladder and ureters.
AB  - BACKGROUND: Robotic surgery is particularly useful in pelvic procedures, such as
      prostatectomy and low anterior resection. The paper describes a robotic-assisted
      repair of a giant bladder- and ureter-containing incarcerated inguinal hernia.
      METHODS AND RESULTS: A 53-year-old man had previously undergone repair of a left
      inguinal hernia. He presented to our clinic complaining of difficulty urinating
      and a large bulge in his left scrotum. CT revealed a giant left scrotal hernia
      containing the bladder and both ureters. The patient underwent robotic-assisted
      laparoscopic repair. The bladder and both ureters were carefully dissected free
      from the scrotum, while preserving the testicle and spermatic cord. A 6*4 inch
      pre-peritoneal polyester composite mesh was then used to repair the defect.
      CONCLUSION: Incarcerated, recurrent inguinal hernias are challenging repairs.
      Robotic-assisted repair allows for fine dissection, and is an excellent
      alternative to open surgery for a difficult inguinal hernia.

PMID- 24919820
TI  - Ipragliflozin in combination with metformin for the treatment of Japanese
      patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo
      controlled study.
AB  - This multicenter, double-blind, placebo-controlled study examined the efficacy
      and safety of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in
      combination with metformin in Japanese patients with type 2 diabetes mellitus
      (T2DM). Patients were randomized in a 2 : 1 ratio to 50 mg ipragliflozin (n =
      112) or placebo (n = 56) once daily for 24 weeks, followed by a 28-week open
      label extension in which all patients received 50 or 100 mg ipragliflozin, while
      continuing metformin. The primary outcome was the change in glycated haemoglobin
      (HbA1c) from baseline to week 24. HbA1c decreased significantly in the
      ipragliflozin group (-0.87%; adjusted mean difference from placebo: -1.30%; p <
      0.001). The overall incidence of treatment-emergent adverse events was similar in
      both groups, although pollakiuria and constipation were more common in the
      ipragliflozin group; thus, ipragliflozin significantly improved glycaemic control
      and reduced body weight without major safety issues in Japanese patients with
      T2DM.

PMID- 24919821
TI  - A stability indicating HPLC method for the determination of clobazam and its
      basic degradation product characterization.
AB  - BACKGROUND: Clobazam is used for the treatment of different types of seizure and
      epilepsy. The present research is undertaken to study the systematic forced
      degradation of clobazam and to identify its main degradation product under basic
      conditions. METHODS: The degradation of clobazam was studied under different
      conditions. Clobazam and its degradation products were separated using a Nova-Pak
      C18 column and a mixture of KH2PO4 50 mM (pH 8.5) and acetonitrile (50:50, v/v)
      as the mobile phase with UV detection at 230 nm. RESULTS: The within-day and
      between-day precision values in the calibration range of 0.1-20 MUg/ml were
      within 0.5-1.5%. Clobazam was relatively stable in solid from under exposure to
      visible and UV light and also heat. The clobazam aqueous solution of clobazam was
      more labile under exposure to visible and UV light. The bulk drug was
      significantly degraded under exposure to 2 M HCl, 0.1 M NaOH or 3% H2O2. Using
      the tablet powder, higher degradation rates were observed under different stress
      conditions. The main degradation product of clobazam under basic condition was
      subsequently characterized. CONCLUSION: The developed method could be used for
      the determination of clobazam in the presence of its degradation products with
      acceptable precision and accuracy. The applicability of the proposed method was
      evaluated in commercial dosage forms analysis.

PMID- 24919822
TI  - The use of antidepressant medication in Parkinson's disease patients is not
      affected by the type of antiparkinson medication.
AB  - Previous studies have suggested that dopamine agonists have an antidepressant
      effect in Parkinson's disease (PD) patients. We examined whether fewer PD
      patients used antidepressant medication, when they were first treated with a
      dopamine agonist compared to other PD medications. PD patients diagnosed in
      Denmark were identified, and the diagnosis was confirmed by a review of the
      medical record. Antidepressant medication was assessed using the Danish National
      Prescription Registry. We used Cox proportional hazards regression to model the
      association between PD medications and time to antidepressant prescription. The
      type of PD medication first prescribed did not affect the subsequent use of
      antidepressants. 

PMID- 24919823
TI  - Sialorrhea in patients with Parkinson's disease: safety and administration of
      botulinum neurotoxin.
AB  - Sialorrhea may present as a troublesome symptom in patients suffering from
      Parkinson's disease. Current options for treatment include anticholinergic drugs,
      irradiation, surgery, oral-motor and behavioural therapies, and injection of
      botulinum neurotoxin (BoNT) in the salivary glands. The aim of this study is to
      evaluate the safety and administration of BoNT as a treatment for sialorrhea in
      patients with Parkinson's disease (PD) based on a review of the studies conducted
      so far in this field. A PubMed search was conducted using the major keywords
      sialorrhea, botulinum neurotoxin, botulinum toxin and Parkinson's disease. The
      literature search identified 12 articles, which were selected for further
      analysis. Few adverse effects were described in the studies included in this
      present review. Various treatment strategies, including different medication
      dosages, were applied in the studies. BoNT treatment is safe for sialorrhea in
      patients with PD. Positive effect is well documented, and there have been
      relatively few reported adverse effects, which have been mild and transient.
      Based on this review, a treatment algorithm is proposed. Ultrasound guidance may
      not be necessary when injecting the parotid gland but may improve the effect and
      safety of administration, especially when injecting the submandibular glands.

PMID- 24919824
TI  - Quality of life and mild cognitive impairment in early Parkinson's disease: does
      subtype matter?
AB  - We evaluated the association between mild cognitive impairment (MCI) subtypes and
      quality of life (QoL) in 219 newly diagnosed Parkinson's disease (PD) patients
      without dementia. Participants completed neuropsychological tests of attention,
      executive function, visuospatial function, memory, and language, and reported QoL
      using the Parkinson's Disease Questionnaire. Impairments were most common in
      executive function, memory and attention. MCI subtypes were classified according
      to Movement Disorder Society Task Force criteria. More severe cognitive
      impairment was associated with poorer quality of life (p = 0.01), but subtype of
      impairment was not (p > 0.10), suggesting that the nature of cognitive impairment
      is less significant than its severity. 

PMID- 24919825
TI  - Pocket echocardiography system for detection of patent ductus arteriosus in
      neonates.
AB  - BACKGROUND: Neonates are commonly referred for a cardiology consult and an
      echocardiogram to rule out patent ductus arteriosus (PDA). OBJECTIVES: Evaluate
      the usefulness of current pocket echocardiography system (PES) in PDA detection
      compared to traditional full-featured echo system (FFES). HYPOTHESIS: The
      determination of the presence of a PDA in neonates can be done using PES.
      METHODS: Fifty newborns with orders for echo evaluation were included in this
      study. A 5-minute PES scan was performed first. Then a full echo study was
      performed on a traditional FFES. Images were evaluated by three pediatric
      cardiologists blinded to the patients and the FFES results. RESULTS: The overall
      accuracy of reviewers rating PES versus FFES to rule in PDA had low false
      positive rates 9.5% (95% CI: 1.2-30%), 11.8% (95% CI: 1.5-36%), 11.1% (95% CI:
      1.4-35%) and the false-negative rate to rule out PDA was 0% (95% CI: 0-18%), 5.5%
      (95% CI: 0.14-27%), 0% (95% CI: 0-26%) for each reviewer 1, 2, and 3,
      respectively. Upon further analysis, PES scan was shown not to be accurate on
      infants with body weight below 1000 g with encouraging results for infants above
      1000 g and those >37 weeks gestational age. CONCLUSIONS: Our results suggest that
      the current PES could potentially be used in larger and near-term infants but has
      less than acceptable performance in low birth weight and premature infants in
      determining who should undergo a FFES study for persistent PDA diagnosis.
      Improvements in the technology along with developing limited training protocols
      for noncardiology personnel should make it possible for PES scan to be used as a
      screening tool and as an extension of physical examination especially in limited
      resource settings.

PMID- 24919826
TI  - The emerging science of quantitative imaging biomarkers terminology and
      definitions for scientific studies and regulatory submissions.
AB  - The development and implementation of quantitative imaging biomarkers has been
      hampered by the inconsistent and often incorrect use of terminology related to
      these markers. Sponsored by the Radiological Society of North America, an
      interdisciplinary group of radiologists, statisticians, physicists, and other
      researchers worked to develop a comprehensive terminology to serve as a
      foundation for quantitative imaging biomarker claims. Where possible, this
      working group adapted existing definitions derived from national or international
      standards bodies rather than invent new definitions for these terms. This
      terminology also serves as a foundation for the design of studies that evaluate
      the technical performance of quantitative imaging biomarkers and for studies of
      algorithms that generate the quantitative imaging biomarkers from clinical scans.
      This paper provides examples of research studies and quantitative imaging
      biomarker claims that use terminology consistent with these definitions as well
      as examples of the rampant confusion in this emerging field. We provide
      recommendations for appropriate use of quantitative imaging biomarker
      terminological concepts. It is hoped that this document will assist researchers
      and regulatory reviewers who examine quantitative imaging biomarkers and will
      also inform regulatory guidance. More consistent and correct use of terminology
      could advance regulatory science, improve clinical research, and provide better
      care for patients who undergo imaging studies. 

PMID- 24919827
TI  - Closed-form fiducial confidence intervals for some functions of independent
      binomial parameters with comparisons.
AB  - Approximate closed-form confidence intervals (CIs) for estimating the difference,
      relative risk, odds ratio, and linear combination of proportions are proposed.
      These CIs are developed using the fiducial approach and the modified normal-based
      approximation to the percentiles of a linear combination of independent random
      variables. These confidence intervals are easy to calculate as the computation
      requires only the percentiles of beta distributions. The proposed confidence
      intervals are compared with the popular score confidence intervals with respect
      to coverage probabilities and expected widths. Comparison studies indicate that
      the proposed confidence intervals are comparable with the corresponding score
      confidence intervals, and better in some cases, for all the problems considered.
      The methods are illustrated using several examples.

PMID- 24919828
TI  - Statistical issues in the comparison of quantitative imaging biomarker algorithms
      using pulmonary nodule volume as an example.
AB  - Quantitative imaging biomarkers are being used increasingly in medicine to
      diagnose and monitor patients' disease. The computer algorithms that measure
      quantitative imaging biomarkers have different technical performance
      characteristics. In this paper we illustrate the appropriate statistical methods
      for assessing and comparing the bias, precision, and agreement of computer
      algorithms. We use data from three studies of pulmonary nodules. The first study
      is a small phantom study used to illustrate metrics for assessing repeatability.
      The second study is a large phantom study allowing assessment of four algorithms'
      bias and reproducibility for measuring tumor volume and the change in tumor
      volume. The third study is a small clinical study of patients whose tumors were
      measured on two occasions. This study allows a direct assessment of six
      algorithms' performance for measuring tumor change. With these three examples we
      compare and contrast study designs and performance metrics, and we illustrate the
      advantages and limitations of various common statistical methods for quantitative
      imaging biomarker studies. 

PMID- 24919830
TI  - A multiphase non-linear mixed effects model: An application to spirometry after
      lung transplantation.
AB  - In medical sciences, we often encounter longitudinal temporal relationships that
      are non-linear in nature. The influence of risk factors may also change across
      longitudinal follow-up. A system of multiphase non-linear mixed effects model is
      presented to model temporal patterns of longitudinal continuous measurements,
      with temporal decomposition to identify the phases and risk factors within each
      phase. Application of this model is illustrated using spirometry data after lung
      transplantation using readily available statistical software. This application
      illustrates the usefulness of our flexible model when dealing with complex non
      linear patterns and time-varying coefficients.

PMID- 24919829
TI  - Quantitative imaging biomarkers: a review of statistical methods for computer
      algorithm comparisons.
AB  - Quantitative biomarkers from medical images are becoming important tools for
      clinical diagnosis, staging, monitoring, treatment planning, and development of
      new therapies. While there is a rich history of the development of quantitative
      imaging biomarker (QIB) techniques, little attention has been paid to the
      validation and comparison of the computer algorithms that implement the QIB
      measurements. In this paper we provide a framework for QIB algorithm comparisons.
      We first review and compare various study designs, including designs with the
      true value (e.g. phantoms, digital reference images, and zero-change studies),
      designs with a reference standard (e.g. studies testing equivalence with a
      reference standard), and designs without a reference standard (e.g. agreement
      studies and studies of algorithm precision). The statistical methods for
      comparing QIB algorithms are then presented for various study types using both
      aggregate and disaggregate approaches. We propose a series of steps for
      establishing the performance of a QIB algorithm, identify limitations in the
      current statistical literature, and suggest future directions for research. 

PMID- 24919831
TI  - Quantitative imaging biomarkers: a review of statistical methods for technical
      performance assessment.
AB  - Technological developments and greater rigor in the quantitative measurement of
      biological features in medical images have given rise to an increased interest in
      using quantitative imaging biomarkers to measure changes in these features.
      Critical to the performance of a quantitative imaging biomarker in preclinical or
      clinical settings are three primary metrology areas of interest: measurement
      linearity and bias, repeatability, and the ability to consistently reproduce
      equivalent results when conditions change, as would be expected in any clinical
      trial. Unfortunately, performance studies to date differ greatly in designs,
      analysis method, and metrics used to assess a quantitative imaging biomarker for
      clinical use. It is therefore difficult or not possible to integrate results from
      different studies or to use reported results to design studies. The Radiological
      Society of North America and the Quantitative Imaging Biomarker Alliance with
      technical, radiological, and statistical experts developed a set of technical
      performance analysis methods, metrics, and study designs that provide
      terminology, metrics, and methods consistent with widely accepted metrological
      standards. This document provides a consistent framework for the conduct and
      evaluation of quantitative imaging biomarker performance studies so that results
      from multiple studies can be compared, contrasted, or combined. 

PMID- 24919832
TI  - The potential for increased power from combining P-values testing the same
      hypothesis.
AB  - The conventional approach to hypothesis testing for formal inference is to
      prespecify a single test statistic thought to be optimal. However, we usually
      have more than one test statistic in mind for testing the null hypothesis of no
      treatment effect but we do not know which one is the most powerful. Rather than
      relying on a single p-value, combining p-values from prespecified multiple test
      statistics can be used for inference. Combining functions include Fisher's
      combination test and the minimum p-value. Using randomization-based tests, the
      increase in power can be remarkable when compared with a single test and Simes's
      method. The versatility of the method is that it also applies when the number of
      covariates exceeds the number of observations. The increase in power is large
      enough to prefer combined p-values over a single p-value. The limitation is that
      the method does not provide an unbiased estimator of the treatment effect and
      does not apply to situations when the model includes treatment by covariate
      interaction.

PMID- 24919833
TI  - We need to talk about depot: effect of Community Treatment Order on depot
      antipsychotic medication compliance.
AB  - OBJECTIVE: The current study compares the compliance rates of patients on depot
      who were on Community Treatment Orders with those who were not on such Order with
      a view to objectively quantify the effect of Community Treatment Orders on depot
      antipsychotics medication compliance. METHODS: "Day difference" measurements
      between the scheduled depot data and the administered date were collected for
      both voluntary and involuntary patients receiving depot medication at the same
      community clinic over a 6-month period. RESULTS: The results demonstrated a trend
      for greater compliance to depot medications by those not on a Community Treatment
      Order compared with those who were, but there was no statistically significant
      difference between the two groups. CONCLUSIONS: The current study highlighted
      that while Community Treatment Order may be a reasonable short-term tool to
      encourage patients' compliance at an early treatment stage, ongoing effort should
      be put into improving patients' attitude towards depot medications to ensure a
      better long-term outcome for individuals with schizophrenia.

PMID- 24919834
TI  - Few older people in New Zealand who commit suicide receive specialist
      psychogeriatric services.
AB  - OBJECTIVE: Suicide in older people is a growing public health concern in many
      parts of the world. The literature on this issue is lacking in New Zealand. The
      aim of this study is to ascertain whether this group is accessing specialist
      psychogeriatric services. A retrospective case series study of completed suicides
      in older people (>=65 years) during a three-year period from January 2010 to
      December 2012 was performed. METHOD: An online survey detailing demographic and
      clinical information was completed by psychiatrists in 15 of the 20 District
      Health Boards in New Zealand. RESULTS: Only about 15% of older people who
      committed suicide were accessing specialist psychogeriatric services and the
      group with the highest suicide rate (men>=85 years) did not feature in specialist
      services. Depression (61%) was the most common diagnosis and nearly half (35%)
      had had contact with specialist services within three days prior to the suicide.
      Over half (52%) had a history of past suicide attempt(s). CONCLUSIONS: Older
      people who complete suicide are infrequently accessing specialist services. In
      those that do, there are questions to be answered regarding suicide prediction
      and prevention for this high-risk group of vulnerable individuals. More research
      is required targeting those not accessing specialist services, in particular the
      high risk group of older men. The role of general practitioner, community care,
      the assessment and management of depression and whether there is any access issue
      to specialist psychogeriatric services require elucidation.

PMID- 24919835
TI  - The erosion of psychiatrist-patient confidentiality by subpoenas.
AB  - OBJECTIVES: We explore the reasons for the prolific use of subpoenas to gain
      access to psychiatric records in Australia. We examine the applicable legal
      principles and practices at the New South Wales (NSW) and Commonwealth levels,
      aiming to develop recommendations for Australian Governments to curb the
      inappropriate and harmful use of subpoenas. CONCLUSION: Unfettered legal access
      to psychiatric records is inconsistent with professional ethical guidelines and
      risks undermining the provision of quality psychiatric care to the community. The
      existing legal provisions are failing to protect psychiatrist-patient
      confidentiality. In NSW, the onus is placed on the psychiatrist and/or patient to
      make a complicated application to the court, to direct that a subpoena be set
      aside on the grounds of "Professional Confidential Relationship Privilege." An
      absence of Commonwealth legislation to protect psychiatrist-patient
      confidentiality is used by some litigants in family law proceedings to
      disadvantage patients by stigmatising them, because they have consulted
      psychiatrists. We recommend that uniform legislation be implemented, giving
      effect to a primary rule of privilege with exceptions.

PMID- 24919836
TI  - Spatial elucidation of spinal cord lipid- and metabolite- regulations in
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease
      of the central nervous system that is characterized by motor neuron degeneration
      in the brain stem and the spinal cord. We employed time of flight secondary ion
      mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite-
      regulations in post mortem human spinal cord tissue from ALS patients to
      investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate
      analysis of image and spectral data were performed on thoracic human spinal cord
      sections. Multivariate statistics of the image data allowed delineation of
      anatomical regions of interest based on their chemical identity. Spectral data
      extracted from these regions were compared using two different approaches for
      multivariate statistics, for investigating ALS related lipid and metabolite
      changes. The results show a significant decrease for cholesterol, triglycerides,
      and vitamin E in the ventral horn of ALS samples, which is presumably a
      consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid
      lysophosphatidylcholine and its fragments were increased in ALS ventral spinal
      cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell
      death. ToF-SIMS imaging is a promising approach for chemical histology and
      pathology for investigating the subcellular mechanisms underlying motor neuron
      degeneration in amyotrophic lateral sclerosis. 

PMID- 24919837
TI  - Population pharmacokinetic and pharmacodynamic analysis of bosutinib.
AB  - Bosutinib is an orally active, competitive inhibitor of Src/Abl tyrosine kinases.
      A population pharmacokinetic model was developed using data pooled from 3 studies
      of patients (n = 870) with solid tumors or Philadelphia chromosome-positive
      leukemia. Patients (aged 18-91 y, weighing 35-221 kg) who received bosutinib 50
      to 600 mg orally with food each contributed 6-9 pharmacokinetic samples. The
      final pharmacokinetic model was a linear two-compartment model with first-order
      absorption, an absorption lag-time, and dose-dependent bioavailability. Oral
      absorption was relatively slow, with a half-time of 1.14 h and a lag-time of 0.87
      h; time to peak concentration was 5-6 h. Apparent clearance was 120 L/h. The
      apparent volume of the peripheral compartment was large with a slow turnover;
      alpha and beta half-lives were 19 h and 290 days, respectively. All parameters
      were estimated with acceptable precision (standard error <30%). No tested
      covariate (protocol, baseline demographic/clinical characteristics, or laboratory
      results) explained the high inter-individual variability of bosutinib
      pharmacokinetics. Therefore, adjusting bosutinib dose for body size (weight,
      surface area) would not provide benefit over fixed dosing. Using this exposure
      model in pharmacodynamic assessment of one study, adverse event incidence was
      shown to be similar in overall and bosutinib-responsive populations. 

PMID- 24919838
TI  - Interventional management of acute ischemic stroke: a systematic review.
AB  - OPINION STATEMENT: Historically, acute ischemic stroke (AIS) trials defined
      syndromes according to acute clinical presentation and post-ictus parenchymal
      imaging. With improvements in real-time arterial imaging, modern AIS treatment
      demands a structural approach based upon the level of cerebrovascular occlusion.
      The poor concordance of presenting National Institute of Health Stroke Scale
      (NIHSS) with vessel occlusion in recent trials bespeaks the need for an anatomic
      perspective. Specifically, patients with large-vessel occlusion (LVO) represent a
      distinct entity with a poorer prognosis than general AIS patients. Ongoing
      clinical trials and therapeutic strategies must recognize the varied natural
      history of AIS patients. Endovascular therapy offers promise in patients with the
      most severe strokes.

PMID- 24919839
TI  - In Memoriam: Olga Hudlicka (11.07.26-03.05.14).
AB  - Dr Olga Hudlicka, Professor Emeritus in the Department of Physiology, University
      of Birmingham Medical School, died suddenly on 3rd May not long after a fall. She
      was one of the best-known vascular physiologists of the last century,
      investigating control of blood flow and regulation of angiogenesis in skeletal
      and cardiac muscle. This article is protected by copyright. All rights reserved.

PMID- 24919840
TI  - Complete coverage of phantom limb and stump pain with constant current SCS
      system: a case report and review of the literature.
AB  - BACKGROUND: Spinal cord stimulator (SCS) technology has advanced over the past
      several years. However, our literature review revealed a lack of well-documented
      cases of successful treatment of phantom limb pain with percutaneous revision of
      previously placed systems. CASE REPORT: We present the case of a patient who
      suffered from debilitating bilateral lower extremity phantom limb pain despite
      having a SCS with a constant voltage system. We used fluoroscopy to successfully
      guide a percutaneous octapolar paddle lead to the right of the existing surgical
      paddle lead and a cylindrical quadrapolar lead in between. Finally, the older
      paddle lead was connected to an extension to make it compatible with the updated
      constant current system. The revised constant current SCS system provided
      bilateral coverage of the patient's pain, and at 1-year postoperative, the
      patient reported he had sustained coverage from his bilateral phantom limb pain.
      Our patient had complete coverage of his phantom limb pain after his previously
      placed SCS was changed from a constant voltage to a constant current system, and
      percutaneous leads were connected to his system. Adding percutaneous leads or
      switching generator types may benefit patients whose pain patterns have expanded
      since original SCS system placement. This case reports the complete coverage of
      phantom limb pain with a change from a constant voltage to a constant current SCS
      system and the addition of percutaneous leads to an existing SCS system.

PMID- 24919841
TI  - Effects of red pitaya juice supplementation on cardiovascular and hepatic changes
      in high-carbohydrate, high-fat diet-induced metabolic syndrome rats.
AB  - BACKGROUND: The fruit of Hylocereus polyrhizus, also known as red pitaya, and
      buah naga in Malay, is one of the tropical fruits of the cactus family,
      Cactaceae. Red pitaya has been shown to protect aorta from oxidative damage and
      improve lipid profiles in hypercholesterolemic rats probably due to
      phytochemicals content including phenolics and flavonoids. The aim of this study
      was to investigate the changes in cardiac stiffness, hepatic and renal function
      in high-carbohydrate, high-fat diet-induced obese rats following supplementation
      of red pitaya juice. METHODS: Total 48 male Wistar rats were divided into 4
      groups: corn-starch group (CS), corn-starch+red pitaya juice group (CRP), high
      carbohydrate, high fat group (HCHF) and high-carbohydrate, high fat+red pitaya
      juice (HRP). The intervention with 5% red pitaya juice was started for 8 weeks
      after 8 weeks initiation of the diet. Heart function was determined ex vivo with
      Langendorff hearts while plasma liver enzymes, uric acid and urea were measured
      using commercial kits. Total fat mass was determined with Dual-energy X-ray
      absorptiometry (DXA) scan. Glucose uptake was measured with Oral Glucose
      Tolerance Test (OGTT). Liver and cardiac structures were defined by histology.
      RESULTS: Supplementation of red pitaya juice for 8 weeks increased energy intake
      and abdominal circumference but no change in body fat and lean mass respectively.
      Also, there were a trend of uric acid and glucose normalization for HRP as
      compared to H-fed rats. Red pitaya juice treatment reduced ALP and ALT but caused
      significant increment in AST. Diastolic stiffness of the heart was reduced after
      supplementation of red pitaya juice in corn starch fed rats. However, the
      reduction was not significant in HRP rats in comparison with H rats. CONCLUSION:
      The present study concluded that red pitaya juice may serve as a complimentary
      therapy for attenuating some signs of metabolic syndrome.

PMID- 24919842
TI  - Reconceptualizing practice with multilingual children with speech sound
      disorders: people, practicalities and policy.
AB  - BACKGROUND: The speech and language therapy profession is required to provide
      services to increasingly multilingual caseloads. Much international research has
      focused on the challenges of speech and language therapists' (SLTs) practice with
      multilingual children. AIMS: To draw on the experience and knowledge of experts
      in the field to: (1) identify aspirations for practice, (2) propose
      recommendations for working effectively with multilingual children with speech
      sound disorders, and (3) reconceptualize understandings of and approaches to
      practice. METHODS & PROCEDURES: Fourteen members of the International Expert
      Panel on Multilingual Children's Speech met in Cork, Ireland, to discuss SLTs'
      practice with multilingual children with speech sound disorders. Panel members
      had worked in 18 countries and spoke nine languages. Transcripts of the 6-h
      discussion were analysed using Cultural-Historical Activity Theory (CHAT) as a
      heuristic framework to make visible the reality and complexities of SLTs'
      practice with multilingual children. OUTCOMES & RESULTS: Aspirations and
      recommendations for reconceptualizing approaches to practice with multilingual
      children with speech sound disorders included: (1) increased training for working
      with multilingual children, their families, and interpreters, (2) increased
      training for transcribing speech in many languages, (3) increased time and
      resources for SLTs working with multilingual children and (4) use of the
      International Classification of Functioning, Disability and Health (ICF-CY).
      CONCLUSIONS & IMPLICATIONS: The reality and complexities of practice identified
      in this paper highlight that it is not possible to formulate and implement one
      'gold standard' method of assessment and intervention for all multilingual
      children with speech sound disorders. It is possible, however, to underpin
      practice with a framework that ensures comprehensive assessment, accurate
      diagnosis and effective intervention. This paper proposes that by working towards
      the aspirations of the Expert Panel, SLTs can be empowered to facilitate
      appropriate services for multilingual children regardless of the context in which
      they live and the languages they speak.

PMID- 24919843
TI  - Construction and evaluation of a novel humanized HER2-specific chimeric receptor.
AB  - INTRODUCTION: The human epidermal growth factor receptor 2 (HER2) represents one
      of the most studied tumor-associated antigens (TAAs) for cancer immunotherapy.
      The monoclonal antibody (mAb) trastuzumab has improved the outcomes of patients
      with HER2+ breast cancer. However, a large number of HER2+ tumors are not
      responsive to, or become resistant to, trastuzumab-based therapy, and thus more
      effective therapies targeting HER2 are needed. METHODS: HER2-specific T cells
      were generated by the transfer of genes that encode chimeric antigen receptor
      (CAR). Using a multistep overlap extension PCR method, we constructed a novel,
      humanized HER2 CAR-containing, chA21 single-chain variable fragment (scFv) region
      of antigen-specific mAb and T-cell intracellular signaling chains made up of CD28
      and CD3zeta. An interferon gamma and interleukin 2 enzyme-linked immunosorbent
      assay and a chromium-51 release assay were used to evaluate the antitumor immune
      response of CAR T cells in coculture with tumor cells. Furthermore, SKBR3 tumor
      bearing nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were
      treated with HER2 CAR T cells to evaluate antitumor activity. Human CD3+ T cell
      accumulation in tumor xenograft was detected by immunohistochemistry. RESULTS:
      chA21-28z CAR was successfully constructed, and both CD4+ and CD8+ T cells were
      transduced. The expanded HER2 CAR T cells expressed a central memory phenotype
      and specifically reacted against HER2+ tumor cell lines. Furthermore, the SKBR3
      tumor xenograft model revealed that HER2 CAR T cells significantly inhibited
      tumor growth in vivo. Immunohistochemical analysis showed robust accumulation of
      human CD3+ T cells in regressing SKBR3 lesions. CONCLUSIONS: The results of this
      study show that novel chA21 scFv-based, HER2-specific CAR T cells not only
      recognized and killed HER2+ breast and ovarian cancer cells ex vivo but also
      induced regression of experimental breast cancer in vivo. Our data support
      further exploration of the HER2 CAR T-cell therapy for HER2-expressing cancers.

PMID- 24919845
TI  - First case of synophthalmia and albinism in the Pacific angel shark Squatina
      californica.
AB  - The first record in Mexican waters of albinism and synophthalmia (partial
      cyclopia) in the Pacific angel shark, Squatina californica is presented. Albinism
      is not lethal, but synophthalmia may cause the death of the individual
      immediately after birth. 

PMID- 24919844
TI  - Streptococcus agalactiae in Brazil: serotype distribution, virulence determinants
      and antimicrobial susceptibility.
AB  - BACKGROUND: Group B Streptococcus (GBS) remains a major cause of neonatal sepsis
      and is also associated with invasive and noninvasive infections in pregnant women
      and non-pregnant adults, elderly and patients with underlying medical conditions.
      Ten capsular serotypes have been recognized, and determination of their
      distribution within a specific population or geographical region is important as
      they are major targets for the development of vaccine strategies. We have
      evaluated the characteristics of GBS isolates recovered from individuals with
      infections or colonization by this microorganism, living in different geographic
      regions of Brazil. METHODS: A total of 434 isolates were identified and serotyped
      by conventional phenotypic tests. The determination of antimicrobial
      susceptibility was performed by the disk diffusion method. Genes associated with
      resistance to erythromycin (ermA, ermB, mefA) and tetracycline (tetK, tetL, tetM,
      tetO) as well as virulence-associated genes (bac, bca, lmb, scpB) were
      investigated using PCR. Pulsed-field gel electrophoresis (PFGE) was used to
      examine the genetic diversity of macrolide-resistant and of a number of selected
      macrolide-susceptible isolates. RESULTS: Overall, serotypes Ia (27.6%), II
      (19.1%), Ib (18.7%) and V (13.6%) were the most predominant, followed by
      serotypes IV (8.1%) and III (6.7%). All the isolates were susceptible to the beta
      lactam antimicrobials tested and 97% were resistant to tetracycline. Resistance
      to erythromycin and clindamycin were found in 4.1% and 3% of the isolates,
      respectively. Among the resistance genes investigated, tetM (99.3%) and tetO
      (1.8%) were detected among tetracycline-resistant isolates and ermA (39%) and
      ermB (27.6%) were found among macrolide-resistant isolates. The lmb and scpB
      virulence genes were detected in all isolates, while bac and bca were detected in
      57 (13.1%) and 237 (54.6%) isolates, respectively. Molecular typing by PFGE
      showed that resistance to erythromycin was associated with a variety of clones.
      CONCLUSION: These findings indicate that GBS isolates circulating in Brazil have
      a variety of phenotypic and genotypic characteristics, and suggest that macrolide
      resistant isolates may arise by both clonal spread and independent acquisition of
      resistance genes.

PMID- 24919846
TI  - Expression of latent membrane proteins in Epstein-Barr virus-transformed
      lymphocytes in vitro.
AB  - Infection with Epstein-Barr virus (EBV) induces activation and proliferation of B
      lymphocytes. Detection of latent membrane protein (LMP)-1 is used to identify the
      proliferative ability of B cells. However, changes in the expression levels of
      the three LMPs during EBV-induced B lymphocyte transformation, have not yet been
      reported. In the present study, the expression levels of LMP-1, LMP-2A and LMP-2B
      were compared between EBV-transformed B lymphocytes and paired normal
      lymphocytes. Seven lymphoblast cell lines were established by EBV infection of
      normal human lymphocytes in vitro. The expression levels of LMP genes and LMP-1
      protein were determined using quantitative (q)PCR and western blotting in
      lymphoblasts and normal lymphocytes, respectively. The expression of LMP1, LMP-2A
      and LMP-2B genes was significantly upregulated in EBV-induced lymphoblasts
      compared with the normal lymphocytes. The LMP-1 protein level was also
      significantly increased in EBV-transformed B lymphocytes. Expression of LMP1, LMP
      2A and LMP-2B genes was significantly upregulated in EBV-induced lymphoblasts,
      suggesting LMP genes are important in the transformation of human lymphocytes. 

PMID- 24919847
TI  - Director alignment relative to the temperature gradient in nematic liquid
      crystals studied by molecular dynamics simulation.
AB  - The director alignment relative to the temperature gradient in nematic liquid
      crystal model systems consisting of soft oblate or prolate ellipsoids of
      revolution has been studied by molecular dynamics simulation. The temperature
      gradient is maintained by thermostating different parts of the system at
      different temperatures by using a Gaussian thermostat. It is found that the
      director of the prolate ellipsoids aligns perpendicularly to the temperature
      gradient whereas the director of the oblate ellipsoids aligns parallel to this
      gradient. When the director is oriented in between the parallel and perpendicular
      orientations a torque is exerted forcing the director to the parallel or
      perpendicular orientation. Because of symmetry restrictions there is no linear
      dependence of the torque being a pseudovector on the temperature gradient being a
      polar vector in an axially symmetric system such as a nematic liquid crystal. The
      lowest possible order of this dependence is quadratic. Thus the torque is very
      weak when the temperature gradient is small, which may explain why this
      orientation phenomenon is hard to observe experimentally. In both cases the
      director attains the orientation that minimises the irreversible entropy
      production. 

PMID- 24919848
TI  - The role of hydroxo-bridged dinuclear species and the influence of "innocent"
      buffers in the reactivity of cis-[Co(III)(cyclen)(H2O)2]3+ and
      [Co(III)(tren)(H2O)2]3+ complexes with biologically relevant ligands at
      physiological pH.
AB  - In view of the relevance of the reactivity of inert tetraamine Co(III) complexes
      having two substitutionally active cis positions capable of interact with
      biologically relevant ligands, the study of the reaction of cis
      [Co(cyclen)(H2O)2](3+) and [Co(tren)(H2O)2](3+) with chlorides, inorganic
      phosphate and 5'-CMP (5'-cytidinemonophosphate) has been pursued at physiological
      pH. The results indicate that, in addition to the actuation of the expected
      labilising conjugate-base mechanism, the formation of mono and inert bis hydroxo
      bridged species is relevant for understanding their speciation and reactivity.
      The reactivity pattern observed also indicates the key role played by the
      "innocent" buffers frequently used in most in vitro studies, which can make the
      results unreliable in many cases. The differences between the reactivity of
      inorganic and biologically relevant phosphates has also been found to be
      remarkable, with outer-sphere hydrogen bonding interactions being a dominant
      factor for the process. While for the inorganic phosphate substitution process
      the formation of MU-eta(2)-OPO2O represents the termination of the reactivity
      monitored, for 5'-CMP only the formation of eta(1)-OPO3 species is observed,
      which evolve with time to the final dead-end bis hydroxo-bridged complexes. The
      promoted hydrolysis of the 5'-CMP phosphate has not been observed in any of the
      processes studied. 

PMID- 24919850
TI  - Qualifying stem cell sources: how to overcome potential pitfalls in regenerative
      medicine?
AB  - Regenerative medicine aims to replace lost cells and to restore damaged tissues
      and organs by either tissue-engineering approaches or stimulation of endogenous
      processes. Due to their biological properties, stem cells promise to be an
      effective source for such strategies. Especially adult multipotent stem cells
      (ASCs) are believed to be applicable in a broad range of therapies for the
      treatment of multifactorial diseases or age-related degeneration, although the
      molecular and cellular mechanisms underlying their regenerative function are
      often hardly described. Moreover, in some demanding clinical situations their
      efficiency remains limited. Thus, a basic understanding of ASCs regenerative
      function, their complex interplay with their microenvironment and how
      compromising conditions interfere with their efficiency is mandatory for any
      regenerative strategy. Concerning this matter, the impact of patient-specific
      constraints are often underestimated in research projects and their influence on
      the study results disregarded. Thus, researchers are urgently depending on well
      characterized tissue samples or cells that are connected with corresponding donor
      information, such as secondary diseases, medication. Here, we outline principle
      pitfalls during experimental studies using human samples, and describe a
      potential strategy to overcome these challenges by establishing a core unit for
      cell and tissue harvesting. This facility aims to bridge the gap between clinic
      and research laboratories by the provision of a direct link to the clinical
      operating theatres. Such a strategy clearly supports basic and clinical research
      in the conduct of their studies and supplies highly characterized human samples
      together with the corresponding donor information.

PMID- 24919851
TI  - Probiotics and broiler growth performance: a meta-analysis of randomised
      controlled trials.
AB  - 1. The aim of this meta-analysis was to investigate the effects of probiotics on
      the growth performance of broilers. PubMed, Scopus and Scholar Google databases
      were searched in all languages from 1980 to 2012. The studies in the meta
      analysis were only selected if they were randomised and controlled experiments
      using broilers without apparent disease and the results were published in peer
      reviewed journals. 2. A total of 48 and 46 studies were included to assess
      probiotic effects on body weight gain (BWG) and feed efficiency (FE),
      respectively. Probiotics increased BWG compared to controls (SMD = 0.661, 95% CI
      0.499 to 0.822) and improved FE (SMD = - 0.281, 95% CI -0.404 to -0.157) in the
      pooled standardised mean difference random effect model, considering the source
      of heterogeneity and publication biases. However, there are evidences of
      publication bias and heterogeneity, so the results of this meta-analysis should
      be considered with caution. Applying the Duval and Tweedie's trim-and-fill
      methods, the adjusted value for BWG was 0.0594 (95% CI -0.122 to 0.242), and the
      adjusted value for FE did not show any modifications. 3. The meta-analysis showed
      that application of probiotics via water resulted in greater BGW and FE than
      administration through the feed. The effect was not related to the use of mono
      strain or multi-strain probiotics, although it may depend on the strain used. The
      number of broilers and the duration of the experiments had an impact on the
      outcomes. 4. Additional studies should be conducted with the aim to identify the
      covariates which can explain the differences in the estimated effect sizes.

PMID- 24919852
TI  - Microstructure of colloidal dispersions in the ionic liquid ethylammonium
      nitrate: influence of the nature of the nanoparticles' counterion.
AB  - In order to better identify the key parameters governing colloidal stability in
      ionic liquids we probe the influence of the nature of the initial counterion of
      citrate-coated maghemite nanoparticles (NP), with Na(+), Li(+) and ethylammonium
      (EA(+)) on their dispersions in ethylammonium nitrate (EAN). Chemical analysis
      shows that sodium and lithium counterions remain at the nanoparticle surface
      after their transfer from water to EAN, despite their low concentration compared
      with EA(+). Macroscopically, all suspensions are stable over the range of volume
      fractions PhiNP tested (~ 1% to 8%). A microstructural study coupling small angle
      scattering and magneto-optic birefringence measurements shows that nanoparticles
      are perfectly dispersed with sodium counterions and interact through weak
      repulsions. Conversely, small clusters of a few nanoparticles are formed with
      lithium counterions, with the aggregation number increasing with PhiNP. However,
      such clusters are fragile; evidence that the attractions responsible for
      aggregation are of weak amplitude. Suspensions with EA(+) counterions show an
      intermediate behaviour. Our results demonstrate the determining role of initial
      counterions of the nanoparticles on the microstructure of colloidal dispersions
      in ionic liquids and therefore, the essential role of the interfacial zone
      between the solid and the liquid. 

PMID- 24919853
TI  - High quality Mn-doped (Na,K)NbO3 nanofibers for flexible piezoelectric
      nanogenerators.
AB  - Enhanced piezoelectric and energy-harvesting characteristics of Mn-doped
      (Na0.5K0.5)NbO3 (NKN) nanofibers have been investigated with actual fabrication
      of potential flexible nanogenerators. The electrospinning process of nanofibers
      has been initially optimized with the proper level of chelating agent and
      annealing temperature. High quality nanofibers are successfully obtained only by
      means of a certain level of doped-Mn, which incorporates into the NKN perovskite
      structure and facilitates significant grain growth. A single-particle-stacked
      structure along the direction of fiber length becomes more evident with
      increasing Mn content. An XPS analysis confirms that Mn exists in multivalent
      states of Mn(2+)/Mn(3+). The effective piezoelectric coefficient of the
      nanofibers is found to be enhanced by 5 times with Mn-doping up to 3 mol % as
      characterized by piezoelectric force microscopy. The resultant flexible
      nanogenerators on PES films have exhibited ~0.3 V output voltage and ~50 nA
      output current under a bending strain. 

PMID- 24919854
TI  - Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell
      cycle-dependent/independent anti-tumor activities alone/in combination with
      gemcitabine.
AB  - The G1 restriction point is critical for regulating the cell cycle and is
      controlled by the Rb pathway (CDK4/6-cyclin D1-Rb-p16/ink4a). This pathway is
      important because of its inactivation in a majority of human tumors. Transition
      through the restriction point requires phosphorylation of retinoblastoma protein
      (Rb) by CDK4/6, which are highly validated cancer drug targets. We present the
      identification and characterization of a potent CDK4/6 inhibitor, LY2835219.
      LY2835219 inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb
      phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its
      activity is specific for Rb-proficient cells. In vivo target inhibition studies
      show LY2835219 is a potent inhibitor of Rb phosphorylation, induces a complete
      cell cycle arrest and suppresses expression of several Rb-E2F-regulated proteins
      24 hours after a single dose. Oral administration of LY2835219 inhibits tumor
      growth in human tumor xenografts representing different histologies in tumor
      bearing mice. LY2835219 is effective and well tolerated when administered up to
      56 days in immunodeficient mice without significant loss of body weight or tumor
      outgrowth. In calu-6 xenografts, LY2835219 in combination with gemcitabine
      enhanced in vivo antitumor activity without a G1 cell cycle arrest, but was
      associated with a reduction of ribonucleotide reductase expression. These results
      suggest LY2835219 may be used alone or in combination with standard-of-care
      cytotoxic therapy. In summary, we have identified a potent, orally active small
      molecule inhibitor of CDK4/6 that is active in xenograft tumors. LY2835219 is
      currently in clinical development.

PMID- 24919856
TI  - Updated recommendations: an assessment of NICE clinical guidelines.
AB  - BACKGROUND: Updating is important to ensure clinical guideline (CG)
      recommendations remain valid. However, little research has been undertaken in
      this field. We assessed CGs produced by the National Institute for Health and
      Care Excellence (NICE) to identify and describe updated recommendations and to
      investigate potential factors associated with updating. Also, we evaluated the
      reporting and presentation of recommendation changes. METHODS: We performed a
      descriptive analysis of original and updated CGs and recommendations, and an
      assessment of presentation formats and methods for recording information. We
      conducted a case-control study, defining cases as original recommendations that
      were updated ('new-replaced' recommendations), and controls as original
      recommendations that were considered to remain valid ('not changed'
      recommendations). We performed a comparison of main characteristics between cases
      and controls, and we planned a multiple regression analysis to identify potential
      predictive factors for updating. RESULTS: We included nine updated CGs (1,306
      recommendations) and their corresponding original versions (1,106
      recommendations). Updated CGs included 812 (62%) recommendations 'not reviewed',
      368 (28.1%) 'new' recommendations, 104 (7.9%) 'amended' recommendations, and 25
      (1.9%) recommendations reviewed but unchanged. The presentation formats used to
      indicate the changes in recommendations varied widely across CGs. Changes in
      'amended', 'deleted', and 'new-replaced' recommendations (n = 296) were reported
      infrequently, mostly in appendices. These changes were recorded in 167 (56.4%)
      recommendations; and were explained in 81 (27.4%) recommendations. We retrieved a
      total of 7.1% (n = 78) case recommendations ('new-replaced') and 2.4% (n = 27)
      control recommendations ('not changed') in original CGs. The updates were mainly
      from 'Fertility CG', about 'gynaecology, pregnancy and birth' topic, and
      'treatment' or 'prevention' purposes. We did not perform the multiple regression
      analysis as originally planned due to the small sample of recommendations
      retrieved. CONCLUSION: Our study is the first to describe and assess updated CGs
      and recommendations from a national guideline program. Our results highlight the
      pressing need to standardise the reporting and presentation of updated
      recommendations and the research gap about the optimal way to present updates to
      guideline users. Furthermore, there is a need to investigate updating predictive
      factors.

PMID- 24919855
TI  - First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2,
      nf-kappaBeta and p70s6k, in patients with advanced solid tumors.
AB  - BACKGROUND: PBI-05204, a Nerium oleander extract (NOE) containing the cardiac
      glycoside oleandrin, inhibits the alpha-3 subunit of Na-K ATPase, as well as FGF
      2 export, Akt and p70S6K, hence attenuating mTOR activity. This first-in-human
      study determined the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of
      PBI-05204 in patients with advanced cancer. Methods Forty-six patients received
      PBI-05204 by mouth for 21 of 28 days (3 + 3 trial design). Dose was escalated
      100% using an accelerated titration design until grade 2 toxicity was observed.
      Plasma PK and mTOR effector (p70S6K and pS6) protein expressions were evaluated.
      Results Dose-limiting toxicities (grade 3 proteinuria, fatigue) were observed at
      dose level 8 (0.3383 mg/kg/day). Common possible drug-related adverse were
      fatigue (26 patients, 56.5%), nausea (19 patients, 41.3%) and diarrhea (15
      patients, 32.6 %). Electrocardiogram monitoring revealed grade 1 atrioventricular
      block (N = 10 patients) and grade 2 supraventricular tachycardia (N = 1). The MTD
      was DL7 (0.2255 mg/kg) where no toxicity of grade >= 3 was observed in seven
      patients treated. Seven patients (15%) had stable disease > 4 months. Mean peak
      oleandrin concentrations up to 2 ng/mL were achieved, with area under the curves
      6.6 to 25.5 MUg/L*hr and a half-life range of 5-13 h. There was an average 10%
      and 35% reduction in the phosphorylation of Akt and pS6 in PBMC samples in 36 and
      32 patients, respectively, tested between predose and 21 days of treatment.
      Conclusions PBI-05204 was well tolerated in heavily pretreated patients with
      advanced solid tumors. The recommended Phase II dose is 0.2255 mg/kg/day.

PMID- 24919858
TI  - Picket-fence polythiophene and its diblock copolymers that afford microphase
      separations comprising a stacked and an isolated polythiophene ensemble.
AB  - All-polythiophene diblock copolymers, comprising one unsheathed block and one
      fenced block, were synthesized through catalyst-transfer polycondensation. The
      unsheathed block self-assembles through pi-pi stacking, thereby inducing
      microphase separation. Consequently, we have succeeded in creating a microphase
      separation comprising an ensemble of stacked and isolated polythiophenes. This
      achievement could be extended to various unexplored applications as a result of
      the integration of the contrasting functions of the two blocks. 

PMID- 24919857
TI  - Hypoalbuminaemia is an independent predictor of poor outcome in metastatic
      Ewing's sarcoma family of tumours: a single institutional experience of 150 cases
      treated with uniform chemotherapy protocol.
AB  - AIMS: Data on metastatic Ewing's sarcoma family of tumours (ESFT) with uniform
      chemotherapy protocol are minimal. MATERIALS AND METHODS: This was a single
      institutional patient review of patients treated between June 2003 and November
      2011 and evaluated on an intent-to-treat analysis. All patients received uniform
      chemotherapy: neoadjuvant chemotherapy (NACT), surgery and/or radiotherapy as
      local treatment followed by adjuvant chemotherapy. Local treatment was offered if
      the patient achieved a complete response and/or a partial response at both the
      primary and the metastatic site. RESULTS: In total, 150/374 (40%) ESFT patients
      were metastatic, with a median age of 15 years (range: 2-50); a tumour diameter
      of 10 cm (range: 1.8-26). Most common metastatic sites were lung only (53; 35%),
      bone only (35; 23%) and combined bone/lung (25; 17%). Twenty patients underwent
      surgery; 55 patients received radical radiotherapy after NACT. After a median
      follow-up of 26.1 months (range: 1.6-101.6), 5 year event-free survival (EFS),
      overall survival and local control rate (LCR) were 9.1 +/- 3.3%, 16.9 +/- 5.2%
      and 31.8 +/- 7.9%, respectively. Univariate analysis showed serum albumin <=3.4
      g/dl (P < 0.001) to predict inferior EFS. Tumour size >8 cm (P = 0.05),
      haemoglobin <=10 g/dl (P = 0.04), hypoalbuminaemia (P = 0.003) and radical
      radiotherapy as local treatment (P = 0.03) predicted inferior overall survival.
      No factor significantly predicted LCR, although age <=15 years (P = 0.08) and
      radical radiotherapy as local treatment (P = 0.09) had a trend towards inferior
      LCR. Hypoalbuminaemia was the only prognostic factor to predict EFS on
      multivariate analysis. CONCLUSION: This was the largest study of metastatic ESFT
      from Asia and identified a unique prognostic factor. In view of dismal prognosis
      with conventional chemotherapy in metastatic ESFT with hypoalbuminaemia,
      palliative intent therapy may be a potential therapeutic alternative for this
      subgroup of patients, especially in resource-challenged situations.

PMID- 24919860
TI  - A single nucleotide polymorphism in fibronectin 1 determines tumor shape in
      colorectal cancer.
AB  - Depressed and flat surface lesions are not easy to identify with routine
      colonoscopies during screening for colorectal cancer (CRC). Identifying
      clinically relevant genes that influence tumor shape could be useful when
      screening for the presence of depressed lesions. Total RNA was extracted from
      tumor cells collected by laser microdissection from the primary lesions of 146
      CRC cases. Microarray analysis was performed to identify genes that were
      differentially expressed between depressed and elevated tumors. Single nucleotide
      polymorphism (SNP) analysis of genomic DNA from the peripheral blood of 67 CRC
      patients was then used to associate polymorphisms with the occurrence of
      depressed tumors. Microarray analysis revealed significantly higher expression of
      the fibronectin 1 (FN1) gene in 129 depressed-type tumors and lesions compared to
      17 elevated-type tumors. FN1-abundant CRC tumors were large with a significantly
      higher incidence of lymphatic permeation. SNP analysis indicated that 44 tumors
      with a GG genotype at SNP rs6707530 showed significantly higher FN1 expression
      than did 23 tumors with GT/TT genotypes (p<0.05). The product of the FN1 gene
      (located at 2q34) is involved in cell adhesion, migration and metastasis in
      mesenchymal tumors. Abundant expression of FN1 may allow cancer cells to invade
      deeper layers, which would eventually define tumor shape. Identification of this
      SNP in blood samples may facilitate disease diagnosis and allow prediction of the
      presence of depressed tumors in the colorectal epithelium before a colon
      fiberscope examination.

PMID- 24919861
TI  - Surveillance for low-grade dysplastic Barrett's oesophagus: one size fits all?
AB  - This paper reviews the role of low-grade dysplasia (LGD) as a marker of
      progression in Barrett's oesophagus (BO). Albeit with its limits due to the
      difficulty of its diagnosis and the low agreement among pathologists, LGD remains
      the most relevant single prognostic factor of progression, and, when the
      diagnosis is confirmed by two or three pathologists, the chances of progression
      to high-grade dysplasia or invasive adenocarcinoma are as high as 40%. On the
      other hand, BO patients who remain dysplasia free at several follow-up
      examinations seem to have a very low likelihood of progression. The diagnosis of
      LGD should be confirmed by two pathologists, and surveillance programs should be
      tailored depending on the presence or persistent absence of LGD. Ablative therapy
      should be also considered for cases where LGD persists in a series of follow-ups.

PMID- 24919862
TI  - Deferasirox: a review of its use for chronic iron overload in patients with non
      transfusion-dependent thalassaemia.
AB  - Deferasirox (Exjade((r))) is a once-daily orally administered iron chelator which
      has been approved for use in the treatment of transfusional-dependent chronic
      iron overload since 2005. Based primarily on the findings of the THALASSA
      (Assessment of Exjade((r)) in Non-Transfusion-Dependent THALASSemiA) trial, the
      approval for deferasirox has recently been expanded to include the management of
      chronic iron overload in patients with non-transfusion-dependent thalassaemia
      (NTDT) syndromes. Despite the lack of regular blood transfusions, NTDT patients
      can still develop clinically relevant iron overload, primarily due to increased
      gastrointestinal absorption secondary to ineffective erythropoiesis, and may
      require chelation therapy. The THALASSA trial, the first placebo-controlled
      clinical trial of an iron chelator in NTDT patients, demonstrated that
      deferasirox was effective in reducing liver iron and serum ferritin levels in
      this population. Deferasirox has an acceptable tolerability profile, with the
      most common adverse events reported in the THALASSA trial being related to mild
      to moderate gastrointestinal disorders. Although further long-term studies will
      be required to clearly demonstrate the clinical benefit of chelation therapy in
      NTDT patients, deferasirox presents a useful tool in the management of iron
      overload in this population. 

PMID- 24919863
TI  - Certolizumab pegol: a review of its use in patients with axial spondyloarthritis
      or psoriatic arthritis.
AB  - Certolizumab pegol (Cimzia((r))) is a polyethylene glycolylated antigen-binding
      fragment of a recombinant human monoclonal antibody that binds to and selectively
      neutralizes tumour necrosis factor (TNF) alpha. In the EU, subcutaneous
      certolizumab pegol is indicated for the treatment of adults with severe active
      axial spondyloarthritis (axSpA), comprising ankylosing spondylitis (AS) and non
      radiographic axSpA (nr-axSpA), and for adults with active psoriatic arthritis
      (PsA). In the USA it is indicated for the treatment of adults with active AS or
      active PsA. This article reviews the efficacy and tolerability of certolizumab
      pegol in these patients and briefly summarizes its pharmacology. In two ongoing,
      well-designed studies, data at 12 and 24 weeks showed that treatment with
      certolizumab pegol (200 mg every 2 weeks or 400 mg every 4 weeks) was effective
      in improving the clinical signs and symptoms of disease, health-related quality
      of life and productivity in patients with axSpA (the RAPID-axSpA study) or PsA
      (the RAPID-PsA study), with the improvements maintained during longer-term (48
      weeks) treatment. Within the axSpA population, clinical benefits with
      certolizumab pegol were seen both in patients with AS and in those with nr-axSpA.
      In addition, 12 weeks' treatment with certolizumab pegol reduced inflammation in
      the sacroiliac joints and spine in patients with axSpA and 24 weeks' treatment
      with the agent slowed radiographic disease progression in patients with PsA.
      Certolizumab pegol was generally well tolerated in these studies, with a
      tolerability profile consistent with that seen in previous clinical trials in
      other indications. Although additional long-term and comparative data are needed
      to position certolizumab pegol with respect to other TNFalpha antagonists,
      current evidence indicates that certolizumab pegol is an effective option for the
      treatment of axSpA (including AS and nr-axSpA) and PsA.

PMID- 24919864
TI  - Ustekinumab: a review of its use in psoriatic arthritis.
AB  - Ustekinumab (Stelara((r))) is a human monoclonal antibody that binds to the
      shared p40 subunit of interleukin (IL)-12 and IL-23, blocking signalling of their
      cognate receptors. It is established in the treatment of moderate-to-severe
      plaque psoriasis, but recently received approval in adults with active psoriatic
      arthritis. Tumour necrosis factor (TNF) inhibitors remain first-line biological
      agents for the treatment of psoriatic arthritis, but alternative agents are
      needed. This article summarises the pharmacology of ustekinumab and reviews its
      use in phase 3 trials in psoriatic arthritis. In these trials, subcutaneous
      ustekinumab 45 or 90 mg was significantly more effective than placebo, as
      determined by American College of Rheumatology response criteria at week 24. The
      drug was also associated with significantly greater efficacy than placebo with
      regard to secondary endpoints, including the Psoriasis Area and Severity Index >=
      75 % response, enthesitis and dactylitis scores, radiographic progression and
      Health Assessment Questionnaire-Disability Index scores. Response to ustekinumab
      was maintained during long-term therapy (up to week 100), and was achieved with
      and without concomitant methotrexate. Ustekinumab was generally well tolerated,
      and the tolerability profile in psoriatic arthritis was similar to that reported
      in plaque psoriasis. Throughout long-term ustekinumab treatment, serious
      infection or major cardiovascular adverse events occurred rarely. More data are
      needed to clearly define the place of ustekinumab in psoriatic arthritis
      treatment algorithms. Meanwhile the drug is a valuable additional option for
      patients with psoriatic arthritis in whom the response to previous non-biological
      disease-modifying antirheumatic drugs has been inadequate, or for those who have
      failed anti-TNF therapy.

PMID- 24919865
TI  - Self-association of oligothiophenes in isotropic systems.
AB  - The self-association equilibrium constants, Kass, for the dimerization of some
      small oligothiophenes in acetone, acetonitrile and chloroform were measured by
      (1)H NMR spectroscopy. The gas phase interaction energies for some oligothiophene
      dimers were determined by computational quantum chemistry. The (1)H NMR results
      indicate that Kass generally increases with the chain length (the number of
      thienyl rings, n) and solvent polarity; however, Kass for thiophene (n = 1) was
      found to be higher than for the bithiophenes (n = 2). The linear oligothiophenes
      2,2'-bithiophene and 2,2',5',2''-terthiophene were found to self-associate less
      than their corresponding nonlinear isomers 3,3'-bithiophene and 3,2',5',3''
      terthiophene in solution and in the gas phase. For alpha-quaterthiophene (n = 4)
      Kass in solution was found to be smaller than expected. The non-linear dependence
      of the standard molar Gibbs energy of self-association, DeltaassG, on the chain
      length in solution could be nicely reproduced and related to the conformational
      entropy change of dimerization. It was observed that the melting properties of
      oligothiophenes correlate well with their tendency to self-associate, with more
      self-association leading to increased liquid stability, and thus lower melting
      temperatures. These results highlight the relevance of self-association in
      isotropic systems for the correct molecular interpretation of phase equilibria. 

PMID- 24919866
TI  - Valve cuspidity: a risk factor for aortic valve repair?
AB  - BACKGROUND: The aim of this study was to analyze short- and mid-term results
      after aortic valve (AV) repair with particular regard to the impact of valve
      cuspidity (bicuspid versus tricuspid aortic valve). METHODS: One hundred patients
      with aortic regurgitation (AR) undergoing aortic valve repair between November
      2007 and October 2012 were included in the study. Sixty patients had bicuspid AV
      (BAV group; 11 females) and 40 patients had tricuspid AV (TAV group; 13 females).
      AR > grade 2 was present in 47 (78%) patients in the BAV and in 35 (88%) patients
      in the TAV group. Follow-up was complete in 100% and median was 25 months.
      RESULTS: Isolated aortic valve repair was performed in 27 (45%) of BAV patients
      and in six (15%) of TAV patients. Replacement of the ascending aorta and/or
      aortic root was performed in 33 (55%) of BAV patients and in 34 (86%) of TAV
      patients. There was no death within 30 days postoperatively, while two patients
      died (TAV group) during the follow-up period. There was no statistical difference
      between BAV and TAV groups with regard to the survival (100 +/- 0% vs. 95 +/- 4%,
      p = 0.102), the three-year freedom from AV-related reoperation (90 +/- 5% vs. 89
      +/- 6%, p = 0.456), and the three-year freedom from AR grade > 2 (86 +/- 6% vs.
      82 +/- 7%, p = 0.866), respectively. CONCLUSIONS: This study demonstrates no
      difference in mid-term results after regurgitant bicuspid and tricuspid aortic
      valve repair, suggesting that bicuspid valve may not be a risk factor for aortic
      valve repair.

PMID- 24919867
TI  - A multiple imputation strategy for sequential multiple assignment randomized
      trials.
AB  - Sequential multiple assignment randomized trials (SMARTs) are increasingly being
      used to inform clinical and intervention science. In a SMART, each patient is
      repeatedly randomized over time. Each randomization occurs at a critical decision
      point in the treatment course. These critical decision points often correspond to
      milestones in the disease process or other changes in a patient's health status.
      Thus, the timing and number of randomizations may vary across patients and depend
      on evolving patient-specific information. This presents unique challenges when
      analyzing data from a SMART in the presence of missing data. This paper presents
      the first comprehensive discussion of missing data issues typical of SMART
      studies: we describe five specific challenges and propose a flexible imputation
      strategy to facilitate valid statistical estimation and inference using
      incomplete data from a SMART. To illustrate these contributions, we consider data
      from the Clinical Antipsychotic Trial of Intervention and Effectiveness, one of
      the most well-known SMARTs to date.

PMID- 24919869
TI  - Fermentation of Smilax china root by Aspergillus usami and Saccharomyces
      cerevisiae promoted concentration of resveratrol and oxyresveratrol and the free
      radical scavenging activity.
AB  - BACKGROUND: Smilax china root, which is rich in resveratrol and oxyresveratrol,
      has been used as emergency foods as well as folk medicine. This study
      investigated changes in concentration of bioactive components and the free
      radical scavenging capacity of Smilax china root during fermentation by
      Aspergillus usami and Saccharomyces cerevisiae. RESULTS: Resveratrol,
      oxyresveratrol and piceid were quantified as major constituents in Smilax china
      root by using UPLC-ESI-MS. The concentration of oxyresveratrol and resveratrol
      remarkably increased through fermentation and the transformation of piceid to
      resveratrol. Its concentration in 4% Smilax china root was 1.16-2.95 times higher
      than that of a 2% preparation throughout fermentation. The vitamin C equivalent
      antioxidant capacity of 2% Smilax china root was 1.51-1.91 times higher than that
      of 4% Smilax china root during fermentation. Meanwhile, ABTS free-radical
      scavenging capacity was enhanced up to 95.07 and 99.35% for 2% and 4% Smilax
      china root, respectively. CONCLUSION: Results from our study propose that
      bioactive components in Smilax China root were highly extracted by fermentation
      followed by saccharification and ethanol production, resulting in enhanced free
      radical scavenging capacity. (c) 2013 Society of Chemical Industry.

PMID- 24919868
TI  - The complete genome sequences of poxviruses isolated from a penguin and a pigeon
      in South Africa and comparison to other sequenced avipoxviruses.
AB  - BACKGROUND: Two novel avipoxviruses from South Africa have been sequenced, one
      from a Feral Pigeon (Columba livia) (FeP2) and the other from an African penguin
      (Spheniscus demersus) (PEPV). We present a purpose-designed bioinformatics
      pipeline for analysis of next generation sequence data of avian poxviruses and
      compare the different avipoxviruses sequenced to date with specific emphasis on
      their evolution and gene content. RESULTS: The FeP2 (282 kbp) and PEPV (306 kbp)
      genomes encode 271 and 284 open reading frames respectively and are more closely
      related to one another (94.4%) than to either fowlpox virus (FWPV) (85.3% and
      84.0% respectively) or Canarypox virus (CNPV) (62.0% and 63.4% respectively).
      Overall, FeP2, PEPV and FWPV have syntenic gene arrangements; however, major
      differences exist throughout their genomes. The most striking difference between
      FeP2 and the FWPV-like avipoxviruses is a large deletion of ~16 kbp from the
      central region of the genome of FeP2 deleting a cc-chemokine-like gene, two
      Variola virus B22R orthologues, an N1R/p28-like gene and a V-type Ig domain
      family gene. FeP2 and PEPV both encode orthologues of vaccinia virus C7L and
      Interleukin 10. PEPV contains a 77 amino acid long orthologue of Ubiquitin
      sharing 97% amino acid identity to human ubiquitin. CONCLUSIONS: The genome
      sequences of FeP2 and PEPV have greatly added to the limited repository of
      genomic information available for the Avipoxvirus genus. In the comparison of
      FeP2 and PEPV to existing sequences, FWPV and CNPV, we have established insights
      into African avipoxvirus evolution. Our data supports the independent evolution
      of these South African avipoxviruses from a common ancestral virus to FWPV and
      CNPV.

PMID- 24919870
TI  - Pharmacogenetics role in the safety of acenocoumarol therapy.
AB  - Vitamin K antagonists (VKAs) remain as the most prescribed drug for treatment and
      prevention of thrombotic disorders in many countries, despite the recent approval
      of the new oral anticoagulants (NOACs). Although effectiveness and safety of VKAs
      are tightly associated to maintaining the patient within the international
      normalised ratio (INR) therapeutic range (TWR), they have been likened to NOACs
      when patients are in good INR control (>=66% of TWR). Therefore, assessing the
      safety of patients should be a priority in the selection of the anticoagulation
      therapy. The aim of this study was to evaluate the association between CYP2C9*2,
      CYP2C9*3, VKORC1, CYP4F2*3, ABCB1 C3435T, APOE, CYP2C19*2 and CYP2C19*17 gene
      polymorphisms and treatment safety in 128 patients diagnosed with atrial
      fibrillation or venous thromboembolism during the initial first seven months of
      acenocoumarol therapy. After the first month, VKORC1-T-allele and APOE-E3/E3
      genotype were independently associated to higher time above therapeutic range
      (TAR) and lower time below the therapeutic range (TBR). After seven months,
      VKORC1 T-allele predicted higher TAR, and was also associated to increased INR>4,
      particularly the TT-genotype (odds ratio [OR]: 32; 95% confidence interval
      [CI95%]: 6-175; p=810-5). C-alleles for CYP2C9*3 (OR: 5.5; CI95%: 1.8-17;
      p=0.003) and ABCB1 (OR: 8.9;CI95%: 1.1-70; p=0.039) independently influenced on
      INR>6 . Patients VKORC1-TT/ABCB1-C remained 26.8% [19.7-38.9] TAR, with
      associated relative risk (RR) for INR>4 1.8 higher (CI95%: 1.2-2.5; p=0.015).
      Patients VKORC1-TT also presented the highest risk of bleeding events (RR:
      3.5;CI95%: 1.4-8.4; p=0,010). In conclusion, VKORC1, CYP2C9*3, APOE and ABCB1
      genotypes should be considered in prevention of overanticoagulation and bleeding
      events in the initiation of acenocoumarol therapy. 

PMID- 24919871
TI  - Autophagy activation and antiviral activity by a licorice triterpene.
AB  - The triterpene glycyrrhizic acid (GRA), the main product from the Glycyrrhiza
      glabra medicinal plant, is known for its antiinflammatory and antimicrobial
      activity. In this work, GRA was studied for its ability to induce the autophagic
      process activator Beclin 1 in epithelial cells and to observe how this property
      could influence its antiviral activity. After 24 h of treatment, GRA induced a
      Beclin 1 production that was more than twofold higher than that produced by
      rapamycin, used as a reference compound. When the compounds were added to HeLa
      cells together with the viruses, GRA demonstrated a strong antiherpes simplex
      virus type 1 (HSV1) activity, whereas rapamycin had no activity. However, if the
      compounds were added to the cells 24 h before the viruses, GRA induced the
      production of an even higher amount of Beclin 1 and showed an improved antiviral
      effect; under these conditions, rapamycin was also able to exert a significant
      anti-HSV1 activity. In conclusion, GRA is a strong inducer of the autophagy
      activator Beclin 1, which establishes a resistance state to HSV1 replication.

PMID- 24919872
TI  - An investigation of the use of discriminant analysis for the classification of
      blade edge type from cut marks made by metal and bamboo blades.
AB  - Analysis of cut marks in bone is largely limited to two dimensional qualitative
      description. Development of morphological classification methods using
      measurements from cut mark cross sections could have multiple uses across
      palaeoanthropological and archaeological disciplines, where cutting edge types
      are used to investigate and reconstruct behavioral patterns. An experimental
      study was undertaken, using porcine bone, to determine the usefulness of
      discriminant function analysis in classifying cut marks by blade edge type, from
      a number of measurements taken from their cross-sectional profile. The
      discriminant analysis correctly classified 86.7% of the experimental cut marks
      into serrated, non-serrated and bamboo blade types. The technique was then used
      to investigate a series of cut marks of unknown origin from a collection of
      trophy skulls from the Torres Strait Islands, to investigate whether they were
      made by bamboo or metal blades. Nineteen out of twenty of the cut marks
      investigated were classified as bamboo which supports the non-contemporaneous
      ethnographic accounts of the knives used for trophy taking and defleshing
      remains. With further investigation across a variety of blade types, this
      technique could prove a valuable tool in the interpretation of cut mark evidence
      from a wide variety of contexts, particularly in forensic anthropology where the
      requirement for presentation of evidence in a statistical format is becoming
      increasingly important.

PMID- 24919873
TI  - A Fellow's perspective on the threatened closure of the Illinois Poison Center.

PMID- 24919874
TI  - Mechanically resolving noncovalent bonds using acoustic radiation force.
AB  - The resolution of molecular bonds and subsequent selective control of their
      binding are of great significance in chemistry and biology. We have developed a
      method based on the use of acoustic radiation force to precisely dissociate
      noncovalent molecular bonds. The acoustic radiation force is produced by
      extremely low-power ultrasound waves and is mediated by magnetic particles. We
      successfully distinguished the binding of antibodies of different subclasses and
      the binding of DNA duplexes with a single-base-pair difference. In contrast to
      most ultrasound applications in chemistry, the sonication probe is noninvasive
      and requires a sample volume of only a few microliters. Our method is thus viable
      for noninvasive and accurate control of molecular bonds that are widely
      encountered in biochemistry. 

PMID- 24919875
TI  - Young woman with massive splenomegaly.

PMID- 24919876
TI  - Ring opening and bidentate coordination of amidinate germylenes and silylenes on
      carbonyl dicobalt complexes: the importance of a slight difference in ligand
      volume.
AB  - The reactions of [Co2 (CO)8 ] with one equiv of the benzamidinate (R2 bzam) group
      14 tetrylenes [M(R2 bzam)(HMDS)] (HMDS=N(SiMe3 )2 ; 1: M=Ge, R=iPr; 2: M=Si,
      R=tBu; 3: M=Ge, R=tBu) at 20  degrees C led to the monosubstituted complexes [Co2
      {kappa(1) M?M(R2 bzam)(HMDS)}(CO)7 ] (4: M=Ge, R=iPr; 5: M=Si, R=tBu; 6: M=Ge,
      R=tBu), which contain a terminal kappa(1) M-tetrylene ligand. Whereas the Co2 Si
      and Co2 Ge tert-butyl derivatives 5 and 6 are stable at 20  degrees C, the Co2 Ge
      isopropyl derivative 4 evolved to the ligand-bridged derivative [Co2 {MU-kappa(2)
      Ge,N-Ge(iPr2 bzam)(HMDS)}(MU-CO)(CO)5 ] (7), in which the Ge atom spans the Co?Co
      bond and one arm of the amidinate fragment is attached to a Co atom. The
      mechanism of this reaction has been modeled with the help of DFT calculations,
      which have also demonstrated that the transformation of amidinate-tetrylene
      ligands on the dicobalt framework is negligibly influenced by the nature of the
      group-14 metal atom (Si or Ge) but is strongly dependent upon the volume of the
      amidinate N?R groups. The disubstituted derivatives [Co2 {kappa(1) M?M(R2
      bzam)(HMDS)}2 (CO)6 ] (8: M=Ge, R=iPr; 9: M=Si, R=tBu; 10: M=Ge, R=tBu), which
      contain two terminal kappa(1) M-tetrylene ligands, have been prepared by treating
      [Co2 (CO)8 ] with two equiv of 1-3 at 20  degrees C. The IR spectra of 8-10 have
      shown that the basicity of germylenes 1 and 3 is very high (comparable to that of
      trialkylphosphanes and 1,3-diarylimidazol-2-ylidenes), whereas that of silylene 2
      is even higher. 

PMID- 24919877
TI  - Meaningfulness of mean group results for determining the optimal motor
      rehabilitation program for an individual child with cerebral palsy.
AB  - As research on the efficacy or effectiveness of interventions to improve motor
      functioning in cerebral palsy (CP) has accumulated and been incorporated into
      systematic reviews, the foundation for evidence-based practice in CP is growing.
      To determine whether an intervention is effective, clinical trials report mean
      group differences. However, even if a statistically significant mean group effect
      is found, this does not imply that this intervention was effective for each study
      participant or ensure positive outcomes for all with CP. A personalized approach
      to medical care is currently being advocated based primarily on increasingly
      recognized genetic variations in individual responses to medications and other
      therapies. A similar approach is also warranted, and perhaps more justifiable, in
      CP which includes a heterogeneous group of disorders. Even interventions deemed
      highly effective in CP demonstrate a range of individual responses along a
      continuum from a negative or negligible response to a strong positive effect, the
      bases for which remain incompletely understood. This narrative review recommends
      that the next critical step in advancing evidence-based practice is to implement
      research strategies to identify patient factors that predict treatment responses
      so we can not only answer the question 'what works', but also 'what works best,
      for whom'. 

PMID- 24919878
TI  - Network-guided regression for detecting associations between DNA methylation and
      gene expression.
AB  - MOTIVATION: High-throughput profiling in biological research has resulted in the
      availability of a wealth of data cataloguing the genetic, epigenetic and
      transcriptional states of cells. These data could yield discoveries that may lead
      to breakthroughs in the diagnosis and treatment of human disease, but require
      statistical methods designed to find the most relevant patterns from millions of
      potential interactions. Aberrant DNA methylation is often a feature of cancer,
      and has been proposed as a therapeutic target. However, the relationship between
      DNA methylation and gene expression remains poorly understood. RESULTS: We
      propose Network-sparse Reduced-Rank Regression (NsRRR), a multivariate regression
      framework capable of using prior biological knowledge expressed as gene
      interaction networks to guide the search for associations between gene expression
      and DNA methylation signatures. We use simulations to show the advantage of our
      proposed model in terms of variable selection accuracy over alternative models
      that do not use prior network information. We discuss an application of NsRRR to
      The Cancer Genome Atlas datasets on primary ovarian tumours. AVAILABILITY AND
      IMPLEMENTATION: R code implementing the NsRRR model is available at
      http://www2.imperial.ac.uk/~gmontana CONTACT: giovanni.montana@kcl.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24919879
TI  - Blue: correcting sequencing errors using consensus and context.
AB  - MOTIVATION: Bioinformatics tools, such as assemblers and aligners, are expected
      to produce more accurate results when given better quality sequence data as their
      starting point. This expectation has led to the development of stand-alone tools
      whose sole purpose is to detect and remove sequencing errors. A good error
      correcting tool would be a transparent component in a bioinformatics pipeline,
      simply taking sequence data in any of the standard formats and producing a higher
      quality version of the same data containing far fewer errors. It should not only
      be able to correct all of the types of errors found in real sequence data
      (substitutions, insertions, deletions and uncalled bases), but it has to be both
      fast enough and scalable enough to be usable on the large datasets being produced
      by current sequencing technologies, and work on data derived from both haploid
      and diploid organisms. RESULTS: This article presents Blue, an error-correction
      algorithm based on k-mer consensus and context. Blue can correct substitution,
      deletion and insertion errors, as well as uncalled bases. It accepts both FASTQ
      and FASTA formats, and corrects quality scores for corrected bases. Blue also
      maintains the pairing of reads, both within a file and between pairs of files,
      making it compatible with downstream tools that depend on read pairing. Blue is
      memory efficient, scalable and faster than other published tools, and usable on
      large sequencing datasets. On the tests undertaken, Blue also proved to be
      generally more accurate than other published algorithms, resulting in more
      accurately aligned reads and the assembly of longer contigs containing fewer
      errors. One significant feature of Blue is that its k-mer consensus table does
      not have to be derived from the set of reads being corrected. This decoupling
      makes it possible to correct one dataset, such as small set of 454 mate-pair
      reads, with the consensus derived from another dataset, such as Illumina reads
      derived from the same DNA sample. Such cross-correction can greatly improve the
      quality of small (and expensive) sets of long reads, leading to even better
      assemblies and higher quality finished genomes. AVAILABILITY AND IMPLEMENTATION:
      The code for Blue and its related tools are available from
      http://www.bioinformatics.csiro.au/Blue. These programs are written in C# and run
      natively under Windows and under Mono on Linux.

PMID- 24919880
TI  - Predicting dynamic signaling network response under unseen perturbations.
AB  - MOTIVATION: Predicting trajectories of signaling networks under complex
      perturbations is one of the most valuable, but challenging, tasks in systems
      biology. Signaling networks are involved in most of the biological pathways, and
      modeling their dynamics has wide applications including drug design and treatment
      outcome prediction. RESULTS: In this paper, we report a novel model for
      predicting the cell type-specific time course response of signaling proteins
      under unseen perturbations. This algorithm achieved the top performance in the
      2013 8th Dialogue for Reverse Engineering Assessments and Methods (DREAM 8)
      subchallenge: time course prediction in breast cancer cell lines. We formulate
      the trajectory prediction problem into a standard regularization problem; the
      solution becomes solving this discrete ill-posed problem. This algorithm includes
      three steps: denoising, estimating regression coefficients and modeling
      trajectories under unseen perturbations. We further validated the accuracy of
      this method against simulation and experimental data. Furthermore, this method
      reduces computational time by magnitudes compared to state-of-the-art methods,
      allowing genome-wide modeling of signaling pathways and time course trajectories
      to be carried out in a practical time. AVAILABILITY AND IMPLEMENTATION: Source
      code is available at http://guanlab.ccmb.med.umich.edu/DREAM/code.html and as
      supplementary file online.

PMID- 24919881
TI  - Short rest periods between work shifts predict sleep and health problems in
      nurses at 1-year follow-up.
AB  - OBJECTIVES: We investigated whether the number of work shifts separated by less
      than 11 hours (quick returns) at baseline (T1) could predict health problems in
      nurses at 1-year follow-up (T2). METHODS: 1224 nurses responded to a
      questionnaire-based survey in 2009 (T1) and 2010 (T2). Crude and adjusted
      logistic regression analyses were completed to assess the association between
      annual number of quick returns at T1 and the following outcome variables at T2:
      shift work disorder (SWD), excessive sleepiness (Epworth Sleepiness Scale),
      pathological fatigue (Chalder Fatigue Scale) and anxiety and depression (Hospital
      Anxiety and Depression Scale), while controlling for age, gender, the
      corresponding outcome variable at T1, number of night shifts at T1, change in
      number of quick returns and number of night shifts from T1 to T2. RESULTS: The
      adjusted analyses showed that the annual number of quick returns at T1 predicted
      the occurrence of SWD (OR=1.01, 95% CI 1.00 to 1.01) and pathological fatigue
      (OR=1.01, 95% CI 1.00 to 1.01) at T2. A decreased number of quick returns from T1
      to T2 entailed a reduced risk of pathological fatigue (OR=0.67, 95% CI 0.45 to
      0.99) at T2. There was no association between quick returns at T1 and excessive
      sleepiness, anxiety or depression at T2 in the adjusted analyses. CONCLUSIONS:
      This is the first longitudinal study investigating the associations between quick
      returns and future health problems. Quick returns increased the risk of SWD and
      pathological fatigue at 1-year follow-up. Reducing the number of quick returns
      from 1 year to the next was related to reduced risk of developing pathological
      fatigue.

PMID- 24919882
TI  - Intracisternal injection of palmitoylethanolamide inhibits the peripheral
      nociceptive evoked responses of dorsal horn wide dynamic range neurons.
AB  - Endogenous palmitoylethanolamide (PEA) has a key role in pain modulation. Central
      or peripheral PEA can reduce nociceptive behavior, but no study has yet reported
      a descending inhibitory effect on the neuronal nociceptive activity of Adelta-
      and C-fibers. This study shows that intracisternal PEA inhibits the peripheral
      nociceptive responses of dorsal horn wide dynamic range cells (i.e., inhibition
      of Adelta- and C-fibers), an effect blocked by spinal methiothepin. These results
      suggest that a descending analgesic mechanism mediated by the serotonergic system
      could be activated by central PEA. 

PMID- 24919884
TI  - The Sensory World of Fish and Fisheries: The Impact of Human Activities.
AB  - This special issue of Integrative Zoology (the official journal of the
      International Society of Zoological Sciences and the Institute of Zoology,
      Chinese Academy of Sciences) is dedicated to the sensory world of fish and
      fisheries and the impacts of human activities. The papers in this issue are the
      outcome of an international conference that was held at the Institute of Marine
      Biosystem and Neurosciences, College of Fisheries and Life Science, Shanghai
      Ocean University, Shanghai, China from October 29 to November 1, 2012. The
      conference was generously sponsored by The Shanghai Ocean University, The
      University of Maryland, and The University of Western Australia. As co-organisers
      of this international meeting we are indebted to the former president of the
      Shanghai Ocean University, President Yingjie Pan and the other members of the
      organising Committee for their generous support to enable leading scientists in
      the fields of sensory ecology, behaviour, environmental management and fisheries
      science from both China and overseas to join the meeting and contribute to this
      issue. This article is protected by copyright. All rights reserved.

PMID- 24919885
TI  - Effect of cation symmetry on the organization of ionic liquids near a charged
      mica surface.
AB  - Atomistic molecular dynamics simulations have been carried out to understand the
      effect of the symmetry of cations on the microscopic organization of ionic
      liquids near a charged mica surface. Ionic liquids with a 1,3-alkylimidazolium
      ([C(n)C(m)im](+)) cation and a bis(trifluoromethylsulfonyl)imide ([NTf2](-))
      anion were investigated. Apart from symmetry, the length of the alkyl group
      attached to the cation is found to crucially determine the ion structure near the
      solid surface. In the first adsorbed layer, the ring planes of cations with
      shorter alkyl groups (less than four carbon atoms) are oriented either parallel
      or perpendicular to the surface. However, cations with longer alkyl tails are
      exclusively observed to have their ring planes parallel to the mica surface. The
      alkyl groups too show a similar dependence of their orientation on the tail
      length. Further, symmetric cations with alkyl groups of intermediate length are
      more highly structured at the interface than their asymmetric counterparts.

PMID- 24919883
TI  - Lipopolysaccharide treatment arrests the cell cycle of BV-2 microglial cells in
      G1 phase and protects them from UV light-induced apoptosis.
AB  - We previously reported that an optimal dose of lipopolysaccharide (LPS) markedly
      extends the lifespan of murine primary-cultured microglia by suppressing cell
      death pathways. In this study, we investigated the effects of LPS pretreatment on
      UV light-induced apoptosis of cells from the microglial cell line BV-2. More than
      half of BV-2 cells were apoptotic, and procaspase-3 was cleaved into its active
      form at 3 h of UV irradiation. In contrast, in BV-2 cells treated with LPS for 24
      h, UV irradiation caused neither apoptosis nor procaspase-3 cleavage. LPS
      treatment arrested the cell cycle in G1 phase and upregulated cyclin-dependent
      kinase inhibitor p21(Waf1/Cip1) and growth arrest and DNA damage-inducible (GADD)
      45alpha in BV-2 cells. When p21(Waf1/Cip1) and GADD45alpha were knocked down by
      small interfering RNA, procaspase-3 was cleaved into its active form to induce
      apoptosis. Our findings suggest that LPS inhibits UV-induced apoptosis in BV-2
      cells through arrest of the cell cycle in G1 phase by upregulation of
      p21(Waf1/Cip1) and GADD45alpha. Excessive activation of microglia may play a
      critical role in the exacerbation of neurodegeneration, therefore, normalizing
      the precise regulation of apoptosis may be a new strategy to prevent the
      deterioration caused by neurodegenerative disorders. 

PMID- 24919887
TI  - Desogestrel versus danazol as preoperative treatment for hysteroscopic surgery: a
      prospective, randomized evaluation.
AB  - The aim of this single-center, prospective, randomized, parallel-group study was
      to compare desogestrel and danazol as preoperative endometrial preparation for
      hysteroscopic surgery. We enrolled 200 consecutive eligible patients, in
      reproductive age, with endouterine diseases. Pre- and post-treatment
      characterization of endometrium was performed by hysteroscopic visual observation
      and histologic confirmation. The enrolled patients were randomly assigned to two
      groups: 100 were treated with 75 MUg of desogestrel/die, 100 with 100 mg of
      danazol/die, both orally for 5 weeks, starting on Day 1 of menstruation. We
      recorded intraoperative data (cervical dilatation time, operative time, infusion
      volume and severity of bleeding) and drugs' side effects. Post-treatment
      comparison of endometrial patterns showed a significant more marked effect of
      desogestrel, respect to danazol, in atrophying endometrium ("normotrophic non
      responders" versus "hypotrophic"-"atrophic", p = 0.031). Intraoperative data
      showed no significant differences between the two groups for cervical dilatation
      time (p = 0.160), while in the desogestrel group we found a significant reduction
      of operative time (p = 0.020), infusion volume (p = 0.012), and severity of
      bleeding (p = 0.004). Moreover, desogestrel caused less side effects (p = 0.031).
      According to our data analysis, desogestrel showed most marked effect in inducing
      endometrial atrophy, allowed a better intraoperative management and caused less
      side effects during treatment.

PMID- 24919886
TI  - Independent and combined influence of neonatal and current body composition on
      academic performance in youth: The UP & DOWN Study.
AB  - BACKGROUNDS: Unhealthy body composition is a cause for concern across the
      lifespan. OBJECTIVE: The objective of this study was to examine the independent
      and combined associations between neonatal and current body composition with
      academic performance among youth. METHODS: This cross-sectional study was
      conducted with a total of 1557 youth (745 girls) aged 10.4 +/- 3.4 years. Birth
      weight and length at birth were self-reported. Current body composition was
      assessed by body mass index (BMI), waist circumference (WC) and percentage of
      body fat (BF%). Academic performance was assessed through schools records.
      RESULTS: Birth weight was related to all academic variables in boys, independent
      of potential confounders, including BMI; whereas WC, BMI and BF% were related to
      all academic performance indicators in both boys and girls, independent of
      potential confounders, including birth weight (all P < 0.05). In addition, the
      combined adverse effects of low birth weight and current overweight on academic
      performance were observed in both boys and girls for grade point average (GPA)
      indicator. Boys in the group with none adverse effect had significantly higher
      scores in GPA (score +0.535; 95% confidence interval, 0.082-0.989) than boys in
      the group of both adverse effects (P < 0.007); among girls, GPA score was higher
      in the group with none adverse effect than in the groups with one or two adverse
      effects (P for trend = 0.029). CONCLUSIONS: Neonatal and current body
      composition, both independently and combined, may influence academic performance
      in youth.

PMID- 24919888
TI  - Jordan's stem-cell law can guide the Middle East.

PMID- 24919900
TI  - Fetal-cell revival for Parkinson's.

PMID- 24919901
TI  - Space-station science ramps up.

PMID- 24919902
TI  - Cancer-gene data sharing boosted.

PMID- 24919903
TI  - Sound clue in hunt for MH370.

PMID- 24919905
TI  - Stars of South American science.

PMID- 24919906
TI  - The impact gap: South America by the numbers.

PMID- 24919907
TI  - South American science: Big players.

PMID- 24919908
TI  - Research training: Homeward bound.

PMID- 24919910
TI  - Q&A: The nutrient hunter.

PMID- 24919911
TI  - Library science: Forgotten founder of bibliometrics.

PMID- 24919912
TI  - Academia and industry: Successes for UK cancer partnership.

PMID- 24919913
TI  - Alfred Russel Wallace: An early champion of women's rights.

PMID- 24919914
TI  - Synthetic biology: Missing the point.

PMID- 24919915
TI  - Synthetic biology: A global approach.

PMID- 24919916
TI  - Materials science: Diamond gets harder.

PMID- 24919917
TI  - Plant biology: Pass the ammunition.

PMID- 24919918
TI  - Two gamma-ray bursts from dusty regions with little molecular gas.
AB  - Long-duration gamma-ray bursts are associated with the explosions of massive
      stars and are accordingly expected to reside in star-forming regions with
      molecular gas (the fuel for star formation). Previous searches for carbon
      monoxide (CO), a tracer of molecular gas, in burst host galaxies did not detect
      any emission. Molecules have been detected as absorption in the spectra of gamma
      ray burst afterglows, and the molecular gas is similar to the translucent or
      diffuse molecular clouds of the Milky Way. Absorption lines probe the
      interstellar medium only along the line of sight, so it is not clear whether the
      molecular gas represents the general properties of the regions where the bursts
      occur. Here we report spatially resolved observations of CO line emission and
      millimetre-wavelength continuum emission in two galaxies hosting gamma-ray
      bursts. The bursts happened in regions rich in dust, but not particularly rich in
      molecular gas. The ratio of molecular gas to dust (<9-14) is significantly lower
      than in star-forming regions of the Milky Way and nearby star-forming galaxies,
      suggesting that much of the dense gas where stars form has been dissipated by
      other massive stars. 

PMID- 24919919
TI  - Nanotwinned diamond with unprecedented hardness and stability.
AB  - Although diamond is the hardest material for cutting tools, poor thermal
      stability has limited its applications, especially at high temperatures.
      Simultaneous improvement of the hardness and thermal stability of diamond has
      long been desirable. According to the Hall-Petch effect, the hardness of diamond
      can be enhanced by nanostructuring (by means of nanograined and nanotwinned
      microstructures), as shown in previous studies. However, for well-sintered
      nanograined diamonds, the grain sizes are technically limited to 10-30 nm (ref.
      3), with degraded thermal stability compared with that of natural diamond. Recent
      success in synthesizing nanotwinned cubic boron nitride (nt-cBN) with a twin
      thickness down to ~3.8 nm makes it feasible to simultaneously achieve smaller
      nanosize, ultrahardness and superior thermal stability. At present, nanotwinned
      diamond (nt-diamond) has not been fabricated successfully through direct
      conversions of various carbon precursors (such as graphite, amorphous carbon,
      glassy carbon and C60). Here we report the direct synthesis of nt-diamond with an
      average twin thickness of ~5 nm, using a precursor of onion carbon nanoparticles
      at high pressure and high temperature, and the observation of a new monoclinic
      crystalline form of diamond coexisting with nt-diamond. The pure synthetic bulk
      nt-diamond material shows unprecedented hardness and thermal stability, with
      Vickers hardness up to ~200 GPa and an in-air oxidization temperature more than
      200  degrees C higher than that of natural diamond. The creation of nanotwinned
      microstructures offers a general pathway for manufacturing new advanced carbon
      based materials with exceptional thermal stability and mechanical properties. 

PMID- 24919920
TI  - Increased frequency of extreme Indian Ocean Dipole events due to greenhouse
      warming.
AB  - The Indian Ocean dipole is a prominent mode of coupled ocean-atmosphere
      variability, affecting the lives of millions of people in Indian Ocean rim
      countries. In its positive phase, sea surface temperatures are lower than normal
      off the Sumatra-Java coast, but higher in the western tropical Indian Ocean.
      During the extreme positive-IOD (pIOD) events of 1961, 1994 and 1997, the eastern
      cooling strengthened and extended westward along the equatorial Indian Ocean
      through strong reversal of both the mean westerly winds and the associated
      eastward-flowing upper ocean currents. This created anomalously dry conditions
      from the eastern to the central Indian Ocean along the Equator and atmospheric
      convergence farther west, leading to catastrophic floods in eastern tropical
      African countries but devastating droughts in eastern Indian Ocean rim countries.
      Despite these serious consequences, the response of pIOD events to greenhouse
      warming is unknown. Here, using an ensemble of climate models forced by a
      scenario of high greenhouse gas emissions (Representative Concentration Pathway
      8.5), we project that the frequency of extreme pIOD events will increase by
      almost a factor of three, from one event every 17.3 years over the twentieth
      century to one event every 6.3 years over the twenty-first century. We find that
      a mean state change--with weakening of both equatorial westerly winds and
      eastward oceanic currents in association with a faster warming in the western
      than the eastern equatorial Indian Ocean--facilitates more frequent occurrences
      of wind and oceanic current reversal. This leads to more frequent extreme pIOD
      events, suggesting an increasing frequency of extreme climate and weather events
      in regions affected by the pIOD.

PMID- 24919922
TI  - Bushen-Yizhi formula ameliorates cognition deficits and attenuates oxidative
      stress-related neuronal apoptosis in scopolamine-induced senescence in mice.
AB  - Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula consisting of
      six herbs has been reported to possess a neuroprotective effect. The present
      study aimed to investigate the effects of BSYZ on learning and memory abilities,
      as well as oxidative stress and neuronal apoptosis in the hippocampus of
      scopolamine (SCOP)-induced senescence in mice, in order to reveal whether BSYZ is
      a potential therapeutic agent for Alzheimer's disease (AD). A high-performance
      liquid chromatography (HPLC) fingerprint was applied to provide a chemical
      profile of BSYZ. Extracts of BSYZ were orally administered to mice with SCOP
      induced memory impairment for two weeks. The learning and memory abilities were
      determined by the Morris water maze test. The oxidant stress-related indices,
      such as activity of superoxide dismutase (SOD) and levels of glutathione (GSH)
      and malondialdehyde (MDA) were examined in hippocampus of SCOP-treated mice. The
      cell death ratio was assessed by TUNEL staining, while apoptotic-related proteins
      including Bcl-2 and Bax were determined by immuno-fluorescent staining and
      western blot analysis. Caspase-3 was determined by western blot analysis.
      Consequently, a chromatographic condition, which was conducted at 35C with a flow
      rate of 0.8 ml/min on the Gemini C18 column with mobile phase of acetonitrile and
      water-phosphoric acid (100:0.1, v/v), was established to yield common fingerprint
      chromatography under 203 nm with a similarity index of 0.986 within 10 batches of
      BSYZ samples. BSYZ at a dose of 2.92 g/kg significantly improved the cognitive
      ability, restored the abnormal activity of SOD and increased the levels of MDA
      and GSH induced by SCOP. Moreover, the neural apoptosis in the hippocampus of
      SCOP-treated mice was reversed by BSYZ by regulating the expression of Bcl-2, Bax
      and caspase-3. The results demonstrated that BSYZ had neuroprotective effects in
      SCOP-induced senescence in mice by ameliorating oxidative stress and neuronal
      apoptosis in the brain, supporting its potential in AD treatment.

PMID- 24919923
TI  - The cascade of care in the Eastern European country of Georgia.
AB  - OBJECTIVES: Individual and public health benefits of antiretroviral therapy (ART)
      rely on successful engagement of HIV-infected patients in care. We aimed to
      evaluate the HIV care continuum in the Eastern European country of Georgia.
      METHODS: The analysis included all adult (age >= 18 years) HIV-infected patients
      diagnosed in Georgia from January 1989 until June 2012. Data were extracted from
      the national HIV/AIDS database as of 1 October 2012. The following stages of the
      HIV care continuum were quantified: HIV infected, HIV diagnosed, linked to care,
      retained in care, eligible for ART and virologically suppressed. RESULTS: Of 3295
      cumulative cases of adult HIV infection reported in Georgia, 2545 HIV-infected
      patients were known to be alive as of 1 October 2012, which is 52% of the
      estimated 4900 persons living with HIV in the country. Of the 2545 persons
      diagnosed with HIV infection, 2135 (84%) were linked to care and 1847 (73%) were
      retained in care. Of 1446 patients eligible for ART, 1273 (88%) were on treatment
      and 985 (77%) of them had a viral load <400 HIV-1 RNA copies/mL. Overall, 39% of
      those diagnosed and 20% of those infected had a suppressed viral load.
      CONCLUSIONS: The findings of our analysis demonstrate that the majority of
      patients diagnosed with HIV infection are retained in care. Loss of patients
      occurs at each step of the HIV care continuum, but the major gap is at the stage
      of HIV diagnosis. Reducing the number of persons living with undiagnosed HIV
      infection and simultaneously enhancing engagement in continuous care will be
      critical to achieve maximum individual and public health benefits of ART.

PMID- 24919924
TI  - Formulation of inhalable lipid-based salbutamol sulfate microparticles by spray
      drying technique.
AB  - BACKGROUND: The aim of this work was to develop dry powder inhaler (DPI)
      formulations of salbutamol sulfate (SS) by the aid of solid lipid microparticles
      (SLmPs), composed of biocompatible phospholipids or cholesterol. METHODS: The
      SLmPs were prepared by using two different solvent systems (ethanol and water
      ethanol) and lipid carriers (dipalmitoylphosphatidylcholine (DPPC) and
      cholesterol) with/without L-leucine in the spray drying process. The spray-dried
      microparticles were physically-mixed with coarse lactose monohydrate in order to
      make our final DPI formulations and were investigated in terms of physical
      characteristics as well as in vitro drug release profile and aerosolization
      behavior. RESULTS: We observed significant differences in the sizes,
      morphologies, and in vitro pulmonary depositions between the formulations. In
      particular, the SS-containing SLmPs prepared with water-ethanol (30:70 v/v)
      solution of DPPC and L-leucine which had then been blended with coarse lactose
      (1:9 w/w) exhibited the highest emitted dose (87.9%) and fine particle fraction
      (42.7%) among the formulations. In vitro drug release study indicated that
      despite of having a significant initial burst release for both cholesterol and
      DPPC-based microparticles, the remained drug released more slowly than the pure
      drug. CONCLUSION: This study demonstrated the potential of using lipid carriers
      as well as L-leucine in DPI formulations of SS to improve its aerosolization
      behavior and retard the release profile of the drug.

PMID- 24919925
TI  - Synthesis and biological evaluation of papain-family cathepsin L-like cysteine
      protease inhibitors containing a 1,4-benzodiazepine scaffold as antiprotozoal
      agents.
AB  - Novel papain-family cathepsin L-like cysteine protease inhibitors endowed with
      antitrypanosomal and antimalarial activity were developed, through an
      optimization study of previously developed inhibitors. In the present work, we
      studied the structure-activity relationships of these derivatives, with the aim
      to develop new analogues with a simplified and more synthetically accessible
      structure and with improved antiparasitic activity. The structure of the model
      compounds was significantly simplified by modifying or even eliminating the side
      chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a
      simple methylene spacer of appropriate length was inserted between the
      benzodiazepine ring and the 3-bromoisoxazoline moiety. Several rhodesain and
      falcipain-2 inhibitors displaying single-digit micromolar or sub-micromolar
      antiparasitic activity against one or both parasites were identified, with
      activities that were one order of magnitude more potent than the model compounds.

PMID- 24919926
TI  - The American Heart Association Life's Simple 7 and incident cognitive impairment:
      The REasons for Geographic And Racial Differences in Stroke (REGARDS) study.
AB  - BACKGROUND: Life's Simple 7 is a new metric based on modifiable health behaviors
      and factors that the American Heart Association uses to promote improvements to
      cardiovascular health (CVH). We hypothesized that better Life's Simple 7 scores
      are associated with lower incidence of cognitive impairment. METHODS AND RESULTS:
      For this prospective cohort study, we included REasons for Geographic And Racial
      Differences in Stroke (REGARDS) participants aged 45+ who had normal global
      cognitive status at baseline and no history of stroke (N=17 761). We calculated
      baseline Life's Simple 7 score (range, 0 to 14) based on smoking, diet, physical
      activity, body mass index, blood pressure, total cholesterol, and fasting
      glucose. We identified incident cognitive impairment using a 3-test measure of
      verbal learning, memory, and fluency obtained a mean of 4 years after baseline.
      Relative to the lowest tertile of Life's Simple 7 score (0 to 6 points), odds
      ratios of incident cognitive impairment were 0.65 (0.52, 0.81) in the middle
      tertile (7 to 8 points) and 0.63 (0.51, 0.79) in the highest tertile (9 to 14
      points). The association was similar in blacks and whites, as well as outside and
      within the Southeastern stroke belt region of the United States. CONCLUSIONS:
      Compared with low CVH, intermediate and high CVH were both associated with
      substantially lower incidence of cognitive impairment. We did not observe a dose
      response pattern; people with intermediate and high levels of CVH had similar
      incidence of cognitive impairment. This suggests that even when high CVH is not
      achieved, intermediate levels of CVH are preferable to low CVH.

PMID- 24919927
TI  - Increased intracortical inhibition in hyperglycemic hemichorea-hemiballism.
AB  - Hemichorea-hemiballism (HC-HB) in uncontrolled diabetes mellitus is an uncommon
      manifestation of hyperglycemia. The pathophysiology of hyperglycemic HC-HB is not
      well understood. A previous report showed increased intracortical inhibition in
      the motor cortex in a patient with diabetes with HC-HB. The objective of this
      study is to investigate motor cortex excitability in patients with hyperglycemic
      HC-HB. We hypothesized that intracortical inhibition measured with transcranial
      magnetic stimulation, which likely reflects the excitability of cortical gamma
      aminobutyric acid (GABA)ergic circuits, would be impaired in patients with
      hyperglycemic HC-HB. We studied 15 patients with mean age 71.5 years (range, 48
      94 y) and 12 age-matched healthy subjects. The motor cortex contralateral to the
      hemichorea was tested. Transcranial magnetic stimulation measures included motor
      evoked potential, recruitment curve, GABAA mediated short interval intracortical
      inhibition, intracortical facilitation, and GABAB mediated silent period duration
      and long interval intracortical inhibition. No significant difference was found
      in motor threshold, recruitment curve response, short interval intracortical
      inhibition, or intracortical facilitation in both rest and active conditions
      between patients with hyperglycemic HC-HB and normal subjects. However, long
      interval intracortical inhibition was significantly increased during muscle
      activation but not at rest in patients with hyperglycemic HC-HB. The silent
      period duration is also increased in patients with hyperglycemic HC-HB. We
      concluded that long interval intracortical inhibition and silent period are
      increased in the motor cortex contralateral to the hemichorea in hyperglycemic HC
      HB, but only during muscle activation. Hemichorea-hemiballism may be associated
      with increased GABAB receptor-mediated inhibitory activity in the motor cortex.

PMID- 24919928
TI  - The association of -330 interleukin-2 gene polymorphism and HLA-DR15 allele in
      Iranian patients with multiple sclerosis.
AB  - The purpose of this case-control study was to evaluate the frequencies and
      potential genetic susceptibility of the -330 IL2 T and G alleles and HLA
      DRB1*1501 allele in Iranian patients with multiple sclerosis (MS) compared to
      healthy controls. Two hundred and sixty Iranian patients with MS from medical
      genetics department of Sarem Women hospital were selected. Besides, 450
      ethnically age- and sex-matched healthy individuals without personal or family
      backgrounds of autoimmune disorders were enrolled as a control group. All
      polymorphisms were analysed using RFLP-PCR technique. HLA-DRB1 genotyping was
      carried out by HISTO TYPE SSP high-resolution Kits according to the
      manufacturer's suggestions. The frequency of the T allele at the -330 IL2
      polymorphism was significantly higher in patients with MS than controls (OR:
      2.45, 95 CI: 1.9-3, P = 4 * 10(-14) ). Moreover, the T/T genotype was more
      frequent in patients than in controls (51% vs. 30%). This study indicated that
      the -330 T IL2 allele and the T/T genotype were related to increased plasma
      concentration of IL2 and a higher risk of developing MS among Iranian patients.
      Carrying both the -330 T IL2 and the HLA, DRB1* 1501 alleles showed the most
      susceptibly effect to MS. Our data demonstrated -330 T IL2 allele provided major
      susceptibility to MS and HLA-DRB1* 1501 allele had an additive effect. In
      addition, it seems that studies with larger sample size are required to bring
      about more authentic results. Our findings suggest that IL2 gene polymorphisms
      influence the susceptibility to MS in Iranian patients.

PMID- 24919929
TI  - Cisplatin-induced testicular dysfunction and its amelioration by Launaea
      taraxacifolia leaf extract.
AB  - This study investigates the ameliorative potential of Launea taraxacifolia (LT)
      aqueous leaf extract on cisplatin-induced testicular dysfunction in Wistar rats.
      Thirty rats were randomly divided into six groups (A-F) of 5 rats each: Group A
      which served as control received water; Group B was intraperitoneally (ip)
      injected 10 mg kg(-1) body wt cisplatin on day 21; Groups C and D were given 100
      and 400 mg of LT via oral administration, respectively, for 21 days while Groups
      E and F received similar treatment as Groups C and D, respectively, and then
      exposed to ip administration of 10 mg kg(-1) body weight cisplatin on the 21st
      day. Exclusively, Cisplatin-exposed Group B rats showed reduced sperm
      characteristics and increased sperm morphological abnormalities; distorted
      histological architecture of seminiferous tubules; significantly increased lipid
      peroxidation (LPO) and decreased activities of superoxide dismutase (SOD),
      catalase (CAT) and glutathione (GSH)levels in the testes. These parameters in LT
      alone treated Groups C and D were not markedly different compared with the
      control group. The rats with the combined treatment in Groups E and F showed
      significantly improved sperm parameters, testicular histo-architecture and
      antioxidant enzymatic activities. Conclusively, aqueous extract of L.
      taraxacifolia has protective potential against cisplatin damage. 

PMID- 24919930
TI  - Scale of health: indices of safety and efficacy in the evolving environment of
      large biological datasets.
AB  - The interdependent relationship between pharmacology and toxicology is
      fundamental to the concepts of efficacy and safety of both drugs and xenobiotics.
      The traditional concept of establishing efficacious and tolerated doses to define
      a 'therapeutic window' appears simplistic in the context of an exponentially
      increasing database on molecular mechanisms and cell biology that inform our
      understanding of homeostasis. Recent advances in nano medicine illustrate the
      convergence of efficacy and safety considerations that are central to
      establishing a clear pathway for regulatory review. The following overview
      considers biological responses to the administration of nanoparticles and the
      scale of balanced, within a range that might be considered 'normal', to
      unbalanced, abnormal responses associated with health and disease. 

PMID- 24919931
TI  - Characterization of endogenous G-CSF and the inverse correlation to chemotherapy
      induced neutropenia in patients with breast cancer using population modeling.
AB  - PURPOSE: Neutropenia is a severe adverse-event of chemotherapeutics. Neutrophils
      (ANC) are mainly regulated by granulocyte colony stimulating factor (G-CSF). The
      aim was to characterize the dynamics between endogenous G-CSF and ANC over time
      following chemotherapy. METHODS: Endogenous G-CSF and ANC were monitored in forty
      nine breast cancer patients treated with sequential adjuvant 5-fluorouracil
      epirubicin-cyclophosphamide and docetaxel. RESULTS: During treatment courses ANC
      was transiently decreased and was reflected in an endogenous G-CSF increase,
      which was well described by a semi-mechanistic model including control
      mechanisms; when G-CSF concentrations increased the proliferation rate increased
      and the bone maturation time reduced for ANC. Subsequently, ANC in the
      circulation increased leading to increased elimination of G-CSF. Additionally, a
      non-specific elimination for G-CSF was quantified. The ANC-dependent elimination
      contributed to 97% at baseline and 49% at an ANC of 0.1 . 10(9)/L to the total G
      CSF elimination. CONCLUSION: The integrated G-CSF-myelosuppression model captured
      the initial rise in endogenous G-CSF following chemotherapy-induced neutropenia
      and the return to baseline of G-CSF and ANC. The model supported the self
      regulatory properties of the system and may be a useful tool for further
      characterization of the biological system and in optimization of chemotherapy
      treatment.

PMID- 24919933
TI  - Health and social outcomes for transitioning youth.

PMID- 24919932
TI  - Tumor-targeted responsive nanoparticle-based systems for magnetic resonance
      imaging and therapy.
AB  - PURPOSE: Design and synthesis of a tumor responsive nanoparticle-based system for
      imaging and treatment of various cancers. METHODS: Manganese oxide nanoparticles
      (Mn3O4 NPs) were synthesized and modified with LHRH targeting peptide or anti
      melanoma antibodies (cancer targeting moieties) and a MMP2 cleavable peptide (a
      possible chemotactic factor). Nanostructured lipid carriers (NLCs) were used to
      entrap the BRAF inhibitor, vemurafenib, and enhance cytotoxicity of the drug.
      Size distribution, stability, drug entrapment, cytotoxicity and genotoxicity of
      synthesized nanoparticles were studied in vitro. Enhancement of MRI signal by
      nanoparticles and their body distribution were examined in vivo on mouse models
      of melanoma, ovarian and lung cancers. RESULTS: Uniform, stable cancer-targeted
      nanoparticles (PEGylated water-soluble Mn3O4 NPs and NLCs) were synthesized. No
      signs of cyto-,genotoxicity and DNA damage were detected for nanoparticles that
      do not contain an anticancer drug. Entrapment of vemurafenib into nanoparticles
      significantly enhanced drug toxicity in cancer cells with targeted V600E
      mutation. The developed nanoparticles containing LHRH and MMP2 peptides showed
      preferential accumulation in primary and metastatic tumors increasing the MRI
      signal in mice with melanoma, lung and ovarian cancers. CONCLUSIONS: The proposed
      nanoparticle-based systems provide the foundation for building an integrated MRI
      diagnostic and therapeutic approach for various types of cancer.

PMID- 24919934
TI  - The health care transition research consortium health care transition model: a
      framework for research and practice.
AB  - The body of health care transition (HCT) research is in the early stages of
      development. One of the major limitations of this developing field of research is
      the lack of theoretically-directed studies. This research limitation has hindered
      understanding of the variables contributing to successful HCT. The inadequate
      understanding of HCT is due largely to the absence of an adequate conceptual
      model that addresses the complexity and the relationships amongst variables that
      influence HCT outcomes among adolescents and emerging adults with special health
      care needs (AEA-SHCN). Existing conceptual models do not sufficiently address the
      significant interrelationships amongst variables to explain, predict and/or
      control AEA-SHCN's biopsychosocial HCT outcomes. This article provides a
      description of a health care transition theoretical model developed by the
      international and interdisciplinary Health Care Transition Research Consortium
      (HCTRC) that can be applied for testing in research and serve as a framework for
      clinical practice and policymaking. The HCTRC model is composed of four domains
      that are considered integral to the HCT phenomenon: Individual, Family/Social
      Support, Environment, and the Health Care System. The HCTRC model specifies the
      variables, processes, and potential mediators and moderators that affect the HCT
      outcomes. 

PMID- 24919935
TI  - Opportunities lost and found: experiences of patients with cerebral palsy and
      their parents transitioning from pediatric to adult healthcare.
AB  - PURPOSE: To describe and define the experiences of adults with cerebral palsy
      (CP) and parents of adults with CP who have been involved in a transfer of
      physiatry care from pediatric to adult healthcare and to explore their
      experiences more generally in the transition from pediatric to adult services.
      METHODS: A qualitative research approach was used. Semi-structured focus group
      interviews were conducted with adults with CP (n=5) and parents of adults with CP
      (n=8) to explore the health care transition (HCT) process from pediatric to adult
      healthcare. Four key content domains were used to facilitate the focus groups; 1)
      Transition Planning, 2) Accessibility of Services, 3) Experience with Adult
      Providers, and 4) Recommendations for Improving the Transition Process.
      Conventional content analysis was used to analyze the data. RESULTS: Four themes
      emerged from the focus groups; Lost in Transition, Roadmap to Care, List of None,
      and One Stop Shopping. Participants felt lost in the HCT process, requested a
      transparent transition plan, expressed concern regarding access to adult
      healthcare, and made recommendations for improvements. CONCLUSION: Challenges in
      transitioning from pediatric to adult health care were identified by all
      participants and several strategies were recommended for improvement.

PMID- 24919936
TI  - The road to independence: lived experiences of youth with chronic conditions and
      their parents compared.
AB  - PURPOSE: To gain insight into the development of young persons with chronic
      conditions towards independence by comparing their lived experiences to those of
      their parents. METHODS: Semi-structured interviews were held with 16 young
      persons (7 males, 9 females; 15-22 years) and one of their parents (n=16), asking
      about the young persons' daily lives and their development towards adulthood.
      Themes were deductively derived from the Skills for Growing Up framework, i.e.
      agency, living and daily activities, social and intimate relationships,
      education, work, leisure activities, transportation, and healthcare. Parents also
      reflected on how they dealt with the child's chronic condition. A paired thematic
      analysis was conducted. RESULTS: Parents were often less convinced that their
      children could act independently than the young persons themselves. They were
      concerned about them and tended to interfere with their daily lives, often to the
      annoyance of their children. Also, parents often perceived more barriers in
      social participation, while young persons were more positive. CONCLUSION: The
      perceptions of young persons and their parents clashed on living independently,
      intimate relationships, leisure activities, and healthcare. Young people might
      benefit from professional support in these domains to help them strengthen their
      autonomy and to prevent child-parent conflict and negative outcomes.

PMID- 24919938
TI  - Follow-up of individuals with cerebral palsy through the transition years and
      description of adult life: the Swedish experience.
AB  - OBJECTIVE: To describe the process of providing healthcare through the transition
      years to individuals with cerebral palsy (CP) and to present data on living
      arrangements, education/occupation status, and use of personal assistance in
      young Swedish adults with CP. METHODS: A descriptive cross-sectional study of 102
      participants (63 males) participating in a standardized follow-up program called
      CPUP. Data were analyzed in relation to the Gross Motor Function Classification
      System (GMFCS) and the Manual Ability Classification System (MACS). RESULTS: Of
      the participants, 58 "lived with parents", 29 reported "independent living", and
      15 reported "special service housing". Living arrangements differed among GMFCS
      levels (p< 0.001) and 14 of 20 with severe disabilities lived with their parents.
      Thirty-four of 70 reported personal assistance; use of assistance correlated (p<
      0.001) with GMFCS (r(s) =0.71) and MACS (r(s) = 0.70). Thirty five were
      "students", 20 "employed", 36 in "daily activities", and 9 were "unemployed". Of
      those employed, 18 had GMFCS levels I-II. CONCLUSION: Some young adults with CP
      and severe functional limitations manage independent living - however, many still
      live with their parents. Although many are students, a large number are
      unemployed. There is disconnect between the pediatric and adult healthcare
      systems. CPUP may facilitate in making the transition smoother.

PMID- 24919937
TI  - Transition and transfer of adolescents and young adults with pediatric onset
      chronic disease: the patient and parent perspective.
AB  - PURPOSE: To determine patients' and parents' perceptions regarding the delivery
      of transition education and perceived barriers to transfer to adult oriented
      care. METHODS: A self-report survey was administered to a convenience sample of
      patients (16-25 years old) with various childhood onset chronic diseases. A
      similar survey was administered to their parents/guardians. RESULTS: A total of
      155 patients and 104 parents participated in the study. The mean age of patients
      was 18.8 +/- 2.3 years; 57% were female. Although most patients and parents
      reported receiving information and training about their medical condition,
      significant gaps in other aspects of transition education were identified. These
      included stated deficiencies in education regarding unprotected intercourse,
      health of future offspring, birth control, pregnancy, illicit drug use, and
      future career or vocation counseling. Commonly cited barriers to transfer were
      emotional attachments and lack of adult medicine specialty providers; however,
      the majority anticipated being ready to transfer to adult oriented care by age 25
      years. CONCLUSION: There are significant gaps in the delivery of transition
      education as perceived by patients and their parents. Standardization of
      transition education may help ensure that patients acquire the knowledge and
      skills for health care self-management in adulthood and successful transfer to
      adult oriented care.

PMID- 24919939
TI  - Transition of adolescents with chronic health conditions to adult primary care:
      factors associated with physician acceptance.
AB  - PURPOSE: To assess the willingness of adult primary-care physicians to transfer
      young adults with special health care needs (YASHCN) into their practices, and
      the relative impact of patient characteristics and transition supports. METHODS:
      Survey of primary care internists and family practitioners using randomized
      patient characteristics and transition supports in clinical vignettes to assess
      physician willingness to accept a YASHCN into their practice. RESULTS: 404
      responses were received from 601 surveys (response rate 67%). Only 44% rated
      themselves "willing" or "enthusiastic" to accept a YASHCN. Using four-way ANOVA
      testing, provider and practice characteristics significantly associated with
      willingness to accept included gender, years in practice, presence of YASHCN in
      current practice and whether the practice was accepting new patients. Patient
      condition and transition support significantly affected willingness to accept;
      training in internal medicine versus family practice did not. CONCLUSION:
      Physicians providing primary care for adults express limited willingness to
      accept YASHCN into their practices. Provider, practice and patient
      characteristics affected willingness to accept. Although transition supports
      affected willingness to accept, effects varied markedly across diagnoses and
      physician gender. Findings have implications for patients and healthcare teams
      and policy planners.

PMID- 24919940
TI  - Federal and state benefits for transition age youth.
AB  - While all children face challenges as they become adults, children with chronic
      medical conditions or disabilities face unique barriers in their transition to
      adulthood. Children, especially those who are low income and have special needs,
      are eligible for a range of supports including income supports, health care
      coverage, vocational and educational supports. These supports are critical to
      sound health because they ensure access to necessary medical services, while also
      offsetting the social determinants that negatively affect health. Unfortunately,
      as children transition into adulthood, eligibility for these benefits can change
      abruptly or even end entirely. If medical providers have a better understanding
      of five transition key dates, they can positively impact their patients' health
      by ensuring continuous coverage through the transition to adulthood. The key
      dates are as follows: (1) transition services for students with an Individualized
      Education Program (IEP) must begin by age 16 (in some states such as Illinois,
      these services must be in place by age 14 1/2); (2) at age 18, eligibility for
      income supports may change; (3) at age 19, eligibility for Medicaid may change;
      (4) at graduation, eligibility for educational supports will end unless steps are
      taken to extend those benefits until age 22; and (5) when individuals prepare to
      enter the workforce, they will become eligible for vocational rehabilitation
      services. With an understanding of these key transition dates and how to partner
      with social services and advocacy organizations on behalf of their patients,
      medical providers can help to ensure that transition-age patients retain the
      holistic social services and supports they need to protect their health. 

PMID- 24919941
TI  - The LIFEspan model of transitional rehabilitative care for youth with
      disabilities: healthcare professionals' perspectives on service delivery.
AB  - PURPOSE: LIFEspan is a service delivery model of continuous coordinated care
      developed and implemented by a cross-organization partnership between a pediatric
      and an adult rehabilitation hospital. Previous work explored enablers and
      barriers to establishing the partnership service. This paper examines healthcare
      professionals' (HCPs') experiences of 'real world' service delivery aimed at
      supporting transitional rehabilitative care for youth with disabilities. METHODS:
      This qualitative study - part of an ongoing mixed method longitudinal study -
      elicited HCPs' perspectives on their experiences of LIFEspan service delivery
      through in-depth interviews. Data were categorized into themes of service
      delivery activities, then interpreted from the lens of a service
      integration/coordination framework. RESULTS: Five main service delivery themes
      were identified: 1) addressing youth's transition readiness and capacities; 2)
      shifting responsibility for healthcare management from parents to youth; 3)
      determining services based on organizational resources; 4) linking between
      pediatric and adult rehabilitation services; and, 5) linking with multi-sector
      services. CONCLUSIONS: LIFEspan contributed to service delivery activities that
      coordinated care for youth and families and integrated inter-hospital services.
      However, gaps in service integration with primary care, education, social, and
      community services limited coordinated care to the rehabilitation sector.
      Recommendations are made to enhance service delivery using a systems/sector-based
      approach.

PMID- 24919942
TI  - Implementation and sustainability of statewide transition support services for
      youth with intellectual and physical disabilities.
AB  - PURPOSE: Significant gaps in care and limited existing models establish the need
      to innovate systems of care for youth with special health care needs in the
      transition between pediatric to adult health care settings. METHODS: Using
      implementation science, a statewide transition support program was created.
      University and community partners explored needs and adopted a strategic plan and
      funding sources. The existing consensus statement provided a framework. A team
      was hired, policies were piloted and the initial ambulatory consultative
      transition service for youth with special needs ages 11 to 22 was launched. Full
      program activities during year four were analyzed. RESULTS: During 2011, there
      were 139 consultations for youth with intellectual disability and/or physical
      disability (average 16.74 years, 46% female). Services include routine and
      focused co-morbidity screening and recommendations, care coordination of complex
      health and community service needs, and support for families. The evolving
      transdisciplinary team adapted their methods to collaborate with a growing
      population of youth and primary care providers. CONCLUSION: A statewide
      transition support program is a viable delivery model to provide needed resources
      for youth, families and primary care practices. Weekly improvement meetings
      continue to adapt services to sustain family satisfaction and community provider
      satisfaction.

PMID- 24919944
TI  - Altered right ventricular contractile pattern after cardiac surgery: monitoring
      of septal function is essential.
AB  - Assessment of right ventricular (RV) function is important in the management of
      various forms of cardiovascular disease. Accurately assessing RV volume and
      systolic function is a challenge in day-to-day clinical practice due to its
      complex geometry. Tricuspid annular plane systolic excursion (TAPSE) and systolic
      excursion velocity (S') have been reviewed to further assess their suitability
      and objectivity in evaluating RV function. Multiple studies have validated their
      diagnostic and prognostic values in numerous pathologic conditions. Diminished
      longitudinal contraction after cardiothoracic surgery is a well-known phenomenon,
      but it is not well validated. Despite significant reduction in RV performance
      along the long-axis assessed by TAPSE and S' after cardiac surgery, RV ejection
      fractions did not change as well as the left ventricular parameters and exercise
      capacity. RV contractile patterns were markedly altered with decreased
      longitudinal shortening and increased transverse shortening, which are likely
      resulted from the septal damage during cardiac surgery. The septum is essential
      for RV performance due to its oblique fiber orientation. This allows ventricular
      twisting, which is a vital mechanism against increased pulmonary vascular
      resistance. The septum function along with TAPSE and S' should be adequately
      assessed during cardiac surgery, and evidence of septal dysfunction should lead
      to reevaluation of myocardial protection methods. 

PMID- 24919945
TI  - A novel multifunctional NiTi/Ag hierarchical composite.
AB  - Creating multifunctional materials is an eternal goal of mankind. As the
      properties of monolithic materials are necessary limited, one route to extending
      them is to create a composite by combining contrasting materials. The potential
      of this approach is neatly illustrated by the formation of nature materials where
      contrasting components are combined in sophisticated hierarchical designs. In
      this study, inspired by the hierarchical structure of the tendon, we fabricated a
      novel composite by subtly combining two contrasting components: NiTi shape-memory
      alloy and Ag. The composite exhibits simultaneously exceptional mechanical
      properties of high strength, good superelasticity and high mechanical damping,
      and remarkable functional properties of high electric conductivity, high
      visibility under fluoroscopy and excellent thermal-driven ability. All of these
      result from the effective-synergy between the NiTi and Ag components, and place
      the composite in a unique position in the properties chart of all known
      structural-functional materials providing new opportunities for innovative
      electrical, mechanical and biomedical applications. Furthermore, this work may
      open new avenues for designing and fabricating advanced multifunctional materials
      by subtly combining contrasting multi-components. 

PMID- 24919946
TI  - A quantitative perspective on ethics in large team science.
AB  - The gradual crowding out of singleton and small team science by large team
      endeavors is challenging key features of research culture. It is therefore
      important for the future of scientific practice to reflect upon the individual
      scientist's ethical responsibilities within teams. To facilitate this reflection
      we show labor force trends in the US revealing a skewed growth in academic ranks
      and increased levels of competition for promotion within the system; we analyze
      teaming trends across disciplines and national borders demonstrating why it is
      becoming difficult to distribute credit and to avoid conflicts of interest; and
      we use more than a century of Nobel prize data to show how science is outgrowing
      its old institutions of singleton awards. Of particular concern within the large
      team environment is the weakening of the mentor-mentee relation, which undermines
      the cultivation of virtue ethics across scientific generations. These trends and
      emerging organizational complexities call for a universal set of behavioral norms
      that transcend team heterogeneity and hierarchy. To this end, our expository
      analysis provides a survey of ethical issues in team settings to inform science
      ethics education and science policy. 

PMID- 24919947
TI  - Pretreatment with andrographolide pills((r)) attenuates lipopolysaccharide
      induced pulmonary microcirculatory disturbance and acute lung injury in rats.
AB  - OBJECTIVE: The purpose of this study was to explore the protective effect of AP
      on LPS-induced PMD and ALI. METHODS: Male SD rats were continuously infused with
      LPS (5 mg/kg/h) for one hour to induce PMD and ALI. AP was administrated orally
      one hour before LPS exposure. Arterial blood pressure and HR were monitored.
      Blood gas analysis, histological observation, cytokines in plasma, leukocyte
      recruitment, pulmonary oxidative stress, microvessel permeability, edema, and
      related proteins were evaluated six hours after LPS challenge. RESULTS: Rats
      receiving LPS exhibited significant alterations, including hypotension,
      tachycardia, increase in cytokines, neutrophil adhesion and infiltration,
      oxidative stress, and microvessel hyperpermeability, resulting in pulmonary
      injury and dysfunction. AP (0.18 g/kg or 1.8 g/kg) improved rat survival rate,
      and significantly attenuated all aforementioned insults, and inhibited LPS
      induced increase in adhesion molecules, up-regulation of Cav-1 and Src kinase and
      NADPH oxidase subunits (p47(phox) and p67(phox) ) membrane translocation in lung
      tissue, and preserved JAM-1 and claudin-5. CONCLUSIONS: The results demonstrated
      the protective effect of AP on LPS-induced PMD and ALI, suggesting the potential
      of AP as a prophylactic strategy for LPS-induced ALI.

PMID- 24919948
TI  - Event- and interval-based measurement of stuttering: a review.
AB  - BACKGROUND: Event- and interval-based measurements are two different ways of
      computing frequency of stuttering. Interval-based methodology emerged as an
      alternative measure to overcome problems associated with reproducibility in the
      event-based methodology. No review has been made to study the effect of
      methodological factors in interval-based absolute reliability data or to compute
      the agreement between the two methodologies in terms of inter-judge, intra-judge
      and accuracy (i.e., correspondence between raters' scores and an established
      criterion). AIMS: To provide a review related to reproducibility of event-based
      and time-interval measurement, and to verify the effect of methodological factors
      (training, experience, interval duration, sample presentation order and judgment
      conditions) on agreement of time-interval measurement; in addition, to determine
      if it is possible to quantify the agreement between the two methodologies METHODS
      & PROCEDURES: The first two authors searched for articles on ERIC, MEDLINE,
      PubMed, B-on, CENTRAL and Dissertation Abstracts during January-February 2013 and
      retrieved 495 articles. Forty-eight articles were selected for review. Content
      tables were constructed with the main findings. MAIN CONTRIBUTION: Articles
      related to event-based measurements revealed values of inter- and intra-judge
      greater than 0.70 and agreement percentages beyond 80%. The articles related to
      time-interval measures revealed that, in general, judges with more experience
      with stuttering presented significantly higher levels of intra- and inter-judge
      agreement. Inter- and intra-judge values were beyond the references for high
      reproducibility values for both methodologies. Accuracy (regarding the closeness
      of raters' judgements with an established criterion), intra- and inter-judge
      agreement were higher for trained groups when compared with non-trained groups.
      Sample presentation order and audio/video conditions did not result in
      differences in inter- or intra-judge results. A duration of 5 s for an interval
      appears to be an acceptable agreement. Explanation for high reproducibility
      values as well as parameter choice to report those data are discussed.
      CONCLUSIONS & IMPLICATIONS: Both interval- and event-based methodologies used
      trained or experienced judges for inter- and intra-judge determination and data
      were beyond the references for good reproducibility values. Inter- and intra
      judge values were reported in different metric scales among event- and interval
      based methods studies, making it unfeasible to quantify the agreement between the
      two methods.

PMID- 24919949
TI  - Feeding ecology and trophic comparisons of six shark species in a coastal
      ecosystem off southern Brazil.
AB  - The diets of six shark species, Sphyrna lewini, Sphyrna zygaena, Carcharhinus
      obscurus, Carcharhinus limbatus, Rhizoprionodon lalandii and Galeocerdo cuvier,
      were investigated in a subtropical coastal ecosystem of southern Brazil. Stomach
      content data were obtained to assess foraging niche segregation and ontogenetic
      shifts in the diets of these sharks. Five of the shark species off the Parana
      coast were ichthyophagous, with the exception of S. zygaena, which was
      teutophagous. With the exception of G. cuvier, which had a generalist diet, the
      other five species displayed specialization in their feeding. Ontogenetic shifts
      were observed in C. obscurus and S. lewini with large individuals consuming
      elasmobranchs. Owing to the diet overlap between C. obscurus and S. lewini, C.
      obscurus and C. limbatus and R. lalandii and C. limbatus, future studies on the
      spatial and temporal distributions of these species are needed to understand the
      extent of competitive interactions. 

PMID- 24919950
TI  - Predictive power of UKCAT and other pre-admission measures for performance in a
      medical school in Glasgow: a cohort study.
AB  - BACKGROUND: The UK Clinical Aptitude Test (UKCAT) and its four subtests are
      currently used by 24 Medical and Dental Schools in the UK for admissions. This
      longitudinal study examines the predictive validity of UKCAT for final
      performance in the undergraduate medical degree programme at one Medical School
      and compares this with the predictive validity of the selection measures
      available pre-UKCAT. METHODS: This was a retrospective observational study of one
      cohort of students, admitted to Glasgow Medical School in 2007. We examined the
      associations which UKCAT scores, school science grades and pre-admissions
      interview scores had with performance indicators, particularly final composite
      scores that determine students' postgraduate training opportunities and overall
      ranking (Educational Performance Measure - EPM, and Honours and Commendation -
      H&C). Analyses were conducted both with and without adjustment for potential
      socio-demographic confounders (gender, age, ethnicity and area deprivation).
      RESULTS: Despite its predictive value declining as students progress through the
      course, UKCAT was associated with the final composite scores. In mutually
      adjusted analyses (also adjusted for socio-demographic confounders), only UKCAT
      total showed independent relationships with both EPM (p = 0.005) and H&C (p =
      0.004), school science achievements predicted EPM (p = 0.009), and pre-admissions
      interview score predicted neither. UKCAT showed less socio-demographic variation
      than did TSS. CONCLUSION: UKCAT has a modest predictive power for overall course
      performance at the University of Glasgow Medical School over and above that of
      school science achievements or pre-admission interview score and we conclude that
      UKCAT is the most useful predictor of final ranking.

PMID- 24919952
TI  - Influence of juniper (Juniperus communis) oil on growth performance and meat
      quality as a natural antioxidant in quail diets.
AB  - 1. This study aimed to evaluate the effects of juniper oil on growth performance
      and meat quality in quails to determine its use as a safe and natural method to
      reduce overdependence on the use of antibiotic. 2. A total of 1000 1-d-old
      Pharaoh (Coturnix coturnix Pharaoh) quails, including both males and females,
      were divided into 4 groups containing 250 quails and treated as follows: (1) a
      control group with 0 mg volatile oil/kg diet; (2) 100 mg/kg juniper oil; (3) 150
      mg/kg juniper oil and (4) 200 mg/kg juniper oil. The diets were prepared fresh
      for each treatment. The experiment was carried out for 42 d. 3. The results of
      the study showed that supplementation with juniper oil (100 and 150 mg/kg) caused
      a significant increase in live weight, live weight gain and carcass yields during
      the growing and finishing periods. Feed intake and feed conversion ratio were not
      significantly influenced by treatments. 4. The quails given rations containing
      juniper oil had reduced thiobarbituric acid levels in raw thigh meat samples at
      different storage times. Juniper oil was found to have significant antioxidant
      activity and prevented lipid oxidation in stored meat. 5. In conclusion, natural
      antioxidants such as a juniper oil can be used instead of synthetic antioxidants
      to retard lipid oxidation in animal diets to improve meat product quality and
      animal performance.

PMID- 24919951
TI  - Nicastrin and Notch4 drive endocrine therapy resistance and epithelial to
      mesenchymal transition in MCF7 breast cancer cells.
AB  - INTRODUCTION: Resistance to anti-estrogen therapies is a major cause of disease
      relapse and mortality in estrogen receptor alpha (ERalpha)-positive breast
      cancers. Tamoxifen or estrogen withdrawal increases the dependence of breast
      cancer cells on Notch signalling. Here, we investigated the contribution of
      Nicastrin and Notch signalling in endocrine-resistant breast cancer cells.
      METHODS: We used two models of endocrine therapies resistant (ETR) breast cancer:
      tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF7 cells. We
      evaluated the migratory and invasive capacity of these cells by Transwell assays.
      Expression of epithelial to mesenchymal transition (EMT) regulators as well as
      Notch receptors and targets were evaluated by real-time PCR and western blot
      analysis. Moreover, we tested in vitro anti-Nicastrin monoclonal antibodies
      (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal
      therapeutic agents. Finally, we generated stable Nicastrin overexpessing MCF7
      cells and evaluated their EMT features and response to tamoxifen. RESULTS: We
      found that ETR cells acquired an epithelial to mesenchymal transition (EMT)
      phenotype and displayed increased levels of Nicastrin and Notch targets.
      Interestingly, we detected higher level of Notch4 but lower levels of Notch1 and
      Notch2 suggesting a switch to signalling through different Notch receptors after
      acquisition of resistance. Anti-Nicastrin monoclonal antibodies and the GSI
      PF03084014 were effective in blocking the Nicastrin/Notch4 axis and partially
      inhibiting the EMT process. As a result of this, cell migration and invasion were
      attenuated and the stem cell-like population was significantly reduced. Genetic
      silencing of Nicastrin and Notch4 led to equivalent effects. Finally, stable
      overexpression of Nicastrin was sufficient to make MCF7 unresponsive to tamoxifen
      by Notch4 activation. CONCLUSIONS: ETR cells express high levels of Nicastrin and
      Notch4, whose activation ultimately drives invasive behaviour. Anti-Nicastrin
      mAbs and GSI PF03084014 attenuate expression of EMT molecules reducing cellular
      invasiveness. Nicastrin overexpression per se induces tamoxifen resistance linked
      to acquisition of EMT phenotype. Our finding suggest that targeting Nicastrin
      and/or Notch4 warrants further clinical evaluation as valid therapeutic
      strategies in endocrine-resistant breast cancer.

PMID- 24919953
TI  - Post-exposure rate of tuberculosis infection among health care workers measured
      with tuberculin skin test conversion after unprotected exposure to patients with
      pulmonary tuberculosis: 6-year experience in an Italian teaching hospital.
AB  - BACKGROUND: This study assesses the risk of LTBI at our Hospital among HCWs who
      have been exposed to TB patients with a delayed diagnosis and respiratory
      protection measures were not implemented. METHODS: All HCWs exposed to a patient
      with cultural confirmed pulmonary TB and respiratory protection measures were not
      implemented were included. Data on TST results performed in the past (defined as
      T0) were recorded. TST was performed twice: first, immediately after exposure to
      an index patient (T1) and three months later (T2). The period of time between T0
      and T1 was used to calculate he annual rate of tuberculosis infection (ARTI),
      while le period of time between T1 and T2 was used to calculate the post exposure
      annual rate of tuberculosis infection (PEARTI). RESULTS: Fourteen index patients
      were admitted; sputum smear was positive in 7 (58.3%), 4 (28.6%) were non-Italian
      born patients. 388 HCWs were exposed to index patients, a median of 27 (12-39)
      HCW per each index patient. One hundred eighty (46.4%) HCWs received BCG in the
      past. One hundred twenty two HCWs (31%) were TST positive at a previous routine
      screening and not evaluated in this subset. Among the remaining 255 HCWs with
      negative TST test in the past, TST at T1 was positive in 11 (4.3%). ARTI was 1.6
      (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, that were
      TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100 PY. At univariate
      analysis, older age was associated with post exposure latent tuberculosis
      infection (HR 1.12; 95% CI 1.03-1.22, p=0.01). CONCLUSIONS: PEARTI was
      considerably higher among HCWs exposed to index patients than ARTI. These data
      underscore the overwhelming importance of performing a rapid diagnosis, as well
      as implementing adequate respiratory protection measures when TB is suspected.

PMID- 24919954
TI  - Comparative study of NMP-preloaded and dip-loaded membranes for guided bone
      regeneration of rabbit cranial defects.
AB  - Guided bone regeneration (GBR) has been utilized for several decades for the
      healing of cranio-maxillofacial bone defects and, particularly in the dental
      field, by creating space with a barrier membrane to exclude soft tissue and
      encourage bone growth in the membrane-protected volume. Although the first
      membranes were non-resorbable, a new generation of GBR membranes aims to
      biodegrade and provide bioactivity for better overall results. The Inion GTRTM
      poly(lactide-co-glycolide) (PLGA) membrane is not only resorbable but also
      bioactive, since it includes N-methylpyrrolidone (NMP), which has been shown to
      promote bone regeneration. In this study, the effects of loading different
      amounts of NMP onto the membrane through chemical vapour deposition or dipping
      have been explored. In vitro release demonstrated that lower levels of NMP led to
      lower NMP concentrations and slower release, based on total NMP loaded in the
      membrane. The dipped membrane released almost all of the NMP within 15 min,
      leading to a high NMP concentration. For the in vivo studies in rabbits, 6 mm
      calvarial defects were created and left untreated or covered with an ePTFE
      membrane or PLGA membranes dipped in, or preloaded with, NMP. Evaluation of the
      bony regeneration revealed that the barrier membranes improved bony healing and
      that a decrease in NMP content improved the performance. Overall, we have
      demonstrated the potential of these PLGA membranes with a more favourable NMP
      release profile and the significance of exploring the effect of NMP on these PLGA
      membranes with regard to bone ingrowth. Copyright (c) 2014 John Wiley & Sons,
      Ltd.

PMID- 24919955
TI  - Elevated expression of AKT2 correlates with disease severity and poor prognosis
      in human osteosarcoma.
AB  - Members of AKT kinase family are central modulators in numerous signaling
      cascades, which regulate metabolism, cell proliferation, survival and growth.
      Previously, the knockdown of AKT2 expression has been demonstrated to enhance the
      efficacy of chemotherapy in patients with osteosarcoma. However, it is currently
      unknown whether the aberrant expression of AKT2 has relevance to the progression
      of osteosarcoma. The aim of the present study was to investigate the
      clinicopathological and prognostic value of AKT2 in osteosarcoma. Formalin-fixed
      paraffin embedded osteosarcoma and self-paired non-cancerous bone tissue samples
      were obtained from 126 patients with osteosarcomas. AKT2 expression was detected
      by an immunohistochemistry assay. Patient survival rates were determined by the
      Kaplan-Meier method and log-rank test. Cox regression was adopted for
      multivariate analysis of the prognostic factors to examine the effect of AKT on
      event-free survival and overall survival in patients with osteosarcomas. AKT2
      expression in osteosarcoma tissues was significantly higher than that in non
      cancerous bone tissues (immunostaining score, 6.39+/-1.62 vs. 3.46+/-1.03;
      P<0.001). In addition, the elevated expression of AKT2 protein was significantly
      associated with positive recurrence (P=0.023), the presence of metastasis
      (P=0.006) and poor response to chemotherapy (P=0.015). Furthermore, patients with
      high AKT2 expression had significantly shorter event-free survival (P<0.001) and
      overall survival times (P<0.001) than those with lower expression levels.
      Multivariate analysis further demonstrated that AKT2 expression (P=0.029 and
      0.016, respectively), the status of recurrence (P=0.018 and 0.012, respectively)
      and metastasis (P=0.020 and 0.015, respectively), and the response to
      chemotherapy (P=0.011 and 0.008, respectively) were all independent prognostic
      factors for event-free survival and overall survival time. To the best of our
      knowledge, these data have supported the findings for the first time, that the
      elevated expression of AKT2 may be associated with aggressive clinical behavior
      and poor outcome in patients with osteosarcomas. Therefore, AKT2 may be a
      candidate marker of unfavorable prognosis in osteosarcoma. 

PMID- 24919956
TI  - One-pot synthesis of benzo[4,5]imidazo[1,2-a]quinazoline derivatives via facile
      transition-metal-free tandem process.
AB  - A one-pot transition metal-free method for synthesizing benzo[4,5]imidazo[1,2
      a]quinazoline and imidazo[1,2-a]quinazoline derivatives has been developed. The
      approach is widely applicable to 2-fluoro-, 2-chloro-, 2-bromo- and 2-nitro
      substituted aryl aldehyde and ketone substrates. The fluorescence properties of
      target compounds were studied. 

PMID- 24919957
TI  - New avenues in the directed deprotometallation of aromatics: recent advances in
      directed cupration.
AB  - Recent advances in the selective deprotometallation of aromatic reagents using
      alkali metal cuprates are reported. The ability of these synergic bases to effect
      deprotonation under the influence of a directing group is explored in the context
      of achieving new and more efficient organic transformations whilst encouraging
      greater ancillary group tolerance by the base. Developments in our understanding
      of the structural chemistry of alkali metal cuprates are reported, with both
      Gilman cuprates of the type R2CuLi and Lipshutz and related cuprates of the type
      R2Cu(X)Li2 (X = inorganic anion) elucidated and rationalised in terms of ligand
      sterics. The generation of new types of cuprate motif are introduced through the
      development of adducts between different classes of cuprate. The use of DFT
      methods to interrogate the mechanistic pathways towards deprotonative metallation
      is described. Theoretical modelling of in situ rearrangements undergone by the
      cuprate base are discussed, with a view to understanding the relationship between
      R2CuLi and R2Cu(X)Li2, their interconversion and the implications of this for
      cuprate reactivity. The advent of a new class of adduct between different cuprate
      types is developed and interpreted in terms of the options for expelling LiX from
      R2Cu(X)Li2. Applications in the field of medicinal chemistry and (hetero)arene
      derivatization are explored. 

PMID- 24919958
TI  - Coarse-grained simulations of an ionic liquid-based capacitor: II. Asymmetry in
      ion shape and charge localization.
AB  - In this work, which is a continuation of part I, we introduce a primitive model
      for an ionic liquid (IL) that can account for the planar shape of cations typical
      for ILs like imidazolium. The model consists of a spherical anion and a
      triangular cation consisting of three spheres, where one or all three vertices of
      the triangle can carry electric charge. We use molecular dynamics simulations to
      study the differential capacitance Cd of an ionic liquid confined between two
      planar electrodes. Our goal is to elucidate the complex dependence of Cd on the
      electrode potential U in terms of simple entities such as the shape and charge
      distribution of the ions. For this purpose, we compare the results from the
      current model to the results based on the models with spherical cations that
      possess asymmetry in ion valence and shape that were analyzed in detail in part I
      of this work. We show that the various possible stackings of the triangles near
      the cathode lead to noticeable new features in Cd(U) as compared to the spherical
      models. Different distributions of charges on the triangle lead to different
      preferred orientations of the cations near the cathode that are moreover
      potential dependent. 

PMID- 24919960
TI  - Temporin-SHa peptides grafted on gold surfaces display antibacterial activity.
AB  - Development of resistant bacteria onto biomaterials is a major problem leading to
      nosocomial infections. Antimicrobial peptides are good candidates for the
      generation of antimicrobial surfaces because of their broad-spectrum activity and
      their original mechanism of action (i.e. rapid lysis of the bacterial membrane)
      making them less susceptible to the development of bacterial resistance. In this
      study, we report on the covalent immobilisation of temporin-SHa on a gold surface
      modified by a thiolated self-assembled monolayer. Temporin-SHa (FLSGIVGMLGKLF
      amide) is a small hydrophobic and low cationic antimicrobial peptide with potent
      and very broad-spectrum activity against Gram-positive and Gram-negative
      bacteria, yeasts and parasites. We have analysed the influence of the binding
      mode of temporin-SHa on the antibacterial efficiency by using a covalent binding
      either via the peptide NH2 groups (random grafting of alpha- and epsilon-NH2 to
      the surface) or via its C-terminal end (oriented grafting using the analogue
      temporin-SHa-COOH). The surface functionalization was characterised by IR
      spectroscopy (polarisation modulation reflection absorption IR spectroscopy)
      while antibacterial activity against Listeria ivanovii was assessed by microscopy
      techniques, such as atomic force microscopy and scanning electron microscopy
      equipped with a field emission gun. Our results revealed that temporin-SHa
      retains its antimicrobial activity after covalent grafting. A higher amount of
      bound temporin-SHa is observed for the C-terminally oriented grafting compared
      with the random grafting (NH2 groups). Temporin-SHa therefore represents an
      attractive candidate as antimicrobial coating agent.

PMID- 24919961
TI  - Video-feedback Intervention to promote Positive Parenting adapted to Autism (VIPP
      AUTI): A randomized controlled trial.
AB  - In a randomized controlled trial, we evaluated the early intervention program
      Video-feedback Intervention to promote Positive Parenting adapted to Autism (VIPP
      AUTI) with 78 primary caregivers and their child (16-61 months) with Autism
      Spectrum Disorder. VIPP-AUTI is a brief attachment-based intervention program,
      focusing on improving parent-child interaction and reducing the child's
      individual Autism Spectrum Disorder-related symptomatology in five home visits.
      VIPP-AUTI, as compared with usual care, demonstrated efficacy in reducing
      parental intrusiveness. Moreover, parents who received VIPP-AUTI showed increased
      feelings of self-efficacy in child rearing. No significant group differences were
      found on other aspects of parent-child interaction or on child play behavior. At
      3-months follow-up, intervention effects were found on child-initiated joint
      attention skills, not mediated by intervention effects on parenting.
      Implementation of VIPP-AUTI in clinical practice is facilitated by the use of a
      detailed manual and a relatively brief training of interveners. 

PMID- 24919962
TI  - Inclusion of costs in conservation planning depends on limited datasets and
      hopeful assumptions.
AB  - Many conservation organizations use spatial prioritization to help identify
      locations in which to work. Increasingly, prioritizations seek to account for
      spatial heterogeneity in the costs of conservation, motivated in part by claims
      of large efficiency savings when these costs are included. I critically review
      the cost estimates on which such claims are based, focusing on acquisition and
      management costs associated with terrestrial protected areas. If researchers are
      to evaluate how including costs affects conservation planning outcomes,
      estimation methods need to preserve the covariation between and relative
      variation within costs and benefits of conservation activities. However, widely
      used methods for estimating costs and incorporating them into prioritizations may
      not meet these standards. For example, among relevant studies, there is
      surprisingly little attention given to the costs that conservation organizations
      actually face. Instead, there is a heavy reliance on untested proxies for
      conservation costs. Analytical shortcuts are also common. Now that debate is
      moving beyond whether to account for costs in conservation planning, it is time
      to evaluate just how we can include them to greatest effect. 

PMID- 24919963
TI  - Low-density lipoprotein cholesterol and radiotherapy-induced carotid
      atherosclerosis in subjects with head and neck cancer.
AB  - BACKGROUND: Radiotherapy (RT) is a risk factor for accelerated carotid artery
      atherosclerotic disease in subjects with head and neck cancer. However, the risk
      factors of RT-induced carotid artery remodeling are not established. This study
      aimed to investigate the effects of RT on carotid and popliteal arteries in
      subjects with head and neck cancer and to evaluate the relationship between
      baseline clinical and laboratory features and the progression of RT-induced
      atherosclerosis. FINDINGS: Eleven men (age = 57.9 +/- 6.2years) with head and
      neck cancer who underwent cervical bilateral irradiation were prospectively
      examined by clinical and laboratory analysis and by carotid and popliteal
      ultrasound before and after treatment (mean interval between the end of RT and
      the post-RT assessment = 181 +/- 47 days). No studied subject used
      hypocholesterolemic medications. Significant increases in carotid intima-media
      thickness (IMT) (0.95 +/- 0.08 vs. 0.87 +/- 0.05 mm; p < 0.0001) and carotid
      IMT/diameter ratio (0.138 +/- 0.013 vs. 0.129 +/- 0.014; p = 0.001) were observed
      after RT, while no changes in popliteal structural features were detected. In
      addition, baseline low-density lipoprotein cholesterol levels showed a direct
      correlation with RT-induced carotid IMT change (r = 0.66; p = 0.027), while no
      other studied variable exhibited a significant relationship with carotid IMT
      change. CONCLUSIONS: These results indicate that RT-induced atherosclerosis is
      limited to the irradiated area and also suggest that it may be predicted by low
      density lipoprotein cholesterol levels in subjects with head and neck cancer.

PMID- 24919964
TI  - Fast prediction of adsorption properties for platinum nanocatalysts with
      generalized coordination numbers.
AB  - Platinum is a prominent catalyst for a multiplicity of reactions because of its
      high activity and stability. As Pt nanoparticles are normally used to maximize
      catalyst utilization and to minimize catalyst loading, it is important to
      rationalize and predict catalytic activity trends in nanoparticles in simple
      terms, while being able to compare these trends with those of extended surfaces.
      The trends in the adsorption energies of small oxygen- and hydrogen-containing
      adsorbates on Pt nanoparticles of various sizes and on extended surfaces were
      analyzed through DFT calculations by making use of the generalized coordination
      numbers of the surface sites. This simple and predictive descriptor links the
      geometric arrangement of a surface to its adsorption properties. It generates
      linear adsorption-energy trends, captures finite-size effects, and provides more
      accurate descriptions than d-band centers and usual coordination numbers. Unlike
      electronic-structure descriptors, which require knowledge of the densities of
      states, it is calculated manually. Finally, it was shown that an approximate
      equivalence exists between generalized coordination numbers and d-band centers. 

PMID- 24919965
TI  - Comparison of image-guided targeted biopsies versus systematic randomized
      biopsies in the detection of prostate cancer: a systematic literature review of
      well-designed studies.
AB  - OBJECTIVE: The clinical utility of image-targeted biopsies can only be judged by
      a comparison of the current standard of systematic 10-12 core biopsy schemes. The
      aim of this review was to gather the current evidence in favor of or against
      targeted biopsies in the detection of prostate cancer based on well-designed,
      controlled studies, in order to draw clinical relevant conclusions.
      SUBJECTS/PATIENTS AND METHODS: A systematic literature review was performed
      addressing studies that compared the prostate cancer detection rates of targeted
      and systematic biopsy schemes using the imaging techniques of elastography,
      contrast-enhanced ultrasound, histoscanning and multiparametric MRI. Only well
      designed, controlled studies were included and the results summarized. RESULTS:
      All imaging techniques are associated with varying results regarding better or
      poorer detection rates relative to systematic biopsies. No technique provides a
      clear trend in favor of or against image-targeted biopsies. In almost all
      studies, the combination of targeted and systematic biopsies provided sometimes a
      substantial, increase in the detection rate relative to systematic biopsies
      alone. MRI-targeted biopsies show no advantage in the initial biopsy setting,
      whereas in the repeat biopsy setting improvements in the detection rates are
      often observed relative to systemic biopsies. CONCLUSION: Based on well-designed,
      controlled studies no clear advantage of targeted biopsies over the current
      standard of systematic biopsies can be observed. Therefore, targeted biopsies
      cannot replace systematic biopsies in the diagnosis of prostate cancer. In all
      indications, the combination of systematic and targeted biopsy schemes provides
      the highest detection rate.

PMID- 24919966
TI  - Reply: Retinopathy, histidine-rich protein-2 and perfusion pressure in cerebral
      malaria.

PMID- 24919968
TI  - Retinopathy, histidine-rich protein-2 and perfusion pressure in cerebral malaria.

PMID- 24919967
TI  - Connexin-43 induces chemokine release from spinal cord astrocytes to maintain
      late-phase neuropathic pain in mice.
AB  - Accumulating evidence suggests that spinal cord astrocytes play an important role
      in neuropathic pain sensitization by releasing astrocytic mediators (e.g.
      cytokines, chemokines and growth factors). However, it remains unclear how
      astrocytes control the release of astrocytic mediators and sustain late-phase
      neuropathic pain. Astrocytic connexin-43 (now known as GJ1) has been implicated
      in gap junction and hemichannel communication of cytosolic contents through the
      glial syncytia and to the extracellular space, respectively. Connexin-43 also
      plays an essential role in facilitating the development of neuropathic pain, yet
      the mechanism for this contribution remains unknown. In this study, we
      investigated whether nerve injury could upregulate connexin-43 to sustain late
      phase neuropathic pain by releasing chemokine from spinal astrocytes. Chronic
      constriction injury elicited a persistent upregulation of connexin-43 in spinal
      astrocytes for >3 weeks. Spinal (intrathecal) injection of carbenoxolone (a non
      selective hemichannel blocker) and selective connexin-43 blockers (connexin-43
      mimetic peptides (43)Gap26 and (37,43)Gap27), as well as astroglial toxin but not
      microglial inhibitors, given 3 weeks after nerve injury, effectively reduced
      mechanical allodynia, a cardinal feature of late-phase neuropathic pain. In
      cultured astrocytes, TNF-alpha elicited marked release of the chemokine CXCL1,
      and the release was blocked by carbenoxolone, Gap26/Gap27, and connexin-43 small
      interfering RNA. TNF-alpha also increased connexin-43 expression and hemichannel
      activity, but not gap junction communication in astrocyte cultures prepared from
      cortices and spinal cords. Spinal injection of TNF-alpha-activated astrocytes was
      sufficient to induce persistent mechanical allodynia, and this allodynia was
      suppressed by CXCL1 neutralization, CXCL1 receptor (CXCR2) antagonist, and
      pretreatment of astrocytes with connexin-43 small interfering RNA. Furthermore,
      nerve injury persistently increased excitatory synaptic transmission (spontaneous
      excitatory postsynaptic currents) in spinal lamina IIo nociceptive synapses in
      the late phase, and this increase was suppressed by carbenoxolone and Gap27, and
      recapitulated by CXCL1. Together, our findings demonstrate a novel mechanism of
      astrocytic connexin-43 to enhance spinal cord synaptic transmission and maintain
      neuropathic pain in the late-phase via releasing chemokines. 

PMID- 24919969
TI  - Visual short-term memory deficits associated with GBA mutation and Parkinson's
      disease.
AB  - Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene
      are at significantly high risk of developing Parkinson's disease with cognitive
      deficit. We examined whether visual short-term memory impairments, long
      associated with patients with Parkinson's disease, are also present in GBA
      positive individuals-both with and without Parkinson's disease. Precision of
      visual working memory was measured using a serial order task in which
      participants observed four bars, each of a different colour and orientation,
      presented sequentially at screen centre. Afterwards, they were asked to adjust a
      coloured probe bar's orientation to match the orientation of the bar of the same
      colour in the sequence. An additional attentional 'filtering' condition tested
      patients' ability to selectively encode one of the four bars while ignoring the
      others. A sensorimotor task using the same stimuli controlled for perceptual and
      motor factors. There was a significant deficit in memory precision in GBA
      positive individuals-with or without Parkinson's disease-as well as GBA-negative
      patients with Parkinson's disease, compared to healthy controls. Worst recall was
      observed in GBA-positive cases with Parkinson's disease. Although all groups were
      impaired in visual short-term memory, there was a double dissociation between
      sources of error associated with GBA mutation and Parkinson's disease. The
      deficit observed in GBA-positive individuals, regardless of whether they had
      Parkinson's disease, was explained by a systematic increase in interference from
      features of other items in memory: misbinding errors. In contrast, impairments in
      patients with Parkinson's disease, regardless of GBA status, was explained by
      increased random responses. Individuals who were GBA-positive and also had
      Parkinson's disease suffered from both types of error, demonstrating the worst
      performance. These findings provide evidence for dissociable signature deficits
      within the domain of visual short-term memory associated with GBA mutation and
      with Parkinson's disease. Identification of the specific pattern of cognitive
      impairment in GBA mutation versus Parkinson's disease is potentially important as
      it might help to identify individuals at risk of developing Parkinson's disease. 

PMID- 24919970
TI  - Music, reward and frontotemporal dementia.

PMID- 24919971
TI  - Large scale screening of neural signatures of consciousness in patients in a
      vegetative or minimally conscious state.
AB  - In recent years, numerous electrophysiological signatures of consciousness have
      been proposed. Here, we perform a systematic analysis of these
      electroencephalography markers by quantifying their efficiency in differentiating
      patients in a vegetative state from those in a minimally conscious or conscious
      state. Capitalizing on a review of previous experiments and current theories, we
      identify a series of measures that can be organized into four dimensions: (i)
      event-related potentials versus ongoing electroencephalography activity; (ii)
      local dynamics versus inter-electrode information exchange; (iii) spectral
      patterns versus information complexity; and (iv) average versus fluctuations over
      the recording session. We analysed a large set of 181 high-density
      electroencephalography recordings acquired in a 30 minutes protocol. We show that
      low-frequency power, electroencephalography complexity, and information exchange
      constitute the most reliable signatures of the conscious state. When combined,
      these measures synergize to allow an automatic classification of patients' state
      of consciousness. 

PMID- 24919972
TI  - High frequency oscillations are associated with cognitive processing in human
      recognition memory.
AB  - High frequency oscillations are associated with normal brain function, but also
      increasingly recognized as potential biomarkers of the epileptogenic brain. Their
      role in human cognition has been predominantly studied in classical gamma
      frequencies (30-100 Hz), which reflect neuronal network coordination involved in
      attention, learning and memory. Invasive brain recordings in animals and humans
      demonstrate that physiological oscillations extend beyond the gamma frequency
      range, but their function in human cognitive processing has not been fully
      elucidated. Here we investigate high frequency oscillations spanning the high
      gamma (50-125 Hz), ripple (125-250 Hz) and fast ripple (250-500 Hz) frequency
      bands using intracranial recordings from 12 patients (five males and seven
      females, age 21-63 years) during memory encoding and recall of a series of
      affectively charged images. Presentation of the images induced high frequency
      oscillations in all three studied bands within the primary visual, limbic and
      higher order cortical regions in a sequence consistent with the visual processing
      stream. These induced oscillations were detected on individual electrodes
      localized in the amygdala, hippocampus and specific neocortical areas, revealing
      discrete oscillations of characteristic frequency, duration and latency from
      image presentation. Memory encoding and recall significantly modulated the number
      of induced high gamma, ripple and fast ripple detections in the studied
      structures, which was greater in the primary sensory areas during the encoding
      (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association
      areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images.
      Furthermore, the induced high gamma, ripple and fast ripple responses
      discriminated the encoded and the affectively charged images. In summary, our
      results show that high frequency oscillations, spanning a wide range of
      frequencies, are associated with memory processing and generated along
      distributed cortical and limbic brain regions. These findings support an
      important role for fast network synchronization in human cognition and extend our
      understanding of normal physiological brain activity during memory processing. 

PMID- 24919973
TI  - On the nature of seizure dynamics.
AB  - Seizures can occur spontaneously and in a recurrent manner, which defines
      epilepsy; or they can be induced in a normal brain under a variety of conditions
      in most neuronal networks and species from flies to humans. Such universality
      raises the possibility that invariant properties exist that characterize seizures
      under different physiological and pathological conditions. Here, we analysed
      seizure dynamics mathematically and established a taxonomy of seizures based on
      first principles. For the predominant seizure class we developed a generic model
      called Epileptor. As an experimental model system, we used ictal-like discharges
      induced in vitro in mouse hippocampi. We show that only five state variables
      linked by integral-differential equations are sufficient to describe the onset,
      time course and offset of ictal-like discharges as well as their recurrence. Two
      state variables are responsible for generating rapid discharges (fast time
      scale), two for spike and wave events (intermediate time scale) and one for the
      control of time course, including the alternation between 'normal' and ictal
      periods (slow time scale). We propose that normal and ictal activities coexist: a
      separatrix acts as a barrier (or seizure threshold) between these states. Seizure
      onset is reached upon the collision of normal brain trajectories with the
      separatrix. We show theoretically and experimentally how a system can be pushed
      toward seizure under a wide variety of conditions. Within our experimental model,
      the onset and offset of ictal-like discharges are well-defined mathematical
      events: a saddle-node and homoclinic bifurcation, respectively. These
      bifurcations necessitate a baseline shift at onset and a logarithmic scaling of
      interspike intervals at offset. These predictions were not only confirmed in our
      in vitro experiments, but also for focal seizures recorded in different
      syndromes, brain regions and species (humans and zebrafish). Finally, we
      identified several possible biophysical parameters contributing to the five state
      variables in our model system. We show that these parameters apply to specific
      experimental conditions and propose that there exists a wide array of possible
      biophysical mechanisms for seizure genesis, while preserving central invariant
      properties. Epileptor and the seizure taxonomy will guide future modeling and
      translational research by identifying universal rules governing the initiation
      and termination of seizures and predicting the conditions necessary for those
      transitions. 

PMID- 24919975
TI  - Salpingectomy for tubal ectopic pregnancy is appropriate in the presence of
      healthy-looking contralateral tube.

PMID- 24919974
TI  - Secondary prevention medication after myocardial infarction: persistence in
      elderly people over the course of 1 year.
AB  - AIMS: Persistent use of guideline-recommended drugs after acute myocardial
      infarction (AMI) is frequently reported to be inadequate in the elderly and
      scarce knowledge exists about factors that influence persistence in outpatient
      care. Our aim was to evaluate drug use and its predictors in survivors of AMI
      above 64 years from hospital discharge to 1-year post-AMI. METHODS: In a single
      centre randomised controlled trial, discharge medication of 259 patients with AMI
      was obtained from medical records at hospital stay. Follow-up drug use and use of
      the healthcare system were self-reported to study nurses over 1 year in 3-month
      intervals. Predictors for persistence were modelled with multivariate logistic
      regression analysis considering demographics, co-morbidities and treatment
      characteristics. RESULTS: At discharge, 99.2 % of the patients used anti
      platelets, 86.5 % beta blockers, 95.0 % statins and 90.4 % angiotensin-converting
      enzyme inhibitors or angiotensin receptor blockers. Use of the combination of all
      four drug classes decreased from discharge to 1 year post-AMI from 74.1 to 37.8 %
      and was significantly reduced by age >=75 years (odds ratio [OR] 0.49; 95 %
      confidence interval [CI] 0.29-0.85) and ten or more visits with general
      practitioners (GPs) over 1 year (OR 0.29; 95 % CI 0.17-0.51). Persistence from
      month 3 to 12 was significantly associated with drug use at discharge for the
      single drug classes, but not for the drug combination. CONCLUSION: Older age and
      frequent GP visits are associated with decreased use of the guideline-recommended
      drug combination after AMI. Further research is needed to specify underlying
      reasons and develop measures to improve persistence.

PMID- 24919976
TI  - Dexamethasone may be a viable alternative to prednisone/prednisolone for the
      treatment of acute asthma exacerbation in the paediatric emergency department.

PMID- 24919977
TI  - Radical prostatectomy reduces prostate cancer-specific mortality among men with
      intermediate-grade disease, but provides minimal benefit for men with low-grade
      and high-grade disease.

PMID- 24919978
TI  - The use of artificial crabs for testing predatory behavior and health in the
      octopus.
AB  - The willingness of the cephalopod mollusc Octopus vulgaris to attack a live crab
      is traditionally used as a method to assess the overall health and welfare of
      octopuses in the laboratory. This method requires placing a crab in the home tank
      of an animal, measuring the time (latency) taken for the octopus to initiate an
      attack and withdrawing the crab immediately prior to capture. The same crab is
      commonly used to assess multiple octopuses as part of daily welfare assessment.
      Growing concern for the welfare of crustaceans and a review of all laboratory
      practices for the care and welfare of cephalopods following the inclusion of this
      taxon in 2010/63/EU prompted a study of the utility of an artificial crab to
      replace a live crab in the assessment of octopus health. On consecutive days O.
      vulgaris (N=21) were presented with a live, a dead or an artificial crab, and the
      latency to attack measured. Despite differences in the predatory performance
      towards the three different crab alternatives, octopuses readily attacked the
      artificial (and the dead) crab, showing that they can generalize and respond
      appropriately towards artificial prey. Researchers should consider using an
      artificial crab to replace the use of a live crab as part of the routine health
      assessment of O. vulgaris.

PMID- 24919979
TI  - Analysis of secondary outcomes in nested case-control study designs.
AB  - One of the main perceived advantages of using a case-cohort design compared with
      a nested case-control design in an epidemiologic study is the ability to evaluate
      with the same subcohort outcomes other than the primary outcome of interest. In
      this paper, we show that valid inferences about secondary outcomes can also be
      achieved in nested case-control studies by using the inclusion probability
      weighting method in combination with an approximate jackknife standard error that
      can be computed using existing software. Simulation studies demonstrate that when
      the sample size is sufficient, this approach yields valid type 1 error and
      coverage rates for the analysis of secondary outcomes in nested case-control
      designs. Interestingly, the statistical power of the nested case-control design
      was comparable with that of the case-cohort design when the primary and secondary
      outcomes were positively correlated. The proposed method is illustrated with the
      data from a cohort in Cardiovascular Health Study to study the association of C
      reactive protein levels and the incidence of congestive heart failure.

PMID- 24919980
TI  - Rituximab for treatment of inhibitors in haemophilia A. A Phase II study.
AB  - The development of antibodies against infused factor VIII (FVIII) in patients
      with haemophilia A is a serious complication leading to poorly controlled
      bleeding and increased morbidity. No treatment has been proven to reduce high
      titre antibodies in patients who fail immune tolerance induction or are not
      candidates for it. The Rituximab for the Treatment of Inhibitors in Congenital
      Hemophilia A (RICH) study was a phase II trial to assess whether rituximab can
      reduce anamnestic FVIII antibody (inhibitor) titres. Male subjects with severe
      congenital haemophilia A and an inhibitor titre >=5 Bethesda Units/ml (BU)
      following a FVIII challenge infusion received rituximab 375 mg/m2 weekly for
      weeks 1 through 4. Post-rituximab inhibitor titres were measured monthly from
      week 6 through week 22 to assess treatment response. Of 16 subjects who received
      at least one dose of rituximab, three (18.8%) met the criteria for a major
      response, defined as a fall in inhibitor titre to <5 BU, persisting after FVIII
      re-challenge. One subject had a minor response, defined as a fall in inhibitor
      titre to <5 BU, increasing to 5-10 BU after FVIII re-challenge, but <50% of the
      original peak inhibitor titre. Rituximab is useful in lowering inhibitor levels
      in patients, but its effect as a solo treatment strategy is modest. Future
      studies are indicated to determine the role of rituximab as an adjunctive therapy
      in immune tolerisation strategies. 

PMID- 24919983
TI  - Differential diagnosis of pancreatic serous oligocystic adenoma and mucinous
      cystic neoplasm with spectral CT imaging: initial results.
AB  - AIM: To investigate the imaging characteristics of pancreatic serous oligocystic
      adenoma (SOA) and mucinous cystic neoplasms (MCNs) using spectral computed
      tomography (CT) and to evaluate whether quantitative information derived from
      spectral imaging can improve the differential diagnosis of these diseases.
      MATERIALS AND METHODS: From February 2010 to June 2013, 44 patients (24 SOAs and
      20 MCNs) who underwent spectral CT imaging were included in the study.
      Conventional characteristics and quantitative parameters were compared between
      the two disease groups. Logistic regression was used for multiparametric
      analysis. The receiver-operating characteristic curve was used to evaluate the
      diagnostic performance of single parameter and multiparametric analysis. Two
      radiologists diagnosed the diseases blinded and independently, without and with
      the information of the statistical analysis. RESULTS: Tumour location, contour,
      size, and monochromatic CT values at 40 keV to 70 keV, iodine concentration, and
      effective atomic number (effective-Z) in the late arterial phase were the
      independent factors correlated with category. Multiparametric analysis with
      logistic regression showed that tumour size, location, and contour were the most
      effective variations, and obtained an area under the ROC curve (AUC) of 0.934.
      With the knowledge of statistical analysis, the accuracy of the first reader
      increased from 70.5% to 86.4%, and the accuracy of the second reader increased
      from 81.8% to 90.9%. CONCLUSIONS: Although CT spectral imaging provided
      additional information and multiparametric analysis obtained better performance
      than single-parameter analysis in differentiating MCNs from SOAs, multiparametric
      analysis with the combination of quantitative parameters derived from CT spectral
      imaging did not improve the diagnostic performance. Tumour size, location, and
      contour played an important role in differentiating MCNs from SOAs.

PMID- 24919981
TI  - Genetic control of functional traits related to photosynthesis and water use
      efficiency in Pinus pinaster Ait. drought response: integration of genome
      annotation, allele association and QTL detection for candidate gene
      identification.
AB  - BACKGROUND: Understanding molecular mechanisms that control photosynthesis and
      water use efficiency in response to drought is crucial for plant species from dry
      areas. This study aimed to identify QTL for these traits in a Mediterranean
      conifer and tested their stability under drought. RESULTS: High density linkage
      maps for Pinus pinaster were used in the detection of QTL for photosynthesis and
      water use efficiency at three water irrigation regimes. A total of 28 significant
      and 27 suggestive QTL were found. QTL detected for photochemical traits accounted
      for the higher percentage of phenotypic variance. Functional annotation of genes
      within the QTL suggested 58 candidate genes for the analyzed traits. Allele
      association analysis in selected candidate genes showed three SNPs located in a
      MYB transcription factor that were significantly associated with efficiency of
      energy capture by open PSII reaction centers and specific leaf area. CONCLUSIONS:
      The integration of QTL mapping of functional traits, genome annotation and allele
      association yielded several candidate genes involved with molecular control of
      photosynthesis and water use efficiency in response to drought in a conifer
      species. The results obtained highlight the importance of maintaining the
      integrity of the photochemical machinery in P. pinaster drought response.

PMID- 24919984
TI  - Neural correlates of attention to emotional facial expressions in dysphoria.
AB  - The present study investigated whether dysphoric individuals have a difficulty in
      disengaging attention from negative stimuli and/or reduced attention to positive
      information. Sad, neutral and happy facial stimuli were presented in an attention
      shifting task to 18 dysphoric and 18 control participants. Reaction times to
      neutral shapes (squares and diamonds) and the event-related potentials to
      emotional faces were recorded. Dysphoric individuals did not show impaired
      attentional disengagement from sad faces or facilitated disengagement from happy
      faces. Right occipital lateralisation of P100 was absent in dysphoric
      individuals, possibly indicating reduced attention-related sensory facilitation
      for faces. Frontal P200 was largest for sad faces among dysphoric individuals,
      whereas controls showed larger amplitude to both sad and happy as compared with
      neutral expressions, suggesting that dysphoric individuals deployed early
      attention to sad, but not happy, expressions. Importantly, the results were
      obtained controlling for the participants' trait anxiety. We conclude that at
      least under some circumstances the presence of depressive symptoms can modulate
      early, automatic stages of emotional processing. 

PMID- 24919982
TI  - Models of consent to return of incidental findings in genomic research.
AB  - Genomic research-including whole genome sequencing and whole exome sequencing-has
      a growing presence in contemporary biomedical investigation. The capacity of
      sequencing techniques to generate results that go beyond the primary aims of the
      research-historically referred to as "incidental findings"-has generated
      considerable discussion as to how this information should be handled-that is,
      whether incidental results should be returned, and if so, which ones.Federal
      regulations governing most human subjects research in the United States require
      the disclosure of "the procedures to be followed" in the research as part of the
      informed consent process. It seems reasonable to assume-and indeed, many
      commentators have concluded-that genomic investigators will be expected to inform
      participants about, among other procedures, the prospect that incidental findings
      will become available and the mechanisms for dealing with them. Investigators,
      most of whom will not have dealt with these issues before, will face considerable
      challenges in framing meaningful disclosures for research participants.To help in
      this task, we undertook to identify the elements that should be included in the
      informed consent process related to incidental findings. We did this by surveying
      a large number of genomic researchers (n = 241) and by conducting in-depth
      interviews with a smaller number of researchers (n = 28) and genomic research
      participants (n = 20). Based on these findings, it seems clear to us that routine
      approaches to informed consent are not likely to be effective in genomic research
      in which the prospect of incidental findings exists. Ensuring that participants'
      decisions are informed and meaningful will require innovative approaches to
      dealing with the consent issue. We have identified four prototypical models of a
      consent process for return of incidental findings. 

PMID- 24919985
TI  - Anxiolytic-like effect of Illicium verum fruit oil, trans-anethole and related
      compounds in mice.
AB  - The fruit of Illicium verum Hook. f. (star anise) is used by many as a spice. The
      fragrance of I. verum fruit is characteristically anise-like. In this study,
      hexane-extracted I. verum fruit oil (IVO), trans-anethole as the main component,
      and related compounds (propiophenone, 4'-methoxy-propiophenone, trans-beta
      methylstyrene) were analyzed in order to clarify the emotional effect of inhaling
      the fragrance of I. verum fruit. As a result, although 4 MUL/L air IVO did not
      exhibit an anxiolytic-like effect, 1 MUL/L air trans-anethole exhibited a
      significant effect (p < 0.05). Moreover, the anxiolytic-like effect of 1 MUL/L
      air trans-anethole was significantly greater than 1 MUL/L air propiophenone and 1
      MUL/L air 4'-methoxy-propiophenone (p < 0.05). Thus, the anxiolytic-like effect
      of trans-anethole was confirmed, and it is proposed that the methoxyl group and 1
      propenyl group in the para position of the benzene ring are necessary for the
      effect.

PMID- 24919986
TI  - The influence of focal spot size, shape, emission profile and position on field
      coverage in a Gulmay D3300 Kilovoltage X-ray therapy unit.
AB  - An important characteristic of kilovoltage therapy is the narrow penumbra
      obtainable with a well designed collimator system. A graphical illustration of
      applicator geometry is used to show that undesirable penumbral broadening and
      consequent reduction of field coverage could result if the upper aperture in an
      applicator is smaller than a critical size or if the applicator is not
      sufficiently well aligned with the focal spot. This concept is applied in an
      investigation of the formation of penumbra in the Gulmay D3300, in which the
      influence of the focal spot size, shape and emission profile, obtained from an
      image of the focal spot produced using a pin-hole in a sheet of lead, is
      elucidated. The effective focal spot of the Varian X-ray tube was observed to be
      rectangular, significantly longer in the front-back direction (6 mm) than in the
      anode-cathode direction (3.5 mm) and quite non-uniform in emission intensity over
      its length, with pronounced hot-spots at each end. It is shown that this results
      in a penumbra which is slightly broadened in the front-back direction when the
      alignment is perfect, but significantly broadened asymmetrically even when the
      alignment just meets the manufacturer's stated tolerance. Consequently the
      alignment, which is performed with an alignment jig supplied by the manufacturer,
      needs to be very precise to obtain acceptable field coverage, which needs to be
      checked following an X-ray tube change. 

PMID- 24919987
TI  - The Medicare readmission measure for surgical hospitalizations: awful or just not
      very good?

PMID- 24919988
TI  - Arsenic speciation in rice-based food for adults with celiac disease.
AB  - Celiac disease (CD) may affect up to 1% of the Western population. It is a
      disease whose diagnosis has been made mainly in childhood, but now the profile
      has changed, with one out of five newly diagnosed individuals being over 65 years
      old. The only treatment for this population is a gluten-free diet. Therefore, the
      objective of this study was to analyse the occurrence of arsenic (As) in gluten
      free products, basically those rice-based, intended for celiac adult consumers.
      The current study demonstrated that these rice-based products contained important
      contents of total arsenic (t-As) (up to 120 MUg kg(-1)) and inorganic arsenic (i
      As) (up to 85.8 MUg kg(-1)). It was estimated that the contents of t-As and i-As
      in rice used as the main ingredient of these foods were as high as 235 and 198
      MUg kg(-1), respectively. The estimated daily intake of i-As was 0.46 and 0.45
      MUg kg(-1) bw in women and men of 58 and 75 kg of body weight (bw), respectively.
      These values indicate that a health risk to these consumers cannot be excluded.
      Finally, legislation is needed to delimit the safety intake by health agencies
      and to improve the labelling of these special rice-based foods for celiac adult
      consumers. The label should include information about percentage, geographical
      origin and cultivar of the rice used; besides and if companies want to clearly
      prove the safety of their products, the exact content of i-As should also be
      included. 

PMID- 24919989
TI  - Direct enantioselective three-component synthesis of optically active
      propargylamines in water.
AB  - An enantioselective three-component reaction of aldehydes, amines, and alkynes in
      water by using a bis(imidazoline)-Cu(I) catalysts having a hydrophobic
      substituent and sodium dodecyl sulfate as a surfactant was developed. The
      reaction was applied to a broad range of aldehydes and alkynes to give optically
      active propargylamines with excellent yields (up to 99 %) and enantiomeric
      excesses (up to 99 % ee). 

PMID- 24919990
TI  - Conformational preferences of peptide-peptoid hybrid oligomers.
AB  - Peptomers are oligomeric molecules composed of both alpha-amino acids and N
      substituted glycine monomers, thus creating a hybrid of peptide and peptoid
      units. Peptomers have been used in several applications such as antimicrobials,
      protease inhibitors, and antibody mimics. Despite the considerable promise of
      peptomers as chemically diverse molecular scaffolds, we know little about their
      conformational tendencies. This lack of knowledge limits the ability to implement
      computational approaches for peptomer design. Here we computationally evaluate
      the local structural propensities of the peptide-peptoid linkage. We find some
      general similarities between the peptide residue conformational preferences and
      the Ramachandran distribution of residues that precede proline in folded protein
      structures. However, there are notable differences. For example, several beta
      turn motifs are disallowed when the i+2 residue is also a peptoid monomer.
      Significantly, the lowest energy geometry, when dispersion forces are accounted
      for, corresponds to a "cis-Pro touch-turn" conformation, an unusual turn motif
      that has been observed at protein catalytic centers and binding sites. The
      peptomer touch-turn thus represents a useful design element for the construction
      of folded oligomers capable of molecular recognition and as modules in the
      assembly of structurally complex peptoid-protein hybrid macromolecules.

PMID- 24919991
TI  - The role of gender, values, and culture in adolescent bystanders' strategies.
AB  - We examined the relationship between adolescent bystanders' strategies for
      intervening in the bullying-like situation and their gender, values, and cultural
      origin. The sample consisted of 682 Estonian and Russian-Estonian adolescents (M
      age = 13.02 years). They were shown a video of a bullying-like situation with a
      non-intervening adult bystander and asked to describe what they would do if they,
      instead of the adult, witnessed that situation. Only 10% said that they would not
      intervene. Girls were more likely than boys to suggest multiple actions.
      Adolescents who valued conformity were less likely to propose using physical
      aggression. Doing nothing was less likely suggested by those who placed more
      importance on conformity and less on power. Estonian adolescents were more likely
      than their Russian-Estonian peers to suggest finding out what is going on, and
      less likely to say that they would do nothing. The findings suggest that although
      most adolescents express willingness to help the victim, they might not actually
      know how to intervene. 

PMID- 24919992
TI  - Emotion dysregulation and drinking to cope as predictors and consequences of
      alcohol-involved sexual assault: examination of short-term and long-term risk.
AB  - The present study examined emotion dysregulation, coping drinking motives, and
      alcohol-related problems as predictors and consequences of alcohol-involved
      sexual assault (AISA). A convenience sample of 424 college women completed
      confidential surveys on paper and online. Data were collected at baseline (T1),
      weekly for 10 weeks (T2-10), and at 1 year (T11). The cross-sectional and
      longitudinal associations among variables were examined in a cross-lagged panel
      model. Within each time point, all variables were correlated. Drinking to cope
      and emotion dysregulation predicted AISA in the short term (within 10 weeks),
      alcohol problems increased risk for AISA in the long term (within 1 year), and
      AISA history predicted AISA revictimization regardless of time frame. Drinking to
      cope and alcohol-related problems predicted future victimization, but their
      impact seems to fluctuate over time. Coping drinking motives were both a
      predictor and consequence of AISA, suggesting a cyclical pattern. However,
      additional analyses indicated that coping drinking motives and alcohol problems
      might act as suppressors in the model. Overall, findings indicate that
      interventions focused on improving emotion regulation skills may decrease short
      term risk for AISA. 

PMID- 24919993
TI  - Experience of domestic violence and acceptance of intimate partner violence among
      out-of-school adolescent girls in Iwaya Community, Lagos State.
AB  - Gender-based domestic violence (DV) comes at great costs to the victims and
      society at large. Yet, many women hold the view that intimate partner violence
      (IPV) against women is appropriate behavior. This study aimed at exploring the
      nexus of experience of different forms of DV and acceptance of IPV as appropriate
      behavior. Using data from a survey of 480 out-of-school adolescent girls, the
      researcher shows that psychological abuse is a significant predictor of approval
      of DV resulting from the wife's failure to make food available for her husband
      with victims of abuse approving of violence against women. Conversely, victims of
      sexual abuse, more than nonvictims, disapproved of wife beating resulting from
      the wife going out without informing the husband. The implications of the
      findings are discussed and the study recommends deconstructing women's negative
      beliefs upon which DV rests. 

PMID- 24919994
TI  - Women's perspectives on the context of violence and role of police in their
      intimate partner violence arrest experiences.
AB  - Intimate partner violence (IPV) accounts for up to 50% of all calls to police. In
      an effort to standardize arrest criteria, mandatory arrest laws were established.
      It is unclear whether subsequent increased rates of female arrest are due to
      greater recognition of female IPV perpetrators or of women acting in self
      defense. This study aims to understand the context and consequences of IPV
      related arrest from perspectives of women arrested in a single metropolitan area.
      Semi-structured qualitative interviews were conducted with women arrested and
      court-ordered to attend IPV education groups at a women's shelter in the
      Northeast United States. Interviews addressed circumstances surrounding arrest,
      experience with past violence, and reasoning regarding use of partner violence.
      Two researchers independently coded transcripts and met to iteratively refine the
      code and review transcripts for themes. Eighteen women were interviewed. Major
      themes that emerged were as follows: (a) Women's use of violence occurred within
      the context of their own victimization; (b) the arrest included a complex
      interplay between subject, partner, and police; (c) women perceived police arrest
      decisions to be based on a limited understanding of context; and (d) women
      experienced both positive and negative consequences of arrest. Many relationships
      did not fall under the traditional victim/perpetrator construct. Rather, women's
      use of violence evolved, influenced by prior experiences with violence. More
      appropriate methods must be developed for making arrest decisions, guiding
      justice system responses, and developing interventions for couples experiencing
      IPV. Recognition that women's use of partner violence often represented either a
      retaliatory or self-defensive gesture within the context of prior victimization
      suggests that victims' interventions should not only focus on empowerment but
      also provide skills and strategies to avoid temptation to adopt aggression as a
      primary method of self-protection. 

PMID- 24919995
TI  - Intimate partner violence victims as mothers: their messages and strategies for
      communicating with children to break the cycle of violence.
AB  - Children whose mothers are victims of intimate partner violence (IPV) are at
      increased risk of adverse health and psychosocial consequences, including
      becoming victims or perpetrators of violence in their own relationships. This
      study aimed to understand the role mothers may play in preventing the
      perpetuation of violence in their children's lives. We performed semistructured
      interviews with 18 IPV victims who are mothers and were living at the Women's
      Center & Shelter of Greater Pittsburgh from July through November 2011. We sought
      to understand how they communicate with their children about IPV and
      relationships. These mothers described a desire to explain their IPV experience
      and offer advice about avoiding violence in relationships. As foundations for
      these discussions, they emphasized the importance of close relationships and open
      communication with their children. Although mothers are interested in talking
      about IPV and relationships and identify communication strategies for doing so,
      many have never discussed these topics with their children. These mothers need
      and want an intervention to help them learn how to communicate with their
      children to promote healthy relationships. Development of a program to facilitate
      communication between IPV victims and their children could create an important
      tool to empower mothers to break the cross-generational cycle of domestic
      violence. 

PMID- 24919996
TI  - A typology of community violence perpetration and victimization among adults with
      mental illnesses.
AB  - The primary objective of this article was to evaluate the overlap between
      community violence perpetration and victimization in a large, heterogeneous
      sample of adults with mental illnesses (N = 4,474). We also explored participant
      characteristics differentiating four categories of perpetration and
      victimization: non-victim/non-perpetrators, victims only, perpetrators only, and
      victim-perpetrators. Results indicated that adults with mental illnesses were
      unlikely to report violent outcomes but, when they did, were more likely to
      report perpetration and victimization, rather than perpetration alone. In
      addition, bivariate and multivariable analyses showed that sex, age,
      race/ethnicity, and primary diagnosis differed across categories. Victim
      perpetrators, for example, were more likely to be young, Black, and have a
      primary diagnosis of bipolar disorder, major depressive disorder, substance use
      disorder, or "other." Altogether, our findings provide evidence for a victim
      perpetrator overlap in this population and suggest that preventive measures
      targeting violence and victimization may be more effective than those with
      separate strategies for each. 

PMID- 24919997
TI  - The association between substance use and intimate partner violence within Black
      male same-sex relationships.
AB  - Compared with the extant research on heterosexual intimate partner violence (IPV)
      including the knowledge base on alcohol and illicit drug use as predictors of
      such IPV-there is a paucity of studies on IPV among men who have sex with men
      (MSM), especially Black MSM. This study investigates the prevalence of
      experiencing and perpetrating IPV among a sample of Black MSM couples and
      examines whether heavy drinking and/or illicit substance use is associated with
      IPV. We conducted a secondary analysis on a data set from 74 individuals
      (constituting 37 Black MSM couples) screened for inclusion in a couple-based HIV
      prevention pilot study targeting methamphetamine-involved couples. More than one
      third (n= 28, 38%) reported IPV at some point with the current partner: 24 both
      experiencing and perpetrating, 2 experiencing only, and 2 perpetrating only. IPV
      in the past 30 days was reported by 21 (28%) of the participants: 18 both
      experiencing and perpetrating, 1 experiencing only, and 2 perpetrating only.
      Heavy drinking and methamphetamine use each was associated significantly with
      experiencing and perpetrating IPV throughout the relationship as well as in the
      past 30 days. Rock/crack cocaine use was significantly associated with any
      history of experiencing and perpetrating IPV. Altogether, IPV rates in this
      sample of Black MSM couples equal or exceed those observed among women victimized
      by male partners as well as the general population of MSM. This exploratory study
      points to a critical need for further efforts to understand and address IPV among
      Black MSM. Similar to heterosexual IPV, results point to alcohol and illicit drug
      use treatment as important avenues to improve the health and social well-being of
      Black MSM. 

PMID- 24919998
TI  - The normalization of sibling violence: does gender and personal experience of
      violence influence perceptions of physical assault against siblings?
AB  - Despite its pervasive and detrimental nature, sibling violence (SV) remains
      marginalized as a harmless and inconsequential form of familial aggression. The
      present study investigates the extent to which perceptions of SV differ from
      those of other types of interpersonal violence. A total of 605 respondents (197
      males, 408 females) read one of four hypothetical physical assault scenarios that
      varied according to perpetrator-victim relationship type (i.e., sibling vs.
      dating partner vs. peer vs. stranger) before completing a series of 24
      attribution items. Respondents also reported on their own experiences of
      interpersonal violence during childhood. Exploratory factor analysis reduced 23
      attribution items to three internally reliable factors reflecting perceived
      assault severity, victim culpability, and victim resistance ratings. A 4 * 2
      MANCOVA-controlling for respondent age-revealed several significant effects.
      Overall, males deemed the assault less severe and the victim more culpable than
      did females. In addition, the sibling assault was deemed less severe compared to
      assault on either a dating partner or a stranger, with the victim of SV rated
      just as culpable as the victim of dating, peer, or stranger-perpetrated violence.
      Finally, respondents with more (frequent) experiences of childhood SV
      victimization perceived the hypothetical SV assault as being less severe, and
      victim more culpable, than respondents with no SV victimization. Results are
      discussed in the context of SV normalization. Methodological limitations and
      applications for current findings are also outlined. 

PMID- 24919999
TI  - Risk levels, treatment duration, and drop out in a clinically composed outpatient
      sex offender treatment group.
AB  - Previous research in the Netherlands documented that clinical judgment may yield
      a substantial amount of treatment referrals for sexual offenders that are
      inconsistent with actuarial risk assessment and the Risk Need Responsivity (RNR)
      principles. The present study tested the risk level distribution of a high
      intensity, open-format outpatient treatment group. Eighty patients were enrolled
      during a 620-week period, and their STATIC-99R risk levels were retrospectively
      determined. The distribution of risk levels in this treatment group did not
      differ from the distribution of a representative sample of sex offenders referred
      to outpatient treatment in the Netherlands between 1996 and 2002 (n = 145), nor
      from the combined Canadian samples (n = 2011) used to assess STATIC-99R normative
      percentile. These findings suggest that no selection in terms of actuarial risk
      level occurred between conviction and treatment, leading to over-inclusion of low
      risk offenders in this high-intensity outpatient treatment group. It is concluded
      that the standard use of structured risk assessment for the compilation of
      treatment groups may improve both the effectiveness and efficiency of sex
      offender treatment in the Netherlands. 

PMID- 24920000
TI  - Development and validation of the belief in Female Sexual Deceptiveness scale.
AB  - This article describes the development of a scale measuring the extent of men's
      belief in female sexual deceptiveness. This belief has been postulated as a
      component of hostile masculinity and a precursor to more serious sexual-assault
      facilitating cognitions, though it has not yet been studied empirically. From a
      final pool of 22 items, the 14-item Belief in Female Sexual Deceptiveness (BFSD)
      scale was constructed. Data were collected via online survey from 131
      predominantly Hispanic college males; scale items were selected by exploratory
      factor analysis. Three moderately strongly correlated factors emerged, though
      they overlapped strongly and are currently considered only for future study. An 8
      item short form of the BFSD scale (the BFSD-S) was created, as well. The full
      BFSD scale showed strong internal consistency and significant correlations with
      gender role attitudes, unequal/coercive relationship attitudes, history of
      misperceiving women's platonic interest as sexual, history of sexual frustration
      in relationships, adult attachment, belief in immanent justice, attitudes toward
      intimate partner violence, and rape myth acceptance. Patterns of divergent
      correlations with other measures also supported the scale's validity. The BFSD-S
      performed nearly identically to the BFSD. Limitations, future directions, and
      implications are discussed. 

PMID- 24920001
TI  - Mental health and bullying in the United States among children aged 6 to 17
      years.
AB  - This article examines the association between mental health disorders and being
      identified as a bully among children between the ages of 6 and 17 years. Data
      from the 2007 National Survey of Children's Health were examined. A total of
      63,997 children had data for both parental reported mental health and bullying
      status. Bivariate analysis and logistic regression was performed to assess the
      association between mental health status and being identified as a bully with an
      age-stratified analysis and sub-analysis by type of mental health disorder. In
      2007, 15.2% of U.S. children ages 6 to 17 years were identified as bullies by
      their parent or guardian. Children with a diagnosis of depression, anxiety, or
      depression had a threefold increased odds of being a bully. The diagnosis of
      depression is associated with a 3.31 increased odds (95% CI = [2.7, 4.07]) of
      being identified as a bully. Children with anxiety and attention deficit and
      hyperactivity disorder (ADHD) had similar odds. The diagnosis of a mental health
      disorder is strongly associated with being identified as a bully. In particular,
      depression, anxiety, and ADHD are strongly associated with being identified as a
      bully. These findings emphasize the importance of providing psychological support
      to not only victims of bullying but bullies as well. Understanding the risk
      profile of childhood bullies is essential in gaining a better grasp of this
      public health problem and in creating useful and appropriate resources and
      interventions to decrease bullying. 

PMID- 24920002
TI  - Validating the virtual string task with the gap test.
AB  - Relational concepts-such as connectedness-may be easy for human adults to
      appreciate; but, obtaining evidence of other species' understanding of
      connectedness has been challenging. One key test of connectedness involves an
      organism's responding to variants of the string task. Using a virtual string
      task, we gave pigeons a pair of strings from which to choose: one connected to a
      full dish of food and a second disconnected from another full dish of food. Our
      pigeons did not at first choose the connected string under conditions of non
      differential reinforcement; later, the birds rapidly learned to choose the
      connected string under conditions of differential reinforcement. Our results
      replicate prior findings with real strings and food dishes, thereby demonstrating
      that pigeons can appreciate the connectedness between a string tether and a dish
      of food, and attesting to the utility and fidelity of the virtual string task. 

PMID- 24920003
TI  - Do children with primary complex motor stereotypies only have movement problems?

PMID- 24920004
TI  - Expression profiling of the wheat pathogen Zymoseptoria tritici reveals genomic
      patterns of transcription and host-specific regulatory programs.
AB  - Host specialization by pathogens requires a repertoire of virulence factors as
      well as fine-tuned regulation of gene expression. The fungal wheat pathogen
      Zymoseptoria tritici (synonym Mycosphaerella graminicola) is a powerful model
      system for the discovery of genetic elements that underlie virulence and host
      specialization. We transcriptionally profiled the early stages of Z. tritici
      infection of a compatible host (wheat) and a noncompatible host (Brachypodium
      distachyon). The results revealed infection regulatory programs common to both
      hosts and genes with striking wheat-specific expression, with many of the latter
      showing sequence signatures of positive selection along the Z. tritici lineage.
      Genes specifically regulated during infection of wheat populated two large
      clusters of coregulated genes that may represent candidate pathogenicity islands.
      On evolutionarily labile, repeat-rich accessory chromosomes (ACs), we identified
      hundreds of highly expressed genes with signatures of evolutionary constraint and
      putative biological function. Phylogenetic analyses suggested that gene
      duplication events on these ACs were rare and largely preceded the
      diversification of Zymoseptoria species. Together, our data highlight the likely
      relevance for fungal growth and virulence of hundreds of Z. tritici genes,
      deepening the annotation and functional inference of the genes of this model
      pathogen. 

PMID- 24920006
TI  - Use of a rat basophil leukemia (RBL) cell-based immunological assay for allergen
      identification, clinical diagnosis of allergy, and identification of anti-allergy
      agents for use in immunotherapy.
AB  - Food allergy is an important public health problem that affects an estimated 8%
      of young children and 2% of adults. With an increasing interest in genetically
      engineered foods, there is a growing need for development of sensitive and
      specific tests to evaluate potential allergenicity of foods and novel proteins as
      well as to determine allergic responses to ensure consumer safety. This review
      covers progress made in the field of development of cell models, specifically
      that involving a rat basophil leukemia (RBL) cell-based immunoassay, for use in
      allergen identification, diagnosis, and immunotherapy. The RBL assay has been
      extensively employed for determining biologically relevant cross-reactivities of
      food proteins, assessing the effect of processing on the allergenicity of food
      proteins, diagnosing allergic responses to whole-food products, and identifying
      anti-allergy food compounds. From the review of the literature, one might
      conclude the RBL cell-based assay is a better test system when compared to wild
      type mast cell and basophil model systems for use in allergen identification,
      diagnosis, and analyses of potential immunotherapeutics. However, it is important
      to emphasize that this assay will only be able to identify those allergens to
      which the human has already been exposed, but will not identify a truly novel
      allergen, i.e. one that has never been encountered as in its preferred
      (humanized) configuration.

PMID- 24920005
TI  - Deciphering the genetic blueprint behind Holstein milk proteins and production.
AB  - Holstein is known to provide higher milk yields than most other cattle breeds,
      and the dominant position of Holstein today is the result of various selection
      pressures. Holstein cattle have undergone intensive selection for milk production
      in recent decades, which has left genome-wide footprints of domestication. To
      further characterize the bovine genome, we performed whole-genome resequencing
      analysis of 10 Holstein and 11 Hanwoo cattle to identify regions containing genes
      as outliers in Holstein, including CSN1S1, CSN2, CSN3, and KIT whose products are
      likely involved in the yield and proteins of milk and their distinctive black-and
      white markings. In addition, genes indicative of positive selection were
      associated with cardiovascular disease, which is related to simultaneous
      propagation of genetic defects, also known as inbreeding depression in Holstein. 

PMID- 24920007
TI  - Pheromone 3kPZS evokes context-dependent serotonin sexual dimorphism in the brain
      of the sea lamprey (Petromyzon marinus).
AB  - Mature male sea lampreys (Petromyzon marinus) release a sex pheromone, 3-keto
      petromyzonol sulfate (3kPZS), that induces sexually dimorphic behavioral
      responses in conspecifics. However, the neural mechanism of such responses is
      mostly unknown. We examined the neurotransmitter serotonin (5-hydroxytryptamine,
      5-HT) and the expression of 5-HT1A receptors in the forebrain and brainstem of
      sea lamprey exposed to the vehicle (0.91 ppm methanol) or 10(-10) M 3kPZS for 2 h
      using high performance liquid chromatography-electrospray ionization tandem mass
      spectrometry, immunohistochemistry and real-time quantitative polymerase chain
      reaction. Exposure to 3kPZS for 2 h increased 5-HT concentration in the forebrain
      of adult females, whereas 5-HT was not detected in the forebrain of adult males.
      On the contrary, 3kPZS exposure decreased 5-HT concentration in the brainstem of
      adult females and had no effect in adult males. Pheromone exposure evoked context
      dependent sexual dimorphism in brain 5-HT1A receptor immunoreactivity, but had no
      effect on 5-HT1A mRNA concentrations in the brain with 2 h exposure time. It
      appears that in sea lamprey pheromone 3kPZS affects the 5-HT system in the brain
      in a context-dependent, sexually dimorphic manner. 

PMID- 24920008
TI  - Time-dependent density functional theory for ion diffusion in electrochemical
      systems.
AB  - We introduce a generic form of time-dependent density functional theory (TDDFT)
      to describe ion diffusion in electrochemical systems to account for steric
      effects and electrostatic correlations neglected in the Poisson-Nernst-Planck
      equations. An efficient numerical algorithm is proposed to analyze the charging
      kinetics of electric double layers in model electrochemical systems that consist
      of spherical ions in a dielectric continuum confined between two planar
      electrodes. By comparing the theoretical predictions from TDDFT and conventional
      electrokinetic methods for constant-voltage charging of the model electrochemical
      cells, we demonstrate that thermodynamic non-ideality plays a pivotal role in
      electrodiffusion even at relatively low electrolyte concentrations, and this
      effect cannot be captured by the lattice-gas model for the excluded volume
      effects. In particular, TDDFT predicts 'wave-like' variation of the ionic density
      profiles that has not been identified in previous investigations. At conditions
      where there are no significant correlations between electric double layers from
      opposite electrodes, the charging kinetics follows an exponential behavior with a
      linear dependence of the relaxation time on the cell thickness in excellent
      agreement with the equivalent circuit model. However, the conventional
      electrokinetic model breaks down when the electrodes are at small separation, in
      particular for systems with low ionic strength or high charging voltage. We also
      find that ionic screening retards the charging kinetics at low salt
      concentrations, but has the opposite effect at large salt concentrations. 

PMID- 24920009
TI  - The influence of personal communities on the self-management of medication
      taking: A wider exploration of medicine work.
AB  - OBJECTIVES: There is a lack of focus on the broader social context, networks and
      influences on medicine-taking as part of illness work. This work adopts a social
      network approach and seeks to explicate the nature of medicine-taking work that
      people with multiple long-term conditions (LTCs) and their social network members
      (SNMs) do in attempting to take their medications on a daily basis, the division
      of labour amongst these members and when and why SNMs become involved in that
      work. METHODS: Semi-structured interviews were conducted with 20 people who had
      multiple LTCs. Medication networks were constructed and the division of labour in
      relation to medication-work was explored. RESULTS: Four types of medication-work
      emerged: medication articulation, surveillance, emotional and informational.
      Involvement of SNMs in medication-work was selective, performed primarily by
      family members, within the home. Involvement reflected network composition and/or
      an individual's conceptualisation/presentation of self. DISCUSSION: Our findings
      support and extend the conceptualisation of routine medicine-taking as a type of
      work. Furthermore, we illustrate the involvement of SNMs in aspects of medicine
      work. Health professionals should explore and support the role of SNMs in
      medicine-taking where possible. Future research should explore the implications
      of network types and compositions on medicine-taking and associated work.

PMID- 24920010
TI  - Disassociation of verbal learning and hippocampal volume in type 2 diabetes and
      major depression.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      verbal learning and memory performance and hippocampal volume in subjects with co
      morbid type 2 diabetes and major depression compared with healthy control
      subjects and subjects with type 2 diabetes alone. METHODS: Twenty four subjects
      with type 2 diabetes and 20 subjects with type 2 diabetes and major depression
      were recruited from endocrinology clinics and were compared with 32 healthy
      control subjects recruited from the community. Subjects were scanned on a 1.5 T
      GE scanner, and hippocampal volumes were measured using Freesurfer. The
      California Verbal Learning Test assessed learning and memory. Significant
      predictors of verbal learning performance (e.g., age, gender, education, blood
      pressure, stroke risk, hemoglobin A1c, and hippocampal volume) were determined
      using a stepwise linear regression. RESULTS: Subjects with diabetes and
      depression had significantly worse performance on verbal list learning compared
      with healthy control subjects. Hippocampal volume was a strong predictor of
      performance in healthy control subjects, and age and hippocampal volume were
      strong predictors in subjects with type 2 diabetes alone. Age alone was a
      significant predictor of verbal learning performance in subjects with diabetes
      and depression. CONCLUSIONS: The relationship between hippocampal volume and
      performance on the California Verbal Learning Test is decoupled in subjects with
      type 2 diabetes and major depression and this decoupling may contribute to poor
      verbal learning and memory performance in this study population.

PMID- 24920011
TI  - Increased MU-opioid receptor expression in metastatic lung cancer.
AB  - BACKGROUND: We and others have previously demonstrated that the MU-opioid
      receptor (MOR) is overexpressed in several human malignancies. There is a seven
      fold increase in MOR in cell lines of human lung cancer. In animal models,
      overexpression of MOR promotes tumour growth and metastasis. We, therefore,
      examined whether MOR expression is increased in metastatic lung cancer. METHODS:
      In this study, we examined the association between MOR expression and metastasis
      in archived biopsy samples from patients with lung cancer. Paraffin-embedded
      patient material was stained using MOR antibody and scored qualitatively by two
      independent pathologists using a four-point scale. RESULTS: In human lung cancer
      and normal adjacent lung samples obtained from 34 lung cancer patients, MOR
      expression was increased significantly in cancer samples from patients with lung
      cancer compared with adjacent control tissue (P=0.0242). When the samples from
      patients with metastatic lung cancer were separated from the cohort of the total
      number of patients with lung cancer, we observed an approximately two-fold
      increase in MOR expression (P=0.0013). CONCLUSIONS: The association between the
      expression of MOR and the progression of the tumour is consistent with the
      hypothesis of a direct effect of MOR on cancer progression.

PMID- 24920012
TI  - Fragmented QRS predicts the arrhythmic events in patients with heart failure
      undergoing ICD implantation for primary prophylaxis: more fragments more
      appropriate ICD shocks.
AB  - BACKGROUND: Fragmented QRS complex (fQRS) is associated with cardiovascular
      outcomes in various patient populations. Although there were clinical studies
      investigating the association of fQRS with arrhythmic events in patients with
      systolic heart failure, the results were conflicting regarding the association of
      implantable cardioverter defibrillator (ICD) shocks and fQRS. In this study, we
      aimed to evaluate the association between the presence and extent of fQRS with
      appropriate ICD shocks and/or all-cause mortality. METHODS: A total of 215
      patients (age: 58.2 +/- 11.6 years, 72.5 % male) with the diagnosis of left
      ventricular systolic heart failure in whom ICD had been implanted for primary
      prophylaxis were enrolled. Standard ECG evaluation revealed fQRS complex in 123
      patients (57.2 %). The phenomenon of fQRS was defined as deflections at the
      beginning of the QRS complex, on top of the R wave, or in the nadir of the S wave
      similar to the definition in CAD. RESULTS: At mean 23.5 +/- 12.1 months follow
      up, all-cause mortality was observed in 45 (20.9 %) patients and 111 (51.6 %)
      patients experienced appropriate ICD shocks. Median number of ECG leads with fQRS
      were higher in patients with appropriate ICD shocks (3 [2-6] vs 1 [0-2], P <
      0.001, respectively). The presence of fQRS (HR: 6.64, 95 % CI: 3.54-12.4, P <
      0.001) and the number of leads with fQRS (HR: 1.35, 95% CI: 1.22-1.67) were found
      as independent predictors of appropriate ICD shocks. Additionally, there was a
      negative correlation between left ventricular ejection fraction and the number of
      leads with fQRS (r = -0.434, P < 0.001). Rates of all-cause mortality did not
      differ between the fQRS(+) (29 [24 % ]) and fQRS(-) (16 [17 % ]) groups (P =
      0.27). CONCLUSION: Our findings suggest that the presence and extent of fQRS
      complex on standard 12-lead ECG predicts appropriate ICD shocks in patients with
      left ventricular systolic heart failure who underwent ICD implantation for
      primary prophylaxis.

PMID- 24920013
TI  - Variable post-zygotic isolation in Drosophila melanogaster/D. simulans hybrids.
AB  - The study of hybrid inviability reveals cryptic divergence between the genetic
      interactions that maintain stable phenotypes in the pure species. We
      characterized the effects of natural variation on the penetrance of hybrid
      inviability phenotypes in crosses between Drosophila melanogaster and two species
      of the D. simulans subcomplex, D. simulans and D. sechellia. Using a panel of
      wild-caught lines, we studied the levels of genetic variance present in D.
      simulans and D. sechellia affecting prezygotic and post-zygotic isolation in
      hybridizations with D. melanogaster females. We observed extensive variability in
      the viability of hybrid individuals, dependent on the genotype of the parents,
      suggesting that intraspecific natural variation manifests directly in hybrid
      phenotypes. Furthermore, we found that genetic background significantly affects
      the penetrance of a well-studied determinant of hybrid inviability: the
      interaction between Hmrmel-Lhrsim. Our results suggest that hybrid inviability-
      and reproductive isolation generally--can be modified by polymorphisms at
      multiple loci segregating within the parental species. Just as the penetrance of
      most mutant phenotypes can be modified by the genetic background within the pure
      species, the penetrance of hybrid inviability phenotypes is highly influenced by
      the parental genotypes.

PMID- 24920015
TI  - Multimodality imaging of cor triatriatum sinister in an octagenerian.
AB  - Cor triatriatum sinister (CTS) is a rare congenital cardiac anomaly in which a
      fibromuscular membrane divides the atrium into two chambers. As CTS can occur as
      an isolated anomaly, it is frequently associated with other cardiac anomalies.
      Although symptoms are usually encountered in infancy, CTS may rarely present in
      adulthood when the membrane contains large fenestration or other escape drainage
      exists. We herein, present an 82-year-old patient with a typical late diagnosis
      of asymptomatic CTS. 

PMID- 24920014
TI  - A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel
      susceptibility locus.
AB  - Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have
      identified associations with genetic variation at both HLA and non-HLA loci;
      however, much of heritable HL susceptibility remains unexplained. Here we perform
      a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed
      by replication in an independent set of 1,281 cases and 3,218 controls to find
      novel risk loci. We identify a novel variant at 19p13.3 associated with HL
      (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86,
      P(combined) = 3.5 * 10(-10)), located in intron 2 of TCF3 (also known as E2A), a
      regulator of B- and T-cell lineage commitment known to be involved in HL
      pathogenesis. This meta-analysis also notes associations between previously
      published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude
      that our data suggest a link between the 19p13.3 locus, including TCF3, and HL
      risk.

PMID- 24920016
TI  - Analysis of laboratory testing results collected in an enhanced chlamydia
      surveillance system in Australia, 2008-2010.
AB  - BACKGROUND: Chlamydial infection is the most common notifiable disease in
      Australia, Europe and the US. Australian notifications of chlamydia rose four
      fold from 20,274 cases in 2002 to 80,846 cases in 2011; the majority of cases
      were among young people aged less than 29 years. Along with test positivity
      rates, an understanding of the number of tests performed and the demographics of
      individuals being tested are key epidemiological indicators. The ACCESS
      Laboratory Network was established in 2008 to address this issue. METHODS: The
      ACCESS Laboratory Network collected chlamydia testing data from 15 laboratories
      around Australia over a three-year period using data extraction software. All
      chlamydia testing data from participating laboratories were extracted from the
      laboratory information system; patient identifiers converted to a unique, non
      reversible code and de-identified data sent to a single database. Analysis of
      data by anatomical site included all specimens, but in age and sex specific
      analysis, only one testing episode was counted. RESULTS: From 2008 to 2010 a
      total of 628,295 chlamydia tests were referred to the 15 laboratories. Of the
      592,626 individual episodes presenting for testing, 70% were from female and 30%
      from male patients. In female patients, chlamydia positivity rate was 6.4%
      overall; the highest rate in 14 year olds (14.3%). In male patients, the
      chlamydia positivity rate was 9.4% overall; the highest in 19 year olds (16.5%).
      The most common sample type was urine (57%). In 3.2% of testing episodes,
      multiple anatomical sites were sampled. Urethral swabs gave the highest
      positivity rate for all anatomical sites in both female (7.7%) and male patients
      (14%), followed by urine (7.6% and 9.4%, respectively) and eye (6.3% and 7.9%,
      respectively). CONCLUSIONS: The ACCESS Laboratory Network data are unique in both
      number and scope and are representative of chlamydia testing in both general
      practice and high-risk clinics. The findings from these data highlight much lower
      levels of testing in young people aged 20 years or less; in particular female
      patients aged less than 16 years, despite being the group with the highest
      positivity rate. Strategies are needed to increase the uptake of testing in this
      high-risk group.

PMID- 24920017
TI  - Quantifying the signals contained in heterogeneous neural responses and
      determining their relationships with task performance.
AB  - The responses of high-level neurons tend to be mixtures of many different types
      of signals. While this diversity is thought to allow for flexible neural
      processing, it presents a challenge for understanding how neural responses relate
      to task performance and to neural computation. To address these challenges, we
      have developed a new method to parse the responses of individual neurons into
      weighted sums of intuitive signal components. Our method computes the weights by
      projecting a neuron's responses onto a predefined orthonormal basis. Once
      determined, these weights can be combined into measures of signal modulation;
      however, in their raw form these signal modulation measures are biased by noise.
      Here we introduce and evaluate two methods for correcting this bias, and we
      report that an analytically derived approach produces performance that is robust
      and superior to a bootstrap procedure. Using neural data recorded from
      inferotemporal cortex and perirhinal cortex as monkeys performed a delayed-match
      to-sample target search task, we demonstrate how the method can be used to
      quantify the amounts of task-relevant signals in heterogeneous neural
      populations. We also demonstrate how these intuitive quantifications of signal
      modulation can be related to single-neuron measures of task performance (d'). 

PMID- 24920018
TI  - Changes in motoneuron afterhyperpolarization duration in stroke survivors.
AB  - Hemispheric brain injury resulting from a stroke is often accompanied by muscle
      weakness in limbs contralateral to the lesion. In the present study, we
      investigated whether weakness in contralesional hand muscle in stroke survivors
      is partially attributable to alterations in motor unit activation, including
      alterations in firing rate modulation range. The afterhyperpolarization (AHP)
      potential of a motoneuron is a primary determinant of motoneuron firing rate. We
      examined differences in AHP duration in motoneurons innervating paretic and less
      impaired (contralateral) limb muscles of hemiparetic stroke survivors as well as
      in control subjects. A novel surface EMG (sEMG) electrode was used to record
      motor units from the first dorsal interosseous muscle. The sEMG data were
      subsequently decomposed to derive single-motor unit events, which were then
      utilized to produce interval (ISI) histograms of the motoneuron discharges. A
      modified version of interval death rate (IDR) analysis was used to estimate AHP
      duration. Results from data analyses performed on both arms of 11 stroke subjects
      and in 7 age-matched control subjects suggest that AHP duration is significantly
      longer for motor units innervating paretic muscle compared with units in
      contralateral muscles and in units of intact subjects. These results were
      supported by a coefficient of variation (CV) analysis showing that paretic motor
      unit discharges have a lower CV than either contralateral or control units. This
      study suggests that after stroke biophysical changes occur at the motoneuron
      level, potentially contributing to lower firing rates and potentially leading to
      less efficient force production in paretic muscles. 

PMID- 24920019
TI  - Basal forebrain dynamics during a tactile discrimination task.
AB  - The nucleus basalis (NB) is a cholinergic neuromodulatory structure that projects
      liberally to the entire cortical mantle and regulates information processing in
      all cortical layers. Here, we recorded activity from populations of single units
      in the NB as rats performed a whisker-dependent tactile discrimination task. Over
      80% of neurons responded with significant modulation in at least one phase of the
      task. Such activity started before stimulus onset and continued for seconds after
      reward delivery. Firing rates monotonically increased with reward magnitude
      during the task, suggesting that NB neurons are not indicating the absolute
      deviation from expected reward amounts. Individual neurons also encoded
      significant amounts of information about stimulus identity. Such robust coding
      was not present when the same stimuli were delivered to lightly anesthetized
      animals, suggesting that the NB neurons contain a sensorimotor, rather than
      purely sensory or motor, representation of the environment. Overall, these
      results support the hypothesis that neurons in the NB provide a value-laden
      representation of the sensorimotor state of the animal as it engages in
      significant behavioral tasks. 

PMID- 24920020
TI  - One night of partial sleep deprivation affects habituation of hypothalamus and
      skin conductance responses.
AB  - Sleep disturbances are prevalent in clinical anxiety, but it remains unclear
      whether they are cause and/or consequence of this condition. Fear conditioning
      constitutes a valid laboratory model for the acquisition of normal and
      pathological anxiety. To explore the relationship between disturbed sleep and
      anxiety in more detail, the present study evaluated the effect of partial sleep
      deprivation (SD) on fear conditioning in healthy individuals. The neural
      correlates of 1) nonassociative learning and physiological processing and 2)
      associative learning (differential fear conditioning) were addressed.
      Measurements entailed simultaneous functional MRI, EEG, skin conductance response
      (SCR), and pulse recordings. Regarding nonassociative learning, partial SD
      resulted in a generalized failure to habituate during fear conditioning, as
      evidenced by reduced habituation of SCR and hypothalamus responses to all
      stimuli. Furthermore, SCR and hypothalamus activity were correlated, supporting
      their functional relationship. Regarding associative learning, effects of partial
      SD on the acquisition of conditioned fear were weaker and did not reach
      statistical significance. The hypothalamus plays an integral role in the
      regulation of sleep and autonomic arousal. Thus sleep disturbances may play a
      causal role in the development of normal and possibly pathological fear by
      increasing the susceptibility of the sympathetic nervous system to stressful
      experiences. 

PMID- 24920022
TI  - Higher neuronal discharge rate in the motor area of the subthalamic nucleus of
      Parkinsonian patients.
AB  - In Parkinson's disease, pathological synchronous oscillations divide the
      subthalamic nucleus (STN) of patients into a dorsolateral oscillatory region and
      ventromedial nonoscillatory region. This bipartite division reflects the motor
      vs. the nonmotor (associative/limbic) subthalamic areas, respectively. However,
      significant topographic differences in the neuronal discharge rate between these
      two STN subregions in Parkinsonian patients is still controversial. In this
      study, 119 STN microelectrode trajectories (STN length > 2 mm, mean = 5.32 mm)
      with discernible oscillatory and nonoscillatory regions were carried on 60
      patients undergoing deep brain stimulation surgery for Parkinson's disease. 2,137
      and 2,152 multiunit stable signals were recorded (recording duration > 10 s, mean
      = 21.25 s) within the oscillatory and nonoscillatory STN regions, respectively.
      Spike detection and sorting were applied offline on every multiunit stable signal
      using an automatic method with systematic quantification of the isolation quality
      (range = 0-1) of the identified units. In all, 3,094 and 3,130 units were
      identified in the oscillatory and nonoscillatory regions, respectively. On
      average, the discharge rate of better-isolated neurons (isolation score > 0.70)
      was higher in the oscillatory region than the nonoscillatory region (44.55 +/-
      0.87 vs. 39.97 +/- 0.77 spikes/s, N = 665 and 761, respectively). The discharge
      rate of the STN neurons was positively correlated to the strength of their own
      and their surrounding 13- to 30-Hz beta oscillatory activity. Therefore, in the
      Parkinsonian STN, beta oscillations and higher neuronal discharge rate are
      correlated and coexist in the motor area of the STN compared with its
      associative/limbic area. 

PMID- 24920021
TI  - A high-density, high-channel count, multiplexed MUECoG array for auditory-cortex
      recordings.
AB  - Our understanding of the large-scale population dynamics of neural activity is
      limited, in part, by our inability to record simultaneously from large regions of
      the cortex. Here, we validated the use of a large-scale active microelectrode
      array that simultaneously records 196 multiplexed micro-electrocortigraphical
      (MUECoG) signals from the cortical surface at a very high density (1,600
      electrodes/cm(2)). We compared MUECoG measurements in auditory cortex using a
      custom "active" electrode array to those recorded using a conventional "passive"
      MUECoG array. Both of these array responses were also compared with data recorded
      via intrinsic optical imaging, which is a standard methodology for recording
      sound-evoked cortical activity. Custom active MUECoG arrays generated more
      veridical representations of the tonotopic organization of the auditory cortex
      than current commercially available passive MUECoG arrays. Furthermore, the
      cortical representation could be measured efficiently with the active arrays,
      requiring as little as 13.5 s of neural data acquisition. Next, we generated
      spectrotemporal receptive fields from the recorded neural activity on the active
      MUECoG array and identified functional organizational principles comparable to
      those observed using intrinsic metabolic imaging and single-neuron recordings.
      This new electrode array technology has the potential for large-scale, temporally
      precise monitoring and mapping of the cortex, without the use of invasive
      penetrating electrodes. 

PMID- 24920024
TI  - Temporal response properties of koniocellular (blue-on and blue-off) cells in
      marmoset lateral geniculate nucleus.
AB  - Visual perception requires integrating signals arriving at different times from
      parallel visual streams. For example, signals carried on the phasic-magnocellular
      (MC) pathway reach the cerebral cortex pathways some tens of milliseconds before
      signals traveling on the tonic-parvocellular (PC) pathway. Visual latencies of
      cells in the koniocellular (KC) pathway have not been specifically studied in
      simian primates. Here we compared MC and PC cells to "blue-on" (BON) and "blue
      off" (BOF) KC cells; these cells carry visual signals originating in short
      wavelength-sensitive (S) cones. We made extracellular recordings in the lateral
      geniculate nucleus (LGN) of anesthetized marmosets. We found that BON visual
      latencies are 10-20 ms longer than those of PC or MC cells. A small number of
      recorded BOF cells (n = 7) had latencies 10-20 ms longer than those of BON cells.
      Within all cell groups, latencies of foveal receptive fields (<10 degrees 
      eccentricity) were longer (by 3-8 ms) than latencies of peripheral receptive
      fields (>10 degrees ). Latencies of yellow-off inputs to BON cells lagged the
      blue-on inputs by up to 30 ms, but no differences in visual latency were seen on
      comparing marmosets expressing dichromatic ("red-green color-blind") or
      trichromatic color vision phenotype. We conclude that S-cone signals leaving the
      LGN on KC pathways are delayed with respect to signals traveling on PC and MC
      pathways. Cortical circuits serving color vision must therefore integrate across
      delays in (red-green) chromatic signals carried by PC cells and (blue-yellow)
      signals carried by KC cells. 

PMID- 24920023
TI  - Enhanced attentional gain as a mechanism for generalized perceptual learning in
      human visual cortex.
AB  - Learning to better discriminate a specific visual feature (i.e., a specific
      orientation in a specific region of space) has been associated with plasticity in
      early visual areas (sensory modulation) and with improvements in the transmission
      of sensory information from early visual areas to downstream sensorimotor and
      decision regions (enhanced readout). However, in many real-world scenarios that
      require perceptual expertise, observers need to efficiently process numerous
      exemplars from a broad stimulus class as opposed to just a single stimulus
      feature. Some previous data suggest that perceptual learning leads to highly
      specific neural modulations that support the discrimination of specific trained
      features. However, the extent to which perceptual learning acts to improve the
      discriminability of a broad class of stimuli via the modulation of sensory
      responses in human visual cortex remains largely unknown. Here, we used
      functional MRI and a multivariate analysis method to reconstruct orientation
      selective response profiles based on activation patterns in the early visual
      cortex before and after subjects learned to discriminate small offsets in a set
      of grating stimuli that were rendered in one of nine possible orientations.
      Behavioral performance improved across 10 training sessions, and there was a
      training-related increase in the amplitude of orientation-selective response
      profiles in V1, V2, and V3 when orientation was task relevant compared with when
      it was task irrelevant. These results suggest that generalized perceptual
      learning can lead to modified responses in the early visual cortex in a manner
      that is suitable for supporting improved discriminability of stimuli drawn from a
      large set of exemplars. 

PMID- 24920026
TI  - Ocular tracking responses to background motion gated by feature-based attention.
AB  - Involuntary ocular tracking responses to background motion offer a window on the
      dynamics of motion computations. In contrast to spatial attention, we know little
      about the role of feature-based attention in determining this ocular response. To
      probe feature-based effects of background motion on involuntary eye movements, we
      presented human observers with a balanced background perturbation. Two clouds of
      dots moved in opposite vertical directions while observers tracked a target
      moving in horizontal direction. Additionally, they had to discriminate a change
      in the direction of motion (+/-10 degrees  from vertical) of one of the clouds. A
      vertical ocular following response occurred in response to the motion of the
      attended cloud. When motion selection was based on motion direction and color of
      the dots, the peak velocity of the tracking response was 30% of the tracking
      response elicited in a single task with only one direction of background motion.
      In two other experiments, we tested the effect of the perturbation when motion
      selection was based on color, by having motion direction vary unpredictably, or
      on motion direction alone. Although the gain of pursuit in the horizontal
      direction was significantly reduced in all experiments, indicating a trade-off
      between perceptual and oculomotor tasks, ocular responses to perturbations were
      only observed when selection was based on both motion direction and color. It
      appears that selection by motion direction can only be effective for driving
      ocular tracking when the relevant elements can be segregated before motion onset.

PMID- 24920025
TI  - Vibration of the organ of Corti within the cochlear apex in mice.
AB  - The tonotopic map of the mammalian cochlea is commonly thought to be determined
      by the passive mechanical properties of the basilar membrane. The other tissues
      and cells that make up the organ of Corti also have passive mechanical
      properties; however, their roles are less well understood. In addition, active
      forces produced by outer hair cells (OHCs) enhance the vibration of the basilar
      membrane, termed cochlear amplification. Here, we studied how these biomechanical
      components interact using optical coherence tomography, which permits vibratory
      measurements within tissue. We measured not only classical basilar membrane
      tuning curves, but also vibratory responses from the rest of the organ of Corti
      within the mouse cochlear apex in vivo. As expected, basilar membrane tuning was
      sharp in live mice and broad in dead mice. Interestingly, the vibratory response
      of the region lateral to the OHCs, the "lateral compartment," demonstrated
      frequency-dependent phase differences relative to the basilar membrane. This was
      sharply tuned in both live and dead mice. We then measured basilar membrane and
      lateral compartment vibration in transgenic mice with targeted alterations in
      cochlear mechanics. Prestin(499/499), Prestin(-/-), and Tecta(C1509G/C1509G) mice
      demonstrated no cochlear amplification but maintained the lateral compartment
      phase difference. In contrast, Sfswap(Tg/Tg) mice maintained cochlear
      amplification but did not demonstrate the lateral compartment phase difference.
      These data indicate that the organ of Corti has complex micromechanical vibratory
      characteristics, with passive, yet sharply tuned, vibratory characteristics
      associated with the supporting cells. These characteristics may tune OHC force
      generation to produce the sharp frequency selectivity of mammalian hearing. 

PMID- 24920027
TI  - Absence of synergy for monosynaptic Group I inputs between abdominal and internal
      intercostal motoneurons.
AB  - Internal intercostal and abdominal motoneurons are strongly coactivated during
      expiration. We investigated whether that synergy was paralleled by synergistic
      Group I reflex excitation. Intracellular recordings were made from motoneurons of
      the internal intercostal nerve of T8 in anesthetized cats, and the specificity of
      the monosynaptic connections from afferents in each of the two main branches of
      this nerve was investigated. Motoneurons were shown by antidromic excitation to
      innervate three muscle groups: external abdominal oblique [EO; innervated by the
      lateral branch (Lat)], the region of the internal intercostal muscle proximal to
      the branch point (IIm), and muscles innervated from the distal remainder (Dist).
      Strong specificity was observed, only 2 of 54 motoneurons showing excitatory
      postsynaptic potentials (EPSPs) from both Lat and Dist. No EO motoneurons showed
      an EPSP from Dist, and no IIm motoneurons showed one from Lat. Expiratory Dist
      motoneurons fell into two groups. Those with Dist EPSPs and none from Lat (group
      A) were assumed to innervate distal internal intercostal muscle. Those with Lat
      EPSPs (group B) were assumed to innervate abdominal muscle (transversus abdominis
      or rectus abdominis). Inspiratory Dist motoneurons (assumed to innervate
      interchondral muscle) showed Dist EPSPs. Stimulation of dorsal ramus nerves gave
      EPSPs in 12 instances, 9 being in group B Dist motoneurons. The complete absence
      of heteronymous monosynaptic Group I reflex excitation between muscles that are
      synergistically activated in expiration leads us to conclude that such
      connections from muscle spindle afferents of the thoracic nerves have little role
      in controlling expiratory movements but, where present, support other motor acts.

PMID- 24920028
TI  - Pulsed infrared radiation excites cultured neonatal spiral and vestibular
      ganglion neurons by modulating mitochondrial calcium cycling.
AB  - Cochlear implants are currently the most effective solution for profound
      sensorineural hearing loss, and vestibular prostheses are under development to
      treat bilateral vestibulopathies. Electrical current spread in these
      neuroprostheses limits channel independence and, in some cases, may impair their
      performance. In comparison, optical stimuli that are spatially confined may
      result in a significant functional improvement. Pulsed infrared radiation (IR)
      has previously been shown to elicit responses in neurons. This study analyzes the
      response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR
      (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded
      consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched
      the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ~637
      mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)]
      variations in the media did not alter the IR-evoked transients, ruling out
      extracellular Ca(2+) involvement or primary mediation by thermal effects on the
      plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane
      channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+)
      cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked
      [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was
      dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These
      results suggest that IR modulation of intracellular calcium cycling contributes
      to stimulation of spiral and vestibular ganglion neurons. As a whole, the results
      suggest selective excitation of neurons in the IR beam path and the potential of
      IR stimulation in future auditory and vestibular prostheses. 

PMID- 24920029
TI  - EEG mean frequency changes in healthy subjects during prefrontal transcranial
      direct current stimulation.
AB  - In this pilot study we evaluated electroencephalographic (EEG) mean frequency
      changes induced by prefrontal transcranial direct current stimulation (tDCS) and
      investigated whether they depended on tDCS electrode montage. Eight healthy
      volunteers underwent tDCS for 15 min during EEG recording. They completed six
      tDCS sessions, 1 wk apart, testing left and right direct current (DC) dipole
      directions with six different montages: four unipolar montages (one electrode on
      a prefrontal area, the other on the opposite wrist) and two bipolar montages
      (both electrodes on prefrontal areas), and a single sham session. EEG power
      spectra were assessed from four 1-min EEG epochs, before, during, and after tDCS.
      During tDCS the outcome variable, brain rate (fb), changed significantly, and the
      changes persisted for minutes after tDCS ended. With the DC dipole directed to
      the left (anode on the left prefrontal area or wrist), fb increased, and with the
      DC dipole directed to the right (anode on the right prefrontal area or wrist), fb
      decreased, suggesting asymmetric prefrontal cortex functional organization in the
      normal human brain. Anodal and cathodal effects were opposite but equally large.
      Gender left these effects unchanged. 

PMID- 24920031
TI  - Anodal transcranial direct current stimulation of the motor cortex induces
      opposite modulation of reciprocal inhibition in wrist extensor and flexor.
AB  - Transcranial direct current stimulation (tDCS) is used as a noninvasive tool to
      modulate brain excitability in humans. Recently, several studies have
      demonstrated that tDCS applied over the motor cortex also modulates spinal neural
      network excitability and therefore can be used to explore the corticospinal
      control acting on spinal neurons. Previously, we showed that reciprocal
      inhibition directed to wrist flexor motoneurons is enhanced during contralateral
      anodal tDCS, but it is likely that the corticospinal control acting on spinal
      networks controlling wrist flexors and extensors is not similar. The primary aim
      of the study was to explore the effects of anodal tDCS on reciprocal inhibition
      directed to wrist extensor motoneurons. To further examine the supraspinal
      control acting on the reciprocal inhibition between wrist flexors and extensors,
      we also explored the effects of the tDCS applied to the ipsilateral hand motor
      area. In healthy volunteers, we tested the effects induced by sham and anodal
      tDCS on reciprocal inhibition pathways innervating wrist muscles. Reciprocal
      inhibition directed from flexor to extensor muscles and the reverse situation,
      i.e., reciprocal inhibition, directed from extensors to flexors were studied in
      parallel with the H reflex technique. Our main finding was that contralateral
      anodal tDCS induces opposing effects on reciprocal inhibition: it decreases
      reciprocal inhibition directed from flexors to extensors, but it increases
      reciprocal inhibition directed from extensors to flexors. The functional result
      of these opposite effects on reciprocal inhibition seems to favor wrist extension
      excitability, suggesting an asymmetric descending control onto the interneurons
      that mediate reciprocal inhibition. 

PMID- 24920030
TI  - Rapid acquisition of novel interface control by small ensembles of arbitrarily
      selected primary motor cortex neurons.
AB  - Pioneering studies demonstrated that novel degrees of freedom could be controlled
      individually by directly encoding the firing rate of single motor cortex neurons,
      without regard to each neuron's role in controlling movement of the native limb.
      In contrast, recent brain-computer interface work has emphasized decoding outputs
      from large ensembles that include substantially more neurons than the number of
      degrees of freedom being controlled. To bridge the gap between direct encoding by
      single neurons and decoding output from large ensembles, we studied monkeys
      controlling one degree of freedom by comodulating up to four arbitrarily selected
      motor cortex neurons. Performance typically exceeded random quite early in single
      sessions and then continued to improve to different degrees in different
      sessions. We therefore examined factors that might affect performance.
      Performance improved with larger ensembles. In contrast, other factors that might
      have reflected preexisting synaptic architecture-such as the similarity of
      preferred directions-had little if any effect on performance. Patterns of
      comodulation among ensemble neurons became more consistent across trials as
      performance improved over single sessions. Compared with the ensemble neurons,
      other simultaneously recorded neurons showed less modulation. Patterns of
      voluntarily comodulated firing among small numbers of arbitrarily selected
      primary motor cortex (M1) neurons thus can be found and improved rapidly, with
      little constraint based on the normal relationships of the individual neurons to
      native limb movement. This rapid flexibility in relationships among M1 neurons
      may in part underlie our ability to learn new movements and improve motor skill. 

PMID- 24920032
TI  - Two interconnected kernels of reciprocally inhibitory interneurons underlie
      alternating left-right swim motor pattern generation in the mollusk Melibe
      leonina.
AB  - The central pattern generator (CPG) underlying the rhythmic swimming behavior of
      the nudibranch Melibe leonina (Mollusca, Gastropoda, Heterobranchia) has been
      described as a simple half-center oscillator consisting of two reciprocally
      inhibitory pairs of interneurons called swim interneuron 1 (Si1) and swim
      interneuron 2 (Si2). In this study, we identified two additional pairs of
      interneurons that are part of the swim CPG: swim interneuron 3 (Si3) and swim
      interneuron 4 (Si4). The somata of Si3 and Si4 were both located in the pedal
      ganglion, near that of Si2, and both had axons that projected through the pedal
      commissure to the contralateral pedal ganglion. These neurons fulfilled the
      criteria for inclusion as members of the swim CPG: 1) they fired at a fixed phase
      in relation to Si1 and Si2, 2) brief changes in their activity reset the motor
      pattern, 3) prolonged changes in their activity altered the periodicity of the
      motor pattern, 4) they had monosynaptic connections with each other and with Si1
      and Si2, and 5) their synaptic actions helped explain the phasing of the motor
      pattern. The results of this study show that the motor pattern has more complex
      internal dynamics than a simple left/right alternation of firing; the CPG circuit
      appears to be composed of two kernels of reciprocally inhibitory neurons, one
      consisting of Si1, Si2, and the contralateral Si4 and the other consisting of
      Si3. These two kernels interact with each other to produce a stable rhythmic
      motor pattern. 

PMID- 24920033
TI  - A review of the effects of nuts on appetite, food intake, metabolism, and body
      weight.
AB  - Tree nuts and peanuts are good sources of many nutrients and antioxidants, but
      they are also energy dense. The latter often limits intake because of concerns
      about their possible contribution to positive energy balance. However, evidence
      to date suggests that nuts are not associated with predicted weight gain. This is
      largely due to their high satiety value, leading to strong compensatory dietary
      responses, inefficiency in absorption of the energy they contain, a possible
      increment in resting energy expenditure, and an augmentation of fat oxidation.
      Preliminary evidence suggests that these properties are especially evident when
      they are consumed as snacks. 

PMID- 24920034
TI  - Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the
      European Prospective Investigation into Cancer and Nutrition (EPIC).
AB  - Fruit, vegetables, and certain components of plant foods, such as fiber, have
      long been thought to protect against cancer. The European Prospective
      Investigation into Cancer and Nutrition (EPIC) is a prospective cohort that
      includes >500,000 participants from 10 European countries and has made a
      substantial contribution to knowledge in this research area. The purpose of this
      article is to summarize the findings published thus far from the EPIC study on
      the associations between fruit, vegetable, or fiber consumption and the risk of
      cancer at 14 different sites. The risk of cancers of the upper gastrointestinal
      tract was inversely associated with fruit intake but was not associated with
      vegetable intake. The risk of colorectal cancer was inversely associated with
      intakes of total fruit and vegetables and total fiber, and the risk of liver
      cancer was also inversely associated with the intake of total fiber. The risk of
      cancer of the lung was inversely associated with fruit intake but was not
      associated with vegetable intake; this association with fruit intake was
      restricted to smokers and might be influenced by residual confounding due to
      smoking. There was a borderline inverse association of fiber intake with breast
      cancer risk. For the other 9 cancer sites studied (stomach, biliary tract,
      pancreas, cervix, endometrium, prostate, kidney, bladder, and lymphoma) there
      were no reported significant associations of risk with intakes of total fruit,
      vegetables, or fiber. 

PMID- 24920035
TI  - Preface to the Sixth International Congress on Vegetarian Nutrition.

PMID- 24920036
TI  - Activation of peroxisome proliferator activator receptor delta in mouse impacts
      lipid composition and placental development at early stage of gestation.
AB  - Peroxisome proliferator-activated receptor delta (Ppard) activation has been
      implicated in regulating a multitude of biological processes in placental
      development. In this study, we employed the UPLC-ESI-TOFMS approach to
      investigate the metabolic traits in placenta from GW501516-treated mice at
      Embryonic Day 10.5. By analyzing the mass spectrum data, ions with the most
      significant differences between control and GW501516-treated groups were
      identified. Among these metabolites, the fatty acids, phospholipids, and sterol
      lipids were dramatically increased. Ingenuity Pathway Analysis (IPA) showed that
      phosphatidylethanolamine biosynthesis and glycolysis were the top two altered
      metabolic pathways involved in carbohydrate metabolism, energy production, and
      lipid metabolism. Subsequent immunoblotting experiments provided evidence for
      positive correlation of PPARD level and AKT and ERK signaling pathways upon
      GW501516 treatment. Furthermore, the stimulation of GW501516 increased
      trophoblast cell fusion gene syncytin-A (Syna), but not syncytin-B (Synb),
      expression, suggesting a potential role of Ppard activation in promoting
      cytotrophoblast differentiation. Our results reveal that Ppard activation elicits
      dramatic changes of the metabolic activities in placenta, which is correlated to
      AKT and ERK signaling. 

PMID- 24920037
TI  - Hyperplastic obesity and liver steatosis as long-term consequences of suboptimal
      in vitro culture of mouse embryos.
AB  - In the present study, we identify and describe an obese phenotype in mice as a
      long-term consequence of a suboptimal in vitro culture that resulted from the
      addition of fetal calf serum (FCS) into the culture medium. Mice produced with
      FCS displayed a high mortality rate (approximately 55% versus 15% in control mice
      within 20 mo) and increased sensitivity to the development of obesity in
      adulthood when fed either a standard or a high-fat diet. These mice developed
      hyperplastic obesity that was characterized by a significant expansion of the fat
      pads (approximately 25% and 32% higher body weight in male and female mice over
      controls, respectively) with unchanged adipocyte size. We observed a sexual
      dimorphism in the development of obesity in the mice produced with FCS. Whereas
      the female mice displayed hypertension, hyperleptinemia, and fatty liver, the
      male mice only displayed glucose intolerance. The mRNA expression of
      metabolically relevant genes in the adipose tissue was also affected. The males
      produced with FCS expressed higher mRNA levels of the genes that activate fatty
      acid oxidation (peroxisome proliferator-activated receptor alpha [Ppara,
      PPARalpha] and acyl-CoA oxidase 1 [Acox1, ACOX1]) and thermogenesis (uncoupling
      protein 1 [Ucp1, UCP1]), which may counteract the metabolic phenotype.
      Conversely, the females produced with FCS generally expressed lower levels of
      these metabolic genes. In the females, the obese phenotype was associated with
      inhibition of the lipogenic pathway (peroxisome proliferator-activated receptor
      gamma [Pparg, PPARgamma] and fatty acid synthase [Fasn, FAS]), indicating a
      saturation of the storage capacity of the adipose tissue. Overall, our data
      indicate that the exposure to suboptimal in vitro culture conditions can lead to
      the sexually dimorphic development of obesity in adulthood. 

PMID- 24920039
TI  - Juvenile ovary to testis transition in zebrafish involves inhibition of ptges.
AB  - The sex differentiation mechanisms in zebrafish (Danio rerio) remains elusive,
      partly because of the absence of sex chromosomes but also because the process
      appears to depend on the synchrony of multiple genes and possibly environmental
      factors. Zebrafish gonadal development is initiated through the development of
      immature oocytes. Depending on multiple signaling cues, in about half of the
      individuals, the juvenile ovaries degenerate or undergo apoptosis to initiate
      testes development while the other half maintains the oogenic pathway. We have
      previously shown that activation of NFkappaB and prostaglandin synthase 2 (ptgs2)
      results in female-biased sex ratios. Prostaglandin synthase and prostaglandins
      are involved in multiple physiological functions, including cell survival and
      apoptosis. In the present study, we show that inhibition of ptgs2 by meloxicam
      results in male-biased sex ratios. On further evaluation, we observed that
      exposure with the prostaglandin D2 (PGD2) analogue BW-245C induced SRY-box
      containing gene 9a (sox9a) and resulted in male-biased sex ratios. On the other
      hand, prostaglandin E2 (PGE2) treatment resulted in female-biased sex ratios and
      involved activation of NFkappaB and the beta-catenin pathway as well as
      inhibition of sox9. Exposure to the beta-catenin inhibitor PNU-74654 resulted in
      up-regulation of ptgds and male-biased sex ratios, further confirming the
      involvement of beta-catenin in the female differentiation pathway. In this study,
      we show that PGD2 and PGE2 can program the gonads to either the testis or the
      ovary differentiation pathways, indicating that prostaglandins are involved in
      the regulation of zebrafish gonadal differentiation. 

PMID- 24920038
TI  - Ovarian membrane-type matrix metalloproteinases: induction of MMP14 and MMP16
      during the periovulatory period in the rat, macaque, and human.
AB  - An intrafollicular increase in proteolytic activity drives ovulatory events.
      Surprisingly, the periovulatory expression profile of the membrane-type matrix
      metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has
      not been extensively examined. Expression profiles of the MT-MMPs were
      investigated in ovarian tissue from well-characterized rat and macaque
      periovulatory models and naturally cycling women across the periovulatory period.
      Among the six known MT-MMPs, mRNA expression of Mmp14, Mmp16, and Mmp25 was
      increased after human chorionic gonadotropin (hCG) administration in rats. In
      human granulosa cells, mRNA expression of MMP14 and MMP16 increased following hCG
      treatment. In contrast, mRNA levels of MMP16 and MMP25 in human theca cells were
      unchanged before ovulation but declined by the postovulatory stage. In macaque
      granulosa cells, hCG increased mRNA for MMP16 but not MMP14. Immunoblotting
      showed that protein levels of MMP14 and MMP16 in rats increased, similar to their
      mRNA expression. In macaque granulosa cells, only the active form of the MMP14
      protein increased after hCG, unlike its mRNA or the proprotein. By
      immunohistochemistry, both MMP14 and MMP16 localized to the different ovarian
      cell types in rats and humans. Treatment with hCG resulted in intense
      immunoreactivity of MMP14 and MMP16 proteins in the granulosa and theca cells.
      The present study shows that MMP14 and MMP16 are increased by hCG administration
      in the ovulating follicle, demonstrating that these MMPs are conserved among
      rats, macaques, and humans. These findings suggest that MT-MMPs could have an
      important role in promoting ovulation and remodeling of the ovulated follicle
      into the corpus luteum. 

PMID- 24920040
TI  - Possible role of p38 MAPK-MNK1-EMI2 cascade in metaphase-II arrest of mouse
      oocytes.
AB  - The Mos-MAPK signaling pathway involving the Mos-MEK1/2-ERK1/2-RSK1/2/3 or MSK1
      EMI2 cascade is directly linked to metaphase-II arrest of vertebrate oocytes. In
      this study, we examined whether p38, a member of the MAPK subfamily, is regulated
      under the control of Mos and contributes to metaphase-II arrest in the mouse
      oocyte. Morpholino oligonucleotide-mediated depletion of Mos revealed a
      remarkable decrease in phosphorylation of p38. Simultaneous treatment of oocytes
      with two chemical inhibitors of p38 and MEK1/2 induced both release from
      metaphase II and degradation of cyclin B1, whereas the treatment with each of
      these two inhibitors had little effect. Moreover, phosphorylation of EMI2 was
      dramatically abolished by addition of the two inhibitors. Indeed, MNK1, a kinase
      downstream of p38, exhibited the ability to phosphorylate EMI2. These results
      suggest that in addition to the Mos-MEK1/2 pathway, the Mos-mediated p38 pathway
      may be implicated in metaphase-II arrest. 

PMID- 24920041
TI  - Higher brain extracellular potassium is associated with brain metabolic distress
      and poor outcome after aneurysmal subarachnoid hemorrhage.
AB  - INTRODUCTION: Elevated brain potassium levels ([K+]) are associated with neuronal
      damage in experimental models. The role of brain extracellular [K+] in patients
      with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) and its association
      with hemorrhage load, metabolic dysfunction and outcome has not been studied so
      far. METHODS: Cerebral microdialysis (CMD) samples from 28 poor grade aSAH
      patients were analyzed for CMD [K+] for 12 consecutive days after ictus, and time
      matched to brain metabolic and hemodynamic parameters as well as corresponding
      plasma [K+]. Statistical analysis was performed using a generalized estimating
      equation with an autoregressive function to handle repeated observations of an
      individual patient. RESULTS: CMD [K+] did not correlate with plasma [K+]
      (Spearman's rho = 0.114, P = 0.109). Higher CMD [K+] was associated with the
      presence of intracerebral hematoma on admission head computed tomography, CMD
      lactate/pyruvate ratio >40 and CMD lactate >4 mmol/L (P < 0.05). In vitro
      retrodialysis data suggest that high CMD [K+] was of brain cellular origin.
      Higher CMD [K+] was significantly associated with poor 3-month outcome, even
      after adjusting for age and disease severity (P < 0.01). CONCLUSIONS: The results
      of this pilot study suggest that brain extracellular [K+] may serve as a
      biomarker for brain tissue injury in poor-grade aSAH patients. Further studies
      are needed to elucidate the relevance of brain interstitial K+ levels in the
      pathophysiology of secondary brain injury after aSAH.

PMID- 24920043
TI  - Synthesis of lucifensin by native chemical ligation and characteristics of its
      isomer having different disulfide bridge pattern.
AB  - The antimicrobial 40-amino-acid-peptide lucifensin was synthesized by native
      chemical ligation (NCL) using N-acylbenzimidazolinone (Nbz) as a linker group.
      NCL is a method in which a peptide bond between two discreet peptide chains is
      created. This method has been applied to the synthesis of long peptides and
      proteins when solid-phase synthesis is imcompatible. Two models of ligation were
      developed: [15+25] Ala-Cys and [19+21] His-Cys. The [19+21] His-Cys method gives
      lower yield because of the lower stability of 18-peptide-His-Nbz-CONH2 peptide,
      as suggested by density functional theory calculation. Acetamidomethyl
      deprotection and subsequent oxidation of the ligated linear lucifensin gave a
      mixture of lucifensin isomers, which differed in the location of their disulfide
      bridges only. The dominant isomer showed unnatural pairing of cysteines [C1-6],
      [C3-5], and [C2-4], which limits its ability to form alpha-helical structure. The
      activity of isomeric lucifensin toward Bacillus subtilis, Staphylococcus aureus,
      and Micrococcus luteus was lower than that of the natural lucifensin. The desired
      product native lucifensin was prepared from this isomer using a one-pot reduction
      with dithiotreitol and subsequent air oxidation in slightly alkaline medium.

PMID- 24920042
TI  - Development of oral osteomucosal tissue constructs in vitro and localization of
      fluorescently-labeled bisphosphonates to hard and soft tissue.
AB  - Bisphosphonates (BPs) are anti-resorptive agents commonly used to treat bone
      related diseases; however, soft tissue-related side-effects are frequently
      reported in some BP users, such as oral or gastrointestinal (GI) ulcerations. BPs
      are stable analogs of pyrophosphate and have high affinity to hydroxyapatite,
      allowing them to bind to the bone surfaces and exert suppressive effects on
      osteoclast functions. However, the underlying mechanisms as to how bone-seeking
      BPs also exert cytotoxic effects on soft tissue remain unknown. In the present
      study, we investigated the localization of nitrogen-containing BPs (N-BPs) in
      hard and soft tissue using fluorescently-labeled N-BPs in vitro. We developed
      osteomucosal tissue constructs in vitro to recapitulate the hard and soft tissue
      of the oral cavity. A histological examination of the osteomucosal tissue
      constructs revealed a differentiated epithelium over the bone containing
      osteocytes and the periosteum, similar to that observed in the rat palatal
      tissues. Following treatment with the fluorescently-labeled bisphosphonate, AF647
      ZOL, the osteomucosal constructs exhibited fluorescent signals, not only in the
      bone, but also in the epithelium. No fluorescent signals were observed from the
      control- or ZOL-treated constructs, as expected. Collectively, the data from the
      present study suggest that N-BPs localize to epithelial tissue and that such a
      localization and subsequent toxicity of N-BPs may be associated, at least in
      part, with soft tissue-related side-effects.

PMID- 24920044
TI  - Among infants at hereditary risk for type 1 diabetes, the introduction of solid
      foods before or after 4-5 months of age is associated with increased diabetes
      risk.

PMID- 24920045
TI  - Major contribution of the Ehrlich pathway for 2-phenylethanol/rose flavor
      production in Ashbya gossypii.
AB  - Aroma alcohols of fermented food and beverages are derived from fungal amino
      acids catabolism via the Ehrlich pathway. This linear pathway consists of three
      enzymatic reactions to form fusel alcohols. Regulation of some of the enzymes
      occurs on the transcriptional level via Aro80. The riboflavin overproducer Ashbya
      gossypii produces strong fruity flavours in contrast to its much less aromatic
      relative Eremothecium cymbalariae. Genome comparisons indicated that A. gossypii
      harbors genes for aromatic amino acid catabolism (ARO8a, ARO8b, ARO10, and ARO80)
      while E. cymbalariae only encodes ARO8a and thus lacks major components of
      aromatic amino acid catabolism. Volatile compound (VOC) analysis showed that both
      Eremothecium species produce large amounts of isoamyl alcohol while A. gossypii
      also produces high levels of 2-phenylethanol. Deletion of the A. gossypii ARO
      genes did not confer any growth deficiencies. However, A. gossypii ARO-mutants
      (except Agaro8a) were strongly impaired in aroma production, particularly in the
      production of the rose flavour 2-phenylethanol. Conversely, overexpression of
      ARO80 via the AgTEF1 promoter resulted in 50% increase in VOC production.
      Together these data indicate that A. gossypii is a very potent flavour producer
      and that amongst the non-Saccharomyces biodiversity strains can be identified
      that could provide positive sensory properties to fermented beverages. 

PMID- 24920046
TI  - Home based telemedicine intervention for patients with uncontrolled hypertension-
      a real life non-randomized study.
AB  - BACKGROUND: Control of blood pressure is frequently inadequate in spite of
      availability of several classes of well tolerated and effective antihypertensive
      drugs. Several factors, including the use of suboptimal doses of drugs,
      inadequate or ineffective treatments and poor drug compliance may be the reason
      for this phenomenon. The aim of the current non- randomized study was to evaluate
      the effectiveness of a Home-Based Telemedicine service in patients with
      uncontrolled hypertension. METHODS: 74 patients were enrolled in a Home Based
      Telemedicine group and 94 patients in the Usual Care group. At baseline and at
      the end of the study, patients in both groups were seen in a cardiology office.
      Patients in Home Based Telemedicine group additionally were followed by a
      physician-nurse, through scheduled and unscheduled telephone appointments. These
      patients also received a blood pressure measuring device that could transmit the
      readings to a central data monitor via secure data connection. RESULTS: During
      the study period (80 +/- 25 days), a total of 17401 blood pressure measurements
      were taken in the Home Based Telemedicine group corresponding to 236 +/- 136
      readings per patient and a mean daily measurement of 3 +/- 1.7. The scheduled
      telephone contacts (initiated by the nurse) equaled to 5.2 +/- 4.3/patient (370
      in total) and the unscheduled telephone contacts (initiated by the patients) were
      0.4 +/- 0.9/patient (30 in total). The mean systolic blood pressure values
      decreased from 153 +/- 19 mmHg to 130 +/- 15 mmHg (p < 0.0001) at the end of the
      study and diastolic blood pressure values decreased from 89 +/- 10 mmHg to 76 +/-
      11 mmHg (p < 0.0001). In the Usual Care group, the mean systolic blood pressure
      values decreased from 156 +/- 16 mmHg to 149 +/- 17 mmHg (p < 0.05) at the end of
      the study and diastolic blood pressure values decreased from 90 +/- 8 mmHg to 86
      +/- 9 mmHg (p < 0.05). The changes in drug therapy initiated following telephone
      contacts were 1.81 +/- 1.73 per patient. CONCLUSIONS: The addition of a
      structured physician-nurse approach supported by remote telemonitoring of blood
      pressure is likely to improve outcome in patients with uncontrolled hypertension.

PMID- 24920047
TI  - Planktonic or non-planktonic food in young-of-the-year European perch Perca
      fluviatilis in ponds.
AB  - Higher biomass especially of some aquatic macrophyte species offered a higher
      density of phytophilous zoobenthos, but did not increase the proportion of non
      planktonic to planktonic prey in young-of-the-year perch Perca fluviatilis. Both
      abundance and biomass of non-planktonic prey dominated over planktonic prey in
      the pond with lower biomass of aquatic macrophytes and lower food. Survival of P.
      fluviatilis was lower (20%) in the pond with lower food than in the other pond
      (34%), however, specific growth rate (1.3% day(-1) ) and final Fulton's condition
      factor of P. fluviatilis were similar in both ponds.

PMID- 24920048
TI  - How does a novel monoplanar pedicle screw perform biomechanically relative to
      monoaxial and polyaxial designs?
AB  - BACKGROUND: Minimally invasive spinal fusions frequently require placement of
      pedicle screws through small incisions with limited visualization. Polyaxial
      pedicle screws are favored due to the difficulty of rod insertion with fixed
      monoaxial screws. Recently, a novel monoplanar screw became available that is
      mobile in the coronal plane to ease rod insertion but fixed in the sagittal plane
      to eliminate head slippage during flexion loads; however, the strength of this
      screw has not been established relative to other available screw designs.
      QUESTIONS/PURPOSES: We compared the static and dynamic load to failure in
      polyaxial, monoaxial, and monoplanar pedicle screws. METHODS: Six different
      manufacturers' screws (42 total) were tested in three categories (polyaxial, n =
      4; monoaxial, n = 1; monopolar, n = 1) utilizing titanium rods. An additional
      test was performed using cobalt-chromium rods with the monopolar screws only.
      Screws were embedded into polyethylene blocks and rods were attached using the
      manufacturers' specifications. Static and dynamic testing was performed. Dynamic
      testing began at 80% of static yield strength at 1 Hz for 50,000 cycles. RESULTS:
      In static testing, monoaxial and monoplanar screws sustained higher loads than
      all polyaxial screw designs (range, 37%-425% higher; p < 0.001). The polyaxial
      screws failed at the head-screw interface, while the monoaxial and monoplanar
      screws failed by rod breakage in the static test. The dynamic loads to failure
      were greater with the monoplanar and monoaxial screws than with the polyaxial
      screws (range, 35%-560% higher; p < 0.001). With dynamic testing, polyaxial
      screws failed via screw-head slippage between 40% and 95% of static yield
      strength, while failures in monoaxial and monoplanar screws resulted from either
      screw shaft or rod breakage. CONCLUSIONS: All polyaxial screws failed at the
      screw-head interface in static and dynamic testing and at lower values than
      monoaxial/monoplanar screw designs. Monoplanar and monoaxial screws failed at
      forces well above expected in vivo values; this was not the case for most
      polyaxial screws. CLINICAL RELEVANCE: Polyaxial screw heads slip on the screw
      shank at lower values than monoaxial or monoplanar screws, and this results in
      angular change between the rod and pedicle screw, which could cause loss of
      segmental lordosis. The novel monoplanar screw used in this study may combine
      ease of rod placement with sagittal plane strength.

PMID- 24920049
TI  - Dynamic mitochondrial changes during differentiation of P19 embryonic carcinoma
      cells into cardiomyocytes.
AB  - Murine P19 embryonal carcinoma cells are multipotent cells that can differentiate
      into cardiomyocytes when treated with dimethyl sulfoxide. This experimental model
      provides an invaluable tool to study different aspects of cardiac
      differentiation, such as the function of cardiac-specific transcription factors
      and signaling pathways, and the regulation of contractile protein expression. The
      role of mitochondria during cardiac differentiation is unclear. In this context,
      we have examined the mitochondrial-related changes in undifferentiated and
      differentiated P19 cells. We observed that mitochondrial DNA content sharply
      decreased in P19 cell aggregates compared to undifferentiated cells, accompanied
      by decreased levels of adenosine triphosphate (ATP) and reactive oxygen species
      (ROS). Following the aggregation stage, the mitochondrial DNA content reached its
      highest level on day 7 of the differentiation process, with the intracellular ROS
      level showing a trend to increase, similar to cellular ATP production. In
      conclusion, our study on differentiating P19 embryonal carcinoma cells provides
      new insights into the role of mitochondria in the differentiation of P19 stem
      cells into beating cardiomyocytes. 

PMID- 24920050
TI  - Improved synthetic route to methyl 1-fluoroindan-1-carboxylate (FICA Me ester)
      and 4-methyl derivatives.
AB  - An improved synthetic route has been developed for the preparation of methyl 1
      fluoroindan-1-carboxylate (FICA Me ester) from 1-indanone. Methyl 4-methyl-1
      fluoroindan-1-carboxylate (4-Me-FICA Me ester) was also prepared following the
      same procedure. 

PMID- 24920051
TI  - Eco-efficient one-pot synthesis of quinazoline-2,4(1H,3H)-diones at room
      temperature in water.
AB  - An efficient one-pot synthesis of quinazoline-2,4(1H,3H)-diones was developed.
      First, the reactions of anthranilic acid derivatives with potassium cyanate
      afforded the corresponding urea derivatives. Then, cyclization of the urea
      derivatives with NaOH afforded the monosodium salts of benzoylene urea. Finally,
      HCl treatment afforded the desired products in near-quantitative yields. This is
      an eco-efficient method because all the reactions were carried out in water, and
      the desired products were obtained simply by filtration. The aqueous filtrate was
      the only waste generated from the reaction. We scaled up the reaction to 1 kg
      starting material, thus establishing an alternative approach for the green
      synthesis of quinazoline-2,4(1H,3H)-diones in the chemical and pharmaceutical
      industries.

PMID- 24920052
TI  - Two novel alleles HLA-DRB1*11:150 and HLA-DRB1*14:145 identified in Saudi
      individuals.
AB  - Two new HLA- DRB1 alleles were identified by sequence-based typing method (SBT)
      in 1100 participants in the Saudi Stem Cell Donor Registry. HLA-DRB1*11:150
      differs from HLA-DRB1*11:01:01G by a single C to A substitution at nucleotide
      position 5580 in exon 2, resulting in an amino acid change from alanine to
      glutamic acid at position 74. HLA-DRB1*14:145 differs from HLA-DRB1*14:04 by a C
      to G substitution at nucleotide position 5511 in exon 2, resulting in an amino
      acid change from threonine to arginine at position 51. 

PMID- 24920053
TI  - Catalytic biorefining of plant biomass to non-pyrolytic lignin bio-oil and
      carbohydrates through hydrogen transfer reactions.
AB  - Through catalytic hydrogen transfer reactions, a new biorefining method results
      in the isolation of depolymerized lignin--a non-pyrolytic lignin bio-oil--in
      addition to pulps that are amenable to enzymatic hydrolysis. Compared with
      organosolv lignin, the lignin bio-oil is highly susceptible to further
      hydrodeoxygenation under low-severity conditions and therefore establishes a
      unique platform for lignin valorization by heterogeneous catalysis. Overall, the
      potential of a catalytic biorefining method designed from the perspective of
      lignin utilization is reported.

PMID- 24920055
TI  - Influence of alkyl chain length and anion species on ionic liquid structure at
      the graphite interface as a function of applied potential.
AB  - Atomic force microscopy (AFM) force measurements elucidate the effect of cation
      alkyl chain length and the anion species on ionic liquid (IL) interfacial
      structure at highly ordered pyrolytic graphite (HOPG) surfaces as a function of
      potential. Three ILs are examined: 1-hexyl-3-methylimidazolium
      tris(pentafluoroethyl)trifluorophosphate ([HMIM] FAP), 1-ethyl-3
      methylimidazolium tris(pentafluoroethyl)trifluorophosphate ([EMIM] FAP), and 1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM] TFSA). The
      step-wise force-distance profiles indicate the ILs adopt a multilayered
      morphology near the surface. When the surface is biased positively or negatively
      versus Pt quasireference electrode, both the number of steps, and the force
      required to rupture each step increase, indicating stronger interfacial
      structure. At all potentials, push-through forces for [HMIM] FAP are the highest,
      because the long alkyl chain results in strong cohesive interactions between
      cations, leading to well-formed layers that resist the AFM tip. The most layers
      are observed for [EMIM] FAP, because the C2 chains are relatively rigid and the
      dimensions of the cation and anion are similar, facilitating neat packing. [EMIM]
      TFSA has the smallest push-through forces and fewest layers, and thus the weakest
      interfacial structure. Surface-tip attractive forces are measured for all ILs. At
      the same potential, the attractions are the strongest for [EMIM] TFSA and the
      weakest for [HMIM] FAP because the interfacial layers are better formed for the
      longer alkyl chain cation. This means interfacial forces are stronger, which
      masks the weak attractive forces. 

PMID- 24920054
TI  - The health-related quality of life of Chinese patients with lower urinary tract
      symptoms in primary care.
AB  - PURPOSE: The aim of this study was to evaluate the health-related quality of life
      (HRQOL) of Chinese primary care patients with lower urinary tract symptoms
      (LUTS). METHODS: Five hundred and nineteen primary care subjects with LUTS
      completed a structured questionnaire containing the International Prostate
      Symptom Score, the adapted Incontinence Impact Questionnaire-7, the International
      Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, the
      Chinese (HK) SF-12 Health Survey Version 2 (SF-12 v2) and the Depression, Anxiety
      and Stress Scale-21. RESULTS: LUTS patients had poorer HRQOL for the General
      Health and the Vitality domains and lower Physical Component Summary scores, but
      better HRQOL for the Role Emotion domain than the adjusted Hong Kong population
      norms. Clinical factors associated with poorer HRQOL measured by the SF-12 v2
      included having more severe LUTS and having more severe depressive, anxiety and
      stress symptoms. Socio-demographic factors associated with poorer SF-12 v2 were
      consistent with those found in the general populations. Clinical and socio
      demographic factors associated with poorer HRQOL assessed by condition-specific
      measures included having more severe LUTS (excluding intermittency and
      straining), the presence of mixed urinary incontinence, having more severe
      anxiety and stress symptoms, younger age, being not married, being in employment
      and having a lower household income. CONCLUSIONS: LUTS had substantial negative
      impact on patients' overall health perception and global well-being in Chinese
      population. A decline in HRQOL might be a key determinant for Chinese patients
      with LUTS to seek treatment. Patients with nocturia, frequency, urgency or mixed
      urinary incontinence and younger patients deserve more treatment attention
      because they appear to have poorer HRQOL.

PMID- 24920059
TI  - Well-defined nano-sunflowers formed by self-assembly of a rod-coil amphiphile in
      water and their morphology transformation based on a water-soluble
      pillar[5]arene.
AB  - Well-defined nano-sunflowers were constructed by self-assembling a rod-coil
      amphiphile in water, and their morphologies transformed by addition of a water
      soluble pillar[5]arene and Ag2O were also investigated. 

PMID- 24920060
TI  - Homo- and heteroleptic alkoxycarbene f-element complexes and their reactivity
      towards acidic N-H and C-H bonds.
AB  - The reactivity of a series of organometallic rare earth and actinide complexes
      with hemilabile NHC-ligands towards substrates with acidic C-H and N-H bonds is
      described. The synthesis, characterisation and X-ray structures of the new
      heteroleptic mono- and bis(NHC) cyclopentadienyl complexes LnCp2(L) 1 (Ln = Sc,
      Y, Ce; L = alkoxy-tethered carbene [OCMe2CH2(1-C{NCHCHN(i)Pr})]), LnCp(L)2 (Ln =
      Y) , and the homoleptic tetrakis(NHC) complex Th(L)4 4 are described. The
      reactivity of these complexes, and of the homoleptic complexes Ln(L)3 (Ln = Sc 3,
      Ce), with E-H substrates is described, where EH = pyrrole C4H4NH, indole C8H6NH,
      diphenylacetone Ph2CC(O)Me, terminal alkynes RC=CH (R = Me3Si, Ph), and
      cyclopentadiene C5H6. Complex 1-Y heterolytically cleaves and adds pyrrole and
      indole N-H across the metal carbene bond, whereas 1-Ce does not, although 3 and 4
      form H-bonded adducts. Complexes 1-Y and 1-Sc form adducts with CpH without
      cleaving the acidic C-H bond, 1-Ce cleaves the Cp-H bond, but 2 reacts to form
      the very rare H(+)-[C5H5](-)-H(+) motif. Complex 1-Ce cleaves alkyne C-H bonds
      but the products rearrange upon formation, while complex 1-Y cleaves the C-H bond
      in diphenylacetone forming a product which rearranges to the Y-O bonded enolate
      product.

PMID- 24920061
TI  - Melatonin and ubiquitin: what's the connection?
AB  - Melatonin has been widely studied for its role in photoperiodism in seasonal
      breeders; it is also a potent antioxidant. Ubiquitin, a protein also widespread
      in living cells, contributes to many cellular events, although the most well
      known is that of tagging proteins for destruction by the proteasome. Herein, we
      suggest a model in which melatonin interacts with the ubiquitin-proteasome system
      to regulate a variety of seemingly unrelated processes. Ubiquitin, for example,
      is a major regulator of central activity of thyroid hormone type 2 deiodinase;
      the subsequent regulation of T3 may be central to the melatonin-induced changes
      in seasonal reproduction and seasonal changes in metabolism. Both melatonin and
      ubiquitin also have important roles in protecting cells from oxidative stress. We
      discuss the interaction of melatonin and the ubiquitin-proteasome system in
      oxidative stress through regulation of the ubiquitin-activating enzyme, E1.
      Previous reports have shown that glutathiolation of this enzyme protects proteins
      from unnecessary degradation. In addition, evidence is discussed concerning the
      interaction of ubiquitin and melatonin in activation of the transcription factor
      NF-kappaB as well as modulating cellular levels of numerous signal transducing
      factors including the tumor suppressor, p53. Some of the actions of melatonin on
      the regulatory particle of the proteasome appear to be related to its inhibition
      of the calcium-dependent calmodulin kinase II, an enzyme which reportedly
      copurifies with proteasomes. Many of the actions of melatonin on signal
      transduction are similar to those of a proteasome inhibitor. While these actions
      of melatonin could be explained by a direct inhibitory action on the catalytic
      core particle of the proteasome, this has not been experimentally verified. If
      our hypothesis of melatonin as a general inhibitor of the ubiquitin-proteasome
      system is confirmed, it is predicted that more examples of this interaction will
      be demonstrated in a variety of tissues in which ubiquitin and melatonin co
      exist. Furthermore, the hypothesis of melatonin as an inhibitor of the ubiquitin
      proteasome system will be a very useful model for clinical testing of melatonin. 

PMID- 24920062
TI  - Mechanical forces induce odontoblastic differentiation of mesenchymal stem cells
      on three-dimensional biomimetic scaffolds.
AB  - The mechanical induction of cell differentiation is well known. However, the
      effect of mechanical compression on odontoblastic differentiation remains to be
      elucidated. Thus, we first determined the optimal conditions for the induction of
      human dental pulp stem cells (hDPSCs) into odontoblastic differentiation in
      response to mechanical compression of three-dimensional (3D) scaffolds with
      dentinal tubule-like pores. The odontoblastic differentiation was evaluated by
      gene expression and confocal laser microscopy. The optimal conditions, which
      were: cell density, 4.0 * 105 cells/cm2 ; compression magnitude, 19.6 kPa; and
      loading time, 9 h, significantly increased expression of the odontoblast-specific
      markers dentine sialophosphoprotein (DSPP) and enamelysin and enhanced the
      elongation of cellular processes into the pores of the membrane, a typical
      morphological feature of odontoblasts. In addition, upregulation of bone
      morphogenetic protein 7 (BMP7) and wingless-type MMTV integration site family
      member 10a (Wnt10a) was observed. Moreover, the phosphorylation levels of mitogen
      activated protein kinases (MAPKs), extracellular signal-regulated kinase 1/2
      (ERK1/2) and p38 were also enhanced by mechanical compression, indicating the
      involvement of the MAPK signalling pathway. It is noteworthy that human
      mesenchymal stem cells (MSCs) derived from bone marrow and amnion also
      differentiated into odontoblasts in response to the optimal mechanical
      compression, demonstrating the importance of the physical structure of the
      scaffold in odontoblastic differentiation. Thus, odontoblastic differentiation of
      hDPSCs is promoted by optimal mechanical compression through the MAPK signalling
      pathway and expression of the BMP7 and Wnt10a genes. The 3D biomimetic scaffolds
      with dentinal tubule-like pores were critical for the odontoblastic
      differentiation of MSCs induced by mechanical compression. Copyright (c) 2014
      John Wiley & Sons, Ltd.

PMID- 24920063
TI  - Acquired initiating mutations in early hematopoietic cells of CLL patients.
AB  - Appropriate cancer care requires a thorough understanding of the natural history
      of the disease, including the cell of origin, the pattern of clonal evolution,
      and the functional consequences of the mutations. Using deep sequencing of flow
      sorted cell populations from patients with chronic lymphocytic leukemia (CLL), we
      established the presence of acquired mutations in multipotent hematopoietic
      progenitors. Mutations affected known lymphoid oncogenes, including BRAF, NOTCH1,
      and SF3B1. NFKBIE and EGR2 mutations were observed at unexpectedly high
      frequencies, 10.7% and 8.3% of 168 advanced-stage patients, respectively. EGR2
      mutations were associated with a shorter time to treatment and poor overall
      survival. Analyses of BRAF and EGR2 mutations suggest that they result in
      deregulation of B-cell receptor (BCR) intracellular signaling. Our data propose
      disruption of hematopoietic and early B-cell differentiation through the
      deregulation of pre-BCR signaling as a phenotypic outcome of CLL mutations and
      show that CLL develops from a pre-leukemic phase. SIGNIFICANCE: The origin and
      pathogenic mechanisms of CLL are not fully understood. The current work indicates
      that CLL develops from pre-leukemic multipotent hematopoietic progenitors
      carrying somatic mutations. It advocates for abnormalities in early B-cell
      differentiation as a phenotypic convergence of the diverse acquired mutations
      observed in CLL.

PMID- 24920064
TI  - Stable acetate production in extreme-thermophilic (70 degrees C) mixed culture
      fermentation by selective enrichment of hydrogenotrophic methanogens.
AB  - The control of metabolite production is difficult in mixed culture fermentation.
      This is particularly related to hydrogen inhibition. In this work,
      hydrogenotrophic methanogens were selectively enriched to reduce the hydrogen
      partial pressure and to realize efficient acetate production in extreme
      thermophilic (70 degrees C) mixed culture fermentation. The continuous stirred
      tank reactor (CSTR) was stable operated during 100 days, in which acetate
      accounted for more than 90% of metabolites in liquid solutions. The yields of
      acetate, methane and biomass in CSTR were 1.5 +/- 0.06, 1.0 +/- 0.13 and 0.4 +/-
      0.05 mol/mol glucose, respectively, close to the theoretical expected values. The
      CSTR effluent was stable and no further conversion occurred when incubated for 14
      days in a batch reactor. In fed-batch experiments, acetate could be produced up
      to 34.4 g/L, significantly higher than observed in common hydrogen producing
      fermentations. Acetate also accounted for more than 90% of soluble products
      formed in these fed-batch fermentations. The microbial community analysis
      revealed hydrogenotrophic methanogens (mainly Methanothermobacter
      thermautotrophicus and Methanobacterium thermoaggregans) as 98% of Archaea,
      confirming that high temperature will select hydrogenotrophic methanogens over
      aceticlastic methanogens effectively. This work demonstrated a potential
      application to effectively produce acetate as a value chemical and methane as an
      energy gas together via mixed culture fermentation.

PMID- 24920066
TI  - One-year changes in bone mineral density and bone turnover markers in
      premenopausal amateur runners: a prospective study.
AB  - A prospective study was conducted to clarify the 1-year changes in lumbar spine
      and hip bone mineral density (BMD) and bone turnover markers in premenopausal
      amateur runners and to determine whether jumping and muscle-strengthening
      exercises have additive effects on the bone parameters in these runners. Thirty
      six premenopausal amateur runners were recruited and were divided into the
      following two groups: a jumping plus muscle-strengthening exercise group (n =21)
      and a control group (n =15). All participants continued their running practice
      for 1 year, and the lumbar spine and total hip BMD and bone turnover markers were
      monitored. For all participants, the lumbar spine and total hip BMD increased
      modestly after 1 year (1.31% and 1.54%, respectively) in addition to increases in
      the bone-specific alkaline phosphatase, osteocalcin, and tartrate-resistant acid
      phosphatase 5b levels (13.2%-27.8%), indicating mild effects of running activity
      on bone turnover and BMD at clinically relevant skeletal sites. Jumping plus
      muscle-strengthening exercises did not significantly influence any bone
      parameters; however, it was difficult to draw definite conclusions because
      compliance was poor. These results suggest that long-distance running at the
      recreational level may be useful in maintaining bone health in premenopausal
      women.

PMID- 24920068
TI  - The remarkable effect of ivabradine in two adolescents with dilated
      cardiomyopathy.

PMID- 24920069
TI  - RAD001 can reverse drug resistance of SGC7901/DDP cells.
AB  - To investigate the role of RAD001 in the reversing of drug resistance of
      SGC7901/DDP, we cultured SGC7901/DDP cells with different groups of drugs
      (RAD001, cisplatin (DDP) alone, or the combination of RAD001 and DDP); after
      that, we detected the drug sensitivity, cell apoptosis, and levels of P-gp, MRP1,
      and survivin in the cells of SGC7901/DDP by MTT (3-(4, 5-dimethylthiazol-2-yl)-2,
      5-diphe-nyltetrazolium bromide) assay, flow cytometry, immunohistochemical
      analysis, and Western blot analysis. There was no significant difference between
      DDP 2.5-mg/L group and negative control group. When the cells were pretreated
      with RAD001 2.5, 5 nmol/L, the proliferation of SGC7901/DDP cells was inhibited
      by DDP 2.5 mg/L significantly, compared to negative control group, DDP 2.5-mg/L
      group, and RAD001 2.5, 5-nmol/L group, respectively (P < 0.05); there were
      significant differences between combination groups (P < 0.05). DDP 2.5 mg/L and
      RAD001 2.5 nmol/L did not induce apoptosis of SGC7901/DDP cells alone (P > 0.05).
      When SGC7901/DDP cells were pretreated with RAD001 2.5 nmol/L, DDP 2.5 mg/L
      increased the apoptosis rate significantly compared to groups of control and DDP
      2.5 mg/L alone (P < 0.05). Immunohistochemical staining (Table 5, Fig. 2) and
      Western blot analysis (Fig. 3) indicated that when SGC7901/DDP cells were
      pretreated with RAD001 2.5 nmol/L, the expression of P-gp, MRP1, and survivin
      decreased by different degrees. Our results have confirmed that RAD001 in
      combination with DDP could overcome chemoresistance of SGC7901/DDP cells by
      decreasing the levels of P-gp, MRP1, and survivin through the mTOR pathway.

PMID- 24920071
TI  - Efficacy and safety of adalimumab in psoriatic patients previously treated with
      etanercept in a real-world setting.
AB  - INTRODUCTION: Knowledge on the efficacy and safety of adalimumab in psoriasis
      patients switching from etanercept is scarce, especially on the influence that
      causes of etanercept discontinuation may have on adalimumab response. OBJECTIVES:
      To evaluate the response, adverse effects and factors that may influence the
      efficacy and safety of adalimumab in psoriasis patients who failed on etanercept
      therapy in a real-world setting. METHODS: Data from all moderate to severe plaque
      psoriasis patients who switched from etanercept to adalimumab were extracted from
      a registry of biological therapies of our department. Primary endpoint was the
      percentage of patients achieving PASI 50 at weeks 12, 24, and 52. Secondary
      endpoints were the percentages of patients achieving PASI 75 and PASI 90,
      patients who maintained PASI values <5 and <3, and the safety of adalimumab.
      RESULTS: Of 35 patients who fulfilled the study criteria, 82.9% achieved PASI 50
      at week 12, 74.3% at week 24, and 74.3% at week 52 on adalimumab treatment.
      Eleven of 16 primary and 11 of 17 secondary nonresponders to etanercept responded
      to adalimumab. There were no treatment discontinuations due to side effects.
      CONCLUSIONS: Previous etanercept failure seems not influence the success and
      safety of adalimumab treatment in moderate to severe plaque psoriasis.

PMID- 24920070
TI  - H19 promotes pancreatic cancer metastasis by derepressing let-7's suppression on
      its target HMGA2-mediated EMT.
AB  - The long noncoding RNA (lncRNA) H19 has been recently characterized as an
      oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal
      adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the
      levels of H19 was overexpressed in PDAC compared with adjacent normal tissues,
      but also H19 expression was upregulated remarkably in primary tumors which
      subsequently metastasized, compared to those did not metastasis. Subsequently,
      the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was
      evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell
      invasion and migration. We further demonstrated that H19 promoted PDAC cell
      invasion and migration at least partially by increasing HMGA2-mediated epithelial
      mesenchymal transition (EMT) through antagonizing let-7. This study suggests an
      important role of H19 in regulating metastasis of PDAC and provides some clues
      for elucidating the lncRNA-miRNA functional network in cancer.

PMID- 24920072
TI  - Gender differences in Afghan drug-abuse treatment: an assessment of treatment
      entry characteristics, dropout, and outcomes.
AB  - OBJECTIVE: The current study examines gender differences in drug-abuse treatment
      (DAT) entry, dropout, and outcomes in seven DAT centers in Afghanistan. This is
      the first study to examine gender differences in DAT programming in Afghanistan.
      DESIGN: A prospective cohort design of 504 women and men in seven DAT centers in
      Afghanistan was used in this study and the analyses examined whether gender
      differences exist for patients (1) at treatment entry, (2) at treatment dropout,
      and (3) for treatment outcomes. RESULTS: Gender differences were found at
      baseline for patient characteristics, drug use, crime, and social and
      occupational functioning. Results showed a trend that women remained in treatment
      longer than men. Looking at gender differences in treatment success, results
      showed greater reductions in drug use and crime, and greater social functioning
      among women. CONCLUSION: Results provide preliminary evidence for potential
      treatment success of women-tailored DAT programming in Afghanistan. Results also
      indicate that DAT appears to be successful among Afghan men; however, lower
      positive outcomes for men when compared to women suggest that more efforts should
      focus on tailoring DAT programming to the specific needs of Afghan men as well.
      Study limitations are addressed, and important policy implications are discussed.

PMID- 24920075
TI  - Viral factors and predicting disease outcomes in chronic hepatitis B.

PMID- 24920076
TI  - Efficient, compassionate, and fractured: contemporary care in the ICU.

PMID- 24920077
TI  - Functional C1q is present in the skin mucus of Siberian sturgeon (Acipenser
      baerii).
AB  - The skin mucus of fish acts as the first line of self-protection against
      pathogens in the aquatic environment and comprises a number of innate immune
      components. However, the presence of the critical classical complement component
      C1q, which links the innate and adaptive immune systems of mammalians, has not
      been explored in a primitive actinopterygian fish. In this study, we report that
      C1q is present in the skin mucus of the Siberian sturgeon (Acipenser baerii). The
      skin mucus was able to inhibit the growth of Escherichia coli. The bacteriostatic
      activity of the skin mucus was reduced by heating and by pre-incubation with EDTA
      or mouse anti-human C1q antibody. We also detected C1q protein in skin mucus
      using the western blot procedure and isolated a cDNA that encodes the Siberian
      sturgeon C1qC, which had 44.7-51.4% identity with C1qCs in teleosts and
      tetrapods. A phylogenetic analysis revealed that Siberian sturgeon C1qC lies at
      the root of the actinopterygian branch and is separate from the tetrapod branch.
      The C1qC transcript was expressed in many tissues as well as in skin. Our data
      indicate that C1q is present in the skin mucus of the Siberian sturgeon to
      protect against water-borne bacteria, and the C1qC found in the sturgeon may
      represent the primitive form of teleost and tetrapod C1qCs. 

PMID- 24920074
TI  - Hyperpolarized gas diffusion MRI for the study of atelectasis and acute
      respiratory distress syndrome.
AB  - Considerable uncertainty remains about the best ventilator strategies for the
      mitigation of atelectasis and associated airspace stretch in patients with acute
      respiratory distress syndrome (ARDS). In addition to several immediate
      physiological effects, atelectasis increases the risk of ventilator-associated
      lung injury, which has been shown to significantly worsen ARDS outcomes. A number
      of lung imaging techniques have made substantial headway in clarifying the
      mechanisms of atelectasis. This paper reviews the contributions of computed
      tomography, positron emission tomography, and conventional MRI to understanding
      this phenomenon. In doing so, it also reveals several important shortcomings
      inherent to each of these approaches. Once these shortcomings have been made
      apparent, we describe how hyperpolarized (HP) gas MRI--a technique that is
      uniquely able to assess responses to mechanical ventilation and lung injury in
      peripheral airspaces--is poised to fill several of these knowledge gaps. The HP
      MRI-derived apparent diffusion coefficient (ADC) quantifies the restriction of
      (3) He diffusion by peripheral airspaces, thereby obtaining pulmonary structural
      information at an extremely small scale. Lastly, this paper reports the results
      of a series of experiments that measured ADC in mechanically ventilated rats in
      order to investigate (i) the effect of atelectasis on ventilated airspaces, (ii)
      the relationship between positive end-expiratory pressure (PEEP), hysteresis, and
      the dimensions of peripheral airspaces, and (iii) the ability of PEEP and
      surfactant to reduce airspace dimensions after lung injury. An increase in ADC
      was found to be a marker of atelectasis-induced overdistension. With recruitment,
      higher airway pressures were shown to reduce stretch rather than worsen it.
      Moving forward, HP MRI has significant potential to shed further light on the
      atelectatic processes that occur during mechanical ventilation.

PMID- 24920078
TI  - Development of cross-resistance by Aspergillus fumigatus to clinical azoles
      following exposure to prochloraz, an agricultural azole.
AB  - BACKGROUND: The purpose of this study was to unveil whether azole antifungals
      used in agriculture, similar to the clinical azoles used in humans, can evoke
      resistance among relevant human pathogens like Aspergillus fumigatus, an
      ubiquitous agent in nature. Additionally, cross-resistance with clinical azoles
      was investigated. Antifungal susceptibility testing of environmental and clinical
      isolates of A. fumigatus was performed according to the CLSI M38-A2 protocol. In
      vitro induction assays were conducted involving daily incubation of susceptible
      A. fumigatus isolates, at 35 degrees C and 180 rpm, in fresh GYEP broth medium
      supplemented with Prochloraz (PCZ), a potent agricultural antifungal, for a
      period of 30 days. Minimal inhibitory concentrations (MIC) of PCZ and clinical
      azoles were monitored every ten days. In order to assess the stability of the
      developed MIC, the strains were afterwards sub-cultured for an additional 30 days
      in the absence of antifungal. Along the in vitro induction process, microscopic
      and macroscopic cultural observations were registered. RESULTS: MIC of PCZ
      increased 256 times after the initial exposure; cross-resistance to all tested
      clinical azoles was observed. The new MIC value of agricultural and of clinical
      azoles maintained stable in the absence of the selective PCZ pressure. PCZ
      exposure was also associated to morphological colony changes: macroscopically the
      colonies became mostly white, losing the typical pigmentation; microscopic
      examination revealed the absence of conidiation. CONCLUSIONS: PCZ exposure
      induced Aspergillus fumigatus morphological changes and an evident increase of
      MIC value to PCZ as well as the development of cross-resistance with
      posaconazole, itraconazole and voriconazole.

PMID- 24920079
TI  - Repeated stereotactic body radiotherapy for oligometastatic prostate cancer
      recurrence.
AB  - PURPOSE: To assess the outcome of prostate cancer (PCa) patients diagnosed with
      oligometastatic disease at recurrence and treated with stereotactic body
      radiotherapy (SBRT). METHODS: Non-castrate patients with up to 3 synchronous
      metastases (bone and/or lymph nodes) diagnosed on positron emission tomography -
      computed tomography, following biochemical recurrence after local curative
      treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions
      or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADT-FS)
      defined as the time interval between the first day of SBRT and the initiation of
      ADT was the primary endpoint. ADT was initiated if more than 3 metastases were
      detected during follow-up even when patients were still asymptomatic. Secondary
      endpoints were local control, progression free survival (PFS) and toxicity.
      Toxicity was scored using the Common Terminology Criteria for Adverse Events.
      RESULTS: With a median follow-up from time of SBRT of 2 years, we treated 50
      patients with 70 metastatic lesions with a local control rate of 100%. The
      primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera
      (2%). The median PFS was 19 mo (95% CI: 13-25 mo) with 75% of recurring patients
      having <=3 metastases. A 2nd and 3rd course of SBRT was delivered in 19 and 6
      patients respectively. This results in a median ADT-FS of 25 months (20-30 mo).
      On univariate analysis, only a short PSA doubling time was a significant
      predictor for both PFS (HR: 0.90, 95% CI: 0.82 - 0.99) and ADT-FS (HR: 0.83; 95%
      CI: 0.71 - 0.97). Ten patients (20%) developed toxicity following treatment,
      which was classified as grade I in 7 and grade II in 3 patients. CONCLUSION:
      Repeated SBRT for oligometastatic prostate cancer postpones palliative androgen
      deprivation therapy with 2 years without grade III toxicity.

PMID- 24920080
TI  - Ca2+ switches the effect of PS-containing membranes on Factor Xa from activating
      to inhibiting: implications for initiation of blood coagulation.
AB  - Calcium (Ca2+) plays a pivotal role in cellular and organismal physiology. The
      Ca2+ ion has an intermediate protein-binding affinity and thus it can serve as an
      on/off switch in the regulation of different biochemical processes. The serum
      level of ionized Ca2+ is regulated with normal ionized Ca2+ being in the range
      1.10-1.3 mM. Hypocalcaemia (free Ca2+<1.1 mM) in critically ill patients is
      commonly accompanied by haemostatic abnormalities, ranging from isolated
      thrombocytopenia to complex defects such as disseminated intravascular
      coagulation, commonly thought to be due to insufficient functioning of
      anticoagulation pathways. A small amount of fXa (Factor Xa) produced by Factor
      VIIa and exposed tissue factor is key to initiating blood coagulation by
      producing enough thrombin to induce the later stages of coagulation. fXa must
      bind to PS (phosphatidylserine)-containing membranes to produce thrombin at a
      physiologically significant rate. In the present study, we show that overall fXa
      activity on PS-containing membranes is sharply regulated by a 'Ca2+ switch'
      centred at 1.16 mM, below which fXa is active and above which fXa forms inactive
      dimers on PS-exposing membranes. Our data lead to a mathematical model that
      predicts the variation of fXa activity as a function of both Ca2+ and membrane
      concentrations. Because the critical Ca2+ concentration is at the lower end of
      the normal plasma ionized Ca2+ concentration range, we propose a new regulatory
      mechanism by which local Ca2+ concentration switches fXa from an intrinsically
      active form to a form requiring its cofactor [fVa (Factor Va)] to achieve
      significant activity. 

PMID- 24920081
TI  - The relationship between changes in quality of life outcomes and progression of
      Alzheimer's disease: results from the dependence in AD in England 2 longitudinal
      study.
AB  - OBJECTIVE: The relationship between conventional indicators of Alzheimer's
      disease (AD) progression and quality of life (QoL) outcomes is unclear.
      Dependence on others has been recommended as a unifying construct in defining AD
      severity. This study examined the relationship between indicators of disease
      severity (including dependence) and changes in QoL and utility over 18 months.
      METHODS: A multi-centre, cohort study was conducted across 18 UK sites. One
      hundred and forty-five patients with possible/probable AD and their caregivers
      completed assessments of disease severity (Dependence Scale, Mini-mental state
      examination, Neuropsychiatric Inventory, Disability Assessment for Dementia),
      dementia-specific QoL (DEMQOL, DEMQOL-Proxy) and generic health-related utility
      (EQ-5D) at both time points. RESULTS: There was evidence of individual change in
      QoL over 18 months, with over 50% of patients reporting either maintenance or
      improvement of life quality. The EQ-5D proxy suggested a mean decline in QoL,
      whereas the DEMQOL-Proxy indicated overall improvement. In the subsample of
      people who self-reported QoL and utility, no mean change was evident. Changes in
      dependence did not explain changes on any QoL or utility outcome. There was a
      weak association between the EQ-5D proxy and changes in cognition, whereas
      changes on the DEMQOL-Proxy were partly explained by changes in behavioural
      disturbance. CONCLUSIONS: The natural progression of AD over 18 months does not
      lead to inevitable decline in QoL or utility. There are no clear or consistent
      direct relationships between changes in disease severity and QoL outcomes. The
      impact of increasing dependence and worsening disease severity is likely buffered
      by a combination of psychological, social and environmental factors.

PMID- 24920083
TI  - Low emotional response to traumatic footage is associated with an absence of
      analogue flashbacks: an individual participant data meta-analysis of 16 trauma
      film paradigm experiments.
AB  - Most people will experience or witness a traumatic event. A common occurrence
      after trauma is the experience of involuntary emotional memories of the traumatic
      event, herewith "flashbacks". Some individuals, however, report no flashbacks.
      Prospective work investigating psychological factors associated with an absence
      of flashbacks is lacking. We performed an individual participant data meta
      analysis on 16 experiments (n = 458) using the trauma film paradigm to
      investigate the association of emotional response to traumatic film footage and
      commonly collected baseline characteristics (trait anxiety, current depression,
      trauma history) with an absence of analogue flashbacks. An absence of analogue
      flashbacks was associated with low emotional response to the traumatic film
      footage and, to a lesser extent, low trait anxiety and low current depression
      levels. Trauma history and recognition memory for the film were not significantly
      associated with an absence of analogue flashbacks. Understanding why some
      individuals report an absence of flashbacks may aid preventative treatments
      against flashback development. 

PMID- 24920082
TI  - Characteristics and experiences of patients with localized prostate cancer who
      left an active surveillance program.
AB  - BACKGROUND: Understanding the experiences of men leaving active surveillance
      programs is critical to making such programs viable for men with localized
      prostate cancer. OBJECTIVE: To generate hypotheses about the factors that
      influence patients' decisions to leave an active surveillance program. METHODS:
      Using data from the Johns Hopkins active surveillance cohort, bivariate analyses
      and multinomial regression models examined characteristics of men who self
      elected to leave, those who stayed in the program, and those who left because of
      disease reclassification. We interviewed patients who self-elected to leave.
      RESULTS: Of 1,159 men in active surveillance, 9 % self-elected to leave. In
      interviews with a sample of 14 men who self-elected to leave, uncertainty
      involved in active surveillance participation, existence of personal criteria
      distinct from providers' clinical criteria-and fear of cancer were important
      factors in decisions to leave. CONCLUSION: Men leaving active surveillance were
      motivated by a number of factors, including patient-defined criteria, which might
      differ from clinical recommendations. To ensure active surveillance
      participation, it may be important to address cancer-related anxiety and personal
      criteria underlying patient decisions.

PMID- 24920085
TI  - Validation of a French version of the pure procrastination scale (PPS).
AB  - Procrastination is a widespread phenomenon that affects everyone's day-to-day
      life and interferes with the clinical treatment of several psychopathological
      states. To assess this construct, Steel (2010) developed the Pure Procrastination
      Scale (PPS), a short scale intended to capture the general notion of
      dysfunctional delay. The aim of the current study was to present a French version
      of this questionnaire. To this end, the 12 items of the PPS were translated into
      French and data were collected from an online survey in a sample of 245 French
      speaking individuals from the general population. The results revealed that one
      item had problematic face validity; it was therefore removed. Exploratory and
      confirmatory analyses performed on the resulting 11-item version of the French
      PPS indicated that the scale was composed of two factors ("voluntary delay" and
      "observed delay") depending on a common, higher-order construct ("general
      procrastination"). Good internal consistency and test-retest reliability were
      found. External validity was supported by specific relationships with measures of
      personality traits, impulsivity, and subjective well-being. The French PPS
      therefore presents satisfactory psychometric properties and may be considered a
      reliable and valid instrument for research, teaching and clinical practice. 

PMID- 24920086
TI  - [Differences in the selenium supply of cattle across Europe].
AB  - OBJECTIVE: Evaluation of differences in the selenium supply of cattle across
      Europe. MATERIAL AND METHODS: A total of 35,722 serum samples from cattle
      throughout Europe (unknown clinical status), which had been sent by veterinarians
      to the IDEXX Vet Med Lab Ludwigsburg, Germany between January 1st, 2006, and June
      30th, 2013, were analyzed routinely for the selenium concentration using ICP
      analysis. RESULTS: The collective data of the selenium concentration in cattle
      serum display seasonal variations, with a lower concentration during summer when
      compared to the winter. In recent years, the selenium supply has decreased. The
      farm size, husbandry conditions, economic situation, soil selenium concentration
      and the countries' specific feeding together play a key role in the selenium
      supply of the herd. Hungary and the Scandinavian countries Sweden and Denmark
      show the best selenium supply in Europe. A very poor situation exists in France
      and Luxembourg (> 50% of the cattle samples are undersupplied). CONCLUSION AND
      CLINICAL RELEVANCE: An optimal selenium supply for cattle is very important; a
      trace element deficiency can cause negative health effects and impair herd
      performance. The selenium concentration varies considerably, depending upon
      feeding and husbandry conditions. Therefore, a serum selenium analysis in cattle
      is essential and should be performed annually.

PMID- 24920087
TI  - Reproductive performance of Arab mares in the Kingdom of Saudi Arabia.
AB  - OBJECTIVE: The aim of this study was to evaluate the reproductive performance of
      the Arab mares in the Kingdom of Saudi Arabia (KSA). METHODS: Managers of 26
      studfarms containing 1014 Arab mares at five districts were asked to complete a
      questionnaire on the reproductive efficiency of their mares. RESULTS: The mean
      age at first mating was 3.06 +/- 0.5 years. Mares were mated equally in winter
      and all over the year. Natural mating was mostly used (76.9%). The means of
      estrus duration and estrus interval were 6.58 +/- 1 days and 19.57 +/- 1.8 days,
      respectively. The means of first service and over- all pregnancy rates and the
      number of cycles/pregnancy were 52.71 +/- 20.2%, 83.72 +/- 15.0%, and 1.46 +/-
      0.3, respectively, with no effect of the postpartum interval, district, or
      season. The average pregnancy duration was 335.5 +/- 10.2 days. It was shorter in
      mares mated by day 9 postpartum than in those mated later (p < 0.05). The ratio
      of stallion/mares ranged from 1:4 to 1:24, with no correlation with the pregnancy
      rates or the number of cycles/pregnancy. DISCUSSION: Photoperiodic regulation and
      changes in the hypothalamic-hypophyseal axis of mares are usually associated with
      the seaso- nal reproductive activity of mares in the temperate but not in
      subtropical areas. Short duration of gestation for mares mated by day 9 after
      foaling may be related to the nutritional status of dams. CONCLUSION: The
      obtained data represent the first record of the reproductive performance of Arab
      mares in the KSA, which could be used to anticipate their performance under
      different managements. CLINICAL RELEVANCE: The Arab mares in the KSA are not
      seasonal and can reproduce efficiently all over the year. District and season did
      not influence the fertility.

PMID- 24920088
TI  - [Breeding management of black rhinos (Diceros bicornis michaeli) in Magdeburg
      Zoo].
AB  - OBJECTIVE: The African black rhino is an endangered species. In Germany there are
      only five zoos where this species is kept and breeding has not been successful in
      all of them. In Magdeburg Zoo the last birth occurred in December 2005, and
      during the following years, no matings could be observed. During the construction
      of a new enclosure to enable a more natural mating behaviour, the reproduction
      status of the rhino cows was evaluated and a hormonal treatment was performed.
      MATERIAL AND METHODS: Since 2009, faecal samples from two rhino cows (Diceros
      bicornis michaeli; "Mana", 30 years old, and "Maleika", 17 years old) were
      collected periodically, and the pregnanediol-glucuronide (PdG) and oestradiol
      concentrations were determined using enzyme immunoassay and radioimmunoassay,
      respectively. Following evaluation of the results, both cows were treated for 12
      days with Regumate(r) Equine, a synthetic progesterone, during the period of PdG
      dominance. RESULTS: "Mana" accepted the bull 11 days after completion of the
      hormonal treatment, and in December 2011 gave birth to a healthy calf. "Maleika"
      had her first ever oestrus 13 days after completion of the medication and also
      accepted the bull. Thereafter, she had two regular oestrus cycles with normal
      mating behaviour. Her first calf was born in July 2012. CONCLUSION AND CLINICAL
      RELEVANCE: The causal treatment of both cows, following a long period of
      infertility, with synthetic progesterone led to their pregnancy and the birth of
      healthy calves. The commercial product Regumate(r) Equine is appropriate to
      stimulate the sexual cycle in temporarily infertile black rhinos. Attention
      should be paid to the timing of the medication and the required dose.

PMID- 24920089
TI  - [Recurrent clinical mastitis in dairy cattle - importance and causes].
AB  - Clinical mastitis as a frequently recurrent event can cause substantive economic
      loss on dairy farms. The reason for recurrent mastitis can be either a persistent
      infection of the bovine mammary gland by a mastitis pathogen or a reinfection of
      a quarter or udder after bacteriological cure. The virulence properties of a
      mastitis pathogen and the cure odds of an individual cow determine the
      development of persistent infections. Clinical episodes may alternate with
      periods without symptoms in the course of persistent infections. Strategies to
      reduce cases of recurrent mastitis have to include improved treatment concepts
      and measures to decrease new infection rates. The present literature review
      summarises the knowledge of definitions, frequencies, causes and effects of
      recurrent mastitis. 

PMID- 24920090
TI  - [Septicaemia in piglets associated with a positive finding of a methicillin
      resistant S. aureus strain].
AB  - Staphylococcus (S.) aureus has been associated with septicaemia, mastitis,
      vaginitis, metritis, osteomyelitis, and endocarditis. This case report
      demonstrates S. aureus-induced septicaemia in suckling pig- lets. Three days
      after birth, littermates displayed severe ecchymosis and cyanosis, with a 50%
      mortality rate. The surviving littermates were cross-fostered, but died 1 day
      later. Other piglets, which were allowed to suck at the sow, developed similar
      clinical signs. Haematological findings were anaemia, thrombocytopenia, and
      leukopenia; therefore, neither isohaemolytic anaemia nor septicaemia could be
      excluded as differential diagnoses. At necropsy, petechial bleeding on inner
      organ surfaces and free blood in body cavities were found. Bacteriological
      examination of the sow's milk and of the spleen of one piglet detected a
      methicillin-resistent S. aureus strain (MRSA CC398), which was in all likelihood
      the cause of the disease. Potential differential diagnoses are discussed.

PMID- 24920091
TI  - [Cowpox virus infection in an alpaca (Vicugna pacos) - clinical symptoms,
      laboratory diagnostic findings and pathological changes].
AB  - Orthopoxvirus infections appear to be rare in South American Camelids, because
      only a few cases have been reported in the literature. Based on a generalized
      infection with cowpox virus in an alpaca, the clinical symptoms, laboratory
      diagnostic findings and the pathological changes are described. The case history
      showed a long treatment because of chronic skin lesions. The main clinical
      symptom was miliary papules over the entire skin. Furthermore, a bilateral
      mucopurulent conjunctivitis occurred as well as excessive salivation due to a
      severe erosive-ulcerative stomatitis. Although the animal received intensive
      treatment, it died 8 days after admission to the clinic. During necropsy, an
      erosive-ulcerative laryngitis as well as a necrotising pneumonia and
      lymphadenitis were observed. Histopathological examination of representative
      organ samples led to the diagnosis of a suspected orthopoxvirus infection.
      Electron microscopy and quantitative polymerase chain reaction (qPCR) of tissue
      samples confirmed this diagnosis. The virus could be isolated in tissue culture
      and a PCR with subsequent nucleotide sequencing identified cowpox virus as the
      causative agent for this generalised infection.

PMID- 24920092
TI  - [Reproductive disorders in the female pig: causes, manifestation, diagnostics and
      approach in herd health care].
AB  - Reproductive failure is the most common cause for culling sows from production
      herds. These failures can affect individual pigs, but can also be a farm problem.
      Any region of the pig's genital tract can be diseased, with the uterus being the
      most frequently affected organ. Numerous microorganisms and toxins are known to
      cause genital pathology in the sow. Although reproduction problems are considered
      to be multifactorial, recognizing genital pathology is crucial as the first step
      in the diagnostic workup of reproductive disorders. This contribution briefly
      reviews the most common genital disorders in the female pig with respect to
      incidence, pathogenesis and clinical picture. In a second part, the
      gynaecological examination and the steps in the diagnostic workup are presented. 

PMID- 24920093
TI  - Anticancer ruthenium(III) complex KP1019 interferes with ATP-dependent Ca2+
      translocation by sarco-endoplasmic reticulum Ca2+-ATPase (SERCA).
AB  - Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), a P-type ATPase that sustains
      Ca2+ transport and plays a major role in intracellular Ca2+ homeostasis,
      represents a therapeutic target for cancer therapy. Here, we investigated whether
      ruthenium-based anticancer drugs, namely KP1019 (indazolium [trans
      tetrachlorobis(1H-indazole)ruthenate(III)]), NAMI-A (imidazolium [trans
      tetrachloro(1H-imidazole)(S-dimethylsulfoxide)ruthenate(III)]) and RAPTA-C
      ([Ru(eta6-p-cymene)dichloro(1,3,5-triaza-7-phosphaadamantane)]), and cisplatin
      (cis-diammineplatinum(II) dichloride) might act as inhibitors of SERCA. Charge
      displacement by SERCA adsorbed on a solid-supported membrane was measured after
      ATP or Ca2+ concentration jumps. Our results show that KP1019, in contrast to the
      other metal compounds, is able to interfere with ATP-dependent translocation of
      Ca2+ ions. An IC50 value of 1 MUM was determined for inhibition of calcium
      translocation by KP1019. Conversely, it appears that KP1019 does not
      significantly affect Ca2+ binding to the ATPase from the cytoplasmic side.
      Inhibition of SERCA at pharmacologically relevant concentrations may represent a
      crucial aspect in the overall pharmacological and toxicological profile of
      KP1019.

PMID- 24920094
TI  - Rapid two-step synthesis of benzimidazo[1',2':1,5]pyrrolo[2,3-c]isoquinolines by
      a three-component coupling reaction.
AB  - A two-step, three-component coupling reaction on ionic liquid supported 2
      cyanomethylbenzimidazoles, methyl 2-formylbenzoate, and isocyanides under
      microwave activation is explored. Knoevenagel condensation of 2
      cyanomethylbenzimidazole with methyl-2-formylbenzoate in the presence of
      piperidine catalyst is followed by [4+1] cycloaddition with an isocyanide in the
      next step. Consequent intramolecular delta-lactam formation allows rapid
      construction of novel aza-pentacycles, benzimidazo[1',2':1,5]pyrrolo[2,3
      c]isoquinolines.

PMID- 24920095
TI  - 2Loud?: Community mapping of exposure to traffic noise with mobile phones.
AB  - Despite ample medical evidence of the adverse impacts of traffic noise on health,
      most policies for traffic noise management are arbitrary or incomplete, resulting
      in serious social and economic impacts. Surprisingly, there is limited
      information about citizen's exposure to traffic noise worldwide. This paper
      presents the 2Loud? mobile phone application, developed and tested as a
      methodology to monitor, assess and map the level of exposure to traffic noise of
      citizens with focus on the night period and indoor locations, since sleep
      disturbance is one of the major triggers for ill health related to traffic noise.
      Based on a community participation experiment using the 2Loud? mobile phone
      application in a region close to freeways in Australia, the results of this
      research indicates a good level of accuracy for the noise monitoring by mobile
      phones and also demonstrates significant levels of indoor night exposure to
      traffic noise in the study area. The proposed methodology, through the data
      produced and the participatory process involved, can potentially assist in
      planning and management towards healthier urban environments. 

PMID- 24920096
TI  - Trichoderma species fungemia after high-dose chemotherapy and autologous stem
      cell transplantation: a case report.
AB  - We present a case of Trichoderma fungemia with pulmonary involvement in a
      multiple myeloma patient, who was severely immunocompromised and heavily treated
      with high-dose melphalan, and underwent autologous hematopoietic cell
      transplantation. This is the first report, to our knowledge, of proven
      Trichoderma fungemia, defined by published criteria, successfully treated with
      voriconazole.

PMID- 24920098
TI  - How to best forecast adverse outcomes following geriatric trauma: an ageless
      question?

PMID- 24920099
TI  - Antibody- and TRIM21-dependent intracellular restriction of Salmonella enterica.
AB  - TRIM21 ('tripartite motif-containing protein 21', Ro52) is a ubiquitously
      expressed cytosolic Fc receptor, which has a potent role in protective immunity
      against nonenveloped viruses. TRIM21 mediates intracellular neutralisation of
      antibody-coated viruses, a process called ADIN (antibody-dependent intracellular
      neutralisation). Our results reveal a similar mechanism to fight bacterial
      infections. TRIM21 is recruited to the intracellular pathogen Salmonella enterica
      in epithelial cells early in infection. TRIM21 does not bind directly to S.
      enterica, but to antibodies opsonising it. Most importantly, bacterial
      restriction is dependent on TRIM21 as well as on the opsonisation state of the
      bacteria. Finally, Salmonella and TRIM21 colocalise with the autophagosomal
      marker LC3, and intracellular defence is enhanced in starved cells suggesting an
      involvement of the autophagocytic pathway. Our data extend the protective role of
      TRIM21 from viruses to bacteria and thereby strengthening the general role of
      ADIN in cellular immunity.

PMID- 24920100
TI  - Tuberculosis drug discovery and emerging targets.
AB  - Current tuberculosis (TB) therapies take too long and the regimens are complex
      and subject to adverse effects and drug-drug interactions with concomitant
      medications. The emergence of drug-resistant TB strains exacerbates the
      situation. Drug discovery for TB has resurged in recent years, generating
      compounds (hits) with varying potential for progression into developable leads.
      In parallel, advances have been made in understanding TB pathogenesis. It is now
      possible to apply the lessons learned from recent TB hit generation efforts and
      newly validated TB drug targets to generate the next wave of TB drug leads. Use
      of currently underexploited sources of chemical matter and lead-optimization
      strategies may also improve the efficiency of future TB drug discovery. Novel TB
      drug regimens with shorter treatment durations must target all subpopulations of
      Mycobacterium tuberculosis existing in an infection, including those responsible
      for the protracted TB treatment duration. This review proposes strategies for
      generating improved hits and leads that could help achieve this goal. 

PMID- 24920101
TI  - Protonation switching to the least-basic heteroatom of carbamate through cationic
      hydrogen bonding promotes the formation of isocyanate cations.
AB  - We found that phenethylcarbamates that bear ortho-salicylate as an ether group
      (carbamoyl salicylates) dramatically accelerate O?C bond dissociation in strong
      acid to facilitate generation of isocyanate cation (N-protonated isocyanates),
      which undergo subsequent intramolecular aromatic electrophilic cyclization to
      give dihydroisoquinolones. To generate isocyanate cations from carbamates in
      acidic media as electrophiles for aromatic substitution, protonation at the ether
      oxygen, the least basic heteroatom, is essential to promote C?O bond cleavage.
      However, the carbonyl oxygen of carbamates, the most basic site, is protonated
      exclusively in strong acids. We found that the protonation site can be shifted to
      an alternative basic atom by linking methyl salicylate to the ether oxygen of
      carbamate. The methyl ester oxygen ortho to the phenolic (ether) oxygen of
      salicylate is as basic as the carbamate carbonyl oxygen, and we found that
      monoprotonation at the methyl ester oxygen in strong acid resulted in the
      formation of an intramolecular cationic hydrogen bond (>C?O(+) ?H???O<) with the
      phenolic ether oxygen. This facilitates O?C bond dissociation of
      phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast,
      superacid-mediated diprotonation at the methyl ester oxygen of the salicylate and
      the carbonyl oxygen of the carbamate afforded a rather stable dication, which did
      not readily undergo C?O bond dissociation. This is an unprecedented and unknown
      case in which the monocation has greater reactivity than the dication. 

PMID- 24920102
TI  - A mean-field theory on the differential capacitance of asymmetric ionic liquid
      electrolytes.
AB  - The size of ions significantly influences the electric double layer structure of
      room temperature ionic liquid (IL) electrolytes and their differential
      capacitance (Cd). In this study, we extended the mean-field theory (MFT)
      developed independently by Kornyshev (2007J. Phys. Chem. B 111 5545-57) and
      Kilic, Bazant, and Ajdari (2007 Phys. Rev. E 75 021502) (the KKBA MFT) to take
      into account the asymmetric 1:1 IL electrolytes by introducing an additional
      parameter xi for the anion/cation volume ratio, besides the ionic compressibility
      gamma in the KKBA MFT. The MFT of asymmetric ions becomes KKBA MFT upon xi = 1,
      and further reduces to Gouy-Chapman theory in the gamma -> 0 limit. The result of
      the extended MFT demonstrates that the asymmetric ILs give rise to an asymmetric
      Cd, with the higher peak in Cd occurring at positive polarization for the smaller
      anionic size. At high potential, Cd decays asymptotically toward KKBA MFT
      characterized by gamma for the negative polarization, and characterized by
      xigamma for the positive polarization, with inverse-square-root behavior. At low
      potential, around the potential of zero charge, the asymmetric ions cause a
      higher Cd, which exceeds that of Gouy-Chapman theory.

PMID- 24920103
TI  - The role of diffusion tensor imaging in paediatric Chiari I malformation.

PMID- 24920104
TI  - Independent and joint effects of prenatal maternal smoking and maternal exposure
      to second-hand smoke on the development of adolescent obesity: a longitudinal
      study.
AB  - AIM: To examine associations of prenatal maternal smoking and second-hand smoke
      (SHS) exposure with the development of adolescent obesity. METHODS: Longitudinal
      data (1991-2007) from National Institute of Child Health and Human Development
      Study of Early Child Care and Youth Development involving mothers that smoked and
      or exposed to SHS during the year before birth were analysed. Adolescent obesity
      in ages 12.0-15.9 years was defined as a BMI >= 95th percentile. Generalised
      estimating equations (GEE) were used for the analyses. RESULTS: Obesity was more
      prevalent among adolescents whose mothers smoked or had SHS exposure than those
      that did not smoke or exposed to SHS. After adjusting for maternal and child
      factors, GEE models showed that odds of adolescent obesity increased with
      prenatal maternal smoking (OR = 1.57, 95% CI = 1.03-2.39) and SHS exposure (OR =
      1.53, 95% CI = 1.04-2.27). The odds for obesity increased more than two times
      among adolescents exposed to both maternal smoking and SHS (OR = 2.10, 95% CI =
      1.24, 3.56) compared with those without exposure. Additionally, not
      breastfeeding, maternal obesity, and longer screen viewing hours per day were
      associated with increased odds of obesity. CONCLUSIONS: There is possibly a long
      term joint effect of prenatal maternal smoke (smoking and SHS) exposure on
      obesity among adolescent offspring, and the effect is independent of birthweight.
      These findings suggest that adolescent obesity could possibly be curtailed with
      the development and promotion of smoking cessation programmes for families during
      the year before birth.

PMID- 24920106
TI  - Pd-catalyzed ring-opening cross-coupling of cyclopropenes with aryl iodides.
AB  - A transition metal-catalyzed cross-coupling reaction of cyclopropenes with aryl
      iodides proceeds with the opening of the cyclopropene ring, affording 1,3
      butadienes as the products. 

PMID- 24920105
TI  - Enzymatically triggered peptide hydrogels for 3D cell encapsulation and culture.
AB  - We have investigated the possibility of using enzymatically triggered peptide
      hydrogels for the encapsulation and culture of cells. Based on recent work done
      on the enzymatically triggered gelation of FEFK (F, phenylalanine; E, glutamic
      acid; K, lysine) using thermolysin, a protease enzyme from Bacillus
      Thermoproteolyticus Rokko, we have investigated the possibility of using this
      gelation triggering mechanism to encapsulate cells within a 3D hydrogel matrix.
      First, the properties of enzymatically triggered hydrogels prepared in phosphate
      buffer solution were investigated and compared with the properties of hydrogels
      prepared in HPLC grade water from our previous work. We showed that the use of
      phosphate buffer solution allowed the production of hydrogels with very high
      shear moduli (>1 MPa). The gelation kinetics was also investigated, and the
      mechanical properties of the system were shown to closely follow the synthesis of
      the octapeptide by the enzyme through reverse hydrolysis. In a second phase, we
      developed, on the basis of information acquired, a facile protocol for the
      encapsulation of cells and plating of the hydrogel. Human dermal fibroblasts were
      then used to exemplify the use of these materials. FEFEFKFK octapeptide hydrogels
      prepared under the same conditions and with the same mechanical properties were
      used as a control. We showed that no significant differences were observed
      between the two systems and that after a decrease in cell number on day 1, cells
      start to proliferate. After 5 days of culture, the cells can be seen to start to
      adopt a stretched morphology typical of fibroblasts. The results clearly show
      that the protocol developed minimises the potential detrimental effect that
      thermolysin can have on the cells and that these enzymatically triggered
      hydrogels can be used for the 3D encapsulation and culture of cells.

PMID- 24920107
TI  - Transoesophageal echocardiography for prediction of postoperative atrial
      fibrillation after isolated aortic valve replacement: two-dimensional speckle
      tracking for intraoperative assessment of left ventricular longitudinal strain.
AB  - OBJECTIVES: Recent studies suggested association between impaired left
      ventricular long-axis function and arrhythmic events early after open heart
      surgery. This prospective study investigated the predictive value of a depressed
      intraoperative global longitudinal strain (GLS) for postoperative atrial
      fibrillation after isolated aortic valve replacement in patients with preserved
      ejection fraction. METHODS: A total of 107 patients with ejection fraction >=50%
      and moderate-to-severe aortic stenosis undergoing isolated aortic valve
      replacement were enrolled. All patients underwent intraoperative transoesophageal
      echocardiography before surgical incision (T1) and after closure of the
      sternotomy (T2) with semiautomated measurement of GLS, and were followed for the
      occurrence of postoperative atrial fibrillation during the hospitalization.
      RESULTS: The incidence of postoperative atrial fibrillation was 37/107 (34.6%).
      Patients with postoperative atrial fibrillation were associated with increased
      length of hospitalization and a higher risk of low cardiac output syndrome and
      pulmonary complications. On univariate analysis, significant risk factors
      associated with postoperative atrial fibrillation were E/e' ratio, left atrial
      volume index (LAVi), GLST2 and DeltaGLS%. On multivariable analysis, GLST2 (odds
      ratio: 1.21; 95% confidence interval (CI): 1.06-1.56, P = 0.031) and DeltaGLS%
      (odds ratio: 3.66; 95% CI: 1.85-6.79, P = 0.001) were independent predictors of
      postoperative atrial fibrillation. The best cut-off values for the prediction
      were GLST2 >-12.75% and DeltaGLS% >19.50%, the latter of which had incremental
      predictive value for postoperative atrial fibrillation. CONCLUSIONS: A
      significant reduction of intraoperative GLS provides independent information for
      predicting postoperative atrial fibrillation in patients undergoing aortic valve
      replacement, and may help to identify patients who are most likely to benefit
      from targeted prophylaxis.

PMID- 24920108
TI  - Underwater attachment using hairs: the functioning of spatula and sucker setae
      from male diving beetles.
AB  - Males of Dytiscinae beetles use specialized adhesive setae to adhere to female
      elytra during underwater courtship. This coevolution of male setae and female
      elytra has attracted much attention since Darwin. However, there has been little
      examination of their biomechanical functioning despite increasing knowledge on
      biofibrillar adhesion. Here, we report and compare, for the first time, the
      mechanisms of underwater attachment using two hair types, the primitive spatula
      and derived 'passive' sucker, found in male diving beetles. Results from
      interspecific scaling of protarsal palettes and adhesion by single seta suggest
      better performance in the later-evolved circular (sucker) setae. Spatula setae
      with a modified shallow sucker and channels use the combined mechanisms of
      suction and viscous resistance for adhesion. Velocity-dependent adhesion provides
      sufficient control for resisting the female's erratic movements while also
      detaching easily through slow peeling. Direction-dependent shear resistance helps
      reorient setae surfaces into a preferred direction for effective adhesion. Seta
      deformation using different mechanisms for circular and spatula setae reduces the
      force that is transmitted to the contact interface. A softer spring in spatula
      setae explains their adhesion at lower preloads and assists in complete substrate
      contact. Attachment mechanisms revealed in adhesive setae with modified spatula
      and passive suckers provide insights for bioinspired designs of underwater
      attachment devices. 

PMID- 24920109
TI  - Fractional diffusion models of cardiac electrical propagation: role of structural
      heterogeneity in dispersion of repolarization.
AB  - Impulse propagation in biological tissues is known to be modulated by structural
      heterogeneity. In cardiac muscle, improved understanding on how this
      heterogeneity influences electrical spread is key to advancing our interpretation
      of dispersion of repolarization. We propose fractional diffusion models as a
      novel mathematical description of structurally heterogeneous excitable media, as
      a means of representing the modulation of the total electric field by the
      secondary electrical sources associated with tissue inhomogeneities. Our results,
      analysed against in vivo human recordings and experimental data of different
      animal species, indicate that structural heterogeneity underlies relevant
      characteristics of cardiac electrical propagation at tissue level. These include
      conduction effects on action potential (AP) morphology, the shortening of AP
      duration along the activation pathway and the progressive modulation by premature
      beats of spatial patterns of dispersion of repolarization. The proposed approach
      may also have important implications in other research fields involving excitable
      complex media. 

PMID- 24920110
TI  - Quantitative analyses of the plant cytoskeleton reveal underlying organizational
      principles.
AB  - The actin and microtubule (MT) cytoskeletons are vital structures for cell growth
      and development across all species. While individual molecular mechanisms
      underpinning actin and MT dynamics have been intensively studied, principles that
      govern the cytoskeleton organization remain largely unexplored. Here, we captured
      biologically relevant characteristics of the plant cytoskeleton through a network
      driven imaging-based approach allowing us to quantitatively assess dynamic
      features of the cytoskeleton. By introducing suitable null models, we demonstrate
      that the plant cytoskeletal networks exhibit properties required for efficient
      transport, namely, short average path lengths and high robustness. We further
      show that these advantageous features are maintained during temporal cytoskeletal
      rearrangements. Interestingly, man-made transportation networks exhibit similar
      properties, suggesting general laws of network organization supporting diverse
      transport processes. The proposed network-driven analysis can be readily used to
      identify organizational principles of cytoskeletons in other organisms. 

PMID- 24920111
TI  - The transition mechanism of DNA overstretching: a microscopic view using
      molecular dynamics.
AB  - The overstretching transition in torsionally unconstrained DNA is studied by
      means of atomistic molecular dynamics simulations. The free-energy profile as a
      function of the length of the molecule is determined through the umbrella
      sampling technique providing both a thermodynamic and a structural
      characterization of the transition pathway. The zero-force free-energy profile is
      monotonic but, in accordance with recent experimental evidence, becomes two-state
      at high forces. A number of experimental results are satisfactorily predicted:
      (i) the entropic and enthalpic contributions to the free-energy difference
      between the basic (B) state and the extended (S) state; (ii) the longitudinal
      extension of the transition state and (iii) the enthalpic contribution to the
      transition barrier. A structural explanation of the experimental finding that
      overstretching is a cooperative reaction characterized by elementary units of
      approximately 22 base pairs is found in the average distance between
      adenine/thymine-rich regions along the molecule. The overstretched DNA adopts a
      highly dynamical and structurally disordered double-stranded conformation which
      is characterized by residual base pairing, formation of non-native intra-strand
      hydrogen bonds and effective hydrophobic screening of apolar regions. 

PMID- 24920112
TI  - Computational modelling suggests good, bad and ugly roles of glycosaminoglycans
      in arterial wall mechanics and mechanobiology.
AB  - The medial layer of large arteries contains aggregates of the glycosaminoglycan
      hyaluronan and the proteoglycan versican. It is increasingly thought that these
      aggregates play important mechanical and mechanobiological roles despite
      constituting only a small fraction of the normal arterial wall. In this paper, we
      offer a new hypothesis that normal aggregates of hyaluronan and versican
      pressurize the intralamellar spaces, and thereby put into tension the radial
      elastic fibres that connect the smooth muscle cells to the elastic laminae, which
      would facilitate mechanosensing. This hypothesis is supported by novel
      computational simulations using two complementary models, a mechanistically based
      finite-element mixture model and a phenomenologically motivated continuum
      hyperelastic model. That is, the simulations suggest that normal aggregates of
      glycosaminoglycans/proteoglycans within the arterial media may play equally
      important roles in supporting (i.e. a structural role) and sensing (i.e. an
      instructional role) mechanical loads. Additional simulations suggest further,
      however, that abnormal increases in these aggregates, either distributed or
      localized, may over-pressurize the intralamellar units. We submit that these
      situations could lead to compromised mechanosensing, anoikis and/or reduced
      structural integrity, each of which represent fundamental aspects of arterial
      pathologies seen, for example, in hypertension, ageing and thoracic aortic
      aneurysms and dissections. 

PMID- 24920113
TI  - The role of mechanical forces in the planar-to-bulk transition in growing
      Escherichia coli microcolonies.
AB  - Mechanical forces are obviously important in the assembly of three-dimensional
      multicellular structures, but their detailed role is often unclear. We have used
      growing microcolonies of the bacterium Escherichia coli to investigate the role
      of mechanical forces in the transition from two-dimensional growth (on the
      interface between a hard surface and a soft agarose pad) to three-dimensional
      growth (invasion of the agarose). We measure the position within the colony where
      the invasion transition happens, the cell density within the colony and the
      colony size at the transition as functions of the concentration of the agarose.
      We use a phenomenological theory, combined with individual-based computer
      simulations, to show how mechanical forces acting between the bacterial cells,
      and between the bacteria and the surrounding matrix, lead to the complex
      phenomena observed in our experiments-in particular the observation that agarose
      concentration non-trivially affects the colony size at transition. Matching these
      approaches leads to a prediction for how the friction between the bacteria and
      the agarose should vary with agarose concentration. Our experimental conditions
      mimic numerous clinical and environmental scenarios in which bacteria invade soft
      matrices, as well as shedding more general light on the transition between two-
      and three-dimensional growth in multicellular assemblies. 

PMID- 24920114
TI  - A computational method to differentiate normal individuals, osteoarthritis and
      rheumatoid arthritis patients using serum biomarkers.
AB  - The objective of this study was to develop a method for categorizing normal
      individuals (normal, n = 100) as well as patients with osteoarthritis (OA, n =
      100), and rheumatoid arthritis (RA, n = 100) based on a panel of inflammatory
      cytokines expressed in serum samples. Two panels of inflammatory proteins were
      used as training sets in the construction of two separate artificial neural
      networks (ANNs). The first training set consisted of all proteins (38 in total)
      and the second consisted of only the significantly different proteins expressed
      (12 in total) between at least two patient groups. Both ANNs obtained high levels
      of sensitivity and specificity, with the first and second ANN each diagnosing
      100% of test set patients correctly. These results were then verified by re
      investigating the entire dataset using a decision tree algorithm. We show that
      ANNs can be used for the accurate differentiation between serum samples of
      patients with OA, a diagnosed RA patient comparator cohort and normal/control
      cohort. Using neural network and systems biology approaches to manage large
      datasets derived from high-throughput proteomics should be further explored and
      considered for diagnosing diseases with complex pathologies. 

PMID- 24920115
TI  - A biomimetic accelerometer inspired by the cricket's clavate hair.
AB  - Crickets use so-called clavate hairs to sense (gravitational) acceleration to
      obtain information on their orientation. Inspired by this clavate hair system, a
      one-axis biomimetic accelerometer has been developed and fabricated using surface
      micromachining and SU-8 lithography. An analytical model is presented for the
      design of the accelerometer, and guidelines are derived to reduce responsivity
      due to flow-induced contributions to the accelerometer's output. Measurements
      show that this microelectromechanical systems (MEMS) hair-based accelerometer has
      a resonance frequency of 320 Hz, a detection threshold of 0.10 ms(-2) and a
      dynamic range of more than 35 dB. The accelerometer exhibits a clear directional
      response to external accelerations and a low responsivity to airflow. Further,
      the accelerometer's physical limits with respect to noise levels are addressed
      and the possibility for short-term adaptation of the sensor to the environment is
      discussed. 

PMID- 24920116
TI  - Extinction risk and eco-evolutionary dynamics in a variable environment with
      increasing frequency of extreme events.
AB  - One of the most dramatic consequences of climate change will be the
      intensification and increased frequency of extreme events. I used numerical
      simulations to understand and predict the consequences of directional trend (i.e.
      mean state) and increased variability of a climate variable (e.g. temperature),
      increased probability of occurrence of point extreme events (e.g. floods),
      selection pressure and effect size of mutations on a quantitative trait
      determining individual fitness, as well as the their effects on the population
      and genetic dynamics of a population of moderate size. The interaction among
      climate trend, variability and probability of point extremes had a minor effect
      on risk of extinction, time to extinction and distribution of the trait after
      accounting for their independent effects. The survival chances of a population
      strongly and linearly decreased with increasing strength of selection, as well as
      with increasing climate trend and variability. Mutation amplitude had no effects
      on extinction risk, time to extinction or genetic adaptation to the new climate.
      Climate trend and strength of selection largely determined the shift of the mean
      phenotype in the population. The extinction or persistence of the populations in
      an 'extinction window' of 10 years was well predicted by a simple model including
      mean population size and mean genetic variance over a 10-year time frame
      preceding the 'extinction window', although genetic variance had a smaller role
      than population size in predicting contemporary risk of extinction. 

PMID- 24920118
TI  - Equilibrium distributions of simple biochemical reaction systems for time-scale
      separation in stochastic reaction networks.
AB  - Many biochemical reaction networks are inherently multiscale in time and in the
      counts of participating molecular species. A standard technique to treat
      different time scales in the stochastic kinetics framework is averaging or quasi
      steady-state analysis: it is assumed that the fast dynamics reaches its
      equilibrium (stationary) distribution on a time scale where the slowly varying
      molecular counts are unlikely to have changed. We derive analytic equilibrium
      distributions for various simple biochemical systems, such as enzymatic reactions
      and gene regulation models. These can be directly inserted into simulations of
      the slow time-scale dynamics. They also provide insight into the stimulus
      response of these systems. An important model for which we derive the analytic
      equilibrium distribution is the binding of dimer transcription factors (TFs) that
      first have to form from monomers. This gene regulation mechanism is compared to
      the cases of the binding of simple monomer TFs to one gene or to multiple copies
      of a gene, and to the cases of the cooperative binding of two or multiple TFs to
      a gene. The results apply equally to ligands binding to enzyme molecules. 

PMID- 24920119
TI  - Automated, contour-based tracking and analysis of cell behaviour over long time
      scales in environments of varying complexity and cell density.
AB  - Understanding single and collective cell motility in model environments is
      foundational to many current research efforts in biology and bioengineering. To
      elucidate subtle differences in cell behaviour despite cell-to-cell variability,
      we introduce an algorithm for tracking large numbers of cells for long time
      periods and present a set of physics-based metrics that quantify differences in
      cell trajectories. Our algorithm, termed automated contour-based tracking for in
      vitro environments (ACTIVE), was designed for adherent cell populations subject
      to nuclear staining or transfection. ACTIVE is distinct from existing tracking
      software because it accommodates both variability in image intensity and multi
      cell interactions, such as divisions and occlusions. When applied to low-contrast
      images from live-cell experiments, ACTIVE reduced error in analysing cell
      occlusion events by as much as 43% compared with a benchmark-tracking program
      while simultaneously tracking cell divisions and resulting daughter-daughter cell
      relationships. The large dataset generated by ACTIVE allowed us to develop
      metrics that capture subtle differences between cell trajectories on different
      substrates. We present cell motility data for thousands of cells studied at
      varying densities on shape-memory-polymer-based nanotopographies and identify
      several quantitative differences, including an unanticipated difference between
      two 'control' substrates. We expect that ACTIVE will be immediately useful to
      researchers who require accurate, long-time-scale motility data for many cells. 

PMID- 24920121
TI  - Corrigendum.

PMID- 24920120
TI  - Detachment of compliant films adhered to stiff substrates via van der Waals
      interactions: role of frictional sliding during peeling.
AB  - The remarkable ability of some plants and animals to cling strongly to substrates
      despite relatively weak interfacial bonds has important implications for the
      development of synthetic adhesives. Here, we examine the origins of large
      detachment forces using a thin elastomer tape adhered to a glass slide via van
      der Waals interactions, which serves as a model system for geckos, mussels and
      ivy. The forces required for peeling of the tape are shown to be a strong
      function of the angle of peeling, which is a consequence of frictional sliding at
      the edge of attachment that serves to dissipate energy that would otherwise drive
      detachment. Experiments and theory demonstrate that proper accounting for
      frictional sliding leads to an inferred work of adhesion of only approximately
      0.5 J m(-2) (defined for purely normal separations) for all load orientations.
      This starkly contrasts with the interface energies inferred using conventional
      interface fracture models that assume pure sticking behaviour, which are
      considerably larger and shown to depend not only on the mode-mixity, but also on
      the magnitude of the mode-I stress intensity factor. The implications for
      developing frameworks to predict detachment forces in the presence of interface
      sliding are briefly discussed. 

PMID- 24920122
TI  - Heart rate slopes during 6-min walk test in pulmonary arterial hypertension,
      other lung diseases, and healthy controls.
AB  - Six-minute walk test (6MWT) continues to be a useful tool to determine the
      functional capacity in patients with vascular and other lung diseases;
      nevertheless, it has a limited ability to predict prognosis in this context. We
      tested whether the heart rate (HR) acceleration and decay slopes during the 6-m
      walk test are different in patients with pulmonary arterial hypertension (PAH),
      other lung diseases, and healthy controls. In addition, we assessed whether the
      HR slopes are associated with clinical worsening. Using a portable, signal
      morphology-based, impedance cardiograph (PhysioFlow Enduro, Paris, France) with
      real-time wireless monitoring via a Bluetooth USB adapter we determined beat-by
      beat HR. We included 50 subjects in this pilot study, 20 with PAH (all on PAH
      specific treatment), 17 with other lung diseases (obstructive [n = 12, 71%] or
      restrictive lung diseases [5, 29%]), and 13 healthy controls. The beat-by-beat HR
      curves were significantly different among all three groups of subjects either
      during the activity or recovery of the 6MWT. HR curves were less steep in PAH
      than the other two groups (P < 0.001). HR acceleration rates were slower in
      patients with PAH or other lung diseases with progression of their disease (P <
      0.001). In conclusion, the acceleration and decay slopes during 6MWT are
      different among patients with PAH, other lung diseases, and healthy controls. The
      HR slopes during 6MWT were steeper in patients without clinical worsening. 

PMID- 24920123
TI  - A role for the age-dependent loss of alpha(E)-catenin in regulation of N-cadherin
      expression and cell migration.
AB  - The aging kidney has a decreased ability to repair following acute kidney injury.
      Previous studies from our laboratory have demonstrated a loss in alpha-catenin
      expression in the aging rat kidney. We hypothesize that loss of alpha-catenin
      expression in tubular epithelial cells may induce changes that result in a
      decreased repair capacity. In these studies, we demonstrate that decreased alpha
      catenin protein expression is detectable as early as 20 months of age in male
      Fischer 344 rats. Protein loss is also observed in aged nonhuman primate kidneys,
      suggesting that this is not a species-specific response. In an effort to
      elucidate alterations due to the loss of alpha-catenin, we generated NRK-52E cell
      lines with stable knockdown of alpha(E)-catenin (C2 cells). Interestingly, C2
      cells had decreased expression of N-cadherin, decreased cell-cell adhesion, and
      increased monolayer permeability. C2 had deficits in wound repair, due to
      alterations in cell migration. Analysis of gene expression in the migrating
      control cells indicated that expression of N-cadherin and N-CAM was increased
      during repair. In migrating C2 cells, expression of N-CAM was also increased, but
      the expression of N-cadherin was not upregulated. Importantly, a blocking
      antibody against N-cadherin inhibited repair in NRK-52E cells, suggesting an
      important role in repair. Taken together, these data suggest that loss of alpha
      catenin, and the subsequent downregulation of N-cadherin expression, is a
      mechanism underlying the decreased migration of tubular epithelial cells that
      contributes to the inability of the aging kidney to repair following injury. 

PMID- 24920124
TI  - Cytochrome P4504A inhibitors attenuate the exaggerated natriuretic response to
      volume expansion in thyroidectomized rats.
AB  - Thyroidectomy augments the natriuretic response to volume expansion; however, the
      mechanism remains unknown. This study assessed the role of 20
      hydroxyeicosatetraenoic acid (20-HETE) in the natriuretic response to an acute
      volume expansion in hypothyroid rats. Urine flow (1.9-fold), sodium excretion
      (2.4-fold), fractional sodium excretion (3.8-fold), and distal delivery of sodium
      (4.1-fold) increased to a greater extent in thyroidectomized rats (TX) than in
      sham-operated controls (SHAM) following i.v. infusion of isotonic saline (5% body
      weight) over 60 min. This was associated with inhibition of both proximal and
      distal tubular reabsorption of sodium. Administration of two mechanistic and
      chemical dissimilar inhibitors of the synthesis of 20-HETE, 1-aminobenzotriazole
      (ABT), and N-hydroxy-N'-(-4-butyl-2-methylphenyl)formamidine (HET0016) decreased
      the natriuretic response in TX rats. Glomerular filtration rate was lower in TX
      than in SHAM rats and was not altered by the CYP4A inhibitors. The expression,
      intrarenal distribution, and the formation of 20-HETE and expoxygenase
      metabolites of arachidonic acid were similar in the cortex and medulla of SHAM
      and TX rats. These results suggest that CYP4A-derived metabolites of arachidonic
      acid play an important role in the enhanced natriuretic response to volume
      expansion in hypothyroid rats even though TX did not alter the expression or
      activity of these enzymes. 

PMID- 24920126
TI  - Reciprocal activation of gastrocnemius and soleus motor units is associated with
      fascicle length change during knee flexion.
AB  - While medial gastrocnemius (MG) and soleus (SOL) are considered synergists, they
      are anatomically exclusive in that SOL crosses only the ankle, while MG crosses
      both the knee and ankle. Due to the force-length properties of both active and
      passive structures, activation of SOL and MG must be constantly regulated to
      provide the required joint torques for any planned movement. As such, the aim of
      this study was to investigate the neural regulation of MG and SOL when
      independently changing their length by changing only the knee joint angle, thus
      exclusively altering the length of MG fibers. MG and SOL motor units (MU) were
      recorded intramuscularly along with ultrasound imaging of MG and SOL fascicle
      lengths, while moving the knee through 60 degrees  of rotation and maintaining a
      low level of voluntary plantar flexor torque. The results showed a reciprocal
      activation of MG and SOL as the knee was moved into flexion and extension. A
      clear reduction in MG MU firing rates occurred as the knee was flexed (MG
      fascicles shortening), with de-recruitment of most MG MU occurring at close to
      full knee flexion. A concomitant increase in SOL MU activity was observed while
      no change in the length of its fascicles was found. The opposite effects were
      found when the knee was moved into extension. A strong correlation (ICC = 0.78)
      was found between the fascicle length at which MG MUs were de-recruited and
      subsequently re-recruited. This was stronger than the relationship of de
      recruitment and re-recruitment with knee angle (ICC = 0.52), indicating that in
      this instance, muscle fascicle length rather than joint angle is more influential
      in regulating MG recruitment. Such a reciprocal arrangement like the one
      presented here for SOL and MG is essential for human voluntary movements such as
      walking or cycling. 

PMID- 24920127
TI  - Determination of aristolochic acids by high-performance liquid chromatography
      with fluorescence detection.
AB  - Nephrotoxic and carcinogenic aristolochic acids (AAs) are naturally occurring
      nitrophenanthrene carboxylic acids in the herbal genus Aristolochia. The misuse
      of AA-containing herbs in preparing slimming drugs has caused hundred of cases of
      kidney disease in Belgium women in a slimming regime in the early 1990s.
      Accumulating evidence also suggested that prolong dietary intake of AA
      contaminated food is one of the major causes to the Balkan endemic nephropathy
      that was first observed in the late 1950s. Therefore, analytical methods of high
      sensitivity are extremely important for safeguarding human exposure to AA
      containing herbal medicines, herbal remedies, and food composites. In this paper,
      we describe the development of a new high-performance liquid chromatography
      coupled fluorescence detector (HPLC-FLD) method for the sensitive determination
      of AAs. The method makes use of a novel cysteine-induced denitration reaction
      that "turns on" the fluorescence of AAs for fluorometric detections. Our results
      showed that the combination of cysteine-induced denitration and HPLC-FLD analysis
      allows for sensitive quantification of AA-I and AA-II at detection limits of 27.1
      and 25.4 ng/g, respectively. The method was validated and has been successfully
      applied in quantifying AAs in Chinese herbal medicines. 

PMID- 24920125
TI  - Differential effects of glyoxalase 1 overexpression on diabetic atherosclerosis
      and renal dysfunction in streptozotocin-treated, apolipoprotein E-deficient mice.
AB  - The reactive dicarbonyls, glyoxal and methylglyoxal (MG), increase in diabetes
      and may participate in the development of diabetic complications. Glyoxal and MG
      are detoxified by the sequential activities of glyoxalase 1 (GLO1) and glyoxalase
      2. To determine the contribution of these dicarbonyls to the etiology of
      complications, we have genetically manipulated GLO1 levels in apolipoprotein E
      null (Apoe(-/-)) mice. Male Apoe(-/-) mice, hemizygous for a human GLO1 transgene
      (GLO1TGApoe(-/-) mice) or male nontransgenic Apoe(-/-) litter mates were injected
      with streptozotocin or vehicle and 6 or 20 weeks later, aortic atherosclerosis
      was quantified. The GLO1 transgene lessened streptozotocin (STZ)-induced
      increases in immunoreactive hydroimidazolone (MG-H1). Compared to nondiabetic
      mice, STZ-treated GLO1TGApoe(-/-) and Apoe(-/-) mice had increased serum
      cholesterol and triglycerides and increased atherosclerosis at both times after
      diabetes induction. While the increased GLO1 activity in the GLO1TGApoe(-/-) mice
      failed to protect against diabetic atherosclerosis, it lessened glomerular
      mesangial expansion, prevented albuminuria and lowered renal levels of
      dicarbonyls and protein glycation adducts. Aortic atherosclerosis was also
      quantified in 22-week-old, male normoglycemic Glo1 knockdown mice on an Apoe(-/-)
      background (Glo1KDApoe(-/-) mice), an age at which Glo1KD mice exhibit
      albuminuria and renal pathology similar to that of diabetic mice. In spite of
      ~75% decrease in GLO1 activity and increased aortic MG-H1, the Glo1KDApoe(-/-)
      mice did not show increased atherosclerosis compared to age-matched Apoe(-/-)
      mice. Thus, manipulation of GLO1 activity does not affect the development of
      early aortic atherosclerosis in Apoe(-/-) mice but can dictate the onset of
      kidney disease independently of blood glucose levels. 

PMID- 24920128
TI  - Comparing segmented ASL perfusion of vascular territories using manual versus
      semiautomated techniques in children with sickle cell anemia.
AB  - PURPOSE: Elevated cerebral blood flow (CBF) in sickle cell anemia (SCA) is an
      adaptive pathophysiologic response associated with decreased vascular reserve and
      increased risk for ischemia. We compared manual (M) and semiautomated (SA)
      vascular territory delineation to facilitate standardized evaluation of CBF in
      children with SCA. MATERIALS AND METHODS: ASL perfusion values from 21 children
      were compared for gray matter and white matter (WM) in vascular territories
      defined by M and SA delineation. SA delineated CBF was compared with clinical and
      hematologic variables acquired within 4 weeks of the MRI. RESULTS: CBF
      measurements from M (MCA 82 left, 79 right) and SA (MCA 81 left, 81 right)
      delineated territories were highly correlated (R = 0.99, P < 0.0001). Bland
      Altman plots had close-fitting limits of agreement of -1.8 to -3.5 lower limit
      and 0 to 1.8 upper limit. SA vascular territory delineation was comparable to the
      expert delineation with a kappa index of 0.62-0.85 and was considerably faster.
      Median territorial CBF values did not differ by gender or age. WM perfusion in
      the posterior cerebral artery territories was positively correlated with degree
      of hemolysis (R = 0.58, P = 0.01 left, 0.73, P < 0.001 right) and negatively
      correlated with hemoglobin (R = -0.48; P = 0.03 left; -0.47; P = 0.04 right) and
      hemoglobin F (R = -0.42; P = .09 left; -0.47; P = 0.049 right). CONCLUSION: We
      established the validity of the SA method, which in our experience was much
      faster than the M method for delineation of vascular territories. Associations
      between CBF and hematologic variables may demonstrate pathophysiologic changes
      that contribute to clinical variation in CBF.

PMID- 24920129
TI  - Antioxidant status in blood of obese children: the relation between trace
      elements, paraoxonase, and arylesterase values.
AB  - Obesity is known to lead to complications involving several systems. The basic
      mechanism in obesity-related complications is chronic inflammation and increased
      oxidative stress. Trace element levels in obese children may vary due to poor
      nutritional habits. The purpose of this study was to investigate the relation
      between serum paraoxonase (PON1) and arylesterase (ARE) levels, markers of the
      oxidant-antioxidant balance in the body, and serum zinc (Zn), copper (Cu),
      manganese (Mn), and selenium (Se) concentrations in obese children. Fifty-seven
      overweight patients aged 6-17 and 48 age- and sex-matched healthy children were
      included in the study. Serum PON1 and ARE activity levels were measured, together
      with Cu, Zn, Mn, Se, total cholesterol, triglyceride, low-density lipoprotein,
      high-density lipoprotein, very low-density lipoprotein, glucose, aspartate amino
      transferase, and alanine amino transferase levels. PON1 and ARE activity levels
      were significantly lower in obese patients compared to those in healthy
      individuals (P < 0.05). Various changes were determined in Cu, Zn, Mn, and Se
      levels between the study and control groups (P < 0.05). In terms of the relation
      between trace elements and PON1 and ARE levels, a significant positive
      correlation was determined between serum Se and PON1 levels in the study group (P
      < 0.05, r = 0.31). No significant correlation was determined between other trace
      element levels and PON1 and ARE levels (P > 0.05). In conclusion, the detection
      in our study of a positive correlation between Se and PON1 levels in obese
      children may be significant in terms of showing a relation between Se and
      antioxidant systems in obese children.

PMID- 24920130
TI  - Cu(2+) inhibits photosystem II activities but enhances photosystem I quantum
      yield of Microcystis aeruginosa.
AB  - Responses of photosystem I and II activities of Microcystis aeruginosa to various
      concentrations of Cu(2+) were simultaneously examined using a Dual-PAM-100
      fluorometer. Cell growth and contents of chlorophyll a were significantly
      inhibited by Cu(2+). Photosystem II activity [Y(II)] and electron transport
      [rETRmax(II)] were significantly altered by Cu(2+). The quantum yield of
      photosystem II [Y(II)] decreased by 29 % at 100 MUg L(-1) Cu(2+) compared to
      control. On the contrary, photosystem I was stable under Cu(2+) stress and showed
      an obvious increase of quantum yield [Y(I)] and electron transport [rETRmax(I)]
      due to activation of cyclic electron flow (CEF). Yield of cyclic electron flow
      [Y(CEF)] was enhanced by 17 % at 100 MUg L(-1) Cu(2+) compared to control. The
      contribution of linear electron flow to photosystem I [Y(II)/Y(I)] decreased with
      increasing Cu(2+) concentration. Yield of cyclic electron flow [Y(CEF)] was
      negatively correlated with the maximal photosystem II photochemical efficiency (F
      v/F m). In summary, photosystem II was the major target sites of toxicity of
      Cu(2+), while photosystem I activity was enhanced under Cu(2+) stress.

PMID- 24920131
TI  - Effect of charge density of polysaccharides on self-assembled intragastric
      gelation of whey protein/polysaccharide under simulated gastric conditions.
AB  - This study focuses on the behavior of mixed protein and polysaccharides with
      different charge densities under simulated gastric conditions. Three types of
      polysaccharides, namely, guar gum, xanthan gum and carrageenan (neutral, medium
      negatively, and highly negatively charged, respectively) were selected for
      heating together with whey protein isolate (WPI) at a biopolymer ratio ranging
      from 0.01 to 0.1. Upon mixing with simulated gastric fluid (SGF), all WPI-guar
      gum samples remained soluble, whereas WPI-xanthan gum and WPI-carrageenan at
      biopolymer ratio higher than 0.01 led to self-assembled intragastric gelation
      immediately after mixing with SGF. The mechanism behind the intragastric gelation
      is believed to be the cross-linking between oppositely charged protein and
      polysaccharides when pH was reduced to below the pI of the protein. Higher
      biopolymer ratio led to a higher degree of intermolecular interaction, which
      tends to form stronger gel. More negatively charged carrageenan also formed a
      stronger gel than xanthan gum. SDS-PAGE results show that the digestibility of
      protein was not affected by the presence of guar gum as well as xanthan gum and
      carrageenan at biopolymer ratio lower than 0.02. However, intragastric gel formed
      by WPI-xanthan gum and WPI-carrageenan at biopolymer ratio higher than 0.02
      significantly slows down the digestion rate of protein, which could potentially
      be used to delay gastric emptying and promote satiety. 

PMID- 24920132
TI  - Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore
      opening.
AB  - In voltage-gated K(+) channels, membrane depolarization induces an upward
      movement of the voltage-sensing domains (VSD) that triggers pore opening. KCNQ1
      is a voltage-gated K(+) channel and its gating behaviour is substantially
      modulated by auxiliary subunit KCNE proteins. KCNE1, for example, markedly shifts
      the voltage dependence of KCNQ1 towards the positive direction and slows down the
      activation kinetics. Here we identify two phenylalanine residues on KCNQ1, Phe232
      on S4 (VSD) and Phe279 on S5 (pore domain) to be responsible for the gating
      modulation by KCNE1. Phe232 collides with Phe279 during the course of the VSD
      movement and hinders KCNQ1 channel from opening in the presence of KCNE1. This
      steric hindrance caused by the bulky amino-acid residues destabilizes the open
      state and thus shifts the voltage dependence of KCNQ1/KCNE1 channel. 

PMID- 24920133
TI  - Neuropsychological performance of methadone-maintained opiate users.
AB  - Methadone maintenance treatment (MMT) has been used to treat opiate dependence
      since the mid-1960s. Previous studies have investigated the effects of methadone
      on cognitive function however the findings have been inconsistent. Some report a
      complete absence of deficits while others report different types of cognitive
      impairment. Our research aimed to investigate the effects of MMT on cognitive
      function by comparing the performance of patients currently enrolled in MMT
      (n=32) with opiate-dependent subjects (n=17) and healthy control subjects (n=25)
      on a computerised neuropsychological test battery. Both the patients undertaking
      MMT and the opiate users showed less efficient interaction between visual
      searching and manually connecting digits and letters during the Switching of
      Attention Task than the healthy control subjects (F(2,64)=3.25, p=0.05), which
      indicates deficits in information processing. Nevertheless, the performance of
      the MMT group was similar to that of healthy control subjects in all other tasks,
      in contrast to the group of opiate users who performed poorly when compared to
      healthy control subjects during tests of attention (mean difference (MD)=2.8, 95%
      confidence interval (CI) (0.9-4.7), p=0.001) and executive function (MD=5.9, 95%
      CI (1.3-10.5), p=0.007). These findings suggest that cognitive function in
      patients undertaking MMT is improved compared to those dependent on illicit
      opiates. 

PMID- 24920134
TI  - The use of magnetoencephalography in the study of psychopharmacology (pharmaco
      MEG).
AB  - Magnetoencephalography (MEG) is a neuroimaging technique that allows direct
      measurement of the magnetic fields generated by synchronised ionic neural
      currents in the brain with moderately good spatial resolution and high temporal
      resolution. Because chemical neuromodulation can cause changes in neuronal
      processing on the millisecond time-scale, the combination of MEG with
      pharmacological interventions (pharmaco-MEG) is a powerful tool for measuring the
      effects of experimental modulations of neurotransmission in the living human
      brain. Importantly, pharmaco-MEG can be used in both healthy humans to understand
      normal brain function and in patients to understand brain pathologies and drug
      treatment effects. In this paper, the physiological and technical basis of
      pharmaco-MEG is introduced and contrasted with other pharmacological neuroimaging
      techniques. Ongoing developments in MEG analysis techniques such as source
      localisation, functional and effective connectivity analyses, which have allowed
      for more powerful inferences to be made with recent pharmaco-MEG data, are
      described. Studies which have utilised pharmaco-MEG across a range of
      neurotransmitter systems (GABA, glutamate, acetylcholine, dopamine and serotonin)
      are reviewed. 

PMID- 24920137
TI  - Obesity, liberty, and public health emergencies.

PMID- 24920136
TI  - Plurality of anxiety and depression alteration mechanism by oleanolic acid.
AB  - Our study sought to evaluate the anxiolytic and antidepressant activities of
      oleanolic acid as well as the neural mechanisms involved. Animal models such as
      barbiturate sleep-induction, light-dark box, elevated plus maze, forced swimming
      test, tail suspension test and open field test were conducted. Male Albino Swiss
      mice were treated orally with vehicle 10 mL/kg, fluoxetine 20 mg/kg, imipramine
      15 mg/kg, diazepam 1 mg/kg or oleanolic acid 5-40 mg/kg. Pretreatment
      (intraperitoneal) of animals with pentylenetetrazole (PTZ) 20 mg/kg, 1-(2
      methoxyphenyl)-4-[4- (2-phthalimido) butyl]piperazine hydrobromide (NAN-190) 0.5
      mg/kg, p-chlorophenylalanine methyl ester (PCPA) 100 mg/kg or alpha-methyl-p
      tyrosine (AMPT) 100 mg/kg, WAY100635 (WAY) 0.3 mg/kg, prazosin (PRAZ) 1 mg/kg,
      yohimbine 2 mg/kg as well as monoamine oxidase assay and hippocampal brain
      derived neurotrophic factor (BDNF) quantification were carried out. Oleanolic
      acid potentiated the hypnotic effect of barbiturate and demonstrated an
      anxiolytic effect in both the light-dark box and elevated plus maze. This effect
      was not reversed by PTZ. Acute and/or chronic oral treatment of mice with
      oleanolic acid (5-20 mg/kg) elicited an antidepressant effect in the forced
      swimming test and the tail suspension test without interfering with the locomotor
      activity. The antidepressant effect of oleanolic acid was attenuated by NAN-190,
      AMPT, PCPA, WAY and PRAZ. Although monoamine oxidase activity remained unaltered
      by oleanolic acid, chronic administration of oleanolic acid augmented hippocampal
      BDNF level. These findings demonstrate multiple mechanisms of the anxiolytic and
      antidepressant effect of oleanolic acid. 

PMID- 24920138
TI  - A case suspected for yellow fever vaccine-associated viscerotropic disease in the
      Netherlands.
AB  - Yellow fever (YF) 17D vaccine is one of the most successful vaccines ever
      developed. Since 2001, 56 cases of yellow fever vaccine-associated viscerotropic
      disease (YEL-AVD) have been published in the peer-reviewed literature. Here, we
      report a new case suspected for YEL-AVD in the Netherlands. Further research is
      needed to determine the true incidence of YEL-AVD and to clarify host and vaccine
      associated factors in the pathogenesis of YEL-AVD. Because of the potential
      adverse events, healthcare providers should carefully consider vaccination only
      in people who are truly at risk for YF infection, especially in primary vaccine
      recipients. 

PMID- 24920139
TI  - The mammary glands of the Amazonian manatee, Trichechus inunguis (Mammalia:
      Sirenia): morphological characteristics and microscopic anatomy.
AB  - The mammaries from carcasses of two female Amazonian manatees were examined.
      Trichechus inunguis possesses two axillary mammaries beneath the pectoral fins,
      one on each side of the body. Each papilla mammae has a small hole on its apex-
      the ostium papillare. The mammaries are covered by a stratified squamous
      keratinized epithelium. The epithelium of the mammary ducts became thinner more
      deeply in the tissue and varied from stratified to simple cuboidal. There was no
      evidence of glandular activity or secretion into the ducts of the mammary glands.

PMID- 24920135
TI  - Effects of acute alcohol consumption and processing of emotion in faces:
      Implications for understanding alcohol-related aggression.
AB  - The negative consequences of chronic alcohol abuse are well known, but heavy
      episodic consumption ("binge drinking") is also associated with significant
      personal and societal harms. Aggressive tendencies are increased after alcohol
      but the mechanisms underlying these changes are not fully understood. While
      effects on behavioural control are likely to be important, other effects may be
      involved given the widespread action of alcohol. Altered processing of social
      signals is associated with changes in social behaviours, including aggression,
      but until recently there has been little research investigating the effects of
      acute alcohol consumption on these outcomes. Recent work investigating the
      effects of acute alcohol on emotional face processing has suggested reduced
      sensitivity to submissive signals (sad faces) and increased perceptual bias
      towards provocative signals (angry faces) after alcohol consumption, which may
      play a role in alcohol-related aggression. Here we discuss a putative mechanism
      that may explain how alcohol consumption influences emotional processing and
      subsequent aggressive responding, via disruption of orbitofrontal cortex (OFC)
      amygdala connectivity. While the importance of emotional processing on social
      behaviours is well established, research into acute alcohol consumption and
      emotional processing is still in its infancy. Further research is needed and we
      outline a research agenda to address gaps in the literature. 

PMID- 24920140
TI  - [Comparative radiologic examination of the canine elbow with and without elbow
      dysplasia under standardized load].
AB  - OBJECTIVE AND AIM: Application of an X-ray technique under load to determine the
      humeroradial and humeroulnar joint conformation of dogs with elbow dysplasia
      (ED). The aim of the study was to determine whether there are significant
      differences in the measurements of dysplastic joints compared to healthy joints.
      In addition, we formulated the hypothesis, that a differentiation between
      humeroulnar and humeroradial incongruence in dysplastic elbows can be made based
      on the acquired radiographic measurements. MATERIAL AND METHODS: Radiographic
      measurements were obtained in 149 dogs with ED and compared to the results of a
      control group established in a previous study. Based on frequently observed
      measurement variations, these 149 elbow joints were categorized into different
      subgroups, which we re-compared with the control group. In healthy elbow joints
      of euthanized dogs, four different radial and ulnar osteotomies were performed
      with two- and three-dimensional conformation readjustment of the elbow joint. The
      joints were subjected to the same radiographic measurements and the results were
      compared to the control and ED groups. RESULTS: There were no significant
      differences between the control group and all 149 ED joints. However, a marked
      delineation was possible because of significant differences and descriptive
      statistics among the four subgroups of ED joints. One of these subgroups
      displayed significant differences compared to all the examined groups and was
      labeled type I (n = 60). Because of a lack of distinction between two subgroups,
      these were combined and labeled type II (n = 40). Another sub-group comprising
      all the elbows that could not be classified as either type I or type II was
      labeled "indiff" (n = 49). The criteria for assigning an affected elbow joint to
      type I, type II or indiff were three subchondral joint space-widths, three
      indices calculated from the joint space-widths and one angle. CONCLUSION AND
      CLINICAL RELEVANCE: The technique investigated is suitable to assign a great
      number of affected joints to an incongruence type (type I or type II).The results
      of the osteotomy groups provide evidence that the three-dimensional ulnar
      shortening displays similarities to type I, whereas the three-dimensional radius
      shortening shows similarities to type II.

PMID- 24920141
TI  - Sagittal joint instability in the cranial cruciate ligament insufficient canine
      stifle. Caudal slippage of the femur and not cranial tibial subluxation.
AB  - OBJECTIVE: This in vivo study qualitatively describes the sagittal motion pattern
      of the cranial cruciate ligament (CrCL) insufficient canine stifle in operated
      and unoperated joints with cranio-caudal laxity on palpation. MATERIAL AND
      METHODS: Sagittal stifle kinematics were recorded in vivo in dogs (> 15 kg BW)
      with unilateral (n = 7) or bilateral (n = 6) complete CrCL rupture and positive
      cranial drawer test as well as two sound control dogs using uniplanar
      fluoroscopic kinematography with the dogs walking on a treadmill. Stifle
      stability and sagittal motion pattern of the femur and the tibia were determined
      by visual inspection of the fluoroscopic video sequences. RESULTS: Control dogs
      showed no cranio-caudal instability, identical to the contralateral stifles of
      the dogs with unilateral rupture. All unoperated stifles with CrCL rupture (n =
      6) showed caudal slippage of the femur at the beginning of the stance phase. Of
      the 13 operated stifles (TightRope: n = 1, tibial tuberosity advancement, TTA: n
      = 6, tibial plateau leveling osteotomy, TPLO: n = 5, cranial closing wedge
      osteotomy, CCWO: n = 1) nine were unstable, showing the same motion pattern as
      the unoperated stifles. CONCLUSION: In the CrCL insufficient stifle with in vivo
      cranio-caudal instability caudal slippage of the distal femur at tow touch is the
      predominant motion pattern. CLINICAL SIGNIFICANCE: The discrepancy between in
      vivo motion pattern and in vitro simulation of CrCL insufficiency in which
      cranial tibial subluxation is the predominant sagittal motion pattern warrants
      further studies.

PMID- 24920142
TI  - [Quality of life in primary and adjuvant veterinary radiation therapy. An owner
      survey].
AB  - OBJECTIVE: External radiation therapy has been available since 2011 for small
      animals at the University of Munich. The aim of the study was to evaluate the
      quality of life of treated pets and the satisfaction of their owners. MATERIAL
      AND METHODS: The questionnaire was sent to the owners of all the pets (n = 91)
      that had undergone primary or adjuvant radiotherapy at the Clinic of Small Animal
      Medicine, University of Munich, since April 2011. RESULTS: The questionnaire was
      returned by 68 (74.7%) owners. According to their assessment, the quality of life
      improved in 41 cases (60.3%) after treatment where- as in 13 patients (19.1%) a
      decline was described. The majority of owners (88.2%) would have decided for
      repeated radiation therapy. CONCLUSION: Improvement of the animals' quality of
      life is related to a high satisfaction (83.8%) of the owners (p = 0.003) and
      their positive attitude towards radiotherapy (p = 0.027). CLINICAL RELEVANCE:
      Analyses showed that for these owners, the treatment was a worthwhile therapy
      despite it requiring much time and money.

PMID- 24920143
TI  - Efficacy and safety of rush immunotherapy with alum-precipitated allergens in
      canine atopic dermatitis.
AB  - OBJECTIVES: Canine atopic dermatitis is a very common disease in small animal
      practice. Its only specific treatment is allergen immunotherapy. In rush
      immunotherapy (RIT) increasing doses of allergen extract are injected
      subcutaneously in short intervals. Maintenance doses are achieved within one day
      compared to weeks or months with conventional immunotherapy. The aim of this
      study was to evaluate the safety and efficacy of RIT with alum-precipitated
      allergens. MATERIALS AND METHODS: A series of 20 dogs with atopic dermatitis
      underwent RIT with alum-precipitated allergens. Pruritus and medications at the
      start of the immunotherapy and 12 months afterwards were compared and adverse
      effects were recorded. RESULTS: Significant improvement in pruritus (p = 0.0001)
      and medication scores (p = 0.0004) was noted after approximately 12 months of
      treatment. The observed clinical response was good to excellent in 70% of the
      dogs, consistent with other published reports. One dog vomited once during the
      induction day, with no other clinical problems and completion of the normal
      protocol. The other 19 dogs showed no adverse effects at all during or after RIT.
      CONCLUSION AND CLINICAL RELEVANCE: RIT with alum-precipitated allergens seems to
      be a safe and efficacious method to treat dogs with atopic dermatitis.

PMID- 24920144
TI  - [Buccal glucose measurements in dogs using safety lancets for blood sampling].
AB  - OBJECTIVE: Glucose measurements at the pinna or paws are an important part of the
      management of diabetic dogs. Despite extensive rubbing or warming of the testing
      site, an adequate blood sample cannot always be obtained. Therefore, the
      objective of this study was to evaluate the lip as an alternative sampling site
      with respect to practicability and tolerance by the dogs and reliability of the
      measured values. MATERIAL AND METHODS: Nine clinic-owned male-castrated healthy
      beagles were included in this prospective study. Glucose measurements were
      performed using a glucometer developed for veterinary use, before and 15 minutes
      after oral application of glucose syrup. Capillary blood was collected using two
      commercially available safety lancets (Wellion Safety lancet [23 gauge] and
      Wellion Safety lancet special [blade 0.8 mm]) at the buccal mucosa of the upper
      lip and at the pinna. Measured values were compared with those obtained from
      venous plasma (reference method). RESULTS: Buccal glucose measurements were easy
      to perform and were well tolerated by the dogs without obvious pain reactions.
      There was no difference between the glucose concentrations from the lip samples
      and those determined using the reference method (p = 0.793, F < 1). The glucose
      application had no effect on the observed differences (reference value minus
      glucometer value; p = 0.63, F < 1). However, in one dog, a clinically problematic
      discrepancy of 3.6 mmol/l was observed. The special lancet caused noticeable
      secondary bleeding in two dogs. CONCLUSION AND CLINICAL RELEVANCE: The results of
      this study indicate that the buccal mucosa is a convenient and reliable
      alternative sampling site for glucose measurements in dogs. Problematic
      deviations from reference values are possible after oral glucose application and
      the use of blade-like needles is not encouraged.

PMID- 24920145
TI  - [Urethral stent to treat a refractory traumatic urethra stricture in a male
      hunting dog].
AB  - In a 1.5-year-old male hunting dog, a urethral defect distal to the pelvic
      flexure and the resulting urethral fistula were treated with a mucosal graft and
      a transurethral catheter. Six months postoperatively a stricture of the urethra
      occurred. Following balloon dilatation, urination was normal. One month after
      dilatation, urethral narrowing relapsed and was treated using a combination of
      balloon dilatation and urethral stent implantation. Ten months following stent
      implantation the dog continued to show normal urination, although a deformation
      of the proximal part of the stent was diagnosed radiographically. During the 1
      year follow-up no additional complications were observed. In the future, urethral
      stents may replace surgical resection of the narrowed urethral region and re
      anastomosis of the urethra. 

PMID- 24920146
TI  - [Intraocular osteosarcoma in a dog].
AB  - The present case describes the diagnostic and therapeutic procedure of a dog with
      an intraocular osteosarcoma. According to the results of the diagnostic imaging
      studies, the tentative diagnosis of an intraocular neoplasm with perforation of
      the globe and orbital invasion of the tumour was made and an orbital exenteration
      was performed. The histopathological diagnosis of the extracted organ implied an
      intraocular, extraskeletal osteosarcoma. Seventy-seven days later the patient
      displayed an acute paraparesis. Clinical and diagnostic reevaluation using
      magnetic resonance imaging (MRI) was performed and the dog was euthanized at the
      owner's request. By means of MRI and necropsy, an additional axial osteosarcoma
      of the 6th lumbar vertebra and a malignant melanoma of the right tonsil were
      diagnosed. 

PMID- 24920147
TI  - [Treatment of systemic hypertension associated with kidney disease in the dog and
      cat].
AB  - Systemic hypertension is an increasingly diagnosed disorder in dogs and cats and
      frequently occurs secondary to chronic kidney disease. Prevention of damage to
      organs such as the kidneys, brain, heart, and eyes is one of the primary concerns
      in the management of veterinary patients with hypertension. This article reviews
      the guidelines for antihypertensive therapy in patients with, or at risk for,
      kidney disease, including the initiation of treatment and currently recommended
      medications. 

PMID- 24920149
TI  - Function of lateral line canal morphology.
AB  - Fish perceive water motions and pressure gradients with their lateral line.
      Lateral line information is used for prey detection, spatial orientation,
      predator avoidance, schooling behavior, intraspecific communication and station
      holding. The lateral line of most fishes consists of superficial neuromasts (SNs)
      and canal neuromasts (CNs). The distribution of SNs and CNs shows a high degree
      of variation among fishes. Researchers have speculated for decades about the
      functional significance of this diversity, often without any conclusive answers.
      Klein et al. (2013) examined how tubules, pore number and pore patterns affect
      the filter properties of lateral line canals in a marine teleost, the black
      prickleback (Xiphister atropurpureus). A preliminary mathematical model was
      formulated and biomimetic sensors were built. For the present study the
      mathematical model was extended to understand the major underlying principle of
      how canal dimensions influence the filter properties of the lateral line. Both
      the extended mathematical model and the sensor experiments show that the number
      and distribution of pores determine the spatial filter properties of the lateral
      line. In an environment with little hydrodynamic noise, simple and complex
      lateral line canals have comparable response properties. However, if exposed to
      highly turbulent conditions, canals with numerous widely spaced pores increase
      the signal to noise ratio significantly.

PMID- 24920150
TI  - A review of the melatonin functions in zebrafish physiology.
AB  - Melatonin is part of the evolutionary conserved highly functional network in
      vertebrates. It plays a central role in the adaptative behavior of the animal to
      the environment, including entrainment of daily and annual physiological rhythms,
      reproductive behavior, food intake, locomotor activity, growth, and breeding
      performance. In zebrafish, apart from its synchronizing capabilities, melatonin
      seems to have a major role in multiple physiological processes. Extensive
      knowledge of its genome and the identification of a series of genes with the same
      functions as those in humans, the relative ease of obtaining mutants, and the
      similarities between zebrafish and human pathologies make it an excellent
      experimental model organism of human diseases. Moreover, it is a common
      experimental species because of easy handling, breeding, and developmental
      control. Among other pathophysiologies, zebrafish are now used in studies of
      neurodegeneration and neurological diseases, endocrine diseases, behavior,
      muscular dystrophies, developmental alterations, circadian rhythms, and drugs
      screening. The purpose of this review was to update the current knowledge on the
      synthesis and biological functions of melatonin in zebrafish, keeping in mind its
      relevance not only in the physiology of the animal, but also in
      pathophysiological conditions. 

PMID- 24920148
TI  - An exploration of how psychotic-like symptoms are experienced, endorsed, and
      understood from the National Latino and Asian American Study and National Survey
      of American Life.
AB  - OBJECTIVE: . To examine racial-ethnic differences in the endorsement and
      attribution of psychotic-like symptoms in a nationally representative sample of
      African-Americans, Asians, Caribbean Blacks, and Latinos living in the USA.
      DESIGN: Data were drawn from a total of 979 respondents who endorsed psychotic
      like symptoms as part of the National Latino and Asian American Study (NLAAS) and
      the National Survey of American Life (NSAL). We use a mixed qualitative and
      quantitative analytical approach to examine sociodemographic and ethnic
      variations in the prevalence and attributions of hallucinations and other
      psychotic-like symptoms in the NLAAS and NSAL. The lifetime presence of psychotic
      like symptoms was assessed using the World Health Organization Composite
      International Diagnostic Interview (WMH-CIDI) psychotic symptom screener. We used
      logistic regression models to examine the probability of endorsing the four most
      frequently occurring thematic categories for psychotic-like experiences by
      race/ethnicity (n > 100). We used qualitative methods to explore common themes
      from participant responses to open ended questions on their attributions for
      psychotic-like symptoms. RESULTS: African-Americans were significantly less
      likely to endorse visual hallucinations compared to Caribbean Blacks (73.7% and
      89.3%, p < .001), but they endorsed auditory hallucinations symptoms more than
      Caribbean Blacks (43.1% and 25.7, p < .05). Endorsing delusions of reference and
      thought insertion/withdrawal were more prevalent for Latinos than for African
      Americans (11% and 4.7%, p < .05; 6.3% and 2.7%, p < .05, respectively).
      Attribution themes included: supernatural, ghosts/unidentified beings, death and
      dying, spirituality or religiosity, premonitions, familial and other. Respondents
      differed by race/ethnicity in the attributions given to psychotic like symptoms.
      CONCLUSION: Findings suggest that variations exist by race/ethnicity in both
      psychotic-like symptom endorsement and in self-reported
      attributions/understandings for these symptoms on a psychosis screening
      instrument. Ethnic/racial differences could result from culturally sanctioned
      beliefs and idioms of distress that deserve more attention in conducting
      culturally informed and responsive screening, assessment and treatment.

PMID- 24920151
TI  - Head titubation: an unrecognized manifestation of Joubert syndrome and other
      (midline) cerebellar disorders?

PMID- 24920152
TI  - Incomplete duplication of a lower extremity (polymelia): a case report.
AB  - INTRODUCTION: Polymelia, or congenital duplication of a limb, is an extremely
      rare entity in humans, with few cases reported in the literature. CASE
      PRESENTATION: We present the case of a six-month-old Hispanic boy born with a
      lower limb bud on the left posterior thigh. CONCLUSION: The infant had a
      favorable outcome and evolution after surgical treatment of his supernumerary
      limb, with no after-effects or impairment whatsoever.

PMID- 24920153
TI  - Nonlocal and nonlinear electrostatics of a dipolar Coulomb fluid.
AB  - We study a model Coulomb fluid consisting of dipolar solvent molecules of finite
      extent which generalizes the point-like dipolar Poisson-Boltzmann model (DPB)
      previously introduced by Coalson and Duncan (1996 J. Phys. Chem. 100 2612) and
      Abrashkin et al (2007 Phys. Rev. Lett. 99 077801). We formulate a nonlocal
      Poisson-Boltzmann equation (NLPB) and study both linear and nonlinear dielectric
      response in this model for the case of a single plane geometry. Our results shed
      light on the relevance of nonlocal versus nonlinear effects in continuum models
      of material electrostatics. 

PMID- 24920154
TI  - Are we (mis)guided by current guidelines on intrapartum fetal heart rate
      monitoring? Case for a more physiological approach to interpretation.
AB  - Original interpretations of fetal heart rate (FHR) patterns equated FHR
      decelerations with 'fetal distress', requiring expeditious delivery. This
      simplistic interpretation is still implied in our clinical guidelines despite 40
      years of increasing understanding of the behaviour and regulation of the fetal
      cardiovascular system during labour. The physiological basis of FHR responses and
      adaptations to oxygen deprivation is de-emphasised, whilst generations of
      obstetricians and midwives are trained to focus on, and classify, the
      morphological appearances of decelerations into descriptive categories, with no
      attempt to understand how the fetus defends itself and compensates for
      intrapartum hypoxic ischaemic insults, or the patterns that suggest progressive
      loss of compensation. Consequently, there is a lack of confidence, marked
      variation in FHR interpretation, defensive practices, unnecessary operative
      interventions, and a failure to recognise abnormal FHR patterns, resulting in
      adverse outcomes and expensive litigation. 

PMID- 24920155
TI  - Exploring ecotoxicological fish bioassay for the evaluation of uranium
      reprotoxicity.
AB  - Although reproduction in fish is known to be sensitive to metal exposure, few
      ecotoxicological studies have focused on the toxicological effects of metals.
      Because uranium (U) is naturally present in aquatic ecosystems (0.6-2 mg/L),
      freshwater organisms are subjected to chronic U exposure. Although new
      standardized assays are currently being developed to mimic realistic exposure
      conditions, they could be improved by taking into account the contamination that
      occurs throughout the life cycle of fish. The authors initially evaluated the
      effect of food (commercial flakes vs pure Spirulina) and ionic composition of the
      exposure medium on the reproductive performance of Danio rerio. The effects of U
      exposure on reproduction then were assessed 1) for the F0 adult stage at short
      exposure times (5 d, 20 d, and 40 d), and 2) for the F0 stage and the F1
      generation after 200 d of exposure to control, low (20 ug U/L), and moderate (250
      ug U/L) waterborne levels of U. Reproductive endpoints (reproductive success,
      fecundity, number of spawns, egg and larvae viability, and hatching) were
      measured mainly after the first spawn and after 10 d of cumulative spawns. The
      authors evaluated the plasticity of these endpoints and compared the effect of
      exposure conditions to identify the most relevant markers of the effect of U
      exposure on reproductive performance of D. rerio.

PMID- 24920156
TI  - Evaluation of hospital readmissions in surgical patients: do administrative data
      tell the real story?
AB  - IMPORTANCE: The Centers for Medicare & Medicaid Services has developed an all
      cause readmission measure that uses administrative data to measure readmission
      rates and financially penalize hospitals with higher-than-expected readmission
      rates. OBJECTIVES: To examine the accuracy of administrative codes in determining
      the cause of readmission as determined by medical record review, to evaluate the
      readmission measure's ability to accurately identify a readmission as planned,
      and to document the frequency of readmissions for reasons clinically unrelated to
      the original hospital stay. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      review of all consecutive patients discharged from general surgery services at a
      tertiary care, university-affiliated teaching hospital during 8 consecutive
      quarters (quarter 4 [October through December] of 2009 through quarter 3 [July
      through September] of 2011). Clinical readmission diagnosis determined from
      direct medical record review was compared with the administrative diagnosis
      recorded in a claims database. The number of planned hospital readmissions
      defined by the readmission measure was compared with the number identified using
      clinical data. Readmissions unrelated to the original hospital stay were
      identified using clinical data. MAIN OUTCOMES AND MEASURES: Discordance rate
      between administrative and clinical diagnoses for all hospital readmissions,
      discrepancy between planned readmissions defined by the readmission measure and
      identified by clinical medical record review, and fraction of hospital
      readmissions unrelated to the original hospital stay. RESULTS: Of the 315
      hospital readmissions, the readmission diagnosis listed in the administrative
      claims data differed from the clinical diagnosis in 97 readmissions (30.8%). The
      readmission measure identified 15 readmissions (4.8%) as planned, whereas
      clinical data identified 43 readmissions (13.7%) as planned. Unrelated
      readmissions comprised 70 of the 258 unplanned readmissions (27.1%). CONCLUSIONS
      AND RELEVANCE: Administrative billing data, as used by the readmission measure,
      do not reliably describe the reason for readmission. The readmission measure
      accounts for less than half of the planned readmissions and does not account for
      the nearly one-third of readmissions unrelated to the original hospital stay.
      Implementation of this readmission measure may result in unwarranted financial
      penalties for hospitals.

PMID- 24920157
TI  - Feeling connected to younger versus older selves: the asymmetric impact of life
      stage orientation.
AB  - The concept of life-stage orientation is proposed. Youth is a period of time
      characterised by strong feelings and emotions, but weak reasoning and cognitive
      skill. Conversely, adulthood is characterised by strong rationality, but weak
      emotionality. Two studies revealed that merely bringing these concepts to mind
      changes real-time feelings and behaviour. Participants who were instructed to act
      like their "adult" selves exhibited greater self-control in a cold pressor test
      than control participants and those who acted like their "youth" selves
      (Experiment 1). However, being induced to feel connected to youth enhanced
      enjoyment for fun videos (Experiment 2). Hence, the extent to which people are
      oriented towards youth versus adulthood has asymmetric costs and benefits for the
      present. Connecting to youth boosts experiential capacities (in this case,
      enjoying oneself) at the cost of agency, whereas connecting to adulthood boosts
      agentic capacities (in this case, exerting will-power) at the cost of experience.

PMID- 24920158
TI  - Fractal dimension analysis of malignant and benign endobronchial ultrasound
      nodes.
AB  - BACKGROUND: Endobronchial ultrasonography (EBUS) has been applied as a routine
      procedure for the diagnostic of hiliar and mediastinal nodes. The authors
      assessed the relationship between the echographic appearance of mediastinal
      nodes, based on endobronchial ultrasound images, and the likelihood of
      malignancy. METHODS: The images of twelve malignant and eleven benign nodes were
      evaluated. A previous processing method was applied to improve the quality of the
      images and to enhance the details. Texture and morphology parameters analyzed
      were: the image texture of the echographies and a fractal dimension that
      expressed the relationship between area and perimeter of the structures that
      appear in the image, and characterizes the convoluted inner structure of the
      hiliar and mediastinal nodes. RESULTS: Processed images showed that relationship
      between log perimeter and log area of hilar nodes was lineal (i.e. perimeter vs.
      area follow a power law). Fractal dimension was lower in the malignant nodes
      compared with non-malignant nodes (1.47(0.09), 1.53(0.10) mean(SD), Mann-Whitney
      U test p < 0.05)). CONCLUSION: Fractal dimension of ultrasonographic images of
      mediastinal nodes obtained through endobronchial ultrasound differ in malignant
      nodes from non-malignant. This parameter could differentiate malignat and non
      malignat mediastinic and hiliar nodes.

PMID- 24920159
TI  - Probing phosphorylation-dependent protein interactions within functional domains
      of histone deacetylase 5 (HDAC5).
AB  - Class IIa histone deacetylases (HDACs) are critical transcriptional regulators,
      shuttling between nuclear and cytoplasmic cellular compartments. Within the
      nucleus, these HDACs repress transcription as components of multiprotein
      complexes, such as the nuclear corepressor and beclin-6 corepressor (BCoR)
      complexes. Cytoplasmic relocalization relieves this transcriptional repressive
      function. Class IIa HDAC shuttling is controlled, in part, by phosphorylations
      flanking the nuclear localization signal (NLS). Furthermore, we have reported
      that phosphorylation within the NLS by the kinase Aurora B modulates the
      localization and function of the class IIa HDAC5 during mitosis. While we
      identified numerous additional HDAC5 phosphorylations, their regulatory functions
      remain unknown. Here, we studied phosphorylation sites within functional HDAC5
      domains, including the deacetylation domain (DAC, Ser755), nuclear export signal
      (NES, Ser1108), and an acidic domain (AD, Ser611). We have generated
      phosphomutant cell lines to investigate how absence of phosphorylation at these
      sites impacts HDAC5 localization, enzymatic activity, and protein interactions.
      Combining molecular biology and quantitative MS, we have defined the interactions
      and HDAC5-containing complexes mediated by site-specific phosphorylation and
      quantified selected changes using parallel reaction monitoring. These results
      expand the current understanding of HDAC regulation, and the functions of this
      critical family of proteins within human cells.

PMID- 24920160
TI  - Granulocyte colony-stimulating factor does not promote neurogenesis after
      experimental intracerebral haemorrhage.
AB  - BACKGROUND: Hematopoietic growth factors have been suggested to induce
      neuroprotective and regenerative effects in various animal models of cerebral
      injury. However, the pathways involved remain widely unexplored. AIMS: This study
      aimed to investigate effects of local and systemic administration of granulocyte
      colony-stimulating factor on brain damage, functional recovery, and cerebral
      neurogenesis in an intracerebral haemorrhage whole blood injection model in rats.
      METHODS: Eight-week-old male Wistar rats (n = 100) underwent induction of
      striatal intracerebral haemorrhage by autologous whole blood injection or sham
      procedure and were randomly assigned to either (a) systemic treatment with
      granulocyte colony-stimulating factor (60 MUg/kg) for five-days; (b) single
      intracerebral injection of granulocyte colony-stimulating factor (60 MUg/kg) into
      the cavity; or (c) application of vehicle for five-days. Bromodeoxyuridine
      labelling and immunohistochemistry were used to analyze proliferation and
      survival of newly born cells in the sub-ventricular zone and the hippocampal
      dentate gyrus. Moreover, functional deficits and lesion volume were assessed
      until day 42 after intracerebral haemorrhage. RESULTS: Differences in lesion size
      or hemispheric atrophy between granulocyte colony-stimulating factor-treated and
      control groups did not reach statistical significance. Neither systemic, nor
      local granulocyte colony-stimulating factor administration induced neurogenesis
      within the dentate gyrus or the sub-ventricular zone. The survival of newborn
      cells in these regions was prevented by intracerebral granulocyte colony
      stimulating factor application. A subtle benefit in functional recovery at day 14
      after intracerebral haemorrhage induction was observed after granulocyte colony
      stimulating factor treatment. CONCLUSION: There was a lack of neuroprotective or
      neuroregenerative effects of granulocyte colony-stimulating factor in the present
      rodent model of intracerebral haemorrhage. Conflicting results from functional
      outcome assessment require further research.

PMID- 24920162
TI  - Cold denaturation of alpha-synuclein amyloid fibrils.
AB  - Although amyloid fibrils are associated with numerous pathologies, their
      conformational stability remains largely unclear. Herein, we probe the thermal
      stability of various amyloid fibrils. alpha-Synuclein fibrils cold-denatured to
      monomers at 0-20  degrees C and heat-denatured at 60-110  degrees C. Meanwhile,
      the fibrils of beta2-microglobulin, Alzheimer's Abeta1-40/Abeta1-42 peptides, and
      insulin exhibited only heat denaturation, although they showed a decrease in
      stability at low temperature. A comparison of structural parameters with positive
      enthalpy and heat capacity changes which showed opposite signs to protein folding
      suggested that the burial of charged residues in fibril cores contributed to the
      cold denaturation of alpha-synuclein fibrils. We propose that although cold
      denaturation is common to both native proteins and misfolded fibrillar states,
      the main-chain dominated amyloid structures may explain amyloid-specific cold
      denaturation arising from the unfavorable burial of charged side-chains in fibril
      cores. 

PMID- 24920161
TI  - Phosphoproteomic approach to characterize protein mono- and poly(ADP
      ribosyl)ation sites from cells.
AB  - Poly(ADP-ribose), or PAR, is a cellular polymer implicated in DNA/RNA metabolism,
      cell death, and cellular stress response via its role as a post-translational
      modification, signaling molecule, and scaffolding element. PAR is synthesized by
      a family of proteins known as poly(ADP-ribose) polymerases, or PARPs, which
      attach PAR polymers to various amino acids of substrate proteins. The nature of
      these polymers (large, charged, heterogeneous, base-labile) has made these
      attachment sites difficult to study by mass spectrometry. Here we propose a new
      pipeline that allows for the identification of mono(ADP-ribosyl)ation and
      poly(ADP-ribosyl)ation sites via the enzymatic product of phosphodiesterase
      treated ADP-ribose, or phospho(ribose). The power of this method lies in the
      enrichment potential of phospho(ribose), which we show to be enriched by
      phosphoproteomic techniques when a neutral buffer, which allows for retention of
      the base-labile attachment site, is used for elution. Through the identification
      of PARP-1 in vitro automodification sites as well as endogenous ADP-ribosylation
      sites from whole cells, we have shown that ADP-ribose can exist on adjacent amino
      acid residues as well as both lysine and arginine in addition to known acidic
      modification sites. The universality of this technique has allowed us to show
      that enrichment of ADP-ribosylated proteins by macrodomain leads to a bias
      against ADP-ribose modifications conjugated to glutamic acids, suggesting that
      the macrodomain is either removing or selecting against these distinct protein
      attachments. Ultimately, the enrichment pipeline presented here offers a
      universal approach for characterizing the mono- and poly(ADP-ribosyl)ated
      proteome. 

PMID- 24920163
TI  - Effect of cation on diffusion coefficient of ionic liquids at onion-like carbon
      electrodes.
AB  - While most supercapacitors are limited in their performance by the stability of
      the electrolyte, using neat ionic liquids (ILs) as the electrolyte can expand the
      voltage window and temperature range of operation. In this study, ILs with
      bis(trifluoromethylsulfonyl)imide (Tf2N) as the anion were investigated as the
      electrolyte in onion-like carbon-based electrochemical capacitors. To probe the
      influence of cations on the electrochemical performance of supercapacitors, three
      different cations were used: 1-ethyl-3-methylimidazolium, 1-hexyl-3
      methylimidazolium and 1,6-bis(3-methylimidazolium-1-yl). A series of
      electrochemical characterization tests was performed using cyclic voltammetry
      (CV), galvanostatic cycling and electrochemical impedance spectroscopy (EIS).
      Diffusion coefficients were measured using EIS and correlated with quasielastic
      neutron scattering and molecular dynamics simulation. These three techniques were
      used in parallel to confirm a consistent trend between the three ILs. It was
      found that the IL with the smaller sized cation had a larger diffusion
      coefficient, leading to a higher capacitance at faster charge-discharge rates.
      Furthermore, the IL electrolyte performance was correlated with increasing
      temperature, which limited the voltage stability window and led to the formation
      of a solid electrolyte interphase on the carbon electrode surface, evident in
      both the CV and EIS experiments. 

PMID- 24920164
TI  - Hydrophobic modification of Pd/SiO2 @single-site mesoporous silicas by
      triethoxyfluorosilane: enhanced catalytic activity and selectivity for one-pot
      oxidation.
AB  - To enhance the catalytic activity in a selective one-pot oxidation using in-situ
      generated H(2)O(2), a hydrophobically modified core-shell catalyst was
      synthesized by means of a simple silylation reaction using the fluorine
      containing silylation agent triethoxyfluorosilane (TEFS, SiF(OEt)(3)). The
      catalyst consisted of a Pd-supported silica nanosphere and a mesoporous silica
      shell containing isolated Ti(IV) and F ions bonded with silicon (Si?F bond).
      Structural analyses using XRD and N(2) adsorption-desorption suggested that the
      mesoporous structure and large surface area of the mesoporous shells were
      retained even after the modification. During the one-pot oxidation of sulfide,
      catalytic activity was enhanced significantly by increasing the amount of
      fluorine in the shell. A hydrophobic surface enhanced adsorption of the
      hydrophobic reactant into the mesopore, while the less hydrophobic oxygenated
      products efficiently diffused into the outside of the shell, which improved the
      catalytic activity and selectivity. In addition, the present methodology can be
      used to enhance the catalytic activity and selectivity in the one-pot oxidation
      of cyclohexane by using an Fe-based core-shell catalytic system.

PMID- 24920165
TI  - C60 molecules grown on a Si-supported nanoporous supramolecular network: a DFT
      study.
AB  - C60 fullerene assemblies on surfaces have attracted considerable attention
      because of their remarkable electronic properties. Now because of the competition
      between the molecules-substrate and the molecule-molecule interactions, an
      ordered C60 array is rather difficult to obtain on silicon surfaces. Here we
      present density functional theory simulations on C60 molecules deposited on a TBB
      (1,3,5-tri(1'-bromophenyl)benzene) monolayer lying on the Si(111)-boron surface
      (denoted SiB). The C60 molecules are located in the nanopores formed by the TBB
      network. Adsorption energy calculations show that the SiB surface governs the C60
      vertical position, whereas the TBB network imposes the C60 lateral position, and
      stabilizes the molecule as well. The low charge density between the C60 and the
      SiB substrate on one hand, and on the other hand between the C60 and the TBB
      molecules, indicates that no covalent bond is formed between the C60 and its
      environment. However, according to charge density differences, a drastic charge
      reorganisation takes place between the Si adatoms and the C60 molecule, but also
      between the C60 and the surrounding TBB molecules. Finally, calculations show
      that a C60 array sandwiched between two TBB molecular layers is stable, which
      opens up the way to the growth of 3D supramolecular networks. 

PMID- 24920166
TI  - The clock drawing test, mortality, incident cardiovascular events and dementia.
AB  - OBJECTIVE: The purpose of this study is to examine the association of the clock
      drawing test (CDT) with incident dementia, cardiovascular events and mortality in
      very elderly hypertensive patients. METHOD: All participants were hypertensive
      and aged 80 years and over. The CDT was administered at baseline and annually
      thereafter. Data on incident cardiovascular, fatal events and dementia were
      collected over follow-up. RESULTS: There were 3845 participants recruited and
      followed up for a mean of 2.1 years. Of these, 2701 completed a CDT with 2259
      available at baseline. Of this group, 6.6% had a cardiovascular event, 6.1% died,
      and 10% were diagnosed with dementia. There was no relationship between baseline
      CDT score and subsequent cardiovascular events or mortality. For incident
      dementia, the hazard ratio was 0.88 (95% confidence intervals 0.83-0.94)
      suggesting that better performance on the baseline CDT was associated with a
      lower risk of dementia. CONCLUSION: These results provide tentative support for
      the CDT alongside other cognitive screening tools in a hypertensive elderly
      population.

PMID- 24920167
TI  - Association of EMP1 with gastric carcinoma invasion, survival and prognosis.
AB  - The aim of this study was to determine the expression and function of epithelial
      membrane protein 1 (EMP1) in gastric carcinoma. Gastric samples were taken from
      cancer lesions and adjacent normal tissue in gastric cancer patients immediately
      after endoscopic biopsy. A portion of the sample was either fixed in 4%
      paraformaldehyde and embedded in paraffin for immunohistochemistry or stored in
      liquid nitrogen for western blotting. In order to determine protein expression of
      EMP1 in gastric cancer (n=65) and normal tissue (n=27), semi-quantitative
      immunohistochemistry and western blotting were utilized. For in vitro studies,
      the human gastric cancer cell line SGC-7901 was maintained in RPMI-1640 medium
      supplemented with 10% fetal bovine serum. Recombinant lentivirus mediated
      overexpression of EMP1 in SGC-7901 cells was quantified with quantitative
      polymerase chain reaction (qPCR) and western blotting. Control SGC-7901 cells
      were transfected with an empty vector. To further study the effect of EMP1
      overexpression in SGC-7901 cells, cell proliferation, cell apoptosis and
      migration and invasion assays were conducted. The expression of EMP1 was
      significantly lower in gastric cancer tissue compared to normal tissue using both
      immunohistochemistry (41.5 vs. 70.4% of tissues, P<0.05) and western blotting
      (0.153 +/- 0.012 vs. 0.626 +/- 0.058, P<0.05). Decreased expression of EMP1 was
      significantly correlated with tumor invasion, lymph node metastasis, clinical
      stage and histological grade of patients with gastric cancer (P<0.05). According
      to Kaplan-Meier analysis, low EMP1 expression correlated significantly with poor
      overall 5-year survival (47.4 vs. 70.3% survival, P<0.05). SGC-7901 cells
      transfected with EMP1 had a lower survival fraction, higher cell apoptosis (13.2
      +/- 1.5% vs. 2.2 +/- 0.5%, P<0.05), significant decrease in migration and
      invasion (157.0 +/- 16.0 and 112.0 +/- 12.0, respectively vs. 243.0 +/- 21.0 and
      203.0 +/- 19.0, respectively, P<0.05), higher caspase-9 (0.501 +/- 0.050 vs.
      0.114 +/- 0.010, P<0.05) and lower VEGFC protein expression 0.135 +/- 0.011 vs.
      0.619 +/- 0.074, P<0.05) relative to cells not transfected with EMP1. Low EMP1
      expression in gastric cancer is associated with increased disease severity,
      suggesting that EMP1 may be a negative regulator of gastric cancer.

PMID- 24920168
TI  - Characterization of the Blastocystis-specific faecal IgA immune response in pigs.
AB  - Blastocystis is an intestinal protist found in many species including humans and
      pigs. It has a controversial pathogenesis and has been implicated as a potential
      cause of irritable bowel syndrome. Our previous studies identified pigs as
      potential animal models for blastocystosis by demonstrating that they were likely
      natural hosts of Blastocystis and can harbour subtypes (ST) in common with
      humans. Furthermore, our finding of a lack of intestinal histopathology
      associated with Blastocystis infection in pigs is also a consistent finding in
      examined infected humans. In this study, we aimed to identify and characterize
      the Blastocystis-specific mucosal IgA response in pigs by immunoblotting, using
      pig faecal antibodies and Blastocystis antigen. Faeces from 233 pigs representing
      three age groups (sows/boars, growers/weaners and piglets) and including five
      dexamethasone-immunosuppressed research pigs were tested. The majority (81.5%) of
      the pigs had faecal IgA reactivity against Blastocystis proteins of molecular
      weights of 17.5-120 kDa. Reactivity to a >250 kDa protein was found in 18.5% of
      pigs. Notably, immunosuppressed pigs and piglets were statistically more likely
      to have reactivity to this protein compared to growers/weaners and sows/boars,
      respectively. These results corroborate other findings suggesting that
      compromised immunity may predispose to blastocystosis and support our contention
      that pigs are potentially good models for pathogenesis studies.

PMID- 24920169
TI  - Gastrointestinal toxicity after vincristine or cyclophosphamide administered with
      or without maropitant in dogs: a prospective randomised controlled study.
AB  - OBJECTIVES: To assess the prevalence of gastrointestinal toxicity in dogs
      receiving chemotherapy with vincristine and cyclophosphamide and the efficacy of
      maropitant citrate (CereniaTM, Zoetis) in reducing these events. METHODS: Dogs
      receiving chemotherapy with cyclophosphamide or vincristine were randomised to
      either receive maropitant or not in the period immediately after treatment and
      for 4 days afterwards. Owners completed a diary of adverse events following
      treatment. RESULTS: Adverse events occurred in 40/58 (69%) dogs in the
      vincristine group. Most of these adverse events were mild and included: lethargy
      (62%), appetite loss (43%), diarrhoea (34%) and vomiting (24%). Adverse events
      occurred in 34/42 (81%) dogs treated with cyclophosphamide. Most of these adverse
      events were mild and included: lethargy (62%), diarrhoea (36%), appetite loss
      (36%) and vomiting (21%). There was no difference in total clinical score,
      vomiting, diarrhoea, appetite loss or lethargy score between dogs treated with
      maropitant and non-treated dogs in either the vincristine or cyclophosphamide
      groups. CLINICAL SIGNIFICANCE: Chemotherapy-related side effects are frequent but
      usually mild in dogs receiving vincristine or cyclophosphamide. Prophylactic
      administration of maropitant does not reduce the frequency of adverse events and
      maropitant should be administered only as required for individual cases.

PMID- 24920170
TI  - Physiological and transcriptomic analyses of the thermophilic, aceticlastic
      methanogen Methanosaeta thermophila responding to ammonia stress.
AB  - The inhibitory effects of ammonia on two different degradation pathways of
      methanogenic acetate were evaluated using a pure culture (Methanosaeta
      thermophila strain PT) and defined co-culture (Methanothermobacter
      thermautotrophicus strain TM and Thermacetogenium phaeum strain PB), which
      represented aceticlastic and syntrophic methanogenesis, respectively. Growth
      experiments with high concentrations of ammonia clearly demonstrated that
      sensitivity to ammonia stress was markedly higher in M. thermophila PT than in
      the syntrophic co-culture. M. thermophila PT also exhibited higher sensitivity to
      high pH stress, which indicated that an inability to maintain pH homeostasis is
      an underlying cause of ammonia inhibition. Methanogenesis was inhibited in the
      resting cells of M. thermophila PT with moderate concentrations of ammonia,
      suggesting that the inhibition of enzymes involved in methanogenesis may be one
      of the major factors responsible for ammonia toxicity. Transcriptomic analysis
      revealed a broad range of disturbances in M. thermophila PT cells under ammonia
      stress conditions, including protein denaturation, oxidative stress, and
      intracellular cation imbalances. The results of the present study clearly
      demonstrated that syntrophic acetate degradation dominated over aceticlastic
      methanogenesis under ammonia stress conditions, which is consistent with the
      findings of previous studies on complex microbial community systems. Our results
      also imply that the co-existence of multiple metabolic pathways and their
      different sensitivities to stress factors confer resiliency on methanogenic
      processes. 

PMID- 24920171
TI  - Suppressive potential of Paenibacillus strains isolated from the tomato
      phyllosphere against fusarium crown and root rot of tomato.
AB  - The suppressive potentials of Bacillus and Paenibacillus strains isolated from
      the tomato phyllosphere were investigated to obtain new biocontrol candidates
      against Fusarium crown and root rot of tomato. The suppressive activities of 20
      bacterial strains belonging to these genera were examined using seedlings and
      potted tomato plants, and two Paenibacillus strains (12HD2 and 42NP7) were
      selected as biocontrol candidates against the disease. These two strains
      suppressed the disease in the field experiment. Scanning electron microscopy
      revealed that the treated bacterial cells colonized the root surface, and when
      the roots of the seedlings were treated with strain 42NP7 cells, the cell
      population was maintained on the roots for at least for 4 weeks. Although the
      bacterial strains had no direct antifungal activity against the causal pathogen
      in vitro, an increase was observed in the antifungal activities of acetone
      extracts from tomato roots treated with the cells of both bacterial strains.
      Furthermore, RT-PCR analysis verified that the expression of defense-related
      genes was induced in both the roots and leaves of seedlings treated with the
      bacterial cells. Thus, the root-colonized cells of the two Paenibacillus strains
      were considered to induce resistance in tomato plants, which resulted in the
      suppression of the disease. 

PMID- 24920172
TI  - Ventilation strategies and indoor particulate matter in a classroom.
AB  - Particle mass and number concentrations were measured in a mechanically
      ventilated classroom as part of a study of ventilation strategies for energy
      conservation. The ventilation system was operated either continuously,
      intermittently, or shut down during nights while it was on during workdays. It
      appears that the nighttime ventilation scheme is not important for indoor
      particle concentrations the following day if fans are operated to give five air
      exchanges in advance of the workday. The highest concentrations of PM10 were
      found during and after workdays and were due to human activity in the classroom.
      The average workday PM10 concentration was 14 MUg/m(3) , well below the WHO
      guideline values. The number concentration of particles with diameter <0.750 MUm
      was typically between 0.5 * 10(3) and 3.5 * 10(3)  particle/cm(3) . These
      concentrations were largely independent of the occupants. Transient formation of
      small particles was observed when ventilation was shut down. Then remaining ozone
      reacted with terpenes emitted by indoor sources and gave up to 8 * 10(3) 
      particle/cm(3) before formation stopped due to lack of ozone. The intermittent
      ventilation regime was found least favorable for the indoor air quality in the
      classroom. 

PMID- 24920173
TI  - An integrated artificial photosynthesis system based on peptide nanotubes.
AB  - A peptide nanotube platform that integrates both light-harvesting and catalytic
      units was successfully engineered for artificial photosynthesis. Peptide
      nanotubes not only serve as a hub for physically combining both units, but also
      work as mediators that transfer the energy from photo-excited chromophores to
      catalytic centers. The direct conversion of NAD(+) to NADH upon light
      illumination was demonstrated. This represents a promising step towards efficient
      and fully integrated artificial photosynthesis systems. 

PMID- 24920174
TI  - Overexpression of peroxiredoxin 2 inhibits TGF-beta1-induced epithelial
      mesenchymal transition and cell migration in colorectal cancer.
AB  - Although human peroxiredoxin 2 (PRDX2) has been implicated in tumor progression
      (e.g., invasion and metastasis), little is known regarding its role in the
      epithelial-mesenchymal transition (EMT) process during tumorigenesis. The present
      study offers the first evidence, to the best of our knowledge, that the
      antioxidant enzyme PRDX2 has an important role in regulating the EMT process. It
      was demonstrated that overexpression of PRDX2 leads to changes in cell morphology
      in vitro and potent inhibition of the transforming growth factor (TGF)-beta1
      induced EMT and cell migration of colorectal cancer (CRC) cells. Furthermore,
      PRDX2 regulates the expression of EMT markers, EMT-related transcription factors
      and metastasis-related factors in CRC cells. These results provide new insight
      into the role of PRDX2 in regulating EMT, cell migration and metastasis of CRC
      cells. It was concluded that the upregulation of PRDX2 may be correlated with EMT
      and contributes to the pathogenesis of CRC by inhibiting EMT, cell migration and
      metastasis. Taken together, these findings suggest that PRDX2 may be a key
      regulator of invasion and metastasis by inhibiting EMT of CRC cells, and also
      identifies a therapeutic strategy to effectively decrease the lethality of highly
      malignant types of CRC. 

PMID- 24920176
TI  - Abstracts of the AAGBI GAT Annual Scientific Meeting, 11-13 June 2014, Newcastle,
      UK.

PMID- 24920175
TI  - Knee power is an important parameter in understanding medial knee joint load in
      knee osteoarthritis.
AB  - OBJECTIVE: To determine the extent to which knee extensor strength and power
      explain variance in knee adduction moment (KAM) peak and impulse in clinical knee
      osteoarthritis (OA). METHODS: Fifty-three adults (mean +/- SD age 61.6 +/- 6.3
      years, 11 men) with clinical knee OA participated. The KAM waveform was
      calculated from motion and force data and ensemble averaged from 5 walking
      trials. The KAM peak was normalized to body mass (Nm/kg). The mean KAM impulse
      reflected the mean total medial knee load during stride (Nm * seconds). For
      strength, the maximum knee extensor moment attained from maximal voluntary
      isometric contractions (MVIC) was normalized to body mass (Nm/kg). For power, the
      maximum knee extensor power during isotonic contractions, with the resistance set
      at 25% of MVIC, was normalized to body mass (W/kg). Covariates included age, sex,
      knee pain on the Knee Injury and Osteoarthritis Outcome Score, gait speed, and
      body mass index (BMI). Relationships of the KAM peak and impulse with strength
      and power were examined using sequential stepwise forward linear regressions.
      RESULTS: Covariates did not explain variance in the KAM peak. While extensor
      strength did not, peak knee extensor power explained 8% of the variance in the
      KAM peak (P = 0.02). Sex and BMI explained 24% of the variance in the KAM impulse
      (P < 0.05). Sex, BMI, and knee extensor power explained 31% of the variance in
      the KAM impulse (P = 0.02), with power contributing 7% (P < 0.05). CONCLUSION:
      Knee extensor power was more important than isometric knee strength in
      understanding medial knee loads during gait.

PMID- 24920177
TI  - Palladium-catalyzed direct C2 arylation of N-substituted indoles with 1
      aryltriazenes.
AB  - A novel and efficient palladium-catalyzed C2 arylation of N-substituted indoles
      with 1-aryltriazenes for the synthesis of 2-arylindoles was developed. In the
      presence of BF3?OEt2 and palladium(II) acetate (Pd(OAc)2), N-substituted indoles
      reacted with 1-aryltriazenes in N,N-dimethylacetamide (DMAC) to afford the
      corresponding aryl-indole-type products in good to excellent yields.

PMID- 24920178
TI  - Competition and cooperation between active intra-network and passive extra
      network transport processes.
AB  - Many networks are embedded in physical space and often interact with it. This
      interaction can be exemplified through constraints exerted on network topology,
      or through interactions of processes defined on a network with those that are
      linked to the space that the network is embedded within, leading to complex
      dynamics. Here we discuss an example of such an interaction in which a signaling
      agent is actively transported through the network edges and, at the same time,
      spreads passively through space due to diffusion. We show that these two
      processes cooperate or compete depending on the network topology leading to
      complex dynamics. 

PMID- 24920181
TI  - Female autonomy and reported abortion-seeking in Ghana, West Africa.
AB  - OBJECTIVE: To investigate factors associated with self-reported pregnancy
      termination in Ghana and thereby appreciate the correlates of abortion-seeking in
      order to understand safe abortion care provision. METHODS: In a retrospective
      study, data from the Ghana 2008 Demographic and Health Survey were used to
      investigate factors associated with self-reported pregnancy termination.
      Variables on an individual and household level were examined by both bivariate
      analyses and multivariate logistic regression. A five-point autonomy scale was
      created to explore the role of female autonomy in reported abortion-seeking
      behavior. RESULTS: Among 4916 women included in the survey, 791 (16.1%) reported
      having an abortion. Factors associated with abortion-seeking included being
      older, having attended school, and living in an urban versus a rural area. When
      entered into a logistic regression model with demographic control variables,
      every step up the autonomy scale (i.e. increasing autonomy) was associated with a
      14.0% increased likelihood of reporting the termination of a pregnancy (P <
      0.05). CONCLUSION: Although health system barriers might play a role in
      preventing women from seeking safe abortion services, autonomy on an individual
      level is also important and needs to be addressed if women are to be empowered to
      seek safe abortion services.

PMID- 24920182
TI  - Probing lung microstructure with hyperpolarized 3He gradient echo MRI.
AB  - In this paper we demonstrate that gradient echo MRI with hyperpolarized (3)He gas
      can be used for simultaneously extracting in vivo information about lung
      ventilation properties, alveolar geometrical parameters, and blood vessel network
      structure. This new approach is based on multi-gradient-echo experimental
      measurements of hyperpolarized (3)He gas MRI signal from human lungs and a
      proposed theoretical model of this signal. Based on computer simulations of (3)He
      atoms diffusing in the acinar airway tree in the presence of an inhomogeneous
      magnetic field induced by the susceptibility differences between lung tissue
      (alveolar septa, blood vessels) and lung airspaces, we derive analytical
      expressions relating the time-dependent MR signal to the geometrical parameters
      of acinar airways and the blood vessel network. Data obtained on eight healthy
      volunteers are in good agreement with literature values. This information is
      complementary to the information obtained by means of the in vivo lung
      morphometry technique with hyperpolarized 3He diffusion MRI previously developed
      by our group, and opens new opportunities to study lung microstructure in health
      and disease.

PMID- 24920183
TI  - Evaluation of In-Stent Restenosis After Stent Implantation in the Vertebral
      Artery Ostium by Multislice Computed Tomography Angiography: Factors Affecting
      Accurate Diagnosis.
AB  - PURPOSE: Few articles have evaluated vertebral artery ostium stents using
      multislice computed tomography (CT). The purpose of our study was to evaluate the
      diagnostic performance of 64- and 16-slice CT for detecting significant in-stent
      restenosis after vertebral artery ostium stenting, and to identify factors
      affecting the accurate diagnosis by CT. METHODS: We reviewed 57 stents scanned
      using 64-slice CT and 34 stents using 16-slice CT. The accuracy of CT for
      diagnosing significant in-stent restenosis (>= 50% diameter narrowing) was
      calculated using conventional angiography as a reference standard. Possible
      factors influencing the diagnostic performance of CT were analyzed, such as CT
      scanner, image quality, and stent characteristics. RESULTS: With 64-slice CT, 46
      (80.7%) of 57 stents were classified as evaluable, while with 16-slice CT, 28
      (82.3%) of 34 stents were classified as evaluable. No stents with diameters <=
      2.75 mm were evaluable. The respective results for 64- versus 16-slice CT were
      sensitivity 87.5% (95% confidence interval [CI] 47.3-99.7%) versus 100% (95% CI
      15.8-100.0%), specificity 94.7% (95% CI 82.3%-99.4%) versus 96.2% (95% CI 80.4
      99.9%). Factors reducing the accurate diagnosis were those associated with poor
      image quality, a diameter <= 2.75 mm, and drug-eluting stent type (p < 0.05).
      CONCLUSIONS: 64-slice and 16-slice CT scans are adequate in stents with diameters
      > 2.75 mm for the evaluation of in-stent restenosis after stent implantation in
      the vertebral artery ostium.

PMID- 24920184
TI  - The Value of syngo DynaPBV Neuro During Neuro-Interventional Hypotensive Balloon
      Occlusion Test.
AB  - AIM: This study explored the value of flat detector computed tomography based
      brain perfusion imaging in assessing patient's tolerance prior to the permanent
      internal carotid artery occlusion. MATERIALS AND METHODS: Ten patients diagnosed
      with neurovascular diseases through digital subtracted angiography (DSA) were
      enrolled into this study. Temporary balloon occlusion test (BOT) was performed
      for each patient with hypotensive challenge. During the test, parametric color
      coded quantitative DSA (CCQ-DSA) was generated to evaluate the venous filling
      symmetry on both hemispheres. In addition, cerebral blood volume (CBV) maps were
      acquired before and during the test. Regions of interests were defined to
      quantitatively extract CBV value from affected and unaffected hemispheres and
      calculate relative CBV (rCBV), indicating perfusion symmetry. RESULTS: All the
      patients showed good perfusion symmetry before the test with rCBV close to 1.00.
      During the test, good perfusion symmetry was detected in 7 patients with averaged
      rCBV 1.03 +/- 0.06. Only short venous delay and no ischemic complications were
      recognized. One patient had neither neurologic deficits nor long venous delay
      detected, however, showed hyper-perfusion in specific regions in the CBV maps.
      Two patients failed to pass the test, which showed significantly low CBV value
      from the affected hemisphere with maximum rCBV reduction close to 45%.
      CONCLUSION: CBV map had in general good consistency with clinical manifestations
      as well as venous filling in the BOT. Besides, it may provide further evidence of
      hemodynamic variations and delayed ischemic complications, and thus, had a
      potential to reduce risks and increase treatment safety.

PMID- 24920185
TI  - Perceived discrimination and chronic health in adults from nine ethnic subgroups
      in the USA.
AB  - OBJECTIVE: This comparative analysis examines the association between chronic
      cardiovascular, respiratory and pain conditions, race, ethnicity, nativity,
      length of residency, and perceived discrimination among three racial and nine
      ethnic subgroups of Asian Americans (Vietnamese, Filipino, and Chinese), Latino
      American (Cuban, Portuguese, and Mexican), and Afro-Caribbean American (Haitian,
      Jamaican, and Trinidadian/Tobagonian) respondents. DESIGN: Analysis used weighted
      Collaborative Psychiatric Epidemiology Surveys-merged data from the National
      Latino and Asian American Study and the National Survey of American Life.
      Logistic regression analysis was conducted to determine which groups within the
      model were more likely to report perceived discrimination effects. RESULTS: Afro
      Caribbean subgroups were more likely to report perceived discrimination than
      Asian American and Latino-American subgroups were. Logistic regression revealed a
      significant positive association with perceived discrimination and chronic pain
      only for Latino-American respondents. CONCLUSION: Significant differences in
      reports of perceived discrimination emerged by race and ethnicity. Caribbean
      respondents were more likely to report high levels of perceived discrimination;
      however, they showed fewer significant associations related to chronic health
      conditions compared to Asian Americans and Latino-Americans. Examination of
      perceived discrimination across ethnic subgroups reveals large variations in the
      relationship between chronic health and discrimination by race and ethnicity.
      Examining perceived discrimination by ethnicity may reveal more complex chronic
      health patterns masked by broader racial groupings.

PMID- 24920187
TI  - Changes in the distribution of multispecies pest assemblages affect levels of
      crop damage in warming tropical Andes.
AB  - Climate induced species range shifts might create novel interactions among
      species that may outweigh direct climatic effects. In an agricultural context,
      climate change might alter the intensity of competition or facilitation
      interactions among pests with, potentially, negative consequences on the levels
      of damage to crop. This could threaten the productivity of agricultural systems
      and have negative impacts on food security, but has yet been poorly considered in
      studies. In this contribution, we constructed and evaluated process-based species
      distribution models for three invasive potato pests in the Tropical Andean
      Region. These three species have been found to co-occur and interact within the
      same potato tuber, causing different levels of damage to crop. Our models allowed
      us to predict the current and future distribution of the species and therefore,
      to assess how damage to crop might change in the future due to novel
      interactions. In general, our study revealed the main challenges related to
      distribution modeling of invasive pests in highly heterogeneous regions. It
      yielded different results for the three species, both in terms of accuracy and
      distribution, with one species surviving best at lower altitudes and the other
      two performing better at higher altitudes. As to future distributions our results
      suggested that the three species will show different responses to climate change,
      with one of them expanding to higher altitudes, another contracting its range and
      the other shifting its distribution to higher altitudes. These changes will
      result in novel areas of co-occurrence and hence, interactions of the pests,
      which will cause different levels of damage to crop. Combining population
      dynamics and species distribution models that incorporate interspecific trade-off
      relationships in different environments revealed a powerful approach to provide
      predictions about the response of an assemblage of interacting species to future
      environmental changes and their impact on process rates. 

PMID- 24920188
TI  - Protocol for a systematic review and meta-analysis of cognitive-behavioural
      therapy for social anxiety disorder in psychosis.
AB  - BACKGROUND: Social anxiety is among the most prevalent and debilitating affective
      disturbances manifest in people with psychosis. It is usually accompanied by high
      levels of depression and leads to significant social disability, lower quality of
      life and poorer prognosis as it raises the possibility of an early relapse.
      Despite its elevated prevalence and severity in psychosis, social anxiety remains
      under-recognized and under-treated. Cognitive-behavioural therapy is recommended
      for the treatment of people with psychosis. However, its focus and evaluation has
      primarily revolved around the reduction of psychotic symptoms, and not for co
      morbid affective disturbances such as social anxiety. There is lack of evidence
      on the clinical effectiveness and cost-effectiveness of cognitive-behavioural
      interventions for the treatment of social anxiety disorder in psychosis.
      METHODS/DESIGN: Electronic databases will be systematically searched for
      randomised controlled trials and quasi-experimental studies investigating the
      effectiveness and cost-effectiveness of cognitive-behavioural interventions for
      the treatment of social anxiety disorder in people with psychosis. Grey
      literature will also be searched by screening trial registers. Only studies
      published in English will be included in the review. Date restrictions will not
      be applied. Eligible studies will have as the primary outcome social anxiety
      (continuous data) measured using any psychometrically validated scale both self
      reported and clinician administered. Secondary outcomes will include general
      anxiety symptoms, distress, depression, positive and negative symptoms of
      schizophrenia, and quality of life measured using any psychometrically validated
      scale, both self-reported and clinician administered, and the cost of cognitive
      behaviour therapy (CBT) intervention (with another treatment or treatment-as
      usual). CONCLUSIONS: This review will provide an evidence synthesis of the
      effectiveness and cost-effectiveness of cognitive-behavioural interventions for
      the treatment of social anxiety disorder in people with psychosis. The review
      will identify the specific intervention components associated with effectiveness
      which will facilitate the translation of the existing evidence to the development
      of new, targeted interventions optimising these components. In doing so, this
      review will provide recommendations for the treatment of social anxiety and
      associated distress in psychosis and will further inform the development of
      future interventions in this area. TRIAL REGISTRATION: PROSPERO registration
      numberCRD42014009052.

PMID- 24920186
TI  - Using zebrafish to study podocyte genesis during kidney development and
      regeneration.
AB  - During development, vertebrates form a progression of up to three different
      kidneys that are comprised of functional units termed nephrons. Nephron
      composition is highly conserved across species, and an increasing appreciation of
      the similarities between zebrafish and mammalian nephron cell types has
      positioned the zebrafish as a relevant genetic system for nephrogenesis studies.
      A key component of the nephron blood filter is a specialized epithelial cell
      known as the podocyte. Podocyte research is of the utmost importance as a vast
      majority of renal diseases initiate with the dysfunction or loss of podocytes,
      resulting in a condition known as proteinuria that causes nephron degeneration
      and eventually leads to kidney failure. Understanding how podocytes develop
      during organogenesis may elucidate new ways to promote nephron health by
      stimulating podocyte replacement in kidney disease patients. In this review, we
      discuss how the zebrafish model can be used to study kidney development, and how
      zebrafish research has provided new insights into podocyte lineage specification
      and differentiation. Further, we discuss the recent discovery of podocyte
      regeneration in adult zebrafish, and explore how continued basic research using
      zebrafish can provide important knowledge about podocyte genesis in embryonic and
      adult environments. genesis 52:771-792, 2014. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24920189
TI  - p38 Mitogen-activated protein kinase is required for electroacupuncture
      restoration of CD4+/CD8+ homeostasis and cytokine expression in a rodent model of
      surgical trauma.
AB  - Cumulative evidences addressed that electroacupuncture (EA) was favorably
      effective in the treatment of trauma stress-induced immunodeficiency and physical
      disorders. However, the salutary effects of EA under operation trauma conditions
      mediated via p38 MAPK remain unknown. Hence, our study aimed to further
      investigate the effects of EA on CD4(+)/CD8(+) homeostasis and cytokine
      expressions, and evaluate the p38 MAPK signaling regulatory mechanism of EA
      effects. 

PMID- 24920190
TI  - Effects of Phyllanthus sellowianus Mull Arg. extracts on the rheological
      properties of human erythrocytes.
AB  - Phyllanthus sellowianus extracts have been used in Argentina since colonial times
      in the treatment of diabetes. The in vitro biorheological and hemoagglutinant
      action of different extracts of P. sellowianus bark on human erythrocytes (RBC)
      were studied. RBCs were incubated in vitro with four aqueous extracts:
      Maceration; Controlled Digestion (PD); Decoction; and Infusion. Biorheological
      parameters (deformability, membrane surface viscosity, elastic modulus, and
      dynamic viscolelasticity) were determined with an Erythrodeformeter, and
      erythrocyte adhesion was characterized by image digital analysis.
      Immunohematological assays in RBC incubated with all the extracts showed large
      globular aggregates and agglutination in human ABO blood group system. Isolated
      cell coefficient showed the increase of cell adhesion. Aggregated shape
      parameters were significantly higher than normal and they changed with the
      concentration, particularly of PD extracts. Rheological results showed that the
      extract biorheological action varies with the temperature used in the extract
      preparations. The results obtained are useful to study the action mechanism of
      extracts from P. sellowianus bark in order to evaluate its use as therapeutic
      agent in diabetes. Immunohematological Tests using ABO system showed its
      agglutinant power, which is of special interest in Immunohematology to be used as
      hemoclassifier. 

PMID- 24920191
TI  - Effects of intracavitary administration of Endostar combined with cisplatin in
      malignant pleural effusion and ascites.
AB  - This study evaluated the efficacy and safety of intracavitary administration of
      recombinant human endostatin (Endostar) combined with cisplatin chemotherapy in
      treating malignant pleural effusion and ascites. Forty-five patients with
      malignant pleural effusion and ascites were divided into the EP group (n = 23),
      who received Endostar and cisplatin intracavitarily, and P group (n = 22), who
      were intracavitarily treated with cisplatin only. Pleural effusion and ascites
      were completely drained before treatments. The treatment was administered once a
      week; two treatments were considered as one course. The outcome quality of life
      as well as toxicity were evaluated. The objective overall response and disease
      control rates were, respectively, 78.3 % (18/23) and 87.0 % (20/23) in EP group.
      In contrast, these parameters were significantly (p < 0.05) lower in P groups:
      40.9 % (9/22) and 59.1 % (13/22), respectively. The improvement rate of Karnofsky
      Performance Status was 87.0 % (20/23) in EP group versus 59.1 % (13/22) in P
      group (p < 0.05). All patients tolerated the combined treatment well, and no
      severe adverse effects were observed. Intracavitary injection of Endostar
      combined with cisplatin is effective and safe to treat malignant pleural effusion
      and ascites.

PMID- 24920192
TI  - CD117: a novel ancillary marker for papillary thyroid carcinoma in fine-needle
      aspiration biopsies.
AB  - BACKGROUND: c-KIT/CD117 down-regulation has been described in papillary thyroid
      carcinoma (PTC). In this study, the authors investigated CD117 as an ancillary
      immunocytochemical test for PTC in fine-needle aspiration biopsy (FNAB). METHODS:
      The expression of CD117 was assessed in cytologic samples of histologically
      confirmed classic PTC (n = 35) and in a control group of benign thyroid nodules
      (BTNs) (n = 30) using immunocytochemistry. The corresponding PTCs and BTNs from
      surgical resection specimens also were evaluated immunohistochemically for CD117.
      The expression of CD117 was assessed semiquantitatively using a scoring system
      from 0 to 5 that combined the proportion and the intensity of staining. RESULTS:
      The difference in immunoreactivity for CD117 between PTC and BTNs was highly
      significant both in FNAB samples and in the corresponding histology samples (P <
      .0001). On cytology, most PTCs (74%; n = 26) lacked immunoreactivity for CD117,
      and 9 samples (26%) had faint reactivity in <2% of tumor cells (score, 0). In
      contrast, all BTNs (100%; n = 30) were positive for CD117, and at least 50% of
      the cells (score, 2-4) were positive in 79% (n = 24) of BTNs. Results with
      corresponding histology were similar to the cytology results; most PTCs (89%; n =
      31) lacked immunoreactivity for CD117, and 4 samples (11%) had faint reactivity
      in <2% of tumor cells. In contrast, all BTNs (n = 30) were variably positive for
      CD117 (score, 2-4). Normal follicular epithelium also was positive for CD117
      (score, 2-4). CONCLUSIONS: CD117 is expressed in both normal follicular
      epithelium and in BTNs. In contrast, expression of CD117 is absent or weak in
      PTC. These results suggest that CD117 may be useful as an ancillary marker for
      PTC.

PMID- 24920193
TI  - Characterization of the multigene family TaHKT 2;1 in bread wheat and the role of
      gene members in plant Na(+) and K(+) status.
AB  - BACKGROUND: A member of the TaHKT2;1 multigene family was previously identified
      as a Na(+) transporter with a possible role in root Na(+) uptake. In the present
      study, the existing full-length cDNA of this member was used as a basis to query
      the International Wheat Genome Survey Sequence to identify all members of the
      TaHKT2;1 family. Individual TaHKT2;1 genes were subsequently studied for gene and
      predicted protein structures, promoter variability, tissue expression and their
      role in Na(+) and K(+) status of wheat. RESULTS: Six TaHKT2;1 genes were
      characterized which included four functional genes (TaHKT2;1 7AL-1, TaHKT2;1 7BL
      1, TaHKT2;1 7BL-2 and TaHKT2;1 7DL-1) and two pseudogenes (TaHKT2;1 7AL-2 and
      TaHKT2;1 7AL-3), on chromosomes 7A, 7B and 7D of hexaploid wheat. Variability in
      protein domains for cation specificity and in cis-regulatory elements for salt
      response in gene promoters, were identified amongst the functional TaHKT2;1
      members. The functional genes were expressed under low and high NaCl conditions
      in roots and leaf sheaths, but were down regulated in leaf blades. Alternative
      splicing events were evident in TaHKT2;1 7AL-1. Aneuploid lines null for each
      functional gene were grown in high NaCl nutrient solution culture to identify
      potential role of each TaHKT2;1 member. Aneuploid lines null for TaHKT2;1 7AL-1,
      TaHKT2;1 7BL-1 and TaHKT2;1 7BL-2 showed no difference in Na(+) concentration
      between Chinese Spring except for higher Na(+) in sheaths. The same aneuploid
      lines had lower K(+) in roots, sheath and youngest fully expanded leaf but only
      under high (200 mM) NaCl in the external solution. There was no difference in
      Na(+) or K(+) concentration for any treatment between aneuploid line null for the
      TaHKT2;1 7DL-1 gene and Chinese Spring. CONCLUSIONS: TaHKT2;1 is a complex family
      consisting of pseudogenes and functional members. TaHKT2;1 genes do not have an
      apparent role in controlling root Na(+) uptake in bread wheat seedlings under
      experimental conditions in this study, contrary to existing hypotheses. However,
      TaHKT2;1 genes or, indeed other genes in the same chromosome region on 7AL, are
      candidates that may control Na(+) transport from root to sheath and regulate K(+)
      levels in different plant tissues.

PMID- 24920194
TI  - Network vs. pairwise meta-analyses: a case study of the impact of an evidence
      synthesis paradigm on value of information outcomes.
AB  - OBJECTIVE: To evaluate the impact of using two evidence-synthesis paradigms,
      pairwise meta-analysis (PMA) vs. network meta-analysis (NMA), on the expected
      value of information (EVI) outcomes, using pharmacotherapy of chronic obstructive
      pulmonary disease as a case study. METHODS: Bayesian random-effects PMAs were
      performed for each pharmacotherapy vs. placebo, and a Bayesian random-effects NMA
      was performed combining both placebo-controlled and head-to-head trials. Both
      provided comparative rate ratio (RR) estimates between each pharmacotherapy vs.
      placebo. A Markov model was developed to project costs and quality-adjusted life
      years of five commonly used treatments for chronic obsructive pulmonary disorder.
      RRs for the treatment effect compared with placebo derived using PMA and NMA were
      used alongside values from the literature to populate the model. In addition to
      standard cost-effectiveness outputs, we calculated and compared the expected
      value of perfect information (EVPI) and the expected value of partial perfect
      information (EVPPI) for treatment effects, for comparisons that included all or a
      subset of treatments. RESULTS: The network of evidence included five different
      treatments, compared in 19 randomized controlled trials (RCTs), which in total
      included 28,172 individuals. The cost-effectiveness outcomes were similar between
      the two evidence-synthesis paradigms. The individual EVPI for all treatments was
      Can$1,262 for PMA-based analyses and Can$572 for NMA-based analyses. For all
      comparisons involving two, three, or four treatments, the comparison with the
      highest EVPI was different between the two methods. Similarly, the choice of PMA
      or NMA had resulted in substantially different EVPPI rankings. CONCLUSION: Our
      case study shows that the choice of PMA or NMA can have significant effects on
      the EVI results. Under comparable conditions, the incorporation of more evidence
      in the NMA most likely increases the precision of estimates and therefore is
      likely to result in lower EVI outcomes. As our study demonstrates, the difference
      in EVI outcomes can be substantial, potentially affecting the decision to conduct
      research and the design of future research.

PMID- 24920195
TI  - Cost-utility analysis of chemotherapy regimens in elderly patients with stage III
      colon cancer.
AB  - BACKGROUND: Chemotherapy prolongs survival for stage III colon cancer patients
      but community-level evidence on the effectiveness and cost effectiveness of
      treatment for elderly patients is limited. Comparisons were between patients
      receiving no chemotherapy, 5-fluorouracil (5-FU), and FOLFOX (5-FU +
      oxaliplatin). METHODS: A retrospective cohort study was conducted using the
      Surveillance Epidemiology, and End Results (SEER)-Medicare linked database.
      Patients (>=65 years) with American Joint Committee on Cancer stage III colon
      cancer at diagnosis in 2004-2009 were identified. The 3-way propensity score
      matched sample included 3,534 patients. Effectiveness was measured in life-years
      and quality-adjusted life-years (QALYs). Medicare costs (2010 US dollars) were
      estimated from diagnosis until death or end of study. RESULTS: FOLFOX patients
      experienced 6.06 median life-years and 4.73 QALYs. Patients on 5-FU had 5.75
      median life-years and 4.50 median QALYs, compared to 3.42 and 2.51, respectively,
      for the no chemotherapy patients. Average total healthcare costs ranged from
      US$85,422 for no chemotherapy to US$168,628 for FOLFOX. Incremental cost
      effectiveness ratios (ICER) for 5-FU versus no chemotherapy were US$17,131 per
      life-year gained and US$20,058 per QALY gained. ICERs for FOLFOX versus 5-FU were
      US$139,646 per life-year gained and US$188,218 per QALY gained. Results appear to
      be sensitive to age, suggesting that FOLFOX performs better for patients 65-69
      and 80+ years old while 5-FU appears most effective and cost effective for the
      age groups 70-74 and 75-79 years. CONCLUSION: FOLFOX appears more effective and
      cost effective than other strategies for colon cancer treatment of older
      patients. Results were sensitive to age, with ICERs exhibiting a U-shaped
      pattern.

PMID- 24920196
TI  - Reconceptualising the external validity of discrete choice experiments.
AB  - External validity is a crucial but under-researched topic when considering using
      discrete choice experiment (DCE) results to inform decision making in clinical,
      commercial or policy contexts. We present the theory and tests traditionally used
      to explore external validity that focus on a comparison of final outcomes and
      review how this traditional definition has been empirically tested in health
      economics and other sectors (such as transport, environment and marketing) in
      which DCE methods are applied. While an important component, we argue that the
      investigation of external validity should be much broader than a comparison of
      final outcomes. In doing so, we introduce a new and more comprehensive
      conceptualisation of external validity, closely linked to process validity, that
      moves us from the simple characterisation of a model as being or not being
      externally valid on the basis of predictive performance, to the concept that
      external validity should be an objective pursued from the initial
      conceptualisation and design of any DCE. We discuss how such a broader definition
      of external validity can be fruitfully used and suggest innovative ways in which
      it can be explored in practice. 

PMID- 24920197
TI  - Ex-PRESS outcomes using mitomycin-C, Ologen alone, Ologen with 5-fluorouracil.
AB  - To compare the complication rate and effectiveness of mitomycin C (MMC), Ologen
      alone, and Ologen with 5-fluorouracil (5-FU) as adjunctives with Ex-PRESS mini
      shunt for medically uncontrolled glaucoma. Retrospective comparative study of 59
      Ex-PRESS mini shunt trabeculectomy operations coupled with Ologen implantation
      alone, transient MMC application or Ologen implantation with 5-FU as adjunctive
      treatment. Eight eyes (7 patients) received Ologen alone, 37 eyes (34 patients)
      received MMC, and 14 eyes (14 patients) received Ologen with 5-FU as adjunctive
      therapy. Baseline characteristics, adjunctive used during operation, along with
      outcomes including intraocular pressure (IOP), number of anti-hypertensive drops,
      visual acuity, and complications were documented and compared. The primary
      outcome was IOP at 12 months. Variables were compared with r * c Fisher tests.
      The Ologen only group had a significantly higher IOP at 12 months (20.5 +/- 10.23
      mmHg) compared with Ologen combined with 5-FU (12.2 +/- 1.47 mmHg) or MMC (13.8
      +/- 4.37 mmHg) (p = 0.015, linear mixed model). The Ologen only cohort also had a
      higher re-operation rate (p = 0.01, Fisher's Exact Test) and higher rate of bleb
      leak (p = 0.02, Fisher's Exact Test). Visual acuity was similar among all three
      groups. 5-FU with Ologen is as effective as MMC in maintaining IOP following Ex
      PRESS shunt surgery at 1 year. However, Ologen alone may not be as effective as
      the other two adjunctive agents.

PMID- 24920198
TI  - The double-hit effect of childhood maltreatment on drug relapse.

PMID- 24920199
TI  - A fine balance.

PMID- 24920200
TI  - Psychological management of wound pruritus.
AB  - OBJECTIVE: To explore the psychological treatment options for pruritus in
      patients with wounds. METHOD: This study employed a narrative design with a
      search being completed using the databases Academic Search Complete, Google
      Scholar, PsycInfo, PsycARTICLES, Medline and CINAHL Plus. All articles between
      1980-2013 that included the following search terms: [pruritus OR itch OR itching]
      AND [management OR psychological interventions OR treatment] AND [wounds OR burns
      OR wounds burns] were included in the review. RESULTS: A number of psychological
      treatments options emerged from the literature search that were suggested to be
      effective for treating itching. These included methods such as habit reversal,
      suggestions, relaxation, massage and itch-coping programmes. Each of these
      methods showed potential for improving the patient experience by reducing
      itching, although the research evidence is currently somewhat limited.
      CONCLUSION: Although itching is a common symptom in wounds, the use of
      psychological treatments for this may be rather limited. The treatments discussed
      show promise and their use should be a welcome addition to the healthcare
      professional's armoury for working with people with wounds. DECLARATION OF
      INTEREST: There were no external sources of funding for this study. The authors
      have no conflicts of interest to declare.

PMID- 24920201
TI  - Practical limitations of two devices used for the measurement of sub-bandage
      pressure: implications for clinical practice.
AB  - OBJECTIVE: This study was undertaken to examine the accuracy of two hand-held
      devices commonly used to measure the pressures produced by extensible bandages.
      METHOD: The performance of the pneumatic sensors of two devices, the Kikuhime and
      Picopress instruments was first examined in air in a compression chamber, then
      subsequently beneath multiple layers of bandages applied to standard cylinders
      with predetermined levels of tension. RESULTS: In the compression chamber, both
      instruments provided readings that were typically within 1 mmHg of the reference
      value, but on curved formers in free air or beneath bandages the accuracy of both
      sensors was greatly reduced, influenced both by the curvature of the cylinders
      and the volume of air contained in the sensor capsule. The Picopress instrument
      recorded pressures up to 70% higher than predicted, particularly on the smaller
      cylinders and at the lower end of the pressure range (circa 20mmHg). At 40mmHg
      measured pressure were around 40% higher than predicted values in some instances.
      The accuracy of the Kikuhime was greatly influenced by the calibration technique
      but percentage deviations as high as 150% were recorded in some tests.
      CONCLUSION: Pneumatic pressure sensors used to record the pressures developed
      beneath compression bandages are much less accurate than is commonly believed.
      Calibration studies using air chambers or water tanks have no relevance to the
      normal clinical use of these devices. These limitations should be considered by
      clinicians when making judgments about the performance of other medical devices
      such as bandages or stockings. They also call into question the validity of many
      published studies which rely upon such measurements. DECLARATION OF INTEREST:
      This project was generously supported by 3M Healthcare who provided a small
      research grant to assist with the costs associated with the construction of the
      test equipment.

PMID- 24920202
TI  - Wound infections and healing: are they contributing factors for carcinogenesis?
AB  - The link between inflammation and tumourisation has long been considered as a key
      event in clinical cancer development. Inflammation and inflammatory diseases can
      be caused by many factors including infectious agents, altered genetics and
      various degrees of injuries from simple cuts to traumatic wounds, such as those
      suffered in battlefield. Improved management of all wound types is critical in
      protecting affected individuals against the development of tumourisation cues,
      which may potentially lead to cancer development. There have been numerous
      studies on the mechanism of inflammation-induced tumourisation. Thus, in this
      mini review, we summarised evidence demonstrating the potential link between
      infectious agents and their moonlight proteins, wounding, trauma, overactive
      repair mechanisms, and carcinogenesis. 

PMID- 24920203
TI  - Diabetic bullae: a case series and a new model of surgical management.
AB  - Bullosis diabeticorum is considered a rare skin manifestation of diabetes
      mellitus. Tense blisters appear rapidly, mostly on the feet, the cause of which
      is unclear, with multiple pathophysiologies hypothesised. This is a retrospective
      review of 4 diabetic patients who presented over six months with diabetic bullae;
      the condition may therefore not be as rare as commonly believed. All the patients
      had early surgical debridement followed by topical negative pressure wound
      dressings. A multidisciplinary team that included vascular surgeons,
      diabetologists, diabetic foot care team, wound care team, physiotherapists and
      occupational therapists managed the patients and none of them required
      amputations. We propose an alternative way of managing these patients with early
      surgical debridement followed by topical negative pressure wound dressing. 

PMID- 24920204
TI  - Quality of life and self-esteem in patients with paraplegia and pressure ulcers:
      a controlled cross-sectional study.
AB  - OBJECTIVE: To evaluate health-related quality of life (HRQoL) and self-esteem in
      patients with traumatic spinal cord injury (SCI) and pressure ulcers. METHOD:
      This study was a controlled cross-sectional study. HRQoL was assessed using the
      generic Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
      questionnaire and the Rosenberg Self-Esteem/UNIFESP-EPM Scale. A total of 120
      patients with traumatic SCI were included in the sample, of which 60 had pressure
      ulcers and were assigned to the study group, and 60 had no pressure ulcers and
      were assigned to the control group. Statistical analysis was performed using the
      chi-square test, Fisher's exact test, and Student's t-test. RESULTS: Of the 60
      patients in the study group, 83.3% were men and the mean age was 38.17 years (SD
      = 9.08 years). When compared with controls, patients in the study group reported
      significantly lower scores (worse health status) on all SF-36 subscales (p less
      than or equal to 0.0013) except for general health (p=0.109). The RSE/UNIFESP-EMP
      scale total score indicated that patients with pressure ulcers had significantly
      lower self-esteem than controls (p<0.001). CONCLUSION: Pressure ulcers had an
      adverse impact on the HRQoL and self-esteem of patients with SCI. DECLARATION OF
      INTEREST: There were no external sources of funding for this study. The authors
      have no conflicts of interest to declare.

PMID- 24920205
TI  - The use of Surgihoney to prevent or eradicate bacterial colonisation in dressing
      oncology long vascular lines.
AB  - OBJECTIVE: A pilot evaluation was performed to assess the effects of Surgihoney,
      an engineered honey with highly active antimicrobial activity, on bacterial
      colonisation in long lines in oncology patients. METHOD: This prospective service
      evaluation was conducted at Hampshire Hospitals NHS Foundation Trust (HHFT) in
      England, UK, between 2012 and 2013. The study population consisted of oncology
      patients with central intravenous lines who were receiving outpatient
      chemotherapy. All patients were offered line dressing with or without Surgihoney,
      applied to the line exit site. RESULTS: The primary outcome measure of the study
      was the presence or absence of bacterial colonisation of the line site. There
      were 30 patients in each arm - with or without Surgihoney. In the Surgihoney arm,
      2 patients with existing line site colonisation were cleared of bacterial
      colonisation and none acquired colonisation during the study period. In the non
      treatment arm, 6 patients were colonised at the line site prior to screening or
      during the evaluation. Bacterial colonisation was maintained throughout the
      period. CONCLUSION: Surgihoney is an effective antimicrobial line-site dressing,
      significantly reducing line site colonisation and eradicating existing
      colonisation. It was well tolerated by the patients. DECLARATION OF INTEREST:
      Surgihoney supplies were donated by Healing Honey International (HHI) who also
      provided some funding to Hampshire Hospitals Foundation Trust for microbiological
      investigation. MD and JC have provided clinical advice in an advisory capacity to
      HHI.

PMID- 24920206
TI  - Acetyltransferase SAS2 and sirtuin SIR2, respectively, control flocculation and
      biofilm formation in wine yeast.
AB  - Cell-to-cell and cell-to-environment interactions of microorganisms are of
      substantial relevance for their biotechnological use. In the yeast Saccharomyces
      cerevisiae, flocculation can be an advantage to clarify final liquid products
      after fermentation, and biofilm formation may be relevant for the encapsulation
      of strains of interest. The adhesion properties of wine yeast strains can be
      modified by the genetic manipulation of transcriptional regulatory proteins, such
      as histone deacetylases, and acetylases. Sirtuin SIR2 is essential for the
      formation of mat structures, a kind of biofilm that requires the expression of
      cell-wall protein FLO11 as its deletion reduces FLO11 expression, and adhesion of
      cells to themselves and to agar in a commercial wine strain. Deletion of
      acetyltransferase GCN5 leads to a similar phenotype. A naturally flocculant wine
      yeast strain called P2 was characterized. Its flocculation happens only during
      grape juice fermentation and is due to the presence of a highly transcribed
      version of flocculin FLO5, linked to the presence of a delta sequence in the
      promoter. Deletion of acetyltransferase SAS2 enhances this phenotype and maltose
      fermentation even more. Therefore, the manipulation of acetylation/deacetylation
      machinery members is a valid way to alter the interaction of industrial yeast to
      their environment. 

PMID- 24920207
TI  - An automated causality assessment algorithm to detect drug-induced liver injury
      in electronic medical record data.
AB  - PURPOSE: The aim of this study was to develop an automated causality assessment
      algorithm to identify drug-induced liver injury. METHODS: The Roussel Uclaf
      Causality Assessment Method (RUCAM) is an algorithm for determining the causal
      association between a drug and liver injury. In collaboration with hepatology
      experts, definitions were developed for the RUCAM criteria to operationalize an
      electronic RUCAM (eRUCAM). The eRUCAM was tested in a population of patients
      taking 14 drugs with a characteristic phenotype for liver injury. Quality
      assurance for programming specifications involved comparisons between scores
      generated by the eRUCAM, for probable and highly probable cases, and expert
      manual RUCAM (n = 20). Concordance between eRUCAM and manual RUCAM subscores and
      total score was tested using the Wilcoxon signed rank test. RESULTS: Causality
      scores were the same for 6 of 20 patients (30%) by manual and eRUCAM algorithms.
      Analysis of subscores revealed >=80% concordance between manual and eRUCAM for
      five of the seven criteria. In general, the total scores tended to be higher for
      the eRUCAM compared with the manual RUCAM. Programming issues were identified for
      criterion 5 'non-drug causes of liver injury' where significant differences
      existed between manual and eRUCAM scoring (p = 0.001). For criterion 5, identical
      scores occurred in 9 of 20 patients (45%), and manual review identified
      additional codes, timing criteria, and laboratory results for improving
      subsequent eRUCAM revisions. CONCLUSION: The eRUCAM had generally good
      concordance with manual RUCAM scoring. These preliminary findings suggest that
      the eRUCAM algorithm is feasible and could have application in clinical practice
      and drug safety surveillance.

PMID- 24920208
TI  - Using a non-invasive technique in nutrition: synchrotron radiation infrared
      microspectroscopy spectroscopic characterization of oil seeds treated with
      different processing conditions on molecular spectral factors influencing
      nutrient delivery.
AB  - Non-invasive techniques are a key to study nutrition and structure interaction.
      Fourier transform infrared microspectroscopy coupled with a synchrotron radiation
      source (SR-IMS) is a rapid, non-invasive, and non-destructive bioanalytical
      technique. To understand internal structure changes in relation to nutrient
      availability in oil seed processing is vital to find optimal processing
      conditions. The objective of this study was to use a synchrotron-based
      bioanalytical technique SR-IMS as a non-invasive and non-destructive tool to
      study the effects of heat-processing methods and oil seed canola type on modeled
      protein structure based on spectral data within intact tissue that were randomly
      selected and quantify the relationship between the modeled protein structure and
      protein nutrient supply to ruminants. The results showed that the moisture heat
      related processing significantly changed (p<0.05) modeled protein structures
      compared to the raw canola (control) and those processing by dry heating. The
      moisture heating increased (p<0.05) spectral intensities of amide I, amide II,
      alpha-helices, and beta-sheets but decreased (p<0.05) the ratio of modeled alpha
      helices to beta-sheet spectral intensity. There was no difference (p>0.05) in the
      protein spectral profile between the raw and dry-heated canola tissue and between
      yellow- and brown-type canola tissue. The results indicated that different heat
      processing methods have different impacts on the protein inherent structure. The
      protein intrinsic structure in canola seed tissue was more sensitive and more
      response to the moisture heating in comparison to the dry heating. These changes
      are expected to be related to the nutritive value. However, the current study is
      based on limited samples, and more large-scale studies are needed to confirm our
      findings.

PMID- 24920209
TI  - Effectiveness of bacteriophages in the sputum of cystic fibrosis patients.
AB  - Bacteriophages have been shown to be effective for treating acute infections of
      the respiratory tract caused by antibiotic-resistant bacteria in animal models,
      but no evidence has yet been presented of their activity against pathogens in
      complex biological samples from chronically infected patients. We assessed the
      efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa
      following its addition to 58 sputum samples from cystic fibrosis (CF) patients
      collected at three different hospitals. Ten samples that did not contain P.
      aeruginosa were not analysed further. In the remaining 48 samples, the addition
      of bacteriophages led to a significant decrease in the levels of P. aeruginosa
      strains, as shown by comparison with controls, taking two variables (time and
      bacteriophages) into account (p = 0.024). In 45.8% of these samples, this
      decrease was accompanied by an increase in the number of bacteriophages. We also
      tested each of the ten bacteriophages individually against 20 colonies from each
      of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of
      the samples. An analysis of the clinical data revealed no correlation between
      patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment,
      FEV1 (forced expiratory volume in the first second) and the efficacy of
      bacteriophages. The demonstration that bacteriophages infect their bacterial
      hosts in the sputum environment, regardless of the clinical characteristics of
      the patients, represents a major step towards the development of bacteriophage
      therapy to treat chronic lung infections. 

PMID- 24920210
TI  - Frequent and prolonged nocturnal occupation of port areas by Yangtze finless
      porpoises (Neophocaena asiaeorientalis): forced choice for feeding?
AB  - During the Yangtze Freshwater Dolphin Expedition 2012, Yangtze finless porpoises
      (Neophocaena asiaeorientalis) were acoustically monitored in 9 port areas at
      night. During 6566 min of nocturnal monitoring, porpoise sonar was detected for
      488 min (7.43% of the total time). Of all 81 encounters, the longest echolocation
      span obtained was 102.9 min, suggesting frequent and prolonged porpoise
      occupation of the port areas. A combined total of 2091 click trains were
      recorded, with 129 (6.2%) containing minimum inter-click intervals (ICIs) below
      10 ms (termed a buzz). Buzzes with a decrease in ICIs and search and approach
      phases that resembled feeding echolocation signals accounted for 44.2% (N=52) of
      all buzzes. Buzzes with an increase in ICIs, suggesting a mirrored prey capture
      phase, accounted for 20.2% (N=26) and could reflect attempts to locate escaped
      prey because they were followed by approach-phase feeding buzzes. Anecdotal
      evidence of porpoises fleeing the proximity of vessels was observed. The
      recordings indicating clusters of porpoises feeding near the port areas suggest a
      forced choice for feeding due to the relatively higher prey availability in the
      port areas compared to other areas in the Yangtze River that are probably
      overfished.

PMID- 24920211
TI  - Anxiolytic and antidepressant like effects of natural food flavour (E)-methyl
      isoeugenol.
AB  - (E)-methyl isoeugenol (MIE) is a natural food flavour that constitutes 93.7% of
      an essential oil from Pimenta pseudocaryophyllus leaf. The leaf extracts of this
      species are used as a calming agent. As a ubiquitous food additive, the
      application of MIE for treating mood disorders appears to be globally attractive.
      Hence, we sought to evaluate general pharmacological activities, anticonvulsant,
      anxiolytic and antidepressant effects and the possible mechanisms of MIE actions.
      Administration of MIE was carried out prior to the exposure of a male Swiss mice
      to general behavioural tests, barbiturate sleep, PTZ-induced convulsion, light
      dark box (LDB), elevated plus maze (EPM), wire hanging, open field (OF) and
      forced swimming test (FST). The involvement of monoamine system was studied by
      mice pretreatment with WAY100635 (antagonist of 5-HT1A), alpha-methyl-p-tyrosine
      (AMPT; depletor of catecholamine) or p-chlorophenylalanine (PCPA; depletor of
      serotonin storage). There was no record of neurotoxic effect or animal's death
      during the course of general pharmacological tests. MIE at 250 and 500 mg kg(-1)
      potentiated the hypnotic effect of sodium pentobarbital. However, MIE did not
      protect against PTZ-induced convulsion. Except for MIE at 500 mg kg(-1),
      parameters evaluated in the LDB, EPM and OF demonstrated an anxiolytic like
      property of MIE. This effect was blocked by WAY100635 pretreatment. MIE at 500 mg
      kg(-1) elicited a reduction in locomotor activity of the mice in the OF. Anti
      immobility effect of MIE 250 mg kg(-1) in the FST suggested an antidepressive
      like property. Unlike AMPT, pretreatment with PCPA reversed the antidepressant
      like effect of MIE. Our findings demonstrated anxiolytic and antidepressant like
      properties of (E)-methyl isoeugenol and suggested the participation of
      serotonergic pathways. 

PMID- 24920212
TI  - Incorporation and redistribution of impurities into silicon nanowires during
      metal-particle-assisted growth.
AB  - The incorporation of metal atoms into silicon nanowires during metal-particle
      assisted growth is a critical issue for various nanowire-based applications. Here
      we have been able to access directly the incorporation and redistribution of
      metal atoms into silicon nanowires produced by two different processes at growth
      rates ranging from 3 to 40 nm s(-1), by using laser-assisted atom probe
      tomography and scanning transmission electron microscopy. We find that the
      concentration of metal impurities in crystalline silicon nanowires increases with
      the growth rate and can reach a level of two orders of magnitude higher than that
      in their equilibrium solubility. Moreover, we demonstrate that the impurities are
      first incorporated into nanowire volume and then segregate at defects such as the
      twin planes. A dimer-atom-insertion kinetic model is proposed to account for the
      impurity incorporation into nanowires.

PMID- 24920213
TI  - Novel N-terminal truncating CLCN1 mutation in severe Becker disease.

PMID- 24920214
TI  - Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF
      7 cells.
AB  - Compelling evidence demonstrated that melatonin increases p53 activity in cancer
      cells. p53 undergoes acetylation to be stabilized and activated for driving cells
      destined for apoptosis/growth inhibition. Over-expression of p300 induces p53
      acetylation, leading to cell growth arrest by increasing p21 expression. In turn,
      p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3
      ubiquitin ligase, promoting the proteasome-dependent p53 degradation. MDM2 entry
      into the nucleus is finely tuned by two different modulations: the ribosomal
      protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K-AkT
      dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the
      nuclear membrane. In addition, MDM2-dependent targeting of p53 is regulated in a
      nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth
      inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that
      this effect is associated with reduced MDM2 levels and increased p53 activity.
      Herein, we demonstrated that melatonin drastically down-regulates MDM2 gene
      expression and inhibits MDM2 shuttling into the nucleus, given that melatonin
      increases L11 and inhibits Akt-PI3K-dependent MDM2 phosphorylation. Melatonin
      induces a 3-fold increase in both MDMX and p300 levels, decreasing simultaneously
      Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin-treated
      cells display significantly higher values of both p53 and acetylated p53. Thus, a
      15-fold increase in p21 levels was observed in melatonin-treated cancer cells.
      Our results provide evidence that melatonin enhances p53 acetylation by
      modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding
      its anticancer effect. 

PMID- 24920215
TI  - Deficits in attention, motor control, and perception and increased risk of injury
      in children.

PMID- 24920216
TI  - Second Global Symposium on Health Systems Research: a conference impact
      evaluation.
AB  - Evaluation researchers have confirmed the importance of conference evaluation,
      but there remains little research on the topic, perhaps in part because
      evaluation methodology related to conference impact is underdeveloped. We
      conducted a study evaluating a 4-day long health conference, the Second Global
      Symposium on Health Systems Research (HSR), which took place in Beijing in
      November 2012. Using a conference evaluation framework and a mixed-methods
      approach that involved in-conference surveys, in-conference interviews and 7
      month post-conference interviews, we evaluated the impact of the Symposium on
      attendees' work and the field of health systems research. The three major impacts
      on participants' work were new knowledge, new skills and new networks, and many
      participants were able to provide examples of how obtaining new knowledge, skills
      or collaborations had changed the way they conduct their work. Participants noted
      that the Symposium influenced the field of HSR only in so far as it influenced
      the capacity of stakeholders, but did not lead to any high level agenda or policy
      changes, perhaps due to the insufficient length of time (7 months) between the
      Symposium and post-conference follow-up. This study provides an illustration of a
      framework useful for conference organizers in the evaluation of future
      conferences, and of a unique methodology for evaluation researchers. 

PMID- 24920217
TI  - Determinants of life expectancy in the Eastern Mediterranean Region.
AB  - BACKGROUND: Although the Eastern Mediterranean Region (EMR) healthcare sector has
      been expanding rapidly, many differences exist across socioeconomic status,
      clinical practice standards and healthcare systems. OBJECTIVE: Predict production
      functions of health by measuring socioeconomic and expenditure factors that
      impact life expectancy in the EMR. METHODS: Data from the World Health
      Organization (WHO) Global Health Observatory and the World Bank were used for
      this cross-sectional, time-series study spanning 21 nations in the EMR from 1995
      to 2010. The primary outcome was life expectancy at birth. Covariates of interest
      included sociodemographic and health indicators. To both establish and validate
      appropriate categorization of countries, a cluster analysis was undertaken to
      group cases by taking selected characteristics into account. A variance
      component, multilevel mixed-effects linear model was employed that incorporated a
      finite, Almon, distributed lag of 5 years and bootstrapping with 5000 simulations
      to model the production function of life expectancy. RESULTS: Results of the
      cluster analysis found four groupings. Clusters 1 and 2, composed of six total
      countries, generally represented non-industrialized/least developed countries.
      Clusters 3 and 4, totalling 15 nations, captured more industrialized nations.
      Overall, gross domestic product (GDP) (P = 0.011), vaccination averages (P =
      0.026) and urbanization (P = 0.026), were significant positive predictors of life
      expectancy. No significant predictors existed for Cluster 1 countries. Among
      Cluster 2 nations, physician density (P = 0.014) and vaccination averages (P =
      0.044) were significant positive predictors. GDP (P = 0.037) and literacy (P =
      0.014) were positive significant predictors among Cluster 3 nations. GDP (P =
      0.002), health expenditures (P = 0.002) and vaccination averages (P = 0.014) were
      positive significant predictors in Cluster 4 countries. CONCLUSION: Predictors of
      life expectancy differed between non-industrialized and industrialized nations,
      with the exception of vaccination averages. Non-industrialized/least developed
      nations were associated with adjusted life expectancies of >14% lower than their
      industrialized peers. Continued work to address differences in the quality of and
      access to care in the EMR is required.

PMID- 24920218
TI  - Innovations in communication technologies for measles supplemental immunization
      activities: lessons from Kenya measles vaccination campaign, November 2012.
AB  - BACKGROUND: To achieve a measles free world, effective communication must be part
      of all elimination plans. The choice of communication approaches must be evidence
      based, locally appropriate, interactive and community owned. In this article, we
      document the innovative approach of using house visits supported by a web-enabled
      mobile phone application to create a real-time platform for adaptive management
      of supplemental measles immunization days in Kenya. METHODS: One thousand nine
      hundred and fifty-two Red Cross volunteers were recruited, trained and deployed
      to conduct house-to-house canvassing in 11 urban districts of Kenya. Three days
      before the campaigns, volunteers conducted house visits with a uniform approach
      and package of messages. All house visits were documented using a web-enabled
      mobile phone application (episurveyor(r)) that in real-time relayed information
      collected to all campaign management levels. During the campaigns, volunteers
      reported daily immunizations to their co-ordinators. Post-campaign house visits
      were also conducted within 4 days, to verify immunization of eligible children,
      assess information sources and detect adverse events following immunization.
      RESULTS: Fifty-six per cent of the 164 643 households visited said that they had
      heard about the planned 2012 measles vaccination campaign 1-3 days before start
      dates. Twenty-five per cent of households were likely to miss the measles
      supplemental dose if they had not been reassured by the house visit. Pre- and
      post-campaign reasons for refusal showed that targeted communication reduced
      misconceptions, fear of injections and trust in herbal remedies. Daily reporting
      of immunizations using mobile phones informed changes in service delivery plans
      for better immunization coverage. House visits were more remembered (70%) as
      sources of information compared with traditional mass awareness channels like
      megaphones (41%) and radio (37%). CONCLUSIONS: In high-density settlements, house
      to-house visits are easy and more penetrative compared with traditional media
      approaches. Using mobile phones to document campaign processes and outputs
      provides real time evidence for service delivery planning to improve immunization
      coverage.

PMID- 24920219
TI  - CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme
      neuroborreliosis and other diseases that cause neuroinflammation.
AB  - BACKGROUND: Laboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based
      on the detection of intrathecal Borrelia burgdorferi-specific antibody production
      (increased antibody index (AI)). However, AI can be negative in patients with
      early LNB and, conversely, can remain elevated for months after antibiotic
      treatment. Recent studies suggested that the chemokine CXCL13 in the
      cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin
      level determination has been used to assess the degree of neuroinflammation in a
      wide variety of diseases. METHODS: CXCL13 concentrations were analyzed in CSF
      samples of 366 retrospectively identified individuals. The samples represented
      pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne
      encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS
      herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection,
      and untreated neurosyphilis. The panel included also samples from patients with
      multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients,
      24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin
      concentrations were determined in a subset of these samples. RESULTS: The CXCL13
      concentrations in CSF samples of untreated LNB patients were significantly higher
      (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8
      pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from
      patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml).
      The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of
      99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations
      declined significantly from 16,770 pg/ml before to 109 pg/ml after the
      treatment.CSF neopterin concentration was significantly higher among the
      untreated LNB patients than in the non-LNB group. The use of neopterin
      concentration 10.6 nM as the cut-off led to a sensitivity of 88.6% and a
      specificity of 65.0% for the diagnosis of LNB. The CSF neopterin concentrations
      decreased statistically significantly with the treatment. CONCLUSIONS: These
      results clearly indicate that highly elevated CSF CXCL13 levels are strongly
      associated with untreated LNB. CXCL13 outperformed neopterin and appears to be an
      excellent biomarker in differentiating LNB from viral CNS infections and from
      other neuroinflammatory conditions.

PMID- 24920220
TI  - In vivo role of checkpoint kinase 2 in signaling telomere dysfunction.
AB  - Checkpoint kinase 2 (CHK2) is a downstream effector of the DNA damage response
      (DDR). Dysfunctional telomeres, either owing to critical shortening or disruption
      of the shelterin complex, activate a DDR, which eventually results in cell cycle
      arrest, senescence and/or apoptosis. Successive generations of telomerase
      deficient (Terc) mice show accelerated aging and shorter lifespan due to tissue
      atrophy and impaired organ regeneration associated to progressive telomere
      shortening. In contrast, mice deficient for the shelterin component TRF1 in
      stratified epithelia show a rapid and massive induction of DDR, leading to
      perinatal lethality and severe skin defects. In both mouse models, p53 deficiency
      can rescue survival. Here, we set to address the role of CHK2 in signaling
      telomere dysfunction in both mouse models. To this end, we generated mice doubly
      deficient for Chk2 and either Terc (Chk2(-/-) Terc(-/-) ) or Trf1
      (Trf1(Delta/Delta) K5Cre Chk2(-/-) ). We show that Chk2 deletion improves Terc
      associated phenotypes, including lifespan and age-associated pathologies.
      Similarly, Chk2 deficiency partially rescues perinatal mortality and attenuates
      degenerative pathologies of Trf1(Delta/Delta) K5Cre mice. In both cases, we show
      that the effects are mediated by a significant attenuation of p53/p21 signaling
      pathway. Our results represent the first demonstration of a role for CHK2 in the
      in vivo signaling of dysfunctional telomeres. 

PMID- 24920221
TI  - Clinical analysis of Kasabach-Merritt syndrome in 17 neonates.
AB  - BACKGROUND: Kasabach-Merritt syndrome (KMS) is characterized by giant hemangiomas
      and severe thrombocytopenia, which may result in life-threatening multi-organ
      hemorrhage. This study evaluated the clinical characteristics, treatments, and
      outcomes in neonates with KMS, in order to find out the optimal therapy. METHODS:
      The clinical data of 17 patients treated for KMS in the Department of Neonates,
      Guangzhou Women and Children's Medical Center, Guangzhou Medical University,
      China from January 2007 to January 2012 were retrospectively analyzed. RESULTS:
      The patients were 13 males and 4 females, aged 17 hours to 28 days at admission.
      Four patients had visceral hemangiomas and 13 had cutaneous hemangiomas. All had
      thrombocytopenia and coagulation disorders. Intravenous steroid therapy was
      initially effective in 6 patients (of which 3 relapsed) and ineffective in 11.
      The 11 patients with a poor response to steroids and the 3 who relapsed underwent
      arterial embolization therapy, which was effective in 9 patients (of which 1
      relapsed), ineffective in 4, and discontinued before completion in 1.
      Subsequently, four patients in whom arterial embolization therapy was ineffective
      and one with relapse were treated with vincristine. This was effective in four
      patients, and the other died of disseminated intravascular coagulation. Steroid
      therapy was effective in 35.3% of patients, but the relapse rate was 50%.
      Arterial embolization was effective in 64.3% of patients and vincristine was
      effective in 80%. CONCLUSIONS: In patients with neonatal KMS, steroid therapy has
      a low rate of effectiveness and high rate of relapse. Arterial embolization has a
      good rate of effectiveness. Combined steroid and embolization therapy should be
      considered for first-line treatment of neonatal KMS. If this approach is
      ineffective, vincristine may be useful.

PMID- 24920222
TI  - Wrong-side thoracentesis: lessons learned from root cause analysis.
AB  - IMPORTANCE: Despite the recognized value of the Joint Commission's Universal
      Protocol and the implementation of time-outs, incorrect surgical procedures are
      still among the most common types of sentinel events and can have fatal
      consequences. OBJECTIVES: To examine a root cause analysis database for reported
      wrong-side thoracenteses and to determine the contributing factors associated
      with their occurrence. DESIGN, SETTING, AND PARTICIPANTS: We searched the
      National Center for Patient Safety database for wrong-side thoracenteses
      performed in ambulatory clinics and hospital units other than the operating room
      reported from January 1, 2004, through December 31, 2011. MAIN OUTCOMES AND
      MEASURES: Data extracted included patient factors, clinical features, team
      structure and function, adherence to bottom-line patient safety measures,
      complications, and outcomes. RESULTS: Fourteen cases of wrong-side thoracenteses
      are identified. Contributing factors included failure to perform a time-out
      (n=12), missing indication of laterality on the patient's consent form (n=10),
      absence of a site mark on the patient's skin within the sterile field (n=12), and
      absent verification of medical images (n=7). Complications included
      pneumothoraces (n=4), hemorrhage (n=3), and death directly attributable to the
      wrong-side thoracentesis (n=2). Teamwork and communication failure, unawareness
      of existing policy, and a deficit in training and education were the most common
      root causes of wrong-side thoracentesis. CONCLUSIONS AND RELEVANCE: Prevention of
      wrong-site procedures and accompanying patient harm outside the operating room
      requires adherence to the Universal Protocol and time-outs, effective teamwork,
      training and education, mentoring, and patient assessment for early detection of
      complications. The time-outs provide protected time and place for error detection
      and recovery.

PMID- 24920223
TI  - Inner structure of adsorbed ionic microgel particles.
AB  - Microgel particles of cross-linked poly(NIPAM-co-acrylic acid) with different
      acrylic acid contents are investigated in solution and in the adsorbed state. As
      a substrate, silicon with a poly(allylamine hydrochloride) (PAH) coating is used.
      The temperature dependence of the deswelling of the microgel particles was probed
      with atomic force microscopy (AFM). The inner structure of the adsorbed microgel
      particles was detected with grazing incidence small angle neutron scattering
      (GISANS). Small angle neutron scattering (SANS) on corresponding microgel
      suspensions was performed for comparison. Whereas the correlation length of the
      polymer network shows a divergence in the bulk samples, in the adsorbed microgel
      particles it remains unchanged over the entire temperature range. In addition,
      GISANS indicates changes in the particles along the surface normal. This suggests
      that the presence of a solid surface suppresses the divergence of internal
      fluctuations in the adsorbed microgels close to the volume phase transition. 

PMID- 24920224
TI  - Is it feasible to implement enteral nutrition in patients with enteroatmospheric
      fistulae? A single-center experience.
AB  - BACKGROUND: Published experience in feeding patients with enteroatmospheric
      fistulae is scarce. This study aimed to determine if enteral nutrition (EN) could
      be safely delivered in the presence of enteroatmospheric fistula. MATERIALS AND
      METHODS: This is a retrospective descriptive study from a major fistula treatment
      center in China. Medical records of patients who developed enteroatmospheric
      fistulae in the open abdomen after abdominal trauma were reviewed. The timing of
      initiation and achievement of full strength (25 kcal/kg/d) EN after
      enteroatmospheric fistula were noted, as well as the incidence of feeding
      associated complications and weaning of parenteral nutrition (PN). The outcomes
      of open abdomen and enteroatmospheric fistula were also noted. RESULTS: Nine
      patients were included in this study. EN was successfully implemented in all
      patients. The median timing of initiation and achievement of full strength of EN
      after enteroatmospheric fistula was 9 (interquartile range [IQR], 3-22) and 27
      (IQR, 22-43) days, respectively. Feeding-associated complications developed in 1
      (11.1%) patient. All patients were liberated from PN at hospital discharge. Split
      thickness skin grafting was performed in all patients, of whom 5 underwent
      successful delayed abdominal closure, and 4 were awaiting definitive closure.
      Repair or resection of enteroatmospheric fistula occurred in 8 (88.9%) patients.
      CONCLUSION: This study showed that EN could be safely implemented in patients
      with enteroatmospheric fistulae without complicating the treatment of open
      abdomen and enteroatmospheric fistula.

PMID- 24920225
TI  - Exacerbated oxidative stress in the fasting liver according to fuel partitioning.
AB  - Complete starvation may prove lethal due to excessive loss of body proteins.
      However, it is still not completely understood whether responses to food
      deprivation are time-dependently induced or triggered in relation with the
      successive phases of protein sparing and wasting that characterize prolonged
      fasting. As the liver has a wide range of vital functions, we examined the
      hepatic regulatory mechanisms elicited during prolonged fasting. We showed that
      fasting-induced transcriptome/proteome changes occur in close relation with fuel
      partitioning, independently of ATP levels. Omics data suggesting a worsening of
      oxidative stress during the proteolytic stage of fasting were further validated
      using biochemical assays. Low levels of antioxidant factors were indeed
      paralleled by their decreased activity that could be impaired by low NADPH
      levels. Oxidative damage to lipids and proteins was accordingly increased only
      during late fasting. At this stage, the gene/protein expression of several
      chaperones was also repressed. Together with the impairment of metabolic
      achievements, a vicious cycle involving protein misfolding and oxidative stress
      could jeopardize liver function when the proteolytic stage of fasting is reached.
      Thus, monitoring of liver impairments should help to better manage or treat
      catabolic and/or oxidative stress conditions, such as ageing and degeneration. 

PMID- 24920226
TI  - Ln[N(SiMe3 )2 ]3 -catalyzed cross-diinsertion of C=N/C=C into an N=H bond: facile
      synthesis of 1,2,4-trisubstituted imidazoles from propargylamines and nitriles.
AB  - A lanthanide-catalyzed sequential insertion of C?N and C?C into an N?H bond is
      presented. The convenient reaction, which proceeds under mild conditions, is an
      efficient method for preparing 1,2,4-trisubstituted imidazoles directly from
      readily available propargylamines and nitriles. 

PMID- 24920227
TI  - Prolonged hot electron dynamics in plasmonic-metal/semiconductor heterostructures
      with implications for solar photocatalysis.
AB  - Ideal solar-to-fuel photocatalysts must effectively harvest sunlight to generate
      significant quantities of long-lived charge carriers necessary for chemical
      reactions. Here we demonstrate the merits of augmenting traditional
      photoelectrochemical cells with plasmonic nanoparticles to satisfy these daunting
      photocatalytic requirements. Electrochemical techniques were employed to
      elucidate the mechanics of plasmon-mediated electron transfer within Au/TiO2
      heterostructures under visible-light (lambda>515 nm) irradiation in solution.
      Significantly, we discovered that these transferred electrons displayed excited
      state lifetimes two orders of magnitude longer than those of electrons
      photogenerated directly within TiO2 via UV excitation. These long-lived electrons
      further enable visible-light-driven H2 evolution from water, heralding a new
      photocatalytic paradigm for solar energy conversion. 

PMID- 24920228
TI  - Analytical methodology optimization to estimate the content of non-flavonoid
      phenolic compounds in Argentine propolis extracts.
AB  - CONTEXT: Traditionally, the content of total phenolics (flavonoid phenolics (FP)
      and non-flavonoid phenolics (NFP)) and flavonoids (flavone/flavonol and
      flavonone/dihydroflavonol) in propolis has been determined by different
      methodologies. Until now, the percentage of total phenolic (TP) compounds that
      corresponds to FP and NFP, expressed in the same units by a spectrophotometric
      method, has not been determined. OBJECTIVE: The current study proposes a quick
      and simple methodology that separates FP and NFP in propolis samples and
      determines TP, FP, and NFP by the same method. MATERIALS AND METHODS: Propolis
      samples from five Argentine provinces (Tucuman, Santiago del Estero, Salta,
      Misiones, and Jujuy) were used. Extraction of TP from the propolis samples was
      carried out by maceration with 80% ethanol and quantified by Folin-Ciocalteu
      reagent (FC-R). Then, FP was precipitated with formaldehyde in acid medium. After
      centrifugation, NFP were determined in the supernatant using FC-R. FP content was
      calculated as the difference between the content of TP and NFP. The method was
      also validated using commercial flavonoids and chalcones. RESULTS: FP recovery in
      all experiments was between 85.95% and 98.29%. Propolis from Tucuman had
      significantly higher amounts of total phenols than propolis from other provinces.
      SE5 showed higher content of FP (81.52%) followed by SA1 (74.75%). The propolis
      from TUC4, SA4, SE3, and MI showed the lowest FP content and highest content of
      NFP. CONCLUSIONS: This method provides a simple, reliable, and specific
      spectrophotometric assay to estimate the content of NFP, FP, and TP in propolis
      samples.

PMID- 24920229
TI  - Screening compounds of Chinese medicinal herbs anti-Marek's disease virus.
AB  - CONTEXT: Marek's disease (MD) seriously threatens the world poultry industry and
      has resulted in great economic losses. Chinese medicinal herbs are a rich source
      for lead compounds and drug candidates for antiviral treatments. OBJECTIVE: To
      investigate the anti-MDV activity and mechanism of 20 compounds extracted from
      Chinese medicinal herbs. MATERIALS AND METHODS: Antiviral assay, time of addition
      experiments, and virucidal assay were performed on chicken embryo fibroblast
      cells. The 50% cytotoxic concentration and 50% effective concentration were
      determined and, accordingly, selectivity index and inhibition ratio were
      calculated. RESULTS: Antiviral assay showed dipotassium glycyrrhizinate (DG) and
      sodium tanshinone IIA sulfonate (STS) exhibited significantly inhibitory activity
      against MDV in a dose-dependent manner. EC50 of DG and STS were 893.5 +/- 36.99
      ug/mL and 54.82 +/- 2.99 ug/mL, and selective index (SI) were >3.36 and >9.12,
      respectively. Time of addition experiment and virucidal assay demonstrated DG
      inhibited viral replication in the full replication cycle and inactivated MDV
      particles in non-time-dependent manner, but STS interfered with the early stage
      of MDV replication and inactivated MDV particles in a time-dependent manner.
      Moreover, both DG and STS promoted apoptosis of cells infected by MDV. DISCUSSION
      AND CONCLUSION: DG and STS have great potential for developing new anti-MDV drugs
      for clinic application.

PMID- 24920230
TI  - Fusogenic pH sensitive liposomal formulation for rapamycin: improvement of
      antiproliferative effect.
AB  - CONTEXT: Liposomes are increasingly employed to deliver chemotherapeutic agents,
      antisense oligonucleotides, and genes to various therapeutic targets. OBJECTIVE:
      The present investigation evaluates the ability of fusogenic pH-sensitive
      liposomes of rapamycin in increasing its antiproliferative effect on human breast
      adenocarcinoma (MCF-7) cell line. MATERIALS AND METHODS: Cholesterol (Chol) and
      dipalmitoylphosphatidylcholine (DPPC) (DPPC:Chol, 7:3) were used to prepare
      conventional rapamycin liposomes by a modified ethanol injection method.
      Dioleoylphosphatidylethanolamine (DOPE) was used to produce fusogenic and pH
      sensitive properties in liposomes simultaneously (DPPC:Chol:DOPE, 7:3:4.2). The
      prepared liposomes were characterized by their size, zeta potential,
      encapsulation efficiency percent (EE%), and chemical stability during 6 months.
      The antiproliferative effects of both types of rapamycin liposomes (10, 25, and
      50 nmol/L) with optimized formulations were assessed on MCF-7 cells, as cancerous
      cells, and human umbilical vein endothelial cells (HUVEC), as healthy cells,
      employing the diphenyltetrazolium bromide (MTT) assay for 72 h. RESULTS AND
      DISCUSSION: The particle size, zeta potential, and EE% of the liposomes were 165
      +/- 12.3 and 178 +/- 15.4 nm, -39.6 +/- 1.3, and -41.2 +/- 2.1 mV as well as 76.9
      +/- 2.6 and 76.9 +/- 2.6% in conventional and fusogenic pH-sensitive liposomes,
      respectively. Physicochemical stability results indicated that both liposome
      types were relatively stable at 4  degrees C than 25  degrees C. In vitro
      antiproliferative evaluation showed that fusogenic pH-sensitive liposomes had
      better antiproliferative effects on MCF-7 cells compared to the conventional
      liposomes. Conversely, fusogenic pH-sensitive liposomes had less cytotoxicity on
      HUVEC cell line.

PMID- 24920231
TI  - Estonian folk traditional experiences on natural anticancer remedies: from past
      to the future.
AB  - CONTEXT: Despite diagnostic and therapeutic advancements, the burden of cancer is
      still increasing worldwide. Toxicity of current chemotherapeutics to normal cells
      and their resistance to tumor cells highlights the urgent need for new drugs with
      minimal adverse side effects. The use of natural anticancer agents has entered
      into the area of cancer research and increased efforts are being made to isolate
      bioactive products from medicinal plants. OBJECTIVE: To lead the search for
      plants with potential cytotoxic activity, ethnopharmacological knowledge can give
      a great contribution. Therefore, the attention of this review is devoted to the
      natural remedies traditionally used for the cancer treatment by Estonian people
      over a period of almost 150 years. METHODS: Two massive databases, the first one
      stored in the Estonian Folklore Archives and the second one in the electronic
      database HERBA ( http://herba.folklore.ee/ ), containing altogether more than 30
      000 ethnomedicinal texts were systematically reviewed to compile data about the
      Estonian folk traditional experiences on natural anticancer remedies. RESULTS AND
      CONCLUSION: As a result, 44 different plants with potential anticancer properties
      were elicited, 5 of which [Angelica sylvestris L. (Apiaceae), Anthemis tinctoria
      L. (Asteraceae), Pinus sylvestris L. (Pinaceae), Sorbus aucuparia L. (Rosaceae),
      and Prunus padus L. (Rosaceae)] have not been previously described with respect
      to their tumoricidal activities in the scientific literature, suggesting thus the
      potential herbal materials for further investigations of natural anticancer
      compounds.

PMID- 24920232
TI  - Anticancer activity of Cocculus hirsutus against Dalton's lymphoma ascites (DLA)
      cells in mice.
AB  - CONTEXT: Cocculus hirsutus (L.) Diels (Menispermaceae) is used in Indian folk
      system of alternative medicine for rheumatism, eczema, diabetics, inflammation,
      and neuralgia. OBJECTIVE: To evaluate antitumor activities of C. hirsutus in
      vitro and in vivo. MATERIALS AND METHODS: C. hirsutus was successively extracted
      using hexane, petroleum ether, chloroform, ethyl acetate, methanol, and water. In
      vitro cytotoxicity was assessed by the MTT assay. Phytochemical analyses were
      conducted with methanol extract of C. hirsutus (MECH) and in vivo antitumor
      activity was carried out with MECH using Dalton's lymphoma ascites (DLA) mouse
      model. Antioxidant properties were assessed by estimating superoxide dismutase
      (SOD), catalase (CAT), and lipid peroxidation. RESULTS AND DISCUSSION:
      Phytochemical studies indicated a high content of total alkaloid (165.6 mg/100
      g), total phenolic (43.5 GAE mg/g), and total flavanoid (4.97 RE mg/g) in MECH.
      Anti-proliferative activity against the breast cancer cell line MCF-7 showed IC50
      values of 221.5 +/- 16.68, 255 +/- 17.88, 213 +/- 8.4, 147 +/- 7.9, and 229 +/-
      8.02 ug/ml with hexane, petroleum ether, chloroform, ethyl acetate, methanol, and
      aqueous extracts, respectively. A significant (p < 0.01) decrease in packed cell
      volume, viable cell count, and increased lifespan (58 and 77%) was observed.
      Hematological and serum biochemical profiles were restored to normal levels in
      MECH-treated mice. MECH-treated group significantly (p < 0.001) decreased SOD,
      lipid peroxidation, and CAT towards normal. CONCLUSION: C. hirsutus exhibited
      significant in vitro and in vivo antitumor activities that are reasonably
      attributed to endogenous antioxidant mechanisms.

PMID- 24920233
TI  - Prospective neurobiological effects of the aerial and root extracts and some pure
      compounds of randomly selected Scorzonera species.
AB  - CONTEXT: Scorzonera L. species (Asteraceae) are edible and as medicinal plants
      are used for various purposed in folk medicine. OBJECTIVE: The methanol extracts
      of the aerial parts and roots from 27 Scorzonera taxa were investigated for their
      possible neurobiological effects. MATERIALS AND METHODS: Inhibitory potential of
      the Scorzonera species was tested against acetylcholinesterase (AChE),
      butyrylcholinesterase (BChE), and tyrosinase (TYRO) at 100 ug mL(-1) using ELISA
      microtiter assay. Antioxidant activity of the extracts was tested with radical
      scavenging activity, metal-chelation capacity, ferric- (FRAP), and
      phosphomolibdenum-reducing antioxidant power (PRAP) assays. Chlorogenic acid,
      hyperoside, rutin, and scorzotomentosin-4-O-beta-glucoside were also screened in
      the same manner. Total phenol and flavonoid quantification in the extracts were
      determined spectrophotometrically. RESULTS: The aerial parts of Scorzonera
      pisidica (40.25 +/- 0.74%) and chlorogenic acid (46.97 +/- 0.82%) displayed the
      highest TYRO inhibition, while the remaining samples showed only trivial
      inhibition against cholinesterases (2.08 +/- 1.35%-25.32 +/- 1.37%). The same
      extract of S. pisidica was revealed to be the most potent in scavenging of all
      three radicals and FRAP assay. DISCUSSION AND CONCLUSION: Out of 27 taxa, S.
      pisidica, in particular, may deserve further investigation for its
      neuroprotective potential.

PMID- 24920234
TI  - Hypericum perforatum: Influences of the habitat on chemical composition, photo
      induced cytotoxicity, and antiradical activity.
AB  - CONTEXT: Hypericin, isolated from Hypericum perforatum L. and about another 300
      Hypericum species (Guttiferae), is one of the most powerful photosensitizers
      found in nature. OBJECTIVE: The aim of this study was to assess the variability
      of chemical composition and biological activities of four H. perforatum samples,
      collected at different altitudes in the South Apennine of Italy. MATERIALS AND
      METHODS: MTT assay was used to evaluate the antiproliferative activity of
      different samples concentrations (0.6-100 ug/mL) after irradiation at 365 nm. The
      inhibition of nitric oxide production was evaluated after 24 h of incubation
      using the macrophage cell line RAW 264.7 and sample solutions ranging from 12.5
      to 1000 ug/mL. Antioxidant activities were evaluated using 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay and beta-carotene bleaching test (ranges were 12.5
      1000 and 1-400 ug/mL, respectively). Chemical composition was evaluated through
      HPTLC, and different contents of hypericin and rutin have been observed. RESULTS:
      The most phototoxic sample was collected from Zumpano (no. 1 at 370 m), with IC50
      values of 24.61 +/- 0.02 MUg/mL. Sample no. 1 showed also the best radical
      scavenging activity (IC50 value of 9.18 +/- 0.03 MUg/mL) and the best antioxidant
      activity (IC50 value of 10.04 +/- 0.03 MUg/mL after 30 min of incubation). Best
      activity of extract no. 1 was well in accordance with chemical data, including
      the phenolic total content and particular metabolome profile. DISCUSSION AND
      CONCLUSION: This paper confirms the usefulness in maintaining the exploration of
      H. perforatum activities, in order to confirm its potentiality as a multipurpose
      plant.

PMID- 24920235
TI  - Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting
      MAPK and NF-kappaB signaling in activated HMC-1 human mast cells.
AB  - CONTEXT: Caffeic acid phenethyl ester (CAPE), an active component of honeybee
      propolis, is known to have antioxidant, anti-inflammatory, and other beneficial
      medicinal properties. However, the molecular mechanisms underlying its anti
      allergic effects in mast cells are unknown. OBJECTIVE: The purpose of the present
      study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated
      local allergic reaction in animals, as well as to elucidate the effects of CAPE
      on mast cells in vitro. MATERIALS AND METHODS: To investigate the bioactive
      potential of CAPE (10 or 20 uM), HMC-1 cells were stimulated with phorbol 12
      myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the
      presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme
      linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis,
      electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.
      RESULTS: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164
      versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 uM) attenuated PMACI
      stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of
      inflammatory cytokines, such as interleukin (IL)-1beta (4.775 versus 0.713 pg/ml,
      IC50 = 6.67 uM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 uM), and IL-8
      (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 uM) in HMC-1 cells. In activated HMC-1
      cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal
      kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-kappaB
      activation by suppressing IkappaBalpha phosphorylation and its degradation.
      DISCUSSION AND CONCLUSION: Our results indicated that CAPE can modulate mast cell
      mediated allergic disease.

PMID- 24920237
TI  - Enhanced performance of dicationic ionic liquid electrolytes by organic solvents.
AB  - The use of dicationic ionic liquid (DIL) electrolytes in supercapacitors is
      impeded by the slow dynamics of DILs, whereas the addition of organic solvents
      into DIL electrolytes improves ion transport and then enhances the power density
      of supercapacitors. In this work, the influences of organic solvents on the
      conductivity of DILs and the electrical double layer (EDL) of DIL-based
      supercapacitors are investigated using classical molecular dynamics simulation.
      Two types of organic solvents, acetonitrile (ACN) and propylene carbonate (PC),
      were used to explore the effects of different organic solvents on the EDL
      structure and capacitance of DIL/organic solvent-based supercapacitors. Firstly,
      it was found that the conductivity of DIL electrolytes was greatly enhanced in
      the presence of the organic solvent ACN. Secondly, a stronger adsorption of PC on
      graphite results in different EDL structures formed by DIL/ACN and DIL/PC
      electrolytes. The expulsion of co-ions from EDLs was observed in DIL/organic
      solvent electrolytes rather than neat DILs and this feature is more evident in
      DIL/PC. Furthermore, the bell-shaped differential capacitance-electric potential
      curve was not essentially changed by the presence of organic solvents. Comparing
      DIL/organic solvent electrolytes with neat DILs, the capacitance is slightly
      increased by organic solvents, which is in agreement with experimental
      observation. 

PMID- 24920238
TI  - Protein kinase C zeta regulates survivin expression and inhibits apoptosis in
      colon cancer.
AB  - The phosphatidylinositol 3-kinase pathway transduces cell survival signals in
      different malignancies. Protein kinase C zeta (PKCzeta) is one of the molecules
      involved in this pathway. In this study, we investigated the role of PKCzeta in
      apoptosis. Short interfering RNA against PKCzeta (siPKCzeta) sensitized HCT116
      and SW480 colon cancer cells to TRAIL-induced apoptosis. Among anti-apoptotic
      proteins, survivin protein and mRNA expression levels decreased after siPKCzeta
      transfection while protein half-life did not change. The expression levels of
      survivin and PKCzeta were correlated in 18 colon cancer specimens (r=0.72,
      P=3.01x10-4). Chemosensitivity to 5-FU was enhanced by siPKCzeta in HCT116 and
      SW480 cells. These results indicate that PKCzeta regulates survivin expression
      levels and inhibits apoptosis in colon cancer cells. This study provides a
      rationale for targeting PKCzeta in combination with chemotherapy for colon cancer
      treatment.

PMID- 24920239
TI  - Tanshinone IIA induces apoptosis in fibroblast-like synoviocytes in rheumatoid
      arthritis via blockade of the cell cycle in the G2/M phase and a mitochondrial
      pathway.
AB  - Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia
      miltiorrhiza BUNGE, has been documented with anti-tumor, pro-apoptotic, and anti
      inflammatory activities. Salvia miltiorrhiza has long been used to treat
      rheumatoid arthritis (RA). Apoptosis induction of RA-fibroblast-like synoviocytes
      (FLS) was suggested to be a potential therapeutic approach for RA. The aim of
      this study was to investigate whether Tan IIA promotes apoptosis in RA-affected
      FLS. In this study, the viability of an immortalized FLS cell line derived from
      RA patients was assessed by 3-(4,5-dimethylthiazol-2-yl)-5,3-carboxymethoxyphenyl
      2,4-sulfophenyl-2H-tetrazolium (MTS) assay after Tan IIA treatment. Apoptosis was
      measured by terminal deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)
      assay and flow cytometry. Cell cycle was evaluated by flow cytometry. The
      expressions of mitochondrial apoptosis-related molecules, including Bcl-2, Bax,
      mitochondrial cytochrome c (Cyt-c), cytosolic Cyt-c, apoptotic protease
      activating factor 1 (Apaf-1), procaspase-9, procaspase-3, caspase-9, and caspase
      3 were determined by Western blotting. Our data demonstrate that Tan IIA induced
      apoptosis of RA-FLS, blocked the cell cycle in the G2/M phase, and regulated the
      protein expression of Bcl-2, Bax, and Apaf-1, the release of mitochondrial Cyt-c,
      and the activation of caspase-9 and caspase-3. The results support the conclusion
      Tan IIA treatment likely induces apoptosis of RA-FLS through blockade of the cell
      cycle in the G2/M phase and a mitochondrial pathway. These data suggest that Tan
      IIA may have therapeutic potential for RA. 

PMID- 24920240
TI  - Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar
      bodies and stratum corneum barrier lipid organization.
AB  - Classic Refsum disease (RD) is a rare, autosomal recessively-inherited disorder
      of peroxisome metabolism due to a defect in the initial step in the alpha
      oxidation of phytanic acid (PA), a C16 saturated fatty acid with four methyl side
      groups, which accumulates in plasma and lipid enriched tissues (please see van
      den Brink and Wanders, Cell Mol Life Sci 63:1752-1765, 2006). It has been
      proposed that the disease complex in RD is in part due to the high affinity of
      phytanic acid for retinoid X receptors and peroxisome proliferator-activated
      receptors. Structurally, epidermal hyperplasia, increased numbers of cornified
      cell layers, presence of cells with lipid droplets in stratum basale and
      reduction of granular layer to a single layer have been reported by Blanchet
      Bardon et al. (The ichthyoses, SP Medical & Scientific Books, New York, pp 65-69,
      1978). However, lamellar body (LB) density and secretion were reportedly normal.
      We recently examined biopsies from four unrelated patients, using both OsO4 and
      RuO4 post-fixation to evaluate the barrier lipid structural organization.
      Although lamellar body density appeared normal, individual organelles often had
      distorted shape, or had non-lamellar domains interspersed with lamellar
      structures. Some of the organelles seemed to lack lamellar contents altogether,
      showing instead uniformly electron-dense contents. In addition, we also observed
      mitochondrial abnormalities in the nucleated epidermis. Stratum granulosum
      stratum corneum junctions also showed co-existence of non-lamellar and lamellar
      domains, indicative of lipid phase separation. Also, partial detachment or
      complete absence of corneocyte lipid envelopes (CLE) was seen in the stratum
      corneum of all RD patients. In conclusion, abnormal LB contents, resulting in
      defective lamellar bilayers, as well as reduced CLEs, likely lead to impaired
      barrier function in RD. 

PMID- 24920241
TI  - Outstanding effects on antithrombin activity of modified TBA diastereomers
      containing an optically pure acyclic nucleotide analogue.
AB  - Herein, we report optically pure modified acyclic nucleosides as ideal probes for
      aptamer modification. These new monomers offer unique advantages in exploring the
      role played in thrombin inhibition by a single residue modification at key
      positions of the TBA structure. 

PMID- 24920242
TI  - The effects of an energy efficiency retrofit on indoor air quality.
AB  - To investigate the impacts of an energy efficiency retrofit, indoor air quality
      and resident health were evaluated at a low-income senior housing apartment
      complex in Phoenix, Arizona, before and after a green energy building renovation.
      Indoor and outdoor air quality sampling was carried out simultaneously with a
      questionnaire to characterize personal habits and general health of residents.
      Measured indoor formaldehyde levels before the building retrofit routinely
      exceeded reference exposure limits, but in the long-term follow-up sampling,
      indoor formaldehyde decreased for the entire study population by a statistically
      significant margin. Indoor PM levels were dominated by fine particles and showed
      a statistically significant decrease in the long-term follow-up sampling within
      certain resident subpopulations (i.e. residents who report smoking and residents
      who had lived longer at the apartment complex). 

PMID- 24920243
TI  - Deciphering the language of plant communication: volatile chemotypes of
      sagebrush.
AB  - Volatile communication between sagebrush (Artemisia tridentata) individuals has
      been found previously to reduce herbivory and to be more effective between
      individuals that are genetically identical or related relative to between
      strangers. The chemical nature of the cues involved in volatile communication
      remains unknown for this and other systems. We collected headspace volatiles from
      sagebrush plants in the field and analyzed these using GC-MS. Volatile profiles
      were highly variable among individuals, but most individuals could be
      characterized as belonging to one of two chemotypes, dominated by either thujone
      or camphor. Analyses of parents and offspring revealed that chemotypes were
      highly heritable. The ecological significance of chemotypes and the genetic
      mechanisms that control them remain poorly understood. However, we found that
      individuals of the same chemotype communicated more effectively and experienced
      less herbivory than individuals of differing chemotypes. Plants may use
      chemotypes to distinguish relatives from strangers. 

PMID- 24920244
TI  - Vasohibin-2 promotes proliferation in human breast cancer cells via upregulation
      of fibroblast growth factor-2 and growth/differentiation factor-15 expression.
AB  - Vasohibin-2 (VASH2) is an angiogenic factor, and has been previously reported to
      be a cancer-related gene, with cytoplasmic and karyotypic forms. In the current
      study VASH2 expression in human breast cancer tissue and adjacent non-cancerous
      tissue was investigated with immunohistochemistry. MCF-7 and BT474 human breast
      cancer cells were transfected with lentiviral constructs to generate in vitro
      VASH2 overexpression and knockdown models. In addition, BALB/cA nude mice were
      inoculated subcutaneously with transfected cells to generate in vivo models of
      VASH2 overexpression and knockdown. The effect of VASH2 on cell proliferation was
      investigated using a bromodeoxyuridine assay in vitro and immunohistochemistry of
      Ki67 in xenograft tumors. Growth factors were investigated using a human growth
      factor array, and certain factors were further confirmed by an immunoblot. The
      results indicated that the expression level of cytoplasmic VASH2 was higher in
      breast cancer tissues with a Ki67 (a proliferation marker) level of >=14%,
      compared with tissues with a Ki67 level of <14%. VASH2 induced proliferation in
      vitro and in vivo. Four growth factors activated by VASH2 were identified as
      follows: Fibroblast growth factor 2 (FGF2), growth/differentiation factor-15
      (GDF15), insulin-like growth factor-binding protein (IGFBP)3 and IGFBP6. FGF2 and
      GDF15 may contribute to VASH2-induced proliferation. The current study identified
      a novel role for VASH2 in human breast cancer, and this knowledge suggests that
      VASH2 may be a novel target in breast cancer treatment. 

PMID- 24920245
TI  - A novel homozygous stop-codon mutation in human HFE responsible for nonsense
      mediated mRNA decay.
AB  - HFE-hemochromatosis (HH) is an autosomal disease characterized by excessive iron
      absorption. Homozygotes for H63D variant, and still less H63D heterozygotes,
      generally do not express HH phenotype. The data collected in our previous study
      in the province of Matera (Basilicata, Italy) underlined that some H63D carriers
      showed altered iron metabolism, without additional factors. In this study, we
      selected a cohort of 10/22 H63D carriers with severe biochemical iron overload
      (BIO). Additional analysis was performed for studying HFE exons, exon-intron
      boundaries, and untranslated regions (UTRs) by performing DNA extraction, PCR
      amplification and sequencing. The results showed a novel substitution
      (NM_000410.3:c.847C>T) in a patient exon 4 (GenBankJQ478433); it introduces a
      premature stop-codon (PTC). RNA extraction and reverse-transcription were also
      performed. Quantitative real-time PCR was carried out for verifying if our
      aberrant mRNA is targeted for nonsense-mediated mRNA decay (NMD); we observed
      that patient HFE mRNA was expressed much less than calibrator, suggesting that
      the mutated HFE protein cannot play its role in iron metabolism regulation,
      resulting in proband BIO. Our finding is the first evidence of a variation
      responsible for a PTC in iron cycle genes. The genotype-phenotype correlation
      observed in our cases could be related to the additional mutation. 

PMID- 24920246
TI  - Risk for Child Maltreatment Among Infants Discharged From a Neonatal Intensive
      Care Unit: A Sibling Comparison.
AB  - Studies suggest that neonatal illness may cause increased risk for child
      maltreatment (CM), but these findings may be biased by observed and unobserved
      confounding factors (social, family, and maternal characteristics) including
      increased surveillance by health care providers. This study expands on previous
      research by examining and controlling for these potential study biases and
      confounders using a sibling discordance retrospective cohort study design.
      Infants born in a Level IV neonatal intensive care unit (NICU) were matched with
      non-NICU born sibling controls. Cox proportional hazard models with shared
      frailty terms were used to account for clustering and heterogeneity in CM
      survival time (time to CM event). Potentially key covariates were selected using
      the directed acyclic graph approach, and surveillance reports were identified and
      systematically included or excluded from analyses. Managing these sources of bias
      reduced but did not eliminate the association between neonatal illness and CM
      report risk. Risk was especially high during the first year of the NICU infant's
      life and among families with multiple well-known CM risk factors.

PMID- 24920247
TI  - Evidence Summarized in Attorneys' Closing Arguments Predicts Acquittals in
      Criminal Trials of Child Sexual Abuse.
AB  - Evidence summarized in attorney's closing arguments of criminal child sexual
      abuse cases (N = 189) was coded to predict acquittal rates. Ten variables were
      significant bivariate predictors; five variables significant at p < .01 were
      entered into a multivariate model. Cases were likely to result in an acquittal
      when the defendant was not charged with force, the child maintained contact with
      the defendant after the abuse occurred, or the defense presented a hearsay
      witness regarding the victim's statements, a witness regarding the victim's
      character, or a witness regarding another witnesses' character (usually the
      mother). The findings suggest that jurors might believe that child molestation is
      akin to a stereotype of violent rape and that they may be swayed by defense
      challenges to the victim's credibility and the credibility of those close to the
      victim.

PMID- 24920248
TI  - On the relationships between commercial sexual exploitation/prostitution,
      substance dependency, and delinquency in youthful offenders.
AB  - Researchers have consistently linked commercial sexual exploitation (CSE) of
      youth and involvement in prostitution with substance dependency and delinquency.
      Yet, important questions remain regarding the directionality and mechanisms
      driving this association. Utilizing a sample of 114 CSE/prostituted youth
      participating in the Pathways to Desistance study-a longitudinal investigation of
      the transition from adolescence to adulthood among serious adolescent offenders
      the current study examined key criminal career parameters of CSE/prostitution
      including age of onset and rate of recurrence. Additionally, structural equation
      modeling (SEM) was used to explore concurrent associations and causal links
      between CSE/prostitution and drug involvement. Findings show a general sequential
      pattern of the ages of onset with substance use and selling drugs occurring prior
      to CSE/prostitution, evidence that a small group with chronic CSE/prostitution
      account for the majority of CSE/prostitution occurrences, and high rates of
      repeated CSE/prostitution. SEM results suggest CSE/prostituted youth persist in
      drug involvement from year to year but infrequently experience perpetuation of
      CSE/prostitution from year to year. Concurrent associations between
      CSE/prostitution and drug involvement were found across the length of the study.
      Additionally, drug involvement at one year was linked to CSE/prostitution during
      the subsequent year during early years of the study. 

PMID- 24920249
TI  - Mental health outcomes in emerging adults exposed to childhood maltreatment: the
      moderating role of stress reactivity.
AB  - Childhood maltreatment is an established risk factor for varying configurations
      of psychological problems in emerging adulthood. The current study tested
      associations between childhood maltreatment, cortisol reactivity, and current
      mental health symptoms in emerging adulthood. Eighty-eight participants (aged 18
      22) completed measures of childhood maltreatment and current internalizing and
      externalizing symptoms and participated in a 10-min conflict role-play task.
      Salivary cortisol was sampled throughout the task, and a residualized change
      score between baseline and peak time points was computed to capture reactivity.
      Results from robust regression analyses indicated that cortisol reactivity
      moderated the association between childhood maltreatment and mental health
      symptoms as hypothesized. Childhood maltreatment was related to greater
      internalizing problems among participants with higher cortisol reactivity,
      whereas maltreatment was associated with greater externalizing problems among
      participants who exhibited lower cortisol reactivity. Results suggest that
      patterns of cortisol reactivity in emerging adulthood may help elucidate mental
      health outcomes associated with childhood maltreatment. 

PMID- 24920250
TI  - Maltreatment histories of foster youth exiting out-of-home care through
      emancipation: a latent class analysis.
AB  - Little is known about maltreatment among foster youth transitioning to adulthood.
      Multiple entries into out-of-home care and unsuccessful attempts at reunification
      may nevertheless reflect extended exposure to chronic maltreatment and multiple
      types of victimization. This study used administrative data from the Illinois
      Department of Children and Family Services to identify all unduplicated
      allegations of maltreatment in a cohort of 801 foster youth transitioning to
      adulthood in the state of Illinois. A latent variable modeling approach generated
      profiles of maltreatment based on substantiated and unsubstantiated reports of
      maltreatment taken from state administrative data. Four indicators of
      maltreatment were included in the latent class analysis: multiple types of
      maltreatment, predominant type of maltreatment, chronicity, and number of
      different perpetrators. The analysis identified four subpopulations of foster
      youth in relation to maltreatment. Study findings highlight the heterogeneity of
      maltreatment in the lives of foster youth transitioning to adulthood and draw
      attention to a need to raise awareness among service providers to screen for
      chronic maltreatment and multiple types of victimization. 

PMID- 24920251
TI  - Biocontrol agents-mediated suppression of oxalic acid induced cell death during
      Sclerotinia sclerotiorum-pea interaction.
AB  - Oxalic acid (OA) is an important pathogenic factor during early Sclerotinia
      sclerotiorum-host interaction and might work by reducing hydrogen peroxide
      production (H2 O2 ). In the present investigation, oxalic acid-induced cell death
      in pea was studied. Pea plants treated with biocontrol agents (BCAs) viz.,
      Pseudomonas aeruginosa PJHU15, Bacillus subtilis BHHU100, and Trichoderma
      harzianum TNHU27 either singly and/or in consortium acted on S. sclerotiorum
      indirectly by enabling plants to inhibit the OA-mediated suppression of oxidative
      burst via induction of H2 O2 . Our results showed that BCA treated plants upon
      treatment with culture filtrate of the pathogen, conferred the resistance via.
      significantly decreasing relative cell death of pea against S. sclerotiorum
      compared to control plants without BCA treatment but treated with the culture
      filtrate of the pathogen. The results obtained from the present study indicate
      that the microbes especially in consortia play significant role in protection
      against S. sclerotiorum by modulating oxidative burst and partially enhancing
      tolerance by increasing the H2 O2 generation, which is otherwise suppressed by OA
      produced by the pathogen. 

PMID- 24920252
TI  - Noise from total hip replacements: a case-controlled study.
AB  - OBJECTIVES: Our study aimed to examine not only the incidence but also the impact
      of noise from two types of total hip replacement articulations: ceramic-on
      ceramic and ceramic-on-polyethylene. METHODS: We performed a case-controlled
      study comparing subjective and objective questionnaire scores of patients
      receiving a ceramic-on-ceramic or a ceramic-on-polyethylene total hip replacement
      by a single surgeon. RESULTS: There was a threefold higher incidence of noise
      from patients in the ceramic-on-ceramic group compared with the control group.
      The impact of this noise was significant for patients both subjectively and
      objectively. CONCLUSIONS: This study reports a high patient impact of noise from
      ceramic-on-ceramic total hip replacements. This has led to a change in practice
      by the principal author. Cite this article: Bone Joint Res 2014;3:183-6.

PMID- 24920254
TI  - Unprecedented cobalt-catalyzed isomerization reactions to single skipped 2,4,7
      trienes applied in the synthesis of urushiol.
AB  - The cobalt-catalyzed isomerization of 1,3-dienes to 2Z,4E-dienes was realized for
      the very challenging substrates with an additional double bond in the side chain.
      An isomerization to the conjugated 3,5,7-triene derivative was not observed,
      which is in stark contrast to observations with many other isomerization
      catalysts. Accordingly, the synthesis of the natural product urushiol, which has
      a sensitive 2Z,4E,7Z-triene subunit in the side chain, was investigated. The O
      protected urushiol derivative was generated selectively without isomerization to
      the conjugated 3,5,7-triene or Z/E-isomerization of the double bond at position
      7. 

PMID- 24920255
TI  - Effect of bioactive coils on endovascular treatment outcomes for intracranial
      aneurysms.

PMID- 24920253
TI  - Molecular analysis of beta-lactamase genes to understand their differential
      expression in strains of Yersinia enterocolitica biotype 1A.
AB  - Beta-lactams are used as major therapeutic agents against a number of infectious
      agents. Due to widespread use of beta-lactams, beta-lactamases have evolved at a
      rapid pace leading to treatment failures. Yersinia enterocolitica causes many
      gastrointestinal problems. It is an extremely heterogeneous species comprising
      more than fifty serotypes and six biotypes which differ in their ecological
      niches, geographical distribution and pathogenic potential. Though biotype 1A
      strains have been associated with outbreaks of Yersiniosis, there has been a
      controversy regarding their pathogenicity. The strains of Y. enterocolitica
      isolated from India belonged to biotype 1A and possessed genes for two beta
      lactamases namely, blaA and blaB. An earlier study by us reported differential
      expression of blaA by strains of Y. enterocolitica biotype 1A. The present study
      has been carried out to understand the molecular bases which regulate the
      expression of blaA in Y. enterocolitica biotype 1A. We concluded that six types
      of blaA variants were present in strains of biotype 1A. Neither amino acid
      substitutions in blaA nor mutations in promoter regions of blaA contributed to
      differential expression of blaA in Y. enterocolitica biotype 1A. Rather, the
      secondary structures attained by mRNA of blaA might underlie the differential
      expression of blaA in Y. enterocolitica. 

PMID- 24920256
TI  - A population of patient-specific adult acquired flatfoot deformity models before
      and after surgery.
AB  - Following IRB approval, a cohort of 3-D rigid-body computational models was
      created from submillimeter MRIs of clinically diagnosed Adult Acquired Flatfoot
      Deformity patients and employed to investigate postoperative foot/ankle function
      and surgical effect during single-leg stance. Models were constrained through
      physiologic joint contact, passive soft-tissue tension, active muscle force, full
      body weight, and without idealized joints. Models were validated against patient
      matched controls using clinically utilized radiographic angle and distance
      measures and plantar force distributions in the medial forefoot, lateral
      forefoot, and hindfoot. Each model further predicted changes in strain for the
      spring ligament, deltoid ligament, and plantar fascia, as well as joint contact
      loads for three midfoot joints, the talonavicular, navicular-1st cuneiform, and
      calcaneocuboid. Radiographic agreement ranged across measures, with average
      absolute deviations of <5 degrees  and <4 mm indicating generally good agreement.
      Postoperative plantar force loading in patients and models was reduced for the
      medial forefoot and hindfoot concomitant with increases in the lateral forefoot.
      Model predicted reductions in medial soft-tissue strain and increases in lateral
      joint contact load were consistent with in vitro observations and elucidate the
      biomechanical mechanisms of repair. Thus, validated rigid-body models offer
      promise for the investigation of foot/ankle kinematics and biomechanical
      behaviors that are difficult to measure in vivo. 

PMID- 24920257
TI  - A headform for testing helmet and mouthguard sensors that measure head impact
      severity in football players.
AB  - A headform is needed to validate and compare helmet- and mouthguard-based sensors
      that measure the severity and direction of football head impacts. Our goal was to
      quantify the dynamic response of a mandibular load-sensing headform (MLSH) and to
      compare its performance and repeatability to an unmodified Hybrid III headform.
      Linear impactors in two independent laboratories were used to strike each
      headform at six locations at 5.5 m/s and at two locations at 3.6 and 7.4 m/s.
      Impact severity was quantified using peak linear acceleration (PLA) and peak
      angular acceleration (PAA), and direction was quantified using the azimuth and
      elevation of the PLA. Repeatability was quantified using coefficients of
      variation (COV) and standard deviations (SD). Across all impacts, PLA was 1.6+/
      1.8 g higher in the MLSH than in the Hybrid III (p=0.002), but there were no
      differences in PAA (p=0.25), azimuth (p=0.43) and elevation (p=0.11). Both
      headforms exhibited excellent or acceptable repeatability for PLA (HIII:COV=2.1+/
      0.8%, MLSH:COV=2.0+/-1.2%, p=0.98), but site-specific repeatability ranging from
      excellent to poor for PAA (HIII:COV=7.2+/-4.0%, MLSH:COV=8.3+/-5.8%, p=0.58).
      Direction SD were generally <1 degrees  and did not vary between headforms.
      Overall, both headforms are similarly suitable for validating PLA in sensors that
      measure head impact severity in football players, however their utility for
      validating sensor PAA values varies with impact location.

PMID- 24920258
TI  - Carbonyl compounds and dissolved organic carbon in rainwater of an urban
      atmosphere.
AB  - This study investigates the occurrence of carbonyl compounds in rainwater at the
      city of Thessaloniki, Northern Greece. The concentrations of carbonyl compounds
      (as sum of 14 compounds) ranged from 21.8 to 592 MUg/L, mean concentration 119
      MUg/L. Formaldehyde, acetaldehyde, hexanal, glyoxal, and methylglyoxal were the
      dominant compounds. DOC concentrations in rainwater ranged from 0.46 to 21.3
      mg/L. UV-Vis and fluorescence spectra characteristics showed variation among rain
      events. Carbonyl compounds were negatively correlated with temperature exhibited
      relatively higher concentrations in cold season. They also influenced by storm
      origin with higher concentrations under terrestrial air masses. Calm conditions
      enhance the concentrations of DOC. Wash out is an effective removal mechanism of
      DOC.

PMID- 24920259
TI  - Determination of nickel in blood and serum samples of oropharyngeal cancer
      patients consumed smokeless tobacco products by cloud point extraction coupled
      with flame atomic absorption spectrometry.
AB  - Oropharyngeal cancer is a significant public health issue in the world. The
      incidence of oropharyngeal cancer has been increased among people who have habit
      of chewing smokeless tobacco (SLT) in Pakistan. The aim of present study was to
      evaluate the concentration of nickel (Ni) in biological samples (whole blood,
      serum) of oral (n = 95) and pharyngeal (n = 84) male cancer patients. For
      comparison purposes, the biological samples of healthy age-matched referents (n =
      150), who consumed and did not consumed SLT products, were also analyzed for Ni
      levels. As the Ni level is very low in biological samples, a preconcentration
      procedure has been developed, prior to analysis of analyte by flame atomic
      absorption spectrometry (FAAS). The Ni in acid-digested biological samples was
      complexed with ammonium pyrrolidinedithio carbamate (APDC), and a resulted
      complex was extracted in a surfactant Triton X-114. Acidic ethanol was added to
      the surfactant-rich phase prior to its analysis by FAAS. The chemical variables,
      such as pH, amounts of reagents (APDC, Triton X-114), temperature, incubation
      time, and sample volume were optimized. The resulted data indicated that
      concentration of Ni was higher in blood and serum samples of cancer patients as
      compared to that of referents who have or have not consumed different SLT
      products (p = 0.012-0.001). It was also observed that healthy referents who
      consumed SLT products have two to threefold higher levels of Ni in both
      biological samples as compared to those who were not chewing SLT products (p <
      0.01).

PMID- 24920260
TI  - Improving nitrogen removal using a fuzzy neural network-based control system in
      the anoxic/oxic process.
AB  - Due to the inherent complexity, uncertainty, and posterity in operating a
      biological wastewater treatment process, it is difficult to control nitrogen
      removal in the biological wastewater treatment process. In order to cope with
      this problem and perform a cost-effective operation, an integrated neural-fuzzy
      control system including a fuzzy neural network (FNN) predicted model for
      forecasting the nitrate concentration of the last anoxic zone and a FNN
      controller were developed to control the nitrate recirculation flow and realize
      nitrogen removal in an anoxic/oxic (A/O) process. In order to improve the network
      performance, a self-learning ability embedded in the FNN model was emphasized for
      improving the rule extraction performance. The results indicate that reasonable
      forecasting and control performances had been achieved through the developed
      control system. The effluent COD, TN, and the operation cost were reduced by
      about 14, 10.5, and 17 %, respectively.

PMID- 24920262
TI  - Spatial distribution, potential risk assessment, and source apportionment of
      polycyclic aromatic hydrocarbons (PAHs) in sediments of Lake Chaohu, China.
AB  - Twenty-nine sediment samples were collected from Lake Chaohu, a shallow eutrophic
      lake in Eastern China, and were analyzed for 15 priority polycyclic aromatic
      hydrocarbons (PAHs) to determine the spatial distribution and exposure risks of
      PAHs. Three receptor models, the principal component analysis-multiple linear
      regression (PCA-MLR) model, the positive matrix factorization (PMF) model, and
      the Unmix model, were used in combination with the PAHs diagnostic ratios to
      investigate the potential source apportionment of PAHs. A clear gradient in the
      spatial distribution and the potential toxicity of PAHs was observed from west to
      east in the sediments of Lake Chaohu. ?15PAH concentrations and the TEQ were in
      the range of 80.82-30 365.01 ng g(-1) d.w. and 40.77-614.03, respectively. The
      highest values of the aforementioned variables were attributed to urban
      industrial pollution sources in the west lake region, and the levels decreased
      away from the river inlets. The three different models yielded excellent
      correlation coefficients between the predicted and measured levels of the 15 PAH
      compounds. Similarly, source apportionment results were derived from the three
      receptor models and the PAH diagnostic ratios, suggesting that the highest
      contribution to the PAHs was from coal combustion and wood combustion, followed
      by vehicular emissions. The PMF model yielded the following contributions to the
      PAHs from gasoline combustion, diesel combustion, unburned petroleum emissions,
      and wood combustion: 34.49, 24.61, 16.11, 13.01, and 11.78 %, respectively. The
      PMF model produced more detailed source apportionment results for the PAHs than
      the PCA-MLR and Unmix models.

PMID- 24920261
TI  - Expression of biotransformation and oxidative stress genes in the giant
      freshwater prawn Macrobrachium rosenbergii exposed to chlordecone.
AB  - Chlordecone is a persistent organochlorine pesticide widely used between 1972 and
      1993 in the French West Indies to control the root borer in banana fields.
      Chlordecone use resulted in long-term pollution of soils, contamination of
      waters, of aquatic organisms, and of fields. Chlordecone is known to be
      neurotoxic, to increase prostate cancer, and to have negative effects on
      cognitive and motor development during infancy. In Guadeloupe, most of the
      freshwater species living in contaminated rivers exceed the French legal limit of
      20 MUg.kg(-1) wet weight. In the present study, we chose a transcriptomic
      approach to study the cellular effects of chlordecone in the giant freshwater
      prawn Macrobrachium rosenbergii, an important economical species in Guadeloupe.
      Quantitative PCR revealed an induction of genes involved in defense mechanism
      against oxidative stress (catalase and selenium-dependent glutathione peroxidase)
      in prawns exposed to low environmental concentrations of chlordecone after 12 and
      24 h of exposure. In prawns reared in a contaminated farm, transcription of genes
      involved in the biotransformation process (cytochrome P450 and glutathione-S
      transferase (GST)) were induced after 8 days of exposure. Our results provide
      information on the mechanims of defense induced by chlordecone in aquatic
      crustacean species. This gene expression study of selected genes should be
      further strengthened by proteomic analyses and enzymatic activity assays to
      confirm the response of these biomarkers of stress in crustaceans and to give new
      insights into the mechanism of toxicity by chlordecone. 

PMID- 24920263
TI  - Sodium arsenate induce changes in fatty acids profiles and oxidative damage in
      kidney of rats.
AB  - Six groups of rats (n = 10 per group) were exposed to 1 and 10 mg/l of sodium
      arsenate for 45 and 90 days. Kidneys from treated groups exposed to arsenic
      showed higher levels of trans isomers of oleic and linoleic acids as trans C181n
      9, trans C18:1n-11, and trans C18:2n-6 isomers. However, a significant decrease
      in eicosenoic (C20:1n-9) and arachidonic (C20:4n-6) acids were observed in
      treated rats. Moreover, the "Delta5 desaturase index" and the
      saturated/polyunsaturated fatty acids ratio were increased. There was a
      significant increase in the level of malondialdehyde at 10 mg/l of treatment and
      in the amount of conjugated dienes after 90 days (p < 0.05). Significant kidney
      damage was observed at 10 mg/l by increase of plasma marker enzymes. Histological
      studies on the ultrastructure changes of kidney supported the toxic effect of
      arsenate exposure. Arsenate intoxication activates significantly the superoxide
      dismutase at 10 mg/l for 90 days, whereas the catalase activity was markedly
      inhibited in all treated groups (p < 0.05). In addition, glutathione peroxidase
      activity was significantly increased at 45 days and dramatically declined after
      90 days at 10 mg/l (p < 0.05). A significant increase in the level of glutathione
      was marked for the groups treated for 45 and 90 days at 1 mg/l followed by a
      significant decrease for rats exposed to 10 mg/l for 90 days. An increase in the
      level of protein carbonyl was observed in all treated groups (p < 0.05). In
      conclusion, the present study provides evidence for a direct effect of arsenate
      on fatty acid (FA) metabolism which concerns the synthesis pathway of n-6
      polyunsaturated fatty acids and leads to an increase in the trans FAs isomers.
      Therefore, FA-induced arsenate kidney damage could contribute to trigger kidney
      cancer.

PMID- 24920264
TI  - Effect of water current on the distribution of polycyclic aromatic hydrocarbons,
      heavy metals and benthic diatom community in sediments of Haihe estuary, China.
AB  - The pollution loads continuously increased in Haihe estuary, of Tianjin, China,
      due to intensive human activities, especially the construction of the Haihe Gate
      and Lingang Industrial Area. In 2011, hydrological variability in Haihe estuary
      was investigated and sediments were collected. Total organic carbon (TOC),
      particle size, total polycyclic aromatic hydrocarbons (SigmaPAHs), heavy metals
      (Cd, Cr, Cu, Ni, Pb, and Zn), and benthic diatom community were analyzed. The
      highest concentrations of SigmaPAHs and heavy metals were found near the Haihe
      Gate. The Shannon diversity index and the relative abundance of Coscinodiscus
      perforatus (RC) indicated a decreasing trend seaward. Results of Pearson
      correlation analysis illustrated significant relations between water current
      velocity and SigmaPAHs (p < 0.01), Cr (p < 0.05), and RC (p < 0.05). Path
      analysis further indicated that water current played an important role in the
      distribution of PAH, Cr, and RC.

PMID- 24920267
TI  - Urinary ACE2 in healthy adults and patients with uncomplicated type 1 diabetes.
AB  - Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be
      renoprotective. We determined whether urinary ACE2 enzyme activity and protein
      levels (ELISA), as well as angiotensinogen and ACE, are elevated during clamped
      euglycemia (4-6 mmol.L(-1)) in patients with uncomplicated type 1 diabetes (T1D,
      n = 58) compared with normoglycemic controls (n = 21). We also measured the
      effect of clamped hyperglycemia (9-11 mmol.L(-1)) on each urinary factor in T1D
      patients. Urinary ACE2 activity and protein levels were higher during clamped
      euglycemia in T1D compared with the controls (p < 0.0001). In contrast, urinary
      angiotensinogen levels (p = 0.27) and ACE excretion (p = 0.68) did not differ. In
      response to clamped hyperglycemia in T1D, urinary ACE2 protein decreased (p <
      0.0001), whereas urinary ACE2 activity as well as angiotensinogen and ACE levels
      remained unchanged. Urinary ACE2 activity and protein expression are increased in
      T1D patients prior to the onset of clinical complications. Further work is
      required to determine the functional role of urinary ACE2 in early T1D. 

PMID- 24920265
TI  - Phylogenetic analysis of the microbial community in hypersaline petroleum
      produced water from the Campos Basin.
AB  - In this work the archaea and eubacteria community of a hypersaline produced water
      from the Campos Basin that had been transported and discharged to an onshore
      storage facility was evaluated by 16S recombinant RNA (rRNA) gene sequence
      analysis. The produced water had a hypersaline salt content of 10 (w/v), had a
      carbon oxygen demand (COD) of 4,300 mg/l and contains phenol and other aromatic
      compounds. The high salt and COD content and the presence of toxic phenolic
      compounds present a problem for conventional discharge to open seawater. In
      previous studies, we demonstrated that the COD and phenolic content could be
      largely removed under aerobic conditions, without dilution, by either addition of
      phenol degrading Haloarchaea or the addition of nutrients alone. In this study
      our goal was to characterize the microbial community to gain further insight into
      the persistence of reservoir community members in the produced water and the
      potential for bioremediation of COD and toxic contaminants. Members of the
      archaea community were consistent with previously identified communities from
      mesothermic reservoirs. All identified archaea were located within the phylum
      Euryarchaeota, with 98 % being identified as methanogens while 2 % could not be
      affiliated with any known genus. Of the identified archaea, 37 % were identified
      as members of the strictly carbon-dioxide-reducing genus Methanoplanus and 59 %
      as members of the acetoclastic genus Methanosaeta. No Haloarchaea were detected,
      consistent with the need to add these organisms for COD and aromatic removal.
      Marinobacter and Halomonas dominated the eubacterial community. The presence of
      these genera is consistent with the ability to stimulate COD and aromatic removal
      with nutrient addition. In addition, anaerobic members of the phyla Thermotogae,
      Firmicutes, and unclassified eubacteria were identified and may represent
      reservoir organisms associated with the conversion hydrocarbons to methane.

PMID- 24920268
TI  - Tree mineral nutrition is deteriorating in Europe.
AB  - The response of forest ecosystems to increased atmospheric CO2 is constrained by
      nutrient availability. It is thus crucial to account for nutrient limitation when
      studying the forest response to climate change. The objectives of this study were
      to describe the nutritional status of the main European tree species, to identify
      growth-limiting nutrients and to assess changes in tree nutrition during the past
      two decades. We analysed the foliar nutrition data collected during 1992-2009 on
      the intensive forest monitoring plots of the ICP Forests programme. Of the 22
      significant temporal trends that were observed in foliar nutrient concentrations,
      20 were decreasing and two were increasing. Some of these trends were alarming,
      among which the foliar P concentration in F. sylvatica, Q. Petraea and P.
      sylvestris that significantly deteriorated during 1992-2009. In Q. Petraea and P.
      sylvestris, the decrease in foliar P concentration was more pronounced on plots
      with low foliar P status, meaning that trees with latent P deficiency could
      become deficient in the near future. Increased tree productivity, possibly
      resulting from high N deposition and from the global increase in atmospheric CO2,
      has led to higher nutrient demand by trees. As the soil nutrient supply was not
      always sufficient to meet the demands of faster growing trees, this could partly
      explain the deterioration of tree mineral nutrition. The results suggest that
      when evaluating forest carbon storage capacity and when planning to reduce CO2
      emissions by increasing use of wood biomass for bioenergy, it is crucial that
      nutrient limitations for forest growth are considered.

PMID- 24920269
TI  - Monitoring the AML1/ETO fusion transcript to predict outcome in childhood acute
      myeloid leukemia.
AB  - BACKGROUND: To determine the prognostic significance of the detection of the
      minimal residual disease (MRD) in children with AML1/ETO AML, we compared the
      results of reverse-transcription polymerase chain reaction (RT-PCR) and
      quantitative reverse-transcription polymerase chain reaction (RQ-PCR). PROCEDURE:
      Between January 2006 and February 2013, 70 patients (<=16 years of age) with
      AML1/ETO AML were included in our study. Bone marrow samples were evaluated using
      by both RT-PCR and RQ-PCR assays. AML1/ETO transcripts were normalized to 10(5)
      ABL copies. RESULTS: When treated with fewer than four courses of therapy, no
      association was found between positive RT-PCR results and relapse. After four
      courses of therapy, a positive RT-PCR result was correlated with a probability of
      relapse. After induction chemotherapy, a >1.8 log reduction in AML1/ETO
      transcripts in BM determined by RQ-PCR may represent a subgroup of patients at
      low risk for relapse. MRD levels after consolidation (Courses 2 and 3) were also
      informative. CONCLUSION: Both RT-PCR and RQ-PCR can be used to detect MRD in
      childhood AML1/ETO AML. RQ-PCR can identify patients who are at high risk of
      relapse earlier than can RT-PCR.

PMID- 24920270
TI  - Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in
      mildly hypercholesterolemic adults: a double-blinded, randomized, placebo
      controlled study.
AB  - BACKGROUND: High level of serum cholesterol is considered to be a major risk
      factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo
      controlled trial was performed to test the hypothesis that a daily intake of
      Chlorella may improve serum lipid profile through enhancement of serum carotenoid
      concentration in mildly hypercholesterolemic subjects. METHODS: Eligible subjects
      (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double
      blinded trial with a 2-week lead-in period and a 4-week intervention period.
      Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and
      carotenoids were assessed at the beginning and the end of the trial. RESULTS:
      Compared with the control group, the Chlorella group exhibited remarkable changes
      in total cholesterol (Chlorella -1.6%; placebo 0.03%; P = 0.036), triglycerides
      (Chlorella -10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%;
      placebo -1.7%; P < 0.0001), and alpha-carotene (Chlorella 163.6%; placebo 15%; P
      < 0.0001). Improvement of serum lipids was supported by significant reductions of
      very low-density lipoprotein cholesterol (Chlorella -11%; placebo 11.8%; P =
      0.006), apolipoprotein B (Chlorella -1.5%; placebo 1.7%; P = 0.044), non high
      density lipoprotein (Chlorella -2.6%; placebo -0.5%; P = 0.032), and high-density
      lipoprotein/triglycerides (Chlorella 4.0%; placebo -9.5%; P = 0.023), suggesting
      an inhibitory effect of Chlorella on the intestinal absorption of dietary and
      endogenous lipids. Further, the changes of serum lipids appeared to be associated
      with the changes of serum carotenoids. CONCLUSION: Daily consumption of Chlorella
      supplements provided the potential of health benefits reducing serum lipid risk
      factors, mainly triglycerides and total cholesterol, in mildly
      hypercholesterolemic subjects. The effect was related to carotenoid consumption.
      TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform
      KCT0000259.

PMID- 24920271
TI  - Dichotomisation of a continuous outcome and effect on meta-analyses: illustration
      of the distributional approach using the outcome birthweight.
AB  - BACKGROUND: Power and precision are greater in meta-analyses than individual
      study analyses. However, dichotomisation of continuous outcomes in certain
      studies poses a problem as estimates from primary studies can only be pooled if
      they have a common outcome. Meta-analyses may include pooled summaries of either
      or both the continuous and dichotomous forms, and potentially have a different
      combination of studies for each depending on whether the outcome was dichotomised
      in the primary studies or not. This dual-outcome issue can lead to loss of power
      and/or selection bias. In this study we aimed to illustrate how dichotomisation
      of a continuous outcome in primary studies may result in biased estimates of
      pooled risk and odds ratios in meta-analysis using secondary analyses of
      published meta-analyses with the outcome, birthweight, which is commonly analysed
      both as continuous, and dichotomous (low birthweight: birthweight < 2,500 g).
      METHODS: Meta-analyses published in January 2010 - December 2011 were obtained
      using searches in PubMed, Embase, Web of Science, and Cochrane Database of
      Systematic Reviews with the outcome birthweight. We used a distributional method
      to estimate the pooled odds/risk ratio of low birthweight and its standard error
      as a function of the data reported in the primary studies of the included meta
      analyses where accessible. RESULTS: Seventy-six meta-analyses were identified.
      Thirty-seven percent (28/76) of the meta-analyses reported only the dichotomous
      form of the outcome while 26% (20/76) reported only the continuous form. In one
      meta-analysis (1/76), birthweight was analysed as continuous for one intervention
      and as binary for another and 36% (27/76) presented both dichotomous and
      continuous birthweight summaries. In meta-analyses with a continuous outcome,
      primary studies data were accessible in 39/48 and secondary analyses using the
      distributional approach provided consistent inferences for both the continuous
      and distributional estimates in 38/39. CONCLUSION: The distributional method
      applied in primary studies allows both a continuous and dichotomous outcome to be
      estimated providing consistent inferences. The use of this method in primary
      studies may restrict selective outcome bias in meta-analyses.

PMID- 24920272
TI  - Factors Affecting Job Satisfaction of Immigrant Korean Nurses.
AB  - PURPOSE: An increasing number of foreign-born nurses are working in the United
      States. Nurses' job satisfaction is a critical issue for quality patient care.
      The purpose of this study was to examine factors affecting the job satisfaction
      of immigrant Korean nurses. DESIGN: We used a cross-sectional mailed survey
      design. A convenience sample (n = 105) of members of the Greater New York Korean
      Nurses Association currently working or had previously worked in the United
      States completed the questionnaires. We used hierarchical regression to test the
      effects of acculturation and life satisfaction on job satisfaction. RESULTS: Most
      participants were female (n = 98, 93.3%) aged 27 to 70 years (mean = 52.27 years,
      SD = 10.67). In the regression model, life satisfaction, self-esteem, and
      perceived stress predicted job satisfaction (F = 5.127, p < .001) and explained
      44.5% of the variance of job satisfaction. DISCUSSION AND CONCLUSION: U.S. nurses
      need to gain insight into factors influencing job satisfaction in Korean nurses
      to promote retention and quality care.

PMID- 24920273
TI  - Spontaneous running wheel improves cognitive functions of mouse associated with
      miRNA expressional alteration in hippocampus following traumatic brain injury.
AB  - Traumatic brain injury (TBI) is an insult to the brain that results in
      impairments of cognitive and physical functioning. Both of human research and
      animal studies demonstrate that spontaneous exercise can facilitate neuronal
      plasticity and improve cognitive function in normal or TBI rodent models.
      However, the possible mechanisms underlying are still not well known. We
      postulated that spontaneous running wheel (RW) altered microRNA (miRNA)
      expressions in hippocampus of mice following TBI, which might be associated with
      the improvement in cognitive functions. In the present study, acquisition of
      spatial learning and memory retention was assessed by using the Morris water maze
      (MWM) test on days 15 post RW exercise. Then, microarray analyses in miRNA files
      were employed, and the expressional changes of miRNAs in the hippocampus of mice
      were detected. The results showed that spontaneous RW exercise (i) recovered the
      hippocampus-related cognitive deficits induced by TBI, (ii) altered hippocampal
      expressions of miRNAs in both of sham and TBI mice, and (iii) miR-21 or miR-34a
      was associated with the recovery process. The present results indicated that an
      epigenetic mechanism might be involved in voluntary exercise-induced cognitive
      improvement of mice that suffered from TBI. 

PMID- 24920274
TI  - Meiotic long non-coding meiRNA accumulates as a dot at its genetic locus
      facilitated by Mmi1 and plays as a decoy to lure Mmi1.
AB  - Long non-coding RNAs (lncRNAs) play key roles in the formation of nuclear bodies.
      In the fission yeast Schizosaccharomyces pombe, a lncRNA species termed meiRNA
      forms a nuclear dot structure at its own genetic locus, the sme2 locus, with its
      protein-binding partner Mei2. This dot structure, called Mei2 dot, promotes the
      progression of meiosis by suppressing Mmi1, a crucial factor involved in the
      selective elimination of meiosis-specific transcripts. The meiRNA itself is a
      target of Mmi1-mediated elimination and is supposed to function as a decoy to
      lure Mmi1. However, detailed mechanisms underlying the formation of Mei2 dot and
      inactivation of Mmi1 remain ambiguous. Here, we show that the localization of
      meiRNA, at its genetic locus sme2, depends on its association with Mmi1. We also
      demonstrate that one of the multiple Mmi1 foci in mitotic cells localizes to the
      sme2 locus. Furthermore, the overexpression of meiRNA promotes the accumulation
      of Mmi1 to the sme2 locus even in the absence of Mei2 and reduces the activity of
      Mmi1. These findings indicate that the retention of meiRNA at its genetic locus
      is facilitated by Mmi1, which then attracts scattered Mmi1 to inhibit its
      function. 

PMID- 24920275
TI  - Effect of erythropoietin on primed leucocyte expression profile.
AB  - Resistance to erythropoietin (EPO) affects a significant number of anaemic
      patients with end-stage renal disease. Previous reports suggest that inflammation
      is one of the major independent predictors of EPO resistance, and the effects of
      EPO treatment on inflammatory mediators are not well established. The aim of this
      study was to investigate EPO-induced modification to gene expression in primary
      cultured leucocytes. Microarray experiments were performed on primed ex vivo
      peripheral blood mononuclear cells (PBMCs) and treated with human EPO-alpha. Data
      suggested that EPO-alpha modulated genes involved in cell movement and
      interaction in primed PBMCs. Of note, EPO-alpha exerts anti-inflammatory effects
      inhibiting the expression of pro-inflammatory cytokine IL-8 and its receptor
      CXCR2; by contrast, EPO-alpha increases expression of genes relating to promotion
      of inflammation encoding for IL-1beta and CCL8, and induces de novo synthesis of
      IL-1alpha, CXCL1 and CXCL5 in primed cells. The reduction in MAPK p38-alpha
      activity is involved in modulating both IL-1beta and IL-8 expression. Unlike the
      induction of MAPK, Erk1/2 activity leads to upregulation of IL-1beta, but does
      not affect IL-8 expression and release. Furthermore, EPO-alpha treatment of
      primed cells induces the activation of caspase-1 upstream higher secretion of IL
      1beta, and this process is not dependent on caspase-8 activation. In conclusion,
      our findings highlight new potential molecules involved in EPO resistance and
      confirm the anti-inflammatory role for EPO, but also suggest a plausible in vivo
      scenario in which the positive correlation found between EPO resistance and
      elevated levels of some pro-inflammatory mediators is due to treatment with EPO
      itself. 

PMID- 24920276
TI  - Differential regulation of aggressive features in melanoma cells by members of
      the miR-17-92 complex.
AB  - The various roles of microRNAs (miRNAs) in controlling the phenotype of cancer
      cells are the focus of contemporary research efforts. We have recently shown that
      miR-17 directly targets the ADAR1 gene and thereby enhances melanoma cell
      aggressiveness. miR-17 and miR-20a belong to the miR-17/92 complex, and their
      mature forms are identical except for two non-seed nucleotides. Nevertheless,
      here we show that these two miRNAs carry markedly different effects on melanoma
      cells. A strong positive correlation was observed between the expression of miR
      17 and miR-20a among various melanoma cultures. Luciferase assays showed that miR
      17 but not miR-20a directly targets the 3' untranslated region of the ADAR1 gene.
      Ectopic expression of these miRNAs in melanoma cells differentially alters the
      expression of five exemplar TargetScan-predicted target genes: ADAR1, ITGB8,
      TGFBR2, MMP2 and VEGF-A. Whole-genome expression microarrays confirm a markedly
      differential effect on the transcriptome. Functionally, over-expression of miR
      20a but not of miR-17 in melanoma cells inhibits net proliferation in vitro. The
      differential functional effect was observed following ectopic expression of the
      mature miRNA or of the pre-miRNA sequences. This suggests that the two non-seed
      nucleotides dictate target sequence recognition and overall functional relevance.
      These miRNAs are clearly not redundant in melanoma cell biology. 

PMID- 24920277
TI  - Dapagliflozin added to glimepiride in patients with type 2 diabetes mellitus
      sustains glycemic control and weight loss over 48 weeks: a randomized, double
      blind, parallel-group, placebo-controlled trial.
AB  - INTRODUCTION: Maintenance of drug efficacy and safety over the long term is
      important to investigate for progressive conditions like type 2 diabetes mellitus
      (T2DM). This study aimed to evaluate whether efficacy of dapagliflozin added to
      glimepiride observed at 24 weeks was maintained at 48 weeks, and to provide
      further safety and tolerability data in patients with T2DM. METHODS: This 24-week
      randomized, double-blind, parallel-group, placebo-controlled trial with a 24-week
      double-blind extension period enrolled adults whose T2DM was inadequately
      controlled [glycated hemoglobin (HbA1c) 7.0-10.0%] on sulfonylurea monotherapy.
      Patients were randomized to placebo (n = 146) or dapagliflozin 2.5 mg (n = 154),
      5 mg (n = 145), or 10 mg (n = 151) per day added to open-label glimepiride 4
      mg/day. RESULTS: In total, 519 patients (87.1%) completed the study. At 48 weeks,
      HbA1c adjusted mean changes from baseline for the placebo versus dapagliflozin
      2.5/5/10-mg groups were -0.04% versus -0.41%, -0.56% and -0.73%, respectively.
      There were no meaningful differences in HbA1c changes from baseline from 24 to 48
      weeks, indicating that glycemic efficacy was maintained. Improvements in fasting
      plasma glucose and post-challenge plasma glucose were also observed with
      dapagliflozin over 48 weeks. Dapagliflozin 2.5/5/10 mg produced sustained
      reductions in weight (-1.36/-1.54/-2.41 kg) versus placebo (-0.77 kg). Adjusted
      mean reductions from baseline in systolic blood pressure were also greater than
      placebo for all dapagliflozin doses. In the placebo versus dapagliflozin groups,
      serious adverse events were 8.9% versus 8.6-11.0%, hypoglycemic events were 6.8%
      versus 9.7-11.3%, and events suggestive of genital infection were 1.4% versus 5.2
      8.6%. CONCLUSION: Dapagliflozin added to glimepiride improved glycemic control
      and body weight, with short-term findings maintained during the study's extension
      period. Therapy was generally well tolerated over 48 weeks; hypoglycemic events
      and events suggestive of genital infection were reported more often in patients
      receiving dapagliflozin.

PMID- 24920278
TI  - Design and implementation of an online systemic human anatomy course with
      laboratory.
AB  - Systemic Human Anatomy is a full credit, upper year undergraduate course with a
      (prosection) laboratory component at Western University Canada. To meet
      enrollment demands beyond the physical space of the laboratory facility, a fully
      online section was developed to run concurrently with the traditional face to
      face (F2F) course. Lectures given to F2F students are simultaneously broadcasted
      to online students using collaborative software (Blackboard Collaborate). The
      same collaborative software is used by a teaching assistant to deliver laboratory
      demonstrations in which three-dimensional (3D) virtual anatomical models are
      manipulated. Ten commercial software programs were reviewed to determine their
      suitability for demonstrating the virtual models, resulting in the selection of
      Netter's 3D Interactive Anatomy. Supplementary online materials for the central
      nervous system were developed by creating 360 degrees  images of plastinated
      prosected brain specimens and a website through which they could be accessed.
      This is the first description of a fully online undergraduate anatomy course with
      a live, interactive laboratory component. Preliminary data comparing the online
      and F2F student grades suggest that previous student academic performance, and
      not course delivery format, predicts performance in anatomy. Future qualitative
      studies will reveal student perceptions about their learning experiences in both
      of the course delivery formats.

PMID- 24920279
TI  - A genomic perspective on the important genetic mechanisms of upland adaptation of
      rice.
AB  - BACKGROUND: Cultivated rice consists of two important ecotypes, upland and
      irrigated, that have respectively adapted to either dry land or irrigated
      cultivation. Upland rice, widely adopted in rainfed upland areas in virtue of its
      little water requirement, contains abundant untapped genetic resources, such as
      genes for drought adaptation. With water shortage exacerbated and population
      expanding, the need for breeding crop varieties with drought adaptation becomes
      more and more urgent. However, a previous oversight in upland rice research
      reveals little information regarding its genetic mechanisms for upland adaption,
      greatly hindering progress in harnessing its genetic resources for breeding and
      cultivation. RESULTS: In this study, we selected 84 upland and 82 irrigated
      accessions from all over the world, phenotyped them under both irrigated and dry
      land environments, and investigated the phylogenetic relations and population
      structure of the upland ecotype using whole genome variation data. Further
      comparative analysis yields a list of differentiated genes that may account for
      the phenotypic and physiological differences between upland and irrigated rice.
      CONCLUSIONS: This study represents the first genomic investigation in a large
      sample of upland rice, providing valuable gene list for understanding upland rice
      adaptation, especially drought-related adaptation, and its subsequent utilization
      in modern agriculture.

PMID- 24920280
TI  - Isolated hyperthyrotropinemia in childhood obesity and its relation with
      metabolic parameters.
AB  - PURPOSE: The aim of the presented study was to evaluate the prevalence of
      isolated hyperthyrotropinemia (IH) in obese children and the relation between
      anthropometric and metabolic parameters. METHODS: Hospital records of the
      children, who presented to the Pediatric Endocrinology outpatient clinic of our
      institution with obesity, and age and gender-matched healthy children, who had
      undergone thyroid function test for any reason were retrospectively reviewed.
      RESULTS: The prevalence of IH was significantly higher in the obese group than in
      the controls (9.2 and 3.8 %, respectively). Body mass index-standard deviation
      score (BMI-SDS), thyroid-stimulating hormone (TSH), lipid parameters were
      significantly different in the obese group than in the control group. A positive
      correlation between TSH and BMI-SDS and negative correlation between TSH and free
      T4 (fT4) levels were found in obese subjects. Stepwise multiple linear regression
      analysis confirmed that BMI-SDS, fT4 and triglyceride levels were the strongest
      independent variables correlated with TSH level in obese subjects (r (2) = 0.046,
      p = 0.001). CONCLUSIONS: IH prevalence is higher in obese children as compared to
      healthy children and the increase in TSH level correlates negatively with serum
      fT4 and positively with BMI-SDS and triglyceride levels in obese children.

PMID- 24920281
TI  - Plasma nesfatin-1 levels are increased in patients with polycystic ovary
      syndrome.
AB  - BACKGROUND: Nesfatin-1 is a recently discovered neuropeptide derived from its
      precursor nucleobindin-2 (NUCB2) and has been implicated in the regulation of
      feeding and energy metabolism. It is located in the brain and also produced at
      the periphery and present in the plasma. However, its pathophysiological role in
      humans remains unknown. Polycystic ovary syndrome (PCOS) is commonly presented
      with obesity, insulin resistance, hyperandrogenemia and hirsutism. AIM: To
      characterize serum nesfatin-1 levels in PCOS women and determine association of
      nesfatin-1 with metabolic parameters. MATERIALS AND METHODS: It is a cross
      sectional study of 55 PCOS and 28 healthy women matched in age, in a university
      hospital setting. Anthropometric, hormonal, metabolic parameters and nesfatin-1
      blood levels were determined. RESULTS: Nesfatin-1 levels were significantly
      higher in PCOS group compared with the controls 371.43 +/- 2.50 versus 275.55 +/-
      1.74 pg/mL. Multivariate logistic regression analysis that contains: nesfatin-1,
      body mass index and homeostasis model assessment index revealed significant
      correlation of nesfatin-1 with the existence of PCOS (p < 0.05). CONCLUSIONS:
      Higher nesfatin-1 levels in PCOS women compared to control group may suggest a
      possibility that nesfatin-1 may play some role in the PCOS.

PMID- 24920282
TI  - Postural balance in pregnancies complicated by hyperemesis gravidarum.
AB  - OBJECTIVE: To assess postural balance in females with pregnancies complicated by
      hyperemesis gravidarum (HG). METHODS: In this observational study, postural
      balance during the first trimester was measured using the Biodex Balance System
      (BBS) in 41 pregnant females (20 females with pregnancies complicated by HG and
      21 healthy controls). The overall stability index (OA), anterior-posterior
      stability index (APSI), medial-lateral stability index (MLSI) and fall risk test
      (FRT) scores were obtained from the mean scores of three trials on the BSS. The
      four measurements obtained from the BBS (OA, APSI, MLSI and FRT) were compared
      between healthy pregnant females and those with pregnancies complicated by HG (HG
      group). RESULTS: The mean OA and APSI scores were significantly higher in the HG
      group compared to healthy pregnant controls (p < 0.01). There was no significant
      difference in the MLSI between the two groups (p > 0.05). The FRT scores of HG
      patients were higher than healthy pregnant females (p = 0.001). CONCLUSIONS:
      Pregnant females with HG have poor postural stability/balance and high fall risk
      test scores. HG causes decreased postural equilibrium in the first trimester of
      pregnancy.

PMID- 24920283
TI  - Oxytocin, its antagonist Atosiban, and preterm labor: a role for placental nitric
      oxide.
AB  - OBJECTIVE: The aim of the present study was to understand the role played by
      Atosiban, an oxytocin receptor antagonist, on trophoblastic human cells, and the
      molecular bases of its efficacy and safety in the treatment of preterm labor. NO,
      peroxinitrite production and NOS expression have been evaluated on placenta
      obtained from term and preterm labors. PATIENTS AND METHODS: We studied
      trophoblast cells isolated from selected placental tissue from 20 controls and 20
      preterm patients after cesarean sections. Each sample was studied at basal state
      and after 2 hours incubation with oxytocin and Atosiban. RESULTS: Significant
      variations of NO levels, peroxynitrite production and iNOS and eNOS expression
      both in the preterm, term samples and in each of the considered groups were
      observed. In the control group Atosiban re-established NO levels that were
      reduced after incubation with oxytocin, while in preterm samples NO levels were
      not only re-established but, after incubation with Atosiban, significantly
      increased compared to basal levels. CONCLUSIONS: This confirms the beneficial
      role of Atosiban in prolonging the pregnancy of spontaneous labor at very early
      gestational periods. In conclusion, Atosiban might be an effective drug to
      prevent preterm labor, in the therapeutic approach to this pathology.

PMID- 24920284
TI  - The early bird catches the worm - predicting the onset of gestational diabetes in
      the first trimester.

PMID- 24920285
TI  - Processing of emotion words by patients with autism spectrum disorders: evidence
      from reaction times and EEG.
AB  - This study investigated processing of emotion words in autism spectrum disorders
      (ASD) using reaction times and event-related potentials (ERP). Adults with (n =
      21) and without (n = 20) ASD performed a lexical decision task on emotion and
      neutral words while their brain activity was recorded. Both groups showed faster
      responses to emotion words compared to neutral, suggesting intact early
      processing of emotion in ASD. In the ERPs, the control group showed a typical
      late positive component (LPC) at 400-600 ms for emotion words compared to
      neutral, while the ASD group showed no LPC. The between-group difference in LPC
      amplitude was significant, suggesting that emotion words were processed
      differently by individuals with ASD, although their behavioral performance was
      similar to that of typical individuals.

PMID- 24920288
TI  - L-Dihydroxyphenylalanine induces melanin production by members of the genus
      Trichosporon.
AB  - Melanization of members of the genus Trichosporon is poorly described. In this
      study, six strains, including two clinical isolates, from four different species
      (Trichosporon asahii, T. asteroides, T. inkin, and T. mucoides) were grown in
      culture media with or without L-dihydroxyphenylalanine (L-DOPA). Each strain
      produced a brownish pigment compatible with melanin when cultured in presence of
      L-DOPA, suggesting that these species are able to produce eumelanin. L-tyrosine
      was not able to elicit any type of pigment production on cultures. As eumelanin
      is produced by several fungi during parasitism, this pigment may contribute to
      Trichosporon virulence.

PMID- 24920287
TI  - Pregnant women with posttraumatic stress disorder and risk of preterm birth.
AB  - IMPORTANCE: Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant
      women. Stressful conditions, including PTSD, are inconsistently linked to preterm
      birth. Psychotropic treatment has been frequently associated with preterm birth.
      Identifying whether the psychiatric illness or its treatment is independently
      associated with preterm birth may help clinicians and patients when making
      management decisions. OBJECTIVE: To determine whether a likely diagnosis of PTSD
      or antidepressant and benzodiazepine treatment during pregnancy is associated
      with risk of preterm birth. We hypothesized that pregnant women who likely had
      PTSD and women receiving antidepressant or anxiolytic treatment would be more
      likely to experience preterm birth. DESIGN, SETTING, AND PARTICIPANTS:
      Longitudinal, prospective cohort study of 2654 women who were recruited before 17
      completed weeks of pregnancy from 137 obstetrical practices in Connecticut and
      Western Massachusetts. EXPOSURES: Posttraumatic stress disorder, major depressive
      episode, and use of antidepressant and benzodiazepine medications. MAIN OUTCOMES
      AND MEASURES: Preterm birth, operationalized as delivery prior to 37 completed
      weeks of pregnancy. Likely psychiatric diagnoses were generated through
      administration of the Composite International Diagnostic Interview and the
      Modified PTSD Symptom Scale. Data on medication use were gathered at each
      participant interview. RESULTS: Recursive partitioning analysis showed elevated
      rates of preterm birth among women with PTSD. A further split of the PTSD node
      showed high rates for women who met criteria for a major depressive episode,
      which suggests an interaction between these 2 exposures. Logistic regression
      analysis confirmed risk for women who likely had both conditions (odds ratio
      [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD
      Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%.
      The odds of preterm birth are high for women who used a serotonin reuptake
      inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine
      medication (OR, 1.99 [95% CI, 0.98-4.03]). CONCLUSIONS AND RELEVANCE: Women with
      likely diagnoses of both PTSD and a major depressive episode are at a 4-fold
      increased risk of preterm birth; this risk is greater than, and independent of,
      antidepressant and benzodiazepine use and is not simply a function of mood or
      anxiety symptoms.

PMID- 24920289
TI  - GEP-NETS update: a review on surgery of gastro-entero-pancreatic neuroendocrine
      tumors.
AB  - The incidence of neuroendocrine tumors (NETs) has increased in the last decades.
      Surgical treatment encompasses a panel of approaches ranging from conservative
      procedures to extended surgical resection. Tumor size and localization usually
      represent the main drivers in the choice of the most appropriate surgical
      resection. In the presence of small (<2 cm) and asymptomatic nonfunctioning NETs,
      a conservative treatment is usually recommended. For localized NETs measuring
      above 2 cm, surgical resection represents the cornerstone in the management of
      these tumors. As they are relatively biologically indolent, an extended resection
      is often justified also in the presence of advanced NETs. Surgical options for
      NET liver metastases range from limited resection up to liver transplantation.
      Surgical choices for metastatic NETs need to consider the extent of disease, the
      grade of tumor, and the presence of extra-abdominal disease. Any surgical
      procedures should always be balanced with the benefit of survival or relieving
      symptoms and patients' comorbidities. 

PMID- 24920290
TI  - Endocrinology and Adolescence: aerobic exercise reduces insulin resistance
      markers in obese youth: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The purpose of this meta-analysis was to examine the evidence for the
      effectiveness of aerobic exercise interventions on reducing insulin resistance
      markers in obese children and/or adolescents. A secondary outcome was change in
      percentage of body fat. METHODS: A computerized search was made from seven
      databases: CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ERIC,
      MEDLINE, PsycINFO, and Science Citation Index. The analysis was restricted to
      randomized controlled trials that examined the effect of aerobic exercise on
      insulin resistance markers in obese youth. Two independent reviewers screened
      studies and extracted data. Effect sizes (ES) and 95% confidence interval (CI)
      were calculated, and the heterogeneity of the studies was estimated using
      Cochran's Q-statistic. RESULTS: Nine studies were selected for meta-analysis as
      they fulfilled the inclusion criteria (n=367). Aerobic exercise interventions
      resulted in decreases in fasting glucose (ES=-0.39; low heterogeneity) and
      insulin (ES=-0.40; low heterogeneity) and in percentage of body fat (ES=-0.35;
      low heterogeneity). These improvements were specifically accentuated in
      adolescents (only in fasting insulin), or through programs lasting more than 12
      weeks, three sessions per week, and over 60 min of aerobic exercise per session.
      CONCLUSIONS: This meta-analysis provides insights into the effectiveness of
      aerobic exercise interventions on insulin resistance markers in the obese youth
      population.

PMID- 24920292
TI  - Plasma irisin levels progressively increase in response to increasing exercise
      workloads in young, healthy, active subjects.
AB  - BACKGROUND: Irisin, a recently discovered myokine, has been shown to induce
      browning of white adipose tissue, enhancing energy expenditure and mediating some
      of the beneficial effects of exercise. We aimed to estimate the time frame of
      changes in irisin levels after acute exercise and the effect of different
      exercise workloads and intensities on circulating irisin levels immediately post
      exercise. METHODS: In a pilot study, four healthy subjects (22.5+/-1.7 years)
      underwent maximal workload exercise (maximal oxygen consumption, VO2 max) and
      blood was drawn at prespecified intervals to define the time frame of pre- and
      post-exercise irisin changes over a 24-h period. In the main study, 35 healthy,
      non-smoking (23.0+/-3.3 years) men and women (n=20/15) underwent three exercise
      protocols >=48-h apart, in random order: i) maximal workload (VO2 max); ii)
      relative workload (70% of VO2 max/10 min); and iii) absolute workload (75 W/10
      min). Blood was drawn immediately pre-exercise and 3 min post-exercise. RESULTS:
      In the pilot study, irisin levels increased by 35% 3 min post-exercise, then
      dropped and remained relatively constant. In the main study, irisin levels post
      exercise were significantly higher than those of pre-exercise after all workloads
      (all, P<0.001). Post-to-pre-exercise differences in irisin levels were
      significantly different between workloads (P=0.001), with the greatest increase
      by 34% following maximal workload (P=0.004 vs relative and absolute).
      CONCLUSIONS: Circulating irisin levels were acutely elevated in response to
      exercise, with a greater increase after maximal workload. These findings suggest
      that irisin release could be a function of muscle energy demand. Future studies
      need to determine the underlying mechanisms of irisin release and explore
      irisin's therapeutic potential.

PMID- 24920291
TI  - Association between the p27 rs2066827 variant and tumor multiplicity in patients
      harboring MEN1 germline mutations.
AB  - OBJECTIVE: To date, no evidence of robust genotype-phenotype correlation or
      disease modifiers for multiple endocrine neoplasia type 1 (MEN1) syndrome has
      been described, leaving the highly variable clinical presentation of patients
      unaccounted for. DESIGN: As the CDKN1B (p27) gene causes MEN4 syndrome and it is
      transcriptionally regulated by the product of the MEN1 gene (menin), we sought to
      analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort
      consisted of 100 patients carrying germline MEN1 gene mutations and 855
      population-matched control individuals. METHODS: Genotyping of the coding p27
      c.326T>G (V109G) variant was performed by sequencing and restriction site
      digestion, and the genotypes were associated with clinical parameters by
      calculating odds ratios (ORs) and their 95% CIs using logistic regression.
      RESULTS: There were significant differences in p27 V109G allele frequencies
      between controls and MEN1-mutated patients (OR=2.55, P=0.019, CI=1.013-5.76).
      Among patients who are >=30 years old carrying truncating MEN1 mutations, the T
      allele was strongly associated with susceptibility to tumors in multiple glands
      (three to four glands affected vs one to two glands affected; OR=18.33; P=0.002,
      CI=2.88-16.41). This finding remained significant after the Bonferroni's multiple
      testing correction, indicating a robust association. No correlations were
      observed with the development of MEN1-related tumors such as hyperparathyroidism,
      pituitary adenomas, and enteropancreatic and adrenocortical tumors. CONCLUSIONS:
      Our study suggests that the p27 tumor suppressor gene acts as a disease modifier
      for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in
      independent patient cohorts, this finding could facilitate the management of this
      clinically complex disease.

PMID- 24920293
TI  - First-trimester exposure to bupropion and risk of cardiac malformations.
AB  - PURPOSE: Bupropion is a drug uniquely used both to treat depression and as an aid
      to smoking cessation. We investigated previously reported associations between
      first-trimester exposure to bupropion and cardiac defects. METHODS: Using data
      gathered since 2003 by the Slone Epidemiology Center's Case-control Birth Defects
      Study, we classified subjects with cardiac defects into subgroups. Exposure
      categories included first-trimester bupropion alone or in combination with other
      antidepressants, first-trimester antidepressants other than bupropion, and no
      exposure to any antidepressant at any time from 2 months prior to pregnancy
      through delivery. We calculated odds ratios and 95% confidence intervals,
      controlling for confounding using logistic regression. RESULTS: There were 8611
      non-malformed infants and 7913 infants with cardiac defects. Eight cardiac
      subgroups had sufficient subjects (two or more exposed cases) for analysis. The
      adjusted odds ratio (aOR) for first-trimester bupropion use in relation to
      ventricular septal defect (VSD) was slightly elevated (1.6, 95% confidence
      interval 1.0-2.8); for exposure to bupropion alone, the aOR was 2.5 (95%
      confidence interval 1.3-5.0). Risks were not materially elevated for bupropion in
      relation to the other seven cardiac subgroups. CONCLUSIONS: We did not confirm
      previously reported associations for left-sided defects overall but had too few
      exposed cases to evaluate specific defects in this category. We did observe an
      elevated risk of VSD following first-trimester bupropion use, particularly when
      used without other antidepressants. This pattern for bupropion alone was observed
      in all our risk comparisons and was not explained by higher doses or gestational
      timing.

PMID- 24920295
TI  - Bioterrorism: myth or reality?

PMID- 24920294
TI  - Combination of hemoglobin and left ventricular ejection fraction as a new
      predictor of contrast induced nephropathy in patients with non-ST elevation
      myocardial infarction.
AB  - BACKGROUND: Hemoglobin concentration (Hb) and left ventricular ejection fraction
      (EF) are known predictors of contrast induced nephropathy (CIN). We hypothesized
      that combination of Hb concentration and left ventricular EF is superior to
      either variable alone in predicting contrast induced nephropathy in patients with
      acute coronary syndrome (ACS). MATERIAL AND METHODS: Consecutive patients with
      ACS were prospectively enrolled. Patients considered for invasive strategy were
      included. Baseline creatinine levels were detected on admission and 24, 48 and 72
      hours after coronary intervention. 25% or 0,5 umol/L increase in creatinine level
      was considered as CIN. RESULTS: 268 patients with ACS (mean age 58+/-11 years,
      77% male) were enrolled. Contrast induced nephropathy was observed in 26 (9.7%)
      of patients. Baseline creatinine concentration, left ventricular EF, and
      Hemoglobin was significantly different between two groups. Contrast volume to
      estimated glomerular filtration rate ratio (OR: 1.310, 95% CI: 1.077-1.593,
      p=0.007) and the combination of Hb and left ventricular EF (OR: 0.996, 95% CI:
      0.994-0.998, p=0.001) were found to be independent predictors for CIN. Hb * LVEF
      <=690 had 85% sensitivity and 57% specificity to predict CIN (area under curve:
      0.724, 95% CI: 0.625-0.824, p<0.001). In addition, Hb * LVEF <=690 had a negative
      predictive value of 97% in our analysis CONCLUSIONS: The combination of Hb and
      left ventricular EF is better than either variable alone at predicting CIN in
      patients with ACS that undergone percutaneous coronary intervention. The
      prediction was independent of baseline renal function and volume of contrast
      agent.

PMID- 24920296
TI  - RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling
      after myocardial infarction.
AB  - AIMS: Programmed necrosis (necroptosis) represents a newly identified mechanism
      of cell death combining features of both apoptosis and necrosis. Like apoptosis,
      necroptosis is tightly regulated by distinct signalling pathways. A key
      regulatory role in programmed necrosis has been attributed to interactions of the
      receptor-interacting protein kinases, RIP1 and RIP3. However, the specific
      functional role of RIP3-dependent signalling and necroptosis in the heart is
      unknown. The aims of this study were thus to assess the significance of
      necroptosis and RIP3 in the context of myocardial ischaemia. METHODS AND RESULTS:
      Immunoblots revealed strong expression of RIP3 in murine hearts, indicating
      potential functional significance of this protein in the myocardium. Consistent
      with a role in promoting necroptosis, adenoviral overexpression of RIP3 in
      neonatal rat cardiomyocytes and stimulation with TNF-alpha induced the formation
      of a complex of RIP1 and RIP3. Moreover, RIP3 overexpression was sufficient to
      induce necroptosis of cardiomyocytes. In vivo, cardiac expression of RIP3 was up
      regulated upon myocardial infarction (MI). Conversely, mice deficient for RIP3
      (RIP3(-/-)) showed a significantly better ejection fraction (45 +/- 3.6 vs. 32 +/
      4.4%, P < 0.05) and less hypertrophy in magnetic resonance imaging studies 30
      days after experimental infarction due to left anterior descending coronary
      artery ligation. This was accompanied by a diminished inflammatory response of
      infarcted hearts and decreased generation of reactive oxygen species. CONCLUSION:
      Here, we show that RIP3-dependent necroptosis modulates post-ischaemic adverse
      remodelling in a mouse model of MI. This novel signalling pathway may thus be an
      attractive target for future therapies that aim to limit the adverse consequences
      of myocardial ischaemia.

PMID- 24920297
TI  - Right portal vein embolization with absolute ethanol in major hepatic resection
      for hepatobiliary malignancy.
AB  - BACKGROUND: This study aimed to evaluate the safety and efficacy of preoperative
      right portal vein embolization (PVE) with absolute ethanol in patients with
      hepatobiliary malignancies. METHODS: PVE was performed via a percutaneous
      transhepatic ipsilateral approach, and the right portal branch was embolized with
      absolute ethanol. Technical success and complications following PVE, and changes
      in liver enzyme levels were evaluated. Changes in future liver remnant (FLR) and
      FLR/total functional liver volume ratio were calculated. Complications following
      hepatic resection were assessed. RESULTS: A total of 83 patients with
      hepatobiliary malignancies (53 men, 30 women; mean age 68 years) underwent right
      PVE. Tumour types were hilar cholangiocarcinoma (37), liver metastases (14),
      gallbladder cancer (13), intrahepatic cholangiocellular carcinoma (10) and
      hepatocellular carcinoma (HCC) (9). PVE was performed successfully in all
      patients. Four patients (5 per cent) developed complications following PVE (liver
      abscess 2, left portal vein thrombosis 1, pseudoaneurysm 1), but this did not
      preclude hepatic resection. Liver enzyme levels rose transiently after PVE. The
      mean FLR and FLR/total functional liver volume increased after PVE (from 366 to
      513 cm(3) and from 31 to 43 per cent respectively; both P < 0.001). Changes in
      the FLR and FLR/total functional liver volume ratio were comparable between
      patients with HCC and those with other malignancies (42 and 44 per cent, and 12
      and 12 per cent, respectively). Sixty-nine of 83 patients underwent hepatic
      resection at a median of 25 days after PVE, with no postoperative mortality.
      CONCLUSION: Preoperative right PVE with absolute ethanol is safe and effective
      for induction of selective hepatic hypertrophy in patients with hepatobiliary
      malignancy.

PMID- 24920298
TI  - Meta-analysis of handsewn versus stapled reversal of loop ileostomy.
AB  - BACKGROUND: The morbidity associated with closure of loop ileostomy (LI) may be
      attributed to the various surgical techniques employed for the closure. The
      purpose of this review was to review the hand-sutured (HS) versus the stapled
      anastomosis (SA) techniques, used in the reversal of LI. METHODS: The MEDLINE,
      PubMed, CINHAL, Cochrane library and Web of Knowledge databases were searched for
      randomized controlled trials (RCTs) and case-control trials (CCTs), evaluating HS
      and SA in reversal of LI. Data extraction with risk of bias assessment was
      followed by subgroup and pooled data meta-analysis where applicable per outcome.
      RESULTS: Four RCTs (HS: 321, SA: 328) and 10 CCTs (HS: 2808, SA: 1044) were
      identified, with a total of 4508 patients. Regardless of subgroup analysis, no
      difference was seen between the two techniques with regard to anastomotic leaks
      (P = 0.24, odds ratio (OR): 1.37, 95% confidence interval (CI): 0.81-2.29) or re
      operation. The stapled group showed a significantly lower rate of conservatively
      managed small bowel obstruction (SBO)/ ileus at 30 days (P < 0.001, OR: 2.27, 95%
      CI: 1.59-2.96) (P < 0.001) and SBO during combined short- and long-term follow-up
      (P < 0.001). The SA also showed significant shorter operative time (P = 0.02; WMD
      11.52 min), time to first bowel opening (P < 0.001; WMD 0.52 days) and length of
      hospital stay (P = 0.03; WMD 0.70 days). CONCLUSION: The stapled technique offers
      an advantage in terms of lower post-operative subacute SBO rates, a faster
      operative technique and shorter hospitalization times. These perceived benefits
      make it potentially superior to HS for the reversal of LI.

PMID- 24920299
TI  - Identification of cardiac repercussions after intense and prolonged concentric
      isokinetic exercise in young sedentary people.
AB  - INTRODUCTION: Cardiopathies are the world's leading cause of mortality and
      morbidity. Although rare, cardiovascular accidents can occur during intense and
      infrequent sporting activity, particularly among those who are unaware of their
      heart condition. The development of cardiospecific biochemical markers has led to
      a reconsideration of the role of biology in the diagnosis of cardiovascular
      illnesses. The aim of this study therefore was, through the use of cardiac
      biomarker assays, to highlight the impact of sustained physical effort in the
      form of intense and prolonged concentric isokinetic exercise and to research
      potential cardiovascular risks. MATERIALS AND METHODS: Eighteen subjects
      participated in a maximal concentric isokinetic exercise involving 30 knee
      flexion-extensions for each leg. Five blood tests were taken to study the
      kinetics of the cardiac biomarkers. Haemodynamic parameters were measured
      continuously using a Portapres, and respiratory parameters were measured using a
      Sensormedics Vmax 29C. RESULTS: The results showed significant increases in the
      creatine kinase, myoglobin, homocysteine and haemoglobin cardiac markers.
      Evolutionary trends were also observed for the following biomarkers: NT-proBNP,
      myeloperoxydase and C-reactive protein. All the physiological parameters measured
      presented statistically significant changes. CONCLUSION: Isokinetic effort leads
      to the release of cardiac markers in the blood, but these do not exceed the
      reference values in healthy subjects. Maximal concentric isokinetic exercise does
      not, therefore, lead to an increased risk of cardiovascular pathologies.

PMID- 24920300
TI  - Silicate deposition during decomposition of cyanobacteria may promote export of
      picophytoplankton to the deep ocean.
AB  - Marine particles transport organic matter through the water column to the
      sediment where the organic matter can be buried. This pathway is one of the few
      natural removal mechanisms of CO2 from the atmosphere over geological time.
      Picophytoplankton, major primary producers in the ocean, have until recently been
      thought unimportant regarding particle transport. Here we provide evidence that
      silicate is deposited on extracellular polymeric substance (EPS) associated with
      decomposing picophytoplankton. We also find that Si is enriched in a previously
      unexplored group of marine particles (called micro-blebs) from the deep-water
      column. The surprising similarity in morphology and composition between EPS-Si
      and micro-blebs suggests that EPS-Si may be a precursor of micro-blebs observed
      in the deep ocean. This previously unexplored source of silicon may be important
      to silicon cycling and may further enhance export of picophytoplankton to the
      deep ocean. 

PMID- 24920301
TI  - A microfluidic device for evaluating the dynamics of the metabolism-dependent
      antioxidant activity of nutrients.
AB  - Various food components are known for their health-promoting effects. However,
      their biochemical effects are generally evaluated in vitro, and their actual in
      vivo effect can vary significantly, depending on their metabolic profiles. To
      evaluate the effect of the liver metabolism on the antioxidant activity, we have
      developed a two-compartment microfluidic system that integrates the dynamics of
      liver metabolism and the subsequent antioxidant activity of food components. In
      the first compartment of the device, human liver enzyme fractions were
      immobilized inside a poly(ethylene glycol) diacrylate (PEGDA) hydrogel to mimic
      the liver metabolism. The radical scavenging activity was evaluated by the change
      of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance in the second compartment.
      Reaction engineering and fluid mechanics principles were used to develop a
      simplified analytical model and a more complex finite element model, which were
      used to design the chip and determine the optimal flow conditions. For real-time
      measurements of the reaction on a chip, we developed a custom-made
      photospectrometer system with an LED light source. The developed microfluidic
      system showed a linear and dose-dependent antioxidant activity in response to
      increasing concentration of flavonoid. We also compared the antioxidant activity
      of flavonoid after various liver metabolic reactions. This microfluidic system
      can serve as a novel in vitro platform for predicting the antioxidant activity of
      various food components in a more physiologically realistic manner, as well as
      for studying the mechanism of action of such food components. 

PMID- 24920302
TI  - Neural basis of the stress response in a pufferfish, Takifugu obscurus.
AB  - When faced with danger, pufferfish react with both a fast-start escape response
      and inflation behavior. The neural basis of these stress responses in the
      pufferfish has not been described. The present study reveals that during
      inflation behavior, the buccal cavity expands and compresses as a pump to control
      the direction of water flow and draws water in and out. The inflation involves a
      series of major anatomical modifications of the head. The greatly enlarged first
      branchiostegal ray and its associated hyohyoideus abductor muscle are the key
      mechanisms responsible for this behavior. The nerve branch innervating the
      hyohyoideus abductor muscle is highly developed, and its central origin at the
      motor nucleus of the VIIth cranial nerve was revealed by tract-tracing using the
      carbocyanine dye DiI. The central connections from its origin were found to be
      several motor nuclei in the medulla and the spinal cord, the nuclei of cranial
      nerve III and IV in the mesencephalon, and the pretectalis superficialis and
      periventricular preoptic nuclei in the diencephalon. Both the sympathetic cells
      and the parvocellular part of the periventricular preoptic nucleus might play a
      neuro-endocrine role in the rapid movement of the buccal cavity during puffing
      behavior in this species of pufferfish. The central circuit revealed by this
      study is hypothesized to mediate the C-start escape behavior and puffing
      behavior. 

PMID- 24920303
TI  - Controlling the motion of DNA in a nanochannel with transversal alternating
      electric voltages.
AB  - A nanofluidic channel, with a pair of perpendicularly aligned nanoelectrodes, is
      proposed to electrically control the motion of DNA molecules. Using all-atom
      molecular dynamics simulations, we studied electrostatic responses of a charged
      DNA molecule in the nanochannel and investigated optimized operating conditions
      for controlling the DNA molecule. When the transversal electric field was
      periodically turned on and off, the DNA molecule was correspondingly immobilized
      on and released from the channel surface. Under simultaneously applied
      longitudinal biasing and transversal trapping electric fields, the DNA molecule
      moved forward in a 'ratchet'-like fashion. It is expected that achieving the
      controlled motion of DNA in the channel can advance studies and applications of a
      nanochannel-based sensor for analyzing DNA (e.g., DNA sequencing). 

PMID- 24920304
TI  - A rice chloroplast transit peptide sequence does not alter the cytoplasmic
      localization of sheep serotonin N-acetyltransferase expressed in transgenic rice
      plants.
AB  - Ectopic overexpression of melatonin biosynthetic genes of animal origin has been
      used to generate melatonin-rich transgenic plants to examine the functional roles
      of melatonin in plants. However, the subcellular localization of these proteins
      expressed in the transgenic plants remains unknown. We studied the localization
      of sheep (Ovis aries) serotonin N-acetyltransferase (OaSNAT) and a translational
      fusion of a rice SNAT transit peptide to OaSNAT (TS:OaSNAT) in plants. Laser
      confocal microscopy analysis revealed that both OaSNAT and TS:OaSNAT proteins
      were localized to the cytoplasm even with the addition of the transit sequence to
      OaSNAT. Transgenic rice plants overexpressing the TS:OaSNAT fusion transgene
      exhibited high SNAT enzyme activity relative to untransformed wild-type plants,
      but lower activity than transgenic rice plants expressing the wild-type OaSNAT
      gene. Melatonin levels in both types of transgenic rice plant corresponded well
      with SNAT enzyme activity levels. The TS:OaSNAT transgenic lines exhibited
      increased seminal root growth relative to wild-type plants, but less than in the
      OaSNAT transgenic lines, confirming that melatonin promotes root growth. Seed
      specific OaSNAT expression under the control of a rice prolamin promoter did not
      confer high levels of melatonin production in transgenic rice seeds compared with
      seeds from transgenic plants expressing OaSNAT under the control of the
      constitutive maize ubiquitin promoter. 

PMID- 24920306
TI  - 'This diarrhoea is not a disease ...' local illness concepts and their effects on
      mothers' health seeking behaviour: a qualitative study, Shuhair, Yemen.
AB  - BACKGROUND: Globally, about seven million children under the age of five died in
      2011. Local illness concepts are thought to be related to inappropriate health
      seeking behaviour, and therefore, lead to child mortality. The aim of this study
      was to contribute to the definition of common local illness concepts with their
      effects on health-seeking behaviour for common childhood illnesses. METHODS: A
      qualitative focus group study was conducted between April 1 and 6, 2013.
      Participants were drawn purposefully from the vaccination unit at Shuhair Health
      Centre in Yemen. Four focus group discussions were conducted. The total number of
      participants was 31 mothers with at least one child under the age of five with a
      history of fever, diarrhoea, cough, or difficulty breathing during the 14 days
      preceding the study. Data was collected and analysed using micro-interlocutor
      analysis. RESULTS: The mean age of the participants was 31 years (SD +/- 4).
      There was remarkable concordance in local illness concepts across the focus
      groups. During focus group discussions, six local illness concepts (Senoon,
      lafkha, halib, didan, raqaba, and ayn) were mentioned. Local illness concepts
      determined the type of treatment. Most of these illnesses were not treated
      medically. Lafkha, halib, raqaba, and ayn were always classified as "not for
      medical treatment", whereas senoon and didan as sometimes "not for medical
      treatment". For medical symptoms, i.e. fever, diarrhoea, cough, and difficulty
      breathing, medical therapy was usually an option; these were classified as never
      or sometimes "not for medical treatment". Mothers trust in traditional medicine
      and believe that it is always beneficial and never harmful. The participants do
      not disclose traditional medicine use with their doctors because doctors oppose
      these practices and are not open enough to these types of treatment. CONCLUSIONS:
      Local illness concepts for common child illnesses are widespread, and they
      determine the type of treatment used. Interventions to improve children's health
      should use local illness concepts to educate parents. Traditional medicine as a
      treatment option in primary care should be considered.

PMID- 24920305
TI  - On the identification of potential regulatory variants within genome wide
      association candidate SNP sets.
AB  - BACKGROUND: Genome wide association studies (GWAS) are a population-scale
      approach to the identification of segments of the genome in which genetic
      variations may contribute to disease risk. Current methods focus on the discovery
      of single nucleotide polymorphisms (SNPs) associated with disease traits. As
      there are many SNPs within identified risk loci, and the majority of these are
      situated within non-coding regions, a key challenge is to identify and prioritize
      variants affecting regulatory sequences that are likely to contribute to the
      phenotype assessed. METHODS: We focused investigation on SNPs within lung and
      breast cancer GWAS loci that reached genome-wide significance for potential roles
      in gene regulation with a specific focus on SNPs likely to disrupt transcription
      factor binding sites. Within risk loci, the regulatory potential of sub-regions
      was classified using relevant open chromatin and epigenetic high throughput
      sequencing data sets from the ENCODE project in available cancer and normal cell
      lines. Furthermore, transcription factor affinity altering variants were
      predicted by comparison of position weight matrix scores between disease and
      reference alleles. Lastly, ChIP-seq data of transcription associated factors and
      topological domains were included as binding evidence and potential gene target
      inference. RESULTS: The sets of SNPs, including both the disease-associated
      markers and those in high linkage disequilibrium with them, were significantly
      over-represented in regulatory sequences of cancer and/or normal cells; however,
      over-representation was generally not restricted to disease-relevant tissue
      specific regions. The calculated regulatory potential, allelic binding affinity
      scores and ChIP-seq binding evidence were the three criteria used to prioritize
      candidates. Fitting all three criteria, we highlighted breast cancer
      susceptibility SNPs and a borderline lung cancer relevant SNP located in cancer
      specific enhancers overlapping multiple distinct transcription associated factor
      ChIP-seq binding sites. CONCLUSION: Incorporating high throughput sequencing
      epigenetic and transcription factor data sets from both cancer and normal cells
      into cancer genetic studies reveals potential functional SNPs and informs
      subsequent characterization efforts.

PMID- 24920307
TI  - Diagnosing unexplained fever: can quick diagnosis units replace inpatient
      hospitalization?
AB  - BACKGROUND: Outpatient quick diagnosis units (QDUs) have become an increasingly
      recognized alternative to hospitalization for the diagnosis of a number of
      potentially serious diseases. No study has prospectively evaluated the usefulness
      of QDU for the diagnosis of unexplained fever. MATERIALS AND METHODS: We
      prospectively assessed patients referred to QDU due to fever of uncertain nature
      (FUN), defined as a temperature > 38  degrees C during at least 1 week and no
      diagnosis after a previous evaluation. We also evaluated consecutive patients
      with FUN who were hospitalized during the same period. QDU and hospital costs
      were analysed by micro-costing techniques. RESULTS: We evaluated 176 QDU patients
      and 168 controls. QDU patients were younger and required fewer investigations
      than controls. QDU patients had higher prevalence of viral infections (36% vs.
      8%, P < 0.001) and lower prevalence of bacterial infections (6% vs. 46%, P <
      0.001) and malignancies (2% vs. 14%, P < 0.001). While time-to-diagnosis of QDU
      patients was longer than length-of-stay of controls (25.82 vs.12.89 days, P <
      0.001), 56% of QDU patients only required up to two visits. Cost per QDU patient
      was ?644.59, while it was ?4404.64 per hospitalized patient. CONCLUSIONS: QDU
      patients with FUN were younger and had less serious diseases than controls
      including more viral and less bacterial infections and fewer malignancies. Mainly
      owing to untimely diagnostic reports, time-to-diagnosis was longer in QDU
      patients. Cost-savings in QDU were substantial. Using objective tools to evaluate
      the condition severity and general health status of FUN patients could help
      decide the most appropriate setting for their diagnostic study.

PMID- 24920308
TI  - Superiority of frailty over age in predicting outcomes among geriatric trauma
      patients: a prospective analysis.
AB  - IMPORTANCE: The Frailty Index (FI) is a known predictor of adverse outcomes in
      geriatric patients. The usefulness of the FI as an outcome measure in geriatric
      trauma patients is unknown. OBJECTIVE: To assess the usefulness of the FI as an
      effective assessment tool in predicting adverse outcomes in geriatric trauma
      patients. DESIGN, SETTING, AND PARTICIPANTS: A 2-year (June 2011 to February
      2013) prospective cohort study at a level I trauma center at the University of
      Arizona. We prospectively measured frailty in all geriatric trauma patients.
      Geriatric patients were defined as those 65 years or older. The FI was calculated
      using 50 preadmission frailty variables. Frailty in patients was defined by an FI
      of 0.25 or higher. MAIN OUTCOMES AND MEASURES: The primary outcome measure was in
      hospital complications. The secondary outcome measure was adverse discharge
      disposition. In-hospital complications were defined as cardiac, pulmonary,
      infectious, hematologic, renal, and reoperation. Adverse discharge disposition
      was defined as discharge to a skilled nursing facility or in-hospital mortality.
      Multivariate logistic regression was used to assess the relationship between the
      FI and outcomes. RESULTS: In total, 250 patients were enrolled, with a mean (SD)
      age of 77.9 (8.1) years, median Injury Severity Score of 15 (range, 9-18), median
      Glasgow Coma Scale score of 15 (range, 12-15), and mean (SD) FI of 0.21 (0.10).
      Forty-four percent (n = 110) of patients had frailty. Patients with frailty were
      more likely to have in-hospital complications (odds ratio, 2.5; 95% CI, 1.5-6.0;
      P = .001) and adverse discharge disposition (odds ratio, 1.6; 95% CI, 1.1-2.4; P
      = .001). The mortality rate was 2.0% (n = 5), and all patients who died had
      frailty. CONCLUSIONS AND RELEVANCE: The FI is an independent predictor of in
      hospital complications and adverse discharge disposition in geriatric trauma
      patients. This index should be used as a clinical tool for risk stratification in
      this patient group.

PMID- 24920310
TI  - Boronate affinity monolith with a gold nanoparticle-modified hydrophilic polymer
      as a matrix for the highly specific capture of glycoproteins.
AB  - As low abundance is the great obstacle for glycoprotein analysis, the development
      of materials with high efficiency and selectivity for glycoprotein enrichment is
      a prerequisite in glycoproteome research. Herein, we report a new kind of
      hydrophilic boronate affinity monolith by attaching 4-mercaptophenylboronic acid
      (MPBA) with 2-mercaptoethylamine (MPA) on the gold nanoparticle-modified
      poly(glycidyl methacrylate-co-poly(ethylene glycol) diacrylate)) monolith for
      glycoprotein enrichment. With poly(ethylene glycol) diacrylate as the cross
      linker and the further modification of gold nanoparticles, the matrix has
      advantages of good hydrophilicity and enhanced surface area, which are beneficial
      to improve the enrichment selectivity and efficiency for glycoproteins. The
      attachment of MPBA and MPA provide intramolecular B?N coordination, which could
      further enhance the specificity of glycoprotein capture. Such a boronate affinity
      monolith was applied to enrich horseradish peroxidase (HRP) from the mixture of
      HRP and bovine serum albumin (BSA), and high selectivity was obtained even at a
      mass ratio of 1:1000. In addition, the binding capacity of ovalbumin on such
      monolith reached 390 MUg g(-1) . Furthermore, the average recovery of HRP on the
      prepared affinity monoliths was (84.8+/-1.9) %, obtained in three times
      enrichment with the same column. Finally, the boronate affinity monolith was
      successfully applied for the human-plasma glycoproteome analysis. As a result,
      160 glycoproteins were credibly identified from 9 MUg of human plasma,
      demonstrating the great potential of such a monolith for large-scale
      glycoproteome research. 

PMID- 24920311
TI  - Filaggrin gene mutations in African Americans with both ichthyosis vulgaris and
      atopic dermatitis.
AB  - Atopic dermatitis (AD) and ichthyosis vulgaris (IV) are two common disorders of
      epidermal homeostasis resulting in dry skin. The profilaggrin gene, located on
      chromosome 1q22, encodes a keratin filament aggregating protein (filaggrin) that
      is essential to forming the epidermal barrier and maintaining hydration. Null
      mutations in filaggrin have been found to underlie IV and are common in patients
      with AD, but the minority of African Americans with AD or IV show these mutations
      in filaggrin. We have selectively studied African Americans with both AD and IV
      to maximize the possibility of finding filaggrin null mutations in this
      population. DNA was collected using buccal swabs from 18 African American
      children with both AD and IV and 17 African American controls without either of
      these diseases. Purified genomic DNA was amplified using polymerase chain
      reaction from three regions of the filaggrin gene, exon 3, including R501X,
      2282del4, E2554X, R2447X, 1249insG, R826X, 2767insT, and E2422X. Of the African
      American children with both AD and IV, 22.2% were heterozygous for filaggrin null
      mutations. Out of the control group, one carried a null mutation and was later
      discovered to have a history of asthma. Null mutations found in this population
      included R501X (n = 1), 2282del4 (n = 2), and R826X (n = 2, including the control
      patient). Our data demonstrate a prevalence of filaggrin mutations in the African
      American population that exceeds previously published data, although the overall
      prevalence is still lower than in other populations. It is likely that factors
      other than known FLG mutations are involved in African American patients. 

PMID- 24920309
TI  - A role for human brain pericytes in neuroinflammation.
AB  - BACKGROUND: Brain inflammation plays a key role in neurological disease. Although
      much research has been conducted investigating inflammatory events in animal
      models, potential differences in human brain versus rodent models makes it
      imperative that we also study these phenomena in human cells and tissue. METHODS:
      Primary human brain cell cultures were generated from biopsy tissue of patients
      undergoing surgery for drug-resistant epilepsy. Cells were treated with pro
      inflammatory compounds IFNgamma, TNFalpha, IL-1beta, and LPS, and chemokines IP
      10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR.
      Microarray analysis was also performed on late passage cultures treated with
      vehicle or IFNgamma and IL-1beta. RESULTS: Early passage human brain cell
      cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes.
      Later passage cultures contained proliferating fibroblasts and pericytes only.
      Under basal culture conditions all cell types showed cytoplasmic NFkappaB
      indicating that they were in a non-activated state. Expression of IP-10 and MCP-1
      were significantly increased in response to pro-inflammatory stimuli. The two
      chemokines were expressed in mixed cultures as well as cultures of fibroblasts
      and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA
      and protein level, and both were secreted into cell culture media. NFkappaB
      nuclear translocation was also detected in response to pro-inflammatory cues
      (except IFNgamma) in all cell types. Microarray analysis of brain pericytes also
      revealed widespread changes in gene expression in response to the combination of
      IFNgamma and IL-1beta treatment including interleukins, chemokines, cellular
      adhesion molecules and much more. CONCLUSIONS: Adult human brain cells are
      sensitive to cytokine challenge. As expected 'classical' brain immune cells, such
      as microglia and astrocytes, responded to cytokine challenge but of even more
      interest, brain pericytes also responded to such challenge with a rich repertoire
      of gene expression. Immune activation of brain pericytes may play an important
      role in communicating inflammatory signals to and within the brain interior and
      may also be involved in blood brain barrier (BBB) disruption . Targeting brain
      pericytes, as well as microglia and astrocytes, may provide novel opportunities
      for reducing brain inflammation and maintaining BBB function and brain
      homeostasis in human brain disease.

PMID- 24920312
TI  - Gold-catalyzed diastereoselective cycloisomerization of alkylidene-cyclopropane
      bearing 1,6-diynes.
AB  - An unprecedented gold-catalyzed diastereoselective cycloisomerization of 1,6
      diynes bearing an alkylidene cyclopropane moiety has been developed. This
      methodology enables rapid access to a variety of 1,2-trimethylenenorbornanes,
      which are important building blocks in the preparations of abiotic and
      sesquiterpene core structures. 

PMID- 24920313
TI  - Chronic hypoxia increases arterial blood pressure and reduces adenosine and ATP
      induced vasodilatation in skeletal muscle in healthy humans.
AB  - AIMS: To determine the role played by adenosine, ATP and chemoreflex activation
      on the regulation of vascular conductance in chronic hypoxia. METHODS: The
      vascular conductance response to low and high doses of adenosine and ATP was
      assessed in ten healthy men. Vasodilators were infused into the femoral artery at
      sea level and then after 8-12 days of residence at 4559 m above sea level. At sea
      level, the infusions were carried out while the subjects breathed room air, acute
      hypoxia (FI O2 = 0.11) and hyperoxia (FI O2 = 1); and at altitude (FI O2 = 0.21
      and 1). Skeletal muscle P2Y2 receptor protein expression was determined in muscle
      biopsies after 4 weeks at 3454 m by Western blot. RESULTS: At altitude, mean
      arterial blood pressure was 13% higher (91 +/- 2 vs. 102 +/- 3 mmHg, P < 0.05)
      than at sea level and was unaltered by hyperoxic breathing. Baseline leg vascular
      conductance was 25% lower at altitude than at sea level (P < 0.05). At altitude,
      the high doses of adenosine and ATP reduced mean arterial blood pressure by 9
      12%, independently of FI O2 . The change in vascular conductance in response to
      ATP was lower at altitude than at sea level by 24 and 38%, during the low and
      high ATP doses respectively (P < 0.05), and by 22% during the infusion with high
      adenosine doses. Hyperoxic breathing did not modify the response to vasodilators
      at sea level or at altitude. P2Y2 receptor expression remained unchanged with
      altitude residence. CONCLUSIONS: Short-term residence at altitude increases
      arterial blood pressure and reduces the vasodilatory responses to adenosine and
      ATP.

PMID- 24920314
TI  - Transcriptomics assisted proteomic analysis of Nicotiana occidentalis infected by
      Candidatus Phytoplasma mali strain AT.
AB  - Phytoplasmas are pathogenic bacteria within the class of Mollicutes, which are
      associated with more than 1000 plant diseases. In this study, we applied
      quantitative mass spectrometry to analyse affected pathways of the model plant
      tobacco (Nicotiana occidentalis) upon Candidatus Phytoplasma mali strain AT
      infection. Using tissue obtained from leaf midribs, 1466 plant-assigned proteins
      were identified. For 1019 of these proteins, we could reproducibly quantify the
      expression changes of infected versus noninfected plants, of which 157 proteins
      were up- and 173 proteins were downregulated. Differential expression took place
      in a number of pathways, among others strong downregulation of porphyrin and
      chlorophyll metabolism and upregulation of alpha-linolenic acid metabolism, which
      was consistent with observed increased levels of jasmonic acid, a key signal
      molecule of plant defence. Our data shed light on the molecular networks that are
      involved in defence of plants against phytoplasma infection and provide a
      resource for further studies. 

PMID- 24920315
TI  - ZnO-Ag hybrids for ultrasensitive detection of trinitrotoluene by surface
      enhanced Raman spectroscopy.
AB  - An efficient and green approach was used to fabricate novel and low-cost surface
      enhanced Raman scattering (SERS) spectroscopy sensors based on 4-aminothiophenol
      (4-ATP) functionalized ZnO-Ag hybrid nanoflowers for the detection of explosives.
      Such SERS sensors exhibited high sensitivity to rhodamine 6G (R6G) at a low
      concentration of 10(-12) M and an enhancement factor of over 4.12 * 10(6) was
      achieved. Moreover, the Raman-inactive trinitrotoluene (TNT) initiated the high
      Raman scattering of non-resonated 4-ATP through the formation of a pi-donor-pi
      acceptor interaction between the pi-acceptor, TNT, and the pi-donor, the 4-ATP-Ag
      ZnO complex, on the flower-like hybrids. Because this pi-donor-pi-acceptor
      interaction could effectively induce the "hot spots" for SERS, TNT concentrations
      as low as 5 * 10(-9) M could be detected. Furthermore, other derivatives of TNT
      were also explored, and this sensor exhibited better selectivity for TNT than
      other similarly structured explosives. The low-cost hybrid SERS substrates
      presented good sensitivity and reproducibility for the analytes employed,
      demonstrating promising application in forensic science and homeland security. 

PMID- 24920317
TI  - The derivative discontinuity of the exchange-correlation functional.
AB  - The derivative discontinuity is a key concept in electronic structure theory in
      general and density functional theory in particular. The electronic energy of a
      quantum system exhibits derivative discontinuities with respect to different
      degrees of freedom that are a consequence of the integer nature of electrons. The
      classical understanding refers to the derivative discontinuity of the total
      energy as a function of the total number of electrons (N), but it can also
      manifest at constant N. Examples are shown in models including several hydrogen
      systems with varying numbers of electrons or nuclear charge (Z), as well as the 1
      dimensional Hubbard model (1DHM). Two sides of the problem are investigated:
      first, the failure of currently used approximate exchange-correlation functionals
      in DFT and, second, the importance of the derivative discontinuity in the exact
      electronic structure of molecules, as revealed by full configuration interaction
      (FCI). Currently, all approximate functionals, including hybrids, miss the
      derivative discontinuity, leading to basic errors that can be seen in many ways:
      from the complete failure to give the total energy of H2 and H2(+), to the
      missing gap in Mott insulators such as stretched H2 and the thermodynamic limit
      of the 1DHM, or a qualitatively incorrect density in the HZ molecule with two
      electrons and incorrect electron transfer processes. Description of the exact
      particle behaviour of electrons is emphasised, which is key to many important
      physical processes in real systems, especially those involving electron transfer,
      and offers a challenge for the development of new exchange-correlation
      functionals. 

PMID- 24920316
TI  - Prevalence of anxiety disorders among Finnish primary care high utilizers and
      validation of Finnish translation of GAD-7 and GAD-2 screening tools.
AB  - OBJECTIVE: To analyse the prevalence of GAD and other anxiety disorders, as well
      as sensitivity and specificity of GAD-7 among high utilizers of health care.
      SETTING: Four municipal health centres in Northern Finland. SUBJECTS: A
      psychiatric interview was conducted for 150 high utilizers of health care. MAIN
      OUTCOME MEASURES: Prevalence of GAD as well as sensitivity and specificity of GAD
      7. RESULTS: The prevalence of GAD was 4% in this study group of Finnish high
      utilizers of health care. The sensitivity of GAD-7 was 100.0% (95% CI 54.1-100.0)
      and the specificity of GAD-7 was 82.6% (95% CI 75.4-88.4) with a cut-off point of
      7 or more. CONCLUSION: GAD is rather common among high utilizers of primary care,
      although the prevalence of 4% is lower than that previously reported. GAD-7 is a
      valid and useful tool for detecting GAD among primary health care patients.

PMID- 24920318
TI  - Interfaces of dicationic ionic liquids and graphene: a molecular dynamics
      simulation study.
AB  - Molecular dynamics simulations were performed to investigate the interfacial
      structure and capacitance of electrical double layers (EDLs) in dicationic ionic
      liquids (DILs) 1-alkyl-3-dimethylimidazolium tetrafluoroborate [Cn(mim)2](BF4)2
      (n = 3, 6, 9), with respect to a baseline of a monocationic ionic liquid
      [C3mim][BF4], near planar carbon electrodes consisting of graphene sheets. The
      simulation results show that an adsorbed layer with double peaks is exclusively
      found for [C3(mim)2](BF4)2, while a single peak of the other three cations is
      observed at the neutral electrode, due to the difference in ion-wall interaction
      and cation-anion association. As the electrode becomes negatively charged, the
      second peak of [C3(mim)2](2+) is dramatically reduced, whereas those of
      [C6(mim)2](2+) and [C9(mim)2](2+) become non-trivial. The capacitance-potential
      curve of EDLs in DILs manifests a transition from camel shape to bell shape as
      the cation chain length increases, which is attributed to the enlargement of ion
      adsorption (per unit charge) on the electrode and the decrease of attractive
      interaction between ions.

PMID- 24920320
TI  - Variations of algal communities cause darkening of a Greenland glacier.
AB  - We have assessed the microbial ecology on the surface of Mittivakkat glacier in
      SE-Greenland during the exceptional high melting season in July 2012 when the so
      far most extreme melting rate for the Greenland Ice Sheet has been recorded. By
      employing a complementary and multi-disciplinary field sampling and analytical
      approach, we quantified the dramatic changes in the different microbial surface
      habitats (green snow, red snow, biofilms, grey ice, cryoconite holes). The
      observed clear change in dominant algal community and their rapidly changing cryo
      organic adaptation inventory was linked to the high melting rate. The changes in
      carbon and nutrient fluxes between different microbial pools (from snow to ice,
      cryoconite holes and glacial forefronts) revealed that snow and ice algae
      dominate the net primary production at the onset of melting, and that they have
      the potential to support the cryoconite hole communities as carbon and nutrient
      sources. A large proportion of algal cells is retained on the glacial surface and
      temporal and spatial changes in pigmentation contribute to the darkening of the
      snow and ice surfaces. This implies that the fast, melt-induced algal growth has
      a high albedo reduction potential, and this may lead to a positive feedback
      speeding up melting processes. 

PMID- 24920319
TI  - Inflammatory cues acting on the adult intestinal stem cells and the early onset
      of cancer (review).
AB  - The observation that cancer often arises at sites of chronic inflammation has
      prompted the idea that carcinogenesis and inflammation are deeply interwoven. In
      fact, the current literature highlights a role for chronic inflammation in
      virtually all the steps of carcinogenesis, including tumor initiation, promotion
      and progression. The aim of the present article is to review the current
      literature on the involvement of chronic inflammation in the initiation step and
      in the very early phases of tumorigenesis, in a type of cancer where adult stem
      cells are assumed to be the cells of origin of neoplasia. Since the
      gastrointestinal tract is regarded as the best-established model system to
      address the liaison between chronic inflammation and neoplasia, the focus of this
      article will be on intestinal cancer. In fact, the anatomy of the intestinal
      epithelial lining is uniquely suited to study adult stem cells in their niche,
      and the bowel crypt is an ideal developmental biology system, as proliferation,
      differentiation and cell migration are all distributed linearly along the long
      axis of the crypt. Moreover, crypt stem cells are regarded today as the most
      likely targets of neoplastic transformation in bowel cancer. More specifically,
      the present review addresses the molecular mechanisms whereby a state of chronic
      inflammation could trigger the neoplastic process in the intestine, focusing on
      the generation of inflammatory cues evoking enhanced proliferation in cells not
      initiated but at risk of neoplastic transformation because of their stemness.
      Novel experimental approaches, based on triggering an inflammatory stimulus in
      the neighbourhood of adult intestinal stem cells, are warranted to address some
      as yet unanswered questions. A possible approach, the targeted transgenesis of
      Paneth cells, may be aimed at 'hijacking' the crypt stem cell niche from a status
      characterized by the maintenance of homeostasis to local chronic inflammation,
      with the prospect of initiating neoplastic transformation in that site. 

PMID- 24920321
TI  - Relationship Between Triglyceride Tolerance, Body Mass Index, and Fat Depots in
      Hospitalized Patients Receiving Parenteral Nutrition.
AB  - BACKGROUND: Hypertriglyceridemia has been associated with adverse outcomes in
      patients receiving intravenous fat emulsions (IVFEs), but little is known about
      its prevalence and causes. MATERIALS AND METHODS: The study investigated whether
      a relationship exists between body mass index (BMI) and triglyceride tolerance in
      parenterally fed patients. We conducted a retrospective analysis of 287 adults
      receiving parenteral nutrition to determine whether patients with very low BMI
      (VLBMI, <16 kg/m(2)) tolerate IVFEs better than do patients with low BMI (LBMI,
      16-18.4 kg/m(2)), normal-weight patients (NBMI, 18.5-24.9 kg/m(2)), and
      overweight/obese patients (HBMI, >=25 kg/m(2)). RESULTS: The median triglyceride
      concentration during IVFE was significantly lower in VLBMI patients at 107 mg/dL
      compared with 124 mg/dL in non-VLBMI patients (P = .016), despite higher lipid
      infusion rates in the VLBMI group. There was a significant association between
      triglycerides and BMI in the aggregate cohort (R = 0.2375, P < .0001), with the
      highest frequency of hypertriglyceridemia occurring in HBMI patients despite
      relatively lower lipid and energy supply. In a subset of VLBMI patients (n = 36)
      who had an abdominal computed tomography scan, there was 25- to 100-fold
      variability in the size of the abdominal adipose tissue depots. In this subgroup,
      triglyceride concentrations correlated with visceral fat but not subcutaneous
      abdominal fat. CONCLUSIONS: In summary, patients with VLBMI have lower
      triglyceride concentrations during IVFEs than do other individuals, but there is
      considerable variability in triglycerides and body fat in this group. Caution
      should be employed with the use of IVFEs, especially in HBMI patients.

PMID- 24920322
TI  - Coronary microcirculation-a neglected target of cardioprotection.

PMID- 24920323
TI  - E1784K mutation in SCN5A and overlap syndrome.

PMID- 24920324
TI  - A survey of enoldiazo nucleophilicity in selective C-C bond forming reactions for
      the synthesis of natural product-like frameworks.
AB  - A survey of in situ, catalytically generated carbocations for coupling with
      enoldiazoacetate nucleophiles was performed. These couplings facilitate the rapid
      assembly of complex organodiazo compounds that provide a template for the
      synthesis of a variety of carbocyclic and heterocyclic ring systems. 

PMID- 24920325
TI  - Diagnosis and management of multiple paragangliomas of the head and neck.
AB  - Paragangliomas (PGs) are slowly growing, usually benign neoplasms. The aim of the
      study was to analyze the incidence, diagnostic and therapeutic management of
      patients with multiple paragangliomas of the head and neck. A retrospective
      review of the records of 84 patients with head and neck PGs, diagnosed and
      treated in our institution was performed for the years 1983-2013 to identify
      patients with multiple tumors. Fourteen (16.6 %) patients developed multiple PGs,
      synchronous or metachronous, within 4-21 years of follow-up. Clinical data of
      these patients were reviewed to evaluate the diagnosis, location, stage and
      management strategy. There was a total number of 37 tumors in 14 patients. There
      were 20/37 (54.0 %) carotid PGs, 9/37 (24.3 %) jugular PGs and 8/37 (21.7 %)
      vagal PGs. Carotid PGs were observed in 12/14 (86 %) patients and in 8/14 (57 %)
      cases bilateral tumors occurred. Vagal PGs developed in 7/14 (50 %) patients and
      bilateral tumors were found in 1/14 (7 %) case. Jugular PGs occurred in 9/14 (64
      %) patients. There were 30 synchronous tumors and seven metachronous PGs
      diagnosed 2-18 years after removal of the first tumor. Single metachronous
      mediastinal PG occurred. All patients had at least one tumor removed, with
      histopathological confirmation of the diagnosis. One patient had positive history
      of familial PGs. Carotid PGs are most common multiple paragangliomas.
      Radiological survey of the head and neck is required to detect multicentric
      tumors. Metachronous mediastinal and abdominal tumors may occur. Regular,
      prolonged follow-up is essential to identify metachronous PGs and possible
      postoperative gradual ICA occlusion.

PMID- 24920326
TI  - Vocal outcome after endoscopic thyroarytenoid myoneurectomy in patients with
      adductor spasmodic dysphonia.
AB  - Spasmodic dysphonia (SD) remains one of the most difficult of laryngeal
      pathologies to treat. With limited role for speech therapy, various surgical
      modalities have been tried with various success rates. The objective of the study
      is to report the results of vocal outcome after thyroarytenoid myoneurectomy in
      patients of adductor spasmodic dysphonia (ASD). 15 patients of ASD were selected.
      GRBAS, and voice handicap index (VHI) were used for perceptual evaluation of
      voice. Thyroarytenoid myoneurectomy was performed by vaporizing the muscular
      layer of the vocal fold with CO2 laser, at an intensity of 6 W with 1.2 mm
      diameter in scanner mode. Voice analysis was repeated at 12, 24 and 48 months
      follow-up. Preoperative GRBAS scores and VHI score of all the patients were poor.
      At 12 months 12/15 (80 %) patients having strain score of 0. There was marked
      improvement in VHI scores at 6 months. 10/15 (67 %) patients have been followed
      up for 24 months. 5/10 (50 %) patients have strain (S) value of 0. VHI scoring of
      5/10 (50 %) patients was <30. Two of the four patients completed 48 months follow
      up had a strain (S) value of 0, one patient has strain value of 1 and one patient
      had strain value of 2. 2/4 patients had VHI score of <30; one patient had that of
      40. Trans-oral CO2 laser thyroarytenoid myoneurectomy shows significant long-term
      improvement in voice quality in terms of reduced speech brakes, effort and strain
      in voice.

PMID- 24920327
TI  - Functional evolution of PLP-dependent enzymes based on active-site structural
      similarities.
AB  - Families of distantly related proteins typically have very low sequence identity,
      which hinders evolutionary analysis and functional annotation. Slowly evolving
      features of proteins, such as an active site, are therefore valuable for
      annotating putative and distantly related proteins. To date, a complete
      evolutionary analysis of the functional relationship of an entire enzyme family
      based on active-site structural similarities has not yet been undertaken.
      Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that
      diversified in the last universal ancestor. Using the comparison of protein
      active site structures (CPASS) software and database, we show that the active
      site structures of PLP-dependent enzymes can be used to infer evolutionary
      relationships based on functional similarity. The enzymes successfully clustered
      together based on substrate specificity, function, and three-dimensional-fold.
      This study demonstrates the value of using active site structures for functional
      evolutionary analysis and the effectiveness of CPASS.

PMID- 24920328
TI  - Influence of air stability and metabolic rate on exhaled flow.
AB  - The characteristics of contaminant transport and dispersion of exhaled flow from
      a manikin are thoroughly studied in this article with respect to the influence of
      two important factors: air stability conditions and metabolic rates. Four cases
      with the combinations of stable and neutral conditions as well as lower (1.2 met)
      and higher (2 met) metabolic rates for a breathing thermal manikin are employed.
      The exhaled contaminant is simulated by smoke and N2 O to visualize and measure
      the contaminant distribution both around and in front of the manikin. The results
      show that the microenvironment around the manikin body can be affected by
      different air distribution patterns and metabolic heating. Under stable
      conditions, the exhaled contaminant from mouth or nose is locked and stratified
      at certain heights, causing potentially high contaminant exposure to others. In
      addition, velocity profiles of the pulsating exhaled flow, which are normalized
      by mean peak velocities, present similar shapes to a steady jet. The outlet
      velocity close to the mouth shows decrement with both exhalation temperature and
      body plume. The velocity decay and concentration decay also show significant
      dependence on air stability and metabolic level. 

PMID- 24920329
TI  - Rewiring Host Lipid Metabolism by Large Viruses Determines the Fate of Emiliania
      huxleyi, a Bloom-Forming Alga in the Ocean.
AB  - Marine viruses are major ecological and evolutionary drivers of microbial food
      webs regulating the fate of carbon in the ocean. We combined transcriptomic and
      metabolomic analyses to explore the cellular pathways mediating the interaction
      between the bloom-forming coccolithophore Emiliania huxleyi and its specific
      coccolithoviruses (E. huxleyi virus [EhV]). We show that EhV induces profound
      transcriptome remodeling targeted toward fatty acid synthesis to support viral
      assembly. A metabolic shift toward production of viral-derived sphingolipids was
      detected during infection and coincided with downregulation of host de novo
      sphingolipid genes and induction of the viral-encoded homologous pathway. The
      depletion of host-specific sterols during lytic infection and their detection in
      purified virions revealed their novel role in viral life cycle. We identify an
      essential function of the mevalonate-isoprenoid branch of sterol biosynthesis
      during infection and propose its downregulation as an antiviral mechanism. We
      demonstrate how viral replication depends on the hijacking of host lipid
      metabolism during the chemical "arms race" in the ocean.

PMID- 24920330
TI  - A Scalable Open-Source Pipeline for Large-Scale Root Phenotyping of Arabidopsis.
AB  - Large-scale phenotyping of multicellular organisms is one of the current
      challenges in biology. We present a comprehensive and scalable pipeline that
      allows for the efficient phenotyping of root growth traits on a large scale. This
      includes a high-resolution, low-cost acquisition setup as well as the automated
      image processing software BRAT. We assess the performance of this pipeline in
      Arabidopsis thaliana under multiple growth conditions and show its utility by
      performing genome-wide association studies on 16 root growth traits quantified by
      BRAT each day during a 5-d time-course experiment. The most significantly
      associated genome region for root growth rate is a locus encoding a calcium
      sensing receptor. We find that loss of function and overexpression of this gene
      can significantly alter root growth in a growth condition dependent manner and
      that the minor natural allele of the Calcium Sensor Receptor locus is highly
      significantly enriched in populations in coastal areas, demonstrating the power
      of our approach to identify regulators of root growth that might have adaptive
      relevance.

PMID- 24920331
TI  - Polycomb-Group Proteins and FLOWERING LOCUS T Maintain Commitment to Flowering in
      Arabidopsis thaliana.
AB  - The switch from vegetative to reproductive growth is extremely stable even if
      plants are only transiently exposed to environmental stimuli that trigger
      flowering. In the photoperiodic pathway, a mobile signal, florigen, encoded by
      FLOWERING LOCUS T (FT) in Arabidopsis thaliana, induces flowering. Because FT
      activity in leaves is not maintained after transient photoperiodic induction, the
      molecular basis for stable floral commitment is unclear. Here, we show that
      Polycomb-group (Pc-G) proteins, which mediate epigenetic gene regulation,
      maintain the identity of inflorescence and floral meristems after floral
      induction. Thus, plants with reduced Pc-G activity show a remarkable increase of
      cauline leaves under noninductive conditions and floral reversion when shifted
      from inductive to noninductive conditions. These phenotypes are almost completely
      suppressed by loss of FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE, which
      both delay flowering and promote vegetative shoot identity. Upregulation of FLC
      in Pc-G mutants leads to a strong decrease of FT expression in inflorescences. We
      find that this activity of FT is needed to prevent floral reversion.
      Collectively, our results reveal that floral meristem identity is at least
      partially maintained by a daylength-independent role of FT whose expression is
      indirectly sustained by Pc-G activity.

PMID- 24920332
TI  - REPRESSOR OF SILENCING5 Encodes a Member of the Small Heat Shock Protein Family
      and Is Required for DNA Demethylation in Arabidopsis.
AB  - In Arabidopsis thaliana, active DNA demethylation is initiated by the DNA
      glycosylase REPRESSOR OF SILENCING1 (ROS1) and its paralogs DEMETER, DEMETER
      LIKE2 (DML2), and DML3. How these demethylation enzymes are regulated, however,
      is poorly understood. Here, using a transgenic Arabidopsis line harboring the
      stress-inducible RESPONSIVE TO DEHYDRATION29A (RD29A) promoter-LUCIFERASE (LUC)
      reporter gene and the cauliflower mosaic virus 35S promoter (35S)-NEOMYCIN
      PHOSPHOTRANSFERASE II (NPTII) antibiotic resistance marker gene, we characterize
      a ROS locus, ROS5, that encodes a protein in the small heat shock protein family.
      ROS5 mutations lead to the silencing of the 35S-NPTII transgene due to DNA
      hypermethylation but do not affect the expression of the RD29A-LUC transgene.
      ROS5 physically interacts with the histone acetyltransferase ROS4/INCREASED DNA
      METHYLATION1 (IDM1) and is required to prevent the DNA hypermethylation of some
      genes that are also regulated by ROS1 and IDM1. We propose that ROS5 regulates
      DNA demethylation by interacting with IDM1, thereby creating a chromatin
      environment that facilitates the binding of ROS1 to erase DNA methylation.

PMID- 24920333
TI  - The Chromatin-Remodeling Factor PICKLE Integrates Brassinosteroid and Gibberellin
      Signaling during Skotomorphogenic Growth in Arabidopsis.
AB  - Plant cell elongation is controlled by endogenous hormones, including
      brassinosteroid (BR) and gibberellin (GA), and by environmental factors, such as
      light/darkness. The molecular mechanisms underlying the convergence of these
      signals that govern cell growth remain largely unknown. We previously showed that
      the chromatin-remodeling factor PICKLE/ENHANCED PHOTOMORPHOGENIC1 (PKL/EPP1)
      represses photomorphogenesis in Arabidopsis thaliana. Here, we demonstrated that
      PKL physically interacted with PHYTOCHROME-INTERACTING FACTOR3 (PIF3) and
      BRASSINAZOLE-RESISTANT1 (BZR1), key components of the light and BR signaling
      pathways, respectively. Also, this interaction promoted the association of PKL
      with cell elongation-related genes. We found that PKL, PIF3, and BZR1 coregulate
      skotomorphogenesis by repressing the trimethylation of histone H3 Lys-27
      (H3K27me3) on target promoters. Moreover, DELLA proteins interacted with PKL and
      attenuated its binding ability. Strikingly, brassinolide and GA3 inhibited
      H3K27me3 modification of histones associated with cell elongation-related loci in
      a BZR1- and DELLA-mediated manner, respectively. Our findings reveal that the PKL
      chromatin-remodeling factor acts as a critical node that integrates
      light/darkness, BR, and GA signals to epigenetically regulate plant growth and
      development. This work also provides a molecular framework by which hormone
      signals regulate histone modification in concert with light/dark environmental
      cues.

PMID- 24920335
TI  - Deficient sucrose synthase activity in developing wood does not specifically
      affect cellulose biosynthesis, but causes an overall decrease in cell wall
      polymers.
AB  - The biosynthesis of wood in aspen (Populus) depends on the metabolism of sucrose,
      which is the main transported form of carbon from source tissues. The largest
      fraction of the wood biomass is cellulose, which is synthesized from UDP-glucose.
      Sucrose synthase (SUS) has been proposed previously to interact directly with
      cellulose synthase complexes and specifically supply UDP-glucose for cellulose
      biosynthesis. To investigate the role of SUS in wood biosynthesis, we
      characterized transgenic lines of hybrid aspen with strongly reduced SUS activity
      in developing wood. No dramatic growth phenotypes in glasshouse-grown trees were
      observed, but chemical fingerprinting with pyrolysis-GC/MS, together with
      micromechanical analysis, showed notable changes in chemistry and ultrastructure
      of the wood in the transgenic lines. Wet chemical analysis showed that the dry
      weight percentage composition of wood polymers was not changed significantly.
      However, a decrease in wood density was observed and, consequently, the content
      of lignin, hemicellulose and cellulose was decreased per wood volume. The
      decrease in density was explained by a looser structure of fibre cell walls as
      shown by increased wall shrinkage on drying. The results show that SUS is not
      essential for cellulose biosynthesis, but plays a role in defining the total
      carbon incorporation to wood cell walls. 

PMID- 24920336
TI  - Combination of aloe-emodin with radiation enhances radiation effects and improves
      differentiation in human cervical cancer cells.
AB  - The aim of the present study was to investigate the effects of aloe-emodin (AE)
      on the radiosensitivity and differentiation of HeLa human cervical cancer cells.
      Cell proliferation was assessed in the HeLa cervical cancer cell line by a
      methylthiazolyldiphenyl-tetrazolium bromide assay. Radiosensitivity was
      determined by a colony-forming assay. Flow cytometry was used for analysis of
      cell cycle distribution and apoptosis. The expression of gamma-H2AX and cyclin B
      was assessed by western blotting. Alkaline phosphatase (ALP) activity was
      measured by an ALP activity kit. It was demonstrated that AE inhibited the
      proliferation of HeLa cells in a concentration- and time-dependent manner,
      induced G2/M and S phase cell cycle arrest and enhanced the radiosensitivity of
      HeLa cells. The combination of AE and radiation induced apoptosis, upregulated
      cyclin B and gamma-H2AX expression and further improved ALP activity compared
      with treatment with AE or radiation alone. AE enhanced the radiosensitivity of
      HeLa human cervical cancer cells in vitro, inhibited the proliferation of HeLa
      cells, induced G2/M phase cell cycle arrest and, in combination with radiation,
      induced the apoptosis and improved the differentiation of HeLa cells. 

PMID- 24920334
TI  - Intervention of Phytohormone Pathways by Pathogen Effectors.
AB  - The constant struggle between plants and microbes has driven the evolution of
      multiple defense strategies in the host as well as offense strategies in the
      pathogen. To defend themselves from pathogen attack, plants often rely on
      elaborate signaling networks regulated by phytohormones. In turn, pathogens have
      adopted innovative strategies to manipulate phytohormone-regulated defenses.
      Tactics frequently employed by plant pathogens involve hijacking, evading, or
      disrupting hormone signaling pathways and/or crosstalk. As reviewed here, this is
      achieved mechanistically via pathogen-derived molecules known as effectors, which
      target phytohormone receptors, transcriptional activators and repressors, and
      other components of phytohormone signaling in the host plant. Herbivores and sap
      sucking insects employ obligate pathogens such as viruses, phytoplasma, or
      symbiotic bacteria to intervene with phytohormone-regulated defenses. Overall, an
      improved understanding of phytohormone intervention strategies employed by pests
      and pathogens during their interactions with plants will ultimately lead to the
      development of new crop protection strategies.

PMID- 24920337
TI  - Global and regional kinematics of the cervical spine during upper cervical spine
      manipulation: a reliability analysis of 3D motion data.
AB  - Studies reporting spine kinematics during cervical manipulation are usually
      related to continuous global head-trunk motion or discrete angular displacements
      for pre-positioning. To date, segmental data analyzing continuous kinematics of
      cervical manipulation is lacking. The objective of this study was to investigate
      upper cervical spine (UCS) manipulation in vitro. This paper reports an inter-
      and intra-rater reliability analysis of kinematics during high velocity low
      amplitude manipulation of the UCS. Integration of kinematics into specific
      subject 3D models has been processed as well for providing anatomical motion
      representation during thrust manipulation. Three unembalmed specimens were
      included in the study. Restricted dissection was realized to attach technical
      clusters to each bone of interest (skull, C1-C4 and sternum). During
      manipulation, bone motion data was computed using an optoelectronic system. The
      reliability of manipulation kinematics was assessed for three experimented
      practitioners performing two trials of 3 repetitions on two separate days. During
      UCS manipulation, average global head-trunk motion ROM (+/-SD) were 14 +/- 5
      degrees , 35 +/- 7 degrees  and 14 +/- 8 degrees  for lateral bending, axial
      rotation and flexion-extension, respectively. For regional ROM (C0-C2),
      amplitudes were 10 +/- 5 degrees , 30 +/- 5 degrees  and 16 +/- 4 degrees  for
      the same respective motions. Concerning the reliability, mean RMS ranged from 1
      degrees  to 4 degrees  and from 3 degrees  to 6 degrees  for intra- and inter
      rater comparisons, respectively. The present results confirm the limited angular
      displacement during manipulation either for global head-trunk or for UCS motion
      components, especially for axial rotation. Additionally, kinematics variability
      was low confirming intra- and inter-practitioners consistency of UCS manipulation
      achievement. 

PMID- 24920339
TI  - Diversity and community structure of fungi through a permafrost core profile from
      the Qinghai-Tibet Plateau of China.
AB  - While a vast number of studies have addressed the prokaryotic diversity in
      permafrost, characterized by subzero temperatures, low water activity, and
      extremely low rates of nutrient and metabolite transfer, fungal patterns have
      received surprisingly limited attention. Here, the fungal diversity and community
      structure were investigated by culture-dependent technique combined with cloning
      restriction fragment length polymorphism (RFLP) analysis of sediments in a 10-m
      long permafrost core from the Qinghai-Tibet Plateau of China. A total of 62
      fungal phylotypes related to 10 distinct classes representing three phyla were
      recovered from 5031 clones generated in 13 environmental gene libraries. A large
      proportion of the phylotypes (25/62) that were distantly related to described
      fungal species appeared to be novel diversity. Ascomycota was the predominant
      group of fungi, with respect to both clone and phylotype number. Our results
      suggested there was the existence of cosmopolitan psychrophilic or
      psychrotolerant fungi in permafrost sediments, the community composition of fungi
      varied with increasing depth, while these communities largely distributed
      according to core layers. 

PMID- 24920338
TI  - TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with
      HnRNP A2/B1.
AB  - Nucleotide repeat expansions can elicit neurodegeneration as RNA by sequestering
      specific RNA-binding proteins, preventing them from performing their normal
      functions. Conversely, mutations in RNA-binding proteins can trigger
      neurodegeneration at least partly by altering RNA metabolism. In Fragile X
      associated tremor/ataxia syndrome (FXTAS), a CGG repeat expansion in the 5'UTR of
      the fragile X gene (FMR1) leads to progressive neurodegeneration in patients and
      CGG repeats in isolation elicit toxicity in Drosophila and other animal models.
      Here, we identify the amyotrophic lateral sclerosis (ALS)-associated RNA-binding
      protein TAR DNA-binding protein (TDP-43) as a suppressor of CGG repeat-induced
      toxicity in a Drosophila model of FXTAS. The rescue appears specific to TDP-43,
      as co-expression of another ALS-associated RNA-binding protein, FUS, exacerbates
      the toxic effects of CGG repeats. Suppression of CGG RNA toxicity was abrogated
      by disease-associated mutations in TDP-43. TDP-43 does not co-localize with CGG
      RNA foci and its ability to bind RNA is not required for rescue. TDP-43-dependent
      rescue does, however, require fly hnRNP A2/B1 homologues Hrb87F and Hrb98DE.
      Deletions in the C-terminal domain of TDP-43 that preclude interactions with
      hnRNP A2/B1 abolish TDP-43-dependent rescue of CGG repeat toxicity. In contrast,
      suppression of CGG repeat toxicity by hnRNP A2/B1 is not affected by RNAi
      mediated knockdown of the fly TDP-43 orthologue, TBPH. Lastly, TDP-43 suppresses
      CGG repeat-triggered mis-splicing of an hnRNP A2/B1-targeted transcript. These
      data support a model in which TDP-43 suppresses CGG-mediated toxicity through
      interactions with hnRNP A2/B1 and suggest a convergence of pathogenic cascades
      between repeat expansion disorders and RNA-binding proteins implicated in
      neurodegenerative disease. 

PMID- 24920340
TI  - Failure processes in embedded monolayer graphene under axial compression.
AB  - Exfoliated monolayer graphene flakes were embedded in a polymer matrix and loaded
      under axial compression. By monitoring the shifts of the 2D Raman phonons of
      rectangular flakes of various sizes under load, the critical strain to failure
      was determined. Prior to loading care was taken for the examined area of the
      flake to be free of residual stresses. The critical strain values for first
      failure were found to be independent of flake size at a mean value of -0.60%
      corresponding to a yield stress up to -6 GPa. By combining Euler mechanics with a
      Winkler approach, we show that unlike buckling in air, the presence of the
      polymer constraint results in graphene buckling at a fixed value of strain with
      an estimated wrinkle wavelength of the order of 1-2 nm. These results were
      compared with DFT computations performed on analogue coronene/PMMA oligomers and
      a reasonable agreement was obtained.

PMID- 24920341
TI  - A cresyl violet-based fluorescent off-on probe for the detection and imaging of
      hypoxia and nitroreductase in living organisms.
AB  - A new cresyl violet-based fluorescent off-on probe has been developed through a
      one-step synthesis for the detection of nitroreductase (NTR) and hypoxia. The
      detection mechanism is based on the NTR-catalyzed reduction of the probe to
      cresyl violet, accompanied with a large fluorescence enhancement at a long
      wavelength of 625 nm. The probe can detect NTR in aqueous solution with high
      selectivity and sensitivity, and the detection limit is 1 ng mL(-1) NTR. Most
      importantly, the probe has been successfully used to image not only NTR and
      hypoxia in living cells, but also the distribution of NTR in zebrafish in vivo. 

PMID- 24920343
TI  - Perceived HIV status is a key determinant of unprotected anal intercourse within
      partnerships of men who have sex with men in Amsterdam.
AB  - The practice of unprotected anal intercourse (UAI) involves at least two
      partners. We examined the associations between insertive or receptive UAI and
      perceived HIV seroconcordance and partnership type in self-perceived HIV-negative
      and self-perceived HIV-positive men who have sex with men (MSM). MSM (age >= 18
      years) were recruited for a cross-sectional survey at the sexually transmitted
      infections clinic in Amsterdam, the Netherlands, in 2008-2009. Participants
      completed a questionnaire concerning partnerships in the preceding 6 months.
      Associations were quantified via multinomial logistic regression models using
      generalized estimating equations. The outcomes were 'no, or safe anal
      intercourse', 'insertive UAI', and 'receptive UAI'. We included 5,456
      partnerships from 1,890 self-perceived HIV-negative men and 1,861 partnerships
      from 558 self-perceived HIV-positive men. Within the partnerships, perceived HIV
      status of the partner was an important determinant of UAI (p < 0.001). Among HIV
      negative men, perceived HIV discordance was negatively associated with receptive
      UAI compared with no or safe UAI (OR 0.57; 95 % CI 0.36-0.92); when the partners
      were more familiar with each other, the risk of receptive UAI was increased
      relative to no or safe anal intercourse. Among HIV-positive men, perceived HIV
      discordance was negatively associated with insertive UAI (OR 0.05; 95 % CI 0.03
      0.08). Within partnerships, perceived HIV status of the partner was one of the
      strongest determinants of UAI among self-perceived HIV-negative and HIV-positive
      MSM, and discordant serostatus was negatively associated with UAI. The findings
      suggest that serosorting is one of the main strategies when engaging in UAI.

PMID- 24920345
TI  - Between porphyrins and phthalocyanines: 10,20-diaryl-5,15
      tetrabenzodiazaporphyrins.
AB  - meso-Diaryltetrabenzo(opp)diazaporphyrins are made readily available via Curtius
      rearrangement of azidocarbonyl derivatives of meso-aryldibenzodipyrromethenes,
      readily generated with or without isolation from tert-butoxycarbonyl derivatives
      of the same system. The new tetrapyrrolic dyes are isostructural with 5,15
      diaryltetrabenzoporphyrins and resemble both phthalocyanines and
      tetrabenzoporphyrins to afford an interesting new system for optical applications
      and material research. 

PMID- 24920344
TI  - Earlier anal sexarche and co-occurring sexual risk are associated with current
      HIV-related risk behaviors among an online sample of men who have sex with men in
      Asia.
AB  - Studies of heterosexual populations across the globe and men who have sex with
      men (MSM) in a few developed countries showed that earlier sexual debut
      (sexarche) was associated with higher levels of co-occurring and subsequent HIV
      risk behaviors. We examined the relationships between earlier anal sexarche,
      unprotected earlier anal sexarche and current HIV risks among MSM from Asia. A
      cross-sectional online survey was conducted among MSM (N = 10,826) in Asia in
      2010. Bivariate and multivariable logistic regressions were used to identify co
      occurring (i.e., sexual experiences during sexarche) and current HIV-related risk
      factors (i.e., past 6 months) associated with earlier anal sexarche (before the
      age of 18) and unprotected earlier anal sexarche, respectively. Earlier anal
      sexarche was significantly associated with lack of condom use, being anal
      receptive or both receptive and insertive, and having a partner who were older
      during sexarche. It was also associated with current HIV-related risk behaviors
      including having multiple male sexual partners, having been paid for sex, and
      increased frequencies of recreational drug use. Unprotected earlier anal sexarche
      was significantly associated with inconsistent condom use in the past the 6
      months. Improved and culturally sensitive sex education at schools should be
      included in national and regional HIV/AIDS prevention programming and policies in
      Asia. Such sex education programs should incorporate curriculum that address
      sexuality, sexual orientation, and sexual behaviors beyond those related to
      reproductive health.

PMID- 24920342
TI  - Individual and socio-environmental factors associated with unsafe injection
      practices among young adult injection drug users in San Diego.
AB  - Unsafe injection practices significantly increase the risk of hepatitis C virus
      (HCV) and human immunodeficiency virus (HIV) infection among injection drug users
      (IDUs). We examined individual and socio-environmental factors associated with
      unsafe injection practices in young adult IDUs in San Diego, California. Of 494
      IDUs, 46.9 % reported receptive syringe sharing and 68.8 % sharing drug
      preparation paraphernalia in the last 3 months. Unsafe injection practices were
      associated with increased odds of having friends who injected drugs with used
      syringes, injecting with friends or sexual partners, and injecting heroin.
      Perceived high susceptibility to HIV and perceived barriers to obtaining sterile
      syringes were associated with increased odds of receptive syringe sharing, but
      not with sharing injection paraphernalia. Over half the IDUs reported unsafe
      injection practices. Our results suggest that personal relationships might
      influence IDUs' perceptions that dictate behavior. Integrated interventions
      addressing individual and socio-environmental factors are needed to promote safe
      injection practices in this population.

PMID- 24920346
TI  - [Endoscopic vacuum therapy of perforations and anastomotic insufficiency of the
      esophagus].
AB  - BACKGROUND: The high morbidity and mortality of esophageal defects show that the
      clinical challenge in the treatment of this disease still remains. An innovative
      method which has been developed in recent years for esophageal leakage is
      endoscopic vacuum therapy. OBJECTIVES: A retrospective analysis of all patients
      treated for esophageal perforation with endoscopic vacuum therapy in our
      department was carried out. METHODS: From November 2006 to October 2013 a total
      of 35 patients were treated with this method and of these 21 had anastomotic
      leakage, 7 had iatrogenic perforation due to flexible or rigid endoscopy and 7
      patients had esophageal defects of various other origins. Drainage systems with
      an open pore polyurethane tip were placed using a standard endoscope. The vacuum
      drainage may be positioned either in the esophageal lumen onto the defect or
      through the defect into the extraluminal wound cavity. The intraluminal or
      intracavitary vacuum drainage is connected to an electronically controlled vacuum
      device and a continuous negative pressure of 125 mmHg is maintained for several
      days. The esophageal lumen or wound cavity collapses around the drainage
      resulting in intraluminal evacuation and closure of the defect. Under endoscopic
      monitoring the vacuum system is changed regularly until stable secondary healing
      of the intracorporeal wound or closure of the transmural defect is achieved.
      RESULTS: In 32 out of 35 patients (91.4 %) healing of defects was achieved after
      median treatment duration of 11 days (range 4-78 days). The postoperative
      anastomotic leakage healed in 20 out of 21 patients (95.2 %) after a median of 11
      days (range 4-46 days) of therapy. The defects in the 7 patients who were treated
      for iatrogenic perforation all healed (100 %) after a median treatment time of 5
      days (range 4-7 days). There was one case of a recurrent fistula 75 days after
      treatment. The 90-day mortality in this series of 35 patients was 5.7 %.
      DISCUSSION: The results of this retrospective study emphasize the increasing
      importance of endoscopic vacuum therapy in the current literature as an
      endoscopic treatment method in the management of esophageal perforation and
      anastomotic leakage.

PMID- 24920347
TI  - Effects of acute hypoxia on heart rate variability, sample entropy and
      cardiorespiratory phase synchronization.
AB  - BACKGROUND: Investigating the responses of autonomic nervous system (ANS) in
      hypoxia may provide some knowledge about the mechanism of neural control and
      rhythmic adjustment. The integrated cardiac and respiratory system display
      complicated dynamics that are affected by intrinsic feedback mechanisms
      controlling their interaction. To probe how the cardiac and respiratory system
      adjust their rhythms in different simulated altitudes, we studied heart rate
      variability (HRV) in frequency domain, the complexity of heartbeat series and
      cardiorespiratory phase synchronization (CRPS) between heartbeat intervals and
      respiratory cycles. METHODS: In this study, twelve male subjects were exposed to
      simulated altitude of sea level, 3000 m and 4000 m in a hypobaric chamber. HRV
      was assessed by power spectral analysis. The complexity of heartbeat series was
      quantified by sample entropy (SampEn). CRPS was determined by cardiorespiratory
      synchrogram. RESULTS: The power spectral HRV indices at all frequency bands
      depressed according to the increase of altitude. The SampEn of heartbeat series
      increased significantly with the altitude (P < 0.01). The duration of CRPS epochs
      at 3000 m was not significantly different from that at sea level. However, it was
      significantly longer at 4000 m (P < 0.01). CONCLUSIONS: Our results suggest the
      phenomenon of CRPS exists in normal subjects when they expose to acute hypoxia.
      Further, the autonomic regulation has a significantly stronger influence on CRPS
      in acute hypoxia. The changes of CRPS and HRV parameters revealed the different
      regulatory mechanisms of the cardiac and respiratory system at high altitude.

PMID- 24920348
TI  - Anterior fontanelle closure and size in full-term children based on head computed
      tomography.
AB  - INTRODUCTION: This study investigates radiographically acquired normative ranges
      of anterior fontanelle closure (AFC) and surface area (SA) in healthy full-term
      infants. METHODS: High-resolution head computed tomography (CT) scans were
      retrospectively reviewed for AFC and AF dimensions to allow approximation of AF
      SA. RESULTS: Between 15 and 23 head CT scans per monthly age-group (0-24 months)
      were reviewed, totaling 464 scans. AFC frequency increased steadily from age 10
      (16%) to 20 months (88%), reaching higher than 50% at age 16 months (53%). The AF
      was closed in 3% to 5% of infants at 5 to 6 months. AF median SA increased from
      769.3 mm(2) (age 0 months) to 1022.2 mm(2) (2 months), then declined steadily.
      CONCLUSIONS: This study provides reference charts detailing AFC frequency and AF
      SA as a function of age. Wide variability of AFC timing and AF size among healthy
      infants suggest that early or delayed AFC may represent normal variants.

PMID- 24920349
TI  - Efficacy and safety of the pulsed infusions of levosimendan in outpatients with
      advanced heart failure (LevoRep) study: a multicentre randomized trial.
AB  - AIMS: The aim of this study was to determine whether intermittent ambulatory
      treatment with levosimendan would improve functional capacity, quality of life,
      and event-free survival in patients with advanced heart failure. METHODS AND
      RESULTS: This was a prospective, randomized, double-blind, placebo-controlled,
      multicentre, parallel-group trial of pulsed infusions of levosimendan in 120
      outpatients with advanced heart failure (EF <=35%, NYHA class III or IV). The
      study was conducted at 11 centres in Austria, Greece, and Germany. Levosimendan
      (0.2 ug/kg/min) or placebo was administered for 6 h at 2-week intervals over 6
      weeks, in addition to standard care therapy. The primary outcome was the
      proportion of patients with a >=20% improvement in the 6 min walk test and a
      >=15% score increase on the Kansas City Cardiomyopathy Questionnaire at the end
      of the 24-week study period. Secondary outcomes included event-free survival
      after 24 weeks. Analyses were performed on an intention-to-treat basis. The
      primary endpoint was reached in 19% of patients receiving levosimendan and 15.8%
      of patients receiving placebo (odds ratio 1.25; 95% confidence interval 0.44
      3.59; P = 0.810). Cardiac death (four vs. one), heart transplants (two vs. one),
      and acute heart failure (14 vs. nine) were more frequent with placebo as compared
      with levosimendan. The incidence of side effects was comparable between groups.
      CONCLUSION: Intermittent ambulatory treatment with levosimendan in patients with
      advanced heart failure did not improve significantly functional capacity or
      quality of life as compared with placebo. An adequately powered, event-driven
      trial is warranted to enlarge on our findings. TRIAL REGISTRATION: NCT01065194.

PMID- 24920350
TI  - The career path choices of veterinary radiologists.
AB  - Concerns of a shortage of board certified specialists willing to work in academia
      have shadowed the medical and veterinary communities for decades. As a result, a
      number of studies have been conducted to determine how to foster, attract, and
      retain specialists in academia. More recently, there has been a growing
      perception that it is difficult for academic institutions to hire board certified
      veterinary radiologists. The objective of this study was to describe the career
      paths (academia vs. private sector) of veterinary radiologists and to determine
      what factors influenced their career path decisions. A mixed mode cross-sectional
      survey was used to survey ACVR radiologists and residents-in-training, 48%
      (255/529) of which responded. There was a near unidirectional movement of
      radiologists from academia to the private sector: 45.7% (59/129) of the
      respondents who began their careers in academia had switched to the private
      sector while only 8% (7/88) had left the private sector for academia. If a
      shortage of academic radiologists exists, then perhaps the issue should be framed
      as a problem with retention vs. recruitment. The most influential factors in the
      decision to leave academia were remuneration (wages and benefits), lack of
      interest/enjoyment in research, geographical location, and family considerations.
      It is salient that average salaries increased by twofold after leaving academia
      for the private sector. 

PMID- 24920351
TI  - Magnetic resonance imaging in the evaluation of cognitive function.
AB  - Image quality of magnetic resonance imaging (MRI) scans of the brain currently
      approximate gross anatomy as would be viewed at autopsy. During the first decade
      of the 21st Century incredible advances in image processing and quantification
      have occurred permitting more refined methods for studying brain-behavior
      cognitive functioning. The current presentation overviews the current status of
      MRI methods for routine clinical assessment of brain pathology, how these
      techniques identify neuropathology and how pathological findings are quantified.
      Diffusion tensor imaging (DTI), functional MRI (fMRI), and resting state fMRI are
      all reviewed, emphasizing how these techniques permit an examination of brain
      function and connectivity. General regional relationships of brain function
      associated with cognitive control will be highlighted.

PMID- 24920352
TI  - Association between the lengths of GT dinucleotide repeat in the PIK3CA gene with
      breast cancer risk.
AB  - The phosphatidylinositol 3-kinase (PI3 K)/Akt signaling pathway is one of the
      most commonly mutated pathways in breast cancer. To date, there has been no study
      on polymorphism of phosphatidylinositol-3,4-bisphosphonate 3-kinase, catalytic
      subunit alpha (PIK3CA) gene microsatellites and their link with breast cancer
      risk. In the present study, we investigate the guanine-thymine (GT) dinucleotide
      repeat polymorphism in intron 1 of PIK3CA gene in a cohort of 200 breast cancer
      patients and 200 healthy individuals and its link to the risk of developing
      breast cancer. The results of this study demonstrate that PIK3CA gene allele
      distribution in Isfahan population varies between 13 and 20 repeats. GT14 and
      GT16 were the most common allele present in patients, and GT17 was the most
      common allele in controls. Women with one or two alleles shorter than 17 GT
      repeat have a significantly higher risk of developing breast cancer [Odds ratio
      (OR) 3.6, p = 0.00001 and OR 3.98, p = 0.000001, respectively], in contrast,
      women with one or two alleles longer than 16 are at lower risk of breast cancer.
      This result suggests a potential role for this microsatellite as a predictive
      marker of breast cancer risk in Iranian women.

PMID- 24920353
TI  - Pharmacokinetic study of rosuvastatin in males and females.
AB  - Rosuvastatin is used to treat dyslipidemia and is metabolized by CYP2C9 that
      shows variable metabolic activity in males and females. Pharmacokinetics (PK) of
      drugs varies in males and females that may result in altered drug response and
      therapeutic efficacy. In current study, PK of rosuvastatin has been evaluated in
      males and females. A single oral dose (40 mg rosuvastatin), open-label and non
      controlled PK study was arranged. A reversed phase HPLC method was applied for
      quantification of rosuvastatin in serum samples. PK parameters of rosuvastatin
      were compared in males and females by applying student t test at 95 % confidence
      interval. The C max, [Formula: see text]and [Formula: see text]of rosuvastatin
      was significantly higher (p < 0.05) in females compared with males. The Vd/F of
      rosuvastatin was insignificantly higher (p > 0.05) in males compared with females
      while CL/F was significantly (p < 0.05) faster in males when compared at 95 %
      confidence interval. Rosuvastatin plasma level was significantly high in females
      compared with males that may be a possible reason for higher incidence of cardiac
      myopathy and other side effects in females. The variation in PK of drugs in males
      and females may require dose adjustment for maximum therapeutic effectiveness and
      safety.

PMID- 24920354
TI  - Childhood Maltreatment and Educational Outcomes.
AB  - Children (0-18 years) with maltreatment histories are vulnerable to experiencing
      difficulties across multiple domains of functioning, including educational
      outcomes that encompass not only academic achievement but also mental well-being.
      The current literature review adopted Slade and Wissow's model to examine (1) the
      link between childhood maltreatment and academic achievement, (2) the link
      between childhood maltreatment and mental health outcomes (i.e., emotional and
      behavioral difficulties), and (3) the bidirectional relationship between
      childhood academic achievement and mental health. In addition, we reviewed
      variables that might influence or help explain the link between childhood
      maltreatment and educational outcomes, drawing on developmental perspectives and
      Bronfenbrenner's ecological model. Finally, whenever possible, we presented
      findings specific to maltreated children in out-of-home care to highlight the
      unique challenges experienced by this population. Results indicated that children
      with maltreatment histories often experience impairments in both their academic
      performance (e.g., special education, grade retention, lower grades) and mental
      well-being (e.g., anxiety, low mood, aggression, social skills deficits, poor
      interpersonal relationships). These impairments appeared to be particularly
      pronounced among maltreated children in out-of-home care. Findings, albeit
      sparse, also indicated that mental health difficulties are negatively associated
      with children's academic achievement and, similarly, that academic achievement
      deficits are linked with mental health problems. The link between childhood
      maltreatment and educational outcomes may be partly explained through the
      disruption of key developmental processes in children, such as attachment,
      emotion regulation, and sense of agency. As well, maltreatment characteristics
      and the functioning of various systems in which children are embedded (e.g.,
      family, school, child welfare) can serve to positively or negatively influence
      the educational outcomes of maltreated children. The theoretical, research, and
      applied implications stemming from the findings are considered. 

PMID- 24920355
TI  - Targeted small noncoding RNA-directed gene activation in human cells.
AB  - A growing body of evidence suggests that noncoding RNA (ncRNA) transcripts play a
      fundamental role in regulating gene expression via targeting epigenetic
      modifications to particular loci in the genome. Classical examples of such
      regulation are X-chromosome inactivation and genomic imprinting; however it is
      now clear that ncRNAs exert their influence over a wider array of genes
      throughout the metazoan genome. Accumulating evidence suggests that the ncRNAs
      act as guides for epigenetic silencing complexes to specific sites within the
      genome. Those ncRNAs involved in regulating the expression of particular protein
      coding genes offer panoply of targets that when suppressed can result in
      derepression or activation of the ncRNA-targeted locus. Recent work has
      determined the underlying mechanisms involved in ncRNA-targeted epigenetic
      regulation in a subset of genes. These findings have resulted in a paradigm shift
      whereby targeted gene activation can be achieved, by targeting endogenous
      regulatory ncRNAs, producing potential novel treatments for genetic and
      infectious diseases where increases in gene expression are required. 

PMID- 24920356
TI  - Isolation of chromatoid bodies from mouse testis as a rich source of short RNAs.
AB  - RNA-protein (RNP) complexes and granules are powerful composites of merged
      functions and unique properties. The importance of RNPs in carrying out complex
      tasks in RNA processing and regulation is being increasingly revealed. One of the
      biggest RNP granules is the chromatoid body (CB) that is believed to orchestrate
      the RNA posttranscriptional regulation in haploid male germ cells. Here, we
      describe the CB isolation procedure, from mouse testis. After cross-linking and
      lysing the cells, the CBs are enriched by slow-speed centrifugation and
      immunoprecipitated using anti-MVH/DDX4 antibody. The method yields pure fractions
      of CBs, and it is robust, reproducible and does not require special equipment or
      abundant starting material. The CB is packed with large amounts of RNA,
      especially small RNAs. Isolation of the CBs provides a tool to enrich these RNA
      species. 

PMID- 24920357
TI  - Generation of endo-siRNAs in Xenopus laevis oocytes.
AB  - Endogenous siRNAs (endo-siRNAs) are well documented and characterized in C.
      elegans and Drosophila. Endo-siRNAs can also be found in vertebrates; however,
      their biology is much less clear. They are thought to be produced by Dicer and to
      contribute to transposon silencing. Because of their generally low abundance and
      their similarity with miRNAs and products of physiological RNA turn-over, endo
      siRNAs are difficult to investigate. Here, we report a system, oocytes from
      Xenopus laevis, that allows for the generation and analysis of endo-siRNAs from
      double-stranded RNA precursors. 

PMID- 24920358
TI  - Analysis of endo-siRNAs in Drosophila.
AB  - The small RNA silencing system is an important player in the control of gene
      expression. In particular analysis of the highly complex sequence repertoire of
      piRNAs and endogenous siRNAs directed against repetitive elements and transposons
      has been facilitated by the advent of next-generation sequencing tools. We are
      providing a detailed protocol for the creation of deep sequencing libraries in
      combination with a chemical modification step (periodate oxidation and beta
      elimination) that enriches for 3'-terminal modified small RNAs. This step can
      thus facilitate the detection and-since incorporation of the small RNA into the
      effector complex precedes the terminal methylation-determine the Argonaute
      loading state of certain small RNA species. Both, the oxidation as well as the
      deep sequencing library preparation are adaptations of popular, previously
      published protocols. The sequencing libraries described here can be sequenced on
      all flow cell types (i.e., single-end and paired-end) of the Illumina sequencing
      systems and are compatible with Illumina index reads. It is therefore also
      possible to analyze the libraries on the MiSeq system, for which currently only
      paired-end flow cells are available, and combine several libraries in multiplexed
      experiments. The chapter concludes with considerations concerning quality control
      and data analysis. 

PMID- 24920359
TI  - Methods for studying the biological consequences of endo-siRNA deficiency in
      Drosophila melanogaster.
AB  - Endogenous small interfering RNAs (endo-siRNAs) are a newly emerged class of
      small regulatory RNAs. In Drosophila melanogaster, the production of endo-siRNAs
      depends on the RNase III enzyme Dicer-2 (Dcr-2). Loss of dcr-2 function reduces
      the resistance of adult flies to various stresses and shortens their life span.
      The mutants also exhibit alterations in carbohydrate and lipid metabolism. These
      findings suggest that the endo-siRNA pathway plays a protective role during
      exposure to stress and aging in D. melanogaster, possibly by regulating metabolic
      homeostasis. Here, we describe the methods that were used to discover the
      phenotypes associated with endo-siRNA deficiency by using dcr-2 null mutants. 

PMID- 24920360
TI  - Small RNA library cloning procedure for deep sequencing of specific endogenous
      siRNA classes in Caenorhabditis elegans.
AB  - In recent years, distinct classes of small RNAs ranging in size from ~21 to 26
      nucleotides have been discovered and shown to play important roles in a wide
      array of cellular functions. Because of the abundance of these small RNAs,
      library preparation from an RNA sample followed by deep sequencing provides the
      identity and quantity of a particular class of small RNAs. In this chapter we
      describe a detailed protocol for preparing small RNA libraries for deep
      sequencing on the Illumina platform from the nematode C. elegans. 

PMID- 24920361
TI  - Assays for direct and indirect effects of C. elegans endo-siRNAs.
AB  - Ever since the discovery of the first microRNAs in C. elegans, increasing numbers
      of endogenous small RNAs have been discovered. Endogenous siRNAs (endo-siRNAs)
      have emerged in the last few years as a largely independent class of small RNAs
      that regulate endogenous gene expression, with mechanisms distinct from those of
      piRNAs and miRNAs. Quantification of these small RNAs and their effect on target
      RNAs is a powerful tool for the analysis of RNAi; however, detection of small
      RNAs can be difficult due to their small size and relatively low abundance. Here,
      we describe the novel FirePlex assay for directly detecting endo-siRNA levels in
      bulk, as well as an optimized qPCR method for detecting the effect of endo-siRNAs
      on gene targets. Intriguingly, the loss of endo-siRNAs frequently results in
      enhanced experimental RNAi. Thus, we also present an optimized method to assess
      the indirect impact of endo-siRNAs on experimental RNAi efficiency. 

PMID- 24920362
TI  - Extraction and nonradioactive detection of small RNA molecules.
AB  - The emergence of small RNAs as key and potent regulators of gene expression has
      prompted the need for robust detection and assay protocols to be developed for
      investigating their generation and tissue distribution. The physicochemical
      nature of these RNAs allows traditional assay methods to be employed; however,
      due to the relatively small size of endo-siRNAs, key changes to these protocols
      are required. Here, we present a method for the nonradioactive detection of endo
      siRNAs in mouse tissue and microinjected Xenopus oocytes. The method comprises
      steps for RNA extraction, PAGE, and low-stringency northern blotting using DIG
      labelled RNA probes. Moreover, it includes a strategy to design and generate
      cheap hybridization probes with greatly increased sensitivity. These methods may
      be used as a simple and robust protocol for nonradioactive detection of small
      RNAs or be combined with other strategies to potentially enhance signal
      intensity. 

PMID- 24920363
TI  - p19-mediated enrichment and detection of siRNAs.
AB  - p19 is an RNA binding protein originally isolated from the Carnation Italian ring
      spot virus (CIRV). It has been shown that p19 is a plant RNA-silencing suppressor
      that binds small interfering RNA (siRNA) with high affinity. A bifunctional p19
      fusion protein, with an N-terminal maltose binding protein (MBP) and a C-terminal
      chitin binding domain (CBD) allows protein purification and binding of p19 to
      chitin magnetic beads via the chitin binding domain. The fusion p19 protein
      recognizes and binds double-stranded RNAs (dsRNA) in the size range of 20-23
      nucleotides, but does not bind single strand RNA (ssRNA) or dsDNA. Furthermore,
      p19 can also bind mRNA, if there is a 19 bp blunt RNA duplex at the exact end of
      the RNA. Binding specificity of the p19 fusion protein for small dsRNA allows for
      detection of siRNAs derived either from exogenous or endogenous long dsRNA or
      microRNAs when hybridized to a complementary RNA. Here we describe a robust
      method using p19 and radioactive RNA probes to detect siRNAs in the sub-femtomole
      range and in the presence of a million-fold excess of total RNA. Unlike most
      nucleic acid detection methods, p19 selects for RNA hybrids of correct length and
      structure. This chapter describes the potential of p19 fusion protein to detect
      miRNAs, isolate exogenous or endogenous siRNAs, and purify longer RNAs that
      contain a 19-bp terminal RNA duplex. 

PMID- 24920364
TI  - Detection of small noncoding RNAs by in situ hybridization using probes of 2'-O
      methyl RNA + LNA.
AB  - In situ hybridization is a powerful method to provide information about
      contextual distribution and cellular origin of nucleic acids, e.g., in formalin
      fixed paraffin-embedded (FFPE) samples of tissue. Particularly the recently
      discovered classes of noncoding RNA (ncRNA) including endo-siRNAs and microRNAs
      require such a technique to enable their study and visualization in natural
      contexts, and in the last decade, many advances have been made, increasing our
      ability to specifically detect small ncRNAs. One of the key developments has been
      the demonstration of the superiority of using locked nucleic acid (LNA)-modified
      DNA probes for the detection of ncRNA in tissue. Here, we describe an alternative
      in situ hybridization protocol employing oligonucleotide probes consisting of
      combinations of LNA and 2'-O-methyl RNAs that under optimized hybridization
      buffer conditions can provide a highly sensitive assay performance with only 1 h
      hybridization time. 

PMID- 24920365
TI  - Enhanced detection of small RNAs using a nonradioactive approach.
AB  - Recent advancements in high-throughput sequencing have led to the identification
      of many new classes of small noncoding RNAs such as endo-siRNAs. Unfortunately,
      reliable quantification of RNAs by sequencing is difficult due to artifacts
      arising from various factors involved in cDNA library preparation. Northern blot
      is one of the leading methods used to confirm the presence of a given RNA
      sequence because it can accurately quantify the cellular abundance, the size of
      the small RNA and reveal the presence of potential precursors and RNA isoforms.
      Here, we present a comprehensive description of LNA probe design along with a
      recently developed highly sensitive and cost-effective nonradioactive northern
      blot approach termed LED. LED combines a cross-linking method (EDC) and
      digoxigenin (DIG) labeling, and it can detect small RNAs with concentrations as
      low as 0.05 fmol and requires as little as a few seconds of membrane exposure for
      signal generation. 

PMID- 24920366
TI  - Computing siRNA and piRNA overlap signatures.
AB  - High-throughput sequencing approaches opened the possibility to precisely map
      full populations of small RNAs to the genomic loci from which they originate. A
      bioinformatic approach revealed a strong tendency of sense and antisense piRNAs
      to overlap with each other over ten nucleotides and had a major role in
      understanding the mechanisms of piRNA biogenesis. Using similar approaches, it is
      possible to detect a tendency of sense and antisense siRNAs to overlap over 19
      nucleotides. Thus, the so-called overlap signature which describes the tendency
      of small RNA to map in a specific way relative to each other has become the
      approach of choice to identify and characterize specific classes of small RNAs.
      Although simple in essence, the bioinformatic methods used for this approach are
      not easily accessible to biologists. Here we provide a python software that can
      be run on most of desktop or laptop computers to compute small RNA signatures
      from files of sequencing read alignments. Moreover, we describe and illustrate
      step by step two different algorithms at the core of the software and which were
      previously used in a number of works. 

PMID- 24920367
TI  - Isolation of small interfering RNAs using viral suppressors of RNA interference.
AB  - The tombusvirus P19 VSR (viral suppressor of RNA interference) binds siRNAs with
      high affinity, whereas the Flockhouse Virus (FHV) B2 VSR binds both long double
      stranded RNA (dsRNA) and small interfering RNAs (siRNAs). Both VSRs are small
      proteins and function in plant and animal cells. Fusing a Nuclear Localization
      Signal (NLS) to the N-terminus shifts the localization of the VSR from
      cytoplasmic to nuclear, allowing researchers to specifically probe the
      subcellular distribution of siRNAs, and to investigate the function of nuclear
      and cytoplasmic siRNAs. This chapter provides a detailed protocol for the
      immunoprecipitation of siRNAs bound to epitope-tagged VSR and subsequent analysis
      by 3'-end-labeling using cytidine-3',5'-bis phosphate ([5'-(32)P]pCp) and
      northern blotting. 

PMID- 24920368
TI  - Computational analysis, biochemical purification, and detection of tRNA-derived
      small RNA fragments.
AB  - The rapidly growing list of small RNA species generated by next-generation
      sequencing technologies has accelerated the development of new bioinformatics
      tools for their detection. Small RNAs generated from tRNAs, transfer RNA-derived
      fragments (tRFs), represent a novel challenge in accurately identifying and
      distinguishing them from random degradation products of tRNAs. Here, we describe
      a bioinformatics approach to detect tRFs in next-generation sequencing libraries.
      We also present a biochemical purification protocol for enriching 5' tRFs and
      separating them from miRNAs. And finally, we suggest reliable methods for
      detecting and quantifying tRFs. 

PMID- 24920369
TI  - Differential DNA methylation patterns in endo-siRNAs mediated silencing of LINE-1
      retrotransposons.
AB  - Analyzing differences in DNA methylation is a powerful tool for assessing the
      effect of endo-siRNAs expression in the human genome. Here, we present a simple
      genome-wide DNA methylation assay that allows for a precise quantitative analysis
      of differences in the promoter of human long interspersed nuclear element 1 (LINE
      1 or L1) retrotransposons in response to endogenous and exogenous expression of
      endo-siRNAs. Using the DNA bisulfite modification sequencing, we have optimized
      the method to detect small changes in heterogeneously methylated L1 repeats at
      multiple regions across the genome. We also provide guidance for analysis of
      primary bisulfite sequencing data and interpretation of the methylation status
      using the Web-based bisulfite sequencing DNA methylation (BISMA) analysis. This
      refined and reproducible assay can be performed even using a small amount of
      genomic DNA and is suitable for the analysis of clinical tissue samples. 

PMID- 24920370
TI  - Applied neuroanatomy elective to reinforce and promote engagement with
      neurosensory pathways using interactive and artistic activities.
AB  - One in six Americans is currently affected by neurologic disease. As the United
      States population ages, the number of neurologic complaints is expected to
      increase. Thus, there is a pressing need for more neurologists as well as more
      neurology training in other specialties. Often interest in neurology begins
      during medical school, so improving education in medical neural courses is a
      critical step toward producing more neurologists and better neurology training in
      other specialists. To this end, a novel applied neuroanatomy elective was
      designed at the University of Texas Health Science Center at San Antonio
      (UTHSCSA) to complement the traditional first-year medical neuroscience course
      and promote engagement and deep learning of the material with a focus on
      neurosensory pathways. The elective covered four neurosensory modalities
      (proprioception/balance, vision, auditory, and taste/olfaction) over four
      sessions, each with a short classroom component and a much longer activity
      component. At each session, students reviewed the neurosensory pathways through
      structured presentations and then applied them to preplanned interactive
      activities, many of which allowed students to utilize their artistic talents.
      Students were required to complete subjective pre-course and post-course surveys
      and reflections. The survey results and positive student comments suggest that
      the elective was a valuable tool when used in parallel with the traditional
      medical neuroscience course in promoting engagement and reinforcement of the
      neurosensory material.

PMID- 24920371
TI  - Synthesis of bioactive beta-TCP coatings with tailored physico-chemical
      properties on zirconia bioceramics.
AB  - The objective of this work was to develop a synthesis procedure for the
      deposition of beta-TCP coatings with tailored physico-chemical properties on
      zirconia bioceramics. The synthesis procedure involved two steps: (i) a rapid wet
      chemical deposition of a biomimetic CaP coating and (ii) a subsequent post
      deposition processing of the biomimetic CaP coating, which included a heat
      treatment between 800 and 1200  degrees C, followed by a short sonication in a
      water bath. By regulating the heating temperature the topography of the beta-TCP
      coatings could be controlled. The average surface roughness (Ra) ranged from 42
      nm for the coating that was heated at 900  degrees C (TCP-900) to 630 nm for the
      TCP-1200 coating. Moreover, the heating temperature also affected the dissolution
      rate of the coatings in a physiological solution, their protein-adsorption
      capacity and their bioactivity in a simulated body fluid.

PMID- 24920372
TI  - The phenotypic and genetic structure of depression and anxiety disorder symptoms
      in childhood, adolescence, and young adulthood.
AB  - IMPORTANCE: The DSM-5 classifies mood and anxiety disorders as separate
      conditions. However, some studies in adults find a unidimensional internalizing
      factor that underpins anxiety and depression, while others support a
      bidimensional model where symptoms segregate into distress (depression and
      generalized anxiety) and fear factors (phobia subscales). However, little is
      known about the phenotypic and genetic structure of internalizing psychopathology
      in children and adolescents. OBJECTIVE: To investigate the phenotypic
      associations between depression and anxiety disorder symptom subscales and to
      test the genetic structures underlying these symptoms (DSM-5-related,
      unidimensional and bidimensional) across 3 developmental stages: childhood,
      adolescence, and early adulthood. DESIGN, SETTING, AND PARTICIPANTS: Two
      population-based prospective longitudinal twin/sibling studies conducted in the
      United Kingdom. The child sample included 578 twins (mean age, approximately 8
      and 10 years at waves 1 and 2, respectively). The adolescent and early adulthood
      sample included 2619 twins/siblings at 3 waves (mean age, 15, 17, and 20 years at
      each wave). MAIN OUTCOMES AND MEASURES: Self-report symptoms of depression and
      anxiety disorders. RESULTS: Phenotypically, when controlling for other anxiety
      subscales, depression symptoms were only associated with generalized anxiety
      disorder symptoms in childhood (r = 0.20-0.21); this association broadened to
      panic and social phobia symptoms in adolescence (r = 0.17-0.24 and r = 0.14-0.16,
      respectively) and all anxiety subscales in young adulthood (r = 0.06-0.19). The
      genetic associations were in line with phenotypic results. In childhood, anxiety
      subscales were influenced by a single genetic factor that did not contribute to
      genetic variance in depression symptoms, suggesting largely independent genetic
      influences on anxiety and depression. In adolescence, genetic influences were
      significantly shared between depression and all anxiety subscales in agreement
      with DSM-5 conceptualization. In young adulthood, a genetic internalizing factor
      influencing depression and all anxiety subscales emerged, alongside a small
      significant genetic fear factor. CONCLUSIONS AND RELEVANCE: These results provide
      preliminary evidence for different phenotypic and genetic structures of
      internalizing disorder symptoms in childhood, adolescence, and young adulthood,
      with depression and anxiety becoming more associated from adolescence. The
      results inform molecular genetics research and transdiagnostic treatment
      approaches. The findings affirm the need to continue examining the classification
      of mood and anxiety disorders in diagnostic systems.

PMID- 24920375
TI  - Do individually ventilated cage systems generate a problem for genetic mouse
      model research?
AB  - Technological developments over recent decades have produced a novel housing
      system for laboratory mice, so-called 'individually ventilated cage' (IVC)
      systems. IVCs present a cage environment which is different to conventional
      filter-top cages (FILTER). Nothing is known about the consequences of IVC housing
      on genetic mouse models, despite studies reporting IVC-mediated changes to the
      phenotypes of inbred mouse strains. Thus, in this study, we systematically
      compared the established behavioural phenotype of a validated mouse model for the
      schizophrenia risk gene neuregulin 1 (TM Nrg1 HET) kept in FILTER housing with
      Nrg1 mutant mice raised in IVC systems. We found that particular schizophrenia
      relevant endophenotypes of TM Nrg1 HETs which had been established and widely
      published using FILTER housing were altered when mice were raised in IVC housing.
      IVCs diminished the schizophrenia-relevant prepulse inhibition deficit of Nrg1
      mutant males. Furthermore, IVC housing had a sex-dependent moderate effect on the
      locomotive phenotype of Nrg1 mice across test paradigms. Behavioural effects of
      IVC housing were less prominent in female mice. Thus, transferring the breeding
      colony of mouse mutants from FILTER to IVC systems can shift disease-relevant
      behaviours and therefore challenge the face validity of these mice. Researchers
      facing an upgrade of their mouse breeding or holding facilities to IVC systems
      must be aware of the potential impact this upgrade might have on their genetic
      mouse models. Future publications should provide more details on the cage system
      used to allow appropriate data comparison across research sites. 

PMID- 24920376
TI  - Prescriber response to unsolicited prescription drug monitoring program reports
      in Massachusetts.
AB  - PURPOSE: To describe prescriber response to unsolicited patient reports from the
      Massachusetts prescription drug monitoring program (PDMP). METHODS: Prescribers
      were surveyed upon receipt of unsolicited reports of their patients' prescription
      history and three months later. We assessed prescribers' awareness of other
      prescribers listed in the report, their clinical assessment of medical necessity
      of all prescribed medications, actions taken by prescribers after receiving the
      report, and usefulness of the report. RESULTS: Of the 333 respondents to the
      initial survey, only 28 (8.4%) were aware of most, all, or nearly all other
      prescribers. A total of 146 (43.8%) reported having sufficient knowledge to
      determine whether the prescriptions were medically necessary, of whom 102 (69.6%)
      felt the prescriptions were unwarranted. Of the 163 respondents to the follow-up
      survey, 31.3% added the report to the patient's file, 22.7% discussed the report
      with other prescribers on the report, 21.5% took no action, and 6% discussed the
      report with the patient (representing two-thirds of respondents who saw the
      patient after receiving the report). Most respondents felt that the report was
      useful for their practice and easy to understand. CONCLUSIONS: Unsolicited
      reporting of PDMP data has the potential to improve clinical practice by alerting
      providers about patients with multiple prescribers and potentially medically
      unnecessary prescriptions.

PMID- 24920373
TI  - The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase
      activity, Ca(2+) and Mg(2+) dependent-DNase activity and antifungal action on
      Moniliophthora perniciosa.
AB  - BACKGROUND: The production and accumulation of pathogenesis-related proteins (PR
      proteins) in plants in response to biotic or abiotic stresses is well known and
      is considered as a crucial mechanism for plant defense. A pathogenesis-related
      protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction
      cDNA library and named TcPR-4b. RESULTS: TcPR-4b presents a Barwin domain with
      six conserved cysteine residues, but lacks the chitin-binding site. Molecular
      modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain
      the protein structure, and of several conserved amino acids for the catalytic
      activity. In the cacao genome, TcPR-4b belonged to a small multigene family
      organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and
      susceptible cacao plants infected by M. perniciosa showed an increase of
      expression at 48 hours after infection (hai) in both cacao genotypes. After the
      initial stage (24-72 hai), the TcPR-4b expression was observed at all times in
      the resistant genotypes, while in the susceptible one the expression was
      concentrated at the final stages of infection (45-90 days after infection). The
      recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase
      activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal
      action against M. perniciosa, and the reduction of M. perniciosa survival was
      related to ROS production in fungal hyphae. CONCLUSION: To our knowledge, this is
      the first report of a PR-4 showing simultaneously RNase, DNase and antifungal
      properties, but no chitinase activity. Moreover, we showed that the antifungal
      activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b
      nuclease activities may be related to the establishment and maintenance of
      resistance, and to the PCD mechanism, in resistant and susceptible cacao
      genotypes, respectively.

PMID- 24920377
TI  - Abnormalities of mental rotation of hands associated with speed of information
      processing and executive function in chronic schizophrenic patients.
AB  - AIM: Deficits in mental imagery ability have been reported in patients with
      schizophrenia. However, there is scarce evidence about the correlation between
      impairment in mental rotation and other cognitive deficits in the patients. The
      aim of this study was to assess mental rotation ability, along with other
      measures of cognitive function in patients with schizophrenia. METHODS: The
      performance of 29 patients with schizophrenia was compared with 29 healthy
      controls. Mental rotation was measured with the Hand Rotation Task, and cognitive
      functions were measured with the Brief Assessment of Cognition in Schizophrenia
      (BACS). RESULTS: On Hand Rotation Task, the patients were significantly slower
      and less accurate compared to controls. Moreover, mental rotation accuracy was
      significantly correlated with all the BACS domains except verbal memory. In
      multiple regression analysis, the two BACS subscales, Tower of London and Symbol
      Coding tasks, were significant predictors and accounted for 41% of the variance
      in accuracy in the patients. CONCLUSION: These results support previous findings
      showing dysfunction of the posterior parietal cortex in schizophrenia, which is
      involved in general mental rotation, as well as other cognitive processes.

PMID- 24920378
TI  - Development of a Japanese version of the reported and intended behaviour scale:
      reliability and validity.
AB  - AIM: The Reported and Intended Behaviour Scale (RIBS) was developed in the U.K.
      to measure mental health-related behavior. The current study aimed to evaluate
      the applicability, and reliability of a Japanese version of the RIBS (RIBS-J) in
      a Japanese context, and further examine the construct validity of the RIBS-J.
      METHODS: The sample included 224 undergraduate and postgraduate students at a
      Japanese university. Cronbach's alpha was used to assess internal consistency.
      Pearson's correlation coefficient was used to examine the divergent validity
      between the RIBS-J and the Mental Health Knowledge Schedule and the convergent
      validity between the second subscale of the RIBS-J and Japanese version of the
      Social Distance Scale. Confirmatory factor analysis assessed the goodness of
      model fit of the RIBS-J. We also examined test-retest reliability with another
      undergraduate sample (n = 29). RESULTS: Most items exhibited no floor/ceiling
      effect. High internal consistency (alpha = 0.83) was reported. The second
      subscale of the RIBS-J, measuring intended behavior, correlated with the Mental
      Health Knowledge Schedule (r = 0.33, P < 0.001) and the Japanese version of the
      Social Distance Scale (r = -0.60, P < 0.001). In addition, confirmatory factor
      analysis found good model fit for the RIBS-J (chi2  = 41.001, d.f. = 19, P =
      0.002, goodness-of-fit index = 0.956, adjusted goodness-of-fit index = 0.916,
      comparative fit index = 0.955, root mean square error of approximation = 0.072).
      Overall test-retest reliability (rhoc) was 0.71. CONCLUSION: The RIBS-J is an
      appropriate and psychometrically robust measure of behavior towards individuals
      with mental health problems in Japan. Further studies using a community sample
      could assess the generalizability of our findings.

PMID- 24920379
TI  - Neural responses to various rewards and feedback in the brains of adolescent
      Internet addicts detected by functional magnetic resonance imaging.
AB  - AIM: This study aimed to examine differences in brain activation for various
      types of reward and feedback in adolescent Internet addicts (AIA) and normal
      adolescents (NA) using functional magnetic resonance imaging (fMRI). METHODS: AIA
      (n = 15) and NA (n = 15) underwent fMRI while performing easy tasks for which
      performance feedback (PF), social reward (SR) (such as compliments), or monetary
      reward (MR) was given. Using the no reward (NR) condition, three types of
      contrasts (PF-NR, SR-NR, and MR-NR) were analyzed. RESULTS: In NA, we observed
      activation in the reward-related subcortical system, self-related brain region,
      and other brain areas for the three contrasts, but these brain areas showed
      almost no activation in AIA. Instead, AIA showed significant activation in the
      dorsolateral prefrontal cortex for the PF-NR contrast and the negative
      correlation was found between the level of activation in the left superior
      temporal gyrus (BA 22) and the duration of Internet game use per day in AIA.
      CONCLUSION: These findings suggest that AIA show reduced levels of self-related
      brain activation and decreased reward sensitivity irrespective of the type of
      reward and feedback. AIA may be only sensitive to error monitoring regardless of
      positive feelings, such as sense of satisfaction or achievement.

PMID- 24920380
TI  - Clinical characteristics and diagnostic confirmation of Internet addiction in
      secondary school students in Wuhan, China.
AB  - AIM: This study investigated the clinical characteristics of internet addiction
      using a cross-sectional survey and psychiatric interview. METHODS: A structured
      questionnaire consisted of demographics, Symptom Checklist 90, Self-Rating
      Anxiety Scale, Self-Rating Depression Scale, and Young's Internet Addiction Test
      (YIAT) was administered to students of two secondary schools in Wuhan, China.
      Students with a score of 5 or higher on the YIAT were classified as having
      Internet Addiction Disorder (IAD). Two psychiatrists interviewed students with
      IAD to confirm the diagnosis and evaluate their clinical characteristics.
      RESULTS: Of a total of 1076 respondents (mean age 15.4 +/- 1.7 years; 54.1%
      boys), 12.6% (n = 136) met the YIAT criteria for IAD. Clinical interviews
      ascertained the Internet addiction of 136 pupils and also identified 20 students
      (14.7% of IAD group) with comorbid psychiatric disorders. Results from
      multinomial logistic regression indicated that being male, in grade 7-9, poor
      relationship between parents and higher self-reported depression scores were
      significantly associated with the diagnosis of IAD. CONCLUSION: These results
      advance our understanding of the clinical characteristics of Internet addiction
      in Chinese secondary school students and may help clinicians, teachers, and other
      stakeholders better manage this increasingly serious mental condition.

PMID- 24920381
TI  - SAR studies on curcumin's pro-inflammatory targets: discovery of prenylated
      pyrazolocurcuminoids as potent and selective novel inhibitors of 5-lipoxygenase.
AB  - The anticarcinogenic and anti-inflammatory properties of curcumin have been
      extensively investigated, identifying prostaglandin E2 synthase (mPGES)-1 and 5
      lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high
      affinity targets. A comparative structure-activity study revealed three
      modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the
      acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii)
      hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The
      prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming
      curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis
      along with reduced 5-LO product levels. Other pro-inflammatory targets of
      curcumin (i.e., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-kappaB,
      nuclear factor-erythroid 2-related factor-2, and signal transducer and activator
      of transcription 3) were hardly affected by 11. The strict structural
      requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific
      interactions rather than redox or membrane effects underlie the inhibition of
      mPGES-1 and 5-LO by curcumin.

PMID- 24920382
TI  - Using historical biogeography to test for community saturation.
AB  - Saturation is the idea that a community is effectively filled with species, such
      that no more can be added without extinctions. This concept has important
      implications for many areas of ecology, such as species richness, community
      assembly, invasive species and climate change. Here, we illustrate how
      biogeography can be used to test for community saturation, when combined with
      data on local species richness, phylogeny and climate. We focus on a clade of
      frogs (Terrarana) and the impact of the Great American Biotic Interchange on
      patterns of local richness in Lower Middle America and adjacent regions. We
      analyse data on species richness at 83 sites and a time-calibrated phylogeny for
      363 species. We find no evidence for saturation, and show instead that biotic
      interchange dramatically increased local richness in the region. We suggest that
      historical biogeography offers thousands of similar long-term natural experiments
      that can be used to test for saturation. 

PMID- 24920383
TI  - Riboadenosine-substituted DNA probes for self-illuminating real-time monitoring
      of exonuclease III activity and exonuclease III-assisted target recycling.
AB  - We develop a riboadenosine-substituted DNA probe-based bioluminescence method for
      real-time monitoring of exonuclease III (Exo III) activity and Exo III-assisted
      target recycling. This method employs the target-dependent ATP as the
      bioluminescence reporter without the involvement of any sophisticated luciferase
      manipulations, and the glow-type reaction kinetics facilitates the performance of
      imaging assay. 

PMID- 24920384
TI  - Functional analysis of limb transcriptional enhancers in the mouse.
AB  - Transcriptional enhancers are genomic sequences bound by transcription factors
      that act together with basal transcriptional machinery to regulate gene
      transcription. Several high-throughput methods have generated large datasets of
      tissue-specific enhancer sequences with putative roles in developmental
      processes. However, few enhancers have been deleted from the genome to determine
      their roles in development. To understand the roles of two enhancers active in
      the mouse embryonic limb bud we deleted them from the genome. Although the genes
      regulated by these enhancers are unknown, they were selected because they were
      identified in a screen for putative limb bud-specific enhancers associated with
      p300, an acetyltransferase that participates in protein complexes that promote
      active transcription, and because the orthologous human enhancers (H1442 and
      H280) drive distinct lacZ expression patterns in limb buds of embryonic day (E)
      11.5 transgenic mice. We show that the orthologous mouse sequences, M1442 and
      M280, regulate dynamic expression in the developing limb. Although significant
      transcriptional differences in enhancer-proximal genes in embryonic limb buds
      accompany the deletion of M1442 and M280 no gross limb malformations during
      embryonic development were observed, demonstrating that M1442 and M280 are not
      required for mouse limb development. However, M280 is required for the
      development and/or maintenance of body size; M280 mice are significantly smaller
      than controls. M280 also harbors an "ultraconserved" sequence that is identical
      between human, rat, and mouse. This is the first report of a phenotype resulting
      from the deletion of an ultraconserved element. These studies highlight the
      importance of determining enhancer regulatory function by experiments that
      manipulate them in situ and suggest that some of an enhancer's regulatory
      capacities may be developmentally tolerated rather than developmentally required.

PMID- 24920387
TI  - Selective fishing induces density-dependent growth.
AB  - Over the last decades, views on fisheries management have oscillated between
      alarm and trust in management progress. The predominant policy for remedying the
      world fishing crisis aims at maximum sustainable yield (MSY) by adjusting gear
      selectivity and fishing effort. Here we report a case study on how striving for
      higher yields from the Eastern Baltic cod stock by increasing selectivity has
      become exceedingly detrimental for its productivity. Although there is a
      successive increase in numbers of undersized fish, growth potential is severely
      reduced, and fishing mortality in fishable size has increased. Once density
      dependent growth is introduced, the process is self-enforcing as long as the
      recruitment remains stable. Our findings suggest that policies focusing on
      maximum yield while targeting greater sizes are risky and should instead
      prioritize catch rates over yield. Disregarding the underlying population
      structure may jeopardize stock productivity, with dire consequences for the
      fishing industry and ecosystem structure and function. 

PMID- 24920388
TI  - Phase-specific Raman spectroscopy for fast segmented microfluidic flows.
AB  - An intensifier based Raman measuring strategy is introduced which allows for a
      phase-specific signal detection of one single phase in segmented flows at droplet
      generation frequencies of potentially up to several kHz. 

PMID- 24920389
TI  - Hearing characteristics of cephalopods: modeling and environmental impact study.
AB  - Cephalopods (octopus, squid and cuttlefish) are some of the most intriguing
      molluscs, and they represent economically important commercial marine species for
      fisheries. Previous studies have shown that cephalopods are sensitive to
      underwater particle motion, especially at low frequencies in the order of 10 Hz.
      The present paper deals with quantitative modeling of the statocyst system in
      three cephalopod species: Octopus vulgaris, Sepia officinalis and Loligo
      vulgaris. The octopus's macula/statolith organ was modeled as a 2nd-order dynamic
      oscillator using parameter values estimated from scanning electron micrograph
      images. The modeling results agree reasonably well with experimental data
      (acceleration threshold) in the three cephalopod species. Insights made from
      quantitative modeling and simulating the particle motion sensing mechanism of
      cephalopods elucidated their underwater particle motion detection capabilities.
      Sensitivity to emerging environmental issues, such as low frequency noise caused
      by near-shore wind farms and increasing levels of carbon dioxide in the ocean,
      and sensitivity to sounds produced by impending landslides were investigated in
      octopus using the model. 

PMID- 24920390
TI  - Hidden synaptic differences in a neural circuit underlie differential behavioral
      susceptibility to a neural injury.
AB  - Individuals vary in their responses to stroke and trauma, hampering predictions
      of outcomes. One reason might be that neural circuits contain hidden variability
      that becomes relevant only when those individuals are challenged by injury. We
      found that in the mollusc, Tritonia diomedea, subtle differences between animals
      within the neural circuit underlying swimming behavior had no behavioral
      relevance under normal conditions but caused differential vulnerability of the
      behavior to a particular brain lesion. The extent of motor impairment correlated
      with the site of spike initiation in a specific neuron in the neural circuit,
      which was determined by the strength of an inhibitory synapse onto this neuron.
      Artificially increasing or decreasing this inhibitory synaptic conductance with
      dynamic clamp correspondingly altered the extent of motor impairment by the
      lesion without affecting normal operation. The results suggest that neural
      circuit differences could serve as hidden phenotypes for predicting the
      behavioral outcome of neural damage. 

PMID- 24920391
TI  - Three pools of plasma membrane cholesterol and their relation to cholesterol
      homeostasis.
AB  - When human fibroblasts take up plasma low density lipoprotein (LDL), its
      cholesterol is liberated in lysosomes and eventually reaches the endoplasmic
      reticulum (ER) where it inhibits cholesterol synthesis by blocking activation of
      SREBPs. This feedback protects against cholesterol overaccumulation in the plasma
      membrane (PM). But how does ER know whether PM is saturated with cholesterol? In
      this study, we define three pools of PM cholesterol: (1) a pool accessible to
      bind 125I-PFO*, a mutant form of bacterial Perfringolysin O, which binds
      cholesterol in membranes; (2) a sphingomyelin(SM)-sequestered pool that binds
      125I-PFO* only after SM is destroyed by sphingomyelinase; and (3) a residual pool
      that does not bind 125I-PFO* even after sphingomyelinase treatment. When LDL
      derived cholesterol leaves lysosomes, it expands PM's PFO-accessible pool and,
      after a short lag, it also increases the ER's PFO-accessible regulatory pool.
      This regulatory mechanism allows cells to ensure optimal cholesterol levels in PM
      while avoiding cholesterol overaccumulation.

PMID- 24920392
TI  - Localized increase of tissue oxygen tension by magnetic targeted drug delivery.
AB  - Hypoxia is the major hindrance to successful radiation therapy of tumors.
      Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more
      O2 have been clinically disappointing, largely due to the way O2 is transported
      and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic
      manipulation of O2 transport increases vascular resistance due to metabolic
      autoregulation of blood flow to prevent over oxygenation. This study investigates
      a new technology to increase O2 delivery to a target tissue by decreasing the Hb
      O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2
      affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases
      without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs),
      synthetized using gadolinium oxide, were coated with the cell permeable Hb
      allosteric effector L35 (3,5-trichlorophenylureido-phenoxy-methylpropionic acid).
      L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated
      PMNPs (L35-PMNPs) were intravenously infused (10 mg kg(-1)) to hamsters
      instrumented with the dorsal window chamber model. A magnetic field of 3 mT was
      applied to localize the effects of the L35-PMNPs to the window chamber. Systemic
      O2 transport characteristics and microvascular tissue oxygenation were measured
      after administration of L35-PMNPs with and without magnetic field. The tissue PO2
      in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field
      decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood
      flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with
      magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or
      microhemodynamic changes. These results indicate that localized modification of
      Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O2
      delivery or triggering O2 autoregulation mechanisms. This technology can be used
      to treat local hypoxia and to increase O2 in tumors, enhancing the efficacy of
      radiation therapies. 

PMID- 24920393
TI  - Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS
      CoV).
AB  - BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV)
      represents a current threat to the Arabian Peninsula, and potential pandemic
      disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and
      killed 282. We briefly summarize the state of the outbreak, and highlight
      unanswered questions and various explanations for the observed epidemiology.
      FINDINGS: The continuing but infrequent cases of MERS-CoV reported over the past
      two years have been puzzling and difficult to explain. The epidemiology of MERS
      CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained
      epidemic, suggests a low reproductive number. Furthermore, a clear source of
      infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has
      been present in Saudi Arabia over several mass gatherings, including the 2012 and
      2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an
      epidemic arising. CONCLUSIONS: The observed epidemiology of MERS-CoV is quite
      distinct and does not clearly fit either a sporadic or epidemic pattern. Possible
      explanations of the unusual features of the epidemiology of MERS-CoV include
      sporadic ongoing infections from a non-human source; human to human transmission
      with a large proportion of undetected cases; or a combination of both. The virus
      has been identified in camels; however the mode of transmission of the virus to
      humans remains unknown, and many cases have no history of animal contact. In
      order to gain a better understanding of the epidemiology of MERS CoV, further
      investigation is warranted.

PMID- 24920394
TI  - N-feruloylserotonin in preventive combination therapy with methotrexate reduced
      inflammation in adjuvant arthritis.
AB  - Many of disease-modifying anti-rheumatic drugs often have side effects at high
      doses and/or during long-term administration. Increased efficacy without
      increased toxicity is expected for combination therapy of rheumatoid arthritis
      (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f
      5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease
      progression and inflammation in arthritic rats. Adjuvant arthritis was induced by
      intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant
      in Lewis rats. The experiment included healthy animals, arthritic animals without
      any drug administration, arthritic animals with administration of N-f-5HT in the
      oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in
      the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with
      the combination of N-f-5HT and MTX. N-f-5HT in monotherapy reduced only
      activation of NF-kappaB and did not have any significant effect on other
      parameters monitored. Low-dose treatment of MTX decreased the level of IL-1beta
      and MCP-1 on day 14 and activation of NF-kappaB in liver without significant
      effect on other parameters. N-f-5HT and MTX combination showed both the anti
      arthritic (hind paw volume and arthritic score) and anti-inflammatory effect
      (plasmatic levels of IL-1beta, IL-17, MCP-1, CRP, and activation of NF-kappaB in
      liver). In combination with MTX, N-f-5HT markedly potentiated the therapeutic
      effect of MTX low dose, which resulted in significant improvement of all
      parameters measured. The findings showed that the combination therapy
      simultaneously decreased multiple markers of inflammation, a result crucial for
      future therapy of RA.

PMID- 24920395
TI  - Public perceptions of non-pharmaceutical interventions for reducing transmission
      of respiratory infection: systematic review and synthesis of qualitative studies.
AB  - BACKGROUND: Non-pharmaceutical public health interventions may provide simple,
      low-cost, effective ways of minimising the transmission and impact of acute
      respiratory infections in pandemic and non-pandemic contexts. Understanding what
      influences the uptake of non-pharmaceutical interventions such as hand and
      respiratory hygiene, mask wearing and social distancing could help to inform the
      development of effective public health advice messages. The aim of this synthesis
      was to explore public perceptions of non-pharmaceutical interventions that aim to
      reduce the transmission of acute respiratory infections. METHODS: Five online
      databases (MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science) were
      systematically searched. Reference lists of articles were also examined. We
      selected papers that used a qualitative research design to explore perceptions
      and beliefs about non-pharmaceutical interventions to reduce transmission of
      acute respiratory infections. We excluded papers that only explored how health
      professionals or children viewed non-pharmaceutical respiratory infection
      control. Three authors performed data extraction and assessment of study quality.
      Thematic analysis and components of meta-ethnography were adopted to synthesise
      findings. RESULTS: Seventeen articles from 16 studies in 9 countries were
      identified and reviewed. Seven key themes were identified: perceived benefits of
      non-pharmaceutical interventions, perceived disadvantages of non-pharmaceutical
      interventions, personal and cultural beliefs about infection transmission,
      diagnostic uncertainty in emerging respiratory infections, perceived
      vulnerability to infection, anxiety about emerging respiratory infections and
      communications about emerging respiratory infections. The synthesis showed that
      some aspects of non-pharmaceutical respiratory infection control (particularly
      hand and respiratory hygiene) were viewed as familiar and socially responsible
      actions to take. There was ambivalence about adopting isolation and personal
      distancing behaviours in some contexts due to their perceived adverse impact and
      potential to attract social stigma. Common perceived barriers included beliefs
      about infection transmission, personal vulnerability to respiratory infection and
      concerns about self-diagnosis in emerging respiratory infections. CONCLUSIONS:
      People actively evaluate non-pharmaceutical interventions in terms of their
      perceived necessity, efficacy, acceptability, and feasibility. To enhance uptake,
      it will be necessary to address key barriers, such as beliefs about infection
      transmission, rejection of personal risk of infection and concern about the
      potential costs and stigma associated with some interventions.

PMID- 24920396
TI  - Visceral leishmaniasis is associated with marked changes in serum lipid profile.
AB  - BACKGROUND: Infection is often accompanied by lipid profile alterations. The aim
      of this study was to evaluate the lipid profile changes in patients with visceral
      leishmaniasis (VL). MATERIALS AND METHODS: We included 15 patients [10 men, aged
      50 (24-82) years old] with VL and 15 age- and sex-matched controls. The
      parameters estimated at diagnosis and 4 months after VL resolution were total
      cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides
      (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoproteins (apo) A-Iota,
      B, E, C-II, C-III, lipoprotein (a) [Lp(a)], activities of lipoprotein-associated
      phospholipase A2 (Lp-PLA2), HDL-Lp-PLA2, PON1 (paraoxonase 1) and cholesterol
      ester transfer protein (CETP), cytokines (interleukins 1beta and 6 and tumour
      necrosis factor alpha), as well as LDL subfraction profile. RESULTS: Patients
      with VL at diagnosis had lower levels of TC, LDL-C, apoBeta and Lp(a), and higher
      TG and apoE concentrations compared with 4 months after VL resolution. The
      activities of Lp-PLA2, HDL-Lp-PLA2 and RhoOmicronNu1 were reduced at diagnosis
      compared with post-treatment values. VL patients had decreased levels of both
      large and sdLDL-C at diagnosis; no effect on mean LDL particle size was observed.
      Patients with VL at diagnosis had decreased HDL-C and apoA-I concentrations;
      these increased 4 months after VL resolution, but remained lower compared with
      controls. The activities of HDL-Lp-PLA2 and PON1 remained lower in patients after
      VL resolution compared with controls. CONCLUSIONS: Patients with VL exhibit
      increased TG levels and decreased cholesterol subclasses at diagnosis. HDL-C,
      apoA-I and associated enzymes remain lower 4 months after VL resolution compared
      with controls.

PMID- 24920397
TI  - Mosaic tetrasomy 13q and phylloid hypomelanosis: a case report and review of the
      literature.
AB  - A 6-year-old girl presented for evaluation of skin discoloration. Examination
      revealed oval and oblong hypopigmented macules on her trunk and extremities.
      Cytogenetic studies and immunohistochemistry of biopsies from normally pigmented
      and hypopigmented skin revealed mosaicism for partial tetrasomy for 13q with low
      melanocyte levels in lesional skin. The patient was diagnosed with phylloid
      hypomelanosis (PH), a distinct clinical entity linked to abnormalities in
      chromosome 13. This article reviews the literature regarding PH and supports the
      notion that mosaicism of the melanocyte region of chromosome 13q is responsible
      for PH. 

PMID- 24920398
TI  - The photo-Nazarov reaction: scope and application.
AB  - The reaction conditions and scope of the photo-Nazarov reaction of aryl vinyl
      ketones were investigated. In contrast to the conventional acid-catalyzed
      methods, this photolytic electrocyclization proceeds in the neutral or basic
      conditions. Irradiating substrates bearing various aromatic rings, acid-sensitive
      groups, cyclohexenyl, cycloheptenyl, and unsaturated pyran with UV-light (254 nm)
      smoothly yielded hexahydrofluorenones and related structures. This photo-Nazarov
      reaction could also be applicable to the substrates carrying beta-alkyl groups on
      the enone, which gave corresponding polycyclic rings containing quaternary
      centers. These photo-electrocyclized products may prove useful for synthesizing a
      variety of natural products and their derivatives. Further application of this
      mild photo-Nazarov reaction in the synthesis of taiwaniaquinol B was achieved. 

PMID- 24920399
TI  - Health policy update: rethinking hospital readmission as a surgical quality
      measure.

PMID- 24920400
TI  - Minorities, men, and unmarried amyotrophic lateral sclerosis patients are more
      likely to die in an acute care facility.
AB  - Studies suggest that dying at home is a more favorable experience. This study
      investigated where amyotrophic lateral sclerosis (ALS) patients die and the
      patient demographics associated with dying in an acute care facility or nursing
      home compared to home or hospice. Centers for Disease Control and Prevention
      Multiple Cause Mortality Files from 2005 to 2010 were used to identify ALS
      patients and to classify place of death. Multinomial logistic regression was used
      to determine the association between patient demographics and place of death.
      Between 2005 and 2010, 40,911 patients died of ALS in the United States. Place of
      death was as follows: home or hospice facility 20,231 (50%), acute care facility
      (25%), and nursing home (20%). African Americans (adjusted multinomial odds ratio
      (aMOR) 2.56, CI 2.32-2.83), Hispanics (aMOR 1.44, CI 1.30-1.62), and Asians (aMOR
      1.87, CI 1.57-2.22) were more likely to die in an acute care facility, whereas
      females (aMOR 0.76, CI 0.72-0.80) and married individuals were less likely.
      Hispanics (aMOR 0.68, CI 0.58-0.79) and married individuals were less likely to
      die in a nursing home. In conclusion, minorities, men, and unmarried individuals
      are more likely to die in an acute care facility. Further studies are needed to
      better understand place of death preferences.

PMID- 24920401
TI  - Negotiated control between the manual and visual systems for visually guided hand
      reaching movements.
AB  - BACKGROUND: Control of reaching movements for manual work, vehicle operation, or
      interactions with manual interfaces requires concurrent gaze control for visual
      guidance of the hand. We hypothesize that reaching movements are based on
      negotiated strategies to resolve possible conflicting demands placed on body
      segments shared by the visual (gaze) and manual (hand) control systems. Further,
      we hypothesize that a multiplicity of possible spatial configurations
      (redundancy) in a movement system enables a resolution of conflicting demands
      that does not require sacrificing the goals of the two systems. METHODS: The
      simultaneous control of manual reach and gaze during seated reaching movements
      was simulated by solving an inverse kinematics model wherein joint trajectories
      were estimated from a set of recorded hand and head movements. A secondary
      objective function, termed negotiation function, was introduced to describe a
      means for the manual reach and gaze directing systems to balance independent
      goals against (possibly competing) demands for shared resources, namely the torso
      movement. For both systems, the trade-off may be resolved without sacrificing
      goal achievement by taking advantage of redundant degrees of freedom. Estimated
      joint trajectories were then compared to joint movement recordings from ten
      participants. Joint angles were predicted with and without the negotiation
      function in place, and model accuracy was determined using the root-mean-square
      errors (RMSEs) and differences between estimated and recorded joint angles.
      RESULTS: The prediction accuracy was generally improved when negotiation was
      included: the negotiated control reduced RMSE by 16% and 30% on average when
      compared to the systems with only manual or visual control, respectively.
      Furthermore, the RMSE in the negotiated control system tended to improve with
      torso movement amplitude. CONCLUSIONS: The proposed model describes how multiple
      systems cooperate to perform goal-directed human movements when those movements
      draw upon shared resources. Allocation of shared resources can be undertaken by a
      negotiation process that is aware of redundancies and the existence of multiple
      solutions within the individual systems.

PMID- 24920404
TI  - Surgical treatment of carotid body tumour: a report of 39 cases and a new
      classification of carotid body tumour: our experience.

PMID- 24920405
TI  - Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by
      the combination of proteomics and chemical probe-based assay.
AB  - Cytochrome P450 (CYP) is one of the most important drug-metabolizing enzyme
      families, which participates in the biotransformation of many endogenous and
      exogenous compounds. Quantitative analysis of CYP expression levels is important
      when studying the efficacy of new drug molecules and assessing drug-drug
      interactions in drug development. At present, chemical probe-based assay is the
      most widely used approach for the evaluation of CYP activity although there are
      cross-reactions between the isoforms with high sequence homologies. Therefore,
      quantification of each isozyme is highly desired in regard to meeting the ever
      increasing requirements for carrying out pharmacokinetics and personalized
      medicine in the academic, pharmaceutical, and clinical setting. Herein, an
      absolute quantification method was employed for the analysis of the seven
      isoforms CYP1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1 using a proteome-derived
      approach in combination with stable isotope dilution assay. The average absolute
      amount measured from twelve human liver microsomes samples were 39.3, 4.3, 54.0,
      4.6, 10.3, 3.0, and 9.3 (pmol/mg protein) for 1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and
      2E1, respectively. Importantly, the expression level of CYP3A4 showed high
      correlation (r = 0.943, p < 0.0001) with the functional activity, which was
      measured using bufalin-a highly selective chemical probe we have developed. The
      combination of MRM identification and analysis of the functional activity, as in
      the case of CYP3A4, provides a protocol which can be extended to other functional
      enzyme studies with wide application in pharmaceutical research. 

PMID- 24920407
TI  - A microscopic view of the yielding transition in concentrated emulsions.
AB  - We use a custom shear cell coupled to an optical microscope to investigate at the
      particle level the yielding transition in concentrated emulsions subjected to an
      oscillatory shear deformation. By performing experiments lasting thousands of
      cycles on samples at several volume fractions and for a variety of applied strain
      amplitudes, we obtain a comprehensive, microscopic picture of the yielding
      transition. We find that irreversible particle motion sharply increases beyond a
      volume-fraction dependent critical strain, which is found to be in close
      agreement with the strain beyond which the stress-strain relation probed in
      rheology experiments significantly departs from linearity. The shear-induced
      dynamics are very heterogenous: quiescent particles coexist with two distinct
      populations of mobile and 'supermobile' particles. Dynamic activity exhibits
      spatial and temporal correlations, with rearrangements events organized in bursts
      of motion affecting localized regions of the sample. Analogies with other sheared
      soft materials and with recent work on the transition to irreversibility in
      sheared complex fluids are briefly discussed. 

PMID- 24920408
TI  - Contemporary Infrapopliteal Intervention for Limb Salvage and Wound Healing.
AB  - Infrapopliteal arterial disease is a significant cause of critical limb ischemia
      (CLI), whether single-segment or multisegment disease. The collaboration between
      the tremendous advancements in endovascular technology and the refinement of
      endovascular techniques has renewed the classic infrapopliteal interventions
      during the past decade. With this paradigm shift in the treatment of CLI, the
      role of a comprehensive approach of different disciplines for tissue loss is
      becoming greater. Given the increasing global burden of CLI, we review the
      cutting-edge diagnostic and endovascular approaches to infrapopliteal artery
      disease, and the importance of wound management in optimizing clinical outcomes.

PMID- 24920409
TI  - Clinical Management of Takotsubo Cardiomyopathy.
AB  - Takotsubo cardiomyopathy was first reported by Sato et al at Hiroshima City
      Hospital in 1990 and has become increasingly recognized worldwide. In the
      clinical setting, takotsubo cardiomyopathy is an important disease that must be
      differentiated from AMI promptly for the appropriate management. Prognosis of
      takotsubo cardiomyopathy is generally favorable, but serious complications can
      occur, especially in the early stage. In this review, we summarize the current
      knowledge on the clinical management of takotsubo cardiomyopathy.

PMID- 24920410
TI  - Impact of rotational atherectomy on heavily calcified, unprotected left main
      disease.
AB  - BACKGROUND: There is little data on percutaneous coronary intervention (PCI)
      using rotational atherectomy (Rota) for severely calcified unprotected left main
      (ULM) lesions. METHODS AND RESULTS: Between January 2005 and August 2011, 64
      consecutive patients who underwent drug-eluting stent implantation using Rota
      were retrospectively evaluated. Of these, 54.7% and 20.3% patients had diabetes
      and were undergoing hemodialysis (HD), respectively. The mean EuroSCORE and
      SYNTAX score was 5.6 and 35.4, respectively. Procedural success, defined as
      residual stenosis <30%, was achieved in 95.3% of patients without fatal
      complications. Periprocedural myocardial infarction occurred in 7.8% patients. At
      the 1-year follow up, cardiac death was observed in 6.3% of patients, and target
      lesion revascularization (TLR) and TLR in the main branch (TLR-MB) were required
      in 18.8% and 10.9% patients, respectively. Optimal stent expansion was achieved
      in the majority of 33 patients with available intravascular ultrasound (IVUS)
      data. However, 5 of 9 HD patients who underwent IVUS required TLR-MB despite
      optimal stent expansion. The rate of TLR-MB was significantly lower in the non-HD
      patients than in the HD patients (2.1% vs. 46.2%; P=0.003). CONCLUSIONS: PCI
      using Rota for calcified ULM lesions might guarantee high procedural success and
      a low complication rate. Although acceptable results were obtained at the 1-year
      follow up for non-HD patients, the rate of TLR-MB was considerably high for HD
      patients despite optimal stent expansion.

PMID- 24920411
TI  - Structure of tetraalkylammonium ionic liquids in the interlayer of modified
      montmorillonite.
AB  - We perform molecular dynamics simulations of tetraalkylammonium ionic liquids
      confined in the interlayer of montmorillonite (MMT). We study the structure and
      energetics of the systems, which consist of cations with two different alkyl
      chain lengths and several ionic liquid concentrations. The results we obtained
      for the structure, namely the presence of a strong layering in all systems and
      the formation of nonpolar domains with interdigitated alkyl chains in some cases,
      are largely consistent with previous surface force balance experiments performed
      on similar systems. Finally, we show that swelling of the organo-modified MMT by
      a large amount of ionic liquid seems energetically favorable in all cases. 

PMID- 24920406
TI  - Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to
      clinical application (review).
AB  - Over the last few years, clinical trials with BRAF and mitogen-activated
      protein/extracellular signal-regulated kinase (MEK) inhibitors have shown
      significant clinical activity in melanoma, but only a fraction of patients
      respond to these therapies, and development of resistance is frequent. This has
      prompted a large set of preclinical studies looking at several new combinatorial
      approaches of pathway- or target-specific inhibitors. At least five main drug
      association strategies have been verified in vitro and in preclinical models. The
      most promising include: i) vertical targeting of either MEK or phosphoinositide-3
      kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways, or their combined
      blockade; ii) association of receptor tyrosine kinases (RTKs) inhibitors with
      other pro-apoptotic strategies; iii) engagement of death receptors in combination
      with MEK-, mTOR/PI3K-, histone deacetylase (HDAC)-inhibitors, or with anti
      apoptotic molecules modulators; iv) strategies aimed at blocking anti-apoptotic
      proteins belonging to B-cell lymphoma (Bcl-2) or inhibitors of apoptosis (IAP)
      families associated with MEK/BRAF/p38 inhibition; v) co-inhibition of other
      molecules important for survival [proteasome, HDAC and Signal transducers and
      activators of transcription (Stat)3] and the major pathways activated in
      melanoma; vi) simultaneous targeting of multiple anti-apoptotic molecules. Here
      we review the anti-melanoma efficacy and mechanism of action of the above
      mentioned combinatorial strategies, together with the potential clinical
      application of the most promising studies that may eventually lead to therapeutic
      benefit.

PMID- 24920412
TI  - Reduction of Fe(III) oxides by phylogenetically and physiologically diverse
      thermophilic methanogens.
AB  - Three thermophilic methanogens (Methanothermobacter thermautotrophicus,
      Methanosaeta thermophila, and Methanosarcina thermophila) were investigated for
      their ability to reduce poorly crystalline Fe(III) oxides (ferrihydrite) and the
      inhibitory effects of ferrihydrite on their methanogenesis. This study
      demonstrated that Fe(II) generation from ferrihydrite occurs in the cultures of
      the three thermophilic methanogens only when H2 was supplied as the source of
      reducing equivalents, even in the cultures of Mst. thermophila that do not grow
      on and produce CH4 from H2/CO2. While supplementation of ferrihydrite resulted in
      complete inhibition or suppression of methanogenesis by the thermophilic
      methanogens, ferrihydrite reduction by the methanogens at least partially
      alleviates the inhibitory effects. Microscopic and crystallographic analyses on
      the ferrihydrite-reducing Msr. thermophila cultures exhibited generation of
      magnetite on its cell surfaces through partial reduction of ferrihydrite. These
      findings suggest that at least certain thermophilic methanogens have the ability
      to extracellularly transfer electrons to insoluble Fe(III) compounds, affecting
      their methanogenic activities, which would in turn have significant impacts on
      materials and energy cycles in thermophilic anoxic environments.

PMID- 24920413
TI  - Classroom conditions and CO2 concentrations and teacher health symptom reporting
      in 10 New York State Schools.
AB  - This study assessed the relationship between teacher-reported symptoms and
      classroom carbon dioxide (CO2 ) concentrations. Previous studies have suggested
      that poor indoor ventilation can result in higher levels of indoor pollutants,
      which may affect student and teacher health. Ten schools (9 elementary, 1
      combined middle/high school) in eight New York State school districts were
      visited over a 4-month period in 2010. Carbon dioxide concentrations were
      measured in classrooms over 48-h, and teachers completed surveys assessing
      demographic information and self-reported symptoms experienced during the current
      school year. Data from 64 classrooms (ranging from 1 to 9 per school) were linked
      with 68 teacher surveys (for four classrooms, two surveys were returned).
      Overall, approximately 20% of the measured classroom CO2 concentrations were
      above 1000 parts per million (ppm), ranging from 352 to 1591 ppm. In multivariate
      analyses, the odds of reporting neuro-physiologic (i.e., headache, fatigue,
      difficulty concentrating) symptoms among teachers significantly increased (OR =
      1.30, 95% CI = 1.02-1.64) for every 100 ppm increase in maximum classroom CO2
      concentrations and were non-significantly increased in classrooms with above
      median proportions of CO2 concentrations greater than 1000 ppm (OR = 2.26, 95% CI
      = 0.72-7.12). 

PMID- 24920421
TI  - Factors associated with systemic hypertension in asthma.
AB  - PURPOSE: Asthmatics have unique characteristics that may influence cardiovascular
      morbidity. We tested the association of lower airway caliber, obstructive sleep
      apnea (OSA), and other asthma-related factors, with systemic hypertension (HTN).
      METHODS: Asthma individuals at specialty clinics completed the Sleep Apnea scale
      of the Sleep Disorders Questionnaire (SA-SDQ). Medical records were reviewed for
      diagnosed HTN, OSA and comorbidities, spirometry, and current medications. FEV1%
      predicted was categorized as >= 80 (reference), 70-79, 60-69, and < 60. SA-SDQ >=
      36 for men and >= 32 for women defined high OSA risk. RESULTS: Among 812
      asthmatics (mean age +/- standard deviation: 46 +/- 14 years), HTN was diagnosed
      in 191 (24%), OSA in 65 (8%), and OSA or high OSA risk (combined OSA variable) in
      239 (29%). HTN was more prevalent in lower FEV1% categories (p < 0.0001), in
      subjects with OSA, and those with combined OSA variable (55 vs. 21% and 46 vs.
      14%, respectively, both p < 0.0001). With adjustment for covariates, associations
      with HTN remained significant for some FEV1% categories (70-79% odds ratio = 1.60
      [95% CI 0.90-2.87]; 60-69% 2.73 [1.28-5.79]; < 60% 0.96 [0.43-2.14]), and for OSA
      (2.20 [1.16-4.19]). The combined OSA variable in comparison with OSA alone
      demonstrated a stronger association with HTN (3.17 [1.99-5.04]) in a reiteration
      of this model. Inhaled corticosteroids (ICS) at lowest doses, in comparison to no
      ICS use had an independent "protective" association with HTN (0.44 [0.22-0.90]).
      CONCLUSIONS: In this young population, worse lower airways obstruction and OSA
      were associated with HTN. In contrast, lower ICS doses attenuated likelihood for
      HTN. Adequate control of airway inflammation at appropriate ICS doses, and
      screening for OSA may reduce the burden of HTN in asthma.

PMID- 24920422
TI  - Impact of dietary macronutrient distribution on BMI and cardiometabolic outcomes
      in overweight and obese children and adolescents: a systematic review.
AB  - The present systematic review examined the effectiveness of weight management
      interventions comparing diets with varying macronutrient distributions on BMI and
      cardiometabolic risk factors in overweight or obese children and adolescents. A
      systematic search of seven databases for the period 1975-2013 identified 14
      eligible randomized or quasi-randomized controlled trials conducted with 6-18
      year-old subjects. Seven trials compared a low-fat (<= 33% energy or < 40 g/day)
      to an isocaloric (n = 2) or ad libitum (n = 5) low-carbohydrate diet (< 20%
      energy or < 60 g/day). Meta-analysis indicated a greater reduction in BMI in the
      low-carbohydrate group immediately after dietary intervention; however, the
      quality of the studies was limited and cardiometabolic benefits were
      inconsistent. Six trials compared increased-protein diets (19-30% energy) to
      isocaloric standard-protein diets (15-20% energy) and one compared an increased
      fat diet (40% energy) to an isocaloric standard-fat diet (27% energy); there were
      no differences in outcomes in these studies. Current evidence suggests that
      improved weight status can be achieved in overweight or obese children and
      adolescents irrespective of the macronutrient distribution of a reduced-energy
      diet. Tailoring the macronutrient content to target specific cardiometabolic risk
      factors, such as a low-carbohydrate diet to treat insulin resistance, may be
      possible, but further research is needed before specific recommendations can be
      made.

PMID- 24920423
TI  - Aberrant hypomethylation-mediated AGR2 overexpression induces an aggressive
      phenotype in ovarian cancer cells.
AB  - The metastatic properties of cancer cells result from genetic and epigenetic
      alterations that lead to the abnormal expression of key genes regulating tumor
      phenotypes. Recent discoveries suggest that aberrant DNA methylation provides
      cancer cells with advanced metastatic properties; however, the precise regulatory
      mechanisms controlling metastasis-associated genes and their roles in metastatic
      transformation are largely unknown. We injected SK-OV-3 human ovarian cancer
      cells into the perineum of nude mice to generate a mouse model that mimics human
      ovarian cancer metastasis. We analyzed the mRNA expression and DNA methylation
      profiles in metastasized tumor tissues in the mice. The pro-oncogenic anterior
      gradient 2 (AGR2) gene showed increased mRNA expression and hypomethylation at
      CpG sites in its promoter region in the metastatic tumor tissues compared with
      the cultured SK-OV-3 cells. We identified crucial cytosine residues at CpG sites
      in the AGR2 promoter region. Treatment with the DNA methyltransferase inhibitor 5
      aza-2'-deoxycytidine reduced the level of CpG methylation in the AGR2 promoter
      and increased the level of AGR2 expression. Next, we explored the functional role
      of AGR2 in the metastatic transformation of SK-OV-3 cells. SK-OV-3 cells
      overexpressing AGR2 showed increased migratory and invasive activity. Our results
      indicate that DNA methylation within the AGR2 promoter modulates more aggressive
      cancer cell phenotypes.

PMID- 24920424
TI  - Preliminary report on a new concept stent prototype designed for venous implant.
AB  - Venous obstruction at iliocaval level in both forms, primary and secondary, is a
      significant cause of severe chronic venous insufficiency. A new therapeutic
      approach to this pathology emerged with the introduction of stenting procedures
      that proved effective, leading to good long-term results. However, at present,
      the majority of implanted stents have been designed for arterial implant and this
      can pose a limit in particular districts. The purpose of this preliminary acute
      study was to verify the deliverability and safety of a new stent specially
      designed for venous-vessel implant. We assess the safety and deliverability of
      two braided, self-expanding, nickel-titanium stents (Jotec GmbH, Hechingen,
      Germany) specially designed for endovascular implant in veins. The two stents,
      despite being based on the same concept, have a different design: stent A
      presents a proximal tapering shape specially designed to reduce migration, while
      stent B does not. Both of them are enlarged at their distal extremity and present
      variable radial force the length of the stent itself, the said force becoming
      very high in the intermediate segment. Stents were implanted in the internal
      jugular vein of a sheep, showing optimal deliverability. The completion
      venography showed the migration of stent B into the right atrium. Stent A
      maintained its location, confirmed by intravascular ultrasound examination. No
      scaffolding effect was detected and an adequate adherence and adaptability to the
      vein wall was obtained. In conclusions, the stent A design matches the
      characteristics required by vein implants. Stability is achieved even where
      difficult anatomical conditions apply, such as in the jugular vein. Deployment is
      easy and precise in a given landing zone. Radial resistive force is very high, as
      required in specific vein districts, but is also associated with good
      flexibility. Following this preliminary acute report, further studies are
      required. 

PMID- 24920425
TI  - Preliminary study on retinal vascular and oxygen-related changes after long-term
      silicone oil and foldable capsular vitreous body tamponade.
AB  - Silicone oil has been the only long-term vitreous substitute used in the
      treatment of retinal detachment since 1962 by Cibis. Nevertheless, its effects on
      retinal vascular morphology and oxygen supply to the retina are ambiguous in
      current research. We previously invented a foldable capsular vitreous body (FCVB)
      to use as a new vitreous substitute in the treatment of severe retinal
      detachment, but its effects on the retinal vessel were unknown. Therefore, in
      this study, a standard three-port pars plana vitrectomy (PPV) was performed on
      the right eye of each rabbit and then silicone oil and FCVB were injected into
      the vitreous cavity as vitreous substitutes. After 180 days of retention, the
      retinal vascular morphology did not display any distinct abnormalities, and
      hypoxia-induced factor-1alpha (HIF-1alpha) and vascular endothelial growth factor
      (VEGF) did not vary markedly during the observation period in silicone oil
      tamponade- and FCVB-implanted eyes. This study may suggest that silicone oil and
      FCVB tamponade in rabbit eyes did not cause retinal vascular pathologic changes
      or retinal hypoxia for 180 days. 

PMID- 24920426
TI  - N-glycoprotein surfaceomes of four developmentally distinct mouse cell types.
AB  - PURPOSE: Detailed knowledge of cell surface proteins present during early
      embryonic development remains limited for most cell lineages. Due to the
      relevance of cell surface proteins in their functional roles controlling cell
      signaling and their utility as accessible, nongenetic markers for cell
      identification and sorting, the goal of this study was to provide new information
      regarding the cell surface proteins present during early mouse embryonic
      development. EXPERIMENTAL DESIGN: Using the cell surface capture technology, the
      cell surface N-glycoproteomes of three cell lines and one in vitro differentiated
      cell type representing distinct cell fates and stages in mouse embryogenesis were
      assessed. RESULTS: Altogether, more than 600 cell surface N-glycoproteins were
      identified represented by >5500 N-glycopeptides. CONCLUSIONS AND CLINICAL
      RELEVANCE: The development of new, informative cell surface markers for the
      reliable identification and isolation of functionally defined subsets of cells
      from early developmental stages will advance the use of stem cell technologies
      for mechanistic developmental studies, including disease modeling and drug
      discovery.

PMID- 24920427
TI  - Acute toxicity of copper, lead, cadmium, and zinc to early life stages of white
      sturgeon (Acipenser transmontanus) in laboratory and Columbia River water.
AB  - Populations of white sturgeon (Acipenser transmontanus) are in decline in North
      America. This is attributed, primarily, to poor recruitment, and white sturgeon
      are listed as threatened or endangered in several parts of British Columbia,
      Canada, and the United States. In the Columbia River, effects of metals have been
      hypothesized as possible contributing factors. Previous work has demonstrated
      that early life stage white sturgeon are particularly sensitive to certain
      metals, and concerns over the level of protectiveness of water quality standards
      are justified. Here we report results from acute (96-h) toxicity tests for copper
      (Cu), cadmium (Cd), zinc (Zn), and lead (Pb) from parallel studies that were
      conducted in laboratory water and in the field with Columbia River water. Water
      effect ratios (WERs) and sensitivity parameters (i.e., median lethal
      accumulations, or LA50s) were calculated to assess relative bioavailability of
      these metals in Columbia River water compared to laboratory water, and to
      elucidate possible differences in sensitivity of early life stage white sturgeon
      to the same concentrations of metals when tested in the different water sources.
      For Cu and Pb, white sturgeon toxicity tests were initiated at two life stages, 8
      and 40 days post-hatch (dph), and median lethal concentrations (LC50s) ranged
      between 9-25 MUg Cu/L and 177-1,556 MUg Pb/L. LC50s for 8 dph white sturgeon
      exposed to Cd in laboratory water and river water were 14.5 and 72 MUg/L,
      respectively. Exposure of 8 dph white sturgeon to Zn in laboratory and river
      water resulted in LC50s of 150 and 625 MUg/L, respectively. Threshold
      concentrations were consistently less in laboratory water compared with river
      water, and as a result, WERs were greater than 1 in all cases. In addition, LA50s
      were consistently greater in river water exposures compared with laboratory
      exposures in all paired tests. These results, in combination with results from
      the biotic ligand model, suggest that the observed differences in toxicity
      between river water exposures and laboratory water exposures were not entirely
      due to differences in water quality and metal bioavailability but rather in
      combination with differences in fish sensitivity. It is hypothesized that
      differences in concentrations of calcium in the different water sources might
      have resulted in differences in acquired sensitivity of sturgeon to metals.
      Canadian water quality guidelines, US national criteria for the protection of
      aquatic life, and water quality criteria for the state of Washington were less
      than LC50 values for all metals and life stages tested in laboratory and Columbia
      River water. With the exception, however, that 40 dph white sturgeon exposed to
      Cu in laboratory water resulted in threshold values that bordered US national
      criteria and criteria for the state of Washington.

PMID- 24920428
TI  - The effect of aerosol optical depth on rainfall with reference to meteorology
      over metro cities in India.
AB  - Rainfall is a key link in the global water cycle and a proxy for changing
      climate; therefore, proper assessment of the urban environment's impact on
      rainfall will be increasingly important in ongoing climate diagnostics and
      prediction. Aerosol optical depth (AOD) measurements on the monsoon seasons of
      the years 2008 to 2010 were made over four metro regional hotspots in India. The
      highest average of AOD was in the months of June and July for the four cities
      during 3 years and lowest was in September. Comparing the four regions, Kolkata
      was in the peak of aerosol contamination and Chennai was in least. Pearson
      correlation was made between AOD with climatic parameters. Some changes in the
      parameters were found during drought year. Temperature, cloud parameters, and
      humidity play an important role for the drought conditions. The role of aerosols,
      meteorological parameters, and their impacts towards the precipitation during the
      monsoon was studied.

PMID- 24920429
TI  - Synergic degradation of diesel by Scirpus triqueter and its endophytic bacteria.
AB  - The endophytic bacterium isolated from Scirpus triqueter was proved to be an oil
      degraded bacterium. A pot experiment was conducted to investigate the removal
      ratio of diesel under the combined effect of oil-degraded microorganism
      (Pseudomonas sp. J4AJ) and S. triqueter. The effect of diesel on plant growth
      parameters, soil enzymes and microbial community was assessed after 60 days. The
      results showed that the soils which were planted with S. triqueter and inoculated
      with J4AJ displayed the highest removal ratio (54.51 +/- 0.15%) after 60-day
      experiment. However, the removal ratio of J4AJ-treated soils was 38.97 +/- 0.55%.
      Diesel was toxic to S. triqueter, as evidenced by growth inhibition during the
      experimental period. However, the plant height and stem biomass in the soils
      inoculated with J4AJ significantly increased. The combined effect of S. triqueter
      and J4AJ improved the enzyme activities of the catalase and dehydrogenase in the
      contaminated soil. The diversity index in soils under the effect of S. triqueter
      combined with J4AJ was lower than that of the other soil samples. The principal
      analysis of phospholipid fatty acid signatures revealed that the combined effect
      of S. triqueter and J4AJ increased the differences of soil microbial community
      structure with the other treatments.

PMID- 24920430
TI  - Antioxidant responses in clam Venerupis philippinarum exposed to environmental
      pollutant hexabromocyclododecane.
AB  - The objective of this study was to assess the potential toxic effects of
      hexabromocyclododecane (HBCD) on tissues of clam Venerupis philippinarum using
      parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers
      including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST),
      superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and
      lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were
      analyzed after a 1-, 3-, 6-, 10-, and 15-day exposure to seawater containing HBCD
      at environmentally related concentrations, respectively. The results showed that
      the activity of most antioxidant enzymes increased, and different trends were
      detected with exposure time extending. The oxidative stress could be obviously
      caused in the gills and digestive glands under the experimental conditions. This
      could provide useful information for toxic risk assessment of environmental
      pollutant HBCD. 

PMID- 24920431
TI  - Toxic effect of metal cation binary mixtures to the seaweed Gracilaria
      domingensis (Gracilariales, Rhodophyta).
AB  - The macroalga Gracilaria domingensis is an important resource for the food,
      pharmaceutical, cosmetic, and biotechnology industries. G. domingensis is at a
      part of the food web foundation, providing nutrients and microelements to upper
      levels. As seaweed storage metals in the vacuoles, they are considered the main
      vectors to magnify these toxic elements. This work describes the evaluation of
      the toxicity of binary mixtures of available metal cations based on the growth
      rates of G. domingensis over a 48-h exposure. The interactive effects of each
      binary mixture were determined using a toxic unit (TU) concept that was the sum
      of the relative contribution of each toxicant and calculated using the ratio
      between the toxicant concentration and its endpoint. Mixtures of Cd(II)/Cu(II)
      and Zn(II)/Ca(II) demonstrated to be additive; Cu(II)/Zn(II), Cu(II)/Mg(II),
      Cu(II)/Ca(II), Zn(II)/Mg(II), and Ca(II)/Mg(II) mixtures were synergistic, and
      all interactions studied with Cd(II) were antagonistic. Hypotheses that explain
      the toxicity of binary mixtures at the molecular level are also suggested. These
      results represent the first effort to characterize the combined effect of
      available metal cations, based on the TU concept on seaweed in a total controlled
      medium. The results presented here are invaluable to the understanding of seaweed
      metal cation toxicity in the marine environment, the mechanism of toxicity action
      and how the tolerance of the organism. 

PMID- 24920432
TI  - Engineering the metabolism of the phenylurea herbicide chlortoluron in
      genetically modified Arabidopsis thaliana plants expressing the mammalian
      cytochrome P450 enzyme CYP1A2.
AB  - Transgenic Arabidopsis thaliana plants were generated by introduction of the
      human P450 CYP1A2 gene, which metabolizes a number of herbicides, insecticides
      and industrial chemicals. Transgenic A. thaliana plants expressing CYP1A2 gene
      showed remarkable resistance to the phenylurea herbicide chlortoluron (CTU)
      supplemented either in plant growth medium or sprayed on foliar parts of the
      plants. HPLC analyses showed a strong reduction in CTU accumulation in planta
      supporting the tolerance of transgenic lines to high concentrations of CTU.
      Besides increased herbicide tolerance, expression of CYP1A2 resulted in no other
      visible phenotype in transgenic plants. Our data indicate that CYP1A2 can be used
      as a selectable marker for plant transformation, allowing efficient selection of
      transgenic lines in growth medium and/or in soil-grown plants. Moreover, these
      transgenic plants appear to be useful for herbicide resistance as well as
      phytoremediation of environmental contaminants. 

PMID- 24920433
TI  - [Majocchi granuloma. Advantages of optical brightener staining in a case report].
AB  - A patient presented with Majocchi granuloma caused by T. rubrum. By the use of
      optical brighteners, fungal elements in the deep dermis could be detected more
      sensitive than with PAS staining. Healing was achieved by long-term use of oral
      terbinafine (250 mg per day 12 weeks, followed by 250 mg once per week for
      another 12 weeks). 

PMID- 24920434
TI  - [Acne inversa: influence of associated factors in the extent of the disease and
      the result of surgery].
AB  - BACKGROUND: Acne inversa is a chronic inflammatory disease with fistulas and
      abscesses of unknown etiology. A number of trigger factors have been identified,
      but their influence on pathogenesis and severity of the disease is controversial.
      METHODS: In a retrospective study we analyzed 84 patients with AI who underwent
      113 surgical procedures. Well-known external and internal trigger factors as well
      as the surgical procedure and its outcome together with parameters of quality of
      life and patient satisfaction were assessed. RESULTS: The median severity of
      disease (Sartorius score) was 43.4 without any gender differences. The amount of
      smokers was extraordinarily high with 93%, but there was no correlation between
      smoking and disease severity. Obesity (77% in all patients), the age of primary
      manifestation of AI, family history of AI, atypical locations, and history of
      severe acne were significantly associated with the Sartorius score and therefore
      with AI severity. Except for age of primary manifestation and history of severe
      acne, the mentioned factors were independent predictors for disease severity in
      multivariate analysis. The postsurgical recurrence rate was 12.4% and
      significantly higher in heavy smokers. However, there was no relation between
      recurrence rate and wound closure. The evaluation of patients' self- assessment
      on life quality showed a postsurgical improvement of 70%. CONCLUSION: The wide
      surgical excision of all lesions followed by spontaneous healing or split-skin
      grafting leads to a reasonable recurrence rate and improves the affected
      patients' quality of life for a prolonged period of time.

PMID- 24920435
TI  - Use of IOTA simple rules for diagnosis of ovarian cancer: meta-analysis.
AB  - OBJECTIVES: To present data on prospective evaluation of the International
      Ovarian Tumor Analysis (IOTA) 'simple-rules' tool for the diagnosis of ovarian
      cancer and to perform a meta-analysis of studies that utilized the same
      diagnostic method. METHODS: In the present study a level-II ultrasound operator
      systematically assessed the tumors of women with an ultrasound diagnosis of
      adnexal tumor(s) according to the IOTA simple-rules protocol to determine the
      risk of the tumor being malignant. The results of simple rules were compared with
      the 'pattern recognition' method and with histological findings. This validation
      study was included in the subsequent meta-analysis, for which we searched
      MEDLINE, EMBASE and Cochrane from the publication of the first study in 2008. The
      terms used were 'simple rules', 'simple rules ovarian', 'ovar tumor' and
      'ultrasound'. Quality assessment was performed using the modified Quality
      Assessment of the Diagnostic Accuracy of Studies (QUADAS-2) checklist. Random
      effects meta-analysis was used to calculate pooled estimates of sensitivity and
      specificity for the simple-rules tool, and meta-regression was used to
      investigate heterogeneity across the studies. RESULTS: Three hundred and three
      women were included in the validation study with 168 (55.4%) benign, 19 (6.3%)
      borderline and 116 (38.3%) malignant tumors on histological examination. The
      rules were applicable in 237 (78.2%) of the tumors and for these tumors,
      sensitivity was 96.2% (95% CI, 90.5-99.0%) and specificity was 88.6% (95% CI,
      82.0-93.5%). Six of the 88 discovered studies were included in the meta-analysis
      along with the current validation study, which resulted in inclusion of a total
      of 3568 patients. When the meta-analysis was performed the pooled sensitivity
      (when the rules were applicable) was 93% (95% CI, 90-96%) (I(2)  = 32.1%) and the
      pooled specificity was 95% (95% CI, 93-97%) (I(2)  = 78.1%). Heterogeneity was
      observed across the studies. Sensitivity was higher and specificity lower in the
      study populations in which the prevalence of malignant tumors was greatest.
      CONCLUSION: The simple rules protocol could be used in 76-89% of tumors and is an
      accurate test for the diagnosis of ovarian cancer. Assessment by an ultrasound
      expert is required when the protocol cannot be applied.

PMID- 24920436
TI  - Turning a water and oil insoluble cisplatin derivative into a nanoparticle
      formulation for cancer therapy.
AB  - The formulation of water insoluble organic compounds into nanoparticles has
      become a widely established method for enhancing the delivery and efficacy of
      cancer therapeutics. Therefore, a comparable approach when applied to water
      insoluble inorganic compounds should also promote similar advantages. Herein, we
      have successfully formulated insoluble iodinated cisplatin (CDDP-I) into an LPI
      NPs (lipid-coated iodinated CDDP nanoparticles). Two separate microemulsions were
      combined, each containing a precursor for the synthesis of CDDP-I. The resulting
      CDDP-I precipitate was then coated with an anionic lipid and dispersed in water
      with the help of an additional lipid. This method allows us to effectively
      encapsulate CDDP-I and was able to achieve a considerable drug loading of 82 wt%.
      Administered LPI NPs demonstrated high level accumulation in tumor tissues and
      exhibited an anti-cancer activity comparable to free CDDP in two melanoma
      xenograft models without inducing nephrotoxicity. The benefits offered through
      this delivery formulation are not unique to CDDP-I, as this versatile platform
      may be extended to the formulation of other inorganic compounds that are both
      water and oil insoluble into nanoparticles for superior anti-cancer efficacy. 

PMID- 24920438
TI  - The sHunt for better breathing in heart failure with preserved ejection fraction.

PMID- 24920437
TI  - Central changes associated with chronic pelvic pain and endometriosis.
AB  - BACKGROUND: Chronic pelvic pain (CPP) is a significant public health problem with
      1 million affected women in the UK. Although many pathologies are associated with
      CPP, the pain experienced is often disproportionate to the extent of disease
      identified and frequently no pathology is found (chronic pelvic pain syndrome).
      The central nervous system (CNS) is central to the experience of pain and chronic
      pain conditions in general are associated with alterations in both the structure
      and function of the CNS. This review describes the available evidence for central
      changes in association with conditions presenting with CPP. METHODS: A detailed
      literature search was performed to identify relevant papers, however, this is not
      a systematic review. RESULTS: CPP is associated with central changes similar to
      those identified in other pain conditions. Specifically these include,
      alterations in the behavioural and central response to noxious stimulation,
      changes in brain structure (both increases and decreases in the volume of
      specific brain regions), altered activity of both the hypothalamic-pituitary
      adrenal axis and the autonomic nervous system (ANS) and psychological distress.
      CONCLUSIONS: The evidence reviewed in this paper demonstrates that CPP is
      associated with significant central changes when compared with healthy pain-free
      women. Moreover, the presence of these changes has the potential to both
      exacerbate symptoms and to predispose these women to the development of
      additional chronic conditions. These findings support the use of adjunctive
      medication targeting the CNS in these women.

PMID- 24920439
TI  - Burden of post-herpetic neuralgia in a sample of UK residents aged 50 years or
      older: findings from the Zoster Quality of Life (ZQOL) study.
AB  - BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication of
      herpes zoster (shingles). As a chronic condition, PHN can have a substantial
      adverse impact on patients' lives. However, UK-specific data concerning the
      burden of PHN on individual patients, healthcare systems and wider society, are
      lacking. As the first UK-wide cross-sectional study of its kind, The Zoster
      Quality of Life (ZQOL) study was designed to address these concerns. METHODS:
      Patients (n = 152) with a confirmed diagnosis of PHN (defined as pain persisting
      >= 3 months following rash onset) and aged >=50 years were recruited from primary
      and secondary/tertiary care centres throughout the UK. All patients completed
      validated questionnaires, including the Zoster Brief Pain Inventory (ZBPI), the
      Medical Outcomes Study Short-Form 36 (SF-36), the EuroQol-5 Dimensions (EQ-5D)
      and the Treatment Satisfaction with Medication (TSQM) questionnaire. Where
      available, mean patient population scores on these questionnaires were compared
      to scores derived from age-matched normative samples to quantify the burden
      associated with PHN. RESULTS: Despite numerous consultations with healthcare
      professionals and receiving multiple medications for the management of their PHN,
      the majority of patients reported being in pain 'most of the time' or 'all of the
      time'. A total of 59.9% (n = 91) of all PHN patients reported pain in the
      preceding 24 hours to assessment at levels (ZBPI worst pain >= 5) typically
      considered to have a significant impact on Health Related Quality of Life
      (HRQoL). Accordingly, scores for SF-36 and EQ-5D indicated significant deficits
      in HRQoL among PHN patients compared to age-matched norms (p < 0.05) and patients
      reported being dissatisfied with the perceived efficacy of therapies received for
      the management of PHN. Increased pain severity was observed among older
      participants and higher levels of pain severity were associated with greater
      HRQoL deficits. CONCLUSIONS: The inadequate relief provided by PHN therapies
      available in the UK is associated with a significant burden among PHN patients in
      terms of pain severity and deficits in HRQoL which may persist for years.
      Therefore, alternative means such as prevention of shingles and PHN, are
      essential for reducing the impact on individual patients, healthcare systems and
      society as a whole.

PMID- 24920440
TI  - In vitro comparison of the cytotoxicity and water sorption of two different
      denture base systems.
AB  - PURPOSE: Denture base resins have the potential to cause cytotoxicity in vivo,
      and the mechanical properties of resins are affected by water sorption. There is
      a correlation between residual monomer and water sorption. Thus, the purpose of
      this study was to evaluate water sorption and cytotoxicity of light-activated
      urethane dimethacrylate (UDMA) denture base resin compared to a conventional heat
      activated polymethyl methacrylate (PMMA) resin. MATERIALS AND METHODS: Two
      denture base resins, heat-activated PMMA (Meliodent) and light-activated UDMA
      (Eclipse), were used in this study. Cytotoxicity (5 * 1 mm(2) ) and water
      sorption (1 * 1 mm(2) ) specimens were made following the manufacturers'
      instructions (n = 10). Cytotoxicity tests of denture base resins were performed
      according to ISO10993-5:1999, and water sorption was evaluated according to ISO
      1567:1997. ANOVA tests were employed for evaluating data (alpha = 0.05). RESULTS:
      There was no cytotoxic effect in either the PMMA or UDMA group. In addition,
      contrary to short-term water storage, a significantly lower water sorption value
      was shown for UDMA resins compared to PMMA resins in both 3- and 6-month storage
      periods (p = 0.043 and p = 0.002, respectively). CONCLUSION: The tested denture
      base materials adhered to the ISO standards for both cytotoxicity and water
      sorption. The cytotoxicity of the light-activated UDMA resin tested was
      statistically similar to that of the heat-activated PMMA resin; however, the UDMA
      resin exhibited decreased water sorption in long-term water storage.

PMID- 24920441
TI  - Preschool wheeze is not asthma: a clinical dilemma.
AB  - Recurrent wheezing is common in preschool children and often gets labelled as
      asthma. It is important to differentiate preschool wheeze from asthma through
      focused history, examination and exclusion of other serious conditions that may
      present as wheeze. Two different pragmatic clinical phenotypes viz. episodic
      viral wheeze (EVW) and multi-trigger wheeze (MTW) have been described although
      categories do not remain fixed and cross over is often seen in clinical practice.
      Episodic use of inhaled bronchodilators such as salbutamol when wheezy, is the
      mainstay of treatment along with non-pharmacological measures such as avoidance
      of environmental tobacco smoke and parental education. Inhaled corticosteroids
      are the first choice for maintenance therapy in MTW whereas montelukast may be
      useful when maintenance therapy is considered in EVW. Any maintenance therapy
      should be viewed as a trial and need to be discontinued in cases where no benefit
      has been demonstrated. Short term systemic steroid therapy should be reserved for
      excaerbation of wheezy symptoms where hospitalization is necessary. Prognosis is
      good in recurrent mild EVW although remission in atopic MTW is often not achieved
      and the children in the latter group go on to develop asthma. 

PMID- 24920443
TI  - Predicting change in symptoms of depression during the transition to university:
      the roles of BDNF and working memory capacity.
AB  - Studies on depression risk emphasize the importance of both cognitive and genetic
      vulnerability factors. The present study has provided the first examination of
      whether working memory capacity, the BDNF Val66Met polymorphism, and their
      interaction predict changes in symptoms of depression during the transition to
      university. Early in the semester, students completed a self-report measure of
      depressive symptoms and a modified version of the reading span task to assess
      working memory capacity in the presence of both neutral and negative distractors.
      Whole blood was genotyped for the BDNF Val66Met polymorphism. Students returned
      at the end of the semester to complete additional self-report questionnaires.
      Neither working memory capacity nor the BDNF Val66Met polymorphism predicted
      change in depressive symptoms either independently or in interaction with self
      reported semester difficulty. The BDNF Val66Met polymorphism, however, moderated
      the association between working memory capacity and symptom change. Among met
      carriers, lower working memory capacity in the presence of negative-but not
      neutral-distractors was associated with increased symptoms of depression over the
      semester. For the val/val group, working memory capacity did not predict symptom
      change. These findings contribute directly to biological and cognitive models of
      depression and highlight the importance of examining Gene * Cognition
      interactions when investigating risk for depression. 

PMID- 24920444
TI  - Scaffold Function of Ca2+-Dependent Protein Kinase: Tobacco Ca2+-DEPENDENT
      PROTEIN KINASE1 Transfers 14-3-3 to the Substrate REPRESSION OF SHOOT GROWTH
      after Phosphorylation.
AB  - A molecular mechanism to ensure signaling specificity is a scaffold. REPRESSION
      OF SHOOT GROWTH (RSG) is a tobacco (Nicotiana tabacum) transcription factor that
      is involved in gibberellin feedback regulation. The 14-3-3 proteins negatively
      regulate RSG by sequestering it in the cytoplasm in response to gibberellins. The
      N. tabacum Ca2+-dependent protein kinase NtCDPK1 was identified as an RSG kinase
      that promotes 14-3-3 binding of RSG by phosphorylation of RSG. CDPKs are unique
      sensor responders of Ca2+ that are only found in plants and some protozoans.
      Here, we report a scaffolding function of CDPK. 14-3-3 proteins bound to NtCDPK1
      by a new mode. Autophosphorylation of NtCDPK1 was necessary for the formation of
      the binding between NtCDPK1 and 14-3-3 but not for its maintenance. NtCDPK1
      formed a heterotrimer with RSG and 14-3-3. Furthermore, we found that NtCDPK1
      transfers 14-3-3 to RSG after phosphorylation of RSG and that RSG dissociates
      from NtCDPK1 as a complex with 14-3-3. These results suggest that NtCDPK1 is an
      interesting scaffolding kinase that increases the specificity and efficiency of
      signaling by coupling catalysis with scaffolding on the same protein.

PMID- 24920445
TI  - Functional and Evolutionary Analysis of the CASPARIAN STRIP MEMBRANE DOMAIN
      PROTEIN Family.
AB  - CASPARIAN STRIP MEMBRANE DOMAIN PROTEINS (CASPs) are four-membrane-span proteins
      that mediate the deposition of Casparian strips in the endodermis by recruiting
      the lignin polymerization machinery. CASPs show high stability in their membrane
      domain, which presents all the hallmarks of a membrane scaffold. Here, we
      characterized the large family of CASP-like (CASPL) proteins. CASPLs were found
      in all major divisions of land plants as well as in green algae; homologs outside
      of the plant kingdom were identified as members of the MARVEL protein family.
      When ectopically expressed in the endodermis, most CASPLs were able to integrate
      the CASP membrane domain, which suggests that CASPLs share with CASPs the
      propensity to form transmembrane scaffolds. Extracellular loops are not necessary
      for generating the scaffold, since CASP1 was still able to localize correctly
      when either one of the extracellular loops was deleted. The CASP first
      extracellular loop was found conserved in euphyllophytes but absent in plants
      lacking Casparian strips, an observation that may contribute to the study of
      Casparian strip and root evolution. In Arabidopsis (Arabidopsis thaliana), CASPL
      showed specific expression in a variety of cell types, such as trichomes,
      abscission zone cells, peripheral root cap cells, and xylem pole pericycle cells.

PMID- 24920446
TI  - Physiological correlates of positive symptoms in schizophrenia.
AB  - Patients with schizophrenia have been hypothesized to have a functional
      impairment in filtering irrelevant sensory information, which may result in
      positive symptoms such as hallucinations or delusions. Many evidences suggest
      that abnormalities in the event-related brain potentials (ERPs), resting state
      electroencephalography (EEG) and synchronized oscillatory activity of neurons may
      reflect core pathophysiological mechanisms of schizophrenia. Abnormalities in
      amplitude and latency of the ERPs reflecting aberrations in gating and
      difficulties in the detection of changes in auditory stimuli, as well as defects
      in stimuli evaluation and integration of information are common in patients with
      schizophrenia. This chapter highlights the findings of electrophysiological
      studies in schizophrenia dealing with early sensory perception and attention,
      automatic sensory detection of stimuli changes and cognitive evaluation and
      integration of information, relevant to the pathophysiological mechanisms
      underpinning hallucinations and delusions. Results of electrophysiological
      studies investigating the neural correlates of positive symptoms suggest aberrant
      intrinsic organization of functional brain networks. 

PMID- 24920442
TI  - Mechanisms of motivation-cognition interaction: challenges and opportunities.
AB  - Recent years have seen a rejuvenation of interest in studies of motivation
      cognition interactions arising from many different areas of psychology and
      neuroscience. The present issue of Cognitive, Affective, & Behavioral
      Neuroscience provides a sampling of some of the latest research from a number of
      these different areas. In this introductory article, we provide an overview of
      the current state of the field, in terms of key research developments and
      candidate neural mechanisms receiving focused investigation as potential sources
      of motivation-cognition interaction. However, our primary goal is conceptual: to
      highlight the distinct perspectives taken by different research areas, in terms
      of how motivation is defined, the relevant dimensions and dissociations that are
      emphasized, and the theoretical questions being targeted. Together, these
      distinctions present both challenges and opportunities for efforts aiming toward
      a more unified and cross-disciplinary approach. We identify a set of pressing
      research questions calling for this sort of cross-disciplinary approach, with the
      explicit goal of encouraging integrative and collaborative investigations
      directed toward them. 

PMID- 24920447
TI  - Physiological correlates of insomnia.
AB  - Insomnia is a prevalent sleep disorder that is typically comorbid with medical,
      psychiatric, and other sleep disorders. Yet, it is a disorder with its own course
      and morbidity that can persist if untreated. This chapter describes the
      physiological correlates of insomnia expressed during sleep and during the
      daytime. Together, the data from nighttime and daytime electrophysiology, event
      related brain potential recording, neuroimaging studies, sympathetic nervous
      system, and HPA axis monitoring all suggest that insomnia is a 24 h disorder of
      hyperarousal. 

PMID- 24920449
TI  - Early-return-to-work in the context of an intensification of working life and
      changing employment relationships.
AB  - PURPOSE: Many Western welfare states have introduced early-return-to-work
      policies, in which getting sick-listed people back to work before they have fully
      recovered is presented as a rather unproblematic approach. This reflects a belief
      in the ability of employers and the labour market to solve sickness absence.
      Against this background, the aim of this study was to analyse return-to-work
      practice in local workplace contexts, in relation to Swedish early-return-to-work
      policy. METHODS: Semi-structured interviews were conducted with 18 matched pairs
      of workers and managers. The material, comprising a total of 36 interviews, was
      analysed using qualitative content analysis. RESULTS: Three main themes were
      identified: (1) intensive workplaces and work conditions (2) employer support-a
      function of worker value and (3) work attachment and resistance to job
      transition. The results reflected the intensity of modern working life, which
      challenged return-to-work processes. Managers had different approaches to
      workers' return-to-work, depending on how they valued the worker. While managers
      used the discourse of 'new opportunities' and 'healthy change' to describe the
      transition process (e.g. relocation, unemployment and retirement), workers
      regularly experienced transitions as difficult and unjust. CONCLUSIONS: In the
      context of early-return-to-work policy and the intensity of modern working life,
      a great deal of responsibility was placed on workers to be adaptable to workplace
      demands in order to be able to return and stay at work. Overall, this study
      illustrates an emerging social climate where sick-listed workers are positioned
      as active agents who must take responsibility for sick leave and return-to-work
      process.

PMID- 24920450
TI  - Particle-induced pulmonary acute phase response may be the causal link between
      particle inhalation and cardiovascular disease.
AB  - Inhalation of ambient and workplace particulate air pollution is associated with
      increased risk of cardiovascular disease. One proposed mechanism for this
      association is that pulmonary inflammation induces a hepatic acute phase
      response, which increases risk of cardiovascular disease. Induction of the acute
      phase response is intimately linked to risk of cardiovascular disease as shown in
      both epidemiological and animal studies. Indeed, blood levels of acute phase
      proteins, such as C-reactive protein and serum amyloid A, are independent
      predictors of risk of cardiovascular disease in prospective epidemiological
      studies. In this review, we present and review emerging evidence that inhalation
      of particles (e.g., air diesel exhaust particles and nanoparticles) induces a
      pulmonary acute phase response, and propose that this induction constitutes the
      causal link between particle inhalation and risk of cardiovascular disease.
      Increased levels of acute phase mRNA and proteins in lung tissues,
      bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase
      response following pulmonary deposition of different kinds of particles including
      diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary
      acute phase response is dose-dependent and long lasting. Conversely, the hepatic
      acute phase response is reduced relative to lung or entirely absent. We also
      provide evidence that pulmonary inflammation, as measured by neutrophil influx,
      is a predictor of the acute phase response and that the total surface area of
      deposited particles correlates with the pulmonary acute phase response. We
      discuss the implications of these findings in relation to occupational exposure
      to nanoparticles.

PMID- 24920451
TI  - Childhood maltreatment, altered limbic neurobiology, and substance use relapse
      severity via trauma-specific reductions in limbic gray matter volume.
AB  - IMPORTANCE: Substance use disorders (SUDs) are among the most common sequelae of
      childhood maltreatment, yet the independent contributions of SUDs and childhood
      maltreatment to neurobiological changes and the effect of the latter on relapse
      risk (a critical variable in addiction treatment) are relatively unknown.
      OBJECTIVES: To identify structural neural characteristics independently
      associated with childhood maltreatment (CM; a common type of childhood
      adversity), comparing a sample with SUD with a demographically comparable control
      sample, and to examine the relationship between CM-related structural brain
      changes and subsequent relapse. DESIGN, SETTING, AND PARTICIPANTS: Structural
      magnetic resonance imaging study comparing 79 treatment-engaged participants with
      SUD in acute remission in inpatient treatment at a community mental health center
      vs 98 healthy control participants at an outpatient research center at an
      academic medical center. Both groups included individuals with a range of CM
      experiences. Participants with SUD were followed up prospectively for 90 days to
      assess relapse and relapse severity. INTERVENTION: Standard 12-step, recovery
      based, inpatient addiction treatment for all participants with SUD. MAIN OUTCOMES
      AND MEASURES: Gray matter volume (GMV), subsequent substance use relapse, days to
      relapse, and severity of relapse. RESULTS: Controlling for SUD and psychiatric
      comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV
      across all participants in the left hippocampus (cornu ammonis 1-3, dentate
      gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum,
      and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05;
      uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a
      shorter relapse to use of any drug (P = .048), while CM-related GMV reductions
      predicted severity of substance use relapse (P = .04). CONCLUSIONS AND RELEVANCE:
      Findings indicate that CM was related to decreased GMV in limbic regions, which
      in turn predicted increased risk of relapse in SUD. These results suggest that CM
      may significantly affect the course of SUD treatment outcomes and that SUD
      treatment planning may benefit from identifying and addressing CM.

PMID- 24920453
TI  - Pediatricians manage anaphylaxis poorly regardless of episode severity.
AB  - BACKGROUND: No information exists on how the knowledge or the practice of
      pediatricians regarding anaphylaxis episodes vary with episode severity. The aim
      of this study was to assess and compare pediatrician knowledge on the management
      of mild and severe anaphylaxis using clinical scenarios and to determine factors
      that affect their decisions. METHODS: A questionnaire consisting of eight
      questions on the diagnosis and management of anaphylaxis was distributed at two
      national congresses. A uniform answer box including possible response choices was
      given below each question, and respondents were asked to check the answers that
      they thought appropriate. The management of mild and severe anaphylaxis was
      examined using two clinical case scenarios involving initial treatment,
      monitoring, and discharge recommendations. RESULTS: Four hundred and ten
      questionnaires were analyzed. The percentage of pediatricians who correctly
      answered all questions on the management of mild and severe anaphylaxis scenarios
      was 11.3% and 3.2%, respectively. Pediatricians did significantly better with
      initial treatment, but they were less knowledgeable with respect to observation
      time and discharge criteria in the mild anaphylaxis case scenario compared with
      the severe one (both P < 0.001). Multiple logistic regression analysis identified
      only working in an emergency department or intensive care unit as significantly
      predicting correct diagnosis of anaphylaxis among pediatricians (P = 0.01, 95%
      confidence interval: 0.11-0.57). No pediatrician-related factors predicted
      physician knowledge on the management of anaphylaxis. CONCLUSIONS: Pediatricians
      have difficulty with different steps in managing mild and severe anaphylaxis.
      Their deficiencies in management may result in failure to prevent recurrences of
      mild anaphylaxis and may increase mortality in severe anaphylaxis.

PMID- 24920452
TI  - An Arabidopsis mutant impaired in intracellular calcium elevation is sensitive to
      biotic and abiotic stress.
AB  - BACKGROUND: Ca2+, a versatile intracellular second messenger in various signaling
      pathways, initiates many responses involved in growth, defense and tolerance to
      biotic and abiotic stress. Endogenous and exogenous signals induce cytoplasmic
      Ca2+ ([Ca2+]cyt) elevation, which are responsible for the appropriate downstream
      responses. RESULTS: Here we report on an ethyl-methane sulfonate-mediated
      Arabidopsis mutant that fails to induce [Ca2+]cyt elevation in response to
      exudate preparations from the pathogenic mibrobes Alternaria brassicae,
      Rhizoctonia solani, Phytophthora parasitica var. nicotianae and Agrobacterium
      tumefaciens. The cytoplasmic Ca2+elevation mutant1 (cycam1) is susceptible to
      infections by A. brassicae, its toxin preparation and sensitive to abiotic stress
      such as drought and salt. It accumulates high levels of reactive oxygen species
      and contains elevated salicylic acid, abscisic acid and bioactive jasmonic acid
      iso-leucine levels. Reactive oxygen species- and phytohormone-related genes are
      higher in A. brassicae-treated wild-type and mutant seedlings. Depending on the
      analysed response, the elevated levels of defense-related compounds are either
      caused by the cycam mutation and are promoted by the pathogen, or they are mainly
      due to the pathogen infection or application of pathogen-associated molecular
      patterns. Furthermore, cycam1 shows altered responses to abscisic acid
      treatments: the hormone inhibits germination and growth of the mutant.
      CONCLUSIONS: We isolated an Arabidopsis mutant which fails to induce [Ca2+]cyt
      elevation in response to exudate preparations from various microbes. The higher
      susceptibility of the mutant to pathogen infections correlates with the higher
      accumulation of defense-related compounds, such as phytohormones, reactive oxygen
      species, defense-related mRNA levels and secondary metabolites. Therefore, CYCAM1
      couples [Ca2+]cyt elevation to biotic, abiotic and oxidative stress responses.

PMID- 24920454
TI  - Gender differences in childhood food preference: evaluation using a subjective
      picture choice method.
AB  - BACKGROUND: A preference for calorie-dense food in men seems to be closely linked
      with a considerably higher incidence of obesity in adulthood for men than women,
      but it is not clear in which life stage the gender differences in food preference
      begin to appear. In order to clarify this, a picture choice method has been
      developed that is designed to evaluate food preferences or interests in children
      based on their subjective choices. METHODS: In total, 486 children aged 6-12
      years were enrolled. To evaluate food interest, children were instructed to
      choose any 10 from 36 pictures in the panel showing 10 different foods and 26
      other things. The number of foods chosen was set as the food interest score. For
      food preference, they were also instructed to choose any 10 from 36 pictures in
      the other panel depicting 36 different foods. For the 10 foods chosen, Japanese
      food score, energy density, fat energy content, and saturated fatty acid score
      were calculated. These indices were compared for sex, age group and body mass
      index. RESULTS: Indices reflecting food interest or fat preference were
      significantly higher in boys than girls both in the 7-9- and 10-12-year-old age
      groups. Positive correlations were found between food interest score and energy
      density, fat energy content, and saturated fatty acid score. CONCLUSIONS: Using
      the picture choice method, definite gender differences in food preference were
      identified in early elementary school children. This information could be useful
      for dietary therapy in childhood obesity.

PMID- 24920456
TI  - Violence in the Lives of Rural, Southern, and Poor White Women.
AB  - Poor White single mothers and their children in non-urban communities in the
      American South experience high levels of domestic violence. We report selected
      findings from a life history study among White, low-income, unmarried mothers in
      South Carolina. Here, we examine how domestic violence in both childhood and
      adulthood may inhibit asset development by diminishing low-income single mothers'
      accumulation of human and social capital, thus compromising their well-being as
      adults and parents.

PMID- 24920455
TI  - Global phylogeography of pelagic Polynucleobacter bacteria: restricted geographic
      distribution of subgroups, isolation by distance and influence of climate.
AB  - The free-living planktonic freshwater bacterium Polynucleobacter necessarius
      subspecies asymbioticus (> 99% 16S rRNA similarity) represents a taxon with a
      cosmopolitan distribution and apparently ubiquitous occurrence in lentic
      freshwater habitats. We tested for intra-taxon biogeographic patterns by
      combining cultivation-independent and cultivation methods. A culture collection
      of 204 strains isolated from globally distributed freshwater habitats (Arctic to
      Antarctica) was investigated for phylogeographic patterns based on sequences of
      two markers, the 16S-23S internal transcribed spacers and the glutamine
      synthetase gene (glnA). Genetic distance between isolates showed significant
      geographic distance-decay patterns for both markers, suggesting that an isolation
      by-distance mechanism influences the global phylogeography. Furthermore, a couple
      of subgroups showed restricted geographic distributions. Strains of one subgroup
      were exclusively obtained from tropical sites on four continents (pantropical
      subgroup). Cultivation-independent methods were used to confirm the restricted
      geographic distributions of two subgroups. The pantropical taxon could be
      detected in 63% of investigated tropical habitats but not in any of 121 European
      freshwater samples. Physiological tests indicated that almost all strains of the
      pantropical subgroup failed to grow at temperatures of 4 degrees C, while strains
      affiliated with other subgroups showed good growth at this temperature. This
      suggests that thermal adaptation is involved in phylogeographic structuring of
      the global Polynucleobacter population. 

PMID- 24920458
TI  - Hidden genetic variation evolves with ecological specialization: the genetic
      basis of phenotypic plasticity in Arctic charr ecomorphs.
AB  - The genetic variance that determines phenotypic variation can change across
      environments through developmental plasticity and in turn play a strong role in
      evolution. Induced changes in genotype-phenotype relationships should strongly
      influence adaptation by exposing different sets of heritable variation to
      selection under some conditions, while also hiding variation. Therefore, the
      heritable variation exposed or hidden from selection is likely to differ among
      habitats. We used ecomorphs from two divergent populations of Arctic charr
      (Salvelinus alpinus) to test the prediction that genotype-phenotype relationships
      would change in relation to environment. If present over several generations this
      should lead to divergence in genotype-phenotype relationships under common
      conditions, and to changes in the amount and type of hidden genetic variance that
      can evolve. We performed a common garden experiment whereby two ecomorphs from
      each of two Icelandic lakes were reared under conditions that mimicked benthic
      and limnetic prey to induce responses in craniofacial traits. Using
      microsatellite based genetic maps, we subsequently detected QTL related to these
      craniofacial traits. We found substantial changes in the number and type of QTL
      between diet treatments and evidence that novel diet treatments can in some cases
      provide a higher number of QTL. These findings suggest that selection on
      phenotypic variation, which is both genetically and environmentally determined,
      has shaped the genetic architecture of adaptive divergence in Arctic charr.
      However, while adaptive changes are occurring in the genome there also appears to
      be an accumulation of hidden genetic variation for loci not expressed in the
      contemporary environment. 

PMID- 24920460
TI  - Tertiary montane origin of the Central Asian flora, evidence inferred from cpDNA
      sequences of Atraphaxis (Polygonaceae).
AB  - Atraphaxis has approximately 25 species and a distribution center in Central
      Asia. It has been previously used to hypothesize an origin from montane forest.
      We sampled 18 species covering three sections within the genus and sequenced five
      cpDNA spacers, atpB-rbcL, psbK-psbI, psbA-trnH, rbcL, and trnL-trnF. BEAST was
      used to reconstruct phylogenetic relationship and time divergences, and S-DIVA
      and Lagrange were used, based on distribution area and ecotype data, for
      reconstruction of ancestral areas and events. Our results appear compatible with
      designation of three taxonomic sections within the genus. The generic stem and
      crown ages were Eocene, approximately 47 Ma, and Oligocene 27 Ma, respectively.
      The origin of Atraphaxis is confirmed as montane, with an ancestral area
      consisting of the Junggar Basin and uplands of the Pamir-Tianshan-Alatau-Altai
      mountain chains, and ancestral ecotype of montane forest. Two remarkable
      paleogeographic events, shrinkage of the inland Paratethys Sea at the boundary of
      the late Oligocene and early Miocene, and the time intervals of cooling and
      drying of global climate from 24 (22) Ma onward likely facilitated early
      diversification of Atraphaxis, while rapid uplift of the Tianshan Mountains
      during the late Miocene may have promoted later diversification. 

PMID- 24920457
TI  - Sexual self-schema and depressive symptoms after prostate cancer.
AB  - INTRODUCTION: The years following prostate cancer treatment are characterized by
      changes in sexual functioning and risk for depressive symptoms. Sexual self
      schema (SSS) is a cognitive generalization about sexual aspects of the self that
      are associated with sexual behavior, affect, and the processing of sexually
      relevant information. This study tested if men's SSS moderates the impact of
      sexual morbidity on depressive symptoms. METHODS: Men (N = 66) treated for
      localized prostate cancer in the preceding 2 years were assessed at T1 and 4
      months later (T2). Questionnaires included the Center for Epidemiologic Studies
      Depression Scale, Sexual Self-schema Scale for Men, Sexual Experience Scale, and
      Expanded Prostate Cancer Index Composite. RESULTS: Regressions controlled for
      age, sexual activity, and T1 depressive symptoms revealed no significant effect
      of SSS on depressive symptoms; however, better sexual functioning was related to
      fewer depressive symptoms (B = -0.25, p < 0.05). Results showed significant
      interactions between SSS and sexual outcomes. Among men with high SSS, poor
      sexual functioning was associated with increased depressive symptoms; loss of
      sexual function was particularly distressing. There was no significant effect of
      sexual functioning. Among men with high SSS, there was an inverse relationship
      between sexual engagement and depressive symptoms. Among men with lower SSS,
      greater frequency of sexual behavior was associated with increased depressive
      symptoms. CONCLUSIONS: SSS may be an important individual difference in
      determining the impact of sexual morbidity on psychological adjustment. Men high
      on SSS are more vulnerable to psychological consequences of lower sexual
      functioning and less engagement in sexual activities.

PMID- 24920461
TI  - Future of portable devices for plant pathogen diagnosis.
AB  - The demand for rapid and accurate diagnosis of plant diseases has risen in the
      last decade. On-site diagnosis of single or multiple pathogens using portable
      devices is the first step in this endeavour. Despite extensive attempts to
      develop portable devices for pathogen detection, current technologies are still
      restricted to detecting known pathogens with limited detection accuracy.
      Developing new detection techniques for rapid and accurate detection of multiple
      plant pathogens and their associated variants is essential. Recent single DNA
      sequencing technologies are a promising new avenue for developing future portable
      devices for plant pathogen detection. In this review, we detail the current
      progress in portable devices and technologies used for detecting plant pathogens,
      the current position of emerging sequencing technologies for analysis of plant
      genomics, and the future of portable devices for rapid pathogen diagnosis. 

PMID- 24920462
TI  - Sound production in marbled rockfish (Sebastiscus marmoratus) and implications
      for fisheries.
AB  - Recently, several rockfish species (genus Sebastes) have been reported to be
      soniferous. To determine whether an additional rockfish species produces sounds,
      passive acoustic recordings were analyzed from captive marbled rockfish
      (Sebastiscus marmoratus) during the non-spawning season. Three distinct sounds
      were identified based on frequency features. The common characteristics among all
      sounds were low frequency (below 300 Hz) and rapidly dampened pulses consisting
      of 3-5 acoustic energy cycles. During free-swimming conditions in the canvas
      tank, the fish produced voluntary sounds with lower frequencies than the
      disturbance sounds produced by individuals during prodding. Two types of sounds
      were identified in the disturbance context: one type consists of single or double
      pulses with two peak frequencies, and another type consists of a series of pulses
      with a single peak frequency. These results suggest that specific-species and
      behavior-associated sounds are potentially useful in passive acoustical surveys
      to monitor rockfish populations and distributions remotely. 

PMID- 24920464
TI  - Gro2mat: a package to efficiently read gromacs output in MATLAB.
AB  - Molecular dynamics (MD) simulations are a state-of-the-art computational method
      used to investigate molecular interactions at atomic scale. Interaction processes
      out of experimental reach can be monitored using MD software, such as Gromacs.
      Here, we present the gro2mat package that allows fast and easy access to Gromacs
      output files from Matlab. Gro2mat enables direct parsing of the most common
      Gromacs output formats including the binary xtc-format. No openly available
      Matlab parser currently exists for this format. The xtc reader is orders of
      magnitudes faster than other available pdb/ascii workarounds. Gro2mat is
      especially useful for scientists with an interest in quick prototyping of new
      mathematical and statistical approaches for Gromacs trajectory analyses. (c) 2014
      Wiley Periodicals, Inc. 

PMID- 24920463
TI  - Stem cell dynamics in homeostasis and cancer of the intestine.
AB  - Intestinal stem cells (ISCs) and colorectal cancer (CRC) biology are tightly
      linked in many aspects. It is generally thought that ISCs are the cells of origin
      for a large proportion of CRCs and crucial ISC-associated signalling pathways are
      often affected in CRCs. Moreover, CRCs are thought to retain a cellular hierarchy
      that is reminiscent of the intestinal epithelium. Recent studies offer
      quantitative insights into the dynamics of ISC behaviour that govern homeostasis
      and thereby provide the necessary baseline parameters to begin to apply these
      analyses during the various stages of tumour development. 

PMID- 24920466
TI  - Highly efficient and stable Si nanowires array embedded into transparent polymer
      for visible light photoelectrochemical cell.
AB  - Photoelectrochemical (PEC) cell supports a renewable method for solving current
      environmental and energy issues by combining solar energy collection and
      photocatalysis in a single semiconductor photoelectrode. However, it is still
      challenged by visible light photoelectrodes. The present work reports fabricating
      highly efficient and stable Si nanowires (SiNWs) array as visible light
      photoelectrodes. It involves embedding SiNWs arrays into a transparent polymer
      substrate to build an axial carrier collection geometry. We demonstrated that
      this strategy could significantly strengthen the chemical stability of SiNWs by
      largely reducing their surface area. Moreover, this device structure can also
      enhance visible light absorption efficiency through taking advantage of the
      highly crystalline structure of vapor-liquid-solid (VLS) grown SiNWs. Thus it can
      double the photodegradation ability of SiNWs. 

PMID- 24920465
TI  - Long-term survival of patients with pulmonary arterial hypertension recovering to
      World Health Organization functional class I or II: a historical comparison
      between intravenous epoprostenol and oral agents.
AB  - BACKGROUND: Intravenous epoprostenol is the only drug proved in a randomized
      study to reduce mortality in patients with idiopathic pulmonary arterial
      hypertension (PAH). However, administration of this drug has procedural
      difficulties and a risk of sepsis. Oral drugs provide simple treatment, but their
      benefit for survival has not been proven. A recovery of patients with PAH to
      World Health Organization functional class (WHO-FC) I or II may predict favorable
      survival. METHODS: Survival analyses were performed on a historical cohort of 41
      patients with PAH. The patients were 43 +/- 22 years old, 23 had idiopathic or
      heritable PAH, and 18 had connective tissue disease-associated PAH. The baseline
      was defined as the initial visit to a medical facility. RESULTS: The median
      duration of follow-up was 1276 days (108 to 5389 days) and 21 patients died
      during this period. The estimated survival times for patients who received
      intravenous epoprostenol and did and did not recover to WHO-FC I or II were 4371
      +/- 577 days and 1172 +/- 404 days, respectively. These times for patients who
      were not treated with intravenous epoprostenol and did and did not recover to WHO
      FC I or II were 4717 +/- 554 days and 925 +/- 230 days, respectively. A Cox
      proportional hazard analysis gave a hazard ratio for death after recovery to WHO
      FC I or II of 0.07 (P < 0.001). In contrast, use of intravenous epoprostenol was
      not a significant factor affecting survival (P = 0.96). CONCLUSIONS: Patients
      with PAH who achieve recovery to WHO-FC I or II without use of intravenous
      epoprostenol have similar survival to those who reach the same WHO-FC with use of
      intravenous epoprostenol. Benign survival of patients with PAH who have recovered
      to WHO-FC I or II may extend for several years after onset of the disease.

PMID- 24920467
TI  - Comparison of the effects of clonidine, loperamide and metoclopramide in two
      models of gastric emptying in the rat.
AB  - Several methods are used to evaluate gastric emptying (GE) in rats, which is an
      important endpoint in preclinical drug development. Although phenol red model or
      monitoring of plasma acetaminophen levels are well-established procedures for GE
      assessment, their capacity to detect the effects of pharmacological agents has
      rarely been compared. This study was therefore designed to evaluate clonidine
      with loperamide and metoclopramide in the two test models. Rats were administered
      phenol red or acetaminophen test meals. The remaining amount of phenol red in the
      stomach or the time course of plasma acetaminophen levels was then measured. In
      the phenol red test, loperamide (8 mg/kg, p.o.) and clonidine (100 MUg/kg, s.c.)
      decreased GE (-88 and -42%, P < 0.001 and P < 0.01, respectively). Metoclopramide
      (10 mg/kg, s.c.) accelerated GE (+42%, P < 0.01). Loperamide reduced
      acetaminophen plasma levels (-45% at T15 min, P < 0.05), suggesting a delayed GE.
      Clonidine and metoclopramide increased acetaminophen plasma levels (+115 and
      +152% at T15 min, P < 0.05 and P < 0.001, respectively), suggesting an
      accelerated GE. The three substances did not affect plasma acetaminophen levels
      when acetaminophen was subcutaneously injected, thereby suggesting that
      acetaminophen metabolism/excretion was not modified. Whereas the phenol red test
      allows the evaluation of GE at a single time point, the measurement of plasma
      acetaminophen levels over the time would appear more informative. Nevertheless,
      the fact that clonidine, in contrast to expectation, increased plasma
      acetaminophen levels, suggests that data obtained with the acetaminophen method
      should be interpreted with caution for new chemical entities susceptible to
      modify absorption of acetaminophen from the small intestine. 

PMID- 24920468
TI  - Test implementation of a school-oriented drug prevention program "Study without
      Drugs": pre- and post-testing for effectiveness.
AB  - BACKGROUND: In this article, the test implementation of a school-oriented drug
      prevention program "Study without Drugs" is discussed. The aims of this study
      were to determine the results of the process evaluation and to determine whether
      the proposed school-oriented drug prevention program during a pilot project was
      effective for the participating pupils. METHODS: Sixty second-grade pupils at a
      junior high school in Paramaribo, Suriname participated in the test
      implementation. They were divided into two classes. For the process evaluation
      the students completed a structured questionnaire focusing on content and
      teaching method after every lesson. Lessons were qualified with a score from 0
      10. The process was also evaluated by the teachers through structured interviews.
      Attention was paid to reach, dose delivered, dose received, fidelity, connection,
      achieved effects/observed behaviors, areas for improvement, and lesson strengths.
      The effect evaluation was conducted by using the General Liniair Model (repeated
      measure). The research (-design) was a pre-experimental design with pre-and post
      test. RESULTS: No class or sex differences were detected among the pupils with
      regard to the assessment of content, methodology, and qualification of the
      lessons. Post-testing showed that participating pupils obtained an increased
      knowledge of drugs, their drug-resisting skills were enhanced, and behavior
      determinants (attitude, subjective norm, self-efficacy, and intention) became
      more negative towards drugs. CONCLUSIONS: From the results of the test
      implementation can be cautiously concluded that the program "Study without Drugs"
      may yield positive results when applied in schools). Thus, this pilot program can
      be considered a step towards the development and implementation of an evidence
      based school-oriented program for pupils in Suriname.

PMID- 24920469
TI  - The family assessment device: an update.
AB  - The current study set out to describe family functioning scores of a contemporary
      community sample, using the Family Assessment Device (FAD), and to compare this
      to a currently help-seeking sample. The community sample consisted of 151
      families who completed the FAD. The help-seeking sample consisted of 46 families
      who completed the FAD at their first family therapy appointment as part of their
      standard care at an outpatient family therapy clinic at an urban hospital.
      Findings suggest that FAD means from the contemporary community sample indicate
      satisfaction with family functioning, while FAD scores from the help-seeking
      sample indicate dissatisfaction with family functioning. In addition, the General
      Functioning scale of the FAD continues to correlate highly with all other FAD
      scales, except Behavior Control. The cut-off scores for the FAD indicating
      satisfaction or dissatisfaction by family members with their family functioning
      continue to be relevant and the FAD continues to be a useful tool to assess
      family functioning in both clinical and research contexts. 

PMID- 24920470
TI  - Imatinib mesylate-induced pseudoporphyria in two children.
AB  - Imatinib mesylate was the first of several tyrosine kinase inhibitors approved
      for use in the treatment of a number of human cancers. Adverse cutaneous
      reactions to imatinib are common. Pseudoporphyria has been infrequently reported
      in adults undergoing imatinib therapy for chronic myeloid leukemia. We present
      two children with pseudoporphyria induced by imatinib therapy for hematologic
      malignancies. In view of the burgeoning use of imatinib in children, physicians
      should be aware that pseudoporphyria may develop as a consequence of imatinib
      therapy. 

PMID- 24920471
TI  - Mechanochromic behavior of aryl-substituted buta-1,3-diene derivatives with
      aggregation enhanced emission.
AB  - Three tetra-aryl substituted 1,3-butadiene derivatives with aggregation enhanced
      emission (AEE) and mechanochromic fluorescence behavior have been rationally
      designed and synthesized. The results suggest an effective design strategy for
      developing diverse materials with aggregation induced emission (AIE) and
      significant mechanochromic performance by employing D-pi-A structures with large
      dipole moments. 

PMID- 24920472
TI  - Persistent idiopathic hypoglossal nerve palsy: A motor neuron disease-mimic
      syndrome?

PMID- 24920473
TI  - Nicotine exposure increases the complexity of dopamine neurons in the
      parainterfascicular nucleus (PIF) sub-region of VTA.
AB  - BACKGROUND: Recent publications highlight differences within the sub-regions of
      the ventral tegmental area (VTA) including the parabrachial pigmented nucleus
      (PBP), parainterfascicular nucleus (PIF) and paranigral nucleus (PN) in the
      projections to the prefrontal cortex (PFC) and the glutamatergic pathway.
      METHODS: In order to characterize the effects of prenatal nicotine exposure on
      the mesocorticolimbic system of the rat offspring, local field potentials were
      recorded from 27 sites across the VTA of 9 rats aged 40-55 days. The
      extracellular VTA neural activities were analyzed using Approximate Entropy
      (ApEn) method. Approximate entropy values were then grouped according to each
      anatomic location including the PBP, PIF and PN. RESULTS: Our results have shown
      that the local field potentials corresponding to the neurons located in the PIF
      region of the VTA have ApEn values significantly higher (p = 2x10-4) in the
      maternal nicotine cases when compared to the saline. CONCLUSION: Therefore, we
      speculate that the dopamine neurons located in the PIF sub-region of the VTA are
      very likely involved with the nicotine addiction.

PMID- 24920474
TI  - How collective comparisons emerge without individual comparisons of the options.
AB  - Collective decisions in animal groups emerge from the actions of individuals who
      are unlikely to have global information. Comparative assessment of options can be
      valuable in decision-making. Ant colonies are excellent collective decision
      makers, for example when selecting a new nest-site. Here, we test the dependency
      of this cooperative process on comparisons conducted by individual ants. We
      presented ant colonies with a choice between new nests: one good and one poor.
      Using individually radio-tagged ants and an automated system of doors, we
      manipulated individual-level access to information: ants visiting the good nest
      were barred from visiting the poor one and vice versa. Thus, no ant could
      individually compare the available options. Despite this, colonies still
      emigrated quickly and accurately when comparisons were prevented. Individual
      level rules facilitated this behavioural robustness: ants allowed to experience
      only the poor nest subsequently searched more. Intriguingly, some ants appeared
      particularly discriminating across emigrations under both treatments, suggesting
      they had stable, high nest acceptance thresholds. Overall, our results show how a
      colony of ants, as a cognitive entity, can compare two options that are not both
      accessible by any individual ant. Our findings illustrate a collective decision
      process that is robust to differences in individual access to information. 

PMID- 24920475
TI  - From 'third pole' to north pole: a Himalayan origin for the arctic fox.
AB  - The 'third pole' of the world is a fitting metaphor for the Himalayan-Tibetan
      Plateau, in allusion to its vast frozen terrain, rivalling the Arctic and
      Antarctic, at high altitude but low latitude. Living Tibetan and arctic mammals
      share adaptations to freezing temperatures such as long and thick winter fur in
      arctic muskox and Tibetan yak, and for carnivorans, a more predatory niche. Here,
      we report, to our knowledge, the first evolutionary link between an Early
      Pliocene (3.60-5.08 Myr ago) fox, Vulpes qiuzhudingi new species, from the
      Himalaya (Zanda Basin) and Kunlun Mountain (Kunlun Pass Basin) and the modern
      arctic fox Vulpes lagopus in the polar region. A highly hypercarnivorous
      dentition of the new fox bears a striking resemblance to that of V. lagopus and
      substantially predates the previous oldest records of the arctic fox by 3-4 Myr.
      The low latitude, high-altitude Tibetan Plateau is separated from the nearest
      modern arctic fox geographical range by at least 2000 km. The apparent connection
      between an ancestral high-elevation species and its modern polar descendant is
      consistent with our 'Out-of-Tibet' hypothesis postulating that high-altitude
      Tibet was a training ground for cold-environment adaptations well before the
      start of the Ice Age. 

PMID- 24920476
TI  - Of babies and birds: complex tool behaviours are not sufficient for the evolution
      of the ability to create a novel causal intervention.
AB  - Humans are capable of simply observing a correlation between cause and effect,
      and then producing a novel behavioural pattern in order to recreate the same
      outcome. However, it is unclear how the ability to create such causal
      interventions evolved. Here, we show that while 24-month-old children can produce
      an effective, novel action after observing a correlation, tool-making New
      Caledonian crows cannot. These results suggest that complex tool behaviours are
      not sufficient for the evolution of this ability, and that causal interventions
      can be cognitively and evolutionarily disassociated from other types of causal
      understanding. 

PMID- 24920478
TI  - Intraspecific phenotypic variation among alewife populations drives parallel
      phenotypic shifts in bluegill.
AB  - Evolutionary diversification within consumer species may generate selection on
      local ecological communities, affecting prey community structure. However, the
      extent to which this niche construction can propagate across food webs and shape
      trait variation in competing species is unknown. Here, we tested whether niche
      construction by different life-history variants of the planktivorous fish alewife
      (Alosa pseudoharengus) can drive phenotypic divergence and resource use in the
      competing species bluegill (Lepomis macrochirus). Using a combination of common
      garden experiments and a comparative field study, we found that bluegill from
      landlocked alewife lakes grew relatively better when fed small than large
      zooplankton, had gill rakers better adapted for feeding on small-bodied prey and
      selected smaller zooplankton compared with bluegill from lakes with anadromous or
      no alewife. Observed shifts in bluegill foraging traits in lakes with landlocked
      alewife parallel those in alewife, suggesting interspecific competition leading
      to parallel phenotypic changes rather than to divergence (which is commonly
      predicted). Our findings suggest that species may be locally adapted to prey
      communities structured by different life-history variants of a competing dominant
      species.

PMID- 24920477
TI  - Demographic consequences of heavy metals and persistent organic pollutants in a
      vulnerable long-lived bird, the wandering albatross.
AB  - Seabirds are top predators of the marine environment that accumulate contaminants
      over a long life-span. Chronic exposure to pollutants is thought to compromise
      survival rate and long-term reproductive outputs in these long-lived organisms,
      thus inducing population decline. However, the demographic consequences of
      contaminant exposure are largely theoretical because of the dearth of long-term
      datasets. This study aims to test whether adult survival rate, return to the
      colony and long-term breeding performance were related to blood mercury (Hg),
      cadmium (Cd) and persistent organic pollutants (POPs), by using a capture-mark
      recapture dataset on the vulnerable wandering albatross Diomedea exulans. We did
      not find evidence for any effect of contaminants on adult survival probability.
      However, blood Hg and POPs negatively impacted long-term breeding probability,
      hatching and fledging probabilities. The proximate mechanisms underlying these
      deleterious effects are likely multifaceted, through physiological perturbations
      and interactions with reproductive costs. Using matrix population models, we
      projected a demographic decline in response to an increase in Hg or POPs
      concentrations. This decline in population growth rate could be exacerbated by
      other anthropogenic perturbations, such as climate change, disease and fishery
      bycatch. This study gives a new dimension to the overall picture of environmental
      threats to wildlife populations. 

PMID- 24920479
TI  - Trophic divergence despite morphological convergence in a continental radiation
      of snakes.
AB  - Ecological and phenotypic convergence is a potential outcome of adaptive
      radiation in response to ecological opportunity. However, a number of factors may
      limit convergence during evolutionary radiations, including interregional
      differences in biogeographic history and clade-specific constraints on form and
      function. Here, we demonstrate that a single clade of terrestrial snakes from
      Australia--the oxyuranine elapids--exhibits widespread morphological convergence
      with a phylogenetically diverse and distantly related assemblage of snakes from
      North America. Australian elapids have evolved nearly the full spectrum of
      phenotypic modalities that occurs among North American snakes. Much of the
      convergence appears to involve the recurrent evolution of stereotyped
      morphologies associated with foraging mode, locomotion and habitat use. By
      contrast, analysis of snake diets indicates striking divergence in feeding
      ecology between these faunas, partially reflecting regional differences in
      ecological allometry between Australia and North America. Widespread phenotypic
      convergence with the North American snake fauna coupled with divergence in
      feeding ecology are clear examples of how independent continental radiations may
      converge along some ecological axes yet differ profoundly along others.

PMID- 24920481
TI  - King penguin demography since the last glaciation inferred from genome-wide data.
AB  - How natural climate cycles, such as past glacial/interglacial patterns, have
      shaped species distributions at the high-latitude regions of the Southern
      Hemisphere is still largely unclear. Here, we show how the post-glacial warming
      following the Last Glacial Maximum (ca 18 000 years ago), allowed the
      (re)colonization of the fragmented sub-Antarctic habitat by an upper-level marine
      predator, the king penguin Aptenodytes patagonicus. Using restriction site
      associated DNA sequencing and standard mitochondrial data, we tested the
      behaviour of subsets of anonymous nuclear loci in inferring past demography
      through coalescent-based and allele frequency spectrum analyses. Our results show
      that the king penguin population breeding on Crozet archipelago steeply increased
      in size, closely following the Holocene warming recorded in the Epica Dome C ice
      core. The following population growth can be explained by a threshold model in
      which the ecological requirements of this species (year-round ice-free habitat
      for breeding and access to a major source of food such as the Antarctic Polar
      Front) were met on Crozet soon after the Pleistocene/Holocene climatic
      transition. 

PMID- 24920482
TI  - Discovery of protein disulfide isomerase P5 inhibitors that reduce the secretion
      of MICA from cancer cells.
AB  - In order to regulate the activity of P5, which is a member of the protein
      disulfide isomerase family, we screened a chemical compound library for P5
      specific inhibitors, and identified two candidate compounds (anacardic acid and
      NSC74859). Interestingly, anacardic acid inhibited the reductase activity of P5,
      but did not inhibit the activity of protein disulfide isomerase (PDI), thiol
      disulfide oxidoreductase ERp57, or thioredoxin. NSC74859 inhibited all these
      enzymes. When we examined the effects of these compounds on the secretion of
      soluble major histocompatibility complex class-I-related gene A (MICA) from
      cancer cells, anacardic acid was found to decrease secretion. In addition,
      anacardic acid was found to reduce the concentration of glutathione up-regulated
      by the anticancer drug 17-demethoxygeldanamycin in cancer cells. These results
      suggest that anacardic acid can both inhibit P5 reductase activity and decrease
      the secretion of soluble MICA from cancer cells. It might be a novel and potent
      anticancer treatment by targeting P5 on the surface of cancer cells. 

PMID- 24920483
TI  - Head and neck cancer recurrence: a prospective analysis of 401 follow-up visits
      to an Australian cancer centre.

PMID- 24920484
TI  - Development and performance evaluation of an ultralow flow nanoliquid
      chromatography-tandem mass spectrometry set-up.
AB  - LC-MS/MS is the most commonly used technique for the identification and
      characterization of proteins. The efficiency of the electrospray process is a
      critical factor in LC-MS/MS. Despite the benefits associated with very low flow
      rates for the ionization efficiency, most LC-MS/MS platforms are operated at
      relatively high flow rates. The purpose of this work was to develop a nano LC
      system operable at a flow rate of 20 nL/min, applicable for routine analysis in
      proteomics laboratories. Peptide separation was performed with an analytical
      column packed with 2 MUm porous chromatographic beads, a length of 25 cm and an
      inner diameter (i.d.) of 25 MUm. Practical usability, reproducibility, and
      overall performance of the system were evaluated with a tryptic peptide mixture
      generated from HeLa cells. Using 100 ng of sample, we identified on average 3721
      protein groups based on 25,699 peptides. We demonstrate that the number of
      peptides identified with this system increases with decreasing flow rates.
      Probing the sensitivity of the set-up we analyzed only 10 ng of the sample,
      identifying an average number of 2042 protein groups based on 11 424 peptides.
      All MS data have been deposited in the ProteomeXchange with identifier PXD000396
      (http://proteomecentral.proteomexchange.org/dataset/PXD000396).

PMID- 24920485
TI  - Photoresponsive superhydrophobic coating for regulating boundary slippage.
AB  - A photoresponsive copolymer containing catechol and azobenzene derivatives was
      synthesized. The copolymer easily attached onto various substrates and showed a
      photoresponsive characteristic because of its catechol and azobenzene functional
      groups. The copolymer was successfully assembled on nanoparticles, plate mica,
      and rough anodized aluminum surface. The rough anodized aluminum sheet retained
      the Cassie-Baxter state after being modified with the copolymer. Moreover,
      surface adhesion can be interchanged by changing the UV exposure time. The
      sliding and adhesive states of water droplets were achieved by UV exposure and
      dark storage. Boundary slip on the rough sheet was measured using a commercial
      rheometer, and interchangeable slip length was also obtained after irradiation or
      storage. The versatile, substrate-independent approach may be significant in the
      development of new materials for smart fluid devices. 

PMID- 24920480
TI  - Comparative genomics of the mimicry switch in Papilio dardanus.
AB  - The African Mocker Swallowtail, Papilio dardanus, is a textbook example in
      evolutionary genetics. Classical breeding experiments have shown that wing
      pattern variation in this polymorphic Batesian mimic is determined by the
      polyallelic H locus that controls a set of distinct mimetic phenotypes. Using
      bacterial artificial chromosome (BAC) sequencing, recombination analyses and
      comparative genomics, we show that H co-segregates with an interval of less than
      500 kb that is collinear with two other Lepidoptera genomes and contains 24
      genes, including the transcription factor genes engrailed (en) and invected
      (inv). H is located in a region of conserved gene order, which argues against any
      role for genomic translocations in the evolution of a hypothesized multi-gene
      mimicry locus. Natural populations of P. dardanus show significant associations
      of specific morphs with single nucleotide polymorphisms (SNPs), centred on en. In
      addition, SNP variation in the H region reveals evidence of non-neutral molecular
      evolution in the en gene alone. We find evidence for a duplication potentially
      driving physical constraints on recombination in the lamborni morph. Absence of
      perfect linkage disequilibrium between different genes in the other morphs
      suggests that H is limited to nucleotide positions in the regulatory and coding
      regions of en. Our results therefore support the hypothesis that a single gene
      underlies wing pattern variation in P. dardanus. 

PMID- 24920486
TI  - Concise and broadly applicable method for determining the genomic sequences of
      North-American-type porcine reproductive and respiratory syndrome viruses in
      various clusters.
AB  - We developed a concise and broadly applicable method for accurate genomic
      sequencing of North American genotype (NA-type) porcine reproductive and
      respiratory syndrome viruses (PRRSVs) that overcomes high genetic variability of
      the viruses. The method, designated "combination of consensus oligonucleotide
      reverse transcription and multiple displacement amplification" (CORT-MDA),
      involves reverse-transcription of viral RNA followed by shotgun sequencing after
      amplification using only 11 degenerate oligonucleotide primers; these primers
      were designed against consensus regions within the open reading frames of the 124
      NA-type PRRSV strains with reported full-length genomic sequences. Sequencing of
      the 192 shotgun clones generated per virus showed 80% to 94% coverage on the
      reported PRRSV genomic sequence, such that only 2 or 3 unread regions had to be
      resequenced after PCR amplification using custom primers. Direct sequencing of RT
      PCR products confirmed absolute consistency between sequences determined by the
      CORT-MDA method and those from RT-PCR. These results suggest that our method is
      applicable to diverse NA-type viruses. 

PMID- 24920487
TI  - Molecular characterization of enterohemorrhagic Escherichia coli isolates from
      cattle.
AB  - A total of 21 (4.3%) enterohemorrhagic E. coli strains were isolated by
      biochemical tests and identification of the eae(+)stx1(+)stx2(+) genotype from
      490 stool samples obtained from calves with diarrhea during 1-year period from a
      major farm in Tehran, Iran. All of the strains showed resistance to ampicillin,
      ciprofloxacin, trimethoprim, streptomycin, chloramphenicol and tetracycline,
      while 19% showed resistance to gentamicin. Out of 21 EHEC strains, 11 (53%)
      harbored class 1 integron. Two different amplification products, which were
      approximately 750 and 1,700 bp in size, were obtained from amplified variable
      regions (in-F/in-R primers) in 3 (14.3%) and 4 (19%) of the EHEC isolates, which
      corresponded to dfrA7(dihydrofolate reductase type I) and
      dfrA1/aadA1(dihydrofolate reductase/aminoglycoside adenyltransferase) resistance
      gene cassettes, respectively, and this was confirmed by sequencing. Genotyping
      analysis revealed a total of 16 pulsotypes that corresponded to 16 isolates with
      the similarity indices of 62% and 30% for the most and least similar isolates,
      respectively, 9 of which harbored class 1 integron. Analysis of pulsotypes showed
      an extensive diversity among the isolates harboring integron, which is indicative
      of a lack of any significant genetic relatedness among the isolates. No obvious
      relation could be deduced between integron content and special pulsotypes. The
      little data available on the genotyping patterns of EHEC isolates from cattle and
      their resistance gene contents emphasize the need to establish genotyping
      databases in order to monitor and source track the source of emergence and spread
      of new resistant and integron-carrying genotypes. 

PMID- 24920488
TI  - CD7 promotes extramedullary involvement of the B-cell acute lymphoblastic
      leukemia line Tanoue by enhancing integrin beta2-dependent cell adhesiveness.
AB  - Extramedullary involvement (EMI) is a factor that defines prognosis of acute
      lymphoblastic leukemia; however, the molecular mechanism(s) remain elusive. Here,
      we show that CD7 promotes EMI of the human B-cell acute lymphoblastic leukemia
      cell line Tanoue. The Tanoue cell line expressing firefly luciferase, Luc-Tanoue,
      was transplanted into non-obese diabetic/severe combined immunodeficient mice,
      and cells infiltrated into the brain were cultured ex vivo. This process was
      repeated 4 times to obtain the highly invasive line Luc-Tanoue-F4. Comparison of
      the global gene expression signatures of Luc-Tanoue-F4 and Luc-Tanoue indicated
      that the CD7 gene showed the largest increase in expression among EMI-related
      genes in Luc-Tanoue-F4 cells. Overexpression of CD7 in Tanoue enhanced cell
      invasiveness. Among cell migration, proliferation, adhesion and protease
      activity, only cell adhesiveness showed enhancement in Luc-Tanoue-F4. Expression
      of the intracellular domain, but not the extracellular domain, of CD7 enhanced
      cell adhesiveness. Luc-Tanoue-F4 showed a higher level of integrin beta2
      expression; overexpression of CD7 induced the expression of integrin beta2 in Luc
      Tanoue. These results show that CD7 induces integrin beta2 and enhances cell
      adhesiveness and invasiveness in Tanoue cells. This study highlights the role of
      the CD7/integrin beta2 axis as a critical pathway in the process of EMI of human
      B-cell acute lymphoblastic leukemia.

PMID- 24920489
TI  - House dust-mite allergen exposure is associated with serum specific IgE but not
      with respiratory outcomes.
AB  - Exposure to house dust has been associated with asthma in adults, and this is
      commonly interpreted as a direct immunologic response to dust-mite allergens in
      those who are IgE sensitized to house dust-mite. Mattress house dust-mite
      concentrations were measured in a population-based sample of 2890 adults aged
      between 27 and 56 years living in 22 centers in 10 countries. Generalized linear
      mixed models were employed to explore the association of respiratory symptoms
      with house dust-mite concentrations, adjusting for individual and household
      confounders. There was no overall association of respiratory outcomes with
      measured house dust-mite concentrations, even in those who reported they had
      symptoms on exposure to dust and those who had physician-diagnosed asthma.
      However, there was a positive association of high serum specific IgE levels to
      HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative
      association of sensitization to cat with increasing house dust-mite
      concentrations. In conclusion, there was no evidence that respiratory symptoms in
      adults were associated with exposure to house dust-mite allergen in the mattress,
      but an association of house mite with strong sensitization was observed. 

PMID- 24920490
TI  - Age, period, and cohort effects in perinatal epidemiology: implications and
      considerations.

PMID- 24920491
TI  - Determination of the electronic energy levels of colloidal nanocrystals using
      field-effect transistors and Ab-initio calculations.
AB  - Colloidal nanocrystals electronic energy levels are determined by strong size
      dependent quantum confinement. Understanding the configuration of the energy
      levels of nanocrystal superlattices is vital in order to use them in
      heterostructures with other materials. A powerful method is reported to determine
      the energy levels of PbS nanocrystal assemblies by combining the utilization of
      electric-double-layer-gated transistors and advanced ab-initio theory. 

PMID- 24920492
TI  - Cerebral microbleeds in patients with Parkinson's disease.
AB  - Cerebral microbleeds (CMBs) are known to be associated with cognitive impairments
      in the elderly and in patients with various diseases; however, the nature of this
      association has not yet been evaluated in Parkinson's disease (PD). In the
      present study, we analyzed the incidence of CMBs in PD according to cognitive
      status, and the impact of CMBs on cognitive performance was also evaluated. The
      CMBs in PD with dementia (n = 36), mild cognitive impairment (MCI, n = 46), or
      cognitively normal (n = 41) were analyzed using conventional T2*-weighted
      gradient-recalled echo images. Additionally, the relationship between the
      presence of CMBs and cognitive performance on individual tests of cognitive
      subdomains was analyzed using a detailed neuropsychological test. CMBs occurred
      more frequently in PD patients with dementia (36.1 %) compared to those with MCI
      (15.2 %), those who are cognitively normal (14.6 %), and normal controls (12.2 %,
      p = 0.025). However, the significant association of CMBs with PD dementia
      disappeared after adjusting white matter hyperintensities (WMHs) as a covariate.
      The frequencies of deep, lobar, and infratentorial CMBs did not differ among the
      four groups. After adjusting for age, sex, years of education, and WMHs, PD
      patients with CMBs had poorer performance in attention domain compared with those
      without CMBs (34.9 vs 42.6, p = 0.018). The present data demonstrate that even
      though CMBs were inseparably associated with the presence of WMHs, CMBs occur
      more commonly in PD patients with dementia than in those without dementia.
      Additionally, the burden of CMBs may contribute to further cognitive impairment
      in PD.

PMID- 24920493
TI  - Relapse of tardive dystonia after globus pallidus deep-brain stimulation
      discontinuation.

PMID- 24920494
TI  - Dietary educational interventions for management of hyperphosphatemia in
      hemodialysis patients: a systematic review and meta-analysis.
AB  - Strategies to enhance knowledge of and adherence to dietary guidelines for
      management of hyperphosphatemia in hemodialysis patients have been studied
      extensively over the past decade. This review is the first to compile all of them
      (2003-2013) and conduct a meta-analysis through calculation of effect size, with
      the aim of identifying the optimal nutrition education methods for effective
      management of hyperphosphatemia in hemodialysis patients. The following
      strategies were identified as being effective in changing dietary behavior: 1)
      use of self-evaluation and self-regulation techniques within educational tools,
      along with easy-to-apply skills; 2) individualized counseling by a renal
      dietitian provided just before the hemodialysis session; 3) high-intensity
      education; and 4) long duration of interventions. Future studies should focus on
      conducting randomized controlled trials with powered samples to help generate
      stronger evidence. 

PMID- 24920495
TI  - Characterization of chemical constituents and rats metabolites of Shuanghua Baihe
      tablets by HPLC-Q-TOF-MS/MS.
AB  - A high-performance liquid chromatography/quadrupole time-of-flight mass
      spectrometry method was established to detect as many constituents in rat
      biological fluids as possible after oral administration of Shuanghua Baihe
      tablets (SBT). An Agilent Poroshell 120 EC-C18 column was adopted to separate the
      samples, and mass spectra were acquired in positive and negative modes. First,
      the fingerprints of SBT were established, resulting in 32 components being
      detected within 40 min. Among these compounds, 12 were tentatively identified by
      comparing the retention times and mass spectral data with those of reference
      standards and the reference literature; the other 20 components were tentatively
      assigned solely based on the MS data. Furthermore, metabolites in rat plasma and
      urine after oral administration of SBT were also analyzed. A total of 19
      compounds were identified, including 13 prototypes and six metabolites through
      metabolic pathways of demethylation and glucuronide conjugation. Glucuronidated
      alkaloids were the main constituents in the plasma, and were then excreted from
      urine. This is the first systematic study on the metabolic profiling of SBT.

PMID- 24920496
TI  - Nucleation and growth mechanisms of hcp domains in compressed iron.
AB  - In our previous work, we have pointed out that the shock-induced phase transition
      in iron occurs with the help of interface energy which reduces the potential
      barrier between two phases. Here, through studying the nucleation and growth
      mechanisms of hcp domains in compressed iron, we find that the flatted-octahedral
      structure (FOS) is the primary structural unit of the embryo nucleus and phase
      interface of hcp domains, and the interfacial energy is reduced via formation of
      FOSs. The phase transition process can be described by the following four stages:
      (i) Some atoms deviate from their equilibrium positions with the aid of thermal
      fluctuations to form FOSs with two different deformation directions in the local
      region; (ii) FOSs with different deformation directions aggregate to form a thin
      stratified structure like twin-crystal configuration; (iii) The thin stratified
      structure undergoes a relative slip to form the new hcp phase; (iv) The hcp phase
      domain grows up through the formation of new FOSs along the phase boundary. In
      addition, through comparing the time evolution curves of initial single phase
      domain, we find that the growth rate of single phase domain depends on the
      loading way and its occurrence time. 

PMID- 24920498
TI  - How does heart rate recovery after sub-maximal exercise correlate with maximal
      exercise testing in children with CF?
AB  - BACKGROUND: Disease progression in cystic fibrosis (CF) is marked by worsening
      exercise tolerance. Further, maximal exercise capacity (VO2 peak) correlates with
      survival in CF, but maximal tests are uncomfortable and resource-intensive. A
      three-minute step test (STEP) has been validated in CF. Heart rate (HR) recovery
      after exercise correlates with all-cause mortality in adult non-CF populations.
      We compared HR recovery after the three-minute step test with VO2 peak in
      children with CF. METHODS: Twenty-four children with CF performed STEP and a
      maximal exercise test. Correlation between the tests was assessed. RESULTS:
      Maximum HR on STEP was lower than on the maximal test (140 vs. 190, p<0.01). Peak
      HR during STEP correlated inversely with VO2 peak. In subjects with mild lung
      disease, faster HR recovery after STEP correlated with higher VO2 peak.
      CONCLUSIONS: The three-minute step test is a feasible submaximal test in this
      patient population. HR during and after a three-minute step test may reflect VO2
      peak in children with CF.

PMID- 24920497
TI  - Meconium ileus in cystic fibrosis is not linked to central repetitive region
      length variation in MUC1, MUC2, and MUC5AC.
AB  - BACKGROUND: Mucins are excellent candidates for contributing to the presence of
      meconium ileus (MI) in cystic fibrosis (CF) due to their extensive genetic
      variation and known function in intestinal physiology. The length of variants in
      mucin central repetitive regions has not been explored as "risk" factors for MI
      in CF. METHODS: We investigated the length polymorphisms in the central
      repetitive regions of MUC1, MUC2, and MUC5AC by Southern blot and tested for
      association with MI in CF subjects. RESULTS: No significant associations were
      found for the allele sizes of any of the genes with respect to the prevalence of
      MI (p values=0.33, 0.16, and 0.71 for MUC1, MUC2, and MUC5AC, respectively).
      CONCLUSIONS: The genetic length variants in the central repetitive region of
      three MUC genes studied are not associated with MI in subjects with CF.

PMID- 24920499
TI  - The dineolignan from Saururus chinensis, manassantin B, inhibits tumor-induced
      angiogenesis via downregulation of matrix metalloproteinases 9 in human
      endothelial cells.
AB  - Manassantin B (MB) is a neolignan isolated from Saururus chinensis that exhibits
      a range of activities, including anti-inflammatory, antiseptic and antitumor
      activity. MB was recently found to affect cell adhesion and expression of several
      adhesion molecules. Based on the important roles of these adhesion molecules in
      angiogenesis, we evaluated a possible role for MB in tumor-induced angiogenesis
      in endothelial cells (ECs). In the present study, we found that MB blocked tumor
      induced tube formation of ECs and significantly inhibited the invasion of ECs
      through the reconstituted basement membrane. MB suppressed the activity of matrix
      metalloproteinases (MMPs) and downregulated the expression of matrix
      metalloproteinases 9. Western blotting showed reduction of RUNX2 activation by
      MB. RUNX2 transcription factor assay and chromatin immunoprecipitation assay
      showed that the interaction between RUNX2 and target sequences in the matrix
      metalloproteinases 9 promoters was inhibited by MB. Our findings suggested that
      the inhibitory effects of MB on tumor-induced angiogenesis were caused by matrix
      metalloproteinases 9 inhibition, which was associated with the downregulation of
      RUNX2 transcriptional activity.

PMID- 24920500
TI  - Correction: High-order social interactions in groups of mice.

PMID- 24920502
TI  - Share of mass transit miles traveled and reduced motor vehicle fatalities in
      major cities of the United States.
AB  - The USA leads the developed world in motor vehicle fatalities, presenting a
      critical public health threat. We examined whether an increasing share of mass
      transit use, relative to vehicle miles traveled on public roads, was associated
      with reduced motor vehicle fatalities. We used annual city-level data for the USA
      from 1982-2010 provided by the Fatality Accident Reporting System, the Texas A&M
      Transportation Institute, the Census Bureau, and the National Oceanic and
      Atmospheric Administration to estimate a structural equation model of the factors
      associated with mass transit miles and motor vehicle fatalities. The final
      analytic data included 2,900 observations from 100 cities over 29 years. After
      accounting for climate, year, and the economic costs of driving, an increasing
      share of mass transit miles traveled per capita was associated with reduced motor
      vehicle fatalities. The costs of congestion to the average commuter and gas
      prices were positively associated with increasing the share of mass transit miles
      traveled. The economic costs of driving increased over time, while both the
      fatality rate and the share of mass transit miles traveled decreased over time.
      Increasing the share of mass transit miles traveled may be associated with fewer
      motor vehicle miles traveled. Increasing mass transit uptake may be an effective
      public health intervention to reduce motor vehicle fatalities in cities. 

PMID- 24920504
TI  - [Dance projects as an integral part of CI rehabilitation and their impact on
      mental health: a pilot study].
AB  - BACKGROUND: Alongside improvements in hearing and communication skills, the
      rehabilitation of children, adolescents and adults with a cochlear implant (CI)
      in recent years has increasingly taken into account mental health and quality of
      life issues. In the context of the programs offered, this study assesses the
      significance of dance for the mental health of adult clients with a CI. METHODS:
      Eleven adult CI users participated in a dance project, which took place as a
      cooperation between the ENT University Hospital Heidelberg and the Baden State
      Theatre Karlsruhe. Participants were questioned at two different time points for
      assessment with the mental health scales (SPG). These scales measure seven
      different aspects of psychosocial well-being (including autonomy, willpower,
      affirmation of life and meaningfulness). RESULTS: Significant positive changes in
      the domains of affirmation of life, self-reflection and social integration were
      revealed by before and after comparisons; tendencies toward positive change were
      observed (p <= 0.10) in the domains of willpower, naturalness and meaningfulness.
      No changes were observed in the autonomy domain. CONCLUSION: The results indicate
      that the mental health of adult clients with a CI can be strengthened by dance as
      a complementary rehabilitation module. Concepts of CI rehabilitation should
      increasingly find anchor in the consideration of such arrangements for its range
      of offers.

PMID- 24920503
TI  - [Personalized molecular medicine: new paradigms in the treatment of cochlear
      implant and cancer patients].
AB  - OBJECTIVES: To evaluate present options for the indication of cochlear implants
      (CI) and new forms of treatment for head and neck cancer, melanomas and basal
      cell carcinomas, with emphasis on future perspectives. METHODS: A literature
      search was performed in the PubMed database. Search parameters were "personalized
      medicine", "individualized medicine" and "molecular medicine". RESULTS:
      Personalized medicine based on molecular-genetic evaluation of functional
      proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming
      increasingly important for the indication of CI in the context of infant
      deafness. Determination of HER2/EGFR mutations in the epithelial growth factor
      receptor (EGFR) gene may be an important prognostic parameter for therapeutic
      decisions in head and neck cancer patients. In basal cell carcinoma therapy,
      mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly
      influence the indication of therapeutic Hedgehog inhibition, e.g. using small
      molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required
      for specific molecular therapy of metastasizing melanomas. The significant
      advances in the field of specific molecular therapy are best illustrated by the
      availability of the first gene therapeutic procedures for treatment of RPE65
      induced infantile retinal degradation. CONCLUSION: The aim of personalized
      molecular medicine is to identify patients who will respond particularly
      positively or negatively (e.g. in terms of adverse side effects) to a therapy
      using the methods of molecular medicine. This should allow a specific therapy to
      be successfully applied or preclude its indication in order to avoid serious
      adverse side effects. This approach serves to stratify patients for adequate
      treatment.

PMID- 24920501
TI  - Quantitative proteomics in cardiovascular research: global and targeted
      strategies.
AB  - Extensive technical advances in the past decade have substantially expanded
      quantitative proteomics in cardiovascular research. This has great promise for
      elucidating the mechanisms of cardiovascular diseases and the discovery of
      cardiac biomarkers used for diagnosis and treatment evaluation. Global and
      targeted proteomics are the two major avenues of quantitative proteomics. While
      global approaches enable unbiased discovery of altered proteins via relative
      quantification at the proteome level, targeted techniques provide higher
      sensitivity and accuracy, and are capable of multiplexed absolute quantification
      in numerous clinical/biological samples. While promising, technical challenges
      need to be overcome to enable full utilization of these techniques in
      cardiovascular medicine. Here, we discuss recent advances in quantitative
      proteomics and summarize applications in cardiovascular research with an emphasis
      on biomarker discovery and elucidating molecular mechanisms of disease. We
      propose the integration of global and targeted strategies as a high-throughput
      pipeline for cardiovascular proteomics. Targeted approaches enable rapid,
      extensive validation of biomarker candidates discovered by global proteomics.
      These approaches provide a promising alternative to immunoassays and other low
      throughput means currently used for limited validation. 

PMID- 24920505
TI  - Maternal aspects of fetal cardiac intervention.
AB  - OBJECTIVES: Fetal cardiac interventions have the potential to alter natural
      disease progression and reduce morbidity and mortality in children. Although
      there are already encouraging data on fetal outcome, information on maternal
      morbidity and mortality after intervention is scarce. The aim of the present
      study was to assess maternal aspects, pregnancy-associated risks and adverse
      events in 53 intrauterine cardiac interventions. METHODS: Between October 2000
      and December 2012, 53 fetal cardiac interventions were performed in 47 patients
      (43 aortic valve dilations in 39 patients, seven pulmonary valve dilations in six
      patients and three balloon atrioseptostomies in two patients). Median gestational
      age was 26 + 4 (range, 20 + 3 to 33 + 1) weeks. Interventions were performed by
      an ultrasound-guided percutaneous approach under general anesthesia. All medical
      records and patient charts were analyzed retrospectively. RESULTS: All women were
      considered to be healthy in the preoperative assessment; 39 (83%) patients
      continued pregnancy until term and eight of 47 patients had an intrauterine fetal
      death (IUFD) and were induced. Postoperative nausea was reported in 29.8% of
      patients and abdominal pain in 36.2% of patients on the day of surgery. Preterm
      contractions were observed in two patients; no preterm prelabor rupture of
      membranes occurred. One severe postpartum hemorrhage was observed in a patient
      with IUFD and subsequent induction; however, this was unrelated to the balloon
      valvuloplasty. No intensive care unit admission and no major anesthesia
      associated complications (aspiration, anaphylactic reaction, cardiovascular
      collapse, damage to teeth, laryngeal damage, awareness or hypoxic brain damage)
      were observed. Maternal mortality was zero. A significant learning curve was
      observed in terms of duration of intervention. CONCLUSION: In our experience,
      percutaneous needle-guided fetal cardiac intervention seems to be a safe
      procedure for the mother. In 53 procedures no major maternal complication
      directly related to the intervention was observed.

PMID- 24920506
TI  - Ultrafast Cr(VI) removal from polluted water by microwave synthesized iron oxide
      submicron wires.
AB  - Iron oxide submicron wires are successfully synthesized via a microwave
      irradiation method within a short period of 20 s. Upon reduction, this material
      shows orders of magnitude faster Cr(VI) removal rate than conventional
      adsorbents. A redox reaction based removal mechanism is revealed instead of
      adsorption.

PMID- 24920507
TI  - Chorioamniontis in preterm delivery is associated with degradation of decorin and
      biglycan and depletion of hyaluronan in fetal membranes.
AB  - OBJECTIVE: The proteoglycan decorin stabilizes collagen whereas biglycan and
      hyaluronan disrupt well-organized collagen. The aim was to determine the
      concentrations of these constituents in fetal membranes in relation to
      gestational age, preterm labour, PPROM and chorioamnionitis. STUDY DESIGN:
      Preterm fetal membranes (24-34 weeks gestation) were obtained from elective
      caesarean deliveries (N = 4), from PPROM (N = 14), and from preterm labour (N =
      14). Term fetal membranes from elective caesarean deliveries (N = 9) and
      spontaneous vaginal deliveries (N = 11) were used for comparison.
      Chorioamnionitis was assessed histologically. The proteoglycans were analysed
      using alcian blue precipitation, SDS-PAGE and immunostaining. Hyaluronan was
      estimated by a radioimmunoassay. RESULTS: Preterm amniotic membranes with
      chorioamnionitis displayed a 8-fold decrease in hyaluronan concentration as well
      as a pronounced (88%) degradation of decorin and biglycan (p < 0.05). The amnion
      from preterm elective caesarean sections had higher decorin (3.2 vs. 1.7 MUg/mg,
      p < 0.05) and lower biglycan (0.4 vs. 1.0 MUg/mg, p < 0.05) concentrations as
      compared to similar term amnion (p < 0.05), whereas the hyaluronan concentrations
      were not associated with gestational age. Also the chorio-decidua from preterm
      caesarean sections had higher decorin concentrations (1.8 vs. 1.0 MUg/mg, p <
      0.05) whereas the biglycan concentration was unchanged. Labour (term as well as
      preterm) was characterized by increased hyaluronan and biglycan concentrations in
      the amnion (not statistically significant). CONCLUSION: The biglycan/decorin
      balance increases during third trimester of pregnancy and during active labour.
      This relation might contribute to mechanical weakening of the membranes.
      Chorioamnionitis induces dramatic degradation of both proteoglycans and
      hyaluronan, which can explain the decreased biomechanical strength.

PMID- 24920508
TI  - Solitary cystic cerebellar metastasis in a patient with invasive transitional
      cell carcinoma of the bladder.
AB  - Transitional cell carcinoma of the bladder (TCC) represents nearly 90% of
      genitourinary malignancies and typically presents with locally invasive symptoms.
      Metastasis to the central nervous system (CNS) is uncommon occurring in <5% of
      patients. When present, metastatic lesions are typically solid, isolated and
      located in the cerebrum. We report a case of a patient with a history of TCC who
      presented with lethargy and ataxia and was found to have a solitary cystic
      cerebellar lesion consistent with metastatic disease. Unfortunately, the
      prognosis for patients with TCC and CNS metastases is poor. Treatment options
      include debulking surgery, whole brain radiation, stereotactic radiosurgery and
      chemotherapy. Unfortunately, treatment may not appreciably extend survival and
      care is often supportive in previously reported cases. Though uncommon, TCC can
      metastasise to the CNS and should be considered in the differential diagnosis of
      patients, particularly those who were treated with aggressive surgery or
      combination chemotherapy previously. 

PMID- 24920509
TI  - Exceptional localisation of an ectopic parathyroid adenoma at the level of the
      hyoid bone.
AB  - Primary hyperparathyroidism is characterised by high parathyroid hormone (PTH)
      levels and concomitant hypercalcaemia. Ninety per cent is caused by solitary
      parathyroid adenomas, 10% by multiple adenomas, hyperplasia and carcinomas. Less
      than 0.1% of the inferior parathyroid glands are ectopically located. This case
      is of a 54-year-old woman with hypercalcaemia 3.05 mmol/L and high PTH 22 pmol/L.
      Scintigraphy and CT scan of the neck in 2009 showed no signs of ectopic tissue.
      After treatment with Aredia (pamidronate disodium) infusion, calcium decreased to
      2.73 mmol/L. In 2010 the serum calcium levels increased again to 3 mmol/L.
      Repeated CT showed no ectopic tissue. However, revision of the CT by the
      multidisciplinary team including an experienced endocrine surgeon revealed an
      ectopic parathyroid gland at the level of the hyoid bone, which was surgically
      removed in 2011. Preoperatively the PTH level was 16.8 mmol/L, postoperatively it
      decreased to 2.9 mmol/L, proving a successful excision. In case of suspicion of a
      parathyroid adenoma a CT of the neck should be thoroughly assessed by a dedicated
      multidisciplinary team, including the head and neck surgeon, as clinical data and
      radiological findings must be combined since ectopic parathyroid adenomas are a
      rare entity. Thereafter the adenoma can be surgically removed and the patient
      cured.

PMID- 24920510
TI  - A rare benign odontogenic neoplasm: peripheral odontogenic fibroma.
AB  - The peripheral odontogenic fibroma is a relatively rare, benign, unencapsulated
      and gingival mass of fibrous connective tissue, considered to be the extraosseous
      counterpart of the central odontogenic fibroma. Peripheral odontogenic fibroma
      was earlier quite commonly confused with peripheral ossifying fibroma, until WHO
      classification (1992), classified it under odontogenic tumours. Peripheral
      odontogenic fibroma is seen so infrequently that little is known about this
      neoplasm; the largest series of cases have been that of Farman who found five
      cases in the literature and added another 10 cases. Through this case report we
      try to clarify the features of this condition and attempt to clear its
      distinction with other commonly occurring conditions. 

PMID- 24920511
TI  - Delayed onset panuveitis following intravitreal aflibercept injection.
AB  - Aflibercept has been listed on the Australian Pharmaceutical Benefit Scheme for
      the past year for neovascular age-related macular degeneration. Since that time
      there have not been any reports of delayed onset panuveitis. We present two cases
      of anterior and posterior uveitis that have occurred 4 weeks or more after first
      intravitreal injection of aflibercept. Both patients had received other vascular
      endothelial growth factor inhibitors prior to aflibercept administration without
      signs of inflammation and both cases had sterile endophthalmitis. On resolution
      of the inflammation the patients were recommenced on ranibizumab without further
      incident.

PMID- 24920512
TI  - Bilateral optic neuropathy associated with cryptococcal meningitis in an
      immunocompetent patient.
AB  - Cryptococcal meningitis is associated with significant morbidity and is rare
      among immunocompetent patients. Clinical presentation as well as the course of
      disease is usually indolent which may delay the diagnosis. We present the case of
      a 52-year-old woman admitted with headaches, vomiting and fatigue for 3 weeks.
      She was diagnosed with cryptococcal meningitis and treated with antifungal
      therapy. She was referred for ophthalmological examination presenting with
      decreased vision in the left eye (OS; count fingers), left relative afferent
      pupillary defect and bilateral sixth nerve palsy. Funduscopy revealed florid
      bilateral papilloedema. Cranial MRI showed indirect signs of intracranial
      hypertension as well as multiple parenchymal lesions and optic nerve sheath
      enhancement after contrast administration. A ventriculoperitoneal shunt was
      placed. In spite of the control of intracranial pressure there was a decrease in
      vision in the right eye (OD) and deterioration of visual fields. Intravenous
      methylprednisolone was used to reverse optic neuropathy and to prevent OD visual
      loss.

PMID- 24920513
TI  - Coronary spasm as the cause of myocardial ischaemia in a patient with anomalous
      origin of the left anterior descending artery from the proximal right coronary
      artery.
AB  - A 49-year-old woman developed angina at rest. A CT of the coronary artery
      revealed that the left anterior descending artery arose from the right coronary
      artery, and traversed between the aorta and pulmonary trunk. An exercise stress
      myocardial scintigraphy did not reproduce myocardial ischaemia or anginal
      symptoms. A coronary angiography did not show any atherosclerotic changes.
      Finally, an ergotamine provocation test for vasospasm revealed diffuse severe
      spasm in the right coronary artery and the left anterior descending artery.
      Surgical correction of the anomaly was deferred and the patient was managed with
      medications to control spasm with good clinical outcome. 

PMID- 24920514
TI  - Metastatic spinal abscesses from diabetic foot osteomyelitis.
AB  - A 66-year-old man with long-standing type 2 diabetes, nephropathy and neuropathy
      was admitted acutely with an infected left big toe neuropathic ulcer, with
      underlying osteomyelitis. His condition rapidly deteriorated with sepsis and
      right lobar pneumonia. Microbiology grew methicillin-sensitive Staphylococcus
      aureus. Shortly into his admission, he developed flaccid paraparesis, and an MRI
      showed multiple epidural abscesses with likely cord infarction, not amenable to
      surgical intervention. His sepsis resolved, but his paraparesis remained severe,
      requiring spinal rehabilitation. 

PMID- 24920515
TI  - Intracerebral bleed, right haemiparesis and seizures: an atypical presentation of
      vivax malaria.
AB  - Falciparum malaria is notoriously known to produce life-threatening
      complications. Despite growing reports of chloroquine resistance and severe
      disease, vivax malaria continues to be viewed as a benign disease. We report a
      rare case of a 47-year-old healthy man from a malaria-endemic region, presenting
      with intracerebral bleed, right haemiparesis, aphasia and seizures following
      vivax malaria. This was successfully managed conservatively, without any
      neurosurgical intervention, with combination therapy of intravenous artesunate,
      oral hydroxychloquine and primaquine. In a country where Plasmodium vivax is
      responsible for majority of cases of malaria, it is high time the national
      malaria control programmes focus on the elimination of P. vivax in addition to
      its more dangerous counterpart, P. falciparum. 

PMID- 24920516
TI  - Oesophageal inflammatory paediatric chylothorax.
AB  - Paediatric chylothoraces are rare, particularly outside the operative setting.
      Cases of spontaneous chylothorax are often demanding diagnostically and
      frequently associated with patient morbidity. We present a challenging case of
      paediatric chylothorax associated with inflammatory oesophageal perforation
      likely related to foreign body ingestion. 

PMID- 24920517
TI  - Peptide nanotubes.
AB  - The self-assembly of different classes of peptide, including cyclic peptides,
      amyloid peptides and surfactant-like peptides into nanotube structures is
      reviewed. The modes of self-assembly are discussed. Additionally, applications in
      bionanotechnology and synthetic materials science are summarized. 

PMID- 24920519
TI  - Alumina-clay nanoscale hybrid filler assembling in cross-linked polyethylene
      based nanocomposites: mechanics and thermal properties.
AB  - Herein, investigation on XLPE-Al2O3-clay ternary hybrid systems of Al2O3 and clay
      in 1 : 1 and 2 : 1 ratios, binary systems of XLPE-clay and XLPE-Al2O3
      nanocomposites, with special reference to the hybrid filler effect and the
      superior microstructural development in ternary systems is conducted. The ternary
      hybrid composite of Al2O3 and clay in a 1 : 1 ratio exhibits the highest tensile
      strength (100% increase) and Young's modulus (208% increase), followed by the
      Al2O3 : clay = 2 : 1 system. The interaction between alumina and clay altered the
      composite morphology, filler dispersion and gave rise to a unique filler
      architecture leading to a substantial boost up in mechanics compared to
      predictions based on the idealized filler morphology. Experimentally observed
      much higher mechanics compared to theoretical predictions confirmed that the
      dramatic improvement in mechanics is the outcome of the positive hybrid effect
      and a second factor of synergism, i.e. filler-filler networks. Morphological
      control of the hybrid filler network is realized by adjusting the ratio between
      different fillers. For the Al2O3 : clay = 2 : 1 system, the microstructural
      limitation of dispersion due to the steric effect of alumina clusters shifts the
      properties to the negative hybrid effect region. 

PMID- 24920518
TI  - Development of a patient decision aid for people with refractory angina: protocol
      for a three-phase pilot study.
AB  - BACKGROUND: Refractory angina is a severe chronic disease, defined as angina
      which cannot be controlled by usual treatments for heart disease. This disease is
      frightening, debilitating, and difficult to manage. Many people suffering
      refractory have inadequate pain relief, continually revisit emergency departments
      for help, undergo repeated cardiac investigations, and struggle with obtaining
      appropriate care. There is no clear framework to help people understand the risks
      and benefits of available treatment options in Canada. Some treatments for
      refractory angina are invasive, while others are not covered by provincial health
      insurance plans. Effective care for refractory angina sufferers in Canada is
      critically underdeveloped; it is important that healthcare professionals and
      refractory angina sufferers alike understand the treatment options and their
      implications. This proposal builds on the recent Canadian practice guidelines for
      the management of refractory angina. We propose to develop a decision support
      tool in order to help people suffering from refractory angina make well-informed
      decisions about their healthcare and reduce their uncertainty about treatment
      options. METHODS: This project will be conducted in three phases: a) development
      of the support tool with input from clinical experts, the Canadian refractory
      angina guidelines, and people living with refractory angina, b) pilot testing of
      the usability of the tool, and c) formal preliminary evaluation of the
      effectiveness of the support tool to help people make informed decisions about
      treatment options. DISCUSSION: A decision support tool for refractory angina is
      needed and the available data suggest that by developing such a tool, we may be
      able to help refractory angina sufferers better understand their condition and
      the effectiveness of available treatment options (in their respective clinical
      settings) as well as their implications (e.g. risks vs. benefits). By virtue of
      this tool, we may also be able to facilitate identification and inclusion of
      patients' values and preferences in the decision making process. This is
      particularly important as refractory angina is an intractable condition,
      necessitating that the selected course of treatment be lifelong. This study will
      yield a much needed patient decision aid for people living with refractory angina
      and pilot data to support a subsequent effectiveness study.

PMID- 24920520
TI  - Sound analysis of a musical performance to evaluate prosthodontic treatment for a
      clarinet player.
AB  - Some dental patients use the orofacial region to play wind instruments; however,
      musical performance has not been objectively evaluated following prosthodontic
      treatment in such patients. The purpose of this report was to describe
      prosthodontic treatment for a clarinet player using sound analysis. The patient
      required a removable partial denture for his maxillary anterior teeth. Sound
      analysis was performed before and after denture adjustment, and the patient
      completed a questionnaire regarding his perceptions while playing his clarinet.
      After adjustment, the denture showed better performance, and patient satisfaction
      increased compared with that before adjustment. 

PMID- 24920521
TI  - An epichlorohydrin-crosslinked semi-interpenetrating GG-PEO network as a xerogel
      matrix for sustained release of sulpiride.
AB  - The current study involved the development of a novel sustained release
      crosslinked semi-IPN xerogel matrix tablet prepared by chemical crosslinking of
      poly(ethylene) oxide (PEO) and gellan gum (GG) employing epichlorohydrin (EPI) as
      crosslinker. A Box-Behnken design was employed for the statistical optimization
      of the matrix system to ascertain the ideal combination of native polymeric and
      crosslinking agents. Characterization studies were performed by employing
      standard polymer characterization techniques such as Fourier transform infrared
      spectrometry, differential scanning calorimetry, and scanning electron
      microscopy. Formulated matrix tablets displayed zero-order release kinetics,
      extending over 24 h. The mechanism of drug release was primarily by swelling and
      surface erosion. Crosslinked semi-IPN xerogel matrix tablets were compared to non
      crosslinked polymer blends; results from the study conducted showed that the
      physiochemical properties of the PEO and GG were sufficiently modified to allow
      for sustained release of sulpiride with a 100% drug release at 24 h in a
      controlled manner as compared to non-crosslinked formulations which displayed
      further release beyond the test period. Crosslinked formulations displayed water
      uptake between 450 and 500% indicating a controlled rate of swelling and erosion
      allowing for sustained release. Surface morphology of the crosslinked system
      depicted a porous structure formed by interpenetrating networks of polymers,
      allowing for a greater degree of controlled penetration into the system affording
      it the ability to sustain drug release. Therefore, conclusively, based on the
      study performed, crosslinked PEO-GG allows for the sustained release of sulpiride
      from a hydrophilic semi-IPN xerogel matrix system. 

PMID- 24920522
TI  - Preclinical formulations: insight, strategies, and practical considerations.
AB  - A lot of resources and efforts have been directed to synthesizing potentially
      useful new chemical entities (NCEs) by pharmaceutical scientists globally.
      Detailed physicochemical characterization of NCEs in an industrial setup begins
      almost simultaneously with preclinical testing. Most NCEs possess poor water
      solubility posing bioavailability issues during initial preclinical screening,
      sometimes resulting in dropping out of an NCE with promising therapeutic
      activity. Selection of right formulation approach for an NCE, based on its
      physicochemical properties, can aid in improving its solubility-related
      absorption and bioavailability issues. The review focuses on preclinical
      formulations stressing upon different preclinical formulation strategies and
      deciphers the understanding of formulation approaches that could be employed. It
      also provides detailed information related to a vast pool of excipients available
      today, which is of immense help in designing preclinical formulations. Few
      examples mentioned, throw light on key aspects of preclinical formulation
      development. The review will serve as an important guide for selecting the right
      strategy to improve bioavailability of NCEs for academic as well as industrial
      formulation scientists. 

PMID- 24920523
TI  - Effect of ascorbic acid on the degradation of cyanocobalamin and hydroxocobalamin
      in aqueous solution: a kinetic study.
AB  - The degradation kinetics of 5 * 10(-5) M cyanocobalamin (B12) and
      hydroxocobalamin (B12b) in the presence of ascorbic acid (AH2) was studied in the
      pH range of 1.0-8.0. B12 is degraded to B12b which undergoes oxidation to corrin
      ring cleavage products. B12b alone is directly oxidized to the ring cleavage
      products. B12 and B12b in degraded solutions were simultaneously assayed by a two
      component spectrometric method at 525 and 550 nm without interference from AH2.
      Both degrade by first-order kinetics and the values of the rate constants at pH
      1.0-8.0 range from 0.08 to 1.05 * 10(-5) s(-1) and 0.22-7.62 * 10(-5) s(-1),
      respectively, in the presence of 0.25 * 10(-3) M AH2. The t 1/2 values of B12 and
      B12b range from 13.7 to 137.5 h and 2.5-87.5 h, respectively. The second-order
      rate constants for the interaction of AH2 with B12 and B12b are 0.05-0.28 * 10(
      2) and 1.10-30.08 * 10(-2) M(-1) s(-1), respectively, indicating a greater effect
      of AH2 on B12b compared to that of B12. The k obs-pH profiles for both B12 and
      B12b show the highest rates of degradation around pH 5. The degradation of B12
      and B12b by AH2 is affected by the catalytic effect of phosphate ions on the
      oxidation of AH2 in the pH range 6.0-8.0. 

PMID- 24920524
TI  - Combined use of crystalline sodium salt and polymeric precipitation inhibitors to
      improve pharmacokinetic profile of ibuprofen through supersaturation.
AB  - To maximize the pharmacological effect of a pain reliever such as ibuprofen,
      early onset of action is critical. Unfortunately, the acidic nature of ibuprofen
      minimizes the amount of drug that can be solubilized under gastric conditions and
      would be available for immediate absorption upon entry into the intestine.
      Although the sodium salt of ibuprofen has higher solubility, rapid conversion
      from the salt to the poorly soluble free acid phase occurs under gastric
      conditions. Therefore, the combination of the highly soluble sodium salt form of
      ibuprofen with polymers was evaluated as an approach to prolong supersaturation
      of ibuprofen during the disproportionation of the salt. Binary combinations of
      ibuprofen sodium with polymers resulted in the identification of several
      formulations that demonstrated high degrees and extended durations of
      supersaturation during in vitro dissolution experiments. These formulations
      included HPMC, polyvinyl pyrrolidone-vinyl acetate copolymer (PVP-VA64),
      methylcellulose (MC), and hydroxypropyl cellulose (HPC). The in vitro
      supersaturation observed with these ibuprofen-polymer formulations translated to
      an increase in Cmax and an earlier Tmax for the PVP-VA64, MC, and HPC
      formulations relative to ibuprofen only controls when administered orally to rats
      under fasted conditions. Based on these observations, combining ibuprofen sodium
      with polymers such as PVP-VA64, MC, or HPC is a viable formulation approach to
      prolong supersaturation in the stomach and enable an optimized pharmacokinetic
      profile in vivo where rapid onset of action is desired. 

PMID- 24920525
TI  - Skin findings in Williams syndrome.
AB  - Previous examination in a small number of individuals with Williams syndrome
      (also referred to as Williams-Beuren syndrome) has shown subtly softer skin and
      reduced deposition of elastin, an elastic matrix protein important in tissue
      recoil. No quantitative information about skin elasticity in individuals with
      Williams syndrome is available; nor has there been a complete report of
      dermatologic findings in this population. To fill this knowledge gap, 94 patients
      with Williams syndrome aged 7-50 years were recruited as part of the skin and
      vascular elasticity (WS-SAVE) study. They underwent either a clinical
      dermatologic assessment by trained dermatologists (2010 WSA family meeting) or
      measurement of biomechanical properties of the skin with the DermaLabTM suction
      cup (2012 WSA family meeting). Clinical assessment confirmed that soft skin is
      common in this population (83%), as is premature graying of the hair (80% of
      those 20 years or older), while wrinkles (92%), and abnormal scarring (33%) were
      detected in larger than expected proportions. Biomechanical studies detected
      statistically significant differences in dP (the pressure required to lift the
      skin), dT (the time required to raise the skin through a prescribed gradient), VE
      (viscoelasticity), and E (Young's modulus) relative to matched controls. The RT
      (retraction time) also trended longer but was not significant. The biomechanical
      differences noted in these patients did not correlate with the presence of
      vascular defects also attributable to elastin insufficiency (vascular stiffness,
      hypertension, and arterial stenosis) suggesting the presence of tissue specific
      modifiers that modulate the impact of elastin insufficiency in each tissue.

PMID- 24920526
TI  - What you know can influence what you are going to know (especially for older
      adults).
AB  - Stimuli related to an individual's knowledge/experience are often more memorable
      than abstract stimuli, particularly for older adults. This has been found when
      material that is congruent with knowledge is contrasted with material that is
      incongruent with knowledge, but there is little research on a possible graded
      effect of congruency. The present study manipulated the degree of congruency of
      study material with participants' knowledge. Young and older participants
      associated two famous names to nonfamous faces, where the similarity between the
      nonfamous faces and the real famous individuals varied. These associations were
      incrementally easier to remember as the name-face combinations became more
      congruent with prior knowledge, demonstrating a graded congruency effect, as
      opposed to an effect based simply on the presence or absence of associations to
      prior knowledge. Older adults tended to show greater susceptibility to the effect
      than young adults, with a significant age difference for extreme stimuli, in line
      with previous literature showing that schematic support in memory tasks
      particularly benefits older adults. 

PMID- 24920527
TI  - Procedures for assessing psychological predictors of injuries in circus artists:
      a pilot prospective study.
AB  - BACKGROUND: Research on psychological risk factors for injury has focused on
      stable traits. Our objective was to test the feasibility of a prospective
      longitudinal study designed to examine labile psychological states as risk
      factors of injury. METHODS: We measured psychological traits at baseline (mood,
      ways of coping and anxiety), and psychological states every day (1-item questions
      on anxiety, sleep, fatigue, soreness, self-confidence) before performances in
      Cirque du Soleil artists of the show "O". Additional questions were added once
      per week to better assess anxiety (20-item) and mood. Questionnaires were
      provided in English, French, Russian and Japanese. Injury and exposure data were
      extracted from electronic records that are kept as part of routine business
      practices. RESULTS: The 43.9% (36/82) recruitment rate was more than expected.
      Most artists completed the baseline questionnaires in 15 min, a weekly
      questionnaire in <2 min and a daily questionnaire in <1 min. We improved the
      formatting of some questions during the study, and adapted the wording of other
      questions to improve clarity. There were no dropouts during the entire study,
      suggesting the questionnaires were appropriate in content and length. Results for
      sample size calculations depend on the number of artists followed and the minimal
      important difference in injury rates, but in general, preclude a purely
      prospective study with daily data collection because of the long follow-up
      required. However, a prospective nested case-crossover design with data
      collection bi-weekly and at the time of injury appears feasible. CONCLUSION: A
      prospective study collecting psychological state data from subjects who train and
      work regularly together is feasible, but sample size calculations suggest that
      the optimal study design would use prospective nested case-crossover methodology.

PMID- 24920528
TI  - Markers for visceral hypersensitivity in patients with irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a heterogenous disorder with
      visceral hypersensitivity as important hallmark. It is not known whether IBS
      patients with visceral hypersensitivity have different epidemiological and
      clinical characteristics compared with IBS patients without visceral
      hypersensitivity. Aim of our study was to compare in detail a large group of
      hyper- vs normosensitive IBS patients with respect to epidemiological and
      clinical characteristics. METHODS: IBS patients (Rome III criteria) have been
      recruited for a large-scale cohort study. All patients from this cohort who
      underwent a rectal barostat procedure were included and allocated based on those
      with and without visceral hypersensitivity. Patient demographics, and symptoms
      were collected using questionnaires (GSRS, HADS, SF-36) and a 14-day symptom
      diary for IBS-related symptoms. A multivariate logistic regression model was used
      to identify risk markers for having visceral hypersensitivity. KEY RESULTS:
      Ninety-five normosensitive and 93 hypersensitive IBS patients participated in
      this study. Hypersensitive patients had significantly higher scores for GSRS
      abdominal pain (p < 0.05), indigestion, reflux and constipation syndrome (all p <
      0.01), and IBS symptom intensity, discomfort (both p < 0.05) and mean symptom
      composite score (p < 0.01). Age, female sex, and the use of SSRI medication were
      significantly different between the normo- and the hypersensitive IBS patients.
      However, after adjustment for other risk markers, only increasing age was found
      to be significantly associated with lower odds for having hypersensitivity (OR
      0.97 [95% CI: 0.94; 0.99]). CONCLUSIONS & INFERENCES: Apart from more severe
      symptomatology, hypersensitive IBS patients are characterized by significantly
      younger age compared with normosensitive IBS patients. The study has been
      registered in the US National Library of Medicine (http://www.clinicaltrials.gov,
      NCT00702026).

PMID- 24920529
TI  - Revealing microbial functional activities in the Red Sea sponge Stylissa carteri
      by metatranscriptomics.
AB  - Sponges are important components of marine benthic environments and are
      associated with microbial symbionts that carry out ecologically relevant
      functions. Stylissa carteri is an abundant, low-microbial abundance species in
      the Red Sea. We aimed to achieve the functional and taxonomic characterization of
      the most actively expressed prokaryotic genes in S. carteri. Prokaryotic mRNA was
      enriched from sponge total RNA, sequenced using Illumina HiSeq technology and
      annotated using the metagenomics Rapid Annotation using Subsystem Technology (MG
      RAST) pipeline. We detected high expression of archaeal ammonia oxidation and
      photosynthetic carbon fixation by members of the genus Synechococcus. Functions
      related to stress response and membrane transporters were among the most highly
      expressed by S. carteri symbionts. Unexpectedly, gene functions related to
      methylotrophy were highly expressed by gammaproteobacterial symbionts. The
      presence of seawater-derived microbes is indicated by the phylogenetic proximity
      of organic carbon transporters to orthologues of members from the SAR11 clade. In
      summary, we revealed the most expressed functions of the S. carteri-associated
      microbial community and linked them to the dominant taxonomic members of the
      microbiome. This work demonstrates the applicability of metatranscriptomics to
      explore poorly characterized symbiotic consortia and expands our knowledge of the
      ecologically relevant functions carried out by coral reef sponge symbionts. 

PMID- 24920530
TI  - Identification of drug-induced myocardial infarction-related protein targets
      through the prediction of drug-target interactions and analysis of biological
      processes.
AB  - Drug-induced myocardial infarction (DIMI) is one of the most serious adverse drug
      effects that often lead to death. Therefore, the identification of DIMI at the
      early stages of drug development is essential. For this purpose, the in vitro
      testing and in silico prediction of interactions between drug-like substances and
      various off-target proteins associated with serious adverse drug reactions are
      performed. However, only a few DIMI-related protein targets are currently known.
      We developed a novel in silico approach for the identification of DIMI-related
      protein targets. This approach is based on the computational prediction of drug
      target interaction profiles based on information from approximately 1738 human
      targets and 828 drugs, including 254 drugs that cause myocardial infarction.
      Through a statistical analysis, we revealed the 155 most significant associations
      between protein targets and DIMI. Because not all of the identified associations
      may lead to DIMI, an analysis of the biological functions of these proteins was
      performed. The Random Walk with Restart algorithm based on a functional linkage
      gene network was used to prioritize the revealed DIMI-related protein targets
      according to the functional similarity between their genes and known genes
      associated with myocardial infarction. The biological processes associated with
      the 155 selected protein targets were determined by gene ontology and pathway
      enrichment analysis. This analysis indicated that most of the processes leading
      to DIMI are associated with atherosclerosis. The revealed proteins were manually
      annotated with biological processes using functional and disease-related data
      extracted from the literature. Finally, the 155 protein targets were classified
      into three categories of confidence: (1) high (the protein targets are known to
      be involved in DIMI via atherosclerotic progression; 50 targets), (2) medium (the
      proteins are known to participate in biological processes related with DIMI; 65
      targets), and (3) low (the proteins are indirectly involved in DIMI pathogenesis;
      40 proteins). 

PMID- 24920531
TI  - Refining the Neuberger model: Uracil processing by activated B cells.
AB  - During the immune response, B cells undergo a programed mutagenic cascade to
      promote increased affinity and expanded antibody function. The two processes,
      somatic hypermutation (SHM) and class switch recombination (CSR), are initiated
      by the protein activation-induced deaminase (AID), which converts cytosine to
      uracil in the immunoglobulin loci. The presence of uracil in DNA promotes DNA
      mutagenesis though a subset of DNA repair proteins. Two distinct mechanisms have
      been proposed to control uracil processing. The first is through base removal by
      uracil DNA glycosylase (UNG), and the second is through detection by the mismatch
      repair (MMR) complex MSH2/6. In a study published in this issue of European
      Journal of Immunology, Dingler et al. [Eur. J. Immunol. 2014. 44: 1925-1935]
      examine uracil processing in B cells in the absence of UNG and SMUG1
      glycosylases. Similar to UNG, SMUG1 is an uracil glycosylase which can remove the
      uracil base. While Smug1(-/-) mice show no clear deficiency in SHM or CSR, Ung(-/
      ) Smug1(-/-) mice display exacerbated phenotypes, suggesting a back-up role for
      SMUG1 in antibody diversity. This new information expands the model of uracil
      processing in B cells and raises several interesting questions about the dynamic
      relationship between base excision repair and MMR. 

PMID- 24920532
TI  - Different imaging modalities in quantification of epicardial adipose tissue
      thickness.

PMID- 24920533
TI  - Genetic dissection of Iddm26 in the spontaneously diabetic BBDP rat.
AB  - The 40 Mb T1D susceptibility locus Iddm26 was mapped to chromosome 2 through
      linkage analysis of a conditioned cross-intercross between the diabetes-prone
      BBDP and the diabetes-resistant ACI.BBDP-Iddm1,Iddm2 (ACI.1u.Lyp). It is flanked
      by Iddm32 and Iddm33, which control the kinetics of disease progression. To fine
      map Iddm26 and characterize immune phenotypes controlled by this locus, several
      congenic sublines were generated carrying smaller, overlapping intervals spanning
      Iddm26 and fragments of Iddm32 and 33. Analysis of disease susceptibility, age of
      disease onset, and immune phenotypes in these sublines identified subloci
      regulating these different parameters. Two ACI.1u.Lyp-derived subloci, Iddm26.1
      and Iddm26.2, imparted significant protection from diabetes, decreasing the
      cumulative incidence by as much as 57% and 28%, respectively. Iddm26.2, which
      overlaps with the human PTPN22 locus, only affected disease susceptibility,
      whereas Iddm26.1 also significantly affected disease kinetics, delaying T1D onset
      by more than 10 days compared with the parental BBDP strain. These Iddm26 subloci
      also regulated various immune phenotypes, including the proportion of splenic
      macrophages by Iddm26.1, and the proportion of activated T-cells in secondary
      lymphoid organs by Iddm26.2. The analysis of Iddm26 congenic animals in two
      different SPF facilities demonstrated that the influence of this locus on T1D is
      environment-dependent.

PMID- 24920535
TI  - Structural and mechanistic insights into an Fe3+-triggered quinazoline based
      molecular rotor.
AB  - Highly fluorescent, multifunctional and thermoreversible conformational switching
      (1) has been designed and developed by embedding two imidazo[1,2-c]quinazoline
      (IQ) units in the pyridyl scaffold. The origin of the conformational and optical
      switching of 1 to 1' has been established by various studies and by developing a
      model compound. 

PMID- 24920534
TI  - Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA
      sequencing.
AB  - Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder of the
      esophagus that is compounded by genetic predisposition and hypersensitivity to
      environmental antigens. Using high-density oligonucleotide expression chips, a
      disease-specific esophageal transcript signature was identified and was shown to
      be largely reversible with therapy. In an effort to expand the molecular
      signature of EoE, we performed RNA sequencing on esophageal biopsies from healthy
      controls and patients with active EoE and identified a total of 1607
      significantly dysregulated transcripts (1096 upregulated, 511 downregulated).
      When clustered by raw expression levels, an abundance of immune cell-specific
      transcripts are highly induced in EoE but expressed at low (or undetectable)
      levels in healthy controls. Moreover, 66% of the gene signature identified by RNA
      sequencing was previously unrecognized in the EoE transcript signature by
      microarray-based expression profiling and included several long non-coding RNAs
      (lncRNA), an emerging class of transcriptional regulators. The lncRNA BRAF
      activated non-protein coding RNA (BANCR) was upregulated in EoE and induced in
      interleukin-13 (IL-13)-treated primary esophageal epithelial cells. Repression of
      BANCR significantly altered the expression of IL-13-induced proinflammatory
      genes. Together, these data comprise new potential biomarkers of EoE and
      demonstrate a novel role for lncRNAs in EoE and IL-13-associated responses. 

PMID- 24920536
TI  - Chromium resistance of dandelion (Taraxacum platypecidum Diels.) and bermudagrass
      (Cynodon dactylon [Linn.] Pers.) is enhanced by arbuscular mycorrhiza in Cr(VI)
      contaminated soils.
AB  - In a greenhouse pot experiment, dandelion (Taraxacum platypecidum Diels.) and
      bermudagrass (Cynodon dactylon[Linn.] Pers.), inoculated with and without
      arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis, were grown in
      chromium (Cr)-amended soils (0 mg/kg, 5 mg/kg, 10 mg/kg, and 20 mg/kg Cr[VI]) to
      test whether arbuscular mycorrhizal (AM) symbiosis can improve Cr tolerance in
      different plant species. The experimental results indicated that the dry weights
      of both plant species were dramatically increased by AM symbiosis. Mycorrhizal
      colonization increased plant P concentrations and decreased Cr concentrations and
      Cr translocation from roots to shoots for dandelion; in contrast, mycorrhizal
      colonization decreased plant Cr concentrations without improvement of P nutrition
      in bermudagrass. Chromium speciation analysis revealed that AM symbiosis
      potentially altered Cr species and bioavailability in the rhizosphere. The study
      confirmed the protective effects of AMF on host plants under Cr contaminations.

PMID- 24920537
TI  - Bay-type H...H "bonding" in cis-2-butene and related species: QTAIM versus NBO
      description.
AB  - We use comparative natural bond orbital (NBO) and quantum theory of atoms in
      molecules (QTAIM) methods to analyze the proximal bay-type H...H interactions in
      cis-2-butene and related species, which lead to controversial interpretation as
      attractive "H?H bonding" in the QTAIM framework. We address the challenging
      questions concerning well established structural, conformational, and vibrational
      properties of such species that appear to be sharply at odds with the QTAIM
      interpretation. In contrast to the purported "H?H bonding" of QTAIM theory, NBO
      based evaluation of steric (donor-donor) and hyperconjugative (donor-acceptor)
      interactions unambiguously portrays such H...H contacts as dominated by steric
      clashes that are only partially softened by weak secondary hyperconjugative
      interactions, contributing negligibly (bHH  < 0.01) to H...H bond order.
      Additional details of NBO-based versus QTAIM-based description are provided by
      natural bond critical point analysis of topological bond critical point
      properties, which further emphasizes the contrast between the problematic bay
      type H...H contacts and remaining noncontroversial (consensus) chemical bonds.
      NBO analysis is thereby shown to be fully consistent with the traditional
      physical organic concept of repulsive bay-type H...H contacts, including the
      corollary array of structural, conformational, and vibrational properties. (c)
      2014 Wiley Periodicals, Inc. 

PMID- 24920538
TI  - Willingness to join community-based health insurance among rural households of
      Debub Bench District, Bench Maji Zone, Southwest Ethiopia.
AB  - BACKGROUND: Even though Ethiopia bears high burden of diseases, utilization of
      modern health care services is limited. One of the reasons for low utilization of
      healthcare services is the user-fee charges. Moving away from out-of-pocket
      charges for healthcare at the time of use is an important step towards averting
      the financial hardship associated with paying for health service. Prepaid plans
      for health are not accustomed in Ethiopia. Therefore, social and community based
      health insurance schemes were introduced since 2010.In this study, willingness of
      rural households in Debub Bench District, to join community based health
      insurance was assessed. METHOD: Cross-sectional community based study was
      conducted in Debub Bench District in March 2013 using a pretested structured
      questionnaire. Two stage sampling technique was used to select 845 households as
      study units which were allocated to the kebeles proportionately. The sampled
      households were selected using simple random sampling technique. Data were
      entered into EPIDATA 3.0 and analyzed with SPSS version 20. RESULT: Among 845
      sampled households, 808 were interviewed (95.6% response rate). About 78% of the
      respondents were willing to join the scheme. Most of demographic, socioeconomic
      variables and social capital were found to be significantly associated with
      willingness to join community based health insurance. CONCLUSION: If the scheme
      is initiated in the district, majority of the households will enroll in the
      community based health insurance. Farmers, the married households, Bench ethnic
      groups and illiterate, the dominant segments of the population, are more likely
      to enroll the schemes. Therefore initiation of the scheme is beneficial in the
      district.

PMID- 24920539
TI  - Our child is not just a gestational age. A first-hand account of what parents
      want and need to know before premature birth.

PMID- 24920540
TI  - Catalytic self-propulsion of supramolecular capsules powered by polyoxometalate
      cargos.
AB  - Multicompartment, spherical microcontainers were engineered through a layer-by
      layer polyelectrolyte deposition around a fluorescent core while integrating a
      ruthenium polyoxometalate (Ru4POM), as molecular motor, vis-a-vis its oxygenic,
      propeller effect, fuelled upon H2O2 decomposition. The resulting chemomechanical
      system, with average speeds of up to 25 MUm s(-1), is amenable for integration
      into a microfluidic set-up for mixing and displacement of liquids, whereby the
      propulsion force and the resulting velocity regime can be modulated upon H2O2
      controlled addition.

PMID- 24920541
TI  - Recent advances in the genetics and management of harlequin ichthyosis.
AB  - Harlequin ichthyosis (HI) is the most severe and devastating form of the
      autosomal recessive congenital ichthyoses (ARCIs). Mutations in the ABCA12 gene
      result in disruption of intercellular lipid deposition in the stratum corneum and
      a major skin barrier defect. Patients present at birth, often premature, with
      cutaneous thick, yellow, hyperkeratotic plates with deep erythematous fissures,
      causing a typical facial appearance. Harlequin ichthyosis has often been
      considered to be fatal, and management tends to be palliative, but follow-up of
      45 affected infants has shown that with good neonatal care and early introduction
      of oral retinoids, survival rates are improving. Because ABCA12 mutations have
      been identified, known carriers are able to undergo preventative preimplantation
      and prenatal genetic testing. Experimental studies have shown recovery of lipid
      secretion in lamellar granules using corrective gene therapy. Further research is
      needed to develop alternative therapies to retinoids in HI. 

PMID- 24920542
TI  - Antibodies against mucin-based glycopeptides affect Trypanosoma cruzi cell
      invasion and tumor cell viability.
AB  - This study describes the synthesis of glycopeptides NHAc[betaGal]-(Thr)2 
      [alphaGalNAc]-(Thr)2 -[alphaGlcNAc]-(Thr)2 Gly-OVA (1-OVA) and NHAc[betaGal
      alphaGalNAc]-(Thr)3 -[alphaLacNAc]-(Thr)3 -Gly-OVA (2-OVA) as mimetics of both T.
      cruzi and tumor mucin glycoproteins. These glycopeptides were obtained by solid
      phase synthesis, which involved the prior preparation of the protected glycosyl
      amino acids alphaGlcNAc-ThrOH (3), alphaGalNAc-ThrOH (4), betaGal-ThrOH (5),
      alphaLacNAc-ThrOH (6), and betaGal-alphaGalNAc-ThrOH (7) through glycosylation
      reactions. Immunizations of mice with glycopeptides 1-OVA and 2-OVA induced high
      antibody titers (1:16 000), as verified by ELISA tests, whereas flow cytometry
      assays showed the capacity of the obtained anti-glycopeptides 1-OVA and 2-OVA
      antibodies to recognize both T. cruzi and MCF-7 tumor cells. In addition,
      antisera induced by glycopeptides 1-OVA and 2-OVA were also able to inhibit T.
      cruzi fibroblast cell invasion (70 %) and to induce antibody-mediated cellular
      cytotoxicity (ADCC) against MCF-7 cells, with 50 % reduction of cell viability. 

PMID- 24920543
TI  - Signals and noise in the octavolateralis systems: what is the impact of human
      activities on fish sensory function?
AB  - The octavolateralis systems of fishes include the vestibular, auditory, lateral
      line and electrosensory systems. They are united by common developmental and
      neuro-computational features, including hair cell sensors and computations based
      on cross-neuron analyses of differential hair cell stimulation patterns. These
      systems also all use both spectral and temporal filters to separate signals from
      each other and from noise, and the distributed senses (lateral line and
      electroreception) add spatial filters as well. Like all sensory systems, these
      sensors must provide the animal with guidance for adaptive behavior within a
      sensory scene composed of multiple stimuli and varying levels of ambient noise,
      including that created by human activities. In the extreme, anthropogenic
      activities impact the octavolateralis systems by destroying or degrading the
      habitats that provide ecological resources and sensory inputs. At slightly lesser
      levels of effect, anthropogenic pollutants can be damaging to fish tissues, with
      sensory organs often the most vulnerable. The exposed sensory cells of the
      lateral line and electrosensory systems are especially sensitive to aquatic
      pollution. At still lesser levels of impact, anthropogenic activities can act as
      both acute and chronic stressors, activating hormonal changes that may affect
      behavioral and sensory function. Finally, human activities are now a nearly
      ubiquitous presence in aquatic habitats, often with no obvious effects on the
      animals exposed to them. Ship noise, indigenous and industrial fishing
      techniques, and all the ancillary noises of human civilization form a major part
      of the soundscape of fishes. How fish use these new sources of information about
      their habitat is a new and burgeoning field of study. 

PMID- 24920545
TI  - Deadly outbreak of iron storage disease (ISD) in Italian birds of the family
      Turdidae.
AB  - A widespread deadly outbreak occurred in captive birds belonging to the family
      Turdidae in Italy. The present study was performed on 46 dead birds coming from 3
      small decoy-bird breeders in central Italy. Only Turdus pilaris, Turdus iliacus,
      Turdus philomelos and Turdus merula were affected. No other species of bird held
      by these breeders died. A change of diet before the hunting season was reported
      from all breeders. Full necropsy of the animals and histological investigations
      of representative tissue samples were performed. Microscopical examination showed
      marked iron deposits in liver samples. Bacteriological investigations and
      molecular analysis to exclude bacterial and viral diseases were carried out.
      Contamination of food pellet samples by mycotoxins and analysis to detect heavy
      metal contaminants in food pellet samples were considered. An interesting result
      was the high iron content found in food pellets. It was higher than that
      considered suitable for birds, especially for species susceptible to development
      iron storage disease (ISD). Taken together, the results suggested an outbreak of
      ISD caused by the high iron content of food given to the birds before the hunting
      season. The high mortality recorded only in species belonging to the family
      Turdidae suggests a genetic predisposition in the affected birds. 

PMID- 24920546
TI  - Full genome sequences of zebra-borne equine herpesvirus type 1 isolated from
      zebra, onager and Thomson's gazelle.
AB  - A strain of equine herpesvirus type 1 (EHV-1) was isolated from zebra. This
      strain, called "zebra-borne EHV-1", was also isolated from an onager and a
      gazelle in zoological gardens in U.S.A. The full genome sequences of the 3
      strains were determined. They shared 99% identities with each other, while they
      shared 98% and 95% identities with the horse derived EHV-1 and equine herpesvirus
      type 9, respectively. Sequence data indicated that the EHV-1 isolated from a
      polar bear in Germany is one of the zebra-borne EHV-1 and not a recombinant
      virus. These results indicated that zebra-borne EHV-1 is a subtype of EHV-1. 

PMID- 24920547
TI  - Molecular survey of Babesia gibsoni using Haemaphysalis longicornis collected
      from dogs and cats in Japan.
AB  - A nationwide survey of Babesia gibsoni using Haemaphysalis longicornis collected
      from dogs and cats in Japan was conducted using molecular methods. A total of
      1,341 H. longicornis, including 305 females, 14 males, 332 nymphs and 690 larvae
      (153 pools) from 44 prefectures, were examined by B. gibsoni-targeted PCR.
      Partial sequence analysis revealed that 12 of 13 positive samples sequenced,
      including samples from Tottori, Hiroshima, Yamaguchi, Tokushima, Ehime and Oita
      prefectures (all in western Japan), were identical to B. gibsoni, and 1 sample
      from Kyoto Prefecture was most closely related to a Babesia species recently
      detected from feral raccoons in Hokkaido. H. longicornis is a candidate for
      transmission vector tick of the new Babesia species. 

PMID- 24920548
TI  - Effects of low-fat high-fibre diet and mitratapide on body weight reduction,
      blood pressure and metabolic parameters in obese dogs.
AB  - The aim of the present study was to compare the impact on blood pressure and
      different metabolic parameters of a weight-loss program on obese dogs fed on a
      low-fat high-fibre diet and treated with and without mitratapide. The study
      sample consisted of 36 obese dogs, randomly assigned to a control group (n=17),
      which were fed on a low-fat high-fibre diet, and an intervention group (n=19),
      fed on the same diet and treated with mitratapide. Variables measured included
      body condition score, body weight, heart rate, systolic and diastolic blood
      pressures; total cholesterol, triglycerides and glucose levels; alanine
      aminotransferase and alkaline phosphatase activity, measured both at baseline
      (day 0) and at the end of the weight loss program (day 85). All the studied
      parameters had decreased in both groups at the end of the study; these being
      diastolic blood pressure, total cholesterol and alanine aminotransferase,
      significantly lower in dogs treated with mitratapide. The use of mitrapide in
      addition to low-fat high-fibre diet does not seem to offer any further useful
      effect in the loss of weight during the treatment of canine obesity. On the other
      hand, mitratapide seems to present certain beneficial effects on pathologies
      associated with obesity, these being mainly related to blood pressure, lipids and
      hepatic parameters. 

PMID- 24920549
TI  - Knockdown of hTERT by siRNA inhibits cervical cancer cell growth in vitro and in
      vivo.
AB  - Human telomerase reverse transcriptase (hTERT) is the catalytic component of
      telomerase that facilitates tumor cell invasion and proliferation. It has been
      reported that telomerase and hTERT are significantly upregulated in majority of
      cancers including cervical cancer, thus, downregulation of hTERT is a promising
      target in malignant tumor treatment. We established a short interfering RNA
      (siRNA) targeting hTERT, and transfected it into HeLa cells (a cervical cancer
      cell line) to investi-gate the effect of cell proliferation, apoptosis, migration
      and invasion in cervical cancer cells. The results showed that siRNA targeting
      hTERT could effectively knock down hTERT expression, remarkably suppress
      telomerase activity, cell proliferation, migration and invasion, and induced cell
      apoptosis of cervical cancers cells in vitro. In addition, we evaluated whether
      siRNA targeting hTERT affects tumor growth in nude mice, and found that it
      dramatically inhibited tumorigenesis and growth of mice injected with siRNA
      targeting hTERT. Furthermore, we also found that knockdown of hTERT was able to
      significantly suppress constitutive phosphorylation of Akt, PI3K, which might
      imply that reduction of hTERT inhibited tumor growth via the PI3K/Akt signaling
      pathway to some extent. These results suggest that the suppression of hTERT
      expression by siRNA inhibits cervical cancer cell growth in vitro and in vivo,
      and may provide a novel target for anticancer gene therapy.

PMID- 24920550
TI  - The separate and combined effects of hypoxia and sustained recumbency/inactivity
      on sleep architecture.
AB  - PURPOSE: The objective was to determine the separate and combined effects of
      hypoxia and inactivity/unloading on sleep architecture during a 10-day period of
      confinement. METHODS: Ten subjects participated in three 10-day trials in random
      order: hypoxic ambulatory (HAMB), hypoxic bedrest (HBR), and normoxic bedrest
      (NBR). During the HAMB and HBR trials, subjects were confined to a hypoxic
      facility. The hypoxia profile was: simulated altitude of 2,990 m on day 1, 3,380
      m on day 2, and 3,881 m on day 3. In the NBR and HBR trials, subjects maintained
      a horizontal position throughout the confinement period. During each trial, sleep
      polysomnography was conducted one night prior to (baseline; altitude of facility
      is 940 m) and on the first (NT1, altitude 2,990 m) and tenth (NT10, altitude
      3,881 m) night of the 10-day intervention. RESULTS: Average time in sleep stage 1
      decreased from NT1 to NT10 irrespective of trial. Overall incidence and time
      spent in periodic breathing increased from NT1 to NT10 in both HAMB and HBR.
      During NT1, both HAMB and HBR reduced slow-wave sleep and increased light sleep,
      whereas NBR and HBR increased the number of awakenings/night. There were fewer
      awakenings during HAMB than NBR. CONCLUSIONS: Acute exposure to both hypoxia and
      bedrest (HBR) results in greater sleep fragmentation due to more awakenings
      attributed to bedrest, and lighter sleep as a result of reduced slow wave sleep
      caused by the hypoxic environment.

PMID- 24920551
TI  - A new interpolation-free procedure for breath-by-breath analysis of oxygen uptake
      in exercise transients.
AB  - INTRODUCTION: Interpolation methods circumvent poor time resolution of breath-by
      breath oxygen uptake (VO2) kinetics at exercise onset. We report an interpolation
      free approach to the improvement of poor time resolution in the analysis of VO2
      kinetics. METHODS: Noiseless and noisy (10% Gaussian noise) synthetic data were
      generated by Monte Carlo method from pre-selected parameters (Exact Parameters).
      Each data set comprised 10 (VO2)-on transitions with noisy breath distribution
      within a physiological range. Transitions were superposed (no interpolation,
      None), then analysed by bi-exponential model. Fitted model parameters were
      compared with those from interpolation methods (average transition after Linear
      or Step 1-s interpolations), applied on the same data. Experimental data during
      cycling were also analysed. The 95% confidence interval around a line of
      parameters' equality was computed to analyse agreement between exact parameters
      and corresponding parameters of fitted functions. RESULTS: The line of
      parameters' equality stayed within confidence intervals for noiseless synthetic
      parameters with None, unlike Step and Linear, indicating that None reproduced
      Exact Parameters. Noise addition reduced differences among pre-treatment
      procedures. Experimental data provided lower phase I time constants with None
      than with Step. CONCLUSION: In conclusion, None revealed better precision and
      accuracy than Step and Linear, especially when phenomena characterized by time
      constants of <30 s are to be analysed. Therefore, we endorse the utilization of
      None to improve the quality of breath-by-breath [Formula: see text] data during
      exercise transients, especially when a double exponential model is applied and
      phase I is accounted for.

PMID- 24920552
TI  - Bayesian Inference for Reliability of Systems and Networks Using the Survival
      Signature.
AB  - The concept of survival signature has recently been introduced as an alternative
      to the signature for reliability quantification of systems. While these two
      concepts are closely related for systems consisting of a single type of
      component, the survival signature is also suitable for systems with multiple
      types of component, which is not the case for the signature. This also enables
      the use of the survival signature for reliability of networks. In this article,
      we present the use of the survival signature for reliability quantification of
      systems and networks from a Bayesian perspective. We assume that data are
      available on tested components that are exchangeable with those in the actual
      system or network of interest. These data consist of failure times and possibly
      right-censoring times. We present both a nonparametric and parametric approach. 

PMID- 24920553
TI  - Simultaneous determination of linarin, naringenin and formononetin in rat plasma
      by LC-MS/MS and its application to a pharmacokinetic study after oral
      administration of Bushen Guchi Pill.
AB  - A sensitive and reproducible liquid chromatography tandem mass spectrometry (LC
      MS/MS) method was developed and validated for the simultaneous determination of
      linarin, naringenin and formononetin in rat plasma after addition of
      sulfamethoxazole as the internal standard (IS). Separation was carried out on a
      Diamonsil C18 column (150 * 4.6 mm, 5 um) with liner gradient elution using
      methanol (A) and 0.50/00 formic acid aqueous solution (B). Detection was
      performed on a triple-quadrupole linear ion trap mass spectrometer with the
      negative ion electrospray ionization in multiple-reaction monitoring (MRM) mode.
      The MRM transitions were m/z 591.2 -> 283.2, 271.0 -> 150.9, 266.9 -> 252.0 and
      252.0 -> 155.9 for linarin, naringenin, formononetin and IS, respectively. All
      analytes showed good linearity within the concentration range (r > 0.9973). The
      lower limits of quantitation of linarin, naringenin and formononetin were 0.64,
      1.07 and 1.04 ng/mL, respectively. Intra-day and inter-day precisions of the
      investigated components exhibited an RSD within 9.96%, and the accuracy (relative
      error) ranged from -11.25 to 9.38% at all quality control levels. The developed
      method was successfully applied to a pharmacokinetic study of linarin, naringenin
      and formononetin in rats after oral administration of Bushen Guchi Pill.

PMID- 24920554
TI  - Co-expression of CD133, CD44v6 and human tissue factor is associated with
      metastasis and poor prognosis in pancreatic carcinoma.
AB  - The metastasis-related molecules CD133, CD44v6 and human tissue factor (TF) have
      been shown to be associated with tumor invasion and metastasis. This study aimed
      to determine whether co-expression of these three molecules was associated with
      metastasis and overall prognosis in pancreatic carcinoma. We analyzed the
      expression profiles of these three molecules by immunohistochemistry and
      evaluated the relationship of their expression profiles with metastasis and
      prognosis in 109 pancreatic carcinomas. The results showed that the expression
      levels of CD133, CD44v6 and TF were increased in pancreatic carcinoma. Co
      expression of CD133, CD44v6 and TF (tri-expression) was also detected in
      pancreatic carcinoma. Clinical analysis showed that individual expression of
      CD133, CD44v6 or TF was associated with vessel invasion, lymph node metastasis
      and liver metastasis, while tri-expression was associated with lymph node
      metastasis. Survival analysis showed that patients with co-expression of CD133
      and TF or tri-expression had lower and the lowest overall survival rates,
      respectively. Univariate analysis showed that T-factor, lymph node metastasis,
      TNM stage, and individual levels or tri-expression of CD133, CD44v6 and TF were
      survival risk factors. Multivariate analysis showed that tri-expression of CD133,
      CD44v6 and TF was an independent predictor of survival. These results suggest
      that overexpression of CD133, CD44v6 and TF is associated with pancreatic
      carcinoma metastasis. Tri-expression of these three molecules may be a useful
      predictor for pancreatic carcinoma prognosis.

PMID- 24920556
TI  - Atypical case of prenatal cystic epignathus teratoma.

PMID- 24920555
TI  - Cardiac extracellular proteome profiling and membrane topology analysis using
      glycoproteomics.
AB  - PURPOSE: Extracellular proteins are easily accessible, which presents a
      subproteome of molecular targets that have high diagnostic and therapeutic
      potential. Efforts have been made to catalog the cardiac extracellular matridome
      and analyze the topology of identified proteins for the design of therapeutic
      targets. Although many bioinformatics tools have been developed to predict
      protein topology, topology has been experimentally validated for only a very
      small portion of membrane proteins. The aim of this study was to use a
      glycoproteomics and MS approach to identify glycoproteins in the extracellular
      matridome of the infarcted left ventricle (LV) and provide experimental evidence
      for topological determination. EXPERIMENTAL DESIGN: Glycoproteomics analysis was
      performed on eight biological replicates of LV samples from wild-type mice at 7
      days following myocardial infarction using SPE of glycopeptides, followed by mass
      spectrometric identification of N-linked glycosylation sites for topology
      assessment. RESULTS: We identified hundreds of glycoproteins, and the identified
      N-glycosylation sites provide novel information on the correct topology for
      membrane proteins present in the infarct setting. CONCLUSIONS AND CLINICAL
      RELEVANCE: Our data provide the foundation for future studies of the LV infarct
      extracellular matridome, which may facilitate the discovery of drug targets and
      biomarkers.

PMID- 24920557
TI  - Algebraic moment closure for population dynamics on discrete structures.
AB  - Moment closure on general discrete structures often requires one of the
      following: (i) an absence of short-closed loops (zero clustering); (ii) existence
      of a spatial scale; (iii) ad hoc assumptions. Algebraic methods are presented to
      avoid the use of such assumptions for populations based on clumps and are applied
      to both SIR and macroparasite disease dynamics. One approach involves a series of
      approximations that can be derived systematically, and another is exact and based
      on Lie algebraic methods. 

PMID- 24920558
TI  - A single exposure to a sublethal pediocin concentration initiates a resistance
      associated temporal cell envelope and general stress response in Listeria
      monocytogenes.
AB  - Listeria monocytogenes can cause the potentially fatal food-borne disease
      listeriosis, and the use of bacteriocin-producing lactic acid bacteria to control
      L. monocytogenes holds great promise. However, the development of bacteriocin
      resistance is a potential challenge, and the purpose of this study was to
      determine if exposure to sublethal concentrations of pediocin-containing
      Lactobacillus plantarum WHE 92 supernatant could prime L. monocytogenes for
      resistance. By transcriptomic analysis, we found two, 55 and 539 genes
      differentially expressed after 10, 60 and 180 min of exposure to L. plantarum WHE
      92 supernatant as compared with control exposures. We observed temporal
      expression changes in genes regulated by the two component system LisRK and the
      alternative sigma factors SigB and SigL. Additionally, several genes involved in
      bacteriocin resistance were induced. DeltalisR, DeltasigB and DeltasigL mutants
      were all more resistant than wild types to L. plantarum WHE 92 supernatant.
      Conclusively, LisRK, SigB and SigL regulation and genes associated with
      resistance are involved in the temporal adaptive response to pediocin, and all
      three regulatory systems affect pediocin resistance. Thus, a single exposure to a
      sublethal pediocin concentration initiates a response pointing to resistance, and
      indicates that further research exploring the link between adaptive responses and
      resistance is needed. 

PMID- 24920559
TI  - Cardiac autonomic responses at onset of exercise: effects of aerobic fitness.
AB  - Analyzes of cardiac autonomic responses at the initial transient of exercise have
      been used for the investigation of the cardiovascular health. We evaluated the
      influence of aerobic fitness on HR and HRV responses at the onset of exercise. 25
      male subjects (22.3+/-2.4 years) were divided into 2 groups: 'low aerobic
      fitness' (36.2+/-2.6ml.kg(-1).min(-1); n=10) and 'high aerobic fitness' (46.4+/
      5.0ml.kg(-1).min(-1); n=15). The experimental session consisted of assessing the
      beat-to-beat HR at rest and during submaximal exercise. The autonomic responses
      at the onset of exercise were calculated by fitting the HR and HRV (rMSSD-index)
      curves during the initial 300s of exercise into a first-order exponential
      equation. The time constant of HR and of the rMSSD index (tauonHR and tauonrMSSD)
      were calculated for analysis. We observed lower values of tauonrMSSD in the high
      aerobic fitness group compared to the low aerobic fitness group (26.8+/-5s vs.
      38.0+/-18s, respectively; p=0.02). The tauonHR (42.0+/-15 vs. 49.3+/-26s, p=0.38)
      for the groups showed no difference. Aerobic fitness partially influenced the
      autonomic responses during exercise, since individuals with higher fitness showed
      faster decreases in beat-to-beat HRV at the onset of exercise. 

PMID- 24920560
TI  - Effects of local vibration on bone loss in -tail-suspended rats.
AB  - We investigated the effects of vibration (35 Hz, 45 Hz and 55 Hz) as
      countermeasure locally applied to unloading hind limbs on bone, muscle and
      Achilles tendon. 40 female Sprague Dawley rats were divided into 5 groups (n=8,
      each): tail-suspension (TS), TS plus 35 Hz/0.3 g vibration (TSV35), TS plus 45
      Hz/0.3 g vibration (TSV45), TS plus 55 Hz/0.3 g vibration (TSV55) and control
      (CON). After 21 days, bone mineral density (BMD) and the microstructure of the
      femur and tibia were evaluated by MUCT in vivo. The biomechanical properties of
      the femur and Achilles tendon were determined by a materials testing system. Ash
      weight of bone, isotonic contraction and wet weight of soleus were also
      investigated. 35 Hz and 45 Hz localized vibration were able to significantly
      ameliorate the decrease in trabecular BMD (expressed as the percentage change
      from TS, TSV35: 48.11%, TSV45: 31.09%), microstructure and ash weight of the
      femur and tibia induced by TS. Meanwhile, 35 Hz vibration significantly improved
      the biomechanical properties of the femur (57.24% bending rigidity and 41.66%
      Young's modulus vs. TS) and Achilles tendon (45.46% maximum load and 66.67%
      Young's modulus vs. TS). Additionally, Young's modulus of the femur was highly
      correlated with microstructural parameters. Localized vibration was useful for
      counteracting microgravity-induced musculoskeletal loss. In general, the efficacy
      of 35 Hz was better than 45 Hz or 55 Hz in tail-suspended rats. 

PMID- 24920561
TI  - Oxidative stress and inflammation response following aerobic exercise: role of
      ethnicity.
AB  - African-Americans are at a significantly greater risk for developing several
      diseases and conditions. These conditions often have underlying oxidative stress
      mechanisms. Therefore the purpose of this investigation was to ascertain the post
      exercise oxidative response to a single bout of aerobic exercise in African
      American and Caucasian college-age females. A total of 10 African-American and 10
      Caucasian females completed the study. Each subject had her VO2 max measured
      while exercising on a treadmill. A week later, each subject returned to the
      laboratory and performed a 30-min run at 70% of her VO2max. Blood samples were
      taken immediately prior to and following exercise for analysis. Lipid
      hydroperoxides, protein carbonyls, malondialdehyde, xanthine oxidase, glutathione
      in the reduced (GSH) and oxidized (GSSG) forms, TNFalpha and interleukin 6 were
      measured from blood taken before and after exercise. Significance was set at
      p<=0.05 a priori. Xanthine oxidase was the only measure that did not
      significantly increase following exercise. All other markers showed a significant
      elevation in response to the exercise bout with no difference between groups
      except that the Caucasian group had significantly higher malondialdehyde post
      exercise compared to the African-American group. This cohort of college-age
      African-American and Caucasian females showed little difference in their response
      to a single 30-min run at 70% of their max in the markers of oxidative stress
      within the blood. 

PMID- 24920562
TI  - Implantable cardioverter defibrillator in sport participation.
AB  - Although athletic participation lowers cardiovascular risk and improves quality
      of life, it may represent a hazard in high-risk group athletes such as those with
      cardiac abnormalities receiving an implantable cardioverter defibrillator (ICD).
      ICD sports participants are exposed to the potential risk of inappropriate shocks
      due to sinus tachycardia and other supraventricular arrhythmias during exertion
      as well as device injury. The safety of athletic participation of ICD-patients is
      not completely defined and ICD efficacy in interrupting malignant arrhythmias
      during intense exercise is partly unknown. This explains difficulties in current
      recommendations made by physicians, given the associated potentially ischemic,
      autonomic and metabolic conditions. The scope of this review is to underline
      specific considerations including potential risks and recommendations for
      athletic participation in this patient-group. 

PMID- 24920563
TI  - Determination of the optimal load setting for arm crank anaerobic testing in men
      and women.
AB  - This study compared different relative load factors for eliciting the highest
      peak 5 s and mean 30 s absolute power output (watts) during an arm crank 30 s
      Wingate anaerobic power test in 40 upper body trained and recreationally active
      men and women. The relative load factor of 0.075 kg . kg(- 1) BM elicited a
      higher peak 5 s power output than 0.070 and 0.080 kg . kg(- 1) for trained males,
      and 0.070 was higher than 0.055 and 0.080 kg . kg(- 1) for active males (P<0.05).
      In trained women, the peak 5 s power output was greatest at 0.065 kg . kg(- 1)
      and 0.060 kg . kg(- 1) for active women. Mean 30 s power output at a relative
      load factor of 0.060, 0.065 and 0.070 kg . kg(- 1) was higher than 0.080, 0.085
      and 0.090 kg . kg(- 1) in trained men, and mean power output at 0.080 kg . kg(-
      1) was lower than all other relative load factors in active men (P<0.05). Mean 30
      s power was greatest at 0.050 kg . kg(- 1) for trained and active women. In
      conclusion, the optimal relative load factor was different for eliciting peak 5 s
      and mean 30 s power outputs during an arm crank Wingate anaerobic test and
      depends on training status and gender. 

PMID- 24920565
TI  - Advances in the science of objective physical activity monitoring: 3rd
      International Conference on Ambulatory Monitoring of Physical Activity and
      Movement.

PMID- 24920564
TI  - Allometric multilevel modelling of agility and dribbling speed by skeletal age
      and playing position in youth soccer players.
AB  - This study evaluates the contributions of age, skeletal maturation, body size and
      composition, training and playing position to the development of agility and
      dribbling speed in young male soccer players (10-18 years) followed
      longitudinally. 83 players [defenders (n=35), midfielders (n=27), forwards
      (n=21)] were followed annually over 5 years (average: 4.4 observations per
      player). Skeletal age (SA), stature, body mass, triceps and subscapular
      skinfolds, agility and dribbling speed were measured annually. Body composition
      was estimated from the 2 skinfolds. Annual training volume was estimated from
      weekly participation forms completed by coaches. The multiplicative allometric
      models with the best statistical fit showed that statural growth of 1 cm predicts
      1.334 s and 1.927 s of improvement in agility and dribbling speed, respectively.
      Significant independent effects of fat-free mass and annual volume training were
      found for agility and dribbling speed, respectively (P<0.05). Predicted agility
      (from 12 to 18 years of SA) and dribbling speed (from 13 to 18 years of SA)
      differed significantly among players by playing positions
      (midfielders>forwards>defenders). The present results provide developmental
      models for the interpretation of intra- and inter-individual variability in
      agility and dribbling speed among youth soccer players across adolescence, and
      may provide a framework for trainers and coaches to develop and evaluate
      individualized training protocols.

PMID- 24920570
TI  - Methods of dark signal determination for CCD array spectroradiometers used in
      solar UVR measurements.
AB  - The methods of the dark signal determination by direct contemporaneous
      measurements using a light spectrum and modelling of the dark signal based on the
      dark signal characterisation data were discussed. These techniques were tested
      with two charge-couple detectors (CCD) array spectroradiometers used in solar UVR
      measurements. The sensitivity of both instruments was significantly reduced when
      shutters were used; the measured signal varied by up to 12% depending on the
      orientation of the shutter. The shutters should be permanently attached to the
      SSR, so that the orientation cannot be changed to prevent an increase in
      uncertainty. The method of using blind pixels from the optically inactive part of
      the CCD array in a light spectrum could be used to derive the dark signal with
      some limitations for integration times <10 s for the QE65000. An alternative
      method of deriving the dark signal from light measurements using out-of-range
      pixels has been proved impossible due to out-of-range stray light in both
      instruments. The dark signal was characterised for the range of integration times
      and ambient temperatures of 15-35 degrees C. Based on these data, the model of
      the dark signal was developed so that a single value of the dark signal can be
      subtracted over the whole spectral range if the instrument temperature is known. 

PMID- 24920569
TI  - The alteration of the C-terminal region of human frataxin distorts its structural
      dynamics and function.
AB  - Friedreich's ataxia (FRDA) is linked to a deficiency of frataxin (FXN), a
      mitochondrial protein involved in iron-sulfur cluster synthesis. FXN is a small
      protein with an alpha/beta fold followed by the C-terminal region (CTR) with a
      nonperiodic structure that packs against the protein core. In the present study,
      we explored the impact of the alteration of the CTR on the stability and dynamics
      of FXN. We analyzed several pathological and rationally designed CTR mutants
      using complementary spectroscopic and biophysical approaches. The pathological
      mutation L198R yields a global destabilization of the structure correlating with
      a significant and highly localized alteration of dynamics, mainly involving
      residues that are in contact with L198 in wild-type FXN. Variant FXN 90-195,
      which is closely related to the FRDA-associated mutant FXN 81-193, conserves a
      globular shape with a native-like structure. However, the truncation of the CTR
      results in an extreme alteration of global stability and protein dynamics over a
      vast range of timescales and encompassing regions far from the CTR, as shown by
      proton-water exchange rates and (15) N-relaxation measurements. Increased
      sensitivity to proteolysis, observed in vitro for both mutants, suggests a faster
      degradation rate in vivo, whereas the enhanced tendency to aggregate exhibited by
      the truncated variant may account for the loss of functional FXN, with both
      phenomena providing an explanation as to why the alteration of the CTR causes
      FRDA. These results contribute to understanding how stability and activity are
      linked to protein motions and they might be useful for the design of target
      specific ligands to control local protein motions for stability enhancement.

PMID- 24920571
TI  - Skull counting in late stages after internal contamination by actinides.
AB  - Monitoring preparation for internal contamination with actinides (e.g. Pu and Am)
      is required to assess internal doses at nuclear fuel cycle-related facilities. In
      this paper, the authors focus on skull counting in case of single-incident
      inhalation of (241)Am and propose an effective procedure for skull counting with
      an existing system, taking into account the biokinetic behaviour of (241)Am in
      the human body. The predicted response of the system to skull counting under a
      certain counting geometry was found to be only ~1.0 * 10(-5) cps Bq(-1) 1y after
      intake. However, this disadvantage could be remedied by repeated measurements of
      the skull during the late stage of the intake due to the predicted response
      reaching a plateau at about the 1000th day after exposure and exceeding that in
      the lung counting. Further studies are needed for the development of a new
      detection system with higher sensitivity to perform reliable internal dose
      estimations based on direct measurements. 

PMID- 24920572
TI  - Analysis of radon and thoron progeny measurements based on air filtration.
AB  - Measuring of radon and thoron progeny concentrations in air, based on air
      filtration, was analysed in order to assess the reliability of the method.
      Changes of radon and thoron progeny activities on the filter during and after air
      sampling were investigated. Simulation experiments were performed involving
      realistic measuring parameters. The sensitivity of results (radon and thoron
      concentrations in air) to the variations of alpha counting in three and five
      intervals was studied. The concentration of (218)Po showed up to be the most
      sensitive to these changes, as was expected because of its short half-life. The
      well-known method for measuring of progeny concentrations based on air filtration
      is rather unreliable and obtaining unrealistic or incorrect results appears to be
      quite possible. A simple method for quick estimation of radon potential alpha
      energy concentration (PAEC), based on measurements of alpha activity in a
      saturation regime, was proposed. Thoron PAEC can be determined from the
      saturation activity on the filter, through beta or alpha measurements. 

PMID- 24920573
TI  - Perceptions of plain packaging among young adult roll-your-own smokers in France:
      a naturalistic approach.
AB  - BACKGROUND: We explored, for the first time, young adult roll-your-own smokers'
      response to using plain packaging in real-world settings. METHODS: Naturalistic
      research was employed, where 133 French young adult smokers (18-25 years of age)
      used plain roll-your-own packs for 10 days; the plain packs they were provided
      with contained their usual brand of rolling tobacco and displayed the name of
      their usual brand. Participants were recruited in five cities in France (Paris,
      Marseille, Metz, Nantes, Toulouse) and completed two questionnaires to measure
      their response to their own branded packs and the plain packs. Both
      questionnaires assessed pack perceptions, brand attachment, product perceptions
      (eg, taste, quality, natural), feelings about smoking (satisfying, pleasurable),
      feelings when using the pack in front of others (embarrassment, image), warning
      response (credibility, awareness of risks) and smoking-related behaviour (eg,
      consumption, quitting). RESULTS: Compared to their own fully branded packs, plain
      packs were associated with less positive pack and product perceptions, lower
      brand attachment and less positive feelings about smoking and feelings when using
      the pack in front of others. Participants were also more likely to report feeling
      like reducing consumption and quitting when using the plain packs, and more
      likely to feel like missing out on rolling a cigarette. No significant
      differences between the two pack types (plain and branded) were found in terms of
      credibility of warnings and perceptions of level of tar. CONCLUSIONS: The study
      suggests that the impacts of plain packaging for roll-your-own cigarette smokers
      are the same as for smokers of factory-made cigarettes.

PMID- 24920574
TI  - The immediate and long-term changes in support of tobacco display ban after its
      implementation in New Zealand.

PMID- 24920575
TI  - An evaluation of usage patterns, effectiveness and cost of the national smoking
      cessation quitline in Thailand.
AB  - BACKGROUND: Telephone-based smoking cessation services (quitlines) offering
      counselling for smoking cessation without nicotine replacement therapy may be
      important components of tobacco control efforts in low and middle income
      countries, but evaluations in such resource-limited settings are lacking. We
      aimed to evaluate the usage, effectiveness and cost of the Thailand National
      Quitline (TNQ). METHODS: Analysis of retrospective data for callers to the TNQ
      between 2009 and 2012 and a follow-up survey in 1161 randomly selected callers.
      RESULTS: Between 2009 and 2012 there were 116 862 callers to the TNQ; 36 927
      received counselling and at least one follow-up call. Compared with smokers in
      the general population, callers were younger, more highly educated, more likely
      to be students, and more likely to smoke cigarettes rather than roll-your-own
      tobacco. Continuous abstinence rates at 1, 3 and 6 months after calling were
      49.9%, 38.0% and 33.1%. The predicted rate at 12 months was 19.54% (95% CI 14.55
      to 26.24). Average cost per completed counselling was $31 and the average cost
      per quitter was $253. Assuming all (and two-thirds) TNQ callers who succeed in
      quitting would have failed to quit without the assistance of the TNQ, cumulative
      life years saved (LYS) for the 4-year period were 57 238 (36 733) giving a cost
      per LYS of $32 (50) (about 7.93 LYS per quitter) and an estimated return on
      investment over 4 years of 9.01 (5.78). CONCLUSIONS: A low-cost quitline without
      nicotine replacement therapy is a promising model for smoking cessation services
      and likely to offer good value for money in Thailand.

PMID- 24920576
TI  - Are the tobacco industry's claims about the size of the illicit cigarette market
      credible? The case of South Africa.
AB  - BACKGROUND: The tobacco industry claims that illicit cigarette trade in South
      Africa is high and rising. This is often used as an argument not to increase the
      tobacco excise tax or to regulate tobacco products. OBJECTIVES: To determine how
      the tobacco industry's estimates of the size of the illicit cigarette market have
      changed over time. METHODS: Published media articles were obtained from South
      African Press Cuttings; published articles and press releases were sourced from
      the internet. The period of interest is 1990-2012. RESULTS: Between 1990 and 2012
      we found 90 newspaper articles and press statements that emphasised the tobacco
      industry's view on illicit trade. Articles that reported on action taken against
      illicit trade were excluded. Between 2006 and early 2011 the Tobacco Institute of
      Southern Africa, a body representing the interests of large cigarette companies,
      reported that South Africa's illicit cigarette market share was 20%. This share
      increased to 25% in late 2011 and 30% in 2012. In a 2012 presentation by Tobacco
      Institute of Southern Africa to National Treasury the illicit market share in
      2008 was indicated as 7.9%, compared with claims in that year that the illicit
      market share was 20%. Industry findings that the illicit market decreased in 2007
      and 2008 were not reported in the press. CONCLUSIONS: The tobacco industry has
      adjusted previous estimates of the illicit trade share downwards to create the
      impression that illicit trade is high and rising. If previous estimates by the
      tobacco industry were incorrect the credibility of current estimates should be
      questioned.

PMID- 24920577
TI  - Cigarette company trade secrets are not secret: an analysis of reverse
      engineering reports in internal tobacco industry documents released as a result
      of litigation.
AB  - OBJECTIVES: Use previously secret tobacco industry documents to assess tobacco
      companies' routine claims of trade secret protection for information on cigarette
      ingredients, additives and construction made to regulatory agencies, as well as
      the companies' refusal to publicly disclose this information. METHODS: We
      analysed previously secret tobacco industry documents available at
      (http://legacy.library.ucsf.edu) to identify 100 examples of seven major tobacco
      companies' reverse engineering of their competitors' brands between 1937 and
      2001. RESULTS: These reverse engineering reports contain detailed data for 142
      different measurements for at least two companies, including physical parameters
      of the cigarettes, tobacco types, humectants, additives, flavourings, and smoke
      constituents of competitors' cigarettes. These 100 documents were distributed to
      564 employees, including top managers in domestic and foreign offices across
      multiple departments, including executive leadership, research and design,
      product development, marketing and legal. These documents reported new
      competitors' products, measured ingredient changes over time, and informed
      companies' decisions regarding ingredients in their own products. CONCLUSIONS:
      Because cigarette companies routinely analyse their competitors' cigarettes in
      great detail, this information is neither secret nor commercially valuable and,
      thus, does not meet the legal definition of a 'trade secret.' This information is
      only being kept 'secret' from the people consuming cigarettes and the scientific
      community. Public agencies should release this detailed information because it
      would provide valuable information about how ingredients affect addictiveness and
      toxicity, and would help the public health community and consumers better
      understand the impact of cigarette design on human health.

PMID- 24920578
TI  - Sirtuin to the rescue: SIRT2 extends life span of BubR1 mice.

PMID- 24920581
TI  - Introductory paragraph - Volume 28, Issue 7.

PMID- 24920579
TI  - Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin
      receptors.
AB  - We have identified a new function for the dynein adaptor Bicaudal D homolog 1
      (BICD1) by screening a siRNA library for genes affecting the dynamics of
      neurotrophin receptor-containing endosomes in motor neurons (MNs). Depleting
      BICD1 increased the intracellular accumulation of brain-derived neurotrophic
      factor (BDNF)-activated TrkB and p75 neurotrophin receptor (p75(NTR)) by
      disrupting the endosomal sorting, reducing lysosomal degradation and increasing
      the co-localisation of these neurotrophin receptors with retromer-associated
      sorting nexin 1. The resulting re-routing of active receptors increased their
      recycling to the plasma membrane and altered the repertoire of signalling
      competent TrkB isoforms and p75(NTR) available for ligand binding on the neuronal
      surface. This resulted in attenuated, but more sustained, AKT activation in
      response to BDNF stimulation. These data, together with our observation that
      Bicd1 expression is restricted to the developing nervous system when neurotrophin
      receptor expression peaks, indicate that BICD1 regulates neurotrophin signalling
      by modulating the endosomal sorting of internalised ligand-activated receptors. 

PMID- 24920582
TI  - Grief, anger and despair in relatives of severely brain injured patients:
      responding without pathologising.
AB  - The training and expertise of healthcare professionals in diagnosing and treating
      pathology can mean that every situation is treated as an instance of illness or
      abnormality requiring treatment. This medicalised perspective is often evident in
      clinical approaches to family members of people with prolonged disorders of
      consciousness. This editorial was stimulated by reviewing an article (final
      version now published in this issue) concerning the distress of families with
      severely brain injured relatives,(2) and by reading the larger body of literature
      to which that article contributes. It was also prompted by the recent publication
      of national clinical guidelines in the UK about the management of prolonged
      disorders of consciousness. In this editorial we highlight the depth and range of
      emotional reactions commonly experienced by families with a severely brain
      injured relative. We suggest that clinicians should understand such emotions as
      normal responses to a terrible situation, and consider the ways in which clinical
      practice can be adapted to avoid contributing to family trauma. 

PMID- 24920580
TI  - MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing
      fibroblast signatures.
AB  - Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by
      overexpression of cardiac transcription factors or microRNAs. However, induction
      of functional cardiomyocytes is inefficient, and molecular mechanisms of direct
      reprogramming remain undefined. Here, we demonstrate that addition of miR-133a
      (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved
      cardiac reprogramming from mouse or human fibroblasts by directly repressing
      Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133
      overexpression with GMT generated sevenfold more beating iCMs from mouse
      embryonic fibroblasts and shortened the duration to induce beating cells from 30
      to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes,
      upregulated cardiac gene expression, and induced more contracting iCMs with GMT
      transduction, recapitulating the effects of miR-133 overexpression. In contrast,
      overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast
      signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1
      repression was also critical for cardiac reprogramming in adult mouse and human
      cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR
      133/Snai1, is a key molecular roadblock during cardiac reprogramming.

PMID- 24920583
TI  - Is there more to preferences for activity partici-pation among children with
      disabilities?

PMID- 24920584
TI  - Diabetes, obesity, and the Affordable Care Act.

PMID- 24920585
TI  - SGLT inhibition in patients with type 1 diabetes.

PMID- 24920587
TI  - Characterization of plantaris tendon constructs for ankle ligament
      reconstruction.
AB  - BACKGROUND: Many techniques have been described for lateral ligament
      reconstruction. One frequently overlooked autograft option is the plantaris
      tendon, potentially due to the paucity of data on its mechanical characteristics.
      This study examined the structural properties of double and quadruple plantaris
      tendon constructs. METHODS: Plantaris tendons were harvested from 35 fresh-frozen
      human cadaver specimens (mean age, 66 years [range, 43-89 years]; 17 female, 13
      male). The tendon ends were sutured in a running locking technique and then woven
      onto a template board to create double or quadruple graft constructs with a 20-mm
      functional length. If additional tendon length remained, a single 40-mm specimen
      was isolated to provide tissue material properties. Structural properties were
      calculated from the results of cyclic and failure uniaxial tensile tests.
      RESULTS: Quadruple-strand constructs had a tensile strength of 205.8 +/- 68.2 N
      and a stiffness of 133.1 +/- 46.3 N/mm. Single strands had a tensile strength of
      66.9 +/- 26.3 N and a stiffness of 43.8 +/- 14.7 N/mm. Material properties were
      similar to a prior study. CONCLUSIONS: The average maximum tensile strength for
      the quadrupled plantaris grafts exceeded the strength of the intact anterior
      talofibular ligament of 139 to 161 N; therefore, the quadruple plantaris
      construct may be a viable autograft for foot and ankle ligament reconstruction.
      CLINICAL RELEVANCE: The tensile strength of the plantaris tendon is comparable
      to, or stronger than, other grafts already in use and offers a donor site that
      may result in negligible loss of strength.

PMID- 24920586
TI  - Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in
      relapsed/refractory multiple myeloma patients.
AB  - Ixazomib is the first investigational oral proteasome inhibitor to be studied
      clinically. In this phase 1 trial, 60 patients with relapsed/refractory multiple
      myeloma (median of 4 prior lines of therapy; bortezomib, lenalidomide,
      thalidomide, and carfilzomib/marizomib in 88%, 88%, 62%, and 5%, respectively)
      received single-agent ixazomib 0.24 to 2.23 mg/m(2) (days 1, 4, 8, 11; 21-day
      cycles). Two dose-limiting toxicities (grade 3 rash; grade 4 thrombocytopenia)
      occurred at 2.23 mg/m(2). The maximum tolerated dose was 2.0 mg/m(2), which 40
      patients received in 4 expansion cohorts. Patients received a median of 4 cycles
      (range, 1-39); 18% received >=12 cycles. Eighty-eight percent had drug-related
      adverse events, including nausea (42%), thrombocytopenia (42%), fatigue (40%),
      and rash (40%); drug-related grade >=3 events included thrombocytopenia (37%) and
      neutropenia (17%). Grade 1/2 drug-related peripheral neuropathy occurred in 12%
      (no grade >=3). Two patients died on the study (both considered unrelated to
      treatment). The terminal half-life of ixazomib was 3.3 to 7.4 days; plasma
      exposure increased proportionally with dose (0.48-2.23 mg/m(2)). Among 55
      response-evaluable patients, 15% achieved partial response or better (76% stable
      disease or better). These findings have informed the subsequent clinical
      development of ixazomib in multiple myeloma. This trial was registered at
      www.clinicaltrials.gov as #NCT00932698. 

PMID- 24920588
TI  - Number of moles could predict breast cancer risk.

PMID- 24920589
TI  - An unusually powerful mode of low-frequency sound interference due to defective
      hair bundles of the auditory outer hair cells.
AB  - A detrimental perceptive consequence of damaged auditory sensory hair cells
      consists in a pronounced masking effect exerted by low-frequency sounds, thought
      to occur when auditory threshold elevation substantially exceeds 40 dB. Here, we
      identified the submembrane scaffold protein Nherf1 as a hair-bundle component of
      the differentiating outer hair cells (OHCs). Nherf1(-/-) mice displayed OHC hair
      bundle shape anomalies in the mid and basal cochlea, normally tuned to mid- and
      high-frequency tones, and mild (22-35 dB) hearing-threshold elevations restricted
      to midhigh sound frequencies. This mild decrease in hearing sensitivity was,
      however, discordant with almost nonresponding OHCs at the cochlear base as
      assessed by distortion-product otoacoustic emissions and cochlear microphonic
      potentials. Moreover, unlike wild-type mice, responses of Nherf1(-/-) mice to
      high-frequency (20-40 kHz) test tones were not masked by tones of neighboring
      frequencies. Instead, efficient maskers were characterized by their frequencies
      up to two octaves below the probe-tone frequency, unusually low intensities up to
      25 dB below probe-tone level, and growth-of-masker slope (2.2 dB/dB) reflecting
      their compressive amplification. Together, these properties do not fit the
      current acknowledged features of a hypersensitivity of the basal cochlea to lower
      frequencies, but rather suggest a previously unidentified mechanism. Low
      frequency maskers, we propose, may interact within the unaffected cochlear apical
      region with midhigh frequency sounds propagated there via a mode possibly using
      the persistent contact of misshaped OHC hair bundles with the tectorial membrane.
      Our findings thus reveal a source of misleading interpretations of hearing
      thresholds and of hypervulnerability to low-frequency sound interference. 

PMID- 24920590
TI  - DNA looping-dependent autorepression of LEE1 P1 promoters by Ler in
      enteropathogenic Escherichia coli (EPEC).
AB  - Ler, a homolog of H-NS in enteropathogenic Escherichia coli (EPEC), plays a
      critical role in the expression of virulence genes encoded by the pathogenic
      island, locus of enterocyte effacement (LEE). Although Ler acts as an
      antisilencer of multiple LEE operons by alleviating H-NS-mediated silencing, it
      represses its own expression from two LEE1 P1 promoters, P1A and P1B, that are
      separated by 10 bp. Various in vitro biochemical methods were used in this study
      to elucidate the mechanism underlying transcription repression by Ler. Ler acts
      through two AATT motifs, centered at position -111.5 on the coding strand and at
      +65.5 on the noncoding strand, by simultaneously repressing P1A and P1B through
      DNA-looping. DNA-looping was visualized using atomic force microscopy. It is
      intriguing that an antisilencing protein represses transcription, not by steric
      exclusion of RNA polymerase, but by DNA-looping. We propose that the DNA-looping
      prevents further processing of open promoter complex (RPO) at these promoters
      during transcription initiation. 

PMID- 24920591
TI  - In pursuit of an inhibitory drug for the proton channel.

PMID- 24920592
TI  - Predation reduces visual communication distance in an Anolis lizard.

PMID- 24920593
TI  - Redemption of autoreactive B cells.

PMID- 24920595
TI  - Rescuing US biomedical research: some comments on Alberts, Kirschner, Tilghman,
      and Varmus.

PMID- 24920594
TI  - Structure of an antibacterial peptide ATP-binding cassette transporter in a novel
      outward occluded state.
AB  - Enterobacteriaceae produce antimicrobial peptides for survival under nutrient
      starvation. Microcin J25 (MccJ25) is an antimicrobial peptide with a unique lasso
      topology. It is secreted by the ATP-binding cassette (ABC) exporter McjD, which
      ensures self-immunity of the producing strain through efficient export of the
      toxic mature peptide from the cell. Here we have determined the crystal structure
      of McjD from Escherichia coli at 2.7-A resolution, which is to the authors'
      knowledge the first structure of an antibacterial peptide ABC transporter. Our
      functional and biochemical analyses demonstrate McjD-dependent immunity to MccJ25
      through efflux of the peptide. McjD can directly bind MccJ25 and displays a basal
      ATPase activity that is stimulated by MccJ25 in both detergent solution and
      proteoliposomes. McjD adopts a new conformation, termed nucleotide-bound outward
      occluded. The new conformation defines a clear cavity; mutagenesis and ligand
      binding studies of the cavity have identified Phe86, Asn134, and Asn302 as
      important for recognition of MccJ25. Comparisons with the inward-open MsbA and
      outward-open Sav1866 structures show that McjD has structural similarities with
      both states without the intertwining of transmembrane (TM) helices. The occluded
      state is formed by rotation of TMs 1 and 2 toward the equivalent TMs of the
      opposite monomer, unlike Sav1866 where they intertwine with TMs 3-6 of the
      opposite monomer. Cysteine cross-linking studies on the McjD dimer in inside-out
      membrane vesicles of E. coli confirmed the presence of the occluded state. We
      therefore propose that the outward-occluded state represents a transition
      intermediate between the outward-open and inward-open conformation of ABC
      exporters. 

PMID- 24920596
TI  - Systemic addiction to research funding.

PMID- 24920597
TI  - Systemic flaws cannot be fixed with minor tweaks.

PMID- 24920598
TI  - High-power lithium-ion capacitor using LiMnBO3 -nanobead anode and polyaniline
      nanofiber cathode with excellent cycle life.
AB  - LiMnBO3 nanobeads (LMB-NB) with uniform size and distribution were synthesized
      using a urea-assisted microwave/solvothermal method. The potential application of
      LMB-NBs as an anode for a lithium-ion hybrid capacitor (Li-AHC) was tested with a
      polyaniline-nanofiber (PANI-NF) cathode in a nonaqueous LiPF6 (1 M)-ethylene
      carbonate/dimethyl carbonate electrolyte. Cyclic voltammetry (CV) and charge
      discharge (C/DC) studies revealed that the PANI-NF/LMB-NB cell showed an
      exceptional capacitance behavior between 0-3 V along with a prolonged cycle life.
      A discharge capacitance of about 125 F g(-1) , and energy and power densities of
      about 42 Wh kg(-1) and 1500 W kg(-1) , respectively, could be obtained at a
      current density of 1 A g(-1) ; those Li-AHC values are higher relative to cells
      containing various lithium intercalation materials in nonaqueous electrolytes. In
      addition, the PANI-NF/LMB-NB cell also had an outstanding rate performance with a
      capacitance of 54 F g(-1) and a power density of 3250 W kg(-1) at a current
      density of 2.25 A g(-1) and maintained 94% of its initial value after 30000
      cycles. This improved capacitive performance with an excellent electrochemical
      stability could be the result of the morphological features and inherent
      conductive nature of the electroactive species.

PMID- 24920600
TI  - Acute mastoiditis in the pneumococcal conjugate vaccine era.
AB  - Following the introduction of the 7- and 13-valent pneumococcal conjugate
      vaccines, we observed an inverse relationship between the increasing rate of
      immunized children and the proportion of middle ear fluid cultures collected
      during acute mastoiditis episodes that tested positive for Streptococcus
      pneumoniae among a subset of children 0 to 6 years old who had initially
      presented with severe acute otitis media and had bacterial cultures collected
      during tympanocentesis or from spontaneous otorrhea. 

PMID- 24920599
TI  - Nonneutralizing functional antibodies: a new "old" paradigm for HIV vaccines.
AB  - Animal and human data from various viral infections and vaccine studies suggest
      that nonneutralizing antibodies (nNAb) without neutralizing activity in vitro may
      play an important role in protection against viral infection in vivo. This was
      illustrated by the recent human immunodeficiency virus (HIV) RV144 vaccine
      efficacy trial, which demonstrated that HIV-specific IgG-mediated nNAb directed
      against the V2 loop of HIV type 1 envelope (Env) were inversely correlated with
      risk for HIV acquisition, while Env-specific plasma IgA-mediated antibodies were
      directly correlated with risk. However, tier 1 NAb in the subset of responders
      with a low level of plasma Env-specific IgA correlated with decreased risk.
      Nonhuman primate simian immunodeficiency virus (SIV) and simian-human
      immunodeficiency virus (SHIV) challenge studies suggest that Env-mediated
      antibodies are essential and sufficient for protection. A comparison of immune
      responses generated in human efficacy trials reveals subtle differences in the
      fine specificities of the antibody responses, in particular in HIV-specific IgG
      subclasses. The underlying mechanisms that may have contributed to protection
      against HIV acquisition in humans, although not fully understood, are possibly
      mediated by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or other
      nonneutralizing humoral effector functions, such as antibody-mediated
      phagocytosis. The presence of such functional nNAb in mucosal tissues and cervico
      vaginal and rectal secretions challenges the paradigm that NAb are the
      predominant immune response conferring protection, although this does not negate
      the desirability of evoking neutralizing antibodies through vaccination. Instead,
      NAb and nNAb should be looked upon as complementary or synergistic humoral
      effector functions. Several HIV vaccine clinical trials to study these antibody
      responses in various prime-boost modalities in the systemic and mucosal
      compartments are ongoing. The induction of high-frequency HIV-specific functional
      nNAb at high titers may represent an attractive hypothesis-testing strategy in
      future HIV vaccine efficacy trials. 

PMID- 24920601
TI  - Rapeseed oil and ginseng saponins work synergistically to enhance Th1 and Th2
      immune responses induced by the foot-and-mouth disease vaccine.
AB  - Previous investigations demonstrated that saponins isolated from the root of
      Panax ginseng C. A. Meyer (i.e., ginseng root saponin [GS-R]) had adjuvant
      activity. In the present study, the combined effects of rapeseed oil (RO) and GS
      R on the immune responses elicited by foot-and-mouth disease (FMD) vaccine were
      investigated by measuring FMD virus (FMDV)-specific antibody levels, cytokine
      levels, lymphocyte proliferation, and long-lived IgG-secreting plasma cells from
      bone marrow in a mouse model. The results indicated that RO in combination with
      GS-R significantly enhanced serum IgG and isotype concentrations, gamma
      interferon (IFN-gamma) and interleukin 5 (IL-5) levels, splenocyte proliferative
      responses to stimulations with concanavalin A (ConA), lipopolysaccharide (LPS),
      and FMDV antigen, and the numbers of IgG-secreting plasma cells in the bone
      marrow, suggesting that RO/GS-R enhanced both Th1 and Th2 immune responses. In
      addition, no significant difference was found between RO/GS-R and the commercial
      adjuvant oil ISA 206 in the promotion of FMD vaccine-induced immune responses.
      Considering the vegetable origin of RO and GS-R and the potent adjuvant activity,
      RO/GS-R should be studied further for the development of veterinary vaccines,
      especially for use in food animals in order to promote food safety. 

PMID- 24920602
TI  - Role for Gr-1+ cells in the control of high-dose Mycobacterium bovis recombinant
      BCG.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG) is an attractive target for
      development as a live vaccine vector delivering transgenic antigens from HIV and
      other pathogens. Most studies aimed at defining the clearance of BCG have been
      performed at doses between 10(2) and 10(4) CFU. Interestingly, however,
      recombinant BCG (rBCG) administered at doses of >10(6) CFU effectively generates
      antigen-specific T-cell responses and primes for heterologous boost responses.
      Thus, defining clearance at high doses might aid in the optimization of rBCG as a
      vector. In this study, we used bioluminescence imaging to examine the kinetics of
      rBCG transgene expression and clearance in mice immunized with 5 * 10(7) CFU rBCG
      expressing luciferase. Similar to studies using low-dose rBCG, our results
      demonstrate that the adaptive immune response is necessary for long-term control
      of rBCG beginning 9 days after immunizing mice. However, in contrast to these
      reports, we observed that the majority of mycobacterial antigen was eliminated
      prior to day 9. By examining knockout and antibody-mediated depletion mouse
      models, we demonstrate that the rapid clearance of rBCG occurs in the first 24 h
      and is mediated by Gr-1(+) cells. As Gr-1(+) granulocytes have been described as
      having no impact on BCG clearance at low doses, our results reveal an
      unappreciated role for Gr-1(+) neutrophils and inflammatory monocytes in the
      clearance of high-dose rBCG. This work demonstrates the potential of applying
      bioluminescence imaging to rBCG in order to gain an understanding of the immune
      response and increase the efficacy of rBCG as a vaccine vector. 

PMID- 24920603
TI  - A Single B-repeat of Staphylococcus epidermidis accumulation-associated protein
      induces protective immune responses in an experimental biomaterial-associated
      infection mouse model.
AB  - Nosocomial infections are the fourth leading cause of morbidity and mortality in
      the United States, resulting in 2 million infections and ~100,000 deaths each
      year. More than 60% of these infections are associated with some type of
      biomedical device. Staphylococcus epidermidis is a commensal bacterium of the
      human skin and is the most common nosocomial pathogen infecting implanted medical
      devices, especially those in the cardiovasculature. S. epidermidis antibiotic
      resistance and biofilm formation on inert surfaces make these infections hard to
      treat. Accumulation-associated protein (Aap), a cell wall-anchored protein of S.
      epidermidis, is considered one of the most important proteins involved in the
      formation of S. epidermidis biofilm. A small recombinant protein vaccine
      comprising a single B-repeat domain (Brpt1.0) of S. epidermidis RP62A Aap was
      developed, and the vaccine's efficacy was evaluated in vitro with a biofilm
      inhibition assay and in vivo in a murine model of biomaterial-associated
      infection. A high IgG antibody response against S. epidermidis RP62A was detected
      in the sera of the mice after two subcutaneous immunizations with Brpt1.0
      coadministered with Freund's adjuvant. Sera from Brpt1.0-immunized mice inhibited
      in vitro S. epidermidis RP62A biofilm formation in a dose-dependent pattern.
      After receiving two immunizations, each mouse was surgically implanted with a
      porous scaffold disk containing 5 * 10(6) CFU of S. epidermidis RP62A. Weight
      changes, inflammatory markers, and histological assay results after challenge
      with S. epidermidis indicated that the mice immunized with Brpt1.0 exhibited
      significantly higher resistance to S. epidermidis RP62A implant infection than
      the control mice. Day 8 postchallenge, there was a significantly lower number of
      bacteria in scaffold sections and surrounding tissues and a lower residual
      inflammatory response to the infected scaffold disks for the Brpt1.0-immunized
      mice than for of the ovalbumin (Ova)-immunized mice. 

PMID- 24920604
TI  - Tonsils of the soft palate do not mediate the response of pigs to oral
      vaccination with heat-inactivated Mycobacterium bovis.
AB  - Mycobacterium bovis causes animal tuberculosis (TB) in cattle, humans, and other
      mammalian species, including pigs. The goal of this study was to experimentally
      assess the responses of pigs with and without a history of tonsillectomy to oral
      vaccination with heat-inactivated M. bovis and challenge with a virulent M. bovis
      field strain, to compare pig and wild boar responses using the same vaccination
      model as previously used in the Eurasian wild boar (Sus scrofa), to evaluate the
      use of several enzyme-linked immunosorbent assays (ELISAs) and lateral flow tests
      for in vivo TB diagnosis in pigs, and to verify if these tests are influenced by
      oral vaccination with inactivated M. bovis. At necropsy, the lesion and culture
      scores were 20% to 43% higher in the controls than those in the vaccinated pigs.
      Massive M. bovis growth from thoracic tissue samples was observed in 4 out of 9
      controls but in none of the 10 vaccinated pigs. No effect of the presence or
      absence of tonsils was observed on these scores, suggesting that tonsils are not
      involved in the protective response to this vaccine in pigs. The serum antibody
      levels increased significantly only after challenge. At necropsy, the estimated
      sensitivities of the ELISAs and dual path platform (DPP) assays ranged from 89%
      to 94%. In the oral mucosa, no differences in gene expression were observed in
      the control group between the pigs with and without tonsils. In the vaccinated
      group, the mRNA levels for chemokine (C-C motif) receptor 7 (CCR7), interferon
      beta (IFN-beta), and methylmalonyl coenzyme A mutase (MUT) were higher in pigs
      with tonsils. Complement component 3 mRNA levels in peripheral blood mononuclear
      cells (PBMC) increased with vaccination and decreased after M. bovis challenge.
      This information is relevant for pig production in regions that are endemic for
      M. bovis and for TB vaccine research. 

PMID- 24920605
TI  - Eating more red meat is linked with raised risk of breast cancer.

PMID- 24920606
TI  - HIV testing among sexually active Hispanic/Latino MSM in Miami-Dade County and
      New York City: opportunities for increasing acceptance and frequency of testing.
AB  - HIV testing behavior is important in understanding the high rates of undiagnosed
      infection among Hispanic/Latino men who have sex with men (MSM). Correlates of
      repeat/recent testing (within the past year and >=5 tests during lifetime) and
      test avoidance (never or >5 years earlier) were examined among 608 sexually
      active Hispanic/Latino MSM (Miami-Dade County and New York City). Those who
      reported repeat/recent testing were more likely to have incomes over $30,000,
      speak English predominately, and have visited and disclosed same-sex behavior to
      a health care provider (HCP) in the past year. Those who were classified as test
      avoiders were less likely to have incomes over $10,000 and to have seen an HCP in
      the past year. The main reason for not testing (in both groups) was fear of HIV
      positivity; however, twice as many test avoiders considered this their main
      reason, and more test avoiders had confidentiality concerns. Results suggest that
      messages to encourage testing among Hispanic/Latino MSM may be most effective if
      past testing patterns and reasons for not testing are considered. HCPs can play
      an important role by consistently offering HIV tests to MSM and tailoring
      messages based on prior testing histories. 

PMID- 24920607
TI  - Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of
      muscular dystrophies.
AB  - Despite the recent progress in the broad-scaled analysis of proteins in body
      fluids, there is still a lack in protein profiling approaches for biomarkers of
      rare diseases. Scarcity of samples is the main obstacle hindering attempts to
      apply discovery driven protein profiling in rare diseases. We addressed this
      challenge by combining samples collected within the BIO-NMD consortium from four
      geographically dispersed clinical sites to identify protein markers associated
      with muscular dystrophy using an antibody bead array platform with 384
      antibodies. Based on concordance in statistical significance and confirmatory
      results obtained from analysis of both serum and plasma, we identified eleven
      proteins associated with muscular dystrophy, among which four proteins were
      elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3)
      and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch
      muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron
      transfer flavoprotein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles
      correlating with disease progression and severity were identified, which hold
      promise for the development of new clinical tools for management of
      dystrophinopathies. 

PMID- 24920609
TI  - Acute ischaemic stroke or transient ischaemic attack and the need for inpatient
      echocardiography.
AB  - OBJECTIVES: To determine the diagnostic yield of echocardiography and its utility
      in changing medical management; and to derive a risk score to guide its use in
      patients with in-hospital stroke or transient ischaemic attack (TIA). METHODS: We
      carried out a retrospective chart review from January 2009 to June 2010 of
      patients with acute ischaemic stroke or TIA who had undergone transthoracic
      echocardiography (TTE) or transoesophageal echocardiography (TOE). Clinical and
      imaging findings at baseline were noted and 'potential clinically relevant
      findings' identified on TTE and TOE. A multivariable logistic regression was used
      to identify predictors of potential clinically relevant findings on TTE or TOE
      and derive a risk score. RESULTS: Of 370 patients, 307 (83.0%) had TTE and 63
      (17.0%) had additional TOE. Potential clinically relevant findings on
      echocardiography were noted in 28 (7.6%) patients. Change in medical management
      was noted in 19/307 (6.2%) patients on TTE and in 7/63 (11.1%) patients on TOE.
      Male sex (OR 3.05, 95% CI 1.19 to 7.84; p=0.021), abnormal admission ECG (OR
      4.39, 95% CI 1.79 to 10.79; p=0.001), and embolic pattern imaging at baseline (OR
      2.38, 95% CI 1.05 to 5.40; p=0.038) were independent predictors of findings on
      TTE or TOE. A risk score including these three variables had modest
      discrimination (c-statistic 0.69, 95% CI 0.59 to 0.80). CONCLUSIONS:
      Echocardiography detected potential clinically relevant findings in a minority of
      patients (7.6%), but these findings changed medical management 90.5% of the time.
      A risk score using sex, ECG abnormality, and embolic pattern imaging at baseline
      could help predict which patients are more likely to have these echo findings.

PMID- 24920608
TI  - A novel genome-wide in vivo screen for metastatic suppressors in human colon
      cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12.
AB  - The progression of tumors to the metastatic state involves the loss of metastatic
      suppressor functions. Finding these, however, is difficult as in vitro assays do
      not fully predict metastatic behavior, and the majority of studies have used
      cloned cell lines, which do not reflect primary tumor heterogeneity. Here, we
      have designed a novel genome-wide screen to identify metastatic suppressors using
      primary human tumor cells in mice, which allows saturation screens. Using this
      unbiased approach, we have tested the hypothesis that endogenous colon cancer
      metastatic suppressors affect WNT-TCF signaling. Our screen has identified two
      novel metastatic suppressors: TMED3 and SOX12, the knockdown of which increases
      metastatic growth after direct seeding. Moreover, both modify the type of self
      renewing spheroids, but only knockdown of TMED3 also induces spheroid cell
      spreading and lung metastases from a subcutaneous xenograft. Importantly, whereas
      TMED3 and SOX12 belong to different families involved in protein secretion and
      transcriptional regulation, both promote endogenous WNT-TCF activity. Treatments
      for advanced or metastatic colon cancer may thus not benefit from WNT blockers,
      and these may promote a worse outcome. 

PMID- 24920610
TI  - Public communication of science 2.0: Is the communication of science via the "new
      media" online a genuine transformation or old wine in new bottles?

PMID- 24920611
TI  - Beyond eye movements: a role for frontal eye fields in evaluating decisions.

PMID- 24920612
TI  - Dendrites impact the encoding capabilities of the axon.
AB  - This study highlights a new and powerful direct impact of the dendritic tree (the
      input region of neurons) on the encoding capability of the axon (the output
      region). We show that the size of the dendritic arbors (its impedance load)
      strongly modulates the shape of the action potential (AP) onset at the axon
      initial segment; it is accelerated in neurons with larger dendritic surface area.
      AP onset rapidness is key in determining the capability of the axonal spikes to
      encode (phase lock to) rapid changes in synaptic inputs. Hence, our findings
      imply that neurons with larger dendritic arbors have improved encoding
      capabilities. This "dendritic size effect" was explored both analytically as well
      as numerically, in simplified and detailed models of 3D reconstructed layer 2/3
      cortical pyramidal cells of rats and humans. The cutoff frequency of spikes phase
      locking to modulated inputs increased from 100 to 200 Hz in pyramidal cells of
      young rats to 400-600 Hz in human cells. In the latter case, phase locking
      reached close to 1 KHz in in vivo-like conditions. This work highlights new and
      functionally profound cross talk between the dendritic tree and the axon initial
      segment, providing new understanding of neurons as sophisticated nonlinear
      input/output devices. 

PMID- 24920613
TI  - Deficits in predictive coding underlie hallucinations in schizophrenia.
AB  - The neural mechanisms that produce hallucinations and other psychotic symptoms
      remain unclear. Previous research suggests that deficits in predictive signals
      for learning, such as prediction error signals, may underlie psychotic symptoms,
      but the mechanism by which such deficits produce psychotic symptoms remains to be
      established. We used model-based fMRI to study sensory prediction errors in human
      patients with schizophrenia who report daily auditory verbal hallucinations
      (AVHs) and sociodemographically matched healthy control subjects. We manipulated
      participants' expectations for hearing speech at different periods within a
      speech decision-making task. Patients activated a voice-sensitive region of the
      auditory cortex while they experienced AVHs in the scanner and displayed a
      concomitant deficit in prediction error signals in a similar portion of auditory
      cortex. This prediction error deficit correlated strongly with increased activity
      during silence and with reduced volumes of the auditory cortex, two established
      neural phenotypes of AVHs. Furthermore, patients with more severe AVHs had more
      deficient prediction error signals and greater activity during silence within the
      region of auditory cortex where groups differed, regardless of the severity of
      psychotic symptoms other than AVHs. Our findings suggest that deficient
      predictive coding accounts for the resting hyperactivity in sensory cortex that
      leads to hallucinations. 

PMID- 24920615
TI  - Adaptation to vocal expressions reveals multistep perception of auditory emotion.
AB  - The human voice carries speech as well as important nonlinguistic signals that
      influence our social interactions. Among these cues that impact our behavior and
      communication with other people is the perceived emotional state of the speaker.
      A theoretical framework for the neural processing stages of emotional prosody has
      suggested that auditory emotion is perceived in multiple steps (Schirmer and
      Kotz, 2006) involving low-level auditory analysis and integration of the acoustic
      information followed by higher-level cognition. Empirical evidence for this
      multistep processing chain, however, is still sparse. We examined this question
      using functional magnetic resonance imaging and a continuous carry-over design
      (Aguirre, 2007) to measure brain activity while volunteers listened to non-speech
      affective vocalizations morphed on a continuum between anger and fear. Analyses
      dissociated neuronal adaptation effects induced by similarity in perceived
      emotional content between consecutive stimuli from those induced by their
      acoustic similarity. We found that bilateral voice-sensitive auditory regions as
      well as right amygdala coded the physical difference between consecutive stimuli.
      In contrast, activity in bilateral anterior insulae, medial superior frontal
      cortex, precuneus, and subcortical regions such as bilateral hippocampi depended
      predominantly on the perceptual difference between morphs. Our results suggest
      that the processing of vocal affect recognition is a multistep process involving
      largely distinct neural networks. Amygdala and auditory areas predominantly code
      emotion-related acoustic information while more anterior insular and prefrontal
      regions respond to the abstract, cognitive representation of vocal affect. 

PMID- 24920614
TI  - Profilin 1 associates with stress granules and ALS-linked mutations alter stress
      granule dynamics.
AB  - Mutations in the PFN1 gene encoding profilin 1 are a rare cause of familial
      amyotrophic lateral sclerosis (ALS). Profilin 1 is a well studied actin-binding
      protein but how PFN1 mutations cause ALS is unknown. The budding yeast,
      Saccharomyces cerevisiae, has one PFN1 ortholog. We expressed the ALS-linked
      profilin 1 mutant proteins in yeast, demonstrating a loss of protein stability
      and failure to restore growth to profilin mutant cells, without exhibiting gain
      of-function toxicity. This model provides for simple and rapid screening of novel
      ALS-linked PFN1 variants. To gain insight into potential novel roles for profilin
      1, we performed an unbiased, genome-wide synthetic lethal screen with yeast cells
      lacking profilin (pfy1Delta). Unexpectedly, deletion of several stress granule
      and processing body genes, including pbp1Delta, were found to be synthetic lethal
      with pfy1Delta. Mutations in ATXN2, the human ortholog of PBP1, are a known ALS
      genetic risk factor and ataxin 2 is a stress granule component in mammalian
      cells. Given this genetic interaction and recent evidence linking stress granule
      dynamics to ALS pathogenesis, we hypothesized that profilin 1 might also
      associate with stress granules. Here we report that profilin 1 and related
      protein profilin 2 are novel stress granule-associated proteins in mouse primary
      cortical neurons and in human cell lines and that ALS-linked mutations in
      profilin 1 alter stress granule dynamics, providing further evidence for the
      potential role of stress granules in ALS pathogenesis. 

PMID- 24920616
TI  - Specialized pathways from the primate amygdala to posterior orbitofrontal cortex.
AB  - The primate amygdala sends dense projections to posterior orbitofrontal cortex
      (pOFC) in pathways that are critical for processing emotional content, but the
      synaptic mechanisms are not understood. We addressed this issue by investigating
      pathways in rhesus monkeys (Macaca mulatta) from the amygdala to pOFC at the
      level of the system and synapse. Terminations from the amygdala were denser and
      larger in pOFC compared with the anterior cingulate cortex, which is also
      strongly connected with the amygdala. Axons from the amygdala terminated most
      densely in the upper layers of pOFC through large terminals. Most of these
      terminals innervated spines of presumed excitatory neurons and many were
      frequently multisynaptic and perforated, suggesting high synaptic efficacy. These
      amygdalar synapses in pOFC exceeded in size and specialization even
      thalamocortical terminals from the prefrontal-related thalamic mediodorsal
      nucleus to the middle cortical layers, which are thought to be highly efficient
      drivers of cortical neurons. Pathway terminals in the upper layers impinge on the
      apical dendrites of neurons in other layers, suggesting that the robust amygdalar
      projections may also activate neurons in layer 5 that project back to the
      amygdala and beyond to autonomic structures. Among inhibitory neurons, the
      amygdalar pathway innervated preferentially the neurochemical classes of
      calbindin and calretinin neurons in the upper layers of pOFC, which are
      synaptically suited to suppress noise and enhance signals. These features provide
      a circuit mechanism for flexibly shifting focus and adjusting emotional drive in
      processes disrupted in psychiatric disorders, such as phobias and obsessive
      compulsive disorder. 

PMID- 24920617
TI  - Eye movements and the neural basis of context effects on visual sensitivity.
AB  - The effects of context on visual sensitivity are well established (e.g.,
      sensitivity to luminance flicker is substantially higher on mean-gray surrounds
      than on white or black surrounds). The neural mechanisms generating context
      effects, however, remain unresolved. In the absence of direct tests, some
      theories invoke enhancement of edges by lateral inhibition, whereas others rely
      on transients caused by miniature eye movements that maintain fixation. We first
      replicated the luminance results on human observers and found unexpectedly that
      sensitivity to red-green flicker is also affected by surround color, being
      substantially higher on mean-gray surrounds than on red or green surrounds. To
      identify the neural bases of both context effects, we used in vivo
      electrophysiological recordings of primate magnocellular and parvocellular
      ganglion cell responses to luminance and red-green modulations, respectively. To
      test neuronal sensitivity to stationary edge contrast, neuronal responses were
      measured at various distances from the modulation edge against various surrounds.
      We found no evidence of enhanced responses to stationary edges on any surrounds,
      ruling out lateral inhibition-type explanations. To simulate the effects of eye
      movements, target patches were abruptly displaced while measuring responses.
      Abruptly displaced edges evoked vigorous transient responses that were selective
      for modulation-phase on mean-gray surrounds, but were phase-invariant on other
      surrounds. Eye movements could thus enhance detection of flicker on mean-gray
      surrounds, and neurometric analyses supported a primary role for eye movements in
      enhancing sensitivity. In addition, the transformation of spatial edges to
      transient neuronal responses by eye movements provides the signals for detecting
      luminance and color edges in natural scenes. 

PMID- 24920618
TI  - Parallel midbrain microcircuits perform independent temporal transformations.
AB  - The capacity to select the most important information and suppress distracting
      information is crucial for survival. The midbrain contains a network critical for
      the selection of the strongest stimulus for gaze and attention. In avians, the
      optic tectum (OT; called the superior colliculus in mammals) and the GABAergic
      nucleus isthmi pars magnocellularis (Imc) cooperate in the selection process. In
      the chicken, OT layer 10, located in intermediate layers, responds to afferent
      input with gamma periodicity (25-75 Hz), measured at the level of individual
      neurons and the local field potential. In contrast, Imc neurons, which receive
      excitatory input from layer 10 neurons, respond with tonic, unusually high
      discharge rates (>150 spikes/s). In this study, we reveal the source of this high
      rate inhibitory activity: layer 10 neurons that project to the Imc possess
      specialized biophysical properties that enable them to transform afferent drive
      into high firing rates (~130 spikes/s), whereas neighboring layer 10 neurons,
      which project elsewhere, transform afferent drive into lower-frequency, periodic
      discharge patterns. Thus, the intermediate layers of the OT contain parallel,
      intercalated microcircuits that generate different temporal patterns of activity
      linked to the functions of their respective downstream targets.

PMID- 24920619
TI  - Suppression of microglial activation is neuroprotective in a mouse model of human
      retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a photoreceptor-degenerative disease caused by
      various mutations and is characterized by death of rod photoreceptor cell
      followed by gradual death of cone photoreceptors. The molecular mechanisms that
      lead to rod and cone death are not yet fully understood. Neuroinflammation
      contributes to the progression of many chronic neurodegenerative disorders.
      However, it remains to be determined how microglia contribute to photoreceptor
      disruption in RP. In this study, we explored the role of microglia as a
      contributor to photoreceptor degeneration in the rd10 mouse model of RP. First,
      we demonstrated that microglia activation was an early alteration in RP retinas.
      Inhibition of microglia activation by minocycline reduced photoreceptor apoptosis
      and significantly improved retinal structure and function and visual behavior in
      rd10 mice. Second, we identified that minocycline exerted its neuroprotective
      effects through both anti-inflammatory and anti-apoptotic mechanisms. Third, we
      found that Cx3cr1 deficiency dysregulated microglia activation and subsequently
      resulted in increased photoreceptor vulnerability in rd10 mice, suggesting that
      the Cx3cl1/Cx3cr1 signaling pathway might protect against microglia
      neurotoxicity. We concluded that suppression of neuroinflammatory responses could
      be a potential treatment strategy aimed at improving photoreceptor survival in
      human RP. 

PMID- 24920620
TI  - Identification and characterization of GABA(A) receptor autoantibodies in
      autoimmune encephalitis.
AB  - Autoimmune forms of encephalitis have been associated with autoantibodies against
      synaptic cell surface antigens such as NMDA- and AMPA-type glutamate receptors,
      GABA(B) receptor, and LGI1. However, it remains unclear how many synaptic
      autoantigens are yet to be defined. Using immunoproteomics, we identified
      autoantibodies against the GABA(A) receptor in human sera from two patients
      diagnosed with encephalitis who presented with cognitive impairment and
      multifocal brain MRI abnormalities. Both patients had antibodies directed against
      the extracellular epitope of the beta3 subunit of the GABA(A) receptor. The beta3
      subunit-containing GABA(A) receptor was a major target of the patients' serum
      antibodies in rat hippocampal neurons because the serum reactivity to the
      neuronal surface was greatly decreased by 80% when the beta3 subunit was knocked
      down. Our developed multiplex ELISA testing showed that both patients had similar
      levels of GABA(A) receptor antibodies, one patient also had a low level of LGI1
      antibodies, and the other also had CASPR2 antibodies. Application of the
      patients' serum at the time of symptom presentation of encephalitis to rat
      hippocampal neuron cultures specifically decreased both synaptic and surface
      GABA(A) receptors. Furthermore, treatment of neurons with the patients' serum
      selectively reduced miniature IPSC amplitude and frequency without affecting
      miniature EPSCs. These results strongly suggest that the patients' GABA(A)
      receptor antibodies play a central role in the patients' symptoms. Therefore,
      this study establishes anti-GABA(A) receptor encephalitis and expands the
      pathogenic roles of GABA(A) receptor autoantibodies.

PMID- 24920621
TI  - Submembrane assembly and renewal of rod photoreceptor cGMP-gated channel: insight
      into the actin-dependent process of outer segment morphogenesis.
AB  - The photoreceptor outer segment (OS) is comprised of two compartments: plasma
      membrane (PM) and disk membranes. It is unknown how the PM renewal is coordinated
      with that of the disk membranes. Here we visualized the localization and
      trafficking process of rod cyclic nucleotide-gated channel alpha-subunit (CNGA1),
      a PM component essential for phototransduction. The localization was visualized
      by fusing CNGA1 to a fluorescent protein Dendra2 and expressing in Xenopus laevis
      rod photoreceptors. Dendra2 allowed us to label CNGA1 in a spatiotemporal manner
      and therefore discriminate between old and newly trafficked CNGA1-Dendra2 in the
      OS PM. Newly synthesized CNGA1 was preferentially trafficked to the basal region
      of the lateral OS PM where newly formed and matured disks are also added. Unique
      trafficking pattern and diffusion barrier excluded CNGA1 from the PM domains,
      which are the proposed site of disk membrane maturation. Such distinct
      compartmentalization allows the confinement of cyclic nucleotide-gated channel in
      the PM, while preventing the disk membrane incorporation. Cytochalasin D and
      latrunculin A treatments, which are known to disrupt F-actin-dependent disk
      membrane morphogenesis, prevented the entrance of newly synthesized CNGA1 to the
      OS PM, but did not prevent the entrance of rhodopsin and peripherin/rds to the
      membrane evaginations believed to be disk membrane precursors. Uptake of
      rhodopsin and peripherin/rds coincided with the overgrowth of the evaginations at
      the base of the OS. Thus F-actin is essential for the trafficking of CNGA1 to the
      ciliary PM, and coordinates the formations of disk membrane rim region and OS PM.

PMID- 24920622
TI  - Conditional ablation of astroglial CCL2 suppresses CNS accumulation of M1
      macrophages and preserves axons in mice with MOG peptide EAE.
AB  - Current multiple sclerosis (MS) therapies only partially prevent chronically
      worsening neurological deficits, which are largely attributable to progressive
      loss of CNS axons. Prior studies of experimental autoimmune encephalomyelitis
      (EAE) induced in C57BL/6 mice by immunization with myelin oligodendrocyte
      glycoprotein peptide 35-55 (MOG peptide), a model of MS, documented continued
      axon loss for months after acute CNS inflammatory infiltrates had subsided, and
      massive astroglial induction of CCL2 (MCP-1), a chemokine for CCR2(+) monocytes.
      We now report that conditional deletion of astroglial CCL2 significantly
      decreases CNS accumulation of classically activated (M1) monocyte-derived
      macrophages and microglial expression of M1 markers during the initial CNS
      inflammatory phase of MOG peptide EAE, reduces the acute and long-term severity
      of clinical deficits and slows the progression of spinal cord axon loss. In
      addition, lack of astroglial-derived CCL2 results in increased accumulation of
      Th17 cells within the CNS in these mice, but also in greater confinement of
      CD4(+) lymphocytes to CNS perivascular spaces. These findings suggest that
      therapies designed to inhibit astroglial CCL2-driven trafficking of monocyte
      derived macrophages to the CNS during acute MS exacerbations have the potential
      to significantly reduce CNS axon loss and slow progression of neurological
      deficits. 

PMID- 24920623
TI  - Astrocyte-derived BDNF supports myelin protein synthesis after cuprizone-induced
      demyelination.
AB  - It is well established that BDNF may enhance oligodendrocyte differentiation
      following a demyelinating lesion, however, the endogenous sources of BDNF that
      may be harnessed to reverse deficits associated with such lesions are poorly
      defined. Here, we investigate roles of astrocytes in synthesizing and releasing
      BDNF. These cells are known to express BDNF following injury in vivo. In culture,
      they increase BDNF synthesis and release in response to glutamate metabotropic
      stimulation. Following cuprizone-elicited demyelination in mice, astrocytes
      contain BDNF and increase levels of metabotropic receptors. The metabotropic
      agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), was
      therefore injected into the demyelinating lesion. Increases in BDNF, as well as
      myelin proteins, were observed. Effects of ACPD were eliminated by coinjection of
      trkB-Fc to locally deplete BDNF and by deletion of astrocyte-derived BDNF. The
      data indicate that astrocyte-derived BDNF may be a source of trophic support that
      can be used to reverse deficits elicited following demyelination. 

PMID- 24920624
TI  - Synaptic properties of SOM- and CCK-expressing cells in dentate gyrus interneuron
      networks.
AB  - Hippocampal GABAergic cells are highly heterogeneous, but the functional
      significance of this diversity is not fully understood. By using paired
      recordings of synaptically connected interneurons in slice preparations of the
      rat and mouse dentate gyrus (DG), we show that morphologically identified
      interneurons form complex neuronal networks. Synaptic inhibitory interactions
      exist between cholecystokinin (CCK)-expressing hilar commissural associational
      path (HICAP) cells and among somatostatin (SOM)-containing hilar perforant path
      associated (HIPP) interneurons. Moreover, both interneuron types inhibit
      parvalbumin (PV)-expressing perisomatic inhibitory basket cells (BCs), whereas
      BCs and HICAPs rarely target HIPP cells. HICAP and HIPP cells produce slow, weak,
      and unreliable inhibition onto postsynaptic interneurons. The time course of
      inhibitory signaling is defined by the identity of the presynaptic and
      postsynaptic cell. It is the slowest for HIPP-HIPP, intermediately slow for HICAP
      HICAP, but fast for BC-BC synapses. GABA release at interneuron-interneuron
      synapses also shows cell type-specific short-term dynamics, ranging from multiple
      pulse facilitation at HICAP-HICAP, biphasic modulation at HIPP-HIPP to depression
      at BC-BC synapses. Although dendritic inhibition at HICAP-BC and HIPP-BC synapses
      appears weak and slow, channelrhodopsin 2-mediated excitation of SOM terminals
      demonstrates that they effectively control the activity of target interneurons.
      They markedly reduce the discharge probability but sharpen the temporal precision
      of action potential generation. Thus, dendritic inhibition seems to play an
      important role in determining the activity pattern of GABAergic interneuron
      populations and thereby the flow of information through the DG circuitry. 

PMID- 24920625
TI  - Is Parkinson's disease a vesicular dopamine storage disorder? Evidence from a
      study in isolated synaptic vesicles of human and nonhuman primate striatum.
AB  - The cause of degeneration of nigrostriatal dopamine (DA) neurons in idiopathic
      Parkinson's disease (PD) is still unknown. Intraneuronally, DA is largely
      confined to synaptic vesicles where it is protected from metabolic breakdown. In
      the cytoplasm, however, free DA can give rise to formation of cytotoxic free
      radicals. Normally, the concentration of cytoplasmic DA is kept at a minimum by
      continuous pumping activity of the vesicular monoamine transporter (VMAT)2.
      Defects in handling of cytosolic DA by VMAT2 increase levels of DA-generated oxy
      radicals ultimately resulting in degeneration of DAergic neurons. Here, we
      isolated for the first time, DA storage vesicles from the striatum of six
      autopsied brains of PD patients and four controls and measured several indices of
      vesicular DA storage mechanisms. We found that (1) vesicular uptake of DA and
      binding of the VMAT2-selective label [(3)H]dihydrotetrabenazine were profoundly
      reduced in PD by 87-90% and 71-80%, respectively; (2) after correcting for DA
      nerve terminal loss, DA uptake per VMAT2 transport site was significantly reduced
      in PD caudate and putamen by 53 and 55%, respectively; (3) the VMAT2 transport
      defect appeared specific for PD as it was not present in Macaca fascicularis (7
      MPTP and 8 controls) with similar degree of MPTP-induced nigrostriatal
      neurodegeneration; and (4) DA efflux studies and measurements of acidification in
      the vesicular preparations suggest that the DA storage impairment was localized
      at the VMAT2 protein itself. We propose that this VMAT2 defect may be an early
      abnormality promoting mechanisms leading to nigrostriatal DA neuron death in PD. 

PMID- 24920626
TI  - Role of small conductance Ca2+-activated K+ channels in controlling CA1 pyramidal
      cell excitability.
AB  - Small-conductance Ca(2+)-activated K(+) (SK or K(Ca)2) channels are widely
      expressed in the CNS. In several types of neurons, these channels were shown to
      become activated during repetitive firing, causing early spike frequency
      adaptation. In CA1 pyramidal cells, SK channels in dendritic spines were shown to
      regulate synaptic transmission. However, the presence of functional SK channels
      in the somata and their role in controlling the intrinsic firing of these neurons
      has been controversial. Using whole-cell voltage-clamp and current-clamp
      recordings in acute hippocampal slices and focal applications of irreversible and
      reversible SK channel blockers, we provide evidence that functional SK channels
      are expressed in the somata and proximal dendrites of adult rat CA1 pyramidal
      cells. Although these channels can generate a medium duration
      afterhyperpolarizing current, they play only an auxiliary role in controlling the
      intrinsic excitability of these neurons, secondary to the low voltage-activating,
      noninactivating K(V)7/M channels. As long as K(V)7/M channels are operative,
      activation of SK channels during repetitive firing does not notably affect the
      spike output of CA1 pyramidal cells. However, when K(V)7/M channel activity is
      compromised, SK channel activation significantly and uniquely reduces spike
      output of these neurons. Therefore, proximal SK channels provide a "second line
      of defense" against intrinsic hyperexcitability, which may play a role in
      multiple conditions in which K(V)7/M channels activity is compromised, such as
      hyposmolarity.

PMID- 24920628
TI  - The basal thermal sensitivity of the TRPV1 ion channel is determined by
      PKCbetaII.
AB  - Peripheral nociceptors are excited by the activation of membrane receptors and
      ion channels. The heat-sensitive TRPV1 ion channel responds to various noxious
      chemical and thermal stimuli, causing pain and itch. Here, we show that TRPV1 is
      coexpressed with PKCbetaII in a subset of mouse sensory neurons and that, in
      these neurons, TRPV1 binds directly to PKCbetaII, leading to the activation and
      translocation of PKCbetaII. Activated PKCbetaII, in turn, significantly increases
      the responsiveness of TRPV1 by phosphorylating Thr705. The heat sensitivity of
      TRPV1 is almost eliminated by either knocking down PKCbetaII or mutating Thr705;
      however, neither of these manipulations affects the potentiation of TRPV1 caused
      by the activation of PKCepsilon. PKCbetaII thus acts as an auxiliary subunit of
      TRPV1 by forming a population-dependent TRPV1 ion channel complex controlling the
      sensitivity of TRPV1 and setting the threshold for pain and itch. 

PMID- 24920627
TI  - Cerebellar zonal patterning relies on Purkinje cell neurotransmission.
AB  - Cerebellar circuits are patterned into an array of topographic parasagittal
      domains called zones. The proper connectivity of zones is critical for motor
      coordination and motor learning, and in several neurological diseases cerebellar
      circuits degenerate in zonal patterns. Despite recent advances in understanding
      zone function, we still have a limited understanding of how zones are formed.
      Here, we focused our attention on Purkinje cells to gain a better understanding
      of their specific role in establishing zonal circuits. We used conditional mouse
      genetics to test the hypothesis that Purkinje cell neurotransmission is essential
      for refining prefunctional developmental zones into sharp functional zones. Our
      results show that inhibitory synaptic transmission in Purkinje cells is necessary
      for the precise patterning of Purkinje cell zones and the topographic targeting
      of mossy fiber afferents. As expected, blocking Purkinje cell neurotransmission
      caused ataxia. Using in vivo electrophysiology, we demonstrate that loss of
      Purkinje cell communication altered the firing rate and pattern of their target
      cerebellar nuclear neurons. Analysis of Purkinje cell complex spike firing
      revealed that feedback in the cerebellar nuclei to inferior olive to Purkinje
      cell loop is obstructed. Loss of Purkinje neurotransmission also caused ectopic
      zonal expression of tyrosine hydroxylase, which is only expressed in adult
      Purkinje cells when calcium is dysregulated and if excitability is altered. Our
      results suggest that Purkinje cell inhibitory neurotransmission establishes the
      functional circuitry of the cerebellum by patterning the molecular zones, fine
      tuning afferent circuitry, and shaping neuronal activity. 

PMID- 24920629
TI  - Ischemic stroke injury is mediated by aberrant Cdk5.
AB  - Ischemic stroke is one of the leading causes of morbidity and mortality.
      Treatment options are limited and only a minority of patients receive acute
      interventions. Understanding the mechanisms that mediate neuronal injury and
      death may identify targets for neuroprotective treatments. Here we show that the
      aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal
      death in rodents during stroke. Ischemia induced either by embolic middle
      cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in
      brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor
      p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine
      neurotransmission, maintained field potentials, and blocked excitotoxicity.
      Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5
      prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically
      reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may
      serve as an effective treatment for stroke. 

PMID- 24920630
TI  - Wnt-responsive Lgr5+ globose basal cells function as multipotent olfactory
      epithelium progenitor cells.
AB  - Persistent neurogenesis in the olfactory epithelium provides a unique model to
      study neural stem cell self-renewal and fate determination. In the olfactory
      neuroepithelium, globose basal cells (GBCs) are considered to be the direct
      progenitors of olfactory neurons. However, the study of neurogenesis from GBCs
      has been impeded by the paucity of GBC-specific markers. Here we report that
      Lgr5, a recently discovered adult stem cell marker, is exclusively expressed in
      GBCs in neonatal and adult mice. Lgr5(+) cells display characteristics of cycling
      stem cells, including Ki67 expression and EdU incorporation. Lineage tracing
      analysis demonstrates that Lgr5(+) GBCs regenerate multiple cell types under
      normal turnover condition or after olfactory lesion. Furthermore, upregulation or
      downregulation of Wnt signaling in vivo indicates a key role of Wnt signaling not
      only in maintaining Lgr5(+) cell proliferation and promoting neuroregeneration,
      but also in delaying sensory neuron maturation. Together, our observations
      provided new insights into the dynamics of neurogenesis in the olfactory
      epithelium. 

PMID- 24920631
TI  - Chronic GluN2B antagonism disrupts behavior in wild-type mice without protecting
      against synapse loss or memory impairment in Alzheimer's disease mouse models.
AB  - Extensive evidence implicates GluN2B-containing NMDA receptors (GluN2B-NMDARs) in
      excitotoxic-insult-induced neurodegeneration and amyloid beta (Abeta)-induced
      synaptic dysfunction. Therefore, inhibiting GluN2B-NMDARs would appear to be a
      potential therapeutic strategy to provide neuroprotection and improve cognitive
      function in Alzheimer's disease (AD). However, there are no reports of long-term
      in vivo treatment of AD mouse models with GluN2B antagonists. We used
      piperidine18 (Pip18), a potent and selective GluN2B-NMDAR antagonist with
      favorable pharmacokinetic properties, for long-term dosing in AD mouse models.
      Reduced freezing behavior in Tg2576 mice during fear conditioning was partially
      reversed after subchronic (17 d) Pip18 treatment. However, analysis of freezing
      behavior in different contexts indicated that this increased freezing likely
      involves elevated anxiety or excessive memory generalization in both
      nontransgenic (NTG) and Tg2576 mice. In PS2APP mice chronically fed with
      medicated food containing Pip18 for 4 months, spatial learning and memory
      deficits were not rescued, plaque-associated spine loss was not affected, and
      synaptic function was not altered. At the same time, altered open field activity
      consistent with increased anxiety and degraded performance in an active avoidance
      task were observed in NTG after chronic treatment. These results indicate that
      long-term treatment with a GluN2B-NMDAR antagonist does not provide a disease
      modifying benefit and could cause cognitive liabilities rather than symptomatic
      benefit in AD mouse models. Therefore, these results challenge the expectation of
      the therapeutic potential for GluN2B-NMDAR antagonists in AD. 

PMID- 24920632
TI  - Learning redundant motor tasks with and without overlapping dimensions:
      facilitation and interference effects.
AB  - Prior learning of a motor skill creates motor memories that can facilitate or
      interfere with learning of new, but related, motor skills. One hypothesis of
      motor learning posits that for a sensorimotor task with redundant degrees of
      freedom, the nervous system learns the geometric structure of the task and
      improves performance by selectively operating within that task space. We tested
      this hypothesis by examining if transfer of learning between two tasks depends on
      shared dimensionality between their respective task spaces. Human participants
      wore a data glove and learned to manipulate a computer cursor by moving their
      fingers. Separate groups of participants learned two tasks: a prior task that was
      unique to each group and a criterion task that was common to all groups. We
      manipulated the mapping between finger motions and cursor positions in the prior
      task to define task spaces that either shared or did not share the task space
      dimensions (x-y axes) of the criterion task. We found that if the prior task
      shared task dimensions with the criterion task, there was an initial facilitation
      in criterion task performance. However, if the prior task did not share task
      dimensions with the criterion task, there was prolonged interference in learning
      the criterion task due to participants finding inefficient task solutions. These
      results show that the nervous system learns the task space through practice, and
      that the degree of shared task space dimensionality influences the extent to
      which prior experience transfers to subsequent learning of related motor skills. 

PMID- 24920633
TI  - Gephyrin clusters are absent from small diameter primary afferent terminals
      despite the presence of GABA(A) receptors.
AB  - Whereas both GABA(A) receptors (GABA(A)Rs) and glycine receptors (GlyRs) play a
      role in control of dorsal horn neuron excitability, their relative contribution
      to inhibition of small diameter primary afferent terminals remains controversial.
      To address this, we designed an approach for quantitative analyses of the
      distribution of GABA(A)R-subunits, GlyR alpha1-subunit and their anchoring
      protein, gephyrin, on terminals of rat spinal sensory afferents identified by
      Calcitonin-Gene-Related-Peptide (CGRP) for peptidergic terminals, and by
      Isolectin-B4 (IB4) for nonpeptidergic terminals. The approach was designed for
      light microscopy, which is compatible with the mild fixation conditions necessary
      for immunodetection of several of these antigens. An algorithm was designed to
      recognize structures with dimensions similar to those of the microscope
      resolution. To avoid detecting false colocalization, the latter was considered
      significant only if the degree of pixel overlap exceeded that expected from
      randomly overlapping pixels given a hypergeometric distribution. We found that
      both CGRP(+) and IB4(+) terminals were devoid of GlyR alpha1-subunit and
      gephyrin. The alpha1 GABA(A)R was also absent from these terminals. In contrast,
      the GABA(A)R alpha2/alpha3/alpha5 and beta3 subunits were significantly expressed
      in both terminal types, as were other GABA(A)R-associated-proteins (alpha
      Dystroglycan/Neuroligin-2/Collybistin-2). Ultrastructural immunocytochemistry
      confirmed the presence of GABA(A)R beta3 subunits in small afferent terminals.
      Real-time quantitative PCR (qRT-PCR) confirmed the results of light microscopy
      immunochemical analysis. These results indicate that dorsal horn inhibitory
      synapses follow different rules of organization at presynaptic versus
      postsynaptic sites (nociceptive afferent terminals vs inhibitory synapses on
      dorsal horn neurons). The absence of gephyrin clusters from primary afferent
      terminals suggests a more diffuse mode of GABA(A)-mediated transmission at
      presynaptic than at postsynaptic sites.

PMID- 24920634
TI  - Reducing glypican-4 in ES cells improves recovery in a rat model of Parkinson's
      disease by increasing the production of dopaminergic neurons and decreasing
      teratoma formation.
AB  - The heparan sulfate proteoglycan Glypican 4 (Gpc4) is strongly expressed in mouse
      embryonic stem (ES) cells where it controls the maintenance of self-renewal by
      modulating Wnt/beta-catenin signaling activities. Here we show that mouse ES
      cells carrying a hypomorphic Gpc4 allele, in a single-step neuronal
      differentiation protocol, show increased differentiation into dopaminergic
      neurons expressing tyrosine hydroxylase (TH) and nuclear receptor related-1
      protein (Nurr1) 1. In contrast to wild-type cells, these differentiating Gpc4
      mutant cells expressed high levels of DOPA decarboxylase and the dopamine
      transporter, two markers expressed by fully mature dopaminergic neurons.
      Intrastriatal transplantation of Gpc4 hypomorphic cells into a 6-OHDA rat model
      for Parkinson's disease improved motor behavior in the cylinder test and
      amphetamine-induced rotations at a higher level than transplanted wild-type
      cells. Importantly, Gpc4 hypomorphic cell grafts, in contrast to wild-type cells,
      did not generate teratomas in the host brains, leading to strongly enhanced
      animal survival. Therefore, control of Gpc4 activity level represents a new
      potential strategy to reduce ES cell tumorigenic features while at the same time
      increasing neuronal differentiation and integration. 

PMID- 24920636
TI  - Anomalous transfer of syntax between languages.
AB  - Each human language possesses a set of distinctive syntactic rules. Here, we show
      that balanced Welsh-English bilinguals reading in English unconsciously apply a
      morphosyntactic rule that only exists in Welsh. The Welsh soft mutation rule
      determines whether the initial consonant of a noun changes based on the
      grammatical context (e.g., the feminine noun cath--"cat" mutates into gath in the
      phrase y gath--"the cat"). Using event-related brain potentials, we establish
      that English nouns artificially mutated according to the Welsh mutation rule
      (e.g., "goncert" instead of "concert") require significantly less processing
      effort than the same nouns implicitly violating Welsh syntax. Crucially, this
      effect is found whether or not the mutation affects the same initial consonant in
      English and Welsh, showing that Welsh syntax is applied to English regardless of
      phonological overlap between the two languages. Overall, these results
      demonstrate for the first time that abstract syntactic rules transfer anomalously
      from one language to the other, even when such rules exist only in one language.

PMID- 24920635
TI  - Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely
      modulate evoked glutamate separately from spontaneous glutamate transmission.
AB  - Action potentials trigger synaptic terminals to synchronously release vesicles,
      but some vesicles release spontaneously. G-protein-coupled receptors (GPCRs) can
      modulate both of these processes. At cranial primary afferent terminals, the GPCR
      cannabinoid 1 (CB1) is often coexpressed with transient receptor potential
      vanilloid 1 (TRPV1), a nonselective cation channel present on most afferents.
      Here we tested whether CB1 activation modulates synchronous, action potential
      evoked (eEPSCs) and/or spontaneous (sEPSCs) EPSCs at solitary tract nucleus
      neurons. In rat horizontal brainstem slices, activation of solitary tract (ST)
      primary afferents generated ST-eEPSCs that were rapidly and reversibly inhibited
      from most afferents by activation of CB1 with arachidonyl-2'-chloroethylamide
      (ACEA) or WIN 55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4
      morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl)
      methanone monomethanesulfonate]. The CB1 antagonist/inverse agonist AM251 [N-1
      (2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3
      carboxamide] blocked these responses. Despite profound depression of ST-eEPSCs
      during CB1 activation, sEPSCs in these same neurons were unaltered. Changes in
      temperature changed sEPSC frequency only from TRPV1(+) afferents (i.e., thermal
      sEPSC responses only occurred in TRPV1(+) afferents). CB1 activation failed to
      alter these thermal sEPSC responses. However, the endogenous arachidonate
      metabolite N-arachidonyldopamine (NADA) promiscuously activated both CB1 and
      TRPV1 receptors. NADA inhibited ST-eEPSCs while simultaneously increasing sEPSC
      frequency, and thermally triggered sEPSC increases in neurons with TRPV1(+)
      afferents. We found no evidence for CB1/TRPV1 interactions suggesting independent
      regulation of two separate vesicle pools. Together, these data demonstrate that
      action potential-evoked synchronous glutamate release is modulated separately
      from TRPV1-mediated glutamate release despite coexistence in the same central
      terminations. This two-pool arrangement allows independent and opposite
      modulation of glutamate release by single lipid metabolites. 

PMID- 24920637
TI  - CNS amyloid-beta, soluble APP-alpha and -beta kinetics during BACE inhibition.
AB  - BACE, a beta-secretase, is an attractive potential disease-modifying therapeutic
      strategy for Alzheimer's disease (AD) as it results directly in the decrease of
      amyloid precursor protein (APP) processing through the beta-secretase pathway and
      a lowering of CNS amyloid-beta (Abeta) levels. The interaction of the beta
      secretase and alpha-secretase pathway-mediated processing of APP in the rhesus
      monkey (nonhuman primate; NHP) CNS is not understood. We hypothesized that CNS
      inhibition of BACE would result in decreased newly generated Abeta and soluble
      APPbeta (sAPPbeta), with increased newly generated sAPPalpha. A stable isotope
      labeling kinetics experiment in NHPs was performed with a (13)C6-leucine infusion
      protocol to evaluate effects of BACE inhibition on CNS APP processing by
      measuring the kinetics of sAPPalpha, sAPPbeta, and Abeta in CSF. Each NHP
      received a low, medium, or high dose of MBI-5 (BACE inhibitor) or vehicle in a
      four-way crossover design. CSF sAPPalpha, sAPPbeta, and Abeta were measured by
      ELISA and newly incorporated label following immunoprecipitation and liquid
      chromatography-mass spectrometry. Concentrations, kinetics, and amount of newly
      generated APP fragments were calculated. sAPPbeta and sAPPalpha kinetics were
      similar, but both significantly slower than Abeta. BACE inhibition resulted in
      decreased labeled sAPPbeta and Abeta in CSF, without observable changes in
      labeled CSF sAPPalpha. ELISA concentrations of sAPPbeta and Abeta both decreased
      and sAPPalpha increased. sAPPalpha increased by ELISA, with no difference by
      labeled sAPPalpha kinetics indicating increases in product may be due to APP
      shunting from the beta-secretase to the alpha-secretase pathway. These results
      provide a quantitative understanding of pharmacodynamic effects of BACE
      inhibition on NHP CNS, which can inform about target development. 

PMID- 24920638
TI  - Statistics of the vestibular input experienced during natural self-motion:
      implications for neural processing.
AB  - It is widely believed that sensory systems are optimized for processing stimuli
      occurring in the natural environment. However, it remains unknown whether this
      principle applies to the vestibular system, which contributes to essential brain
      functions ranging from the most automatic reflexes to spatial perception and
      motor coordination. Here we quantified, for the first time, the statistics of
      natural vestibular inputs experienced by freely moving human subjects during
      typical everyday activities. Although previous studies have found that the power
      spectra of natural signals across sensory modalities decay as a power law (i.e.,
      as 1/f(alpha)), we found that this did not apply to natural vestibular stimuli.
      Instead, power decreased slowly at lower and more rapidly at higher frequencies
      for all motion dimensions. We further establish that this unique stimulus
      structure is the result of active motion as well as passive biomechanical
      filtering occurring before any neural processing. Notably, the transition
      frequency (i.e., frequency at which power starts to decrease rapidly) was lower
      when subjects passively experienced sensory stimulation than when they actively
      controlled stimulation through their own movement. In contrast to signals
      measured at the head, the spectral content of externally generated (i.e.,
      passive) environmental motion did follow a power law. Specifically,
      transformations caused by both motor control and biomechanics shape the
      statistics of natural vestibular stimuli before neural processing. We suggest
      that the unique structure of natural vestibular stimuli will have important
      consequences on the neural coding strategies used by this essential sensory
      system to represent self-motion in everyday life. 

PMID- 24920639
TI  - Specialized postsynaptic morphology enhances neurotransmitter dilution and high
      frequency signaling at an auditory synapse.
AB  - Sensory processing in the auditory system requires that synapses, neurons, and
      circuits encode information with particularly high temporal and spectral
      precision. In the amphibian papillia, sound frequencies up to 1 kHz are encoded
      along a tonotopic array of hair cells and transmitted to afferent fibers via
      fast, repetitive synaptic transmission, thereby promoting phase locking between
      the presynaptic and postsynaptic cells. Here, we have combined serial section
      electron microscopy, paired electrophysiological recordings, and Monte Carlo
      diffusion simulations to examine novel mechanisms that facilitate fast synaptic
      transmission in the inner ear of frogs (Rana catesbeiana and Rana pipiens). Three
      dimensional anatomical reconstructions reveal specialized spine-like contacts
      between individual afferent fibers and hair cells that are surrounded by large,
      open regions of extracellular space. Morphologically realistic diffusion
      simulations suggest that these local enlargements in extracellular space speed
      transmitter clearance and reduce spillover between neighboring synapses, thereby
      minimizing postsynaptic receptor desensitization and improving sensitivity during
      prolonged signal transmission. Additionally, evoked EPSCs in afferent fibers are
      unaffected by glutamate transporter blockade, suggesting that transmitter
      diffusion and dilution, and not uptake, play a primary role in speeding
      neurotransmission and ensuring fidelity at these synapses. 

PMID- 24920640
TI  - Orientation decoding in human visual cortex: new insights from an unbiased
      perspective.
AB  - The development of multivariate pattern analysis or brain "decoding" methods has
      substantially altered the field of fMRI research. Although these methods are
      highly sensitive to whether or not decodable information exists, the information
      they discover and make use of for decoding is often concealed within complex
      patterns of activation. This opacity of interpretation is embodied in influential
      studies showing that the orientation of visual gratings can be decoded from brain
      activity in human visual cortex with fMRI. Although these studies provided a
      compelling demonstration of the power of these methods, their findings were
      somewhat mysterious as the scanning resolution was insufficient to resolve
      orientation columns, i.e., orientation information should not have been
      accessible. Two theories have been put forth to account for this result, the
      hyperacuity account and the biased map account, both of which assume that small
      biases in fMRI voxels are the source of decodable information. In the present
      study, we use Hubel and Wiesel's (1972) classic ice-cube model of visual cortex
      to show that the orientation of gratings can be decoded from an unbiased
      representation. In our analysis, we identify patterns of activity elicited by the
      edges of the stimulus as the source of the decodable information. Furthermore,
      these activation patterns masquerade as a radial bias, a key element of the
      biased map account. This classic model thus sheds new light on the mystery behind
      orientation decoding by unveiling a new source of decodable information. 

PMID- 24920641
TI  - External validation of a multiplex urinary protein panel for the detection of
      bladder cancer in a multicenter cohort.
AB  - BACKGROUND: Because of the faltering sensitivity and/or specificity, urine-based
      assays currently have a limited role in the management of patients with bladder
      cancer. The aim of this study was to externally validate our previously reported
      protein biomarker panel from multiple sites in the United States and Europe.
      METHODS: This multicenter external validation study included a total of 320
      subjects (bladder cancer = 183). The 10 biomarkers (IL8, MMP9, MMP10, SERPINA1,
      VEGFA, ANG, CA9, APOE, SDC1, and SERPINE1) were measured using commercial ELISA
      assays in an external laboratory. The diagnostic performance of the biomarker
      panel was assessed using receiver operator curves (ROC) and descriptive
      statistical values. RESULTS: Utilizing the combination of all 10 biomarkers, the
      area under the ROC for the diagnostic panel was noted to be 0.847 (95% confidence
      interval, 0.796-0.899), outperforming any single biomarker. The multiplex assay
      at optimal cutoff value achieved an overall sensitivity of 0.79, specificity of
      0.79, positive prediction value of 0.73, and negative prediction value of 0.84
      for bladder cancer classification. Sensitivity values of the diagnostic panel for
      high-grade bladder cancer, low-grade bladder cancer, muscle invasive bladder
      cancer, and non-muscle invasive bladder cancer were 0.81, 0.90, 0.95, and 0.77,
      respectively. CONCLUSIONS: Urinary levels of the biomarker panel enabled
      discrimination of patients with bladder cancer and controls, and the levels of
      biomarker subsets were associated with advancing tumor grade and stage. IMPACT:
      If proven to be reliable, urinary diagnostic biomarker assays can detect bladder
      cancer in a timely manner such that the patient can expect improvements in
      overall survival and quality of life.

PMID- 24920643
TI  - Sciatic nerve injection injury.
AB  - Nerve injury is a common complication following intramuscular injection and the
      sciatic nerve is the most frequently affected nerve, especially in children, the
      elderly and underweight patients. The neurological presentation may range from
      minor transient pain to severe sensory disturbance and motor loss with poor
      recovery. Management of nerve injection injury includes drug treatment of pain,
      physiotherapy, use of assistive devices and surgical exploration. Early
      recognition of nerve injection injury and appropriate management are crucial in
      order to reduce neurological deficit and to maximize recovery. Sciatic nerve
      injection injury is a preventable event. Total avoidance of intramuscular
      injection is recommended if other administration routes can be used. If the
      injection has to be administered into the gluteal muscle, the ventrogluteal
      region (gluteal triangle) has a more favourable safety profile than the
      dorsogluteal region (the upper outer quadrant of the buttock). 

PMID- 24920642
TI  - Predicted 25(OH)D score and colorectal cancer risk according to vitamin D
      receptor expression.
AB  - BACKGROUND: Despite accumulating evidence for the preventive effect of vitamin D
      on colorectal carcinogenesis, its precise mechanisms remain unclear. We
      hypothesized that vitamin D was associated with a lower risk of colorectal cancer
      with high-level vitamin D receptor (VDR) expression, but not with risk of tumor
      with low-level VDR expression. METHODS: Among 140,418 participants followed from
      1986 through 2008 in the Nurses' Health Study and the Health Professionals'
      Follow-up Study, we identified 1,059 incident colorectal cancer cases with tumor
      molecular data. The predicted 25-hydroxyvitamin D [25(OH)D] score was developed
      using the known determinants of plasma 25(OH)D. We estimated the HR for cancer
      subtypes using the duplication method Cox proportional hazards model. RESULTS: A
      higher predicted 25(OH)D score was associated with a lower risk of colorectal
      cancer irrespective of VDR expression level (P(heterogeneity) for subtypes =
      0.75). Multivariate HRs (95% confidence intervals) comparing the highest with the
      lowest quintile of predicted 25(OH)D scores were 0.48 (0.30-0.78) for VDR
      negative tumor and 0.56 (0.42-0.75) for VDR-positive tumor. Similarly, the
      significant inverse associations of the predicted 25(OH)D score with colorectal
      cancer risk did not significantly differ by KRAS, BRAF, or PIK3CA status
      (P(heterogeneity) for subtypes >= 0.22). CONCLUSIONS: A higher predicted vitamin
      D score was significantly associated with a lower colorectal cancer risk,
      regardless of VDR status and other molecular features examined. IMPACT: The
      preventive effect of vitamin D on colorectal carcinogenesis may not totally
      depend on tumor factors. Host factors (such as local and systemic immunity) may
      need to be considered.

PMID- 24920645
TI  - Commentary: Potential implications of non-specific effects of childhood vaccines.

PMID- 24920644
TI  - The non-specific effects of vaccines and other childhood interventions: the
      contribution of INDEPTH Health and Demographic Surveillance Systems.
AB  - Most childhood interventions (vaccines, micronutrients) in low-income countries
      are justified by their assumed effect on child survival. However, usually the
      interventions have only been studied with respect to their disease/deficiency
      specific effects and not for their overall effects on morbidity and mortality. In
      many situations, the population-based effects have been very different from the
      anticipated effects; for example, the measles-preventive high-titre measles
      vaccine was associated with 2-fold increased female mortality; BCG reduces
      neonatal mortality although children do not die of tuberculosis in the neonatal
      period; vitamin A may be associated with increased or reduced child mortality in
      different situations; effects of interventions may differ for boys and girls. The
      reasons for these and other contrasts between expectations and observations are
      likely to be that the immune system learns more than specific prevention from an
      intervention; such training may enhance or reduce susceptibility to unrelated
      infections. INDEPTH member centres have been in an ideal position to document
      such additional non-specific effects of interventions because they follow the
      total population long term. It is proposed that more INDEPTH member centres
      extend their routine data collection platform to better measure the use and
      effects of childhood interventions. In a longer perspective, INDEPTH may come to
      play a stronger role in defining health research issues of relevance to low
      income countries. 

PMID- 24920646
TI  - Commentary: Alcohol use disorder: as usual, prevention is better than cure.

PMID- 24920647
TI  - Intervertebral disc characterization by shear wave elastography: An in vitro
      preliminary study.
AB  - Patient-specific numerical simulation of the spine is a useful tool both in
      clinic and research. While geometrical personalization of the spine is no more an
      issue, thanks to recent technological advances, non-invasive personalization of
      soft tissue's mechanical properties remains a challenge. Ultrasound elastography
      is a relatively recent measurement technique allowing the evaluation of soft
      tissue's elastic modulus through the measurement of shear wave speed. The aim of
      this study was to determine the feasibility of elastographic measurements in
      intervertebral disc. An in vitro approach was chosen to test the hypothesis that
      shear wave speed can be used to evaluate intervertebral disc mechanical
      properties and to assess measurement repeatability. In total, 11 oxtail
      intervertebral discs were tested in compression to determine their stiffness and
      apparent elastic modulus at rest and at 400 N. Elastographic measurements were
      performed in these two conditions and compared to these mechanical parameters.
      The protocol was repeated six times to determine elastographic measurement
      repeatability. Average shear wave speed over all samples was 5.3 +/- 1.0 m/s,
      with a repeatability of 7% at rest and 4.6% at 400 N; stiffness and apparent
      elastic modulus were 266.3 +/- 70.5 N/mm and 5.4 +/- 1.1 MPa at rest,
      respectively, while at 400 N they were 781.0 +/- 153.8 N/mm and 13.2 +/- 2.4 MPa,
      respectively. Correlations were found between elastographic measurements and
      intervertebral disc mechanical properties; these preliminary results are
      promising for further in vivo application.

PMID- 24920648
TI  - User-generated quality standards for youth mental health in primary care: a
      participatory research design using mixed methods.
AB  - OBJECTIVES: To develop user-generated quality standards for young people with
      mental health problems in primary care using a participatory research model.
      METHODS: 50 young people aged 16-25 from community settings and primary care
      participated in focus groups and interviews about their views and experiences of
      seeking help for mental health problems in primary care, cofacilitated by young
      service users and repeated to ensure respondent validation. A second group of
      young people also aged 16-25 who had sought help for any mental health problem
      from primary care or secondary care within the last 5 years were trained as focus
      groups cofacilitators (n=12) developed the quality standards from the qualitative
      data and participated in four nominal groups (n=28). RESULTS: 46 quality
      standards were developed and ranked by young service users. Agreement was defined
      as 100% of scores within a two-point region. Group consensus existed for 16
      quality standards representing the following aspects of primary care: better
      advertising and information (three); improved competence through mental health
      training and skill mix within the practice (two); alternatives to medication
      (three); improved referral protocol (three); and specific questions and
      reassurances (five). Alternatives to medication and specific questions and
      reassurances are aspects of quality which have not been previously reported.
      CONCLUSIONS: We have demonstrated the feasibility of using participatory research
      methods in order to develop user-generated quality standards. The development of
      patient-generated quality standards may offer a more formal method of
      incorporating the views of service users into quality improvement initiatives.
      This method can be adapted for generating quality standards applicable to other
      patient groups.

PMID- 24920649
TI  - Optimal placement and angulation of a dorsal motion control mechanism to resist
      heel rise in an orthosis.
AB  - BACKGROUND: No studies have determined the optimal location and angular
      orientation for orthotic dorsal control mechanisms (e.g. dorsal foot strap) for
      use in lower limb orthoses to resist foot motion for maximum user function and
      comfort. OBJECTIVES: To determine the optimal dorsal location and angular
      orientation of an orthotic control mechanism to resist foot movements associated
      with heel rise. STUDY DESIGN: An in vitro cadaveric study quantified the dorsal
      force required to resist foot motion. METHODS: The study simulated heel rise and
      quantified the force of a dorsal control mechanism in nine test conditions
      comprising three angles (75 degrees , 90 degrees , and 105 degrees ) and three
      longitudinal axis positions at 2.0 cm increments. RESULTS: The test condition
      representing the longest lever arm (proximal location) applied at an obtuse angle
      (105 degrees ) required the least force (55.6 N) to constrain foot motion,
      whereas the shortest lever arm (distal location) at the acute angle (75 degrees )
      required the greatest force (90.4 N) to constrain foot motion. CONCLUSION: To
      resist foot motion relative to the orthosis, clinicians should aim for the most
      proximal placement (longest lever arm) at an obtuse angle (105 degrees ) with the
      intention that the resultant controlling force be perpendicular to the bony
      structure. CLINICAL RELEVANCE: A dorsal foot control strap applies a critical
      orthotic corrective force, as part of a force couple to restrict motion of the
      foot and shank in lower limb orthoses. Foundational orthotic principles that
      stipulate optimal clinical placement and angular orientation are necessary to
      ensure maximum function and comfort to users.

PMID- 24920650
TI  - Factor structure, evolution, and predictive power of emotional competencies on
      physical and emotional health in the elderly.
AB  - OBJECTIVE: Emotional competence (EC) has been found to be an important predictor
      of individuals' health. While it is well known that EC predicts important
      outcomes in young adults, its importance is less clear in the elderly. We aimed
      to address this gap: Is the structure of EC the same in older as in younger
      adults? How do EC evolve between 50 and 80 years old? Does the predictive power
      of EC, regarding physical and emotional adjustment, increase or decrease with
      age? METHOD: A total of 6,688 participants filled subjective health and EC
      questionnaires. We gathered their medication consumption over the last 11 years,
      from the database of health insurance. RESULTS: While the structure of ECs
      remains stable in older adults, it generally declines as people get older, except
      for emotion regulation, which improves with age. Results also show that EC
      predicts both physical and emotional health. DISCUSSION: These results suggest
      that the development of specific interventions to improve EC may be useful for
      the elderly.

PMID- 24920651
TI  - Nucleotide sequences of 16 transmissible plasmids identified in nine multidrug
      resistant Escherichia coli isolates expressing an ESBL phenotype isolated from
      food-producing animals and healthy humans.
AB  - OBJECTIVES: Nine extended-spectrum beta-lactamase (ESBL)-producing Escherichia
      coli isolated from healthy humans and food-producing animals were found to
      transfer their cefotaxime resistance marker at high frequency in laboratory
      conjugation experiments. The objective of this study was to completely
      characterize 16 transmissible plasmids that were detected in these bacterial
      isolates. METHODS: The nucleotide sequences of all 16 plasmids were determined
      from transconjugants using next-generation sequencing technology. Open reading
      frames were assigned using Rapid Annotation using Subsystem Technology and
      analysed by BLASTn and BLASTp. The standard method was used for plasmid
      multilocus sequence typing (pMLST) analysis. Plasmid structures were subsequently
      confirmed by PCR amplification of selected regions. RESULTS: The complete
      circularized nucleotide sequence of 14 plasmids was determined, along with that
      of a further two plasmids that could not be confirmed as closed. These ranged in
      size from 1.8 to 166.6 kb. Incompatibility groups and pMLSTs identified included
      IncI1/ST3, IncI1/ST36, IncN/ST1, IncF and IncB/O, and those of the same Inc types
      presented a similar backbone structure despite being isolated from different
      sources. Eight plasmids contained bla(CTX-M-1) genes that were associated with
      either ISEcp1 or IS26 insertion sequence elements. Six plasmids isolated from
      humans and chickens were identical or closely related to the IncI1 reference
      plasmid, R64. CONCLUSIONS: These data, based on comparative sequence analysis,
      highlight the successful spread of blaESBL-harbouring plasmids of different Inc
      types among isolates of human and food-producing animal origin and provide
      further evidence for potential dissemination routes.

PMID- 24920652
TI  - Clinical cure rates in subjects treated with azithromycin for community-acquired
      respiratory tract infections caused by azithromycin-susceptible or azithromycin
      resistant Streptococcus pneumoniae: analysis of Phase 3 clinical trial data.
AB  - BACKGROUND: Community-acquired respiratory tract infections (CARTI) are commonly
      caused by Streptococcus pneumoniae (SPN) and empirically treated with
      azithromycin. This study assessed clinical cure rates in azithromycin-treated
      subjects with CARTI caused by azithromycin-susceptible (Azi-S) or azithromycin
      resistant (Azi-R) SPN. METHODS: 1127 subjects with CARTI (402 acute otitis media,
      309 community-acquired pneumonia, 255 acute bacterial exacerbations of chronic
      bronchitis and 161 acute bacterial sinusitis) in 13 Phase 3 clinical trials (1993
      2007) had a confirmed pathogen, received azithromycin and were assessed for
      clinical cure/failure. 34.4% of subjects (388/1127) had a positive culture for
      SPN; 33.4% (376/1127) had Azi-S or Azi-R SPN. RESULTS: 28.9% (112/388) of
      subjects with SPN had Azi-R SPN: 35.7% (40/112) were low-level Azi-R SPN (LLAR;
      MIC 2-8 mg/L), while 64.3% (72/112) were high-level Azi-R SPN (HLAR; MIC >=16
      mg/L). Among Azi-S and Azi-R SPN CARTI subjects, clinical cure rates were: 86.2%
      (324/376) overall; 89.4% (236/264) for subjects with Azi-S SPN; 78.6% (88/112)
      for subjects with Azi-R SPN (P = 0.003, versus Azi-S); 77.5% (31/40) for subjects
      with LLAR SPN (P < 0.001); and 79.2% (57/72) for subjects with HLAR SPN (P =
      0.122). CONCLUSIONS: Clinical cure rates in CARTI subjects treated with
      azithromycin were higher for Azi-S SPN (89.4%) versus Azi-R SPN (78.6%; P =
      0.003). However, cure rates were not different for subjects infected with LLAR
      SPN versus HLAR-SPN. At the observed prevalence of Azi-R SPN of 28.9%, an
      additional 3.1 clinical failures would be predicted, as a consequence of
      azithromycin resistance (LLAR and HLAR), per 100 subjects treated empirically
      with azithromycin.

PMID- 24920653
TI  - An optimized method for corticosterone analysis in mouse plasma by ultra
      performance liquid chromatography-full-scan high-resolution accurate mass
      spectrometry.
AB  - A simple method based on liquid chromatography-full-scan high-resolution accurate
      mass spectrometry (LC-HRMS) using a quadrupole time-of-flight (TOF) mass
      spectrometry was developed and optimized for corticosterone quantification in
      mouse plasma. Mouse plasma (100 MUL) was extracted with methyl tert-butyl ether
      using prednisone as internal standard. Separation was performed on a short C18
      column using a methanol-water gradient. Full-scan data were acquired in the TOF
      only mode, and extracted ion chromatograms were generated post-acquisition with
      the extract masses of the analytes. Enhanced sensitivity and reproducibility were
      acquired with optimized mass parameters. The calibration range was 8.24-412
      ng/mL, and the limit of quantitation was 5.088 g/mL. Accuracy was between -5.9
      and 8.6%. The precision of between-run (interday) and within-run (intraday) was
      within 5.6 and 6.9%, respectively. The LC-HRMS method was applied for plasma
      samples analysis from the stressed mice with and without ginseng treatment for
      the stress state estimation. 

PMID- 24920654
TI  - Simultaneous determination of five constituents in Qinpijiegu capsule by high
      performance liquid chromatography coupled with tandem mass spectrometry.
AB  - A rapid high-performance liquid chromatography coupled with tandem mass
      spectrometry method was developed for the simultaneous determination of five
      constituents in Qinpijiegu capsule (QJC), a classical Tibetan prescription. The
      separation of five compounds such as aesculin, aesculetin, fraxin, peimine and
      peiminine was performed on a Purospher STAR LP RP-C18 (250 * 4.6 mm, 5 MUm)
      column with linear gradient elution of acetonitrile-0.30/00 formic acid water in
      13 min. Detection was carried out by multiple reaction monitoring mode using
      electrospray ionization in the positive and negative ion switching mode. The
      sample was prepared with ultrasound extraction with methanol, which could obtain
      higher extraction efficiency and shorter extraction time comparing to reflux
      extraction with alkalized chloroform-methanol. The proposed method was applied to
      analyze three batches of samples with acceptable linearity (r(2) > 0.9977),
      precision [relative standard deviation (RSD) < 7.40%], repeatability (RSD <
      2.49%), stability [relative error (RE) < 9.15%] and recovery (RSD < 10.76%). This
      is the first development of a multicomponent quantitation method for the quality
      control of QJC. Furthermore, the new established method was proven to be highly
      sensitive and effective in evaluating the quality of QJC. 

PMID- 24920655
TI  - Detection and chemical profiling of Ling-Gui-Zhu-Gan decoction by ultra
      performance liquid chromatography-hybrid linear ion trap-Orbitrap mass
      spectrometry.
AB  - Ling-Gui-Zhu-Gan decoction (LGZGD), a well-known traditional Chinese medicine
      (TCM) formula, has been extensively used for the treatment of cardiovascular
      disease in clinic. However, the chemical constituents in LGZGD had not been
      investigated so far. In this study, an ultra performance liquid chromatography
      hybrid electrospray ionization linear ion trap-Orbitrap mass spectrometry (UPLC
      LTQ-Oribitrap-MS/MS) method was established for rapid separation and structural
      identification of the constituents in LGZGD. Separation was performed on an
      ACQUITY(TM) UPLC BEH C18 column (50 * 2.1 mm, 1.7 MUm) by gradient elution mode,
      using acetonitrile-water containing 0.1% formic acid as mobile phase at the flow
      rate of 0.2 mL/min. Accurate mass measurement for molecular ions and
      characteristic fragment ions could represent identification criteria for these
      compounds. As a result, 95 compounds including triterpene acids, triterpene
      saponins, flavonoids, coumarins, coumestans, benzofurans, phenylpropanoids and
      sesquiterpenoid lactones were detected, and 90 of them were tentatively
      identified. All compounds were further assigned in the individual raw material.
      In conclusion, the UPLC-LTQ-Orbitrap-MS/MS is a highly efficient technique to
      separate and identify constituents in complex matrices of TCMs. These results
      obtained in this research will provide a basis for quality control and further in
      vivo study of LGZGD. 

PMID- 24920656
TI  - Multivariate curve resolution-assisted determination of pseudoephedrine and
      methamphetamine by HPLC-DAD in water samples.
AB  - In the present study, a simple strategy based on solid-phase extraction (SPE)
      with a cation exchange sorbent (Finisterre SCX) followed by fast high-performance
      liquid chromatography (HPLC) with diode array detection coupled with chemometrics
      tools has been proposed for the determination of methamphetamine and
      pseudoephedrine in ground water and river water. At first, the HPLC and SPE
      conditions were optimized and the analytical performance of the method was
      determined. In the case of ground water, determination of analytes was
      successfully performed through univariate calibration curves. For river water
      sample, multivariate curve resolution and alternating least squares was
      implemented and the second-order advantage was achieved in samples containing
      uncalibrated interferences and uncorrected background signals. The calibration
      curves showed good linearity (r(2) > 0.994).The limits of detection for
      pseudoephedrine and methamphetamine were 0.06 and 0.08 MUg/L and the average
      recovery values were 104.7 and 102.3% in river water, respectively. 

PMID- 24920657
TI  - From knowledge to policy: lessons from Africa.

PMID- 24920658
TI  - RNAi therapies: drugging the undruggable.
AB  - RNA interference (RNAi) therapy is a rapidly emerging platform for personalized
      cancer treatment. Recent advances in small interfering RNA delivery and target
      selection provide unprecedented opportunities for clinical translation. Here, we
      discuss these advances and present strategies for making RNAi-based therapy a
      viable part of cancer management. 

PMID- 24920659
TI  - Macrophage models of Gaucher disease for evaluating disease pathogenesis and
      candidate drugs.
AB  - Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that
      manifests with storage of glycolipids in lysosomes, particularly in macrophages.
      Available cell lines modeling Gaucher disease do not demonstrate lysosomal
      storage of glycolipids; therefore, we set out to develop two macrophage models of
      Gaucher disease that exhibit appropriate substrate accumulation. We used these
      cellular models both to investigate altered macrophage biology in Gaucher disease
      and to evaluate candidate drugs for its treatment. We generated and characterized
      monocyte-derived macrophages from 20 patients carrying different Gaucher disease
      mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived
      macrophages from five fibroblast lines taken from patients with type 1 or type 2
      Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed
      reduced glucocerebrosidase activity and increased storage of glucocerebroside and
      glucosylsphingosine in lysosomes. These macrophages showed efficient phagocytosis
      of bacteria but reduced production of intracellular reactive oxygen species and
      impaired chemotaxis. The disease phenotype was reversed with a noninhibitory
      small-molecule chaperone drug that enhanced glucocerebrosidase activity in the
      macrophages, reduced glycolipid storage, and normalized chemotaxis and production
      of reactive oxygen species. Macrophages differentiated from patient monocytes or
      patient-derived iPSCs provide cellular models that can be used to investigate
      disease pathogenesis and facilitate drug development. 

PMID- 24920660
TI  - Identification of a new modulator of the intercalated disc in a zebrafish model
      of arrhythmogenic cardiomyopathy.
AB  - Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac
      arrhythmias. To elucidate the underlying mechanisms and discover potential
      chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte
      specific expression of the human 2057del2 mutation in the gene encoding
      plakoglobin. A high-throughput screen identified SB216763 as a suppressor of the
      disease phenotype. Early SB216763 therapy prevented heart failure and reduced
      mortality in the fish model. Zebrafish ventricular myocytes that expressed
      2057del2 plakoglobin exhibited 70 to 80% reductions in I(Na) and I(K1) current
      densities, which were normalized by SB216763. Neonatal rat ventricular myocytes
      that expressed 2057del2 plakoglobin recapitulated pathobiological features seen
      in patients with ACM, all of which were reversed or prevented by SB216763. The
      reverse remodeling observed with SB216763 involved marked subcellular
      redistribution of plakoglobin, connexin 43, and Nav1.5, but without changes in
      their total cellular content, implicating a defect in protein trafficking to
      intercalated discs. In further support of this mechanism, we observed SB216763
      reversible, abnormal subcellular distribution of SAP97 (a protein known to
      mediate forward trafficking of Nav1.5 and Kir2.1) in rat cardiac myocytes
      expressing 2057del2 plakoglobin and in cardiac myocytes derived from induced
      pluripotent stem cells from two ACM probands with plakophilin-2 mutations. These
      observations pinpoint aberrant trafficking of intercalated disc proteins as a
      central mechanism in ACM myocyte injury and electrical abnormalities.

PMID- 24920661
TI  - Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy.
AB  - Many solid tumors contain an overabundance of phospholipid ethers relative to
      normal cells. Capitalizing on this difference, we created cancer-targeted
      alkylphosphocholine (APC) analogs through structure-activity analyses. Depending
      on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either
      a positron emission tomography (PET) imaging ((124)I) or molecular
      radiotherapeutic ((131)I) agent. CLR1404 analogs displayed prolonged tumor
      selective retention in 55 in vivo rodent and human cancer and cancer stem cell
      models. (131)I-CLR1404 also displayed efficacy (tumor growth suppression and
      survival extension) in a wide range of human tumor xenograft models. Human PET/CT
      (computed tomography) and SPECT (single-photon emission computed tomography)/CT
      imaging in advanced-cancer patients with (124)I-CLR1404 or (131)I-CLR1404,
      respectively, demonstrated selective uptake and prolonged retention in both
      primary and metastatic malignant tumors. Combined application of these chemically
      identical APC-based radioisosteres will enable personalized dual modality cancer
      therapy of using molecular (124)I-CLR1404 tumor imaging for planning (131)I
      CLR1404 therapy. 

PMID- 24920663
TI  - PARK7 protein translocating into spermatozoa mitochondria in Chinese
      asthenozoospermia.
AB  - PARK7 (DJ1) is a multifunctional oxidative stress response protein that protects
      cells against reactive oxygen species (ROS) and mitochondrial damage. PARK7
      defects are known to cause various physiological dysfunctions, including
      infertility. Asthenozoospermia (AS), i.e. low-motile spermatozoa in the
      ejaculate, is a common cause of human male infertility. In this study, we found
      that downregulation of PARK7 resulted in increased levels of lipid peroxide and
      ROS, decreased mitochondrial membrane potential, and reduced mitochondrial
      complex I enzyme activity in the spermatozoa from AS patients. Furthermore, it
      was observed that PARK7 was translocated into the mitochondria of damaged
      spermatozoa in AS. Finally, we examined the oxidative state of PARK7 and the
      results demonstrated the enhancement of oxidation, expressed by increased
      sulfonic acid residues, the highest form of oxidation, as the sperm motility
      decreased. Taken together, these results revealed that PARK7 deficiency may
      increase the oxidative stress damage to spermatozoa. Our present findings open
      new avenues of therapeutic intervention targeting PARK7 for the treatment of AS. 

PMID- 24920664
TI  - Activation of innate immune system in response to lipopolysaccharide in chicken
      Sertoli cells.
AB  - Sertoli cells (SCs) play an important physiological role in the testis, as they
      support, nourish, and protect the germ cells. As protection of the developing
      spermatozoa is an emerging aspect of reproductive physiology, this study examined
      the expression pattern of innate immune-related genes, including avian beta
      defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated
      the time course of an inflammatory response in rooster SCs triggered by exposure
      to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6
      week-old chicken, cultured in vitro, and stimulated with 1 MUg/ml LPS at
      different time courses (0, 6, 12, 24, and 48  h). Data on expression analysis
      revealed that all ten members of the chicken TLR family, nine members of the AvBD
      family, as well as eight cytokine genes were expressed in SCs. Quantitative real
      time PCR analysis revealed that LPS treatment resulted in significant induction
      of the expression levels of six TLRs, six AvBDs, and four cytokine genes, while
      two cytokine genes were downregulated and two other genes were unchanged. The
      increasing interleukin 1beta (IL1beta) production was confirmed in the
      conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS
      treatment. In conclusion, these findings provide evidence that SCs express innate
      immune-related genes and respond directly to bacterial ligands. These genes
      represent an important component of the immune system, which could be integrated
      into semen, and present a distinctive constituent of the protective repertoire of
      the testis against ascending infections.

PMID- 24920662
TI  - Chitinase 3-like 1 suppresses injury and promotes fibroproliferative responses in
      Mammalian lung fibrosis.
AB  - Epithelial injury, alternative macrophage accumulation, and fibroproliferation
      coexist in the lungs of patients with idiopathic pulmonary fibrosis (IPF).
      Chitinase 3-like 1 (CHI3L1) is a prototypic chitinase-like protein that has been
      retained over species and evolutionary time. However, the regulation of CHI3L1 in
      IPF and its ability to regulate injury and/or fibroproliferative repair have not
      been fully defined. We demonstrated that CHI3L1 levels were elevated in patients
      with IPF. High levels of CHI3L1 are associated with progression--as defined by
      lung transplantation or death--and with scavenger receptor-expressing circulating
      monocytes in an ambulatory IPF population. In preterminal acute exacerbations of
      IPF, CHI3L1 levels were reduced and associated with increased levels of
      apoptosis. We also demonstrated that in bleomycin-treated mice, CHI3L1 expression
      was acutely and transiently decreased during the injury phase and returned toward
      and eventually exceeded baseline levels during the fibrotic phase. In this model,
      CHI3L1 played a protective role in injury by ameliorating inflammation and cell
      death, and a profibrotic role in the repair phase by augmenting alternative
      macrophage activation, fibroblast proliferation, and matrix deposition. Using
      three-dimensional culture system of a human fibroblast cell line, we found that
      CHI3L1 is sufficient to induce low grade myofibroblast transformation. In
      combination, these studies demonstrate that CHI3L1 is stimulated in IPF, where it
      represents an attempt to diminish injury and induce repair. They also demonstrate
      that high levels of CHI3L1 are associated with disease progression in ambulatory
      patients and that a failure of the CHI3L1 antiapoptotic response might contribute
      to preterminal disease exacerbations.

PMID- 24920665
TI  - Characterization of microRNAs differentially expressed during bovine follicle
      development.
AB  - Several different miRNAs have been proposed to regulate ovarian follicle
      function; however, very limited information exists on the spatiotemporal patterns
      of miRNA expression during follicle development. The objective of this study was
      to identify, using microarray, miRNA profiles associated with growth and
      regression of dominant-size follicles in the bovine monovular ovary and to
      characterize their spatiotemporal distribution during development. The follicles
      were collected from abattoir ovaries and classified as small (4-8  mm) or large
      (12-17  mm); the latter were further classified as healthy or atretic based on
      estradiol and CYP19A1 levels. Six pools of small follicles and individual large
      healthy (n=6) and large atretic (n=5) follicles were analyzed using Exiqon's
      miRCURY LNA microRNA Array 6th gen, followed by qPCR validation. A total of 17
      and 57 sequences were differentially expressed (greater than or equal to twofold;
      P<0.05) between large healthy and each of small and large atretic follicles
      respectively. Bovine miRNAs confirmed to be upregulated in large healthy
      follicles relative to small follicles (bta-miR-144, bta-miR-202, bta-miR-451, bta
      miR-652, and bta-miR-873) were further characterized. Three of these miRNAs (bta
      miR-144, bta-miR-202, and bta-miR-873) were also downregulated in large atretic
      follicles relative to large healthy follicles. Within the follicle, these miRNAs
      were predominantly expressed in mural granulosa cells. Further, body-wide
      screening revealed that bta-miR-202, but not other miRNAs, was expressed
      exclusively in the gonads. Finally, a total of 1359 predicted targets of the five
      miRNAs enriched in large healthy follicles were identified, which mapped to
      signaling pathways involved in follicular cell proliferation, steroidogenesis,
      prevention of premature luteinization, and oocyte maturation.

PMID- 24920666
TI  - Cross-sectional study of genital carcinogenic HPV infections in Paramaribo,
      Suriname: prevalence and determinants in an ethnically diverse population of
      women in a pre-vaccination era.
AB  - OBJECTIVE: Cervical cancer is caused by carcinogenic human papillomavirus (HPV)
      infections. Prior to the introduction of HPV vaccination in Suriname, we
      performed a cross-sectional study to estimate the prevalence of and determinants
      for genital carcinogenic HPV infections. METHODS: Women were recruited at a
      family planning (FP) clinic and a sexually transmitted infections (STI) clinic.
      Vaginal swabs were used for HPV genotyping by the SPF10 PCR-DEIA-LiPA25 system.
      Logistic regression was used to identify determinants for carcinogenic HPV
      infection. RESULTS: The prevalence of any HPV was 54.2% and of carcinogenic HPV
      was 27.9% among 813 women attending the FP clinic. Among the 188 women attending
      the STI clinic, the prevalence of any HPV (76.1%) and of carcinogenic HPV (40.4%)
      was significantly higher. HPV52 was the most prevalent genotype in both clinics.
      The prevalence of HPV16 and/or 18 was 6.4% in the FP clinic and 12.2% in the STI
      clinic. The following determinants were independently associated with
      carcinogenic HPV infection among women visiting the FP clinic: >=2 recent
      partners (OR 1.53; 95% CI 1.13 to 2.06), Chlamydia trachomatis co-infection (OR
      1.89; 95% CI 1.32 to 2.70), disassortative ethnic sexual mixing (OR 1.50; 95% CI
      1.13 to 1.99) and ethnic group (OR 1.90; 95% CI 1.27 to 2.85 for Creole and OR
      1.67; 95% CI 1.06 to 2.62 for mixed ethnicity, both compared with Hindustani). No
      independent determinants were found among women visiting the STI clinic.
      CONCLUSIONS: Carcinogenic HPV is highly prevalent among women in Suriname, and
      not equally distributed among ethnic groups. These data provide a baseline to
      assess possible shifts in the prevalence of HPV genotypes following vaccination.

PMID- 24920667
TI  - Targeted leptin receptor blockade: role of ventral tegmental area and nucleus of
      the solitary tract leptin receptors in body weight homeostasis.
AB  - The present investigation examined whether leptin stimulation of ventral
      tegmental area (VTA) or nucleus of the solitary tract (NTS) has a role in body
      weight homeostasis independent of the medial basal hypothalamus (MBH). To this
      end, recombinant adeno-associated viral techniques were employed to target leptin
      overexpression or overexpression of a dominant negative leptin mutant (leptin
      antagonist). Leptin antagonist overexpression in MBH or VTA increased food intake
      and body weight to similar extents over 14 days in rats. Simultaneous
      overexpression of leptin in VTA with antagonist in MBH resulted in food intake
      and body weight gain that were less than with control treatment but greater than
      with leptin alone in VTA. Notably, leptin overexpression in VTA increased P-STAT3
      in MBH along with VTA, and leptin antagonist overexpression in the VTA partially
      attenuated P-STAT3 levels in MBH. Interestingly, leptin antagonist overexpression
      elevated body weight gain, but leptin overexpression in the NTS failed to
      modulate either food intake or body weight despite increased P-STAT3. These data
      suggest that leptin function in the VTA participates in the chronic regulation of
      food consumption and body weight in response to stimulation or blockade of VTA
      leptin receptors. Moreover, one component of VTA-leptin action appears to be
      independent of the MBH, and another component appears to be related to leptin
      receptor-mediated P-STAT3 activation in the MBH. Finally, leptin receptors in the
      NTS are necessary for normal energy homeostasis, but mostly they appear to have a
      permissive role. Direct leptin activation of NTS slightly increases UCP1 levels,
      but has little effect on food consumption or body weight. 

PMID- 24920668
TI  - Unstable reaction intermediates and hysteresis during the catalytic cycle of 5
      aminolevulinate synthase: implications from using pseudo and alternate substrates
      and a promiscuous enzyme variant.
AB  - 5-Aminolevulinate (ALA), an essential metabolite in all heme-synthesizing
      organisms, results from the pyridoxal 5'-phosphate (PLP)-dependent enzymatic
      condensation of glycine with succinyl-CoA in non-plant eukaryotes and alpha
      proteobacteria. The predicted chemical mechanism of this ALA synthase (ALAS)
      catalyzed reaction includes a short-lived glycine quinonoid intermediate and an
      unstable 2-amino-3-ketoadipate intermediate. Using liquid chromatography coupled
      with tandem mass spectrometry to analyze the products from the reaction of murine
      erythroid ALAS (mALAS2) with O-methylglycine and succinyl-CoA, we directly
      identified the chemical nature of the inherently unstable 2-amino-3-ketoadipate
      intermediate, which predicates the glycine quinonoid species as its precursor.
      With stopped-flow absorption spectroscopy, we detected and confirmed the
      formation of the quinonoid intermediate upon reacting glycine with ALAS.
      Significantly, in the absence of the succinyl-CoA substrate, the external
      aldimine predominates over the glycine quinonoid intermediate. When instead of
      glycine, L-serine was reacted with ALAS, a lag phase was observed in the progress
      curve for the L-serine external aldimine formation, indicating a hysteretic
      behavior in ALAS. Hysteresis was not detected in the T148A-catalyzed L-serine
      external aldimine formation. These results with T148A, a mALAS2 variant, which,
      in contrast to wild-type mALAS2, is active with L-serine, suggest that active
      site Thr-148 modulates ALAS strict amino acid substrate specificity. The rate of
      ALA release is also controlled by a hysteretic kinetic mechanism (observed as a
      lag in the ALA external aldimine formation progress curve), consistent with
      conformational changes governing the dissociation of ALA from ALAS.

PMID- 24920669
TI  - Glutathione adducts on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase Cys-674
      regulate endothelial cell calcium stores and angiogenic function as well as
      promote ischemic blood flow recovery.
AB  - The sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) is key to Ca(2+)
      homeostasis and is redox-regulated by reversible glutathione (GSH) adducts on the
      cysteine (C) 674 thiol that stimulate Ca(2+) uptake activity and endothelial cell
      angiogenic responses in vitro. We found that mouse hind limb muscle ischemia
      induced S-glutathione adducts on SERCA in both whole muscle tissue and
      endothelial cells. To determine the role of S-glutathiolation, we used a SERCA 2
      C674S heterozygote knock-in (SKI) mouse lacking half the key thiol. Following
      hind limb ischemia, SKI animals had decreased SERCA S-glutathione adducts and
      impaired blood flow recovery. We studied SKI microvascular endothelial cells in
      which total SERCA 2 expression was unchanged. Cultured SKI microvascular
      endothelial cells showed impaired migration and network formation compared with
      wild type (WT). Ca(2+) studies showed decreased nitric oxide (.NO)-induced
      (45)Ca(2+) uptake into the endoplasmic reticulum (ER) of SKI cells, while Fura-2
      studies revealed lower Ca(2+) stores and decreased vascular endothelial growth
      factor (VEGF)- and .NO-induced Ca(2+) influx. Adenoviral overexpression of
      calreticulin, an ER Ca(2+) binding protein, increased ionomycin-releasable
      stores, VEGF-induced Ca(2+) influx and endothelial cell migration. Taken
      together, these data indicate that the redox-sensitive Cys-674 thiol on SERCA 2
      is required for normal endothelial cell Ca(2+) homeostasis and ischemia-induced
      angiogenic responses, revealing a novel redox control of angiogenesis via Ca(2+)
      stores. 

PMID- 24920670
TI  - RNA granule assembly and disassembly modulated by nuclear factor associated with
      double-stranded RNA 2 and nuclear factor 45.
AB  - RNA granules are large messenger ribonucleoprotein complexes that regulate
      translation and mRNA translocation to control the timing and location of protein
      synthesis. The regulation of RNA granule assembly and disassembly is a structural
      basis of translational control, and its disorder is implicated in degenerative
      disease. Here, we used proteomic analysis to identify proteins associated with
      RNA granule protein 105 (RNG105)/caprin1, an RNA-binding protein in RNA granules.
      Among the identified proteins, we focused on nuclear factor (NF) 45 and its
      binding partner, nuclear factor associated with dsRNA 2 (NFAR2), and we
      demonstrated that NF45 promotes disassembly of RNA granules, whereas NFAR2
      enhances the assembly of RNA granules in cultured cells. The GQSY domain of NFAR2
      was required to associate with messenger ribonucleoprotein complexes containing
      RNG105/caprin1, and it was structurally and functionally related to the low
      complexity sequence domain of the fused in sarcoma protein, which drives the
      assembly of RNA granules. Another domain of NFAR2, the DZF domain, was
      dispensable for association with the RNG105 complex, but it was involved in
      positive and negative regulation of RNA granule assembly by being phosphorylated
      at double-stranded RNA-activated kinase sites and by association with NF45,
      respectively. These results suggest a novel molecular mechanism for the
      modulation of RNA granule assembly and disassembly by NFAR2, NF45, and
      phosphorylation at double-stranded RNA-activated kinase PKR sites.

PMID- 24920671
TI  - Myopathy-causing mutations in an HSP40 chaperone disrupt processing of specific
      client conformers.
AB  - The molecular chaperone network protects against the toxic misfolding and
      aggregation of proteins. Disruption of this network leads to a variety of protein
      conformational disorders. One such example recently discovered is limb-girdle
      muscular dystrophy type 1D (LGMD1D), which is caused by mutation of the HSP40
      chaperone DNAJB6. All LGMD1D-associated mutations localize to the conserved G/F
      domain of DNAJB6, but the function of this domain is largely unknown. Here, we
      exploit the yeast HSP40 Sis1, which has known aggregation-prone client proteins,
      to gain insight into the role of the G/F domain and its significance in LGMD1D
      pathogenesis. Strikingly, we demonstrate that LGMD1D mutations in a Sis1-DNAJB6
      chimera differentially impair the processing of specific conformers of two yeast
      prions, [RNQ+] and [PSI+]. Importantly, these differences do not simply correlate
      to the sensitivity of these prion strains to changes in chaperone levels.
      Additionally, we analyzed the effect of LGMD1D-associated DNAJB6 mutations on TDP
      43, a protein known to form inclusions in LGMD1D. We show that the DNAJB6 G/F
      domain mutants disrupt the processing of nuclear TDP-43 stress granules in
      mammalian cells. These data suggest that the G/F domain mediates chaperone
      substrate interactions in a manner that extends beyond recognition of a
      particular client and to a subset of client conformers. We propose that such
      selective chaperone disruption may lead to the accumulation of toxic aggregate
      conformers and result in the development of LGMD1D and perhaps other protein
      conformational disorders.

PMID- 24920673
TI  - The mechanism of dynein light chain LC8-mediated oligomerization of the Ana2
      centriole duplication factor.
AB  - Centrioles play a key role in nucleating polarized microtubule networks. In
      actively dividing cells, centrioles establish the bipolar mitotic spindle and are
      essential for genomic stability. Drosophila anastral spindle-2 (Ana2) is a
      conserved centriole duplication factor. Although recent work has demonstrated
      that an Ana2-dynein light chain (LC8) centriolar complex is critical for proper
      spindle positioning in neuroblasts, how Ana2 and LC8 interact is yet to be
      established. Here we examine the Ana2-LC8 interaction and map two LC8-binding
      sites within the central region of Ana2, Ana2M (residues 156-251). Ana2 LC8
      binding site 1 contains a signature TQT motif and robustly binds LC8 (KD of 1.1
      MUm), whereas site 2 contains a TQC motif and binds LC8 with lower affinity (KD
      of 13 MUm). Both LC8-binding sites flank a predicted ~34-residue alpha-helix. We
      present two independent atomic structures of LC8 dimers in complex with Ana2 LC8
      binding site 1 and site 2 peptides. The Ana2 peptides form beta-strands that
      extend a central composite LC8 beta-sandwich. LC8 recognizes the signature TQT
      motif in the first LC8 binding site of Ana2, forming extensive van der Waals
      contacts and hydrogen bonding with the peptide, whereas the Ana2 site 2 TQC motif
      forms a uniquely extended beta-strand, not observed in other dynein light chain
      target complexes. Size exclusion chromatography coupled with multiangle static
      light scattering demonstrates that LC8 dimers bind Ana2M sites and induce Ana2
      tetramerization, yielding an Ana2M4-LC88 complex. LC8-mediated Ana2
      oligomerization probably enhances Ana2 avidity for centriole-binding factors and
      may bridge multiple factors as required during spindle positioning and centriole
      biogenesis.

PMID- 24920672
TI  - Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1
      subcomplex.
AB  - The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved
      transcriptional co-regulator that harbors both nucleosome remodeling and histone
      deacetylase activities. It plays a critical role in the early stages of ES cell
      differentiation and the reprogramming of somatic to induced pluripotent stem
      cells. Abnormalities in several NuRD proteins are associated with cancer and
      aging. We have investigated the architecture of NuRD by determining the structure
      of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1
      using the same site that it uses to bind histone H4, showing that assembly into
      NuRD modulates RbAp46/48 interactions with histones. Taken together with other
      results, our data show that the MTA proteins act as scaffolds for NuRD complex
      assembly. We further show that the RbAp48-MTA1 interaction is essential for the
      in vivo integration of RbAp46/48 into the NuRD complex. 

PMID- 24920674
TI  - Molecular mechanisms for the p38-induced cellular senescence in normal human
      fibroblast.
AB  - We previously reported that TAK1, one of the mitogen-activated protein kinase
      kinase kinases (MAP3Ks), represses the transcription of the human telomerase
      reverse transcriptase (hTERT) gene in human cancer cells and induces cellular
      senescence in normal diploid human cells. On the basis of these results, we
      presumed a link between hTERT repression and the induction of cellular
      senescence. In this study, we identified the MAPK p38 as a downstream mediator of
      TAK1, which represses hTERT transcription. Further, we observed that hTERT
      expression was repressed in senescent normal human fibroblast, and was attenuated
      on treatment with SB203580, a p38-specific inhibitor, which suggests that p38
      represses hTERT expression during cellular senescence. Next, we demonstrated that
      repression of hTERT, irrespective of the activation status of p38, is important
      for the induction of cellular senescence, by using hTERT-overexpressing cells and
      hTERT-knockdown cells. Our results suggested that p38 is activated during the
      serial passagings of normal human fibroblast, which results in the repression of
      hTERT transcription and induction of cellular senescence. 

PMID- 24920675
TI  - Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat
      heart.
AB  - As ~80% of diabetic patients die from heart failure, an understanding of diabetic
      cardiomyopathy is crucial. Mitochondria occupy 35-40% of the mammalian
      cardiomyocyte volume and supply 95% of the heart's ATP, and diabetic heart
      mitochondria show impaired structure, arrangement, and function. We predict that
      bioenergetic inefficiencies are present in diabetic heart mitochondria;
      therefore, we explored mitochondrial proton and electron handling by linking
      oxygen flux to steady-state ATP synthesis, reactive oxygen species (ROS)
      production, and mitochondrial membrane potential (DeltaPsi) within rat heart
      tissues. Sprague-Dawley rats were injected with streptozotocin (STZ, 55 mg/kg) to
      induce type 1 diabetes or an equivalent volume of saline (control, n = 12) and
      fed standard rat chow for 8 wk. By coupling high-resolution respirometers with
      purpose-built fluorometers, we followed Magnesium Green (ATP synthesis), Amplex
      UltraRed (ROS production), and safranin-O (DeltaPsi). Relative to control rats,
      the mass-specific respiration of STZ-diabetic hearts was depressed in oxidative
      phosphorylation (OXPHOS) states. Steady-state ATP synthesis capacity was almost
      one-third lower in STZ-diabetic heart, which, relative to oxygen flux, equates to
      an estimated 12% depression in OXPHOS efficiency. However, with anoxic
      transition, STZ-diabetic and control heart tissues showed similar ATP hydrolysis
      capacities through reversal of the F1F0-ATP synthase. STZ-diabetic cardiac
      mitochondria also produced more net ROS relative to oxygen flux (ROS/O) in
      OXPHOS. While DeltaPsi did not differ between groups, the time to develop
      DeltaPsi with the onset of OXPHOS was protracted in STZ-diabetic mitochondria.
      ROS/O is higher in lifelike OXPHOS states, and potential delays in the time to
      develop DeltaPsi may delay ATP synthesis with interbeat fluctuations in ADP
      concentrations. Whereas diabetic cardiac mitochondria produce less ATP in
      normoxia, they consume as much ATP in anoxic infarct-like states.

PMID- 24920676
TI  - Degradation mechanism of a Golgi-retained distal renal tubular acidosis mutant of
      the kidney anion exchanger 1 in renal cells.
AB  - Distal renal tubular acidosis (dRTA) can be caused by mutations in the SLC4A1
      gene encoding the anion exchanger 1 (AE1). Both recessive and dominant mutations
      result in mistrafficking of proteins, preventing them from reaching the
      basolateral membrane of renal epithelial cells, where their function is needed.
      In this study, we show that two dRTA mutants are prematurely degraded. Therefore,
      we investigated the degradation pathway of the kidney AE1 G701D mutant that is
      retained in the Golgi. Little is known about degradation of nonnative membrane
      proteins from the Golgi compartments in mammalian cells. We show that the kidney
      AE1 G701D mutant is polyubiquitylated and degraded by the lysosome and the
      proteosome. This mutant reaches the plasma membrane, where it is endocytosed and
      degraded by the lysosome via a mechanism dependent on the peripheral quality
      control machinery. Furthermore, we show that the function of the mutant is
      rescued at the cell surface upon inhibition of the lysosome and incubation with a
      chemical chaperone. We conclude that modulating the peripheral quality control
      machinery may provide a novel therapeutic option for treatment of patients with
      dRTA due to a Golgi-retained mutant.

PMID- 24920677
TI  - Flow shear stress enhances intracellular Ca2+ signaling in pulmonary artery
      smooth muscle cells from patients with pulmonary arterial hypertension.
AB  - An increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in pulmonary arterial
      smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and
      an important stimulus for pulmonary arterial medial hypertrophy in patients with
      idiopathic pulmonary arterial hypertension (IPAH). Vascular smooth muscle cells
      (SMC) sense the blood flow shear stress through interstitial fluid driven by
      pressure or direct exposure to blood flow in case of endothelial injury.
      Mechanical stimulus can increase [Ca(2+)]cyt. Here we report that flow shear
      stress raised [Ca(2+)]cyt in PASMC, while the shear stress-mediated rise in
      [Ca(2+)]cyt and the protein expression level of TRPM7 and TRPV4 channels were
      significantly greater in IPAH-PASMC than in normal PASMC. Blockade of TRPM7 by 2
      APB or TRPV4 by Ruthenium red inhibited shear stress-induced rise in [Ca(2+)]cyt
      in normal and IPAH-PASMC, while activation of TRPM7 by bradykinin or TRPV4 by
      4alphaPDD induced greater increase in [Ca(2+)]cyt in IPAH-PASMC than in normal
      PASMC. The bradykinin-mediated activation of TRPM7 also led to a greater increase
      in [Mg(2+)]cyt in IPAH-PASMC than in normal PASMC. Knockdown of TRPM7 and TRPV4
      by siRNA significantly attenuated the shear stress-mediated [Ca(2+)]cyt increases
      in normal and IPAH-PASMC. In conclusion, upregulated mechanosensitive channels
      (e.g., TRPM7, TRPV4, TRPC6) contribute to the enhanced [Ca(2+)]cyt increase
      induced by shear stress in PASMC from IPAH patients. Blockade of the
      mechanosensitive cation channels may represent a novel therapeutic approach for
      relieving elevated [Ca(2+)]cyt in PASMC and thereby inhibiting sustained
      pulmonary vasoconstriction and pulmonary vascular remodeling in patients with
      IPAH. 

PMID- 24920678
TI  - Microtubules are required for efficient epithelial tight junction homeostasis and
      restoration.
AB  - Epithelial tight junctions are critical for creating a barrier yet allowing
      paracellular transport. Although it is well established that the actin
      cytoskeleton is critical for preserving the dynamic organization of the tight
      junction and maintaining normal tight junction protein recycling, contributions
      of microtubules to tight junction organization and function remain undefined. The
      aim of this study is to determine the role of microtubules in tight junction
      homeostasis and restoration. Our data demonstrate that occludin traffics on
      microtubules and that microtubule disruption perturbs tight junction structure
      and function. Microtubules are also shown to be required for restoring barrier
      function following Ca(2+) chelation and repletion. These processes are mediated
      by proteins participating in microtubule minus-end-directed trafficking but not
      plus-end-directed trafficking. These studies show that microtubules participate
      in the preservation of epithelial tight junction structure and function and play
      a vital role in tight junction restoration, thus expanding our understanding of
      the regulation of tight junction physiology.

PMID- 24920679
TI  - Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth
      muscle tissues.
AB  - Histone deacetylases (HDACs) are a family of enzymes that mediate nucleosomal
      histone deacetylation and gene expression. Some members of the HDAC family have
      also been implicated in nonhistone protein deacetylation, which modulates cell
      cycle control, differentiation, and cell migration. However, the role of HDACs in
      smooth muscle contraction is largely unknown. Here, HDAC8 was localized both in
      the cytoplasm and the nucleus of mouse and human smooth muscle cells. Knockdown
      of HDAC8 by lentivirus-encoding HDAC8 shRNA inhibited force development in
      response to acetylcholine. Treatment of smooth muscle tissues with HDAC8
      inhibitor XXIV (OSU-HDAC-44) induced relaxation of precontracted smooth muscle
      tissues. In addition, cortactin is an actin-regulatory protein that undergoes
      deacetylation during migration of NIH 3T3 cells. In this study, acetylcholine
      stimulation induced cortactin deacetylation in mouse and human smooth muscle
      tissues, as evidenced by immunoblot analysis using antibody against acetylated
      lysine. Knockdown of HDAC8 by RNAi or treatment with the inhibitor attenuated
      cortactin deacetylation and actin polymerization without affecting myosin
      activation. Furthermore, expression of a charge-neutralizing cortactin mutant
      inhibited contraction and actin dynamics during contractile activation. These
      results suggest a novel mechanism for the regulation of smooth muscle
      contraction. In response to contractile stimulation, HDAC8 may mediate cortactin
      deacetylation, which subsequently promotes actin filament polymerization and
      smooth muscle contraction.

PMID- 24920681
TI  - Application of smoothed continuous labile haemoglobin A1c reference intervals for
      identification of potentially spurious HbA1c results.
AB  - AIMS: We aim to develop smoothed continuous 2.5th and 97.5th percentile values
      for labile glycated haemoglobin A1c to glycated haemoglobin A1c (LHbA1c:HbA1c)
      ratio against HbA1c, and apply them on our patient population for identification
      of potentially spurious HbA1c measurements. METHODS: The LHbA1c and HbA1c were
      measured using Bio-rad Variant II high-performance liquid chromatography system.
      We recorded the LHbA1c and HbA1c values of 1555 patients who had normal
      chromatograms. Using these results, the 2.5th and 97.5th percentile reference
      limits of the LHbA1c:HbA1c ratio were described by LHbA1c:HbA1c=-0.0072*HbA1c
      +0.2925 and LHbA1c:HbA1c=-0.0132*HbA1c +0.5327, respectively. RESULTS: When the
      reference intervals were applied on a separate 1000 patients, 34 and 29 of them
      had abnormally high and low LHbA1c:HbA1c ratios, respectively. Most of the
      observed high ratios were associated concurrently with elevated plasma glucose,
      anaemia, chronic liver and kidney diseases. A suppressed ratio was mostly
      associated with haemoglobin variants. Patients with heterozygous HbE or HbS
      variants tend to have lower LHbA1c:HbA1c ratios while the converse is true for
      heterozygous HbJ. CONCLUSIONS: The continuous LHbA1c:HbA1c ratio may be used to
      detect confounding factors or spurious HbA1c results, but its performance is
      confounded and reduced by the ambient plasma glucose.

PMID- 24920680
TI  - SMAD3 augments FoxO3-induced MuRF-1 promoter activity in a DNA-binding-dependent
      manner.
AB  - Muscle-specific RING finger-1 (MuRF-1), a ubiquitin ligase and key regulator of
      proteasome-dependent protein degradation, is highly expressed during skeletal
      muscle atrophy. The transcription factor forkhead box O3 (FoxO3) induces MuRF-1
      expression, but the direct role of other major atrophy-related transcription
      factors, such as SMAD3, is largely unknown. The goal of this study was to
      determine whether SMAD3 individually regulates, or with FoxO3 coordinately
      regulates, MuRF-1 expression. In cultured myotubes or human embryonic kidney
      cells, MuRF-1 mRNA content and promoter activity were increased by FoxO3 but not
      by SMAD3 overexpression. However, FoxO3 and SMAD3 coexpression synergistically
      increased MuRF-1 mRNA and promoter activity. Mutation of the SMAD-binding element
      (SBE) in the proximal MuRF-1 promoter or overexpression of a SMAD3 DNA-binding
      mutant attenuated FoxO3-dependent MuRF-1 promoter activation, showing that SMAD
      binding to DNA is required for optimal activation of FoxO3-induced transcription
      of MuRF-1. Using chromatin immunoprecipitation, SMAD3 DNA binding increased FoxO3
      abundance and SBE mutation reduced FoxO3 abundance on the MuRF-1 promoter.
      Furthermore, SMAD3 overexpression dose-dependently increased FoxO3 protein
      content, and coexpression of FoxO3 and SMAD3 synergistically increased FoxO
      dependent gene transcription [assessed with a FoxO response element (FRE)-driven
      reporter]. Collectively, these results show that SMAD3 regulates transcription of
      MuRF-1 by increasing FoxO3 binding at a conserved FRE-SBE motif within the
      proximal promoter region, and by increasing FoxO3 protein content and
      transcriptional activity. These data are the first to indicate that two major
      transcription factors regulating protein degradation, FoxO3 and SMAD3, converge
      to coordinately and directly regulate transcription of MuRF-1. 

PMID- 24920683
TI  - NICE should publish numbers needed to treat and harm for statins.

PMID- 24920682
TI  - A critical assessment of two real-time PCR assays targeting the (SSU) rRNA and
      gdh genes for the molecular identification of Giardia intestinalis in a clinical
      laboratory.
AB  - INTRODUCTION: Giardiasis is an intestinal diarrhoeal illness caused by the
      flagellate protozoan parasite Giardia intestinalis. Molecular techniques for the
      identification of G. intestinalis have generally been shown to offer a better
      detection rate of the parasite than the traditional faecal concentration and
      microscopy techniques. AIM: The aim of this study was to critically assess the
      performance of a commercial and a published real-time PCR assay for their
      potential use as frontline tests for the diagnosis of giardiasis. METHODS: A
      composite reference standard of enzyme immunoassay and rapid membrane test was
      used in a diagnostic accuracy study to assess the performance of Primerdesign's,
      and Verweij et al G. intestinalis real-time PCR assays, comparing them with the
      traditional ova, cysts and parasite microscopy test (OCP-M). RESULTS: The Verweij
      real-time PCR used primers for the (SSU) rRNA gene, and produced a diagnostic
      sensitivity of 93.4% (95% CI 88.30% to 98.50%) and an efficiency of 100%.
      Primerdesign's real-time PCR used primers for the glutamate dehydrogenase gene
      and produced a diagnostic sensitivity of 61.5% (95% CI 51.50% to 71.50%) and an
      efficiency of 203%. The OCP-M sensitivity was 83.5% (95% CI 75.87% to 91.13%).
      CONCLUSIONS: The Verweij real-time PCR was robust and the most sensitive assay
      suited for use as a first-line diagnostic test for giardiasis.

PMID- 24920684
TI  - Doctors' financial interests: what about a publicly available list held by the
      GMC?

PMID- 24920685
TI  - Urgent need to establish the true incidence of the side effects of statins.

PMID- 24920686
TI  - (Mis)interpreting studies on the adverse effects of statins.

PMID- 24920687
TI  - Muscular adverse effects are common with statins.

PMID- 24920688
TI  - Colorectal cancer metastases: evaluate current practice before introducing the
      "next new thing".

PMID- 24920689
TI  - Who pays for this conference? It's time patients and doctors knew.

PMID- 24920690
TI  - Boys in the UK should be offered vaccination against human papillomavirus (HPV).

PMID- 24920691
TI  - The proportion of true cases of autism is not changing.

PMID- 24920692
TI  - The BMJ should extend its transparency protocol in light of example of King's
      Fund report on Canterbury, New Zealand.

PMID- 24920693
TI  - King's Fund reply to Gauld and colleagues.

PMID- 24920694
TI  - Scottish public health conference was cancelled after Nestle emerged as sponsor.

PMID- 24920695
TI  - End top-down changes to NHS, says think tank.

PMID- 24920696
TI  - India's health minister commits government to improving healthcare access.

PMID- 24920697
TI  - Massachusetts may be nearing universal health coverage, preliminary data show.

PMID- 24920699
TI  - Open letter raises concerns about NICE guidance on statins.

PMID- 24920700
TI  - Physicians show strong leadership in US accountable care organizations but
      surgeons are largely left out.

PMID- 24920698
TI  - Ceramide changes the mediator of flow-induced vasodilation from nitric oxide to
      hydrogen peroxide in the human microcirculation.
AB  - RATIONALE: Mitochondrial-derived hydrogen peroxide (H2O2) regulates flow-induced
      dilation (FID) in microvessels from patients with coronary artery disease. The
      relationship between ceramide, an independent risk factor for coronary artery
      disease and a known inducer of mitochondrial reactive oxygen species, and FID is
      unknown. OBJECTIVE: We examined the hypothesis that exogenous ceramide induces a
      switch in the mediator of FID from nitric oxide to H2O2. METHODS AND RESULTS:
      Internal diameter changes of resistance arterioles from human adipose and atrial
      tissue were measured by video microscopy. Mitochondrial H2O2 production was
      assayed in arterioles using mito peroxy yellow 1. Polyethylene glycol-catalase,
      rotenone, and Mito-TEMPO impaired FID in healthy adipose arterioles pretreated
      with ceramide, whereas N(omega)-nitro-l-arginine methyl ester had no effect.
      Mitochondrial H2O2 production was induced in response to flow in healthy adipose
      vessels pretreated with ceramide, and this was abolished in the presence of
      polyethylene glycol-catalase. Immunohistochemistry demonstrated ceramide
      accumulation in arterioles from both healthy patients and patients with coronary
      artery disease. N(omega)-nitro-l-arginine methyl ester reduced vasodilation to
      flow in adipose as well as atrial vessels from patients with coronary artery
      disease incubated with GW4869, a neutral sphingomyelinase inhibitor, whereas
      polyethylene glycol-catalase had no effect. CONCLUSIONS: Our data indicate that
      ceramide has an integral role in the transition of the mediator of FID from
      nitric oxide to mitochondrial-derived H2O2 and that inhibition of ceramide
      production can revert the mechanism of dilation back to nitric oxide. Ceramide
      may be an important target for preventing and treating vascular dysfunction
      associated with atherosclerosis.

PMID- 24920701
TI  - No need for urgent action on EMS, says RCVS.

PMID- 24920702
TI  - BVA will not be supporting legal challenge to pilot badger culls.

PMID- 24920703
TI  - Welfare at time of killing regulations withdrawn.

PMID- 24920704
TI  - Call for the creation of an international panel on antimicrobial resistance.

PMID- 24920705
TI  - Students get their teeth into dental techniques.

PMID- 24920706
TI  - Veterinary nurse suspended for dishonestly creating prescriptions.

PMID- 24920707
TI  - Encouraging peer support in veterinary schools.

PMID- 24920708
TI  - Involving practitioners in TB eradication.

PMID- 24920709
TI  - Badger culling: Defra gives details of gassing trials.

PMID- 24920710
TI  - Posthumous recognition for army dog's 'lifesaving bravery in conflict'.

PMID- 24920711
TI  - RCVS Knowledge seeks funds to digitise its archive collection.

PMID- 24920712
TI  - Emerging infectious diseases: opportunities at the human-animal-environment
      interface.

PMID- 24920713
TI  - The value of clinical pathology in pet rabbit medicine.

PMID- 24920715
TI  - Diagnosis of resistance to triclabendazole.

PMID- 24920716
TI  - Chlamydia in cases of bovine abortion in Ireland.

PMID- 24920717
TI  - Prestun checks and mis-stuns during conventional slaughter: welfare at slaughter.

PMID- 24920719
TI  - Diclofenac and vulture populations.

PMID- 24920720
TI  - Diclofenac and vulture populations.

PMID- 24920721
TI  - Epigenome-wide association study of fasting blood lipids in the Genetics of Lipid
      lowering Drugs and Diet Network study.
AB  - BACKGROUND: Genetic research regarding blood lipids has largely focused on DNA
      sequence variation; few studies have explored epigenetic effects. Genome-wide
      surveys of DNA methylation may uncover epigenetic factors influencing lipid
      metabolism. METHODS AND RESULTS: To identify whether differential methylation of
      cytosine-(phosphate)-guanine dinucleotides (CpGs) correlated with lipid
      phenotypes, we isolated DNA from CD4+ T cells and quantified the proportion of
      sample methylation at >450 000 CpGs by using the Illumina Infinium
      HumanMethylation450 Beadchip in 991 participants of the Genetics of Lipid
      Lowering Drugs and Diet Network. We modeled the percentage of methylation at
      individual CpGs as a function of fasting very-low-density lipoprotein cholesterol
      and triglycerides (TGs) by using mixed linear regression adjusted for age, sex,
      study site, cell purity, and family structure. Four CpGs (cg00574958, cg17058475,
      cg01082498, and cg09737197) in intron 1 of carnitine palmitoyltransferase 1A
      (CPT1A) were strongly associated with very-low low-density lipoprotein
      cholesterol (P=1.8*10(-21) to 1.6*10(-8)) and TG (P=1.6*10(-26) to 1.5*10(-9)).
      Array findings were validated by bisulfite sequencing. We performed quantitative
      polymerase chain reaction experiments demonstrating that methylation of the top
      CpG (cg00574958) was correlated with CPT1A expression. The association of
      cg00574958 with TG and CPT1A expression were replicated in the Framingham Heart
      Study (P=4.1*10(-14) and 3.1*10(-13), respectively). DNA methylation at CPT1A
      cg00574958 explained 11.6% and 5.5% of the variation in TG in the discovery and
      replication cohorts, respectively. CONCLUSIONS: This genome-wide epigenomic study
      identified CPT1A methylation as strongly and robustly associated with fasting
      very-low low-density lipoprotein cholesterol and TG. Identifying novel epigenetic
      contributions to lipid traits may inform future efforts to identify new treatment
      targets and biomarkers of disease risk.

PMID- 24920722
TI  - Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic
      Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes
      urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF
      23 concentrations increase markedly in chronic kidney disease and are associated
      with increased risk of clinical cardiovascular events. FGF-23 may promote atrial
      fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left
      atrial dysfunction. METHODS AND RESULTS: We tested the associations of
      circulating FGF-23 concentration with incident AF among 6398 participants in the
      Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the
      Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at
      baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and
      229 incident AF events in MESA and CHS, respectively. In multivariable Cox
      proportional hazards models, each 2-fold-higher FGF-23 concentration was
      associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95%
      confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in
      CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after
      adjustment for potential confounding characteristics, including kidney disease.
      Serum phosphate concentration was significantly associated with incident AF in
      MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31;
      P=0.023) but not CHS. In MESA, an association of low estimated glomerular
      filtration rate with incident AF was partially attenuated by adjustment for FGF
      23. CONCLUSION: Higher circulating FGF-23 concentration is associated with
      incident AF and may, in part, explain the link between chronic kidney disease and
      AF.

PMID- 24920723
TI  - Fibroblast growth factor 23: a novel key to find hidden substrates of atrial
      fibrillation?

PMID- 24920724
TI  - Structural proteins of West Nile virus are a major determinant of infectious
      particle production and fitness in astrocytes.
AB  - The molecular basis for the increased resistance of astrocytes to a non
      neuropathogenic strain of West Nile virus (WNV), WNV-MAD78, compared with the
      neuropathogenic strain WNV-NY remains unclear. Here, we demonstrated that the
      reduced susceptibility of astrocytes to WNV-MAD78 is due to a combination of both
      cellular activities as well as viral determinants. Analyses of the viral particle
      indicated that astrocyte-derived WNV-MAD78 particles were less infectious than
      those of WNV-NY. Additionally, inhibition of cellular furin-like proteases
      increased WNV-MAD78 infectious particle production in astrocytes, suggesting that
      high levels of furin-like protease activity within these cells acted in a cell-
      and strain-specific manner to inhibit WNV-MAD78 replication. Moreover, analysis
      of recombinant viruses indicated that the structural proteins of WNV-MAD78 were
      responsible for decreased particle infectivity and the corresponding reduction in
      infectious particle production compared with WNV-NY. Thus, the composition of the
      WNV virion was also a major determinant for viral fitness within astrocytes and
      may contribute to WNV propagation within the central nervous system. Whether the
      WNV-MAD78 structural genes reduce virus replication and particle infectivity
      through the same mechanism as the cellular furin-like protease activity or
      whether these two determinants function through distinct pathways remains to be
      determined.

PMID- 24920725
TI  - Coxsackievirus B3 regulates T-cell infiltration into the heart by lymphocyte
      function-associated antigen-1 activation via the cAMP/Rap1 axis.
AB  - Coxsackievirus B3 (CVB3) infection can trigger myocarditis and can ultimately
      lead to dilated cardiomyopathy. It is known that CVB3-induced T-cell infiltration
      into cardiac tissues is one of the pathological factors causing cardiomyocyte
      injury by inflammation. However, the underlying mechanism for this remains
      unclear. We investigated the mechanism of T-cell infiltration by two types of
      CVB3: the H3 WT strain and the YYFF attenuated strain. T-cell activation was
      confirmed by changes in the distribution of lymphocyte function-associated
      antigen-1 (LFA-1). Finally, we identified which viral gene was responsible for
      LFA-1 activation. CVB3 could infect and activate T-cells in vivo and in vitro,
      and activated T-cells were detected in CVB3-infected mouse hearts. LFA-1
      expressed on the surface of these T-cells had been activated through the
      cAMP/Rap1 pathway. Recombinant lentiviruses expressing VP2 of CVB3 could also
      induce LFA-1 activation via an increase in cAMP, whilst VP2 of YYFF did not.
      These results indicated that CVB3 infection increased cAMP levels and then
      activated Rap1 in T-cells. In particular, VP2, among the CVB3 proteins, might be
      critical for this activation. This VP2-cAMP-Rap1-LFA-1 axis could be a potential
      therapeutic target for treating CVB3-induced myocarditis.

PMID- 24920726
TI  - Evidence for immune activation in patients with residual hepatitis C virus RNA
      long after successful treatment with IFN and ribavirin.
AB  - Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful
      treatment of chronic hepatitis C, but the consequences of this phenomenon are
      unclear. Forty-nine patients who achieved a sustained virological response (SVR)
      after pegylated IFN and ribavirin therapy were analysed 52-66 months after the
      SVR. HCV RNA was detected in PBMCs from 18 patients (47.4 %), and PBMCs in two
      patients stained positive for non-structural protein 3 (NS3). Quantification of
      various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6,
      IL-8, IL-12, TNF-alpha and macrophage inflammatory protein 1beta were
      significantly higher in HCV-positive patients than in HCV-negative individuals.
      In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to
      be associated with immune activation.

PMID- 24920727
TI  - Role of decidual natural killer cells, interleukin-15, and interferon-gamma in
      placental development and preeclampsia.
AB  - Preeclampsia is a hypertensive, proteinuric disease that affects 5-10% of all
      pregnancies and is a leading cause of maternal and perinatal morbidity/mortality
      (Soto et al., J Matern Fetal Neonatal Med 25: 498-507, 2011). The primary
      treatment for preeclampsia still is delivery of the fetus and placenta. The
      underlying mechanisms remain elusive. One possibility is inadequate uterine
      angiogenesis/vascularity (decidualization) at the time of implantation (Torry et
      al., Am J Reprod Immunol 51: 257-268, 2004). Here, we review evidence for
      dysregulation of decidual natural killer (dNK) cells, which secrete important
      angiogenic factors during decidualization, as a contributing factor in
      preeclampsia. 

PMID- 24920728
TI  - Toll-like receptors and hypertension.
AB  - Hypertension and associated inflammatory processes that accelerate cardiovascular
      damage are regulated by the innate immune system. Toll-like receptors (TLR) are
      major components of the innate immune system that recognize endogenous damage
      associated molecular patterns to activate prominent inflammatory signaling
      including activation of nuclear factor-kappaB (NF-kappaB). However, the role of
      TLR in the etiology of hypertension is not well understood. TLR signaling is
      dependent on adaptor proteins that, along with the TLR expression patterns,
      confer specificity of the inflammatory response and its pathological targets.
      Here we review the conceptual framework of how TLR and their adaptor proteins may
      differentially affect hypertension and cardiac hypertrophy by different stimuli. 

PMID- 24920729
TI  - Exposure of mice to chronic hypoxia attenuates pulmonary arterial contractile
      responses to acute hypoxia by increases in extracellular hydrogen peroxide.
AB  - Exposing mice to a chronic hypoxic treatment (10% oxygen, 21 days) that promotes
      pulmonary hypertension was observed to attenuate the pulmonary vasoconstriction
      response to acute hypoxia (HPV) both in vivo and in isolated pulmonary arteries.
      Since catalase restored the HPV response in isolated arteries, it appeared to be
      attenuated by extracellular hydrogen peroxide. Chronic hypoxia promoted the
      detection of elevated lung superoxide, extracellular peroxide, extracellular SOD
      expression, and protein kinase G (PKG) activation [based on PKG dimerization and
      vasodilator-stimulated phosphoprotein (VASP) phosphorylation], suggesting
      increased generation of extracellular peroxide and PKG activation may contribute
      to the suppression of HPV. Aorta from mice exposed to 21 days of hypoxia also
      showed evidence for extracellular hydrogen peroxide, suppressing the relaxation
      response to acute hypoxia. Peroxide appeared to partially suppress contractions
      to phenylephrine used in the study of in vitro hypoxic responses. Treatment of
      mice with the heme precursor delta-aminolevulinic acid (ALA; 50 mg.kg(-1).day(
      1)) during exposure to chronic hypoxia was examined as a pulmonary hypertension
      therapy because it could potentially activate beneficial cGMP-mediated effects
      through promoting a prolonged protoporphyrin IX (PpIX)-elicited activation of
      soluble guanylate cyclase. ALA attenuated pulmonary hypertension, increases in
      both superoxide and peroxide, and the suppression of in vitro and in vivo HPV
      responses. ALA generated prolonged detectible increases in PpIX and PKG
      associated phosphorylation of VASP, suggesting PKG activation may contribute to
      suppression of pulmonary hypertension and prevention of alterations in
      extracellular peroxide that appear to be attenuating HPV responses caused by
      chronic hypoxia. 

PMID- 24920730
TI  - Differential regulation of GLUT1 and GLUT8 expression by hypoxia in mammary
      epithelial cells.
AB  - Glucose is a major substrate for milk synthesis and is taken up from the blood by
      mammary epithelial cells (MECs) through facilitative glucose transporters
      (GLUTs). The expression levels of GLUT1 and GLUT8 are upregulated dramatically in
      the mammary gland from late pregnancy through early lactation stages. This study
      aimed to test the hypothesis that this increase in GLUT1 and GLUT8 expression
      involves hypoxia signaling through hypoxia inducible factor-1alpha (HIF-1alpha)
      in MECs. Mouse mammary glands showed significantly more hypoxia in midpregnancy
      through early lactation stages compared with in the virgin stage, as stained by
      the hypoxia marker pimonidazole HCl. Treatment with hypoxia (2% O2) significantly
      stimulated glucose uptake and GLUT1 mRNA and protein expression, but decreased
      GLUT8 mRNA expression in bovine MECs. In MECs, hypoxia also increased the levels
      of HIF-1alpha protein in the nuclei, and siRNA against HIF-1alpha completely
      abolished the hypoxia-induced upregulation of GLUT1, while having no effect on
      GLUT8 expression. A 5'-RCGTG-3' core HIF-1alpha binding sequence was identified
      3.7 kb upstream of the bovine GLUT1 gene, and HIF-1alpha binding to this site was
      increased during hypoxia. In conclusion, the mammary glands in pregnant and
      lactating animals are hypoxic, and MECs respond to this hypoxia by increasing
      GLUT1 expression and glucose uptake through a HIF-1alpha-dependent mechanism.
      GLUT8 expression, however, is negatively regulated by hypoxia through a HIF
      1alpha-independent pathway. The regulation of glucose transporters through
      hypoxia-mediated gene transcription in the mammary gland may provide an important
      physiological mechanism for MECs to meet the metabolic demands of mammary
      development and lactation. 

PMID- 24920732
TI  - Effects of peripheral and spinal kappa-opioid receptor stimulation on the
      exercise pressor reflex in decerebrate rats.
AB  - The exercise pressor reflex is greater in rats with ligated femoral arteries than
      it is in rats with freely perfused femoral arteries. The exaggerated reflex in
      rats with ligated arteries is attenuated by stimulation of MU-opioid and delta
      opioid receptors on the peripheral endings of thin-fiber muscle afferents. The
      effect of stimulation of kappa-opioid receptors on the exercise pressor reflex is
      unknown. We tested the hypothesis that stimulation of kappa-opioid receptors
      attenuates the exercise pressor reflex in rats with ligated, but not freely
      perfused, femoral arteries. The pressor responses to static contraction were
      compared before and after femoral arterial or intrathecal injection of the kappa
      opioid receptor agonist U62066 (1, 10, and 100 MUg). Femoral arterial injection
      of U62066 did not attenuate the pressor responses to contraction in either group
      of rats. Likewise, intrathecal injection of U62066 did not attenuate the pressor
      response to contraction in rats with freely perfused femoral arteries. In
      contrast, intrathecal injection of 10 and 100 MUg of U62066 attenuated the
      pressor response to contraction in rats with ligated femoral arteries, an effect
      that was blocked by prior intrathecal injection of the kappa-opioid receptor
      antagonist nor-binaltorphimine. In rats with ligated femoral arteries, the
      pressor response to stimulation of peripheral chemoreceptors by sodium cyanide
      was not changed by intrathecal U62066 injections, indicating that these
      injections had no direct effect on the sympathetic outflow. We conclude that
      stimulation of spinal, but not peripheral, kappa-opioid receptors attenuates the
      exaggerated exercise pressor reflex in rats with ligated femoral arteries. 

PMID- 24920731
TI  - Elevated maternal cortisol leads to relative maternal hyperglycemia and increased
      stillbirth in ovine pregnancy.
AB  - In normal pregnancy, cortisol increases; however, further pathological increases
      in cortisol are associated with maternal and fetal morbidities. These experiments
      were designed to test the hypothesis that increased maternal cortisol would
      increase maternal glucose concentrations, suppress fetal growth, and impair
      neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg.kg(-1).day(
      1)) from day 115 of gestation to term; maternal glucose, insulin, ovine placental
      lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), beta
      hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol
      increased maternal glucose concentration and slowed the glucose disappearance
      after injection of glucose; maternal infusion of cortisol also increased the
      incidence of fetal death at or near parturition. The design of the study was
      altered to terminate the study prior to delivery, and post hoc analysis of the
      data was performed to test the hypothesis that maternal metabolic factors predict
      the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma
      insulin was increased relative to control ewes or cortisol-infused ewes with live
      lambs. Maternal cortisol infusion did not alter maternal food intake or plasma
      NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did
      not alter fetal body weight, ponderal index, or fetal organ weights. Our study
      suggests that the adverse effect of elevated maternal cortisol on pregnancy
      outcome may be related to the effects of cortisol on maternal glucose
      homeostasis, and that chronic maternal stress or adrenal hypersecretion of
      cortisol may create fetal pathophysiology paralleling some aspects of maternal
      gestational diabetes. 

PMID- 24920733
TI  - Apolipoprotein A-I mimetic peptide 4F attenuates kidney injury, heart injury, and
      endothelial dysfunction in sepsis.
AB  - Kidney injury, heart injury, and cytokine-induced vascular hyperpermeability are
      associated with high rates of morbidity and mortality in sepsis. Although the
      mechanism remains unknown, apolipoprotein A-I (apoA-I) mimetic peptide 4F reduces
      inflammation and protects HDL levels, which are reduced in sepsis. We
      hypothesized that 4F also protects kidneys and hearts in a rat model of cecal
      ligation and puncture (CLP). We divided Wistar rats into groups: sham-operated
      (control), CLP, and CLP+4F (10 mg/kg body wt ip, 6 h after CLP). At 24 h post
      CLP, we evaluated cardiac function, mean arterial pressure (MAP), heart rate
      (HR), baroreflex sensitivity, total cholesterol, LDL, HDL, serum cytokines, and
      inulin clearance. We performed immunoblotting for protein regulators of vascular
      permeability (Slit2 and Robo4) and endothelial nitric oxide synthase (eNOS) in
      kidney tissue. We evaluated heart mitochondria with electron microscopy. Although
      there was no difference in MAP, the HR was significantly higher in CLP rats than
      in control and CLP+4F rats. In CLP+4F rats, baroreflex sensitivity and cardiac
      function were completely protected from the effects of CLP, as was glomerular
      filtration; heart mitochondria morphology was improved; sepsis-induced changes in
      serum cholesterol, LDL, HDL, and apoA-I were less common; all cytokines were
      lower than in CLP rats; and expression of Slit2, Robo4, and eNOS was completely
      restored. Administration of 4F inhibits inflammatory responses and strengthens
      the vascular barrier, protecting kidneys and hearts in an HDL-dependent manner.
      To determine the extent of the protective effect of 4F, further studies are
      needed. 

PMID- 24920734
TI  - Modulation of sheep ruminal urea transport by ammonia and pH.
AB  - Ruminal fermentation products such as short-chain fatty acids (SCFA) and CO2
      acutely stimulate urea transport across the ruminal epithelium in vivo, whereas
      ammonia has inhibitory effects. Uptake and signaling pathways remain obscure. The
      ruminal expression of SLC14a1 (UT-B) was studied using polymerase chain reaction
      (PCR). The functional short-term effects of ammonia on cytosolic pH (pHi) and
      ruminal urea transport across native epithelia were investigated using pH
      sensitive microelectrodes and via flux measurements in Ussing chambers. Two
      variants (UT-B1 and UT-B2) could be fully sequenced from ovine ruminal cDNA.
      Functionally, transport was passive and modulated by luminal pH in the presence
      of SCFA and CO2, rising in response to luminal acidification to a peak value at
      pH 5.8 and dropping with further acidification, resulting in a bell-shaped curve.
      Presence of ammonia reduced the amplitude, but not the shape of the relationship
      between urea flux and pH, so that urea flux remained maximal at pH 5.8. Effects
      of ammonia were concentration dependent, with saturation at 5 mmol/l. Clamping
      the transepithelial potential altered the inhibitory potential of ammonia on urea
      flux. Ammonia depolarized the apical membrane and acidified pHi, suggesting that,
      at physiological pH (< 7), uptake of NH4 (+) into the cytosol may be a key
      signaling event regulating ruminal urea transport. We conclude that transport of
      urea across the ruminal epithelium involves proteins subject to rapid modulation
      by manipulations that alter pHi and the cytosolic concentration of NH4 (+).
      Implications for epithelial and ruminal homeostasis are discussed. 

PMID- 24920735
TI  - Renal neurohormonal regulation in heart failure decompensation.
AB  - Decompensation in heart failure occurs when the heart fails to balance venous
      return with cardiac output, leading to fluid congestion and contributing to
      mortality. Decompensated heart failure can cause acute kidney injury (AKI), which
      further increases mortality. Heart failure activates signaling systems that are
      deleterious to kidneys such as renal sympathetic nerve activity (RSNA), renin
      angiotensin-aldosterone system, and vasopressin secretion. All three reduce renal
      blood flow (RBF) and increase tubular sodium reabsorption, which may increase
      renal oxygen consumption causing AKI through renal tissue hypoxia. Vasopressin
      contributes to venous congestion through aquaporin-mediated water retention.
      Additional water retention may be mediated through vasopressin-induced medullary
      urea transport and hyaluronan but needs further study. In addition, there are
      several systems that could protect the kidneys and reduce fluid retention such as
      natriuretic peptides, prostaglandins, and nitric oxide. However, the effect of
      natriuretic peptides and nitric oxide are blunted in decompensation, partly due
      to oxidative stress. This review considers how neurohormonal signaling in heart
      failure drives fluid retention by the kidneys and thus exacerbates
      decompensation. It further identifies areas where there is limited data, such as
      signaling systems 20-HETE, purines, endothelin, the role of renal water retention
      mechanisms for congestion, and renal hypoxia in AKI during heart failure. 

PMID- 24920738
TI  - [Primary CNS lymphoma: an update on its diagnosis and management].

PMID- 24920739
TI  - [Characteristics of cerebral aneurysm clips based on measurements of the opening
      pressures: basic research using a high-pressure perfusion circuit and a porcine
      vessel].
AB  - BACKGROUND: The closing force of cerebral aneurysm clips is measured according to
      International Organization for Standardization guidelines. However, it is
      difficult to predict the risk of a clip using only the closing force. To
      investigate the clips' detailed characteristics and assess their limits, we used
      a high-pressure perfusion circuit and measured the critical pressure to the
      slipping point. METHODS: Opening pressures were measured for 3 types of Sugita
      clips using a high-pressure perfusion circuit and a porcine vessel. The opening
      pressures at different points on various blade lengths and shapes were also
      measured. RESULTS: The opening pressure of a short blade clip was higher than
      that of a long one. In a straight blade of the same length, the opening pressure
      of the proximal segment of a blade was higher than that at the distal segment.
      CONCLUSIONS: Our study showed the characteristics of various clips, such as blade
      length. These findings suggested that clips should be chosen on a case-by-case
      basis.

PMID- 24920740
TI  - [Determining the tumor-cell density required for macroscopic observation of 5-ALA
      induced fluorescence of protoporphyrin IX in cultured glioma cells and clinical
      cases].
AB  - We investigated the association between the cell density and intensity of 5
      aminolevulinic acid-induced fluorescence of protoporphyrin IX in 3-dimensionally
      cultured C6 glioma cells. The ratio between 636-nm red fluorescence excited by a
      405-nm laser and 513-nm green autofluorescence of the tissue was measured as the
      fluorescence intensity. A ratio exceeding 0.68 was macroscopically judged as
      fluorescence-positive by observers, and the cell density at this fluorescence
      intensity was 1*107< cells/mL. In clinical surgical fields, the fluorescence
      ratio was about 0.65 in cases judged as fluorescence-positive, similarly to that
      in cultured cells. Neurosurgeons and pathologists should recognize that tumor
      cells are present in fluorescence-negative regions. It is necessary to develop a
      device which measures fluorescence more simply than macroscopic observation for
      cutting-edge brain surgery.

PMID- 24920741
TI  - [Timing of helicopter transportation for patients presenting with subarachnoid
      hemorrhage on isolated islands].
AB  - Cerebral aneurysm re-rupture following subarachnoid hemorrhage(SAH)is a serious
      problem that is related with poor outcome. It is generally said that re-rupture
      occurs within 6 hours of the initial SAH;in the acute stage, strict management is
      needed even in the period before hospitalization. The aim of this study was to
      confirm whether patients on isolated islands should be transferred by helicopter
      > 6 hours after the initial SAH. Here we reviewed 125 cases of SAH in the
      isolated islands of Nagasaki prefecture between January 2007 and December 2012
      who were transferred to Nagasaki Medical Center by helicopter as a result of
      consultation via TeleStroke(41 men, 84 women;mean age, 65.76 years). Re-rupture
      was observed in seven patients(5.6%), five of whom were diagnosed with re-rupture
      in a prior hospital on the isolated island. No patients demonstrated clinical
      deterioration during transport. Early helicopter transportation under adequate
      sedation and control of blood pressure within 6 hours is safe, and patients
      should be transferred as quickly as possible during the day. On the other hand,
      at night, flight safety must first be considered. Patients in stable clinical
      condition may be transferred the next day. We should pay special attention to
      patients with SAH and intracerebral hemorrhage, severe SAH, or vertebral artery
      dissecting aneurysm because their condition may gradually become more serious
      even if initially stable. 

PMID- 24920742
TI  - [Pediatric medulloblastoma presenting as cerebellar hemorrhage: a case report].
AB  - Medulloblastomas usually cause cerebellar ataxia and acute hydrocephalus owing to
      their increase in size. Cerebellar hemorrhage is an extremely rare initial
      clinical presentation of medulloblastoma. Herein, we report a case of
      medulloblastoma in an 8-year-old girl who presented with initial cerebellar
      intratumoral hemorrhage. The patient initially presented with mild headache;the
      differential diagnosis by using the initial computed tomography and magnetic
      resonance images was difficult, as bleeding from a cerebellar vascular
      malformation(cavernous angioma or arteriovenous malformation)was considered more
      likely. Hydrocephalus or typical findings indicative of medulloblastoma were not
      observed. We initially only observed the patient at another institution because
      the hematoma was relatively small(1.5*1*1cm). After follow-up imaging for
      pathological diagnosis, surgical removal was performed at our institute 49 days
      after the hemorrhage was observed. Complete tumor removal was achieved, and the
      histopathological diagnosis was medulloblastoma. The patient received whole brain
      and spinal irradiation(23.4Gy;posterior fossa local:50.4Gy)and
      chemotherapy(cyclophosphamide, 1,000mg/m2/day on day 1;vincristine, 1.5mg/m2/day
      on day 1;etoposide, 100mg/m2/day on days 1-3;cisplatin, 90mg/m2/day on day 2). No
      recurrences or neurological deficits were observed during a 2-year follow-up.
      This was a rare case of medulloblastoma presenting as cerebellar hemorrhage.
      Cerebellar medulloblastoma is among the common pediatric brain tumors;therefore,
      it should be diagnosed accurately and quickly.

PMID- 24920743
TI  - [A case of lateral ventricle metastasis from gastric carcinoma].
AB  - Metastatic brain tumors of the lateral ventricles are rare. Approximately half of
      the reported cases have originated from renal carcinoma;to the best of our
      knowledge, only 1 case originating from gastric carcinoma has been reported. A 57
      year-old man presented with dull headache, left hemiparesis, and constructional
      apraxia of the right upper extremity. He had undergone gastrectomy for gastric
      carcinoma 8 years previously. Magnetic resonance imaging revealed an enhanced
      tumor extending from the right caudate nucleus to the right lateral ventricle
      with peritumoral edema. Complete resection of the tumor was achieved via the
      right transcallosal approach. The histopathological diagnosis was metastasis from
      the gastric carcinoma. After the resection, the patient temporarily showed a lack
      of spontaneity and extrapyramidal signs of the right upper and lower limbs;his
      condition improved after 3 weeks. He was discharged 2 months after the surgery,
      without any neurological deficits. Patients with tumors of the lateral ventricles
      may present with various characteristic neurological symptoms in the
      perioperative period;therefore, a thorough neurological examination is necessary.

PMID- 24920744
TI  - [A case of possible immunoglobulin G4-related disease (IgG4-RD) with
      retroperitoneal fibrosis and central diabetes insipidus due to
      infundibulohypophysitis].
AB  - We report a case of possible immunoglobulin G4-related disease(IgG4-RD)that
      resulted in complications such as retroperitoneal fibrosis and
      infundibulohypophysitis. The patient was a 72-year-old male who presented with
      polyuria and polydipsia. Magnetic resonance imaging(MRI)revealed a thickened
      pituitary stalk and contrast enhancement with gadolinium. T1-weighted imaging
      revealed that the posterior pituitary high-signal zone had disappeared. Central
      diabetes insipidus was diagnosed on the basis of results of the hypertonic saline
      test. In addition, pressure due to retroperitoneal fibrosis resulted in
      hydronephrosis and elevated serum IgG4 levels. Because it was determined that the
      patient could have IgG4-RD, he was administered prednisolone, following which a
      decrease in the size of the pituitary stalk and retroperitoneal fibrosis was
      observed. IgG4-RD is characterized by elevated serum IgG4 levels and the
      infiltration of IgG4-positive plasma cells into various organs, including the
      central nervous system. Recently, IgG4-RD research teams organized by the
      Ministry of Health, Labour and Welfare established guidelines for the diagnosis
      of IgG4-RD. According to these guidelines, this case would fall under the
      category of "possible IgG4-RD." This case suggested that when
      infundibulohypophysitis is detected by neuroradiology, further investigation into
      the possibility of IgG4-RD should be recommended. 

PMID- 24920745
TI  - [Successful recanalization of intracranial internal carotid artery occlusion by
      rapidly changing from the Penumbra System(r) to the Merci(r) Retrieval System to
      retrieve a predicted white thrombus: a case report].
AB  - This report describes a case of successful recanalization of intracranial
      internal carotid artery occlusion by rapidly changing from the Penumbra System(r)
      to the Merci(r) Retrieval System for the retrieval of a predicted white thrombus.
      A 72-year-old man was consulted to our department with a consciousness
      disturbance. The patient had undergone graft placement for the management of a
      thoracic aortic aneurysm 14 days prior. Neurological examination revealed left
      sided severe motor weakness and dysarthria. Magnetic resonance(MR)imaging showed
      a cerebral infarction in the territory of the right internal carotid artery(ICA),
      while MR angiography revealed occlusion of the right ICA. The systemic
      intravenous injection of recombinant tissue plasminogen activator was
      contraindicated, so a mechanical thrombectomy was performed. The use of the
      Penumbra System(r) failed to achieve recanalization of the right ICA;therefore,
      revascularization using the Merci(r) Retrieval System was performed. As a result,
      complete recanalization was achieved approximately 2 hours and 45 minutes after
      symptom onset. The retrieved specimen was elastic and hard, and histological
      examination revealed a white thrombus without endovascular organization.
      Postoperatively, the patient was restless for 1 day but did not show any
      neurological abnormalities. His postoperative course was uneventful, and he was
      discharged 7 days later without any neurological deficits. 

PMID- 24920746
TI  - [Bilateral internal carotid artery lesions associated with persistent primitive
      trigeminal artery].

PMID- 24920747
TI  - [Required knowledge for spinal surgeon(10)carpal tunnel syndrome].

PMID- 24920748
TI  - Nitrergic Pathway Is the Major Mechanism for the Effect of DA-9701 on the Rat
      Gastric Fundus Relaxation.
AB  - BACKGROUND/AIMS: DA-9701 significantly improved gastric accommodation by
      increasing the postprandial gastric volume. In this study, we investigated how DA
      9701 affects the rat gastric fundus relaxation. METHODS: Gastric fundus muscle
      strips (9 longitudinal and 7 circular muscles) were obtained from rats.
      Electrical field stimulation (EFS) was performed at various frequencies (1, 5, 10
      and 20 Hz) and train durations (1, 5, 10 and 20 seconds) to select optimal
      condition for experiments. Isometric force measurements were performed in
      response to EFS. Peak and nadir were observed during the first 1 minute after
      initiation of EFS in control state and after sequential addition of atropine (1
      MUM), DA-9701 (0.5, 5, 25 and 50 MUg), N-nitro-L-arginine (L-NNA, 100 MUM),
      MRS2500 (1 MUM) and tetrodotoxin (TTX, 1 MUM) to the organ bath. RESULTS: The
      optimal frequency and duration of EFS to evoke nerve-mediated relaxation was
      determined as 5 Hz for 10 seconds. Addition of L-NNA in the presence of atropine
      and DA-9701 (50 MUg) decreased nadir by inhibiting relaxation from -0.054 +/-
      0.021 g to -0.022 +/- 0.015 g (P = 0.026) in longitudinal muscles. However,
      subsequent application of MRS2500 in the presence of atropine, DA-9701 (50 MUg)
      and L-NNA did not affect nadir. In circular muscles, subsequent addition of L-NNA
      and MRS2500 in the presence of atropine and DA-9701 (50 MUg) did not show
      significant change of nadir. CONCLUSIONS: Our data suggest that the effect of DA
      9701 on the rat gastric fundus relaxation is mainly mediated by nitrergic rather
      than purinergic pathway.

PMID- 24920749
TI  - Vitellogenin RNAi halts ovarian growth and diverts reproductive proteins and
      lipids in young grasshoppers.
AB  - Reduced reproduction extends lifespan of females in many animals. To test the
      effects of reproduction on storage of macronutrients, we block reproductive
      output in the lubber grasshopper by injecting RNAi against the precursor to egg
      yolk protein, vitellogenin, in early adulthood. Controls were injected with
      either buffer or RNAi against the major storage protein in the hemolymph,
      hexamerin-90. Vitellogenin RNAi greatly reduced both levels of mRNA for
      vitellogenin and ovarian growth, in comparison to both controls. Fat body mass
      was increased upon vitellogenin RNAi, but concentrations of the three hexameric
      storage proteins from the hemolymph were not. Surprisingly, hemolymph
      vitellogenin levels were increased upon vitellogenin RNAi. Total reproductive
      protein (hemolymph vitellogenin plus ovarian vitellin) was unchanged by
      vitellogenin RNAi, as reproductive protein was diverted to the hemolymph.
      Similarly, the increased lipid storage upon vitellogenin RNAi was largely
      attributable to the reduction in lipid in the ovary, due to decreased ovarian
      growth. A BLAST search revealed that the 515 bp sequence of vitellogenin used for
      RNAi had three 11 bp regions identical to the vitellogenin receptor of the
      cockroach Leucophaea maderae. This suggests that our treatment, in addition to
      reducing levels of vitellogenin transcript, may have also blocked transport of
      vitellogenin from the hemolymph to the ovary. This would be consistent with
      halted ovarian growth simultaneous with high levels of vitellogenin in the
      hemolymph. Nonetheless, the accumulation of vitellogenin, instead of hexameric
      storage proteins, is inconsistent with a simple model of the trade-off between
      reproduction and storage. This was observed in young females; future studies will
      address whether investment of proteins may shift to the soma as individuals age.
      Overall, our results suggest that blockage of reproduction in young grasshoppers
      redirects lipids to storage and reproductive proteins to the hemolymph. 

PMID- 24920750
TI  - Insights from stable isotopic tracers on reproductive allocation under stress.
AB  - Fecundity is affected by changes in the nutritional and energetic environment, as
      a result of changes in acquisition, assimilation, or allocation of macro
      nutrients and micro-nutrients. Stable isotopes of carbon and nitrogen offer a
      window into the processes underlying these changes. In insects that feed on
      nectar as adults, carbon isotopes can be used to trace allocation of carbon to
      eggs from larval (capital) and adult (income) sources. If adults are fed sugar
      water, there is no source of nitrogen from the adult diet. Thus, nitrogen
      isotopes in eggs reflect fractionation of larval nitrogen due to protein
      catabolism and anabolism. We subjected adult females of two butterfly species,
      Speyeria mormonia and Colias eurytheme, to dietary restriction (DR), larval
      female S. mormonia to DR, and adult female S. mormonia to extra flight. Females
      subjected to extra flight were previously found to eat more as adults and to have
      a higher resting metabolic rate. As predicted, significantly less carbon obtained
      by feeding as adults was incorporated into eggs in both species under DR when
      adult. Speyeria mormonia eggs contained significantly more carbon derived from
      adult feeding under DR as larvae and when subjected to extra flight as adult
      females. Again as predicted, eggs from females of both species subjected to DR
      when adults were enriched for (15)N, suggesting that increased protein catabolism
      or anabolism generated additional carbon compounds. Speyeria mormonia eggs from
      females subjected to DR when larvae or to additional flight as adults were
      depleted for (15)N. The result for DR of larvae suggests minimization of protein
      catabolism when protein reserves are relatively scarce. The results for flight
      were not as predicted, and deserve further exploration. In most cases, isotopic
      signature in eggs changed with females' age. Eggs were progressively more
      enriched for the carbon signature of adults, consistent with a two-compartment
      mixing model for the carbon sources of larvae and adults. Eggs laid across the
      life of a female were progressively depleted for (15)N, followed by
      stabilization. This could be due to high total investment in eggs early in life,
      as the results are consistent with those for other growing animals. Overall,
      these results indicate shifts in allocation of incoming and stored (capital)
      carbon in response to various environmental stresses. The results for nitrogen
      suggest hypotheses to be tested concerning nitrogen metabolism under
      environmental stress. 

PMID- 24920751
TI  - The Drosophila egg chamber-a new spin on how tissues elongate.
AB  - During development, tissues undergo complex cellular rearrangements and changes
      in shape that produce a diversity of body plans and the functional organs
      therein. The Drosophila egg chamber has emerged as an exciting and highly
      tractable model in which to investigate novel mechanisms driving the elongation
      of tissues. Egg chambers are multicellular assemblies within flies' ovaries that
      will each give rise to a single egg. Although initially spherical, these simple
      organ-like structures lengthen as they grow. This transformation depends on an
      unusual form of planar polarity in the egg chamber's outer epithelial layer, in
      which arrays of linear actin bundles and fibril-like structures in the basement
      membrane both align perpendicular to the axis of elongation. The resulting
      circumferential arrangement of structural molecules is then thought to act as a
      "molecular corset" that directionally biases growth of the egg chamber. I will
      explore four fundamental questions about this system: (1) How is the
      circumferential pattern generated in the follicular epithelium? (2) What is the
      physical nature of the corset? (3) How does a corset-type mechanism lead to the
      cellular rearrangements necessary for the elongation of tissues? and (4) To what
      extent are the cellular mechanisms controlling egg chamber elongation conserved
      in other systems? For each topic, I will present insights gleaned from the recent
      literature and highlight fertile areas for future investigation. 

PMID- 24920752
TI  - Does thermal ecology influence dynamics of side-blotched lizards and their micro
      parasites?
AB  - Hosts and parasites form interacting populations that influence each other in
      multiple ways. Their dynamics can also be influenced by environmental and
      ecological factors. We studied host-parasite dynamics in a previously unexplored
      study system: side-blotched lizards and their micro-parasites. Compared with
      uninfected lizards, the infected lizards elected to bask at lower temperatures
      that were outside their range of preferred temperatures. Infected lizards also
      were not as precise as uninfected lizards in maintaining their body temperatures
      within a narrow range. At the ecological scale, areas with higher infection rates
      coincided with more thermally heterogeneous microhabitats as well as with the
      areas where lizards tended to live longer. Thermal heterogeneity of lizards'
      microhabitats may provide important clues to the spatial and temporal
      distribution of infections. 

PMID- 24920753
TI  - Blockade of cysteine-rich protein 61 attenuates renal inflammation and fibrosis
      after ischemic kidney injury.
AB  - Emerging data have suggested that acute kidney injury (AKI) is often incompletely
      repaired and can lead to chronic kidney disease (CKD), which is characterized by
      tubulointerstitial inflammation and fibrosis. However, the underlying mechanisms
      linking AKI to CKD remain obscure. The present study aimed to investigate the
      role of cysteine-rich protein 61 (Cyr61) after unilateral kidney ischemia
      reperfusion injury (IRI) in mice. After IRI, increased expression of Cyr61 was
      detected, predominately in the proximal tubular epithelium. This was confirmed by
      in vitro experiments, which showed that hypoxia stimulated Cyr61 expression in
      cultured proximal tubular epithelial cells. The proinflammatory property of Cyr61
      was indicated by its ability to upregulate monocyte chemoattractant protein-1 and
      IL-6. Additionally, we found elevated urinary Cyr61 excretion in patients with
      AKI. Notably, treatment of mice with an anti-Cyr61 antibody attenuated the
      upregulation of kidney monocyte chemoattractant protein-1, IL-6, IL-1beta, and
      macrophage inflammatory protein-2 and reduced the infiltration of F4/80-positive
      macrophages on days 7 and 14 after IRI. In addition, blockade of Cyr61 reduced
      the mRNA expression of collagen, transforming growth factor-beta, and plasminogen
      activator inhibitor-I as well as the degree of collagen fibril accumulation, as
      evaluated by picrosirius red staining, and levels of alpha-smooth muscle actin
      proteins by day 14. Concurrently, in the treated group, peritubular microvascular
      density was more preserved on day 14. We conclude that Cyr61 blockade inhibits
      the triad of inflammation, interstitial fibrosis, and capillary rarefaction after
      severe ischemic AKI. The results of this study expand the knowledge of the
      mechanisms underlying the AKI-to-CKD transition and suggest that Cyr61 is a
      potential therapeutic target. 

PMID- 24920754
TI  - WNK3 abrogates the NEDD4-2-mediated inhibition of the renal Na+-Cl-
      cotransporter.
AB  - The serine/threonine kinase WNK3 and the ubiquitin-protein ligase NEDD4-2 are key
      regulators of the thiazide-sensitive Na+-Cl- cotransporter (NCC), WNK3 as an
      activator and NEDD2-4 as an inhibitor. Nedd4-2 was identified as an interacting
      partner of WNK3 through a glutathione-S-transferase pull-down assay using the N
      terminal domain of WNK3, combined with LC-MS/MS analysis. This was validated by
      coimmunoprecipitation of WNK3 and NEDD4-2 expressed in HEK293 cells. Our data
      also revealed that the interaction between Nedd4-2 and WNK3 does not involve the
      PY-like motif found in WNK3. The level of WNK3 ubiquitylation did not change when
      NEDD4-2 was expressed in HEK293 cells. Moreover, in contrast to SGK1, WNK3 did
      not phosphorylate NEDD4-2 on S222 or S328. Coimmunoprecipitation assays showed
      that WNK3 does not regulate the interaction between NCC and NEDD4-2.
      Interestingly, in Xenopus laevis oocytes, WNK3 was able to recover the SGK1
      resistant NEDD4-2 S222A/S328A-mediated inhibition of NCC and further activate
      NCC. Furthermore, elimination of the SPAK binding site in the kinase domain of
      WNK3 (WNK3-F242A, which lacks the capacity to bind the serine/threonine kinase
      SPAK) prevented the WNK3 NCC-activating effect, but not the Nedd4-2-inhibitory
      effect. Together, these results suggest that a novel role for WNK3 on NCC
      expression at the plasma membrane, an effect apparently independent of the SPAK
      kinase and the aldosterone-SGK1 pathway.

PMID- 24920755
TI  - Angiotensin II stimulates fibronectin protein synthesis via a
      Gbetagamma/arachidonic acid-dependent pathway.
AB  - In rabbit proximal tubular cells, ANG II type 2-receptor (AT2)-induced
      arachidonic acid release is PLA2 coupled and dependent of G protein betagamma
      (Gbetagamma) subunits. Moreover, ANG II activates ERK1/2 and transactivates EGFR
      via a c-Src-dependent mechanism. Arachidonic acid has been shown to mimic this
      effect, at least in part, by an undetermined mechanism. In this study, we
      determined the effects of ANG II on fibronectin expression in cultured rabbit
      proximal tubule cells and elucidated the signaling pathways associated with such
      expression. We found that ANG II and transfection of Gbetagamma subunits directly
      increased fibronectin protein expression, and this increase was inhibited by
      overexpression of beta-adrenergic receptor kinase (betaARK)-ct or DN-Src.
      Moreover, ANG II-induced fibronectin protein expression was significantly
      abrogated by the AT2 receptor antagonist PD123319. In addition, inhibition of
      cystolic PLA2 diminished ANG II-induced fibronectin expression. Endogenous
      arachidonic acid mimicked ANG II-induced fibronectin expression. We also found
      that overexpression of Gbetagamma subunits induced c-Src, ERK1/2, and EGFR
      tyrosine phosphorylation, which can be inhibited by overexpression of betaARK-ct
      or DN-Src. Gbetagamma also induced c-Src SH2 domain association with the EGFR.
      Supporting these findings, in rabbit proximal tubular epithelium, immunoblot
      analysis indicated that betagamma expression was significant. Interestingly,
      arachidonic acid- and eicosatetraenoic acid-induced responses were preserved in
      the presence of betaARK-ct. This is the first report demonstrating the regulation
      of EGFR, ERK1/2, c-Src, and fibronectin by Gbetagamma subunits in renal
      epithelial cells. Moreover, this work demonstrates a role for Gbetagamma
      heterotrimeric proteins in ANG II, but not arachidonic acid, signaling in renal
      epithelial cells. 

PMID- 24920756
TI  - Evidence for pericyte origin of TSC-associated renal angiomyolipomas and
      implications for angiotensin receptor inhibition therapy.
AB  - Nearly all patients with tuberous sclerosis complex (TSC) develop renal
      angiomyolipomas, although the tumor cell of origin is unknown. We observed
      decreased renal angiomyolipoma development in patients with TSC2- polycystic
      kidney disease 1 deletion syndrome and hypertension that were treated from an
      early age with angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers compared with patients who did not receive this therapy. TSC-associated
      renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth
      factor receptor-beta, desmin, alpha-smooth muscle actin, and VEGF receptor 2 but
      did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of
      TSC patients exhibited increased vascular mural cell-secreted peptides, such as
      VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings
      suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of
      angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca(2+)
      response and increased proliferation, which were blocked by the ANG II type 2
      receptor antagonist valsartan. Blockade of ANG II signaling may have preventative
      therapeutic potential for angiomyolipomas. 

PMID- 24920757
TI  - Renal blood flow and oxygenation drive nephron progenitor differentiation.
AB  - During kidney development, the vasculature develops via both angiogenesis
      (branching from major vessels) and vasculogenesis (de novo vessel formation). The
      formation and perfusion of renal blood vessels are vastly understudied. In the
      present study, we investigated the regulatory role of renal blood flow and O2
      concentration on nephron progenitor differentiation during ontogeny. To elucidate
      the presence of blood flow, ultrasound-guided intracardiac microinjection was
      performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys
      were costained for the vasculature, ureteric epithelium, nephron progenitors, and
      nephron structures. We also analyzed nephron differentiation in normoxia compared
      with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were
      perfused; however, smaller-caliber peripheral vessels remained unperfused. By
      E15.5, peripheral vessels started to be perfused as well as glomeruli. While the
      interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone)
      remained unperfused. Directly adjacent and internal to the nephrogenic zone, we
      found differentiated nephron structures surrounded and infiltrated by perfused
      vessels. Furthermore, we determined that at low O2 concentration, little nephron
      progenitor differentiation was observed; at higher O2 concentrations, more
      differentiation of the nephron progenitors was induced. The formation of the
      developing renal vessels occurs before the onset of blood flow. Furthermore,
      renal blood flow and oxygenation are critical for nephron progenitor
      differentiation. 

PMID- 24920758
TI  - Predictive ability of bleeding risk scores in the routine clinical practice.
AB  - BACKGROUND: Previous predictive models of bleeding in acute coronary syndromes
      (ACSs) used different definitions of bleeding and some of them come from
      populations lacking important predictors of haemorrhagic complications. Our group
      previously developed a predictive model of bleeding (PMB), including clinically
      meaningful variables, providing an optimal predictive ability. We aimed to
      compare the ability of this PMB with the main available bleeding risk scores for
      predicting major bleeding according to different definitions in non-selected ACS
      patients from daily clinical practice. METHODS: All ACS patients admitted to the
      Coronary Care Unit were prospectively included. CRUSADE, Mehran and ACTION
      bleeding risk scores were calculated for each patient. In-hospital bleeding was
      recorded using the CRUSADE, TIMI, Mehran, ACTION and BARC definitions. For
      reasons of clinical relevance, BARC 3 and 5 categories were considered severe
      BARC bleeding for this study. The predictive ability of the PMB and other
      bleeding risk scores was assessed by binary logistic regression, ROC curves and
      areas under the curves (AUCs). RESULTS: We included 1976 patients. Mean age was
      62.1 years. Almost all patients underwent angiography, 65% of them by the radial
      approach. The incidence of major bleeding was: CRUSADE bleeding 3.9% (77/1976);
      Mehran bleeding 4.8% (94/1976); ACTION bleeding 3.9% (78/1976); and BARC 3/5
      bleeding 2.4% (48/1976). The PMB showed the best ability for predicting major
      bleeding regardless of the definition used. The differences were specially
      significant for predicting BARC 3/5 bleeding (AUC: PMB 0.87, Mehran score 0.68,
      CRUSADE score 0.70 and ACTION score 0.70). The predictive ability of CRUSADE,
      ACTION and Mehran scores was similar for all the definitions analysed.
      CONCLUSIONS: Current bleeding risk scores showed a similar predictive ability for
      major bleeding regardless of the definitions used. Including other clinically
      meaningful predictors of bleeding into the new PMB significantly improved its
      predictive ability in the clinical scenario of ACS.

PMID- 24920759
TI  - Impact of the Japan earthquake disaster with massive Tsunami on emergency
      coronary intervention and in-hospital mortality in patients with acute ST
      elevation myocardial infarction.
AB  - AIMS: The aims of this study were to evaluate reperfusion rate, therapeutic time
      course and in-hospital mortality pre- and post-Japan earthquake disaster,
      comparing patients with ST-elevation myocardial infarction (STEMI) treated in the
      inland area or the Tsunami-stricken area of Iwate prefecture. METHOD AND RESULTS:
      Subjects were 386 consecutive STEMI patients admitted to the four percutaneous
      coronary intervention (PCI) centers in Iwate prefecture in 2010 and 2011.
      Patients were divided into two groups: those treated in the inland or Tsunami
      stricken area. We compared clinical characteristics, time course and in-hospital
      mortality in both years in the two groups. PCI was performed in 310 patients
      (80.3%). Door-to-balloon (D2B) time in the Tsunami-stricken area in 2011 was
      significantly shorter than in 2010 in patients treated with PCI. However, the
      rate of PCI performed in the Tsunami-stricken area in March-April 2011 was
      significantly lower than that in March-April 2010 (41.2% vs 85.7%; p=0.03). In
      hospital mortality increased three-fold from 7.1% in March-April 2010 to 23.5% in
      March-April 2011 in the Tsunami-stricken area. Standardized mortality ratio (SMR)
      in March-April 2011 in the Tsunami-stricken area was significantly higher than
      the control SMR (SMR 4.72: 95% confidence interval (CI): 1.77-12.6: p=0.007).
      CONCLUSIONS: The rate of PCI decreased and in-hospital mortality increased
      immediately after the Japan earthquake disaster in the Tsunami-stricken area.
      Disorder in hospitals and in the distribution systems after the disaster impacted
      the clinical care and outcome of STEMI patients.

PMID- 24920760
TI  - Late driveline left ventricular assist device infection treated with frozen-and
      thawed allogeneic platelet gel.
AB  - In this case report, we report the application of frozen-and-thawed allogeneic
      platelet gel (PLT-gel) to treat a late driveline exit site infection in a 56-year
      old patient supported by a Heartware-HVAD left ventricular assist device. The
      treatment duration was 4 weeks and at the follow-up the skin around the exit site
      was free from further infection. PLT-gel can be used to treat local infection of
      the driveline exit site and to prevent further high-risk infections. 

PMID- 24920761
TI  - Do patients with haematological malignancy who need cardiopulmonary bypass have a
      short-term higher mortality or a higher chance of disease progression?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether patients with haematological
      malignancy (HM) who need cardiopulmonary bypass (CPB) have a higher short-term
      mortality or a higher chance of disease progression secondary to CPB. Altogether,
      107 papers were found using the reported search terms, but ultimately only eight
      were relevant to our subject. We found four case series and four case-control
      series. Most of the found papers were only short series. The largest series
      included 56 patients with HM and requiring CPB, suggesting that HM patients
      rarely require CPB surgery and/or are not operated on. Most of these studies
      showed that the overall postoperative morbidity rate was increased, reaching 50
      60% of the patients. These comorbidities were mainly related to postoperative
      infections, bleeding and blood transfusions, which were highly significant.
      However, in most papers, the postoperative hospital stay was not different and
      the in-hospital mortality rate of HM patients was similar to that of healthy
      patients. One paper demonstrated that the time taken before initiating
      chemotherapy was longer in patients who underwent CPB surgery. No paper reported
      an acute change in blood disorders. Long-term mortality rates were not mentioned
      in some papers, but when it was stated, the HM patients' long-term mortality
      seemed not increased by using CPB surgery, with more than 80% survival at 3 years
      and 20-25% progression of the disease at 3 years. Although these study
      limitations are linked to the low-evidence levels in some of the papers used,
      haematological malignancies should not be considered a contraindication for
      cardiac CPB surgery. 

PMID- 24920762
TI  - Nonadaptive processes governing early stages of polyploid evolution: Insights
      from a primary contact zone of relict serpentine Knautia arvensis
      (Caprifoliaceae).
AB  - * Premise of the study: Contact zones between polyploids and their diploid
      progenitors may provide important insights into the mechanisms of sympatric
      speciation and local adaptation. However, most published studies investigated
      secondary contact zones where the effects of genome duplication can be confounded
      by previous independent evolution of currently sympatric cytotypes. We compared
      genetically close diploid and autotetraploid serpentine cytotypes of Knautia
      arvensis (Caprifoliaceae) in a primary contact zone and evaluated the role of
      adaptive and nonadaptive processes for cytotype coexistence.* Methods: DNA flow
      cytometry was used to determine ploidy distribution at various spatial scales
      (from across the entire contact zone to microgeographic). Habitat preferences of
      diploids and polyploids were assessed by comparing vegetation composition of
      nearby ploidy-uniform sites and by recording plant species immediately
      surrounding both cytotypes in mixed-ploidy plots.* Key results: Tetraploids
      considerably outnumbered their diploid progenitors in the contact zone. Both
      cytotypes were segregated at all investigated spatial scales. This pattern was
      not driven by ecological shifts, because both diploids and tetraploids inhabited
      sites with nearly identical vegetation cover. Certain interploidy niche
      differentiation was indicated only at the smallest spatial scale; ecologically
      nonadaptive processes were most likely responsible for this difference.*
      Conclusions: We conclude that a shift in ecological preferences (i.e., the
      adaptive scenario) is not necessary for the establishment and evolutionary
      success of autopolyploid derivatives in primary contact zones. Spatial
      segregation that would support ploidy coexistence can also be achieved by
      ecologically nonadaptive processes, including the founder effect, limited
      dispersal ability, intense clonal growth, and triploid block.

PMID- 24920763
TI  - Seed source, seed traits, and frugivore habits: Implications for dispersal
      quality of two sympatric primates.
AB  - * Premise of the study: Frugivore selection of fruits and treatment of seeds
      together with seed deposition site are crucial for the population dynamics of
      vertebrate-dispersed plants. However, frugivore species may influence dispersal
      quality differently even when feeding on the same fruit species and, while
      animals disperse some seeds, others simply fall beneath the parent plant.*
      Methods: In southern Mexico, we investigated to see if within-species seed traits
      (i.e., length, width, weight, and volume) and germination success differed
      according to seed source. For five tropical tree species we obtained ingested
      seeds from two sources, howler monkey (Alouatta pigra) and spider monkey (Ateles
      geoffroyi) feces; and noningested seeds from two sources, the ground and tree
      crowns (with predispersed seeds used as control).* Key results: A principal
      components' analysis showed that traits of seeds ingested by howler monkeys
      differed from other sources while seeds ingested by spider monkeys were similar
      to noningested seeds. Howlers consumed on average the larger seeds in Ampelocera
      hottlei, Brosimum lactescens, and Dialium guianense. Both primate species
      consumed the smaller seeds in Spondias mombin, while no seed trait differences
      among seed sources were found in Spondias radlkoferi. For all five tree species,
      germination rate was greatest for seeds ingested by howler monkeys.* Conclusions:
      For the studied plant species, seed ingestion by howler monkeys confers higher
      dispersal quality than ingestion by spider monkeys or nondispersal. Dispersal
      services of both primate species, however, are not redundant and may contribute
      to germination heterogeneity within plant populations in tropical forests.

PMID- 24920764
TI  - Lippia alba (Verbenaceae): A new tropical autopolyploid complex?
AB  - * Premise of the study: Tropical regions have high species diversity, and
      polyploidization is a major mechanism of speciation in plants. However, few cases
      of natural polyploidy have been reported in tropical regions. Lippia alba, is a
      tropical, aromatic shrub with a wide distribution, extensive morphological
      plasticity, and several chemotypes. The species has long been recognized as a
      diploid with 2n = 30 chromosomes. Recently, two variations in chromosome number
      (2n = 60; 2n = 12-60) have been reported, suggesting the occurrence of polyploidy
      within the species.* Methods: Flow cytometry was used to investigate the genome
      size in 106 accessions from 14 Brazilian States. Conventional and molecular
      cytogenetic techniques and pollen viability analysis were employed to
      characterize each chromosome number observed.* Key results: The DNA 1C-value
      varied from 1.17 to 3.45 pg, showing a large variation in genome size. Five
      distinct chromosome numbers were observed (2n = 30, 38, 45, 60, 90); three are
      cytogenetically described here for the first time. The 5S rDNA signals varied
      proportionally according to each chromosome number, but 45S rDNA sites did not.
      High rates of meiotic irregularity were observed, mainly in cytotypes with higher
      chromosome numbers.* Conclusions: The data provide new support for the occurrence
      of a polyploid series in Lippia alba. We provide a hypothesis for how this
      complex may have arisen. Other cryptic polyploid complexes may remain
      undiscovered in tropical regions.

PMID- 24920765
TI  - Rapid detection and simultaneous antibiotic susceptibility analysis of Yersinia
      pestis directly from clinical specimens by use of reporter phage.
AB  - Yersinia pestis is a tier 1 agent due to its contagious pneumopathogenicity,
      extremely rapid progression, and high mortality rate. As the disease is usually
      fatal without appropriate therapy, rapid detection from clinical matrices is
      critical to patient outcomes. We previously engineered the diagnostic phage
      PhiA1122 with luxAB to create a "light-tagged" reporter phage. PhiA1122::luxAB
      rapidly detects Y. pestis in pure culture and human serum by transducing a
      bioluminescent signal response. In this report, we assessed the analytical
      specificity of the reporter phage and investigated diagnostic utility (detection
      and antibiotic susceptibility analysis) directly from spiked whole blood. The
      bioreporter displayed 100% (n = 59) inclusivity for Y. pestis and consistent
      intraspecific signal transduction levels. False positives were not obtained from
      species typically associated with bacteremia or those relevant to plague
      diagnosis. However, some non-pestis Yersinia strains and Enterobacteriaceae did
      elicit signals, albeit at highly attenuated transduction levels. Diagnostic
      performance was assayed in simple broth-enriched blood samples and standard
      aerobic culture bottles. In blood, <10(2) CFU/ml was detected within 5 h. In
      addition, Y. pestis was identified directly from positive blood cultures within
      20 to 45 min without further processing. Importantly, coincubation of blood
      samples with antibiotics facilitated simultaneous antimicrobial susceptibility
      profiling. Consequently, the reporter phage demonstrated rapid detection and
      antibiotic susceptibility profiling directly from clinical samples, features that
      may improve patient prognosis during plague outbreaks. 

PMID- 24920766
TI  - Multidrug-resistant nontuberculous mycobacteria isolated from cystic fibrosis
      patients.
AB  - Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of
      pulmonary infections in cystic fibrosis (CF) patients, with an estimated
      prevalence ranging from 5 to 20%. This work investigated the presence of NTM in
      sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal
      clinical supervision at a regional reference center in Rio de Janeiro, Brazil.
      From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of
      129 children were obtained. Molecular identification of NTM was performed by
      using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and
      sequencing of the rpoB gene, and susceptibility tests were performed that
      followed Clinical and Laboratory Standards Institute recommendations. For
      evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE)
      and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR)
      was performed. The species identified were Mycobacterium abscessus subsp.
      bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium fortuitum
      (n = 3), Mycobacterium marseillense (n = 2), and Mycobacterium timonense (n = 1).
      Most of the isolates presented resistance to five or more of the antimicrobials
      tested. Typing profiles were mainly patient specific. The PFGE profiles indicated
      the presence of two clonal groups for M. abscessus subsp. abscessus and five
      clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in
      two patients. Given the observed multidrug resistance patterns and the
      possibility of transmission between patients, we suggest the implementation of
      continuous and routine investigation of NTM infection or colonization in CF
      patients, including countries with a high burden of tuberculosis disease. 

PMID- 24920767
TI  - Time between collection and storage significantly influences bacterial sequence
      composition in sputum samples from cystic fibrosis respiratory infections.
AB  - Spontaneously expectorated sputum is traditionally used as the sampling method
      for the investigation of lower airway infections. While guidelines exist for the
      handling of these samples for culture-based diagnostic microbiology, there is no
      comparable consensus on their handling prior to culture-independent analysis. The
      increasing incorporation of culture-independent approaches in diagnostic
      microbiology means that it is of critical importance to assess potential biases.
      The aim of this study was to assess the impact of delayed freezing on culture
      independent microbiological analyses and to identify acceptable parameters for
      sample handling. Sputum samples from eight adult cystic fibrosis (CF) patients
      were collected and aliquoted into sterile Bijou bottles. Aliquots were stored at
      room temperature before being frozen at -80  degrees C for increasing intervals,
      up to a 72-h period. Samples were treated with propidium monoazide to distinguish
      live from dead cells prior to DNA extraction, and 16S rRNA gene pyrosequencing
      was used to characterize their bacterial compositions. Substantial variation was
      observed in samples with high-diversity bacterial communities over time, whereas
      little variation was observed in low-diversity communities dominated by
      recognized CF pathogens, regardless of time to freezing. Partitioning into common
      and rare species demonstrated that the rare species drove changes in similarity.
      The percentage abundance of anaerobes over the study significantly decreased
      after 12 h at room temperature (P = 0.008). Failure to stabilize samples at -80 
      degrees C within 12 h of collection results in significant changes in the
      detected community composition.

PMID- 24920768
TI  - Assessment of ambiguous base calls in HIV-1 pol population sequences as a
      biomarker for identification of recent infections in HIV-1 incidence studies.
AB  - An increase in the proportion of ambiguous base calls in HIV-1 pol population
      sequences during the course of infection has been demonstrated in different study
      populations, and sequence ambiguity thresholds to classify infections as recent
      or nonrecent have been suggested. The aim of our study was to evaluate sequence
      ambiguities as a candidate biomarker for use in an HIV-1 incidence assay using
      samples from antiretroviral treatment-naive seroconverters with known durations
      of infection (German HIV-1 Seroconverter Study). We used 2,203 HIV-1 pol
      population sequences derived from 1,334 seroconverters to assess the sequence
      ambiguity method (SAM). We then compared the serological incidence BED capture
      enzyme immunoassay (BED-CEIA) with the SAM for a subset of 723 samples from 495
      seroconverters and evaluated a multianalyte algorithm that includes BED-CEIA
      results, SAM results, viral loads, and CD4 cell counts for 453 samples from 325
      seroconverters. We observed a significant increase in the proportion of sequence
      ambiguities with the duration of infection. A sequence ambiguity threshold of
      0.5% best identified recent infections with 76.7% accuracy. The mean duration of
      recency was determined to be 208 (95% confidence interval, 196 to 221) days. In
      the subset analysis, BED-CEIA achieved a significantly higher accuracy than the
      SAM (84.6 versus 75.5%, P < 0.001) and results were concordant for 64.2%
      (464/723) of the samples. Also, the multianalyte algorithm did not show better
      accuracy than the BED-CEIA (83.4 versus 84.3%, P = 0.786). In conclusion, the SAM
      and the multianalyte algorithm including SAM were inferior to the BED-CEIA, and
      the proportion of sequence ambiguities is therefore not a preferable biomarker
      for HIV-1 incidence testing. 

PMID- 24920769
TI  - Planctomycetes DNA in febrile aplastic patients with leukemia, rash, diarrhea,
      and micronodular pneumonia.
AB  - We found Planctomycetes DNA in 2 out of 100 blood samples from patients suffering
      from leukemia with neutropenia induced by chemotherapy, as well as fever, rash,
      pneumonia, and diarrhea. Antibiotic-resisting Planctomycetes may be pathogenic in
      these patients. 

PMID- 24920770
TI  - Hypertrophic adenoid is a major infection site of human bocavirus 1.
AB  - Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide,
      mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can
      persist for long periods of time in humans, probably through maintaining
      concatemers of the virus single-stranded DNA genome in the nuclei of infected
      cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine
      tonsils samples from patients with chronic adenotonsillar diseases, but nothing
      is known about the virus replication levels in those tissues. A 3-year
      prospective hospital-based study was conducted to detect and quantify HBoV1 DNA
      and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal
      secretions (NPS), and peripheral blood (PB) from patients undergoing
      tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was
      detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS,
      and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were
      higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in
      this tissue. High viral loads and detectable mRNA in the AD were associated with
      HBoV1 detection in the other sample sites. The adenoids are an important site of
      HBoV1 replication and persistence in children with tonsillar hypertrophy. The
      adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and
      this is associated with the detection of HBoV1 in secretions. 

PMID- 24920771
TI  - New sensitive one-step real-time duplex PCR method for group A and B HIV-2 RNA
      load.
AB  - The Agence Nationale de Recherche sur le Sida et les hepatites virales (ANRS)
      previously developed a widely used method for HIV-1 RNA quantification
      (Biocentric). Here, we report the development of a new specific and sensitive
      method for HIV-2 RNA quantification, based on an adaptation of the existing HIV-1
      protocol. The new test is based on TaqMan one-step reverse transcription
      quantitative PCR (qRT-PCR) targeting two conserved consensus regions of HIV-2
      (long terminal repeat [LTR] and gag). Analytic performances were determined in
      three laboratories. Clinical performances were evaluated on 100 plasma samples
      from HIV-2-infected patients (groups A, B, and H) by comparison with the assay
      currently used for the ANRS HIV-2 cohort. The specificity was 100%. Sensitivity
      was 50 copies/ml (cp/ml) and was optimized to 10 cp/ml. The within-run
      coefficients of variation in the three laboratories varied from 0.54% to 1.61% at
      4 log10 copies/ml and from 7.24% to 14.32% at 2 log10 cp/ml. The between-run
      coefficients of variation varied from 2.28% to 6.43%. Of the 39 clinical samples
      below 2 log10 in the current assay, the new test improved the detection or
      quantification of 17 samples, including eight group B samples. For quantifiable
      samples, similar loads were obtained with the two assays for group A samples. The
      median difference between the two assays for group B samples was +0.18 but with
      greater heterogeneity than for group A. The HIV-2 group H sample had similar
      results with the two assays. This new assay is highly sensitive and accurately
      quantifies the most prevalent HIV-2 groups. This test will be useful for
      monitoring low viral loads in HIV-2-infected patients. 

PMID- 24920772
TI  - Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal
      ulcer-associated Helicobacter pylori strains: a matched case-control study.
AB  - The Helicobacter pylori virulence gene, cagA, and active forms of the vacuolating
      cytotoxin gene, vacA, are major determinants of pathogenesis. However, previous
      studies linking these factors to disease risk have often included patients using
      aspirin/nonsteroidal anti-inflammatory agents (NSAIDs) or acid-suppressing drugs,
      both of which may confound results. Also, particularly for gastric cancer (GC),
      controls have often been of quite different ages. Here, we performed a careful
      study in a "clean" Belgian population with gastric cancer cases age and sex
      matched to 4 controls and with a parallel duodenal ulcer (DU) group. As in other
      populations, there was a close association between the presence of cagA and the
      vacA s1 genotype. For GC, associations were found for vacA s1-positive (P = 0.01,
      odds ratio [OR], 9.37; 95% confidence interval [CI], 1.16 to 201.89), i1-positive
      (P = 0.003; OR, 12.08; 95% CI, 1.50 to 259.64), and cagA-positive status (P <
      0.05; OR, infinity; 95% CI, 0.76 to infinity). For DU, associations were found
      with vacA s1 (P = 0.002; OR, 6.04; 95% CI, 1.52 to 27.87) and i1 (P = 0.004; OR,
      4.35; 95% CI, 1.36 to 14.78) status but not with cagA status. Neither condition
      showed independent associations with the vacA m1 allele or with more biologically
      active forms of cagA with longer 3' variable regions. In this Belgian population,
      the best markers of gastric cancer- and duodenal ulcer-associated strains are the
      vacA s1 and i1 genotypes. This fits with experimental data showing that the s and
      i regions are the key determinants of vacuolating cytotoxin activity. 

PMID- 24920773
TI  - Penicillin-susceptible group B streptococcal clinical isolates with reduced
      cephalosporin susceptibility.
AB  - We characterized penicillin-susceptible group B streptococcal (PSGBS) clinical
      isolates exhibiting no growth inhibition zone around a ceftibuten disk (CTB(r)
      PSGBS). The CTB(r) PSGBS isolates, for which augmented MICs of cefaclor and
      ceftizoxime were found, shared a T394A substitution in penicillin-binding protein
      2X (PBP 2X) and a T567I substitution in PBP 2B, together with an additional G429S
      substitution in PBP 2X or a T145A substitution in PBP 1A, although the T145A
      substitution in the transglycosidase domain of PBP 1A would have no effect on the
      level of resistance to ceftibuten.

PMID- 24920774
TI  - Prostatitis, steatitis, and diarrhea in a dog following presumptive flea-borne
      transmission of Bartonella henselae.
AB  - Bartonella henselae is increasingly associated with a variety of pathological
      entities, which are often similar in dogs and human patients. Following an acute
      flea infestation, a dog developed an unusual clinical presentation for canine
      bartonellosis. Comprehensive medical, microbiological, and surgical interventions
      were required for diagnosis and to achieve a full recovery. 

PMID- 24920775
TI  - Aerial prevalence of Aspergillus calidoustus isolates in and around a tertiary
      care hospital in Kuwait and assessment of their pathogenicity.
AB  - Seven Aspergillus calidoustus isolates from 486 Aspergillus spp. isolates (1.4%
      overall prevalence) from outdoor/indoor air samples and one isolate from the
      bronchoalveolar lavage fluid of a patient with pneumonia were obtained. These 8
      isolates exhibited reduced susceptibility to triazoles. Preliminary pathogenicity
      data from BALB/c mice suggest that A. calidoustus can persist in tissues for long
      periods without causing mortality. Further studies using graded doses of inoculum
      and immunosuppression models are warranted to gain an understanding of the
      factors associated with its pathogenicity and virulence. 

PMID- 24920777
TI  - Quality control MIC ranges used for telavancin with application of a revised CLSI
      reference broth microdilution method.
AB  - The telavancin broth microdilution susceptibility testing method was revised,
      which provides MIC results lower than those obtained by the previous method. This
      study was performed to reestablish the quality control ranges for telavancin when
      tested against the strains (updated MIC range) Staphylococcus aureus ATCC 29213
      (0.03 to 0.12 MUg/ml), Enterococcus faecalis ATCC 29212 (0.03 to 0.12 MUg/ml),
      and Streptococcus pneumoniae ATCC 49619 (0.004 to 0.015 MUg/ml).

PMID- 24920776
TI  - Epidemic diffusion of OXA-23-producing Acinetobacter baumannii isolates in Italy:
      results of the first cross-sectional countrywide survey.
AB  - Carbapenem-resistant Acinetobacter baumannii (CRAb) is emerging worldwide as a
      public health problem in various settings. The aim of this study was to
      investigate the prevalence of CRAb isolates in Italy and to characterize their
      resistance mechanisms and genetic relatedness. A countrywide cross-sectional
      survey was carried out at 25 centers in mid-2011. CRAb isolates were reported
      from all participating centers, with overall proportions of 45.7% and 22.2% among
      consecutive nonreplicate clinical isolates of A. baumannii from inpatients (n =
      508) and outpatients (n = 63), respectively. Most of them were resistant to
      multiple antibiotics, whereas all remained susceptible to colistin, with MIC50
      and MIC90 values of <= 0.5 mg/liter. The genes coding for carbapenemase
      production were identified by PCR and sequencing. OXA-23 enzymes (found in all
      centers) were by far the most common carbapenemases (81.7%), followed by OXA-58
      oxacillinases (4.5%), which were found in 7 of the 25 centers. In 6 cases, CRAb
      isolates carried both bla(OXA-23-like) and bla(OXA-58-like) genes. A repetitive
      extragenic palindromic (REP)-PCR technique, multiplex PCRs for group
      identification, and multilocus sequence typing (MLST) were used to determine the
      genetic relationships among representative isolates (n = 55). Two different
      clonal lineages were identified, including a dominant clone of sequence type 2
      (ST2) related to the international clone II (sequence group 1 [SG1], SG4, and
      SG5) and a clone of ST78 (SG6) previously described in Italy. Overall, our
      results demonstrate that OXA-23 enzymes have become the most prevalent
      carbapenemases and are now endemic in Italy. In addition, molecular typing
      profiles showed the presence of international and national clonal lineages in
      Italy.

PMID- 24920778
TI  - Biographical feature: John Matsen, M.D.

PMID- 24920779
TI  - When does 2 plus 2 equal 5? A review of antimicrobial synergy testing.
AB  - In this age of emerging antibiotic resistance, limited therapeutic options exist
      for treating multidrug-resistant organisms. Combination therapy is commonly
      employed to manage these infections despite little laboratory guidance as to the
      efficacy of this approach. Synergy testing methods have been used to assess the
      interaction of antibiotic combinations in vitro. This review will discuss the
      four primary methods used to assess synergy, as well as the data that exist for
      testing of cystic fibrosis. In the final analysis, this review concludes that
      there is not enough evidence to endorse synergy testing for routine clinical use.

PMID- 24920780
TI  - Accidental exposure to Burkholderia pseudomallei in the laboratory in the era of
      matrix-assisted laser desorption ionization-time of flight mass spectrometry.

PMID- 24920781
TI  - Novel strategy for typing Mycoplasma pneumoniae isolates by use of matrix
      assisted laser desorption ionization-time of flight mass spectrometry coupled
      with ClinProTools.
AB  - The typing of Mycoplasma pneumoniae mainly relies on the detection of nucleic
      acid, which is limited by the use of a single gene target, complex operation
      procedures, and a lengthy assay time. Here, matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS) coupled to
      ClinProTools was used to discover MALDI-TOF MS biomarker peaks and to generate a
      classification model based on a genetic algorithm (GA) to differentiate between
      type 1 and type 2 M. pneumoniae isolates. Twenty-five M. pneumoniae strains were
      used to construct an analysis model, and 43 Mycoplasma strains were used for
      validation. For the GA typing model, the cross-validation values, which reflect
      the ability of the model to handle variability among the test spectra and the
      recognition capability value, which reflects the model's ability to correctly
      identify its component spectra, were all 100%. This model contained 7 biomarker
      peaks (m/z 3,318.8, 3,215.0, 5,091.8, 5,766.8, 6,337.1, 6,431.1, and 6,979.9)
      used to correctly identify 31 type 1 and 7 type 2 M. pneumoniae isolates from 43
      Mycoplasma strains with a sensitivity and specificity of 100%. The strain
      distribution map and principle component analysis based on the GA classification
      model also clearly showed that the type 1 and type 2 M. pneumoniae isolates can
      be divided into two categories based on their peptide mass fingerprints. With the
      obvious advantages of being rapid, highly accurate, and highly sensitive and
      having a low cost and high throughput, MALDI-TOF MS ClinProTools is a powerful
      and reliable tool for M. pneumoniae typing. 

PMID- 24920782
TI  - Interlaboratory comparison of sample preparation methods, database expansions,
      and cutoff values for identification of yeasts by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry using a yeast test panel.
AB  - An interlaboratory study using matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF MS) to determine the identification of
      clinically important yeasts (n = 35) was performed at 11 clinical centers, one
      company, and one reference center using the Bruker Daltonics MALDI Biotyper
      system. The optimal cutoff for the MALDI-TOF MS score was investigated using
      receiver operating characteristic (ROC) curve analyses. The percentages of
      correct identifications were compared for different sample preparation methods
      and different databases. Logistic regression analysis was performed to analyze
      the association between the number of spectra in the database and the percentage
      of strains that were correctly identified. A total of 5,460 MALDI-TOF MS results
      were obtained. Using all results, the area under the ROC curve was 0.95 (95%
      confidence interval [CI], 0.94 to 0.96). With a sensitivity of 0.84 and a
      specificity of 0.97, a cutoff value of 1.7 was considered optimal. The overall
      percentage of correct identifications (formic acid-ethanol extraction method,
      score >= 1.7) was 61.5% when the commercial Bruker Daltonics database (BDAL) was
      used, and it increased to 86.8% by using an extended BDAL supplemented with a
      Centraalbureau voor Schimmelcultures (CBS)-KNAW Fungal Biodiversity Centre in
      house database (BDAL+CBS in-house). A greater number of main spectra (MSP) in the
      database was associated with a higher percentage of correct identifications (odds
      ratio [OR], 1.10; 95% CI, 1.05 to 1.15; P < 0.01). The results from the direct
      transfer method ranged from 0% to 82.9% correct identifications, with the results
      of the top four centers ranging from 71.4% to 82.9% correct identifications. This
      study supports the use of a cutoff value of 1.7 for the identification of yeasts
      using MALDI-TOF MS. The inclusion of enough isolates of the same species in the
      database can enhance the proportion of correctly identified strains. Further
      optimization of the preparation methods, especially of the direct transfer
      method, may contribute to improved diagnosis of yeast-related infections. 

PMID- 24920783
TI  - PCR-based detection and molecular characterization of shiga toxin-producing
      Escherichia coli strains in a routine microbiology laboratory over 16 years.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a heterogeneous group of
      bacteria causing disease ranging from asymptomatic carriage and mild infection to
      hemolytic uremic syndrome (HUS). Here, we describe patients with STEC infection
      and characterize the STEC strains detected in our laboratory by use of PCR for
      stx1, stx2, and eae from 1996 through 2011. Patient information was collected
      from referral forms and from the Norwegian Surveillance System for Communicable
      Diseases. STEC isolates were characterized with respect to serogroup or serotype,
      selected potential virulence genes, and multilocus variable-number tandem-repeat
      analysis (MLVA) genotype. STEC strains were isolated from 138 (1.09%) of 12,651
      patients tested. STEC strains of serogroups O26, O103, O121, O145, and O157 were
      the most frequent. These serogroups, except non-sorbitol-fermenting O157, were
      also the most frequent among the 11 patients (all <=5 years old) who developed
      HUS. Twenty-four STEC strains were classified as being HUS associated based on an
      epidemiological link to a HUS case, including an MLVA genotype identical to that
      of the STEC strain. The age of the patient (<=5 years) and the genes eae and
      stx2a were significantly associated with HUS-associated STEC (P < 0.05 for each
      parameter), while stx1 was associated with non-HUS-associated STEC (P < 0.05).
      All of the potential virulence genes analyzed, except ehxA, were significantly
      more frequent among HUS-associated than non-HUS-associated strains (P < 0.05 for
      each gene). However, these genes were also present in some non-HUS-associated
      STEC strains and could therefore not reliably differentiate between HUS
      associated and non-HUS-associated STEC strains. 

PMID- 24920784
TI  - Age at menarche and risks of all-cause and cardiovascular death: a systematic
      review and meta-analysis.
AB  - We conducted a systematic review and meta-analysis to investigate the
      associations between menarcheal age and all-cause and cardiovascular death.
      Medline, Embase, Scopus, and Web of Knowledge were searched for articles
      published prior to March 2013 reporting on the associations between menarcheal
      age and death from all causes or from cardiovascular disease (total
      cardiovascular disease, ischemic heart disease (IHD), and stroke) in adult women.
      Nine articles were eligible for inclusion; these reported 5 estimates each for
      death from all causes and total cardiovascular death, 6 estimates for IHD, and 7
      estimates for death from stroke. Our meta-analysis showed that each 1-year
      increase in age at menarche was associated with a 3% lower relative risk of death
      from all causes (pooled hazard ratio = 0.97, 95% confidence interval: 0.96, 0.98)
      with low heterogeneity (I(2) = 32.2%). Meta-analysis of 2 cohorts showed a higher
      risk of death from all causes for women who experienced early menarche (at <12
      years of age) versus "not early" menarche (at >= 12 years of age) (pooled hazard
      ratio = 1.23, 95% confidence interval: 1.10, 1.38; I(2) = 0%). An inverse
      association between age at menarche and death from IHD was observed only among
      nonsmoking populations or populations with low prevalence of smoking. We found no
      evidence of association between age at menarche and death from all cardiovascular
      diseases or stroke. Early menarche was consistently associated with higher risk
      of death from all causes. Further studies are needed to clarify the role of
      menarcheal age on cardiovascular outcomes and to investigate the potential
      modifying role of smoking.

PMID- 24920785
TI  - Snippets from the past: cohort analysis of disease rates-another piece in a
      seemingly still incomplete puzzle.
AB  - For almost a century, epidemiologists have stratified age-specific disease rates
      by year of birth to better understand the distribution of a disease in a
      population and its evolution across time. In the present article, I review the
      contributions of John Brownlee, Kristian Feyer Andvord, and Wade Hampton Frost
      and, to accentuate the similarities of their approaches, redraw their original
      graphs of age-specific death rates of tuberculosis organized either by year of
      death or year of birth. In addition, this article reports on an apparently
      universally forgotten publication in the American Journal of Hygiene published in
      1929, which both upsets the conventional history of the earliest reports of
      disease rates stratified by birth cohorts and challenges the theory that Frost
      discovered cohort analysis independently and gave it its name. 

PMID- 24920786
TI  - Reduced risk of lung cancer with metformin therapy in diabetic patients: a
      systematic review and meta-analysis.
AB  - Emerging evidence from epidemiologic studies and basic science suggests an
      inverse association between metformin use and cancer risk in diabetic patients.
      However, the association with lung cancer is not consistent. We summarized the
      evidence currently available (2009-2013) and explored sources of heterogeneity.
      Metformin therapy was associated with significantly lower risks of cancers of the
      lung (4 studies; pooled relative risk = 0.71, 95% confidence interval (CI): 0.55,
      0.95; P = 0.02) and respiratory system (6 studies; pooled relative risk = 0.85,
      95% CI: 0.75, 0.96; P = 0.01). There was evidence of moderate heterogeneity (I(2)
      > 50%). The major sources of heterogeneity were smoking adjustment status and
      cancer site. The relative risk from studies that adjusted for smoking was 1.16
      fold (95% CI: 1.00, 1.35) closer to the null than that from studies not adjusting
      for smoking. The relative risk of respiratory cancer was 1.23-fold (95% CI: 1.02,
      1.49) closer to the null than that for lung cancer. In conclusion, metformin use
      appears to be associated with lower risks of lung and respiratory cancer in
      diabetic patients. However, caution regarding overestimation is needed, since
      adjustment for smoking attenuates the association. 

PMID- 24920787
TI  - 'The dilemmas of breast cancer treatment and increased fracture risk' by Malik.

PMID- 24920788
TI  - The dilemmas of breast cancer treatment and increased fracture risk.

PMID- 24920789
TI  - Early-stage lung cancer--what do the experts recommend?

PMID- 24920790
TI  - Phase III trial of concurrent thoracic radiotherapy with either first- or third
      cycle chemotherapy for limited-disease small-cell lung cancer.

PMID- 24920791
TI  - Molecular mechanism of the airborne transmissibility of H9N2 avian influenza A
      viruses in chickens.
AB  - H9N2 avian influenza virus has been prevalent in poultry in many parts of the
      world since the 1990s and occasionally crosses the host barrier, transmitting to
      mammals, including humans. In recent years, these viruses have contributed genes
      to H5N1 and H7N9 influenza viruses, threatening public health. To explore the
      molecular mechanism for the airborne transmission of H9N2 virus, we compared two
      genetically close strains isolated from chickens in 2001,
      A/chicken/Shanghai/7/2001(SH7) and A/chicken/Shanghai/14/2001 (SH14). SH7 is
      airborne transmissible between chickens, whereas SH14 is not. We used reverse
      genetics and gene swapping to derive recombinant SH7 (rSH7), rSH14, and a panel
      of reassortant viruses. Among the reassortant viruses, we identified segments HA
      and PA as governing the airborne transmission among chickens. In addition, the NP
      and NS genes also contributed to a lesser extent. Furthermore, the mutational
      analyses showed the transmissibility phenotype predominantly mapped to the HA and
      PA genes, with HA-K363 and PA-L672 being important for airborne transmissibility
      among chickens. In addition, the viral infectivity and acid stability are related
      to the airborne transmissibility. Importantly, airborne transmission studies of
      18 arbitrarily chosen H9N2 viruses from our collections confirmed the importance
      of both 363K in HA and 672L in PA in determining their levels of
      transmissibility. Our finding elucidates the genetic contributions to H9N2
      transmissibility in chickens and highlights the importance of their prevalence in
      poultry. IMPORTANCE: Our study investigates the airborne transmissibility of H9N2
      viruses in chickens and the subsequent epidemic. H9N2 virus is the donor for
      several prevalent reassortant influenza viruses, such as H7N9/2013 and the H5N1
      viruses. Poultry as the reservoir hosts of influenza virus is closely associated
      with human society. Airborne transmission is an efficient pathway for influenza
      virus transmission among flocks and individuals. Exploring the mechanism of the
      airborne transmission of the H9N2 virus in chickens could provide essential data
      regarding prevention and control of influenza endemics and pandemics.

PMID- 24920792
TI  - Poly(I:C) treatment leads to interferon-dependent clearance of hepatitis B virus
      in a hydrodynamic injection mouse model.
AB  - We have previously shown that poly(I:C) activates murine hepatic cells to produce
      interferon (IFN) and suppresses hepatitis B virus (HBV) replication in vitro.
      Therefore, we addressed whether poly(I:C) is able to induce the clearance of HBV
      in vivo. The chronic HBV replication mouse model was established by the
      hydrodynamic injection (HI) of pAAV-HBV1.2 into the tail veins of wild-type and
      IFN-alpha/betaR-, IFN-gamma-, and CXCR3-deficient C57BL/6 mice. Fourteen days
      post-HI of pAAV-HBV1.2, mice were administered poly(I:C) by intraperitoneal
      injection, intramuscular injection, or HI. Only treatment of poly(I:C) by HI led
      to HBV clearance in wild-type C57BL/6 mice. Serum HBsAg disappeared within 40
      days postinfection (dpi) in mice that received poly(I:C) by HI, and this was
      accompanied by the appearance of anti-HBs antibodies. HBV-specific T-cell and
      antibody responses were significantly enhanced by HI of poly(I:C). HBV
      replication intermediates and HBcAg-positive hepatocytes were eliminated in the
      liver. HI of poly(I:C) induced the production of IFNs in mice and enhanced the
      levels of cytokines, IFN-stimulated genes, and T-cell markers in the liver.
      Importantly, poly(I:C)-induced HBV clearance was impaired in IFN-alpha/betaR-,
      IFN-gamma-, and CXCR3-deficient mice, indicating that the induction of type I IFN
      and the stimulation and recruitment of T cells into the liver are essential for
      HBV clearance in this model. Taken together, the application of poly(I:C) by HI
      into the liver enhances innate and adaptive immune responses and leads to HBV
      clearance in an HBV mouse model, implicating the potential of intrahepatic Toll
      like receptor 3 (TLR3) activation for the treatment of chronic hepatitis B
      patients. IMPORTANCE: It has become well accepted that immunomodulation is a
      potentially useful approach to treat chronic viral infection. Recently,
      combinations of antiviral treatment and therapeutic vaccinations were evaluated
      for therapies of chronic hepatitis B virus (HBV) infection. Activation of the
      innate immune branch may also be important for viral control and contributes to
      HBV clearance. Our present study demonstrated that hepatic TLR3 activation led to
      clearance of hepatitis B virus in an HBV mouse model. For the first time, we
      showed that HBV clearance in this model is dependent not only on type I
      interferon (IFN) but also on type II IFN, indicating a coordinated action of
      innate and adaptive immune responses. T-cell recruitment appeared to be critical
      for the success of TLR3-mediated antiviral action. These findings implicate the
      potential of intrahepatic TLR3 activation for the treatment of chronic HBV
      infection.

PMID- 24920793
TI  - Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral
      immunity-mediated broad protection against influenza in mice.
AB  - Influenza vaccines aimed at inducing antibody (Ab) responses against viral
      surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to
      infection with the same subtypes. Vaccines targeting viral conserved determinants
      shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a
      broad protection against different subtypes. We proposed that vaccines targeting
      both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide
      protection against infection with the same subtype and also HSI against other
      subtypes. We report here that single intranasal immunization with a recombinant
      adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced
      significant HA- and M2e-specific Ab responses, along with protection against
      heterosubtypic challenge in mice. The protection is superior compared to that
      induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While
      protection against homotypic H5 virus is primarily mediated by virus-neutralizing
      Abs, the cross-protection is associated with Abs directed to conserved stalk HA
      and M2e that seem to have an additive effect. Consistently, adoptive transfer of
      antisera induced by rAdH5/M2e provided the best protection against heterosubtypic
      challenge compared to that provided by antisera derived from mice immunized with
      rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines
      encoding both H5 and M2e as universal vaccines against different IAV subtypes.
      IMPORTANCE: Current licensed influenza vaccines provide protection limited to the
      infection with same virus strains; therefore, the composition of influenza
      vaccines has to be revised every year. We have developed a new universal
      influenza vaccine that is highly efficient in induction of long-lasting cross
      protection against different influenza virus strains. The cross-protection is
      associated with a high level of vaccine-induced antibodies against the conserved
      stalk domain of influenza virus hemagglutinin and the ectodomain of matrix
      protein. The vaccine could be used to stimulate cross-protective antibodies for
      the prevention and treatment of influenza with immediate effect for individuals
      who fail to respond to or receive the vaccine in due time. The vaccine offers a
      new tool to control influenza outbreaks, including pandemics.

PMID- 24920794
TI  - Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on
      susceptibility to integrase strand transfer inhibitors.
AB  - Studies on the in vitro susceptibility of SIV to integrase strand transfer
      inhibitors (INSTIs) have been rare. In order to determine the susceptibility of
      SIVmac239 to INSTIs and characterize the genetic pathways that might lead to drug
      resistance, we inserted various integrase (IN) mutations that had been selected
      with HIV under drug pressure with raltegravir (RAL), elvitegravir (EVG), and
      dolutegravir (DTG) into the IN gene of SIV. We evaluated the effects of these
      mutations on SIV susceptibility to INSTIs and on viral infectivity. Sequence
      alignments of SIVmac239 IN with various HIV-1 isolates showed a high degree of
      homology and conservation of each of the catalytic triad and the key residues
      involved in drug resistance. Each of the G118R, Y143R, Q148R, R263K, and
      G140S/Q148R mutations, when introduced into SIV, impaired infectiousness and
      replication fitness compared to wild-type virus. Using TZM-bl cells, we
      demonstrated that the Q148R and N155H mutational pathways conferred resistance to
      EVG (36- and 62-fold, respectively), whereas R263K also displayed moderate
      resistance to EVG (12-fold). In contrast, Y143R, Q148R, and N155H all yielded low
      levels of resistance to RAL. The combination of G140S/Q148R conferred high-level
      resistance to both RAL and EVG (>300- and 286-fold, respectively). DTG remained
      fully effective against all site-directed mutants except G118R and R263K. Thus,
      HIV INSTI mutations, when inserted into SIV, resulted in a similar phenotype.
      These findings suggest that SIV and HIV may share similar resistance pathways
      profiles and that SIVmac239 could be a useful nonhuman primate model for studies
      of HIV resistance to INSTIs. IMPORTANCE: The goal of our project was to establish
      whether drug resistance against integrase inhibitors in SIV are likely to be the
      same as those responsible for drug resistance in HIV. Our data answer this
      question in the affirmative and show that SIV can probably serve as a good animal
      model for studies of INSTIs and as an early indicator for possible emergent
      mutations that may cause treatment failure. An SIV-primate model remains an
      invaluable tool for investigating questions related to the potential role of
      INSTIs in HIV therapy, transmission, and pathogenesis, and the present study will
      facilitate each of the above.

PMID- 24920795
TI  - Impaired immune response to vaccination against infection with human respiratory
      syncytial virus at advanced age.
AB  - Elderly humans are prone to severe infection with human respiratory syncytial
      virus (HRSV). The aging of today's human population warrants the development of
      protective vaccination strategies aimed specifically at the elderly. This may
      require special approaches due to deteriorating immune function. To design and
      test vaccination strategies tailored to the elderly population, we need to
      understand the host response to HRSV vaccination and infection at old age.
      Moreover, the preclinical need for testing of candidate vaccines requires
      translational models resembling susceptibility to the (unadapted) human pathogen.
      Here, we explored the effects of aging on immunity and protection induced by a
      model HRSV vaccine candidate in a translational aging model in cotton rats
      (Sigmodon hispidus) and examined possibilities to optimize vaccination concepts
      for the elderly. We immunized young and aged cotton rats with a live-attenuated
      recombinant HRSV vaccine candidate and analyzed the induced immune response to
      and protection against challenge with HRSV. In old cotton rats, HRSV infection
      persisted longer, and vaccination induced less protection against infection. Aged
      animals developed lower levels of vaccine-induced IgG, virus-neutralizing serum
      antibodies, and IgA in lungs. Moreover, booster responses to HRSV challenge were
      impaired in animals vaccinated at an older age. However, increased dose and
      reduced attenuation of vaccine improved protection even in old animals. This
      study shows that cotton rats provide a model for studying the effects of aging on
      the immune response to the human respiratory pathogen HRSV and possibilities to
      optimize vaccine concepts for the elderly. IMPORTANCE: HRSV infection poses a
      risk for severe disease in the elderly. The aging of the population warrants
      increased efforts to prevent disease at old age, whereas HRSV vaccines are only
      in the developmental phase. The preclinical need for testing of candidate human
      vaccines requires translational models resembling susceptibility to the natural
      human virus. Moreover, we need to gain insight into waning immunity at old age,
      as this is a special concern in vaccine development. In this study, we explored
      the effect of age on protection and immunity against an experimental HRSV vaccine
      in aged cotton rats (Sigmodon hispidus), a rodent species that provides a model
      representing natural susceptibility to human viruses. Older animals generate
      fewer antibodies upon vaccination and require a higher vaccine dose for
      protection. Notably, during the early secondary immune response to subsequent
      HRSV infection, older animals showed less protection and a slower increase of the
      virus-neutralizing antibody titer.

PMID- 24920796
TI  - Locking and blocking the viral landscape of an alphavirus with neutralizing
      antibodies.
AB  - Alphaviruses are serious, sometimes lethal human pathogens that belong to the
      family Togaviridae. The structures of human Venezuelan equine encephalitis virus
      (VEEV), an alphavirus, in complex with two strongly neutralizing antibody Fab
      fragments (F5 and 3B4C-4) have been determined using a combination of cryo
      electron microscopy and homology modeling. We characterize these monoclonal
      antibody Fab fragments, which are known to abrogate VEEV infectivity by binding
      to the E2 (envelope) surface glycoprotein. Both of these antibody Fab fragments
      cross-link the surface E2 glycoproteins and therefore probably inhibit
      infectivity by blocking the conformational changes that are required for making
      the virus fusogenic. The F5 Fab fragment cross-links E2 proteins within one
      trimeric spike, whereas the 3B4C-4 Fab fragment cross-links E2 proteins from
      neighboring spikes. Furthermore, F5 probably blocks the receptor-binding site,
      whereas 3B4C-4 sterically hinders the exposure of the fusion loop at the end of
      the E2 B-domain. IMPORTANCE: Alphaviral infections are transmitted mainly by
      mosquitoes. Venezuelan equine encephalitis virus (VEEV) is an alphavirus with a
      wide distribution across the globe. No effective vaccines exist for alphaviral
      infections. Therefore, a better understanding of VEEV and its associated
      neutralizing antibodies will help with the development of effective drugs and
      vaccines.

PMID- 24920797
TI  - Intranasal P particle vaccine provided partial cross-variant protection against
      human GII.4 norovirus diarrhea in gnotobiotic pigs.
AB  - Noroviruses (NoVs) are the leading cause of nonbacterial acute gastroenteritis
      worldwide in people of all ages. The P particle is a novel vaccine candidate
      derived from the protruding (P) domain of the NoV VP1 capsid protein. This study
      utilized the neonatal gnotobiotic pig model to evaluate the protective efficacies
      of primary infection, P particles, and virus-like particles (VLPs) against NoV
      infection and disease and the T cell responses to these treatments. Pigs either
      were vaccinated intranasally with GII.4/1997 NoV (VA387)-derived P particles or
      VLPs or were inoculated orally with a GII.4/2006b NoV variant. At postinoculation
      day (PID) 28, pigs either were euthanized or were challenged with the GII.4/2006b
      variant and monitored for diarrhea and virus shedding for 7 days. The T cell
      responses in intestinal and systemic lymphoid tissues were examined. Primary NoV
      infection provided 83% homologous protection against diarrhea and 49% homologous
      protection against virus shedding, while the P particle and VLP vaccines provided
      cross-variant protection (47% and 60%, respectively) against diarrhea. The
      protection rates against diarrhea are significantly inversely correlated with T
      cell expansion in the duodenum and are positively correlated with T cell
      expansion in the ileum and spleen. The P particle vaccine primed for stronger
      immune responses than VLPs, including significantly higher numbers of activated
      CD4+ T cells in all tissues, gamma interferon-producing (IFN-gamma+) CD8+ T cells
      in the duodenum, regulatory T cells (Tregs) in the blood, and transforming growth
      factor beta (TGF-beta)-producing CD4+ CD25- FoxP3+ Tregs in the spleen
      postchallenge, indicating that P particles are more immunogenic than VLPs at the
      same dose. In conclusion, the P particle vaccine is a promising vaccine candidate
      worthy of further development. IMPORTANCE: The norovirus (NoV) P particle is a
      vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid
      protein. P particles can be easily produced in Escherichia coli at high yields
      and thus may be more economically viable than the virus-like particle (VLP)
      vaccine. This study demonstrated, for the first time, the cross-variant
      protection (46.7%) of the intranasal P particle vaccine against human NoV
      diarrhea and revealed in detail the intestinal and systemic T cell responses by
      using the gnotobiotic pig model. The cross-variant protective efficacy of the P
      particle vaccine was comparable to that of the VLP vaccine in pigs (60%) and to
      the homologous protective efficacy of the VLP vaccine in humans (47%). NoV is now
      the leading cause of pediatric dehydrating diarrhea, responsible for
      approximately 1 million hospital visits for U.S. children and 218,000 deaths in
      developing countries. The P particle vaccine holds promise for reducing the
      disease burden and mortality.

PMID- 24920798
TI  - West nile virus-induced activation of mammalian target of rapamycin complex 1
      supports viral growth and viral protein expression.
AB  - Since its introduction in New York City, NY, in 1999, West Nile virus (WNV) has
      spread to all 48 contiguous states of the United States and is now the leading
      cause of epidemic encephalitis in North America. As a member of the family
      Flaviviridae, WNV is part of a group of clinically important human pathogens,
      including dengue virus and Japanese encephalitis virus. The members of this
      family of positive-sense, single-stranded RNA viruses have limited coding
      capacity and are therefore obligated to co-opt a significant amount of cellular
      factors to translate their genomes effectively. Our previous work has shown that
      WNV growth was independent of macroautophagy activation, but the role of the
      evolutionarily conserved mammalian target of rapamycin (mTOR) pathway during WNV
      infection was not well understood. mTOR is a serine/threonine kinase that acts as
      a central cellular censor of nutrient status and exercises control of vital
      anabolic and catabolic cellular responses such as protein synthesis and
      autophagy, respectively. We now show that WNV activates mTOR and cognate
      downstream activators of cap-dependent protein synthesis at early time points
      postinfection and that pharmacologic inhibition of mTOR (KU0063794) significantly
      reduced WNV growth. We used an inducible Raptor and Rictor knockout mouse
      embryonic fibroblast (MEF) system to further define the role of mTOR complexes 1
      and 2 in WNV growth and viral protein synthesis. Following inducible genetic
      knockout of the major mTOR cofactors raptor (TOR complex 1 [TORC1]) and rictor
      (TORC2), we now show that TORC1 supports flavivirus protein synthesis via cap
      dependent protein synthesis pathways and supports subsequent WNV growth.
      IMPORTANCE: Since its introduction in New York City, NY, in 1999, West Nile virus
      (WNV) has spread to all 48 contiguous states in the United States and is now the
      leading cause of epidemic encephalitis in North America. Currently, the mechanism
      by which flaviviruses such as WNV translate their genomes in host cells is
      incompletely understood. Elucidation of the host mechanisms required to support
      WNV genome translation will provide broad understanding for the basic mechanisms
      required to translate capped viral RNAs. We now show that WNV activates mTOR and
      cognate downstream activators of cap-dependent protein synthesis at early time
      points postinfection. Following inducible genetic knockout of the major mTOR
      complex cofactors raptor (TORC1) and rictor (TORC2), we now show that TORC1
      supports WNV growth and protein synthesis. This study demonstrates the
      requirement for TORC1 function in support of WNV RNA translation and provides
      insight into the mechanisms underlying flaviviral RNA translation in mammalian
      cells.

PMID- 24920800
TI  - Stabilizing the native trimer of HIV-1 Env by destabilizing the heterodimeric
      interface of the gp41 postfusion six-helix bundle.
AB  - The HIV-1 envelope glycoprotein (Env) is a trimer of gp120-gp41 heterodimers and
      is essential for viral entry. The gp41 subunit in native, prefusion trimeric Env
      exists in a metastable conformation and attains a stable six-helix bundle (6-HB)
      conformation comprised of a trimer of N-heptad repeat (NHR) and C-heptad repeat
      (CHR) heterodimers, that drives the fusion of viral and cellular membranes. We
      attempted to stabilize native Env trimers by incorporation of mutations at the
      NHR-CHR interface that disrupt the postfusion 6-HB of gp41. The mutations V570D
      and I573D stabilize native Env of the HIV-1 JRFL strain and occlude
      nonneutralizing epitopes to a greater extent than the previously identified I559P
      mutation that is at the interface of the NHR trimers in the 6-HB. The mutations
      prevent soluble-CD4 (sCD4)-induced gp120 shedding and 6-HB formation. In the
      context of cell surface-expressed JRFL Env, introduction of a previously reported
      additional disulfide between residues A501 and T605 perturbs the native
      conformation, though this effect is partially alleviated by furin coexpression.
      The data suggest that positions 570 and 573 are surface proximal in native Env
      and that the NHR homotrimeric coiled coil in native Env terminates before or
      close to residue 573. Aspartic acid substitutions at these positions stabilize
      native trimers through destabilization of the postfusion 6-HB conformation. These
      mutations can be used to stabilize Env in a DNA vaccine format. IMPORTANCE: The
      major protein on the surface of HIV-1 is the envelope (Env) glycoprotein. Env is
      a trimer of gp120-gp41 heterodimers. gp120 is involved in receptor/coreceptor
      binding and gp41 in the fusion of viral and cellular membranes. Like many other
      viral fusion proteins, the gp41 subunit in native trimeric Env exists in a
      metastable conformation. gp41 readily forms a stable six-helix bundle (6-HB)
      conformation comprised of a trimer of N-heptad repeat (NHR) and C-heptad repeat
      (CHR) heterodimers that drives fusion of viral and cellular membranes. While it
      is expected that native Env is a good immunogen, its metastability results in
      exposure of immunodominant nonneutralizing epitopes. In the present study, we
      stabilize native Env trimers by incorporation of a number of different mutations
      at the NHR-CHR interface that disrupt the postfusion 6-HB of gp41. The stabilized
      constructs described here can be incorporated into DNA vaccine candidates.

PMID- 24920799
TI  - The hop-like stress-induced protein 1 cochaperone is a novel cell-intrinsic
      restriction factor for mitochondrial tombusvirus replication.
AB  - Recent genome-wide screens reveal that the host cells express an arsenal of
      proteins that inhibit replication of plus-stranded RNA viruses by functioning as
      cell-intrinsic restriction factors of viral infections. One group of cell
      intrinsic restriction factors against tombusviruses contains tetratricopeptide
      repeat (TPR) domains that directly interact with the viral replication proteins.
      In this paper, we find that the TPR domain-containing Hop-like stress-inducible
      protein 1 (Sti1p) cochaperone selectively inhibits the mitochondrial membrane
      based replication of Carnation Italian ringspot tombusvirus (CIRV). In contrast,
      Sti1/Hop does not inhibit the peroxisome membrane-based replication of the
      closely related Tomato bushy stunt virus (TBSV) or Cucumber necrosis virus (CNV)
      in a yeast model or in plants. Deletion of STI1 in yeast leads to up to a 4-fold
      increase in CIRV replication, and knockdown of the orthologous Hop cochaperone in
      plants results in a 3-fold increase in CIRV accumulation. Overexpression of Sti1p
      derivatives in yeast reveals that the inhibitory function depends on the TPR1
      domain known to interact with heat shock protein 70 (Hsp70), but not on the TPR2
      domain interacting with Hsp90. In vitro CIRV replication studies based on
      isolated mitochondrial preparations and purified recombinant proteins has
      confirmed that Sti1p, similar to the TPR-containing Cyp40-like Cpr7p cyclophilin
      and the Ttc4 oncogene-like Cns1 cochaperone, is a strong inhibitor of CIRV
      replication. Sti1p interacts and colocalizes with the CIRV replication proteins
      in yeast. Our findings indicate that the TPR-containing Hop/Sti1 cochaperone
      could act as a cell-intrinsic virus restriction factor of the mitochondrial CIRV,
      but not against the peroxisomal tombusviruses in yeast and plants. IMPORTANCE:
      The host cells express various cell-intrinsic restriction factors that inhibit
      the replication of plus-stranded RNA viruses. In this paper, the authors find
      that the Hop-like stress-inducible protein 1 (Sti1p) cochaperone selectively
      inhibits the mitochondrial membrane-based replication of Carnation Italian
      ringspot tombusvirus (CIRV) in yeast. Deletion of STI1 in yeast or knockdown of
      the orthologous Hop cochaperone in plants leads to increased CIRV replication. In
      addition, overexpression of Sti1p derivatives in yeast reveals that the
      inhibitory function depends on the TPR1 domain known to interact with heat shock
      protein 70 (Hsp70), but not on the TPR2 domain interacting with Hsp90. In vitro
      CIRV replication studies based on isolated mitochondrial preparations and
      purified recombinant proteins have confirmed that Sti1p is a strong inhibitor of
      CIRV replication. The authors' findings reveal that the Hop/Sti1 cochaperone
      could act as a cell-intrinsic restriction factor against the mitochondrial CIRV,
      but not against the related peroxisomal tombusviruses.

PMID- 24920801
TI  - Limited type I interferons and plasmacytoid dendritic cells during neonatal
      respiratory syncytial virus infection permit immunopathogenesis upon reinfection.
AB  - Respiratory syncytial virus (RSV) infection is the number one cause of
      bronchiolitis in infants, yet no vaccines are available because of a lack of
      knowledge of the infant immune system. Using a neonatal mouse model, we
      previously revealed that mice initially infected with RSV as neonates develop Th2
      biased immunopathophysiologies during reinfection, and we demonstrated a role for
      enhanced interleukin-4 receptor alpha (IL-4Ralpha) expression on T helper cells
      in these responses. Here we show that RSV infection in neonates induced limited
      type I interferon (IFN) and plasmacytoid dendritic cell (pDC) responses. IFN
      alpha (IFN-alpha) treatment or adoptive transfer of adult pDCs capable of
      inducing IFN-alpha prior to neonatal RSV infection decreased Th2-biased
      immunopathogenesis during reinfection. A reduced viral load and downregulation of
      IL-4Ralpha on Th2 cells were observed in IFN-alpha-treated neonatal mice,
      suggesting dual mechanisms of action. IMPORTANCE: Respiratory syncytial virus
      (RSV) is the most significant cause of lower respiratory tract infection in
      infancy worldwide. Despite the dire need, we have failed to produce efficacious
      RSV vaccines or therapeutics. Part of the reason for this failure is our lack of
      understanding of how RSV interacts with the infant immune system to suppress the
      development of protective immunity. In the study described in the present paper,
      we used a neonatal mouse model, which more closely mimics human infants, to study
      the role of the innate immune system, particularly type I interferons (IFNs) and
      plasmacytoid dendritic cells (pDCs), in the pathogenesis of RSV infection. RSV
      infection in neonates induced limited type I IFN and pDC responses. IFN-alpha
      treatment or adoptive transfer of adult pDCs capable of producing IFN-alpha prior
      to neonatal RSV infection decreased Th2-biased immunopathogenesis during
      reinfection. These data suggest that IFN-alpha is a promising target for future
      RSV vaccine design.

PMID- 24920802
TI  - Rewiring of cellular membrane homeostasis by picornaviruses.
AB  - Viruses are obligatory intracellular parasites and utilize host elements to
      support key viral processes, including penetration of the plasma membrane,
      initiation of infection, replication, and suppression of the host's antiviral
      defenses. In this review, we focus on picornaviruses, a family of positive-strand
      RNA viruses, and discuss the mechanisms by which these viruses hijack the
      cellular machinery to form and operate membranous replication complexes. Studies
      aimed at revealing factors required for the establishment of viral replication
      structures identified several cellular-membrane-remodeling proteins and led to
      the development of models in which the virus used a preexisting cellular-membrane
      shaping pathway "as is" for generating its replication organelles. However, as
      more data accumulate, this view is being increasingly questioned, and it is
      becoming clearer that viruses may utilize cellular factors in ways that are
      distinct from the normal functions of these proteins in uninfected cells. In
      addition, the proteincentric view is being supplemented by important new studies
      showing a previously unappreciated deep remodeling of lipid homeostasis,
      including extreme changes to phospholipid biosynthesis and cholesterol
      trafficking. The data on viral modifications of lipid biosynthetic pathways are
      still rudimentary, but it appears once again that the viruses may rewire existing
      pathways to generate novel functions. Despite remarkable progress, our
      understanding of how a handful of viral proteins can completely overrun the
      multilayered, complex mechanisms that control the membrane organization of a
      eukaryotic cell remains very limited. 

PMID- 24920803
TI  - Human cytomegalovirus modulates monocyte-mediated innate immune responses during
      short-term experimental latency in vitro.
AB  - The ability of human cytomegalovirus (HCMV) to establish lifelong persistence and
      reactivate from latency is critical to its success as a pathogen. Here we
      describe a short-term in vitro model representing the events surrounding HCMV
      latency and reactivation in circulating peripheral blood monocytes that was
      developed in order to study the immunological consequence of latent virus
      carriage. Infection of human CD14(+) monocytes by HCMV resulted in the immediate
      establishment of latency, as evidenced by the absence of particular lytic gene
      expression, the transcription of latency-associated mRNAs, and the maintenance of
      viral genomes. Latent HCMV induced cellular differentiation to a macrophage
      lineage, causing production of selective proinflammatory cytokines and myeloid
      cell chemoattractants that most likely play a role in virus dissemination in the
      host. Analysis of global cellular gene expression revealed activation of innate
      immune responses and the modulation of protein and lipid synthesis to accommodate
      latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited
      selective responses to secondary stimuli known to induce an antiviral state.
      Furthermore, when challenged with type I and II interferon, latently infected
      cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation.
      The data demonstrate that HCMV reprograms specific cellular pathways in
      monocytes, most notably innate immune responses, which may play a role in the
      establishment of, maintenance of, and reactivation from latency. The modulation
      of innate immune responses is likely a viral evasion strategy contributing to
      viral dissemination and pathogenesis in the host. IMPORTANCE: HCMV has the
      ability to establish a lifelong infection within the host, a phenomenon termed
      latency. We have established a short-term model system in human peripheral blood
      monocytes to study the immunological relevance of latent virus carriage.
      Infection of CD14(+) monocytes by HCMV results in the generation of latency
      specific transcripts, maintenance of viral genomes, and the capacity to reenter
      the lytic cycle. During short-term latency in monocytes the virus initiates a
      program of differentiation to inflammatory macrophages that coincides with the
      modulation of cytokine secretion and specific cellular processes. HCMV-infected
      monocytes are hindered in their capacity to exert normal immunoprotective
      mechanisms. Additionally, latent virus disrupts type I and II interferon
      signaling at the level of STAT1 phosphorylation. This in vitro model system can
      significantly contribute to our understanding of the molecular and inflammatory
      factors that initiate HCMV reactivation in the host and allow the development of
      strategies to eradicate virus persistence.

PMID- 24920804
TI  - STAT4 deficiency fails to induce lung Th2 or Th17 immunity following primary or
      secondary respiratory syncytial virus (RSV) challenge but enhances the lung RSV
      specific CD8+ T cell immune response to secondary challenge.
AB  - Immune-mediated lung injury is a hallmark of lower respiratory tract illness
      caused by respiratory syncytial virus (RSV). STAT4 plays a critical role in CD4+
      Th1 lineage differentiation and gamma interferon (IFN-gamma) protein expression
      by CD4+ T cells. As CD4+ Th1 differentiation is associated with negative
      regulation of CD4+ Th2 and Th17 differentiation, we hypothesized that RSV
      infection of STAT4-/- mice would result in enhanced lung Th2 and Th17
      inflammation and impaired lung Th1 inflammation compared to wild-type (WT) mice.
      We performed primary and secondary RSV challenges in WT and STAT4-/- mice and
      used STAT1-/- mice as a positive control for the development of RSV-specific lung
      Th2 and Th17 inflammation during primary challenge. Primary RSV challenge of
      STAT4-/- mice resulted in decreased T-bet and IFN-gamma expression levels in CD4+
      T cells compared to those of WT mice. Lung Th2 and Th17 inflammation did not
      develop in primary RSV-challenged STAT4-/- mice. Decreased IFN-gamma expression
      by NK cells, CD4+ T cells, and CD8+ T cells was associated with attenuated weight
      loss and enhanced viral clearance with primary challenge in STAT4-/- mice
      compared to WT mice. Following secondary challenge, WT and STAT4-/- mice also did
      not develop lung Th2 or Th17 inflammation. In contrast to primary challenge,
      secondary RSV challenge of STAT4-/- mice resulted in enhanced weight loss, an
      increased lung IFN-gamma expression level, and an increased lung RSV-specific
      CD8+ T cell response compared to those of WT mice. These data demonstrate that
      STAT4 regulates the RSV-specific CD8+ T cell response to secondary infection but
      does not independently regulate lung Th2 or Th17 immune responses to RSV
      challenge. IMPORTANCE: STAT4 is a protein critical for both innate and adaptive
      immune responses to viral infection. Our results show that STAT4 regulates the
      immune response to primary and secondary challenge with RSV but does not restrain
      RSV-induced lung Th2 or Th17 immune responses. These findings suggest that STAT4
      expression may influence lung immunity and severity of illness following primary
      and secondary RSV infections.

PMID- 24920805
TI  - CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus
      SIV239 vaccine enhances SIV-specific humoral and cellular immunity and improves
      protection against a heterologous SIVE660 mucosal challenge.
AB  - It remains a challenge to develop a successful human immunodeficiency virus (HIV)
      vaccine that is capable of preventing infection. Here, we utilized the benefits
      of CD40L, a costimulatory molecule that can stimulate both dendritic cells (DCs)
      and B cells, as an adjuvant for our simian immunodeficiency virus (SIV) DNA
      vaccine in rhesus macaques. We coexpressed the CD40L with our DNA/SIV vaccine
      such that the CD40L is anchored on the membrane of SIV virus-like particle (VLP).
      These CD40L containing SIV VLPs showed enhanced activation of DCs in vitro. We
      then tested the potential of DNA/SIV-CD40L vaccine to adjuvant the DNA prime of a
      DNA/modified vaccinia virus Ankara (MVA) vaccine in rhesus macaques. Our results
      demonstrated that the CD40L adjuvant enhanced the functional quality of anti-Env
      antibody response and breadth of anti-SIV CD8 and CD4 T cell responses,
      significantly delayed the acquisition of heterologous mucosal SIV infection, and
      improved viral control. Notably, the CD40L adjuvant enhanced the control of viral
      replication in the gut at the site of challenge that was associated with lower
      mucosal CD8 immune activation, one of the strong predictors of disease
      progression. Collectively, our results highlight the benefits of CD40L adjuvant
      for enhancing antiviral humoral and cellular immunity, leading to enhanced
      protection against a pathogenic SIV. A single adjuvant that enhances both humoral
      and cellular immunity is rare and thus underlines the importance and practicality
      of CD40L as an adjuvant for vaccines against infectious diseases, including HIV
      1. IMPORTANCE: Despite many advances in the field of AIDS research, an effective
      AIDS vaccine that can prevent infection remains elusive. CD40L is a key
      stimulator of dendritic cells and B cells and can therefore enhance T cell and
      antibody responses, but its overly potent nature can lead to adverse effects
      unless used in small doses. In order to modulate local expression of CD40L at
      relatively lower levels, we expressed CD40L in a membrane-bound form, along with
      SIV antigens, in a nucleic acid (DNA) vector. We tested the immunogenicity and
      efficacy of the CD40L-adjuvanted vaccine in macaques using a heterologous mucosal
      SIV infection. The CD40L-adjuvanted vaccine enhanced the functional quality of
      anti-Env antibody response and breadth of anti-SIV T cell responses and improved
      protection. These results demonstrate that VLP-membrane-bound CD40L serves as a
      novel adjuvant for an HIV vaccine.

PMID- 24920806
TI  - A novel mode of poxvirus superinfection exclusion that prevents fusion of the
      lipid bilayers of viral and cellular membranes.
AB  - Superinfection exclusion is a widespread phenomenon that prevents secondary
      infections by closely related viruses. The vaccinia virus A56 and K2 proteins in
      the cell membrane can prevent superinfection by interacting with the entry-fusion
      complex of subsequent viruses. Here, we described another form of exclusion that
      is established earlier in infection and does not require the A56 or K2 protein.
      Cells infected with one or more infectious virions excluded hundreds of
      superinfecting vaccinia virus particles. A related orthopoxvirus, but neither a
      flavivirus nor a rhabdovirus, was also excluded, indicating selectivity. Although
      superinfecting vaccinia virus bound to cells, infection was inhibited at the
      membrane fusion step, thereby preventing core entry into the cytoplasm and early
      gene expression. In contrast, A56/K2 protein-mediated exclusion occurred
      subsequent to membrane fusion. Induction of resistance to superinfection depended
      on viral RNA and protein synthesis by the primary virus but did not require DNA
      replication. Although superinfection resistance correlated with virus-induced
      changes in the cytoskeleton, studies with mutant vaccinia viruses indicated that
      the cytoskeletal changes were not necessary for resistance to superinfection.
      Interferon-inducible transmembrane proteins, which can inhibit membrane fusion in
      other viral systems, did not prevent vaccinia virus membrane fusion, suggesting
      that these interferon-inducible proteins are not involved in superinfection
      exclusion. While the mechanism remains to be determined, the early establishment
      of superinfection exclusion may provide a "winner-take-all" reward to the first
      poxvirus particles that successfully initiate infection and prevent the entry and
      genome reproduction of defective or less fit particles. IMPORTANCE: The
      replication of a virus usually follows a defined sequence of events: attachment,
      entry into the cytoplasm or nucleus, gene expression, genome replication,
      assembly of infectious particles, and spread to other cells. Although multiple
      virus particles may enter a cell at the same time, mechanisms exist to prevent
      infection by subsequent viruses. The latter phenomenon, known as superinfection
      exclusion, can occur by a variety of mechanisms that are not well understood. We
      showed that superinfection by vaccinia virus was prevented at the membrane fusion
      step, which closely followed virion attachment. Thus, neither gene expression nor
      genome replication of the superinfecting virus occurred. Expression of early
      proteins by the primary virus was necessary and sufficient to induce the
      superinfection-resistant state. Superinfection exclusion may be beneficial to
      vaccinia virus by selecting particles that can infect cells rapidly, excluding
      defective particles and synchronizing the replication cycle.

PMID- 24920807
TI  - Cytokine/Chemokine responses in activated CD4+ and CD8+ T cells isolated from
      peripheral blood, bone marrow, and axillary lymph nodes during acute simian
      immunodeficiency virus infection.
AB  - Understanding the cytokine/chemokine networks in CD4(+) and CD8(+) T cells during
      the acute phase of infection is crucial to design therapies for the control of
      early human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV)
      replication. Here, we measured early changes in CD4(+) and CD8(+) T cells in the
      peripheral blood (PB), bone marrow (BM), and axillary lymph node (ALN) tissue of
      rhesus macaques infected with SIVMAC251. At 21 days after infection, all tissues
      showed a statistically significant loss of CD4(+) T cells along with immune
      activation of CD8(+) T cells in PB and ALN tissue. Twenty-eight different
      cytokines/chemokines were quantified in either anti-CD3/28 antibody- or
      staphylococcal enterotoxin B-stimulated single-positive CD4(+) and CD8(+) T
      cells. PB CD4(+) T cells produced predominantly interleukin-2 (IL-2), whereas
      CD4(+) and CD8(+) T-cell subsets in tissues produced beta-chemokines both before
      and 21 days after SIV infection. Tissues generally exhibited massive upregulation
      of many cytokines/chemokines following infection, possibly in an attempt to
      mitigate the loss of CD4(+) T cells. There was no evidence of a T-helper 1 (TH1)
      to-TH2 shift in CD4(+) T cells or a T-cytotoxic 1 (TC1)-to-TC2 cytokine shift in
      CD8(+) T cells in PB, BM, and ALN T-cell subsets during the acute phase of SIV
      infection. Despite the upregulation of several important effector
      cytokines/chemokines (IL-2, IL-12, IL-17, gamma interferon, granulocyte
      macrophage colony-stimulating factor) by CD4(+) and CD8(+) T cells, upregulation
      of beta-chemokines (CCL2 and CCL22), basic fibroblast growth factor (FGF-basic),
      hepatocyte growth factor (HGF), and migration inhibition factor (MIF) may provide
      a poor prognosis either by inducing increased virus replication or by other
      unknown mechanisms. Therefore, drugs targeting beta-chemokines (CCL2 and CCL22),
      FGF-basic, HGF, or MIF might be important for developing effective vaccines and
      therapeutics against HIV. IMPORTANCE: Human immunodeficiency virus (HIV)/simian
      immunodeficiency virus (SIV) infection results in early depletion of CD4(+) T
      cells and dysregulation of protective immune responses. Therefore, understanding
      the cytokine/chemokine networks in CD4(+) and CD8(+) T cells in different tissues
      during the acute phase of infection is crucial to the design of therapies for the
      control of early viral replication. Here, we measured early changes in CD4(+) and
      CD8(+) T cells in peripheral blood (PB), bone marrow (BM), and axillary lymph
      node (ALN) tissue of rhesus macaques infected with SIVMAC251. There was no
      evidence of a T-helper 1 (TH1)-to-TH2 shift in CD4(+) T cells or a T-cytotoxic 1
      (TC1)-to-TC2 cytokine shift in CD8(+) T cells in PB, BM, and ALN T-cell subsets
      during the acute phase of SIV infection. Despite the upregulation of several
      important effector cytokines/chemokines by CD4(+) and CD8(+) T cells,
      upregulation of beta-chemokines, fibroblast growth factor-basic, hepatocyte
      growth factor, and migration inhibition factor may provide a poor prognosis.

PMID- 24920808
TI  - Sumoylation of influenza A virus nucleoprotein is essential for intracellular
      trafficking and virus growth.
AB  - Viruses take advantage of host posttranslational modifications for their own
      benefit. It was recently reported that influenza A virus proteins interact
      extensively with the host sumoylation system. Thereby, several viral proteins,
      including NS1 and M1, are sumoylated to facilitate viral replication. However, to
      what extent sumoylation is exploited by influenza A virus is not fully
      understood. In this study, we found that influenza A virus nucleoprotein (NP) is
      a bona fide target of sumoylation in both NP-transfected cells and virus-infected
      cells. We further found that NP is sumoylated at the two most N-terminal
      residues, lysines 4 and 7, and that sumoylation at lysine 7 of NP is highly
      conserved across different influenza A virus subtypes and strains, including the
      recently emerged human H7N9 virus. While NP stability and polymerase activity are
      little affected by sumoylation, the NP sumoylation-defective WSN-NPK4,7R virus
      exhibited early cytoplasmic localization of NP. The growth of the WSN-NPK4,7R
      virus was highly attenuated compared to that of the wild-type WSN virus, and the
      lysine residue at position 7 is indispensable for the virus's survival, as
      illustrated by the rapid emergence of revertant viruses. Thus, sumoylation of
      influenza A virus NP is essential for intracellular trafficking of NP and for
      virus growth, illustrating sumoylation as a crucial strategy extensively
      exploited by influenza A virus for survival in its host. IMPORTANCE: Host
      posttranslational modifications are heavily targeted by viruses for their own
      benefit. We and others previously reported that influenza A virus interacts
      extensively with the host sumoylation system. However, the functional outcomes of
      viral sumoylation are not fully understood. Here we found that influenza A virus
      nucleoprotein (NP), an essential component for virus replication, is a new target
      of SUMO. This is the first study to find that NP from different influenza A
      viruses, including recently emerged H7N9, is sumoylated at conserved lysine 7.
      Our data further illustrated that sumoylation of influenza A virus NP is
      essential for intracellular trafficking of NP and virus growth, indicating that
      influenza A virus relies deeply on sumoylation to survive in host cells.
      Strategies to downregulate viral sumoylation could thus be a potential antiviral
      treatment.

PMID- 24920809
TI  - Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose
      a CD4-inducible epitope and block the interaction of HIV-1 gp140 with
      galactosylceramide.
AB  - Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated
      to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial
      cells. Disruption of the HIV-1 Env interaction with such alternate receptors
      could be one strategy to prevent HIV-1 entry through the mucosal barrier. To
      study antibody modulation of HIV-1 Env-Galcer interactions, we used Galcer
      containing liposomes to assess whether natural- and vaccine-induced monoclonal
      antibodies can block HIV-1 Env binding to Galcer. HIV-1 Env gp140 proteins bound
      to Galcer liposomes with Kds (dissociation constants) in the nanomolar range.
      Several HIV-1 ALVAC/AIDSVAX vaccinee-derived monoclonal antibodies (MAbs)
      specific for the gp120 first constant (C1) region blocked Galcer binding of a
      transmitted/founder HIV-1 Env gp140. Among the C1-specific MAbs that showed
      Galcer blocking, the antibody-dependent cellular cytotoxicity-mediating CH38 IgG
      and its natural IgA isotype were the most potent blocking antibodies. C1-specific
      IgG monoclonal antibodies that blocked Env binding to Galcer induced upregulation
      of the gp120 CD4-inducible (CD4i) epitope bound by MAb 17B, demonstrating that a
      conformational change in gp120 may be required for Galcer blocking. However, the
      MAb 17B itself did not block Env-Galcer binding, suggesting that the C1 antibody
      induced gp120 conformational changes resulted in alteration in a Galcer binding
      site distant from the CD4i 17B MAb binding site. IMPORTANCE: Galactosyl ceramide,
      a glycosphingolipid, has been postulated to be a receptor for the HIV-1 envelope
      glycoprotein (Env) interaction with mucosal epithelial cells. Here, we have
      mimicked this interaction by using an artificial membrane containing synthetic
      Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block
      the HIV-1 Env-Galcer interaction. Our study revealed that a class of vaccine
      induced human antibodies potently blocks HIV-1 Env-Galcer binding by perturbing
      the HIV-1 Env conformation.

PMID- 24920810
TI  - Modulation of Kaposi's sarcoma-associated herpesvirus interleukin-6 function by
      hypoxia-upregulated protein 1.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8)
      is linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma
      (PEL), and multicentric Castleman's disease (MCD). KSHV expresses several
      proteins that modulate host cell signaling pathways. One of these proteins is
      viral interleukin-6 (vIL-6), which is a homolog of human IL-6 (hIL-6). vIL-6 is
      able to prevent apoptosis and promote proinflammatory signaling, angiogenesis,
      and cell proliferation. Although it can be secreted, vIL-6 is mainly an
      intracellular protein that is retained in the endoplasmic reticulum (ER). We
      performed affinity purification and mass spectrometry to identify novel vIL-6
      binding partners and found that a cellular ER chaperone, hypoxia-upregulated
      protein 1 (HYOU1), interacts with vIL-6. Immunohistochemical staining reveals
      that both PEL and KS tumor tissues express significant amounts of HYOU1. We also
      show that HYOU1 increases endogenous vIL-6 protein levels and that HYOU1
      facilitates vIL-6-induced JAK/STAT signaling, migration, and survival in
      endothelial cells. Furthermore, our data suggest that HYOU1 also modulates vIL
      6's ability to induce CCL2, a chemokine involved in cell migration. Finally, we
      investigated the impact of HYOU1 on cellular hIL-6 signaling. Collectively, our
      data indicate that HYOU1 is important for vIL-6 function and may play a role in
      the pathogenesis of KSHV-associated cancers. IMPORTANCE: KSHV vIL-6 is detectable
      in all KSHV-associated malignancies and promotes tumorigenesis and inflammation.
      We identified a cellular protein, called hypoxia-upregulated protein 1 (HYOU1),
      that interacts with KSHV vIL-6 and is present in KSHV-infected tumors. Our data
      suggest that HYOU1 facilitates the vIL-6-induced signaling, migration, and
      survival of endothelial cells.

PMID- 24920811
TI  - Human and host species transferrin receptor 1 use by North American arenaviruses.
AB  - At least five New World (NW) arenaviruses cause hemorrhagic fevers in South
      America. These pathogenic clade B viruses, as well as nonpathogenic arenaviruses
      of the same clade, use transferrin receptor 1 (TfR1) of their host species to
      enter cells. Pathogenic viruses are distinguished from closely related
      nonpathogenic ones by their additional ability to utilize human TfR1 (hTfR1).
      Here, we investigate the receptor usage of North American arenaviruses, whose
      entry proteins share greatest similarity with those of the clade B viruses. We
      show that all six North American arenaviruses investigated utilize host species
      TfR1 orthologs and present evidence consistent with arenavirus-mediated selection
      pressure on the TfR1 of the North American arenavirus host species. Notably, one
      of these viruses, AV96010151, closely related to the prototype Whitewater Arroyo
      virus (WWAV), entered cells using hTfR1, consistent with a role for a WWAV-like
      virus in three fatal human infections whose causative agent has not been
      identified. In addition, modest changes were sufficient to convert hTfR1 into a
      functional receptor for most of these viruses, suggesting that a minor alteration
      in virus entry protein may allow these viruses to use hTfR1. Our data establish
      TfR1 as a cellular receptor for North American arenaviruses, highlight an "arms
      race" between these viruses and their host species, support the association of
      North American arenavirus with fatal human infections, and suggest that these
      viruses have a higher potential to emerge and cause human diseases than has
      previously been appreciated. IMPORTANCE: hTfR1 use is a key determinant for a NW
      arenavirus to cause hemorrhagic fevers in humans. All known pathogenic NW
      arenaviruses are transmitted in South America by their host rodents. North
      American arenaviruses are generally considered nonpathogenic, but some of these
      viruses have been tentatively implicated in human fatalities. We show that these
      North American arenaviruses use the TfR1 orthologs of their rodent host species
      and identify TfR1 polymorphisms suggesting an ongoing "arms race" between these
      viruses and their hosts. We also show that a close relative of a North American
      arenavirus suggested to have caused human fatalities, the Whitewater Arroyo
      species complex virus AV96010151, uses human TfR1. Moreover, we present data that
      imply that modest changes in other North American arenaviruses might allow these
      viruses to infect humans. Collectively, our data suggest that North American
      arenaviruses have a higher potential to cause human disease than previously
      assumed.

PMID- 24920812
TI  - Hepatitis A virus 3C protease cleaves NEMO to impair induction of beta
      interferon.
AB  - NEMO (NF-kappaB essential modulator) is a bridging adaptor indispensable for
      viral activation of interferon (IFN) antiviral response. Herein, we show that
      hepatitis A virus (HAV) 3C protease (3Cpro) cleaves NEMO at the Q304 residue,
      negating its signaling adaptor function and abrogating viral induction of IFN
      beta synthesis via the retinoic acid-inducible gene I/melanoma differentiation
      associated protein 5 (RIG-I/MDA5) and Toll-like receptor 3 (TLR3) pathways. NEMO
      cleavage and IFN antagonism, however, were lost upon ablation of the catalytic
      activity of 3Cpro. These data describe a novel immune evasion mechanism of HAV.

PMID- 24920814
TI  - The herpes simplex virus 1 virion host shutoff protein enhances translation of
      viral late mRNAs by preventing mRNA overload.
AB  - We recently demonstrated that the virion host shutoff (vhs) protein, an mRNA
      specific endonuclease, is required for efficient herpes simplex virus 1 (HSV-1)
      replication and translation of viral true-late mRNAs, but not other viral and
      cellular mRNAs, in many cell types (B. Dauber, J. Pelletier, and J. R. Smiley, J.
      Virol. 85:5363-5373, 2011, http://dx.doi.org/10.1128/JVI.00115-11). Here, we
      evaluated whether the structure of true-late mRNAs or the timing of their
      transcription is responsible for the poor translation efficiency in the absence
      of vhs. To test whether the highly structured 5' untranslated region (5'UTR) of
      the true-late gC mRNA is the primary obstacle for translation initiation, we
      replaced it with the less structured 5'UTR of the gamma-actin mRNA. However, this
      mutation did not restore translation in the context of a vhs-deficient virus. We
      then examined whether the timing of transcription affects translation efficiency
      at late times. To this end, we engineered a vhs-deficient virus mutant that
      transcribes the true-late gene US11 with immediate-early kinetics (IEUS11
      DeltaSma). Interestingly, IEUS11-DeltaSma showed increased translational activity
      on the US11 transcript at late times postinfection, and US11 protein levels were
      restored to wild-type levels. These results suggest that mRNAs can maintain
      translational activity throughout the late stage of infection if they are present
      before translation factors and/or ribosomes become limiting. Taken together,
      these results provide evidence that in the absence of the mRNA-destabilizing
      function of vhs, accumulation of viral mRNAs overwhelms the capacity of the host
      translational machinery, leading to functional exclusion of the last mRNAs that
      are made during infection. IMPORTANCE: The process of mRNA translation accounts
      for a significant portion of a cell's energy consumption. To ensure efficient use
      of cellular resources, transcription, translation, and mRNA decay are tightly
      linked and highly regulated. However, during virus infection, the overall amount
      of mRNA may increase drastically, possibly overloading the capacity of the
      translation apparatus. Our results suggest that the HSV-1 vhs protein, an mRNA
      specific endoribonuclease, prevents mRNA overload during infection, thereby
      allowing translation of late viral mRNAs. The requirement for vhs varies between
      cell types. Further studies of the basis for this difference likely will offer
      insights into how cells regulate overall mRNA levels and access to the
      translational apparatus.

PMID- 24920813
TI  - Genomic flexibility of human endogenous retrovirus type K.
AB  - Human endogenous retrovirus type K (HERV-K) proviruses are scattered throughout
      the human genome, but as no infectious HERV-K virus has been detected to date,
      the mechanism by which these viruses replicated and populated the genome remains
      unresolved. Here, we provide evidence that, in addition to the RNA genomes that
      canonical retroviruses package, modern HERV-K viruses can contain reverse
      transcribed DNA (RT-DNA) genomes. Indeed, reverse transcription of genomic HERV-K
      RNA into the DNA form is able to occur in three distinct times and locations: (i)
      in the virus-producing cell prior to viral release, yielding a DNA-containing
      extracellular virus particle similar to the spumaviruses; (ii) within the
      extracellular virus particle itself, transitioning from an RNA-containing
      particle to a DNA-containing particle; and (iii) after entry of the RNA
      containing virus into the target cell, similar to canonical retroviruses, such as
      murine leukemia virus and HIV. Moreover, using a resuscitated HERV-K virus
      construct, we show that both viruses with RNA genomes and viruses with DNA
      genomes are capable of infecting target cells. This high level of genomic
      flexibility historically could have permitted these viruses to replicate in
      various host cell environments, potentially assisting in their many integration
      events and resulting in their high prevalence in the human genome. Moreover, the
      ability of modern HERV-K viruses to proceed through reverse transcription and
      package RT-DNA genomes suggests a higher level of replication competency than was
      previously understood, and it may be relevant in HERV-K-associated human
      diseases. IMPORTANCE: Retroviral elements comprise at least 8% of the human
      genome. Of all the endogenous retroviruses, HERV-K viruses are the most intact
      and biologically active. While a modern infectious HERV-K has yet to be found,
      HERV-K activation has been associated with cancers, autoimmune diseases, and HIV
      1 infection. Thus, determining how this virus family became such a prevalent
      member of our genome and what it is capable of in its current form are of the
      utmost importance. Here, we provide evidence that HERV-K viruses currently found
      in the human genome are able to proceed through reverse transcription and
      historically utilized a life cycle with a surprising degree of genomic
      flexibility in which both RNA- and DNA-containing viruses were capable of
      mediating infection.

PMID- 24920815
TI  - Newcastle disease virus vector producing human norovirus-like particles induces
      serum, cellular, and mucosal immune responses in mice.
AB  - Human norovirus infection is the most common cause of viral gastroenteritis
      worldwide. Development of an effective vaccine is required for reducing norovirus
      outbreaks. The inability to grow human norovirus in cell culture has hindered the
      development of live-attenuated vaccines. To overcome this obstacle, we generated
      a recombinant Newcastle disease virus (rNDV)-vectored experimental norovirus
      vaccine by expressing the capsid protein (VP1) of norovirus strain VA387. We
      compared two different NDV vectors, a conventional rNDV vector and a modified
      rNDV vector, for their efficiencies in expressing VP1 protein. Our results showed
      that the modified vector replicated to higher titers and expressed higher levels
      of VP1 protein in DF1 cells and in allantoic fluid of embryonated chicken eggs
      than did the conventional vector. We further demonstrated that the VP1 protein
      produced by rNDVs was able to self-assemble into virus-like particles (VLPs) that
      are morphologically similar to baculovirus-expressed VLPs. Evaluation of their
      immunogenicity in mice showed that the modified rNDV vector induced a higher
      level of IgG response than those induced by the conventional vector and by the
      baculovirus-expressed VLPs. The rNDV vectors predominantly induced IgG2a subclass
      antibody for the Th1 response, and specifically, high levels of gamma interferon
      (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-2 (IL-2)
      were detected in splenocytes. In addition, the modified rNDV vector induced a
      higher level of fecal IgA response in mice than did baculovirus-expressed VLPs.
      Our findings suggest that the rNDV vector is an efficient system to produce cost
      effective VLPs in embryonated chicken eggs and has the potential to be used as a
      live-attenuated vaccine in humans. IMPORTANCE: Noroviruses are the major cause of
      viral gastroenteritis worldwide. Currently, effective vaccines against norovirus
      infection are not available. In this study, we have evaluated Newcastle disease
      virus (NDV) as a vaccine vector for norovirus. Our results suggest that NDV can
      be used not only as a cost-effective method for large-scale production of
      norovirus-like particle vaccines but also as a live-attenuated vectored vaccine.

PMID- 24920816
TI  - The tegument protein pp65 of human cytomegalovirus acts as an optional scaffold
      protein that optimizes protein uploading into viral particles.
AB  - The mechanisms that lead to the tegumentation of herpesviral particles are only
      poorly defined. The phosphoprotein 65 (pp65) is the most abundant constituent of
      the virion tegument of human cytomegalovirus (HCMV). It is, however, nonessential
      for virion formation. This seeming discrepancy has not met with a satisfactory
      explanation regarding the role of pp65 in HCMV particle morphogenesis. Here, we
      addressed the question of how the overall tegument composition of the HCMV virion
      depended on pp65 and how the lack of pp65 influenced the packaging of particular
      tegument proteins. To investigate this, we analyzed the proteomes of pp65
      positive (pp65pos) and pp65-negative (pp65neg) virions by label-free quantitative
      mass spectrometry and determined the relative abundances of tegument proteins.
      Surprisingly, only pUL35 was elevated in pp65neg virions. As the abundance of
      pUL35 in the HCMV tegument is low, it is unlikely that it replaced pp65 as a
      structural component in pp65neg virions. A subset of proteins, including the
      third most abundant tegument protein, pUL25, as well as pUL43, pUL45, and pUL71,
      were reduced in pp65neg or pp65low virions, indicating that the packaging of
      these proteins was related to pp65. The levels of tegument components, like pp28
      and the capsid-associated tegument proteins pp150, pUL48, and pUL47, were
      unaffected by the lack of pp65. Our analyses demonstrate that deletion of pp65 is
      not compensated for by other viral proteins in the process of virion
      tegumentation. The results are concordant with a model of pp65 serving as an
      optional scaffold protein that facilitates protein upload into the outer tegument
      of HCMV particles. IMPORTANCE: The assembly of the tegument of herpesviruses is
      only poorly understood. Particular proteins, like HCMV pp65, are abundant
      tegument constituents. pp65 is thus considered to play a major role in tegument
      assembly in the process of virion morphogenesis. We show here that deletion of
      the pp65 gene leads to reduced packaging of a subset of viral proteins,
      indicating that pp65 acts as an optional scaffold protein mediating protein
      upload into the tegument.

PMID- 24920817
TI  - Unfixed endogenous retroviral insertions in the human population.
AB  - One lineage of human endogenous retroviruses (HERVs), HERV-K(HML2), is
      upregulated in many cancers, some autoimmune/inflammatory diseases, and HIV
      infected cells. Despite 3 decades of research, it is not known if these viruses
      play a causal role in disease, and there has been recent interest in whether they
      can be used as immunotherapy targets. Resolution of both these questions will be
      helped by an ability to distinguish between the effects of different integrated
      copies of the virus (loci). Research so far has concentrated on the 20 or so
      recently integrated loci that, with one exception, are in the human reference
      genome sequence. However, this viral lineage has been copying in the human
      population within the last million years, so some loci will inevitably be present
      in the human population but absent from the reference sequence. We therefore
      performed the first detailed search for such loci by mining whole-genome
      sequences generated by next-generation sequencing. We found a total of 17 loci,
      and the frequency of their presence ranged from only 2 of the 358 individuals
      examined to over 95% of them. On average, each individual had six loci that are
      not in the human reference genome sequence. Comparing the number of loci that we
      found to an expectation derived from a neutral population genetic model suggests
      that the lineage was copying until at least ~250,000 years ago. IMPORTANCE: About
      5% of the human genome sequence is composed of the remains of retroviruses that
      over millions of years have integrated into the chromosomes of egg and/or sperm
      precursor cells. There are indications that protein expression of these viruses
      is higher in some diseases, and we need to know (i) whether these viruses have a
      role in causing disease and (ii) whether they can be used as immunotherapy
      targets in some of them. Answering both questions requires a better understanding
      of how individuals differ in the viruses that they carry. We carried out the
      first careful search for new viruses in some of the many human genome sequences
      that are now available thanks to advances in sequencing technology. We also
      compared the number that we found to a theoretical expectation to see if it is
      likely that these viruses are still replicating in the human population today.

PMID- 24920818
TI  - Comprehensive analysis of contributions from protein conformational stability and
      major histocompatibility complex class II-peptide binding affinity to CD4+
      epitope immunogenicity in HIV-1 envelope glycoprotein.
AB  - Helper T-cell epitope dominance in human immunodeficiency virus type 1 (HIV-1)
      envelope glycoprotein gp120 is not adequately explained by peptide binding to
      major histocompatibility complex (MHC) proteins. Antigen processing potentially
      influences epitope dominance, but few, if any, studies have attempted to
      reconcile the influences of antigen processing and MHC protein binding for all
      helper T-cell epitopes of an antigen. Epitopes of gp120 identified in both humans
      and mice occur on the C-terminal flanks of flexible segments that are likely to
      be proteolytic cleavage sites. In this study, the influence of gp120 conformation
      on the dominance pattern in gp120 from HIV strain 89.6 was examined in CBA mice,
      whose MHC class II protein has one of the most well defined peptide-binding
      preferences. Only one of six dominant epitopes contained the most conserved
      element of the I-Ak binding motif, an aspartic acid. Destabilization of the gp120
      conformation by deletion of single disulfide bonds preferentially enhanced
      responses to the cryptic I-Ak motif-containing sequences, as reported by T-cell
      proliferation or cytokine secretion. Conversely, inclusion of CpG in the adjuvant
      with gp120 enhanced responses to the dominant CD4+ T-cell epitopes. The gp120
      destabilization affected secretion of some cytokines more than others, suggesting
      that antigen conformation could modulate T-cell functions through mechanisms of
      antigen processing. IMPORTANCE: CD4+ helper T cells play an essential role in
      protection against HIV and other pathogens. Thus, the sites of helper T-cell
      recognition, the dominant epitopes, are targets for vaccine design; and the
      corresponding T cells may provide markers for monitoring infection and immunity.
      However, T-cell epitopes are difficult to identify and predict. It is also
      unclear whether CD4+ T cells specific for one epitope are more protective than T
      cells specific for other epitopes. This work shows that the three-dimensional
      (3D) structure of an HIV protein partially determines which epitopes are
      dominant, most likely by controlling the breakdown of HIV into peptides.
      Moreover, some types of signals from CD4+ T cells are affected by the HIV protein
      3D structure; and thus the protectiveness of a particular peptide vaccine could
      be related to its location in the 3D structure.

PMID- 24920819
TI  - Influenza virus infectivity and virulence following ocular-only aerosol
      inoculation of ferrets.
AB  - Respiratory pathogens have traditionally been studied by examining the exposure
      and infection of respiratory tract tissues. However, these studies typically
      overlook the role of ocular surfaces, which represent both a potential site of
      virus replication and a portal of entry for the establishment of a respiratory
      infection. To model transocular virus entry in a mammalian species, we
      established a novel inoculation method that delivers an aerosol inoculum
      exclusively to the ferret ocular surface. Using influenza virus as a
      representative respiratory pathogen, we found that both human and avian viruses
      mounted productive respiratory infections in ferrets following ocular-only
      aerosol inoculation, and we demonstrated that H5N1 virus can result in a fatal
      infection at doses below 10 PFU or with exposure times as short as 2 min. Ferrets
      inoculated by the ocular aerosol route with an avian (H7N7, H7N9) or human (H1N1,
      H3N2v) virus were capable of transmitting the virus to naive animals in direct
      contact or respiratory-droplet models, respectively. Our results reveal that
      ocular-only exposure to virus-containing aerosols constitutes a valid exposure
      route for a potentially fatal respiratory infection, even for viruses that do not
      demonstrate an ocular tropism, underscoring the public health implications of
      ocular exposure in clinical or occupational settings. IMPORTANCE: In the absence
      of eye protection, the human ocular surface remains vulnerable to infection with
      aerosolized respiratory viruses. In this study, we present a way to inoculate
      laboratory mammals that excludes respiratory exposure, infecting ferrets only by
      ocular exposure to influenza virus-containing aerosols. This study demonstrates
      that the use of respiratory protection alone does not fully protect against
      influenza virus exposure, infection, and severe disease.

PMID- 24920820
TI  - Mapping of functional domains of the lipid kinase phosphatidylinositol 4-kinase
      type III alpha involved in enzymatic activity and hepatitis C virus replication.
AB  - The lipid kinase phosphatidylinositol 4-kinase III alpha (PI4KIIIalpha) is an
      endoplasmic reticulum (ER)-resident enzyme that synthesizes phosphatidylinositol
      4-phosphate (PI4P). PI4KIIIalpha is an essential host factor for hepatitis C
      virus (HCV) replication. Interaction with HCV nonstructural protein 5A (NS5A)
      leads to kinase activation and accumulation of PI4P at intracellular membranes.
      In this study, we investigated the structural requirements of PI4KIIIalpha in HCV
      replication and enzymatic activity. Therefore, we analyzed PI4KIIIalpha mutants
      for subcellular localization, reconstitution of HCV replication in PI4KIIIalpha
      knockdown cell lines, PI4P induction in HCV-positive cells, and lipid kinase
      activity in vitro. All mutants still interacted with NS5A and localized in a
      manner similar to that of the full-length enzyme, suggesting multiple regions of
      PI4KIIIalpha are involved in NS5A interaction and subcellular localization.
      Interestingly, the N-terminal 1,152 amino acids were dispensable for HCV
      replication, PI4P induction, and enzymatic function, whereas further N-terminal
      or C-terminal deletions were deleterious, thereby defining the minimal
      PI4KIIIalpha core enzyme at a size of ca. 108 kDa. Additional deletion of
      predicted functional motifs within the C-terminal half of PI4KIIIalpha also were
      detrimental for enzymatic activity and for the ability of PI4KIIIalpha to rescue
      HCV replication, with the exception of a proposed nuclear localization signal,
      suggesting that the entire C-terminal half of PI4KIIIalpha is involved in the
      formation of a minimal enzymatic core. This view was supported by structural
      modeling of the PI4KIIIalpha C terminus, suggesting a catalytic center formed by
      an N- and C-terminal lobe and an armadillo-fold motif, which is preceded by three
      distinct alpha-helical domains probably involved in regulation of enzymatic
      activity. IMPORTANCE: The lipid kinase PI4KIIIalpha is of central importance for
      cellular phosphatidylinositol metabolism and is a key host cell factor of
      hepatitis C virus replication. However, little is known so far about the
      structure of this 240-kDa protein and the functional importance of specific
      subdomains regarding lipid kinase activity and viral replication. This work
      focuses on the phenotypic analysis of distinct PI4KIIIalpha mutants in different
      biochemical and cell-based assays and develops a structural model of the C
      terminal enzymatic core. The results shed light on the structural and functional
      requirements of enzymatic activity and the determinants required for HCV
      replication.

PMID- 24920821
TI  - Endosomal trafficking of nanoformulated antiretroviral therapy facilitates drug
      particle carriage and HIV clearance.
AB  - Limitations of antiretroviral therapy (ART) include poor patient adherence, drug
      toxicities, viral resistance, and failure to penetrate viral reservoirs. Recent
      developments in nanoformulated ART (nanoART) could overcome such limitations. To
      this end, we now report a novel effect of nanoART that facilitates drug depots
      within intracellular compartments at or adjacent to the sites of the viral
      replication cycle. Poloxamer 407-coated nanocrystals containing the protease
      inhibitor atazanavir (ATV) were prepared by high-pressure homogenization. These
      drug particles readily accumulated in human monocyte-derived macrophages (MDM).
      NanoATV concentrations were ~1,000 times higher in cells than those that could be
      achieved by the native drug. ATV particles in late and recycling endosome
      compartments were seen following pulldown by immunoaffinity chromatography with
      Rab-specific antibodies conjugated to magnetic beads. Confocal microscopy
      provided cross validation by immunofluorescent staining of the compartments.
      Mathematical modeling validated drug-endosomal interactions. Measures of reverse
      transcriptase activity and HIV-1 p24 levels in culture media and cells showed
      that such endosomal drug concentrations enhanced antiviral responses up to 1,000
      fold. We conclude that late and recycling endosomes can serve as depots for
      nanoATV. The colocalization of nanoATV at endosomal sites of viral assembly and
      its slow release sped antiretroviral activities. Long-acting nanoART can serve as
      a drug carrier in both cells and subcellular compartments and, as such, can
      facilitate viral clearance. IMPORTANCE: The need for long-acting ART is
      significant and highlighted by limitations in drug access, toxicity, adherence,
      and reservoir penetrance. We propose that targeting nanoformulated drugs to
      infected tissues, cells, and subcellular sites of viral replication may improve
      clinical outcomes. Endosomes are sites for human immunodeficiency virus assembly,
      and increasing ART concentrations in such sites enhances viral clearance. The
      current work uncovers a new mechanism by which nanoART can enhance viral
      clearance over native drug formulations.

PMID- 24920822
TI  - Kinetochore-microtubule attachment throughout mitosis potentiated by the
      elongated stalk of the kinetochore kinesin CENP-E.
AB  - Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole
      proximal chromosomes during congression in prometaphase. During metaphase, it
      facilitates kinetochore-microtubule end-on attachment required to achieve and
      maintain chromosome alignment. In vitro CENP-E can walk processively along
      microtubule tracks and follow both growing and shrinking microtubule plus ends.
      Neither the CENP-E-dependent transport along microtubules nor its tip-tracking
      activity requires the unusually long coiled-coil stalk of CENP-E. The biological
      role for the CENP-E stalk has now been identified through creation of "Bonsai"
      CENP-E with significantly shortened stalk but wild-type motor and tail domains.
      We demonstrate that Bonsai CENP-E fails to bind microtubules in vitro unless a
      cargo is contemporaneously bound via its C-terminal tail. In contrast, both full
      length and truncated CENP-E that has no stalk and tail exhibit robust motility
      with and without cargo binding, highlighting the importance of CENP-E stalk for
      its activity. Correspondingly, kinetochore attachment to microtubule ends is
      shown to be disrupted in cells whose CENP-E has a shortened stalk, thereby
      producing chromosome misalignment in metaphase and lagging chromosomes during
      anaphase. Together these findings establish an unexpected role of CENP-E
      elongated stalk in ensuring stability of kinetochore-microtubule attachments
      during chromosome congression and segregation. 

PMID- 24920823
TI  - Cdk1 promotes cytokinesis in fission yeast through activation of the septation
      initiation network.
AB  - In Schizosaccharomyces pombe, late mitotic events are coordinated with
      cytokinesis by the septation initiation network (SIN), an essential spindle pole
      body (SPB)-associated kinase cascade, which controls the formation, maintenance,
      and constriction of the cytokinetic ring. It is not fully understood how SIN
      initiation is temporally regulated, but it depends on the activation of the
      GTPase Spg1, which is inhibited during interphase by the essential bipartite
      GTPase-activating protein Byr4-Cdc16. Cells are particularly sensitive to the
      modulation of Byr4, which undergoes cell cycle-dependent phosphorylation presumed
      to regulate its function. Polo-like kinase, which promotes SIN activation, is
      partially responsible for Byr4 phosphorylation. Here we show that Byr4 is also
      controlled by cyclin-dependent kinase (Cdk1)-mediated phosphorylation. A Cdk1
      nonphosphorylatable Byr4 phosphomutant displays severe cell division defects,
      including the formation of elongated, multinucleate cells, failure to maintain
      the cytokinetic ring, and compromised SPB association of the SIN kinase Cdc7. Our
      analyses show that Cdk1-mediated phosphoregulation of Byr4 facilitates complete
      removal of Byr4 from metaphase SPBs in concert with Plo1, revealing an unexpected
      role for Cdk1 in promoting cytokinesis through activation of the SIN pathway. 

PMID- 24920824
TI  - Subcellular optogenetic inhibition of G proteins generates signaling gradients
      and cell migration.
AB  - Cells sense gradients of extracellular cues and generate polarized responses such
      as cell migration and neurite initiation. There is static information on the
      intracellular signaling molecules involved in these responses, but how they
      dynamically orchestrate polarized cell behaviors is not well understood. A
      limitation has been the lack of methods to exert spatial and temporal control
      over specific signaling molecules inside a living cell. Here we introduce
      optogenetic tools that act downstream of native G protein-coupled receptor
      (GPCRs) and provide direct control over the activity of endogenous heterotrimeric
      G protein subunits. Light-triggered recruitment of a truncated regulator of G
      protein signaling (RGS) protein or a Gbetagamma-sequestering domain to a selected
      region on the plasma membrane results in localized inhibition of G protein
      signaling. In immune cells exposed to spatially uniform chemoattractants, these
      optogenetic tools allow us to create reversible gradients of signaling activity.
      Migratory responses generated by this approach show that a gradient of active G
      protein alphai and betagamma subunits is sufficient to generate directed cell
      migration. They also provide the most direct evidence so for a global inhibition
      pathway triggered by Gi signaling in directional sensing and adaptation. These
      optogenetic tools can be applied to interrogate the mechanistic basis of other
      GPCR-modulated cellular functions. 

PMID- 24920825
TI  - Common regulatory control of CTP synthase enzyme activity and filament formation.
AB  - The ability of enzymes to assemble into visible supramolecular complexes is a
      widespread phenomenon. Such complexes have been hypothesized to play a number of
      roles; however, little is known about how the regulation of enzyme activity is
      coupled to the assembly/disassembly of these cellular structures. CTP synthase is
      an ideal model system for addressing this question because its activity is
      regulated via multiple mechanisms and its filament-forming ability is
      evolutionarily conserved. Our structure-function studies of CTP synthase in
      Saccharomyces cerevisiae reveal that destabilization of the active tetrameric
      form of the enzyme increases filament formation, suggesting that the filaments
      comprise inactive CTP synthase dimers. Furthermore, the sites responsible for
      feedback inhibition and allosteric activation control filament length, implying
      that multiple regions of the enzyme can influence filament structure. In
      contrast, blocking catalysis without disrupting the regulatory sites of the
      enzyme does not affect filament formation or length. Together our results argue
      that the regulatory sites that control CTP synthase function, but not enzymatic
      activity per se, are critical for controlling filament assembly. We predict that
      the ability of enzymes to form supramolecular structures in general is closely
      coupled to the mechanisms that regulate their activity. 

PMID- 24920826
TI  - ARH-seq: identification of differential splicing in RNA-seq data.
AB  - The computational prediction of alternative splicing from high-throughput
      sequencing data is inherently difficult and necessitates robust statistical
      measures because the differential splicing signal is overlaid by influencing
      factors such as gene expression differences and simultaneous expression of
      multiple isoforms amongst others. In this work we describe ARH-seq, a discovery
      tool for differential splicing in case-control studies that is based on the
      information-theoretic concept of entropy. ARH-seq works on high-throughput
      sequencing data and is an extension of the ARH method that was originally
      developed for exon microarrays. We show that the method has inherent features,
      such as independence of transcript exon number and independence of differential
      expression, what makes it particularly suited for detecting alternative splicing
      events from sequencing data. In order to test and validate our workflow we
      challenged it with publicly available sequencing data derived from human tissues
      and conducted a comparison with eight alternative computational methods. In order
      to judge the performance of the different methods we constructed a benchmark data
      set of true positive splicing events across different tissues agglomerated from
      public databases and show that ARH-seq is an accurate, computationally fast and
      high-performing method for detecting differential splicing events. 

PMID- 24920827
TI  - G-quadruplex conformation and dynamics are determined by loop length and
      sequence.
AB  - The quadruplex forming G-rich sequences are unevenly distributed throughout the
      human genome. Their enrichment in oncogenic promoters and telomeres has generated
      interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we
      present a quantitative analysis on the conformations and dynamics of GQ forming
      sequences measured by single molecule fluorescence. Additionally, we relate these
      properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our
      result shows that both the loop (non-G components) length and sequence contribute
      to the conformation of the GQ. Real time single molecule traces reveal that the
      folding dynamics also depend on the loop composition. We demonstrate that GQ
      stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and
      the G4R1 protein bind selectively to the parallel GQ conformation. Our findings
      point to the complexity of GQ folding governed by the loop length and sequence
      and how the GQ conformation determines the small molecule and protein binding
      propensity. 

PMID- 24920828
TI  - Structure of the N-glycosidase MilB in complex with hydroxymethyl CMP reveals its
      Arg23 specifically recognizes the substrate and controls its entry.
AB  - 5-Hydroxymethylcytosine (5hmC) is present in T-even phage and mammalian DNA as
      well as some nucleoside antibiotics, including mildiomycin and bacimethrin,
      during whose synthesis 5hmC is produced by the hydrolysis of 5-hydroxymethyl
      cytidine 5'-monophosphate (hmCMP) by an N-glycosidase MilB. Recently, the MilB
      CMP complex structure revealed its substrate specificity for CMP over dCMP.
      However, hmCMP instead of CMP is the preferred substrate for MilB as supported by
      that its KM for CMP is ~27-fold higher than that for hmCMP. Here, we determined
      the crystal structures of MilB and its catalytically inactive E103A mutant in
      complex with hmCMP. In the structure of the complex, Phe22 and Arg23 are
      positioned in a cage-like active site resembling the binding pocket for the
      flipped 5-methylcytosine (5mC) in eukaryotic 5mC-binding proteins. Van der Waals
      interaction between the benzene ring of Phe22 and the pyrimidine ring of hmCMP
      stabilizes its binding. Remarkably, upon hmCMP binding, the guanidinium group of
      Arg23 was bent ~65 degrees  toward hmCMP to recognize its 5-hydroxymethyl group,
      inducing semi-closure of the cage-like pocket. Mutagenesis studies of Arg23 and
      bioinformatics analysis demonstrate that the positively charged Arg/Lys at this
      site is critical for the specific recognition of the 5-hydroxymethyl group of
      hmCMP. 

PMID- 24920829
TI  - A deafness-associated tRNAHis mutation alters the mitochondrial function, ROS
      production and membrane potential.
AB  - In this report, we investigated the molecular genetic mechanism underlying the
      deafness-associated mitochondrial tRNAHis 12201T>C mutation. The destabilization
      of a highly conserved base-pairing (5A-68U) by the m.12201T>C mutation alters
      structure and function of tRNAHis. Using cybrids constructed by transferring
      mitochondria from lymphoblastoid cell lines derived from a Chinese family into
      mtDNA-less (rhoo) cells, we showed ~70% decrease in the steady-state level of
      tRNAHis in mutant cybrids, compared with control cybrids. The mutation changed
      the conformation of tRNAHis, as suggested by slower electrophoretic mobility of
      mutated tRNA with respect to the wild-type molecule. However, ~60% increase in
      aminoacylated level of tRNAHis was observed in mutant cells. The failure in
      tRNAHis metabolism was responsible for the variable reductions in seven mtDNA
      encoded polypeptides in mutant cells, ranging from 37 to 81%, with the average of
      ~46% reduction, as compared with those of control cells. The impaired
      mitochondrial translation caused defects in respiratory capacity in mutant cells.
      Furthermore, marked decreases in the levels of mitochondrial ATP and membrane
      potential were observed in mutant cells. These mitochondrial dysfunctions caused
      an increase in the production of reactive oxygen species in the mutant cells. The
      data provide the evidence for a mitochondrial tRNAHis mutation leading to
      deafness.

PMID- 24920830
TI  - The protein kinase TOUSLED facilitates RNAi in Arabidopsis.
AB  - RNA silencing is an evolutionarily conserved mechanism triggered by double
      stranded RNA that is processed into 21- to 24-nt small interfering (si)RNA or
      micro (mi)RNA by RNaseIII-like enzymes called Dicers. Gene regulations by RNA
      silencing have fundamental implications in a large number of biological processes
      that include antiviral defense, maintenance of genome integrity and the
      orchestration of cell fates. Although most generic or core components of the
      various plant small RNA pathways have been likely identified over the past 15
      years, factors involved in RNAi regulation through post-translational
      modifications are just starting to emerge, mostly through forward genetic
      studies. A genetic screen designed to identify factors required for RNAi in
      Arabidopsis identified the serine/threonine protein kinase, TOUSLED (TSL).
      Mutations in TSL affect exogenous and virus-derived siRNA activity in a manner
      dependent upon its kinase activity. By contrast, despite their pleiotropic
      developmental phenotype, tsl mutants show no defect in biogenesis or activity of
      miRNA or endogenous trans-acting siRNA. These data suggest a possible role for
      TSL phosphorylation in the specific regulation of exogenous and antiviral RNA
      silencing in Arabidopsis and identify TSL as an intrinsic regulator of RNA
      interference. 

PMID- 24920831
TI  - Detection and characterization of spacer integration intermediates in type I-E
      CRISPR-Cas system.
AB  - The adaptation against foreign nucleic acids by the CRISPR-Cas system (Clustered
      Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins)
      depends on the insertion of foreign nucleic acid-derived sequences into the
      CRISPR array as novel spacers by still unknown mechanism. We identified and
      characterized in Escherichia coli intermediate states of spacer integration and
      mapped the integration site at the chromosomal CRISPR array in vivo. The results
      show that the insertion of new spacers occurs by site-specific nicking at both
      strands of the leader proximal repeat in a staggered way and is accompanied by
      joining of the resulting 5'-ends of the repeat strands with the 3'-ends of the
      incoming spacer. This concerted cleavage-ligation reaction depends on the metal
      binding center of Cas1 protein and requires the presence of Cas2. By acquisition
      assays using plasmid-located CRISPR array with mutated repeat sequences, we
      demonstrate that the primary sequence of the first repeat is crucial for cleavage
      of the CRISPR array and the ligation of new spacer DNA. 

PMID- 24920833
TI  - Metabolic suppression in mammalian hibernation: the role of mitochondria.
AB  - Hibernation evolved in some small mammals that live in cold environments,
      presumably to conserve energy when food supplies are low. Throughout the winter,
      hibernators cycle spontaneously between torpor, with low metabolism and near
      freezing body temperatures, and euthermia, with high metabolism and body
      temperatures near 37 degrees C. Understanding the mechanisms underlying this
      natural model of extreme metabolic plasticity is important for fundamental and
      applied science. During entrance into torpor, reductions in metabolic rate begin
      before body temperatures fall, even when thermogenesis is not active, suggesting
      active mechanisms of metabolic suppression, rather than passive thermal effects.
      Mitochondrial respiration is suppressed during torpor, especially when measured
      in liver mitochondria fuelled with succinate at 37 degrees C in vitro. This
      suppression of mitochondrial metabolism appears to be invoked quickly during
      entrance into torpor when body temperature is high, but is reversed slowly during
      arousal when body temperature is low. This pattern may reflect body temperature
      sensitive, enzyme-mediated post-translational modifications of oxidative
      phosphorylation complexes, for instance by phosphorylation or acetylation. 

PMID- 24920832
TI  - GtrS and GltR form a two-component system: the central role of 2-ketogluconate in
      the expression of exotoxin A and glucose catabolic enzymes in Pseudomonas
      aeruginosa.
AB  - In the human pathogen Pseudomonas aeruginosa, the GltR regulator is required for
      glucose transport, whereas GtrS is a sensor kinase that plays a key role in
      mediating bacteria-host interaction and pathogen dissemination in the host. We
      show that GtrS and GltR form a two-component system that regulates the expression
      from the promoters Pedd/gap-1, PoprB and Pglk, which control the expression of
      genes involved in glucose metabolism and transport. In addition, the GtrS/GltR
      pair regulates the expression of toxA that encodes exotoxin A, the primary
      virulence factor. Microcalorimetry-based ligand screening of the recombinant GtrS
      ligand-binding domain revealed specific binding of 2-ketogluconate (2-KG) (KD=5
      MUM) and 6-phosphogluconate (KD=98 MUM). These effectors accelerate GtrS
      autophosphorylation, with concomitant transphosphorylation of GltR leading to a
      three-fold increase in transcription. Surprisingly, in vivo a similar increase in
      expression from the above promoters was observed for the mutant deficient in GltR
      regardless of the presence of effectors. The GltR operator site was found to
      contain the consensus sequence 5'-tgGTTTTTc-3'. We propose that 2-KG is a key
      metabolite in the stringent transcriptional control of genes involved in
      virulence and glucose metabolism. We show that GltR is a transcriptional
      repressor that is released from DNA upon phosphorylation.

PMID- 24920834
TI  - Energetic demands of immature sea otters from birth to weaning: implications for
      maternal costs, reproductive behavior and population-level trends.
AB  - Sea otters (Enhydra lutris) have the highest mass-specific metabolic rate of any
      marine mammal, which is superimposed on the inherently high costs of reproduction
      and lactation in adult females. These combined energetic demands have been
      implicated in the poor body condition and increased mortality of female sea
      otters nearing the end of lactation along the central California coast. However,
      the cost of lactation is unknown and currently cannot be directly measured for
      this marine species in the wild. Here, we quantified the energetic demands of
      immature sea otters across five developmental stages as a means of assessing the
      underlying energetic challenges associated with pup rearing that may contribute
      to poor maternal condition. Activity-specific metabolic rates, daily activity
      budgets and field metabolic rates (FMR) were determined for each developmental
      stage. Mean FMR of pre-molt pups was 2.29 +/- 0.81 MJ day(-1) and increased to
      6.16 +/- 2.46 and 7.41 +/- 3.17 MJ day(-1) in post-molt pups and dependent
      immature animals, respectively. Consequently, daily energy demands of adult
      females increase 17% by 3 weeks postpartum and continue increasing to 96% above
      pre-pregnancy levels by the average age of weaning. Our results suggest that the
      energetics of pup rearing superimposed on small body size, marine living and
      limited on-board energetic reserves conspire to make female sea otters
      exceptionally vulnerable to energetic shortfalls. By controlling individual
      fitness, maternal behavior and pup provisioning strategies, this underlying
      metabolic challenge appears to be a major factor influencing current population
      trends in southern sea otters (Enhydra lutris nereis).

PMID- 24920835
TI  - Generalization and discrimination tasks yield concordant measures of perceived
      distance between odours and their binary mixtures in larval Drosophila.
AB  - Similarity between odours is notoriously difficult to measure. Widely used
      behavioural approaches in insect olfaction research are cross-adaptation,
      masking, as well as associative tasks based on olfactory learning and the
      subsequent testing for how specific the established memory is. A concern with
      such memory-based approaches is that the learning process required to establish
      an odour memory may alter the way the odour is processed, such that measures of
      perception taken at the test are distorted. The present study was therefore
      designed to see whether behavioural judgements of perceptual distance are
      different for two different memory-based tasks, namely generalization and
      discrimination. We used odour-reward learning in larval Drosophila as a study
      case. In order to challenge the larvae's olfactory system, we chose to work with
      binary mixtures and their elements (1-octanol, n-amyl acetate, 3-octanol,
      benzaldehyde and hexyl acetate). We determined the perceptual distance between
      each mixture and its elements, first in a generalization task, and then in a
      discrimination task. It turns out that scores of perceptual distance are
      correlated between both tasks. A re-analysis of published studies looking at
      element-to-element perceptual distances in larval reward learning and in adult
      punishment learning confirms this result. We therefore suggest that across a
      given set of olfactory stimuli, associative training does not grossly alter the
      pattern of perceptual distances. 

PMID- 24920836
TI  - Fire ants actively control spacing and orientation within self-assemblages.
AB  - To overcome obstacles and survive harsh environments, fire ants link their bodies
      together to form self-assemblages such as rafts, bridges and bivouacs. Such
      structures are examples of self-assembling and self-healing materials, as ants
      can quickly create and break links with one another in response to changes in
      their environment. Because ants are opaque, the arrangement of the ants within
      these three-dimensional networks was previously unknown. In this experimental
      study, we applied micro-scale computed tomography, or micro-CT, to visualize the
      connectivity, arrangement and orientation of ants within an assemblage. We
      identified active and geometric mechanisms that ants use to obtain favorable
      packing properties with respect to well-studied packing of inert objects such as
      cylinders. Ants use their legs to push against their neighbors, doubling their
      spacing relative to random packing of cylinders. These legs also permit active
      control of their orientation, an ability ants use to arrange themselves
      perpendicularly rather than in parallel. Lastly, we found an important role of
      ant polymorphism in promoting self-aggregation: a large distribution of ant sizes
      permits small ants to fit between the legs of larger ants, a phenomenon that
      increases the number of average connections per ant. These combined mechanisms
      lead to low packing fraction and high connectivity, which increase raft buoyancy
      and strength during flash floods. 

PMID- 24920837
TI  - Paradox of the drinking-straw model of the butterfly proboscis.
AB  - Fluid-feeding Lepidoptera use an elongated proboscis, conventionally modeled as a
      drinking straw, to feed from pools and films of liquid. Using the monarch
      butterfly, Danaus plexippus (Linnaeus), we show that the inherent structural
      features of the lepidopteran proboscis contradict the basic assumptions of the
      drinking-straw model. By experimentally characterizing permeability and flow in
      the proboscis, we show that tapering of the food canal in the drinking region
      increases resistance, significantly hindering the flow of fluid. The calculated
      pressure differential required for a suction pump to support flow along the
      entire proboscis is greater than 1 atm (~101 kPa) when the butterfly feeds from a
      pool of liquid. We suggest that behavioral strategies employed by butterflies and
      moths can resolve this paradoxical pressure anomaly. Butterflies can alter the
      taper, the interlegular spacing and the terminal opening of the food canal,
      thereby controlling fluid entry and flow, by splaying the galeal tips apart,
      sliding the galeae along one another, pulsing hemolymph into each galeal lumen,
      and pressing the proboscis against a substrate. Thus, although physical
      construction of the proboscis limits its mechanical capabilities, its
      functionality can be modified and enhanced by behavioral strategies. 

PMID- 24920838
TI  - Water surface locomotion in tropical canopy ants.
AB  - Upon falling onto the water surface, most terrestrial arthropods helplessly
      struggle and are quickly eaten by aquatic predators. Exceptions to this outcome
      mostly occur among riparian taxa that escape by walking or swimming at the water
      surface. Here we document sustained, directional, neustonic locomotion (i.e.
      surface swimming) in tropical arboreal ants. We dropped 35 species of ants into
      natural and artificial aquatic settings in Peru and Panama to assess their
      swimming ability. Ten species showed directed surface swimming at speeds >3 body
      lengths s(-1), with some swimming at absolute speeds >10 cm s(-1). Ten other
      species exhibited partial swimming ability characterized by relatively slow but
      directed movement. The remaining species showed no locomotory control at the
      surface. The phylogenetic distribution of swimming among ant genera indicates
      parallel evolution and a trend toward negative association with directed aerial
      descent behavior. Experiments with workers of Odontomachus bauri showed that they
      escape from the water by directing their swimming toward dark emergent objects
      (i.e. skototaxis). Analyses of high-speed video images indicate that Pachycondyla
      spp. and O. bauri use a modified alternating tripod gait when swimming; they
      generate thrust at the water surface via synchronized treading and rowing motions
      of the contralateral fore and mid legs, respectively, while the hind legs provide
      roll stability. These results expand the list of facultatively neustonic
      terrestrial taxa to include various species of tropical arboreal ants. 

PMID- 24920841
TI  - Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors
      for response, long-term outcomes and tolerance.
AB  - BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid
      sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and
      calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of
      rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and
      safe alternative in childhood. METHODS: Because data from adults remain sparse,
      we conducted a large retrospective and multicentric study that included 41 adults
      with MCNS and receiving RTX. RESULTS: Complete (NS remission and withdrawal of
      all immunosuppressants) and partial (NS remission and withdrawal of at least one
      immunosuppressants) clinical responses were obtained for 25 and 7 patients,
      respectively (overall response 78%), including 3 patients that only received RTX
      and had a complete clinical response. After a follow-up time of 39 months (6-71),
      relapses occurred in 18 responder patients [56%, median time 18 months (3-36)].
      Seventeen of these received a second course of RTX and then had a complete (n =
      13) or partial (n = 4) clinical response. From multivariate analysis, on-going
      mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive
      factor for RTX failure [HR = 0.07 95% CI (0.01-0.04), P = 0.003]. Interestingly,
      nine patients were still in remission at 14 months (3-36) after B-cell recovery.
      No significant early or late adverse event occurred after RTX therapy.
      CONCLUSIONS: RTX is safe and effective in adult patients with MCNS and could be
      an alternative to steroids or CNIs in patients with a long history of relapsing
      MCNS.

PMID- 24920842
TI  - A new clinical multivariable model that predicts postoperative acute kidney
      injury: impact of endogenous ouabain.
AB  - BACKGROUND: Acute kidney injury (AKI) is an important complication of cardiac
      surgery. Recently, elevated levels of endogenous ouabain (EO), an adrenal stress
      hormone with haemodynamic and renal effects, have been associated with worse
      renal outcome after cardiac surgery. Our aim was to develop and evaluate a new
      risk model of AKI using simple preoperative clinical parameters and to
      investigate the utility of EO. METHODS: The primary outcome was AKI according to
      Acute Kidney Injury Network stage II or III. We selected the Northern New England
      Cardiovascular Disease Study Group (NNECDSG) as a reference model. We built a new
      internal predictive risk model considering common clinical variables (CLIN-RISK),
      compared this model with the NNECDSG model and determined whether the addition of
      preoperative plasma EO improved prediction of AKI. RESULTS: All models were
      tested on >800 patients admitted for elective cardiac surgery in our hospital.
      Seventy-nine patients developed AKI (9.9%). Preoperative EO levels were strongly
      associated with the incidence of AKI and clinical complication (total ICU stay
      and in-hospital mortality). The NNECDSG model was confirmed as a good predictor
      of AKI (AUC 0.74, comparable to the NNECDSG reference population). Our CLIN-RISK
      model had improved predictive power for AKI (AUC 0.79, CI 95% 0.73-0.84).
      Furthermore, addition of preoperative EO levels to both clinical models improved
      AUC to 0.79 and to 0.83, respectively (DeltaAUC +0.05 and +0.04, respectively, P
      < 0.01). CONCLUSION: In a population where the predictive power of the NNECDSG
      model was confirmed, CLIN-RISK was more powerful. Both clinical models were
      further improved by the addition of preoperative plasma EO levels. These new
      models provide improved predictability of the relative risk for the development
      of AKI following cardiac surgery and suggest that EO is a marker for renal
      vascular injury.

PMID- 24920843
TI  - IL-17 promotes murine lupus.
AB  - The proinflammatory activity of IL-17-producing Th17 cells has been associated
      with the pathogenesis of several autoimmune diseases. In this article, we provide
      direct evidence for a role of IL-17 in the pathogenesis of systemic lupus
      erythematosus (SLE). The induction of SLE by pristane in IL-17-sufficient wild
      type mice did not occur in IL-17-deficient mice, which were protected from
      development of lupus autoantibodies and glomerulonephritis. The protection from
      SLE in IL-17-deficient mice was associated with a reduced frequency of CD3(+)CD4(
      )CD8(-) double-negative T cells and an expansion of CD4(+) regulatory T cells,
      and did not depend on Stat-1 signaling. These data affirm the key role of IL-17
      in the pathogenesis of SLE and strengthen the support for IL-17 blockade in the
      therapy of SLE. 

PMID- 24920844
TI  - Id1 expression promotes T regulatory cell differentiation by facilitating TCR
      costimulation.
AB  - T regulatory (Treg) cells play crucial roles in the regulation of cellular
      immunity. The development of Treg cells depends on signals from TCRs and IL-2Rs
      and is influenced by a variety of transcription factors. The basic helix-loop
      helix proteins are known to influence TCR signaling thresholds. Whether this
      property impacts Treg differentiation is not understood. In this study, we
      interrogated the role of basic helix-loop-helix proteins in the production of
      Treg cells using the CD4 promoter-driven Id1 transgene. We found that Treg cells
      continued to accumulate as Id1 transgenic mice aged, resulting in a significant
      increase in Treg cell counts in the thymus as well as in the periphery compared
      with wild-type controls. Data from mixed bone marrow assays suggest that Id1 acts
      intrinsically on developing Treg cells. We made a connection between Id1
      expression and CD28 costimulatory signaling because Id1 transgene expression
      facilitated the formation of Treg precursors in CD28(-/-) mice and the in vitro
      differentiation of Treg cells on thymic dendritic cells despite the blockade of
      costimulation by anti-CD80/CD86. Id1 expression also allowed in vitro Treg
      differentiation without anti-CD28 costimulation, which was at least in part due
      to enhanced production of IL-2. Notably, with full strength of costimulatory
      signals, however, Id1 expression caused modest but significant suppression of
      Treg induction. Finally, we demonstrate that Id1 transgenic mice were less
      susceptible to the induction of experimental autoimmune encephalomyelitis, thus
      illustrating the impact of Id1-mediated augmentation of Treg cell levels on
      cellular immunity. 

PMID- 24920845
TI  - Elevated levels of mast cells are involved in pruritus associated with
      polycythemia vera in JAK2V617F transgenic mice.
AB  - Pruritus occurs frequently in patients with polycythemia vera (PV), and the
      pathophysiology of PV-associated pruritus is unclear. We have previously
      demonstrated that transgenic mice expressing JAK2V617F displayed clear PV-like
      phenotypes. In the current study, we found frequent occurrence of pruritus with
      aged JAK2V617F transgenic mice and further investigated the underlying mechanisms
      by studying mast cells, key players in allergic reactions and anaphylaxis.
      Massive accumulations of mast cells were observed in the skin of pruritic
      JAK2V617F transgenic mice. In vitro culture yielded much higher mast cell counts
      from the bone marrow, spleen, peripheral blood, and peritoneal cavity of
      JAK2V617F transgenic mice than from controls. Cultured mast cells from JAK2V617F
      transgenic mice exhibited enhanced proliferative signals, relative resistance to
      cell death upon growth factor deprivation, and a growth advantage over control
      cells under suboptimal growth conditions. However, these mast cells displayed
      normal morphology and contained normal levels of mast cell proteases before and
      after degranulation. Finally, the JAK2 inhibitor G6 effectively reduced mast cell
      numbers and alleviated pruritus in JAK2V617F transgenic mice. Collectively, these
      data demonstrate that mast cells are involved in PV-associated pruritogenesis and
      that JAK2 inhibitors are potential antipruritus drugs. 

PMID- 24920847
TI  - Small strokes causing severe vertigo: frequency of false-negative MRIs and
      nonlacunar mechanisms.
AB  - OBJECTIVE: Describe characteristics of small strokes causing acute vestibular
      syndrome (AVS). METHODS: Ambispective cross-sectional study of patients with AVS
      (acute vertigo or dizziness, nystagmus, nausea/vomiting, head-motion intolerance,
      unsteady gait) with at least one stroke risk factor from 1999 to 2011 at a single
      stroke referral center. Patients underwent nonquantitative HINTS "plus"
      examination (head impulse, nystagmus, test-of-skew plus hearing), neuroimaging to
      confirm diagnoses (97% by MRI), and repeat MRI in those with initially normal
      imaging but clinical signs of a central lesion. We identified patients with
      diffusion-weighted imaging (DWI) strokes <=10 mm in axial diameter. RESULTS: Of
      190 high-risk AVS presentations (105 strokes), we found small strokes in 15
      patients (median age 64 years, range 41-85). The most common vestibular structure
      infarcted was the inferior cerebellar peduncle (73%); the most common stroke
      location was the lateral medulla (60%). Focal neurologic signs were present in
      only 27%. The HINTS "plus" battery identified small strokes with greater
      sensitivity than early MRI-DWI (100% vs 47%, p < 0.001). False-negative initial
      MRIs (6-48 hours) were more common with small strokes than large strokes (53% [n
      = 8/15] vs 7.8% [n = 7/90], p < 0.001). Nonlacunar stroke mechanisms were
      responsible in 47%, including 6 vertebral artery occlusions or dissections.
      CONCLUSIONS: Small strokes affecting central vestibular projections can present
      with isolated AVS. The HINTS "plus" hearing battery identifies these patients
      with greater accuracy than early MRI-DWI, which is falsely negative in half, up
      to 48 hours after onset. We found nonlacunar mechanisms in half, suggesting
      greater risk than might otherwise be assumed for patients with such small
      infarctions.

PMID- 24920849
TI  - Dopamine-dependent functional connectivity in Parkinson disease: a resting-state
      diagnosis?

PMID- 24920846
TI  - Cellular stress amplifies TLR3/4-induced CXCL1/2 gene transcription in
      mononuclear phagocytes via RIPK1.
AB  - The impact of environmental stressors on the magnitude of specific chemokine gene
      expression was examined in mouse bone marrow-derived macrophages stimulated
      through various TLRs. Levels of TLR-stimulated CXCL1 and CXCL2 but not CXCL10 or
      CCL5 mRNAs were selectively enhanced (>10-fold) in stressed macrophages. The
      amplification was also manifested for other proinflammatory cytokines, including
      TNF-alpha, IL-1alpha, and IL-6. Responses through TLR3 and TLR4 exhibited the
      greatest sensitivity, reflecting a requirement for Toll/IL-IR domain-containing
      adaptor-inducing IFN-beta (TRIF), the adaptor protein selectively associated with
      these TLRs. IFN regulatory factor 3, a transcription factor that is downstream of
      TLR4/TRIF signaling, was not required for sensitivity to stress-induced chemokine
      amplification. c/EBP homologous protein and X box binding protein 1 have been
      reported to enhance inflammatory cytokine responses but are not required for
      amplification of TLR3/4-induced CXCL1 expression. Rather, receptor-interacting
      protein kinase 1, a kinase also linked with TLR3/4/TRIF signaling, is required
      and involves a stress-dependent increase in its abundance and ubiquitination.
      Whereas NF-kappaB activation is necessary for TLR-induced chemokine gene
      transcription, this factor does not appear to be the primary mechanistic target
      of environmental stress. The application of stress also enhanced chemokine
      expression in macrophages infiltrating the peritoneal cavity but was not observed
      in the resident peritoneal cells or in the liver. These findings identify novel
      mechanisms for modulating the magnitude and duration of selective TLR-induced
      chemokine and cytokine gene expression and further establish the importance of
      cell stress pathways in coordinating the outcomes of cellular and tissue injury. 

PMID- 24920848
TI  - Antibodies to single glycolipids and glycolipid complexes in Guillain-Barre
      syndrome subtypes.
AB  - OBJECTIVE: To comprehensively investigate the relationship between antibodies to
      single glycolipids and their complexes and Guillain-Barre syndrome subtypes and
      clinical features. METHODS: In acute sera from 199 patients with Guillain-Barre
      syndrome, immunoglobulin G (IgG) antibodies to glycolipids and ganglioside
      complexes were tested using ELISA against individual antigens from single
      glycolipids including gangliosides (LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GD1b,
      GT1a, GT1b, GQ1b) and a neutral glycolipid, asialo-GM1 (GA1), and antigens from
      the combination of 2 different glycolipids. Based on serial nerve conduction
      studies, the electrodiagnoses were as follows: 69 demyelinating subtype, 85
      axonal subtypes, and 45 unclassified. RESULTS: Significant associations were
      detected between acute motor axonal neuropathy subtype and IgG antibodies to GM1,
      GalNAc-GD1a, GA1, or LM1/GA1 complex. Reversible conduction failure was
      significantly associated with IgG antibodies to GM1, GalNAc-GD1a, GD1b, or
      complex of LM1/GA1. No significant association was demonstrated between acute
      inflammatory demyelinating polyneuropathy and any of the glycolipids or
      ganglioside complexes. Anti-ganglioside complex antibodies alone were detected in
      7 patients (5 axonal subtype). CONCLUSIONS: The current study demonstrates that
      antibodies to single glycolipids and ganglioside complexes are associated with
      acute motor axonal neuropathy or acute motor conduction block neuropathy but not
      acute inflammatory demyelinating polyneuropathy. CLASSIFICATION OF EVIDENCE: This
      study provides Class II evidence that antibodies to glycolipids are increased in
      patients with acute motor axonal neuropathy and acute motor conduction block
      neuropathy but not acute inflammatory demyelinating polyneuropathy.

PMID- 24920851
TI  - Dietary protein and stroke prevention: is the Eskimo diet the answer to avoid
      stroke?

PMID- 24920850
TI  - Early developmental trajectories associated with ASD in infants with tuberous
      sclerosis complex.
AB  - OBJECTIVE: We performed a longitudinal cohort study of infants with tuberous
      sclerosis complex (TSC), with the overarching goal of defining early clinical,
      behavioral, and biological markers of autism spectrum disorder (ASD) in this high
      risk population. METHODS: Infants with TSC and typically developing controls were
      recruited as early as 3 months of age and followed longitudinally until 36 months
      of age. Data gathered at each time point included detailed seizure history,
      developmental testing using the Mullen Scales of Early Learning, and social
      communication assessments using the Autism Observation Scale for Infants. At 18
      to 36 months, a diagnostic evaluation for ASD was performed using the Autism
      Diagnostic Observation Schedule. RESULTS: Infants with TSC demonstrated delays
      confined to nonverbal abilities, particularly in the visual domain, which then
      generalized to more global delays by age 9 months. Twenty-two of 40 infants with
      TSC were diagnosed with ASD. Both 12-month cognitive ability and developmental
      trajectories over the second and third years of life differentiated the groups.
      By 12 months of age, the ASD group demonstrated significantly greater cognitive
      delays and a significant decline in nonverbal IQ from 12 to 36 months.
      CONCLUSIONS: This prospective study characterizes early developmental markers of
      ASD in infants with TSC. The early delay in visual reception and fine motor
      ability in the TSC group as a whole, coupled with the decline in nonverbal
      ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD
      that can inform more targeted interventions for these high-risk infants.

PMID- 24920852
TI  - B-cell depletion in children with neuroimmunologic conditions: the learning
      curve.

PMID- 24920853
TI  - Alemtuzumab and multiple sclerosis: is it safe?

PMID- 24920854
TI  - Alemtuzumab: the advantages and challenges of a novel therapy in MS.
AB  - Our understanding of the pathogenesis of multiple sclerosis has increased
      considerably, leading to the development of novel therapeutic approaches and
      compounds. Several agents have undergone clinical testing and have recently
      received market authorization or are being evaluated for approval. Alemtuzumab is
      a humanized monoclonal antibody that rapidly depletes CD52+ cells of the lymphoid
      lineage from peripheral blood, but spares lymphoid precursor cells. Clinical
      efficacy and safety data from clinical phase II and III trials-all using
      interferon-beta-1a as active comparator-are summarized and placed in perspective.
      This review further analyzes the differential reconstitution of T and B cells as
      a potential mode of action and the pathogenic link to treatment-emergent
      secondary autoimmune conditions. Given recent positive opinions by regulatory
      agencies, this new drug will be positioned for the treatment of active relapsing
      remitting multiple sclerosis and enlarge our therapeutic armamentarium. 

PMID- 24920855
TI  - Quantitative analysis of dietary protein intake and stroke risk.
AB  - OBJECTIVE: To perform a meta-analysis of prospective studies to evaluate the
      relation between dietary protein intake and stroke risk. METHODS: Relevant
      studies were identified by searching PubMed and Embase through November 2013, and
      by reviewing the reference lists of retrieved articles. We included prospective
      cohort studies that reported relative risks (RRs) with 95% confidence intervals
      (CIs) for the association between dietary protein intake and stroke risk.
      RESULTS: The meta-analysis included 7 prospective studies involving 254,489
      participants. The pooled RR of stroke for the highest compared with the lowest
      dietary protein intake was 0.80 (95% CI 0.66-0.99). Dose-response analysis
      indicated that a 20-g/d increment in dietary protein intake was associated with a
      26% reduction in stroke risk. Stratifying by protein type, the RR of stroke for
      animal protein was 0.71 (95% CI 0.50-0.99). Sensitivity analysis restricted to
      studies with control for common risk factors yielded similar results, and
      omission of any single study did not change the overall result. CONCLUSION: These
      findings suggest that moderate dietary protein intake may lower the risk of
      stroke.

PMID- 24920856
TI  - Functional connectivity in the basal ganglia network differentiates PD patients
      from controls.
AB  - OBJECTIVE: To examine functional connectivity within the basal ganglia network
      (BGN) in a group of cognitively normal patients with early Parkinson disease (PD)
      on and off medication compared to age- and sex-matched healthy controls (HC), and
      to validate the findings in a separate cohort of participants with PD. METHODS:
      Participants were scanned with resting-state fMRI (RS-fMRI) at 3T field strength.
      Resting-state networks were isolated using independent component analysis. A BGN
      template was derived from 80 elderly HC participants. BGN maps were compared
      between 19 patients with PD on and off medication in the discovery group and 19
      age- and sex-matched controls to identify a threshold for optimal group
      separation. The threshold was applied to 13 patients with PD (including 5 drug
      naive) in the validation group to establish reproducibility of findings. RESULTS:
      Participants with PD showed reduced functional connectivity with the BGN in a
      wide range of areas. Administration of medication significantly improved
      connectivity. Average BGN connectivity differentiated participants with PD from
      controls with 100% sensitivity and 89.5% specificity. The connectivity threshold
      was tested on the validation cohort and achieved 85% accuracy. CONCLUSIONS: We
      demonstrate that resting functional connectivity, measured with MRI using an
      observer-independent method, is reproducibly reduced in the BGN in cognitively
      intact patients with PD, and increases upon administration of dopaminergic
      medication. Our results hold promise for RS-fMRI connectivity as a biomarker in
      early PD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that
      average connectivity in the BGN as measured by RS-fMRI distinguishes patients
      with PD from age- and sex-matched controls.

PMID- 24920857
TI  - Microinfarct disruption of white matter structure: a longitudinal diffusion
      tensor analysis.
AB  - OBJECTIVE: To evaluate the local effect of small asymptomatic infarctions
      detected by diffusion-weighted imaging (DWI) on white matter microstructure using
      longitudinal structural and diffusion tensor imaging (DTI). METHODS: Nine acute
      to subacute DWI lesions were identified in 6 subjects with probable cerebral
      amyloid angiopathy who had undergone high-resolution MRI both before and after
      DWI lesion detection. Regions of interest (ROIs) corresponding to the site of the
      DWI lesion (lesion ROI) and corresponding site in the nonlesioned contralateral
      hemisphere (control ROI) were coregistered to the pre- and postlesional scans.
      DTI tractography was additionally performed to reconstruct the white matter
      tracts containing the ROIs. DTI parameters (fractional anisotropy [FA], mean
      diffusivity [MD]) were quantified within each ROI, the 6-mm lesion-containing
      tract segments, and the entire lesion-containing tract bundle. Lesion/control FA
      and MD ratios were compared across time points. RESULTS: The postlesional scans
      (performed a mean 7.1 +/- 4.7 months after DWI lesion detection) demonstrated a
      decrease in median FA lesion/control ROI ratio (1.08 to 0.93, p = 0.038) and
      increase in median MD lesion/control ROI ratio (0.97 to 1.17, p = 0.015) relative
      to the prelesional scans. There were no visible changes on postlesional high
      resolution T1-weighted and fluid-attenuated inversion recovery images in 4 of 9
      lesion ROIs and small (2-5 mm) T1 hypointensities in the remaining 5. No
      postlesional changes in FA or MD ratios were detected in the 6-mm lesion
      containing tract segments or full tract bundles. CONCLUSIONS: Asymptomatic DWI
      lesions produce chronic local microstructural injury. The cumulative effects of
      these widely distributed lesions may directly contribute to small-vessel-related
      vascular cognitive impairment.

PMID- 24920859
TI  - Ranvier revisited: novel nodal antigens stimulate interest in GBS pathogenesis.

PMID- 24920858
TI  - Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre
      syndrome.
AB  - OBJECTIVE: Previous histochemical studies in the demyelinating form of Guillain
      Barre syndrome (GBS), acute inflammatory demyelinating polyneuropathy (AIDP),
      have shown complement deposition on the surface of Schwann cells, and therefore
      unknown epitopes would be present on the outer surface of Schwann cells. METHODS:
      We used a proteomic-based approach to search for the target molecules of AIDP in
      the extracted proteins from schwannoma cells. Sera were obtained from 40 patients
      with GBS, 31 controls with inflammatory disease, and 46 normal controls. RESULTS:
      We found that patients with AIDP after cytomegalovirus (CMV) infection have serum
      autoantibodies against membrane-organizing extension spike protein (moesin),
      which is expressed in the Schwann cell processes at the nodes of Ranvier and is
      crucial for myelination. Of the 40 patients with GBS, 6 had recent CMV infection
      and 5 of them (83%) had high levels of serum immunoglobulin G antibodies against
      moesin. The anti-moesin antibodies were found in none of the control subjects
      with disease including 5 with CMV infection but no neuropathy, and only 2 (4%) of
      the 46 normal control subjects. Immunocytochemistry showed that moesin was
      stained at the distal tips of schwannoma cells by sera from the patients with CMV
      related AIDP but not by sera from controls. CONCLUSION: Moesin is a possible
      immunologic target molecule of pathogenic autoantibodies in patients with CMV
      related AIDP. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence
      that levels of serum anti-moesin antibodies accurately distinguishes CMV-related
      AIDP from non-CMV-related AIDP (sensitivity 83%, specificity 93%).

PMID- 24920860
TI  - Comment: EEGs not likely helpful for behavioral assessments in Smith-Lemli-Opitz.

PMID- 24920863
TI  - The DNA Data Deluge: Fast, efficient genome sequencing machines are spewing out
      more data than geneticists can analyze.

PMID- 24920861
TI  - Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS
      disease.
AB  - OBJECTIVE: To assess the utility and safety of rituximab in pediatric autoimmune
      and inflammatory disorders of the CNS. METHODS: Multicenter retrospective study.
      RESULTS: A total of 144 children and adolescents (median age 8 years, range 0.7
      17; 103 female) with NMDA receptor (NMDAR) encephalitis (n = 39), opsoclonus
      myoclonus ataxia syndrome (n = 32), neuromyelitis optica spectrum disorders (n =
      20), neuropsychiatric systemic lupus erythematosus (n = 18), and other
      neuroinflammatory disorders (n = 35) were studied. Rituximab was given after a
      median duration of disease of 0.5 years (range 0.05-9.5 years). Infusion adverse
      events were recorded in 18/144 (12.5%), including grade 4 (anaphylaxis) in 3.
      Eleven patients (7.6%) had an infectious adverse event (AE), including 2 with
      grade 5 (death) and 2 with grade 4 (disabling) infectious AE (median follow-up of
      1.65 years [range 0.1-8.5]). No patients developed progressive multifocal
      leukoencephalopathy. A definite, probable, or possible benefit was reported in
      125 of 144 (87%) patients. A total of 17.4% of patients had a modified Rankin
      Scale (mRS) score of 0-2 at rituximab initiation, compared to 73.9% at outcome.
      The change in mRS 0-2 was greater in patients given rituximab early in their
      disease course compared to those treated later. CONCLUSION: While limited by the
      retrospective nature of this analysis, our data support an off-label use of
      rituximab, although the significant risk of infectious complications suggests
      rituximab should be restricted to disorders with significant morbidity and
      mortality. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that
      in pediatric autoimmune and inflammatory CNS disorders, rituximab improves
      neurologic outcomes with a 7.6% risk of adverse infections.

PMID- 24920862
TI  - Variations in EEG discharges predict ADHD severity within individual Smith-Lemli
      Opitz patients.
AB  - OBJECTIVE: We sought to examine the prevalence of EEG abnormalities in Smith
      Lemli-Opitz syndrome (SLOS) as well as the relationship between interictal
      epileptiform discharges (IEDs) and within-subject variations in attentional
      symptom severity. METHODS: In the context of a clinical trial for SLOS, we
      performed cross-sectional and repeated-measure observational studies of the
      relationship between EEG findings and cognitive/behavioral factors on 23 children
      (aged 4-17 years). EEGs were reviewed for clinical abnormalities, including IEDs,
      by readers blinded to participants' behavioral symptoms. Between-group
      differences in baseline characteristics of participants with and without IEDs
      were analyzed. Within-subject analyses examined the association between the
      presence of IEDs and changes in attention-deficit/hyperactivity disorder (ADHD)
      symptoms. RESULTS: Of 85 EEGs, 43 (51%) were abnormal, predominantly because of
      IEDs. Only one subject had documented clinical seizures. IEDs clustered in 13
      subjects (57%), whereas 9 subjects (39%) had EEGs consistently free of IEDs.
      While there were no significant group differences in sex, age, intellectual
      disability, language level, or baseline ADHD symptoms, autistic symptoms tended
      to be more prevalent in the "IED" group (according to Autism Diagnostic
      Observation Schedule-2 criteria). Within individuals, the presence of IEDs on a
      particular EEG predicted, on average, a 27% increase in ADHD symptom severity.
      CONCLUSIONS: Epileptiform discharges are common in SLOS, despite a relatively low
      prevalence of epilepsy. Fluctuations in the presence of epileptiform discharges
      within individual children with a developmental disability syndrome may be
      associated with fluctuations in ADHD symptomatology, even in the absence of
      clinical seizures.

PMID- 24920864
TI  - Reflections on the Dimensions of Segregation.

PMID- 24920865
TI  - Tracking the Evil Eye: Trait Anger and Selective Attention within Ambiguously
      Hostile Scenes.
AB  - Previous research has shown that trait anger is associated with biases in
      attention and interpretation, but the temporal relation between these two types
      of biases remains unresolved. Indeed, two very different models can be derived
      from the literature. One model proposes that interpretation biases emerge from
      earlier biases in attention, whereas the other model proposes that hostile
      interpretations occur quickly, even prior to the allocation of attention to
      specific cues. Within the context of integrated visual scenes of ambiguously
      intended harm, the two models make opposite predictions that can be examined
      using an eye-tracking methodology. The present study (N = 45) therefore tracked
      participants' allocation of attention to hostile and non-hostile cues in
      ambiguous visual scenes, and found support for the idea that high anger
      individuals make early hostile interpretations prior to encoding hostile and non
      hostiles cues. The data are important in understanding associations between trait
      anger and cognitive biases.

PMID- 24920866
TI  - Parameter estimation in stochastic chemical kinetic models using derivative free
      optimization and bootstrapping.
AB  - Recent years have seen increasing popularity of stochastic chemical kinetic
      models due to their ability to explain and model several critical biological
      phenomena. Several developments in high resolution fluorescence microscopy have
      enabled researchers to obtain protein and mRNA data on the single cell level. The
      availability of these data along with the knowledge that the system is governed
      by a stochastic chemical kinetic model leads to the problem of parameter
      estimation. This paper develops a new method of parameter estimation for
      stochastic chemical kinetic models. There are three components of the new method.
      First, we propose a new expression for likelihood of the experimental data.
      Second, we use sample path optimization along with UOBYQA-Fit, a variant of of
      Powell's unconstrained optimization by quadratic approximation, for optimization.
      Third, we use a variant of Efron's percentile bootstrapping method to estimate
      the confidence regions for the parameter estimates. We apply the parameter
      estimation method in an RNA dynamics model of E. coli. We test the parameter
      estimates obtained and the confidence regions in this model. The testing of the
      parameter estimation method demonstrates the efficiency, reliability, and
      accuracy of the new method.

PMID- 24920867
TI  - The Use of Europiumstearate to Trace Polyethylene Wear Debris in Joint Fluid
      after Prosthetic Joint Replacement - A Feasibility Study.
AB  - Ultra-high molecular weight polyethylene (UHMWPE) is the most common counterface
      material against metals or ceramics in artificial hip or knee joints. Wear and
      the resulting particulate debris, however, limit the life span of the implant. In
      this study, the general feasibility of using Europium (Eu) as tracer material to
      quantify UHMWPE wear in joint fluid is investigated. Using Inductively Coupled
      Mass Spectrometry (ICP-MS), recovery experiments of Eu in artificial joint fluid
      were performed. In order to dope polyethylene with 50 ppm Eu, nascent UHMWPE
      powder was mixed with a solution of Eu-stearate. The heterogeneity of the mixture
      was assessed by determining the coefficient of variation (CV) of the Eu content
      in various weighted samples. After molding of the UHMWPE powder mixture,
      cylindrical pins of 10 mm diameter were machined and worn against cobalt-chromium
      metal disks submersed in artificial joint fluid. The Eu-content of fluid samples
      taken at certain time intervals was measured and compared with UHMWPE weight loss
      of the pins. A satisfactory homogenization of Eu in the UHMWPE powder was
      achieved. Tracer-based and weight-loss determined wear rates were highly
      correlated (Pearson correlation coefficients > 0.991). Also the detection bias
      was within acceptable limits. Thus both methods demonstrated good agreement.

PMID- 24920868
TI  - DF-4 Lead Connector: Innovative Technology, Unexpected Problems and Novel
      Solutions.

PMID- 24920869
TI  - Extensive Thrombosis Following Lead Extraction: Further Justification for Routine
      Post-operative Anticoagulation.
AB  - Lead extraction is becoming increasingly common as indications for pacing and ICD
      insertion expand. Periop management varies between extraction centers, and no
      clinical guidelines have addressed the need for perioperative anticoagulation. We
      report a case of massive thrombosis which occurred shortly after laser lead
      extraction and is undoubtedly related to the trauma of the extraction and ensuing
      hypercoagulabiilty. Routine post-operative anticoagulation has been advocated as
      a means to prevent access vein (subclavian) stenosis, but many centres do not
      employ a routine post-extraction anticoagulation strategy. Pulmonary embolism
      following lead extraction is a known complication of this procedure and late
      mortality following lead extraction is a significant and underappreciated
      problem. We propose that further research attention should be directed at
      addressing the issue of routine post-extraction anticoagulation. 

PMID- 24920870
TI  - A Novel Solution for the High Defibrillation Threshold in Patients with a DF-4
      Lead: Adding a High Voltage Adaptor/Splitter.
AB  - A high defibrillation threshold occurs in approximately 6% of implants. The
      defibrillation threshold can be improved by addition of a defibrillation lead.
      However, the DF-4 high energy ICD header precludes the addition of a
      defibrillation lead. Here we report on use of a new high voltage adaptor/splitter
      that enables the addition of an extra defibrillation lead. 

PMID- 24920871
TI  - Left and Right Ventricle Leads Switch as a Solution for TWave Oversensing - How a
      Good Idea Turned Out Bad.
AB  - A 50-year-old male with a CRT defibrillator received inappropriate ICD shocks due
      to T-wave oversensing. Decreasing the sensitivity to avoid T wave oversensing was
      not an option due to a suboptimal R-wave sensing amplitude. We decided to re-plug
      the LV lead in the RV port and the RV lead in the LV port. This however led to
      intermittent phrenic nerve stimulation due to mandatory bipolar (tip-ring) or
      unipolar (tip-can) pacing on the LV-lead from the RV port. Re-intervention was
      necessary with the implantation of an additional pacing/sensing RV lead. A
      software programmable choice to switch sensing and tachycardia detection from RV
      to LV lead could be a valuable feature in future CRT devices. 

PMID- 24920872
TI  - Inappropriate Detection of a Supraventricular Tachycardia as Dual Tachycardia by
      the PR LogicTM Algorithm.
AB  - Tachycardia detection and therapy algorithms in Implantable Cardioverter
      Defibrillators (ICD) reduce, but do not eliminate inappropriate ICD shocks.
      Awareness of the pros and cons of a particular algorithm helps to predict its
      utility in specific situations. We report a case where PR logicTM, an algorithm
      commonly used in currently implanted ICDs to differentiate supraventricular
      tachycardia (SVT) from ventricular tachycardia resulted in inappropriate
      detection and shock for an SVT, and discuss several solutions to the problem. 

PMID- 24920873
TI  - CRT-D Implantation Through a Persistent Left Superior Vena Cava.

PMID- 24920874
TI  - Magnetic Resonance Imaging of Stroke in the Rat.
AB  - Magnetic resonance imaging (MRI) is now a routine neuroimaging tool in the
      clinic. Throughout all phases of stroke from acute to chronic, MRI plays an
      important role to diagnose, evaluate and monitor the cerebral tissue undergoing
      stroke. This review provides a description of various MRI methods and an overview
      of selected MRI studies, with an embolic stroke model of rat, performed in the
      MRI laboratory of Department of Neurology, Henry Ford Hospital, Detroit,
      Michigan, US.

PMID- 24920875
TI  - Fixed and Random Effects Selection by REML and Pathwise Coordinate Optimization.
AB  - We propose a two-stage model selection procedure for the linear mixed-effects
      models. The procedure consists of two steps: First, penalized restricted log
      likelihood is used to select the random effects, and this is done by adopting a
      Newton-type algorithm. Next, the penalized log-likelihood is used to select the
      fixed effects via pathwise coordinate optimization to improve the computation
      efficiency. We prove that our procedure has the oracle properties. Both
      simulation studies and a real data example are carried out to examine finite
      sample performance of the proposed fixed and random effects selection procedure.
      Supplementary materials including R code used in this article and proofs for the
      theorems are available online.

PMID- 24920876
TI  - The role of stigma and uncertainty in moderating the effect of procedural justice
      on cooperation and resistance in police encounters with persons with mental
      illnesses.
AB  - Within social psychology, procedural justice theory has been used to understand
      variations in compliance with legal authorities such as police. Thus, it may help
      explain variation in cooperation and compliance in encounters between police
      officers and people with serious mental illness (SMI), which are often fraught
      with difficulty and risk. In this paper, we examine the extent to which
      perceptions of procedural justice among persons with SMI are associated with self
      reported levels of cooperation and resistance in encounters with police. We also
      examine stigma and encounter type as potential moderators of the procedural
      justice effect. 154 persons with serious mental illness who reported a police
      contact within the past year were interviewed using the newly developed Police
      Contact Experience Survey (PCES), which includes questions about the
      characteristics of the contact, perceived procedural justice (PPJ) and degree of
      cooperation and resistance. Participants also completed the Link Perceived
      Devaluation and Discrimination Scale (PDS). Findings suggest that greater PPJ is
      associated with more cooperation and less resistance. The effect on cooperation,
      however, is moderated by both perceived stigma and the type of encounter. The
      direct effect of perceived stigma (PDS) on cooperation was unexpected, with
      higher perceived stigma associated with greater cooperation. Findings underline
      the importance of both procedurally just treatment in police interactions with
      vulnerable individuals and further efforts to reduce the stigma of mental
      illness.

PMID- 24920877
TI  - Inferior Mesenteric Artery Stenting as a Novel Treatment for Chronic Mesenteric
      Ischemia in Patients with an Occluded Superior Mesenteric Artery and Celiac
      Trunk.
AB  - INTRODUCTION: Chronic mesenteric ischemia (CMI) is a challenging problem, with
      revascularization the mainstay of treatment. Management of CMI is especially
      challenging in the patient with superior mesenteric artery (SMA) and celiac
      artery (CA) occlusions. REPORT: We report a case series of four patients with
      chronic mesenteric ischemia who were not candidates for CA or SMA
      revascularization who were successfully treated with inferior mesenteric artery
      (IMA) angioplasty and stent placement to improve collateral circulation and
      palliate symptoms. DISCUSSION: To our knowledge, this is the largest case series
      to date reporting the use of an IMA stent to improve collateral circulation in
      patients with CMI.

PMID- 24920878
TI  - Role of argon laser as an adjunctive therapy for treatment of resistant infected
      corneal ulcers.
AB  - PURPOSE: To evaluate the role of argon laser as an adjunctive therapy in ten
      patients with resistant infected corneal ulcers with or without hypopyon.
      METHODS: The study included 20 patients, split into two groups of ten, with
      resistant infected corneal ulcers with or without hypopyon. One group was
      considered as the control group and treated with local and systemic specific
      antimicrobial drugs guided with culture and sensitivity tests. The other group
      started with the same specific therapy as the control group for 1 week with no
      obvious improvement and then was further treated with argon laser. The ten
      patients in the control group included five cases of fungal ulcers, three mixed
      (fungal and bacterial) ulcers, and two viral ulcers. The ten patients in the
      other group included three cases of fungal ulcers, three mixed (fungal and viral)
      ulcers, three viral ulcers, and one bacterial ulcer as proven with microbial
      culture and sensitivity tests. Eight cases of the control group and seven cases
      of the other group were associated with hypopyon. Before laser treatment, a drop
      of benoxinate hydrochloride 0.4% and a single drop of fluorescein sodium 0.25%
      were instilled. Argon laser irradiation of the affected cornea was performed
      using an argon 532 nm wavelength (Carl Zeiss LSL 532s AG; Carl Zeiss Meditec AG,
      Jena, Germany). A spot size of 500 MUm, pulse duration of 0.2 seconds, and power
      of 900 mW were used. All cases were followed up for 3 months after healing was
      achieved. RESULTS: During the first 4 weeks after laser treatment, all patients
      showed complete healing of the epithelial defect and resolution of stromal
      infiltration with no adverse effects. In the control group, four cases needed an
      amniotic membrane graft due to thinning and the other six cases were healed in a
      duration that ranged from 3 to 7 weeks. CONCLUSION: Argon laser phototherapy is
      useful as an adjunctive treatment for resistant infected corneal ulcers. More
      cases are needed to get more reliable results and to confirm our findings.

PMID- 24920879
TI  - An observational study of bimatoprost 0.01% in patients on prior intraocular
      pressure-lowering therapy: the Canadian Lumigan((r)) RC Early Analysis Review
      (CLEAR) trial.
AB  - PURPOSE: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering
      efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open
      angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical
      setting. SUBJECTS AND METHODS: This open-label, 12-week, observational study was
      conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT
      instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was
      graded by the investigator at baseline, week 6, and week 12 using a standardized
      photographic 5-point grading scale. Change in IOP from baseline was also
      evaluated at these time points. This analysis includes the subgroup of 268
      subjects who had been previously treated with latanoprost 0.005%, bimatoprost
      0.03%, travoprost 0.004%, and travoprost 0.004% with SofZiaTM or nonselective
      beta-adrenergic receptor blockers prior to the study. RESULTS: After 12 weeks of
      treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild
      hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe
      hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in
      ocular hyperemia ratings were observed at week 12 for any of the prior IOP
      lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects
      experienced an improvement. The mean percentage change from baseline IOP at week
      12 following the switch to bimatoprost 0.01% monotherapy ranged from -2.3%+/
      17.3% to -26.3%+/-12.4%. Furthermore, the decreased mean percentage change from
      baseline IOP was statistically significant across all prior IOP-lowering
      medications, except for bimatoprost 0.03% at the 6- and 12-week visits and
      travoprost 0.004% at the 6-week visit. CONCLUSION: This observational study
      demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT
      subjects who switched from prior IOP-lowering medication. Furthermore, a switch
      in ocular hypertensive treatment to bimatoprost 0.01% was associated with an
      additional 10%-15% reduction in IOP.

PMID- 24920880
TI  - Comparative study of Y-split recession versus bilateral medial rectus recession
      for surgical management of infantile esotropia.
AB  - AIM: This prospective study compares the results of bilateral medial rectus
      recession versus (vs) Y-split recession of medial recti techniques for surgical
      management of essential infantile esotropia. PATIENTS AND METHODS: Thirty
      patients were included in this study and had preoperative infantile esotropia
      with large angles (ie, >30 prism diopters [PD]). Patients were divided into Group
      A, which underwent bilateral medial rectus (BMR) recession and Group B, which
      underwent bilateral Y-split recession of medial recti muscles. All patients were
      subjected to complete ophthalmologic examination and met the criteria for
      inclusion in this study. The degrees of BMR recessions performed ranged from 6.0
      7.5 mm. All operations were performed under general anesthesia. Follow-up visits
      were conducted at 1 and 2 weeks, and 1, 3, and 6 months postoperatively. Rates of
      reoperation for residual esotropia and consecutive exotropia were determined.
      RESULTS: The patients' preoperative angles of deviation ranged from 30-80 PD.
      Group A consumed 57% less operative time than Group B. Immediately
      postoperatively, the Y-splitting technique showed satisfactory results (ie,
      orthotropic or residual angles <=15 PD) in 73% of patients vs 67% only for the
      BMR recession patients. By the end of six months of follow up; 13% of the BMR
      technique patients vs 27% of the Y-splitting technique patients showed negative
      change of PD but without reoperation. CONCLUSION: Our results suggest that,
      although the Y-splitting technique is more difficult and time consuming, both
      procedures are effective and have shown comparable results for the correction of
      horizontal deviation <=70 PD.

PMID- 24920881
TI  - Spontaneous simultaneous bilateral malignant glaucoma of a patient with no
      antecedent history of medical or surgical eye diseases.
AB  - PURPOSE: Malignant glaucoma, or aqueous misdirection syndrome, is a condition
      characterized by sudden intraocular pressure (IOP) elevation, and it is usually
      unilateral and induced by ocular surgical intervention or by medical therapy.
      Here, we report a case of simultaneous bilateral malignant glaucoma in a young
      patient with no history of any ocular diseases. CASE REPORT: A case of a 24-year
      old female with no apparent previous history of ocular medical or surgical
      conditions was referred to our hospital because of recent bilateral IOP elevation
      associated with a severe drop in vision and shallow anterior chamber with no
      posterior segment anomalies detected by ocular ultrasound in both eyes. Yttrium
      aluminum garnet (YAG) laser iridotomy dropped the IOP only temporarily and the
      patient received topical atropine treatment with combined trabeculectomy and
      anterior vitrectomy. RESULTS: In this case, the patient had a typical
      presentation of bilateral malignant glaucoma and her IOP dropped only temporarily
      following laser iridotomy to rise again shortly thereafter. Also, deepening of
      the anterior chamber and IOP decrease after topical atropine was very supportive
      of the diagnosis of malignant glaucoma. Successful management with trabeculectomy
      and limited vitrectomy also affirmed the diagnosis of malignant glaucoma.
      CONCLUSION: This is a very rare case of bilateral malignant glaucoma in a young
      adult without any prior eye conditions; only one similar case has been reported
      in the literature. We propose our own theory regarding this simultaneous
      occurrence of the pathology based on previously published studies about the
      presence of communication between the two eyes along the cerebrospinal fluid
      pathways.

PMID- 24920882
TI  - Plasma membrane coenzyme Q: evidence for a role in autism.
AB  - BACKGROUND: The Voltage Dependent Anion Channel (VDAC) is involved in control of
      autism. Treatments, including coenzyme Q, have had some success on autism
      control. DATA SOURCES: Correlation of porin redox activity and expression of
      autism is based on extensive literature, especially studies of antibodies,
      identification of cytosolic nicotinamide adenine dinucleotide reduced (NADH)
      dehydrogenase activity in the VDAC, and evidence for extreme sensitivity of the
      dehydrogenase to a mercurial. Evidence for a coenzyme Q requirement came from
      extraction and analog inhibition of NADH ferricyanide reductase in the
      erythrocyte plasma membrane, done in 1994, and reinterpreted when it was
      identified in VDAC in 2004. The effects of ubiquinol (the QH2 - reduced form of
      coenzyme Q) in children with autism were studied. RESULTS: A new role for
      coenzyme Q in the porin channels has implications on autism. Ubiquinol, the more
      active form of coenzyme Q, produces favorable response in children with autism.
      Agents which affected electron transport in porin show parallel effects in
      autism. CONCLUSION: We propose a hypothesis that autism is controlled by a
      coenzyme Q-dependent redox system in the porin channels; this conclusion is based
      on the effects of agents that positively or negatively affect electron transport
      and the symptoms of autism. The full understanding of the mechanism of their
      control needs to be established.

PMID- 24920883
TI  - Cytoprotective effect of selective small-molecule caspase inhibitors against
      staurosporine-induced apoptosis.
AB  - Caspases are currently known as the central executioners of the apoptotic
      pathways. Inhibition of apoptosis and promotion of normal cell survival by
      caspase inhibitors would be a tremendous benefit for reducing the side effects of
      cancer therapy and for control of neurodegenerative disorders such as
      Parkinson's, Alzheimer's, and Huntington's diseases. The objective of this study
      was to discover small-molecule caspase inhibitors with which to achieve
      cytoprotective effect. We completed the high-throughput screening of Bionet's
      37,500-compound library (Key Organics Limited, Camelford, Cornwall, UK) against
      caspase-1, -3, and -9 and successfully identified 43 initial hit compounds. The
      43 hit compounds were further tested for cytoprotective activity against
      staurosporine-induced cell death in NIH3T3 cells. Nineteen compounds were found
      to have significant cytoprotective effects in cell viability assays. One of the
      compounds, RBC1023, was demonstrated to protect NIH3T3 cells from staurosporine
      induced caspase-3 cleavage and activation. RBC1023 was also shown to protect
      against staurosporine-induced impairment of mitochondrial membrane potential. DNA
      microarray analysis demonstrated that staurosporine treatment induced broad
      global gene expression alterations, and RBC1023 co-treatment significantly
      restored these changes, especially of the genes that are related to cell growth
      and survival signaling such as Egr1, Cdc25c, cdkn3, Rhob, Nek2, and Taok1.
      Collectively, RBC1023 protects NIH3T3 cells against staurosporine-induced
      apoptosis via inhibiting caspase activity, restoring mitochondrial membrane
      potential, and possibly upregulating some cell survival-related gene expressions
      and pathways. 

PMID- 24920884
TI  - Chronic obstructive pulmonary disease treated with inhaled medium- or high-dose
      corticosteroids: a prospective and randomized study focusing on clinical efficacy
      and the risk of pneumonia.
AB  - PURPOSE: Complications of pneumonia development in patients with chronic
      obstructive pulmonary disease (COPD) receiving inhaled corticosteroid (ICS)
      therapy have been documented. The aim of this study was to focus on clinical
      efficacy and the incidence of pneumonia between COPD patients receiving medium
      and high doses of ICS. PATIENTS AND METHODS: This prospective, randomized study
      included COPD patients identified from three tertiary medical centers from 2010
      to 2012. The patients were randomized into two groups: high dose (HD; fluticasone
      1,000 MUg + salmeterol 100 MUg/day) and medium dose (MD; fluticasone 500 MUg +
      salmeterol 100 MUg/day). Lung function with forced expiratory volume in 1 second
      (FEV1), forced vital capacity, and COPD-assessment test (CAT) were checked every
      2 months. The frequency of acute exacerbations and number of pneumonia events
      were measured. The duration of the study period was 1 year. RESULTS: In total,
      237 COPD patients were randomized into the two treatment arms (115 in the HD
      group, 122 in the MD group). The FEV1 level was significantly improved in the
      patients in the HD group compared with those in the MD group (HD 103.9+/-26.6 mL
      versus MD 51.4+/-19.7 mL, P<0.01) at the end of the study. CAT scores were
      markedly improved in patients using an HD compared to those using an MD (HD 13+/
      5 versus MD 16+/-7, P=0.05). There was a significant difference in the percentage
      of annual rates in acute exacerbations (HD 0.16 versus MD 0.34, P<0.01) between
      the two groups. The incidence of pneumonia was similar in the two groups (HD 0.08
      versus MD 0.10, P=0.38). CONCLUSION: COPD patients treated with high doses of ICS
      had more treatment benefits and no significant increases in the incidence in
      pneumonia. Higher-dose ICS treatment may be suitable for COPD therapy.

PMID- 24920885
TI  - Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance
      protein ABCG2: polyspecificity at B-ring position.
AB  - A series of chalcones substituted by a quinoxaline unit at the B-ring were
      synthesized and tested as inhibitors of breast cancer resistance protein-mediated
      mitoxantrone efflux. These compounds appeared more efficient than analogs
      containing other B-ring substituents such as 2-naphthyl or 3,4
      methylenedioxyphenyl while an intermediate inhibitory activity was obtained with
      a 1-naphthyl group. In all cases, two or three methoxy groups had to be present
      on the phenyl A-ring to produce a maximal inhibition. Molecular modeling
      indicated both electrostatic and steric positive contributions. A higher potency
      was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to
      the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating
      preferences among polyspecificity of inhibition. 

PMID- 24920886
TI  - Anxiolytic and antidepressant-like activities of the novel and potent non
      imidazole histamine H3 receptor antagonist ST-1283.
AB  - Previous studies have suggested a potential link between histamine H3 receptors
      (H3R) signaling and anxiolytic-like and antidepressant-like effects. The aim of
      this study was to investigate the acute effects of ST-1283, a novel H3R
      antagonist, on anxiety-related and depression-related behaviors in comparison
      with those of diazepam and fluoxetine. The effects of ST-1283 were evaluated
      using the elevated plus maze test, open field test, marbles burying test, tail
      suspension test, novelty suppressed feeding test, and forced swim test in male
      C57BL/6 mice. The results showed that, like diazepam, ST-1283 (7.5 mg/kg)
      significantly modified all the parameters observed in the elevated plus maze
      test. In addition, ST-1283 significantly increased the amount of time spent in
      the center of the arena without altering general motor activity in the open field
      test. In the same vein, ST-1283 reduced the number of buried marbles as well as
      time spent digging in the marbles burying test. The tail suspension test and
      forced swim test showed that ST-1283 was able to reduce immobility time, like the
      recognized antidepressant drug fluoxetine. In the novelty suppressed feeding
      test, treatment with ST-1283 decreased latency to feed with no effect on food
      intake in the home cage. Importantly, pretreatment with the H3R agonist R-alpha
      methylhistamine abrogated the anxiolytic and antidepressant effects of ST-1283.
      Taken together, the present series of studies demonstrates the novel effects of
      this newly synthesized H3R antagonist in a number of preclinical models of
      psychiatric disorders and highlights the histaminergic system as a potential
      therapeutic target for the treatment of anxiety-related and depression-related
      disorders.

PMID- 24920887
TI  - Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model
      of focal cerebral ischemia in rats.
AB  - Recombinant 70 kDa heat shock protein (Hsp70) is an antiapoptotic protein that
      has a cell protective activity in stress stimuli and thus could be a useful
      therapeutic agent in the management of patients with acute ischemic stroke. The
      neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored
      in a model of experimental stroke in rats. Ischemia was produced by the occlusion
      of the middle cerebral artery for 45 minutes. To assess its neuroprotective
      capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes
      prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and
      brain tissue sections were stained with 2% triphenyl tetrazolium chloride.
      Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal
      response at 2.5 mg/kg). To assess Hsp70's neurotherapeutic activity, we
      intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2
      hours and 45 minutes after ischemia). Rats were then kept alive for 72 hours. The
      ischemic region was analyzed using a high-field 11 T MRI scanner. Administration
      of the Hsp70 decreased the infarction zone in a dose-dependent manner with an
      optimal (threefold) therapeutic response at 5 mg/kg. Long-term treatment of the
      ischemic rats with Hsp70 formulated in alginate granules with retarded release of
      protein further reduced the infarct volume in the brain as well as apoptotic area
      (annexin V staining). Due to its high neurotherapeutic potential, prolonged
      delivery of Hsp70 could be useful in the management of acute ischemic stroke. 

PMID- 24920888
TI  - Patient adherence issues in the treatment of hepatitis C.
AB  - The current standard-of-care treatments for chronic hepatitis C, based on a
      bitherapy that combines peginterferon alpha-2a or -2b and ribavirin for all
      genotypes, and on a triple therapy with the addition of an antiprotease
      specifically for genotype 1, are associated with a limited adherence that
      decreases their efficacy. The main factors limiting adherence are difficulties in
      taking the treatment and side effects that worsen the quality of life of the
      patients. Programs of therapeutic education are essential to improve adherence,
      quality of life, likelihood of viral suppression, improvement of liver disease,
      and decrease of late complications. Therapeutic education should be understood as
      an acquisition of decisional, technical, and social competency with the purpose
      of making the patient able to make health choices, realize their own life plans,
      and use health care resources in the best manner. The patient should be placed in
      the center of an organization, comprising various care workers who include social
      service professionals and medical staff. For hepatitis C, therapeutic education
      may be separated into three phases: a first phase corresponding to the educative
      diagnosis; a second phase corresponding to support during treatment; and the
      third phase corresponding to support after treatment. Therapeutic education is
      performed using various instruments and methods specifically adapted to the needs
      and expectations of individual patients. Upcoming treatments for hepatitis C,
      with evidence for high efficacy, few side effects, and shorter duration, will
      certainly change the landscape of adherence and the management of therapeutic
      education. 

PMID- 24920889
TI  - The effect of medical device dose-memory functions on patients' adherence to
      treatment, confidence, and disease self-management.
AB  - BACKGROUND: Adherence to treatment is an important issue in chronic disease
      management and an indicator of patients' ability to self-manage their condition
      and treatment. Some drug-dispensing and drug-delivery devices have been designed
      to support patients' medication-taking behavior by including dose-memory and
      combined dose-memory and dose-reminder functions, which electronically store, and
      visually display dose-history information, enabling the patient to review,
      monitor, and/or be actively reminded about their medication doses. PURPOSE: This
      literature review explored the role and impact of these devices on patients'
      treatment adherence, confidence with, and self-management of their condition and
      treatment. MATERIALS AND METHODS: A search of MEDLINE, Embase, and PsycINFO was
      performed to identify articles published in English from 2003-2013 that studied
      the effect of devices with dose-memory and combined dose-memory and dose-reminder
      functions on treatment adherence and users' (patients, health care professionals
      [HCPs], and caregivers) confidence, self-management behavior, and attitudes.
      RESULTS: The database searches yielded 940 abstracts from which 13 articles met
      the inclusion criteria and were retained. Devices with dose-memory and combined
      dose-memory and dose-reminder functions were found to improve self-reported and
      electronically monitored treatment adherence in chronic conditions such as
      asthma, diabetes, and HIV. The ability of the devices to provide dose-history
      information and active medication reminders was considered valuable in disease
      management by patients, caregivers, and HCPs. The devices were found to enhance
      patients' confidence in, and motivation to manage their medication and condition,
      and help reduce forgotten or incorrect medication dosing. CONCLUSION: The
      incorporation of dose-memory and combined dose-memory and dose-reminder functions
      in drug-delivery devices can improve patients' adherence, confidence, and self
      management behavior. They can target non-intentional barriers to adherence and
      can provide a means of improving disease control and clinical outcomes, thereby
      offering clinical and economic value. This review highlights the importance of
      conducting further qualitative and quantitative research to further understand
      the value and impact of these types of devices on patients' long-term adherence
      to, and self-management of treatment.

PMID- 24920890
TI  - Pulmonary adenocarcinoma mutation profile in smokers with smoking-related
      interstitial fibrosis.
AB  - Cigarette smoking is an established cause of lung cancer. However, pulmonary
      fibrosis is also an independent risk factor for the development of lung cancer.
      Smoking-related interstitial fibrosis (SRIF) has recently been reported. We
      hypothesized that adenocarcinomas in lungs with SRIF might show distinct
      molecular changes and examined the molecular phenotype of 168 resected lung
      adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was
      determined by histological examination, based on the presence of alveolar septal
      thickening, due to pauci-inflamed, hyalinized, "ropy" collagen, in areas of lung
      greater than 1 cm away from the tumor. Tumors were concomitantly examined
      genotypically for mutations in genes frequently altered in cancer, including EGFR
      and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK
      rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36)
      and/or MET amplification (n=31) were performed when no mutation was identified by
      either SNaPshot or ALK analysis. Sixty-five cases (38.7%) showed SRIF, which was
      distributed in all lobes of the lungs examined. No differences were observed in
      sex, average age, or smoking history in patients with and without SRIF. There was
      no difference in either the percent or types of adenocarcinoma genetic mutations
      in patients with SRIF versus those without. This data suggests that SRIF does not
      represent an independent risk factor for the development of the major known and
      targeted mutations seen in pulmonary adenocarcinoma. However, additional research
      is required to investigate the potential significance of SRIF in the pathogenesis
      of lung cancer. 

PMID- 24920891
TI  - A randomized controlled trial of inhaled corticosteroids (ICS) on markers of
      epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an
      exploratory proof of concept study.
AB  - BACKGROUND: We recently reported that epithelial-mesenchymal transition (EMT) is
      active in the airways in chronic obstructive pulmonary disease (COPD), suggesting
      presence of an active profibrotic and promalignant stroma. With no data available
      on potential treatment effects, we undertook a blinded analysis of inhaled
      corticosteroids (ICS) effects versus placebo on EMT markers in previously
      obtained endobronchial biopsies in COPD patients, as a "proof of concept" study.
      METHODS: Assessment of the effects of inhaled fluticasone propionate (FP; 500 MUg
      twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone
      propionate and eleven on placebo). The end points were epidermal growth factor
      receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT:
      reticular basement membrane (Rbm) fragmentation ("hallmark" structural marker),
      matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in
      basal epithelial and Rbm cells (mesenchymal transition markers). RESULTS:
      Epithelial activation, "clefts/fragmentation" in the Rbm, and changes in the
      other biomarkers all regressed on ICS, at or close to conventional levels of
      statistical significance. From these data, we have been able to nominate primary
      and secondary end points and develop power calculations that would be applicable
      to a definitive prospective study. CONCLUSION: Although only a pilot "proof of
      concept" study, this trial provided strong suggestive support for an anti-EMT
      effect of ICS in COPD airways. A larger and fully powered prospective study is
      now indicated as this issue is likely to be extremely important. Such studies may
      clarify the links between ICS use and better clinical outcomes and protection
      against lung cancer in COPD.

PMID- 24920892
TI  - Increased serum levels of lipocalin-1 and -2 in patients with stable chronic
      obstructive pulmonary disease.
AB  - Despite a number of studies on biomarkers in chronic obstructive pulmonary
      disease (COPD), only a few disease-related markers have been identified, yet we
      still have no satisfactory markers specific to innate immune system and
      neutrophil activation, which is essential in airway inflammation in COPD. Recent
      biological studies indicated that lipocalins (LCNs) might be involved in airway
      inflammation and innate immunity; however, results from available studies on the
      association of LCNs with COPD are not consistent. We carried out a multicenter
      prospective observational cohort study to investigate the differences in serum
      levels of LCN1 and LCN2 between subjects with COPD (n=58) and healthy controls
      (n=29). Several validated inflammatory markers, including C-reactive protein,
      tumor necrosis factor-alpha, interleukin-6, and interleukin-8, were measured. The
      correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung
      function, symptoms, and disease category was also analyzed. When comparing with
      healthy controls, serum levels of LCN1 (66.35+/-20.26 ng/mL versus 41.16+/-24.19
      ng/mL, P<0.001) and LCN2 (11.29+/-3.92 ng/mL versus 6.09+/-5.13 ng/mL, P<0.001)
      were both elevated in subjects with COPD after adjusting for age, sex, smoking
      habits, and inflammatory biomarkers. Smoking history and tobacco exposure, as
      quantified by pack-year, had no impact on systemic expressions of LCN1 and LCN2
      in our study. Blood levels of LCN1 and LCN2, respectively, were negatively
      correlated to COPD Assessment Test and Modified Medical British Research Council
      score (P<0.001). Disease category by Global Initiative for Chronic Obstructive
      Lung Disease grade 1-4 or group A-D was not associated with levels of LCNs.
      Patient-reported exacerbations and body mass index were also tested, but no
      relationship with LCNs was found. In summary, serum concentrations of LCN1 and
      LCN2 were both elevated in patients with COPD, with their levels correlating to
      COPD Assessment Test and Modified Medical British Research Council score. These
      findings warrant large-scale and longitudinal studies to validate LCNs as
      circulating biomarkers for COPD. 

PMID- 24920893
TI  - Real-world characterization and differentiation of the Global Initiative for
      Chronic Obstructive Lung Disease strategy classification.
AB  - BACKGROUND: This study aimed to characterize and differentiate the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) strategy 2011 cut points
      through the modified Medical Research Council dyspnea scale (mMRC) and chronic
      obstructive pulmonary disease (COPD) assessment test (CAT). METHODS: Analysis of
      COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was
      conducted in Europe and US. Matched data from physicians and patients included
      CAT and mMRC scores. Receiver operating characteristic curves and kappa analysis
      determined a cut point for CAT and mMRC alignment and thus defined patient
      movement ("movers") within GOLD groups A-D, depending on the tool used. Logistic
      regression analysis, with a number of physician- and patient-reported covariates,
      characterized those movers. RESULTS: Comparing GOLD-defined high-symptom patients
      using mMRC and CAT cut points (>=2 and >=10, respectively), there were 890
      (53.65%) movers; 887 of them (99.66%) moved from less symptomatic GOLD groups A
      and C (using mMRC) to more symptomatic groups B and D (using CAT). For receiver
      operating characteristic (area under the curve: 0.82, P<0.001) and kappa
      (maximized: 0.45) recommended CAT cut points of >=24 and >=26, movers reduced to
      429 and 403 patients, respectively. Logistic regression analysis showed variables
      significantly associated with movers were related to impact on normal life, age,
      cough, and sleep (all P<0.05). Within movers, direction of movement was
      significantly associated with the same variables (all P<0.05). CONCLUSION: Use of
      current mMRC or CAT cut points leads to inconsistencies for COPD assessment
      classification. It is recommended that cut points are aligned and both tools
      administered simultaneously for optimal patient care and to allow for closer
      management of movers. Our research may suggest an opportunity to investigate a
      combined score approach to patient management based on the worst result of mMRC
      and CAT. The reduced number of remaining movers may then identify patients who
      have greater impact of disease and may require a more personalized treatment
      plan.

PMID- 24920894
TI  - Prevalence of airflow limitation in outpatients with cardiovascular diseases in
      Japan.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) and chronic obstructive
      pulmonary disease (COPD) commonly coexist and share common risk factors. The
      prevalence of COPD in outpatients with a smoking history and CVD in Japan is
      unknown. The aim of this study was to determine the proportion of Japanese
      patients with a smoking history being treated for CVD who have concurrent airflow
      limitation compatible with COPD. A secondary objective was to test whether the
      usage of lung function tests performed in the clinic influenced the diagnosis
      rate of COPD in the patients identified with airflow limitation. METHODS: In a
      multicenter observational prospective study conducted at 17 centers across Japan,
      the prevalence of airflow limitation compatible with COPD (defined as forced
      expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in
      cardiac outpatients >=40 years old with a smoking history who routinely visited
      the clinic for their CVD. Each patient completed the COPD Assessment Test prior
      to spirometry testing. RESULTS: Data were available for 995 patients with a mean
      age of 66.6+/-10.0 years, of whom 95.5% were male. The prevalence of airflow
      limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients
      (n=236) did not have a prior diagnosis of COPD. The prevalence of previously
      diagnosed airflow limitation was higher in sites with higher usage of lung
      function testing (14.0%, 15.2% respectively) compared against sites where it is
      performed seldom (11.1%), but was still low. CONCLUSION: The prevalence of
      airflow limitation in this study indicates that a quarter of outpatients with CVD
      have COPD, almost all of whom are undiagnosed. This suggests that it is important
      to look routinely for COPD in CVD outpatients.

PMID- 24920895
TI  - Interaction of gelatin with polyenes modulates antifungal activity and
      biocompatibility of electrospun fiber mats.
AB  - Topical application of antifungals does not have predictable or well-controlled
      release characteristics and requires reapplication to achieve therapeutic local
      concentration in a reasonable time period. In this article, the efficacy of five
      different US Food and Drug Administration-approved antifungal-loaded
      (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole)
      electrospun gelatin fiber mats were compared. Morphological studies show that
      incorporation of polyenes resulted in a two-fold increase in fiber diameter and
      the mats inhibit the growth of yeasts and filamentous fungal pathogens.
      Terbinafine-loaded mats were effective against three filamentous fungal species.
      Among the two azole antifungals compared, the itraconazole-loaded mat was potent
      against Aspergillus strains. However, activity loss was observed for fluconazole
      loaded mats against all of the test organisms. The polyene-loaded mats displayed
      rapid candidacidal activities as well. Biophysical and rheological measurements
      indicate strong interactions between polyene antifungals and gelatin matrix. As a
      result, the polyenes stabilized the triple helical conformation of gelatin and
      the presence of gelatin decreased the hemolytic activity of polyenes. The polyene
      loaded fiber mats were noncytotoxic to primary human corneal and sclera
      fibroblasts. The reduction of toxicity with complete retention of activity of the
      polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the
      management of superficial skin infections. 

PMID- 24920896
TI  - Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain
      tumors.
AB  - Pediatric brain tumors (PBTs) are a leading cause of death in children. For an
      improved prognosis in patients with PBTs, there is a critical need to develop
      molecularly-specific imaging agents to monitor disease progression and response
      to treatment. In this paper, we describe manganese-containing Prussian blue
      nanoparticles as agents for molecular magnetic resonance imaging (MRI) and
      fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a
      core lattice structure that incorporates and retains paramagnetic Mn(2+) ions,
      and generates MRI contrast (both negative and positive). The biofunctionalized
      shell is comprised of fluorescent avidin, which serves the dual purpose of
      enabling fluorescence imaging and functioning as a platform for the attachment of
      biotinylated ligands that target PBTs. The surfaces of our nanoparticles are
      modified with biotinylated antibodies targeting neuron-glial antigen 2 or
      biotinylated transferrin. Both neuron-glial antigen 2 and the transferrin
      receptor are protein markers overexpressed in PBTs. We describe the synthesis,
      biofunctionalization, and characterization of these multimodal nanoparticles.
      Further, we demonstrate the MRI and fluorescence imaging capabilities of
      manganese-containing Prussian blue nanoparticles in vitro. Finally, we
      demonstrate the potential of these nanoparticles as PBT imaging agents by
      measuring their organ and brain biodistribution in an orthotopic mouse model of
      PBTs using ex vivo fluorescence imaging. 

PMID- 24920897
TI  - Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous
      nanoparticles.
AB  - pH-sensitive gated mesoporous silica nanoparticles have been synthesized.
      Increased extracellular pH and internalization into living yeast cells triggered
      molecular gate aperture and cargo release. Proper performance of the system was
      demonstrated with nanodevices loaded with fluorescein or with the antifungal
      agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole
      significantly enhanced tebuconazole cytotoxicity. As alterations of acidic
      external pH are a key parameter in the onset of fungal vaginitis, this nanodevice
      could improve the treatment for vaginal mycoses. 

PMID- 24920898
TI  - In situ precipitation: a novel approach for preparation of iron-oxide
      magnetoliposomes.
AB  - BACKGROUND: Conventional methods of preparing magnetoliposomes are complicated
      and inefficient. A novel approach for magnetoliposomes preparation was
      investigated in the study reported here. METHODS: FeCl3/FeCl2 solutions were
      hydrated with lipid films to obtain liposome-encapsulated iron ions by ultrasonic
      dispersion. Non-encapsulated iron ions were removed by dialysis. NH3.H2O was
      added to the system to adjust the pH to a critical value. Four different systems
      were prepared. Each was incubated at a different temperature for a different
      length of time to facilitate the permeation of NH3.H2O into the inner phase of
      the liposomes and the in situ formation of magnetic iron-oxide cores in the
      liposomes. Single-factor analysis and orthogonal-design experiments were applied
      to determinate the effects of alkalization pH, temperature, duration, and initial
      Fe concentration on encapsulation efficiency and drug loading. RESULTS: The
      magnetoliposomes prepared by in situ precipitation had an average particle size
      of 168+/-14 nm, zeta potential of -26.2+/-1.9 mV and polydispersity index of
      0.23+/-0.06. The iron-oxide cores were confirmed as Fe3O4 by X-ray diffraction
      and demonstrated a superparamagnetic response. Encapsulation efficiency ranged
      from 3% to 22%, while drug loading ranged from 0.2 to 1.58 mol Fe/mol lipid. The
      optimal conditions for in situ precipitation were found to be an alkalization pH
      of 12, temperature of 60 degrees C, time of 60 minutes, and initial Fe
      concentration of 100 mM Fe(3+) + 50 mM Fe(2+). CONCLUSION: In situ precipitation
      could be a simple and efficient approach for the preparation of iron-oxide
      magnetoliposomes.

PMID- 24920899
TI  - Amplified voltammetric detection of glycoproteins using 4-mercaptophenylboronic
      acid/biotin-modified multifunctional gold nanoparticles as labels.
AB  - Ultrasensitive detection of protein biomarkers is essential for early diagnosis
      and therapy of many diseases. Glycoproteins, differing from other types of
      proteins, contain carbohydrate moieties in the oligosaccharide chains. Boronic
      acid can form boronate ester covalent bonds with diol-containing species. Herein,
      we present a sensitive and cost-effective electrochemical method for glycoprotein
      detection using 4-mercaptophenylboronic acid (MBA)/biotin-modified gold
      nanoparticles (AuNPs) (MBA-biotin-AuNPs) as labels. To demonstrate the
      feasibility and sensitivity of this method, recombinant human erythropoietin
      (rHuEPO) was tested as a model analyte. Specifically, rHuEPO was captured by the
      anti-rHuEPO aptamer-covered electrode and then derivatized with MBA-biotin-AuNPs
      through the boronic acid-carbohydrate interaction. The MBA-biotin-AuNPs
      facilitated the attachment of streptavidin-conjugated alkaline phosphatase for
      the production of electroactive p-aminophenol from p-aminophenyl phosphate
      substrate. A detection limit of 8 fmol L(-1) for rHuEPO detection was achieved.
      Other glycosylated and non-glycosylated proteins, such as horseradish peroxidase,
      prostate specific antigen, metallothionein, streptavidin, and thrombin showed no
      interference in the detection assay. 

PMID- 24920900
TI  - Liposomes versus metallic nanostructures: differences in the process of knowledge
      translation in cancer.
AB  - This research maps the knowledge translation process for two different types of
      nanotechnologies applied to cancer: liposomes and metallic nanostructures (MNs).
      We performed a structural analysis of citation networks and text mining supported
      in controlled vocabularies. In the case of liposomes, our results identify
      subnetworks (invisible colleges) associated with different therapeutic
      strategies: nanopharmacology, hyperthermia, and gene therapy. Only in the
      pharmacological strategy was an organized knowledge translation process
      identified, which, however, is monopolized by the liposomal doxorubicins. In the
      case of MNs, subnetworks are not differentiated by the type of therapeutic
      strategy, and the content of the documents is still basic research. Research on
      MNs is highly focused on developing a combination of molecular imaging and
      photothermal therapy.

PMID- 24920901
TI  - Rapid efficient synthesis and characterization of silver, gold, and bimetallic
      nanoparticles from the medicinal plant Plumbago zeylanica and their application
      in biofilm control.
AB  - BACKGROUND: Nanoparticles (NPs) have gained significance in medical fields due to
      their high surface-area-to-volume ratio. In this study, we synthesized NPs from a
      medicinally important plant - Plumbago zeylanica. MATERIALS AND METHODS: Aqueous
      root extract of P. zeylanica (PZRE) was analyzed for the presence of flavonoids,
      sugars, and organic acids using high-performance thin-layer chromatography
      (HPTLC), gas chromatography-time of flight-mass spectrometry (GC-TOF-MS), and
      biochemical methods. The silver NPs (AgNPs), gold NPs (AuNPs), and bimetallic NPs
      (AgAuNPs) were synthesized from root extract and characterized using ultraviolet
      visible spectra, X-ray diffraction (XRD), energy-dispersive spectrometry (EDS),
      transmission electron microscopy (TEM), and dynamic light scattering (DLS). The
      effects of these NPs on Acinetobacter baumannii, Staphylococcus aureus, and
      Escherichia coli biofilms were studied using quantitative biofilm inhibition and
      disruption assays, as well as using fluorescence, scanning electron microscopy,
      and atomic force microscopy. RESULTS: PZRE showed the presence of phenolics, such
      as plumbagin, and flavonoids, in addition to citric acid, sucrose, glucose,
      fructose, and starch, using HPTLC, GC-TOF-MS, and quantitative analysis.
      Bioreduction of silver nitrate (AgNO3) and chloroauric acid (HAuCl4) were
      confirmed at absorbances of 440 nm (AgNPs), 570 nm (AuNPs), and 540 nm (AgAuNPs),
      respectively. The maximum rate of synthesis at 50 degrees C was achieved with 5
      mM AgNO3 within 4.5 hours for AgNPs; and with 0.7 mM HAuCl4 within 5 hours for
      AuNPs. The synthesis of AgAuNPs, which completed within 90 minutes with 0.7 mM
      AgNO3 and HAuCl4, was found to be the fastest. Fourier-transform infrared
      spectroscopy confirmed bioreduction, while EDS and XRD patterns confirmed purity
      and the crystalline nature of the NPs, respectively. TEM micrographs and DLS
      showed about 60 nm monodispersed Ag nanospheres, 20-30 nm Au nanospheres adhering
      to form Au nanotriangles, and about 90 nm hexagonal blunt-ended AgAuNPs. These
      NPs also showed antimicrobial and antibiofilm activity against E. coli, A.
      baumannii, S. aureus, and a mixed culture of A. baumannii and S. aureus. AgNPs
      inhibited biofilm in the range of 96%-99% and AgAuNPs from 93% to 98% in single
      culture biofilms. AuNPs also showed biofilm inhibition, with the highest of 98%
      in S. aureus. AgNPs also showed good biofilm disruption, with the highest of 88%
      in A. baumannii. CONCLUSION: This is the first report on rapid and efficient
      synthesis of AgNPs, AuNPs and AgAuNPs from P. zeylanica and their effect on
      quantitative inhibition and disruption of bacterial biofilms.

PMID- 24920902
TI  - Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil
      nanoparticle suspensions of different particle sizes.
AB  - Three tilmicosin-loaded hydrogenated castor oil nanoparticle (TMS-HCO-NP)
      suspensions of different particle sizes were prepared with different polyvinyl
      alcohol surfactant concentrations using a hot homogenization and ultrasonic
      technique. The in vitro release, in vitro antibacterial activity, mammalian
      cytotoxicity, acute toxicity in mice, and stability study were conducted to
      evaluate the characteristics of the suspensions. The in vitro tilmicosin release
      rate, antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and
      stability of the suspensions were evaluated. When prepared with polyvinyl alcohol
      concentrations of 0.2%, 1%, and 5%, the mean diameters of the nanoparticles in
      the three suspensions were 920+/-35 nm, 452+/-10 nm, and 151+/-4 nm,
      respectively. The three suspensions displayed biphasic release profiles similar
      to that of freeze-dried TMS-HCO-NP powders, with the exception of having a faster
      initial release. Moreover, suspensions of smaller-sized particles showed faster
      initial release, and lower minimum inhibitory concentrations and minimum
      bactericidal concentrations. Time-kill curves showed that within 12 hours, the
      suspension with the 151 nm particles had the most potent bactericidal activity,
      but later, the suspensions with larger-sized particles showed increased
      antibacterial activity. None of the three suspensions were cytotoxic at clinical
      dosage levels. At higher drug concentrations, all three suspensions showed
      similar concentration-dependent cytotoxicity. The suspension with the smallest
      sized particle showed significantly more acute toxicity in mice, perhaps due to
      faster drug release. All three suspensions exhibited good stability at 4 degrees
      C and at room temperature for at least 6 months. These results demonstrate that
      TMS-HCO-NP suspensions can be a promising formulation for tilmicosin, and that
      nanoparticle size can be an important consideration for formulation development. 

PMID- 24920903
TI  - Mesoporous magnesium silicate-incorporated poly(epsilon-caprolactone)
      poly(ethylene glycol)-poly(epsilon-caprolactone) bioactive composite beneficial
      to osteoblast behaviors.
AB  - Mesoporous magnesium silicate (m-MS) and poly(epsilon-caprolactone)-poly(ethylene
      glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) composite (m-MPC) was
      synthesized by solvent casting method. The results suggest that the mechanical
      properties of compressive strength and elastic modulus, as well as
      hydrophilicity, of the m-MPC increased with increase of m-MS content in the
      composites. In addition, the weight loss of the m-MPC improved significantly with
      the increase of m-MS content during composite soaking in phosphate-buffered
      saline for 10 weeks, indicating that incorporation of m-MS into PCL-PEG-PCL could
      enhance the degradability of the m-MPC. Moreover, the m-MPC with 40 w% m-MS could
      induce a dense and continuous apatite layer on its surface after soaking in
      simulated body fluid for 5 days, which was better than m-MPC 20 w% m-MS,
      exhibiting excellent in vitro bioactivity. In cell cultural experiments, the
      results showed that the attachment and viability ratio of MG63 cells on m-MPC
      increased significantly with the increase of m-MS content, showing that the
      addition of m-MS into PCL-PEG-PCL could promote cell attachment and
      proliferation. The results suggest that the incorporation of m-MS into PCL-PEG
      PCL could produce bioactive composites with improved hydrophilicity,
      degradability, bioactivity, and cytocompatibility. 

PMID- 24920904
TI  - Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF
      loaded nanospheres in a partial lesion model of Parkinson's disease.
AB  - Current research efforts are focused on the application of growth factors, such
      as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial
      growth factor (VEGF), as neuroregenerative approaches that will prevent the
      neurodegenerative process in Parkinson's disease. Continuing a previous work
      published by our research group, and with the aim to overcome different
      limitations related to growth factor administration, VEGF and GDNF were
      encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy
      facilitates the combined administration of the VEGF and GDNF into the brain of 6
      hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and
      simultaneous drug release. The NS particle size was about 200 nm and the
      simultaneous addition of VEGF NS and GDNF NS resulted in significant protection
      of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic
      acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the
      amphetamine rotation behavior test was carried out over 10 weeks, in order to
      check for in vivo efficacy. The results showed that VEGF NS and GDNF NS
      significantly decreased the number of amphetamine-induced rotations at the end of
      the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the
      striatum and the external substantia nigra confirmed a significant enhancement of
      neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of
      VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a
      valuable neurogenerative/neuroreparative approach for treating Parkinson's
      disease. 

PMID- 24920905
TI  - Calcifying nanoparticles promote mineralization in vascular smooth muscle cells:
      implications for atherosclerosis.
AB  - BACKGROUND: Nano-sized complexes of calcium phosphate mineral and proteins
      (calcifying nanoparticles [CNPs]) serve as mineral chaperones. Thus, CNPs may be
      both a result and cause of soft tissue calcification processes. This study
      determined if CNPs could augment calcification of arterial vascular smooth muscle
      cells in vitro. METHODS: CNPs 210 nm in diameter were propagated in vitro from
      human serum. Porcine aortic smooth muscle cells were cultured for up to 28 days
      in medium in the absence (control) or presence of 2 mM phosphate ([P] positive
      calcification control) or after a single 3-day exposure to CNPs. Transmission
      electron-microscopy was used to characterize CNPs and to examine their cellular
      uptake. Calcium deposits were visualized by light microscopy and von Kossa
      staining and were quantified by colorimetry. Cell viability was quantified by
      confocal microscopy of live-/dead-stained cells and apoptosis was examined
      concurrently by fluorescent labeling of exposed phosphatidylserine. RESULTS:
      CNPs, as well as smaller calcium crystals, were observed by transmission electron
      microscopy on day 3 in CNP-treated but not P-treated cells. By day 28, calcium
      deposits were visible in similar amounts within multicellular nodules of both CNP
      and P-treated cells. Apoptosis increased with cell density under all treatments.
      CNP treatment augmented the density of apoptotic bodies and cellular debris in
      association with mineralized multicellular nodules. CONCLUSION: Exogenous CNPs
      are taken up by aortic smooth muscle cells in vitro and potentiate accumulation
      of smooth-muscle-derived apoptotic bodies at sites of mineralization. Thus, CNPs
      may accelerate vascular calcification.

PMID- 24920906
TI  - Effect of additive particles on mechanical, thermal, and cell functioning
      properties of poly(methyl methacrylate) cement.
AB  - The most common bone cement material used clinically today for orthopedic surgery
      is poly(methyl methacrylate) (PMMA). Conventional PMMA bone cement has several
      mechanical, thermal, and biological disadvantages. To overcome these problems,
      researchers have investigated combinations of PMMA bone cement and several
      bioactive particles (micrometers to nanometers in size), such as magnesium oxide,
      hydroxyapatite, chitosan, barium sulfate, and silica. A study comparing the
      effect of these individual additives on the mechanical, thermal, and cell
      functional properties of PMMA would be important to enable selection of suitable
      additives and design improved PMMA cement for orthopedic applications. Therefore,
      the goal of this study was to determine the effect of inclusion of magnesium
      oxide, hydroxyapatite, chitosan, barium sulfate, and silica additives in PMMA on
      the mechanical, thermal, and cell functional performance of PMMA. American
      Society for Testing and Materials standard three-point bend flexural and fracture
      tests were conducted to determine the flexural strength, flexural modulus, and
      fracture toughness of the different PMMA samples. A custom-made temperature
      measurement system was used to determine maximum curing temperature and the time
      needed for each PMMA sample to reach its maximum curing temperature. Osteoblast
      adhesion and proliferation experiments were performed to determine cell viability
      using the different PMMA cements. We found that flexural strength and fracture
      toughness were significantly greater for PMMA specimens that incorporated silica
      than for the other specimens. All additives prolonged the time taken to reach
      maximum curing temperature and significantly improved cell adhesion of the PMMA
      samples. The results of this study could be useful for improving the union of
      implant-PMMA or bone-PMMA interfaces by incorporating nanoparticles into PMMA
      cement for orthopedic and orthodontic applications. 

PMID- 24920908
TI  - Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based
      nanosuspensions in H22-bearing mice.
AB  - PURPOSE: N3-O-toluyl-fluorouracil (TFU) is a potential antitumor prodrug of 5
      fluorouracil (5-FU), but its poor solubility has limited its use in clinic. This
      study aimed to improve the bioavailability of TFU by preparing TFU-loaded lipid
      based nanosuspensions (TFU-LNS) and perform a preclinical evaluation. METHODS:
      TFU-LNS were prepared through high-pressure homogenization and were lyophilized
      afterwards. For in vitro test, the physicochemical properties and cytotoxicity
      against HegG2 cells were conducted. For in vivo evaluation, the pharmacokinetics,
      tissue distribution, and antitumor efficacy were investigated in H22-bearing
      Kunming mice. RESULTS: TFU showed different degradability in four media; in
      particular, nearly all of it converted to an equimolar amount of 5-FU in blank
      plasma of Wistar rats. The lyophilized TFU-LNS had a mean particle size of
      180.03+/-3.11 nm and zeta potential of -8.02+/-1.43 mV and showed no discernible
      changes after storage at 4 degrees C for 3 months. In the in vivo antitumor
      study, the antitumor efficacy of TFU-LNS was consistent with that of 5-FU
      injection. Furthermore, TFU-LNS released a lower concentration of 5-FU in heart
      and kidney throughout the tissue distribution studies. CONCLUSION: TFU-LNS
      exhibited convincing antitumor activity and easy scale-up opportunity, which
      suggests that TFU-LNS might be a promising drug delivery system for cancer
      therapy.

PMID- 24920907
TI  - Multifunctional materials for bone cancer treatment.
AB  - The purpose of this review is to present the most recent findings in bone tissue
      engineering. Special attention is given to multifunctional materials based on
      collagen and collagen-hydroxyapatite composites used for skin and bone cancer
      treatments. The multi-functionality of these materials was obtained by adding to
      the base regenerative grafts proper components, such as ferrites (magnetite being
      the most important representative), cytostatics (cisplatin, carboplatin,
      vincristine, methotrexate, paclitaxel, doxorubicin), silver nanoparticles,
      antibiotics (anthracyclines, geldanamycin), and/or analgesics (ibuprofen,
      fentanyl). The suitability of complex systems for the intended applications was
      systematically analyzed. The developmental possibilities of multifunctional
      materials with regenerative and curative roles (antitumoral as well as pain
      management) in the field of skin and bone cancer treatment are discussed. It is
      worth mentioning that better materials are likely to be developed by combining
      conventional and unconventional experimental strategies. 

PMID- 24920909
TI  - Mussel-inspired human gelatin nanocoating for creating biologically adhesive
      surfaces.
AB  - Recombinant human gelatin was conjugated with dopamine using carbodiimide as a
      surface modifier. This dopamine-coupled human gelatin (D-rhG) was characterized
      by (1)H-nuclear magnetic resonance, mass spectroscopy, and circular dichroism. D
      rhG-coated surface properties were analyzed by physicochemical methods.
      Additionally, cell attachment and growth on the modified surfaces was assessed
      using human umbilical endothelial cells. Binding of gelatin onto titanium was
      significantly enhanced by dopamine conjugation. The thickness of the D-rhG
      coating depended on the treatment pH; thicker layers were formed at higher pH
      values, with a maximum thickness of 30 nm. D-rhG enhanced the binding of collagen
      binding vascular endothelial growth factor and cell adhesion as compared with
      gelatin alone, even at the same surface concentration. The D-rhG surface modifier
      enhanced substrate binding by creating an adhesive nanointerface that increased
      specific protein binding and cell attachment. 

PMID- 24920910
TI  - Epileptic and cognitive changes in children with cerebral palsy: an Egyptian
      study.
AB  - BACKGROUND: Cerebral palsy (CP) is the most frequent cause of motor handicap
      among children. AIM OF THE STUDY: We aim to study the relation of epilepsy in
      children with CP to various risk factors that affect the development of seizures.
      PATIENTS AND METHODS: In a cross-sectional, descriptive, population-based, case
      control study, 98 children with CP (48 children with CP with epilepsy, and 50
      children with CP without epilepsy) were compared with 180 children without CP or
      seizures. The children lived in two regions in Egypt: the Al-Kharga District-New
      Valley and El-Quseir city-Red Sea. These cases were subjected to meticulous
      neurological assessment, brain magnetic resonance imaging,
      electroencephalography, and Stanford-Binet (4th edition) examination. Multinomial
      logistic regression was used to assess the risk factors. RESULTS: Epilepsy was
      diagnosed in 48.9% of all cases of CP. Mental subnormality was observed more
      frequently in children with epilepsy than in those without epilepsy (84.6% versus
      66.7%). The frequency of epilepsy was highest in patients with the spastic
      quadriplegic type of illness (58.3%). Multinomial logistic regression revealed
      that prematurity (<32 weeks of pregnancy), low birth weight (<2.5 kg at birth),
      neonatal seizures, jaundice, and cyanosis were significantly associated with CP
      with epilepsy. CONCLUSION: CP is associated with a high percentage of seizure
      disorders. Prematurity, low birth weight, neonatal seizures, cyanosis, and
      jaundice are significant risk factors among patients with CP with epilepsy
      compared to patients with CP without epilepsy or a healthy control group.

PMID- 24920911
TI  - Evolving treatment approaches for the management of metastatic castration
      resistant prostate cancer - role of radium-223.
AB  - Radium-223 is a first-in-class alpha particle-emitting radiopharmaceutical
      approved for the treatment of bone metastatic castration-resistant prostate
      cancer. Radium-223 is administered intravenously with no requirement for complex
      shielding and specifically targets areas of bone metastasis. In a randomized
      placebo-controlled Phase III study, treatment with radium-223 was shown to
      improve overall survival, time to skeletal-related events, and health-related
      quality of life. Apart from radium-223, the cytotoxic chemotherapy agents
      docetaxel and cabazitaxel, androgen biosynthesis inhibitor abiraterone acetate,
      novel anti-androgen enzalutamide, and immunotherapy sipuleucel-T have also been
      shown to improve survival of men with advanced prostate cancer in Phase III
      trials. This review will outline current treatment approaches for advanced
      prostate cancer with a focus on the role of radium-223 in changing treatment
      paradigms. 

PMID- 24920912
TI  - The impact of intrahepatic cholestasis of pregnancy with hepatitis B virus
      infection on perinatal outcomes.
AB  - INTRODUCTION: To investigate the impact of intrahepatic cholestasis of pregnancy
      (ICP) with hepatitis B virus (HBV) infection on perinatal outcomes. METHODS: In
      the study, 200 pregnant women were divided into four groups, including 50 cases
      with ICP and HBV infection, 50 cases with ICP, 50 cases with HBV infection, and
      50 healthy pregnancies. The delivery process and perinatal outcomes were analyzed
      among different groups. RESULTS: When compared to the healthy pregnancy group,
      significantly increased rates of premature rupture of membranes, meconium-stained
      amniotic fluid, and cesarean section were observed in cases of ICP, HBV
      infection, or ICP patients with HBV (P<0.05). Specifically, the rates of HBV
      infection in the newborn, fetal distress, neonatal asphyxia, and birth defects in
      the newborn, and infant Apgar scores were higher in ICP pregnancies with HBV
      (56%, 48%, 16%, and 48%, respectively) than in the other groups (P<0.05).
      CONCLUSION: ICP combined with HBV infection has a clear influence on perinatal
      infant outcomes.

PMID- 24920913
TI  - New treatments for genotype 1 chronic hepatitis C - focus on simeprevir.
AB  - Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and
      hepato cellular carcinoma. In the USA, Canada, and Japan, simeprevir - one of the
      second-generation HCV NS3/4A protease inhibitors - in combination with
      peginterferon alpha-2a or 2b plus ribavirin has recently been approved for HCV
      genotype 1-infected patients and is now used in daily clinical practice. This
      review summarizes the mechanism of action of simeprevir and the results of
      clinical trials of simeprevir and peginterferon plus ribavirin for HCV genotype 1
      patients. In general, the simeprevir and peginterferon plus ribavirin treatment
      is highly effective and its adverse events are similar to those of peginterferon
      plus ribavirin only, the exception being milder, reversible jaundice. In the near
      future, the development of interferon-free regimens with simeprevir is expected.
      Careful attention should be paid to new results of clinical trials with
      simeprevir. 

PMID- 24920914
TI  - Cabozantinib for progressive metastatic medullary thyroid cancer: a review.
AB  - Medullary thyroid cancer is uncommon and patients typically present with advanced
      disease. Treatment options for patients with progressive, metastatic medullary
      thyroid cancer had been limited until recently. Tyrosine kinase inhibitors have
      garnered increasing interest in this subset of patients. The US Food and Drug
      Administration recently approved cabozantinib, a tyrosine kinase inhibitor, after
      promising results were shown in a large Phase III clinical trial. This review
      summarizes the clinical pharmacology, clinical trials, and safety data for
      cabozantinib and concludes with a discussion of possible future directions for
      the treatment of medullary thyroid cancer. 

PMID- 24920915
TI  - A double-blind, randomized trial, including frequent patient-physician contacts
      and Ramadan-focused advice, assessing vildagliptin and gliclazide in patients
      with type 2 diabetes fasting during Ramadan: the STEADFAST study.
AB  - BACKGROUND: Several observational studies were conducted with vildagliptin in
      patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan, showing
      significantly lower incidences of hypoglycemia with vildagliptin versus
      sulfonylureas, including gliclazide. It was of interest to complement the
      existing real-life evidence with data from a randomized, double-blind, clinical
      trial. CLINICAL TRIALS IDENTIFIER: NCT01758380. METHODS: This multiregional,
      double-blind study randomized 557 patients with T2DM (mean glycated hemoglobin
      [HbA1c], 6.9%), previously treated with metformin and any sulfonylurea to receive
      either vildagliptin (50 mg twice daily) or gliclazide plus metformin. The study
      included four office visits (three pre-Ramadan) and multiple telephone contacts,
      as well as Ramadan-focused advice. Hypoglycemic events were assessed during
      Ramadan; HbA(1c) and weight were analyzed before and after Ramadan. RESULTS: The
      proportion of patients reporting confirmed (<3.9 mmol/L and/or severe)
      hypoglycemic events during Ramadan was 3.0% with vildagliptin and 7.0% with
      gliclazide (P=0.039; one-sided test), and this was 6.0% and 8.7%, respectively,
      for any hypoglycemic events (P=0.173). The adjusted mean change pre- to post
      Ramadan in HbA(1c) was 0.05%+/-0.04% with vildagliptin and -0.03%+/-0.04% with
      gliclazide, from baselines of 6.84% and 6.79%, respectively (P=0.165). In both
      groups, the adjusted mean decrease in weight was -1.1+/-0.2 kg (P=0.987). Overall
      safety was similar between the treatments. CONCLUSION: In line with the results
      from previous observational studies, vildagliptin was shown in this
      interventional study to be an effective, safe, and well-tolerated treatment in
      patients with T2DM fasting during Ramadan, with a consistently low incidence of
      hypoglycemia across studies, accompanied by good glycemic and weight control. In
      contrast, gliclazide showed a lower incidence of hypoglycemia in the present
      interventional than the previous observational studies. This is suggested to be
      linked to the specific circumstances of this study, including frequent patient
      physician contacts, Ramadan-focused advice, a recent switch in treatment, and
      very well-controlled patients, which is different from what is often seen in real
      life.

PMID- 24920916
TI  - Sensory impairments in community health care: a descriptive study of hearing and
      vision among elderly Norwegians living at home.
AB  - BACKGROUND: Hearing and vision impairments increase with age and are common risk
      factors for functional decline reduced social participation and withdrawal.
      OBJECTIVE: Describe the hearing and vision of home care patients older than 80
      years. METHODS: Ninety-three older adults (80+ years) receiving home care were
      screened for hearing and vision in their homes. Data were collected using a HEINE
      Mini 3000((r)) Otoscope to examine the eardrum and presence of earwax, an Entomed
      SA201-IV portable pure-tone audiometer to measure the pure-tone average (PTAV), a
      logarithm of the minimum angle of resolution chart to measure visual acuity (VA),
      and the Combined Serious Sensory Impairment interview guide. RESULTS: Slight and
      moderate hearing impairments were found in 41% and 47% of the population,
      respectively (mean PTAV =40.4 dB for the better ear), and 40% and 56% had
      impaired and slightly impaired vision, respectively (mean VA =0.45 for the better
      eye). The participants' self-assessments of hearing and vision were only weakly
      correlated with PTAV and VA values. The visual function was significantly worse
      in men than in women (P=0.033). Difficulty in performing instrumental activities
      of daily living because of hearing and vision impairments was experienced by 17%
      of the participants, whereas 76% experienced no difficulties. When many people
      were present, 72% of the participants found it difficult to understand speech.
      Nearly 30% found it tiring to read, and 41% could not read very small print.
      CONCLUSION: The patients' self-assessments of their hearing and vision did not
      correlate strongly with their VA and PTAV scores. Asking the elderly about their
      overall hearing and vision ability is not sufficient for detecting sensory
      impairment, and asking more specific questions about what they could not hear and
      see was not an adequate indicator of the patients' hearing and vision problems.
      To detect hearing and vision impairments among elderly home care patients,
      standardized measurements of their hearing and vision are necessary.

PMID- 24920917
TI  - Overcoming obstacles to establish a multidisciplinary team approach to
      hepatobiliary diseases: a working model in a Caribbean setting.
AB  - INTRODUCTION: By providing a structured forum to exchange information and ideas,
      multidisciplinary team meetings improve working relationships, expedite
      investigations, promote evidence-based treatment, and ultimately improve clinical
      outcomes. METHODS: This discursive paper reports the introduction of a
      multidisciplinary team approach to manage hepatobiliary diseases in Jamaica,
      focusing on the challenges encountered and the methods used to overcome these
      obstacles. CONCLUSION: Despite multiple challenges in resource-limited
      environments, a multidisciplinary team approach can be incorporated into clinical
      practice in developing nations. Policy makers should make it a priority to
      support clinical, operational, and governance aspects of the multidisciplinary
      teams.

PMID- 24920918
TI  - Australian physiotherapists and their engagement with people with chronic pain:
      do their emotional responses affect practice?
AB  - This study explores the experiences of Australian physiotherapists who see people
      with chronic pain as part of their daily practice. It has been established in the
      literature that Australian physiotherapists do not manage people with chronic
      pain well; however, the reasons for this are not well understood. This study
      aimed to explore this phenomenon through a qualitative approach that generated
      data about the perceptions of physiotherapists in regard to caring for people
      with chronic pain. Fourteen physiotherapists were interviewed using a semi
      structured interview approach. The results indicate that the therapists
      experience emotional responses to people with chronic pain, which lead to
      difficulties in being able to successfully provide effective care. These findings
      also provide the beginnings of a framework that may support physiotherapists in
      engaging more successfully with people with chronic pain. 

PMID- 24920919
TI  - Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase
      and mTOR inhibition in anaplastic large cell lymphoma.
AB  - BACKGROUND: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of
      rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in
      anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic
      lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual
      PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma
      cell lines in vitro and in vivo and performed an early response evaluation with
      positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2
      [(18)F]fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[(18)F]
      fluorothymidine (FLT). METHODS: The biological effects of BGT226 were determined
      in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5
      Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide
      staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET
      and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or
      Karpas299 xenografts at baseline and 7 days after initiation of treatment with
      BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation
      and apoptosis to correlate PET findings with in vivo treatment effects. RESULTS:
      SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in
      G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299
      cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET
      discriminated sensitive from resistant lymphoma, as indicated by a significant
      reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma
      bearing animals compared with the control group, but not in animals with
      Karpas299 xenografts. Imaging results correlated with a marked decrease in the
      proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved
      caspase 3, as revealed by immunostaining of explanted lymphoma tissue.
      CONCLUSION: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive
      anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET
      early on in the course of therapy.

PMID- 24920920
TI  - Prior EGFR tyrosine-kinase inhibitor therapy did not influence the efficacy of
      subsequent pemetrexed plus platinum in advanced chemonaive patients with EGFR
      mutant lung adenocarcinoma.
AB  - BACKGROUND: Tumor cells before and after epidermal growth-factor receptor (EGFR)
      tyrosine-kinase inhibitor (TKI) therapy might display different characteristics.
      The aim of this study was to evaluate the influence of prior EGFR TKI therapy on
      the efficacy of subsequent pemetrexed plus platinum (PP) in advanced chemonaive
      patients with EGFR-mutant lung adenocarcinoma. MATERIALS AND METHODS: Advanced
      chemonaive patients with EGFR-mutant lung adenocarcinoma receiving PP as first
      line chemotherapy were enrolled retrospectively in two medical centers of Taiwan.
      The objective of this study was to compare objective response rate (ORR), disease
      control rates (DCR), progression-free survival (PFS), and overall survival (OS)
      of PP in patients with and without prior EGFR TKI therapy. RESULTS: In total, 105
      patients were analyzed. Sixty-one patients (58.1%) had prior EGFR TKI therapy and
      used PP as second-line treatment. The other 44 patients (41.9%) received PP as
      first-line therapy. ORRs of PP in patients with and without prior EGFR TKI
      therapy were 24.6% and 38.6%, respectively (P=0.138). DCRs of the two groups were
      62.3% and 65.9%, respectively (P=0.837). The median PFS (6.1 versus 6.1 months,
      P=0.639) and OS (34.4 versus 32.3 months, P=0.394) were comparable between the
      groups with and without prior EGFR TKI therapy. In a subgroup analysis of
      patients with prior EGFR TKI therapy, there was no significant association
      between the efficacy of first-line EGFR TKI and the outcome of subsequent PP
      therapy. CONCLUSION: Our results suggested that prior EGFR TKI therapy would not
      influence the efficacy of subsequent PP therapy in advanced chemonaive patients
      with EGFR-mutant lung adenocarcinoma.

PMID- 24920921
TI  - Preliminary analysis of the risk factors for radiation pneumonitis in patients
      with non-small-cell lung cancer treated with concurrent erlotinib and thoracic
      radiotherapy.
AB  - PURPOSE: The aim of this study was to investigate radiation pneumonitis and its
      associated risk factors in patients with non-small-cell lung cancer treated with
      concurrent erlotinib and thoracic radiotherapy. MATERIALS AND METHODS: We
      conducted an analysis of patients with nonoperable stage IIIA-IV non-small-cell
      lung cancer who were treated with concurrent thoracic radiotherapy and erlotinib
      (ClinicalTrials.gov identifier: NCT00973310). The Common Terminology Criteria for
      Adverse Events version 3.0 grading system was applied to evaluate the incidence
      of radiation pneumonitis. The lung dosimetric parameters were recorded in
      accordance with the treatment plan, and the study endpoint was radiation
      pneumonitis at grade 2 or more. RESULTS: Among the 24 selected clinical cases,
      nine were identified with radiation pneumonitis of grade 2 or above (37.5%). This
      included four cases with grade 2 (16.7%), two cases with grade 3 (8.3%), and
      three cases with grade 5 (12.5%). The results showed that the planning target
      volume was a significant factor affecting the incidence of radiation pneumonitis.
      All lung dosimetric parameters exhibited statistically significant differences
      between patients with pneumonitis and patients without pneumonitis. The receiver
      operating characteristic (ROC) curve analysis showed that all lung dosimetric
      parameters were useful in predicting the incidence of radiation pneumonitis. In
      addition, the threshold values of V5, V10, V15, V20, V30, and mean lung dose were
      >44%, >29%, >27%, >22%, >17% and >1,027 cGy, respectively. CONCLUSION: Special
      attention should be paid to the adverse effects of radiation pneumonitis in
      concurrent thoracic radiotherapy and erlotinib treatment. Lung dosimetric
      parameters are important predictive factors in radiation pneumonitis.

PMID- 24920923
TI  - Comprehensive clinical and pathological analysis of aggressive renal epithelioid
      angiomyolipoma: report of three cases.
AB  - Renal angiomyolipoma (AML) is recognized as a benign hamartomatous lesion arising
      in the kidney with no obvious malignant potential. However, epithelioid AML
      (EAML), a rare variant of AML, is potentially malignant, with aggressive clinical
      features. It can occur in patients with or without tuberous sclerosis. Because
      EAML may mimic renal cell carcinoma in imaging studies, differentiation of this
      tumor from renal cell carcinoma preoperatively is difficult. At times, the
      lesions may extend into the renal vein and inferior vena cava or metastasize to
      other organs such as the lung and liver. To clarify the biological nature of
      EAML, three specific cases that we encountered in clinical practice are analyzed
      and reported in detail. 

PMID- 24920922
TI  - Prevalence and relationship between major depressive disorder and lung cancer: a
      cross-sectional study.
AB  - OBJECTIVE: The aims of this study were to estimate the prevalence and examine the
      factors associated with major depressive disorder (MDD) in lung cancer patients.
      MATERIALS AND METHODS: This cross-sectional study was carried out in the oncology
      clinic of the University Hospital, Chiang Mai University, Thailand. Patients with
      all stages of lung cancer were included in this study. Demographic data of
      eligible patients were gathered. The Mini-International Neuropsychiatric
      Interview, Thai version 5.0.0 was used to identify MDD. The Thai version of the
      Personal Health Questionnaire Depression Scale was used to assess depression
      severity. RESULTS: A total of 146 lung cancer patients from the outpatient clinic
      from July to December 2012 were approached. The 104 patients were included and
      analyzed in this study. Based on the Mini-International Neuropsychiatric
      Interview, 14.4% of them were defined as having MDD. Multiple linear regression
      analysis revealed that Chalder Fatigue Scale, Functional Assessment of Cancer
      Therapy - Lung, and Pittsburgh Sleep Quality Index scores were significantly
      correlated with MDD in lung cancer patients. CONCLUSION: The results suggest that
      MDD is more prevalent in lung cancer patients. In addition, fatigue, poor quality
      of life, and sleep disturbance may increase associated MDD. Because of the small
      sample size, further studies should be conducted to confirm these results.

PMID- 24920924
TI  - Serial changes of clinical parameters in a patient with advanced hepatocellular
      carcinoma with portal vein thrombosis achieving complete response after treatment
      with sorafenib.
AB  - The prognosis is usually poor in advanced hepatocellular carcinoma (HCC).
      Sorafenib is approved for Child-Pugh class A patients with unresectable and
      advanced HCC. We report here a rare case of a patient with advanced HCC with
      right portal vein thrombosis (PVT) who achieved a complete response after
      treatment with sorafenib. This 74-year-old man was a case of non-hepatitis B and
      C virus-related cirrhosis. Multiphase liver computed tomography showed an 8 cm
      tumor with early enhance, early wash out, and right PVT at segment 8 of the right
      lobe. A liver tumor biopsy confirmed the diagnosis of poorly differentiated HCC.
      Blood tests showed Child-Pugh class A cirrhosis and an alpha-fetoprotein level of
      33,058 ng/mL. Sorafenib was initiated at 800 mg/day but was eventually reduced to
      400 mg every other day because of a grade 3 hand-foot skin reaction. The alpha
      fetoprotein (AFP) level decreased rapidly with a linear trend after treatment.
      After log transformation, the calculated half-life of AFP was 6.84 days. There
      was no more tumor arterial enhancement, and tumor size was decreased to 3.7 cm on
      day 42. PVT shrank gradually and localized to the right anterior branch at month
      9. There was no recurrence of tumor at the end of follow-up in month 19. Typical
      serial changes of clinical parameters were demonstrated in this patient. 

PMID- 24920925
TI  - Cerium oxide nanoparticles in cancer.
AB  - With the development of many nanomedicines designed for tumor therapy, the
      diverse abilities of cerium oxide nanoparticles (CONPs) have encouraged
      researchers to pursue CONPs as a therapeutic agent to treat cancer. Research data
      have shown CONPs to be toxic to cancer cells, to inhibit invasion, and to
      sensitize cancer cells to radiation therapy and chemotherapy. CONPs also display
      minimal toxicity to normal tissues and provide protection from various forms of
      reactive oxygen species generation. Differential cytotoxicity is important for
      anticancer drugs to distinguish effectively between tumor cells and normal cells.
      The antioxidant capabilities of CONPs, which enable cancer therapy protection,
      have also resulted in the exploration of these particles as a potential
      anticancer treatment. Taken together, CONPs might be a potential nanomedicine for
      cancer therapy and this review highlights the current research into CONPs as a
      novel therapeutic for the treatment of cancer. 

PMID- 24920926
TI  - Critical appraisal of the role of gefitinib in the management of locally advanced
      or metastatic non-small cell lung cancer.
AB  - Past studies have demonstrated that epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors can significantly improve clinical outcomes in
      patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
      and sensitive EGFR gene mutations. Gefitinib (Iressa((r))), the first oral EGFR
      tyrosine kinase inhibitor, has been shown to be more effective and better
      tolerated than chemotherapy either in first-line or second-line treatment for
      patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely,
      among patients with wild-type EGFR, gefitinib is inferior to standard
      chemotherapy in both the first-line and second-line settings. Further, gefitinib
      is effective in patients with brain metastases because of its low molecular
      weight and excellent penetration of the blood-brain barrier. In this review, we
      summarize the current data from clinical trials with gefitinib and appraise its
      role in the management of locally advanced or metastatic NSCLC. 

PMID- 24920927
TI  - Clinical significance of promoter region hypermethylation of microRNA-148a in
      gastrointestinal cancers.
AB  - BACKGROUND: MicroRNAs are associated with tumor genesis and progression in
      various carcinomas. MicroRNA-148a (miR-148a) was reported to have low expression
      in gastrointestinal cancers, and might be regulated by promoter region DNA
      methylation. METHODS: Bisulfite-modified sequencing was used to determine the
      promoter region DNA methylation status of human gastrointestinal cancer cell
      lines. Expression levels of miR-148a in cell lines treated with 5-aza-2'
      deoxycytidine were determined by quantitative real-time polymerase chain
      reaction. Total DNA was extracted from the tissues of 64 patients with gastric
      cancer and 51 patients with colorectal cancer. Methylation status was determined
      by methylation-specific polymerase chain reaction. All statistical analyses were
      performed with SPSS 17.0 software. RESULTS: The promoter regions of genes in
      human gastrointestinal cancer cell lines were all hypermethylated, except for HT
      29, and the expression of miR-148a tended to be higher than in controls after
      treatment with 5-aza-2'-deoxycytidine. The methylation-specific polymerase chain
      reaction results showed that 56.25% of gastric cancer tissues and 19.61% of
      colorectal cancer tissues were hypermethylated. A strong correlation was found
      between the expression of miR-148a and the methylation status of promoter regions
      (P<0.001, chi-square test and Pearson's correlation). Furthermore, promoter
      region CpG site hypermethylation of miR-148a was correlated with increased tumor
      size (P=0.01) in gastric cancer after analyzing the correlation between
      methylation status and clinicopathologic characteristics. CONCLUSION: The
      promoter region CpG sites were hypermethylated in gastrointestinal cancers.
      Promoter region hypermethylation status was associated with the expression of miR
      148a and tumor invasiveness in gastric cancer, and may prove to be a new
      biomarker and method for treating gastric cancer.

PMID- 24920928
TI  - Elimination diets in the management of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis, an increasingly recognized chronic inflammatory
      disorder isolated to the esophagus, is triggered by an abnormal allergic response
      to dietary antigens. Current treatment includes swallowed topical steroids and
      dietary modification, which aim to resolve symptoms and prevent long-term
      complications such as formation of strictures. The dietary approach has become
      more widely accepted because long-term steroid therapy is associated with
      potential risks. Dietary treatment includes elemental and elimination diets. An
      exclusive elemental diet, which requires replacement of all intact protein with
      amino acid-based formula, offers the best response of all available therapies,
      with remission in up to 96% of subjects proving it to be superior to all other
      available therapies including topical steroids. However, compliance with this
      approach is challenging because of poor taste and monotony. The high cost of
      formula and the associated psychosocial problems are additional drawbacks of this
      approach. Empiric and allergy test-directed elimination diets have gained
      popularity given that elimination of a limited number of foods is much easier and
      as such is more readily acceptable. There is a growing body of literature
      supporting this type of therapy in both children and adults. This paper reviews
      the evidence for all types of dietary therapy in eosinophilic esophagitis. 

PMID- 24920929
TI  - Holistic approach to prevention and management of type 2 diabetes mellitus in a
      family setting.
AB  - Diabetes mellitus (DM) is a chronic, progressive metabolic disorder with several
      complications that affect virtually all the systems in the human body. Type 2 DM
      (T2DM) is a major risk factor for cardiovascular disease (CVD). The management of
      T2DM is multifactorial, taking into account other major modifiable risk factors,
      like obesity, physical inactivity, smoking, blood pressure, and dyslipidemia. A
      multidisciplinary team is essential to maximize the care of individuals with DM.
      DM self-management education and patient-centered care are the cornerstones of
      management in addition to effective lifestyle strategies and pharmacotherapy with
      individualization of glycemic goals. Robust evidence supports the effectiveness
      of this approach when implemented. Individuals with DM and their family members
      usually share a common lifestyle that, not only predisposes the non-DM members to
      developing DM but also, increases their collective risk for CVD. In treating DM,
      involvement of the entire family, not only improves the care of the DM individual
      but also, helps to prevent the risk of developing DM in the family members. 

PMID- 24920931
TI  - Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose.
AB  - OBJECTIVE: Type 1 and 2 diabetes are characterized by elevated blood glucose
      levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum.
      However, previous studies reported a negative correlation between glucose
      concentrations and DPP4 levels. The purpose of this study was to elucidate the
      connection between glucose and DPP4 in adipocytes under physiological and
      diabetic conditions, because DPP4 is an adipokine. METHODS: Blood glucose and
      serum DPP4 levels were measured, and adipocytes were collected from mice under
      normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were
      incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1
      preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from
      mice and 3T3-L1 were stimulated by tumor necrosis factor-alpha (TNF-alpha) for 24
      hours. The levels of released and intracellular DPP4 were determined by enzyme
      linked immunosorbent assay. RESULTS: Mice fed high-fat diet had lower serum DPP4
      levels in the first and second week than controls. However, this difference
      gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes
      under 25 mM glucose produced lower DPP4 levels than those differentiated under
      5.5 mM; this was also observed in isolated adipocytes from mice. However, these
      effects of glucose were lost in adipocytes from diabetic mice, and an increase in
      total DPP4 levels was observed. The stimulation of adipocytes with TNF-alpha
      increased the release of DPP4 irrespective of glucose concentration. CONCLUSION:
      The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose
      under physiological conditions, but not in diabetic mice. Our results suggest
      that the observed increase in serum DPP4 levels may be attributed to increased
      production of DPP4 in adipocytes and an enhancement in TNF-alpha-induced release.

PMID- 24920930
TI  - Importance of cardiovascular disease risk management in patients with type 2
      diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is commonly accompanied by other cardiovascular
      disease (CVD) risk factors, such as hypertension, obesity, and dyslipidemia.
      Furthermore, CVD is the most common cause of death in people with T2DM. It is
      therefore of critical importance to minimize the risk of macrovascular
      complications by carefully managing modifiable CVD risk factors in patients with
      T2DM. Therapeutic strategies should include lifestyle and pharmacological
      interventions targeting hyperglycemia, hypertension, dyslipidemia, obesity,
      cigarette smoking, physical inactivity, and prothrombotic factors. This article
      discusses the impact of modifying these CVD risk factors in the context of T2DM;
      the clinical evidence is summarized, and current guidelines are also discussed.
      The cardiovascular benefits of smoking cessation, increasing physical activity,
      and reducing low-density lipoprotein cholesterol and blood pressure are well
      established. For aspirin therapy, any cardiovascular benefits must be balanced
      against the associated bleeding risk, with current evidence supporting this
      strategy only in certain patients who are at increased CVD risk. Although
      overweight, obesity, and hyperglycemia are clearly associated with increased
      cardiovascular risk, the effect of their modification on this risk is less well
      defined by available clinical trial evidence. However, for glucose-lowering
      drugs, further evidence is expected from several ongoing cardiovascular outcome
      trials. Taken together, the evidence highlights the value of early intervention
      and targeting multiple risk factors with both lifestyle and pharmacological
      strategies to give the best chance of reducing macrovascular complications in the
      long term. 

PMID- 24920932
TI  - Use of tazarotene foam for the treatment of acne vulgaris.
AB  - Acne vulgaris is a common inflammatory chronic disease of the pilosebaceous unit.
      It often requires long-term treatment, resulting in increased demand for topical
      medications that are popular with patients in order to achieve long-term
      compliance. Tazarotene foam 0.1% is a novel formulation of tazarotene. We review
      efficacy and tolerability studies of the new formulation, and suggest a possible
      place for the product in the management of acne vulgaris. 

PMID- 24920933
TI  - Predictability of the individual clinical outcome of extracorporeal shock wave
      therapy for cellulite.
AB  - BACKGROUND: Extracorporeal shock wave therapy has been successfully introduced
      for the treatment of cellulite in recent years. However, it is still unknown
      whether the individual clinical outcome of cellulite treatment with
      extracorporeal shock wave therapy can be predicted by the patient's individual
      cellulite grade at baseline, individual patient age, body mass index (BMI),
      weight, and/or height. METHODS: Fourteen Caucasian females with cellulite were
      enrolled in a prospective, single-center, randomized, open-label Phase II study.
      The mean (+/- standard error of the mean) cellulite grade at baseline was 2.5+/
      0.09 and mean BMI was 22.8+/-1.17. All patients were treated with radial
      extracorporeal shock waves using the Swiss DolorClast((r)) device (Electro
      Medical Systems, S.A., Nyon, Switzerland). Patients were treated unilaterally
      with 2 weekly treatments for 4 weeks on a randomly selected side (left or right),
      totaling eight treatments on the selected side. Treatment was performed at 3.5
      4.0 bar, with 15,000 impulses per session applied at 15 Hz. Impulses were
      homogeneously distributed over the posterior thigh and buttock area (resulting in
      7,500 impulses per area). Treatment success was evaluated after the last
      treatment and 4 weeks later by clinical examination, photographic documentation,
      contact thermography, and patient satisfaction questionnaires. RESULTS: The mean
      cellulite grade improved from 2.5+/-0.09 at baseline to 1.57+/-0.18 after the
      last treatment (ie, mean delta-1 was 0.93 cellulite grades) and 1.68+/-0.16 at
      follow-up (ie, mean delta-2 was 0.82 cellulite grades). Compared with baseline,
      no patient's condition worsened, the treatment was well tolerated, and no
      unwanted side effects were observed. No statistically significant (ie, P<0.05)
      correlation was found between individual values for delta-1 and delta-2 and
      cellulite grade at baseline, BMI, weight, height, or age. CONCLUSION: Radial
      shock wave therapy is a safe and effective treatment option for cellulite. The
      individual clinical outcome cannot be predicted by the patient's individual
      cellulite grade at baseline, BMI, weight, height, or age.

PMID- 24920936
TI  - Satisfaction and health-related quality of life in women with heavy menstrual
      bleeding; results from a non-interventional trial of the levonorgestrel-releasing
      intrauterine system or conventional medical therapy.
AB  - PURPOSE: To evaluate the patient satisfaction and health related quality of life
      (HRQoL) for levonorgestrel-releasing intrauterine system (LNG-IUS) versus
      conventional medical treatments ([CMTs] combined oral contraceptives, oral
      progestins, and antifibrinolytics, alone or in combination) in Asian women with
      heavy menstrual bleeding (HMB). PATIENTS AND METHODS: A total of 647 patients
      diagnosed with HMB were recruited to this non-interventional study from the eight
      participating countries in Asia. Patient satisfaction was recorded at the last
      visit (at 12 months or premature discontinuation). At each visit (at 3, 6, and 12
      months), patients completed the menorrhagia multi-attribute scale (MMAS) to
      assess HRQoL. RESULTS: A total of 83.5% of patients on the LNG-IUS were "very
      satisfied" or at least "satisfied" with the therapeutic effect of HMB treatment,
      compared with 59.2% of patients with CMTs (P<0.05). The mean (+/- standard
      deviation) MMAS score increased from 41.4+/-24.5 to 87.7+/-21.4 in the LNG-IUS
      arm, and from 44.1+/-24.9 to 73.1+/-25.3 in the CMTs arm. This increase was
      significantly higher in patients on the LNG-IUS, as compared with those on CMTs
      (P<0.05). The improvement in HRQoL in both treatment groups correlated with the
      body mass index of the patient, with larger improvement obtained in women with a
      higher body mass index. CONCLUSION: The majority of women using the LNG-IUS or
      CMTs for HMB were satisfied with their treatment, and both treatment modalities
      were associated with significant improvements in HRQoL over time. The improvement
      was greater with the LNG-IUS, compared with CMTs.

PMID- 24920935
TI  - Clinical epidemiology of epithelial ovarian cancer in the UK.
AB  - Epithelial ovarian cancer is the fifth commonest cancer among women and the
      leading cause of gynecological cancer death in the UK. Most women present with
      advanced disease, mainly because the nonspecific nature of the symptoms lead to
      diagnostic delays. Recent data have shown a fall in ovarian cancer mortality
      rates in the UK, but rates are still higher when compared to other European
      countries or the USA. In addition, surgeons in the UK achieve on average lower
      optimal surgical cytoreduction rates in patients with advanced ovarian cancer.
      Despite a wealth of information on epidemiological risk factors, the pathogenesis
      of epithelial ovarian cancer remains largely unknown. This review presents the
      most recent data on incidence, mortality, and survival for epithelial ovarian
      cancer in the UK. Time trends, trends by age, international comparisons, and
      regional variation in incidence, survival, and mortality are presented within the
      context of a major reorganization of cancer services that took place in the UK
      over 10 years ago. Centralization of cancer services has meant that women with
      ovarian cancer receive treatment in specialist Cancer Centers. 

PMID- 24920934
TI  - Pain control following inguinal herniorrhaphy: current perspectives.
AB  - Inguinal hernia repair is one of the most common surgeries performed worldwide.
      With the success of modern hernia repair techniques, recurrence rates have
      significantly declined, with a lower incidence than the development of chronic
      postherniorrhaphy inguinal pain (CPIP). The avoidance of CPIP is arguably the
      most important clinical outcome and has the greatest impact on patient
      satisfaction, health care utilization, societal cost, and quality of life. The
      etiology of CPIP is multifactorial, with overlapping neuropathic and nociceptive
      components contributing to this complex syndrome. Treatment is often challenging,
      and no definitive treatment algorithm exists. Multidisciplinary management of
      this complex problem improves outcomes, as treatment must be individualized.
      Current medical, pharmacologic, interventional, and surgical management
      strategies are reviewed. 

PMID- 24920937
TI  - Brachytherapy in the treatment of cervical cancer: a review.
AB  - Dramatic advances have been made in brachytherapy for cervical cancer. Radiation
      treatment planning has evolved from two-dimensional to three-dimensional,
      incorporating magnetic resonance imaging and/or computed tomography into the
      treatment paradigm. This allows for better delineation and coverage of the tumor,
      as well as improved avoidance of surrounding organs. Consequently, advanced
      brachytherapy can achieve very high rates of local control with a reduction in
      morbidity, compared with historic approaches. This review provides an overview of
      state-of-the-art gynecologic brachytherapy, with a focus on recent advances and
      their implications for women with cervical cancer. 

PMID- 24920938
TI  - Key determinants of induced abortion in women seeking postabortion care in
      hospital facilities in Ouagadougou, Burkina Faso.
AB  - INTRODUCTION: Despite the universal recognition of unsafe abortion as a major
      public health problem, very little research has been conducted to document its
      precipitating factors in Burkina Faso. Our aim was to investigate the key
      determinants of induced abortion in a sample of women who sought postabortion
      care. MATERIALS AND METHODS: A cross-sectional household survey was carried out
      from February to September 2012 in Ouagadougou, Burkina Faso. Data of 37 women
      who had had an induced abortion and 267 women who had had a spontaneous abortion
      were prospectively collected on sociodemographic characteristics, pregnancy and
      birth history, abortion experience, including previous abortion experience, and
      selected clinical information, including the type of abortion. A two-step
      regression analysis consisting of a univariate and a multivariate logistic
      regression was run on Stata version 11.2 in order to identify the key
      determinants of induced abortion. RESULTS: The findings indicated that 12% of all
      abortions were certainly induced. Three key factors were significantly and
      positively associated with the probability of having an induced abortion: whether
      the woman reported that her pregnancy was unwanted (odds ratio [OR] 10.45, 95%
      confidence interval [CI] 3.59-30.41); whether the woman reported was living in a
      household headed by her parents (OR 6.83, 95% CI 2.42-19.24); and if the woman
      reported was divorced or widowed (OR 3.47, 95% CI 1.08-11.10). On the contrary,
      being married was protective against induced abortion, with women who reported
      being married having an 83% (OR 0.17, CI 0.03-0.89) lower chance of having an
      induced abortion, even when the pregnancy was unwanted. CONCLUSION: This study
      has identified three major determinants of induced abortion in Ouagadougou,
      Burkina Faso. Improved targeted programs on family planning counseling, methods
      of contraception, and availability of contraceptives should be widely promoted.

PMID- 24920939
TI  - Rationale, design, and cohort enrolment of a prospective observational study of
      the clinical performance of the new contraceptive implant (Femplant) in Pakistan.
AB  - INTRODUCTION: The use of hormonal implants has gained positive traction in family
      planning programs in recent times. Compared to other popular methods, such as
      long-term reversible intrauterine devices, the use of hormonal implants as a
      family planning method has distinct advantages in terms of long-term efficiency
      and better user compliance and availability. This paper presents a study protocol
      to document and evaluate the efficacy, safety, and acceptability of Femplant
      (contraceptive implant) in Pakistan during the first year of its use among
      married women of reproductive age (18-44 years) at clinics in two provinces of
      Pakistan (Sindh and Punjab). MATERIALS AND METHODS: A total of 724 married women
      were enrolled in a noncomparative prospective observational study. The study
      involved six government clinics from the Population Welfare Department in Sindh
      Province and 13 clinics run by the Marie Stopes Society (a local nongovernmental
      organization) in both provinces. The participation of women was subject to
      voluntary acceptance and medical eligibility. All respondents were interviewed at
      baseline and subsequently at each scheduled visit during the study period. Side
      effects, complications and adverse events, if any, were recorded for every
      participant at each visit to the facility. DISCUSSION: Over the next 5-year
      period (2013-2018), 27 million hormonal implants will be made available in lower-
      to middle-income countries by international donors and agencies. The evidence
      generated from this study will identify factors affecting the acceptability and
      satisfaction of end users with Femplant (Sino-implant II). This will help to
      guide policies to enhance access to and the use of long-acting contraceptive
      implants in Pakistan and similar developing countries.

PMID- 24920940
TI  - Critical evaluation of stents in the peripheral arterial disease of the
      superficial femoral artery - focus on the paclitaxel eluting stent.
AB  - The endovascular management of obstructive disease of the superficial femoral
      artery (SFA) is challenging due to unique anatomical and biomechanical forces.
      Obstructive lesions of the SFA make up the largest proportion of lesions leading
      to symptomatic peripheral arterial disease. Accordingly, endovascular treatment
      of SFA disease is becoming increasingly common and, in many cases, is the
      preferred initial therapy. The use of self-expanding nitinol stents have proven
      superior to percutaneous transluminal balloon angioplasty in the treatment of
      intermediate length SFA stenosis. However, achieving durable results, as well as
      attaining adequate therapy for long occlusions typically seen in clinical
      practice, remains problematic. Newer technologies, such as paclitaxel eluting
      stents, seem promising in improving outcomes. 

PMID- 24920941
TI  - Obstructive sleep apnea and psychomotor vigilance task performance.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent disorder with
      considerable morbidity and mortality. Vigilance and attentiveness are often
      impaired in OSA patients. In occupational medicine settings, subjective reports
      of sleepiness are notoriously inaccurate, making the identification of objective
      measures of vigilance potentially important for risk assessments of fitness for
      duty. In order to evaluate the effects of OSA on attentiveness and vigilance, we
      conducted a cross-sectional study to examine the association between OSA and
      psychomotor vigilance task (PVT) performance. METHODS: Patients attending sleep
      clinics for evaluation of possible sleep apnea were recruited. The subjects
      underwent either a standard overnight laboratory polysomnography or home sleep
      study. Subjective daytime sleepiness was assessed by Epworth sleepiness scale,
      and vigilance was tested using a portable device. The participants were asked to
      respond to the PVT signals using their dominant hand. Each PVT administration
      lasted 10 minutes, with stimuli signals appearing randomly at variable intervals
      of 2-10 seconds. RESULTS: Mean age of the participants was 46+/-15 years, and
      mean body mass index was 34.3+/-9.8 kg/m(2). Participants with higher Epworth
      scores had worse PVT performance (P<0.05). In multivariate analyses, age, body
      mass index, and poor sleep efficiency (measured by Pittsburgh sleep quality index
      score) were associated with worse PVT performance (P<0.05). In contrast, PVT
      performance did not differ significantly across categories of apnea hypopnea
      index severity. Subgroup analysis demonstrated that women had worse performance
      on all PVT measures (P<0.05). CONCLUSION: PVT performance can be utilized for
      risk assessments of sleepiness and may be particularly useful among populations
      where subjective reports are unreliable.

PMID- 24920942
TI  - Influence of the timing of administration of crystalloid on maternal hypotension
      during spinal anesthesia for cesarean delivery: preload versus coload.
AB  - BACKGROUND: Prophylactic fluid preloading before spinal anesthesia has been a
      routine procedure to prevent maternal hypotension during cesarean delivery.
      Unlike colloid, timing of infusion of crystalloid may be important because of its
      short stay in intravascular space. We hypothesized that crystalloid loading just
      after intrathecal injection compared to preload would be more effective in
      preventing maternal hypotension. METHODS: In this prospective controlled study,
      sixty parturients were randomized to receive 15 ml/kg of crystalloid before
      (preload group) or after (coload group) intrathecal drug injection for spinal
      anesthesia. Hypotension was defined if systolic arterial pressure decreased below
      80% of baseline and ephedrine was administered to treat hypotension. The
      incidence of hypotension and the total dose of ephedrine were checked. Blood
      pressure, heart rate and nausea before childbirth were assessed. Neonatal
      outcomes were evaluated with Apgar scores and umbilical blood gas analysis.
      RESULTS: The incidence of hypotension was lower in the coload group compared to
      the preload group (53% vs. 83%, P = 0.026). The blood pressure showed the bigger
      drop during spinal anesthesia in the preload group (34 +/- 13 vs. 25 +/- 10 mmHg,
      P = 0.002) and smaller dose of ephedrine was required in the coload group (7.5 [0
      30] vs. 15 [0-40] mg, P = 0.015). The incidence of nausea was also lower in the
      coload group (27% vs. 60%, P = 0.019). Neonatal outcome measures were comparable
      between two groups. CONCLUSIONS: In case of using crystalloids for cesarean
      delivery, coload is more effective than preload for the prevention of maternal
      hypotension after spinal anesthesia. TRIAL REGISTRATION: Clinical Research
      Information Service KCT0000324 (Jan 12(th), 2012).

PMID- 24920943
TI  - Chemokines in the balance: maintenance of homeostasis and protection at CNS
      barriers.
AB  - In the adult central nervous system (CNS), chemokines and their receptors are
      involved in developmental, physiological and pathological processes. Although
      most lines of investigation focus on their ability to induce the migration of
      cells, recent studies indicate that chemokines also promote cellular interactions
      and activate signaling pathways that maintain CNS homeostatic functions. Many
      homeostatic chemokines are expressed on the vasculature of the blood brain
      barrier (BBB) including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell
      expression of these chemokines is known to regulate the entry of leukocytes into
      the CNS during immunosurveillance, new data indicate that CXCL12 is also involved
      in diverse cellular activities including adult neurogenesis and neuronal
      survival, having an opposing role to the homeostatic chemokine, CXCL14, which
      appears to regulate synaptic inputs to neural precursors. Neuronal expression of
      CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and
      communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12
      is unique in that it may regulate its own expression levels via binding to its
      scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of
      these and other homeostatic chemokines expressed within the CNS, including the
      possible implications of their dysfunction as a cause of neurologic disease. 

PMID- 24920944
TI  - The intergenerational multiple deficit model and the case of dyslexia.
AB  - Which children go on to develop dyslexia? Since dyslexia has a multifactorial
      etiology, this question can be restated as: what are the factors that put
      children at high risk for developing dyslexia? It is argued that a useful
      theoretical framework to address this question is Pennington's (2006) multiple
      deficit model (MDM). This model replaces models that attribute dyslexia to a
      single underlying cause. Subsequently, the generalist genes hypothesis for
      learning (dis)abilities (Plomin and Kovas, 2005) is described and integrated with
      the MDM. Next, findings are presented from a longitudinal study with children at
      family risk for dyslexia. Such studies can contribute to testing and specifying
      the MDM. In this study, risk factors at both the child and family level were
      investigated. This led to the proposed intergenerational MDM, in which both
      parents confer liability via intertwined genetic and environmental pathways.
      Future scientific directions are discussed to investigate parent-offspring
      resemblance and transmission patterns, which will shed new light on disorder
      etiology. 

PMID- 24920945
TI  - Contingent capture of involuntary visual attention interferes with detection of
      auditory stimuli.
AB  - The involuntary capture of attention by salient visual stimuli can be influenced
      by the behavioral goals of an observer. For example, when searching for a target
      item, irrelevant items that possess the target-defining characteristic capture
      attention more strongly than items not possessing that feature. Such contingent
      capture involves a shift of spatial attention toward the item with the target
      defining characteristic. It is not clear, however, if the associated decrements
      in performance for detecting the target item are entirely due to involuntary
      orienting of spatial attention. To investigate whether contingent capture also
      involves a non-spatial interference, adult observers were presented with streams
      of visual and auditory stimuli and were tasked with simultaneously monitoring for
      targets in each modality. Visual and auditory targets could be preceded by a
      lateralized visual distractor that either did, or did not, possess the target
      defining feature (a specific color). In agreement with the contingent capture
      hypothesis, target-colored distractors interfered with visual detection
      performance (response time and accuracy) more than distractors that did not
      possess the target color. Importantly, the same pattern of results was obtained
      for the auditory task: visual target-colored distractors interfered with sound
      detection. The decrement in auditory performance following a target-colored
      distractor suggests that contingent capture involves a source of processing
      interference in addition to that caused by a spatial shift of attention.
      Specifically, we argue that distractors possessing the target-defining
      characteristic enter a capacity-limited, serial stage of neural processing, which
      delays detection of subsequently presented stimuli regardless of the sensory
      modality. 

PMID- 24920946
TI  - Diagnostic tools of pleural effusion.
AB  - Pleural effusion is not a rare disease in Korea. The diagnosis of pleural
      effusion is very difficult, even though the patients often complain of typical
      symptoms indicating of pleural diseases. Pleural effusion is characterized by the
      pleural cavity filled with transudative or exudative pleural fluids, and it is
      developed by various etiologies. The presence of pleural effusion can be
      confirmed by radiological studies including simple chest radiography,
      ultrasonography, or computed tomography. Identifying the causes of pleural
      effusions by pleural fluid analysis is essential for proper treatments. This
      review article provides information on the diagnostic approaches of pleural
      effusions and further suggested ways to confirm their various etiologies, by
      using the most recent journals for references. 

PMID- 24920947
TI  - Malignant pleural effusion: medical approaches for diagnosis and management.
AB  - Malignant pleural effusions (MPEs) are the second leading cause of exudative
      pleural effusions after parapneumonic effusions. In the vast majority of cases, a
      MPE signifies incurable disease associated with high morbidity and mortality.
      Considerable advances have been made for the diagnosis of MPEs, through the
      development of improved methods in the specialized cytological and imaging
      studies. The cytological or histological confirmation of malignant cells is
      currently important in establishing a diagnosis. Furthermore, despite major
      advancements in cancer treatment for the past two decades, management of MPE
      remains palliative. This article presents a comprehensive review of the medical
      approaches for diagnosis and management of MPE. 

PMID- 24920948
TI  - Progression-free survival: an important prognostic marker for long-term survival
      of small cell lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is an extremely aggressive tumor with a
      poor clinical course. Although many efforts have been made to improve patients'
      survival rates, patients who survive longer than 2 years after chemotherapy are
      still very rare. We examined the baseline characteristics of patients with long
      term survival rates in order to identify the prognostic factors for overall
      survivals. METHODS: A total of 242 patients with cytologically or histologically
      diagnosed SCLC were enrolled into this study. The patients were categorized into
      long- and short-term survival groups by using a survival cut-off of 2 years after
      diagnosis. Cox's analyses were performed to identify the independent factors.
      RESULTS: The mean patient age was 65.66 years, and 85.5% were males; among the
      patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate
      analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06;
      p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression
      free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent
      prognostic markers for poor survival rates. CONCLUSION: In addition to other well
      known prognostic factors, this study discovered relationships between the long
      term survival rates and serum CRP levels, TNM staging, and PFS. In situations
      with unfavorable conditions, the PFS would be particularly helpful for managing
      SCLC patients.

PMID- 24920949
TI  - Influence of environmental exposures on patients with chronic obstructive
      pulmonary disease in Korea.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      airflow limitation and results from environmental factors and genetic factors.
      Although cigarette smoking is a major risk factor, other environmental exposures
      can influence COPD. The purpose of this study is to investigate the clinical
      characteristics of COPD according to the history of environmental exposure.
      METHODS: The study population comprised of 347 subjects with COPD who were
      recruited from the pulmonary clinics of 14 hospitals within the Korean
      Obstructive Lung Disease Study Group. We classified environmental exposures
      according to history of living near factory, and direct exposure history to
      firewood or briquette. According to living environmental exposures, we compared
      the frequency of respiratory symptoms, pulmonary function, quality of life,
      exercise capacity, and computed tomography phenotypes. RESULTS: Thirty-one
      subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure
      history to briquette, and 184 (53.3%) had exposure history to firewood. Patients
      with history of living near a factory had a significantly longer duration of
      sputum, while patients with exposure to firewood tended to have lower forced
      expiratory volume in one second, and patients with exposure to briquette tended
      to have lower six minute walk distance. CONCLUSION: COPD subjects with the
      history of living near factory had more frequent respiratory symptoms such as
      sputum. Our data suggest that environmental exposure may influence clinical
      phenotype of COPD.

PMID- 24920950
TI  - A case of catamenial hemoptysis treated by bronchial artery embolization.
AB  - Catamenial hemoptysis is a rare condition, characterized by recurrent hemoptysis
      associated with the presence of intrapulmonary or endobronchial endometrial
      tissue. Therapeutic strategies proposed for intrapulmonary endometriosis with
      catamenial hemoptysis consist of medical treatments and surgery. Bronchial artery
      embolization is a well-established modality in the management of massive or
      recurrent hemoptysis, but has seldom been used for the treatment of catamenial
      hemoptysis. We report a case of catamenial hemoptysis associated with pulmonary
      parenchymal endometriosis, which was successfully treated by a bronchial artery
      embolization. 

PMID- 24920951
TI  - Tracheobronchial polyps following thermal inhalation injury.
AB  - The early pulmonary consequences of inhalation injury are well documented;
      however, little is known about delayed pulmonary complications following thermal
      inhalation injury. Although thermal injury below the vocal cords is rare because
      of effective heat dissipation in the upper airway, inflammatory endobronchial
      polyps have previously been reported as a delayed complication associated with
      inhalation injury. We report an extraordinary case of tracheobronchial polyps in
      patients with smoke inhalation injury. This report shows the delayed development
      and natural course of tracheobronchial polyps following thermal injury. 

PMID- 24920952
TI  - Pancreaticothoracic fistula presenting with hemoptysis and pneumothorax in a
      chronic alcoholic patient.
AB  - Pancreaticothoracic fistula is a rare complication of acute or chronic alcoholic
      pancreatitis. It may present with various symptoms, like dyspnea, abdominal pain,
      cough, chest pain, fever, back pain, hemoptysis, fatigue, or orthopnea.
      Pancreaticothoracic fistula can be detected by magnetic resonance
      cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography
      (ERCP), or computed tomography. MRCP has high sensitivity and fewer side effects,
      and thus it has recently been recommended as the first choice for the detection
      of pancreaticothoracic fistula. On the other hand, ERCP enables the detection and
      treatment of pancreaticothoracic fistula and allows for stent insertion; for this
      reason it is a commonly used modality in pancreaticothoracic fistula cases.
      Herein, the authors describe a case of pancreaticothoracic fistula detected by
      ERCP and MRCP that manifested only respiratory symptoms, namely hemoptysis and
      pneumothorax without abdominal pain, which commonly accompanies pancreatitis. 

PMID- 24920953
TI  - Multidrug-Resistant Tuberculosis Presenting as Miliary Tuberculosis without
      Immune Suppression: A Case Diagnosed Rapidly with the Genotypic Line Probe Assay
      Method.
AB  - Miliary tuberculosis (TB) is a rare extrapulmonary form of TB, and there have
      been only two reports of miliary TB associated with infection with multidrug
      resistant (MDR)-TB pathogen in an immunocompetent host. A 32-year-old woman was
      referred to our hospital because of abnormal findings on chest X-ray. The patient
      was diagnosed with MDR-TB by a line probe assay and was administered proper
      antituberculous drugs. After eight weeks, a solid-media drug sensitivity test
      revealed that the pathogen was resistant to ethambutol and streptomycin in
      addition to isoniazid and rifampicin. The patient was then treated with effective
      antituberculous drugs without delay after diagnosis of MDR-TB. To the best of our
      knowledge, this is the first case of miliary TB caused by MDR-TB pathogen in
      Korea. 

PMID- 24920954
TI  - Co-infection with Influenza: Do Not Forget Aspergillus in the Immunosuppressed
      Neutropenic Host.

PMID- 24920955
TI  - An analysis of early developmental trauma in social anxiety disorder and
      posttraumatic stress disorder.
AB  - BACKGROUND: The early contributions of childhood trauma (emotional, physical,
      sexual, and general) have been hypothesized to play a significant role in the
      development of anxiety disorders, such as posttraumatic stress disorder (PTSD)
      and social anxiety disorder (SAD). The aim of this study was to assess childhood
      trauma differences between PTSD and SAD patients and healthy controls, as
      measured by the Early Trauma Inventory. METHODS: We examined individuals (N =
      109) with SAD with moderate/severe early developmental trauma (EDT) (n = 32),
      individuals with SAD with low/no EDT (n = 29), individuals with PTSD with EDT (n
      = 17), and healthy controls (n = 31). The mean age was 34 years (SD = 11).
      Subjects were screened with the Mini-International Neuropsychiatric Interview
      (MINI), Liebowitz Social Anxiety Scale (LSAS), Clinician-Administered PTSD Scale
      (CAPS), and Childhood Trauma Questionnaire (CTQ). Analysis of variance was
      performed to assess group differences. Correlations were calculated between
      childhood traumas. RESULTS: Although not statistically significant, individuals
      with PTSD endorsed more physical and sexual childhood trauma compared with
      individuals with SAD with moderate/severe EDT who endorsed more emotional trauma.
      For all groups, physical and emotional abuse occurred between ages 6 and 11,
      while the occurrence of sexual abuse in individuals with PTSD was at 6-11 years
      and later (13-18 years) in individuals with SAD with moderate/severe EDT. For
      emotional abuse in all groups, the perpetrator was mostly a primary female
      caregiver; for sexual abuse, it was mostly a nonfamilial adult male, while for
      physical abuse, it was mostly a caregiver (male in PTSD and female in SAD with
      moderate/severe EDT). CONCLUSIONS: The contribution of childhood abuse to the
      development of PTSD and SAD and the differences between these groups and other
      anxiety disorders should not be ignored and attention should be given to the
      frequency and severity of these events. The relationship of the perpetrator(s)
      and the age of onset of childhood abuse are also important considerations as they
      provide a useful starting point to assess impact over the life course. This can,
      in turn, guide clinicians on the optimal timing for the delivery of interventions
      for the prevention of PTSD and SAD.

PMID- 24920956
TI  - An Enduring Somatic Threat Model of Posttraumatic Stress Disorder Due to Acute
      Life-Threatening Medical Events.
AB  - Posttraumatic stress disorder (PTSD) occurs in 12-25% of survivors of acute life
      threatening medical events such as heart attack, stroke, and cancer, and is
      associated with recurrence of cardiac events and mortality in heart attack
      survivors. This article reviews the current state of knowledge about PTSD after
      such events, and proposes an Enduring Somatic Threat (EST) model of PTSD due to
      acute life-threatening medical events to address underappreciated differences
      between PTSD due to past, discrete/external traumatic events (such as combat) and
      PTSD due to acute manifestations of chronic disease that are enduring/internal in
      nature (such as heart attack and stroke). The differences include the external
      versus internal/somatic source of the threat, the past versus present/future
      temporal focus of threatening cognitions, the different types and consequences of
      avoidance behavior, and the different character and consequences of hyperarousal.
      Although important differences between the two types of PTSD exist, the EST model
      proposes that the underlying fear of mortality maintains PTSD symptoms due to
      both discrete/external and ongoing/somatic events. Finally, this article offers a
      research agenda for testing the EST model, with a particular focus on areas that
      may improve cardiovascular prognosis and health behaviors in survivors of heart
      attack and stroke.

PMID- 24920957
TI  - Superior triacylglycerol (TAG) accumulation in starchless mutants of Scenedesmus
      obliquus: (I) mutant generation and characterization.
AB  - BACKGROUND: Microalgae are a promising platform for producing neutral lipids, to
      be used in the application for biofuels or commodities in the feed and food
      industry. A very promising candidate is the oleaginous green microalga
      Scenedesmus obliquus, because it accumulates up to 45% w/w triacylglycerol (TAG)
      under nitrogen starvation. Under these conditions, starch is accumulated as well.
      Starch can amount up to 38% w/w under nitrogen starvation, which is a substantial
      part of the total carbon captured. When aiming for optimized TAG production,
      blocking the formation of starch could potentially increase carbon allocation
      towards TAG. In an attempt to increase TAG content, productivity and yield,
      starchless mutants of this high potential strain were generated using UV
      mutagenesis. Previous studies in Chlamydomonas reinhardtii have shown that
      blocking the starch synthesis yields higher TAG contents, although these TAG
      contents do not surpass those of oleaginous microalgae yet. So far no starchless
      mutants in oleaginous green microalgae have been isolated that result in higher
      TAG productivities. RESULTS: Five starchless mutants have been isolated
      successfully from over 3,500 mutants. The effect of the mutation on biomass and
      total fatty acid (TFA) and TAG productivity under nitrogen-replete and nitrogen
      depleted conditions was studied. All five starchless mutants showed a decreased
      or completely absent starch content. In parallel, an increased TAG accumulation
      rate was observed for the starchless mutants and no substantial decrease in
      biomass productivity was perceived. The most promising mutant showed an increase
      in TFA productivity of 41% at 4 days after nitrogen depletion, reached a TAG
      content of 49.4% (% of dry weight) and had no substantial change in biomass
      productivity compared to the wild type. CONCLUSIONS: The improved S. obliquus TAG
      production strains are the first starchless mutants in an oleaginous green
      microalga that show enhanced TAG content under photoautotrophic conditions. These
      results can pave the way towards a more feasible microalgae-driven TAG production
      platform.

PMID- 24920958
TI  - Effects of agitation on particle-size distribution and enzymatic hydrolysis of
      pretreated spruce and giant reed.
AB  - BACKGROUND: Mixing is an energy demanding process which has been previously shown
      to affect enzymatic hydrolysis. Concentrated biomass slurries are associated with
      high and non-Newtonian viscosities and mixing in these systems is a complex task.
      Poor mixing can lead to mass and/or heat transfer problems as well as
      inhomogeneous enzyme distribution, both of which can cause possible yield
      reduction. Furthermore the stirring energy dissipation may impact the particle
      size which in turn may affect the enzymatic hydrolysis. The objective of the
      current work was to specifically quantify the effects of mixing on particle-size
      distribution (PSD) and relate this to changes in the enzymatic hydrolysis. Two
      rather different materials were investigated, namely pretreated Norway spruce and
      giant reed. RESULTS: Changes in glucan hydrolysis and PSD were measured as a
      function of agitation during enzymatic hydrolysis at fiber loadings of 7 or 13%
      water-insoluble solids (WIS). Enzymatic conversion of pretreated spruce was
      strongly affected by agitation rates at the higher WIS content. However, at low
      WIS content the agitation had almost no effect on hydrolysis. There was some
      effect of agitation on the hydrolysis of giant reed at high WIS loading, but it
      was smaller than that for spruce, and there was no measurable effect at low WIS
      loading. In the case of spruce, intense agitation clearly affected the PSD and
      resulted in a reduced mean particle size, whereas for giant reed the decrease in
      particle size was mainly driven by enzymatic action. However, the rate of
      enzymatic hydrolysis was not increased after size reduction by agitation.
      CONCLUSIONS: The impact of agitation on the enzymatic hydrolysis clearly depends
      not only on feedstock but also on the solids loading. Agitation was found to
      affect the PSD differently for the examined pretreated materials spruce and giant
      reed. The fact that the reduced mean particle diameter could not explain the
      enhanced hydrolysis rates found for spruce at an elevated agitation suggests that
      mass transfer at sustained high viscosities plays an important role in
      determining the rate of enzymatic hydrolysis.

PMID- 24920960
TI  - Single-step bioconversion of lignocellulose to hydrogen using novel moderately
      thermophilic bacteria.
AB  - BACKGROUND: Consolidated bioprocessing (CBP) of lignocellulosic biomass to
      hydrogen offers great potential for lower cost and higher efficiency compared to
      processes featuring dedicated cellulase production. Current studies on CBP-based
      hydrogen production mainly focus on using the thermophilic cellulolytic bacterium
      Clostridium thermocellum and the extremely thermophilic cellulolytic bacterium
      Caldicellulosiruptor saccharolyticus. However, no studies have demonstrated that
      the strains in the genus Thermoanaerobacterium could be used as the sole
      microorganism to accomplish both cellulose degradation and H2 generation.
      RESULTS: We have specifically screened for moderately thermophilic cellulolytic
      bacteria enabling to produce hydrogen directly from conversion of lignocellulosic
      materials. Three new strains of thermophilic cellulolytic bacteria in the genus
      Thermoanaerobacterium growing at a temperature of 60 degrees C were isolated. All
      of them grew well on various plant polymers including microcrystalline cellulose,
      filter paper, xylan, glucose, and xylose. In particular, the isolated bacterium,
      designated as Thermoanaerobacterium thermosaccharolyticum M18, showed high
      cellulolytic activity and a high yield of H2. When it was grown in 0.5%
      microcrystalline cellulose, approximately 82% cellulose was consumed, and the H2
      yield and maximum production rate reached 10.86 mmol/g Avicel and 2.05 mmol/L/h,
      respectively. Natural lignocellulosic materials without any physicochemical or
      biological pretreatment also supported appreciable growth of strain M18, which
      resulted in 56.07% to 62.71% of insoluble cellulose and hemicellulose polymer
      degradation in corn cob, corn stalk, and wheat straw with a yield of 3.23 to 3.48
      mmol H2/g substrate and an average production rate of 0.10 to 0.13 mmol H2/L/h.
      CONCLUSIONS: The newly isolated strain T. thermosaccharolyticum M18 displayed
      effective degradation of lignocellulose and produced large amounts of hydrogen.
      This is the first report of a Thermoanaerobacterium species presenting
      cellulolytic characteristics, and this species thus represents a novel
      cellulolytic bacterium distinguished from all other known cellulolytic bacteria.
      In comparison, the extraordinary yield and specific rate of hydrogen for strain
      M18 obtained from lignocellulose make it more attractive in monoculture
      fermentation. T. thermosaccharolyticum M18 is thus a potential candidate for
      rapid conversion of lignocellulose to biohydrogen in a single step.

PMID- 24920959
TI  - Regulation of the cholesterol biosynthetic pathway and its integration with fatty
      acid biosynthesis in the oleaginous microalga Nannochloropsis oceanica.
AB  - BACKGROUND: Sterols are vital structural and regulatory components in eukaryotic
      cells; however, their biosynthetic pathways and functional roles in microalgae
      remain poorly understood. RESULTS: In the oleaginous microalga Nannochloropsis
      oceanica, the sterol biosynthetic pathway produces phytosterols as minor products
      and cholesterol as the major product. The evidence together with their deduced
      biosynthetic pathways suggests that N. oceanica exhibits features of both higher
      plants and mammals. Temporal tracking of sterol profiles and sterol-biosynthetic
      transcripts in response to changes in light intensity and nitrogen supply reveal
      that sterols play roles in cell proliferation, chloroplast differentiation, and
      photosynthesis. Furthermore, the dynamics of fatty acid (FA) and FA-biosynthetic
      transcripts upon chemical inhibitor-induced sterol depletion reveal possible co
      regulation of sterol production and FA synthesis, in that the squalene epoxidase
      inhibitor terbinafine reduces sterol content yet significantly elevates free FA
      production. Thus, a feedback regulation of sterol and FA homeostasis is proposed,
      with the 1-deoxy-D-xylulose 5-phosphate synthase (DXS, the committed enzyme in
      isoprenoid and sterol biosynthesis) gene potentially subject to feedback
      regulation by sterols. CONCLUSION: These findings reveal features of sterol
      function and biosynthesis in microalgae and suggest new genetic engineering or
      chemical biology approaches for enhanced oil production in microalgae.

PMID- 24920961
TI  - Semi-supervised consensus clustering for gene expression data analysis.
AB  - BACKGROUND: Simple clustering methods such as hierarchical clustering and k-means
      are widely used for gene expression data analysis; but they are unable to deal
      with noise and high dimensionality associated with the microarray gene expression
      data. Consensus clustering appears to improve the robustness and quality of
      clustering results. Incorporating prior knowledge in clustering process (semi
      supervised clustering) has been shown to improve the consistency between the data
      partitioning and domain knowledge. METHODS: We proposed semi-supervised consensus
      clustering (SSCC) to integrate the consensus clustering with semi-supervised
      clustering for analyzing gene expression data. We investigated the roles of
      consensus clustering and prior knowledge in improving the quality of clustering.
      SSCC was compared with one semi-supervised clustering algorithm, one consensus
      clustering algorithm, and k-means. Experiments on eight gene expression datasets
      were performed using h-fold cross-validation. RESULTS: Using prior knowledge
      improved the clustering quality by reducing the impact of noise and high
      dimensionality in microarray data. Integration of consensus clustering with semi
      supervised clustering improved performance as compared to using consensus
      clustering or semi-supervised clustering separately. Our SSCC method outperformed
      the others tested in this paper.

PMID- 24920962
TI  - Angiotensin II receptor blocker telmisartan attenuates aortic stiffening and
      remodelling in STZ-diabetic rats.
AB  - BACKGROUND: Prevention or attenuation of diabetic vascular complications includes
      anti-hypertensive treatment with renin-angiotensin system inhibitors on account
      of their protective effects beyond blood pressure reduction. The present study
      aimed to investigate the effects of telmisartan, an angiotensin II type 1
      receptor blocker (ARB), on blood pressure, aortic stiffening, and aortic
      remodelling in experimental type 1 diabetes in rats. METHODS: Diabetes was
      induced by streptozotocin (STZ) (65 mg/kg) in male Wistar rats. One diabetic
      group was treated for 10 weeks with telmisartan (10 mg/kg/day p/o). Pressure
      independent aortic pulse wave velocity (PWV) was measured under anaesthesia after
      intravenous infusion of phenylephrine and nitroglycerine. Aortic wall samples
      were collected for histomorphometrical analysis. RESULTS: Untreated diabetes
      imposed differential effects on aortic stiffening, as demonstrated by increased
      isobaric PWV over a range of high blood pressures, but not at lower blood
      pressures. This was associated with loss and disruption of elastin fibres and an
      increase in collagen fibres in the aortic media. Treatment with telmisartan
      decreased resting blood pressure, reduced aortic stiffness, and partially
      prevented the degradation of elastin network within the aortic wall. CONCLUSIONS:
      Telmisartan improved the structural and functional indices of aortic stiffening
      induced by untreated STZ-diabetes, demonstrating the importance of ARBs in the
      therapeutic approach to diabetic vascular complications.

PMID- 24920964
TI  - Depicting estimates using the intercept in meta-regression models: The moving
      constant technique.
AB  - In any scientific discipline, the ability to portray research patterns
      graphically often aids greatly in interpreting a phenomenon. In part to depict
      phenomena, the statistics and capabilities of meta-analytic models have grown
      increasingly sophisticated. Accordingly, this article details how to move the
      constant in weighted meta-analysis regression models (viz. "meta-regression") to
      illuminate the patterns in such models across a range of complexities. Although
      it is commonly ignored in practice, the constant (or intercept) in such models
      can be indispensible when it is not relegated to its usual static role. The
      moving constant technique makes possible estimates and confidence intervals at
      moderator levels of interest as well as continuous confidence bands around the
      meta-regression line itself. Such estimates, in turn, can be highly informative
      to interpret the nature of the phenomenon being studied in the meta-analysis,
      especially when a comparison with an absolute or a practical criterion is the
      goal. Knowing the point at which effect size estimates reach statistical
      significance or other practical criteria of effect size magnitude can be quite
      important. Examples ranging from simple to complex models illustrate these
      principles. Limitations and extensions of the strategy are discussed. Copyright
      (c) 2011 John Wiley & Sons, Ltd. 

PMID- 24920965
TI  - Lower-dose CT urography (CTU) with iterative reconstruction technique in children
      - initial experience and examination protocol.
AB  - BACKGROUND: Conventional X-ray urography is one of the basic imaging techniques
      in urinary tract diseases in children. CT urography (CTU) employing standard
      Filtered Back Projection (FBP) reconstruction algorithms is connected with higher
      radiation dose. Advanced iterative reconstruction techniques enable lowering the
      radiation dose to the level comparable with conventional X-ray urography with
      better visualization of the urinary tract. Study protocol and indications for
      this modified technique should be discussed. MATERIAL/METHODS: Introduction of
      iterative image reconstruction techniques allowed to significantly reduce the
      radiation dose delivered during examinations performed at our Department,
      including CT examinations of urinary tract in children. During the last two
      years, CT urography replaced conventional X-ray urography and became the basic
      imaging technique in our Department. We discuss the study protocol regarding
      pediatric CTU examinations. The main goal is to receive an optimal image quality
      at reduced radiation dose. RESULTS: CTU examinations performed using the standard
      filtered back projection (FBP) reconstruction technique are associated with
      radiation doses about 1.5 times higher than those in conventional X-ray
      urography. Implementation of iterative reconstruction algorithms in advanced CT
      scanners allow to reduce the radiation dose to a level comparable or even lower
      than that in X-ray urography. In addition, urinary tract can be evaluated more
      precisely in multiplanar reformatted (MPR) and volume rendered (VR) images.
      CONCLUSIONS: 1. Advanced iterative reconstruction techniques allow to reduce
      radiation dose in CT examinations and to extend indications for CT urography in
      children. 2. Urinary tract can be evaluated more precisely in multiplanar
      reformatted and volume rendered images. 3. CTU may replace conventional X-ray
      urography in children.

PMID- 24920963
TI  - Determinants of intensive insulin therapeutic regimens in patients with type 1
      diabetes: data from a nationwide multicenter survey in Brazil.
AB  - BACKGROUND: To evaluate the determinants of intensive insulin regimens (ITs) in
      patients with type 1 diabetes (T1D). METHODS: This multicenter study was
      conducted between December 2008 and December 2010 in 28 public clinics in 20
      Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1%
      Caucasian). Insulin regimens were classified as follows: group 1, conventional
      therapy (CT) (intermediate human insulin, one to two injections daily); group 2
      (three or more insulin injections of intermediate plus regular human insulin);
      group 3 (three or more insulin injections of intermediate human insulin plus
      short-acting insulin analogues); group 4, basal-bolus (one or two insulin
      injections of long-acting plus short-acting insulin analogues or regular
      insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion
      (CSII). Groups 2 to 5 were considered IT groups. RESULTS: We obtained complete
      data from 2,961 patients. Combined intermediate plus regular human insulin was
      the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by
      2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood
      glucose and were treated at the tertiary care level compared to CT patients (p <
      0.001). The majority of patients from all groups had HbA1c levels above the
      target. Overweight or obesity was not associated with insulin regimen. Logistic
      regression analysis showed that economic status, age, ethnicity, and level of
      care were associated with IT (p < 0.001). CONCLUSIONS: Given the prevalence of
      intensive treatment for T1D in Brazil, more effective therapeutic strategies are
      needed for long term-health benefits.

PMID- 24920966
TI  - Introducing IJTMB's Trigger Points: Topical Dialogue amongst Therapeutic Massage
      & Bodywork Practitioners and Educators.
AB  - The International Journal of Therapeutic Massage and Bodywork (IJTMB) has as its
      core a key interest in and mission to develop the practice of therapeutic massage
      and bodywork by contributing to the field's body of knowledge. The IJTMB
      Editorial Board understands that one's daily practice provides the initial
      testing ground for the development of practice-based knowledge and, ultimately,
      expertise. Consequently, this practice-based knowledge and experience provides
      fertile ground for research ideas that further refine our understanding and come
      full circle to enhance clinical efficacy. Ultimately, without discourse and
      knowledge transference, the possibility of growing the body of knowledge for
      therapeutic massage and bodywork or stimulating research in the field is lost. To
      facilitate discourse and transference of knowledge within the field of
      therapeutic massage and bodywork, the IJTMB is launching a new journal component
      entitled Trigger Points: Topical Dialogue amongst Therapeutic Massage & Bodywork
      Practitioners and Educators. The purpose of IJTMB's Trigger Points is to
      "trigger" the sharing and discussion of knowledge and expertise among therapeutic
      massage and bodywork practitioners, educators, and researchers about different
      approaches to treating specific conditions or addressing specific population
      issues. Each IJTMB issue, starting with this issue, will include a call for
      responses to the next Trigger Points topic. Publication of the results for each
      topic will be in the second issue after the initial call for submissions. With
      your participation, these IJTMB Trigger Points columns will spark dynamic
      dialogue, perhaps even collaborations, in the therapeutic massage and bodywork
      field across practitioners, educators, and researchers. 

PMID- 24920967
TI  - Assessing the effectiveness of massage therapy for bilateral cleft lip
      reconstruction scars.
AB  - BACKGROUND AND OBJECTIVE: Bilateral cleft lips occur when the bones that form the
      upper lip fail to fuse at birth. Surgical reconstruction creates scars, which may
      lead to the following impairments: adhesions, decreased oral range of motion,
      decreased strength of orbicularis oris muscle, and asymmetry of oral region
      leading to poor self-esteem. The purpose of this case study is to determine the
      effectiveness of massage therapy in its ability to improve these impairments.
      METHODS: A five-week treatment plan consisting of fascial release, kneading, and
      intraoral techniques. Subjective information was assessed on two scales:
      restriction of scar and clients attitudes and acceptance of scar. Objective
      information was cataloged through photographs, a palpatory chart, and a self
      created "Pen Test". RESULTS: Results included increase range of motion and
      strength, decrease restrictions (palpable and subjective), and increase of
      symmetry. Client's perceived confidence of scar and its appearance increased.
      CONCLUSIONS: The evidence suggests that massage therapy helped with the
      impairments associated with scars formed by bilateral cleft lip reconstruction.

PMID- 24920968
TI  - The Intersection of Massage Practice and Research: Community Massage Therapists
      as Research Personnel on an NIH-funded Effectiveness Study.
AB  - INTRODUCTION: Few NIH funded studies give community massage therapists the
      opportunity to become study personnel. A recent NIH/NCCAM-funded study
      investigating chronic low back pain (CLBP) recruited, trained, and utilized
      community massage practitioners (CMPs) as study personnel. This study's aim was
      to determine whether health-related outcomes for CLBP improve when patients are
      referred from primary care to select CAM modalities including massage therapy
      (MT). The purpose of this paper is to report the results of the study's three
      massage practice-driven study objectives which were to: 1) identify challenges
      and solutions to recruiting and retaining ample CMPs, 2) develop a practice
      informed protocol reflecting real-world MT, and 3) determine the extent to which
      CMPs comply with rigorous research methodology in their clinical practices as
      study personnel. METHODS: Eligible CMPs in urban and rural Kentucky counties were
      identified through licensure board records, professional organizations, and
      personal contact opportunities. Interested CMPs completed 6 CE hours of research
      and Human Subjects Protection training and agreed to comply with a study protocol
      reflecting MT as practiced. Once trained, study CMPs were matched with study
      participants to provide and document up to 10 MT sessions per participant.
      RESULTS: Utilizing prominent MT community members proved invaluable to CMP
      recruitment and protocol development. CMP recruitment challenges included mixed
      interest, low number of available rural CMPs, busy clinic schedules, and
      compensation. Ethics CE credits were offered to encourage CMP interest. A total
      of 28 Kentucky licensed massage therapists with 5-32 years of experience
      completed study training. A total of 127 CLBP patients consented to participate
      (n = 104 for MT). Twenty-five CMPs were assigned CLBP patients and provided 1-10
      treatments for 94 study participants. Treatment documentation was provided by
      CMPs for 97% of treatments provided. CONCLUSIONS: When recruitment, retention,
      and protocol compliance challenges are met, CMPs are valuable study personnel for
      practice-based research reflecting real-world MT practice.

PMID- 24920970
TI  - Quantitative trait locus analysis of resistance to panicle blast in the rice
      cultivar Miyazakimochi.
AB  - BACKGROUND: Rice blast is a destructive disease caused by Magnaporthe oryzae, and
      it has a large impact on rice production worldwide. Compared with leaf blast
      resistance, our understanding of panicle blast resistance is limited, with only
      one panicle blast resistance gene, Pb1, isolated so far. The japonica cultivar
      Miyazakimochi shows resistance to panicle blast, yet the genetic components
      accounting for this resistance remain to be determined. RESULTS: In this study,
      we evaluated the panicle blast resistance of populations derived from a cross
      between Miyazakimochi and the Bikei 22 cultivar, which is susceptible to both
      leaf and panicle blast. The phenotypic analyses revealed no correlation between
      panicle blast resistance and leaf blast resistance. Quantitative trait locus
      (QTL) analysis of 158 recombinant inbred lines using 112 developed genome-wide
      and 35 previously reported polymerase chain reaction (PCR) markers revealed the
      presence of two QTLs conferring panicle blast resistance in Miyazakimochi: a
      major QTL, qPbm11, on chromosome 11; and a minor QTL, qPbm9, on chromosome 9. To
      clarify the contribution of these QTLs to panicle blast resistance, 24 lines
      homozygous for each QTL were selected from 2,818 progeny of a BC2F7 backcrossed
      population, and characterized for disease phenotypes. The panicle blast
      resistance of the lines harboring qPbm11 was very similar to the resistant donor
      parental cultivar Miyazakimochi, whereas the contribution of qPbm9 to the
      resistance was small. Genotyping of the BC2F7 individuals highlighted the overlap
      between the qPbm11 region and a locus of the panicle blast resistance gene, Pb1.
      Reverse transcriptase PCR analysis revealed that the Pb1 transcript was absent in
      the panicles of Miyazakimochi, demonstrating that qPbm11 is a novel genetic
      component of panicle blast resistance. CONCLUSIONS: This study revealed that
      Miyazakimochi harbors a novel panicle blast resistance controlled mainly by the
      major QTL qPbm11. qPbm11 is distinct from Pb1 and could be a genetic source for
      breeding panicle blast resistance, and will improve understanding of the
      molecular basis of host resistance to panicle blast.

PMID- 24920971
TI  - Gene targeting using the Agrobacterium tumefaciens-mediated CRISPR-Cas system in
      rice.
AB  - BACKGROUND: The type II clustered, regularly interspaced, short palindromic
      repeat (CRISPR)/ CRISPR-associated protein 9 (Cas9) system is a novel molecular
      tool for site-specific genome modification. The CRISPR-Cas9 system was recently
      introduced into plants by transient or stable transformation. FINDINGS: Here, we
      report gene targeting in rice via the Agrobacterium tumefaciens-mediated CRISPR
      Cas9 system. Three 20-nt CRISPR RNAs were designed to pair with diverse sites
      followed by the protospacer adjacent motif (PAM) of the rice herbicide resistance
      gene BEL. After integrating the single-guide RNA (sgRNA) and Cas9 cassette in a
      single binary vector, transgenic rice plants harboring sgRNA:Cas9 were generated
      by A. tumefaciens-mediated stable transformation. By analyzing the targeting site
      on the genome of corresponding transgenic plants, the mutations were determined.
      The mutagenesis efficiency was varied from ~2% to ~16%. Furthermore, phenotypic
      analysis revealed that the biallelic mutated transgenic plant was sensitive to
      bentazon. CONCLUSIONS: Our results indicate that the agricultural trait could be
      purposely modified by sgRNA:Cas9-induced gene targeting. CRISPR-Cas9 system could
      be exploited as a powerful tool for trait improvements in crop breeding.

PMID- 24920969
TI  - International consensus on (ICON) anaphylaxis.
AB  - ICON: Anaphylaxis provides a unique perspective on the principal evidence-based
      anaphylaxis guidelines developed and published independently from 2010 through
      2014 by four allergy/immunology organizations. These guidelines concur with
      regard to the clinical features that indicate a likely diagnosis of anaphylaxis -
      a life-threatening generalized or systemic allergic or hypersensitivity
      reaction. They also concur about prompt initial treatment with intramuscular
      injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the
      patient supine (semi-reclining if dyspneic or vomiting), calling for help, and
      when indicated, providing supplemental oxygen, intravenous fluid resuscitation
      and cardiopulmonary resuscitation, along with concomitant monitoring of vital
      signs and oxygenation. Additionally, they concur that H1-antihistamines, H2
      antihistamines, and glucocorticoids are not initial medications of choice. For
      self-management of patients at risk of anaphylaxis in community settings, they
      recommend carrying epinephrine auto-injectors and personalized emergency action
      plans, as well as follow-up with a physician (ideally an allergy/immunology
      specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes
      unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules
      is available worldwide, other essentials, including supplemental oxygen,
      intravenous fluid resuscitation, and epinephrine auto-injectors are not
      universally available. ICON: Anaphylaxis proposes a comprehensive international
      research agenda that calls for additional prospective studies of anaphylaxis
      epidemiology, patient risk factors and co-factors, triggers, clinical criteria
      for diagnosis, randomized controlled trials of therapeutic interventions, and
      measures to prevent anaphylaxis recurrences. It also calls for facilitation of
      global collaborations in anaphylaxis research. IN ADDITION TO CONFIRMING THE
      ALIGNMENT OF MAJOR ANAPHYLAXIS GUIDELINES, ICON: Anaphylaxis adds value by
      including summary tables and citing 130 key references. It is published as an
      information resource about anaphylaxis for worldwide use by healthcare
      professionals, academics, policy-makers, patients, caregivers, and the public. 

PMID- 24920972
TI  - Heat-tolerant rice cultivars retain grain appearance quality under free-air CO2
      enrichment.
AB  - BACKGROUND: Heat-tolerant rice cultivars have been developed as a countermeasure
      to poor grain appearance quality under high temperatures. Recent studies showed
      that elevated CO2 concentrations (E-[CO2]) also reduce grain quality. To
      determine whether heat-tolerant cultivars also tolerate E-[CO2], we conducted a
      free-air CO2 enrichment (FACE) experiment with 12 rice cultivars differing in
      heat tolerance. RESULTS: The percentage of undamaged grains of five standard
      cultivars (Akitakomachi, Kinuhikari, Koshihikari, Matsuribare, Nipponbare)
      averaged 61.7% in the ambient [CO2] (AMB) plot and 51.7% in the FACE plot,
      whereas that of heat-tolerant cultivars (Eminokizuna, Wa2398, Kanto 257, Toyama
      80, Mineharuka, Kanto 259, Saikai 290) averaged 73.5% in AMB and 71.3% in FACE.
      This resulted in a significant [CO2] by cultivar interaction. The percentage of
      white-base or white-back grains increased from 8.4% in AMB to 17.1% in FACE in
      the sensitive cultivars, but from only 2.1% in AMB to only 4.4% in FACE in the
      heat-tolerant cultivars. CONCLUSION: Heat-tolerant cultivars retained their grain
      appearance quality at E-[CO2] under present air temperatures. Further
      improvements in appearance quality under present conditions will be needed to
      achieve improvements under E-[CO2], because E-[CO2] will likely lower the
      threshold temperature for heat stress.

PMID- 24920973
TI  - Genetic and physiological analysis of tolerance to acute iron toxicity in rice.
AB  - BACKGROUND: Fe toxicity occurs in lowland rice production due to excess ferrous
      iron (Fe(2+)) formation in reduced soils. To contribute to the breeding for
      tolerance to Fe toxicity in rice, we determined quantitative trait loci (QTL) by
      screening two different bi-parental mapping populations under iron pulse stresses
      (1,000 mg L(-1) = 17.9 mM Fe(2+) for 5 days) in hydroponic solution, followed by
      experiments with selected lines to determine whether QTLs were associated with
      iron exclusion (i.e. root based mechanisms), or iron inclusion (i.e. shoot-based
      mechanisms). RESULTS: In an IR29/Pokkali F8 recombinant inbred population, 7 QTLs
      were detected for leaf bronzing score on chromosome 1, 2, 4, 7 and 12,
      respectively, individually explaining 9.2-18.7% of the phenotypic variation. Two
      tolerant recombinant inbred lines carrying putative QTLs were selected for
      further experiments. Based on Fe uptake into the shoot, the dominant tolerance
      mechanism of the tolerant line FL510 was determined to be exclusion with its root
      architecture being conducive to air transport and thus the ability to oxidize
      Fe(2+) in rhizosphere. In line FL483, the iron tolerance was related mainly to
      shoot-based mechanisms (tolerant inclusion mechanism). In a
      Nipponbare/Kasalath/Nipponbare backcross inbred population, 3 QTLs were mapped on
      chromosomes 1, 3 and 8, respectively. These QTLs explained 11.6-18.6% of the
      total phenotypic variation. The effect of QTLs on chromosome 1 and 3 were
      confirmed by using chromosome segment substitution lines (SL), carrying Kasalath
      introgressions in the genetic background on Nipponbare. The Fe uptake in shoots
      of substitution lines suggests that the effect of the QTL on chromosome 1 was
      associated with shoot tolerance while the QTL on chromosome 3 was associated with
      iron exclusion. CONCLUSION: Tolerance of certain genotypes were classified into
      shoot- and root- based mechanisms. Comparing our findings with previously
      reported QTLs for iron toxicity tolerance, we identified co-localization for some
      QTLs in both pluse and chronic stresses, especially on chromosome 1.

PMID- 24920974
TI  - Dining at the health care buffet.

PMID- 24920975
TI  - One and the same.

PMID- 24920976
TI  - Barbed suture: a review of the technology and clinical uses in obstetrics and
      gynecology.
AB  - Surgical knots are simply a necessary evil needed to anchor smooth suture to
      allow it to function in its role in tissue reapproximation. Surgical knots reduce
      the tensile strength of all sutures by thinning and stretching the material. The
      tying of surgical knots introduces the potential of human error and interuser
      variability. Knot-secured smooth suture must create an uneven distribution of
      tension across the wound with the higher tension burdens placed at the knots.
      Given the excessive relative wound tension on the knot and the reasonable
      concerns of surgeons for suture failure due to knot slippage, there is a natural
      tendency toward overcoming these concerns by over-tightening knots; however,
      tighter knots may be worse for wound healing and strength than looser knots. In
      minimally invasive laparoscopic surgeries, the ability to quickly and properly
      tie surgical knots presents a new challenge. In cases in which knot tying is
      difficult, the use of knotless barbed suture can securely reapproximate tissues
      with less time, cost, and aggravation. This article reviews the technology behind
      barbed sutures with a focus on understanding how they differ from traditional
      smooth sutures and how barbed sutures have performed in in vitro and animal model
      testing, as well as in human clinical trials. 

PMID- 24920977
TI  - Screening for intimate partner violence during pregnancy.
AB  - Intimate partner violence (IPV) is defined as an actual or threatened abuse by an
      intimate partner that may be physical, sexual, psychological, or emotional in
      nature. Each year approximately 1.5 million women in the United States report
      some form of sexual or physical assault by an intimate partner; it is estimated
      that approximately 324,000 women are pregnant when violence occurs. Pregnancy may
      present a unique opportunity to identify and screen for patients experiencing
      IPV. This article provides health care practitioners and clinicians with the most
      current valid assessment and screening tools for evaluating pregnant women for
      IPV. 

PMID- 24920978
TI  - Modern Risk Assessment for Individualizing Treatment Concepts in Early-stage
      Breast Cancer.
AB  - Validated prognostic and predictive factors currently play an important role in
      treatment planning for patients with early-stage breast cancer. The role of
      personalized medicine has led to the search for markers that can be applied to
      individual patients to optimize treatment regimens. In addition to traditional
      clinicopathologic measures, scores and gene tests have been developed to
      independently predict risk of patients in the neoadjuvant and adjuvant settings.
      The discovery of these markers provides the opportunity to identify patients at
      such low risk of recurrence that toxic therapy side effects are not justified.
      Selection and management of patients with early-stage, hormone receptor-positive
      breast cancer who are appropriately treated with endocrine therapy alone after
      receiving locoregional therapy but do not necessarily require adjuvant
      chemotherapy is currently problematic. This article reviews the current state-of
      theart biomarker assessment methods and discusses the potential role for the
      prediction of chemotherapy benefit focusing on endocrine sensitive disease. 

PMID- 24920979
TI  - Use of thrombolytic agents to treat pulmonary embolism in pregnancy.
AB  - Pulmonary embolism in pregnancy is a major cause of maternal mortality and
      morbidity. We describe the case of a 27-year-old pregnant woman who underwent
      successful thrombolysis. Our patient presented to the emergency department after
      a fainting episode and complaining of shortness of breath. A computed tomography
      pulmonary angiogram revealed a pulmonary embolism, which was found to be causing
      significant right ventricular strain. After examination by our gynecologic and
      medical teams, she underwent successful thrombolysis, made a successful recovery,
      and carried an uneventful pregnancy. 

PMID- 24920980
TI  - Paradoxical increase in stroke mortality among Asian Indians in the United
      States.
AB  - OBJECTIVE: To better characterize the stroke mortality and risk factors among
      Asian Indians by using U.S. multiple-cause-of-death and National Health and
      Interview Survey data. METHODS: Age-adjusted fatal stroke incidence, stroke rate
      ratio with 95% confidence interval, and average annual percentage change (APC)
      over 10 years were calculated. RESULTS: The annual incidence of stroke mortality
      in 2000 was lowest among Asian Indians (88 per 100,000) followed by American
      Indians and Alaska Natives (112 per 100,000), whites (301 per 100,000) and
      African Americans (312 per 100,000). Significantly lower rates of hypertension
      and cigarette smoking in Asian Indians in 2000-2001 (compared with whites)
      explained the lower rates of stroke mortality. The APC increase over subsequent
      10 years was 13.5%, 0.9%, -2.5%, and -2.9% for Asian Indians, American Indians
      and Alaska Natives, whites, and African Americans, respectively. CONCLUSIONS:
      There is a paradoxical increase in stroke mortality among Asian Indians over the
      last 10 years in contrast to other population subsets.

PMID- 24920981
TI  - Endovascular treatment of basilar artery stenosis due to cerebral vasculopathy
      related to neurofibromatosis (NF1).
AB  - BACKGROUND: Cerebrovascular lesions are uncommon in neurofibromatosis type 1
      (NF1). CASE DESCRIPTION: We report a case of 34-year-old man with NF1 who
      developed posterior circulation stroke. Diffusion-weighted imaging showed acute
      infarcts in the right vertebra basilar artery territory. Digital subtraction
      angiography demonstrated significant stenosis of the basilar artery in the mid
      segment that was identified as the etiology of the symptoms. The vertebral
      arteries were tortuous and the basilar artery was ectatic. Subsequently endeavour
      resolute stent was placed across the lesion and post-procedure angiogram showed
      resolution of stenosis. CONCLUSION: Selective stenotic involvement of the basilar
      artery with ectatic vertebrobasilar circulation associated with NF1, which was
      successfully treated with endovascular method, was not been reported previously
      to our knowledge.

PMID- 24920982
TI  - Recurrent cerebral venous sinus thrombosis in a patient with increased factor
      VIII activity, increased lipoprotein (a) level and leukocytosis: a case report.
AB  - In this paper, we describe the case of recurrent cerebral venous sinus thrombosis
      in a patient with increased factor VIII activity, lipoprotein (a) level, and
      leukocytosis. In addition, we discuss the diagnosis of increased factor VIII
      activity in patients with cerebral venous thrombosis. With regard to therapy,
      studies need to be done to establish the duration of therapy with phenprocoumon
      and the possible use of new oral anticoagulant drugs (i.e., rivaroxaban and
      dabigatran) in first time and recurrent venous thrombosis. 

PMID- 24920983
TI  - Factors Associated with Increased Rates of Post-procedural Stroke or Death
      following Carotid Artery Stent Placement: A Systematic Review.
AB  - BACKGROUND AND PURPOSE: We provide an assessment of clinical, angiographic, and
      procedure related risk factors associated with stroke and/or death in patients
      undergoing carotid artery stent placement which will assist in patient
      stratification and identification of high-stent risk patients. METHODS: A
      comprehensive search of Medline from January 1st 1996 to December 31st 2011 was
      performed with key words "carotid artery stenosis", " carotid artery stenting",
      "carotid artery stent placement", "death" , " mortality", "stroke", "outcome",
      "clinical predictors", "angiographic predictors", was performed in various
      combinations. We independently abstracted data and assessed the quality of the
      studies. This analysis led to the selection of 71 articles for review. RESULTS:
      Clinical factors including age>=80 years, symptomatic status, procedure within 2
      weeks of symptoms, chronic renal failure, diabetes mellitus, and hemispheric TIA
      were associated with stroke (ischemic or hemorrhagic) and death within 1 month
      after carotid artery stent placement. Angiographic factors including left carotid
      artery intervention, stenosis > 90%, ulcerated and calcified plaques, lesion
      length > 10mm, thrombus at the site, ostial involvement, predilation without EPD,
      ICA-CCA angulation > 60%, aortic arch type III, and aortic arch calcification
      were also associated with 1 month stroke and/or death. Intra-procedural platelet
      GP IIb/IIIa inhibitors, protamine use, multiple stents, predilatation prior to
      stent placement were associated with stroke (ischemic or hemorrhagic) and death
      after carotid artery stent placement. Intraprocedural use of embolic protection
      devices and stent design (open versus closed cell design) did not demonstrate a
      consistent relationship with 1 month stroke and/or death. Procedural statin use,
      and operator and center experience of more than 50 procedures per year were
      protective for 1 month stroke and/or death. CONCLUSIONS: Our review identified
      risk factors for stroke, death, and MI within 1 month in patients undergoing
      carotid artery stent placement. Such information will result in better patient
      selection for carotid artery stent placement particularly in those who are also
      candidates for carotid endarterectomy.

PMID- 24920984
TI  - Is intravenous recombinant tissue plasminogen activator (r-tPA) safe in patients
      on Dabigatran?
AB  - INTRODUCTION: Dabigatran etexilate is a newly approved oral anticoagulant
      indicated for stroke prevention in nonvalvular atrial fibrillation. There are no
      reliable, rapidly available laboratory markers to assess its anticoagulant
      activity. There is no data on the safety of r-tPA on patients who are on
      dabigatran and it is not known whether r-tPA is safe in patients who are on
      dabigatran with a normal activated partial thromboplastin time (aPTT). CASE
      REPORT: We report the case of a 59-year-old male who is reported with right
      hemiparesis and global aphasia. Two days prior to admission he underwent elective
      cardioversion for atrial fibrillation. He had begun dabigatran at 150 mg BID 3
      days before cardioversion. Five days after commencing dabigatran, and 10 h after
      the last oral dose he presented with these symptoms. Patient fulfilled the
      criteria for r-tPA including a normal aPTT (30 s), normal prothrombin time (INR =
      1.0) and a normal creatinine clearance (glomerular filtration rate >60
      mL/min/1.73 m(2)). A brain CT without contrast was normal. After extensive
      discussion with the family, with clear understanding of the risks and benefits of
      such an approach in a patient who has been on dabigatran, consent was obtained,
      and r-tPA (0.9 mg/kg alteplase) was given. Patient's hospital course remained
      uncomplicated and he was discharged 4 days after the initial symptoms to an acute
      rehabilitation facility and is currently on coumadin with INR therapeutic goal
      between 2 and 3. CONCLUSION: More studies are needed to asses whether r-tPA might
      be safe in patients who are on dabigatran with a normal activated partial
      thromboplastin time and more than 10 h after the last dose.

PMID- 24920985
TI  - Vitamin D deficiency and osteoporosis in stroke survivors: an analysis of
      National Health and Nutritional Examination Survey (NHANES).
AB  - BACKGROUND AND PURPOSE: An inverse association between 25-hydroxyvitamin D
      (25[OH]D) levels and stroke was emphasized in recent studies. Our objective was
      to determine the rate of Vitamin D deficiency and risk of associated osteoporosis
      among stroke survivors in a nationally representative population. METHODS:
      Participants from the National Health and Nutritional Examination Survey (NHANES)
      from 2001 to 2006 were included. Stroke survivors were then divided into two
      groups depending on serum 25(OH)D levels: <30 ng/dl as Vitamin D deficiency and
      >=30 ng/dl as normal. Comparisons of demographics and risk factors between two
      groups were performed using SAS software. Multivariate analysis was performed to
      determine the association between Vitamin D deficiency and osteopororis in stroke
      survivors after adjusting for potential confounding factors. RESULTS: There were
      415 (4.0%) stroke survivors among 10,255 participants in NHANES. The mean age (+/
      SD) of stroke survivors was 67.6 (+/-17.3) years and 211 (50.8%) were men. Mean
      25(OH)D concentrations were not significantly different in patients with stroke
      (20.3 versus 21.8 ng/ml, p = 0.65) although the rate of osteoporosis was
      significantly higher among stroke survivors (17.9% versus 6.9%, p < 0.0001). Out
      of 415 stroke patients, Vitamin D deficiency was seen in 71.0% of patients. The
      rates of osteoporosis were similar between patients with or without Vitamin D
      deficiency. After adjusting for potential confounders, there was no association
      between Vitamin D deficiency and osteoporosis. CONCLUSIONS: Vitamin D deficiency
      and osteoporosis are highly prevalent among stroke survivors; however, there does
      not appear to be a relationship between the two entities.

PMID- 24920986
TI  - Instent restenosis after carotid stenting: treatment using an off-label cardiac
      scoring balloon.
AB  - BACKGROUND: Treatment of instent restenosis after carotid artery stenting because
      of circumferential or calcified lesions can be difficult and refractory to
      conventional balloon angioplasty. We describe the off-label use of a cardiac
      scoring balloon that was used for lesions refractory to angioplasty with other
      balloons. CASE DESCRIPTIONS: Two patients with a history of carotid artery
      stenting 6 and 8 years ago, presented with symptomatic carotid instent restenosis
      caused by circumferential and calcified lesions, respectively. Angioplasty with
      conventional compliant and noncompliant balloons was unsuccessful. An AngioSculpt
      percutaneous transluminal coronary angioplasty (PTCA) scoring balloon catheter
      (AngioScore, Fremont CA, USA) was successful in achieving vessel recanalization
      despite the refractory nature of these lesions. No further conventional balloons
      or use of cutting balloons was required. CONCLUSION: The AngioSculpt PTCA scoring
      balloon catheter can be a useful option for treatment of refractory calcified or
      circumferential carotid instent restenosis.

PMID- 24920987
TI  - Dural venous sinuses distortion and compression with supratentorial mass lesions:
      a mechanism for refractory intracranial hypertension?
AB  - OBJECTIVE: To determine the effect of supratentorial intraparenchymal mass
      lesions of various volumes on dural venous sinuses structure and transluminal
      pressures. METHODS: Three set of preparations were made using adult isolated head
      derived from fresh human cadaver. A supratentorial intraparenchymal balloon was
      introduced and inflated at various volumes and effect on dural venous sinuses was
      assessed by serial intravascular ultrasound, computed tomographic (CT), and
      magnetic resonance (MR) venograms. Contrast was injected through a catheter
      placed in sigmoid sinus for both CT and MR venograms. Serial trasluminal
      pressures were measured from middle part of superior sagittal sinus in another
      set of experiments. RESULTS: At intraparenchymal balloon inflation of 90 cm(3),
      there was attenuation of contrast enhancement of superior sagittal sinus with
      compression visualized in posterior part of the sinus without any evidence of
      compression in the remaining sinus. At intraparenchymal balloon inflation of 180
      and 210 cm(3), there was compression and obliteration of superior sagittal sinus
      throughout the length of the sinus. In the coronal sections, at intraparenchymal
      balloon inflations of 90 and 120 cm(3), compression and obliteration of the
      posterior part of superior sagittal sinus were visualized. In the axial images,
      basal veins were not visualized with intraparenchymal balloon inflation of 90
      cm(3) or greater although straight sinus was visualized at all levels of
      inflation. Trasluminal pressure in the middle part of superior sagittal sinus
      demonstrated a mild increase from 0 cm H(2)O to 0.4 cm H(2)O and 0.5 cm H(2)O
      with inflation of balloon to volume of 150 and 180 cm(3), respectively. There was
      a rapid increase in transluminal pressure from 6.8 cm H(2)O to 25.6 cm H(2)O as
      the supratentorial mass lesion increased from 180 to 200 cm(3). CONCLUSIONS: Our
      experiments identified distortion and segmental and global obliteration of dural
      venous sinuses secondary to supratentorial mass lesion and increase in
      transluminal pressure with large volume lesions. The secondary involvement of
      dural venous sinuses may represent a mechanism for refractory intracranial
      hypertension.

PMID- 24920988
TI  - Endoluminal stent reconstruction of low-grade, symptomatic carotid plaques: a
      treatment alternative-report of two cases.
AB  - INTRODUCTION: Medical treatment of low-grade (<50% luminal narrowing) symptomatic
      carotid stenosis has been the treatment of choice because trial data showed no
      evident benefit to carotid endarterectomy for these patients. Such patients may
      have recurrent neurological symptoms despite adequate medical therapy owing to
      recurrent plaque rupture. In such cases, carotid stenting may represent an option
      for treatment but has not been tested in trials because of previous failure of
      carotid endarterectomy to demonstrate any benefit for patients with low-grade
      carotid stenosis. The cases presented here illustrate the perioperative safety
      and potential benefit of carotid stenting for such patients with persistent
      neurological symptoms despite adequate medical therapy. CASE MATERIAL: Two
      patients with low-grade stenosis and recurrent transient ischemic attack or
      stroke despite antiplatelet therapy were treated with carotid stenting. Both
      patients were treated after recent ipsilateral neurological events in the absence
      of an evident cardioembolic source. Carotid plaque ulceration thought to be
      related to the ischemic events was present in both cases. No perioperative
      complications were noted. On followup, the patients showed resolution of symptoms
      and had no new neurological events. CONCLUSION: Carotid stenting of low-grade but
      symptomatic carotid plaque refractory to medical management represents a surgical
      option for treatment. Further studies may be warranted to evaluate stenting as a
      suitable treatment option.

PMID- 24920989
TI  - Visualization of a small hidden intracranial aneurysm during endovascular
      thrombectomy for acute MCA occlusion.
AB  - Spontaneous aneurysmal thrombosis as a cause for acute ischemic stroke is a
      rarely described complication of small unruptured intracranial aneurysms. We
      present an interesting case of a stroke in a woman with an occult acutely
      thrombosed middle cerebral artery bifurcation aneurysm that was found during
      successful thrombus aspiration of the occluded parent vessel. Although rare,
      small aneurysms have to be considered as a possible cause for a thrombotic vessel
      occlusion. Catheters and thrombectomy devices have to be used carefully while
      performing mechanical revascularization. 

PMID- 24920990
TI  - Brief Report: Concurrent cervical giant perimedullary arteriovenous fistula,
      aneurysm on a feeding artery of fistula and unilateral congenital carotid
      aplasia.
AB  - Giant perimedullary arteriovenous fistulae (GPAVFs) are extremely rare,
      particularly cervical GPAVFs whose incidence has not been tabulated. The
      occurrence of aneurysm on an artery feeding a GPAVF has previously not been
      described. Internal carotid artery aplasia is also very rare (0.01%). The
      concurrence of these disorders has previously not been recorded. We report a case
      of a 5-year-old female with increasing headaches, who was found to have
      intraventricular hemorrhage and above anomalies. Coil embolization of GPAVF and
      the adjacent aneurysm was attempted. Treatment was complicated by stroke and
      death. Embryological and anatomical factors underlying these anomalies as well
      as, management options are discussed. 

PMID- 24920992
TI  - Cocaine use and the likelihood of cardiovascular and all-cause mortality: data
      from the Third National Health and Nutrition Examination Survey Mortality Follow
      up Study.
AB  - BACKGROUND: Numerous case series have implicated cocaine use as a cause of both
      myocardial infarction (MI) and stroke on the basis of the temporal relationship
      between drug use and event onset. The relatively high prevalence of cocaine use
      in the US population, especially in younger individuals, mandates a more
      extensive investigation of this relationship. METHODS: We determined the
      relationship between cocaine use and cardiovascular and all-cause mortality in a
      nationally representative sample of 9013 US adults aged 18 to 45 years who
      participated in the Third National Health and Nutrition Examination Survey
      Mortality Follow-up Study using Cox proportional hazards analyses. We categorized
      the participants as nonusers if they responded to the lifetime cocaine use
      question as never used, as infrequent users if they responded as using <10 times,
      and as frequent or regular users if they reported using 10-99 times or >100
      times, respectively. Potential confounding factors in the association between
      cocaine use and death (cardiovascular and all cause) included age, sex,
      race/ethnicity, cigarette smoking, hypertension, diabetes mellitus,
      hyperlipidemia, educational attainment, body mass index, and insurance status. To
      estimate the impact of cocaine use on MI or stroke, we calculated the population
      attributable risk (PAR) percent for cocaine use with cardiovascular and all-cause
      mortality. We also estimated the years of life lost and total annual financial
      cost due to premature deaths in persons who reported regular use of cocaine.
      RESULTS: A total of 60 cardiovascular deaths and 384 all causes deaths were
      reported during a mean follow-up period of 14.7 +/- 2.6 years. After adjusting
      for differences in potential confounders, persons who reported regular lifetime
      cocaine use had a significantly higher likelihood of all-cause mortality
      (relative risk [RR], 1.9; 95% confidence interval [CI], 1.2-3.0 for >=100 times
      in lifetime) but not cardiovascular mortality (RR, 0.6; 95% CI, 0.1-4.7 for >=100
      times in lifetime). The PAR of regular cocaine use for all cause mortality among
      was 1.79%. The years of life lost due to regular cocaine use was 10.3 years for
      an adult aged 31 years. The overall yearly cost incurred due to premature deaths
      related to regular cocaine use was $1.1 billion. CONCLUSION: Regular cocaine use
      was associated with an increased risk of all cause mortality but this effect was
      not mediated through cardiovascular events. Behavior modification by public
      awareness and education may reduce the mortality and financial burden associated
      with cocaine use.

PMID- 24920993
TI  - Desolvation Costs of Salt Bridges across Protein Binding Interfaces: Similarities
      and Differences between Implicit and Explicit Solvent Models.
AB  - The prevalence of salt bridges across protein binding interfaces is surprising
      given the significant costs of desolvating the two charged groups upon binding.
      These desolvation costs, which are difficult to examine using laboratory
      experiments, have been computed in previous studies using the Poisson-Boltzmann
      (PB) implicit solvent model. Here, for the first time, we directly compare the PB
      implicit solvent model with several explicit water models in computing the
      desolvation penalties of salt bridges across protein-protein interfaces. We
      report both overall agreement as well as significant differences between the
      implicit and explicit solvent results. These differences highlight challenges to
      be faced in the application of implicit solvent methods.

PMID- 24920991
TI  - Endovascular treatment for acute ischemic stroke patients: implications and
      interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report
      from the Working Group of International Congress of Interventional Neurology.
AB  - OBJECTIVE: The results of Interventional Management of Stroke (IMS) III, Magnetic
      Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and
      SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular
      treatment for acute ischemic stroke. The purpose of this report is to review the
      components of the designs and methods of these trials and to describe the
      influence of those components on the interpretation of trial results. METHODS: A
      critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS
      EXPANSION is performed with emphasis on patient selection, shortcomings in
      procedural aspects, and methodology of data ascertainment and analysis. The
      influence of each component is estimated based on published literature including
      multicenter clinical trials reporting on endovascular treatment for acute
      ischemic stroke and myocardial infarction. RESULTS: We critically examined the
      time interval between symptom onset and treatment and rates of angiographic
      recanalization to differentiate between "endovascular treatment" and "parameter
      optimized endovascular treatment" as it relates to the IMS III, MR RESCUE, and
      SYNTHESIS EXPANSION trials. All the three trials failed to effectively test
      "parameter optimized endovascular treatment" due to the delay between symptom
      onset and treatment and less than optimal rates of recanalization. In all the
      three trials, the magnitude of benefit with endovascular treatment required to
      reject the null hypothesis was larger than could be expected based on previous
      studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of
      symptomatic intracerebral hemorrhages subsequent to treatment are similar between
      IV thrombolytics and endovascular treatment in matched acute ischemic stroke
      patients. The trials also indirectly validated the superiority/equivalence of IV
      thrombolytics (compared with endovascular treatment) in patients with minor
      neurological deficits and those without large vessel occlusion on computed
      tomographic/magnetic resonance angiography. CONCLUSIONS: The results do not
      support a large magnitude benefit of endovascular treatment in subjects
      randomized in all the three trials. The possibility that benefits of a smaller
      magnitude exist in certain patient populations cannot be excluded. Large
      magnitude benefits can be expected with implementation of "parameter optimized
      endovascular treatment" in patients with ischemic stroke who are candidates for
      IV thrombolytics.

PMID- 24920994
TI  - Anomalous Optoelectronic Properties of Chiral Carbon Nanorings...and One Ring to
      Rule Them All23.
AB  - Carbon nanorings are hoop-shaped, pi-conjugated macrocycles that form the
      fundamental annular segments of single-walled carbon nanotubes (SWNTs). In a very
      recent report, the structures of chiral carbon nanorings (which may serve as
      chemical templates for synthesizing chiral nanotubes) were experimentally
      synthesized and characterized for the first time. Here in our Letter we show that
      the excited-state properties of these unique chiral nanorings exhibit anomalous
      and extremely interesting optoelectronic properties with excitation energies
      growing larger as a function of size (in contradiction with typical quantum
      confinement effects). Although the first electronic excitation in armchair
      nanorings is forbidden with a weak oscillator strength, we find that the same
      excitation in chiral nanorings is allowed because of a strong geometric symmetry
      breaking. Most importantly, among all the possible nanorings synthesized in this
      fashion, we show that only one ring, corresponding to a SWNT with chiral indices
      (n+3,n+1), is extremely special with large photoinduced transitions that are most
      readily observable in spectroscopic experiments.

PMID- 24920995
TI  - Ether-Bond-Containing Ionic Liquids as Supercapacitor Electrolytes.
AB  - Electrochemical capacitors (ECs) are electrical energy storage devices that have
      the potential to be very useful in a wide range of applications, especially where
      there is a large disparity between peak and average power demands. The use of
      ionic liquids (ILs) as electrolytes in ECs can increase the energy density of
      devices; however, the viscosity and conductivity of ILs adversely influence the
      power density of the device. We present experimental results where several ILs
      containing different cations have been employed as the electrolyte in cells
      containing mesoporous carbon electrodes. Specifically, the behavior of ILs
      containing an ether bond in an alkyl side chain are compared with those of a
      similar structure and size but containing purely alkyl side chains. Using
      electrochemical impedance spectroscopy and constant current cycling, we show that
      the presence of the ether bond can dramatically increase the specific capacitance
      and reduce device resistance. These results have the important implication that
      such ILs can be used to tailor the physical properties and electrochemical
      performance of IL-based electrolytes.

PMID- 24920996
TI  - Quantum Effects in the Diffusion of Hydrogen on Ru(0001).
AB  - An understanding of hydrogen diffusion on metal surfaces is important not only
      for its role in heterogeneous catalysis and hydrogen fuel cell technology but
      also because it provides model systems where tunneling can be studied under well
      defined conditions. Here we report helium spin-echo measurements of the atomic
      scale motion of hydrogen on the Ru(0001) surface between 75 and 250 K. Quantum
      effects are evident at temperatures as high as 200 K, while below 120 K we
      observe a tunneling-dominated temperature-independent jump rate of 1.9 * 109 s-1,
      many orders of magnitude faster than previously seen. Quantum transition-state
      theory calculations based on ab initio path-integral simulations reproduce the
      temperature dependence of the rate at higher temperatures and predict a crossover
      to tunneling-dominated diffusion at low temperatures. However, the tunneling rate
      is underestimated, highlighting the need for future experimental and theoretical
      studies of hydrogen diffusion on this and other well-defined surfaces.

PMID- 24920997
TI  - Electron Diffraction of Superfluid Helium Droplets.
AB  - We present experimental results of electron diffraction of superfluid helium
      droplets and droplets doped with phthalocyanine gallium chloride and discuss the
      possibility of performing the same experiment with a laser aligned sample. The
      diffraction profile of pure droplets demonstrates dependence on the nozzle
      temperature, that is, on the average size of the droplets. Larger clusters
      demonstrate faster decay with increasing momentum transfer, whereas smaller
      clusters converge to isolated gas phase molecules at source temperatures of 18 K
      and higher. Electron diffraction of doped droplets shows similar modified
      molecular scattering intensity as that of the corresponding gas phase molecules.
      On the basis of fittings of the scattering profile, the number of remaining
      helium atoms of the doped droplets is estimated to be on the order of hundreds.
      This result offers guidance in assessing the possibility of electron diffraction
      from laser aligned molecules doped in superfluid helium droplets.

PMID- 24920998
TI  - Solvent-Induced Proton Hopping at a Water-Oxide Interface.
AB  - Despite widespread interest, a detailed understanding of the dynamics of proton
      transfer at interfaces is lacking. Here, we use ab initio molecular dynamics to
      unravel the connection between interfacial water structure and proton transfer
      for the widely studied and experimentally well-characterized water-ZnO(1010)
      interface. We find that upon going from a single layer of adsorbed water to a
      liquid multilayer, changes in the structure are accompanied by a dramatic
      increase in the proton-transfer rate at the surface. We show how hydrogen bonding
      and rather specific hydrogen-bond fluctuations at the interface are responsible
      for the change in the structure and proton-transfer dynamics. The implications of
      this for the chemical reactivity and for the modeling of complex wet oxide
      interfaces in general are also discussed.

PMID- 24920999
TI  - Deubiquitinating enzyme regulation of the p53 pathway: A lesson from Otub1.
AB  - Deubiquitination has emerged as an important mechanism of p53 regulation. A
      number of deubiquitinating enzymes (DUBs) from the ubiquitin-specific protease
      family have been shown to regulate the p53-MDM2-MDMX networks. We recently
      reported that Otub1, a DUB from the OTU-domain containing protease family, is a
      novel p53 regulator. Interestingly, Otub1 abrogates p53 ubiquitination and
      stabilizes and activates p53 in cells independently of its deubiquitinating
      enzyme activity. Instead, it does so by inhibiting the MDM2 cognate ubiquitin
      conjugating enzyme (E2) UbcH5. Otub1 also regulates other biological signaling
      through this non-canonical mechanism, suppression of E2, including the inhibition
      of DNA-damage-induced chromatin ubiquitination. Thus, Otub1 evolves as a unique
      DUB that mainly suppresses E2 to regulate substrates. Here we review the current
      progress made towards the understanding of the complex regulation of the p53
      tumor suppressor pathway by DUBs, the biological function of Otub1 including its
      positive regulation of p53, and the mechanistic insights into how Otub1
      suppresses E2. 

PMID- 24921000
TI  - Oxidation of KCNB1 K(+) channels in central nervous system and beyond.
AB  - KCNB1, a voltage-gated potassium (K(+)) channel that conducts a major delayed
      rectifier current in the brain, pancreas and cardiovascular system is a key
      player in apoptotic programs associated with oxidative stress. As a result, this
      protein represents a bona fide drug target for limiting the toxic effects of
      oxygen radicals. Until recently the consensus view was that reactive oxygen
      species trigger a pro-apoptotic surge in KCNB1 current via phosphorylation and
      SNARE-dependent incorporation of KCNB1 channels into the plasma membrane.
      However, new evidence shows that KCNB1 can be modified by oxidants and that
      oxidized KCNB1 channels can directly activate pro-apoptotic signaling pathways.
      Hence, a more articulated picture of the pro-apoptotic role of KCNB1 is emerging
      in which the protein induces cell's death through distinct molecular mechanisms
      and activation of multiple pathways. In this review article we discuss the
      diverse functional, toxic and protective roles that KCNB1 channels play in the
      major organs where they are expressed. 

PMID- 24921002
TI  - Review of application of mass spectrometry for analyses of anterior eye proteome.
AB  - Proteins have important functional roles in the body, which can be altered in
      disease states. The eye is a complex organ rich in proteins; in particular, the
      anterior eye is very sophisticated in function and is most commonly involved in
      ophthalmic diseases. Proteomics, the large scale study of proteins, has greatly
      impacted our knowledge and understanding of gene function in the post-genomic
      period. The most significant breakthrough in proteomics has been mass
      spectrometric identification of proteins, which extends analysis far beyond the
      mere display of proteins that classical techniques provide. Mass spectrometry
      functions as a "mass analyzer" which simplifies the identification and
      quantification of proteins extracted from biological tissue. Mass spectrometric
      analysis of the anterior eye proteome provides a differential display for protein
      comparison of normal and diseased tissue. In this article we present the key
      proteomic findings in the recent literature related to the cornea, aqueous humor,
      trabecular meshwork, iris, ciliary body and lens. Through this we identified
      unique proteins specific to diseases related to the anterior eye. 

PMID- 24921001
TI  - Regulation of cell survival and death during Flavivirus infections.
AB  - Flaviviruses, ss(+) RNA viruses, include many of mankind's most important
      pathogens. Their pathogenicity derives from their ability to infect many types of
      cells including neurons, to replicate, and eventually to kill the cells.
      Flaviviruses can activate tumor necrosis factor alpha and both intrinsic (Bax
      mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches
      for activating these pathways. Infection can lead to necrosis if viral load is
      extremely high or to other types of cell death if routes to apoptosis are
      blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In
      this case the autophagy temporarily spares the infected cell, allowing a longer
      period of reproduction for the virus, and the autophagy further protects the cell
      against other stresses such as those caused by reactive oxygen species. Several
      of the viral proteins have been shown to induce apoptosis or autophagy on their
      own, independent of the presence of other viral proteins. Given the versatility
      of these viruses to adapt to and manipulate the metabolism, and thus to control
      the survival of, the infected cells, we need to understand much better how the
      specific viral proteins affect the pathways to apoptosis and autophagy. Only in
      this manner will we be able to minimize the pathology that they cause. 

PMID- 24921003
TI  - Role of PRMTs in cancer: Could minor isoforms be leaving a mark?
AB  - Protein arginine methyltransferases (PRMTs) catalyze the methylation of a variety
      of protein substrates, many of which have been linked to the development,
      progression and aggressiveness of different types of cancer. Moreover, aberrant
      expression of PRMTs has been observed in several cancer types. While the link
      between PRMTs and cancer is a relatively new area of interest, the functional
      implications documented thus far warrant further investigations into its
      therapeutic potential. However, the expression of these enzymes and the
      regulation of their activity in cancer are still significantly understudied.
      Currently there are nine main members of the PRMT family. Further, the existence
      of alternatively spliced isoforms for several of these family members provides an
      additional layer of complexity. Specifically, PRMT1, PRMT2, CARM1 and PRMT7 have
      been shown to have alternative isoforms and others may be currently unrealized.
      Our knowledge with respect to the relative expression and the specific functions
      of these isoforms is largely lacking and needs attention. Here we present a
      review of the current knowledge of the known alternative PRMT isoforms and
      provide a rationale for how they may impact on cancer and represent potentially
      useful targets for the development of novel therapeutic strategies. 

PMID- 24921004
TI  - What have we learned about the kallikrein-kinin and renin-angiotensin systems in
      neurological disorders?
AB  - The kallikrein-kinin system (KKS) is an intricate endogenous pathway involved in
      several physiological and pathological cascades in the brain. Due to the
      pathological effects of kinins in blood vessels and tissues, their formation and
      degradation are tightly controlled. Their components have been related to several
      central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's
      disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors
      (B1R and B2R) may have a role in the pathophysiology of certain central nervous
      system diseases. It has been suggested that kinin B1R is up-regulated in
      pathological conditions and has a neurodegenerative pattern, while kinin B2R is
      constitutive and can act as a neuroprotective factor in many neurological
      conditions. The renin angiotensin system (RAS) is an important blood pressure
      regulator and controls both sodium and water intake. AngII is a potent
      vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme
      responsible for its release. AngII acts mainly on the AT1 receptor, with
      involvement in several systemic and neurological disorders. Brain RAS has been
      associated with physiological pathways, but is also associated with brain
      disorders. This review describes topics relating to the involvement of both
      systems in several forms of brain dysfunction and indicates components of the KKS
      and RAS that have been used as targets in several pharmacological approaches. 

PMID- 24921005
TI  - "Stop Ne(c)king around": How interactomics contributes to functionally
      characterize Nek family kinases.
AB  - Aside from Polo and Aurora, a third but less studied kinase family involved in
      mitosis regulation is the never in mitosis-gene A (NIMA)-related kinases (Neks).
      The founding member of this family is the sole member NIMA of Aspergillus
      nidulans, which is crucial for the initiation of mitosis in that organism. All 11
      human Neks have been functionally assigned to one of the three core functions
      established for this family in mammals: (1) centrioles/mitosis; (2) primary
      ciliary function/ciliopathies; and (3) DNA damage response (DDR). Recent
      findings, especially on Nek 1 and 8, showed however, that several Neks
      participate in parallel in at least two of these contexts: primary ciliary
      function and DDR. In the core section of this in-depth review, we report the
      current detailed functional knowledge on each of the 11 Neks. In the discussion,
      we return to the cross-connections among Neks and point out how our and other
      groups' functional and interactomics studies revealed that most Neks interact
      with protein partners associated with two if not all three of the functional
      contexts. We then raise the hypothesis that Neks may be the connecting regulatory
      elements that allow the cell to fine tune and synchronize the cellular events
      associated with these three core functions. The new and exciting findings on the
      Nek family open new perspectives and should allow the Neks to finally claim the
      attention they deserve in the field of kinases and cell cycle biology. 

PMID- 24921006
TI  - Value of a newly sequenced bacterial genome.
AB  - Next-generation sequencing (NGS) technologies have made high-throughput
      sequencing available to medium- and small-size laboratories, culminating in a
      tidal wave of genomic information. The quantity of sequenced bacterial genomes
      has not only brought excitement to the field of genomics but also heightened
      expectations that NGS would boost antibacterial discovery and vaccine
      development. Although many possible drug and vaccine targets have been
      discovered, the success rate of genome-based analysis has remained below
      expectations. Furthermore, NGS has had consequences for genome quality, resulting
      in an exponential increase in draft (partial data) genome deposits in public
      databases. If no further interests are expressed for a particular bacterial
      genome, it is more likely that the sequencing of its genome will be limited to a
      draft stage, and the painstaking tasks of completing the sequencing of its genome
      and annotation will not be undertaken. It is important to know what is lost when
      we settle for a draft genome and to determine the "scientific value" of a newly
      sequenced genome. This review addresses the expected impact of newly sequenced
      genomes on antibacterial discovery and vaccinology. Also, it discusses the
      factors that could be leading to the increase in the number of draft deposits and
      the consequent loss of relevant biological information. 

PMID- 24921007
TI  - Activated protein C: A regulator of human skin epidermal keratinocyte function.
AB  - Activated protein C (APC) is a physiological anticoagulant, derived from its
      precursor protein C (PC). Independent of its anticoagulation, APC possesses
      strong anti-inflammatory, anti-apoptotic and barrier protective properties which
      appear to be protective in a number of disorders including chronic wound healing.
      The epidermis is the outermost skin layer and provides the first line of defence
      against the external environment. Keratinocytes are the most predominant cells in
      the epidermis and play a critical role in maintaining epidermal barrier function.
      PC/APC and its receptor, endothelial protein C receptor (EPCR), once thought to
      be restricted to the endothelium, are abundantly expressed by skin epidermal
      keratinocytes. These cells respond to APC by upregulating proliferation,
      migration and matrix metalloproteinase-2 activity and inhibiting
      apoptosis/inflammation leading to a wound healing phenotype. APC also increases
      barrier function of keratinocyte monolayers by promoting the expression of tight
      junction proteins and re-distributing them to cell-cell contacts. These
      cytoprotective properties of APC are mediated through EPCR, protease-activated
      receptors, epidermal growth factor receptor or Tie2. Future preventive and
      therapeutic uses of APC in skin disorders associated with disruption of barrier
      function and inflammation look promising. This review will focus on APC's
      function in skin epidermis/keratinocytes and its therapeutical potential in skin
      inflammatory conditions. 

PMID- 24921010
TI  - FBW7-mediated ubiquitination and degradation of KLF5.
AB  - Kruppel-like factor (KLF) family proteins are transcription factors that regulate
      numerous cellular functions, such as cell proliferation, differentiation, and
      cell death. Posttranslational modification of KLF proteins is important for their
      transcriptional activities and biological functions. One KLF family member with
      important roles in cell proliferation and tumorigenesis is KLF5. The function of
      KLF5 is tightly controlled by post-translational modifications, including
      SUMOylation, phosphorylation, and ubiquitination. Recent studies from our lab and
      others' have demonstrated that the tumor suppressor FBW7 is an essential E3
      ubiquitin ligase that targets KLF5 for ubiquitination and degradation. KLF5
      contains functional Cdc4 phospho-degrons (CPDs), which are required for its
      interaction with FBW7. Mutation of CPDs in KLF5 blocks the ubiquitination and
      degradation of KLF5 by FBW7. The protein kinase Glycogen synthase kinase 3beta is
      involved in the phosphorylation of KLF5 CPDs. In both cancer cell lines and mouse
      models, it has been shown that FBW7 regulates the expression of KLF5 target genes
      through the modulation of KLF5 stability. In this review, we summarize the
      current progress on delineating FBW7-mediated KLF5 ubiquitination and
      degradation. 

PMID- 24921009
TI  - Ceruloplasmin-ferroportin system of iron traffic in vertebrates.
AB  - Safe trafficking of iron across the cell membrane is a delicate process that
      requires specific protein carriers. While many proteins involved in iron uptake
      by cells are known, only one cellular iron export protein has been identified in
      mammals: ferroportin (SLC40A1). Ceruloplasmin is a multicopper enzyme endowed
      with ferroxidase activity that is found as a soluble isoform in plasma or as a
      membrane-associated isoform in specific cell types. According to the currently
      accepted view, ferrous iron transported out of the cell by ferroportin would be
      safely oxidized by ceruloplasmin to facilitate loading on transferrin. Therefore,
      the ceruloplasmin-ferroportin system represents the main pathway for cellular
      iron egress and it is responsible for physiological regulation of cellular iron
      levels. The most recent findings regarding the structural and functional features
      of ceruloplasmin and ferroportin and their relationship will be described in this
      review. 

PMID- 24921011
TI  - Extracellular O-linked beta-N-acetylglucosamine: Its biology and relationship to
      human disease.
AB  - The O-linked beta-N-acetylglucosamine (O-GlcNAc)ylation of cytoplasmic and
      nuclear proteins regulates basic cellular functions and is involved in the
      etiology of neurodegeneration and diabetes. Intracellular O-GlcNAcylation is
      catalyzed by a single O-GlcNAc transferase, O-GlcNAc transferase (OGT). Recently,
      an atypical O-GlcNAc transferase, extracellular O-linked beta-N-acetylglucosamine
      (EOGT), which is responsible for the modification of extracellular O-GlcNAc, was
      identified. Although both OGT and EOGT are regulated through the common
      hexosamine biosynthesis pathway, EOGT localizes to the lumen of the endoplasmic
      reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT
      independent manner. In Drosophila, loss of Eogt gives phenotypes similar to those
      caused by defects in the apical extracellular matrix. Dumpy, a membrane-anchored
      apical extracellular matrix protein, was identified as a major O-GlcNAcylated
      protein, and EOGT mediates Dumpy-dependent cell adhesion. In mammals,
      extracellular O-GlcNAc was detected on extracellular proteins including heparan
      sulfate proteoglycan 2, Nell1, laminin subunit alpha-5, Pamr1, and transmembrane
      proteins, including Notch receptors. Although the physiological function of O
      GlcNAc in mammals has not yet been elucidated, exome sequencing identified
      homozygous EOGT mutations in patients with Adams-Oliver syndrome, a rare
      congenital disorder characterized by aplasia cutis congenita and terminal
      transverse limb defects. This review summarizes the current knowledge of
      extracellular O-GlcNAc and its implications in the pathological processes in
      Adams-Oliver syndrome. 

PMID- 24921008
TI  - Endoglin in liver fibrogenesis: Bridging basic science and clinical practice.
AB  - Endoglin, also known as cluster of differentiation CD105, was originally
      identified 25 years ago as a novel marker of endothelial cells. Later it was
      shown that endoglin is also expressed in pro-fibrogenic cells including mesangial
      cells, cardiac and scleroderma fibroblasts, and hepatic stellate cells. It is an
      integral membrane-bound disulfide-linked 180 kDa homodimeric receptor that acts
      as a transforming growth factor-beta (TGF-beta) auxiliary co-receptor. In humans,
      several hundreds of mutations of the endoglin gene are known that give rise to an
      autosomal dominant bleeding disorder that is characterized by localized
      angiodysplasia and arteriovenous malformation. This disease is termed hereditary
      hemorrhagic telangiectasia type I and induces various vascular lesions, mainly on
      the face, lips, hands and gastrointestinal mucosa. Two variants of endoglin
      (i.e., S- and L-endoglin) are formed by alternative splicing that distinguishes
      from each other in the length of their cytoplasmic tails. Moreover, a soluble
      form of endoglin, i.e., sol-Eng, is shedded by the matrix metalloprotease-14 that
      cleaves within the extracellular juxtamembrane region. Endoglin interacts with
      the TGF-beta signaling receptors and influences Smad-dependent and -independent
      effects. Recent work has demonstrated that endoglin is a crucial mediator during
      liver fibrogenesis that critically controls the activity of the different Smad
      branches. In the present review, we summarize the present knowledge of endoglin
      expression and function, its involvement in fibrogenic Smad signaling, current
      models to investigate endoglin function, and the diagnostic value of endoglin in
      liver disease. 

PMID- 24921012
TI  - Regulation and function of signal transducer and activator of transcription 3.
AB  - Signal transducer and activator of transcription 3 (STAT3), a member of the STAT
      family, is a key regulator of many physiological and pathological processes.
      Significant progress has been made in understanding the transcriptional control,
      posttranslational modification, cellular localization and functional regulation
      of STAT3. STAT3 can translocate into the nucleus and bind to specific promoter
      sequences, thereby exerting transcriptional regulation. Recent studies have shown
      that STAT3 can also translocate into mitochondria, participating in aerobic
      respiration and apoptosis. In addition, STAT3 plays an important role in
      inflammation and tumorigenesis by regulating cell proliferation, differentiation
      and metabolism. Conditional knockout mouse models make it possible to study the
      physiological function of STAT3 in specific tissues and organs. This review
      summarizes the latest advances in the understanding of the expression, regulation
      and function of STAT3 in physiological and tumorigenic processes. 

PMID- 24921013
TI  - Functional analysis of human Na(+)/K(+)-ATPase familial or sporadic hemiplegic
      migraine mutations expressed in Xenopus oocytes.
AB  - AIM: Functional characterization of ATP1A2 mutations that are related to familial
      or sporadic hemiplegic migraine (FHM2, SHM). METHODS: cRNA of human Na(+)/K(+)
      ATPase alpha2- and beta1-subunits were injected in Xenopus laevis oocytes. FHM2
      or SHM mutations of residues located in putative alpha/beta interaction sites or
      in the alpha2-subunit's C-terminal region were investigated. Mutants were
      analyzed by the two-electrode voltage-clamp (TEVC) technique on Xenopus oocytes.
      Stationary K(+)-induced Na(+)/K(+) pump currents were measured, and the voltage
      dependence of apparent K(+) affinity was investigated. Transient currents were
      recorded as ouabain-sensitive currents in Na(+) buffers to analyze kinetics and
      voltage-dependent pre-steady state charge translocations. The expression of
      constructs was verified by preparation of plasma membrane and total membrane
      fractions of cRNA-injected oocytes. RESULTS: Compared to the wild-type enzyme,
      the mutants G900R and E902K showed no significant differences in the voltage
      dependence of K(+)-induced currents, and analysis of the transient currents
      indicated that the extracellular Na(+) affinity was not affected. Mutant G855R
      showed no pump activity detectable by TEVC. Also for L994del and Y1009X, pump
      currents could not be recorded. Analysis of the plasma and total membrane
      fractions showed that the expressed proteins were not or only minimally targeted
      to the plasma membrane. Whereas the mutation K1003E had no impact on K(+)
      interaction, D999H affected the voltage dependence of K(+)-induced currents.
      Furthermore, kinetics of the transient currents was altered compared to the wild
      type enzyme, and the apparent affinity for extracellular Na(+) was reduced.
      CONCLUSION: The investigated FHM2/SHM mutations influence protein function
      differently depending on the structural impact of the mutated residue.

PMID- 24921014
TI  - Binding of rhodopsin and rhodopsin analogues to transducin, rhodopsin kinase and
      arrestin-1.
AB  - AIM: To investigate the interaction of reconstituted rhodopsin, 9-cis-retinal
      rhodopsin and 13-cis-retinal-rhodopsin with transducin, rhodopsin kinase and
      arrestin-1. METHODS: Rod outer segments (ROS) were isolated from bovine retinas.
      Following bleaching of ROS membranes with hydroxylamine, rhodopsin and rhodopsin
      analogues were generated with the different retinal isomers and the concentration
      of the reconstituted pigments was calculated from their UV/visible absorption
      spectra. Transducin and arrestin-1 were purified to homogeneity by column
      chromatography, and an enriched-fraction of rhodopsin kinase was obtained by
      extracting freshly prepared ROS in the dark. The guanine nucleotide binding
      activity of transducin was determined by Millipore filtration using beta,gamma
      imido-((3)H)-guanosine 5'-triphosphate. Recognition of the reconstituted pigments
      by rhodopsin kinase was determined by autoradiography following incubation of ROS
      membranes containing the various regenerated pigments with partially purified
      rhodopsin kinase in the presence of (gamma-(32)P) ATP. Binding of arrestin-1 to
      the various pigments in ROS membranes was determined by a sedimentation assay
      analyzed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS:
      Reconstituted rhodopsin and rhodopsin analogues containing 9-cis-retinal and 13
      cis-retinal rendered an absorption spectrum showing a maximum peak at 498 nm, 486
      nm and about 467 nm, respectively, in the dark; which was shifted to 380 nm, 404
      nm and about 425 nm, respectively, after illumination. The percentage of
      reconstitution of rhodopsin and the rhodopsin analogues containing 9-cis-retinal
      and 13-cis-retinal was estimated to be 88%, 81% and 24%, respectively. Although
      only residual activation of transducin was observed in the dark when
      reconstituted rhodopsin and 9-cis-retinal-rhodopsin was used, the rhodopsin
      analogue containing the 13-cis isomer of retinal was capable of activating
      transducin independently of light. Moreover, only a basal amount of the
      reconstituted rhodopsin and 9-cis-retinal-rhodopsin was phosphorylated by
      rhodopsin kinase in the dark, whereas the pigment containing the 13-cis-retinal
      was highly phosphorylated by rhodopsin kinase even in the dark. In addition,
      arrestin-1 was incubated with rhodopsin, 9-cis-retinal-rhodopsin or 13-cis
      retinal-rhodopsin. Experiments were performed using both phosphorylated and non
      phosphorylated regenerated pigments. Basal amounts of arrestin-1 interacted with
      rhodopsin, 9-cis-retinal-rhodopsin and 13-cis-retinal-rhodopsin under dark and
      light conditions. Residual arrestin-1 was also recognized by the phosphorylated
      rhodopsin and phosphorylated 9-cis-retinal-rhodopsin in the dark. However,
      arrestin-1 was recognized by phosphorylated 13-cis-retinal-rhodopsin in the dark.
      As expected, all reformed pigments were capable of activating transducin and
      being phosphorylated by rhodopsin kinase in a light-dependent manner.
      Additionally, all reconstituted photolyzed and phosphorylated pigments were
      capable of interacting with arrestin-1. CONCLUSION: In the dark, the rhodopsin
      analogue containing the 13-cis isomer of retinal appears to fold in a pseudo
      active conformation that mimics the active photointermediate of rhodopsin.

PMID- 24921015
TI  - The status and future challenges of tobacco control policy in Korea.
AB  - Tobacco use is the most important preventable risk factor for premature death.
      The World Health Organization (WHO) Framework Convention on Tobacco Control
      (FCTC), the first international public health treaty, came into force in 2005.
      This paper reviews the present status of tobacco control policies in Korea
      according to the WHO FCTC recommendations. In Korea, cigarette use is high among
      adult males (48.2% in 2010), and cigarette prices are the lowest among the
      Organization for Economic Cooperation and Development countries with no tax
      increases since 2004. Smoke-free policies have shown incremental progress since
      1995, but smoking is still permitted in many indoor public places. More than 30%
      of non-smoking adults and adolescents are exposed to second-hand smoke. Public
      education on the harmful effects of tobacco is currently insufficient and the
      current policies have not been adequately evaluated. There is no comprehensive
      ban on tobacco advertising, promotion, or sponsorship in Korea. Cigarette
      packages have text health warnings on only 30% of the main packaging area, and
      misleading terms such as "mild" and "light" are permitted. There are nationwide
      smoking cessation clinics and a Quitline service, but cessation services are not
      covered by public insurance schemes and there are no national treatment
      guidelines. The sale of tobacco to minors is prohibited by law, but is poorly
      enforced. The socioeconomic inequality of smoking prevalence has widened,
      although the government considers inequality reduction to be a national goal. The
      tobacco control policies in Korea have faltered recently and priority should be
      given to the development of comprehensive tobacco control policies. 

PMID- 24921016
TI  - Burden of disease in Japan: using national and subnational data to inform local
      health policy.
AB  - The Global Burden of Disease (GBD) study has been instrumental in guiding global
      health policy development since the early 1990s. The GBD 2010 project provided
      rich information about the key causes of mortality, disability-adjusted life
      years, and their associated risk factors in Japan and provided a unique
      opportunity to incorporate these data into health planning. As part of the latest
      update of this project, GBD 2013, the Japanese GBD collaborators plan to update
      and refine the available burden of disease data by incorporating sub-national
      estimates of the burden of disease at the prefectural level. These estimates will
      provide health planners and policy makers at both the national and prefectural
      level with new, more refined tools to adapt local public health initiatives to
      meet the health needs of local populations. Moreover, they will enable the
      Japanese health system to better respond to the unique challenges in their
      rapidly aging population and as a complex combination of non-communicable disease
      risk factors begin to dominate the policy agenda. Regional collaborations will
      enable nations to learn from the experiences of other nations that may be at
      different stages of the epidemiological transition and have different exposure
      profiles and associated health effects. Such analyses and improvements in the
      data collection systems will further improve the health of the Japanese, maintain
      Japan's excellent record of health equity, and provide a better understanding of
      the direction of health policy in the region. 

PMID- 24921017
TI  - Airborne nicotine concentrations in the workplaces of tobacco farmers.
AB  - OBJECTIVES: Nicotine is a natural alkaloid and insecticide in tobacco leaves.
      Green tobacco sickness (GTS) is known as a disease of acute nicotine intoxication
      among tobacco farmers. Until now, GTS has been recognized globally as a disease
      that results from nicotine absorption through the skin. However, we assumed that
      GTS might also result from nicotine inhalation as well as absorption. We aimed to
      measure the airborne nicotine concentrations in various work environments of
      Korean tobacco farmers. METHODS: We measured the nicotine concentrations in the
      tobacco fields, private curing barns, and joint curing barns of farmers from July
      to October 2010. All sampling and analyses of airborne nicotine were conducted
      according to the National Institute for Occupational Safety and Health manual of
      analytic methods. RESULTS: The airborne nicotine concentrations (geometric mean
      [geometric standard deviation]) in the tobacco field were 83.4 mg/m(3) (1.2) in
      the upper region and 93.3 mg/m(3) (1.2) in the lower region. In addition, the
      nicotine concentration by personal sampling was 150.1 mg/m(3). Similarly, the
      nicotine concentrations in the private curing barn, workers in curing barns, the
      front yard of the curing barn, and in the joint curing barn were 323.7 mg/m(3)
      (2.0), 121.0 mg/m(3) (1.5), 73.7 mg/m(3) (1.7), and 610.3 mg/m(3) (1.0),
      respectively. CONCLUSIONS: The nicotine concentration in the workplaces of
      tobacco farmers was very high. Future studies should measure the environmental
      concentration of nicotine that is inhaled by tobacco farmers.

PMID- 24921018
TI  - The effect of sleep duration on the risk of unintentional injury in Korean
      adults.
AB  - OBJECTIVES: The decrease or increase in sleep duration has recently been
      recognized as a risk factor for several diseases, including hypertension and
      obesity. Many studies have explored the relationship of decreased sleep durations
      and injuries, but few have examined the relationship between increased sleep
      duration and injury. The objective of this research is to identify the risk for
      injury associated with both decreased and increased sleep durations. METHODS:
      Data from the 2010 Community Health Survey were used in this study. We conducted
      logistic regression with average sleep duration as the independent variable,
      injury as a dependent variable, and controlling for age, sex, occupation,
      education, region (cities and provinces), smoking, alcohol use, body mass index,
      hypertension, diabetes, arthritis, and depression. Seven categories of sleep
      duration were established: <=4, 5, 6, 7, 8, 9, and >=10 hours. RESULTS: Using 7
      hours of sleep as the reference, the adjusted injury risk (odds ratio) for those
      sleeping a total of <=4 h/d was 1.53; 1.28 for 5 hours, for 1.11 for 6 hours,
      0.98 for 8 hours, 1.12 for 9 hours, and 1.48 for >=10 hours. The difference in
      risk was statistically significant for each category except for the 8 and 9
      hours. In this study, risk increased as the sleep duration decreased or
      increased, except for the 8 and 9 hours. CONCLUSIONS: This research found that
      either a decrease or increase in sleep duration was associated with an increased
      risk for injury. The concept of proper sleep duration can be evaluated by its
      associated injury risk.

PMID- 24921019
TI  - Variation in meal-skipping rates of Korean adolescents according to socio
      economic status: results of the Korea Youth Risk Behavior Web-based Survey.
AB  - OBJECTIVES: To identify and evaluate the trend of meal-skipping rates among
      Korean adolescents with their contributing causes and the influence of household
      income level on meal skipping. METHODS: Using 2008, 2010, and 2012 data from the
      Korea Youth Risk Behavior Web-based Survey of 222 662 students, a cross-sectional
      study with subgroup analysis was performed. We calculated odds ratios for
      skipping each meal 5 or more times in a week by household socio-economic status
      using a multiple logistic regression model. The secular change in the meal
      skipping rates by the students' family affluence scale was analyzed by comparing
      the meal-skipping students within each subgroup and odds ratios for the same
      event over time. RESULTS: Through 2008 to 2012, most of the meal-skipping rates
      generally showed a continuous increase or were almost unchanged in both sexes,
      except for breakfast skipping in several subgroups. Students in low-income
      households not living with both parents had the highest meal-skipping rates and
      odds ratios for frequent meal skipping. In a time-series subgroup analysis, the
      overall odds ratios for the same event increased during 2008 to 2012, with a
      slight reduction in the gap between low and higher income levels with regard to
      meal skipping during 2010 to 2012. CONCLUSIONS: Household socio-economic status
      and several other factors had a significant influence on Korean adolescent meal
      skipping rates. Although the gap in eating behavior associated with household
      socio-economic differences is currently decreasing, further study and appropriate
      interventions are needed.

PMID- 24921020
TI  - Assessment of occupational symptoms and chemical exposures for nail salon
      technicians in Daegu City, Korea.
AB  - OBJECTIVES: This study aimed to evaluate occupational symptoms and chemical
      exposures of nail salon technicians. METHODS: Work-related symptoms of nail salon
      technicians in Daegu City were surveyed using a researcher-administered
      questionnaire, and responses were compared to those of non-exposed office workers
      as controls. Personal exposure level of airborne volatile organic compounds was
      also monitored using passive samplers. RESULTS: A total of 159 subjects in 120
      salons were interviewed. Average work-shift concentrations of 13 chemicals were
      measured for 50 workers from 30 salons using personal passive samplers. The most
      frequently reported respiratory or neurologic symptoms by nail shop technicians
      compared to controls were nose irritation (odds ratio [OR], 54.0; confidence
      interval [CI], 21.6 to 134.8), followed by headache (OR, 9.3; CI, 4.7 to 18), and
      throat irritation (OR, 4.3; CI, 2.2 to 8.5). For eyes and skin, 92% of
      respondents complained eye irritation (OR, 13.1; CI, 5.7 to 30.1). In
      musculoskeletal symptoms, workers reported pain or discomfort in shoulders (OR,
      20.3; CI, 7.7 to 54) and neck (OR, 19.7; CI, 8.9 to 43.6). From personal
      measurements, the proportion of exceeding the Korean Occupational Exposure Limit
      was the highest for acetone with 64%, followed by toluene (50%), butyl acetate
      (46%), and methyl methacrylate (12%). However, the service was being provided
      without a proper ventilation system in most surveyed shops. CONCLUSIONS: Based on
      these findings, it is warranted to have appropriate local exhaust ventilation
      place to ensure adequate health protection of nail shop technicians as well as
      customers. At the same time, greater policy interests are warranted in nail care
      business to protect health of both workers and customers.

PMID- 24921021
TI  - Epidemiological investigation of an outbreak of salmonellosis in Gyeongju, Korea.
AB  - OBJECTIVES: A salmonellosis outbreak occurred within a community of Gyeongju
      residents who ingested catered food from a wedding in June 2009. We aimed to
      epidemiologically investigate the probable vehicle of the infection. METHODS: We
      conducted a retrospective cohort study on 34 local residents who ingested the
      wedding food. RESULTS: Among the 34 residents, 31 (91.2%) reported symptoms of
      infection after eating the food. Among all of the wedding foods, pan-fried foods
      were highly associated with the diarrheal attack rate. On bacteriological
      examination, Salmonella species were detected in the pan-fried foods among the
      leftover foods and in 17 of the 31 stool specimens from the cases. There were
      five different types of pan-fried foods, but the onset of symptoms was
      independent of the ingredients used. We found that the pan-fried food was
      prepared at a food store in Seoul and that eggs were a common ingredient.
      CONCLUSIONS: The major cause of the salmonellosis in this population was presumed
      to be the pan-fried food prepared with contaminated eggs. These food items might
      have been partially undercooked because of their irregular shape, which allowed
      the Salmonella species to survive and multiply before ingestion.

PMID- 24921022
TI  - Comparative Study between Intravenous and Intraperitoneal Stem Cell Therapy in
      Amiodarone Induced Lung Injury in Rat.
AB  - BACKGROUND AND OBJECTIVES: The fibrosing form of lung injury (occupational,
      environmental, infective or drug induced) is associated with significant
      morbidity and mortality. Amiodarone (AM), often prescribed for control of
      arrhythmias is considered a potential cause. No effective treatment was
      confirmed, except lung transplantation. Intravenous (IV) stem cell therapy may
      produce pulmonary emboli or infarctions. Despite being commonly used in clinical
      practice, the intraperitoneal (IP.) route has been rarely used for cell delivery.
      The present study aimed at investigating and comparing the possible effect of IP
      stem cell therapy (SCT) on pulmonary toxicity versus the intravenous route in a
      rat model of amiodarone induced lung damage. METHODS AND RESULTS: 36 adult male
      albino rats were divided into 4 groups. Rats of AM group were given 30 mg/kg
      daily orally for 4 weeks. Rats of IV SCT group were injected with stem cells in
      the tail vein. Rats of IP SCT group received IP cell therapy. Histological,
      histochemical, immunohistochemical and morphometric studies were performed.
      Obstructed bronchioles, overdistended alveoli, reduced type I pneumocytes,
      increased thickness of alveolar septa and vessels wall besides increased area% of
      collagen fibers regressed in response to IV and IP SCT. The improvement was more
      obvious in IV group. The area% of Prussion blue +ve and CD105 +ve cells was
      significantly higher in IV group. CONCLUSIONS: Cord blood MSC therapy proved
      definite amelioration of lung injury ending in fibrosis. The effect of IP SCT was
      slightly inferior to that of IV SCT, which may be overwhelmed by repeated IP
      injection.

PMID- 24921023
TI  - Myelo-enhancement by astragalus membranaceus in male albino rats with
      chemotherapy myelo-suppression. Histological and immunohistochemical study.
AB  - BACKGROUND AND OBJECTIVES: Myelosuppression is the most common toxicity
      encountered in the oncology clinic today. This study was planned to investigate
      the possible protective and therapeutic role of the traditional Chinese Medicinal
      Herb; Astragalus Membranaceus (AM), on chemotherapy-induced myelosuppression.
      METHODS AND RESULTS: This study was carried out on thirty six adult male albino
      rats. They were divided into: Group I Control Group (n=6) received a vehicle of
      phosphate buffered saline (PBS) solution. Group II (n=12) were injected I.P. with
      cyclophosphamide (CY) for 3 days (gIIa n =6) and continued for one more week to
      receive AM orally (gIIb n=6). Group III (n=6) received CY I.P. together with AM
      orally for 3 days. Group IV (n=12) received AM orally for one week (gIVa n=6) and
      continued for extra three days receiving CY I.P. with AM orally (gIVb n=6). Blood
      samples were analysed for Total Leucocytic Count and Lymphocytic Count. Counting
      of CD34 +ve cells in bone marrow was performed by flowcytometry. Bone marrow
      sections were subjected to H&E stain as well as immunohistochemical staining for
      anti- CD20 antibody. The mean area % of cellular bone marrow regions occupied by
      developing haemopoietic cells, mean area of fat cells and mean number of CD20
      immunopositive B lymphocytes in the bone marrow were measured by
      histomorphometric studies and statistically compared. AM proved to have a myelo
      protective and myelo-therapeutic capacity, evidenced at both laboratory and
      morphological levels. CONCLUSIONS: The greatest myelo-potentiating effect of AM
      was achieved when supplied before and together with CY therapy.

PMID- 24921024
TI  - Translational Research: Palatal-derived Ecto-mesenchymal Stem Cells from Human
      Palate: A New Hope for Alveolar Bone and Cranio-Facial Bone Reconstruction.
AB  - The management of facial defects has rapidly changed in the last decade.
      Functional and esthetic requirements have steadily increased along with the
      refinements of surgery. In the case of advanced atrophy or jaw defects, extensive
      horizontal and vertical bone augmentation is often unavoidable to enable patients
      to be fitted with implants. Loss of vertical alveolar bone height is the most
      common cause for a non primary stability of dental implants in adults. At
      present, there is no ideal therapeutic approach to cure loss of vertical alveolar
      bone height and achieve optimal pre-implantological bone regeneration before
      dental implant placement. Recently, it has been found that specific populations
      of stem cells and/or progenitor cells could be isolated from different dental
      resources, namely the dental follicle, the dental pulp and the periodontal
      ligament. Our research group has cultured palatal-derived stem cells (paldSCs) as
      dentospheres and further differentiated into various cells of the neuronal and
      osteogenic lineage, thereby demonstrating their stem cell state. In this
      publication will be shown whether paldSCs could be differentiated into the
      osteogenic lineage and, if so, whether these cells are able to regenerate
      alveolar bone tissue in vivo in an athymic rat model. Furthermore, using these
      data we have started a proof of principle clinical- and histological controlled
      study using stem cell-rich palatal tissues for improving the vertical alveolar
      bone augmentation in critical size defects. The initial results of the study
      demonstrate the feasibility of using stem cell-mediated tissue engineering to
      treat alveolar bone defects in humans. 

PMID- 24921025
TI  - Stem cells and niemann pick disease.
AB  - BACKGROUND AND OBJECTIVES: Niemann Pick A disease causes a progressive
      accumulation of sphyngomyelin in several organs and the survival of the patients
      is usually limited to three years. We describe the outcome of a patient suffering
      from Niemann Pick A disease, who first underwent an haploidentical bone marrow
      transplantation, and then intrathecal and I.V injections of mesenchymal cells.
      METHODS AND RESULTS: While the outcome of bone marrow transplantation was a
      complete failure, one month after the treatment with the mesenchymal cells the
      patient improved from the psychomotor and the parenchymal storage perspective.
      When hypersplenism was solved platelets rose quickly from 20,000 to
      120,000/microliter. CONCLUSIONS: Therefore cellular therapy should be considered
      as a possible choice of treatment of NPA disease.

PMID- 24921026
TI  - Histolgical and immunohistochemical study on the effect of stem cell therapy on
      bleomycin induced pulmonary fibrosis in albino rat.
AB  - AIM OF WORK: To demonstrate the bleomycin induced histological changes in the
      lung and the possible protective and/or therapeutic effect of stem cell therapy.
      MATERIALS AND METHODS: Study was carried out on 36 adult male albino rats,
      classified into 4 groups: group I (control), group II (bleomycin treated group),
      group III (early stem cell treated group: immediately after bleomycin), group IV
      (late stem cell treated group: 7 days after bleomycin). Sections were taken at
      the 14(th) day of experiment. stained with Hematoxylin and Eosin, Masson's
      trichrome, immunohistochemichal stains for alpha-SMA & PCNA. Sections were
      examined by light & immunofluroscent microscopy. Area percent of collagen fibers,
      area percent & optical density of alpha-SMA immunopositive cells were measured as
      well as the number of H&E and PCNA stained pneumocytes type II was counted.
      RESULTS: Group II showed, thickening of septa, extravasation of blood, dividing
      pneumocytes type II cells with acinar formation, cellular infiltration,
      fibroblast cells, almost complete loss of normal lung architecture in certain
      fields, consolidation and replacement of the lung tissue with fibrous tissue in
      other fields. Restoring of lung tissue with significant decrease in mean area %
      of collagen fibers, alpha-SMA immunopositive cells were detected in group III.
      CONCLUSIONS: Early treatment with bone marrow derived mesenchymal stem cells
      (BMSCs) immediately after bleomycin administration showed a significant reduction
      in fibrotic changes, however the late treatment with BMSCs (7 days) after
      bleomycin administration showed non significant results.

PMID- 24921027
TI  - In Vivo Roles of a Patient-Derived Induced Pluripotent Stem Cell Line (HD72-iPSC)
      in the YAC128 Model of Huntington's Disease.
AB  - Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients
      can provide immense opportunities to model human diseases, which may lead to
      develop novel therapeutics. Huntington's disease (HD) is a devastating
      neurodegenerative genetic disease, with no available therapeutic options at the
      moment. We recently reported the characteristics of a HD patient-derived iPSC
      carrying 72 CAG repeats (HD72-iPSC). In this study, we investigated the in vivo
      roles of HD72-iPSC in the YAC128 transgenic mice, a commonly used HD mouse model
      carrying 128 CAG repeats. To do this, we transplanted HD72-iPSC-derived neural
      precursors into the striatum of YAC128 mice bilaterally and observed a
      significant behavioral improvement in the grafted mice. Interestingly, the
      transplanted HD72-iPSC-derived neural precursors formed GABAeric neurons
      efficiently, but no EM48-positive protein aggregates were detected at 12 weeks
      after transplantation. Taken together, these results indicate no HD pathology was
      developed from the grafted cells, or no transmission of HD pathology from the
      host to the graft occurred at 12 weeks post-transplantation. 

PMID- 24921028
TI  - The Interrelationship between Diabetes and Depression.

PMID- 24921029
TI  - A primary care approach to myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are probably the most common hematologic
      malignancies in adults over the age of 60 and are a major source of morbidity and
      mortality among older age groups. Diagnosis and management of this chronic blood
      cancer has evolved significantly in recent years and there are Food and Drug
      Administration-approved therapies that can extend patients' life expectancy and
      improve quality of life. Primary care physicians (PCPs) are often involved in the
      process of diagnosis and follow-up of MDS patients, especially those in low-risk
      groups. They can therefore play an important role in improving patient care and
      quality of life by ensuring early referral and participating in supportive
      management. There is also a shortage of oncologists which increases the
      importance of the role of PCPs in management of MDS patients. In the face of
      limited resources, PCPs can improve access and quality of care in MDS patients.
      This article provides an overview of the common manifestations, diagnostic
      approaches, and therapeutic modalities of MDS for PCPs, with a focus on when to
      suspect MDS, when a referral is appropriate, and how to provide appropriate
      supportive care for patients diagnosed with MDS. 

PMID- 24921030
TI  - The effect of exercise on prevention of the common cold: a meta-analysis of
      randomized controlled trial studies.
AB  - BACKGROUND: Because there is no specific treatment for the common cold, many
      previous studies have focused on prevention of the common cold. There were some
      studies reporting that regular, moderate-intensity exercise increases immunity
      and prevents the common cold. We conducted a meta-analysis to determine the
      effects of exercise on prevention of the common cold. METHODS: We searched
      MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL),
      CINAHL for studies released through June 2013. We manually searched the
      references. Two authors independently extracted the data. To assess the risk of
      bias of included literature, Cochrane Collaboration's tool for assessing risk of
      bias was used. Review Manager ver. 5.2 (RevMan, Cochrane Collaboration) was used
      for statistical analysis. RESULTS: Four randomized controlled trials were
      identified. A total of 281 participants, 134 in the exercise group and 147 in the
      control group, were included. The effect of exercise on the prevention of the
      common cold had a relative risk (RR) of 0.73 (95% confidence interval [CI], 0.56
      to 0.95; I(2) = 7%). The mean difference of mean illness days between exercise
      group and control group was -3.50 (95% CI, -6.06 to -0.94; I(2) = 93%). In the
      subgroup analysis, the RR of under 16 weeks exercise was 0.79 (95% CI, 0.58 to
      1.08). CONCLUSION: In this meta-analysis, regular, moderate-intensity exercise
      may have an effect on the prevention of the common cold. But numbers of included
      studies and participants were too small and quality of included studies was
      relatively poor. Subsequent well-designed studies with larger sample size are
      needed to clarify the association.

PMID- 24921031
TI  - Diabetes and depressive symptoms in korean women: the fifth korean national
      health and nutrition examination survey (2010-2011).
AB  - BACKGROUND: The purpose of this study was to investigate the association between
      diabetes and depressive symptoms among Korean women. METHODS: We performed an
      analysis of data for 6,572 women aged 30 or over obtained from the Fifth Korean
      National Health and Nutrition Examination Survey conducted in 2010 to 2011. We
      examined the presence of depressive symptoms and the treatment of depression
      according to diabetes status. RESULTS: The presence of depressive symptoms was
      observed in 22.6% of subjects with diabetes. In the multiple logistic regression
      model, diabetes was associated with an increased risk of depressive symptoms
      (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.20 to 1.21) but the
      treatment of depression among diabetics was less common (OR, 0.54; 95% CI, 0.54
      to 0.55). Uncontrolled diabetes (glycosylated hemoglobin >= 7%) was associated
      with an increased risk of depressive symptoms (OR, 1.71; 95% CI, 1.69 to 1.73)
      among diabetics. CONCLUSION: Physicians should manage individuals with diabetes
      in consideration of the presence of depressive symptoms, especially in those with
      uncontrolled diabetes.

PMID- 24921032
TI  - Gallstones are Associated with Intima-Media Thickness of Common Carotid Arteries
      in Men.
AB  - BACKGROUND: The prevalence of gallstone disease is increasing in Korea. Gallstone
      disease and atherosclerosis share common risk factors. Ultrasonographic carotid
      intima-media thickness is an independent predictor of atherosclerosis. We
      measured the carotid intima-media thickness among men who had gallstones to
      establish the association between atherosclerosis and gallstones. METHODS: A
      total of 330 men who visited the health promotion center of the IS Hallym
      Hospital from January 2011 to July 2012 were recruited. Both abdomen and carotid
      ultrasonographies were performed. Demographic, anthropometric, and biochemical
      data were collected. RESULTS: The prevalence of gallstones was 6.6%. The carotid
      intima-media thickness, age, and body mass index were higher in subjects with
      gallstones (P < 0.05 for all). After Pearson correlation analysis, gallstone,
      age, body mass index, and fasting blood sugar were significantly associated with
      carotid intima-media thickness. A statistically positive association between
      gallstone and carotid intima-media thickness was demonstrated in a multivariate
      analysis adjusted for age, body mass index, and fasting blood sugar. CONCLUSION:
      Carotid intima-media thickness is higher in male subjects with gallstones,
      indicating that they are at greater risk for atherosclerosis.

PMID- 24921033
TI  - Association between Dyslipidemia and the Prevalence of Colon Polyps Based on a
      Health Evaluation of Subjects at a Hospital.
AB  - BACKGROUND: Colonic neoplasm is associated with western diet intake and physical
      inactivity. These life styles are also risk factors for dyslipidemia and
      metabolic syndrome. The aim of this study was to evaluate the association between
      dyslipidemia and the prevalence of colon polyps including colon adenoma as a
      precancerous lesion of colonic neoplasms. METHODS: We selected subjects
      undergoing a colonoscopy for health screening at the Health Promotion Center of
      Eulji General Hospital from January 2006 to June 2010. Subjects with histories of
      cancers, dyslipidemia treatment, and other intestinal diseases like Crohn's
      disease and ulcerative colitis were excluded. The total numbers of subjects
      included in the study was 605. Chi-square test and t-test and were used for the
      analysis. Additionally we used multivariate logistic regression to adjust for
      sex, age, smoking, drinking, and other risk factors. RESULTS: The prevalence of
      colon polyps was 48.70% and 28.05% in males and females, respectively. When
      adjusting for variables that included age, body mass index, hypertension,
      diabetes mellitus, smoking, drinking, and exercise, dyslipidemia was not
      significantly associated with the prevalence of colon polyps. However upon
      analyzing adenomatous colon polyps in men, dyslipidemias due to triglycerides and
      high density lipoproteins were significant factors (odds ratio [OR], 2.13;
      confidence interval [CI], 1.14 to 3.98; OR, 2.24; CI, 1.15 to 4.34,
      respectively). CONCLUSION: Dyslipidemia was not a significant factor in the
      prevalence of colon polyps. However it had a significant association with the
      prevalence of adenomatous colon polyps in men.

PMID- 24921034
TI  - Association between Physical Activity and Health-Related Quality of Life in
      Korean: The Korea National Health and Nutrition Examination Survey IV.
AB  - BACKGROUND: Numerous studies have identified that physical activity (PA) has
      positive influences on quality of life. However, there has been little domestic
      research about the relation of PA to health-related quality of life (HRQoL) among
      the general population. The purpose of this study was to evaluate the effect of
      PA on HRQoL in Korean adults aged 40 years or over. METHODS: This cross-sectional
      study was based on data acquired from the Korean National Health and Nutrition
      Examination Survey IV. Final study subjects were 10,392 adults aged 40 years or
      over. According to the severity and frequency of PA, the subjects were divided
      into three PA groups as follows: high-activity, mid-activity, and low-activity
      group. We compared the HRQoL estimated by the EuroQoL 5-dimension (EQ-5D), the EQ
      visual analogue scale (EQ-VAS), and EQ-5D index between three PA groups. RESULTS:
      The odds ratios for mid-activity group and high activity group compared with low
      activity group were significantly decreased in the dimension of mobility of EQ-5D
      (mid-activity group, 0.81 [0.69-0.94]; high activity group, 0.81 [0.67-0.99]). EQ
      VAS was decreased as PA level was lowered from high activity group and mid
      activity to low activity group. EQ-5D index was the highest in mid-activity group
      and the lowest in low activity group. CONCLUSION: PA above mid-activity group
      showed better HRQoL compared than low activity group.

PMID- 24921035
TI  - Epiglottic cyst incidentally discovered during screening endoscopy: a case report
      and review of literature.
AB  - From the endoscopists' point of view, although the main focus of upper
      gastrointestinal endoscopic examination is the esophagus, stomach, and duodenum
      (usually bulb and 2nd portion including ampulla of Vater), the portions of the
      upper airway may also be observed during insertion and withdrawal of the
      endoscope, such as pharynx and larynx. Thus, a variety of pathologic lesions of
      the upper airway can be encountered during upper endoscopy. Among these lesions,
      an epiglottic cyst is relatively uncommon. The cyst has no malignant potential
      and mostly remains asymptomatic in adults. However, if large enough, epiglottic
      cysts can compromise the airway and can be potentially life-threatening when an
      emergency endotracheal intubation is needed. Thus, patients may benefit from
      early detection and treatment of these relatively asymptomatic lesions. In this
      report, we present a case of epiglottic cyst in an asymptomatic adult
      incidentally found by family physician during screening endoscopy, which was
      successfully removed without complication, using a laryngoscopic carbon dioxide
      laser. 

PMID- 24921036
TI  - Comments on statistical issues in may 2014.

PMID- 24921038
TI  - Disubstituted Sialic Acid Ligands Targeting Siglecs CD33 and CD22 Associated with
      Myeloid Leukaemias and B Cell Lymphomas.
AB  - The siglec family of sialic acid-binding proteins are endocytic immune cell
      receptors that are recognized as potential targets for cell directed therapies.
      CD33 and CD22 are prototypical members and are validated candidates for targeting
      acute myeloid leukaemia and non-Hodgkin's lymphomas due to their restricted
      expression on myeloid cells and B-cells, respectively. While nanoparticles
      decorated with high affinity siglec ligands represent an attractive platform for
      delivery of therapeutic agents to these cells, a lack of ligands with suitable
      affinity and/or selectivity has hampered progress. Herein we describe selective
      ligands for both of these siglecs, which when displayed on liposomal
      nanoparticles, can efficiently target the cells expressing them in peripheral
      human blood. Key to their identification was the development of a facile method
      for chemo-enzymatic synthesis of disubstituted sialic acid analogues, combined
      with iterative rounds of synthesis and rapid functional analysis using glycan
      microarrays.

PMID- 24921040
TI  - A Regioselective Synthesis of the Dephospho DIthiolene Protected Molybdopterin.
AB  - The molybdopterin (MPT) is a complex molecule, made out of three distinctly
      different components. A retrosynthetic analysis provides a possible route for its
      synthesis that utilizes the coupling of a diamine with an osone analog. A
      regioselective condensation of the diamine with an osone affords the dephospho
      MPT, which has been characterized by NMR and IR spectroscopies, as well as high
      resolution mass spectrometry.

PMID- 24921039
TI  - Area-dependent time courses of brain activation during video-induced symptom
      provocation in social anxiety disorder.
AB  - BACKGROUND: Previous functional imaging studies using symptom provocation in
      patients with social anxiety disorder (SAD) reported inconsistent findings, which
      might be at least partially related to different time-dependent activation
      profiles in different brain areas. In the present functional magnetic resonance
      imaging study, we used a novel video-based symptom provocation design in order to
      investigate the magnitude and time course of activation in different brain areas
      in 20 SAD patients and 20 healthy controls. RESULTS: The disorder-related videos
      induced increased anxiety in patients with SAD as compared to healthy controls.
      Analyses of brain activation to disorder-related versus neutral video clips
      revealed amygdala activation during the first but not during the second half of
      the clips in patients as compared to controls. In contrast, the activation in the
      insula showed a reversed pattern with increased activation during the second but
      not during the first half of the video clips. Furthermore, a cluster in the
      anterior dorsal anterior cingulate cortex showed a sustained response for the
      entire duration of the videos. CONCLUSIONS: The present findings suggest that
      different regions of the fear network show differential temporal response
      patterns during video-induced symptom provocation in SAD. While the amygdala is
      involved during initial threat processing, the insula seems to be more involved
      during subsequent anxiety responses. In accordance with cognitive models of SAD,
      a medial prefrontal region engaged in emotional-cognitive interactions is
      generally hyperactivated.

PMID- 24921041
TI  - Moving in extreme environments: what's extreme and who decides?
AB  - Humans work, rest and play in immensely varied extreme environments. The term
      'extreme' typically refers to insufficiency or excess of one or more stressors,
      such as thermal energy or gravity. Individuals' behavioural and physiological
      capacity to endure and enjoy such environments varies immensely. Adverse effects
      of acute exposure to these environments are readily identifiable (e.g. heat
      stroke or bone fracture), whereas adverse effects of chronic exposure (e.g.
      stress fractures or osteoporosis) may be as important but much less discernable.
      Modern societies have increasingly sought to protect people from such stressors
      and, in that way, minimise their adverse effects. Regulations are thus
      established, and advice is provided on what is 'acceptable' exposure. Examples
      include work/rest cycles in the heat, hydration regimes, rates of ascent to and
      duration of stay at altitude and diving depth. While usually valuable and well
      intentioned, it is important to realise the breadth and importance of limitations
      associated with such guidelines. Regulations and advisories leave less room for
      self-determination, learning and perhaps adaptation. Regulations based on stress
      (e.g. work/rest cycles relative to WBGT) are more practical but less direct than
      those based on strain (e.g. core temperature), but even the latter can be
      substantively limited (e.g. by lack of criterion validation and allowance for
      behavioural regulation in the research on which they are based). Extreme
      Physiology & Medicine is publishing a series of reviews aimed at critically
      examining the issues involved with self- versus regulation-controlled human
      movement acutely and chronically in extreme environments. These papers, arising
      from a research symposium in 2013, are about the impact of people engaging in
      such environments and the effect of rules and guidelines on their safety,
      enjoyment, autonomy and productivity. The reviews will cover occupational heat
      stress, sporting heat stress, hydration, diving, extreme loading, chronic
      unloading and high altitude. Ramifications include factors such as health and
      safety, productivity, enjoyment and autonomy, acute and chronic protection and
      optimising adaptation. 

PMID- 24921042
TI  - Moving in extreme environments: open water swimming in cold and warm water.
AB  - Open water swimming (OWS), either 'wild' such as river swimming or competitive,
      is a fast growing pastime as well as a part of events such as triathlons. Little
      evidence is available on which to base high and low water temperature limits.
      Also, due to factors such as acclimatisation, which disassociates thermal
      sensation and comfort from thermal state, individuals cannot be left to monitor
      their own physical condition during swims. Deaths have occurred during OWS; these
      have been due to not only thermal responses but also cardiac problems. This
      paper, which is part of a series on 'Moving in Extreme Environments', briefly
      reviews current understanding in pertinent topics associated with OWS. Guidelines
      are presented for the organisation of open water events to minimise risk, and it
      is concluded that more information on the responses to immersion in cold and warm
      water, the causes of the individual variation in these responses and the
      precursors to the cardiac events that appear to be the primary cause of death in
      OWS events will help make this enjoyable sport even safer. 

PMID- 24921043
TI  - Randomized controlled trials in frontotemporal dementia: cognitive and behavioral
      outcomes.
AB  - Progress has been made in understanding the genetics and molecular biology of
      frontotemporal dementia (FTD). Targets for intervention have been identified,
      therapies are being developed, and clinical trials are advancing. A major
      challenge for FTD research is that multiple underlying pathologies can be
      associated with heterogeneous phenotypes. The neuropsychological profiles
      associated with FTD spectrum disorders often include executive dysfunction,
      language impairments and behavioral disturbance. Behavioral variant FTD is
      characterized by an initial presentation of changes in personality, behavior
      and/or emotion, which are often difficult to objectively capture using
      traditional neuropsychological measures. The two principal language variants of
      FTD are Progressive Nonfluent Aphasia (PNFA) with predominant agrammatic/non
      fluent impairments and Semantic Dementia (SD) with semantic impairments and
      visual agnosia. Selection of appropriate endpoints for clinical trials is
      critical to ensure that the measures are adequately sensitive to detect change,
      yet specific enough to isolate signal from noise, and acceptable to regulatory
      agencies. Given the anticipated potential for small effect sizes, measures must
      be able to identify small incremental changes over time. It is also imperative
      that the measures provide adequate coverage of the constructs or behaviors of
      interest. Selected outcome measures should be suitable for repeat administration,
      yet relatively robust to practice effects to ensure that observed changes reflect
      true signal variance and not residual effects due to repeated measurement or poor
      reliability. To facilitate widespread adoption as an endpoint, measures should be
      readily accessible. We provide several examples of potential global, composite,
      and individual cognitive measures, as well as behavioral measures promising for
      FTD trials. Development and application of appropriate trial outcomes is
      critically important to success in advancing new treatments for FTD patients. 

PMID- 24921044
TI  - Adherence to Immunoprophylaxis Regimens for Respiratory Syncytial Virus Infection
      in Insured and Medicaid Populations.
AB  - BACKGROUND: Immunoprophylaxis is the only pharmaceutical intervention for
      mitigating respiratory syncytial virus (RSV) infection. Patient level data on
      adherence to American Academy of Pediatrics (AAP) immunoprophylaxis
      recommendations are limited. This study characterizes adherence to AAP guidelines
      in privately insured and Medicaid populations. METHODS: We performed a
      retrospective birth cohort study of 211 174 privately insured children in
      Northern California; and 458 837 publicly insured children in Tennessee born
      between January 1, 1996 and December 31, 2008. Adherence to the AAP guideline was
      defined for eligible infants as the number of doses of RSV immunoprophylaxis
      administered over the number recommended for 4 mutually exclusive eligibility
      groups: chronic lung disease, prematurity <29 weeks, prematurity <32 weeks, and
      other eligibility. RESULTS: We identified 3456 California (Kaiser Permanente
      Northern California [KPNC]) and 12 251 Tennessee (Tennessee Medicaid [TennCare])
      infants meeting AAP eligibility criteria. Immunoprophylaxis administration
      increased over the study period, from 15% for all eligible groups in 1998 to 54%
      in 2007. Adherence was highest among babies with chronic lung disease (KPNC 67%
      and TennCare 55%). Nonadherence (0% adherence) was greatest among infants of
      African American mothers (adjusted odds ratio [AOR] = 1.32; 95% confidence
      interval [CI] = .98-1.78); those with mothers with less than a high school
      education (AOR = 1.58; CI = 1.09-2.30) in KPNC; and in infants of Hispanic
      mothers in TennCare (AOR = 1.65; CI = 1.24-2.20). In KPNC, 0.11% of ineligible
      term infants and 5% of ineligible premature infants received immunoprophylaxis;
      the corresponding proportions in TennCare were 1% and 11%. CONCLUSIONS: Overall
      adherence with AAP guidelines has increased over time. Considerable overuse and
      underuse of immunoprophylaxis are evident with identifiable risk groups to target
      for improvement.

PMID- 24921045
TI  - Amino acid digestibility in low-fat distillers dried grains with solubles fed to
      growing pigs.
AB  - The objective of this experiment was to determine the standardized ileal
      digestibility (SID) of amino acids (AA) in 3 sources of distillers dried grains
      with solubles (DDGS) with different concentrations of fat. Twelve growing barrows
      (initial body weight: 76.1 [Formula: see text] 6.2 kg) were randomly allotted to
      a replicated 6 * 4 Youden square design with 6 diets and 4 periods. The fat
      content of the 3 sources of DDGS were 11.5, 7.5, and 6.9% respectively. Diets
      contained 60% DDGS and fat concentration of the diets were 7.5, 5.2, and 5.2%,
      respectively. Two additional diets containing the 2 sources of DDGS with 7.5 and
      6.9% fat were also formulated, and corn oil was added to these diets to increase
      the concentration of fat in the diets to levels that were calculated to be
      similar to the diet containing conventional DDGS with 11.5% fat. A N-free diet
      was also formulated to calculate endogenous losses of crude protein (CP) and AA
      from the pigs. Pigs were fed experimental diets during four 7-d periods. The
      first 5 d of each period were an adaptation period and ileal digesta were
      collected on d 6 and 7 of each period. The apparent ileal digestibililty (AID)
      and SID of CP and all indispensable AA, except AID Pro and SID of Trp, were
      greater (P < 0.01) in conventional DDGS than in the 2 sources of DDGS with
      reduced fat. Adding oil to the diets containing the 2 sources of DDGS with
      reduced fat did not consistently increase SID of AA. In conclusion, conventional
      DDGS has greater SID values for most AA compared with DDGS that contains less fat
      and inclusion of additional oil to diets containing low-fat DDGS does not
      increase AID or SID of AA. The lower AA digestibility in low-fat DDGS could not
      be overcome by the inclusion of additional fat to the diets. 

PMID- 24921046
TI  - Focused ultrasound to displace renal calculi: threshold for tissue injury.
AB  - BACKGROUND: The global prevalence and incidence of renal calculi is reported to
      be increasing. Of the patients that undergo surgical intervention, nearly half
      experience symptomatic complications associated with stone fragments that are not
      passed and require follow-up surgical intervention. In a clinical simulation
      using a clinical prototype, ultrasonic propulsion was proven effective at
      repositioning kidney stones in pigs. The use of ultrasound to reposition smaller
      stones or stone fragments to a location that facilitates spontaneous clearance
      could therefore improve stone-free rates. The goal of this study was to determine
      an injury threshold under which stones could be safely repositioned. METHODS:
      Kidneys of 28 domestic swine were treated with exposures that ranged in duty
      cycle from 0%-100% and spatial peak pulse average intensities up to 30 kW/cm(2)
      for a total duration of 10 min. The kidneys were processed for morphological
      analysis and evaluated for injury by experts blinded to the exposure conditions.
      RESULTS: At a duty cycle of 3.3%, a spatial peak intensity threshold of 16,620
      W/cm(2) was needed before a statistically significant portion of the samples
      showed injury. This is nearly seven times the 2,400-W/cm(2) maximum output of the
      clinical prototype used to move the stones effectively in pigs. CONCLUSIONS: The
      data obtained from this study show that exposure of kidneys to ultrasonic
      propulsion for displacing renal calculi is well below the threshold for tissue
      injury.

PMID- 24921047
TI  - Ultrasound-enhanced ocular delivery of dexamethasone sodium phosphate: an in vivo
      study.
AB  - BACKGROUND: The eye's unique anatomy and its physiological and anatomical
      barriers can limit effective drug delivery into the eye. METHODS: An in vivo
      study was designed to determine the effectiveness and safety of ultrasound
      application in enhancing drug delivery in a rabbit model. Permeability of a
      steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in
      ultrasound- and sham-treated cases. For this study, an eye cup filled with
      dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied
      at intensity of 0.8 W/cm(2) and frequency of 400 or 600 kHz for 5 min. The drug
      concentration in aqueous humor samples, collected 90 min after the treatment, was
      determined using chromatography methods. Light microscopy observations were done
      to determine the structural changes in the cornea as a result of ultrasound
      application. RESULTS: An increase in drug concentration in aqueous humor samples
      of 2.8 times (p < 0.05) with ultrasound application at 400 kHz and 2.4 times (p <
      0.01) with ultrasound application at 600 kHz was observed as compared to sham
      treated samples. Histological analysis showed that the structural changes in the
      corneas exposed to ultrasound predominantly consisted of minor epithelial
      disorganization. CONCLUSIONS: Ultrasound application enhanced the delivery of an
      anti-inflammatory ocular drug, dexamethasone sodium phosphate, through the cornea
      in vivo. Ultrasound-enhanced ocular drug delivery appears to be a promising area
      of research with a potential future application in a clinical setting.

PMID- 24921048
TI  - Magnetic resonance-guided focused ultrasound treatment of facet joint pain:
      summary of preclinical phase.
AB  - STUDY DESIGN: A phantom experiment, two thermocouple experiments, three in vivo
      pig experiments, and a simulated treatment on a healthy human volunteer were
      conducted to test the feasibility, safety, and efficacy of magnetic resonance
      guided focused ultrasound (MRgFUS) for treating facet joint pain. OBJECTIVE: The
      goal of the current study was to develop a novel method for accurate and safe
      noninvasive facet joint ablation using MRgFUS. SUMMARY OF BACKGROUND DATA: Facet
      joints are a common source of chronic back pain. Direct facet joint interventions
      include medial branch nerve ablation and intra-articular injections, which are
      widely used, but limited in the short and long term. MRgFUS is a breakthrough
      technology that enables accurate delivery of high-intensity focused ultrasound
      energy to create a localized temperature rise for tissue ablation, using MR
      guidance for treatment planning and real-time feedback. METHODS: We validated the
      feasibility, safety, and efficacy of MRgFUS for facet joint ablation using the
      ExAblate 2000(r) System (InSightec Ltd., Tirat Carmel, Israel) and confirmed the
      system's ability to ablate the edge of the facet joint and all terminal nerves
      innervating the joint. A phantom experiment, two thermocouple experiments, three
      in vivo pig experiments, and a simulated treatment on a healthy human volunteer
      were conducted. RESULTS: The experiments showed that targeting the facet joint
      with energies of 150-450 J provides controlled and accurate heating at the facet
      joint edge without penetration to the vertebral body, spinal canal, or root
      foramina. Treating with reduced diameter of the acoustic beam is recommended
      since a narrower beam improves access to the targeted areas. CONCLUSIONS: MRgFUS
      can safely and effectively target and ablate the facet joint. These results are
      highly significant, given that this is the first study to demonstrate the
      potential of MRgFUS to treat facet joint pain.

PMID- 24921050
TI  - Photoactive Electrospun Polymeric Meshes: Spatiotemporally Wetting of Textured 3
      Dimensional Structures.
AB  - The preparation, characterization, and use of a UV responsive non-woven nanofiber
      polymeric mesh is reported that transitions from being hydrophobic to
      hydrophilic. Three distinct wetting profiles are observed during the wetting
      process. 3D hydrophilic cavities were created within the hydrophobic bulk
      material by using a photo mask to control the geometry and UV exposure time to
      control the depth of the region.

PMID- 24921051
TI  - Biodegradation of cyanide by a new isolated strain under alkaline conditions and
      optimization by response surface methodology (RSM).
AB  - BACKGROUND: Biodegradation of free cyanide from industrial wastewaters has been
      proven as a viable and robust method for treatment of wastewaters containing
      cyanide. RESULTS: Cyanide degrading bacteria were isolated from a wastewater
      treatment plant for coke-oven-gas condensate by enrichment culture technique.
      Five strains were able to use cyanide as the sole nitrogen source under alkaline
      conditions and among them; one strain (C2) was selected for further studies on
      the basis of the higher efficiency of cyanide degradation. The bacterium was able
      to tolerate free cyanide at concentrations of up to 500 ppm which makes it a good
      potentially candidate for the biological treatment of cyanide contaminated
      residues. Cyanide degradation corresponded with growth and reached a maximum
      level 96% during the exponential phase. The highest growth rate (1.23 * 10(8))
      was obtained on day 4 of the incubation time. Both glucose and fructose were
      suitable carbon sources for cyanotrophic growth. No growth was detected in media
      with cyanide as the sole carbon source. Four control factors including, pH,
      temperature, agitation speed and glucose concentration were optimized according
      to central composite design in response surface method. Cyanide degradation was
      optimum at 34.2 degrees C, pH 10.3 and glucose concentration 0.44 (g/l).
      CONCLUSIONS: Bacterial species degrade cyanide into less toxic products as they
      are able to use the cyanide as a nitrogen source, forming ammonia and carbon
      dioxide as end products. Alkaliphilic bacterial strains screened in this study
      evidentially showed the potential to possess degradative activities that can be
      harnessed to remediate cyanide wastes.

PMID- 24921049
TI  - Rare Earth Nanoprobes for Functional Biomolecular Imaging and Theranostics.
AB  - Contrast agents designed to visualize the molecular mechanisms underlying cancer
      pathogenesis and progression have deepened our understanding of disease
      complexity and accelerated the development of enhanced drug strategies targeted
      to specific biochemical pathways. For the next generation probes and imaging
      systems to be viable, they must exhibit enhanced sensitivity and robust
      quantitation of morphologic and contrast features, while offering the ability to
      resolve the disease-specific molecular signatures that may be critical to
      reconstitute a more comprehensive portrait of pathobiology. This feature article
      provides an overview on the design and advancements of emerging biomedical
      optical probes in general and evaluates the promise of rare earth nanoprobes, in
      particular, for molecular imaging and theranostics. Combined with new
      breakthroughs in nanoscale probe configurations, and improved dopant
      compositions, and multimodal infrared optical imaging, rare-earth nanoprobes can
      be used to address a wide variety of biomedical challenges, including deep tissue
      imaging, real-time drug delivery tracking and multispectral molecular profiling.

PMID- 24921052
TI  - The digital version of JPIS offers more than ever.

PMID- 24921053
TI  - Long-term implant success at the Academy for Oral Implantology: 8-year follow-up
      and risk factor analysis.
AB  - PURPOSE: Rehabilitation of the incomplete dentition by means of osseointegrated
      dental implants represents a highly predictable and widespread therapy; however,
      little is known about potential risk factors that may impair long-term implant
      success. METHODS: From 2004 to 2012, a total of 13,147 implants were placed in
      4,316 patients at the Academy for Oral Implantology in Vienna. The survival rates
      after 8 years of follow-up were computed using the Kaplan-Meier method, and the
      impact of patient- and implant-related risk factors was assessed. RESULTS:
      Overall implant survival was 97% and was not associated with implant length
      (P=0.930), implant diameter (P=0.704), jaw location (P=0.545), implant position
      (P=0.450), local bone quality (P=0.398), previous bone augmentation surgery
      (P=0.617), or patient-related factors including osteoporosis (P=0.661), age
      (P=0.575), or diabetes mellitus (P=0.928). However, smoking increased the risk of
      implant failure by 3 folds (P<0.001) and a positive history of periodontal
      disease doubled the failure risk (P=0.001). CONCLUSIONS: Summing up the long-term
      results of well over 10,000 implants at the Academy for Oral Implantology in
      Vienna it can be concluded that there is only a limited number of patients that
      do not qualify for implant therapy and may thus not benefit from improved quality
      of life associated with fixed implant-retained prostheses.

PMID- 24921054
TI  - Improvement in periodontal healing after periodontal surgery supported by
      nutritional supplement drinks.
AB  - PURPOSE: The aim of this study was to determine the effects of nutritional
      supplements on periodontal health and tooth mobility after surgery. METHODS:
      Patients were randomly assigned to an intervention group who consumed nutritional
      supplement drinks for 8 weeks, while the placebo group did not receive any such
      supplements. The gingival index (GI) and tooth mobility were measured at baseline
      and at 1, 4, and 8 weeks. In addition, the oral health impact profile-14 and
      anthropometric measurements along with loss of appetite and dietary intake were
      assessed at baseline and 8 weeks. RESULTS: At 1 week, GI values were reduced in
      the intervention group (P<0.05), and tooth mobility had increased, but to a
      lesser extent in the intervention group (P<0.05). At 8 weeks, the intakes of
      protein, vitamins A and B1, and niacin were increased in the intervention group.
      CONCLUSIONS: These results demonstrate that nutritional supplementation improves
      early periodontal healing after surgery.

PMID- 24921055
TI  - Effects of scaling and root planing with or without a local drug delivery system
      on the gingival crevicular fluid leptin level in chronic periodontitis patients:
      a clinico-biochemical study.
AB  - PURPOSE: The present split mouth study evaluates the effect of nonsurgical
      periodontal treatment on the gingival crevicular fluid (GCF) leptin level in
      chronic periodontitis. METHODS: Ninety sites from 30 nonobese chronic
      periodontitis patients were selected and divided as follows: group I, 30 healthy
      sites receiving no treatment; group II, 30 periodontitis sites receiving scaling
      and root planing (SRP); and group III, 30 periodontitis sites receiving SRP with
      tetracycline local drug delivery. At baseline, after GCF sampling and clinical
      parameter recording, the assigned treatment was performed for the study groups.
      During recall visits, GCF sampling followed by clinical parameter recording was
      done for groups II and III. RESULTS: Reductions in the probing depth and the
      clinical attachment level (CAL) were highly significant at different time
      intervals (except between day 0 and 45) in both groups II and III. Upon
      comparison, group III showed significant gain in CAL between day 0 and 15 and
      between day 0 and 45. After treatment, the reduction in the GCF leptin level was
      more significant in group III than in group II at day 15 but re-elevated almost
      to the pretreatment levels at day 45. CONCLUSIONS: Nonsurgical periodontal
      therapies were not effective in maintaining stable reduction in the GCF leptin
      level during the study period.

PMID- 24921056
TI  - Evaluation of interleukin-1beta and 8 in gutka chewers with periodontitis among a
      rural Indian population.
AB  - PURPOSE: Smokeless tobacco-based oral-use products like gutka are popular in
      India. Gutka usage leads to increased periodontal destruction and inflammation;
      however, the relevant mechanism remains unknown. This study aimed to elucidate
      the role of gutka in periodontitis by examining its effect on the levels of
      interleukin (IL) 1beta and IL-8 from the gingival crevicular fluid (GCF).
      METHODS: A total of 45 patients were enrolled in this study. Thirty patients with
      periodontitis (15 gutka chewers [GCP] and 15 nongutka chewers [NGC]) and 15
      periodontally healthy controls (HC) were selected. The full-mouth plaque index
      (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL),
      and recession (RC) were recorded. The IL-1beta and IL-8 levels in the GCF of all
      subjects were assessed through an enzyme-linked immunosorbent assay (Quantikine).
      RESULTS: The IL-1beta and IL-8 levels were not significantly higher in the GCP
      group (IL-1beta, 369.01+/-273.44 uL; IL-8, 205.97+/-196.78 uL) as compared to
      those in the NGC group (IL-1beta, 195.57+/-96.85 uL; IL-8, 178.61+/-149.35 uL).
      More gingival RC and loss of attachment was seen among the GCP group (RC: 2.02+/
      0.31, P=0.013; CAL: 4.60+/-0.56, P<0.001) than among the NGC group (RC, 1.21+/
      1.15; CAL, 3.70+/-0.32); however, PD was deeper among the NGC subjects (P=0.002).
      PI and GI were significantly higher for the periodontitis group (P<0.001) when
      compared to the HC, but there was no difference among gutka chewers and non
      chewers (P=0.22 and P=0.89). A positive correlation was found between the IL-8
      levels and the duration of gutka chewing (r=-0.64, P<0.01). CONCLUSIONS: Gutka
      chewing leads to increased gingival RC and clinical loss of attachment. There was
      no effect seen in the proinflammatory cytokine levels in the GCF of gutka users.

PMID- 24921057
TI  - A randomized clinical trial to evaluate and compare the efficacy of triphala
      mouthwash with 0.2% chlorhexidine in hospitalized patients with periodontal
      diseases.
AB  - PURPOSE: Triphala is a combination of three medicinal plants, extensively used in
      Ayurveda since ancient times. Triphala mouthwash is used in the treatment of
      periodontal diseases because of its antimicrobial and antioxidant properties. The
      aim of this study is to compare the efficacy of triphala mouthwash with 0.2%
      chlorhexidine in hospitalized periodontal disease patients. METHODS: In this
      double-blind, randomized, multicenter clinical trial, 120 patients were equally
      divided into three groups. Patients in group A were advised to rinse their mouths
      with 10 mL of distilled water, group B with 0.2% chlorhexidine, and group C with
      triphala mouthwash for 1 minute twice daily for two weeks. The plaque index (PI)
      and the gingival index (GI) were recorded on the first and the fifteenth day.
      RESULTS: There was no significant difference when the efficacy of triphala was
      compared with 0.2% chlorhexidine in hospitalized patients with periodontal
      disease. However, a statistically significant difference was observed in PI and
      GI when both group B and group C were compared with group A and also within
      groups B and C, after 15 days (P<0.05). CONCLUSIONS: The triphala mouthwash
      (herbal) is an effective antiplaque agent like 0.2% chlorhexidine. It is
      significantly useful in reducing plaque accumulation and gingival inflammation,
      thereby controlling periodontal diseases in every patient. It is also cost
      effective, easily available, and well tolerable with no reported side effects.

PMID- 24921058
TI  - Receptor activator of nuclear factor kappa-B gene polymorphisms in Iranian
      periodontitis and peri-implantitis patients.
AB  - PURPOSE: Peri-implantitis and periodontitis are inflammatory and infectious
      diseases of implant and tooth-supporting tissues. Recently, the role of gene
      polymorphisms of immune response components in the relevant pathogenesis has been
      investigated. The present study was the first to evaluate the relationship
      between two known single nucleotide polymorphisms (SNPs) of the receptor
      activator of nuclear factor kappa-beta (RANK) gene (rs3018362 and rs35211496) in
      chronic periodontitis and peri-implantitis patients in an Iranian population.
      METHODS: Eighty-one periodontally healthy patients, 38 patients with peri
      implantitis, and 74 patients with chronic periodontitis were enrolled in this
      study. DNA was extracted from blood arm vein samples by using Miller's salting
      out technique according to the manufacturer's instructions given in the
      extraction kit. The concentration of DNA samples was measured using a
      spectrophotometer. The genetic polymorphisms of the RANK gene were evaluated
      using a competitive allele specific polymerase chain reaction (KBioscience allele
      specific PCR) technique. Differences in the frequencies of genotypes and alleles
      in the diseased and healthy groups were analyzed using chi-squared statistical
      tests (P<0.05). RESULTS: Analysis of rs35211496 revealed statistically
      significant differences in the expression of the TT, TC, and CC genotypes among
      the three groups (P=0.00). No statistically significant difference was detected
      in this respect between the control group and the chronic periodontitis group.
      The expression of the GG, GA, and AA genotypes and allele frequencies (rs3018362)
      showed no statistically significant difference among the three groups (P=0.21).
      CONCLUSIONS: The results of this study indicate that the CC genotype of the
      rs35211496 RANK gene polymorphism was significantly associated with peri
      implantitis and may be considered a genetic determinant for peri-implantitis, but
      this needs to be confirmed by further studies in other populations.

PMID- 24921059
TI  - Anterior maxillary defect reconstruction with a staged bilateral rotated palatal
      graft.
AB  - PURPOSE: In the anterior maxilla, hard and soft tissue augmentations are
      sometimes required to meet esthetic and functional demands. In such cases,
      primary soft tissue closure after bone grafting procedures is indispensable for a
      successful outcome. This report describes a simple method for soft tissue
      coverage of a guided bone regeneration (GBR) site using the double-rotated
      palatal subepithelial connective tissue graft (RPSCTG) technique for a maxillary
      anterior defect. METHODS: We present a 60-year-old man with a defect in the
      anterior maxilla requiring hard and soft tissue augmentations. The bone graft
      materials were filled above the alveolar defect and a titanium-reinforced
      nonresorbable membrane was placed to cover the graft materials. We used the
      RPSCTG technique to achieve primary soft tissue closure over the graft materials
      and the barrier membrane. Additional soft tissue augmentation using a
      contralateral RPSCTG and membrane removal were simultaneously performed 7 weeks
      after the stage 1 surgery to establish more abundant soft tissue architecture.
      RESULTS: Flap necrosis occurred after the stage 1 surgery. Signs of infection or
      suppuration were not observed in the donor or recipient sites after the stage 2
      surgery. These procedures enhanced the alveolar ridge volume, increased the
      amount of keratinized tissue, and improved the esthetic profile for restorative
      treatment. CONCLUSIONS: The use of RPSCTG could assist the soft tissue closure of
      the GBR sites because it provides sufficient soft tissue thickness, an ample
      vascular supply, protection of anatomical structures, and patient comfort. The
      treatment outcome was acceptable, despite membrane exposure, and the RPSCTG
      allowed for vitalization and harmonization with the recipient tissue.

PMID- 24921060
TI  - Maternal differences and birth outcome disparities: Diversity within a high risk
      prenatal clinic.
AB  - BACKGROUND: We examined the influence of race/ethnicity on appointment
      attendance, maternal psychiatric and medical diagnoses, and birth outcomes within
      a diverse, low income, high risk pregnant population to determine whether birth
      outcome disparities would be lessened in a sample with high biopsychosocial risk
      across all groups. METHODS: Data were retrospectively obtained on all women
      scheduled for appointments in the San Francisco Genera Hospital (SFGH) High-Risk
      Obstetrics (HROB) clinic during a three-month period. General linear model and
      logistic regression procedures were used to examine the associations of
      race/ethnicity with maternal characteristics, clinic attendance, and birth
      outcomes. RESULTS: Our sample included 202 maternal-infant pairs (Hispanic 57%,
      Black 16%, Asian 15%, White 12%). Racial/ethnic differences were seen in language
      (p < .001), gravidity (p < .001), parity (p = .005), appointment attendance (p <
      .001), diabetes (p = .005), psychiatric diagnosis (p = .02), illicit drug use (p
      < .001), smoking (p < .001). These maternal characteristics, including rate of
      attendance at specialized prenatal appointments, did not predict birth outcomes
      with the exception of an association between diabetes and earlier gestational age
      (p = .03). In contrast, Black maternal race/ethnicity was associated with earlier
      gestational age at birth (p = .004) and lower birth weight (p < .001) compared to
      Whites. CONCLUSIONS: Within a diverse maternal population of high biopsychosocial
      risk, racial/ethnic disparities in birth outcomes persist. These disparities have
      implications for infant health trajectory throughout the lifecourse and for
      intervention implementation in high risk groups.

PMID- 24921061
TI  - Novel Drugs of Abuse: A Snapshot of an Evolving Marketplace.
AB  - BACKGROUND & OBJECTIVES: Over the past decade, non-medical use of novel drugs has
      proliferated worldwide. In most cases these are synthetic drugs first synthesized
      in academic or pharmaceutical laboratories for research or drug development
      purposes, but also include naturally occurring substances that do not fit the
      typical pharmacological or behavioral profile of traditional illicit substances.
      Perhaps most unique to this generation of new drugs is that they are being sold
      over the counter and on the Internet as "legal highs" or substitutes for
      traditional illicit drugs such as cannabis, cocaine, amphetamines, MDMA, and LSD.
      The purpose of this review is to provide an overview of novel drugs in current
      use, including the epidemiology of use and toxicologic and pharmacological
      properties, and to offer some guidelines to clinicians who see patients
      experiencing adverse effects from these drugs. METHOD: We review the known
      scientific literature on recently introduced synthetic drug types, synthetic
      cannabinoids and synthetic cathinones, and the hallucinogen Salvia divinorum.
      RESULTS: These substances comprise part of a rapidly evolving and controversial
      drug market that has challenged definitions of what is legal and illegal, has
      benefitted from open commercial sales without regulatory oversight, and is
      noteworthy for the pace at which new substances are introduced. CONCLUSIONS: This
      emerging trend in substance use presents significant and unique public health and
      criminal justice challenges. At this time, these substances are not detected in
      routine drug screens and substance-specific treatment for cases of use-related
      toxicity are not available. Clinicians are encouraged to learn characteristic
      signs associated with misuse of novel drugs to recognize cases in their practice,
      and are recommended to use a symptom-specific approach for treatment in each
      case.

PMID- 24921062
TI  - Nonlinear photoacoustic signal amplification from single targets in absorption
      background.
AB  - Photoacoustic (PA) detection of single absorbing targets such as nanoparticles or
      cells can be limited by absorption background. We show here that this problem can
      be overcome by using the nonlinear photoacoustics based on the differences in PA
      signal dependences on the laser energy from targets and background. Among
      different nonlinear phenomena, we focused on laser generation of nanobubbles as
      more efficient PA signal amplifiers from strongly absorbing, highly localized
      targets in the presence of spatially homogenous absorption background generating
      linear signals only. This approach was demonstrated by using nonlinear PA flow
      cytometry platform for label-free detection of circulating melanoma cells in
      blood background in vitro and in vivo. Nonlinearly amplified PA signals from
      overheated melanin nanoclusters in melanoma cells became detectable above still
      linear blood background. Nonlinear nanobubble-based photoacoustics provide new
      opportunities to significantly (5-20-fold) increase PA contrast of single
      nanoparticles, cells, viruses and bacteria in complex biological environments.

PMID- 24921063
TI  - Building a flagellum in biological outer space.
AB  - Flagella, the rotary propellers on the surface of bacteria, present a paradigm
      for how cells build and operate complex molecular 'nanomachines'. Flagella grow
      at a constant rate to extend several times the length of the cell, and this is
      achieved by thousands of secreted structural subunits transiting through a
      central channel in the lengthening flagellum to incorporate into the nascent
      structure at the distant extending tip. A great mystery has been how flagella can
      assemble far outside the cell where there is no conventional energy supply to
      fuel their growth. Recent work published by Evans et al. [Nature (2013) 504: 287
      290], has gone some way towards solving this puzzle, presenting a simple and
      elegant transit mechanism in which growth is powered by the subunits them selves
      as they link head-to-tail in a chain that is pulled through the length of the
      growing structure to the tip. This new mechanism answers an old question and may
      have resonance in other assembly processes.

PMID- 24921064
TI  - Estimating causal effects in observational studies using Electronic Health Data:
      Challenges and (some) solutions.
AB  - Electronic health data sets, including electronic health records (EHR) and other
      administrative databases, are rich data sources that have the potential to help
      answer important questions about the effects of clinical interventions as well as
      policy changes. However, analyses using such data are almost always non
      experimental, leading to concerns that those who receive a particular
      intervention are likely different from those who do not, in ways that may
      confound the effects of interest. This paper outlines the challenges in
      estimating causal effects using electronic health data, and offers some
      solutions, with particular attention paid to propensity score methods that help
      ensure comparisons between similar groups. The methods are illustrated with a
      case study describing the design of a study using Medicare and Medicaid
      administrative data to estimate the effect of the Medicare Part D prescription
      drug program among individuals with serious mental illness.

PMID- 24921065
TI  - Methylerythritol 4-phosphate (MEP) pathway metabolic regulation.
AB  - Covering: up to February 2014. The methylerythritol 4-phosphate (MEP) pathway is
      the recently discovered source of isoprenoid precursors isopentenyl diphosphate
      (IDP) and dimethylallyl diphosphate (DMADP) in most bacteria, some eukaryotic
      parasites, and the plastids of plant cells. The precursors lead to the formation
      of various isoprenoids having diverse roles in different biological processes.
      Some isoprenoids have important commercial uses. Isoprene, which is made in
      surprising abundance by some trees, plays a significant role in atmospheric
      chemistry. The genetic regulation of this pathway has been discussed but
      information about metabolic regulation is just now becoming available. This
      review covers metabolic regulation of the MEP pathway starting from the inputs of
      carbon, ATP, and reducing power. A number of different regulatory mechanisms
      involving intermediate metabolites and/or enzymes are discussed. Some recent data
      indicate that methylerythritol cyclodiphosphate (MEcDP), the fifth intermediate
      of this pathway, is a key metabolite. It has been found to play diverse roles in
      regulation within the pathway as well as coordinating other biological processes
      by acting as a stress regulator in bacteria and possibly a retrograde signal from
      plastids to the nucleus in plants. In this review we focus on the role of the MEP
      pathway in photosynthetic leaves during isoprene emission and more generally the
      metabolic regulation of the MEP pathway in both plants and bacteria.

PMID- 24921066
TI  - 3 Tesla intraoperative MRI for brain tumor surgery.
AB  - Implementation of intraoperative magnetic resonance imaging (iMRI) has been shown
      to optimize the extent of resection and safety of brain tumor surgery. In
      addition, iMRI can help account for the phenomenon of brain shift and can help to
      detect complications earlier than routine postoperative imaging, which can
      potentially improve patient outcome. The higher signal-to-noise ratio offered by
      3 Tesla (T) iMRI compared with lower field strength systems is particularly
      advantageous. The purpose of this article is to review the imaging protocols,
      imaging findings, and technical considerations related to 3T iMRI. To maximize
      efficiency, iMRI sequences can be tailored to particular types of tumors and
      procedures, including nonenhancing brain tumor surgery, enhancing brain tumor
      surgery, transsphenoidal pituitary tumor surgery, and laser ablation. Unique
      imaging findings on iMRI include the presence of surgically induced enhancement,
      which can be a potential confounder for residual enhancing tumor, and hyperacute
      hemorrhage, which tends to have intermediate signal on T1-weighted sequences and
      high signal on T2-weighted sequences due to the presence of oxyhemoglobin. MR
      compatibility and radiofrequency shielding pose particularly stringent technical
      constraints at 3T and influence the design and usage of the surgical suite with
      iMRI.

PMID- 24921067
TI  - Actin expression in germinating seeds of Phaseolus vulgaris L.
AB  - Actin was present at very low levels in the seeds of common bean (Phaseolus
      vulgaris L.) compared with those from other species, and was observed mostly in
      the embryo. A time-course of actin expression in germinating bean seeds revealed
      an induced expression of both the mRNA and protein. Initially, the actin mRNA in
      seeds was barely detectable by northern blot analysis. However, there was a
      substantial increase in the expression of the actin mRNA at 24, 48 and 72 h after
      imbibition, compared with an internal control consisting of a late-embryogenesis
      abundant (LEA) type IV gene from P. vulgaris. An increase in the amount of actin
      in total seed extracts that parallelled that of the mRNA was detected by western
      blotting starting at 24 h after imbibition. This increase was more apparent when
      the embryo alone was analyzed. Two-dimensional west-ern blots initially revealed
      three actin isoforms with isoelectric points (pIs) of approximately 5.6, 5.7 and
      5.8,the amounts of which increased within a 48-h period,when a new minor isoform
      of pI approximately 5.5 appeared; however, after 72 h, the pI-5.8 isoform had
      almost disappeared and the pI-5.5 isoform had disappeared completely, indicating
      that these two minor isoforms are expressed transiently. These results indicate
      that actin is at very low levels in the dry seed but undergoes an increased and
      differential expression during imbibition, an event probably required to carry
      out all the necessary functions for germination.

PMID- 24921068
TI  - A systematic evaluation of protocols for a  proteomics analysis of (lyophilized)
      fruit  tissues.
AB  - This study represents a systematic evaluation of protocols for protein extraction
      and cleanup for fruit proteomic analysis. Procedures were optimized using pooled
      lyophilized banana fruit pulp, which is known to be particularly tricky due to
      high concentrations of soluble polysaccharides, phenolics, and other substances
      that interfere with protein extraction and purification. A total of 18
      combinations of three protein extraction procedures (SDS-based, Triton X-100
      based, and phenol-based), three protein precipitating agents (ammonium
      acetate/methanol, TCA/acetone, and acetone), and two resolubilization buffers
      (classical Rabilloud and the so-called R2D2) were compared for total protein
      yields and efficiency of recovery. The results demonstrate that while losses in
      total recovered protein are unavoidable, the degree of these losses depends on
      the method combinations used. Combinations based on buffer-saturated phenol
      always gave the highest yields, and overall recovery and purity was highest when
      acetone was combined with the R2D2 buffer for protein purification and
      concentration. Comparative 2D-PAGE analysis confirmed that this method
      combination produced high-quality and reproducible gels and the largest numbers
      of spots per gel. The usefulness of this methodology was demonstrated on ripe
      fruits from several other species and shown to give excellent results.

PMID- 24921069
TI  - [Young doctors: reconciling work and private life].

PMID- 24921070
TI  - A review of overgeneral memory in child psychopathology.
AB  - OBJECTIVES: Overgeneral autobiographical memory (OGM) refers to the impaired
      retrieval of specific events from autobiographical memory. This review examined
      OGM in children and adolescents to answer three main questions. First, do
      children demonstrate OGM? Second, how does the experience of OGM relate to
      childhood trauma and associated psychopathology? Third, is the CaR-FA-X model
      (Williams et al., 2007) able to explain OGM in child psychopathology once
      developmental issues have been considered? METHOD: Articles were identified in
      PsycINFO and PubMed searches using the terms overgeneral memory AND children,
      autobiographical memory specificity AND children, and autobiographical memory AND
      children. The authors reviewed 21 articles that examined OGM in young people aged
      7-18 years. Effect sizes were calculated for each study. RESULTS: The review
      demonstrated consistent support for a relationship with trauma exposure and
      depression symptoms in childhood. Furthermore, OGM was found to predict
      depression symptoms. Limited support was provided for the efficacy of the CaR-FA
      X model in young people. CONCLUSIONS: Future research will need to examine the
      influence of trauma characteristics on OGM development, along with the
      relationship of OGM to depression prognosis. Further investigation of the CaR-FA
      X model is required and developmental aspects will need to be taken into account.

PMID- 24921071
TI  - EIC editorial.

PMID- 24921072
TI  - Guest editorial: Computational solutions to large-scale data management and
      analysis in translational and personalized medicine.

PMID- 24921073
TI  - Communicating about opioids for chronic pain: a qualitative study of patient
      attributions and the influence of the patient-physician relationship.
AB  - BACKGROUND: Chronic pain poses numerous challenges for patients and providers,
      particularly when opioid treatment is discussed. Despite accounts of antagonistic
      patient-provider communication, little is known about how communication about
      opioids unfolds during clinic visits and, importantly, how the relationship
      history of a patient and physician shapes this communication. This study's
      objective was to advance understanding of communication about opioid treatment by
      recording primary care clinic visits and conducting in-depth interviews with
      patients to gain insight into the patient-provider relationship and its influence
      on clinical communication. METHOD: Forty patients with chronic pain were audio
      recorded during their primary care clinic appointments and then interviewed about
      their pain care and relationships with their providers. Ten patients were
      excluded from analysis because pain was not discussed during the clinic visit.
      RESULTS: Qualitative analysis revealed that patients responded in markedly
      different ways to similar physician treatment decisions about opioids. Some
      patients attributed limiting or denying opioids to physicians' distrust or lack
      of caring. Others attributed these limitations to acting out of genuine concern
      for patients' health. These attributions appeared to be shaped by features of the
      patient-physician relationship as described by patients. Results are discussed
      within the framework of attribution theory. CONCLUSIONS: Understanding how
      patients and providers discuss opioid treatment is critical for optimal pain
      treatment. Physicians might be able to improve communication by re-framing
      treatment discussions about opioids around external factors, such as benefits and
      harms, and engaging in communication that fosters a strong therapeutic alliance
      and emphasizes concern for the patient.

PMID- 24921074
TI  - Ecological momentary assessment for chronic pain in fibromyalgia using a
      smartphone: a randomized crossover study.
AB  - BACKGROUND: Daily diaries are a useful way of measuring fluctuations in pain
      related symptoms. However, traditional diaries do not assure the gathering of
      data in real time, not solving the problem of retrospective assessment.
      Ecological momentary assessment (EMA) by means of electronic diaries helps to
      improve repeated assessment. However, it is important to test its feasibility in
      specific populations in order to reach a wider number of people who could benefit
      from these procedures. METHODS: The present study compares the compliance and
      acceptability of an electronic diary running on a smartphone using a crossover
      design for a sample with a specific pain condition, fibromyalgia and low
      familiarity with technology. Forty-seven participants were randomly assigned to
      one of two conditions: (1) paper diary - smartphone diary and (2) smartphone
      diary - paper diary, using each assessment method for 1 week. RESULTS: The
      findings of this study showed that the smartphone diary made it possible to
      gather more accurate and complete ratings. Besides, this method was well accepted
      by a sample of patients with fibromyalgia referred by a public hospital, with an
      important proportion of participants with low level of education and low
      familiarity with technology. CONCLUSIONS: The findings of this study support the
      use of smartphones for EMA even in specific populations with a specific pain
      condition, fibromyalgia and with low familiarity with technology. These methods
      could help clinicians and researchers to gather more accurate ratings of relevant
      pain-related variables even in populations with low familiarity with technology.

PMID- 24921076
TI  - From right brain to left brain.

PMID- 24921077
TI  - A case of translational research: calcium transport in cardiomyocytes suggests
      novel approaches to treating arrhythmias.

PMID- 24921078
TI  - Carl Machover, 1927-2012.

PMID- 24921075
TI  - Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion.
AB  - Directed cell migration is critical for numerous physiological processes
      including development and wound healing. However chemotaxis is also exploited
      during cancer progression. Recent reports have suggested links between vesicle
      trafficking pathways and directed cell migration. Very little is known about the
      potential roles of endocytosis pathways during metastasis. Therefore we performed
      a series of studies employing a previously characterised model for chemotactic
      invasion of cancer cells to assess specific hypotheses potentially linking
      endocytosis to directed cell migration. Our results demonstrate that clathrin
      mediated endocytosis is indispensable for epidermal growth factor (EGF) directed
      chemotactic invasion of MDA-MB-231 cells. Conversely, caveolar endocytosis is not
      required in this mode of migration. We further found that chemoattractant
      receptor (EGFR) trafficking occurs by clathrin-mediated endocytosis and is
      polarised towards the front of migrating cells. However, we found no role for
      clathrin-mediated endocytosis in focal adhesion disassembly in this migration
      model. Thus, this study has characterised the role of endocytosis during
      chemotactic invasion and has identified functions mechanistically linking
      clathrin-mediated endocytosis to directed cell motility.

PMID- 24921079
TI  - Extreme-scale visual analytics.

PMID- 24921080
TI  - GAP-AF study helps to define optimal approach for atrial fibrillation ablation.

PMID- 24921081
TI  - Study of Ablation versus AntiaRrhythmic Drugs in Persistent Atrial Fibrillation
      study shows ablation superior to drugs for patients with persistent atrial
      fibrillation.

PMID- 24921082
TI  - Catheter ablation of atrial fibrillation as first-line treatment: is the future
      here now?

PMID- 24921084
TI  - A saturation of firsts: Lillian F. Schwartz.

PMID- 24921083
TI  - Use of clinical practice guidelines and factors related to their uptake: a survey
      of health professionals in Spain.
AB  - RATIONALE, AIMS AND OBJECTIVE: This study aims to assess the use of clinical
      practice guidelines (CPGs) among health professionals and factors related to
      their uptake in clinical practice. METHODS: Cross-sectional study based on an
      online survey conducted among primary care (PC) and hospital-based care (HC)
      doctors in Spain in 2011. Questionnaire development included adaptation of
      similar surveys and contextualization through a qualitative study. After a pilot
      study and review, the final survey contained five domains: demographics,
      involvement in CPGs, consultation of CPGs, perceptions and attitudes regarding
      CPGs and Spanish NHS CPGs Programme. Professionals from selected health care
      centres in seven regions were contacted by email with an invitation and link to
      the Web-based questionnaire. We analysed between-group differences and explored
      potential predictors of CPGs use by means of a logistic regression. RESULTS: Six
      hundred seventy-six doctors responded to the survey (27.7% response rate). 47.1%
      were PC and 49.5% were HC doctors. 32.5% stated previous involvement in CPGs and
      56.5% stated training in research methodology. 67.5% of the surveyed
      professionals reported using CPGs more than one time per week. The use of a
      system for classifying the quality of evidence (62.3%) and for grading the
      strength of the recommendations (58.6%), as well as the use of a rigorous
      methodology (49.6%), were the most frequently reported aspects related to CPG
      credibility. The lack of time (56.4%), especially in PC (65.3% versus 49.5% in
      HC; P < 0.001), and the absence of brief and easily accessible format (42.2%)
      were the main reported barriers to using CPGs. None of the studied factors showed
      statistically significant association in the logistic regression model.
      CONCLUSIONS: Study results suggest that, in general, Spanish doctors trust and
      use CPGs frequently. To improve uptake by health professionals and to overcome
      existing barriers, CPGs should be rigorously developed and made accessible at the
      point-of-care in user-friendly electronic formats. Due to the low response rate,
      findings should be extrapolated with caution.

PMID- 24921085
TI  - Biomedical applications: from data capture to modeling.

PMID- 24921086
TI  - Exceptionally long-term persistence of DNA adducts formed by  carcinogenic
      aristolochic acid I in renal tissue from patients  with aristolochic acid
      nephropathy.
AB  - Aristolochic acid (AA) causes aristolochic acid nephropathy (AAN), first
      described in women in Belgium accidently prescribed Aristolochia fangchi in a
      slimming treatment, and also Balkan endemic nephropathy (BEN), through probable
      dietary contamination with Aristolochia clematitis seeds. Both nephropathies have
      a high risk of urothelial cancer, with AA being the causative agent. In tissues
      of AAN and BEN patients, a distinct DNA adduct, 7-(deoxyadenosin-N6-yl)
      aristolactam I (dA-AAI), has been detected. DNA adducts can be removed through
      DNA repair, they can result in mutations through erroneous DNA replication or
      they can cause cell death. The dA-AAI adduct induces AT to TA transversions in
      the tumor-suppressor TP53 gene in experimental systems, matching TP53 mutations
      observed in urothelial tumors from AAN cancer cases. Using thin-layer
      chromatography 32P-postlabeling and mass spectrometric analysis we report the
      detection of dA-AAI in renal DNA from 11 Belgian AAN patients over 20 years after
      exposure to AA had ceased. Our results showed that dA-AAI is an established
      biomarker of AA exposure, and that this biomarker can be demonstrated to be
      persistent decades after a distinct AA exposure. Further, the persistence of dA
      AAI adducts appears to be a critical determinant for the AA mutational
      fingerprint frequently found in oncogenes and tumor suppressor genes recently
      identified by whole genome sequencing of AA-associated urothelial tumors. The
      potential for exposure to AA worldwide is high; the unprecedented long-term
      persistence of dA-AAI provides a useful long-term biomarker of exposure and
      attests to the role of AA in human urothelial malignancy.

PMID- 24921087
TI  - Improving the TNM classification: findings from a 10-year continuous literature
      review.
AB  - The Union for International Cancer Control's (UICC) TNM classification is a
      globally accepted system to describe the anatomic extent of malignant tumors.
      Since its development seventy years ago, the TNM classification has undergone
      significant revisions to reflect the current understanding of extent of disease
      and its role in prognosis. To ensure that revisions are evidence-based, the UICC
      implemented a process for continuous improvement of the TNM classification that
      included a formalized system for submitting proposals for revisions directly to
      the UICC and an annual review of the scientific literature on staging that
      assessed, criticized or made suggestions for changes. The process involves review
      of the proposals and literature by a group of international, multidisciplinary
      Expert Panels. The process has been in place for 10 years and informed the
      development of the 7th edition of the TNM classification published in 2009. The
      purpose of this article is to provide a description of the annual literature
      review process, including the search strategy, article selection process and the
      roles and requirements of the Expert Panels in the review of the literature.
      Since 2002, 147 Expert Panel members in 11 cancer sites have reviewed over 770
      articles. The results of the annual literature reviews, Expert Panel feedback and
      documentation and dissemination of results are described.

PMID- 24921088
TI  - Something out of nothing.

PMID- 24921090
TI  - Interactive public displays.

PMID- 24921089
TI  - Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles
      in adjacent lung tissue: Its correlation with smoking history and chronic
      obstructive pulmonary disease.
AB  - The aim of this study was to clarify the significance of DNA methylation
      alterations during lung carcinogenesis. Infinium assay was performed using 139
      paired samples of non-cancerous lung tissue (N) and tumorous tissue (T) from a
      learning cohort of patients with lung adenocarcinomas (LADCs). Fifty paired N and
      T samples from a validation cohort were also analyzed. DNA methylation
      alterations on 1,928 probes occurred in N samples relative to normal lung tissue
      from patients without primary lung tumors, and were inherited by, or strengthened
      in, T samples. Unsupervised hierarchical clustering using DNA methylation levels
      in N samples on all 26,447 probes subclustered patients into Cluster I (n = 32),
      Cluster II (n = 35) and Cluster III (n = 72). LADCs in Cluster I developed from
      the inflammatory background in chronic obstructive pulmonary disease (COPD) in
      heavy smokers and were locally invasive. Most patients in Cluster II were non
      smokers and had a favorable outcome. LADCs in Cluster III developed in light
      smokers were most aggressive (frequently showing lymphatic and blood vessel
      invasion, lymph node metastasis and an advanced pathological stage), and had a
      poor outcome. DNA methylation levels of hallmark genes for each cluster, such as
      IRX2, HOXD8, SPARCL1, RGS5 and EI24, were again correlated with
      clinicopathological characteristics in the validation cohort. DNA methylation
      profiles reflecting carcinogenetic factors such as smoking and COPD appear to be
      established in non-cancerous lung tissue from patients with LADCs and may
      determine the aggressiveness of tumors developing in individual patients, and
      thus patient outcome.

PMID- 24921092
TI  - Shrinking hardware, expanding interfaces.

PMID- 24921091
TI  - PhotoCloud: Interactive remote exploration of joint 2D and 3D datasets.
AB  - PhotoCloud is a real-time client-server system for interactive visualization and
      exploration of large datasets comprising thousands of calibrated 2D photographs
      of a scene and a complex 3D description of the scene. The system isn't tailored
      to any specific data acquisition process; it aims at generality and flexibility.
      PhotoCloud achieves scalability through a multiresolution dynamic hierarchical
      representation of the data, which is remotely stored and accessed by the client
      through an efficient cache system. The system includes a compact image browser
      and a multiresolution model renderer. PhotoCloud employs iconic visualization of
      the images in the 3D space and projects images onto the 3D scene on the fly.
      Users can navigate the 2D and 3D spaces with smooth, integrated, seamless
      transitions between them. A study with differently skilled users confirms
      PhotoCloud's effectiveness and communication power. The Web extras at
      http://www.youtube.com/playlist?list=PLHJB2bhmgB7cmYD0ST9CEDMRv1JlX4xPH are
      videos demonstrating PhotoCloud, a real-time client-server system for interactive
      exploration of large datasets comprising 2D photos and 3D models.

PMID- 24921093
TI  - Creation and deconstruction.
AB  - This issue's article examines the digital artwork of Edwin van Munster.

PMID- 24921094
TI  - Scattering: acquisition, modeling, and rendering.

PMID- 24921095
TI  - Big-data visualization.

PMID- 24921096
TI  - Computational aspects of fabrication modeling, design, and 3D printing.

PMID- 24921097
TI  - Dreams, tea, and science.

PMID- 24921098
TI  - 2012 IEEE Visualization Contest winner: Visualizing polarization domains in
      barium titanate.

PMID- 24921099
TI  - 3D for the Web.

PMID- 24921100
TI  - The need to start research education early.

PMID- 24921102
TI  - Marie T. Filbin: in memoriam.

PMID- 24921103
TI  - Historians and their sources.

PMID- 24921104
TI  - John Ray in Italy: lost manuscripts rediscovered.
AB  - This paper discloses the content of two manuscripts of John Ray that have
      hitherto been unknown to Ray scholars. The manuscripts survive in the Hampshire
      Record Office, having descended through the Prideaux-Brune family. They record
      information about Ray's tour of Italy in the 1660s that does not appear in his
      Observations... made in a journey through... the Low-countries, Germany, Italy
      and France (1673), including a visit to the museum of Athanasius Kircher in Rome,
      and provide clues concerning the composition of Ray's 1673 book.

PMID- 24921105
TI  - The scholar as craftsman: Derek de Solla Price and the reconstruction of a
      medieval instrument.
AB  - The Royal Society Conversaziones were biannual social evenings at which
      distinguished guests could learn about the latest scientific developments. The
      Conversazione in May 1952 featured an object that came to be called King Arthur's
      Table. It was a planetary equatorium, made in Cambridge's Cavendish Laboratory at
      the behest of Sir Lawrence Bragg. Conceived by the historian of science Derek de
      Solla Price as a huge, tangible realization of Chaucerian astronomy, it was
      displayed at the new Whipple Museum of the History of Science, discarded, stored
      incognito, catalogued with that whimsical name, and finally re-identified in
      2012. This article examines the biography of that object and, through it, the
      early, inchoate years of the discipline of history of science in Cambridge. The
      process of disciplinary establishment involved a range of actors beyond well
      known figures such as Herbert Butterfield and Joseph Needham; the roles of Price
      and Bragg are highlighted here. Study of these individuals, and of the
      collaboration that brought about the reconstruction, reveals much about the
      establishment of a discipline, as well as changing scholarly and curatorial
      attitudes towards replicas.

PMID- 24921106
TI  - Observing the skies of Lisbon. Isaac de Sequeira Samuda, an estrangeirado in the
      Royal Society.
AB  - Elected in 1723, Isaac de Sequeira Samuda (1681-1729) was the first Jewish Fellow
      of the Royal Society. He had arrived in London just a few years earlier, escaping
      from the Portuguese Inquisition. Despite his past, he had no difficulty in
      establishing links with his country's diplomatic representatives in London. A
      physician and adviser on scientific subjects, he became a conduit between the
      emerging world of Portuguese astronomy and the British scientific community. He
      reported to the Royal Society on astronomical observations made in the new
      observatories in Lisbon and helped with the acquisition of scientific instruments
      and books destined for Portugal. These activities were facets of Samuda's unusual
      career and the diverse though often converging associations that he established
      until his death. As the member of a network active in the diffusion of new ideas
      and in the modernization of Portuguese science, Samuda can be regarded as an
      estrangeirado, as this term has come to be used in the modern literature.

PMID- 24921108
TI  - Wallace, Darwin and Ternate 1858.
AB  - Recent debates on the mailing date of Alfred Russel Wallace's 'Ternate essay' to
      Charles Darwin in the spring of 1858 have ignored certain details that, once
      taken into account, alter the matter considerably. Here, a closer look is taken
      at the critical question of whether Wallace's manuscript-accompanying letter
      represented a reply to the Darwin letter that arrived in Ternate on 9 March; it
      is concluded that it very probably did not.

PMID- 24921107
TI  - John Tyndall and the Royal Medal that was never struck.
AB  - Just once in its long history has a Royal Medal been awarded but not presented.
      John Tyndall FRS (1820-93) was the chosen recipient in 1853 for his early work on
      diamagnetism but declined to accept it. The story of why Tyndall felt compelled
      to turn down this considerable honour sheds light on the scientific politics and
      personal relationships of the time, on the importance given to the study of
      magnetism, and on Tyndall's own character and career.

PMID- 24921109
TI  - Lord Justice of Appeal John Fletcher Moulton and explosives production in World
      War I: 'the mathematical mind triumphant'.
AB  - At the end of November 1914 Lord Moulton (1844-1921) became the director of
      explosives production in the War Office. A 70-year-old jurist may seem an
      extraordinary choice, but he was an extraordinary man. He was Senior Wrangler at
      Cambridge, was elected to the Royal Society for research on electricity, and
      learned about chemistry as a barrister for dye and explosives manufacturers. He
      assembled an able team of administrators and chemists who designed and managed
      mammoth new national explosives factories. They could not make enough TNT and
      picric acid from obtainable precursors, so Moulton persuaded the reluctant armed
      services to adopt mixtures of TNT and ammonium nitrate, which enabled them to
      make even more than was needed. In mid-1915 they moved to the new Ministry of
      Munitions, where they also became responsible for fertilizers and poison gases.
      In 1917 they produced explosives at a higher rate than was attained in World War
      II.

PMID- 24921110
TI  - An attenuated philosophical gentleman.
AB  - Dr. Joseph Black had at one time, a house near us to the west. He was a striking
      and beautiful person; tall, very thin, and cadaverously pale; his hair carefully
      powdered, though there was little of it except what was collected in a long thin
      queue; his eyes dark, clear and large, like deep pools of pure water. He wore
      black speckless clothes, silk stockings, silver buckles, and either a slim green
      umbrella, or a genteel brown cane. The general frame and air were feeble and
      slender. The wildest boy respected Black. No lad could be irreverent toward a man
      so pale, so gentle, so elegant and so illustrious. So he glided, like a spirit,
      through our rather mischievous sportiveness, unharmed. He died seated, with a
      bowl of milk upon his knee, of which his ceasing to be did not spill a drop; a
      departure which it seemed, after the event, might have been foretold of this
      attenuated philosophical gentleman.

PMID- 24921119
TI  - Design of a GaP/Si composite waveguide for CW terahertz wave generation via
      difference frequency mixing.
AB  - We design a GaP/Si composite waveguide to achieve efficient terahertz (THz) wave
      generation under collinear phase-matched difference frequency mixing (DFM)
      between near-infrared light sources. This waveguide structure provides a strong
      mode confinement of both near-infrared sources and THz wave, resulting in an
      efficient mode overlapping. The numerical results show that the waveguide can
      produce guided THz wave (5.93 THz) with a power conversion efficiency of 6.6*10(
      4)  W(-1). This value is larger than previously obtained with the bulk GaP
      crystal: 0.5*10(-9)  W(-1) [J. Lightwave Technol.27, 3057 (2009)]. Our proposed
      composite waveguide can be achieved by bridging the telecom wavelength and THz
      frequency region.

PMID- 24921120
TI  - Interferometric investigation of the influence of argon buffer gas on the
      characteristics of laser-induced aluminum plasmas.
AB  - An interferometric analysis was performed to investigate the influence of argon
      (Ar) buffer gas on the characteristics of laser-induced aluminum (Al) plasma at
      atmospheric pressure. The plasma was produced by focusing a Q-switched Nd:YAG
      laser pulse (lambda=1064  nm, pulse duration ~5  ns, E=6.0  mJ) onto an Al
      target. The interference patterns were constructed using a Nomarski
      interferometer incorporated with a frequency-doubled, Q-switched Nd:YAG laser
      (lambda=532  nm, pulse duration ~10  ns) that generates an interferometric probe
      beam. The interferometric measurements were carried out as a function of the
      elapsed time after the onset of breakdown under the conditions of open air and an
      Ar gas jet flow (5  l/min). With the injection of an Ar buffer gas jet in the
      ablation process, an increase in electron density and a preferential axial plasma
      expansion of the plasma plume were observed during the early stages of plasma
      formation as a consequence of increased inverse-Bremsstrahlung (IB) absorption
      efficiency.

PMID- 24921121
TI  - Comparisons of three NILU-UV instruments deployed at the same site in the New
      York area.
AB  - The Norwegian Institute for Air Research ultraviolet (NILU-UV) irradiance meter
      is a ground-based, multichannel, moderate bandwidth filter instrument that
      measures irradiances at ultraviolet (UV) and visible wavelengths with five
      channels in the UV (302, 312, 320, 340, and 380 nm) and one channel in the
      visible (400-700 nm) part of the spectrum. Minute-by-minute irradiances recorded
      in these channels are used to infer the total ozone column (TOC) amount, and a
      radiation modification factor (RMF) designed to have a value close to 100 under
      cloud-free conditions. The performance of three NILU-UV instruments deployed side
      by-side in the New York area (40.74 degrees N, -74.03 degrees E) is assessed, and
      derived TOC values are compared with those derived from the ozone monitoring
      instrument (OMI) deployed on NASA's AURA satellite. Based on about three years of
      data, it was found that the three instruments yielded similar TOC values that
      were in close agreement with those derived from the OMI. The relative difference
      in TOC values derived from the three NILU-UV instruments was generally less than
      2.5%. Cloud cover affects the accuracy of the inferred TOC, but reliable values
      can be obtained in the presence of clouds, although the accuracy deteriorates
      under heavy overcast conditions with RMF values smaller than 65 (low cloud
      transmittance).

PMID- 24921122
TI  - Random wandering of laser beams with orbital angular momentum during propagation
      through atmospheric turbulence.
AB  - The propagation of laser beams having orbital angular momenta (OAM) in the
      turbulent atmosphere is studied numerically. The variance of random wandering of
      these beams is investigated with the use of the Monte Carlo technique. It is
      found that, among various types of vortex laser beams, such as the Laguerre
      Gaussian (LG) beam, modified Bessel-Gaussian beam, and hypergeometric Gaussian
      beam, having identical initial effective radii and OAM, the LG beam occupying the
      largest effective volume in space is the most stable one. 

PMID- 24921123
TI  - Aluminum-thin-film packaged fiber Bragg grating probes for monitoring the maximum
      tensile strain of composite materials.
AB  - In this paper, new fiber Bragg grating (FBG) sensor probes are designed to
      intermittently detect the maximum tensile strain of composite materials, so as to
      evaluate the structural health status. This probe is fabricated by two thin Al
      films bonded to an FBG optical fiber and two supporting brackets, which are fixed
      on the surface of composite materials. The residual strain of the Al packaged FBG
      sensor probe is induced by the strain of composite materials. This residual
      strain can indicate the maximum strain of composite materials. Two types of
      sensor probes are prepared-one is an FBG with 18 MUm thick Al films, and the
      other is an FBG with 36 MUm thick Al films-to compare the thickness effect on the
      detection sensitivity. These sensor probes are bonded on the surfaces of carbon
      fiber reinforced plastics composite specimens. In order to determine the strain
      sensitivity between the residual strain of the FBG sensor probe and the maximum
      strain of the composite specimen, tensile tests are performed by universal
      testing machine, under the loading-unloading test condition. The strain
      sensitivities of the probes, which have the Al thicknesses of 18 and 36 MUm, are
      determined as 0.13 and 0.23, respectively.

PMID- 24921124
TI  - Beyond the interference problem: hierarchical patterns for multiple-projector
      structured light system.
AB  - Three-dimensional reconstruction of a dynamic object based on the structured
      light (SL) technique has attracted intensive research. Since a single projector
      only covers a limited area of the scene, multiple projectors should be employed
      simultaneously to extend the imaging area for a 3D object. However, patterns
      projected by different projectors superpose each other in a light-intersected
      area, which makes it difficult to recognize the original patterns and obtain the
      correct depth maps. To solve such a problem, we propose a method to design
      hierarchical patterns that can be separated from each other. In the proposed
      patterns, each pixel in binary patterns based on the de Bruijn sequence is
      replaced by a different bin with limited size. Then the proposed patterns can be
      separated by identifying distributions of colors in each bin in superposed
      patterns, and depth maps are obtained by decoding the separated patterns. To
      verify the performance of the proposed method, we design two hierarchical
      patterns and conduct several experiments in different scenes. Experimental
      results demonstrate that the proposed patterns can be separated in a multiple
      projector SL system to obtain accurate depth maps, and they are robust for
      different conditions. 

PMID- 24921125
TI  - Optically isotropic switchable microlens arrays based on liquid crystal.
AB  - We present an optically isotropic switchable microlens array (MLA) based on
      liquid crystals (LCs) using the Joule heating electrode structure. The LC
      molecules were initially aligned vertically on the lens and electrode surfaces.
      By applying voltage to the transparent electrodes, the temperature of the LC
      layer could be changed. Above the clearing point temperature of LCs, the LC layer
      shows an averaged refractive index that differs from the nematic state refractive
      index. The MLA could have switching characteristics by index matching between the
      LC layer and polymer lens structure. The proposed switchable MLA shows high light
      efficiency with truly optically isotropic properties. 

PMID- 24921126
TI  - Influence of Al fraction on photoemission performance of AlGaN photocathode.
AB  - To research the photoemission performance of a transmission-mode Al(1-x)Ga(x)N
      photocathode, Al0.24Ga0.76N and GaN photocathodes with the same structure were
      activated, their spectral responses were measured using a multi-information
      measurement system at room temperature, and the photocathode parameters were
      obtained by fitting quantum efficiency curves. The results showed that both the
      reflective-mode and transmission-mode spectral responses of the AlGaN
      photocathode were lower than those of the GaN photocathode. Compared with the GaN
      photocathode, the short-wavelength spectral response of the Al0.24Ga0.76N
      photocathode was less seriously affected by lattice defects between the buffer
      and emission layers. The Al atom at the AlGaN photocathode surface could affect
      the optimal Cs adsorption position, which mainly affects the surface electron
      escape probability of the photocathode.

PMID- 24921127
TI  - Significantly increased surface plasmon polariton mode excitation using a
      multilayer insulation structure in a metal-insulator-metal plasmonic waveguide.
AB  - In this paper, we propose a novel multilayer insulation structure in a metal
      insulator-metal (MIM) plasmonic waveguide to explore the possibility of
      increasing surface plasmon polariton (SPP) mode excitation. Numerical
      investigations show that the effective refractive index of the multilayer
      insulation structure affects symmetric SPP mode excitation. The significant
      enhancement of electric field intensity in horizontal and vertical profiles with
      a dipole in SiO2 compared with in Al2O3 is observed in the proposed MIM plasmonic
      waveguides due to a combination of the improved optical density and dipole
      radiation intensities under a low refractive index. The Au/SiO2/Al2O3/SiO2/Au
      geometry shows the best enhancement performances, which can serve as an excellent
      guideline for designing and optimizing a high-performance SPP source using a
      multilayer insulation structure.

PMID- 24921128
TI  - Retroreflective imaging system for optical labeling and detection of
      microorganisms.
AB  - A retroreflective imaging system for imaging microscopic targets over macroscopic
      sampling areas is introduced. Detection of microorganism-bound retroreflector
      (RR) targets across millimeter-scale samples is implemented according to
      retroreflection directionality, collimation, and contrast design characteristics.
      Retroreflection directionality is considered for corner-cube (CC) and spherical
      geometries. Spherical-RRs improve directionality and reliability. Retroreflection
      collimation is considered for spherical-RRs. Retroreflective images for micro-CC
      RRs and micro-spherical-RRs with varying refractive indices show optimal results
      for high refractive index BaTiO3 micro-spherical-RRs. A differential imaging
      technique improves retroreflection contrast by 35 dB. High refractive index micro
      spherical-RRs and differential imaging, together, can detect microscopic RR
      targets across macroscopic areas.

PMID- 24921129
TI  - Polarization-independent light-dispersing optical device consisting of two
      diffraction gratings and a waveplate.
AB  - We report on a light-dispersing device consisting of two transmission gratings
      and a waveplate. The gratings separate two orthogonal polarization components of
      light incident at the Bragg angle. The waveplate, which is sandwiched between the
      gratings, functions as a polarization converter for oblique light incidence. With
      these optical parts suitably integrated, the resulting device efficiently
      diffracts unpolarized light with high spectral resolution. Using coupled-wave
      theories and Mueller matrix analysis, we constructed a device for a wavelength
      range of 680+/-50  nm with a 400 nm grating period. From the characterization of
      this optical device, we validated the proposed polarization-independent, light
      dispersing concept.

PMID- 24921130
TI  - Real-time compensation of phase distortions by digital phase conjugation using
      CCD and liquid crystal panel.
AB  - A video-rate optical phase conjugator using an image sensor and a liquid crystal
      panel that operated at 30 Hz was developed and its temporal characteristic was
      studied. Strong air turbulence of atmospheric structure constant, Cn=6.3*10(-7) 
      [m(-1/3)], was successfully compensated, reducing beam dancing by a factor of 2.
      To our knowledge, this is the first report demonstrating real-time wavefront
      correction by digital phase conjugation using commercial devices.

PMID- 24921131
TI  - Photonic-crystal fiber-based pressure sensor for dual environment monitoring.
AB  - In this paper the development of a side-hole photonic-crystal fiber (SH-PCF)
      pressure sensor for dual environment monitoring is reported. SH-PCF properties
      (phase and group birefringence, sensitivity to pressure variations) are measured
      and compared to simulated data. In order to probe two environments, two sections
      of the SH-PCF with different lengths are spliced and set in a Solc filter-like
      configuration. This setup allows obtaining the individual responses of the first
      and second fiber independently, which is useful for a space-multiplexed
      measurement. As the employed fiber is sensitive to pressure variations, we report
      the use of this configuration for dual environment pressure sensing. 

PMID- 24921132
TI  - Antireflection efficiency comparison of single- and double-layered structures for
      photovoltaic glass covers.
AB  - For single-layer antireflection (AR) on glass, a low refractive index (n) AR
      layer is required to achieve high AR efficiency, which limits the selection of
      materials. The double-layered AR structure has a lower requirement on materials'
      n but is typically used for narrow waveband AR, and photovoltaic glass covers
      require broadband AR to increase the whole-spectrum solar energy transmittance.
      With the help of a multilayered optical simulation, we optimized the n and
      thickness of the single and double layered AR structure and found that, for
      broadband AR, double-layered structure only showed AR efficiency advantages in
      very high or low top layers' n compared to single AR layer structure. For a
      n=1.45 top layer of the double layer structure, the optimized reflectance is
      2.57% (single side), while the optimized reflectance of a single AR layer with
      n=1.45 is 2.87%, which is a negligible AR efficiency advantage (0.30%) when
      considering production costs. Moreover, in our experiment, using SiO2 and SiO2
      and TiO2 composite layers, the absorption of short wavelengths by TiO2 ostensibly
      cancelled this advantage out (92.87% compare to the single layer's 92.98% for
      single side AR).

PMID- 24921133
TI  - Simple fabrication of liquid crystalline grating cells with homogeneous and
      twisted nematic structures and effects of orientational relaxation on diffraction
      properties.
AB  - We have substantiated a simple yet efficient, competitive, and practical method
      to automatically fabricate liquid crystalline grating cells with homogeneous or
      twisted nematic (TN) structures by one-step ultraviolet holographic exposure on
      an empty glass cell coated with a photocrosslinkable polymer liquid crystal with
      4-(4-methoxycinnamoyloxy)biphenyl side group (P6CB) films. The polarization
      diffraction properties in the resultant liquid crystalline grating cells have
      also been investigated extensively by varying the grating pitch. The theoretical
      considerations on the basis of elastic continuum theory revealed that
      accumulation of elastic free-energy density due to the TN structure affected the
      diffraction properties, although the strong anchoring of our photoalignment
      material contributed effectively to form the expected spatial distribution of
      liquid crystalline directors in the grating cells. 

PMID- 24921134
TI  - Microwave photonic mixer with high spurious-free dynamic range.
AB  - A new linearized photonic mixer structure, which can fully eliminate the third
      order intermodulation distortion, is presented. It is based on an integrated dual
      parallel Mach-Zehnder modulator to which an optimized RF split and an optimized
      optical phase shift are applied, in series with a Mach-Zehnder modulator driven
      by the LO. The mixer achieves a very high spurious-free dynamic range
      performance, it enables essentially infinite isolation between the RF and LO
      ports, and it has the ability to function over a multioctave frequency range.
      Experimental results demonstrate a record measured spurious free dynamic range
      performance of 127 dB.Hz(4/5), which is over 22 dB higher than that of the
      conventional dual-series Mach-Zehnder modulator-based microwave photonic mixer.

PMID- 24921135
TI  - Wide-angle camera with multichannel architecture using microlenses on a curved
      surface.
AB  - We propose a multichannel imaging system that combines the principles of an
      insect's compound eye and the human eye. The optical system enables a reduction
      in track length of the imaging device to achieve miniaturization. The
      multichannel structure is achieved by a curved microlens array, and a Hypergon
      lens is used as the main lens to simulate the human eye, achieving large field of
      view (FOV). With this architecture, each microlens of the array transmits a
      segment of the overall FOV. The partial images are recorded in separate channels
      and stitched together to form the final image of the whole FOV by image
      processing. The design is 2.7 mm thick, with 59 channels; the 100 degrees *80
      degrees  full FOV is optimized using ZEMAX ray-tracing software on an image
      plane. The image plane size is 4.53  mm*3.29  mm. Given the recent progress in
      the fabrication of microlenses, this image system has the potential to be
      commercialized in the near future.

PMID- 24921136
TI  - Generation of azimuthally polarized beams in fast axial flow CO2 laser with
      hybrid circular subwavelength grating mirror.
AB  - A hybrid circular subwavelength grating mirror is proposed and fabricated as a
      rear mirror in a fast axial flow CO2 laser system to generate azimuthally
      polarized beams (APBs). This grating mirror, with particular gold-covered ridges
      and nanopillar-stuffed grooves, performs wideband TE wave reflectivity and high
      polarization selectivity. It shows that the polarization selectivity mechanism
      lies in the gold ridge's high reflectivity to the TE wave and the lower TM wave
      reflectivity, which are the result of the mode leaking into substrate through the
      dielectric-like nanopillar layer. Finally, a high-quality 550 W APB is obtained
      in subsequent experiments, which provides potential applications in drilling and
      welding.

PMID- 24921137
TI  - Inverse solutions for tilting orthogonal double prisms.
AB  - An analytical reverse solution and actual examples are given to show how to
      direct a laser beam from a pair of orthogonal prisms to given targets in free
      space. Considering the influences of double-prism structural parameters, a lookup
      table method to seek the numerical reverse solution of each prism's tilting angle
      is also proposed for steering the double-prism orientation to track a target
      position located in the near field. Some case studies, as well as a specified
      elliptical target trajectory scanned by the cam-based driving double prisms,
      exhibit the significant application values of the theoretical derivation. The
      analytic reverse and numerical solutions can be generalized to investigate the
      synthesis of scanning patterns and the controlling strategy of double-prism
      tilting motion, the potentials of which can be explored to perform the
      orientation and position tracking functions in applications of precision
      engineering fields. 

PMID- 24921138
TI  - Solving self-mixing equations for arbitrary feedback levels: a concise algorithm.
AB  - Self-mixing laser sensors show promise for a wide range of sensing applications,
      including displacement, velocimetry, and fluid flow measurements. Several
      techniques have been developed to simulate self-mixing signals; however, a
      complete and succinct process for synthesizing self-mixing signals has so far
      been absent in the open literature. This article provides a systematic numerical
      approach for the analysis of self-mixing sensors using the steady-state solution
      to the Lang and Kobayashi model. Examples are given to show how this method can
      be used to synthesize self-mixing signals for arbitrary feedback levels and for
      displacement, distance, and velocity measurement. We examine these applications
      with a deterministic stimulus and discuss the velocity measurement of a rough
      surface, which necessitates the inclusion of a random stimulus. 

PMID- 24921139
TI  - Algebraic solution for phase unwrapping problems in multiwavelength
      interferometry.
AB  - Recent advances in multiwavelength interferometry techniques [Appl. Opt.52, 5758
      (2013)] give new insights to phase unwrapping problems and allow the fringe order
      information contained in the measured phase to be extracted with low
      computational effort. This work introduces an algebraic solution to the phase
      unwrapping problem that allows the direct calculation of the unknown integer
      fringe order. The procedure resembles beat-wavelength approaches, but provides
      greater flexibility in choosing the measurement wavelengths, a larger measurement
      range, and a higher robustness against noise, due to the ability to correct for
      errors during the calculation. 

PMID- 24921140
TI  - Measuring refractive index using the focal displacement method.
AB  - A simple technique is introduced for measuring the refractive index of plane
      parallel samples having thickness of the order of a millimeter. The refractive
      index values are reported for six bulk semiconductors, each index measured at two
      infrared wavelengths using this method. The values are found to be within a few
      percent of those in literature for four semiconductors. The other two
      semiconductors were newly grown ternary alloys (CdMgTe and CdMnTe), for which the
      refractive index values have not been reported previously at the wavelengths
      studied here. 

PMID- 24921141
TI  - Multi-element double ring detector for dual band infrared counter-countermeasure.
AB  - A multi-element double ring detector which can track a target effectively under
      infrared (IR) countermeasure conditions is presented. Dual band IR counter
      countermeasures can be performed by the detector to distinguish the target from
      target-flare mixed signals. Middle and short IR wavelengths are used for target
      and IR countermeasure detection, respectively. With a special design, unique dual
      band signals will be outputted by the detector when a target spot is located on
      the center of the detector. By comparison, the typical single element ring
      detector has a "dead spot" in this case, which is undesirable for target
      identification. Relatively high tracking accuracy and low cost indicate that the
      presented method has a potential application. 

PMID- 24921142
TI  - Bit error rate analysis of Gaussian, annular Gaussian, cos Gaussian, and cosh
      Gaussian beams with the help of random phase screens.
AB  - Using the random phase screen approach, we carry out a simulation analysis of the
      probability of error performance of Gaussian, annular Gaussian, cos Gaussian, and
      cosh Gaussian beams. In our scenario, these beams are intensity-modulated by the
      randomly generated binary symbols of an electrical message signal and then
      launched from the transmitter plane in equal powers. They propagate through a
      turbulent atmosphere modeled by a series of random phase screens. Upon arriving
      at the receiver plane, detection is performed in a circuitry consisting of a pin
      photodiode and a matched filter. The symbols detected are compared with the
      transmitted ones, errors are counted, and from there the probability of error is
      evaluated numerically. Within the range of source and propagation parameters
      tested, the lowest probability of error is obtained for the annular Gaussian
      beam. Our investigation reveals that there is hardly any difference between the
      aperture-averaged scintillations of the beams used, and the distinctive advantage
      of the annular Gaussian beam lies in the fact that the receiver aperture captures
      the maximum amount of power when this particular beam is launched from the
      transmitter plane. 

PMID- 24921143
TI  - Nonrigid registration with free-form deformation model of multilevel uniform
      cubic B-splines: application to image registration and distortion correction of
      spectral image cubes.
AB  - In spectral imaging, spatial and spectral information of an image scene are
      combined. There exist several technologies that allow the acquisition of this
      kind of data. Depending on the optical components used in the spectral imaging
      systems, misalignment between image channels can occur. Further, the projection
      of some systems deviates from that of a perfect optical lens system enough that a
      distortion of scene content in the images becomes apparent to the observer.
      Correcting distortion and misalignment can be complicated for spectral image data
      if they are different at each image channel. In this work, we propose an image
      registration and distortion correction scheme for spectral image cubes that is
      based on a free-form deformation model of uniform cubic B-splines with multilevel
      grid refinement. This scheme is adaptive with respect to image size, degree of
      misalignment, and degree of distortion, and in that sense is superior to previous
      approaches. We support our proposed scheme with empirical data from a Bragg
      grating-based hyperspectral imager, for which a registration accuracy of
      approximately one pixel was achieved. 

PMID- 24921144
TI  - Design of high-resolution and multilevel reference pattern for improvement of
      both light utilization efficiency and signal-to-noise ratio in coaxial
      holographic data storage.
AB  - A high-resolution and multilevel designed reference pattern (DRP) is presented
      for improvement of both light utilization efficiency and the signal-to-noise
      ratio (SNR) of reconstructed images in coaxial holographic data storage. With a
      DRP, the desired Fourier power spectrum of a reference beam is obtained.
      Numerical and experimental results show that the DRP increases the SNR compared
      with that of a random phase mask (RPM). Moreover, the light utilization
      efficiency of the DRP is higher than that of a high-resolution RPM. In addition,
      the effect of the phase level and the pixel pitch of DRPs on the SNR and the
      light utilization efficiency are investigated. 

PMID- 24921145
TI  - Axial intensity distribution analysis for a depth-of-field-extended optical
      system using a low-frequency binary phase mask.
AB  - This paper theoretically analyzes the axial intensity distribution of an optical
      imaging system with a low-frequency binary phase mask. Based on the derivation, a
      novel but simple one-step phase mask is designed to extend the depth of field. A
      comparison is made between the novel phase mask and the one designed in previous
      research [Opt. Express14, 2631 (2006)]. Both masks are numerically tested in an
      achromatic doublet system. The numerical results show that two phase masks have
      comparable performance in depth of field extension. However, the phase mask
      designed in this paper has a simpler structure because it has only one step while
      the previous one has two. Consequently, the easy fabrication of the novel phase
      mask leads to cost reduction. This novel low-frequency binary phase mask provides
      a new choice to design depth-of-field-extended optical systems without digital
      image processing. 

PMID- 24921146
TI  - Enhanced performance configuration for fast-switching deformed helix
      ferroelectric liquid crystal continuous tunable Lyot filter.
AB  - In this paper, we present a novel design configuration of double DHFLC wave plate
      continuous tunable Lyot filter, which exhibits a rapid response time of 185 MUs,
      while the high-contrast ratio between the passband and stop band is maintained
      throughout a wide tunable range. A DHFLC tunable filter with a high-contrast
      ratio is attractive for realizing high-speed optical processing devices, such as
      multispectral and hyperspectral imaging systems, real-time remote sensing, field
      sequential color display, and wavelength demultiplexing in the metro network. In
      this work, an experimental prototype for a single-stage DHFLC Lyot filter of this
      design has been fabricated using photoalignment technology. We have demonstrated
      that the filter has a continuous tunable range of 30 nm for a blue wavelength, 45
      nm for a green wavelength, and more than 50 nm for a red wavelength when the
      applied voltage gradually increases from 0 to 8 V. Within this tunable range, the
      contrast ratio of the proposed double wave plate configuration is maintained
      above 20 with small deviation in the transmittance level. Simulation and
      experimental results showed the proposed double DHFLC wave plate configuration
      enhances the contrast ratio of the tunable filter and, thus, increases the
      tunable range of the filter when compared with the Lyot filter using a single
      DHFLC wave plate. Moreover, we have proposed a polarization insensitive
      configuration for which the efficiency of the existing prototype can
      theoretically be doubled by the use of polarization beam splitters.

PMID- 24921147
TI  - Mitigation of beam fluctuation due to atmospheric turbulence and prediction of
      control quality using intelligent decision-making tools.
AB  - In free-space optical link (FSOL), atmospheric turbulence causes fluctuations in
      both intensity and phase of the received beam and impairing link performance. The
      beam motion is one of the main causes for major power loss. This paper presents
      an investigation on the performance of two types of controller designed for
      aiming a laser beam to be at a particular spot under dynamic disturbances. The
      multiple experiment observability nonlinear input-output data mapping is used as
      the principal components for controllers design. The first design is based on the
      Taguchi method while the second is artificial neural network method. These
      controllers process the beam location information from a static linear map of 2D
      plane: optoelectronic position detector, as observer, and then generate the
      necessary outputs to steer the beam with a microelectromechanical mirror: fast
      steering mirror. The beam centroid is computed using monopulse algorithm.
      Evidence of suitability and effectiveness of the proposed controllers are
      comprehensively assessed and quantitatively measured in terms of coefficient of
      correlation, correction speed, control exactness, centroid displacement, and
      stability of the receiver signal through the experimental results from the FSO
      link setup established for the horizontal range of 0.5 km at an altitude of 15.25
      m. The test field type is open flat terrain, grass, and few isolated obstacles. 

PMID- 24921148
TI  - All-optical XNOR/NOT logic gates and LATCH based on a reflective vertical cavity
      semiconductor saturable absorber.
AB  - This work proposes a scheme of all-optical XNOR/NOT logic gates based on a
      reflective vertical cavity semiconductor (quantum wells, QWs) saturable absorber
      (VCSSA). In a semiconductor Fabry-Perot cavity operated with a low-intensity
      resonance wavelength, both intensity-dependent saturating phase-shift and thermal
      phase-shift occur, which are considered in the proposed logic operations. The
      VCSSA-based logics are possible using the saturable behavior of reflectivity
      under the typical operating conditions. The low-intensity saturable reflectivity
      is reported for all-optical logic operations where all possible nonlinear phase
      shifts are ignored. Here, saturable absorption (SA) and the nonlinear phase-shift
      based all-optical XNOR/NOT gates and one-bit memory or LATCH are proposed under
      new operating conditions. All operations are demonstrated for a VCSSA based on
      InGaAs/InP QWs. These types of SA-based logic devices can be comfortably used for
      a signal bit rate of about 10 GHz corresponding to the carrier recovery time of
      the semiconductor material. 

PMID- 24921149
TI  - Simulating the human eye in measurements of speckle from laser-based projection
      displays.
AB  - In quantitative measurement of the speckle observed in laser projection displays,
      it is essential how accurately one simulates the human eye. Based on the eye
      model given by Westheimer, we succeeded in simulating the optical transfer
      function of the eye model using that for the circular aperture. The equivalent
      circular aperture diameter is dependent on the eye model used in the simulation
      and its viewing conditions, but particularly for the eye models given by
      Westheimer and Williams, they substantially agreed, yielding approximately 1.2 mm
      at green under a 3 mm pupil diameter viewing condition.

PMID- 24921150
TI  - Photo and redox dual responsive reversibly cross-linked nanocarrier for efficient
      tumor-targeted drug delivery.
AB  - To develop a feasible and efficient nanocarrier for potential clinical
      application, a series of photo and redox dual responsive reversibly cross-linked
      micelles have been developed for the targeted anticancer drug delivery. The
      nanocarrier can be cross-linked efficiently via a clean, efficient, and
      controllable coumarin photodimerization within the nanocarrier, which simplify
      the formulation process and quality control prior clinical use and improve the in
      vivo stability for tumor targeting. At the same time, cross-linking of
      nanocarrier could be cleaved via the responsiveness of the built-in disulfide
      cross-linkage to the redox tumor microenvironment for on-demand drug release.
      Coumarin and disulfide bond was introduced into a linear-dendritic copolymer
      (named as telodendrimer) precisely via peptide chemistry. The engineered
      nanocarrier possesses good drug loading capacity and stability, and exhibits a
      safer profile as well as similar anticancer effects compared with free drug in
      cell culture. The in vivo and ex vivo small animal imaging revealed the preferred
      tumor accumulation and the prolonged tumor residency of the payload delivered by
      the cross-linked micelles compared to the non-cross-linked micelles and free drug
      surrogate because of the increased stability. 

PMID- 24921151
TI  - Single C8-Arylguanine modifications render oligonucleotides in the Z-DNA
      conformation under physiological conditions.
AB  - Z-DNA is the only DNA conformation that has a left-handed helical twist. Although
      Z-DNA has been implicated in both carcinogenesis and mutagenesis, its specific
      biological role remains uncertain. We have demonstrated that the formation of C8
      arylguanine DNA adducts, derived from arylhydrazines, shifts the B/Z-DNA
      equilibrium toward the Z-DNA conformation in d(CG)5 sequences. However, our
      previous work examined the effect of two adducts in the duplex, and it was
      unclear whether the two base modifications were working together to cause the
      equilibrium shift toward the Z-DNA conformation. Here we report the synthesis and
      characterization of a hairpin oligonucleotide sequence (d(CG)5T4(CG)5) containing
      only one C8-arylguanine modified base. The unmodified hairpin and the previously
      studied unmodified double-stranded oligonucleotide were conformationally similar,
      and each required ~3 M NaCl to yield a B-/Z-DNA ratio of 1:1. The introduction of
      a single C8-arylguanine modification significantly reduced the NaCl concentration
      needed to produce a 1:1 B-/Z-DNA ratio in the hairpin. Further, the addition of
      MgCl2 and spermine to the C8-arylguanine-modified hairpin shifts the B/Z-DNA
      equilibrium such that the Z form predominated under physiological conditions. NMR
      and molecular modeling indicated the conformational effects produced by the C8
      arylguanine modification occurred locally at the site of modification while CD
      data demonstrated that the C8-arylguanine-modified base destabilized the B form.
      Additionally, our data show that adopting the Z-DNA conformation is preferred
      over denaturation to the single-stranded form. Finally, the conformational
      effects of the C8-arylguanine modifications were not additive and the
      introduction of any such modifications drive Z-DNA formation under physiological
      conditions, which may provide a novel carcinogenesis mechanism where DNA adducts
      confer their carcinogenicity through a Z-DNA-mediated mechanism. 

PMID- 24921152
TI  - Copper dynamics in doped metal-bis(histidine) complexes.
AB  - Electron paramagnetic resonance (EPR) temperature-dependent measurements were
      undertaken on three Cu(II)-doped metal-histidine complexes to assess copper site
      dynamic behavior. Previous single-crystal EPR analysis on two of these, zinc d,l
      histidine pentahydrate (ZnDLH) and bis(l-histidinato)cadmium dihydrate (CdLH),
      found that doped Cu(2+) can be modeled as hopping between two neighboring
      conformational states, with a temperature-dependent rate becoming large enough at
      room temperature to produce an "averaged" spectrum. By comparing spectra from
      their powdered form, we show that Cu(2+) doped into a third system, Cd(2+)-d,l
      histidine (CdDLH), also exhibits temperature-dependent EPR with features
      indicating a similar motional-averaging process. In addition, the change of g and
      copper hyperfine parameters from low to high temperature for CdDLH resembles that
      in ZnDLH, whereas the change in these parameters for CdLH is like that found in a
      fourth copper-doped system, zinc l-histidine dihydrate (ZnLH). Taken together,
      these results suggest that averaging motion between neighboring copper sites is
      common in metal-bis(histidine) compounds. More detailed studies on biological
      models are thus warranted, especially because they reveal unique relationships
      between structure, dynamic processes, and stability and can lead to a better
      understanding of the role played by site flexibility in copper proteins. 

PMID- 24921153
TI  - Regulatory T-cell infiltration in tongue squamous cell carcinoma.
AB  - CONCLUSION: In tongue squamous cell carcinoma (SCC), high levels of regulatory T
      cell (Treg) infiltration in tumor nests are observed in the cases with poor
      prognosis. OBJECTIVES: The role of Tregs in head and neck cancers remains
      unclear. The aim of this study was to observe the distribution of Tregs in
      different stages of tongue SCC and estimate the effects on prognosis. METHODS:
      Thirty-four cases with tongue SCC were examined immunohistochemically for CD4,
      CD8, and Forkhead box P3 (Foxp3). Immunoreactive cells were counted in cancer
      stroma and nest regions, and relationships between cell numbers and disease-free
      survival rates were analyzed. RESULTS: In the 34 cases, univariate analysis for
      disease-free survival indicated high-level infiltration of Tregs (CD4(+)Foxp3+)
      into both cancer nests and stroma and presence of helper T (CD4(+)Foxp3-) cells
      in cancer stroma as potential predictors of significantly worse prognosis. In
      early-stage cases (stage I/II), high-level infiltration of Tregs in cancer nests
      correlated significantly with poor disease-free survival rate. Multivariate
      analysis for disease-free survival found no independent variables.

PMID- 24921154
TI  - Automated quantification of neurite outgrowth orientation distributions on
      patterned surfaces.
AB  - OBJECTIVE: We have developed an image analysis methodology for quantifying the
      anisotropy of neuronal projections on patterned substrates. APPROACH: Our method
      is based on the fitting of smoothing splines to the digital traces produced using
      a non-maximum suppression technique. This enables precise estimates of the local
      tangents uniformly along the neurite length, and leads to unbiased orientation
      distributions suitable for objectively assessing the anisotropy induced by
      tailored surfaces. MAIN RESULTS: In our application, we demonstrate that carbon
      nanotubes arrayed in parallel bundles over gold surfaces induce a considerable
      neurite anisotropy; a result which is relevant for regenerative medicine.
      SIGNIFICANCE: Our pipeline is generally applicable to the study of fibrous
      materials on 2D surfaces and should also find applications in the study of DNA,
      microtubules, and other polymeric materials.

PMID- 24921155
TI  - Gender differences in HIV disclosure, stigma, and perceptions of health.
AB  - HIV disclosure is a gateway to HIV prevention - particularly among couples living
      in regions severely affected by the HIV epidemic. This cross-sectional study
      utilizes data collected from 862 people living with HIV across three countries
      (Ethiopia, Mozambique, and Uganda) in 2011 to determine the role of partner
      disclosure on self-reported health perceptions and changes in sexual risk
      behavior. The study's secondary aims are to understand whether or not
      internalized stigma mediates this relationship and if there is a different
      pattern of results by gender. The multivariate analysis reveals that the three
      key HIV-related independent variables, belonging to a support group, doing
      volunteer work, and disclosing to one's spouse or partner, were significantly
      associated with lower levels of internalized stigma. Internalized stigma was
      associated with self-perceptions of poorer health for both women and men, with
      women reporting higher levels of internalized stigma than men. Disclosure to
      spouse was positively associated with perceptions of better health for women but
      not for men. For men, doing HIV-related volunteer work and disclosing their
      status to their spouse were positively associated with self-reported changes in
      sexual risk behavior, although stigma was not found to mediate this relationship.
      Findings from this study suggest that disclosure and stigma have gender-specific
      effects on individual well-being and changes in sexual risk behaviors. As such,
      programs must address gender inequity in disclosure patterns and stigma to
      enhance prevention efforts. 

PMID- 24921156
TI  - Dose-dependent inhibition of BACE-1 by the monoterpenoid 2,3,4,4-tetramethyl-5
      methylenecyclopent-2-enone in cellular and mouse models of Alzheimer's disease.
AB  - BACE-1 is an aspartic protease involved in the conversion of amyloid precursor
      protein (APP) to amyloid-beta (Abeta) in vivo, which is one of the key steps in
      the development and progression of Alzheimer's disease. In a previous screening
      procedure for inhibitors of BACE-1 activity, the oil of Lavandula luisieri was
      identified as the most potent among several essential oils. The inhibitory effect
      of this essential oil on Abeta production was also demonstrated in a cellular
      assay. The composition of the volatile oil and the isolation of the compound
      responsible for the inhibitory activity were also reported. The present work
      focused on the characterization of the inhibition of BACE-1 by this active
      compound, a monoterpene necrodane ketone, 2,3,4,4-tetramethyl-5
      methylenecyclopent-2-enone (1), with assessment of its Ki value and the type of
      inhibition. The dose-related effects of the compound were also evaluated using
      two different cell lines, with determinations of the respective EC50 values. The
      entire oil and the 2,3,4,4-tetramethyl-5-methylenecyclopent-2-enone (1) were
      tested on a triple transgenic mouse model of Alzheimer's disease. The overall
      results showed that compound 1 displayed a dose-dependent inhibition of BACE-1 in
      cellular and mouse models of Alzheimer's disease and is therefore capable of
      passing through cellular membranes and the blood-brain barrier. 

PMID- 24921157
TI  - Through-bond energy transfer cassettes for multicolor encoding.
AB  - Through-bond energy transfer (TBET) has been proposed as a versatile strategy to
      develop encoded microspheres. Together with the donor molecule, two TBET
      cassettes with high intramolecular TBET efficiencies (98% and 99%) and pseudo
      Stokes shifts about 70 and 160 nm have been codoped into PS microspheres. Upon
      exclusive excitation at 480 nm, these microspheres emit simultaneously triple
      peaks at 512, 570, and 656 nm. Further confocal imaging and flow cytometric
      analysis demonstrates satisfactory performances of the new encoded microspheres. 

PMID- 24921158
TI  - A hospice-hospital partnership: reducing hospitalization costs and 30-day
      readmissions among seriously ill adults.
AB  - BACKGROUND: Inpatient palliative care (IPC) has been associated with numerous
      clinical benefits. Observational and randomized studies of cost savings
      associated with IPC provide conflicting results, and the association with
      readmission is not well understood. OBJECTIVE: We aimed to estimate the influence
      of IPC on hospitalization costs and readmission rates. METHODS: We measured
      hospitalization costs and 30-day readmission rates among 1004 patients who
      received IPC at two western New York hospitals in 2012. Using propensity score
      matching, we compared outcomes among patients receiving palliative care with
      those among 1004 similar adults who were hospitalized during the same period and
      did not receive palliative care. RESULTS: On average, cost per admission was
      $1,401 (13%) lower among patients receiving palliative care than comparison
      patients (p<0.05). Cost reductions were evident within intensive care and
      laboratory services. Readmission rates were significantly lower among palliative
      care patients discharged with hospice care (1.1%) than comparison patients
      (6.6%), but significantly higher among palliative care patients discharged to
      other locations (12.1%). CONCLUSIONS: Receipt of IPC appears to reduce
      hospitalization costs among adult western New Yorkers. Furthermore, care
      coordinated with postdischarge hospice services appears to substantially reduce
      the likelihood of readmission.

PMID- 24921159
TI  - Two non-parametric methods for derivation of constraints from radiotherapy dose
      histogram data.
AB  - Dose constraints based on histograms provide a convenient and widely-used method
      for informing and guiding radiotherapy treatment planning. Methods of derivation
      of such constraints are often poorly described. Two non-parametric methods for
      derivation of constraints are described and investigated in the context of
      determination of dose-specific cut-points-values of the free parameter (e.g.,
      percentage volume of the irradiated organ) which best reflect resulting changes
      in complication incidence. A method based on receiver operating characteristic
      (ROC) analysis and one based on a maximally-selected standardized rank sum are
      described and compared using rectal toxicity data from a prostate radiotherapy
      trial. Multiple test corrections are applied using a free step-down resampling
      algorithm, which accounts for the large number of tests undertaken to search for
      optimal cut-points and the inherent correlation between dose-histogram points.
      Both methods provide consistent significant cut-point values, with the rank sum
      method displaying some sensitivity to the underlying data. The ROC method is
      simple to implement and can utilize a complication atlas, though an advantage of
      the rank sum method is the ability to incorporate all complication grades without
      the need for grade dichotomization. 

PMID- 24921160
TI  - Impurity-induced plasmon damping in individual cobalt-doped hollow Au nanoshells.
AB  - The optical properties of plasmonic nanoparticles in the size range corresponding
      to the electrostatic, or dipole, limit have the potential to reveal effects
      otherwise masked by phase retardation. Here we examine the optical properties of
      individual, sub-50 nm hollow Au nanoshells (Co-HGNS), where Co is the initial
      sacrificial core nanoparticle, using single particle total internal reflection
      scattering (TIRS) spectroscopy. The residual Co present in the metallic shell
      induces a substantial broadening of the homogeneous plasmon resonance line width
      of the Co-HGNS, where the full width at half-maximum (fwhm) broadens
      proportionately with increasing Co content. This doping-induced line broadening
      provides a strategy for controlling plasmon line width independent of
      nanoparticle size, and has the potential to substantially modify the relative
      decay channels for localized nanoparticle surface plasmons. 

PMID- 24921161
TI  - Speeding up directed evolution: Combining the advantages of solid-phase
      combinatorial gene synthesis with statistically guided reduction of screening
      effort.
AB  - Efficient and economic methods in directed evolution at the protein, metabolic,
      and genome level are needed for biocatalyst development and the success of
      synthetic biology. In contrast to random strategies, semirational approaches such
      as saturation mutagenesis explore the sequence space in a focused manner.
      Although several combinatorial libraries based on saturation mutagenesis have
      been reported using solid-phase gene synthesis, direct comparison with
      traditional PCR-based methods is currently lacking. In this work, we compare
      combinatorial protein libraries created in-house via PCR versus those generated
      by commercial solid-phase gene synthesis. Using descriptive statistics and
      probabilistic distributions on amino acid occurrence frequencies, the quality of
      the libraries was assessed and compared, revealing that the outsourced libraries
      are characterized by less bias and outliers than the PCR-based ones. Afterward,
      we screened all libraries following a traditional algorithm for almost complete
      library coverage and compared this approach with an emergent statistical concept
      suggesting screening a lower portion of the protein sequence space. Upon
      analyzing the biocatalytic landscapes and best hits of all combinatorial
      libraries, we show that the screening effort could have been reduced in all cases
      by more than 50%, while still finding at least one of the best mutants.

PMID- 24921162
TI  - Quality measures for hospice and palliative care: piloting the PEACE measures.
AB  - BACKGROUND: The Carolinas Center for Medical Excellence launched the PEACE
      project in 2006, under contract with the Centers for Medicare & Medicaid Services
      (CMS), to identify, develop, and pilot test quality measures for hospice and
      palliative care programs. OBJECTIVES: The project collected pilot data to test
      the usability and feasibility of potential quality measures and data collection
      processes for hospice and palliative care programs. Settings/subjects: Twenty-two
      hospices participating in a national Quality Improvement Collaborative (QIC)
      submitted data from 367 chart reviews for pain care and 45 chart reviews for
      nausea care. Fourteen additional hospices completed a one-time data submission of
      126 chart reviews on 60 potential patient-level quality measures across eight
      domains of care and an organizational assessment evaluating structure and
      processes of care. DESIGN: Usability was assessed by examining the range,
      variability and size of the populations targeted by each quality measure.
      Feasibility was assessed during the second pilot study by surveying data
      abstractors about the abstraction process and examining the rates of missing
      data. The impact of data collection processes was assessed by comparing results
      obtained using different processes. RESULTS: Measures shown to be both usable and
      feasible included: screening for physical symptoms on admission and documentation
      of treatment preferences. Methods of data collection and measure construction
      appear to influence observed rates of quality of care. CONCLUSIONS: We
      successfully identified quality measures with potential for use in hospices and
      palliative care programs. Future research is needed to understand whether these
      measures are sensitive to quality improvement interventions.

PMID- 24921163
TI  - Dietary intake, eating behaviors, and quality of life in women with polycystic
      ovary syndrome who are trying to conceive.
AB  - The Healthy Eating for Reproductive Health study was conducted among 18 (45% non
      white) mostly obese (BMI 39.9 +/- 6.1) women with polycystic ovary syndrome
      (PCOS) who were experiencing infertility and interested in losing weight. A
      variety of markers were measured at baseline: body mass index (BMI), diet,
      physical activity, eating behaviors (using an Eating Behavior Inventory, a
      questionnaire which assesses both positive and negative eating behaviors
      associated with weight status, with a higher score indicating adoption of eating
      behaviors which have been shown in prior weight-loss research to promote a
      healthy weight (EBI) and the Three-Factor Eating Questionnaire, which assesses
      cognitive and behavioral components of eating among overweight adults), and a
      quality of life (PCOS Health-Related Quality of Life (PCOSQ)) index, which
      assesses satisfaction around five 'domains': emotional health, presence of body
      hair, infertility, weight, and menstrual problems). A comparison group of
      overweight women without PCOS (n = 28) was used to examine differences in
      measured outcomes between women with and without PCOS. Participants' habitual
      diets were high in fat and saturated fat and low in fiber, folate, and iron and
      contained significantly lower amounts of carbohydrate, iron, and whole grains
      compared with women without PCOS who had enrolled in a behavioral weight loss
      programme. Participants had a low EBI (indicating that most were not adopting
      eating behaviors associated with achieving a healthy weight), disinhibition
      (indicating participants had a tendency to overeat in the presence of highly
      palatable foods or were susceptible to emotional cues for eating, such as
      stress), and hunger scores (indicating participants did not report being
      susceptible to hunger, prompting overeating) and moderate dietary restraint
      (indicating they were not consistently attempting to restrict food intake
      consciously). PCOSQ scores were lowest for infertility and weight domains
      (indicating low satisfaction with current infertility and weight status); however
      all domains received low scores (emotional health, body hair, and menstrual
      problems). Higher energy intakes (kcal/day) were associated with a lower EBI
      score (r = - 0.60, P = 0.02), lower dietary restraint (r =- 0.50, P = 0.04), and
      higher disinhibition (r = 0.63, P = 0.01). Greater energy expenditure (kcal/day)
      was associated with lower PCOSQ scores for body weight (r =-0.54, P = 002) and
      infertility (r =- 0.51, P = 0.003) domains. Results suggest that overweight women
      with PCOS-related infertility have poor dietary intake, particularly in terms of
      whole grains, fiber, and iron, and eating behaviors inconsistent with achieving a
      healthy body weight, as well as low scores for PCOS-related quality of life. 

PMID- 24921166
TI  - Treatment outcomes of monocular infantile cataract at 5-year follow-up: work in
      progress.

PMID- 24921167
TI  - A moving black spot in my vision.

PMID- 24921168
TI  - Man with blurry vision.

PMID- 24921169
TI  - Retinal reactive astrocytic tumor: gene expression profiling.

PMID- 24921170
TI  - Subretinal drusenoid deposits associated with complement-mediated IgA
      nephropathy.

PMID- 24921171
TI  - Loop-mediated isothermal amplification for rapid diagnosis of tubercular uveitis.

PMID- 24921172
TI  - Successful long-term management of iris flocculi and miosis in a patient with a
      strong family history of thoracic aortic aneurysms and dissections associated
      with an MYH11 mutation.

PMID- 24921173
TI  - Diffuse retinal ischemia following intravenous crushed oxymorphone abuse.

PMID- 24921174
TI  - Thin central corneal thickness and early-onset glaucoma in lacrimo-auriculo-dento
      digital syndrome.

PMID- 24921175
TI  - Association between rate of binocular visual field change and vision-related
      quality of life: novel finding or spurious association?

PMID- 24921176
TI  - Association between rate of binocular visual field change and vision-related
      quality of life--reply.

PMID- 24921177
TI  - Macular caldera in North Carolina macular dystrophy: only an illusion of
      posterior pole staphyloma.

PMID- 24921180
TI  - Macular caldera in North Carolina macular dystrophy--reply.

PMID- 24921181
TI  - Semiconductor-redox catalysis promoted by metal-organic frameworks for CO2
      reduction.
AB  - A noble-metal-free system for photochemical reduction of CO2 has been developed
      by integrating graphitic carbon nitride (g-C3N4) with a cobalt-containing
      zeolitic imidazolate framework (Co-ZIF-9). g-C3N4 acts as a semiconductor
      photocatalyst, whereas Co-ZIF-9 is a cocatalyst that facilitates the
      capture/concentration of CO2 and promotes light-induced charge separation. The
      two materials cooperate efficiently to catalyze CO2-to-CO conversion upon visible
      light illumination under mild reaction conditions. A (13)C-labelled isotropic
      experiment proved that CO2 is the carbon source of the produced CO. Even without
      noble metals, the system still achieved an apparent quantum yield of 0.9 percent.
      The system displayed high photocatalytic stability, without noticeable
      alterations in the chemical and crystal structures of g-C3N4 and Co-ZIF-9 after
      the reaction. 

PMID- 24921182
TI  - Silver-catalyzed synthesis of 3-phosphorated coumarins via radical cyclization of
      alkynoates and dialkyl H-phosphonates.
AB  - Ag2CO3-catalyzed difunctionalization of alkynes via a radical phosphonation and C
      H functionalization tandem process was developed to synthesize various 3
      phosphonated coumarins in moderate to high yields with high regioselectivity. A
      catalytic amount of cheap and nontoxic silver salt was employed in the domino C-P
      and C-C formation of alkynoates for the first time. Mechanistic studies indicate
      that the reaction pathway might proceed via the generation and cyclization of a
      phosphonated vinyl radical intermediate. 

PMID- 24921183
TI  - [Connective tissue diseases in hospital practice in Ouagadougou (Burkina Faso)].
AB  - To describe the semiological and immunological features of connective tissue
      diseases seen at the Yalgado Ouedraogo University Hospital in Ouagadougou. A
      retrospective study reviewed the records of patients seen in the hospital
      dermatology and internal medicine departments from January 1, 2004, through
      December 31, 2009 and diagnosed with systemic lupus erythematosus (SLE), systemic
      sclerosis (ScS), dermatopolymyositis (DPM), primary Gougerot-Sjogren disease
      (GS), polymyositis (PM) or indeterminate connective tissue disease (ICTD) meeting
      the criteria of the American College of Rheumatology. The study included 42
      patients, 36 women and 6 men. Their mean age was 41.2 years +/-11.97 (range: 15
      75). SLE was the diagnosis for 10 patients, ScS for 14, DPM for 7, primary GS for
      1, PM for 1, and ICTD for 9. Hematologic (93%), cutaneous (88%), and
      rheumatologic (81%) abnormalities were the most frequent manifestations. The
      specific auto-antibodies associated with SLE patients were: anti-native DNA
      (3/6), anti-Sm (3/6), anti-RNP (3/6), and anti-SSA (4/6); anti-Scl 70 antibodies
      were present in 5 patients with ScS. Connective tissue diseases seem to be rare
      in Africa, south of the Sahara. However, the very fragmentary studies and the
      weak healthcare coverage do not allow any definitive conclusions. 

PMID- 24921184
TI  - Reduction behavior of zinc ferrite in EAF-dust recycling with CO gas as a
      reducing agent.
AB  - EAF-dust containing metal oxides can be regarded as an important source for zinc
      and iron. In this study, the reduction behavior of zinc ferrite with CO gas as a
      reducing agent under different temperatures was investigated to develop a new
      process for the recovery of zinc and iron from EAF-dust. The results of the phase
      studies with synthetic franklinite show that zinc substituted wustite, and spinel
      with low zinc content formed at lower temperatures from 450 to 850  degrees C due
      to incomplete zinc-iron-separation. Zinc ferrite was completely reduced to
      metallic zinc and iron at 950  degrees C. After evaporation and condensation,
      metallic zinc was collected in the form of zinc powder while iron, the reduction
      residue, was obtained in the form of direct reduced iron (DRI). The mass balance
      indicates a high zinc recovery ratio of over 99%. The new treatment process by
      thermal reduction with CO gas as a reducing agent achieved higher recovery and
      metallization grade of both zinc and iron from EAF-dust at lower temperatures
      than other commercial processes. The metallic products can be used directly as
      semi-products or as raw materials for refinery. 

PMID- 24921186
TI  - Unique Responses are Observed in Transient Receptor Potential Ankyrin 1 and
      Vanilloid 1 (TRPA1 and TRPV1) Co-Expressing Cells.
AB  - Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1)
      receptors are implicated in modulation of cough and nociception. In vivo, TRPA1
      and TRPV1 are often co-expressed in neurons and TRPA1V1 hetero-tetramer formation
      is noted in cells co-transfected with the respective expression plasmids. In
      order to understand the impact of TRP receptor interaction on activity, we
      created stable cell lines expressing the TRPA1, TRPV1 and co-expressing the TRPA1
      and TRPV1 (TRPA1V1) receptors. Among the 600 compounds screened against these
      receptors, we observed a number of compounds that activated the TRPA1, TRPV1 and
      TRPA1V1 receptors; compounds that activated TRPA1 and TRPA1V1; compounds that
      activated TRPV1 and TRPA1V1; compounds in which TRPA1V1 response was modulated by
      either TRPA1 or TRPV1; and compounds that activated only TRPV1 or TRPA1 or
      TRPA1V1; and one compound that activated TRPA1 and TRPV1, but not TRPA1V1. These
      results suggest that co-expression of TRPA1 and TRPV1 receptors imparts unique
      activation profiles different from that of cells expressing only TRPA1 or TRPV1. 

PMID- 24921185
TI  - The cytolethal distending toxin effects on Mammalian cells: a DNA damage
      perspective.
AB  - The cytolethal distending toxin (CDT) is produced by many pathogenic Gram
      negative bacteria and is considered as a virulence factor. In human cells, CDT
      exposure leads to a unique cytotoxicity associated with a characteristic cell
      distension and induces a cell cycle arrest dependent on the DNA damage response
      (DDR) triggered by DNA double-strand breaks (DSBs). CDT has thus been classified
      as a cyclomodulin and a genotoxin. Whereas unrepaired damage can lead to cell
      death, effective, but improper repair may be detrimental. Indeed, improper repair
      of DNA damage may allow cells to resume the cell cycle and induce genetic
      instability, a hallmark in cancer. In vivo, CDT has been shown to induce the
      development of dysplastic nodules and to lead to genetic instability, defining
      CDT as a potential carcinogen. It is therefore important to characterize the
      outcome of the CDT-induced DNA damage and the consequences for intoxicated cells
      and organisms. Here, we review the latest results regarding the host cell
      response to CDT intoxication and focus on DNA damage characteristics, cell cycle
      modulation and cell outcomes. 

PMID- 24921187
TI  - The ufm1 cascade.
AB  - The ubiquitin-fold modifier 1 (Ufm1) is a posttranslational modifier that belongs
      to the ubiquitin-like protein (UBL) family. Ufm1 is present in nearly all
      eukaryotic organisms, with the exception of fungi. It resembles ubiquitin in its
      ability to be ligated to other proteins, as well as in the mechanism of ligation.
      While the Ufm1 cascade has been implicated in endoplasmic reticulum functions and
      cell cycle control, its biological role still remains poorly understood. In this
      short review, we summarize the current state of Ufm1 research and its potential
      role in human diseases, like diabetes, ischemic heart disease and cancer. 

PMID- 24921188
TI  - Luminescent metal-organic frameworks as explosive sensors.
AB  - Metal organic frameworks (MOFs) are of enormous current interest not only because
      of their fundamental importance but also due to their great potential for
      possible applications in gas storage and separation, catalysis, imaging and
      sensing, to name a few. Recent studies on luminescent MOFs (LMOFs) in both bulk
      and nanoparticle forms have shown that these materials possess excellent
      luminescence emission properties that may be utilized to effectively detect high
      explosive substances. Developing highly sensitive, selective, fast-responding and
      fully reversible sensors for explosives' detection is in great demand for the
      homeland security, environmental safety and other humanitarian concerns. In this
      perspective article, we discuss the development, possible mechanism and future
      aspects of explosive sensing by LMOF materials. 

PMID- 24921189
TI  - Monolingual and bilingual children with and without primary language impairment:
      core vocabulary comparison.
AB  - Core vocabulary is an important component of augmentative and alternative
      communication (AAC) systems for school-aged children who have complex
      communication needs. One method of identifying core vocabulary for these
      individuals is to study the vocabulary of speaking children. To date, the use of
      core vocabulary by speaking bilingual children has not been well documented. The
      present study compared the core vocabulary used by children who are monolingual
      (French), and bilingual (French-English; English-French). We also gathered and
      compared language samples from French-speaking children identified as having
      primary language impairment (PLI), with the goal of better understanding the
      language differences demonstrated by children with this disability. Language
      samples were collected from a total of 57 children within a school setting, in a
      region where French is a minority language. Contrary to the hypothesis, the
      analysis of language transcripts revealed that there were no important
      differences between the core words from the groups studied.

PMID- 24921190
TI  - Management of pregnancies in a hereditary angioedema patient after treatment with
      attenuated androgens since childhood.

PMID- 24921191
TI  - Effectiveness of a prematurity-based protocol for management of infants born to
      mothers with Group B Streptococcus colonisation.
AB  - The aim of this study was to validate the efficacy of a protocol for the
      management of infants born to colonised mothers with Group B Streptococcus (GBS).
      We studied a cohort of newborns admitted at the A. Gemelli University Hospital
      between May 2006 and December 2009. A total of 1,108 were newborns of mothers
      with GBS; 178 were children of mothers with unknown GBS status. Newborns were
      managed according to the care protocol in use at our division. Infected infants
      were born to mothers who underwent inadequate intrapartum antibiotic prophylaxis
      (IAP). No mother with complete IAP had an infected newborn. The incidence of
      invasive GBS infection in newborns of mothers with GBS was 0.4% and in newborns
      of mothers with unknown GBS status was 2.2%. Only 17.4% of newborns of mothers
      with GBS had risk factors. The complete IAP should always be performed regardless
      of the presence or the absence of risk factors. The care protocol applied offers
      successful management of the newborns of mothers with GBS, based on the correct
      execution of IAP, considering as a primary risk factor, the gestational age of <
      35 weeks.

PMID- 24921192
TI  - On the sustainability of an activity.
AB  - This paper develops a framework to determine the sustainability of a general
      activity. We define an activity as an action or process that uses one or more
      resources and that responds either wholly or partially to a demand. A definition
      for sustainability is developed and is contingent on whether or not an activity
      can be sustained according to the available resources, the duration of an
      activity, the cost of its execution, or whether substitution is possible. A
      sustainability condition is met when the duration, cost and the chain of
      dependent activities satisfies the demand. Two conditions for sustainability are
      developed: a strong condition when the demand is met with no substitution and a
      weak condition when the demand is met via substitution. In the latter case, we
      show that the set of all sustainable activities is a subset of a N-level union of
      sustainable activities and forms a topological cover. 

PMID- 24921193
TI  - Working toward a good life as a cancer survivor: a longitudinal study on positive
      health outcomes of a rehabilitation program for young adult cancer survivors.
AB  - BACKGROUND: Research on cancer rehabilitation targeting young adult cancer
      survivors (YACS) is limited, and little is known about the positive health
      outcomes of rehabilitation programs tailored specifically for this vulnerable
      group. OBJECTIVE: The aim of this study was to investigate whether a complex
      rehabilitation program improved the health-related quality of life (HRQOL) and
      physical capacities of YACS. METHODS: A longitudinal prospective study using
      Norwegian norm-based comparisons was conducted. Twenty YACS (24-35 years old)
      with different cancer diagnoses participated in a complex rehabilitation program
      lasting for 6 months, focusing on goal setting, exercise, psychoeducation,
      individual follow-up, and peer support. RESULTS: Health-related quality of life
      was measured by EORTC QOL C-30 and the scores showed significant increases in
      overall HRQOL (P < .005-.001) and all functional dimensions (P < .001-.05) and a
      decrease in fatigue (P < .000-.05) and effect sizes between 0.72 and 1.30.
      Significant changes occurred within physical fitness (P < .005), lung capacity (P
      < .05), and left-hand strength (P < .001), but not right-hand strength and body
      mass index, with effect sizes between -0.04 and 0.48. The values of HRQOL were
      stable after a 1-year follow-up. CONCLUSIONS: A complex cancer rehabilitation
      program especially tailored for YACS seems to build positive health outcomes such
      as HRQOL and physical capacity in a long-term perspective. The content and
      structure of the program were feasible with high compliance. The results
      underline the importance of targeting rehabilitation interventions to YACS in
      need after cancer treatment, acknowledging rehabilitation as a process that
      requires adequate time and follow-up. IMPLICATIONS FOR PRACTICE: Healthcare
      providers should be aware of YACS' symptom burden and monitor HRQOL and physical
      parameters to ascertain holistic cancer survivorship care.

PMID- 24921194
TI  - Exposure of Lycopersicon esculentum to microcystin-LR: effects in the leaf
      proteome and toxin translocation from water to leaves and fruits.
AB  - Natural toxins such as those produced by freshwater cyanobacteria have been
      regarded as an emergent environmental threat. However, the impact of these water
      contaminants in agriculture is not yet fully understood. The aim of this work was
      to investigate microcystin-LR (MC-LR) toxicity in Lycopersicon esculentum and the
      toxin accumulation in this horticultural crop. Adult plants (2 month-old) grown
      in a greenhouse environment were exposed for 2 weeks to either pure MC-LR (100
      MUg/L) or Microcystis aeruginosa crude extracts containing 100 MUg/L MC-LR.
      Chlorophyll fluorescence was measured, leaf proteome investigated with two
      dimensional gel electrophoresis and Matrix Assisted Laser Desorption Ionization
      Time-of-Flight (MALDI-TOF)/TOF, and toxin bioaccumulation assessed by liquid
      chromatography-mass spectrometry (LC-MS)/MS. Variations in several protein
      markers (ATP synthase subunits, Cytochrome b6-f complex iron-sulfur, oxygen
      evolving enhancer proteins) highlight the decrease of the capacity of plants to
      synthesize ATP and to perform photosynthesis, whereas variations in other
      proteins (ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit and
      ribose-5-phosphate isomerase) suggest an increase of carbon fixation and decrease
      of carbohydrate metabolism reactions in plants exposed to pure MC-LR and
      cyanobacterial extracts, respectively. MC-LR was found in roots (1635.21 MUg/kg
      fw), green tomatoes (5.15-5.41 MUg/kg fw), mature tomatoes (10.52-10.83 MUg/kg
      fw), and leaves (12,298.18 MUg/kg fw). The results raise concerns relative to
      food safety and point to the necessity of monitoring the bioaccumulation of water
      toxins in agricultural systems affected by cyanotoxin contamination. 

PMID- 24921195
TI  - A high-throughput, precipitating colorimetric sandwich ELISA microarray for Shiga
      toxins.
AB  - Shiga toxins 1 and 2 (Stx1 and Stx2) from Shiga toxin-producing E. coli (STEC)
      bacteria were simultaneously detected with a newly developed, high-throughput
      antibody microarray platform. The proteinaceous toxins were immobilized and
      sandwiched between biorecognition elements (monoclonal antibodies) and pooled
      horseradish peroxidase (HRP)-conjugated monoclonal antibodies. Following the
      reaction of HRP with the precipitating chromogenic substrate (metal enhanced 3,3
      diaminobenzidine tetrahydrochloride or DAB), the formation of a colored product
      was quantitatively measured with an inexpensive flatbed page scanner. The
      colorimetric ELISA microarray was demonstrated to detect Stx1 and Stx2 at levels
      as low as ~4.5 ng/mL within ~2 h of total assay time with a narrow linear dynamic
      range of ~1-2 orders of magnitude and saturation levels well above background.
      Stx1 and/or Stx2 produced by various strains of STEC were also detected following
      the treatment of cultured cells with mitomycin C (a toxin-inducing antibiotic)
      and/or B-PER (a cell-disrupting, protein extraction reagent). Semi-quantitative
      detection of Shiga toxins was demonstrated to be sporadic among various STEC
      strains following incubation with mitomycin C; however, further reaction with B
      PER generally resulted in the detection of or increased detection of Stx1,
      relative to Stx2, produced by STECs inoculated into either axenic broth culture
      or culture broth containing ground beef. 

PMID- 24921196
TI  - Bile salts at the air-water interface: adsorption and desorption.
AB  - Bile salts (BS) are bio-surfactants which constitute a vital component in the
      process of fat digestion. Despite the importance of the interfacial properties in
      their biological role, these have been scarcely studied in the literature. In
      this work, we present the adsorption-desorption profiles of two BS (NaTC and
      NaGDC) including dilatational rheology. Findings from this study reveal very
      different surface properties of NaTC and NaGDC which originate from different
      complexation properties relevant to the digestion process. Dynamic adsorption
      curves show higher adsorption rates for NaTC and suggest the existence of various
      conformational regimes in contrast to NaGDC which presents only one
      conformational regime. This is corroborated by analysis of the adsorption
      isotherms and more in detail by the rheological behaviour. Accordingly, the
      dilatational response at 1Hz displays two maxima of the dilatational modulus for
      NaTC as a function of bulk concentration, in contrast to NaGDC which displays
      only one maximum. The desorption profiles reveal that NaTC adopts an irreversibly
      adsorbed form at high surface coverage whereas NaGDC fully desorbs from the
      surface within the whole range of concentrations used. Analysis of the adsorption
      desorption profiles provides new insight into the surface properties of BS,
      suggesting a surface complexation of NaTC. This knowledge can be useful since
      through interfacial engineering we might control the extent of lipolysis
      providing the basis for the rational design of food products with tailored
      digestibility. 

PMID- 24921197
TI  - What interactions drive the salivary mucosal pellicle formation?
AB  - The bound salivary pellicle is essential for protection of both the enamel and
      mucosa in the oral cavity. The enamel pellicle formation is well characterised,
      however the mucosal pellicle proteins have only recently been clarified and what
      drives their formation is still unclear. The aim of this study was to examine the
      salivary pellicle on particles with different surface properties (hydrophobic or
      hydrophilic with a positive or negative charge), to determine a suitable model to
      mimic the mucosal pellicle. A secondary aim was to use the model to test how
      transglutaminase may alter pellicle formation. Particles were incubated with
      resting whole mouth saliva, parotid saliva and submandibular/sublingual saliva.
      Following incubation and two PBS and water washes bound salivary proteins were
      eluted with two concentrations of SDS, which were later analysed using SDS-PAGE
      and Western blotting. Experiments were repeated with purified transglutaminase to
      determine how this epithelial-derived enzyme may alter the bound pellicle.
      Protein pellicles varied according to the starting salivary composition and the
      particle chemistry. Amylase, the single most abundant protein in saliva, did not
      bind to any particle indicating specific protein binding. Most proteins bound
      through hydrophobic interactions and a few according to their charges. The
      hydrophobic surface most closely matched the known salivary mucosal pellicle by
      containing mucins, cystatin and statherin but an absence of amylase and proline
      rich proteins. This surface was further used to examine the effect of added
      transglutaminase. At the concentrations used only statherin showed any evidence
      of crosslinking with itself or another saliva protein. In conclusion, the
      formation of the salivary mucosal pellicle is probably mediated, at least in
      part, by hydrophobic interactions to the epithelial cell surface. 

PMID- 24921198
TI  - Healing at mandibular block-grafted sites. An experimental study in dogs.
AB  - AIM: The aim of this study was to evaluate the healing of autologous bone block
      grafts or deproteinized bovine bone mineral (DBBM) block grafts applied
      concomitantly with collagen membranes for horizontal alveolar ridge augmentation.
      MATERIAL AND METHODS: In six Labrador dogs, molars were extracted bilaterally,
      the buccal bony wall was removed, and a buccal box-shaped defect created. After 3
      months, a bony block graft was harvested from the right ascending ramus of the
      mandible and reduced to a standardized size. A DBBM block was tailored to similar
      dimensions. The two blocks were secured with screws onto the buccal wall of the
      defects in the right and left sides of the mandible, respectively. Resorbable
      membranes were applied at both sides, and the flaps sutured. After 3 months, one
      implant was installed in each side of the mandible, in the interface between
      grafts and parent bone. After 3 months, biopsies were harvested and ground
      sections prepared to reveal a 6-month healing period of the grafts. RESULTS: 77
      +/- 6.2% and 5.9 +/- 7.5% of vital mineralized bone were found at the autologous
      bone and DBBM block graft sites, respectively. Moreover, at the DBBM site, 63 +/-
      11.7% of connective tissue and 31 +/- 15.5% of DBBM occupied the area analyzed.
      Only 0.2 +/- 0.4% of DBBM was found in contact with newly formed bone. The
      horizontal loss was in a mean range of 0.9-1.8 mm, and 0.3-0.8 mm, at the
      autologous bone and DBBM block graft sites, respectively. CONCLUSIONS: Autologous
      bone grafts were vital and integrated to the parent bone after 6 months of
      healing. In contrast, DBBM grafts were embedded into connective tissue, and only
      a limited amount of bone was found inside the scaffold of the biomaterial.

PMID- 24921199
TI  - Novel Li2MnO3 nanowire anode with internal Li-enrichment for use in a Li-ion
      battery.
AB  - Anode materials which undergo a conversion reaction can achieve larger specific
      capacities than conventional carbon-based materials. They can even achieve higher
      energy densities when used at low voltages. However, the large amounts of Li2O
      generated in the interior of these structures when Li ions are inserted can cause
      volume expansion and mechanical fracturing from the inside out. This leads to a
      poor cycling performance and limits their commercial application. To overcome
      this limitation, we introduced Li ions into the interior of the cells of
      manganese oxide materials and successfully synthesized a novel Li-rich anode
      material (Li2MnO3). The reversible capacity reached 1279 mA h g(-1) after 500
      cycles, much higher than that of pure MnO2 or other commercial anodes. This
      optimization of the internal Li-enrichment and its application in Li2MnO3
      nanowires used as low voltage anodes in Li-ion batteries have rarely been
      reported. Further investigations by X-ray diffraction and photoelectron
      spectroscopy suggested that the strategy of optimizing the internal Li-enrichment
      of this novel Li2MnO3 anode is a promising development for Li-ion batteries.

PMID- 24921200
TI  - Proton-coupled electron transfer in azobenzene/hydrazobenzene couples with
      pendant acid-base functions. Hydrogen-bonding and structural effects.
AB  - Electron transfer in azobenzene derivatives bearing two carboxylic acid groups is
      coupled with intramolecular proton transfer in a stepwise manner in the title 2e(
      ) + 2H(+) redox couple. The presence of the pendant acid-base functions pushes
      the redox chemistry of the azo/hydrazo couple toward positive potentials by as
      much as 0.75 V. This is essentially the result of H-bonding of one of the
      nitrogen atoms by the neighboring carboxylic group and H-bonding of one
      carboxylate by the neighboring protonated nitrogen atom. The two electron
      transfer reactions, particularly the second one, are accompanied by strong
      structural changes, which results in the occurrence of a square scheme mechanism
      in which electron transfer and structural change are not concerted. These are
      typical phenomena that are likely to be encountered when attempting to boost
      proton-coupled electron-transfer stoichiometric or catalytic processes by
      installing pendant acid-base functionalities in the close vicinity of the
      reacting center. 

PMID- 24921201
TI  - Abdominal compartment syndrome in acute pancreatitis: a systematic review.
AB  - Abdominal compartment syndrome (ACS) is a lethal complication of acute
      pancreatitis. We performed a systematic review to assess the treatment and
      outcome of these patients.A systematic literature search for cohorts of patients
      with acute pancreatitis and ACS was performed. The main outcomes were number of
      patients with ACS, radiologic and surgical interventions, morbidity, mortality,
      and methodological quality.After screening 169 articles, 7 studies were included.
      Three studies were prospective and 4 studies were retrospective. The overall
      methodological quality of the studies was moderate to low. The pooled data
      consisted of 271 patients, of whom 103 (38%) developed ACS. Percutaneous drainage
      of intraabdominal fluid was reported as first intervention in 11 (11%) patients.
      Additional decompressive laparotomy was performed in 8 patients. Decompressive
      laparotomy was performed in a total of 76 (74%) patients. The median decrease in
      intraabdominal pressure was 15 mm Hg (range, 33-18 mm Hg). Mortality in acute
      pancreatitis patients with ACS was 49% versus 11% without ACS. Morbidity ranged
      from 17% to 90%.Abdominal compartment syndrome during acute pancreatitis is
      associated with high mortality and morbidity. Studies are relatively small and
      have methodological shortcomings. The optimal timing and method of invasive
      interventions, as well as their effect on clinical outcomes, should be further
      evaluated. 

PMID- 24921202
TI  - A systematic review of localization, surgical treatment options, and outcome of
      insulinoma.
AB  - OBJECTIVE: Insulinoma with an incidence of 0.4% is a rare pancreatic tumor.
      Preserving surgery is the treatment of choice. Exact localization is necessary to
      plan the appropriate approach. This article gives an overview on localization and
      surgical strategies for treatment of insulinoma. METHODS: In this systematic
      review, 114 articles with 6222 cases of insulinoma were reviewed with emphasis on
      localization techniques and surgical treatment. RESULTS: Insulinoma happens
      mostly in the fifth decade of life, with a higher incidence in men. They occur
      mostly sporadic (94%), benign (87%), and single (90%). Insulinomas are mostly
      smaller than 20 mm (84%). The tumors are distributed almost equally in the
      pancreas. CONCLUSIONS: Computed tomography is routinely used as first choice
      preoperatively. Intraoperative inspection, palpation, and sonography were applied
      with high success rate. Intraoperative sonography is considered as the most
      reliable technique. Enucleation is the most administered type of surgery (56%).
      Different types of resection include distal pancreatectomy (32%), Whipple
      procedure (3%), and subtotal pancreatectomy (<3%). Despite the development of
      laparoscopy, open approach is the favorite method (90%). The most common surgical
      complication is fistula. The mortality rate of open approach was higher (4 vs
      0%). Despite high cure rate, recurrence of insulinoma occurs in 7% after surgery.

PMID- 24921203
TI  - Use of sorafenib in a corticotropin-secreting pancreatic neuroendocrine
      carcinoma.

PMID- 24921204
TI  - Review of 43 patients with autoimmune pancreatitis based on the international
      consensus diagnostic criteria in China.

PMID- 24921205
TI  - The association of family history of cancer and medical history with pancreatic
      cancer risk.

PMID- 24921207
TI  - Intestinal microbiota: its role in digestive diseases.
AB  - It is now well known that intestinal microbiota exerts not only several
      physiological functions, but has also been implied in the mechanisms of many
      conditions, both intestinal and extraintestinal. These advances, to the best of
      our knowledge, have been made possible by the development of new ways of studying
      gut flora. Metagenomics, the study of genetic material taken directly from
      environmental samples, avoiding individual culture, has become an excellent tool
      to study the human microbiota. Therefore, it has demonstrated an association
      between an altered intestinal microbiota and inflammatory bowel disease or
      irritable bowel syndrome, perhaps the most extensively studied conditions
      associated with this particular subject. However, microbiota has a potential role
      in the development of other diseases; their manifestations are not confined to
      the intestine only. In this article, an extensive updated review is conducted on
      the role intestinal microbiota has in health and in different diseases. Focus is
      made on the following conditions: inflammatory bowel disease, irritable bowel
      syndrome, celiac disease, hepatic encephalopathy, and obesity. 

PMID- 24921206
TI  - Interplay between nuclear factor erythroid 2-related factor 2 and amphiregulin
      during mechanical ventilation.
AB  - Mechanical ventilation (MV) elicits complex and clinically relevant cellular
      responses in the lungs. The current study was designed to define the role of the
      transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a major
      regulator of the cellular antioxidant defense system, in the pulmonary response
      to MV. Nrf2 activity was quantified in ventilated isolated perfused mouse lungs
      (IPL). Regulation of amphiregulin (AREG) was investigated in BEAS-2B cells with
      inactivated Nrf2 or Keap1, the inhibitor of Nrf2, using a luciferase vector with
      AREG promoter. AREG-dependent Nrf2 activity was examined in BEAS-2B cells, murine
      precision-cut lung slices (PCLS), and IPL. Finally, Nrf2 knockout and wild-type
      mice were ventilated to investigate the interplay between Nrf2 and AREG during MV
      in vivo. Lung functions and inflammatory parameters were measured. Nrf2 was
      activated in a ventilation-dependent manner. The knockdown of Nrf2 and Keap1 via
      short hairpin RNA in BEAS-2B cells and an EMSA with lung tissue revealed that
      AREG is regulated by Nrf2. Conversely, AREG application induced a significant
      Nrf2 activation in BEAS-2B cells, PCLS, and IPL. The signal transduction of
      ventilation-induced Nrf2 activation was shown to be p38 MAP kinase-dependent. In
      vivo ventilation experiments indicated that AREG is regulated by Nrf2 during MV.
      We conclude that Areg expression is regulated by Nrf2. During high-pressure
      ventilation, Nrf2 becomes activated and induces AREG, leading to a positive
      feedback loop between Nrf2 and AREG, which involves the p38 MAPK and results in
      the expression of cytoprotective genes.

PMID- 24921208
TI  - Current diagnosis and management of the rumination syndrome.
AB  - The rumination syndrome is a behavioral condition characterized by postprandial
      regurgitation. In contrast to what many think, the disorder does not exclusively
      occur in mentally disabled patients or children but also in otherwise healthy
      adults. As symptoms of postprandial regurgitation are often mistaken for
      gastroesophageal reflux disease or vomiting, the rumination syndrome is an
      underappreciated condition. Rumination episodes are caused by an intragastric
      pressure increases which forces the gastric content into the esophagus and mouth
      and occurs during 3 distinct mechanisms: primary rumination, secondary
      rumination, and supragastric belch-associated rumination. Combined manometry
      impedance can distinguish rumination from gastroesophageal reflux disease.
      Treatment of the rumination syndrome consists of a thorough explanation of the
      mechanisms underlying the rumination episodes and behavioral therapy. As
      behavioral therapy is a time-consuming and often expensive treatment, we propose
      that a clinical suspicion of the disorder is always confirmed by a manometry
      impedance measurement.

PMID- 24921209
TI  - Novel endocuff-assisted colonoscopy significantly increases the polyp detection
      rate: a randomized controlled trial.
AB  - GOALS AND BACKGROUND: Screening colonoscopy for colorectal cancer has proven to
      reduce mortality rates. Recently the Endocuff (EC), an attachment to the distal
      tip of the colonoscope, was introduced. The aim of our study was to compare EC
      assisted colonoscopies with standard colonoscopies for the detection of colonic
      polyps. STUDY: This study is a randomized prospective 2-center trial. The study
      was conducted at 2 tertiary care centers. PARTICIPANTS: A total of 498 patients
      [249 males; median age 67 y; interquartile range (IQR), 56-75 y] for colon
      adenoma screening purposes were included. All patients underwent standard
      colonoscopy with or without the use of EC. Overall polyp detection rate, the
      number of colonic polyps, and the polyp distribution in the colon were measured.
      Difference in recognition of polyps with or without the use of EC was assessed.
      Statistical analysis was applied. RESULTS: In the EC group, the number of polyps
      detected per patient was 63% higher [2.00 (IQR, 1.00-4.00) vs. 1.00 (IQR, 1.00
      2.25), P<0.0001]. The polyp detection rate in patients increased by 14% with the
      use of EC (56% vs. 42%, P=0.001). For polyp detection, superiority by use of EC
      could be observed in the sigmoid (P=0.001) and cecum (P=0.002) for polyps <1 cm
      in diameter. In the EC group, the number of adenomas detected per patient
      significantly increased by 86% (P=0.002). No major complications occurred in both
      groups. CONCLUSIONS: The use of the EC is feasible and safe with significantly
      higher polyp detection rates, especially for those located in the sigmoid region.
      The cuff system has the potential to improve the accuracy of screening
      colonoscopies.

PMID- 24921210
TI  - Cirrhosis regression in patients with viral hepatitis B and C: a systematic
      review.
AB  - INTRODUCTION: Cirrhosis is a major milestone in patients with chronic liver
      disease because of its impact on patient morbidity and mortality. Chronic
      hepatitis B (CHB) and hepatitis C (CHC) are important causes of cirrhosis. This
      systematic review examines the relevant literature and evidence to assess whether
      cirrhosis can be reversible in patients with cirrhosis from viral hepatitis
      through long viral suppression. METHODS: A MEDLINE and Cochrane Library search
      was conducted to identify all articles pertinent to the subject matter. Fourteen
      publications were included in the final analysis: 4 hepatitis B studies and 10
      hepatitis C studies. Data abstracted from individual studies included patient
      demographics, antiviral therapy used, length of treatment, liver biopsy scoring
      system, length of biopsy, and time between biopsies. RESULTS: In CHB, the 7
      studies reviewed included a total of 463 cirrhotic patients. Regression of
      cirrhosis was noted in a median of 70% (range, 33% to 80%) of patients. In CHC,
      the 13 studies reviewed included a total of 58 cirrhotic patients. Regression of
      cirrhosis was seen in a median of 64% (range, 33% to 100%) of patients with
      sustained viral response. CONCLUSIONS: The results of our review suggest that
      viral suppression in CHB and sustained virologic response in CHC can be
      associated with histologic regression of cirrhosis in select patients.

PMID- 24921211
TI  - Clarithromycin Versus Metronidazole as First-line Helicobacter pylori
      Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.
AB  - BACKGROUND: Helicobacter pylori eradication rates achieved with a first-line
      regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump
      inhibitor have recently fallen to <=80% because of the increasing incidence of
      CLR resistance in Japan. This randomized multicenter trial aimed to compare the
      eradication success of 2 first-line triple therapy regimens: rabeprazole,
      amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and
      metronidazole (RAM). METHODS: A total of 124 consecutive patients infected with
      H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60)
      or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse
      effects were also assessed. RESULTS: Intention-to-treat and per protocol H.
      pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the
      RAM group. The eradication rate of RAM therapy was significantly higher than that
      of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%,
      and 0% of patients, respectively. In addition, no relevant differences in adverse
      effects were observed. CONCLUSIONS: Metronidazole-based therapy (RAM) was
      superior to standard CLR-based therapy (RAC) for first-line H. pylori
      eradication. This reflects the progressive increase in CLR resistance observed in
      Japan.

PMID- 24921212
TI  - World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver
      disease and nonalcoholic steatohepatitis.

PMID- 24921213
TI  - Use of sunitinib in a 30-year-old woman with pancreatic neuroendocrine tumors
      associated with Von Hippel-Lindau syndrome.

PMID- 24921214
TI  - Liver and pancreatic cancer related to hepatitis B exposure: has the jury reached
      a verdict?

PMID- 24921215
TI  - Current challenges and the management of chronic hepatitis C in mainland China.
AB  - Despite decreasing prevalence, new cases of hepatitis C in China are increasing
      recently with growing percentage of patients who are with advanced disease,
      aging, or not eligible for interferon-based treatments. Hepatitis C infection
      represents a serious public health burden. This review was based on expert's
      consensus during a medical forum on hepatitis sponsored by the Beijing Wu Jie
      Ping Medical Foundation. The literature searches were conducted in PubMed and
      critical publications in Chinese journals. Data on hepatitis C prevalence, risk
      factors, viral or host features, and treatment modalities were extracted and
      reviewed. Recent large-scale surveys reported reducing prevalence of hepatitis C
      to approximately 0.4% in China, partly because of regulation changes to safer
      medical practices and illegalizing commercial blood donations. Patient
      demographics evolved from being dominated by former paid blood donors to include
      intravenous drug users and others. Although hepatitis C genotype 1 is the most
      common, other genotypes are emerging in prevalence. The current standard of care
      is interferon-based without direct acting antivirals. However, many patients
      failed therapy because of high treatment costs, substantial needs to manage side
      effects, difficulties with treatment monitoring in the rural areas, and growing
      populations of elderly and cirrhotic patients. The lack of high efficacy
      therapies with good safety profile and low disease awareness in China resulted in
      increasing public burden of advanced hepatitis C disease. Despite significant
      reduction of hepatitis C prevalence, iatrogenic, nosocomial, and community
      transmissions are still significant. In addition to promoting disease awareness,
      interferon-free regimens are needed to reduce the public health burden. 

PMID- 24921216
TI  - Nanomaterial-induced autophagy: a new reversal MDR tool in cancer therapy?
AB  - Most of the therapeutic strategies to counteract cancer imply killing of
      malignant cells. The most exploited cell death mechanism in cancer therapies is
      apoptosis, but recently, a lot of papers report that other mechanisms, mainly
      autophagy, could represent a new line of attack in the fight against cancer. One
      of the limitations for the effectiveness of the approved clinical treatments is
      the phenomenon of multidrug resistance (MDR) which enables the cancer cells to
      develop resistance to therapy, especially for chemotherapy. The MDR mechanisms
      include (a) decreased uptake of drug, (b) reduced intracellular drug
      concentration by efflux pumps, (c) altered cell cycle checkpoints, (d) altered
      drug targets, (e) increased metabolism of drugs, (f) induced emergency response
      genes to impair apoptotic pathway, and (g) altered drug detoxification. Great
      efforts have been made to reverse MDR. Currently, autophagy and nanosized drug
      delivery systems (DDSs) belonging to nanomaterials (NMs) provide alternative
      strategies to circumvent MDR. Nanosized DDSs are very promising tools to
      accumulate chemotherapeutics at targeting sites and control temporal and spatial
      drug release into tumor cells. On the other hand, autophagy could overrule drug
      resistance upon its activation by ensuring cell death via switching its
      prosurvival role to a prodeath one or by mediating the occurrence of cell death,
      i.e., apoptosis or necrosis. Likewise, the autophagy inhibition could counteract
      MDR by sensitizing the cells to anticancer molecules, i.e., Src family tyrosine
      kinase (SFK) inhibitors or 5-fluorouracil. Noteworthy, autophagy has been
      recently indicated to be a common cellular response to NMs, corroborating the
      fascinating idea of the exploitation of NM-induced autophagy in nanomedicine
      therapy. This review focuses on recently published literature about the
      relationship between MDR reversal and NMs or autophagy pointing to hypothesize a
      pivotal role of autophagy modulation induced by NMs in counteracting MDR. 

PMID- 24921219
TI  - Iron-nitrogen-doped mesoporous tungsten carbide nanostructures as oxygen
      reduction electrocatalysts.
AB  - Since Pt-based catalysts have the disadvantages of high cost, large overpotential
      loss, and limited long-term stability, there have been various promising
      alternatives to Pt-based catalysts to improve the catalytic activity towards the
      oxygen reduction reaction (ORR). We have synthesized iron-nitrogen-doped
      mesoporous tungsten carbide catalysts (WC-m-FT) by pyrolysis of well-ordered
      mesoporous tungsten carbides with iron porphyrin. WC-m-FT exhibits excellent ORR
      catalytic activity in an alkaline medium, i.e. a high electron-transfer number as
      well as superior stability and methanol tolerance. The improved activity and
      stability of WC-m-FT are ascribed to iron-containing catalytic active sites
      surrounded by nitrogen species and the well-defined mesoporous tungsten carbide
      structure. 

PMID- 24921218
TI  - Outcome of Transplant-fallout Patients With Unresectable Cholangiocarcinoma.
AB  - OBJECTIVES: The aim of this was to determine survival after starting neoadjuvant
      therapy for patients who became ineligible for orthotopic liver transplantation
      (OLT). METHODS AND MATERIALS: Since January 1993, 215 patients with unresectable
      cholangiocarcinoma began treatment with planned OLT. Treatment included external
      beam radiation therapy (EBRT) with fluorouracil, bile duct brachytherapy, and
      postradiotherapy fluorouracil or capecitabine before OLT. Adverse findings at the
      staging operation, death, and other factors precluded OLT in 63 patients (29%),
      of whom 61 completed neoadjuvant chemoradiation. RESULTS: By October 2012, 56
      (89%) of the 63 patients unable to undergo OLT had died. Twenty-two patients
      (35%) became ineligible for OLT before the staging operation, 38 (60%) at the
      staging operation, and 3 (5%) after staging. From the date of diagnosis, median
      overall survival was 12.3 months. Survival was 17% at 18 months and 7% at 24
      months. Median survival after fallout was 6.8 months. Median survival after the
      staging operation was 6 months. Two patients lived for 3.7 and 8.7 years before
      dying of cancer or liver failure caused by persistent biliary stricture at the
      site of the original cancer, respectively. Univariate analysis showed that time
      from diagnosis to fallout correlated with overall survival (P=0.04). CONCLUSIONS:
      In highly selected patients initially suitable for OLT, the mortality rate for
      cholangiocarcinoma was high in patients who became ineligible for OLT. Their
      survival, however, was comparable to expected survival for patients with locally
      advanced or metastatic disease treated with nontransplant therapies. The most
      common reason for patient fallout was adverse findings at the staging operation.

PMID- 24921217
TI  - Wnt coreceptor Lrp5 is a driver of idiopathic pulmonary fibrosis.
AB  - RATIONALE: Wnt/beta-catenin signaling has been implicated in lung fibrosis, but
      how this occurs and whether expression changes in Wnt pathway components predict
      disease progression is unknown. OBJECTIVES: To determine whether the Wnt
      coreceptor Lrp5 drives pulmonary fibrosis in mice and is predictive of disease
      severity in humans. METHODS: We examined mice with impaired Wnt signaling caused
      by loss of the Wnt coreceptor Lrp5 in models of lung fibrosis induced by
      bleomycin or an adenovirus encoding an active form of transforming growth factor
      (TGF)-beta. We also analyzed gene expression in peripheral blood mononuclear
      cells (PBMC) from patients with idiopathic pulmonary fibrosis (IPF). MEASUREMENTS
      AND MAIN RESULTS: In patients with IPF, analysis of peripheral blood mononuclear
      cells revealed that elevation of positive regulators, Lrp5 and 6, was
      independently associated with disease progression. LRP5 was also associated with
      disease severity at presentation in an additional cohort of patients with IPF.
      Lrp5 null mice were protected against bleomycin-induced pulmonary fibrosis, an
      effect that was phenocopied by direct inhibition of beta-catenin signaling by the
      small molecular inhibitor of beta-catenin responsive transcription.
      Transplantation of Lrp5 null bone marrow cells into wild-type mice did not limit
      fibrosis. Instead, Lrp5 loss was associated with reduced TGF-beta production by
      alveolar type 2 cells and leukocytes. Consistent with a role of Lrp5 in the
      activation of TGF-beta, Lrp5 null mice were not protected against lung fibrosis
      induced by TGF-beta. CONCLUSIONS: We show that the Wnt coreceptor, Lrp5, is a
      genetic driver of lung fibrosis in mice and a marker of disease progression and
      severity in humans with IPF. Evidence that TGF-beta signaling can override a loss
      in Lrp5 has implications for patient selection and timing of Wnt pathway
      inhibitors in lung fibrosis.

PMID- 24921220
TI  - Transoral robotic surgery for obstructive sleep apnea in Asian patients: a
      Singapore sleep centre experience.
AB  - IMPORTANCE: This study investigates the effectiveness of combined palatal surgery
      and transoral robotic surgical (TORS) tongue base reduction with partial
      epiglottidectomy in the treatment of obstructive sleep apnea (OSA) in an Asian
      context. To our knowledge, this is the first report on TORS for OSA in Asian
      patients in the literature. OBJECTIVE: To report our preliminary experience with
      combined TORS tongue base reduction and partial epiglottidectomy with palatal
      surgery as a multilevel surgical treatment strategy for moderate to severe OSA in
      Asian patients for whom positive airway pressure treatment had failed. DESIGN,
      SETTING, AND PARTICIPANTS: A retrospective study of prospectively collected data
      on 40 Asian patients who underwent primary TORS tongue base reduction with
      partial epiglottidectomy and palatal surgery for treatment of moderate to severe
      OSA at an academic tertiary surgical center. INTERVENTIONS: Transoral robotic
      surgery and palatal surgery for surgical management of OSA in patients for whom
      positive airway pressure treatment had failed. MAIN OUTCOMES AND MEASURES: Twenty
      patients with complete preoperative and postoperative overnight polysomnograms
      were evaluated for surgical success and cure, according to traditional surgical
      criteria, and for subjective outcome measures (snoring and satisfaction on visual
      analog scale [VAS] and Epworth Sleepiness Scale [ESS]) as well as complications.
      RESULTS: Traditional cure (apnea-hypopnea index [AHI] <5/h) was achieved in 7 of
      20 patients (35%), traditional success (AHI <20 [>50% reduction in AHI]) was
      achieved in another 11 patients (55%), and failure was observed in 2 patients
      (10%). Subjective improvement in snoring, satisfaction, and ESS score was
      observed. Improvement in mean (SD) ESS score and snoring loudness on VAS were
      statistically significant, from 12.4 (2.87) to 6.4 (1.43) and 8.7 (0.8) to 3.5
      (1.7), respectively (P < .001 for both). None of the patients needed
      postoperative tracheostomy. Recorded complications included tonsillar fossa
      bleeding, pain, temporary dysgeusia, numbness of the tongue, and temporary
      dysphagia. CONCLUSIONS AND RELEVANCE: Transoral robotic surgery for tongue base
      reduction and partial epiglottidectomy for moderate to severe OSA in Asian
      patients for whom positive airway pressure treatment had failed is associated
      with good efficacy and low complication rates.

PMID- 24921221
TI  - Flux growth of Yb(6.6)Ir(6)Sn(16) having mixed-valent ytterbium.
AB  - The compound Yb6.6Ir6Sn16 was obtained as single crystals in high yield from the
      reaction of Yb with Ir and Sn run in excess indium. Single-crystal X-ray
      diffraction analysis shows that Yb6.6Ir6Sn16 crystallizes in the tetragonal space
      group P42/nmc with a = b = 9.7105(7) A and c = 13.7183(11) A. The crystal
      structure is composed of a [Ir6Sn16] polyanionic network with cages in which the
      Yb atoms are embedded. The Yb sublattice features extensive vacancies on one
      crystallographic site. Magnetic susceptibility measurements on single crystals
      indicate Curie-Weiss law behavior <100 K with no magnetic ordering down to 2 K.
      The magnetic moment within the linear region (<100 K) is 3.21 MUB/Yb, which is
      ~70% of the expected value for a free Yb(3+) ion suggesting the presence of mixed
      valent ytterbium atoms. X-ray absorption near edge spectroscopy confirms that
      Yb6.6Ir6Sn16 exhibits mixed valence. Resistivity and heat capacity measurements
      for Yb6.6Ir6Sn16 indicate non-Fermi liquid metallic behavior. 

PMID- 24921222
TI  - Electrochemical quantification of iodide ions in synthetic urine using silver
      nanoparticles: a proof-of-concept.
AB  - Typical urinary iodide concentrations range from 0.3 MUM to 6.0 MUM. The
      conventional analytical method is based on the Sandell-Kolthoff reaction. It
      involves the toxic reagent, arsenic acid, and a waiting time of 30 minutes for
      the iodide ions to reduce the cerium(iv) ions. In the presented work, an
      alternative fast electrochemical method based on a silver nanoparticle modified
      electrode is proposed. Cyclic voltammetry was performed with a freshly modified
      electrode in presence of iodide ions and the voltammetric peaks corresponding to
      the oxidation of silver to silver iodide and the reverse reaction were recorded.
      The peak height of the reduction signal of silver iodide was used to plot a
      calibration line for the iodide ions. Two calibration plots for the iodide ions
      were obtained, one in 0.1 M sodium nitrate (a chloride-ion free environment to
      circumvent any interference from the other halides) and another in synthetic
      urine (which contains 0.2 M KCl). In both of the calibration plots, linear
      relationships were found between the reduction peak height and the iodide ion
      concentration of 0.3 MUM to 6.0 MUM. A slope of 1.46 * 10(-2) A M(-1) and a R(2)
      value of 0.999 were obtained for the iodide detection in sodium nitrate. For the
      synthetic urine experiments, a slope of 3.58 * 10(-3) A M(-1) and a R(2) value of
      0.942 were measured. A robust iodide sensor with the potential to be developed
      into a point-of-care system has been validated. 

PMID- 24921224
TI  - Editorial.

PMID- 24921223
TI  - Assessment for ease of use and preference of a new prefilled insulin pen
      (FlexTouch Degludec U100/U200) versus the SoloSTAR insulin pen by patients with
      diabetes and healthcare professionals.
AB  - OBJECTIVE: FlexTouch(r) (FT) is a new prefilled insulin pen with no push-button
      extension and a low injection force used to deliver several basal insulins,
      including insulin degludec across a wide dose range (1 - 80 units with FT 100
      IU/ml [FT100] and 2 - 160 units with 200 IU/ml [FT200]). This study was carried
      out to evaluate whether the novel features of FT affect the preferences of the
      device among patients with diabetes and healthcare professionals compared with
      the widely used SoloSTAR(r) pen. RESEARCH DESIGN AND METHODS: A multicenter,
      randomized, open-label, crossover study compared FT100 and FT200 with SoloSTAR.
      The study included patients with either type 1 (n = 22) or type 2 diabetes (n =
      42), nurses (n = 32) and physicians (n = 32). Subjects were randomized to test
      each of the FT100, FT200 and SoloSTAR pens in a crossover set up. Subjects
      performed injections into a foam cushion at 4 - 6 different doses per device (2,
      20, 40, 80, 120 and 160 IU). RESULTS: Overall, a significantly higher proportion
      of subjects, including dexterity-impaired and pen-naive patients, preferred to
      use FT100 (93.0%; 119/128) and FT200 (91.4%; 117/128) compared with 2.3% (3/128)
      and 3.9% (5/128) who preferred SoloSTAR (p < 0.001), respectively. CONCLUSION:
      FT100 and FT200 were preferred over SoloSTAR by nurses, physicians and patients
      with diabetes. This may be due to the novel design of FT, which improves ease of
      use, preference and confidence in delivering a complete, accurate dose of
      insulin, even at high doses.

PMID- 24921225
TI  - Psychotropic medications and HIV medicine: A rational approach.
AB  - New drugs available for HN infection treatment have produced significant
      improvements in quality and quantity of life in affected individuals. These new
      agents are metabolized by the same hepatic microsomal system that is responsible
      for breakdown of psychotropic drugs. Thus, toxic drug levels and undesirable side
      effects are possible when anti-retroviral drugs are used in combination with
      psychotropic medication. The treatment of HN-infected individuals presenting with
      neuropsychiatric and psychological morbidity is reviewed. A rational approach
      should involve the selection of drugs that minimize interaction with metabolism
      of the other medications. 

PMID- 24921226
TI  - The pharmaco-economics of atypical antipsychotics.
AB  - Atypical antipsychotics are claimed to show advantages in efficacy and
      tolerability when compared with older, typical drugs. However, the purchase cost
      of atypicals far exceeds that of typical drugs. Pharmaco-economic evaluations of
      the use of atypical agents are used, in essence, to determine whether or not the
      benefit gained by using atypicals is greater than the extra cost of their
      acquisition. Several forms of pharmaco-economic evaluation have been developed,
      but none provides definitive, unarguable findings. In psychiatry, the most
      commonly used method is the mirror-image technique, which retrospectively
      compares costs and outcomes before and after the use of a particular drug.
      Despite the large number of phamacoeconomic evaluations undertaken and published,
      the cost-effectiveness of atypical drugs remains unproven. Data relating to
      clozapine are the most compelling, but they remain ultimately equivocal. However,
      ethical considerations may prevent conclusive research being conducted. Some data
      support the cost-effectiveness of olanzapine and risperidone, but, again, the
      overall picture is far from clear. Little or nothing is known of the pharmaco
      economics of other atypicals. Further research is needed before any atypical can
      be said to be cost-effective. 

PMID- 24921227
TI  - Valproic acid for seizure prophylaxis during clozapine therapy: Where's the
      evidence?
AB  - Clozapine, a dibenzodiazepine derivative, is the prototype atypical antipsychotic
      indicated for treatment-resistant patients with schizophrenia. Although
      considered by many to be the most effective antipsychotic, its clinical use has
      been hindered by some serious adverse reactions, one of the more serious of which
      is seizures. In response to this inherent risk of clozapine-induced seizures,
      some clinicians have been advocating the use of prophylactic valproic acid
      treatment. This article reviews the available literature to assess the evidence
      to support this practice. 

PMID- 24921228
TI  - Suicidal ideation amongst functionally ill psychogeriatric inpatients.
AB  - OBJECT: Fluctuating suicidal ideation can undermine the accuracy of suicide risk
      assessment. METHOD: This pilot study examined fluctuations in suicidal ideation
      among psychogeriatric inpatients as reported by nurses, doctors and the patients
      themselves. The relationship between these reports of suicidal ideation is also
      examined. RESULTS: Five (38%) patients exhibited fluctuations in suicidal
      ideation. Doctors reported greater suicidal ideation than did the nurses and
      patients. CONCLUSION: Clinical implications of this discrepancy and fluctuations
      in suicidal ideation are discussed.

PMID- 24921229
TI  - Assessment of sexual dysfunction in depressed patients and reporting attitudes in
      routine daily practice: Results of the postmarketing observational studies with
      moclobemide, a reversible MAO-A inhibitor.
AB  - OBJECT: The aim of this study was to assess the effect of moclobemide on sexual
      dysfunction in depressed patients treated under routine conditions in private
      practice and hospital settings. METHOD: sexual function was systematically
      assessed by a specific questionnaire and by recording spontaneously reported
      adverse events during large prospective postmarketing surveillance studies with
      moclobemide, carried out in Germany between 1992 and 1995. The data of 4333
      patients were collected in two different settings: (a) specialized psychiatric
      and neurological private practices and (b) psychiatric hospitals. RESULTS: Up to
      70% of depressed patients suffered from Some type of sexual dysfunction at
      baseline and in about two thirds the dysfunction was rated as moderate to severe.
      The severity and frequency of sexual dysfunction corresponded well to the
      severity of depressive syndrome. Sexual functions improved during treatment with
      moclobemide and the extent of improvement corresponded to the favourable outcome
      of antidepressant treatment. Deterioration of sexual functions under moclobemide
      treatment was infrequent and experienced by less than 3% of patients. The
      frequency of spontaneously reported sexual dysfunction, reported as adverse
      event, was lower than 0.1%. For a considerable proportion of patients included in
      the studies sexual function was not systematically recorded: up to 10-20% of data
      for variables related to sexual function were missing. Unreported sexual
      functioning varied in dependence of the type of function, age and gender of the
      patient and treatment settings. CONCLUSION: The results of the observational
      studies with moclobemide do not provide evidence that moclobemide induces or
      intensifies sexual dysfunction in depressed patients under routine daily
      treatment. The results also demonstrate that the assessment of sexual function in
      the practice is clearly influenced by the reporting attitudes of patients and
      physicians.

PMID- 24921230
TI  - Medically unexplained chronic musculoskeletal pain and psychiatric morbidity in
      an Indian sample.
AB  - OBJECT: The psychiatric aspects of 30 patients suffering from chronic
      musculoskeletal pain in a Government hospital in Mumbai, India were investigated.
      METHOD: Twenty-three relatives matched for age and sex formed a control group.
      The Structured Clinical Interview for DSM-III-R (SCID-I) was used to determine
      the nature of the psychiatric morbidity. The role of stressful fife events was
      examined using the Presumptive Stressful Life Events Scale (PSLES). RESULTS: More
      than half the patients satisfied the criteria for a depressive disorder. The
      patients experienced a higher number of stressful life events than the control
      group. The patients were further categorized as 'depressed' or 'non-depressed',
      and their pain estimates compared by using the Smith's submaximum tourniquet
      technique. The depressed patients had experienced a higher number of stressful
      life events and higher pain estimates than the non-depressed patients.
      CONCLUSION: The results are discussed in relation to mental illness, life events
      and the experience of chronic pain.

PMID- 24921231
TI  - Algorithm for the treatment of schizophrenia in Japan.
AB  - Evidence-based psychopharmacological algorithms for the treatment of patients
      with schizophrenia have been developed in many countries in the last decade.
      While it would be of interest to consider a common algorithm based on
      international consensus, algorithms and information on antipsychotics available
      in each country are limited. Inspired by the algorithm generated by the
      International Psychopharmacology Algorithm (IPA) Project, this algorithm for the
      treatment of schizophrenia has been developed by the Japan Psychophamacology
      Algorithm (JPA) Project. New antipsychotics, such as clozapine, olanzapine and
      quetiapine, are excluded from this algorithm, being currently unavailable in
      Japan. In the end there was no essential difference between the algorithms for
      the treatment of acute schizophrenic episodes. However, combined use of
      antipsychotics appears to be more common in Japan and the adjunctive use of L
      DOPS or thyrotropin-releasing hormone is included in the JPA algorithm for the
      treatment of drug-refractory schizophrenia. 

PMID- 24921232
TI  - Algorithm for the treatment of mood disorders in Japan.
AB  - In order to establish algorithms for mood disorders in Japan, over 300
      psychiatrists completed a questionnaire. They were asked to recommend various
      drug treatments for particular cases. The order in which the drugs were
      recommended was taken into consideration. References were made to the randomized
      double blind study conducted by the working group. Evidence was ranked according
      to its probability, with the addition of case reports and medical opinions, since
      conclusions derived from the randomized double blind study alone did not give a
      full representation. Japanese documentation was referred to as much as possible
      in order to represent Japanese characteristics. Algorithms were made for eight
      subtypes; acute mania, bipolar depression, mild or moderate, severe major
      depression, psychotic depression, rapid cycling bipolar disorder, dysthymic
      disorder and major depression with advanced cancer. Major depression and bipolar
      disorder algorithms are discussed in this paper. Clinical psychopharmacological
      evidence in Japan was insufficient to generate these algorithms for mood
      disorders. These algorithms may need revision according to future advances in
      clinical psychopharmacology. (Int J Psych Clin Pract 1999; 3: 277-285). 

PMID- 24921233
TI  - A sertraline/valproic acid drug interaction: Case Reports.
AB  - Clinicians are frequently faced with the challenge of treating patients diagnosed
      within the wide spectrum of bipolar depression. Because no one single mood
      stabilizing agent can effectively treat depression, and antidepressant agents can
      trigger mania, these classes are employed together to treat bipolar depression.
      Because psychotropic medications are frequently mixed in treating a wide variety
      of psychiatric conditions, clinicians must remain vigiliant for possible drug
      interactions, which can cause unnecessary morbidity. A case is reported in which
      a patient suffering from bipolar depression experienced a drug interaction
      involving sertraline and valproic acid. To date there have been no reported cases
      of drug interactions between these two psychotropic medications. (Int J Psych
      Clin Pract 1999; 3: 287-288). 

PMID- 24921234
TI  - A case of reversal of treatment-resistant depression after almost 30 years of
      symptoms: Case Reports.
AB  - The introduction of antidepressants constituted a breakthrough in the treatment
      of depression. Despite their success, a significant proportion of patients
      respond partially or not at all, with detrimental effects for their life. The
      identification of individual symptom patterns and the employment of new, more
      specific, drugs targeting the symptoms in question may lead to increased response
      rates, even in treatment resistant cases. We report a case of long standing
      depression which responded to reboxetine, a novel noradrenaline re-uptake
      inhibitor. (Int J Psych Clin Pract 1999; 3: 289-291). 

PMID- 24921235
TI  - A case study on the successful management of Cotard's syndrome in pregnancy: Case
      Reports.
AB  - Cotard's Syndrome is rare and no cases have been reported in pregnancy. We
      describe a case of a woman in the third trimester who attempted suicide by
      jumping out of a window, sustaining multiple fractures. Delivery of her baby by
      Caesarean section and orthopaedic intervention was necessary before
      electroconvulsive therapy (ECT) could be administered, resulting in a successful
      outcome for both mother and child. (Int J Psych Clin Pract 1999; 3: 293-295). 

PMID- 24921236
TI  - Topics in contemporary psychiatric practice: Consent and ethics.
AB  - Ethical issues in psychiatry are currently in a state of flux. As a profession
      the field of psychiatry has to clarify the ethical basis of treatment and
      research, by outlining the conceptual issues and empirical findings related to
      the ethics of human experimentation. Psychiatrists must endeavour to anticipate
      the ethical problems of the future and to respond conscientiously to the next
      generation of ethical dilemmas, that will inevitably arise with advances in
      science. Indeed, such considerations are already an aspect of genetic research.
      The ethics embracing research in humans are broadly governed by a number of basic
      principles: respect for people, beneficence, justice, and the ideal of informed
      consent. 

PMID- 24921238
TI  - Involving decision-makers in the research process: Challenges of implementing the
      accountability for reasonableness approach to priority setting at the district
      level in Tanzania.
AB  - The past two decades have seen a growing call for researchers, policy-makers and
      health care providers to collaborate in efforts to bridge the gaps between
      research, policy and practice. However, there has been a little attention focused
      on documenting the challenges of dealing with decision-makers in the course of
      implementing a research project. This paper highlights a collaborative research
      project aiming to implement the accountability for reasonableness (AFR) approach
      to priority setting in accordance with the Response to Accountable Priority
      Setting for Trust in Health Systems (REACT) project in Tanzania. Specifically,
      the paper examines the challenges of dealing with decision-makers during the
      project-implementation process and shows how the researchers dealt with the
      decision-makers to facilitate the implementation of the REACT project. Key
      informant interviews were conducted with the Council Health Management Team
      (CHMT), local government officials and other stakeholders, using a semi
      structured interview guide. Minutes of the Action Research Team and CHMT were
      analysed. Additionally, project-implementation reports were analysed and group
      priority-setting processes in the district were observed. The findings show that
      the characteristics of the REACT research project, the novelty of some aspects of
      the AFR approach, such as publicity and appeals, the Action Research methodology
      used to implement the project and the traditional cultural contexts within which
      the project was implemented, created challenges for both researchers and decision
      makers, which consequently slowed down the implementation of the REACT project.
      While collaboration between researchers and decision-makers is important in
      bridging gaps between research and practice, it is imperative to understand the
      challenges of dealing with decision-makers in the course of implementing a
      collaborative research project. Such analyses are crucial in designing proper
      strategies for improved communication and for the utilisation of research
      projects over time. 

PMID- 24921239
TI  - Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients
      with distinct neuropsychiatric symptoms: findings from a pilot study.
AB  - BACKGROUND: Clusterin protein in plasma has been found to differentiate between
      people with and without cognitive changes. However, these findings are not
      conclusive, despite the clusterin gene variations repeatedly being linked to
      increased risk for dementia, in particular Alzheimer's disease (AD). METHOD: We
      analysed the level of clusterin in platelet and plasma in 25 subjects with a
      clinical diagnosis of AD and 26 subjects with no cognitive impairment. RESULTS:
      In the current study, we report that the levels of both plasma and platelet
      clusterin are similar between AD and cognitively intact individuals. Clusterin
      plasma and platelet levels, as well as the plasma/platelet clusterin ratio, were
      not affected by age, gender, cognitive impairment and/or overt behavioural
      symptomatology, including presence of hallucinations and delusions, as well as
      depression. However, the plasma/platelet clusterin ratio was positively
      associated in with the Neuropsychiatric Inventory measures of agitation, apathy,
      irritability and motor aberrant behaviour in AD subjects. CONCLUSION: Previous
      inconsistencies in reported blood clusterin levels may be a result of underlying
      non-cognitive symptoms in people with AD. Our findings need now to be replicated
      in larger group of dementia subjects.

PMID- 24921240
TI  - Warts (non-genital).
AB  - INTRODUCTION: Warts are caused by the human papillomavirus (HPV), of which there
      are over 100 types. HPV probably infects the skin via areas of minimal trauma.
      Risk factors include use of communal showers, occupational handling of meat, and
      immunosuppression. In immunocompetent people, warts are harmless and resolve as a
      result of natural immunity within months or years. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      question: What are the effects of treatments for warts (non-genital)? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to October 2013 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 17 studies that met our inclusion criteria. We performed a
      GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In
      this systematic, review we present information relating to the effectiveness and
      safety of the following interventions: intralesional bleomycin; intralesional
      candida antigen; contact immunotherapy; cryotherapy; duct tape occlusion;
      photodynamic treatment; pulsed dye laser; surgical procedures; and topical
      salicylic acid.

PMID- 24921241
TI  - A new role for Rab GTPases during early mitotic stages.
AB  - A recent study revealed new roles for the Rab11 GTPase during mitosis. Rab11 is
      involved in recycling endosome localization to mitotic spindle poles via dynein
      mediated transport. This process is in contrast to Golgi membranes, which
      disperse in mitosis and do not appear to directly contribute to mitotic
      functions. Rab11-depletion prevents recycling endosome organization at spindle
      poles, delays mitotic progression, and disrupts spindle pole protein recruitment,
      astral microtubule organization, and mitotic spindle orientation. However, Rab11
      is not the only endocytic and/or trafficking protein that regulates mitotic
      progression. Clathrin and two small GTPases (Rab6A', Rab5) play key roles in
      spindle organization and function. In this commentary, we discuss the roles of
      all these canonical endocytic and membrane trafficking proteins during mitosis
      and speculate on possible cross-communication between them and their molecular
      pathways that ensure faithful progression through mitosis. 

PMID- 24921244
TI  - Social sciences research on infectious diseases of poverty: too little and too
      late?

PMID- 24921243
TI  - Explaining the host-finding behavior of blood-sucking insects: computerized
      simulation of the effects of habitat geometry on tsetse fly movement.
AB  - BACKGROUND: Male and female tsetse flies feed exclusively on vertebrate blood.
      While doing so they can transmit the diseases of sleeping sickness in humans and
      nagana in domestic stock. Knowledge of the host-orientated behavior of tsetse is
      important in designing bait methods of sampling and controlling the flies, and in
      understanding the epidemiology of the diseases. For this we must explain several
      puzzling distinctions in the behavior of the different sexes and species of
      tsetse. For example, why is it that the species occupying savannahs, unlike those
      of riverine habitats, appear strongly responsive to odor, rely mainly on large
      hosts, are repelled by humans, and are often shy of alighting on baits?
      METHODOLOGY/PRINCIPAL FINDINGS: A deterministic model that simulated fly mobility
      and host-finding success suggested that the behavioral distinctions between
      riverine, savannah and forest tsetse are due largely to habitat size and shape,
      and the extent to which dense bushes limit occupiable space within the habitats.
      These factors seemed effective primarily because they affect the daily
      displacement of tsetse, reducing it by up to ~70%. Sex differences in behavior
      are explicable by females being larger and more mobile than males.
      CONCLUSION/SIGNIFICANCE: Habitat geometry and fly size provide a framework that
      can unify much of the behavior of all sexes and species of tsetse everywhere. The
      general expectation is that relatively immobile insects in restricted habitats
      tend to be less responsive to host odors and more catholic in their diet. This
      has profound implications for the optimization of bait technology for tsetse,
      mosquitoes, black flies and tabanids, and for the epidemiology of the diseases
      they transmit.

PMID- 24921242
TI  - Cellular microRNAs and picornaviral infections.
AB  - microRNAs (miRNAs) are a subtype of short, endogenous, and non-coding RNAs, which
      post-transcriptionally regulate gene expression. The miRNA-mediated gene
      silencing mechanism is involved in a wide spectrum of biological processes, such
      as cellular proliferation, differentiation, and immune responses. Picornaviridae
      is a large family of RNA viruses, which includes a number of causative agents of
      many human and animal diseases viz., poliovirus, foot-and-mouth disease virus
      (FMDV), and coxsackievirus B3 (CVB3). Accumulated evidences have demonstrated
      that replication of picornaviruses can be regulated by miRNAs and picornaviral
      infections can alter the expression of cellular miRNAs. Herein, we outline the
      intricate interactions between miRNAs and picornaviral infections. 

PMID- 24921245
TI  - Sorting signal targeting mRNA into hepatic extracellular vesicles.
AB  - Intercellular communication mediated by extracellular vesicles has proved to play
      an important role in normal and pathological scenarios. However not too much
      information about the sorting mechanisms involved in loading the vesicles is
      available. Recently, our group has characterized the mRNA content of vesicles
      released by hepatic cellular systems, showing that a set of transcripts was
      particularly enriched in the vesicles in comparison with their intracellular
      abundance. In the current work, based on in silico bioinformatics tools, we have
      mapped a novel sequence of 12 nucleotides C[TA]G[GC][AGT]G[CT]C[AT]GG[GA], which
      is significantly enriched in the set of mRNAs that accumulate in extracellular
      vesicles. By including a 3'-UTR containing this sequence in a luciferase mRNA
      reporter, we have shown that in a hepatic cellular system this reporter mRNA was
      incorporated into extracellular vesicles. This study identifies a sorting signal
      in mRNAs that is involved in their enrichment in EVs, within a hepatic non
      tumoral cellular model. 

PMID- 24921246
TI  - Mapping B-cell epitopes for the peroxidoxin of Leishmania (Viannia) braziliensis
      and its potential for the clinical diagnosis of tegumentary and visceral
      leishmaniasis.
AB  - The search toward the establishment of novel serological tests for the diagnosis
      of leishmaniasis and proper differential diagnosis may represent one alternative
      to the invasive parasitological methods currently used to identify infected
      individuals. In the present work, we investigated the potential use of
      recombinant peroxidoxin (rPeroxidoxin) of Leishmania (Viannia) braziliensis as a
      potential antigen for the immunodiagnosis of human tegumentary (TL) and visceral
      leishmaniasis (VL) and canine visceral leishmaniasis (CVL). Linear B-cell epitope
      mapping was performed to identify polymorphic epitopes when comparing orthologous
      sequences present in Trypanosoma cruzi, the agent for Chagas disease (CD), and
      the Homo sapiens and Canis familiaris hosts. The serological assay (ELISA)
      demonstrated that TL, VL and CVL individuals showed high levels of antibodies
      against rPeroxidoxin, allowing identification of infected ones with considerable
      sensitivity and great ability to discriminate (specificity) between non-infected
      and CD individuals (98.46% and 100%; 98.18% and 95.71%; 95.79% and 100%,
      respectively). An rPeroxidoxin ELISA also showed a greater ability to
      discriminate between vaccinated and infected animals, which is an important
      requirement for the public campaign control of CVL. A depletion ELISA assay using
      soluble peptides of this B-cell epitope confirmed the recognition of these sites
      only by Leishmania-infected individuals. Moreover, this work identifies two
      antigenic polymorphic linear B-cell epitopes of L. braziliensis. Specific
      recognition of TL and VL patients was confirmed by significantly decreased IgG
      reactivity against rPeroxidoxin after depletion of peptide-1- and peptide-2
      specific antibodies (peptide 1: reduced by 32%, 42% and 5% for CL, ML and VL,
      respectively; peptide-2: reduced by 24%, 22% and 13% for CL, ML and VL,
      respectively) and only peptide-2 for CVL (reduced 9%). Overall, rPeroxidoxin may
      be a potential antigen for the immunodiagnosis of TL, VL or CVL, as it has a
      higher agreement with parasitological assays and is better than other reference
      tests that use soluble Leishmania antigens for diagnosing CVL in Brazil (EIE-LVC,
      Bio-manguinhos, FIOCRUZ). 

PMID- 24921247
TI  - Sensitive simultaneous detection of seven sexually transmitted agents in semen by
      multiplex-PCR and of HPV by single PCR.
AB  - Sexually transmitted diseases (STDs) may impair sperm parameters and functions
      thereby promoting male infertility. To date limited molecular studies were
      conducted to evaluate the frequency and type of such infections in semen Thus, we
      aimed at conceiving and validating a multiplex PCR (M-PCR) assay for the
      simultaneous detection of the following STD pathogens in semen: Chlamydia
      trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis,
      Herpes virus simplex (HSV) -1 and -2, and Treponema pallidum; We also
      investigated the potential usefulness of this M-PCR assay in screening programs
      for semen pathogens. In addition, we aimed: to detect human Papillomavirus (HPV)
      and genotypes by single PCR (sPCR) in the same semen samples; to determine the
      prevalence of the seven STDs, HPV and co-infections; to assess the possibility
      that these infections affect semen parameters and thus fertility. The overall
      validation parameters of M-PCR were extremely high including agreement (99.2%),
      sensitivity (100.00%), specificity (99.70%), positive (96.40%) and negative
      predictive values (100.00%) and accuracy (99.80%). The prevalence of STDs was
      very high (55.3%). Furthermore, associations were observed between STDs and
      changes in semen parameters, highlighting the importance of STD detection in
      semen. Thus, this M-PCR assay has great potential for application in semen
      screening programs for pathogens in infertility and STD clinics and in sperm
      banks. 

PMID- 24921248
TI  - MicroRNA profiles discriminate among colon cancer metastasis.
AB  - MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer
      and other diseases. Their high tissue specificity and critical role in
      oncogenesis provide new biomarkers for the diagnosis and classification of cancer
      as well as predicting patients' outcomes. MicroRNAs signatures have been
      identified for many human tumors, including colorectal cancer (CRC). In most
      cases, metastatic disease is difficult to predict and to prevent with adequate
      therapies. The aim of our study was to identify a microRNA signature for
      metastatic CRC that could predict and differentiate metastatic target organ
      localization. Normal and cancer tissues of three different groups of CRC patients
      were analyzed. RNA microarray and TaqMan Array analysis were performed on 66
      Italian patients with or without lymph nodes and/or liver recurrences. Data
      obtained with the two assays were analyzed separately and then intersected to
      identify a primary CRC metastatic signature. Five differentially expressed
      microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a
      second group of 16 American metastatic patients. In situ hybridization was
      performed on the 16 American patients as well as on three distinct commercial
      tissues microarray (TMA) containing normal adjacent colon, the primary
      adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93,
      and -103 upregulation together with hsa-miR-566 downregulation defined the CRC
      metastatic signature, while in situ hybridization data identified a lymphonodal
      invasion profile. We provided the first microRNAs signature that could
      discriminate between colorectal recurrences to lymph nodes and liver and between
      colorectal liver metastasis and primary hepatic tumor. 

PMID- 24921249
TI  - A unifying mechanistic model of selective attention in spiking neurons.
AB  - Visuospatial attention produces myriad effects on the activity and selectivity of
      cortical neurons. Spiking neuron models capable of reproducing a wide variety of
      these effects remain elusive. We present a model called the Attentional Routing
      Circuit (ARC) that provides a mechanistic description of selective attentional
      processing in cortex. The model is described mathematically and implemented at
      the level of individual spiking neurons, with the computations for performing
      selective attentional processing being mapped to specific neuron types and
      laminar circuitry. The model is used to simulate three studies of attention in
      macaque, and is shown to quantitatively match several observed forms of
      attentional modulation. Specifically, ARC demonstrates that with shifts of
      spatial attention, neurons may exhibit shifting and shrinking of receptive
      fields; increases in responses without changes in selectivity for non-spatial
      features (i.e. response gain), and; that the effect on contrast-response
      functions is better explained as a response-gain effect than as contrast-gain.
      Unlike past models, ARC embodies a single mechanism that unifies the above forms
      of attentional modulation, is consistent with a wide array of available data, and
      makes several specific and quantifiable predictions. 

PMID- 24921251
TI  - In vitro biocompatibility and endothelialization of novel magnesium-rare Earth
      alloys for improved stent applications.
AB  - Magnesium (Mg) based alloys are the most advanced cardiovascular stent materials.
      This new generation of stent scaffold is currently under clinical evaluation with
      encouraging outcomes. All these Mg alloys contain a certain amount of rare earth
      (RE) elements though the exact composition is not yet disclosed. RE alloying can
      usually enhance the mechanical strength of different metal alloys but their
      toxicity might be an issue for medical applications. It is still unclear how RE
      elements will affect the magnesium (Mg) alloys intended for stent materials as a
      whole. In this study, we evaluated MgZnCaY-1RE, MgZnCaY-2RE, MgYZr-1RE, and
      MgZnYZr-1RE alloys for cardiovascular stents applications regarding their
      mechanical strength, corrosion resistance, hemolysis, platelet
      adhesion/activation, and endothelial biocompatibility. The mechanical properties
      of all alloys were significantly improved. Potentiodynamic polarization showed
      that the corrosion resistance of four alloys was at least 3-10 times higher than
      that of pure Mg control. Hemolysis test revealed that all the materials were non
      hemolytic while little to moderate platelet adhesion was found on all materials
      surface. No significant cytotoxicity was observed in human aorta endothelial
      cells cultured with magnesium alloy extract solution for up to seven days. Direct
      endothelialization test showed that all the alloys possess significantly better
      capability to sustain endothelial cell attachment and growth. The results
      demonstrated the promising potential of these alloys for stent material
      applications in the future. 

PMID- 24921250
TI  - Early back-to-Africa migration into the Horn of Africa.
AB  - Genetic studies have identified substantial non-African admixture in the Horn of
      Africa (HOA). In the most recent genomic studies, this non-African ancestry has
      been attributed to admixture with Middle Eastern populations during the last few
      thousand years. However, mitochondrial and Y chromosome data are suggestive of
      earlier episodes of admixture. To investigate this further, we generated new
      genome-wide SNP data for a Yemeni population sample and merged these new data
      with published genome-wide genetic data from the HOA and a broad selection of
      surrounding populations. We used multidimensional scaling and ADMIXTURE methods
      in an exploratory data analysis to develop hypotheses on admixture and population
      structure in HOA populations. These analyses suggested that there might be
      distinct, differentiated African and non-African ancestries in the HOA. After
      partitioning the SNP data into African and non-African origin chromosome
      segments, we found support for a distinct African (Ethiopic) ancestry and a
      distinct non-African (Ethio-Somali) ancestry in HOA populations. The African
      Ethiopic ancestry is tightly restricted to HOA populations and likely represents
      an autochthonous HOA population. The non-African ancestry in the HOA, which is
      primarily attributed to a novel Ethio-Somali inferred ancestry component, is
      significantly differentiated from all neighboring non-African ancestries in North
      Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed
      HOA ethnic groups, shows little inter-individual variance within these ethnic
      groups, is estimated to have diverged from all other non-African ancestries by at
      least 23 ka, and does not carry the unique Arabian lactase persistence allele
      that arose about 4 ka. Taking into account published mitochondrial, Y chromosome,
      paleoclimate, and archaeological data, we find that the time of the Ethio-Somali
      back-to-Africa migration is most likely pre-agricultural. 

PMID- 24921252
TI  - Daily rhythmicity of clock gene transcripts in atlantic cod fast skeletal muscle.
AB  - The classical notion of a centralized clock that governs circadian rhythmicity
      has been challenged with the discovery of peripheral oscillators that enable
      organisms to cope with daily changes in their environment. The present study
      aimed to identify the molecular clock components in Atlantic cod (Gadus morhua)
      and to investigate their daily gene expression in fast skeletal muscle. Atlantic
      cod clock genes were closely related to their orthologs in teleosts and
      tetrapods. Synteny was conserved to varying degrees in the majority of the 18
      clock genes examined. In particular, aryl hydrocarbon receptor nuclear
      translocator-like 2 (arntl2), RAR-related orphan receptor A (rora) and timeless
      (tim) displayed high degrees of conservation. Expression profiling during the
      early ontogenesis revealed that some transcripts were maternally transferred,
      namely arntl2, cryptochrome 1b and 2 (cry1b and cry2), and period 2a and 2b
      (per2a and per2b). Most clock genes were ubiquitously expressed in various
      tissues, suggesting the possible existence of multiple peripheral clock systems
      in Atlantic cod. In particular, they were all detected in fast skeletal muscle,
      with the exception of neuronal PAS (Per-Arnt-Single-minded) domain-containing
      protein (npas1) and rora. Rhythmicity analysis revealed 8 clock genes with daily
      rhythmic expression, namely arntl2, circadian locomotor output cycles kaput
      (clock), npas2, cry2, cry3 per2a, nuclear receptor subfamily 1, group D, member 1
      (nr1d1), and nr1d2a. Transcript levels of the myogenic genes myogenic factor 5
      (myf5) and muscleblind-like 1 (mbnl1) strongly correlated with clock gene
      expression. This is the first study to unravel the molecular components of
      peripheral clocks in Atlantic cod. Taken together, our data suggest that the
      putative clock system in fast skeletal muscle of Atlantic cod has regulatory
      implications on muscle physiology, particularly in the expression of genes
      related to myogenesis. 

PMID- 24921253
TI  - Exploring the relationship between access to water, sanitation and hygiene and
      soil-transmitted helminth infection: a demonstration of two recursive
      partitioning tools.
AB  - BACKGROUND: Soil-transmitted helminths (STH) - a class of parasites that affect
      billions of people - can be mitigated using mass drug administration, though
      reinfection following treatment occurs within a few months. Improvements to
      water, sanitation and hygiene (WASH) likely provide sustained benefit, but few
      rigorous studies have evaluated the specific WASH components most influential in
      reducing infection. There is a need for alternative analytic approaches to help
      identify, characterize and further refine the WASH components that are most
      important to STH reinfection. Traditional epidemiological approaches are not well
      suited for assessing the complex and highly correlated relationships commonly
      seen in WASH. METHODOLOGY: We introduce two recursive partitioning approaches:
      classification and regression trees (C&RT) and conditional inference trees (CIT),
      which can be used to identify complex interactions between WASH indicators and
      identify sub-populations that may be susceptible to STH reinfection. We
      illustrate the advantages and disadvantages of these approaches utilizing school-
      and household-level WASH indicators gathered as part of a school-based randomized
      control trial in Kenya that measured STH reinfection of pupils 10 months
      following deworming treatment. PRINCIPAL FINDINGS: C&RT and CIT analyses resulted
      in strikingly different decision trees. C&RT may be the preferred approach if
      interest lies in using WASH indicators to classify individuals or communities as
      STH infected or uninfected, whereas CIT is most appropriate for identifying WASH
      indicators that may be causally associated with STH infection. Both tools are
      well-suited for identifying complex interactions among WASH indicators.
      CONCLUSIONS/SIGNIFICANCE: C&RT and CIT are two analytic approaches that may offer
      valuable insight regarding the identification, selection and refinement of WASH
      indicators and their interactions with regards to STH control programs; however,
      they represent solutions to two distinct research questions and careful
      consideration should be made before deciding which approach is most appropriate.

PMID- 24921254
TI  - Strategy switching in the stabilization of unstable dynamics.
AB  - In order to understand mechanisms of strategy switching in the stabilization of
      unstable dynamics, this work investigates how human subjects learn to become
      skilled users of an underactuated bimanual tool in an unstable environment. The
      tool, which consists of a mass and two hand-held non-linear springs, is affected
      by a saddle-like force-field. The non-linearity of the springs allows the users
      to determine size and orientation of the tool stiffness ellipse, by using
      different patterns of bimanual coordination: minimal stiffness occurs when the
      two spring terminals are aligned and stiffness size grows by stretching them
      apart. Tool parameters were set such that minimal stiffness is insufficient to
      provide stable equilibrium whereas asymptotic stability can be achieved with
      sufficient stretching, although at the expense of greater effort. As a
      consequence, tool users have two possible strategies for stabilizing the mass in
      different regions of the workspace: 1) high stiffness feedforward strategy,
      aiming at asymptotic stability and 2) low stiffness positional feedback strategy
      aiming at bounded stability. The tool was simulated by a bimanual haptic robot
      with direct torque control of the motors. In a previous study we analyzed the
      behavior of naive users and we found that they spontaneously clustered into two
      groups of approximately equal size. In this study we trained subjects to become
      expert users of both strategies in a discrete reaching task. Then we tested
      generalization capabilities and mechanism of strategy-switching by means of
      stabilization tasks which consist of tracking moving targets in the workspace.
      The uniqueness of the experimental setup is that it addresses the general problem
      of strategy-switching in an unstable environment, suggesting that complex
      behaviors cannot be explained in terms of a global optimization criterion but
      rather require the ability to switch between different sub-optimal mechanisms. 

PMID- 24921255
TI  - A new online computational biology curriculum.
AB  - A recent proliferation of Massive Open Online Courses (MOOCs) and other web-based
      educational resources has greatly increased the potential for effective self
      study in many fields. This article introduces a catalog of several hundred free
      video courses of potential interest to those wishing to expand their knowledge of
      bioinformatics and computational biology. The courses are organized into eleven
      subject areas modeled on university departments and are accompanied by commentary
      and career advice. 

PMID- 24921256
TI  - Investigation of pathogenic genes in peri-implantitis from implant clustering
      failure patients: a whole-exome sequencing pilot study.
AB  - Peri-implantitis is a frequently occurring gum disease linked to multi-factorial
      traits with various environmental and genetic causalities and no known concrete
      pathogenesis. The varying severity of peri-implantitis among patients with
      relatively similar environments suggests a genetic aspect which needs to be
      investigated to understand and regulate the pathogenesis of the disease. Six
      unrelated individuals with multiple clusterization implant failure due to severe
      peri-implantitis were chosen for this study. These six individuals had relatively
      healthy lifestyles, with minimal environmental causalities affecting peri
      implantitis. Research was undertaken to investigate pathogenic genes in peri
      implantitis albeit with a small number of subjects and incomplete elimination of
      environmental causalities. Whole-exome sequencing was performed on collected
      saliva samples via self DNA collection kit. Common variants with minor allele
      frequencies (MAF) > = 0.05 from all control datasets were eliminated and variants
      having high and moderate impact and loss of function were used for comparison.
      Gene set enrichment analysis was performed to reveal functional groups associated
      with the genetic variants. 2,022 genes were left after filtering against dbSNP,
      the 1000 Genomes East Asian population, and healthy Korean randomized subsample
      data (GSK project). 175 (p-value <0.05) out of 927 gene sets were obtained via
      GSEA (DAVID). The top 10 was chosen (p-value <0.05) from cluster enrichment
      showing significance of cytoskeleton, cell adhesion, and metal ion binding.
      Network analysis was applied to find relationships between functional clusters.
      Among the functional groups, ion metal binding was located in the center of all
      clusters, indicating dysfunction of regulation in metal ion concentration might
      affect cell morphology or cell adhesion, resulting in implant failure. This
      result may demonstrate the feasibility of and provide pilot data for a larger
      research project aimed at discovering biomarkers for early diagnosis of peri
      implantitis. 

PMID- 24921257
TI  - CellFIT: a cellular force-inference toolkit using curvilinear cell boundaries.
AB  - Mechanical forces play a key role in a wide range of biological processes, from
      embryogenesis to cancer metastasis, and there is considerable interest in the
      intuitive question, "Can cellular forces be inferred from cell shapes?" Although
      several groups have posited affirmative answers to this stimulating question,
      nagging issues remained regarding equation structure, solution uniqueness and
      noise sensitivity. Here we show that the mechanical and mathematical factors
      behind these issues can be resolved by using curved cell edges rather than
      straight ones. We present a new package of force-inference equations and
      assessment tools and denote this new package CellFIT, the Cellular Force
      Inference Toolkit. In this approach, cells in an image are segmented and
      equilibrium equations are constructed for each triple junction based solely on
      edge tensions and the limiting angles at which edges approach each junction. The
      resulting system of tension equations is generally overdetermined. As a result,
      solutions can be obtained even when a modest number of edges need to be removed
      from the analysis due to short length, poor definition, image clarity or other
      factors. Solving these equations yields a set of relative edge tensions whose
      scaling must be determined from data external to the image. In cases where
      intracellular pressures are also of interest, Laplace equations are constructed
      to relate the edge tensions, curvatures and cellular pressure differences. That
      system is also generally overdetermined and its solution yields a set of
      pressures whose offset requires reference to the surrounding medium, an open
      wound, or information external to the image. We show that condition numbers,
      residual analyses and standard errors can provide confidence information about
      the inferred forces and pressures. Application of CellFIT to several live and
      fixed biological tissues reveals considerable force variability within a cell
      population, significant differences between populations and elevated tensions
      along heterotypic boundaries. 

PMID- 24921258
TI  - Monocarboxylate transporters as targets and mediators in cancer therapy response.
AB  - Monocarboxylate transporters (MCTs) belong to a family of transporters, encoded
      by the SLC16 gene family, which is presently composed by 14 members, but only
      MCT1 to 4 have been biochemically characterized. They have important functions in
      healthy tissues, being involved in the transmembrane transport of lactic acid and
      other monocarboxylic acids in human cells. One of the recently recognized
      hallmarks of cancer is altered metabolism, with high rates of glucose consumption
      and consequent lactate production. To maintain this metabolic phenotype, cancer
      cells upregulate a series of plasma membrane proteins, including MCTs. MCT1 and
      MCT4, in particular, play a dual role in the maintenance of the metabolic
      phenotype of tumour cells. On one hand, they facilitate the efflux of lactate
      and, on the other hand, they contribute to the preservation of the intracellular
      pH, by co-transporting a proton. Thus, MCTs are attractive targets in cancer
      therapy, especially in cancers with a hyper-glycolytic and acid-resistant
      phenotype. Recent evidence demonstrates that MCTs are involved in cancer cell
      uptake of chemotherapeutic agents, including 3-bromopyruvate. In this way MCTs
      can act as "Trojan horses", as their elevated expression in cancer cells can
      mediate the entry of this chemotherapeutic agent into the cells and selectively
      kill cancer cells. As a result, MCTs will be mediators of chemotherapeutic
      response, and their expression can be used as a molecular marker to predict
      response to chemotherapy.

PMID- 24921260
TI  - Suppression of electron leakage by inserting a thin undoped InGaN layer prior to
      electron blocking layer in InGaN-based blue-violet laser diodes.
AB  - InGaN-based blue-violet laser diodes (LDs) suffer from electron leakage into the
      p-type regions, which could be only partially alleviated by employing the
      electron blocking layer (EBL). Here, a thin undoped InGaN interlayer prior to EBL
      is proposed to create an additional forbidden energy range above the natural
      conduction band edge, which further suppresses the electron leakage and thus
      improve the characteristics of LDs. Numerical device simulations reveal that when
      the proper composition and thickness of InGaN interlayer are chosen, the electron
      leakage could be efficiently eliminated without inducing any severe accumulation
      of electrons at the interlayer, resulting in a maximum output power of the
      device. 

PMID- 24921259
TI  - Renal function in Ghanaian HIV-infected patients on highly active antiretroviral
      therapy: a case-control study.
AB  - BACKGROUND: HAART is anticipated to result in an increase in long-term survival,
      but may present with the development of associated complications. The aim of this
      study was to assess the renal function of HIV-infected patients on antiretroviral
      therapy. METHODS: A case-control study (January to May 2013) conducted at the
      Suntreso Government Hospital, Kumasi, Ghana. A total of 163 HIV-infected patients
      (mean age 39.9+/-10.22) were studied, of which 111 were on HAART (HIV-HAART) and
      52 were not (HIV-Controls). Serum urea, creatinine, potassium, sodium, chloride
      and CD4 counts were measured with the determination of eGFR (CKD-EPI and MDRD).
      Data was analysed using GraphPad Prism. The Chi-square, t-test, one-way ANOVA and
      Spearman's correlation were used. P values <0.05 were considered significant.
      RESULTS: Mean CD4 count of HIV-Controls was higher than that of HIV-HAART but was
      not significant (p = 0.304). But for sodium levels which were higher in HIV
      Controls (p = 0.0284), urea (p = 0.1209), creatinine (p = 0.7155), potassium (p =
      0.454) and chloride (p = 0.6282) levels did not differ significantly between both
      groups. All serum biochemical parameters did not differ significantly,
      irrespective of duration on therapy and CD4 counts. Based on regimen, sodium,
      chloride, urea and creatinine did not differ significantly between TDF, EVF and
      NVP-based therapies. Prevalence of CKD (eGFR <60 ml/min/1.73 m2) in the total
      population was 9.9% and 3.7% with the MDRD and EPI-CKD equations respectively.
      CONCLUSIONS: Renal insufficiency remains prevalent in HIV patients. Changes in
      renal function occur in HIV infection and over the course of HAART but the
      difference at either stage is not significant. This suggests the role of HIV
      infection, HAART and the presence of traditional risk factors but not HAART in
      itself, in renal dysfunction. We however recommend a close monitoring of patients
      before and during HAART, to aid in evaluating drug combinations and implement
      dose modifications when necessary.

PMID- 24921261
TI  - Multi-spectral plasmon induced transparency via in-plane dipole and dual
      quadrupole coupling.
AB  - We experimentally demonstrated an approach based on dipole and dual-quadrupole
      coupling to construct a planar metamaterial supporting multi-spectral plasmon
      induced transparency. The structure consists of two short silver wires (dipole)
      and two long silver wires (dual-quadrupole). The in-plane coupling between the
      dipole and the dual-quadrupole leads to two transmission windows even in the
      absorbance linewidth of the dipole. This phenomenon is well described and
      understood by numerical analyses and a classical oscillator model. 

PMID- 24921262
TI  - Recovery of wavefront from multi-shear interferograms with different tilts.
AB  - An improved multi-shear algorithm is proposed to reconstruct a two-dimensional
      wavefront from multiple phase differences measured by lateral shearing
      interferograms with different tilts. The effects of the tilt errors in the
      wavefront are analyzed and a compensation method is developed. Unbiased
      estimators are added to Fourier coefficients of the phase differences to
      eliminate the tilt errors adaptively. The algorithm is immune to the tilt errors
      and the wavefront under test can be recovered exactly. Computer simulation and
      optical test demonstrated that the proposed algorithm has higher recovery
      accuracy than the existing multi-shear algorithms. 

PMID- 24921263
TI  - Tunable and switchable multi-wavelength dissipative soliton generation in a
      graphene oxide mode-locked Yb-doped fiber laser.
AB  - We report the generation of tunable single-, switchable and tunable dual-, and
      stable triple-wavelength dissipative solitons (DSs) in an all-normal-dispersion
      mode-locked Yb-doped fiber laser based on a graphene-oxide saturable absorber
      (GOSA) without additional components (such as optical filter, or fiber grating).
      The tunable single-wavelength DS have a wide wavelength-tunable range of 16.4 nm.
      The dual-wavelength DSs not only have a wavelength-tunable range (about 10 nm)
      but also have variable wavelength spacing (3.8-13.8 nm). The formation dynamics
      of the triple-wavelength DSs was also investigated experimentally. The different
      operations of tunable single-, switchable and tunable dual-, and stable triple
      wavelength DSs depend on the strength of the cavity birefringence. The simple,
      compact all-fiber DS laser with lasing wavelength tunability and flexibility can
      meet great potential for applications. 

PMID- 24921264
TI  - An electrically tunable imaging system with separable focus and zoom functions
      using composite liquid crystal lenses.
AB  - We demonstrated an electrically tunable optical image system with separable focus
      function and zoom function based on three tunable focusing composite liquid
      crystal (LC) lenses. One LC lens in charge of the focus function helps to
      maintain the formed image at the same position and the other two LC lenses in
      charge of zoom function assist to continuously form an image at image sensor with
      tunable magnification of image size. The detail optical mechanism is investigated
      and the concept is demonstrated experimentally. The magnifications of the images
      can be switched continuously for the target in a range between 10 cm and 100 cm.
      The optical zoom ratio of this system maintains a constant~6.5:1 independent of
      the object distance. This study provides not only a guideline to design the image
      system with an electrically optical zoom, but also provide an experimental
      process to show how to operate the tunable focusing lenses in such an image
      system. 

PMID- 24921265
TI  - Surface plasmon enhanced photoluminescence of ZnO nanorods by capping reduced
      graphene oxide sheets.
AB  - A hybrid structure of reduced graphene oxide (rGO) sheets/ZnO nanorods was
      prepared and its photoluminescence intensity ratio between the UV and defect
      emission was enhanced up to 14 times. By controlling the reduction degree of rGO
      on the surface of ZnO nanorods, the UV emission was tuned with the introduction
      of localized surface plasmons resonance of rGO sheets. The suppression of the
      defect emission was ascribed to the charge transfer and decreased with the
      distance between the rGO and ZnO nanorods. 

PMID- 24921266
TI  - A 1.33 um picosecond pulse generator based on semiconductor disk mode-locked
      laser and bismuth fiber amplifier.
AB  - We demonstrate that a combination of ultrafast wafer bonded semiconductor disk
      laser and a bismuth-doped fiber amplifier provides an attractive design for high
      power 1.33 um tandem hybrid systems. Over 0.5 W of average output power was
      achieved at a repetition rate of 827 MHz that corresponds to a pulse energy of
      0.62 nJ.

PMID- 24921267
TI  - 4 * 160-Gbit/s multi-channel regeneration in a single fiber.
AB  - Simultaneous regeneration of four high-speed (160 Gbit/s) wavelength-division
      multiplexed (WDM) and polarization-division multiplexed (PDM) signals in a single
      highly nonlinear fiber (HNLF) is demonstrated. The regeneration operation is
      based on four-wave mixing in HNLF, where the degraded data signals are applied as
      the pump. As a result, the noise on both '0' and '1' levels can be suppressed
      simultaneously in our scheme. The stimulated Brillouin scattering (SBS) from the
      continuous wave (CW) is suppressed by cross-phase modulation (XPM) from the data
      pump, relieving the requirement of external phase modulation of the CW light.
      Mitigation of the inter-channel nonlinearities is achieved mainly through an
      inter-channel 0.5 bit slot time delay. Bidirectional propagation is also applied
      to relieve the inter-channel four-wave mixing. The multi-channel regeneration
      performance is validated by bit-error rate (BER) measurements. The receiver
      powers at the BER of 10(-9) are improved by 1.9 dB, 1.8 dB, 1.6 dB and 1.5 dB for
      the four data channels, respectively.

PMID- 24921268
TI  - In vivo analysis of THz wave irradiation induced acute inflammatory response in
      skin by laser-scanning confocal microscopy.
AB  - The recent development of THz sources in a wide range of THz frequencies and
      power levels has led to greatly increased interest in potential biomedical
      applications such as cancer and burn wound diagnosis. However, despite its
      importance in realizing THz wave based applications, our knowledge of how THz
      wave irradiation can affect a live tissue at the cellular level is very limited.
      In this study, an acute inflammatory response caused by pulsed THz wave
      irradiation on the skin of a live mouse was analyzed at the cellular level using
      intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 MUs
      pulsewidth, 61.4 MUJ per pulse, 3Hz repetition), generated using compact FEL, was
      used to irradiate an anesthetized mouse's ear skin with an average power of 260
      mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation
      setup. In contrast to in vitro analysis using cultured cells at similar power
      levels of CW THz wave irradiation, no temperature change at the surface of the
      ear skin was observed when skin was examined with an IR camera. To monitor any
      potential inflammatory response, resident neutrophils in the same area of ear
      skin were repeatedly visualized before and after THz wave irradiation using a
      custom-built laser-scanning confocal microscopy system optimized for in vivo
      visualization. While non-irradiated control skin area showed no changes in the
      number of resident neutrophils, a massive recruitment of newly infiltrated
      neutrophils was observed in the THz wave irradiated skin area after 6 hours,
      which suggests an induction of acute inflammatory response by the pulsed THz wave
      irradiation on the skin via a non-thermal process.

PMID- 24921269
TI  - Yb-fiber-laser-pumped, high-repetition-rate picosecond optical parametric
      oscillator tunable in the ultraviolet.
AB  - We report a compact tunable 240-MHz picosecond source for the ultraviolet based
      on intra-cavity frequency doubling of a signal-resonant MgO:sPPLT optical
      parametric oscillator (OPO), synchronously pumped at 532 nm in the green by the
      second harmonic of a mode-locked Yb-fiber laser at 80-MHz repetition rate. By
      deploying a 30-mm-long multi-grating MgO:sPPLT crystal for the OPO and a 5-mm
      long BiB(3)O(6) crystal for internal doubling, we have generated tunable UV
      radiation across 317-340.5 nm, with up to 30 mW at 334.5 nm. The OPO also
      provides tunable visible signal in the red, across 634-681 nm, and mid-infrared
      idler radiation over 2429-3298 nm, with as maximum signal power of 800 mW at 642
      nm. The signal pulses have a temporal duration of 12 ps at 665 nm and exhibit
      high spatial beam quality with Gaussian profile. The signal power is recorded to
      be naturally stable with a fluctuation of 1.4% rms over 14 hours, while UV power
      degradation has been observed and studied.

PMID- 24921270
TI  - Mode add/drop multiplexers of LP02 and LP03 modes with two parallel combinative
      long-period fiber gratings.
AB  - Two parallel combinative long-period fiber gratings (LPFGs) can convert the
      fundamental core mode LP(01) in a single-mode fiber (SMF) into one desired higher
      order core mode LP(0m) in a few-mode fiber (FMF), in the process of which one
      specific cladding mode acts as a medium coupled from one fiber to another.
      Different LP(0m) modes can be obtained by controlling the grating period of LPFG
      in FMF to meet the phase matching condition. In this article we focus on the
      design and analyses of LP(02) and LP(03) mode add / drop multiplexers (MADMs).
      This device has some advantages of facile and good scalability, and particularly,
      of eliminating coupling interferences for the ahead multiplexed modes by the
      posterior MADMs or couplers. Furthermore, the conversion rate of mode power
      theoretically can approach as much as 98%and the 3dB bandwidth can reach 10nm or
      more.

PMID- 24921271
TI  - Pulsed Sagnac polarization-entangled photon source with a PPKTP crystal at
      telecom wavelength.
AB  - We demonstrate pulsed polarization-entangled photons generated from a
      periodically poled KTiOPO(4) (PPKTP) crystal in a Sagnac interferometer
      configuration at telecom wavelength. Since the group-velocity-matching (GVM)
      condition is satisfied, the intrinsic spectral purity of the photons is much
      higher than in the previous scheme at around 800 nm wavelength. The combination
      of a Sagnac interferometer and the GVM-PPKTP crystal makes our entangled source
      compact, stable, highly entangled, spectrally pure and ultra-bright. The photons
      were detected by two superconducting nanowire single photon detectors (SNSPDs)
      with detection efficiencies of 70% and 68% at dark counts of less than 1 kcps. We
      achieved fidelities of 0.981 +/- 0.0002 for |psi(-)> and 0.980 +/- 0.001 for
      |psi(+)> respectively. This GVM-PPKTP-Sagnac scheme is directly applicable to
      quantum communication experiments at telecom wavelength, especially in free
      space.

PMID- 24921272
TI  - High-repetition-rate Q-switched fiber laser with high quality topological
      insulator Bi2Se3 film.
AB  - We demonstrated a high-repetition-rate Q-switched fiber laser with topological
      insulator Bi2Se3 absorber. The absorber was made into a film structure by spin
      coating method using few-layer Bi2Se3 nano-platelets which had regular shape. The
      uniform film had a low saturable optical intensity of 11 MW/cm(2), which is the
      lowest saturable optical intensity in the saturable absorbers made by topological
      insulator till now. By inserting the absorber film into an Erbium-doped fiber
      laser, a high-repetition Q-switched laser with the repetition rates from 459 kHz
      to 940 kHz was achieved. The maximum output power was 22.35 mW with the shortest
      pulse duration of 1.9 MUs. To the best of our knowledge, both of the repetition
      rate and the output power were the highest values among the Q-switched fiber
      lasers with topological insulator absorber.

PMID- 24921273
TI  - Effect of plasmon-enhancement on photophysics in upconverting nanoparticles.
AB  - Surface plasmon polaritons (SPP) waves have been shown to significantly affect
      the near-field photophysical phenomenon. In particular, strong Coulombic
      interactions can enhance nearby non-linear optics and energy transfer process,
      while SPP waves also affect other photophysical processes like quenching observed
      in fluorescent and excitonic systems. Here, using different plasmonic substrates,
      we show the effect of plasmon-enhancement on quenching, phonon-assisted non
      radiative decay, weak Purcell effect or electromagnetic field enhancement, and
      energy transfer rates of upconverting doped-lanthanide nanoparticles. While the
      resonant plasmons enhance the local electromagnetic field and the rate of energy
      transfer leading to enhanced upconversion photoluminescence of infrared radiation
      to visible light, it can also increase the quenching and non-radiative decay
      rates of photoexcited electron-hole pairs leading to losses and lower efficiency.
      These results can guide the design of optimized substrate geometry for using
      surface plasmons to modulate the photophysics in other applications too. 

PMID- 24921274
TI  - 1.3-MUm InAs/GaAs quantum-dot lasers monolithically grown on Si substrates using
      InAlAs/GaAs dislocation filter layers.
AB  - We compare InAlAs/GaAs and InGaAs/GaAs strained-layer superlattices (SLSs) as
      dislocation filter layers for 1.3-MUm InAs/GaAs quantum-dot laser structures
      directly grown on Si substrates. InAlAs/GaAs SLSs are found to be more effective
      than InGaAs/GaAs SLSs in blocking the propagation of threading dislocations
      generated at the interface between the GaAs buffer layer and the Si substrate.
      Room-temperature lasing at ~1.27 MUm with a threshold current density of 194
      A/cm(2) and output power of ~77 mW has been demonstrated for broad-area lasers
      grown on Si substrates using InAlAs/GaAs dislocation filter layers.

PMID- 24921275
TI  - Sensitivity in reflectance attributed to phytoplankton cell size: forward and
      inverse modelling approaches.
AB  - Synoptic scale knowledge of the size structure of phytoplankton communities can
      offer insight in to primary ecosystem diversity and biogeochemical variability
      from operational to the decadal scales. Accordingly, obtaining estimates of size
      and other phytoplankton functional type descriptors within known confidence
      limits from remotely sensed data has become a major objective to extend the use
      of ocean colour data beyond chlorophyll a retrievals. Here, a new forward and
      inverse modelling structure is proposed to determine information about the cell
      size of phytoplankton communities using Standard size distributions of two
      layered spheres to derive a full suite of algal inherent optical properties for a
      coupled radiative transfer model. This new capability allows explicit
      quantification of the remote sensing reflectance signal attributable to changes
      in phytoplankton cell size. Inversion of this model reveals regions within the
      parameter space where ambiguity may limit potential of inversion algorithms.
      Validation of the algorithm within the Benguela upwelling system using
      independent data shows promise for ecosystem applications and further
      investigation of the interaction between phytoplankton functional types and
      optical signals. The results here suggest that the utility of assemblage related
      signals in spectral reflectance is highly sensitive to algal biomass, the
      presence of other absorbing and scattering constituents and the resultant
      constituent-specific inherent optical property budget. As such, optimal methods
      for determining phytoplankton size from (in situ or satellite) ocean colour data
      will likely rely on appropriately spectrally dense and optimised sensors, well
      characterised measurement errors including those from atmospheric correction, and
      an ability to appropriately limit ambiguity within the context of regional
      inherent optical properties. 

PMID- 24921276
TI  - Reconstruction of wave front and object for inline holography from a set of
      detection planes.
AB  - We illustrate the errors inherent in the conventional empty beam correction of
      full field X-ray propagation imaging, i.e. the division of intensities in the
      detection plane measured with an object in the beam by the intensity pattern
      measured without the object, i.e. the empty beam intensity pattern. The error of
      this conventional approximation is controlled by the ratio of the source size to
      the smallest feature in the object, as is shown by numerical simulation. In a
      second step, we investigate how to overcome the flawed empty beam division by
      simultaneous reconstruction of the probing wavefront (probe) and of the object,
      based on measurements in several detection planes (multi-projection approach).
      The algorithmic scheme is demonstrated numerically and experimentally, using the
      defocus wavefront of the hard X-ray nanoprobe setup at the European Synchrotron
      Radiation Facility (ESRF). 

PMID- 24921277
TI  - Extremely long decay time optical cavity.
AB  - We report on the resonant Fabry Perot cavity of the PVLAS (Polarization of the
      Vacuum with LASer) experiment operating at lambda = 1064 nm with a record decay
      time of 2.7 ms, a factor more than two larger than any previously reported
      optical resonator. This corresponds to a coherence length of 8.1 . 10(5) m. The
      cavity length is 3.303 m, and the resulting finesse is 770,000.

PMID- 24921278
TI  - Efficient diode-pumped Tm:KYW 1.9-MUm microchip laser with 1 W cw output power.
AB  - We report on a diode-pumped Tm:KYW microchip laser generating 1 W continuous-wave
      output power. The laser operates at a wavelength of 1.94 MUm in the fundamental
      TEM(00) mode with 71% slope efficiency relative to the absorbed pump radiation
      and 59% slope efficiency relative to the incident pump radiation. The optical-to
      optical laser efficiency is 43%.

PMID- 24921279
TI  - A high-finesse broadband optical cavity using calcium fluoride prism
      retroreflectors.
AB  - A high-finesse broadband optical cavity has been developed for use in the
      ultraviolet and visible region using Brewster-angle calcium fluoride (CaF2) prism
      retroreflectors. Prior to prism construction, optical loss measurements of CaF2
      windows were performed using cavity ring-down spectroscopy at 250 nm. Total
      optical loss showed high spatial correlation with crystal birefringence, which
      was partially mitigated by orienting the <111> crystal axis with the laser beam.
      Prism reflectivity was measured using cavity ring-down spectroscopy and found to
      be 99.77% at 250 nm and 99.96% at 500 nm, allowing for relatively high-finesse
      operation over hundreds of nm bandwidth with a single cavity.

PMID- 24921280
TI  - Passive intrinsic-linewidth narrowing of ultraviolet extended-cavity diode laser
      by weak optical feedback.
AB  - We present a simple method for narrowing the intrinsic Lorentzian linewidth of a
      commercial ultraviolet grating extended-cavity diode laser (TOPTICA DL Pro) using
      weak optical feedback from a long external cavity. We achieve a suppression in
      frequency noise spectral density of 20 dB measured at frequencies around 1 MHz,
      corresponding to the narrowing of the intrinsic Lorentzian linewidth from 200 kHz
      to 2 kHz. Provided additional active low-frequency noise suppression and long
      term drift compensation, the system is suitable for experiments requiring a
      tunable ultraviolet laser with narrow linewidth and low high-frequency noise,
      such as precision spectroscopy, optical clocks, and quantum information science
      experiments. 

PMID- 24921281
TI  - Theoretical and experimental analysis of pulse delay in bacteriorhodopsin films
      by a saturable absorber theory.
AB  - Time-delay of transmitted pulses with respect to the incident pulse in
      bacteriorhodopsin films has been studied without the use of a pump beam. Based on
      a modified saturable absorber model, analytical expressions of the transmitted
      pulse have been obtained. As a result, time delay, distortion and fractional
      delay have been analyzed for sinusoidal pulses with a low background. A good
      agreement between theory and experiences has been observed. 

PMID- 24921282
TI  - All-fiber fused directional coupler for highly efficient spatial mode conversion.
AB  - We model and demonstrate a simple mode selective all-fiber coupler capable of
      exciting specific higher order modes in two- and few-mode fibres with high
      efficiency and purity. The coupler is based on inter-modally phase-matching the
      propagation constants in each arm of the asymmetric fused coupler, formed by
      dissimilar fibres. At a specific coupler diameter, the launched fundamental
      LP(01) mode is coupled into the higher order mode (LP(11), LP(21), LP(02)) in the
      other arm, over a broadband wave-length range around 1550 nm. Unlike other
      techniques, the demonstrated coupler is composed of a multimode fiber that is
      weakly fused with a phase matched conventional single mode telecom fiber (SMF
      28). The beating between the supermodes at the coupler waist produces a periodic
      power transfer between the two arms, and therefore, by monitoring the beating
      while tapering, it is possible to obtain optimum selection for the desired mode.
      High coupling efficiencies in excess of 90% for all the higher order modes were
      recorded over 100 nm spectral range, while insertion losses remain as low as 0.5
      dB. Coupling efficiency can be further enhanced by performing slow tapering at
      high temperature, in order to precisely control the coupler cross-section
      geometry.

PMID- 24921283
TI  - Comparison of 80 * 112-Gb/s PDM-QPSK system performance over large effective area
      fiber and standard SMF with Raman amplification.
AB  - We experimentally investigate the transmission performance of 80 * 112-Gb/s
      polarization-division-multiplexed quadrature phase shift keying (PDM-QPSK)
      signals over large effective area fiber and standard single mode fiber (SSMF)
      links with Raman amplification. The large effective area fiber offers higher
      optimum launch power and longer reach than SSMF. The maximum reach of 5200-km is
      obtained using large effective area fiber. The Gaussian noise (GN) model is
      explored to fit with experimental data for optimum power. 

PMID- 24921284
TI  - Lateral photovoltaic effect and electron transport observed in Cr nano-film.
AB  - Lateral photovoltaic effect (LPE) can be used in position-sensitive detectors
      (PSDs) and has a wide application in a variety of optical transducers and
      sensors. In this report, a large LPE with sensitivity of 42mV/mm is observed in
      metal-oxide-semiconductor (MOS) structure of Cr/SiO(2)/Si. Through measuring
      current-voltage characteristics, we find that electron transport property in dark
      plays a key role and an appropriate metal thickness is crucial for obtaining a
      large LPE. This result is useful for applications and may explore a way to study
      the electron transport mechanism in nano-films' MOS structures.

PMID- 24921285
TI  - Symmetry-reduced double layer metallic grating structure for dual-wavelength
      spectral filtering.
AB  - In this paper, we propose a metal-dielectric dual-wavelength spectral filtering
      structure based on symmetry-reduced double layer metallic gratings (SRDMG)
      coupled to a guided-mode dielectric resonator. The grating symmetry is reduced by
      alternatively shifting metal nanowires of the top layer metallic grating.
      Compared to a symmetric double layer metallic grating that usually provides one
      resonance dip, this SRDMG structure generates two remarkable narrow band
      transmission dips with a transmission peak in-between at normal incidence. The
      appearance of the two narrowband resonance dips is attributed to the excitation
      of different current modes in the metallic grating, leading to different guided
      mode resonances in the dielectric layer, which is induced by the structural
      symmetry breaking. Moreover, these two guided modes do not split under oblique
      incidence and a flat dispersion band over a small angular range can be obtained.
      The positions of two dips and the frequency gap between them can be controlled by
      adjusting the thickness of metallic grating without the need to modify the
      structure period and width, which is an easy method to tune resonance position
      and bandwidth, and make the fabrication of some filters more convenient. This
      work can be used to develop subwavelength metallic-grating-based multi-wavelength
      and narrow-band spectral filters. 

PMID- 24921286
TI  - Lattice surface solitons in diffusive nonlinear media driven by the quadratic
      electro-optic effect.
AB  - We study theoretically surface lattice solitons driven by quadratic electro-optic
      effect at the interface between an optical lattice and diffusive nonlinear media
      with self-focusing and self-defocusing saturable nonlinearity. Surface solitons
      originating from self-focusing nonlinearity can be formed in the semi-infinite
      gap, and are stable in whole domain of their existence. In the case of self
      defocusing nonlinearity, both surface gap and twisted solitons are predicted in
      first gap. We discover that surface gap solitons can propagate stably in whole
      existence domain except for an extremely narrow region close to the Bloch band,
      and twisted solitons are linearly unstable in the entire existence domain. 

PMID- 24921287
TI  - Optical absorption and photocurrent enhancement in semi-insulating gallium
      arsenide by femtosecond laser pulse surface microstructuring.
AB  - We observe an enhancement of optical absorption and photocurrent from semi
      insulating gallium arsenide (SI-GaAs) irradiated by femtosecond laser pulses. The
      SI-GaAs wafer is treated by a regeneratively amplified Ti: Sapphire laser of 120
      fs laser pulse at 800 nm wavelength. The laser ablation induced 0.74 MUm periodic
      ripples, and its optical absorption-edge is shifted to a longer wavelength.
      Meanwhile, the steady photocurrent of irradiated SI-GaAs is found to enhance 50%.
      The electrical properties of samples are calibrated by van der Pauw method. It is
      found that femtosecond laser ablation causes a microscale anti-reflection coating
      surface which enhances the absorption and photoconductivity. 

PMID- 24921288
TI  - A versatile integrating sphere based photoacoustic sensor for trace gas
      monitoring.
AB  - A compact versatile photoacoustic (PA) sensor for trace gas detection is
      reported. The sensor is based on an integrating sphere as the PA absorption cell
      with an organ pipe tube attached to increase the sensitivity of the PA sensor.
      The versatility and enhancement of the sensitivity of the PA signal is
      investigated by monitoring specific ro-vibrational lines of CO(2) in the 2 MUm
      wavelength region and of NO(2) in the 405 nm region. The measured enhancement
      factor of the PA signal exceeds 1200, which is due to the acoustic resonance of
      the tube and the absorption enhancement of the integrating sphere relatively to a
      non-resonant single pass cell. It is observed that the background absorption
      signals are highly attenuated due to the thermal conduction and diffusion effects
      in the polytetrafluoroethylene cell walls. This demonstrates that careful choice
      of cell wall materials can be highly beneficial to the sensitivity of the PA
      sensor. These properties makes the sensor suitable for various practical sensor
      applications in the ultraviolet (UV) to the near infrared (NIR) wavelength
      region, including climate, environmental and industrial monitoring.

PMID- 24921289
TI  - Diffraction of cosine-Gaussian-correlated Schell-model beams.
AB  - The expression of spectral density of cosine-Gaussian-correlated Schell-model
      (CGSM) beams diffracted by an aperture is derived, and used to study the changes
      in the spectral density distribution of CGSM beams upon propagation, where the
      effect of aperture diffraction is emphasized. It is shown that, comparing with
      that of GSM beams, the spectral density distribution of CGSM beams diffracted by
      an aperture has dip and shows dark hollow intensity distribution when the order
      parameter n is big enough. The central intensity increases with increasing
      truncation parameter of aperture. The comparative study of spectral density
      distributions of CGSM beams with aperture and that of without aperture is
      performed. Furthermore, the effect of order-parameter n and spatial coherence of
      CGSM beams on the spectral density distribution is discussed in detail. The
      results obtained may be useful in optical particulate manipulation.

PMID- 24921290
TI  - Raman scattering reveals strong LO-phonon-hole-plasmon coupling in nominally
      undoped GaAsBi: optical determination of carrier concentration.
AB  - We report room-temperature Raman scattering studies of nominally undoped (100)
      GaAs1-xBix epitaxial layers exhibiting Bi-induced (p-type) longitudinal-optical
      plasmon-coupled (LOPC) modes for 0.018 <= x <= 0.048. Redshifts in the GaAs-like
      optical modes due to alloying are evaluated and are paralleled by strong damping
      of the LOPC. The relative integrated Raman intensities of LO(Gamma) and LOPC
      ALO/ALOPC are characteristic of heavily doped p-GaAs, with a remarkable near
      total screening of the LO(Gamma) phonon (ALO/ALOPC -> 0) for larger Bi
      concentrations. A method of spectral analysis is set out which yields estimates
      of hole concentrations in excess of 5*1017cm-3 and correlates with the Bi molar
      fraction. These findings are in general agreement with recent electrical
      transport measurements performed on the alloy, and while the absolute size of the
      hole concentrations differ, likely origins for the discrepancy are discussed. We
      conclude that the damped LO-phonon-hole-plasmon coupling phenomena plays a
      dominant role in Raman scattering from unpassivated nominally undoped GaAsBi.

PMID- 24921291
TI  - Mechanical Faraday effect for orbital angular momentum-carrying beams.
AB  - When linearly polarised light is transmitted through a spinning window, the plane
      of polarisation is rotated. This rotation arises through a phase change that is
      applied to the circularly polarised states corresponding to the spin angular
      momentum (SAM). Here we show an analogous effect for the orbital angular momentum
      (OAM), where a differential phase between the positive and negative modes (+/-l)
      is observed as a rotation of the transmitted image. For normal materials, this
      rotation is on the order of a micro radian, but by using a slow-light medium, we
      show a rotation of a few degrees. We also note that, within the bounds of our
      experimental parameters, this rotation angle does not exceed the scale of the
      spatial features in the beam profile.

PMID- 24921292
TI  - Optical transmission of planar metallic films coated by two-dimensional colloidal
      crystals.
AB  - Optical transmissions through a continuous planar metal film (without holes) with
      two-dimensional colloidal crystals coated on one or both interfaces have been
      experimentally and numerically investigated. Enhanced optical transmissions in
      the near-infrared regime can be observed for the metal film with identical two
      dimensional colloidal crystals coated on both sides, which occur due to the
      resonant tunneling of surface polariton Bloch eigenmodes excited on periodically
      structured interfaces. Numerical simulations of transmission spectra show an
      excellent agreement with the measured ones. Additionally, the numerical
      simulations reveal that the intensity of tunneling transmission is strongly
      dependent on the relative shift of the two-dimensional colloidal crystals on the
      opposite interfaces of the metallic film. 

PMID- 24921293
TI  - Enhanced asymmetric transmission due to Fabry-Perot-like cavity.
AB  - In this paper, a three layered metamaterial composed of a ring-chain structure
      sandwiched between two layers of twisted sub-wavelength cut-wire arrays is
      proposed and investigated. The designed structure is optimized such that
      asymmetric transmission with an extremely broad bandwidth, sharp rejection stop
      band and high transmittance is achieved. The physical mechanism is accounted for
      that the metallic layers form the Fabry-Perot-like resonance cavity, enhancing
      the polarization conversion efficiency between two orthogonal linearly polarized
      waves. To some extent, this approach offers a way to strengthen asymmetric
      transmission effect.

PMID- 24921294
TI  - Spontaneous emission inhibition of telecom-band quantum disks inside single
      nanowire on different substrates.
AB  - We investigate the inhibited spontaneous emission of telecom-band InAs quantum
      disks (Qdisks) in InP nanowires (NWs). We have evaluated how the inhibition is
      affected by different disk diameter and thickness. We also compared the
      inhibition in standing InP NWs and those NWs laying on silica (SiO(2)), and
      silicon (Si) substrates. We found that the inhibition is altered when we put the
      NW on the high-refractive-index materials of Si. Experimentally, the inhibition
      factor zeta of the Qdisk emission at 1,500 nm decreases from 4.6 to 2.5 for NW on
      SiO(2) and Si substrates, respectively. Those inhibitions are even much smaller
      than that of 6.4 of the standing NW. The inhibition factors well agree with those
      calculated from the coupling of the Qdisk to the fundamental guided mode and the
      continuum of radiative modes. Our observation can be useful for the integration
      of the NW as light sources in the photonic nanodevices.

PMID- 24921295
TI  - Fast physical random bit generation with photonic integrated circuits with
      different external cavity lengths for chaos generation.
AB  - We generate random bit sequences from chaotic temporal waveforms by using
      photonic integrated circuits (PICs) with different external cavity lengths. We
      investigate the condition for generating random bits at different sampling rates
      of single-bit generation method with the PICs. We succeed in generating certified
      random bit sequences by using the PIC with 3, 4, 5, or 10-mm-long external
      cavity, whereas random bits cannot pass all the statistical tests of randomness
      when the PIC with 1 or 2 mm-long external cavity is used.

PMID- 24921296
TI  - A semi-analytical model for the approximation of plasmonic bands in arrays of
      metal wires in photonic crystal fibers.
AB  - We present a highly efficient semi-analytical and straightforward-to-implement
      model for the determination of plasmonic band edges of metallic nanowire arrays
      inside photonic crystal fibers. The model relies on the approximation of the
      hexagonal unit cell by a circle and using particular boundary conditions, showing
      an accurate agreement with finite element simulations. The model reduces
      simulation time by a factor of 100, thus representing an efficient tool for
      structure design. It further allows the calculation of all relevant modes in the
      system by slight changes of the entries in a 4 * 4 matrix. 

PMID- 24921297
TI  - Photothermal optical coherence tomography based on the localized surface plasmon
      resonance of Au nanoring.
AB  - The conventional optical coherence tomography (OCT) images based on enhanced
      scattering and the photothermal (PT) images based on enhanced absorption of the
      localized surface plasmon (LSP) resonance of Au nanorings (NRIs) in a bio-tissue
      sample are demonstrated with the scans of an OCT system (1310-nm system), in
      which the spectral range covers the LSP resonance peak wavelength, and another
      OCT system (1060-nm system), in which the spectral range is away from the LSP
      resonance peak wavelength. A PT image is formed by evaluating the modulation
      frequency (400 Hz) response of an excitation laser with its wavelength (1308 nm)
      close to the LSP resonance peak at 1305 nm of the Au NRI solution. With the scan
      of the 1310-nm OCT system, the Au NRI distribution in the bio-tissue sample can
      be observed in both conventional OCT and PT images. However, with the scan of the
      1060-nm OCT system, the Au NRI distribution can be clearly observed only in the
      PT image. The diffusion process of Au NRIs in the bio-tissue sample can be traced
      with the scan of either OCT system. Based on phantom experiments, it is shown
      that the PT image can help in resolving the ambiguity of a conventional OCT image
      between the enhanced scattering of Au NRIs and the strong scattering of a tissue
      structure in the 1310-nm OCT scanning. Also, under the condition of weak
      intrinsic sample scattering, particularly in the scan of the 1060-nm system, the
      PT signal can be lower than a saturating level, which is determined by the
      excitation power. By increasing OCT system signal-to-noise ratio or M-mode scan
      time, the PT signal level can be enhanced. 

PMID- 24921298
TI  - Suppression of Rayleigh backscattering noise using cascaded-SOA and microwave
      photonic filter for 10 Gb/s loop-back WDM-PON.
AB  - In this paper, we present a novel Rayleigh backscattering (RB) noise mitigation
      scheme based on central carrier suppression for 10 Gb/s loop-back wavelength
      division multiplexing passive optical network (WDM-PON). Microwave modulated
      multi-subcarrier optical signal is used as downstream seeding light, while
      cascaded semiconductor optical amplifier (SOA) are used in the optical network
      unit (ONU) for suppressing the central carrier of the multi-subcarrier upstream
      signal. With central carrier suppression, interference generated by carrier RB
      noise at low frequency region is eliminated successfully. Transmission
      performance over 45 km single mode fiber (SMF) is studied experimentally, and the
      optical-signal-to-Rayleigh-noise-ratio (OSRNR) can be reduced to 15 dB with
      central carrier suppression ratio (CCSR) of 21 dB. Receiver sensitivity is
      further improved by 6 dB with the use of microwave photonic filter (MPF) for
      suppressing residual upstream microwave signal and residual carrier RB at high
      frequency region.

PMID- 24921299
TI  - Highly efficient active optical interconnect incorporating a partially
      chlorinated ribbon POF in conjunction with a visible VCSEL.
AB  - A low-loss 4-ch active optical interconnect (AOI) enabling passive alignment was
      proposed and built resorting to a transmitter (Tx) incorporating a red 680-nm
      VCSEL, which is linked to a receiver (Rx) module via a partially chlorinated
      ribbon POF. The POF was observed to exhibit an extremely low loss of ~0.24 dB/m
      at lambda = 680 nm, in comparison to ~1.29 dB/m at lambda = 850 nm, and a large
      numerical aperture of ~0.42. Both the Tx and Rx, which taps into a beam router
      based on collimated beam optics involving a pair of spherical lenses, were meant
      to be substantially alignment tolerant and compact. The achieved tolerance for
      the constructed modules was beyond 40 MUm in terms of the positioning of VCSEL
      and photodetector. The proposed AOI was completed by linking the Tx with the Rx
      via a 3-m long ribbon POF, incurring a transmission loss of as small as 3.2 dB.
      The AOI was practically assessed in terms of a high-speed data transmission over
      a wide range of temperatures and then exploited to convey full HD video signals.

PMID- 24921300
TI  - Time-domain stabilization of carrier-envelope phase in femtosecond light pulses.
AB  - We report a time-domain method of stabilizing the carrier-envelope phase (CEP) of
      femtosecond pulses. Temporal variations of the pulse envelope and the carrier
      electric-field phase were separately detected with the aid of intensity cross
      correlation and interferometric cross-correlation. These detected signals were
      used to stabilize the CEP; the resulting 50-fold improvement in the fractional
      stability of the carrier-envelop-offset frequency was evaluated as 1.2 * 10(-11)
      at 0.1 second averaging periods and 1.7 * 10(-9) at 80 seconds, corresponding to
      a carrier envelope phase noise of 75 microradians and 10 milliradians,
      respectively. This method can be realized with a low pulse energy of ~10 pJ and
      does not require subsequent power amplification or spectral broadening. The high
      efficiency and short-term stability of this method can facilitate the use of
      femtosecond lasers in the field of industrial surface measurements,
      telecommunications, and space sciences.

PMID- 24921301
TI  - Role of resonance absorption in terahertz radiation generation from solid
      targets.
AB  - The interaction of 100-fs laser pulses with solid targets at laser intensities
      10(16)-10(18)W/cm(2) has been investigated experimentally by simultaneous
      measurements of terahertz (THz) and second harmonic signals. THz yield at the
      front side of the target, which rises from the self-organized transient electron
      currents along the target surface, is found scaling linearly with the laser
      intensity basically. Measurements of specularly reflected light spectrum show
      clear evidence of resonance absorption. The positive effects of resonance
      absorption on surface current and THz radiation generation have been confirmed by
      two-dimensional (2D) particle-in-cell (PIC) simulations and angular-dependent
      experiments, respectively.

PMID- 24921302
TI  - Two dimensional analysis of finite size high-contrast gratings for applications
      in VCSELs.
AB  - 2-dimensional simulations of high-contrast gratings (HCGs) of finite size are
      carried out, targeting at their applications in vertical-cavity surface-emitting
      lasers (VCSELs). Finite HCGs show a very different behavior from infinite grating
      ones. The reflectivity of a finite HCG strongly depends on the HCG size and the
      source size. Our simulation results predict finite reflectivity and transmission
      values, well consistent with reported experimental results. The band of high
      reflectivity (>99.5%) of finite HCGs is less broad as compared to the infinite
      case. Losses into a guided mode excited in the HCG plane are identified as being
      at the root. This guided mode is excited due to the nonzero angular components in
      the finite source size, and greatly enhances the transmission and the light
      leakage from the slab. In addition, the simulation results show that the details
      of the finite HCG can shape the output beam, whilst a Gaussian-like reflected
      wave is typically achieved. Our simulations can explain the current discrepancies
      between numerical predictions of reflectivities approaching 100% and working HCG
      VCSELs showing finite reflectivities and nearly Gaussian-like output.
      Consequently, our analysis of finite HCGs is indispensable for HCG-VCSEL design.

PMID- 24921303
TI  - Linear rotary optical delay lines.
AB  - I present several classes of analytical and semi-analytical solutions for the
      design of high-speed rotary optical delay lines that use a combination of
      stationary and rotating curvilinear reflectors. Detailed analysis of four
      distinct classes of optical delay lines is presented. Particularly, I consider
      delay lines based on a single rotating reflector, a single rotating reflector and
      a single stationary reflector, two rotating reflectors, and two rotating
      reflectors and a single stationary reflector. I demonstrate that in each of these
      cases it is possible to design an infinite variety of the optical delay lines
      featuring linear dependence of the optical delay on the rotation angle. This is
      achieved via shape optimization of the rotating and stationary reflector
      surfaces. Moreover, in the case of two rotating reflectors a convenient spatial
      separation of the incoming and outgoing beams is possible. For the sake of
      example, all the blades presented in this paper are chosen to fit into a circle
      of 10 cm diameter and these delay lines feature in excess of 600 ps of optical
      delay. Finally, two prototypes of rotary delay lines were fabricated using CNC
      machining, and their optical properties are characterized.

PMID- 24921304
TI  - Reflective liquid level sensor based on modes conversion in thin-core fiber
      incorporating titled fiber Bragg grating.
AB  - A simple and compact reflective liquid level sensor based on modes conversion in
      the thin-core fiber incorporating one tilted fiber Bragg grating (TFBG) is
      proposed and experimentally demonstrated. A piece of thin-core fiber containing
      one TFBG ensures the modes conversion between the core mode and cladding modes.
      The external liquid can induce the cladding modes covert to the radiation modes
      and lead to the decrement of the collected cladding modes power, then the liquid
      level can be measured from the collected cladding modes power. The modes
      conversion in the proposed structure is theoretically analyzed. The experimental
      results show the high liquid level sensitivity and temperature immunity of the
      proposed sensor, and its significant advantage is that the measurement range is
      not limited to the length of the TFBG itself. 

PMID- 24921305
TI  - 1.14 Tb/s DP-QPSK WDM polarization-diverse optical phase conjugation.
AB  - Optical phase conjugation (OPC) of a polarization-multiplexed comb of 10x114Gb/s
      DP-QPSK signals has been demonstrated for the first time, occupying a spectral
      bandwidth of >1 THz (~9 nm). The nonlinear element employed for the OPC was
      highly nonlinear fiber (HNLF) optimized for the suppression of stimulated
      Brillouin scattering (SBS) and configured in a bi-directional loop offering
      polarization diversity. Pump power (each way about the loop) and input signal
      power to the OPC subsystem were optimized at 29.7 dBm and + 3 dBm respectively
      producing a Q(2) penalty of <= 0.9 dB over all conjugate wavelengths,
      polarizations and output OSNR (up to 20 dB).

PMID- 24921306
TI  - Spectrally-resolved statistical characterization of seeded supercontinuum
      suppression using optical time-stretch.
AB  - Real-time experimental measurements of the spectrally-resolved noise properties
      of supercontinuum (SC) have been challenging because of the lack of ultrafast
      optical spectrometer technologies. Understanding the SC noise is increasingly
      important because it not only can gain new insight of the complex spectral
      dynamics of SC generation, but also provides clues to search for stable SC
      source. Driven by the intense interest in the active seeding mechanism for SC
      generation, we experimentally demonstrate real-time spectrally-resolved,
      broadband, statistical characterization of minute continuous-wave (CW) seeded SC,
      enabled by an ultrahigh-speed spectral acquisition technique called optical time
      stretch (OTS). The shot-to-shot statistical analysis shows that the seeded SC
      exhibits a general compromise between SC bandwidth and spectral stability. OTS
      also allows us to experimentally identify the seeding condition for SC
      suppression, in which the spectral broadening is mainly contributed by the
      cascaded parametric process that delays Akhmediev Breather breakup process and
      subsequent soliton self-frequency shift. Additionally, the characteristic
      spectral signature of the Raman solitons, which are becalmed by the minute CW
      seed, can be clearly captured in real-time by OTS operated at a spectral
      acquisition rate as high as 20 MHz. We anticipate the OTS technique could provide
      further new insights for understanding more complex mechanisms of seeded-SC
      generation which can be examined experimentally. 

PMID- 24921307
TI  - Break up of the azimuthal symmetry of higher order fiber modes.
AB  - We investigate Bessel-like modes guided in a double cladding fiber where the
      outer cladding is an aircladding. For very high order LP(0X) -modes, the
      azimuthal symmetry is broken and the mode is no longer linearly polarized. This
      is observed experimentally and confirmed numerically. The effect is investigated
      numerically using a full vectorial modesolver and is observed to be dependent on
      the fiber design. The effect on the diffraction free propagation distance of the
      modes is investigated using a fast Fourier transform propagation routine and
      compared to the properties of an ideal circularly symmetric mode. The free space
      properties of modes suffering from break up of azimuthal symmetry are also
      investigated experimentally by measuring the free space propagation of a LP(016)
      mode excited in the double cladding fiber.

PMID- 24921308
TI  - Measurement errors resulted from misalignment errors of the retarder in a
      rotating-retarder complete Stokes polarimeter.
AB  - Rotatable retarder fixed polarizer (RRFP) Stokes polarimeters, which employ
      uniformly spaced angles over 180 degrees  or 360 degrees , are most commonly used
      to detect the state of polarization (SOP) of an electromagnetic (EM) wave. The
      misalignment error of the retarder is one of the major error sources. We suppose
      that the misalignment errors of the retarder obey a uniform normal distribution
      and are independent of each other. Then, we derive analytically the covariance
      matrices of the measurement errors. Based on the covariance matrices derived, we
      can conclude that 1) the measurement errors are independent of the incident
      intensity s0, but seriously depend on the Stokes parameters (s1, s2, s3) and the
      retardance of the retarder delta; 2) for any mean incident SOP, the optimal
      initial angle and retardance to minimize the measurement error both can be
      achieved; 3) when N = 5, 10, 12, the initial orienting angle could be used as an
      added degree of freedom to strengthen the immunity of RRFP Stokes polarimeters to
      the misalignment error. Finally, a series of simulations are performed to verify
      these theoretical results.

PMID- 24921309
TI  - High peak power gigahertz Yb:CALGO laser.
AB  - We present a high-power gigahertz SESAM modelocked Yb:CALGO laser with sub-60-fs
      pulses. The laser delivers an average output power of 2.95 W at a pulse
      repetition rate of 1.8 GHz in fundamental modelocking without additional pulse
      compression or amplification. Stable modelocking with a single pulse per cavity
      round-trip is confirmed and results in an output peak power of 24.3 kW and a
      pulse energy of 1.64 nJ. The laser is pumped by a commercial multimode diode
      laser, which improves the reliability and robustness. This high-power gigahertz
      laser is expected to enable numerous applications in frequency metrology.

PMID- 24921310
TI  - Dielectric multilayer-based fiber optic sensor enabling simultaneous measurement
      of humidity and temperature.
AB  - A multilayer-based fiber optic sensor enabling simultaneous measurement of
      humidity and temperature is proposed and demonstrated. The sensitive elements
      were multilayer coatings consisting of nano-porous TiO(2) and SiO(2) films, which
      were deposited on fiber end-face to form a Fabry-Perot (F-P) filter structure.
      Relative-humidity (RH) sensing is correlated with the shift of interference
      fringe due to the change of effective refractive index of porous coatings when
      exposed to different RH environments. The sensor is sealed in a glass tube in
      case of temperature measurement. Experimental results show that the average
      sensitivity are 0.43nm/%RH and 0.63nm/ degrees C respectively when environmental
      RH changes from 1.8%RH to 74.7%RH and temperature changes from 21.4 degrees C to
      38.8 degrees C. The proposed sensors present high repeatability, and especially
      highly sensitive to lower moisture measure.

PMID- 24921311
TI  - Vector nature of multi-soliton patterns in a passively mode-locked figure-eight
      fiber laser.
AB  - The vector nature of multi-soliton dynamic patterns was investigated in a
      passively mode-locked figure-eight fiber laser based on the nonlinear amplifying
      loop mirror (NALM). By properly adjusting the cavity parameters such as the pump
      power level and intra-cavity polarization controllers (PCs), in addition to the
      fundamental vector soliton, various vector multi-soliton regimes were observed,
      such as the random static distribution of vector multiple solitons, vector
      soliton cluster, vector soliton flow, and the state of vector multiple solitons
      occupying the whole cavity. Both the polarization-locked vector solitons (PLVSs)
      and the polarization-rotating vector solitons (PRVSs) were observed for
      fundamental soliton and each type of multi-soliton patterns. The obtained results
      further reveal the fundamental physics of multi-soliton patterns and demonstrate
      that the figure-eight fiber lasers are indeed a good platform for investigating
      the vector nature of different soliton types.

PMID- 24921312
TI  - Lasing of TM modes in a two-dimensional GaAs microlaser.
AB  - We fabricated and tested an unstrained GaAs single-quantum-well microlaser which
      has a two-dimensional cavity shape known as the Penrose unilluminable room. The
      cavity exhibits quasi-one-dimensional modes, namely axial, diamond-shaped, and V
      shaped modes. In contrast to previous observations of TE-polarized emission in
      GaAs microlasers, we observed TM-polarized emission. We explain this observation
      as being the result of lasing of the diamond-shaped modes whose incident angle at
      the cavity interface is very close to the Brewster angle.

PMID- 24921313
TI  - Digital phase conjugate mirror by parallel arrangement of two phase-only spatial
      light modulators.
AB  - In a conventional digital phase conjugation system, only the phase of an input
      light is time-reversed. This deteriorates phase conjugation fidelity and
      restricts application fields to specific cases only when the input light has
      uniformly-distributed scattered wavefront. To overcome these difficulties, we
      present a digital phase conjugate mirror based on parallel alignment of two phase
      only spatial light modulators (SLMs), in which both amplitude and phase of the
      input light can be time-reversed. Experimental result showed that, in the phase
      conjugation through a holographic diffuser with diffusion angle of 0.5 degree,
      background noises decrease to 65% by our digital phase conjugation mirror.

PMID- 24921314
TI  - X-ray diffraction tomography employing an annular beam.
AB  - We demonstrate depth-resolved materials characterization by scanning a sample
      through an annular beam of X-rays. We measure Bragg X-ray diffraction from a
      sample with a planar detector positioned centrally in a circular dark field
      defined by the annular beam. The diffraction maxima are optically encoded with
      the position of crystalline phases along this beam. Depth-resolved material phase
      images are recovered via tomosynthesis. We demonstrate our technique using a
      heterogeneous three-dimensional object comprising three different phases;
      cyclotetramethylene - tetranitramine, copper and nickel, distributed in a low
      density medium. Our technique has wide applicability in analytical imaging and is
      scalable with respect to both scan size and X-ray energy.

PMID- 24921315
TI  - Super-resolved phase measurements at the shot noise limit by parity measurement.
AB  - Classically, the resolution of optical measurements is limited by the Rayleigh
      limit and their sensitivity by the shot noise limit. However, non-classical
      measurements can surpass these limits. Measuring the photon number parity using a
      photon-number resolving detector, super resolved phase measurements up to 144
      better than the Rayleigh limit are presented, with coherent states of up to 4,200
      photons on average. An additional measurement that can be implemented with
      standard single-photon detectors is proposed and demonstrated. With this scheme,
      super resolution at the shot noise limit is demonstrated with coherent states of
      up to 200 photons on average. 

PMID- 24921316
TI  - Self-seeding-based 10Gb/s over 25km optical OFDM transmissions utilizing face-to
      face dual-RSOAs at gain saturation.
AB  - Self-seeded passive optical networks (PONs) are currently attracting extensive
      research interest. In this paper, a novel self-seeded PON transmitter is, for the
      first time, proposed and experimentally demonstrated, which incorporates two face
      to-face-positioned reflective semiconductor optical amplifiers (RSOAs) operating
      at their gain saturation regions: one RSOA directly driven by an upstream
      electrical signal and the other RSOA biased at a fixed current. Detailed
      experimental explorations are undertaken of the dynamic performance
      characteristics of the proposed transmitter. It is shown that, in comparison with
      previously reported self-seeded transmitters each employing a reflective mirror
      and a single electrical signal-driven RSOA, the proposed transmitter has a number
      of salient advantages including, considerably narrowed optical signal spectra, up
      to 16dB reduction in RINs of intensity-modulated optical signals, and residual
      intensity modulation crosstalk suppression as high as 10.7dB. The aforementioned
      features enable experimental demonstrations of real-time self-seeded 10Gb/s
      optical OFDM (OOFDM) transmitters. In particular, by making use of two low-cost
      RSOAs having their 3-dB modulation bandwidths as small as 1.125GHz, 10Gb/s over
      25km adaptive OOFDM transmissions with power penalties of 0.6dB are
      experimentally achieved in the simple self-seeded IMDD PON systems.

PMID- 24921317
TI  - Dielectric function of spherical dome shells with quantum size effects.
AB  - Metallic spherical dome shells have received much attention in recent years
      because they have proven to possess highly impressive optical properties. The
      expected distinctive changes occurring owing to quantum confinement of conduction
      electrons in these nanoparticles as their thickness is reduced, have not been
      properly investigated. Here we carry out a detailed analytical derivation of the
      quantum contributions by introducing linearly shifted Associated Legendre
      Polynomials, which form an approximate orthonormal eigenbasis for the single
      electron Hamiltonian of a spherical dome shell. Our analytical results clearly
      show the contribution of different elements of a spherical dome shell to the
      effective dielectric function. More specifically, our results provide an
      accurate, quantitative correction for the dielectric function of metallic
      spherical dome shells with thickness below 10 nm. 

PMID- 24921318
TI  - Polarimetric current sensor based on polarization division multiplexing
      detection.
AB  - A polarimetric current sensor based on polarization division multiplexing (PDM)
      detection is proposed. The novel sensor head with a heat insulation cavity only
      induces a small level of birefringence. Comparing with polarization diversity
      (PD) detection, the sensitivity of PDM detection is the double of PD detection.
      Moreover, PDM detection is more suitable in the presence of the phase modulation
      error. In addition, the noise and the shifting of the Verdet constant are proved
      to be the main influence factors of the sensor performance as the source power
      decline.

PMID- 24921319
TI  - Tellurite microspheres for nanoparticle sensing and novel light sources.
AB  - High index Er-Yb codoped tellurite spheres with diameter of 9 MUm and good
      sphericity were fabricated using a CO(2) laser. Upconversion modulated whispering
      gallery modes with a quality factor of 45,000 were observed in the sphere dipped
      in methanol. Refractometric sensing with detection sensitivity of 7.7 nm/RIU was
      demonstrated using a 9 MUm diameter sphere. Such high index spheres have the
      potential to be used for nanoparticle sensing and mid-IR frequency conversion.

PMID- 24921320
TI  - Dynamic range extension of SiPM detectors with the time-gated operation.
AB  - The silicon photomultiplier (SiPM) is a novel detector technology that has
      undergone a fast development in the last few years, owing to its single-photon
      resolution and ultra-fast response time. However, the typical high dark count
      rates of the sensor may prevent the detection of low intensity radiation fluxes.
      In this article, the time-gated operation with short active periods in the
      nanosecond range is proposed as a solution to reduce the number of cells fired
      due to noise and thus increase the dynamic range. The technique is aimed at
      application fields that function under a trigger command, such as gated
      fluorescence lifetime imaging microscopy. 

PMID- 24921321
TI  - Third-order nonlinear optical response and optical limiting of colloidal carbon
      dots.
AB  - In this work, the nonlinear optical response of some organophilic and hydrophilic
      carbon dots derived from gallate precursors is studied under 4 ns and 35 ps,
      visible (532 nm) and infrared (1064 nm) laser excitation conditions by the Z-scan
      technique. The prepared carbon dots were found to exhibit considerable nonlinear
      optical response in the visible, the organophilic ones exhibiting stronger
      response in the infrared and, in general, significantly larger response than
      their hydrophilic counterparts. In all cases, the corresponding nonlinear optical
      parameters have been determined. In particular, it was found that both carbon
      dots exhibited important negative nonlinear refractivity, under all excitation
      conditions tried, corresponding to self-defocusing, while negligible nonlinear
      absorption was found in the ps regime. Oppositely, both types of carbon dots were
      found to exhibit sizeable nonlinear absorption under ns excitation, indicating
      their potential for optical limiting applications. The present results are
      discussed and compared with other results concerning similar carbon based
      nanostructures reported in the literature. 

PMID- 24921322
TI  - Role of misalignment-induced angular chirp in the electro-optic detection of THz
      waves.
AB  - A general description of electro-optic detection including non-collinear phase
      matching and finite transverse beam profiles is presented. It is shown
      theoretically and experimentally that non-collinear phase matching in ZnTe (and
      similar materials) produces an angular chirp in the chi(2)-generated optical
      signal. Due to this, in non-collinear THz and probe arrangements such as single
      shot THz measurements or through accidental misalignment, measurement of an
      undistorted THz signal is critically dependent on having sufficient angular
      acceptance in the optical probe path. The associated spatial walk-off can also
      preclude the phase retardation approximation used in THz-TDS. The rate of
      misalignment-induced chirping in commonly used ZnTe and GaP schemes is tabulated,
      allowing ready analysis of a detection system.

PMID- 24921323
TI  - Spectral broadening and compression of sub-millijoule laser pulses in hollow-core
      fibers filled with sulfur hexafluoride.
AB  - Spectral broadening in gas-filled hollow-core fibers is discussed for sulfur
      hexafluoride, a molecular gas with Raman activity. Experimental results for
      compressed pulses are presented for input pulses longer than the Raman period and
      shorter than the dephasing time at a central wavelength of 800 nm and 400 nm,
      respectively. For both wavelengths we compress the pulses by a factor of three
      and maintain a good pulse quality. The obtained results are of interest for
      compressing pulses generated with Yb doped lasers. 

PMID- 24921324
TI  - Achromatic correction of diffractive dispersion in white light SLM imaging.
AB  - In contemporary optics, the spatial light modulator (SLM) is effectively used as
      a flexible optoelectronic device playing the key role in a number of experiments
      of science and technology. Its operation is optimal when using almost
      monochromatic light but an extremely strong diffractive dispersion occurs when
      white light is applied. In this paper, the design concepts are proposed resulting
      in optimization and implementation of a refractive corrector cooperating with the
      SLM. The corrector maintains the operation of the SLM unchanged for the central
      wavelength of light and ensures an achromatic dispersion compensation throughout
      the visible region in applications based on a lens-pattern formation. A
      significant improvement of the imaging performance of the achromatic SLM was
      proved by the computer simulation and measurement of the chromatic focal shift
      and the image contrast of the resolution target.

PMID- 24921325
TI  - First demonstration of a scalable MDM/CDM optical access system.
AB  - A novel hybrid all-optical mode-division multiplexing and code division
      multiplexing architecture for flexible and scalable access networks is presented.
      We successfully demonstrate, for the first time, an asynchronous on-off keying
      modulation, 2 mode x 4 code x 10 Gbps transmission over 42-km link, using a set
      of single-mode and two-mode fibers, without dispersion compensation. The four
      phase-shift keyed optical codes are generated at a single wavelength, by a
      multiport encoder/decoder, and we use an optical mode multiplexer/demultiplexer
      in the remote node and at the central office. We also experimentally evaluate the
      mode crosstalk tolerance considering different access span distances for the
      LP(01) and LP(11) modes.

PMID- 24921326
TI  - Brillouin optical correlation domain analysis with 4 millimeter resolution based
      on amplified spontaneous emission.
AB  - A new technique for Brillouin scattering-based, distributed fiber-optic
      measurements of temperature and strain is proposed, analyzed, simulated, and
      demonstrated. Broadband Brillouin pump and signal waves are drawn from the
      filtered amplified spontaneous emission of an erbium-doped fiber amplifier,
      providing high spatial resolution. The reconstruction of the position-dependent
      Brillouin gain spectra along 5 cm of a silica single-mode fiber under test, with
      a spatial resolution of 4 mm, is experimentally demonstrated using a 25 GHz-wide
      amplified spontaneous emission source. A 4 mm-long localized hot spot is
      identified by the measurements. The uncertainty in the reconstruction of the
      local Brillouin frequency shift is +/- 1.5 MHz. The single correlation peak
      between the pump and signal is scanned along a fiber under test using a
      mechanical variable delay line. The analysis of the expected spatial resolution
      and the measurement signal-to-noise ratio is provided. The measurement principle
      is supported by numerical simulations of the stimulated acoustic field as a
      function of position and time. Unlike most other Brillouin optical correlation
      domain analysis configurations, the proposed scheme is not restricted by the
      bandwidth of available electro-optic modulators, microwave synthesizers, or
      pattern generators. Resolution is scalable to less than one millimeter in highly
      nonlinear media. 

PMID- 24921327
TI  - Transmission of 100-Gb/s DDO-OFDM/OQAM over 320-km SSMF with a single photodiode.
AB  - In this paper, we propose a novel approach to simultaneously receive multi-band
      100-Gb/s direct-detection optical signal with only one polarization and one
      conventional 40-GHz photodiode. The modulation format of orthogonal frequency
      division multiplexing based on offset quadrature amplitude modulation (OFDM/OQAM)
      is selected to provide signal spectrum with high side-lobe suppression ratio,
      which can effectively reduce the electrical sub-band frequency interference. The
      whole 100-Gb/s OFDM/OQAM signal is comprised of 6 sub-bands with 16- and 32-QAM
      formats loading. Only one guard band is required to accommodate the overlapped 6
      band signal-to-signal beat interference (SSBI). The receiver bandwidth is mainly
      limited by the digital storage oscilloscope (DSO) of 33 GHz. The transmission
      distance over standard single mode fiber (SSMF) is up to 320 km.

PMID- 24921328
TI  - Finite-difference time-domain simulation of spacetime cloak.
AB  - In this work, we present a numerical method that remedies the instabilities of
      the conventional FDTD approach for solving Maxwell's equations in a space-time
      dependent magneto-electric medium with direct application to the simulation of
      the recently proposed spacetime cloak. We utilize a dual grid FDTD method
      overlapped in the time domain to provide a stable approach for the simulation of
      a magneto-electric medium with time and space varying permittivity, permeability
      and coupling coefficient. The developed method can be applied to explore other
      new physical possibilities offered by spacetime cloaking, metamaterials, and
      transformation optics.

PMID- 24921329
TI  - Gigahertz pulse source by compression of mode-locked VECSEL pulses coherently
      broadened in the normal dispersion regime.
AB  - We report the coherent spectral broadening of the output of a mode-locked VECSEL
      emitting 455 fs pulses at 1007 nm in the normal-dispersion regime. Subsequent
      compression of the fiber outputs using a transmission grating compressor produced
      1.56 GHz trains of 150 fs pulses at 270 mW average power or 220 fs pulses at 520
      mW average power. The system approaches the performance needed for a pump for
      coherent supercontinuum generation. 

PMID- 24921330
TI  - Recovery of Raman spectra with low signal-to-noise ratio using Wiener estimation.
AB  - Raman spectroscopy is a powerful non-destructive technique for qualitatively and
      quantitatively characterizing materials. However, noise often obscures
      interesting Raman peaks due to the inherently weak Raman signal, especially in
      biological samples. In this study, we develop a method based on spectral
      reconstruction to recover Raman spectra with low signal-to-noise ratio (SNR). The
      synthesis of narrow-band measurements from low-SNR Raman spectra eliminates the
      effect of noise by integrating the Raman signal along the wavenumber dimension,
      which is followed by spectral reconstruction based on Wiener estimation to
      recover the Raman spectrum with high spectral resolution. Non-negative principal
      components based filters are used in the synthesis to ensure that most variance
      contained in the original Raman measurements are retained. A total of 25 agar
      phantoms and 20 bacteria samples were measured and data were used to validate our
      method. Four commonly used de-noising methods in Raman spectroscopy, i.e.
      Savitzky-Golay (SG) algorithm, finite impulse response (FIR) filtration, wavelet
      transform and factor analysis, were also evaluated on the same set of data in
      addition to the proposed method for comparison. The proposed method showed the
      superior accuracy in the recovery of Raman spectra from measurements with
      extremely low SNR, compared with the four commonly used de-noising methods. 

PMID- 24921331
TI  - A printed nanobeam laser on a SiO2/Si substrate for low-threshold continuous-wave
      operation.
AB  - A small-footprint nanobeam photonic crystal laser made of InGaAsP material is
      directly integrated on a SiO2/Si substrate without using adhesive material via
      transfer-printing processes (i.e., dry transfer-printing). The transferred
      nanobeam structure with a physical volume of ~6.6 * 0.58 * 0.28 um(3) (~10.5
      (lambda/n)3) shows single mode lasing near 1550 nm with continuous-wave (CW)
      operation at room-temperature, where effective lasing threshold power was as low
      as 9 uW. This CW operation was achieved mainly due to efficient heat dissipation
      provided by direct contact between the nanobeam and the substrate. This transfer
      printed nanobeam laser could be a promising candidate for the next-generation
      light source with a feature of low-power consumption in ultracompact photonic
      integrated circuits.

PMID- 24921332
TI  - Hydrogenated amorphous silicon photonic device trimming by UV-irradiation.
AB  - A method to compensate for fabrication tolerances and to fine-tune individual
      photonic circuit components is inevitable for wafer-scale photonic systems even
      with most-advanced CMOS-fabrication tools. We report a cost-effective and highly
      accurate method for the permanent trimming of hydrogenated amorphous silicon
      photonic devices by UV-irradiation. Microring resonators and Mach-Zehnder
      interferometers were utilized as photonic test devices. The MZIs were tuned forth
      and back over their complete free spectral range of 5.5 nm by locally trimming
      the two MZI-arms. The trimming range exceeds 8 nm for compact ring resonators
      with trimming accuracies of 20 pm. Trimming speeds of >= 10 GHz/s were achieved.
      The components did not show any substantial device degradation. 

PMID- 24921333
TI  - Bistable light-driven pi phase switching using a twisted nematic liquid crystal
      film.
AB  - A light-activated optical phase switch was developed, exploiting the conversion
      between left-handed and right-handed twisted nematic liquid crystals. Theoretical
      and experimental analyses revealed that the handedness inversion of the twisted
      nematic film altered the optical phase of the output waves by pi. Herein, the
      competition between the helical twisting powers of the two reverse-handed chiral
      dopants determines the handedness of the twisted nematic film. The photo
      responsibility and the bistability are attributed to the azobenzene chromophores
      in one of the chiral additives. 

PMID- 24921334
TI  - Directly modulated buried heterostructure DFB laser on SiO2/Si substrate
      fabricated by regrowth of InP using bonded active layer.
AB  - We describe the growth of InP layer using an ultrathin III-V active layer that is
      directly bonded to SiO2/Si substrate to fabricate a buried heterostructure (BH)
      laser. Using a 250-nm-thick bonded active layer, we succeeded in fabricating a BH
      distributed feedback (DFB) laser on SiO2/Si substrate. The use of a lateral
      current injection structure is important for forming a p-i-n junction using
      bonded thin film. The fabricated DFB laser is directly modulated by a 25.8-Gbit/s
      NRZ signal at 50 degrees C. These results indicate that our fabrication method is
      a promising way to fabricate high-efficiency lasers at a low cost.

PMID- 24921336
TI  - Optically controllable THz chiral metamaterials.
AB  - Switchable and tunable chiral metamaterial response is numerically demonstrated
      here in different uniaxial chiral metamaterial structures operating in the THz
      regime. The structures are based on the bi-layer conductor design and the
      tunable/switchable response is achieved by replacing parts of the metallic
      components of the structures by photoconducting Si, which can be transformed from
      an insulating to an almost conducting state through photoexcitation, achievable
      under external optical pumping. All the structures proposed and discussed here
      exhibit frequency regions with giant tunable circular dichroism, as well as
      regions with giant tunable optical activity, showing unique potential in the
      achievement of active THz polarization components, like tunable polarizers and
      polarization filters. 

PMID- 24921338
TI  - Phase regeneration of phase encoded signals by hybrid optical phase squeezer.
AB  - We present a new method to perform phase regeneration of phase encoded signals.
      In our concept called "hybrid optical phase squeezer (HOPS)," a multilevel phase
      quantized signal is synthesized through the coherent addition of a phase
      conjugate copy of the signal and a phase harmonic of the signal with a frequency
      shifter. Unlike the conventional method by phase sensitive amplification, HOPS
      does not use any optical parametric gain such that only optical elements with low
      optical nonlinearity are necessary for optical phase quantization. In the proof
      of-concept experiment, it is confirmed that a 2-level HOPS can perform quadrature
      squeezing with an extinction ratio of 40 dB. Simultaneous phase regeneration of
      two coherent wavelength-division-multiplexed 10.75-Gb/s binary phase-shift keyed
      signals is successfully demonstrated using a 2-level HOPS based on a
      semiconductor optical amplifier. 

PMID- 24921337
TI  - Superresolution microscope image reconstruction by spatiotemporal object
      decomposition and association: application in resolving t-tubule structure in
      skeletal muscle.
AB  - One key factor that limits resolution of single-molecule superresolution
      microscopy relates to the localization accuracy of the activated emitters, which
      is usually deteriorated by two factors. One originates from the background noise
      due to out-of-focus signals, sample auto-fluorescence, and camera acquisition
      noise; and the other is due to the low photon count of emitters at a single
      frame. With fast acquisition rate, the activated emitters can last multiple
      frames before they transiently switch off or permanently bleach. Effectively
      incorporating the temporal information of these emitters is critical to improve
      the spatial resolution. However, majority of the existing reconstruction
      algorithms locate the emitters frame by frame, discarding or underusing the
      temporal information. Here we present a new image reconstruction algorithm based
      on tracklets, short trajectories of the same objects. We improve the localization
      accuracy by associating the same emitters from multiple frames to form tracklets
      and by aggregating signals to enhance the signal to noise ratio. We also
      introduce a weighted mean-shift algorithm (WMS) to automatically detect the
      number of modes (emitters) in overlapping regions of tracklets so that not only
      well-separated single emitters but also individual emitters within multi-emitter
      groups can be identified and tracked. In combination with a maximum likelihood
      estimator method (MLE), we are able to resolve low to medium density of
      overlapping emitters with improved localization accuracy. We evaluate the
      performance of our method with both synthetic and experimental data, and show
      that the tracklet-based reconstruction is superior in localization accuracy,
      particularly for weak signals embedded in a strong background. Using this method,
      for the first time, we resolve the transverse tubule structure of the mammalian
      skeletal muscle. 

PMID- 24921339
TI  - Plasmon modes in single gold nanodiscs.
AB  - Optical properties of single gold nanodiscs were studied by scanning near-field
      optical microscopy. Near-field transmission spectra of a single nanodisc
      exhibited multiple plasmon resonances in the visible to near-infrared region.
      Near-field transmission images observed at these resonance wavelengths show wavy
      spatial features depending on the wavelength of observation. To clarify physical
      pictures of the images, theoretical simulations based on spatial correlation
      between electromagnetic fundamental modes inside and outside of the disc were
      performed. Simulated images reproduced the observed spatial structures excited in
      the disc. Mode-analysis of the simulated images indicates that the spatial
      features observed in the transmission images originate mainly from a few
      fundamental plasmon modes of the disc. 

PMID- 24921340
TI  - Role of heat accumulation on the incubation effect in multi-shot laser ablation
      of stainless steel at high repetition rates.
AB  - We study the incubation effect during laser ablation of stainless steel with
      ultrashort pulses to boost the material removal efficiency at high repetition
      rates. The multi-shot ablation threshold fluence has been estimated for two pulse
      durations, 650-fs and 10-ps, in a range of repetition rates from 50 kHz to 1 MHz.
      Our results show that the threshold fluence decreases with the number of laser
      pulses N due to damage accumulation mechanisms, as expected. Moreover,
      approaching the MHz regime, the onset of heat accumulation enhances the
      incubation effect, which is in turn lower for shorter pulses at repetition rates
      below 600 kHz. A saturation of the threshold fluence value is shown to occur for
      a significantly high number of pulses, and well fitted by a modified incubation
      model.

PMID- 24921341
TI  - Highly coherent mid-IR supercontinuum by self-defocusing solitons in lithium
      niobate waveguides with all-normal dispersion.
AB  - We numerically investigate self-defocusing solitons in a lithium niobate (LN)
      waveguide designed to have a large refractive index (RI) change. The waveguide
      evokes strong waveguide dispersion and all-normal dispersion is found in the
      entire guiding band spanning the near-IR and the beginning of the mid-IR.
      Meanwhile, a self-defocusing nonlinearity is invoked by the cascaded (phase
      mismatched) second-harmonic generation under a quasi-phase-matching pitch.
      Combining this with the all-normal dispersion, mid-IR solitons can form and the
      waveguide presents the first all-nonlinear and solitonic device where no linear
      dispersion (i.e. non-solitonic) regimes exist within the guiding band. Soliton
      compressions at 2 MUm and 3 MUm are investigated, with nano-joule single cycle
      pulse formations and highly coherent octave-spanning supercontinuum generations.
      With an alternative design on the waveguide dispersion, the soliton spectral
      tunneling effect is also investigated, with which few-cycle pico-joule pulses at
      2 MUm are formed by a near-IR pump.

PMID- 24921342
TI  - Experimental demonstration of titanium nitride plasmonic interconnects.
AB  - An insulator-metal-insulator plasmonic interconnect using TiN, a CMOS-compatible
      material, is proposed and investigated experimentally at the telecommunication
      wavelength of 1.55 um. The TiN waveguide was shown to obtain propagation losses
      less than 0.8 dB/mm with a mode size of 9.8 um on sapphire, which agree well with
      theoretical predictions. A theoretical analysis of a solid-state structure using
      Si(3)N(4) superstrates and ultra-thin metal strips shows that propagation losses
      less than 0.3 dB/mm with a mode size of 9 um are attainable. This work
      illustrates the potential of TiN as a realistic plasmonic material for practical
      solid-state, integrated nano-optic and hybrid photonic devices.

PMID- 24921343
TI  - Enhanced light emission from Ge quantum dots in photonic crystal ring resonator.
AB  - Light emitter based on Ge quantum dots embedded in photonic crystal ring
      resonator is designed and fabricated. Six sharp resonant peaks dominate the
      photoluminescence (PL) spectrum ranging from 1500 to 1600 nm at room temperature.
      The light emission enhancement is due to Purcell effect and high collection
      efficiency of the PCRR verified by calculated far-field patterns. The Purcell
      factor of the PCRR is estimated from enhancement factor and increased collection
      efficiency. The linewidth of the emission of a single Ge quantum dot is estimated
      from the Purcell factor.

PMID- 24921344
TI  - Estimation of the number of fluorescent end-members for quantitative analysis of
      multispectral FLIM data.
AB  - Multispectral fluorescence lifetime imaging (m-FLIM) can potentially allow
      identifying the endogenous fluorophores present in biological tissue.
      Quantitative description of such data requires estimating the number of
      components in the sample, their characteristic fluorescent decays, and their
      relative contributions or abundances. Unfortunately, this inverse problem usually
      requires prior knowledge about the data, which is seldom available in biomedical
      applications. This work presents a new methodology to estimate the number of
      potential endogenous fluorophores present in biological tissue samples from time
      domain m-FLIM data. Furthermore, a completely blind linear unmixing algorithm is
      proposed. The method was validated using both synthetic and experimental m-FLIM
      data. The experimental m-FLIM data include in-vivo measurements from healthy and
      cancerous hamster cheek-pouch epithelial tissue, and ex-vivo measurements from
      human coronary atherosclerotic plaques. The analysis of m-FLIM data from in-vivo
      hamster oral mucosa identified healthy from precancerous lesions, based on the
      relative concentration of their characteristic fluorophores. The algorithm also
      provided a better description of atherosclerotic plaques in term of their
      endogenous fluorophores. These results demonstrate the potential of this
      methodology to provide quantitative description of tissue biochemical
      composition. 

PMID- 24921345
TI  - A photonic analog-to-digital converter using phase modulation and self-coherent
      detection with spatial oversampling.
AB  - We propose a new type of photonic analog-to-digital converter (ADC), designed for
      high-resolution (>7 bit) and high sampling rates (scalable to tens of GS/s). It
      is based on encoding the input analog voltage signal onto the phase of an optical
      pulse stream originating from a mode-locked laser, and uses spatial oversampling
      as a means to improve the conversion resolution. This paper describes the concept
      of spatial oversampling and draws its similarities to the commonly used temporal
      oversampling. The design and fabrication of a LiNbO(3)/silica hybrid photonic
      integrated circuit for implementing the spatial oversampling is shown, and its
      abilities are demonstrated experimentally by digitizing gigahertz signals
      (frequencies up to 18GHz) at an undersampled rate of 2.56GS/s with a conversion
      resolution of up to 7.6 effective bits. Oversampling factors of 1-4 are
      demonstrated.

PMID- 24921346
TI  - Optical stacking of microparticles in a pyramidal structure created with a
      symmetric cubic phase.
AB  - We show a simple way to generate three dimensional optical potentials consisting
      of tightly localized high intensity spots arranged in a structure with a
      pyramidal geometry. The three dimensional patterns are created by focusing a
      Gaussian beam with a symmetric cubic phase abs((ax)3) + abs((ay)3) imprinted by a
      spatial light modulator. We show that it is possible to trap and stack around a
      hundred dielectric microspheres (silica mean diameter 2.47 MUm) in pyramidal
      structures (characteristic dimensions H, W ~ 15 - 20MUm) held together by optical
      binding with moderate laser power (P < 20 mW). Axial stability is mainly provided
      by balancing the light scattering force with the axial gradient and gravity. The
      microparticle structures are sufficiently stable to be easily displaced by moving
      the microscope stage.

PMID- 24921347
TI  - A low-power, high-speed, 9-channel germanium-silicon electro-absorption modulator
      array integrated with digital CMOS driver and wavelength multiplexer.
AB  - We demonstrate the first germanium-silicon C-band electro-absorption based
      waveguide modulator array and echelle-grating-based silicon wavelength
      multiplexer integrated with a digital CMOS driver circuit. A 9-channel, 10Gbps
      SiGe electro-absorption wavelength-multiplexed modulator array consumed a power
      of 5.8mW per channel while being modulated at 10.25Gbps by 40nm CMOS drivers
      delivering peak-to-peak voltage swings of 2V, achieving a modulation energy
      efficiency of ~570fJ/bit including drivers. Performance up to 25Gbps on a single
      channel SiGe modulator and CMOS driver is also reported.

PMID- 24921348
TI  - Theoretical investigation of the more suitable rare earth to achieve high gain in
      waveguide based on silica containing silicon nanograins doped with either Nd3+ or
      Er3+ ions.
AB  - We present a comparative study of the gain achievement in a waveguide whose
      active layer is constituted by a silica matrix containing silicon nanograins
      acting as sensitizer of either neodymium ions (Nd3+) or erbium ions (Er3+). By
      means of an auxiliary differential equation and finite difference time domain
      (ADE-FDTD) approach that we developed, we investigate the steady states regime of
      both rare earths ions and silicon nanograins levels populations as well as the
      electromagnetic field for different pumping powers ranging from 1 to 104 mW/mm2.
      Moreover, the achievable gain has been estimated in this pumping range. The Nd3+
      doped waveguide shows a higher gross gain per unit length at 1064 nm (up to 30
      dB/cm) than the one with Er3+ doped active layer at 1532 nm (up to 2 dB/cm).
      Taking into account the experimental background losses we demonstrate that a
      significant positive net gain can only be achieved with the Nd3+ doped waveguide.

PMID- 24921349
TI  - Guided-mode resonant polarization-controlled tunable color filters.
AB  - We demonstrate efficient guided-mode resonant polarization-controlled tunable
      color filters. The devices consist of subwavelength gratings that are partially
      etched into a thin silicon-nitride film deposited on a glass substrate. Two color
      filters with grating periods of 300 nm and 370 nm are designed and fabricated.
      The 300-nm device exhibits green and blue colors and the 370-nm device generates
      red and yellow colors for TE and TM polarization, respectively. The pixels have a
      spectral bandwidth of ~12 nm with efficiencies exceeding 90% for TE polarization
      and 80% for TM polarization. The devices may find application in displays, image
      sensors, and biomedical imaging technologies. 

PMID- 24921350
TI  - Three-dimensional organic microlasers with low lasing thresholds fabricated by
      multiphoton and UV lithography.
AB  - Cuboid-shaped organic microcavities containing a pyrromethene laser dye and
      supported upon a photonic crystal have been investigated as an approach to
      reducing the lasing threshold of the cavities. Multiphoton lithography
      facilitated fabrication of the cuboid cavities directly on the substrate or on
      the decoupling structure, while similar structures were fabricated on the
      substrate by UV lithography for comparison. Significant reduction of the lasing
      threshold by a factor of ~30 has been observed for cavities supported by the
      photonic crystal relative to those fabricated on the substrate. The lasing mode
      spectra of the cuboid microresonators provide strong evidence showing that the
      lasing modes are localized in the horizontal plane, with the shape of an
      inscribed diamond. 

PMID- 24921351
TI  - Low power super resolution fluorescence microscopy by lifetime modification and
      image reconstruction.
AB  - We demonstrate a new method for obtaining sub-diffraction resolution in
      fluorescence microscopy. The technique involves the analysis of the time
      evolution of fluorescence images in the presence of weak and unstructured
      (fundamental Gaussian) continuous wave stimulated emission depletion. A reduced
      point spread functions (PSF) is obtained by the recombination of time segments of
      the evolving image. A significant reduction in the PSF for 20 nm fluorescent
      beads (ca. 240 nm to 125 nm) is obtained with an on-sample power of 7.5 mW (17
      MW/cm2) - substantially lower than that required for spatially structured
      stimulated emission depletion microscopy.

PMID- 24921352
TI  - Imaging dark objects with intensity interferometry.
AB  - We have developed a technique for imaging dark, i.e. non-radiating, objects by
      intensity interferometry measurements using a thermal light source in the
      background. This technique is based on encoding the dark object's profile into
      the spatial coherence of such light. We demonstrate the image recovery using an
      adaptive error-minimizing Gerchberg-Saxton algorithm in case of a completely
      opaque object, and outline the steps for imaging purely refractive objects. 

PMID- 24921353
TI  - Design and fabrication of broadband guided-mode resonant reflectors in TE
      polarization.
AB  - We present the design and fabrication of guided-mode resonant broadband
      reflectors operating in transverse electric (TE) polarization. The structure
      consists of a subwavelength one-dimensional grating with a two-part period and a
      nanometric homogeneous layer of amorphous silicon on a quartz substrate. A
      representative reflector exhibits 99% reflectance over a 380-nm spectral range
      spanning 1440-1820 nm. The fabrication involves thin-film deposition,
      interferometric lithography, and reactive ion etching. Experimental reflectance
      greater than 90% is achieved over a ~360-nm bandwidth. The spectral bandwidths
      demonstrated exceed formerly reported results for two-part periodic resonators
      working in TE polarization. 

PMID- 24921354
TI  - Photonic molecules: tailoring the coupling strength and sign.
AB  - We demonstrate a large tuning of the coupling strength in Photonic Crystal
      molecules without changing the inter-cavity distance. The key element for the
      design is the "photonic barrier engineering", where the "potential barrier" is
      formed by the air-holes in between the two cavities. This consists in changing
      the hole radius of the central row in the barrier. As a result we show, both
      numerically and experimentally, that the wavelength splitting in two evanescently
      coupled Photonic Crystal L3 cavities (three holes missing in the GammaK direction
      of the underlying triangular lattice) can be continuously controlled up to 5* the
      initial value upon ~ 30% of hole-size modification in the barrier. Moreover, the
      sign of the splitting can be reversed in such a way that the fundamental mode can
      be either the symmetric or the anti-symmetric one without altering neither the
      cavity geometry nor the inter-cavity distance. Coupling sign inversion is
      explained in the framework of a Fabry-Perot model with underlying propagating
      Bloch modes in coupled W1 waveguides. 

PMID- 24921355
TI  - Hyperbolic geometry for colour metrics.
AB  - It is well established from both colour difference and colour order perpectives
      that the colour space cannot be Euclidean. In spite of this, most colour spaces
      still in use today are Euclidean, and the best Euclidean colour metrics are
      performing comparably to state-of-the-art non-Euclidean metrics. In this paper,
      it is shown that a transformation from Euclidean to hyperbolic geometry (i.e.,
      constant negative curvature) for the chromatic plane can significantly improve
      the performance of Euclidean colour metrics to the point where they are
      statistically significantly better than state-of-the-art non-Euclidean metrics on
      standard data sets. The resulting hyperbolic geometry nicely models both
      qualitatively and quantitatively the hue super-importance phenomenon observed in
      colour order systems. 

PMID- 24921356
TI  - Discrete photonics resonator in coupled waveguide arrays.
AB  - We demonstrate both theoretically and experimentally that discrete diffraction
      resonance can be designed, fabricated, and successfully probed in functionalized 
      guidonic - coupled waveguide arrays. We evidence that double-barrier patterning
      of the coupling creates wavelength-independent angular tunnel resonance in the
      transmitted and the reflected intensity of light beams freely propagating in the
      plane of the array. Transmission peaks obtained are associated with resonant
      excitation of the engineered array bound supermodes of the functionalized array,
      in agreement with accurate and practical numerical modeling based on extended
      coupled-mode theory. The linear operation of the guidonic resonant tunneling
      double barrier makes up an original resonator for discrete photonics, suitable
      for all-optical control of light. 

PMID- 24921357
TI  - Enhancement of light extraction efficiency of OLEDs using Si3N4-based optical
      scattering layer.
AB  - An optical scattering layer, consisting of a Si3N4 nano-pillar array and a spin
      coated hydrogen silsesquioxane (HSQ) planarization layer, was introduced to an
      organic light-emitting diode (OLED) substrate to increase the out-coupling
      efficiency. After plasma enhanced chemical vapor deposition (PECVD) of the Si3N4
      layer, the nano-pillar array was created using nanoimprint lithography and
      reactive ion etching. As the Si3N4 pillar array has a refractive index of 2.0,
      photons generated in the organic layer are scattered by the Si3N4 structures and
      thus have a higher chance of being emitted from the device. The spin-coated HSQ
      planarization layer produces a flat substrate, which is essential for depositing
      a uniform organic material layer and assuring the electric conductivity of the
      transparent conducting oxide (TCO) layer. In this study, Si3N4 nano-structures
      with a height of 100 or 300 nm were used to enhance the out-coupling efficiency
      of the OLED devices. Although the electrical conductivity of the TCO layer
      deposited on the light scattering layer was slightly degraded, the OLED devices
      formed with the light scattering layer exhibited a higher luminous power at given
      electrical power. Consequently, the use of a planarized 300-nm-thick Si3N4 layer
      increased the external quantum efficiency of the OLED device by 50% at 10,000
      cd/m2 compared to the reference OLED device fabricated on a flat glass substrate.

PMID- 24921358
TI  - Fast, super resolution imaging via Bessel-beam stimulated emission depletion
      microscopy.
AB  - A substantial advantage of stimulated emission depletion (STED) microscopy over
      other super-resolution methods is that images can be acquired in real-time
      without any post-processing. However imaging speed and photodamage are two major
      concerns for STED imaging of whole cells. Here we propose a new microscopy method
      we have termed Bessel-Beam STED (or BB-STED) that overcomes both of these
      limitations of conventional STED microscopy. In the proposed method, rather than
      exciting a single STED spot in the sample, an entire line of the sample is
      illuminated. This line-scanning technique dramatically increases the speed of
      STED. In addition, plane-illumination by scanning of the line across the focal
      plane of a detection objective limits the light to a thin layer of the sample and
      thus significantly reduces photobleaching and photodamage above and below the
      focal plane compared to epi-illumination. Using the organic dye Atto647N as an
      example, we calculated the STED power required to break the diffraction limit.
      The results presented here will be used to guide future experimental designs. 

PMID- 24921359
TI  - Modeling of optomechanical coupling in a phoxonic crystal cavity in diamond.
AB  - A photonic and phononic crystal (phoxonic crystal PxC) is a periodically
      patterned material that can at the same time localize optical and mechanical
      modes. Here we theoretically model one-dimensional PxC in diamond and find high
      quality mechanical resonances with very high frequencies > 10 GHz and optical
      properties comparable to those of PxC in other materials. The simultaneous
      confinement of photons and phonons leads to an optomechanical interaction that we
      calculate in a perturbation approach. The optomechanical coupling strengths reach
      values in the MHz range. We identify design rules to simultaneously achieve high
      optical and mechanical quality factors along with strong optomechanical coupling.

PMID- 24921360
TI  - Spoof polariton enhanced modal density of states in planar nanostructured
      metallic cavities.
AB  - Spoof surface modes on nanostructured metallic surfaces are known to have
      tailorable dispersion dependent on the geometric characteristics of the periodic
      pattern. Here we examine the spoof plasmon dispersion on an isolated grating and
      a grating-planar mirror cavity configuration. The spoof polariton dispersion in
      the cavity is obtained using the scattering matrix approach, and the related
      differential modal density of states is introduced to obtain the mode dispersion
      and classify the cavity polariton modes. The grating-mirror cavity geometry is an
      example of periodically nanostructured metals above a planar ground plane. The
      properties discussed here are relevant for applications ranging from thin
      electromagnetic perfect absorbers to near-field radiative heat transfer. 

PMID- 24921361
TI  - Assessing the stability of an ALPAO deformable mirror for feed-forward operation.
AB  - A deformable mirror (DM) is a mirror whose surface can be deformed in order to
      correct for optical aberrations. If a DM is used in a feed-forward operation
      (i.e. without feed-back, also known as open-loop) it is, among other
      requirements, crucial that a set of actuator commands repeatedly results in the
      same surface shape. We have tested an ALPAO DM against this criterion, by
      repeatedly applying a set of actuator commands over hours and monitoring the DM
      shape with an interferometer. We found that if the surface shape was held to
      shape A for several hours, then changed to a second shape, B, the DM surface will
      drift from this new shape over the course of several hours. During this period
      the root-mean-square (RMS) of the deviation from shape B can exceed 30% of the
      RMS of the difference between shapes A and B. This can correspond to a surface
      deviation with RMS of several hundred nanometers, and would severely impact the
      resulting performance of an AO system using such a DM in a feed-forward
      operation. We have developed a model to correct for the time-varying surface
      shape in software by continuously adapting the actuator commands over the
      stabilization period. Application of the stabilisation procedure allows the
      surface to remain stable to within 4 nm RMS after a period of 6 minutes. We also
      provide a suggestion on how to improve the repeatability of surface response to
      different sets of actuator commands, which can be affected by the surface drift.

PMID- 24921362
TI  - Near infrared amplified spontaneous emission in a dye-doped polymeric waveguide
      for active plasmonic applications.
AB  - Near-infrared amplified spontaneous emission (ASE) from an optically-pumped dye
      doped polymeric slab waveguide, consisting of IR-140 in PMMA on a glass
      substrate, has been characterised. The ASE gain was measured using the variable
      stripe length method. Linewidth narrowing with increasing pump intensity was
      observed, indicating ASE gain in this material. The effects of the dye
      concentration and pump intensity on the gain were investigated under linear
      operation. The maximum achieved gain coefficient is gamma ~68 cm(-1) for a film
      with 0.8 wt % of IR-140 to PMMA for a pump intensity of 43.4 mJ/cm(2). The
      polarisation dependence of the ASE gain was also investigated by measuring the
      gain coefficient of orthogonal TE and TM modes and varying the pump polarisation
      relative to the amplifier length. It was observed that there is some degree of
      gain anisotropy when the pump polarisation is aligned perpendicular to the
      length, but that the gain was isotropic when the pump polarisation is aligned
      parallel the length. The applicability of IR-140 doped PMMA for active plasmonic
      applications is discussed.

PMID- 24921363
TI  - Sub-50-fs pulse generation from thulium-doped ZBLAN fiber laser oscillator.
AB  - An ultrafast, passively mode-locked fiber laser oscillator has been realized
      using thulium-doped ZBLAN fibers. Very low dispersion of ZBLAN glass fibers
      enabled generation of pulses with broad spectra extending from 1730 nm to 2050
      nm. Pulses are obtained with the average power of 13 mW at the repetition rate of
      67.5 MHz when the pump power is 140 mW. The output pulses are compressed with a
      pair of SF10 prisms and their durations are measured with SHG FROG, from which we
      obtained the pulse duration as short as 45 fs. 

PMID- 24921364
TI  - Polarization-insensitive wavelength conversion of 40 Gb/s NRZ-DPSK signals in a
      silicon polarization diversity circuit.
AB  - Polarization insensitive wavelength conversion of a 40 Gb/s non-return-to-zero
      (NRZ) differential phase-shift keying (DPSK) data signal is demonstrated using
      four-wave mixing (FWM) in a silicon nanowire circuit. Polarization independence
      is achieved using a diversity circuit based on polarization rotators and
      splitters, which is fabricated by a simple process on the silicon-on-insulator
      (SOI) platform. Error-free performance is achieved with only 0.5 dB of power
      penalty compared to the wavelength conversion of a signal with well optimized
      input polarization. Additionally, data transmission over 161 km standard single
      mode fiber (SSMF) is demonstrated at 40 Gb/s using optical phase conjugation
      (OPC) in the proposed circuit. 

PMID- 24921365
TI  - Ultra-broadband THz time-domain spectroscopy of common polymers using THz air
      photonics.
AB  - Terahertz-range dielectric properties of the common polymers low-density
      polyethylene (LDPE), cyclic olefin/ethylene copolymer (TOPAS(r)), polyamide-6
      (PA6), and polytetrafluoroethylene (PTFE or Teflon(r)) are characterized in the
      ultra-broadband frequency window 2-15 THz, using a THz time-domain spectrometer
      employing air-photonics for the generation and detection of single-cycle sub-50
      fs THz transients. The time domain measurements provide direct access to both the
      absorption and refractive index spectra. The polymers LDPE and TOPAS(r)
      demonstrate negligible absorption and spectrally-flat refractive index across the
      entire spectroscopy window, revealing the high potential of these polymers for
      applications in THz photonics such as ultra-broadband polymer-based dielectric
      mirrors, waveguides, and fibers. Resonant high-frequency polar vibrational modes
      are observed and assigned in polymers PA6 and PTFE, and their dielectric
      functions in the complete frequency window 2-15 THz are theoretically reproduced.
      Our results demonstrate the potential of ultra-broadband air-photonics-based THz
      time domain spectroscopy as a valuable analytic tool for materials science.

PMID- 24921366
TI  - Effects of dielectric thickness on optical behavior and tunability of one
      dimensional Ag/SiO2 multilayered metamaterials.
AB  - We fabricated one-dimensional periodic multilayered metamaterial structures
      consisting of Ag and SiO2alternating layers. Optical responses, such as
      transmission and absorption, are consistent well within finite difference time
      domain (FDTD) simulations. Angle dependent real and imaginary dielectric
      permittivity reflection spectra demonstrate their operational capability in the
      visible wavelength region. This multilayer metamaterial can be converted into a
      photonic crystal by manipulating the thickness of SiO2 and we demonstrate that
      proper filling of SiO2/Ag layers the operating wavelength can be tuned to higher
      wavelength region. However, absolute value of transmission reduces with
      increasing number of multilayer pairs due to metal absorption.

PMID- 24921367
TI  - Bandwidth-tunable optical spatial filters with nanoparticle arrays.
AB  - Modeling a nanoparticle array (NPA) inside a thin glass slab as a lumped optical
      resonator, we propose a systematic approach to design for an efficient optical
      filter with bandwidth tunability. The quality factor and bandwidth of the
      resonator are related to the physical, geometrical, and electrical parameters of
      an NPA and its surrounding medium, whose permittivity is varied to change the
      bandwidth. We propose a structure amenable to our design approach consisting of
      an NPA slab surrounded by liquid crystal whose permittivity can be altered. We
      validate the design procedure with examples of tunable-bandwidth filters at
      different frequency regimes from NIR to blue. 

PMID- 24921368
TI  - A high transmittance color liquid crystal display mode with controllable color
      gamut and transparency.
AB  - In this paper, we propose a color transparent liquid crystal (LC) mode that can
      control the properties of the color gamut and transparency in a single panel. To
      achieve high transmittance in the transparent LC mode, a reactive mesogen (RM)
      with embedded color dichroic dyes was applied instead of a color filter.
      Basically, the LC mode applied a 3-terminal electrode structure to switch between
      the transparent LC mode and the conventional color LC mode. Depending on the
      direction of the applied voltage, we can operate both the color mode and the
      transparent mode in a single panel, and modulate the transparency and color
      purity of the cell through appropriate voltage control. In the experiments, we
      confirmed that the transmittance and the color gamut of the cell were 39.4% and
      2% in the transparent LC mode and 14.9% and 34% in the color LC mode,
      respectively. Modulation of the color gamut and transparency between each LC mode
      are also demonstrated in the paper. 

PMID- 24921369
TI  - Ptychographic microscope for three-dimensional imaging.
AB  - Ptychography is a coherent imaging technique that enables an image of a specimen
      to be generated from a set of diffraction patterns. One limitation of the
      technique is the assumption of a multiplicative interaction between the
      illuminating coherent beam and the specimen, which restricts ptychography to
      samples no thicker than a few tens of micrometers in the case of visible-light
      imaging at micron-scale resolution. By splitting a sample into axial sections, we
      demonstrated in recent work that this thickness restriction can be relaxed and
      whats-more, that coarse optical sectioning can be realized using a single
      ptychographic data set. Here we apply our technique to data collected from a
      modified optical microscope to realize a reduction in the optical sectioning
      depth to 2 MUm in the axial direction for samples up to 150 MUm thick.
      Furthermore, we increase the number of sections that are imaged from 5 in our
      previous work to 34 here. Our results compare well with sectioned images
      collected from a confocal microscope but have the added advantage of strong phase
      contrast, which removes the need for sample staining.

PMID- 24921370
TI  - Coherent perfect absorption and transparency in a nanostructured graphene film.
AB  - We show numerically that both coherent perfect absorption and transparency can be
      realized in a monolayer graphene. The graphene film, doped and patterned with a
      periodical array of holes, can support plasmonic resonances in the Mid-infrared
      range. Under the illumination of two counter-propagating coherent optical beams,
      resonant optical absorption may be tuned continuously from 99.93% to less than
      0.01% by controlling their relative phase which gives a modulation contrast of 40
      dB (about 30 dB for transmission). The phenomenon provides a versatile platform
      for manipulating the interaction between light and graphene and may serve
      applications in optical modulators, transducers, sensors and coherent detectors. 

PMID- 24921371
TI  - Identification of wheat quality using THz spectrum.
AB  - The terahertz (THz) spectra in the range of 0.2-1.6 THz (6.6-52.8 cm<sup>
      1</sup>) of wheat grains with various degrees of deterioration (normal, worm
      eaten, moldy, and sprouting wheat grains) were investigated by terahertz time
      domain spectroscopy. Principal component analysis (PCA) was employed to extract
      feature data according to the cumulative contribution rates; the top four
      principal components were selected, and then a support vector machine (SVM)
      method was applied. Several selection kernels (linear, polynomial, and radial
      basis functions) were applied to identify the four types of wheat grain. The
      results showed that the materials were identified with an accuracy of nearly 95%.
      Furthermore, this approach was compared with others (principal component
      regression, partial least squares regression, and back-propagation neural
      networks). The comparisons showed that PCA-SVM outperformed the others and also
      indicated that the proposed method of THz technology combined with PCA-SVM is
      efficient and feasible for identifying wheat of different qualities. 

PMID- 24921372
TI  - Microstructured gradient-index antireflective coating fabricated on a fiber tip
      with direct laser writing.
AB  - We present a simple broadband gradient-index antireflective coating, fabricated
      directly on a single mode telecom fiber tip. A regular array of hemi-ellipsoidal
      protrusions significantly reduce the Fresnel reflection from the glass-air
      interface. The parameters of the structure were optimized with numerical
      simulation for the best performance at and around 1550 nm and the coating was
      fabricated with Direct Laser Writing. The measured reflectance decreased by a
      factor of 30 at 1550 nm and was below 0.28% for the 100 nm spectral band around
      the central wavelength. Compared to quarter wavelength antireflective coatings
      the demonstrated approach offers significantly reduced technological challenges,
      in particular processing of a single optical material with low sensitivity to
      imperfections in the fabrication process. 

PMID- 24921373
TI  - Antenna gain of actively compensated free-space optical communication systems
      under strong turbulence conditions.
AB  - Current Strehl ratio models for actively compensated free-space optical
      communications terminals do not accurately predict system performance under
      strong turbulence conditions as they are based on weak turbulence theory. For
      evaluation of compensated systems, we present an approach for simulating the
      Strehl ratio with both low-order (tip/tilt) and higher-order (adaptive optics)
      correction. Our simulation results are then compared to the published models and
      their range of turbulence validity is assessed. Finally, we propose a new Strehl
      ratio model and antenna gain equation that are valid for general turbulence
      conditions independent of the degree of compensation. 

PMID- 24921374
TI  - Generation of multipartite continuous-variable entanglement via atomic spin wave:
      Heisenberg-Langevin approach.
AB  - We conduct theoretical studies on the effects of various parameters on generation
      of multipartite continuous-variable entanglement via atomic spin wave induced by
      the strong coupling and probe fields in the Lambda-type electromagnetically
      induced transparency configuration in a realistic atomic ensemble by using the
      Heisenberg-Langevin formalism. It is shown that the increase of the atomic
      density and/or Rabi frequencies of the scattering fields, as well as the decrease
      of the coherence decay rate of the lower doublet would strengthen the degree of
      multipartite entanglement. This provides a clear evidence that the creation of
      multicolor multipartite entangled narrow-band fields to any desired number with a
      long correlation time can be achieved conveniently by using atomic spin wave in
      an atomic ensemble with large optical depth, which may find interesting
      applications in quantum information processing and quantum networks. 

PMID- 24921375
TI  - Junction-less phototransistor with nanowire channels, a modeling study.
AB  - We propose a new nanowire based, junction-less phototransistor, that consists of
      a channel with both wide and narrow regions to ensure efficient light absorption
      and low dark current, respectively. While the light is absorbed in the wide
      region, the narrow region allows for ease of band engineering. We also find that
      a nanowire in the source can further boost the optical gain. The proposed device,
      which can potentially detect very low light intensities, does not rely on
      complicated doping profiles, but instead uses suitably designed gates. Our
      calculations show the detection of a photon flux as low as 35 per second. 

PMID- 24921376
TI  - Design and optimization of a parallel spectrometer for ultra-fast X-ray science.
AB  - In the present work, different varied line space (VLS) and reflection zone plate
      (RZP) gratings are analyzed for their suitability in low-signal femtosecond soft
      X-ray spectroscopy. The need for high efficiency suggests a straightened focal
      line whose sharpness and residual curvature will determine the quality. One- and
      two-dimensional VLS structures feature an attractive trade-off between a
      sufficient optical performance and a strongly relaxed fabrication, due to
      moderate line densities which are easily accessible by e-beam lithography. Based
      on fanned-out RZP arrays, their continuous limit version is identified to
      generate an almost perfect focal line however, with an aberration level three
      orders of magnitude better than for the VLS gratings and well below the
      diffraction limit over large acceptance angles. 

PMID- 24921377
TI  - Enpolarization and depolarization of light scattered from chromatic complex
      media.
AB  - Influence of the variations of the scattering properties of a disordered medium
      with respect to frequency on the polarization of scattered light is investigated.
      We focus on the strongly scattering regime with the sum of random phasors
      scattering model that is extended to chromatic media and made frequency
      sensitive. It is numerically shown how the scattered polarization depends on the
      incident polarization and the incident light bandwidth to scattering coefficients
      chromatic length ratio. Under the presented approach, both phenomena of
      depolarization and enpolarization of light appear unified. 

PMID- 24921378
TI  - Universal method for constructing N-port non-blocking optical router based on 2 *
      2 optical switch for photonic networks-on-chip.
AB  - We propose a universal method for constructing N-port non-blocking optical router
      for photonic networks-on-chip, in which all microring (MR) optical switches or
      Mach-Zehnder (M-Z) optical switches behave as 2 * 2 optical switches. The optical
      router constructed by the proposed method has minimum optical switches, in which
      the number of the optical switches is reduced about 50% compared to the reported
      optical routers based on MR optical switches and more than 30% compared to the
      reported optical routers based on M-Z optical switches, and therefore is more
      compact in footprint and more power-efficient. We also present a strict
      mathematical proof of the non-blocking routing of the proposed N-port optical
      router.

PMID- 24921379
TI  - A high-speed, tunable silicon photonic ring modulator integrated with ultra
      efficient active wavelength control.
AB  - We report the first complete 10G silicon photonic ring modulator with integrated
      ultra-efficient CMOS driver and closed-loop wavelength control. A selective
      substrate removal technique was used to improve the ring tuning efficiency.
      Limited by the thermal tuner driver output power, a maximum open-loop tuning
      range of about 4.5nm was measured with about 14mW of total tuning power including
      the heater driver circuit power consumption. Stable wavelength locking was
      achieved with a low-power mixed-signal closed-loop wavelength controller. An
      active wavelength tracking range of > 500GHz was demonstrated with controller
      energy cost of only 20fJ/bit. 

PMID- 24921380
TI  - Optimization of overlap uniformness for ptychography.
AB  - We demonstrate the advantages of imaging with ptychography scans that follow a
      Fermat spiral trajectory. This scan pattern provides a more uniform coverage and
      a higher overlap ratio with the same number of scan points over the same area
      than the presently used mesh and concentric [13] patterns. Under realistically
      imperfect measurement conditions, numerical simulations show that the quality of
      the reconstructed image is improved significantly with a Fermat spiral compared
      with a concentric scan pattern. The result is confirmed by the performance
      enhancement with experimental data, especially under low-overlap conditions.
      These results suggest that the Fermat spiral pattern increases the quality of the
      reconstructed image and tolerance to data with imperfections. 

PMID- 24921381
TI  - Refractive index sensor based on the leaky radiation of a microfiber.
AB  - In this work we present a refractive index sensor based on the leaky radiation of
      a microfiber. The 5.3um diameter microfiber is fabricated by drawing a commercial
      optical fiber. When the microfiber is immersed into a liquid with larger
      refractive index than the effective index of fiber mode, the light will leak out
      through the leaky radiation process. The variation of refractive index of liquid
      can be monitored by measuring radiation angle of light. The refractive index
      sensitivity can be over 400 degree/RIU in theory. In the experiment, the
      variation value 0.001 of refractive index of liquid around this microfiber can be
      detected through this technique. This work provides a simple and sensitive method
      for refractive index sensing application. 

PMID- 24921382
TI  - Rigorous microlens design using vector electromagnetic method combined with
      simulated annealing optimization.
AB  - In this paper, finite-aperture diffractive optical element with its critical
      dimension smaller than illumination wavelength is modeled and optimized using an
      integrated method. This method employs rigorous analysis model based on Finite
      Difference Time Domain (FDTD), and simulated annealing (SA) global search
      algorithm. Numerical results reveal that the diffraction efficiency of the 8-step
      microlens quickly climbs to its global optimum along with the optimization
      process, which manifests its global search ability. The design algorithm and
      implementation are discussed in details. Considering its time consuming
      efficiency and global search ability, our method provides valuable reference
      value in practical multistep microlens design. 

PMID- 24921383
TI  - Stepwise angular spectrum method for curved surface diffraction.
AB  - We present a method to calculate wave propagation between arbitrary curved
      surfaces using a staircase approximation approach. The entire curved surface is
      divided into multiple subregions and each curved subregion is approximated by a
      piecewise flat subplane allowing the application of conventional diffraction
      theory. In addition, in order to reflect the local curvature of each subregion,
      we apply the phase compensation technique. Analytical expressions are derived
      based on the angular spectrum method and numerical studies are conducted to
      validate our method. 

PMID- 24921384
TI  - Time domain multiplexed spatial division multiplexing receiver.
AB  - A novel time domain multiplexed (TDM) spatial division multiplexing (SDM)
      receiver which allows for the reception of >1 dual polarization mode with a
      single coherent receiver, and corresponding 4-port oscilloscope, is
      experimentally demonstrated. Received by two coherent receivers and respective 4
      port oscilloscopes, a 3 mode transmission of 28GBaud QPSK, 8, 16, and 32QAM over
      41.7km of few-mode fiber demonstrates the performance of the TDM-SDM receiver
      with respect to back-to-back. In addition, by using carrier phase estimation
      employing one digital phase locked loop per output, the frequency offset between
      the transmitter laser and local oscillator is shown to perform similar to
      previous work which employs 3 coherent receivers and 4-port oscilloscopes which
      are dedicated to the reception of each the three modes. 

PMID- 24921385
TI  - Plasmon hybridization in pyramidal metamaterials: a route towards ultra-broadband
      absorption.
AB  - Pyramidal metamaterials are currently developed for ultra-broadband absorbers.
      They consist of periodic arrays of alternating metal/dielectric layers forming
      truncated square-based pyramids. The metallic layers of increasing lengths play
      the role of vertically and, to a less extent, laterally coupled plasmonic
      resonators. Based on detailed numerical simulations, we demonstrate that plasmon
      hybridization between such resonators helps in achieving ultra-broadband
      absorption. The dipolar modes of individual resonators are shown to be prominent
      in the electromagnetic coupling mechanism. Lateral coupling between adjacent
      pyramids and vertical coupling between alternating layers are proven to be key
      parameters for tuning of plasmon hybridization. Following optimization, the
      operational bandwidth of Au/Ge pyramids, i.e. the bandwidth within which
      absorption is higher than 90%, extends over a 0.2-5.8 um wavelength range, i.e.
      from UV-visible to mid-infrared, and total absorption (integrated over the
      operational bandwidth) amounts to 98.0%. The omni-directional and polarization
      independent high-absorption properties of the device are verified. Moreover, we
      show that the choice of the dielectric layer material (Si versus Ge) is not
      critical for achieving ultra-broadband characteristics, which confers versatility
      for both design and fabrication. Realistic fabrication scenarios are briefly
      discussed. This plasmon hybridization route could be useful in developing
      photothermal devices, thermal emitters or shielding devices that dissimulate
      objects from near infrared detectors. 

PMID- 24921386
TI  - Direct-writing of complex liquid crystal patterns.
AB  - We report on a direct-write system for patterning of arbitrary, high-quality,
      continuous liquid crystal (LC) alignment patterns. The system uses a focused UV
      laser and XY scanning stages to expose a photoalignment layer, which then aligns
      a subsequent LC layer. We intentionally arrange for multiple overlapping
      exposures of the photoalignment material by a scanned Gaussian beam, often with a
      plurality of polarizations and intensities, in order to promote continuous and
      precise LC alignment. This type of exposure protocol has not been well
      investigated, and sometimes results in unexpected LC responses. Ultimately, this
      enables us to create continuous alignment patterns with feature sizes smaller
      than the recording beam. We describe the system design along with a thorough
      mathematical system description, starting from the direct-write system inputs and
      ending with the estimated alignment of the LC. We fabricate a number of test
      patterns to validate our system model, then design and fabricate a number of
      interesting well-known elements, including a q-plate and polarization grating. 

PMID- 24921387
TI  - An adaptive scaling and biasing scheme for OFDM-based visible light communication
      systems.
AB  - Orthogonal frequency-division multiplexing (OFDM) has been widely used in visible
      light communication systems to achieve high-rate data transmission. Due to the
      nonlinear transfer characteristics of light emitting diodes (LEDs) and owing the
      high peak-to-average-power ratio of OFDM signals, the transmitted signal has to
      be scaled and biased before modulating the LEDs. In this contribution, an
      adaptive scaling and biasing scheme is proposed for OFDM-based visible light
      communication systems, which fully exploits the dynamic range of the LEDs and
      improves the achievable system performance. Specifically, the proposed scheme
      calculates near-optimal scaling and biasing factors for each specific OFDM symbol
      according to the distribution of the signals, which strikes an attractive trade
      off between the effective signal power and the clipping-distortion power. Our
      simulation results demonstrate that the proposed scheme significantly improves
      the performance without changing the LED's emitted power, while maintaining the
      same receiver structure. 

PMID- 24921389
TI  - Transforming growth factor-beta1 regulates the telomerase reverse transcriptase
      in rat hepatic stellate cells.
AB  - OBJECTIVE: To determine the effect of transforming growth factor-beta1 (TGF
      beta1) on the expression of telomerase in hepatic stellate cells (HSCs) in rats
      and the role of TGF-beta1 in the development of liver fibrosis. METHODS: Primary
      HSCs were isolated from normal rats by density gradient separation and divided
      into 2 groups for culturing. The morphology of HSCs was identified by the
      inverted fluorescence microscope. The purity of HSCs was identified by
      immunohistological expression and fluorescence analysis. One group of HSCs was
      treated with different concentrations (0, 0.1, 1, and 10 ng/mL) of TGF-beta1 for
      24 h, while the other group was treated with 1 ng/mL TGF-beta1 and cultured for
      3, 6, and 9 days. The mRNA expression of telomerase reverse transcriptase (TERT)
      was assessed and compared by polymerase chain reaction. RESULTS: Cell morphology
      showed that TGF-beta1 triggered the differentiation of HSCs from a quiescent
      phenotype into highly activated myofibroblasts. TERT mRNA expression in the
      primary HSCs showed slight increase with the culture time, though with no
      statistical difference between the results at various time points (P>0.05). TGF
      beta1 at 0.1 ng/mL did not significantly affect the TERT mRNA level compared with
      the 0 ng/mL group, while 1 ng/mL and 10 ng/mL TGF-beta1 significantly decreased
      the level of TERT mRNA (P<0.05). TGF-beta1 at 1 ng/mL had only weak effect on
      TERT mRNA expression after the 3 day treatment compared with the 0 ng/mL group
      (P>0.05). TGF-beta1 at 1 ng/mL significantly inhibited TERT mRNA expression 6
      days after the treatment (P<0.05). TGF-beta1 inhibited the expression of TERT
      mRNA level in the HSCs in both dose- and time-dependent manner. CONCLUSION: TGF
      beta1 may contribute to the transdifferentiation of HSCs by reducing TERT levels
      to develop hepatic fibrosis.

PMID- 24921390
TI  - Association between two functional SNPs of SCN1A gene and efficacy of
      carbamazepine monotherapy for focal seizures in Chinese Han epileptic patients.
AB  - OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNPs) of
      rs2298771 and rs3812718 of the sodium channel alpha-subunit type 1 (SCN1A) gene
      affect the efficacy of carbamazepine (CBZ) treatment for seizures in Chinese Han
      epileptic patients. METHODS: SNP rs2298771 and rs3812718 of the SCN1A gene from
      628 patients were genotyped. CBZ monotherapy was administered to the subjects
      with new-onset partial seizures. The efficacy was defined as the decrease in the
      number of seizures. Four semi-quantitative levels were used to assess the
      efficacy: seizure-free (SF), >75% seizure decrease (SD), 50%-75% SD, and <50% SD
      in the number of seizures compared with patients' initial conditions. RESULTS:
      After the 12 month treatment with CBZ monotherapy, the rate of SF patients with G
      allele of the SNP rs2298771 was significantly lower than that in patients with
      the AA genotype (P=0.003). The heterozygote and homozygote of the G allele at SNP
      rs2298771 predicted the low SF rate (OR=2.101, 95% CI 1.289-3.425). Marginal
      significance was observed between the dichotomous efficacy of SF and non-SF in 3
      partial seizure types (P=0.028). CONCLUSION: rs2298771 is significantly
      associated with the efficacy of CBZ monotherapy in Chinese Han epileptic
      patients.

PMID- 24921388
TI  - Reliability of directional information in unsorted spikes and local field
      potentials recorded in human motor cortex.
AB  - OBJECTIVE: Action potentials and local field potentials (LFPs) recorded in
      primary motor cortex contain information about the direction of movement. LFPs
      are assumed to be more robust to signal instabilities than action potentials,
      which makes LFPs, along with action potentials, a promising signal source for
      brain-computer interface applications. Still, relatively little research has
      directly compared the utility of LFPs to action potentials in decoding movement
      direction in human motor cortex. APPROACH: We conducted intracortical multi
      electrode recordings in motor cortex of two persons (T2 and [S3]) as they
      performed a motor imagery task. We then compared the offline decoding performance
      of LFPs and spiking extracted from the same data recorded across a one-year
      period in each participant. MAIN RESULTS: We obtained offline prediction accuracy
      of movement direction and endpoint velocity in multiple LFP bands, with the best
      performance in the highest (200-400 Hz) LFP frequency band, presumably also
      containing low-pass filtered action potentials. Cross-frequency correlations of
      preferred directions and directional modulation index showed high similarity of
      directional information between action potential firing rates (spiking) and high
      frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands
      (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement
      more accurately than any individual LFP band, however combined decoding of all
      LFPs was statistically indistinguishable from spike-based performance. As the
      quality of spiking signals (i.e. signal amplitude) and the number of
      significantly modulated spiking units decreased, the offline decoding performance
      decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the
      number of significantly modulated LFP signals and their decoding accuracy
      followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]).
      SIGNIFICANCE: Field potentials provided comparable offline decoding performance
      to unsorted spikes. Thus, LFPs may provide useful external device control using
      current human intracortical recording technology. ( CLINICAL TRIAL REGISTRATION
      NUMBER: NCT00912041.).

PMID- 24921391
TI  - [Expression of Ephrin-B2 after focal cerebral ischemia in rats].
AB  - OBJECTIVE: To explore the expression profile of Ephrin-B2 in the ischemic
      penumbra after transient focal cerebral ischemia in rats, and to clarify the
      mechanism of Ephrin-B2 triggering angiogenesis. METHODS: Sprague-Dawley rats were
      randomly divided into a normal group, a sham operation group and ischemic
      reperfusion 1, 3, 7, 14, and 28 d groups. Suture-occluded method was used to
      establish the focal middle cerebral artery occlusion model and the ischemic brain
      was reperfused 2 h after the occlusion. Western blot and quantitative real-time
      reverse-transcription polymerase chain reaction were used to detect the dynamic
      expression profile of Ephrin-B2 in the penumbra cortex. Double immunofluorescence
      was used to speculate the location and the co-expression of Ephrin-B2 in blood
      vessels, neurons and astrocytes. Microvessel density was quantified by the number
      of CD31+ cells. Rats were subjected to neurologic functional tests by modified
      neurological severity scores (mNSS) before sacrifice. RESULTS: Compared with the
      sham group, Ephrin-B2 protein and mRNA level of the penumbra cortex in the
      ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 7
      and 14 (P<0.01), and declined at day 28. Double immunofluorescence indicated that
      Ehprin-b2 was expressed in the neurons, blood vessels and astrocytes; mNSS peaked
      at day 7, and gradually declined at day 14. The microvessel density of penumbra
      cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion,
      peaked at day 14 (P<0.01), and gradually declined at 48 h. CONCLUSION: Cerebral
      ischemia reperfusion induces the over-expression of Ephrin-B2, with a dynamic
      trend, suggesting that Ehprin-b2 may improve post-stroke functional recovery by
      enhancing angiogenesis and neurogenesis.

PMID- 24921392
TI  - [Immunological mechanism of class IV lupus nephritis through lymphocyte subsets
      and cytokine profile].
AB  - OBJECTIVE: To obtain a global view of lymphocyte subset changes in the peripheral
      blood and cytokine profile in patients with class IV lupus nephritis (LN).
      METHODS: A total of 30 patients with biopsy proven active class IV LN, 30
      patients with biopsy proven active class V LN, and 30 healthy controls were
      enrolled. Serum concentration of Th1 cytokines (IFN-gamma, IL-1, IL-2, and TNF
      alpha) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously
      analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte
      subsets was measured by flow cytometer. Clinical parameters such as urine protein
      of 24 h, autoantibodies and complement were detected. Pearson analysis was used
      to examine the relation between lymphocyte subsets and clinical parameters,
      cytokine and clinical parameters. RESULTS: The patients with class IV LN had
      evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There
      were no significant difference both in the ratio and number of CD4+ lymphocytes
      between the controls and the patients. In the patients with class IV LN, the
      ratio and number of CD4+ lymphocytes were both lower than those of the controls
      (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those
      of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+
      regulatory T cells (Tregs) was observed in the patients compared with healthy age
      matched controls (P<0.001). The abnormality of lymphocytes in class IV patients
      was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class
      IV patients, most of the detected cytokines levels were markedly elevated as
      compared with the controls, including Th2 cytokines INF-gamma (P<0.05), IL-2
      (P<0.05) and TNF-alpha (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05),
      IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly
      increased in class V patients. In addition to IL-2, all of them belonged to Th2
      (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between
      CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI
      (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive
      correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and
      creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01).
      There was also negative correlation between IL-10 and urine protein of 24 h (r=
      0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01),
      and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little
      correlation between cytokines and clinical parameters in patients with class V
      LN. CONCLUSION: There is extensive abnormality in lymphocyte subsets and cytokine
      profile in patients with class IV LN, which may be the mechanism of
      immunosuppressive agents to treat patients with class IV LN.

PMID- 24921393
TI  - [Effect of stress on myocardial apoptosis in ischemic preconditioning in rabbit
      hearts].
AB  - OBJECTIVE: To determine the influence of stress on myocardial apoptosis in
      ischemic preconditioning group (IPC). METHODS: Twenty-four Japanese white rabbits
      were randomly divided into 4 groups (n=6): an etomidate group (the Etom group) of
      depressed stress established by intravenous etomidate, an IPC group, an ischemic
      reperfusion group (the IR group) and a methylprednisolone group (the MP group).
      Myocardial apoptosis was examined by DNA-laddering, in situ nick-end labeling
      (TUNEL) and Hoechst dyeing. RESULTS: The DNA ladder increased in the Etom group.
      The percentage of apoptosis by TUNEL method was 1.7%+/-0.2% in the IPC group,
      2.3%+/-0.8% in the MP group, 3.8%+/-1.3% in the IR group and 3.0%+/-0.4% in the
      Etom group. Hoechst dying was 4.1%+/-0.9% in the IPC group, 3.5%+/-0.4% in the MP
      group, 6.2%+/-1.6% in the IR group and 7.6%+/-0.4% in the Etom group. There was
      significant difference between the IPC group and the Etom group or IR group, and
      also between the MP group and the IR group. CONCLUSION: A depressed stress
      response impairs the inhibition on myocardial apoptosis in ischemic
      preconditioning. Methylprednisolone may inhibit myocardial apoptosis.

PMID- 24921394
TI  - [Effect of miR-342-3p on chemotherapy sensitivity in triple-negative breast
      cancer].
AB  - OBJECTIVE: To study the effect of miR-342-3p on the chemotherapy sensitivity in
      triple-negative breast cancer (TNBC). METHODS: Tissue samples were collected from
      January 2011 to August 2013 samples in Jiangsu Cancer Hospital from a total of 32
      triple-negative breast cancer patients with preoperative chemotherapy, with 5
      cases of complete response (CR) and 27 cases of partial response (PR). We
      detected miR-342-3p expression of TNBC with RT-PCR. We transfected has-miR-342-3p
      mimic and inhibitor into breast cancer cell lines MDA-MB-231 by lipofection
      transfection and set up negative control mim-NC and inhi-NC. Group of mimic, mim
      NC, inhibitor and inhi-NC were cultivated with 2 MUmol /L paclitaxel, cisplatin
      or 4 MUmol/L doxorubicin for 48 h. The cell growth rates were measured by CCK8
      reagent kit, and the cell apoptosis rate by flow cytometry. RESULTS: The
      expressions of miRNA-342-3p in TNBC tissue of CR were higher than those of PR.
      The cell growth rates of mimic were lower and cell apoptosis rates were higher
      than those of min- NC after cultivating with paclitaxel or cisplatin for 48 h,
      with significant difference (P<0.05). The cell growth rates of inhibitor were
      higher and cell apoptosis rates lower than those of inhi-NC after cultivating
      with paclitaxel or cisplatin 48 h, with significant difference (P<0.05). The cell
      growth and cell apoptosis rates of mimic and inhibitor had no difference with
      those of mim-NC and inhi- NC after cultivating with doxorubicin 48 h (P>0.05).
      CONCLUSION: TNBC with high expression of miR-342-3p are more sensitive to
      chemotherapy. miRNA-342-3p may regulate the sensitivity of breast cancer cell
      line MDA-MB-231 to chemotherapy drugs paclitaxel and cisplatin, but can not
      affect the chemotherapy sensitivity of doxorubicin.

PMID- 24921395
TI  - [Construction of evaluation index system for equalization of basic public health
      services].
AB  - OBJECTIVE: To develop a scientific and effective evaluation index system for
      equalization of basic public health services. METHODS: Through 2 rounds of expert
      evaluation, based on the relative importance of expert scoring on each index,
      index was screened according to the scores of mean and coefficient of variation
      and the weight were determined. RESULTS: The two rounds of consulting experts
      response rates were more than 90%, and the average authority coefficients were
      0.779 and 0.781. The coordination coefficients were 0.229 and 0.349. The
      evaluation index system of basic public health services was composed of 3 first
      level, 17 second level and 47 third level indicators after 2 rounds of
      consultation. CONCLUSION: The evaluation index system of basic public health
      services is reasonable, and it can be used to evaluate the equalization of basic
      public health services.

PMID- 24921396
TI  - [Construction of competency model of 'excellent doctor' in Chinese medicine].
AB  - OBJECTIVE: To evaluate outstanding and ordinary persons from personal
      characteristics using competency as the important criteria, which is the future
      direction of medical education reform. METHODS: We carried on a behavior event
      interview about famous doctors of old traditional Chinese medicine, compiled
      competency dictionary, proceed control prediction test. SPSS and AMOS were used
      to be data analysis tools on statistics. We adopted the model of peer assessment
      and contrast to carry out empirical research. RESULTS: This project has carried
      on exploratory factor analysis and confirmatory factor analysis, established a
      "5A" competency model which include moral ability, thinking ability,
      communication ability, learning and practical ability. CONCLUSION: Competency
      model of "excellent doctor" in Chinese medicine has been validated, with good
      reliability and validity, and embodies the characteristics of traditional Chinese
      medicine personnel training, with theoretical and practical significance for
      excellence in medicine physician training.

PMID- 24921397
TI  - [Side population cells and progress in cancer stem cell research].
AB  - In recent years, cancer stem cells have become a hotspot for global researchers.
      Cancer stem cell theory deems that cells with self-renewal and differentiation
      potential play a key role in tumor resistance and relapse. These cells are named
      cancer stem cells. At present, the sorting methods include the side population
      cell sorting technique, screening techniques based on cell surface special
      markers, tumor sphere cultures, label retaining cell, ALDEFLUOR assays and so on.
      Side population cells are a small part of cells with the capacity of efflux DNA
      fluorescent dye Hoechst 33342 and present a low staining intensity in flow
      cytometry plot. Side population cells are rich in cancer stem cells, and its
      sorting method has been considered simple and effective in cancer stem cell
      research. 

PMID- 24921398
TI  - [Non-coding RNA and pancreatic cancer].
AB  - Non-coding RNA could regulate gene expression, involved in epigenetic
      modification, and participate in the cell differentiation, proliferation,
      apoptosis, and other life activities. Noncoding RNA also plays a crucial role in
      cancer occurrence, cancer cell invasion and distant metastases. Through mediating
      genome hyper-methylation, transcriptional regulation, regulation of transposable
      sequences, maintenance of genomic imprinting and DNA damage repair, noncoding RNA
      could regulate the growth and apoptosis of pancreatic cancer cells. Understanding
      the molecular mechanism of non-coding RNA in the development process of
      pancreatic cancer has important theoretical and practical value in the diagnosis,
      treatment and prognosis. 

PMID- 24921399
TI  - [Carotid intima-media thickness and estimated glomerular filtration rate in
      hypertensive patients].
AB  - OBJECTIVE: To determine the association between carotid atherosclerosis and renal
      function in hypertensive patients. METHODS: A total of 2 809 hypertensive
      patients aged (56.59+/-10.79) years were enrolled. Carotid intima-media thickness
      (cIMT) was derived via B-mode ultrasonography and chronic kidney disease (CKD)
      was evaluated by the estimated glomerular filtration rate (eGFR) with Cockcroft-
      Gault method. The patients were divided into 3 groups: a normal group, a thick
      group, and a plaque group according to the results of carotid ultrasonography.
      RESULTS: The eGFR of the normal group was (111.09+/-25.61) mL/(min.1.73m(2)),
      that of the thick group and the plaque group was (94.45+/-27.14)
      mL/(min.1.73m(2)) and (85.98+/-26.92) mL/ (min.1.73m(2)). Binary logistic
      analysis showed that age (OR=3.590), smoking status (OR=1.543), systolic blood
      pressure (OR=1.018), diastolic blood pressure (OR=0.977), fasting plasma glucose
      (OR=1.132), triglyceride (OR=0.873) and eGFR (OR=0.986) were significantly
      correlated with cIMT. Subgroup analyses on different genders showed that eGFR was
      a significant independent risk factor in men (OR=0.991) but not in women.
      CONCLUSION: The thicker the cIMT, the lower the eGFR in hypertensive patients.
      With the development of cIMT, eGFR gradually decreases and contributes to the
      occurrence and development of early-stage atherosclerosis in hypertensive
      patients.

PMID- 24921400
TI  - [Changes of miRNA after oral submucous fibrosis co-cultured with Salvia and low
      dose prednisolone].
AB  - OBJECTIVE: To explore and analyze the the expression change of miRNA associated
      with oral submucous fibrosis (OSF) treated by the Salvia combined with law-dose
      prednisolone. METHODS: Ten pairs of tissues from patients with typical early or
      advanced stage clinical pathological features of OSF and their paired normal
      tissues (internal control), were selected respectively. The miRNA expression
      profiles between the OSF and its paired controls were compared by the Affymetrix
      analysis. The primary normal oral mucous cells were cultured in arecoline (50
      MUg/mL) for 3, 6, 12 d (0 d ser ved as cont rol), and the primary OSF-fibroblast
      cells were cultured with Salvia (90 mg/mL) combined with low-dose prednisolone
      for 12, 24, 36 h (0 h served as control). The differential expression of miRNA
      was detected. RESULTS: Arecoline induced the expression changes of miRNAs in
      normal mucosal cells. Salvia combined with low doses of prednisolone reversed the
      related miRNA expression. CONCLUSION: MiRNAs play an essential role in the
      occurrence and development of OSF. Salvia combined with low-dose prednisolone can
      reverse the expression of related miRNAs in OSF cells.

PMID- 24921401
TI  - [Indwelling position and bacterial colonization of peripheral venous indwelling
      needles in patients with cardiovascular diseases].
AB  - OBJECTIVE: To study the characteristics of infections associated with peripheral
      venous indwelling needles and to explore the best indwelling position in patients
      with cardiovascular diseases from the perspective of bacteriology. METHODS: A
      total of 240 hospitalized patients from the Department of Cardiovascular
      Diseases, Xiangya Hospital, Central South University between November 2009 to
      July 2010 were randomly selected, and were divided into 3 groups according to the
      indwelling position and the indwelling time: a back of hand group (n=80), a
      forearm group (n=80) and a foot group (n=80). The above 3 groups were also
      divided into 4 subgroups according to the indwelling time (T1: 48 h <= t < 72 h;
      T2: 72 h <= t <= 96 h; T3: 96 h < t <= 120 h; and T4: 120 h < t <= 168 h) (20
      patients in each subgroup). The bacteria of samples from puncture position of the
      skin were respectively cultured and identified after skin disinfection, needle
      pulling out and sample puncture from the indwelling needle catheters,
      respectively. RESULTS: 1) After the skin disinfection, there was no bacterium in
      the skin samples of puncture position. 2) When the needles were pulled out, there
      was bacterial growth in the skin samples of puncture position in 41 patients in
      the 3 groups, and the bacterium was not detected in samples of the 3 groups at T1
      and T2 period. There was no significant difference in the positive rate of
      bacterial culture in the 3 groups at T3 and T4 period (P<0.05). 3) When the
      needles were pulled out. There was bacterial growth in the samples of indwelling
      needle catheters in 10 patients in the 3 groups; no bacterium was detected in the
      back of hand group and the forearm group at T1, T2, T3 and T4 period. In the foot
      group, there was no bacterium growth in the samples of indwelling needle
      catheters at T1 and T2 period, but there was bacterial growth in 4 patients at T3
      period and in 6 patients at T4 period. There was significant difference in the
      positive rate of bacterial culture in the samples of indwelling needle catheters
      in the 3 groups (P<0.05). CONCLUSION: The best indwelling position for peripheral
      venous indwelling needles is the forearm in patients with cardiovascular
      diseases.

PMID- 24921402
TI  - [Dichotic perception of Mandarin third tone by Mexican Chinese learners].
AB  - OBJECTIVE: To investigate the relationship between the advantage ear (cerebral
      hemisphere) of Spanish-speaking Mexican learners and the third Chinese tone.
      METHODS: Third tone Chinese vowel syllables were used as experimental materials
      with dichotic listening technology to test the Spanish-speaking Mexican Chinese
      learners (20-32 years old) who studied Chinese about 20 h. RESULTS: In terms of
      error rates to identify the third Chinese tone, the Spanish-speaking Mexican
      Chinese learners's reaction to the third tone suggested that their left ears were
      the advantageous ear (the right cerebral hemisphere) (Z=-2.091, P=0.036).
      CONCLUSION: The verbal information of tones influenced the perception of Mexican
      Chinese learners' mandarin tones. In the process of learning mandarin tones,
      Mexican Chinese learners gradually formed the category of tones.

PMID- 24921403
TI  - [Evaluation of the influence of humidity and temperature on the drug stability by
      initial average rate experiment].
AB  - OBJECTIVE: To evaluate the influence of temperature and humidity on the drug
      stability by initial average rate experiment, and to obtained the kinetic
      parameters. METHODS: The effect of concentration error, drug degradation extent,
      humidity and temperature numbers, humidity and temperature range, and average
      humidity and temperature on the accuracy and precision of kinetic parameters in
      the initial average rate experiment was explored. The stability of vitamin C, as
      a solid state model, was investigated by an initial average rate experiment.
      RESULTS: Under the same experimental conditions, the kinetic parameters obtained
      from this proposed method were comparable to those from classical isothermal
      experiment at constant humidity. The estimates were more accurate and precise by
      controlling the extent of drug degradation, changing humidity and temperature
      range, or by setting the average temperature closer to room temperature.
      CONCLUSION: Compared with isothermal experiments at constant humidity, our
      proposed method saves time, labor, and materials.

PMID- 24921404
TI  - Response to Oterino et al.: Analysis of endothelial precursor cells in chronic
      migraine: a case-control study.

PMID- 24921405
TI  - Problem areas in the International Classification of Headache Disorders, 3rd
      edition (beta).

PMID- 24921407
TI  - Changing practice and improving care using a low-risk tracheotomy clinical
      pathway.
AB  - IMPORTANCE: Tracheotomy is a common procedure. Postoperative care is usually
      managed by nonexpert clinicians. Prolonged decannulation is associated with a
      high incidence of complications. At present, no clinical protocol exists to guide
      clinicians through decannulation. To address this deficiency, we developed a low
      risk tracheotomy clinical pathway. OBJECTIVE: To determine the effect of our low
      risk tracheotomy clinical pathway on the time to decannulation and to determine
      its safety and sustainability by assessing the incidence of adverse events.
      DESIGN, SETTING, AND PARTICIPANTS: Our study combined retrospective and
      prospective cohorts from July 1, 2008, through January 31, 2012. Low-risk adult
      patients undergoing tracheotomy at a tertiary care hospital constituted the study
      population. A baseline cohort of 26 patients underwent retrospective assessment.
      After development of the pathway, a pilot group of 34 consecutive patients
      underwent evaluation; of these, 13 were ineligible because of high-risk factors,
      which included potential upper airway obstruction, unfavorable neck anatomy, or
      medical factors such as coagulopathy. To assess the sustainability of the
      pathway, a follow-up cohort underwent assessment. Of 107 consecutive patients, 39
      met the low-risk criteria. Length of follow-up was 30 days after decannulation.
      INTERVENTION: The low-risk tracheotomy clinical pathway, which provides a
      stepwise approach to decannulation. MAIN OUTCOMES AND MEASURES: Total time to
      decannulation (in days). We hypothesized that the pathway would reduce the total
      time to decannulation. The secondary outcome constituted adverse events. All
      hypotheses were formulated before data collection. RESULTS: Mean (SD) total time
      to decannulation in the baseline cohort was 15.50 (12.08) days. After
      implementation of the pathway in the pilot cohort, mean (SD) total time to
      decannulation decreased to 5.74 (2.79) days (P < .001). In the follow-up cohort,
      mean (SD) total time to decannulation was 8.13 (7.09) days (P = .003). We found
      no association between adverse events and use of the pathway. CONCLUSIONS AND
      RELEVANCE: Our low-risk tracheotomy clinical pathway is associated with a
      sustainable decrease in total time to decannulation without any associated
      increase in adverse events. We therefore believe that this pathway is a safe and
      effective tool to guide clinicians in the management of tracheotomy.

PMID- 24921406
TI  - Imprinted genes and the environment: links to the toxic metals arsenic, cadmium,
      lead and mercury.
AB  - Imprinted genes defy rules of Mendelian genetics with their expression tied to
      the parent from whom each allele was inherited. They are known to play a role in
      various diseases/disorders including fetal growth disruption, lower birth weight,
      obesity, and cancer. There is increasing interest in understanding their
      influence on environmentally-induced disease. The environment can be thought of
      broadly as including chemicals present in air, water and soil, as well as food.
      According to the Agency for Toxic Substances and Disease Registry (ATSDR), some
      of the highest ranking environmental chemicals of concern include
      metals/metalloids such as arsenic, cadmium, lead and mercury. The complex
      relationships between toxic metal exposure, imprinted gene regulation/expression
      and health outcomes are understudied. Herein we examine trends in imprinted gene
      biology, including an assessment of the imprinted genes and their known
      functional roles in the cell, particularly as they relate to toxic metals
      exposure and disease. The data highlight that many of the imprinted genes have
      known associations to developmental diseases and are enriched for their role in
      the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted
      genes resulted in the identification of an enrichment of binding sites for two
      transcription factor families, namely the zinc finger family II and PLAG
      transcription factors. Taken together these data contribute insight into the
      complex relationships between toxic metals in the environment and imprinted gene
      biology. 

PMID- 24921408
TI  - [The challenges of training in medical laboratories in Africa].
AB  - Sub-Saharan Africa has a considerable deficit in laboratory facilities. For a
      decade, international and national public and private initiatives have multiplied
      to expand both the supply and quality of medical laboratories in Africa. By 2020,
      the World Health Organization, with as its main operator the African Society for
      Laboratory Medicine, will have provided training for 30,000 laboratory personnel
      and encouraged 2,500 laboratories to begin the accreditation process. In
      addition, the World Health Organization recommendations for treatment and care of
      HIV-infected individuals in resource-limited settings, revised in 2013, emphasize
      the need for laboratory monitoring to guide antiretroviral therapy. The
      University Diploma in Biological Retrovirology at the Cheikh Anta Diop University
      in Dakar, Senegal, offers multidisciplinary training in French at the
      postgraduate level in the complex and diverse field of biological monitoring of
      HIV infection in Africa. In nearly 10 years, more than 200 African biologists
      have been trained. 

PMID- 24921410
TI  - Osteoarticular infections in young children: what has changed over the last
      years?
AB  - Osteoarticular infections remain a significant cause of morbidity worldwide in
      young children. They can have a devastating impact with a high rate of serious
      and long-lasting sequelae, especially on remaining growth. Depending on the
      localisation of infection, they manifest as osteomyelitis, septic arthritis, a
      combination of both (i.e., osteomyelitis with adjacent septic arthritis) or
      spondylodiscitis. Osteoarticular infections can be divided into three types
      according to the source of infection: haematogenous; secondary to contiguous
      infection; or secondary to direct inoculation. During the last few years, many
      principles regarding diagnostic assays and the microbiological causes of these
      infections have evolved in a significant manner. In the present current-opinion
      review, we discuss recent concepts regarding epidemiology, physiopathology, and
      the microbiology of bone and joint infections in young children, as well as
      clinical presentations, diagnosis, and treatment of these infections. Clinicians
      caring for children need to be especially well versed in these newer concepts as
      they can be used to guide evaluation and treatment. 

PMID- 24921411
TI  - The effect of red blood cell transfusion on intermittent hypoxemia in ELBW
      infants.
AB  - OBJECTIVE: To test the hypothesis that the effect of red blood cell (RBC)
      transfusion on intermittent hypoxemia (IH) in extremely low birth weight (ELBW)
      infants is dependent on postnatal age. STUDY DESIGN: Oxygen saturation of 130
      ELBW infants, who required transfusion, was monitored continuously for the first
      8 weeks of life. We compared the characteristics of IH (SpO2?80% for ?4 s and ?3
      min), 24 h before and both 24 h and 24 to 48 h after each RBC transfusion at
      three distinct time periods: Epoch 1, 1 to 7 days; Epoch 2, 8 to 28 days; and
      Epoch 3, >28 days. RESULT: In Epoch 1, the frequency and severity of IH events
      were not significantly different before and after transfusion. In both Epochs 2
      and 3 there was a decrease in IH frequency and severity 24 h after RBC
      transfusion that persisted for 48 h. In addition, there was a decrease in the
      overall time spent with SpO2 ?80% which persisted for 24 h after transfusion in
      Epochs 1 and 3, and for 48 h in Epoch 3. CONCLUSION: The benefit of RBC
      transfusion on IH is age dependent as improvement in the frequency and severity
      of IH after transfusion only occurs beyond the first week of life. These
      observations will aid clinician's decision making by clarifying the benefit of
      RBC transfusions on patterns of oxygenation in preterm infants.

PMID- 24921409
TI  - Viral oncolysis - can insights from measles be transferred to canine distemper
      virus?
AB  - Neoplastic diseases represent one of the most common causes of death among humans
      and animals. Currently available and applied therapeutic options often remain
      insufficient and unsatisfactory, therefore new and innovative strategies and
      approaches are highly needed. Periodically, oncolytic viruses have been in the
      center of interest since the first anecdotal description of their potential
      usefulness as an anti-tumor treatment concept. Though first reports referred to
      an incidental measles virus infection causing tumor regression in a patient
      suffering from lymphoma several decades ago, no final treatment concept has been
      developed since then. However, numerous viruses, such as herpes-, adeno- and
      paramyxoviruses, have been investigated, characterized, and modified with the aim
      to generate a new anti-cancer treatment option. Among the different viruses,
      measles virus still represents a highly interesting candidate for such an
      approach. Numerous different tumors of humans including malignant lymphoma, lung
      and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been
      studied in vitro and in vivo as potential targets. Moreover, several concepts
      using different virus preparations are now in clinical trials in humans and may
      proceed to a new treatment option. Surprisingly, only few studies have
      investigated viral oncolysis in veterinary medicine. The close relationship
      between measles virus (MV) and canine distemper virus (CDV), both are
      morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities
      to their human counterpart, indicates that both the virus and species dog
      represent a highly interesting translational model for future research in viral
      oncolysis. Several recent studies support such an assumption. It is therefore the
      aim of the present communication to outline the mechanisms of morbillivirus
      mediated oncolysis and to stimulate further research in this potentially
      expanding field of viral oncolysis in a highly suitable translational animal
      model for the benefit of humans and dogs. 

PMID- 24921412
TI  - Variation in treatment of neonatal abstinence syndrome in US children's
      hospitals, 2004-2011.
AB  - OBJECTIVE: Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome
      experienced by opioid-exposed infants. There is no standard treatment for NAS and
      surveys suggest wide variation in pharmacotherapy for NAS. Our objective was to
      determine whether different pharmacotherapies for NAS are associated with
      differences in outcomes and to determine whether pharmacotherapy and outcome vary
      by hospital. STUDY DESIGN: We used the Pediatric Health Information System
      Database from 2004 to 2011 to identify a cohort of infants with NAS requiring
      pharmacotherapy. Mixed effects hierarchical negative binomial models evaluated
      the association between pharmacotherapy and hospital with length of stay (LOS),
      length of treatment (LOT) and hospital charges, after adjusting for socioeconomic
      variables and comorbid clinical conditions. RESULT: Our cohort included 1424
      infants with NAS from 14 children's hospitals. Among hospitals in our sample, six
      used morphine, six used methadone and two used phenobarbital as primary initial
      treatment for NAS. In multivariate analysis, when compared with NAS patients
      initially treated with morphine, infants treated with methadone had shorter LOT
      (incidence rate ratio (IRR) = 0.55; P < 0.0001) and LOS (IRR = 0.60; P < 0.0001).
      Phenobarbital as a second-line agent was associated with increased LOT (IRR =
      2.09; P<0.0001), LOS (IRR = 1.78; P < 0.0001) and higher hospital charges (IRR =
      1.84; P < 0.0001). After controlling for case-mix, hospitals varied in LOT, LOS
      and hospital charges. CONCLUSION: We found variation in hospital in treatment for
      NAS among major US children's hospitals. In analyses controlling for possible
      confounders, methadone as initial treatment was associated with reduced LOT and
      hospital stay.

PMID- 24921413
TI  - Heart rate variability in encephalopathic newborns during and after therapeutic
      hypothermia.
AB  - OBJECTIVE: To evaluate whether heart rate variability (HRV) measures are
      predictive of neurological outcome in babies with hypoxic ischemic encephalopathy
      (HIE). STUDY DESIGN: This case-control investigation included 20 term
      encephalopathic newborns treated with systemic hypothermia in a regional neonatal
      intensive care unit. Electrocardiographic data were collected continuously during
      hypothermia. Spectral analysis of beat-to-beat heart rate interval was used to
      quantify HRV. HRV measures were compared between infants with adverse outcome
      (death or neurodevelopmental impairment at 15 months, n = 10) and those with
      favorable outcome (survivors without impairment, n = 10). RESULT: HRV
      differentiated infants by outcome during hypothermia through post-rewarming, with
      the best distinction between groups at 24 h and after 80 h of life. CONCLUSION:
      HRV during hypothermia treatment distinguished HIE babies who subsequently died
      or had neurodevelopmental impairment from intact survivors. This physiological
      biomarker may identify infants in need of adjuvant neuroprotective interventions.
      These findings warrant further investigation in a larger population of infants
      with HIE.

PMID- 24921414
TI  - Impact of PPARA and POR polymorphisms on tacrolimus pharmacokinetics and new
      onset diabetes in kidney transplant recipients.
AB  - Recent efforts have been made to identify genetic markers of CYP3A4 enzymatic
      activity within genes encoding for regulatory elements. The aim of the current
      study was to investigate the impact of polymorphism of PPARA and POR genes on
      tacrolimus (TAC) dose-adjusted trough concentration and risk of new-onset
      diabetes after transplantation (NODAT). A total of 241 White kidney transplant
      patients were genotyped for three functional single nucleotide polymorphisms:
      rs1057868 (*28) in POR, rs4253728:G>A, and rs4823613:A>G in PPARA. No significant
      genotype-dependent differences in TAC dose-adjusted trough concentration were
      observed for either POR or PPARA variants. No significant differences in the
      incidence of NODAT were observed between patients stratified by PPARA and POR
      genotypes. The frequency of NODAT among PPARA rs4253728 AA homozygotes (42%) was
      higher compared with heterozygotes (22%) and GG homozygotes (19%), but the
      difference was not significant. Testing TAC-medicated renal transplant recipients
      for POR and PPARA variants seems to have limited clinical application. 

PMID- 24921415
TI  - Tongue adhesion in the horned frog Ceratophrys sp.
AB  - Frogs are well-known to capture elusive prey with their protrusible and adhesive
      tongues. However, the adhesive performance of frog tongues and the mechanism of
      the contact formation with the prey item remain unknown. Here we measured for the
      first time adhesive forces and tongue contact areas in living individuals of a
      horned frog (Ceratophrys sp.) against glass. We found that Ceratophrys sp.
      generates adhesive forces well beyond its own body weight. Surprisingly, we found
      that the tongues adhered stronger in feeding trials in which the coverage of the
      tongue contact area with mucus was relatively low. Thus, besides the presence of
      mucus, other features of the frog tongue (surface profile, material properties)
      are important to generate sufficient adhesive forces. Overall, the experimental
      data shows that frog tongues can be best compared to pressure sensitive adhesives
      (PSAs) that are of common technical use as adhesive tapes or labels. 

PMID- 24921416
TI  - Adaptive approaches to licensing, health technology assessment, and introduction
      of drugs and devices.
AB  - BACKGROUND: Adaptive approaches to the introduction of drugs and medical devices
      involve the use of an evolving evidence base rather than conventional single
      point-in-time evaluations as a proposed means to promote patient access to
      innovation, reduce clinical uncertainty, ensure effectiveness, and improve the
      health technology development process. METHODS: This report summarizes a Health
      Technology Assessment International (HTAi) Policy Forum discussion, drawing on
      presentations from invited experts, discussions among attendees about real-world
      case examples, and background paper. RESULTS: For adaptive approaches to be
      understood, accepted, and implemented, the Forum identified several key issues
      that must be addressed. These include the need to define the goals of and to set
      priorities for adaptive approaches; to examine evidence collection approaches; to
      clarify the roles and responsibilities of stakeholders; to understand the
      implications of adaptive approaches on current legal and ethical standards; to
      determine costs of such approaches and how they will be met; and to identify
      differences in applying adaptive approaches to drugs versus medical devices. The
      Forum also explored the different implications of adaptive approaches for various
      stakeholders, including patients, regulators, HTA/coverage bodies, health
      systems, clinicians, and industry. CONCLUSIONS: A key outcome of the meeting was
      a clearer understanding of the opportunities and challenges adaptive approaches
      present. Furthermore, the Forum brought to light the critical importance of
      recognizing and including a full range of stakeholders as contributors to a
      shared decision-making model implicit in adaptive pathways in future discussions
      on, and implementation of, adaptive approaches.

PMID- 24921417
TI  - Prospective evaluation of new 22 gauge endoscopic ultrasound core needle using
      capillary sampling with stylet slow-pull technique for intra-abdominal solid
      masses.
AB  - GOALS: The aim of this study was to evaluate the adequacy and diagnostic yield of
      the histologic core obtained with a 22 G endoscopic ultrasound histology needle
      using capillary sampling with stylet slow-pull technique without on-site
      cytopathologist. BACKGROUND: No standard technique for new EUS histology needle
      has been established. STUDY: A total of 125 consecutive patients with intra
      abdominal solid masses were enrolled prospectively between October 2011 and March
      2013. EUS-guided fine needle biopsy (EUS-FNB) with a 22 G histology needle using
      capillary sampling with stylet slow-pull technique was performed. RESULTS: A
      total of 133 EUS-FNB procedures targeting the pancreas, lymph node,
      retroperitoneal mass, ampulla of Vater, gallbladder, common bile duct, duodenum,
      and liver were performed in 125 patients. EUS-FNB was technically feasible in all
      cases, and a visible core was obtained in 128 cases (96%). Histologic core
      specimens suitable for pathologic assessment were reported in 111 cases (83%).
      There were no procedure-related adverse events. According to the determinants of
      malignancy with EUS-FNB, the sensitivity, specificity, positive and negative
      predictive values, and accuracy were 85%, 98%, 99%, 77%, and 89%, respectively.
      In addition, histologic architecture with or without immunohistochemical staining
      of the core biopsy specimens was useful for pathologic confirmation in 101 cases
      (76%). CONCLUSIONS: A 22 G EUS-FNB using capillary sampling with stylet slow-pull
      technique showed a high diagnostic yield and histologic core acquisition for the
      histologic diagnosis of various intra-abdominal masses without an on-site
      cytopathologist. Furthermore, a histologic core with or without
      immunohistochemical staining was helpful for clinical decision making in 76% of
      the intra-abdominal solid masses.

PMID- 24921418
TI  - Depression stigma and treatment preferences among Orthodox and non-Orthodox Jews.
AB  - Anecdotal reports of increased stigma toward mental illness among Orthodox Jews
      seems to conflict with an existing literature describing less stigmatization
      toward depression among Jewish individuals. This online survey study investigated
      stigma toward depression and treatment preference among Orthodox and non-Orthodox
      Jews (N = 391). All participants were presented with a depression vignette to
      assess for stigma and then randomized to a vignette depicting a treatment
      modality (behaviorally oriented or insight oriented) to assess for treatment
      preference across several delivery options (individual, group, or Internet).
      Results indicated elevated depression stigma among Orthodox Jews as expressed by
      elevated levels of secrecy, treatment-seeking stigma, family/marriage stigma, and
      stigmatizing experiences, but not attitudinal social distancing. No group
      differences were found with respect to overall treatment preference, treatment
      modality, or manner of delivery. Overall, participants preferred individual
      therapy more than group and Internet therapy and preferred group therapy more
      than Internet therapy. Clinical and research implications are discussed. 

PMID- 24921419
TI  - Similarities and differences in borderline personality disorder and schizophrenia
      with voice hearing.
AB  - The aim of the study was to identify psychopathological similarities and
      differences in borderline personality disorder (BPD) and schizophrenia. We
      compared 23 female patients with a BPD and 21 female patients with schizophrenia
      according to auditory verbal hallucinations (AVHs), dissociation, childhood
      trauma, and additional psychotic symptoms. The character of AVH was similar with
      regard to commenting voices, location, and foreign voices. Major differences were
      found in the prevalence of negative symptoms, bizarre delusions, and formal
      thought disorder. These characteristics were more frequent in schizophrenia and
      negatively correlated with childhood traumatization. A history of childhood
      traumatization and dissociative symptoms was significantly more frequent in BPD.
      AVHs in BPD and schizophrenia are not distinguishable in terms of the
      historically grown criteria in Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision for diagnosing schizophrenia. Other
      symptoms such as delusions, negative symptoms, formal thought disorder, and
      dissociative psychopathology could help to differentiate between both groups. 

PMID- 24921420
TI  - Patients' perspectives on residual symptoms in bipolar disorder: a focus group
      study.
AB  - Euthymic bipolar patients are often impacted by residual symptoms (RSs) that
      increase the risk of relapse or low functioning. We aimed to identify the
      perceptions of RSs, barriers to management, and service needs in euthymic bipolar
      patients. A qualitative methodology (focus group) was used. The interviews were
      investigated using a semistructured guide, tape-recorded, transcribed verbatim,
      and analyzed thematically. Twenty-three bipolar patients expressed concern about
      several RSs, such as emotional dysregulation, circadian rhythm disruption,
      cognitive impairment, low self-esteem, and physical symptoms. They reported
      concern about the impact of RSs on their functioning and about the need for more
      systematic assessment of RSs during interepisode visits. Selection bias may have
      occurred because the recruitment was limited to France and there may be cultural
      differences in the perceptions of RSs. Bipolar patients experienced bipolar
      disorder as a chronic disorder because they frequently continued to suffer from
      RSs associated with a functional impact. 

PMID- 24921421
TI  - Complicated grief and depression in young adults: personality and relationship
      quality.
AB  - Young adults experience problematic responses to loss more often than is commonly
      recognized. Few empirical studies have examined the contribution of intrapersonal
      and interpersonal characteristics to grief and depression in bereaved young
      adults. This study investigated the association of dependency and quality of the
      relationship with the deceased (i.e., depth and conflict) with complicated grief
      (CG) and depression. Participants were 157 young adults aged 17 to 29 years who
      experienced loss of a family member or close friend within the past 3 years (mean
      = 1.74 years). Participants completed the Inventory of Complicated Grief, Beck
      Depression Inventory, Depth and Conflict subscales of the Quality of
      Relationships Inventory, and the Dependency subscale of the Depressive
      Experiences Questionnaire. Relationships among dependency and interpersonal depth
      and conflict and CG and depression were examined through analyses of covariance.
      Sixteen percent of participants met criteria for CG and 34% had mild to severe
      depression. Dependency and depth were independently related to CG and dependency
      was related to depression, but the pattern of associations was somewhat different
      for each outcome. Greater depth was associated with CG, at both high and low
      levels of dependency. High levels of dependency were related to more depressive
      symptoms. Interpretation of the findings is limited by the relatively small
      sample size and cross-sectional design. CG and depression are related but
      distinct responses to loss. Although dependency is associated with both CG and
      depression after loss, relationships between the bereaved and deceased that are
      characterized by high levels of depth are particularly related to the development
      of CG symptoms. 

PMID- 24921422
TI  - CE: Diabetes and puberty: a glycemic challenge.
AB  - OVERVIEW: As children with diabetes enter adolescence, the physical and
      psychological changes of puberty add to the challenges of disease management.
      This often leads to increased stress for both parent and child and to poor
      overall glucose control with potential short- and long-term complications. During
      this period of transition, nurses play a central role in teaching patients and
      their families about the effects of puberty on insulin sensitivity and glucose
      metabolism, and in discussing how the emotional and behavioral changes associated
      with this challenging time can affect diabetes management.

PMID- 24921423
TI  - CE: Original research: the perceptions of health care team members about engaging
      patients in care redesign.
AB  - OBJECTIVE: This study sought to explore the perceptions of health care workers
      about engaging patients as partners on care redesign teams under a program called
      Transforming Care at the Bedside (TCAB), and to examine the facilitating factors,
      barriers, and effects of such engagement. DESIGN: This descriptive, qualitative
      study collected data through focus groups and individual interviews. Participants
      included health care providers and managers from five units at three hospitals in
      a university-affiliated health care center in Canada. METHODS: A total of nine
      focus groups and 13 individual interviews were conducted in April 2012, 18 months
      after the TCAB program began in September 2010. Content analysis was used to
      analyze the qualitative data. FINDINGS: Health care providers and managers
      benefited from engaging patients in the decision-making process because the
      patients brought a new point of view. Involving the patients exposed team members
      to valuable information that they hadn't previously thought about during decision
      making. CONCLUSION: Health care teams stand to benefit from engaging patients in
      the change process. Patients contribute a different point of view, and this helps
      to ensure that the changes proposed and implemented address their needs.

PMID- 24921424
TI  - Infection prevention issues in long-term care.
AB  - PURPOSE OF REVIEW: Infections and antimicrobial use are common in residents of
      long-term care facilities. This review discusses recent articles that address
      infection prevention and control and antimicrobial stewardship in these
      facilities. RECENT FINDINGS: National surveys confirm the continuing high
      prevalence of infections in residents of long-term care facilities, with the
      greatest risk for patients with the highest acuity and greatest functional
      disability. Long-term acute care facilities are a unique environment where
      residents are characterized by high levels of indwelling device use and
      antimicrobial-resistant organisms. The major determinant of antimicrobial
      resistance in long-term care facilities is antimicrobial use. The Centers for
      Disease Control (CDC) has proposed revised evidence-based definitions for
      surveillance of infections on the basis of the original McGeer criteria.
      Consensus national performance standards for infection prevention and
      antimicrobial stewardship programs in long-term care facilities have been
      developed in a European initiative. Evidence to support the efficacy of infection
      control programs is limited. Antimicrobial stewardship programs may, however, be
      effective in reducing inappropriate antimicrobial use. SUMMARY: The extent to
      which endemic infections or antimicrobial resistance in long-term care facilities
      can be prevented remains unclear. Efforts to limit infections in these facilities
      should focus on outbreak prevention and standard procedures for environmental
      cleaning, food preparation, and hand hygiene, together with optimal resident
      medical care. Antimicrobial stewardship programs should be implemented.

PMID- 24921425
TI  - How costs change with infection prevention efforts.
AB  - PURPOSE OF REVIEW: To describe articles since January 2013 that include
      information on how costs change with infection prevention efforts. RECENT
      FINDINGS: Three articles described only the costs imposed by nosocomial infection
      and so provided limited information about whether or not infection prevention
      efforts should be changed. One article was found that described the costs of
      supplying alcohol-based hand run in low-income countries. Eight articles showed
      the extra costs and cost savings from changing infection prevention programmes
      and discussed the health benefits. All concluded that the changes are
      economically worthwhile. There was a systematic review of the costs of
      methicillin-resistant Staphylococcus aureus control programmes and a methods
      article for how to make cost estimates for infection prevention programmes.
      SUMMARY: The balance has shifted away from studies that report the high cost of
      nosocomial infections toward articles that address the value for money of
      infection prevention. This is good as simply showing a disease is high cost does
      not inform decisions to reduce it. More research, done well, on the costs of
      implementation, cost savings and change to health benefits in this area needs to
      be done as many gaps exist in our knowledge.

PMID- 24921426
TI  - Update on infection control challenges in special pediatric populations.
AB  - PURPOSE OF REVIEW: Compared with adults, neonatal and pediatric populations are
      especially vulnerable patients who have specific diagnostic and therapeutic
      differences; therefore, the standard infection control practices designed for
      adults are sometimes not effective or need modifications to work. This review
      focuses on the recent literature addressing the challenges and successes in
      preventing healthcare-associated infections (HAIs) in children. RECENT FINDINGS:
      Improving the implementation of pediatric versions of preventive bundles focusing
      on proper catheter insertion and maintenance, mainly as a part of a larger
      multimodal strategy, is effective in reducing the central-line-associated
      bloodstream infections in neonatal and pediatric populations including oncology
      patients. Appropriate feeding, antimicrobial stewardship, and infection control
      measures should be combined in reducing necrotizing enterocolitis in preterm
      neonates. Implementing a multimodal bundle strategy adapted for pediatric
      population is successful in preventing ventilator-associated pneumonia.
      Appropriate use of antimicrobial prophylaxis remains the cornerstone for
      preventing surgical-site infections irrespective of age, with few additional
      effective adjuvant preventive practices in specific pediatric patients. SUMMARY:
      Several evidence-based practices are effective in reducing the incidence and the
      impact of HAIs in children; however, proper implementation remains a challenge.
      Additionally, several adult preventive practices are still unestablished in
      children and need further thorough examination.

PMID- 24921427
TI  - Individual differences in emotion lateralisation and the processing of emotional
      information arising from social interactions.
AB  - Previous research examining the possible association between emotion
      lateralisation and social anxiety has found conflicting results. In this paper
      two studies are presented to assess two aspects related to different features of
      social anxiety: fear of negative evaluation (FNE) and emotion regulation.
      Lateralisation for the processing of facial emotion was measured using the
      chimeric faces test. Individuals with greater FNE were more strongly lateralised
      to the right hemisphere for the processing of anger, happiness and sadness; and,
      for the processing of fearful faces the relationship was found for females only.
      Emotion regulation strategies were reduced to two factors: positive strategies
      and negative strategies. For males, but not females, greater reported use of
      negative emotion strategies is associated with stronger right hemisphere
      lateralisation for processing negative emotions. The implications for further
      understanding the neuropsychological processing of emotion in individuals with
      social anxiety are discussed. 

PMID- 24921428
TI  - Disequilibrium of M1 and M2 macrophages correlates with the development of
      experimental inflammatory bowel diseases.
AB  - Ulcerative colitis, a major inflammatory bowel disease, is an idiopathic
      inflammatory disorder of the colonic mucosa, accompanied by an aberrant immune
      reaction to intestinal microflora. Macrophages are central mediators of
      intestinal immune homeostasis and inflammation. The relationship between
      macrophages and the pathogenesis of colitis is poorly understood. We aimed to
      characterize the changing populations and roles of M1/M2 macrophages in colitis.
      We demonstrated that M1 macrophages increased and M2 macrophages decreased in
      colitis, accompanied by Interleukin (IL)-23 and Tumor necrosis factor-alpha
      induction and IL-10 suppression. Transfer of M2 macrophages reduced dextran
      sodium sulfate-induced colitis by inducing IL-10 production and promoting
      regulatory T-cell generation. In vivo neutralization of IL-10 partially reduced
      the effects of M2 transfer. These findings suggest that macrophages play a
      critical role in colitis; specifically, disequilibrium of macrophage subsets
      promotes colitis development. A shift from the M1 to M2 phenotype reduces colitis
      by inducing IL-10; thus, mobilization of M2 macrophages could be a novel approach
      to colitis therapy. 

PMID- 24921429
TI  - Spinal metastases due to thyroid carcinoma: an analysis of 202 patients.
AB  - BACKGROUND: Spinal metastases (SMs) due to thyroid cancer (TC) are associated
      with significantly reduced quality of life. The goal of this study is to analyze
      the clinical manifestations, presentation, and treatments of TC SMs, and to
      describe specific features of SMs associated with different TC types. PATIENTS
      AND METHODS: A retrospective analysis of 202 TC SM patients treated at Medstar
      Washington Hospital Center (37) and collected from the literature (165) was
      performed. RESULTS: The mean age of patients with SMs was 56.9+/-14.7 years, and
      the female-to-male ratio was 2.1:1. Of all patients, 29% (28% of follicular
      thyroid cancer [FTC] and 37% of papillary thyroid cancer [PTC]) had SMs only.
      Twenty-nine percent of all patients and 54% of patients with single-site SMs had
      neither bone non-SMs nor solid organ metastases at the time of presentation.
      Thirty-five percent of patients had SMs as an initial presentation of TC. TC
      patients presenting with SMs had a lower rate of other bone and visceral
      involvement compared with patients whose SMs were diagnosed at the time of
      thyroid surgery or during follow-up (p<0.05). SMs were more often the initial
      manifestation of FTC (41% vs. 24%), while PTC SMs were more commonly diagnosed
      after TC diagnosis (76% vs. 59%; p<0.05). PTC SMs were more frequently diagnosed
      as synchronous (63% vs. 36% in FTC) versus FTC SMs that developed as metachronous
      metastases (64% vs. 37% in PTC; p<0.01). All FTC SMs developed within 82 (0-372)
      months and all PTC SMs within 35 (0-144) months (p<0.01). In FTC SMs as TC
      manifestation, solid organ metastases involvement was less common than in FTC SMs
      that were found after TC diagnosis (34% vs. 67%; p<0.01); multisite FTC SMs
      compared to solitary FTC SMs were associated with the development of other bone
      nonspinal metastases (82% vs. 30%; p<0.01) and solitary organ metastases (65% vs.
      41%; p<0.01). These correlations were not observed in PTC SMs. FTC patients often
      had neural structure compression (myelopathy/radiculopathy; 72% vs. 36% in PTC),
      while PTC patients frequently were asymptomatic (38% vs. 5% in FTC; p<0.01). FTC
      SMs more commonly were (131)I-avid (p<0.01). FTC patients required surgery more
      frequently (72% vs. 55% in PTC; p<0.05). CONCLUSIONS: Our study reveals that a
      significant part of TC SMs patients have solitary spinal involvement at the time
      of presentation and may be considered for aggressive treatment with the intention
      to improve quality of life and survival. FTC SMs and PTC SMs appear to have
      distinct presentations, behavior, and treatment modalities, and should be
      categorized separately for treatment and follow-up planning.

PMID- 24921431
TI  - kgp, rgpA, and rgpB DNA vaccines induce antibody responses in experimental peri
      implantitis.
AB  - BACKGROUND: Peri-implantitis is the key factor for implant failure. This study
      aims to evaluate kgp, rgpA, and rgpB DNA vaccines to induce an immune response
      and prevent peri-implantitis. METHODS: The kgp, rgpA, and rgpB genes were
      amplified by polymerase chain reaction (PCR) from Porphyromonas gingivalis (Pg)
      ATCC 33277 and cloned into the pVAX1 vector. Titanium implants were placed into
      the mandibular bone of dogs. Three months later, the animals were divided into
      four groups, immunized with pVAX1-kgp, pVAX1-rgpA, pVAX1-rgpB, or pVAX1. Cotton
      ligatures infiltrated with Pg were tied around the neck of the implants.
      Immunoglobulin (Ig)G and IgA antibodies were detected by enzyme-linked
      immunosorbent assay before and after immunization. RESULTS: The kgp, rgpA, and
      rgpB genes were successfully cloned into the pVAX1 plasmid. Animals immunized
      with pVAX1-kgp and pVAX1-rgpA showed higher titers of IgG and IgA antibodies
      compared to those before immunization (P <0.05) and compared to those that were
      immunized with pVAX1 and pVAX1-rgpB, whereas there were no significant
      differences in the animals treated with pVAX1 and pVAX1-rgpB. Furthermore, among
      these, the kgp DNA vaccine was more effective. The bone losses of the groups with
      pVAX1-kgp and pVAX1-rgpA were significantly attenuated. CONCLUSION: pVAX1-kgp and
      pVAX1-rgpA DNA vaccines enhanced immunity responses and significantly retarded
      bone loss in experimental peri-implantitis animal models, whereas pVAX1-rgpB was
      ineffective.

PMID- 24921433
TI  - Delirium in advanced cancer: screening for the incidence on admission to an
      inpatient hospice unit.
AB  - BACKGROUND: Delirium is a common underdiagnosed condition in advanced cancer
      leading to increased distress, morbidity, and mortality. Screening improves
      detection but there is no consensus as to the best screening tool to use with
      patients with advanced cancer. OBJECTIVE: To determine the incidence of delirium
      in patients with advanced cancer within 72 hours of admission to an acute
      inpatient hospice using clinical judgement and validated screening tools. METHOD:
      One hundred consecutive patients with advanced cancer were invited to be screened
      for delirium within 72 hours of admission to an acute inpatient hospice unit. Two
      validated tools were used, the Delirium Rating Scale-Revised 98 (DRS-R-98) and
      the Confusion Assessment METHOD (CAM) shortened diagnostic algorithm. These
      results were compared with clinical assessment by review of medical charts.
      RESULTS: Of 100 consecutive admissions 51 participated and of these 22 (43.1%)
      screened positive for delirium with CAM and/or DRS-R-98 compared to 15 (29.4%) by
      clinical assessment. Eleven (21.6%) were identified as hypoactive delirium and 5
      (9.8%) as subsyndromal delirium. CONCLUSION: This study confirms that delirium is
      a common condition in patients with advanced cancer. While there remains a lack
      of consensus regarding the choice of delirium screening tool this study supports
      the CAM as being appropriate. Further research may determine the optimal
      screening tool for delirium enabling the development of best practice clinical
      guidelines for routine medical practice.

PMID- 24921432
TI  - Porphyromonas gingivalis lipopolysaccharide upregulates insulin secretion from
      pancreatic beta cell line MIN6.
AB  - BACKGROUND: A close association between periodontitis and diabetes has been
      demonstrated in human cross-sectional studies, but an exact relationship between
      periodontitis and prediabetes has not been established. Previous studies using
      animal model systems consistently have shown that hyperinsulinemia occurs in
      animals with periodontitis compared to animals with healthy periodontium (while
      maintaining normoglycemia). Because bacterial lipopolysaccharide (LPS) plays an
      important role in the pathogenesis of periodontitis, we hypothesized that LPS may
      stimulate insulin secretion through a direct effect on beta cell function. To
      test this hypothesis, pancreatic beta cell line MIN6 cells were used to determine
      the effect of Porphyromonas gingivalis (Pg) LPS on insulin secretion.
      Furthermore, expression of genes altered by Pg LPS in innate immunity and insulin
      signaling pathways was determined. METHODS: MIN6 cells were grown in medium with
      glucose concentration of normoglycemia (5.5 mM). Pg LPS was added to each well at
      final concentrations of 50, 200, and 500 ng/mL. Insulin secretion was measured
      using enzyme-linked immunosorbent assay. Gene expression levels altered by Pg LPS
      were determined by polymerase chain reaction (PCR) array for mouse innate and
      adaptive immunity response and mouse insulin-signaling pathways, and results were
      confirmed for specific genes of interest by quantitative PCR. RESULTS: Pg LPS
      stimulated insulin secretion in the normoglycemic condition by ~1.5- to 3.0-fold
      depending on the concentration of LPS. Pg LPS treatment altered the expression of
      several genes involved in innate and adaptive immune response and insulin
      signaling pathway. Pg LPS upregulated the expression of the immune response
      related genes cluster of differentiation 8a (Cd8a), Cd14, and intercellular
      adhesion molecule-1 (Icam1) by about two-fold. LPS also increased the expression
      of two insulin signaling-related genes, glucose-6-phosphatase catalytic subunit
      (G6pc) and insulin-like 3 (Insl3), by three- to four-fold. CONCLUSIONS: We have
      demonstrated for the first time that Pg LPS stimulates insulin secretion by
      pancreatic beta cell line MIN cells. Pg LPS may have significant implications on
      the development of beta cell compensation and insulin resistance in prediabetes
      in individuals with periodontitis.

PMID- 24921434
TI  - NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed
      combination of beclometasone and formoterol to treat large and small airways in
      asthma.
AB  - INTRODUCTION: Airway inflammation and remodelling in asthma occur in the large
      airways and also in the small airways. The small airways are those < 2 mm in
      diameter and are significant sites of chronic asthmatic inflammation. It is
      important, therefore, to target the small as well as the large airways in any
      strategy for effective treatment of this disease. AREAS COVERED: The present
      review deals with the recently developed fixed dose drug combination of
      beclometasone dipropionate/formoterol fumarate that emits extrafine particles
      when delivered from an innovative dry powder inhaler (DPI), NEXThaler(r). The aim
      is to present the technical and clinical aspects of aerosolized drug delivery to
      the lungs. EXPERT OPINION: The data show that the NEXThaler DPI is an efficient
      device for the management of persistent asthma. The evaluation of the inhalation
      profiles through the NEXThaler DPI demonstrates that device activation and
      consistent dose delivery occurs at patient achievable inhalation flow rates, and
      supports the broad utility of the NEXThaler DPI in patients with asthma. Overall,
      all the effectiveness, efficiency and satisfaction outcomes demonstrate the
      NEXThaler DPI is easy to use.

PMID- 24921435
TI  - Respiratory syncytial virus: should we be concerned in pregnancy?

PMID- 24921436
TI  - Twenty years and counting: taking the lessons learned from ICPD to move the
      sexual and reproductive health and rights agenda forward.
AB  - The women's rights movement and the sexual and reproductive health and rights
      (SRHR) movement have been actively involved in ensuring that the gains (on sexual
      and reproductive health, reproductive rights and women's sexuality) made during
      the 1994 International Conference on Population and Development (ICPD) in Cairo
      and the 1995 fourth World Conference on Women in Beijing are maintained and
      captured in the new development framework. International processes, especially
      the United Nations Population Fund's ICPD Beyond 2014 work, have proven essential
      platforms for this. However, the current geopolitical scenario provides a
      challenging environment to ensure that the comprehensive Cairo+20 agenda is given
      the due attention and place it deserves and requires. This article aims to
      articulate the critical gaps in political discourse and commitment to the ICPD
      agenda from 1994 to the time of ICPD beyond 2014. Governments' potential lack of
      commitment to crucial issues of SRHR is also examined and discussed in the first
      section. In the second section, the article looks at progress and gaps regarding
      specific and commonly used measures of SRHR as an indicator of where discourse
      and commitment are required. In the third section, as a follow-up to the previous
      one, the article discusses the need to and the possibilities of articulating and
      positioning the rights discourse more clearly within the current complex global
      discourse as a necessary step in the movement's political discourse. In the last
      section, some key challenges and opportunities, as well as identified
      recommendations, are discussed with regard to the way ahead for the SRHR agenda
      in the 2014 and beyond. 

PMID- 24921437
TI  - Reduced graphene oxide modified highly ordered TiO2 nanotube arrays
      photoelectrode with enhanced photoelectrocatalytic performance under visible
      light irradiation.
AB  - In this paper, reduced graphene oxide modified highly ordered TiO2 nanotube
      arrays (RGO-TNTs) have been fabricated and used for photoelectrocatalytic (PEC)
      degradation of organic pollutants under visible light irradiation. Firstly, the
      RGO-TNT electrode was characterized by scanning electron microscopy (SEM), X-ray
      diffraction (XRD), Raman, FT-IR, X-ray photoelectron spectroscopy (XPS) and UV
      vis diffuse reflectance spectroscopy. The responsive photocurrent and
      electrochemical impedance spectroscopy (EIS) results indicated that our present
      RGO-TNTs displayed superior photoresponsive and electron transfer performances
      compared with bare TNTs. Moreover, by comparison with bare TNT electrode, the RGO
      TNT arrays showed stable and evidently improved PEC activity for degradation of
      methyl orange (MO) under visible light illumination. This might be attributed to
      the introduction of RGO, which extended the absorption edge and promoted electron
      hole separation in the PEC process. Furthermore, owing to the synergetic effect
      of photocatalysis and electrocatalysis in the PEC process, the efficiency of PEC
      process (3.0 * 10(-3) min(-1)) is ca. 7.9 and 2.5 times faster than that of the
      electrochemical process (3.8 * 10(-4) min(-1)) and photocatalytic process (1.2 *
      10(-3) min(-1)), respectively. Our investigation likely provides new
      opportunities for developing stable and efficient one-dimensional graphene
      modified TNT-based catalysts for PEC degradation of organic pollutants under
      visible light illumination. 

PMID- 24921438
TI  - Manipulating the charge transfer at CuPc/graphene interface by O2 plasma
      treatments.
AB  - The manipulation of charge transfer at CuPc/graphene interface has been
      demonstrated by treating pristine graphene with O2 plasma. As revealed by in situ
      ultraviolet photoelectron spectroscopy measurements, a much stronger interfacial
      charge transfer occurs when the pristine graphene is exposed to O2 plasma prior
      to the growth of CuPc films, which is attributed to the increased work function
      of graphene after O2 plasma treatment. Moreover, the highest occupied molecular
      orbital leading edge of CuPc locates at ~0.80 eV below substrate Fermi level on
      O2 plasma treated graphene, whereas it locates at ~1.10 eV on pristine graphene.
      Our findings provide detailed information regarding the electronic structure at
      CuPc/graphene and CuPc/O2 plasma treated graphene interfaces. The increased work
      function in combination with the relatively smaller energy offset between the
      highest occupied molecular orbital of CuPc and Fermi level of O2 plasma treated
      graphene facilitates the extraction of holes at the interface, and hence paves
      the way for improving the performance of graphene-based organic photovoltaic
      cells.

PMID- 24921440
TI  - Editorial.

PMID- 24921441
TI  - Guest editorial.

PMID- 24921439
TI  - Acute psychological and physical stress transiently enhances brachial artery flow
      mediated dilation stimulated by exercise-induced increases in shear stress.
AB  - Exercise elevates conduit artery shear stress and stimulates flow-mediated
      dilation (FMD). However, little is known regarding the impact of acute
      psychological and physical stress on this response. The purpose of this study was
      to examine the impact of the Trier Social Stress Test (TSST (speech and
      arithmetic tasks)) and a cold pressor test (CPT) with and without social
      evaluation (SE) on exercise-induced brachial artery FMD (EX-FMD). A total of 59
      healthy male subjects were randomly assigned to 1 of 3 conditions: TSST, CPT, or
      CPT with SE. During 6 min of handgrip exercise, brachial artery EX-FMD was
      assessed before and 15 and 35 min poststress with echo and Doppler ultrasound.
      Shear stress was estimated as shear rate, calculated as brachial artery mean
      blood velocity/brachial artery diameter. Results are means +/- SD. All conditions
      elicited significant physiological stress responses. Salivary cortisol increased
      from 4.6 +/- 2.4 nmol/L to 10.0 +/- 5.0 nmol/L (p < 0.001; condition effect: p =
      0.292). Mean arterial pressure increased from 98.6 +/- 12.1 mm Hg to 131.9 +/-
      18.7 mm Hg (p < 0.001; condition effect: p = 0.664). Exercise shear rate did not
      differ between conditions (p = 0.592), although it was modestly lower poststress
      (prestress: 72.3 +/- 4.5 s(-1); 15 min poststress: 70.8 +/- 5.4 s(-1); 35 min
      poststress: 70.6 +/- 6.1 s(-1); trial effect: p = 0.011). EX-FMD increased from
      prestress to 15 min poststress in all conditions (prestress: 6.2% +/- 2.8%; 15
      min poststress: 7.9% +/- 3.2%; 35 min poststress: 6.6% +/- 2.9%; trial effect: p
      < 0.001; condition effect: p = 0.611). In conclusion, all conditions elicited
      similar stress responses that transiently enhanced EX-FMD. This response may help
      to support muscle perfusion during stress. 

PMID- 24921442
TI  - Paediatric heart/heart-lung transplantation: A systemic perspective on assessment
      and preparation.
AB  - This paper is based upon our experience as a psychosocial team working on the
      paediatric heart/heart-lung (H/HLT) programme for the last 10 years. During this
      time more than 350 children have been assessed, 240 have been put onto an active
      waiting list and 160 have had transplants. The essence of this paper is a
      detailed description of the multidisciplinary and comprehensive approach to
      children who are being considered for heart or heart-lung transplantation, and
      their families. The key issues of which we have become aware are: creating a
      therapeutic alliance; listening to and involving the children; involving the
      wider network; understanding the family's illness narrative and their individual
      belief systems, including issues of culture, ethnicity and spirituality;
      acknowledging and addressing the power imbalance between the child/family and
      professional. (Int J Psych Clin Pract 2000; 4:93-99). 

PMID- 24921443
TI  - A protocol for administration of electroconvulsive therapy in elderly patients
      with fractures.
AB  - INTRODUCTION: Electroconvulsive therapy (ECT) is an important treatment for
      depressive illness in the elderly. METHOD: We describe a brief protocol, divided
      into three phases, for the administration of ECT to elderly patients with
      fractures. CONCLUSION: In conclusion, we suggest that elderly patients with
      fractures should not be denied this potentially life saving treatment. Used with
      caution ECT is both safe and effective in patients with fractures. (Int J Psych
      Clin Pract 2000; 4:101-104).

PMID- 24921444
TI  - Survey of new antidepressants in secondary care.
AB  - INTRODUCTION: There are no conclusive data to support the superior efficacy of
      any one antidepressant, while costs and side-effects are known to differ. The use
      of venlafaxine has been observed to be increasing within local services and this
      is associated with significant cost. This survey examined the patterns of use of
      new antidepressants by psychiatrists in the UK. METHOD: 188 questionnaires were
      sent to hospital pharmacists. The doses of fluoxetine, paroxetine, sertraline and
      venlafaxine used for the treatment of depression over a 1-week census period were
      recorded, together with the total quantities of each drug supplied by hospital
      pharmacies in the financial year 1997/1998. RESULTS: 84 completed replies were
      received (45%), with a total number of 2060 prescriptions for depression, making
      this the largest survey to date of antidepressant prescribing by psychiatrists.
      Fluoxetine and paroxetine were associated with less dosage titration and cost
      less per treatment month than sertraline and venlafaxine. CONCLUSION: Venlafaxine
      has not been consistently proven to be more effective than other antidepressants
      and is more costly, yet its use by psychiatrists is increasing nationally.
      Comparative data such as these are not routinely available for hospital care in
      the UK. The new NHS will bring more demand for such data and more accountability
      for its content. (Int J Psych Clin Pract 2000; 4:105-109).

PMID- 24921445
TI  - Comparative efficacy of antidepressants on anxiety features in depression: A meta
      analysis of double-blind studies of imipramine and moclobemide against placebo.
AB  - INTRODUCTION: We carried out a meta-analysis of data for 950 depressed patients
      from all double-blind, placebo-controlled comparative studies of moclobemide
      against imipramine. The aim of the analysis was to determine: 1 if the two
      antidepressants reduce anxiety symptoms as effectively as symptoms of depression;
      2. if there are differences in the anti-anxiety effects; and 3. if the severity
      of anxiety symptoms influences the outcome of treatment. METHOD: The analysis was
      done in sub-groups of patients classified according to different definitions of
      anxiety and to the degree (mild, moderate, severe) of psychic and somatic anxiety
      present at baseline. The definitions and the criteria for the severity of anxiety
      were derived from the HAMD-17 anxiety item scores (items 10 and 11) and HAMD-17
      anxiety sub-scales (ANXP and SOMA). The application of various definitions of
      anxiety (single-item and composite sub-scale scores) served to check the
      consistency, reproducibility and generalizability of the results. The criteria of
      efficacy and of the outcome of treatment, which were set in advance, were either:
      50% reduction of the HAMD anxiety sub-scale; or percentage of global improvement
      (CGEA, very much and much) at the end of treatment (4 weeks). RESULTS: The
      results showed that moclobemide and imipramine are equally effective in reducing
      psychic and somatic anxiety in depressed patients, independent of the severity of
      anxiety or how it was defined. The criterion of 50% decrease of anxiety scores
      (at week 4) was consistently reached by 60-70% of patients in all drug sub
      groups. The time course of effects on anxiety symptoms was similar with both
      drugs. It ran parallel to the regression of depression, with significant
      improvement of anxiety symptoms by week 2 on all measures. The frequency of
      benzodiazepine (BDZ) co-administration was not systematically correlated with the
      severity of anxiety. Moreover, co-prescription of BDZ did not change the outcome
      of drug treatment, with respect either to anxiety symptoms or global therapeutic
      efficacy. In placebo groups, significant negative interactions were found between
      severity of anxiety and the efficacy of treatment, which decreased with increased
      anxiety. The incidence of adverse events with moclobemide was barely higher than
      in the placebo group. Insomnia (4.9%) was the only adverse event significantly
      higher with moclobemide than with other treatments. Drop-out rates in drug groups
      were similar (27%) and unrelated to the severity of anxiety. In the placebo
      group, drop-outs were significantly higher than in drug groups (39%), and were
      positively correlated with the severity of anxiety. CONCLUSION: The results of
      this study indicate that anxiety symptoms in depressed patients respond similarly
      to moclobemide or imipramine and that the severity of these symptoms (or the co
      prescription of benzodiazepine) has no influence on either the magnitude of anti
      anxiety effects or on overall outcome. (Int J Psych Clin Pract 2000; 4:111-117).

PMID- 24921446
TI  - Non-reactive mood in outpatient depression: A 557-case study.
AB  - INTRODUCTION: The aim of the study was to find the prevalence of non-reactive
      mood in major depressive episode (MDE) outpatients, and to compare mood non
      reactive and mood reactive patients. Five hundred and fifty-seven consecutive
      unipolar and bipolar METHOD: Five hundred and fifty-seven consecutive unipolar
      and bipolar II outpatients, presenting for MDE treatment, were interviewed with
      the Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression
      Rating Scale (MADRS), and the Global Assessment of Functioning (GAF) scale.
      RESULTS: Non-reactive mood was assessed by MADRS. Non-reactive mood was present
      in 12.0% of patients. There was no significant age, gender, bipolar II, or
      unipolar difference between non-reactive and reactive mood patients, while MDE
      severity was significantly greater in non-reactive mood patients. CONCLUSION: Non
      reactive mood is uncommon among bipolar II and unipolar depressed outpatients. It
      is associated with severe depression, and the proportions of bipolar II and
      unipolar patients are not different between non-reactive and reactive mood
      patients. (Int J Psych Clin Pract 2000; 4:119-121).

PMID- 24921447
TI  - Selegiline-citalopram combination in patients with Parkinson's disease and major
      depression.
AB  - INTRODUCTION: We evaluated the efficacy and safety of the selegiline citalopram
      combination in the treatment of major depression in patients with Parkinson's
      disease. METHOD: Eight consecutive depressed outpatients who had received
      previously selegiline monotherapy or (one patient) selegiline-levodopa
      combination (the dose of selegiline was 5-10 mg/day in each case) for mild to
      severe Parkinson's disease were treated with 20 mg citalopram/day. The severity
      of depression was evaluated on the Hamilton Depression Rating Scale before and 8
      weeks after citalopram treatment. RESULTS: The majority of the patients (six)
      responded well to citalopram treatment and no adverse events occurred.
      CONCLUSION: The combination of a low dose of selegiline (5-10 mg daily) and
      citalopram (20 mg daily) may be an effective and safe method in the treatment of
      major depression in patients with Parkinson's disease. (Int J Psych Clin Pract
      2000; 4:123-125).

PMID- 24921448
TI  - Target symptoms for fluvoxamine in old age depression.
AB  - INTRODUCTION: Old age depression is difficult to treat. It is presumed that the
      underlying biochemical mechanism differs from that of depression of younger age.
      Clinical manifestations also differ, as elderly people manifest more
      irritability, anxiety, conduct and cognitive disorders than pessimism or guilt.
      Response to treatment is believed to be poorer than in younger patients. METHOD:
      Fifty patients, with a mean age of 66.65, suffering from major depression or
      dysthymia according to DSM-IV criteria, took part in the study. Their mean HDRS
      score was 16.77. They were prescribed 100 mg of fluvoxamine daily. Half of them
      returned 3 months later for reassessment by GDS, HDRS, MMSE, CAMCOG and FRSSD.
      RESULTS: Mean changes in scores were: GDS, -3.14 +/- 10.86; MMSE, -0.96 +/- 3.34;
      CAMCOG, +1.59 +/- 8.95; and FRSSD -3 +/- 4.96; statistically significant
      differences were found for GDS and FRSSD scores. All patients manifested residual
      symptoms. CONCLUSION: Fluvoxamine improved elderly patients suffering from
      geriatric depression, particularly in respect of depressive thought content (GDS)
      and impairment in everyday activities (FRSSD). When cognitive impairment due to
      depression was present, response to treatment was greater. Severely depressed
      patients showed a greater response to treatment, but also more severe residual
      symptoms. (Int J Psych Clin Pract 2000; 4:127-134) 3.17 +/- 4.06; HDRS.

PMID- 24921449
TI  - A survey of lithium monitoring and prescribing patterns.
AB  - INTRODUCTION: In the United Kingdom, guidelines for the monitoring of lithium are
      published in the British National Formulary. METHOD: Lithium monitoring and
      prescribing were retrospectively reviewed over a 6-year period in current
      patients of one General Adult Psychiatry team in Greater London. There were no
      instances of adherence to BNF guidelines at the start of treatment. RESULTS: In
      outpatients, 44% of subsequent monitoring intervals were longer than recommended
      and 10% of serum levels were above the recommended range of serum concentrations.
      Analysis of prescribing patterns by a senior pharmacist estimated 34% of the dose
      changes to have been inappropriate according to the trend of serum lithium
      levels. CONCLUSION: These results imply poor monitoring of patients on lithium,
      especially at the start of treatment. Training needs should be addressed. During
      lithium therapy, dose changes should be made with reference to previous serum
      levels. (Int J Psych Clin Pract 2000; 4:135-138).

PMID- 24921450
TI  - Risperidone compared to haloperidol in cannabis-induced psychotic disorder: A
      double blind randomized controlled trial.
AB  - INTRODUCTION: Few controlled data exist on the treatment of substancehaloperidol
      induced psychotic disorders. Our aim was to investigate the effects of
      risperidone and haloperidol. METHOD: 30 patients who met DSM-IV criteria for
      cannabis-induced psychotic disorder were randomly allocated to receive either
      risperidone or haloperidol in a 4-week randomized controlled double-blind
      clinical trial. RESULTS: There were no significant outcome differences between
      the two groups on any of the primary outcome measures, the Brief Psychiatric
      Rating Scale, Clinical Global Impression scale or the Global Assessment of
      Functioning Scale. No extrapyramidal side-effects (EPS), as measured by either
      the Simpson Angus Scale or the Barnes Akathisia Scale, emerged in the risperidone
      group; this was however not statistically different to the haloperidol group due
      to the low rate of EPS in that group. There were no significant differences
      between the two groups on the secondary outcome measures, use of lorazepam or
      biperidin. CONCLUSION: Risperidone appears to be as effective as haloperidol in
      the treatment of cannabis-induced psychotic disorder. (Int J Psych Clin Pract
      2000; 4:139-142).

PMID- 24921451
TI  - Suicide in schizophrenia: A fourteen-year survey in an English health district.
AB  - INTRODUCTION: To determine the suicide rate among patients with schizophrenia
      within the Rotherham health district and identify any possible risk factors for
      suicide in this population. METHOD: Retrospective survey of the Coroner's data
      and of the psychiatric records within both the community and hospital-based
      psychiatric services. RESULTS: Eleven suicides were identified during the years
      1984-1997 who had a diagnosis of schizophrenia. This represents a suicide rate of
      between 86 and 280 per 100 000, depending on the prevalence of schizophrenia
      within the population. This is 8-27 times as high as the rate for the general
      population of the district. CONCLUSION: Suicide in schizophrenia remains an
      uncommon event despite the increased risk. This presents problems for the
      assessment of the efficacy of suicide prevention strategies at the level of the
      average-sized health district or psychiatric department. (Int J Psych Clin Pract
      2000; 4:143-146).

PMID- 24921452
TI  - The problem of non-compliance in schizophrenia: Opinions of patients and their
      relatives. A pilot study.
AB  - INTRODUCTION: The relapse rate in patients suffering from schizophrenia is
      considerably higher than that which would be expected from the appropriate use of
      antipsychotics as prophylactic treatment. One of the reasons for this discrepancy
      is patients' non-compliance. In this study we examine reasons given by patients
      and their relatives as causes for past or possible future non-compliance. METHOD:
      Questionnaires were completed by 29 stabilized outpatients and their relatives,
      followed-up regularly (at least once per month), by the Mental Health Centre of
      Volos. RESULTS: Fifty percent of the questionnaires collected from schizophrenic
      patients (n=22) mentioned non-compliance in the past or the possibility in the
      future. Among the reasons stated by patients and their relatives in general, 60%
      had to do with lack of knowledge about the disease, and, specifically, its course
      and management; 20% had to do with lack of insight, 10% with social pressure and
      10% with drug side-effects. Overall 50% of the causes were related to the use of
      medications. The major reason for compliance (54%) was the feeling of trust in
      the doctor. CONCLUSION: Mental health professionals should be aware of the high
      potential for non-compliance, even among regular attenders of outpatient
      psychiatric clinics. Part of the solution to this problem could be the provision
      of information to patients and relatives in lay terms, aided by written
      suggestions to the doctors on how to present the information. (Int J Psych Clin
      Pract 2000; 4:147-150).

PMID- 24921453
TI  - Season-dependent symptoms in consultation-liaison patients.
AB  - INTRODUCTION: We investigated those psychiatric patients whose reason for seeking
      medical help was primarily a physical condition. Our objectives were to analyse
      to what extent they suffered from seasonal variation in mood and behaviour during
      winter, and to examine whether these patients were evenly distributed between the
      categories of the ICD-10 Classification of Mental and Behavioural Disorders (ICD
      10) by their primary diagnosis of mental disorder. METHOD: Patients attending the
      psychiatric services of a consultation liaison unit were interviewed for
      diagnosis, and were asked to fill in a questionnaire on seasonal variation in
      mood and behaviour. RESULTS: Our results suggest that there are many patients
      fulfilling the criteria based on the Seasonal Pattern Assessment uestionnaire
      (SPA) for seasonal affective disorder (SAD) or for subsyndromal SAD, not only in
      the ICD-10 diagnosis category of mood (affective) disorders but also in other
      disorder categories. CONCLUSION: This observation is of importance to hospital
      and private clinicians, as it emphasizes the need to assess the clinical picture
      in detail and to consider treatment alternatives for patients presenting with
      mental disorder with a seasonal pattern. (Int J Psych Clin Pract 2000; 4:151
      154).

PMID- 24921454
TI  - Dissociative identity disorder (DID) in Japan: A forensic case report and the
      recent increase in reports of DID.
AB  - The subject of this report murdered four young girls between 1988 and 1989. The
      forensic psychiatric evaluation showed that soon after the sudden death of his
      dearest grandfather he had developed dissociative symptoms including
      depersonalization, autoscopy, fugue, dissociative amnesia, Ganser's syndrome and
      DID, on the basis of earlier traumatic experiences under the dysfunctional family
      circumstances of his early childhood. His DID was thought to be manifest in at
      least four personalities, i.e., a host personality, a child personality, a cool
      personality and a female personality. In Japan only five cases of DID were
      reported between 1919 and 1990, whereas more than 30 cases were reported in
      journals or at academic meetings from 1991 to 1997. Although the incidence is
      still quite low in Japan, DID can be considered to be a valid clinical entity in
      spite of Merskey's severe criticism of the disorder. (Int J Psych Clin Pract
      2000; 4:155-160). 

PMID- 24921455
TI  - Manic psychosis induced by long term alpha-interferon treatment for hepatitis C.
AB  - There is increasing evidence of psychiatric side-effects following long-term
      alpha-interferon treatment, but no previous reports of psychosis as a side
      effect. There is little evidence to suggest the best treatment of
      interferonrelated psychiatric illness. A case of manic psychosis developing after
      longterm alpha-interferon treatment is reported in a woman with no previous
      psychiatric history. The patient did not respond to termination of
      alphainterferon therapy. She responded partially to olanzapine but completely
      recovered after sodium valproate was added, with no deleterious effects.
      Psychiatric side-effects, including psychosis, are appreciable problems of alpha
      interferon. This is the first case report of psychosis developing after long-term
      treatment. It supports suggestions that the pathological mechanisms of the early
      and late side-effects are different. Sodium valproate proved to be a safe and
      effective treatment. (Int J Psych Clin Pract 2000; 4:161-162). 

PMID- 24921456
TI  - Comorbidity.

PMID- 24921457
TI  - Correspondence.

PMID- 24921459
TI  - Prevalence, incidence, and lifetime risk of atrial fibrillation in China: new
      insights into the global burden of atrial fibrillation.
AB  - BACKGROUND: Much of the epidemiology of atrial fibrillation (AF) is based on data
      from Western populations. Despite the huge population of Asia, data on the
      clinical epidemiology of AF in Asian countries are limited. The current study
      aimed to investigate the prevalence and incidence of newly diagnosed (ie,
      incident) AF, as well as lifetime risk, in China and to determine the clinical
      risk factors contributing to its development. METHODS: Using a medical insurance
      database involving > 10 million individuals for the years 2001 to 2012 in the
      southwest of China, trends in incident AF were calculated using Kaplan-Meier
      analysis and Cox regression. The usefulness of the CHADS2 (congestive heart
      failure, hypertension, age, diabetes, stroke [doubled]) and CHA2DS2-VASc
      (congestive heart failure, hypertension, age >= 75 [doubled], diabetes, stroke
      [doubled], vascular disease, age 65-74, and sex category [female]) scores was
      tested in predicting the occurrence of incident AF. RESULTS: A total of 471,446
      individuals (aged >= 20 years) were studied, with 1,924,975 person-years of
      experience. We identified 921 patients with incident AF (62% male; mean age, 62
      years). The prevalence of incident AF in subjects aged >= 20 years was 0.2 per
      100 people, with an incidence of AF of 0.05 per 100 person-years overall. Over an
      11-year period, the prevalence of AF increased 20-fold, whereas AF-related stroke
      increased 13-fold. The lifetime risk of AF was approximately one in five among
      Chinese adults, and it increased with advancing age. The CHA2DS2-VASc score was
      superior to the CHADS2 score in predicting the risk of incident AF in our Chinese
      population (DeLong test, Z = 6.621, P < .001). CONCLUSIONS: The AF burden, as
      well as the risk of AF-related stroke, has increased significantly over the past
      11 years in the southwest of China. The public health burden of AF and its
      complications are greatest in the very elderly, with major implications for
      health-care systems given the global burden of this common arrhythmia.

PMID- 24921460
TI  - What role do periodontal pathogens play in osteoarthritis and periprosthetic
      joint infections of the knee?
AB  - Through the use of polymerase chain reaction (PCR)-electron spray ionization
      (ESI)-time of flight (TOF)-mass spectrometry (MS), we identified multiple
      periodontal pathogens within joint tissues of individuals undergoing replacement
      arthroplasties of the knee. The most prevalent of the periodontal pathogens were
      Treponema denticola and Enterococcus faecalis, the latter of which is commonly
      associated with apical periodontitis. These findings were unique to
      periprosthetic joint infections (PJI) of the knee and were never observed for
      PJIs of other lower extremity joints (hip and ankle) or upper extremity joints
      (shoulder and elbow). These data were confirmed by multiple independent
      methodologies including fluorescent in situ hybridization (FISH) which showed the
      bacteria deeply penetrated inside the diseased tissues, and 454-based deep 16S
      rDNA sequencing. The site-specificity, the tissue investment, and the identical
      findings by multiple nucleic-acid-based techniques strongly suggests the presence
      of infecting bacteria within these diseased anatomic sites. Subsequently, as part
      of a control program using PCR-ESI-TOF-MS, we again detected these same
      periodontal pathogens in aspirates from patients with osteoarthritis who were
      undergoing primary arthroplasty of the knee and thus who had no history of
      orthopedic implants. This latter finding raises the question of whether
      hematogenic spread of periodontal pathogens to the knee play a primary or
      secondary-exacerbatory role in osteoarthritis.

PMID- 24921461
TI  - alpha MnMoO4/graphene hybrid composite: high energy density supercapacitor
      electrode material.
AB  - A unique and cost effective hydrothermal procedure has been carried out for the
      synthesis of hexahedron shaped alpha MnMoO4 and its hybrid composite with
      graphene using three different weight percentages of graphene. Characterization
      techniques, such as XRD, Raman and FTIR analysis, established the phase and
      formation of the composite. The electrochemical characterization of the
      pseudocapacitive MnMoO4 and the MnMoO4/graphene composites in 1 M Na2SO4
      displayed highest specific capacitances of 234 F g(-1) and 364 F g(-1),
      respectively at a current density of 2 A g(-1). Unlike many other
      pseudocapacitive electrode materials our prepared materials responded in a wide
      range of working potentials of (-)1 V to (+)1 V, which indeed resulted in a high
      energy density without substantial loss of power density. The highest energy
      densities of 130 Wh kg(-1) and 202.2 Wh kg(-1) were achieved, respectively for
      the MnMoO4 and the MnMoO4/graphene composite at a constant power delivery rate of
      2000 W kg(-1). The synergistic effect of the graphene with the pseudocapacitive
      MnMoO4 caused an increased cycle stability of 88% specific capacitance retention
      after 1000 consecutive charge discharge cycles at 8 A g(-1) constant current
      density, which was higher than the virgin MnMoO4 with 84% specific capacitance
      retention. 

PMID- 24921462
TI  - Genetic epidemiology and preventive healthcare in multiethnic societies: the
      hemoglobinopathies.
AB  - Healthy carriers of severe Hemoglobinopathies are usually asymptomatic and only
      efficiently detected through screening campaigns. Based upon epidemiological
      data, screenings have been offered for decades to populations of endemic Southern
      Europe for primary prevention of Thalassemia Major, while for many populations of
      the highly endemic African and Asian countries prevention for Sickle Cell Disease
      and Thalassemia Major is mainly unavailable. The massive migrations of the last
      decades have brought many healthy carriers of these diseases to live and
      reproduce in non-endemic immigration areas changing the epidemiological pattern
      of the local recessive diseases and bringing an urgent need for treatment and
      primary prevention in welfare countries. Nonetheless, no screening for an
      informed reproductive choice is actively offered by the healthcare systems of
      most of these welfare countries. As a consequence more children affected with
      severe Hemoglobinopathies are born today in the immigration countries of Northern
      Europe than in the endemic Southern European area. Following the Mediterranean
      example, some countries like the UK and The Netherlands have been offering early
      pregnancy carrier screening at different levels and/or in specific areas but more
      accessible measures need to be taken at the national level in all immigration
      countries. Identification of carriers using simple and inexpensive methods should
      be included in the Rhesus and infectious diseases screening which is offered
      early in pregnancy in most developed countries. This would allow identification
      of couples at risk in time for an informed choice and for prenatal diagnosis if
      required before the first affected child is born. 

PMID- 24921464
TI  - Mycobacterium chelonae keratitis in a 3-decade-old corneal graft.

PMID- 24921463
TI  - Parity, age at first birth, and risk of death from asthma: evidence from a cohort
      in taiwan.
AB  - This study was undertaken to examine whether there is an association between age
      at first birth and parity and risk of asthma death. The study cohort consisted of
      1,292,462 women in Taiwan who had a first live birth between 1 January 1978 and
      31 December 1987. We tracked each woman from the date of their first childbirth
      to 31 December 2009, and their vital status was ascertained by linking records
      with the computerized mortality database. Cox proportional hazard regression
      models were used to estimate hazard ratios of death from asthma associated with
      parity and age at first birth. A trend of increasing risk of asthma death was
      seen with increasing age at first birth. The adjusted hazard ratio was 0.75 (95%
      confidence interval (CI) = 0.53-1.08) among women with two live births and 0.53
      (95% CI = 0.36-0.78) among those with three or more births, compared with women
      who had one live birth. There was a significant decreasing trend in adjusted
      hazard ratios of asthma death with increasing parity. This study is the first to
      provide evidences to support an association between reproductive factors (parity
      and early age at first birth) and the risk of asthma death. 

PMID- 24921465
TI  - AAC Editor's Awards for 2013.

PMID- 24921466
TI  - Increasing hybridization rate and sensitivity of DNA microarrays using
      isotachophoresis.
AB  - We present an on-chip electrokinetic method to increase the reaction kinetics and
      sensitivity of DNA microarray hybridization. We use isotachophoresis (ITP) to
      preconcentrate target molecules in solution and transport them over the
      immobilized probe sites of a microarray, greatly increasing the binding reaction
      rate. We show theoretically and experimentally that ITP-enhanced microarrays can
      be hybridized much faster and with higher sensitivity than conventional methods.
      We demonstrate our assay using a microfluidic system consisting of a PDMS
      microchannel superstructure bonded onto a glass slide on which 60 spots of 20-27
      nt ssDNA oligonucleotide probes are immobilized. Our 30 min assay results in an
      8.2 fold higher signal than the conventional overnight hybridization at 100 fM
      target concentration. We show rapid and quantitative detection over 4 orders of
      magnitude dynamic range of target concentration with no increase in the
      nonspecific signal. Our technique can be further multiplexed for higher density
      microarrays and extended for other reactions of target-surface immobilized
      ligands. 

PMID- 24921467
TI  - Emergent properties arising from the assembly of amphiphiles. Artificial vesicle
      membranes as reaction promoters and regulators.
AB  - This article deals with artificial vesicles and their membranes as reaction
      promoters and regulators. Among the various molecular assemblies which can form
      in an aqueous medium from amphiphilic molecules, vesicle systems are unique.
      Vesicles compartmentalize the aqueous solution in which they exist, independent
      on whether the vesicles are biological vesicles (existing in living systems) or
      whether they are artificial vesicles (formed in vitro from natural or synthetic
      amphiphiles). After the formation of artificial vesicles, their aqueous interior
      (the endovesicular volume) may become - or may be made - chemically different
      from the external medium (the exovesicular solution), depending on how the
      vesicles are prepared. The existence of differences between endo- and
      exovesicular composition is one of the features on the basis of which biological
      vesicles contribute to the complex functioning of living organisms. Furthermore,
      artificial vesicles can be formed from mixtures of amphiphiles in such a way that
      the vesicle membranes become molecularly, compositionally and organizationally
      highly complex, similarly to the lipidic matrix of biological membranes. All the
      various properties of artificial vesicles as membranous compartment systems
      emerge from molecular assembly as these properties are not present in the
      individual molecules the system is composed of. One particular emergent property
      of vesicle membranes is their possible functioning as promoters and regulators of
      chemical reactions caused by the localization of reaction components, and
      possibly catalysts, within or on the surface of the membranes. This specific
      feature is reviewed and highlighted with a few selected examples which range from
      the promotion of decarboxylation reactions, the selective binding of DNA or RNA
      to suitable vesicle membranes, and the reactivation of fragmented enzymes to the
      regulation of the enzymatic synthesis of polymers. Such type of emergent
      properties of vesicle membranes may have been important for the prebiological
      evolution of protocells, the hypothetical compartment systems preceding the first
      cells in those chemical and physico-chemical processes that led to the origin of
      life. 

PMID- 24921468
TI  - Modeling a measurement-device-independent quantum key distribution system.
AB  - We present a detailed description of a widely applicable mathematical model for
      quantum key distribution (QKD) systems implementing the measurement-device
      independent (MDI) protocol. The model is tested by comparing its predictions with
      data taken using a proof-of-principle, time-bin qubit-based QKD system in a
      secure laboratory environment (i.e. in a setting in which eavesdropping can be
      excluded). The good agreement between the predictions and the experimental data
      allows the model to be used to optimize mean photon numbers per attenuated laser
      pulse, which are used to encode quantum bits. This in turn allows optimization of
      secret key rates of existing MDI-QKD systems, identification of rate-limiting
      components, and projection of future performance. In addition, we also performed
      measurements over deployed fiber, showing that our system's performance is not
      affected by environment-induced perturbations. 

PMID- 24921469
TI  - Effective absorption enhancement in dielectric thin-films with embedded paired
      strips gold nanoantennas.
AB  - This study focuses on determining the optimized thickness of an absorbing thin
      film with embedded gold nanoantennas, for absorption enhancement. Gold paired
      strips nanoantennas with small gaps have been proposed for light trapping because
      of the high localized electric field in the gap due to resonance. Paired-strips
      nanoantennas with small gaps produce higher effective absorption compared to
      single-strip gratings. From the average absorption two-dimensional map, the
      absorption enhancement may increase by a factor of up to 20 for gold paired
      strips nanoantennas embedded in a 100 nm thick P3HT:PCBM thin-film. 

PMID- 24921470
TI  - Backward stimulated radiation from filaments in nitrogen gas and air pumped by
      circularly polarized 800 nm femtosecond laser pulses.
AB  - We report on strong backward stimulated emission at 337 nm in nitrogen gas pumped
      by circularly polarized femtosecond laser pulses at 800 nm. A distinct dependence
      of the backward UV spectrum on pump laser polarization and intensity is observed,
      pointing to the occurrence of backward amplified spontaneous emission inside
      filaments. We attribute the population inversion to inelastic collision between
      the free electrons produced by the pump laser and neutral N2 molecules. The
      addition of oxygen molecules is detrimental for the gain, reducing it to near
      threshold at atmospheric concentration.

PMID- 24921471
TI  - Electromagnetic energy transport in finite photonic structures.
AB  - We have derived, for oblique propagation, an equation relating the averaged
      energy flux density to energy fluxes arising in the process of scattering by a
      lossless finite photonic structure. The latter fluxes include those associated
      with the dispersion relation of the structure, reflection, and interference
      between the incident and reflected waves. We have also derived an explicit
      relation between the energy flux density and the group velocity, which provides a
      simple and systematical procedure for studying theoretically and experimentally
      the properties of the energy transport through a wide variety of finite photonic
      structures. Such a relation may be regarded as a generalization of the
      corresponding one for infinite periodic systems to finite photonic structures. A
      finite, N-period, photonic crystal was used to illustrate the usefulness of our
      results. 

PMID- 24921472
TI  - Fast feature identification for holographic tracking: the orientation alignment
      transform.
AB  - The concentric fringe patterns created by features in holograms may be associated
      with a complex-valued orientational order field. Convolution with an
      orientational alignment operator then identifies centers of symmetry that
      correspond to the two-dimensional positions of the features. Feature
      identification through orientational alignment is reminiscent of voting
      algorithms such as Hough transforms, but may be implemented with fast convolution
      methods, and so can be orders of magnitude faster. 

PMID- 24921473
TI  - A scalable and continuous-upgradable optical wireless and wired convergent access
      network.
AB  - In this work, a scalable and continuous upgradable convergent optical access
      network is proposed. By using a multi-wavelength coherent comb source and a
      programmable waveshaper at the central office (CO), optical millimeter-wave (mm
      wave) signals of different frequencies (from baseband to > 100 GHz) can be
      generated. Hence, it provides a scalable and continuous upgradable solution for
      end-user who needs 60 GHz wireless services now and > 100 GHz wireless services
      in the future. During the upgrade, user only needs to upgrade their optical
      networking unit (ONU). A programmable waveshaper is used to select the suitable
      optical tones with wavelength separation equals to the desired mm-wave frequency;
      while the CO remains intact. The centralized characteristics of the proposed
      system can easily add any new service and end-user. The centralized control of
      the wavelength makes the system more stable. Wired data rate of 17.45 Gb/s and w
      band wireless data rate up to 3.36 Gb/s were demonstrated after transmission over
      40 km of single-mode fiber (SMF). 

PMID- 24921474
TI  - Demonstration of a broad band spectral head-mounted display with freeform
      mirrors.
AB  - It has been demonstrated that electrical stimulation of the retina can produce
      visual perception for blind patients suffering from macular degeneration and
      retinitis pigmentosa. In order to let the retinal chip generate enough electrical
      stimulation, the near infrared ray source is added to enhance the stimulation
      current. However, it is a challenge to design a head-mounted display (HMD) that
      covers both visible and infrared rays. Since the HMD system covers such a broad
      spectral band, large color aberrations will be induced. In order to eliminate
      these large aberrations, a mirror system is adopted that will create a no color
      aberration system. We also use two freeform mirrors (FFMs) to reduce residual
      aberrations such as spherical aberrations and coma. The FFMs serve as the near
      eye viewing optics that magnifies the image which is displayed through a
      microdisplay. Based on a 0.61 in. microdisplay, the HMD system demonstrates a
      diagonal field of view (FOV) of 30 degree and an f/# of 3.75, with an exit pupil
      diameter of 8 mm and eye clearance of 15mm. 

PMID- 24921475
TI  - Improved 8-channel silicon mode demultiplexer with grating polarizers.
AB  - An improved 8-channel silicon mode demultiplexer is realized with TE-type and TM
      type grating polarizers at the output ends, and these gratings serve as fiber
      chip couplers simultaneously. The present 8-channel silicon mode demultiplexer
      includes a three-waveguide PBS (for separating the TE0 and TM0 modes) and six
      cascaded ADCs (for demultiplexing the high-order modes of both polarizations).
      The grating polarizers with high extinction ratios are used to filter out the
      polarization crosstalk in the 8-channel hybrid multiplexer efficiently and the
      measured crosstalk for all the mode-channels of the improved 8-channel mode
      multiplexer is reduced greatly to ~-20dB in a ~100nm bandwidth.

PMID- 24921476
TI  - Bio-inspired, sub-wavelength surface structures for ultra-broadband, omni
      directional anti-reflection in the mid and far IR.
AB  - Quasi-ordered moth-eye arrays were fabricated in Si using a colloidal lithography
      method to achieve highly efficient, omni-directional transmission of mid and far
      infrared (IR) radiation. The effect of structure height and aspect ratio on
      transmittance and scattering was explored experimentally and modeled
      quantitatively using effective medium theory. The highest aspect ratio structures
      (AR = 9.4) achieved peak transmittance of 98%, with >85% transmission for lambda
      = 7-30 MUm. A detailed photon balance was constructed by measuring transmission,
      forward scattering, specular reflection and diffuse reflection to quantify
      optical losses due to near-field effects. In addition, angle-dependent
      transmission measurements showed that moth-eye structures provide superior anti
      reflective properties compared to unstructured interfaces over a wide angular
      range (0-60 degrees  incidence). The colloidal lithography method presented here
      is scalable and substrate-independent, providing a general approach to realize
      moth-eye structures and anti-reflection in many IR-compatible material systems. 

PMID- 24921477
TI  - A 23-watt single-frequency vertical-external-cavity surface-emitting laser.
AB  - We report on a single-frequency semiconductor disk laser which generates 23.6 W
      output power in continuous wave operation, at a wavelength of 1013 nm. The high
      output power is a result of optimizing the chip design, thermal management and
      the cavity configuration. By applying passive stabilization techniques, the free
      running linewidth is measured to be 407 kHz for a sampling time of 1 ms, while
      undercutting 100 kHz in the microsecond domain. 

PMID- 24921478
TI  - Dispersion insensitive optical signal to noise ratio monitoring of PDM signal by
      using uncorrelated signal power.
AB  - In this paper, we propose and demonstrate optical signal to noise ratio (OSNR)
      monitoring method for polarization-division-multiplexing (PDM) signal by using
      the uncorrelated signal power, which is generated by balanced subtraction in
      electrical domain. The proposed OSNR monitoring is insensitive to dispersion
      impairment by using low bandwidth receiver. The proposed OSNR monitoring method
      is tested from 5 dB to 27.5 dB in 100-Gb/s PDM-QPSK system experimentally. 

PMID- 24921479
TI  - Ultraviolet vortex generation using periodically bonded beta-BaB2O4 device.
AB  - This paper describes the first demonstration of ultraviolet (266nm) vortex
      generation using the combination of a frequency-doubled nanosecond green laser, a
      spiral phase plate, and a periodically bonded beta-BaB2O4 device. For a laser
      pumping energy of 9.1 mJ, an ultraviolet vortex energy of 1.24 mJ was obtained,
      corresponding to a conversion efficiency of 13.7%.

PMID- 24921480
TI  - Generation of quasi-monoenergetic electron beams with small normalized
      divergences angle from a 2 TW laser facility.
AB  - We report the generation of a 6 pC, 23 MeV electron bunch with the energy spread
      +/- 3.5% by using 2 TW, 80 fs high contrast laser pulses interacting with helium
      gas targets. Within the optimized experimental condition, we obtained quasi
      monoenergetic electron beam with an ultra-small normalized divergence angle of 92
      mrad, which is at least 5 times smaller than the previous LPA-produced bunches.
      We suggest the significant decrease of the normalized divergence angles is due to
      smooth transfer from SM-LWFA to LWFA. Since the beam size in LPA is typically
      small, this observation may explore a simple way to generate ultralow normalized
      emittance electron bunches by using small-power but high-repetition-rate laser
      facilities. 

PMID- 24921481
TI  - High speed switching between arbitrary spatial light profiles.
AB  - Complex images, inscribed into the spatial profile of a laser beam or even a
      single photon, offer a highly efficient method of data encoding. Here we present
      a prototype system which can quickly modulate between arbitrary images. We
      display an array of holograms, each defined by its phase and intensity profile,
      on a spatial light modulator. The input beam is then steered by an acousto-optic
      modulator to one of these holograms, where it is converted into the desired light
      mode. We demonstrate switching between characters within three separate alphabets
      at a switching rate of up to10 kHz. This rate is limited by our detection system,
      and we anticipate that the system is capable of far higher rates. Furthermore our
      system is not limited in efficiency by channel number, making it ideal for
      quantum communication applications. 

PMID- 24921482
TI  - Photonic crystal based microscale flow cytometry.
AB  - Here we propose a new design of an on-chip micro-flow cytometry based on photonic
      crystals. When individual cells flow tangential to the crystal surface, the
      transmission of the light through the photonic crystal changes depending on the
      presence or absence of the cells and their size and shape. This system was
      modeled using OptiFDTD, where transmission spectra were extracted. Initially, the
      potential for cell counting has been demonstrated. Then, for cells with differing
      shape a direct relation between signal distribution and cell shape has been
      found. 

PMID- 24921483
TI  - All-optical XOR logic gate using intersubband transition in III-V quantum well
      materials.
AB  - A monolithically integrated all-optical exclusive-OR (XOR) logic gate is
      experimentally demonstrated based on a Michelson interferometer (MI) gating
      device in InGaAs/AlAsSb coupled double quantum wells (CDQWs). The MI arms can
      convert the pump data with return-to-zero ON-OFF keying (RZ OOK) to binary phase
      shift keying (BPSK) format, then two BPSK signals can interfere with each other
      for realizing a desired logical operation. All-optical format conversion from the
      RZ OOK to BPSK is based on the cross-phase modulation to the transverse electric
      (TE) probe wave, which is caused by the intersubband transition excited by the
      transverse magnetic (TM) pump light. Bit error rate measurements show that error
      free operation for both BPSK format conversion and XOR logical operation can be
      achieved. 

PMID- 24921485
TI  - Passive mode locking of ytterbium- and erbium-doped all-fiber lasers using
      graphene oxide saturable absorbers.
AB  - Broadband graphene oxide/PVA films were used as saturable absorbers (SAs) for
      mode locking erbium-doped fiber laser (EDFL) and ytterbium-doped fiber laser
      (YDFL) at 1.06 MUm and 1.55 MUm. They provide modulation depths of 3.15% and 6.2%
      for EDFL and YDFL, respectively. Stable self-starting mode-locked pulses are
      obtained for both lasers, confirming that the graphene oxide is cost-effective.
      We have generated mode-locked pulses with spectral width, repetition rate, and
      pulse duration of 0.75 nm, 9.5 MHz, and 2.7 ps. This is the shortest pulse
      duration directly obtained from an all-normal-dispersion YDFL with graphene-oxide
      saturable absorber. 

PMID- 24921486
TI  - Super-resolution coherent anti-Stokes Raman scattering microscopy with photonic
      nanojets.
AB  - We demonstrate far-field super-resolution coherent anti-Stokes Raman scattering
      (CARS) microscopy by exciting the sample with photonic nanojets. The sub
      diffraction photonic nanojets were formed on the surface of the sample by
      microspheres illuminated by laser beams, and images were acquired by a standard
      laser-scanning CARS microscope. When the laser beams were focused on the
      microspheres, the photonic nanojets determined the excitation volume instead of
      the diffraction-limited laser foci, leading to super-resolution. We imaged the
      sub-diffraction features of a Blu-ray disc using glass spheres with a refractive
      index of 1.46 and diameters in the 1-6 um range. The microspheres provided a
      lateral magnification factor up to 5.0X and a lateral resolution of at least 200
      nm at 796 nm laser wavelength, allowing us to resolve the features on the disc
      which were invisible under normal CARS imaging. The magnification factor depended
      on both the microsphere size and the focal plane position of the incident beams.
      To explain the magnification factor we performed theoretical simulations which
      showed excellent agreement with experimental results. This super-resolution
      technique could be very useful for the vibrational imaging of nano-scale objects
      on films and surfaces. 

PMID- 24921484
TI  - Towards jitter-free pump-probe measurements at seeded free electron laser
      facilities.
AB  - X-ray free electron lasers (FEL) coupled with optical lasers have opened
      unprecedented opportunities for studying ultrafast dynamics in matter. The major
      challenge in pump-probe experiments using FEL and optical lasers is synchronizing
      the arrival time of the two pulses. Here we report a technique that benefits from
      the seeded-FEL scheme and uses the optical seed laser for nearly jitter-free pump
      probe experiments. Timing jitter as small as 6 fs has been achieved and confirmed
      by measurements of FEL-induced transient reflectivity changes of Si3N4 using both
      collinear and non-collinear geometries. Planned improvements of the experimental
      set-up are expected to further reduce the timing jitter between the two pulses
      down to fs level.

PMID- 24921487
TI  - Efficient lasing in continuous wave and graphene Q-switched regimes from Nd:YAG
      ridge waveguides produced by combination of swift heavy ion irradiation and
      femtosecond laser ablation.
AB  - We report on the continuous wave and passively Q-switched lasers in Nd:YAG ridge
      waveguides fabricated by a combination of swift Kr ion irradiation and
      femtosecond laser ablation. Owing to the deep penetration length (~50 MUm) of 670
      MeV Kr(8+) ions into the crystal, ridge waveguides with large-area cross section,
      supporting nearly symmetric guiding modes, were produced. Continuous wave lasers
      with maximum 182 mW output power at ~1064 nm have been realized at 808-nm optical
      pump. Using graphene as a saturable absorber, passively Q-switched waveguide
      laser operations were achieved. The pulsed laser produces 90 ns pulses, with a
      ~4.2 MHz repetition rate, 19% slope efficiency and 110 mW average output power,
      corresponding to single-pulse energy of 26.5 nJ.

PMID- 24921488
TI  - Combination of cylindrical confinement and spark discharge for signal improvement
      using laser induced breakdown spectroscopy.
AB  - Spark discharge has been proved to be an effective way to enhance the LIBS signal
      while moderate cylindrical confinement is able to increase the signal
      repeatability with limited signal enhancement effects. In the present work, these
      two methods were combined together not only to improve the pulse-to-pulse signal
      repeatability but also to simultaneously and significantly enhance the signal as
      well as SNR. Plasma images showed that the confinement stabilized the morphology
      of the plasma, especially for the discharge assisted process, which explained the
      improvement of the signal repeatability. 

PMID- 24921489
TI  - Optically trapped mirror for reaching the standard quantum limit.
AB  - The preparation of a mechanical oscillator driven by quantum back-action is a
      fundamental requirement to reach the standard quantum limit (SQL) for force
      measurement, in optomechanical systems. However, thermal fluctuating force
      generally dominates a disturbance on the oscillator. In the macroscopic scale, an
      optical linear cavity including a suspended mirror has been used for the weak
      force measurement, such as gravitational-wave detectors. This configuration has
      the advantages of reducing the dissipation of the pendulum (i.e., suspension
      thermal noise) due to a gravitational dilution by using a thin wire, and of
      increasing the circulating laser power. However, the use of the thin wire is weak
      for an optical torsional anti-spring effect in the cavity, due to the low
      mechanical restoring force of the wire. Thus, there is the trade-off between the
      stability of the system and the sensitivity. Here, we describe using a triangular
      optical cavity to overcome this limitation for reaching the SQL. The triangular
      cavity can provide a sensitive and stable system, because it can optically trap
      the mirror's motion of the yaw, through an optical positive torsional spring
      effect. To show this, we demonstrate a measurement of the torsional spring effect
      caused by radiation pressure forces. 

PMID- 24921491
TI  - Impact of lithography on the fluorescence dynamics of self-assembled
      fluorophores.
AB  - Micro- and nano-patterned fluorescent materials are important for many photonic
      devices and applications. In this paper, we investigate the impact of three
      common lithographical techniques, deposition and removal of sacrificial masks,
      ultraviolet ablation, and focused ion beam milling, on self-assembled
      fluorophores. We find that different patterning techniques can dramatically
      change the fluorescence lifetime of the fluorophores and that the degree of
      modification depends on the patterning techniques. 

PMID- 24921490
TI  - Fizeau interferometric cophasing of segmented mirrors: experimental validation.
AB  - We present an optical testbed demonstration of the Fizeau Interferometric
      Cophasing of Segmented Mirrors (FICSM) algorithm. FICSM allows a segmented mirror
      to be phased with a science imaging detector and three filters (selected among
      the normal science complement). It requires no specialised, dedicated wavefront
      sensing hardware. Applying random piston and tip/tilt aberrations of more than 5
      wavelengths to a small segmented mirror array produced an initial unphased point
      spread function with an estimated Strehl ratio of 9% that served as the starting
      point for our phasing algorithm. After using the FICSM algorithm to cophase the
      pupil, we estimated a Strehl ratio of 94% based on a comparison between our data
      and simulated encircled energy metrics. Our final image quality is limited by the
      accuracy of our segment actuation, which yields a root mean square (RMS)
      wavefront error of 25 nm. This is the first hardware demonstration of coarse and
      fine phasing an 18-segment pupil with the James Webb Space Telescope (JWST)
      geometry using a single algorithm. FICSM can be implemented on JWST using any of
      its scientic imaging cameras making it useful as a fall-back in the event that
      accepted phasing strategies encounter problems. We present an operational
      sequence that would co-phase such an 18-segment primary in 3 sequential
      iterations of the FICSM algorithm. Similar sequences can be readily devised for
      any segmented mirror. 

PMID- 24921492
TI  - Wavelength conversion of incoherent light by sum-frequency generation.
AB  - In this paper, we reveal that some kinds of optical nonlinearities are further
      enhanced when incoherent light, instead of a laser, is used as a pump light. This
      idea was confirmed both theoretically and experimentally in the case of sum
      frequency generation (SFG) using the optical second nonlinearity. The conversion
      efficiency of the SFG with incoherent light pumping increased as the bandwidth of
      the incoherent pump light decreased, finally reaching twice the conversion
      efficiency of conventional second harmonic generation (SHG) by laser pumping.
      This method dramatically relaxes the severe requirements of phase matching in the
      nonlinear optical process. The conversion efficiency became less sensitive to
      misalignment of the wavelength of pump light and also of device operation
      temperature when the bandwidth of the incoherent pump light was sufficiently
      broad, although the improvement of the conversion efficiency had an inverse
      relationship with the insensitivity to the phase-matching condition. The
      temperature tuning range was enhanced by more than two orders of magnitude in
      comparison with the conventional SHG method. As an example of a promising
      application of this new idea, we performed the generation of quantum entangled
      photon-pairs using cascaded optical nonlinearities (SFG and the subsequent
      spontaneous parametric down conversion) in a single periodically poled LiNbO3
      waveguide device, in which the incoherent light was used as the pump source for
      both the parametric processes. We have achieved high fidelity exceeding 99% in
      quantum-state tomography experiments.

PMID- 24921493
TI  - Gradient index lens based combined two-photon microscopy and optical coherence
      tomography.
AB  - We report a miniaturized probe-based combined two-photon microscopy (TPM) and
      optical coherence tomography (OCT) system. This system is to study the colorectal
      cancer in mouse models by visualizing both cellular and structural information of
      the colon in 3D with TPM and OCT respectively. The probe consisted of gradient
      index (GRIN) lenses and a 90 degrees  reflecting prism at its distal end for side
      viewing, and it was added onto an objective lens-based TPM and OCT system. The
      probe was 2.2 mm in diameter and 60 mm in length. TPM imaging was performed by
      raster scanning of the excitation focus at the imaging speed of 15.4 frames/s.
      OCT imaging was performed by combining the linear sample translation and probe
      rotation along its axis. This miniaturized probe based dual-modal system was
      characterized with tissue phantoms containing fluorescent microspheres, and
      applied to image mouse colonic tissues ex vivo as a demonstration. As OCT and TPM
      provided structural and cellular information of the tissues respectively, this
      probe based multi-modal imaging system can be helpful for in vivo studies of
      preclinical animal models such as mouse colonic tumorigenesis. 

PMID- 24921494
TI  - Sensitivity analysis and optimization of sub-wavelength optical gratings using
      adjoints.
AB  - Numerical optimization of photonic devices is often limited by a large design
      space the finite-differences gradient method requires as many electric field
      computations as there are design parameters. Adjoint-based optimization can
      deliver the same gradients with only two electric field computations. Here, we
      derive the relevant adjoint formalism and illustrate its application for a
      waveguide slab, and for the design of optical sub-wavelength gratings. 

PMID- 24921495
TI  - Multichannel terahertz time-domain spectroscopy system at 1030 nm excitation
      wavelength.
AB  - We present Terahertz (THz) imaging with a 1D multichannel time-domain
      spectroscopy (TDS) system which operates with a photoconductive array of 15
      detection channels excited by a 1030 nm femtosecond fiber laser. The emitter and
      detector are photoconductive antennas based on InGaAs/InAlAs multi-layer
      heterostructures (MLHS). We characterized the THz optics and the resolution of
      the system. The performance is demonstrated by the multichannel imaging of two
      samples. A simultaneous measurement of 15 THz pulses with a pixel pitch of 1 mm
      increases the measurement speed of the TDS system by factor 15. 

PMID- 24921496
TI  - Beam shaping for laser-based adaptive optics in astronomy.
AB  - The availability and performance of laser-based adaptive optics (AO) systems are
      strongly dependent on the power and quality of the laser beam before being
      projected to the sky. Frequent and time-consuming alignment procedures are
      usually required in the laser systems with free-space optics to optimize the
      beam. Despite these procedures, significant distortions of the laser beam have
      been observed during the first two years of operation of the Gemini South multi
      conjugate adaptive optics system (GeMS). A beam shaping concept with two
      deformable mirrors is investigated in order to provide automated optimization of
      the laser quality for astronomical AO. This study aims at demonstrating the
      correction of quasi-static aberrations of the laser, in both amplitude and phase,
      testing a prototype of this two-deformable mirror concept on GeMS. The paper
      presents the results of the preparatory study before the experimental phase. An
      algorithm to control amplitude and phase correction, based on phase retrieval
      techniques, is presented with a novel unwrapping method. Its performance is
      assessed via numerical simulations, using aberrations measured at GeMS as
      reference. The results predict effective amplitude and phase correction of the
      laser distortions with about 120 actuators per mirror and a separation of 1.4 m
      between the mirrors. The spot size is estimated to be reduced by up to 15% thanks
      to the correction. In terms of AO noise level, this has the same benefit as
      increasing the photon flux by 40%. 

PMID- 24921497
TI  - Tests of a compact static Fourier-transform imaging spectropolarimeter.
AB  - A compact Fourier-transform imaging spectropolarimeter covering a 450-1000 nm
      spectral range is presented. The sensor, which is based on two birefringent
      retarders and a Wollaston interferometer, offers significant advantages over
      previous implementations. Specifically, with no internal moving parts,
      electrically controllable or micro polarization components, the full wavelength
      dependent state of polarization, spectral and spatial information of a scene can
      be acquired simultaneously. Outdoor measurements of several cars and plants
      demonstrate the sensor's potential for color measurement, target identification,
      and agriculture monitoring applications. 

PMID- 24921498
TI  - Sensitization of Er3+ ions in silicon rich oxynitride films: effect of thermal
      treatments.
AB  - The optical properties of reactive co-sputtered erbium doped silicon rich
      oxynitride (Er:SRON) films are studied as a function of annealing temperatures
      (Ta). The sensitization mechanism of Er3+ is found to evolve with Ta: excess Si
      related localized states play the essential role in samples when Ta is below 700 
      degrees C, while silicon nanoclusters (Si-NCs) become the dominate sensitizers
      when Ta exceeds 800  degrees C. Our results show that higher density of
      sensitized Er3+ could be acquired via energy transfer from localized states, and
      thus provide an alternative way for the engineering of light sources based on
      Er:SRON.

PMID- 24921499
TI  - Light sources generating self-splitting beams and their propagation in non
      Kolmogorov turbulence.
AB  - A class of random sources producing far fields self-splitting intensity profiles
      with variable spacing between the x and y directions is introduced. The beam
      conditions for ensuring the sources to generate a beam are derived. Based on the
      derived analytical expression, the evolution behavior of the beams produced by
      these families of sources in free space and turbulence atmospheric are explored
      and comparatively analyzed. By changing the modulation parameters n and m, the
      degree of coherence of Gaussian Schell-model source in the x and y directions are
      modulated respectively, and then the number of splitting beams and the spacing
      between splitting beams can be adjusted. It is illustrated that the self
      splitting intensity profile is stable when beams propagate in free space, but
      they eventually transformed into a Gaussian profiles when it passes at
      sufficiently large distances from its source through the turbulent atmosphere. 

PMID- 24921501
TI  - Energy-efficient optical network units for OFDM PON based on time-domain
      interleaved OFDM technique.
AB  - We propose and experimentally demonstrate a new scheme to reduce the energy
      consumption of optical network units (ONUs) in orthogonal frequency division
      multiplexing passive optical networks (OFDM PONs) by using time-domain
      interleaved OFDM (TI-OFDM) technique. In a conventional OFDM PON, each ONU has to
      process the complete downstream broadcast OFDM signal with a high sampling rate
      and a large FFT size to retrieve its required data, even if it employs a portion
      of OFDM subcarriers. However, in our scheme, the ONU only needs to sample and
      process one data group from the downlink TI-OFDM signal, effectively reducing the
      sampling rate and the FFT size of the ONU. Thus, the energy efficiency of ONUs in
      OFDM PONs can be greatly improved. A proof-of-concept experiment is conducted to
      verify the feasibility of the proposed scheme. Compared to the conventional OFDM
      PON, our proposal can save 17.1% and 26.7% energy consumption of ONUs by halving
      and quartering the sampling rate and the FFT size of ONUs with the use of the TI
      OFDM technology. 

PMID- 24921502
TI  - Multipass laser cavity for efficient transverse illumination of an elongated
      volume.
AB  - A multipass laser cavity is presented which can be used to illuminate an
      elongated volume from a transverse direction. The illuminated volume can also
      have a very large transverse cross section. Convenient access to the illuminated
      volume is granted. The multipass cavity is very robust against misalignment, and
      no active stabilization is needed. The scheme is suitable for example in beam
      experiments, where the beam path must not be blocked by a laser mirror, or if the
      illuminated volume must be very large. This cavity was used for the muonic
      hydrogen experiment in which 6 MUm laser light illuminated a volume of 7 * 25 *
      176 mm3, using mirrors that are only 12 mm in height. We present our measurement
      of the intensity distribution inside the multipass cavity and show that this is
      in good agreement with our simulation.

PMID- 24921503
TI  - Temperature characteristics of surface micromachined MEMS-VCSEL with large tuning
      range.
AB  - Several Applications for tunable laser diodes have strict constraints in terms of
      overall power consumption. Furthermore, the implementation in harsh environments
      with large temperature fluctuations is necessary. Due to the constraint in power
      consumption, the application of active cooling might not be an option. For this
      reason we investigate the temperature characteristics of an electrically pumped
      MEMS-VCSEL with wide continuous wavelength tuning. For the first time, a mode hop
      free single mode (side mode suppression ratio (SMSR) > 40dB) tuning range of 45nm
      at 70 degrees C is demonstrated with a MEMS-VCSEL. An increase of the tuning
      range from 85nm at 20 degrees C to 92nm at 40 degrees C is measured and
      explained. In contrast to fixed wavelength VCSEL, the investigated device shows a
      negative temperature induced wavelength shift of -4.5nmK(-1), which is caused by
      the MEMS-mirror. At 1560nm, the fibre-coupled optical output power is above 0.6mW
      over the entire temperature range between 20 degrees C to 70 degrees C and shows
      a maximum of > 3mW at 20 degrees C.

PMID- 24921504
TI  - Scanning inverse fluorescence correlation spectroscopy.
AB  - Scanning Inverse Fluorescence Correlation Spectroscopy (siFCS) is introduced to
      determine the absolute size of nanodomains on surfaces. We describe here
      equations for obtaining the domain size from cross- and auto-correlation
      functions, measurement simulations which enabled testing of these equations, and
      measurements on model surfaces mimicking membranes containing nanodomains. Using
      a confocal microscope of 270 nm resolution the size of 250 nm domains were
      estimated by siFCS to 257 +/- 12 nm diameter, and 40 nm domains were estimated to
      65 +/- 26 nm diameter. Applications of siFCS for sizing of nanodomains and
      protein clusters in cell membranes are discussed. 

PMID- 24921505
TI  - Large-mode-area infrared guiding in ultrafast laser written waveguides in sulfur
      based chalcogenide glasses.
AB  - Current demands in astrophotonics impose advancing optical functions in infrared
      domains within embedded refractive index designs. We demonstrate concepts for
      large-mode-area guiding in ultrafast laser photowritten waveguides in bulk Sulfur
      based chalcogenide glasses. If positive index contrasts are weak in As2S3, Ge
      doping increases the matrix rigidity and allows for high contrast (10(-3))
      positive refractive index changes. Guiding with variable mode diameter and large
      mode-area light transport is demonstrated up to 10 MUm spectral domain using
      transverse slit-shaped and evanescently-coupled multicore traces.

PMID- 24921506
TI  - Focused ion beam post-processing of optical fiber Fabry-Perot cavities for
      sensing applications.
AB  - Focused ion beam technology is combined with chemical etching of specifically
      designed fibers to create Fabry-Perot interferometers. Hydrofluoric acid is used
      to etch special fibers and create microwires with diameters of 15 MUm. These
      microwires are then milled with a focused ion beam to create two different
      structures: an indented Fabry-Perot structure and a cantilever Fabry-Perot
      structure that are characterized in terms of temperature. The cantilever
      structure is also sensitive to vibrations and is capable of measuring frequencies
      in the range 1 Hz - 40 kHz. 

PMID- 24921507
TI  - Assessment of the colored dissolved organic matter in coastal waters from ocean
      color remote sensing.
AB  - Knowledge on absorption by colored dissolved organic matter, a(cdom), spatio
      temporal variability in coastal areas is of fundamental importance in many field
      of researches related to biogeochemical cycles studies, coastal areas management,
      as well as land and water interactions in the coastal domain. A new method, based
      on the theoretical link between the vertical attenuation coefficient, K(d), and
      the absorption coefficient, has been developed to assess a(cdom). This method,
      confirmed from radiative transfer simulations and in situ measurements, and
      tested on an independent in situ data set (N = 126), allows a(cdom) to be
      assessed with a Mean Relative Absolute Difference, MRAD, of 33% over two order of
      magnitude (from 0.01 to 1.16 m(-1)). In the frame of ocean color observation,
      K(d) is not directly measured but estimated from the remote sensing reflectance,
      R(rs). Based on 109 satellite (SeaWiFS) and in situ coincident (i.e. match-up)
      data points a(cdom) is retrieved with a MRAD value of 37%. This simple model
      generally presents slightly better performances than recently developed empirical
      or semi-analytical algorithms.

PMID- 24921508
TI  - Tunable microwave generation of a monolithic dual-wavelength distributed feedback
      laser.
AB  - The dynamic behavior of a monolithic dual-wavelength distributed feedback laser
      was fully investigated and mapped. The combination of different driving currents
      for master and slave lasers can generate a wide range of different operational
      modes, from single mode, period 1 to chaos. Both the optical and microwave
      spectrum were recorded and analyzed. The detected single mode signal can
      continuously cover from 15GHz to 50GHz, limited by photodetector bandwidth. The
      measured optical four-wave-mixing pattern indicates that a 70GHz signal can be
      generated by this device. By applying rate equation analysis, the important laser
      parameters can be extracted from the spectrum. The extracted relaxation resonant
      frequency is found to be 8.96GHz. With the full operational map at hand, the
      suitable current combination can be applied to the device for proper
      applications. 

PMID- 24921509
TI  - A large bistable negative lens by integrating a polarization switch with a
      passively anisotropic focusing element.
AB  - A bistable negative lens with a large aperture size (~10mm) by integrating a
      polarization switch of ferroelectric liquid crystals (FLCs) with a passively
      anisotropic focusing element is demonstrated. The proposed lens not only exhibits
      electrically tunable bistability but also fast response time of sub-milliseconds.
      The tunable lens power is from 0 to -1.74 Diopters. The electro-optical
      properties and imaging performances are demonstrated. The impact of this study is
      to provide a solution of electrically bistable liquid crystal lenses for the
      applications of portable devices, wearable devices and colored ophthalmic lenses.

PMID- 24921510
TI  - Mapping the refractive index of optically transparent samples by means of optical
      nanoantenna attached to fiber microaxicon.
AB  - We demonstrate analytically and numerically that the detection of the spectral
      response of a single spherical Au nanoantenna allows one to map very small (down
      to 5.10(-4) RIU) variations of the refractive index of an optically transparent
      sample. Spectral shift of the dipole local plasmon resonance wavelength of the
      nanoantenna and the spectral sensitivity of the method developed was estimated by
      using simple analytical quasi-static model. A pointed scanning probe based on
      fiber microaxicon with the Au spherical nanoantenna attached to its tip was
      proposed to realize the RI mapping method. Finite-difference time-domain
      numerical simulations of the spectral properties of the proposed probe are in
      good agreement with the theoretical quasi-electrostatic estimations for a radius
      of the nanoantenna not exceeding the skin depth of Au.

PMID- 24921511
TI  - Visual space assessment of two all-reflective, freeform, optical see-through head
      worn displays.
AB  - Head-worn displays have begun to infiltrate the commercial electronics scene as
      mobile computing power has decreased in price and increased in availability. A
      prototypical head-worn display is both lightweight and compact, while achieving
      high quality optical performance. In off-axis geometries, freeform optical
      surfaces allow an optical designer additional degrees of freedom necessary to
      create a device that meets these conditions. In this paper, we show two optical
      see-through head-worn display designs, both comprising two freeform elements with
      an emphasis on visual space assessment and parameters. 

PMID- 24921512
TI  - Concurrent optical parametric down-conversion in chi(2) nonlinear photonic
      crystals.
AB  - We experimentally investigated concurrent parametric downconversion processes in
      a two-dimensional hexagonally poled lithium tantalate crystal. The substantial
      enhancement of parametric gain was observed when concurrent processes shared a
      common parametric beam. Both degenerate and nondegenerate concurrent parametric
      downconversion processes were studied. Analyses of the spatial forms and output
      angles showed a strong dependence on the working temperature, during which a well
      defined beamlike parametric output was observed. Our results will stimulate the
      design for coherent high-gain generation of multiple parametric beams and also
      shed light on the compact engineering of path-entanglement with specific spatial
      forms based on concurrent spontaneous parametric downconversion processes. 

PMID- 24921513
TI  - Remote open-path cavity-ringdown spectroscopic sensing of trace gases in air,
      based on distributed passive sensors linked by km-long optical fibers.
AB  - A continuous-wave, rapidly swept cavity-ringdown spectroscopic technique has been
      developed for localized atmospheric sensing of trace gases at remote sites. It
      uses one or more passive open-path optical sensor units, coupled by optical fiber
      over distances of >1 km to a single transmitter/receiver console incorporating a
      photodetector and a swept-frequency diode laser tuned to molecule-specific near
      infrared wavelengths. Ways to avoid interference from stimulated Brillouin
      scattering in long optical fibers have been devised. This rugged open-path
      system, deployable in agricultural, industrial, and natural atmospheric
      environments, is used to monitor ammonia in air. A noise-limited minimum
      detectable mixing ratio of ~11 ppbv is attained for ammonia in nitrogen at
      atmospheric pressure. 

PMID- 24921514
TI  - Phase sensitivity of fundamental mode of hollow-core photonic bandgap fiber to
      internal gas pressure.
AB  - The response of the commercial HC-1550-02 hollow-core photonic bandgap fiber (HC
      PBF) to gas pressure applied internally to the hollow-core was experimentally
      investigated. The transmission spectrum of the HC-PBF was hardly affected by the
      pressure, while the accumulated phase of the fundamental optical mode showed a
      normalized pressure sensitivity of 1.044 * 10(-2) rad/(Pa?m), which is over two
      orders of magnitude higher than that to the external pressure. Numerical
      simulation showed that the observed high sensitivity to pressure is due to the
      pressure-induced refractive index change of air inside the hollow-core. This
      research could find potential applications in high sensitivity static and dynamic
      pressure measurement and optical phase manipulation.

PMID- 24921515
TI  - A simple method for quality evaluation of micro-optical components based on 3D
      IPSF measurement.
AB  - This paper presents a simple method based on the measurement of the 3D intensity
      point spread function for the quality evaluation of high numerical aperture micro
      optical components. The different slices of the focal volume are imaged thanks to
      a microscope objective and a standard camera. Depending on the optical
      architecture, it allows characterizing both transmissive and reflective
      components, for which either the imaging part or the component itself are moved
      along the optical axis, respectively. This method can be used to measure focal
      length, Strehl ratio, resolution and overall wavefront RMS and to estimate
      optical aberrations. The measurement setup and its implementation are detailed
      and its advantages are demonstrated with micro-ball lenses and micro-mirrors.
      This intuitive method is adapted for optimization of micro-optical components
      fabrication processes, especially because heavy equipments and/or data analysis
      are not required. 

PMID- 24921516
TI  - Shaped multi-cycle two-color laser field for generating an intense isolated XUV
      pulse toward 100 attoseconds.
AB  - The isolated attosecond pulse (IAP) generated from high-order harmonic (HH)
      radiation has been established as an important technique for the ultrafast optics
      over past decade. The applications of IAP in ultrafast processes can be greatly
      extended by further developing the high-intensity IAP. Here, we theoretically
      propose to shape a two-color field by performing peak amplitude-wavelength
      analysis. It is found that a 240-as IAP can be generated even without carrier
      envelop phase (CEP) stabilization using a 25 fs/800 nm fundamental field and a
      relative weak 25 fs/1330 nm control field, which enables us to markedly relax the
      requirements of the driving laser fields both in pulse duration and CEP control.
      On the other hand, if the CEPs of driving laser fields are stabilized, a 65-eV
      broadband continual harmonic, supporting a 81-as IAP, can be directly produced
      with the optimized intensity ratio of 0.866 and control wavelength of 1400 nm.
      Moreover, the propagation effect of two-color field on the macroscopic build-up
      of HH for generating a high-energy IAP is discussed. We found that the method of
      phase match still works for the efficient continuous harmonic generation as long
      as the ionization level and the pressure of gas medium are kept low enough. Since
      the phase-matched short IAP can be generated with our shaped two-color scheme in
      combination with a relaxed requirement of driving laser fields, the commercial
      available high-energy laser source with a loosely focused geometry is promising
      for scaling up the energy of IAP, showing the potential for the realization of
      IAP with high focused intensity toward 100 attoseconds. 

PMID- 24921517
TI  - Electron-beam lithography of plasmonic nanorod arrays for multilayered optical
      storage.
AB  - In this paper we demonstrate multilayer fabrication of plasmonic gold nanorod
      arrays using electron-beam lithography (EBL), and show that this structure could
      be used for multilayered optical storage media capable of continuous-wave (cw)
      laser readout. The gold nanorods fabricated using the EBL method are aligned
      perfectly and homogeneous in size and shape, allowing the polarization response
      of surface plasmon resonance (SPR) to be observed through ensemble array. This
      property in turn permits polarization detuned SPR readout possible and other
      manipulations such as progressively twisted arrays through the multilayers to
      make cw readout possible through deeper layers without too much extinction loss.
      The layered gold nanorod arrays are separated by thick spacer layer to enable the
      optical resolving of individual layers. Using this method, we demonstrated four
      fold reduction in extinction loss for cw readout in three-layer structure. The
      current technique of multilayer fabrication and readout can be useful in 3
      dimensional fabrication of plasmonic circuits and structures. 

PMID- 24921518
TI  - Sub-130 fs mode-locked Er-doped fiber laser based on topological insulator.
AB  - In this work we present for the first time, to the best of our knowledge, a
      stretched-pulse mode-locked fiber laser based on topological insulator. As a
      saturable absorber (SA) a ~0.5 mm thick lump of antimony telluride (Sb2Te3)
      deposited on a side-polished fiber was used. Such a SA introduced 6% modulation
      depth with 43% of non-saturable losses, which is sufficient for supporting
      stretched-pulse mode-locking. The ring laser resonator based on Er-doped active
      fiber with managed intracavity dispersion was capable of generating ultrashort
      optical pulses with full width at half maximum (FWHM) of 30 nm centered at 1565
      nm. The pulses with duration of 128 fs were repeated with a frequency of 22.32
      MHz.

PMID- 24921519
TI  - Coherent Fourier scatterometry for detection of nanometer-sized particles on a
      planar substrate surface.
AB  - Inspection tools for nano-particle contamination on a planar substrate surface is
      a critical problem in micro-electronics. The present solutions are either
      expensive and slow or inexpensive and fast but have low sensitivity because of
      limitations due to diffraction. Most of them are also substrate specific. In this
      article we report how Coherent Fourier Scatterometry is used for detection of
      particles smaller than lambda/4. Merits of the technique, especially, the
      procedures to improve SNR, its flexibility and its robustness on rough surfaces
      are discussed with simulated and experimental results. 

PMID- 24921520
TI  - Radiation pattern of plasmonic nano-antennas in a homogeneous medium.
AB  - Radiation patterns from plasmonic nano-antennas formed on a glass substrate were
      investigated using index-matching oils. It was confirmed that the pattern from
      single nano-antennas for various cases of index-mismatching between the substrate
      and the oil is explained well by the patterns of infinitesimal electric dipoles.
      We found that for an angular resolution of 2 degrees , the index mismatch must be
      smaller than 0.001 to realize isotropic radiation. By using the appropriate
      condition, the radiation patterns of nano Yagi-Uda antennas in a quasi
      homogeneous medium were obtained experimentally. 

PMID- 24921521
TI  - A superradiant clock laser on a magic wavelength optical lattice.
AB  - An ideal superradiant laser on an optical clock transition of noninteracting cold
      atoms is predicted to exhibit an extreme frequency stability and accuracy far
      below mHz-linewidth. In any concrete setup sufficiently many atoms have to be
      confined and pumped within a finite cavity mode volume. Using a magic wavelength
      lattice minimizes light shifts and allows for almost uniform coupling to the
      cavity mode. Nevertheless, the atoms are subject to dipole-dipole interaction and
      collective spontaneous decay which compromises the ultimate frequency stability.
      In the high density limit the Dicke superradiant linewidth enhancement will
      broaden the laser line and nearest neighbor couplings will induce shifts and
      fluctuations of the laser frequency. We estimate the magnitude and scaling of
      these effects by direct numerical simulations of few atom systems for different
      geometries and densities. For Strontium in a regularly filled magic wavelength
      configuration atomic interactions induce small laser frequency shifts only and
      collective spontaneous emission weakly broadens the laser. These interactions
      generally enhance the laser sensitivity to cavity length fluctuations but for
      optimally chosen operating conditions can lead to an improved synchronization of
      the atomic dipoles. 

PMID- 24921522
TI  - Pulse compression and broadening by reflection from a moving front of a photonic
      crystal.
AB  - Previously, the effect of pulse bandwidth compression or broadening was observed
      in reflection from a moving front together with the Doppler shift. In this
      letter, an approach is presented, which alters pulse bandwidth without change in
      the central frequency. It occurs when light is reflected from a moving front of
      an otherwise stationary photonic crystal. This means that the photonic crystal
      lattice as such is stationary and only its boundary to the environment is moving,
      thus extruding (or shortening) the photonic crystal medium. The compression
      (broadening) factor depends on the front velocity and is the same as for the
      conventional Doppler shift. Complete reflection and transformation of the pulse
      can be achieved even with weak refractive index contrast, what makes the approach
      experimentally viable. 

PMID- 24921523
TI  - Manipulating coherence resonance in a quantum dot semiconductor laser via
      electrical pumping.
AB  - Excitability and coherence resonance are studied in a semiconductor quantum dot
      laser under short optical self-feedback. For low pump levels, these are observed
      close to a homoclinic bifurcation, which is in correspondence with earlier
      observations in quantum well lasers. However, for high pump levels, we find
      excitability close to a boundary crisis of a chaotic attractor. We demonstrate
      that in contrast to the homoclinic bifurcation the crisis and thus the excitable
      regime is highly sensitive to the pump current. The excitability threshold
      increases with the pump current, which permits to adjust the sensitivity of the
      excitable unit to noise as well as to shift the optimal noise strength, at which
      maximum coherence is observed. The shift adds up to more than one order of
      magnitude, which strongly facilitates experimental realizations. 

PMID- 24921524
TI  - On the absorption and electromagnetic field spectral shifts in plasmonic
      nanotriangle arrays.
AB  - The behavior of the electromagnetic field interaction with gold nanotriangles
      organized in bow-tie arrays is investigated. A side-by-side comparison between
      the measured absorbance of the array and the modelled integrated electric field
      resonances confined around the gold structures is presented and discussed to
      explain the spectral shift between both parameters. Finite difference time domain
      calculations and Raman measurements of gold triangles of different sizes and
      periodicity are systematically performed. Numerical calculations show that the
      spectral maximum of the electric field varies in distinct areas over the metallic
      structures. 

PMID- 24921525
TI  - Low-loss plasmon-triggered switching between reflected free-space diffraction
      orders.
AB  - Surface plasmon coupling of a TM polarized free space incident beam by means of
      the + 1st or the -2nd order of a smooth corrugation grating at a metal surface
      causes the cancellation of the diffracted -1st order free space beam and a
      maximum of the 0th order Fresnel reflection whereas the converse occurs midway
      between these two conditions. This implies that angular tilting of the element or
      wavelength scanning provokes the switching between the -1st and 0th reflected
      orders. This plasmon-mediated effect on propagating free-space beams exhibits
      remarkably low absorption losses. 

PMID- 24921526
TI  - Fabrication and characterization of a hybrid four-hole AsSe2-As2S5
      microstructured optical fiber with a large refractive index difference.
AB  - A hybrid four-hole AsSe2-As2S5 microstructured optical fiber (MOF) with a large
      refractive index difference is fabricated by the rod-in-tube drawing technique.
      The core and the cladding are made from the AsSe2 glass and As2S5 glass,
      respectively. The propagation loss is ~1.8 dB/m and the nonlinear coefficient is
      ~2.03 * 10(4) km(-1)W(-1) at 2000 nm. Raman scattering is observed in the normal
      dispersion regime when the fiber is pumped by a 2 MUm mode-locked picosecond
      fiber laser. Additionally, soliton is generated in the anomalous dispersion
      regime when the fiber is pumped by an optical parametric oscillator (OPO) at the
      pump wavelength of ~3000 nm.

PMID- 24921527
TI  - Diffuse imaging and radius dependent frequency correlations in strongly
      scattering media.
AB  - A new probe of multiple scattering material is demonstrated experimentally. Light
      from a tunable wavelength source is focused to a point on the surface of an
      opaque slab. A fraction of this light penetrates into the slab, is multiply
      scattered, and reemerges at the surface creating a surface speckle pattern. The
      full spatial and frequency speckle can be easily and quickly recorded using a CCD
      and an acoustooptical tunable filter. Both the average intensity and frequency
      correlations of intensity are analyzed as a function of the distance to the
      source. This method is demonstrated experimentally for white paint. The resulting
      model yields information about both the static and dynamic transport properties
      of the sample. The technique has prospects for both static and time resolved
      diffuse imaging in strongly scattering materials. The setup can be easily used as
      an add-on to a standard bright field microscope. 

PMID- 24921528
TI  - Wave-optical design of a combined refractive-diffractive varifocal lens.
AB  - A novel type of integrated refractive-diffractive varifocal membrane lens is
      designed and analyzed by wave-optical methods. In contrast to other hybrid
      devices, the diffractive microstructure is directly imprinted onto the soft
      deflecting membrane, allowing for a high level of integration. Elastic
      deformation is taken into account by mechanical simulations with the finite
      element method (FEM). We show, that the superimposed structure can considerably
      suppress chromatic and spherical aberration. Furthermore, our algorithm is
      successfully applied to design a confocal hyperspectral lens. 

PMID- 24921529
TI  - Stimulated Brillouin scattering of pulses in optical fibers.
AB  - We derive analytic expressions for the Brillouin thresholds of square pulses in
      optical fibers. The equations are valid for pulse durations in the transient
      Brillouin scattering regime (less than 100 nsec), as well for longer pulses, and
      have been confirmed experimentally. Our analysis also gives a firm theoretical
      prediction that the Brillouin gain width increases dramatically for intense
      pulses, from tens of MHz to one GHz or more. 

PMID- 24921530
TI  - Generation of mode-locked optical pulses at 1035 nm from a fiber Bragg grating
      stabilized semiconductor laser diode.
AB  - We report the generation of transform-limited, ~18 ps optical pulses from a fiber
      Bragg grating (FBG) stabilized semiconductor laser diode. Up to 7.2 pJ of pulse
      energy and a peak power of 400mW were achieved when operating at a repetition
      frequency of 832.6 MHz, a multiple of the cavity (diode + FBG) free spectral
      range (FSR). A small detuning in the repetition frequency resulted in broader
      optical pulses. We have shown experimentally the transition from a gain-switched
      regime of operation to mode-locked operation once the injection current
      modulation frequency is set to match a harmonic of the cavity FSR. The transition
      also results in a reduction in the timing jitter of the optical pulses. 

PMID- 24921531
TI  - Spatial properties of twin-beam correlations at low- to high-intensity
      transition.
AB  - It is shown that spatial correlation functions measured for correlated photon
      pairs at the single-photon level correspond to speckle patterns visible at high
      intensities. This correspondence is observed for the first time in one
      experimental setup by using different acquisition modes of an intensified CCD
      camera in low and high intensity regimes. The behavior of intensity auto- and
      cross-correlation functions in dependence on pump-beam parameters including power
      and transverse profile is investigated. 

PMID- 24921532
TI  - Ring artifact correction using detector line-ratios in computed tomography.
AB  - Ring artifacts in computed tomography (CT) images degrade image quality and
      obscure the true shapes of objects. While several correction methods have been
      developed, their performances are often task-dependent and not generally
      applicable. Here, we propose a novel method to reduce ring artifacts by
      calculating the ratio of adjacent detector elements in the projection data,
      termed the line-ratio. Our method estimates the sensitivity of each detector
      element and equalizes them in sinogram space. As a result, the stripe pattern can
      be effectively removed from sinogram data, thereby also removing ring artifacts
      from the reconstructed CT image. Numerical simulations were performed to evaluate
      and compare the performance of our method with that of conventional methods. We
      also tested our method experimentally and demonstrated that our method has
      superior performance to other methods. 

PMID- 24921533
TI  - Hybrid exposure for depth imaging of a time-of-flight depth sensor.
AB  - A time-of-flight (ToF) depth sensor produces noisy range data due to scene
      properties such as surface materials and reflectivity. Sensor measurement
      frequently includes either a saturated or severely noisy depth and effective
      depth accuracy is far below its ideal specification. In this paper, we propose a
      hybrid exposure technique for depth imaging in a ToF sensor so to improve the
      depth quality. Our method automatically determines an optimal depth for each
      pixel using two exposure conditions. To show that our algorithm is effective, we
      compare the proposed algorithm with two conventional methods in qualitative and
      quantitative manners showing the superior performance of proposed algorithm. 

PMID- 24921534
TI  - Tunable ultrathin mantle cloak via varactor-diode-loaded metasurface.
AB  - We propose a tunable strategy for the ultrathin mantle cloak via metasurface. The
      tunable cloak is implemented by loading varactor diodes between two neighboring
      horizontal metallic strips which constitute the metasurface. We demonstrate that
      the varactor diodes enable the capacitive reactance of the metasurface to be
      tunable from -157 Omega to -3 Omega when the DC bias voltage is properly changed.
      The active metasurface is then explored to cloak conformally a conducting
      cylinder. Both numerical and experiment results show that the cloaking frequency
      can be continuously controlled from 2.3 GHz to 3.7 GHz by appropriately adjusting
      the bias voltage. The flexible tunability and good cloaking performance are
      further examined by the measured field distributions. The advanced features of
      tunability, low profile, and conformal ability of the ultrathin cloak pave the
      way for practical applications of cloaking devices. 

PMID- 24921535
TI  - Super-transmission from a finite subwavelength arrangement of slits in a metal
      film.
AB  - A theory is presented for the transmission of transverse magnetic waves through a
      finite number of subwavelength slits in metal film. While a single slit achieves
      the single channel limit on resonance, multiple slits show super-transmission
      exceeding the single channel limit. The phenomenon of super-transmission is
      revealed as a result of cross-coupling of modes and confirmed by simulations. The
      influence of finite permittivity in the IR and microwave regime is included by
      perturbative corrections to the theory. The theory agrees quantitatively with
      past experiments and finite-difference time-domain simulations. By considering
      two or more modes in the slit region, our theory provides an approach to the
      analysis of cross-coupling among slits, which allows for super-transmission and
      features of a Fano resonance. 

PMID- 24921536
TI  - Simulation study on light propagation in an anisotropic turbulence field of
      entrainment zone.
AB  - The convective atmospheric boundary layer was modeled in the water tank. In the
      entrainment zone (EZ), which is at the top of the convective boundary layer
      (CBL), the turbulence is anisotropic. An anisotropy coefficient was introduced in
      the presented anisotropic turbulence model. A laser beam was set to horizontally
      go through the EZ modeled in the water tank. The image of two-dimensional (2D)
      light intensity fluctuation was formed on the receiving plate perpendicular to
      the light path and was recorded by the CCD. The spatial spectra of both
      horizontal and vertical light intensity fluctuations were analyzed. Results
      indicate that the light intensity fluctuation in the EZ exhibits strong
      anisotropic characteristics. Numerical simulation shows there is a linear
      relationship between the anisotropy coefficients and the ratio of horizontal to
      vertical fluctuation spectra peak wavelength. By using the measured temperature
      fluctuations along the light path at different heights, together with the
      relationship between temperature and refractive index, the one-dimensional (1D)
      refractive index fluctuation spectra were derived. The anisotropy coefficients
      were estimated from the 2D light intensity fluctuation spectra modeled by the
      water tank. Then the turbulence parameters can be obtained using the 1D
      refractive index fluctuation spectra and the corresponding anisotropy
      coefficients. These parameters were used in numerical simulation of light
      propagation. The results of numerical simulations show this approach can
      reproduce the anisotropic features of light intensity fluctuations in the EZ
      modeled by the water tank experiment. 

PMID- 24921537
TI  - Third-order optical nonlinearity at 800 and 1300 nm in bismuthate glasses doped
      with silver nanoparticles.
AB  - Large and ultrafast third-order optical nonlinearities in Ag-doped bismuthate
      glasses which are prepared by incorporating Ag ions into bismuthate glasses to
      form Ag nanoparticles through a consecutive melting-quenching-annealing technique
      are reported. Due to the high refractive index of bismuthate glass, surface
      plasmon resonance (SPR) of Ag nanoparticles is extendable to 1400 nm, resulting
      in a higher nonlinear refractive index than bismuthate glass. Femtosecond Z-scans
      show that the nonlinear refractive index, as high as 9.4 * 10(-17) and 5.6 * 10(
      18) m(2) W(-1) at 800 and 1300 nm, respectively, can be achieved by selecting an
      optimized concentration of Ag nano-sized particles. And two-photon absorption at
      800 nm is suppressed due to a blue shift in the band-gap of Ag-doped bismuthate
      glasses, as compared to pristine bismuthate glasses. Optical Kerr shutter
      technique reveals that these nonlinearities have a relaxation time of < 1 ps.

PMID- 24921538
TI  - Design, production and reverse engineering of ultra-steep hot mirrors.
AB  - We present the whole design-production chain of an ultra-steep hot mirror
      produced using the indirect monochromatic monitoring technique. The hot mirror
      without thin layers is designed utilizing the stochastic optimization procedure
      that takes in account upper and lower constraints for layer optical thickness. We
      produced the hot mirror with the ion-assisted electron beam deposition technique
      using indirect monochromatic monitoring strategy, performed reverse engineering
      of the deposited coatings, and illustrated that the random variation of the
      tooling factors in low-index layers is the main factor causing production errors.
      We modified the monitoring strategy with low-index layers monitored by quartz
      crystal monitor, and demonstrated the excellent correspondence to the theoretical
      spectral performance. 

PMID- 24921539
TI  - Digital coherent superposition of optical OFDM subcarrier pairs with Hermitian
      symmetry for phase noise mitigation.
AB  - Digital coherent superposition (DCS) provides an approach to combat fiber
      nonlinearities by trading off the spectrum efficiency. In analogy, we extend the
      concept of DCS to the optical OFDM subcarrier pairs with Hermitian symmetry to
      combat the linear and nonlinear phase noise. At the transmitter, we simply use a
      real-valued OFDM signal to drive a Mach-Zehnder (MZ) intensity modulator biased
      at the null point and the so-generated OFDM signal is Hermitian in the frequency
      domain. At receiver, after the conventional OFDM signal processing, we conduct
      DCS of the optical OFDM subcarrier pairs, which requires only conjugation and
      summation. We show that the inter-carrier-interference (ICI) due to phase noise
      can be reduced because of the Hermitain symmetry. In a simulation, this method
      improves the tolerance to the laser phase noise. In a nonlinear WDM transmission
      experiment, this method also achieves better performance under the influence of
      cross phase modulation (XPM). 

PMID- 24921540
TI  - Design a light pattern of multiple concentric circles for LED fishing lamps using
      Fourier series and an energy mapping method.
AB  - Fourier series and an energy mapping method were used in this study to design a
      lens that produces a light pattern of multiple concentric circles (LPMCC) for a
      light-emitting diode (LED) fishing lamp. Fourier series were used to represent
      the light intensity distribution curve (LIDC) of the LPMCC light pattern. Energy
      mapping involves performing angular energy mapping based on the LIDCs of an LED
      light source and LPMCC to design a freeform lens. Type I and Type II LPMCC lenses
      were designed according to the phototaxis behavior of fish to create a LPMCC
      light pattern of interleaving light-dark zones that attracts fish shoals to stay
      in an area for a long period. The experimental results indicated that, in
      comparing the LIDCs of the Type I and II lenses with the respective simulation
      values, the normalized cross-correlation (NCC) value reached 96%. According to a
      24-hour observation of the phototaxis of Poecilia reticulata to evaluate the
      effectiveness of the proposed light pattern to attract fish, when a fish shoal
      was habituated to a light source that emitted constant illumination light, it
      gradually moved away from the intense light zone and hovered around the junction
      of the light and dark zones. In the future, the design used in this study can be
      applied to LED fishing lamps to replace traditional fishing lamps. 

PMID- 24921541
TI  - Rapid quantitative phase imaging for partially coherent light microscopy.
AB  - Partially coherent light provides promising advantages for imaging applications.
      In contrast to its completely coherent counterpart, it prevents image degradation
      due to speckle noise and decreases cross-talk among the imaged objects. These
      facts make attractive the partially coherent illumination for accurate
      quantitative imaging in microscopy. In this work, we present a non
      interferometric technique and system for quantitative phase imaging with
      simultaneous determination of the spatial coherence properties of the sample
      illumination. Its performance is experimentally demonstrated in several examples
      underlining the benefits of partial coherence for practical imagining
      applications. The programmable optical setup comprises an electrically tunable
      lens and sCMOS camera that allows for high-speed measurement in the millisecond
      range. 

PMID- 24921542
TI  - A 3D integral imaging optical see-through head-mounted display.
AB  - An optical see-through head-mounted display (OST-HMD), which enables optical
      superposition of digital information onto the direct view of the physical world
      and maintains see-through vision to the real world, is a vital component in an
      augmented reality (AR) system. A key limitation of the state-of-the-art OST-HMD
      technology is the well-known accommodation-convergence mismatch problem caused by
      the fact that the image source in most of the existing AR displays is a 2D flat
      surface located at a fixed distance from the eye. In this paper, we present an
      innovative approach to OST-HMD designs by combining the recent advancement of
      freeform optical technology and microscopic integral imaging (micro-InI) method.
      A micro-InI unit creates a 3D image source for HMD viewing optics, instead of a
      typical 2D display surface, by reconstructing a miniature 3D scene from a large
      number of perspective images of the scene. By taking advantage of the emerging
      freeform optical technology, our approach will result in compact, lightweight,
      goggle-style AR display that is potentially less vulnerable to the accommodation
      convergence discrepancy problem and visual fatigue. A proof-of-concept prototype
      system is demonstrated, which offers a goggle-like compact form factor, non
      obstructive see-through field of view, and true 3D virtual display. 

PMID- 24921543
TI  - Projection screen reflectance control for high contrast display using
      photochromic compounds and UV LEDs.
AB  - This paper presents the first proof-of-concept implementation and the principle
      that realizes a projection display whose contrast does not decrease even with
      existing inter-reflection of projection light or environmental light. We propose
      the use of photochromic compounds (PhC) to control reflectance of a projection
      surface. PhC changes color chemically when exposed to UV light. A PhC is applied
      to a surface to control its reflectance by radiating UV light from a UV-LED
      array. An image is projected from a visible projector onto the surface to boost
      the contrast. The proof-of-concept experiment shows that the prototype system
      achieves approximately three times higher contrast than a projection-only system
      under natural light. 

PMID- 24921544
TI  - Generalized full-vector multi-mode matching analysis of whispering gallery
      microcavities.
AB  - We outline a full-vectorial three-dimensional multi-mode matching technique in a
      cylindrical coordinate system that addresses the mutual coupling among multiple
      modes co-propagating in a perturbed whispering gallery mode microcavity. In
      addition to its superior accuracy in respect to our previously implemented single
      mode matching technique, this current technique is suitable for modelling
      waveguide-to-cavity coupling where the influence of multi-mode coupling is non
      negligible. Using this methodology, a robust scheme for hybrid integration of a
      microcavity onto a silicon-on-insulator platform is proposed. 

PMID- 24921545
TI  - Adaptive millimeter-wave synthetic aperture imaging for compressive sampling of
      sparse scenes.
AB  - We apply adaptive sensing techniques to the problem of locating sparse metallic
      scatterers using high-resolution, frequency modulated continuous wave W-band
      RADAR. Using a single detector, a frequency stepped source, and a lateral
      translation stage, inverse synthetic aperture RADAR reconstruction techniques are
      used to search for one or two wire scatterers within a specified range, while an
      adaptive algorithm determined successive sampling locations. The two-dimensional
      location of each scatterer is thereby identified with sub-wavelength accuracy in
      as few as 1/4 the number of lateral steps required for a simple raster scan. The
      implications of applying this approach to more complex scattering geometries are
      explored in light of the various assumptions made. 

PMID- 24921546
TI  - Image matching technology in high power LED's eutectic welding.
AB  - As the integration packaging density of high-power LED (Light Emitting Diode)
      chip modules become higher and higher, the accuracy and speed of visual
      inspection require higher demands correspondingly. The accurate position matching
      of substrates and flip-chip LEDs is one of the key technologies in the automatic
      eutectic welding process. In this paper we propose a method based on image
      features to complete the matching of the substrates and the flip-chip LEDs.
      Firstly, the substrate images and the flip-chip images are pre-processed
      respectively to obtain binary images. Then we apply Hough transformation to
      detect straight lines on the binary images, and find out the main linear
      directions to trigger the mechanical arms to adjust the positions of the
      substrate and the chip initially. Thirdly, we use eight neighbors interconnected
      domain algorithm for the first time to locate notable features of the substrate,
      and pass the located information to the control system to trigger the mechanical
      arm to adjust the substrate for the second time. At the same time, projection
      algorithm is applied to locate the anode of the flip-chip to drive the mechanical
      arm to adjust the position of the flip-chip again. Finally, the position
      information is used to trigger the mechanical arm to accomplish the matching of
      the substrate and the flip-chip. The proposed method improves the speed of
      matching on the basis of the accuracy of matching, which achieves these
      requirements of real-time and high accuracy applications. 

PMID- 24921547
TI  - Dynamic cosine-Gauss plasmonic beam through phase control.
AB  - We carry out an approach to dynamic manipulation of a nondiffracting cosine-Gauss
      plasmonic beam (CGPB) illuminated with an incident phase modulation within
      nanostructures by a spatial light modulator (SLM). By changing the hologram
      addressed on the SLM, dynamic control on the lobe width and the propagating
      direction of the CGPB is experimentally verified. Finally, we demonstrate an
      application example of this dynamic CGPB in routing optical signals to
      multichannel subwavelength wave guides through numerical simulation. 

PMID- 24921548
TI  - Low-scattering surface plasmon refraction with isotropic materials.
AB  - We show theoretically and numerically that a planar structure consisting of two
      isotropic dielectric layers can be used to minimize parasitic scattering of
      surface plasmon polaritons for arbitrary incidence angle. The average scattering
      losses are reduced by an order-of-magnitude down to 1-3%. The surface plasmon
      refraction with the scattering suppression can be accurately described by an
      analytical model based on the Fresnel equations. The proposed approach can be
      used for the design of plasmonic lenses, reflectors, plasmonic crystals and
      plasmonic laser cavities. 

PMID- 24921549
TI  - Waveguide-integrated single-crystalline GaP resonators on diamond.
AB  - Large-scale entanglement of nitrogen-vacancy (NV) centers in diamond will require
      integration of NV centers with optical networks. Toward this goal, we present the
      fabrication of single-crystalline gallium phosphide (GaP) resonator-waveguide
      coupled structures on diamond. We demonstrate coupling between 1 MUm diameter GaP
      disk resonators and waveguides with a loaded Q factor of 3,800, and evaluate
      their potential for efficient photon collection if integrated with single photon
      emitters. This work opens a path toward scalable NV entanglement in the hybrid
      GaP/diamond platform, with the potential to integrate on-chip photon collection,
      switching, and detection for applications in quantum information processing. 

PMID- 24921551
TI  - 210 W single-frequency, single-polarization, thulium-doped all-fiber MOPA.
AB  - A high-power single-frequency, single-polarization, thulium-doped all-fiber
      master-oscillator power-amplifier (MOPA) is demonstrated by using all
      polarization-maintaining (all-PM) thulium-doped fiber and all-PM-fiber
      components. The MOPA yielded 210 W of single-frequency, linear-polarized laser
      output at central wavelength of 2000.9 nm with a polarization extinction ratio
      (PER) of >17 dB. No indication of stimulated Brillouin scattering (SBS) could be
      observed at the highest output power level, and the output power was only
      currently limited by available pump power. To the best of our knowledge, this is
      the first demonstration of average output power exceeding 200 W from a single
      frequency, single-polarization, thulium-doped all-fiber laser at 2 um wavelength
      region. 

PMID- 24921550
TI  - Novel ultra-broadband polarization splitter-rotator based on mode-evolution
      tapers and a mode-sorting asymmetric Y-junction.
AB  - A novel silicon-on-insulator (SOI) polarization splitter-rotator is proposed
      based on mode-evolution tapers and a mode-sorting asymmetric Y-junction. The
      tapers are designed to adiabatically convert the input TM0 mode into the TE1
      mode, which will evolve into the TE0 mode in the wide output arm while the input
      TE0 mode excites the TE0 mode in the narrow arm. The numerical simulation results
      show that the mode conversion efficiency increases with the lengths of the tapers
      and the Y-junction for the output waveguide widths in a large range. This
      proposed device has < 0.4 dB insertion loss with > 12 dB extinction ratio in an
      ultra-broad wavelength range from 1350 nm to 1750 nm. With such a broad operating
      bandwidth, this device offers potential applications for polarization diversity
      operating across every communication bands. Fabrication tolerance analysis is
      also performed in terms of the device width variation, the slab height variation
      and the variation of the upper-cladding refractive index.

PMID- 24921552
TI  - Optical serial coherent analyzer of radio-frequency (OSCAR).
AB  - Optical serial coherent analyzer of radio-frequency is a novel scheme that
      enables fast-scanning microwave signal measurements in a large bandwidth. The
      measurements are performed based on serial channelization realized by using a
      fast scanning laser source as the local oscillator to down-convert the to-be
      measured radio-frequency (RF) signals. Optical coherent detection effectively
      removes interferences induced by RF's self-beating and guarantees the accuracy of
      measurements. In the experimental demonstration, instantaneous multi-frequency
      measurements and vector information acquisition of RF signals can be achieved by
      this scheme within 2.8 MUs over 14 GHz bandwidth. 

PMID- 24921553
TI  - Aperture-scanning Fourier ptychography for 3D refocusing and super-resolution
      macroscopic imaging.
AB  - We report an imaging scheme, termed aperture-scanning Fourier ptychography, for
      3D refocusing and super-resolution macroscopic imaging. The reported scheme scans
      an aperture at the Fourier plane of an optical system and acquires the
      corresponding intensity images of the object. The acquired images are then
      synthesized in the frequency domain to recover a high-resolution complex sample
      wavefront; no phase information is needed in the recovery process. We demonstrate
      two applications of the reported scheme. In the first example, we use an aperture
      scanning Fourier ptychography platform to recover the complex hologram of
      extended objects. The recovered hologram is then digitally propagated into
      different planes along the optical axis to examine the 3D structure of the
      object. We also demonstrate a reconstruction resolution better than the detector
      pixel limit (i.e., pixel super-resolution). In the second example, we develop a
      camera-scanning Fourier ptychography platform for super-resolution macroscopic
      imaging. By simply scanning the camera over different positions, we bypass the
      diffraction limit of the photographic lens and recover a super-resolution image
      of an object placed at the far field. This platform's maximum achievable
      resolution is ultimately determined by the camera's traveling range, not the
      aperture size of the lens. The FP scheme reported in this work may find
      applications in 3D object tracking, synthetic aperture imaging, remote sensing,
      and optical/electron/X-ray microscopy. 

PMID- 24921554
TI  - Cascaded all-optical operations in a hybrid integrated 80-Gb/s logic circuit.
AB  - We demonstrate logic functionalities in a high-speed all-optical logic circuit
      based on differential Mach-Zehnder interferometers with semiconductor optical
      amplifiers as the nonlinear optical elements. The circuit, implemented by hybrid
      integration of the semiconductor optical amplifiers on a planar lightwave circuit
      platform fabricated in silica glass, can be flexibly configured to realize a
      variety of Boolean logic gates. We present both simulations and experimental
      demonstrations of cascaded all-optical operations for 80-Gb/s on-off keyed data. 

PMID- 24921555
TI  - Modified E91 protocol demonstration with hybrid entanglement photon source.
AB  - We report on an experimental demonstration of the modified Ekert 91 protocol of
      quantum key distribution using a hybrid entanglement source with two different
      degrees of freedoms, a 1550 nm time-bin qubit and 810 nm polarization qubit. The
      violation of the Clauser-Horne-Shimony-Holt inequality could be demonstrated for
      the entanglement between the polarization qubit in free space and the time-bin
      qubit through 20 km fiber transmission. The secure key rate in our system is
      estimated 70-150 bps. 

PMID- 24921556
TI  - Picosecond supercontinuum light source for stroboscopic white-light
      interferometry with freely adjustable pulse repetition rate.
AB  - We present a picosecond supercontinuum light source designed for stroboscopic
      white-light interferometry. This source offers a potential for high-resolution
      characterization of vibrational fields in electromechanical components with
      frequencies up to the GHz range. The light source concept combines a gain
      switched laser diode, the output of which is amplified in a two-stage fiber
      amplifier, with supercontinuum generation in a microstructured optical fiber.
      Implemented in our white-light interferometer setup, optical pulses with
      optimized spectral properties and below 310 ps duration are used for stroboscopic
      illumination at freely adjustable repetition rates. The performance of the source
      is demonstrated by characterizing the surface vibration field of a square-plate
      silicon MEMS resonator at 3.37 MHz. A minimum detectable vibration amplitude of
      less than 100 pm is reached. 

PMID- 24921557
TI  - Optoelectronic oscillator for a measurement of acoustic velocity in acousto-optic
      device.
AB  - We report a novel means of measuring the acoustic velocity based on a well-known
      acousto-optic interaction. With an acousto-optic modulator (AOM), we construct an
      optoelectronic oscillator (OEO) that can measure the acoustic velocity in the AOM
      directly. The free spectral range between the modes is a function of the total
      loop length of the OEO, which is mainly dependent on the propagation time of the
      acoustic wave through the AOM. By changing the propagation time, we measured the
      acoustic velocity from the variation of the free spectral range. The results are
      reported and compared with earlier results. This method is insensitive to the
      variation of the optical phase shift. In addition, the high frequency-stability
      and microwave spectral purity of the OEO allow reliable and precise measurements.

PMID- 24921558
TI  - Application of global phase filtering method in multi frequency measurement.
AB  - In reverse engineering, reconstruction of 3D point cloud data is the key step to
      acquire the final profile of the object. However, the quality of 3D
      reconstruction is influenced by noise in the three-dimensional measurement. This
      paper aims to tackle the issue of removing the noisy data from the complex point
      cloud data. The 3D-GPF (Three Dimensional Global Phase Filtering) global phase
      filtering method is proposed based on the study of phase filtering method,
      consisting of the steps below. Firstly, the six-step phase shift profilometry is
      used to obtain the local phase information, and encoding the obtained phase
      information. Through the global phase unwrapping method, the global phase can be
      acquired. Secondly, 3D-GPF method is used for the obtained global phase. Finally,
      the effect of 3D reconstruction is analyzed after the global phase filtering.
      Experimental results indicate that the noisy points of three-dimensional graphics
      is reduced 98.02%, the speed of 3D reconstruction is raised 12%.The effect of the
      proposed global phase filtering method is better than DCT and GSM methods. It is
      high precision and fast speed, and can be widely used in other 3D reconstruction
      application. 

PMID- 24921559
TI  - All solid-state 191.7 nm deep-UV light source by seventh harmonic generation of
      an 888 nm pumped, Q-switched 1342 nm Nd:YVO4 laser with excellent beam quality.
AB  - In this paper we report on the realization of a deep-UV light source using the
      1.3 MUm transition of neodymium as pumping wavelength. The 191.7 nm radiation was
      obtained by generating the seventh harmonic of a high-power Q-switched 1342 nm
      Nd:YVO4 laser. A cesium lithium borate crystal was used for sum frequency mixing
      of the sixth harmonic and the fundamental. With a total of four conversion
      stages, up to 240 mW were achieved, with excellent beam quality at 155 mW (M2 <
      1.7) and 190 mW (M2 < 1.9).

PMID- 24921560
TI  - Solution for pseudoscopic problem in integral imaging using phase-conjugated
      reconstruction of lens-array holographic optical elements.
AB  - We propose an optical pseudoscopic to orthoscopic conversion method for integral
      imaging using a lens-array holographic optical element (LAHOE), which solves the
      pseudoscopic problem. The LAHOE reconstructs an array of diverging spherical
      waves when a probe wave with the phase-conjugated condition is imposed on it,
      while an array of converging spherical waves is reconstructed in ordinary
      reconstruction. For given pseudoscopic elemental images, the array of the
      diverging spherical waves integrates the orthoscopic three-dimensional images
      without a distortion. The principle of the proposed method is verified by the
      experiments of displaying the integral imaging on the LAHOE using computer
      generated and optically acquired elemental images. 

PMID- 24921561
TI  - Quantum theory of a spaser-based nanolaser.
AB  - We present a quantum theory of a spaser-based nanolaser, under the bad-cavity
      approximation. We find first- and second-order correlation functions g(1)(tau)
      and g(2)(tau) below and above the generation threshold, and obtain the average
      number of plasmons in the cavity. The latter is shown to be of the order of unity
      near the generation threshold, where the spectral line narrows considerably. In
      this case the coherence is preserved in a state of active atoms in contradiction
      to the good-cavity lasers, where the coherence is preserved in a state of
      photons. The damped oscillations in g(2)(tau) above the generation threshold
      indicate the unusual character of amplitude fluctuations of polarization and
      population, which become interconnected in this case. Obtained results allow to
      understand the fundamental principles of operation of nanolasers.

PMID- 24921562
TI  - Performance of a fire detector based on a compact laser spectroscopic carbon
      monoxide sensor.
AB  - In this paper we show the suitability of a miniaturized tunable diode laser
      spectroscopy (TDLS)-based carbon-monoxide (CO) sensor for fire detection
      applications. The sensor utilizes a vertical-cavity surface-emitting laser
      (VCSEL) and inherent calibration scheme with reference gas filled in the
      photodetector housing. The fire-detection experiments are carried out under
      realistic conditions as described in the European standard EN54. The CO
      generation of all class C fires (according to EN54) could be well resolved. The
      cross-sensitivity to other substances was found to be very low: the maximum CO
      false response from cigarette smoke, hairspray and general aerosols reaches a low
      value of a few MUL/L and only if the substance is directly applied into the
      sensor gas inlet. Therefore this sensor overcomes the disadvantage of high false
      alarm rate given by smoke detectors and is also in small size which is suitable
      for household and industrial applications. Hence, the VCSEL-based TDLS sensor is
      shown to have sufficient performance for fire-detection. It has advantages such
      as capability for fail-safe operation and, low cross-sensitivities as compared to
      existing point fire detector technology which is presently limited by these
      factors. 

PMID- 24921563
TI  - Analytical model for THz emissions induced by laser-gas interaction.
AB  - We develop a one-dimensional model of THz emissions induced by laser-driven, time
      asymmetric ionization and current oscillations in a hydrogen gas. Our model
      highlights complex scalings of the THz fields with respect to the laser and gas
      parameters, in particular, a non-monotonic behavior against the laser parameters.
      Analytical expressions of the transmitted and reflected fields are presented,
      explaining the THz spectra observed in particle-in-cell and forward-pulse
      propagation codes. The backward-propagating THz wave is mainly driven by the
      electron current oscillations at the plasma frequency, and its resulting spectrum
      operates below the plasma frequency. The transmitted THz wave is emitted from
      both plasma current oscillations and photo-ionization. Their respective signal
      presents a contribution below and around the plasma frequency, plus a
      contribution at higher frequencies associated to the photo-induced current. The
      interplay between these two mechanisms relies on the ratio between the
      propagation length and the plasma skin depth. 

PMID- 24921565
TI  - Complete polarimetry on the asymmetric transmission through subwavelength hole
      arrays.
AB  - Dissymmetric, periodically nanostructured metal films can show non-reciprocal
      transmission of polarized light, in apparent violation of the Lorentz reciprocity
      theorem. The wave vector dependence of the extraordinary optical transmission in
      gold films with square and oblique subwavelength hole arrays was examined for the
      full range of polarized light input states. In normal incidence, the oblique
      lattice, in contrast to square lattice, showed strong asymmetric, non-reciprocal
      transmission of circularly polarized light. By analyzing the polarization of the
      input and the output with a complete Mueller matrix polarimeter the mechanisms
      that permits asymmetric transmission while preserving the requirement of
      electromagnetic reciprocity is revealed: the coupling of the linear anisotropies
      induced by misaligned surface plasmons in the film. The square lattice also shows
      asymmetric transmission at non-normal incidence, whenever the plane of incidence
      does not coincide with a mirror line. 

PMID- 24921564
TI  - Three-axis digital holographic microscopy for high speed volumetric imaging.
AB  - Digital Holographic Microscopy allows to numerically retrieve three dimensional
      information encoded in a single 2D snapshot of the coherent superposition of a
      reference and a scattered beam. Since no mechanical scans are involved,
      holographic techniques have a superior performance in terms of achievable frame
      rates. Unfortunately, numerical reconstructions of scattered field by back
      propagation leads to a poor axial resolution. Here we show that overlapping the
      three numerical reconstructions obtained by tilted red, green and blue beams
      results in a great improvement over the axial resolution and sectioning
      capabilities of holographic microscopy. A strong reduction in the coherent
      background noise is also observed when combining the volumetric reconstructions
      of the light fields at the three different wavelengths. We discuss the
      performance of our technique with two test objects: an array of four glass beads
      that are stacked along the optical axis and a freely diffusing rod shaped E.coli
      bacterium. 

PMID- 24921566
TI  - RP-CARS: label-free optical readout of the myelin intrinsic healthiness.
AB  - Here we present a method based on Rotating-Polarization Coherent Anti-Stokes
      Raman Scattering (RP-CARS) imaging to assess the myelin health status in mouse
      sciatic nerves. Differently from the existing techniques, our method is based on
      the readout of intrinsic molecular architecture rather than on the image
      analysis, relying on the fact that healthy myelin is characterized by a high
      degree of molecular order. We exploit RP-CARS imaging to demonstrate that the
      degree of spatial anisotropy of the CARS signal displays a strong correlation
      with the g-ratio (a well-known image-based index of myelin damage) in a chemical
      damage model and therefore that the former is a good indicator for the local
      myelin health status. 

PMID- 24921567
TI  - Generation and subwavelength focusing of longitudinal magnetic fields in a
      metallized fiber tip.
AB  - We demonstrate experimentally and numerically that in fiber tips as they are used
      in NSOMs azimuthally polarized electrical fields (|E(azi)|2 / |E(tot)|2 ~55% +/-
      5% for lambda0 = 1550 nm), respectively subwavelength confined (FWHM ~450 nm
      ~lambda0/3.5) magnetic fields, are generated for a certain tip aperture diameter
      (d = 1.4 MUm). We attribute the generation of this field distribution in metal
      coated fiber tips to symmetry breaking in the bend and subsequent plasmonic mode
      filtering in the truncated conical taper.

PMID- 24921568
TI  - Exploring the potential of optical remote sensing for oil spill detection in
      shallow coastal waters--a case study in the Arabian Gulf.
AB  - Remote sensing provides an effective tool for timely oil pollution response. In
      this paper, the spectral signature in the optical and infrared domains of oil
      slicks observed in shallow coastal waters of the Arabian Gulf was investigated
      with MODIS, MERIS, and Landsat data. Images of the Floating Algae Index (FAI) and
      estimates of sea currents from hydrodynamic models supported the multi-sensor oil
      tracking technique. Scenes with and without sunglint were studied as the spectral
      signature of oil slicks in the optical domain depends upon the viewing geometry
      and the solar angle in addition to the type of oil and its thickness. Depending
      on the combination of those factors, oil slicks may exhibit dark or bright
      contrasts with respect to oil-free waters. Three oil spills events were
      thoroughly analyzed, namely, those detected on May 26 2000 by Landsat 7 ETM + and
      MODIS/Terra, on October 21 2007 by MERIS and MODIS, and on August 17 2013 by
      Landsat 8 and MODIS/Aqua. The oil slick with bright contrast observed by Landsat
      7 ETM + on May 26 2000 showed lower temperature than oil-free areas. The spectral
      Rayleigh-corrected reflectance (R(rc)) signature of oil-covered areas indicated
      higher variability due to differences in oil fractions while the R(rc) spectra of
      the oil-free area were persistent. Combined with RGB composites, FAI images
      showed potentials in differentiating oil slicks from algal blooms. Ocean
      circulation and wind data were used to track oil slicks and forecast their
      potential landfall. The developed oil spill maps were in agreement with official
      records. The synergistic use of satellite observations and hydrodynamic modeling
      is recommended for establishing an early warning and decision support system for
      oil pollution response.

PMID- 24921569
TI  - Ultrasensitive nanomechanical mass sensor using hybrid opto-electromechanical
      systems.
AB  - Nanomechanical resonators provide an unparalleled mass sensitivity sufficient to
      detect single biomolecules, viruses and nanoparticles. In this work we propose a
      scheme for mass sensing based on the hybrid opto-electromechanical system, where
      a mechanical resonator is coupled to an optical cavity and a microwave cavity
      simultaneously. When the two cavities are driven by two pump fields with proper
      frequencies and powers, a weak probe field is used to scan across the optical
      cavity resonance frequency. The mass of a single baculovirus landing onto the
      surface of the mechanical resonator can be measured by tracking the resonance
      frequency shift in the probe transmission spectrum before and after the
      deposition. We also propose a nonlinear mass sensor based on the measurement of
      the four-wave mixing (FWM) spectrum, which can be used to weigh a single 20-nm
      diameter gold nanoparticle with sub-femtogram resolution. 

PMID- 24921570
TI  - Multiple polarization orange and red laser emissions with Pr:BaY2F8.
AB  - We investigated the polarization of continuous-wave laser emission in the orange
      region, at 607 nm, and in the red region, at 639 nm and 643 nm, from a Pr:BaY2F8
      (Pr:BYF) crystal, pumped by a 445 nm laser diode. We achieved linearly polarized
      emission along two optic axes of the crystal by changing its orientation with
      respect to the pump. Simultaneous emission of two orthogonal linear polarizations
      was observed in the orange region, at the same wavelength, and in the red region,
      with concurrent emission from the two separate lines.

PMID- 24921571
TI  - Multichannel-Hadamard calibration of high-order adaptive optics systems.
AB  - we present a novel technique of calibrating the interaction matrix for high-order
      adaptive optics systems, called the multichannel-Hadamard method. In this method,
      the deformable mirror actuators are firstly divided into a series of channels
      according to their coupling relationship, and then the voltage-oriented Hadamard
      method is applied to these channels. Taking the 595-element adaptive optics
      system as an example, the procedure is described in detail. The optimal channel
      dividing is discussed and tested by numerical simulation. The proposed method is
      also compared with the voltage-oriented Hadamard only method and the multichannel
      only method by experiments. Results show that the multichannel-Hadamard method
      can produce significant improvement on interaction matrix measurement. 

PMID- 24921572
TI  - Ultra-long high-sensitivity Phi-OTDR for high spatial resolution intrusion
      detection of pipelines.
AB  - An ultra-long phase-sensitive optical time domain reflectometry (Phi-OTDR) that
      can achieve high-sensitivity intrusion detection over 131.5km fiber with high
      spatial resolution of 8m is presented, which is the longest Phi-OTDR reported to
      date, to the best of our knowledge. It is found that the combination of
      distributed Raman amplification with heterodyne detection can extend the sensing
      distance and enhances the sensitivity substantially, leading to the realization
      of ultra-long Phi-OTDR with high sensitivity and spatial resolution. Furthermore,
      the feasibility of applying such an ultra-long Phi-OTDR to pipeline security
      monitoring is demonstrated and the features of intrusion signal can be extracted
      with improved SNR by using the wavelet detrending/denoising method proposed. 

PMID- 24921573
TI  - A highly flexible platform for nanowire sensor assembly using a combination of
      optically induced and conventional dielectrophoresis.
AB  - The number and position of assembled nanowires cannot be controlled using most
      nanowire sensor assembling methods. In this paper, we demonstrate a high-yield,
      highly flexible platform for nanowire sensor assembly using a combination of
      optically induced dielectrophoresis (ODEP) and conventional dielectrophoresis
      (DEP). With the ODEP platform, optical images can be used as virtual electrodes
      to locally turn on a non-contact DEP force and manipulate a micron- or nano-scale
      substance suspended in fluid. Nanowires were first moved next to the previously
      deposited metal electrodes using optical images and, then, were attracted to and
      arranged in the gap between two electrodes through DEP forces generated by
      switching on alternating current signals to the metal electrodes. A single
      nanowire can be assembled within 24 seconds using this approach. In addition, the
      number of nanowires in a single nanowire sensor can be controlled, and the
      assembly of a single nanowire on each of the adjacent electrodes can also be
      achieved. The electrical properties of the assembled nanowires were characterized
      by IV curve measurement. Additionally, the contact resistance between the
      nanowires and electrodes and the stickiness between the nanowires and substrates
      were further investigated in this study. 

PMID- 24921574
TI  - High resolution heterodyne spectroscopy of the atmospheric methane NIR
      absorption.
AB  - The paper describes the concept of a compact, lightweight heterodyne NIR spectro
      radiometer suitable for atmospheric sounding with solar occultations, and the
      first measurement of CO2 and CH4 absorption near 1.65 MUm with spectral
      resolution lambda/deltalambda~10(8). A highly stabilized DFB laser was used as
      local oscillator, while single model silica fiber Y-coupler served as a diplexer.
      Radiation mixed in the single mode fiber was detected by a balanced couple of
      InGaAs p-i-n diodes within the bandpass of ~3 MHz. Wavelength coverage of
      spectral measurement was provided by sweeping local oscillator frequency in the
      range of 1.1 cm(-1). With the exposure time of 10 min, the absorption spectrum of
      the atmosphere over Moscow has been recorded with S/N ~120, limited by shot
      noise. The inversion algorithm applied to this spectrum resulted in methane
      vertical profile with a maximum mixing ratio of 2148 +/- 10 ppbv near the surface
      and column density 4.59 +/- 0.02.10(22) cm(-2).

PMID- 24921575
TI  - Polarimetric pixel using Seebeck nanoantennas.
AB  - Optical nanoantennas made of two metals are proposed to produce a Seebeck voltage
      proportional to the Stokes parameters of a light beam. The analysis is made using
      simulations in the electromagnetic and thermal domains. Each Stokes parameter is
      independently obtained from a dedicated nanoantenna configuration. S1 and S2 rely
      on the combination of two orthogonal dipoles. S3 is given by arranging two
      Archimedian spirals with opposite orientations. The analysis also includes an
      evaluation of the error associated with the Seebeck voltage, and the crosstalk
      between Stokes parameters. The results could lead to the conception of
      polarization sensors having a receiving area smaller than 10lambda(2). We
      illustrate these findings with a design of a polarimetric pixel.

PMID- 24921576
TI  - Restoration of soft x-ray laser images of nanostructures.
AB  - We present advanced techniques for the restoration of images obtained by soft x
      ray laser microscopy. We show two methods. One method is based on adaptive
      thresholding, while the other uses local Wiener filtering in the wavelet domain
      to achieve high noise gains. These wavelet based denoising techniques are
      improved using spatial noise modeling. The accurate noise model is built up from
      two consecutive images of the object and respective background images. To our
      knowledge, the results of both proposed approaches over-perform competitive
      methods. The analysis is robust to enable image acquisition with significantly
      lower exposure times, which is critical in samples that are sensitive to
      radiation damage as is the case of biological samples imaged by SXR microscopy. 

PMID- 24921577
TI  - Beam characteristics of fiber-based supercontinuum light sources with mirror- and
      lens-based beam collimators.
AB  - Commercially available supercontinuum light sources that cover most of the solar
      spectrum are well suited for instrumentation, where a well-collimated beam with
      wide spectral coverage is needed. Typically, the optical power is emitted from a
      single-mode photonic-crystal fiber and the output can either be collimated using
      a proprietary, permanently integrated, lens-based collimator or with a customer
      provided, off-axis parabolic mirror. Here, we evaluate both approaches and
      conclude that, superior beam quality and collimation over the whole spectral
      range can be obtained with an off-axis parabolic mirror, however at the price of
      a more complex and bulky system requiring additional user alignment. 

PMID- 24921579
TI  - Compensating the electron beam energy spread by the natural transverse gradient
      of laser undulator in all-optical x-ray light sources.
AB  - All-optical ideas provide a potential to dramatically cut off the size and cost
      of x-ray light sources to the university-laboratory scale, with the combination
      of the laser-plasma accelerator and the laser undulator. However, the large
      longitudinal energy spread of the electron beam from laser-plasma accelerator may
      hinder the way to high brightness of these all-optical light sources. In this
      paper, the beam energy spread effect is proposed to be significantly compensated
      by the natural transverse gradient of a laser undulator when properly transverse
      dispersing the electron beam. Theoretical analysis and numerical simulations on
      conventional laser-Compton scattering sources and high-gain all-optical x-ray
      free-electron lasers with the electron beams from laser-plasma accelerators are
      presented. 

PMID- 24921578
TI  - White light wavefront control with a spatial light modulator.
AB  - Spatial light modulators are ubiquitous tools for wavefront control and laser
      beam shaping but have traditionally been used with monochromatic sources due to
      the inherent wavelength dependence of the calibration process and subsequent
      phase manipulation. In this work we show that such devices can also be used to
      shape broadband sources without any wavelength dependence on the output beam's
      phase. We outline the principle mathematically and then demonstrate it
      experimentally using a supercontinuum source to shape rotating white-light Bessel
      beams carrying orbital angular momentum. 

PMID- 24921580
TI  - Cavity-enhanced optical frequency comb spectroscopy of high-temperature H2O in a
      flame.
AB  - We demonstrate near-infrared cavity-enhanced optical frequency comb spectroscopy
      of water in a premixed methane/air flat flame. The detection system is based on
      an Er:fiber femtosecond laser, a high finesse optical cavity containing the
      flame, and a fast-scanning Fourier transform spectrometer (FTS). High absorption
      sensitivity is obtained by the combination of a high-bandwidth two-point comb
      cavity lock and auto-balanced detection in the FTS. The system allows recording
      high-temperature water absorption spectra with a resolution of 1 GHz and a
      bandwidth of 50 nm in an acquisition time of 0.4 s, with absorption sensitivity
      of 4.2 * 10(-9) cm(-1) Hz(-1/2) per spectral element.

PMID- 24921581
TI  - High-resolution optical see-through multi-focal-plane head-mounted display using
      freeform optics.
AB  - Conventional stereoscopic displays force an unnatural decoupling of the
      accommodation and convergence cues, which may contribute to various visual
      artifacts and have adverse effects on depth perception accuracy. In this paper,
      we present the design and implementation of a high-resolution optical see-through
      multi-focal-plane head-mounted display enabled by state-of-the-art freeform
      optics. The prototype system is capable of rendering nearly-correct focus cues
      for a large volume of 3D space, extending into a depth range from 0 to 3
      diopters. The freeform optics, consisting of a freeform prism eyepiece and a
      freeform lens, demonstrates an angular resolution of 1.8 arcminutes across a 40
      degree diagonal field of view in the virtual display path while providing a 0.5
      arcminutes angular resolution to the see-through view. 

PMID- 24921582
TI  - Optimizing sub-ns pulse compression for high energy application.
AB  - We demonstrate ~ 40X pulse compression (down to ~ 300 ps) with ~ 1 joule,
      nanosecond pulses for high energy applications requiring >= 1 gigawatt of peak
      power. Our method is based on the established principle of stimulated Brillouin
      scattering (SBS). To push the SBS technique to its highest peak-power limit, a
      combination of theoretical modeling and experiments is used to identify and
      optimize all critical parameters, including optical configuration, interaction
      length, intensity matching, choice of gain medium and thermal stability. Pulse
      compression results are presented both at 1064 nm and 532 nm, with performances
      close to the theoretical limit and excellent shot-to-shot reproducibility. 

PMID- 24921583
TI  - A packaged, low-cost, robust optical fiber strain sensor based on small cladding
      fiber sandwiched within periodic polymer grating.
AB  - In the present study, a novel packaged long-period fiber grating (PLPFG) strain
      sensor is first presented. The MEMS process was utilized to fabricate the
      packaged optical fiber strain sensor. The sensor structure consisted of etched
      optical fiber sandwiched between two layers of thick photoresist SU-8 3050 and
      then packaged with poly (dimethylsiloxane) (PDMS) polymer material to construct
      the PLPFG strain sensor. The PDMS packaging material was used to prevent the glue
      effect, wherein glue flows into the LPFG structure and reduces coupling strength,
      in the surface bonding process. Because the fiber grating was packaged with PDMS
      material, it was effectively protected and made robust. The resonance attenuation
      dip of PLPFG grows when it is loading. This study explored the size effect of the
      grating period and fiber diameter of PLPFG via tensile testing. The experimental
      results found that the best strain sensitivity of the PLPFG strain sensor was 
      0.0342 dB/MUepsilon, and that an R2 value of 0.963 was reached.

PMID- 24921584
TI  - Discrete solitons and scattering of lattice waves in guiding arrays with a
      nonlinear PT-symmetric defect.
AB  - Discrete fundamental and dipole solitons are constructed, in an exact analytical
      form, in an array of linear waveguides with an embedded PT-symmetric dimer, which
      is composed of two nonlinear waveguides carrying equal gain and loss. Fundamental
      solitons in tightly knit lattices, as well as all dipole modes, exist above a
      finite threshold value of the total power. However, the threshold vanishes for
      fundamental solitons in loosely knit lattices. The stability of the discrete
      solitons is investigated analytically by means of the Vakhitov-Kolokolov (VK)
      criterion, and, in the full form, via the computation of eigenvalues for
      perturbation modes. Fundamental and dipole solitons tend to be stable at smaller
      and larger values of the total power (norm), respectively. The increase of the
      strength of the coupling between the two defect-forming sites leads to strong
      expansion of the stability areas. The scattering problem for linear lattice waves
      impinging upon the defect is considered too.

PMID- 24921585
TI  - Controlling rejections of spoof surface plasmon polaritons using metamaterial
      particles.
AB  - Based on the dispersion relation, surface plasmon polaritons (SPPs) or spoof SPPs
      are always propagating surface waves when the operating frequency is below the
      asymptotic limit - the surface plasma frequency. Here we propose a method to
      control the rejections of spoof SPPs using metamaterial particles. By introducing
      electrically resonant metamaterials near an ultrathin corrugated metallic strip -
      the spoof SPP waveguide - to produce tight coupling and mismatch of surface
      impedance, we show that the SPP modes are rejected near the resonant frequencies
      within the propagating band. Through the modulation of scaling factor of
      metamaterial particles, we can manipulate the rejections of SPP modes from
      narrowband to broadband. Both simulation and experiment results verify the
      tunability of SPP rejections, which have important applications in filtering SPP
      waves in plasmonic circuits and systems. 

PMID- 24921586
TI  - Efficient fabrication of ultrasmooth and defect-free quartz glass surface by
      hydrodynamic effect polishing combined with ion beam figuring.
AB  - Material removal rate has greatly relied on the distribution of shear stress and
      dynamic pressure on the workpiece surface in hydrodynamic effect polishing (HEP).
      Fluid dynamic simulation results demonstrate that the higher rotation speed and
      smaller clearance will cause the larger material removal rate. Molecular dynamic
      (MD) calculations show the bonding energy of Si-O in the silicon-oxide
      nanoparticle is stronger than that in the quartz glass, and therefore the atoms
      can be dragged away from the quartz glass surface by the adsorbed silicon-oxide
      nanoparticle. The deep subsurface damage cannot be efficiently removed by HEP due
      to its extremely low removal rate. However, the subsurface damaged layer can be
      quickly removed by ion beam figuring (IBF), and a thinner layer containing the
      passivated scratches and pits will be left on the surface. The passivated layer
      is so thin that can be easily removed by HEP process with a low material rate
      under the large wheel-workpiece clearance. Combined with the IBF process, the
      subsurface damage and surface scratches have been efficiently removed after the
      HEP process. Meanwhile there are not obvious duplicated marks on the processed
      surface and the surface roughness has been improved to 0.130nm rms, 0.103nm Ra. 

PMID- 24921587
TI  - Ytterbium-doped large-mode-area all-solid photonic bandgap fiber lasers.
AB  - Single-mode operation in a large-mode-area fiber laser is highly desired for
      power scaling. We have, for the first time, demonstrated a 50MUm-core-diameter Yb
      doped all-solid photonic bandgap fiber laser with a mode area over 4 times that
      of the previous demonstration. 75W output power has been generated with a
      diffraction-limited beam and an efficiency of 70% relative to the launched pump
      power. We have also experimentally confirmed that a robust single-mode regime
      exists near the high frequency edge of the bandgap. These fibers only guide light
      within the bandgap over a narrow spectral range, which is essential for lasing
      far from the gain peak and suppression of stimulated Raman scattering. This work
      demonstrates the strong potential for mode area scaling of in single-mode all
      solid photonic bandgap fibers. 

PMID- 24921588
TI  - Diode-pumped 1.5-1.6 MUm laser operation in Er3+ doped YbAl3(BO3)4 microchip.
AB  - Er3+ doped YbAl3(BO3)4 crystal with large absorption coefficient of 184 cm(-1) at
      pump wavelength of 976 nm is a promising microchip gain medium of 1.5-1.6 MUm
      laser. End-pumped by a 976 nm diode laser, 1.5-1.6 MUm continuous-wave laser with
      maximum output power of 220 mW and slope efficiency of 8.1% was obtained at
      incident pump power of 4.54 W in a c-cut 200-MUm-thick Er:YbAl3(BO3)4 microchip.
      When a Co2+:Mg0.4Al2.4O4 crystal was used as the saturable absorber, 1521 nm
      passively Q-switched pulse laser with about 0.19 MUJ energy, 265 ns duration, and
      96 kHz repetition rate was realized.

PMID- 24921589
TI  - Elliptical Laguerre-Gaussian correlated Schell-model beam.
AB  - A new kind of partially coherent beam with non-conventional correlation function
      named elliptical Laguerre-Gaussian correlated Schell-model (LGCSM) beam is
      introduced. Analytical propagation formula for an elliptical LGCSM beam passing
      through a stigmatic ABCD optical system is derived. The elliptical LGCSM beam
      exhibits unique features on propagation, e.g., its intensity in the far field (or
      in the focal plane) displays an elliptical ring-shaped beam profile, being
      qualitatively different from the circular ring-shaped beam profile of the
      circular LGCSM beam. Furthermore, we carry out experimental generation of an
      elliptical LGCSM beam with controllable ellipticity, and measure its focusing
      properties. Our experimental results are consistent with the theoretical
      predictions. The elliptical LGCSM beam will be useful in atomic optics. 

PMID- 24921590
TI  - Algorithm for evaluation of temperature distribution of a vapor cell in a diode
      pumped alkali laser system: part I.
AB  - A diode-pumped alkali laser (DPAL) is one of the most hopeful candidates to
      achieve high power performances. As the laser medium is in a gas-state,
      populations of energy-levels of a DPAL are strongly dependent on the vapor
      temperature. Thus, the temperature distribution directly determines the output
      characteristics of a DPAL. In this report, we developed a systematic model by
      combining the procedures of heat transfer and laser kinetics together to explore
      the radial temperature distribution in the transverse section of a cesium vapor
      cell. A cyclic iterative approach is adopted to calculate the population
      densities. The corresponding temperature distributions have been obtained for
      different beam waists and pump powers. The conclusion is thought to be useful for
      realizing a DPAL with high output power. 

PMID- 24921591
TI  - Coupled-resonator optical waveguides for temporal integration of optical signals.
AB  - In this paper, we propose and numerically investigate an all-optical temporal
      integrator based on a photonic crystal cavity. We show that an array of photonic
      crystal cavities enables high-order temporal integration. The effect of the value
      of the cavity's free spectral range on the accuracy of the integration is
      considered. The influence of the coupling coefficients in the resonator array on
      the integration accuracy is demonstrated. A compact integrator based on a
      photonic crystal nanobeam cavity is designed, which allows high-precision
      integration of optical pulses of subpicosecond duration. 

PMID- 24921592
TI  - Plasmon assisted enhanced nonlinear refraction of monodispersed silver
      nanoparticles and their tunability.
AB  - Nonlinear optical characterizations were performed on monodispersed silver (Ag)
      nanoparticles (NPs) of various sizes using a picosecond Z-scan technique with
      excitation wavelengths of 532 nm and 1064 nm. The Ag NPs were fabricated using a
      heterogeneous condensation technique in a gas medium. The nonlinear refraction
      values were higher for the monodispersed Ag NPs whose surface plasmon resonance
      (SPR) peak is closer to the excitation wavelength. The higher nonlinear optical
      response is explained in terms of an electric field enhancement near the SPR.
      Moreover, the fabrication method allows the tailoring of the nonlinear refraction
      index of the Ag NPs by tuning the SPR peak of the sample. A comparison of the
      nonlinear refraction index of the monodispersed and polydispersed Ag NPs showed
      that the nonlinear refractive index of the monodispersed Ag NPs is higher. 

PMID- 24921593
TI  - Tunable bulk polaritons of graphene-based hyperbolic metamaterials.
AB  - The tunable hyperbolic metamaterial (HMM) based on the graphene-dielectric
      layered structure at THz frequency is presented, and the surface and bulk
      polaritons of the graphene-based HMM are theoretically studied. It is found that
      the dispersions of the polaritons can be tuned by varying the Fermi energy of
      graphene sheets, the graphene-dielectric layers and the layer number of graphene
      sheets. In addition, the highly confined bulk polariton mode can be excited and
      is manifested in an attenuated total reflection configuration as a sharp drop in
      the reflectance. Such properties can be used in tunable optical reflection
      modulation with the assistance of bulk polaritons. 

PMID- 24921594
TI  - All-digital wavefront sensing for structured light beams.
AB  - We present a new all-digital technique to extract the wavefront of a structured
      light beam. Our method employs non-homogeneous polarization optics together with
      dynamic, digital holograms written to a spatial light modulator to measure the
      phase relationship between orthogonal polarization states in real-time, thereby
      accessing the wavefront information. Importantly, we show how this can be applied
      to measuring the wavefront of propagating light fields, over extended distances,
      without any moving components. We illustrate the versatility of the tool by
      measuring propagating optical vortices, Bessel, Airy and speckle fields. The
      comparison of the extracted and programmed wavefronts yields excellent agreement.

PMID- 24921596
TI  - Identifying the molecular basis of host-parasite coevolution: merging models and
      mechanisms.
AB  - Mathematical models of the coevolutionary process have uncovered consequences of
      host-parasite interactions that go well beyond the traditional realm of the Red
      Queen, potentially explaining several important evolutionary transitions.
      However, these models also demonstrate that the specific consequences of
      coevolution are sensitive to the structure of the infection matrix, which is
      embedded in models to describe the likelihood of infection in encounters between
      specific host and parasite genotypes. Traditional cross-infection approaches to
      estimating infection matrices might be unreliable because evolutionary dynamics
      and experimental sampling lead to missing genotypes. Consequently, our goal is to
      identify the likely structure of infection matrices by synthesizing molecular
      mechanisms of host immune defense and parasite counterdefense with coevolutionary
      models. This synthesis reveals that the molecular mechanisms of immune reactions,
      although complex and diverse, conform to two basic models commonly used within
      coevolutionary theory: matching infection and targeted recognition. Our synthesis
      also overturns conventional wisdom, revealing that the general models are not
      taxonomically restricted but are applicable to plants, invertebrates, and
      vertebrates. Finally, our synthesis identifies several important areas for future
      research that should improve the explanatory power of coevolutionary models. The
      most important among these include empirical studies to identify the molecular
      hotspots of genotypic specificity and theoretical studies examining the
      consequences of matrices that more accurately represent multistep infection
      processes and quantitative defenses.

PMID- 24921595
TI  - A partial hearing animal model for chronic electro-acoustic stimulation.
AB  - OBJECTIVE: Cochlear implants (CIs) have provided some auditory function to
      hundreds of thousands of people around the world. Although traditionally carried
      out only in profoundly deaf patients, the eligibility criteria for implantation
      have recently been relaxed to include many partially-deaf patients with useful
      levels of hearing. These patients receive both electrical stimulation from their
      implant and acoustic stimulation via their residual hearing (electro-acoustic
      stimulation; EAS) and perform very well. It is unclear how EAS improves speech
      perception over electrical stimulation alone, and little evidence exists about
      the nature of the interactions between electric and acoustic stimuli.
      Furthermore, clinical results suggest that some patients that undergo cochlear
      implantation lose some, if not all, of their residual hearing, reducing the
      advantages of EAS over electrical stimulation alone. A reliable animal model with
      clinically-relevant partial deafness combined with clinical CIs is important to
      enable these issues to be studied. This paper outlines such a model that has been
      successfully used in our laboratory. APPROACH: This paper outlines a battery of
      techniques used in our laboratory to generate, validate and examine an animal
      model of partial deafness and chronic CI use. MAIN RESULTS: Ototoxic deafening
      produced bilaterally symmetrical hearing thresholds in neonatal and adult
      animals. Electrical activation of the auditory system was confirmed, and all
      animals were chronically stimulated via adapted clinical CIs. Acoustic compound
      action potentials (CAPs) were obtained from partially-hearing cochleae, using the
      CI amplifier. Immunohistochemical analysis allows the effects of deafness and
      electrical stimulation on cell survival to be studied. SIGNIFICANCE: This animal
      model has applications in EAS research, including investigating the functional
      interactions between electric and acoustic stimulation, and the development of
      techniques to maintain residual hearing following cochlear implantation. The
      ability to record CAPs via the CI has clinical direct relevance for obtaining
      objective measures of residual hearing.

PMID- 24921598
TI  - Keeping pace with climate change: stage-structured moving-habitat models.
AB  - Life cycles can limit the abilities of species to track changing climatic
      conditions. We combined age or stage structure and a moving-habitat model to
      explore the effects of life history on the persistence of populations in the
      presence of climate change. We studied four dissimilar plant species in moving
      patches and found that (1) population growth rates, (2) elasticities with respect
      to the survival (stasis and shrinkage) components of the projection matrix, and
      (3) the evenness of the elasticities with respect to the components of the
      projection matrix all decreased as we increased the translational speeds of the
      patches. In addition, the value of long-distance dispersal increased with patch
      speed for three of the four species. Our analyses confirm that rapid growth, high
      fecundity, and long-distance dispersal can benefit species in moving patches.
      Thus, species with long generation times and limited dispersal ability are
      especially vulnerable to habitat movement. Stage-structured moving-habitat models
      can easily incorporate spatial complexity and can help us predict the effects of
      shifting climatic conditions.

PMID- 24921597
TI  - Conceptual and empirical challenges of ascribing functions to transposable
      elements.
AB  - Media attention and the subsequent scientific backlash engendered by the claim by
      spokespeople for the Encyclopedia of DNA Elements (ENCODE) project that 80% of
      the human genome has a biochemical function highlight the need for a clearer
      understanding of function concepts in biology. This article provides an overview
      of two major function concepts that have been developed in the philosophy of
      science--the causal role concept and the selected effects concept--and their
      relevance to ENCODE. Unlike in some previous critiques, the ENCODE project is not
      considered problematic here because it employed a causal role definition of
      function (which is relatively common in genetics) but because of how this concept
      was misused. In addition, several unique challenges that arise when dealing with
      transposable elements (TEs) but that were ignored by ENCODE are highlighted.
      These include issues surrounding TE-level versus organism-level selection, the
      origins versus the persistence of elements, and accidental versus functional
      organism-level benefits. Finally, some key questions are presented that should be
      addressed in any study aiming to ascribe functions to major portions of large
      eukaryotic genomes, the majorities of which are made up of transposable elements.

PMID- 24921599
TI  - Gender-specific emigration decisions sensitive to local male and female density.
AB  - Increasing interest is directed on understanding how individuals utilize
      information to come to dispersal decisions. We assume individuals base emigration
      decisions on male and female density in their natal patches. We derive gender
      specific functions for emigration probability of species with discrete
      generations and polygynous mating under the premise that dispersal strategies
      equalize fitness expectations of emigrants and philopatric individuals: migration
      decisions should then always depend on a critical threshold density of the own
      gender. Whether density of the opposite sex affects emigration depends on details
      of resource competition: (1) Without competition, females should never emigrate,
      while males should emigrate in response to local sex ratio. (2) Under extreme
      competition among females or offspring, females and males should respond to the
      local density of their own gender only. (3) If both sexes compete over resources,
      emigration responds to the density of both sexes, but the dependence differs
      quantitatively between females and males. (4) Male-biased dispersal is the
      general expectation for polygynous species, but the model allows specifying
      conditions under which more females than males might nonetheless emigrate. The
      model provides guidelines for implementing density-dependent dispersal in
      simulations and specifies principal patterns that should emerge in empirical
      data.

PMID- 24921600
TI  - Dispersal capacity predicts both population genetic structure and species
      richness in reef fishes.
AB  - Dispersal is a fundamental species characteristic that should directly affect
      both rates of gene flow among spatially distributed populations and opportunities
      for speciation. Yet no single trait associated with dispersal has been
      demonstrated to affect both micro- and macroevolutionary patterns of diversity
      across a diverse biological assemblage. Here, we examine patterns of genetic
      differentiation and species richness in reef fishes, an assemblage of over 7,000
      species comprising approximately one-third of the extant bony fishes and over one
      tenth of living vertebrates. In reef fishes, dispersal occurs primarily during a
      planktonic larval stage. There are two major reproductive and parental investment
      syndromes among reef fishes, and the differences between them have implications
      for dispersal: (1) benthic guarding fishes lay negatively buoyant eggs, typically
      guarded by the male parent, and from these eggs hatch large, strongly swimming
      larvae; in contrast, (2) pelagic spawning fishes release small floating eggs
      directly into the water column, which drift unprotected before small weakly
      swimming larvae hatch. Using phylogenetic comparative methods, we show that
      benthic guarders have significantly greater population structure than pelagic
      spawners and additionally that taxonomic families of benthic guarders are more
      species rich than families of pelagic spawners. Our findings provide a compelling
      case for the continuity between micro- and macroevolutionary processes of
      biological diversification and underscore the importance of dispersal-related
      traits in influencing the mode and tempo of evolution.

PMID- 24921601
TI  - Inferring host range dynamics from comparative data: the protozoan parasites of
      new world monkeys.
AB  - Uncovering the ecological determinants of parasite host range is a central goal
      of comparative parasitology and infectious disease ecology. But while parasites
      are often distributed nonrandomly across the host phylogeny, such patterns are
      difficult to interpret without a genealogy for the parasite samples and without
      knowing what sorts of ecological dynamics might lead to what sorts of
      nonrandomness. We investigated inferences from comparative data, using
      presence/absence records from protozoan parasites of the New World monkeys. We
      first demonstrate several distinct types of phylogenetic signal in these data,
      showing, for example, that parasite species are clustered on the host tree and
      that closely related host species harbor similar numbers of parasite species. We
      then show that all of these patterns can be generated by a single, simple
      dynamical model, in which parasite host range changes more rapidly than host
      speciation/extinction and parasites preferentially colonize uninfected host
      species that are closely related to their existing hosts. Fitting this model to
      data, we then estimate its parameters. Finally, we caution that quite different
      ecological processes can lead to similar signatures but show how phylogenetic
      variation in host susceptibility can be distinguished from a tendency for
      parasites to colonize closely related hosts. Our new process-based analyses,
      which estimate meaningful parameters, should be useful for inferring the
      determinants of parasite host range and transmission success.

PMID- 24921602
TI  - Parental optimism versus parental pessimism in plants: how common should we
      expect pollen limitation to be?
AB  - Many organisms exhibit parental optimism, producing more of the initial stages of
      offspring (e.g., eggs, embryos) than they can usually mature. For plants,
      parental optimism may be linked to the risk of seed production being limited by
      pollen receipt (pollen limitation). Here we elaborate a stochastic model of
      pollen limitation developed by Haig and Westoby ( 1988 ) and Burd ( 2008 ) and
      link it with published data on the magnitudes of prepollination costs versus
      postpollination costs of seed production in 80 plant species. We demonstrate that
      parental optimism should be expected when prepollination costs of seed production
      are small relative to postpollination costs. This was observed for most (62 of
      80) of the plant taxa surveyed. Under parental optimism, plants overinvest in
      securing fertilized ovules, and consequently pollen limitation is predicted to be
      uncommon. However, for a sizable minority of plant species (18 of 80),
      prepollination costs approach or exceed postpollination costs. For these species,
      parental pessimism is instead optimal. Parents initiate fewer zygotes than they
      can usually mature, and pollen limitation is predicted to be severe. Because the
      relative magnitudes of prepollination and postpollination costs vary by more than
      1,000-fold across plant taxa, parental outlook (optimism vs. pessimism) and
      levels of pollen limitation are predicted to vary widely.

PMID- 24921603
TI  - Predator-mediated natural selection on the wings of the damselfly Calopteryx
      splendens: differences in selection among trait types.
AB  - Traits that increase mating success in males may come at a cost, such as an
      increased risk of predation. However, predator-mediated selection is challenging
      to document in natural populations, hampering our understanding of the trade-offs
      between sexual selection and predation. Here we report on a study of predator
      mediated natural selection on wing traits in the damselfly Calopteryx splendens,
      the males of which possess conspicuous wing patches. Wagtails (genus Motacilla)
      are important avian predators of C. splendens, capturing them in flight and
      removing the wings prior to consumption. Using geometric morphometric techniques,
      we quantified the strength and mode of selection on wing traits by comparing
      wings from depredated individuals with the standing variation present in the
      population. Our results reveal that predator-mediated selection is stronger on
      secondary sexual characters than on size and shape, suggesting that traits
      related to flight performance are closer to their adaptive peaks. This could be a
      consequence of the long-term evolutionary association with avian predators,
      whereas stronger selection on conspicuous secondary sexual traits may reflect
      trade-offs between sexual and natural selection. Finally, even though C.
      splendens possesses nearly identical fore- and hindwings, we found evidence for
      divergent selection between them.

PMID- 24921604
TI  - Killing and replacing queen-laid eggs: low cost of worker policing in the
      honeybee.
AB  - Worker honeybees, Apis mellifera, police each other's reproduction by killing
      worker-laid eggs. Previous experiments demonstrated that worker policing is
      effective, killing most (~98%) worker-laid eggs. However, many queen-laid eggs
      were also killed (~50%) suggesting that effective policing may have high costs.
      In these previous experiments, eggs were transferred using forceps into test
      cells, mostly into unrelated discriminator colonies. We measured both the
      survival of unmanipulated queen-laid eggs and the proportion of removal errors
      that were rectified by the queen laying a new egg. Across 2 days of the 3-day egg
      stage, only 9.6% of the queen-laid eggs in drone cells and 4.1% in worker cells
      were removed in error. When queen-laid eggs were removed from cells, 85% from
      drone cells and 61% from worker cells were replaced within 3 days. Worker
      policing in the honeybee has a high benefit to policing workers because workers
      are more related to the queen's sons (brothers, r = 0.25) than sister workers'
      sons (0.15). This study shows that worker policing also has a low cost in terms
      of the killing of queen-laid eggs, as only a small proportion of queen-laid eggs
      are killed, most of which are rapidly replaced.

PMID- 24921605
TI  - Evolutionary constraints in high-dimensional trait sets.
AB  - Genetic variation for individual traits is typically abundant, but for some
      multivariate combinations it is very low, suggesting that evolutionary limits
      might be generated by the geometric distribution of genetic variance. To test
      this prediction, we artificially selected along all eight genetic eigenvectors of
      a set of eight quantitative traits in Drosophila serrata. After six generations
      of 50% truncation selection, at least one replicate population of all treatments
      responded to selection, allowing us to reject a null genetic subspace as a cause
      of evolutionary constraint in this system. However, while all three replicate
      populations of the first five selection treatments displayed a significant
      response, the remaining three, characterized by low genetic variance in their
      selection indexes in the base population, displayed inconsistent responses to
      selection. The observation that only four of the nine replicate populations
      evolved in response to the direct selection applied to them in these low genetic
      variance treatments, led us to conclude that a nearly null subspace did limit
      evolution. Dimensions associated with low genetic variance are often found in
      multivariate analyses of standing genetic variance in morphological traits,
      suggesting that the nearly null genetic subspace may be a common mechanism of
      evolutionary constraint in nature.

PMID- 24921606
TI  - Comparison of natural and nonnative two-species communities of Anolis lizards.
AB  - Human-mediated colonizations present an informative model system for
      understanding assembly of organismal communities. However, it is unclear whether
      communities including naturalized species are accurate analogs of natural
      communities or unique combinations not present in nature. I compared morphology
      and phylogenetic structure of natural and naturalized two-species communities of
      Anolis lizards. Natural communities are phylogenetically clustered, whereas
      naturalized communities show no significant phylogenetic structure. This result
      likely reflects differences in colonization pools for these communities-that is,
      invasion from anywhere for naturalized communities but from proximal and thus
      phylogenetically close lineages in natural communities. Both natural and
      naturalized communities each include pairs of species that are significantly
      similar to each other in morphology, and both sets of communities are composed of
      species that possess traits of good colonizers. These similarities suggest that
      the formation of natural and naturalized communities may be at least partially
      governed by similar processes. Human-mediated invasions may be credibly viewed as
      modern incarnations of natural colonizations in this case.

PMID- 24921607
TI  - The evolution of bet hedging in response to local ecological conditions.
AB  - Genotypes that hedge their bets can be favored by selection in an unpredictably
      varying environment. Bet hedging can be achieved by systematically expressing
      several phenotypes, such as one that readily attempts to reproduce and one that
      procrastinates in a dormant stage. But how much of each phenotype should a
      genotype express? Theory predicts that evolving bet-hedging strategies depend on
      local environmental variation, on how the population is regulated, and on
      exchanges with neighboring populations. Empirically, however, it remains unknown
      whether bet hedging can evolve to cope with the ecological conditions experienced
      by populations. Here we study the evolution of bet-hedging dormancy frequencies
      in two neighboring populations of the chestnut weevil, Curculio elephas. We
      estimate the temporal distribution of demographic parameters together with the
      form of the relationship between fecundity and population density and use both to
      parameterize models that predict the bet-hedging dormancy frequency expected to
      evolve in each population. Strikingly, the observed dormancy frequencies closely
      match predictions in their respective localities. We also found that dormancy
      frequencies vary randomly across generations, likely due to environmental
      perturbations of the underlying physiological mechanism. Using a model that
      includes these constraints, we predict the whole distribution of dormancy
      frequencies whose mean and shape agree with our observed data. Overall, our
      results suggest that dormancy frequencies have evolved according to local
      ecological conditions and physiological constraints.

PMID- 24921608
TI  - Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref)
      in north Indian patients with bronchial asthma: an evaluation using Rasch
      analysis.
AB  - BACKGROUND: There is no disease-specific instrument to describe health-related
      quality of life (HRQoL) in Indian patients with asthma. However, an abbreviated
      World Health Organization Quality of Life questionnaire (WHOQOL-Bref), a generic
      Hindi HRQoL measure, has been developed and validated in India. AIMS: To evaluate
      the WHOQOL-Bref in adult patients with asthma and to test possible modifications
      to the instrument to improve its psychometric adequacy. METHODS: Sixty-seven
      patients with asthma completed the WHOQOL-Bref. Rasch analysis was used to
      explore the psychometric performance of the four domains (physical,
      psychological, social relationships and environment) of the scale. Overall fit of
      data to model expectations, appropriate category ordering, presence of
      differential item functioning, individual item fit and targeting of item
      difficulty to patient ability were explored for each domain. Item deletion and
      rescoring were applied to misfitting items to improve overall performance.
      RESULTS: The overall fit of the WHOQOL-Bref data was adequate. Item 3 (pain
      prevents doing work) displayed a large positive fit residual value (indicating
      violation of unidimensionality), resulting in poor construct validity for the
      physical domain. No item exhibited differential item functioning. Ten items had
      disordered thresholds. The WHOQOL-Bref was modified by dropping item 3 and
      rescoring category structures of 16 items. The modified scale had good construct
      validity for all domains, ordered thresholds for all items and good targeting of
      items to persons. CONCLUSIONS: The WHOQOL-Bref performed inadequately in
      describing HRQoL in the asthma patients studied. However, when modified by Rasch
      analysis, the scale proved better than the original scale.

PMID- 24921609
TI  - How accurate are Omron X-HJ-304-E and Yamax SW-700/701 pedometers at different
      speeds and various inclinations?
AB  - AIM: The purpose of this study was to investigate step count and energy
      expenditure accuracy of the piezoelectric Omron (Walking Style X-HJ-304-E) and
      spring-levered Yamax (Digi-Walker-SW-700/701) pedometers at different speeds and
      various inclinations. METHODS: Thirty subjects (15 females, aged: 24 +/- 3 years)
      completed eleven 5-min trials at different treadmill speeds and inclinations
      (3.24 km?h-1 [inclination: 0, 9, 20%], 4.68 km?h-1 [0, 9, 20%], 6.48 km?h-1 [0,
      9%], 9 km?h-1 [0%], 10.8 km?h-1 [0%], 12.6 km?h-1 [0%]). During each trial, an
      investigator recorded actual steps with a hand tally counter. Actual energy
      expenditure was measured using a portable indirect calorimeter. RESULTS: The
      Omron pedometer revealed high step count accuracy for all speeds and inclinations
      when worn on the hip or a backpack (Mean % of actual steps: 99.6%; Range: 95.8
      101.3%). The Yamax pedometer revealed high step count accuracy (Mean % of actual
      steps: 99.8%; Range: 96.2-103.3%) when worn on the left hip at 6.48-12.6 km?h-1
      (0%), 4.68 km?h-1 (9%, 20%), 6.48 km?h-1 (9%) and on the right hip at 10.8 km?h-1
      (0%) and 6.48 km?h-1 (9%). The accuracy of the Omron and Yamax determined energy
      expenditure was poor (57.9-59.7%) when compared to indirect calorimetry.
      CONCLUSION: The Omron pedometer provides accurate step counts when worn on the
      hip and backpack at all tested speeds and inclinations. We therefore suggest an
      accurate application of this device for walking, hiking and running at moderate
      speeds. Both pedometers underestimated energy expenditure.

PMID- 24921610
TI  - The impact of high level basketball competition, calcium intake, menses, and
      hormone levels in adolescent bone density: a three-year follow-up.
AB  - AIM: The main goal of the present work is to establish the positive influence
      high-impact physical exercise, specifically high-level basketball, on bone
      acquisition in adolescent female and verify if the long-term exposure to such
      programs is the major modifiable factor explaining bone acquisition during
      adolescence. METHODS: A prospective cohort study comparing the development of
      bone mass in the lumbar spine, proximal femur and distal radius was carried out
      over a three-year period in two groups of adolescents: elite basketball players
      and age-matched controls. Baseline hormone levels and bone remodelling were
      evaluated. Bone mass, hours of physical exercise, diet, unhealthy habits,
      anthropometry and menstrual cycle were assessed at baseline and yearly.
      Differences in acquisition of bone mass were assessed by two-way repeated
      measures analysis of variance (ANOVA). RESULTS: Elite basketball training and
      competition appears to increase bone mass in girls aged 14-18 years. The most
      pronounced benefits were observed in lumbar spine and proximal femur, sites most
      directly involved in the exercise and subjected to greatest impact. CONCLUSION:
      The intensive basketball training and competition in adolescent females increases
      bone mass in the lumbar spine and femur, skeletal sites submitted to high impact
      in this sport. No significant gain in bone mass was observed in age-matched,
      normally active, controls.

PMID- 24921611
TI  - Improving neuromuscular performance in young basketball players: plyometric vs.
      technique training.
AB  - AIM: The aim of this study was to compare the effects of plyometric training
      versus basketball technique training on improving neuro-muscular performance.
      METHODS: Thirty-six (age 14.9+/-0.9 years, body height 164.0+/-7.6 cm, body
      weight 54.0+/-8.7 kg, BMI 20.1+/-2.4 kg.m-2) basketball players girls were
      randomly allocated to 2 groups: Basketball Plyometric Training (BPT, N.=18) and
      Basketball Technique Training (BTT, N.=18). The players were tested by two
      specific tests: counter movement jump (CMJ) and squat jump (SJ) before and after
      6 training weeks. RESULTS: The jump height, as dependent variable, showed a
      different trend as an effect of the different training protocols, in contrast
      with the current knowledge. Manova did not show significant interactions between
      the two groups for the height of jumps, while significant differences were found
      for interaction time * training (P<0.05) and for main effect * time (P<0.001).
      After training, the BPT group increased significantly CMJ performance by 11.3%
      (P<0.05), whereas the BTT group increased by 4.6%. Likewise, the BPT group
      demonstrated a significant greater improvement of jump height than BTT group (an
      increase of 15.4% vs. 7.5%, P<0.01; respectively). CONCLUSION: These results
      suggest that both training protocols proposed in this study improved vertical
      jump performance. However, a combination of the two protocols, plyometric
      training and sport-specific-exercises, could be useful to optimize performance by
      an easy transition from controlled a-specific to sport-specific performance
      requirements. In conclusion, BPT is a safe and effective method of achieving a
      favourable neuro-muscular performance than BTT in female basketball players.

PMID- 24921612
TI  - The effect of incline on sprint and bounding performance in cross-country skiers.
AB  - AIM: Aim of the present study was to investigate performance and kinematics of
      cross-country skiers during sprint running and bounding on different inclines, in
      relationship to maximal strength, power and skiing performance. METHODS: On day
      one, the maximal strength of 14 elite skiers was tested using a mid-thigh
      isometric pull and maximal relative leg power determined using squat and
      countermovement jumps. Day two involved 15-m maximal sprints and 5-step bounding
      at 0o, 7.5 degrees  and 15o inclines. From video recordings sprint, step, contact
      and flight times; step length and frequency; total number of sprint steps and
      average bounding velocity were determined. Skiing performance was assessed using
      International Ski Federation (FIS) points from the preceding season and compared
      to strength, power, bounding and sprint performance, and kinematics. RESULTS: On
      steeper inclines sprint time was higher and bounding distance shorter (both
      P<0.001), and step frequency during sprinting and bounding, reduced and increased
      respectively (P<0.001). Isometric maximal strength correlated strongly with
      bounding distance on the two steeper inclines (r=0.76 and 0.83). Squat and
      countermovement jump heights correlated moderately with sprint performance at
      both 7 degrees  and 15 degrees , and bounding performance on all three inclines
      (r=0.55-0.65). The distance bounded uphill correlated moderately with FIS points
      (r=-0.55 and -0.67). CONCLUSION: Incline influenced sprinting and bounding
      performance and kinematics. Maximal leg power is important for both sprinting and
      bounding uphill, while maximal strength is important for the latter. The skiers
      with better FIS rankings bounded farther on steeper inclines, suggesting that
      this capacity is beneficial for cross-country skiing performance.

PMID- 24921613
TI  - Effects of an acute high-intensity interval training protocol on plasma
      viscosity.
AB  - AIM: High-intensity interval training (HIT) is an exercise model that has been
      seen to cause similar muscle adaptations and improvements in exercise performance
      to other traditional exercise models. This study aimed to examine the effects of
      low-volume HIT exercise on plasma viscosity (PV). METHODS: Ten healthy male
      subjects (25.80+/-3.39 years) randomly performed a HIT running protocol (2-min
      warm up at 8 km/h, 5x2-min bouts at 90% maximal heart rate, separated by 2-min at
      8 km/h, finished with another 2-min period at 8 km/h) or an aerobic (AER) running
      exercise (60'at 55% VO2max). Blood samples were drawn before and after exercise,
      and after 30-minute recovery. PV, hematocrit (Hct), fibrinogen, total proteins,
      triglycerides, total-cholesterol and glucose levels were analyzed. Plasma volume
      loss during exercise was calculated. RESULTS: PV rose after HIT (P<0.05) while
      Hct rose after both protocols. Plasma volume loss was higher after HIT (-6.35+/
      3.47%) than after AER (-3.11+/-2.49%) (P=0.045). Total-proteins (P<0.001),
      triglycerides (P=0.013), total-cholesterol (P<0.001) and glucose (P=0.001)
      concentrations increased after HIT. After AER no statistically significant
      differences were found in plasma constituents concentrations. CONCLUSION: A low
      volume HIT session causes a sufficient loss in plasma volume that leads to
      significantly incremented plasma constituents' concentrations and, therefore, a
      mild transient rise in PV.

PMID- 24921614
TI  - High frequency performance analysis of professional soccer goalkeepers: a pilot
      study.
AB  - AIM: High-speed video analysis was performed during ten official-matches, to
      assess the performance of ten goalkeepers (GK) from Italian third/fourth
      divisions (C-D). METHODS: The variables studied were: number (N.) of frontal and
      lateral actions with distance covered (speed during first-last meter) and total
      distance covered during match. RESULTS: Match analysis showed that N. of lateral
      (right/left) changes of direction in GK-C was 48% (P<0.005) lower, and forward
      changes of action 53% greater (P<0.001) compared to GK-D. N. of forward and
      lateral actions in GK-C was 49% and 67% (P<0.001 and P<0.0001) greater than GK-D,
      respectively. Particularly, in GK-C the covered average distance, frontal and
      lateral, was 27% and 58% (P<0.005 and P<0.001) greater than in GK-D,
      respectively. Velocity of first meter of forward and lateral actions for GK-C
      were 9% and 27% lower (P>0.05 and P>0.05) than GK-D, respectively. Last meter of
      forward and lateral actions for GK-C was 57% greater and 43% lower (P<0.001 and
      P<0.005) than GK-D, respectively. Finally, total covered distance, considering
      all actions, was 60% greater for GK-C compared to GK-D (P<0.001). CONCLUSION: The
      work presented in this paper identifies the relevant aspects of the goalkeeper
      game that are valuable for a coach in terms of team and individual performance
      analysis.

PMID- 24921615
TI  - IPAQ interview version: convergent validity with accelerometers and comparison of
      physical activity and sedentary time levels with the self-administered version.
AB  - AIM: This study aimed to assess convergent validity of International Physical
      Activity Questionnaire (IPAQ) interview (long form, last seven days), and to
      examine differences in reported physical activity and sedentary time between the
      self-administered and interview versions of the long IPAQ (last seven days); and
      whether these differences depend on gender, age, educational level and weight
      status. METHODS: In total, 542 Belgian adults (45.3% male, 43.8+/-12.1 years)
      completed the IPAQ self-administered version. Data of these adults were compared
      with data of 542 adults (45.2% male, 43.5+/-12.3 years) who completed the IPAQ
      interview version and wore an accelerometer for seven consecutive days. Samples
      were matched on gender, age, education, neighborhood characteristics and time of
      data collection. RESULTS: Convergent validity of the IPAQ interview version was
      moderate for total physical activity (Spearman rho=0.37, P<0.001) and high for
      sedentary time (Spearman rho=0.67; P<0.001). Bland-Altman plots showed that
      systematic and proportional biases were present for total physical activity; for
      sedentary time only systematic bias was present. Adults who completed the self
      administered IPAQ reported higher means for most types of physical activity and
      less sedentary time than those who completed the IPAQ interview version.
      Differences between the two IPAQ versions were larger in males, lower-educated,
      older and overweight/obese adults. CONCLUSION: Convergent validity of assessing
      total physical activity using IPAQ interview was similar to previous studies
      examining validity of the IPAQ, but stronger results were found for sedentary
      time. In general, and especially in males, lower-educated, older and
      overweight/obese adults, the use of the IPAQ interview version assessed by
      trained researchers, should be recommended to collect self-reported data on
      physical activity and sedentary time.

PMID- 24921616
TI  - Unknown loads affect force production capacity in early phases of bench press
      throws.
AB  - AIM: Explosive strength training aims to improve force generation in early phases
      of movement due to its importance in sport performance. The present study
      examined the influence of lack of knowledge about the load lifted in explosive
      parameters during bench press throws. METHODS: Thirteen healthy young men (22.8+/
      2.0 years) participated in the study. Participants performed bench press throws
      with three different loads (30, 50 and 70% of 1 repetition maximum) in two
      different conditions (known and unknown loads). In unknown condition, loads were
      changed within sets in each repetition and participants did not know the load,
      whereas in known condition the load did not change within sets and participants
      had knowledge about the load lifted. RESULTS: Results of repeated-measures ANOVA
      revealed that unknown conditions involves higher power in the first 30, 50, 100
      and 150 ms with the three loads, higher values of ratio of force development in
      those first instants, and differences in time to reach maximal rate of force
      development with 50 and 70% of 1 repetition maximum. CONCLUSION: This study
      showed that unknown conditions elicit higher values of explosive parameters in
      early phases of bench press throws, thereby this kind of methodology could be
      considered in explosive strength training.

PMID- 24921617
TI  - Effects of mini trampoline exercise on male gymnasts' physiological parameters: a
      pilot study.
AB  - AIM: There are limited studies that indicate the effects of trampoline exercise
      on strength and other physiological parameters. This study aims to determine
      whether twelve weeks of trampoline exercise would have any effects on the
      physical and physiological parameters of male gymnasts. METHODS: A number of 20
      intercollegiate competitive male gymnasts (as experimental group) and 20 non
      athlete male (as control group) participated voluntarily. Their anthropometric
      characteristics and the anaerobic power were measured and their back strength,
      vertical jump, standing long jump and 20 meter sprint performances were measured.
      RESULTS: As a result; whereas 12 weeks of trampoline exercise improved standing
      long jump (before 242.35+/-3.40 cm; after 251.70+/-2.95 cm) and also vertical
      jump, 20 meter sprint speed and anaerobic power of subjects. We did not observe
      significant changes on back strength performances (before 148.32+/-5.73 kg; after
      148.10+/-5.71). CONCLUSION: The trampoline exercise protocol improved
      significantly speed, jump and anaerobic performances of the experimental group,
      while did not induced any changes on back strength performances. More studies are
      necessary to confirm the interesting results coming from this pilot intervention.

PMID- 24921618
TI  - The role of exercise in migraine treatment.
AB  - This review aims to provide a comprehensive overview of the literature on the use
      of exercise for migraine treatment with regard to its efficacy, mechanism of
      action and role in practice. Many randomized studies have reported the efficacy
      of prophylactic treatment of migrane with medications such as beta blockers or
      antiepileptic drugs. Studies on alternative approaches, like aerobic exercise and
      biofeedback, are however limited but also considered to be effective. Scientific
      databases were searched with keywords "exercise" and "migraine". The resulting
      publications were gathered, examined and discussed throughly. Past studies had
      limitations and were few in number, but more recent randomized controlled studies
      have concretely provided level of evidence about the effectiveness of exercise in
      prophylactic treatment of migraine. Core properties of exercise like intensity,
      duration, frequency, type and warming up period are required to be monitored
      while treating migraine to increase the beneficial effects and, also to prevent
      injuries and side effects which may include exertional headache. Isometric neck
      exercise is helpful when the migraine is accompanied by neck pain. Patient
      population with low beta endorphin level in blood, high physical fitness and high
      motivation receives significant benefits from the exercise treatment. The action
      of exercise on migraine is in general related to neurochemical factors,
      psychological states and increase in cardivascular and cerebrovascular fitness.
      Considering its effectiveness and minimal side effects, migraine patients should
      often be encouraged to practice physical exercise with intensity, frequency and
      duration that should be carefully instituted to achieve the most beneficial
      outcome while preventing potential injuries and side effects. 

PMID- 24921619
TI  - Mean power during 20 sec all-out test to predict 2000 m rowing ergometer
      performance in national level young rowers.
AB  - AIM: The aim of this study was to assess the relationship between mean power
      during 20 s all-out rowing ergometer test and 2000 m rowing ergometer
      performance, in 20 young male rowers (mean age 15.2+/-1.3 years). METHODS: Mean
      power during 20 s all-out test (W20), maximal oxygen uptake during incremental
      test (VO2max), and anthropometric values, were measured and correlated with the
      time to perform a 2000 m trial (t2000). RESULTS: W20 showed the highest
      correlation with t2000 (r=-0.947, P<0.0001). Stepwise multiple linear regression
      analysis showed that W20, VO2max, and fat-free mass, were the variables most
      correlated with t2000, accounting for 95.1% of the variance, and that 89.7% of
      the variance in 2000 m rowing ergometer performance time was accounted for by
      W20. CONCLUSION: These results suggest that W20 is an important predictor of 2000
      m rowing ergometer performance, and the 20 s all-out test on rowing ergometer may
      be a useful monitoring tool for young rowers.

PMID- 24921620
TI  - Benefits of Zumba Fitness(r) among sedentary adults with components of the
      metabolic syndrome: a pilot study.
AB  - AIM: The aim of this study was to assess the feasibility of a 12 week Zumba
      Fitness(r) pilot study and temporal changes in components of the metabolic
      syndrome (MetS) among sedentary, obese women with at least two MetS components.
      METHODS: Participants attended Zumba Fitness(r) classes twice a week for 12
      weeks. Feasibility was measured by recruitment rates, subject retention, and
      adherence. Anthropometric measures, blood pressure and fasting glucose,
      triglycerides and HDL-cholesterol were measured at baseline and after the 12 week
      intervention. RESULTS: Among the 13 female participants, mean age was 52.5
      (SD:10.6) years, 77% were ethnic minorities, mean BMI was 34.5 kg/m2 (SD:4.9) and
      69.2% met the MetS criteria. Among 35 adults who completed the telephone
      eligibility screening, 23 (66%) were eligible for a clinic screening visit, 18 of
      whom met eligibility criteria, 16 (89%) initiated Zumba classes, and 13 (81%)
      completed the pilot study. Mean attendance was 17 classes, comprising 71% of the
      total 24 classes. Weight reduced non-significantly by 0.96 kg (P=0.87) while
      systolic and diastolic blood pressure decreased by 13.63 (P=0.028) and 6.19 mmHg
      (P=0.03), respectively with no change in anti-hypertensive medication use.
      Fasting triglycerides decreased by 16.92 mg/dL (P=0.025) with no participants
      taking niacin or fibrates prior to or during the study. Mean HDL-cholesterol
      decreased (by 2.85 mg/dL) and fasting glucose increased slightly (by 1.62 mg/dL),
      but not significantly. CONCLUSION: This twelve week Zumba Fitness(r) intervention
      showed good feasibility and adherence, with significant reductions in blood
      pressure and triglyceride levels, despite minimal weight loss.

PMID- 24921621
TI  - Effect of colored lenses on muscular performance.
AB  - AIM: The effect of color on physiological parameters appears well documented.
      However, methodological weaknesses and limitations to practical application
      suggest it to be substantially under researched with regard to physical
      performance. The aim of this study was to consider the effects of red, blue and
      clear (control) colored lens glasses on a muscular endurance task. METHODS:
      Fifteen healthy males (21+/-1.34 years) were instructed to perform repetitions to
      failure using their predetermined 25 repetition maximum (RM) on a seated leg
      press. Participants completed three randomised trials exposed to blue, red and
      clear lenses. RESULTS: A repeated measure ANOVA identified a significant
      difference in the amount of repetitions performed between the three conditions. A
      pairwise comparison revealed significantly greater repetitions for the blue lens
      condition compared to clear lenses (P=0.008). From the data an effect size (ES)
      of 0.76 was calculated for blue lensed glasses. The red lens condition showed no
      significant variation from clear lenses in repetitions performed. CONCLUSION: The
      findings of this research suggest that exposure to the color blue improves
      performance of a muscular endurance based task. Such a simple and inexpensive
      performance enhancement warrants further investigation to explore different
      exercise modalities as well as effects of different colored lenses, and the
      mechanisms as to how color affects performance.

PMID- 24921622
TI  - The evaluation of BMI and serum beta-endorphin levels: the study of acute
      exercise intervention.
AB  - AIM: The aim of this study was to compare BMI and the effects of a session of
      acute exercise on serum beta-endorphin levels among the sprint swimmers and
      runners. METHODS: In a semi-experimental study, 15 healthy skilled male swimmers
      (mean and SD of age: 21.64 +/- 2.35, weight: 75.25 +/- 9.81 kg, height: 180.31 +/
      4.75 cm), and 14 healthy skilled runners (age: 21.38 +/- 2.76, weight: 69.78 +/-
      6.86 kg, height: 182.21 +/- 5.22 cm), purposefully and voluntarily participated
      in this study. Venous blood samples of the subjects were taken in three stages 1)
      basic conditions; 2) immediately after each field of specialized training, with
      an intensity equal to 80-85% VO(2max) 30 minutes after exercise in the fasting
      state. Data was analyzed using with repeated measures (ANOVA). RESULTS: The body
      composition and anthropometric variables assessed in the study were not
      significantly different between the 2 groups, except BMI, which was significant
      (P<0.05). The baseline beta-endorphin serum levels were significantly higher in
      swimmers than runners (P=0.009). There were significant differences between
      levels of beta-endorphin of male sprint runners and swimmers in the three periods
      before, immediately after and 30 minutes after exercise (P <= 0. 05). CONCLUSION:
      The results showed that Increased fat storage may underlie the higher BMI
      observed in swimmers compared to runners and B-Endorphin Serum Levels was in
      swimmers more than runners and an acute exercise session significantly increases
      the levels of beta-endorphin serum hormone in sprint swimmers and runners.

PMID- 24921623
TI  - The effect of spinach supplementation on exercise-induced oxidative stress.
AB  - AIM: Nutritional supplements have been very popular among athletes and
      individuals. Spinach is an important dietary vegetable rich in antioxidants which
      is commonly consumed. This study was conducted to assess the effects of chronic
      daily spinach supplementation on known markers of oxidative stress and muscle
      damage following half-marathon in well-trained healthy young men. METHODS: Twenty
      well-trained men volunteered for this study. Participants were randomized in an
      open study placebo-controlled fashion into two groups: Spinach (S) (N.=10) and
      placebo (P) (N.=10). The participants took spinach supplementation or placebo
      daily for 14 days before running. Participants ran 21.1 km. The spinach
      supplementation was prepared at 1 g/kg body weight. Total antioxidant capacity
      (TAC) was determined as marker of plasma antioxidant capacity. Creatine kinase
      (CK) was measured as marker of muscle damage and malondialdehyde (MDA), protein
      carbonyl (PC) and uric acid were measured as markers of oxidative stress.
      RESULTS: TAC significantly elevated after supplementation in S group (P<0.05).
      Acute exercise led to elevated levels of serum MDA, PC and CK (P<0.05). Spinach
      supplementation maintained PC, MDA, uric acid and CK at lower levels after
      exercise than the placebo (P<0.05). CONCLUSION: These results suggest that
      chronic daily oral supplementation of spinach has alleviating effects on known
      markers of oxidative stress and muscle damage following a half-marathon in well
      trained healthy young men.

PMID- 24921624
TI  - High rates of complications following Kingella kingae infective endocarditis in
      children: a case series and review of the literature.
AB  - Kingella kingae is part of the Haemophilus spp., Aggregatibacter spp.,
      Cardiobacterium hominis, Eikenella corrodens and Kingella spp. organisms that are
      known to cause bacterial endocarditis. Evidence suggests it is also a common
      pharyngeal colonizer in children <2 years of age. We reviewed the literature to
      determine common complications of K. kingae infective endocarditis in children. 

PMID- 24921625
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Costa
      Rican children.
AB  - We collected all Staphylococcus aureus isolates from the National Children's
      Hospital in Costa Rica to evaluate the prevalence and molecular epidemiology of
      methicillin-resistant Staphylococcus aureus (MRSA). Of 299 S. aureus isolates,
      61% were MRSA. Most MRSA isolates (94.5%) carried SCCmec IV, and 45.6% carried
      Panton-Valentine leukocidin-encoding genes. The high prevalence of MRSA in this
      population highlights the need for improvement of antibiotic prescription and
      infection control measures. 

PMID- 24921626
TI  - The largest Silurian vertebrate and its palaeoecological implications.
AB  - An apparent absence of Silurian fishes more than half-a-metre in length has been
      viewed as evidence that gnathostomes were restricted in size and diversity prior
      to the Devonian. Here we describe the largest pre-Devonian vertebrate (Megamastax
      amblyodus gen. et sp. nov.), a predatory marine osteichthyan from the Silurian
      Kuanti Formation (late Ludlow, ~423 million years ago) of Yunnan, China, with an
      estimated length of about 1 meter. The unusual dentition of the new form suggests
      a durophagous diet which, combined with its large size, indicates a considerable
      degree of trophic specialisation among early osteichthyans. The lack of large
      Silurian vertebrates has recently been used as constraint in palaeoatmospheric
      modelling, with purported lower oxygen levels imposing a physiological size
      limit. Regardless of the exact causal relationship between oxygen availability
      and evolutionary success, this finding refutes the assumption that pre-Emsian
      vertebrates were restricted to small body sizes. 

PMID- 24921627
TI  - High prevalence and spatial distribution of Strongyloides stercoralis in rural
      Cambodia.
AB  - BACKGROUND: The threadworm, Strongyloides stercoralis, endemic in tropical and
      temperate climates, is a neglected tropical disease. Its diagnosis requires
      specific methods, and accurate information on its geographic distribution and
      global burden are lacking. We predicted prevalence, using Bayesian geostatistical
      modeling, and determined risk factors in northern Cambodia. METHODS: From
      February to June 2010, we performed a cross-sectional study among 2,396
      participants from 60 villages in Preah Vihear Province, northern Cambodia. Two
      stool specimens per participant were examined using Koga agar plate culture and
      the Baermann method for detecting S. stercoralis infection. Environmental data
      was linked to parasitological and questionnaire data by location. Bayesian mixed
      logistic models were used to explore the spatial correlation of S. stercoralis
      infection risk. Bayesian Kriging was employed to predict risk at non-surveyed
      locations. PRINCIPAL FINDINGS: Of the 2,396 participants, 44.7% were infected
      with S. stercoralis. Of 1,071 strongyloidiasis cases, 339 (31.6%) were among
      schoolchildren and 425 (39.7%) were found in individuals under 16 years. The
      incidence of S. stercoralis infection statistically increased with age. Infection
      among male participants was significantly higher than among females (OR: 1.7; 95%
      CI: 1.4-2.0; P<0.001). Participants who defecated in latrines were infected
      significantly less than those who did not (OR: 0.6; 95% CI: 0.4-0.8; P=0.001).
      Strongyloidiasis cases would be reduced by 39% if all participants defecated in
      latrines. Incidence of S. stercoralis infections did not show a strong tendency
      toward spatial clustering in this province. The risk of infection significantly
      decreased with increasing rainfall and soil organic carbon content, and increased
      in areas with rice fields. CONCLUSIONS/SIGNIFICANCE: Prevalence of S. stercoralis
      in rural Cambodia is very high and school-aged children and adults over 45 years
      were the most at risk for infection. Lack of access to adequate treatment for
      chronic uncomplicated strongyloidiasis is an urgent issue in Cambodia. We would
      expect to see similar prevalence rates elsewhere in Southeast Asia and other
      tropical resource poor countries.

PMID- 24921628
TI  - Improving Performance During Image-Guided Procedures.
AB  - OBJECTIVE: Image-guided procedures have become a mainstay of modern health care.
      This article reviews how human operators process imaging data and use it to plan
      procedures and make intraprocedural decisions. METHODS: A series of models from
      human factors research, communication theory, and organizational learning were
      applied to the human-machine interface that occupies the center stage during
      image-guided procedures. RESULTS: Together, these models suggest several
      opportunities for improving performance as follows: 1. Performance will depend
      not only on the operator's skill but also on the knowledge embedded in the
      imaging technology, available tools, and existing protocols. 2. Voluntary
      movements consist of planning and execution phases. Performance subscores should
      be developed that assess quality and efficiency during each phase. For procedures
      involving ionizing radiation (fluoroscopy and computed tomography), radiation
      metrics can be used to assess performance. 3. At a basic level, these procedures
      consist of advancing a tool to a specific location within a patient and using the
      tool. Paradigms from mapping and navigation should be applied to image-guided
      procedures. 4. Recording the content of the imaging system allows one to
      reconstruct the stimulus/response cycles that occur during image-guided
      procedures. CONCLUSIONS: When compared with traditional "open" procedures, the
      technology used during image-guided procedures places an imaging system and long
      thin tools between the operator and the patient. Taking a step back and
      reexamining how information flows through an imaging system and how actions are
      conveyed through human-machine interfaces suggest that much can be learned from
      studying system failures. In the same way that flight data recorders
      revolutionized accident investigations in aviation, much could be learned from
      recording video data during image-guided procedures.

PMID- 24921629
TI  - Comparative analysis of human tissue interactomes reveals factors leading to
      tissue-specific manifestation of hereditary diseases.
AB  - An open question in human genetics is what underlies the tissue-specific
      manifestation of hereditary diseases, which are caused by genomic aberrations
      that are present in cells across the human body. Here we analyzed this phenomenon
      for over 300 hereditary diseases by using comparative network analysis. We
      created an extensive resource of protein expression and interactions in 16 main
      human tissues, by integrating recent data of gene and protein expression across
      tissues with data of protein-protein interactions (PPIs). The resulting tissue
      interaction networks (interactomes) shared a large fraction of their proteins and
      PPIs, and only a small fraction of them were tissue-specific. Applying this
      resource to hereditary diseases, we first show that most of the disease-causing
      genes are widely expressed across tissues, yet, enigmatically, cause disease
      phenotypes in few tissues only. Upon testing for factors that could lead to
      tissue-specific vulnerability, we find that disease-causing genes tend to have
      elevated transcript levels and increased number of tissue-specific PPIs in their
      disease tissues compared to unaffected tissues. We demonstrate through several
      examples that these tissue-specific PPIs can highlight disease mechanisms, and
      thus, owing to their small number, provide a powerful filter for interrogating
      disease etiologies. As two thirds of the hereditary diseases are associated with
      these factors, comparative tissue analysis offers a meaningful and efficient
      framework for enhancing the understanding of the molecular basis of hereditary
      diseases. 

PMID- 24921630
TI  - The importance of helix P1 stability for structural pre-organization and ligand
      binding affinity of the adenine riboswitch aptamer domain.
AB  - We report here an in-depth characterization of the aptamer domain of the
      transcriptional adenine-sensing riboswitch (pbuE) by NMR and fluorescence
      spectroscopy. By NMR studies, the structure of two aptamer sequences with
      different lengths of the helix P1, the central element involved in riboswitch
      conformational switching, was characterized. Hydrogen-bond interactions could be
      mapped at nucleotide resolution providing information about secondary and
      tertiary structure, structure homogeneity and dynamics. Our study reveals that
      the elongation of helix P1 has pronounced effects not only on the local but on
      the global structure of the apo aptamer domain. The structural differences
      induced by stabilizing helix P1 were found to be linked to changes of the ligand
      binding affinity as revealed from analysis of kinetic and thermodynamic data
      obtained from stopped-flow fluorescence studies. The results provide new insight
      into the sequence-dependent fine tuning of the structure and function of purine
      sensing riboswitches. 

PMID- 24921631
TI  - Amlodipine protects rat ventricular cardiomyoblast H9c2 From hypoxia-induced
      apoptosis and restores oxidative balance by Akt-1-dependent manner.
AB  - BACKGROUND: Hypoxia-induced rise in intracellular calcium concentration is a
      causative agent of apoptosis and oxidative damage in cardiomyocytes. We examined
      the efficacy of calcium channel blocker amlodipine in preventing hypoxia-induced
      apoptosis in H9c2 cells and restoring oxidative balance. METHODS: H9c2 cells were
      exposed to hypoxia (0.5% oxygen) to evaluate the efficacy of amlodipine in
      restoring cellular calcium levels. Cellular markers of apoptosis (Bax/Bcl2 and
      caspase-3, -7, and -9) and pro-survival markers (Akt/p-Akt levels) were evaluated
      under hypoxia. Redox damage was evaluated by assessing markers of oxidative
      damage, that is, glutathione reduced, glutathione oxidized, lipid peroxidation,
      reactive oxygen species, and manganese superoxide dismutase activity. Cellular
      adenosine triphosphate (ATP) pool and AMPKalpha levels were measured to evaluate
      regulation of metabolism under hypoxia. RESULTS: Amlodipine treatment at 25 nM
      prevented apoptosis and restored cellular calcium levels and oxidative damage in
      cardiomyocytes. Stabilization of caspase-3, -7, and -9 along with restoration of
      Akt/p-Akt levels depicted pro-survival efficacy of amlodipine. Also, restoration
      of cellular ATP and AMPKalpha levels indicates that amlodipine prevents
      cardiomyocytes from hypoxia-induced metabolic stress. CONCLUSIONS: Amlodipine
      thus protects H9c2 cells from hypoxia-induced apoptosis by regulating Akt/p-Akt
      mediated caspase-3, -7, and -9 activation and restoring cellular ATP and redox
      status.

PMID- 24921632
TI  - Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage
      dependent calcium channels.
AB  - Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to
      alleviate diseases including hypertension. Eugenol has been demonstrated to relax
      conduit and ear arteries and reduce systemic blood pressure, but mechanisms
      involved are unclear. Here, we studied eugenol regulation of resistance-size
      cerebral arteries that control regional brain blood pressure and flow and
      investigated mechanisms involved. We demonstrate that eugenol dilates arteries
      constricted by either pressure or membrane depolarization (60 mM K) in a
      concentration-dependent manner. Experiments performed using patch-clamp
      electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium
      (Ca) currents, when using Ba as a charge carrier, in isolated cerebral artery
      smooth muscle cells. Eugenol inhibition of voltage-dependent Ca currents involved
      pore block, a hyperpolarizing shift (~-10 mV) in voltage-dependent inactivation,
      an increase in the proportion of steady-state inactivating current, and
      acceleration of inactivation rate. In summary, our data indicate that eugenol
      dilates cerebral arteries by means of multimodal inhibition of voltage-dependent
      Ca channels.

PMID- 24921633
TI  - Balancing Hope and Realism in Family-Centered Care: Physical Therapists' Dilemmas
      in Negotiating Walking Goals with Parents of Children with Cerebral Palsy.
AB  - ABSTRACT The aims of this study were to explore physical therapists' beliefs
      about the value of walking for children with cerebral palsy (CP), how these
      beliefs inform therapy choices, and to describe how physical therapists engage
      families in decision-making regarding walking goals. Eight physical therapists
      who had experience working with children with CP each participated in a
      qualitative, one-to-one interview exploring their walking-related values,
      beliefs, and decision-making practices. The physical therapists' accounts
      demonstrated that they balanced their beliefs and professional expertise with
      families' goals in order to preserve families' hopes and maintain rapport, while
      also ensuring evidence-based and efficacious treatment plans were implemented.
      Participants experienced internal conflict when attempting to balance the
      principles of family-centered care with their personal beliefs and expertise.
      Further research will augment these findings and contribute to ongoing debates
      regarding rehabilitation best practices and family-centered care.

PMID- 24921635
TI  - Risk of secondary malignancy (including breast) in patients with mismatch-repair
      protein deficiency.
AB  - Lynch syndrome (LS) is an autosomal dominant inherited disease that is associated
      with an increased risk for colorectal and endometrial cancer due to germline
      mutations in mismatch-repair (MMR) genes. Whereas primary tumors in this syndrome
      are widely recognized, the relative risk(s) of secondary malignancies,
      particularly breast cancer, in LS patients are still poorly characterized. To
      provide an improved assessment of these risks, MMR status was evaluated in
      secondary tumors from a series of patients with index tumors of known MMR status
      (both proficient and deficient). A total of 1252 tumors (index tumors) and all
      secondary malignancies were tested for MMR by immunohistochemistry (MSH2, MSH6,
      MLH1, PMS2) between 1992 and 2013. Tumors with MLH1/PMS2 deficiency were tested
      for hypermethylation or BRAF mutation, when appropriate. Of the 1252 index
      tumors, 162 were MMR deficient (dMMR), and, of that subset, 32 secondary tumors
      were identified (19.7%). In contrast, 80 secondary tumors were identified in the
      proficient (intact) group (7.3%). Although secondary malignancies were more
      common in the dMMR group (P=0.0001), there was no trend in tumor type.
      Specifically, breast cancer was not overly represented in the dMMR group. When
      secondary tumors had dMMR, they were more likely to have deficiency in MSH2/MSH6
      than in MLH1/PMS2 (P=0.01). Of the patients with tumors exhibiting dMMR, women
      were more likely to have a dMMR secondary tumor in this series (P=0.0001);
      however, breast cancer was not overly represented, and our study provides no
      evidence that it is more frequent in LS. MSH2/MSH6 deficiency is more commonly
      associated with a secondary tumor compared with MLH1/PMS2 deficiency, when
      methylation/BRAF status is taken into account. 

PMID- 24921634
TI  - Imatinib treatment causes substantial transcriptional changes in adult
      Schistosoma mansoni in vitro exhibiting pleiotropic effects.
AB  - BACKGROUND: Schistosome parasites cause schistosomiasis, one of the most
      important infectious diseases worldwide. For decades Praziquantel (PZQ) is the
      only drug widely used for controlling schistosomiasis. The absence of a vaccine
      and fear of PZQ resistance have motivated the search for alternatives. Studies on
      protein kinases (PKs) demonstrated their importance for diverse physiological
      processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and
      SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the
      gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl
      TK inhibitor used in human cancer therapy (Gleevec/Glivec). Imatinib exhibited
      dramatic effects on the morphology and physiology of adult schistosomes in vitro
      causing the death of the parasites. METHODOLOGY/PRINCIPAL FINDINGS: Here we show
      modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical
      assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray
      analyses and qRT-PCR experiments were done to unravel transcriptional processes
      influenced by Imatinib in adult schistosomes in vitro demonstrating a wide
      influence on worm physiology. Surface-, muscle-, gut and gonad-associated
      processes were affected as evidenced by the differential transcription of e.g.
      the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and
      cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated
      genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of
      signaling genes including a ribosomal protein S6 kinase and a glutamate receptor.
      Finally, a comparative in silico analysis of the obtained microarray data sets
      and previous data analyzing the effect of a TGFbetaR1 inhibitor on transcription
      provided first evidence for an association of TGFbeta and Abl kinase signaling.
      Among others GCP and egg formation-associated genes were identified as common
      targets. CONCLUSIONS/SIGNIFICANCE: The data affirm broad negative effects of
      Imatinib on worm physiology substantiating the role of PKs as interesting
      targets.

PMID- 24921636
TI  - Colesevelam and colestipol: novel medication resins in the gastrointestinal
      tract.
AB  - We report the morphologic description of the bile acid sequestrants (BAS)
      colesevelam and colestipol, as well as the largest series of cholestyramine.
      Histologically similar medication resins from 4 institutions were prospectively
      collected over 1 year (26 specimens, 15 patients). Comorbidities included
      hyperlipidemia (4/15), hypertension (4/15), inflammatory bowel disease (4/15),
      coronary artery disease (3/15), diarrhea (7/15), hypothyroidism (2/15), and
      ischemic bowel (1/15). Sites of involvement included the esophagus (1/26),
      stomach (1/26), small intestine (1/26), ileocecal valve (1/26), and colorectum
      (22/26). Associated histologic diagnoses included normal (8/26), chronic mucosal
      injury (11/26), acute inflammation (9/26), erosion/ulceration (6/26), and
      cytomegalovirus (2/26). The BAS resins were histologically indistinguishable from
      each other; they were all eosinophilic on hematoxylin and eosin (H&E) and lacked
      internal "fish-scales." To validate these observations, respective medications
      were submitted for histologic processing; the processed medications were
      identical to those in the patient specimens. Rare, irregular "fracture" lines
      presented diagnostic pitfalls by mimicking the true "fish-scales" of Kayexalate
      and sevelamer. Clues to the correct identification of BAS include recognition
      that the "fracture" lines were subtle, irregular, and restricted to large
      fragments or thick sections, likely representing a processing artifact. Moreover,
      Kayexalate is violet on H&E and black on acid fast bacillus, and sevelamer
      characteristically displays a 2-tone color on H&E and is magenta on acid fast
      bacillus. An association with inflammatory injury was seen (15/26). We believe
      that the BAS are innocent bystanders in complicated patients, although we cannot
      exclude their ability to cause mucosal injury in specific settings. 

PMID- 24921637
TI  - A subset of nondescript axillary lymph node inclusions have the immunophenotype
      of endosalpingiosis.
AB  - We report 2 cases of bland, otherwise nondescript axillary lymph node inclusions
      that have the immunophenotype of endosalpingiosis in patients with concurrent
      invasive breast carcinomas. Neither inclusion demonstrated the classic morphology
      of endosalpingiosis with admixed ciliated and secretory cells. Rather, both cases
      were composed of nondescript cuboidal to columnar bland epithelial cells situated
      within the lymph node capsule. Whereas both inclusions labeled diffusely for
      estrogen receptor and lacked evidence of a myoepithelial component, both labeled
      diffusely for PAX8 and WT-1, which distinguished them from their corresponding
      concurrent primary mammary carcinomas. These findings suggest that a subset of
      otherwise nondescript axillary lymph node inclusions represent endosalpingiosis
      and highlight the utility of PAX8 and WT-1 immunohistochemistry in distinguishing
      these from metastatic well-differentiated ductal carcinoma. 

PMID- 24921638
TI  - "Somatic-type" malignancies arising from testicular germ cell tumors: a
      clinicopathologic study of 124 cases with emphasis on glandular tumors supporting
      frequent yolk sac tumor origin.
AB  - Somatic-type malignancies (SMs) in patients with testicular germ cell tumors
      (GCT) are rare and mostly attributed to "transformation" of teratoma, although
      yolk sac tumor (YST) origin has also been proposed. We studied 124 cases of "SM"
      of testicular GCT origin from 106 patients to evaluate their morphology,
      immunohistochemical features (especially the utility of SALL4), and relationship
      to YST. Primitive neuroectodermal and nephroblastomatous tumors were excluded
      because of prior studies. Patients ranged in age from 15 to 68 years (mean, 33
      y). The tumors ranged from 0.7 to 30 cm (mean, 7.6 cm) and involved the
      retroperitoneum (64%), abdomen/pelvis (10%), lung (10%), mediastinum (6%),
      supraclavicular region/neck (4%), testis (4%), and thigh (1%). Most initial
      diagnoses were sarcomas (n=68) or carcinomas (n=51). On review and
      immunohistochemical analysis, 7 of 45 adenocarcinomas were reclassified as
      glandular YSTs (GYST) on the basis of glypican-3 (GPC3) and/or alpha-fetoprotein
      positivity and scant/absent reactivity for EMA and CK7. These occasionally (29%)
      had subnuclear and sometimes supranuclear vacuoles (endometrioid-like), whereas
      adenocarcinomas were more frequently mucinous (17%) or enteric-type (11%) than
      endometrioid-like (9%). Both expressed CDX2 frequently (83% and 63%,
      respectively). MUC protein 2, 4, 5, and 6 expression was more common in
      adenocarcinomas (7% to 36%) than in GYSTs (0% to 20%) but was infrequent. Both
      were often positive for SALL4, BerEP4, and MOC31; all were negative for TTF-1. On
      follow-up (GYST: range, 23 to 169 mo; mean, 81mo; adenocarcinoma: range, 1 to 170
      mo; mean, 55 mo), 50% and 33% of patients with GYST and adenocarcinoma,
      respectively, died of disease. We reclassified 26 of 76 sarcomatoid tumors as
      sarcomatoid YSTs (SYST) on the basis of positive reactivity for both AE1/3 and
      GPC3. These tumors often had spindled and epithelioid cells in a fibromyxoid
      stroma. SYSTs were often (60%) SALL4 positive, whereas sarcomas were all
      negative. On follow-up (SYST: range, 1 to 259 mo; mean, 62 mo; sarcoma: range, 1
      to 327 mo; mean, 70 mo), 50% and 29% of patients with SYST and sarcoma,
      respectively, died of disease, with most mortality occurring in those with high
      grade tumors. We conclude that, on the basis of a panel of immunoreactivities, a
      significant number of "SMs" in testicular GCT patients are more accurately
      classified as either GYSTs or SYSTs. Ambiguous glandular tumors should be
      evaluated for GPC3, alpha-fetoprotein, CK7, and EMA reactivity and sarcomatoid
      ones for GPC3, AE1/3, and SALL4 reactivity. 

PMID- 24921640
TI  - Syphilis presenting as inflammatory tumors of the liver in HIV-positive
      homosexual men.
AB  - Syphilis, a sexually transmitted infection caused by the spirochete Treponema
      pallidum, has seen a resurgence since 2001, particularly in men who have sex with
      men. Syphilis can affect the liver during the secondary stage as syphilitic
      hepatitis and during the tertiary stage as gummas. We describe 3 cases of
      syphilis in human immunodeficiency virus-positive homosexual men that presented
      as hepatic mass lesions clinically suspected of being malignant tumors.
      Histologically, 2 of the 3 cases showed a plump spindle cell proliferation, mixed
      inflammatory infiltrate with numerous neutrophils, and abscesses, whereas the
      third case showed granulomas and pericholangitis/cholangitis. Immunohistochemical
      staining for T. pallidum showed innumerable organisms in 2 of the cases.
      Pathologists must be aware of the possibility of syphilis causing hepatic
      inflammatory masses in human immunodeficiency virus-positive men who have sex
      with men in order to avoid misdiagnosis or delayed treatment. 

PMID- 24921639
TI  - BRAF V600E immunohistochemistry is reliable in primary and metastatic colorectal
      carcinoma regardless of treatment status and shows high intratumoral homogeneity.
AB  - In colorectal carcinoma the evaluation of BRAF mutation status is increasingly
      being performed given its utility as a prognostic and predictive biomarker.
      However, there are conflicting reports of the sensitivity and specificity of BRAF
      V600E immunohistochemistry (IHC), and little is known about its reliability in
      tissues collected from metastatic sites or after chemotherapy, radiation therapy
      and/or targeted therapy. The degree of intratumoral staining heterogeneity is
      also not well established. We performed IHC for BRAF V600E (VE1) on 204 cases of
      colorectal carcinoma including 59 with the BRAF V600E mutation. These included
      primary (n=147) and metastatic/recurrent (n=57) tumors, collected before (n=133)
      or after (n=71) chemotherapy, radiation therapy and/or targeted therapy.
      Evaluation of a test cohort (39 cases) with knowledge of mutation status
      established a specific staining pattern for the mutation: diffuse cytoplasmic
      staining of near-uniform intensity, regardless of strength of staining. Using
      this pattern, pathologists at 3 levels of training independently performed
      blinded evaluation of the remaining cases. BRAF V600E staining was 96.3%
      sensitive and 98.5% specific for the mutation, including both pretreatment and
      posttreatment specimens. Fleiss kappa for interobserver agreement was 0.96.
      Staining of whole sections of the BRAF mutants showed diffuse staining in all
      cases and uniform or near-uniform intensity in 91%. In 20 cases with both
      pretreatment and posttreatment specimens, there was 100% accuracy and agreement
      in staining between samples. We conclude that BRAF V600E IHC is reliable for the
      evaluation of mutational status in colorectal carcinoma regardless of site or
      prior treatment history, and staining shows a high degree of intratumoral
      homogeneity. 

PMID- 24921641
TI  - Primary sclerosing epithelioid fibrosarcoma of bone: analysis of a series.
AB  - Sclerosing epithelioid fibrosarcoma (SEF) is a rare, aggressive malignant
      neoplasm characterized by small nests and linear arrays of epithelioid cells
      embedded in a dense collagenous matrix. Very few primary SEFs of bone have been
      reported. Recognition is critical, as the dense extracellular collagenous matrix
      can be interpreted as osteoid, leading to misdiagnosis as-osteosarcoma. MUC4 and
      SATB2 are 2 recently characterized immunohistochemical markers for SEF and
      osteosarcoma, respectively. In reports to date, osteosarcomas are positive for
      SATB2 and negative for MUC4, whereas soft tissue SEFs have shown the opposite
      immunohistochemical profile (SATB2-/MUC4+). The purpose of this study was to
      characterize the clinicopathologic and immunohistochemical features of 8 primary
      SEFs of bone. The patients presented at a wide range of ages (25 to 73 y; median
      52 y). Tumors mostly involved long bones of the extremities, with 3 cases
      involving the femur, 2 involving the ulna, and 1 involving the humerus. Other
      sites of involvement included the second rib (1) and the C6 vertebra (1). Follow
      up information was available for 7 patients, 3 of whom developed metastases
      within 2 years of diagnosis. The other 4 patients were free of local recurrence
      or metastases at 1, 5, 12, and >84 months of follow-up, respectively.
      Radiographically, the tumors were predominantly lytic and poorly marginated.
      Histologically, 6 tumors showed pure SEF morphology, and 2 showed hybrid SEF/low
      grade fibromyxoid sarcoma morphology. Focal dystrophic mineralization was seen in
      1 case but was limited to areas of necrosis. None of the tumors showed the lace
      like pattern of mineralization typical of osteosarcoma. The majority (6/8) of the
      tumors strongly expressed MUC4. SATB2 was negative in all but 1 case, which
      showed variable weak to moderate staining in ~50% of nuclei. In general, the
      combination of morphology, MUC4 expression, and the absence of SATB2 expression
      was highly useful in arriving at the correct diagnosis. 

PMID- 24921642
TI  - Variable expression of B-cell transcription factors in reactive immunoblastic
      proliferations: a potential mimic of classical Hodgkin lymphoma.
AB  - Reactive immunoblastic proliferations can histologically mimic classical Hodgkin
      lymphoma (CHL), and show diffuse CD30 expression in large cells. The lack of
      expression of CD15 in a subset of CHL further complicates their separation from
      immunoblastic proliferations. Loss of expression of B-cell transcription factors
      is frequently exploited in making a diagnosis of CHL; however, the staining
      patterns of B-cell transcription factors in immunoblastic proliferations have not
      been extensively studied. Thirty-three cases of reactive immunoblastic
      proliferations were evaluated using a panel of immunohistochemistry for CD30,
      CD15, CD20, CD3, kappa, lambda, CD45RB, MUM1, PAX5, OCT2, and BOB.1, as well as
      Epstein-Barr virus (EBV)/EBV-encoded ribonucleic acid in situ hybridization. A
      newly developed dual-color chromogenic in situ hybridization technology for
      detection of kappa/lambda mRNAs was also used. The majority of immunoblasts
      expressed CD30 in 14 of 33 (42%) cases; none expressed CD15. Loss or weak
      expression of at least 1 transcription factor in B immunoblasts, most commonly
      PAX5, was noted in 24 of 29 (83%) cases. A polytypic light chain expression
      pattern was detected by immunohistochemistry in 14 of 22 (63.6%) cases and by
      dual-color chromogenic in situ hybridization in 9 of 10 (90%) cases studied. EBV
      encoded ribonucleic acid was detected in 8 of 33 (24.2%) cases, 5 of which were
      clinically unrelated to infectious mononucleosis. We conclude that B-cell
      transcription factors can show loss or weak expression in a significant
      proportion of reactive immunoblastic proliferations, and, therefore, staining for
      B-cell transcription factors together with CD30 should be interpreted with
      caution before a diagnosis of CHL is made. 

PMID- 24921643
TI  - Immunohistochemical staining characteristics of nephrogenic adenoma using the PIN
      4 cocktail (p63, AMACR, and CK903) and GATA-3.
AB  - Nephrogenic adenoma (NA) is a benign lesion of the urinary tract associated with
      injury to the urothelium. The varied morphologic patterns of NA make it a
      potential diagnostic pitfall, because it can mimic closely prostatic
      adenocarcinoma and urothelial carcinoma. In current practice, an antibody
      cocktail comprising p63, CK903, and AMACR (PIN-4 cocktail) is frequently utilized
      to evaluate foci suspicious for prostatic adenocarcinoma. Although the staining
      characteristics of the individual components of the PIN-4 cocktail have been
      reported for NA, no study has described the expression patterns for NA when the
      stains are applied as a cocktail. GATA-3 is an emerging marker of urothelial
      carcinoma; however, the GATA-3 staining characteristics of NA have yet to be
      described. Sixty-three NA specimens (M:F=36:27, average age=51.4 y) from various
      locations in the urinary tract including urinary bladder (n=40), ureter (n=3),
      and urethra (n=20) were collected from the archives of 2 institutions.
      Immunohistochemical analysis with the PIN-4 cocktail and GATA-3 antibodies was
      performed, and the distribution and intensity of staining was recorded for each
      antibody in each case. PIN-4 cocktail staining revealed AMACR expression in 56%
      of cases, CK903 expression in 97%, and rare p63 positivity (in only 2 cases).
      Only 2 NA cases displayed an overall PIN-4 staining pattern compatible with
      prostate cancer. GATA-3 expression was noted in 40% of NAs. No correlation
      between AMACR, CK903, or GATA-3 positivity and histologic pattern or anatomic
      location was identified. Although heterogenous staining patterns were seen within
      individual cases, use of the PIN-4 cocktail effectively discriminates NA from
      prostate cancer because of the high frequency of coexpression of AMACR and CK903
      within NA. In addition, GATA-3 is not a useful marker in differentiating between
      NA and urothelial carcinoma. 

PMID- 24921644
TI  - Myofibromas with atypical features: expanding the morphologic spectrum of a
      benign entity.
AB  - Typical myofibromas are biphasic tumors composed of a central zone of immature
      spindled to rounded cells arranged in a pericytic pattern and a peripheral zone
      of myoid nodules. Central necrosis is occasionally seen. A small but undefined
      subset of myofibromas displays atypical features that may lead to a misdiagnosis
      of sarcoma. To more completely characterize these tumors and define their
      behavior, we analyzed our experience with myofibromas having 1 or more atypical
      features including hypercellularity, absent or inconspicuous, poorly demarcated
      myoid nodules, infiltrative growth pattern, and perineural invasion. Of 266 cases
      of myofibromas, 24 cases were retrieved on the basis of pathology reports in
      which atypical features were mentioned. The tumors presented in 16 male and 8
      female individuals (mean age 17 y; range, 2 wk to 62 y) as masses of variable
      size (mean 3.0 cm; range, 1.5 to 6.5 cm). Fourteen cases arose on the head and
      neck and 10 cases on the limbs. The referring or suspected diagnosis was sarcoma
      in 8 cases. The tumors were typically more cellular than ordinary myofibroma with
      levels of cellularity similar to that expected in fibrosarcoma (22/24). In
      addition, they displayed inconspicuous, loosely cohesive (22/24) or absent myoid
      nodules (2/24), infiltrating borders (19/24), intravascular growth (5/24), and
      perineural invasion/nerve entrapment (6/24). The mean mitotic rate was 5
      mitoses/10 high-power fields, but no tumor showed significant cytologic atypia.
      The tumors were positive for actins (11/11) and CD34 (2/8). Follow-up in 14
      patients revealed no distant metastases. We conclude that a small subset of
      myofibromas shows atypical features that complicate the diagnosis but do not
      adversely affect outcome. 

PMID- 24921645
TI  - Do "intimal" sarcomas of the heart exist?

PMID- 24921647
TI  - Pain thresholds in women with chronic pelvic pain.
AB  - PURPOSE OF REVIEW: To update on the latest developments in sensory changes of
      female patients with chronic pelvic pain (CPP). CPP is very common, but its
      pathophysiology is still controversial. Evaluation of pain sensitivity in painful
      and nonpainful areas is key to understanding the underlying peripheral vs.
      central contributions to the symptom. This in turn is fundamental to improving
      the treatment strategies. RECENT FINDINGS: We reviewed the experimental studies
      published over the last year on pain thresholds to different stimuli measured at
      both the somatic and visceral level in women with different forms of recurrent or
      CPP. The majority of the studies indicate a pain threshold decrease to most
      stimuli in skin, subcutis and muscle in painful pelvic areas, the site of
      referred pain from pelvic viscera, as well as a decreased pain threshold in most
      viscera (colon and urinary bladder). A significant threshold decrease is also
      found in deep somatic tissues (subcutis and muscle) outside the painful zone in
      the most severe cases, indicating a state of central sensitization. SUMMARY:
      These findings have important implications for clinical practice: pain threshold
      measurement in both painful and nonpainful sites could have important predictive
      value of the clinical evolution and response to therapy of CPP.

PMID- 24921646
TI  - Two separate modules of the conserved regulatory RNA AbcR1 address multiple
      target mRNAs in and outside of the translation initiation region.
AB  - The small RNA AbcR1 regulates the expression of ABC transporters in the plant
      pathogen Agrobacterium tumefaciens, the plant symbiont Sinorhizobium meliloti,
      and the human pathogen Brucella abortus. A combination of proteomic and
      bioinformatic approaches suggested dozens of AbcR1 targets in A. tumefaciens.
      Several of these newly discovered targets are involved in the uptake of amino
      acids, their derivatives, and sugars. Among the latter is the periplasmic sugar
      binding protein ChvE, a component of the virulence signal transduction system. We
      examined 16 targets and their interaction with AbcR1 in close detail. In addition
      to the previously described mRNA interaction site of AbcR1 (M1), the CopraRNA
      program predicted a second functional module (M2) as target-binding site. Both M1
      and M2 contain single-stranded anti-SD motifs. Using mutated AbcR1 variants, we
      systematically tested by band shift experiments, which sRNA region is responsible
      for mRNA binding and gene regulation. On the target site, we find that AbcR1
      interacts with some mRNAs in the translation initiation region and with others
      far into their coding sequence. Our data show that AbcR1 is a versatile master
      regulator of nutrient uptake systems in A. tumefaciens and related bacteria. 

PMID- 24921648
TI  - Core microbial functional activities in ocean environments revealed by global
      metagenomic profiling analyses.
AB  - Metagenomics-based functional profiling analysis is an effective means of gaining
      deeper insight into the composition of marine microbial populations and
      developing a better understanding of the interplay between the functional genome
      content of microbial communities and abiotic factors. Here we present a
      comprehensive analysis of 24 datasets covering surface and depth-related
      environments at 11 sites around the world's oceans. The complete datasets
      comprises approximately 12 million sequences, totaling 5,358 Mb. Based on
      profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core
      set of reference photic and aphotic depth-related COGs, and a collection of COGs
      that are associated with extreme oxygen limitation were defined. Their inferred
      functions were utilized as indicators to characterize the distribution of light-
      and oxygen-related biological activities in marine environments. The results
      reveal that, while light level in the water column is a major determinant of
      phenotypic adaptation in marine microorganisms, oxygen concentration in the
      aphotic zone has a significant impact only in extremely hypoxic waters.
      Phylogenetic profiling of the reference photic/aphotic gene sets revealed a
      greater variety of source organisms in the aphotic zone, although the majority of
      individual photic and aphotic depth-related COGs are assigned to the same taxa
      across the different sites. This increase in phylogenetic and functional
      diversity of the core aphotic related COGs most probably reflects selection for
      the utilization of a broad range of alternate energy sources in the absence of
      light. 

PMID- 24921649
TI  - Augmenting microarray data with literature-based knowledge to enhance gene
      regulatory network inference.
AB  - Gene regulatory networks are a crucial aspect of systems biology in describing
      molecular mechanisms of the cell. Various computational models rely on random
      gene selection to infer such networks from microarray data. While incorporation
      of prior knowledge into data analysis has been deemed important, in practice, it
      has generally been limited to referencing genes in probe sets and using curated
      knowledge bases. We investigate the impact of augmenting microarray data with
      semantic relations automatically extracted from the literature, with the view
      that relations encoding gene/protein interactions eliminate the need for random
      selection of components in non-exhaustive approaches, producing a more accurate
      model of cellular behavior. A genetic algorithm is then used to optimize the
      strength of interactions using microarray data and an artificial neural network
      fitness function. The result is a directed and weighted network providing the
      individual contribution of each gene to its target. For testing, we used invasive
      ductile carcinoma of the breast to query the literature and a microarray set
      containing gene expression changes in these cells over several time points. Our
      model demonstrates significantly better fitness than the state-of-the-art model,
      which relies on an initial random selection of genes. Comparison to the component
      pathways of the KEGG Pathways in Cancer map reveals that the resulting networks
      contain both known and novel relationships. The p53 pathway results were manually
      validated in the literature. 60% of non-KEGG relationships were supported (74%
      for highly weighted interactions). The method was then applied to yeast data and
      our model again outperformed the comparison model. Our results demonstrate the
      advantage of combining gene interactions extracted from the literature in the
      form of semantic relations with microarray analysis in generating contribution
      weighted gene regulatory networks. This methodology can make a significant
      contribution to understanding the complex interactions involved in cellular
      behavior and molecular physiology. 

PMID- 24921650
TI  - Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on
      fat, movement, and hormonal secretions.
AB  - AMP-activated protein kinase (AMPK) is an evolutionarily conserved master
      regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy
      sensor, AMPK activity is responsive to both metabolic inputs, for instance the
      ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two
      genes, aak-1 and aak-2, encode for the catalytic subunit of AMPK in C. elegans.
      Here we show that in C. elegans loss of aak-2 mimics the effects of elevated
      serotonin signaling on fat reduction, slowed movement, and promoting exit from
      dauer arrest. Reconstitution of aak-2 in only the nervous system restored wild
      type fat levels and movement rate to aak-2 mutants and reconstitution in only the
      ASI neurons was sufficient to significantly restore dauer maintenance to the
      mutant animals. As in elevated serotonin signaling, inactivation of AAK-2 in the
      ASI neurons caused enhanced secretion of dense core vesicles from these neurons.
      The ASI neurons are the site of production of the DAF-7 TGF-beta ligand and the
      DAF-28 insulin, both of which are secreted by dense core vesicles and play
      critical roles in whether animals stay in dauer or undergo reproductive
      development. These findings show that elevated levels of serotonin promote
      enhanced secretions of systemic regulators of pro-growth and differentiation
      pathways through inactivation of AAK-2. As such, AMPK is not only a recipient of
      hormonal signals but can also be an upstream regulator. Our data suggest that
      some of the physiological phenotypes previously attributed to peripheral AAK-2
      activity on metabolic targets may instead be due to the role of this kinase in
      neural serotonin signaling. 

PMID- 24921651
TI  - Large conductance Ca2+-activated K+ channel (BKCa) alpha-subunit splice variants
      in resistance arteries from rat cerebral and skeletal muscle vasculature.
AB  - Previous studies report functional differences in large conductance Ca2+
      activated-K+ channels (BKCa) of smooth muscle cells (VSMC) from rat cerebral and
      cremaster muscle resistance arteries. The present studies aimed to determine if
      this complexity in BKCa activity may, in part, be due to splice variants in the
      pore-forming alpha-subunit. BKCa variants in the intracellular C terminus of the
      alpha-subunit, and their relative expression to total alpha-subunit, were
      examined by qPCR. Sequencing of RT-PCR products showed two alpha-subunit
      variants, ZERO and STREX, to be identical in cremaster and cerebral arteries.
      Levels of STREX mRNA expression were, however, significantly higher in cremaster
      VSMCs (28.9+/-4.2% of total alpha-BKCa) compared with cerebral vessels (16.5+/
      0.9%). Further, a low level of BKCa SS4 alpha-subunit variant was seen in
      cerebral arteries, while undetectable in cremaster arteries. Protein
      biotinylation assays, in expression systems and arterial preparations, were used
      to determine whether differences in splice variant mRNA expression affect surface
      membrane/cytosolic location of the channel. In AD-293 and CHO-K1 cells, rat STREX
      was more likely to be located at the plasma membrane compared to ZERO, although
      the great majority of channel protein was in the membrane in both cases. Co
      expression of beta1-BKCa subunit with STREX or ZERO did not influence the
      dominant membrane expression of alpha-BKCa subunits, whereas in the absence of
      alpha-BKCa, a significant proportion of beta1-subunit remained cytosolic.
      Biotinylation assays of cremaster and cerebral arteries showed that differences
      in STREX/ZERO expression do not alter membrane/cytosolic distribution of the
      channel under basal conditions. These data, however, revealed that the amount of
      alpha-BKCa in cerebral arteries is approximately 20X higher than in cremaster
      vessels. Thus, the data support the major functional differences in BKCa activity
      in cremaster, as compared to cerebral VSMCs, being related to total alpha-BKCa
      expression, regardless of differences in splice variant expression. 

PMID- 24921652
TI  - Establishment of highly tumorigenic human colorectal cancer cell line (CR4) with
      properties of putative cancer stem cells.
AB  - BACKGROUND: Colorectal cancer (CRC) has the third highest mortality rates among
      the US population. According to the most recent concept of carcinogenesis, human
      tumors are organized hierarchically, and the top of it is occupied by malignant
      stem cells (cancer stem cells, CSCs, or cancer-initiating cells, CICs), which
      possess unlimited self-renewal and tumor-initiating capacities and high
      resistance to conventional therapies. To reflect the complexity and diversity of
      human tumors and to provide clinically and physiologically relevant cancer
      models, large banks of characterized patient-derived low-passage cell lines, and
      especially CIC-enriched cell lines, are urgently needed. PRINCIPAL FINDINGS: Here
      we report the establishment of a novel CIC-enriched, highly tumorigenic and
      clonogenic colon cancer cell line, CR4, derived from liver metastasis. This
      stable cell line was established by combining 3D culturing and 2D culturing in
      stem cell media, subcloning of cells with particular morphology, co-culture with
      carcinoma associated fibroblasts (CAFs) and serial transplantation to NOD/SCID
      mice. Using RNA-Seq complete transcriptome profiling of the tumorigenic fraction
      of the CR4 cells in comparison to the bulk tumor cells, we have identified about
      360 differentially expressed transcripts, many of which represent stemness,
      pluripotency and resistance to treatment. Majority of the established CR4 cells
      express common markers of stemness, including CD133, CD44, CD166, EpCAM, CD24 and
      Lgr5. Using immunocytochemical, FACS and western blot analyses, we have shown
      that a significant ratio of the CR4 cells express key markers of pluripotency
      markers, including Sox-2, Oct3/4 and c-Myc. Constitutive overactivation of ABC
      transporters and NF-kB and absence of tumor suppressors p53 and p21 may partially
      explain exceptional drug resistance of the CR4 cells. CONCLUSIONS: The highly
      tumorigenic and clonogenic CIC-enriched CR4 cell line may provide an important
      new tool to support the discovery of novel diagnostic and/or prognostic
      biomarkers as well as the development of more effective therapeutic strategies.

PMID- 24921654
TI  - Function and activity in patients with knee arthroplasty: validity and
      reliability of a German version of the Lysholm Score and the Tegner Activity
      Scale.
AB  - OBJECTIVE: The Lysholm score and the Tegner activity scale are widely used for
      assessing knee function and activity level after knee ligament injuries. This
      study aimed to asses validity and reliability of the German versions of the
      Lysholm score (Lysholm-G) and the Tegner activity scale (Tegner-G) in patients
      after total knee arthroplasty (TKA). METHODS: Two patient groups (<3 months
      postoperative; 3 to 12 months postoperative) and a healthy control group
      completed both questionnaires twice within 3 to 7 days. On the first occasion,
      the SF-12 questionnaire was also administered. The instruments' absolute and
      relative reliability, internal consistency, construct validity (discriminative
      validity and exploratory factor analysis), criterion validity, and floor/ceiling
      effects were determined. RESULTS: Both instruments showed acceptable relative
      reliability (Lysholm-G: ICC2,1 = 0.87; Tegner-G: ICC2,1 = 0.79), and the Lysholm
      G had a Cronbach's alpha of 0.93. Kruskal-Wallis test and post-hoc Mann-Whitney U
      tests showed significant differences in both scores among the groups. Factor
      analysis of Lysholm-G yielded three factors that together explained 76% of the
      variance. Correlations between the Lysholm-G/Tegner-G and the physical component
      of the SF-12 were moderate (rho = 0.60/0.59). Item analysis of the Lysholm-G
      revealed a low relative reliability for the item "instability" and low
      discriminative validity for the items "locking" and "instability". CONCLUSIONS:
      This study demonstrated acceptable psychometric performances for the Lysholm-G
      and the Tegner-G scales as outcome measures for patients with TKA. A short
      version of the Lysholm score without the "locking" and "instability" items might
      be more appropriate for TKA patients.

PMID- 24921653
TI  - Differing effects of metformin on glycemic control by race-ethnicity.
AB  - CONTEXT: Metformin is considered first-line treatment for type 2 diabetes
      mellitus. However, little is known about its effects in African American
      individuals. OBJECTIVE: The objective of the study was to assess whether
      metformin's effect on glycemic control differs by race-ethnicity Design:
      Electronic health records were used to identify adults who had a diagnosis of
      diabetes, two or more fills of metformin, and two or more glycated hemoglobin
      (HbA1c) measurements. Pharmacy claims were used to estimate metformin exposure
      based on fill frequency and dose dispensed. Regression analyses modeled the
      relationship between metformin exposure and HbA1c levels. Analyses were
      stratified by race-ethnicity and baseline HbA1c values. SETTING: The study was
      conducted at a large health system in southeast Michigan. MAIN OUTCOME MEASURE:
      Differences in HbA1c levels while on metformin were measured. RESULTS: We
      identified 19 672 patients with diabetes taking metformin; 7429 were African
      American and 8783 were European American. Baseline HbA1c values in these two
      groups were 7.81% (61.8 mmol/mol) and 7.38% (57.1 mmol/mol), respectively.
      Compared with no use, metformin was associated with a 0.62% (6.8 mmol/mol)
      reduction in HbA1c; however, there was a significant difference by race-ethnicity
      (P < .001). Among African American individuals, metformin use was associated with
      a 0.90% (9.8 mmol/mol) reduction in HbA1c levels, whereas among European
      Americans, metformin was associated with a 0.42% (4.6 mmol/mol) reduction.
      Irrespective of baseline HbA1c, metformin use was associated with lower HbA1c
      levels in African American individuals. CONCLUSIONS: African American individuals
      appear to have a better glycemic response to metformin when compared with
      European Americans. Further studies are needed to determine whether this
      translates to commensurate reductions in diabetes complications.

PMID- 24921655
TI  - Fish product mislabelling: failings of traceability in the production chain and
      implications for illegal, unreported and unregulated (IUU) fishing.
AB  - Increasing consumer demand for seafood, combined with concern over the health of
      our oceans, has led to many initiatives aimed at tackling destructive fishing
      practices and promoting the sustainability of fisheries. An important global
      threat to sustainable fisheries is Illegal, Unreported and Unregulated (IUU)
      fishing, and there is now an increased emphasis on the use of trade measures to
      prevent IUU-sourced fish and fish products from entering the international
      market. Initiatives encompass new legislation in the European Union requiring the
      inclusion of species names on catch labels throughout the distribution chain.
      Such certification measures do not, however, guarantee accuracy of species
      designation. Using two DNA-based methods to compare species descriptions with
      molecular ID, we examined 386 samples of white fish, or products labelled as
      primarily containing white fish, from major UK supermarket chains. Species
      specific real-time PCR probes were used for cod (Gadus morhua) and haddock
      (Melanogrammus aeglefinus) to provide a highly sensitive and species-specific
      test for the major species of white fish sold in the UK. Additionally, fish
      specific primers were used to sequence the forensically validated barcoding gene,
      mitochondrial cytochrome oxidase I (COI). Overall levels of congruence between
      product label and genetic species identification were high, with 94.34% of
      samples correctly labelled, though a significant proportion in terms of potential
      volume, were mislabelled. Substitution was usually for a cheaper alternative and,
      in one case, extended to a tropical species. To our knowledge, this is the first
      published study encompassing a large-scale assessment of UK retailers, and if
      representative, indicates a potentially significant incidence of incorrect
      product designation. 

PMID- 24921656
TI  - Identification of miRNAs that specifically target tumor suppressive KLF6-FL
      rather than oncogenic KLF6-SV1 isoform.
AB  - The Kruppel like factor 6 (KLF6) gene encodes multiple protein isoforms derived
      from alternative mRNA splicing, most of which are intimately involved in
      hepatocarcinogenesis and tumor progression. Recent bioinformatics analysis shows
      that alternative mRNA splicing of the KLF6 gene produces around 16 alternatively
      spliced variants with divergent or even opposing functions. Intriguingly, the
      full-length KLF6 (KLF6-FL) is a tumor suppressor gene frequently inactivated in
      liver cancer, whereas KLF6 splice variant 1 (KLF6-SV1) is an oncogenic isoform
      with antagonistic function against KLF6-FL. Compelling evidence indicates that
      miRNA, the small endogenous non-coding RNA (ncRNA), acts as a vital player in
      modulating a variety of cellular biological processes through targeting different
      mRNA regions of protein-coding genes. To identify the potential miRNAs
      specifically targeting KLF6-FL, we utilized bioinformatics analysis in
      combination with the luciferase reporter assays and screened out two miRNAs,
      namely miR-210 and miR-1301, specifically targeted the tumor suppressive KLF6-FL
      rather than the oncogenic KLF6-SV1. Our in vitro experiments demonstrated that
      stable expression of KLF6-FL inhibited cell proliferation, migration and
      angiogenesis while overexpression of miR-1301 promoted cell migration and
      angiogenesis. Further experiments demonstrated that miR-1301 was highly expressed
      in liver cancer cell lines as well as clinical specimens and we also identified
      the potential methylation and histone acetylation for miR-1301 gene. To sum up,
      our findings unveiled a novel molecular mechanism that specific miRNAs promoted
      tumorigenesis by targeting the tumor suppressive isoform KLF6-FL rather than its
      oncogenic isoform KLF6-SV1. 

PMID- 24921657
TI  - An increase in reactive oxygen species by deregulation of ARNT enhances
      chemotherapeutic drug-induced cancer cell death.
AB  - BACKGROUND: Unique characteristics of tumor microenvironments can be used as
      targets of cancer therapy. The aryl hydrocarbon receptor nuclear translocator
      (ARNT) is an important mediator of tumor progression. However, the functional
      role of ARNT in chemotherapeutic drug-treated cancer remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we found that knockdown of ARNT in cancer
      cells reduced the proliferation rate and the transformation ability of those
      cells. Moreover, cisplatin-induced cell apoptosis was enhanced in ARNT-deficient
      cells. Expression of ARNT also decreased in the presence of cisplatin through
      proteasomal degradation pathway. However, ARNT level was maintained in cisplatin
      treated drug-resistant cells, which prevented cell from apoptosis. Interestingly,
      reactive oxygen species (ROS) dramatically increased when ARNT was knocked down
      in cancer cells, enhancing cisplatin-induced apoptosis. ROS promoted cell death
      was inhibited in cells treated with the ROS scavenger, N-acetyl-cysteine (NAC).
      CONCLUSIONS/SIGNIFICANCE: These results suggested that the anticancer activity of
      cisplatin is attributable to its induction of the production of ROS by ARNT
      degradation. Targeting ARNT could be a potential strategy to eliminate drug
      resistance in cancer cells.

PMID- 24921658
TI  - Comparative response of platelet fV and plasma fV to activated protein C and
      relevance to a model of acute traumatic coagulopathy.
AB  - BACKGROUND: Acute traumatic coagulopathy (ATC) has been linked to an increase in
      activated protein C (aPC) from 40 pM in healthy individuals to 175 pM. aPC exerts
      its activity primarily through cleavage of active coagulation factor Va (fVa).
      Platelets reportedly possess fVa which is more resistant to aPC cleavage than
      plasma fVa; this work examines the hypothesis that normal platelets are
      sufficient to maintain coagulation in the presence of elevated aPC. METHODS:
      Coagulation responses of normal plasma, fV deficient plasma (fVdp), and isolated
      normal platelets in fVdp were conducted: prothrombin (PT) tests, turbidimetry,
      and thromboelastography (TEG), including the dose response of aPC on the samples.
      RESULTS: PT and turbidimetric assays demonstrate that normal plasma is resistant
      to aPC at doses much higher than those found in ATC. Additionally, an average
      physiological number of washed normal platelets (200,000 platelets/mm3) was
      sufficient to eliminate the anti-coagulant effects of aPC up to 10 nM, nearly two
      orders of magnitude above the ATC concentration and even the steady-state
      pharmacological concentration of human recombinant aPC, as measured by TEG. aPC
      also demonstrated no significant effect on clot lysis in normal plasma samples
      with or without platelets. CONCLUSIONS: Although platelet fVa shows slightly
      superior resistance to aPC's effects compared to plasma fVa in static models,
      neither fVa is sufficiently cleaved in simulations of ATC or pharmacologically
      delivered aPC to diminish coagulation parameters. aPC is likely a correlative
      indicator of ATC or may play a cooperative role with other activity altering
      products generated in ATC.

PMID- 24921659
TI  - Simplagrin, a platelet aggregation inhibitor from Simulium nigrimanum salivary
      glands specifically binds to the Von Willebrand factor receptor in collagen and
      inhibits carotid thrombus formation in vivo.
AB  - BACKGROUND: Among the several challenges faced by bloodsucking arthropods, the
      vertebrate hemostatic response against blood loss represents an important barrier
      to efficient blood feeding. Here we report the first inhibitor of collagen
      induced platelet aggregation derived from the salivary glands of a black fly
      (Simulium nigrimanum), named Simplagrin. METHODS AND FINDINGS: Simplagrin was
      expressed in mammalian cells and purified by affinity-and size-exclusion
      chromatography. Light-scattering studies showed that Simplagrin has an elongated
      monomeric form with a hydrodynamic radius of 5.6 nm. Simplagrin binds to collagen
      (type I-VI) with high affinity (2-15 nM), and this interaction does not involve
      any significant conformational change as determined by circular dichroism
      spectroscopy. Simplagrin-collagen interaction is both entropically and
      enthalpically driven with a large negative DeltaG, indicating that this
      interaction is favorable and occurs spontaneously. Simplagrin specifically
      inhibits von Willebrand factor interaction with collagen type III and completely
      blocks platelet adhesion to collagen under flow conditions at high shear rates;
      however, Simplagrin failed to block glycoprotein VI and Ialpha2beta1 interaction
      to collagen. Simplagrin binds to RGQOGVMGF peptide with an affinity (K(D) 11 nM)
      similar to that of Simplagrin for collagen. Furthermore, Simplagrin prevents
      laser-induced carotid thrombus formation in vivo without significant bleeding in
      mice and could be useful as an antithrombotic agent in thrombosis related
      disease. CONCLUSION: Our results support the orthology of the Aegyptin clade in
      bloodsucking Nematocera and the hypothesis of a faster evolutionary rate of
      salivary function of proteins from blood feeding arthropods.

PMID- 24921660
TI  - Modulation of chromatin remodelling induced by the freshwater cyanotoxin
      cylindrospermopsin in human intestinal caco-2 cells.
AB  - Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging
      potential public health risk. Although CYN toxicity has been demonstrated, the
      mechanisms involved have not been fully characterised. To identify some key
      pathways related to this toxicity, we studied the transcriptomic profile of human
      intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 uM for
      24hrs) using a non-targeted approach. CYN was shown to modulate different
      biological functions which were related to growth arrest (with down-regulation of
      cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of
      aptx and pms2 genes). Our main results reported an increased expression of some
      histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and
      EHMT2) involved in chromatin remodelling, which is essential for initiating
      transcription. We also detected greater levels of acetylated histone H2A (Lys5)
      and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion,
      CYN overexpressed proteins involved in DNA damage repair and transcription,
      including modifications of nucleosomal histones. Our results highlighted some new
      cell processes induced by CYN. 

PMID- 24921662
TI  - Aggregation effects on the optical emission of 1,1,2,3,4,5-hexaphenylsilole
      (HPS): a QM/MM study.
AB  - We investigate the photophysical property for 1,1,2,3,4,5-hexaphenylsilole (HPS)
      through combined quantum mechanical and molecular mechanical (QM/MM) simulations.
      Under the displaced harmonic oscillator approximation with consideration of the
      Duschinsky rotation effect (DRE), the radiative and nonradiative rates of the
      excited-state decay processes for HPS are calculated by using the analytical
      vibration correlation function approach coupled with first-principles
      calculations. The intermolecular packing effect is incorporated through
      electrostatic interaction modeled by a force field. We find that from the gas
      phase to the solid state (i) the side phenyl ring at the 5-position becomes
      coplanar with the central silacycle, which increases the degree of conjugation,
      thus accelerating the radiative decay process, and (ii) the rotation of the side
      phenyl ring at the 2-position is restricted, which blocks the excited-state
      nonradiative decay channels. Such a synergetic effect largely enhances the solid
      state luminescence quantum efficiency through reducing the nonradiative decay
      rate by about 4 orders of magnitude, leading to the radiative decay overwhelming
      the nonradiatvie decay. In addition, the calculated solid-phase absorption and
      emission optical spectra of HPS are found to be in agreement with the experiment.

PMID- 24921661
TI  - Inhibitor of differentiation 4 (ID4) inactivation promotes de novo
      steroidogenesis and castration-resistant prostate cancer.
AB  - Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the Western
      world. The transition of androgen-dependent PCa to castration-resistant (CRPC) is
      a major clinical manifestation during disease progression and presents a
      therapeutic challenge. Our studies have shown that genetic ablation of inhibitor
      of differentiation 4 (Id4), a dominant-negative helix loop helix protein, in mice
      results in prostatic intraepithelial neoplasia lesions and decreased Nkx3.1
      expression without the loss of androgen receptor (Ar) expression. ID4 is also
      epigenetically silenced in the majority of PCa. However, the clinical relevance
      and molecular pathways altered by ID4 inactivation in PCa are not known. This
      study investigates the effect of loss of ID4 in PCa cell lines on tumorigenicity
      and addresses the underlying mechanism. Stable silencing of ID4 in LNCaP cells (L
      ID4) resulted in increased proliferation, migration, invasion, and anchorage
      independent growth. An increase in the rate of tumor growth, weight, and volume
      was observed in L-ID4 xenografts compared with that in the LNCaP cells
      transfected with nonspecific short hairpin RNA (L+ns) in noncastrated mice.
      Interestingly, tumors were also observed in castrated mice, suggesting that loss
      of ID4 promotes CRPC. RNA sequence analysis revealed a gene signature mimicking
      that of constitutively active AR in L-ID4, which was consistent with gain of de
      novo steroidogenesis. Prostate-specific antigen expression as a result of
      persistent AR activation was observed in L-ID4 cells but not in L+ns cells. The
      results demonstrate that ID4 acts as a tumor suppressor in PCa, and its loss,
      frequently observed in PCa, promotes CRPC through constitutive AR activation. 

PMID- 24921663
TI  - Anacardic acid enhances the proliferation of human ovarian cancer cells.
AB  - BACKGROUND: Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid
      homologs. Certain antitumor activities of AA have been reported in a variety of
      cancers. However, the function of AA in ovarian cancer, to date, has remained
      unknown. METHODS: Ovarian cancer cell lines were exposed to AA, after which cell
      proliferation, apoptosis, invasion and migration assays were performed.
      Phalloidin staining was used to observe lamellipodia formation. Reverse
      transcription polymerase chain reaction (RT-PCR) and western blotting were used
      to assess the mRNA and protein expression levels of Phosphatidylinositol 3-kinase
      (PI3K), vascular endothelial growth factor (VEGF) and caspase 3. RESULTS: Our
      results showed that AA promotes ovarian cancer cell proliferation, inhibits late
      apoptosis, and induces cell migration and invasion, as well as lamellipodia
      formation. AA exposure significantly up-regulated PI3K and VEGF mRNA and protein
      expression, while, in contrast, it down-regulated caspase 3 mRNA and protein
      expression in comparison to untreated control cells. CONCLUSION: Taken together,
      our results demonstrate for the first time that AA may potentiate the
      proliferation, invasion, metastasis and lamellipodia formation in ovarian cancer
      cell lines via PI3K, VEGF and caspase 3 pathways.

PMID- 24921665
TI  - Transition-metal-assisted radical/radical cross-coupling: a new strategy to the
      oxidative C(sp3)-H/N-H cross-coupling.
AB  - A transition-metal-assisted oxidative C(sp(3))-H/N-H cross-coupling reaction of N
      alkoxyamides with aliphatic hydrocarbons is described. During the reaction,
      nitrogen radicals were generated from the oxidation of N-alkoxyamides.
      Experiments and DFT calculations revealed that transition-metal catalyst could
      lower the reactivity of the generated nitrogen radical by the coordination of the
      transition metal, which allowed the selective radical/radical cross-coupling with
      the transient sp(3) carbon radical to construct C(sp(3))--N bonds. Various
      C(sp(3))-H bonds could be transformed into C(sp(3))-N bonds through this radical
      amidation strategy. 

PMID- 24921664
TI  - Aggregation behavior of chemically synthesized, full-length huntingtin exon1.
AB  - Repeat length disease thresholds vary among the 10 expanded polyglutamine (polyQ)
      repeat diseases, from about 20 to about 50 glutamine residues. The unique amino
      acid sequences flanking the polyQ segment are thought to contribute to these
      repeat length thresholds. The specific portions of the flanking sequences that
      modulate polyQ properties are not always clear, however. This ambiguity may be
      important in Huntington's disease (HD), for example, where in vitro studies of
      aggregation mechanisms have led to distinctly different mechanistic models. Most
      in vitro studies of the aggregation of the huntingtin (HTT) exon1 fragment
      implicated in the HD mechanism have been conducted on inexact molecules that are
      imprecise either on the N-terminus (recombinantly produced peptides) or on the C
      terminus (chemically synthesized peptides). In this paper, we investigate the
      aggregation properties of chemically synthesized HTT exon1 peptides that are full
      length and complete, containing both normal and expanded polyQ repeat lengths,
      and compare the results directly to previously investigated molecules containing
      truncated C-termini. The results on the full-length peptides are consistent with
      a two-step aggregation mechanism originally developed based on studies of the C
      terminally truncated analogues. Thus, we observe relatively rapid formation of
      spherical oligomers containing from 100 to 600 HTT exon1 molecules and
      intermediate formation of short protofibril-like structures containing from 500
      to 2600 molecules. In contrast to this relatively rapid assembly, mature HTT
      exon1 amyloid requires about one month to dissociate in vitro, which is similar
      to the time required for neuronal HTT exon1 aggregates to disappear in vivo after
      HTT production is discontinued. 

PMID- 24921667
TI  - Studies of terbium bridge: saturation phenomenon, significance of sensitizer and
      mechanisms of energy transfer, and luminescence quenching.
AB  - Terbium chain in the form of S -> (Tb(3+))n -> A (S = Ce(3+) or Eu(2+), A =
      Eu(3+)), as a promising energy transfer (ET) approach, has been proposed to
      enhance Eu(3+) emission for solid-state lighting. However, the viewpoint of ET
      from S to A via the terbium chain (Tb(3+)-Tb(3+)-Tb(3+)-...) is very doubtful.
      Here, hosts of Ba3Ln(PO4)3, LnPO4, LnBO3, and Na2Ln2B2O7 doped with Ce(3+) ->
      (Tb(3+))n -> Eu(3+) or (Tb(3+))n -> Eu(3+) are synthesized to prove the
      universality of S -> (Tb(3+))n -> A in inorganic hosts and to study the unsolved
      issues. Saturation distance of Tb(3+)-Eu(3+), estimated with the empirical data
      of different hosts, is proposed to be a criterion for determining whether a
      spectral chromaticity coordinate keeps constant. A branch model is put forward to
      replace the chain model to explain the role of (Tb(3+))n in ET from Ce(3+) to
      Eu(3+) and the necessity of high content of Tb(3+); the term "terbium bridge" is
      used to replace "terbium chain", and the value of n is determined to be two or
      three. The intensity quenching of Eu(3+) emission is attributed to the surface
      defects ascribed to the smaller particles and larger specific surface area rather
      than the concentration quenching of Tb(3+). Based on the saturation distance and
      the mechanism of luminescence quenching, the necessary concentration of Tb(3+)
      for (Tb(3+))n can be estimated as long as the cell parameters are already known
      and the luminescent efficiency of Eu(3+) can be further improved by optimizing
      the synthesis method to decrease the quantity of surface defects. 

PMID- 24921666
TI  - Inferring gene family histories in yeast identifies lineage specific expansions.
AB  - The complement of genes found in the genome is a balance between gene gain and
      gene loss. Knowledge of the specific genes that are gained and lost over
      evolutionary time allows an understanding of the evolution of biological
      functions. Here we use new evolutionary models to infer gene family histories
      across complete yeast genomes; these models allow us to estimate the relative
      genome-wide rates of gene birth, death, innovation and extinction (loss of an
      entire family) for the first time. We show that the rates of gene family
      evolution vary both between gene families and between species. We are also able
      to identify those families that have experienced rapid lineage specific
      expansion/contraction and show that these families are enriched for specific
      functions. Moreover, we find that families with specific functions are repeatedly
      expanded in multiple species, suggesting the presence of common adaptations and
      that these family expansions/contractions are not random. Additionally, we
      identify potential specialisations, unique to specific species, in the functions
      of lineage specific expanded families. These results suggest that an important
      mechanism in the evolution of genome content is the presence of lineage-specific
      gene family changes. 

PMID- 24921668
TI  - Controlling adhesion properties of SWCNT-PET films prepared by wet deposition.
AB  - Due to their unique properties, carbon nanotubes (CNTs) have been used as thin
      electrodes in plastic optoelectronic devices. In many applications, it is
      required that CNT electrodes be transparent, conductive and flexible, and most
      importantly, mechanically stable with good adhesion to the polymeric substrate.
      In this paper, we report on achieving SWCNT transparent and conductive films with
      excellent adhesion to polyethylene terephthalate, without any binder, by a simple
      and rapid post-treatment process. It was found that the best adhesion was
      achieved upon treating the films with acetic acid and formic acid, and with
      solutions containing 1-70% HNO3. Morphological evaluations indicate the unique
      adhesion due to the SWCNT becoming partly embedded within the polymeric substrate
      during the post-treatment process, thus yielding flexible conductive films with
      high transparency. 

PMID- 24921669
TI  - Amplification of hofmeister effect by alcohols.
AB  - We have demonstrated that Hofmeister effect can be amplified by adding alcohols
      to aqueous solutions. The lower critical solution temperature behavior of poly(N
      isopropylacrylamide) has been employed as the model system to study the
      amplification of Hofmeister effect. The alcohols can more effectively amplify the
      Hofmeister effect following the series methanol < ethanol < 1-propanol < 2
      propanol for the monohydric alcohols and following the series d-sorbitol ~
      xylitol ~ meso-erythritol < glycerol < ethylene glycol < methanol for the
      polyhydric alcohols. Our study reveals that the relative extent of amplification
      of Hofmeister effect is determined by the stability of the water/alcohol complex,
      which is strongly dependent on the chemical structure of alcohols. The more
      stable solvent complex formed via stronger hydrogen bonds can more effectively
      differentiate the anions through the anion-solvent complex interactions,
      resulting in a stronger amplification of Hofmeister effect. This study provides
      an alternative method to tune the relative strength of Hofmeister effect besides
      salt concentration. 

PMID- 24921670
TI  - Back to basics: searching for a comprehensive framework for exploring individual
      differences in zebrafish (Danio rerio) behavior.
AB  - Individual differences (IDs) in behavior among nonhuman animals have been
      documented in a wide range of taxa. Although traditionally considered noise
      around an average, other potentially adaptive sources of phenotypic variation
      exist. IDs in behavior that are consistent across time and context are more
      recently recognized as expressions of underlying personality traits, which may
      even be heritable. Unfortunately, despite the rapid advances that have been made
      in animal personality research utilizing fish the last decade, a few have
      detailed the groundwork necessary to document consistency in behavior across time
      and context. This foundation is required, by definition, before one can draw
      conclusions about personality traits. Here, we examine whether IDs in behavior
      are consistent over time and across contexts and explore the construct validity
      of six commonly used behavioral assays for examining four personality traits:
      aggression, boldness, fear, and exploration. Thirty zebrafish (Danio rerio) were
      exposed twice each to a small open field, large open field, mirror, emergence,
      novel object, and predator response test. Results revealed consistency in most
      behavioral measures across both time and context. There was mixed evidence for
      the construct validity of these assays in capturing the targeted personality
      traits.

PMID- 24921671
TI  - A multilocular cystic lesion of the uterine endocervix detected in pregnancy.

PMID- 24921672
TI  - tLyP-1-conjugated Au-nanorod@SiO(2) core-shell nanoparticles for tumor-targeted
      drug delivery and photothermal therapy.
AB  - Mesoporous silica-coated Au nanorod (AuNR@SiO2) is one of the most important
      appealing nanomaterials for cancer therapy. The multifunctions of chemotherapy,
      photothermal therapy, and imaging of AuNR@SiO2 make it very useful for cancer
      therapy. In this study, AuNR@SiO2 was functionalized to deliver hydrophobic
      antitumor drug and to heat the targeted tumor with the energy of near-infrared
      (NIR). To carry out the function of targeting the tumor, tLyP-1, a kind of tumor
      homing and penetrating peptide, was engrafted to AuNR@SiO2. The fabricated
      AuNR@SiO2-tLyP-1 which was loaded with camptothecin (CPT) showed a robust,
      selective targeting and penetrating efficiency to Hela and MCF-7 cells and
      induced the death of these cells. When the micromasses of these AuNR@SiO2-tLyP-1
      internalized cells were irradiated by NIR illumination, all the cells were killed
      instantaneously owing to the increased temperature caused by the surface plasma
      resonance (SPR) of the internalized AuNR@SiO2-tLyP-1. Moreover, the systematic
      toxicity of CPT-loaded AuNR@SiO2-tLyP-1 on human mesenchymal stem cells (hMSCs)
      was minimized, because the AuNR@SiO2-tLyP-1 selectively targeted and penetrated
      into the tumor cells, and little hydrophobic CPT was released into the culture
      medium or blood. This study indicates that the AuNR@SiO2-tLyP-1 drug delivery
      system (DDS) has great potential application for the chemo-photothermal cancer
      therapy. 

PMID- 24921673
TI  - Spermidine cross-linked hydrogels as a controlled release biomimetic approach for
      cloxacillin.
AB  - The intrinsic ability of albumin to bind active substances in the physiological
      fluids has been explored to endow hydrogels with improved capability to regulate
      drug release. To develop such biomimetic-functional hydrogels, it is critical
      that albumin conformation is not altered and that the protein remains retained
      inside the hydrogel keeping its conformational freedom, i.e., it should be not
      chemically cross-linked. Thus, the hydrogels were prepared with various
      proportions of albumin by physical cross-linking of anionic polysaccharides
      (gellan gum and chondroitin sulfate) with the cationic endogen polyamine
      spermidine under mild conditions in order to prevent albumin denaturation.
      Texture and swelling properties of hydrogels with various compositions were
      recorded, and the effect of the preparation variables was evaluated applying
      neurofuzzy logic tools for hydrogels prepared with and without albumin and
      associating the antibiotic cloxacillin. Developed hydrogel systems were
      extensively analyzed by means of nuclear magnetic resonance (NMR) to determine
      weak-to-medium and strong binding modes and the equilibrium constants of the
      albumin-cloxacillin association. NMR techniques were also employed to demonstrate
      the successful modulation of the cloxacillin release from the albumin-containing
      hydrogels. In vitro microbiological tests carried out with Staphylococcus aureus
      and Staphylococcus epidermidis confirmed the interest of the albumin-containing
      hydrogels as efficient platforms for cloxacillin release in its bioactive form. 

PMID- 24921674
TI  - Dexmedetomidine as adjuvant therapy for acute postoperative neuropathic pain
      crisis.
AB  - BACKGROUND: Dexmedetomidine is a potent alpha2-adrenergic agonist U.S. Food and
      Drug Administration (FDA) approved for sedation. While its use as an analgesic
      has been described in the palliative medicine literature, its use for managing an
      acute neuropathic pain episode is less well known. METHODS: Here we describe the
      use of adjuvant dexmedetomidine in a patient with metastatic sarcoma suffering
      from an acute postoperative neuropathic pain crisis. CONCLUSION: Among patients
      with acute neuropathic pain for whom additional opioids raises respiratory
      related concerns, the use of dexmedetomidine should be considered as a viable
      treatment alternative.

PMID- 24921675
TI  - SNRIs-All for one and one for all?

PMID- 24921676
TI  - Serotonin noradrenaline reuptake inhibitors: Logical evolution of antidepressant
      development.
AB  - Although considerable progress has been made in improving the tolerability of
      antidepressant drugs, the classical tricyclic antidepressants (TCA) are still a
      standard for efficacy. The selective serotonin reuptake inhibitors (SSRI) are
      much better tolerated than the TCAs, but their antidepressant efficacy is, at
      best, equivalent and probably inferior to the TCA, clomipramine, in many
      situations. The introduction of the SSRIs naturally focussed both fundamental and
      clinical research effort on the role of serotonin (5-HT) in the pharmacogenesis
      and pharmacotherapy of depression. More recently the probable role of
      noradrenaline (NA) has been "rediscovered" and increasingly both 5-HT and NA
      dysfunctions are seen as fundamental to depressive illness. The therapeutic
      importance of this has been underlined by studies showing the increased
      antidepressant efficacy obtained when selective serotonergic drugs have been used
      in conjunction with selective noradrenergic drugs. The development of the new
      class of serotonin and noradrenaline reuptake inhibitors (SNRI) was a logical
      extension of these ideas. Compounds of this class, which currently comprises
      venlafaxine, milnacipran and duloxetine, act to inhibit the reuptake of both
      monoamines with no direct actions at postsynaptic receptors. Although, by
      definition all three SNRIs have actions on both 5-HT and NA neurotransmission,
      they do not all have equal potency for both transmitters. Venlafaxine has a 30
      fold higher affinity for 5-HT than NA while duloxetine has a 10-fold selectivity
      for 5-HT. Only milnacipran is balanced between the two neurotransmitters with an
      approximately equal potency for the inhibition of reuptake of 5-HT and NA both in
      vitro and in vivo. At high doses venlafaxine and duloxetine appear to be superior
      to SSRIs but not at lower doses. Duloxetine is, however, not licensed in the EU
      at these higher doses. Milnacipran at usual doses appears more effective than
      SSRIs with efficacy which is similar to TCAs but with a lower side effect burden.

PMID- 24921677
TI  - Serotonin noradrenaline reuptake inhibitors: A new generation of treatment for
      anxiety disorders.
AB  - A variety of agents are currently used to treat the different anxiety disorders.
      Benzodiazepines, such as diazepam, are still preferred by some for the treatment
      of acute anxiety, with the advantage of a rapid onset of action, but they are
      less suitable for long-term treatment due to their potential for memory
      disturbances, sleepiness, lethargy, physical dependence and withdrawal. Compounds
      acting on monoamine neurotransmission are more suitable in the treatment of long
      term or chronic anxiety disorders. Tricyclic antidepressants, such as imipramine,
      and monoamine oxidase inhibitors have been shown to be effective anxiolytics, but
      their side effects and safety concerns have limited their use. The probable role
      of disturbed serotonergic neurotransmission in anxiety is widely accepted and is
      the theoretical basis for the use of serotonergic agents such as the 5-HT1A
      receptor partial agonist, buspirone, and the selective serotonin reuptake
      inhibitors (SSRI), such as sertraline and paroxetine, which have largely replaced
      the earlier antidepressants. There is clear evidence for decreased serotonergic
      function in anxiety as well as in depression. Studies of patients with anxiety
      disorders show reduced levels of serotonin in cerebrospinal fluid (CSF) as well
      as reduced serotonin transporter binding. The role of noradrenaline in the
      control of anxiety is less well understood, although there is considerable
      evidence to suggest that a disturbance of noradrenergic neurotransmission may
      also contribute to the symptoms of anxiety. Noradrenaline modulates the activity
      of brain regions such as the amygdala which are associated with anxiety. In
      addition, anxiety states are associated with increases in the metabolite of
      noradrenaline, 3-methoxy-4-hydrophenylglycol (MHPG), and hypersecretion of
      noradrenaline in plasma and CSF. It appears likely that modulation of both
      serotonin and noradrenaline systems by dual-reuptake inhibitors may prove to be
      an advantage in the treatment of anxiety disorders. The serotonin-noradrenaline
      reuptake inhibitors (SNRI), venlafaxine, milnacipran and duloxetine are
      efficacious in relieving anxiety symptoms within depression, and some have proven
      efficacy in certain anxiety disorders. Initial studies suggest that dual acting
      agents may have an advantage over selective reuptake inhibitors in certain
      anxiety disorders, such as post-traumatic stress disorder (PTSD), and in patients
      with comorbid anxiety and depression. 

PMID- 24921678
TI  - Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of
      chronic pain.
AB  - Depression and painful symptoms occur frequently together. Over 75% of depressed
      patients report painful symptoms such as headache, stomach pain, neck and back
      pain as well as non-specific generalized pain. In addition, World Health
      Organization data have shown that primary care patients with chronic pain have a
      four fold greater risk of becoming depressed than pain-free patients.
      Increasingly, pain is considered as an integral symptom of depression and there
      evidence to suggest that pain and depression may arise from a common
      neurobiological dysfunction. Serotonergic cell bodies, in the raphe nucleus, and
      noradrenergic cell bodies in the locus coeruleus send projections to various
      parts of the brain, where they are involved in the control of mood, movement,
      cognitive functioning and emotions. In addition both serotonergic and
      noradrenergic neurons project to the spinal cord. These descending pathways serve
      to inhibit input from the intestines, skeletal muscles and other sensory inputs.
      Usually, these inhibitory effects are modest, but in times of stress, in the
      interest of the survival of the individual, they can completely inhibit the input
      from painful stimuli. A dysfunction of the serotonergic and noradrenergic neurons
      can thus affect both the ascending and descending pathways resulting in the
      psychological symptoms of depression and somatic pain symptoms such as chronic
      pain, fibromyalgia, non-cardiac chest pain, or irritable bowel syndrome. In view
      of this, it is not surprising that tricyclic antidepressants have been a standard
      treatment of chronic pain for many years. In contrast and in spite of their
      improved tolerance, selective serotonin reuptake inhibitors do not appear to be
      particularly effective in the treatment of pain. Recently, a number of open and
      controlled trials with selective serotonin and noradrenaline reuptake inhibitors
      such as venlafaxine, milnacipran and duloxetine, suggest that these compounds may
      be more effective in relieving pain than selective inhibitors of serotonin
      reuptake. Wherever valid comparisons have been made the newer dual action drugs
      appear to be as effective as the tricyclic and considerably better tolerated.
      Dual action antidepressants may thus soon become the new standard treatment of
      chronic pain whether it is associated with depression or not. In addition, these
      agents may also have a role in modulating neurogenesis and other neuroplastic
      changes in the central nervous system, thereby leading to more complete recovery
      in patients suffering from the symptoms of depression or chronic pain. 

PMID- 24921679
TI  - Dual serotonin and noradrenaline reuptake inhibitors: Focus on their differences.
AB  - There are three non-tricyclic dual serotonin (5-HT) and noradrenaline (NA)
      reuptake inhibitors (SNRIs) currently used in human therapeutics for psychiatric
      disorders. These medications differ in their in vitro potency to inhibit 5-HT and
      NA reuptake with differential ratios of activity. Using in vivo studies carried
      out in laboratory animals, which better reflect human physiology than experiments
      using lysed tissue in a test tube, venlafaxine is about three times more potent
      on 5-HT than NA reuptake, duloxetine five times, and milnacipran is about twice
      more potent on NA than 5-HT reuptake. Sustained administration of SNRIs induces
      different adaptive effects on presynaptic 5-HT and NA receptors controlling the
      function of 5-HT and NA neurons, suggesting that they may differentially affect
      transmission of these two neuronal systems. In the treatment of depression, SNRIs
      appear to have similar effectiveness and when compared to selective 5-HT reuptake
      inhibitors, they generally exert a superior antidepressant effect. Taken
      together, these observations suggest that individual patients not responding to a
      SNRI may present a favourable response to another agent within that family. SNRIs
      have different pharmacokinetic properties and exert distinct effects on the
      activity of liver metabolic enzymes. These features of SNRIs can help clinicians
      tailor treatment to individual patients. 

PMID- 24921680
TI  - A 5-(difluorenyl)-1,10-phenanthroline-based Ru(II) complex as a coating agent for
      potential multifunctional gold nanoparticles.
AB  - The synthesis and photophysical properties of small gold nanoparticles (NPs, AuNP
      [Ru-PFF]) surface functionalized by 5-substituted-1,10-phenanthroline-ligand
      based Ru(II) complexes are described. Luminescence of the grafted and confined
      Ru(II) complexes is totally quenched on the gold surface. Nonlinear optical
      properties were determined via Z-scan measurements in the range 600-1300 nm for
      both the free Ru(II) complex and the related NPs. In the short wavelength range
      (around 600 nm) the behaviour switches from that of two-photon absorption (2PA)
      for the complex to saturable absorption for the NPs. 2PA applications such as
      optical power limiting or two-photon dioxygen sensitization can be anticipated
      for these nanoplatforms.

PMID- 24921681
TI  - An ESIPT fluorescent probe sensitive to protein alpha-helix structures.
AB  - A large majority of membrane proteins have one or more transmembrane regions
      consisting of alpha-helices. Membrane protein levels differ from one type of cell
      to another, and the expression of membrane proteins also changes from normal to
      diseased cells. For example, prostate cancer cells have been reported to have
      downregulated expression of membrane proteins, including zinc transporters,
      compared with normal prostate cells. These reports inspired us to design a
      fluorescence probe sensitive to protein alpha-helical structures to discriminate
      individual prostate cancer cells from normal ones. A benzazole derivative ( in
      this study) was observed to emit strong fluorescence resulting from an excited
      state intramolecular proton transfer (ESIPT) in protein alpha-helical
      environments. The intensity of ESIPT fluorescence of was observed to be
      positively correlated with the alpha-helix content of proteins. The molecular
      docking simulation suggested that it had low energy for the binding of to
      proteins when the binding sites were localized within the alpha-helical regions
      of protein via H-bonds. Furthermore, was found to be localized in cell membranes
      through binding to transmembrane alpha-helical regions of membrane proteins, and
      was capable of probing differences in the alpha-helix contents of membrane
      proteins between normal and cancerous prostate cells through changes in the ESIPT
      emission intensity. These results indicated that could distinguish individual
      prostate cancer cells from normal ones, as the changes in the ESIPT fluorescence
      intensity of could reflect the regulation in expression of the membrane proteins
      including zinc transporters. This recognition strategy of individual prostate
      cancer cells might contribute to early diagnosis techniques for prostate cancer. 

PMID- 24921682
TI  - A systematic review of medication administration errors with transdermal patches.
AB  - INTRODUCTION: Transdermal patches provide an attractive route of drug delivery
      with considerable advantages over other routes of administration, for example
      maintenance of constant plasma drug levels and convenient usage. However,
      medication administration errors abound with this dosage form and frequently
      result in harm or treatment failure. AREAS COVERED: A systematic literature
      search was conducted according to the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines using appropriate keywords to identify
      articles reporting faulty transdermal patch administration. Common pitfalls and
      errors that were identified through the systematic literature search were
      discussed alongside individual steps of the transdermal patch administration
      process. EXPERT OPINION: The systematic investigation of published errors
      illustrated that every step in the transdermal patch administration process is
      prone to errors. Thereby, the lack of knowledge and awareness of the importance
      of a correct administration practice were a major source of risk. Based on the
      identified errors and causes of errors prevention strategies were developed as a
      first step in avoiding transdermal patch administration errors.

PMID- 24921683
TI  - Sex education in the 21st century.

PMID- 24921684
TI  - ICPD beyond 2014: moving beyond missed opportunities and compromises in the
      fulfilment of sexual and reproductive health and rights.
AB  - The 1994 International Conference on Population and Development (ICPD) in Cairo
      marked a paradigm shift that took family planning out of a population control
      context and into the broader context of sexual and reproductive health and rights
      (SRHR). While progress has been made with increased access to family planning and
      a decrease in maternal deaths, we have not seen practical results for the
      majority of women and girls worldwide, who still experience unacceptably high
      rates of maternal deaths, unmet contraceptive needs and HIV infections. Three of
      the compromises made by governments at Cairo - integration, reproductive rights
      and resource allocation - hindered the fulfilment of women's and girls' SRHR. The
      post-2015 agenda must ensure that economic development and global health
      interventions are linked at the national and global levels; family planning, HIV,
      maternal health and other reproductive health services are integrated and
      delivered through primary health settings; and access to safe and voluntary
      abortion services is recognised as a human right. Non-governmental organisations
      and donors must move beyond siloed issue areas to challenge governments,
      multilateral agencies, the financial sector and each other to ensure that the
      promise of SRHR is realised. 

PMID- 24921685
TI  - Estimation of the intramolecular O-H...O?C hydrogen bond energy via the molecular
      tailoring approach. Part I: aliphatic structures.
AB  - A simple and universal method for the estimation of the intramolecular hydrogen
      bond (HB) energy (E(HB)) in hydroxycarbonyl aliphatic compounds is proposed by
      the application of the molecular tailoring approach (MTA) based on calculations
      at the second-order Moller-Plesset MP2 level. The calculation of EHB can be
      realized by the one optimization and three single point calculations of the
      energy for each compound with carbonyl and hydroxyl groups involved in HB. The
      intramolecular hydrogen bond energies estimated for 153 structures (of 102
      compounds) ranged from 1.4 to 13.7 kcal/mol for systems without resonance
      assisted hydrogen bonding (RAHB). To verify the method, we show the correlations
      of the energy (E(HB)) in six-, seven-, and eight-membered HB rings in the
      optimized multifunctional molecules with the usual geometry descriptors of
      hydrogen bonds. Moreover, topological parameters from the atoms in molecules
      (AIM) theory and the calculated infrared and proton NMR spectra are correlated.
      The effects of conjugation and pi-electron delocalization, bifurcation, and
      cooperativity are discussed, along with the correlation between the strength and
      geometrical parameters of H bonding.

PMID- 24921686
TI  - A light-gated molecular brake with antilock and fluorescence turn-on alarm
      functions: application of singlet-state adiabatic cis -> trans
      photoisomerization.
AB  - A light-gated molecular brake that displays both high braking power (~10(7)) and
      high switching power (~74%) is reported. The lower rate for brake-on than for
      brake-off switching of the pentiptycene rotor mimics the function of an antilock
      braking system (ABS) for vehicles on a loose surface. The brake is also armed
      with a fluorescence turn-on alarm for accidental deactivation of the ABS function
      by acids. All of these features are associated with the highly efficient singlet
      state adiabatic cis -> trans photoisomerization of the phenylstilbene
      chromophore. 

PMID- 24921689
TI  - Editorial.

PMID- 24921687
TI  - Synthesis of luminescent nanoporous silica spheres functionalized with folic acid
      for targeting to cancer cells.
AB  - Luminescent europium(III)-doped nanoporous silica nanospheres (Eu:NPS) were
      successfully synthesized, and a folate N-hydroxysuccinimidyl ester (FA-NHS)
      molecule as a targeting ligand for cancer cells was immobilized on the nanosphere
      surfaces through mediation of the 3-aminopropyltriethoxysilane (APTES) adlayer.
      The ordered nanopores were preserved by the immobilization, and the specific
      surface area decreased only with the APTES immobilization, suggesting that the FA
      NHS was predominantly immobilized on the outer surface of the nanopores. The
      photoluminescence of the nanospheres functionalized with folic acid (FA)
      exhibited a characteristic peak due to the interactions (e.g., energy transfer)
      between FA and Eu(3+), and further the orange luminescence could be clearly
      detected by fluorescence microscopy in air and water. Furthermore, the
      nanospheres highly dispersed in cell culture medium exhibited nontoxicity in the
      cellular proliferation stages of the Hela cancer cells and NIH3T3 fibroblasts and
      specifically bind to the Hela cells. The nanospheres after the binding and uptake
      also showed intense luminescence from the outer/inner cell surfaces for the
      culture time of 4 days. Therefore, the luminescent FA-functionalized Eu:NPS
      nanospheres could be used for specific targeting and imaging abilities for cancer
      cells. 

PMID- 24921688
TI  - The impact of breastfeeding on nasopharyngeal microbial communities in infants.
AB  - RATIONALE: Breastfeeding elicits significant protection against respiratory tract
      infections in infancy. Modulation of respiratory microbiota might be part of the
      natural mechanisms of protection against respiratory diseases induced by
      breastfeeding. OBJECTIVES: To study the association between breastfeeding and
      nasopharyngeal microbial communities, including all cultivable and noncultivable
      bacteria. METHODS: In this observational study, we analyzed the microbiota of
      infants that had received exclusive breastfeeding (n = 101) and exclusive formula
      feeding (n = 101) at age 6 weeks and 6 months by 16S-based GS-FLX-titanium
      pyrosequencing. MEASUREMENTS AND MAIN RESULTS: At 6 weeks of age the overall
      bacterial community composition was significantly different between breastfed and
      formula-fed children (nonmetric multidimensional scaling, P = 0.001). Breastfed
      children showed increased presence and abundance of the lactic acid bacterium
      Dolosigranulum (relative effect size [RES], 2.61; P = 0.005) and Corynebacterium
      (RES, 1.98; P = 0.039) and decreased abundance of Staphylococcus (RES, 0.48; P
      0.03) and anaerobic bacteria, such as Prevotella (RES, 0.25; P < 0.001) and
      Veillonella (RES, 0.33; P < 0.001). Predominance (>50% of the microbial profile)
      of Corynebacterium and Dolosigranulum was observed in 45 (44.6%) breastfed
      infants compared with 19 (18.8%) formula-fed infants (relative risk, 2.37; P =
      0.006). Dolosigranulum abundance was inversely associated with consecutive
      symptoms of wheezing and number of mild respiratory tract infections experienced.
      At 6 months of age associations between breastfeeding and nasopharyngeal
      microbiota composition had disappeared. CONCLUSIONS: Our data suggest a strong
      association between breastfeeding and microbial community composition in the
      upper respiratory tract of 6-week-old infants. Observed differences in microbial
      community profile may contribute to the protective effect of breastfeeding on
      respiratory infections and wheezing in early infancy. Clinical trial registered
      with www.clinicaltrials.gov (NCT 00189020).

PMID- 24921690
TI  - Caffeine: The forgotten variable.
AB  - Although the majority of the population regularly consume caffeine, there are
      wide variations between individuals in both daily intake and susceptibility to
      caffeine's effects. These differences are at least partially genetically
      determined, possibly via variations in adenosine receptors or caffeine
      metabolism. Caffeine toxicity is well recognized. Tolerance of its effects and
      withdrawal symptoms have also been described. Both DSM and ICD-10 recognize
      caffeine as a potential drug of abuse. Caffeine can induce anxiety, exacerbate
      psychotic symptoms in some patients with schizophrenia and cause insomnia. It can
      complicate the management of depression by increasing lithium clearance and can
      also increase seizure length during ECT. Caffeine can inhibit the metabolism of
      some psychotropic drugs such as clozapine through the competitive inhibition of
      CYP 1A2 . Potent inhibitors of CYP 1A2 such as fluvoxamine can precipitate
      caffeine toxicity. Enquiries about caffeine consumption should be made in all
      patients who have apparently treatment-refractory illness, or seem unusually
      sensitive to, or tolerant of, psychotropic drugs. 

PMID- 24921691
TI  - Tryptophan depletion as a clinical tool: Current status and future directions.
AB  - The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays important roles
      in many basic functions: mood, feeding, anxiety, sleep, emesis, sexual function,
      thermoregulation, and cardiovascular tone. Over the past 10 years, tryptophan
      depletion (TD) studies of 5-HT function have emerged as an important clinical
      tool for studying brain serotonergic systems, and their relevance to practising
      psychiatrists has grown steadily. In this review, we discuss the evolution of TD
      studies and their continuing utility in understanding the role of 5-HT in
      psychiatric disorders and the development of more effective treatments. 

PMID- 24921692
TI  - The effect of treatment with risperidone, olanzapine or phenothiazines on
      cognitive functions in patients with schizophrenia.
AB  - INTRODUCTION: Theaimofthestudywastocomparetheeffectsofrisperidone, olanzapine and
      phenothiazines on cognitive functions in schizophrenia during short-term (4 &#45
      6 weeks) and long-term (3 &#45 4 months) treatment. METHOD: Seventy patients with
      schizophrenia were investigated: 30 treated with risperidone, 20 with olanzapine
      and 20 with phenothiazines, in standard doses. Psychometric measurements were
      made with the Positive and Negative Syndrome Scale (PANSS), and
      neuropsychological tests included the Trail Making Test (TMT), the Stroop Test
      and the Wisconsin Card Sorting Test (WCST). RESULTS: PANSS negative symptoms
      decreased significantly after risperidone and olanzapine, did not change after
      short-term, and improved marginally after long-term, phenothiazine treatment.
      Risperidone treatment resulted in significant amelioration of performance on all
      neuropsychological tests after both short- and long-term treatment. Olanzapine
      gave benefit on five out of seven subtests, although in most instances this
      effect was noted only after long-term treatment. Olanzapine was inferior to
      risperidone in improving WCST performance. Treatment with phenothiazines brought
      about improvement on two subtests while the results on three showed significant
      deterioration. CONCLUSION: The results obtained suggest that novel antipsychotics
      show differential effect on cognition, with risperidone especially improving
      working memory; however, their effect on negative symptoms and cognitive
      functions is better than that of typical neuroleptics.

PMID- 24921693
TI  - Atypical antipsychotics in the elderly.
AB  - INTRODUCTION: Although their primary purpose is to treat psychosis,
      antipsychotics are commonly prescribed for the elderly to treat the behavioural
      disturbances and agitation associated with dementia. Such use is controversial.
      Atypical antipsychotics cause fewer extrapyramidal sideeffects than the older
      drugs in younger adults, but the evidence base for their efficacy and
      tolerability in the elderly is poor. The aims of this study were to determine the
      prevalence of atypical antipsychotic prescribing for the elderly, the indications
      for use and documented side-effects. METHOD: The medication cards of all patients
      from 19 Trusts, occupying a psychiatric bed for the over 65s, were screened
      during one week in March 2000. Data were collected by pharmacists from the
      clinical notes. RESULTS: Half of those prescribed an antipsychotic received an
      atypical, and risperidone was the one most commonly prescribed. Half the sample
      had a diagnosis of dementia. Documented side-effects from the atypical were
      uncommon. CONCLUSION: Atypicals are frequently prescribed as first-line
      antipsychotics for behavioural problems associated with dementia, despite the
      poor evidence base for their efficacy and safety in this population.
      Undermonitoring of side-effects may remain a problem.

PMID- 24921694
TI  - A comparison of the service satisfaction and intervention needs of patients with
      schizophrenia and their relatives.
AB  - INTRODUCTION: Patients with psychotic illness are frequently dissatisfied with
      psychiatric services although it is unclear whether this can be explained as
      being due to the mental disorder itself, or to the lower quality of care received
      by this group of patients. We explored this issue by comparing service
      satisfaction from different user perspectives: patients and key relatives.
      METHOD: The satisfaction and needs of 52 patients with schizophrenia and 66 of
      their relatives were assessed using the Verona Service Satisfaction Scale (VSSS).
      RESULTS: Patients were generally more satisfied with services than relatives, but
      there was a high degree of consistency between the groups regarding the aspects
      of the service which they were most, and least, satisfied with. CONCLUSION:
      Patient satisfaction surveys can be used as reliable indicators of service
      quality and can highlight specific strengths and shortcomings in mental health
      service provision. Such surveys can be very useful to help improve the quality of
      care for patients and their relatives.

PMID- 24921695
TI  - Diagnostic approaches to borderline personality and their relationship to self
      harm behavior.
AB  - OBJECT: This study was designed to explore the relationship, if any, between
      diagnostic approach to borderline personality disorder (BPD) and the extent of
      self-harm behavior among psychiatric inpatients. METHOD: Newly admitted
      psychiatric inpatients (N =77) were evaluated for BPD using a self-report
      measure, clinical diagnosis, and a DSM-IV checklist. All participants were
      assessed for self-harm behavior using the 22-item Self-Harm Inventory (SHI).
      RESULTS: Participants with a clinical diagnosis of BPD showed the highest
      prevalence of, and most potentially lethal, types of self-harm behavior, followed
      by those diagnosed as BPD by the DSM-IV checklist, and then by self-report
      measure. Participants diagnosed as BPD on all three measures showed the highest
      mean number of self-harm and potentially lethal behavior types. Prevalence and
      potential lethality decreased successively among those who were diagnosed as BPD
      on two measures versus one measure versus no diagnosis of BPD. CONCLUSION: Self
      harm behavior appears to be a clinically concordant behavior type among the
      diagnostic approaches to BPD used in this study. Clinical diagnosis appears most
      sensitive to self-harm behavior, compared with self-report and DSM-IV checklist.

PMID- 24921696
TI  - Paroxetine in panic disorder with agoraphobia.
AB  - A case of a panic disorder patient treated successfully in the long term with a
      selective serotonin re-uptake inhibitor, paroxetine, is reported. Based on this
      case, the relationship between pharmacotherapy and psychotherapy is discussed. 

PMID- 24921697
TI  - Quetiapine in acute mania: a case report (with a six-month follow-up).
AB  - Quetiapine is an effective and well-tolerated antipsychotic. To date, experience
      with quetiapine in bipolar disorders is very limited and information on the use
      in acute patients is lacking. A patient with a DSMIV diagnosis of acute mania
      intolerant to lithium and to neuroleptics was treated with quetiapine. The daily
      dosage of quetiapine was gradually titrated up to 600 mg t.i.d. Quetiapine was
      effective, as evidenced by rating scale scores of the BPRS, YMRS and CGI, which
      dropped by 91% and 94% respectively from baseline (devoid of relevant side
      effects). Quetiapine seems to be a promising agent for the treatment of manic
      episodes in bipolar disorders, although controlled trials are needed. 

PMID- 24921698
TI  - Successful treatment of rhabdomyolysis and acute renal failure following
      amoxapine overdose.
AB  - Amoxapine, a tricyclic antidepressant, is widely used by psychiatrists. While
      overdose of tricyclic antidepressants is known to be dangerous and potentially
      fatal (causing hypotension, arrhythmia, convulsions, respiratory failure, and
      other serious complications), overdose of amoxapine can cause other problems, and
      metabolic acidosis, seizures, neuroleptic malignant syndrome, and arrhythmia have
      been reported. This report describes the case of a patient who developed
      rhabdomyolysis and acute renal failure following amoxapine overdose. Continuous
      hemofiltration was instituted twice, and he recovered without sequelae; this
      suggests the effectiveness of continuous hemofiltration and its possibilities in
      the treatment of amoxapine overdose and acute renal failure due to
      rhabdomyolysis. 

PMID- 24921699
TI  - Post-traumatic stress disorder in a patient with an implant cardioverter
      defibrillator.
AB  - The authors describe a patient using cardioverter-defibrillator implant therapy
      (CDIT) after a blood pressure elevation and arrhythmia episode. The CDIT
      delivered 9 defibrillating discharges in a 24 hour period until a new
      stabilization was achieved. The patient developed a post-traumatic stress
      disorder with no improvement with the use of 15 mg of diazepam b.i.d. He was
      referred to a psychiatrist 4 months later, received Sertraline 100 mg b.i.d., and
      supportive therapy and achieved a total remission in 6 weeks. This case report
      illustrates the psychiatric comorbidity in the &#164 survivor' population, a
      group of patients who survive due to advances in medical technology. The
      psychiatric study of them is a challenge to the improvement of their quality of
      life. Assessment and treatment of mental disorder may improve the quality of life
      for this patient group. 

PMID- 24921700
TI  - A common dementia in a rare disease.
AB  - The patient described was a 68-year-old man presenting with a severe, subacute
      depressive state with rapid decline in memory, psychomotor retardation and
      refusal to eat, who was referred by the medical team for ECT. His memory
      impairment could not be explained within the context of his depressed mood and he
      was eventually found to have a primary cerebral lymphoma of the non-Hodgkin's
      type. He died 10 weeks after initial psychiatric assessment. 

PMID- 24921701
TI  - Topics in contemporary psychiatric practice: Weight Gain.

PMID- 24921703
TI  - Heterodinuclear M(II)-Ln(III) single molecule magnets constructed from exchange
      coupled single ion magnets.
AB  - The synthesis and characterization of four dinuclear 3d-4f complexes
      [M(II)Ln(III)(L)(DBM)3] (ZnDy = 1, CoY = 2, CoDy = 3.3.5CH3CN, CoGd = 4.3.5CH3CN)
      are reported (H2L = N,N'-dimethyl-N,N'-(2-hydroxy-3-methoxy-5-methyl
      benzyl)ethylenediamine, DBM(-) = anion of 1,3-diphenyl-propane-1,3-dione). In
      each of the four complexes, the M(II) ion occupies the internal N2O2 site whereas
      the Ln(III) ion occupies the external O4 site. There are diphenoxo bridges
      between the M(II) and Ln(III) ions in these complexes. The remaining coordination
      sites are occupied by three DBM(-) anions. Direct current (dc) magnetic
      susceptibility measurements indicate the presence of intramolecular ferromagnetic
      interactions in complexes 3 and 4. The magnetic coupling constant, JCoGd, of
      complex 4 is estimated to be 0.26 cm(-1) (H = -2JCoGdSCoSGd). Alternating current
      (ac) magnetic susceptibility studies reveal that complexes 1 and 2 show field
      induced single molecule magnet behavior, with DeltaE values of 36.5 K and 8.56 K,
      respectively. Complex 3 shows frequency dependent out-of-phase signals,
      indicating the presence of a slow relaxation of the magnetization, whereas
      complex 4 does not display slow magnetization relaxation. 

PMID- 24921704
TI  - Pertuzumab for the treatment of breast cancer.
AB  - HER2-targeted therapies have revolutionized the outcome of patients with HER2
      positive breast cancer. Pertuzumab is the first in a new class of monoclonal
      antibodies that target the extracellular dimerization domain of HER2 receptors,
      also known as HER dimerization inhibitors. The development of pertuzumab and
      preclinical and clinical data in breast cancer are reviewed. Regulatory affairs
      related to pertuzumab and the recent accelerated approval granted by the FDA for
      the treatment of breast cancer in the neoadjuvant setting are also covered. This
      process opens doors for further approvals which could considerably shorten the
      time between initial drug development and availability. 

PMID- 24921705
TI  - Computational study on substrate specificity of a novel cysteine protease 1
      precursor from Zea mays.
AB  - Cysteine protease 1 precursor from Zea mays (zmCP1) is classified as a member of
      the C1A family of peptidases (papain-like cysteine protease) in MEROPS (the
      Peptidase Database). The 3D structure and substrate specificity of the zmCP1 is
      still unknown. This study is the first one to build the 3D structure of zmCP1 by
      computer-assisted homology modeling. In order to determine the substrate
      specificity of zmCP1, docking study is used for rapid and convenient analysis of
      large populations of ligand-enzyme complexes. Docking results show that zmCP1 has
      preference for P1 position and P2 position for Arg and a large hydrophobic
      residue (such as Phe). Gly147, Gly191, Cys189, and Asp190 are predicted to
      function as active residues at the S1 subsite, and the S2 subsite contains
      Leu283, Leu193, Ala259, Met194, and Ala286. SIFt results indicate that Gly144,
      Arg268, Trp308, and Ser311 play important roles in substrate binding. Then
      Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) method was used to
      explain the substrate specificity for P1 position of zmCp1. This study provides
      insights into the molecular basis of zmCP1 activity and substrate specificity. 

PMID- 24921706
TI  - Estrogen rapidly enhances incisional pain of ovariectomized rats primarily
      through the G protein-coupled estrogen receptor.
AB  - It has become increasingly apparent that the pain threshold of females and males
      varies in an estrogen dependent manner. To investigate the modulation of pain by
      estrogen and the molecular mechanisms involved in this process. A total of 48
      rats were ovariectomized (OVX). At 14 and 20 days after OVX, rats were divided
      into eight groups: groups 1-4 were administered drugs intravenously (IV); groups
      5-8 were administered through intrathecal (IT) catheter. Hind paw incision was
      made in all animals to determine incisional pain. Paw withdraw threshold (PWT)
      was tested prior to and 24 h after incision. The test drugs were applied 24 h
      after the incision. Rats were either IV or IT administered with: 17-beta
      estradiol (E2), G protein-coupled estrogen receptor (GPER)-selective agonist
      (G1), GPER-selective antagonist (G15) and E2 (G15+E2), or solvent. Before and 30
      min after IV drug administration and 20 min during the IT catheter
      administration, PWT was tested and recorded. 24 h after incisional surgery, the
      PWT of all rats significantly decreased. Both in the IV group and IT group:
      administration of E2 and G1 significantly decreased PWT. Neither administration
      of G15+E2 nor solvent significantly changed PWT. Estrogen causes rapid reduction
      in the mechanical pain threshold of OVX rats via GPER.

PMID- 24921707
TI  - Mass spectrometry methodology in lipid analysis.
AB  - Lipidomics is an emerging field, where the structures, functions and dynamic
      changes of lipids in cells, tissues or body fluids are investigated. Due to the
      vital roles of lipids in human physiological and pathological processes,
      lipidomics is attracting more and more attentions. However, because of the
      diversity and complexity of lipids, lipid analysis is still full of challenges.
      The recent development of methods for lipid extraction and analysis and the
      combination with bioinformatics technology greatly push forward the study of
      lipidomics. Among them, mass spectrometry (MS) is the most important technology
      for lipid analysis. In this review, the methodology based on MS for lipid
      analysis was introduced. It is believed that along with the rapid development of
      MS and its further applications to lipid analysis, more functional lipids will be
      identified as biomarkers and therapeutic targets and for the study of the
      mechanisms of disease. 

PMID- 24921709
TI  - On interlayer stability and high-cycle simulator performance of diamond-like
      carbon layers for articulating joint replacements.
AB  - Diamond like carbon (DLC) coatings have been proven to be an excellent choice for
      wear reduction in many technical applications. However, for successful adaption
      to the orthopaedic field, layer performance, stability and adhesion in
      physiologically relevant setups are crucial and not consistently investigated. In
      vitro wear testing as well as adequate corrosion tests of interfaces and
      interlayers are of great importance to verify the long term stability of DLC
      coated load bearing implants in the human body. DLC coatings were deposited on
      articulating lumbar spinal disks made of CoCr28Mo6 biomedical implant alloy using
      a plasma-activated chemical vapor deposition (PACVD) process. As an adhesion
      promoting interlayer, tantalum films were deposited by magnetron sputtering. Wear
      tests of coated and uncoated implants were performed in physiological solution up
      to a maximum of 101 million articulation cycles with an amplitude of +/-2 degrees
      and -3/+6 degrees  in successive intervals at a preload of 1200 N. The implants
      were characterized by gravimetry, inductively coupled plasma optical emission
      spectrometry (ICP-OES) and cross section scanning electron microscopy (SEM)
      analysis. It is shown that DLC coated surfaces with uncontaminated tantalum
      interlayers perform very well and no corrosive or mechanical failure could be
      observed. This also holds true in tests featuring overload and third-body wear by
      cortical bone chips present in the bearing pairs. Regarding the interlayer
      tolerance towards interlayer contamination (oxygen), limits for initiation of
      potential failure modes were established. It was found that mechanical failure is
      the most critical aspect and this mode is hypothetically linked to the alpha-beta
      tantalum phase switch induced by increasing oxygen levels as observed by X-ray
      diffraction (XRD). It is concluded that DLC coatings are a feasible candidate for
      near zero wear articulations on implants, potentially even surpassing the
      performance of ceramic vs. ceramic. 

PMID- 24921708
TI  - MicroRNAs in brain metastases: potential role as diagnostics and therapeutics.
AB  - Brain metastases remain a daunting adversary that negatively impact patient
      survival. Metastatic brain tumors affect up to 45% of all cancer patients with
      systemic cancer and account for ~20% of all cancer-related deaths. A complex
      network of non-coding RNA molecules, microRNAs (miRNAs), regulate tumor
      metastasis. The brain micro-environment modulates metastatic tumor growth;
      however, defining the precise genetic events that promote metastasis in the brain
      niche represents an important, unresolved problem. Understanding these events
      will reveal disease-based targets and offer effective strategies to treat brain
      metastases. Effective therapeutic strategies based upon the biology of brain
      metastases represent an urgent, unmet need with immediate potential for clinical
      impact. Studies have demonstrated the ability of miRNAs to distinguish normal
      from cancerous cells, primary from secondary brain tumors, and correctly
      categorize metastatic brain tumor tissue of origin based solely on miRNA
      profiles. Interestingly, manipulation of miRNAs has proven effective in cancer
      treatment. With the promise of reduced toxicity, increased efficacy and
      individually directed personalized anti-cancer therapy, using miRNA in the
      treatment of metastatic brain tumors may prove very useful and improve patient
      outcome. In this review, we focus on the potential of miRNAs as diagnostic and
      therapeutic targets for the treatment of metastatic brain lesions. 

PMID- 24921710
TI  - The influence of a S-to-S bridge in diiron dithiolate models on the oxidation
      reaction: a mimic of the H(air)(ox) state of [FeFe]-hydrogenases.
AB  - Two-electron oxidation of a diiron complex (1) containing a bulky S-to-S bridge
      with an exocyclic carbonyl group affords [1(OH)](+), which replicates the
      coordination structure and electronic configuration of H(air)(ox), and the
      chemically reversible reaction between 1 and [1(OH)](+) mimics the bioprocess of
      interconversion of the inactive H(air)(ox) and the active Hred states of the
      [FeFe]-hydrogenases.

PMID- 24921711
TI  - Diffusion-based microfluidic PCR for "one-pot" analysis of cells.
AB  - Genetic analysis starting with cell samples often requires multi-step processing
      including cell lysis, DNA isolation/purification, and polymerase chain reaction
      (PCR) based assays. When conducted on a microfluidic platform, the compatibility
      among various steps often demands a complicated procedure and a complex device
      structure. Here we present a microfluidic device that permits a "one-pot"
      strategy for multi-step PCR analysis starting from cells. Taking advantage of the
      diffusivity difference, we replace the smaller molecules in the reaction chamber
      by diffusion while retaining DNA molecules inside. This simple scheme effectively
      removes reagents from the previous step to avoid interference and thus permits
      multi-step processing in the same reaction chamber. Our approach shows high
      efficiency for PCR and potential for a wide range of genetic analysis including
      assays based on single cells. 

PMID- 24921712
TI  - Postoperative glaucoma following infantile cataract surgery: an individual
      patient data meta-analysis.
AB  - IMPORTANCE: Infantile cataract surgery bears a significant risk for postoperative
      glaucoma, and no consensus exists on factors that may reduce this risk.
      OBJECTIVE: To assess the effect of primary intraocular lens implantation and
      timing of surgery on the incidence of postoperative glaucoma. DATA SOURCES: We
      searched multiple databases to July 14, 2013, to identify studies with eligible
      patients, including PubMed, MEDLINE, EMBASE, ISI Web of Science, Scopus, Central,
      Google Scholar, Intute, and Tripdata. We also searched abstracts of ophthalmology
      society meetings. STUDY SELECTION: We included studies reporting on postoperative
      glaucoma in infants undergoing cataract surgery with regular follow-up for at
      least 1 year. Infants with concurrent ocular anomalies were excluded. DATA
      EXTRACTION AND SYNTHESIS: Authors of eligible studies were invited to contribute
      individual patient data on infants who met the inclusion criteria. We also
      performed an aggregate data meta-analysis of published studies that did not
      contribute to the individual patient data. Data were pooled using a random
      effects model. MAIN OUTCOMES AND MEASURES: Time to glaucoma with the effect of
      primary implantation, additional postoperative intraocular procedures, and age at
      surgery. RESULTS: Seven centers contributed individual patient data on 470
      infants with a median age at surgery of 3.0 months and median follow-up of 6.0
      years. Eighty patients (17.0%) developed glaucoma at a median follow-up of 4.3
      years. Only 2 of these patients had a pseudophakic eye. The risk for
      postoperative glaucoma appeared to be lower after primary implantation (hazard
      ratio [HR], 0.10 [95% CI, 0.01-0.70]; P = .02; I(2) = 34%), higher after surgery
      at 4 weeks or younger (HR, 2.10 [95% CI, 1.14-3.84]; P = .02; I(2) = 0%), and
      higher after additional procedures (HR, 2.52 [95% CI, 1.11-5.72]; P = .03; I(2) =
      32%). In multivariable analysis, additional procedures independently increased
      the risk for glaucoma (HR, 2.25 [95% CI, 1.20-4.21]; P = .01), and primary
      implantation independently reduced it (HR, 0.10 [95% CI, 0.01-0.76]; P = .03).
      Results were similar in the aggregate data meta-analysis that included data from
      10 published articles. CONCLUSIONS AND RELEVANCE: Although confounding factors
      such as size of the eye and surgeon experience are not accounted for in this meta
      analysis, the risk for postoperative glaucoma after infantile cataract surgery
      appears to be influenced by the timing of surgery, primary implantation, and
      additional intraocular surgery.

PMID- 24921713
TI  - Face recognition in simulated prosthetic vision: face detection-based image
      processing strategies.
AB  - OBJECTIVE: Given the limited visual percepts elicited by current prosthetic
      devices, it is essential to optimize image content in order to assist implant
      wearers to achieve better performance of visual tasks. This study focuses on
      recognition of familiar faces using simulated prosthetic vision. APPROACH:
      Combined with region-of-interest (ROI) magnification, three face extraction
      strategies based on a face detection technique were used: the Viola-Jones face
      region, the statistical face region (SFR) and the matting face region. MAIN
      RESULTS: These strategies significantly enhanced recognition performance compared
      to directly lowering resolution (DLR) with Gaussian dots. The inclusion of
      certain external features, such as hairstyle, was beneficial for face
      recognition. Given the high recognition accuracy achieved and applicable
      processing speed, SFR-ROI was the preferred strategy. DLR processing resulted in
      significant face gender recognition differences (i.e. females were more easily
      recognized than males), but these differences were not apparent with other
      strategies. SIGNIFICANCE: Face detection-based image processing strategies
      improved visual perception by highlighting useful information. Their use is
      advisable for face recognition when using low-resolution prosthetic vision. These
      results provide information for the continued design of image processing modules
      for use in visual prosthetics, thus maximizing the benefits for future prosthesis
      wearers.

PMID- 24921715
TI  - Dispersion compensation by two-stage stretching in a sub-400 fs, 1.2 mJ Yb:CaF2
      amplifier.
AB  - We generate 1.24 mJ, 390 fs pulses at 1035 nm in a CPA laser system featuring a
      2.8 mJ Yb:CaF(2) regenerative amplifier, stretcher/compressor based on a single
      chirped volume Bragg grating and a compact, low-dispersion grating compressor.
      The auxiliary compressor is used to effectively pre-compensate the intra-cavity
      dispersion of the amplifier.

PMID- 24921714
TI  - The prevalence of COPD co-morbidities in Serbia: results of a national survey.
AB  - BACKGROUND: Research studies have found different prevalence rates for co
      morbidities in patients with chronic obstructive pulmonary disease (COPD). AIMS:
      The aim of our study was to investigate the prevalence of co-morbidities as well
      as functional limitations in subjects with COPD. METHODS: The study was based on
      a nationally representative sample of the population of Serbia. Information on
      the health of the population was obtained from interviews and anthropometric
      measurements. In this study we analysed a total of 10,013 respondents aged 40
      years or older. There were 653 subjects with COPD and 9,360 respondents without
      COPD. RESULTS: Out of the 10,013 respondents, 5,377 were aged 40-59 years and
      4,636 were 60 years or older. The prevalence of COPD was 5.0% in respondents aged
      40-59 years and 8.3% in those aged 60 years or older; the total prevalence was
      6.5%. The most prevalent co-morbidities among respondents with COPD were
      hypertension (54.5%) and dyslipidaemia (26.5%). The prevalence of all analysed co
      morbidities was higher in respondents with COPD and the difference was highly
      statistically significant, except for stroke and malignancies, for which the
      difference was significant. Analysis showed that respondents with COPD had a
      higher prevalence of all analysed clinical factors (dizziness, obesity, anaemia
      and frailty) and functional impairments (mobility and hearing and visual
      impairment) compared with respondents without COPD. For those aged 40-59 years
      the difference was highest for mobility difficulty (four times higher prevalence
      in COPD patients) and anaemia (three times higher in COPD patients). CONCLUSION:
      Our analysis showed that the most prevalent co-morbidities in COPD were
      hypertension, dyslipidaemia, chronic renal disease and anxiety/depression. The
      finding suggests that health professionals should actively assess co-morbidities
      in patients with COPD.

PMID- 24921716
TI  - Multimode regimes in quantum cascade lasers with optical feedback.
AB  - We study the instability thresholds of the stationary emission of a quantum
      cascade laser with optical feedback described by the Lang Kobayashi model. We
      introduce an exact linear stability analysis and an approximated one for an
      unipolar lasers, who does not exhibit relaxation oscillations, and investigate
      the regimes of the emitter beyond the continuous wave instability threshold,
      depending on the number and density of the external cavity modes. We then show
      that a unipolar laser with feedback can exhibit coherent multimode oscillations
      that indicate spontaneous phase-locking. 

PMID- 24921717
TI  - Multi-resolution imaging with an optimized number and distribution of sampling
      points.
AB  - We propose an approach of interest in Imaging and Synthetic Aperture Radar (SAR)
      tomography, for the optimal determination of the scanning region dimension, of
      the number of sampling points therein, and their spatial distribution, in the
      case of single frequency monostatic multi-view and multi-static single-view
      target reflectivity reconstruction. The method recasts the reconstruction of the
      target reflectivity from the field data collected on the scanning region in terms
      of a finite dimensional algebraic linear inverse problem. The dimension of the
      scanning region, the number and the positions of the sampling points are
      optimally determined by optimizing the singular value behavior of the matrix
      defining the linear operator. Single resolution, multi-resolution and dynamic
      multi-resolution can be afforded by the method, allowing a flexibility not
      available in previous approaches. The performance has been evaluated via a
      numerical and experimental analysis. 

PMID- 24921718
TI  - Enhancing optofluidic actuation of micro-objects by tagging with plasmonic
      nanoparticles.
AB  - We report experimentally and theoretically on the significant exaltation of
      optical forces on microparticles when they are partially coated by metallic
      nanodots and shined with laser light within the surface plasmon resonance.
      Optical forces on both pure silica particles and silica-gold raspberries are
      characterized using an optical chromatography setup to measure the variations of
      the Stokes drag versus laser beam power. Results are compared to the Mie theory
      prediction for both pure dielectric particles and core-shell ones with a shell
      described as a continuous dielectric-metal composite of dielectric constant
      determined from the Maxwell-Garnett approach. The observed quantitative agreement
      demonstrates that radiation pressure forces are directly related to the metal
      concentration on the microparticle surface and that metallic nanodots increase
      the magnitude of optical forces compared to pure dielectric particles of the same
      overall size, even at very low metal concentration. Behaving as "micro-sized
      nanoparticles", the benefit of microparticles coated with metallic nanodots is
      thus twofold: it significantly enhances optofluidic manipulation and motion at
      the microscale, and brings nanometric optical, chemical or biological
      capabilities to the microscale. 

PMID- 24921719
TI  - Damage morphology change condition and thermal accumulation effect on high
      reflection coatings at 1064nm.
AB  - The damage conversion behavior of high-reflection coatings under multiple shot of
      1064nm nanosecond pulse laser has been investigated. The mechanism of initiation
      and evolution law of multi-shot damage has been revealed by use of surface
      profiler and focus ion beam with SEM. The scald damage tends to become delaminate
      damage under some certain condition. Huge experiments supports that this
      morphology change condition has a close connection with scald initial fluence,
      scald size, subsequent fluence and shot number. The relationship among these
      factors is for the first time achieved to offer the "safety lines" for
      components. The thermal accumulation effect on the decline of damage threshold
      under multi-shot has been studied in theory and verified experimentally. In
      addition, a theory-based formula is used to fit the experiment data for further
      prediction of thin film life-time. 

PMID- 24921720
TI  - Complex, 3D modeling of the acousto-optical interaction and experimental
      verification.
AB  - The acousto-optical crystals are frequently used, indispensable elements of high
      technology and modern science, and yet their precise numerical description has
      not been available. In this paper an accurate, rapid and quite general model of
      the AO interaction in a Bragg-cell is presented. The suitability of the
      simulation is intended to be verified experimentally, for which we wanted to
      apply the most convincing measurement methods. The difficulty of the verification
      is that the measurement contains unknown parameters. Therefore we performed an
      elaborated series of measurements and developed a method for the estimation of
      the unknown parameters. 

PMID- 24921722
TI  - Temporal and spectral structure of the infrared pulse during the high order
      harmonic generation.
AB  - We present, for the first time, the complete pulse characterization of the
      infrared pulse after generating harmonics. A systematic study of the high
      harmonic generation process, and the generating infrared pulse characterization,
      has been done by changing the focus-gas-jet relative position. We have concluded,
      supported by nonlinear propagation simulations, that there is a correlation
      between the spectral and temporal nonlinear evolution of the infrared generating
      field and the structures shown in the harmonic signal. We have identified two
      different pressure regimes: the low pressure regime, characterized by the effects
      produced by the plasma generated by the infrared pulse, and the high pressure
      regime where the plasma and the Kerr effect generated by the infrared field are
      both present. These observations highlight the important role played by the
      nonlinear propagation of the generating field in the high harmonic generation
      context. 

PMID- 24921721
TI  - Simultaneous compression, characterization and phase stabilization of GW-level
      1.4 cycle VIS-NIR femtosecond pulses using a single dispersion-scan setup.
AB  - We have temporally characterized, dispersion compensated and carrier-envelope
      phase stabilized 1.4-cycle pulses (3.2 fs) with 160 uJ of energy at 722 nm using
      a minimal and convenient dispersion-scan setup. The setup is all inline, does not
      require interferometric beamsplitting, and uses components available in most
      laser laboratories. Broadband minimization of third-order dispersion using
      propagation in water enabled reducing the compressed pulse duration from 3.8 to
      3.2 fs with the same set of chirped mirrors. Carrier-envelope phase stabilization
      of the octave-spanning pulses was also performed by the dispersion-scan setup.
      This unprecedentedly simple and reliable approach provides reproducible CEP
      stabilized pulses in the single-cycle regime for applications such as CEP
      sensitive spectroscopy and isolated attosecond pulse generation. 

PMID- 24921723
TI  - Low threshold and high speed short cavity distributed feedback hybrid silicon
      lasers.
AB  - In this paper we investigate reducing threshold and improving the efficiency and
      speed of distributed feedback hybrid silicon lasers. A low threshold current of
      8.8 mA was achieved for a 200 MUm cavity at 20  degrees C. A 3 dB bandwidth of
      9.5 GHz as well as 12.5 Gb/s direct modulation of DFB laser diode was achieved on
      the hybrid silicon platform for the first time. 

PMID- 24921724
TI  - Real-time integral imaging system for light field microscopy.
AB  - We propose a real-time integral imaging system for light field microscopy
      systems. To implement a 3D live in-vivo experimental environment for multiple
      experimentalists, we generate elemental images for an integral imaging system
      from the captured light field with a light field microscope in real-time. We
      apply the f-number matching method to generate an elemental image to reconstruct
      an undistorted 3D image. Our implemented system produces real and orthoscopic 3D
      images of micro objects in 16 frames per second. We verify the proposed system
      via experiments using Caenorhabditis elegans. 

PMID- 24921725
TI  - Parallel excitation-emission multiplexed fluorescence lifetime confocal
      microscopy for live cell imaging.
AB  - We present a novel excitation-emission multiplexed fluorescence lifetime
      microscopy (FLIM) method that surpasses current FLIM techniques in multiplexing
      capability. The method employs Fourier multiplexing to simultaneously acquire
      confocal fluorescence lifetime images of multiple excitation wavelength and
      emission color combinations at 44,000 pixels/sec. The system is built with low
      cost CW laser sources and standard PMTs with versatile spectral configuration,
      which can be implemented as an add-on to commercial confocal microscopes. The
      Fourier lifetime confocal method allows fast multiplexed FLIM imaging, which
      makes it possible to monitor multiple biological processes in live cells. The low
      cost and compatibility with commercial systems could also make multiplexed FLIM
      more accessible to biological research community. 

PMID- 24921726
TI  - Accuracy improvement of quantitative analysis in laser-induced breakdown
      spectroscopy using modified wavelet transform.
AB  - A modified algorithm of background removal based on wavelet transform was
      developed for spectrum correction in laser-induced breakdown spectroscopy (LIBS).
      The optimal type of wavelet function, decomposition level and scaling factor
      gamma were determined by the root-mean-square error of calibration (RMSEC) of the
      univariate regression model of the analysis element, which is considered as the
      optimization criteria. After background removal by this modified algorithm with
      RMSEC, the root-mean-square error of cross-validation (RMSECV) and the average
      relative error (ARE) criteria, the accuracy of quantitative analysis on chromium
      (Cr), vanadium (V), cuprum (Cu), and manganese (Mn) in the low alloy steel was
      all improved significantly. The results demonstrated that the algorithm developed
      is an effective pretreatment method in LIBS to significantly improve the accuracy
      in the quantitative analysis. 

PMID- 24921727
TI  - Flexible graphene saturable absorber on two-layer structure for tunable mode
      locked soliton fiber laser.
AB  - Using a two-layer structure consisting of polyethylene terephthalate (PET) and
      polydimethylsiloxane (PDMS) to support graphene grown by chemical vapor
      deposition (CVD), we demonstrate a flexible integrated graphene saturable
      absorber (SA) on microfiber for passive mode-locked soliton fiber laser. This
      method can optimize the light-graphene interaction by using evanescent field in
      the integration structure. Moreover, the fiber laser with the in-line microfiber
      to-graphene SA can realize the tunabilities of both the 3dB bandwidth of output
      optical spectrum and the pulse width of soliton. This tunable mode-locked soliton
      laser has potential applications in optical communication, optical microscopy,
      and so on. 

PMID- 24921728
TI  - High power Yb-Raman combined nonlinear fiber amplifier.
AB  - We demonstrated a high power Yb-Raman combined nonlinear fiber amplifier. The
      seed is a 30 W dual-wavelength Yb-doped fiber laser formed by 1070 nm and 1120 nm
      lasers. The gain medium in the amplifier stage is a 45-meters-long Yb-doped
      fiber, which power scaled the 1070 nm laser and Raman amplified the 1120 nm laser
      simultaneously. A record 1120 nm power of 732 W is obtained with pump power of
      890 W. Numerical study taking into account of both Yb and Raman gain has been
      conducted to analyze the output characters and power evolution in the amplifier
      under different conditions. The numerical results are in good agreement with the
      experiment. This amplifier is also suitable to amplify laser in the wavelength
      range of 1100-1150 nm. 

PMID- 24921729
TI  - Unrepeatered 256 Gb/s PM-16QAM transmission over up to 304 km with simple system
      configurations.
AB  - We study unrepeatered transmission of 40x256 Gb/s systems with polarization
      multiplexed 16-quadrature amplitude modulation (PM-16QAM) channels using simple
      coherent optical system configurations. Three systems are investigated with
      either a homogeneous fiber span, or simple two-segment hybrid fiber designs. Each
      system relies primarily on ultra-low loss, very large effective area fiber, while
      making use of only first-order backward pumped Raman amplification and no remote
      optically pumped amplifier (ROPA). For the longest span studied, we demonstrate
      unrepeatered 256 Gb/s transmission over 304 km with the additional aid of
      nonlinear compensation using digital backpropagation. We find an average
      performance improvement in terms of the Q-factor of 0.45 dB by using digital
      backpropagation compared to the case of using chromatic dispersion compensation
      alone for an unrepeatered span system. 

PMID- 24921730
TI  - Novel wavelength conversion with nanophotonic droplet consisting of coupled
      quantum dots.
AB  - The concept of nanophotonic droplets, which are individual spherical polymer
      structures containing accurately coupled heterogeneous quantum dots, has been
      previously demonstrated. Such combinations are theoretically promising for their
      ability to induce novel optical functions. In this paper, we focus on the
      implementation of wavelength conversion as one of the fundamental optical
      functions of nanophotonic droplets. A novel mechanism involved in the formation
      of nanophotonic droplets and results of experimental verification of wavelength
      conversion using formed nanophotonic droplets are described. By a quantitative
      comparison with a corresponding sample consisting of randomly dispersed quantum
      dots, the effectiveness of proposal was successfully demonstrated. 

PMID- 24921731
TI  - High-frequency extinction efficiencies of spheroids: rigorous T-matrix solutions
      and semi-empirical approximations.
AB  - A semi-empirical high-frequency formula is developed to efficiently and
      accurately compute the extinction efficiencies of spheroids in the cases of
      moderate and large size parameters under either fixed or random orientation
      condition. The formula incorporates the semi-classical scattering concepts
      formulated by extending the complex angular momentum approximation of the Lorenz
      Mie theory to the spheroid case on the basis of the physical rationales
      associated with changing the particle morphology from a sphere to a spheroid. The
      asymptotic edge-effect expansion is truncated with an optimal number of terms
      based on a priori knowledge obtained from comparing the semi-classical Mie
      extinction efficiencies with the Lorenz-Mie solutions. The present formula is
      fully tested in comparison with the T-matrix results for spheroids with the
      aspect ratios from 0.5 to 2.0, and for various refractive indices m(r) + im(i),
      with m(r) from 1.0 to 2.0 and m(i) from 0 to 0.5.

PMID- 24921732
TI  - Observations of artefacts in the x-ray ptychography method.
AB  - X-ray ptychography, a scanning coherent diffraction imaging method, was used to
      reconstruct images of a "Siemens star" test pattern with amplitude and phase
      contrast. While studying how the use of illumination with an increased bandwidth
      results in clear improvements in the quality of image reconstructions, we found
      that an artificial change in the overall distance scale factor of the algorithm
      leads to a systematic response in the image, which is reproduced with an
      incorrect number of spokes. This pathology is explained by the conflict between
      the length scales set by the scan and by the diffraction patterns on the
      detector. 

PMID- 24921733
TI  - Cubic B-spline calibration for 3D super-resolution measurements using astigmatic
      imaging.
AB  - In recent years three-dimensional (3D) super-resolution fluorescence imaging by
      single-molecule localization (localization microscopy) has gained considerable
      interest because of its simple implementation and high optical resolution.
      Astigmatic and biplane imaging are experimentally simple methods to engineer a 3D
      specific point spread function (PSF), but existing evaluation methods have proven
      problematic in practical application. Here we introduce the use of cubic B
      splines to model the relationship of axial position and PSF width in the above
      mentioned approaches and compare the performance with existing methods. We show
      that cubic B-splines are the first method that can combine precision, accuracy
      and simplicity. 

PMID- 24921734
TI  - Rayleigh scattering of surface plasmons by sub-wavelength holes.
AB  - We study the scattering of surface plasmons from sub-wavelength holes and find
      that it exhibits a stronger wavelength dependence than the traditional lambda(-4)
      scaling found for Rayleigh scattering of light from small particles. This
      experimental observation is consistent with recent theoretical work and linked to
      the two-dimensional nature of the surface plasmon and the wavelength dependence
      of its spatial extent in the third dimension. The scattering cross sections are
      obtained with a frequency-correlation technique, which compares intensity speckle
      patterns observed behind various random structures of holes and recorded at
      different wavelengths. This powerful technique even allows us to distinguish
      between scattering of surface plasmons into photons and scattering into other
      surface plasmons.

PMID- 24921735
TI  - A polarization-sensitive 4-contact detector for terahertz time-domain
      spectroscopy.
AB  - A light polarization angle-sensitive photoconductive detector for terahertz time
      domain spectroscopy is computer-modeled, microfabricated, and tested. The
      experimental results show good agreement with the linear angular response for an
      ideal detector. The detector's frequency, angular, and crosstalk responses are
      discussed in the context of theoretical and experimental considerations. 

PMID- 24921736
TI  - Nanofocusing in circular sector-like nanoantennas.
AB  - Gold circular sector-like nanoantennas (with a radius of 500 nm and a taper angle
      of 60 degrees , 90 degrees , and 120 degrees ) on glass are investigated in a
      near-infrared wavelength range (900 - 2100 nm). Amplitude- and phase-resolved
      near-field images of circular sector-like antenna modes at telecom wavelength
      feature a concentric circular line of phase contrast, demonstrating resonant
      excitation of a standing wave of counter-propagating surface plasmons, travelling
      between a tip and opposite circular edge of the antenna. Transmission spectra
      obtained in the range 900 - 2100 nm are in good agreement with numerical
      simulations, revealing the main feature of this antenna configuration, viz., the
      resonance wavelength, in contrast to triangular antennas, does not depend on the
      taper angle and is determined only by the sector radius. This feature together
      with a robust and easily predictable frequency response makes circular sector
      like nanoantennas very promising for implementing bowtie antennas and attractive
      for many applications. 

PMID- 24921737
TI  - Generation of FCC-compliant and background-free millimeter-wave ultrawideband
      signal based on nonlinear polarization rotation in a highly nonlinear fiber.
AB  - We propose a novel approach to generating millimeter-wave (MMW) ultrawideband
      (UWB) signal based on nonlinear polarization rotation (NPR) in a highly nonlinear
      fiber (HNLF). The MMW UWB signal is background-free by eliminating the baseband
      frequency components using an optical filter. The proposed scheme is
      theoretically analyzed and experimentally verified. The generated MMW UWB signal
      centered at 25.5 GHz has a 10-dB bandwidth of 7 GHz from 22 to 29 GHz, which
      fully satisfies the spectral mask regulated by the Federal Communications
      Commission (FCC). 

PMID- 24921738
TI  - 800 Gb/s (80 * 10 Gb/s) capacity WDM-PON based on ASE injection seeding.
AB  - We demonstrate and characterize 800 Gb/s capacity WDM-PON with an ASE injection
      seeding. Required total seed power at central office to feeder fiber is 16 dBm
      for 20 km upstream transmission of 80 channels. We investigate the maximum
      transmission length according to channels. The transmission length is limited to
      39.7 km by intra-channel crosstalk induced by Rayleigh back-scattering, provided
      that the dispersion is compensated. Also, we investigate the allowable
      differential path length to evaluate the flexibility of the system. 

PMID- 24921739
TI  - Characterization and application of chirped photonic crystal fiber in multiphoton
      imaging.
AB  - Fiber delivery of ultrashort pulses is important for multiphoton endoscopy. A
      chirped photonic crystal fiber (CPCF) is first characterized for its transmission
      bandwidth, propagation loss, and dispersion properties. Its extremely low
      dispersion (~150 fs(2)/m) enables the delivery of sub-30 fs pulses through a ~1 m
      long CPCF. The CPCF is then incorporated into a multiphoton imaging system and
      its performance is demonstrated by imaging various biological samples including
      yew leaf, mouse tendon, and human skin. The imaging quality is further compared
      with images acquired by a multiphoton imaging system with free-space or hollow
      core photonic band-gap fiber (PBF) delivery of pulses. Compared with free-space
      system, the CPCF delivered system maintains the same ultrashort pulsewidth and
      the image qualities are comparable. Compared with the PBF delivery, CPCF provides
      a 35 times shorter pulsewidth at the sample location, which results in a ~12 and
      50 times improvement in two-photon excitation fluorescence (TPEF) and second
      harmonic generation (SHG) signals respectively. Our results show that CPCF has
      great potential for fiber delivery of ultrashort pulses for multiphoton
      endoscopy.

PMID- 24921740
TI  - Absolute distance measurement by intensity detection using a mode-locked
      femtosecond pulse laser.
AB  - We propose an interferometric method that enables to measure a distance by the
      intensity measurement using the scanning of the interferometer reference arm and
      the recording of the interference fringes including the brightest fringe. With
      the consideration of the dispersion and absorption of the pulse laser in a
      dispersive and absorptive medium, we investigate the cross-correlation function
      between two femtosecond laser pulses in the time domain. We also introduce the
      measurement principle. We study the relationship between the position of the
      brightest fringe and the distance measured, which can contribute to the distance
      measurement. In the experiments, we measure distances using the method of the
      intensity detection while the reference arm of Michelson interferometer is
      scanned and the fringes including the brightest fringe is recorded. Firstly we
      measure a distance in a range of 10 um. The experimental results show that the
      maximum deviation is 45 nm with the method of light intensity detection.
      Secondly, an interference system using three Michelson interferometers is
      developed, which combines the methods of light intensity detection and time-of
      flight. This system can extend the non-ambiguity range of the method of light
      intensity detection. We can determine a distance uniquely with a larger non
      ambiguity range. It is shown that this method and system can realize absolute
      distance measurement, and the measurement range is a few micrometers in the
      vicinity of Nl(pp), where N is an integer, and lpp is the pulse-to-pulse length.

PMID- 24921741
TI  - Common-path diffraction optical tomography for investigation of three-dimensional
      structures and dynamics of biological cells.
AB  - We present an optical holographic micro-tomographic technique for imaging both
      the three-dimensional structures and dynamics of biological cells. Optical light
      field images of a sample, illuminated by a plane wave with various illumination
      angles, are measured in a common-path interferometry, and thus both the three
      dimensional refractive index tomogram and two-dimensional dynamics of live
      biological cells are measured with extremely high sensitivity. The applicability
      of the technique is demonstrated through quantitative and measurements of
      morphological, chemical, and mechanical parameters at the individual cell level. 

PMID- 24921742
TI  - Towards 100 channel dense wavelength division multiplexing with 100GHz spacing on
      silicon.
AB  - A 1 by 4 wavelength division multiplexer with 0.5nm bandwidth and no free
      spectral range limitation is demonstrated on silicon. The device utilizes wide
      bandwidth filters cascaded with ring resonators in order to select specific ring
      resonator modes and route each resonant mode to a separate port. This technology
      will enable dense wavelength division multiplexing covering the C - and L - bands
      with up to 100 10GB/s channels separated by 100GHz to be implemented for optical
      interconnects applications. A 1 by 4 wavelength division multiplexer with 3dB
      channel bandwidths as small as 0.5nm and 1dB insertion loss are demonstrated with
      16dB inter-channel crosstalk suppression. A second wavelength division
      multiplexer scheme with four channels, each spaced 0.5nm apart without any free
      spectral range limitations is also demonstrated using wide bandwidth filters
      centered at the same wavelength to select resonances from four different ring
      resonators with slightly different widths. 

PMID- 24921743
TI  - Electronically resonant third-order sum frequency generation spectroscopy using a
      nanosecond white-light supercontinuum.
AB  - Third-order sum frequency generation (TSFG) is one of the third-order nonlinear
      optical processes, and has the generation mechanism analogous to third harmonic
      generation (THG). By using a white-light supercontinuum, we can obtain broadband
      multiplex TSFG spectra. In the present study, we developed an electronically
      resonant TSFG spectrometer, and applied it to obtain TSFG spectra of
      hemoproteins. Analyzed TSFG ratio spectra clearly showed the resonant enhancement
      attributable to the electronic state of hemoproteins. This is a promising method
      for the imaging of electronic states of molecules inside living cells or tissues.

PMID- 24921744
TI  - Embedded coupled microrings with high-finesse and close-spaced resonances for
      optical signal processing.
AB  - Single microring resonators have been used in applications such as wavelength
      multicasting and microwave photonics, but the dependence of the free spectral
      range with ring radius imposes a trade-off between the required GHz optical
      channel spacing, footprint and power consumption. We demonstrate four-channel all
      optical wavelength multicasting using only 1 mW of control power, with converted
      channel spacing of 40-60 GHz. Our device is based on a compact embedded microring
      design fabricated on a scalable SOI platform. The coexistence of close resonance
      spacing and high finesse (205) in a compact footprint is possible due to enhanced
      quality factors (30,000) resulting from the embedded configuration and the
      coupling-strength dependence of resonance spacing, instead of ring size. In
      addition, we discuss the possibility of achieving continuously mode splitting
      from a single-notch resonance up to 40 GHz. 

PMID- 24921745
TI  - Spiral-structured fiber Bragg grating for contact force sensing through direct
      power measurement.
AB  - A high-sensitivity fiber Bragg grating (FBG) force sensor based on direct optical
      power measurement is presented. The approach utilizes a novel structure where the
      FBG is mounted on a thin tube-like fixture spirally. Contact force measurement is
      achieved through direct measurement of the FBG reflection power at a single
      wavelength using a power meter. The measuring system in our approach is simple
      and does not require processing of massive amount of spectral data, enabling real
      time contact force monitoring. When force is applied to the FBG sensor, the
      unique spiral structure leads to FBG chirping and reflection spectrum broadening.
      A proportional relationship and linear fit are found between the force applied
      (up to 1.55 N) and the optical power reflected by the proposed FBG sensor. An
      average sensitivity of 11.16 dB/N is experimentally achieved. This design
      significantly reduces system complexity and improves data processing speed, which
      has great practical value in real-time FBG sensing applications. 

PMID- 24921746
TI  - A pseudo-planar metasurface for a polarization rotator.
AB  - New demonstrations of effective interaction between light and artificially
      electromagnetic interface, or the metasurface, have stimulated intensive research
      interests on control of light to realize applications in beam steering, optical
      imaging and light focusing, etc. Here we reported a new type of planar
      metasurface of which every individual metamolecule is single metallic layer with
      stereo structure and the metasurface is name as Pseudo-Planar Metasurface (PPM).
      The metamolecule of the PPM is a chiral structure and therefore derives
      significant optical activity. 

PMID- 24921747
TI  - Experimental demonstrations of dual polarization CO-OFDM using mid-span spectral
      inversion for nonlinearity compensation.
AB  - We experimentally demonstrate fiber nonlinearity compensation in dual
      polarization coherent optical OFDM (DP CO-OFDM) systems using mid-span spectral
      inversion (MSSI). We use third-order nonlinearity between a pump and the signal
      in a highly nonlinear fiber (HNLF) for MSSI. Maximum launch powers at FEC
      threshold for two 10 * 80-km 16-QAM OFDM systems were increased by 6.4 dB at a
      121-Gb/s data rate and 2.8 dB at 1.2 Tb/s. The experimental results are the first
      demonstration of using MSSI for nonlinearity compensation in any dual
      polarization coherent system. Simulations show that these increases could support
      a 22% increase in total transmission distance at 1.2-Tb/s system without
      increasing the number of inline amplifiers, by extending the fiber spans from 90
      to 110 km. When spans of 80 km are used, simulations reveal that MSSI system
      performance shows less degradation with increasing transmission distance, and an
      overall transmission distance increase of more than 70% is expected using MSSI. 

PMID- 24921748
TI  - Novel method for quantifying the cell size of marine phytoplankton based on
      optical measurements.
AB  - Phytoplankton size is important for the pelagic food web and oceanic ecosystems.
      However, the size of phytoplankton is difficult to quantify because of
      methodological constraints. To address this limitation, we have exploited the
      phytoplankton package effect to develop a new method for estimating the mean cell
      size of individual phytoplankton populations. This method was validated using a
      data set that contained simultaneous measurements of phytoplankton absorption and
      cell size distributions from 13 phytoplankton species. Comparing with existing
      methods, our method is more efficient with good accuracy, and it could
      potentially be applied in current in situ optical instruments. 

PMID- 24921749
TI  - Optical signal to noise ratio improvement through unbalanced noise beating in
      phase-sensitive parametric amplifiers.
AB  - We investigate the beating of signal and idler waves, which have imbalanced
      signal to noise ratios, in a phase-sensitive parametric amplifier. Imbalanced
      signal to noise ratios are achieved in two ways; first by imbalanced noise
      loading; second by varying idler to signal input power ratio. In the case of
      imbalanced noise loading the phase-sensitive amplifier improved the signal to
      noise ratio from 3 to 6 dB, and in the case of varying idler to signal input
      power ratio, the signal to noise ratio improved from 3 to in excess of 20 dB. 

PMID- 24921750
TI  - Efficient, compact and low loss thermo-optic phase shifter in silicon.
AB  - We design a resistive heater optimized for efficient and low-loss optical phase
      modulation in a silicon-on-insulator (SOI) waveguide and characterize the
      fabricated devices. Modulation is achieved by flowing current perpendicular to a
      new ridge waveguide geometry. The resistance profile is engineered using
      different dopant concentrations to obtain localized heat generation and maximize
      the overlap between the optical mode and the high temperature regions of the
      structure, while simultaneously minimizing optical loss due to free-carrier
      absorption. A 61.6 MUm long phase shifter was fabricated in a CMOS process with
      oxide cladding and two metal layers. The device features a phase-shifting
      efficiency of 24.77 +/- 0.43 mW/pi and a -3 dB modulation bandwidth of 130.0 +/-
      5.59 kHz; the insertion loss measured for 21 devices across an 8-inch wafer was
      only 0.23 +/- 0.13 dB. Considering the prospect of densely integrated photonic
      circuits, we also quantify the separation necessary to isolate thermo-optic
      devices in the standard 220 nm SOI platform. 

PMID- 24921751
TI  - (87)Rb-stabilized 375-MHz Yb:fiber femtosecond frequency comb.
AB  - We report a fully stabilized 1030-nm Yb-fiber frequency comb operating at a pulse
      repetition frequency of 375 MHz. The comb spacing was referenced to a Rb
      stabilized microwave synthesizer and the comb offset was stabilized by generating
      a super-continuum containing a coherent component at 780.2 nm which was
      heterodyned with a (87)Rb-stabilized external cavity diode laser to produce a
      radio-frequency beat used to actuate the carrier-envelope offset frequency of the
      Yb-fiber laser. The two-sample frequency deviation of the locked comb was 235 kHz
      for an averaging time of 50 seconds, and the comb remained locked for over 60
      minutes with a root mean squared deviation of 236 kHz.

PMID- 24921752
TI  - Construction model for total variation regularization parameter.
AB  - Image denoising is important for high-quality imaging in adaptive optics.
      Richardson-Lucy deconvolution with total variation(TV) regularization is commonly
      used in image denoising. The selection of TV regularization parameter is an
      essential issue, yet no systematic approach has been proposed. A construction
      model for TV regularization parameter is proposed in this paper. It consists of
      four fundamental elements, the properties of which are analyzed in details. The
      proposed model bears generality, making it apply to different image recovery
      scenarios. It can achieve effective spatially adaptive image recovery, which is
      reflected in both noise suppression and edge preservation. Simulations are
      provided as validation of recovery and demonstration of convergence speed and
      relative mean-square error. 

PMID- 24921753
TI  - Highly controllable synthesis of near-infrared persistent luminescence
      SiO2/CaMgSi2O6 composite nanospheres for imaging in vivo.
AB  - High quality near-infrared (NIR) persistent luminescence nanospheres (PLNPs) were
      synthesized using a simple mesoporous template method. The as-synthesized NIR
      persistent luminescence nanoparticles have uniform spherical morphology, tunable
      sizes, and a nominal composition of SiO(2)/CaMgSi(2)O(6):Eu(2+), Pr(3+), Mn(2+)
      (denoted as SEPM). Their NIR persistent luminescence at 660 nm can be detected
      during more than 1 hour. The in vivo distribution of the nanoparticles in the
      abdomen can be detected in real time after injection into the abdomen of a mouse.
      The nanoparticles can be metabolized from the lymph circulation and transferred
      from the abdomen to the bladder. The results indicate an effective method to
      offer high quality NIR persistent luminescence nanoprobes for imaging.

PMID- 24921755
TI  - High-power mid-infrared frequency comb from a continuous-wave-pumped bulk optical
      parametric oscillator.
AB  - We demonstrate that it is possible to obtain a mid-infrared optical frequency
      comb (OFC) experimentally by using a continuous-wave-pumped optical parametric
      oscillator (OPO). The comb is generated without any active modulation. It is
      based on cascading quadratic nonlinearities that arise from intra-cavity phase
      mismatched second harmonic generation of the signal wave that resonates in the
      OPO. The generated OFC is transferred from the signal wavelength (near-infrared)
      to the idler wavelength (mid-infrared) by intracavity difference frequency
      generation between the OPO pump wave and the signal comb. We have produced a mid
      infrared frequency comb which is tunable from 3.0 to 3.4 um with an average
      output power of up to 3.1 W. 

PMID- 24921754
TI  - Pulsed quantum cascade laser based hypertemporal real-time headspace
      measurements.
AB  - Optical cavity enhancement is a highly desirable process to make sensitive direct
      absorption spectroscopic measurements of unknown substances, such as explosives,
      illicit material, or other species of interest. This paper reports advancements
      in the development of real-time cavity ringdown spectroscopy over a wide
      bandwidth, with the aim to make headspace measurements of molecules at trace
      levels. We report results of two pulsed quantum cascade systems operating between
      (1200 to 1320)cm(-1) and (1316 to 1613)cm(-1) that measure the headspace of
      nitromethane, acetonitrile, acetone, and nitroglycerin, where the spectra are
      obtained in less than four seconds and contain at least 150,000 spectral
      wavelength datapoints.

PMID- 24921756
TI  - First demonstration of a 2MUm few-mode TDFA for mode division multiplexing.
AB  - We report the first demonstration of an inline few-mode thulium doped fiber
      amplifier (TDFA) operating at 2MUm for mode division multiplexed transmission.
      Similar gain and noise figure performance for both the LP(01) and LP(11) modes
      are obtained in a cladding pumped 2-mode group TDFA. A maximum gain of 18.3dB was
      measured at 1970nm with a 3dB gain bandwidth of 75nm while the average noise
      figure was measured to be between 7 and 8dB for wavelengths longer than 1970nm.

PMID- 24921757
TI  - Integrated silicon modulator based on microring array assisted MZI.
AB  - A silicon modulator with microring array assisted MZI is experimentally
      demonstrated on silicon-on-insulator wafer through CMOS-compatible process. The
      footprint of the whole modulator is about 600 MUm(2). With forward-biased current
      driven p-n junction, the 3-dB modulation bandwidth is ~2GHz. Furthermore, the
      impact of ambient temperature is minified with the help of MZI. Within
      temperature range of 10 - 70  degrees C, the maximum divergence of modulation
      curve is less than ~3 dB.

PMID- 24921758
TI  - Transmission-lattice based geometric phase analysis for evaluating the dynamic
      deformation of a liquid surface.
AB  - Quantitatively measuring a dynamic liquid surface often presents a challenge due
      to high transparency, fluidity and specular reflection. Here, a novel
      Transmission-Lattice based Geometric Phase Analysis (TLGPA) method is introduced.
      In this method, a special lattice is placed underneath a liquid to be tested and,
      when viewed from above, the phase of the transmission-lattice image is modulated
      by the deformation of the liquid surface. Combining this with multi-directional
      Newton iteration algorithms, the dynamic deformation field of the liquid surface
      can be calculated from the phase variation of a series of transmission-lattice
      images captured at different moments. The developed method has the advantage of
      strong self-adaption ability to initial lattice rotational errors and this is
      discussed in detail. Dynamic 3D ripples formation and propagation was
      investigated and the results obtained demonstrated the feasibility of the method.

PMID- 24921759
TI  - Thermal management in hybrid InP/silicon photonic crystal nanobeam laser.
AB  - Thermal properties of InP-based quantum well photonic crystal nanobeam lasers
      heterogeneously integrated on silicon on insulator waveguides are studied. We
      show both numerically and experimentally the reduction of the thermal resistance
      of the III-V cavities by adjusting the composition of the layer which bonds the
      III-V materials to the silicon wafer and by adding an over-cladding on top of the
      cavities. Using a bonding layer made of benzocyclobutene and SiO(2) and an over
      cladding of MgF(2), we found a decrease by a factor higher than 35 compared to
      air-suspended photonic crystal nanobeam cavities. Such optimized structures are
      demonstrated to operate under continuous wave pumping for several 10's of minutes
      despite the adverse effect of non-radiative surface recombination of carriers.

PMID- 24921760
TI  - Analytical modeling of XPM in dispersion-managed coherent fiber-optic systems.
AB  - An analytical model for the cross-phase modulation (XPM) variance in dispersion
      managed coherent fiber-optic systems is developed based on the first order
      perturbation theory. The XPM variance is analytically calculated for arbitrary
      pulse shapes. For a non-Gaussian pulse, the summation of time-shifted Gaussian
      pulses is used to fit the target pulse shape, which not only provides a good
      approximation of the non-Gaussian pulse but also allows explicit derivation of
      the XPM variance. The analytically estimated XPM variance is found to be in good
      agreement with numerical simulations. 

PMID- 24921761
TI  - Apertureless beam pen lithography based on fully metal-coated polyurethane
      acrylate (PUA) pyramidal microstructure array.
AB  - This work demonstrates a form of arrayed transmitting apertureless near-field
      photolithography, called apertureless beam pen lithography. An array of fully
      chromium-coated polyurethane acrylate (PUA) pyramidal microstructures was
      illuminated by a traditional Ultraviolet (UV) lamp to generate an array of
      massive UV beam pens for realizing apertureless beam pen lithography.
      Experimental results reveal that significant UV energy can pass through the apex
      of a fully metal-coated PUA pyramid even though the thickness of the metallic
      coating exceeded the penetration depth. The patterned photoresist profiles were
      117 nm deep and the full-width-at-half-magnitude (FWHM) was 180 nm when the
      exposure dosage was 54 mJ/cm(2) and the wavelength was 365 nm. Both depth and
      FWHM increased with exposure dosage, implying that the profiles depended on
      exposure dosage rather than on physical imprinting. With the adjustment of the
      thickness of the photoresist layer and the exposure parameters, the lift-off
      process yields arrayed metal dots with a diameter of 300 nm. Finite-element
      simulation of the intensity distribution near the apex of the pyramid and within
      the photoresist layer was carried out to reveal that the energy concentration
      within the pyramids is increased by approximately an order of magnitude,
      significantly enhancing the UV energy that passes through the fully metal-coated
      apex. The contrast curve model of the photoresist was used to calculate the
      patterned photoresist profiles for various energies. Experimental results,
      theoretical analysis and potential improvements of the method are presented.

PMID- 24921762
TI  - Asymmetric double-image encryption based on cascaded discrete fractional random
      transform and logistic maps.
AB  - A double-image encryption is proposed based on the discrete fractional random
      transform and logistic maps. First, an enlarged image is composited from two
      original images and scrambled in the confusion process which consists of a number
      of rounds. In each round, the pixel positions of the enlarged image are relocated
      by using cat maps which are generated based on two logistic maps. Then the
      scrambled enlarged image is decomposed into two components. Second, one of two
      components is directly separated into two phase masks and the other component is
      used to derive the ciphertext image with stationary white noise distribution by
      using the cascaded discrete fractional random transforms generated based on the
      logistic map. The cryptosystem is asymmetric and has high resistance against to
      the potential attacks such as chosen plaintext attack, in which the initial
      values of logistic maps and the fractional orders are considered as the
      encryption keys while two decryption keys are produced in the encryption process
      and directly related to the original images. Simulation results and security
      analysis verify the feasibility and effectiveness of the proposed encryption
      scheme. 

PMID- 24921763
TI  - Random sources for optical frames.
AB  - Analytical models for random sources producing far fields with frame-like
      intensity profiles are introduced. The frames can have polar and Cartesian
      symmetry and adjustable sharpness of the inner and outer edges. The frames are
      shape invariant throughout the far zone but expand due to diffraction with
      growing distance from the source. The generalization to multiple nested frames is
      also discussed. The applications of the frames are envisioned in material surface
      processing and particle trapping. 

PMID- 24921764
TI  - Effects of three-dimensional polymer networks in vertical alignment liquid
      crystal display controlled by in-plane field.
AB  - Polymer network in vertical alignment liquid crystal cell driven by in-plane
      field (VA-IPS) is formed in three dimensions to achieve fast response time and to
      keep the liquid crystal alignment even when an external pressure is applied to
      the cell. The network formed by UV irradiation to vertically aligned liquid
      crystal cell with reactive mesogen does not disturb a dark state while exhibiting
      very fast decaying response time less than 2ms in all grey scales and almost zero
      pooling mura. The proposed device has a strong potential to be applicable to
      field sequential display owing to super-fast response time and flexible display
      owing to polymer network in bulk which supports a gap between two substrates. 

PMID- 24921765
TI  - External cavity diode lasers with 5kHz linewidth and 200nm tuning range at
      1.55MUm and methods for linewidth measurement.
AB  - Two simple external cavity diode laser designs using fibre pigtailed gain chips
      are tested and their properties compared with a high end DBR fibre laser. These
      ECDLs demonstrate a FWHM linewidth as low as 5.2kHz with a fitted Lorentzian FWHM
      linewidth as low as 1.6kHz. Tuning ranges of 200nm covering 1420nm to 1620nm were
      demonstrated. To the best of our knowledge these are the narrowest linewidth and
      most broadly tunable external cavity diode lasers reported to date. The
      improvement in linewidth is attributed to greatly enhanced acoustic isolation
      allowed by using fiber coupled gain chips and by replacing kinematic mounts with
      a pair of rotatable wedges for cavity alignment which eliminates acoustic
      resonances. A detailed description and discussion of techniques used to
      characterize the frequency noise and linewidths of these lasers is provided. 

PMID- 24921766
TI  - Erbium-doped waveguide DBR and DFB laser arrays integrated within an ultra-low
      loss Si3N4 platform.
AB  - Record low optical threshold power and high slope efficiency are reported for
      arrays of distributed Bragg reflector lasers integrated within an ultra-low-loss
      Si(3)N(4) planar waveguide platform. Additionally, arrays of distributed feedback
      laser designs are presented that show improvements in pump-to-signal conversion
      efficiency of over two orders of magnitude beyond that found in previously
      published devices. Lithographically defined sidewall gratings provide the
      required lasing feedback for both cavity configurations. Lasing emission is shown
      over a wide wavelength range (1534 to 1570 nm), with output powers up to 2.1 mW
      and side mode suppression ratios in excess of 50 dB.

PMID- 24921767
TI  - Transport of Intensity phase imaging by intensity spectrum fitting of
      exponentially spaced defocus planes.
AB  - We propose an alternative method for solving the Transport of Intensity equation
      (TIE) from a stack of through-focus intensity images taken by a microscope or
      lensless imager. Our method enables quantitative phase and amplitude imaging with
      improved accuracy and reduced data capture, while also being computationally
      efficient and robust to noise. We use prior knowledge of how intensity varies
      with propagation in the spatial frequency domain in order to constrain a fitting
      algorithm [Gaussian process (GP) regression] for estimating the axial intensity
      derivative. Solving the problem in the frequency domain inspires an efficient
      measurement scheme which captures images at exponentially spaced focal steps,
      significantly reducing the number of images required. Low-frequency artifacts
      that plague traditional TIE methods can be suppressed without an excessive number
      of captured images. We validate our technique experimentally by recovering the
      phase of human cheek cells in a brightfield microscope. 

PMID- 24921768
TI  - A corrugated perfect magnetic conductor surface supporting spoof surface magnon
      polaritons.
AB  - In this paper, we demonstrate that spoof surface magnon polaritons (SSMPs) can
      propagate along a corrugated perfect magnetic conductor (PMC) surface. From
      duality theorem, the existence of surface electromagnetic modes on corrugated PMC
      surfaces are manifest to be transverse electric (TE) mode compared with the
      transverse magnetic (TM) mode of spoof surface plasmon plaritons (SSPPs) excited
      on corrugated perfect electric conductor surfaces. Theoretical deduction through
      modal expansion method and simulation results clearly verify that SSMPs share the
      same dispersion relationship with the SSPPs. It is worth noting that this
      metamaterial will have more similar properties and potential applications as the
      SSPPs in large number of areas. 

PMID- 24921769
TI  - Modelization and optimized speckle detection scheme in photorefractive self
      referenced acousto-optic imaging.
AB  - A photorefractive BSO single crystal can be used for axially resolved acousto
      optic imaging of thick scattering media in absence of a reference beam. This
      configuration renders the experimental setup easier to realize for imaging
      through thick scattering media with an improved optical etendue. We present here
      a model and simulations that explains these results. It is based on the spatial
      heterogeneity of the speckle pattern incident on the crystal. Optimization of the
      detector position and of the speckle grain size is confirmed by the model. 

PMID- 24921770
TI  - Magnetic dipole radiation tailored by substrates: numerical investigation.
AB  - Nanoparticles of high refractive index materials can possess strong magnetic
      polarizabilities and give rise to artificial magnetism in the optical spectral
      range. While the response of individual dielectric or metal spherical particles
      can be described analytically via multipole decomposition in the Mie series, the
      influence of substrates, in many cases present in experimental observations,
      requires different approaches. Here, the comprehensive numerical studies of the
      influence of a substrate on the spectral response of high-index dielectric
      nanoparticles were performed. In particular, glass, perfect electric conductor,
      gold, and hyperbolic metamaterial substrates were investigated. Optical
      properties of nanoparticles were characterized via scattering cross-section
      spectra, electric field profiles, and induced electric and magnetic moments. The
      presence of substrates was shown to have significant impact on particle's
      magnetic resonances and resonant scattering cross-sections. Variation of
      substrate material provides an additional degree of freedom in tailoring optical
      properties of magnetic multipoles, important in many applications. 

PMID- 24921771
TI  - Low-loss high-speed silicon IQ modulator for QPSK/DQPSK in C and L bands.
AB  - A low-loss high-speed silicon in-phase (I) quadrature (Q) modulator is designed,
      fabricated and characterized. The fabricated IQ modulator has a low passive
      optical loss of 9 dB in C and L bands. Using the modulator, differential
      quadrature phase-shift keying (DQPSK) transmission at 44.6 Gb/s with differential
      detection is confirmed with an optical signal-to-noise ratio (OSNR) of 16.3 dB
      for a bit error rate (BER) of 10(-3) and a dispersion tolerance of -96 to 107
      ps/nm. Moreover, in digital coherent detection, quadrature phase-shift keying
      (QPSK) up to 64 Gb/s are achieved with an OSNR of 11.6-11.8 dB for a BER of 10(
      2) at 1530, 1550, and 1610 nm.

PMID- 24921772
TI  - Monolithic silicon waveguide photodiode utilizing surface-state absorption and
      operating at 10 Gb/s.
AB  - We have fabricated a waveguide integrated monolithic silicon infrared detector.
      The photodiode consists of a p-i-n junction across a silicon-on-insulator (SOI)
      rib waveguide. Absorption is due to surface-states at the silicon/air interface
      of the waveguide. A 2 mm long detector shows a response of 0.045 A/W (calculated
      as a function of coupled light) and is capable of operation at 10 Gb/s at a
      reverse bias voltage of 2 V.

PMID- 24921773
TI  - Monolithic multi-functional integration of ROADM modules based on polymer
      photonic lightwave circuit.
AB  - A transparent reconfigurable optical add-drop multiplexer (ROADM) module composed
      of AWG-based wavelength-channel-selectors monolithically integrated with Mach
      Zehnder interferometer (MZI) thermo-optic (TO) waveguide switch arrays and
      arrayed waveguide true-time-delay (TTD) lines is designed and fabricated using
      polymer photonic lightwave circuit technology. Negative-type fluorinated
      photoresist and grafting modified organic-inorganic hybrid materials were
      synthesized as the waveguide core and cladding, respectively. The one-chip
      transmission loss is ~6 dB and the crosstalk is less than ~30 dB for the
      transverse-magnetic (TM) mode. The actual maximum modulation depths of different
      thermo-optic switches are similar, ~15.5 dB with 1.9 V bias. The maximum power
      consumption of a single switch is less than 10 mW. The delay time basic
      increments are measured from 140 ps to 20 ps. Proposed novel ROADM is flexible
      and scalable for the dense wavelength division multiplexing network. 

PMID- 24921774
TI  - TIRF microscopy with ultra-short penetration depth.
AB  - Total internal reflection fluorescence microscopy (TIRF), in both commercial and
      custom-built configurations, is widely used for high signal-noise ratio imaging.
      The imaging depth of traditional TIRF is sensitive to the incident angle of the
      laser, and normally limited to around 100 nm. In our paper, using a high
      refractive index material and the evanescent waves of various waveguide modes, we
      propose a compact and tunable ultra-short decay length TIRF system, which can
      reach decay lengths as short as 19 nm, and demonstrate its application for
      imaging fluorescent dye-labeled F-actin in HeLa cells. 

PMID- 24921775
TI  - Multi-meter fiber-delivery and pulse self-compression of milli-Joule femtosecond
      laser and fiber-aided laser-micromachining.
AB  - We report on damage-free fiber-guidance of milli-Joule energy-level and 600
      femtosecond laser pulses into hypocycloid core-contour Kagome hollow-core
      photonic crystal fibers. Up to 10 meter-long fibers were used to successfully
      deliver Yb-laser pulses in robustly single-mode fashion. Different pulse
      propagation regimes were demonstrated by simply changing the fiber dispersion and
      gas. Self-compression to ~50 fs, and intensity-level nearing petawatt/cm(2) were
      achieved. Finally, free focusing-optics laser-micromachining was also
      demonstrated on different materials.

PMID- 24921776
TI  - Monochromatization of femtosecond XUV light pulses with the use of reflection
      zone plates.
AB  - We report on a newly built laser-based tabletop setup which enables generation of
      femtosecond light pulses in the XUV range employing the process of high-order
      harmonic generation (HHG) in a gas medium. The spatial, spectral, and temporal
      characteristics of the XUV beam are presented. Monochromatization of XUV light
      with minimum temporal pulse distortion is the central issue of this work. Off
      center reflection zone plates are shown to be advantageous when selection of a
      desired harmonic is carried out with the use of a single optical element. A cross
      correlation technique was applied to characterize the performance of the zone
      plates in the time domain. By using laser pulses of 25 fs length to pump the HHG
      process, a pulse duration of 45 fs for monochromatized harmonics was achieved in
      the present setup. 

PMID- 24921777
TI  - Edge effect modeling and experiments on active lap processing.
AB  - Edge effect is regarded as one of the most difficult technical issues for
      fabricating large primary mirrors, especially for large polishing tools. Computer
      controlled active lap (CCAL) uses a large size pad (e.g., 1/3 to 1/5 workpiece
      diameters) to grind and polish the primary mirror. Edge effect also exists in the
      CCAL process in our previous fabrication. In this paper the material removal
      rules when edge effects happen (i.e. edge tool influence functions (TIFs)) are
      obtained through experiments, which are carried out on a Phi1090-mm circular flat
      mirror with a 375-mm-diameter lap. Two methods are proposed to model the edge
      TIFs for CCAL. One is adopting the pressure distribution which is calculated
      based on the finite element analysis method. The other is building up a
      parametric equivalent pressure model to fit the removed material curve directly.
      Experimental results show that these two methods both effectively model the edge
      TIF of CCAL. 

PMID- 24921778
TI  - Continuous phase estimation from noisy fringe patterns based on the implicit
      smoothing splines.
AB  - We introduce the algorithm for the direct phase estimation from the single noisy
      interferometric pattern. The method, named implicit smoothing spline (ISS), can
      be regarded as a formal generalization of the smoothing spline interpolation for
      the case when the interpolated data is given implicitly. We derive the necessary
      equations, discuss the properties of the method and address its application for
      the direct estimation of the continuous phase in both classical interferometry
      and digital speckle pattern interferometry (DSPI). The numerical illustrations of
      the algorithm performance are provided to corroborate the high quality of the
      results. 

PMID- 24921779
TI  - Thermally driven dual-frequency Q-switching of Nd:YGd2Sc2Al2GaO12 ceramic laser.
AB  - Multi-wavelength operation of Q-switched Nd-doped YGd(2)Sc(2)Al(2)GaO(12) garnet
      ceramic lasers has been investigated. Dual-wavelength emission around ~1.06 um
      has been demonstrated both in the actively and passively Q-switched
      configurations. The ratio of output energy between the two laser wavelengths was
      driven by the temperature elevation caused by pumping. Passively Q-switched
      operation yields dual-frequency emission of two unsynchronized laser pulses
      carried by distinct transverse modes whereas active Q-switched configuration
      offers the possibility of synchronizing emission at the two wavelengths.

PMID- 24921780
TI  - Determining optimum operating conditions of the polarization-maintaining fiber
      with two far-lying zero dispersion wavelengths for CARS microscopy.
AB  - Single femtosecond laser-based coherent anti-Stokes Raman scattering (CARS)
      microscopy, using a photonic crystal fiber (PCF) pumped in the near-IR to
      generate a supercontinuum for the Stokes source, is rapidly being adopted as a
      cost-effective approach. A PCF with two closely-lying zero dispersion wavelengths
      is a popular choice for the Stokes source, but it is often limited to imaging
      lipids. A polarization-maintaining PCF with two far-lying zero dispersion
      wavelengths offers important advantages for polarization CARS microscopy, and for
      CARS imaging in the fingerprint region. This PCF fiber, though commercially
      available, has limited use for CARS microscopy in the C-H bond region. The main
      problem is that the supercontinuum from this fiber is typically noisier than that
      from a standard PCF with two closely-lying zero dispersion wavelengths. To
      overcome this, we determined the optimum operating conditions for generating a
      low-noise supercontinuum out of a PCF with two far-lying zero dispersion
      wavelengths, in terms of the input parameters of the excitation pulse. We
      measured the relative intensity noise (RIN) of the Stokes and the corresponding
      CARS signal as a function of the input laser parameters in this fiber. We showed
      that the results of CARS imaging using this alternate fiber are comparable to
      those achieved using the standard fiber, for input laser pulse conditions of low
      average power, narrow pulse width with slightly positive chirp, and polarization
      direction parallel to the slow axis of the selected fiber. 

PMID- 24921781
TI  - A non-orthogonal coupled mode theory for super-modes inside multi-core fibers.
AB  - In this paper, a non-orthogonal coupled mode theory is proposed to analyze the
      super-modes of multi-core fibers (MCFs). The theory is valid in the strong
      coupling regime and can provide accurate analytical formulas for the super-modes
      inside MCFs. MCFs with circularly distributed cores are analyzed as an example.
      Analytical formulas are derived both for the refractive indexes and the eigen
      vectors of the super-modes. It is rigorously revealed that the eigen vectors for
      the super-modes of such MCFs are the row vectors of the inverse discrete Fourier
      transform (IDFT) matrix. Therefore, by pre-coding the signal channels via IDFT,
      one is able to generate the super-modes for the MCFs with circularly distributed
      cores. 

PMID- 24921782
TI  - Optical detection and modulation at 2um-2.5um in silicon.
AB  - Recently the 2MUm wavelength region has emerged as an exciting prospect for the
      next generation of telecommunications. In this paper we experimentally
      characterise silicon based plasma dispersion effect optical modulation and defect
      based photodetection in the 2-2.5MUm wavelength range. It is shown that the
      effectiveness of the plasma dispersion effect is dramatically increased in this
      wavelength window as compared to the traditional telecommunications wavelengths
      of 1.3MUm and 1.55MUm. Experimental results from the defect based photodetectors
      show that detection is achieved in the 2-2.5MUm wavelength range, however the
      responsivity is reduced as the wavelength is increased away from 1.55MUm. 

PMID- 24921783
TI  - Time domain adjoint sensitivity analysis of electromagnetic problems with
      nonlinear media.
AB  - In this paper, we propose a theory for wideband adjoint sensitivity analysis of
      problems with nonlinear media. We show that the sensitivities of the desired
      response with respect to all shape and material parameters are obtained through
      one extra adjoint simulation. Unlike linear problems, the system matrices of this
      adjoint simulation are time varying. Their values are determined during the
      original simulation. The proposed theory exploits the time-domain transmission
      line modeling (TLM) and provides an efficient AVM approach for sensitivity
      analysis of general time domain objective functions. The theory has been
      illustrated through a number of examples. 

PMID- 24921784
TI  - Digital quadrature amplitude modulation with optimized non-rectangular
      constellations for 100 Gb/s transmission by a directly-modulated laser.
AB  - We study the performance of novel quadrature amplitude modulation (QAM)
      constellations for 100 Gb/s transmission by a directly-modulated laser. Due to
      the strong nonlinearity of a directly-modulated laser, rectangular constellations
      suffer a large penalty from their regular spacing between symbols. We present a
      method for synthesizing irregular constellations which position symbols more
      efficiently. We will demonstrate the improved performance of these novel
      constellations over the conventional rectangular constellation as well as the
      superior performance achievable with digital QAM compared to optimally bit-loaded
      discrete-multitone modulation. 

PMID- 24921785
TI  - Wavelength-dependent longitudinal polarizability of gold nanorod on optical
      torques.
AB  - This study theoretically investigates the wavelength-dependent longitudinal
      polarizability of a gold nanorod (GNR) irradiated by a polarized laser beam. The
      resultant optical torque in terms of the Maxwell stress tensor was analyzed
      quantitatively using the multiple multipole method. Our results indicate that the
      real part of the longitudinal polarizability of GNR can be either positive or
      negative, leading to the parallel or perpendicular modes, respectively. For the
      parallel and perpendicular modes, the long axis of GNR is rotated to align
      parallel and perpendicular, respectively, to the polarization direction of the
      illuminating light. The turning point between these two modes, depending on the
      aspect ratio (AR) and the size of GNR, nearly coincides with the longitudinal
      surface plasmon resonance (LSPR). The perpendicular mode ranges from the
      transverse SPR to LSPR, and the range of the parallel mode is broadband from LSPR
      to the near infrared regime. Owing to that a larger optical torque and less
      plasmonic heating are of concern, an efficiency of optical torque is defined to
      evaluate the performance of different wavelengths. Analysis results indicate that
      lasers with wavelength in the perpendicular mode are applicable to rotate and
      align a GNR of a higher AR. For example, the laser of 785 nm (the perpendicular
      mode) is superior to that of 1064 nm (the parallel mode, off-resonant from LSPR
      of 955 nm) for rotating a GNR of AR = 4 and radius 20 nm with an orientation of
      45 degrees  with respect to the laser polarization. 

PMID- 24921786
TI  - All-optical reservoir computer based on saturation of absorption.
AB  - Reservoir computing is a new bio-inspired computation paradigm. It exploits a
      dynamical system driven by a time-dependent input to carry out computation. For
      efficient information processing, only a few parameters of the reservoir needs to
      be tuned, which makes it a promising framework for hardware implementation.
      Recently, electronic, opto-electronic and all-optical experimental reservoir
      computers were reported. In those implementations, the nonlinear response of the
      reservoir is provided by active devices such as optoelectronic modulators or
      optical amplifiers. By contrast, we propose here the first reservoir computer
      based on a fully passive nonlinearity, namely the saturable absorption of a
      semiconductor mirror. Our experimental setup constitutes an important step
      towards the development of ultrafast low-consumption analog computers. 

PMID- 24921787
TI  - Design of DPSS based fiber bragg gratings and their application in all-optical
      encryption, OCDMA, optical steganography, and orthogonal-division multiplexing.
AB  - The future information infrastructure will be affected by limited bandwidth of
      optical networks, high energy consumption, heterogeneity of network segments, and
      security issues. As a solution to all problems, we advocate the use of both
      electrical basis functions (orthogonal prolate spheroidal basis functions) and
      optical basis functions, implemented as FBGs with orthogonal impulse response in
      addition to spatial modes. We design the Bragg gratings with orthogonal impulse
      responses by means of discrete layer peeling algorithm. The target impulse
      responses belong to the class of discrete prolate spheroidal sequences, which are
      mutually orthogonal regardless of the sequence order, while occupying the fixed
      bandwidth. We then design the corresponding encoders and decoders suitable for
      all-optical encryption, optical CDMA, optical steganography, and orthogonal
      division multiplexing (ODM). Finally, we propose the spectral multiplexing-ODM
      spatial multiplexing scheme enabling beyond 10 Pb/s serial optical transport
      networks. 

PMID- 24921788
TI  - Remote state preparation of three-dimensional optical vortices.
AB  - We propose a feasible scheme to remotely prepare three-dimensional (3D) optical
      vortex lines. Our scheme relies on the complete description of high-dimensional
      orbital angular momentum (OAM) entanglement in terms of the Laguerre-Gaussian
      modes. It is theoretically demonstrated that by simply changing the pump beam
      waist, we can remotely prepare the target photons in the vortex states of 3D
      interesting morphology, appearing as twisted vortex strands, separated vortex
      loops, and vortex link or knot. Furthermore, we employ the biphoton Klyshko
      picture to illustrate the conservation law of the OAM index l and the spreading
      effect of the radial mode index p, where the Schmidt numbers are calculated to
      show the high-dimensional capacity of the quantum channels involved in the
      present remote state preparation. 

PMID- 24921789
TI  - Dual-wavelength rectangular pulse Yb-doped fiber laser using a microfiber-based
      graphene saturable absorber.
AB  - We reported on the generation of dual-wavelength rectangular pulses in a Yb-doped
      fiber laser (YDFL) by using a microfiber-based graphene saturable absorber (GSA).
      The duration of dual-wavelength rectangular pulse could be varied from 1.41 ns to
      4.23 ns with the increasing pump power. With a tunable bandpass filter, it was
      found that the characteristics of the rectangular pulses centered at 1061.8 nm
      and 1068.8 nm are similar to each other. Moreover, the dual-wavelength switchable
      operation was also realized by properly rotating the polarization controllers
      (PCs). The demonstration of the dual-wavelength rectangular pulses from a YDFL
      would open some applications for fields such as spectroscopy, biomedicine and
      sensing research. 

PMID- 24921790
TI  - High-resolution low-noise 360-degree digital solid reconstruction using phase
      stepping profilometry.
AB  - In this paper we describe a high-resolution, low-noise phase-shifting algorithm
      applied to 360 degree digitizing of solids with diffuse light scattering surface.
      A 360 degree profilometer needs to rotate the object a full revolution to
      digitize a three-dimensional (3D) solid. Although 360 degree profilometry is not
      new, we are proposing however a new experimental set-up which permits full phase
      bandwidth phase-measuring algorithms. The first advantage of our solid
      profilometer is: it uses base-band, phase-stepping algorithms providing full data
      phase-bandwidth. This contrasts with band-pass, spatial-carrier Fourier
      profilometry which typically uses 1/3 of the fringe data-bandwidth. In addition
      phase-measuring is generally more accurate than single line-projection, non
      coherent, intensity-based line detection algorithms. Second advantage: new fringe
      projection set-up which avoids self-occluding fringe-shadows for convex solids.
      Previous 360 degree fringe-projection profilometers generate self-occluding
      shadows because of the elevation illumination angles. Third advantage: trivial
      line-by-line fringe-data assembling based on a single cylindrical coordinate
      system shared by all 360-degree perspectives. This contrasts with multi-view
      overlapping fringe-projection systems which use iterative closest point (ICP)
      algorithms to fusion the 3D-data cloud within a single coordinate system (e.g.
      Geomagic). Finally we used a 400 steps/rotation turntable, and a 640x480 pixels
      CCD camera. Higher 3D digitized surface resolutions and less-noisy phase
      measurements are trivial by increasing the angular-spatial resolution and phase
      steps number without any substantial change on our 360 degree profilometer. 

PMID- 24921791
TI  - Full flex-grid asynchronous multiplexing demonstrated with Nyquist pulse-shaping.
AB  - We demonstrate full flex-grid operation with Nyquist frequency division
      multiplexing. The technique supports high spectral efficiency, asynchronous
      operation of channels, variable channel loading with different modulation formats
      and dynamic bandwidth allocation. Data from different sources with different bit
      and symbol rates are encoded onto electrical Nyquist pulses with different
      electrical subcarrier frequencies, and then transmitted optically. We give
      details on the transceiver design with digital signal processing and investigate
      the implementation penalty as a function of several design parameters such as
      limited filter length and effective number of bits. Finally, experiments are
      performed for receivers with direct detection, intradyne and remote heterodyne
      reception. 

PMID- 24921792
TI  - Wide bandwidth and high coupling efficiency Si3N4-on-SOI dual-level grating
      coupler.
AB  - We propose and experimentally demonstrate fiber-to-chip grating couplers with
      aligned silicon nitride (Si(3)N(4)) and silicon (Si) grating teeth for wide
      bandwidths and high coupling efficiencies without the use of bottom reflectors.
      The measured 1-dB bandwidth is a record 80 nm, and the measured peak coupling
      efficiency is -1.3 dB, which is competitive with the best Si-only grating
      couplers. The grating couplers are integrated in a Si(3)N(4) on silicon-on
      insulator (SOI) integrated optics platform with aligned waveguides in both the
      Si(3)N(4) and Si, and we demonstrate a 1 * 4 tunable multiplexer/demultiplexer
      using the Si(3)N(4)-on-SOI dual-level grating couplers and thermally-tuned Si
      microring resonators.

PMID- 24921793
TI  - First on-sky results of the CO-SLIDAR C(2)(n) profiler.
AB  - COupled SLope and scIntillation Detection And Ranging (CO-SLIDAR) is a recent
      profiling method of the vertical distribution of atmospheric turbulence strength
      (C(2)(n) profile). It takes advantage of correlations of slopes and of
      scintillation, both measured with a Shack-Hartmann wavefront sensor on a binary
      star. In this paper, we present the improved CO-SLIDAR reconstruction method of
      the C(2)(n) profile and the first on-sky results of the CO-SLIDAR profiler. We
      examine CO-SLIDAR latest performance in simulation, taking into account the
      detection noise bias and estimating error bars along with the turbulence profile.
      The estimated C(2)(n) profiles demonstrate the accuracy of the CO-SLIDAR method,
      showing sensitivity to both low and high altitude turbulent layers. CO-SLIDAR is
      tested on-sky for the first time, on the 1.5 m MeO (Metrologie Optique) telescope
      at Observatoire de la Cote d'Azur (France). The reconstructed profiles are
      compared to turbulence profiles estimated from meteorological data and a good
      agreement is found. We discuss CO-SLIDAR's contribution in the C(2)(n) profilers'
      landscape and we propose some improvements of the instrument.

PMID- 24921794
TI  - Dissociative recombination in ultraviolet filamentary plasma gratings.
AB  - We investigated collisions of nitrogen and argon gas mixture with energetic
      electrons accelerated by Bragg incident intense infrared femtosecond laser pulses
      in ultraviolet filamentary plasma gratings. Significant decrease of fluorescence
      spectra of argon atoms were observed when a small amount of nitrogen gas was
      mixed with argon gas that facilitated observable argon-nitrogen collisions. We
      experimentally measured the fluorescence emission from the argon and nitrogen gas
      mixture under different driving pulse energies, the fluorescence decay dynamics
      after the impact excitation, as well as the fluorescence intensity dependence on
      the nitrogen and argon pressures. The experimental measurements were based on the
      electron acceleration and its subsequent impact with the gas mixture in the
      filamentary plasma gratings, which was essential for the observation of the
      dominant dissociative recombination in the gas mixture. 

PMID- 24921795
TI  - Dual-polarization multi-band optical OFDM transmission and transceiver
      limitations for up to 500 Gb/s uncompensated long-haul links.
AB  - A number of critical issues for dual-polarization single- and multi-band optical
      orthogonal-frequency division multiplexing (DP-SB/MB-OFDM) signals are analyzed
      in dispersion compensation fiber (DCF)-free long-haul links. For the first time,
      different DP crosstalk removal techniques are compared, the maximum transmission
      reach is investigated, and the impact of subcarrier number and high-level
      modulation formats are explored thoroughly. It is shown, for a bit-error-rate
      (BER) of 10(-3), 2000 km of quaternary phase-shift keying (QPSK) DP-MB-OFDM
      transmission is feasible. At high launched optical powers (LOP), maximum
      likelihood decoding can extend the LOP of 40 Gb/s QPSK DP-SB-OFDM at 2000 km by
      1.5 dB compared to zero-forcing. For a 100 Gb/s DP-MB-OFDM system, a high number
      of subcarriers contribute to improved BER but at the cost of digital signal
      processing computational complexity, whilst by adapting the cyclic prefix length
      the BER can be improved for a low number of subcarriers. In addition, when 16
      quadrature amplitude modulation (16QAM) is employed the digital-to
      analogue/analogue-to-digital converter (DAC/ADC) bandwidth is relaxed with a
      degraded BER; while the 'circular' 8QAM is slightly superior to its 'rectangular'
      form. Finally, the transmission of wavelength-division multiplexing DP-MB-OFDM
      and single-carrier DP-QPSK is experimentally compared for up to 500 Gb/s showing
      great potential and similar performance at 1000 km DCF-free G.652 line.

PMID- 24921796
TI  - Ultrafast all-optical modulation with hyperbolic metamaterial integrated in Si
      photonic circuitry.
AB  - The integration of optical metamaterials within silicon integrated photonic
      circuitry bears significantly potential in the design of low-power, nanoscale
      footprint, all-optical functionalities. We propose a novel concept and provide
      detailed analysis of an on-chip ultrafast all-optical modulator based on an
      hyperbolic metamaterial integrated in a silicon waveguide. The anisotropic
      metamaterial based on gold nanorods is placed on top of the silicon waveguide to
      form a modulator with a 300x440x600 nm(3) footprint. For the operating wavelength
      of 1.5 MUm, the optimized geometry of the device has insertion loss of about 5 dB
      and a modulation depth of 35% with a sub-ps switching rate. The switching energy
      estimated from nonlinear transient dynamic numerical simulations is 3.7 pJ/bit
      when the transmission is controlled optically at a wavelength of 532 nm, resonant
      with the transverse plasmonic mode of the metamaterial. The switching mechanism
      is based on the control of the hybridization of eigenmodes in the metamaterial
      slab and the Si waveguide.

PMID- 24921797
TI  - Tuning resonant interaction of orthogonally polarized solitons and dispersive
      waves with the soliton power.
AB  - We demonstrate that the relatively small power induced changes in the soliton
      wavenumber comparable with splitting of the effective indexes of the orthogonally
      polarized waveguide modes result in significant changes of the efficiency of the
      interaction between solitons and dispersive waves and can be used to control
      energy transfer between the soliton and newly generated waves and to delay or
      accelerate solitons. 

PMID- 24921798
TI  - Axial standing-wave illumination frequency-domain imaging (SWIF).
AB  - Despite their tremendous contribution to biomedical research and diagnosis,
      conventional spatial sampling techniques such as wide-field, point scanning or
      selective plane illumination microscopy face inherent limiting trade-offs between
      spatial resolution, field-of-view, phototoxicity and recording speed. Several of
      these trade-offs are the result of spatial sampling with diffracting beams. Here,
      we introduce a new strategy for fluorescence imaging, SWIF, which instead encodes
      the axial profile of a sample in the Fourier domain. We demonstrate how this can
      be achieved with propagation-invariant illumination patterns that extend over
      several millimeters and robustly propagate through layers of varying refractive
      index. This enabled us to image a lateral field-of-view of 0.8 mm x 1.5 mm with
      an axial resolution of 2.4 um - greatly exceeding the lateral field-of-view of
      conventional illumination techniques (~100 um) at comparable resolution. Thus,
      SWIF allowed us to surpass the limitations of diffracting illumination beams and
      untangle lateral field-of-view from resolution. 

PMID- 24921799
TI  - Dielectric multilayer beam splitter with differential phase shift on transmission
      and reflection for division-of-amplitude photopolarimeter.
AB  - Dielectric multilayer beam splitter with differential phase shift on transmission
      and reflection for division-of-amplitude photopolarimeter (DOAP) was presented
      for the first time to our knowledge. The optimal parameters for the beam splitter
      are Tp = 78.9%, Ts = 21.1% and Deltar - Deltat = pi/2 at 532nm at an angle of
      incidence of 45 degrees . Multilayer anti-reflection coating with low phase shift
      was applied to reduce the backside reflection. Different design strategies that
      can achieve all optimal targets at the wavelength were tested. Two design methods
      were presented to optimize the differential phase shift. The samples were
      prepared by ion beam sputtering (IBS). The experimental results show good
      agreement with those of the design. The ellipsometric parameters of samples were
      measured in reflection (psir, Deltar) = (26.5 degrees , 135.1 degrees ) and (28.2
      degrees , 133.5 degrees ), as well as in transmission (psit, Deltat) = (62.5
      degrees , 46.1 degrees ) and (63.5 degrees , 46 degrees ) at 532.6nm. The
      normalized determinant of instrument matrix to evaluate the performance of
      samples is respectively 0.998 and 0.991 at 532.6nm.

PMID- 24921800
TI  - High efficiency asymmetric directional coupler for slow light slot photonic
      crystal waveguides.
AB  - An asymmetric directional coupler scheme for the efficient injection of light
      into slow light slot photonic crystal waveguide modes is proposed and
      investigated using finite-difference time-domain simulation. Coupling wavelengths
      can be flexibly controlled by the geometrical parameters of a side-coupled
      subwavelength corrugated strip waveguide. This approach leads to a ~1dB insertion
      loss level up to moderately high light group indices (nG~30) in wavelength ranges
      of 5-10nm. This work brings new opportunities to inject light into the slow modes
      of slot photonic crystal waveguides for on-chip communications using hybrid
      silicon photonics or sensing based on hollow core waveguides.

PMID- 24921801
TI  - Infrared photoresponse of GeSn/n-Ge heterojunctions grown by molecular beam
      epitaxy.
AB  - Heterojunction devices of Ge(1-x)Sn(x) / n-Ge were grown by solid source
      molecular beam epitaxy (MBE), and the mid-infrared (IR) photocurrent response was
      measured. With increasing Sn composition from 4% to 12%, the photocurrent spectra
      became red-shifted, suggesting that the bandgap of Ge(1-x)Sn(x) alloys was
      lowered compared to pure Ge. At a temperature of 100 K, the wavelengths of peak
      photocurrent were shifted from 1.42 um for pure Ge (0% Sn) to 2.0 um for 12% Sn.
      The bias dependence of the device response showed that the optimum reverse bias
      was > 0.5 volts for saturated photocurrent. The responsivity of the Ge(1-x)Sn(x)
      devices was estimated to be 0.17 A/W for 4% Sn. These results suggest that Ge(1
      x)Sn(x) photodetectors may have practical applications in the near/mid IR
      wavelength regime.

PMID- 24921802
TI  - Fabrication of micro-axicons using direct-laser writing.
AB  - A novel direct-laser writing fabrication process for micro-axicons is
      demonstrated. A fiber-axicon-generated Bessel beam was utilized to write on UV
      curable optical epoxy to form new axicons and axicon arrays, and geometrical
      parameters of the replicated epoxy axicons were analyzed in terms of both apex
      angle and proximity of the writing axicons. The shape of the fabricated axicons
      was demonstrated to be controllable through laser exposure, proximity, and apex
      angle of the source axicon, and the fabricated axicons are capable of generating
      a quality Bessel beam with an excellent focusing performance. 

PMID- 24921803
TI  - Direct observation of light focusing by single photoreceptor cell nuclei.
AB  - The vertebrate retina is inverted with respect to its optical function, which
      requires light to pass through the entire tissue prior to detection. The last
      significant barrier for photons to overcome is the outer nuclear layer formed by
      photoreceptor cell (PRC) nuclei. Here we experimentally characterise the optical
      properties of PRC nuclei using bright-field defocusing microscopy to capture near
      field intensity distributions behind individual nuclei. We find that some nuclei
      efficiently focus incident light confirming earlier predictions based on
      comparative studies of chromatin organisation in nocturnal and diurnal mammals.
      The emergence of light focusing during the development of mouse nuclei highlights
      the acquired nature of the observed lens-like behaviour. Optical characterisation
      of these nuclei is an important first step towards an improved understanding of
      how light transmission through the retina is influenced by its constituents. 

PMID- 24921804
TI  - Terahertz phase contrast imaging of sorption kinetics in porous coordination
      polymer nanocrystals using differential optical resonator.
AB  - The enhancement of light-matter coupling when light is confined to wavelength
      scale volumes is useful both for studying small sample volumes and increasing the
      overall sensing ability. At these length scales, nonradiative interactions are of
      key interest to which near-field optical techniques may reveal new phenomena
      facilitating next-generation material functionalities and applications. Efforts
      to develop novel chemical or biological sensors using metamaterials have yielded
      innovative ideas in the optical and terahertz frequency range whereby the
      spatially integrated response over a resonator structure is monitored via the re
      radiated or leaked light. But although terahertz waves generally exhibit
      distinctive response in chemical molecules or biological tissue, there is little
      absorption for subwavelength size sample and therefore poor image contrast. Here,
      we introduce a method that spatially resolves the differential near-field phase
      response of the entire resonator as a spectral fingerprint. By simultaneously
      probing two metallic ring resonators, where one loaded with the sample of
      interest, the differential phase response is able to resolve the presence of
      guest molecules (e.g. methanol) as they are adsorbed or released within the pores
      of a prototypical porous coordination polymer. 

PMID- 24921805
TI  - Photoinduced active terahertz metamaterials with nanostructured vanadium dioxide
      film deposited by sol-gel method.
AB  - Applying the photoexcitation characteristics of vanadium dioxide (VO(2)), a
      dynamic resonant terahertz (THz) functional device with the combination of VO(2)
      film and dual-resonance metamaterial was suggested to realize the ultrafast
      external spatial THz wave active manipulation. The designed metamaterial realizes
      a pass band at 0.28-0.36 THz between the dual-resonant frequencies, and the VO(2)
      film is applied to control the transmittance of the spatial THz wave. More than
      an 80% modulation depth has been observed in the statics experiment, and the
      dynamic experimental results illustrate that this active metamaterial realizes up
      to a 1 MHz amplitude modulation signal loaded on a 0.34 THz carrier wave without
      any low noise amplified devices. The electromagnetic properties and photoinduced
      dynamic characteristics of this structure may have many potential applications in
      THz functional components, including modulators, intelligent switches, and
      sensors.

PMID- 24921806
TI  - Vortex algebra by multiply cascaded four-wave mixing of femtosecond optical
      beams.
AB  - Experiments performed with different vortex pump beams show for the first time
      the algebra of the vortex topological charge cascade, that evolves in the process
      of nonlinear wave mixing of optical vortex beams in Kerr media due to competition
      of four-wave mixing with self-and cross-phase modulation. This leads to the
      coherent generation of complex singular beams within a spectral bandwidth larger
      than 200nm. Our experimental results are in good agreement with frequency-domain
      numerical calculations that describe the newly generated spectral satellites. 

PMID- 24921807
TI  - Graphene oxide-based waveguide polariser: from thin film to quasi-bulk.
AB  - We have demonstrated a broadband waveguide polariser with high extinction ratio
      on a polymer optical waveguide coated with graphene oxide via the drop-casting
      method. The highest extinction ratio of nearly 40 dB is measured at 1590 nm, with
      a variation of 4.5 dB across a wavelength range from 1530 nm to 1630 nm, a ratio
      that is (to our knowledge) the highest reported for graphene-based waveguide
      polarisers to date. This result is achieved with a graphene oxide coating length
      along the propagation direction of only 1.3 mm and a bulk film thickness of 2.0
      um. The underlying principles of the strongly polarisation dependent propagation
      loss demonstrated have been studied and are attributed to the anisotropic complex
      dielectric function of graphene oxide bulk film. 

PMID- 24921808
TI  - Characterization of the spatiotemporal evolution of ultrashort optical pulses
      using FROG holography.
AB  - We propose holographically recorded frequency-resolved-optical-gating (FROG)
      measurement for probing the evolution of ultrashort optical pulses at multiple
      locations. As a proof-of-concept demonstration of our method, we record
      holographic FROG traces at five axial locations as we traverse through the focus
      of an objective lens along its axis using BaTiO(3) micro-cluster as the nonlinear
      medium and retrieve the amplitude and phase of the ultrashort pulse at each
      location. Moreover, the group delay of the pulse retrieved numerically using FROG
      holography is used to compute the separation between the five locations which
      agree well with the experimentally measured distances. This study suggests that
      FROG holography can be used to remove the ambiguity regarding arbitrary constant
      phase and arbitrary temporal shift in the retrieved pulse at each location (upto
      to an overall constant phase).

PMID- 24921809
TI  - Design of dual-link (wide- and narrow-beam) LED communication systems.
AB  - We explore the design of an LED-based communication system comprising two free
      space optical links: one narrow-beam (primary) link for bulk data transmission
      and one wide-beam (beacon) link for alignment and support of the narrow-beam
      link. Such a system combines the high throughput of a highly directional link
      with the robust insensitivity to pointing errors of a wider-beam link. We develop
      a modeling framework for this dual-link configuration and then use this framework
      to explore system tradeoffs in power, range, and achievable rates. The proposed
      design presents a low-cost, compact, robust means of communication at short- to
      medium-ranges, and calculations show that data rates on the order of Mb/s are
      achievable at hundreds of meters with only a few LEDs. 

PMID- 24921810
TI  - 650-nm 1 * 2 polymeric thermo-optic switch with low power consumption.
AB  - In this paper, a low-power 1 * 2 polymeric thermo-optic switch operating at the
      polymer optical fiber low-loss window of 650 nm was studied. The characteristic
      parameters of the switch were carefully designed and simulated. The fabrication
      was done by using standard semiconductor fabrication techniques such as spin
      coating, photolithography, and dry etching. The device was fabricated based on
      poly(methyl methacrylate) (PMMA)-based materials with the Mach-Zehnder
      interferometer (MZI) structure. The device shows an extinction ratio of over 23.4
      dB at 650 nm with a very low-power consumption of 5.3 mW. The measured switching
      rise time and fall time are 464.4 and 448.0 us, respectively. 

PMID- 24921811
TI  - Optical length change measurement via RF frequency shift analysis of incoherent
      light source based optoelectronic oscillator.
AB  - Radio-frequency (RF) frequency shift of incoherent light source based
      optoelectronic oscillator (OEO) is employed to measure the optical length change.
      In the proposed OEO using an incoherent light source, the optical length under
      test is inserted in the optoelectronic hybrid loop. The frequency shift of RF
      oscillation modes at the output of the OEO reflects the optical length change,
      with the change being measured via frequency shift analysis. Two OEO
      configurations are theoretically designed and experimentally performed, while an
      amplified spontaneous emission (ASE) source serves as the incoherent light
      source. A linear relationship between the frequency shift and the optical length
      change has been confirmed for measurement, and a reconfigurable measurement
      sensitivity is available by selecting different oscillation modes. Moreover, the
      use of ASE greatly reduces the complexity and the cost for stabilization control
      on light source, while the derived results are consistent with that obtained in a
      laser source based OEO both in the measured optical length changes and the phase
      noise performance. A sensitivity of -28 KHz/cm, -480 KHz/cm or higher, and a
      resolution of nano-meter scale are obtained, which can be used to monitor the
      displacement, the changes in refractive index, temperature. 

PMID- 24921812
TI  - Vectorial point spread function and optical transfer function in oblique plane
      imaging.
AB  - Oblique plane imaging, using remote focusing with a tilted mirror, enables direct
      two-dimensional (2D) imaging of any inclined plane of interest in three
      dimensional (3D) specimens. It can image real-time dynamics of a living sample
      that changes rapidly or evolves its structure along arbitrary orientations. It
      also allows direct observations of any tilted target plane in an object of which
      orientational information is inaccessible during sample preparation. In this
      work, we study the optical resolution of this innovative wide-field imaging
      method. Using the vectorial diffraction theory, we formulate the vectorial point
      spread function (PSF) of direct oblique plane imaging. The anisotropic lateral
      resolving power caused by light clipping from the tilted mirror is theoretically
      analyzed for all oblique angles. We show that the 2D PSF in oblique plane imaging
      is conceptually different from the inclined 2D slice of the 3D PSF in
      conventional lateral imaging. Vectorial optical transfer function (OTF) of
      oblique plane imaging is also calculated by the fast Fourier transform (FFT)
      method to study effects of oblique angles on frequency responses. 

PMID- 24921813
TI  - Speckle reduction in laser projection using a dynamic deformable mirror.
AB  - Despite of much effort and significant progress in recent years, speckle removal
      is still a challenge for laser projection technology. In this paper, speckle
      reduction by dynamic deformable mirror was investigated. Time varying independent
      speckle patterns were generated due to the angle diversity introduced by the
      dynamic mirror, and these speckle patterns were averaged out by the camera or
      human eyes, thus reducing speckle contrast in the final image. The speckle
      reduction by the wavelength diversity of the lasers was also studied. Both
      broadband lasers and narrowband laser were used for experiment. It is
      experimentally shown that speckle suppression can be attained by the widening of
      the spectrum of the lasers. Lower speckle contrast reduction was attained by the
      wavelength diversity for narrowband laser compared to the broadband lasers. This
      method of speckle reduction is suitable in laser projectors for wide screen
      applications where high power laser illumination is needed. 

PMID- 24921815
TI  - Reflective composite sheet design for LCD backlight recycling.
AB  - We have designed a reflective composite sheet consisting of a birefringent
      polymer matrix and isolated isotropic or minimally birefringent fibers. The
      optical properties of the sheet have been investigated in terms of the width,
      spacing, and thickness of the individual fibers. Commercial software (FDTD
      Solution) was used to simulate the reflectance of the proposed sheet, and
      conventional processes such as cast-film extrusion in combination with solid
      state drawing were used to manufacture the multilayer composite sheet. The
      measured and simulated reflectance spectra confirm the feasibility of employing
      the sheet as a reflective polarizer. 

PMID- 24921814
TI  - Polarization rotator-splitters and controllers in a Si3N4-on-SOI integrated
      photonics platform.
AB  - We demonstrate novel polarization management devices in a custom-designed silicon
      nitride (Si(3)N(4)) on silicon-on-insulator (SOI) integrated photonics platform.
      In the platform, Si(3)N(4) waveguides are defined atop silicon waveguides. A
      broadband polarization rotator-splitter using a TM0-TE1 mode converter in a
      composite Si(3)N(4)-silicon waveguide is demonstrated. The polarization
      crosstalk, insertion loss, and polarization dependent loss are less than -19 dB,
      1.5 dB, and 1.0 dB, respectively, over a bandwidth of 80 nm. A polarization
      controller composed of polarization rotator-splitters, multimode interference
      couplers, and thin film heaters is also demonstrated.

PMID- 24921816
TI  - Tunable, continuous-wave optical parametric oscillator with more than 1W output
      power in the orange visible spectrum.
AB  - We report on the implementation of an all-solid-state optical parametric
      oscillator (OPO) laser system, pumped by a fiber laser, and extended by intra
      cavity sum frequency generation (SFG) to provide tunable radiation with output
      powers well beyond 1 W in the visible regime between 605 and 616 nm. We use
      periodically poled sections for quasi phase-matched OPO and SFG processes,
      implemented on a single MgO:PPLN crystal. A Pound-Drever-Hall frequency
      stabilization reduces the laser linewidth to the range of 100 kHz (FWHM),
      determined by measurements of spectral hole burning in a rare-earth ion doped
      crystal as well as analysis of side-of-fringe transmission in a low finesse Fabry
      Perot resonator. 

PMID- 24921817
TI  - Projection-based disparity control for toed-in multiview images.
AB  - The multiview images captured by toed-in camera array can reproduce the 3D scene
      vividly with appropriate positive, negative, and zero disparities. However, it is
      a challenging task to adjust the depth of the scene according to requirements of
      visual effects. In this paper, we propose a novel disparity control method based
      on projection to solve this problem. With the relationship between the world
      coordinate system and camera coordinate system, the zero disparity point in
      reference view is projected into other views. Thus, disparities of different
      views are obtained through matched corresponding points and views are shifted
      with calculated disparities. The proposed method is easy to implement, and the
      depth of toed-in multiview images can be adjusted as requirements. Experiment
      results show that the proposed method is effective in comparison to the
      conventional method, and the processed multiview images present desirable
      stereoscopic visual quality. 

PMID- 24921818
TI  - Frequency down-conversion of 637 nm light to the telecommunication band for non
      classical light emitted from NV centers in diamond.
AB  - We demonstrate a low-noise frequency down-conversion of photons at 637 nm to the
      telecommunication band at 1587 nm by the difference frequency generation in a
      periodically-poled lithium niobate. An internal conversion efficiency of the
      converter is estimated to be 0.44 at the maximum which is achieved by a pump
      power of 0.43 W, whereas a rate of internal background photons caused by the
      strong cw pump laser is estimated to be 9 kHz/mW within a bandwidth of about 1
      nm. By using the experimental values related to the intrinsic property of the
      converter, and using the intensity correlation and the average photon number of a
      637 nm input light pulse, we derive the intensity correlation of a converted
      telecom light pulse. Then we discuss feasibility of a single-photon frequency
      conversion to the telecommunication band for a long-distance quantum
      communication based on NV centers in diamond. 

PMID- 24921819
TI  - Three-dimensional structured illumination microscopy using Lukosz bound
      apodization reduces pixel negativity at no resolution cost.
AB  - The quality of the reconstructed image in structured illumination microscopy
      (SIM) depends on various aspects of the image filtering process. To optimize the
      trade-off between resolution and ringing artifacts, which lead to negative
      intensities, we extend Lukosz-bound filtering to 3D SIM and derive the
      parametrization of the 3D SIM cut-off. We compare the use of the Lukosz-bound as
      apodization filter to triangular apodization and find a tenfold reduction in the
      most negative pixel value with a minimal resolution loss. We test this algorithm
      on experimental SIM images of tubulin filaments and DAPI stained DNA structure in
      cancer cells and find a substantial reduction in the most negative pixel value
      and the percentage of pixels with a negative value. This means that there is no
      longer a need to clip the final image to avoid these negative pixel values. 

PMID- 24921820
TI  - Full characterization of the amplified spontaneous emission from a diode-pumped
      high-power laser system.
AB  - We present the first complete temporal and spatial characterization of the
      amplified spontaneous emission (ASE) of laser radiation generated by a diode
      pumped high-power laser system. The ASE of the different amplifiers was measured
      independently from the main pulse and was characterized within a time window of 
      10ms <= t <= 10ms and an accuracy of up to 15fs around the main pulse.
      Furthermore, the focusability and the energy of the ASE from each amplifier was
      measured after recompression. Using our analysis method, the laser components,
      which need to be optimized for a further improvement of the laser contrast, can
      be identified. This will be essential for laser-matter interaction experiments
      requiring a minimized ASE intensity or fluence. 

PMID- 24921821
TI  - Low-Power consumption Franz-Keldysh effect plasmonic modulator.
AB  - In this paper we report on a low energy consumption CMOS-compatible plasmonic
      modulator based on Franz-Keldysh effect in germanium on silicon. We performed
      integrated electro-optical simulations in order to optimize the main
      characteristics of the modulator. A 3.3 dB extinction ratio for a 30 um long
      modulator is demonstrated under 3 V bias voltage at an operation wavelength of
      1647 nm. The estimated energy consumption is as low as 20 fJ/bit. 

PMID- 24921822
TI  - Novel gas sensor combined active fiber loop ring-down and dual wavelengths
      differential absorption method.
AB  - A novel active fiber loop ring-down gas sensor combined with dual wavelengths
      differential absorption method is proposed. Two Distributed Feedback Laser Diodes
      (DFB LDs) with different wavelengths are employed. One LD whose wavelength
      covered with the absorption line of target gas is used for sensing. Another LD
      whose wavelength is centered outside the absorption line is used for reference.
      The gas absorption loss can be obtained by differencing the reference signal and
      sensing signal. Compared with traditional method of one wavelength employed, it
      can eliminate the influence of the cavity loss variety and photoelectric device
      drift in the system efficiently. An Erbium Doped Fiber Amplifier (EDFA) with
      Automatic Gain Control (AGC) is used to compensate the loss of the light in the
      ring-down cavity, which will increase the cavity round trips and improve the
      precision of gas detection. And two fiber Bragg gratings (FBGs) are employed to
      get rid of amplified spontaneous emission (ASE) spectrum noise as filters. The
      calibrating ethyne samples of different concentrations are measured with a 65 mm
      long gas cell in order to evaluate the effect of reference. The results show the
      relative deviation is found to be less than +/- 0.4% of 0.1% ethyne when a
      certain additional loss from 0 to 1.2dB is introduced to the cavity and the
      relative deviation of measured concentration is less than +/- 0.5% over 24 hours.

PMID- 24921823
TI  - Quantum dash based single section mode locked lasers for photonic integrated
      circuits.
AB  - We present the first demonstration of an InAs/InP Quantum Dash based single
      section frequency comb generator designed for use in photonic integrated circuits
      (PICs). The laser cavity is closed using a specifically designed Bragg reflector
      without compromising the mode-locking performance of the self pulsating laser.
      This enables the integration of single-section mode-locked laser in photonic
      integrated circuits as on-chip frequency comb generators. We also investigate the
      relations between cavity modes in such a device and demonstrate how the
      dispersion of the complex mode frequencies induced by the Bragg grating implies a
      violation of the equi-distance between the adjacent mode frequencies and,
      therefore, forbids the locking of the modes in a classical Bragg Device. Finally
      we integrate such a Bragg Mirror based laser with Semiconductor Optical Amplifier
      (SOA) to demonstrate the monolithic integration of QDash based low phase noise
      sources in PICs. 

PMID- 24921824
TI  - Impact of gain saturation on the mode instability threshold in high-power fiber
      amplifiers.
AB  - We present a coupled-mode model of transverse mode instability in high-power
      fiber amplifiers, which takes the effect of gain saturation into account. The
      model provides simple semi-analytical formulas for the mode instability
      threshold, which are valid also for highly saturated amplifiers. The model is
      compared to recently published detailed numerical simulations of mode
      instability, and we find reasonably good agreement with our simplified coupled
      mode model. 

PMID- 24921825
TI  - Control of integrated micro-resonator wavelength via balanced homodyne locking.
AB  - We describe and experimentally demonstrate a method for active control of
      resonant modulators and filters in an integrated photonics platform. Variations
      in resonance frequency due to manufacturing processes and thermal fluctuations
      are corrected by way of balanced homodyne locking. The method is compact,
      insensitive to intensity fluctuations, minimally disturbs the micro-resonator,
      and does not require an arbitrary reference to lock. We demonstrate long-term
      stable locking of an integrated filter to a laser swept over 1.25 THz. In
      addition, we show locking of a modulator with low bit error rate while the chip
      temperature is varied from 5 to 60 degrees  C. 

PMID- 24921826
TI  - Conical diffraction intensity profiles generated using a top-hat input beam.
AB  - The phenomenon of internal conical diffraction has been studied extensively for
      the case of laser beams with Gaussian intensity profiles incident along an optic
      axis of a biaxial material. This work presents experimental images for a top-hat
      input beam and offers a theoretical model which successfully describes the
      conically diffracted intensity profile, which is observed to differ qualitatively
      from the Gaussian case. The far-field evolution of the beam is predicted to be
      particularly interesting with a very intricate structure, and this is confirmed
      experimentally. 

PMID- 24921827
TI  - Self-formed cavity quantum electrodynamics in coupled dipole cylindrical
      waveguide systems.
AB  - An ideal optical cavity operates by confining light in all three dimensions. We
      show that a cylindrical waveguide can provide the longitudinal confinement
      required to form a two dimensional cavity, described here as a self-formed
      cavity, by locating a dipole, directed along the waveguide, on the interface of
      the waveguide. The cavity resonance modes lead to peaks in the radiation of the
      dipole-waveguide system that have no contribution due to the skew rays that exist
      in longitudinally invariant waveguides and reduce their Q-factor. Using a
      theoretical model, we evaluate the Q-factor and modal volume of the cavity formed
      by a dipole-cylindrical-waveguide system and show that such a cavity allows
      access to both the strong and weak coupling regimes of cavity quantum
      electrodynamics. 

PMID- 24921828
TI  - Heat accumulation during pulsed laser materials processing.
AB  - Laser materials processing with ultra-short pulses allows very precise and high
      quality results with a minimum extent of the thermally affected zone. However,
      with increasing average laser power and repetition rates the so-called heat
      accumulation effect becomes a considerable issue. The following discussion
      presents a comprehensive analytical treatment of multi-pulse processing and
      reveals the basic mechanisms of heat accumulation and its consequence for the
      resulting processing quality. The theoretical findings can explain the
      experimental results achieved when drilling microholes in CrNi-steel and for
      cutting of CFRP. As a consequence of the presented considerations, an estimate
      for the maximum applicable average power for ultra-shorts pulsed laser materials
      processing for a given pulse repetition rate is derived. 

PMID- 24921829
TI  - Generation of vector vortex beams with a small core multimode liquid core optical
      fiber.
AB  - We report on the generation of vector vortex beams using a 10-MUm core multimode
      liquid core optical fiber (LCOF) filled with CS(2). The first higher-order modes
      including radially, azimuthally and hybrid polarized vector modes, as well as the
      higher-order modes such as LP(21) mode and LP(31) mode are selectively excited by
      adjusting the incidence angle of the linearly polarized input Gaussian beam with
      respect to the fiber axis. The interferograms with single forklet verify the
      phase singularity of the vector beams generated. Compared to silica optical
      fibers, the vector vortex beams from the LCOFs have higher excitation efficiency
      and larger bending tolerance.

PMID- 24921830
TI  - Fracture characteristics of ceramic Nd:YAG.
AB  - The fracture of laser material in a ceramic Nd:YAG laser pumped by a fiber
      coupled laser diode was analyzed. The fracture of the laser material was found to
      occur when the critical temperature difference between the center of the material
      and the surface exceeded 355 degrees C. To quantitatively analyze the material
      fracture, the heat-generation length and heat-generation radius of the laser
      material were calculated and the critical pump power per unit volume was
      examined. Under lasing and non-lasing conditions, the fracture of laser material
      occurred at 24.41 kW/cm(3) and 19.53 kW/cm(3), respectively, for 2 at.% ceramic
      Nd:YAG and 25.57 kW/cm(3) and 20.47 kW/cm(3), respectively, for 4 at.% ceramic
      Nd:YAG.

PMID- 24921831
TI  - Terahertz plasmonic waveguide based on metal rod arrays for nanofilm sensing.
AB  - A high-aspect-ratio metallic rod array is demonstrated to generate and propagate
      highly confined terahertz (THz) surface plasmonic waves under end-fire
      excitation. The transverse modal power distribution and spectral properties of
      the bound THz plasmonic wave are characterized in two metallic rod arrays with
      different periods and in two configurations with and without attaching a
      subwavelength superstrate. The integrated metallic rod array-based waveguide can
      be used to sense the various thin films deposited on the polypropylene
      superstrate based on the phase-sensitive mechanism. The sensor exhibits different
      phase detection sensitivities depending on the modal power immersed in the air
      gaps between the metallic rods. Deep-subwavelength SiO(2) and ZnO nanofilms with
      an optical path difference of 252 nm, which is equivalent to lambda/3968 at 0.300
      THz, are used as analytes to test the integrated plasmonic waveguide. Analysis of
      the refractive index and thickness of molecular membranes indicates that the
      metallic rod array-based THz waveguide can integrate various biochip platforms
      for minute molecular detection, which is extremely less than the coherent length
      of THz waves.

PMID- 24921832
TI  - Laser link acquisition demonstration for the GRACE Follow-On mission.
AB  - We experimentally demonstrate an inter-satellite laser link acquisition scheme
      for GRACE Follow-On. In this strategy, dedicated acquisition sensors are not
      required-instead we use the photodetectors and signal processing hardware already
      required for science operation. To establish the laser link, a search over five
      degrees of freedom must be conducted (+/- 3 mrad in pitch/yaw for each laser
      beam, and +/- 1 GHz for the frequency difference between the two lasers). This
      search is combined with a FFT-based peak detection algorithm run on each
      satellite to find the heterodyne beat note resulting when the two beams are
      interfered. We experimentally demonstrate the two stages of our acquisition
      strategy: a +/- 3 mrad commissioning scan and a +/- 300 MUrad reacquisition scan.
      The commissioning scan enables each beam to be pointed at the other satellite to
      within 142 MUrad of its best alignment point with a frequency difference between
      lasers of less than 20 MHz. Scanning over the 4 alignment degrees of freedom in
      our commissioning scan takes 214 seconds, and when combined with sweeping the
      laser frequency difference at a rate of 88 kHz/s, the entire commissioning
      sequence completes within 6.3 hours. The reacquisition sequence takes 7 seconds
      to complete, and optimizes the alignment between beams to allow a smooth
      transition to differential wavefront sensing-based auto-alignment. 

PMID- 24921833
TI  - A high-responsivity photodetector absent metal-germanium direct contact.
AB  - We report a Ge-on-Si photodetector without doped Ge or Ge-metal contacts. Despite
      the simplified fabrication process, the device shows a responsivity of 1.14 A/W
      at -4 V reverse bias and 1.44 A/W at -12V, at 1550 nm wavelength. Dark current is
      less than 1uA under both bias conditions. We also demonstrate open eye diagrams
      at 40Gb/s. 

PMID- 24921834
TI  - Tamm plasmon-polariton with negative group velocity induced by a negative index
      meta-material capping layer at metal-Bragg reflector interface.
AB  - Influence of a negative refractive index meta-material (NIM) capping layer on
      properties of Tamm plasmon-polariton at the interface of metal-Bragg reflector
      structure is investigated. Conditions for excitation of the plasmon-polariton is
      determined from reflectivity mapping calculation and analyzed with cavity mode
      theory. For specific thicknesses of capping layers, Tamm plasmon-polariton with
      negative group velocity is revealed in a wide region of frequency. Different from
      backward optical propagation induced by negative effective-group-refractive-index
      in dispersive media, negative group velocity of Tamm plasmon-polariton results
      from opposite signs of cross-section-integrated field energy and Poynting vector.

PMID- 24921835
TI  - Design and simulation of omnidirectional reflective color filters based on metal
      dielectric-metal structure.
AB  - We propose omnidirectional reflective color filters based on metal-dielectric
      metal subwavelength grating structure. By particle swarm optimization, the
      structural parameters of three color filters (yellow, magenta, cyan) are
      obtained. The optimized filters can present the same perceived specular color at
      unpolarized illumination for a broad range of incident angles. The reflectance
      curves at different incident angles keep almost invariable and the color
      difference is less than 6 in CIEDE2000 formula up to 45 degrees . Angle
      insensitive properties including the incident angular tolerance, azimuthal
      angular tolerance and the polarization effect are investigated thoroughly to
      construct a real omnidirectional color filter. Through the analysis of the
      magnetic field, the physical origin is verified that the total absorption band at
      specific wavelength results from the localized surface plasmon resonance
      responsible for the angle insensitive spectral filtering. 

PMID- 24921836
TI  - Silent compartment syndrome in children: a report of five cases.
AB  - Compartment syndrome does not always present classically in the pediatric
      population, making clinical diagnosis uniquely challenging. The purpose of this
      study was to identify signs and symptoms of compartment syndrome that may help
      risk-stratify pediatric patients upon presentation, as well as to report outcomes
      of 'silent' compartment syndrome in children. A retrospective review of cases of
      'silent' compartment syndrome at a level I pediatric trauma center between 2000
      and 2010 was conducted. Patient demographics and clinical data were reviewed,
      including complications and patient outcomes. Radiographs taken at presentation,
      on intraoperative fluoroscopy, and at postoperative follow-up were reviewed for
      fracture type, and severity and outcome analyses. Five patients were found to
      have compartment syndrome without the presence of significant pain at rest or on
      passive range of motion. The study included three male and two female patients
      with a median age of 7 years. Three upper-extremity and two lower-extremity
      fractures were involved. The mean time from presentation to surgery was 14 h. At
      presentation, three of five patients had muscle paralysis, whereas at diagnosis
      of compartment syndrome, four of five had paralysis. Of the classic five P's, a
      maximum of two were found at diagnosis. The mean clinical follow-up period was 11
      months (2-26 months). Long-term complications from compartment syndrome were
      found in one of five patients, who at the most recent follow-up, continued to be
      debilitated. This study reviews a series of cases of 'silent' compartment
      syndrome and confirms its atypical presentation. It is recommended that caution
      be used when assessing fractures with high risk for compartment syndrome in
      children, especially those complicated by nerve injury, as they do not always
      present in the classic manner, with missed diagnosis leading to significant
      functional deficits. LEVEL OF EVIDENCE: IV.

PMID- 24921837
TI  - cGMP and cGMP-dependent protein kinase I pathway in dorsal root ganglia
      contributes to bone cancer pain in rats.
AB  - STUDY DESIGN: A prospective, randomized experimental research. OBJECTIVE: To
      demonstrate the role of cGMP (cyclic guanosine monophosphate)-cGKI (cGMP
      dependent protein kinase I) pathway in dorsal root ganglia (DRG) in bone cancer
      pain. SUMMARY OF BACKGROUND DATA: Treating bone cancer pain continues to possess
      a major clinical challenge because the specific cellular and molecular mechanisms
      underlying bone cancer pain remain elusive. cGMP and cGMP-dependent protein
      kinases pathway in DRG plays important role in nerve injury-induced
      hyperexcitability of DRG neurons, as well as neuropathic pain, however, whether
      this pathway participates in bone cancer pain is unknown. METHODS: The rat model
      of bone cancer pain was produced by intramedullary injection of rat breast cancer
      cells (Walker 256) into right tibia. Thermal hyperalgesia and mechanical
      allodynia were measured before and after administration of inhibitor of cGMP-cGKs
      pathway (Rp-8-pCPT-cGMPS). Immunofluorescence and reverse transcription
      polymerase chain reaction were used to reflect expression of cGKI in DRG neurons,
      whereas the concentration of cGMP in DRG was tested using enzyme-linked
      immunosorbent assay method. Whole-cell patch clamp was used to record the
      hyperexcitability of small neurons in DRG with or without cGKs inhibitor after
      tumor cell implantation (TCI). RESULTS: TCI treatment significantly increased the
      concentration of cGMP in DRG and activity of cGKs in DRG and the spinal cord. TCI
      treatment also induced upregulation of cGKI messenger ribonucleic acid and
      protein in DRG, as well as enhanced hyperexcitability in DRG neurons. Spinal
      administration of Rp-8-pCPT-cGMPS, cGMP-cGKs inhibitor, significantly suppressed
      TCI-induced activation of cGMP-cGKI signaling, and hyperexcitability of DRG
      neurons. Meanwhile, in vivo intrathecal delivery of the Rp-8-pCPT-cGMPS
      significantly prevented and suppressed TCI-induced hyperalgesia and allodynia.
      CONCLUSION: From these results, we confirm that TCI treatment activates cGMP-cGKI
      signaling pathway and continuing activation of this pathway in DRG is required
      for hyperalgesia and/or hyperalgesia and allodynia after TCI treatment. LEVEL OF
      EVIDENCE: N/A.

PMID- 24921838
TI  - Does a kaolin-impregnated hemostatic dressing reduce intraoperative blood loss
      and blood transfusions in pediatric spinal deformity surgery?
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To evaluate the
      hemostatic benefits of using a kaolin-impregnated dressing during pediatric
      spinal deformity correction surgery. SUMMARY OF BACKGROUND DATA: Minimizing blood
      loss and transfusions are clear benefits for patient safety. A technique common
      in both severe trauma and combat medicine that has not been reported in the spine
      literature is wound packing with a kaolin-impregnated hemostatic dressing.
      METHODS: Estimated blood loss and transfusion amounts were analyzed in a total of
      117 retrospectively identified cases. The control group included 65 patients (46
      females, 19 males, 12.7+/-4.5 yr, 10.2+/-4.8 levels fused) who received standard
      operative care with gauze packing between June 2007 and March 2010. The treatment
      group included 52 patients (33 females, 19 males, 13.9+/-3.2 yr, 10.4+/-4.3
      levels fused) who underwent intraoperative packing with QuikClot Trauma Pads
      (QCTP, Z-Medica Corporation) for all surgical procedures from July 2010 to August
      2011. No other major changes in the use of antifibrinolytics or perioperative,
      surgical, or anesthesia technique were noted. Statistical differences were
      analyzed using analysis of covariance in R with P value of less than 0.05. The
      statistical model included sex, age, weight, scoliosis type, the number of
      vertebral levels fused, and surgery duration as covariates. RESULTS: The
      treatment group had 40% less intraoperative estimated blood loss than the control
      group (974 mL vs. 1620 mL) (P<0.001). Patients who received the QCTP treatment
      also had 42% less total perioperative transfusion volume (499 mL vs. 862 mL)
      (P<0.01). CONCLUSION: The use of a kaolin-impregnated intraoperative trauma pad
      seems to be an effective and inexpensive method to reduce intraoperative blood
      loss and transfusion volume in pediatric spinal deformity surgery. LEVEL OF
      EVIDENCE: 3.

PMID- 24921839
TI  - Re: Kawano O, Maeda T, Mori E, et al. Influence of spinal cord compression and
      traumatic force on the severity of cervical spinal cord injury associated with
      ossification of the posterior longitudinal ligament.

PMID- 24921840
TI  - In response.

PMID- 24921841
TI  - Fate of osteophytes and sclerosis in fused segments after lumbar fusion.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the fate of
      sclerosis and anterior osteophytes in the fused segments after instrumented
      lumbar fusion for degenerative lumbar disorders. SUMMARY OF BACKGROUND DATA:
      Sclerosis and osteophytosis are well-known radiographical findings, but little is
      known of their significance with regard to spontaneous resorption after spine
      fusion. METHODS: Thirty patients (9 males, 21 females; 60 vertebra; mean age of
      66.9 yr [45-86 yr]) were divided into a posterolateral fusion group (n = 14, 28
      vertebrae) and a posterior lumbar interbody fusion group (n = 16, 32 vertebrae).
      Using serial radiographs obtained preoperatively; postoperatively at 3, 6, 12,
      and 24 months; and last follow-up, sclerotic areas of each involved vertebra were
      mapped and osteophyte lengths were measured. RESULTS: Sclerosis and osteophytes
      decreased with time for the instrumented fusion. The decrease in sclerotic areas
      and osteophytes length was observed as early as 3 months postoperatively, and the
      significant changes between each time point were noted in initial 3- and 6-month
      intervals. In terms of the type of surgery, similar changes were noted in the
      posterolateral fusion and posterior lumbar interbody fusion groups. CONCLUSION:
      Resorption of osteophytes and sclerosis after instrumented spine fusion were
      observed. Significant resorption was noted at 3 and 6 months postoperatively. As
      well, most graft bone would be incorporated in postoperative 6 months. Resorption
      of osteophytes and sclerosis after instrumented spine fusion could be helpful to
      confirm the successful union. LEVEL OF EVIDENCE: 4.

PMID- 24921842
TI  - Radiographic spinopelvic parameters in skeletally mature patients with
      Scheuermann disease.
AB  - STUDY DESIGN: Retrospective radiographical analysis of sagittal spinopelvic
      parameters in skeletally mature patients with Scheuermann disease (SD).
      OBJECTIVE: To analyze anatomical and positional parameters of spinopelvic
      sagittal alignment in mature patients with SD. SUMMARY OF BACKGROUND DATA:
      Sagittal spinopelvic alignment has already been characterized in normal subjects
      and deviations in sagittal parameters have been reported for various spinal
      pathologies. No study has investigated spinopelvic parameters in SD. METHODS:
      Standing posteroanterior and lateral radiographs of the skeletally mature
      patients with SD were analyzed. Immature patients and those with other spinal
      pathologies were excluded from the study. Pelvic positional and anatomic
      parameters and spinal parameters were measured. Pelvic incidence (PI) was
      compared with the values reported for healthy individuals. Correlations between
      the measured parameters were analyzed. RESULTS: Forty patients met the inclusion
      criteria. Sixteen females and 24 males (mean age, 25 yr) were analyzed. The mean
      PI in this group was 40 degrees  and was significantly lower than that reported
      for healthy adults and adolescents (P < 0.0001) and not significantly different
      than the values reported for healthy children (P = 0.44). Patients with atypical
      (thoracolumbar) SD had lower PI than those with typical (thoracic) form (41
      degrees  vs. 38 degrees ; P = 0.09). There was no correlation between PI and LL,
      thoracic kyphosis, or thoracolumbar kyphosis. CONCLUSION: This study demonstrated
      that skeletally mature patients with SD have significantly lower PI than healthy
      adults. There was no correlation between PI and LL in individuals with SD. This
      challenges the role of PI in predicting the proper values of LL in this group of
      patients. Further studies are needed to investigate whether impaired spinopelvic
      alignment is a cause or a result of SD. LEVEL OF EVIDENCE: 3.

PMID- 24921843
TI  - Use of the S-hook for Pelvic Fixation in Rib-Based Treatment of Early-Onset
      Scoliosis: A Multicenter Study.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: The purpose of this study was to
      evaluate how several preoperative variables affect the outcome using the rib-to
      pelvis S-hook constructs of a rib-based distraction implant (Vertical Expandable
      Prosthetic Titanium Rib). SUMMARY OF BACKGROUND DATA: Rib-to-pelvis fixation with
      S-hooks is one of the options for distal anchoring of rib-based distraction
      growing rod construct to control early-onset spinal deformity. Since the initial
      report, the indications of pelvic fixation with S-hooks have been extended and
      modified. METHODS: This is an institutional review board-approved retrospective
      study of patients who underwent rib-based growing rod system surgery-rib-to
      pelvis construct with Dunn-McCarthy S-hook. Data evaluation included history,
      physical examination, preoperative and postoperative radiographs, surgical
      variables, and complications. RESULTS: Sixty-five patients were evaluated; 38
      were male and 27 were female. Mean age at initial procedure was 71 months. The
      mean follow-up was 46 months. There was a statistically significant improvement
      of the immediate postoperative Cobb angle and the last follow-up Cobb angle (P <
      0.0001). Fifty percent of the patients (32/65) had S-hook-related complications.
      The most common complication was sliding of the S-hook out of the iliac crest,
      followed by infection, neuropathic pain, distal migration of more than 2 cm,
      fracture of the hook, and bursitis. The complications were related to the
      preoperative ambulatory status, the use of end-to-end rod connectors, surgical
      time, and not positioning the hook over the central one-third of the iliac crest
      at the initial implantation. CONCLUSION: The use of the S-hook as a pelvic
      attachment of the rib-based system is indicated in nonambulatory patients with
      progressive, early-onset scoliosis curve with a lack of adequate anchor at the
      lumbar spine. Several technical factors should be considered to reduce the
      complication rate. LEVEL OF EVIDENCE: 3.

PMID- 24921844
TI  - Vertigo-related cerebral blood flow changes on magnetic resonance imaging.
AB  - STUDY DESIGN: A prospective study using magnetic resonance imaging on a
      consecutive cohort of patients with cervical vertigo. OBJECTIVE: To
      quantitatively investigate the cerebral blood flow (CBF) changes associated with
      cervical vertigo by using 3-dimensional pseudocontinuous arterial spin labeling.
      SUMMARY OF BACKGROUND DATA: Previous studies reported blood flow velocity
      reduction in posterior circulation during vertigo. However, the detailed
      information of CBF related to cervical vertigo has not been provided. METHODS: A
      total of 33 patients with cervical vertigo and 14 healthy volunteers were
      recruited in this study. Three-dimensional pseudocontinuous arterial spin
      labeling was performed on each subject to evaluate the CBF before and after the
      cervical hyperextension-hyperflexion movement tests, which was used to induce
      cervical vertigo. Repeated-measures analysis of variance was conducted to assess
      the effect of subjects and tests. RESULTS: There were time effects of CBF in the
      territory of bilateral superior cerebellar artery, bilateral posterior cerebral
      artery, bilateral middle cerebral artery, and right anterior cerebral artery, but
      no group effect was observed. The analysis of CBF revealed a significant main
      effect of tests (P=0.024) and participants (P=0.038) in the dorsal pons.
      CONCLUSION: Cervical vertigo onset may be related to CBF reduction in the dorsal
      pons, which sequentially evokes the vestibular nuclei. LEVEL OF EVIDENCE: 2.

PMID- 24921845
TI  - Brown tumor of the spine in patients with primary hyperparathyroidism.
AB  - STUDY DESIGN: Retrospective case series and literature review. OBJECTIVE: To
      describe our experience in diagnosis and management of patients with spine brown
      tumor (osteitis fibrosa cystica) as the initial manifestation of primary
      hyperparathyroidism and also to review the pertinent literature. SUMMARY OF
      BACKGROUND DATA: The spine can be involved through reparative processes such as
      giant cell reparative granuloma and brown tumor, which lead to formation of
      lesions that can simulate tumors on neuroimaging. Brown tumor, an uncommon focal
      giant cell lesion, is a nonneoplastic and reactive process due to bone resorption
      and localized osseous lesion caused by primary or secondary hyperparathyroidism.
      METHODS: Among the cases of spine giant cell lesions treated surgically by the
      authors (2000-2013), there were 4 cases of spine brown tumor in patients with
      primary hyperparathyroidism. Clinical, radiological, histopathologic, and
      surgical data of these 4 cases were collected, and the patients were followed
      from 5 to 7 years after the surgical intervention. RESULTS: There were 2 male and
      2 female patients with age range of 16 to 52 years. The lesions were located in
      cervical (1 case), thoracic (1 case), and lumbar (2 cases) spine regions.
      Clinical presentations included neck and low back pain, radicular pain,
      paraparesis, and sphincter dysfunction. Surgical removal of the spine lesions was
      achieved in all cases. Spine fusion and instrumentation was done in 3 cases.
      Parathyroidectomy was performed in all 4 cases. CONCLUSION: Spine involvement
      with brown tumor in patients with primary hyperparathyroidism is rare and may be
      the first manifestation of hyperparathyroidism. Brown tumor should be
      differentiated from other giant cell lesions involving the spine. Long-term
      surgical outcome was satisfactory with no recurrence. LEVEL OF EVIDENCE: 4.

PMID- 24921846
TI  - The effect of cervical posterior foraminotomy on segmental range of motion in the
      setting of total disc arthroplasty.
AB  - STUDY DESIGN: Human cadaveric biomechanical analysis. OBJECTIVE: To investigate
      the effect on cervical spine segmental stability that results from a posterior
      foraminotomy after cervical disc arthroplasty (CDA). SUMMARY OF BACKGROUND DATA:
      Posterior foraminotomy offers the ability to decompress cervical nerves roots
      while avoiding the need to extend a previous fusion or revise an arthroplasty to
      a fusion. However, the safety of a foraminotomy in the setting of CDA is unknown.
      METHODS: Segmental nondestructive range of motion (ROM) was analyzed in 9 human
      cadaveric cervical spine specimens. After intact testing, each specimen was
      sequentially tested according to the following 4 experimental groups: group 1=C5
      C6 CDA, group 2=C5-C6 CDA with unilateral C5-C6 foraminotomy, group 3=C5-C6 CDA
      with bilateral C5-C6 foraminotomy, and group 4=C5-C6 CDA with C5-C6 and C4-C5
      bilateral foraminotomy. RESULTS: No differences in ROM were found between the
      intact, CDA, and foraminotomy specimens at C4-C5 or C6-C7. There was a step-wise
      increase in C5-C6 axial rotation from the intact state (8 degrees ) to group 4
      (12 degrees ), although the difference did not reach statistical significance. At
      C5-C6, the degree of lateral bending remained relatively constant. Flexion and
      extension at C5-C6 was significantly higher in the foraminotomy specimens, groups
      2 (18.1 degrees ), 3 (18.6 degrees ), and 4 (18.2 degrees ), compared with the
      intact state, 11.2 degrees . However, no ROM difference was found within
      foraminotomy groups (2-4) or between the foraminotomy groups and the CDA group
      (group 1), 15.3 degrees . CONCLUSION: Our results indicate that cervical
      stability is not significantly decreased by the presence, number, or level of
      posterior foraminotomies in the setting of CDA. The addition of foraminotomies to
      specimens with a pre-existing CDA resulted in small and insignificant increases
      in segmental ROM. Therefore, biomechanically, posterior
      foraminotomy/foraminotomies may be considered a safe and viable option in the
      setting of recurrent or adjacent level radiculopathy after cervical disc
      replacement. LEVEL OF EVIDENCE: N/A.

PMID- 24921847
TI  - Psychosocial factors and surgical outcomes: are elderly depressed patients less
      satisfied with surgery?
AB  - STUDY DESIGN: Longitudinal cohort study. OBJECTIVE: In this study, we set out to
      assess the effect of preoperative depression on patient satisfaction after
      revision lumbar surgery. SUMMARY OF BACKGROUND DATA: Patient satisfaction ratings
      are increasingly being used in health care as a proxy for quality of care. In the
      elderly, affective disorders such as depression have been shown to influence
      patient-reported outcomes and self-interpretation of health status. METHODS: A
      total of 69 patients aged 65 years or older undergoing revision neural
      decompression and instrumented fusion for same-level recurrent stenosis
      associated back and leg pain were included in this study. Preoperative Zung self
      rating depression score, comorbidities, and postoperative satisfaction with
      surgical care and outcome were assessed for all patients. Baseline and 2-year
      visual analogue scale (VAS)-leg pain, VAS-back pain, Oswestry Disability Index,
      Short Form-12 physical component score and Short Form-12 mental component score,
      as well as health-state utility (EuroQol 5D) were assessed. Factors associated
      with patient satisfaction after surgical procedures were assessed via
      multivariate logistic regression analysis. RESULTS: Compared with baseline, there
      was a statistically significant improvement in VAS-back pain 2.76+/-2.73
      (pseudarthrosis [1.94+/-2.81], adjacent segment disease [4.35+/-3.16]), same
      level recurrent stenosis [2+/-2.23]), VAS-leg pain 2.66+/-4.12, (adjacent segment
      disease [2.24+/-4.46] and same-level recurrent stenosis [3+/-3.78]). Two-year
      Oswestry Disability Index improved after surgery for pseudarthrosis (4.05+/
      7.65), adjacent segment disease (6+/-13.63) and same-level recurrent stenosis
      (4.54+/-5.97). In a multivariate logistical regression model, increasing
      preoperative Zung self-rating depression scale scores were independently
      associated with patient dissatisfaction 2 years after revision lumbar surgery,
      (P<0.001). CONCLUSION: This study demonstrates that independent of surgical
      effectiveness, baseline depression influence patient satisfaction with health
      care, 2 years after revision lumbar surgery. Quality improvement initiatives
      using patient satisfaction as a proxy for quality of care should account for
      patients' baseline depression as a potential confounder especially in this age
      group. LEVEL OF EVIDENCE: 3.

PMID- 24921848
TI  - National trends and in-hospital outcomes in HIV-positive patients undergoing
      spinal fusion.
AB  - STUDY DESIGN: A retrospective analysis of population-based national hospital
      discharge data collected for the Nationwide Inpatient Sample. OBJECTIVE: To
      examine the trends and in-hospital outcomes of patients with human
      immunodeficiency virus (HIV) infection undergoing spinal fusion on a national
      level. SUMMARY OF BACKGROUND DATA: Highly active antiretroviral therapy has
      provided healthier lives and prolonged the life expectancy of HIV-positive
      patients. However, few previous studies have reported trends and outcomes of HIV
      positive patients undergoing spinal surgery. METHODS: Clinical data were derived
      from the US Nationwide Inpatient Sample between 2000 and 2009. Patients who
      underwent spinal fusion were identified. Data regarding HIV, patient- and health
      care system-related characteristics, comorbidities, in-hospital complications,
      and mortality were retrieved and analyzed. In-hospital outcomes were compared
      between HIV-positive and -negative patients and analyzed with the use of
      multivariate logistic regression. RESULTS: A total of 5,070 HIV-positive patients
      underwent spinal fusion in the United States during the last decade. From 2000 to
      2009, population-adjusted incidence of HIV-positive patients who underwent spinal
      fusion has increased more than 3-fold (0.094 per 100,000 in 2000 to 0.303 per
      100,000 in 2009; P < 0.001). Comparison between HIV-positive and -negative
      patients showed that HIV-positive patients had a significantly higher respiratory
      complication rate (6.2% vs. 3.2%), wound-related complication rate (2.7% vs.
      1.7%), overall in-hospital complication rate (12.2% vs. 9.5%), and in-hospital
      mortality rate (1.6% vs. 0.3%), as well as longer hospital stay (6.6 d vs. 4.2
      d). The risk of in-hospital mortality was 3.53 times higher in HIV-positive
      patients after controlling for other factors (95% confidence interval, 2.02-6.14;
      P < 0.001). CONCLUSION: During the last decade, the incidence of HIV-positive
      patients undergoing spinal fusion has increased in the United States. In this
      study, HIV infection was an independent risk factor for in-hospital mortality in
      patients undergoing spinal fusion. LEVEL OF EVIDENCE: 3.

PMID- 24921849
TI  - Safety of topical vancomycin for pediatric spinal deformity: nontoxic serum
      levels with supratherapeutic drain levels.
AB  - STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: To establish if drain
      levels exceed the minimum inhibitory concentrations for common pathogens
      (methicillin-resistant Staphylococcus aureus, methicillin-sensitive
      Staphylococcus aureus, and Propionibacterium acnes-2 MUg/mL; Staphylococcus
      epidermidis, Enterococcus faecalis-4 MUg/mL). Evaluate the safety of topical
      vancomycin in pediatric patients undergoing spinal deformity surgery and
      determine if postoperative serum levels approach toxicity (25 MUg/mL). SUMMARY OF
      BACKGROUND DATA: The application of topical vancomycin powder has decreased
      postoperative wound infections in retrospective analyses in the adult population
      with minimal local and systemic risks. The safety and efficacy of vancomycin
      powder has not been completely evaluated in the pediatric population after
      deformity surgery. METHODS: Topical vancomycin powder (1 g) was applied during
      wound closure after instrumented posterior spinal fusion. All patients received
      intravenous perioperative antibiotics and a subfascial drain was used. Serum and
      drain vancomycin levels were collected immediately postoperatively and during the
      first 2 postoperative days (PODs). Complications were recorded. RESULTS: The
      study population consisted of 25 patients with a mean age of 13.5 years (9.5-17.1
      yr) and mean +/- standard deviation body weight of 44.5 +/- 18 kg. Underlying
      diagnoses included: adolescent idiopathic scoliosis (12), neuromuscular scoliosis
      (10), and kyphosis (3). Mean serum vancomycin levels trended downward from 2.5
      MUg/mL (POD 0) to 1.9 MUg/mL (POD 1) to 1.1 MUg/mL (POD 2). Mean drain levels
      also trended downward from 403 MUg/mL (POD 0) to 251 MUg/mL (POD 1) to 115 MUg/mL
      (POD 2). No vancomycin toxicity or deep wound infections were observed. One
      patient with neuromuscular scoliosis developed a superficial wound dehiscence
      that was managed with dressing changes. CONCLUSION: Topical application of
      vancomycin powder in pediatric spinal deformity surgery produced local levels
      well above the minimum inhibitory concentration for common pathogens and serum
      levels below the toxicity threshold (25 MUg/mL). There were no deep wound or
      antibiotic related complications. LEVEL OF EVIDENCE: 3.

PMID- 24921850
TI  - Cement augmentation in a thoracolumbar fracture model: reduction and stability
      after balloon kyphoplasty versus vertebral body stenting.
AB  - STUDY DESIGN: In vitro biomechanical investigation. OBJECTIVE: To assess
      differences in kyphosis after balloon kyphoplasty (BKP) or vertebral body
      stenting (VBS). SUMMARY OF BACKGROUND DATA: Cement augmentation techniques allow
      early mobilization in patients with osteoporotic thoracolumbar fractures.
      Biomechanically, the grade of reduction and preservation are as important as in
      nonosteoporotic fractures. With BKP, negative effects of balloon deflation on the
      reduction and whether specific combinations of materials may preserve the
      reduction are as yet unclear. METHODS: Twelve bisegmental human thoracolumbar
      specimens (6*T12-L2, 6*L3-L5; age at death, 76.3 yr; range, 63-89 yr; female:male
      ratio, 3:3; bone mineral density, 68.1 g/cm; mean, 12.9 g/cm) were tested in a
      spine simulator with pure moments of 7.5 Nm to assess primary and secondary
      stability. After flexibility testing of the intact specimens, an eccentric
      compression force induced standardized fractures, which were reduced using either
      BKP or VBS against a flexional moment of 2.5 Nm. Primary and secondary stability
      were assessed using range of motion in a spine tester. The specimens were tested
      after each of 3 periods of cyclic flexion loading. The kyphotic angle of the
      index vertebra was measured radiographically. RESULTS: The 2 techniques achieved
      comparable reduction against a relatively high bending moment in this model.
      Neither technique restored the stability of the intact state; with increasing
      loads, the range of motion continuously increased to the level of fractured
      specimen to the level of the fractured specimen. Although the deflation effect on
      the kyphotic angle was lower with VBS (P<=0.05), there were no significant
      differences between the techniques relative to angle restoration. CONCLUSION:
      Both augmentation techniques are able to restore vertebral body height after
      thoracolumbar fractures. The deflation effect on the kyphotic angle was less with
      VBS than with BKP. High flexion moments during implantation limit the
      effectiveness of reduction using cement augmentation methods. LEVEL OF EVIDENCE:
      N/A.

PMID- 24921852
TI  - Obese patients report modest weight loss after surgery for lumbar spinal
      stenosis: a study from the Swedish spine register.
AB  - STUDY DESIGN: SWESPINE, the Swedish Spine Register, was used for this cohort
      study. OBJECTIVE: Our primary aim was to determine weight change in obese
      patients after surgery for lumbar spinal stenosis (LSS). Our secondary aim was to
      study any possible associations between weight loss after surgery and improvement
      in patient-related outcome measures (PROMs). SUMMARY OF BACKGROUND DATA: Only
      meager evidence is available as to how surgery for LSS affects weight and whether
      weight loss is associated with improvement in PROMs after surgery for LSS.
      METHODS: All obese patients who underwent surgery for LSS from January 1, 2006
      through June 30, 2008 with a completed 2-year follow-up in SWESPINE were
      included. Data for weight were collected before surgery and then 1 and 2 years
      after surgery. The cohort was divided into 3 subclasses (weight stable, weight
      loss, or weight gain). RESULTS: Totally, 538 obese patients were enrolled. Mean
      weight loss was 1.9 kg (95% confidence interval, 1.5-2.3) 1 year after surgery
      and 2.0 kg (95% confidence interval, 1.5-2.4) after 2 years after surgery. Only
      8% of the patients reported a clinically important weight loss (>=10%). No
      significant differences in PROMs were observed. The weight-stable group reported
      a mean improvement of 0.22 (standard deviation, 0.36) in EQ-5D, 14 (18) units in
      the Oswestry Disability Index, 18 (33) units in back pain (visual analogue
      scale), and 23 (36) units in leg pain (visual analogue scale). The corresponding
      changes in the weight-loss group were 0.23 (0.35) in EuroQol 5D, 15 (19) in
      Oswestry Disability Index, 27 (29) in back pain, and 31 (36) in leg pain.
      CONCLUSION: Modest weight loss was reported 1 and 2 years postsurgery; a small
      proportion (8%) of these patients reported a clinically important weight loss at
      the 2-year follow-up. The weight loss was unrelated to changes in PROMs. LEVEL OF
      EVIDENCE: 3.

PMID- 24921851
TI  - Three-dimensional characterization of torsion and asymmetry of the intervertebral
      discs versus vertebral bodies in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To compare the relative
      contribution of the vertebral bodies and intervertebral discs with the 3
      dimensional spinal deformity in adolescent idiopathic scoliosis. SUMMARY OF
      BACKGROUND DATA: There is an ongoing discussion about the causal role of skeletal
      growth processes in the etiopathogenesis of adolescent idiopathic scoliosis.
      Contradictory findings have been reported on the individual contribution of the
      vertebral bodies as compared with the discs to the coronal deformity. As far as
      we know, the true 3-dimensional deformity of the discs and vertebral bodies have
      not yet been described. METHODS: High-resolution computed tomographic scans of 77
      patients with severe adolescent idiopathic scoliosis were included. Torsion and
      anterior-posterior and right-left asymmetry of each individual vertebral body and
      intervertebral disc were studied from T2 to L5, using semiautomatic analysis
      software. True transverse sections were reconstructed along the anterior
      posterior and right-left axis of all endplates. These "endplate-vectors" were
      calculated semiautomatically, taking rotation and tilt into account. Torsion was
      defined as the difference in axial rotation between 2 subsequent endplates.
      Asymmetry was defined as the relative anterior-posterior or right-left height
      difference of the discs and the vertebrae. RESULTS: There were at least 3 times
      more torsion, anterior overgrowth, and coronal wedging in the discs than in the
      vertebrae in the thoracic as well as in the (thoraco) lumbar curves (P<0.001).
      These values correlated significantly with the Cobb angle (r>=0.37; P<0.001).
      Anterior overgrowth and coronal asymmetry were greater in the apical regions
      whereas torsion was most pronounced in the transitional segments between the
      curves. CONCLUSION: The discs contribute more to 3-D deformity than the bony
      structures, and there is significant regional variability. This suggests an
      adaptive rather than an active phenomenon. LEVEL OF EVIDENCE: 2.

PMID- 24921853
TI  - Advantageous new conic cannula for spine cement injection.
AB  - STUDY DESIGN: Experimental study to characterize the influence of the cannula
      geometry on both, the pressure drop and the cement flow velocity established
      along the cannula. OBJECTIVE: To investigate how the new experimental geometry of
      cannulas can affect the extravertebral injection pressure and the velocity
      profiles established along the cannula during the injection process. SUMMARY OF
      BACKGROUND DATA: Vertebroplasty procedure is being used to treat vertebral
      compression fractures. Vertebra infiltration is favored by the use of suitable:
      (1) syringes or injector devices; (2) polymer or ceramic bone cements; and (3)
      cannulas. However, the clinical use of ceramic bone cement has been limited due
      to press-filtering problems. Thus, new approaches concerning the cannula geometry
      are needed to minimize the press-filtering of calcium phosphate-based bone
      cements and thereby broaden its possible applications. METHODS: Straight, conic,
      and combined conic-straight new cannulas with different proximal and distal both
      length and diameter ratios were drawn with computer-assisted design software. The
      new geometries were theoretically analyzed by: (1) Hagen-Poisseuille law; and (2)
      computational fluid dynamics. Some experimental models were manufactured and
      tested for extrusion in order to confirm and further advance the theoretical
      results. RESULTS: The results confirm that the totally conic cannula model,
      having proximal to distal diameter ratio equal 2, requires the lowest injection
      pressure. Furthermore, its velocity profile showed no discontinuity at all along
      the cannula length, compared with other known combined proximal and distal
      straight cannulas, where discontinuity was produced at the proximal-distal
      transition zone. CONCLUSION: The conclusion is that the conic cannulas: (a)
      further reduced the extravertebral pressure during the injection process; (b)
      showed optimum fluid flow velocity profiles to minimize filter-pressing problems,
      especially when ceramic cements are used; and (c) can be easily manufactured. In
      this sense, the new conic cannulas should favor the use of calcium phosphate bone
      cements in the spine. LEVEL OF EVIDENCE: N/A.

PMID- 24921854
TI  - Anterior vertebral body tethering for idiopathic scoliosis: two-year results.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To report the 2-year results of
      the initial cohort undergoing anterior vertebral body tethering (VBT). SUMMARY OF
      BACKGROUND DATA: Anterior VBT is a promising new technique with abundant
      preclinical studies but very few clinical results. It is a growth modulation
      technique, which utilizes patients' growth to attain progressive correction of
      their scoliosis. We report 2-year results of the initial cohort undergoing this
      procedure. METHODS: After obtaining institutional review board approval, we
      retrospectively reviewed our first 11 consecutive patients who underwent anterior
      VBT with 2-year follow-up. We collected pertinent preoperative, intraoperative,
      and most recent clinical and radiographical data. Student t test and Fisher exact
      test were utilized to compare different time points. RESULTS: Eleven patients
      with thoracic idiopathic scoliosis (8 females) were identified, with a mean age
      of 12.3 +/- 1.6 years. Preoperatively, all were skeletally immature (Sanders mean
      = 3.4 +/- 1.1; Risser mean = 0.6 +/- 1.1). All underwent tethering of an average
      of 7.8 +/- 0.9 (range: 7-9) levels, with the most proximal being T5 and the most
      distal L2. Preoperative thoracic Cobb angle averaged 44.2 +/- 9.0 degrees  and
      corrected to 20.3 +/- 11.0 degrees  on first erect, with progressive improvement
      at 2 years (Cobb angle = 13.5 +/- 11.6 degrees , % correction = 70%; P <
      0.00002). Similarly, the preoperative lumbar curve of 25.1 +/- 8.7 degrees 
      demonstrated progressive correction (first erect = 14.9 +/- 4.9 degrees , 2 yr =
      7.2 +/- 5.1 degrees , % correction = 71%; P < 0.0002). Thoracic axial rotation as
      measured by a scoliometer went from 12.4 +/- 3.3 degrees  preoperatively to 6.9
      +/- 3.4 degrees  at the most recent measurement (P < 0.01). No major
      complications were observed. As anticipated, 2 patients returned to the operating
      room at 2 years postoperatively for loosening of the tether to prevent
      overcorrection. CONCLUSION: Anterior VBT is a promising technique for skeletally
      immature patients with idiopathic scoliosis. This technique can be performed
      safely and can result in progressive correction. LEVEL OF EVIDENCE: 4.

PMID- 24921855
TI  - Pulmonary function recovery demonstrated by ventilation-perfusion scan after
      posterior vertebral column resection for severe adolescent idiopathic scoliosis:
      a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a case in which a patient
      regained pulmonary function, assessed by ventilation-perfusion scans, after
      undergoing posterior vertebral column resection (VCR) to correct severe
      adolescent idiopathic scoliosis (AIS) with associated pulmonary dysfunction.
      SUMMARY OF BACKGROUND DATA: Pulmonary improvement after corrective surgery for
      AIS has been reported. Ventilation-perfusion scans are useful for assessing
      pulmonary function. However, these scans have not been used to examine the
      recovery of pulmonary function after VCR for severe AIS with pulmonary
      dysfunction. METHODS: A patient was described in whom ventilation-perfusion scans
      were used to examine improvements in impaired air ventilation and blood perfusion
      after VCR surgery for severe AIS. The relevant literature was reviewed. RESULTS:
      An 18-year-old male came to Keio University Hospital with exertional dyspnea
      associated with severe AIS. Radiographs showed severe scoliosis of 91 degrees  at
      T6-T12, and hypokyphosis of 6 degrees  at T5-T12. Computed tomographic scans
      showed narrowing of the thoracic cage on the convex side of the main thoracic
      curve, with the vertebral bodies at the apex of the curve obstructing the right
      main bronchus. Pulmonary function tests revealed a percent vital capacity of 44%
      and percent forced expiratory volume in 1 second of 76%. A ventilation-perfusion
      scan showed decreased air ventilation and blood perfusion in the right lung. The
      patient underwent posterior correction surgery, which used segmental pedicle
      screws with a VCR at T9. The scoliosis was corrected to 28 degrees , and the
      kyphosis to 14 degrees . Postoperative computed tomographic scans showed
      expansion of the right main bronchus. A ventilation-perfusion scan conducted 1
      year after surgery showed clear improvement in both ventilation and blood
      perfusion in the right lung. The patient's forced expiratory volume in 1 second
      had increased to 91%. CONCLUSION: This is the first report in which ventilation
      perfusion scans were used to examine improvements in impaired air ventilation and
      blood perfusion after VCR surgery in a patient with severe AIS. LEVEL OF
      EVIDENCE: N/A.

PMID- 24921857
TI  - Full domain-decomposition scheme for diffuse optical tomography of large-sized
      tissues with a combined CPU and GPU parallelization.
AB  - The common approach to diffuse optical tomography is to solve a nonlinear and ill
      posed inverse problem using a linearized iteration process that involves repeated
      use of the forward and inverse solvers on an appropriately discretized domain of
      interest. This scheme normally brings severe computation and storage burdens to
      its applications on large-sized tissues, such as breast tumor diagnosis and brain
      functional imaging, and prevents from using the matrix-fashioned linear
      inversions for improved image quality. To cope with the difficulties, we propose
      in this paper a parallelized full domain-decomposition scheme, which divides the
      whole domain into several overlapped subdomains and solves the corresponding
      subinversions independently within the framework of the Schwarz-type iterations,
      with the support of a combined multicore CPU and multithread graphics processing
      unit (GPU) parallelization strategy. The numerical and phantom experiments both
      demonstrate that the proposed method can effectively reduce the computation time
      and memory occupation for the large-sized problem and improve the quantitative
      performance of the reconstruction. 

PMID- 24921858
TI  - Light-modulating pressure sensor with integrated flexible organic light-emitting
      diode.
AB  - Organic light-emitting diodes (OLEDs) are used almost exclusively for display
      purposes. Even when implemented as a sensing component, it is rarely in a manner
      that exploits the possible compliance of the OLED. Here it is shown that OLEDs
      can be integrated into compliant mechanical micro-devices making a new range of
      applications possible. A light-modulating pressure sensor is considered, whereby
      the OLED is integrated with a silicon membrane. It is shown that such devices
      have potential and advantages over current measurement techniques. An analytical
      model has been developed that calculates the response of the device. Ray tracing
      numerical simulations verify the theory and show that the design can be optimized
      to maximize the resolution of the sensor. 

PMID- 24921856
TI  - Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful
      whole-body vibration.
AB  - STUDY DESIGN: In vivo study defining expression of the neurotrophins, brain
      derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical
      intervertebral discs after painful whole-body vibration (WBV). OBJECTIVE: The
      goal of this study is to determine if BDNF and NGF are expressed in cervical
      discs after painful WBV in a rat model. SUMMARY OF BACKGROUND DATA: WBV is a
      possible source of neck pain and has been implicated as increasing the risk for
      disc disorders. Typically, aneural regions of painful human lumbar discs exhibit
      hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc
      degeneration and pain. BDNF and NGF are upregulated in painfully degenerate
      lumbar discs and hypothesized to contribute to this pathology. METHODS: Male
      Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham
      exposures, followed by 7 days of rest. Cervical discs were collected for analysis
      of BDNF and NGF expression through RT-qPCR and Western blot analysis.
      Immunohistochemistry also evaluated their regional expression in the disc.
      RESULTS: Vibration significantly increases BDNF messenger ribonucleic acid (mRNA)
      levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both
      BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold,
      respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035)
      levels are significantly correlated with the degree of behavioral sensitivity
      (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the
      extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most
      increased in the inner annulus fibrosus and nucleus pulposus. CONCLUSION: The
      increases in BDNF and NGF in the cervical discs after painful vibration are
      observed in typically aneural regions of the disc, consistent with reports of its
      hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not
      explicitly investigated. Neurotrophin expression also correlates with behavioral
      sensitivity, suggesting a role for both neurotrophins in the development of disc
      pain. LEVEL OF EVIDENCE: N/A.

PMID- 24921859
TI  - Conoscopic analysis of electric field driven planar aligned nematic liquid
      crystal.
AB  - This paper illustrates the conoscopic observation of a molecular reconstruction
      occurring across a nematic liquid crystal (NLC) medium in the presence of an
      external electric field. Conoscopy is an optical interferometric method, employed
      to determine the orientation of an optic axis in uniaxial crystals. Here a planar
      aligned NLC medium is used, and the topological changes with respect to various
      applied voltages are monitored simultaneously. Homogenous planar alignment is
      obtained by providing suitable surface treatments to the ITO coated cell walls.
      The variation in the conoscopic interferometric patterns clearly demonstrates the
      transition from planar to homeotropic state through various intermediate states. 

PMID- 24921860
TI  - Simultaneous reconstruction of multiple depth images without off-focus points in
      integral imaging using a graphics processing unit.
AB  - The reconstruction of multiple depth images with a ray back-propagation algorithm
      in three-dimensional (3D) computational integral imaging is computationally
      burdensome. Further, a reconstructed depth image consists of a focus and an off
      focus area. Focus areas are 3D points on the surface of an object that are
      located at the reconstructed depth, while off-focus areas include 3D points in
      free-space that do not belong to any object surface in 3D space. Generally,
      without being removed, the presence of an off-focus area would adversely affect
      the high-level analysis of a 3D object, including its classification,
      recognition, and tracking. Here, we use a graphics processing unit (GPU) that
      supports parallel processing with multiple processors to simultaneously
      reconstruct multiple depth images using a lookup table containing the shifted
      values along the x and y directions for each elemental image in a given depth
      range. Moreover, each 3D point on a depth image can be measured by analyzing its
      statistical variance with its corresponding samples, which are captured by the
      two-dimensional (2D) elemental images. These statistical variances can be used to
      classify depth image pixels as either focus or off-focus points. At this stage,
      the measurement of focus and off-focus points in multiple depth images is also
      implemented in parallel on a GPU. Our proposed method is conducted based on the
      assumption that there is no occlusion of the 3D object during the capture stage
      of the integral imaging process. Experimental results have demonstrated that this
      method is capable of removing off-focus points in the reconstructed depth image.
      The results also showed that using a GPU to remove the off-focus points could
      greatly improve the overall computational speed compared with using a CPU. 

PMID- 24921861
TI  - Multiple-channel guided mode resonance Brewster filter with controllable spectral
      separation.
AB  - In this work, a single-layer, multiple-channel guided mode resonance (GMR)
      Brewster filter with controllable spectral separation is proposed using the plane
      waveguide method and rigorous coupled-wave analysis. Based on the normalized
      eigenvalue equation, the controllability of the spectral separation is analyzed
      when the fill ratio of the grating layer is changed while its effective index is
      identical to that of the substrate. The location and the separation between
      resonances can be specifically controlled by modifying the fill ratio of the
      grating layer. In contrast to the ordinary GMR filter, where the location of the
      resonances is material dependent, it is demonstrated that the spectral separation
      for the first and second resonances can be linearly controlled by altering the
      fill ratio of the grating layer. In addition, the maximal shift of the second
      resonance is up to 5% of the first resonant wavelength using the single-layer
      Brewster filter. 

PMID- 24921862
TI  - Prism-pair interferometer for precise measurement of the refractive index of
      optical glass by using a spectrum lamp.
AB  - A prism-pair interferometer for a spectrum lamp was developed for precise
      measurement of the refractive index of a prism of optical glass. Previously we
      reported the prism-pair interferometer with a He-Ne laser light source, resulting
      in a measurement uncertainty of 1.1*10-6. However, most of the refractive-index
      values managed by optical glass manufacturers are conventionally measured with
      spectrum lamps. We have optimized the prism-pair interferometer for spectrum
      lamps and implemented a signal-processing technique from Fourier-transform
      spectroscopy. When the refractive index is measured, the wavelength of the
      spectrum lamp is simultaneously calibrated by part of the interferometer, so that
      the resulting refractive index is traceable to a national standard of length. The
      combined standard uncertainty for a refractive index measured with the e-line
      (546 nm) of a Hg lamp is 6.9*10-6.

PMID- 24921863
TI  - High-efficiency fused-silica reflection grism.
AB  - A fused-silica reflection grism (combination of grating and prism) based on the
      phenomenon of total internal reflection (TIR), and used in the -1st order, is
      designed and fabricated. The grism is etched directly into the fused-silica
      prism, which greatly facilitates the use of the TIR grating as no other angle
      coupling devices are involved. The grating profile is optimized by the use of the
      rigorous coupled-wave analysis method. Diffraction efficiency of larger than 99%
      at a wavelength of 980 nm for TM-polarized waves can be theoretically obtained.
      Two-beam interference lithography and inductively coupled plasma etching
      techniques are used to manufacture such grism. Diffraction efficiencies of larger
      than 95% are experimentally demonstrated.

PMID- 24921864
TI  - Fast and noninterpolating method for subpixel displacement analysis of digital
      speckle images using phase shifts of spatial frequency spectra.
AB  - A fast noninterpolation method for calculating displacement of digital speckle
      images with subpixel precision was introduced. In this method, the precise
      displacement is obtained from phase shifts of spatial frequency spectra of two
      digital speckle images instead of digital correlation calculation. First, digital
      speckle images before and after displacement are windowed and fast Fourier
      transform is performed. Then, phase shifts of different spatial frequencies are
      linearly fitted in spectral space using the least square method, and a coarse
      displacement value is directly calculated according to the phase shift theorem of
      Fourier transform. By a window technique and iterative procedure, the influence
      of finite image size on the accuracy of the results is eliminated, and the
      accurate displacement is obtained finally. It is significant that the method
      obtains the subpixel-precision displacement without any interpolation operations.
      The test results show that the method has high computing efficiency, high
      precision, and good robustness to low image quality. 

PMID- 24921865
TI  - Validation of short-pulse-laser-based measurement setup for absolute spectral
      irradiance responsivity calibration.
AB  - This paper describes the validation process of mode-locked lasers in the "tunable
      lasers in photometry" (TULIP) setup at Physikalisch-Technische Bundesanstalt
      (PTB) regarding spectral irradiance responsivity calibrations. Validation has
      been carried out in the visible spectral range, 400-700 nm, with two different
      photometer heads and in the long wavelength range, 690-780 nm, with a filtered
      radiometer. A comparison of the results against those from two different
      validated measurement setups has been carried out for validation. For the visible
      spectral range, the comparison is conducted against the data obtained from a lamp
      based monochromator setup for spectral irradiance responsivity calibrations and
      against the photometric values (integral quantity) measured at the photometric
      bench setup of PTB. For the long wavelength range, comparisons against results
      from two different lamp-based monochromator measurement setups were made.
      Additionally, the effect of different radiation bandwidths on interference
      oscillations has been determined for a filter radiometer without a diffuser. A
      procedure for the determination of the optimum bandwidth of the setup for the
      respective measurement device is presented.

PMID- 24921866
TI  - Virtual camera calibration using optical design software.
AB  - Camera calibration is a critical step in many vision applications. It is a
      delicate and complex process that is highly sensitive to environmental
      conditions. This paper presents a novel virtual calibration technique that can be
      used to study the impact of various factors on the calibration parameters. To
      highlight the possibilities of the method, the calibration parameters' behavior
      has been studied regarding the effects of tolerancing and temperature for a
      specific lens. This technique could also be used in many other promising areas to
      make calibration in the laboratory or in the field easier. 

PMID- 24921867
TI  - Passively mode-locked fiber laser by using monolayer chemical vapor deposition of
      graphene on D-shaped fiber.
AB  - We demonstrate a monolayer graphene saturable absorber (SA) based on D-shaped
      fiber for operation of the mode-locked fiber laser. The monolayer graphene is
      grown by chemical vapor deposition (CVD) on Cu substrate and transferred onto the
      polymer, and then covered with D-shaped fiber, which allows light-graphene
      interaction via the evanescent field of the fiber. Due to the side-coupled
      interaction, the length of graphene is long enough to avoid optical power-induced
      thermal damage. Using such a graphene-based SA, stable mode-locked solitons with
      4.5 nm spectral bandwidth and 713 fs pulsewidth at the 1563 nm wavelength have
      been obtained under 280 mW pump power. The influence of total cavity dispersion
      on the optical spectrum and pulse is also investigated by adding different
      lengths of single-mode fiber in the laser cavity.

PMID- 24921868
TI  - Distributed optical fiber dynamic magnetic field sensor based on
      magnetostriction.
AB  - A distributed optical fiber sensor is introduced which is capable of quantifying
      multiple magnetic fields along a 1 km sensing fiber with a spatial resolution of
      1 m. The operation of the proposed sensor is based on measuring the
      magnetorestrictive induced strain of a nickel wire attached to an optical fiber.
      The strain coupled to the optical fiber was detected by measuring the strain
      induced phase variation between the backscattered Rayleigh light from two
      segments of the sensing fiber. A magnetic field intensity resolution of 0.3 G
      over a bandwidth of 50-5000 Hz was demonstrated.

PMID- 24921869
TI  - Feature weighting algorithms for classification of hyperspectral images using a
      support vector machine.
AB  - The support vector machine (SVM) is a widely used approach for high-dimensional
      data classification. Traditionally, SVMs use features from the spectral bands of
      hyperspectral images with each feature contributing equally to the
      classification. In practical applications, although affected by noise, slight
      contributions can also be obtained from deteriorated bands. Thus, compared with
      feature reduction or equal assignment of weights to all the features, feature
      weighting is a trade-off choice. In this study, we examined two approaches to
      assigning weights to SVM features to increase the overall classification
      accuracy: (1) "CSC-SVM" refers to a support vector machine with compactness and a
      separation coefficient feature weighting algorithm, and (2) "SE-SVM" refers to a
      support vector machine with a similarity entropy feature weighting algorithm.
      Analyses were conducted on a public data set with nine selected land-cover
      classes. In comparison with traditional SVMs and other classical feature
      weighting algorithms, the proposed weighting algorithms increase the overall
      classification accuracy, and even better results could be obtained with few
      training samples. 

PMID- 24921870
TI  - Light-scattering effectiveness of two-dimensional disordered surface textures in
      thin-film silicon solar cells.
AB  - To compare the light-scattering effectiveness of surface-textured solar cells of
      various design parameters such as density, diameter, refractive index, and
      location, this study used a new parameter, optical path length gain (OPLG), that
      is more sensitive than Haze. By modeling two-dimensional disordered textures as a
      structure that comprises many randomly distributed, small, spherical scatterers,
      ray-tracing simulations of surface-textured thin-film silicon solar cells were
      performed. The simulation results suggest that: (1) the optimal scatterer
      diameter for hydrogenated amorphous silicon (a-Si:H) solar cells is ~50 nm,
      producing an average OPLG of 3.5; and (2) the optimal scatterer diameter for a
      Si:H/MUc-Si:H (hydrogenated microcrystalline silicon) tandem cells is ~75 nm,
      producing an average OPLG of 3.4 and an increase in the bandwidth of the
      absorption spectrum of 14.5%.

PMID- 24921871
TI  - Anisotropic effective medium properties from interacting Ag nanoparticles in
      silicon dioxide.
AB  - Films containing a layer of Ag nanoparticles embedded in silicon dioxide were
      produced by RF magnetron sputtering. Optical transmittance measurements at
      several angles of incidence (from normal to 75 degrees ) revealed two surface
      plasmon resonance (SPR) peaks, which depend on electric field direction: one in
      the ultraviolet and another red-shifted from the dilute Ag/SiO2 system resonance
      at 410 nm. In order to investigate the origin of this anisotropic behavior, the
      structural properties were determined by transmission electron microscopy,
      revealing the bidimensional plane distribution of Ag nanoparticles with nearly
      spherical shape as well as the filling factor of metal in the composite. A simple
      model linked to these experimental parameters allowed description of the most
      relevant features of the SPR positions, which, depending on the field direction,
      were distinctly affected by the coupling of oscillations between close
      nanoparticles, as described by a modified Drude-Lorentz dielectric function
      introduced into the Maxwell-Garnett relation. This approach allowed prediction of
      the resonance for light at 75 degrees  incidence from the SPR position for light
      at normal incidence, in good agreement with experimental observation.

PMID- 24921872
TI  - Radius measurement by laser confocal technology.
AB  - A laser confocal radius measurement (LCRM) method is proposed for high-accuracy
      measurement of the radius of curvature (ROC). The LCRM uses the peak points of
      confocal response curves to identify the cat eye and confocal positions
      precisely. It then accurately measures the distance between these two positions
      to determine the ROC. The LCRM also uses conic fitting, which significantly
      enhances measurement accuracy by restraining the influences of environmental
      disturbance and system noise on the measurement results. The experimental results
      indicate that LCRM has a relative expanded uncertainty of less than 10 ppm for
      both convex and concave spheres. Thus, LCRM is a feasible method for ROC
      measurements with high accuracy and concise structures.

PMID- 24921873
TI  - Coherent broadband light generation with a double-path configuration.
AB  - We generate broadband light by focusing two femtosecond pulses into a Raman
      active crystal. By reflecting Raman sideband beams together with the two driving
      beams back to the same crystal (with a slight spatial offset), we generate
      sidebands covering a broader spectral range, compared to a single pass. In this
      novel double-path configuration, multiple Raman sideband beams interact with each
      other since the phase-matching condition is automatically fulfilled. This scheme
      enables an enhanced cascaded coherent anti-Stokes scattering process and also
      doubles the interaction length, thus it allows one to use relatively weak energy
      pump pulses and thereby avoid optical damage. 

PMID- 24921874
TI  - Capture and display mismatch compensation for real-time digital holographic
      interferometry.
AB  - Optical holographic interferometry (HI) is realized by two well-known techniques:
      double exposure holographic interferometry (DEHI) and real-time holographic
      interferometry (RTHI). However, the digital version of HI is typically realized
      numerically by DEHI. The main problem in digital implementation of RTHI is the
      lack of commercially available cameras and spatial light modulators with the same
      pixel size. This mismatch results in lateral and transversal magnifications of an
      object wavefront reconstruction. In real-time digital HI the reconstruction of an
      object in an initial state has to be superimposed on top of the loaded object. In
      this work, we present and analyze five approaches to overcome the mismatch
      problem, and the performance of these procedures is numerically quantified and
      compared. The experimental suitability of these approaches is investigated. 

PMID- 24921875
TI  - Performance of line-scan Raman microscopy for high-throughput chemical imaging of
      cell population.
AB  - We evaluate the performance of line-scan Raman microscopy (LSRM), a versatile
      label-free technique, for high-throughput chemical imaging of cell population. We
      provide detailed design and configuration of a home-built LSRM system developed
      in our laboratory. By exploiting parallel acquisition, the LSRM system achieves a
      significant throughput advantage over conventional point-scan Raman microscopy by
      projecting a laser line onto the sample and imaging the Raman scattered light
      from the entire line using a grating spectrograph and a charge-coupled device
      (CCD) camera. Two-dimensional chemical maps can be generated by scanning the
      projected line in the transverse direction. The resolution in the x and y
      direction has been characterized to be ~600-800 nm for 785 nm laser excitation.
      Our system enables rapid classification of microparticles with similar shape,
      size, and refractive index based on their chemical composition. An equivalent
      imaging throughput of 100 microparticles/s for 1 MUm polystyrene beads has been
      achieved. We demonstrate the application of LSRM to imaging bacterial spores by
      identifying endogenous calcium dipicolinate. We also demonstrate that LSRM
      enables the study of intact microalgal cells at the colonial level and the
      identification of intra- and extracellular chemical constituents and metabolites,
      such as chlorophyll, carotenoids, lipids, and hydrocarbons. We conclude that LSRM
      can be an effective and practical tool for obtaining endogenous microscopic
      chemical and molecular information from cell population.

PMID- 24921876
TI  - Laser-generated broadband antireflection structures for freeform silicon lenses
      at terahertz frequencies.
AB  - We present a flexible technology to generate broadband antireflection (AR)
      structures for the terahertz (THz) frequency range on planar and curved surfaces
      of silicon optics. Ultrashort laser pulses are used to ablate the surface to form
      a pattern of conical pillars with a period of 30 MUm. These subwavelength
      structures act as an effective medium with gradual transition of the refractive
      index from air to silicon, which reduces the Fresnel reflection losses. The
      characterization with the THz time-domain spectroscopy system shows an AR effect
      for a frequency range of 0.1-1.5 THz with a maximum enhancement of the spectral
      amplitude by ca. 32% at 0.4 THz for planar surfaces. In addition, we demonstrate
      laser-generated AR structures on convex silicon lenses of both photoconductive
      emitter and detector devices. Here, the THz pulse amplitude can be increased by
      about 28%, and single frequencies even show an improvement of the spectral
      amplitude up to 58%.

PMID- 24921877
TI  - Decoupling scattering and absorption of turbid samples using a simple empirical
      relation between coefficients of the Kubelka-Munk and radiative transfer
      theories.
AB  - Efforts are underway to better understand the absorption properties of micro- and
      nano-sized particles due to their potential in various photonic applications.
      However, most of these particles exhibit strong scattering in the spectral
      regions of interest in addition to absorption. Due to strong interference from
      scattering, the absorption of these turbid samples cannot be directly measured
      using conventional spectroscopy techniques. The optical properties of these
      particles are also different from that of the bulk due to quantum confinement and
      plasmon resonance effects and cannot be inferred from their bulk properties. By
      measuring the total transmittance and total reflectance (diffuse and collimated)
      of turbid samples and using an empirical relation between the coefficients of the
      Kubelka-Munk and radiative transfer theories, we have demonstrated a method to
      calculate the absorption and reduced scattering coefficients of turbid samples.
      This method is capable of extracting the absorption coefficient of turbid samples
      with an error of 2%. Using this method, we have decoupled the specific absorption
      and specific reduced scattering coefficients of commercially available micro
      sized iron oxide particles. The current method can be used to measure the optical
      properties of irregularly shaped particle dispersions, which are otherwise
      difficult to estimate theoretically. 

PMID- 24921878
TI  - Designing photonic quasi-crystal fibers of various folds: onto optimization of
      efficiency and bandwidth of second harmonic generation.
AB  - We design photonic quasi-crystal fibers (PQFs) of six-, eight-, ten-, and twelve
      folds for determining the optimized efficiency as well as the bandwidth of second
      harmonic generation (SHG). We report a maximum SHG relative efficiency of 941.36%
      W-1 cm-2 for a twelve-fold PQF of 2 MUm pitch. The detailed numerical results
      reveal that, while the relative efficiency increases appreciably, the phase
      matching bandwidth increases marginally, as and when the number of folds
      increases. As the primary interest of this work is to enhance the relative
      efficiency, we focus our analysis with a twelve-fold PQF for which the efficiency
      turns a maximum. In line with the practical feasibility of poling, we keep the
      pitch at 7 MUm and report an optimized relative efficiency and phase-matching
      bandwidth as 95.28% W-1 cm-2 and 50.51 nm.cm, respectively.

PMID- 24921879
TI  - Sub-nanoradiant beam pointing monitoring and stabilization system for controlling
      input beam jitter in gravitational wave interferometers.
AB  - In this paper, a simple and effective control system to monitor and suppress the
      beam jitter noise at the input of an optical system, called a beam pointing
      control (BPC) system, will be described, showing the theoretical principle and an
      experimental demonstration for the application of large-scale gravitational wave
      (GW) interferometers (ITFs), in particular for the Advanced Virgo detector. For
      this purpose, the requirements for the control accuracy and the sensing noise
      will be computed by taking into account the Advanced Virgo optical configuration,
      and the outcomes will be compared with the experimental measurement obtained in
      the laboratory. The system has shown unprecedented performance in terms of
      control accuracy and sensing noise. The BPC system has achieved a control
      accuracy of ~10-8 rad for the tilt and ~10-7 m for the shift and a sensing noise
      of less than 1 n  rad/?Hz, which is compliant with the Advanced Virgo GW ITF
      requirements.

PMID- 24921880
TI  - Spatial coating inhomogeneity of highly reflective mirrors determined by cavity
      ringdown measurements.
AB  - The inhomogeneity of high-reflectivity mirror coatings is a potential error
      source in the application of the cavity ringdown technique. Here, the ringdown
      times for different transverse modes were recorded. Together with the observed
      spatial distribution of these modes the ringdown times can be used to
      approximately locate the position of coating defects. A simple model based on a
      weighted sum of Hermite-Gaussian mode functions is used to explain the
      experimental results. 

PMID- 24921881
TI  - Application of multi-correlation-scale measurement matrices in ghost imaging via
      sparsity constraints.
AB  - Sampling and reconstruction techniques are of special interest and importance in
      ghost imaging. Up to now, the transverse correlation scale of measurement
      matrices are usually constant. This paper explores a new possibility of
      constructing highly efficient measurement matrices with multi-correlation scales.
      Comparisons between the simulational and experimental results show that the multi
      correlation-scale measurement matrices are highly efficient and accurate in
      sampling and image reconstruction and have a better antinoise ability than the
      existing constant-correlation-scale measurement matrices. 

PMID- 24921882
TI  - Analysis of the relationship between fringe angle and three-dimensional
      profilometry system sensitivity.
AB  - The relationship between projector-camera baseline and the phase variation
      direction of fringe patterns is one of the essential characteristics in a three
      dimensional (3D) profilometry system, although it has been ignored. This paper
      indicates that a 3D profilometry system will be most sensitive to object depth
      change when the phase variation direction of the fringe patterns is parallel to
      the baseline, which is analyzed in systems based on both the triangulation and
      stereovision principles. An efficient method is proposed to achieve the most
      sensitivity by projecting a set of fringe patterns of different phase variation
      directions. Experimental results demonstrate our analysis and the proposed
      determination method. 

PMID- 24921883
TI  - Drift-eliminating method of intensity demodulation on a chirped fiber grating
      strain sensor.
AB  - It is quite possible to detect the strain of a sample based on a chirped fiber
      grating (CFG) sensor, which has a wider bandwidth of light signal than a fiber
      Bragg grating. Usually, environmental factors play negative roles in the process
      of intensity demodulation. A drift-eliminating method of CFG intensity
      demodulation has been created and tested in our lab. Three CFG sensors were
      involved in this research. Two of them with close wavelength bands connected in
      series were used as a strain sensing unit; the third one was used as a
      referencing grating working within the reflective wavelength spectrum of the
      other two. It is shown that the signal ratio of the sensing unit and the
      referencing grating is a linear function of the loading strain. The linearity is
      as high as 99.79%. 

PMID- 24921884
TI  - Fabrication and characterization of a deep ultraviolet wire grid polarizer with a
      chromium-oxide subwavelength grating.
AB  - A wire grid polarizer comprised of chromium oxide is designed for a micro
      lithography system using an ArF excimer laser. Optical properties for some
      material candidates are calculated using a rigorous coupled-wave analysis. The
      chromium oxide wire grid polarizer with a 90 nm period is fabricated by a double
      patterning technique using KrF lithography and dry etching. The extinction ratio
      of the grating is greater than 20 dB (100:1) at a wavelength of 193 nm.
      Differences between the calculated and experimental results are discussed.

PMID- 24921885
TI  - Computationally efficient video restoration for Nyquist sampled imaging sensors
      combining an affine-motion-based temporal Kalman filter and adaptive Wiener
      filter.
AB  - In this paper, we present a computationally efficient video restoration algorithm
      to address both blur and noise for a Nyquist sampled imaging system. The proposed
      method utilizes a temporal Kalman filter followed by a correlation-model based
      spatial adaptive Wiener filter (AWF). The Kalman filter employs an affine
      background motion model and novel process-noise variance estimate. We also
      propose and demonstrate a new multidelay temporal Kalman filter designed to more
      robustly treat local motion. The AWF is a spatial operation that performs
      deconvolution and adapts to the spatially varying residual noise left in the
      Kalman filter stage. In image areas where the temporal Kalman filter is able to
      provide significant noise reduction, the AWF can be aggressive in its
      deconvolution. In other areas, where less noise reduction is achieved with the
      Kalman filter, the AWF balances the deconvolution with spatial noise reduction.
      In this way, the Kalman filter and AWF work together effectively, but without the
      computational burden of full joint spatiotemporal processing. We also propose a
      novel hybrid system that combines a temporal Kalman filter and BM3D processing.
      To illustrate the efficacy of the proposed methods, we test the algorithms on
      both simulated imagery and video collected with a visible camera. 

PMID- 24921886
TI  - Combining transverse field detectors and color filter arrays to improve
      multispectral imaging systems.
AB  - This work focuses on the improvement of a multispectral imaging sensor based on
      transverse field detectors (TFDs). We aimed to achieve a higher color and
      spectral accuracy in the estimation of spectral reflectances from sensor
      responses. Such an improvement was done by combining these recently developed
      silicon-based sensors with color filter arrays (CFAs). Consequently, we
      sacrificed the filter-less full spatial resolution property of TFDs to narrow
      down the spectrally broad sensitivities of these sensors. We designed and
      performed several experiments to test the influence of different design features
      on the estimation quality (type of sensor, tunability, interleaved polarization,
      use of CFAs, type of CFAs, number of shots), some of which are exclusive to TFDs.
      We compared systems that use a TFD with systems that use normal monochrome
      sensors, both combined with multispectral CFAs as well as common RGB filters
      present in commercial digital color cameras. Results showed that a system that
      combines TFDs and CFAs performs better than systems with the same type of
      multispectral CFA and other sensors, or even the same TFDs combined with
      different kinds of filters used in common imaging systems. We propose CFA+TFD
      based systems with one or two shots, depending on the possibility of using longer
      capturing times or not. Improved TFD systems thus emerge as an interesting
      possibility for multispectral acquisition, which overcomes the limited accuracy
      found in previous studies. 

PMID- 24921887
TI  - Continuum fusion solutions for replacement target models in electro-optic
      detection.
AB  - The additive target model is used routinely in the statistical detection of
      opaque targets, despite its phenomenological inaccuracy. The more appropriate
      replacement target model is seldom used, because the standard method for
      producing a detection algorithm from it proves to be intractable, unless narrow
      restrictions are imposed. Now, the recently developed continuum fusion (CF)
      methodology allows an expanded solution set to the general replacement target
      problem. It also provides a mechanism for producing approximate solutions for the
      standard approach. We illustrate the principles of CF by using them to generate
      both types of answers for the correct detection model. 

PMID- 24921888
TI  - Enhancement of imagery of objects with highly dynamic brightness and large
      rotational motion.
AB  - We report on application of multi-frame super-resolution (SR) to sampling limited
      imagery that models space objects (SOs). The difficulties of multi-frame image
      processing of SOs include abrupt illumination changes and complex in scene SO
      motion. These conditions adversely affect the accuracy of motion estimation
      necessary for resolution enhancement. We analyze the motion estimation errors
      from the standpoint of an optical flow (OF) interpolation error metric and show
      dependence of the object tracking accuracy on brightness changes and on the pixel
      displacement values between subsequent images. Despite inaccuracies of motion
      estimation, we demonstrate spatial acuity enhancement of the pixel limited
      resolution of model SO motion imagery by applying a SR algorithm that accounts
      for OF errors. In addition to visual inspection, image resolution improvement
      attained in the experiments is assessed quantitatively; a 1.8* resolution
      enhancement is demonstrated. 

PMID- 24921889
TI  - Video rate nine-band multispectral short-wave infrared sensor.
AB  - Short-wave infrared (SWIR) imaging sensors are increasingly being used in
      surveillance and reconnaissance systems due to the reduced scatter in haze and
      the spectral response of materials over this wavelength range. Typically SWIR
      images have been provided either as full motion video from framing panchromatic
      systems or as spectral data cubes from line-scanning hyperspectral or
      multispectral systems. Here, we describe and characterize a system that bridges
      this divide, providing nine-band spectral images at 30 Hz. The system integrates
      a custom array of filters onto a commercial SWIR InGaAs array. We measure the
      filter placement and spectral response. We demonstrate a simple simulation
      technique to facilitate optimization of band selection for future sensors. 

PMID- 24921890
TI  - Characterization of the AWARE 10 two-gigapixel wide-field-of-view visible imager.
AB  - System requirements for many military electro-optic and IR camera systems reflect
      the need for both wide-field-of-view situational awareness as well as high
      resolution imaging for target identification. In this work we present a new
      imaging system architecture designed to perform both functions simultaneously and
      the AWARE 10 camera as an example at visible wavelengths. We first describe the
      basic system architecture and user interface followed by a laboratory
      characterization of the system optical performance. We then describe a field
      experiment in which the camera was used to identify several maritime targets at
      varying range. The experimental results indicate that users of the system are
      able to correctly identify ~10 m targets at between 4 and 6 km with 70% accuracy.

PMID- 24921891
TI  - Compact camera for multispectral and conventional imaging based on patterned
      filters.
AB  - A multispectral camera concept is presented. The concept is based on using a
      patterned filter in the focal plane, combined with scanning of the field of view.
      The filter layout has stripes of different bandpass filters extending
      orthogonally to the scan direction. The pattern of filter stripes is such that
      all bands are sampled multiple times, while minimizing the total duration of the
      sampling of a given scene point. As a consequence, the filter needs only a small
      part of the area of an image sensor. The remaining area can be used for
      conventional 2D imaging. A demonstrator camera has been built with six bands in
      the visible and near infrared, as well as a panchromatic 2D imaging capability.
      Image recording and reconstruction is demonstrated, but the quality of image
      reconstruction is expected to be a main challenge for systems based on this
      concept. An important advantage is that the camera can potentially be made very
      compact, and also low cost. It is shown that under assumptions that are not
      unreasonable, the proposed camera concept can be much smaller than a conventional
      imaging spectrometer. In principle, it can be smaller in volume by a factor on
      the order of several hundred while collecting the same amount of light per
      multispectral band. This makes the proposed camera concept very interesting for
      small airborne platforms and other applications requiring compact spectral
      imagers. 

PMID- 24921892
TI  - Designing pictorial stimuli for perceptual experiments.
AB  - The effects of design decisions in the development of systems that generate
      images for human consumption, such as cameras and displays, are often evaluated
      using real-world images. However, human observers can react differently to
      complex pictorial stimuli over the course of a lengthy experiment. This study was
      conducted to develop understanding of the optimal design of pictorial stimuli for
      effective and efficient perceptual experiments. The goals were to understand the
      impact of image content on visual attention and consistency of experimental
      results and apply this understanding to develop guidelines for pictorial target
      design for perceptual image comparison experiments. The efficacy of the proposed
      guidelines was evaluated. While the fixation consistency results were generally
      as expected, fixation consistency did not always equate to experimental response
      consistency. Along with scene complexity, the image modifications and the
      difficulty of the image equivalency decisions played a role in the experimental
      response. 

PMID- 24921893
TI  - Analytical direct solutions of the Risley prism systems for tracking and
      pointing.
AB  - The Risley prism systems, which had many different configurations, are only
      composed of two wedge prisms. The expressions of the direction cosines of the
      refractive ray of the two wedge prisms are given by nonparaxial ray tracing in a
      local coordinate referenced to the wedge prism, and the power of ray deviation of
      the two wedge prisms are shown by curves for systems using prisms of different
      materials and opening angles. The analytical direct solutions of the Risley prism
      systems are derived from the expressions of the direction cosines of the wedge
      prism through the coordinate transformation, and are also deduced from the two
      exact orientations for the same pointing position of precision tracking and
      pointing systems, which arise from applications of the Risley prisms to free
      space communications. The exact expressions for the problem of precision tracking
      are generalized to investigate the synthesis of tracking a given target, i.e., to
      track a desirable path on some plane perpendicular to the optical axis of the
      system by controlling the circular motion of the two prisms. 

PMID- 24921894
TI  - Imaging systems and applications: introduction to the feature.
AB  - Imaging systems have numerous applications in industrial, military, consumer, and
      medical settings. Assembling a complete imaging system requires the integration
      of optics, sensing, image processing, and display rendering. This issue features
      original research ranging from design of stimuli for human perception, optics
      applications, and image enhancement to novel imaging modalities in both color and
      infrared spectral imaging, gigapixel imaging as well as a systems perspective to
      imaging. 

PMID- 24921895
TI  - Breast cancer stage at diagnosis among medically underserved women screened
      through the Texas Breast and Cervical Cancer Services.
AB  - The Texas Breast and Cervical Cancer Services (BCCS) program was established to
      address the socioeconomic disparities in stage at diagnosis and outcomes among
      breast cancer patients. This study examines the impact of Texas BCCS on stage at
      diagnosis among low socioeconomic status (SES) breast cancer patients. This is a
      retrospective analysis of women aged 40-64 years who were screened and diagnosed
      with breast cancer through the Texas BCCS program (participants) as compared with
      similar women living in low-SES census tracts and diagnosed outside the program
      (comparison group) during 1995-2008. Incident cases among the participants were
      compared with the comparison group as well. Stage at diagnosis was also analyzed
      separately for the years 1995-2002 and 2003-2008 in order to estimate the effect
      of BCCS-related Medicaid expansion in 2002. Over the study period of 1995-2008,
      BCCS participants had a 1.23 (P value<0.0001) times higher odds, and BCCS
      incident cases had 40% (P value<0.0001) lower odds of advanced stage at diagnosis
      as compared with the comparison group. A statistically significant difference in
      stage at diagnosis between the participants and the comparison group only existed
      for the 2003-2008 (post-Medicaid) period (odds ratio: 1.39, P value<0.0001).
      Texas BCCS program acts as a source of diagnosis and treatment access to many
      suspected cancer cases, especially since the 2002 Medicaid expansion, leading to
      more advanced stage at diagnosis among the BCCS cases as compared with other low
      SES cases. Significant expansion of the program to serve a higher proportion of
      the eligible population is needed to achieve its goals as a screening program.

PMID- 24921896
TI  - Facilitating Glaucoma Diagnosis With Intereye Retinal Nerve Fiber Layer Asymmetry
      Using Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: To test whether increased intereye retinal nerve fiber layer (RNFL)
      asymmetry may be indicative of glaucoma. To determine the best statistical
      methods and intereye RNFL cutoffs for differentiating between normal and glaucoma
      subjects to better alert clinicians to early glaucomatous damage. METHODS: Sixty
      six primary open-angle glaucoma (OAG) and 40 age-matched normal subjects had both
      eyes imaged at the Massachusetts Eye and Ear Infirmary with a commercially
      available spectral-domain optical coherence tomography (OCT) machine. Statistical
      methodologies were used to find cutoffs that achieved the best sensitivities and
      specificities for differentiating OAG from normal subjects. RESULTS: Intereye
      RNFL asymmetry for global average, all quadrants, and all sectors was
      significantly greater in OAG than normal subjects. Intereye RNFL asymmetry for
      global average showed the greatest statistical difference (P<0.001) between OAG
      (23.64 +/- 14.90 MUm) and normal eyes (3.58 +/- 3.96 MUm), with 6.60 times
      greater asymmetry in OAG eyes. The inferior quadrant showed the second greatest
      difference, with 3.91 times greater asymmetry in OAG eyes. Using a statistically
      determined cutoff of 6.0 MUm as abnormal, intereye RNFL asymmetry for global
      average achieved a sensitivity of 74.24% and specificity of 90% in
      differentiating between normal and OAG subjects, achieving a better combination
      of sensitivity and specificity than intereye RNFL asymmetry of any quadrant or
      sector. CONCLUSIONS: Intereye RNFL asymmetry may be a useful clinical OCT
      measurement to provide quantitative assessment of early glaucomatous damage.
      Newly developed algorithms for intereye RNFL asymmetry may improve the ability to
      detect glaucoma.

PMID- 24921897
TI  - Effect of insulin-induced hypoglycaemia on the peripheral nervous system: focus
      on adaptive mechanisms, pathogenesis and histopathological changes.
AB  - Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and
      type 2 diabetic patients, especially during intensive insulin therapy. The
      peripheral nervous system (PNS) depends on glucose as its primary energy source
      during normoglycaemia and, consequently, it may be particularly susceptible to
      IIH damage. Possible mechanisms for adaption of the PNS to IIH include increased
      glucose uptake, utilisation of alternative energy substrates and the use of
      Schwann cell glycogen as a local glucose reserve. However, these potential
      adaptive mechanisms become insufficient when the hypoglycaemic state exceeds a
      certain level of severity and duration, resulting in a sensory-motor neuropathy
      with associated skeletal muscle atrophy. Large myelinated motor fibres appear to
      be particularly vulnerable. Thus, although the PNS is not an obligate glucose
      consumer, as is the brain, it appears to be more prone to IIH than the central
      nervous system when hypoglycaemia is not severe (blood glucose level <= 2 mm),
      possibly reflecting a preferential protection of the brain during periods of
      inadequate glucose availability. With a primary focus on evidence from
      experimental animal studies investigating nondiabetic IIH, the present review
      discusses the effect of IIH on the PNS with a focus on adaptive mechanisms,
      pathogenesis and histological changes.

PMID- 24921898
TI  - Defining emergency department asthma visits for public health surveillance, North
      Carolina, 2008-2009.
AB  - INTRODUCTION: When using emergency department (ED) data sets for public health
      surveillance, a standard approach is needed to define visits attributable to
      asthma. Asthma can be the first (primary) or a subsequent (2nd through 11th)
      diagnosis. Our study objective was to develop a definition of ED visits
      attributable to asthma for public health surveillance. We evaluated the effect of
      including visits with an asthma diagnosis in primary-only versus subsequent
      positions. METHODS: The study was a cross-sectional analysis of population-level
      ED surveillance data. Of the 114 North Carolina EDs eligible to participate in a
      statewide surveillance system in 2008-2009, we used data from the 111 (97%) that
      participated during those years. Included were all ED visits with an ICD-9-CM
      diagnosis code for asthma in any diagnosis position (1 through 11). We formed 11
      strata based on the diagnosis position of asthma and described common chief
      complaint and primary diagnosis categories for each. Prevalence ratios compared
      each category's proportion of visits that received either asthma- or cardiac
      related procedure codes. RESULTS: Respiratory diagnoses were most common in
      records of ED visits in which asthma was the first or second diagnosis, while
      primary diagnoses of injury and heart disease were more common when asthma
      appeared in positions 3-11. Asthma-related chief complaints and procedures were
      most common when asthma was the first or second diagnosis, whereas cardiac
      procedures were more common in records with asthma in positions 3-11. CONCLUSION:
      ED visits should be defined as asthma-related when asthma is in the first or
      second diagnosis position.

PMID- 24921899
TI  - Accelerated weight gain among children during summer versus school year and
      related racial/ethnic disparities: a systematic review.
AB  - INTRODUCTION: The objective of this study was to compile and summarize research
      examining variations in weight gain among students during the summer in
      comparison to the school year, with a focus on racial/ethnic disparities and
      students who are at risk of overweight. METHODS: A systematic search of PubMed
      and Embase was conducted. Reference lists of identified articles and Google
      Scholar were also reviewed. Studies that assessed summer weight gain in school
      children were included. Inclusion criteria were: 1) a focus on children and
      adolescents aged 5 to 17 attending school; 2) a measured body composition before
      and after the summer vacation; 3) English-language articles; and 4) publication
      in a peer-reviewed journal since January 1, 1990. Data were extracted from
      selected studies in the following categories: study purpose, setting, study
      design, population, sample size, data collection method, and findings. RESULTS:
      Seven eligible studies were included in the review. Six of the 7 studies reported
      accelerated summer weight gain for at least a portion of the study population,
      with an effect of summer on weight gain identified for the following subgroups:
      black, Hispanic, and overweight children and adolescents. CONCLUSION: There may
      be a trend in increased rate of weight gain during summer school vacation,
      particularly for high-risk groups, including certain racial/ethnic populations
      and overweight children and adolescents. Potential solutions for the problem of
      accelerated summer weight gain include greater access to recreational facilities,
      physical activity programming, and summer food programs. Further research in this
      area is needed as summer weight gain may exacerbate existing health disparities.

PMID- 24921900
TI  - Strategies, actions, and outcomes of pilot state programs in public health
      genomics, 2003-2008.
AB  - State health departments in Michigan, Minnesota, Oregon, and Utah explored the
      use of genomic information, including family health history, in chronic disease
      prevention programs. To support these explorations, the Office of Public Health
      Genomics at the Centers for Disease Control and Prevention provided cooperative
      agreement funds from 2003 through 2008. The 4 states' chronic disease programs
      identified advocates, formed partnerships, and assessed public data; they
      integrated genomics into existing state plans for genetics and chronic disease
      prevention; they developed projects focused on prevention of asthma, cancer,
      cardiovascular disease, diabetes, and other chronic conditions; and they created
      educational curricula and materials for health workers, policymakers, and the
      public. Each state's program was different because of the need to adapt to
      existing culture, infrastructure, and resources, yet all were able to enhance
      their chronic disease prevention programs with the use of family health history,
      a low-tech "genomic tool." Additional states are drawing on the experience of
      these 4 states to develop their own approaches. 

PMID- 24921901
TI  - Demographic factors associated with perceptions about water safety and tap water
      consumption among adults in Santa Clara County, California, 2011.
AB  - The objective of this study was to examine differences in tap water consumption
      and perceptions of bottle versus tap water safety for Hispanics and non-Hispanic
      whites, as well as associations with other demographic characteristics. Data are
      from the Santa Clara County, California, Dietary Practices Survey (2011; N =
      306). We used logistic regression to examine associations between demographic
      characteristics and 1) perceptions that bottled water is safer than tap and 2)
      primarily consuming tap water. Hispanics were less likely than non-Hispanic
      whites to primarily drink tap water (OR = 0.33; 95% CI, 0.11-0.99), although
      there was no significant difference in perceptions that bottled water is safer
      between these groups (OR = 0.50; 95% CI, 0.11-2.27). Hispanics may be an
      important population for interventions promoting tap water consumption.

PMID- 24921902
TI  - Role of public-private partnerships in tackling the tobacco and obesity
      epidemics.
AB  - In response to the illness and death caused by preventable chronic diseases, the
      US Department of Health and Human Services created Communities Putting Prevention
      to Work to support community efforts in tackling tobacco use and obesity through
      policy, systems, and environmental change. As part of this program, 10 national
      nonprofit organizations with prevention expertise were funded and matched with
      specific community objectives. Most tobacco and obesity-related matched
      objectives were successfully accomplished by communities. Public-private
      partnerships should be considered when addressing chronic disease prevention.

PMID- 24921903
TI  - Sweet potato (Ipomoea batatas [L.] Lam)--a valuable medicinal food: a review.
AB  - Ipomoea batatas (L.) Lam, also known as sweet potato, is an extremely versatile
      and delicious vegetable that possesses high nutritional value. It is also a
      valuable medicinal plant having anti-cancer, antidiabetic, and anti-inflammatory
      activities. Sweet potato is now considered a valuable source of unique natural
      products, including some that can be used in the development of medicines against
      various diseases and in making industrial products. The overall objective of this
      review is to give a bird's-eye view of the nutritional value, health benefits,
      phytochemical composition, and medicinal properties of sweet potato.
      Specifically, this review outlines the biological activities of some of the sweet
      potato compounds that have been isolated, the pharmacological action of the sweet
      potato extract, clinical studies, and plausible medicinal applications of sweet
      potato (along with a safety evaluation), and demonstrates the potential of sweet
      potato as a medicinal food.

PMID- 24921904
TI  - Outcomes of partial nephrectomy for clinical T1b and T2 renal tumors.
AB  - PURPOSE OF REVIEW: To review current status of partial nephrectomy for treatment
      of T1b and T2 renal mass, focusing oncological and renal functional outcomes
      reported in the last 18 months, and to understand the emerging role of minimally
      invasive surgery (MIS) techniques in nephron-sparing management of T1b/T2 tumors.
      RECENT FINDINGS: With recent long-term oncological equivalence to radical
      nephrectomy and renal functional benefit, partial nephrectomy is becoming an
      alternate standard to radical nephrectomy in the management of T1b tumors. The
      role of partial nephrectomy in nonelective treatment of T2 tumors is more
      controversial; however, recent publication of two large North American series
      have added to other contemporary work that suggests oncologic equivalence and
      renal functional benefit compared to radical nephrectomy in select patients.
      Emerging data demonstrate feasibility of MIS for increasing the proportion of
      T1b/T2 tumors; however, recent trends analyses demonstrate that the majority of
      T1b/T2 partial nephrectomy are still carried out by open surgery, and concerns
      continue about prolonged ischemic times and risk of bleeding in various MIS
      settings. SUMMARY: Management of T1b and T2 renal masses is transforming with
      adoption of partial nephrectomy as a safe and feasible surgical option with
      comparable oncological and improved renal function outcomes compared to radical
      nephrectomy. MIS techniques play an expanding, though still limited, role, and
      more robust prospective data is requisite before drawing overarching conclusions.

PMID- 24921905
TI  - Variant histology: role in management and prognosis of nonmuscle invasive bladder
      cancer.
AB  - PURPOSE OF REVIEW: The true clinical significance of variant histology is
      controversial and diagnosis is challenging, especially in the setting of
      nonmuscle invasive (NMI) disease. If the presence of variant architecture in NMI
      identifies a high-risk population with a worse prognosis and better suited for
      early aggressive intervention (i.e., radical cystectomy), then treatment
      recommendations should reflect this notion. This review outlines the current
      evidence and determines whether histologic variants should change management of
      patients with nonmuscle invasive bladder cancer. RECENT FINDINGS: Patients with
      high-risk NMI tumors and variant histology should be offered early cystectomy,
      especially if harboring pure squamous, adenocarcinoma, sarcomatoid, plasmacytoid,
      or micropapillary disease. In patients with small cell disease, systemic primary
      chemotherapy is the ideal option followed by local therapy for primary tumor
      control. For squamous/glandular differentiation, nested variant, and other rare
      variants, intravesical therapy is an option based on standard risk stratification
      in patients with NMI disease. Diligence is needed in the presence of variant
      histology to minimize the risk of understaging as well as close surveillance to
      not compromise the opportunity of cure. SUMMARY: The management of nonmuscle
      invasive bladder cancer with variant histology is challenging, largely in part to
      the high risk of understaging and the background of already existing controversy
      regarding the management of high-risk NMI disease for standard urothelial cell
      carcinoma (early cystectomy vs. intravesical therapy). Future studies should be
      focused identifying if variant architecture confers different tumor biology than
      that of pure urothelial carcinoma, and if this difference translates into
      innovations in bladder sparing therapies.

PMID- 24921906
TI  - New agents for bacillus Calmette-Guerin-refractory nonmuscle invasive bladder
      cancer.
AB  - PURPOSE OF REVIEW: Radical cystectomy is the standard of care for patients who
      fail intravesical bacillus Calmette-Guerin (BCG) for nonmuscle invasive bladder
      cancer (NMIBC). For patients unwilling or unable to undergo cystectomy, numerous
      local therapies exist, although few are approved by the Food and Drug
      Administration. This review describes available therapies for this challenging
      clinical entity. RECENT FINDINGS: Combination intravesical chemotherapy, targeted
      therapy, and drug delivery enhancement have all been under recent investigation
      and are promising, although none has proven superior as of yet. SUMMARY: While
      BCG is standard treatment for intermediate and high-risk NMIBC, many patients
      fail therapy with recurrence or progression. Early cystectomy is the standard of
      care for BCG failure; however, many patients are unwilling or unable to undergo
      cystectomy. Multiple intravesical therapies have been used in this BCG failure
      population with moderate success, and, recently, technologies to improve drug
      delivery or create novel drugs have also been applied. Comparing efficacy of
      these therapies remain challenging as study cohorts are heterogeneous and study
      designs are variable. However, there are an increasing number of novel treatment
      options that can be offered to patients faced with recurrent NMIBC after BCG who
      seek bladder-sparing therapy.

PMID- 24921907
TI  - Nephron-sparing surgery for tumors in a solitary kidney.
AB  - PURPOSE OF REVIEW: Presence of a tumor in a solitary kidney is an absolute
      indication for performing nephron-sparing surgery (NSS). In the past two decades,
      new modalities for treatment of small renal mass have emerged but despite their
      evolution and promising results, partial nephrectomy remains the cornerstone of
      surgical treatment in this setting. Herein, we review the literature surrounding
      NSS in patients with a solitary kidney. RECENT FINDINGS: Data from large
      retrospective, single and multi-institutional series indicate that open partial
      nephrectomy in patients with a solitary kidney can achieve oncological control as
      well as renal function preservation with acceptable complication profile.
      Available data indicate that employing parenchymal cooling can mitigate the
      deleterious effects of prolonged clamp time during partial nephrectomy.
      Introduction of laparoscopic and, more recently, robotic approach have allowed
      minimally invasive approach in selected patients undergoing partial nephrectomy.
      Large comparative studies comparing minimally invasive approaches to open
      technique are lacking. SUMMARY: Established and emerging NSS techniques along
      with our better understating of the factors affecting function after surgery have
      fostered improvement of delivery of care in the setting of renal tumor(s) in a
      solitary kidney. Future developments should focus on minimizing the invasiveness
      of treatments while further improving cancer control and functional preservation.

PMID- 24921908
TI  - Progress made in the use of animal models for the study of high-risk, nonmuscle
      invasive bladder cancer.
AB  - PURPOSE OF REVIEW: High-risk, nonmuscle invasive bladder cancer (HR-NMIBC)
      represents a costly and difficult-to-treat disease, the molecular pathogenesis of
      which has a limited understanding. Most preclinical models for the study of
      bladder cancer are more appropriate for the study of advanced disease. However,
      recent key advances in preclinical animal models places us at an opportune
      position to better understand HR-NMIBC. RECENT FINDINGS: Discoveries in the basic
      sciences allow us to better understand tumor biology when building models of
      bladder cancer. Of note, a key study on urothelial progenitor cells recently
      highlighted an important role for Sonic hedgehog-positive cells and retinoid
      signaling that is essential for urothelial development and regeneration. In the
      translational realm, transgenic mouse models continue to be used, with a recent
      interest in the role of Wnt/beta-catenin in urothelial carcinomas. Tissue
      recombination models are also being increasingly utilized to better recreate the
      tissue microenvironment and better understand stromal-epithelial interactions and
      the impact of genetic alterations on tissue differentiation. Lastly, the avatar
      mouse systems, which involve direct xenotransplantation of human tumor specimens
      into immunocompromised mice, represent an additional approach to study cancer
      characteristics in a preserved tissue context. SUMMARY: With molecular
      alterations remaining an unclear area of our understanding of HR-NMIBC,
      preclinical models of bladder cancer serve as essential tools to discover
      specific genetic compromises in disease pathogenesis and the therapeutics to
      treat them.

PMID- 24921909
TI  - The association of diabetes and anti-diabetic medications with clinical outcomes
      in multiple myeloma.
AB  - BACKGROUND: Insulin/insulin-like growth factor-1 signalling may underlie the
      promoting effect of type 2 diabetes on cancer. This study examined the
      association of diabetes, including steroid-induced diabetes (SID), and the impact
      of anti-diabetic medication on clinical outcomes of multiple myeloma (MM).
      METHODS: A retrospective review was conducted of 1240 MM patients. Overall
      survival (OS) and MM disease status prior to death were analysed. RESULTS:
      Diabetic patients had a significantly shorter OS than non-diabetic patients
      (median: 65.4 vs 98.7 months). In multivariate analysis, SID was a significant
      predictor of decreased OS, along with age, comorbidity, MM stage, and cytogenetic
      abnormalities. Analyzing only the diabetic MM patients, Cox regression showed
      that metformin predicted an increased OS, whereas use of insulin/analogues
      predicted a decreased OS. Competing risk analysis showed that DM was associated
      with increased cumulative incidence of death with progressive MM. Among the
      diabetics, multivariate regression showed that insulin/analogues were associated
      with increased, but metformin with decreased death with progressive MM. Potential
      immortal time bias was evaluated by landmark analyses. CONCLUSIONS: DM, SID in
      particular, is associated with poor clinical outcomes in MM. Insulin/analogues
      are associated with poor outcomes, whereas metformin is associated with improved
      outcomes. No conclusion about causal relationships can be made at this time.
      Managing hyperglycaemia with non-insulin regimens should be investigated in
      randomised trials.

PMID- 24921910
TI  - Identifying patients at risk of emergency admission for colorectal cancer.
AB  - BACKGROUND: Patients whose colorectal cancer is treated after an emergency
      admission tend to have late-stage cancer and a poor prognosis. We identified risk
      factors for an emergency admission by linking data from the National Bowel Cancer
      Audit (NBCA) and the English Hospital Episode Statistics (HES), an administrative
      database of all admissions to English National Health Service hospitals, which
      includes data on mode of admission. METHODS: We identified all adults included in
      the NBCA with a primary diagnosis of bowel cancer, excluding cancer of the
      appendix, between August 2007 and July 2011 whose record could be linked to HES.
      Multivariable logistic regression was used to estimate adjusted odds ratios (OR)
      for an emergency admission for colorectal cancer. All risk factors were adjusted
      for cancer site and calendar year. RESULTS: 97,909 adults were identified with a
      primary diagnosis of bowel cancer and 82,777 patients could be linked to HES.
      Patients who were older, female, of a non-white ethnic background, and more
      socioeconomically deprived, and those with dementia or cardiac, neurologic and
      liver disease had an increased risk of presenting as an emergency admission. The
      strongest risk factors were age (90 compared with 70 years: OR 2.99, 95% CI 2.84
      to 3.15), dementia (OR 2.46, 2.18 to 2.79), and liver disease (OR 1.87, 1.69 to
      2.08). CONCLUSIONS: Our study identifies risk factors that may impair health
      seeking behaviour and access to healthcare. An earlier recognition of symptoms in
      patients with these risk factors may contribute to better outcomes.

PMID- 24921911
TI  - Treatment preferences and involvement in treatment decision making of patients
      with endometrial cancer and clinicians.
AB  - BACKGROUND: Vaginal brachytherapy (VBT) in high-intermediate-risk endometrial
      cancer (EC) provides a significant reduction in the risk of local cancer
      recurrence, but without survival benefit and with increased mucosal atrophy. Five
      year local control is estimated to be similar for VBT and a watchful waiting
      policy (WWP), in which patients receive VBT combined with external radiation in
      case of a recurrence. Our aim was to assess treatment preferences of EC patients
      and clinicians regarding VBT and WWP, and to evaluate their preferred and
      perceived involvement in treatment decision making. METHODS: Interviews were held
      with 95 treated EC patients. The treatment trade-off method was used to assess
      the minimally desired benefit from VBT in local control. Patients' preferred and
      perceived involvement in decision making were assessed using a questionnaire.
      Seventy-seven clinicians completed a questionnaire assessing their minimally
      desired benefit and preferred involvement in decision making. RESULTS: Minimally
      desired benefit of VBT was significantly lower for patients than for clinicians
      (median=0 vs 8%, P<0.001), for irradiated than for non-irradiated patients
      (median=0 vs 6.5%, P<0.001), and for radiation oncologists than for
      gynaecologists (median=4 vs 13%, P<0.001). Substantial variation existed within
      the groups of patients and clinicians. Participants preferred the patient and
      clinician to share in the decision about VBT. However, irradiated patients
      indicated low perceived involvement in actual treatment decision making.
      CONCLUSIONS: We found variations between and within patients and clinicians in
      minimally desired benefit from VBT. However, the recurrence risk at which
      patients preferred VBT was low. Our results showed that patients consider active
      participation in decision making essential.

PMID- 24921912
TI  - Surgery combined with controlled-release doxorubicin silk films as a treatment
      strategy in an orthotopic neuroblastoma mouse model.
AB  - BACKGROUND: Neuroblastoma tumour resection goal is maximal tumour removal. We
      hypothesise that combining surgery with sustained, local doxorubicin application
      can control tumour growth. METHODS: We injected human neuroblastoma cells into
      immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was
      >300 mm(3), 80-90% of tumour was resected and treated as follows: instantaneous
      release silk film with 100 MUg doxorubicin (100IR), controlled-release film with
      200 MUg (200CR) over residual tumour bed; and 100 and 200 MUg intravenous
      doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed.
      RESULTS: Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells.
      Tumours reached 1800+/-180 mm(3) after 28 days, 2200+/-290 mm(3) after 35 days,
      1280+/-260 mm(3) after 63 days, and 1700+/-360 mm(3) after 84 days, respectively.
      At 3 days post KELLY tumour resection, tumour volumes were similar across all
      groups (P=0.6210). Tumour growth rate was similar in untreated vs control film,
      100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs
      200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all
      doxorubicin groups was slower than that of control (P: <0.0001-0.0069). At the
      interface of the 200CR film and tumour, there was cellular necrosis, surrounded
      by apoptotic cells before reaching viable tumour cells. CONCLUSIONS: Combining
      surgical resection and sustained local doxorubicin treatment is effective in
      tumour control. Administering doxorubicin in a local, controlled manner is
      superior to giving an equivalent intravenous dose in tumour control.

PMID- 24921913
TI  - Prognostic significance of CD44 variant 2 upregulation in colorectal cancer.
AB  - BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in
      colorectal cancer (CRC). However, their clinical significance is currently
      unclear. Here, we evaluated primary CRC cell isolates to determine the
      significance of several CSC markers, including CD133 and CD44, as predictors of
      tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh
      clinical samples of 77 CRCs were selected by flow cytometric sorting and
      evaluated for tumourigenicity following subcutaneous transplantation into
      NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts
      and a complementary DNA library compiled from 167 CRC patient samples. RESULTS:
      CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more
      tumourigenic than the total cell population. The clinical samples expressed
      several transcript variants of CD44. Variant 2 was specifically overexpressed in
      both primary tumours and xenografts in comparison with the normal mucosa. A
      prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year
      survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than
      the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC
      marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2
      have a poorer prognosis than patients with other CD44 variants.

PMID- 24921914
TI  - MiR-224 promotes the chemoresistance of human lung adenocarcinoma cells to
      cisplatin via regulating G1/S transition and apoptosis by targeting
      p21(WAF1/CIP1).
AB  - BACKGROUND: Increasing evidence has shown that microRNAs (miRNAs) can serve as
      oncogenes and tumour suppressors to participate in tumour development. However,
      the roles of miRNAs in chemoresistance of human lung adenocarcinoma (LA) remain
      largely undefined. METHODS: On the basis of miRNA microarray data, miR-224 was
      identified as the most upregulated miRNA in cisplatin (DDP; cis
      diamminedichloroplatinum II)-resistant A549 cells compared with parental A549
      cells. The aim of our study was to investigate the roles of miR-224 in the
      formation of DDP-resistant phenotype of LA cells and its possible molecular
      mechanisms. RESULTS: Here we showed that miR-224 could promote the in vitro and
      in vivo DDP resistance of LA cells via regulating G1/S cell cycle transition and
      apoptosis. p21(WAF1/CIP1), a potent cyclin-dependent kinase inhibitor, was
      identified as the direct and functional target gene of miR-224. Overexpression of
      p21(WAF1/CIP1) could phenocopy the effect of miR-224 downregulation and silencing
      of p21(WAF1/CIP1) could partially reverse the effect of miR-224 downregulation on
      DDP resistance of DDP-resistant LA cells. In addition, miR-224 could affect the
      G1/S transition of cell cycle and apoptosis in LA cells through the
      p21(WAF1/CIP1)-pRb pathway and the intrinsic mitochondrial death pathway.
      Furthermore, miR-224 was found to be downregulated in DDP-responding LA tissues,
      and its expression was inversely correlated with p21(WAF1/CIP1). Multivariate
      analyses indicated that the status of miR-224 might be an independent prognostic
      factor for predicting the survival of LA patients. CONCLUSIONS: Our findings shed
      novel light on the roles of miR-224/p21(WAF1/CIP1) signalling in the DDP
      resistance of LA cells, and targeting it will be a potential strategic approach
      for reversing the DDP resistance in human LAs.

PMID- 24921915
TI  - Elevated expression of myosin X in tumours contributes to breast cancer
      aggressiveness and metastasis.
AB  - BACKGROUND: Myosin X (MYO10) was recently reported to promote tumour invasion by
      transporting integrins to filopodial tips in breast cancer. However, the role of
      MYO10 in tumours remains poorly defined. Here, we report that MYO10 is required
      in invadopodia to mediate invasive growth and extracellular matrix degradation,
      which depends on the binding of MYO10's pleckstrin homology domain to
      PtdIns(3,4,5)P3. METHODS: The expression of MYO10 and its associations with
      clinicopathological and biological factors were examined in breast cancer cells
      and breast cancer specimens (n=120). Cell migration and invasion were
      investigated after the silencing of MYO10. The ability of cells to form
      invadopodia was studied using a fluorescein isothiocyanate-conjugated gelatin
      degradation assay. A mouse model was established to study tumour invasive growth
      and metastasis in vivo. RESULTS: Elevated MYO10 levels were correlated with
      oestrogen receptor status, progesterone receptor status, poor differentiation,
      and lymph node metastasis. Silencing MYO10 reduced cell migration and invasion.
      Invadopodia were responsible for MYO10's role in promoting invasion. Furthermore,
      decreased invasive growth and lung metastasis were observed in the MYO10-silenced
      nude mouse model. CONCLUSIONS: Our findings suggest that elevated MYO10
      expression increases the aggressiveness of breast cancer; this effect is
      dependent on the involvement of MYO10 in invadopodial formation.

PMID- 24921916
TI  - The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with
      small-cell lung cancer.
AB  - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte
      ratio (PLR) are prognostic factors for various types of cancer. In this study, we
      assessed the association of NLR and PLR with the prognosis of small-cell lung
      cancer (SCLC) in patients who received the standard treatment. METHODS: We
      retrospectively reviewed patients who were diagnosed with SCLC and treated with
      platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang
      National University Hospital Regional Cancer Center and Changwon Samsung
      Hospital. RESULTS: In total, 187 patients were evaluated. Compared with low NLR
      (<4), high NLR (?4) at diagnosis was associated with poor performance status,
      advanced stage, and lower response rate. Median overall survival (OS) and
      progression-free survival (PFS) were worse in the high-NLR group (high vs low,
      11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In
      contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and
      P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase,
      and NLR at diagnosis were independent prognostic factors for OS and PFS.
      CONCLUSIONS: NLR is easily measurable and reflects the SCLC prognosis. A future
      prospective study is warranted to confirm our results.

PMID- 24921917
TI  - The expression of platelet-activating factor receptor modulates the cisplatin
      sensitivity of ovarian cancer cells: a novel target for combination therapy.
AB  - BACKGROUND: Ovarian cancer has the highest mortality rate of the gynaecological
      cancers. Although cisplatin (CDDP) is an effective treatment for ovarian cancer,
      recurrence is frequent and leads to death. The objective was to explore the role
      and possible mechanisms of platelet-activating factor receptor (PAFR) signalling
      in CDDP-treated ovarian cancer cells. METHODS: The upregulation of PAFR in CDDP
      treated ovarian cancer cells was observed using realtime PCR and Western blot.
      The potential role of PAFR in modulating the CDDP sensitivity was assessed using
      a pharmacological inhibitor and siRNA knockdown. The PAFR-activated signalling
      pathways involved in cell responses to CDDP were assessed. RESULTS: Cisplatin
      induced increased PAFR expression in two ovarian cancer cell lines. The
      upregulation of PAFR by CDDP correlated with the time-dependent accumulation of
      NF-kappaB and HIF-1alpha in the nucleus. The inhibition of PAFR sensitised the
      ovarian cancer cells to CDDP. The PI3K and ERK pathways lie downstream of
      activated PAFR in CDDP-treated cells and their inhibition enhanced CDDP
      sensitivity. Finally, co-treatment with a PAFR antagonist (Ginkgolide B) and CDDP
      markedly reduced tumour growth in an in vivo model of ovarian cancer.
      CONCLUSIONS: Together, these findings suggest that PAFR is a novel and promising
      therapeutic target for sensitising ovarian cancer cells to CDDP.

PMID- 24921918
TI  - Possible pro-carcinogenic association of endotoxin on lung cancer among Shanghai
      women textile workers.
AB  - BACKGROUND: Endotoxin (lipopolysaccharide) is a widespread contaminant in many
      environmental settings. Since the 1970s, there has been generally consistent
      evidence indicating reduced risks for lung cancer associated with occupational
      endotoxin exposure. METHODS: We updated a case-cohort study nested within a
      cohort of 267,400 female textile workers in Shanghai, China. We compared exposure
      histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with
      those of a reference subcohort of 3022 workers who were free of lung cancer at
      the end of follow-up. We applied Cox proportional hazards modelling to estimate
      exposure-response trends, adjusted for age and smoking, for cumulative exposures
      lagged by 0, 10, and 20 years, and separately for time windows of ?15 and >15
      years since first exposure. RESULTS: We observed no associations between
      cumulative exposure and lung cancer, irrespective of lag interval. In contrast,
      analyses by exposure time windows revealed modestly elevated, but not
      statistically significant relative risks (~1.27) at the highest three exposure
      quintiles for exposures that occurred >15 years since first exposure.
      CONCLUSIONS: The findings do not support a protective effect of endotoxin, but
      are suggestive of possible lung cancer promotion with increasing time since first
      exposure.

PMID- 24921919
TI  - Feasibility RCT of definitive chemoradiotherapy or chemotherapy and surgery for
      oesophageal squamous cell cancer.
AB  - BACKGROUND: The optimal treatment for localised oesophageal squamous cell
      carcinoma (SCC) is uncertain. We assessed the feasibility of an RCT comparing
      neoadjuvant treatment and surgery with definitive chemoradiotherapy. METHODS: A
      feasibility RCT in three centres examined incident patients and reasons for
      ineligibility using multi-disciplinary team meeting records. Eligible patients
      were offered participation in the RCT with integrated qualitative research
      involving audio-recorded recruitment appointments and interviews with patients to
      inform recruitment training for staff. RESULTS: Of 375 patients with oesophageal
      SCC, 42 (11.2%) were eligible. Reasons for eligibility varied between centres,
      with significantly differing proportions of patients excluded because of total
      tumour length (P=0.002). Analyses of audio-recordings and patient interviews
      showed that recruiters had challenges articulating the trial design in simple
      terms, balancing treatment arms and explaining the need for randomisation. Before
      analyses of the qualitative data and recruiter training no patients were
      randomised. Following training in one centre 5 of 16 eligible patients were
      randomised. CONCLUSIONS: An RCT of surgical vs non-surgical treatment for SCC of
      the oesophagus is not feasible in the UK alone because of the low number of
      incident eligible patients. A trial comparing diverse treatment approaches may be
      possible with investment to support the recruitment process.

PMID- 24921920
TI  - Structurally diverse MDM2-p53 antagonists act as modulators of MDR-1 function in
      neuroblastoma.
AB  - BACKGROUND: A frequent mechanism of acquired multidrug resistance in human
      cancers is overexpression of ATP-binding cassette transporters such as the Multi
      Drug Resistance Protein 1 (MDR-1). Nutlin-3, an MDM2-p53 antagonist, has
      previously been reported to be a competitive MDR-1 inhibitor. METHODS: This study
      assessed whether the structurally diverse MDM2-p53 antagonists, MI-63, NDD0005,
      and RG7388 are also able to modulate MDR-1 function, particularly in p53 mutant
      neuroblastoma cells, using XTT-based cell viability assays, western blotting, and
      liquid chromatography-mass spectrometry analysis. RESULTS: Verapamil and the MDM2
      p53 antagonists potentiated vincristine-mediated growth inhibition in a
      concentration-dependent manner when used in combination with high MDR-1
      expressing p53 mutant neuroblastoma cell lines at concentrations that did not
      affect the viability of cells when given alone. Liquid chromatography-mass
      spectrometry analyses showed that verapamil, Nutlin-3, MI-63 and NDD0005, but not
      RG7388, led to increased intracellular levels of vincristine in high MDR-1
      expressing cell lines. CONCLUSIONS: These results show that in addition to Nutlin
      3, other structurally unrelated MDM2-p53 antagonists can also act as MDR-1
      inhibitors and reverse MDR-1-mediated multidrug resistance in neuroblastoma cell
      lines in a p53-independent manner. These findings are important for future
      clinical trial design with MDM2-p53 antagonists when used in combination with
      agents that are MDR-1 substrates.

PMID- 24921921
TI  - Population-based comparison of prognostic factors in invasive micropapillary and
      invasive ductal carcinoma of the breast.
AB  - BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a variant of breast
      carcinoma with a higher propensity for lymph node metastases compared with
      invasive ductal carcinoma (IDC). METHODS: Retrospective analysis of 636 IMPC and
      297 735 IDC cases in the Surveillance, Epidemiology and End RESULTS database
      comparing disease-specific survival (DSS) and overall survival (OS) between IMPC
      and IDC. RESULTS: A higher percentage of IMPC cases (52.0%) had nodal metastases
      compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and
      82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both
      IMPC and IDC, oestrogen-receptor positivity was associated with better survival,
      while having four or more positive lymph nodes or larger tumour size correlated
      with worse survival. Radiotherapy provided a survival benefit for both
      histological types. CONCLUSIONS: Despite IMPC's higher propensity for lymph node
      metastasis, IMPC has DSS and OS that compare favourably with IDC.

PMID- 24921922
TI  - Off-pump compared to minimal extracorporeal circulation surgery in coronary
      artery bypass grafting.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) using extracorporeal
      circulation (ECC) is still the gold standard. However, alternative techniques
      have been developed to avoid ECC and its potential adverse effects. These
      encompass minimal extracorporeal circulation (MECC) or off-pump coronary artery
      bypass grafting (OPCAB). However, the prevailing potential benefits when
      comparing MECC and OPCABG are not yet clearly established. METHODS: In this
      retrospective study we investigated the potential benefits of MECC and OPCABG in
      697 patients undergoing CABG. Of these, 555 patients had been operated with MECC
      and 142 off-pump. The primary endpoint was Troponin T level as an indicator for
      myocardial damage. RESULTS: Study groups were not significantly different in
      general. However, patients undergoing OPCABG were significantly older (65.01
      years +/- 9.5 vs. 69.39 years +/- 9.5; p value <0.001) with a higher Logistic
      EuroSCORE I (4.92% +/- 6.5 vs. 5.88% +/- 6.8; p value = 0.017). Operating off
      pump significantly reduced the need for intra-operative blood products (0.7% vs.
      8.6%; p-value <0.001) and the length of stay in the intensive care unit (ICU)
      (2.04 days +/- 2.63 vs. 2.76 days +/- 2.79; p value <0.001). Regarding other
      blood values a significant difference could not be found in the adjusted
      calculations. The combined secondary endpoint, major cardiac or cerebrovascular
      events (MACCE), was equal in both groups as well. CONCLUSIONS: Coronary artery
      bypass grafting using MECC or OPCABG are two comparable techniques with
      advantages for OPCABG regarding the reduced need for intra-operative blood
      products and shorter length of stay in the ICU. However serological values and
      combined endpoint MACCE did not differ significantly in both groups.

PMID- 24921923
TI  - Spatial Transmission of 2009 Pandemic Influenza in the US.
AB  - The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed
      examination of the spatial dynamics of an emerging pathogen. In the US, the
      pandemic was characterized by substantial geographical heterogeneity: the 2009
      spring wave was limited mainly to northeastern cities while the larger fall wave
      affected the whole country. Here we use finely resolved spatial and temporal
      influenza disease data based on electronic medical claims to explore the spread
      of the fall pandemic wave across 271 US cities and associated suburban areas. We
      document a clear spatial pattern in the timing of onset of the fall wave,
      starting in southeastern cities and spreading outwards over a period of three
      months. We use mechanistic models to tease apart the external factors associated
      with the timing of the fall wave arrival: differential seeding events linked to
      demographic factors, school opening dates, absolute humidity, prior immunity from
      the spring wave, spatial diffusion, and their interactions. Although the onset of
      the fall wave was correlated with school openings as previously reported, models
      including spatial spread alone resulted in better fit. The best model had a
      combination of the two. Absolute humidity or prior exposure during the spring
      wave did not improve the fit and population size only played a weak role. In
      conclusion, the protracted spread of pandemic influenza in fall 2009 in the US
      was dominated by short-distance spatial spread partially catalysed by school
      openings rather than long-distance transmission events. This is in contrast to
      the rapid hierarchical transmission patterns previously described for seasonal
      influenza. The findings underline the critical role that school-age children play
      in facilitating the geographic spread of pandemic influenza and highlight the
      need for further information on the movement and mixing patterns of this age
      group. 

PMID- 24921924
TI  - The role of platelets in the pathogenesis of viral hemorrhagic fevers.
AB  - Viral hemorrhagic fevers (VHF) are acute zoonotic diseases that, early on, seem
      to cause platelet destruction or dysfunction. Here we present the four major ways
      viruses affect platelet development and function and new evidence of molecular
      factors that are preferentially induced by the more pathogenic members of the
      families Flaviviridae, Bunyaviridae, Arenaviridae, and Filoviridae. A systematic
      search was performed through the main medical electronic databases using as
      parameters all current findings concerning platelets in VHF. Additionally, the
      review contains information from conference proceedings. 

PMID- 24921925
TI  - Potential role of Flavobacterial gliding-motility and type IX secretion system
      complex in root colonization and plant defense.
AB  - Members of the Flavobacterium genus are often highly abundant in the rhizosphere.
      Nevertheless, the physiological characteristics associated with their enhanced
      rhizosphere competence are currently an enigma. Flavobacteria possess a unique
      gliding-motility complex that is tightly associated with a recently characterized
      Bacteroidetes-specific type IX protein secretion system, which distinguishes them
      from the rest of the rhizosphere microbiome. We hypothesize that proper
      functionality of this complex may confer a competitive advantage in the
      rhizosphere. To test this hypothesis, we constructed mutant and complement root
      associated flavobacterial variants with dysfunctional secretion and gliding
      motility, and tested them in a series of in planta experiments. These mutants
      demonstrated significantly lower rhizosphere persistence (approximately 10-fold),
      plant root colonization (approximately fivefold), and seed adhesion capacity
      (approximately sevenfold) than the wild-type strains. Furthermore, the biocontrol
      capacity of the mutant strain toward foliar-applied Clavibacter michiganensis was
      significantly impaired relative to the wild-type strain, suggesting a role of the
      gliding and secretion complex in plant protection. Collectively, these results
      provide an initial link between the high abundance of flavobacteria in the
      rhizosphere and their unique physiology, indicating that the flavobacterial
      gliding-motility and secretion complex may play a central role in root
      colonization and plant defense. 

PMID- 24921929
TI  - Electric field structures in thin films: formation and properties.
AB  - A newly discovered class of molecular materials, so-called "spontelectrics",
      display spontaneous electric fields. Here we show that the novel properties of
      spontelectrics can be used to create composite spontelectrics, illustrating how
      electric fields in solid films may be structured on the nanoscale by combining
      layers of different spontelectric materials. This is demonstrated using the
      spontelectric materials nitrous oxide, toluene, isoprene, isopentane, and CF2Cl2.
      These yield a variety of tailored electric field structures, with individual
      layers harboring fields between 10(7) and 10(8) V/m. Fields may be of the same
      sign or of opposite sign, the latter enabling the creation of nanoscale potential
      wells. The formation of fields is followed using an established electron beam
      technique, employing the ASTRID synchrotron storage ring. The influence of
      temperature on heterolayer structures, displaying new Curie effects, and the
      nature of the interfacial region between different spontelectrics are also
      discussed. 

PMID- 24921928
TI  - Early embryogenesis-specific expression of the rice transposon Ping enhances
      amplification of the MITE mPing.
AB  - Miniature inverted-repeat transposable elements (MITEs) are numerically
      predominant transposable elements in the rice genome, and their activities have
      influenced the evolution of genes. Very little is known about how MITEs can
      rapidly amplify to thousands in the genome. The rice MITE mPing is quiescent in
      most cultivars under natural growth conditions, although it is activated by
      various stresses, such as tissue culture, gamma-ray irradiation, and high
      hydrostatic pressure. Exceptionally in the temperate japonica rice strain EG4
      (cultivar Gimbozu), mPing has reached over 1000 copies in the genome, and is
      amplifying owing to its active transposition even under natural growth
      conditions. Being the only active MITE, mPing in EG4 is an appropriate material
      to study how MITEs amplify in the genome. Here, we provide important findings
      regarding the transposition and amplification of mPing in EG4. Transposon display
      of mPing using various tissues of a single EG4 plant revealed that most de novo
      mPing insertions arise in embryogenesis during the period from 3 to 5 days after
      pollination (DAP), and a large majority of these insertions are transmissible to
      the next generation. Locus-specific PCR showed that mPing excisions and
      insertions arose at the same time (3 to 5 DAP). Moreover, expression analysis and
      in situ hybridization analysis revealed that Ping, an autonomous partner for
      mPing, was markedly up-regulated in the 3 DAP embryo of EG4, whereas such up
      regulation of Ping was not observed in the mPing-inactive cultivar Nipponbare.
      These results demonstrate that the early embryogenesis-specific expression of
      Ping is responsible for the successful amplification of mPing in EG4. This study
      helps not only to elucidate the whole mechanism of mPing amplification but also
      to further understand the contribution of MITEs to genome evolution. 

PMID- 24921927
TI  - Protein kinase C and extracellular signal-regulated kinase regulate movement,
      attachment, pairing and egg release in Schistosoma mansoni.
AB  - Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are
      evolutionary conserved cell signalling enzymes that coordinate cell function.
      Here we have employed biochemical approaches using 'smart' antibodies and
      functional screening to unravel the importance of these enzymes to Schistosoma
      mansoni physiology. Various PKC and ERK isotypes were detected, and were
      differentially phosphorylated (activated) throughout the various S. mansoni life
      stages, suggesting isotype-specific roles and differences in signalling
      complexity during parasite development. Functional kinase mapping in adult worms
      revealed that activated PKC and ERK were particularly associated with the adult
      male tegument, musculature and oesophagus and occasionally with the oesophageal
      gland; other structures possessing detectable activated PKC and/or ERK included
      the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and
      excretory ducts. Pharmacological modulation of PKC and ERK activity in adult
      worms using GF109203X, U0126, or PMA, resulted in significant physiological
      disturbance commensurate with these proteins occupying a central position in
      signalling pathways associated with schistosome muscular activity, neuromuscular
      coordination, reproductive function, attachment and pairing. Increased activation
      of ERK and PKC was also detected in worms following praziquantel treatment, with
      increased signalling associated with the tegument and excretory system and
      activated ERK localizing to previously unseen structures, including the cephalic
      ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis,
      and identify these kinase groups as potential targets for chemotherapeutic
      treatments against human schistosomiasis, a neglected tropical disease of
      enormous public health significance. 

PMID- 24921926
TI  - The microbiota-gut-brain axis in functional gastrointestinal disorders.
AB  - Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a
      significant burden on health care and society, and impact patients' quality of
      life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying
      pathophysiology. They are considered to result from the interaction of altered
      gut physiology and psychological factors via the gut-brain axis, where brain and
      gut symptoms are reciprocally influencing each other's expression. Intestinal
      microbiota, as a part of the gut-brain axis, plays a central role in FGIDs.
      Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered
      composition of the gut microbiota compared with healthy controls and benefit, at
      the gastrointestinal and psychological levels, from the use of probiotics and
      antibiotics. This review aims to recapitulate the available literature on FGIDs
      and microbiota-gut-brain axis. 

PMID- 24921931
TI  - sigma(ECF) factors of gram-positive bacteria: a focus on Bacillus subtilis and
      the CMNR group.
AB  - The survival of bacteria to different environmental conditions depends on the
      activation of adaptive mechanisms, which are intricately driven through gene
      regulation. Because transcriptional initiation is considered to be the major step
      in the control of bacterial genes, we discuss the characteristics and roles of
      the sigma factors, addressing (1) their structural, functional and phylogenetic
      classification; (2) how their activity is regulated; and (3) the promoters
      recognized by these factors. Finally, we focus on a specific group of alternative
      sigma factors, the so-called sigma(ECF) factors, in Bacillus subtilis and some of
      the main species that comprise the CMNR group, providing information on the roles
      they play in the microorganisms' physiology and indicating some of the genes
      whose transcription they regulate. 

PMID- 24921932
TI  - Pharmacokinetics of anti-HBV polyoxometalate in rats.
AB  - Polyoxometalates are non-nucleoside analogs that have been proven to exhibit
      broad-spectrum antiviral activity. In particular, Cs2K4Na[SiW9Nb3O40].H2O 1 shows
      low toxicity and high activity against HBV. The preclinical pharmacokinetics of
      Compound 1 in rats were characterized by establishing and applying inductively
      coupled plasma-mass spectrometry method to determine the concentration of W in
      plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method
      demonstrated good sensitivity and application in the pharmacokinetics study of
      polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or
      oral administration fit a two-compartment model. Tmax ranges from 0.1 h to 3 h
      and the T1/2 of Compound 1 is between 20 h and 30 h. The absolute bioavailability
      of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%,
      respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36
      mg/ml of Compound 1 are 62.13+/-9.41%, 71.20+/-24.98% and 49.00+/-25.59%,
      respectively. Compound 1 was widely distributed throughout the body, and high
      levels of compound 1 were found in the kidney and liver. The level of Compound 1
      in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile,
      respectively. For elaborate pharmacokinetic characteristics to be fully
      understood, the metabolism of Compound 1 needs to be studied further. 

PMID- 24921930
TI  - Vitamin D induces increased systolic arterial pressure via vascular reactivity
      and mechanical properties.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate whether supplementation of
      high doses of cholecalciferol for two months in normotensive rats results in
      increased systolic arterial pressure and which are the mechanisms involved.
      Specifically, this study assesses the potential effect on cardiac output as well
      as the changes in aortic structure and functional properties. METHODS: Male
      Wistar rats were divided into three groups: 1) Control group (C, n = 20), with no
      supplementation of vitamin D, 2) VD3 (n = 19), supplemented with 3,000 IU vitamin
      D/kg of chow; 3) VD10 (n = 21), supplemented with 10,000 IU vitamin D/kg of chow.
      After two months, echocardiographic analyses, measurements of systolic arterial
      pressure (SAP), vascular reactivity, reactive oxygen species (ROS) generation,
      mechanical properties, histological analysis and metalloproteinase-2 and -9
      activity were performed. RESULTS: SAP was higher in VD3 and VD10 than in C rats
      (p = 0.001). Echocardiographic variables were not different among groups.
      Responses to phenylephrine in endothelium-denuded aortas was higher in VD3
      compared to the C group (p = 0.041). Vascular relaxation induced by acetylcholine
      (p = 0.023) and sodium nitroprusside (p = 0.005) was impaired in both
      supplemented groups compared to the C group and apocynin treatment reversed
      impaired vasodilation. Collagen volume fraction (<0.001) and MMP-2 activity (p =
      0.025) was higher in VD10 group compared to the VD3 group. Elastin volume
      fraction was lower in VD10 than in C and yield point was lower in VD3 than in C.
      CONCLUSION: Our findings support the view that vitamin D supplementation
      increases arterial pressure in normotensive rats and this is associated with
      structural and functional vascular changes, modulated by NADPH oxidase, nitric
      oxide, and extracellular matrix components.

PMID- 24921933
TI  - A computational model of the fetal circulation to quantify blood redistribution
      in intrauterine growth restriction.
AB  - Intrauterine growth restriction (IUGR) due to placental insufficiency is
      associated with blood flow redistribution in order to maintain delivery of
      oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI)
      is a key arterial connection between the cerebral and placental circulations,
      quantifying AoI blood flow has been proposed to assess this brain sparing effect
      in clinical practice. While numerous clinical studies have studied this
      parameter, fundamental understanding of its determinant factors and its
      quantitative relation with other aspects of haemodynamic remodeling has been
      limited. Computational models of the cardiovascular circulation have been
      proposed for exactly this purpose since they allow both for studying the
      contributions from isolated parameters as well as estimating properties that
      cannot be directly assessed from clinical measurements. Therefore, a
      computational model of the fetal circulation was developed, including the key
      elements related to fetal blood redistribution and using measured cardiac outflow
      profiles to allow personalization. The model was first calibrated using patient
      specific Doppler data from a healthy fetus. Next, in order to understand the
      contributions of the main parameters determining blood redistribution, AoI and
      middle cerebral artery (MCA) flow changes were studied by variation of cerebral
      and peripheral-placental resistances. Finally, to study how this affects an
      individual fetus, the model was fitted to three IUGR cases with different degrees
      of severity. In conclusion, the proposed computational model provides a good
      approximation to assess blood flow changes in the fetal circulation. The results
      support that while MCA flow is mainly determined by a fall in brain resistance,
      the AoI is influenced by a balance between increased peripheral-placental and
      decreased cerebral resistances. Personalizing the model allows for quantifying
      the balance between cerebral and peripheral-placental remodeling, thus providing
      potentially novel information to aid clinical follow up. 

PMID- 24921935
TI  - Practical and convenient synthesis of 1,6-di- or 1,2,5,6-tetra-arylhexa-1,3,5
      trienes by the dimerization of Pd(0)-complexed alkenylcarbenes generated from pi
      allylpalladium intermediates.
AB  - Pd(0)-complexed 3-aryl or 2,3-diaryl propenylcarbenes generated from alpha-silyl
      , alpha-germyl-, or alpha-boryl-sigma-allylpalladium intermediates undergo self
      dimerization to provide 1,6-di- or 1,2,5,6-tetraarylhexa-1,3,5-trienes in good to
      high yields. This method allows the use of a pi-allylpalladium intermediate for a
      carbenoid precursor. Furthermore, the obtained 1,2,5,6-tetraarylhexa-1,3,5
      trienes exhibit aggregation-induced emission enhancement property. 

PMID- 24921934
TI  - Contribution of auditory working memory to speech understanding in mandarin
      speaking cochlear implant users.
AB  - PURPOSE: To investigate how auditory working memory relates to speech perception
      performance by Mandarin-speaking cochlear implant (CI) users. METHOD: Auditory
      working memory and speech perception was measured in Mandarin-speaking CI and
      normal-hearing (NH) participants. Working memory capacity was measured using
      forward digit span and backward digit span; working memory efficiency was
      measured using articulation rate. Speech perception was assessed with: (a) word
      in-sentence recognition in quiet, (b) word-in-sentence recognition in speech
      shaped steady noise at +5 dB signal-to-noise ratio, (c) Chinese disyllable
      recognition in quiet, (d) Chinese lexical tone recognition in quiet. Self
      reported school rank was also collected regarding performance in schoolwork.
      RESULTS: There was large inter-subject variability in auditory working memory and
      speech performance for CI participants. Working memory and speech performance
      were significantly poorer for CI than for NH participants. All three working
      memory measures were strongly correlated with each other for both CI and NH
      participants. Partial correlation analyses were performed on the CI data while
      controlling for demographic variables. Working memory efficiency was
      significantly correlated only with sentence recognition in quiet when working
      memory capacity was partialled out. Working memory capacity was correlated with
      disyllable recognition and school rank when efficiency was partialled out. There
      was no correlation between working memory and lexical tone recognition in the
      present CI participants. CONCLUSIONS: Mandarin-speaking CI users experience
      significant deficits in auditory working memory and speech performance compared
      with NH listeners. The present data suggest that auditory working memory may
      contribute to CI users' difficulties in speech understanding. The present pattern
      of results with Mandarin-speaking CI users is consistent with previous auditory
      working memory studies with English-speaking CI users, suggesting that the
      lexical importance of voice pitch cues (albeit poorly coded by the CI) did not
      influence the relationship between working memory and speech perception.

PMID- 24921936
TI  - Functional Mode Electron-Transfer Theory.
AB  - A solid approach has been developed to ascertain the correlation of electron
      transfer with molecular vibration in a quantitative manner. Specifically, the
      reaction coordinate is identified by maximizing the linear Pearson's correlation
      coefficient between atomic displacement and the diabatic energy gap. In the limit
      of fast molecular vibration, the rates of electron transfer driven by multiple
      vibrational modes have been derived respectively under the strong and weak
      vibronic coupling conditions. Our functional mode electron-transfer theory is
      then justified by investigating the electron transfer of a betaine-30 molecule
      from its first excited state to its ground state when being solvated in glycerol
      triacetate. Among the 210 available vibrational modes of betaine-30, only seven
      are essential to the electron transfer by cumulatively accounting for more than
      60% of the total reorganization energy. Because all essential vibrational modes
      are significantly faster than thermal fluctuation, the electron transfer is
      primarily driven by intramolecular quantum tunneling. Interestingly, the
      calculated reaction driving force of 1.95 eV is substantially greater than the
      reorganization energy of 0.58 eV, placing the reaction in the inverted Marcus
      region. Nevertheless, a sizable Franck-Condon factor of 1.58 * 10(-3) eV(-1) is
      still achieved due to the large vibronically weighted zero-point energy of the
      essential vibrational modes. After determining the electronic coupling strength
      as 0.14 eV by the constrained density functional theory, the overall electron
      transfer rate at 300 K is found to be 0.30 ps(-1), which agrees nearly perfectly
      with experimental values.

PMID- 24921937
TI  - Real-time dopamine measurement in awake monkeys.
AB  - Fast-scan cyclic voltammetry (FSCV) is often used to measure real-time dopamine
      (DA) concentrations in awake, behaving rodents. Extending this technique to work
      in monkeys would provide a platform for advanced behavioral studies and a primate
      model for preclinical research. The present study demonstrates the feasibility of
      DA recordings in two awake monkeys (Macaca mulatta) using a mixture of techniques
      adapted from rodent, primate and brain slice work. We developed a long carbon
      fiber electrode to operate in the larger primate brain. This electrode was
      lowered into the striatum each day using a recording chamber and a detachable
      micromanipulator system. A manipulator also moved one or more tungsten
      stimulating electrodes into either the nearby striatum or the ventral tegmental
      area/substantia nigra pars compacta (VTA/SNc). We developed an electrical
      stimulation controller to reduce artifacts during electrical stimulation. We also
      introduce a stimulation-based methodology for estimating distances between
      electrodes in the brain. Dopamine responses within the striatum were evoked by
      either stimulation of the striatum near the FSCV electrode, or stimulation within
      the VTA/SNc. Unexpected juice rewards also evoked dopamine responses in the
      ventral striatum. Thus, we demonstrate that robust dopamine responses can be
      recorded from awake, behaving primates with FSCV. In addition, we describe how a
      stimulation technique borrowed from the neuroprosthetics field can activate the
      distributed monkey midbrain dopamine system in a way that mimics rodent VTA
      stimulation. 

PMID- 24921938
TI  - Cu/Mn co-oxidized cyclization for the synthesis of highly substituted pyrrole
      derivatives from amino acid esters: a strategy for the biomimetic syntheses of
      lycogarubin C and chromopyrrolic acid.
AB  - An effective and concise approach to synthesis of tetrasubstituted pyrroles from
      readily available amino acid esters by the promotion of Cu(OAc)2 in conjunction
      with Mn(OAc)3 has been developed. This reaction proceeds through multiple
      dehydrogenations, deamination, and oxidative cyclization. This oxidized system
      tolerates substrates bearing various electron-donating or electron-withdrawing
      groups. With this methodology, several key intermediates of natural products have
      been effectively prepared, and the total syntheses of lycogarubin C and
      chromopyrrolic acid have been completed in high efficiency. 

PMID- 24921939
TI  - Lightweight and flexible reduced graphene oxide/water-borne polyurethane
      composites with high electrical conductivity and excellent electromagnetic
      interference shielding performance.
AB  - In this study, we developed a simple and powerful method to fabricate flexible
      and lightweight graphene-based composites that provide high electromagnetic
      interference (EMI) shielding performance. Electrospun waterborne polyurethane
      (WPU) that featured sulfonate functional groups was used as the polymer matrix,
      which was light and flexible. First, graphene oxide (GO)/WPU composites were
      prepared through layer-by-layer (L-b-L) assembly of two oppositely charged
      suspensions of GO, the cationic surfactant (didodecyldimethylammonium bromide,
      DDAB)-adsorbed GO and intrinsic negatively charged GO, depositing on the
      negatively charged WPU fibers. After the L-b-L assembly cycles, the GO bilayers
      wrapped the WPU fiber matrix completely and revealed fine connections guided by
      the electrospun WPU fibers. Then, we used hydroiodic acid (HI) to obtain highly
      reduced GO (r-GO)/WPU composites, which exhibited substantially enhanced
      electrical conductivity (approximately 16.8 S/m) and, moreover, showed a high EMI
      shielding effectiveness (approximately 34 dB) over the frequency range from 8.2
      to 12.4 GHz. 

PMID- 24921940
TI  - Response to 'Imprecise diagnosis of migraine with aura in the Women's Health
      Study. Does it matter?'.

PMID- 24921941
TI  - Performance of parasitological and molecular techniques for the diagnosis and
      surveillance of gambiense sleeping sickness.
AB  - OBJECTIVES: Recently, improvements have been made to diagnostics for gambiense
      sleeping sickness control but their performance remains poorly documented and may
      depend on specimen processing prior to examination. In a prospective study in the
      Democratic Republic of the Congo, we compared the diagnostic performance of
      several parasite detection techniques, immune trypanolysis and of m18S PCR on
      whole blood stored in a stabilisation buffer or dried on filter paper. METHODS:
      Individuals with CATT whole blood (WB) titer >=1?4 or with clinical signs
      indicative for sleeping sickness were examined for presence of trypanosomes in
      lymph node aspirate (LNA) and/or in blood. Blood was examined with Capillary
      Centrifugation Technique (CTC), mini-Anion Exchange Centrifugation Technique
      (mAECT) and mAECT on buffy coat (BC). PCR was performed on whole blood (i) stored
      in guanidine hydrochloride EDTA (GE) stabilisation buffer and (ii) dried on
      filter paper, and repeatability and reproducibility were assessed. Immune
      trypanolysis (TL) was performed on plasma. RESULTS: A total of 237 persons were
      included. Among 143 parasitologically confirmed cases, 85.3% had a CATT-WB titre
      of >=1/8, 39.2% were positive in LNA, 47.5% in CTC, 80.4% in mAECT-WB, 90.9% in
      mAECT-BC, 95.1% in TL and up to 89.5% in PCR on GE-stabilised blood. PCR on GE
      stabilised blood showed highest repeatability (87.8%) and inter-laboratory
      reproducibility (86.9%). Of the 94 non-confirmed suspects, respectively 39.4% and
      23.4% were TL or PCR positive. Suboptimal specificity of PCR and TL was also
      suggested by latent class analysis. CONCLUSION: The combination of LNA
      examination with mAECT-BC offered excellent diagnostic sensitivity. For PCR,
      storage of blood in stabilisation buffer is to be preferred over filter paper. TL
      as well as PCR are useful for remote diagnosis but are not more sensitive than
      mAECT-BC. For TL and PCR, the specificity, and thus usefulness for management of
      non-confirmed suspects remain to be determined.

PMID- 24921942
TI  - Inhibition of the polyamine system counteracts beta-amyloid peptide-induced
      memory impairment in mice: involvement of extrasynaptic NMDA receptors.
AB  - In Alzheimer's disease (AD), the beta-amyloid peptide (Abeta) has been causally
      linked to synaptic dysfunction and cognitive impairment. Several studies have
      shown that N-Methyl-D-Aspartate receptors (NMDAR) activation is involved in the
      detrimental actions of Abeta. Polyamines, like spermidine and spermine, are
      positive modulators of NMDAR function and it has been shown that their levels are
      regulated by Abeta. In this study we show here that interruption of NMDAR
      modulation by polyamines through blockade of its binding site at NMDAR by arcaine
      (0.02 nmol/site), or inhibition of polyamine synthesis by DFMO (2.7 nmol/site),
      reverses Abeta25-35-induced memory impairment in mice in a novel object
      recognition task. Incubation of hippocampal cell cultures with Abeta25-35 (10 uM)
      significantly increased the nuclear accumulation of Jacob, which is a hallmark of
      NMDAR activation. The Abeta-induced nuclear translocation of Jacob was blocked
      upon application of traxoprodil (4 nM), arcaine (4 uM) or DFMO (5 uM), suggesting
      that activation of the polyamine binding site at NMDAR located probably at
      extrasynaptic sites might underlie the cognitive deficits of Abeta25-35-treated
      mice. Extrasynaptic NMDAR activation in primary neurons results in a stripping of
      synaptic contacts and simplification of neuronal cytoarchitecture. Abeta25-35
      application in hippocampal primary cell cultures reduced dendritic spine density
      and induced alterations on spine morphology. Application of traxoprodil (4 nM),
      arcaine (4 uM) or DFMO (5 uM) reversed these effects of Abeta25-35. Taken
      together these data provide evidence that polyamine modulation of extrasynaptic
      NMDAR signaling might be involved in Abeta pathology. 

PMID- 24921943
TI  - PPARgamma negatively regulates T cell activation to prevent follicular helper T
      cells and germinal center formation.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription
      factor that regulates lipid and glucose metabolism. Although studies of PPARgamma
      ligands have demonstrated its regulatory functions in inflammation and adaptive
      immunity, its intrinsic role in T cells and autoimmunity has yet to be fully
      elucidated. Here we used CD4-PPARgammaKO mice to investigate PPARgamma-deficient
      T cells, which were hyper-reactive to produce higher levels of cytokines and
      exhibited greater proliferation than wild type T cells with increased ERK and AKT
      phosphorylation. Diminished expression of IkappaBalpha, Sirt1, and Foxo1, which
      are inhibitors of NF-kappaB, was observed in PPARgamma-deficient T cells that
      were prone to produce all the signature cytokines under Th1, Th2, Th17, and Th9
      skewing condition. Interestingly, 1-year-old CD4-PPARgammaKO mice spontaneously
      developed moderate autoimmune phenotype by increased activated T cells,
      follicular helper T cells (TFH cells) and germinal center B cells with glomerular
      inflammation and enhanced autoantibody production. Sheep red blood cell
      immunization more induced TFH cells and germinal centers in CD4-PPARgammaKO mice
      and the T cells showed increased of Bcl-6 and IL-21 expression suggesting its
      regulatory role in germinal center reaction. Collectively, these results suggest
      that PPARgamma has a regulatory role for TFH cells and germinal center reaction
      to prevent autoimmunity. 

PMID- 24921944
TI  - A human monoclonal antibody targeting the stem cell factor receptor (c-Kit)
      blocks tumor cell signaling and inhibits tumor growth.
AB  - Stem cell factor receptor (c-Kit) exerts multiple biological effects on target
      cells upon binding its ligand stem cell factor (SCF). Aberrant activation of c
      Kit results in dysregulated signaling and is implicated in the pathogenesis of
      numerous cancers. The development of more specific and effective c-Kit therapies
      is warranted given its essential role in tumorigenesis. In this study, we
      describe the biological properties of CK6, a fully human IgG1 monoclonal antibody
      against the extracellular region of human c-Kit. CK6 specifically binds c-Kit
      receptor with high affinity (EC 50 = 0.06 nM) and strongly blocks its interaction
      with SCF (IC 50 = 0.41 nM) in solid phase assays. Flow cytometry shows CK6
      binding to c-Kit on the cell surface of human small cell lung carcinoma (SCLC),
      melanoma, and leukemia tumor cell lines. Furthermore, exposure to CK6 inhibits
      SCF stimulation of c-Kit tyrosine kinase activity and downstream signaling
      pathways such as mitogen-activated protein kinase (MAPK) and protein kinase B
      (AKT), in addition to reducing tumor cell line growth in vitro. CK6 treatment
      significantly decreases human xenograft tumor growth in NCI-H526 SCLC (T/C% = 57)
      and Malme-3M melanoma (T/C% = 58) models in vivo. The combination of CK6 with
      standard of care chemotherapy agents, cisplatin and etoposide for SCLC or
      dacarbazine for melanoma, more potently reduces tumor growth (SCLC T/C% = 24,
      melanoma T/C% = 38) compared with CK6 or chemotherapy alone. In summary, our
      results demonstrate that CK6 is a c-Kit antagonist antibody with tumor growth
      neutralizing properties and are highly suggestive of potential therapeutic
      application in treating human malignancies harboring c-Kit receptor. 

PMID- 24921945
TI  - Resource supply overrides temperature as a controlling factor of marine
      phytoplankton growth.
AB  - The universal temperature dependence of metabolic rates has been used to predict
      how ocean biology will respond to ocean warming. Determining the temperature
      sensitivity of phytoplankton metabolism and growth is of special importance
      because this group of organisms is responsible for nearly half of global primary
      production, sustains most marine food webs, and contributes to regulate the
      exchange of CO2 between the ocean and the atmosphere. Phytoplankton growth rates
      increase with temperature under optimal growth conditions in the laboratory, but
      it is unclear whether the same degree of temperature dependence exists in nature,
      where resources are often limiting. Here we use concurrent measurements of
      phytoplankton biomass and carbon fixation rates in polar, temperate and tropical
      regions to determine the role of temperature and resource supply in controlling
      the large-scale variability of in situ metabolic rates. We identify a
      biogeographic pattern in phytoplankton metabolic rates, which increase from the
      oligotrophic subtropical gyres to temperate regions and then coastal waters.
      Variability in phytoplankton growth is driven by changes in resource supply and
      appears to be independent of seawater temperature. The lack of temperature
      sensitivity of realized phytoplankton growth is consistent with the limited
      applicability of Arrhenius enzymatic kinetics when substrate concentrations are
      low. Our results suggest that, due to widespread resource limitation in the
      ocean, the direct effect of sea surface warming upon phytoplankton growth and
      productivity may be smaller than anticipated. 

PMID- 24921946
TI  - Grazing behaviour of a non-herbivorous characin: revisiting plasticity.
AB  - Feeding behaviour and diet of Bryconamericus microcephalus differed between
      canopy conditions. At the open canopy site, a behavioural modification, grazing
      on algae, was observed. This was also reflected in gut content analysis and
      suggests behavioural plasticity in response to resource availability. 

PMID- 24921947
TI  - Pure chondrosarcomas of the uterus: a rare uterine tumour.

PMID- 24921949
TI  - Heteronuclear proton double quantum-carbon single quantum scalar correlation in
      solids.
AB  - A new NMR experiment that exploits the advantages of proton double quantum (DQ)
      NMR through a proton DQ-carbon single quantum (SQ) correlation experiment in the
      solid state is proposed. Analogous to the previously proposed 2D (1)H (DQ)-(13)C
      refocused INEPT experiment (Webber et al., 2010), the correlation between (1)H
      and (13)C is achieved through scalar coupling evolution, while the double quantum
      coherence among protons is generated through dipolar couplings. However, the new
      experiment relies on (13)C transverse coherence for scalar transfer. The new
      experiment dubbed MAS-J-(1)H (DQ)-(13)C-HMQC, is particularly suited for
      unlabeled molecules and can provide higher sensitivity than its INEPT
      counterpart. The experiment is applied to four different samples. 

PMID- 24921948
TI  - Intervention effects on adolescent physical activity in the multicomponent SPACE
      study: a cluster randomized controlled trial.
AB  - BACKGROUND: Multicomponent school-based interventions have the potential to
      reduce the age-related decline in adolescents' physical activity (PA), yet there
      is not consistent evidence to guide non-curricular and school environment
      interventions. The aim of this study was to assess the effectiveness of a
      multicomponent environmental school-based intervention, designed to reduce the
      age-related decline in PA among adolescents. METHODS: A cluster randomized
      controlled trial was conducted with 7 intervention and 7 control schools.
      Baseline measurements were carried out in spring 2010 with 2 years of follow-up.
      A total of 1,348 students (11-13 years, in grade 5 and 6) enrolled in the study
      at baseline. The 14 schools included in the study were located in the Region of
      Southern Denmark. The intervention consisted of organizational and physical
      changes in the school environment with a total of 11 intervention components. The
      primary outcome measure was overall PA (cpm, counts per minute) and was supported
      by analyses of time spent in MVPA, and time spent sedentary. Furthermore, a
      secondary outcome measure was PA in school time and during recess. PA was
      measured using accelerometer (Actigraph GT3X). RESULTS: A total of 797 students
      completed the trial and had valid accelerometer data. No significant difference
      was found for overall PA with an adjusted difference of -19.1 cpm (95% CI: -93,
      53) or for school time activity with an adjusted difference of 6 cpm (95% CI: 
      73, 85). A sensitivity analysis revealed a positive significant intervention
      effect of PA in recess with an adjusted difference of 95 cpm. CONCLUSIONS: No
      evidence was found of the overall effect of a non-curricular multicomponent
      school-based intervention on PA among Danish adolescents. The intervention was
      positively associated with PA during school time and recess, however, with small
      estimates. Lack of effect on overall PA could be due to both program theory and
      different degrees of implementation. TRIAL REGISTRATION: www.Controlled
      Trials.com ISRCTN79122411.

PMID- 24921950
TI  - One-pot fabrication of rattle-like capsules with multicores by pickering-based
      polymerization with nanoparticle nucleation.
AB  - Rattle-like polymer capsules with multicores in one shell are facilely fabricated
      by oil-in-water Pickering emulsion polymerization for the first time. The oil
      phase contains hydrophobic silica nanoparticles dispersed in polymerizable
      monomer, styrene, and unpolymerizable solvent, hexadecane. The multicore rattle
      like capsules are facilely produced after the polymerization of monomers in the
      oil droplets. The key point of this one-pot method lies in the nucleation of
      hydrophobic silica and the phase separation between the resulting polystyrene and
      hexadecane. The influences of the contents of silica, hexadecane, cross-linker,
      and stabilizer on the structure and morphology of rattle-like capsules are
      systematically investigated. Moreover, functionalization of the rattle-like
      capsules can be developed easily by varying hydrophobic nucleation nanoparticles
      in the oil phase. This work opens up a new route to fabricate multilevel capsules
      or spheres. 

PMID- 24921951
TI  - Phase transitions and chain dynamics of surfactants intercalated into the
      galleries of naturally occurring clay mineral magadiite.
AB  - We investigate conformational dynamics and phase transitions of surfactant
      molecules confined in the layered galleries of the organo-modified, natural
      polysilicate clay, magadiite. We have shown that our approach to studying this
      class of materials is capable of delivering detailed information on the molecular
      mobility of the confined molecules. From the analysis of the measured
      heteronuclear dipolar couplings, the orientational order parameters of the C-H
      bonds along the hydrocarbon chain have been determined. Three phases have been
      observed in the nanocomposite, characterized by distinct dynamical states of the
      surfactant. At room temperature, restricted mobility of the molecules led to the
      adoption of an essentially all-trans conformation by the chains. This behavior
      can be described by a model incorporating small-angle wobbling around the long
      molecular axes of the chains. Upon heating, dynamic transformation takes place,
      resulting in a rotator type solid phase where molecules in extended all-trans
      conformations undergo fast and unrestricted rotation about their respective
      symmetry axes. The second phase transition is associated with chain melting and
      the onset of translational dynamics and results in an essentially liquid
      crystalline-like state of the organic component. The mobility of the surfactant
      is one of the key factors facilitating the efficient penetration of
      macromolecules in the process of preparing of polymer/organoclay nanocomposites.
      The exploration of dynamic properties of the functionalizing organic layer should
      provide important input into the improved design of new organic-inorganic hybrid
      materials. 

PMID- 24921952
TI  - Is the pain visual analogue scale linear and responsive to change? An exploration
      using Rasch analysis.
AB  - OBJECTIVES: Pain visual analogue scales (VAS) are commonly used in clinical
      trials and are often treated as an interval level scale without evidence that
      this is appropriate. This paper examines the internal construct validity and
      responsiveness of the pain VAS using Rasch analysis. METHODS: Patients (n = 221,
      mean age 67, 58% female) with chronic stable joint pain (hip 40% or knee 60%) of
      mechanical origin waiting for joint replacement were included. Pain was scored on
      seven daily VASs. Rasch analysis was used to examine fit to the Rasch model.
      Responsiveness (Standardized Response Means, SRM) was examined on the raw ordinal
      data and the interval data generated from the Rasch analysis. RESULTS: Baseline
      pain VAS scores fitted the Rasch model, although 15 aberrant cases impacted on
      unidimensionality. There was some local dependency between items but this did not
      significantly affect the person estimates of pain. Daily pain (item difficulty)
      was stable, suggesting that single measures can be used. Overall, the SRMs
      derived from ordinal data overestimated the true responsiveness by 59%. Changes
      over time at the lower and higher end of the scale were represented by large
      jumps in interval equivalent data points; in the middle of the scale the reverse
      was seen. CONCLUSIONS: The pain VAS is a valid tool for measuring pain at one
      point in time. However, the pain VAS does not behave linearly and SRMs vary along
      the trait of pain. Consequently, Minimum Clinically Important Differences using
      raw data, or change scores in general, are invalid as these will either under- or
      overestimate true change; raw pain VAS data should not be used as a primary
      outcome measure or to inform parametric-based Randomised Controlled Trial power
      calculations in research studies; and Rasch analysis should be used to convert
      ordinal data to interval data prior to data interpretation.

PMID- 24921953
TI  - A RRKM study and a DFT assessment on gas-phase fragmentation of formamide-M(2+)
      (M = Ca, Sr).
AB  - A kinetic study of the unimolecular reactivity of formamide-M(2+) (M = Ca, Sr)
      systems was carried out by means of RRKM statistical theory using high-level DFT.
      The results predict M(2+), [M(NH2)](+) and [HCO](+) as the main products,
      together with an intermediate that could eventually evolve to produce
      [M(NH3)](2+) and CO, for high values of internal energy. In this framework, we
      also evaluated the influence of the external rotational energy on the reaction
      rate constants. In order to find a method to perform reliable electronic
      structure calculations for formamide-M(2+) (M = Ca, Sr) at a relatively low
      computational cost, an assessment of different methods was performed. In the
      first assessment twenty-one functionals, belonging to different DFT categories,
      and an MP2 wave function method using a small basis set were evaluated.
      CCSD(T)/cc-pWCVTZ single point calculations were used as reference. A second
      assessment has been performed on geometries and energies. We found BLYP/6-31G(d)
      and G96LYP/6-31+G(d,p) as the best performing methods, for formamide-Ca(2+) and
      formamide-Sr(2+), respectively. Furthermore, a detailed assessment was done on
      RRKM reactivity and G96LYP/6-31G(d) provided results in agreement with higher
      level calculations. The combination of geometrical, energetics and kinetics
      (RRKM) criteria to evaluate DFT functionals is rather unusual and provides an
      original assessment procedure. Overall, we suggest using G96LYP as the best
      performing functional with a small basis set for both systems. 

PMID- 24921955
TI  - Stand-alone Cipralex Symposium, Lisbon, 2006.

PMID- 24921956
TI  - Guidelines in major depressive disorder, and their limitations.
AB  - Depression is a highly disabling, recurrent disease that imposes a significant
      burden on the individual, their close contacts, and on society. Despite the
      existence of treatment guidelines for major depression, management frequently
      falls short of these recommendations, sometimes due to inadequate doses or
      duration of prescribed antidepressant medication; at other times secondary to
      patient non-adherence to the recommended treatment. Evidence-based treatment
      guidelines developed by the major mental health organizations advise that
      patients who have experienced either a first or a recurrent episode of major
      depression should receive continued therapeutic doses of medication for at least
      4-6 months following symptom remission, to reduce the risk of relapse. Further to
      this, antidepressant prophylaxis is beneficial in any patient with a history of
      three or more major depressive episodes, or two or more episodes in the last 5
      years. Selective serotonin reuptake inhibitors (SSRIs) have demonstrated
      excellent efficacy and tolerability in the treatment and prophylaxis of major
      depression, as well as being associated with significant reduction in suicide
      risk in some populations. Escitalopram, an atypical SSRI that has shown
      superiority to conventional SSRIs and venlafaxine in clinical studies, has
      demonstrated particular benefits in severely depressed patients, in whom its
      efficacy appears to increase with increasing severity of depression. In the
      absence of formal treatment guidelines for severe depression, or comborbid
      depression and anxiety, escitalopram appears to be a logical treatment choice. 

PMID- 24921957
TI  - The new guidelines from the British Association for Psychopharmacology for
      anxiety disorders.
AB  - Anxiety disorders, which often commence in childhood, are among the most common
      psychological disorders encountered in primary care practice, with 1 year and
      lifetime prevalence (excluding post-traumatic stress disorder) of 12.0 and 21.1%,
      respectively. Because of their wide range of clinical presentation and
      comorbidity with other disorders such as depression, they are frequently under
      recognized. These factors, coupled with lack of physician confidence in their
      ability to treat these conditions, leads to under-treatment. Treatment of anxiety
      disorders is further complicated by a significant lag time between first onset
      and initial contact with a treatment provider. Even for those anxiety disorders
      characterized by relatively early treatment contact (i.e. panic disorder and
      generalized anxiety disorder), <50% of patients are treated at first onset of
      symptoms. Following treatment, approximately 50% of patients significantly
      improve over 6-16 months, but complete recovery is uncommon. To help remedy this
      situation, the British Association for Pharmacology (BAP) has issued
      comprehensive evidence-based guidelines (developed from a consensus meeting 20-21
      May 2004 involving clinical experts and representatives of user groups) to aid
      clinicians in diagnosing and treating anxiety disorders. The guidelines focus on
      pharmacological interventions for all primary anxiety disorders in adults (18-65
      years), and are intended for doctors in primary care, as well as specialist
      practice. Importantly, the guidelines cover the difficult topic of treatment non
      response. The BAP guidelines link treatment recommendations with quality of
      evidence, allowing clinicians to judge the confidence they might place in
      particular recommendations. 

PMID- 24921958
TI  - Challenges in the treatment of anxiety disorders: beyond guidelines.
AB  - Anxiety disorders are highly prevalent, come in many forms and are often chronic,
      with many patients requiring long-term maintenance therapy. Anxiety and
      depression may also be comorbid in up to 50% of patients, leading to problems
      during diagnosis and treatment. Despite their frequency, the recognition and
      treatment of anxiety disorders is frequently suboptimal, with as few as 15% of
      patients obtaining treatment consistent with evidence-based care recommendations.
      Current treatment guidelines for anxiety disorders include a range of
      pharmacological and non-pharmacological approaches. However, the use of these
      guidelines alone may not be sufficient to improve patient outcomes. Optimal
      treatments for anxiety should be based on chronic disease management and balance
      efficacy with long-term tolerability. Current first-line therapies should include
      broad-spectrum agents that have proven efficacy in treating both anxiety and
      depression and are effective across all treatment phases. The allosteric
      serotonin reuptake inhibitor (ASRI), escitalopram, is a particularly effective
      treatment, offering high rates of remission combined with relatively low rates of
      discontinuation due to adverse events. Combination therapy involving medication
      and psychological approaches, e.g., cognitive behavioral therapy, may also be
      helpful. Novel approaches to delivering psychotherapy and self-management via the
      Internet may address accessibility issues for evidence-based psychological
      treatments. 

PMID- 24921959
TI  - Closing the antidepressant efficacy gap between clinical trials and real patient
      populations.
AB  - Overall, patient outcomes in the primary care of depression are seldom as good as
      those achieved in clinical trials - the "efficacy gap". Many factors contribute
      to this, including poor patient compliance, poor family and social support and
      negative media reporting of antidepressants. Indeed, negative media reporting has
      had far more impact on physicians' prescribing of antidepressants than have
      regulatory agencies, partly as a result of changing public attitudes. Negative
      media reports linking SSRIs to increased child suicide rates have also resulted
      in a decline in the prescribing of SSRIs to this age group, but with no
      concomitant increase in the prescribing of fluoxetine, the only antidepressant
      recommended for the treatment of children. There are also inadequacies in the
      guidelines available to primary care givers that might contribute to the efficacy
      gap. Guidelines can be too specific for clinical practice - especially where
      depression coexists with anxiety disorders - and too passive, resulting in
      delayed or inadequate intervention. Evidence suggests that many physicians prefer
      to be more proactive. In the recent AHEAD survey, physicians identified faster
      resolution of symptoms as the property most desirable for improving
      antidepressant therapy. There is recent evidence that structured long-term
      therapy and easily-implemented measurement-based care procedures can improve
      remission rates and help bridge the efficacy gap. If these can be allied with
      greater public/media understanding of depression and its treatment, along with
      improved guidelines, then significant progress can be anticipated in the
      management of mood disorders. 

PMID- 24921960
TI  - Synthesis of nucleobase-caged peptide nucleic acids having improved photochemical
      properties.
AB  - A nucleobase-caged peptide nucleic acid (PNA) having a (6-bromo-7
      methoxycoumarin)-4-ylmethoxycarbonyl (Bmcmoc) caging group was newly synthesized.
      The Bmcmoc-caged PNAs were photolyzed to produce parent PNAs with a high
      photochemical efficiency. Introduction of a single Bmcmoc group was sufficient to
      suppress polymerase chain reaction (PCR) clamping activity and triplex invasion
      complex formation. Photo-mediated restoration of the PCR clamping activity was
      also demonstrated. 

PMID- 24921961
TI  - Dry paths effectively reduce road mortality of small and medium-sized terrestrial
      vertebrates.
AB  - Wildlife passages are widely used mitigation measures designed to reduce the
      adverse impacts of roads on animals. We investigated whether road kills of small
      and medium-sized terrestrial vertebrates can be reduced by constructing dry paths
      adjacent to streams that pass under road bridges. The study was carried out in
      southern Finland during the summer of 2008. We selected ten road bridges with dry
      paths and ten bridges without them, and an individual dry land reference site for
      each study bridge on the basis of landscape and traffic features. A total of 307
      dead terrestrial vertebrates were identified during the ten-week study period.
      The presence of dry paths decreased the amount of road-killed terrestrial
      vertebrates (Poisson GLMM; p < 0.001). That was true also when considering
      amphibians alone (p < 0.001). The evidence on road-kills on mammals was not such
      clear. In the mammal model, a lack of dry paths increased the amount of carcasses
      (p = 0.001) whereas the number of casualties at dry path bridges was comparable
      with dry land reference sites. A direct comparison of the dead ratios suggests an
      average efficiency of 79% for the dry paths. When considering amphibians and
      mammals alone, the computed effectiveness was 88 and 70%, respectively. Our
      results demonstrate that dry paths under road bridges can effectively reduce road
      kills of small and medium-sized terrestrial vertebrates, even without guiding
      fences. Dry paths seemed to especially benefit amphibians which are a threatened
      species group worldwide and known to suffer high traffic mortality. 

PMID- 24921962
TI  - Role of primary substrate composition and concentration on attenuation of trace
      organic chemicals in managed aquifer recharge systems.
AB  - This study was undertaken to investigate the role of primary substrate
      composition and concentration on the attenuation of biodegradable emerging trace
      organic chemicals (TOrCs) in simulated managed aquifer recharge (MAR) systems.
      Four sets of soil columns were established in the laboratory, each receiving
      synthetic feed solutions comprising different ratios and concentrations of
      peptone-yeast and humic acid as the primary substrate to investigate the effect
      on removal of six TOrCs (atenolol, caffeine, diclofenac, gemfibrozil, primidone,
      and trimethoprim). Based on abiotic control experiments, adsorption was not
      identified as a significant attenuation mechanism for primidone, gemfibrozil and
      diclofenac. Caffeine, atenolol and trimethoprim displayed initial adsorptive
      losses, however, adsorption coefficients derived from batch tests confirmed that
      adsorption was limited and in the long-term experiment, biodegradation was the
      dominant attenuation process. Within a travel time of 16 h, caffeine - an easily
      degradable compound exhibited removal exceeding 75% regardless of composition or
      concentration of the primary substrate. Primidone - a poorly degradable compound,
      showed no removal in any column regardless of the nature of the primary
      substrate. The composition and concentration of the primary substrate, however,
      had an effect on attenuation of moderately degradable TOrCs, such as atenolol,
      gemfibrozil and diclofenac, with the primary substrate composition seeming to
      have a larger impact on TOrC attenuation than its concentration. When the primary
      substrate consisted mainly of refractory substrate (humic acid), higher removal
      of the moderately degradable TOrCs was observed. The microbial communities in the
      columns receiving more refractory carbon, were noted to be more diverse and hence
      likely able to express a wider range of enzymes, which were more suitable for
      TOrC transformation. The effect of the primary substrate on microbial community
      composition, diversity and gene expression potential confirmed its influence on
      TOrC degradation. 

PMID- 24921963
TI  - The role of social values in the management of ecological systems.
AB  - The concept of value is central to the practice and science of ecological
      management and conservation. There is a well-developed body of theory and
      evidence that explores concepts of value in different ways across different
      disciplines including philosophy, economics, sociology and psychology. Insight
      from these disciplines provides a robust and sophisticated platform for
      considering the role of social values in ecological conservation, management and
      research. This paper reviews theories of value from these disciplines and
      discusses practical tools and instruments that can be utilised by researchers and
      practitioners. A distinction is highlighted between underlying values that shape
      people's perception of the world (e.g. altruistic or biospheric value
      orientations), and the values that people assign to things in the world (e.g.
      natural heritage, money). Evidence from numerous studies has shown that there are
      multiple pathways between these values and attitudes, beliefs and behaviours
      relevant to ecological management and conservation. In an age of increasing
      anthropogenic impacts on natural systems, recognising how and why people value
      different aspects of ecological systems can allow ecological managers to act to
      minimise conflict between stakeholders and promote the social acceptability of
      management activities. A series of practical guidelines are provided to enable
      social values to be better considered in ecosystem management and research. 

PMID- 24921964
TI  - Is environmental management an economically sustainable business?
AB  - This paper investigates whether environmental management is an economically
      sustainable business. While firms invest in green production and green supply
      chain activities with the primary purpose of reducing their environmental impact,
      the reciprocal relationships with economic performance need to be clarified.
      Would firms and suppliers adjust their environmental strategies if the higher
      economic value that environmental management generates is reinvested in greening
      actions? We found out that environmental management positively influences
      economic performance as second order (long term) target, to be reached
      conditioned by higher environmental performance; in addition, firms can increase
      their performance if they reinvest the higher economic value gained through
      environmental management in green practices: While investing in environmental
      management programs is a short term strategy, economic rewards can be obtained
      only with some delays. Consequently, environmental management is an economically
      sustainable business only for patient firms. In the evaluation of these
      reciprocal relationships, we discovered that green supply chain initiatives are
      more effective and more economically sustainable than internal actions. 

PMID- 24921965
TI  - Development of an electrochemical sensor based on the catalysis of ferrocene
      actuated hemin/G-quadruplex enzyme for the detection of potassium ions.
AB  - Sensitive and selective sensors need to be explored to detect the physiological
      potassium level due to its important role in the living organisms. In the present
      system, a novel electron transfer mediator actuated electrocatalytical biosensor
      was demonstrated to assay K(+) based on the conformational change of DNA. With
      the hybridization between the complementary bases and the self-folding of guanine
      rich nucleic acid sequence, the horseradish peroxidase-mimicking enzyme (HRP
      DNAzyme) was formed and brought to approach the ferrocene (Fc) unit on Au
      nanoparticles (AuNPs). Thus, in the system, Fc unit acted as the relay,
      stimulating the electrical contact of HRP-DNAzyme with the electrode to obtain
      the bioelectrocatalyze reduction signal. Under the Fc actuated catalysis of HRP
      DNAzyme and amplification of Au nanoparticles, the obtained biosensor exhibited a
      sensitive detection for K(+). A satisfying result of a wide linear range and low
      detection limit were obtained with the novel electrocatalytical biosensor which
      was then applied in real samples. 

PMID- 24921966
TI  - Priority setting for evaluation: developing a strategic evaluation portfolio.
AB  - Resources for evaluation are frequently scarce and best use should be made of
      them to deliver against the typical purposes of an evaluation function to (i)
      enhance accountability and (ii) promote operational improvement and learning.
      This paper presents a method for analyzing and prioritizing potential evaluations
      to improve the selection of a portfolio of activities that give the greatest pay
      off. The method establishes the relative priority of 'evaluation opportunities'
      against criteria that relate to the usual primary purposes of an evaluation
      function. The method was developed in the context of a multilateral organization
      but is of general utility to the wider evaluation community and, with suitable
      adaptation can be applied to help ensure that scarce evaluation resources are
      used to their best advantage. A range of benefits are expected to accrue to an
      organization from adopting a more thorough, analytical priority setting process.
      These include: The paper describes a priority setting method, including the key
      criteria that are used to assess 'evaluation opportunities', and presents
      different analyses of an evaluation portfolio. Examples from a practical
      application of the approach to the preparation of an evaluation work plan in a
      multilateral environmental agency are given.

PMID- 24921967
TI  - Regional itching and hyperhidrosis in myeloproliferative disorder with fibrosis:
      studies on a muscarinic cholinergic receptor M3.

PMID- 24921968
TI  - Perception of risk of HIV infections and sexual behaviour of the sexually active
      university students in Zimbabwe.
AB  - The study sought to establish university students' perceptions of risk of HIV
      infections. A cross-sectional survey was conducted on 345 sexually active
      students at two universities in Zimbabwe (one state and one private). Results
      revealed that above a quarter of the respondents felt at risk of getting HIV due
      to their regular partners' sexual behaviours and more than half felt at risk of
      getting HIV due to their casual partners' sexual behaviours. In addition, a third
      of the respondents acknowledged the HIV risk due to their own sexual behaviours.
      More state university respondents felt exposed to HIV infections due to own
      sexual behaviours than their private university counterparts. Despite these
      revelations, only 66.56% had earlier thought of their chances of getting infected
      with HIV. Personal HIV risk perceptions were low, reported by 27.76% of the
      sexually active respondents. Almost all respondents described their fellows'
      sexual behaviours as either risky or very risky.

PMID- 24921969
TI  - Pallidal stimulation in Parkinson's disease does not induce apathy.
AB  - BACKGROUND: Whereas apathy is known as a common consequence of subthalamic
      nucleus deep brain stimulation in Parkinson's disease, few studies have
      investigated the psychiatric consequences of internal globus pallidus deep brain
      stimulation. METHOD: Twenty consecutive parkinsonian patients who underwent
      bilateral pallidal stimulation were assessed 3 months prior to surgery (M-3) and
      at both 3 (M3) and 6 months (M6) after surgery, using psychiatric,
      neuropsychological, and motor scales. Apathy, mood state, and anxiety state were
      scored using the Apathy Evaluation Scale, the Montgomery-Asberg Depression Rating
      Scale, and the anxiety scale from the Association for Methodology and
      Documentation in Psychiatry, respectively. RESULTS: The mean apathy score
      remained stable between the preoperative M-3 assessment (37.2+/-6.2) and both the
      postoperative M3 (36.9+/-7.5) and M6 (37.2+/-5.0) assessments. The mean
      depression score did not differ between the M-3 assessment and M3 and M6
      assessments. There was no difference between the preoperative mean anxiety score
      and both the postoperative M3 and M6 scores. The mean score for the Mattis
      Dementia Rating Scale remained stable at each study visit. CONCLUSIONS: The main
      result of this study is the absence of deterioration in psychiatric and cognitive
      scores 3 months and 6 months after pallidal stimulation.

PMID- 24921970
TI  - Small-molecule EGFR tyrosine kinase inhibitors for the treatment of cancer.
AB  - INTRODUCTION: EGFR has been implicated in various malignancies such as NSCLC,
      breast, head and neck, and pancreatic cancer. Numerous drugs have been developed
      in order to target the tyrosine domain of EGFR as an approach in cancer
      treatment. AREAS COVERED: This article focuses on the different generations of
      EGFR tyrosine kinase inhibitors (TKIs). This spans from the emergence of the
      first-generation EGFR-TKIs to overcoming drug resistance using second-generation
      EGFR-TKIs and to reducing adverse effect (AE) using mutant-selective third
      generation EGFR-TKIs. EXPERT OPINION: Current TKI treatment is frequently
      accompanied by drug resistance and/or serious AEs. There has been the promise of
      advancements in second-generation EGFR-TKIs that could overcome drug resistance,
      acting as second- or third-line salvage treatment, but this promise has yet to be
      met. That being said, both issues are currently being addressed with mutant
      selective EGFR-TKIs with the expectation of bringing more EGFR-targeted therapy
      into the next phase of cancer therapy in the future.

PMID- 24921971
TI  - Fluorescence in rhoda- and iridacyclopentadienes neglecting the spin-orbit
      coupling of the heavy atom: the ligand dominates.
AB  - We present a detailed photophysical study and theoretical analysis of 2,5
      bis(arylethynyl)rhodacyclopenta-2,4-dienes (1a-c and 2a-c) and a 2,5
      bis(arylethynyl)iridacyclopenta-2,4-diene (3). Despite the presence of heavy
      atoms, these systems display unusually intense fluorescence from the S1 excited
      state and no phosphorescence from T1. The S1 -> T1 intersystem crossing (ISC) is
      remarkably slow with a rate constant of 108 s-1 (i.e., on the nanosecond time
      scale). Traditionally, for organometallic systems bearing 4d or 5d metals, ISC is
      2-3 orders of magnitude faster. Emission lifetime measurements suggest that the
      title compounds undergo S1 -> T1 interconversion mainly via a thermally activated
      ISC channel above 233 K. The associated experimental activation energy is found
      to be DeltaHISC = 28 kJ mol-1 (2340 cm-1) for 1a, which is supported by density
      functional theory (DFT) and time-dependent DFT calculations [DeltaHISC(calc.) =
      11 kJ mol-1 (920 cm-1) for 1a-H]. However, below 233 K a second, temperature
      independent ISC process via spin-orbit coupling occurs. The calculated lifetime
      for this S1 -> T1 ISC process is 1.1 s, indicating that although this is the main
      path for triplet state formation upon photoexcitation in common organometallic
      luminophores, it plays a minor role in our Rh compounds. Thus, the organic pi
      chromophore ligand seems to neglect the presence of the heavy rhodium or iridium
      atom, winning control over the excited-state photophysical behavior. This is
      attributed to a large energy separation of the ligand-centered highest occupied
      molecular orbital (HOMO) and lowest unoccupied MO (LUMO) from the metal-centered
      orbitals. The lowest excited states S1 and T1 arise exclusively from a HOMO-to
      LUMO transition. The weak metal participation and the cumulenic distortion of the
      T1 state associated with a large S1-T1 energy separation favor an "organic-like"
      photophysical behavior.

PMID- 24921972
TI  - Changes in the rheological properties of wheat dough during short-term storage of
      wheat.
AB  - BACKGROUND: The aim of the present study was to investigate the ability of the
      small- and large-deformation fundamental rheological tests to monitor the changes
      during short-term post-harvest storage of wheat. RESULTS: At the end of wheat
      storage period, wet gluten quantity decreased, while gluten index increased in
      comparison to those of freshly harvested samples. The rheological properties of
      dough changed over the pre-defined period of storage in terms of becoming more
      elastic and less extensible in comparison to that of freshly harvested wheat.
      Visco-elastic properties of weaker flour samples changed more markedly during
      storage than those of stronger flours, indicating that the intensity of dough
      rheological changes during wheat storage might be dependent on gluten quality and
      were the characteristic of wheat variety. CONCLUSION: It was shown that small
      deformation dynamic oscillation and large deformation creep-recovery tests can be
      successfully employed to monitor the changes in flour quality during wheat
      storage and that required storage period after wheat harvesting has to be defined
      according to wheat variety initial rheological properties and its gluten quality.

PMID- 24921974
TI  - Self-assembly of an all-thiol-stabilized {Ag28S23} high-nuclearity luminescent
      nanocluster with a "crab-like" shape.
AB  - We report a rare all-thiol-stabilized [Ag28(S(t)Bu)23](5+) ({Ag28S23} for short)
      nanocluster with a "crab-like" shape in compound [Ag28(S(t)Bu)23](CF3COO)5.8CH3OH
      (1), which has been synthesized by the self-assembly of AgS(t)Bu with CF3COOH,
      Et3N and KBr/KI in methanol. The diffuse reflection spectrum and luminescence
      spectra of 1 were investigated.

PMID- 24921973
TI  - Role of C-C motif ligand 2 and C-C motif receptor 2 in murine pulmonary graft
      versus-host disease after lipopolysaccharide inhalations.
AB  - Environmental exposures are a potential trigger of chronic pulmonary graft-versus
      host disease (pGVHD) after successful recovery from hematopoietic cell transplant
      (HCT). We hypothesized that inhalations of LPS, a prototypic environmental
      stimulus, trigger pGVHD via increased pulmonary recruitment of donor-derived
      antigen-presenting cells (APCs) through the C-C motif ligand 2 (CCL2)-C-C motif
      receptor 2 (CCR2) chemokine axis. B10.BR(H2(k)) and C57BL/6(H2(b)) mice underwent
      allogeneic (Allo) or syngeneic (Syn) HCT with wild-type (WT) C57BL/6, CCL2(-/-),
      or CCR2(-/-) donors. After 4 weeks, recipient mice received daily inhaled LPS for
      5 days and were killed at multiple time points. Allo mice exposed to repeated
      inhaled LPS developed prominent lymphocytic bronchiolitis, similar to human
      pGVHD. The increase in pulmonary T cells in Allo mice after LPS exposures was
      accompanied by increased CCL2, CCR2, and Type-1 T-helper cytokines as well as by
      monocytes and monocyte-derived dendritic cells (moDCs) compared with Syn and
      nontransplanted controls. Using CCL2(-/-) donors leads to a significant decrease
      in lung DCs but to only mildly reduced CD4 T cells. Using CCR2(-/-) donors
      significantly reduces lung DCs and moDCs but does not change T cells. CCL2 or
      CCR2 deficiency does not alter pGVHD pathology but increases airway
      hyperreactivity and IL-5 or IL-13 cytokines. Our results show that hematopoietic
      donor-derived CCL2 and CCR2 regulate recruitment of APCs to the Allo lung after
      LPS exposure. Although they do not alter pathologic pGVHD, their absence is
      associated with increased airway hyperreactivity and IL-5 and IL-13 cytokines.
      These results suggest that the APC changes that result from CCL2-CCR2 blockade
      may have unexpected effects on T cell differentiation and physiologic outcomes in
      HCT. 

PMID- 24921976
TI  - Relationship of irritable bowel syndrome (IBS) and major depression in Mumbai,
      India *.

PMID- 24921975
TI  - Psychiatric evaluation of competency in cancer patients.
AB  - This study was conducted to investigate the profile of patients referred for
      psychiatric evaluation of competency among patients with cancer. Among the 1721
      referred cancer patients, 43 (2.5%) were referred for competency evaluation. The
      most common reason for competency evaluation was refusal of test or treatment,
      and the common psychiatric diagnoses were adjustment disorders, delirium and
      personality disorders. Cancer patients with personality disorders were more
      likely to be evaluated as competent, while patients with delirium and dementia
      were often incompetent; those with adjustment disorders, major depression and
      psychotic illness could be either competent or incompetent. While these findings
      were almost consistent with those reported from previous studies, some results
      may be unique to cancer patients. 

PMID- 24921977
TI  - Pulmonary abnormalities and carotid atherosclerosis in ex-smokers without airflow
      limitation.
AB  - It is well-established that COPD patients have a burden of vascular disease that
      cannot be fully-explained by smoking history but the mechanistic links between
      atherosclerosis and pulmonary disease in COPD patients are not well-understood.
      Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical
      pulmonary and vascular disease, although potentially present, has not been
      described or evaluated. Hence our aim was to use sensitive three-dimensional (3D)
      pulmonary and carotid imaging to quantify pulmonary airway/parenchyma
      abnormalities and atherosclerosis in ex-smokers without airflow limitation or
      symptoms consistent with COPD. We evaluated 61 subjects without airflow
      limitation including 34 never- (72 +/- 6 years) and 27 ex-smokers (73 +/- 9
      years), who provided written informed consent to spirometry, plethysmography,
      (3)He magnetic resonance imaging (MRI) and carotid ultrasound (US) and, for ex
      smokers alone, thoracic X-ray computed tomography (CT). Ex-smokers had
      significantly greater (3)He ventilation defect percent (VDP = 7%, p = 0.001) and
      carotid total plaque volume (TPV = 250 mm(3), p = 0.002) than never-smokers,
      although there were no significant differences for spirometry or plethysmography,
      and CT airway and emphysema measurements were normal. There were univariate
      relationships for (3)He VDP with carotid intima media thickness (IMT, r = 0.42, p
      = 0.004), TPV (r = 0.41, p = 0.006) and vessel wall volume (VWV, r = 0.40, p =
      0.007). Multivariate models that included age, BMI, FEV1, DLCO and VDP showed
      that only VDP significantly predicted IMT (beta = 0.41, p = 0.001), VWV (beta =
      0.45, p = 0.003) and TPV (beta = 0.38, p = 0.005). In summary, there was imaging
      evidence of mild airways disease and carotid plaque burden that were related and
      significantly greater in ex-smokers without airflow limitation than in never
      smokers.

PMID- 24921978
TI  - Diazaquinomycins E-G, novel diaza-anthracene analogs from a marine-derived
      Streptomyces sp.
AB  - As part of our program to identify novel secondary metabolites that target drug
      resistant ovarian cancers, a screening of our aquatic-derived actinomycete
      fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5)
      led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E
      (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and
      diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The
      structures of DAQF and DAQG were solved through deconvolution of X-Ray
      diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited
      moderate LC50 values against OVCAR5 of 9.0 and 8.8 MUM, respectively. At lethal
      concentrations of DAQA, evidence of DNA damage was observed via induction of
      apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure
      elucidation, and biological activity of these secondary metabolites. 

PMID- 24921979
TI  - Link between domoic acid production and cell physiology after exchange of
      bacterial communities between toxic Pseudo-nitzschia multiseries and non-toxic
      Pseudo-nitzschia delicatissima.
AB  - Bacteria are known to influence domoic acid (DA) production by Pseudo-nitzschia
      spp., but the link between DA production and physiology of diatoms requires more
      investigation. We compared a toxic P. multiseries to a non-toxic P.
      delicatissima, investigating links between DA production, physiological
      parameters, and co-occurring bacteria. Bacterial communities in cultures of both
      species were reduced by antibiotic treatment, and each of the diatoms was
      inoculated with the bacterial community of the other species. The physiology of
      P. delicatissima was minimally affected by the absence of bacteria or the
      presence of alien bacteria, and no DA was detected. P. multiseries grew faster
      without bacteria, did not produce a significant amount of DA, and exhibited
      physiological characteristics of healthy cells. When grown with alien bacteria,
      P. multiseries did not grow and produced more DA; the physiology of these cells
      was affected, with decreases in chlorophyll content and photosynthetic
      efficiency, an increase in esterase activity, and almost 50% mortality of the
      cells. The alien bacterial community had morphological and cellular
      characteristics very different from the original bacteria, and the number of free
      living bacteria per algal cell was much higher, suggesting the involvement of
      bacteria in DA production. 

PMID- 24921980
TI  - Switching from efavirenz to nevirapine in children: 1-week dose escalation
      strategy.

PMID- 24921981
TI  - Chirality sensitive binding of tryptophan enantiomers with pristine single wall
      carbon nanotubes.
AB  - We report the differential binding nature of pristine single wall carbon
      nanotubes (SWNTs) with tryptophan enantiomers. The differential co-operative
      response between the pristine SWNTs (topologically chiral) and L- and D
      tryptophan (geometrically chiral) provides the insight that geometrical chirality
      itself manifests with topological chirality in a complex way.

PMID- 24921982
TI  - Cohesive energy and line energy of graphene.
AB  - The theory presented enables calculating the cohesive energy and line energy (the
      work of formation of the unit border line length) of graphene from the first
      principles data, which also yields estimate of the line tension of graphene at
      zero temperature. Contributions from chemical bonds and dispersion forces have
      been estimated separately to give a summary value of 16.7 * 10(-10) J m(-1) for
      the line energy of graphene. The significance of line energy and line tension for
      nanotube formation is discussed. 

PMID- 24921983
TI  - Optic disc characteristics in patients with glaucoma and combined superior and
      inferior retinal nerve fiber layer defects.
AB  - IMPORTANCE: Eyes with initial bihemifield defects show faster progression
      compared with eyes with initial single-hemifield involvement, suggesting greater
      optic nerve susceptibility to glaucomatous damage. We hypothesized that certain
      disc phenotypes may exist in patients with glaucoma who have bihemispheric
      structural damage at the initial stage of the disease. OBJECTIVE: To identify the
      optic disc characteristics related to bihemispheric retinal nerve fiber layer
      (RNFL) defects in early-stage glaucoma. DESIGN, SETTING, AND PARTICIPANTS: A
      cross-sectional study of 136 patients with early-stage primary open-angle
      glaucoma from a glaucoma referral practice. Eyes were divided into those with
      RNFL defects in the superior or the inferior hemisphere (group 1) and those with
      bihemispheric RNFL defects (group 2). We measured the degree of horizontal tilt
      angle and RNFL thickness using spectral-domain optical coherence tomography. We
      performed multivariate logistic regression analysis to determine potential risk
      factors related to the bihemispheric RNFL defects. EXPOSURES: Bihemispheric RNFL
      defects. MAIN OUTCOMES AND MEASURES: Disc ovality (defined as the ratio between
      the longest and shortest diameters of the optic disc), the degree of horizontal
      tilt angle, and the presence of bihemispheric RNFL defects. Asymmetry in RNFL
      thickness between hemispheres was defined as the difference between the superior
      and inferior mean RNFL thickness. RESULTS: Disc ovality (mean [SD], 1.09 [0.12]
      in group 1 vs 1.18 [0.18] in group 2; difference, -0.09; 95% CI, -0.14 to -0.03),
      proportion of tilted discs (5.3% vs 17.5%, respectively; difference, -12.2; 95%
      CI, -13.0 to -11.4), and horizontal tilt angle (mean [SD], 4.17 degrees  [4.13
      degrees ] vs 5.93 degrees  [4.84 degrees ], respectively; difference, -1.76; 95%
      CI, -3.47 to -0.03) were significantly different between groups 1 and 2 (P =
      .001, P = .03, and P = .045, respectively). The asymmetry in RNFL thickness
      decreased with increased disc ovality (exponentiation of the B coefficient, 1.67;
      95% CI, 1.10-2.55; P = .02), although associations were not identified with
      spherical equivalent, axial length, or the angle between the temporal retinal
      veins. In multivariate logistic analysis, disc ovality was suggested to be an
      independent risk factor for bihemispheric RNFL defects, after controlling for
      mean deviation, age, axial length, and disc area (P = .02). CONCLUSIONS AND
      RELEVANCE: Optic disc tilt appears to be associated with bihemispheric RNFL
      defects in patients with early glaucoma, regardless of their refractive status.
      These data suggest that disc tilt, associated with bihemispheric structural
      damages, is a risk factor for glaucoma progression.

PMID- 24921984
TI  - Analysis of deep brain stimulation electrode characteristics for neural
      recording.
AB  - OBJECTIVE: Closed-loop deep brain stimulation (DBS) systems have the potential to
      optimize treatment of movement disorders by enabling automatic adjustment of
      stimulation parameters based on a feedback signal. Evoked compound action
      potentials (ECAPs) and local field potentials (LFPs) recorded from the DBS
      electrode may serve as suitable closed-loop control signals. The objective of
      this study was to understand better the factors that influence ECAP and LFP
      recording, including the physical presence of the electrode, the geometrical
      dimensions of the electrode, and changes in the composition of the peri-electrode
      space across recording conditions. APPROACH: Coupled volume conductor-neuron
      models were used to calculate single-unit activity as well as ECAP responses and
      LFP activity from a population of model thalamic neurons. MAIN RESULTS: Comparing
      ECAPs and LFPs measured with and without the presence of the highly conductive
      recording contacts, we found that the presence of these contacts had a negligible
      effect on the magnitude of single-unit recordings, ECAPs (7% RMS difference
      between waveforms), and LFPs (5% change in signal magnitude). Spatial averaging
      across the contact surface decreased the ECAP magnitude in a phase-dependent
      manner (74% RMS difference), resulting from a differential effect of the contact
      on the contribution from nearby or distant elements, and decreased the LFP
      magnitude (25% change). Reductions in the electrode diameter or recording contact
      length increased signal energy and increased spatial sensitivity of single neuron
      recordings. Moreover, smaller diameter electrodes (500 um) were more selective
      for recording from local cells over passing axons, with the opposite true for
      larger diameters (1500 um). Changes in electrode dimensions had phase-dependent
      effects on ECAP characteristics, and generally had small effects on the LFP
      magnitude. ECAP signal energy and LFP magnitude decreased with tighter contact
      spacing (100 um), compared to the original dimensions (1500 um), with the
      opposite effect on the ECAP at longer contact-to-contact distances (2000 um).
      Finally, acute edema reduced the single neuron and population ECAP signal energy,
      as well as LFP magnitude, and glial encapsulation had the opposite effect, after
      accounting for loss of cells in the peri-electrode space. SIGNIFICANCE: This
      study determined recording conditions and electrode designs that influence ECAP
      and LFP recording fidelity.

PMID- 24921985
TI  - Asthma control and management in 8,000 European patients: the REcognise Asthma
      and LInk to Symptoms and Experience (REALISE) survey.
AB  - BACKGROUND: Asthma is one of the most common chronic diseases in the world, and
      previous studies have reported low levels of control. Recent developments in the
      availability and use of online sources of information about asthma might add to
      patients' knowledge and help improve control. AIMS: To investigate whether asthma
      control has improved by assessing levels of symptoms, exacerbations and Global
      Initiative for Asthma-defined control in a real-life population of patients who
      use the Internet and social media, as well as evaluate patient perception of
      control and attitudes to asthma. METHODS: Online surveys were conducted among
      8,000 patients with asthma (aged 18-50 years, >=2 prescriptions in the previous 2
      years, use of social media) from 11 European countries. RESULTS: Levels of asthma
      control were low: 45% of respondents had uncontrolled asthma. Acute exacerbations
      were common: 44% of respondents reported having used oral steroids for asthma in
      the previous 12 months, 24% had visited an emergency department and 12% had been
      hospitalised. More than 80% of respondents (overall, and among those with a
      history of exacerbations) considered their asthma to be controlled. Of those who
      had an exacerbation requiring oral steroids, 75% regarded their asthma as not
      serious. CONCLUSIONS: Asthma control in Europe remains poor; symptoms and
      exacerbations are common. Many patients regard their asthma as controlled and not
      serious despite experiencing symptoms and exacerbations. There is a need to
      assess patients' control, risk and inhaler technique, and to ensure that patients
      are prescribed, and take, appropriate treatments.

PMID- 24921986
TI  - Synergistic plasmonic and photonic crystal light-trapping: architectures for
      optical up-conversion in thin-film solar cells.
AB  - We demonstrate, numerically, that with a 60 nanometer layer of optical up
      conversion material, embedded with plasmonic core-shell nano-rings and placed
      below a sub-micron silicon conical-pore photonic crystal it is possible to absorb
      sunlight well above the Lambertian limit in the 300-1100 nm range. With as little
      as 500 nm, equivalent bulk thickness of silicon, the maximum achievable photo
      current density (MAPD) is about 36 mA/cm2, using above-bandgap sunlight. This
      MAPD increases to about 38 mA/cm2 for one micron of silicon. Our architecture
      also provides solar intensity enhancement by a factor of at least 1400 at the sub
      bandgap wavelength of 1500 nm, due to plasmonic and photonic crystal resonances,
      enabling a further boost of photo-current density from up-conversion of sub
      bandgap sunlight. With an external solar concentrator, providing 100 suns, light
      intensities sufficient for significant nonlinear up-conversion can be realized.
      Two-photon absorption of sub-bandgap sunlight is further enhanced by the large
      electromagnetic density of states in the photonic crystal at the re-emission
      wavelength near 750 nm. It is suggested that this synergy of plasmonic and
      photonic crystal resonances can lead to unprecedented power conversion efficiency
      in ultra-thin-film silicon solar cells.

PMID- 24921987
TI  - Hexagonal sphere gratings for enhanced light trapping in crystalline silicon
      solar cells.
AB  - Enhanced absorption of near infrared light in silicon solar cells is important
      for achieving high conversion efficiencies while reducing the solar cell's
      thickness. Hexagonal gratings on the rear side of solar cells can achieve such
      absorption enhancement. Our wave optical simulations show photocurrent density
      gains of up to 3 mA/cm2 for solar cells with a thickness of 40 um and a planar
      front side. Hexagonal sphere gratings have been fabricated and optical
      measurements confirm the predicted absorption enhancement. The measured
      absorption enhancement corresponds to a photocurrent density gain of 1.04 mA/cm2
      for planar wafers with a thickness of 250 um and 1.49 mA/cm2 for 100 um.

PMID- 24921988
TI  - Optical absorption enhancement in 3D silicon oxide nano-sandwich type solar cell.
AB  - Recent research in the field of photovoltaic and solar cell fabrication has shown
      the potential to significantly enhance light absorption in thin-film solar cells
      by using surface texturing and nanostructure coating techniques. In this paper,
      for the first time, we propose a new method for nano sandwich type thin-film
      solar cell fabrication by combining the laser amorphization (2nd solar cell
      generation) and laser nanofibers generation (3rd solar cell generation)
      techniques. In this novel technique, the crystalline silicon is irradiated by
      megahertz frequency femtosecond laser pulses under ambient conditions and the
      multi-layer of amorphorized silicon and nano fibrous layer are generated in the
      single-step on top of the silicon substrate. Light spectroscopy results show
      significant enhancement of light absorption in the generated multi layers solar
      cells (Silicon Oxide nanofibers / thin-film amorphorized silicon). This method is
      single step and no additional materials are added and both layers of the
      amorphorized thin-film silicon and three-dimensional (3D) silicon oxide
      nanofibrous structures are grown on top of the silicon substrate after laser
      irradiation. Finally, we suggest how to maximize the light trapping and optical
      absorption of the generated nanofibers/thin-film cells by optimizing the laser
      pulse duration. 

PMID- 24921989
TI  - Photovoltaic electrical properties of aqueous grown ZnO antireflective
      nanostructure on Cu(In,Ga)Se2 thin film solar cells.
AB  - A solution-grown subwavelength antireflection coating has been investigated for
      enhancing the photovoltaic efficiency of thin film solar cells. The 100-nm-height
      ZnO nanorods coating benefited the photocurrent of Cu(In,Ga)Se2 solar cells from
      31.7 to 34.5 mA/cm2 via the decrease of surface light reflectance from 14.5% to
      7.0%, contributed by the gradual refractive index profile between air and AZO
      window layer. The further reduction of surface reflectance to 2.3% in the case of
      540-nm-height nanorods, yet, lowered the photocurrent to 29.5 mA/cm2, attributed
      to the decrease in transmittance. The absorption effect of hydrothermal grown ZnO
      nanorods was explored to optimize the antireflection function in enhancing
      photovoltaic performances.

PMID- 24921990
TI  - A sensor-less LED dimming system based on daylight harvesting with BIPV systems.
AB  - Artificial lighting in office buildings typically requires 30% of the total
      energy consumption of the building, providing a substantial opportunity for
      energy savings. To reduce the energy consumed by indoor lighting, we propose a
      sensor-less light-emitting diode (LED) dimming system using daylight harvesting.
      In this study, we used light simulation software to quantify and visualize
      daylight, and analyzed the correlation between photovoltaic (PV) power generation
      and indoor illumination in an office with an integrated PV system. In addition,
      we calculated the distribution of daylight illumination into the office and
      dimming ratios for the individual control of LED lights. Also, we were able
      directly to use the electric power generated by PV system. As a result, power
      consumption for electric lighting was reduced by 40 - 70% depending on the season
      and the weather conditions. Thus, the dimming system proposed in this study can
      be used to control electric lighting to reduce energy use cost-effectively and
      simply. 

PMID- 24921991
TI  - Design of wide-angle selective absorbers/emitters with dielectric filled metallic
      photonic crystals for energy applications.
AB  - The design and simulation of a wide angle, spectrally selective absorber/emitter
      metallic photonic crystal (MPhC) is presented. By using dielectric filled
      cavities, the angular, spectrally selective absorption/emission of the MPhC is
      dramatically enhanced over an air filled design by minimizing diffraction losses.
      Theoretical analysis is performed and verified via rigorous coupled wave analysis
      (RCWA) based simulations. An efficiency comparison of the dielectric filled
      designs for solar thermophotovoltaic applications is performed for the absorber
      and emitter which yields a 7% and 15.7% efficiency improvement, respectively,
      compared to air filled designs. The converted power output density is also
      improved by 33.5%. 

PMID- 24921992
TI  - Enhancements of the emission and light extraction of a radiating dipole coupled
      with localized surface plasmon induced on a surface metal nanoparticle in a light
      emitting device.
AB  - The radiated power enhancement and more congregated radiation of a radiating
      dipole within a GaN material when it is coupled with the localized surface
      plasmon (LSP) resonance modes induced on a surface Ag nanoparticle (NP) are
      numerically demonstrated. The numerical study is based on an algorithm including
      the induction of LSP resonance on the Ag NP by the source dipole and the feedback
      effect of the LSP resonance field on the source dipole behavior. The spectral
      peaks of radiated power enhancement correspond to the substrate LSP resonance
      modes with mode fields mainly distributed around the bottom of the Ag NP such
      that the coupling system radiates mainly into the GaN half-space. By moving the
      radiating dipole laterally away from the bottom of the Ag NP, the spectral peaks
      of radiated power enhancement red shift and their levels diminish with increasing
      lateral distance. The radiation patterns in the GaN half-space show more
      congregated radiation around the vertical direction, indicating that the light
      extraction efficiency can be enhanced in an LSP-coupled light-emitting device
      with surface metal NPs. 

PMID- 24921993
TI  - Suppressing lossy-film-induced angular mismatches between reflectance and
      transmittance extrema: optimum optical designs of interlayers and AR coating for
      maximum transmittance into active layers of CIGS solar cells.
AB  - The investigation of optimum optical designs of interlayers and antireflection
      (AR) coating for achieving maximum average transmittance (T(ave)) into the CuIn(1
      x)Ga(x)Se2 (CIGS) absorber of a typical CIGS solar cell through the suppression
      of lossy-film-induced angular mismatches is described. Simulated-annealing
      algorithm incorporated with rigorous electromagnetic transmission-line network
      approach is applied with criteria of minimum average reflectance (R(ave)) from
      the cell surface or maximum T(ave) into the CIGS absorber. In the presence of one
      MgF2 coating, difference in R(ave) associated with optimum designs based upon the
      two distinct criteria is only 0.3% under broadband and nearly omnidirectional
      incidence; however, their corresponding T(ave) values could be up to 14.34%
      apart. Significant T(ave) improvements associated with the maximum-T(ave)-based
      design are found mainly in the mid to longer wavelengths and are attributed to
      the largest suppression of lossy-film-induced angular mismatches over the entire
      CIGS absorption spectrum. Maximum-T(ave)-based designs with a MgF2 coating
      optimized under extreme deficiency of angular information is shown, as opposed to
      their minimum-R(ave)-based counterparts, to be highly robust to omnidirectional
      incidence.

PMID- 24921994
TI  - Performance of GaN-based light-emitting diodes fabricated using GaN epilayers
      grown on silicon substrates.
AB  - Light extraction of GaN-based light-emitting diodes grown on Si(111) substrate
      (GaN-on-Si based LEDs) is presented in this study. Three different designs of GaN
      on-Si based LEDs with the lateral structure, lateral structure on mirror/Si(100)
      substrate, and vertical structure on mirror/Si(100) substrate were epitaxially
      grown by metalorganic chemical vapor deposition and fabricated using chemical
      lift-off and double-transfer techniques. Current-voltage, light output power, far
      field radiation patterns, and electroluminescence characteristics of these three
      LEDs were discussed. At an injection current of 700 mA, the output powers of LEDs
      with the lateral structure on mirror/Si(100) substrate and vertical structure on
      mirror/Si(100) substrate were measured to be 155.07 and 261.07 mW, respectively.
      The output powers of these two LEDs had 70.63% and 187.26% enhancement compared
      to that of LED with the lateral structure, respectively. The result indicated
      this vertical structure LED was useful in improving the light extraction due to
      an enhancement in light scattering efficiency while the high-reflection mirror
      and diffuse surfaces were employed. 

PMID- 24921995
TI  - Index-matched IWKB method for the measurement of spatially varying refractive
      index profiles within thin-film photovoltaics.
AB  - In many thin-film photovoltaic devices, the photoactive layer has a spatially
      varying refractive index in the substrate-normal direction, but measurement of
      this variation with high spatial resolution is difficult due to the thinness of
      these layers (typically 200 nm for organic photovoltaics). We demonstrate a new
      method for reconstructing the depth-dependent refractive-index profile with high
      spatial resolution (~10 nm at a wavelength of 500 nm) in thin (200 nm)
      photoactive layers by depositing a relatively thick index-matched layer (1-10
      MUm) adjacent to the photoactive layer and applying the Inverse Wentzel-Kramers
      Brillouin (IWKB) method. This novel technique, which we refer to as index-matched
      IWKB (IM-IWKB), is applicable to any thin film, including the photoactive layers
      of a broad range of thin-film photovoltaics. 

PMID- 24921996
TI  - Photoelectrochemical activity on Ga-polar and N-polar GaN surfaces for energy
      conversion.
AB  - Hydrogen generation through direct photoelectrolysis of water was studied using
      photoelectrochemical cells made of different facets of free-standing polar GaN
      system. To build the fundamental understanding at the differences of surface
      photochemistry afforded by the GaN {0001}and {000-1}polar surfaces, we correlated
      the relationship between the surface structure and photoelectrochemical
      performance on the different polar facets. The photoelectrochemical measurements
      clearly revealed that the Ga-polar surface had a more negative onset potential
      relative to the N-polar surface due to the much negative flat-band potential. At
      more positive applied voltages, however, the N-polar surface yielded much higher
      photocurrent with conversion efficiency of 0.61% compared to that of 0.55% by
      using the Ga-polar surface. The reason could be attributed to the variation in
      the band structure of the different polar facets via Mott-Schottky analyses.
      Based on this work, understanding the facet effect on photoelectrochemical
      activity can provide a blueprint for the design of materials in solar hydrogen
      applications. 

PMID- 24921997
TI  - Experimental measurements of a prototype high concentration Fresnel lens CPV
      module for the harvesting of diffuse solar radiation.
AB  - A prototype concentrator photovoltaic (CPV) module with high solar concentration,
      an added low-cost solar cell, and an adjoining multi-junction solar cell is
      fabricated and experimentally demonstrated. In the present CPV module, the low
      cost solar cell captures diffuse solar radiation penetrating the concentrator
      lens and the multi-junction cell captures concentrated direct solar radiation. On
      sun test results show that the electricity generated by a Fresnel lens-based CPV
      module with an additional crystalline silicon solar cell is greater than that for
      a conventional CPV module by a factor of 1.44 when the mean ratio of diffuse
      normal irradiation to global normal irradiation at the module aperture is 0.4.
      Several fundamental optical characteristics are presented for the present module.

PMID- 24921998
TI  - Monte Carlo study of PbSe quantum dots as the fluorescent material in luminescent
      solar concentrators.
AB  - In this paper, Monte Carlo simulations were performed to determine the potential
      efficiencies of luminescent solar concentrator (LSC) systems using PbSe quantum
      dots (QDs) as the active fluorescent material. The simulation results suggest
      that PbSe QD LSCs display good absorption characteristics, but yield limited LSC
      power conversion efficiency due to self-absorption and down-conversion loss. It
      is proposed that the self-absorption loss can be reduced by utilizing Forster
      resonance energy transfer between two different sizes of PbSe QDs, yielding
      pronounced improvement in the optical efficiency of LSCs. 

PMID- 24921999
TI  - Laser-induced plasma generation and evolution in a transient spray.
AB  - The behaviors of laser-induced plasma and fuel spray were investigated by
      visualizing images with an ultra-high-speed camera. Time-series images of laser
      induced plasma in a transient spray were visualized using a high-speed color
      camera. The effects of a shockwave generated from the laser-induced plasma on the
      evaporated spray behavior were investigated. The interaction between a single
      droplet and the laser-induced plasma was investigated using a single droplet
      levitated by an ultrasonic levitator. Two main conclusions were drawn from these
      experiments: (1) the fuel droplets in the spray were dispersed by the shockwave
      generated from the laser-induced plasma; and (2) the plasma position may have
      shifted due to breakdown of the droplet surface and the lens effect of droplets. 

PMID- 24922000
TI  - Analytical solution for haze values of aluminium-induced texture (AIT) glass
      superstrates for a-Si:H solar cells.
AB  - Light scattering at randomly textured interfaces is essential to improve the
      absorption of thin-film silicon solar cells. Aluminium-induced texture (AIT)
      glass provides suitable scattering for amorphous silicon (a-Si:H) solar cells.
      The scattering properties of textured surfaces are usually characterised by two
      properties: the angularly resolved intensity distribution and the haze. However,
      we find that the commonly used haze equations cannot accurately describe the
      experimentally observed spectral dependence of the haze of AIT glass. This is
      particularly the case for surface morphologies with a large rms roughness and
      small lateral feature sizes. In this paper we present an improved method for haze
      calculation, based on the power spectral density (PSD) function of the randomly
      textured surface. To better reproduce the measured haze characteristics, we
      suggest two improvements: i) inclusion of the average lateral feature size of the
      textured surface into the haze calculation, and ii) considering the opening angle
      of the haze measurement. We show that with these two improvements an accurate
      prediction of the haze of AIT glass is possible. Furthermore, we use the new
      equation to define optimum morphology parameters for AIT glass to be used for a
      Si:H solar cell applications. The autocorrelation length is identified as the
      critical parameter. For the investigated a-Si:H solar cells, the optimum
      autocorrelation length is shown to be 320 nm. 

PMID- 24922001
TI  - Investigation of optical absorptance of one-dimensionally periodic silicon
      gratings as solar absorbers for solar cells.
AB  - A rigorous design using periodic silicon (Si) gratings as absorbers for solar
      cells in visible and near-infrared regions is numerically presented. The
      structure consists of a subwavelength Si grating layer on top of an Si substrate.
      Ranges of grating dimensions are preliminary considered satisfying simple and
      feasible fabrication techniques with an aspect ratio defined as the ratio of the
      grating thickness (d) and the grating lamella width (w), with 0 < d/w < 1.0. The
      subwavelength grating structure (SGS) is assumed to comprise different lamella
      widths and slits within each period in order to finely tune the grating profile
      such that the absorptance is significantly enhanced in the whole wavelength
      region. The results showed that the compound SGS yields an average absorptance of
      0.92 which is 1.5 larger than that of the Si plain and conventional grating
      structures. It is shown that the absorptance spectrum of the proposed SGS is
      insensitive to the angle of incidence of the incoming light. The absorptance
      enhancement is also investigated by computing magnetic field, energy density, and
      Poynting vector distributions. The results presented in this study show that the
      proposed method based on nanofabrication techniques provides a simple and
      promising solution to design solar energy absorbers or other energy harvesting
      devices. 

PMID- 24922002
TI  - Photovoltaic effect in multiphase Bi-Mn-O thin films.
AB  - We report an external solar power conversion efficiency of ~0.1% in Bi-Mn-O thin
      films grown onto (111) oriented Niobium doped SrTiO3 (STO) single crystal
      substrate by pulse laser deposition (PLD). The films contain BiMnO3 (BMO) and
      Mn3O4 (MO) phases, which both grow epitaxially. The growth conditions were
      tailored to obtain films with different Bi/Mn ratios. The films were subsequently
      illuminated under a sun simulator (AM 1.5 G). We find that the Bi/Mn ratio in the
      film affects the magnitude of the photo induced voltage and photocurrent and
      therefore the photovoltaic conversion efficiency. Specifically, a higher Bi/Mn
      ratio (towards unity) in the film increases the power conversion efficiency. This
      effect is described in terms of a more favorable energy band alignment of the
      film/substrate hetero-structure junction, which controls photo carrier
      separation.

PMID- 24922003
TI  - Breakdown plasma and vortex flow control for laser ignition using a combination
      of nano- and femto-second lasers.
AB  - The breakdown plasma and successive flow leading to combustion are controlled by
      the combination of a nano-second Nd:YAG laser and a femto-second Ti:Sapphire
      (TiS) laser. The behaviors are captured by an intensified charged coupled device
      (ICCD) camera and a high-speed schlieren optical system. The TiS laser determines
      the initial position of the breakdown by supplying the initial electrons in the
      optical axis of focusing YAG laser pulses. We show that the initial position of
      the breakdown can be controlled by the incident position of the TiS laser. In
      addition, the ignition lean limit of the flammable mixture changes depending on
      the TiS laser incident position, which is influenced by hot gas distribution and
      the flow in the flame kernel. 

PMID- 24922004
TI  - Optimization of generalized dielectric nanostructures for enhanced light trapping
      in thin-film photovoltaics via boosting the local density of optical states.
AB  - Recent work has shown that using a high-index cladding atop a lower-index
      photovoltaic absorber enables absorption of light beyond the ergodic (4n2) limit.
      In this paper, we propose a generalized optimization method for deriving optimal
      geometries that allow for such enhancement. Specifically, we adapted the direct
      binary-search algorithm to optimize a complex 2-D multi-layer structure with the
      explicit goal of increasing photocurrent. We show that such an optimization
      results in enhancing the local density of optical states in an ultra-thin
      absorber, which forms a slot-waveguide geometry in the presence of a higher-index
      overcladding. Numerical simulations confirmed optical absorption approaching 100%
      and absorption-enhancement beyond the ergodic (4n2) limit for specific spectral
      bands of interest. Our method provides a direct, intuitive and computationally
      scalable approach for designing light-trapping nanostructures.

PMID- 24922005
TI  - Antitumor efficacy of the anti-interleukin-6 (IL-6) antibody siltuximab in mouse
      xenograft models of lung cancer.
AB  - INTRODUCTION: Interleukin-6 (IL-6) can activate downstream signaling pathways in
      lung cancer cells, such as the STAT3 pathway, and is reported to be produced by
      tumor cells with activating EGFR mutations. We examined IL-6/STAT3 in lung cancer
      tumor tissues and the effects of siltuximab, a neutralizing antibody to human IL
      6, in mouse models of lung cancer. METHODS: IL-6 and STAT3 activation levels were
      compared with tumor histology and presence of KRAS mutations in snap-frozen, non
      small-cell lung cancer tumors. The effects of siltuximab alone or in combination
      with erlotinib were examined in mouse xenograft models constructed using three
      cell line xenograft models and one primary explant mouse model. We examined the
      influence of cancer-associated fibroblasts (CAFs) on tumor growth and siltuximab
      effects. RESULTS: IL-6 levels were higher in tumors of squamous cell versus
      adenocarcinoma histology and were not associated with presence of KRAS mutations.
      Tyrosine phosphorylation status of STAT3 did not correlate with tumor IL-6
      levels. Serine phosphorylation of STAT3 was correlated with KRAS mutation status.
      Both tumor and stromal cells contributed to total IL-6 within tumors. Siltuximab
      had minimal effect as a single agent in xenografts with tumor cells alone;
      however, in models coadministered with CAFs, siltuximab had more potent effects
      on tumor inhibition. We observed no effects of combined erlotinib and siltuximab.
      CONCLUSIONS: IL-6 is elevated in subsets of human NSCLCs, especially with
      squamous cell histology. Tumors supported by stromal production of IL-6 seem to
      be the most vulnerable to tumor growth inhibition by siltuximab.

PMID- 24922006
TI  - A high content clonogenic survival drug screen identifies mek inhibitors as
      potent radiation sensitizers for KRAS mutant non-small-cell lung cancer.
AB  - INTRODUCTION: Traditional clonogenic survival and high throughput colorimetric
      assays are inadequate as drug screens to identify novel radiation sensitizers. We
      developed a method that we call the high content clonogenic survival assay (HCSA)
      that will allow screening of drug libraries to identify candidate radiation
      sensitizers. METHODS: Drug screen using HCSA was done in 96 well plates. After
      drug treatment, irradiation, and incubation, colonies were stained with crystal
      violet and imaged on the INCell 6000 (GE Health). Colonies achieving 50 or more
      cells were enumerated using the INCell Developer image analysis software. A proof
      of-principle screen was done on the KRAS mutant lung cancer cell line H460 and a
      Custom Clinical Collection (146 compounds). RESULTS: Multiple drugs of the same
      class were found to be radiation sensitizers and levels of potency seemed to
      reflect the clinical relevance of these drugs. For instance, several PARP
      inhibitors were identified as good radiation sensitizers in the HCSA screen.
      However, there were also a few PARP inhibitors not found to be sensitizing that
      have either not made it into clinical development, or in the case of BSI-201, was
      proven to not even be a PARP inhibitor. We discovered that inhibitors of pathways
      downstream of activated mutant KRAS (PI3K, AKT, mTOR, and MEK1/2) sensitized H460
      cells to radiation. Furthermore, the potent MEK1/2 inhibitor tramenitib
      selectively enhanced radiation effects in KRAS mutant but not wild-type lung
      cancer cells. CONCLUSIONS: Drug screening for novel radiation sensitizers is
      feasible using the HCSA approach. This is an enabling technology that will help
      accelerate the discovery of novel radiosensitizers for clinical testing.

PMID- 24922007
TI  - Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and
      pemetrexed in malignant pleural mesothelioma.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive, currently
      incurable tumor with increasing incidence in industrialized countries. Tumor
      necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF
      family, which induces cancer cell death through extrinsic apoptotic pathway,
      while sparing normal cells. The aim of this study was to investigate the
      antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination
      with chemotherapy in MPM in vitro and in vivo. METHODS: In the present studies,
      we employed a panel of MPM cell lines to test the antitumor activity of
      recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed
      (CP) in vitro and SCID mice. RESULTS: Results demonstrated a significant increase
      of apoptosis in cell lines treated with CPT compared with those receiving CP or T
      as single agents. This synergistic effect was dependent on the ability of CP to
      increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The
      CPT combination was also effective in blocking the growth of MPM cell lines in a
      SCID mice preclinical model. CONCLUSIONS: CPT increases MPM cell death in vitro
      and in vivo compared with CP. In vitro results suggest that chemotherapy
      sensitizes MPM to TRAIL-dependent apoptosis through p53 activation and subsequent
      upregulation of DRs.

PMID- 24922008
TI  - Diagnostic performance of low-dose computed tomography screening for lung cancer
      over five years.
AB  - INTRODUCTION: Low-dose computed tomography (LD-CT) screening can reduce lung
      cancer mortality; however, it is essential to improve nodule management
      protocols. We analyze the performance of the diagnostic protocol of the
      Continuous Observation of SMOking Subjects single-center screening study, after
      long-term follow-up. METHODS: Between 2004 and 2005, 5203 asymptomatic high-risk
      individuals (>=20 pack-years, aged 50 years or older) were enrolled to undergo
      annual LD-CT for 5 years. Nodules 5 mm or smaller underwent repeat LD-CT a year
      later. Nodules larger than 5.0 mm and 8.0 mm or smaller received LD-CT 3 to 6
      months later. Nodules larger than 8.0 mm or growing underwent CT-positron
      emission tomography. True positives were any stage prevalent lung cancer,
      progressing nodules diagnosed at stage 1, localized multifocal cancer, or new
      nodules diagnosed at any stage. False negatives were progressing nodules
      diagnosed at stage >1. False positives were benign nodules resected surgically.
      RESULTS: Compliance was 79% over 5 years; 175 primary lung cancers were detected
      (0.76% per year), 136 (77.7%) were N0M0 and three were interval cancers. Eleven
      second primary lung cancers were diagnosed. Resectability was 87.4%;
      postoperative mortality 0.6%. Recall was 6.4% overall, 10.1% at baseline. False
      negatives were 14 of 175 (8%). Protocol sensitivity was 158 of 175 (90%);
      specificity 4994 of 5028 (99.4%); positive predictive value was 158 of 187
      (84.5%); and negative predictive value was 4994 of 5016 (99.7%). Twenty-nine of
      204 (14.2%) benign lesions were diagnosed surgically. Five-year overall and
      cancer-specific survival were 78% (95% confidence interval, 72-84) and 82% (95%
      confidence interval, 76%-88%) respectively. CONCLUSIONS: The performance of the
      CT protocol was satisfactory with an acceptable number of benign lesions biopsied
      surgically, low recall rate, and good oncological outcomes. However, interval and
      advanced cancers, and misdiagnoses, need to be reduced, perhaps by risk modeling
      and use of serum markers.

PMID- 24922009
TI  - Sample features associated with success rates in population-based EGFR mutation
      testing.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) mutation testing has become
      critical in the treatment of patients with advanced non-small-cell lung cancer.
      This study involves a large cohort and epidemiologically unselected series of
      EGFR mutation testing for patients with nonsquamous non-small-cell lung cancer in
      a North American population to determine sample-related factors that influence
      success in clinical EGFR testing. METHODS: Data from consecutive cases of
      Canadian province-wide testing at a centralized diagnostic laboratory for a 24
      month period were reviewed. Samples were tested for exon-19 deletion and exon-21
      L858R mutations using a validated polymerase chain reaction method with 1% to 5%
      detection sensitivity. RESULTS: From 2651 samples submitted, 2404 samples were
      tested with 2293 samples eligible for analysis (1780 histology and 513 cytology
      specimens). The overall test-failure rate was 5.4% with overall mutation rate of
      20.6%. No significant differences in the failure rate, mutation rate, or mutation
      type were found between histology and cytology samples. Although tumor
      cellularity was significantly associated with test-success or mutation rates in
      histology and cytology specimens, respectively, mutations could be detected in
      all specimen types. Significant rates of EGFR mutation were detected in cases
      with thyroid transcription factor (TTF)-1-negative immunohistochemistry (6.7%)
      and mucinous component (9.0%). CONCLUSIONS: EGFR mutation testing should be
      attempted in any specimen, whether histologic or cytologic. Samples should not be
      excluded from testing based on TTF-1 status or histologic features. Pathologists
      should report the amount of available tumor for testing. However, suboptimal
      samples with a negative EGFR mutation result should be considered for repeat
      testing with an alternate sample.

PMID- 24922010
TI  - Combined analysis of V20, VS5, pulmonary fibrosis score on baseline computed
      tomography, and patient age improves prediction of severe radiation pneumonitis
      after concurrent chemoradiotherapy for locally advanced non-small-cell lung
      cancer.
AB  - INTRODUCTION: We aimed to develop a more accurate model for predicting severe
      radiation pneumonitis (RP) after concurrent chemoradiotherapy for non-small-cell
      lung cancer. METHODS: We retrospectively analyzed data from 122 patients with
      locally advanced non-small-cell lung cancer treated with concurrent
      chemoradiotherapy. Several dose-volume histogram metrics including absolute lung
      volume spared from a 5 Gy dose (VS5) were analyzed for an association with RP
      above NCI-CTC grade 3 (RP >= G3). Clinical factors including pulmonary fibrosis
      score (PFS) and pulmonary emphysema score on baseline chest computed tomography
      (CT) were also analyzed. RESULTS: Fourteen patients (11.4%) developed RP greater
      than or equal to G3. On univariate analysis, all dose-volume histogram metrics,
      sex, and PFS on baseline CT were significantly (p < 0.05) associated with
      occurrence of RP greater than or equal to G3. Multivariate analysis revealed that
      V20 greater than or equal to 26%, VS5 less than 1500 cc, age greater than or
      equal to 68 years, and PFS on baseline CT greater than or equal to 2 were
      significant risk factors. Thus, we defined a new predictive risk score (PRS) that
      combines these factors. The cumulative incidence of RP greater than or equal to
      G3 at 12 months were 0%, 7.8%, 26.6%, and 71.4% when the PRS was 0, 3-5, 6-8, and
      9-14, respectively (p < 0.001). This PRS was superior at predicting RP than both
      V20 and VS5 combined, or V20 alone by receiver operating characteristic analysis
      (area under the curve, 0.888 versus 0.779 versus 0.678). CONCLUSIONS: V20, VS5,
      age, and PFS on baseline CT are independent and significant risk factors for
      occurrence of severe RP. Combining these factors may improve the predictability
      of severe RP.

PMID- 24922011
TI  - Patient-centered outcomes among lung cancer screening recipients with computed
      tomography: a systematic review.
AB  - INTRODUCTION: Lung cancer screening using low-dose computed tomography (LDCT) is
      now widely recommended for adults who are current or former heavy smokers. It is
      important to evaluate the impact of screening on patient-centered outcomes. Among
      current and former smokers eligible for lung cancer screening, we sought to
      determine the consequences of screening with LDCT, and subsequent results, on
      patient-centered outcomes such as quality of life, distress, and anxiety.
      METHODS: We searched the Cochrane Central Register of Controlled Trials and
      Cochrane Database of Systematic Reviews (through the fourth Quarter 2012),
      MEDLINE (2000 to May 31, 2013), reference lists of articles, and Scopus for
      relevant English-language studies and systematic reviews. To evaluate the effect
      of LDCT screening on patient-centered outcomes, we included only randomized
      controlled trials (RCTs) involving asymptomatic adults. To evaluate the
      association of particular results and/or recommendations from a screening LDCT
      with patient-centered outcomes, we included results from RCTs as well as from
      cohort studies. RESULTS: A total of 8215 abstracts were reviewed. Five
      publications from two European RCTs and one publication from a cohort study
      conducted in the United States met inclusion criteria. The process of LDCT lung
      cancer screening was associated with short-term psychologic discomfort in many
      people but did not affect distress, worry, or health-related quality of life.
      False-positive results were associated with short-term increases in distress that
      returned to levels that were similar to those among people with negative results.
      Negative results were associated with short-term decreases in distress.
      CONCLUSIONS: As lung cancer screening is implemented in the general population,
      it will be important to evaluate its association with patient-centered outcomes.
      People considering lung cancer screening should be aware of the possibility of
      distress caused by false-positive results. Clinicians may want to consider
      tailoring communication strategies that can decrease the distress associated with
      these results.

PMID- 24922012
TI  - Probing microstructural information of anisotropic scattering media using
      rotation-independent polarization parameters.
AB  - Polarization parameters contain rich information on the micro- and macro
      structure of scattering media. However, many of these parameters are sensitive to
      the spatial orientation of anisotropic media, and may not effectively reveal the
      microstructural information. In this paper, we take polarization images of
      different textile samples at different azimuth angles. The results demonstrate
      that the rotation insensitive polarization parameters from rotating linear
      polarization imaging and Mueller matrix transformation methods can be used to
      distinguish the characteristic features of different textile samples. Further
      examinations using both experiments and Monte Carlo simulations reveal that the
      residue rotation dependence in these polarization parameters is due to the
      oblique incidence illumination. This study shows that such rotation independent
      parameters are potentially capable of quantitatively classifying anisotropic
      samples, such as textiles or biological tissues. 

PMID- 24922013
TI  - Encrypted imaging based on algebraic implementation of double random phase
      encoding.
AB  - The security of important information captured by sensors and cameras is
      currently a growing concern as information theft via techniques such as side
      channel attacks become increasingly more prevalent. Double random phase encoding
      (DRPE) is an optical encryption method based on optical Fourier transform that is
      currently being used to implement secure coherent optical systems. In this paper,
      we propose a new DRPE implementation for incoherent optical systems based on
      integral photography that can be applied to "encrypted imaging (EI)" to optically
      encrypt an image before it is captured by an image sensor. Because the proposed
      incoherent DRPE is constituted from conventional DRPE by rewriting the optical
      encryption via discretization and Euler's formula, its security level is the same
      as that of conventional DRPE. The results of an experiment in which we encrypted
      a plaintext image optically and then decrypted it numerically demonstrate that
      our proposed incoherent optical security system is feasible. 

PMID- 24922014
TI  - Aerosols in coastal and inland areas in the equatorial African belt.
AB  - Aerosols affect the climate directly through absorption and reflection of
      sunlight back to space and indirectly by acting as cloud condensation nuclei.
      This paper is based on more than three decades of satellite data (1979-1994 and
      1996-2012) from total ozone mapping spectrometer (TOMS) and ozone monitoring
      instrument (OMI), which have provided measurements of backscattered radiances in
      the wavelength range from 331 to 380 nm. These data have been used to determine
      the aerosol climatology and to investigate the influence of the aerosol index
      (AI) on the ultraviolet index (UVI) in coastal land areas in Serrekunda (13.28
      degrees N, 16.34 degrees W), The Gambia, and Dar-es-Salaam (6.8 degrees S, 39.26
      degrees E), Tanzania, as well as in inland areas in Kampala (0.19 degrees N,
      32.34 degrees E), Uganda. Heavy aerosol loadings were found to occur in the dry
      seasons at all three locations. To reduce the influence of clouds, we disregarded
      TOMS and OMI data for days during which the UV reflectivity was larger than 9%
      and investigated the correlation of the AI with the UVI for the remaining days at
      the three locations. We found a high correlation coefficient of 0.82 for
      Serrekunda, but poor correlation for Kampala and Dar-es-Salaam. The average AI
      for Serrekunda was found to be about three times higher than that for Kampala or
      Dar-es-Salaam, and a positive trend was found for the AI in Kampala and Dar-es
      Salaam, whereas a negative trend was found for the AI in Serrekunda. 

PMID- 24922015
TI  - itom: an open source metrology, automation, and data evaluation software.
AB  - Modern optical sensors and measurement systems usually are a powerful combination
      of optical elements, active hardware components like actuators or sensing devices
      as well as a sophisticated control software and data evaluation algorithms. In
      order to develop and operate such systems, it is necessary to have a flexible,
      intuitive, and fast underlying software framework that also allows for rapid
      prototyping of a sensor in a dynamic lab environment. This software must be able
      to control and communicate with all necessary hardware devices and has to provide
      all the highly performant evaluation, data, and image processing algorithms
      required. In this publication, we want to present the open source measurement and
      data evaluation software suite itom, which has been designed considering the
      denoted requirements and whose development began in 2011. 

PMID- 24922016
TI  - Fabry-Perot-based Fourier-transform hyperspectral imaging allows multi-labeled
      fluorescence analysis.
AB  - We demonstrate the ability of our hyperspectral imaging device, based on a
      scanning Fabry-Perot interferometer, to obtain a single hyper-image of a sample
      marked with different fluorescent molecules, and to unambiguously discriminate
      them by observing their spectral fingerprints. An experiment carried out with
      cyanines, fluorescein, and quantum dots emitting in the yellow-orange region,
      demonstrates the feasibility of multi-labeled fluorescence microscopy without the
      use of multiple filter sets or dispersive means. 

PMID- 24922017
TI  - Optimization of fixture layouts of glass laser optics using multiple kernel
      regression.
AB  - We aim to build an integrated fixturing model to describe the structural
      properties and thermal properties of the support frame of glass laser optics.
      Therefore, (a) a near global optimal set of clamps can be computed to minimize
      the surface shape error of the glass laser optic based on the proposed model, and
      (b) a desired surface shape error can be obtained by adjusting the clamping
      forces under various environmental temperatures based on the model. To construct
      the model, we develop a new multiple kernel learning method and call it multiple
      kernel support vector functional regression. The proposed method uses two layer
      regressions to group and order the data sources by the weights of the kernels and
      the factors of the layers. Because of that, the influences of the clamps and the
      temperature can be evaluated by grouping them into different layers. 

PMID- 24922018
TI  - Mode-locked fiber lasers based on doped fiber arrays.
AB  - We designed a new kind of mode-locked fiber laser based on fiber arrays, where
      the central core is doped. A theoretical model is given for an all-fiber self
      starting mode-locked laser based on this kind of doped fiber array. Two different
      kinds of fiber lasers with negative dispersion and positive dispersion are
      simulated and discussed. The stable mode-locked pulses are generated from initial
      noise conditions by the realistic parameters. The process of self-starting mode
      locking multipulse transition and the relationship between the energy of the
      central core and the propagation distance of the pulses are discussed. Finally,
      we analyze the difference between the averaged mode-locked laser and the discrete
      mode-locked laser. 

PMID- 24922019
TI  - Temperature dependence of laser-induced micro/nanostructures for femtosecond
      laser irradiation of silicon.
AB  - The temperature dependence (from 25 degrees C to 350 degrees C) of laser-induced
      micro/nanostructures for multiple linearly polarized femtosecond laser pulse
      (pulse duration tau=35  fs, wavelength lambda=800  nm) irradiation of silicon in
      air is studied experimentally. Distinct micro/nanostructures are fabricated at
      elevated temperature. Low spatial frequency, laser-induced periodic ripple
      structures (LSFL), which are perpendicular to the polarization of the laser beam,
      are formed at all temperatures. Micrometer-size grooves, which are oriented
      perpendicular to the LSFL ripples, have been observed in the central part of the
      irradiated area above 150 degrees C. The threshold to fabricate the LSFL ripples
      goes from 1.65 to 2  kJ/m2 while the temperature of the substrate increases from
      25 degrees C to 350 degrees C. The possible mechanism of the temperature
      dependence of the micro/nanostructure generation is also discussed. These results
      demonstrate that temperature is an important parameter to be tuned to tailor the
      micro/nanostructure fabrication.

PMID- 24922020
TI  - Performance analysis of pupil-matching optical differential receivers in space-to
      ground laser communication.
AB  - In the paper, the principle and structure of a pupil-matching optical
      differential receiver consisting of double 4f confocal lens groups is introduced
      to overcome atmosphere turbulences in space-to-ground laser communication. Using
      the scalar diffraction theory, a systematic analysis of 4f lens groups is
      formulated mathematically. Based on Seidel aberration, lens aberrations produced
      by the inherent unideal lens and mutual alignment errors of double 4f lens groups
      primarily caused by relative axial displacement of the foci and vertical position
      change of the optical axes are studied mathematically and detailed. Under the
      effects of varying aberrations on the double 4f lens groups, we evaluate the
      performance of this receiving system by the model of power penalty for a given
      10(-9) bit error ratio. Simulated results of the relationship between power
      penalty and the different root-mean-square errors are concluded in order to put
      forward the requirement of machining precision of individual components. That
      will be helpful in optimizing the design of these groups in the optical receiver.

PMID- 24922021
TI  - Role of dynamic effects in the characterization of multilayers by means of power
      spectral density.
AB  - In this paper, we present measurements of angle- and wavelength-resolved diffuse
      scattering of EUV radiation on a Mo/Si multilayer. Our sample is optimized for
      high reflectivity at 13.5 nm wavelength near-normal incidence. We present a
      rigorous theoretical analysis of the off-specular EUV scattering on the basis of
      the distorted-wave Born approximation. We prove that the determination of the
      interface roughness power spectral density (PSD) is only possible by considering
      geometry-dependent and dynamic contributions. The scattering from multilayer
      mirrors leads to an intrinsic enhancement in off-specular intensity independent
      of roughness properties. The thickness oscillations in the scattering intensity
      (Kiessig fringes) are found to cause additional dynamic enhancement in analogy to
      Bragg-like peaks for grazing incidence geometry. Considering these effects, the
      interface PSD is consistently determined. 

PMID- 24922022
TI  - Easy-aligned off-axis three-mirror system with wide field of view using freeform
      surface based on integration of primary and tertiary mirror.
AB  - An off-axis three-mirror system (OTS) was designed based on the primary mirror
      and tertiary mirror (TM) integrated on a single substrate in order to solve the
      OTS drawbacks, such as the alignment difficulty and the large opto-mechanical
      weight. Furthermore, an optical freeform surface that can increase the optimizing
      degrees of freedom (DOF) was applied on the TM in order to achieve a wide field
      of view (FOV). An example with a focal length of 1200 mm, F-number of 12, and FOV
      of 10 degrees *4 degrees  was given, and the maximum wave front error (WFE) RMS
      was 0.0126lambda, indicating a good imaging quality. The design result shows that
      the number of alignment DOF was reduced from 12 to 6, and the weight of the
      mirror support assembly can also be lighter. An XY polynomial, established as an
      even function of x, was employed as the TM surface, so we obtained an axial
      symmetrical imaging quality about the x axis, and the axial symmetry aberration
      performance also brings considerable convenience to alignment and testing for the
      OTS. 

PMID- 24922023
TI  - Standoff two-color quantum ghost imaging through turbulence.
AB  - Recently, a two-color quantum ghost imaging configuration was proposed by
      Karmakar et al. [Phys. Rev. A81, 033845 (2010)]. By illuminating an object
      located far away from the source and detector, with a signal beam of long
      wavelength to avoid absorption of short wavelengths in the atmosphere while a
      reference beam of short wavelength is detected locally, this imaging
      configuration can be appropriate for standoff sensing. In practice, the signal
      beam must propagate through atmosphere in the presence of serious turbulence. We
      analyzed theoretically the performance of this ghost imaging configuration
      through turbulence. Based on the Gaussian state source model and extended Huygens
      Fresnel integral, a formula is derived to depict the ghost image formed through
      turbulence of a standoff reflective object. Numerical calculations are also given
      according to the formula. The results show that the image quality will be
      degraded by the turbulence, but the resolution can be improved by means of
      optimizing the wavelengths of the reference and signal beams even when the
      turbulence is very serious.

PMID- 24922024
TI  - Analytical description of interference between two misaligned and mismatched
      complete Gaussian beams.
AB  - A typical application for laser interferometers is a precision measurement of
      length changes that results in interferometric phase shifts. Such phase changes
      are typically predicted numerically, due to the complexity of the overlap
      integral that needs to be solved. In this paper we will derive analytical
      representations of the interferometric phase and contrast (aka fringe visibility)
      for two beam interferometers, both homodyne and heterodyne. The fundamental
      Gaussian beams can be arbitrarily misaligned and mismatched to each other. A
      limitation of the analytical result is that both beams must be detected
      completely, which can experimentally be realized by a sufficiently large single
      element photodetector. 

PMID- 24922025
TI  - Bistability and all-optical flip-flop with active microring resonator.
AB  - In this work, we study the bistability of an active nonlinear microring resonator
      and design a flip-flop based on the active microring resonator. In the presence
      of nonlinear and linear loss, we use Er-doped gain medium in the microring to
      obtain gain to compensate for the loss of the resonator. Both analytical and
      numerical methods are used to solve the propagation in the microring with double
      couplers, and we obtain the hysteresis loops of the microring. The results
      obtained by the two methods reveal that, in the presence of nonlinearity in
      microring resonators, the system exhibits bistability, and the gain in the
      microring leads to a decrease of the bias power when the active microring is
      taken as a bistable switcher. Basing on the bistability of the microring, we
      realize a set-reset flip-flop by adding a positive or negative feedback onto the
      bias. We also find that the duration of the set and reset pulses must exceed the
      field buildup time of the microring if we want to achieve the switching of the
      bias signal. In our design, the duration time is about 2 ps.

PMID- 24922026
TI  - Residual dispersion compensation over the S + C + L + U wavelength bands using
      highly birefringent octagonal photonic crystal fiber.
AB  - An octagonal photonic crystal fiber (PCF) with an elliptical shape in the center
      core is numerically investigated for residual dispersion compensation in the
      wavelength range 1460-1675 nm. The designed fiber exhibits flattened negative
      dispersion over the S + C + L + U wavelength bands and an average dispersion of 
      465.5 ps/(nm.km) with an absolute dispersion variation of 10.5 ps/(nm.km). In
      addition, the proposed PCF shows a high birefringence of 2.68*10(-2) at the
      operating wavelength 1550 nm, which meets the requirement of high birefringence.
      Moreover, the variation of two air holes in the first ring up to 5% ensures an
      average dispersion of -491.5 ps/(nm.km) with a dispersion variation of 13
      ps/(nm.km), and birefringence reaches up to 3*10(-2). Furthermore, to evaluate
      the sensitivity of the fiber dispersion properties, +/-5% variation in the
      optimum parameters is studied.

PMID- 24922027
TI  - Photoluminescence characterization of KH2PO4 crystal: application to three
      dimensional growth-sector identification.
AB  - In this work, rapidly grown KH2PO4 (KDP) crystals extracted from the prismatic
      and the pyramidal growth sectors of crystal boules were analyzed using
      photoluminescence measurements. From the spectra, we deduced a robust criterion
      to discriminate between both growth sectors in an unknown KDP plate. Moreover,
      spatially resolved photoluminescence was shown to enable a local probing of
      different planes in the bulk of the material leading to accurate and
      nondestructive three-dimensional mapping of the sector boundary, which is often
      the weakest point in terms of laser-damage resistance in rapidly grown KDP
      crystals.

PMID- 24922028
TI  - Determination of the surface form error of a spherical mirror with phase shifting
      Sagnac interferometer.
AB  - A polarization Sagnac interferometer (SI) is used to produce two laterally
      separated, identical, convergent emergent beams with linear orthogonal
      polarizations. The emergent p-polarized and s-polarized beams converge toward
      their respective focal points. The test and reference spherical mirrors are
      placed at confocal positions with respect to the s and p focal points so as to
      normally reflect back the test and reference beams through the SI that recombines
      the test and reference waves. Polarization phase shifting interferometry is
      applied to obtain the surface form error of the test surface with respect to the
      reference surface. A two-step measurement procedure eliminates the system
      aberrations. Results obtained for a concave spherical test surface with respect
      to a convex spherical reference surface are presented. The optical configuration
      is relatively less susceptible to external mechanical vibration. 

PMID- 24922029
TI  - Corrective finishing of extreme ultraviolet photomask blanks by precessed bonnet
      polisher.
AB  - The progressive transition from Excimer to extreme ultraviolet (EUV) lithography
      is driving a need for flatter and smoother photomask blanks. It is, however,
      proving difficult to meet the next-generation specification with the conventional
      chemical mechanical polishing technology commonly used for finishing photomask
      blanks. This paper reports on the application of subaperture computer numerical
      control precessed bonnet polishing technology to the corrective finishing of
      photomask substrates for EUV lithography. Full-factorial analysis was used to
      identify process parameters capable of delivering microroughness below 0.5 nm rms
      while retaining relatively high removal rates. Experimental results show that
      masks prepolished to 300-600 nm peak-to-valley (P-V) flatness by
      chemical/mechanical polishing can then be improved down to 50-100 nm P-V flatness
      using the automated technology described in this paper. A series of edge
      polishing experiments also hints at the possibility of increasing the quality
      area beyond the 142 mm square defined in the official EUV photomask
      specification. 

PMID- 24922030
TI  - High-repetition-rate and short-pulse-width electro-optical cavity-dumped
      YVO4/Nd:GdVO4 laser.
AB  - In this paper, an electro-optical cavity-dumped 1.06 MUm laser using
      YVO4/Nd:GdVO4 composite crystal under 808 nm diode-laser pumping was reported.
      Theoretical calculations showed that the temperature distribution in
      YVO4/Nd:GdVO4 crystal was lower than that in GdVO4/Nd:GdVO4 and Nd:GdVO4 crystals
      under the same conditions. A constant 3.8+/-0.3  ns pulse width was obtained and
      the repetition rate could reach up to 50 kHz with a maximum average output power
      of 5.6 W and slope efficiency of 40.7%, corresponding to a peak power of 31.1 kW.

PMID- 24922031
TI  - Derivative matrices of a skew ray for spherical boundary surfaces and their
      applications in system analysis and design.
AB  - In a previous paper [Appl. Opt.52, 4151 (2013)], we presented the first- and
      second-order derivatives of a ray for a flat boundary surface to design prisms.
      In this paper, that scheme is extended to determine the Jacobian and Hessian
      matrices of a skew ray as it is reflected/refracted at a spherical boundary
      surface. The validity of the proposed approach as an analysis and design tool is
      demonstrated using an axis-symmetrical system for illustration purpose. It is
      found that these two matrices can provide the search direction used by existing
      gradient-based schemes to minimize the merit function during the optimization
      stage of the optical system design process. It is also possible to make the
      optical system designs more automatic, if the image defects can be extracted from
      the Jacobian and Hessian matrices of a skew ray. 

PMID- 24922032
TI  - Three-dimensional inline inspection for substrate warpage and ball grid array
      coplanarity using stereo vision.
AB  - We present a method for full-field 3D measurement of substrate warpage and ball
      grid array coplanarity, which is suitable for inline back-end inspection and
      process monitoring. For evaluating the performance of the proposed system, the
      linearity between our system and a reference confocal microscope is studied by
      repeating measurements 35 times with a particular substrate sample (38  mm*28.5 
      mm). The point-to-point correlation coefficient with 1sigma between two methods
      is 0.968+/-0.002, and the 2sigma difference is 25.15+/-0.20  MUm for warpage
      measurement. 1sigma repeatability of the substrate warpage is 4.2 MUm. For BGA
      coplanarity inspection the bump level correlation coefficient is 0.957+/-0.001
      and the 2sigma difference is 28.79+/-0.14  MUm. 1sigma repeatability of BGA
      coplanarity is 3.7 MUm. Data acquisition takes about 0.2 s for full field
      measurements.

PMID- 24922033
TI  - Investigation of pitch and angle in the gradual-triangle lenticular lens for
      point-blank LED fog lamp.
AB  - The effects of different pitch and angle of gradual-triangle lenticular lens for
      the point-blank LED fog lamp were investigated under the standard of ECE R19. The
      novel LED fog lamp was assembled from a point-blank LED light source, a parabolic
      reflector, and a gradual-triangle lenticular lens. Light tracing analysis was
      used for the design of the gradual-triangle lenticular lens. The pitch, which
      varied from 1 to 6 mm, and the apex angle, which changed from 5 to 32 deg, were
      both investigated in regard to the gradual-triangle lenticular lens. The optimum
      pitch was 5 mm, and the efficiency of the lamp system and lenticular lens could
      reach 93% and 98.1% by simulation, respectively. The results of experiment had
      over 94%, which is similar to that of simulation by normalized cross correlation
      (NCC) for the light intensity.

PMID- 24922034
TI  - Improved algorithm based on a fiber loop: applications for optical water vapor
      sensor.
AB  - An improved algorithm based on a fiber loop optical structure is proposed for
      measurement of water vapor concentration. Compared with the traditional
      algorithm, the intrinsic loss of optical devices in the loop is no longer
      necessary to be accurately measured but instead is directly eliminated by
      normalization. The concentration of the analyte can be determined by only two
      pulses without the need for exponential curve fitting, which leads to a
      significant reduction in the amount of data required to make a measurement. The
      restriction on the inherent loss of the fiber loop system also can be eased. In
      addition, a background absorption problem caused by the water vapor existing
      inside internal end-face gaps of optical components is solved. The mean absolute
      error of 29 parts per million by volume has been achieved with a 6.5 cm gas gap
      by using the new algorithm. 

PMID- 24922035
TI  - Simultaneous measurement of phase and local orientation of linearly polarized
      light: implementation and measurement results.
AB  - Optical components manipulating both polarization and phase of wave fields find
      many applications in today's optical systems. With modern lithography methods it
      is possible to fabricate optical elements with nanostructured surfaces from
      different materials capable of generating spatially varying, locally linearly
      polarized-light distributions, tailored to the application in question. Since
      such elements in general also affect the phase of the light field, the
      characterization of the function of such elements consists in measuring the phase
      and the polarization of the generated light, preferably at the same time. Here,
      we will present first results of an interferometric approach for a simultaneous
      and spatially resolved measurement of both phase and polarization, as long as the
      local polarization at any point is linear (e.g., for radially or azimuthally
      polarized light). 

PMID- 24922036
TI  - Portable multispectral imaging system based on light-emitting diodes for spectral
      recovery from 370 to 1630 nm.
AB  - To expand and investigate the potential of spectral imaging, we developed a
      portable multispectral system using light-emitting diodes. This system recovers
      spectral information from the UV to the near IR over a large area using two
      different image sensors synchronized with 23 bands of illumination. The system
      was assessed for spectral reconstruction through simulations and experimental
      measurements by means of two methods of spectral reconstruction and three
      different evaluation metrics. The results over a Macbeth ColorChecker chart and
      other samples, including pigments usually employed in art paintings, are compared
      and discussed. The portable multispectral system using LEDs constitutes a cost
      effective and versatile method for spectral imaging. 

PMID- 24922037
TI  - Approach to visualization of and optical sensing by Bloch surface waves in noble
      or base metal-based plasmonic photonic crystal slabs.
AB  - The Bloch surface wave resonance (SWR) was visualized with the aid of plasmon
      absorption in a dielectric/metal/dielectric sandwich terminating a one
      dimensional photonic crystal (PhC). An SWR peak in calculated spectra of such a
      plasmonic photonic crystal (PPhC) slab comprising a noble or base metal layer was
      demonstrated to be sensitive to a negligible variation of refractive index of a
      medium adjoining to the slab. The considered structure of PPhC slabs can be of
      practical importance because the metal layer is protected by a capping dielectric
      layer from contact with analytes and, consequently, from deterioration. We found
      that, in case of PPhC slabs, gold (the key element of the surface plasmon
      resonance-based biosensors) can be replaced by other metals. The PPhC-based
      sensors can be low-cost, reusable, and robust sensors having a sensitivity
      surpassing that of the known optical sensors. 

PMID- 24922038
TI  - Observation of the waveguide resonance in a periodically patterned high
      refractive index broadband antireflection coating.
AB  - Grating waveguide structures have been prepared by the deposition of a high
      refractive index broadband antireflection coating onto a patterned fused silica
      substrate. Aluminum oxide and hafnium oxide as well as mixtures thereof have been
      used as coating materials. Optical reflection measurements combined with atomic
      force microscopy have been used to characterize the structures. Upon illumination
      with a TE wave, the best structure shows a narrow reflection peak located at 633
      nm at an incidence angle of about 17 degrees . The peak reflectance of that
      sample accounts for more than 89%. Off-resonance interference structures appear
      strongly suppressed in the spectrum between 450 and 800 nm because of the
      characteristics of the designed antireflection layer. The structure thus
      possesses a notch filter spectral characteristic in a broad spectral range. 

PMID- 24922039
TI  - Experimental verification of compressive reflectance field acquisition.
AB  - We demonstrate compressive sensing (CS) of the eight-dimensional reflectance
      field (RF), which describes spatial and angular information of light rays toward
      and from an object. The RF is also known as the bidirectional scattering surface
      reflectance distribution function. In this method, incident rays and reflected
      rays to/from the object are modulated by variable coding masks, and the modulated
      rays are multiplexed onto an image sensor. The images captured with multiple mask
      patterns are decoded by a CS algorithm. The RF of the object was successfully
      reconstructed from less than half of the number of measurements required with
      conventional methods. 

PMID- 24922040
TI  - Evaluation of the Military Functional Assessment Program: Preliminary Assessment
      of the Construct Validity Using an Archived Database of Clinical Data.
AB  - BACKGROUND: Several important factors must be considered when deciding to return
      a soldier to duty after a traumatic brain injury (TBI). Premature return
      increases risk for not only second-impact syndrome during the acute phase but
      also permanent changes from repetitive concussions. Thus, there is a critical
      need for return-to-duty (RTD) assessment criteria that encompass the spectrum of
      injury and disease experienced by US soldiers, particularly TBI. OBJECTIVES: To
      provide evidence-based standards to eventually serve as criteria for operational
      competence and performance of a soldier after injury. Specifically, the
      relationships between clinical assessments and novel military-specific tasks were
      evaluated. METHOD: Exploratory analyses (including nonparametric tests and
      Spearman rank correlations) of an archived database. PARTICIPANTS: A total of 79
      patients with TBI who participated in an RTD assessment program at a US Army
      rehabilitation and recovery center. MAIN MEASURES: Military Functional Assessment
      Program (to determine a soldier's operational competence and performance after
      TBI) tasks; Dizziness Handicap Inventory; Dynamic Visual Acuity (vestibular
      function); Sensory Organization Test (postural control); Repeatable Battery for
      the Assessment of Neuropsychological Status (neuropsychological screening test);
      Beck Depression Inventory-II; Beck Anxiety Inventory; Comprehensive Trail Making
      Test (visual search and sequencing); posttraumatic stress disorder checklist
      military version; Alcohol Use Disorders Identification Test; Epworth Sleepiness
      Scale; Patient Health Questionnaire; and Military Acute Concussion Evaluation.
      RESULTS: Selected military operational assessment tasks correlated significantly
      with clinical measures of vestibular function, psychological well-being, and
      cognitive function. Differences on occupational therapy assessments, a concussion
      screening tool, and a self-report health questionnaire were seen between those
      who passed and those who failed the RTD assessment. Specifically, those who
      passed the RTD assessment scored more favorably on these clinical assessments.
      CONCLUSIONS: This study demonstrated convergent validity between Military
      Functional Assessment Program tasks and clinical assessment scores. The Military
      Functional Assessment Program shows promise for augmenting decision making
      related to RTD and soldier skills. Additional research is needed to determine the
      effectiveness of this program in predicting RTD success.

PMID- 24922041
TI  - The Relationship Between Postconcussive Symptoms and Quality of Life in Veterans
      With Mild to Moderate Traumatic Brain Injury.
AB  - OBJECTIVE: To assess the relationship between postconcussive symptoms and quality
      of life (QOL) in Veterans with mild to moderate traumatic brain injury (TBI).
      METHODS: Sixty-one Operation Enduring Freedom/Operation Iraqi Freedom/Persian
      Gulf War Veterans with a history of mild or moderate TBI, more than 6 months
      postinjury, and 21 demographically matched Veteran controls were administered
      self-report measures of QOL (World Health Organization Quality of Life-BREF) and
      postconcussive symptom severity (Neurobehavioral Symptom Inventory). RESULTS:
      Perceived QOL was significantly worse in Veterans with mild-moderate TBI than in
      controls. In the TBI group, QOL was predominantly associated with affective
      symptoms, and moderate to strong correlations with fatigue and depression were
      evident across all QOL areas. Multivariate analyses revealed depression and
      fatigue to be the best predictors of Psychological, Social, and Environmental
      QOL, whereas sleep difficulty best predicted Physical QOL in mild-moderate TBI.
      CONCLUSION: Veterans with post-acute mild-moderate TBI evidence worse QOL than
      demographically matched Veteran controls. Affective symptoms, and specifically
      those of fatigue, depression, and sleep difficulty, appear to be the most
      relevant postconcussive symptoms predicting QOL in this population. These
      findings underscore the importance of examining specific symptoms as they relate
      to post-acute TBI QOL and provide guidance for treatment and intervention
      studies.

PMID- 24922042
TI  - The Reliability of a Computer-Assisted Telephone Interview Version of the Ohio
      State University Traumatic Brain Injury Identification Method.
AB  - OBJECTIVES: Provide test-retest reliability (>5 months) of the Ohio State
      University Traumatic Brain Injury Identification Method modified for use as a
      computer-assisted telephone interview (CATI) to capture traumatic brain injury
      (TBI) and other substantial bodily injuries among a representative sample of
      noninstitutionalized adults living in Colorado. DESIGN: Four subsamples of 50
      individuals, including people with no major lifetime injury, a major lifetime
      injury but no TBI, TBI with no loss of consciousness, and TBI with loss of
      consciousness, were interviewed using the CATI Ohio State University Traumatic
      Brain Injury Identification Method between 6 and 18 months after an initial
      interview. PARTICIPANTS: Stratified random sample of Coloradans (n = 200)
      selected from a larger study of TBI. PRIMARY MEASURES: Cumulative, Severity and
      Age-related indices were assessed for long-term reliability. Cumulative indices
      were those that summed the total number of specific TBI severities across the
      lifetime; Severity indices included measures of the most severe type of injury
      incurred throughout the lifetime; and Age-related indices assessed the timing of
      specific injury types across the lifespan. RESULTS: Test-retest reliabilities
      ranged from poor to excellent. The indices demonstrating the greatest reliability
      were Severity measures, with intraclass correlations for ordinal indices ranging
      from 0.62 to 0.78 and Cohen kappa ranging from 0.50 to 0.62. One Cumulative
      outcome demonstrated high reliability (0.70 for number of TBIs with loss of
      consciousness >=30 minutes), while the remaining Cumulative outcomes demonstrated
      low reliability, ranging from 0.06 to 0.21. Age-related test-retest reliabilities
      were fair to poor, with intraclass correlations of 0.38 to 0.49 and Cohen kappa
      of 0.32 and 0.34. CONCLUSION: The CATI-modified Ohio State University Traumatic
      Brain Injury Identification Method used in this study is an effective measure for
      evaluating the maximum TBI severity incurred throughout the lifetime within a
      general population survey. The CATI measure is not recommended for use in
      determining cumulative counts of lifetime incidence of TBI.

PMID- 24922044
TI  - Safety and efficacy of first-generation and second-generation drug-eluting stents
      in the setting of acute coronary syndromes.
AB  - Drug-eluting stents (DESs) are known to reduce in-stent restenosis rate, compared
      with bare metal stents (BMSs). Stent thrombosis, one of the most dangerous
      complications of DES, has emerged as a major concern. This issue has limited the
      use of DES in unstable coronary artery disease till recent years. In fact, acute
      coronary syndrome (ACS) and the subsequent activation of the hemocoagulative
      pathway could represent a prothrombotic environment, thus limiting the use of DES
      in this situation. Nowadays, there is increasing evidence in literature of
      similar stent thrombosis rates both for BMS and DES in ACS, and most
      interventional cardiologists are confident with the use of DES in ACS. The aim of
      this article is to review the current literature on this topic in order to
      compare first-generation and second-generation DES vs. BMS as concerns safety and
      efficacy. 

PMID- 24922045
TI  - Intracoronary optical coherence tomography: a review of clinical applications.
AB  - Optical coherence tomography (OCT) is a light-based technology that provides very
      high spatial resolution images. OCT has been initially employed as a research
      tool to investigate plaque morphology and stent strut coverage. The introduction
      of frequency domain OCT allowing fast image acquisition during a prolonged
      contrast injection via the guiding catheter has made OCT applicable for guidance
      of coronary interventions. In this manuscript, the various applications of OCT
      are reviewed, from assessment of plaque vulnerability and severity to
      characteristics of unstable lesions and thrombus burden to stent optimization and
      evaluation of late results. 

PMID- 24922043
TI  - Global Outcome Trajectories After TBI Among Survivors and Nonsurvivors: A
      National Institute on Disability and Rehabilitation Research Traumatic Brain
      Injury Model Systems Study.
AB  - OBJECTIVE: To compare long-term functional outcome trajectories of individuals
      with traumatic brain injury (TBI) who survive with those who expire more than 5
      years postinjury, using individual growth curve analysis. DESIGN: Secondary
      analysis of data from a multicenter longitudinal cohort study. SETTING: Acute
      inpatient rehabilitation facilities that are current or former TBI Model Systems.
      PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI.
      MAIN OUTCOME MEASURES: Glasgow Outcome Scale-Extended; Disability Rating Scale.
      RESULTS: Individuals in the TBI Model Systems who expire several years after
      injury demonstrate worse functional status at baseline and a steeper rate of
      decline over time as measured by both the Glasgow Outcome Scale-Extended and the
      Disability Rating Scale. There was significant variability in each growth
      parameter (P < .05) for both instruments. A reduced model was built for each
      outcome, including all covariates that related significantly to the growth
      parameters. An interactive tool was created for each outcome to generate
      individual-level trajectories based on various combinations of covariate values.
      CONCLUSION: Individuals with TBI who die several years after injury demonstrate
      functional trajectories that differ markedly from those of survivors.
      Opportunities should be sought for health management interventions to improve
      health and longevity after TBI.

PMID- 24922046
TI  - Design of the rosuvastatin pretreatment to reduce embolization during Carotid
      Artery Stenting trial.
AB  - BACKGROUND: Carotid artery stenting (CAS) is a worldwide diffuse intervention,
      but may be associated with distal plaque component embolization, and sometimes
      major and minor stroke. Statin use has been demonstrated to reduce
      atherosclerotic plaque burden, but its effect in reducing distal embolization
      during carotid stenting has not yet been well validated. AIMS: With the
      Rosuvastatin Pretreatment to Reduce Embolization during Carotid Artery Stenting
      trial, we aim to discover if a pretreatement with high doses of rosuvastatin in
      dyslipidemic patients is able to reduce periprocedural cerebral ischemic
      complications following carotid stenting. METHODS: This is a phase III
      prospective, randomized controlled trial. All consecutive patients with
      asymptomatic carotid stenosis at least 80% will be randomized to a 6-week
      rosuvastatin treatment followed by carotid stenting, and to direct carotid
      stenting. Carotid stenting will be performed following common practice with
      distal or proximal embolic protection. The primary efficacy end point of the
      trial will be the prevalence of 'relevant' embolization during CAS, as a
      surrogate end point for cerebral ischemic complications. Other laboratory and
      clinical data will be registered and patients will be followed up to 1 year. In
      order to obtain the expected superiority of statin pretreatment on primary end
      point, a population of 130 patients will be enrolled into the study. CONCLUSION:
      In conclusion, with the Rosuvastatin Pretreatment to Reduce Embolization during
      Carotid Artery Stenting trial, we want to evaluate whether a high dose of
      rosuvastatin for 6 weeks before CAS in asymptomatic patients with severe carotid
      stenosis is able to reduce the rate of plaque embolization during the procedure,
      thus suggesting a possible reduction in cerebral ischemic complications.

PMID- 24922047
TI  - Emergency department mental health presentations by people born in refugee source
      countries: an epidemiological logistic regression study in a Medicare Local
      region in Australia.
AB  - This study investigated if people born in refugee source countries are
      disproportionately represented among those receiving a diagnosis of mental
      illness within emergency departments (EDs). The setting was the Cities of Greater
      Dandenong and Casey, the resettlement region for one-twelfth of Australia's
      refugees. An epidemiological, secondary data analysis compared mental illness
      diagnoses received in EDs by refugee and non-refugee populations. Data was the
      Victorian Emergency Minimum Dataset in the 2008-09 financial year. Univariate and
      multivariate logistic regression created predictive models for mental illness
      using five variables: age, sex, refugee background, interpreter use and preferred
      language. Collinearity, model fit and model stability were examined. Multivariate
      analysis showed age and sex to be the only significant risk factors for mental
      illness diagnosis in EDs. 'Refugee status', 'interpreter use' and 'preferred
      language' were not associatedwith a mental health diagnosis following risk
      adjustment forthe effects ofage and sex. The disappearance ofthe univariate
      association after adjustment for age and sex is a salutary lesson for Medicare
      Locals and other health planners regarding the importance of adjusting analyses
      of health service data for demographic characteristics.

PMID- 24922048
TI  - Seven years of patient-controlled epidural analgesia in a Swedish hospital: a
      prospective survey.
AB  - BACKGROUND: Epidural analgesia for postoperative pain relief needs to be
      monitored regularly in order to evaluate benefits and avoid potential hazards.
      OBJECTIVES: To evaluate efficacy and safety profile of a ward-based regimen for
      postoperative epidural analgesia combining patient-controlled epidural analgesia
      (PCEA) and continuous epidural infusion (CEI). DESIGN: We conducted a prospective
      survey in all patients who received postoperative epidural analgesia between
      March 2004 and February 2011. PATIENTS: We analysed 4663 patients undergoing
      elective and acute surgery. SETTING: University hospital in Sweden. RESULTS: The
      median level of catheter insertion ranged from T8 in high abdominal surgery to
      T11 in gynaecological surgery. Mean infusion rate was 5.4 +/- 1.6 ml h and was
      adjusted for age. Mean duration was 3.3 +/- 2.1 days. Eighty-seven percent of the
      patients rated satisfaction 8 to 10 out of 10 on a post-treatment scale. Reasons
      for termination were elective in 77.1%, due to inadequate pain relief in 11.4%,
      due to suspected infection in 0.7% and due to other causes in 10.9%. Of the
      latter, dislodgement of the catheter (4.0%) and leakage from the puncture site
      (1.4%) dominated. Catheter reinsertion was performed in 5.3% of the patients, and
      in 5.0%, the treatment was converted into an intravenous (i.v.) morphine patient
      controlled analgesia regimen. The incidence of motor blockade was 1.7%, sedation
      2.1%, nausea 12.8% and pruritus 18.8%. Bolus doses accounted for 16% of the total
      infusion volume. No epidural haematoma was seen. One epidural abscess requiring
      antibiotic treatment occurred. CONCLUSION: Our prospective survey indicates that
      PCEA in combination with CEI is effective and relatively well tolerated. The
      incidence of side effects is generally low and severe adverse events very rare.

PMID- 24922049
TI  - Toxic and protective effects of inhaled anaesthetics on the developing animal
      brain: systematic review and update of recent experimental work.
AB  - BACKGROUND: Accumulating preclinical data indicate that neonatal exposure to
      general anaesthetics is detrimental to the central nervous system. Some studies,
      however, display potential protective effects of exactly the same anaesthetic
      agents on the immature brain. The effects of inhaled anaesthetics on the
      developing brain have received close attention from researchers, clinicians and
      the public in recent decades. OBJECTIVES: To summarise the preclinical evidence
      reported in the last 5 years on both the deleterious effects and the
      neuroprotective potential in special indications, of inhaled anaesthetics on the
      developing brain. DESIGN: A systematic review. DATA SOURCES: PubMed search
      performed in June 2013. ELIGIBILITY CRITERIA: Search terms included brain,
      development, inhaled anaesthetic, toxicity and protection within the scope of the
      last 5 years with animals. The reference lists of relevant articles and recent
      reviews were also hand-searched for additional studies. The type, dose and
      exposure duration of anaesthetics, species and age of animals, histopathologic
      indicators, outcomes and affected brain areas, neuro developmental test modules
      and outcomes, as well as other outcomes and comments were summarised. RESULTS:
      Two hundred and nineteen relevant titles were initially revealed. In total, 81
      articles were identified, with 68 articles assessing the detrimental effects
      induced by inhaled anaesthetics in the immature brain along with possible
      treatments. The remaining 13 articles focused on the protective profile of
      inhaled anaesthetics on perinatal hypoxic-ischaemic brain injury. Administration
      of inhaled anaesthetic agents to the immature brain was shown to be deleterious
      in several preclinical studies. In perinatal hypoxic-ischaemic brain injury
      models, pre- and postconditioning of inhalational anaesthetics exerted
      neuroprotective effects. CONCLUSION: The majority of studies have linked inhaled
      anaesthetics to toxic effects in the neonatal brain of rodents, piglets and
      primates. Only a few studies, however, could demonstrate long-lasting cognitive
      impairment. The results of inhalational anaesthetic-induced neuroprotection in
      perinatal hypoxic-ischaemic brain injury are a promising basis for more research
      in this field. In general, prospective clinical trials are needed to further
      differentiate the effects of inhaled anaesthetics on the immature brain.

PMID- 24922050
TI  - Comparative assessment of ELISAs using recombinant saposin-like protein 2 and
      recombinant cathepsin L-1 from Fasciola hepatica for the serodiagnosis of human
      Fasciolosis.
AB  - Two recombinant Fasciola hepatica antigens, saposin-like protein-2 (recSAP2) and
      cathepsin L-1 (recCL1), were assessed individually and in combination in enzyme
      linked immunosorbent assays (ELISA) for the specific serodiagnosis of human
      fasciolosis in areas of low endemicity as encountered in Central Europe. Antibody
      detection was conducted using ProteinA/ProteinG (PAG) conjugated to alkaline
      phosphatase. Test characteristics as well as agreement with results from an ELISA
      using excretory-secretory products (FhES) from adult stage liver flukes was
      assessed by receiver operator characteristic (ROC) analysis, specificity,
      sensitivity, Youdens J and overall accuracy. Cross-reactivity was assessed using
      three different groups of serum samples from healthy individuals (n=20), patients
      with other parasitic infections (n=87) and patients with malignancies (n=121).
      The best combined diagnostic results for recombinant antigens were obtained using
      the recSAP2-ELISA (87% sensitivity, 99% specificity and 97% overall accuracy)
      employing the threshold (cut-off) to discriminate between positive and negative
      reactions that maximized Youdens J. The findings showed that recSAP2-ELISA can be
      used for the routine serodiagnosis of chronic fasciolosis in clinical
      laboratories; the use of the PAG-conjugate offers the opportunity to employ, for
      example, rabbit hyperimmune serum for the standardization of positive controls.

PMID- 24922051
TI  - Negative example selection for protein function prediction: the NoGO database.
AB  - Negative examples - genes that are known not to carry out a given protein
      function - are rarely recorded in genome and proteome annotation databases, such
      as the Gene Ontology database. Negative examples are required, however, for
      several of the most powerful machine learning methods for integrative protein
      function prediction. Most protein function prediction efforts have relied on a
      variety of heuristics for the choice of negative examples. Determining the
      accuracy of methods for negative example prediction is itself a non-trivial task,
      given that the Open World Assumption as applied to gene annotations rules out
      many traditional validation metrics. We present a rigorous comparison of these
      heuristics, utilizing a temporal holdout, and a novel evaluation strategy for
      negative examples. We add to this comparison several algorithms adapted from
      Positive-Unlabeled learning scenarios in text-classification, which are the
      current state of the art methods for generating negative examples in low-density
      annotation contexts. Lastly, we present two novel algorithms of our own
      construction, one based on empirical conditional probability, and the other using
      topic modeling applied to genes and annotations. We demonstrate that our
      algorithms achieve significantly fewer incorrect negative example predictions
      than the current state of the art, using multiple benchmarks covering multiple
      organisms. Our methods may be applied to generate negative examples for any type
      of method that deals with protein function, and to this end we provide a database
      of negative examples in several well-studied organisms, for general use (The NoGO
      database, available at: bonneaulab.bio.nyu.edu/nogo.html). 

PMID- 24922053
TI  - S-oxygenation of thiocarbamides V: oxidation of tetramethylthiourea by chlorite
      in slightly acidic media.
AB  - The reaction between tetramethylthiourea (TTTU) and slightly acidic chlorite has
      been studied. The reaction is much faster than comparable oxidations of the
      parent thiourea compound as well as other substituted thioureas. The
      stoichiometry of the reaction in excess oxidant showed a complete desulfurization
      of the thiocarbamide to yield the corresponding urea and sulfate: 2ClO2(-) +
      (Me2N)2C ? S + H2O -> (Me2N)2C ? O + SO4(2-) + 2Cl(-) + 2H(+). The reaction
      mechanism is unique in that the most stable metabolite before formation of the
      corresponding urea is the S-oxide. This is one of the rare occasions in which a
      low-molecular-weight S-oxide has been stabilized without the aid of large steric
      groups. ESI-MS data show almost quantitative formation of the S-oxide and
      negligible formation of the sulfinic and sulfonic acids. TTTU, in contrast to
      other substituted thioureas, can only stabilize intermediate oxoacids, before
      formation of sulfate, in the form of zwitterions. With a stoichiometric excess of
      TTTU over oxidant, the TTTU dimer is the predominant product. Chlorine dioxide,
      which is formed from the reaction of excess chlorite and HOCl, is a very
      important reactant in the overall mechanism. It reacts rapidly with TTTU to
      reform ClO2(-). Oxidation of TTTU by chlorite has a complex dependence on acid as
      a result of chlorous acid dissociation and protonation of the thiol group on TTTU
      in high-acid conditions, which renders the thiol center a less effective
      nucleophile.

PMID- 24922055
TI  - Prevalence of trachoma in the north region of Cameroon: results of a survey in 15
      health districts.
AB  - BACKGROUND: To estimate the prevalence of trachoma in the North Region of
      Cameroon in order to facilitate the planning of trachoma control activities in
      this region, a survey was carried out in 2011 and 2012 in 15 health districts
      (HDs). METHODOLOGY: A cross-sectional, two-stage cluster random sampling survey
      was carried out. The survey focused on two target populations: children aged 1 to
      9 years for the prevalence of Trachomatous Inflammation-Follicular (TF) and those
      aged 15 and over for the prevalence of Trachomatous Trichiasis (TT). The sample
      frame was an exhaustive list of villages and neighborhoods of HDs. The World
      Health Organization simplified trachoma grading system was used for the
      recognition and registration of cases of trachoma. PRINCIPAL FINDINGS: 30,562
      children aged 1 to 9 years and 24,864 people aged 15 and above were examined. In
      children aged 1-9 years, the overall prevalence of TF was 4.2% (95% confidence
      intervals (CI): 4.0-4.5%). Three (3) of 15 HDs in the region showed TF prevalence
      of >= 10% (Poli, Rey Bouba, and Tchollire). The overall TT prevalence was 0.25%
      (95% CI: 0.20-0.33%). There were estimated 1265 TT cases in the region. The
      prevalence of blindness was 0.01% (95% CI: 0.00-0.03%), low vision was 0.11% (95%
      CI: 0.07-0.17%), and corneal opacity was 0.22% (95% CI: 0.17-0.29%).
      CONCLUSIONS/SIGNIFICANCE: This survey provides baseline data for the planning of
      activities to control trachoma in the region. The overall prevalence of TF in the
      region is 4.2%, and that of TT is 0.2%; three HDs have a TF prevalence >= 10%.
      These three HDs are eligible for mass drug administration with azythromycin,
      along with the implementation of the "F" and "E" components of the SAFE strategy.

PMID- 24922054
TI  - JNK controls the onset of mitosis in planarian stem cells and triggers apoptotic
      cell death required for regeneration and remodeling.
AB  - Regeneration of lost tissues depends on the precise interpretation of molecular
      signals that control and coordinate the onset of proliferation, cellular
      differentiation and cell death. However, the nature of those molecular signals
      and the mechanisms that integrate the cellular responses remain largely unknown.
      The planarian flatworm is a unique model in which regeneration and tissue renewal
      can be comprehensively studied in vivo. The presence of a population of adult
      pluripotent stem cells combined with the ability to decode signaling after
      wounding enable planarians to regenerate a complete, correctly proportioned
      animal within a few days after any kind of amputation, and to adapt their size to
      nutritional changes without compromising functionality. Here, we demonstrate that
      the stress-activated c-jun-NH2-kinase (JNK) links wound-induced apoptosis to the
      stem cell response during planarian regeneration. We show that JNK modulates the
      expression of wound-related genes, triggers apoptosis and attenuates the onset of
      mitosis in stem cells specifically after tissue loss. Furthermore, in pre
      existing body regions, JNK activity is required to establish a positive balance
      between cell death and stem cell proliferation to enable tissue renewal,
      remodeling and the maintenance of proportionality. During homeostatic degrowth,
      JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling.
      Our findings indicate that JNK-dependent apoptotic cell death is crucial to
      coordinate tissue renewal and remodeling required to regenerate and to maintain a
      correctly proportioned animal. Hence, JNK might act as a hub, translating wound
      signals into apoptotic cell death, controlled stem cell proliferation and
      differentiation, all of which are required to coordinate regeneration and tissue
      renewal. 

PMID- 24922056
TI  - Percutaneous fetal cardiac interventions for structural heart disease.
AB  - INTRODUCTION: Prenatal diagnosis provides valuable information regarding a
      variety of congenital heart defects. Some defects occur early in gestation with
      little change throughout pregnancy, whereas others evolve during mid and late
      gestation. Fetal cardiac intervention (FCI) affords the opportunity to interrupt
      progression of disease in this latter category, resulting in improved perinatal
      and lifelong outcomes. AIM: This chapter addresses three lesions for which
      percutaneous FCI can be utilized: (1) aortic stenosis with evolving hypoplastic
      left heart syndrome, for which aortic valvuloplasty may prevent left ventricular
      hypoplasia and has yielded a biventricular circulation in approximately one third
      of cases; (2) hypoplastic left heart syndrome with intact atrial septum, for
      which relief of atrial restriction has potential to improve perinatal survival;
      and (3) pulmonary atresia with intact ventricular septum and evolving right
      ventricular hypoplasia, for which pulmonary valvuloplasty has resulted in a
      biventricular circulation in the majority of patients. The pathophysiology,
      rationale for intervention, patient selection criteria, procedural technique, and
      outcomes for each lesion will be reviewed. This chapter will also review
      complications of FCI and their treatment, and maternal and fetal anesthesia
      specific to FCI. The importance of a specialized center with experience managing
      infants delivered after FCI will also be addressed.

PMID- 24922057
TI  - BioAssemblyModeler (BAM): user-friendly homology modeling of protein homo- and
      heterooligomers.
AB  - Many if not most proteins function in oligomeric assemblies of one or more
      protein sequences. The Protein Data Bank provides coordinates for biological
      assemblies for each entry, at least 60% of which are dimers or larger assemblies.
      BioAssemblyModeler (BAM) is a graphical user interface to the basic steps in
      homology modeling of protein homooligomers and heterooligomers from the
      biological assemblies provided in the PDB. BAM takes as input up to six different
      protein sequences and begins by assigning Pfam domains to the target sequences.
      The program utilizes a complete assignment of Pfam domains to sequences in the
      PDB, PDBfam (http://dunbrack2.fccc.edu/protcid/pdbfam), to obtain templates that
      contain any or all of the domains assigned to the target sequence(s). The
      contents of the biological assemblies of potential templates are provided, and
      alignments of the target sequences to the templates are produced with a profile
      profile alignment algorithm. BAM provides for visual examination and mouse
      editing of the alignments supported by target and template secondary structure
      information and a 3D viewer of the template biological assembly. Side-chain
      coordinates for a model of the biological assembly are built with the program
      SCWRL4. A built-in protocol navigation system guides the user through all stages
      of homology modeling from input sequences to a three-dimensional model of the
      target complex. AVAILABILITY: http://dunbrack.fccc.edu/BAM.

PMID- 24922059
TI  - A reweighted l1-minimization based compressed sensing for the spectral estimation
      of heart rate variability using the unevenly sampled data.
AB  - In this paper, a reweighted l1-minimization based Compressed Sensing (CS)
      algorithm incorporating the Integral Pulse Frequency Modulation (IPFM) model for
      spectral estimation of HRV is introduced. Knowing as a novel sensing/sampling
      paradigm, the theory of CS asserts certain signals that are considered sparse or
      compressible can be possibly reconstructed from substantially fewer measurements
      than those required by traditional methods. Our study aims to employ a novel
      reweighted l1-minimization CS method for deriving the spectrum of the modulating
      signal of IPFM model from incomplete RR measurements for HRV assessments. To
      evaluate the performance of HRV spectral estimation, a quantitative measure,
      referred to as the Percent Error Power (PEP) that measures the percentage of
      difference between the true spectrum and the spectrum derived from the incomplete
      RR dataset, was used. We studied the performance of spectral reconstruction from
      incomplete simulated and real HRV signals by experimentally truncating a number
      of RR data accordingly in the top portion, in the bottom portion, and in a random
      order from the original RR column vector. As a result, for up to 20% data
      truncation/loss the proposed reweighted l1-minimization CS method produced, on
      average, 2.34%, 2.27%, and 4.55% PEP in the top, bottom, and random data
      truncation cases, respectively, on Autoregressive (AR) model derived simulated
      HRV signals. Similarly, for up to 20% data loss the proposed method produced
      5.15%, 4.33%, and 0.39% PEP in the top, bottom, and random data-truncation cases,
      respectively, on a real HRV database drawn from PhysioNet. Moreover, results
      generated by a number of intensive numerical experiments all indicated that the
      reweighted l1-minimization CS method always achieved the most accurate and high
      fidelity HRV spectral estimates in every aspect, compared with the l1
      minimization based method and Lomb's method used for estimating the spectrum of
      HRV from unevenly sampled RR data. 

PMID- 24922058
TI  - Comparison of REST cistromes across human cell types reveals common and context
      specific functions.
AB  - Recent studies have shown that the transcriptional functions of REST are much
      broader than repressing neuronal genes in non-neuronal systems. Whether REST
      occupies similar chromatin regions in different cell types and how it interacts
      with other transcriptional regulators to execute its functions in a context
      dependent manner has not been adequately investigated. We have applied ChIP-seq
      analysis to identify the REST cistrome in human CD4+ T cells and compared it with
      published data from 15 other cell types. We found that REST cistromes were
      distinct among cell types, with REST binding to several tumor suppressors
      specifically in cancer cells, whereas 7% of the REST peaks in non-neuronal cells
      were ubiquitously called and <25% were identified for >= 5 cell types.
      Nevertheless, using a quantitative metric directly comparing raw ChIP-seq
      signals, we found the majority (~80%) was shared by >= 2 cell types. Integration
      with RNA-seq data showed that REST binding was generally correlated with low gene
      expression. Close examination revealed that multiple contexts were correlated
      with reduced expression of REST targets, e.g., the presence of a cognate RE1
      motif and cellular specificity of REST binding. These contexts were shown to play
      a role in differential corepressor recruitment. Furthermore, transcriptional
      outcome was highly influenced by REST cofactors, e.g., SIN3 and EZH2 co-occupancy
      marked higher and lower expression of REST targets, respectively. Unexpectedly,
      the REST cistrome in differentiated neurons exhibited unique features not
      observed in non-neuronal cells, e.g., the lack of RE1 motifs and an association
      with active gene expression. Finally, our analysis demonstrated how REST could
      differentially regulate a transcription network constituted of miRNAs, REST
      complex and neuronal factors. Overall, our findings of contexts playing critical
      roles in REST occupancy and regulatory outcome provide insights into the
      molecular interactions underlying REST's diverse functions, and point to novel
      roles of REST in differentiated neurons.

PMID- 24922060
TI  - Pharmacokinetic compatibility of ginsenosides and Schisandra Lignans in Shengmai
      san: from the perspective of p-glycoprotein.
AB  - BACKGROUND: Phytochemical-mediated alterations in P-glycoprotein (P-gp) activity
      may result in herb-drug interactions by altering drug pharmacokinetics. Shengmai
      san, a traditional Chinese herbal medicine composed by Panax Ginseng, Ophiopogon
      Japonicus, and Schisandra Chinensis, is routinely being used for treating various
      coronary heart diseases. In our previous studies, Schisandra Lignans Extract
      (SLE) was proved as a strong P-gp inhibitor, and herein, the compatibility of
      Shengmai-san was studied by investigating the influence of SLE on the
      pharmacokinetics of the ginsenosides from the perspective of P-gp. METHODOLOGY:
      Pharmacokinetic experiments were firstly performed based on in vitro uptake,
      efflux and transport experiments in Caco-2, LLC-PK1 wild-type and MDR1
      overexpressing L-MDR1 cells. During the whole experiment, digoxin, a classical P
      gp substrate, was used as a positive control drug to verify the cells used are
      the valid models. Meanwhile, the effects of SLE on the pharmacokinetics of
      ginsenosides were further investigated in rats after single-dose and multi-dose
      of SLE. RESULTS AND CONCLUSIONS: The efflux ratios of ginsenoside Rb2, Rc, Rg2,
      Rg3, Rd and Rb1 were found more than 3.5 in L-MDR1 cells and can be decreased
      significantly by verapamil (a classical P-gp inhibitor). Contrarily, the efflux
      ratios of other ginsenosides (Rh1, F1, Re, and Rg1) were lower than 2.0 and not
      affected by verapamil. Then, the effects of SLE on the uptake and transport of
      ginsenosides were investigated, and SLE was found can significantly enhance the
      uptake and inhibit the efflux ratio of ginsenoside Rb2, Rc, Rg2, Rg3, Rd and Rb1
      in Caco-2 and L-MDR1 cells. Besides, In vivo experiments showed that single-dose
      and multi-dose of SLE at 500 mg/kg could increase the area under the plasma
      concentration time curve of Rb2, Rc and Rd significantly without affecting
      terminal elimination half-time. In conclusion, SLE could enhance the exposure of
      ginsenosides Rb2, Rc, Rg2, Rg3, Rd and Rb1 significantly.

PMID- 24922061
TI  - Influence of Charged Groups on the Properties of Zwitterionic Moieties: A
      Molecular Simulation Study.
AB  - Zwitterionic carboxybetaine and sulfobetaine materials have shown an excellent
      ability to resist nonspecific protein adsorption. It is desirable to obtain a
      better understanding of zwitterionic materials based on their molecular
      structures. This work aims to understand the roles of charged groups in
      zwitterionic moieties and to design new protein-resistant zwitterionic moieties
      beyond carboxybetaine and sulfobetaine. We conducted molecular simulations to
      study the hydration, self-association, and protein interactions of 12
      zwitterionic moieties derived from three anionic groups (carboxylic, sulfonate,
      and sulfate) and four cationic groups (quaternary ammonium, tertiary ammonium,
      secondary ammonium, and primary ammonium). The partial charges of atoms in these
      moieties were obtained from quantum chemical calculations. Hydration was studied
      by evaluating the hydration free energy of moieties and the hydration structure
      and dynamics of the charged groups. All zwitterionic moieties have strong
      hydration, but their structural and dynamic properties depend on the types of
      cationic and anionic groups involved. The self-association and protein
      interactions of zwitterionic moieties also show relationships with the charged
      groups. Our simulation results indicate good protein-resistant ability of several
      zwitterionic moieties, one of which has also been shown by recent experiments.

PMID- 24922062
TI  - Retinoic acid therapy resistance progresses from unilineage to bilineage in HL-60
      leukemic blasts.
AB  - Emergent resistance can be progressive and driven by global signaling
      aberrations. All-trans retinoic acid (RA) is the standard therapeutic agent for
      acute promyelocytic leukemia, but 10-20% of patients are not responsive, and
      initially responsive patients relapse and develop retinoic acid resistance. The
      patient-derived, lineage-bipotent acute myeloblastic leukemia (FAB M2) HL-60 cell
      line is a potent tool for characterizing differentiation-induction therapy
      responsiveness and resistance in t(15;17)-negative cells. Wild-type (WT) HL-60
      cells undergo RA-induced granulocytic differentiation, or monocytic
      differentiation in response to 1,25-dihydroxyvitamin D3 (D3). Two sequentially
      emergent RA-resistant HL-60 cell lines, R38+ and R38-, distinguishable by RA
      inducible CD38 expression, do not arrest in G1/G0 and fail to upregulate CD11b
      and the myeloid-associated signaling factors Vav1, c-Cbl, Lyn, Fgr, and c-Raf
      after RA treatment. Here, we show that the R38+ and R38- HL-60 cell lines display
      a progressive reduced response to D3-induced differentiation therapy. Exploiting
      the biphasic dynamic of induced HL-60 differentiation, we examined if resistance
      related defects occurred during the first 24 h (the early or "precommitment"
      phase) or subsequently (the late or "lineage-commitment" phase). HL-60 were
      treated with RA or D3 for 24 h, washed and retreated with either the same,
      different, or no differentiation agent. Using flow cytometry, D3 was able to
      induce CD38, CD11b and CD14 expression, and G1/G0 arrest when present during the
      lineage-commitment stage in R38+ cells, and to a lesser degree in R38- cells.
      Clustering analysis of cytometry and quantified Western blot data indicated that
      WT, R38+ and R38- HL-60 cells exhibited decreasing correlation between phenotypic
      markers and signaling factor expression. Thus differentiation induction therapy
      resistance can develop in stages, with initial partial RA resistance and moderate
      vitamin D3 responsiveness (unilineage maturation block), followed by bilineage
      maturation block and progressive signaling defects, notably the reduced
      expression of Vav1, Fgr, and c-Raf. 

PMID- 24922064
TI  - Radiation-induced accelerated senescence: a fate worse than death?

PMID- 24922063
TI  - Leptin is an anti-apoptotic effector in placental cells involving p53
      downregulation.
AB  - Leptin, a peripheral signal synthetized by the adipocyte to regulate energy
      metabolism, can also be produced by placenta, where it may work as an autocrine
      hormone. We have previously demonstrated that leptin promotes proliferation and
      survival of trophoblastic cells. In the present work, we aimed to study the
      molecular mechanisms that mediate the survival effect of leptin in placenta. We
      used the human placenta choriocarcinoma BeWo and first trimester Swan-71 cell
      lines, as well as human placental explants. We tested the late phase of
      apoptosis, triggered by serum deprivation, by studying the activation of Caspase
      3 and DNA fragmentation. Recombinant human leptin added to BeWo cell line and
      human placental explants, showed a decrease on Caspase-3 activation. These
      effects were dose dependent. Maximal effect was achieved at 250 ng leptin/ml.
      Moreover, inhibition of endogenous leptin expression with 2 uM of an antisense
      oligonucleotide, reversed Caspase-3 diminution. We also found that the cleavage
      of Poly [ADP-ribose] polymerase-1 (PARP-1) was diminished in the presence of
      leptin. We analyzed the presence of low DNA fragments, products from apoptotic
      DNA cleavage. Placental explants cultivated in the absence of serum in the
      culture media increased the apoptotic cleavage of DNA and this effect was
      prevented by the addition of 100 ng leptin/ml. Taken together these results
      reinforce the survival effect exerted by leptin on placental cells. To improve
      the understanding of leptin mechanism in regulating the process of apoptosis we
      determined the expression of different intermediaries in the apoptosis cascade.
      We found that under serum deprivation conditions, leptin increased the anti
      apoptotic BCL-2 protein expression, while downregulated the pro-apoptotic BAX and
      BID proteins expression in Swan-71 cells and placental explants. In both models
      leptin augmented BCL-2/BAX ratio. Moreover we have demonstrated that p53, one of
      the key cell cycle-signaling proteins, is downregulated in the presence of leptin
      under serum deprivation. On the other hand, we determined that leptin reduced the
      phosphorylation of Ser-46 p53 that plays a pivotal role for apoptotic signaling
      by p53. Our data suggest that the observed anti-apoptotic effect of leptin in
      placenta is in part mediated by the p53 pathway. In conclusion, we provide
      evidence that demonstrates that leptin is a trophic factor for trophoblastic
      cells. 

PMID- 24922066
TI  - Mixed layer depth trends in the Bay of Biscay over the period 1975-2010.
AB  - Wintertime trends in mixed layer depth (MLD) were calculated in the Bay of Biscay
      over the period 1975-2010 using the Simple Ocean Data Assimilation (SODA)
      package. The reliability of the SODA database was confirmed correlating its
      results with those obtained from the experimental Argo database over the period
      2003-2010. An iso-thermal layer depth (TLD) and an iso-pycnal layer depth (PLD)
      were defined using the threshold difference method with DeltaT = 0.5 degrees C
      and Deltasigmatheta = 0.125 kg/m3. Wintertime trends of the MLD were calculated
      using winter extended (December-March) anomalies and annual maxima. Trends
      calculated for the whole Bay of Biscay using both parameters (TLD and PLD) showed
      to be dependent on the area. Thus, MLD became deeper in the southeastern corner
      and shallower in the rest of the area. Air temperature was shown to play a key
      role in regulating the different spatial behavior of the MLD. Negative air
      temperature trends localized in the southeastern corner coincide with MLD
      deepening in this area, while, positive air temperature trends are associated to
      MLD shoaling in the rest of the bay. Additionally, the temperature trend
      calculated along the first 700 m of the water column is in good agreement with
      the different spatial behavior revealed for the MLD trend. 

PMID- 24922065
TI  - RNase J is required for processing of a small number of RNAs in Rhodobacter
      sphaeroides.
AB  - All bacteria contain multiple exoribonucleases to ensure a fast breakdown of
      different RNA molecules, either for maturation or for complete degradation to the
      level of mononucleotides. This efficient RNA degradation plays pivotal roles in
      the post-transcriptional gene regulation, in RNA processing and maturation as
      well as in RNA quality control mechanisms and global adaption to stress
      conditions. Besides different 3'-to-5' exoribonucleases mostly with overlapping
      functions in vivo many bacteria additionally possess the 5'-to-3'
      exoribonuclease, RNase J, to date the only known bacterial ribonuclease with this
      activity. An RNA-seq approach was applied to identify specific targets of RNase J
      in the alpha-proteobacterium Rhodobacter sphaeroides. Only few transcripts were
      strongly affected by the lack of RNase J implying that its function is mostly
      required for specific processing/degradation steps in this bacterium. The
      accumulation of diverse RNA fragments in the RNase J deletion mutant points to
      RNA features that apparently cannot be targeted by the conventional 3'
      exoribonucleases in Gram-negative bacteria. 

PMID- 24922067
TI  - Long-term experiment on physiological responses to synergetic effects of ocean
      acidification and photoperiod in the Antarctic sea ice algae Chlamydomonas sp.
      ICE-L.
AB  - Studies on ocean acidification have mostly been based on short-term experiments
      of low latitude with few investigations of the long-term influence on sea ice
      communities. Here, the combined effects of ocean acidification and photoperiod on
      the physiological response of the Antarctic sea ice microalgae Chlamydomonas sp.
      ICE-L were examined. There was a general increase in growth, PSII photosynthetic
      parameters, and N and P uptake in continuous light, compared to those exposed to
      regular dark and light cycles. Elevated pCO2 showed no consistent effect on
      growth rate (p=0.8) and N uptake (p=0.38) during exponential phrase, depending on
      the photoperiod but had a positive effect on PSII photosynthetic capacity and P
      uptake. Continuous dark reduced growth, photosynthesis, and nutrient uptake.
      Moreover, intracellular lipid, mainly in the form of PUFA, was consumed at 80%
      and 63% in low and high pCO2 in darkness. However, long-term culture under high
      pCO2 gave a more significant inhibition of growth and Fv/Fm to high light stress.
      In summary, ocean acidification may have significant effects on Chlamydomonas sp.
      ICE-L survival in polar winter. The current study contributes to an understanding
      of how a sea ice algae-based community may respond to global climate change at
      high latitudes.

PMID- 24922068
TI  - Fragmentation of bicyclic gamma-silyloxy-beta-hydroxy-alpha-diazolactones as an
      approach to ynolides.
AB  - Medium-sized ynolides were prepared by the Lewis acid-mediated fragmentation of
      bicyclic gamma-silyloxy-beta-hydroxy-alpha-diazolactones in which the Cbeta
      Cgamma bond is the ring fusion bond. Although these lactone fragmentation
      substrates reacted somewhat less efficiently than their carbocyclic counterparts,
      the fragmentation provided 11-membered ynolides in up to 84% yield. Unlike prior
      fragmentations of similar substrates, elevated temperatures were required to
      obtain optimum yields of the ynolide products. The ynolides reported herein have
      ring sizes of 10 or 11, which are the smallest reported to date. 

PMID- 24922069
TI  - Platelet activation and anti-phospholipid antibodies collaborate in the
      activation of the complement system on platelets in systemic lupus erythematosus.
AB  - Anti-phospholipid (aPL) antibodies are important contributors to development of
      thrombosis in patients with the autoimmune rheumatic disease systemic lupus
      erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis
      is not fully understood but existing data suggest that platelets and the
      complement system are key components. Complement activation on platelets is seen
      in SLE patients, especially in patients with aPL antibodies, and has been related
      to venous thrombosis and stroke. The aim of this study was to investigate if aPL
      antibodies could support classical pathway activation on platelets in vitro as
      well as in SLE patients. Furthermore, we investigated if complement deposition on
      platelets was associated with vascular events, either arterial or venous, when
      the data had been adjusted for traditional cardiovascular risk factors. Finally,
      we analyzed if platelet complement deposition, both C1q and C4d, was specific for
      SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro
      as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement
      deposition on platelets was increased in SLE patients when compared with healthy
      individuals (p<0.0001). However, high levels of C4d deposition and a pronounced
      C1q deposition were also seen in patients with rheumatoid arthritis and systemic
      sclerosis. In SLE, C4d deposition on platelets was associated with platelet
      activation, complement consumption, disease activity and venous (OR = 5.3, p =
      0.02), but not arterial, thrombosis, observations which were independent of
      traditional cardiovascular risk factors. In conclusion, several mechanisms
      operate in SLE to amplify platelet complement deposition, of which aPL antibodies
      and platelet activation were identified as important contributors in this
      investigation. Complement deposition on platelets was identified as a marker of
      venous, but not arterial thrombosis, in SLE patients independently of traditional
      risk factors and aPL antibodies. Further studies are needed to elucidate the role
      of complement deposition on platelets in development of venous thrombosis. 

PMID- 24922070
TI  - Wnt3a mitigates acute lung injury by reducing P2X7 receptor-mediated alveolar
      epithelial type I cell death.
AB  - Acute lung injury (ALI) is characterized by pulmonary endothelial and epithelial
      cell damage, and loss of the alveolar-capillary barrier. We have previously shown
      that P2X7 receptor (P2X7R), a cell death receptor, is specifically expressed in
      alveolar epithelial type I cells (AEC I). In this study, we hypothesized that
      P2X7R-mediated purinergic signaling and its interaction with Wnt/beta-catenin
      signaling contributes to AEC I death. We examined the effect of P2X7R agonist 2'
      3'-O-(4-benzoylbenzoyl)-ATP (BzATP) and Wnt agonist Wnt3a on AEC I death in vitro
      and in vivo. We also assessed the therapeutic potential of Wnt3a in a clinically
      relevant ALI model of intratracheal lipopolysaccharide (LPS) exposure in
      ventilated mice. We found that the activation of P2X7R by BzATP caused the death
      of AEC I by suppressing Wnt/beta-catenin signaling through stimulating glycogen
      synthase kinase-3beta (GSK-3beta) and proteasome. On the other hand, the
      activation of Wnt/beta-catenin signaling by Wnt3a, GSK-3beta inhibitor, or
      proteasome inhibitor blocked the P2X7R-mediated cell death. More importantly,
      Wnt3a attenuated the AEC I damage caused by intratracheal instillation of BzATP
      in rats or LPS in ventilated mice. Our results suggest that Wnt3a overrides the
      effect of P2X7R on the Wnt/beta-catenin signaling to prevent the AEC I death and
      restrict the severity of ALI. 

PMID- 24922071
TI  - LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to
      breast cancer tumorigenesis and metastasis.
AB  - LncRNAs have critical roles in various biological processes ranging from
      embryonic development to human diseases, including cancer progression, although
      their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has
      been shown to contribute to the maintenance of induced pluripotent stem cells and
      embryonic stem cells. In this study, we discovered that linc-ROR was upregulated
      in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized
      human mammary epithelial cells induced an epithelial-to-mesenchymal transition
      (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell
      migration and invasion, which was accompanied by generation of stem cell
      properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and
      lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was
      associated with miRNPs and functioned as a competing endogenous RNA to mi-205.
      Specifically, linc-ROR prevented the degradation of mir-205 target genes,
      including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions
      as an important regulator of EMT and can promote breast cancer progression and
      metastasis through regulation of miRNAs. Potentially, the findings of this study
      implicate the relevance of linc-ROR as a possible therapeutic target for
      aggressive and metastatic breast cancers. 

PMID- 24922072
TI  - Genetic deficiency of neuronal RAGE protects against AGE-induced synaptic injury.
AB  - Synaptic dysfunction and degeneration is an early pathological feature of aging
      and age-related diseases, including Alzheimer's disease (AD). Aging is associated
      with increased generation and deposition of advanced glycation endproducts
      (AGEs), resulting from nonenzymatic glycation (or oxidation) proteins and lipids.
      AGE formation is accelerated in diabetes and AD-affected brain, contributing to
      cellular perturbation. The extent of AGEs' involvement, if at all, in alterations
      in synaptic structure and function is currently unknown. Here we analyze the
      contribution of neuronal receptor of AGEs (RAGE) signaling to AGE-mediated
      synaptic injury using novel transgenic neuronal RAGE knockout mice specifically
      targeted to the forebrain and transgenic mice expressing neuronal dominant
      negative RAGE (DN-RAGE). Addition of AGEs to brain slices impaired hippocampal
      long-term potentiation (LTP). Similarly, treatment of hippocampal neurons with
      AGEs significantly decreases synaptic density. Such detrimental effects are
      largely reversed by genetic RAGE depletion. Notably, brain slices from mice with
      neuronal RAGE deficiency or DN-RAGE are resistant to AGE-induced LTP deficit.
      Further, RAGE deficiency or DN-RAGE blocks AGE-induced activation of p38
      signaling. Taken together, these data show that neuronal RAGE functions as a
      signal transducer for AGE-induced synaptic dysfunction, thereby providing new
      insights into a mechanism by which the AGEs-RAGE-dependent signaling cascade
      contributes to synaptic injury via the p38 MAP kinase signal transduction
      pathway. Thus, RAGE blockade may be a target for development of interventions
      aimed at preventing the progression of cognitive decline in aging and age-related
      neurodegenerative diseases. 

PMID- 24922073
TI  - DYRK1A promotes dopaminergic neuron survival in the developing brain and in a
      mouse model of Parkinson's disease.
AB  - In the brain, programmed cell death (PCD) serves to adjust the numbers of the
      different types of neurons during development, and its pathological reactivation
      in the adult leads to neurodegeneration. Dual-specificity tyrosine-(Y)
      phosphorylation regulated kinase 1A (DYRK1A) is a pleiotropic kinase involved in
      neural proliferation and cell death, and its role during brain growth is
      evolutionarily conserved. Human DYRK1A lies in the Down syndrome critical region
      on chromosome 21, and heterozygous mutations in the gene cause microcephaly and
      neurological dysfunction. The mouse model for DYRK1A haploinsufficiency (the
      Dyrk1a(+/-) mouse) presents neuronal deficits in specific regions of the adult
      brain, including the substantia nigra (SN), although the mechanisms underlying
      these pathogenic effects remain unclear. Here we study the effect of DYRK1A copy
      number variation on dopaminergic cell homeostasis. We show that mesencephalic DA
      (mDA) neurons are generated in the embryo at normal rates in the Dyrk1a
      haploinsufficient model and in a model (the mBACtgDyrk1a mouse) that carries
      three copies of Dyrk1a. We also show that the number of mDA cells diminishes in
      postnatal Dyrk1a(+/-) mice and increases in mBACtgDyrk1a mice due to an abnormal
      activity of the mitochondrial caspase9 (Casp9)-dependent apoptotic pathway during
      the main wave of PCD that affects these neurons. In addition, we show that the
      cell death induced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), a
      toxin that activates Casp9-dependent apoptosis in mDA neurons, is attenuated in
      adult mBACtgDyrk1a mice, leading to an increased survival of SN DA neurons 21
      days after MPTP intoxication. Finally, we present data indicating that Dyrk1a
      phosphorylation of Casp9 at the Thr125 residue is the mechanism by which this
      kinase hinders both physiological and pathological PCD in mDA neurons. These data
      provide new insight into the mechanisms that control cell death in brain DA
      neurons and they show that deregulation of developmental apoptosis may contribute
      to the phenotype of patients with imbalanced DYRK1A gene dosage. 

PMID- 24922074
TI  - Loss of function of the ALS protein SigR1 leads to ER pathology associated with
      defective autophagy and lipid raft disturbances.
AB  - Intracellular accumulations of altered, misfolded proteins in neuronal and other
      cells are pathological hallmarks shared by many neurodegenerative diseases
      including amyotrophic lateral sclerosis (ALS). Mutations in several genes give
      rise to familial forms of ALS. Mutations in Sigma receptor 1 have been found to
      cause a juvenile form of ALS and frontotemporal lobar degeneration (FTLD). We
      recently described altered localization, abnormal modification and loss of
      function of SigR1 in sporadic ALS. In order to further elucidate the molecular
      mechanisms underlying SigR1-mediated alterations in sporadic and familial ALS, we
      extended our previous studies using neuronal SigR1 knockdown cell lines. We found
      that loss of SigR1 leads to abnormal ER morphology, mitochondrial abnormalities
      and impaired autophagic degradation. Consistent with these results, we found that
      endosomal trafficking of EGFR is impaired upon SigR1 knockdown. Furthermore, in
      SigR1-deficient cells the transport of vesicular stomatitis virus glycoprotein is
      inhibited, leading to the accumulation of this cargo protein in the Golgi
      apparatus. Moreover, depletion of SigR1 destabilized lipid rafts and associated
      calcium mobilization, confirming the crucial role of SigR1 in lipid raft and
      intracellular calcium homeostasis. Taken together, our results support the notion
      that loss of SigR1 function contributes to ALS pathology by causing abnormal ER
      morphology, lipid raft destabilization and defective endolysosomal pathways. 

PMID- 24922075
TI  - Bcl-xL controls a switch between cell death modes during mitotic arrest.
AB  - Antimitotic agents such as microtubule inhibitors (paclitaxel) are widely used in
      cancer therapy while new agents blocking mitosis onset are currently in
      development. All these agents impose a prolonged mitotic arrest in cancer cells
      that relies on sustained activation of the spindle assembly checkpoint and may
      lead to subsequent cell death by incompletely understood molecular events. We
      have investigated the role played by anti-apoptotic Bcl-2 family members in the
      fate of mitotically arrested mammary tumor cells treated with paclitaxel, or
      depleted in Cdc20, the activator of the anaphase promoting complex. Under these
      conditions, a weak and delayed mitotic cell death occurs that is caspase- and
      Bax/Bak-independent. Moreover, BH3 profiling assays indicate that viable cells
      during mitotic arrest are primed to die by apoptosis and that Bcl-xL is required
      to maintain mitochondrial integrity. Consistently, Bcl-xL depletion, or treatment
      with its inhibitor ABT-737 (but not with the specific Bcl-2 inhibitor ABT-199),
      during mitotic arrest converts cell response to antimitotics to efficient caspase
      and Bax-dependent apoptosis. Apoptotic priming under conditions of mitotic arrest
      relies, at least in part, on the phosphorylation on serine 62 of Bcl-xL, which
      modulates its interaction with Bax and its sensitivity to ABT-737. The phospho
      mimetic S62D-Bcl-xL mutant is indeed less efficient than the corresponding
      phospho-deficient S62A-Bcl-xL mutant in sequestrating Bax and in protecting
      cancer cells from mitotic cell death or yeast cells from Bax-induced growth
      inhibition. Our results provide a rationale for combining Bcl-xL targeting to
      antimitotic agents to improve clinical efficacy of antimitotic strategy in cancer
      therapy. 

PMID- 24922078
TI  - Defect in HSP90 expression in highly differentiated human CD8(+) T lymphocytes.

PMID- 24922080
TI  - Interindividual differences in attentional control profiles among younger and
      older adults.
AB  - This study aimed at characterizing the individual variability in three
      attentional control functions (shifting, inhibition, and updating), among 75
      older and 75 younger adults. It also examined the intellectual and health
      variables associated with different cognitive profiles. Cluster analyses
      identified three separate attentional control profiles for both age groups, but
      the patterns of variability were strikingly different. Younger adults' profiles
      were characterized by homogeneous performance across domains and differed only in
      their overall level of performance. In contrast, older adults' profiles were
      characterized by uneven levels of performance across domains and inhibition stood
      out as critical in distinguishing between profiles. One subgroup of older adults
      had poor inhibition and more adverse lifestyle characteristics and appeared more
      cognitively vulnerable. In conclusion, subgroups of younger and older adults with
      different attentional control profiles can be identified, but the expression of
      variability changes with age as older adults' profiles become more heterogeneous.

PMID- 24922081
TI  - Innopsy 2007.

PMID- 24922076
TI  - Augmentation of NAD(+) by NQO1 attenuates cisplatin-mediated hearing impairment.
AB  - Cisplatin (cis-diaminedichloroplatinum-II) is an extensively used
      chemotherapeutic agent, and one of its most adverse effects is ototoxicity. A
      number of studies have demonstrated that these effects are related to oxidative
      stress and DNA damage. However, the precise mechanism underlying cisplatin
      associated ototoxicity is still unclear. The cofactor nicotinamide adenine
      dinucleotide (NAD(+)) has emerged as a key regulator of cellular energy
      metabolism and homeostasis. Here, we demonstrate for the first time that, in
      cisplatin-mediated ototoxicity, the levels and activities of SIRT1 are suppressed
      by the reduction of intracellular NAD(+) levels. We provide evidence that the
      decrease in SIRT1 activity and expression facilitated by increasing poly(ADP
      ribose) transferase (PARP)-1 activation and microRNA-34a through p53 activation
      aggravates cisplatin-mediated ototoxicity. Moreover, we show that the induction
      of cellular NAD(+) levels using beta-lapachone (beta-Lap), whose intracellular
      target is NQO1, prevents the toxic effects of cisplatin through the regulation of
      PARP-1 and SIRT1 activity. These results suggest that direct modulation of
      cellular NAD(+) levels by pharmacological agents could be a promising therapeutic
      approach for protection from cisplatin-induced ototoxicity. 

PMID- 24922077
TI  - Identification of a natural product-like STAT3 dimerization inhibitor by
      structure-based virtual screening.
AB  - STAT3 regulates a variety of genes involved with cell proliferation,
      differentiation, apoptosis, angiogenesis, metastasis, inflammation, and immunity.
      The purpose of this study was to apply molecular docking techniques to identify
      STAT3 inhibitors from a database of over 90000 natural product and natural
      product-like compounds. The virtual screening campaign furnished 14 hit
      compounds, from which compound 1 emerged as a top candidate. Compound 1 inhibited
      STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription
      in cellulo with selectivity over STAT1 and with comparable potency to the well
      known STAT3 inhibitor S3I-201. Furthermore, compound 1 inhibited STAT3
      dimerization and decreased STAT3 phosphorylation in cells without affecting STAT1
      dimerization and phosphorylation. Compound 1 also exhibited selective anti
      proliferative activity against cancer cells over normal cells in vitro. Molecular
      docking analysis suggested that compound 1 might putatively function as an
      inhibitor of STAT3 dimerization by binding to the SH2 domain. This study also
      validates the use of in silico techniques to identify inhibitors of protein
      protein interactions, which are typically considered difficult to target with
      small molecules.

PMID- 24922082
TI  - Palladium-catalyzed oxidative cyclization of tertiary enamines for synthesis of
      1,3,4-trisubstituted pyrroles and 1,3-disubstituted indoles.
AB  - A novel and efficient palladium-catalyzed intramolecular oxidative cyclization of
      tertiary enamines for the synthesis of 1,3,4-trisubstituted pyrroles and 1,3
      disubstituted indoles has been developed. Trifluoroacetic acid plays an important
      role in the reaction. A series of pyrroles and indoles with substitution patterns
      that are not easily accessible by traditional routes were synthesized in good
      yields under mild conditions. 

PMID- 24922083
TI  - Micelle-induced versatile sensing behavior of bispyrene-based fluorescent
      molecular sensor for picric acid and PYX explosives.
AB  - The effect of surfactant micelles on the photophysical properties of a cationic
      bispyrene fluorophore, Py-diIM-Py, was systemically examined. The results from
      series of measurements including UV-vis absorption, steady-state fluorescence
      emission, quantum yield, fluorescence lifetime, and time-resolved emission
      spectra reveal that the cationic fluorophore is only encapsulated by the anionic
      sodium dodecyl sulfate (SDS) surfactant micelles and not incorporated in the
      cationic dodecyltrimethylammonium bromide (DTAB) and neutral Triton X-100 (TX100)
      surfactant micelles. This different fluorophore location in the micellar
      solutions significantly influences its sensing behavior to various explosives.
      Fluorescence quenching studies reveal that the simple variation of micellar
      systems leads to significant changes in the sensitivity and selectivity of the
      fluorescent sensor to explosives. The sensor exhibits an on-off response to
      multiple explosives with the highest sensitivity to picric acid (PA) in the
      anionic SDS micelles. In the cationic DTAB micelles, it displays the highest on
      off responses to PYX. Both the sensitivity and selectivity to PYX in the cationic
      micelles are enhanced compared with that to PA in the anionic micelles. However,
      the poor encapsulation in the neutral surfactant TX100 micelles leads to
      fluorescence instability of the fluorophore and fails to function as a sensor
      system. Time-resolved fluorescence decays in the presence of explosives reveal
      that the quenching mechanism of two micellar sensor systems to explosives is
      static in nature. The present work demonstrates that the electrostatic
      interaction between the cationic fluorophore and differently charged micelles
      plays a determinative role in adjusting its distribution in micellar solutions,
      which further influences the sensing behavior of the obtained micellar sensor
      systems. 

PMID- 24922084
TI  - Availability and use of molecular microbiological and immunological tests for the
      diagnosis of tuberculosis in europe.
AB  - INTRODUCTION: Currently only limited data exist regarding the availability and
      clinical use of molecular and immunological tests for tuberculosis (TB) in the
      European setting. METHODS: Web-based survey of Paediatric-Tuberculosis-Network
      European-Trialsgroup (ptbnet) and Tuberculosis-Network-European-Trialsgroup
      (TBnet) members conducted June to December 2013. Both networks comprise
      clinicians, microbiologists, epidemiologists and researchers predominately based
      in Europe. RESULTS: 191 healthcare professionals from 31 European countries
      participated. Overall, 26.8% of respondents did not have access to the Xpert
      MTB/RIF assay; only 44.6% had access to the assay in-house. However, a
      substantial proportion had access to other commercial and/or non-commercial PCR
      based assays for TB (68.8% and 31.8%, respectively). Only 6.4% did not have
      access to any PCR-based assays for TB. A large proportion of participants with
      access to the Xpert MTB/RIF assay had used it for the analysis of non-respiratory
      samples [pleural fluid: 36.5%, gastric aspirates: 34.7%, cerebrospinal fluid:
      34.7%, stool samples: 4.3%, blood/serum: 2.6%, 'other samples' (which included
      biopsy/tissue samples, lymph node aspirates, joint aspirates and urine samples):
      16.5%]. Regarding interferon-gamma release assays, a greater proportion of
      respondents had access to the QuantiFERON-TB Gold assay (84.7%) than to the T
      SPOT.TB assay (52.2%). CONCLUSIONS: Both immunological and molecular TB tests are
      widely available across Europe. The QuantiFERON-TB Gold assay is more widely used
      than the T-SPOT.TB assay, which may reflect the difficulties of integrating an
      ELISPOT assay into the routine laboratory setting. Although Xpert MTB/RIF assays
      are optimised and solely licensed for the analysis of sputum samples, in clinical
      practice they are commonly used for non-respiratory samples. Further research is
      needed to establish how current molecular TB tests impact on patient care and
      outcome in the routine clinical setting.

PMID- 24922085
TI  - Determination of plasma protein binding of positron emission tomography
      radioligands by high-performance frontal analysis.
AB  - Positron emission tomography (PET) is an imaging technique based on the use of
      radioligands labeled with short lived radionuclides, such as (11)C (t1/2=20.4min)
      and (18)F (t1/2=109.8min), which as a consequence often requires rapid plasma
      protein binding analysis methods. In addition, PET radioligands can suffer from
      non-specific binding to the membrane when ultrafiltraion, which is the most
      commonly used method for measuring protein binding in PET, is employed. In this
      study a high-performance frontal analysis (HPFA) method based on incorporation of
      a gel filtration column (discovery((r)) BIO GFC 100, 50mm*4.6mm, 5MUm, 100A) into
      a radio-LC system with phosphate buffered saline (PBS, pH 7.4) at a flow rate of
      3ml/min as mobile phase was developed and investigated for four PET radioligands.
      The minimum injection volume (MIV) of plasma, which is a crucial factor in HPFA,
      was determined to be 200MUl (human), 500MUl (monkey), 700MUl (human) and 1000MUl
      (monkey) for these four radioligands. The MIV values increased as a higher
      fraction of the radioligand was present in the protein-free form. The protein
      binding results obtained were in good agreement with ultrafiltration and the
      method did not suffer from non-specific binding. The short analysis time (<12min)
      allowed multiple protein binding measurements during time course of a human
      [(11)C]PBR28 PET study. 

PMID- 24922086
TI  - Structural elucidation of propoxyphenyl isobutyl aildenafil, adulterant in a
      health supplement using high-resolution Orbitrap mass spectrometry.
AB  - A new sildenafil analogue, propoxyphenyl isobutyl aildenafil has been found in
      trace quantity from one health supplement. It has been purified by preparative
      high performance liquid chromatography (HPLC). The structural elucidation of this
      compound has been carried out using high-resolution Orbitrap mass spectrometry
      under two fragmentation modes, namely High energy Collision Dissolution (HCD) and
      Collision Induced Dissolution (CID). Under MS(3) experiments and CID mode, the
      isobutyl-bonded fragments of propoxyphenyl isobutyl aildenafil at m/z 313 and 297
      have been compared with the reference ions derived from isobutyl sildenafil. The
      accurate mass measurement of each product ions has been carried out with the aid
      of Mass Frontier software (version 5.0). The mass error of all product ions is
      not more than 5.0ppm. 

PMID- 24922087
TI  - Atomic-scale wear of amorphous hydrogenated carbon during intermittent contact: a
      combined study using experiment, simulation, and theory.
AB  - In this study, we explore the wear behavior of amplitude modulation atomic force
      microscopy (AM-AFM, an intermittent-contact AFM mode) tips coated with a common
      type of diamond-like carbon, amorphous hydrogenated carbon (a-C:H), when scanned
      against an ultra-nanocrystalline diamond (UNCD) sample both experimentally and
      through molecular dynamics (MD) simulations. Finite element analysis is utilized
      in a unique way to create a representative geometry of the tip to be simulated in
      MD. To conduct consistent and quantitative experiments, we apply a protocol that
      involves determining the tip-sample interaction geometry, calculating the tip
      sample force and normal contact stress over the course of the wear test, and
      precisely quantifying the wear volume using high-resolution transmission electron
      microscopy imaging. The results reveal gradual wear of a-C:H with no sign of
      fracture or plastic deformation. The wear rate of a-C:H is consistent with a
      reaction-rate-based wear theory, which predicts an exponential dependence of the
      rate of atom removal on the average normal contact stress. From this, kinetic
      parameters governing the wear process are estimated. MD simulations of an a-C:H
      tip, whose radius is comparable to the tip radii used in experiments, making
      contact with a UNCD sample multiple times exhibit an atomic-level removal
      process. The atomistic wear events observed in the simulations are correlated
      with under-coordinated atomic species at the contacting surfaces. 

PMID- 24922088
TI  - Enhancing the electrical properties of a flexible transparent graphene-based
      field-effect transistor using electropolished copper foil for graphene growth.
AB  - Flexible transparent graphene-based field-effect transistors (Gr-FETs) were
      fabricated using large-area single-layer graphene synthesized through low
      pressure chemical vapor deposition on a pretreated copper (Cu) foil, followed by
      transfer of the graphene from the Cu foil to a poly(ethylene terephthalate) (PET)
      substrate. The electropolishing method was adopted to smooth the surface of the
      Cu foil, which is a crucial factor because it affects the defect density of
      graphene films on the PET substrate after transfer and the electronic transport
      property of the graphene-based devices. The influence of the electropolishing
      process on the graphene properties was examined using a Raman spectroscope, a
      scanning electron microscope, and an optical microscope. When the
      electropolishing process was adopted to improve the graphene quality, the carrier
      mobility of the flexible transparent Gr-FETs was enhanced from 90 to 340 cm(2)/(V
      s). Furthermore, variation of the carrier mobility was lower than 10% when the
      bending radius of the flexible device was decreased from 6.0 to 1.0 cm. 

PMID- 24922089
TI  - Pd-catalyzed carbonylation for the construction of tertiary and quaternary carbon
      centers with sp(3) carbon partners.
AB  - The first examples of a Pd-catalyzed carbonylation of aryl boronic acids with
      sp(3) carbon partners are presented. Various boronic acids were shown to react
      with 1,3-diesters and 1,3-diketones to afford structurally unique carbonyl
      compounds. By employing 2-substituted 1,3-diesters, synthetically-challenging
      quaternary carbon centres were accessed. In total, 42 examples of aryl carbonyl
      compounds were prepared in moderate to good yields. The catalytic system features
      the use of a bidentated phosphine ligand and a relatively low CO pressure (5
      atm), providing an easy, alternative method for the preparation of triketones. 

PMID- 24922090
TI  - Do self-assessed oral health and treatment need associate with clinical findings?
      Results from the Finnish Nationwide Health 2000 Survey.
AB  - OBJECTIVE: To associate self-assessed oral health and treatment need with
      clinically determined findings. MATERIALS AND METHODS: As part of the Finnish
      nationwide comprehensive Health 2000 Survey, the present cross-sectional study
      included dentate participants aged 30-64 years who self-assessed their oral
      health and treatment need in an interview and who underwent a clinical oral
      health examination (n = 4385). Self-assessed oral health and treatment need were
      used as subjective indicators. Clinically determined dental and periodontal
      status described objective dental and periodontal health and treatment need. The
      evaluation of relationships between subjective and objective findings was based
      on two-by-two tables and multivariate analyses. RESULTS: The better the self
      assessed oral health, the better the objective dental and periodontal health.
      Those reporting need for treatment more often had the objective need in terms of
      dental or periodontal treatment, also when controlling for background factors. Of
      the subjective indicators, good self-assessed oral health best reflected the
      absence of clinically determined dental or periodontal treatment need. Those who
      reported a need for treatment were mainly adults with an objective dental and
      periodontal treatment need. CONCLUSIONS: Self-assessed good oral health is a
      fairly good estimate for the absence of clinically determined dental and
      periodontal treatment need. As implication for practice, self-assessed data could
      be used for screening purposes for oral health service planning and for priority
      allocation in large adult populations.

PMID- 24922091
TI  - Individual changes in dental fear among children and parents: a longitudinal
      study.
AB  - OBJECTIVE: The aim was to study longitudinal changes in dental fear among
      children and one of their parents separately for girls, boys, mothers and fathers
      over a 3.5-year period. MATERIALS AND METHODS: 11-12-year-old children in Pori,
      Finland (n = 1691) and one of their parents were invited to participate in this
      longitudinal study. Dental fear was measured in 2001, 2003 and 2005 when the
      children were 11-12, 13-14 and 15-16-years-old, respectively. The participants
      were asked if they were afraid of dental care (1 = 'not afraid', 2 = 'slightly
      afraid', 3 = 'afraid to some degree', 4 = 'quite afraid', 5 = 'very afraid' and 6
      = 'I don't know'). The participants' gender was also registered. Mean values of
      the change scores were studied. Prevalence and incidence of dental fear and
      changes in dichotomized dental fear (responses 4-5 = high dental fear and
      responses 1-3 = low dental fear) were studied using cross-tabulations and
      Cochran's Q test. RESULTS: Overall, the prevalence of dental fear slightly
      increased and female preponderance in dental fear became more evident during the
      follow-up. Of the mothers and children with high dental fear at the baseline, 24%
      and 56%, respectively, reported not to be fearful at the end of the follow-up.
      CONCLUSIONS: Dental fear seems to be more stable in adulthood than in childhood.
      Thus, it might be better to intervene in dental fear during childhood rather than
      during adulthood.

PMID- 24922093
TI  - Awareness and perception of human papilloma virus vaccine among healthcare
      professionals in Nigeria.
AB  - Human papilloma virus (HPV) is a necessary cause of cervical cancer and cervical
      cancer is largely a vaccine-preventable disease. The aim of the study was to
      document the knowledge of healthcare professionals of the HPV vaccine and its
      acceptability. It was a cross-sectional study in three of the six geo-political
      zones of Nigeria, carried out between June 2010 and January 2011. The 602 adult
      Nigerian respondents were made up of 147 (24.4%) males and 455 (75.6%) females
      aged 20-57 years, with a mean of 34.3 +/- 7.9 years; most were under 40 years
      (70.1%) and married (n = 394; 65.5%). In total, 548 (91%) were aware of HPV;
      83.4% knew HPV as an STI; 78.2% knew HPV can cause cervical cancer but only 265
      (44.0%) were aware of the HPV vaccine. Among the healthcare professionals
      studied, nurses were the least aware of the existence of the HPV vaccine (chi(2)
      = 1.54, p = 0.001). A total of 489 (81.0%) would approve HPV vaccine for their
      teenage daughters. The men were more likely to accept the vaccination of their
      daughters than the women (chi(2) = 14.76, p = 0.002). The unmarried were more
      favourably disposed to vaccination of teenagers than the married (chi(2) = 27.37,
      p = 0.001). Safety concerns were the commonest reasons expressed by the 7% who
      were reluctant to accept the vaccination of their teenage daughters. In
      conclusion, healthcare providers are the custodians of health in a community, yet
      have low knowledge of a vaccine that can prevent the commonest cancer in women in
      sub-Saharan Africa.

PMID- 24922092
TI  - Influence of different drying methods on microtensile bond strength of self
      adhesive resin cements to dentin.
AB  - OBJECTIVE: This study investigated the effect of different drying methods of
      dentin surface on the bonding efficacy of self-adhesive resin cements (SRCs).
      MATERIALS AND METHODS: Three SRCs (RelyX U200, RU; Maxcem Elite, ME; and BisCem,
      BC) and one resin-modified glass ionomer cement (RelyX Luting 2, RL) were used.
      The characteristics of the materials were evaluated using thermogravimetric
      analysis and surface roughness and contact angle measurements. Human dentin
      surfaces were finished with 600-grit silicon carbide paper and assigned to three
      groups according to these drying methods: ethanol dehydration, drying by waiting
      for 10 s after blot-drying and blot-drying. The four cements were used for luting
      composite overlays to the dried dentin. After 24 h storage at 37 degrees C and
      100% relative humidity, stick-shaped specimens with a cross-sectional area of 0.8
      mm(2) were prepared and stressed to failure in tension at a crosshead speed of
      0.5 mm/min (n = 27). Failure modes of fractured specimens were assessed by
      optical and scanning electron microscopy. RESULTS: RL was the most hydrophilic,
      followed by BC and ME and then RU. All the luting cements luted to ethanol
      dehydrated dentin showed zero bond strengths. For the three SRCs, drying by
      waiting produced higher microtensile bond strengths than blot-drying. RU showed
      the best bonding performance in the above two dentin conditions. RL showed
      significantly higher bond strength in blot-drying condition than in drying-by
      waiting (p < 0.001). CONCLUSIONS: This study suggests that dentin surface
      moisture has a crucial effect on the bond strength of SRCs.

PMID- 24922094
TI  - Removal of uranium and gross radioactivity from coal bottom ash by CaCl2 roasting
      followed by HNO3 leaching.
AB  - A roast-leach method using CaCl2 and HNO3 to remove uranium and gross
      radioactivity in coal bottom ash was investigated. Heat treatment of the ash with
      100% CaCl2 (900 degrees C, 2h) significantly enhanced uranium leachability (>95%)
      compared with direct acid-leaching (22.6-25.5%). The removal efficiency of
      uranium and gross radioactivity increased steeply with increasing CaCl2 content,
      from 10% to 50%, and a HNO3 leaching time from 5 min to 1h, but remained nearly
      constant or decreased slightly with increasing CaCl2 dosage >50% or acid-leaching
      time >1h. The majority of the uranium (87.3%), gross alpha (92.9%) and gross beta
      (84.9%) were removed under the optimized roast-leach conditions (50% CaCl2, 1M
      HNO3 leaching for 1h). The mineralogical characteristics of roasted clinker
      indicated that molten CaCl2 promoted the incorporation of Ca into silica and
      silicates and resulted in its progressive susceptibility to acid attack. Uranium
      and other radionuclides, most likely present in the form of silicates or in
      association with miscellaneous silicates in the highest density fraction (>2.5g
      mL(-1)), were probably leached out as the result of the acid decomposition of
      newly formed "gelatinizing silicates".

PMID- 24922096
TI  - Quantitative assessment of the relationship between radiant heat exposure and
      protective performance of multilayer thermal protective clothing during dry and
      wet conditions.
AB  - The beneficial effect of clothing on a person is important to the criteria for
      people exposure to radiant heat flux from fires. The thermal protective
      performance of multilayer thermal protective clothing exposed to low heat fluxes
      during dry and wet conditions was studied using two designed bench-scale test
      apparatus. The protective clothing with four fabric layers (outer shell, moisture
      barrier, thermal linear and inner layer) was exposed to six levels of thermal
      radiation (1, 2, 3, 5, 7 and 10kW/m(2)). Two kinds of the moisture barrier (PTFE
      and GoreTex) with different vapor permeability were compared. The outside and
      inside surface temperatures of each fabric layer were measured. The fitting
      analysis was used to quantitatively assess the relationship between the
      temperature of each layer during thermal exposure and the level of external heat
      flux. It is indicated that there is a linear correlation between the temperature
      of each layer and the radiant level. Therefore, a predicted equation is developed
      to calculate the thermal insulation of the multilayer clothing from the external
      heat flux. It can also provide some useful information on the beneficial effects
      of clothing for the exposure criteria of radiant heat flux from fire. 

PMID- 24922095
TI  - Exposure to low dose benzo[a]pyrene during early life stages causes symptoms
      similar to cardiac hypertrophy in adult zebrafish.
AB  - Growing evidence indicates that polycyclic aromatic hydrocarbons (PAHs) can lead
      to cardiac hypertrophy and recent research indicates that exposure to low dose
      crude oil during early embryonic development may lead to impacts on heart health
      at later life stages. The aim of this study was to evaluate whether exposure
      during early life stages to low dose benzo[a]pyrene (BaP), as a high-ring PAH,
      would lead to cardiac hypertrophy at later life stages. Zebrafish were exposed to
      low dose BaP until 96 hpf, then transferred to clean water and maintained for a
      year before histological and molecular biological analysis. Our results showed
      that exposure to low level BaP during early life stages increased heart weight to
      body weight ratios and deposited collagen in the heart of adult zebrafish. ANP,
      BNP and c-Myc were also induced in the heart of adult zebrafish by BaP. These
      results proved that low level BaP exposure during early life stages caused
      symptoms similar to cardiac hypertrophy in adult zebrafish. Our results displayed
      an elevated expression of CdC42, RhoA, p-ERK1, 2 and Rac1. Therefore, the
      mechanism of the cardiac hypertrophy caused by BaP exposure during early life
      stages may be through inducing the expression of CdC42, RhoA and Rac1, together
      with activating ERK1, 2. 

PMID- 24922097
TI  - Arsenic uptake and depuration kinetics in Microcystis aeruginosa under different
      phosphate regimes.
AB  - Strategies used by Microcystis aeruginosa, bloom-forming cyanobacteria, for
      potential inorganic arsenic (arsenate and arsenite) uptake, and depuration
      kinetics under phosphate-enriched (+P) and depleted (-P) treatments were examined
      via short- and long-term experiments. Phosphate depletion improved arsenate or
      arsenite uptake rate constants. M. aeruginosa arsenite influx occurred
      considerably faster than arsenate influx under +P or -P treatments. Different
      phosphate regimes yielded significant impacts on long-term but not on short-term
      arsenic (As) uptake. In addition, considerable differences were observed in short
      term As efflux between live and dead cells after arsenate or arsenite pre
      exposure. Arsenic depuration rates in live M. aeruginosa cells were affected not
      only by accumulation rates of different As inorganic species but also by
      phosphate concentrations in tested media, which was inferred from estimated
      kinetic parameters. Specifically, +P was clearly found to inhibit As efflux after
      live M. aeruginosa cells were pre-exposed to As(V). Efflux was higher for dead
      cells no matter the inorganic As species involved. Owing to higher As uptake and
      depuration rates under -P treatments, P deficiency will considerably accelerate
      As uptake and efflux processes in aquatic environments. 

PMID- 24922098
TI  - Facile synthesis of porous single crystalline ZnO nanoplates and their
      application in photocatalytic reduction of Cr(VI) in the presence of phenol.
AB  - Porous single crystalline ZnO nanoplates were successfully synthesized through a
      facile and cost-effective hydrothermal process at low temperature condition,
      followed by annealing of the zinc carbonate hydroxide hydrate precursors. The as
      prepared products were characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer
      Emmett-Teller (BET) measurements. The porous single crystalline ZnO nanoplates
      are with 12nm thickness and pore ranging from 10nm to several tens of nanometers.
      The porous structure of the ZnO nanoplates caused large amount of surface defects
      which worked as photogenerated holes' shallow trappers and largely restrained the
      recombination of photogenerated electrons and holes, resulting in a significantly
      high photocatalytic activity and durability toward the photoreduction of Cr(VI)
      under UV irradiation. Moreover, a synergistic effect, that is, increased
      photocatalytic reduction of Cr(VI) and degradation of phenol, can be observed.
      Furthermore, the synergistic photocatalytic mechanism has also been discussed.
      Those results present an enlightenment to employ porous single crystalline
      nanomaterials to remove Cr(VI) and organic pollutants simultaneously. 

PMID- 24922099
TI  - The impact of health education transmitted via social media or text messaging on
      adolescent and young adult risky sexual behavior: a systematic review of the
      literature.
AB  - Despite the increased use of social media and text messaging among adolescents,
      it is unclear how effective education transmitted via these mechanisms is for
      reducing sexual risk behavior. Accordingly, we conducted a systematic review of
      the literature to examine the effectiveness of social media and text messaging
      interventions designed to increase sexually transmitted disease (STD) knowledge,
      increase screening/testing, decrease risky sexual behaviors, and reduce the
      incidence of STDs among young adults aged 15 through 24 years. Eleven studies met
      our inclusion criteria. Most of the included studies used a control group to
      explore intervention effects and included both young men and women. Sample sizes
      ranged from 32 to 7606 participants, and follow-up periods ranged between 4 weeks
      and 12 months. These studies provide preliminary evidence indicating that social
      media and text messaging can increase knowledge regarding the prevention of STDs.
      These interventions may also affect behavior, such as screening/testing for STDs,
      sexual risk behaviors, and STD acquisition, but the evidence for effect is weak.
      Many of these studies had several limitations that future research should
      address, including a reliance on self-reported data, small sample sizes, poor
      retention, low generalizability, and low analytic rigor. Additional research is
      needed to determine the most effective and engaging approaches for young men and
      women. 

PMID- 24922100
TI  - Topical application of trichloroacetic acid is efficacious for the treatment of
      internal anal high-grade squamous intraepithelial lesions in HIV-positive men.
AB  - OBJECTIVES: To assess the efficacy of topical 80% trichloroacetic acid (TCA) to
      treat internal anal high-grade squamous intraepithelial lesions (HSILs) in HIV
      positive individuals. METHODS: All patients who attended the University of
      Pittsburgh Anal Dysplasia Clinic for treatment of biopsy-proven internal anal
      HSIL with topical TCA between July 1, 2009, and June 30, 2012, and who had 1 or
      more follow-up visits to assess treatment efficacy were included in the analysis.
      Recurrence of HSIL was assessed in July 1, 2013. RESULTS: A total of 98 HSILs
      from 72 patients were treated, and 77 (78.6%) resolved to normal epithelium or
      low-grade SIL during follow-up. Forty-eight (49.0%) and 27 (27.6%) of lesions
      resolved with 1 and 2 TCA treatments, respectively, whereas 1 lesion (1%) each
      resolved with 3 and 4 TCA treatments. Twenty-one (21.4%) lesions in 20 patients
      remained without resolution after TCA treatments. These patients were offered an
      alternative treatment. During follow-up, 8 (15.1%) of 53 patients had a lesion
      that recurred at the index site (11/53 [20.8%], inclusive of adjacent lesions)
      and 17 patients had new lesions diagnosed. CONCLUSIONS: Topical TCA is an
      efficacious treatment of internal anal HSIL in an anal dysplasia clinic setting
      with high-resolution anoscopy capacity. Advantages of TCA for this recurrent
      disease process include the following: low cost, no requirement for special
      equipment beyond that for high-resolution anoscopy, and painless application
      procedure. A larger prospective comparative study would better define efficacy
      and patient acceptability between treatment methods.

PMID- 24922101
TI  - Associations of sexually transmitted infections with condom problems among young
      men who have sex with men.
AB  - BACKGROUND: Young men who have sex with men (YMSM) are disproportionately
      infected with sexually transmitted infections (STIs). Condom use is the most
      widely available means of preventing the transmission of STIs, but effectiveness
      depends on correct use. Condom errors such as using an oil-based lubricant have
      been associated with condom failures such as breakage. Little research has been
      done on the impact of condom problems on the likelihood of contracting an STI.
      METHODS: Data came from Crew 450, a longitudinal study of HIV risk among YMSM (N
      = 450). All self-report data were collected using computer-assisted self
      interview technology, and clinical testing was done for gonorrhea, chlamydia, and
      HIV. RESULTS: Nearly all participants made at least 1 error, with high rates of
      using oil-based lubricant and incomplete use. No differences were found in rates
      of condom problems during anal sex with a man versus vaginal sex with a woman.
      Black YMSM reported significantly higher use of oil-based lubricants than white
      and Hispanic YMSM, an error significantly associated with HIV status (adjusted
      odds ratio, 2.60; 95% confidence interval, 1.04-6.51). Participants who reported
      a condom failure were significantly more likely to have an STI (adjusted odds
      ratio, 3.27; 95% confidence interval, 1.31-8.12). CONCLUSIONS: Young men who have
      sex with men report high rates of condom problems, and condom failures were
      significantly associated with STIs after controlling for unprotected sex.
      Educational programs are needed to enhance correct condom use among YMSM. Further
      research is needed on the role of oil-based lubricants in explaining racial
      disparities in STIs and HIV.

PMID- 24922102
TI  - Multilevel risk factors for greater HIV infection of black men who have sex with
      men in New York City.
AB  - BACKGROUND: There is a large and disproportionate burden of HIV in black men who
      have sex with men (MSM) which is not adequately explained by racial/ethnic
      differences in risk behaviors. However, social factors may account for this
      disparity in HIV infection. We examine the extent to which both individual risk
      behaviors and social factors reduce the effect of black race and may account for
      the disparity in HIV infection of black MSM. METHODS: In a cross-sectional study
      in New York City in 2011, MSM were venue sampled, interviewed, and HIV tested.
      Variables associated (P < 0.10) both with black race and testing HIV positive
      were analyzed using multivariate logistic regression. RESULTS: Of 416
      participants who were HIV tested and did not self-report being positive, 19.5%
      were black, 41.1% were Hispanic, 30.5% were white, and 8.9% were of other
      race/ethnicity. Overall, 8.7% tested positive (24.7% of blacks, 7.6% of
      Hispanics, 1.0% of whites, and 5.4% of other). The effect of black race versus
      non-black race/ethnicity with testing HIV positive declined by 49.2%, (crude odds
      ratio, 6.5 [95% confidence interval, 3.2-13.3] vs. adjusted odds ratio, 3.3 [95%
      confidence interval, 1.5-7.5]), after adjustment for having a black last sex
      partner, not having tested for HIV in the past 12 months, Brooklyn residency, and
      having an annual income less than US$20,000. CONCLUSIONS: Greater HIV infection
      risk of black MSM may result from social factors and less frequent HIV testing
      than from differences in risk behaviors. To reduce the disparity in HIV infection
      of black MSM, multilevel interventions that both ameliorate social risk factors
      and increase the frequency of HIV testing are needed.

PMID- 24922103
TI  - Toll-like receptor polymorphisms are associated with increased neurosyphilis
      risk.
AB  - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR)
      1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We
      investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with
      laboratory- or clinically-defined neurosyphilis. METHODS: Polymorphisms in the
      genes for TLR1 (a T->G mutation at position 1805), TLR2 (a G->A mutation at
      position 2258), and TLR6 (a C->T mutation at position 745) were sought in 456
      white patients with syphilis. Laboratory-defined neurosyphilis included a
      reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL)
      test. Clinically-defined neurosyphilis included new vision or hearing loss.
      Controls had CSF white blood cells of 5/MUL or less, nonreactive CSF-Venereal
      Disease Research Laboratory, and no vision or hearing loss. RESULTS: Overall,
      26.2% of patients had laboratory-defined and 36.2% had clinically-defined
      neurosyphilis. Compared with controls, patients with any of the 3 SNPs were more
      likely to have laboratory-defined neurosyphilis. Those with TLR2 or TLR6 SNPs
      were more likely to have clinically-defined neurosyphilis. These associations
      were independent of serum rapid plasma reagin titer. CONCLUSIONS: A common TLR1
      polymorphism is associated with an increased risk of laboratory-defined
      neurosyphilis, and common TLR2 and TLR6 polymorphisms are associated with an
      increased risk of both laboratory- and clinically-defined neurosyphilis. These
      data suggest that host factors impact the natural history of syphilis.

PMID- 24922104
TI  - Incident sexually transmitted infection as a biomarker for high-risk sexual
      behavior after diagnosis of acute HIV.
AB  - BACKGROUND: Sexually transmitted infection (STI) diagnosis after diagnosis of
      acute HIV infection (AHI) indicates ongoing high-risk sexual behavior and
      possible risk of HIV transmission. We assessed predictors of STI acquisition and
      the effect of time since care entry on STI incidence in patients with AHI in care
      and receiving consistent risk-reduction messaging. METHODS: Data on incident
      gonorrhea, chlamydia, trichomoniasis, primary/secondary syphilis, demographic,
      and clinical risk factors were abstracted from medical charts for patients
      diagnosed as having AHI and engaged in care. Poisson regression models using
      generalized estimating equations were fit to estimate incidence rates (IRs), IR
      ratios, and robust 95% confidence intervals. RESULTS: Among 185 patients with
      AHI, 26 (14%) were diagnosed as having at least 1 incident STI over 709.4 person
      years; 46 STIs were diagnosed during follow-up (IR, 6.8/100 person-years). The
      median time from HIV care entry to first STI diagnosis was 609 days (range, 168
      1681 days). Men who have sex with men (P = 0.03), a shorter time between
      presentation to medical care and AHI diagnosis (P = 0.06), and STI diagnosis
      before AHI diagnosis (P = 0.0003) were predictors of incident STI. Sexually
      transmitted infection IR greater than 1 year after entering care was double that
      of patients in care 1 year or less (IR ratio, 2.0; 95% confidence interval, 0.8
      4.9). HIV viral load was above the limits of detection within 1 month of 11 STI
      diagnoses in 6 patients (23.1%) (median, 15,898 copies/mL; range, 244-152,000
      copies/mL). CONCLUSIONS: Despite regular HIV care, STI incidence was high among
      this primarily young, men who have sex with men AHI cohort. Early antiretroviral
      initiation may decrease HIV transmission given ongoing risk behaviors despite
      risk-reduction messaging.

PMID- 24922105
TI  - Periodic presumptive treatment for women with prevalent vaginal infections:
      secondary analysis of data from a randomized controlled trial.

PMID- 24922106
TI  - Translation of "at-home" HIV testing: response to Katz et al. and Hurt and
      Powers.

PMID- 24922107
TI  - Health reform and shifts in funding for sexually transmitted infection services.
AB  - BACKGROUND: In the Affordable Care Act era, no-cost-to-patient publicly funded
      sexually transmitted infection (STI) clinics have been challenged as the standard
      STI care delivery model. This study examined the impact of removing public
      funding and instituting a flat fee within an STI clinic under state-mandated
      insurance coverage. METHODS: Cross-sectional database analysis examined changes
      in visit volumes, demographics, and payer mix for 4 locations in Massachusetts'
      largest safety net hospital (STI clinic, primary care [PC], emergency department
      [ED], obstetrics/gynecology [OB/GYN] for 3 periods: early health reform
      implementation, reform fully implemented but public STI clinic funding retained,
      termination of public funding and institution of a US$75 fee in STI clinic for
      those not using insurance). RESULTS: Sexually transmitted infection visits
      decreased 20% in STI clinic (P < 0.001), increased 107% in PC (P < 0.001),
      slightly decreased in ED, and did not change in OB/GYN. The only large
      demographic shift observed was in the sex of PC patients--women comprised 51% of
      PC patients seen for STI care in the first time period, but rose sharply to 70%
      in the third time period (P < 0.0001). After termination of public funding, 50%
      of STI clinic patients paid flat fee, 35% used public insurance, and 15% used
      private insurance. CONCLUSIONS: Mandatory insurance, public funding loss, and
      institution of a flat STI clinic fee were associated with overall decreases in
      STI visit volume, with significant STI clinic visit decreases and PC STI visit
      increases. This may indicate partial shifting of STI services into PC. Half of
      STI clinic patients chose to pay the flat fee even after reform was fully
      implemented.

PMID- 24922108
TI  - Sexually transmitted disease clinics in the era of the affordable care act: is it
      time to tear down the walls?

PMID- 24922110
TI  - Advanced nanoarchitectures of silver/silver compound composites for photochemical
      reactions.
AB  - Silver/silver compound (SSC) composites have received much attention as a type of
      potential materials in photochemical reactions due to their high efficiency,
      facile syntheses and availability of raw materials. This article reviews the
      state-of-the-art progress on the advanced nanoarchitectures of SSC composites. We
      begin with a survey on the general synthetic strategies for SSC composites, and
      then step into relatively detailed methods for size and morphology tunable two
      component and more delicate multi-component SSC nanostructures. In addition, the
      electronic structure-related mechanisms of such materials and the recent studies
      on their stability are summarized. This review also highlights some perspectives
      on challenges related to the SSC composites and the possible research in the
      future. 

PMID- 24922109
TI  - Insurance and billing concerns among patients seeking free and confidential
      sexually transmitted disease care: New York City sexually transmitted disease
      clinics 2012.
AB  - BACKGROUND: Historically, New York City (NYC) Department of Health and Mental
      Hygiene (DOHMH) sexually transmitted disease (STD) clinics have operated
      completely free of charge but will soon begin billing patients for services. To
      inform billing strategies, we surveyed NYC DOHMH STD clinic patients in fall 2012
      to examine response to the prospect of billing insurance and charging sliding
      scale fees for services. METHODS: A total of 5017 individuals were surveyed from
      all patients accessing clinic services between September and December 2012 at 8
      NYC DOHMH STD clinics. The anonymous survey was provided at registration to all
      patients, in English or Spanish. The data were analyzed to determine patient
      insurance status and other characteristics related to billing for STD services.
      RESULTS: More than half of respondents (51.0%) were uninsured, and 42.3% were
      unemployed. For 20.2% of respondents, billing would pose a considerable barrier
      to care. Nearly half of those insured (48.4%) said that they would not be willing
      to share insurance information with the STD clinics. CONCLUSIONS: Respondents who
      said they would not access STD clinic services if charged represent approximately
      13,600 individuals each year who, if not promptly diagnosed and treated
      elsewhere, could be a continuing source of STIs including HIV. Confidentiality
      concerns and income are potential obstacles to billing insurance or charging a
      direct fee for STD services. New York City DOHMH plans to take the concerns
      raised in the survey findings into account when designing our billing system and
      carefully evaluate its impact to ensure that the need for accessible,
      confidential STD services continues to be met.

PMID- 24922111
TI  - The P1/P2 protein heterodimers assemble to the ribosomal stalk at the moment when
      the ribosome is committed to translation but not to the native 60S ribosomal
      subunit in Saccharomyces cerevisiae.
AB  - The four structural acidic ribosomal proteins that dissociate from P1A/P2B and
      P1B/P2A heterodimers of Saccharomyces cerevisiae were searched in the 60S
      ribosomal subunit, the 80S monosome, and the polysomal fractions after ribosome
      profile centrifugation in sucrose gradients in TMN buffer, and after dissociation
      of monosomes and polysomes to small and large ribosomal subunits in LMS buffer.
      Analysis by isoelectric focusing, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and Western blotting of these fractions or the purified acidic
      protein samples showed eight bands that correspond to the acidic ribosomal
      proteins in the 60S dissociated subunits of the 80S monosome and polysomes. After
      samples had been radiolabeled with (32)P, four bands were shown to correspond to
      the phosphorylated form of the acidic ribosomal proteins located in the 80S
      monosome and the polysomes. Surprisingly, native 60S subunits have no acidic
      ribosomal proteins. Altogether, these findings indicate that P1/P2 heterodimers
      bind to P0 when both ribosomal subunits are joined and committed to translation,
      and they detached from the stalk, just after the small and large ribosomal
      subunits were separated from the mRNA. Evidence that the phosphorylated and
      unphosphorylated P1 and P2 acidic ribosomal proteins are part of the functional
      stalk is also presented. 

PMID- 24922113
TI  - Antifouling coating with controllable and sustained silver release for long-term
      inhibition of infection and encrustation in urinary catheters.
AB  - Urinary tract infections constitute a large proportion of nosocomial infections,
      and the urinary catheter is the most important predisposing factor. Encrustation
      induced by urease-producing uropathogens like Proteus mirabilis causes further
      complications. In the present work, a strategy for controllable and sustained
      release of silver over several weeks has been developed for combating bacterial
      infection and encrustation in urinary devices. Silver nanoparticles (AgNPs) were
      first immobilized on polydopamine (PDA) pre-treated silicone catheter surface and
      this was followed by another PDA coating. The number of AgNP-PDA bilayers could
      be manipulated to control the amount of silver loaded and its subsequent release.
      Poly(sulfobetaine methacrylate-co-acrylamide) was then grafted to provide an
      antifouling outer layer, and to ensure free diffusion of Ag from the surface. The
      micron-scale combination of an antifouling coating with AgNP-PDA bilayers reduced
      colonization of the urinary catheter by uropathogens by approximately two orders
      of magnitude. With one and two AgNP-PDA bilayers, the coated catheter could
      resist encrustation for 12 and 45 days, respectively, compared with approximately
      6 days with the DoverTM silver-coated catheter. Such anti-infective and anti
      encrustation catheters can potentially have a large impact on reducing patient
      morbidity and healthcare expenditure.

PMID- 24922114
TI  - Immobility reaction at birth in newborn infant.
AB  - OBJECTIVE: To describe an immobility reaction (IR) that was not previously
      reported at or immediately after birth in human newborns. METHOD: We analyzed 31
      videos of normal term vaginal deliveries recorded from Time 0 of birth defined as
      the as the moment that lies between the birth of the thorax and the pelvis of the
      infant. We searched for perinatal factors associated with newborn's IR. RESULTS:
      IR at birth was observed in 8 of the 31 newborns. The main features of their
      behavior were immobilization, frozen face, shallow breathing and bradycardia. One
      of the 8 newborns had sudden collapse 2h after birth. We found significant
      relationships between maternal prenatal stress (PS) and IR (p=.037), and a close
      to significant one between infants' lividness at Time 0 and IR (p=.053). The
      first breath of the 31 newborns occurred before and was not associated with the
      first cry (p<.001). DISCUSSION: The main features of IR at birth are similar to
      those of the universal most severe response to severe stress or danger. The
      relationship with PS suggests that children who had IR at birth might be at risk
      for similar disorders as those associated with PS. Sudden neonatal collapse of
      one of the IR newborns needs further research to determine if they are at risk
      for sudden infant death syndrome. CONCLUSION: This first report of an IR reaction
      at birth in human infants could open up new paths for improving early neonatal
      care. Further research is needed for maternal PS, stress hormones, umbilical cord
      blood pH measurements in IR newborns. The challenge of education and support for
      parents of IR newborns is outlined.

PMID- 24922112
TI  - Cellular noise and information transmission.
AB  - The technological revolution in biological research, and in particular the use of
      molecular fluorescent labels, has allowed investigation of heterogeneity of
      cellular responses to stimuli on the single cell level. Computational,
      theoretical, and synthetic biology advances have allowed predicting and
      manipulating this heterogeneity with an exquisite precision previously reserved
      only for physical sciences. Functionally, this cell-to-cell variability can
      compromise cellular responses to environmental signals, and it can also enlarge
      the repertoire of possible cellular responses and hence increase the adaptive
      nature of cellular behaviors. And yet quantification of the functional importance
      of this response heterogeneity remained elusive. Recently the mathematical
      language of information theory has been proposed to address this problem. This
      opinion reviews the recent advances and discusses the broader implications of
      using information-theoretic tools to characterize heterogeneity of cellular
      behaviors. 

PMID- 24922115
TI  - The C-score: a Bayesian framework to sharply improve proteoform scoring in high
      throughput top down proteomics.
AB  - The automated processing of data generated by top down proteomics would benefit
      from improved scoring for protein identification and characterization of highly
      related protein forms (proteoforms). Here we propose the "C-score" (short for
      Characterization Score), a Bayesian approach to the proteoform identification and
      characterization problem, implemented within a framework to allow the infusion of
      expert knowledge into generative models that take advantage of known properties
      of proteins and top down analytical systems (e.g., fragmentation propensities,
      "off-by-1 Da" discontinuous errors, and intelligent weighting for site-specific
      modifications). The performance of the scoring system based on the initial
      generative models was compared to the current probability-based scoring system
      used within both ProSightPC and ProSightPTM on a manually curated set of 295
      human proteoforms. The current implementation of the C-score framework generated
      a marked improvement over the existing scoring system as measured by the area
      under the curve on the resulting ROC chart (AUC of 0.99 versus 0.78). 

PMID- 24922118
TI  - How disorder controls the kinetics of triplet charge recombination in
      semiconducting organic polymer photovoltaics.
AB  - Recent experiments by Rao et al. (Nature, 2013, 500, 435-439) indicate that
      recombination of triplet charge-separated states is suppressed in organic polymer
      fullerene based bulk-heterojunction (BHJ) photovoltaic cells exhibiting a high
      degree of crystallinity in the fullerene phase relative to systems with more
      disorder. In this paper, we use a series of Frenkel-exciton lattice models to
      rationalize these results in terms of wave-function localization, interface
      geometry, and density of states. In one-dimensional co-linear and co-facial
      models of the interface, increasing local energetic disorder in one phase
      localizes the interfacial triplet charge-transfer ((3)CT) states and increases
      the rate at which these states relax to form lower-energy triplet excitons. In
      two dimensional BHJ models, energetic disorder within the fullerene phase plays
      little role in further localizing states pinned to the interface. However,
      inhomogeneous broadening introduces strong coupling between the interfacial (3)CT
      and nearby fullerene triplet excitons and can enhance the decay of these states
      in systems with higher degrees of energetic disorder. 

PMID- 24922117
TI  - New symptom-based predictive tool for survival at seven and thirty days developed
      by palliative home care teams.
AB  - AIM: This study sought to develop models to predict survival at 7 and 30 days
      based on symptoms detected by palliative home care teams (PHCTs). MATERIALS AND
      METHODS: This prospective analytic study included a 6-month recruitment period
      with patient monitoring until death or 180 days after recruitment. The inclusion
      criteria consisted of age greater than 18 years, advanced cancer, and treatment
      provided by participating PHCTs between April and July 2009. The study variables
      included death at 7 or 30 days, survival time, age, gender, place of residence,
      type of tumor and extension, presence of 11 signs and symptoms measured with a 0
      3 Likert scale, functional and cognitive status, and use of a subcutaneous
      butterfly needle. The statistics applied included a descriptive analysis
      according to the percentage or mean+/-standard deviation. For symptom comparison
      between surviving and nonsurviving patients, the chi(2) test was used.
      Classification and regression tree (CART) methodology was used for model
      development. An internal validation system (cross-validation with 10 partitions)
      was used to ensure generalization of the models. The area under the receiver
      operating characteristics (ROC) curve was calculated (with a 95% confidence
      interval) to assess the validation of the models. RESULTS: A total of 698
      patients were included. The mean age of the patients was 73.7+/-12 years, and
      60.3% were male. The most frequent type of neoplasm was digestive (37.6%). The
      mean Karnofsky score was 51.8+/-14, the patients' cognitive status according to
      the Pfeiffer test was 2.6+/-4 errors, and 8.3% of patients required a
      subcutaneous butterfly needle. Each model provided 8 decision rules with a
      probability assignment range between 2.2% and 99.1%. The model used to predict
      the probability of death at 7 days included the presence of anorexia and
      dysphagia and the level of consciousness, and this model produced areas under the
      curve (AUCs) of 0.88 (0.86-0.90) and 0.81 (0.79-0.83). The model used to predict
      the probability of death at 30 days included the presence of asthenia and
      anorexia and the level of consciousness, and this model produced AUCs of 0.78
      (0.77-0.80) and 0.77 (0.75-0.79). CONCLUSION: For patients with advanced cancer
      treated by PHCTs, the use of classification schemes and decision trees based on
      specific symptoms can help clinicians predict survival at 7 and 30 days.

PMID- 24922119
TI  - Sedentary behaviour and social anxiety in obese individuals: the mediating role
      of body esteem.
AB  - Given that the prevalence of social anxiety in obese individuals is high, it is
      necessary that we increase our knowledge about the related factors that cause
      social anxiety in obese individuals. The present study sought to examine the role
      of body esteem as a mediator between sedentary behaviour and social anxiety. The
      participants were 207 overweight and obese individuals who completed the self
      report measures. The structural equation modelling displayed that obese
      individuals with sedentary behaviour and poor body esteem were more likely to
      show social anxiety. Body esteem partially mediated between sedentary behaviour
      and social anxiety. Our results highlight the role of sedentary behaviour and
      body esteem as promising avenues for reducing social anxiety in obese
      individuals. 

PMID- 24922120
TI  - Triple comorbid trajectories of tobacco, alcohol, and marijuana use as predictors
      of antisocial personality disorder and generalized anxiety disorder among urban
      adults.
AB  - OBJECTIVES: We modeled triple trajectories of tobacco, alcohol, and marijuana use
      from adolescence to adulthood as predictors of antisocial personality disorder
      (ASPD) and generalized anxiety disorder (GAD). METHODS: We assessed urban African
      American and Puerto Rican participants (n = 816) in the Harlem Longitudinal
      Development Study, a psychosocial investigation, at 4 time waves (mean ages = 19,
      24, 29, and 32 years). We used Mplus to obtain the 3 variable trajectories of
      tobacco, alcohol, and marijuana use from time 2 to time 5 and then conducted
      logistic regression analyses. RESULTS: A 5-trajectory group model, ranging from
      the use of all 3 substances (23%) to a nonuse group (9%), best fit the data.
      Membership in the trajectory group that used all 3 substances was associated with
      an increased likelihood of both ASPD (adjusted odds ratio [AOR] = 6.83; 95% CI =
      1.14, 40.74; P < .05) and GAD (AOR = 4.35; 95% CI = 1.63, 11.63; P < .001) in
      adulthood, as compared with the nonuse group, with control for earlier proxies of
      these conditions. CONCLUSIONS: Adults with comorbid tobacco, alcohol, and
      marijuana use should be evaluated for use of other substances and for ASPD, GAD,
      and other psychiatric disorders. Treatment programs should address the use of all
      3 substances to decrease the likelihood of comorbid psychopathology.

PMID- 24922121
TI  - Rules and values: a coordinated regulatory and educational approach to the public
      health crises of chronic pain and addiction.
AB  - Chronic pain and opioid addiction are 2 pressing public health problems, and
      prescribing clinicians often lack the skills necessary to manage these
      conditions. Our study sought to address the benefits of a coalition of an
      academic medical center pain faculty and government agencies in addressing the
      high unintentional overdose death rates in New Mexico. New Mexico's 2012-2013
      mandated chronic pain and addiction education programs studied more than 1000
      clinicians. Positive changes were noted in precourse and postcourse surveys of
      knowledge, self-efficacy, and attitudes. Controlled substance dispensing data
      from the New Mexico Board of Pharmacy also demonstrated safer prescribing. The
      total morphine and Valium milligram equivalents dispensed have decreased
      continually since 2011. There was also a concomitant decline in total drug
      overdose deaths. 

PMID- 24922122
TI  - The case for improving the health of ex-prisoners.
AB  - The global prison population exceeds 10 million and continues to grow; more than
      30 million people are released from custody annually. These individuals are
      disproportionately poor, disenfranchised, and chronically ill. There are
      compelling, evidence-based arguments for improving health outcomes for ex
      prisoners on human rights, public health, criminal justice, and economic grounds.
      These arguments stand in stark contrast to current policy and practice in most
      settings. There is also a dearth of evidence to guide clinicians and policymakers
      on how best to care for this large and growing population during and after their
      transition from custody to community. Well-designed longitudinal studies,
      clinical trials, and burden of disease studies are pivotal to closing this
      evidence gap. 

PMID- 24922123
TI  - Severe physical violence and Black women's health and well-being.
AB  - OBJECTIVES: We evaluated the association between intimate partner violence and
      the mental and physical health status of US Caribbean Black and African American
      women. METHODS: We used 2001 to 2003 cross-sectional data from the National
      Survey of American Life-the most detailed study to date of physical and mental
      health disorders of Americans of African descent. We assessed participants'
      health conditions by the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (Washington, DC; American Psychological Association) Composite
      International Diagnostic Interview. RESULTS: We found differences in health
      conditions between abused African American and Caribbean Black women. There were
      increased risks for lifetime dysthymia, alcohol dependence, drug abuse, and poor
      perceived health for African American victims of partner abuse, and binge eating
      disorder was associated with partner violence among Caribbean Black women.
      CONCLUSIONS: Severe intimate partner violence was associated with negative mental
      and physical health outcomes for US Black women, with different patterns between
      African American and Caribbean Blacks. Understanding intimate partner violence
      experiences of US Black women requires recognition of key intragroup differences,
      including nativity and immigrant status, and their differential relationships to
      women's health.

PMID- 24922124
TI  - Tobacco smoke incursions in multiunit housing.
AB  - OBJECTIVES: We sought to describe the prevalence of secondhand tobacco smoke
      incursions reported by multiunit housing (MUH) residents, pinpoint factors
      associated with exposure, and determine whether smoke-free building policy was
      associated with prevalence of reported tobacco smoke incursions. METHODS: Data
      are from a 2011 nationally representative dual-frame survey (random-digit-dial
      and Internet panels) of US adults aged 18 years and older. Individuals who lived
      in MUH and who reported no smoking in their homes for the past 3 months, whether
      or not they reported being smokers themselves, were included in this study.
      Incursions were defined as smelling tobacco smoke in their building or unit.
      RESULTS: Of 562 respondents, 29.5% reported smoke incursions in their buildings.
      Of these, 16% reported incursions in their own unit, 36.2% of which occurred at
      least weekly. Government-subsidized housing and partial smoke-free policies were
      associated with a higher likelihood of reporting smoke incursions. CONCLUSIONS:
      Many residents of multiunit housing are exposed to tobacco smoke in their units
      and buildings. Partial smoke-free policies do not appear to protect residents and
      might increase the likelihood of incursions in residents' individual units.

PMID- 24922125
TI  - The component model of infrastructure: a practical approach to understanding
      public health program infrastructure.
AB  - Functioning program infrastructure is necessary for achieving public health
      outcomes. It is what supports program capacity, implementation, and
      sustainability. The public health program infrastructure model presented in this
      article is grounded in data from a broader evaluation of 18 state tobacco control
      programs and previous work. The newly developed Component Model of Infrastructure
      (CMI) addresses the limitations of a previous model and contains 5 core
      components (multilevel leadership, managed resources, engaged data, responsive
      plans and planning, networked partnerships) and 3 supporting components
      (strategic understanding, operations, contextual influences). The CMI is a
      practical, implementation-focused model applicable across public health programs,
      enabling linkages to capacity, sustainability, and outcome measurement. 

PMID- 24922126
TI  - The interplay of friendship networks and social networking sites: longitudinal
      analysis of selection and influence effects on adolescent smoking and alcohol
      use.
AB  - OBJECTIVES: We examined the coevolution of adolescent friendships and peer
      influences with respect to their risk behaviors and social networking site use.
      METHODS: Investigators of the Social Network Study collected longitudinal data
      during fall 2010 and spring 2011 from 10th-grade students in 5 Southern
      California high schools (n = 1434). We used meta-analyses of stochastic actor
      based models to estimate changes in friendship ties and risk behaviors and the
      effects of Facebook and MySpace use. RESULTS: Significant shifts in adolescent
      smoking and drinking occurred despite little change in overall prevalence rates.
      Students with higher levels of alcohol use were more likely to send and receive
      friendship nominations and become friends with other drinkers. They were also
      more likely to increase alcohol use if their friends drank more. Adolescents
      selected friends with similar Facebook and MySpace use habits. Exposure to
      friends' risky online pictures increased smoking behaviors but had no significant
      effects on alcohol use. CONCLUSIONS: Our findings support a greater focus on
      friendship selection mechanisms in school-based alcohol use interventions. Social
      media platforms may help identify at-risk adolescent groups and foster positive
      norms about risk behaviors.

PMID- 24922127
TI  - Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D.
AB  - We examined the relationship between serum 25-hydroxyvitamin D (25[OH]D) and all
      cause mortality. We searched biomedical databases for articles that assessed 2 or
      more categories of 25(OH)D from January 1, 1966, to January 15, 2013. We
      identified 32 studies and pooled the data. The hazard ratio for all-cause
      mortality comparing the lowest (0-9 nanograms per milliliter [ng/mL]) to the
      highest (> 30 ng/mL) category of 25(OH)D was 1.9 (95% confidence interval = 1.6,
      2.2; P < .001). Serum 25(OH)D concentrations less than or equal to 30 ng/mL were
      associated with higher all-cause mortality than concentrations greater than 30
      ng/mL (P < .01). Our findings agree with a National Academy of Sciences report,
      except the cutoff point for all-cause mortality reduction in this analysis was
      greater than 30 ng/mL rather than greater than 20 ng/mL.

PMID- 24922128
TI  - Health literacy environmental scans of community-based dental clinics in
      Maryland.
AB  - OBJECTIVES: We conducted health literacy environmental scans in 26 Maryland
      community-based dental clinics to identify institutional characteristics and
      provider practices that affect dental services access and dental caries
      education. METHODS: In 2011-2012 we assessed user friendliness of the clinics
      including accessibility, signage, facility navigation, educational materials, and
      patient forms. We interviewed patients and surveyed dental providers about their
      knowledge and use of communication techniques. RESULTS: Of 32 clinics, 26
      participated. Implementation of the health literacy environmental scan tools was
      acceptable to the dental directors and provided clinic directors with information
      to enhance care and outreach. We found considerable variation among clinic
      facilities, operations, and content of educational materials. There was less
      variation in types of insurance accepted, no-show rates, methods of communicating
      with patients, and electronic health records use. Providers who had taken a
      communication skills course were more likely than those who had not to use
      recommended communication techniques. CONCLUSIONS: Our findings provide insight
      into the use of health literacy environmental scan tools to identify clinic and
      provider characteristics and practices that can be used to make dental
      environments more user friendly and health literate.

PMID- 24922129
TI  - Military service, exposure to trauma, and health in older adulthood: an analysis
      of northern Vietnamese survivors of the Vietnam War.
AB  - OBJECTIVES: We sought to better understand the association between early life
      exposure to war and trauma and older adult health status in a developing setting.
      METHODS: We analyzed data of 405 Vietnamese men and women in 1 northern Vietnam
      commune who entered early adulthood during the Vietnam War and who are now
      entering late adulthood (i.e., ages 55 years and older in 2010). RESULTS: The
      toll of war's trauma in the aging northern Vietnamese population was perceptible
      in the association between exposure to war trauma and various measures of
      physical health, including negative self-reported health and somatic symptoms.
      Killing another person and being exposed to toxic substances in warfare was
      especially detrimental to health in older adulthood. War traumas were likely
      implicated more strongly as determinants of late adulthood health in men than in
      women. The weak association between trauma exposure and reported depressive
      symptoms raised questions about measuring mental health. CONCLUSIONS: Military
      service and war trauma were important determinants of older adult health beyond
      the US context, given the widespread waging of war and concentration of recent
      armed conflicts within developing societies.

PMID- 24922130
TI  - A framework for describing health care delivery organizations and systems.
AB  - Describing, evaluating, and conducting research on the questions raised by
      comparative effectiveness research and characterizing care delivery organizations
      of all kinds, from independent individual provider units to large integrated
      health systems, has become imperative. Recognizing this challenge, the Delivery
      Systems Committee, a subgroup of the Agency for Healthcare Research and Quality's
      Effective Health Care Stakeholders Group, which represents a wide diversity of
      perspectives on health care, created a draft framework with domains and elements
      that may be useful in characterizing various sizes and types of care delivery
      organizations and may contribute to key outcomes of interest. The framework may
      serve as the door to further studies in areas in which clear definitions and
      descriptions are lacking. 

PMID- 24922131
TI  - Additional benefits of medical screening in a dental setting.

PMID- 24922132
TI  - Evolution and convergence of state laws governing controlled substance
      prescription monitoring programs, 1998-2011.
AB  - OBJECTIVES: We sought to collect and characterize all laws governing the
      operation of prescription monitoring programs (PMPs), state-level databases that
      collect patient-specific prescription information, which have been suggested as a
      tool for reducing prescription drug overdose fatalities. METHODS: We utilized a
      structured legal research protocol to systematically identify, review, and code
      all PMP statutes and regulations effective from 1998 through 2011. These laws
      were then abstracted along eleven domains, including reporting provisions, data
      sharing, and data access. RESULTS: PMP characteristics vary greatly among states
      and across time. We observed an increase in the types and frequency of data
      required to be reported, the types of individuals permitted to access PMP data,
      and the percentage of PMPs authorized to proactively identify outlier prescribers
      and patients. As of 2011, 10 states required PMPs to report suspicious activity
      to law enforcement, while only 3 required reporting to the patient's physician.
      None required linkage to drug treatment or required all prescribers to review PMP
      data before prescribing. Few explicitly address data retention. CONCLUSIONS:
      State PMP laws are heterogeneous and evolving. Future studies of PMP
      effectiveness should take these variations into account.

PMID- 24922133
TI  - Expanded access to naloxone among firefighters, police officers, and emergency
      medical technicians in Massachusetts.
AB  - Naloxone is a medication that reverses respiratory depression from opioid
      overdose if given in time. Paramedics routinely administer naloxone to opioid
      overdose victims in the prehospital setting, and many states are moving to
      increase access to the medication. Several jurisdictions have expanded naloxone
      administration authority to nonparamedic first responders, and others are
      considering that step. We report here on policy change in Massachusetts, where
      several communities have equipped emergency medical technicians, law enforcement
      officers, and firefighters with naloxone. 

PMID- 24922134
TI  - Educational disparities in the burden of disability: contributions of disease
      prevalence and disabling impact.
AB  - OBJECTIVES: We assessed the contributions of the prevalence and disabling impact
      of specific diseases to educational disparities in the prevalence of disability.
      METHODS: We examined a large representative survey of the Dutch population, the
      Dutch Permanent Survey of Living Conditions (2001-2007; n = 24 883; ages 40-97
      years). We attributed the prevalence of disability to chronic diseases by using
      their empirical associations and assuming independent competing causes of
      disability. We estimated contributions of prevalence and the disabling impact of
      diseases to disparities in disability using counterfactuals. RESULTS: We found
      that the prevalence of disability in individuals with only an elementary
      education was 19 to 20 percentage points higher than that in individuals with
      tertiary education. Sixty-five percent of this difference could be attributed to
      specific chronic diseases, but more so to their disabling impact (49%-51%) than
      to their prevalence (20%-29%). Back pain, neck or arm conditions, and peripheral
      vascular disease contributed most to the disparity in men, and arthritis, back
      pain, and chronic nonspecific lung disease contributed most to the disparity in
      women. CONCLUSIONS: Educational disparities in the burden of disability were
      primarily caused by high disabling impacts of chronic diseases among low educated
      groups. Tackling disparities might require more effective treatment or
      rehabilitation of disability in lower socioeconomic groups.

PMID- 24922135
TI  - Differences in time use and activity patterns when adding a second job:
      implications for health and safety in the United States.
AB  - OBJECTIVES: We compared work and lifestyle activities for workers who work in 1
      job with those who work in multiple jobs during a 1-week period. METHODS: We used
      information from the 2003-2011 American Time Use Survey to classify workers into
      6 work groups based on whether they were a single (SJH) or multiple (MJH) job
      holder and whether they worked their primary, other, multiple, or no job on the
      diary day. RESULTS: The MJHs often worked 2 part-time jobs (20%), long weekly
      hours (27% worked 60+ hours), and on weekends. The MJHs working multiple jobs on
      the diary day averaged more than 2 additional work hours (2.25 weekday, 2.75
      weekend day; P < .05), odd hours (more often between 5 pm and 7 am), with more
      work travel time (10 minutes weekday, 9 minutes weekend day; P < .05) and less
      sleep (-45 minutes weekday, -62 minutes weekend day; P < .05) and time for other
      household (P < .05) and leisure (P < .05) activities than SJHs. CONCLUSIONS:
      Because of long work hours, long daily commutes, multiple shifts, and less sleep
      and leisure time, MJHs may be at heightened risk of fatigue and injury.

PMID- 24922136
TI  - Traffic fatality reductions: United States compared with 25 other countries.
AB  - OBJECTIVES: I compared US traffic fatality trends with those in 25 other
      countries. METHODS: I have introduced a new measure for comparing safety in
      different countries: traffic deaths in a specific year relative to largest annual
      number recorded. I used only data from the International Road Traffic Accident
      Database. RESULTS: The United States is a unique outlier. Fatalities in all 25
      other countries declined further after reaching their maximum values. For
      example, the United States and the Netherlands both reached maximum values in
      1972. From 1972 to 2011 US deaths declined by 41%, whereas those in the
      Netherlands declined by 81%. If US fatalities had declined by 81% there would
      have been 22 000 fewer US road deaths in 2011. If the United States matched
      percentage declines of 6 additional countries, US deaths would have declined by
      more than 20 000. CONCLUSIONS: If US traffic deaths had declined by the same
      percentage as in any 1 of 7 other countries, more than 20 000 fewer Americans
      would have been killed in 2011.

PMID- 24922137
TI  - Industry actors, think tanks, and alcohol policy in the United kingdom.
AB  - Corporate actors seek to influence alcohol policies through various means,
      including attempts to shape the evidential content of policy debates. In this
      case study, we examined how SABMiller engaged the think tank Demos to produce
      reports on binge drinking, which were heavily promoted among policymakers at
      crucial stages in the development of the UK government's 2012 alcohol strategy.
      One key report coincided with other SABMiller-funded publications, advocating
      measures to enhance parenting as an alternative to minimum unit pricing. In this
      instance, the perceived independence of an influential think tank was used to
      promote industry interests in tactics similar to those of transnational tobacco
      corporations. This approach is in keeping with other alcohol industry efforts to
      marginalize the peer-reviewed literature. 

PMID- 24922139
TI  - Brockmann et al. respond.

PMID- 24922140
TI  - Twenty thousand more Americans killed annually because US traffic-safety policy
      rejects science.

PMID- 24922138
TI  - Determinants of increased opioid-related mortality in the United States and
      Canada, 1990-2013: a systematic review.
AB  - We review evidence of determinants contributing to increased opioid-related
      mortality in the United States and Canada between 1990 and 2013. We identified 17
      determinants of opioid-related mortality and mortality increases that we
      classified into 3 categories: prescriber behavior, user behavior and
      characteristics, and environmental and systemic determinants. These determinants
      operate independently but interact in complex ways that vary according to
      geography and population, making generalization from single studies inadvisable.
      Researchers in this area face significant methodological difficulties; most of
      the studies in our review were ecological or observational and lacked control
      groups or adjustment for confounding factors; thus, causal inferences are
      difficult. Preventing additional opioid-related mortality will likely require
      interventions that address multiple determinants and are tailored to specific
      locations and populations. 

PMID- 24922141
TI  - Intervention model for contaminated consumer products: a multifaceted tool for
      protecting public health.
AB  - Lead-based paint and occupational lead hazards remain the primary exposure
      sources of lead in New York City (NYC) children and men, respectively. Lead
      poisoning has also been associated with the use of certain consumer products in
      NYC. The NYC Department of Health and Mental Hygiene developed the Intervention
      Model for Contaminated Consumer Products, a comprehensive approach to identify
      and reduce exposure to lead and other hazards in consumer products. The model
      identifies hazardous consumer products, determines their availability in NYC,
      enforces on these products, and provides risk communication and public education.
      Implementation of the model has resulted in removal of thousands of contaminated
      products from local businesses and continues to raise awareness of these
      hazardous products. 

PMID- 24922142
TI  - Effects of lowering the minimum alcohol purchasing age on weekend assaults
      resulting in hospitalization in New Zealand.
AB  - OBJECTIVES: We estimated the effects on assault rates of lowering the minimum
      alcohol purchasing age in New Zealand from 20 to 18 years. We hypothesized that
      the law change would increase assaults among young people aged 18 to 19 years
      (the target group) and those aged 15 to 17 years via illegal sales or alcohol
      supplied by older friends or family members. METHODS: Using Poisson regression,
      we examined weekend assaults resulting in hospitalization from 1995 to 2011.
      Outcomes were assessed separately by gender among young people aged 15 to 17
      years and those aged 18 to 19 years, with those aged 20 and 21 years included as
      a control group. RESULTS: Relative to young men aged 20 to 21 years, assaults
      increased significantly among young men aged 18 to 19 years between 1995 and 1999
      (the period before the law change), as well as the postchange periods 2003 to
      2007 (incidence rate ratio [IRR] = 1.21; 95% confidence interval [CI] = 1.05,
      1.39) and 2008 to 2011 (IRR = 1.20; 95% CI = 1.05, 1.37). Among boys aged 15 to
      17 years, assaults increased during the postchange periods 1999 to 2003 (IRR =
      1.28; 95% CI = 1.10, 1.49) and 2004 to 2007 (IRR = 1.25; 95% CI = 1.08, 1.45).
      There were no statistically significant effects among girls and young women.
      CONCLUSIONS: Lowering the minimum alcohol purchasing age increased weekend
      assaults resulting in hospitalization among young males 15 to 19 years of age.

PMID- 24922143
TI  - Community mobilization and empowerment of female sex workers in Karnataka State,
      South India: associations with HIV and sexually transmitted infection risk.
AB  - OBJECTIVES: We examined the impact of community mobilization (CM) on the
      empowerment, risk behaviors, and prevalence of HIV and sexually transmitted
      infection in female sex workers (FSWs) in Karnataka, India. METHODS: We conducted
      behavioral-biological surveys in 2008 and 2011 in 4 districts of Karnataka,
      India. We defined exposure to CM as low, medium (attended nongovernmental
      organization meeting or drop-in centre), or high (member of collective or peer
      group). We used regression analyses to explore whether exposure to CM was
      associated with the preceding outcomes. Pathway analyses explored the degree to
      which effects could be attributable to CM. RESULTS: By the final survey, FSWs
      with high CM exposure were more likely to have been tested for HIV (adjusted odd
      ratio [AOR] = 25.13; 95% confidence interval [CI] = 13.07, 48.34) and to have
      used a condom at last sex with occasional clients (AOR = 4.74; 95% CI =  2.17,
      10.37), repeat clients (AOR = 4.29; 95% CI = 2.24, 8.20), and regular partners
      (AOR = 2.80; 95% CI = 1.43, 5.45) than FSWs with low CM exposure. They were also
      less likely to be infected with gonorrhea or chlamydia (AOR = 0.53; 95% CI =
      0.31, 0.87). Pathway analyses suggested CM acted above and beyond peer education;
      reduction in gonorrhea or chlamydia was attributable to CM. CONCLUSIONS: CM is a
      central part of HIV prevention programming among FSWs, empowering them to better
      negotiate condom use and access services, as well as address other concerns in
      their lives.

PMID- 24922144
TI  - Adolescent immunization coverage and implementation of new school requirements in
      Michigan, 2010.
AB  - OBJECTIVES: We examined the effect of Michigan's new school rules and vaccine
      coadministration on time to completion of all the school-required vaccine series,
      the individual adolescent vaccines newly required for sixth grade in 2010, and
      initiation of the human papillomavirus (HPV) vaccine series, which was
      recommended but not required for girls. METHODS: Data were derived from the
      Michigan Care Improvement Registry, a statewide Immunization Information System.
      We assessed the immunization status of Michigan children enrolled in sixth grade
      in 2009 or 2010. We used univariable and multivariable Cox regression models to
      identify significant associations between each factor and school completeness.
      RESULTS: Enrollment in sixth grade in 2010 and coadministration of adolescent
      vaccines at the first adolescent visit were significantly associated with
      completion of the vaccines required for Michigan's sixth graders. Children
      enrolled in sixth grade in 2010 had higher coverage with the newly required
      adolescent vaccines by age 13 years than did sixth graders in 2009, but there was
      little difference in the rate of HPV vaccine initiation among girls. CONCLUSIONS:
      Education and outreach efforts, particularly regarding the importance and
      benefits of coadministration of all recommended vaccines in adolescents, should
      be directed toward health care providers, parents, and adolescents.

PMID- 24922146
TI  - Self, medicated.

PMID- 24922145
TI  - Tobacco retailer proximity and density and nicotine dependence among smokers with
      serious mental illness.
AB  - OBJECTIVES: We examined the density and proximity of tobacco retailers and
      associations with smoking behavior and mental health in a diverse sample of 1061
      smokers with serious mental illness (SMI) residing in the San Francisco Bay Area
      of California. METHODS: Participants' addresses were geocoded and linked with
      retailer licensing data to determine the distance between participants' residence
      and the nearest retailer (proximity) and the number of retailers within 500-meter
      and 1-kilometer service areas (density). RESULTS: More than half of the sample
      lived within 250 meters of a tobacco retailer. A median of 3 retailers were
      within 500 meters of participants' residences, and a median of 12 were within 1
      kilometer. Among smokers with SMI, tobacco retailer densities were 2-fold greater
      than for the general population and were associated with poorer mental health,
      greater nicotine dependence, and lower self-efficacy for quitting. CONCLUSIONS:
      Our findings provide further evidence of the tobacco retail environment as a
      potential vector contributing to tobacco-related disparities among individuals
      with SMI and suggest that this group may benefit from progressive environmental
      protections that restrict tobacco retail licenses and reduce aggressive point-of
      sale marketing.

PMID- 24922147
TI  - Associations of adolescent hopelessness and self-worth with pregnancy attempts
      and pregnancy desire.
AB  - OBJECTIVES: We examined the associations of pregnancy desire (ambivalence or
      happiness about a pregnancy in the next year) and recent pregnancy attempts with
      hopelessness and self-worth among low-income adolescents. METHODS: To evaluate
      independent associations among the study variables, we conducted gender
      stratified multivariable logistic regression analyses with data derived from 2285
      sexually experienced 9- to 18-year-old participants in the Mobile Youth Survey
      between 2006 and 2009. RESULTS: Fifty-seven percent of youths reported a desire
      for pregnancy and 9% reported pregnancy attempts. In multivariable analyses,
      hopelessness was positively associated and self-worth was negatively associated
      with pregnancy attempts among both female and male youths. Hopelessness was
      weakly associated (P = .05) with pregnancy desire among female youths.
      CONCLUSIONS: The negative association of self-worth and the positive association
      of hopelessness with pregnancy attempts among young men as well as young women
      and the association of hopelessness with pregnancy desire among young women raise
      questions about why pregnancy is apparently valued by youths who rate their
      social and cognitive competence as low and who live in an environment with few
      options for material success.

PMID- 24922148
TI  - State Medicaid expansion, community interventions, and health care disparities in
      a United States-Mexico border community.
AB  - OBJECTIVES: We investigated whether access to and use of health care services
      increased among residents of a low-income, predominantly Mexican American border
      community affected by the expansion of Arizona's Medicaid program in 2001 and
      multiple community-level programs and policies. METHODS: We used data from a
      probability sample of 1623 adult residents of Douglas, Arizona, who participated
      in cross-sectional health surveys in 1998 and 2010. Response rates were 83% and
      86%, respectively. RESULTS: In 2010, participants were more likely to have a
      usual source of care, to have visited a provider in the previous year, and to
      have been screened for diabetes and hypertension and less likely to have delayed
      needed care or to have seen a regular provider in Mexico (P < .001 for all
      outcomes). Improvements in access to and use of health care were most pronounced
      among residents with less than a high school education, which reduced or
      eliminated educational disparities in health care. CONCLUSIONS: Expansion of
      public insurance programs can effectively reduce health care disparities when
      paired with other community-level policies and programs that target medically
      underserved populations.

PMID- 24922149
TI  - Impact of state cigarette taxes on disparities in maternal smoking during
      pregnancy.
AB  - OBJECTIVES: We evaluated the impact of state tobacco control policies on
      disparities in maternal smoking during pregnancy. METHODS: We analyzed 2000-2010
      National Vital Statistics System natality files with 17 699 534 births from 28
      states and the District of Columbia that used the 1989 revision of the birth
      certificate. We conducted differences-in-differences regression models to assess
      whether changes in cigarette taxes and smoke-free legislation were associated
      with changes in maternal smoking during pregnancy and number of cigarettes
      smoked. To evaluate disparities, we included interaction terms between maternal
      race/ethnicity, education, and cigarette taxes. RESULTS: Although maternal
      smoking decreased from 11.6% to 8.9%, White and Black women without a high school
      degree had some of the highest rates of smoking (39.7% and 16.4%, respectively).
      These same women were the most responsive to cigarette tax increases, but not to
      smoke-free legislation. For every $1.00 cigarette tax increase, low-educated
      White and Black mothers decreased smoking by nearly 2 percentage points and
      smoked between 14 and 22 fewer cigarettes per month. CONCLUSIONS: State cigarette
      taxes may be an effective population-level intervention to decrease racial/ethnic
      and socioeconomic disparities in maternal smoking during pregnancy.

PMID- 24922150
TI  - Public bicycle share programs and head injuries.
AB  - OBJECTIVES: We evaluated the effect of North American public bicycle share
      programs (PBSPs), which typically do not offer helmets with rentals, on the
      occurrence of bicycle-related head injuries. METHODS: We analyzed trauma center
      data for bicycle-related injuries from 5 cities with PBSPs and 5 comparison
      cities. We used logistic regression models to compare the odds that admission for
      a bicycle-related injury would involve a head injury 24 months before PBSP
      implementation and 12 months afterward. RESULTS: In PBSP cities, the proportion
      of head injuries among bicycle-related injuries increased from 42.3% before PBSP
      implementation to 50.1% after (P < .01). This proportion in comparison cities
      remained similar before (38.2%) and after (35.9%) implementation (P = .23). Odds
      ratios for head injury were 1.30 (95% confidence interval = 1.13, 1.67) in PBSP
      cities and 0.94 (95% confidence interval = 0.79, 1.11) in control cities
      (adjusted for age and city) when we compared the period after implementation to
      the period before. CONCLUSIONS: Results suggest that steps should be taken to
      make helmets available with PBSPs. Helmet availability should be incorporated
      into PBSP planning and funding, not considered an afterthought following
      implementation.

PMID- 24922151
TI  - Impact of texting laws on motor vehicular fatalities in the United States.
AB  - Using a panel study design, we examined the effects of different types of texting
      bans on motor vehicular fatalities. We used the Fatality Analysis Reporting
      System and a difference-in-differences approach to examine the incidence of fatal
      crashes in 2000 through 2010 in 48 US states with and without texting bans. Age
      cohorts were constructed to examine the impact of these bans on age-specific
      traffic fatalities. Primarily enforced laws banning all drivers from texting were
      significantly associated with a 3% reduction in traffic fatalities in all age
      groups, and those banning only young drivers from texting had the greatest impact
      on reducing deaths among those aged 15 to 21 years. Secondarily enforced
      restrictions were not associated with traffic fatality reductions in any of our
      analyses. 

PMID- 24922152
TI  - The next generation of users: prevalence and longitudinal patterns of tobacco use
      among US young adults.
AB  - OBJECTIVES: We monitored the prevalence and patterns of use of the array of
      tobacco products available to young adults, who are at risk for initiation and
      progression to established tobacco use. METHODS: We used data from waves 1 to 3
      of GfK's KnowledgePanel (2011-2012), a nationally representative cohort of young
      adults aged 18 to 34 years (n = 2144). We examined prevalence and patterns of
      tobacco product use over time, associated demographics, and state-level tobacco
      policy. We used multivariable logistic regression to determine predictors of
      initiation of cigarettes as well as noncombustible and other combustible
      products. RESULTS: The prevalence of ever tobacco use rose from 57.28% at wave 1
      to 67.43% at wave 3. Use of multiple products was the most common pattern (66.39%
      of tobacco users by wave 3). Predictors of initiation differed by product type
      and included age, race/ethnicity, policy, and use of other tobacco products.
      CONCLUSIONS: Tobacco use is high among young adults and many are using multiple
      products. Efforts to implement policy and educate young adults about the risks
      associated with new and emerging products are critical to prevent increased
      initiation of tobacco use.

PMID- 24922153
TI  - Sources of racial/ethnic differences in awareness of HIV vaccine trials.
AB  - OBJECTIVES: We explored the relative effects of 2 awareness components-exposure
      and attention-on racial/ethnic differences in HIV vaccine trial awareness among
      men who have sex with men (MSM). METHODS: Surveys assessing awareness of and
      attitudes toward HIV vaccine trials were administered to 1723 MSM in 6 US cities.
      Proxy measures of exposure included use of HIV resources and other health care
      services, community involvement, income, and residence. Attention proxy measures
      included research attitudes, HIV susceptibility, and HIV message fatigue. Using
      logistic regression models, we assessed the extent to which these proxies
      accounted for racial/ethnic differences in vaccine trial awareness. RESULTS:
      White MSM reported significantly (P < .01) higher rates of HIV vaccine trial
      awareness (22%) compared with Latino (17%), Black (13%) and "other" (13%) MSM.
      Venue-based exposure proxies and research-directed attitudinal attention proxies
      were significantly associated with awareness, but only accounted for the White
      Latino disparity in awareness. No proxies accounted for the White-Black or White
      "other" differentials in awareness. CONCLUSIONS: Sources of disparities in
      awareness of HIV vaccine trials remain to be explained. Future trials seeking to
      promote diverse participation should explore additional exposure and attention
      mediators.

PMID- 24922154
TI  - Prevalence, harm perceptions, and reasons for using noncombustible tobacco
      products among current and former smokers.
AB  - OBJECTIVES: We provided estimates of noncombustible tobacco product (electronic
      nicotine delivery systems [ENDS]; snus; chewing tobacco, dip, or snuff; and
      dissolvables) use among current and former smokers and examined harm perceptions
      of noncombustible tobacco products and reasons for their use. METHODS: We
      assessed awareness of, prevalence of, purchase of, harm perceptions of, and
      reasons for using noncombustible tobacco products among 1487 current and former
      smokers from 8 US designated market areas. We used adjusted logistic regression
      to identify correlates of noncombustible tobacco product use. RESULTS: Of the
      sample, 96% were aware of at least 1 noncombustible tobacco product, but only 33%
      had used and 21% had purchased one. Noncombustible tobacco product use was
      associated with being male, non-Hispanic White, younger, and more nicotine
      dependent. Respondents used noncombustible tobacco products to cut down or quit
      cigarettes, but only snus was associated with a higher likelihood of making a
      quit attempt. Users of noncombustible tobacco products, particularly ENDS, were
      most likely to endorse the product as less harmful than cigarettes. CONCLUSIONS:
      Smokers may use noncombustible tobacco products to cut down or quit smoking.
      However, noncombustible tobacco product use was not associated with a reduction
      in cigarettes per day or cessation.

PMID- 24922155
TI  - Termination of medicaid policies and implications for the Affordable Care Act.

PMID- 24922156
TI  - Language and stigmatization in addiction medicine.

PMID- 24922157
TI  - Latent tuberculosis infection screening in foreign-born populations: a successful
      mobile clinic outreach model.
AB  - OBJECTIVES: We evaluated the efficacy of a mobile medical clinic (MMC) screening
      program for detecting latent tuberculosis infection (LTBI) and active
      tuberculosis. METHODS: A LTBI screening program in a MMC in New Haven,
      Connecticut, used medical surveys to examine risk factors and tuberculin skin
      test (TST) screening eligibility. We assessed clinically relevant correlates of
      total (prevalent; n = 4650) and newly diagnosed (incident; n = 4159) LTBI from
      2003 to 2011. RESULTS: Among 8322 individuals, 4159 (55.6%) met TST screening
      eligibility criteria, of which 1325 (31.9%) had TST assessed. Similar to LTBI
      prevalence (16.8%; 779 of 4650), newly diagnosed LTBI (25.6%; 339 of 1325) was
      independently correlated with being foreign-born (adjusted odds ratio [AOR] =
      8.49; 95% confidence interval [CI] = 5.54, 13.02), Hispanic (AOR = 3.12; 95% CI =
      1.88, 5.20), Black (AOR = 2.16; 95% CI = 1.31, 3.55), employed (AOR = 1.61; 95%
      CI = 1.14, 2.28), and of increased age (AOR = 1.04; 95% CI = 1.02, 1.05).
      Unstable housing (AOR = 4.95; 95% CI = 3.43, 7.14) and marijuana use (AOR = 1.57;
      95% CI = 1.05, 2.37) were significantly correlated with incident LTBI, and being
      male, heroin use, interpersonal violence, employment, not having health
      insurance, and not completing high school were significantly correlated with
      prevalent LTBI. CONCLUSIONS: Screening for TST in MMCs successfully identifies
      high-risk foreign-born, Hispanic, working, and uninsured populations and
      innovatively identifies LTBI in urban settings.

PMID- 24922158
TI  - Evaluating the effect of state regulation of federally licensed firearm dealers
      on firearm homicide.
AB  - Effective federal regulation of firearm dealers has proven difficult.
      Consequently, many states choose to implement their own regulations. We examined
      the impact of state-required licensing, record keeping of sales, allowable
      inspections, and mandatory theft reporting on firearm homicide from 1995 to 2010.
      We found that lower homicide rates were associated with states that required
      licensing and inspections. We concluded that firearm dealer regulations might be
      an effective harm reduction strategy for firearm homicide. 

PMID- 24922159
TI  - Discrimination and substance use disorders among Latinos: the role of gender,
      nativity, and ethnicity.
AB  - OBJECTIVES: We examined the relationship between discrimination and substance use
      disorders among a diverse sample of Latinos. We also investigated whether the
      relationship between discrimination and substance use disorders varied by gender,
      nativity, and ethnicity. METHODS: Our analyses focused on 6294 Latinos who
      participated in the National Epidemiologic Survey on Alcohol and Related
      Conditions from 2004 to 2005. We used multinomial logistic regression to examine
      the association between discrimination and substance use disorders. RESULTS:
      Discrimination was significantly associated with increased odds of alcohol and
      drug use disorders among Latinos. However, the relationship between
      discrimination and substance use disorders varied by gender, nativity, and
      ethnicity. Discrimination was associated with increased odds of alcohol and drug
      use disorders for certain groups, such as women, US-born Latinos, and Mexicans,
      but this relationship did not follow the same pattern for other subgroups.
      CONCLUSIONS: It is important to determine which subgroups among Latinos may be
      particularly vulnerable to the negative effects of discrimination to address
      their needs.

PMID- 24922160
TI  - Primary prevention of lead poisoning: protecting children from unsafe housing.
AB  - OBJECTIVES: We examined the effects of changes in Rhode Island's Lead Hazard
      Mitigation Law in 2005 on children's blood lead levels. METHODS: We used 2005 to
      2009 data from Rhode Island's Lead Elimination Surveillance System; city tax
      assessor records in Central Falls, Pawtucket, Providence, and Woonsocket, Rhode
      Island; and records of conformance to the state's lead hazard mitigation law, to
      assess the extent to which legislation changes resulted in minimizing children's
      exposure to lead. RESULTS: During the 5-year study, the proportion of properties
      that complied with the new law increased for properties that housed young
      children. However, the majority of rental properties did not comply with the law.
      Children's lead levels declined by approximately 1 microgram per deciliter on
      average in properties that did comply, demonstrating that the law could have a
      protective effect for children. CONCLUSIONS: Legislation changes increased the
      proportion of properties that were certified as nonhazardous, leading to
      decreased blood lead levels for children living in these properties. However,
      legislation cannot be a highly effective primary prevention strategy if it does
      not cover all properties where children live and is not strictly enforced.

PMID- 24922161
TI  - The impact of data suppression on local mortality rates: the case of CDC WONDER.
AB  - CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data
      for Epidemiologic Research) is the nation's primary data repository for health
      statistics. Before WONDER data are released to the public, data cells with fewer
      than 10 case counts are suppressed. We showed that maps produced from suppressed
      data have predictable geographic biases that can be removed by applying
      population data in the system and an algorithm that uses regional rates to
      estimate missing data. By using CDC WONDER heart disease mortality data, we
      demonstrated that effects of suppression could be largely overcome. 

PMID- 24922162
TI  - Effects of the It's Your Game . . . Keep It Real program on dating violence in
      ethnic-minority middle school youths: a group randomized trial.
AB  - OBJECTIVES: We examined whether It's Your Game . . . Keep It Real (IYG) reduced
      dating violence among ethnic-minority middle school youths, a population at high
      risk for dating violence. METHODS: We analyzed data from 766 predominantly ethnic
      minority students from 10 middle schools in southeast Texas in 2004 for a group
      randomized trial of IYG. We estimated logistic regression models, and the primary
      outcome was emotional and physical dating violence perpetration and victimization
      by ninth grade. RESULTS: Control students had significantly higher odds of
      physical dating violence victimization (adjusted odds ratio [AOR] = 1.52; 95%
      confidence interval [CI] = 1.20, 1.92), emotional dating violence victimization
      (AOR = 1.74; 95% CI = 1.36, 2.24), and emotional dating violence perpetration
      (AOR = 1.58; 95% CI = 1.11, 2.26) than did intervention students. The odds of
      physical dating violence perpetration were not significantly different between
      the 2 groups. Program effects varied by gender and race/ethnicity. CONCLUSIONS:
      IYG significantly reduced 3 of 4 dating violence outcomes among ethnic-minority
      middle school youths. Although further study is warranted to determine if IYG
      should be widely disseminated to prevent dating violence, it is one of only a
      handful of school-based programs that are effective in reducing adolescent dating
      violence behavior.

PMID- 24922163
TI  - Missed opportunity for alcohol problem prevention among army active duty service
      members postdeployment.
AB  - OBJECTIVES: We identified to what extent the Department of Defense postdeployment
      health surveillance program identifies at-risk drinking, alone or in conjunction
      with psychological comorbidities, and refers service members who screen positive
      for additional assessment or care. METHODS: We completed a cross-sectional
      analysis of 333 803 US Army active duty members returning from Iraq or
      Afghanistan deployments in fiscal years 2008 to 2011 with a postdeployment health
      assessment. Alcohol measures included 2 based on self-report quantity-frequency
      items-at-risk drinking (positive Alcohol Use Disorders Identification Test
      alcohol consumption questions [AUDIT-C] screen) and severe alcohol problems
      (AUDIT-C score of 8 or higher)-and another based on the interviewing provider's
      assessment. RESULTS: Nearly 29% of US Army active duty members screened positive
      for at-risk drinking, and 5.6% had an AUDIT-C score of 8 or higher. Interviewing
      providers identified potential alcohol problems among only 61.8% of those
      screening positive for at-risk drinking and only 74.9% of those with AUDIT-C
      scores of 8 or higher. They referred for a follow-up visit to primary care or
      another setting only 29.2% of at-risk drinkers and only 35.9% of those with AUDIT
      C scores of 8 or higher. CONCLUSIONS: This study identified missed opportunities
      for early intervention for at-risk drinking. Future research should evaluate the
      effect of early intervention on long-term outcomes.

PMID- 24922164
TI  - Preconception stress, birth weight, and birth weight disparities among US women.
AB  - OBJECTIVES: We examined the impact of preconception acute and chronic stressors
      on offspring birth weight and racial/ethnic birth weight disparities. METHODS: We
      included birth weights for singleton live first (n = 3512) and second (n = 1901)
      births to White, Mexican-origin Latina, other-origin Latina, and Black women
      reported at wave IV of the National Longitudinal Study of Adolescent Health (2007
      2008; ages 24-32 years). We generated factor scores for preconception acute and
      chronic stressors from wave I (1994-1995; ages 11-19 years) or wave III (2001
      2002; ages 18-26 years) for the same cohort of women. RESULTS: Linear regression
      models indicated that chronic stressors, but not acute stressors, were inversely
      associated with birth weight for both first and second births (b = -192; 95%
      confidence interval = -270, -113; and b = -180; 95% confidence interval = -315, 
      45, respectively), and partially explained the disparities in birth weight
      between the minority racial/ethnic groups and Whites. CONCLUSIONS: Preconception
      chronic stressors contribute to restricted birth weight and to racial/ethnic
      birth weight disparities.

PMID- 24922165
TI  - Socioeconomic disparities in telephone-based treatment of tobacco dependence.
AB  - OBJECTIVES: We examined socioeconomic disparities in tobacco dependence treatment
      outcomes from a free, proactive telephone counseling quitline. METHODS: We
      delivered cognitive-behavioral treatment and nicotine patches to 6626 smokers and
      examined socioeconomic differences in demographic, clinical, environmental, and
      treatment use factors. We used logistic regressions and generalized estimating
      equations (GEE) to model abstinence and account for socioeconomic differences in
      the models. RESULTS: The odds of achieving long-term abstinence differed by
      socioeconomic status (SES). In the GEE model, the odds of abstinence for the
      highest SES participants were 1.75 times those of the lowest SES participants.
      Logistic regression models revealed no treatment outcome disparity at the end of
      treatment, but significant disparities 3 and 6 months after treatment.
      CONCLUSIONS: Although quitlines often increase access to treatment for some lower
      SES smokers, significant socioeconomic disparities in treatment outcomes raise
      questions about whether current approaches are contributing to tobacco-related
      socioeconomic health disparities. Strategies to improve treatment outcomes for
      lower SES smokers might include novel methods to address multiple factors
      associated with socioeconomic disparities.

PMID- 24922166
TI  - Changes in experiences with discrimination across pregnancy and postpartum: age
      differences and consequences for mental health.
AB  - OBJECTIVES: We aimed to contribute to growing research and theory suggesting the
      importance of examining patterns of change over time and critical life periods to
      fully understand the effects of discrimination on health, with a focus on the
      period of pregnancy and postpartum and mental health outcomes. METHODS: We used
      hierarchical linear modeling to examine changes across pregnancy and postpartum
      in everyday discrimination and the resulting consequences for mental health among
      predominantly Black and Latina, socioeconomically disadvantaged young women who
      were receiving prenatal care in New York City. RESULTS: Patterns of change in
      experiences with discrimination varied according to age. Among the youngest
      participants, discrimination increased from the second to third trimesters and
      then decreased to lower than the baseline level by 1 year postpartum; among the
      oldest participants, discrimination decreased from the second trimester to 6
      months postpartum and then returned to the baseline level by 1 year postpartum.
      Within-subjects changes in discrimination over time predicted changes in
      depressive and anxiety symptoms at subsequent points. Discrimination more
      strongly predicted anxiety symptoms among participants reporting food insecurity.
      CONCLUSIONS: Our results support a life course approach to understanding the
      impact of experiences with discrimination on health and when to intervene.

PMID- 24922167
TI  - Transition to adulthood and antiretroviral adherence among HIV-positive young
      Black men who have sex with men.
AB  - OBJECTIVES: We conducted a qualitative study of HIV-positive young Black men who
      have sex with men (YBMSM) to explore their experiences of living with HIV and
      adhering to antiretroviral medications (ARVs) within the developmental context of
      their transition to adulthood. METHODS: We conducted life history interviews with
      20 HIV-positive YBMSM in Atlanta, Georgia, engaged in outpatient HIV care. We
      addressed these questions: (1) How do YBMSM living with HIV experience the
      transition to adulthood? and (2) What are the important sociocontextual
      influences on ARV adherence for YBMSM? RESULTS: Successful transition to
      adulthood and optimal ARV adherence were inextricably linked. HIV's detrimental
      impact on development was moderated by the degree of physical illness at
      diagnosis. Many participants described resilient trajectories while coping with
      HIV. Adherence problems occurred primarily among participants who were not
      meeting their developmental goals. CONCLUSIONS: Our findings support the need for
      early diagnosis and linkage to care, as well as the need to develop holistic,
      resilience-based interventions focusing on transition to adulthood. These
      findings have implications for individual clinical outcomes as well as ARV-based
      prevention efforts among YBMSM.

PMID- 24922168
TI  - Estimating the proportion of cases of lung cancer legally attributable to
      smoking: a novel approach for class actions against the tobacco industry.
AB  - OBJECTIVES: The plaintiffs' lawyers for a class action suit, which was launched
      in Quebec on behalf of all patients with lung cancer whose disease was caused by
      cigarette smoking, asked us to estimate what proportion of lung cancer cases in
      Quebec, if they hypothetically could be individually evaluated, would satisfy the
      criterion that it is "more likely than not" that smoking caused the disease.
      METHODS: The novel methodology we developed is based on the dose-response
      relationship between smoking and lung cancer, for which we use the pack-years as
      a measure of smoking, and the distribution of pack-years of smoking among cases.
      RESULTS: We estimated that the amount of smoking required to satisfy the "more
      likely than not" criterion is between 3 and 11 pack-years. More than 90% of the
      Quebec cases satisfied even the most conservative of these thresholds.
      CONCLUSIONS: More than 90% of cases of lung cancer in Quebec are legally
      attributable to smoking. The methodology enhances the ability to conduct class
      action suits against the tobacco industry.

PMID- 24922169
TI  - Mortality from sexually transmitted diseases in reproductive-aged women: United
      States, 1999-2010.
AB  - OBJECTIVES: I estimated the sexually transmitted disease-related mortality among
      US reproductive-aged women from 1999 to 2010. METHODS: I estimated mortality from
      National Center for Health Statistics' Multiple Cause of Death data. I defined
      reproductive age as 15 to 44 years. For diseases partially caused by sexual
      transmission, I estimated the proportion attributable to sexual transmission from
      the literature. To calculate mortality rates, I estimated number of deaths from
      each disease and Census Bureau population for reproductive-aged women for 1999 to
      2010. RESULTS: From 1999 to 2010, the cumulative sexually transmitted disease
      related mortality rate decreased by 49%, from 5.3 to 2.7 deaths per 100 000. The
      primary contributors were HIV and human papilloma virus infections. Mortality
      from sexually transmitted HIV infection decreased by 62%, from 3.4 to 1.3 deaths
      per 100 000. Mortality from human papilloma virus-associated gynecologic cancers
      decreased by 19%, from 1.6 deaths per 100 000 in 1999 to 1.3 deaths per 100 000
      in 2010. CONCLUSIONS: Screening and treatment for sexually transmitted diseases
      may reduce mortality. Research is needed to determine whether sexually
      transmitted disease-related morbidity among reproductive-aged women has decreased
      over the past decade.

PMID- 24922170
TI  - Self-management: a comprehensive approach to management of chronic conditions.
AB  - For both clinical and economic reasons, the increasing number of persons living
      with chronic conditions represents a public health issue of growing importance.
      Emphasizing patient responsibility, and acting in concert with the provider
      community, self-management represents a promising strategy for treating chronic
      conditions-moving beyond education to teaching individuals to actively identify
      challenges and solve problems associated with their illness. Self-management also
      shows potential as an effective paradigm across the prevention spectrum (primary,
      secondary, and tertiary) by establishing a pattern for health early in life and
      providing strategies for mitigating illness and managing it in later life. We
      suggest ways to advance research methods and practical applications of self
      management as steps in its future development and implementation. 

PMID- 24922171
TI  - Women's health and the Affordable Care Act: high hopes versus harsh realities?
AB  - Our population-based survey of 1078 randomly sampled US women, aged 18 to 55
      years, sought to characterize their understanding of and attitudes toward the
      Affordable Care Act (ACA). Most women, especially socially disadvantaged groups,
      had negative or uncertain attitudes toward the ACA and limited understanding of
      its health benefits, including its relevance for their own health service
      coverage and utilization. Our findings are important for continued research,
      policy, and practice, with implications for whether, when, and how improved
      coverage will translate to improved access and outcomes for US women. 

PMID- 24922172
TI  - A comparison of cessation counseling received by current smokers at US dentist
      and physician offices during 2010-2011.
AB  - OBJECTIVES: We compared patient-reported receipt of smoking cessation counseling
      from US dentists and physicians. METHODS: We analyzed the 2010 to 2011 Tobacco
      Use Supplement of the Current Population Survey to assess receipt of smoking
      cessation advice and assistance by a current smoker from a dentist or physician
      in the past 12 months. RESULTS: Current adult smokers were significantly less
      likely to be advised to quit smoking during a visit to a dentist (31.2%) than to
      a physician (64.8%). Among physician patients who were advised to quit, 52.7%
      received at least 1 form of assistance beyond the simple advice to quit; 24.5% of
      dental patients received such assistance (P < .05). Approximately 9.4 million
      smokers who visited a dentist in 2010 to 2011 did not receive any cessation
      counseling. CONCLUSIONS: Our results indicate a need for intensified efforts to
      increase dentist involvement in cessation counseling. System-level changes,
      coupled with regular training, may enhance self-efficacy of dentists in engaging
      patients in tobacco cessation counseling.

PMID- 24922173
TI  - Transient childhood psychosis after upper respiratory infection.
AB  - Two cases of psychosis after upper respiratory infection were reported. New
      mental illness among children was substantiated after analyzing the cause of
      psychosis during the past 10 years of practice. It is confirmed that there is an
      association between psychosis and upper respiratory infection. 

PMID- 24922174
TI  - Fat content and composition in retail samples of Australian beef mince.
AB  - Nutrient composition data, representative of the retail supply, is required to
      support labelling and dietetic practice. Because beef mince represents
      approximately 30% of all beef dishes prepared in Australian households, a
      national survey of the different types of mince available for purchase in
      representative retail outlets was conducted. Sixty-one samples of beef mince from
      24 retail outlets in New South Wales, Queensland, Victoria and Western Australia
      were collected in 2010 and analysed for moisture, protein, total fat and fatty
      acid profile. A variety of 18 different descriptors were used at point of sale
      with "Premium" (n = 15) and "Regular" (n = 8) the most commonly used terms. The
      analysed fat content of "Premium" samples varied from 2.2 g/100 g to 8.0 g/100 g.
      Forty-eight percent (n = 29) of the samples were categorised as low fat (<5 g/100
      g; mean 4.1 g/100 g), 21% as medium fat (5-10 g/100 g; mean 8.9 g/100 g) and 31%
      as high fat (>10 g/100 g; mean 10.4 g/100 g). There was no significant difference
      between the types of mince available for purchase in low versus high socio
      economic suburbs (Chi-square, p > 0.05). In conclusion, the fat content of the
      majority of retail beef mince in Australia is <10 g/100 g and a variety of
      descriptors are used at point of sale, all of which do not necessarily reflect
      analysed fat content. 

PMID- 24922175
TI  - Zinc fortification decreases ZIP1 gene expression of some adolescent females with
      appropriate plasma zinc levels.
AB  - Zinc homeostasis is achieved after intake variation by changes in the expression
      levels of zinc transporters. The aim of this study was to evaluate dietary intake
      (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and
      the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc
      importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24
      adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc
      intake increased (p < 0.001) from 10.5 +/- 3.9 mg/day to 17.6 +/- 4.4 mg/day, and
      its estimated absorption from 3.1 +/- 1.2 to 5.3 +/- 1.3 mg/day. Mean plasma zinc
      concentration remained unchanged (p > 0.05) near 150 ug/dL, but increased by 31
      ug/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 ug/dL (p <
      0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood
      leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression
      of ZnT1 there was no difference after intervention (p = 0.39). An increase of
      dietary zinc after 27-days consumption of fortified-milk did not increase (p >
      0.05) the plasma level of adolescent girls but for 6/24 participants from group A
      in spite of the formerly appropriation, which cellular zinc uptake decreased as
      assessed by reduction of the expression of ZIP1. 

PMID- 24922176
TI  - Ordered carbon nanotubes-n-dodecyl tetraethylene monoether liquid crystal
      composites through phase separation induced by poly(ethylene glycol).
AB  - Carbon nanotubes (CNTs) were incorporated into a lyotropic liquid crystal (LLC)
      matrix at room temperature through spontaneous phase separation. The phase
      separation process occurred in n-dodecyl tetraethylene monoether (C12E4)
      solutions induced by the hydrophilic polymer, poly(ethylene glycol) (PEG). It was
      found that the molecular weight of PEG has a significant effect on the CNTs-C12E4
      system, which not only influences the phase behavior of the system but also
      changes the properties of the CNTs-LLC composites. Polarized optical microscopy
      (POM) images, combined with small-angle X-ray scattering (SAXS) results, indicate
      that CNTs incorporate within the layers of the lamellar LLCs without destroying
      the structure of LLCs. Moreover, UV-vis absorption, Raman spectra and rheological
      measurements were performed to investigate the characteristic properties of the
      CNTs-LLC composites. This study not only gives a more comprehensive understanding
      of polymer-induced phase separation, but also expands the potential uses of CNTs
      LLC composites in nanotechnology. 

PMID- 24922178
TI  - Gd(DOTAlaP): exploring the boundaries of fast water exchange in gadolinium-based
      magnetic resonance imaging contrast agents.
AB  - Here, we describe the synthesis of the single amino acid chelator DOTAlaP and
      four of its derivatives. The corresponding gadolinium(III) complexes were
      investigated for their kinetic inertness, relaxometric properties at a range of
      fields and temperatures, water exchange rate, and interaction with human serum
      albumin (HSA). Derivatives with one inner-sphere water (q = 1) were determined to
      have a mean water residency time between 8 and 6 ns in phoshate-buffered saline
      at 37  degrees C. The corresponding europium complexes were also formed and used
      to obtain information on the hydration number of the corresponding coordination
      complexes. Two complexes capable of binding HSA were also synthesized, of which
      one, Gd(5b), contains no inner-sphere water, while the other derivative, Gd(4b),
      is a mixture of ca. 15% q =1 and 85% q = 0. In the presence of HSA, the latter
      displayed a very short mean water residency time (tauM(310) = 2.4 ns) and
      enhanced relaxivity at intermediate and high fields. The kinetic inertness of
      Gd(4b) with respect to complex dissociation was decreased compared to its DOTAla
      analogue but still 100-fold more inert than [Gd(BOPTA)(H2O)](2-). Magnetic
      resonance imaging in mice showed that Gd(4b) was able to provide 38% better
      vessel to muscle contrast compared to the clinically used HSA binding agent MS
      325. 

PMID- 24922179
TI  - Drug development for pediatric neurogenic bladder dysfunction: dosing, endpoints,
      and study design.
AB  - Pediatric drug development is challenging when a product is studied for a
      pediatric disease that has a different underlying etiology and pathophysiology
      compared to the adult disease. Neurogenic bladder dysfunction (NBD) is such a
      therapeutic area with multiple unsuccessful development programs. The objective
      of this study was to critically evaluate clinical trial design elements that may
      have contributed to unsuccessful drug development programs for pediatric NBD.
      Trial design elements of drugs tested for pediatric NBD were identified from
      trials submitted to the U.S. Food and Drug Administration. Data were extracted
      from publically available FDA reviews and labeling and included trial design,
      primary endpoints, enrollment eligibilities, and pharmacokinetic data. A total of
      four products were identified. Although all four programs potentially provided
      clinically useful information, only one drug (oxybutynin) demonstrated efficacy
      in children with NBD. The lack of demonstrable efficacy for the remainder of the
      products illustrates that future trials should give careful attention to testing
      a range of doses, using objectively measured, clinically meaningful endpoints,
      and selecting clinical trial designs that are both interpretable and feasible.
      Compiling the drug development experience with pediatric NBD will facilitate an
      improved approach for future drug development for this, and perhaps other,
      therapeutic areas. 

PMID- 24922180
TI  - Controlled in situ fabrication of Ag2O/AgO thin films by a dry chemical route at
      room temperature for hybrid solar cells.
AB  - Silver oxides (Ag2O and AgO) have attracted increasing attention as potential
      solar cell materials for photovoltaic devices due to their ideal bandgap and non
      toxicity. In order to eliminate the complicated synthesis and harsh reaction
      conditions (e.g. high temperature, high vacuum, high energy input, electron beam
      instrumentation) required by most synthetic strategies, we developed a very
      facile dry chemical approach to directly prepare AgxO species on the ITO
      substrate by taking advantage of a UV-O3 surrounding in a controlled way. We
      systematically investigated the effects of relative humidity, reaction
      temperature, and the silver deposition technique on the formation of silver oxide
      (AgO or Ag2O) thin films. A possible synthetic mechanism for the formation of AgO
      and Ag2O is proposed. More importantly, we have designed and successfully
      fabricated novel inorganic hybrid Ag2O/Bi2O3 heterojunction thin films for the
      first time which exhibit significantly improved photocurrent compared with pure
      Bi2O3 films. 

PMID- 24922181
TI  - Levosulpiride in somatoform disorders: A double-blind, placebo-controlled cross
      over study.
AB  - Reliable data on the psychopharmacotherapy of somatoform disorders (SDs) are
      scanty because of patients' poor psychopathological awareness and compliance, the
      need for combination treatment, and the lack of suitable instruments for clinical
      diagnosis and assessment. The aim of the present study was to investigate the
      efficacy and tolerability of low doses of levosulpiride in the treatment of SDs.
      Seventy-four patients with SDs diagnosed according to ICD-10 and DSM-IIIR
      criteria by means of the Comprehensive International Schedule for Somatoform
      Disorders-Somatoform Disorders Schedule (CISSD-SDS) were treated for 4 weeks
      either with levosulpiride (50 mg b.i.d.) or placebo, under double-blind, cross
      over conditions. The clinical evaluation was performed using CISSD-SDS. Side
      effects were evaluated using the Simpson and Angus Extrapyramidal Side Effects
      Scale (EPSE) and specific check-lists for anticholinergic and endocrine side
      effects. Levosulpiride significantly reduced the number of SD symptoms compared
      to placebo ( P =0.007) after 4 weeks of treatment. Eighty per cent of positive
      responses were observed during treatment with levosulpiride in the placebo
      levosulpiride sequence; on the other hand, only 44% of positive responses were
      found during treatment with active compound in the levosulpiride-placebo sequence
      ( P <0.002). Levosulpiride also determined a more evident reduction of the total
      number of SD symptoms compared to placebo ( P <0.001). There were no differences
      in endocrine and anticholinergic side effects between levosulpiride and placebo.
      In the levosulpiride group, a higher percentage of patients (13.4 vs. 2.8%; P
      =0.029) showed signs of extrapyramidal system involvement compared to placebo.
      Levosulpiride appears to be a well-tolerated and effective drug for the treatment
      for SDs. 

PMID- 24922182
TI  - Quality of Life in 833 outpatients with major depression treated with open-label
      venlafaxine extended release: An observational 24-week study.
AB  - BACKGROUND Quality of Life (QoL) assessments are common in medicine and,
      recently, in psychiatry, mostly in patients with chronic mental illness. We
      evaluated QoL in depressed outpatients treated with venlafaxine-XR over a period
      of 24 weeks. METHOD We evaluated 833 patients with DSM-IV major depression using
      the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale
      (HAM-A), the Montgomery-Asberg Depression Rating Scale (MADRS), and the QoL in
      Depression Scale (QLDS). The patients received venlafaxine-XR and we evaluated
      them after 4, 8, and 24 weeks of treatment. RESULTS HAM-D scores decreased from a
      baseline of 24.6 &#45 6.3 to 6.0 &#45 5.5 (mean &#45 SD; P <0.0001) after 24
      weeks. HAM-A scores decreased from a baseline of 32.3 &#45 7.9 to 6.8 &#45 6.8 (
      P <0.0001) after 24 weeks. QLDS scores decreased from a baseline of 25.8 &#45 5.8
      to 6.6 &#45 7.5 ( P <0.0001) after 24 weeks, indicating improvement in QoL. The
      response after 4 weeks was also significant and continued improving during the
      study. Venlafaxine-XR was shown to be safe and well tolerated. DISCUSSION Open
      label venlafaxine-XR was safe, effective, well tolerated, and improved not only
      depression and anxiety symptoms, but also QoL, in outpatients with major
      depression. This study has the limitations of any non-randomized, non-blinded
      multiple-site clinical trial. 

PMID- 24922183
TI  - Veganism Is a Viable Alternative to Conventional Diet Therapy for Improving Blood
      Lipids and Glycemic Control.
AB  - The American Diabetes Association (ADA) and the National Cholesterol Education
      Program (NCEP) have each outlined a set of dietary recommendations aimed at
      improving glycemic control and blood lipids, respectively. However, traditional
      vegan diets (low-fat diets that proscribe animal product consumption) are also
      effective at improving glycemic control, and dietary portfolios (vegan diets that
      contain prescribed amounts of plant sterols, viscous fibers, soy protein, and
      nuts) are also effective at improving blood lipids. The purpose of this review
      was to compare the effects of traditional vegan diets and dietary portfolios with
      ADA and NCEP diets on body weight, blood lipids, blood pressure, and glycemic
      control. The main findings are that traditional vegan diets appear to improve
      glycemic control better than ADA diets in individuals with type 2 diabetes
      mellitus (T2DM), while dietary portfolios have been consistently shown to improve
      blood lipids better than NCEP diets in hypercholesterolemic individuals. 

PMID- 24922184
TI  - Comparative analysis of bacterial diversity and communities inhabiting the fairy
      ring of Tricholoma matsutake by barcoded pyrosequencing.
AB  - AIMS: Comparative analysis of the soil bacterial communities inhabiting the fairy
      ring of Tricholoma matsutake. METHODS AND RESULTS: The bacterial communities in
      soil samples collected from inside, beneath and outside the T. matsutake fairy
      ring were investigated using barcoded pyrosequencing. A total of 15 129 reads
      were obtained, and 500-536 operational taxonomic units were observed at a 97%
      similarity level. Taxonomic analysis showed similar taxa distribution patterns
      inside and beneath the fairy ring. Three bacterial phyla, Proteobacteria,
      Acidobacteria and Actinobacteria, were dominant in all sampling sites. A heat-map
      analysis of the bacterial genera showed that the uncultured bacterium EU445199
      was remarkably abundant outside the fairy ring, and the uncultured bacteria
      GU727715 and DQ451510 were more and less abundant, respectively, beneath the
      fairy ring than inside and outside the fairy ring. CONCLUSIONS: The results
      indicated that there was no significant difference in bacterial diversity inside,
      beneath and outside the fairy ring even though T. matsutake is predominant
      beneath the fairy ring. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the
      first report on the numerous culturable, unculturable and unclassified bacteria
      in the fairy ring of T. matsutake using the pyrosequencing method.

PMID- 24922185
TI  - The ultrastructure of type I collagen at nanoscale: large or small D-spacing
      distribution?
AB  - D-Spacing is the most significant topographic feature of type I collagen fibril,
      and it is important for our understanding of the structure and function in
      collagens. Traditionally, the D-spacing of type I collagen fibril was shown to
      have a singular value of 67 nm, but recent works indicated that the D-spacing
      values have a large distribution of up to 10 nm when measured by atomic force
      microscopy. We found that this large distribution of D-spacing values mainly
      resulted from image drift during measurement. Note that the D-spacing was
      homogeneous in a single type I collagen fibril. Our statistical analysis
      indicated that the D-spacing values of type I collagen fibrils exhibited only a
      narrow distribution of 2.5 nm around the value of 67 nm. In addition, the D
      spacing values of the collagen fibrils were nearly identical not only within a
      single fibril bundle, but also in different fibril bundles. The measurement of
      the D-spacing values of collagen may provide important structural information in
      many research areas such as collagen related diseases, construction of molecular
      model of collagen, and collagen fibrogenesis. 

PMID- 24922187
TI  - A mystery caller evaluation of emergency contraception supply practices in
      community pharmacies in Victoria, Australia.
AB  - The aim of this study was to determine supply practices of Victorian community
      pharmacies in relation to the emergency contraceptive pill (ECP), following
      release of an updated guideline by the Pharmaceutical Society of Australia.
      Telephone call scripts were developed for three scenarios in which the ECP was
      requested: outside the licensed 72-h time frame (Scenario 1); by a woman under 16
      years (Scenario 2); and for future use (Scenario 3). From 1222 pharmacies, 515
      were randomly selected and allocated into three groups: 177 to Scenario 1 and 169
      to each of Scenarios 2 and 3. Pharmacists' responses were categorised as 'yes',
      'no' or 'ambiguous' and descriptive statistics were calculated. The results are
      as follows. Scenario 1: over half (55.4%; 92/166) declined supply and most
      referred to the doctor, citing the time frame or the ECP as no longer being
      effective reasons. Decreased effectiveness was readily discussed among those
      willing to supply. Scenario 2: more than half (53.9%, 89/165) agreed to supply,
      assessing the request against eligibility criteria outlined in the guideline;
      however, 5.6% (5/89) were only willing if the woman obtained a doctor's
      prescription or recommendation. Scenario 3: less than half (40.5%; 66/163)
      declined supply, mainly due to no therapeutic need. Only four respondents willing
      to give the ECP knew that supply was bona fide. In conclusion, pharmacists'
      practices are variable and not always in line with the recommendations of the
      Pharmaceutical Society of Australia guideline. Pharmacists' awareness of the
      guideline needs to be raised so women can unobtrusively access the ECP.

PMID- 24922186
TI  - Soluble epoxide hydrolase inhibitor attenuates inflammation and airway
      hyperresponsiveness in mice.
AB  - Control of airway inflammation is critical in asthma treatment. Soluble epoxide
      hydrolase (sEH) has recently been demonstrated as a novel therapeutic target for
      treating inflammation, including lung inflammation. We hypothesized that
      pharmacological inhibition of sEH can modulate the inflammatory response in a
      murine ovalbumin (OVA) model of asthma. BALB/c mice were sensitized and exposed
      to OVA over 6 weeks. A sEH inhibitor (sEHI) was administered for 2 weeks.
      Respiratory system compliance, resistance, and forced exhaled nitric oxide were
      measured. Lung lavage cell counts were performed, and selected cytokines and
      chemokines in the lung lavage fluid were measured. A LC/MS/MS method was used to
      measure 87 regulatory lipids mediators in plasma, lung tissue homogenates, and
      lung lavage fluid. The pharmacological inhibition of sEH increased concentrations
      of the antiinflammatory epoxy eicosatrienoic acids and simultaneously decreased
      the concentrations of the proinflammatory dihydroxyeicosatrienoic acids and
      dihydroxyoctadecenoic acids. All monitored inflammatory markers, including FeNO
      levels, and total cell and eosinophil numbers in the lung lavage of OVA-exposed
      mice were reduced by sEHI. The type 2 T helper cell (Th2) cytokines (IL-4, IL-5)
      and chemokines (Eotaxin and RANTES) were dramatically reduced after sEHI
      administration. Resistance and dynamic lung compliance were also improved by
      sEHI. We demonstrated that sEHI administration attenuates allergic airway
      inflammation and airway responsiveness in a murine model. sEHI may have potential
      as a novel therapeutic strategy for allergic asthma. 

PMID- 24922188
TI  - SiPM optical crosstalk amplification due to scintillator crystal: effects on
      timing performance.
AB  - For a given photon detection efficiency (PDE), the primary, Poisson distributed,
      dark count rate of the detector (DCR0) is one of the most limiting factors
      affecting the timing resolution of a silicon photomultiplier (SiPM) in the
      scintillation light readout. If the effects of DCR0 are removed through a
      suitable baseline compensation algorithm or by cooling, it is possible to clearly
      observe another phenomenon that limits the PDE, and thus the timing resolution of
      the detector. It is caused by the optical crosstalk of the SiPM, which is
      significantly increased by the presence of the scintillator. In this paper, we
      describe this phenomenon, which is also easily observed from the reverse I-V
      curve of the device, and we relate it to the measured coincidence resolving time
      in 511 keV gamma-ray measurements. We discuss its consequences on the SiPM design
      and, in particular, we observe that there is an optimal cell size, dependent on
      both SiPM and crystal parameters, that maximizes the PDE in presence of optical
      crosstalk. Finally, we report on a crosstalk simulator developed to study the
      phenomenon and we compare the simulation results obtained for different SiPM
      technologies, featuring different approaches to the reduction of the crosstalk. 

PMID- 24922189
TI  - Sensitive allele-specific real-time PCR test for mutations in BRAF codon V600 in
      skin melanoma.
AB  - Mutations at BRAF codon V600 are used as predictive biomarkers for targeted
      therapy of skin melanoma. Here, a simple sensitive test to detect mutations of
      BRAF-V600 was developed using real-time PCR with allele-specific primers and
      TaqMan probes. Two versions of the test using sense and antisense allele-specific
      primers were designed and evaluated. The test detected 1% mutant allele V600E/K
      in 10 ng DNA standard made from wild-type human DNA spiked with BRAF-V600E or the
      V600K plasmid. The test was validated on clinical formalin-fixed paraffin
      embedded samples of skin melanoma using pyrosequencing as a reference method. In
      the clinical samples, we detected the common mutation V600E, as well as the rare
      mutations V600K, V600E2 (codon GAA), V600E2 K601del, V600D-K601del, and V600R. In
      comparison with pyrosequencing, both versions of the test had 100% specificity
      with sensitivities of 97 and 86% for sense and antisense allele-specific primers,
      respectively. Using the PCR test with sense allele-specific primers, mutations in
      V600 were found in 33 of 51 Russian patients (64.7%) with cutaneous melanoma.
      This closed-tube real-time PCR test can be used as a simple and sensitive assay
      for mutations of BRAF-V600 in cutaneous melanoma. 

PMID- 24922190
TI  - Accuracy of sentinel lymph node dissection for melanoma staging in the presence
      of a collision tumour with a lymphoproliferative disease.
AB  - Sentinel lymph node dissection (SLND) identifies melanoma patients with
      metastatic disease who would benefit from radical lymph node dissection (RLND).
      Rarely, patients with melanoma have an underlying lymphoproliferative disease,
      and melanoma metastases might develop as collision tumours in the sentinel lymph
      node (SLN). The aim of this study was to measure the incidence and examine the
      effect of collision tumours on the accuracy of SLND and on the validity of
      staging in this setting. Between 1998 and 2012, 750 consecutive SLNDs were
      performed in melanoma patients using the triple technique (lymphoscintigraphy,
      gamma probe and blue dye). The validity of SLND in collision tumours was
      analysed. False negativity was reflected by the disease-free survival. The
      literature was reviewed on collision tumours in melanoma. Collision tumours of
      melanoma and chronic lymphocytic leukaemia (CLL) were found in two SLN and in one
      RLND (0.4%). Subsequent RLNDs of SLND-positive cases were negative for melanoma.
      The patient with negative SLND developed relapse after 28 months with an inguinal
      lymph node metastasis of melanoma; RLND showed collision tumours. The literature
      review identified 12 cases of collision tumours. CLL was associated with
      increased melanoma incidence and reduced overall survival. This is, to our
      knowledge, the first assessment of the clinical value of SLND when collision
      tumours of melanoma and CLL are found. In this small series of three patients
      with both malignancies present in the same lymph node basin, lymphocytic
      infiltration of the CLL did not alter radioisotope uptake into the SLN. No false
      negative result was observed. Our data suggest the validity of SLND in collision
      tumours, but given the rarity of the problem, further studies are necessary to
      confirm this reliability. 

PMID- 24922191
TI  - Acneiform eruption in a patient with metastatic melanoma after ceasing
      combination dabrafenib/trametinib therapy.
AB  - BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) increase survival in BRAF
      mutant metastatic melanoma patients; however, they induce a well-known spectrum
      of cutaneous side effects during treatment. Whereas the BRAFi dabrafenib induces
      cutaneous squamous cell carcinomas and verrucal keratosis, the MEKi trametinib
      frequently induces acneiform eruptions that are reversible after drug
      discontinuation. Furthermore, when dabrafenib and trametinib are used in
      combination, there are fewer cutaneous toxicities. We report a patient with BRAF
      mutant metastatic melanoma treated with the BRAFi/MEKi combination therapy who
      developed an acneiform eruption after treatment discontinuation rather than
      during active therapy. Moreover, the eruption resolved when the combination
      treatment was reintroduced and recurred after increasing the dose of trametinib.
      The eruption may be explained by the longer half-life of trametinib (4.5 days)
      compared with dabrafenib (5.2 h). This is the first case reported with this
      particular side effect induced after stopping the treatment and could become more
      frequent as the BRAFi/MEKi combination of drugs is more frequently prescribed.

PMID- 24922192
TI  - Aid effectiveness in rebuilding the Afghan health system: a reflection.
AB  - The Paris Declaration defined five components of aid effectiveness: ownership,
      alignment, harmonisation, managing for results and mutual accountability.
      Afghanistan, which has received a high level of donor aid for health since 2002,
      has seen significant improvements in health indicators, expanded access to health
      services and an increased range of services. Do the impressive health outcomes in
      this fragile state mean that aid has been effectively utilised? The factors that
      contributed to the success of the Ministry of Public Health (MOPH)-donor
      partnership include as follows: Ownership: a realistic role for the MOPH as the
      steward of the health sector that was clearly articulated to all stakeholders;
      Donor alignment: donor coordination and collaboration initiated by the MOPH;
      Joint decisions: participatory decision-making by the MOPH and donors, such as
      the major decision to use contracts with nongovernmental organisations for health
      service delivery; Managing for results: basing programmes on available evidence,
      supplementing that evidence where possible and performance monitoring of health
      sector activities using multiple data sources; Reliable aid flows: the
      availability of sufficient donor funding for more than 10 years for MOPH
      priorities, such as the Basic Package of Health Services, and other programmes
      that boosted system development and capacity building; Human factors: these
      include a critical mass of individuals with the right experience and expertise
      being deployed at the right time and able to look beyond agency mandates and
      priorities to support sector reform and results. These factors, which made aid to
      Afghanistan effective, can be applied in other countries. 

PMID- 24922193
TI  - Fluorescence adaptive optics scanning laser ophthalmoscope for detection of
      reduced cones and hypoautofluorescent spots in fundus albipunctatus.
AB  - IMPORTANCE: Fundus albipunctatus (FA) is a form of congenital stationary night
      blindness characterized by yellow-white spots, which were classically described
      as subretinal. Although night blindness and delayed dark adaptation are hallmarks
      of this condition, recent studies have described a macular phenotype,
      particularly among older patients. Using a fluorescence adaptive optics scanning
      laser ophthalmoscope (FAOSLO), this study provides in vivo morphologic data at
      the cellular level in FA. OBJECTIVE: To study the cone photoreceptors and the
      albipunctate spots in FA at single-cell resolution. DESIGN, SETTING, AND
      PARTICIPANT: A woman in her 30s with FA underwent a complete ophthalmic
      examination, including conventional imaging tests, at the University of
      Rochester. A FAOSLO was used to obtain infrared reflectance images of the cone
      mosaic at the central fovea and along the superior and temporal meridians to 10
      degrees  eccentricity. Cone density was measured at the foveal center, and cone
      spacing was calculated in sampling windows eccentrically. In the area of the
      albipunctate spots, autofluorescence FAOSLO images (excitation, 561 nm; emission,
      624 Delta 40 nm) were simultaneously obtained. MAIN OUTCOMES AND MEASURES:
      Structural appearance of cones, cone density and spacing, and reflectance and
      autofluorescence of albipunctate spots. RESULTS: Cone density was reduced to 70%
      of the lower limit of the normal range at the foveal center (78.7 * 10(3)
      cones/mm(2); mean [SD] reference range, 199 [87] * 10(3) cones/mm(2)), and cone
      spacing was increased eccentrically to 10 degrees  (sign test, P = .045).
      Individual cone central core reflectances appeared dim, suggesting loss of
      photoreceptor outer segments. The albipunctate spots were hypoautofluorescent. No
      photoreceptors or retinal pigment epithelium cells were identified at the
      locations of the albipunctate spots. CONCLUSIONS AND RELEVANCE: Although the
      predominant clinical symptom of night blindness and the electroretinography
      results suggest a primary rod dysfunction, examination with a FAOSLO demonstrates
      that cone density is also reduced. This finding may represent an early sign of
      progression to macular phenotype in FA. The hypoautofluorescence suggests that
      the albipunctate spots do not represent lipofuscin.

PMID- 24922195
TI  - Elevated serum levels of calprotectin (myeloid-related protein 8/14) in patients
      with ankylosing spondylitis and its association with disease activity and quality
      of life.
AB  - BACKGROUND: Calprotectin is one of the major leukocyte S100 proteins showing both
      calcium binding and antimicrobial characteristics. The serum level of
      calprotectin is markedly elevated in patients with inflammatory bowel disease,
      rheumatoid arthritis, as well as systemic lupus erythematosus and has been
      suggested to play a prominent role in both progression and pathogenesis of these
      diseases. AIM: The purpose of this study was to investigate the serum level of
      calprotectin in patients with ankylosing spondylitis (AS) and its association
      with disease activity and other clinical characteristics of AS. MATERIALS AND
      METHODS: Thirty-one patients who met the modified New York criteria for AS and 45
      healthy controls were included in this study. Both Bath AS disease activity index
      and AS disease activity score were applied on the patients with AS for the
      assessment of disease activity; Bath AS functional index, for the assessment of
      functional activity; Bath AS radiology index, for the assessment of radiological
      damage; and the AS quality of life questionnaire for the assessment of disease
      related life status. Spinal and hip measurements were performed using Bath AS
      metrology index. The serum level of calprotectin was determined using enzyme
      linked immunosorbent assay kit. RESULTS: Mean serum level of calprotectin was
      significantly higher in the patients with AS compared with healthy controls (P =
      0.003). Serum levels of calprotectin did not correlate with Bath AS disease
      activity index, AS disease activity score, Bath AS functional index, Bath AS
      radiology index, Bath AS metrology index, modified Schober, chest expansion, AS
      quality of life questionnaire, erythrocyte sedimentation rate, and C-reactive
      protein values (P > 0.05). CONCLUSIONS: Our results suggest that calprotectin
      might play an important role in the pathogenetic mechanisms of AS; however, the
      calprotectin levels did not correlate with the measurements of disease activity,
      functional abilities, radiological damage, and the quality of life in these
      patients. Further insight into this area of research might provide opportunities
      to develop novel treatment strategies, which take into account the role of these
      peptides in the pathogenetic mechanisms of AS.

PMID- 24922196
TI  - Prolonged QT interval in ST-elevation myocardial infarction and mortality: new
      prognostic scale with QT, Killip and age.
AB  - AIMS: To analyze the relation between prolonged QT interval and mortality in
      patients with ST-elevation myocardial infarction and complementarity with Killip,
      Thrombolysis in Myocardial Infarction (TIMI) and Acute Physiology and Chronic
      Health Evaluation-II (APACHE-II) scales. METHODS: A nested cohort case-control
      study was conducted in a Spanish hospital. The cohort consisted of patients with
      ST-elevation myocardial infarction admitted between 2008 and 2010 (n = 524). The
      cases were the patients who died (n = 38) and the controls (n = 81) were a random
      sample of those who survived (one of every six). RESULTS: The corrected QT (QTc)
      interval of first ECG (prehospital-or-hospital admission) was prolonged in 18 of
      the 35 patients who died (51.4%) and in 12 of the controls (16.7%; P < 0.001).
      APACHE-II, TIMI and Killip scores were higher in the patients who had died (P <
      0.001). Mortality with prolonged QTc (19.3%) was 20%, and 4.5% were with normal
      QTc (80.7%; P < 0.001).Logistic regression showed a relation between mortality
      with prolonged QTc and TIMI [odds ratio (OR) 3.57(1.16-10.97)]. A second model
      was constructed with APACHE-II and prolonged QTc [OR 6.47(1.77-23.59)]; receiver
      operating characteristic (ROC) curve area [0.92(0.87-0.97)], and individually,
      for APACHE-II was 0.88 (0.81-0.95). A new score was constructed: QTc (not
      prolonged: 0 points, prolonged: 7 points), age (<65 years: 0 points, 65-74 years:
      6 points, >=75 years: 9 points), Killip (I: 0 points, II-III: 4 points, IV: 17
      points). ROC area: 0.88. CONCLUSIONS: Hospital mortality was higher with
      prolonged QTc at prehospital-or-hospital admission, given equal Killip, TIMI and
      APACHE values. Discrimination of Killip, TIMI and APACHE values can be improved
      with prolonged QTc. Discrimination of a model including Killip, age and prolonged
      QTc is quite good. We have made a new simple prognostic scale with these
      variables.

PMID- 24922194
TI  - Two splicing factors carrying serine-arginine motifs, TSR1 and TSR1IP, regulate
      splicing, mRNA stability, and rRNA processing in Trypanosoma brucei.
AB  - In trypanosomes, mRNAs are processed by trans-splicing; in this process, a common
      exon, the spliced leader, is added to all mRNAs from a small RNA donor, the
      spliced leader RNA (SL RNA). However, little is known regarding how this process
      is regulated. In this study we investigated the function of two serine-arginine
      rich proteins, TSR1 and TSR1IP, implicated in trans-splicing in Trypanosoma
      brucei. Depletion of these factors by RNAi suggested their role in both cis- and
      trans-splicing. Microarray was used to examine the transcriptome of the silenced
      cells. The level of hundreds of mRNAs was changed, suggesting that these proteins
      have a role in regulating only a subset of T. brucei mRNAs. Mass-spectrometry
      analyses of complexes associated with these proteins suggest that these factors
      function in mRNA stability, translation, and rRNA processing. We further
      demonstrate changes in the stability of mRNA as a result of depletion of the two
      TSR proteins. In addition, rRNA defects were observed under the depletion of
      U2AF35, TSR1, and TSR1IP, but not SF1, suggesting involvement of SR proteins in
      rRNA processing. 

PMID- 24922197
TI  - Variations of electroanatomic substrates and markers of successful ablation in
      idiopathic left ventricular tachycardia: role of electroanatomic substrates and
      potential mechanism of tachycardia.
AB  - OBJECTIVES: The variation of the substrates of verapamil-sensitive idiopathic
      left ventricular tachycardia (ILVT) was not understood. The purpose of this study
      was to investigate the variation of electroanatomic substrate [slow conduction
      zone (SCZ) and left ventricular conduction system (LVCS)] in ILVT and control
      individuals and markers of successful ablation. METHODS: Electroanatomical
      mapping was performed during sinus rhythm in 20 ILVT patients and 26 control
      individuals with paroxysmal supraventricular tachycardia. LVCS and SCZ were
      tagged in geometry and the anatomic aspects were investigated. RESULTS: According
      to the distribution of Purkinje potential, LVCS was distinguished into three
      types: left bundle branch (LBB) was divided into two discrete fascicles without
      interconnections; divided into three separate fascicles; and fanlike structure
      distribution over septum broadly. The length of LBB and its fascicles in patients
      with ILVT were slightly longer than those of controls (P > 0.05). In the ILVT
      group, the SCZ was located at the inferoposterior septum in 17, inferior apical
      septum in one and two SCZs were located at the posterior and mid-septal in the
      other two patients, which were greater in size and longer in length than those of
      six controls (P < 0.05). At the crossover junction area with diastolic potential
      and Purkinje potential, with the size of 1.5 +/- 0.4 cm(2), concealed
      entertainment and ablation were obtained successfully in all patients with ILVT.
      CONCLUSION: The anatomy of the LVCS and SCZ is highly variable in patients with
      ILVT, and the crossover junction area with diastolic potential and Purkinje
      potential might be a marker of ablation.

PMID- 24922198
TI  - Ivabradine treatment prevents dobutamine-induced increase in heart rate in
      patients with acute decompensated heart failure.
AB  - BACKGROUND: Ivabradine is a heart rate (HR)-lowering agent acting by inhibiting
      the If-channel. Dobutamine does increase the HR and has some deleterious effects
      on myocardium. So, we aimed to evaluate whether ivabradine treatment blunts a
      dobutamine-induced increase in HR. METHODS: The main study population consisted
      of 58 acute decompensated heart failure patients requiring inotropic support with
      left-ventricular ejection fraction below 35%, who were randomized to ivabradine
      (n = 29) or control (n = 29). All patients underwent Holter recording for 6 h and
      then dobutamine was administered at incremental doses of 5, 10 and 15 MUg/kg/min,
      with 6-h steps. Holter recording was continued during dobutamine infusion.
      Ivabradine 7.5 mg was given at the initiation of dobutamine and readministered at
      12 h of infusion. Also, a nonrandomized beta-blocker group with 15 patients
      receiving beta-blocker was included in the analysis. Control and beta-blocker
      groups did not receive ivabradine. RESULTS: In the control group, mean HR
      gradually and significantly increased at each step of dobutamine infusion (81 +/-
      11, 90 +/- 16, 97 +/- 14 and 101 +/- 16 b.p.m., respectively; P = 0.001), whereas
      no significant increase in HR was observed in the ivabradine group (82 +/- 17, 82
      +/- 15, 85 +/- 14 and 83 +/- 12 b.p.m., respectively; P = 0.439). Mean HR was
      also found to significantly increase during dobutamine infusion in the beta
      blocker group (75 +/- 13, 82 +/- 13, 86 +/- 14 and 88 +/- 13 b.p.m.,
      respectively; P = 0.001). The median increase in HR from baseline was
      significantly higher in the control group compared to those in the ivabradine
      group (5 vs. 2 b.p.m.; P = 0.007 at first step, 13 vs. 5 b.p.m.; P = 0.001 at
      second step and 18 vs. 6 b.p.m.; P = 0.0001 at third step of dobutamine,
      respectively). CONCLUSIONS: Ivabradine treatment prevents dobutamine-induced
      increase in HR and may be useful in reducing HR-related adverse effects of
      dobutamine.

PMID- 24922200
TI  - Dimensionless parameterization of lidar for laser remote sensing of the
      atmosphere and its application to systems with SiPM and PMT detectors.
AB  - In this paper, we show a renewed approach to the generalized methodology for
      atmospheric lidar assessment, which uses the dimensionless parameterization as a
      core component. It is based on a series of our previous works where the problem
      of universal parameterization over many lidar technologies were described and
      analyzed from different points of view. The modernized dimensionless
      parameterization concept applied to relatively new silicon photomultiplier
      detectors (SiPMs) and traditional photomultiplier (PMT) detectors for remote
      sensing instruments allowed predicting the lidar receiver performance with sky
      background available. The renewed approach can be widely used to evaluate a broad
      range of lidar system capabilities for a variety of lidar remote-sensing
      applications as well as to serve as a basis for selection of appropriate lidar
      system parameters for a specific application. Such a modernized methodology
      provides a generalized, uniform, and objective approach for evaluation of a broad
      range of lidar types and systems (aerosol, Raman, DIAL) operating on different
      targets (backscatter or topographic) and under intense sky background conditions.
      It can be used within the lidar community to compare different lidar instruments.

PMID- 24922201
TI  - Integral image rendering procedure for aberration correction and size
      measurement.
AB  - The challenge in rendering integral images is to use as much information
      preserved by the light field as possible to reconstruct a captured scene in a
      three-dimensional way. We propose a rendering algorithm based on the projection
      of rays through a detailed simulation of the optical path, considering all the
      physical properties and locations of the optical elements. The rendered images
      contain information about the correct size of imaged objects without the need to
      calibrate the imaging device. Additionally, aberrations of the optical system may
      be corrected, depending on the setup of the integral imaging device. We show
      simulation data that illustrates the aberration correction ability and
      experimental data from our plenoptic camera, which illustrates the capability of
      our proposed algorithm to measure size and distance. We believe this rendering
      procedure will be useful in the future for three-dimensional ophthalmic imaging
      of the human retina. 

PMID- 24922202
TI  - Advanced birefringence measurements in standard terahertz time-domain
      spectroscopy.
AB  - Polarization-sensitive (PS) terahertz (THz) technology can be used for
      investigating anisotropic materials that are opaque for visible light. A full
      characterization of an anisotropic material requires the extraction of the
      birefringence as well as the orientation of the optical axis from the measurement
      data. We present an approach based on THz time-domain spectroscopy (TDS) that
      exploits the spectral content of the THz signal for determining these two
      parameters from only two measurements. In contrast to an earlier approach with a
      more sophisticated PS-THz system and quasi-circularly polarized THz radiation,
      now a simple standard THz-TDS system can be employed. After a description of the
      mathematical model for data analysis we demonstrate the applicability of our
      method for a lithium niobate crystal and furthermore for a glass-fiber reinforced
      polymer sample, for which the orientation of the optical axis and birefringence
      are obtained in a spatially resolved way, showing the potential of the method
      also for PS-THz imaging. As no specialized setup or components are required, our
      approach can be easily and extensively applied for the analysis of anisotropic
      samples at THz frequencies. 

PMID- 24922203
TI  - Ytterbium-doped large-mode-area silica fiber fabricated by using chelate
      precursor doping technique.
AB  - We reported on a highly effective chelate precursor doping technique for Yb-doped
      large-mode-area (LMA) fiber manufacture. By accurately controlling the
      evaporation temperature and flow rate of carrier gas, the chelate precursor
      doping technique is capable of making Yb-doped LMA silica fiber with good
      uniformity free of center dip, low numerical aperture of ~0.056, large preform
      core size of 4.46 mm, and appropriate cladding absorption of 1.17  dB/m at 976.4
      nm. Based on a single-end-pump all-fiber oscillator laser setup, the laser output
      at 1080 nm reached 700 W with slope efficiency of 54.2%.

PMID- 24922204
TI  - Investigation of the Young's modulus and thermal expansion of amorphous titania
      doped tantala films.
AB  - The current generation of advanced gravitational wave detectors utilize titania
      doped tantala/silica multilayer stacks for their mirror coatings. The properties
      of the low-refractive-index silica are well known; however, in the absence of
      detailed direct measurements, the material parameters of Young's modulus and
      coefficient of thermal expansion (CTE) of the high refractive index material,
      titania-doped tantala, have been assumed to be equal to values measured for pure
      tantala coatings. In order to ascertain the true values necessary for thermal
      noise calculations, we have undertaken measurements of Young's modulus and CTE
      through the use of nanoindentation and thermal-bending measurements. The
      measurements were designed to assess the effects of titania-doping concentration
      and post-deposition heat-treatment on the measured values in order to evaluate
      the possibility of optimizing material parameters to further improve thermal
      noise in the detector. Young's modulus measurements on pure tantala and 25% and
      55% titania-doped tantala show a wide range of values, from 132 to 177 GPa, which
      are dependent on both titania concentration and heat-treatment. Measurements of
      CTE give values of (3.9+/-0.1)*10-6 K-1 and (4.9+/-0.3)*10-6 K-1 for 25% and 55%
      titania-doped tantala, respectively, without dependence on post-deposition heat
      treatment.

PMID- 24922205
TI  - Comparative analysis on viewing angle change in Fresnel and Fourier holographic
      images reconstructed by a tilted plane wave.
AB  - We carry out a comparative analysis on a viewing angle change in Fresnel and
      Fourier holographic images reconstructed by a tilted plane wave. A tilted plane
      wave illuminating an on-axis hologram generates a diffractive wave carrying the
      holographic image in a paraxial region of a new diffraction axis. The
      reconstructed image in the Fresnel hologram is deformed along the new viewing
      direction, which is well described as Affine transformation. In the Fourier
      holographic image, the replica of the image is formed without its deformation
      when the hologram is placed in the front focal plane of the lens, whereas in the
      case of a hologram that is located at a distance different from a focal length,
      image deformation arises. This property is investigated through numerical
      simulation based on a wide-angle diffraction phenomenon. We also perform a
      similar interpretation for high-order diffraction images appearing in the sampled
      Fourier hologram and discuss a method for enlarging the viewing angle of the
      holographic image. 

PMID- 24922206
TI  - Modified dwell time optimization model and its applications in subaperture
      polishing.
AB  - The optimization of dwell time is an important procedure in deterministic
      subaperture polishing. We present a modified optimization model of dwell time by
      iterative and numerical method, assisted by extended surface forms and tool paths
      for suppressing the edge effect. Compared with discrete convolution and linear
      equation models, the proposed model has essential compatibility with arbitrary
      tool paths, multiple tool influence functions (TIFs) in one optimization, and
      asymmetric TIFs. The emulational fabrication of a Phi200  mm workpiece by the
      proposed model yields a smooth, continuous, and non-negative dwell time map with
      a root-mean-square (RMS) convergence rate of 99.6%, and the optimization costs
      much less time. By the proposed model, influences of TIF size and path interval
      to convergence rate and polishing time are optimized, respectively, for typical
      low and middle spatial-frequency errors. Results show that (1) the TIF size is
      nonlinear inversely proportional to convergence rate and polishing time. A TIF
      size of ~1/7 workpiece size is preferred; (2) the polishing time is less
      sensitive to path interval, but increasing the interval markedly reduces the
      convergence rate. A path interval of ~1/8-1/10 of the TIF size is deemed to be
      appropriate. The proposed model is deployed on a JR-1800 and MRF-180 machine.
      Figuring results of Phi920  mm Zerodur paraboloid and Phi100  mm Zerodur plane by
      them yield RMS of 0.016lambda and 0.013lambda (lambda=632.8  nm), respectively,
      and thereby validate the feasibility of proposed dwell time model used for
      subaperture polishing.

PMID- 24922207
TI  - Design of an omnidirectional optical antenna for ultraviolet communication.
AB  - In this paper we propose an omnidirectional large field-optical antenna with a
      dual-mirror structure and field devices and demonstrate its utilization in
      ultraviolet (UV) communications. Theoretical analysis shows that it is suitable
      for short-range UV communication. Simulation indicates that the optical gain is
      32, and the system has a good spot uniformity. Additionally, incident angles of
      incident ray meet the requirement of the interference filter (+/-10 degrees ).
      Outdoor experiments show that the angle of FOV is in the range of +/-20 degrees
      ~+/-80 degrees  and a SNR increase of 31 dB compared with bare tube is observed,
      demonstrating the effectiveness of the omnidirectional optical antenna structure
      for free-space UV communication.

PMID- 24922208
TI  - Partially coherent digital in-line holographic microscopy in characterization of
      a microscopic target.
AB  - Digital holographic microscopy enables the capture of large three-dimensional
      volumes. Instead of using a laser as an illumination source, partially coherent
      alternatives can be used, such as light-emitting diodes, which produce parasitic
      reflection and speckle-free holograms. Captured high-contrast holograms are
      suitable for the characterization of micrometer-sized particles. As the
      reconstructed phase is not usable in the case of multiple overlapping objects,
      depth extraction can be conducted on a reconstructed intensity. This work
      introduces a novel depth extraction algorithm that takes into consideration the
      possible locations of multiple objects at various depths in the imaged volume.
      The focus metric, the Tamura coefficient, is applied for each pixel in the
      reconstructed amplitude throughout the volume. This work also introduces an
      optimized version of the algorithm, which is run in two stages. During the first
      stage, coarse positions of the objects are extracted by applying the Tamura
      coefficient to nonoverlapping window blocks of intensity reconstructions. The
      second stage produces high-precision characterizations of the objects by
      calculating the Tamura coefficient with overlapping window blocks around axial
      positions extracted in the first stage. Experimental results with real-world
      microscopic objects show the effectiveness of the proposed method. 

PMID- 24922209
TI  - Theoretical modeling of lossy mode resonance based refractive index sensors with
      ITO/TiO2 bilayers.
AB  - A lossy mode resonance (LMR) based fiber optic refractive index (RI) sensor
      utilizing indium tin oxide (ITO)/titanium dioxide (TiO2) bilayers has been
      theoretically investigated. Specifically, the effect of different thickness
      ratios of bilayers on the sensitivity to surrounding medium RI variations was
      studied. It was observed that for a specific thickness ratio, a two fold increase
      in sensitivity can be achieved in comparison to conventional LMR sensors using a
      single absorbing thin film. The sensitivity can be enhanced by tuning the total
      bilayer thickness and bilayer thickness ratio for the desired application, which
      is not possible in conventional LMR sensors.

PMID- 24922210
TI  - Analytic study of traveling-wave velocity variation in line-focusing schemes for
      plasma x-ray lasers.
AB  - Efficient amplification of coherent short-wavelength pulses along a plasma gain
      column requires traveling-wave excitation with the sweep velocity matched to the
      signal group velocity. Through simulations incorporating the gain dynamics of the
      system, we show that the group velocity is not constant but increases
      monotonically along the line focus due to strong saturation. We demonstrate a
      line-focusing configuration that results in traveling wave excitation with the
      sweep velocity well matched to the spatially varying group velocity. Moreover, we
      show through numerical simulations that the improved velocity matching yields a
      significant improvement in signal amplification. 

PMID- 24922211
TI  - Design and optimization of an adaptive optics system for a high-average-power
      multi-slab laser (HiLASE).
AB  - We report numerical and experimental results obtained with an optical setup that
      simulates the heating and cooling processes expected in a multi-slab high-average
      power laser head. We have tested the performance of an adaptive optics system
      consisting of a photo-controlled deformable mirror (PCDM) and a Shack-Hartmann
      wavefront sensor for the effective correction of the generated wavefront
      aberrations. The performance of the adaptive optics system is characterized for
      different layouts of the actuator array and for different configurations of the
      heating mechanisms. The numerical results are benchmarked using a PCDM, which
      allowed us to experimentally compare the performances of different deformable
      mirrors. 

PMID- 24922212
TI  - Frequency doubling of a passively mode-locked monolithic distributed Bragg
      reflector diode laser.
AB  - In this work, frequency doubling of a passively mode-locked 3.5 mm long
      monolithic distributed Bragg reflector diode laser is investigated
      experimentally. At 1064 nm, optical pulses with a duration of 12.4 ps are
      generated at a repetition rate of 13 GHz and a peak power of 825 mW, resulting in
      an average power of 133 mW. Second-harmonic generation is carried out in a
      periodically poled MgO-doped LiNbO3 ridge waveguide at a normalized nonlinear
      conversion efficiency of 930%/W. A maximum average second-harmonic power of 40.9
      mW, corresponding to a pulse energy of 3.15 pJ, is reached in the experiment at
      an opto-optical conversion efficiency of 30.8%. The normalized nonlinear
      conversion efficiency in mode-locked operation is more than 2 times larger
      compared to continuous-wave operation.

PMID- 24922213
TI  - Coherent characteristics of solid-state lasers with corner cubes.
AB  - A corner cube (CC) as a peculiar coherent combination element is first, to the
      best of our knowledge, theoretically and experimentally proved by the authors.
      When a CC is used as a total-reflecting mirror in the solid-state laser resonator
      it can improve the laser far-field energy focalization. Furthermore, the
      differences between the coherent characteristics of the lasers with a corner cube
      resonator (CCR) and those with a Fabry-Perot resonator have been investigated,
      respectively. Theoretical calculation and numerical simulation have proved that
      the symmetric output beams of the CCR laser are coherent and the adjacent output
      beams are partially coherent. Based on these special coherent characteristics, a
      new laser coherent combining configuration, in which a CC was utilized as a total
      reflecting mirror, was proposed and experimentally investigated. In our
      experiments, the measured far-field intensity profiles of coherent combing laser
      arrays are in good agreement with the numerical simulation. These novel coherent
      characteristics of a CC may be important for applications in solid-state lasers
      and laser coherent combining systems, and coherent combination may be one of the
      development trends and future research directions for CCR lasers. 

PMID- 24922214
TI  - Silver nanowire composite thin films as transparent electrodes for
      Cu(In,Ga)Se2/ZnS thin film solar cells.
AB  - Solution processed silver nanowire indium-tin oxide nanoparticle (AgNW-ITONP)
      composite thin films were successfully applied as the transparent electrodes for
      Cu(In,Ga)Se2 (CIGS) thin film solar cells with ZnS buffer layers. Properties of
      the AgNW-ITONP thin film and its effects on performance of CIGS/ZnS thin film
      solar cells were studied. Compared with the traditional sputtered ITO electrodes,
      the AgNW-ITONP thin films show comparable optical transmittance and electrical
      conductivity. Furthermore, the AgNW-ITONP thin film causes no physical damage to
      the adjacent surface layer and does not need high temperature annealing, which
      makes it very suitable to use as transparent conductive layers for heat or
      sputtering damage-sensitive optoelectronic devices. By using AgNW-ITONP
      electrodes, the required thickness of the ZnS buffer layers for CIGS thin film
      solar cells was greatly decreased.

PMID- 24922215
TI  - Fiber-optic ground settlement sensor based on low-coherent interferometry.
AB  - Ground settlement (GS) monitoring is a basic prerequisite in civil engineering. A
      commercialized instrument to meet this requirement has been available with
      millimeter accuracy. Major difficulties to improve this to micrometer scale,
      which are needed in special cases such as in high-speed railways, are challenged
      by the long stability of the sensor in the condition of the extremely slow
      settlement. A fiber-optic GS methodology was proposed by using a scanning low
      coherent Michelson interferometer. One of the paths of the interferometer is
      formed by the liquid surface, and therefore the readout of the interferometer can
      make the measurement of the surface approach a micrometer scale. The liquid
      contained chambers are hydraulically connected together at the bottom by using a
      water-filled tube. The liquid surface inside each chamber is at the same level
      initially. One of the chambers is located on stable ground or at a point that can
      be easily surveyed, too. The others are located at the points where settlement or
      heave is to be measured. Differential settlement, or heave, between the chambers
      will result in an apparent rise or fall of the liquid level, which biased the
      initial equal status. The experimental results demonstrated that the best
      accuracy of +/-20  MUm for GS monitoring was obtained with a reference
      compensation sensor.

PMID- 24922216
TI  - Laser frequency stability transfer using a fiber-based interferometer.
AB  - We have demonstrated a method for laser frequency stability transfer using a
      fiber-based Young's interferometer. An 858 nm external cavity diode laser is
      stabilized to within 1e-8 from 10 s to 4000 s, referenced to a Rubidium
      stabilized 780 nm DBR diode laser using the interferometer as a frequency
      stability-transferring link. The system is simple to build and can link any two
      laser wavelengths within the fiber operating range.

PMID- 24922217
TI  - Mean intensity of vortex Bessel beams propagating in turbulent atmosphere.
AB  - Transformation of vortex Bessel beams during propagation in turbulent atmosphere
      is theoretically analyzed. Deforming influence of the random inhomogeneity of the
      turbulent medium on propagation of diffraction-free beams leads to disappearance
      of their invariant properties. In the given research, features of evolution of
      the spatial structure of distribution of mean intensity of vortex Bessel beams in
      turbulent atmosphere are analyzed. A quantitative criterion of possibility of
      carrying over of a dark central domain by vortex Bessel beams in a turbulent
      atmosphere is derived. The analysis of the behavior of several physical
      parameters of mean-level optical radiation shows that the shape stability of a
      vortex Bessel beam increases with the topological charge of this beam during its
      propagation in a turbulent atmosphere. 

PMID- 24922218
TI  - Simulating the dispersive behavior of semiconductors using the Lorentzian-Drude
      model for photovoltaic devices.
AB  - Unique light-trapping structures that improve the efficiency of thin-film solar
      cells require advanced computational methods that can simulate the propagation of
      light through the thickness of each material in the solar cell. The simulations
      community that uses the Lorentz-Drude (LD) model cannot precisely simulate the
      propagation of light through the entire spectrum of the Sun, due to the
      difficulty in extrapolating the coefficients of each solar cell material. In this
      paper, a new technique for modeling dispersive and absorptive material over the
      Sun's entire wavelength range (200-1700 nm) using the LD model is suggested. The
      new numerical models are used for simulating light propagation through various
      one-dimensional light-trapping structures, including metal backreflectors and
      distributed Bragg reflectors. All the numerical simulation results show agreement
      with previously published theoretical and experimental results. The proposed
      simulation technique will help the simulations community in using the LD model to
      simulate the propagation of light in solar cells more accurately.

PMID- 24922219
TI  - Spectral interdependence of remote-sensing reflectance and its implications on
      the design of ocean color satellite sensors.
AB  - Using 901 remote-sensing reflectance spectra (R(rs)(lambda), sr-1, lambda from
      400 to 700 nm with a 5 nm resolution), we evaluated the correlations of
      R(rs)(lambda) between neighboring spectral bands in order to characterize (1) the
      spectral interdependence of R(rs)(lambda) at different bands and (2) to what
      extent hyperspectral R(rs)(lambda) can be reconstructed from multiband
      measurements. The 901 R(rs) spectra were measured over a wide variety of aquatic
      environments in which water color varied from oceanic blue to coastal green or
      brown, with chlorophyll-a concentrations ranging from ~0.02 to >100  mg  m-3,
      bottom depths from ~1  m to >1000  m, and bottom substrates including sand, coral
      reef, and seagrass. The correlation coefficient of R(rs)(lambda) between
      neighboring bands at center wavelengths lambda(k) and lambda(l),
      r(Deltalambda)(lambda(k), lambda(l)), was evaluated systematically, with the
      spectral gap (Deltalambda=lambda(l)-lambda(k)) changing between 5, 10, 15, 20,
      25, and 30 nm, respectively. It was found that r(Deltalambda) decreased with
      increasing Deltalambda, but remained >0.97 for Deltalambda<=20  nm for all
      spectral bands. Further, using 15 spectral bands between 400 and 710 nm, we
      reconstructed, via multivariant linear regression, hyperspectral R(rs)(lambda)
      (from 400 to 700 nm with a 5 nm resolution). The percentage difference between
      measured and reconstructed R(rs) for each band in the 400-700 nm range was
      generally less than 1%, with a correlation coefficient close to 1.0. The mean
      absolute error between measured and reconstructed R(rs) was about 0.00002  sr-1
      for each band, which is significantly smaller than the R(rs) uncertainties from
      all past and current ocean color satellite radiometric products. These results
      echo findings of earlier studies that R(rs) measurements at ~15 spectral bands in
      the visible domain can provide nearly identical spectral information as with
      hyperspectral (contiguous bands at 5 nm spectral resolution) measurements. Such
      results provide insights for data storage and handling of large volume
      hyperspectral data as well as for the design of future ocean color satellite
      sensors.

PMID- 24922220
TI  - Design of resonant cavity structure for efficient high-temperature operation of
      single-photon avalanche photodiodes.
AB  - A novel design of a single-photon avalanche photodiode (SPAD) is proposed based
      on resonant cavity (RC) structure, and its performance is studied. In the
      proposed structure, InAlAs/InGaAs distributed Bragg reflectors (DBRs) are
      employed as top and bottom mirrors and the quantum efficiency (QE) of the
      absorption region is calculated considering the effect of the RC. Results show
      that using 12 periods of DBRs as a bottom reflector without incorporation of a
      top mirror can enhance the QE to about 90% at room temperature. For this RC
      enhanced SPAD, a single-photon quantum efficiency (SPQE) is obtained of about
      0.35 at T=300  K. For temperatures lower than T=260  K, SPQE is about 1. Results
      show that although the RC doesn't affect the dark current, for a given SPQE the
      dark count rate is lower for the RC-SPAD.

PMID- 24922221
TI  - Variation of spectral properties of dielectric ionic crystal in the terahertz
      range due to the polariton absorption.
AB  - The dispersion equations for polariton waves in dielectric ionic crystal with the
      absorption are obtained. The self-consistent solutions of the system of Maxwell
      electromagnetic field equations and the equations of motion of ions have been
      used. The elastic and absorption properties of the crystal are taken into account
      in the ion equations of motion. It is shown that the separated equations of
      motion for positive and negative ions allow obtaining all branches of phonon and
      polariton spectrum by the example of the ionic crystal of cubic symmetry at the
      terahertz range. It has been shown that the variation of absorption in the
      crystal leads to changing of the character of spectrum branch and the polariton
      velocities. 

PMID- 24922222
TI  - SPM and XPM nonlinear effects in plasmonic directional couplers, considering the
      ponderomotive metal nonlinearity.
AB  - In this paper, a two-dimensional nonlinear plasmonic directional coupler (2D
      NPDC), with 90 degrees  waveguide bends, has been numerically analyzed by the
      finite-difference time-domain (FDTD) method, considering the nonlinear response
      of metal due to the ponderomotive force. It has been shown that the required
      switching power of the 2D-NPDC is 0.05% of that when only the dielectric is
      nonlinear and the nonlinearity of metal is neglected. Also, the cross-phase
      modulation (XPM) nonlinear effect has been investigated, which the power for
      switching is decreased significantly compared to the one with the self-phase
      modulation (SPM) effect. 

PMID- 24922223
TI  - Spatially compressed dual-wavelength excitation Raman spectrometer.
AB  - The design and operation of a novel dual-laser excitation Raman instrument is
      described. The use of two lasers of differing wavelengths allows for a Raman
      spectrum covering all fundamental modes of vibration to be collected while
      minimizing fluorescence and allowing for spatial compression of the spectrum on
      an imaging detector. The use of diode lasers with integrated distributed Bragg
      reflector gratings facilitates the use of an integrated thermoelectric cooler to
      allow collection of shifted excitation spectra for both of the lasers, further
      enhancing the rejection of fluorescence. An example is given, which uses seven
      excitation wavelengths for each laser to reconstruct the Raman spectrum of a
      solvent in the presence of a highly fluorescent dye by using a sequentially
      shifted excitation Raman reconstruction algorithm. 

PMID- 24922224
TI  - High-resolution wide-dynamic range electronically scanned white-light
      interferometry.
AB  - A novel high-resolution wide-dynamic range electronically scanned white-light
      interferometry-based interrogation technique is presented. By using off-the-shelf
      optical components, this technique is capable of reaching a subnanometer
      resolution. The technique relies on a simple optical setup in which the wedge and
      camera axes are mutually inclined for a very small angle in the horizontal plane
      and two-dimensional fringe pattern analysis. Resolution below 0.3 nm and dynamic
      range of 106 dB have been achieved with a signal-to-noise ratio lower than 25 dB.

PMID- 24922225
TI  - Thermal-dynamical analysis of blister formation in chirped mirror irradiated by
      single femtosecond lasers.
AB  - The laser-induced damage behaviors of chirped mirrors (CMs) are studied by single
      800 nm, 38 fs lasers. The CMs provide group delay dispersion of around -60  fs2
      and average reflectivity of about 99.4% with bandwidth range of 200-300 nm at a
      central wavelength of 800 nm. Interestingly, a circular blister feature appears
      in the CMs at a wide range of laser fluence. An optical microscope, atomic force
      microscope, scanning electron microscope, and surface profiler are applied to
      describe the blister characteristics. An adiabatic expansion model of ideal gas
      is adopted to illustrate the formation dynamics of blisters. The evolution of
      blisters can be explained by partial evaporation of the film and a subsequent gas
      expansion, driving the bulging of the film stack up to the stress limit, where
      the blister fractures. According to this model, the energy absorption ratio of
      blisters increases monotonously with increasing laser fluence before the
      occurrence of the focal spot confinement effect.

PMID- 24922226
TI  - Generation of multiterawatt vortex laser beams.
AB  - We report the fabrication of large-area phase masks on thin fused-silica
      substrates that are suitable for shaping multiterawatt femtosecond laser beams.
      We apply these phase masks for the generation of intense femtosecond optical
      vortices. We further quantify distortions of the vortex beam patterns that result
      from several common types of mask defects. 

PMID- 24922227
TI  - Rugate filters used in slit-lamp delivery to improve color rendering of
      illumination for retinal photocoagulation.
AB  - Laser filters and color filters used in slit-lamp delivery have been developed by
      the rugate approach to improve color rendering of illumination for retinal
      photocoagulation. The double-notch laser filter is designed according to the
      required laser lines and incident angle. Based on the transmission spectrum of a
      double-notch laser filter and the spectral power distribution (SPD) of the light
      source of a slit lamp, a scanning search algorithm is applied to find the optimal
      transmission spectrum of a multi-notch color filter for the best color rendering
      index of illumination. Open-source software is used to design the refractive
      index profile of the rugate filters, which are deposited by the reactive pulse
      magnetron sputtering. Both the theoretical analysis of SPD of slitlamp delivery
      with consideration of the deposited rugate filters and the experimental results
      demonstrate that the color rendering property of illumination can be improved
      remarkably, thus making fundus observation and retinal laser photocoagulation
      more reliable and efficient. 

PMID- 24922228
TI  - Design of a lens-to-channel waveguide system as a solar concentrator structure.
AB  - We present a lens-to-channel waveguide solar concentrator, where the lens array
      and the channel waveguide act as the primary and the secondary concentrator.
      Sunlight collected by the lens array is coupled into channel waveguides and exits
      from one end of the tapered waveguide directly onto photovoltaic cells. A 45
      degrees coupler is placed at each lens focal point to couple light into the
      waveguides. This configuration eliminates any inherent decoupling losses. We
      provide a detailed math model and simulation results using exemplar system
      parameters, showing that this structure can achieve 800x concentration at 89.1%
      optical efficiency under +/-0.7 degrees  incidence angle. 

PMID- 24922229
TI  - Improving performances of Fresnel CPV systems: Fresnel-RXI Kohler concentrator.
AB  - The optical design presented here has been done in order to achieve superior
      optical performance in comparison with the state-of-the-art Fresnel CPV systems.
      The design consists of a Photovoltaic Concentrator (CPV) comprising a Fresnel
      lens (F) as a Primary Optical Element (POE) and a dielectric solid RXI as a
      Secondary Optical Element (SOE), both with free-form surfaces (i.e. neither
      rotational nor linearly symmetric). It is the first time the RXI-type geometry
      has been applied to a CPV secondary. This concentrator has ultra-high CAP value
      ready to accommodate more efficient cells eventually to be developed and used
      commercially in future. 

PMID- 24922230
TI  - Dish-based high concentration PV system with Kohler optics.
AB  - We present work at the Steward Observatory Solar Lab on a high concentration
      photovoltaic system in which sunlight focused by a single large paraboloidal
      mirror powers many small triple-junction cells. The optical system is of the XRX
      Kohler type, comprising the primary reflector (X) and a ball lens (R) at the
      focus that reimages the primary reflector onto an array of small reflectors (X)
      that apportion the light to the cells. We present a design methodology that
      provides generous tolerance to mis-pointing, uniform illumination across
      individual cells, minimal optical loss and even distribution between cells, for
      efficient series connection. An operational prototype has been constructed with a
      3.3m x 3.3m square primary reflector of 2m focal length powering 36 actively
      cooled triple-junction cells at 1200x concentration (geometric). The measured end
      to-end system conversion efficiency is 28%, including the parasitic loss of the
      active cooling system. Efficiency ~32% is projected for the next system. 

PMID- 24922231
TI  - Enhanced photocarrier generation in large-scale photonic nanostructures
      fabricated from vertically aligned quantum dots.
AB  - We demonstrate enhanced photocarrier generation using photonic nanostructures
      fabricated by a wet etching technique with vertically aligned quantum dots (QDs).
      Using photoluminescence excitation spectroscopy, we found that the photocarrier
      generation in Ge/Si QDs placed close to the surface is enhanced below the band
      gap energy of crystalline silicon. The enhancement is explained by light trapping
      owing to the photonic nanostructures. Electromagnetic wave simulations indicate
      that the photonic nanostructure with a subwavelength size will be available to
      light trapping for efficient photocarrier generation by increasing their dip
      depth. 

PMID- 24922232
TI  - A two-step design method for high compact rotationally symmetric optical system
      for LED surface light source.
AB  - A two-step optimization method is proposed to design a compact single-surface far
      field illumination system, satisfying the requirements of illuminance uniformity
      and light control efficiency with h/D less than 3:1. In the first step, the
      conventional tailored edge-ray design (TED) method is employed to generate
      prescribed illumination distribution for the rotationally symmetric optical
      system, and an optimization process is added to reach a balance between
      illuminance uniformity and light control efficiency. Based on the improved TED
      method, we can construct an initial optical system more accurate than that
      obtained by point source assumption. In the second step, an iterative feedback
      modification process is employed to optimize the initial optical system, so that
      the degradation of performance due to insufficient control of skew rays is
      mitigated. Because the initial optical system constructed in the first step is
      accurate enough, the second-step feedback modification can converge to a
      satisfactory result within several iterations. As an example, a free-form
      rotationally symmetric lens with the height of h = 25 mm is designed for a
      discoidal LED source with the diameter of D = 10 mm. Both high illuminance
      uniformity of 0.75 and high light control efficiency of 0.86 are obtained
      simultaneously. The method can be further used to achieve more complex non
      uniform illumination distributions. The design of an optical system with h/D =
      2.5:1 and a circular linear illumination distribution is demonstrated. 

PMID- 24922233
TI  - GRIN planar waveguide concentrator used with a single axis tracker.
AB  - It is generally accepted that small to medium level concentrators could be used
      as cost-competitive replacements for tracked solar panels. The objective is to
      design a system that can reach a good level of sun concentration with only one
      sun-tracking axis and is cheap to fabricate. As the most critical parameter for
      all concentrator designs, optical efficiency needed improvement to reduce the
      cost of power produced by our system. By using a graded-index planar waveguide
      with an index profile similar to SELFOC fiber, the ray's path can be controlled.
      Also, the concentrator can be fabricated in a single block, which reduces Fresnel
      reflections. Overall, the optical efficiency can be improved by as much as 33%
      compared to the same system made with a homogeneous waveguide. Furthermore, the
      ability to cost-effectively fabricate the concentrator by molding can be
      preserved, making it possible to reduce the cost of the solar power produced. 

PMID- 24922234
TI  - Light trapping in a polymer solar cell by tailored quantum dot emission.
AB  - We propose a polymer photovoltaic device with a new scattering mechanism based on
      photon absorption and re-emission in a quantum dot layer. A matrix of aluminum
      nanorods with optimized radius and period are used to modify the coupling of
      light emitted from the quantum dots into the polymer layer. Our analysis shows
      that this architecture is capable of increasing the absorption of an ordinary
      polymer photovoltaic device by 28%. 

PMID- 24922235
TI  - Spatio-temporal dynamics behind the shock front from compacted metal nanopowders.
AB  - Laser ablated shock waves from compacted metal nanoenergetic powders of Aluminum
      (Al), Nickel coated Aluminum (Ni-Al) was characterized using shadowgraphy
      technique and compared with that from Boron Potassium Nitrate (BKN), Ammonium
      Perchlorate (AP) and Potassium Bromide (KBr) powders. Ablation is created by
      focused second harmonic (532 nm, 7 ns) of Nd:YAG laser. Time resolved
      shadowgraphs of propagating shock front and contact front revealed dynamics and
      the precise time of energy release of materials under extreme ablative pressures.
      Among the different compacted materials studied, Al nanopowders have maximum
      shock velocity and pressure behind the shock front compared to others. 

PMID- 24922236
TI  - Red-emitting silicon quantum dot phosphors in warm white LEDs with excellent
      color rendering.
AB  - We demonstrate red-emitting silicon quantum dot (SiQD) phosphors as a low-cost
      and environment-friendly alternative to rare-earth element phosphors or CdSe
      quantum dots. After surface passivation, the SiQD-phosphors achieve high
      photoluminescence quantum yield = 51% with 365-nm excitation. The phosphors also
      have a peak photoluminescence wavelength at 630 nm and a full-width-at-half
      maximum of 145 nm. The relatively broadband red emission is ideal for forming the
      basis of a warm white spectrum. With 365-nm or 405-nm LED pumping and the
      addition of green- and/or blue-emitting rare-earth element phosphors, warm white
      LEDs with color rendering index ~95 have been achieved. 

PMID- 24922237
TI  - Imperfectly geometric shapes of nanograting structures as solar absorbers with
      superior performance for solar cells.
AB  - The expectation of perfectly geometric shapes of subwavelength grating (SWG)
      structures such as smoothness of sidewalls and sharp corners and nonexistence of
      grating defects is not realistic due to micro/nanofabrication processes. This
      work numerically investigates optical properties of an optimal solar absorber
      comprising a single-layered silicon (Si) SWG deposited on a finite Si substrate,
      with a careful consideration given to effects of various types of its imperfect
      geometry. The absorptance spectra of the solar absorber with different geometric
      shapes, namely, the grating with attached nanometer-sized features at the top and
      bottom of sidewalls and periodic defects within four and ten grating periods are
      investigated comprehensively. It is found that the grating with attached features
      at the bottom absorbs more energy than both the one at the top and the perfect
      grating. In addition, it is shown that the grating with defects in each fourth
      period exhibits the highest average absorptance (91%) compared with that of the
      grating having defects in each tenth period (89%), the grating with attached
      features (89%), and the perfect one (86%). Moreover, the results indicate that
      the absorptance spectrum of the imperfect structures is insensitive to angles of
      incidence. Furthermore, the absorptance enhancement is clearly demonstrated by
      computing magnetic field, energy density, and Poynting vector distributions. The
      results presented in this study prove that imperfect geometries of the
      nanograting structure display a higher absorptance than the perfect one, and
      provide such a practical guideline for nanofabrication capabilities necessary to
      be considered by structure designers. 

PMID- 24922238
TI  - Compound biomimetic structures for efficiency enhancement of Ga0.5In0.5P/GaAs/Ge
      triple-junction solar cells.
AB  - Biomimetic nanostructures have shown to enhance the optical absorption of
      Ga0.5In0.5P/GaAs/Ge triple junction solar cells due to excellent antireflective
      (AR) properties that, however, are highly dependent on their geometric
      dimensions. In practice, it is challenging to control fabrication conditions
      which produce nanostructures in ideal periodic arrangements and with tapered side
      wall profiles, leading to sacrificed AR properties and solar cell performance. In
      this work, we introduce compound biomimetic nanostructures created by depositing
      a layer of silicon dioxide (SiO2) on top of titanium dioxide (TiO2)
      nanostructures for triple junction solar cells. The device exhibits
      photogenerated current and power conversion efficiency that are enhanced by ~8.9%
      and ~6.4%, respectively, after deposition due to their improved antireflection
      characteristics. We further investigate and verify the optical properties of
      compound structures via a rigorous coupled wave analysis model. The additional
      SiO2 layer not only improves the geometric profile, but also serves as a double
      layer dielectric coating. It is concluded that the compound biomimetic
      nanostructures exhibit superior AR properties that are relatively insensitive to
      fabrication constraints. Therefore, the compound approach can be widely adopted
      for versatile optoelectronic devices and applications.

PMID- 24922239
TI  - Aluminum plasmonic nanoparticles enhanced dye sensitized solar cells.
AB  - We present an investigation on utilizing plasmonic aluminium (Al) nanoparticles
      (NPs) to enhance the optical absorption of dye-sensitized solar cells (DSCs). The
      Al NPs exhibit not only the light absorption enhancement in solar cells with
      localized surface plasmon (LSP) effect but also the chemical stability to
      iodide/triiodide electrolyte. Besides, the lower work function (~4.06 eV),
      compared with that of TiO2 (~4.6 eV), may suppress the quenching processes, such
      as charge transfer to metal NPs, to reduce the loss. Thus, high concentration of
      Al NPs could be incorporated into the TiO2 anodes, and the power conversion
      efficiency (PCE) of DSCs is improved by nearly 13%. Moreover, electrochemical
      impedance spectroscopy (EIS) characterization also indicates that the plasmonic
      DSCs with Al NPs present better electrochemical performance than regular ones,
      which contributes to the improvement of PCE of the device.

PMID- 24922240
TI  - Optimization and analysis of 3D nanostructures for power-density enhancement in
      ultra-thin photovoltaics under oblique illumination.
AB  - Nanostructures have the potential to significantly increase the output power
      density of ultra-thin photovoltaic devices by scattering incident sunlight into
      resonant guided modes. We applied a modified version of the direct-binary-search
      algorithm to design such nanostructures in order to maximize the output power
      density under oblique-illumination conditions. We show that with appropriate
      design of nanostructured cladding layers, it is possible for a 10nm-thick organic
      absorber to produce an average peak power-density of 4 mW/cm2 with incident polar
      angle ranging from -90 degrees  to 90 degrees  and incident azimuthal angle
      ranging from -23.5 degrees  to 23.5 degrees . Using careful modal and spectral
      analysis, we further show that an optimal trade-off of absorption at lambda~510
      nm among various angles of incidence is essential to excellent performance under
      oblique illumination. Finally, we show that the optimized device with no sun
      tracking can produce on an average 7.23 times more energy per year than that
      produced by a comparable unpatterned device with an optimal anti-reflection
      coating.

PMID- 24922241
TI  - Optical properties of nanopillar AlGaN/GaN MQWs for ultraviolet light-emitting
      diodes.
AB  - Nanopillar AlGaN/GaN multiple quantum wells ultraviolet light-emitting diodes
      (LEDs) were fabricated by nanosphere lithography and dry-etching. The optical
      properties of the nanopillar LEDs were characterized by both temperature
      dependent and time-resolved photoluminescence measurements. Compared to an as
      grown sample, the nanopillar sample has a PL emission peak blue-shift of 7 meV, a
      42% enhanced internal quantum efficiency at room temperature and a reduced
      radiative recombination lifetime from 870 picosecond to 621 picosecond at 7K.
      These results are directly from the suppressed quantum confined stark effect that
      is due to the strain relaxation in the nanopillar MQWs, further revealed by micro
      Raman measurement. Additionally, finite-difference time domain simulation also
      proves better light extraction efficiency in the nanopillar LEDs. 

PMID- 24922242
TI  - Electrochemically synthesized broadband antireflective and hydrophobic GaOOH
      nanopillars for III-V InGaP/GaAs/Ge triple-junction solar cell applications.
AB  - We report the efficiency enhancement of III-V InGaP/GaAs/ Ge triple-junction (TJ)
      solar cells using a novel structure, i.e., vertically-oriented gallium oxide
      hydroxide (GaOOH) nanopillars (NPs), as an antireflection coating. The optical
      reflectance properties of rhombus-shaped GaOOH NPs, which were synthesized by a
      simple, low-cost, and large-scalable electrochemical deposition method, were
      investigated, together with a theoretical analysis using the rigorous coupled
      wave analysis method. For the GaOOH NPs, the solar weighted reflectance of ~8.5%
      was obtained over a wide wavelength range of 300-1800 nm and their surfaces
      exhibited a high water contact angle of ~130 degrees  (i.e., hydrophobicity). To
      simply demonstrate the feasibility of device applications, the GaOOH NPs were
      incorporated into a test-grown InGaP/GaAs/Ge TJ solar cell structure. For the
      InGaP/GaAs/Ge TJ solar cell with broadband antireflective GaOOH NPs, the
      conversion efficiency (eta) of ~16.47% was obtained, indicating an increased
      efficiency by 3.47% compared to the bare solar cell (i.e., eta~13%). 

PMID- 24922243
TI  - Dual-band infrared perfect absorber based on asymmetric T-shaped plasmonic array.
AB  - An infrared dual-band perfect absorber based on asymmetric T-shaped plasmonic
      array is designed and numerically investigated. Two distinct absorption peaks are
      achieved by localized surface plasmon polariton (LSPP) mode over a wide incident
      angular range. Both the absorption peaks can be finely tuned independently by
      varying the geometry of the structure. In our proposed structure, the period of
      the T-shaped structures becomes less and the multiple LSPP peaks are suppressed,
      which result in the sideband of absorption peaks very low. This dual-band perfect
      absorber has potential applications such as in infrared imaging devices, thermal
      bolometers, and wavelength selective radiators. 

PMID- 24922244
TI  - Performance-limiting factors for GaAs-based single nanowire photovoltaics.
AB  - GaAs nanowires (NWs) offer the possibility of decoupling light absorption from
      charge transport for high-performance photovoltaic (PV) devices. However, it is
      still an open question as to whether these devices can exceed the Shockley
      Queisser efficiency limit for single-junction PV. In this work, single standing
      GaAs-based nanowire solar cells in both radial and vertical junction
      configurations is analyzed and compared to a planar thin-film design. By using a
      self-consistent, electrical-optically coupled 3D simulator, we show the design
      principles for nanowire and planar solar cells are significantly different;
      nanowire solar cells are vulnerable to surface and contact recombination, while
      planar solar cells suffer significant losses due to imperfect backside mirror
      reflection. Overall, the ultimate efficiency of the GaAs nanowire solar cell with
      radial and vertical junction is not expected to exceed that of the thin-film
      design, with both staying below the Shockley-Queisser limit. 

PMID- 24922245
TI  - Type II GaSb quantum ring solar cells under concentrated sunlight.
AB  - A type II GaSb quantum ring solar cell is fabricated and measured under the
      concentrated sunlight. The external quantum efficiency confirms the extended
      absorption from the quantum rings at long wavelength coinciding with the
      photoluminescence results. The short-circuit current of the quantum ring devices
      is 5.1% to 9.9% more than the GaAs reference's under various concentrations.
      While the quantum ring solar cell does not exceed its GaAs counterpart in
      efficiency under one-sun, the recovery of the open-circuit voltages at higher
      concentration helps to reverse the situation. A slightly higher efficiency
      (10.31% vs. 10.29%) is reported for the quantum ring device against the GaAs one.

PMID- 24922246
TI  - Side-illuminating LED luminaires with accurate projection in high uniformity and
      high optical utilization factor for large-area field illumination.
AB  - A novel light luminaire is proposed and experimentally analyzed, which accurately
      projects light into a large rectangular area to achieve uniform illumination and
      a high optical utilization factor at the target. Side-illuminating luminaires for
      large-scale illuminated area are typically set with an elevated tilt angle to
      enlarge the illuminated area. However, the light pattern is bent thereby reducing
      the uniformity and optical utilization factor at the target. In this paper, we
      propose an efficient and useful approach with a rotationally symmetric projection
      lens that is trimmed to adjust the bending effect and to form a rectangular
      illumination light pattern on the ground. The design concept is demonstrated and
      verified. Several potential applications such as highly uniform illumination with
      fitting shapes for sport courts are analyzed and discussed. 

PMID- 24922247
TI  - High-efficiency, broad-band and wide-angle optical absorption in ultra-thin
      organic photovoltaic devices.
AB  - Metal nanogratings as one of the promising architectures for effective light
      trapping in organic photovoltaics (OPVs) have been actively studied over the past
      decade. Here we designed a novel metal nanowall grating with ultra-small period
      and ultra-high aspect-ratio as the back electrode of the OPV device. Such grating
      results in the strong hot spot effect in-between the neighboring nanowalls and
      the localized surface plasmon effect at the corners of nanowalls. These combined
      effects make the integrated absorption efficiency of light over the wavelength
      range from 400 to 650 nm in the active layer for the proposed structure, with
      respect to the equivalent planar structure, increases by 102% at TM polarization
      and by 36.5% at the TM/TE hybrid polarization, respectively. Moreover, it is
      noted that the hot spot effect in the proposed structure is more effective for
      ultra-thin active layers, which is very favorable for the exciton dissociation
      and charge collection. Therefore such a nanowall grating is expected to improve
      the overall performance of OPV devices. 

PMID- 24922248
TI  - Strong broadband absorption in GaAs nanocone and nanowire arrays for solar cells.
AB  - We studied the influence of geometric parameters on the optical absorption of
      gallium arsenide (GaAs) nanocone and nanowire arrays via finite difference time
      domain simulations. We optimized the structural parameters of the nanocone and
      nanowire arrays to maximize the ultimate efficiency across a range of lengths
      from 100 to 1000 nm. Nanocone arrays were found to have improved solar
      absorption, short-circuit current density, and ultimate efficiencies over
      nanowire arrays for a wide range of lengths. Detailed simulations reveal that
      nanocones have superior absorption due to reduced reflection from their smaller
      tip and reduced transmission from their larger base. Breaking the vertical mirror
      symmetry of nanowires results in a broader absorption spectrum such that overall
      efficiencies are enhanced for nanocones. We also evaluated the electric field
      intensity, carrier generation and angle-dependent optical properties of nanocones
      and nanowires. The carrier generation in nanocone arrays occurs away from the
      surface and is more uniform over the entire structure, which should result in
      less recombination losses than in nanowire arrays. 

PMID- 24922249
TI  - GaN-based light-emitting diodes with graphene/indium tin oxide transparent layer.
AB  - We have demonstrated a gallium nitride (GaN)-based green light-emitting diode
      (LED) with graphene/indium tin oxide (ITO) transparent contact. The ohmic
      characteristic of the p-GaN and graphene/ITO contact could be preformed by
      annealing at 500  degrees C for 5 min. The specific contact resistance of p
      GaN/graphene/ITO (3.72E-3 Omega.cm2) is one order less than that of p-GaN/ITO. In
      addition, the 20-mA forward voltage of LEDs with graphene/ITO transparent (3.05
      V) is 0.09 V lower than that of ITO LEDs (3.14 V). Besides, We have got an output
      power enhancement of 11% on LEDs with graphene/ITO transparent contact.

PMID- 24922250
TI  - Reflectance properties of silicon moth-eyes in response to variations in angle of
      incidence, polarisation and azimuth orientation.
AB  - We report a study of the optical properties of silicon moth-eye structures using
      a custom-made fully automated broadband spectroscopic reflectometry system
      (goniometer). This measurement system is able to measure specular reflectance as
      a function of wavelength, polar incidence angle and azimuth orientation angle,
      from normal to near-parallel polar incidence angle. The system uses a linear
      polarized broadband super-continuum laser light source. It is shown that a moth
      eye structure composed of a regular array of protruding silicon rods, with finite
      sidewall angle reduces reflectance and sensitivity to incident wavelength in
      comparison to truly cylindrical rods with perpendicular sidewalls. It is also
      shown that moth-eye structures have omnidirectional reflectance properties in
      response to azimuth orientation of the sample. The importance of applying the
      reflectometer setup to study the optical properties of solar cell antireflective
      structures is highlighted. 

PMID- 24922251
TI  - Optical properties associated with strain relaxations in thick InGaN epitaxial
      films.
AB  - Structural and optical properties of thick InGaN layers with strain and
      composition inhomogeneities are investigated. High resolution x-ray diffractions
      (XRD) and reciprocal space mapping (RSM) along an asymmetric axis reveal that the
      In composition inhomogeneity is accompanied by strain relaxations during the
      growth of thick InGaN layers. According to the structural analysis, the commonly
      observed double photoluminescence (PL) peaks have been confirmed to be associated
      with the strain relaxation in thick InGaN films. Temperature-dependent PL
      measurements further indicate that the relaxed phase in InGaN films exhibits
      better emission efficiency than the strained phase. Recombination dynamics reveal
      that the carrier localization effect is more pronounced in the relaxed phase due
      to the compositional pulling effect. The correlations between emission efficiency
      and localization effect in thick InGaN films are discussed. 

PMID- 24922252
TI  - A study on the optics of copper indium gallium (di)selenide (CIGS) solar cells
      with ultra-thin absorber layers.
AB  - We present a systematic study of the effect of variation of the zinc oxide (ZnO)
      and copper indium gallium (di)selenide (CIGS) layer thickness on the absorption
      characteristics of CIGS solar cells using a simulation program based on finite
      element method (FEM). We show that the absorption in the CIGS layer does not
      decrease monotonically with its layer thickness due to interference effects.
      Ergo, high precision is required in the CIGS production process, especially when
      using ultra-thin absorber layers, to accurately realize the required thickness of
      the ZnO, cadmium sulfide (CdS) and CIGS layer. We show that patterning the ZnO
      window layer can strongly suppress these interference effects allowing a higher
      tolerance in the production process. 

PMID- 24922253
TI  - Plasmonic ITO-free polymer solar cell.
AB  - The aluminum and sliver multilayered nano-grating structure is fabricated by
      laser interference lithography and the intervals between nanoslits is filled with
      modified PEDOT:PSS. The grating structured transparent electrode functions as the
      anti-reflection layer which not only decreases the reflected light but also
      increases the absorption of the active layer. The performances of P3HT:PC61BM
      solar cells are studied experimentally and theoretically in detail. The field
      intensities of the transverse magnetic (TM) and transverse electrical (TE) waves
      distributed in the active layer are simulated by rigorous coupled wave analysis
      (RCWA). The power conversion efficiency of the plasmonic ITO-free polymer solar
      cell can reach 3.64% which is higher than ITO based polymer solar cell with
      efficiency of 3.45%.

PMID- 24922254
TI  - A study on luminescence properties and energy transfer mechanism for
      NaCaY(PO4)2:Eu2+,Mn2+ phosphors for LED applications.
AB  - A color-tunable NaCaY(PO4)2:Eu2+,Mn2+, was synthesized by a solid state reaction.
      NaCaY(PO4)2 crystallizes in the hexagonal structure system with space group of
      P6222 and Z = 1. The NaCaY(PO4)2:Eu2+ exhibits blue-greenish emission and broad
      excitation bands corresponding to the allowed f->d electronic transition of Eu2+.
      In addition, via the design of efficient energy transfer from Eu2+ to Mn2+, a
      high quality of white-emitting light could be generated in the optimized
      composition of NaCaY(PO4)2:1%Eu2+, 0.5%Mn2+ with CIE coordinates of
      (0.3389,0.3531) and CRI of 82, which is superior than that of blue chip and YAG
      phosphors. The results indicate that as-synthesized NaCaY(PO4)2:Eu2+,Mn2+
      phosphors exhibits the potential to be an n-UV convertible phosphor.

PMID- 24922255
TI  - Enhanced up-conversion for photovoltaics via concentrating integrated optics.
AB  - Concentrating optics are integrated into up-conversion photovoltaic (UC-PV)
      devices to independently concentrate sub-band-gap photons on the up-conversion
      layer, without affecting the full solar concentration on the overlying solar
      cell. The UC-PV devices consist of silicon solar cells optimized for up
      conversion, coupled with tapered and parabolic dielectric concentrators, and
      hexagonal sodium yttrium fluoride (beta-NaYF4) up-converter doped with 25%
      trivalent erbium (Er3+). A normalized external quantum efficiency of 1.75x10-2
      cm2/W and 3.38x10-2 cm2/W was obtained for the UC-PV device utilizing tapered and
      parabolic concentrators respectively. Although low to moderate concentration was
      shown to maximize UC, higher concentration lead to saturation and reduced
      external quantum efficiency. The presented work highlights some of the
      implications associated with the development of UC-PV devices and designates a
      substantial step for integration in concentrating PV.

PMID- 24922256
TI  - Light trapping design for low band-gap polymer solar cells.
AB  - We demonstrate numerically a 2-D nanostructured design for light trapping in a
      low band-gap polymer solar cell. Finite element method simulations are used to
      study the effect of varying nanostructure periodicity, height, and shape on
      active layer absorption. Maintaining a constant active layer thickness of 100 nm
      we observe an enhancement in solar absorption of almost 40% relative to a planar
      cell. Improvements of this magnitude enable single-junction, low-band-gap cells
      to achieve power conversion efficiencies of 11.2% and perform competitively with
      even state-of-the-art tandem cells. Our design is also shown to significantly
      outperform tandem cells at off-normal angles of incidence.

PMID- 24922257
TI  - Reduced optical loss in mechanically stacked multi-junction organic solar cells
      exhibiting complementary absorptions.
AB  - This paper describes a promising approach toward preparing effective electrical
      and optical interconnections for tandem organic photovoltaic devices (OPVs). The
      first subcell featured a semi-transparent electrode, which allowed a portion of
      the solar irradiation to pass through and to enter the second subcell exhibiting
      complementary absorption behavior. The resulting multi-junction OPV had multiple
      contacts such that the subcells could be easily connected either in series or in
      parallel. More importantly, we used UV-curable epoxy to "mechanically" stack the
      two subcells and to eliminate the air gap between them, thereby reducing the
      optical loss induced by mismatches of refractive indices. Therefore, an improved
      power conversion efficiency of approximately 6.5% has been achieved. 

PMID- 24922258
TI  - Influence of carrier localization on high-carrier-density effects in AlGaN
      quantum wells.
AB  - The influence of carrier localization on photoluminescence efficiency droop and
      stimulated emission is studied in AlGaN multiple quantum wells with different
      strength of carrier localization. We observe that carrier delocalization at low
      temperatures predominantly enhances the nonradiative recombination and causes the
      droop, while the main effect of the delocalization at elevated temperatures is
      enhancement of PL efficiency due to increasing contribution of bimolecular
      recombination of free carriers. When the carrier thermal energy exceeds the
      dispersion of the potential fluctuations causing the carrier localization, the
      droop is caused by stimulated carrier recombination. 

PMID- 24922259
TI  - Proof of principle demonstration of a self-tracking concentrator.
AB  - We present to the best of our knowledge the first successful demonstration of a
      planar, self-tracking solar concentrator system capable of a 2-dimensional
      angular acceptance of over 40 degrees . The light responsive mechanism allows for
      efficient waveguide coupling and light concentration independently of the angle
      of incidence within the angular range. A coupling feature is created at the focal
      spot of the optical system by locally melting a phase change material which acts
      as an actuator due to the large thermal expansion. A dichroic prism membrane
      reflects the visible light so that it is efficiently coupled into a waveguide at
      the point of the created coupling feature. We show simulation results for
      concentration and efficiency, validated by an experimental proof of concept
      demonstration of a self-tracking concentrator array element. Simulations show
      that a system based on this approach can achieve 150X effective concentration by
      scaling the system collecting area to reasonable dimensions (40 x 10 cm2).

PMID- 24922260
TI  - Color-by-blue display using blue quantum dot light-emitting diodes and green/red
      color converting phosphors.
AB  - We report a novel full-color display based on the generation of full-color by a
      highly efficient blue QD-LED light approach, or so called color-by-blue QD-LED
      display. This newly proposed color-by-blue QD-LED display combines a blue
      CdZnS/ZnS QD-LED blue subpixel and excitation source with front-emitting
      green/red phosphor subpixels. It is carefully estimated that the detailed display
      characteristics as well as full color-conversion and reasonable device efficiency
      of blue, green, and red satisfy the minimum requirements for display application.
      Also, we would like to emphasize that the proposed blue, green, and red device
      shows maximum luminance of 1570, 12920, and 3120 cd/m2, respectively, luminous
      efficiency of 1.5, 12.1, and 2.5 cd/A, respectively, and external quantum
      efficiency of 6.8, 2.8, and 2.0%, respectively. It is expected that full color
      generation by color-by-blue QD-LED will lead to further technological
      advancements in the area of efficient and facile display applications.

PMID- 24922261
TI  - Micro-concentrators for a microsystems-enabled photovoltaic system.
AB  - A 100X magnification, +/- 2.5 degrees  field of view micro-concentrating optical
      system has been developed for a microsystems-enabled photovoltaic (MEPV)
      prototype module using 250 um diameter multi-junction "stacked" PV cells. 

PMID- 24922262
TI  - Spectrum splitting metrics and effect of filter characteristics on photovoltaic
      system performance.
AB  - During the past few years there has been a significant interest in spectrum
      splitting systems to increase the overall efficiency of photovoltaic solar energy
      systems. However, methods for comparing the performance of spectrum splitting
      systems and the effects of optical spectral filter design on system performance
      are not well developed. This paper addresses these two areas. The system
      conversion efficiency is examined in detail and the role of optical spectral
      filters with respect to the efficiency is developed. A new metric termed the
      Improvement over Best Bandgap is defined which expresses the efficiency gain of
      the spectrum splitting system with respect to a similar system that contains the
      highest constituent single bandgap photovoltaic cell. This parameter indicates
      the benefit of using the more complex spectrum splitting system with respect to a
      single bandgap photovoltaic system. Metrics are also provided to assess the
      performance of experimental spectral filters in different spectrum splitting
      configurations. The paper concludes by using the methodology to evaluate spectrum
      splitting systems with different filter configurations and indicates the overall
      efficiency improvement that is possible with ideal and experimental designs. 

PMID- 24922263
TI  - How to assess light trapping structures versus a Lambertian Scatterer for solar
      cells?
AB  - We propose a new figure of merit to assess the performance of light trapping
      nanostructures for solar cells, which we call the light trapping efficiency
      (LTE). The LTE has a target value of unity to represent the performance of an
      ideal Lambertian scatterer, although this is not an absolute limit but rather a
      benchmark value. Since the LTE aims to assess the nanostructure itself, it is, in
      principle, independent of the material, fabrication method or technology used. We
      use the LTE to compare numerous proposals in the literature and to identify the
      most promising light trapping strategies. We find that different types of
      photonic structures allow approaching the Lambertian limit, which shows that the
      light trapping problem can be approached from multiple directions. The LTE of
      theoretical structures significantly exceeds that of experimental structures,
      which highlights the need for theoretical descriptions to be more comprehensive
      and to take all relevant electro-optic effects into account. 

PMID- 24922264
TI  - Designing optical free-form surfaces for extended sources.
AB  - LED lighting has been a strongly growing field for the last decade. The
      outstanding features of LED, like compactness and low operating temperature take
      the control of light distributions to a new level. Key for this is the
      development of sophisticated optical elements that distribute the light as
      intended. The optics design method known as tailoring relies on the point source
      assumption. This assumption holds as long as the optical element is large
      compared to the LED chip. With chip sizes of 1 mm2 this is of no concern if each
      chip is endowed with its own optic. To increase the power of a luminaire, LED
      chips are arranged to form light engines that reach several cm in diameter. In
      order to save costs and space it is often desirable to use a single optical
      element for the light engine. At the same time the scale of the optics must not
      be increased in order to trivially keep the point source assumption valid. For
      such design tasks point source algorithms are of limited usefulness. New methods
      that take into account the extent of the light source have to be developed. We
      present two such extended source methods. The first method iteratively adapts the
      target light distribution that is fed into a points source method while the
      second method employs a full phase space description of the optical system.

PMID- 24922266
TI  - Focus issue introduction: Laser Ignition Conference.
AB  - The purpose of this feature issue is to share information on laser ignition and
      related sciences and technologies. This feature offers five papers in the field
      that cover aspects of laser-induced laser ignition, including novel giant pulse
      micro-lasers, new phenomena of laser breakdown, advanced combustion systems and
      applications. These topics were chosen from the first Laser Ignition Conference
      (LIC) covering the topics of high brightness lasers for ignition and diagnostics,
      laser ignited engines for power generators and vehicles, and from a joint
      symposium with the Laser Display Conference covering applications of high
      brightness lasers. 

PMID- 24922267
TI  - A hybrid simulated method for analyzing the optical efficiency of a head-mounted
      display with a quasi-crystal OLED panel.
AB  - Organic light emitting diodes (OLEDs) with a quasi-crystal (QC) structure are
      analyzed and applied in a head-mounted display (HMD) system in this study. We
      adopt a hybrid simulated method to evaluate the light extraction efficiency (LEE)
      and far-field pattern in the air, and study the relationship between them. The
      simulation results show that OLEDs implanted with the QC structure can provide a
      collimated far-field pattern to increase the brightness. Using this 10-fold QC
      arrangement the maxima LEE of the OLEDs can be increased by 1.20 times. Compared
      with conventional OLEDs, the viewing angle of the OLED panel decreases from 120
      degrees to 26 degrees with an improvement in the optical efficiency of the HMD
      system by 2.66 times. Moreover, the normalized on-axis intensity in the pupil of
      the eyepiece can be enlarged up to 3.95 times which suggests that the OLED panel
      can save 74.68% energy while achieving the same on-axis intensity as conventional
      OLEDs. 

PMID- 24922268
TI  - Relation of immune semaphorin/plexin signaling to carcinogenesis.
AB  - Semaphorins and plexins represent a highly conserved group of proteins that have
      recently been found to exert widespread regulatory functions outside the nervous
      system, including angiogenesis and immune regulation. Furthermore, these
      molecules are definitely implicated in the etiology of carcinogenesis and immune
      disorders. Their expression patterns and levels are deregulated in cancer cells
      and in cells of the tumor milieu. During the multistep development of cancer, its
      characteristic features include sustained tumor cell proliferation, resistance to
      cell death, limitless replicative capacity, activation of angiogenesis along with
      invasion and metastatic spread, cancer-related smoldering inflammation, and
      evasion of antitumor immune responses. The diversity of the semaphorin/plexin
      complexes and, thus, the multiple stimulated molecular interactions allow varied
      and diverse cell signaling events. The elicited transduction pathways might be
      involved in modifying the intricate mechanisms of tumorigenesis. Indeed, these
      pleiotropic signals may influence not only the intrinsic properties of cancer
      cells but they could also represent a possible link in mediating the cross-talk
      between tumor cells and the surrounding multiple stromal cells. In tumorigenesis,
      however, a dual role of different semaphorins is proposed, as some of them may
      elicit tumor regression, whereas others definitely promote cancer cell survival
      and progression. The current antitumoral or prosurvival responsiveness to
      semaphorins is mainly cell context dependent; nevertheless, their precise
      relation to cancer networks has not yet been fully elucidated. Here, we survey
      the many faces of a subset of the large semaphorin family, termed immune
      semaphorins, in carcinogenesis. 

PMID- 24922269
TI  - Synthesis of the Pitstop family of clathrin inhibitors.
AB  - This protocol describes the synthesis of two classes of clathrin inhibitors,
      Pitstop 1 and Pitstop 2, along with two inactive analogs that can be used as
      negative controls (Pitstop inactive controls, Pitnot-2 and Pitnot-2-100). Pitstop
      induced inhibition of clathrin TD function acutely interferes with clathrin
      mediated endocytosis (CME), synaptic vesicle recycling and cellular entry of HIV,
      whereas clathrin-independent internalization pathways and secretory traffic
      proceed unperturbed; these reagents can, therefore, be used to investigate
      clathrin function, and they have potential pharmacological applications. Pitstop
      1 is synthesized in two steps: sulfonation of 1,8-naphthalic anhydride and
      subsequent reaction with 4-amino(methyl)aniline. Pitnot-1 results from the
      reaction of 4-amino(methyl)aniline with commercially available 4-sulfo-1,8
      naphthalic anhydride potassium salt. Reaction of 1-naphthalene sulfonyl chloride
      with pseudothiohydantoin followed by condensation with 4-bromobenzaldehyde yields
      Pitstop 2. The synthesis of the inactive control commences with the condensation
      of 4-bromobenzaldehyde with the rhodanine core. Thioketone methylation and
      displacement with 1-napthylamine affords the target compound. Although Pitstop 1
      series compounds are not cell permeable, they can be used in biochemical assays
      or be introduced into cells via microinjection. The Pitstop 2-series compounds
      are cell permeable. The synthesis of these compounds does not require specialist
      equipment and can be completed in 3-4 d. Microwave irradiation can be used to
      reduce the synthesis time. The synthesis of the Pitstop 2 family is easily
      adaptable to enable the synthesis of related compounds such as Pitstop 2-100 and
      Pitnot-2-100. The procedures are also simple, efficient and amenable to scale-up,
      enabling cost-effective in-house synthesis for users of these inhibitor classes. 

PMID- 24922270
TI  - Generation of a transgenic ORFeome library in Drosophila.
AB  - Overexpression screens can be used to explore gene function in Drosophila
      melanogaster, but to demonstrate their full potential, comprehensive and
      systematic collections of fly strains are required. Here we provide a protocol
      for high-throughput cloning of Drosophila open-reading frames (ORFs) that are
      regulated by upstream activation sequences (UAS sites); the resulting GAL4
      inducible UAS-ORF plasmid library is then used to generate Drosophila strains by
      PhiC31 integrase-mediated site-specific integration. We also provide details for
      FLP/FRT-mediated in vivo exchange of epitope tags (or regulatory regions) in the
      ORF library strains, which further extends the potential applications of the
      library. These transgenic UAS-ORF strains are a useful resource to complement and
      validate genetic experiments performed with loss-of-function mutants and RNA
      interference (RNAi) lines. The duration of the complete protocol strongly depends
      on the number of ORFs required, but embryos can be injected and balanced fly
      stocks can be established within ~7-8 weeks for a few genes. 

PMID- 24922271
TI  - Porous nucleating agents for protein crystallization.
AB  - Solving the structure of proteins is pivotal to achieving success in rational
      drug design and in other biotechnological endeavors. The most powerful method for
      determining the structure of proteins is X-ray crystallography, which relies on
      the availability of high-quality crystals. However, obtaining such crystals is a
      major hurdle. Nucleation is the crucial prerequisite step, which requires
      overcoming an energy barrier. The presence in a protein solution of a nucleant, a
      solid or a semiliquid substance that facilitates overcoming that barrier allows
      crystals to grow under ideal conditions, paving the way for the formation of high
      quality crystals. The use of nucleants provides a unique means for optimizing the
      diffraction quality of crystals, as well as for discovering new crystallization
      conditions. We present a protocol for controlling the nucleation of protein
      crystals that is applicable to a wide variety of nucleation-inducing substances.
      Setting up crystallization trials using these nucleating agents takes an
      additional few seconds compared with conventional setup, and it can accelerate
      crystallization, which typically takes several days to months. 

PMID- 24922273
TI  - Insights from arsenate adsorption on rutile (110): grazing-incidence X-ray
      absorption fine structure spectroscopy and DFT+U study.
AB  - Insights into the bonding of As(V) at the metal oxide/aqueous interface can
      further our understanding of its fate and transport in the environment. The
      motivation of this work is to explore the interfacial configuration of As(V) on
      single crystal rutile (110) using grazing-incidence X-ray absorption fine
      structure spectroscopy (GI-XAFS) and planewave density functional calculations
      with on-site repulsion (DFT+U). In contrast to the commonly considered corner
      sharing bidentate binuclear structure, tetrahedral As(V) binds as an edge/corner
      sharing tridentate binuclear complex on rutile (110), as evidenced by observation
      of three As-Ti distances at 2.83, 3.36, and 4.05 A. In agreement with the GI-XAFS
      analysis, our DFT+U calculations for this configuration resulted in the lowest
      adsorption energy among five possible alternatives. In addition, the electron
      density difference further demonstrated the transfer of charge between surface Ti
      atoms and O atoms in AsO4. This charge transfer consequently induced the
      formation of a chemical bond, which is also confirmed by the partial density of
      states analysis. Our results may shed new light on coupling the GI-XAFS and DFT
      approaches to explore molecular-scale adsorption mechanisms on single crystal
      surfaces. 

PMID- 24922272
TI  - Preparation of core-shell NaGdF4 nanoparticles doped with luminescent lanthanide
      ions to be used as upconversion-based probes.
AB  - Sodium gadolinium fluoride (NaGdF4) is an ideal host material for the
      incorporation of luminescent lanthanide ions because of its high photochemical
      stability, low vibrational energy and its ability to mediate energy exchanges
      between the lanthanide dopants. This protocol describes the detailed experimental
      procedure for synthesizing core-shell NaGdF4 nanoparticles that incorporate
      lanthanide ions into different layers for efficiently converting a single
      wavelength, near-IR excitation into a tunable visible emission. These
      nanoparticles can then be used as luminescent probes in biological samples, in 3D
      displays, in solar energy conversion and in photodynamic therapy. The NaGdF4
      nanoparticles are grown through co-precipitation in a binary solvent mixture of
      oleic acid and 1-octadecene. Doping by lanthanides with controlled compositions
      and concentrations can be achieved concomitantly with particle growth. The
      lanthanide-doped NaGdF4 nanoparticles then serve as seed crystals for subsequent
      epitaxial growth of shell layers comprising different lanthanide dopants. The
      entire procedure for the preparation and isolation of the core-shell
      nanoparticles comprising two epitaxial shell layers requires ~15 h for
      completion. 

PMID- 24922274
TI  - Simultaneous determination of thirteen aminoalcohol-diterpenoid alkaloids in the
      lateral roots of Aconitum carmichaeli by solid-phase extraction-liquid
      chromatography-tandem mass spectrometry.
AB  - Aminoalcohol-diterpenoid alkaloids have been reported as the cardioactive
      components in the lateral roots of Aconitum carmichaeli (Fuzi) according to
      recent studies. Determination of these effective components is of great
      significance for quality control purposes for Fuzi. Here we report, for the
      first, the development and validation of a new method to determine the 13
      aminoalcohol-diterpenoid alkaloids in Fuzi by using a simple and accurate solid
      phase extraction-liquid chromatography-tandem mass spectrometry. The
      chromatographic analysis was performed on an ODS column with methanol-0.1 %
      formic acid (80 : 20, v/v) as the mobile phase. The quantification was performed
      using MS/MS detection in the positive ion mode with multiple reaction monitoring.
      Linearity was observed within a range of concentrations of 20-2,000 ng/mL. For
      all the analytes, the r value was greater than 0.9990. The limit of detection and
      the limit of quantitation were less than 0.5 ng/mL and 2.0 ng/mL, respectively.
      The intraday and interday precisions were less than 5% and 10%, respectively. The
      accuracy was within the range of 90 to 105%. This method was successfully applied
      to determine the 13 aminoalcohol-diterpenoid alkaloids in Fuzi from different
      origins and with different processing methods.

PMID- 24922275
TI  - Human ovarian cancer multicellular spheroids: a model for testing
      antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer
      agents.
AB  - This study was conducted to employ an ovarian cancer Ovcar 10 three-dimensional
      model to assess the antiproliferation activity of the medicinal plant Devil's
      club, Oplopanax horridus, and its active compound, alone and in combination, with
      chemotherapeutic agents compared to Ovcar 10 two-dimensional cells grown as
      monolayer cells. Ovcar 10 three-dimensional spheroids were prepared with a rotary
      cell culture system. Cell counting kit-8 assessed the antiproliferation activity.
      Apoptosis-related gene expression in three-dimensional spheroids and two-
      dimensional cells was analyzed with an apoptosis antibody array. Flow cytometry
      was used to analyze the cell cycle. Ovcar 10 cells formed compact three
      dimensional spheroids after 5 days of culture in a rotary culture system. Ovcar
      10 three-dimensional spheroids were significantly more resistant to killing by
      Devil's club extract, its active compound alone, gemcitabine, and paclitaxel, but
      not cisplatin compared to two-dimensional cells, with IC50 levels closer to that
      observed in vivo. Devil's club extract and its active compound alone
      significantly enhanced the antiproliferation activity of cisplatin and
      gemcitabine at some concentrations, but did not affect the activity of
      paclitaxel. A number of apoptosis-related genes were differentially expressed in
      three-dimensional spheroids, two-dimensional cells, and cells treated with
      Devil's club extract compared to untreated controls. In three-dimensional
      spheroids, the proportion of cells in the G2/M phase was slightly increased and
      the S phase was slightly decreased compared to two-dimensional cells. Ovcar 10
      cells in three-dimensional spheroids altered the expression of multiple apoptosis
      related genes, which may have contributed to the increased resistance of the
      cells to some drugs.

PMID- 24922276
TI  - Useful methods for targeted plant selection in the discovery of potential new
      drug candidates.
AB  - The efficient and effective selection of appropriate plants for investigative
      purposes in a drug discovery program is of crucial importance for a successful
      outcome. A variety of approaches have been used by researchers with varying
      levels of success. A variety of different approaches to plant selection are
      discussed, including the ethnomedicinal approach, some ecological approaches, and
      the use of combinatorial and computational methodologies.

PMID- 24922277
TI  - Meta-analysis of the differentially expressed breast cancer-related microRNA
      expression profiles.
AB  - MicroRNAs (miRNAs), as non-coding RNA molecules, play an important role in
      regulating gene expression in cancer development. Meta-analysis was used to
      screen overlapping differentially expressed miRNAs (DEmiRNAs) in three studies.
      The miRanda was used to identify target genes related to overlapping DEmiRNAs.
      These Gene Ontology (GO) and Encyclopaedia of Genes and Genomes (KEGG) database
      were applied to further predict the function of these target genes. As a result,
      we obtained seven overlapping miRNAs and six significantly over-represented GO
      terms closely related to breast cancer. After KEGG pathways analysis, a total of
      seven key target genes were involved in the Wnt signalling pathway (p = 0.0002).
      Our findings from this study suggest that the altered levels of miRNAs might have
      great potential to serve as novel, non-invasive biomarkers for early detection of
      breast cancer.

PMID- 24922278
TI  - Fast Surface Crystal Growth on Molecular Glasses and Its Termination by the Onset
      of Fluidity.
AB  - Organic glasses can grow crystals much faster on the free surface than in the
      interior, a phenomenon important for fabricating stable amorphous materials. This
      surface process differs from and is faster than the glass-to-crystal (GC) growth
      mode existing in the bulk of molecular glasses. We report that similar to GC
      growth, surface crystal growth terminates if glasses are heated to gain fluidity.
      In their steady growth below the glass transition temperature Tg, surface
      crystals rise above the amorphous surface while spreading laterally and are
      surrounded by depressed grooves. Above Tg, the growth becomes slower, sometimes
      unstable. This damage is stronger on segregated needles (alpha indomethacin,
      nifedipine, and o-terphenyl) than on crystals growing in compact domains (gamma
      indomethacin). This effect arises because the onset of liquid flow causes the
      wetting and embedding of upward-growing surface crystals. Segregated needles are
      at greater risk because their slow-growing flanks appear stationary relative to
      liquid flow at a low temperature. The disruption of surface crystal growth by
      fluidity supports the view that the process occurs by surface diffusion, not
      viscous flow. Compared to the bulk GC mode, surface crystal growth is disrupted
      less abruptly by fluidity. Nevertheless, to the extent that fluidity damages
      them, both processes are solid-state phenomena terminated in the liquid state.

PMID- 24922279
TI  - Hypokalaemia-induced rhabdomyolysis after treatment of post-Kala-azar dermal
      Leishmaniasis (PKDL) with high-dose AmBisome in Bangladesh-a case report.

PMID- 24922280
TI  - Populational survey of arthropods on transgenic common bean expressing the rep
      gene from Bean golden mosaic virus.
AB  - Genetically modified (GM) crops is considered the fastest adopted crop technology
      in the history of modern agriculture. However, possible undesirable and
      unintended effects must be considered during the research steps toward
      development of a commercial product. In this report we evaluated effects of a
      common bean virus resistant line on arthropod populations, considered as non
      target organisms. This GM bean line (named M1/4) was modified for resistance
      against Bean golden mosaic virus (BGMV) by expressing a mutated REP protein,
      which is essential for virus replication. Biosafety studies were performed for a
      period of three years under field conditions. The abundance of some species was
      significantly higher in specific treatments in a particular year, but not
      consistently different in other years. A regular pattern was not observed in the
      distribution of insects between genetically modified and conventional treatments.
      Data analyses showed that minor differences observed can be attributed to random
      variation and were not consistent enough to conclude that the treatments were
      different. Therefore the present study indicates that the relative abundance of
      species are similar in transgenic and non-transgenic fields. 

PMID- 24922282
TI  - Virtual scarce water in China.
AB  - Water footprints and virtual water flows have been promoted as important
      indicators to characterize human-induced water consumption. However,
      environmental impacts associated with water consumption are largely neglected in
      these analyses. Incorporating water scarcity into water consumption allows better
      understanding of what is causing water scarcity and which regions are suffering
      from it. In this study, we incorporate water scarcity and ecosystem impacts into
      multiregional input-output analysis to assess virtual water flows and associated
      impacts among 30 provinces in China. China, in particular its water-scarce
      regions, are facing a serious water crisis driven by rapid economic growth. Our
      findings show that inter-regional flows of virtual water reveal additional
      insights when water scarcity is taken into account. Consumption in highly
      developed coastal provinces is largely relying on water resources in the water
      scarce northern provinces, such as Xinjiang, Hebei, and Inner Mongolia, thus
      significantly contributing to the water scarcity in these regions. In addition,
      many highly developed but water scarce regions, such as Shanghai, Beijing, and
      Tianjin, are already large importers of net virtual water at the expense of water
      resource depletion in other water scarce provinces. Thus, increasingly importing
      water-intensive goods from other water-scarce regions may just shift the pressure
      to other regions, but the overall water problems may still remain. Using the
      water footprint as a policy tool to alleviate water shortage may only work when
      water scarcity is taken into account and virtual water flows from water-poor
      regions are identified. 

PMID- 24922281
TI  - An HMM-based comparative genomic framework for detecting introgression in
      eukaryotes.
AB  - One outcome of interspecific hybridization and subsequent effects of evolutionary
      forces is introgression, which is the integration of genetic material from one
      species into the genome of an individual in another species. The evolution of
      several groups of eukaryotic species has involved hybridization, and cases of
      adaptation through introgression have been already established. In this work, we
      report on PhyloNet-HMM-a new comparative genomic framework for detecting
      introgression in genomes. PhyloNet-HMM combines phylogenetic networks with hidden
      Markov models (HMMs) to simultaneously capture the (potentially reticulate)
      evolutionary history of the genomes and dependencies within genomes. A novel
      aspect of our work is that it also accounts for incomplete lineage sorting and
      dependence across loci. Application of our model to variation data from
      chromosome 7 in the mouse (Mus musculus domesticus) genome detected a recently
      reported adaptive introgression event involving the rodent poison resistance gene
      Vkorc1, in addition to other newly detected introgressed genomic regions. Based
      on our analysis, it is estimated that about 9% of all sites within chromosome 7
      are of introgressive origin (these cover about 13 Mbp of chromosome 7, and over
      300 genes). Further, our model detected no introgression in a negative control
      data set. We also found that our model accurately detected introgression and
      other evolutionary processes from synthetic data sets simulated under the
      coalescent model with recombination, isolation, and migration. Our work provides
      a powerful framework for systematic analysis of introgression while
      simultaneously accounting for dependence across sites, point mutations,
      recombination, and ancestral polymorphism. 

PMID- 24922284
TI  - The haemophilia certification system in Canada.

PMID- 24922285
TI  - The national haemophilia program standards, evaluation and oversight systems in
      the United States of America.

PMID- 24922286
TI  - Haemophilia Centre Certification Systems: optional or optimal choice for
      healthcare systems?

PMID- 24922287
TI  - Haemophilia Centre certification system across Europe: the Belgian experience.

PMID- 24922288
TI  - Quality of haemophilia care in The Netherlands: new standards for optimal care.
AB  - BACKGROUND: In the Netherlands, the first formal haemophilia comprehensive care
      centre was established in 1964, and Dutch haemophilia doctors have been organised
      since 1972. Although several steps were taken to centralise haemophilia care and
      maintain quality of care, treatment was still delivered in many hospitals, and
      formal criteria for haemophilia treatment centres as well as a national
      haemophilia registry were lacking. MATERIAL AND METHODS: In collaboration with
      patients and other stakeholders, Dutch haemophilia doctors have undertaken a
      formal process to draft new quality standards for the haemophilia treatment
      centres. First a project group including doctors, nurses, patients and the
      institute for harmonisation of quality standards undertook a literature study on
      quality standards and performed explorative visits to several haemophilia
      treatment centres in the Netherlands. Afterwards concept standards were defined
      and validated in two treatment centres. Next, the concept standards were
      evaluated by haemophilia doctors, patients, health insurance representatives and
      regulators. Finally, the final version of the standards of care was approved by
      Central body of Experts on quality standards in clinical care and the Dutch
      Ministry of Health. RESULTS: A team of expert auditors have been trained and,
      together with an independent auditor, will perform audits in haemophilia centres
      applying for formal certification. Concomitantly, a national registry for
      haemophilia and allied disorders is being set up. DISCUSSION: It is expected that
      these processes will lead to further concentration and improved quality of
      haemophilia care in the Netherlands.

PMID- 24922289
TI  - A certification/accreditation model for Haemophilia Centres in Italy.
AB  - BACKGROUND: The Italian Association of Haemophilia Centres has developed a
      voluntary programme of professional accreditation of Haemophilia Centres, run by
      its members. Participation in the programme, which aims to foster staff
      involvement in clinical governance, includes both medical personnel and nurses.
      MATERIALS AND METHODS: Accreditation is awarded provided the candidate
      Haemophilia Centre is able to adhere to a pre-established set of quality
      standards and meet a number of clinical and organisational requirements,
      previously defined on the basis of evidence-based medicine. Self-evaluation is
      the first step in the programme, followed by a site visit by a team of peer
      professionals experienced in quality auditing. RESULTS: The programme has so far
      involved 21 Italian Haemophilia Centres. The comparison between self- and peer
      evaluation revealed less discrepancies for disease-related than for
      organisational requirements, the latter being met to a lesser degree by most
      Haemophilia Centres. DISCUSSION: This programme of professional accreditation
      developed by the Italian Association of Haemophilia Centres has the potential to
      describe, monitor and improve clinical and organisational performances in the
      management of patients with haemophilia and allied inherited coagulation
      disorders. It should also be seen as a contribution to the implementation of the
      strategy for improving professional governance in Haemophilia Centres.

PMID- 24922290
TI  - The Italian institutional accreditation model for Haemophilia Centres.
AB  - BACKGROUND: In Italy, basic health needs of patients with inherited bleeding
      disorders are met by a network of 50 haemophilia centres belonging to the Italian
      Association of Haemophilia Centres. Further emerging needs, due to the increased
      life expectancy of this patient group, require a multi-professional clinical
      management of the disease and provide a challenge to the organisation of
      centres.In order to achieve harmonised quality standards of haemophilia care
      across Italian Regions, an institutional accreditation model for haemophilia
      centres has been developed. MATERIAL AND METHODS: To develop an accreditation
      scheme for haemophilia centres, a panel of experts representing medical and
      patient bodies, the Ministry of Health and Regional Health Authorities has been
      appointed by the National Blood Centre. Following a public consultation, a
      technical proposal in the form of recommendations for Regional Health Authorities
      has been formally submitted to the Ministry of Health and has formed the basis
      for a proposal of Agreement between the Government and the Regions. RESULTS: The
      institutional accreditation model for Haemophilia Centres was approved as an
      Agreement between the Government and the Regions in March 2013. It identified 23
      organisational requirements for haemophilia centres covering different areas and
      activities. DISCUSSION: The Italian institutional accreditation model aims to
      achieve harmonised quality standards across Regions and to implement continuous
      improvement efforts, certified by regional inspection systems. The identified
      requirements are considered as necessary and appropriate in order to provide
      haemophilia services as "basic healthcare levels" under the umbrella of the
      National Health Service. This model provides Regions with a flexible
      institutional accreditation scheme that can be potentially extended to other rare
      diseases.

PMID- 24922291
TI  - The European Haemophilia Network (EUHANET).

PMID- 24922292
TI  - The methodology for defining the European standards for the certification of
      Haemophilia Centres in Europe.
AB  - INTRODUCTION: Work Package 4 Development of the standardisation criteria of the
      European Haemophilia Network project has the main objective of implementing a
      common and shared European strategy for a certification system for two levels of
      Haemophilia Centres: European Haemophilia Treatment Centres and European
      Haemophilia Comprehensive Care Centres in the Member States of the European
      Union. MATERIALS AND METHODS: An inclusive and participatory process for
      developing shared standards and criteria for the management of patients with
      inherited bleeding disorders has been carried out. The process has been
      implemented through four different consultation events involving the entire
      European community of stakeholders that significantly contributed in the drafting
      of the European Guidelines for the certification of Haemophilia Centres. RESULTS:
      The Guidelines set the standards for the designation of centres that provide
      specialised and multidisciplinary care (Haemophilia Comprehensive Care Centres)
      as well as local routine care (Haemophilia Treatment Centres). Standards cover
      several issues such as: general requirements; patient care; advisory services;
      laboratory; networking of clinical and specialised services. CONCLUSIONS: The
      drafting of the European Guidelines for the certification of Haemophilia Centres
      was performed adopting a rigorous methodological approach. In order to build the
      widest possible consensus to the quality standards, the main institutional and
      scientific stakeholders have been involved. The resulting document will
      significantly contribute in promoting standardisation in the quality of diagnosis
      and treatment in European Haemophilia Centres.

PMID- 24922293
TI  - The European standards of Haemophilia Centres.
AB  - INTRODUCTION: The European haemophilia community of professionals and patients
      has agreed on the principles of haemophilia care to address comprehensive optimal
      delivery of care which is nowadays scattered throughout Europe. Many of the
      health facilities call themselves Haemophilia Centres despite their variation in
      size, expertise and services provided. Only a small number of countries have
      Haemophilia Centre accreditation systems in place. METHODS: In the framework of
      the European Haemophilia Network project, following an inclusive process of
      stakeholder involvement, the European Guidelines for the certification of
      haemophilia centres have been developed in order to set quality standards for
      European Haemophilia Centres and criteria for their certification. RESULTS: The
      Guidelines define the standards and criteria for the designation of two levels of
      care delivery: European Haemophilia Treatment Centres, providing local routine
      care, and European Haemophilia Comprehensive Care Centres, providing specialised
      and multi-disciplinary care and functioning as tertiary referral centres.
      Additionally, they define standards about general requirements, patient care,
      provision of an advisory service and establishment of network of clinical and
      specialised services. CONCLUSIONS: The implementation of the European Guidelines
      for the certification of Haemophilia Centres will contribute to the reduction of
      health inequalities through the standardisation of quality of care in European
      Union Member States and could represent a model to be taken into consideration
      for other rare disease groups.

PMID- 24922294
TI  - Institutional accreditation of Health Services in Italy: the long road to
      quality.

PMID- 24922295
TI  - Current and evolving features in the clinical management of haemophilia.

PMID- 24922296
TI  - Uncovered needs in the management of inherited bleeding disorders in Italy.

PMID- 24922297
TI  - The social burden and quality of life of patients with haemophilia in Italy.
AB  - BACKGROUND: In Italy, the project on the social burden and quality of life (QoL)
      of patients with haemophilia investigates costs from a society perspective and
      provides an overview of their quality of life. Moreover, as life expectancy
      increased in recent years along with new treatment strategies implemented in the
      last decades, it analyses trends of costs other than drugs simulating impacts
      during patient whole life. MATERIAL AND METHODS: We ran a web-based cross
      sectional survey supported by the Italian Federation of Haemophilia Societies in
      recruiting patients with haemophilia and their caregivers. We developed a
      questionnaire to collect information on demographic characteristics, healthcare
      and social services consumption, formal and informal care utilisation,
      productivity loss and quality of life. In particular, quality of life was
      assessed through the EuroQoL tool. Last, we applied the illness cost method from
      a society perspective. RESULTS: On average, quality of life is worse in adult
      patients compared to child and caregivers: more than 75% of adult patients
      declare physical problems, 43% of adult patients and 54% of their parents have
      anxiety problems. Assuming a society perspective, the estimated mean annual total
      cost per patient in 2012 is 117,732 ?. Drugs represent 92% of total costs.
      Focusing on costs other than drugs, each additional point of EuroQoL tool implies
      a costs' reduction of 279 ?. The impact of age varies across age groups: each
      added year implies a total decrease of costs up to 46.6 years old. Afterwards,
      every additional year increases costs. DISCUSSION: Quality of life of patients
      with haemophilia and their caregivers improved and it influences positively on
      consumed resources and on their contribution to the social-economic system. Costs
      other than drugs for patients with haemophilia follow the same trends of general
      population.

PMID- 24922298
TI  - Current status of Italian Registries on inherited bleeding disorders.

PMID- 24922299
TI  - Definition of an organisational model for the prevention and reduction of health
      and social impacts of inherited bleeding disorders.
AB  - INTRODUCTION: Due to the increase in life expectancy, patients with haemophilia
      and other inherited bleeding disorders are experiencing age-related comorbidities
      that present new challenges. In order to meet current and emerging needs, a model
      for healthcare pathways was developed through a project funded by the Italian
      Ministry of Health. The project aimed to prevent or reduce the social-health
      burden of the disease and its complications. MATERIAL AND METHODS: The National
      Blood Centre appointed a panel of experts comprising clinicians, patients,
      National and Regional Health Authority representatives. Following an analysis of
      the scientific and regulatory references, the panel drafted a technical proposal
      containing recommendations for Regional Health Authorities, which has been
      formally submitted to the Ministry of Health. Finally, a set of indicators to
      monitor haemophilia care provision has been defined. RESULTS: In the technical
      document, the panel of experts proposed the adoption of health policy
      recommendations summarised in areas, such as: multidisciplinary integrated
      approach for optimal healthcare provision; networking and protocols for emergency
      care; home therapy; registries/databases; replacement therapy supply and
      distribution; recruitment and training of experts in bleeding disorders. The
      recommendations became the content of proposal of agreement between the
      Government and the Regions. Monitoring and evaluation of haemophilia care through
      the set of established indicators was partially performed due to limited
      available data. CONCLUSIONS: The project provided recommendations for the
      clinical and organisational management of patient with haemophilia. A particular
      concern was given to those areas that play a critical role in the comorbidities
      and complications prevention. Recommendations are expected to harmonise
      healthcare care delivery across regional networks and building the foundation for
      the national haemophilia network.

PMID- 24922300
TI  - The Italian National Centre for Rare Diseases: where research and public health
      translate into action.

PMID- 24922301
TI  - The Italian National Rare Diseases Registry.
AB  - INTRODUCTION: Rare disease registries are a priority at European level and
      specific actions are being implemented by the European Commission to support
      their development.In Italy, a National Registry of rare diseases has been
      established in 2001 as a network of regional registries. The latter have
      gradually been established and the full coverage of the Italian territory was
      attained during 2011. METHODS: Here we describe the basic features of the
      National Registry of rare diseases; the activities carried out to promote
      consistent operations in the regional registries; and the overall quality and
      composition of the records collected. RESULTS: After a validation process,
      including removal of duplicate records, 110,841 records of patients with rare
      diseases, single and with group denominations, are stored in the National
      Registry of rare diseases. They correspond to the overall diagnoses communicated
      to national registry by regional registries up to 30 June 2012.The quality of the
      data collected by the the National Registry of rare diseases has been assessed
      with respect to completeness and consistency of procedures. Variables
      characterising case and diagnosis showed a very limited number of missing values.
      Records reported at least one case of 485 rare conditions. DISCUSSION: To date,
      the National Registry of rare diseases is a surveillance system with the main
      objective of producing epidemiologic evidence on rare diseases in Italy, and of
      supporting policy making and health services planning.Data quality still
      represents a limitation for any sound epidemiological estimate of rare diseases
      in Italy. However, improvements of the quality of collected data and the
      completeness of case notifications should be strengthened.

PMID- 24922302
TI  - The Italian National Plan for Rare Diseases.

PMID- 24922303
TI  - Piedmont and Aosta Valley inter-regional network in the context of the Italian
      National Network for rare diseases.

PMID- 24922304
TI  - Centres of Expertise and European Reference Networks: key issues in the field of
      rare diseases. The EUCERD Recommendations.
AB  - BACKGROUND: Rare diseases, because of their intrinsic characteristics - large
      number of disorders and syndromes, low individual prevalence, severity, often
      limited information, lack of therapies - can benefit from collaboration and
      sharing of expertise while maximising the limited resources available for these
      conditions. Therefore, the development of Centres of Expertise (CEs) and European
      Reference Networks (ERNs) in this field is crucial.The European Union Committee
      of Experts on Rare Diseases (EUCERD) has been charged to assist the European
      Commission with the preparation and implementation of activities in the field of
      rare diseases in Europe. In particular, EUCERD has assisted the EC in drawing up
      the recommendations issued in the Commission Communication and in the Council
      Recommendation. In this paper the authors focus on the EUCERD Recommendations on
      CEs and one on ERNs. MATERIALS AND METHODS: Recommendations on CEs and ERNs are
      the result of two different processes, developed through iterative reviews and
      discussions at workshops and EUCERD meetings, and according to the European Union
      documents. RESULTS: EUCERD has issued two complementary Recommendations, one on
      CEs (2011) and a second on ERNs (2013). Both address multiple targets (from
      Member States to Centres, and patient organisations), with the objective of
      helping them define and organise CEs and ERNs. CONCLUSIONS: The establishment,
      designation, financial support, and evaluation of CEs throughout Europe allow RD
      patients and local health care providers to identify high-quality specialised
      services that can simplify disease management and improve patients' care. The
      EUCERD Recommendations are useful instruments to help and guide stakeholders in
      the development of CEs and ERNs and thus ensure equity of access to services and
      care for rare diseases patients across Europe.

PMID- 24922305
TI  - European Reference Networks for Rare Diseases: the vision of patients.

PMID- 24922307
TI  - Pharmacogenomics of human uridine diphospho-glucuronosyltransferases and clinical
      implications.
AB  - Glucuronidation by uridine diphospho-glucuronosyltransferase enzymes (UGTs) is a
      major phase II biotransformation pathway and, complementary to phase I metabolism
      and membrane transport, one of the most important cellular defense mechanisms
      responsible for the inactivation of therapeutic drugs, other xenobiotics, and
      endogenous molecules. Interindividual variability in UGT pathways is significant
      and may have profound pharmacological and toxicological implications. Several
      genetic and genomic processes underlie this variability and are discussed in
      relation to drug metabolism and diseases such as cancer. 

PMID- 24922306
TI  - The HY5-PIF regulatory module coordinates light and temperature control of
      photosynthetic gene transcription.
AB  - The ability to interpret daily and seasonal alterations in light and temperature
      signals is essential for plant survival. This is particularly important during
      seedling establishment when the phytochrome photoreceptors activate
      photosynthetic pigment production for photoautotrophic growth. Phytochromes
      accomplish this partly through the suppression of phytochrome interacting factors
      (PIFs), negative regulators of chlorophyll and carotenoid biosynthesis. While the
      bZIP transcription factor long hypocotyl 5 (HY5), a potent PIF antagonist,
      promotes photosynthetic pigment accumulation in response to light. Here we
      demonstrate that by directly targeting a common promoter cis-element (G-box), HY5
      and PIFs form a dynamic activation-suppression transcriptional module responsive
      to light and temperature cues. This antagonistic regulatory module provides a
      simple, direct mechanism through which environmental change can redirect
      transcriptional control of genes required for photosynthesis and photoprotection.
      In the regulation of photopigment biosynthesis genes, HY5 and PIFs do not operate
      alone, but with the circadian clock. However, sudden changes in light or
      temperature conditions can trigger changes in HY5 and PIFs abundance that adjust
      the expression of common target genes to optimise photosynthetic performance and
      growth.

PMID- 24922308
TI  - Comparative pathogenesis of Alkhumra hemorrhagic fever and Kyasanur forest
      disease viruses in a mouse model.
AB  - Kyasanur Forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (AHFV)
      are genetically closely-related, tick-borne flaviviruses that cause severe, often
      fatal disease in humans. Flaviviruses in the tick-borne encephalitis (TBE)
      complex typically cause neurological disease in humans whereas patients infected
      with KFDV and AHFV predominately present with hemorrhagic fever. A small animal
      model for KFDV and AHFV to study the pathogenesis and evaluate countermeasures
      has been lacking mostly due to the need of a high biocontainment laboratory to
      work with the viruses. To evaluate the utility of an existing mouse model for
      tick-borne flavivirus pathogenesis, we performed serial sacrifice studies in
      BALB/c mice infected with either KFDV strain P9605 or AHFV strain Zaki-1.
      Strikingly, infection with KFDV was completely lethal in mice, while AHFV caused
      no clinical signs of disease and no animals succumbed to infection. KFDV and high
      levels of pro-inflammatory cytokines were detected in the brain at later time
      points, but no virus was found in visceral organs; conversely, AHFV Zaki-1 and
      elevated levels of cytokines were found in the visceral organs at earlier time
      points, but were not detected in the brain. While infection with either virus
      caused a generalized leukopenia, only AHFV Zaki-1 induced hematologic
      abnormalities in infected animals. Our data suggest that KFDV P9605 may have lost
      its ability to cause hemorrhagic disease as the result of multiple passages in
      suckling mouse brains. However, likely by virtue of fewer mouse passages, AHFV
      Zaki-1 has retained the ability to replicate in visceral organs, cause
      hematologic abnormalities, and induce pro-inflammatory cytokines without causing
      overt disease. Given these striking differences, the use of inbred mice and the
      virus passage history need to be carefully considered in the interpretation of
      animal studies using these viruses. 

PMID- 24922309
TI  - Validation of the Pangao PG-800B5 for clinical use and self-measurement according
      to the European Society of Hypertension International Protocol revision 2010.
AB  - OBJECTIVES: This study aimed to validate the Pangao PG-800B5 upper arm blood
      pressure monitor according to the European Society of Hypertension International
      Protocol revision 2010. METHODS: A total of 33 participants, 16 men and 17 women,
      were included in the device evaluation. The protocol requirements were followed
      precisely. RESULTS: The mean age of the participants was 56.4+/-21.0 years (range
      22-84 years). The mean systolic blood pressure was 143.6+/-25.5 mmHg (range 98
      188 mmHg), the mean diastolic blood pressure was 85.7+/-17.2 mmHg (range 49-125
      mmHg), and the mean arm circumference was 26.1+/-2.2 cm (range 23-32 cm). On
      average, the device overestimated the systolic blood pressure by 0.9+/-4.2 mmHg
      and diastolic blood pressure by 0.7+/-4.5 mmHg. CONCLUSIONS: The device passed
      all requirements, fulfilling the standards of the protocol. Therefore, the Pangao
      PG-800B5 upper arm blood pressure monitor can be recommended for clinical use and
      self-measurement in an adult population.

PMID- 24922310
TI  - CGBayesNets: conditional Gaussian Bayesian network learning and inference with
      mixed discrete and continuous data.
AB  - Bayesian Networks (BN) have been a popular predictive modeling formalism in
      bioinformatics, but their application in modern genomics has been slowed by an
      inability to cleanly handle domains with mixed discrete and continuous variables.
      Existing free BN software packages either discretize continuous variables, which
      can lead to information loss, or do not include inference routines, which makes
      prediction with the BN impossible. We present CGBayesNets, a BN package focused
      around prediction of a clinical phenotype from mixed discrete and continuous
      variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and
      inference algorithms for the conditional Gaussian Bayesian network (CGBNs)
      formalism, one appropriate for predicting an outcome of interest from, e.g.,
      multimodal genomic data. We provide four different network learning algorithms,
      each making a different tradeoff between computational cost and network
      likelihood. CGBayesNets provides a full suite of functions for model exploration
      and verification, including cross validation, bootstrapping, and AUC
      manipulation. We highlight several results obtained previously with CGBayesNets,
      including predictive models of wood properties from tree genomics, leukemia
      subtype classification from mixed genomic data, and robust prediction of
      intensive care unit mortality outcomes from metabolomic profiles. We also provide
      detailed example analysis on public metabolomic and gene expression datasets.
      CGBayesNets is implemented in MATLAB and available as MATLAB source code, under
      an Open Source license and anonymous download at http://www.cgbayesnets.com. 

PMID- 24922311
TI  - Crisis of Japanese vascular flora shown by quantifying extinction risks for 1618
      taxa.
AB  - Although many people have expressed alarm that we are witnessing a mass
      extinction, few projections have been quantified, owing to limited availability
      of time-series data on threatened organisms, especially plants. To quantify the
      risk of extinction, we need to monitor changes in population size over time for
      as many species as possible. Here, we present the world's first quantitative
      projection of plant species loss at a national level, with stochastic simulations
      based on the results of population censuses of 1618 threatened plant taxa in 3574
      map cells of ca. 100 km2. More than 500 lay botanists helped monitor those taxa
      in 1994-1995 and in 2003-2004. We projected that between 370 and 561 vascular
      plant taxa will go extinct in Japan during the next century if past trends of
      population decline continue. This extinction rate is approximately two to three
      times the global rate. Using time-series data, we show that existing national
      protected areas (PAs) covering ca. 7% of Japan will not adequately prevent
      population declines: even core PAs can protect at best <60% of local populations
      from decline. Thus, the Aichi Biodiversity Target to expand PAs to 17% of land
      (and inland water) areas, as committed to by many national governments, is not
      enough: only 29.2% of currently threatened species will become non-threatened
      under the assumption that probability of protection success by PAs is 0.5, which
      our assessment shows is realistic. In countries where volunteers can be organized
      to monitor threatened taxa, censuses using our method should be able to quantify
      how fast we are losing species and to assess how effective current conservation
      measures such as PAs are in preventing species extinction. 

PMID- 24922312
TI  - Depression in primary care patients with coronary heart disease: baseline
      findings from the UPBEAT UK study.
AB  - BACKGROUND: An association between depression and coronary heart disease is now
      accepted but there has been little primary care research on this topic. The
      UPBEAT-UK studies are centred on a cohort of primary patients with coronary heart
      disease assessed every six months for up to four years. The aim of this research
      was to determine the prevalence and associations of depression in this cohort at
      baseline. METHOD: Participants with coronary heart disease were recruited from
      general practice registers and assessed for cardiac symptoms, depression, quality
      of life and social problems. RESULTS: 803 people participated. 42% had a
      documented history of myocardial infarction, 54% a diagnosis of ischaemic heart
      disease or angina. 44% still experienced chest pain. 7% had an ICD-10 defined
      depressive disorder. Factors independently associated with this diagnosis were
      problems living alone (OR 5.49, 95% CI 2.11-13.30), problems carrying out usual
      activities (OR 3.71, 95% CI 1.93-7.14), experiencing chest pain (OR 3.27, 95% CI
      1.58-6.76), other pains or discomfort (OR 3.39, 95% CI 1.42-8.10), younger age
      (OR 0.95 per year 95% CI 0.92-0.98). CONCLUSION: Problems living alone, chest
      pain and disability are important predictors of depression in this population.

PMID- 24922314
TI  - 9(th) International Forum on Mood and Anxiety Disorders.

PMID- 24922315
TI  - 9(th) International Forum on Mood and Anxiety Disorders.

PMID- 24922316
TI  - 9(th) International Forum on Mood and Anxiety Disorders.

PMID- 24922313
TI  - Opposing effects of alpha2- and beta-adrenergic receptor stimulation on quiescent
      neural precursor cell activity and adult hippocampal neurogenesis.
AB  - Norepinephrine regulates latent neural stem cell activity and adult hippocampal
      neurogenesis, and has an important role in modulating hippocampal functions such
      as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage
      process, spanning from the activation and proliferation of hippocampal stem
      cells, to their differentiation into neurons. However, the stage-specific effects
      of noradrenergic receptors in regulating adult hippocampal neurogenesis remain
      poorly understood. In this study, we used transgenic Nestin-GFP mice and
      neurosphere assays to show that modulation of alpha2- and beta-adrenergic
      receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell
      population albeit in an opposing fashion. While selective stimulation of alpha2
      adrenergic receptors decreases precursor cell activation, proliferation and
      immature neuron number, stimulation of beta-adrenergic receptors activates the
      quiescent precursor pool and enhances their proliferation in the adult
      hippocampus. Furthermore, our data indicate no major role for alpha1-adrenergic
      receptors, as we did not observe any change in either the activation and
      proliferation of hippocampal precursors following selective stimulation or
      blockade of alpha1-adrenergic receptors. Taken together, our data suggest that
      under physiological as well as under conditions that lead to enhanced
      norepinephrine release, the balance between alpha2- and beta-adrenergic receptor
      activity regulates precursor cell activity and hippocampal neurogenesis. 

PMID- 24922317
TI  - The role of abiotic environmental conditions and herbivory in shaping bacterial
      community composition in floral nectar.
AB  - Identifying the processes that drive community assembly has long been a central
      theme in ecology. For microorganisms, a traditional prevailing hypothesis states
      that "everything is everywhere, but the environment selects". Although the
      bacterial community in floral nectar may be affected by both atmosphere (air
      borne bacteria) and animals as dispersal vectors, the environmental and
      geographic factors that shape microbial communities in floral nectar are unknown.
      We studied culturable bacterial communities in Asphodelus aestivus floral nectar
      and in its typical herbivorous bug Capsodes infuscatus, along an aridity
      gradient. Bacteria were sampled from floral nectar and bugs at four sites,
      spanning a geographical range of 200 km from Mediterranean to semi-arid
      conditions, under open and bagged flower treatments. In agreement with the niche
      assembly hypothesis, the differences in bacterial community compositions were
      explained by differences in abiotic environmental conditions. These results
      suggest that microbial model systems are useful for addressing macro-ecological
      questions. In addition, similar bacterial communities were found in the nectar
      and on the surface of the bugs that were documented visiting the flowers. These
      similarities imply that floral nectar bacteria dispersal is shaped not only by
      air borne bacteria and nectar consumers as previously reported, but also by
      visiting vectors like the mirid bugs. 

PMID- 24922318
TI  - Palladium(II)/Lewis acid synergistically catalyzed allylic C-H olefination.
AB  - The first allylic C-H olefination with alpha-diazo esters synergistically
      catalyzed by a palladium(II) complex and (salen)CrCl has been established to
      directly generate conjugated polyene derivatives in moderate to high yields and
      with excellent stereoselectivities. 

PMID- 24922319
TI  - Inhibition of PAI-1 antiproteolytic activity against tPA by RNA aptamers.
AB  - Plasminogen activator inhibitor-1 (PAI-1; SERPINE1) inhibits the plasminogen
      activators: tissue-type plasminogen activator (tPA) and urokinase-type
      plasminogen activator (uPA). Elevated levels of PAI-1 have been correlated with
      an increased risk for cardiovascular disease. Pharmacologically suppressing PAI-1
      might prevent, or successfully treat PAI-1 related vascular diseases. This can
      potentially be accomplished by using small RNA molecules (aptamers). This study's
      goal is to develop RNA aptamers to a region of PAI-1 that will prevent the
      ability of PAI-1 to interact with the plasminogen activators. The aptamers were
      generated through a systematic evolution of ligands via exponential enrichment
      approach that ensures the creation of RNA molecules that bind to our target
      protein, PAI-1. In vitro assays were used to determine the effect of these
      aptamers on PAI-1's inhibitory activity. Three aptamers that bind to PAI-1 with
      affinities in the nanomolar range were isolated. The aptamer clones R10-4 and R10
      2 inhibited PAI-1's antiproteolytic activity against tPA and disrupted PAI-1's
      ability to form a stable covalent complex with tPA. Increasing aptamer
      concentrations correlated positively with an increase in cleaved PAI-1. To the
      best of our knowledge, this is the first report of RNA molecules that inhibit the
      antiproteolytic activity of PAI-1. 

PMID- 24922320
TI  - Discovering functional modules across diverse maize transcriptomes using COB, the
      Co-expression Browser.
AB  - Tools that provide improved ability to relate genotype to phenotype have the
      potential to accelerate breeding for desired traits and to improve our
      understanding of the molecular variants that underlie phenotypes. The
      availability of large-scale gene expression profiles in maize provides an
      opportunity to advance our understanding of complex traits in this agronomically
      important species. We built co-expression networks based on genome-wide
      expression data from a variety of maize accessions as well as an atlas of
      different tissues and developmental stages. We demonstrate that these networks
      reveal clusters of genes that are enriched for known biological function and
      contain extensive structure which has yet to be characterized. Furthermore, we
      found that co-expression networks derived from developmental or tissue atlases as
      compared to expression variation across diverse accessions capture unique
      functions. To provide convenient access to these networks, we developed a public,
      web-based Co-expression Browser (COB), which enables interactive queries of the
      genome-wide networks. We illustrate the utility of this system through two
      specific use cases: one in which gene-centric queries are used to provide
      functional context for previously characterized metabolic pathways, and a second
      where lists of genes produced by mapping studies are further resolved and
      validated using co-expression networks. 

PMID- 24922321
TI  - Combined spinal epidural analgesia for labor using sufentanil epidurally versus
      intrathecally: a retrospective study on the influence on fetal heart trace.
AB  - OBJECTIVE: We retrospectively compared a protocol using sufentanil and
      ropivacaine intrathecally with a protocol in which only ropivacaine was
      administered intrathecally and sufentanil was used epidurally to evaluate whether
      banning sufentanil from the intrathecal space results in a decreased incidence of
      adverse fetal heart rate changes. METHODS: Some 520 cardiotocographic tracings
      were examined for changes in fetal heart rate and uterine activity following two
      different protocols of combined spinal epidural analgesia. Charts were consulted
      for neonatal and labor outcome. RESULTS: When sufentanil was used epidurally
      instead of intrathecally, the incidence of adverse changes in fetal heart trace
      was less, demonstrated by a higher percentage of normal reassuring tracings
      (74.5% vs. 60.4% when sufentanil was used intrathecally; P=0.007), less tracings
      showing bradycardia (7.5% vs. 14.1%; P=0.035), and more tracings displaying 3 or
      more accelerations in fetal heart rate in 45 min (93.5% vs. 83.9%; P=0.003)
      together with less episodes of tachycardia (3.5% vs. 11.4%; P=0.005). There were
      no differences in labor and neonatal outcome. CONCLUSIONS: Based on fetal heart
      tracing, it seems favorable to ban sufentanil from the intrathecal compartment.

PMID- 24922322
TI  - Revisiting the coding potential of the E. coli genome through Hfq co
      immunoprecipitation.
AB  - Hfq is a global regulator of gene expression in bacteria undergoing adaptation to
      changing environmental conditions. Its major function is to promote RNA-RNA
      interactions between regulatory small RNAs (sRNAs) and their target mRNAs.
      Previously, we demonstrated that Hfq binds many antisense RNAs (asRNAs) in vitro
      and hypothesized that Hfq may play a role in regulating gene expression via
      asRNAs. To investigate the E. coli Hfq-binding transcriptome in more detail, we
      co-immunoprecipitated and deep-sequenced RNAs bound to Hfq in vivo. We detected
      many new Hfq-binding sRNAs and observed that almost 300 mRNAs bind to Hfq. Among
      these, several are known to be sRNA targets. We identified 25 novel RNAs, which
      are transcribed from within protein coding regions and named them intragenic RNAs
      (intraRNAs). Furthermore, 67 asRNAs were co-immunoprecipitated with Hfq,
      demonstrating that Hfq binds antisense transcripts in vivo. Northern blot
      analyses confirmed the deep-sequencing results and demonstrated that many of the
      novel Hfq-binding RNAs identified are regulated by Hfq. 

PMID- 24922323
TI  - A new method to quantify within dive foraging behaviour in marine predators.
AB  - Studies on diving behaviour classically divide a dive into three phases: the
      descent, bottom and ascent phases, with foraging assumed to occur during the
      bottom phase. The greater complexity of dive revealed through modern, high
      resolution data highlights the need to re-assess this approach and to consider a
      larger number of phases within individual dives. Two southern elephant seals
      (SES) were fitted with a head mounted Time Depth Recorder (TDR) and an
      accelerometer from which prey capture attempts were estimated. A Weddell seal was
      also fitted with a TDR. TDRs for both species recorded depth once per second. We
      quantified the within dive behaviour using an automated broken stick algorithm
      identifying the optimal number of segments within each dive. The vertical
      sinuosity of the segments was used to infer two types of behaviours, with highly
      sinuous segments indicating "hunting" and less sinuous segments indicating
      "transiting". Using the broken stick method the seals alternated between
      "hunting" and "transit" modes with an average of 6+/-2 and 7+/-0.02 behavioural
      phases within each dive for the Weddell seal and SES, respectively. In SES, 77%
      of prey capture attempts (identified from the acceleration data) occurred in
      highly sinuous phases ("hunting") as defined by our new approach. SES spent more
      time in transit mode within a dive, and hunting mostly occurred during the bottom
      phase. Conversely the Weddell seal spent more time in hunting mode which also
      occurred during bottom phase but occurred mostly at shallower depths. Such
      differences probably reflect different foraging tactics and habitat use. For both
      species, hunting time differs significantly from bottom time previously used as a
      proxy for the time spent foraging in a dive. The hunting time defined by our
      method therefore provides a more accurate fine-scale description of the seals'
      foraging behaviour. 

PMID- 24922324
TI  - Annotation of long non-coding RNAs expressed in collaborative cross founder mice
      in response to respiratory virus infection reveals a new class of interferon
      stimulated transcripts.
AB  - The outcome of respiratory virus infection is determined by a complex interplay
      of viral and host factors. Some potentially important host factors for the
      antiviral response, whose functions remain largely unexplored, are long non
      coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions
      of host lncRNAs in response to influenza A virus and severe acute respiratory
      syndrome coronavirus (SARS-CoV) based on their similarity in expression with
      genes of known function. We performed total RNA-Seq on viral-infected lungs from
      eight mouse strains, yielding a large data set of transcriptional responses.
      Overall 5,329 lncRNAs were differentially expressed after infection. Most of the
      lncRNAs were co-expressed with coding genes in modules enriched in genes
      associated with lung homeostasis pathways or immune response processes. Each
      lncRNA was further individually annotated using a rank-based method, enabling us
      to associate 5,295 lncRNAs to at least one gene set and to predict their
      potential cis effects. We validated the lncRNAs predicted to be interferon
      stimulated by profiling mouse responses after interferon-alpha treatment.
      Altogether, these results provide a broad categorization of potential lncRNA
      functions and identify subsets of lncRNAs with likely key roles in respiratory
      virus pathogenesis. These data are fully accessible through the MOuse NOn-Code
      Lung interactive database (MONOCLdb). 

PMID- 24922325
TI  - Multiparametric MRI characterization and prediction in autism spectrum disorder
      using graph theory and machine learning.
AB  - This study employed graph theory and machine learning analysis of multiparametric
      MRI data to improve characterization and prediction in autism spectrum disorders
      (ASD). Data from 127 children with ASD (13.5+/-6.0 years) and 153 age- and gender
      matched typically developing children (14.5+/-5.7 years) were selected from the
      multi-center Functional Connectome Project. Regional gray matter volume and
      cortical thickness increased, whereas white matter volume decreased in ASD
      compared to controls. Small-world network analysis of quantitative MRI data
      demonstrated decreased global efficiency based on gray matter cortical thickness
      but not with functional connectivity MRI (fcMRI) or volumetry. An integrative
      model of 22 quantitative imaging features was used for classification and
      prediction of phenotypic features that included the autism diagnostic observation
      schedule, the revised autism diagnostic interview, and intelligence quotient
      scores. Among the 22 imaging features, four (caudate volume, caudate-cortical
      functional connectivity and inferior frontal gyrus functional connectivity) were
      found to be highly informative, markedly improving classification and prediction
      accuracy when compared with the single imaging features. This approach could
      potentially serve as a biomarker in prognosis, diagnosis, and monitoring disease
      progression. 

PMID- 24922328
TI  - Anatomic double-bundle reconstruction with free tendon graft for chronic ulnar
      instability of the thumb metacarpophalangeal joint.
AB  - Failed primary treatment of thumb metacarpophalangeal ligament injuries may lead
      to chronic instability. Different treatments have been described such as
      secondary ligament suture, fusion, dynamic or static procedures. Techniques to
      restrain the joint stability with various grafts of different configurations have
      been published, but most of these address only the proper collateral ligament.
      Experimental data revealed the importance of the accessory collateral ligament in
      stabilizing the metacarpophalangeal joint. In a former, true anatomic ligament
      reconstruction a bone-tendon graft was used; the tendon was split longitudinally
      to reconstruct both parts of the collateral ligament. This technique was modified
      by the author: a resorbable interference screw was used to fix a free tendon
      graft double in the metacarpal head, creating 2 identical bundles for
      reconstruction of both the proper and the accessory collateral ligament. The
      results of the first 10 patients with chronic ulnar instability in their
      otherwise intact thumb are reported. The mean follow-up was 15 months. Eight
      patients had excellent result and 2 patients had good result according to the
      Glickel grading system. The mean loss of motion in the metacarpophalengeal joint
      was 9% and the mean loss of pinch strength was 9% compared with the contralateral
      thumb. The technical details, pitfalls, complications, and rehabilitation are
      described in this paper. 

PMID- 24922327
TI  - Stereoscopic analysis of optic nerve head parameters in primary open angle
      glaucoma: the glaucoma stereo analysis study.
AB  - PURPOSE: The Glaucoma Stereo Analysis Study (GSAS), a cross sectional multicenter
      collaborative study, used a stereo fundus camera to assess various morphological
      parameters of the optic nerve head (ONH) in glaucoma patients and investigated
      the relationships between these parameters and patient characteristics. SUBJECTS
      AND METHODS: The study included 187 eyes of 187 subjects with primary open angle
      glaucoma or normal tension glaucoma (male: female  = 100: 87, age  = 61+/-9
      years). Stereo pairs of ONH photographs were made with a stereo fundus camera
      (nonmyd WX). ONH morphological parameters were calculated with prototype analysis
      software. In addition to 35 standard parameters, we defined three novel
      parameters: disc tilt angle, rim decentering, and the absolute value of rim
      decentering. The correlation between each parameter and patient characteristics
      was analyzed with Spearman's rank correlation coefficient. RESULTS: Patient
      characteristics included refractive error of -3.38+/-3.75 diopters, intraocular
      pressure (IOP) of 13.6+/-2.6 mmHg, and visual field mean deviation (MD) of 
      4.71+/-3.26 dB. Representative ONH parameters included a horizontal disc width of
      1.66+/-0.28 mm, vertical disc width of 1.86+/-0.23 mm, disc area of 2.42+/-0.63
      mm2, cup area of 1.45+/-0.57 mm2, and cup volume of 0.31+/-0.22 mm3. Correlation
      analysis revealed significant negative associations between vertical cup-to-disc
      ratio (0.82+/-0.08) and MD (r = -0.40, P<0.01) and between disc tilt angle
      (10.5+/-12.5 degrees) and refractive error (r = -0.36, P<0.01). Seventy-five
      percent of the eyes had a positive value for rim decentering (0.30+/-0.42),
      indicating that rim thinning manifested more often as an inferior lesion than a
      superior lesion. CONCLUSION: We used stereoscopic analysis to establish a
      database of ONH parameters, which may facilitate future studies of glaucomatous
      changes in ONH morphology.

PMID- 24922326
TI  - Temporal trends in the Swedish HIV-1 epidemic: increase in non-B subtypes and
      recombinant forms over three decades.
AB  - BACKGROUND: HIV-1 subtype B (HIV-1B) still dominates in resource-rich countries
      but increased migration contributes to changes in the global subtype
      distribution. Also, spread of non-B subtypes within such countries occurs. The
      trend of the subtype distribution from the beginning of the epidemic in the
      country has earlier not been reported in detail. Thus the primary objective of
      this study is to describe the temporal trend of the subtype distribution from the
      beginning of the HIV-1 epidemic in Sweden over three decades. METHODS: HIV-1 pol
      sequences from patients (n = 3967) diagnosed in Sweden 1983-2012, corresponding
      to >40% of patients ever diagnosed, were re-subtyped using several automated
      bioinformatics tools. The temporal trends of subtypes and recombinants during
      three decades were described by a multinomial logistic regression model. RESULTS:
      All eleven group M HIV-1 subtypes and sub-subtypes (78%), 17 circulating
      recombinant forms (CRFs) (19%) and 32 unique recombinants forms (URF) (3%) were
      identified. When all patients were analysed, there was an increase of newly
      diagnosed HIV-1C (RR, 95%CI: 1.10, 1.06-1.14), recombinants (1.20, 1.17-1.24) and
      other pure subtypes (1.11, 1.07-1.16) over time compared to HIV-1B. The same
      pattern was found when all patients infected in Sweden (n = 1165) were analysed.
      Also, for MSM patients infected in Sweden (n = 921), recombinant forms and other
      pure subtypes increased. SIGNIFICANCE: Sweden exhibits one of the most diverse
      subtype epidemics outside Africa. The increase of non-B subtypes is due to
      migration and to a spread among heterosexually infected patients and MSM within
      the country. This viral heterogeneity may become a hotspot for development of
      more diverse and complex recombinant forms if the epidemics converge.

PMID- 24922329
TI  - A modified ulnar translocation reconstruction technique for Campanacci grade 3
      giant cell tumors of the distal radius using a clover leaf plate.
AB  - BACKGROUND: Campanacci grade 3 giant cell tumors of the distal radius are locally
      aggressive and in close proximity to the median nerve, articular cartilage,
      flexor and extensor tendons, and the radial artery. Although several
      reconstructive techniques have been described, it is unclear to what degree these
      procedures restore function. DESCRIPTION OF TECHNIQUE: We present a modified
      ipsilateral ulna translocation technique using a clover leaf plate, for
      reconstruction of en bloc resected distal radius. This has the theoretical
      advantage of ensuring a solid, pain-free wrist arthrodesis, while preserving the
      forearm rotational axis and minimizing functional loss, without the associated
      donor site morbidity or allograft rejection issues of other reconstructive
      techniques. PATIENTS AND METHODS: Between 2006 and 2013, 3 patients underwent
      this procedure for Campanacci grade 3 giant cell tumors. All patients were right
      hand-dominant females, aged 24, 35, and 46 years, respectively. Two cases
      involved the right radius. Patients were reviewed retrospectively with clinical
      examination, functional assessment [the Toronto Extremity Salvage Score (TESS)
      for upper limb], and radiographs. The review period was 30, 51, and 41 months,
      respectively. RESULTS: The length of distal radius resected was 70, 50, and 35
      mm, respectively. All achieved clear margins. There were no complications and
      there have been no recurrences. All ulnocarpal translocations achieved
      radiographic fusion. Patient's averaged 80-degree pronation, 70-degree
      supination, and clinical TESS scores of 86 at most recent follow-up. CONCLUSIONS:
      This technique achieved a painless and functional wrist arthrodesis with
      partially restored wrist motion, without complications. This technique has the
      advantage of negating remote donor site morbidity and/or allograft rejection
      issues of other techniques. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 24922330
TI  - Can hospices predict which patients will die within six months?
AB  - OBJECTIVE: To determine whether it is possible to predict, at the time of hospice
      enrollment, which patients will die within 6 months. DESIGN: Electronic health
      record-based retrospective cohort study. SETTING: Patients admitted to 10
      hospices in the CHOICE network (Coalition of Hospices Organized to Investigate
      Comparative Effectiveness). PARTICIPANTS: Hospice patients. MAIN OUTCOME
      MEASURES: Mortality at 6 months following hospice admission. RESULTS: Among
      126,620 patients admitted to 10 hospices, 118,532 (93.6%) died within 6 months.
      In a multivariable logistic regression model, five characteristics were
      independent predictors of 6-month mortality. For instance, patients younger than
      65 years were less likely to die within 6 months (odds ratio [OR] 0.64; 95%
      confidence interval [CI] 0.45-0.91; p=0.014). Conversely, male patients were more
      likely to die within 6 months (OR 1.47; 95% CI 1.05-2.02; p=;0.036). After
      adjusting for other variables in this model, there were several subgroups with a
      low probability of 6-month probability (e.g., stroke and Palliative Performance
      Scale [PPS] score=50; adjusted probability of 6-month mortality=39.4%; 95% CI:
      13.9%-72.5%). However, 95% confidence intervals of these 6-month mortality
      predictions extended above 50%. CONCLUSIONS: Hospices might use several variables
      to identify patients with a relatively low risk for 6-month mortality and who
      therefore may become ineligible to continue hospice services if they fail to show
      significant disease progression.

PMID- 24922331
TI  - Bisphosphonate-induced osteonecrosis of the maxilla presenting as a cicatricial
      ectropion.
AB  - CASE REPORT: A 63-year-old gentleman, who was being treated with bisphosphonates
      for multiple myeloma, presented with a cicatricial ectropion of the lower eyelid,
      without exposure keratopathy. A CT scan demonstrated extensive destruction of
      bone with an infraorbital fracture surrounded by sclerotic bony changes. The
      patient was managed conservatively with discontinuation of bisphosphonate therapy
      and topical ocular lubricants. The patient's condition remained unchanged a year
      after this initial management.

PMID- 24922332
TI  - Co-immobilized poly(ethylene glycol)-block-polyamines promote sensitivity and
      restrict biofouling on gold sensor surface for detecting factor IX in human
      plasma.
AB  - In order to detect an extremely low amount of human coagulation factor IX (FIX),
      poly(ethylene glycol) (PEG)/aptamer co-immobilized surface was constructed using
      original PEG-polyamine surface modification agents on surface plasmon resonance
      (SPR) sensor chip. Initially, a gold (Au) sensor chip of SPR was modified using
      poly(ethylene glycol)-b-poly[2-(N,N-dimethylamino)ethyl methacrylate] (PEG-b
      PAMA) followed by treatment with SH-dT20 and was duplexed with anti-FIX aptamer
      extended using A24. Furthermore, the co-immobilization of pentaethylenehexamine
      terminated poly(ethylene glycol) (N6-PEG) on the sensing surface completely
      quenched bio-fouling. On this dual tethered PEG-surface, we determined that the
      dissociation constant for FIX-aptamer interaction was 37 +/- 10 pM, and the
      sensitivity of detection could reach up to 800 fM on using aptamer-FIX-antibody
      sandwich pattern detected by gold nanoparticle-conjugated anti-mouse antibody. We
      could detect FIX in the presence of abundant albumin. Furthermore, to mimic the
      actual detection of FIX in clinical samples, we demonstrated our experimental
      results with human blood plasma instead of FIX. Higher-sensitivity was attained
      because of dual polymers immobilized on Au surface, and this can emerge as a
      common strategy for any aptamer-protein interactions. The selective binding of
      aptamer in human blood plasma described here indicates the suitability of the
      present strategy for detection in clinically relevant samples. 

PMID- 24922333
TI  - Amino acid misincorporation in recombinant biopharmaceutical products.
AB  - Microbial and mammalian host systems have been used extensively for the
      production of protein biotherapeutics. Generally these systems rely on the
      production of a specific gene sequence encoding one therapeutic product. Analysis
      of these protein products over many years has proven that this was not always the
      case, with multiple species of the intended product being produced due to amino
      acid misincorporation or mistranslation during biosynthesis of the protein. This
      review is the first to give a comprehensive overview of the occurrence and
      analysis of these misincorporations. Furthermore, using the latest data on
      misincorporation in native human proteins we explore potential considerations for
      producing a specification for misincorporation for the development of a human
      biotherapeutic protein product in a production environment. 

PMID- 24922334
TI  - Microbial production of amino acids and derived chemicals: synthetic biology
      approaches to strain development.
AB  - Amino acids are produced at the multi-million-ton-scale with fermentative
      production of l-glutamate and l-lysine alone being estimated to amount to more
      than five million tons in the year 2013. Metabolic engineering constantly
      improves productivities of amino acid producing strains, mainly Corynebacterium
      glutamicum and Escherichia coli strains. Classical mutagenesis and screening have
      been accelerated by combination with intracellular metabolite sensing. Synthetic
      biology approaches have allowed access to new carbon sources to realize a
      flexible feedstock concept. Moreover, new pathways for amino acid production as
      well as fermentative production of non-native compounds derived from amino acids
      or their metabolic precursors were developed. These include dipeptides,
      alpha,omega-diamines, alpha,omega-diacids, keto acids, acetylated amino acids and
      omega-amino acids. 

PMID- 24922336
TI  - Intravenously administered indocyanine green may cause falsely high near-infrared
      cerebral oximetry readings.
AB  - BACKGROUND: Near-infrared spectroscopy assesses cerebral tissue oxygen saturation
      (Scto2) based on the absorption spectra of oxygenated and deoxygenated
      hemoglobin. It has been reported that IV-administered dyes including methylene
      blue, indigo carmine, and indocyanine green (ICG) may cause falsely low-pulse
      oximetry readings (Spo2). Although methylene blue and indigo carmine may also
      decrease Scto2, the effect of ICG has not been documented. METHODS: Simultaneous
      changes in the heart rate, arterial blood pressure, Scto2, and Spo2 were measured
      after IV administration of ICG (12.5 mg diluted in 5.0 mL 0.9% NaCl) in 15
      patients undergoing carotid endarterectomy under sevoflurane-remifentanil
      anesthesia. RESULTS: After the dye administration, no change in heart rate or
      arterial blood pressure was observed in any patient. Scto2 increased by 13.3+/
      4.0 percentage points, reaching the peak at 42.0+/-28.4 seconds after the
      administration, whereas Spo2 decreased by 1.9+/-1.2 percentage points, reaching
      the peak at 64.0+/-42.5 seconds (P<0.0001 both). CONCLUSIONS: ICG falsely
      increases the spectroscopy-determined cerebral oxygen saturation for up to 12
      minutes but dampens pulse oximetry readings.

PMID- 24922335
TI  - Pyrene chromophores for the photoreversal of psoralen interstrand crosslinks.
AB  - Applying psoralen interstrand crosslinks for the photoactivation of nucleic acids
      is a new concept. To find chromophores that can efficiently stimulate crosslink
      repair we screened several pyrenes and appended them to peptide nucleic acids for
      their site-selective addressing. Even though pyrenes conjugated to uracil
      revealed desirable spectroscopic properties they were not effective in crosslink
      reversal. In contrast, bare pyrenes are well suitable for crosslink repair with
      350 nm light showing an uncaging efficiency similar to classical photocaging
      groups. 

PMID- 24922337
TI  - Prolonged mechanical ventilation is associated with pulmonary complications,
      increased length of stay, and unfavorable discharge destination among patients
      with subdural hematoma.
AB  - BACKGROUND: Although subdural hematoma (SDH) is common in neurocritical practice,
      little is known about SDH patients requiring prolonged mechanical ventilation
      (PMV). We aimed to determine predictors of PMV and its relationship with outcome
      in patients with SDH. METHODS: SDH patients admitted to Rush University
      neurointensive care unit from January 2009 to March 2012 were reviewed. Duration
      of intubation, pulmonary complications, demographics, treatment, discharge
      disposition, and length of stay (LOS) were reviewed. PMV was defined as duration
      of intubation >4 days. Univariate and multivariate analyses were performed to
      identify predictors of PMV and association with outcome among survivors with SDH.
      RESULTS: Of the 288 survivors with SDH, the mean age was 68, and of them 179 were
      male. A total of 137 required surgical SDH evacuation. Pneumonia occurred in 26
      patients. Forty-eight patients (17%) required intubation, with duration of
      intubation being 1 to 20 days (median 3.0). Factors independently associated with
      PMV included alcohol abuse (OR, 4.31; 95% CI, 1.36-13.67), admission GCS<15 (OR,
      11; 95% CI, 2.36-51.52), and surgical evacuation (OR, 9.27; 95% CI, 1.93-44.54).
      PMV predicted pneumonia (OR, 5.85; 95% CI, 1.52-22.57), tracheostomy (OR, 26.67;
      95% CI, 2.93-242.67), increased LOS, and unfavorable discharge destination (OR,
      73.1; 95% CI, 14.03-380.69). CONCLUSIONS: PMV is associated with pulmonary
      complications, increased LOS, and unfavorable discharge destination in patients
      with SDH. Alcohol abuse, admission GCS, and surgical evacuation are associated
      with PMV among patients with SDH. Future studies should investigate the role of
      early tracheostomy in high-risk patients and impact on outcomes.

PMID- 24922338
TI  - Use of tracheal tube as a splint to prevent intraoperative kinking of gas
      sampling line.

PMID- 24922339
TI  - Spatial and temporal variation in type 1 diabetes incidence in Western Australia
      from 1991 to 2010: increased risk at higher latitudes and over time.
AB  - This study analysed spatial and temporal variation in childhood incidence of type
      1 diabetes mellitus (T1DM) among Western Australia's 36 Health Districts from
      1991 to 2010. There was a strong latitudinal gradient of 3.5% (95% CI, 0.2-7.2)
      increased risk of T1DM per degree south of the Equator, as averaged across the
      range 15-35 degrees  south. This pattern is consistent with the hypothesis of
      vitamin D deficiency at higher latitudes. In addition there was a 2.4% (95% CI,
      1.3-3.6) average increase in T1DM incidence per year. These effects could not be
      explained by population density, socioeconomic status, remoteness or ethnicity. 

PMID- 24922340
TI  - Incidence of unplanned oophorectomy at laparoscopic ovarian cystectomy for
      clinically benign cysts.
AB  - Laparoscopic surgery is the preferred approach in women with ovarian cysts and a
      low risk of malignancy, and the aim in young women should be to preserve the
      ovary. We are not aware of any data on the success of conservative surgery in
      preserving the affected ovary and this is the reason why we decided to
      investigate the incidence of unplanned oophorectomy, when a woman is originally
      scheduled for laparoscopic ovarian cystectomy for clinically benign cysts. We
      reviewed the medical notes of the 123 women who underwent surgery for clinically
      benign ovarian cysts between November 2004 and May 2012. The operative procedures
      performed were ovarian cystectomies (n = 119), salpingo-oophorectomy (n = 2) and
      fenestration (n = 2). In total, 61 women underwent a concomitant procedure. In
      our study, we found that planned laparoscopic cystectomy was mostly successful,
      with only 1.6% of patients in our series requiring unplanned oophorectomy.

PMID- 24922341
TI  - Dinuclear Cu(I) complexes of pyridyl-diazadiphosphetidines and
      aminobis(phosphonite) ligands: synthesis, structural studies and
      antiproliferative activity towards human cervical, colon carcinoma and breast
      cancer cells.
AB  - The copper(i) complexes containing phosphorus donor ligands such as
      diazadiphosphetidine, cis-{(o-OCH2C5H4N)P(MU-N(t)Bu)}2 (1) and
      aminobis(phosphonite), C6H5N{P(OC6H3(OMe-o)(C3H5-p))2}2 (2, PNP), have been
      synthesized. Treatment of 1 with copper iodide afforded the 1D coordination
      polymer [{Cu(MU-I)}2{(o-OCH2C5H4N)P(MU-N(t)Bu)}2]n (3). Treatment of 3 with 2,2'
      bipyridine (bpy) and 1,10-phenanthroline (phen) produced mixed-ligand complexes
      [(L)2Cu2{(o-OCH2C5H4N)P(MU-N(t)Bu)}2][I]2 (4 L = bpy; 5 L = phen) in good yields.
      The reaction of 2 with copper iodide yielded a rare tetranuclear copper complex
      [(CuI)2C6H5N(PR2)2]2 (6), which on subsequent treatment with various pyridyl
      ligands produced binuclear complexes [{Cu(MU-I)(py)}2(MU-PNP)] (7), [Cu2(MU
      I)(bpy)2(MU-PNP)]I (8), [Cu2(MU-I)I(bpy)(MU-PNP)] (9), [Cu2(phen)(bpy)(MU
      PNP)](OTf)2 (10), [Cu2(MU-I)I(phen)(MU-PNP)] (11) and [Cu2(MU-I)(phen)2(MU-PNP)]I
      (12), in an almost quantitative yield. The new copper(i) complexes (4, 5 and 7
      12) were tested for anti-cancer activity against three human tumor cell lines.
      Compounds 5, 10 and 12 showed in vitro antitumor activity 5-7 fold higher than
      cisplatin, the most used anticancer drug. These three most potent compounds (5,
      10 and 12) were chosen for detailed study to understand their mechanism of
      action. The copper(i) compounds studied in the present investigation were found
      to inhibit tumor cell growth by arresting cells at the S-phase of the cell cycle.
      The characteristic nuclear morphology of treated cells showed signs of DNA
      damage. The experimental evidence clearly indicated that these compounds
      initiated apoptosis, which is mediated through the p53 pathway. 

PMID- 24922343
TI  - Relaxation pathways of photoexcited iodide-methanol clusters: a computational
      investigation.
AB  - Upon photoexcitation of iodide-methanol clusters, I(-)(CH3OH)n, to a charge
      transfer-to-solvent (CTTS) excited state, extensive relaxation was found to
      occur, accompanied by a convoluted modulation of the stability of the excited
      electron, which ultimately decreases substantially. In order to develop a
      molecular-level understanding of the relaxation processes of CTTS excited I(
      )(CH3OH)n, high-level quantum chemical calculations are first used to investigate
      the ground, excited, and ionized states of I(-)(CH3OH)n (n = 2). Because of the
      relatively small size of I(-)(CH3OH)2, it was possible to characterize the
      contributions of solvent-solvent interactions to the stability of the CTTS
      excited cluster relative to dissociation into methanol, iodine, and a free
      electron, which exhibits a substantial dependence on the cluster geometric
      configuration. Ab initio molecular dynamics simulations of CTTS excited I(
      )(CH3OH)3 are then performed to shed some light onto the nature of the relaxation
      pathways involved in the modulation of the stability of the excited electron in
      larger clusters. Simulation results suggest that separation of I and (CH3OH)3(-)
      accompanied by solvent reorganization in the latter can initially stabilize the
      excited electron, while gradual cluster fragmentation to I, (CH3OH)2(-), and
      CH3OH ultimately destabilizes it. This work shows, for the first time, that the
      inability of small CTTS excited I(-)(CH3OH)n to retain a solvated electron may be
      attributed to the limited hydrogen-bonding capacity of CH3OH, which increases the
      propensity for fragmentation to smaller clusters with lower excess-electron
      binding energies, and highlights the critical role of intricate molecular
      interactions in the electron solvation process. 

PMID- 24922342
TI  - Small-colony variants and phenotype switching of intracellular Staphylococcus
      aureus in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) has been linked to the gram-positive
      bacteria Staphylococcus aureus (S. aureus) in its biofilm or intracellular forms.
      Recent evidence suggests that S. aureus also exists in a small-colony variant
      (SCV) form as a mechanism of altering its virulence capabilities. The aim of this
      study was to investigate the presence of SCVs in sinonasal mucosa of CRS patients
      and whether the phenomenon of phenotype switching can be applied to intracellular
      epithelial infections. METHODS: Sinonasal specimens were examined for the
      presence of intramucosal S. aureus and characterized to the strain level. An
      airway epithelial cell culture infection model was utilized to investigate
      whether bacteria were capable of alterations in virulence phenotype. RESULTS:
      Intramucosal organisms harvested from sinonasal biopsies demonstrate phenotypic
      growth patterns and lack of coagulase activity consistent with SCVs.
      Intracellular infection of airway epithelial cell cultures with S. aureus led to
      decreased secretion of enterotoxins and phenotypic growth alterations consistent
      with SCVs. CONCLUSIONS: Regulation of S. aureus virulence factors is a dynamic
      process, and exposure to the intracellular environment appears to provide the
      necessary conditions to enable these alterations in an attempt for the bacterium
      to survive and persist within host tissues. Further work is required to ascertain
      whether SCVs in CRS hold a clinically relevant pathogenic role in recalcitrant
      disease.

PMID- 24922345
TI  - One-step synthesis of graphene/polyaniline hybrids by in situ intercalation
      polymerization and their electromagnetic properties.
AB  - A new method is introduced for the preparation of graphene/polyaniline hybrids
      using a one-step intercalation polymerization of aniline inside the expanded
      graphite. The structural and morphological characterizations were performed by X
      ray diffraction analysis, transmission electron microscopy and field emission
      scanning electron microscopy. Both the experimental and first-principles
      simulated results show that the aniline cation formed by aniline and H(+) tends
      to be drawn towards the electron-enriched zone and to intercalate into the
      interlayer of graphite. Subsequently, an in situ polymerization leads to the
      separation of graphite into graphene sheet, resulting from the exothermic effect
      and more vigorous movements of the chain molecules of polyaniline. The
      interactions between polyaniline and graphene were confirmed by Fourier transform
      infrared spectroscopy and Raman spectra. In addition, the graphene/polyaniline
      hybrid exhibited a breakthrough in the improvement of microwave absorption. 

PMID- 24922347
TI  - Beyond Cairo: sexual and reproductive rights of young people in the new
      development agenda.
AB  - At the 1994 United Nations International Conference on Population and Development
      (ICPD), women's rights advocates fundamentally shifted the way the global
      development community views poverty, gender equality and reproductive rights.
      While the ICPD's call to action led to a marked improvement in reproductive
      health, more remains to be done to secure the sexual and reproductive rights and
      health of all, particularly for young people. As we approach the 20-year
      anniversary of Cairo, several global processes are happening concurrently that
      have implications for the future of the sexual and reproductive health and rights
      agenda, including the 20-year review of progress towards achieving the Cairo
      Programme of Action, the review of the Millennium Development Goals, and the open
      group discussions about the sustainable development goals and the new development
      agenda post-2015. There are five key areas of action where significant investment
      is needed moving forward to ensure young people's access and safeguard their
      rights: repeal outdated laws and create new policies that safeguard young
      people's health and rights; provide youth-friendly sexual and reproductive health
      services; guarantee young people's access to information and education; end
      gender discrimination and ensure government accountability. 

PMID- 24922346
TI  - Hypoxia-induced changes in protein s-nitrosylation in female mouse brainstem.
AB  - Exposure to hypoxia elicits an increase in minute ventilation that diminishes
      during continued exposure (roll-off). Brainstem N-methyl-D-aspartate receptors
      (NMDARs) and neuronal nitric oxide synthase (nNOS) contribute to the initial
      hypoxia-induced increases in minute ventilation. Roll-off is regulated by
      platelet-derived growth factor receptor-beta (PDGFR-beta) and S
      nitrosoglutathione (GSNO) reductase (GSNOR). S-nitrosylation inhibits activities
      of NMDAR and nNOS, but enhances GSNOR activity. The importance of S-nitrosylation
      in the hypoxic ventilatory response is unknown. This study confirms that
      ventilatory roll-off is virtually absent in female GSNOR(+/-) and GSNO(-/-) mice,
      and evaluated the location of GSNOR in female mouse brainstem, and temporal
      changes in GSNOR activity, protein expression, and S-nitrosylation status of
      GSNOR, NMDAR (1, 2A, 2B), nNOS, and PDGFR-beta during hypoxic challenge. GSNOR
      positive neurons were present throughout the brainstem, including the nucleus
      tractus solitarius. Protein abundances for GSNOR, nNOS, all NMDAR subunits and
      PDGFR-beta were not altered by hypoxia. GSNOR activity and S-nitrosylation status
      temporally increased with hypoxia. In addition, nNOS S-nitrosylation increased
      with 3 and 15 minutes of hypoxia. Changes in NMDAR S-nitrosylation were detected
      in NMDAR 2B at 15 minutes of hypoxia. No hypoxia-induced changes in PDGFR-beta S
      nitrosylation were detected. However, PDGFR-beta phosphorylation increased in the
      brainstems of wild-type mice during hypoxic exposure (consistent with roll-off),
      whereas it did not rise in GSNOR(+/-) mice (consistent with lack of roll-off).
      These data suggest that: (1) S-nitrosylation events regulate hypoxic ventilatory
      response; (2) increases in S-nitrosylation of NMDAR 2B, nNOS, and GSNOR may
      contribute to ventilatory roll-off; and (3) GSNOR regulates PDGFR-beta
      phosphorylation. 

PMID- 24922348
TI  - B-type natriuretic peptide trends after pediatric heart transplantation.
AB  - BNP is increasingly utilized in the management of pediatric HT recipients.
      Performing a retrospective single-center chart review, we sought to describe BNP
      changes during the first year after HT and identify factors that affect its
      trend. After exclusion for rejection, 316 BNP levels from 50 patients were
      evaluated. BNP underwent an exponential decline 120 days after HT followed by a
      plateau. Log10 BNP decline strongly correlated with time (r = -0.70, p < 0.0001).
      Initial BNP was less in pretransplant VAD (p = 0.0016) and lower post-HT inotrope
      use (p = 0.0043). Infant recipients, IT >4 h, and those bridged medically were
      associated with higher plateau BNP. Multivariable logistic regression
      demonstrated IT >4 h independently predicted plateau BNP in the upper quartile
      (OR 7.1, p = 0.02). No significant change in BNP coincided with rejection (N = 6
      patients) without severe hemodynamic compromise. BNP correlated modestly with
      right atrial pressure (r = 0.4652, p < 0.0001) and pulmonary capillary wedge
      pressure (r = 0.2660, p < 0.001), but poorly with echocardiogram (r = -0.18, p =
      0.003). Trending BNP could help provide insight into how the graft recovers after
      HT and IT >4 h independently predicted higher plateau BNP and may reflect subtle
      changes in graft performance. 

PMID- 24922349
TI  - Neuroanatomical correlates of categorizing emotional valence.
AB  - Categorization is fundamental to cognition, and evidence suggests that
      categorizing emotional stimuli holds a privileged position in human information
      processing. According to theories on embodied emotion, the subjective emotional
      feeling elicited by a stimulus plays a causal role in its categorization. Using
      functional MRI, we tested the hypothesis that categorizing emotional stimuli in
      terms of valence would activate structures involved in valence-specific
      experience of emotion. On each trial, two pictures from the International
      Affective Picture System were presented successively. Upon viewing the second
      picture, participants categorized it as belonging to the same valence category as
      or a different valence category from the first picture. Categorization activated
      an exclusively left-lateralized set of regions implicated in taxonomic
      categorization (i.e. judging whether two items are of the same kind) including
      the middle temporal gyrus and precuneus, as well as the posterior cingulate
      cortex. Critically, for negative pictures categorization activated structures
      that underlie the experience of negative emotions (anterior insula, left
      orbitofrontal cortex), whereas for positive pictures categorization activated
      structures that underlie the experience of positive emotions (dorsomedial and
      ventromedial prefrontal cortex). Consistent with predictions derived from
      theories on embodied emotion, these results suggest that experience of emotion
      contributes to categorizing emotional valence.

PMID- 24922350
TI  - SIRT2 mediates oxidative stress-induced apoptosis of differentiated PC12 cells.
AB  - Sirtuin 2 (SIRT2) is a member of the sirtuin family. Previous studies have
      suggested that SIRT2 mediates the cell death in models of Parkinson's disease and
      Huntington's disease. However, the role of SIRT2 in oxidative stress-induced cell
      death has remained unclear. In this study, we investigated the roles of SIRT2 in
      oxidative stress-induced cell death using differentiated PC12 cells as a cell
      model. We found that H2O2 induced a significant increase in the SIRT2 level in
      the cells. Both SIRT2 silencing and the SIRT2 inhibitor AGK2 significantly
      decreased H2O2-induced apoptosis, partially by inhibiting caspase-3 activation.
      We further found that silencing of SIRT2 led to decreased reactive oxygen species
      levels in the H2O2-treated cells. Collectively, our observations have suggested
      that SIRT2 plays a significant role in oxidative stress-induced cell death.

PMID- 24922352
TI  - Photo- and bio-reactivity patterns of dissolved organic matter from biomass and
      soil leachates and surface waters in a subtropical wetland.
AB  - Dissolved organic carbon (DOC) measurements and optical properties were applied
      to assess the photo- and bio-reactivity of dissolved organic matter (DOM) from
      different sources, including biomass leaching, soil leaching and surface waters
      in a subtropical wetland ecosystem. Samples were exposed to light and/or dark
      incubated through controlled laboratory experiments. Changes in DOC, ultraviolet
      (UV-Vis) visible absorbance, and excitation-emission matrix (EEM) fluorescence
      combined with parallel factor analysis (PARAFAC) were performed to assess sample
      degradation. Degradation experiments showed that while significant amounts of DOC
      were consumed during bio-incubation for biomass leachates, a higher degree of bio
      recalcitrance for soil leachate and particularly surface waters was displayed.
      Photo- and bio-humification transformations were suggested for sawgrass,
      mangrove, and seagrass leachates, as compared to substantial photo-degradation
      and very little to almost no change after bio-incubation for the other samples.
      During photo-degradation in most cases the EEM-PARAFAC components displayed photo
      decay as compared to a few cases which featured photo-production. In contrast
      during bio-incubation most EEM-PARAFAC components proved to be mostly bio
      refractory although some increases and decreases in abundance were also observed.
      Furthermore, the sequential photo- followed by bio-degradation showed, with some
      exceptions, a "priming effect" of light exposure on the bio-degradation of DOM,
      and the combination of these two processes resulted in a DOM composition more
      similar to that of the natural surface water for the different sub-environments.
      In addition, for leachate samples there was a general enrichment of one of the
      EEM-PARAFAC humic-like component (Ex/Em: <260(305)/416 nm) during photo
      degradation and an enrichment of a microbial humc-like component (Ex/Em:
      <260(325)/406 nm and of a tryptophan-like component (Ex/Em: 300/342 nm) during
      the bio-degradation process. This study exemplifies the effectiveness of optical
      property and EEM-PARAFAC in the assessment of DOM reactivity and highlights the
      importance of the coupling of photo- and bio-degradation processes in DOM
      degradation.

PMID- 24922351
TI  - Functional effects of mutations in the tropomyosin-binding sites of tropomodulin1
      and tropomodulin3.
AB  - Tropomodulins (Tmods) interact with tropomyosins (TMs) via two TM-binding sites
      and cap the pointed ends of TM-coated actin filaments. To study the functional
      interplay between TM binding and TM-actin filament capping by Tmods, we
      introduced disabling mutations into the first, second, or both TM-binding sites
      of full-length Tmod1 (Tmod1-L27G, Tmod1-I131D, and Tmod1-L27G/I131D,
      respectively) and full-length Tmod3 (Tmod3-L29G, Tmod3-L134D, and Tmod3
      L29G/L134D, respectively). Tmod1 and Tmod3 showed somewhat different TM-binding
      site utilization, but nearly all TM binding was abolished in Tmod1-L27G/I131D and
      Tmod3-L29G/L134D. Disruption of Tmod-TM binding had a modest effect on Tmod1's
      ability and no effect on Tmod3's ability to stabilize TM-actin pointed ends
      against latrunculin A-induced depolymerization. However, disruption of Tmod-TM
      binding did significantly impair the ability of Tmod3 to reduce elongation rates
      at pointed ends with alpha/betaTM, albeit less so with TM5NM1, and not at all
      with TM5b. For Tmod1, disruption of Tmod-TM binding only slightly impaired its
      ability to reduce elongation rates with alpha/betaTM and TM5NM1, but not at all
      with TM5b. Thus, Tmod-TM binding has a greater influence on Tmods' ability to
      inhibit subunit association as compared to dissociation from TM-actin pointed
      ends, particularly for alpha/betaTM, with Tmod3's activity being more dependent
      on TM binding than Tmod1's activity. Nevertheless, disruption of Tmod1-TM binding
      precluded Tmod1 targeting to thin filament pointed ends in cardiac myocytes,
      suggesting that the functional effects of Tmod-TM binding on TM-coated actin
      filament capping can be significantly modulated by the in vivo conformation of
      the pointed end or other factors in the intracellular environment.

PMID- 24922353
TI  - A Tire-Sulfur Hybrid Adsorption Denitrification (T-SHAD) process for
      decentralized wastewater treatment.
AB  - Nitrogen discharges from decentralized wastewater treatment (DWT) systems
      contribute to surface and groundwater contamination. However, the high
      variability in loading rates, long idle periods and lack of regular maintenance
      presents a challenge for biological nitrogen removal in DWT. A Tire-Sulfur Hybrid
      Adsorption Denitrification (T-SHAD) process was developed that combines nitrate
      (NO3(-)) adsorption to scrap tire chips with sulfur-oxidizing denitrification.
      This allows the tire chips to adsorb NO3(-) when the influent loading exceeds the
      denitrification capacity of the biofilm and release it when NO3(-) loading rates
      are low (e.g. at night). Three waste products, scrap tire chips, elemental sulfur
      pellets and crushed oyster shells, were used as a medium in adsorption, leaching,
      microcosm and up-flow packed bed bioreactor studies of NO3(-) removal from
      synthetic nitrified DWT wastewater. Adsorption isotherms showed that scrap tire
      chips have an adsorption capacity of 0.66 g NO3(-)-N kg(-1) of scrap tires.
      Leaching and microcosm studies showed that scrap tires leach bioavailable organic
      carbon that can support mixotrophic metabolism, resulting in lower effluent SO4(2
      ) concentrations than sulfur oxidizing denitrification alone. In column studies,
      the T-SHAD process achieved high NO3(-)-N removal efficiencies under steady state
      (90%), variable flow (89%) and variable concentration (94%) conditions.

PMID- 24922354
TI  - Effects of mechanical disintegration of activated sludge on the activity of
      nitrifying and denitrifying bacteria and phosphorus accumulating organisms.
AB  - The purpose of the study was to analyse the impact of hydrodynamic disintegration
      of thickened excess activated sludge, performed at different levels of energy
      density (70, 140 and 210 kJ/L), on the activity of microorganisms involved in
      nutrient removal from wastewater, i.e. nitrifiers, denitrifiers and phosphorus
      accumulating organisms (PAOs). Ammonium and nitrogen utilisation rates and
      phosphorus release rates for raw and disintegrated sludge were determined using
      batch tests. The experiment also included: 1) analysis of organic and nutrient
      compound release from activated sludge flocs, 2) determination of the sludge
      disintegration degree (DD), and 3) evaluation of respiratory activity of the
      biomass by using the oxygen uptake rate (OUR) batch test. It was shown that the
      activity degree of the examined groups of microorganisms depended on energy
      density and related sludge disintegration degree, and that inactivation of
      individual groups of microorganisms occurred at different values of DD. Least
      resistant to the destruction of activated sludge flocs turned out to be
      phosphorus accumulating organisms, while the most resistant were denitrifiers. A
      decrease of 20-40% in PAO activity was noted already at DD equal to 3-5%. The
      threshold values of DD, after crossing which the inactivation of nitrifiers and
      denitrifiers occurred, were equal to 8% and 10%, respectively. At lesser DD
      values an increase in the activity of these groups of microorganisms was
      observed, averaging 20.2-41.7% for nitrifiers and 9.98-36.3% for denitrifiers.

PMID- 24922355
TI  - Combined EUS and CT for evaluating gastrointestinal submucosal tumors before
      endoscopic resection.
AB  - GOALS: The aim of this study was to evaluate the combination of endoscopic
      ultrasonography (EUS) and computed tomography (CT) in predicting the maneuvers
      for therapeutic endoscopy for gastrointestinal submucosal tumors (SMTs). METHODS:
      Patients with SMTs, who were scheduled for endoscopic resection, were randomized
      to preoperative performance of both EUS and CT (group A) or EUS only (group B).
      The following data were collected: therapeutic maneuvers, duration of procedure,
      dose of propofol, resected lesion size, and complications. RESULTS: A total of 36
      patients were included in group A and 36 patients were included in group B.
      Endoscopic submucosal excavation was performed in 43 patients, endoscopic full
      thickness resection in 18 patients, and submucosal tunneling endoscopic resection
      in 11 patients. No significant differences were observed between the two groups
      (P>0.05). The coincidence rate between the preoperative program and the actual
      endoscopic procedures in group A was higher than that in group B (83.3 vs. 61.1%,
      P<0.05). The procedural time in group A was less than that in group B (39.36+/
      17.83 vs. 48.06+/-12.03 min, P<0.05), and the dose of propofol in group A was
      less than that in group B (249.18+/-125.12 vs. 304.16+/-102.61 mg, P<0.05). The
      mean resected lesion size was 2.32+/-1.46 cm in group A and 2.12+/-0.75 cm in
      group B, without differences (P>0.05). A total of 14 cardiopulmonary
      complications and seven endoscopic complications occurred, without significant
      differences between the two groups (P>0.05). CONCLUSION: EUS combined with CT can
      better evaluate SMTs compared with EUS only in predicting the maneuvers for
      therapeutic endoscopy.

PMID- 24922356
TI  - Angiogenesis and proliferation markers in adjacent cirrhotic tissue could predict
      hepatocellular carcinoma outcome after liver transplantation.
AB  - INTRODUCTION: The current staging systems for hepatocellular carcinoma (HCC) do
      not sufficiently predict outcomes after liver transplantation (LT). The present
      study assessed whether some tissue markers related to proliferation and
      angiogenesis have prognostic value. PATIENTS AND METHODS: The expression of CD34,
      vascular endothelial growth factor (VEGF), VEGFR2, VEGFR1, angiopoietin-1,
      angiopoietin-2, TIE2, COX-2, and proliferating cell nuclear antigen (PCNA) in
      tumor and adjacent cirrhotic tissue samples from 36 patients with HCC (n=10 with
      tumor recurrence after LT) was determined by immunochemistry. Microvessel density
      was assessed by CD34 staining and the PCNA labeling index calculated as the
      percentage of positive cells among at least 1000 hepatocyte nuclei studied in
      each sample using the computer program ContimUZ. VEGF, VEGFR2, VEGFR-1,
      angiopoietin-1, angiopoietin-2, TIE2, and COX-2 staining were evaluated by two
      blinded pathologists. The tumor recurrence rate was analyzed after a minimum
      follow-up of 36 months. RESULTS: A higher proliferation index in both tumor and
      adjacent cirrhotic tissue was related to HCC recurrence. The proliferation index
      in tumor tissue was also related to microvascular invasion. High expression
      (staining in >=50% of hepatocytes) of COX2 [P=0.025, odds ratio (OR)=7.5, 95%
      confidence interval (CI) 1.3-43.4], VEGF (P=0.01, OR=12, 95% CI 1.8-80.4), and
      its receptor VEGFR-2 (P=0.02, OR=8.5, 95% CI 1.4-49.5) in cirrhotic liver tissue,
      but not tumor tissue, was related to HCC recurrence after LT. CONCLUSION: A high
      proliferation index in tumor and cirrhotic tissue and high expression levels of
      some angiogenic markers in adjacent cirrhotic tissue could be predictive of tumor
      recurrence after LT.

PMID- 24922357
TI  - Small bowel capsule endoscopy in obscure gastrointestinal bleeding: normalcy is
      not reassuring.
AB  - BACKGROUND/AIM: Small bowel capsule endoscopy (SBCE) is currently a fundamental
      tool in the etiological study of obscure gastrointestinal bleeding (OGIB).
      However, the impact of a negative exam and the risk of rebleeding are not
      entirely known. The aim of this study was to evaluate the outcomes of patients
      with OGIB and a negative SBCE examination in terms of follow-up duration,
      additional diagnostic studies, and achievement of a diagnosis as well as to
      assess the incidence of rebleeding and possible associated factors. MATERIALS AND
      METHODS: We retrospectively analyzed 256 patients who consecutively underwent an
      SBCE examination for the study of OGIB between April 2006 and December 2011, and
      then selected the 79 whose results excluded potentially bleeding lesions. Eleven
      patients were lost to follow-up and the remaining 68 were eligible for a nested
      case-control analysis. Pre-SBCE and post-SBCE information was collected,
      including follow-up interval and incidence of rebleeding, defined as admission to
      the hospital for symptomatic anemia, need for blood transfusion, decrease in
      hemoglobin value of greater than 2 g/dl, or evidence of melena or hematochezia.
      Univariate analysis included age, sex, OGIB presentation (occult or visible),
      hemoglobin levels at presentation, and comorbidities. RESULTS: In the 68 patients
      analyzed, the mean age was 52+/-18 years and 61.8% were women. The OGIB was
      occult in 54 patients (79.4%) and overt in 14 patients (20.6%). Patients were
      followed up for an average of 32 months. Thirty-nine patients (57.4%) underwent
      further diagnostic investigations during the period of follow-up and a cause for
      the gastrointestinal bleeding was found in five of them. Rebleeding was
      documented in 16 (23.5%) patients, occurring on average 15+/-13.8 months after
      the SBCE. Male sex was associated significantly with higher incidence of
      rebleeding (P=0.004). CONCLUSION: Approximately one quarter of patients with OGIB
      and negative SBCE examination will experience rebleeding, with higher incidence
      among men; thus, a negative SBCE in this setting is not reassuring. As the vast
      majority of rebleeding episodes seem to occur within the following 2 years after
      SBCE, the maintenance of regular medical surveillance during the above-mentioned
      period of time after a negative SBCE seems advisable.

PMID- 24922358
TI  - Vapor sensing characteristics of nanoelectromechanical chemical sensors
      functionalized using surface-initiated polymerization.
AB  - Surface-initiated polymerization has been used to grow thick, uniform poly(methyl
      methacrylate) films on nanocantilever sensors. Cantilevers with these coatings
      yielded significantly greater sensitivity relative to bare devices as well as
      relative to devices that had been coated with drop-cast polymer films. The
      devices with surface-initiated polymer films also demonstrated high selectivity
      toward polar analytes. Surface-initiated polymerization can therefore provide a
      straightforward, reproducible method for large-scale functionalization of
      nanosensors. 

PMID- 24922359
TI  - Experimental and numerical investigation of contact-area-limited doping for top
      contact pentacene thin-film transistors with Schottky contact.
AB  - Effects of contact-area-limited doping for pentacene thin-film transistors with a
      bottom-gate, top-contact configuration were investigated. The increase in the
      drain current and the effective field-effect mobility was achieved by preparing
      hole-doped layers underneath the gold contact electrodes by coevaporation of
      pentacene and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ),
      confirmed by using a thin-film organic transistor advanced simulator (TOTAS)
      incorporating Schottky contact with a thermionic field emission (TFE) model.
      Although the simulated electrical characteristics fit the experimental results
      well only in the linear regime of the transistor operation, the barrier height
      for hole injection and the gate-voltage-dependent hole mobility in the pentacene
      transistors were evaluated with the aid of the device simulation. This
      experimental data analysis with the simulation indicates that the highly-doped
      semiconducting layers prepared in the contact regions can enhance the charge
      carrier injection into the active semiconductor layer and concurrent trap filling
      in the transistor channel, caused by the mitigation of a Schottky energy barrier.
      This study suggests that both the contact-area-limited doping and the device
      simulation dealing with Schottky contact are indispensable in designing and
      developing high-performance organic thin-film transistors. 

PMID- 24922362
TI  - How Lewis acidity of the cationic framework affects KNaNbOF(5) polymorphism.
AB  - The valence matching principle is used to explain the loss of inversion symmetry
      in the noncentrosymmetric (NCS) polymorph of KNaNbOF5 in comparison to its
      centrosymmetric (CS) polymorph. The [NbOF5](2-) anion has five contacts to both
      potassium and sodium in the NCS polymorph, whereas in the CS polymorph there are
      only four contacts to potassium and six contacts to sodium. The lower average
      Lewis acidity of the cationic framework in the NCS polymorph relative to the CS
      polymorph reflects the loss of inversion symmetry. This lower average Lewis
      acidity is achieved during hydrothermal synthesis with a potassium-rich solution
      when the K:Na ratio in the reaction is greater than 1:1, as the Lewis acidity of
      potassium is lower than that of sodium. The contrasting coordination environments
      are manifested in secondary distortions that weaken the primary Nb?O interaction
      and lengthen the Nb?O bond in the NCS polymorph. An unusual heat-induced phase
      transition from the CS to the NCS polymorph was studied with in situ powder X-ray
      diffraction. The transition to the NCS polymorph upon cooling occurs through an
      intermediate phase(s). 

PMID- 24922360
TI  - Platelet factor 4 protects bone marrow mesenchymal stem cells from acute
      radiation injury.
AB  - OBJECTIVE: The aim of this study was to find a new radiation protector, platelet
      factor 4 (PF4) and to identify its effect on haemopoietic microenvironment in
      vitro and in vivo. METHODS: Radiation damage on bone marrow mesenchymal stem
      cells ex and in vitro was set up as models. Growth curve analysis, clonogenic
      survival assay, FACSCaliburTM (BD Immunocytometry Systems, San Jose, CA), 5
      ethynyl-2'-deoxyuridine immunofluorescence staining and quantitative reverse
      transcription-polymerase chain reaction were employed to assess the
      characterization of bone marrow mesenchymal stem cells (BMSCs), proliferation,
      apoptosis, cell cycle and gene expression. RESULTS: A dose- and time-dependent
      enhancement of cell viability and survival was observed for PF4 treatment along
      with 500 cGy gamma-radiation in vitro. The same phenomena were noted in vivo,
      including enhancement of adherence and proliferation ability while inhibition of
      cell apoptosis, which were associated with a short-term decrease in the G0/G1
      ratio owing to S phase arrest. These were accompanied with enhanced Bcl-2
      expression and p53/p21 loss. CONCLUSION: These results uncover that PF4 might be
      a novel therapeutic approach, which could reduce DNA damage and increase survival
      of BMSCs, in part, by inhibiting p53/p21 axis and facilitating DNA damage repair.
      ADVANCES IN KNOWLEDGE: This study explores the feasibility of a new
      radioprotector and hence may be clinically important.

PMID- 24922363
TI  - Structure reconstruction of TiO2-based multi-wall nanotubes: first-principles
      calculations.
AB  - A new method of theoretical modelling of polyhedral single-walled nanotubes based
      on the consolidation of walls in the rolled-up multi-walled nanotubes is
      proposed. Molecular mechanics and ab initio quantum mechanics methods are applied
      to investigate the merging of walls in nanotubes constructed from the different
      phases of titania. The combination of two methods allows us to simulate the
      structures which are difficult to find only by ab initio calculations. For
      nanotube folding we have used (1) the 3-plane fluorite TiO2 layer; (2) the
      anatase (101) 6-plane layer; (3) the rutile (110) 6-plane layer; and (4) the 6
      plane layer with lepidocrocite morphology. The symmetry of the resulting single
      walled nanotubes is significantly lower than the symmetry of initial coaxial
      cylindrical double- or triple-walled nanotubes. These merged nanotubes acquire
      higher stability in comparison with the initial multi-walled nanotubes. The wall
      thickness of the merged nanotubes exceeds 1 nm and approaches the corresponding
      parameter of the experimental patterns. The present investigation demonstrates
      that the merged nanotubes can integrate the two different crystalline phases in
      one and the same wall structure. 

PMID- 24922364
TI  - Efficiency improvement by polarization-reversed electron blocking structure in
      GaN-based Light-emitting diodes.
AB  - Polarization-reversed electron-blocking structure, which had negative
      polarization charges localized at the interface between the last quantum barrier
      (LQB) and electron-blocking layer (EBL), was demonstrated to remarkably improve
      the light-emitting efficiency of GaN-based blue light-emitting diodes (LEDs)
      numerically and experimentally. The improvement was attributed to the enhanced
      electron-blocking effectiveness by the elevated conduction band nearby the
      LQB/EBL interface. Nevertheless, the efficiency droop was not mitigated because
      the decrease of electron-leakage was accompanied by the increase of Auger
      recombination. 

PMID- 24922361
TI  - Adiposity, fractional exhaled nitric oxide, and asthma in U.S. children.
AB  - RATIONALE: Whether allergic airway inflammation mediates the association between
      overweight or obesity and childhood asthma is unknown. OBJECTIVES: To examine
      adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children.
      METHODS: Cross-sectional study of indicators of adiposity or obesity, FeNO (a
      biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged
      6-17 years in the 2007-2010 National Health and Nutrition Examination Survey.
      Adiposity measures included body mass index (BMI), percent body fat (PBF), and
      waist circumference (WC). MEASUREMENTS AND MAIN RESULTS: BMI, PBF, and WC were
      associated with asthma among children with low FeNO (odds ratio, 1.54-1.68; P <
      0.01), but not among children with increased FeNO. Among children without asthma,
      BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC.
      Among children with asthma and a high FeNO, all adiposity indicators were
      associated with decreased FEV1/FVC (beta = -1.5% to -1.7% per z score) but not
      with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or
      control in children with asthma and increased FeNO, but not in children with
      asthma and low FeNO. Similar results were obtained in a secondary multivariate
      analysis of overweight or obesity (defined as BMI >=85th percentile) and asthma
      or indicators of asthma severity or control, stratified by FeNO level.
      CONCLUSIONS: Adiposity indicators are associated with asthma in children with low
      FeNO. Among children with asthma, adiposity indicators are associated with worse
      asthma severity or control in those with high FeNO.

PMID- 24922365
TI  - UV polarization lidar for remote sensing new particles formation in the
      atmosphere.
AB  - Understanding new particles formation in the free troposphere is key for air
      quality and climate change, but requires accurate observation tools. Here, we
      discuss on the optical requirements ensuring a backscattering device, such as a
      lidar, to remotely observe nucleation events promoted by nonspherical desert dust
      or volcanic ash particles. By applying the Mie theory and the T-matrix code, we
      numerically simulated the backscattering coefficient of spherical freshly
      nucleated particles and nonspherical particles. We hence showed that, to remotely
      observe such nucleation events with an elastic lidar device, it should operate in
      the UV spectral range and be polarization-resolved. Two atmospheric case studies
      are proposed, on nucleation events promoted by desert dust, or volcanic ash
      particles. This optical pathway might be useful for climate, geophysical and
      fundamental purposes, by providing a range-resolved remote observation of
      nucleation events. 

PMID- 24922366
TI  - Cooperative electromagnetic interactions between nanoparticles for solar energy
      harvesting.
AB  - The cooperative electromagnetic interactions between discrete resonators have
      been widely used to modify the optical properties of metamaterials. Here we
      propose a general approach for engineering these interactions both in the dipolar
      approximation and for any higher-order description. Finally we apply this
      strategy to design broadband absorbers in the visible range from simple n-ary
      arrays of metallic nanoparticles. 

PMID- 24922367
TI  - RCWA and FDTD modeling of light emission from internally structured OLEDs.
AB  - We report on the fabrication and simulation of a green OLED with an Internal
      Light Extraction (ILE) layer. The optical behavior of these devices is simulated
      using both Rigorous Coupled Wave Analysis (RCWA) and Finite Difference Time
      Domain (FDTD) methods. Results obtained using these two different techniques show
      excellent agreement and predict the experimental results with good precision. By
      verifying the validity of both simulation methods on the internal light
      extraction structure we pave the way to optimization of ILE layers using either
      of these methods. 

PMID- 24922368
TI  - A novel integrated structure of thin film GaN LED with ultra-low thermal
      resistance.
AB  - This study proposes a novel packaging structure for vertical thin-GaN LED
      applications by integration of LED chip and silicon-based packaging process. The
      vertical thin film LED is directly mounted on package submount. The shortest
      thermal path structure from junction to package submount achieves the lowest
      thermal resistance of 1.65 K/W for LED package. Experimental results indicate
      that low thermal resistance significant improved forward current up to 4.6A with
      1.125 * 1.125 mm2 LED chip size.

PMID- 24922369
TI  - Annealing of SnO2 thin films by ultra-short laser pulses.
AB  - Post-deposition annealing by ultra-short laser pulses can modify the optical
      properties of SnO2 thin films by means of thermal processing. Industrial grade
      SnO2 films exhibited improved optical properties after picosecond laser
      irradiation, at the expense of a slightly increased sheet resistance [Proc. SPIE
      8826, 88260I (2013)]. The figure of merit phi = T10 / R(sh) was increased up to
      59% after laser processing. In this paper we study and discuss the causes of this
      improvement at the atomic scale, which explain the observed decrease of
      conductivity as well as the observed changes in the refractive index n and
      extinction coefficient k. It was concluded that the absorbed laser energy
      affected the optoelectronic properties preferentially in the top 100-200 nm
      region of the films by several mechanisms, including the modification of the
      stoichiometry, a slight desorption of dopant atoms (F), adsorption of hydrogen
      atoms from the atmosphere and the introduction of laser-induced defects, which
      affect the strain of the film.

PMID- 24922370
TI  - Zinc oxide nanowire arrays for silicon core/shell solar cells.
AB  - The optics of core / shell nanowire solar cells was investigated. The optical
      wave propagation was studied by finite difference time domain simulations using
      realistic interface morphologies. The interface morphologies were determined by a
      3D surface coverage algorithm, which provides a realistic film formation of
      amorphous silicon films on zinc oxide nanowire arrays. The influence of the
      nanowire dimensions on the interface morphology and light trapping was
      investigated and optimal dimensions of the zinc oxide nanowire were derived. 

PMID- 24922371
TI  - Optoelectrical characteristics of green light-emitting diodes containing thick
      InGaN wells with digitally grown InN/GaN.
AB  - Compared with conventionally grown thin InGaN wells, thick InGaN wells with
      digitally grown InN/GaN exhibit superior optical properties. The activation
      energy (48 meV) of thick InGaN wells (generated by digital InN/GaN growth from
      temperature-dependent integrated photoluminescence intensity) is larger than the
      activation energy (25 meV) of conventionally grown thin InGaN wells. Moreover,
      thick InGaN wells with digitally grown InN/GaN exhibit a smaller sigma value (the
      degree of localization effects) of 19 meV than that of conventionally grown thin
      InGaN wells (23 meV). Compared with green light-emitting diodes (LEDs) with
      conventional thin InGaN wells, the improvement in 20-A/cm2 output power for LEDs
      containing thick InGaN wells with digitally grown InN/GaN is approximately 23%.

PMID- 24922372
TI  - Antireflection-enhanced color by a natural graded refractive index (GRIN)
      structure.
AB  - Nanostructured materials like graded refractive index (GRIN) structures in moth
      eyes have inspired the design of novel antireflective coatings. Such structures
      are more flexible than uniform coatings, but applications have been mainly
      limited to broadband antireflection in solar cells and LEDs. Here we show that
      cylindrical pigment granules in two bird species (Polyplectron bicalcaratum and
      Patagioenas fasciata) form a GRIN that suppresses interference and expands the
      range of colors produced by a multilayer. These results demonstrate that a GRIN
      structure can function like a pigment (i.e. through selective, independent
      wavelength blocking) to generate unique colors and may inspire the design of
      novel antireflective and structurally colored coatings. 

PMID- 24922373
TI  - Nanoimprinted backside reflectors for a-Si:H thin-film solar cells: critical role
      of absorber front textures.
AB  - The development of optimal backside reflectors (BSRs) is crucial for future low
      cost and high efficiency silicon (Si) thin-film solar cells. In this work,
      nanostructured polymer substrates with aluminum coatings intended as BSRs were
      produced by positive and negative nanoimprint lithography (NIL) techniques, and
      hydrogenated amorphous silicon (a-Si:H) was deposited hereon as absorbing layers.
      The relationship between optical properties and geometry of front textures was
      studied by combining experimental reflectance spectra and theoretical
      simulations. It was found that a significant height variation on front textures
      plays a critical role for light-trapping enhancement in solar cell applications.
      As a part of sample preparation, a transfer NIL process was developed to overcome
      the problem of low heat deflection temperature of polymer substrates during solar
      cell fabrication. 

PMID- 24922374
TI  - Effects of InGaN layer thickness of AlGaN/InGaN superlattice electron blocking
      layer on the overall efficiency and efficiency droops of GaN-based light emitting
      diodes.
AB  - The operating voltage, light output power, and efficiency droops of GaN-based
      light emitting diodes (LEDs) were improved by introducing Mg-doped AlGaN/InGaN
      superlattice (SL) electron blocking layer (EBL). The thicker InGaN layers of
      AlGaN/InGaN SL EBL could have a larger effective electron potential height and
      lower effective hole potential height than that of AlGaN EBL. This thicker InGaN
      layer could prevent electron leakage into the p-region of LEDs and improve hole
      injection efficiency to achieve a higher light output power and less efficiency
      droops with the injection current. The low lateral resistivity of Mg-doped
      AlGaN/InGaN SL would have superior current spreading at high current injection. 

PMID- 24922375
TI  - Novel broadband glass phosphors for high CRI WLEDs.
AB  - New broadband glass phosphors with excellent thermal stability were proposed and
      experimentally demonstrated for white light-emitting-diodes (WLEDs). The novel
      glass phosphors were realized through dispersing multiple phosphors into SiO2
      based glass (SiO2-Na2O-Al2O3-CaO) at 680 degrees C. Y3Al5O12:Ce3+ (YAG),
      Lu3Al5O12:Ce3+ (LuAG), and CaAlSiN3: Eu2+ (nitride) phosphor crystals were chosen
      respectively as the yellow, green, and red emitters of the glass phosphors. The
      effect of sintering temperature on inter-diffusion reduction between phosphor
      crystals and amorphous SiO2 in nitride-doped glass phosphors was studied and
      evidenced by the aid of high-resolution transmission electron microscopy (HRTEM).
      Broadband glass phosphors with high quantum-yield of 55.6% were thus successfully
      realized through the implementation of low sintering temperature. Proof-of
      concept devices utilizing the novel broadband phosphors were developed to
      generate high-quality cool-white light with trisstimulus coordinates (x, y) =
      (0.358, 0.288), color-rending index (CRI) = 85, and correlated color temperature
      (CCT) = 3923K. The novel broadband glass phosphors with excellent thermal
      stability are essentially beneficial to the applications for next-generation
      solid-state indoor lighting, especially in the area where high power and absolute
      reliability are required.

PMID- 24922376
TI  - InAs/GaAsSb quantum dot solar cells.
AB  - The hybrid structure of GaAs/GaAsSb quantum well (QW)/InAs quantum dots solar
      cells (QDSCs) is analyzed using power-dependent and temperature-dependent
      photoluminescence. We demonstrate that placing the GaAsSb QW beneath the QDs
      forms type-II characteristics that initiate at 12% Sb composition. Current
      density-voltage measurements demonstrate a decrease in power efficiency with
      increasing Sb composition. This could be attributed to increased valence band
      potential in the GaAsSb QW that subsequently limits hole transportation in the QD
      region. To reduce the confinement energy barrier, a 2 nm GaAs wall is inserted
      between GaAsSb QW and InAs QDs, leading to a 23% improvement in power efficiency
      for QDSCs. 

PMID- 24922377
TI  - Light diffraction by concentrator Fresnel lenses.
AB  - Fresnel lenses are widely used in concentrating photovoltaic (CPV) systems as
      primary optical elements focusing sunlight onto small solar cells or onto
      entrance apertures of secondary optical elements attached to the solar cells.
      Calculations using the Young-Maggi-Rubinowicz theory of diffraction yield
      analytical expressions for the amount of light spilling outside these target
      areas due to diffraction at the edges of the concentrator Fresnel lenses.
      Explicit equations are given for the diffraction loss due to planar Fresnel
      lenses with small prisms and due to arbitrarily shaped Fresnel lenses.
      Furthermore, the cases of illumination by monochromatic, polychromatic, totally
      spatially coherent and partially spatially coherent light (e.g. from the solar
      disc) are treated, resulting in analytical formulae. Examples using realistic
      values show losses due to diffraction of up to several percent. 

PMID- 24922378
TI  - Enhancement of light-extraction efficiency of organic light-emitting diodes using
      silica nanoparticles embedded in TiO2 matrices.
AB  - We investigate two types of internal light-extraction layer structures for
      organic light-emitting diodes (OLEDs) that consist of silica nanoparticles (NPs)
      embedded in high-refractive-index TiO2 matrices. The composite of silica NPs and
      TiO2 matrices was coated on the glass substrate and fabricated with and without a
      SiO2 planarization layer. An increase in the optical out-coupling efficiency by a
      factor of 2.0 was obtained at a high luminance of 3,000 cd/m2 from OLEDs
      containing the silica NPs embedded in TiO2 matrices between glass substrates and
      Zn-doped In2O3 (IZO) electrodes after additional planarization processes. This is
      consistent with the analytical result using the finite-difference time-domain
      (FDTD) method. Randomly distributed silica NPs acting as scattering centers could
      reduce the optical loss when extracting light. By using additional planarization
      processes with a PECVD-derived SiO2 layer, one can assure that smoother surfaces
      provide higher out-coupling efficiency, which attain 100% and 97% enhancements in
      power (lm/W) and current (cd/A) efficiencies, respectively.

PMID- 24922379
TI  - Maximal power output by solar cells with angular confinement.
AB  - Angularly selective filters can increase the efficiency of radiatively limited
      solar cells. A restriction of the acceptance angle is linked to the kind of
      utilizable solar spectrum (global or direct radiation). This has to be considered
      when calculating the potential enhancement of both the efficiency and the power
      output. In this paper, different concepts to realize angularly selective filters
      are compared regarding their limits for efficiency and power output per unit
      area. First experimental results of a promising system based on a thin-film
      filter as the angularly selective element are given to demonstrate the practical
      relevance of such systems. 

PMID- 24922380
TI  - Wafer-scale surface roughening for enhanced light extraction of high power
      AlGaInP-based light-emitting diodes.
AB  - A new approach to surface roughening was established and optimized in this paper
      for enhancing the light extraction of high power AlGaInP-based LEDs, by combining
      ultraviolet (UV) assisted imprinting with dry etching techniques. In this
      approach, hexagonal arrays of cone-shaped etch pits are fabricated on the surface
      of LEDs, forming gradient effective-refractive-index that can mitigate the
      emission loss due to total internal reflection and therefore increase the light
      extraction efficiency. For comparison, wafer-scale FLAT-LEDs without any surface
      roughening, WET-LEDs with surface roughened by wet etching, and DRY-LEDs with
      surface roughened by varying the dry etching time of the AlGaInP layer, were
      fabricated and characterized. The average output power for wafer-scale FLAT-LEDs,
      WET-LEDs, and DRY3-LEDs (optimal) at 350 mA was found to be 102, 140, and 172 mW,
      respectively, and there was no noticeable electrical degradation with the WET
      LEDs and DRY-LEDs. The light output was increased by 37.3% with wet etching, and
      68.6% with dry etching surface roughening, respectively, without compromising the
      electrical performance of LEDs. A total number of 1600 LED chips were tested for
      each type of LEDs. The yield of chips with an optical output power of 120 mW and
      above was 0.3% (4 chips), 42.8% (684 chips), and 90.1% (1441 chips) for FLAT
      LEDs, WET-LEDs, and DRY3-LEDs, respectively. The dry etching surface roughening
      approach developed here is potentially useful for the industrial mass production
      of wafer-scale high power LEDs. 

PMID- 24922381
TI  - Broadband down-conversion for silicon solar cell by ZnSe/phosphor
      heterostructure.
AB  - Down-conversion is a feasible way to improve conversion efficiency of silicon
      solar cell. However, the width of excitation band for down-converter based on
      trivalent lanthanide ions is still not satisfying. Here, we designed and
      fabricated a heterostructural down-converter composed of Y2O3: [(Tb3+-Yb3+), Li+]
      quantum cutting phosphor and ZnSe. The ZnSe phase was used to absorb the incident
      light with energy larger than its bandgap, and transfer the energy to Tb3+-Yb3+
      quantum cutting couple. Short-wavelength incident light was finally converted
      into a strong Yb3+ emission at about 1000 nm, locating at the maximal spectral
      response of silicon solar cell. The excitation band of the down-conversion covers
      a wide region of 250-550 nm. Benefiting from the energy match between ZnSe
      bandgap and 7F6->5D4 absorption of Tb3+ ions, the bandwidth of down-conversion is
      almost maximized.

PMID- 24922382
TI  - Planar waveguide LED illuminator with controlled directionality and divergence.
AB  - We present a versatile illumination system where white light emitting diodes are
      coupled through a planar waveguide to periodically patterned extraction features
      at the focal plane of a two dimensional lenslet array. Adjusting the position of
      the lenslet array allows control over both the directionality and divergence of
      the emitted beam. We describe an analytic design process, and show optimal
      designs can achieve high luminous emittance (1.3x104 lux) over a 2x2 foot
      aperture with over 75% optical efficiency while simultaneously allowing beam
      steering over +/- 60 degrees  and divergence control from +/- 5 degrees  to fully
      hemispherical output. Finally, we present experimental results of a prototype
      system which validate the design model.

PMID- 24922383
TI  - Highly reliable Ti-based ohmic contact to N-polar n-type GaN for vertical
      geometry light-emitting diodes by using a Ta barrier layer.
AB  - The formation of thermally stable and low resistance Ti/Al-based ohmic contacts
      to N-polar n-GaN for high-power vertical light-emitting diodes (VLEDs) using a Ta
      diffusion barrier is presented. Before annealing, both Ti/Al/Au and Ti/Ta/Al/Au
      contacts reveal ohmic behavior with specific contact resistances of 2.4 * 10-4
      and 1.2 * 10-4 Omegacm2, respectively. However, unlike the Ti/Al/Au samples that
      are electrically degraded with increasing annealing time at 250  degrees C, the
      Ti/Ta/Al/Au samples remain thermally stable even after annealing for 600 min.
      LEDs fabricated with the Ti/Ta/Al/Au contacts yield 8.3% higher output power (at
      300 mA) than LEDs with the Ti/Al/Au contact. X-ray photoemission spectroscopy
      results show that the Ta layer serves as an efficient barrier to the indiffusion
      of oxygen toward the GaN. On the basis of the XPS and electrical results, the
      annealing dependence of the electrical characteristics of Ti/Al-based contacts
      are described and discussed.

PMID- 24922384
TI  - The use of the adding-doubling method for the optical optimization of planar
      luminescent down shifting layers for solar cells.
AB  - To enhance the efficiency of solar cells, a luminescent down shifting layer can
      be applied in order to adapt the solar spectrum to the spectral internal quantum
      efficiency of the semiconductor. Optimization of such luminescent down shifting
      layers benefits from quick and direct evaluation methods. In this paper, the
      potential of the adding-doubling method is investigated to simulate the optical
      behavior of an encapsulated solar cell including a planar luminescent down
      shifting layer. The results of the adding-doubling method are compared with
      traditional Monte Carlo ray tracing simulations. The average relative deviation
      is found to be less than 1.5% for the absorptance in the active layer and the
      reflectance from the encapsulated cell, while the computation time can be
      decreased with a factor 52. Furthermore, the adding-doubling method is adopted to
      investigate the suitability of the SrB4O7:5%Sm2 + ,5%Eu2 + phosphor as a
      luminescent down shifting material in combination with a Copper Indium Gallium
      Selenide solar cell. A maximum increase of 9.0% in the short-circuit current can
      be expected if precautions are taken to reduce the scattering by matching the
      refractive index of host material to the phosphor particles. To be useful as
      luminescent down shifting material, the minimal value of the quantum yield of the
      phosphor is determined to be 0.64. 

PMID- 24922386
TI  - Reducing the efficiency droop by lateral carrier confinement in InGaN/GaN quantum
      well nanorods.
AB  - Efficiency droop is a major obstacle facing high-power application of InGaN/GaN
      quantum-well (QW) light-emitting diodes (LEDs). In this paper, we report the
      suppression of efficiency droop induced by the process of density-activated
      defect recombination in nanorod structures of a-plane InGaN/GaN QWs. In the high
      carrier density regime, the retained emission efficiency in a dry-etched nanorod
      sample is observed to be over two times higher than that in its parent QW sample.
      We further argue that such improvement is a net effect that the lateral carrier
      confinement overcomes the increased surface trapping introduced during
      fabrication. 

PMID- 24922385
TI  - On the mechanisms of InGaN electron cooler in InGaN/GaN light-emitting diodes.
AB  - Electron overflow limits the quantum efficiency of InGaN/GaN light-emitting
      diodes. InGaN electron cooler (EC) can be inserted before growing InGaN/GaN
      multiple quantum wells (MQWs) to reduce electron overflow. However, detailed
      mechanisms of how the InGaN EC contributes to the efficiency improvement have
      remained unclear so far. In this work, we theoretically propose and
      experimentally demonstrate an electron mean-free-path model, which reveals the
      InGaN EC reduces the electron mean free path in MQWs, increases the electron
      capture rate and also reduces the valence band barrier heights of the MQWs, in
      turn promoting the hole transport into MQWs. 

PMID- 24922387
TI  - Multilayer nanoparticle arrays for broad spectrum absorption enhancement in thin
      film solar cells.
AB  - In this paper, we present a theoretical study on the absorption efficiency
      enhancement of a thin film amorphous Silicon (a-Si) photovoltaic cell over a
      broad spectrum of wavelengths using multiple nanoparticle arrays. The light
      absorption efficiency is enhanced in the lower wavelengths by a nanoparticle
      array on the surface and in the higher wavelengths by another nanoparticle array
      embedded in the active region. The efficiency at intermediate wavelengths is
      enhanced by the simultaneous resonance from both nanoparticle layers. We optimize
      this design by tuning the radius of particles in both arrays, the period of the
      array and the distance between the two arrays. The optimization results in a
      total quantum efficiency of 62.35% for a 0.3 MUm thick a-Si substrate. 

PMID- 24922388
TI  - GaN-based light-emitting diodes on graphene-coated flexible substrates.
AB  - We demonstrate GaN-based thin light-emitting diodes (LEDs) on flexible polymer
      and paper substrates covered with chemical vapor deposited graphene as a
      transparent-conductive layer. Thin LEDs were fabricated by lifting the sapphire
      substrate off by Excimer laser heating, followed by transfer of the LEDs to the
      flexible substrates. These substrates were coated with tri-layer graphene by a
      wet transfer method. Optical and electrical properties of thin laser lift-offed
      LEDs on the flexible substrates were characterized under both relaxed and
      strained conditions. The graphene on paper substrates remained conducting when
      the graphene/paper structure was folded. The high transmittance, low sheet
      resistance and high failure strain of the graphene make it an ideal candidate as
      the transparent and conductive layer in flexible optoelectronics. 

PMID- 24922389
TI  - Time domain simulation of tandem silicon solar cells with optimal textured light
      trapping enabled by the quadratic complex rational function.
AB  - Amorphous silicon/crystalline silicon (a-Si/c-Si) micromorph tandem cells, with
      best confirmed efficiency of 12.3%, have yet to fully approach their theoretical
      performance limits. In this work, we consider a strategy for improving the light
      trapping and charge collection of a-Si/c-Si micromorph tandem cells using random
      texturing with adjustable short-range correlations and long-range periodicity. In
      order to consider the full-spectrum absorption of a-Si and c-Si, a novel
      dispersion model known as a quadratic complex rational function (QCRF) is applied
      to photovoltaic materials (e.g., a-Si, c-Si and silver). It has the advantage of
      accurately modeling experimental semiconductor dielectric values over the entire
      relevant solar bandwidth from 300-1000 nm in a single simulation. This wide-band
      dispersion model is then used to model a silicon tandem cell stack (ITO/a-Si:H/c
      Si:H/silver), as two parameters are varied: maximum texturing height h and
      correlation parameter f. Even without any other light trapping methods, our front
      texturing method demonstrates 12.37% stabilized cell efficiency and 12.79 mA/cm2
      in a 2 MUm-thick active layer.

PMID- 24922390
TI  - Enhanced electroluminescence using Ta2O5/ZnO/HfO2 asymmetric double
      heterostructure in ZnO/GaN-based light emitting diodes.
AB  - ZnO/GaN-based light-emitting diodes (LEDs) with improved asymmetric double
      heterostructure of Ta2O5/ZnO/HfO2 have been fabricated. Electroluminescence (EL)
      performance has been enhanced by the HfO2 electron blocking layer and further
      improved by continuing inserting the Ta2O5 hole blocking layer. The origins of
      the emission have been identified, which indicated that the Ta2O5/ZnO/HfO2
      asymmetric structure could more effectively confine carriers in the active i-ZnO
      layer and meanwhile suppresses of radiation from GaN. This device exhibits
      superior stability in long-time running. It's hoped that the asymmetric double
      heterostructure may be helpful for the development of the future ZnO-based LEDs.

PMID- 24922391
TI  - Efficiency improvement of a vertical light-emitting diode through surface plasmon
      coupling and grating scattering.
AB  - The enhancement of output intensity, the generation of polarized output, and the
      reduction of the efficiency droop effect in a surface plasmon (SP) coupled
      vertical light-emitting diode (LED) with an Ag nano-grating structure located
      between the p-GaN layer and the wafer bonding metal for inducing SP coupling with
      the InGaN/GaN quantum wells (QWs) are demonstrated. In fabricating the vertical
      LED, the patterned sapphire substrate is removed with a photoelectrochemical
      liftoff technique. Based on the reflection measurement from the metal grating
      structure and the numerical simulation result, it is found that the localized
      surface plasmon (LSP) resonance induced around the metal grating crest plays the
      major role in the SP-QW coupling process although a hybrid mode of LSP and
      surface plasmon polariton can be generated in the coupling process. By adding a
      surface grating structure to the SP-coupled vertical LED on the n-GaN side, the
      output intensity is further enhanced, the output polarization ratio is further
      increased, and the efficiency droop effect is further suppressed. 

PMID- 24922392
TI  - Influence of V-pits on the efficiency droop in InGaN/GaN quantum wells.
AB  - We discuss the influence of V-pits and their energy barrier, originating from its
      facets of (101-1) planes, on the luminescence efficiency of InGaN LEDs.
      Experimental analysis using cathodoluminescence (CL) exhibits that thin facets of
      V-pits of InGaN quantum wells (QWs) appear to be effective in improving the
      emission intensity, preventing the injected carriers from recombining non
      radiatively with threading dislocations (TDs). Our theoretical calculation based
      on the self-consistent approach with adopting k?p method reveals that higher V
      pit energy barrier heights in InGaN QWs more efficiently suppress the non
      radiative recombination at TDs, thus enhancing the internal quantum efficiency
      (IQE). 

PMID- 24922393
TI  - Enhanced power conversion efficiency of quantum dot sensitized solar cells with
      near single-crystalline TiO2 nanohelixes used as photoanodes.
AB  - Photo-electrodes with tailored three-dimensional nanostructures offer a large
      enhancement in light harvesting capability for various optoelectronic devices
      enabled by strong light scattering in the nanostructures as well as improved
      charge transport. Here we present an array of three-dimensional titanium dioxide
      (TiO2) nanohelixes fabricated by the oblique angle deposition method as a
      multifunctional photoanode for CdSe quantum dot sensitized solar cells (QDSSCs).
      The CdSe QDSSC with a TiO2 nanohelix photoanode shows a 100% higher power
      conversion efficiency despite less light being absorbed in CdSe QDs when compared
      with a conventional TiO2 nanoparticle photoanode. We attribute the higher power
      conversion efficiency to strong light scattering by the TiO2 nanohelixes and much
      enhanced transport and collection of photo-generated carriers enabled by the
      unique geometry and near-single crystallinity of the TiO2 nanohelix structure.

PMID- 24922394
TI  - Aperiodic and randomized dielectric mirrors: alternatives to metallic back
      reflectors for solar cells.
AB  - Dielectric mirrors have recently emerged for solar cells due to the advantages of
      lower cost, lower temperature processing, higher throughput, and zero plasmonic
      absorption as compared to conventional metallic counterparts. Nonetheless, in the
      past, efforts for incorporating dielectric mirrors into photovoltaics were not
      successful due to limited bandwidth and insufficient light scattering that
      prevented their wide usage. In this work, it is shown that the key for ultra
      broadband dielectric mirrors is aperiodicity, or randomization. In addition, it
      has been proven that dielectric mirrors can be widely applicable to thin-film and
      thick wafer-based solar cells to provide for light trapping comparable to
      conventional metallic back reflectors at their respective optimal geometries.
      Finally, the near-field angular emission plot of Poynting vectors is conducted,
      and it further confirms the superior light-scattering property of dielectric
      mirrors, especially for diffuse medium reflectors, despite the absence of surface
      plasmon excitation. The preliminary experimental results also confirm the high
      feasibility of dielectric mirrors for photovoltaics. 

PMID- 24922395
TI  - Illumination of dense urban areas by light redirecting panels.
AB  - With the high population growth rate, especially in developing countries, and the
      scarcity of land resources, buildings are becoming so close to each other,
      depriving the lower floors and the alleys from sunlight and consequently causing
      health problems. Therefore, there is an urgent need for cost-effective efficient
      light redirecting panels that guide sun rays into those dim places. In this
      paper, we address this problem. A novel sine wave based panel is presented to
      redirect/diverge light downward and enhance the illumination level in those dark
      places. Simulation results show that the proposed panel improves the illuminance
      values by more than 200% and 400% in autumn and winter respectively, operates
      over wide solar altitude ranges, and redirects light efficiently. Experimental
      and simulation results are in good agreement. 

PMID- 24922396
TI  - Phase space considerations for light path lengths in planar, isotropic absorbers.
AB  - Fundamental limits for path lengths of light in isotropic absorbers are
      calculated. The method of calculation is based on accounting for occupied states
      in optical phase space. Light trapping techniques, such as scattering or
      diffraction, are represented by the way how the available states are occupied.
      One finding of the presented investigation is that the path length limit is
      independent of the light trapping mechanism and only depends on the conditions
      for light incidence to, and escape from the absorber. A further finding is that
      the maximum path length is obtained for every light trapping mechanisms which
      results in a complete filling of the available states in phase space. For
      stationary solar cells, the Yablonovitch limit of 4dn2, with n the refractive
      index of the absorber, is a very good approximation of this limit.

PMID- 24922397
TI  - Design of a high efficiency ultrathin CdS/CdTe solar cell using back surface
      field and backside distributed Bragg reflector.
AB  - A high efficiency CdS/CdTe solar cell was designed with a reduced CdTe absorber
      layer thickness and a distributed Bragg reflector (DBR) as an optical reflector
      and a ZnTe layer as back surface field (BSF) layer. Simulation results showed
      that with combination of DBR and BSF layers and 0.3 um thick CdTe, the conversion
      efficiency was increased about 3.2% as compared with a reference cell (with 4 um
      thick CdTe layer). It was also shown that the efficiency can be increased up to
      6.02% by using a long carrier lifetime in the absorber layer. Under global AM
      1.5G conditions, the proposed cell structure had an open-circuit voltage of 1.062
      V, a short-circuit current density of 24.64 mA/cm2, and a fill factor of 81.3%,
      corresponding to a total area conversion efficiency of 21.02%.

PMID- 24922398
TI  - Near-unity broadband absorption designs for semiconducting nanowire arrays via
      localized radial mode excitation.
AB  - We report design methods for achieving near-unity broadband light absorption in
      sparse nanowire arrays, illustrated by results for visible absorption in GaAs
      nanowires on Si substrates. Sparse (<5% fill fraction) nanowire arrays achieve
      near unity absorption at wire resonant wavelengths due to coupling into 'leaky'
      radial waveguide modes of individual wires and wire-wire scattering processes.
      From a detailed conceptual development of radial mode resonant absorption, we
      demonstrate two specific geometric design approaches to achieve near unity
      broadband light absorption in sparse nanowire arrays: (i) introducing multiple
      wire radii within a small unit cell array to increase the number of resonant
      wavelengths, yielding a 15% absorption enhancement relative to a uniform nanowire
      array and (ii) tapering of nanowires to introduce a continuum of diameters and
      thus resonant wavelengths excited within a single wire, yielding an 18%
      absorption enhancement over a uniform nanowire array. 

PMID- 24922399
TI  - High performance GaN-based flip-chip LEDs with different electrode patterns.
AB  - A high-performance flip-chip light-emitting diode (FCLED) with a Ni/Ag metallic
      film as high reflectivity mirror (92.67%) of p-type electrode was successfully
      fabricated. The effect of geometric electrode patterns on the blue InGaN/GaN LEDs
      was investigated and analyzed qualitatively its current spreading in the active
      region. With different electrode patterns, these devices were experimented and
      simulated by simple electrical circuits in order to confirm its current-voltage
      characteristics and light emission pattern. It was found that the forward
      voltages of these FCLEDs were about 3.6 V (@350 mA). The light output power of
      FCLEDs with circle-round type electrode was 368 mW at an injection current of 700
      mA. From these optoelectronic measurement and thermal infrared images, we
      proposed some design methodologies for improved current spreading, light output
      power, droop efficiency and thermal performance. 

PMID- 24922400
TI  - Retrieval of vertical particle concentration profiles by optical remote sensing:
      a model study.
AB  - Water-leaving radiance is subject to depth variability of the water constituents.
      The optical penetration depth is strongly dependent on the wavelength lambda,
      which allows to retrieve a non-uniform vertical profile of an optically-active
      constituent CTSM(z) from remote-sensing reflectance Rrs(lambda,Cz). We define the
      apparent particle concentration CTSM,app(lambda) of a vertically homogeneous
      water column whose Rrs(lambda,Cconst) matches Rrs(lambda,Cz). Subsequently, we
      define a vertically-weighted averaged particle concentration CTSM,ave(lambda),
      only dependent on CTSM(z), and retrieve CTSM(z) by minimizing the error between
      CTSM,app(lambda) and CTSM,ave(lambda) with genetic algorithms. We conclude that
      the retrieval is excellent if the sub-surface maximum lays close to the surface
      or the background concentration of CTSM(z) is low. Conversely, results worsen for
      opposite conditions, due to insufficient signal strength from superimposed sub
      surface maxima.

PMID- 24922402
TI  - Energy transfer in Eu3+ doped scheelites: use as thermographic phosphor.
AB  - In this paper the luminescence of the scheelite-based CaGd2(1-x)Eu2x(WO4)4 solid
      solutions is investigated as a function of the Eu content and temperature. All
      phosphors show intense red luminescence due to the 5D0 - 7F2 transition in Eu3+,
      along with other transitions from the 5D1 and 5D0 excited states. For high Eu3+
      concentrations the intensity ratio of the emission originating from the 5D1 and
      5D0 levels has a non-conventional temperature dependence, which could be
      explained by a phonon-assisted cross-relaxation process. It is demonstrated that
      this intensity ratio can be used as a measure of temperature with high spatial
      resolution, allowing the use of these scheelites as thermographic phosphor. The
      main disadvantage of many thermographic phosphors, a decreasing signal for
      increasing temperature, is absent.

PMID- 24922403
TI  - Enhanced light trapping in solar cells with a meta-mirror following generalized
      Snell's law.
AB  - As the performance of photovoltaic cells approaches the Shockley-Queisser limit,
      appropriate schemes are needed to minimize the losses without compromising the
      current performance. In this paper we propose a planar absorber-mirror light
      trapping structure where a conventional mirror is replaced by a meta-mirror with
      asymmetric light scattering properties. The meta-mirror is tailored to have
      reflection in asymmetric modes that stay outside the escape cone of the
      dielectric, hence trapping light with unit probability. Ideally, the meta-mirror
      can be designed to have such light trapping for any angle of incidence onto the
      absorber-mirror structure. We illustrate the concept by using a simple gap
      plasmon meta-mirror. Even though the response of the mirror is non-ideal with the
      unwanted scattering modes reducing the light absorption, we observe an order of
      magnitude enhancement compared to single pass absorption in the absorber. The
      bandwidth of the enhancement can be matched with the range of wavelengths close
      to the solar cell absorber band-edge where improved light absorption is required.

PMID- 24922404
TI  - Post-growth CdCl2 treatment on CdTe thin films grown on graphene layers using a
      close-spaced sublimation method.
AB  - We investigated the morphological, structural and optical properties of CdCl2
      treated cadmium telluride (CdTe) thin films deposited on defective graphene using
      a close-spaced sublimation (CSS) system. Heat treatment in the presence of CdCl2
      caused recrystallization of CSS-grown CdTe over the as-deposited structures. The
      preferential (111) orientation of as-deposited CdTe films was randomized after
      post-growth CdCl2 treatment. New small grains (bumps) on the surface of CdCl2
      treated CdTe films were ascribed to nucleation of the CdTe grains during the
      CdCl2 treatment. The properties of as-deposited and CdCl2-treated CdTe films were
      characterized by room temperature micro-photoluminescence, micro-Raman
      spectroscopy, scanning electron microscopy, and X-ray diffraction analysis. Our
      results are useful to demonstrate a substrate configuration CdTe thin film solar
      cells.

PMID- 24922405
TI  - Laterally assembled nanowires for ultrathin broadband solar absorbers.
AB  - We studied optical resonances in laterally oriented Si nanowire arrays by
      conducting finite-difference time-domain simulations. Localized Fabry-Perot and
      whispering-gallery modes are supported within the cross section of each nanowire
      in the array and result in broadband light absorption. Comparison of a nanowire
      array with a single nanowire shows that the current density (J(SC)) is preserved
      for a range of nanowire morphologies. The J(SC) of a nanowire array depends on
      the spacing of its constituent nanowires, which indicates that both diffraction
      and optical antenna effects contribute to light absorption. Furthermore, a
      vertically stacked nanowire array exhibits significantly enhanced light
      absorption because of the emergence of coupled cavity-waveguide modes and the
      mitigation of a screening effect. With the assumption of unity internal quantum
      efficiency, the J(SC) of an 800-nm-thick cross-stacked nanowire array is 14.0
      mA/cm2, which yields a ~60% enhancement compared with an equivalent bulk film
      absorber. These numerical results underpin a rational design strategy for
      ultrathin solar absorbers based on assembled nanowire cavities.

PMID- 24922406
TI  - Royal College of Obstetricians and Gynaecologists guidelines: how evidence-based
      are they?
AB  - Evidence-based medicine aims to translate scientific research into good medical
      practice. The Royal College of Obstetricians and Gynaecologists publishes
      recommendations and guidelines to guide clinicians in decision-making. In this
      study, the evidence base underlying the 'Green-top Guidelines' has been analysed
      in order to establish the quality of research underlying recommendations. During
      this descriptive study of 1,682 individual recommendations, the authors found
      that only 9-12% of the guidelines were based on the best quality (Grade A)
      evidence. The authors believe that this type of analysis serves to provide
      greater clarity for clinicians and patients using guidelines and recommendations
      in the field of obstetrics and gynaecology to make collaborative clinical
      decisions.

PMID- 24922407
TI  - Association between plasma apelin levels and coronary collateral development in
      patients with stable angina pectoris.
AB  - Apelin is an endogenous ligand for the orphan G protein-coupled receptor (APJ
      receptor). Apelin is predominantly expressed in endocardial and vascular
      endothelial cells, while APJ receptor is localized to endothelial and smooth
      muscle cells, and cardiomyocytes. Apelin has recently attracted much attention
      due to its promotive effects on angiogenesis and its protective effects against
      mycardial infarction. In this issue of Atherosclerosis, Akboga et al.
      investigated plasma apelin levels in patients with stable angina and severe
      coronary artery stenosis and provided the first evidence that higher plasma
      apelin levels are associated with better coronary collateral development,
      suggesting that apelin plays a role in coronary collateral development. 

PMID- 24922408
TI  - Interactions between intestinal microbiota and innate immune system in pediatric
      inflammatory bowel disease: Retraction.

PMID- 24922409
TI  - WGO's new member society and new training center.

PMID- 24922410
TI  - Absolute surface metrology by rotational averaging in oblique incidence
      interferometry.
AB  - A modified method for measuring the absolute figure of a large optical flat
      surface in synchrotron radiation by a small aperture interferometer is presented.
      The method consists of two procedures: the first step is oblique incidence
      measurement; the second is multiple rotating measurements. This simple method is
      described in terms of functions that are symmetric or antisymmetric with respect
      to reflections at the vertical axis. Absolute deviations of a large flat surface
      could be obtained when mirror antisymmetric errors are removed by N-position
      rotational averaging. Formulas are derived for measuring the absolute surface
      errors of a rectangle flat, and experiments on high-accuracy rectangle flats are
      performed to verify the method. Finally, uncertainty analysis is carried out in
      detail. 

PMID- 24922411
TI  - Noise tolerance in wavelength-selective switching of optical differential
      quadrature-phase-shift-keying pulse train by collinear acousto-optic devices.
AB  - Optical switching of high-bit-rate quadrature-phase-shift-keying (QPSK) pulse
      trains using collinear acousto-optic (AO) devices is theoretically discussed.
      Since the collinear AO devices have wavelength selectivity, the switched optical
      pulse trains suffer from distortion when the bandwidth of the pulse train is
      comparable to the pass bandwidth of the AO device. As the AO device, a sidelobe
      suppressed device with a tapered surface-acoustic-wave (SAW) waveguide and a
      Butterworth-type filter device with a lossy SAW directional coupler are
      considered. Phase distortion of optical pulse trains at 40 to 100  Gsymbols/s in
      QPSK format is numerically analyzed. Bit-error-rate performance with additive
      Gaussian noise is also evaluated by the Monte Carlo method.

PMID- 24922412
TI  - Efficient frequency doubling at 399 nm.
AB  - We describe a reliable, high-power, and narrow-linewidth laser source at 399 nm,
      which is useful for cooling and trapping of ytterbium atoms. A continuous-wave
      titanium-sapphire laser at 798 nm is frequency doubled using a lithium triborate
      crystal in an enhancement cavity. Up to 1.0 W of light at 399 nm has been
      obtained from 1.3 W of infrared light, with an efficiency of 80%.

PMID- 24922413
TI  - Circularly polarized light with high degree of circularity and low azimuthal
      error sensitivity.
AB  - The generation of circularly polarized light with a high circularity degree and
      low azimuthal error sensitivity was analyzed using a system composed by two
      waveplates. It is shown how the high circularity degree is achieved using a
      combination of a half- (lambda/2) and a quarter- (lambda/4) waveplate
      lambda/2+lambda/4 configuration. However, the lowest azimuthal sensitivity under
      small variations in the azimuths of the waveplates is obtained by employing a
      lambda/4+lambda/2 configuration. Analytical calculus particularized for quartz
      and MgF2 waveplates is presented.

PMID- 24922414
TI  - Eliminating bias drift error in lock-in frequency for a resonant fiber optic
      gyro.
AB  - The accuracy of the resonant frequency servo loop is a major concern for high
      performance operation of a resonant fiber optic gyro. This is usually resolved by
      adopting the central frequency of the laser source to track the resonance of the
      optical fiber ring resonator in one direction. However, the drift of the resonant
      frequency arising from resonator temperature fluctuation must be eliminated to
      maintain this accuracy. The traditional proportional integral (PI) frequency
      servo loop cannot address this issue very well. For instance, a bias error as
      large as tens or even hundreds of degrees/hour has been observed at the
      demodulated output of a resonant frequency servo loop. In this paper, we propose
      a method to eliminate this bias error by adding a double integral term in the
      traditional PI-based resonant frequency servo loop. We demonstrate that the
      double integral term can precisely track the linear resonant frequency drift,
      evidenced by our experimentally achieved close-to-zero bias error of -0.0009 
      deg/h at the demodulated output of the resonant frequency servo loop.

PMID- 24922415
TI  - Sub-nanometer flattening of 45 cm long, 45 actuator x-ray deformable mirror.
AB  - We have built a 45 cm long x-ray deformable mirror (XDM) of super-polished single
      crystal silicon that has 45 actuators along the tangential axis. After assembly,
      the surface height error was 19 nm rms. With use of high-precision visible-light
      metrology and precise control algorithms, we have actuated the XDM and flattened
      its entire surface to 0.7 nm rms controllable figure error. This is, to our
      knowledge, the first sub-nanometer active flattening of a substrate longer than
      15 cm.

PMID- 24922416
TI  - Novel calibration method for structured-light system with an out-of-focus
      projector.
AB  - A structured-light system with a binary defocusing technique has the potential to
      have more extensive application due to its high speeds, gamma-calibration-free
      nature, and lack of rigid synchronization requirements between the camera and
      projector. However, the existing calibration methods fail to achieve high
      accuracy for a structured-light system with an out-of-focus projector. This paper
      proposes a method that can accurately calibrate a structured-light system even
      when the projector is not in focus, making it possible for high-accuracy and high
      speed measurement with the binary defocusing method. Experiments demonstrate that
      our calibration approach performs consistently under different defocusing
      degrees, and a root-mean-square error of about 73 MUm can be achieved with a
      calibration volume of 150(H) mm*250(W) mm*200(D)mm.

PMID- 24922417
TI  - LED surgical lighting system with multiple free-form surfaces for highly sterile
      operating theater application.
AB  - Although the ventilation system is widely employed in the operating theater, a
      strictly sterile surgical environment still cannot be ensured because of laminar
      disturbance, which is mainly caused by the surgical lighting system. Abandoning
      traditional products, we propose an LED surgical lighting system, which can
      alleviate the laminar disturbance and provide an appropriate lighting condition
      for surgery. It contains a certain amount of LED lens units, which are embedded
      in the ceiling and arranged around the air supply smallpox. The LED lens unit
      integrated with an LED light source and a free-form lens is required to produce a
      uniform circular illumination with a large tolerance to the change of lighting
      distance. To achieve such a dedicated lens, two free-form refractive surfaces,
      which are converted into two ordinary differential equations by the design method
      presented in this paper, are used to deflect the rays. The results show that the
      LED surgical lighting system can provide an excellent illumination environment
      for surgery, and, apparently, the laminar disturbance also can be relieved. 

PMID- 24922418
TI  - Parastigmatic corneal surfaces.
AB  - Principal meridians of the corneal vertex of the human ocular system are not
      always orthogonal. To study these irregular surfaces at the vertex, which have
      principal meridians with an angle different from 90 degrees , we attempt to
      define so-called parastigmatic surfaces; these surfaces allow us to correct
      several classes of irregular astigmatism, with nonorthogonal principal meridians,
      using a simple refractive surface. We will create a canonical surface to describe
      the surfaces of the human cornea with a short and simple formula, using two
      additional parameters to the current prescription: the angle between principal
      meridians and parharmonic variation of curvatures between them. 

PMID- 24922419
TI  - Nonpolarizing color mirrors on a high-reflecting metal base.
AB  - Optically variable devices made from optical-interference coatings create
      chromatic color mirrors that have minimal polarization differences with
      increasing incidence angle. These metal-dielectric-metal designs produce
      narrowband, high reflectance in the visible wavelength region. Broader-band
      reflectance regions, similar to those created by multilayer dielectric stacks,
      can be replicated on a high-reflecting metal base such as aluminum, maintaining
      the same nonpolarizing effects of the narrowband designs. These designs are
      intended for reflective systems used for display where reduced angle sensitivity
      is paramount. However, these designs can also be adapted for large angular
      dependent color shift, such as in effect pigments. Design examples and layer
      material suggestions are given depending on the application requirements. 

PMID- 24922420
TI  - Terahertz gas sensing based on a simple one-dimensional photonic crystal cavity
      with high-quality factors.
AB  - We report in this paper terahertz gas sensing using a simple 1D photonic crystal
      cavity. The resonant frequencies of the cavity depend linearly on the refractive
      index of the ambient gas, which can then be measured by monitoring the resonance
      shift. Although quite easy to manufacture, this cavity exhibits high-quality
      factors, facilitating the realization of high sensitivity in the gas refractive
      index sensing. In our experiment, 6% of the change of hydrogen concentration in
      air, which corresponds to a refractive index change of 1.4*10-5, can be steadily
      detected, and different gas samples can be easily identified. Our experimental
      results are consistent with the theoretically calculated spectral responses of
      the cavity using the transfer matrix method.

PMID- 24922421
TI  - Role of modulation frequency in a hybrid Q-switched Nd:LuVO4 laser with an
      acousto-optic modulator and a Cr4+:YAG saturable absorber.
AB  - This study presents a hybrid Q-switched Nd:LuVO4 laser with an acousto-optic
      modulator (AOM) and a Cr4+:YAG saturable absorber. The importance of the
      modulation frequency of the AOM in this dual-loss modulation system is examined
      with two distinct observations: (1) the periodic-ramp pulse characteristics with
      the modulation frequency, and (2) the existence of the intrinsic modulation
      frequency for minimizing the pulsewidth. The shortest pulsewidth and the highest
      peak power were 10.6 ns and 13.9 kW, respectively, at a pump power of 10 W.
      Compared with the passively Q-switched laser, which has a pulsewidth of 18.3 ns,
      the ratio of pulse compression reaches 42%. Finally, numerical simulations based
      on the rate equations are used to verify the experimental results.

PMID- 24922422
TI  - Reduction of optical Kerr-effect induced error in a resonant micro-optic gyro by
      light-intensity feedback technique.
AB  - As a type of main optical error source in the resonant micro-optic gyro (RMOG),
      the optical Kerr-effect brings a nonzero bias to the output of the RMOG. The
      light-intensity fluctuations are interpreted as the cause. To eliminate the
      drifts due to the optical Kerr-effect, the intensities of the clockwise (CW) and
      counterclockwise (CCW) lightwaves circulating in the resonator should be equal at
      all times. Through theoretical analysis and experimental investigation, a linear
      relationship between the second-harmonic demodulated signal and the light
      intensity input to the resonator is demonstrated for the sinusoidally phase
      modulated RMOG. Both our numerical simulation and experimental verification are
      carried out, which, for the first time to the best of our knowledge, demonstrate
      that the second-harmonic demodulated signal can be used as a feedback error
      signal to reduce both the input-intensity mismatch between the CW and CCW
      lightwaves and their intensity fluctuations. By applying the light-intensity
      feedback loop to the closed-loop RMOG, the light-intensity fluctuations are
      reduced to 2.7*10-5, down from 5.86%. As a result, the optical-Kerr effect
      induced error is effectively reduced.

PMID- 24922423
TI  - Remote-focusing microscopy with long working distance objective lenses.
AB  - Remote-focusing microscopy has recently attracted a lot of interest due to its
      high-speed axial scanning capabilities. In this paper, we modeled remote-focusing
      microscopy, based on a pair of long working distance objective lenses. Three
      dimensional intensity distributions of the point spread functions (PSFs) are
      calculated, and no significant spherical aberrations are introduced over a large
      volume of 100  MUm*100  MUm*150  MUm. The validity of the scheme is verified by
      imaging biological samples and microelectronic chips at the imaging depth of 150
      MUm without introducing aberrations in the experiment.

PMID- 24922424
TI  - Simple far-field radiative thermal rectifier using Fabry-Perot cavities based
      infrared selective emitters.
AB  - We present a thermal rectification device concept based on far-field radiative
      exchange between two selective emitters. Rectification is achieved due to a large
      contrast between the two selective emitters' thermo-optical properties. A simple
      device constituted by two multilayer samples made of metallic (Au) and
      semiconductor (Si and HDSi) thin films is proposed. This device shows a
      rectification ratio increasing with temperature up to 19% for a temperature
      difference of DeltaT=370  K. Further optimization would allow larger
      rectification values. The presented results might be useful for energy conversion
      devices, engineering of smart radiative coolers/insulators, and development of
      thermal logical circuits.

PMID- 24922425
TI  - Compensation of polarization distortions in Faraday isolators by means of
      magnetic field inhomogeneity.
AB  - We propose a new type of Faraday isolator with compensation of the azimuthally
      symmetric component of polarization distortions by means of magnetic field
      inhomogeneity. The depolarization was attenuated in experiments by a factor of 7.

PMID- 24922426
TI  - Quality-guided phase unwrapping implementation: an improved indexed interwoven
      linked list.
AB  - Quality-guided phase unwrapping (QGPU) is a widely used technique, and an adjoin
      list plays a very important role in the QGPU process. Indexed interwoven linked
      list (I2L2) is a data structure for implementing the adjoin list. In this paper,
      we propose three improvements on the I2L2. The first improvement is resumed
      searching, which records the highest nonempty level in the I2L2 and reduces the
      computational redundancy; the second is an adaptive mapping between the quality
      values and the I2L2 levels, which reduces the effect of concentrated quality
      value distribution. Last, I2L2-H, a new variant of the I2L2 combining the
      advantages of both the I2L2 and heap, is developed. With these three
      improvements, the improved I2L2 is over 6 times faster than the original one in
      the best cases, and it can process large phase maps in almost real time. 

PMID- 24922427
TI  - Comparative study of ring and random cavities for fiber lasers.
AB  - An experimental comparison of three fiber laser structures with the same Raman
      gain medium is presented in order to establish the main pros and cons of each
      basic scheme. The first fiber laser is based on a hybrid ring-random fiber laser,
      the second one is a pure ring fiber laser, and the last one is a random fiber
      laser. Several aspects have been taken into account in the study. First, from the
      optical point of view, the parameters of interest compared are output power,
      lasing threshold, slope efficiency, power fluctuations, and the longitudinal
      modes have been analyzed. Second, the possible utilization of fiber lasers in
      digital modulated optical communication systems is also studied. 

PMID- 24922428
TI  - Spectral radiance source based on supercontinuum laser and wavelength tunable
      bandpass filter: the spectrally tunable absolute irradiance and radiance source.
AB  - A new spectrally tunable source for calibration of radiometric detectors in
      radiance, irradiance, or power mode has been developed and characterized. It is
      termed the spectrally tunable absolute irradiance and radiance source (STAIRS).
      It consists of a supercontinuum laser, wavelength tunable bandpass filter, power
      stabilization feedback control scheme, and output coupling optics. It has the
      advantages of relative portability and a collimated beam (low etendue), and is an
      alternative to conventional sources such as tungsten lamps, blackbodies, or
      tunable lasers. The supercontinuum laser is a commercial Fianium SC400-6-02,
      which has a wavelength range between 400 and 2500 nm and a total power of 6 W.
      The wavelength tunable bandpass filter, a PhotonEtc laser line tunable filter
      (LLTF), is tunable between 400 and 1000 nm and has a bandwidth of 1 or 2 nm
      depending on the wavelength selected. The collimated laser beam from the LLTF
      filter is converted to an appropriate spatial and angular distribution for the
      application considered (i.e., for radiance, irradiance, or power mode calibration
      of a radiometric sensor) with the output coupling optics, for example, an
      integrating sphere, and the spectral radiance/irradiance/power of the source is
      measured using a calibration optical sensor. A power stabilization feedback
      control scheme has been incorporated that stabilizes the source to better than
      0.01% for averaging times longer than 100 s. The out-of-band transmission of the
      LLTF filter is estimated to be < -65 dB (0.00003%), and is sufficiently low for
      many end-user applications, for example the spectral radiance calibration of
      earth observation imaging radiometers and the stray light characterization of
      array spectrometers (the end-user optical sensor). We have made initial
      measurements of two end-user instruments with the STAIRS source, an array
      spectrometer and ocean color radiometer.

PMID- 24922429
TI  - Tomography by point source digital holographic microscopy.
AB  - We propose a tomographic method for point source inline holographic microscopy.
      By recording a set of holograms at different illumination angles, shadowing
      effects are eliminated resulting in three-dimensional images with the same
      precision at the micrometer-scale in all directions. The advantage of our
      tomographic approach is that it works for both absorbing and phase objects,
      regardless of the change of refractive index at interfaces. We develop the method
      with computer simulations and demonstrate its strength by presenting experimental
      results for micrometer-sized polystyrene beads and a cotton fiber. 

PMID- 24922430
TI  - Plasmon hybridization in composite nanostructures with tunable resonances and
      vertex truncation analysis.
AB  - An Ag/SiO2/Ag sandwich delta nanostar with three sharp angles (30 degrees ) is
      proposed. The extinction efficiency property with a variation in environment
      refractive index has been investigated in detail by the finite difference time
      domain method. The refractive index response sensitivity is 482.67  nm/RIU. And
      the correlations between resonance wavelengths and thickness of the dielectric
      layer are also established. It reveals that as the thickness increases, the peak
      wavelength turns to red shift, and a tunable resonance wavelength is achieved
      through the thickness adjusting of the SiO2 layer. The maximum of the electric
      field enhancement is 833.776 with the thickness of the dielectric layer h=40  nm.
      Moreover, the influence of the vertex truncation on the extinction spectra and
      the refractive index sensitivity has also been analyzed.

PMID- 24922431
TI  - Green function method for the time domain simulation of pulse propagation.
AB  - Based on the Green function method, the nonlinear Schrodinger equation is
      directly solved in the time domain (without Fourier transform). Because the
      dispersion and nonlinear effects are calculated simultaneously, it does not bring
      any spurious effect such as the split-step method in which the step size has to
      be carefully controlled by an error estimation. By this time domain solution, the
      pulse fission is analyzed, and we obtain the relationship between the minimum T0
      (the half-width at 1/e-intensity point of a pulse) and dispersion coefficients
      (beta2, beta3, and beta4). Thus the concrete dispersion values, which have an
      impact on ultrashort pulses (the quantity units is femtosecond or attosecond),
      are listed. It has been demonstrated that pulse fission occurs in the normal and
      anomalous dispersion regimes, even though fourth-order dispersion and the fifth
      order nonlinear effects are not taken into account.

PMID- 24922432
TI  - Phase retrieval applied to stellar occultation for asteroid silhouette
      characterization.
AB  - Here we expand on the current methods of characterizing small astronomical
      bodies, particularly asteroids, by viewing stellar occultation events. Stellar
      occultation has proven to be a viable method for determining the size of moons
      and asteroids; however, it comes with some limitations. In general the method
      does not consider or use all of the known diffraction effects that occur and thus
      provides a nominal radius--not a shape--of the occluder. We show that most
      stellar occultation events involving small near-Earth asteroids occur with low
      Fresnel numbers. This in effect renders the traditional methods useless to
      characterize the shape, because no sharp shadow exists. We show that using
      similar data collection to that of the traditional occultation method and
      inverting a Fresnel diffraction equation by a phase retrieval process can yield a
      complete reconstruction of the silhouette of the occluder. The effect of noise in
      the measurements is also discussed. A practical example applied to the asteroid
      25143 Itokawa is shown.

PMID- 24922433
TI  - Homodyne interferometry with quadrature fringe detection for absolute gravimeter.
AB  - An absolute gravimeter is based on interferometric displacement measurement
      during repeated free falls of a target mirror in a high vacuum. A suitable
      homodyne quadrature laser interferometer is developed and reported. Standard
      deviation of the mean absolute gravity value in a typical two-day measurement
      session is less than 1*10-8 m/s2. Additionally, digital demodulation of the
      interference signal using a 90 degrees  phase-shift filter based on the Hilbert
      transform is presented. A combination of optical and digital quadrature phase
      shifts is shown to be helpful to improve accuracy in homodyne interferometers
      with the accelerated target mirror.

PMID- 24922434
TI  - Frame frequency prediction for Risley-prism-based imaging laser radar.
AB  - A dual-wedge scanner has potential applications in laser imaging radar. To
      realize fast scanning imaging without a blind region, the rotation rates of the
      wedges have to be controlled to perform beam scanning along appropriate track
      paths. The first-order paraxial approximation method is employed to investigate
      the 2D scan patterns and path density for different angular frequency ratios of
      the wedges rotating steadily in the same and opposite directions. The frame rate
      of no-blind-region scanning imaging is estimated in terms of the imaging coverage
      requirement. The internal relations between the rotation rates, the instantaneous
      field of view (IFOV), and the imaging velocity are revealed. The results show
      that the spiral scanning trace, resulting from co-rotating wedges, is dense in
      the center and sparse at the edge of the scanning field. The reverse results can
      be obtained for the rosette scanning trace, resulting from counter-rotating
      wedges. The denser the scanning trace is, the longer the scan period is. The
      faster the wedges rotate and the wider the IFOV is, the higher the frame rate is.
      When the ratio of the width of IFOV to the angular radius of the scanning field
      is 0.15, the frame rate of no-blind-region spiral scanning imaging can be up to
      18 fps for wedge rotation rate of 12000  r/min, and that for rosette scanning
      imaging can be up to 20 fps.

PMID- 24922435
TI  - Large-area irradiance-mode spectral response measurements of solar cells by a
      light-emitting, diode-based integrating sphere source.
AB  - An irradiance-mode absolute differential spectral response (SR) measurement
      system based on a light emitting diode (LED) array is described. The LEDs are
      coupled to an integrating sphere whose output irradiance is uniform to better
      than 2% over an area of 160 mm by 160 mm. SR measurements of solar cells when
      subject to diffuse irradiation, as provided by the integrating sphere, are
      compared with collimated irradiance SR measurements. Issues originating from the
      differences in angular response of the reference versus the test cells are also
      investigated. The SR curves of large-area cells with dimensions of up to 155 mm
      are measured and then used to calculate the cell's short circuit current (I(sc)),
      if illuminated by a defined solar spectrum. The resulting values of I(sc) agree
      well with the values obtained from secondary measurements.

PMID- 24922436
TI  - Development of an all-optical temperature insensitive nonpendulum-type tilt
      sensor employing fiber Bragg gratings.
AB  - A design strategy for the development of an all-optical, temperature insensitive,
      nonpendulum-type tilt sensor employing fiber Bragg gratings (FBGs) is proposed
      and experimentally demonstrated. Being nonpendulum-type, there is no possibility
      of any inherent friction and the limiting effects at mechanical joints. The
      sensor is observed to be capable of measuring magnitude, as well as the direction
      of inclination from horizontal strategically more effectively and without any
      inherent instability. This is reflected in a relatively better resolution (better
      than 0.004 degrees ), a better accuracy (~+/-0.05 degrees ), and a lesser maximum
      discrepancy (~+/-0.001  nm) during the forward as well as the reverse tilt.
      Sensitivity of the proposed sensor, theoretically proportional to the half of the
      mass employed in the sensor design, is observed to be 0.012  nm/ degrees  with a
      comparatively smaller mass. Importantly, sensor response is characterized by a
      very high degree of reversibility and repeatability over the designed/observed
      dynamic range.

PMID- 24922437
TI  - Photonic crystal fiber based dual-wavelength Q-switched fiber laser using
      graphene oxide as a saturable absorber.
AB  - A Q-switched dual-wavelength fiber laser with narrow channel spacing is proposed
      and demonstrated. The fiber laser is built around a 3 m long erbium doped fiber
      as the gain medium and a 10 cm long photonic crystal fiber (PCF) as the element
      used to generate the dual-wavelength output. The PCF has a solid core
      approximately 4.37 MUm in diameter and is surrounded by microscopic air-holes
      with a diameter of about 5.06 MUm each as well as a zero-dispersion wavelength of
      about 980 nm. A graphene oxide based saturable absorber is used to generate the
      desired pulsed output. At the maximum pump power of 72 mW the laser is capable of
      generating pulses with a repetition rate and pulse-width of 31.0 kHz and 7.0 MUs,
      respectively, as well as an average output power and pulse energy of 0.086 mW and
      2.8 nJ, respectively. The proposed fiber laser has substantial potential for use
      in applications that require longer duration pulsed outputs such as in range
      finding and terahertz radiation generation.

PMID- 24922438
TI  - Standards for ultrashort-laser-pulse-measurement techniques and their
      consideration for self-referenced spectral interferometry.
AB  - Issues important for new ultrashort-pulse-measurement techniques include the
      generation of theoretical example traces for common pulses, validity ranges,
      ambiguities, coherent artifacts, device calibration sensitivity, iterative
      retrieval convergence, and feedback regarding measurement accuracy.
      Unfortunately, in the past, such issues have gone unconsidered, yielding long
      histories of unsatisfactory measurements. We review these issues here in the hope
      that future proposers of new techniques will consider them without delay, and, as
      an example, we address them for a relatively new technique: self-referenced
      spectral interferometry. 

PMID- 24922439
TI  - Modeling of multiple-optical-axis pattern-integrated interference lithography
      systems.
AB  - The image quality and collimation in a multiple-optical-axis pattern-integrated
      interference lithography system are evaluated for an elementary optical system
      composed of single-element lenses. Image quality and collimation are individually
      and jointly optimized for these lenses. Example images for a jointly optimized
      system are simulated using a combination of ray tracing and Fourier analysis.
      Even with these nonoptimized components, reasonable fidelity is shown to be
      possible. 

PMID- 24922440
TI  - Composition optimization of scintillating rare-earth nanocrystals in oxide glass
      ceramics for radiation spectroscopy.
AB  - Glass-ceramic nanocomposites comprising GdBr3/CeBr3 loaded sodium-aluminosilicate
      glasses in which scintillating crystallites are precipitated in situ from a host
      glass matrix were studied. This materials system shows promise as an alternative
      to single-crystal scintillators, with potential to be fabricated into a wide
      variety of sizes, shapes, and compositions. Batch compositions containing 15-18
      mol. % GdBr3 and 3-4 mol. % CeBr3 were prepared and analyzed for photoluminescent
      light yield. Light yield peaked with rare-earth content of 15 mol. % GdBr3 and 4
      mol. % CeBr3. Preliminary ceramization studies on this composition found that the
      precipitated phase more closely matched a Gd2O3-CeO2 mixture rather than the
      GdBr3(Ce) that was targeted.

PMID- 24922441
TI  - Multifilter phase imaging with partially coherent light.
AB  - A novel quantitative phase imaging method is shown to estimate phase accurately
      over a wide range of length scales using Kohler illumination from an extended
      incoherent source. The method is based on estimating the longitudinal intensity
      derivative in the transport-of-intensity equation via convolution with multiple
      Savitzky-Golay differentiation filters and generalizes methods previously
      developed for coherent imaging to the practical scenario of partially coherent
      imaging. The resulting noise and resolution performance are evaluated via
      numerical simulation and demonstrated experimentally using a blazed transmission
      grating as well as a single-mode fiber as test objects. 

PMID- 24922442
TI  - Infrared lidar observations of stratospheric aerosols.
AB  - We observed the stratospheric aerosol layer at 34 degrees  north latitude with a
      photon-counting 1574 nm lidar on three occasions in 2011. During all of the
      observations, we also operated a nearby 523.5 nm micropulse lidar and acquired
      National Weather Service upper air data. We analyzed the lidar data to find
      scattering ratio profiles and the integrated aerosol backscatter at both
      wavelengths and then calculated the color ratio and wavelength exponent for lidar
      backscattering from the stratospheric aerosols. The visible-light integrated
      backscatter values of the layer were in the range 2.8-3.5*10-4 sr-1 and the
      infrared integrated backscatter values ranged from 2.4 to 3.7*10-5  sr-1. The
      wavelength exponent was determined to be 1.9+/-0.2.

PMID- 24922443
TI  - Size- and support-dependent evolution of the oxidation state and structure by
      oxidation of subnanometer cobalt clusters.
AB  - Size-selected subnanometer cobalt clusters with 4, 7, and 27 cobalt atoms
      supported on amorphous alumina and ultrananocrystalline diamond (UNCD) surfaces
      were oxidized after exposure to ambient air. Grazing incidence X-ray absorption
      near-edge spectroscopy (GIXANES) and near-edge X-ray absorption fine structure
      (NEXAFS) were used to characterize the clusters revealed a strong dependency of
      the oxidation state and structure of the clusters on the surface. A dominant
      Co(2+) phase was identified in all samples. However, XANES analysis of cobalt
      clusters on UNCD showed that ~10% fraction of a Co(0) phase was identified for
      all three cluster sizes and about 30 and 12% fraction of a Co(3+) phase in 4, 7,
      and 27 atom clusters, respectively. In the alumina-supported clusters, the
      dominating Co(2+) component was attributed to a cobalt aluminate, indicative of a
      very strong binding to the support. NEXAFS showed that in addition to strong
      binding of the clusters to alumina, their structure to a great extent follows the
      tetrahedral morphology of the support. All supported clusters were found to be
      resistant to agglomeration when exposed to reactive gases at elevated
      temperatures and atmospheric pressure. 

PMID- 24922444
TI  - Effect of disease stage on progression of hydroxychloroquine retinopathy.
AB  - IMPORTANCE: Hydroxychloroquine sulfate retinopathy can progress after the drug is
      stopped. It is not clear how this relates to the stage of retinopathy or whether
      early screening with modern imaging technology can prevent progression and visual
      loss. OBJECTIVE: To determine the relationship between progression of retinopathy
      and the severity of disease using objective data from optical coherence
      tomography and assess the value of early screening for the toxic effects of
      hydroxychloroquine. DESIGN, SETTING, AND PARTICIPANTS: Clinical findings in
      patients with hydroxychloroquine retinopathy were monitored with repeated
      anatomical and functional examinations for 13 to 40 months after the drug was
      stopped in a referral practice in a university medical center. Eleven patients
      participated, with the severity of toxic effects categorized as early (patchy
      parafoveal damage shown on field or objective testing), moderate (a 50%-100%
      parafoveal ring of optical coherence tomography thinning but intact retinal
      pigment epithelium), and severe (visible bull's-eye damage). MAIN OUTCOMES AND
      MEASURES: Visual acuity, white 10-2 visual field pattern density plots, fundus
      autofluorescence, spectral-density optical coherence tomography cross sections,
      thickness (from cube diagrams), and ellipsoid zone length. RESULTS: Visual acuity
      and visual fields showed no consistent change. Fundus autofluorescence showed
      little or no change except in severe cases in which the bull's-eye damage
      expanded progressively. Optical coherence tomography cross sections showed little
      visible change in early and moderate cases but progressive foveal thinning
      (approximately 7 MUm/y) and loss of ellipsoid zone (in the range of 100 MUm/y) in
      severe cases, which was confirmed by quantitative measurements. The measurements
      also showed some foveal thinning (approximately 4 MUm/y) and deepening of
      parafoveal loss in moderate cases, but the breadth of the ellipsoid zone remained
      constant in both early and moderate cases. A few cases showed a suggestion of
      ellipsoid zone improvement. CONCLUSIONS AND RELEVANCE: Patients with
      hydroxychloroquine retinopathy involving the retinal pigment epithelium
      demonstrated progressive damage on optical coherence tomography for at least 3
      years after the drug was discontinued, including loss of foveal thickness and
      cone structure. Cases recognized before retinal pigment epithelium damage
      retained foveal architecture with little retinal thinning. Early recognition of
      hydroxychloroquine toxic effects before any fundus changes are visible, using
      visual fields and optical coherence tomography (along with fundus
      autofluorescence and multifocal electroretinography as indicated), will greatly
      minimize late progression and the risk of visual loss.

PMID- 24922445
TI  - [What is your diagnosis? A "fat arm". Onchocerciasis].
AB  - We report a case of edema of the right forearm with pruriginous papules and
      eosinophilia in the blood. The patient had lived in a forested area of Cameroon.
      The clinical, laboratory, and geographical findings led to a diagnosis of
      onchocerciasis, despite the absence of microfilaments on skin biopsy samples. The
      patient was successfully treated with ivermectin and doxycycline. 

PMID- 24922446
TI  - [Evidence in rehabilitation on pneumological diseases: COPD and asthma
      bronchiale].

PMID- 24922447
TI  - [Rehabilitation after acute myocardial infarction].

PMID- 24922448
TI  - [Letter from a reader].

PMID- 24922449
TI  - [Reply].

PMID- 24922450
TI  - [The implementation of the ICF into REHADAT's information system].

PMID- 24922451
TI  - Use of metallomics and metabolomics to assess metal pollution in Donana National
      Park (SW Spain).
AB  - Monitoring organism exposure to heavy metals has acquired increased importance in
      the last decades. The mouse Mus spretus has been used to assess the biological
      response to contaminants in the relevant ecological area of Donana National Park
      (DNP) and surrounding areas (SW Spain), where many migrating birds land for
      breeding and feeding every year. A metallomics approach, based on the
      characterization of metal biomolecules using size exclusion chromatography
      coupled with inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and a
      metabolomics approach based on direct infusion to a mass spectrometer (DI-ESI
      QTOF-MS) followed by a partial linear square-discriminant analysis (PLS-DA), were
      used to compare the biological responses of M. spretus living in three areas of
      DNP (the reference) and surrounding areas (El Partido and El Matochal). The
      activities of key antioxidant enzymes, such as Cu/Zn-SOD, Mn-SOD, CAT, GR, and
      guaiacol peroxidase, were also determined in connection with environmental
      contamination issues. The results show differences caused by the presence of
      metals in the ecosystem that affected to the levels of metals and
      metalloproteins, such as MT, Cu/Zn-SOD, or Mn-CA, the breakdown of membrane
      phospholipids, perturbations in metabolic pathways, related to energy metabolism,
      and oxidative stress. 

PMID- 24922452
TI  - Preliminary evaluation of a personal healthcare system prototype for cognitive
      eRehabilitation in a living assistance domain.
AB  - The integration of rehabilitation systems in an ambient assisted living
      environment can provide a powerful and versatile tool for long-term stroke
      rehabilitation goals. This paper introduces a novel concept of a personalized
      cognitive rehabilitation system in a naturalistic setting. The proposed platform
      was developed within the CogWatch project, with the intent of fostering
      independence in activities of daily living in patients with apraxia and action
      disorganization syndrome. Technical usability was evaluated in a series of pilot
      experiments, which illustrate how this approach may help to retrain patients in
      activities of daily living. The first system prototype has been tested with 36
      participants divided into three groups, providing an exploratory evaluation of
      the usability of this solution and its acceptability. The technical solutions
      used within the CogWatch project are targeted to meet both the end users' needs
      from the interaction and usability point of views and the clinical requirements
      associated with the use of such systems. The challenges behind the development of
      ambient assisted living systems for cognitive rehabilitation are discussed. 

PMID- 24922453
TI  - Normalized GNSS interference pattern technique for altimetry.
AB  - It is well known that reflected signals from Global Navigation Satellite Systems
      (GNSS) can be used for altimetry applications, such as monitoring of water levels
      and determining snow height. Due to the interference of these reflected signals
      and the motion of satellites in space, the signal-to-noise ratio (SNR) measured
      at the receiver slowly oscillates. The oscillation rate is proportional to the
      change in the propagation path difference between the direct and reflected
      signals, which depends on the satellite elevation angle. Assuming a known
      receiver position, it is possible to compute the distance between the antenna and
      the surface of reflection from the measured oscillation rate. This technique is
      usually known as the interference pattern technique (IPT). In this paper, we
      propose to normalize the measurements in order to derive an alternative model of
      the SNR variations. From this model, we define a maximum likelihood estimate of
      the antenna height that reduces the estimation time to a fraction of one period
      of the SNR variation. We also derive the Cramer-Rao lower bound for the IPT and
      use it to assess the sensitivity of different parameters to the estimation of the
      antenna height. Finally, we propose an experimental framework, and we use it to
      assess our approach with real GPS L1 C/A signals. 

PMID- 24922454
TI  - Augmented GNSS differential corrections minimum mean square error estimation
      sensitivity to spatial correlation modeling errors.
AB  - Railway signaling is a safety system that has evolved over the last couple of
      centuries towards autonomous functionality. Recently, great effort is being
      devoted in this field, towards the use and exploitation of Global Navigation
      Satellite System (GNSS) signals and GNSS augmentation systems in view of lower
      railway track equipments and maintenance costs, that is a priority to sustain the
      investments for modernizing the local and regional lines most of which lack
      automatic train protection systems and are still manually operated. The objective
      of this paper is to assess the sensitivity of the Linear Minimum Mean Square
      Error (LMMSE) algorithm to modeling errors in the spatial correlation function
      that characterizes true pseudorange Differential Corrections (DCs). This study is
      inspired by the railway application; however, it applies to all transportation
      systems, including the road sector, that need to be complemented by an
      augmentation system in order to deliver accurate and reliable positioning with
      integrity specifications. A vector of noisy pseudorange DC measurements are
      simulated, assuming a Gauss-Markov model with a decay rate parameter inversely
      proportional to the correlation distance that exists between two points of a
      certain environment. The LMMSE algorithm is applied on this vector to estimate
      the true DC, and the estimation error is compared to the noise added during
      simulation. The results show that for large enough correlation distance to
      Reference Stations (RSs) distance separation ratio values, the LMMSE brings
      considerable advantage in terms of estimation error accuracy and precision.
      Conversely, the LMMSE algorithm may deteriorate the quality of the DC
      measurements whenever the ratio falls below a certain threshold. 

PMID- 24922455
TI  - Innovative pressure sensor platform and its integration with an end-user
      application.
AB  - This paper describes the fully integration of an innovative and low-cost pressure
      sensor sheet based on a bendable and printed electronics technology. All
      integration stages are covered, from most low-level functional system, like
      physical analog sensor data acquisition, followed by embedded data processing, to
      end user interactive visual application. Data acquisition embedded software and
      hardware was developed using a Rapid Control Prototyping (RCP). Finally, after
      first electronic prototype successful testing, a Taylor-made electronics was
      developed, reducing electronics volume to 3.5 cm * 6 cm * 2 cm with a maximum
      power consumption of 765 mW for both electronics and pressure sensor sheet.

PMID- 24922456
TI  - The design, fabrication and characterization of a transparent atom chip.
AB  - This study describes the design and fabrication of transparent atom chips for
      atomic physics experiments. A fabrication process was developed to define the
      wire patterns on a transparent glass substrate to create the desired magnetic
      field for atom trapping experiments. An area on the chip was reserved for the
      optical access, so that the laser light can penetrate directly through the glass
      substrate for the laser cooling process. Furthermore, since the thermal
      conductivity of the glass substrate is poorer than other common materials for
      atom chip substrate, for example silicon, silicon carbide, aluminum nitride.
      Thus, heat dissipation copper blocks are designed on the front and back of the
      glass substrate to improve the electrical current conduction. The testing results
      showed that a maximum burnout current of 2 A was measured from the wire pattern
      (with a width of 100 MUm and a height of 20 MUm) without any heat dissipation
      design and it can increase to 2.5 A with a heat dissipation design on the front
      side of the atom chips. Therefore, heat dissipation copper blocks were designed
      and fabricated on the back of the glass substrate just under the wire patterns
      which increases the maximum burnout current to 4.5 A. Moreover, a maximum burnout
      current of 6 A was achieved when the entire backside glass substrate was recessed
      and a thicker copper block was electroplated, which meets most requirements of
      atomic physics experiments. 

PMID- 24922457
TI  - A comprehensive study on technologies of tyre monitoring systems and possible
      energy solutions.
AB  - This article presents an overview on the state of the art of Tyre Pressure
      Monitoring System related technologies. This includes examining the latest
      pressure sensing methods and comparing different types of pressure transducers,
      particularly their power consumption and measuring range. Having the aim of this
      research to investigate possible means to obtain a tyre condition monitoring
      system (TCMS) powered by energy harvesting, various approaches of energy
      harvesting techniques were evaluated to determine which approach is the most
      applicable for generating energy within the pneumatic tyre domain and under
      rolling tyre dynamic conditions. This article starts with an historical review of
      pneumatic tyre development and demonstrates the reasons and explains the need for
      using a tyre condition monitoring system. Following this, different tyre pressure
      measurement approaches are compared in order to determine what type of pressure
      sensor is best to consider in the research proposal plan. Then possible energy
      harvesting means inside land vehicle pneumatic tyres are reviewed. Following
      this, state of the art battery-less tyre pressure monitoring systems developed by
      individual researchers or by world leading tyre manufacturers are presented.
      Finally conclusions are drawn based on the reviewed documents cited in this
      article and a research proposal plan is presented. 

PMID- 24922458
TI  - Left ventricular strain and its pattern estimated from cine CMR and validation
      with DENSE.
AB  - Measurement of local strain provides insight into the biomechanical significance
      of viable myocardium. We attempted to estimate myocardial strain from cine
      cardiovascular magnetic resonance (CMR) images by using a b-spline deformable
      image registration method. Three healthy volunteers and 41 patients with either
      recent or chronic myocardial infarction (MI) were studied at 1.5 Tesla with both
      cine and DENSE CMR. Regional circumferential and radial left ventricular strains
      were estimated from cine and DENSE acquisitions. In all healthy volunteers, there
      was no difference for peak circumferential strain (- 0.18 +/- 0.04 versus - 0.18
      +/- 0.03, p = 0.76) between cine and DENSE CMR, however peak radial strain was
      overestimated from cine (0.84 +/- 0.37 versus 0.49 +/- 0.2, p < 0.01). In the
      patient study, the peak strain patterns predicted by cine were similar to the
      patterns from DENSE, including the strain evolution related to recovery time and
      strain patterns related to MI scar extent. Furthermore, cine-derived strain
      disclosed different strain patterns in MI and non-MI regions, and regions with
      transmural and non-transmural MI as DENSE. Although there were large variations
      with radial strain measurements from cine CMR images, useful circumferential
      strain information can be obtained from routine clinical CMR imaging. Cine strain
      analysis has potential to improve the diagnostic yield from routine CMR imaging
      in clinical practice. 

PMID- 24922459
TI  - Survival is affected by mutation type and molecular mechanism in vascular Ehlers
      Danlos syndrome (EDS type IV).
AB  - PURPOSE: We sought to characterize the natural history of vascular Ehlers-Danlos
      syndrome in individuals with heterozygous COL3A1 mutations. METHODS: We reviewed
      clinical records for details of vascular, bowel, and organ complications in 1,231
      individuals (630 index cases and 601 relatives). RESULTS: Missense and splice
      site mutations accounted for more than 90% of the 572 alterations that we had
      identified in COL3A1. Median survival was 51 years but was influenced by gender
      (lower in men) and by the type of mutation. CONCLUSION: Although vascular Ehlers
      Danlos syndrome appears to be genetically homogeneous, allelic heterogeneity is
      marked, and the natural history varies with gender and type of mutation in
      COL3A1. These findings indicate that when counseling families, confirmation of
      the presence of a COL3A1 mutation and its nature can help evaluate the risks of
      complications. These data are also important ingredients in both the selection
      and allocation of individuals to appropriate arms in clinical trials to assess
      the effects of interventions.

PMID- 24922460
TI  - Differences in BRCA counseling and testing practices based on ordering provider
      type.
AB  - PURPOSE: The purpose of this study was to assess potential differences in genetic
      counseling services delivered by board-certified genetic health-care providers
      versus non-genetic health-care providers. We evaluated (i) patient recall and
      content of pretest genetic counseling for hereditary breast and ovarian cancer
      and (ii) whether full BRCA1 and 2 gene sequencing was performed when less
      expensive single-site or Ashkenazi Jewish founder mutation testing may have been
      sufficient. METHODS: Participants completed a questionnaire and provided BRCA
      test reports that included testing provider and type of test. Chi-square tests
      and logistic regression were used for analysis. RESULTS: Of 473 participants,
      >90% were white, female, and BRCA mutation carriers. Of the 276 (58%) with
      genetic health-care provider involvement, 97% recalled a pretest discussion as
      compared with 59% of those without genetic health-care provider involvement (P <
      0.001). Among the subgroup who recalled a pretest discussion (n = 385), those
      with genetic health-care provider involvement indicated higher adherence to eight
      recognized genetic counseling elements, four of which were statistically
      significant. Furthermore, involvement of a genetic health-care provider halved
      the likelihood that comprehensive BRCA testing was ordered among the 266 for whom
      single-site or multisite-3 testing may have been sufficient (P = 0.02).
      CONCLUSION: Our results suggest that genetic health-care provider involvement is
      associated with adherence to nationally recommended genetic counseling practices
      and could potentially reduce costs of BRCA genetic testing.

PMID- 24922461
TI  - Pregnancy-related deaths and complications in women with vascular Ehlers-Danlos
      syndrome.
AB  - PURPOSE: The purpose of this study was to characterize the nature and magnitude
      of pregnancy risks in women with vascular Ehlers-Danlos syndrome. METHODS:
      Pregnancy-related death rate was determined by a review of pedigrees of families
      with vascular Ehlers-Danlos syndrome. Maternal morbidity was characterized
      through semistructured interviews with women with vascular Ehlers-Danlos syndrome
      or their next of kin. RESULTS: Pregnancy-related deaths occurred in 30 of 565
      deliveries (5.3%). There was no difference in Kaplan-Meier survival curves
      between parous versus nulliparous women with vascular Ehlers-Danlos syndrome.
      Interviews with 39 women indicated that 46% of deliveries were uncomplicated. The
      most common pregnancy-related complications were third-/fourth-degree lacerations
      (20%) and preterm delivery (19%). Life-threatening complications occurred in
      14.5% of deliveries and included arterial dissection/rupture (9.2%), uterine
      rupture (2.6%), and surgical complications (2.6%). There were 5 maternal deaths
      in 76 deliveries (6.5%). CONCLUSION: The risk of pregnancy-related complications
      is increased in women with vascular Ehlers-Danlos syndrome compared with the
      general population; however, survival data indicate that pregnancy does not
      appear to affect overall mortality compared with nulliparous women with vascular
      Ehlers-Danlos syndrome. The data were insufficient to determine whether mode or
      timing of delivery influenced risk of complications. Women with vascular Ehlers
      Danlos syndrome should be engaged in a shared decision-making process when
      contemplating pregnancy and pregnancy management.

PMID- 24922462
TI  - Effectiveness of the buccal mucosa route for methadone administration at the end
      of life.
AB  - BACKGROUND: Methadone is a useful analgesic for neuropathic and nociceptive pain.
      However, there is little information about the use of methadone in the final days
      of life when a patient cannot swallow, discouraging its use by many palliative
      care physicians. OBJECTIVE: The purpose of this study was to investigate the
      effectiveness of switching patients on oral methadone at the end of life to
      methadone by the buccal mucosa route. METHODS: This is a case series comprising
      36 patients on the Toronto Grace Palliative Care Unit (PCU) who took methadone
      between 2010 and 2012. Their health records were retrospectively reviewed. When
      patients could no longer swallow at the end of life, oral methadone was replaced
      with methadone solution in a concentration of 10 mg/mL, placed in the space
      between the buccal mucosa and lower molars. RESULTS: Twenty-five patients met
      inclusion criteria for the series. Twenty-four (96%) of the patients tolerated
      methadone by the buccal route and were able to continue receiving it that way
      until they died. Methadone was discontinued by the buccal route in one case (4%)
      because of intolerance to having medication placed in the oral cavity. Of the
      patients who remained on buccal methadone, there was a need to increase the dose
      in two patients with the remaining patients taking the same dose of buccal
      methadone until they died. CONCLUSION: The cases reviewed suggest that methadone
      is well tolerated and effective when switched to the buccal route in patients at
      the end of life on a palliative care unit.

PMID- 24922463
TI  - A low cytotoxic cationic metal-organic framework carrier for controllable drug
      release.
AB  - A positively charged porous drug carrier MOF-74-Fe(III) (1, MOF = metal-organic
      framework), which could not be directly synthesized using ferric salts, was
      prepared through the oxidation of the neutral crystal MOF-74-Fe(II). This
      cationic host material exhibits very low cytotoxicity upon PC12 cells by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and high drug loading
      capacity of ibuprofen anions (~15.9 wt %) through ion exchange and salt
      penetration procedures. Controlled by anion exchange, two mechanisms were
      involved in the drug release process with different drug delivery rates due to
      the presence of coordinated or free ibuprofen anions, making the administration
      of drug release more flexible.

PMID- 24922464
TI  - Combination of optical and electrical loss analyses for a Si-phthalocyanine dye
      sensitized solar cell.
AB  - In order to promote the development of solar cells with varying types of
      sensitizers including dyes and quantum dots, it is crucial to establish a general
      experimental analysis that accounts for all important optical and electrical
      losses resulting from interfacial phenomena. All of these varying types of solar
      cells share common features where a mesoporous scaffold is used as a sensitizer
      loading support as well as an electron transport material, which may result in
      light scattering. The loss of efficiency at interfaces of the sensitizer, the
      mesoporous TiO2 nanoparticle films, the FTO conductive layer, and the supportive
      glass substrate should be considered in addition to the photoinduced electron
      transport properties within a cell. On the basis of optical parameters, one can
      obtain the internal quantum efficiency (IQE) of a solar cell, an important
      parameter that cannot be directly measured but must be derived from several key
      experiments. By integrating an optical loss model with an electrical loss model,
      many solar cell parameters could be characterized from electro-optical
      observables including reflectance, transmittance, and absorptance of the dye
      sensitizer, the electron injection efficiency, and the charge collection
      efficiency. In this work, an integrated electro-optical approach has been applied
      to SiPc (Pc 61) dye-sensitized solar cells for evaluating the parameters
      affecting the overall power conversion efficiency. The absorptance results of the
      Pc 61 dye-sensitized solar cell provide evidence that the adsorbed Pc 61 forms
      noninjection layers on TiO2 surfaces when the dye immersion time exceeds 120 min,
      resulting in shading light from the active layer rather than an increase in
      photoelectric current efficiency. 

PMID- 24922465
TI  - [Not Available].

PMID- 24922466
TI  - Usage of benzodiazepines: A review.
AB  - Abstract Purpose. The use of benzodiazepines remains a source of controversy.
      Some prescribers believe that they are beneficial and espouse their use; others
      regard their risk:benefit ratio as too adverse for any but occasional use. This
      review considers these viewpoints based on the appropriate literature. Survey.
      The recent English-language literature relating to this topic was surveyed. The
      publications proved too heterogeneous for a formal meta-analysis, so a
      descriptive review is provided. Overview. Surveys of benzodiazepine use provide
      data mainly from the UK, Europe and North America. Prescribing patterns varied
      widely but long-term usage is common and sometimes the norm. Conclusions. Long
      term prescription of benzodiazepines still takes place despite general warnings
      from the medical and other professions and drug regulatory bodies that long-term
      use is unjustified both from the lack of a systemic database establishing such
      efficacy and a large literature documenting the risks of long-term usage, such as
      dependence. The young and the old are particularly at risk. Continued monitoring
      is essential, but the regulatory authorities may need to take a more active role
      in curbing such undesirable practice. 

PMID- 24922467
TI  - Suicidal and violent behaviour in mood disorders: A major public health problem.
      A review for the clinician.
AB  - Abstract Suicide attempt, and particularly completed suicide are relatively rare
      events in the community, but they are very common among psychiatric patients.
      Since over 90% of suicide victims suffer from (mostly untreated) current major
      mental disorders (particularly from major depressive episode), psychiatric risk
      factors are the clinically most useful predictors, especially if psychosocial and
      demographic risk factors are also pesent. Violent behaviours associated with mood
      disorders constitute a related yet independently also important aspect of this
      illness, and assessment and management of violence is a key component of everyday
      psychiatric practice. While most people with current mental disorder are not
      violent, violence is more common among seriously mentally ill individuals than in
      healthy persons. This is particularly true for untreated schizophrenics and
      untreated patients with major mood disorders, first of all in the cases of
      comorbid substance use disorders, mainly among those with current mania or
      postpartum depression. Although specific clinical studies are lacking, it is very
      lilely that successful acute and long-tem treatment of mood disorders can reduce
      the risk of violent behaviour in this patient population. 

PMID- 24922468
TI  - Time patterns of inpatient suicides.
AB  - Abstract Objective. Time patterns of suicides have been investigated in many
      population-based studies, but there are no studies exploring time patterns of
      suicides during psychiatric inpatient stay up to now. Methods. All inpatient
      suicides (1998-2007) of a psychiatric university hospital were identified by the
      German psychiatric basic documentation system (DGPPNBADO). Descriptive and
      univariate analyses were performed to analyse time patterns of inpatient
      suicides. Results. No significant differences could be found for the occurrence
      of the 37 inpatient suicides due to season (chi(2)=1.595, P=0.696), month
      (chi(2)=4.838, P=0.958) or weekday (chi(2)=5.189, P=0.550) of suicide.
      Furthermore, we could not find an unequal distribution of suicides due to month
      of birth (chi(2)=12.622, P=0.337). 78.4% of inpatient suicides occurred within 50
      days after admission. Fourteen inpatients committed suicide around public
      holidays, two around their birthday. Conclusions. Apart from a notably enhanced
      risk of suicide in the period after admission, we could not find any time
      patterns to be of high relevance to inpatient suicides. There may be more
      relevant risk factors than cyclic or temporal variations. 

PMID- 24922469
TI  - Barriers of antenatal folate-supplementation: The role of depression and trait
      anxiety on periconceptional folate-intake.
AB  - Abstract Objective. The aim of the research was to reveal the effect of antenatal
      depressive symptoms and trait-anxiety on folate supplementation. Higher levels of
      depression, and trait-anxiety were hypothesized to be associated with
      insufficient folate intake among pregnant women in early pregnancy. Methods.
      Level of depressive symptoms, trait-anxiety, self-esteem, social capital, self
      related health, and demographic factors (age, number of siblings, marital,
      educational, employment, and socioeconomic-status) were established among 185
      Hungarian women in the first trimester of their pregnancies. Depressive symptoms
      and trait-anxiety were evaluated with the Short Hungarian Version of the Beck
      Depression Inventory and the Hungarian version of the Spielberger State-Trait
      Anxiety Inventory form Y (STAI-Y). Results. The higher levels of both trait
      anxiety and self-esteem decreased the folate-intake significantly, OR=0.925
      (95%CI=0.863-0.991; P=0.026) and OR=0.897 (95%CI=0.808-0.996; P=0.041) while
      depressive symptoms did not have an effect on it. The lower level of education
      (less than 8 elementary years) had similar effects (OR=0.228 [95%CI=0.064-0.817],
      P=0,023). The lack of trust had a significant role too (P=0.043): those, who were
      distrustful with other people, also had a lower chance of supplementation
      (OR=0.620; 95%CI=0.390-0.986). Conclusions. The way to increase the openness
      towards folate-supplementation leads through the treatment of psychological
      disturbances and the restoration of social trust. 

PMID- 24922470
TI  - Incidence and risk for neutropenia/agranulocytosis among clozapine users: A
      retrospective cohort study.
AB  - Abstract Objective. To estimate the incidence and the risk of neutropenia or
      agranulocytosis (the outcome) associated with clozapine use (the exposure), and
      to identify risk factors. Methods. All data were derived from the computerized
      hospital database. Adult psychiatric patients were identified, and 95 incident
      clozapine users and 884 non-clozapine users were included. Cox proportional
      hazards regression was used to estimate the hazards ratio (HR) of developing the
      outcome after clozapine use adjusted for confounders. The interaction between
      clozapine and valproic acid was assessed a posteriori. Results. Throughout the 24
      month follow-up, the incidence of neutropenia was 6.3% in the clozapine group and
      5.8% in the non-clozapine group. One agranulocytosis was found in the non
      clozapine group. The HR (95% CI) for neutropenia were: clozapine 1.33 (0.54-3.25)
      and age . 45 years 2.99 (1.63-5.48). Lithium, as an independent protective
      factor, reduced the risk for neutropenia by 85% compared with patients who did
      not receive lithium, HR 0.15 (95% CI 0.02-1.09). Valproic acid might potentiate
      the clozapine-associated neutropenia (HR 5.10, 95% CI 0.70-37.12). Conclusion.
      Clozapine might slightly increase the risk of neutropenia in psychiatric
      patients. Concerning clozapine-associated neutropenia, older patients are at
      increased risk and use of valproic acid concurrently with clozapine should be
      avoided. 

PMID- 24922471
TI  - A prospective observational study of attention-deficit/hyperactivity disorder in
      Central and Eastern Europe and Turkey: Symptom severity and treatment options in
      a paediatric population.
AB  - Abstract Objective. This study investigates the relationship between treatment
      regimen, symptom severity, comorbidities and health outcomes of paediatric
      patients with attention-deficit/hyperactivity disorder (ADHD) in Central and
      Eastern Europe (CEE). Methods. Males and females aged 6-17 years with ADHD
      symptoms participated in this 12-month, prospective, observational, non
      randomised study. Symptoms and comorbidities were assessed using the Child and
      Adolescent Symptom Inventory-4 Parent Checklists (CSI-4; ASI-4, categories L/O),
      and the Clinical Global Impressions-ADHD-Severity scale (CGI-ADHD-S). Baseline
      data are presented. Results. The study included 566 patients from Czech Republic,
      Hungary, Romania, Slovakia and Turkey. Psychiatrists made all diagnoses using The
      American Psychiatric Association Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision (DSM-IV), World Health Organization
      International Statistical Classification of Diseases and Related Health Problems,
      10th Revision (ICD-10), and "other" criteria (73, 27 and 0.4%, respectively).
      Patients were grouped into two cohorts based on whether they were prescribed
      psycho- and/or pharmacotherapy (n=443) or not (n=123). Patients receiving
      prescribed treatment were older and demonstrated higher symptom severity scores
      than those receiving no or "other" treatment. Most patients were prescribed
      conventional treatment for ADHD at baseline. Conclusions. Continued assessment of
      this population may aid the treatment and outcomes of ADHD in CEE. 

PMID- 24922472
TI  - Borderline personality and emotional reactivity to theoretical media events: A
      pilot study.
AB  - Abstract Objective. The purpose of this study was to determine if patients with
      borderline personality emotionally react any differently than controls to
      theoretical media events of different valences. Methods. In this cross-sectional
      sample of convenience, we examined among 70 primary care patients the
      relationship between borderline personality disorder, according to two diagnostic
      measures (the borderline personality scale of the Personality Diagnostic
      Questionaire-4 and the Self-Harm Inventory), and emotional reactions to three
      types of theoretical media events - positive, negative, and neutral events.
      Results. Participants with versus without borderline personality evidenced no
      emotional differences to the various media events according to the Personality
      Diagnostic Questionnaire-4. However, according to the Self-Harm Inventory,
      participants with borderline personality symptomatology were more likely to rate
      neutral events with greater emotional intensity, but not positive or negative
      events. Conclusions. These findings suggest that patients with borderline
      personality may tend to respond more dramatically to ambiguous stimuli, such as
      neutral environmental events. We discuss the potential implications of these
      findings. 

PMID- 24922473
TI  - Prophylactic continuous administration of landiolol, a novel beta1 blocker,
      blunts hyperdynamic responses during electroconvulsive therapy without altering
      seizure activity.
AB  - Abstract Objective. In previous reports, it has been shown that many drugs may
      act against hyperdynamic responses during electro-convulsive therapy (ECT). The
      aim of this study was to conduct a randomized, placebo-controlled crossover study
      to investigate the hemodynamic responses and seizure duration during ECT by
      continuous administration of two doses of landiolol, a novel short-acting beta1
      adrenergic blocker, including standard and high-dose. Methods. Thirty-two
      patients undergoing ECT participated in this study. The control treatment was
      infusion of saline alone. The standard-dose of landiolol, 0.125 mg/kg per min,
      was infused over a 1-min period as a standard treatment. The high-dose landiolol
      treatment was 0.25 mg/kg per min, also infused over a 1-min period. After
      landiolol treatments, patients received landiolol at 0.04 mg/kg per min. Propofol
      and succinylcholine was then administered, and electrical stimulation was
      applied. Results. Both peak heart rate and mean arterial pressure after ECT was
      lowest with high-dose landiolol treatment. Motor and EEG seizure duration did not
      differ among the treatments. Conclusion. The results of this study show that high
      dose landiolol treatment blunts hyperdynamic responses during ECT. Furthermore,
      landiolol does not reduce the seizure duration. 

PMID- 24922474
TI  - Outcomes of the Chinese Basic Conversation Skill Module (CBCSM) for people with
      schizophrenia having mild to moderate symptoms and dysfunction in Hong Kong.
AB  - Abstract This study tested the effectiveness of a culturally adapted Chinese
      Basic Conversation Skill Module (CBCSM) for Hong Kong Chinese with schizophrenia.
      A total of 106 participants with schizophrenia who had mild to moderate levels of
      symptoms and dysfunction were recruited between January 2004 and September 2005.
      After random allocation, 35 participants were assigned to the CBCSM group with
      skill generalization training (SGT), 35 participants were assigned to the CBCSM
      group without SGT, and 36 participants were assigned to the placebo group. All
      participants were assessed by a blind rater at baseline, 5 weeks after
      commencement of skills training, and 3 and 6 months after completion of skills
      training on conversation skill mastery, subjective personal well being, and self
      esteem. After 15 sessions of intervention, the CBCSM group with SGT and the CBCSM
      group outperformed the placebo group in social skills. At the 6-month follow-up,
      social skill of CBCSM group with SGT was better than the CBCSM group and the
      placebo group. CBCSM with SGT was found to be effective in improving conversation
      skill of people with schizophrenia in Hong Kong. This combined strategy was also
      shown to be better than mere application of CBCSM in helping conversation skill
      mastery. 

PMID- 24922475
TI  - Validation of the Symptom Checklist SCL-27 in psychiatric patients: Psychometric
      testing of a multidimensional short form.
AB  - Abstract SCL-90-R, a multidimensional assessment instrument for mental health
      status, is among the most widely used instruments for the evaluation of therapies
      and quality management in mental institutions. With 90 items it is rather long
      and has a high redundancy as can be seen in its highly correlated scales. Thus
      many short versions have been constructed, among them the SCL-27, which was
      devised as a screening tool. It has 27 items, retains six of the nine SCL-90
      dimensions and has shown a good factor structure. So far it has only been
      validated in non-psychiatric samples. The aim of this study is to determine
      validity and other psychometric qualities of the SCL-27, compared to the SCL-90-R
      within a group of 449 psychiatric patients. The study found a large concordance
      between the symptom scales of the SCL-27 and the corresponding scales of the SCL
      90-R. The SCL-27 further showed good reliability and a sensitivity to change
      comparable to that of the 90-item version. A confirmatory factor analysis yields
      an acceptable factor validity which is better than that of the long version. This
      study concludes that the SCL-27 is suitable as a short assessment instrument for
      psychological health in psychiatric patients. 

PMID- 24922476
TI  - The utility of the Mood Disorders Questionnaire as a screening tool in a
      methadone maintenance treatment program.
AB  - Abstract Objective. Comorbid mental illness amongst methadone maintenance therapy
      clients may be common and screening may be warranted. The Mood Disorders
      Questionnaire (MDQ) is a screening tool for bipolar disorder that has been
      validated in other treatment settings. Its utility for patients with substance
      use disorders is assessed in this study. Methods. Clients of a methadone
      maintenance program were invited to complete the MDQ when they attended a public
      Drug and Alcohol Service for their regular scheduled appointments. Information
      about their history of substance use was also collected. Results. Eighty clients
      (43 females, 37 males) aged 35 +/- 8.0 years (mean +/- SD) participated in the
      study. Seventy-four clients completed the MDQ of which 36 (48.6%) obtained a
      positive screen. A check of client files suggested that only three of the 74
      participants had a current working diagnosis of bipolar disorder. These three
      participants had screened positive on the MDQ. Conclusions. There was a high
      prevalence of manic symptoms reported by participants, suggesting that screening
      for bipolar disorder in this population may be warranted. However, there is a
      risk of false positives with the MDQ, as it does not clearly differentiate
      between symptoms of mania and drug intoxication. 

PMID- 24922477
TI  - No association between genetic markers in BDNF gene and lithium prophylaxis in a
      Greek sample.
AB  - Abstract Lithium efficacy is, at least partially, under genetic control. We
      investigated the association between markers in BDNF and lithium prophylactic
      efficacy. A set of 10 SNPs within BDNF were genotyped in a sample of 83 bipolar
      patients. Response to lithium was assessed by presence or absence of any illness
      phases during a period of 3 years of longitudinal observation. No significant
      association was detected between the genetic variants tested in BDNF and lithium
      prophylaxis. Despite the negative association, limitations including small sample
      size suggest that larger scale genetic associations studies of these genes and
      lithium prophylaxis are nonetheless indicated. 

PMID- 24922478
TI  - Kissing or "osculation" in frontotemporal dementia.
AB  - The authors investigated the neuropsychiatry of kissing in frontotemporal
      dementia. Among 15 patients, two had compulsive social kissing, bitemporal
      involvement, and Kluver-Bucy symptoms, and four pursued kissing with sexually
      disinhibited behavior. Future research should clarify the neuropsychiatric
      significance of kissing behavior. 

PMID- 24922479
TI  - A chronic kidney disease risk score to determine tenofovir safety in a
      prospective cohort of HIV-positive male veterans.
AB  - OBJECTIVE: Tenofovir disoproxil fumarate is a widely used antiretroviral for HIV
      infection that has been associated with an increased risk of chronic kidney
      disease (CKD). Our objective was to derive a scoring system to predict 5-year
      risk of developing CKD in HIV-infected individuals and to estimate difference in
      risk associated with tenofovir use. DESIGN: We evaluated time to first occurrence
      of CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) in 21 590
      HIV-infected men from the Veterans Health Administration initiating
      antiretroviral therapy from 1997 to 2010. METHODS: We developed a point-based
      score using multivariable Cox regression models. Median follow-up was 6.3 years,
      during which 2059 CKD events occurred. RESULTS: Dominant contributors to the CKD
      risk score were traditional kidney risk factors (age, glucose, SBP, hypertension,
      triglycerides, proteinuria); CD4(+) cell count was also a component, but not HIV
      RNA. The overall 5-year event rate was 7.7% in tenofovir users and 3.8% in
      nonusers [overall adjusted hazard ratio 2.0, 95% confidence interval (CI) 1.8
      2.2]. There was a progressive increase in 5-year CKD risk, ranging from less than
      1% (zero points) to 16% (>=9 points) in nonusers of tenofovir, and from 1.4 to
      21.4% among tenofovir users. The estimated number-needed-to-harm (NNH) for
      tenofovir use ranged from 108 for those with zero points to 20 for persons with
      at least nine points. Among tenofovir users with at least 1 year exposure, NNH
      ranged from 68 (zero points) to five (>=9 points). CONCLUSION: The CKD risk score
      can be used to predict an HIV-infected individual's absolute risk of developing
      CKD over 5 years and may facilitate clinical decision-making around tenofovir
      use.

PMID- 24922481
TI  - Syphilis: an unusual cause of simultaneous aortic valve and ostial coronary
      artery disease.

PMID- 24922480
TI  - Rift valley Fever virus encephalitis is associated with an ineffective systemic
      immune response and activated T cell infiltration into the CNS in an
      immunocompetent mouse model.
AB  - BACKGROUND: Rift Valley fever virus (RVFV) causes outbreaks of severe disease in
      livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV
      generally causes a self-limiting febrile illness but in a subset of individuals,
      it progresses to more serious disease. One manifestation is a delayed-onset
      encephalitis that can be fatal or leave the afflicted with long-term neurologic
      sequelae. In order to design targeted interventions, the basic pathogenesis of
      RVFV encephalitis must be better understood. METHODOLOGY/PRINCIPAL FINDINGS: To
      characterize the host immune responses and viral kinetics associated with fatal
      and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs
      (DeltaNSs) that causes lethal disease only when administered intranasally (IN).
      Following IN infection, C57BL/6 mice developed severe neurologic disease and
      succumbed 7-9 days post-infection. In contrast, inoculation of DeltaNSs virus
      subcutaneously in the footpad (FP) resulted in a subclinical infection
      characterized by a robust immune response with rapid antibody production and
      strong T cell responses. IN-inoculated mice had delayed antibody responses and
      failed to clear virus from the periphery. Severe neurological signs and
      obtundation characterized end stage-disease in IN-inoculated mice, and within the
      CNS, the development of peak virus RNA loads coincided with strong
      proinflammatory responses and infiltration of activated T cells. Interestingly,
      depletion of T cells did not significantly alter survival, suggesting that
      neurologic disease is not a by-product of an aberrant immune response.
      CONCLUSIONS/SIGNIFICANCE: Comparison of fatal (IN-inoculated) and nonfatal (FP
      inoculated) DeltaNSs RVFV infections in the mouse model highlighted the role of
      the host immune response in controlling viral replication and therefore
      determining clinical outcome. There was no evidence to suggest that neurologic
      disease is immune-mediated in RVFV infection. These results provide important
      insights for the future design of vaccines and therapeutic options.

PMID- 24922482
TI  - Capture and Amplification by Tailing and Switching (CATS). An ultrasensitive
      ligation-independent method for generation of DNA libraries for deep sequencing
      from picogram amounts of DNA and RNA.
AB  - Massive parallel sequencing (MPS) technologies have paved the way into new areas
      of research including individualized medicine. However, sequencing of trace
      amounts of DNA or RNA still remains a major challenge, especially for degraded
      nucleic acids like circulating DNA. This together with high cost and time
      requirements impedes many important applications of MPS in medicine and
      fundamental science. We have established a fast, cheap and highly efficient
      protocol called 'Capture and Amplification by Tailing and Switching' (CATS) to
      directly generate ready-to-sequence libraries for MPS from nanogram and picogram
      quantities of both DNA and RNA. Furthermore, those DNA libraries are strand
      specific, can be prepared within 2-3 h and do not require preliminary sample
      amplification steps. To exemplify the capacity of the technique, we have
      generated and sequenced DNA libraries from hundred-picogram amounts of
      circulating nucleic acids isolated from human blood plasma, one nanogram of mRNA
      enriched total RNA from cultured cells and few nanograms of bisulfite-converted
      DNA. The approach for DNA library preparation from minimal and fragmented input
      described here will find broad application in diverse research areas such as
      translational medicine including therapy monitoring, prediction, prognosis and
      early detection of various human disorders and will permit high-throughput DNA
      sequencing from previously inaccessible material such as minute forensic and
      archeological samples. 

PMID- 24922483
TI  - Model selection in systems biology depends on experimental design.
AB  - Experimental design attempts to maximise the information available for modelling
      tasks. An optimal experiment allows the inferred models or parameters to be
      chosen with the highest expected degree of confidence. If the true system is
      faithfully reproduced by one of the models, the merit of this approach is clear -
      we simply wish to identify it and the true parameters with the most certainty.
      However, in the more realistic situation where all models are incorrect or
      incomplete, the interpretation of model selection outcomes and the role of
      experimental design needs to be examined more carefully. Using a novel
      experimental design and model selection framework for stochastic state-space
      models, we perform high-throughput in-silico analyses on families of gene
      regulatory cascade models, to show that the selected model can depend on the
      experiment performed. We observe that experimental design thus makes confidence a
      criterion for model choice, but that this does not necessarily correlate with a
      model's predictive power or correctness. Finally, in the special case of linear
      ordinary differential equation (ODE) models, we explore how wrong a model has to
      be before it influences the conclusions of a model selection analysis. 

PMID- 24922484
TI  - Cognitive processing therapy for posttraumatic stress disorder delivered to rural
      veterans via telemental health: a randomized noninferiority clinical trial.
AB  - OBJECTIVE: To compare clinical and process outcomes of cognitive processing
      therapy-cognitive only version (CPT-C) delivered via videoteleconferencing (VTC)
      to in-person in a rural, ethnically diverse sample of veterans with posttraumatic
      stress disorder (PTSD). METHOD: A randomized clinical trial with a noninferiority
      design was used to determine if providing CPT-C via VTC is effective and "as good
      as" in-person delivery. The study took place between March 2009 and June 2013.
      PTSD was diagnosed per DSM-IV. Participants received 12 sessions of CPT-C via VTC
      (n = 61) or in-person (n = 64). Assessments were administered at baseline,
      midtreatment, immediately posttreatment, and 3 and 6 months posttreatment. The
      primary clinical outcome was posttreatment PTSD severity, as measured by the
      Clinician-Administered PTSD Scale. RESULTS: Clinical and process outcomes found
      VTC to be noninferior to in-person treatment. Significant reductions in PTSD
      symptoms were identified at posttreatment (Cohen d = 0.78, P < .05) and
      maintained at 3- and 6-month follow-up (d = 0.73, P < .05 and d = 0.76, P < .05,
      respectively). High levels of therapeutic alliance, treatment compliance, and
      satisfaction and moderate levels of treatment expectancies were reported, with no
      differences between groups (for all comparisons, F < 1.9, P > .17). CONCLUSIONS:
      Providing CPT-C to rural residents with PTSD via VTC produced outcomes that were
      "as good as" in-person treatment. All participants demonstrated significant
      reductions in PTSD symptoms posttreatment and at follow-up. Results indicate that
      VTC can offer increased access to specialty mental health care for residents of
      rural or remote areas. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00879255.

PMID- 24922485
TI  - Repetitive transcranial magnetic stimulation for treatment-resistant depression:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy of repetitive transcranial magnetic
      stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more
      prior antidepressant treatment failures (often referred to as treatment-resistant
      depression [TRD]). These patients are less likely to recover with medications
      alone and often consider nonpharmacologic treatments such as rTMS. DATA SOURCES:
      We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the
      International Pharmaceutical Abstracts for studies comparing rTMS with a sham
      controlled treatment in TRD patients ages 18 years or older. STUDY SELECTION: We
      included 18 good- or fair-quality TRD studies published from January 1, 1980,
      through March 20, 2013. DATA EXTRACTION: We abstracted relevant data, assessed
      each study's internal validity, and graded strength of evidence for change in
      depressive severity, response rates, and remission rates. RESULTS: rTMS was
      beneficial compared with sham for all outcomes. rTMS produced a greater decrease
      in depressive severity (high strength of evidence), averaging a clinically
      meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4
      points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS
      resulted in greater response rates (high strength of evidence); those receiving
      rTMS were more than 3 times as likely to respond as patients receiving sham
      (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to
      produce remission (moderate strength of evidence); patients receiving rTMS were
      more than 5 times as likely to achieve remission as those receiving sham
      (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable
      treatment parameters prevented conclusions about which specific treatment options
      are more effective than others. How long these benefits persist remains unclear.
      CONCLUSIONS: For MDD patients with 2 or more antidepressant treatment failures,
      rTMS is a reasonable, effective consideration.

PMID- 24922486
TI  - Age in school cohort, borderline personality disorder, and neurofeedback.

PMID- 24922487
TI  - The youngest children in each school cohort are overrepresented in referrals to
      mental health services.
AB  - OBJECTIVE: To investigate whether the youngest children in each school cohort are
      overrepresented as users of specialist mental health services. METHOD: Dates of
      birth were obtained for all 9,157 children and adolescents referred to specialist
      mental health services in 3 London boroughs from 2008 to 2011. The actual
      frequency of referrals by month of birth is compared to the expected frequency of
      referrals as determined by birth statistics for the relevant age group. RESULTS:
      August-born children, who are the youngest in their cohorts in England, represent
      9.38% of referrals but only 8.59% of the population in the relevant age segment.
      Hence, August-born children are overrepresented in referrals to specialist mental
      health services (P value = .007). September- and October-born children, who are
      the oldest in their cohorts, are underrepresented: September-born children
      represent 8.62% of the population but 7.99% of referrals to mental health
      services (P value = .032), and October-born children are 8.56% of the population
      but 7.86% of referrals (P value = .016). CONCLUSIONS: Being among the youngest in
      a school cohort is associated with a higher risk of referral to mental health
      services, while being among the oldest is a protective factor.

PMID- 24922488
TI  - Neurocognitive effects of neurofeedback in adolescents with ADHD: a randomized
      controlled trial.
AB  - OBJECTIVE: Neurofeedback aims to reduce symptoms of attention
      deficit/hyperactivity disorder (ADHD), mainly attention problems. However, the
      additional influence of neurofeedback over treatment as usual (TAU) on
      neurocognitive functioning for adolescents with ADHD remains unclear. METHOD: By
      using a multicenter parallel randomized controlled trial (RCT) design, male
      adolescents with a DSM-IV-TR diagnosis of ADHD (mean age = 16.1 years; range, 12
      24) were randomized to receive either a combination of TAU and neurofeedback (n =
      45) or TAU (n = 26). Randomization was computer generated and stratified by age
      group (ages 12 through 15, 16 through 20, and 21 through 24 years). The
      neurofeedback intervention consisted of approximately 37 sessions over a period
      of 25 weeks of theta/sensorimotor rhythm training on the vertex (Cz). Primary
      neurocognitive outcomes included performance parameters derived from the D2 Test
      of Attention, the Digit Span backward, the Stroop Color-Word Test and the Tower
      of London, all assessed preintervention and postintervention. Data were collected
      between December 2009 and July 2012. RESULTS: At postintervention, outcomes of
      attention and/or motor speed were improved, with faster processing times for both
      intervention conditions and with medium to large effect sizes (range, etap2 = .08
      .54; P values < .023). In both groups, no improvements for higher executive
      functions were observed. Results might partly resemble practice effects.
      CONCLUSIONS: Although neurocognitive outcomes improved in all adolescents
      receiving treatment for ADHD, no additional value for neurofeedback over TAU was
      observed. Hence, this study does not provide evidence for using
      theta/sensorimotor rhythm neurofeedback to enhance neurocognitive performance as
      additional intervention to TAU for adolescents with ADHD symptoms. TRIAL
      REGISTRATION: Trialregister.nl identifier: 1759.

PMID- 24922489
TI  - Translating clinical science into effective therapies.
AB  - Identifying a patient with treatment-resistant depression involves ensuring that
      at least 2 evidence-based antidepressant trials from two different pharmacologic
      classes have been undertaken and determining their impact on patients' symptoms,
      functioning, quality-of-life and social relationships as outcomes. When assessing
      depressive symptoms throughout the course of treatment, clinical judgment should
      be supplemented by using standardized tools such as the 9-item Patient Health
      Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology
      (QIDS). Adjunctive treatment strategies preserve the benefits of first-line
      antidepressants in partial responders and potentially enhance the initial
      antidepressant's effect through complementary mechanisms of action. Novel
      "multimodal" pharmacotherapies with diverse potentially beneficial mechanisms of
      action are in development, which have varying degrees of activity across multiple
      monoamine systems including those regulated by serotonin, dopamine, and
      glutamate. 

PMID- 24922490
TI  - Monitoring pharmacotherapy response, safety, and tolerability to enhance
      adherence in bipolar disorder.
AB  - Among patients with bipolar disorder, treatment nonadherence can be triggered by
      lack of response or by medication-induced adverse effects. To track treatment
      response, clinicians can have patients complete daily life and mood charts to
      provide accurate information over time on patients' mood, adherence, side
      effects, and life events. Rating scales like the CGI-BP are also an option for
      assessing treatment response. In addition, clinicians should monitor patients for
      common side effects related to bipolar depression treatments, such as sedation
      and weight gain/metabolic abnormalities, which lead to increased medical problems
      and shortened life expectancy. By implementing specific interventions to address
      these effects, clinicians can help promote optimal outcomes for patients with
      bipolar disorder. 

PMID- 24922491
TI  - Obsessive-compulsive disorder in youth: assessment and treatment.
AB  - For pediatric patients with obsessive-compulsive disorder, clinicians must
      address particular diagnostic and treatment challenges. Children with obsessive
      compulsive disorder may have little insight into their obsessions and
      compulsions, requiring clinicians to provide age-appropriate education,
      motivation, and therapy. Treatment should take into account children's
      developmental level, family accommodation, and comorbidities. If the onset of
      obsessive-compulsive disorder is sudden, clinicians may use pediatric acute-onset
      neuropsychiatric syndrome criteria and conduct appropriate tests. 

PMID- 24922492
TI  - A primer for the conceptualization of the mechanism of action of
      electroconvulsive therapy, 1: defining the question.
AB  - With regard to the question of how electroconvulsive therapy (ECT) acts, a common
      answer is that the mechanism of action of the treatment is not well understood.
      However, this is not true. There is a great deal of information available about
      what ECT does in the brain, how it does it, and how these effects translate into
      clinical actions. The very complexity of the available data makes it necessary
      for the question about mechanisms to be properly defined with regard to
      physiologic effects, adverse effects, and efficacy in different conditions. This
      article presents a primer for the conceptualization of the mechanism of action of
      ECT with special attention to understanding why the question and answer are
      complex. 

PMID- 24922493
TI  - Update on best practices for managing bipolar depression.

PMID- 24922494
TI  - Clinical predictors of ketamine response in treatment-resistant major depression.
AB  - OBJECTIVE: The N-methyl-D-aspartate receptor antagonist ketamine has rapid
      antidepressant effects in treatment-resistant major depressive disorder (MDD) and
      bipolar depression. Clinical predictors may identify those more likely to benefit
      from ketamine within clinically heterogeneous populations. METHOD: Data were
      analyzed from 4 studies of treatment-resistant inpatients with DSM-IV-TR
      diagnosed MDD or bipolar I or II depression. Patients who were currently
      experiencing a moderate-to-severe major depressive episode were enrolled between
      November 2004 and March 2013. All subjects received a single subanesthetic (0.5
      mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230
      minute postinfusion time point (n = 108), at day 1 (n = 82), and at day 7 (n =
      71). Univariate Pearson correlations were performed for each variable with
      percent change from baseline in the 17-item Hamilton Depression Rating Scale
      (HDRS). Multivariate linear regression was then conducted for statistically
      significant predictors (P <= .05, 2-tailed). RESULTS: Higher body mass index
      correlated with greater HDRS improvement at 230 minutes (standardized beta = 
      0.30, P = .004) and at day 1 (standardized beta = -0.37, P = .001), but not at
      day 7 (standardized beta = -0.18, P = .10). Family history of an alcohol use
      disorder in a first-degree relative was associated with greater HDRS improvement
      at day 1 (standardized beta = -0.27, P = .014) and day 7 (standardized beta = 
      0.41, P < .001). No prior history of suicide attempt(s) was associated with
      greater improvement only at day 7 (standardized beta = 0.28, P = .01). The
      overall statistical model explained 13%, 23%, and 36% of HDRS percent change
      variance at 230 minutes, day 1, and day 7, respectively. CONCLUSIONS: Despite its
      post hoc nature, this study identified several clinical correlates of ketamine's
      rapid and durable antidepressant effects. Further investigation of these
      relationships is critical for individualized treatment of depression.

PMID- 24922495
TI  - Pharmacologic and behavioral interventions to improve cardiovascular risk factors
      in adults with serious mental illness: a systematic review and meta-analysis.
AB  - OBJECTIVE: Individuals with serious mental illness have high rates of
      cardiovascular disease (CVD) risk factors and mortality. This systematic review
      was conducted to evaluate pharmacologic and behavioral interventions to reduce
      CVD risk in adults with serious mental illness. DATA SOURCES: MEDLINE, EMBASE,
      PsycINFO, ClinicalTrials.gov, and Cochrane Database of Systematic Reviews were
      searched from January 1980 to July 2012 for English language studies. Examples of
      search terms used include schizophrenia, bipolar disorder, antipsychotics,
      weight, glucose, lipid, and cardiovascular disease. STUDY SELECTION: Two
      reviewers independently screened citations and identified 33 randomized
      controlled trials of at least 2 months' duration that enrolled adults with
      serious mental illness and evaluated pharmacologic or behavioral interventions
      targeting weight, glucose, or lipid control. DATA EXTRACTION: Reviewers extracted
      data, assessed applicability, and evaluated study quality; the team jointly
      graded overall strength of evidence. RESULTS: We included 33 studies. Most
      studies targeted weight control (28 studies). Compared with control groups,
      weight control was improved with behavioral interventions (mean difference = 
      3.13 kg; 95% CI, -4.21 to -2.05), metformin (mean difference = -4.13 kg; 95% CI, 
      6.58 to -1.68), anticonvulsive medications topiramate and zonisamide (mean
      difference = -5.11 kg; 95% CI, -9.48 to -0.74), and adjunctive or antipsychotic
      switching to aripiprazole (meta-analysis not possible). Evidence was insufficient
      for all other interventions and for effects on glucose and lipid control. The
      small number of studies precluded analyses of variability in treatment effects by
      patient characteristics. CONCLUSIONS: Few studies have evaluated interventions
      addressing 1 or more CVD risk factors in people with serious mental illness.
      Glucose- and lipid-related results were mainly reported as secondary outcome
      assessments in studies of weight-management interventions. Comparative
      effectiveness studies are needed to test multimodal strategies, agents known to
      be effective in nonserious mental illness populations, and antipsychotic
      management strategies.

PMID- 24922496
TI  - Meta-analysis of selective serotonin reuptake inhibitor-associated QTc
      prolongation.
AB  - OBJECTIVE: To evaluate the association between selective serotonin reuptake
      inhibitors (SSRIs) and corrected QT interval (QTc) prolongation via meta-analysis
      of prospective studies. DATA SOURCES: PubMed/MEDLINE database (January 1, 1975
      August 15, 2012), with additional reports identified using hand searches of
      reference lists of relevant articles. Key words searched were QT, torsades de
      pointes, and sudden cardiac death, combined with antidepressants, citalopram,
      escitalopram, fluoxetine, sertraline, paroxetine, and fluvoxamine. English-,
      Spanish-, and German-language articles were included. STUDY SELECTION: Two
      reviewers independently identified prospective controlled studies in adults that
      reported data related to QTc intervals prior to and following treatment with
      SSRIs. DATA EXTRACTION AND SYNTHESIS: Three reviewers independently extracted
      study-level data including population characteristics, method of QTc measurement
      and treatment and outcome data. Two independent reviewers critiqued study
      quality. Publication bias was assessed visually using a funnel plot and
      quantitatively. Heterogeneity was measured using Cochran Q statistic. RESULTS:
      Sixteen articles (with 25 distinct data subsets) involving 4,292 patients were
      included. SSRIs were associated with a dose-dependent increase in QTc interval
      compared to placebo (+6.10 milliseconds; 95% CI, 3.47-8.73; P < .001). Tricyclic
      antidepressants (TCAs) were associated with a significantly greater QTc increase
      than SSRIs (TCA prolongation, 7.05 milliseconds; 95% CI, 3.84-10.27 greater than
      SSRIs; P < .001). With respect to specific SSRI agents, citalopram was associated
      with significantly greater QTc prolongation than sertraline, paroxetine, and
      fluvoxamine. CONCLUSIONS: SSRIs were associated with a modest but statistically
      significant increase in the QTc interval, although to a lesser extent than TCAs;
      this finding was not limited to any single study. Citalopram was associated with
      more QTc prolongation than most other SSRIs.

PMID- 24922497
TI  - Clinical staging in bipolar disorder: focus on cognition and functioning.
AB  - OBJECTIVE: Clinical staging has increasingly been considered suitable for
      psychiatric disorders such as bipolar disorder. A staging model of bipolar
      disorder could help clinicians understand the mechanisms underlying the course of
      the illness and guide prognosis and therapy. This study aimed to investigate
      differences in functional status and cognitive functioning in patients in
      different clinical stages of bipolar disorder. METHOD: Subjects who met DSM-IV
      criteria for bipolar disorder (n = 54) were recruited from the Bipolar Disorders
      Program at Hospital de Clinicas de Porto Alegre (Brazil) from October 2012 to
      October 2013. All patients had been in remission (score < 7 on the 17-item HDRS
      and the YMRS) for at least 1 month before assessment. They were classified into 4
      clinical stages according to the model described by Kapczinski et al and compared
      to 43 healthy controls. Functional status was assessed by using the Functioning
      Assessment Short Test (FAST). Neuropsychological measures were performed to
      investigate cognitive functioning. RESULTS: Significant differences in functional
      status were found between patients in all stages compared to controls (F =
      33.014, P < .001), except for stage I (P = .104). Additionally, a very strong
      linear association was found between FAST scores and clinical stages, with FAST
      scores increasing from stage I to IV (F = 149.55, P < .001). In the bipolar
      group, stage I was associated with better occupational functioning than stage II
      (F = 48.344, P = .003). Stage IV patients experienced greater impairment in
      autonomy than stage III patients (F = 26.646, P = .004), and stage III patients
      experienced poorer autonomy than those in stage II (P = .004). With regard to
      cognitive measures, patients in late stages (stages III and IV) were more
      impaired than healthy controls (P < .001). A similar performance was found
      between patients in early stages (stages I and II) and healthy controls.
      DISCUSSION: This study showed progressive functional changes from stage I to
      stage IV of bipolar disorder, with a greater impairment in patients in later
      stages of the illness. FAST scores seem to have a good discriminant ability to
      distinguish between patients in early versus late stages of bipolar disorder and
      could therefore contribute to the development of a bipolar disorder staging
      system.

PMID- 24922498
TI  - Psychiatric comorbidity in hospitalized adolescents with borderline personality
      disorder.
AB  - OBJECTIVE: The goal of this study was to carry out the first comprehensive
      assessment of psychiatric comorbidity in adolescents (aged 12-17 years) with DSM
      IV criteria for borderline personality disorder (BPD) compared to a psychiatric
      comparison group without BPD. Complex comorbidity (a hallmark feature of adult
      BPD and defined as having any mood or anxiety disorder plus a disorder of
      impulsivity) was also examined as a distinguishing feature of adolescent BPD.
      METHOD: Consecutively admitted patients (October 2008 to October 2012) to an
      inpatient psychiatric hospital received parental consent and gave assent for
      participation in the study (N = 418), with the final sample after exclusions
      consisting of 335 adolescent inpatients. A comprehensive, multimethod approach to
      determining psychiatric comorbidity was used, including both an interview-based
      (categorical) and a questionnaire-based (dimensional) assessment as well as both
      parent and adolescent self-report. Measures included the Diagnostic Interview
      Schedule for Children (NIMH-DISC-IV), Child Behavior Checklist (CBCL), Youth Self
      Report (YSR), Car, Relax Alone, Forget, Friends, Trouble (CRAFFT), and the
      Childhood Interview for DSM-IV Borderline Personality Disorder (CI-BPD). RESULTS:
      Thirty-three percent of the final sample met criteria for BPD. Adolescent
      inpatients with BPD showed significantly higher rates of psychiatric comorbidity
      compared to non-BPD psychiatric subjects for both internalizing (chi21 = 27.40, P
      < .001) and externalizing (chi21 = 19.02, P < .001) diagnosis. Similarly, using
      dimensional scores for self-reported symptoms, adolescent inpatients with BPD had
      significantly higher rates of psychiatric comorbidity compared to non-BPD
      subjects for internalizing (t329 = -6.63, P < .001) and externalizing (t329 = 
      7.14, P < .001) problems. Parent-reported symptoms were significantly higher in
      the BPD group only when using a dimensional approach (internalizing: t321 = 
      3.42, P < .001; externalizing: t321 = -3.32, P < .001). Furthermore,
      significantly higher rates of complex comorbidity were found for adolescents with
      BPD (chi21 = 26.60, P < .001). Moreover, externalizing and internalizing problems
      interacted in association with borderline traits (B = .25; P < .001).
      CONCLUSIONS: Similar to findings in adult studies of BPD, adolescents with BPD
      demonstrate significantly more complex comorbidity compared to psychiatric
      subjects without BPD.

PMID- 24922499
TI  - Enantioselective rhodium-catalyzed arylation of cyclic N-sulfamidate
      alkylketimines: a new access to chiral beta-alkyl-beta-aryl amino alcohols.
AB  - The enantioselective rhodium-catalyzed 1,2-addition of arylboronates to cyclic N
      sulfamidate alkylketimines was developed. With a rhodium/diene complex as
      catalyst, high enantioselectivity and broad functional group tolerance were
      observed. The resulting sulfamidates can easily be converted into chiral beta
      alkyl-beta-aryl amino alcohols. 

PMID- 24922500
TI  - A semiparametric Bayesian model for detecting synchrony among multiple neurons.
AB  - We propose a scalable semiparametric Bayesian model to capture dependencies among
      multiple neurons by detecting their cofiring (possibly with some lag time)
      patterns over time. After discretizing time so there is at most one spike at each
      interval, the resulting sequence of 1s (spike) and 0s (silence) for each neuron
      is modeled using the logistic function of a continuous latent variable with a
      gaussian process prior. For multiple neurons, the corresponding marginal
      distributions are coupled to their joint probability distribution using a
      parametric copula model. The advantages of our approach are as follows. The
      nonparametric component (i.e., the gaussian process model) provides a flexible
      framework for modeling the underlying firing rates, and the parametric component
      (i.e., the copula model) allows us to make inferences regarding both
      contemporaneous and lagged relationships among neurons. Using the copula model,
      we construct multivariate probabilistic models by separating the modeling of
      univariate marginal distributions from the modeling of a dependence structure
      among variables. Our method is easy to implement using a computationally
      efficient sampling algorithm that can be easily extended to high-dimensional
      problems. Using simulated data, we show that our approach could correctly capture
      temporal dependencies in firing rates and identify synchronous neurons. We also
      apply our model to spike train data obtained from prefrontal cortical areas. 

PMID- 24922501
TI  - Continuous closed-loop decoder adaptation with a recursive maximum likelihood
      algorithm allows for rapid performance acquisition in brain-machine interfaces.
AB  - Closed-loop decoder adaptation (CLDA) is an emerging paradigm for both improving
      and maintaining online performance in brain-machine interfaces (BMIs). The time
      required for initial decoder training and any subsequent decoder recalibrations
      could be potentially reduced by performing continuous adaptation, in which
      decoder parameters are updated at every time step during these procedures, rather
      than waiting to update the decoder at periodic intervals in a more batch-based
      process. Here, we present recursive maximum likelihood (RML), a CLDA algorithm
      that performs continuous adaptation of a Kalman filter decoder's parameters. We
      demonstrate that RML possesses a variety of useful properties and practical
      algorithmic advantages. First, we show how RML leverages the accuracy of updates
      based on a batch of data while still adapting parameters on every time step.
      Second, we illustrate how the RML algorithm is parameterized by a single,
      intuitive half-life parameter that can be used to adjust the rate of adaptation
      in real time. Third, we show how even when the number of neural features is very
      large, RML's memory-efficient recursive update rules can be reformulated to also
      be computationally fast so that continuous adaptation is still feasible. To test
      the algorithm in closed-loop experiments, we trained three macaque monkeys to
      perform a center-out reaching task by using either spiking activity or local
      field potentials to control a 2D computer cursor. RML achieved higher levels of
      performance more rapidly in comparison to a previous CLDA algorithm that adapts
      parameters on a more intermediate timescale. Overall, our results indicate that
      RML is an effective CLDA algorithm for achieving rapid performance acquisition
      using continuous adaptation. 

PMID- 24922502
TI  - Sparseness, antisparseness and anything in between: the operating point of a
      neuron determines its computational repertoire.
AB  - A recent model of intrinsic plasticity coupled to Hebbian synaptic plasticity
      proposes that adaptation of a neuron's threshold and gain in a sigmoidal response
      function to achieve a sparse, exponential output firing rate distribution
      facilitates the discovery of heavy-tailed or super- gaussian sources in the
      neuron's inputs. We show that the exponential output distribution is irrelevant
      to these dynamics and that, furthermore, while sparseness is sufficient, it is
      not necessary. The intrinsic plasticity mechanism drives the neuron's threshold
      large and positive, and we prove that in such a regime, the neuron will find
      supergaussian sources; equally, however, if the threshold is large and negative
      (an antisparse regime), it will also find supergaussian sources. Away from such
      extremes, the neuron can also discover subgaussian sources. By examining a neuron
      with a fixed sigmoidal nonlinearity and considering the synaptic strength fixed
      point structure in the two-dimensional parameter space defined by the neuron's
      threshold and gain, we show that this space is carved up into sub- and
      supergaussian-input-finding regimes, possibly with regimes of simultaneous
      stability of sub- and supergaussian sources or regimes of instability of all
      sources; a single gaussian source may also be stabilized by the presence of a
      nongaussian source. A neuron's operating point (essentially its threshold and
      gain coupled with its input statistics) therefore critically determines its
      computational repertoire. Intrinsic plasticity mechanisms induce trajectories in
      this parameter space but do not fundamentally modify it. Unless the trajectories
      cross critical boundaries in this space, intrinsic plasticity is irrelevant and
      the neuron's nonlinearity may be frozen with identical receptive field refinement
      dynamics. 

PMID- 24922503
TI  - Synchronization of stochastic competitive neural networks with different
      timescales and reaction-diffusion terms.
AB  - We propose a feedback controller for the synchronization of stochastic
      competitive neural networks with different timescales and reaction-diffusion
      terms. By constructing a proper Lyapunov-Krasovskii functional, as well as
      employing stochastic analysis theory, the LaShall-type invariance principle for
      stochastic differential delay equations, and a linear matrix inequality (LMI)
      technique, a feedback controller is designed to achieve the asymptotical
      synchronization of coupled stochastic competitive neural networks. A simulation
      example is given to show the effectiveness of the theoretical results. 

PMID- 24922504
TI  - A nonparametric clustering algorithm with a quantile-based likelihood estimator.
AB  - Clustering is a representative of unsupervised learning and one of the important
      approaches in exploratory data analysis. By its very nature, clustering without
      strong assumption on data distribution is desirable. Information-theoretic
      clustering is a class of clustering methods that optimize information-theoretic
      quantities such as entropy and mutual information. These quantities can be
      estimated in a nonparametric manner, and information-theoretic clustering
      algorithms are capable of capturing various intrinsic data structures. It is also
      possible to estimate information-theoretic quantities using a data set with
      sampling weight for each datum. Assuming the data set is sampled from a certain
      cluster and assigning different sampling weights depending on the clusters, the
      cluster-conditional information-theoretic quantities are estimated. In this
      letter, a simple iterative clustering algorithm is proposed based on a
      nonparametric estimator of the log likelihood for weighted data sets. The
      clustering algorithm is also derived from the principle of conditional entropy
      minimization with maximum entropy regularization. The proposed algorithm does not
      contain a tuning parameter. The algorithm is experimentally shown to be
      comparable to or outperform conventional nonparametric clustering methods. 

PMID- 24922505
TI  - Neuronal spike train entropy estimation by history clustering.
AB  - Neurons send signals to each other by means of sequences of action potentials
      (spikes). Ignoring variations in spike amplitude and shape that are probably not
      meaningful to a receiving cell, the information content, or entropy of the signal
      depends on only the timing of action potentials, and because there is no external
      clock, only the interspike intervals, and not the absolute spike times, are
      significant. Estimating spike train entropy is a difficult task, particularly
      with small data sets, and many methods of entropy estimation have been proposed.
      Here we present two related model-based methods for estimating the entropy of
      neural signals and compare them to existing methods. One of the methods is fast
      and reasonably accurate, and it converges well with short spike time records; the
      other is impractically time-consuming but apparently very accurate, relying on
      generating artificial data that are a statistical match to the experimental data.
      Using the slow, accurate method to generate a best-estimate entropy value, we
      find that the faster estimator converges to this value more closely and with
      smaller data sets than many existing entropy estimators. 

PMID- 24922506
TI  - Influence of external inputs and asymmetry of connections on information
      geometric measures involving up to ten neuronal interactions.
AB  - The investigation of neural interactions is crucial for understanding information
      processing in the brain. Recently an analysis method based on information
      geometry (IG) has gained increased attention, and the property of the pairwise IG
      measure has been studied extensively in relation to the two-neuron interaction.
      However, little is known about the property of IG measures involving more
      neuronal interactions. In this study, we systematically investigated the
      influence of external inputs and the asymmetry of connections on the IG measures
      in cases ranging from 1-neuron to 10-neuron interactions. First, the analytical
      relationship between the IG measures and external inputs was derived for a
      network of 10 neurons with uniform connections. Our results confirmed that the
      single and pairwise IG measures were good estimators of the mean background input
      and of the sum of the connection weights, respectively. For the IG measures
      involving 3 to 10 neuronal interactions, we found that the influence of external
      inputs was highly nonlinear. Second, by computer simulation, we extended our
      analytical results to asymmetric connections. For a network of 10 neurons, the
      simulation showed that the behavior of the IG measures in relation to external
      inputs was similar to the analytical solution obtained for a uniformly connected
      network. When the network size was increased to 1000 neurons, the influence of
      external inputs almost disappeared. This result suggests that all IG measures
      from 1-neuron to 10-neuron interactions are robust against the influence of
      external inputs. In addition, we investigated how the strength of asymmetry
      influenced the IG measures. Computer simulation of a 1000-neuron network showed
      that all the IG measures were robust against the modulation of the asymmetry of
      connections. Our results provide further support for an information-geometric
      approach and will provide useful insights when these IG measures are applied to
      real experimental spike data. 

PMID- 24922507
TI  - The transcription factor TFII-I promotes DNA translesion synthesis and genomic
      stability.
AB  - Translesion synthesis (TLS) enables DNA replication through damaged bases,
      increases cellular DNA damage tolerance, and maintains genomic stability. The
      sliding clamp PCNA and the adaptor polymerase Rev1 coordinate polymerase
      switching during TLS. The polymerases Pol eta, iota, and kappa insert nucleotides
      opposite damaged bases. Pol zeta, consisting of the catalytic subunit Rev3 and
      the regulatory subunit Rev7, then extends DNA synthesis past the lesion. Here, we
      show that Rev7 binds to the transcription factor TFII-I in human cells. TFII-I is
      required for TLS and DNA damage tolerance. The TLS function of TFII-I appears to
      be independent of its role in transcription, but requires homodimerization and
      binding to PCNA. We propose that TFII-I bridges PCNA and Pol zeta to promote TLS.
      Our findings extend the general principle of component sharing among divergent
      nuclear processes and implicate TLS deficiency as a possible contributing factor
      in Williams-Beuren syndrome. 

PMID- 24922509
TI  - Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN).
AB  - This study aimed at investigating the fecal microbiota, and the fecal and urinary
      metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin
      A nephropathy (IgAN). Three groups of volunteers were included in the study: (i)
      sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy
      control (HC) subjects, without known diseases. Selective media were used to
      determine the main cultivable bacterial groups. Bacterial tag-encoded FLX
      titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to
      determine total and metabolically active bacteria, respectively. Biochrom 30
      series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase
      microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic
      analyses. As estimated by rarefaction, Chao and Shannon diversity index, the
      lowest microbial diversity was found in P patients. Firmicutes increased in the
      fecal samples of NP and, especially, P patients due to the higher percentages of
      some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and
      Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and
      Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae,
      Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP,
      P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the
      highest in the fecal samples of NP and/or P patients. Compared to HC subjects,
      Bifidobacterium species decreased in the fecal samples of NP and P. As shown by
      multivariate statistical analyses, the levels of metabolites (free amino acids
      and organic volatile compounds) from fecal and urinary samples markedly
      differentiated NP and, especially, P patients. 

PMID- 24922510
TI  - Proteomic selection of immunodiagnostic antigens for Trypanosoma congolense.
AB  - Animal African Trypanosomosis (AAT) presents a severe problem for agricultural
      development in sub-Saharan Africa. It is caused by several trypanosome species
      and current means of diagnosis are expensive and impractical for field use. Our
      aim was to discover antigens for the detection of antibodies to Trypanosoma
      congolense, one of the main causative agents of AAT. We took a proteomic approach
      to identify potential immunodiagnostic parasite protein antigens. One hundred and
      thirteen proteins were identified which were selectively recognized by infected
      cattle sera. These were assessed for likelihood of recombinant protein expression
      in E. coli and fifteen were successfully expressed and assessed for their
      immunodiagnostic potential by ELISA using pooled pre- and post-infection cattle
      sera. Three proteins, members of the invariant surface glycoprotein (ISG) family,
      performed favorably and were then assessed using individual cattle sera. One
      antigen, Tc38630, evaluated blind with 77 randomized cattle sera in an ELISA
      assay gave sensitivity and specificity performances of 87.2% and 97.4%,
      respectively. Cattle immunoreactivity to this antigen diminished significantly
      following drug-cure, a feature helpful for monitoring the efficacy of drug
      treatment. 

PMID- 24922508
TI  - Computational modeling of allosteric regulation in the hsp90 chaperones: a
      statistical ensemble analysis of protein structure networks and allosteric
      communications.
AB  - A fundamental role of the Hsp90 chaperone in regulating functional activity of
      diverse protein clients is essential for the integrity of signaling networks. In
      this work we have combined biophysical simulations of the Hsp90 crystal
      structures with the protein structure network analysis to characterize the
      statistical ensemble of allosteric interaction networks and communication
      pathways in the Hsp90 chaperones. We have found that principal structurally
      stable communities could be preserved during dynamic changes in the
      conformational ensemble. The dominant contribution of the inter-domain rigidity
      to the interaction networks has emerged as a common factor responsible for the
      thermodynamic stability of the active chaperone form during the ATPase cycle.
      Structural stability analysis using force constant profiling of the inter-residue
      fluctuation distances has identified a network of conserved structurally rigid
      residues that could serve as global mediating sites of allosteric communication.
      Mapping of the conformational landscape with the network centrality parameters
      has demonstrated that stable communities and mediating residues may act
      concertedly with the shifts in the conformational equilibrium and could describe
      the majority of functionally significant chaperone residues. The network analysis
      has revealed a relationship between structural stability, global centrality and
      functional significance of hotspot residues involved in chaperone regulation. We
      have found that allosteric interactions in the Hsp90 chaperone may be mediated by
      modules of structurally stable residues that display high betweenness in the
      global interaction network. The results of this study have suggested that
      allosteric interactions in the Hsp90 chaperone may operate via a mechanism that
      combines rapid and efficient communication by a single optimal pathway of
      structurally rigid residues and more robust signal transmission using an ensemble
      of suboptimal multiple communication routes. This may be a universal requirement
      encoded in protein structures to balance the inherent tension between resilience
      and efficiency of the residue interaction networks. 

PMID- 24922511
TI  - A replication study for genome-wide gene expression levels in two layer lines
      elucidates differentially expressed genes of pathways involved in bone remodeling
      and immune responsiveness.
AB  - The current replication study confirmed significant differences in gene
      expression profiles of the cerebrum among the two commercial layer lines Lohmann
      Selected Leghorn (LSL) and Lohmann Brown (LB). Microarray analyses were performed
      for 30 LSL and another 30 LB laying hens kept in the small group housing system
      Eurovent German. A total of 14,103 microarray probe sets using customized
      Affymetrix ChiGene-1_0-st Arrays with 20,399 probe sets were differentially
      expressed among the two layer lines LSL and LB (FDR adjusted P-value <0.05). An
      at least 2-fold change in expression levels could be observed for 388 of these
      probe sets. In LSL, 214 of the 388 probe sets were down- and 174 were up
      regulated and vice versa for the LB layer line. Among the 174 up-regulated probe
      sets in LSL, we identified 51 significantly enriched Gene ontology (GO) terms of
      the biological process category. A total of 63 enriched GO-terms could be
      identified for the 214 down-regulated probe sets of the layer line LSL. We
      identified nine genes significantly differentially expressed between the two
      layer lines in both microarray experiments. These genes play a crucial role in
      protection of neuronal cells from oxidative stress, bone mineral density and
      immune response among the two layer lines LSL and LB. Thus, the different
      regulation of these genes may significantly contribute to phenotypic trait
      differences among these layer lines. In conclusion, these novel findings provide
      a basis for further research to improve animal welfare in laying hens and these
      layer lines may be of general interest as an animal model. 

PMID- 24922512
TI  - Dissociative part-dependent resting-state activity in dissociative identity
      disorder: a controlled FMRI perfusion study.
AB  - BACKGROUND: In accordance with the Theory of Structural Dissociation of the
      Personality (TSDP), studies of dissociative identity disorder (DID) have
      documented that two prototypical dissociative subsystems of the personality, the
      "Emotional Part" (EP) and the "Apparently Normal Part" (ANP), have different
      biopsychosocial reactions to supraliminal and subliminal trauma-related cues and
      that these reactions cannot be mimicked by fantasy prone healthy controls nor by
      actors. METHODS: Arterial spin labeling perfusion MRI was used to test the
      hypotheses that ANP and EP in DID have different perfusion patterns in response
      to rest instructions, and that perfusion is different in actors who were
      instructed to simulate ANP and EP. In a follow-up study, regional cerebral blood
      flow of DID patients was compared with the activation pattern of healthy non
      simulating controls. RESULTS: Compared to EP, ANP showed elevated perfusion in
      bilateral thalamus. Compared to ANP, EP had increased perfusion in the
      dorsomedial prefrontal cortex, primary somatosensory cortex, and motor-related
      areas. Perfusion patterns for simulated ANP and EP were different. Fitting their
      reported role-play strategies, the actors activated brain structures involved in
      visual mental imagery and empathizing feelings. The follow-up study demonstrated
      elevated perfusion in the left temporal lobe in DID patients, whereas non
      simulating healthy controls had increased activity in areas which mediate the
      mental construction of past and future episodic events. CONCLUSION: DID involves
      dissociative part-dependent resting-state differences. Compared to ANP, EP
      activated brain structures involved in self-referencing and sensorimotor actions
      more. Actors had different perfusion patterns compared to genuine ANP and EP.
      Comparisons of neural activity for individuals with DID and non-DID simulating
      controls suggest that the resting-state features of ANP and EP in DID are not due
      to imagination. The findings are consistent with TSDP and inconsistent with the
      idea that DID is caused by suggestion, fantasy proneness, and role-playing.

PMID- 24922513
TI  - Stable expression of mtlD gene imparts multiple stress tolerance in finger
      millet.
AB  - Finger millet is susceptible to abiotic stresses, especially drought and salinity
      stress, in the field during seed germination and early stages of seedling
      development. Therefore developing stress tolerant finger millet plants combating
      drought, salinity and associated oxidative stress in these two growth stages is
      important. Cellular protection through osmotic adjustment and efficient free
      radical scavenging ability during abiotic stress are important components of
      stress tolerance mechanisms in plants. Mannitol, an osmolyte, is known to
      scavenge hydroxyl radicals generated during various abiotic stresses and thereby
      minimize stress damage in several plant species. In this study transgenic finger
      millet plants expressing the mannitol biosynthetic pathway gene from bacteria,
      mannitol-1-phosphate dehydrogenase (mtlD), were developed through Agrobacterium
      tumefaciens-mediated genetic transformation. mtlD gene integration in the
      putative transgenic plants was confirmed by Southern blot. Further, performance
      of transgenic finger millet under drought, salinity and oxidative stress was
      studied at plant level in T1 generation and in T1 and T2 generation seedlings.
      Results from these experiments showed that transgenic finger millet had better
      growth under drought and salinity stress compared to wild-type. At plant level,
      transgenic plants showed better osmotic adjustment and chlorophyll retention
      under drought stress compared to the wild-type. However, the overall increase in
      stress tolerance of transgenics for the three stresses, especially for oxidative
      stress, was only marginal compared to other mtlD gene expressing plant species
      reported in the literature. Moreover, the Agrobacterium-mediated genetic
      transformation protocol developed for finger millet in this study can be used to
      introduce diverse traits of agronomic importance in finger millet. 

PMID- 24922514
TI  - Metabolic impact of anti-angiogenic agents on U87 glioma cells.
AB  - BACKGROUND: Glioma cells not only secrete high levels of vascular endothelial
      growth factor (VEGF) but also express VEGF receptors (VEGFR), supporting the
      existence of an autocrine loop. The direct impact on glioma cells metabolism of
      drugs targeting the VEGF pathway, such as Bevacizumab (Bev) or VEGFR Tyrosine
      Kinase Inhibitor (TKI), is poorly known. MATERIAL AND METHODS: U87 cells were
      treated with Bev or SU1498, a selective VEGFR2 TKI. VEGFR expression was checked
      with FACS flow cytometry and Quantitative Real-Time PCR. VEGF secretion into the
      medium was assessed with an ELISA kit. Metabolomic studies on cells were
      performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS).
      RESULTS: U87 cells secreted VEGF and expressed low level of VEGFR2, but no
      detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell
      proliferation and apoptosis. Metabolomic studies with HR MAS showed that Bev had
      no significant effect on cell metabolism, while SU1498 induced a marked increase
      in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of
      lipid droplets was seen in the cytoplasm of SU1498-treated U87 cells. CONCLUSION:
      Although both drugs target the VEGF pathway, only SU1498 showed a clear impact on
      cell proliferation, cell morphology and metabolism. Bevacizumab is thus less
      likely to modify glioma cells phenotype due to a direct therapeutic pressure on
      the VEGF autocrine loop. In patients treated with VEGFR TKI, monitoring lipids
      with magnetic resonance spectroscopic (MRS) might be a valuable marker to assess
      drug cytotoxicity.

PMID- 24922515
TI  - Meeting report: Regulating with RNA in Bacteria 2013.
AB  - On June 4-8, 2013, the 3rd Conference on Regulation with RNA in Bacteria took
      place in Wurzburg, Germany. Following two earlier meetings in Berlin and San
      Juan, this conference has established itself as the primary bi-annual meeting for
      everyone interested in RNA-based regulations in prokaryotes. The 2013 meeting was
      organized by Joel Belasco, Susan Gottesman, Franz Narberhaus, and Jorg Vogel.
      Close to 300 participants from more than 27 countries in Europe, North America,
      and Asia enjoyed four days of talks and posters on many experimental and
      biocomputational aspects of prokaryotic RNA biology. 

PMID- 24922516
TI  - Anti-asialo GM1 NK cell depleting antibody does not alter the development of
      bleomycin induced pulmonary fibrosis.
AB  - Despite circumstantial evidence postulating a protective role for NK cells in
      many fibrotic conditions, their contribution to the development of pulmonary
      fibrosis has yet to be tested. Lung-migrating NK cells are thought to attenuate
      the development of bleomycin induced pulmonary fibrosis (BIPF) by providing anti
      fibrotic mediators and cytokines, such as IFN-gamma. If true, we reasoned that
      depletion of NK cells during experimentally-induced fibrotic disease would lead
      to exacerbated fibrosis. To test this, we treated mice with NK cell-depleting
      antisera (anti-asialo GM1) and evaluated lung inflammation and fibrosis in the
      BIPF model. While NK cell infiltration into the airways was maximal at day 10
      after bleomycin injection, NK cells represented a minor portion (1-3%) of the
      total leukocytes in BAL fluid. Anti-asialo GM1 significantly abrogated NK cell
      numbers over the course of the disease. Depletion of NK cells with anti-asialo
      GM1 before and throughout the BIPF model, or during just the fibrotic phase did
      not alter fibrosis development or affect the levels of any of the pro
      inflammatory/pro-fibrotic cytokines measured (IL-1beta, IL-17, IFN-gamma, TGF
      beta and TNF-alpha). In addition, adoptively transferred NK cells, which were
      detectable systemically and in the airways throughout BIPF, failed to impact lung
      fibrosis. These findings indicate that NK cells likely do not play an essential
      protective role in controlling pulmonary fibrosis development. 

PMID- 24922518
TI  - Circulating mediators of inflammation and immune activation in AIDS-related non
      hodgkin lymphoma.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy
      in developed countries. An elevated risk of developing NHL persists among HIV
      infected individuals in comparison to the general population despite the advent
      of effective antiretroviral therapy. The mechanisms underlying the development of
      AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent
      B-cell activation and inflammation. METHODS: This was a nested case-control study
      within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases
      included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL.
      Controls were matched to each case from among participating HIV-positive males
      who did not develop any malignancy. Matching criteria included time HIV+ or since
      AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum
      biomarkers using multiplexed bead-based immunoassays. RESULTS: A subset of 17
      biomarkers, including cytokines, chemokines, acute phase proteins, tissue
      remodeling agents and bone metabolic mediators was identified to be significantly
      altered in A-NHL cases in comparison to controls. Many of the biomarkers included
      in this subset were positively correlated with HIV viral load. A pathway analysis
      of our results revealed an extensive network of interactions between current and
      previously identified biomarkers. CONCLUSIONS: These findings support the current
      hypothesis that A-NHL develops in the context of persistent immune stimulation
      and inflammation. Further analysis of the biomarkers identified in this report
      should enhance our ability to diagnose, monitor and treat this disease.

PMID- 24922519
TI  - The interplay between the gut microbiota and the immune system.
AB  - The impact of the gut microbiota on immune homeostasis within the gut and,
      importantly, also at systemic sites has gained tremendous research interest over
      the last few years. The intestinal microbiota is an integral component of a
      fascinating ecosystem that interacts with and benefits its host on several
      complex levels to achieve a mutualistic relationship. Host-microbial homeostasis
      involves appropriate immune regulation within the gut mucosa to maintain a
      healthy gut while preventing uncontrolled immune responses against the beneficial
      commensal microbiota potentially leading to chronic inflammatory bowel diseases
      (IBD). Furthermore, recent studies suggest that the microbiota composition might
      impact on the susceptibility to immune-mediated disorders such as autoimmunity
      and allergy. Understanding how the microbiota modulates susceptibility to these
      diseases is an important step toward better prevention or treatment options for
      such diseases. 

PMID- 24922520
TI  - Prognostic value of MET gene copy number and protein expression in patients with
      surgically resected non-small cell lung cancer: a meta-analysis of published
      literatures.
AB  - BACKGROUND: The prognostic value of the copy number (GCN) and protein expression
      of the mesenchymal-epithelial transition (MET) gene for survival of patients with
      non-small cell lung cancer (NSCLC) remains controversial. This study aims to
      comprehensively and quantitatively asses the suitability of MET GCN and protein
      expression to predict patients' survival. METHODS: PubMed, Embase, Web of Science
      and Google Scholar were searched for articles comparing overall survival in
      patients with high MET GCN or protein expression with those with low level.
      Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using
      the random and the fixed-effects models. Subgroup and sensitivity analyses were
      also performed. RESULTS: Eighteen eligible studies enrolling 5,516 patients were
      identified. Pooled analyses revealed that high MET GCN or protein expression was
      associated with poor overall survival (OS) (GCN: HR = 1.90, 95% CI 1.35-2.68,
      p<0.001; protein expression: HR = 1.52, 95% CI 1.08-2.15, p = 0.017). In Asian
      populations (GCN: HR = 2.22, 95% CI 1.46-3.38, p<0.001; protein expression: HR =
      1.89, 95% CI 1.34-2.68, p<0.001), but not in the non-Asian subset. For
      adenocarcinoma, high MET GCN or protein expression indicated decreased OS (GCN:
      HR = 1.49, 95% CI 1.05-2.10, p = 0.025; protein expression: HR = 1.69, 95% CI
      1.31-2.19, p<0.001). Results were similar for multivariate analysis (GCN: HR =
      1.61, 95% CI 1.15-2.25, p = 0.005; protein expression: HR = 2.18, 95% CI 1.60
      2.97, p<0.001). The results of the sensitivity analysis were not materially
      altered and did not draw different conclusions. CONCLUSIONS: Increased MET GCN or
      protein expression was significantly associated with poorer survival in patients
      with surgically resected NSCLC; this information could potentially further
      stratify patients in clinical treatment.

PMID- 24922521
TI  - Comparison of three shortened questionnaires for assessment of quality of life in
      advanced cancer.
AB  - OBJECTIVE: Quality of life (QoL) assessment questionnaires can be burdensome to
      advanced cancer patients, thus necessitating the need for shorter assessment
      instruments than traditionally available. We compare three shortened QoL
      questionnaires in regards to their characteristics, validity, and reliability.
      METHODS: A literature search was conducted to identify studies that employed or
      discussed three abridged QoL questionnaires: the European Organization for
      Research and Treatment of Cancer Quality of Life Core 15-Palliative Care (EORTC
      QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-General-7 (FACT-G7),
      and the Functional Assessment of Chronic Illness Therapy-Palliative Care-14
      (FACIT-PAL-14). Articles that discussed questionnaire length, intended use,
      scoring procedure, and validation were included. RESULTS: The 7-item FACT-G7 is
      the shortest instrument, whereas the EORTC QLQ-C15-PAL and the FACIT-PAL-14
      contain 14 and 15 items, respectively. All three questionnaires have similar
      recall period, item organization, and subscale components. Designed as core
      questionnaires, all three maintain content and concurrent validity of their
      unabridged original questionnaires. Both the EORTC QLQ-C15-PAL and the FACT-G7
      demonstrate good internal consistency and reliability, with Cronbach's alpha
      >=0.7 deemed acceptable. The developmental study for the FACIT-PAL-14 was
      published in 2013 and subsequent validation studies are not yet available.
      CONCLUSION: The EORTC QLQ-C15-PAL and the FACT-G7 were found to be reliable and
      appropriate for assessing health-related QoL issues-the former for palliative
      cancer patients and the latter for advanced cancer patients receiving
      chemotherapy. Conceptually, the FACIT-PAL-14 holds promise to cover social and
      emotional support issues that are not completely addressed by the other two
      questionnaires; however, further validation is needed.

PMID- 24922522
TI  - Graphene oxide-immobilized NH2-terminated silicon nanoparticles by cross-linked
      interactions for highly stable silicon negative electrodes.
AB  - There is a great interest in the utilization of silicon-based anodes for lithium
      ion batteries. However, its poor cycling stability, which is caused by a dramatic
      volume change during lithium-ion intercalation, and intrinsic low electric
      conductivity hamper its industrial applications. A facile strategy is reported
      here to fabricate graphene oxide-immobilized NH2-terminated silicon nanoparticles
      (NPs) negative electrode (Si@NH2/GO) directed by hydrogen bonding and cross
      linked interactions to enhance the capacity retention of the anode. The NH2
      modified Si NPs first form strong hydrogen bonds and covalent bonds with GO. The
      Si@NH2/GO composite further forms hydrogen bonds and covalent bonds with sodium
      alginate, which acts as a binder, to yield a stable composite negative electrode.
      These two chemical cross-linked/hydrogen bonding interactions-one between NH2
      modified Si NPs and GO, and another between the GO and sodium alginate-along with
      highly mechanically flexible graphene oxide, produced a robust network in the
      negative electrode system to stabilize the electrode during discharge and charge
      cycles. The as-prepared Si@NH2/GO electrode exhibits an outstanding capacity
      retention capability and good rate performance, delivering a reversible capacity
      of 1000 mAh g(-1) after 400 cycles at a current of 420 mA g(-1) with almost 100%
      capacity retention. The results indicated the importance of system-level strategy
      for fabricating stable electrodes with improved electrochemical performance. 

PMID- 24922523
TI  - Epithelial cyst of the superior oblique muscle trochlea.
AB  - Most of the congenital orbital cysts are choristomas such as dermoid or
      epidermoid and only in a few cases they are epithelial. Clinically, they manifest
      as cystic movable formations mostly localized in the upper temporal quadrant of
      the orbit. We describe here the case of a 49-year-old man with an orbital cyst
      localized in the upper-nasal quadrant of the orbit and which was showing signs of
      a gradual enlargement and progression over the past weeks. Computed tomography
      revealed a cyst of 1.9 * 1.6 cm in size and located within the trochlea of the
      upper oblique muscle. The cyst was completely extirpated after orbitotomy
      performed by superciliary approach. Histopathology revealed a cyst with
      nonkeratinized cuboidal epithelium. Postoperative course was uneventful, without
      inflammation signs, and after 5 weeks excellent functional and aesthetic effects
      were achieved with no iatrogenic alteration of the ocular motility.

PMID- 24922525
TI  - Structural modifications of mitochondria-targeted chlorambucil alter cell death
      mechanism but preserve MDR evasion.
AB  - Multidrug resistance (MDR) remains one of the major obstacles in chemotherapy,
      potentially rendering a multitude of drugs ineffective. Previously, we have
      demonstrated that mitochondrial targeting of DNA damaging agents is a promising
      tool for evading a number of common resistance factors that are present in the
      nucleus or cytosol. In particular, mitochondria-targeted chlorambucil (mt-Cbl)
      has increased potency and activity against resistant cancer cells compared to the
      parent compound chlorambucil (Cbl). However, it was found that, due to its high
      reactivity, mt-Cbl induces a necrotic type of cell death via rapid nonspecific
      alkylation of mitochondrial proteins. Here, we demonstrate that by tuning the
      alkylating activity of mt-Cbl via chemical modification, the rate of generation
      of protein adducts can be reduced, resulting in a shift of the cell death
      mechanism from necrosis to a more controlled apoptotic pathway. Moreover, we
      demonstrate that all of the modified mt-Cbl compounds effectively evade MDR
      resulting from cytosolic GST-MU upregulation by rapidly accumulating in
      mitochondria, inducing cell death directly from within. In this study, we
      systematically elucidated the advantages and limitations of targeting alkylating
      agents with varying reactivity to mitochondria. 

PMID- 24922524
TI  - Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer's dimer,
      against oxidative-stress-induced cell death in HT22 hippocampal neurons:
      involvement of Nrf2/HO-1 pathway.
AB  - AIMS: Oxidative stress (OS) plays an important role in the pathogenesis of
      neurodegenerative diseases, including Alzheimer's disease (AD). This study was
      designed to uncover the cellular and biochemical mechanisms underlying the
      neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising
      multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death.
      METHODS AND RESULTS: T3CA protected HT22 cells against high-concentration
      glutamate-induced cell death in time- and concentration-dependent manners and
      potently attenuated glutamate-induced intracellular reactive oxygen species (ROS)
      production as well as mitochondrial membrane-potential (DeltaPsi) disruption.
      Besides, T3CA significantly induced nuclear factor erythroid 2-related factor 2
      (Nrf2) nuclear translocation and increased its transcriptional activity, which
      were demonstrated by Western blotting, immunofluorescence, and antioxidant
      response element (ARE)-luciferase reporter gene assay. Further studies showed
      that T3CA potently up-regulated heme oxygenase-1 (HO-1), an endogenous
      antioxidative enzyme and a downstream effector of Nrf2, at both mRNA and protein
      levels. The neuroprotective effects of T3CA were partially reversed by brusatol,
      which reduced protein level of Nrf2, or by inhibiting HO-1 with siRNA or ZnPP-IX,
      a specific inhibitor of HO-1. CONCLUSIONS: Taken together, these results clearly
      demonstrate that T3CA protects neurons against OS-induced cell death partially
      through Nrf2/ARE/HO-1 signaling pathway, which further supports that T3CA might
      be a promising novel therapeutic agent for OS-associated diseases.

PMID- 24922527
TI  - Family income trajectory during childhood is associated with adolescent cigarette
      smoking and alcohol use.
AB  - BACKGROUND: Although childhood socioeconomic disadvantage has been linked with
      adolescent tobacco and alcohol use in cross-sectional research, less is known
      about the influence of changes in socioeconomic status during childhood. Upward
      socioeconomic mobility may attenuate the negative influence of earlier
      socioeconomic disadvantage on health, while downward mobility may counter the
      health benefits of earlier socioeconomic advantage. This study evaluated the
      influence of common trajectories of family income during childhood on smoking and
      alcohol use during adolescence. METHODS: Data utilized were part of the 15-year
      longitudinal Study of Early Child Care and Youth Development. A 5-class
      trajectory model (two stable, one downward, and two upward income trajectories)
      was developed previously with this sample (N=1356). Logistic regression analyses
      were conducted to determine whether children of the more disadvantaged income
      trajectories were more likely to engage in tobacco and alcohol use at age 15
      relative to those of the most advantaged trajectory. RESULTS: Family income
      trajectory was significantly associated with ever-smoking (p=.02) and past-year
      alcohol use at age 15years (p=.008). Children from the less advantaged
      trajectories were more likely to have ever-smoked than children of the most
      advantaged trajectory (all p's<.05). Children of the downwardly mobile trajectory
      were more likely to have used alcohol within the past year than children of the
      most advantaged trajectories as well as the most disadvantaged trajectory (all
      p's<.05). CONCLUSIONS: Findings indicate that childhood socioeconomic
      disadvantage influences adolescent smoking, while downward socioeconomic mobility
      influences adolescent alcohol use.

PMID- 24922517
TI  - Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease is a common debilitating dementia with known
      heritability, for which 20 late onset susceptibility loci have been identified,
      but more remain to be discovered. This study sought to identify new
      susceptibility genes, using an alternative gene-wide analytical approach which
      tests for patterns of association within genes, in the powerful genome-wide
      association dataset of the International Genomics of Alzheimer's Project
      Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and
      48,466 controls. PRINCIPAL FINDINGS: In addition to earlier reported genes, we
      detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4*10-6)
      and 14 (IGHV1-67 p = 7.9*10-8) which indexed novel susceptibility loci.
      SIGNIFICANCE: The additional genes identified in this study, have an array of
      functions previously implicated in Alzheimer's disease, including aspects of
      energy metabolism, protein degradation and the immune system and add further
      weight to these pathways as potential therapeutic targets in Alzheimer's disease.

PMID- 24922528
TI  - The association of puberty and young adolescent alcohol use: do parents have a
      moderating role?
AB  - PURPOSE: To explore the extent to which parent-adolescent emotional closeness,
      family conflict, and parental permissiveness moderate the association of puberty
      and alcohol use in adolescents (aged 10-14). METHODS: Cross-sectional survey of
      7631 adolescents from 231 Australian schools. Measures included pubertal status,
      recent (30day) alcohol use, parent-adolescent emotional closeness, family
      conflict, parental permissiveness of alcohol use and peer alcohol use. The
      analysis was based on a two-level (individuals nested within schools) logistic
      regression model, with main effects entered first, and interaction terms added
      second. RESULTS: The interaction of family factors and pubertal stage did not
      improve the fit of the model, so a main effect model of family factors and
      pubertal stage was adopted. There were significant main effects for pubertal
      stage with boys in middle puberty at increased odds of alcohol use, and girls in
      advanced puberty at increased odds of alcohol use. CONCLUSIONS: Puberty and
      family factors were strong predictors of adolescent alcohol use, but family
      factors did not account for variation in the association of pubertal stage and
      alcohol use.

PMID- 24922529
TI  - Coping style and substance use intention and behavior patterns in a cohort of BC
      adolescents.
AB  - Adolescence is a developmental period during which young teenagers are
      particularly susceptible to shifting from well-defined behavioral intentions to
      abstain from substance use to intentions that include experimentation with
      substance use and in many cases engagement substance use. Coping mechanisms are
      often an important determinant of adolescent well-being, and the style of coping
      adopted by the individual can influence positive or negative health behavior. The
      goal of this study was to examine how the levels of positive coping style (i.e.,
      engagement) and negative coping style (i.e., disengagement) associated with
      increased risk for tobacco and marijuana use, and intentions to use among those
      who have never tried. Higher levels of engagement coping were associated with
      lower odds of tobacco and marijuana use (AOR=0.96 (95% CI: 0.94-0.98), p<0.001
      and AOR=0.95 (95% CI: 0.93-0.97) p<0.001, respectively). Higher levels of
      disengagement coping were associated with greater odds of tobacco and marijuana
      use (AOR=1.03 (95% CI: 1.01-1.05), p<0.001 and AOR=1.05 (95% CI: 1.03-1.07),
      p<0.001, respectively). Engagement coping was also protective against the
      intention to use tobacco (AOR=0.97 (95% CI: 0.96-0.99), p<0.001) or marijuana
      (AOR=0.98 (95% CI: 0.96-0.99), p<0.01). These findings suggest that
      psychoeducational programs supporting the development of engagement oriented
      coping strategies may contribute not only to reductions in adolescents' use of
      tobacco and marijuana, but also to reductions in adolescents' intentions to use
      in the future. 

PMID- 24922526
TI  - Muscle structure influences utrophin expression in mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by
      mutations in the dystrophin gene. To examine the influence of muscle structure on
      the pathogenesis of DMD we generated mdx4cv:desmin double knockout (dko) mice.
      The dko male mice died of apparent cardiorespiratory failure at a median age of
      76 days compared to 609 days for the desmin-/- mice. An ~ 2.5 fold increase in
      utrophin expression in the dko skeletal muscles prevented necrosis in ~ 91% of
      1a, 2a and 2d/x fiber-types. In contrast, utrophin expression was reduced in the
      extrasynaptic sarcolemma of the dko fast 2b fibers leading to increased membrane
      fragility and dystrophic pathology. Despite lacking extrasynaptic utrophin, the
      dko fast 2b fibers were less dystrophic than the mdx4cv fast 2b fibers suggesting
      utrophin-independent mechanisms were also contributing to the reduced dystrophic
      pathology. We found no overt change in the regenerative capacity of muscle stem
      cells when comparing the wild-type, desmin-/-, mdx4cv and dko gastrocnemius
      muscles injured with notexin. Utrophin could form costameric striations with
      alpha-sarcomeric actin in the dko to maintain the integrity of the membrane, but
      the lack of restoration of the NODS (nNOS, alpha-dystrobrevin 1 and 2, alpha1
      syntrophin) complex and desmin coincided with profound changes to the sarcomere
      alignment in the diaphragm, deposition of collagen between the myofibers, and
      impaired diaphragm function. We conclude that the dko mice may provide new
      insights into the structural mechanisms that influence endogenous utrophin
      expression that are pertinent for developing a therapy for DMD.

PMID- 24922530
TI  - Strengths and weaknesses of Global Positioning System (GPS) data-loggers and semi
      structured interviews for capturing fine-scale human mobility: findings from
      Iquitos, Peru.
AB  - Quantifying human mobility has significant consequences for studying physical
      activity, exposure to pathogens, and generating more realistic infectious disease
      models. Location-aware technologies such as Global Positioning System (GPS)
      enabled devices are used increasingly as a gold standard for mobility research.
      The main goal of this observational study was to compare and contrast the
      information obtained through GPS and semi-structured interviews (SSI) to assess
      issues affecting data quality and, ultimately, our ability to measure fine-scale
      human mobility. A total of 160 individuals, ages 7 to 74, from Iquitos, Peru,
      were tracked using GPS data-loggers for 14 days and later interviewed using the
      SSI about places they visited while tracked. A total of 2,047 and 886 places were
      reported in the SSI and identified by GPS, respectively. Differences in the
      concordance between methods occurred by location type, distance threshold (within
      a given radius to be considered a match) selected, GPS data collection frequency
      (i.e., 30, 90 or 150 seconds) and number of GPS points near the SSI place
      considered to define a match. Both methods had perfect concordance identifying
      each participant's house, followed by 80-100% concordance for identifying schools
      and lodgings, and 50-80% concordance for residences and commercial and religious
      locations. As the distance threshold selected increased, the concordance between
      SSI and raw GPS data increased (beyond 20 meters most locations reached their
      maximum concordance). Processing raw GPS data using a signal-clustering algorithm
      decreased overall concordance to 14.3%. The most common causes of discordance as
      described by a sub-sample (n=101) with whom we followed-up were GPS units being
      accidentally off (30%), forgetting or purposely not taking the units when leaving
      home (24.8%), possible barriers to the signal (4.7%) and leaving units home to
      recharge (4.6%). We provide a quantitative assessment of the strengths and
      weaknesses of both methods for capturing fine-scale human mobility.

PMID- 24922531
TI  - Characteristics of myocardial postsystolic shortening in patients with
      symptomatic hypertrophic obstructive cardiomyopathy before and half a year after
      alcohol septal ablation assessed by speckle tracking echocardiography.
AB  - OBJECTIVES: Postsystolic shortening (PSS) has been proposed as a marker of
      myocardial dysfunction. Percutaneous transluminal septal myocardial ablation
      (PTSMA) is an alternative therapy for patients with hypertrophic obstructive
      cardiomyopathy (HOCM) that results in sustained improvements in atrial structure
      and function. We investigated the effects of PTSMA on PSS in HOCM patients using
      speckle tracking imaging. METHODS: Conventional echocardiographic and PSS
      parameters were obtained in 18 healthy controls and 30 HOCM patients before and
      half a year after PTSMA. RESULTS: Compared with the healthy controls, the number
      of segments having PSS and the average value of PSS were significantly increased
      in the HOCM patients. At 6 months after PTSMA, both the number of segments having
      PSS (10.5+/-2.8 vs. 13.2+/-2.6; P<0.001) and the average value of PSS (-1.24+/
      0.57 vs. -1.55+/-0.56; P = 0.009) were significantly reduced. Moreover, the
      reductions in the average value of PSS correlated well with the reductions in the
      E-to-Ea ratio (r = 0.705, P<0.001). CONCLUSIONS: Both the number of segments
      having PSS and the average value of PSS were significantly increased in the HOCM
      patients. PTSMA has a favourable effect on PSS, which may partly account for the
      persistent improvement in LV diastolic function in HOCM patients after PTSMA.

PMID- 24922533
TI  - In Candida parapsilosis the ATC1 gene encodes for an acid trehalase involved in
      trehalose hydrolysis, stress resistance and virulence.
AB  - An ORF named CPAR2-208980 on contig 005809 was identified by screening a Candida
      parapsilosis genome data base. Its 67% identity with the acid trehalase sequence
      from C. albicans (ATC1) led us to designate it CpATC1. Homozygous mutants that
      lack acid trehalase activity were constructed by gene disruption at the two
      CpATC1 chromosomal alleles. Phenotypic characterization showed that atc1Delta
      null cells were unable to grow on exogenous trehalose as carbon source, and also
      displayed higher resistance to environmental challenges, such as saline exposure
      (1.2 M NaCl), heat shock (42 degrees C) and both mild and severe oxidative stress
      (5 and 50 mM H2O2). Significant amounts of intracellular trehalose were
      specifically stored in response to the thermal upshift in both wild type and
      mutant strains. Analysis of their antioxidant activities revealed that catalase
      was only triggered in response to heat shock in atc1Delta cells, whereas
      glutathione reductase was activated upon mild oxidative stress in wild type and
      reintegrant strains, and in response to the whole set of stress treatments in the
      homozygous mutant. Furthermore, yeast cells with double CpATC1 deletion were
      significantly attenuated in non-mammalian infection models, suggesting that
      CpATC1 is required for the pathobiology of the fungus. Our results demonstrate
      the involvement of CpAtc1 protein in the physiological hydrolysis of external
      trehalose in C. parapsilosis, where it also plays a major role in stress
      resistance and virulence. 

PMID- 24922532
TI  - Ubiquitin Specific Protease 26 (USP26) expression analysis in human testicular
      and extragonadal tissues indicates diverse action of USP26 in cell
      differentiation and tumorigenesis.
AB  - Ubiquitin specific protease 26 (USP26), a deubiquitinating enzyme, is highly
      expressed early during murine spermatogenesis, in round spermatids, and at the
      blood-testis barrier. USP26 has also been recognized as a regulator of androgen
      receptor (AR) hormone-induced action involved in spermatogenesis and steroid
      production in in vitro studies. Prior mutation screening of USP26 demonstrated an
      association with human male infertility and low testosterone production, but
      protein localization and expression in the human testis has not been
      characterized previously. USP26 expression analysis of mRNA and protein was
      completed using murine and human testis tissue and human tissue arrays. USP26 and
      AR mRNA levels in human testis were quantitated using multiplex qRT-PCR.
      Immunofluorescence colocalization studies were performed with formalin
      fixed/paraffin-embedded and frozen tissues using primary and secondary antibodies
      to detect USP26 and AR protein expression. Human microarray dot blots were used
      to identify protein expression in extra-gonadal tissues. For the first time,
      expression of USP26 and colocalization of USP26 with androgen receptor in human
      testis has been confirmed predominantly in Leydig cell nuclei, with less in
      Leydig cell cytoplasm, spermatogonia, primary spermatocytes, round spermatids,
      and Sertoli cells. USP26 likely affects regulatory proteins of early
      spermatogenesis, including androgen receptor with additional activity in round
      spermatids. This X-linked gene is not testis-specific, with USP26 mRNA and
      protein expression identified in multiple other human organ tissues (benign and
      malignant) including androgen-dependent tissues such as breast (myoepithelial
      cells and secretory luminal cells) and thyroid tissue (follicular cells).
      USP26/AR expression and interaction in spermatogenesis and androgen-dependent
      cancer warrants additional study and may prove useful in diagnosis and management
      of male infertility. 

PMID- 24922534
TI  - Clinical features and course of ocular toxocariasis in adults.
AB  - PURPOSE: To investigate the clinical features, clinical course of granuloma,
      serologic findings, treatment outcome, and probable infection sources in adult
      patients with ocular toxocariasis (OT). METHODS: In this retrospective cohort
      study, we examined 101 adult patients diagnosed clinically and serologically with
      OT. Serial fundus photographs and spectral domain optical coherence tomography
      images of all the patients were reviewed. A clinic-based case-control study on
      pet ownership, occupation, and raw meat ingestion history was performed to
      investigate the possible infection sources. RESULTS: Among the patients diagnosed
      clinically and serologically with OT, 69.6% showed elevated immunoglobulin E
      (IgE) levels. Granuloma in OT involved all retinal layers and several
      vitreoretinal comorbidities were noted depending on the location of granuloma:
      posterior pole granuloma was associated with epiretinal membrane and retinal
      nerve fiber layer defects, whereas peripheral granuloma was associated with
      vitreous opacity. Intraocular migration of granuloma was observed in 15 of 93
      patients (16.1%). Treatment with albendazole (400 mg twice a day for 2 weeks) and
      corticosteroids (oral prednisolone; 0.5-1 mg/kg/day) resulted in comparable
      outcomes to patients on corticosteroid monotherapy; however, the 6-month
      recurrence rate in patients treated with combined therapy (17.4%) was
      significantly lower than that in patients treated with corticosteroid monotherapy
      (54.5%, P=0.045). Ingestion of raw cow liver (80.8%) or meat (71.2%) was
      significantly more common in OT patients than healthy controls. CONCLUSIONS: Our
      study discusses the diagnosis, treatment, and prevention strategies for OT.
      Evaluation of total IgE, in addition to anti-toxocara antibody, can assist in the
      serologic diagnosis of OT. Combined albendazole and corticosteroid therapy may
      reduce intraocular inflammation and recurrence. Migrating feature of granuloma is
      clinically important and may further suggest the diagnosis of OT. Clinicians need
      to carefully examine comorbid conditions for OT. OT may be associated with
      ingestion of uncooked meat, especially raw cow liver, in adult patients.

PMID- 24922536
TI  - Protein conservation and variation suggest mechanisms of cell type-specific
      modulation of signaling pathways.
AB  - Many proteins and signaling pathways are present in most cell types and tissues
      and yet perform specialized functions. To elucidate mechanisms by which these
      ubiquitous pathways are modulated, we overlaid information about cross-cell line
      protein abundance and variability, and evolutionary conservation onto functional
      pathway components and topological layers in the pathway hierarchy. We found that
      the input (receptors) and the output (transcription factors) layers evolve more
      rapidly than proteins in the intermediary transmission layer. In contrast,
      protein expression variability decreases from the input to the output layer. We
      observed that the differences in protein variability between the input and
      transmission layer can be attributed to both the network position and the
      tendency of variable proteins to physically interact with constitutively
      expressed proteins. Differences in protein expression variability and
      conservation are also accompanied by the tendency of conserved and constitutively
      expressed proteins to acquire somatic mutations, while germline mutations tend to
      occur in cell type-specific proteins. Thus, conserved core proteins in the
      transmission layer could perform a fundamental role in most cell types and are
      therefore less tolerant to germline mutations. In summary, we propose that the
      core signal transmission machinery is largely modulated by a variable input layer
      through physical protein interactions. We hypothesize that the bow-tie
      organization of cellular signaling on the level of protein abundance variability
      contributes to the specificity of the signal response in different cell types. 

PMID- 24922537
TI  - Thermogenesis, flowering and the association with variation in floral odour
      attractants in Magnolia sprengeri (Magnoliaceae).
AB  - Magnolia sprengeri Pamp. is an ornamentally and ecologically important tree that
      blooms at cold temperatures in early spring. In this study, thermogenesis and
      variation in the chemical compounds of floral odours and insect visitation in
      relation to flowering cycles were studied to increase our understanding of the
      role of floral thermogenesis in the pollination biology of M. sprengeri. There
      were five distinct floral stages across the floral cycle of this species: pre
      pistillate, pistillate, pre-staminate, staminate and post-staminate. Floral
      thermogenesis during anthesis and consisted of two distinct peaks: one at the
      pistillate stage and the other at the staminate stage. Insects of five families
      visited M. sprengeri during the floral cycle, and sap beetles (Epuraea sp.,
      Nitidulidae) were determined to be the most effective pollinators, whereas bees
      (Apis cerana, Apidae) were considered to be occasional pollinators. A strong
      fragrance was released during thermogenesis, consisting of 18 chemical compounds.
      Although the relative proportions of these compounds varied at different floral
      stages across anthesis, linalool, 1-iodo-2-methylundecane and 2,2,6-trimethyl-6
      vinyltetrahydro-2H-pyran-3-ol were dominant. Importantly, we found that the
      floral blends released during the pistillate and staminate stages were very
      similar, and coincided with flower visitation by sap beetles and the two
      thermogenic episodes. Based on these results, we propose that odour acts as a
      signal for a reward (pollen) and that an odour mimicry of staminate-stage flowers
      occurs during the pistillate stage. 

PMID- 24922538
TI  - Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based
      on quinoxaline scaffold.
AB  - In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of
      new quinoxaline-based derivatives was designed and synthesized. The target
      compounds were biologically evaluated for their inhibitory activity against VEGFR
      2. The design of the target compounds was accomplished after a profound study of
      the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among
      the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3-oxo-3,4
      dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory
      activity against VEGFR-2. Molecular modeling study involving molecular docking
      and field alignment was implemented to interpret the variable inhibitory activity
      of the newly synthesized compounds. 

PMID- 24922539
TI  - A highly sensitive NADH sensor based on a mycelium-like nanocomposite using
      graphene oxide and multi-walled carbon nanotubes to co-immobilize poly(luminol)
      and poly(neutral red) hybrid films.
AB  - Hybridization of poly(luminol) (PLM) and poly(neutral red) (PNR) has been
      successfully performed and further enhanced by a conductive and steric hybrid
      nanotemplate using graphene oxide (GO) and multi-walled carbon nanotubes
      (MWCNTs). The morphology of the PLM-PNR-MWCNT-GO mycelium-like nanocomposite is
      studied by SEM and AFM and it is found to be electroactive, pH-dependent, and
      stable in the electrochemical system. It shows electrocatalytic activity towards
      NADH with a high current response and low overpotential. Using amperometry, it
      has been shown to have a high sensitivity of 288.9 MUA mM(-1) cm(-2) to NADH
      (Eapp. = +0.1 V). Linearity is estimated in a concentration range of 1.33 * 10(
      8) to 1.95 * 10(-4) M with a detection limit of 1.33 * 10(-8) M (S/N = 3).
      Particularly, it also shows another linear range of 2.08 * 10(-4) to 5.81 * 10(
      4) M with a sensitivity of 151.3 MUA mM(-1) cm(-2). The hybridization and
      activity of PLM and PNR can be effectively enhanced by MWCNTs and GO, resulting
      in an active hybrid nanocomposite for determination of NADH. 

PMID- 24922540
TI  - Genetic determinants of long-term changes in blood lipid concentrations: 10-year
      follow-up of the GLACIER study.
AB  - Recent genome-wide meta-analyses identified 157 loci associated with cross
      sectional lipid traits. Here we tested whether these loci associate (singly and
      in trait-specific genetic risk scores [GRS]) with longitudinal changes in total
      cholesterol (TC) and triglyceride (TG) levels in a population-based prospective
      cohort from Northern Sweden (the GLACIER Study). We sought replication in a
      southern Swedish cohort (the MDC Study; N = 2,943). GLACIER Study participants (N
      = 6,064) were genotyped with the MetaboChip array. Up to 3,495 participants had
      10-yr follow-up data available in the GLACIER Study. The TC- and TG-specific GRSs
      were strongly associated with change in lipid levels (beta = 0.02 mmol/l per
      effect allele per decade follow-up, P = 2.0 * 10(-11) for TC; beta = 0.02 mmol/l
      per effect allele per decade follow-up, P = 5.0 * 10(-5) for TG). In individual
      SNP analysis, one TC locus, apolipoprotein E (APOE) rs4420638 (beta = 0.12 mmol/l
      per effect allele per decade follow-up, P = 2.0 * 10(-5)), and two TG loci,
      tribbles pseudokinase 1 (TRIB1) rs2954029 (beta = 0.09 mmol/l per effect allele
      per decade follow-up, P = 5.1 * 10(-4)) and apolipoprotein A-I (APOA1) rs6589564
      (beta = 0.31 mmol/l per effect allele per decade follow-up, P = 1.4 * 10(-8)),
      remained significantly associated with longitudinal changes for the respective
      traits after correction for multiple testing. An additional 12 loci were
      nominally associated with TC or TG changes. In replication analyses, the APOE
      rs4420638, TRIB1 rs2954029, and APOA1 rs6589564 associations were confirmed (P <=
      0.001). In summary, trait-specific GRSs are robustly associated with 10-yr
      changes in lipid levels and three individual SNPs were strongly associated with
      10-yr changes in lipid levels.

PMID- 24922541
TI  - Modeling the spread of multiple concurrent contagions on networks.
AB  - Many contagions spread over various types of communication networks and their
      spreading dynamics have been extensively studied in the literature. Here we
      propose a general model for the concurrent spread of an arbitrary number of
      contagions in complex networks. The model is stochastic and runs in discrete
      time, and includes two widely used mechanisms by which a node can change its
      state. The first, termed the spontaneous state change mechanism, describes
      spontaneous transition to another state, while the second, termed the contact
      induced state change mechanism, describes acquiring other contagions due to
      contact with the neighbors. We consider reactive discrete-time spreading
      processes of multiple concurrent contagions where time steps are of finite size
      without neglecting the possibility of multiple infecting events in a single time
      step. An essential element for making the model numerically tractable is the use
      of an approximation for the probability that a node transits to a specific state
      given any set of neighboring states. Different transmission probabilities may be
      present between each pair of states. We also derive corresponding continuous-time
      equations that are simple and intuitive. The model includes many well-known
      epidemic and rumor spreading models as a special case and it naturally captures
      spreading processes in multiplex networks. 

PMID- 24922542
TI  - Computational and experimental study on the electrocatalytic reduction of CO2 to
      CO by a new mononuclear ruthenium(ii) complex.
AB  - A new mononuclear ruthenium(ii) complex, trans-[Ru(dmb)2(Cl)(EtOH)](PF6) (dmb =
      4,4'-dimethyl-2,2'-bipyridine), has been prepared and characterized by elemental
      analysis, spectroscopic techniques and single crystal X-ray structure
      determination. The complex was studied as a precatalyst for the electrocatalytic
      reduction of CO2 to CO in an acetonitrile solution by cyclic voltammetry (CV).
      The catalytic mechanism was investigated by means of quantum chemical
      calculations to gain deeper insight into the process of CO2 reduction. The
      results suggest that the reaction proceeds in six steps initiating by the two
      sequential 1e reductions at the dmb ligands followed by CO2 addition to give a
      metallocarboxylate intermediate. This intermediate undergoes further reduction
      and loses a CO molecule. The results reported in this paper are of great
      significance in providing theoretical insight into a class of electrocatalysts
      for reduction of CO2 to CO. 

PMID- 24922543
TI  - Tricyclic pyrazoles. Part 6. Benzofuro[3,2-c]pyrazole: a versatile architecture
      for CB2 selective ligands.
AB  - A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The
      novel compounds (15-24) were evaluated for their affinity to CB2 and CB1
      cannabinoid receptors. The synthesis of the title compounds takes advantage of
      the acid-catalysed thermal cyclization of bicyclic hydrazone ethyl 2-(2-(2,4
      dichlorophenyl)hydrazono)-2-(6-methyl-3-oxo-2,3-dihydrobenzofuran-2-yl)acetate to
      tricyclic ethyl 1-(2,4-dichlorophenyl)-6-methyl-1H-benzofuro[3,2-c]pyrazol-3
      carboxylate. All the obtained derivatives showed high affinity to CB2 receptors.
      Moreover, significant selectivity for CB2 over CB1 receptors was highlighted for
      lead derivatives amongst the novel series. The best binding profiles were
      determined for homologues bearing monocyclic and bicyclic monoterpenic
      substituents at the carbamoyl group at 3 position of the pyrazole ring (KiCB2 < 4
      nM). In particular, the isopinocampheyl-substituted derivative 22 exhibited the
      highest selectivity for CB2 receptors with Ki values of 3.7 and 2398 nM for CB2
      and CB1 receptors, respectively. Preliminary functional assays evidenced CB2
      agonism behaviour for all the assayed novel derivatives.

PMID- 24922544
TI  - Discovery and characterization of novel imidazopyridine derivative CHEQ-2 as a
      potent CDC25 inhibitor and promising anticancer drug candidate.
AB  - Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle
      transition and proliferation via the interactions with CDK/Cyclin complexes.
      Overexpression of CDC25 proteins is frequently observed in cancer and is related
      to aggressiveness, high-grade tumors and poor prognosis. Thus, inhibiting CDC25
      activity in cancer treatment appears a good therapeutic strategy. In this
      article, refinement of the initial hit XDW-1 by synthesis and screening of a
      focused compound library led to the identification of a novel set of
      imidazopyridine derivatives as potent CDC25 inhibitors. Among them, the most
      potent molecule was CHEQ-2, which could efficiently inhibit the activities of
      CDC25A/B enzymes as well as the proliferation of various different types of
      cancer cell lines in vitro assay. Moreover, CHEQ-2 triggered S-phase cell cycle
      arrest in MCF-7, HepG2 and HT-29 cell lines, accompanied by generation of ROS,
      mitochondrial dysfunction and apoptosis. Besides, oral administration of CHEQ-2
      (10 mg/kg) significantly inhibited xenografted human liver tumor growth in nude
      mice, while demonstrated extremely low toxicity (LD50 > 2000 mg/kg). These
      findings make CHEQ-2 a good starting point for further investigation and
      structure modification.

PMID- 24922545
TI  - Supraclavicular skin temperature as a measure of 18F-FDG uptake by BAT in human
      subjects.
AB  - BACKGROUND: Brown adipose tissue (BAT) has emerged as a novel player in energy
      homeostasis in humans and is considered a potential new target for combating
      obesity and related diseases. The current 'gold standard' for quantification of
      BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of
      this technique is limited by cost and radiation exposure. Given the fact that BAT
      is a thermogenic tissue, mainly located in the supraclavicular region, the aim of
      the current study was to investigate whether cold-induced supraclavicular skin
      temperature and core body temperature may be alternative markers of BAT
      activation in humans. SUBJECTS/METHODS: BAT volume and activity were measured in
      24 healthy lean adolescent males (mean age 24.1+/-0.8 years), using cold-induced
      18F-FDG uptake with PET-CT. Core body temperature was measured continuously in
      the small intestine with use of an ingestible telemetric capsule and skin
      temperature was measured by eighteen wireless iButtons attached to the skin
      following ISO-defined locations. RESULTS: Proximal and distal (hand/feet) skin
      temperatures markedly decreased upon cold exposure, while supraclavicular skin
      temperature significantly increased (35.2+/-0.1 vs. 35.5+/-0.1 degrees C, p =
      0.001). Furthermore, cold-induced supraclavicular skin temperature positively
      correlated with both total (R2 = 0.28, P = 0.010) and clavicular BAT volume (R2 =
      0.20, P = 0.030) and clavicular SUVmax (R2 = 0.27, P = 0.010), while core body
      temperature did not. CONCLUSIONS: Supraclavicular skin temperature as measured by
      iButtons may have predictive value for BAT detection in adult humans. This is
      highly desirable considering the increasing interest in pharmacological
      interventions to stimulate BAT in human subjects. TRIAL REGISTRATION: NTR 2473.

PMID- 24922547
TI  - You are what you eat.
AB  - Gut bacteria is now considered as an additional host organ, and it has been shown
      that they have important influences on host developmental and physiological
      processes. More recently gut bacteria have additionally been implicated in
      behavioral processes. We showed that in two species of Drosophila, gut bacteria
      variation affects behavior, altering partner investment in copulation in relation
      to whether individuals were familiar (i.e., having developed in the same
      environment), or were related. This suggests that gut bacteria play a role in kin
      recognition in these species. We suggest that this phenomenon is associated with
      gut bacteria influencing the scent profiles used by Drosophila in mate choice. 

PMID- 24922546
TI  - Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle development.
AB  - The essential role of autophagy in muscle homeostasis has been clearly
      demonstrated by phenotype analysis of mice with muscle-specific inactivation of
      genes encoding autophagy-related proteins. Ambra1 is a key component of the
      Beclin 1 complex and, in zebrafish, it is encoded by two paralogous genes,
      ambra1a and ambra1b, both required for normal embryogenesis and larval
      development. In this study we focused on the function of Ambra1, a positive
      regulator of the autophagic process, during skeletal muscle development by means
      of morpholino (MO)-mediated knockdown and compared the phenotype of zebrafish
      Ambra1-depleted embryos with that of Ambra1gt/gt mouse embryos. Morphological
      analysis of zebrafish morphant embryos revealed that silencing of ambra1 impairs
      locomotor activity and muscle development, as well as myoD1 expression. Skeletal
      muscles in ATG-morphant embryos displayed severe histopathological changes and
      contained only small areas of organized myofibrils that were widely dispersed
      throughout the cell. Double knockdown of ambra1a and ambra1b resulted in a more
      severe phenotype whereas defects were much less evident in splice-morphants. The
      morphants phenotypes were effectively rescued by co-injection with human AMBRA1
      mRNA. Together, these results indicate that ambra1a and ambra1b are required for
      the correct development and morphogenesis of skeletal muscle. 

PMID- 24922548
TI  - Convergence analysis of evolutionary algorithms that are based on the paradigm of
      information geometry.
AB  - The convergence behaviors of so-called natural evolution strategies (NES) and of
      the information-geometric optimization (IGO) approach are considered. After a
      review of the NES/IGO ideas, which are based on information geometry, the
      implications of this philosophy w.r.t. optimization dynamics are investigated
      considering the optimization performance on the class of positive quadratic
      objective functions (the ellipsoid model). Exact differential equations
      describing the approach to the optimizer are derived and solved. It is rigorously
      shown that the original NES philosophy optimizing the expected value of the
      objective functions leads to very slow (i.e., sublinear) convergence toward the
      optimizer. This is the real reason why state of the art implementations of IGO
      algorithms optimize the expected value of transformed objective functions, for
      example, by utility functions based on ranking. It is shown that these utility
      functions are localized fitness functions that change during the IGO flow. The
      governing differential equations describing this flow are derived. In the case of
      convergence, the solutions to these equations exhibit an exponentially fast
      approach to the optimizer (i.e., linear convergence order). Furthermore, it is
      proven that the IGO philosophy leads to an adaptation of the covariance matrix
      that equals in the asymptotic limit-up to a scalar factor-the inverse of the
      Hessian of the objective function considered. 

PMID- 24922550
TI  - Early experience with multiparametric magnetic resonance imaging-targeted
      biopsies under visual transrectal ultrasound guidance in patients suspicious for
      prostate cancer undergoing repeated biopsy.
AB  - OBJECTIVES: The purpose of this study was to investigate the detection rate of
      prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted
      biopsies (mp-MRI-bx) in patients with prior negative transrectal ultrasound
      biopsy (TRUS-bx) sessions without previous experience of this. MATERIAL AND
      METHODS: Eighty-three patients with prior negative TRUS-bx scheduled for repeated
      biopsies due to persistent suspicion of PCa were prospectively enrolled. mp-MRI
      was performed before biopsy and all lesions were scored according to the Prostate
      Imaging Reporting and Data System (PI-RADS) and Likert classification. All
      underwent repeated TRUS-bx (10 cores) and mp-MRI-bx under visual TRUS guidance of
      any mp-MRI-suspicious lesion not targeted by systematic TRUS-bx. RESULTS: PCa was
      found in 39 out of 83 patients (47%) and mp-MRI identified at least one lesion
      with some degree of suspicion in all 39 patients. Both PI-RADS and Likert scoring
      showed a high correlation between suspicion of malignancy and biopsy results (p <
      0.0001). Five patients (13%) had cancer detected only on mp-MRI-bx outside the
      TRUS-bx areas (p = 0.025) and another seven patients (21%) had an overall Gleason
      score upgrade of at least one grade based on the mp-MRI-bx. Secondary PCa lesions
      not visible on mp-MRI were detected by TRUS-bx in six out of 39 PCa patients. The
      secondary foci were all Gleason 6 (3 + 3) in 5-10% of the biopsy core. According
      to the Epstein criteria, 37 out of 39 cancer patients were classified as
      clinically significant. CONCLUSION: Using mp-MRI, even without previous
      experience, can improve the detection rate of significant PCa at repeated biopsy
      and allows more accurate Gleason grading.

PMID- 24922549
TI  - Rat middle cerebral artery occlusion is not a suitable model for the study of
      stroke-induced spontaneous infections.
AB  - BACKGROUND: Infections related to stroke-induced immunodepression are an
      important complication causing a high rate of death in patients. Several
      experimental studies in mouse stroke models have described this process but it
      has never been tested in other species such as rats. METHODS: Our study focused
      on the appearance of secondary systemic and pulmonary infections in ischemic
      rats, comparing with sham and naive animals. For that purpose, male Wistar rats
      were subjected to embolic middle cerebral artery occlusion (eMCAO) or to
      transient MCAO (tMCAO) inserting a nylon filament. Forty-eight hours after
      ischemia, blood and lung samples were evaluated. RESULTS: In eMCAO set, ischemic
      rats showed a significant decrease in blood-peripheral lymphocytes (naive =
      58.8+/-18.1%, ischemic = 22.9+/-16.4%) together with an increase in
      polymorphonuclears (PMNs) (naive = 29.2+/-14.7%, ischemic = 71.7+/-19.5%), while
      no change in monocytes was observed. The increase in PMNs counts was positively
      correlated with worse neurological outcome 48 hours after eMCAO (r = 0.55, p =
      0.043). However, sham animals showed similar changes in peripheral leukocytes as
      those seen in ischemic rats (lymphocytes: 40.1+/-19.7%; PMNs: 51.7+/-19.2%).
      Analysis of bacteriological lung growth showed clear differences between naive
      (0+/-0 CFU/mL; log10) and both sham (3.9+/-2.5 CFU/mL; log10) and ischemic (4.3+/
      2.9 CFU/mL; log10) groups. Additionally, naive animals presented non-pathological
      lung histology, while both sham and ischemic showed congestion, edema or
      hemorrhage. Concordant results were found in the second set of animals submitted
      to a tMCAO. CONCLUSIONS: Inflammatory and infection changes in Wistar rats
      subjected to MCAO models may be attributed not only to the brain ischemic injury
      but to the surgical aggression and/or anaesthetic stress. Consequently, we
      suggest that stroke-induced immunodepression in ischemic experimental models
      should be interpreted with caution in further experimental and translational
      studies, at least in rat stroke models that entail cervicotomy and cranial
      trepanation.

PMID- 24922552
TI  - Preliminary thermoluminescence and optically stimulated luminescence
      investigation of commercial pharmaceutical preparations towards the drug
      sterilization dosimetry.
AB  - Drug sterilization with ionizing radiation is a well-established technology and
      is gaining ground the last decades due to its numerous advantages. Identification
      of irradiated drugs would be interesting and, in this respect, the present work
      aims, for the first time to the authors' best knowledge, to explore whether OSL
      and TL can be employed as methods for post-sterilization dosimetry on commercial
      drugs, i.e., as tools for the detection of irradiated drugs. Five widely used
      drugs, i.e., Daktarin((r)), Aspirin((r)), Panadol((r)), Brufen((r)) and
      Procef((r)), are used for this purpose. Preliminary findings are very promising
      towards the post-sterilization dosimetry and the use of commercial drugs for
      normal and/or accidental dosimetry. 

PMID- 24922551
TI  - Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of
      placental extract, exhibits synergistic antioxidant activity in the presence of
      estradiol.
AB  - Placenta, as a reservoir of nutrients, has been widely used in medical and
      cosmetic materials. Here, we focused on the antioxidant properties of placental
      extract and attempted to isolate and identify the main antioxidant factors.
      Porcine placental extracts were prepared through homogenization or acid
      hydrolysis, and their antioxidant activity was investigated in the human
      keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE)
      increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE
      treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased
      intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in
      H-PE were found to be thermo-unstable and were thus expected to include proteins.
      The candidate antioxidant proteins were fractionated with cation-exchange, anion
      exchange, and size-exclusion chromatography, and the antioxidant properties of
      the chromatographic fractions were investigated. We obtained specific antioxidant
      fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From
      silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was
      identified as a main marker for the antioxidant effect of H-PE. Purified AFP or
      ectopically expressed AFP exhibited synergistic antioxidant activity in the
      presence of estradiol. Taken together, our data suggest that AFP, a serum
      glycoprotein produced at high levels during fetal development, is a novel marker
      protein for the antioxidant effect of the placenta that exhibits synergistic
      antioxidant activity in the presence of estradiol. 

PMID- 24922553
TI  - 68Ge content quality control of 68Ge/68Ga-generator eluates and 68Ga
      radiopharmaceuticals--a protocol for determining the 68Ge content using thin
      layer chromatography.
AB  - (68)Ge breakthrough from a (68)Ge/(68)Ga-generator appears to be one of the most
      critical parameters for the routine clinical application of this generator and
      (68)Ga-radiopharmaceuticals. We report a TLC-based (thin-layer chromatography)
      protocol which allows the (68)Ge breakthrough of a generator to be determined
      within 1 h post-initial elution. The protocol can also be adapted to allow the
      (68)Ge content of a (68)Ga-radiopharmaceutical preparation to be determined prior
      to in vivo application.

PMID- 24922554
TI  - Determination of full-energy peak efficiency at the center position of a through
      hole-type clover detector between 0.05 MeV and 3.2 MeV by source measurements and
      Monte Carlo simulations.
AB  - Full-energy peak efficiency at the center position of a through-hole-type clover
      detector was determined by the measurement of standard sources and by Monte Carlo
      simulation. The coincidence summing under the large-solid-angle condition was
      corrected using Monte Carlo calculation based on the specific decay scheme for
      (133)Ba, (152,154)Eu, and (56)Co. This allowed the peak efficiency to be extended
      from 0.05 MeV to 3.2 MeV with an approximate uncertainty of 3%.

PMID- 24922555
TI  - Type 2 diabetes in pregnancy: Rates of fetal malformations and level of
      preconception care.
AB  - An observational study was performed to assess the prevalence of fetal
      malformations and the level of preconception care in women with Type 2 diabetes.
      Pregnant women with Type 2 diabetes who delivered between 2002 and 2010 were
      recruited to the study. The fetal malformation rate of patients with Type 2
      diabetes was compared with the rate in a control group; the general population.
      The malformation rate was 3.2 (7.2-2.2%; p < 0.0001) greater in the diabetes
      group. In addition, only 4% of women with Type 2 diabetes had preconception care.
      Despite evidence of benefits in women receiving preconception care, patients with
      Type 2 diabetes do not attend for preconception counselling and the malformation
      rate is high.

PMID- 24922556
TI  - Cross-interference of plant development and plant-microbe interactions.
AB  - Plant roots are host to a multitude of filamentous microorganisms. Among these,
      arbuscular mycorrhizal fungi provide benefits to plants, while pathogens trigger
      diseases resulting in significant crop yield losses. It is therefore imperative
      to study processes which allow plants to discriminate detrimental and beneficial
      interactions in order to protect crops from diseases while retaining the ability
      for sustainable bio-fertilisation strategies. Accumulating evidence suggests that
      some symbiosis processes also affect plant-pathogen interactions. A large part of
      this overlap likely constitutes plant developmental processes. Moreover, microbes
      utilise effector proteins to interfere with plant development. Here we list
      relevant recent findings on how plant-microbe interactions intersect with plant
      development and highlight future research leads. 

PMID- 24922557
TI  - Image and surgery-related costs comparing cone beam CT and panoramic imaging
      before removal of impacted mandibular third molars.
AB  - OBJECTIVES: The aim of this prospective clinical study was to derive the absolute
      and relative costs of cone beam CT (CBCT) and panoramic imaging before removal of
      an impacted mandibular third molar. Furthermore, the study aimed to analyse the
      influence of different cost-setting scenarios on the outcome of the absolute and
      relative costs and the incremental costs related to surgery. METHODS: A
      randomized clinical trial compared complications following surgical removal of a
      mandibular third molar, where the pre-operative diagnostic method had been
      panoramic imaging or CBCT. The resources implied in the two methods were measured
      with health economic tools. The primary outcome was total costs defined as the
      sum of absolute imaging costs and incremental surgery-related costs. The basic
      variables were capital costs, operational costs, radiological costs, radiographic
      costs, overheads and patient resource utilization. Differences in resources used
      for surgical and post-surgical management were calculated for each patient.
      RESULTS: Converted to monetary units, the total costs for panoramic imaging
      equalized ?49.29 and for CBCT examination ?184.44. Modifying effects on this
      outcome such as differences in surgery time, treatment time for complications,
      pre- and post-surgical medication, sickness absence, specialist treatment and
      hospitalization were not statistically significant between the two diagnostic
      method groups. CONCLUSIONS: Costs for a CBCT examination were approximately four
      times the costs for panoramic imaging when used prior to removal of a mandibular
      third molar. The use of CBCT did not change the resources used for surgery, post
      surgical treatment and patient complication management.

PMID- 24922558
TI  - Theoretical study of the photochemical initiation in nitroxide-mediated
      photopolymerization.
AB  - Nitroxide-mediated photopolymerization (NMP(2)) is a promising novel route to
      initiate radical polymerization. In NMP(2), alkoxyamines bounded to a monomer are
      attached to a chromophore. Upon light absorption, the excitation energy is
      transferred from the chromophore to the alkoxyamine moiety, inducing the cleavage
      of the oxygen-carbon bond and thus initiating the polymerization. The NMP(2)
      mechanism depends strongly on several factors like the type of chromophore, the
      monomer, the connectivity pattern, etc. This complexity makes it difficult to
      design new NMP(2) initiators with increased polymerization efficiency and
      selectivity. In the present article, we characterize by means of quantum
      mechanical calculations the main steps of the NMP(2) initiation for alkoxyamines
      attached to aromatic ketones. We show how the excitation energy can be
      transferred from the chromophore to the alkoxyamine moiety, and present two
      easily computed parameters which can account for the selectivity of the O-C bond
      photocleaveage. Finally, using results obtained for a series of isomers, we give
      some rules that may help the design of more efficient NMP(2) initiators. 

PMID- 24922559
TI  - Use of angular vessels in head and neck free-tissue transfer: a comprehensive
      preclinical evaluation.
AB  - IMPORTANCE: The angular artery, its perforating branches, and their zones of
      tissue perfusion have been described extensively for facial reconstruction.
      Various cutaneous and mucosal flaps with either anterograde or retrograde
      perfusion play an important role in facial and oral reconstruction. However,
      these flaps share the limitations of pedicled nature and donor-site intolerance.
      Free-tissue transfer (FTT) has transformed capabilities and outcomes in head and
      neck reconstruction. While less constrained by tissue volume and subtype, FTT has
      its own limitations, including pedicle reach for anastomosis to inflow and
      outflow vasculature in upper face reconstruction. The angular vessels, owing to
      their relatively high central location and accessibility via a camouflaged
      nasolabial fold incision, may have value in midface and nasal reconstruction.
      OBJECTIVES: To detail a technique for consistently locating the angular vessels
      while preserving the integrity of adjacent neuromuscular structures and to
      evaluate the caliber and consistency of the angular artery and vein for their
      usability in microvascular anastomosis. DESIGN AND SETTING: We conducted a PubMed
      literature search for the terms angular artery, melolabial flap, nasolabial flap,
      retroangular flap, and any associations with FTT. We also performed 26 anatomic
      cadaveric dissections on 13 fresh cadavers to evaluate the angular arteries and
      veins. MAIN OUTCOMES AND MEASURES: Vessel caliber, length, and variability were
      analyzed and utility for use in FTT was assessed. A total of 26 angular arteries
      and 26 angular veins were included in the analysis. Anatomic relationships were
      used to develop a surgical schema for dissection and isolation of the angular
      vessels specifically for FTT. RESULTS: The angular vessels have consistent
      anatomic relationships facilitating localization and have a consistent caliber
      amenable to use in microvascular FTT. The mean (SD) artery diameter was 2.34
      (0.67) mm prior to dilation and 3.21 (0.87) mm after dilation. The diameters of
      the vein before and after dilation were 3.57 (0.53) mm and 6.40 (0.81) mm,
      respectively. There was no statistical difference between the vessels on the
      right and left sides. CONCLUSIONS AND RELEVANCE: We describe for the first time
      the anatomic cadaveric dissection and analysis of the angular arteries and veins
      specifically to determine compatibility with regard to FTT. We found good FTT
      compatibility. LEVEL OF EVIDENCE: NA.

PMID- 24922560
TI  - Process induced electroactive beta-polymorph in PVDF: effect on dielectric and
      ferroelectric properties.
AB  - The effects of various processing conditions, like annealing, poling, mechanical
      rolling and their combinations, on the dielectric and ferroelectric properties of
      PVDF [poly(vinylidene fluoride)] were systematically studied in this work.
      Further, the effect of processing sequence on the structure and properties was
      investigated. While all the processing conditions adopted here resulted in phase
      transformation of the alpha- to electroactive beta-polymorph in PVDF, the
      fraction of beta-phase developed was observed to be strongly contingent on the
      adopted process. The transformation of alpha to electroactive beta-polymorph was
      determined by X-ray diffraction and FTIR. The neat PVDF showed only alpha-phase,
      whereas mechanically rolled samples exhibited the highest ca. 85% beta-phase in
      PVDF. Both the permittivity and the loss tangent decreased in the samples which
      had undergone different processing conditions. The polarization-electric field (P
      E) loops for all the samples were evaluated. Interestingly, the energy density,
      estimated from the electrical displacement-electric field (D-E) loops, was
      observed to be highest for the poled samples which were initially rolled. The
      results indicate that various processing conditions can influence the dielectric
      and the ferroelectric properties differently. 

PMID- 24922561
TI  - Multicenter cohort study to assess the impact of a silver-alloy and hydrogel
      coated urinary catheter on symptomatic catheter-associated urinary tract
      infections.
AB  - PURPOSE: The purpose of this study was to determine the effect of a silver-alloy
      hydrogel catheter on symptomatic catheter-associated urinary tract infections
      (CAUTIs). DESIGN: Multicenter before-after non-randomized cohort study. SUBJECTS
      AND SETTING: Seven acute care hospitals ranging in size from 124 to 607 beds
      participated in this study. The study population included adult patients with a
      positive urine culture 2 or more days after admission, who underwent Foley
      catheterization. METHODS: Catheter-associated urinary tract infection
      surveillance was conducted at each hospital for at least 3 months during the use
      of a standard catheter and 3 months during the use of the silver-alloy hydrogel
      catheter. Both the National Healthcare Safety Network (NHSN) surveillance and a
      clinical definition of CAUTI were used for rate calculation. RESULTS: A 47%
      relative reduction in the CAUTI rate was observed with the silver-alloy hydrogel
      catheter compared to the standard catheter when both infection definitions were
      used (0.945/1000 patient days vs 0.498/1000 patient days) (odds ratio = 0.53; P <
      .0001; 95% CI: 0.45-0.62). When only NHSN-defined CAUTIs were considered, a 58%
      relative reduction occurred in the silver-alloy hydrogel period (0.60/1000
      patient days vs 0.25/1000 patient days) (odds ratio = 0.42; P < .0001; 95% CI:
      0.34-0.53). Antimicrobial days for CAUTIs decreased from 1165 (standard catheter
      period) to 406 (silver-alloy hydrogel period). CONCLUSIONS: Use of a silver-alloy
      hydrogel urinary catheter reduced symptomatic CAUTI occurrences as defined by
      both NHSN and clinical criteria.

PMID- 24922562
TI  - Study of active duty military for pulmonary disease related to environmental
      deployment exposures (STAMPEDE).
AB  - RATIONALE: Because of increased levels of airborne particulate matter in
      Southwest Asia, deployed military personnel are at risk for developing acute and
      chronic lung diseases. Increased respiratory symptoms are reported, but limited
      data exist on reported lung diseases. OBJECTIVES: To evaluate new respiratory
      complaints in military personnel returning from Southwest Asia to determine
      potential etiologies for symptoms. METHODS: Returning military personnel
      underwent a prospective standardized evaluation for deployment-related
      respiratory symptoms within 6 months of returning to their duty station.
      MEASUREMENTS AND MAIN RESULTS: Prospective standardized evaluation included full
      pulmonary function testing, high-resolution chest tomography, methacholine
      challenge testing, and fiberoptic bronchoscopy with bronchoalveolar lavage. Other
      procedures including lung biopsy were performed if clinically indicated. Fifty
      patients completed the study procedures. A large percentage (42%) remained
      undiagnosed, including 12% with normal testing and an isolated increase in lavage
      neutrophils or lymphocytes. Twenty (40%) patients demonstrated some evidence of
      airway hyperreactivity to include eight who met asthma criteria and two with
      findings secondary to gastroesophageal reflux. Four (8%) additional patients had
      isolated reduced diffusing capacity and the remaining six had other miscellaneous
      airway disorders. No patients were identified with diffuse parenchymal disease on
      the basis of computed tomography imaging. A significant number (66%) of this
      cohort had underlying mental health and sleep disorders. CONCLUSIONS: Evaluation
      of new respiratory symptoms in military personnel after service in Southwest Asia
      should focus on airway hyperreactivity from exposures to higher levels of ambient
      particulate matter. These patients may be difficult to diagnose and require close
      follow-up.

PMID- 24922563
TI  - Investigations of the intermolecular forces between RDX and polyethylene by force
      distance spectroscopy and molecular dynamics simulations.
AB  - The development of novel nanoenergetic materials with enhanced bulk properties
      requires an understanding of the intermolecular interactions occurring between
      molecular components. We investigate the surface interactions between 1,3,5
      trinitro-1,3,5-triazacyclohexane (RDX) and polyethylene (PE) crystals on the
      basis of combined use of molecular dynamics (MD) simulations and force-distance
      spectroscopy, in conjunction with Lifshitz macroscopic theory of van der Waals
      forces between continuous materials. The binding energy in the RDX-PE system
      depends both on the degree of PE crystallinity and on the RDX crystal face. Our
      MD simulations yield binding energies of approximately 132 and 120 mJ/m(2) for
      100% amorphous and 100% crystalline PE on RDX (210), respectively. The average
      value is about 36% greater than our experimental value of 81 +/- 15 mJ/m(2) for
      PE (~48% amorphous) on RDX (210). By comparison, Liftshitz theory predicts a
      value of about 79 mJ/m(2) for PE interacting with RDX. Our MD simulations also
      predict larger binding energies for both amorphous and crystalline PE on RDX
      (210) compared to the RDX (001) surface. Analysis of the interaction potential
      indicates that about 60% of the binding energy in the PE-RDX system is due to
      attractive interactions between HPE-ORDX and CPE-NRDX pairs of atoms. Further,
      amorphous PE shows a much longer interaction distance than crystalline PE with
      the (210) and (001) RDX surfaces due to the possibility of larger polymer
      elongations in the case of amorphous PE as strain is applied. Also, we report
      estimates of the binding energies of energetic materials RDX and octahydro
      1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) with PE, propylene, polystyrene, and
      several fluorine-containing polymers using Lifshitz theory and compare these with
      reported MD calculations. 

PMID- 24922564
TI  - The superelastic mechanism of Si3N4 microsprings using micro-Raman spectroscopy.
AB  - Silicon nitride microsprings with superelasticity are characterized using SEM,
      XRD, TEM and micro-Raman methods. The internal structure and the superelastic
      mechanism of silicon nitride microsprings are proposed through analyzing the
      variation of Raman peaks upon stretching gradually. During the stretching
      process, since all the vibrations are internal vibrations within the primitive
      unit cell, the basic structure has no changes and the residual stress never
      concentrates. The special structure of the fine grains and no sharp grain
      boundaries make the silicon nitride microsprings possess such good superelastic
      properties. 

PMID- 24922565
TI  - Influenza viruses en route from birds to man.
AB  - Human and other mammalian influenza viruses emerge from a large gene pool
      provided by avian influenza viruses. Two recent studies (Watanabe et al., 2014;
      Linster et al., 2014) show that adaptation to a mammalian host depends on a
      limited number of mutations that allow airborne transmission, a specific trait of
      the mammalian viruses.

PMID- 24922566
TI  - Toward an activist agenda for monitoring virus emergence.
AB  - The continuing emergence of arboviruses such as chikungunya virus requires
      thoughtful attention and approaches for risk management. Incorporating
      experimental evolutionary studies, as described in this issue by Stapleford et
      al. (2014), has the potential to move public health toward a more proactive
      agenda for predicting and responding to disease emergence.

PMID- 24922567
TI  - Antigen smuggling in tuberculosis.
AB  - The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well
      established; however, how dendritic cells activate T cells in vivo remains
      obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report
      a mechanism of antigen transfer for efficient activation of antimycobacterial T
      cells.

PMID- 24922568
TI  - Nod-like receptors have a grip on stem cells.
AB  - Two reports in this issue of Cell Host & Microbe establish that Nod-like receptor
      proteins NOD1 and NOD2 regulate stem cell function. Burberry et al. (2014)
      demonstrate that NOD1 and NOD2 synergize with TLRs to mobilize hematopoietic stem
      cells. Nigro et al. (2014) report that NOD2 provides cytoprotection to intestinal
      stem cells.

PMID- 24922569
TI  - Exploring new horizons in microbiome research.
AB  - Leading scientists in microbiome research met at Lake Titisee, Germany, in April
      2014 to discuss the current state of the field, the most urgent and unresolved
      questions, state-of-the-art technological advances, and new avenues of future
      research. We summarize some of the concepts and themes discussed at this meeting.

PMID- 24922570
TI  - Advances in norovirus biology.
AB  - Human noroviruses are a major cause of epidemic and sporadic gastroenteritis
      worldwide and can chronically infect immunocompromised patients. Efforts to
      develop effective vaccines and antivirals have been hindered by the uncultivable
      nature and extreme genetic diversity of human noroviruses. Although they remain a
      particularly challenging pathogen to study, recent advances in norovirus animal
      models and in vitro cultivation systems have led to an increased understanding of
      norovirus molecular biology and replication, pathogenesis, cell tropism, and
      innate and adaptive immunity. Furthermore, clinical trials of vaccines consisting
      of nonreplicating virus-like particles have shown promise. In this review, we
      summarize these recent advances and discuss controversies in the field, which is
      rapidly progressing toward generation of antiviral agents and increasingly
      effective vaccines.

PMID- 24922571
TI  - The Nogo receptor NgR1 mediates infection by mammalian reovirus.
AB  - Neurotropic viruses, including mammalian reovirus, must disseminate from an
      initial site of replication to the central nervous system (CNS), often binding
      multiple receptors to facilitate systemic spread. Reovirus engages junctional
      adhesion molecule A (JAM-A) to disseminate hematogenously. However, JAM-A is
      dispensable for reovirus replication in the CNS. We demonstrate that reovirus
      binds Nogo receptor NgR1, a leucine-rich repeat protein expressed in the CNS, to
      infect neurons. Expression of NgR1 confers reovirus binding and infection of
      nonsusceptible cells. Incubating reovirus virions with soluble NgR1 neutralizes
      infectivity. Blocking NgR1 on transfected cells or primary cortical neurons
      abrogates reovirus infection. Concordantly, reovirus infection is ablated in
      primary cortical neurons derived from NgR1 null mice. Reovirus virions bind to
      soluble JAM-A and NgR1, while infectious disassembly intermediates (ISVPs) bind
      only to JAM-A. These results suggest that reovirus uses different capsid
      components to bind distinct cell-surface molecules, engaging independent
      receptors to facilitate spread and tropism. 

PMID- 24922573
TI  - Emergence and transmission of arbovirus evolutionary intermediates with epidemic
      potential.
AB  - The high replication and mutation rates of RNA viruses can result in the
      emergence of new epidemic variants. Thus, the ability to follow host-specific
      evolutionary trajectories of viruses is essential to predict and prevent
      epidemics. By studying the spatial and temporal evolution of chikungunya virus
      during natural transmission between mosquitoes and mammals, we have identified
      viral evolutionary intermediates prior to emergence. Analysis of virus
      populations at anatomical barriers revealed that the mosquito midgut and salivary
      gland pose population bottlenecks. By focusing on virus subpopulations in the
      saliva of multiple mosquito strains, we recapitulated the emergence of a recent
      epidemic strain of chikungunya and identified E1 glycoprotein mutations with
      potential to emerge in the future. These mutations confer fitness advantages in
      mosquito and mammalian hosts by altering virion stability and fusogenic activity.
      Thus, virus evolutionary trajectories can be predicted and studied in the short
      term before new variants displace currently circulating strains.

PMID- 24922572
TI  - Circulating avian influenza viruses closely related to the 1918 virus have
      pandemic potential.
AB  - Wild birds harbor a large gene pool of influenza A viruses that have the
      potential to cause influenza pandemics. Foreseeing and understanding this
      potential is important for effective surveillance. Our phylogenetic and
      geographic analyses revealed the global prevalence of avian influenza virus genes
      whose proteins differ only a few amino acids from the 1918 pandemic influenza
      virus, suggesting that 1918-like pandemic viruses may emerge in the future. To
      assess this risk, we generated and characterized a virus composed of avian
      influenza viral segments with high homology to the 1918 virus. This virus
      exhibited pathogenicity in mice and ferrets higher than that in an authentic
      avian influenza virus. Further, acquisition of seven amino acid substitutions in
      the viral polymerases and the hemagglutinin surface glycoprotein conferred
      respiratory droplet transmission to the 1918-like avian virus in ferrets,
      demonstrating that contemporary avian influenza viruses with 1918 virus-like
      proteins may have pandemic potential.

PMID- 24922574
TI  - A cell-intrinsic inhibitor of HIV-1 reverse transcription in CD4(+) T cells from
      elite controllers.
AB  - HIV-1 reverse transcription represents the predominant target for pharmacological
      inhibition of viral replication, but cell-intrinsic mechanisms that can block HIV
      1 reverse transcription in a clinically significant way are poorly defined. We
      find that effective HIV-1 reverse transcription depends on the phosphorylation of
      viral reverse transcriptase by host cyclin-dependent kinase (CDK) 2 at a highly
      conserved Threonine residue. CDK2-dependent phosphorylation increased the
      efficacy and stability of viral reverse transcriptase and enhanced viral fitness.
      Interestingly, p21, a cell-intrinsic CDK inhibitor that is upregulated in CD4(+)
      T cells from "elite controllers," potently inhibited CDK2-dependent
      phosphorylation of HIV-1 reverse transcriptase and significantly reduced the
      efficacy of viral reverse transcription. These data suggest that p21 can
      indirectly block HIV-1 reverse transcription by inhibiting host cofactors
      supporting HIV-1 replication and identify sites of viral vulnerability that are
      effectively targeted in persons with natural control of HIV-1 replication.

PMID- 24922575
TI  - The classical lancefield antigen of group a Streptococcus is a virulence
      determinant with implications for vaccine design.
AB  - Group A Streptococcus (GAS) is a leading cause of infection-related mortality in
      humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC),
      comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine
      (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological
      function has been attributed to this conserved antigen. Here we identify and
      characterize the GAC biosynthesis genes, gacA through gacL. An isogenic mutant of
      the glycosyltransferase gacI, which is defective for GlcNAc side-chain addition,
      is attenuated for virulence in two infection models, in association with
      increased sensitivity to neutrophil killing, platelet-derived antimicrobials in
      serum, and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC
      lacking the GlcNAc side chain and containing only polyrhamnose promoted
      opsonophagocytic killing of multiple GAS serotypes and protected against systemic
      GAS challenge after passive immunization. Thus, the Lancefield antigen plays a
      functional role in GAS pathogenesis, and a deeper understanding of this unique
      polysaccharide has implications for vaccine development.

PMID- 24922576
TI  - Cell-to-cell transfer of M. tuberculosis antigens optimizes CD4 T cell priming.
AB  - During Mycobacterium tuberculosis and other respiratory infections, optimal T
      cell activation requires pathogen transport from the lung to a local draining
      lymph node (LN). However, the infected inflammatory monocyte-derived dendritic
      cells (DCs) that transport M. tuberculosis to the local lymph node are relatively
      inefficient at activating CD4 T cells, possibly due to bacterial inhibition of
      antigen presentation. We found that infected migratory DCs release M.
      tuberculosis antigens as soluble, unprocessed proteins for uptake and
      presentation by uninfected resident lymph node DCs. This transfer of bacterial
      proteins from migratory to local DCs results in optimal priming of antigen
      specific CD4 T cells, which are essential in controlling tuberculosis.
      Additionally, this mechanism does not involve transfer of the whole bacterium and
      is distinct from apoptosis or exosome shedding. These findings reveal a mechanism
      that bypasses pathogen inhibition of antigen presentation by infected cells and
      generates CD4 T cell responses that control the infection.

PMID- 24922577
TI  - The DNA damage-regulated autophagy modulator DRAM1 links mycobacterial
      recognition via TLR-MYD88 to autophagic defense [corrected].
AB  - Autophagy is an important defense mechanism against mycobacteria, the causative
      agents of tuberculosis. The molecular mechanisms that link mycobacterial
      recognition to autophagy remain unclear. Our analysis in zebrafish and human
      macrophage models of mycobacterial infection reveals that the DNA damage
      regulated autophagy modulator DRAM1 functions downstream of pathogen recognition
      by the Toll-like receptor (TLR)/interleukin-1 receptor (IL1R)-MYD88-NF-kappaB
      innate immune sensing pathway to activate selective autophagy. Mycobacterial
      infection of human macrophages and zebrafish embryos induced DRAM1 expression in
      a MYD88 and NF-kappaB-dependent manner. DRAM1 knockdown increased mycobacterial
      infection, whereas overexpression lowered infection by hyperactivating autophagy.
      DRAM1-mediated selective autophagic defenses require the cytosolic DNA sensor
      STING and the selective autophagy receptor p62/SQSTM1. Contrary to its known role
      in autophagy-mediated cell death and cancer, this DRAM1 function is p53
      independent. We propose that DRAM1 mediates autophagic defense against a broader
      range of intracellular pathogens, since DRAM1 expression was also induced by the
      common bacterial endotoxin lipopolysaccharide.

PMID- 24922579
TI  - Photochemical and microbial alterations of DOM spectroscopic properties in the
      estuarine system Ria de Aveiro.
AB  - The influence of photochemical transformations of chromophoric dissolved organic
      matter (CDOM) on microbial communities was evaluated in the estuarine system Ria
      de Aveiro. Two sites, representative of the marine and brackish water zones of
      the estuary, were surveyed regularly in order to determine seasonal and vertical
      profiles of variation of CDOM properties. Optical parameters of CDOM indicative
      of aromaticity and molecular weight were used to establish CDOM sources, and
      microbial abundance and activity was characterized. Additionally, microcosm
      experiments were performed in order to simulate photochemical reactions of CDOM
      and to evaluate microbial responses to light-induced changes in CDOM composition.
      The CDOM of the two estuarine zones showed different spectral characteristics,
      with significantly higher values of the specific ultra-violet absorbance at 254
      nm (SUVA254) (5.5 times) and of the absorption coefficient at 350 nm (a350) (12
      times) and lower SR (S275-295/S350-400) ratio at brackish water compared with the
      marine zone, reflecting the different amounts and prevailing sources of organic
      matter, as well as distinct riverine and oceanic influences. At the marine zone,
      the abundance of bacteria and the activity of Leu-AMPase correlated with a350 and
      a254, suggesting a microbial contribution to the HMW CDOM pool. The irradiation
      of DOM resulted in a decrease of the values of a254 and a350 and an increase of
      the slope S275-295 and of the ratios E2 : E3 (a250/a365) and SR, which in turn
      increase its bioavailability. However, the extent of photoinduced transformations
      and microbial responses was dependent on the initial optical characteristics of
      CDOM. In Ria de Aveiro both photochemical and microbial processes yielded optical
      changes in CDOM and the overall results of these combined processes determine the
      fate of CDOM in the estuarine system and have an influence on local productivity
      and in adjacent coastal areas. 

PMID- 24922578
TI  - Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple
      bacterial clearance from inflammation and promote dysbiosis.
AB  - Certain low-abundance bacterial species, such as the periodontitis-associated
      oral bacterium Porphyromonas gingivalis, can subvert host immunity to remodel a
      normally symbiotic microbiota into a dysbiotic, disease-provoking state. However,
      such pathogens also exploit inflammation to thrive in dysbiotic conditions. How
      these bacteria evade immunity while maintaining inflammation is unclear. As
      previously reported, P. gingivalis remodels the oral microbiota into a dysbiotic
      state by exploiting complement. Now we show that in neutrophils P. gingivalis
      disarms a host-protective TLR2-MyD88 pathway via proteasomal degradation of
      MyD88, whereas it activates an alternate TLR2-Mal-PI3K pathway. This alternate
      TLR2-Mal-PI3K pathway blocks phagocytosis, provides "bystander" protection to
      otherwise susceptible bacteria, and promotes dysbiotic inflammation in vivo. This
      mechanism to disengage bacterial clearance from inflammation required an intimate
      crosstalk between TLR2 and the complement receptor C5aR and can contribute to the
      persistence of microbial communities that drive dysbiotic diseases.

PMID- 24922580
TI  - Hydration of bilayered graphene oxide.
AB  - The hydration of graphene oxide (GO) membranes is the key to understand their
      remarkable selectivity in permeation of water molecules and humidity-dependent
      gas separation. We investigated the hydration of single GO layers as a function
      of humidity using scanning force microscopy, and we determined the single
      interlayer distance from the step height of a single GO layer on top of one or
      two GO layers. This interlayer distance grows gradually by approximately 1 A upon
      a relative humidity (RH) increase in the range of 2 to ~80%, and the immersion
      into liquid water increases the interlayer distance further by another 3 A. The
      gradual expansion of the single interlayer distance is in good agreement with the
      averaged distance measured by X-ray diffraction on multilayered graphite oxides,
      which is commonly explained with an interstratification model. However, our
      experimental design excludes effects connected to interstratification. Instead we
      determine directly if insertion of water into GO occurs strictly by monolayers or
      the thickness of GO layers changes gradually. We find that hydration with up to
      80% RH is a continuous process of incorporation of water molecules into single GO
      layers, while liquid water inserts as monolayers. The similarity of hydration for
      our bilayer and previously reported multilayered materials implies GO few and
      even bilayers to be suitable for selective water transport.

PMID- 24922581
TI  - Enantioselective nucleophile-catalyzed synthesis of tertiary alkyl fluorides via
      the alpha-fluorination of ketenes: synthetic and mechanistic studies.
AB  - The catalytic asymmetric synthesis of alkyl fluorides, particularly alpha
      fluorocarbonyl compounds, has been the focus of substantial effort in recent
      years. While significant progress has been described in the formation of
      enantioenriched secondary alkyl fluorides, advances in the generation of tertiary
      alkyl fluorides have been more limited. Here, we describe a method for the
      catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N
      fluorodibenzenesulfonimide (NFSI) and C6F5ONa to furnish tertiary alpha
      fluoroesters. Mechanistic studies are consistent with the hypothesis that the
      addition of an external nucleophile (C6F5ONa) is critical for turnover, releasing
      the catalyst (PPY*) from an N-acylated intermediate. The available data can be
      explained by a reaction pathway wherein the enantioselectivity is determined in
      the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived
      from the addition of PPY* to the ketene. The structure and the reactivity of the
      product of this proposed elementary step, an alpha-fluoro-N-acylpyridinium salt,
      have been examined. 

PMID- 24922582
TI  - Catalytic degradation of dye molecules and in situ SERS monitoring by peroxidase
      like Au/CuS composite.
AB  - In this paper, Au/CuS composites were fabricated by a two-step method based on a
      facile solvothermal approach combined with the in situ reduction. It was
      demonstrated that the Au/CuS composite not only exhibited excellent peroxidase
      like catalytic activity in the oxidation of the typical peroxidases (o
      phenylenediamine and diaminobenzidine), but also showed promising SERS
      performance with remarkable sensitivity and high reproducibility. Based on these
      properties, the bi-functional Au/CuS composite was employed both as a catalyst
      for degrading a pollutant (Rhodamine 6G) and a SERS substrate for real-time
      monitoring of the degradation process quantitatively. 

PMID- 24922583
TI  - Optimization of 6-heterocyclic-2-(1H-pyrazol-1-yl)-N-(pyridin-2-yl)pyrimidin-4
      amine as potent adenosine A2A receptor antagonists for the treatment of
      Parkinson's disease.
AB  - Parkinson's disease is a neurodegenerative disease characterized by the motor
      symptoms of bradykinesia, tremor, and rigidity. Current therapies are based
      mainly on dopaminergic replacement strategies by administration of either
      dopamine agonists or dopamine precursor levodopa (L-Dopa). These treatments
      provide symptomatic relief without slowing or stopping the disease progression,
      and long-term usage of these drugs is associated with diminished efficacy, motor
      fluctuation, and dyskinisia. Unfortunately, there had been few novel treatments
      developed in the past decades. Among nondopaminergic strategies for the treatment
      of Parkinson's disease, antagonism of the adenosine A2A receptor has emerged to
      show great potential. Here we report the optimization of a new chemical scaffold,
      which achieved exceptional receptor binding affinity and ligand efficiency
      against adenosine A2A receptor. The leading compounds demonstrated excellent
      efficacy in the haloperidol induced catalepsy model for Parkinson's disease. 

PMID- 24922584
TI  - The role of social support on resilience, posttraumatic growth, hopelessness, and
      depression among children of HIV-infected parents in mainland China.
AB  - Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has a
      profound impact not only on the infected individuals, but also on their families.
      Children of the HIV-infected parents are particularly affected. The present study
      examined the relationship between social support, resilience, posttraumatic
      growth (PTG), hopelessness, and depression among 195 children of HIV-infected
      parents in mainland China. Results showed that 35.4% of the sample scored above
      the cutoff of the Children's Depression Inventory. Results from structural
      equation modeling reported that social support had a significant positive
      relationship with resilience and PTG. Higher levels of resilience and PTG were
      associated with lower level of hopelessness which in turn, was associated with
      lower level of depression. The overall model achieved satisfactory fit.
      Interventions are needed to improve social support of the children affected by
      HIV so as to improve their mental health.

PMID- 24922586
TI  - Fibroblast signal transducer and activator of transcription 4 drives cigarette
      smoke-induced airway fibrosis.
AB  - Cigarette smoke-induced emphysema and small airway remodeling are the anatomic
      bases of chronic obstructive pulmonary disease (COPD), but the pathogenesis of
      these changes is unclear, and current treatments for COPD are minimally
      effective. To evaluate the role of signal transducer and activator of
      transcription (STAT)-4 in cigarette smoke-induced small airway remodeling, we
      used C57BL/6J (wild type [WT]) and STAT4-/- mice exposed to air or cigarette
      smoke for 6 months and isolated airway and parenchymal fibroblasts. We also
      compared the results with those obtained with human fibroblasts. We found that
      STAT4-/- mice were protected against smoke-induced small airway remodeling but
      not emphysema. STAT4 is abundantly expressed in airway compared with parenchymal
      derived fibroblasts isolated from normal human and murine lung. WT airway
      fibroblasts proliferate faster than STAT4-/- airway fibroblasts, whereas there is
      no difference between strains for parenchymal fibroblasts. IL-12 is up-regulated
      in the lung after smoke exposure, and IL-12 receptor B2 is expressed on airway
      and parenchymal fibroblasts in mouse and human lung. Treatment with IL-12 causes
      phosphorylation of STAT4 in WT airway fibroblasts. Exposure of WT airway, but not
      parenchymal, fibroblasts to IL-12 causes increased expression of collagen 1alpha1
      and transforming growth factor beta1, factors involved in small airway
      remodeling, whereas STAT4-/- fibroblasts are unresponsive to IL-12. These results
      indicate that IL-12 can drive small airway remodeling via STAT4 signaling and
      suggest that treatment with clinically available anti-IL-12p40 drugs might
      provide a new approach to preventing small airway remodeling in cigarette
      smokers. 

PMID- 24922585
TI  - Activity and architecture of pyroglutamate-modified amyloid-beta (AbetapE3-42)
      pores.
AB  - Among the family of Abeta peptides, pyroglutamate-modified Abeta (AbetapE)
      peptides are particularly associated with cytotoxicity in Alzheimer's disease
      (AD). They represent the dominant fraction of Abeta oligomers in the brains of AD
      patients, but their accumulation in the brains of elderly individuals with normal
      cognition is significantly lower. Accumulation of AbetapE plaques precedes the
      formation of plaques of full-length Abeta (Abeta1-40/42). Most of these
      properties appear to be associated with the higher hydrophobicity of AbetapE as
      well as an increased resistance to enzymatic degradation. However, the important
      question of whether AbetapE peptides induce pore activity in lipid membranes and
      their potential toxicity compared with other Abeta pores is still open. Here we
      examine the activity of AbetapE pores in anionic membranes using planar bilayer
      electrical recording and provide their structures using molecular dynamics
      simulations. We find that AbetapE pores spontaneously induce ionic current across
      the membrane and have some similar properties to the other previously studied
      pores of the Abeta family. However, there are also some significant differences.
      The onset of AbetapE3-42 pore activity is generally delayed compared with Abeta1
      42 pores. However, once formed, AbetapE3-42 pores produce increased ion
      permeability of the membrane, as indicated by a greater occurrence of higher
      conductance electrical events. Structurally, the lactam ring of AbetapE peptides
      induces a change in the conformation of the N-terminal strands of the AbetapE3-42
      pores. While the N-termini of wild-type Abeta1-42 peptides normally reside in the
      bulk water region, the N-termini of AbetapE3-42 peptides tend to reside in the
      hydrophobic lipid core. These studies provide a first step to an understanding of
      the enhanced toxicity attributed to AbetapE peptides. 

PMID- 24922588
TI  - Development of an adverse outcome pathway for acetylcholinesterase inhibition
      leading to acute mortality.
AB  - Adverse outcome pathways (AOPs) are designed to describe linkages of key events
      within a biological pathway that result in an adverse outcome associated with
      chemical perturbation of a well-defined molecular initiating event. Risk
      assessors have traditionally relied on data from apical endpoints (e.g.,
      mortality, growth, reproduction) to derive benchmark values for use in
      determining the potential adverse impacts of chemicals. One goal in building
      reliable and well-characterized AOPs is to identify relevant in vitro assays
      and/or in vivo biomarkers that could be used in screening the potential hazard of
      substances, thereby reducing costs and increasing the number of chemicals that
      can be evaluated in a timely fashion. The purpose of this review article is to
      build an AOP for substances with a molecular initiating event of
      acetylcholinesterase inhibition leading to acute mortality following guidance
      developed by the Organisation for Economic Cooperation and Development. In
      contrast to most other AOPs developed to date, in which coverage is for a
      relatively limited taxonomic group or life stage, this AOP is applicable to a
      wide range of species at multiple life stages. Furthermore, while development of
      most AOPs has relied on data for a few model chemicals, the AOP described in the
      present review captures information from a large number of studies with a
      diversity of organophosphate and carbamate insecticides.

PMID- 24922587
TI  - Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7
      carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as
      poly(ADP-ribose)polymerase-1 inhibitors.
AB  - Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and
      2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide)
      derivatives were synthesized and evaluated as inhibitors of poly(ADP
      ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead
      compound 3 (DHBF-7-carboxamide; IC50 = 9.45 MUM). To facilitate synthetically
      feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide
      (36, IC50 = 16.2 MUM). The electrophilic 2-position of this scaffold was
      accessible for extended modifications. Substituted benzylidene derivatives at the
      2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58
      (IC50 = 0.531 MUM) showing a 30-fold improvement in potency. Various heterocycles
      attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in
      significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68,
      70, 72, and 73; IC50 values from 0.718 to 0.079 MUM). Compound 66 showed
      selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three
      inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1
      structure were obtained, providing insights into further development of these
      inhibitors.

PMID- 24922589
TI  - Chitosan coated polylactic acid nanoparticle-mediated combinatorial delivery of
      cisplatin and siRNA/Plasmid DNA chemosensitizes cisplatin-resistant human ovarian
      cancer cells.
AB  - Development of resistance toward anticancer drugs results in ineffective therapy
      leading to increased mortality. Therefore, overriding resistance and restoring
      sensitivity to anticancer drugs will improve treatment efficacy and reduce
      mortality. While numerous mechanisms for drug resistance in cancer have
      previously been demonstrated, recent studies implicate a role for proteasome and
      the autophagy regulatory protein P62/SQSTM1 (P62) in contributing to drug
      resistance. Specifically, reduction in the expression of the beta5 subunit of the
      proteasome and/or enhanced P62 protein expression is known to contribute to
      cancer drug resistance such as cisplatin (CDDP) in ovarian cancer cells.
      Therefore, we hypothesized that restoration of beta5 expression and/or
      suppression of P62 protein expression in CDDP-resistant ovarian cancer cells will
      lead to restoration of sensitivity to CDDP and enhanced cell killing. To test our
      hypothesis we developed a biodegradable multifunctional nanoparticle (MNP) system
      that codelivered P62siRNA, beta5 plasmid DNA, and CDDP and tested its efficacy in
      CDDP resistant 2008/C13 ovarian cancer cells. MNP consisted of CDDP loaded
      polylactic acid nanoparticle as inner core and cationic chitosan (CS) consisting
      of ionically linked P62siRNA (siP62) and/or beta5 expressing plasmid DNA (pbeta5)
      as the outer layer. The MNPs were spherical in shape with a hydrodynamic diameter
      in the range of 280-350 nm, and demonstrated encapsulation efficiencies of 82%
      and 78.5% for CDDP and siRNA respectively. MNPs efficiently protected the siRNA
      and showed superior serum stability compared to naked siRNA as measured by gel
      retardation and spectrophotometry assays. The MNPs successfully delivered siP62
      and pbeta5 to cause P62 knockdown and restoration of beta5 expression in 2008/C13
      cells. Combined delivery of siP62, pbeta5, and CDDP using the MNPs resulted in a
      marked reduction in the IC50 value of CDDP in 2008/C13 cells from 125 +/- 1.3 MUM
      to 98 +/- 0.6 MUM (P < 0.05; 21.6% reduction) when compared to the reduction in
      the IC50 of CDDP observed in cells that had only siP62 delivered (IC50 = 106 +/-
      1.1 MUM; P < 0.05; 15.2% reduction) or pbeta5 delivered (IC50 = 115 +/- 2.8 MUM;
      8% reduction) via MNPs. Finally, our studies showed that the CDDP resistance
      index in 2008/C13 cells was reduced from 4.62 for free CDDP to 3.62 for MNP
      treatment. In conclusion our study results demonstrated the efficacy of our MNP
      in overcoming CDDP resistance in ovarian cancer cells. 

PMID- 24922590
TI  - Feasibility of detecting prostate cancer by ultraperformance liquid
      chromatography-mass spectrometry serum metabolomics.
AB  - Prostate cancer (PCa) is the second leading cause of cancer-related mortality in
      men. The prevalent diagnosis method is based on the serum prostate-specific
      antigen (PSA) screening test, which suffers from low specificity, overdiagnosis,
      and overtreatment. In this work, untargeted metabolomic profiling of age-matched
      serum samples from prostate cancer patients and healthy individuals was performed
      using ultraperformance liquid chromatography coupled to high-resolution tandem
      mass spectrometry (UPLC-MS/MS) and machine learning methods. A metabolite-based
      in vitro diagnostic multivariate index assay (IVDMIA) was developed to predict
      the presence of PCa in serum samples with high classification sensitivity,
      specificity, and accuracy. A panel of 40 metabolic spectral features was found to
      be differential with 92.1% sensitivity, 94.3% specificity, and 93.0% accuracy.
      The performance of the IVDMIA was higher than the prevalent PSA test. Within the
      discriminant panel, 31 metabolites were identified by MS and MS/MS, with 10
      further confirmed chromatographically by standards. Numerous discriminant
      metabolites were mapped in the steroid hormone biosynthesis pathway. The
      identification of fatty acids, amino acids, lysophospholipids, and bile acids
      provided further insights into the metabolic alterations associated with the
      disease. With additional work, the results presented here show great potential
      toward implementation in clinical settings. 

PMID- 24922592
TI  - A rationally designed fluorescence chemosensor for on-site monitoring of carbon
      monoxide in air.
AB  - A fluorescence chemsensor for carbon monoxide (CO), based on transformation of
      weakly fluorescent iodide to strong fluorescent amino product upon reacting with
      CO, shows abilities of quantitative measurement of CO in air at a level of 50
      1000 ppm and real-time and on-site monitoring for CO flammation/explosion. 

PMID- 24922591
TI  - [Hysterectomies at the Conakry university hospitals: social, demographic, and
      clinical characteristics, types, indications, surgical approaches, and
      prognosis].
AB  - The objectives of this study were to calculate the frequency of hysterectomies at
      the Conakry university hospitals (Donka Hospital and Ignace Deen Hospital),
      describe the women's social, demographic, and clinical characteristics, and
      identify the key indications, the surgical techniques used, and the prognosis.
      This was a 2-year descriptive study, retrospective for the first year (May 2011
      April 2012) and prospective for the second (May 2012-April 2013), of 333
      consecutive hysterectomies performed in the obstetrics and gynecology departments
      of these two hospitals. Hysterectomy is one of the surgical procedures most
      commonly performed in these departments (following cesarean deliveries), with
      frequency of 4.4% interventions. The profile of the women undergoing this surgery
      was that of a woman aged younger than 49 years (61%), married (75.7%),
      multiparous (33%), of childbearing age (61%), and with no history of abdominal or
      pelvic surgery (79.6%). Nearly all hysterectomies were total (95%, compared with
      5% subtotal; the approach was abdominal in 82.25% of procedures and vaginal in
      17.75%. The most common indication for surgery was uterine fibroids (39.6%),
      followed by genital prolapse (22.2%), and obstetric emergencies (17.8%). The
      average duration of surgery was 96 minutes for abdominal and 55 minutes for
      vaginal hysterectomies. The principal intraoperative complication was hemorrhage
      (12.31%), and the main postoperative complication parietal suppuration (21.02%).
      The average length of hospital stay was 10.3 days for abdominal hysterectomies
      and 7.15 days for vaginal procedures. We recorded 14 deaths for a lethality rate
      of 4.2%; most of these deaths were associated with hemorrhagic shock during or
      after an obstetric hysterectomy (93%). Hysterectomy remains a common intervention
      in developing countries. Its indications are common during the pregnancy and
      postpartum period, with high morbidity and mortality rates. Improving obstetric
      coverage could reduce its indications.

PMID- 24922594
TI  - Educating medical students about the personal meaning of terminal illness using
      the film, "Wit".
AB  - BACKGROUND: Addressing the emotional needs of dying patients is rarely found to
      have a place in formal medical curriculum and is also a difficult area to teach
      through classical medical lectures. "Cinemeducation" is a wonderful way to
      educate health care providers about the magnitude of emotions that arise during
      those difficult situations. OBJECTIVE: The aims of this study were to test the
      relevance and usefulness of the movie 'Wit' in teaching medical students about
      the personal meaning of terminal illness and to assess the impact of this
      teaching method on students' attitudes toward palliative care. DESIGN: This was
      an education study using qualitative and quantitative data analysis of 518 first
      year medical students in a single medical faculty in Turkey. Students watched the
      entire film, filled out an evaluation questionnaire, and answered questions about
      the film. Students also expressed their own feelings and thoughts about
      palliative care. RESULTS: Overall, 88% rated the film as excellent, very good, or
      good. According to 54% of the students, the emotions of terminally ill patients
      were fully portrayed in the film and in a very realistic way. Approximately 61.4%
      of the students found this film emotional. Most students (80.5%) stated that this
      film made them think about the emotional and spiritual suffering that dying
      patients go through and found this learning approach about palliative care more
      useful than didactic lectures and journal article readings but not more useful
      than bedside rounds. It was thought that caring for dying patients would be very
      or fairly personally satisfying for 65.3% of the students. CONCLUSIONS: The film
      'Wit' gave the students an opportunity to explore their beliefs, values and
      attitudes in terms of the bio-psycho-social-spiritual aspects of health care and
      encouraged them to think more about the humanitarian issues of the medical
      profession.

PMID- 24922593
TI  - Application of screening experimental designs to assess chromatographic isotope
      effect upon isotope-coded derivatization for quantitative liquid chromatography
      mass spectrometry.
AB  - Isotope effect may cause partial chromatographic separation of labeled (heavy)
      and unlabeled (light) isotopologue pairs. Together with a simultaneous matrix
      effect, this could lead to unacceptable accuracy in quantitative liquid
      chromatography-mass spectrometry assays, especially when electrospray ionization
      is used. Four biologically relevant reactive aldehydes (acrolein,
      malondialdehyde, 4-hydroxy-2-nonenal, and 4-oxo-2-nonenal) were derivatized with
      light or heavy (d3-, (13)C6-, (15)N2-, or (15)N4-labeled) 2,4
      dinitrophenylhydrazine and used as model compounds to evaluate chromatographic
      isotope effects. For comprehensive assessment of retention time differences
      between light/heavy pairs under various gradient reversed-phase liquid
      chromatography conditions, major chromatographic parameters (stationary phase,
      mobile phase pH, temperature, organic solvent, and gradient slope) and different
      isotope labelings were addressed by multiple-factor screening using experimental
      designs that included both asymmetrical (Addelman) and Plackett-Burman schemes
      followed by statistical evaluations. Results confirmed that the most effective
      approach to avoid chromatographic isotope effect is the use of (15)N or (13)C
      labeling instead of deuterium labeling, while chromatographic parameters had no
      general influence. Comparison of the alternate isotope-coded derivatization assay
      (AIDA) using deuterium versus (15)N labeling gave unacceptable differences (>15%)
      upon quantifying some of the model aldehydes from biological matrixes. On the
      basis of our results, we recommend the modification of the AIDA protocol by
      replacing d3-2,4-dinitrophenylhydrazine with (15)N- or (13)C-labeled derivatizing
      reagent to avoid possible unfavorable consequences of chromatographic isotope
      effects. 

PMID- 24922595
TI  - Spelling errors among children with ADHD symptoms: the role of working memory.
AB  - Research has shown that children with attention deficit/hyperactivity disorder
      (ADHD) may present a series of academic difficulties, including spelling errors.
      Given that correct spelling is supported by the phonological component of working
      memory (PWM), the present study examined whether or not the spelling difficulties
      of children with ADHD are emphasized when children's PWM is overloaded. A group
      of 19 children with ADHD symptoms (between 8 and 11 years of age), and a group of
      typically developing children matched for age, schooling, gender, rated
      intellectual abilities, and socioeconomic status, were administered two dictation
      texts: one under typical conditions and one under a pre-load condition that
      required the participants to remember a series of digits while writing. The
      results confirmed that children with ADHD symptoms have spelling difficulties,
      produce a higher percentages of errors compared to the control group children,
      and that these difficulties are enhanced under a higher load of PWM. An analysis
      of errors showed that this holds true, especially for phonological errors. The
      increased errors in the PWM condition was not due to a tradeoff between working
      memory and writing, as children with ADHD also performed more poorly in the PWM
      task. The theoretical and practical implications are discussed. 

PMID- 24922596
TI  - The movement patterns used to rise from a supine position by children with
      developmental delay and age-related differences in these.
AB  - The purposes of this study were to determine (1) movement patterns and strategies
      of children with mild to moderate developmental delay (DD) used to rise up and
      how they differ from those used by age-matched children with typical development
      (TD), (2) whether the movement patterns differ with age in children with DD, and
      (3) to determine the developmental sequences for the UE, AX and LE in children
      with DD and whether they are different from those used by children with TD. Sixty
      six children with TD and 31 children with DD aged two to six years were
      recruited. Peabody Developmental Motor Scale II (PDMS-2) was used to determine
      the motor performance level. The participants were recorded during rising for at
      least five repetitions. Two trained pediatric physical therapists viewed each
      video recording and classified the movement patterns of the upper extremities
      (UE), trunk/axial (AX) and lower extremities (LE) regions using descriptive
      categories developed by previous researchers. The DD and TD groups were further
      divided into four subgroups each using a one-year interval. The percentage of
      occurrence of the each UE, AX and LE movement was determined and compared across
      subgroups, and between each age-matched pair of TD and DD groups. The results
      demonstrated that the participants in the TD group clearly followed the proposed
      developmental sequence and the children with DD followed the developmental
      sequences but with different maturation speeds and greater variability,
      especially at the age of three to five years. The most common movement patterns
      used by the children in each of the DD subgroups were at least one developmental
      categorical pattern behind those used by the age-matched children with TD before
      five years old, except for the LE region. In the DD group, the movement patterns
      had moderate to high correlation with the child's motor performance level,
      indicating that the children with better motor performances used more
      developmentally advanced patterns in comparison with those with lower scores.
      However, besides motor maturity, numerous other intrinsic/extrinsic factors may
      affect the child's performance of this task. The information obtained in this
      study would assist therapists when working with the children with DD, so that
      they can provide individualized treatment rather than guiding all such children
      toward a single, mature pattern. 

PMID- 24922597
TI  - Thermal evaporation and characterization of Sb2Se3 thin film for substrate
      Sb2Se3/CdS solar cells.
AB  - Sb2Se3 is a promising absorber material for photovoltaic cells because of its
      optimum band gap, strong optical absorption, simple phase and composition, and
      earth-abundant and nontoxic constituents. However, this material is rarely
      explored for photovoltaic application. Here we report Sb2Se3 solar cells
      fabricated from thermal evaporation. The rationale to choose thermal evaporation
      for Sb2Se3 film deposition was first discussed, followed by detailed
      characterization of Sb2Se3 film deposited onto FTO with different substrate
      temperatures. We then studied the optical absorption, photosensitivity, and band
      position of Sb2Se3 film, and finally a prototype photovoltaic device
      FTO/Sb2Se3/CdS/ZnO/ZnO:Al/Au was constructed, achieving an encouraging 2.1% solar
      conversion efficiency. 

PMID- 24922598
TI  - CD27(+)CD56Bright natural killer cells may be involved in spontaneous clearance
      of acute hepatitis C in HIV-positive patients.
AB  - OBJECTIVE: The objective of this study was to analyse the potential role of CD27
      in natural killer (NK) cell-mediated control of hepatitis C virus (HCV) infection
      in HIV-positive patients. DESIGN: Frequency of CD27-expressing CD56 NK cells was
      analysed in HIV mono-infected individuals and HIV-positive patients with acute or
      chronic hepatitis C. Anti-HCV activity of CD27(+) and CD27(-) NK cells was
      compared. METHODS: NK cell mediated inhibition of HCV replication was analysed
      using the HUH7 HCV Replicon model. NK cell phenotype and interferon (IFN)
      secretion was studied by flowcytometry. RESULTS: High frequency of CD27(+)CD56 NK
      cells is associated with spontaneous clearance of acute hepatitis C in HIV
      positive patients. Accordingly, we found CD27(+)CD56 NK cells to display strong
      anti-HCV activity. CONCLUSION: Our results underline the important role of NK
      cells in modulating outcome of HCV infection.

PMID- 24922599
TI  - Analysis of interaction property of calycosin-7-O-beta-D-glucoside with human gut
      microbiota.
AB  - Calycosin-7-O-beta-d-glucoside as the major isoflavonoids in Astragali Radix has
      been investigated intensively and has been reported to possess a wide range of
      pharmacological properties. However, the route and metabolites of calycosin-7-O
      beta-d-glucoside by human intestinal bacteria are not well understood and its
      metabolites may accumulate to exert physiological effects. Therefore, the
      objective of this study was to screen the ability of the bacteria to metabolize
      calycosin-7-O-beta-d-glucoside and assess the effect of this compound on the
      intestinal bacteria. Finally, five strains including Bacteroides sp.13, and
      sp.58, Clostridium sp.21-2, Veillonella sp.43-1, and Bacillus sp.46 were isolated
      from human intestinal bacteria and were studied their abilities to convert
      calycosin-7-O-beta-d-glucoside. A total of six metabolites were identified in
      human incubated solution by ultra performance liquid chromatography/quadrupole
      time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The results indicated that
      hydrolysis, demethylation, dehydroxylation and acetylation were the major
      metabolism of calycosin-7-O-beta-d-glucoside. On the other hand, different
      strains of intestinal bacteria have varying degrees of growth sensitivity to
      calycosin-7-O-beta-d-glucoside. Growth of certain pathogenic bacteria such as
      Enterobacter, Enterococcus, Clostridium and Bacteroides was significantly
      repressed by calycosin-7-O-beta-d-glucoside, while commensal probiotics such as
      Lactobacillus, Bifidobacterium were less severely affected. This indicates that
      calycosin-7-O-beta-d-glucoside exert significant effects on the intestinal
      environment by modulation of the intestinal bacterial population. Our observation
      provided further evidence for the importance of intestinal bacteria in the
      metabolism, absorption and potential activity of calycosin-7-O-beta-d-glucoside
      in human health and diseases. 

PMID- 24922600
TI  - Development and validation a liquid chromatography mass spectrometry for
      determination of solasodine in rat plasma and its application to a
      pharmacokinetic study.
AB  - Solasodine is a poisonous alkaloid chemical compound that occurs in plants of the
      Solanaceae family. A simple and selective liquid chromatography mass spectrometry
      method for determination of solasodine in rat plasma was developed and validated
      over the range of 3-1,000 ng/mL. Chromatographic separation was achieved on a C18
      (2.1 mm*50 mm, 3.5 MUm) column with acetonitrile-0.1% formic acid in water as
      mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. After
      addition of midazolam as internal standard (IS), liquid-liquid extraction by
      ethyl acetate was used as sample preparation. An electrospray ionization source
      was applied and operated in positive ion mode; selective ion monitoring mode was
      used for quantification with target ions m/z 414 for solasodine and m/z 326 for
      IS. Mean recoveries of solasodine in rat plasma were in the range of 87.6-94.1%.
      Matrix effects for solasodine were between 94.9% and 102.3%. Coefficient of
      variation of intra-day and inter-day precision were both <13%. The accuracy of
      the method ranged from 94.4% to 105.3%. The method was successfully applied to a
      pharmacokinetic study of solasodine after oral administration of 20mg/kg in rats.

PMID- 24922601
TI  - An amorphous silicon photodiode microfluidic chip to detect nanomolar quantities
      of HIV-1 virion infectivity factor.
AB  - A hydrogenated amorphous silicon (a-Si:H) photosensor was explored for the
      quantitative detection of a HIV-1 virion infectivity factor (Vif) at a detection
      limit in the single nanomolar range. The a-Si:H photosensor was coupled with a
      microfluidic channel that was functionalized with a recombinant single chain
      variable fragment antibody. The biosensor selectively recognizes HIV-1 Vif from
      human cell extracts. 

PMID- 24922602
TI  - Changing face of beta2-adrenergic and muscarinic receptor therapies in asthma.
AB  - Despite current available treatment options, a significant proportion of patients
      with asthma remain uncontrolled and asthma pharmacotherapy continues to evolve.
      beta2-Adrenergic receptor agonists play a major role as bronchodilators in asthma
      therapy, although new perspectives reflect the potential for bias G-protein
      coupled receptor signaling pathways. Due to the success of muscarinic antagonists
      in chronic obstructive pulmonary disease, and the elucidation that muscarinic
      receptors play a role in airway remodeling, muscarinic receptors represent an
      attractive therapeutic target in asthma. Although short-acting muscarinic
      antagonists are currently limited to their use in acute asthma and as alternative
      bronchodilators in individuals who experience side effects with beta2-agonists,
      recent clinical trials indicate that the long-acting muscarinic antagonist,
      tiotropium, deserves consideration as a potential therapeutic agent for select
      populations. The continued evolution of anticholinergic therapy in asthma will
      require appropriately designed studies to assess mechanisms, efficacy and safety
      in asthma. 

PMID- 24922603
TI  - Effect of pelvic suspension on the instrumental meat quality characteristics of
      red deer (Cervus elaphus) and fallow deer (Dama dama) venison.
AB  - The effect of pelvic and Achilles tendon suspension of red and fallow deer
      carcasses on meat quality parameters were compared. Venison was evaluated from
      red deer stags (n=14), bucks (n=14) and fallow deer does (n=10) between 12 and
      36months old. Immediately after slaughter, carcasses were split down the dorsal
      midline and assigned to one of the two hanging methods and pH and core body
      temperature measured. Twenty-four hours post-slaughter muscles were excised.
      Venison from fallow deer and red deer stags pelvic-suspended had significantly
      lower (P<0.001) cooked shear force values than Achilles hung carcasses. There was
      no significant difference between hanging technique for other characteristics
      measured. These data indicated that pelvic suspension should be adopted by the
      deer industry to increase tenderness of venison. 

PMID- 24922604
TI  - Copper-catalyzed radical cyclization to access 3-hydroxypyrroloindoline:
      biomimetic synthesis of protubonine A.
AB  - An unprecedented copper-catalyzed intramolecular radical cyclization was
      developed for the synthesis of 3-hydroxypyrroloindoline skeletons in excellent
      yields. The 3-hydroxyl group was introduced by trapping the radical intermediate
      with molecular oxygen or TEMPO. This process represents a unique radical
      oxidation pathway for tryptamine/tryptophan derivatives and allows a rapid
      biomimetic synthesis of natural product protubonine A. 

PMID- 24922605
TI  - Titanium dioxide nanomaterials for sensor applications.

PMID- 24922606
TI  - Women's land ownership and risk of HIV infection in Kenya.
AB  - Theory predicts that land ownership empowers women to avoid HIV acquisition by
      reducing their reliance on risky survival sex and enhancing their ability to
      negotiate safer sex. However, this prediction has not been tested empirically.
      Using a sample of 5511 women working in the agricultural sector from the 1998,
      2003 and 2008-09 Kenya Demographic and Health Surveys, we examined the
      relationship between women's land ownership and participation in transactional
      sex, multiple sexual partnerships and unprotected sex, and HIV infection status.
      We controlled for demographic characteristics and household wealth, using
      negative binomial and logistic regression models. Women's land ownership was
      associated with fewer sexual partners in the past year (incidence rate ratio,
      0.98; 95% confidence interval [CI], 0.95-1.00) and lower likelihood of engaging
      in transactional sex (odds ratio [OR], 0.67; 95% CI: 0.46-0.99), indicators of
      reduced survival sex, but was not associated with unprotected sex with casual
      partners (OR, 0.64; 95% CI, 0.35-1.18) or with unprotected sex with any partner
      among women with high self-perceived HIV risk (OR, 1.02; 95% CI, 0.57-1.84),
      indicating no difference in safer sex negotiation. Land ownership was also
      associated with reduced HIV infection among women most likely to engage in
      survival sex, i.e., women not under the household headship of a husband (OR,
      0.40; 95% CI, 0.18-0.89), but not among women living in husband-headed
      households, for whom increased negotiation for safer sex would be more relevant
      (OR, 1.74; 95% CI, 0.92-3.29). These findings suggest that reinforcing women's
      land rights may reduce reliance on survival sex and serve as a viable structural
      approach to HIV prevention, particularly for women not in a husband's household,
      including unmarried women and female household heads. 

PMID- 24922607
TI  - Evaluating return on investment in a school based health promotion and prevention
      program: the investment multiplier for the Stephanie Alexander Kitchen Garden
      National Program.
AB  - Successful health promotion and disease prevention strategies in complex
      community settings such as primary schools rely on acceptance and ownership
      across community networks. Assessing multiplier impacts from investment on
      related community activity over time are suggested as key alongside evidence of
      program health effects on targeted groups of individuals in gauging community
      network engagement and ownership, dynamic impacts, and program long term success
      and return on investment. An Australian primary school based health promotion and
      prevention strategy, the Stephanie Alexander Kitchen Garden National Program
      (SAKGNP), which has been providing garden and kitchen classes for year 3-6
      students since 2008, was evaluated between 2011 and 2012. Returns on Australian
      Federal Government investment for school infrastructure grants up to $60,000 are
      assessed up to and beyond a two year mutual obligation period with: (i) Impacts
      on student lifestyle behaviours, food choices and eating habits surveyed across
      students (n = 491 versus 260) and parents (n = 300 versus 234) in 28 SAKGNP and
      14 matched schools, controlling for school and parent level confounders and
      triangulated with SAKGNP pre-post analysis; (ii) Multiplier impacts of investment
      on related school and wider community activity up to two years; and (iii)
      Evidence of continuation and program evolution in schools observed beyond two
      years. SAKGNP schools showed improved student food choices (p = 0.024) and
      kitchen lifestyle behaviour (p = 0.019) domains compared to controls and in pre
      post analysis where 20.0% (58/290) reported eating fruit and vegetables more
      often and 18.6% (54/290) preparing food at home more often. No significant
      differences were found in case control analysis for eating habits or garden
      lifestyle behaviour domains, although 32.3% of children helped more in the garden
      (91/278) and 15.6% (45/289) ate meals together more often in pre-post analysis.
      The multiplier impact on total community activity up to two years was 5.07
      ($226,737/$44,758); 1.60 attributable to school, and 2.47 to wider community,
      activity. All 8 schools observed beyond two years continued garden and kitchen
      classes, with an average 17% scaling up and one school fully integrating staff
      into the curriculum. In conclusion evidence supports the SAKGNP to be a
      successful health promotion program with high community network impacts and
      return on investment in practice. 

PMID- 24922608
TI  - Uneasy subjects: medical students' conflicts over the pharmaceutical industry.
AB  - In this article I report on an investigation of the pharmaceutical industry's
      influence in medical education. Findings are based on fifty semi-structured
      interviews with medical students in the United States and Canada conducted
      between 2010 and 2013. Participant responses support the survey-based literature
      demonstrating that there is clear and pervasive influence of the pharmaceutical
      industry in medical education. They also challenge the theory that medical
      students feel entitled to industry gifts and uncritically accept industry
      presence. I investigate how medical students who are critical of the
      pharmaceutical industry negotiate its presence in the course of their medical
      education. Findings suggest that these participants do not simply absorb industry
      presence, but interpret it and respond in complex ways. Participants were
      uncomfortable with industry influence throughout their medical training and found
      multifaceted ways to resist. They struggled with power relations in medical
      training and the prevailing notion that industry presence is a normal part of
      medical education. I argue that this pervasive norm of industry presence is
      located in neoliberal structural transformations within and outside both
      education and medicine. The idea that industry presence is normal and inevitable
      represents a challenge for students who are critical of industry. 

PMID- 24922609
TI  - Understanding resilience in armed conflict: social resources and mental health of
      children in Burundi.
AB  - Little is known about the role of cognitive social capital among war-affected
      youth in low- and middle-income countries. We examined the longitudinal
      association between cognitive social capital and mental health (depression and
      posttraumatic stress disorder (PTSD) symptoms), functioning, and received social
      support of children in Burundi. Data were obtained from face-to-face interviews
      with 176 children over three measurement occasions over the span of 4-months.
      Cognitive social capital measured the degree to which children believed their
      community was trustworthy and cohesive. Mental health measures included the
      Depression Self-Rating Scale (DSRS) (Birleson, 1981), the Child Posttraumatic
      Symptom Scale (Foa et al., 2001), and a locally constructed scale of functional
      impairment. Children reported received social support by listing whether they
      received different types of social support from self-selected key individuals.
      Cross-lagged path analytic modeling evaluated relationships between cognitive
      social capital, symptoms and received support separately over baseline (T1), 6
      week follow-up (T2), and 4-month follow-up (T3). Each concept was treated and
      analyzed as a continuous score using manifest indicators. Significant
      associations between study variables were unidirectional. Cognitive social
      capital was associated with decreased depression between T1 and T2 (B = -.22, p <
      .001) and T2 and T3 (beta = -.25, p < .001), and with functional impairment
      between T1 and T2 (beta = -.15, p = .005) and T2 and T3 (beta = -.14, p = .005);
      no association was found for PTSD symptoms at either time point. Cognitive social
      capital was associated with increased social support between T1 and T2 (beta =
      .16, p = .002) and T2 and T3 (beta = .16, p = .002). In this longitudinal study,
      cognitive social capital was related to a declining trajectory of children's
      mental health problems and increases in social support. Interventions that
      improve community relations in war-affected communities may alter the
      trajectories of resource loss and gain with conflict-affected children. 

PMID- 24922610
TI  - Quality of life in children with narcolepsy.
AB  - AIMS: To evaluate the health-related quality of life (HRQL) and its correlates in
      children and adolescents with narcolepsy. METHODS: We compared the clinical
      characteristics of control subjects and patients with primary narcolepsy from
      data collected at the National Reference Centers for Narcolepsy. RESULTS: The
      cohort included 69 control subjects (29 boys) and 117 patients (65 boys; 59 de
      novo patients). Cataplexy was present in 81% and DQB1*0602 was positive in 91%.
      The control children were older (13.5+/-3.2 vs. 11.6+/-3.1 years, P<0.001) and
      less obese (1.4% vs. 60%, P<0.001). Twenty-five percent of the patients and 15.6%
      of the control subjects had clinically significant depressive feelings on
      Children's Depression Inventory (CDI>=16) (NS). Fifty-three narcoleptic and 43
      control adolescents, 31 narcoleptic children and 23 control children filled out
      the HRQL questionnaires as well as 83 parents of patients and 60 parents of
      control subjects. Narcolepsy seriously impacts HRQL in terms of vitality,
      physical well-being, relations with friends and leisure activities, especially in
      adolescents. Depression was the factor that most affected HRQL in both
      narcoleptic and control subjects. For the control subjects and the narcoleptic
      patients, when the CDI score was entered into the multivariable regression model
      adjusted for gender and age, no other continuous independent variable could
      significantly increase the likelihood of the model. When the CDI score increased
      by 1, the mean HRQL score decreased by 1.7 for narcoleptic patients and 1.5 for
      control subjects. Apnea-hypopnoea index, diagnosis delay, disease duration,
      obesity, the presence of cataplexy or treatment had no effects on HRQL.
      CONCLUSIONS: Narcoleptic children and adolescents were at high risk for poor
      HRQL. Depressive symptoms had a major impact on HRQL. We recommend a more
      thorough assessment and management of psychological health in this population.

PMID- 24922611
TI  - Tracing fecal pollution sources in karst groundwater by Bacteroidales genetic
      biomarkers, bacterial indicators, and environmental variables.
AB  - Fecal contamination in Midwestern karst regions was evaluated by simultaneously
      measuring traditional bacterial indicators (coliforms and Escherichia coli),
      Bacteroidales-based biomarkers, and environmental variables. Water samples from
      springs and wells were collected from karst regions in Illinois (IL), Wisconsin
      (WI), Kentucky (KY), and Missouri (MO). Quantitative PCR (Q-PCR) with seven
      primer sets targeting different members of Bacteroidales was used to determine
      the origin of fecal contamination (i.e., from human waste, livestock waste, or
      both). Most samples were contaminated by both human and animal waste, with a few
      samples showing pollution solely by one or the other. Spring water tended to have
      higher levels of contamination than well water, and higher concentrations of
      fecal biomarkers were detected in urban springs compared to rural spring systems.
      However, there were discrepancies on contamination profile determined by
      Bacteroidales-based biomarkers and by traditional bacterial indicators. Among all
      the environmental parameters examined, E. coli, sulfate, total dissolved solids
      (TDS), and silicon were significantly correlated (p<0.05) with the level of
      Bacteroidales-based fecal indicators. A rapid screening method using total
      nitrogen (TN) and chloride (Cl(-)) concentrations to determine fecal
      contamination was shown to be effective and correlated well with Bacteroidales
      based MST. The results suggest that human and livestock feces co-contaminated a
      large portion of karst groundwater systems in Midwestern regions, and the
      inclusion of traditional bacterial indicators, environmental variables, and
      Bacteroidales-based MST is an effective approach for identifying fecal
      contamination in karst regions. 

PMID- 24922612
TI  - A preliminary study of sexual activity as a distraction for young drivers.
AB  - In what may be the first in-depth study of sexual activity as a driving
      distraction in the US, a sample of 195 male and 511 female college students at a
      Midwestern university (M age=19.7) participated in an on-line study of sex while
      driving (SWD). Of these, 64 (32.8%) men and 47 (9.3%) women had engaged in sex
      while driving (SWD). Nine percent of men and 29% of women had engaged in SWD as a
      passenger. In most recent SWD incidents, respondents reported that the two most
      common acts were oral sex (70.3%) and genital touching (60.4%). About 11% engaged
      in vaginal intercourse. Sexual activity lasted from 1 to 10min for 42.7% of the
      respondents. Nearly half (49.1%) were traveling 61-80mph during sex. Considering
      respondents' lifetime incidents of SWD, the most common driving errors reported
      were speeding (37.8%), drifting into another lane (36%), and letting go of the
      steering wheel (10.8%). Only 1.8% nearly had a crash, and none actually had a
      crash. Separate regression analyses for male and female respondents revealed that
      lower intentions to engage in SWD in the future were associated with higher
      estimates of the probability of a car crash. The authors consider SWD to be an
      under-reported in-vehicle distraction and encourage more research and prevention
      efforts. 

PMID- 24922613
TI  - Attentional bias toward safety predicts safety behaviors.
AB  - Safety studies have primarily focused on how explicit processes and measures
      affect safety behavior and subsequent accidents and injuries. Recently, safety
      researchers have paid greater attention to the role of implicit processes. Our
      research focuses on the role of attentional bias toward safety (ABS) in workplace
      safety. ABS is a basic, early-stage cognitive process involving the automatic and
      selective allocation of attentional resources toward safety cues, which reflect
      the implicit motivational state of employees regarding safety goal. In this
      study, we used two reaction time-based paradigms to measure the ABS of employees
      in three studies: two modified Stroop tasks (Studies 1 and 2) and a visual dot
      probe task (Study 3). Results revealed that employees with better safety behavior
      showed significant ABS (Study 2), and greater ABS than employees with poorer
      safety behavior (Studies 1 and 2). Moreover, ABS was positively associated with
      the perceived safety climate and safety motivation of employees, both of which
      mediate the effect of ABS on safety behavior (Study 3). These results contributed
      to a deeper understanding of how early-stage automatic perceptual processing
      affects safety behavior. The practical implications of these results were also
      discussed. 

PMID- 24922614
TI  - How effective is drug testing as a workplace safety strategy? A systematic review
      of the evidence.
AB  - The growing prevalence of workplace drug testing and the narrow scope of previous
      reviews of the evidence base necessitate a comprehensive review of research
      concerning the efficacy of drug testing as a workplace strategy. A systematic
      qualitative review of relevant research published between January 1990 and
      January 2013 was undertaken. Inclusion criteria were studies that evaluated the
      effectiveness of drug testing in deterring employee drug use or reducing
      workplace accident or injury rates. Methodological adequacy was assessed using a
      published assessment tool specifically designed to assess the quality of
      intervention studies. A total of 23 studies were reviewed and assessed, six of
      which reported on the effectiveness of testing in reducing employee drug use and
      17 which reported on occupational accident or injury rates. No studies involved
      randomised control trials. Only one study was assessed as demonstrating strong
      methodological rigour. That study found random alcohol testing reduced fatal
      accidents in the transport industry. The majority of studies reviewed contained
      methodological weaknesses including; inappropriate study design, limited sample
      representativeness, the use of ecological data to evaluate individual behaviour
      change and failure to adequately control for potentially confounding variables.
      This latter finding is consistent with previous reviews and indicates the
      evidence base for the effectiveness of testing in improving workplace safety is
      at best tenuous. Better dissemination of the current evidence in relation to
      workplace drug testing is required to support evidence-informed policy and
      practice. There is also a pressing need for more methodologically rigorous
      research to evaluate the efficacy and utility of drug testing. 

PMID- 24922615
TI  - Diterpenes from the endangered goldenrod Solidago shortii.
AB  - Species extinction is tantamount to loss of chemical diversity, and so it is
      important to seize all opportunities to study species on the brink of extinction.
      Such studies are often hampered by the limited material available, but that
      obstacle is surmountable through collaboration with botanical gardens and
      advances in instrumentation. The goldenrod Solidago shortii is one example of an
      endangered species native to the United States. From S. shortii, one known
      diterpene (1), two new diterpenes (2 and 3), and three new hydrolysis products (4
      6) are described. This work was made possible through collaboration with the
      Missouri Botanical Garden and with the use of highly sensitive microcryoprobe NMR
      technology for structure elucidation and VCD spectroscopy for the determination
      of absolute configuration. 

PMID- 24922616
TI  - [Hepatitis B virus serologic status among hospital health care staff in Lome].
AB  - To assess the hepatitis B virus (HBV) serologic status of hospital health care
      personnel in Lome. From June 1 to August 31, 2007, 100 workers vaccinated against
      HBV and 50 unvaccinated workers participated in this comparative cross-sectional
      study. The data studied were: age, sex, vaccination status, history of accidental
      exposure to blood, and enzyme-linked immunoassay results for HBs antigen (Ag),
      total anti-HBc antibodies (Ab), and anti-HBs Ab. Vaccinated subjects had a mean
      age of 33.2 +/- 8.2 years and unvaccinated subjects of 35.2 +/- 9.6 years; their
      respective sex ratios (M:W) were 2:1 and 3:1. Protective levels (>10 IU/L) of
      anti-HBs Ab were found in 78% (n = 78) of vaccinated subjects compared with 44%
      (n = 22) of those unvaccinated. HBs Ag was found in 36% (n = 36) of vaccinated
      and 56% (n = 28) of unvaccinated subjects. Of subjects previously accidentally
      exposed to blood, 67% (n = 35) had HBs Ag compared with 30% (n = 29) of those
      subjects without such exposure. This study has proved the high prevalence of HBs
      Ag carrier status among health care workers in Lome and confirms the importance
      of vaccination against HBV. 

PMID- 24922617
TI  - Factors influencing response to intravenous lacosamide in emergency situations:
      LACO-IV study.
AB  - Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in
      emergency visits. Wide variations in response are seen with standard
      antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide
      are approved as adjunctive therapy in the treatment of partial-onset seizures in
      adults and adolescents. The aim of the retrospective multicenter observational
      study (LACO-IV) was to analyze data from a large cohort of patients with SE or
      ARSs of varying severity and etiology, who received IV lacosamide in the
      emergency setting. Patient clinical data were entered into a database; lacosamide
      use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide
      tended to be used mainly in nonconvulsive status epilepticus as second- or third
      line treatment. The proportion of patients with no seizures when IV lacosamide
      was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of
      seizure cessation <= 24 h after IV lacosamide administration was 57.1% (49.1% SE
      and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to
      IV lacosamide infusion influenced treatment response significantly. A
      nonsignificant tendency towards a higher response was seen with lacosamide dose
      >200mg versus <= 200 mg. Analysis of response according to mechanism of action
      showed no significant differences in response to IV lacosamide in patients
      receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE
      population; however, in ARSs, a tendency towards a higher response was observed
      in those receiving non-SCB AEDs. The frequency and nature of adverse events
      observed were in line with those reported in other studies (somnolence being the
      most frequent). In the absence of randomized prospective controlled studies of IV
      lacosamide, our observations suggest that IV lacosamide may be a potential
      alternative for treatment of SE/ARSs when seizures fail to improve with standard
      AEDs or when AEDs are contraindicated or not recommended.

PMID- 24922619
TI  - Gastrocnemius and soleus are selectively activated when adding knee extensor
      activity to plantar flexion.
AB  - The gastrocnemius is a biarticular muscle that acts not only as a plantar flexor,
      but also as a knee flexor, meaning that it is an antagonist during knee
      extension. In contrast, the soleus is a monoarticular plantar flexor. Based on
      this anatomical difference, these muscles' activities should be selectively
      activated during simultaneous plantar flexion and knee extension, which occur
      during many activities of daily living. This study examined the selective
      activation of gastrocnemius and soleus activities when voluntary isometric
      activation of knee extensors was added to voluntary isometric plantar flexion.
      Ten male volunteers performed isometric plantar flexion at 10%, 20%, and 30% of
      maximum effort. During each plantar flexion task, isometric knee extension was
      added at 0%, 50%, and 100% of maximum effort. When knee extension was added, the
      average rectified value of the electromyographic activity of the medial
      gastrocnemius was significantly depressed (P=.002), whereas that of the soleus
      was significantly increased (P<.001) regardless of the plantar flexion level.
      These results suggest that plantar flexion with concurrent knee extensor activity
      leads to selective activation of the soleus and depression of the synergistic
      activity of the gastrocnemius. 

PMID- 24922618
TI  - [Blood exposure accidents: Knowledge, attitudes and practices of nursing and
      midwifery students at the Bobo-Dioulasso teaching hospital (Burkina Faso)].
AB  - Blood exposure accidents are the source of major risks of contamination of
      healthcare personnel. The objective of this study was to describe the knowledge
      of standard precautions, and the attitudes and practices of nursing and midwifery
      students in relation to this accidental exposure. This cross-sectional survey,
      conducted in November 2011, was based on voluntary anonymous questionnaires
      completed by students working in the medical ward of the Bobo-Dioulasso teaching
      hospital. Of the 275 students asked to participate, 219 (92.8%) completed the
      questionnaire: 138 (63,0%) were student nurses and 81 (37.0%) student midwives.
      Their mean age was 27.9 +/- 5 years. Among them, 64 (29.1%) acknowledged
      accidental exposure to blood during treatment performed as part of their hospital
      work. Only 30 of these 64 cases were reported at the time. The standard
      precautions for the prevention of these accidents were known to 131 students
      (59.8%); 58.4% always wore gloves for invasive procedures; 74.9% reported that
      the syringe container was "always" or "often" used. The needles used were
      "always" or "often" recapped before disposal in only 39.1% of cases. Only 11.0%
      were fully vaccinated against hepatitis B. Blood exposure accidents were not
      uncommon among these students and their knowledge of the standard precautions and
      actions to take in case of an accident is insufficient. These data show the need
      for further training and awareness campaigns to improve these hospital practices.

PMID- 24922620
TI  - Integrated experimental and theoretical approach for corrosion and wear
      evaluation of laser surface nitrided, Ti-6Al-4V biomaterial in physiological
      solution.
AB  - A laser based surface nitriding process was adopted to further enhance the osseo
      integration, corrosion resistance, and tribological properties of the commonly
      used bioimplant alloy, Ti-6Al-4V. Earlier preliminary osteoblast,
      electrochemical, and corrosive wear studies of laser nitrided titanium in
      simulated body fluid clearly revealed improvement of cell adhesion as well as
      enhancement in corrosion and wear resistance but mostly lacked the in-depth
      fundamental understanding behind these improvements. Therefore, a novel
      integrated experimental and theoretical approach were implemented to understand
      the physical phenomena behind the improvements and establish the property
      structure-processing correlation of nitrided surface. The first principle and
      thermodynamic calculations were employed to understand the thermodynamic,
      electronic, and elastic properties of TiN for enthalpy of formation, Gibbs free
      energy, density of states, and elastic properties of TiN were investigated.
      Additionally, open circuit potential and cyclic potentio-dynamic polarization
      tests were carried out in simulated body fluid to evaluate the corrosion
      resistance that in turn linked with the experimentally measured and
      computationally predicted surface energies of TiN. From these results, it is
      concluded that the enhancement in the corrosion resistance after laser nitriding
      is mainly attributed to the presence of covalent bonding via hybridization among
      Ti (p) and N (d) orbitals. Furthermore, mechanical properties, such as, Poisson's
      ratio, stiffness, Pugh's ductility criteria, and Vicker's hardness, predicted
      from first principle calculations were also correlated to the increase in wear
      resistance of TiN. All the above factors together seem to have contributed to
      significant improvement in both wear and corrosion performance of nitride surface
      compared to the bare Ti-6Al-4V in physiological environment indicating its
      suitability for bioimplant applications. 

PMID- 24922621
TI  - The impact of long term freezing on the mechanical properties of porcine aortic
      tissue.
AB  - BACKGROUND: Preservation of the native artery's functionality can be important in
      both clinical and experimental applications. Although, simple cryopreservation
      techniques offer an attractive solution to this problem, the extent to which
      freezing affects the tissue's properties is widely debated. Earlier assessments
      of the mechanical properties post-freezing have been limited by one or more of
      the following: small sample numbers, uncontrolled inter-specimen/animal
      variability, failure to account for the impact of potential errors in thickness
      measurements, short storage times and uniaxial test methods. MATERIAL AND
      METHODS: Biaxial mechanical tests were performed on porcine aortic samples (n=89)
      extracted from superior, middle and inferior regions of five aortas, stored in
      isotonic saline at -20 degrees C for 1 day, 1 week, 1, 6 and 12 months, thawed
      and retested. The sample's weight and thickness were also measured pre and post
      freezing. A total of 178 tests were performed and elastic modulus was assessed by
      calculating the slope of the Cauchy stress-stretch curve at the low and high
      stretch regions in both the circumferential (theta) and longitudinal (L)
      directions. RESULTS: The weight of the samples increased post-freezing. However,
      in general, no significant difference was found between the elastic modulus of
      porcine aortic tissue before and after freezing at -20 degrees C and was
      unaffected by storage time. Although more accurate measuring instruments are
      warranted to confirm this finding, minor changes to the elastic modulus as a
      result of freezing were negatively correlated with regional variances i.e.
      changes in the elastic modulus decreased from the superior to the inferior
      region. CONCLUSIONS: These results indicate that for applications which require
      preservation of the gross mechanical properties, storing the tissue at -20
      degrees C in isotonic saline, for an extended period of time, is acceptable.

PMID- 24922622
TI  - The neural bases of argument structure processing revealed by primed lexical
      decision.
AB  - Previous studies have reported anticipatory effects during sentence processing.
      However, the source of these effects has not been clearly characterized. This
      study investigated the hypothesis that one source of anticipatory effects,
      particularly during verb processing, is the automatic triggering of argument
      structure processes. If argument structure processes are automatically triggered
      it was hypothesized that the task need not require the initiation of the process,
      as such a primed lexical decision task was used that examined the neural priming
      of cross-grammatical class prime pairs (e.g., verb-noun priming). While previous
      studies, as does the current study, have revealed behavioral priming for cross
      grammatical class and within-class (noun-noun and verb-verb) prime/target pairs,
      the current results revealed significant activation differences. Enhancement
      effects were observed for cross-grammatical class priming in the language
      network, particularly the inferior frontal gyrus (BA 47), and the posterior
      temporal cortex. Both regions have been linked to argument structure processing
      previously. Within-class priming resulted in neural suppression of the inferior
      temporal/occipital regions. Together, the data presented suggest the automatic
      triggering of argument structure representations and demonstrate that priming is
      a fruitful mechanism to explore aspects of sentence processing. 

PMID- 24922623
TI  - Activation of syntax in lexical production in healthy speakers and in aphasia.
AB  - Theories of spoken word production agree that semantic and phonological
      representations are activated in spoken word production. There is less agreement
      concerning the role of syntax. In this study we investigated noun syntax
      activation in English bare noun naming, using mass and count nouns. Fourteen
      healthy controls and 13 speakers with aphasia took part. Participants named mass
      and count nouns, and completed a related noun syntax judgement task. We analysed
      speakers' noun syntax knowledge when naming accurately, and when making errors in
      production. Healthy speakers' noun syntax judgement was accurate for words they
      named correctly, but this did not correlate with naming accuracy. Speakers with
      aphasia varied in their noun syntax judgement, and this also did not correlate
      with naming accuracy. Healthy speakers' syntax for semantic errors was less
      accurate, as was that for speakers with aphasia. For phonological errors half the
      participants with aphasia could access syntax, half could not, indicating two
      types of phonological error. Individual differences were found in no responses.
      Finally, we found no effect of frequency for any of the above. The lack of a
      relationship between syntax and naming accuracy suggests that syntax is
      available, but access is not obligatory. This finding supports theories
      incorporating non-obligatory syntactic processing, which is independent of
      phonological access. The semantic error data are best explained within such a
      theory where there is damage to phonological access and hence to independent
      syntax. For the aphasia group we identify two types of phonological error, one
      implicating syntax and phonology, and one implicating phonology only, again
      supporting independent access to these systems. Overall the data support a model
      within which syntax is independent of phonology, and activation of syntax
      operates flexibly dependent on task demands and integrity of other processing
      routines. 

PMID- 24922626
TI  - B-type natriuretic peptide predicts 30-day readmission for heart failure but not
      readmission for other causes.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is a marker for heart failure (HF)
      severity, but its association with hospital readmission is not well defined.
      METHODS AND RESULTS: We identified all hospital discharges (n=109 875) with a
      primary diagnosis of HF in the Veterans Affairs Health Care System from 2006 to
      2009. We examined the association between admission (n=53 585), discharge (n=24
      326), and change in BNP (n=7187) and 30-day readmission for HF or other causes.
      Thirty-day HF readmission was associated with elevated admission BNP, elevated
      discharge BNP, and smaller percent change in BNP from admission to discharge.
      Patients with a discharge BNP >= 1000 ng/L had an unadjusted 30-day HF
      readmission rate over 3 times as high as patients whose discharge BNP was <= 200
      ng/L (15% vs. 4.1%). BNP improved discrimination and risk classification for 30
      day HF readmission when added to a base clinical model, with discharge BNP having
      the greatest effect (C-statistic, 0.639 to 0.664 [P<0.0001]; net reclassification
      improvement, 9% [P<0.0001]). In contrast, 30-day readmission for non-HF causes
      was not associated with BNP levels during index HF hospitalization. CONCLUSIONS:
      In this study of over 50 000 veterans hospitalized with a primary diagnosis of
      HF, BNP levels measured during hospitalization were associated with 30-day HF
      readmission, but not readmissions for other causes. These data may help guide
      future study aimed at identifying the optimal timing for hospital discharge and
      help allocate high-intensity, HF-specific transitional care interventions to the
      patients most likely to benefit.

PMID- 24922625
TI  - Cardiac CD47 drives left ventricular heart failure through Ca2+-CaMKII-regulated
      induction of HDAC3.
AB  - BACKGROUND: Left ventricular heart failure (LVHF) remains progressive and fatal
      and is a formidable health problem because ever-larger numbers of people are
      diagnosed with this disease. Therapeutics, while relieving symptoms and extending
      life in some cases, cannot resolve this process and transplant remains the option
      of last resort for many. Our team has described a widely expressed cell surface
      receptor (CD47) that is activated by its high-affinity secreted ligand,
      thrombospondin 1 (TSP1), in acute injury and chronic disease; however, a role for
      activated CD47 in LVHF has not previously been proposed. METHODS AND RESULTS: In
      experimental LVHF TSP1-CD47 signaling is increased concurrent with up-regulation
      of cardiac histone deacetylase 3 (HDAC3). Mice mutated to lack CD47 displayed
      protection from transverse aortic constriction (TAC)-driven LVHF with enhanced
      cardiac function, decreased cellular hypertrophy and fibrosis, decreased
      maladaptive autophagy, and decreased expression of HDAC3. In cell culture,
      treatment of cardiac myocyte CD47 with a TSP1-derived peptide, which binds and
      activates CD47, increased HDAC3 expression and myocyte hypertrophy in a
      Ca(2+)/calmodulin protein kinase II (CaMKII)-dependent manner. Conversely,
      antibody blocking of CD47 activation, or pharmacologic inhibition of CaMKII,
      suppressed HDAC3 expression, decreased myocyte hypertrophy, and mitigated
      established LVHF. Downstream gene suppression of HDAC3 mimicked the protective
      effects of CD47 blockade and decreased hypertrophy in myocytes and mitigated LVHF
      in animals. CONCLUSIONS: These data identify a proximate role for the TSP1-CD47
      axis in promoting LVHF by CaKMII-mediated up-regulation of HDAC3 and suggest
      novel therapeutic opportunities.

PMID- 24922627
TI  - Hospital variation in survival trends for in-hospital cardiac arrest.
AB  - BACKGROUND: During the past decade, survival after in-hospital cardiac arrest has
      improved markedly. It remains unknown whether the improvement in survival has
      occurred uniformly at all hospitals or was driven by large improvements at only a
      few hospitals. METHODS AND RESULTS: We identified 93 342 adults with an in
      hospital cardiac arrest at 231 hospitals in the Get With The Guidelines((r))
      Resuscitation registry during 2000-2010. Using hierarchical regression models, we
      evaluated hospital-level trends in survival to discharge. Mean age was 66 years,
      59% were men, and 21% were black. Between 2000 and 2010, there was a significant
      decrease in age, prevalence of heart failure and myocardial infarction, and
      cardiac arrests due to shockable rhythms (P<0.001 for all) and an increase in
      prevalence of sepsis, respiratory insufficiency, renal insufficiency, intensive
      care unit location, and mechanical ventilation before arrest (P<0.001 for all).
      After adjustment for temporal trends in baseline characteristics, hospital rates
      of in-hospital cardiac arrest survival improved by 7% per year (odds ratio [OR]
      1.07, 95% CI 1.06 to 1.08, P<0.001). Improvement in survival varied markedly and
      ranged from 3% in the bottom hospital quartile to 11% in the top hospital
      quartile. Compared with minor teaching hospitals (OR 1.04, 95% CI 1.02 to 1.06),
      hospital rate of survival improvement was greater at major teaching (OR 1.08, 95%
      CI 1.06 to 1.10) and nonteaching hospitals (OR 1.07, 95% CI 1.05 to 1.09, P value
      for interaction=0.03). CONCLUSION: Although in-hospital cardiac arrest survival
      has improved during the past decade, the magnitude of improvement varied across
      hospitals. Future studies are needed to identify hospital processes that have led
      to the largest improvement in survival.

PMID- 24922629
TI  - Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of
      prostate cancer.
AB  - Prophylactic vaccination is arguably the most effective medical preventative
      method. After local inoculation, vaccines induce antigen-specific systemic
      immunity, protecting the whole body. Systemic antitumour immunity can cure
      advanced cancer, but will therapeutic vaccination suffice? A vaccine for
      castration-refractory prostate cancer (CRPC) was approved by regulatory
      authority, but its evidence is disputed. We critically reviewed the clinical
      efficacy of therapeutic cancer vaccines for prostate cancer, including the
      results of 31 clinical studies employing vaccines-only, and another 10 studies
      combining vaccines with immune co-stimulation. Vaccinations yielded immunological
      responses, but no study showed evidence for clinically relevant therapeutic
      improvement. Clinical failure of therapeutic vaccination is discussed in the
      light of immunological dogmas and mechanisms of antitumour therapies. We propose
      that cancer immunotherapy might be improved by immunological danger, i.e.
      disturbing tumour homeostasis by destroying the tumour tissue or inducing local
      inflammation. Such danger might override immunological tolerance, and thereby
      allow clinically relevant anticancer results. 

PMID- 24922628
TI  - Fibroblast growth factor-23 and incident coronary heart disease, heart failure,
      and cardiovascular mortality: the Atherosclerosis Risk in Communities study.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone involved in
      phosphorous regulation and vitamin D metabolism that may be associated with
      cardiovascular risk, and it is a potential target for intervention. We tested
      whether elevated FGF-23 is associated with incident coronary heart disease, heart
      failure, and cardiovascular mortality, even at normal kidney function. METHODS
      AND RESULTS: A total of 11 638 Atherosclerosis Risk In Communities study
      participants, median age 57 at baseline (1990-1992), were followed through 2010.
      Cox regression was used to evaluate the independent association of baseline serum
      active FGF-23 with incident outcomes. Models were adjusted for traditional
      cardiovascular risk factors and estimated glomerular filtration rate. During a
      median follow-up of 18.6 years, 1125 participants developed coronary heart
      disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For
      all 3 outcomes, there was a threshold, whereby FGF-23 was not associated with
      risk at <40 pg/mL but was positively associated with risk at >40 pg/mL. Compared
      with those with FGF-23 <40 pg/mL, those in the highest FGF-23 category (>= 58.8
      pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard
      ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and
      cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly
      attenuated but remained statistically significant after further adjustment for
      estimated glomerular filtration rate. In stratified analyses, similar results
      were observed in African Americans and among persons with normal kidney function.
      CONCLUSIONS: High levels of serum FGF-23 were associated with increased risk of
      coronary heart disease, heart failure, and cardiovascular mortality in this
      large, biracial, population-based cohort. This association was independent of
      traditional cardiovascular risk factors and kidney function.

PMID- 24922630
TI  - Vascularized bone graft for oncological reconstruction of the extremities: review
      of the biological advantages.
AB  - Vascularized bone graft (VBG) is a form of vascularized bone marrow transplant in
      which the bone marrow is surgically grafted with its microenvironment intact. Due
      to the preservation of cellular viability, VBG have significant advantages over
      non-vascularized bone grafts. Free vascularized fibula grafts have superior
      material properties and tolerate infection. Bone healing can be accomplished in a
      shorter period, even in an irradiated bed. In addition to these properties, VBG
      has other biological advantages that are not always familiar to oncological
      surgeons. Hypertrophic change can be divided into reactive and adaptive
      hypertrophy. Early hypertrophy is associated with donor-derived cells, whereas
      later remodeling is associated with recipient-derived cells. VBG has significant
      advantages in enhancing neo-revascularization of necrotic bone. We reviewed VBG
      from a novel viewpoint that stems from our basic research. 

PMID- 24922631
TI  - MicroRNAs in testicular cancer: implications for pathogenesis, diagnosis,
      prognosis and therapy.
AB  - Testicular germ cell tumors (TGCTs) represent the most common type of solid
      tumors among men aged 15 to 40 years. An increasing incidence has been recorded
      in developed countries. In clinical practice, TGCTs are classified as seminomas
      and non-seminomatous tumors. Non-seminomatous tumors often contain multiple
      different cell types and can be further sub-divided according to the histological
      and cellular phenotype in embryonal carcinomas, choriocarcinomas, yolk sac tumors
      and teratomas. For the clinical management of TGCTs, blood-based markers such as
      lactate dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin are
      essential tools for diagnosis, risk assessment and patient's prognosis. However,
      only 60% of patients with TGCTs show increased serum levels of these tumor
      markers. This proportion of patients is even lower for those with seminomas or
      pure embryonal carcinomas as alpha-fetoprotein is predominantly related to yolk
      sac tumor and human chorionic gonadotropin to choriocarcinoma. 

PMID- 24922632
TI  - Oxazine derivatives of gamma- and delta-tocotrienol display enhanced anticancer
      activity in vivo.
AB  - BACKGROUND: Oxazine derivatives of tocotrienols display enhanced anticancer
      activity. Studies were conducted to further characterize these effects in vivo.
      MATERIALS AND METHODS: Tetrazolium assay was used to determine the inhibitory
      effects of oxazine derivatives of gamma-tocotrienol and delta-tocotrienol in
      vitro. These compounds were further formulated as lipid nanoemulsions and
      intralesional administration was used to examine their anticancer activity in
      vivo. RESULTS: Tocotrienol oxazine derivatives significantly inhibited +SA
      mammary tumor growth in syngeneic mice as compared to their respective parent
      compound, and these effects were associated with a reduction in cell
      proliferation and survival (phosphorylated protein kinase B (AKT) and nuclear
      factor kappa-light-chain-enhancer of activated B cells (NFkappaB), and
      cyclooxygenase-2 (COX2) and cell-cycle progression (cyclin D1, cyclin-dependent
      kinase 2 (CDK2), CDK4 and CDK6) markers, and increase in cell-cycle arrest
      proteins (p21 and p27). CONCLUSION: Tocotrienol oxazine derivatives may provide
      benefit as therapeutic agents against breast cancer.

PMID- 24922633
TI  - Immunohistochemical evidence of association between ghrelin expression and tumor
      growth in esophageal carcinoma.
AB  - BACKGROUND: Ghrelin, an orexigenic peptide, is primarily produced and secreted by
      the gastrointestinal tract. As far as we are aware of, there is no evidence of
      ghrelin expression in esophageal squamous cell carcinoma (ESCC). MATERIALS AND
      METHODS: Two hundred and ten patients with ESCC who underwent surgical resection
      were enrolled in this study. We immunohistochemically investigated ghrelin
      expression in primary ESCC specimens and analyzed the relationship with
      clinicopathological factors. RESULTS: High ghrelin expression was observed in 61
      patients (29.0%). Depth of tumor invasion and histological differentiation were
      statistically associated with ghrelin expression. As for depth of tumor invasion,
      the deeper it was, the higher was the expression of ghrelin. Well-differentiated
      tumors had a significantly higher proportion of ghrelin-expressing cells than
      other types. CONCLUSION: Ghrelin expression correlated with tumor depth and tumor
      differentiation, suggesting an important role of ghrelin in tumor growth in ESCC.

PMID- 24922634
TI  - Decreased VDR expression in cutaneous melanomas as marker of tumor progression:
      new data and analyses.
AB  - BACKGROUND: Vitamin D3, acting via vitamin D receptor (VDR) affects a wide range
      of biological activities, including inhibition of proliferation and angiogenesis,
      with net antitumor effects. VDR expression is disturbed in many tumors, including
      melanomas. AIM: To find correlation between VDR expression in melanomas and
      prognostic biomarkers. MATERIALS AND METHODS: VDR was analyzed
      immunohistochemically in 69 cutaneous melanomas in relation to prognostic
      factors. RESULTS: Less advanced melanomas showed significantly higher VDR
      expression than the advanced stages. The presence of other markers such as
      ulceration and lack or non-brisk tumor infiltrating lymphocytes (TILs) was
      accompanied by significantly lower VDR expression. VDR expression also affected
      overall survival (OS) with most noticeable effect in the cases without
      ulceration. CONCLUSION: High VDR expression determines a less malignant phenotype
      and is related to better prognosis. Loss of VDR expression affects melanoma tumor
      behavior, allowing for progression of disease. VDR expression can also serve as a
      prognostic marker in routine histopathology evaluation.

PMID- 24922635
TI  - Collaborative network of predictive markers complicates formation of prognostic
      groups in patients with advanced lung cancer.
AB  - BACKGROUND: Evaluation of cancer therapies is mainly based on prolonging
      remission status and effect of survival. Various serological, clinical or
      histological markers are used to estimate the patient's prognosis, and to tailor
      specific therapies for patients with poor prognosis. However, it is still a
      challenge to combine all this information into a comprehensive risk prediction.
      PATIENTS AND METHODS: In 58 patients with advanced non small cell lung cancer we
      recorded 38 parameters (15 from clinic, 10 from histology, 13 from serology) to
      analyze their impact on survival. We both used univariate as well as multivariate
      approaches and decision tree analysis. RESULTS: Univariate analysis showed that
      ECOG status, stage, and the presence of cerebral or bone metastasis had a
      significant impact on survival, as well as the serum markers CA15-3, TPA, Cyfra.
      In a multivariate approach only ECOG and stage had a significant impact on
      survival. Considering correlation coefficients of >0.3 as an indicator of a
      functional relationship, we found several relations among the clinical (9),
      histological (8) or the serological parameters (13). Survival was related to 9
      parameters by significant direct and cross-relation coefficients. The use of
      already few variables with its different possible options led to many different
      patterns in the cohort, almost all being specific for individual patients, and
      thereby underlining their heterogeneity. Decision tree analysis revealed that by
      including either stage and kind of therapy or stage and expression of YB-1 allows
      to identify sub-groups with distinct prognosis. CONCLUSION: Clinical, serological
      and histological markers, all provide prognostic information. Because they are
      all linked in a collaborative network, the formation of homogenous prognostic
      groups by use of single markers is limited. Alternative statistical approaches
      with focus on decision trees may allow use of various information to assess
      individual patients into distinct risk groups.

PMID- 24922636
TI  - Immunohistochemical comparison of biomarker expression in biopsy and surgical
      specimens of non-small cell lung cancer.
AB  - BACKGROUND: Single tumors may show heterogeneity, and it is unclear whether
      biomarker expression in surgical and diagnostic biopsy samples correlates.
      MATERIALS AND METHODS: We retrospectively identified lung cancer patients who
      were diagnosed by biopsy and underwent surgery between January 2007 and October
      2010 at the Shimane University Hospital, Shimane, Japan. Thirty-two patients were
      identified. The expression of four predictive biomarkers was assessed, namely
      excision repair cross-complementing gene 1 (ERCC1), ribonucleotide diphosphate
      reductase M1 (RRM1), thymidylate synthase (TS), and class III beta-tubulin (BT).
      We also compared immunohistochemical staining in diagnostic biopsy and
      corresponding resected surgical samples. RESULTS: Moderate correlation was seen
      between the expression of ERCC1, RRM1, TS, and BT in the biopsy and surgical
      specimens, with r values of 0.512 (p=0.003), 0.411 (p=0.020), 0.475 (p=0.006),
      and 0.404 (p=0.027), respectively. CONCLUSION: Assessment of biopsy samples with
      immunohistochemical staining is a feasible and reliable method for use in
      clinical decision making.

PMID- 24922637
TI  - Diallyl disulfide inhibits TNFalpha-induced CCL2 release by MDA-MB-231 cells.
AB  - Monocyte chemotactic protein-1 (MCP-1/CCL2) is released by tumor tissues, serving
      as a potent chemokine enabling directional homing of mononuclear cells to tumor
      tissue, which subsequently differentiate into tumor-associated macrophages (TAMs)
      via TGFbeta1 signaling. TAMs readily invade tumor tissue and continue to
      synthesize pro-oncogenic proteins including tumor growth factors, matrix
      proteases (metastasis), angiogenic factors (neovascularization) and CCL2.
      Substances, which can attenuate or block the initial release of CCL2 have been
      shown to prevent cancer-associated inflammative pro-oncogenic processes. In the
      current study, we investigated the effects of the organosulfur compound diallyl
      disulfide (DADS), a natural constituent of Allium sativum (garlic) on suppression
      of TNFalpha-induced release of CCL2 from triple-negative human breast tumor (MDA
      MB-231) cells. Using an initial adipokine/chemokine protein panel microarray, the
      data show a predominant expression profile in resting/untreated MDA-MB-231 cells
      for sustained release of IL6, IL8, plasminogen Activator Inhibitor 1 and TIMP1/2.
      Treatment with TNFalpha (40 ng/ml) had no effect on many of these molecules, with
      a single major elevation in release of CCL2 (~1,300-fold up-regulation). TNFalpha
      induced CCL2 release was reversed by a sub-lethal concentration of DADS (100
      MUM), evident in antibody based assays. These findings provide evidence to
      support another avenue of anticancer/chemopreventative properties attributable to
      garlic constituents through immunomodulation. 

PMID- 24922638
TI  - The role of type D prostanoid receptors and PPARgamma in gastric cancer
      progression.
AB  - Prostaglandin D2 (PGD2) has been demonstrated to have antitumor effects on cancer
      cells. PGD2 acts through two major receptors of DP1 and DP2, as well as through
      the peroxisome proliferator-activated receptor gamma (PPARgamma) via the PGD2
      metabolite, 15-deoxy-Delta12-14-PGJ2. The expression levels of DP1, DP2, and
      PPARgamma were analyzed by immunohistochemistry on 277 primary gastric
      carcinomas. Either DP1- or DP2-positive cases were regarded as DP-positive. DP
      Positive tumour was significantly associated with lymph mode metastasis,
      lymphatic invasion, and venous invasion. PPARgamma positivity was not associated
      with any clinicopathological factors of gastric cancer. DP-Negative and PPARgamma
      positive cases were significantly associated with T category, lymph metastasis,
      and lymphatic invasion. The prognosis of DP-negative and PPARgamma-positive cases
      was better than that of the other cases. These findings suggest that DP and
      PPARgamma signaling influence the invasiveness of cancer cells. DP and PPARgamma
      can be used as a potential marker for gastric cancer progression. 

PMID- 24922639
TI  - Identification of metabolic signatures associated with erlotinib resistance of
      non-small cell lung cancer cells.
AB  - BACKGROUND/AIM: The acquisition of resistance to epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors (TKIs) remains a major challenge in lung cancer
      medicine. We sought to identify biomarkers for the early detection of resistance
      to TKIs. MATERIALS AND METHODS: Capillary electrophoresis time-of-flight mass
      spectrometry analysis was performed to identify the metabolic signatures
      associated with erlotinib resistance in erlotinib-resistant PC-9ER NSCLC cells
      established from the EGFR-mutant NSCLC cell line PC-9. RESULTS: PC-9ER cells
      showed metabolic signatures indicative of enhanced glutamine metabolism. Copy
      number gains in v-myc avian myelocytomatosis viral oncogene homolog (MYC),
      glutathione-S-transferase theta 2 (GSTT2), gamma-glutamyltransferase 1 (GGT1),
      and GGT5 were also detected, suggesting that amplification of these genes confers
      glutamine addiction in PC-9ER cells. CONCLUSION: Enhanced glutamine metabolism
      may be a surrogate marker that can be used to predict the likelihood of patients
      to respond to EGFR-TKIs.

PMID- 24922640
TI  - Cell-cycle analysis and apoptosis-associated proteins in cervical lesions of
      Brazilian women.
AB  - AIM: The aim of the present study was to detect the relative expressions of p53,
      p21(Waf1/Cip1), p27(Kip1) Bcl-2 and cleaved caspase-3 in cervical lesion samples
      from Brazilian women by immunohistochemistry. MATERIALS AND METHODS: A total of
      230 cervical biopsies in paraffin-embedded blocks were studied: 43 were invasive
      squamous cell carcinomas (SCC), 52 carcinomas in situ/cervical intraepithelial
      neoplasias III (CIN III), 54 cervical intraepithelial neoplasias II (CIN II), 51
      cervical intraepithelial neoplasias I (CIN I) and 30 non-neoplastic lesions (NN)
      with benign cellular changes. RESULTS: Significant differences were observed in
      the p53 expression between the different groups: NN and CIN I (p=0.010); NN and
      CIN II (p<0.00001); CIN II and CIN III (p=0.02); CIN II and CIS (p=0.0220); CIN
      II and CEC (p=0.010). Regarding p21(WAF1/Cip1), significant differences were
      observed between NN and CEC (p=0.001); CIN I and CEC (p=0.001); CIN II and CIN
      III (p=0,001); CIN II and CIS (p=0.0004) and CIN II and CEC (p<0.0001). For
      p27(Kip1), significant differences were observed between NN and CIN I
      (p<0.00001); NN and CIN II (p<0.00001); NN and CIS (p=0.038); CIN I and CIN III
      (p=0.001); CIN I and CIS (p=0.009); CIN I and CEC (p=0.0001); CIN II and CIN III
      (p=0.0003); CIN II and CIS (p=0.002); CIN II and CEC (p< 0.00001). Bcl-2 and
      caspase-3 did not show remarkable differences between groups. CONCLUSION: p53,
      p21(WAF1/CIP1), p27(KIP1) appear to be involved in the course of carcinogenesis.
      Rare expression of Bcl-2 and cleaved caspase-3 suggests that these proteins
      probably do not participate in cervical apoptosis.

PMID- 24922641
TI  - Heparanase and COX-2 expression as predictors of lymph node metastasis in large,
      high-grade breast tumors.
AB  - BACKGROUND/AIM: Heparanase (HPA) contributes to breast cancer metastasis by
      facilitating the breakdown of the basement membrane and extracellular matrix.
      High expression of HPA is thought to be associated with increased nodal
      involvement and poor survival in patients with breast cancer. Overexpression of
      cyclooxygenase-2 (COX-2) in breast cancer is associated with indicators of poor
      prognosis such as lymph node metastasis, poor differentiation, and large tumor
      size. The underlying mechanism by which HPA and COX-2 overexpression increases
      the metastatic potential of breast cancer is not fully-understood. To enhance our
      understanding over these mechanisms, we aimed to investigate the relationship
      between the size of the tumor and HPA expression, tumor grade as well as lymph
      node status in patients with breast cancer. MATERIALS AND METHODS:
      Immunohistochemical analysis of HPA and COX-2 expression was performed on 246
      breast tumor samples. The expression of HPA was correlated with COX-2 expression,
      tumor grade, lymph node status, oestrogen receptor status. RESULTS: The
      overexpression of HPA and COX-2 was associated with increased likelihood of lymph
      node positivity in large, high-grade tumors. High-grade tumors with size greater
      than 20 mm, that overexpressed HPA, were 4-times more likely to be associated
      with lymph node involvement (OR 4.71, CI 1.21-18.25). Whereas, tumors greater
      than 20 mm in size were 5-times more likely to metastasize to the regional lymph
      nodes, if associated with overexpression of COX-2 (OR 5.5, CI 1.2-24.8).
      CONCLUSION: Expression of HPA appears to be a key mechanism by which large, high
      grade breast tumors metastasize to regional lymph nodes, while COX-2
      overexpression may be an independent predictor of lymph node positivity.

PMID- 24922642
TI  - Predicting the sensitivity to ion therapy based on the response to photon
      irradiation--experimental evidence and mathematical modelling.
AB  - BACKGROUND/AIM: The use of ion radiation therapy is growing due to the
      continuously increasing positive clinical experience obtained. Therefore, there
      is a high interest in radio-biological experiments comparing the relative
      efficiency in cell killing of ions and photons as photons are currently the main
      radiation modality used for cancer treatment. This comparison is particularly
      important since the treatment planning systems (TPSs) used at the main ion
      therapy Centers make use of parameters describing the cellular response to
      photons, respectively ions, determined in vitro. It was, therefore, the aim of
      this article to compare the effects of high linear energy transfer (LET) ion
      radiation with low LET photons and determine whether the cellular response to low
      LET could predict the response to high LET irradiation. MATERIALS AND METHODS:
      Clonogenic cell survival data of five tumor cell lines irradiated with different
      ion beams of similar, clinically-relevant, LET were studied in relation to
      response to low LET photons. Two mathematical models were used to fit the data,
      the repairable-conditionally repairable damage (RCR) model and the linear
      quadratic (LQ) model. RESULTS: The results indicate that the relative biological
      efficiency of the high LET radiation assessed with the RCR model could be
      predicted based only on the response to the low LET irradiation. CONCLUSION: The
      particular features of the RCR model indicate that tumor cells showing a large
      capacity for repairing the damage will have the larger benefit from radiation
      therapy with ion beams.

PMID- 24922643
TI  - Development of a dihydroartemisinin-resistant Molt-4 leukemia cell line.
AB  - Artemisinin generates cytotoxic free radicals when it reacts with iron. Its
      toxicity is more selective toward cancer cells because cancer cells contain a
      higher level of intracellular-free iron. We previously reported that
      dihydroartemisinin (DHA), an active metabolite of artemisinin, has selective
      cytotoxicity toward Molt-4 human lymphoblastoid cells. A concern is whether
      cancer cells could develop resistance to DHA after repeated administration, thus
      limiting its therapeutic efficacy. In the present study, we developed a DHA
      resistant Molt-4 cell line (RTN) by exposing Molt-4 cells to gradually increasing
      concentrations of DHA in vitro. The half-maximal inhibitory concentration (IC50)
      of DHA for RTN cells is 7.1-times higher than that of Molt-4 cells. RTN cells
      have a higher growth rate than Molt-4 cells. In addition, we investigated the
      toxicities of two more potent synthetic artemisinin compounds, artemisinin dimer
      alcohol and artemisinin-tagged holotransferrin toward RTN cells; RTN cells showed
      no significant cross-resistance to these compounds. 

PMID- 24922644
TI  - Influence of hypoxia inducible factors on the immune microenvironment in ovarian
      cancer.
AB  - BACKGROUND: Ovarian tumors remain immunogenic even at advanced stages, but cancer
      induced immunosuppression abrogates immune surveillance. The composition of the
      immune microenvironment in ovarian tumors was characterized by analyzing selected
      immunosuppressive factors in specimens from cancer patients. The influence of the
      hypoxia inducible factors on the immune microenvironment was also addressed.
      MATERIALS AND METHODS: Tumor tissue was collected from 21 ovarian cancer patients
      immediately following tumor excision during surgery. The mRNA expression of
      selected genes was quantified, and tumor infiltrating leukocytes were
      characterized by flow cytometry to identify regulatory T-cells, myeloid-derived
      suppressor cells, and type-2 macrophages. RESULTS: Overall, a pronounced
      heterogeneity was found among the analyzed samples. Nevertheless, statistical
      analysis revealed that the expression of hypoxia inducible factors correlated
      with the transcription levels of several immunosuppressive molecules. CONCLUSION:
      The activity of hypoxia inducible factors contributes to cancer immunosuppression
      in ovarian cancer patients.

PMID- 24922645
TI  - SOD3 acts as a tumor suppressor in PC-3 prostate cancer cells via hydrogen
      peroxide accumulation.
AB  - BACKGROUND: The functions of superoxide dismutase-3 (SOD3), which acts on the
      cell surface and protects cells from oxidative stress, remain uncertain in the
      progression of prostate cancer. MATERIALS AND METHODS: To verify SOD3 expression
      in human prostate tissue, immunohistochemistry was performed using tissue
      microarrays. To investigate the effects of SOD3 on proliferation, migration, and
      invasion, SOD3 was overexpressed and recombinant SOD3 was employed in PC-3
      prostate cancer cells. H2O2 levels, reduced glutathione (GSH)/oxidized
      glutathione (GSSG) ratio, catalase activity, and 8-oxo-2'-deoxyguanosine (8-OHdG)
      were estimated in SOD3-overexpressing PC-3 cells. RESULTS: Immunohistochemistry
      revealed reduced expression of SOD3 in prostate cancer tissue. SOD3
      overexpression in PC-3 cells inhibited cell proliferation, migration, and
      invasion. Recombinant SOD3 had the same effect. H2O2 accumulation was increased
      by SOD3 overexpression, GSH/GSSG ratio was decreased, and catalase activity was
      decreased. DNA damage in SOD3-overexpressing cells was confirmed by 8-OHdG
      elevation. CONCLUSION: Since SOD3 acts as a tumor suppressor, SOD3 overexpression
      and recombinant SOD3 might lead to treatment for prostate cancer.

PMID- 24922646
TI  - HSPA2 is expressed in human tumors and correlates with clinical features in non
      small cell lung carcinoma patients.
AB  - BACKGROUND/AIM: It has been shown that HSPA2 protein, a testis-enriched member of
      HSPA/HSP70 family, is important for cancer cell growth and metastasis. However,
      the status of HSPA2 expression in tumors and its clinical/prognostic significance
      are obscure. Herein we aimed to investigate the expression of HSPA2 in various
      types of tumors and to determine the possible clinical and prognostic
      significance of HSPA2 in non-small cell lung carcinoma (NSCLC). MATERIALS AND
      METHODS: Tissue microarrays and postoperative NSCLC tumors were tested for HSPA2
      by immunohistochemistry. RESULTS: HSPA2 is expressed in the majority of tumor
      histotypes. In NSCLC patients (n=85), nuclear HSPA2 expression was associated
      with histology, TNM staging and prognosis. High HSPA2 expression was
      significantly related to shorter overall survival (OS) in stage I-II patients. In
      multivariate analysis, high HSPA2, together with stage IIIA and male sex, were
      associated with shorter OS in the whole group. CONCLUSIONS: As exemplified in
      NSCLC the status of HSPA2 in human tumors may have certain prognostic
      significance.

PMID- 24922647
TI  - Primary and secondary resistance to tyrosine kinase inhibitors in lung cancer.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKI) have emerged as important
      therapeutic agents for the treatment of several types of cancer including lung
      cancer. Recent research attempts show that only a small population of cancer
      patients responds to TKI and furthermore, these patients eventually develop
      resistance. Studies support the classification of resistance in primary and
      secondary resistance. MATERIALS AND METHODS: In the present study the
      differentiation between primary and secondary resistance to TKI in lung cancer
      cell lines was investigated. Lung cancer cell lines were tested for viability,
      apoptosis and cell cycle after exposure to the TKI erlotinib and gefitinib.
      RESULTS: Cells with primary resistance showed similar cell-cycle patterns to
      those with secondary resistance but differences were observed between the two
      groups in the viability and apoptosis assays. CONCLUSION: Understanding the
      effects of TKI on cell signaling pathways would shed light on the mechanisms of
      acquired resistance and the differences between primary and secondary resistance.

PMID- 24922648
TI  - The role of claudin-1 and claudin-7 in cervical tumorigenesis.
AB  - BACKGROUND/AIM: The claudin family of proteins are key constituents of tight
      junctions and the aberrant expression of these proteins can contribute to de
      stabilisation of tight junctions and thus to loss of cell polarity and cohesion.
      Increased expression of claudin-1 and claudin-7 has been observed in pre-invasive
      cervical lesions and cervical carcinomas. The present study attempted to assess
      the effect of claudin-1 and claudin-7 overexpression on the HeLa cervical
      carcinoma cell line, in terms of cell proliferation/viability, permeability,
      invasion and migration. MATERIALS AND METHODS: HeLa cells were stably transfected
      with expression vectors containing the claudin-1 and claudin-7 genes to produce
      two separate stable cell lines expressing claudin-1 and claudin-7, respectively.
      The stable cell lines were examined with regard to their invasion and migration
      abilities, cell permeability and cell proliferation/viability and compared to non
      claudin-1 or -7 transfected HeLa. RESULTS: The present study found that claudin-1
      and claudin-7 affected the migratory ability of HeLa cells, reducing their
      ability to migrate in a gap closure assay compared to non-claudin-transfected
      HeLa cells. Monolayers of claudin-1 and claudin-7 transfected cells also
      displayed an increased transepithelial electrical resistance indicating decreased
      permeability compared to non-claudin-transfected HeLa. The study found that
      claudin-1 or claudin-7 expression had no effect on the proliferation or viability
      of HeLa cells. Claudin-1 or -7 expression also did not affect the invasive
      ability of HeLa cells with both stable cells lines and non-claudin-transfected
      HeLa cells all showing low invasive ability. CONCLUSION: The results of the
      present study indicate that claudin-1 and claudin-7 overexpression alone does not
      contribute to increased tumorigenesis in cervical carcinoma, instead claudin-1
      and - 7 expression in HeLa cells contribute to reducing the migratory ability of
      cells and decrease their permeability.

PMID- 24922649
TI  - Spontaneous in vitro senescence of glioma cells confirmed by an antibody against
      IDH1R132H.
AB  - BACKGROUND: We have recently suggested that glioblastoma cells become
      spontaneously senescent in cell culture conditions. The antibody specific against
      IDH1(R132H) offers the perfect opportunity to verify this hypothesis. MATERIALS
      AND METHODS: We analyzed the features of senescence in 8 glioma cell cultures
      showing the IDH1(R132H) mutation based on combination of immunocytochemistry,
      enzymo-cytochemistry, BrdU incorporation assay and real-time microscopic
      observation. RESULTS: We report that glioma cells showing the IDH1(R132H)
      mutation become rapidly and spontaneously senescent in vitro. Senescence was
      observed in both classical and novel serum-free cell culture conditions.
      Importantly, the senescent IDH1(R132H)-positive cells showed the expression of
      stemness marker (SOX2). CONCLUSION: In vitro senescence appeared to be the main
      reason of the difficulties in any kind culturing of glioma cells. 3D cell
      cultures prolonged the survival and in vitro proliferation of neoplastic
      IDH1(R132H)-positive cells, however, did not enhance the stabilization
      efficiency. Senescence of glioma cells is spontaneously triggered in vitro, which
      offers the opportunity of potential new therapeutic strategies based on this
      phenomenon.

PMID- 24922650
TI  - Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3
      signaling in HER2-overexpressing MDA-MB-453 breast cancer cells.
AB  - BACKGROUND: This study aimed to examine the effect of apigenin on proliferation
      and apoptosis in HER2-overexpressing MDA-MB-453 breast cancer cells. MATERIALS
      AND METHODS: The antiproliferative effects of apigenin were examined by
      proliferation and MTT assays. The effect of apigenin on apoptotic molecules was
      determined by western blotting. RT-PCR was performed to measure mRNA levels of
      HIF-1alpha and VEGF. ELISA assay was performed to measure intracellular VEGF
      levels. Immunocytochemistry was performed to evaluate nuclear STAT3 level.
      RESULTS: Apigenin inhibited the proliferation of MDA-MB-453 cells. Apigenin up
      regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage
      of PARP. Apigenin induced extrinsic apoptosis and blocked the activation
      (phosphorylation) of JAK2 and STAT3. Apigenin inhibited CoCl2-induced VEGF
      secretion and decreased the nuclear staining of STAT3. CONCLUSION: Apigenin
      exerts its antiproliferative activity by inhibiting STAT3 signaling. Apigenin
      could serve as a useful compound to prevent or treat HER2-overexpressing breast
      cancer.

PMID- 24922651
TI  - Effects of targeting endometrial stromal sarcoma cells via histone deacetylase
      and PI3K/AKT/mTOR signaling.
AB  - AIM: Endometrial stromal sarcoma (ESS) is a rare gynecological mesenchymal
      malignancy with only few therapeutic options. This study aimed to investigate the
      efficacy of the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid
      (SAHA) combined with inhibitors of the phosphoinositid-3-Kinase (PI3K) pathway in
      ESS therapy. MATERIALS AND METHODS: The effects of SAHA combined with inhibitor
      of PI3K (LY294002, LY), mammalian target of rapamycin mTOR (rapamycin), and their
      combination on cell growth and the PI3K pathway in two ESS cell lines (ESS-1 and
      MES-SA) and one non-neoplastic cell line HESC, were investigated. RESULTS: SAHA
      reduced growth of the three cell lines by inhibiting protein kinase B AKT and
      mTOR/p70S6K cascade activation. SAHA combined with LY or rapamycin, or both,
      synergistically reduced p-p70S6K and p-4E-BP1 levels. SAHA combined with LY and
      rapamycin led to the strongest growth inhibition and slowest growth recovery
      among the combination treatments. CONCLUSION: SAHA combined with inhibition of
      PI3K and mTOR could represent an efficient therapy option for patients with ESS.

PMID- 24922652
TI  - Preconditioning with hyperbaric oxygen in pancreaticoduodenectomy: a randomized
      double-blind pilot study.
AB  - In a prospective randomized double-blind study, we evaluated the post-operative
      biological and clinical effects of a single preoperative hyperbaric-treatment the
      day before surgery for pancreatic ductal adenocarcinoma. PATIENTS AND METHODS:
      Twenty one patients were randomized and divided into two groups: group-A (10
      patients, 48%) were exposed to a HyperBaric Oxygen (HBO) session the day before
      intervention [Pre-Intervention Day (PID)], group-B (11 patients, 52%) breathed
      air for 40 min in a hyperbaric chamber pressurized to 1.15 ATA (placebo group).
      For all patients blood samples were obtained before HBO treatment or the placebo
      procedure (T0); at the end of HBO session or placebo procedure (T1); on the first
      post-operative day (POD)(T2) and on seventh POD(T3) day, measuring interleukin
      (IL)-1, IL-6, IL-8, IL-10, IL-12 and TNF-alpha, recording postoperative
      pancreatic fistula (POPF), biliary-fistula, fever, intra-abdominal abscess,
      bleeding, pulmonary complications, delayed gastric emptying and requirement for
      post-operative antibiotics. The results of the present pilot study suggest that a
      single preoperative hyperbaric oxygen treatment on the day before surgery may
      reduce the complication rate in pancreatic resection.

PMID- 24922653
TI  - Cell-cycle distribution and Thymidilate Synthatase (TS) expression correlate with
      5-FU resistance in head and neck carcinoma cells.
AB  - BACKGROUND: Acquired chemoresistance to 5-fluorouracil (5-FU) remains one of the
      obstacles for the success of 5-FU-based cancer chemotherapy, and some molecular
      mechanisms of acquired 5-FU resistance are still unknown. The main action of 5-FU
      is the suppression of DNA replication by inhibiting Thymidylate Synthase (TS).
      MATERIALS AND METHODS: We analyzed 5-FU resistance mechanisms using the head and
      neck squamous cell carcinoma cell lines, UM-SCC-23, and two different resistant
      cell lines, UM-SCC-23/WR and UM-SCC-23/MR, which were procured from UM-SCC-23
      cells. To acquire resistance, the two cells underwent repeated treatment of 5-FU
      with different durations and frequency. We determined differences in the cell
      cycle distribution and the expression of TS proteins in the three cell lines.
      Moreover, cell-cycle distribution in cells which acquired resistance after 5-FU
      treatment, was compared to that of parental cells, using flow cytometric
      analysis. RESULTS: There was a remarkable increase in TS protein expression
      levels in UM-SCC-23/WR following 5-FU treatment. S-phase cells of UM-SCC-23 and
      UM-SCC-23/WR cells were immediately increased after treatment with 5-FU, whereas
      UM-SCC-23/MR were accumulated to the S-phase slightly later. CONCLUSION: The cell
      cycle perturbation or elevation of TS protein expression may be involved in
      acquired 5-FU resistance and identifies 5-FU resistance mechanisms in the two
      different 5-FU treatment regimens.

PMID- 24922654
TI  - Effect of EPH-ephrin signaling on the growth of human leukemia cells.
AB  - BACKGROUND: Signaling induced by binding of erythropoietin-producing hepatoma
      amplified sequence (EPH) receptors to their cell-surface ephrin ligands is
      implicated in hematopoiesis and growth of various cancer cells. However, the
      roles of EPH-ephrin signaling in leukemia have not been elucidated. We
      investigated the effects of EPHB4 and ephrin B2 on the growth of leukemia cells.
      MATERIALS AND METHODS: Seven human leukemia cell lines were used to examine the
      effects of recombinant ephrin B2 and EPHB4 on cell proliferation by colorimetric
      WST-1 assay and colony assays; on protein tyrosine phosphorylation; and on mRNA
      expression by reverse transcription-polymerase chain reaction and microarray
      analysis. RESULTS: In an erythroid leukemia-derived cell line AA, exogenous
      ephrin B2 induced proliferation and colony formation; in addition, it up
      regulated protein tyrosine phosphorylation and the expression of growth-related
      genes such as FBJ murine osteosarcoma viral oncogene homolog B and v-src avian
      sarcoma viral oncogene homolog. CONCLUSION: Growth-promoting effects of ephrin B2
      were observed in an erythroid leukemia cell line, suggesting that the EPH-ephrin
      signaling may be involved in the pathology of leukemia.

PMID- 24922655
TI  - PPM1D as a novel biomarker for prostate cancer after radical prostatectomy.
AB  - Protein phosphatase magnesium-dependent 1 delta (PPM1D) is involved in several
      types of cancer. The current study examined the role of PPM1D expression in
      prostate cancer (PCa) tissues and in PCa cell lines. Expression of PPM1D was
      evaluated using immunohistochemistry in 234 PCa tissues after radical
      prostatectomy and 80 benign prostatic hyperplasia (BPH) tissues. The associations
      of PPM1D expression with clinicopathological parameters and survival were
      analyzed. In vitro, tumor cells were transfected with small interfering RNA
      targeting PPM1D (siPPM1D) or si-Scramble, and the cell proliferation, migration
      and invasion were determined. We found that PPM1D expression was significantly
      higher in PCa tissues than that in BPH tissues. PPM1D expression was positively
      correlated with Gleason score (p=0.022), T stage (p=0.015) and lymph node status
      (p=0.016). Kaplan-Meier curve analysis showed that patients with positive PPM1D
      expression had shorter biochemical recurrence-free survival and overall survival.
      Furthermore, multivariate analyses showed that PPM1D expression was an
      independent predictor of both biochemical recurrence-free (hazard ratio=3.437,
      95% confidence interval=1.154-6.209, p=0.016) and overall survival (hazard
      ratio=5.026, 95% confidence interval=2.545-8.109, p=0.007). Knockdown of PPM1D
      inhibited the proliferation, migration and invasion capabilities of PC-3 and
      LNCaP cells. PPM1D expression may predict for both overall and biochemical
      recurrence-free survival in patients after radical prostatectomy for PCa.
      Elevated PPM1D expression plays a key role in progression of PCa. 

PMID- 24922656
TI  - RAD001 enhances the radiosensitivity of SCC4 oral cancer cells by inducing cell
      cycle arrest at the G2/M checkpoint.
AB  - BACKGROUND: Inhibition of mammalian target of rapamycin (mTOR) kinase enhances
      the radiosensitivity of some cancer cells. We investigated the effect of RAD001,
      an mTOR inhibitor, on irradiated oral cancer cell lines. MATERIALS AND METHODS:
      Clonogenic assays were performed to determine the radiosensitivity of SCC4 and
      SCC25 cells after treatment with RAD001. Target protein phosphorylation,
      apoptosis, and cell-cycle progression were assessed in SCC4 cells treated with
      RAD001 with and without ionizing radiation. RESULTS: RAD001 increased the
      radiosensitivity of SCC4 cells without affecting cell death; it also inhibited
      phosphorylation of mTOR, S6, and factor 4E binding protein 1 and reduced the
      clonogenic survival of irradiated cancer cells. RAD001 combined with radiation
      increased G2 arrest by activating CHK1, which phosphorylates CDC25C at Ser216,
      thereby inhibiting CDC2-cyclin B 1 complex formation. CONCLUSION: RAD001 enhances
      the radiosensitivity of SCC4 cells by inhibiting mTOR signaling and inducing G2
      cell-cycle arrest through disruption of the G2 checkpoint.

PMID- 24922657
TI  - Pattern of somatostatin receptors expression in normal and bladder cancer tissue
      samples.
AB  - BACKGROUND/AIM: Known risks factors for bladder cancer progression and recurrence
      are limited regarding their prognostic ability. Therefore identification of
      molecular determinants of disease progression could provide with more specific
      prognostic information and could be translated into new approaches for biomarker
      development. In the present study we evaluated, the expression patterns of
      somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. MATERIALS
      AND METHODS: The expression of SSTR1-5 was characterized in 45 normal and bladder
      cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT
      PCR). RESULTS: SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4
      in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed
      lower levels of SSTR3. Co-expression of SSTRs was associated with superficial
      disease. CONCLUSION: Our results demonstrate, for the first time, that there is
      expression of SSTR in normal and bladder cancer urothelium. Further studies are
      required to evaluate the prognostic and therapeutic significance of these
      findings.

PMID- 24922658
TI  - Genetic polymorphism of miR-196a as a prognostic biomarker for early breast
      cancer.
AB  - BACKGROUND: As microRNAs (miRNA) may play important roles in tumorigenesis by
      regulating the expression of proto-oncogenes or tumor suppressor genes, the
      present study analyzed single nucleotide polymorphisms (SNPs) located in miRNA
      and miRNA-binding sites of various genes and their impact on prognosis for 452
      patients with early breast cancer. MATERIALS AND METHODS: Three SNPs of miR-196a
      (rs3746444, rs11614913, and rs1044129) were selected using in silico analysis and
      genotyped using the Sequenom MassARRAY. RESULTS: The median age of patients was
      48 years, and 283 (62.6%) were estrogen and/or progesterone receptor (ER/PgR)
      positive, 86 (19.0 %) had human epidermal growth factor receptor 2 (HER2)
      overexpressing, and 77 (17.0%) had triple-negative early breast cancer. During
      the median follow-up of 6.9 years, 67 (14.8%) relapses and 55 (12.2%) deaths were
      recorded. Among the three polymorphisms, the C allele of miR-196a rs11614913T>C
      was significantly associated with worse disease-free (DFS) and distant DFS (DDFS)
      when adjusted for clinical and pathological parameters. In particular, the
      prognostic impact of rs11614913 was limited to the hormone receptor-expressing
      subtype, where the patients bearing the CC genotype showed worse survival in
      terms of DFS and DDFS compared with the patients with the TT or TC genotype as a
      recessive model (hazard ratio=2.610, p=0.003 for DFS; hazard ratio=2.730, p=0.013
      for DDFS). CONCLUSION: The current study provides evidence that the miR-196a
      rs11614913T>C polymorphisms are possible prognostic biomarker for patients with
      hormone receptor-expressing early breast cancer.

PMID- 24922659
TI  - Contribution of DNA double-strand break repair gene XRCC3 genotypes to oral
      cancer susceptibility in Taiwan.
AB  - The DNA repair gene X-ray repair cross complementing protein 3 (XRCC3) is thought
      to play a major role in double-strand break repair and in maintaining genomic
      stability. Very possibly, defective double-strand break repair of cells can lead
      to carcinogenesis. Therefore, a case-control study was performed to reveal the
      contribution of XRCC3 genotypes to individual oral cancer susceptibility. In this
      hospital-based research, the association of XRCC3 rs1799794, rs45603942,
      rs861530, rs3212057, rs1799796, rs861539, rs28903081 genotypes with oral cancer
      risk in a Taiwanese population was investigated. In total, 788 patients with oral
      cancer and 956 age- and gender-matched healthy controls were genotyped. The
      results showed that there was significant differential distribution among oral
      cancer and controls in the genotypic (p=0.001428) and allelic (p=0.0013)
      frequencies of XRCC3 rs861539. As for the other polymorphisms, there was no
      difference between case and control groups. In gene-lifestyle interaction
      analysis, we have provided the first evidence showing that there is an obvious
      joint effect of XRCC3 rs861539 genotype with individual areca chewing habits on
      oral cancer risk. In conclusion, the T allele of XRCC3 rs861539, which has an
      interaction with areca chewing habit in oral carcinogenesis, may be an early
      marker for oral cancer in Taiwanese. 

PMID- 24922660
TI  - Hyperoxia resensitizes chemoresistant glioblastoma cells to temozolomide through
      unfolded protein response.
AB  - BACKGROUND: Intratumoural hypoxia is associated with chemoresistance in
      glioblastoma multiforme (GBM), a highly malignant brain tumour. Adaptive response
      to endoplasmic reticulum stress induced by temozolomide is a major obstacle in
      recurrent GBM. We investigated whether hyperoxia resensitizes temozolomide
      resistant GBM cells to temozolomide by abrogating the hypoxia-induced, unfolded
      protein response (UPR)-related protective mechanisms. MATERIALS AND METHODS: We
      examined changes to key UPR modulators in temozolomide-sensitive and -resistant
      human GBM cells (D54 and U87) treated with/without temozolomide at different
      oxygen concentrations using western blotting, and cytotoxic benefits of
      overexpressing key chaperone, P4HB, in GBM cells (U87 and U251) under normoxia
      and hyperoxia. RESULTS: Hyperoxia, alone or synergistically with temozolomide,
      activated the UPR in sensitive and resistant D54 and U87 cell lines. Hyperoxia
      also reduced survival benefit of U87 and U251 cells with P4HB overexpression
      through the UPR. CONCLUSION: Hyperoxia enhanced GBM cell sensitivity to
      temozolomide, likely through UPR, highlighting an important treatment modality
      targeting chemosensitive and -resistant GBM.

PMID- 24922661
TI  - The steroidal Na+/K+ ATPase inhibitor 3-[(R)-3-pyrrolidinyl]oxime derivative (3-R
      POD) induces potent pro-apoptotic responses in colonic tumor cells.
AB  - Recently, potent anticancer actions of the steroidal Na(+)/K(+) ATPase inhibitor
      3-[(R)-3-pyrrolidinyl]oxime derivative 3 (3-R-POD) have been reported for
      multiple cell lines, including prostate and lung cancer cells. In the present
      study, the anticancer action of 3-R-POD was addressed in colonic tumor cells.
      Treatment of Caco2 colonic tumor cells with increasing concentrations of 3-R-POD
      induced potent, dose-dependent inhibition of cell growth as measured by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In
      addition, the APOpercentage apoptosis assay revealed significant pro-apoptotic
      responses, suggesting that the anticancer activity of this steroidal Na(+)/K(+)
      ATPase inhibitor in colonic tumors takes places mainly through the induction of
      strong pro-apoptotic effects. Focussing on the molecular mechanism that may
      regulate these interactions, 3-R-POD was shown to induce significant early actin
      re-organization and late Protein Kinase B (AKT) de-phosphorylation. Finally, the
      3-R-POD-induced inhibition of cell growth and early actin reorganization in
      colonic cancer cells remained unchanged when cells were pre-treated with
      pertussis toxin, thus excluding possible interactions of this inhibitor with G
      coupled receptors. These results indicate that 3-R-POD induces potent pro
      apoptotic responses in colonic tumor cells governed by actin re-organization and
      inhibition of AKT pro-survival signaling. 

PMID- 24922662
TI  - FIP-gts potentiate autophagic cell death against cisplatin-resistant urothelial
      cancer cells.
AB  - BACKGROUND: Urothelial cancer (UC) is a common cancer among males. Once
      metastatic or chemoresistant diseases develop, there is little effective
      treatment available. A fungal immunomodulatory protein, ganoderma tsugae (FIP
      gts) possesses antitumor activity against solid tumors and inhibits telomerase
      activity. FIP-gts induces autophagy in cancer cells and may provide an
      alternative pathway against chemo-resistance. MATERIALS AND METHODS: Two UC cell
      lines were used to investigate the cytotoxicity effects and the autophagy
      regulation of FIP-gts using flow cytometry, acidic vesicular organelles (AVO)
      staining and western blotting. RESULTS: MTT assay showed that FIP-gts and
      bafilomycin-A1 (Baf-A1) and or chloroquine (CQ) could enhance a significantly
      synergistic cytotoxicity. The treatment of UC cell lines with FIP-gts activated
      LC-3 II formation and AVO positive staining on western blot and flow cytometry.
      Interestingly, FIP-gts and Baf-A1 combined treatment was found to lead to
      enhancement of apoptosis along with inhibition of autophagy in parental and
      resistant UC cells. CONCLUSION: FIP-gts may have the potential to be utilized as
      a therapeutic adjuvant for the treatment of resistant UC cancer down-regulating
      Beclin-1 to activate autophagic cell death.

PMID- 24922663
TI  - DNA methylation in paired breast epithelial and white blood cells from women
      undergoing reduction mammoplasty.
AB  - BACKGROUND: The extent to which white blood cell (WBC) DNA methylation provides
      information on the status of breast epithelial cell DNA is unknown. PATIENTS AND
      METHODS: We examined the correlation between methylation in Ras-association
      domain family-1 gene (RASSF1), a tumor-suppressor gene, and methylation in
      repetitive elements in paired sets of DNA from WBC and breast epithelial cells
      collected from 32 women undergoing reduction mammoplasty. RESULTS: We observed no
      evidence of correlation in methylation levels for ALU, long interspersed nuclear
      element-1 (LINE1) or juxtacentromeric satellite-2 (SAT2) (r=0.02 for LINE1,
      p=0.98; r=0.28 for ALU, p=0.12; r=0.26 for SAT2, p=0.17) for matched sets of DNA
      from WBC and breast epithelial cells. Variability in these markers across
      individuals and in the same tissue was low. Five women had an average methylation
      level above 5% for RASSF1 in breast epithelial cell DNA; however, average
      methylation levels in WBC DNA for these women were all below 1%. CONCLUSION:
      Methylation patterns in WBC DNA did not reflect methylation patterns in the
      breast.

PMID- 24922664
TI  - Insulin-like growth factor receptor 1 mRNA expression as a prognostic marker in
      advanced non-small cell lung cancer.
AB  - BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be
      established as a biomarker in non-small cell lung cancer (NSCLC) but could prove
      useful in customized chemotherapy. We explored its prognostic value using both
      quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR)
      and immunohistochemistry (IHC). MATERIALS AND METHODS: Analyses of IGF1R were
      performed on patients with advanced NSCLC, included in a randomized chemotherapy
      trial, having large, representative tissue samples. IGF1R mRNA and protein
      expression were correlated to clinical end-points. RESULTS: Surgical tissue
      samples were available from 33 patients deemed inoperable. IGF1R status varied
      according to histopathology. Patients with tumors positive for IGF1R mRNA
      expression had a shorter progression-free and overall survival when compared to
      the negative sub-group (6.1 vs. 7.4 months, p=0.039 and 10.9 vs. 14.3 months,
      p=0.038, respectively). IGF1R protein expression showed a similar, although non
      significant tendency. CONCLUSION: IGF1R mRNA expression may be a prognostic
      biomarker in advanced NSCLC and should be investigated in a larger population.

PMID- 24922665
TI  - Preliminary clinical outcomes of image-guided 3-dimensional conformal
      radiotherapy for limited brain metastases instead of stereotactic irradiation
      referral.
AB  - To determine the preliminary clinical outcomes of image-guided 3-dimensional
      conformal radiotherapy (IG-3DCRT) for limited but variably-sized brain metastases
      (BM). Sixty-two lesions in 24 patients were retrospectively evaluated; out of
      these patients 75% were >= 65 years of age, and 37.5% were categorized into
      recursive partitioning analysis (RPA) class 3. The median value for the maximum
      diameter of the lesions was 19 mm (range=4-72 mm). The median sole treatment dose
      was 36 Gy in 10 fractions. The median survival durations after IG-3DCRT were 12.0
      months and 3.2 months for patients categorized into RPA classes <= 2 and 3,
      respectively. Local recurrences occurred in two lesions with a 6-month local
      control probability of 93.0%. Major toxicities included radiation necrosis in two
      patients. IG-3DCRT is feasible even for patients with limited BM who are
      categorized into RPA class 3, and confers clinical outcomes comparable to those
      of stereotactic radiosurgery, including excellent local control and minimal
      toxicity even for large tumors.

PMID- 24922666
TI  - An additional case of gastric serrated adenoma.
AB  - Gastric serrated adenoma is an apparently rare adenoma phenotype characterized by
      branched villi exhibiting lateral saw-tooth indentations lined with dysplastic
      cells. Out of the 21 gastric serrated adenomas now in record, including the case
      reported here, 76% (n=16) exhibited invasive carcinoma. In contrast, only 15% of
      the gastric tubular/villous (that is, non-serrated) adenomas reported in the
      literature revealed invasive growth. Although the cause for the virulent
      behaviour of gastric serrated adenomas remains elusive, it would appear that not
      only the degree of severity of the cellular dysplasia but also the serrated
      ornamental configurations might play a particular role in the unusual virulence
      of these adenomas. 

PMID- 24922667
TI  - Survival and prognostic factors in pancreatic and ampullary cancer.
AB  - AIM: We analyzed survival of patients diagnosed with ampullary cancer (AC) and
      pancreatic ductal adenocarcinomas (PDAC). PATIENTS AND METHODS: Between 1996 and
      2009, 505 and 69 patients diagnosed with PDAC and AC, respectively, were
      identified. Overall survival was analyzed according to tumor entity, therapeutic
      approach and pathological tumor stage. RESULTS: The 5-year overall survival rate
      of patients with AC (37%; 95% confidence interval 25-49%) was remarkably higher
      compared to PDAC patients (7%; 95% confidence interval 5-10%). In both cohorts,
      surgical resection improved survival. Analysis of pathological factors revealed a
      survival benefit for patients staged with small primary tumors (pT1/2) and
      exclusion of distant metastases (M0) for both PDAC and AC. Interestingly, absence
      of lymph node metastasis substantially improved survival in AC, but not in PDAC.
      CONCLUSION: Overall survival of patients with AC is superior compared to that of
      patients with PDAC. Therapeutically, adequate regional lymph node dissection
      seems particularly important for the surgical management of AC.

PMID- 24922669
TI  - XRCC1 rs25487 polymorphism predicts the survival of patients after postoperative
      radiotherapy and adjuvant chemotherapy for breast cancer.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in a DNA-repair gene, X-Ray
      repair cross complementing group 1 (XRCC1), have been associated with the
      survival of patients with breast cancer. We investigated the predictive value of
      XRCC1 SNP (rs25487) in patients with early breast cancer. PATIENTS AND METHODS:
      The XRCC1 rs25487 genotypes of 411 Finnish patients with breast cancer were
      analyzed by a polymerase chain reaction-restriction fragment length polymorphism
      based method. Survival was assessed by Kaplan-Meier method and Cox regression
      analysis according to the XRCC1 genotypes in specified adjuvant treatment groups.
      RESULTS: The rs25487 variant AA genotype was associated with worse breast cancer
      specific and overall survival in 238 patients receiving postoperative
      radiotherapy (p=0.031 and p=0.030, respectively). The AA genotype predicted worse
      breast cancer-specific survival among 75 patients treated with adjuvant
      chemotherapy (p=0.047). CONCLUSION: The XRCC1 rs25487 genotype may predict the
      outcome of postoperative radiotherapy and adjuvant chemotherapy in breast cancer.

PMID- 24922668
TI  - NF1 truncating mutations associated to aggressive clinical phenotype with
      elephantiasis neuromatosa and solid malignancies.
AB  - BACKGROUND/AIM: Von Recklinghausen disease is a syndrome characterized by a wide
      phenotypic variability giving rise to both, cutaneous and visceral benign and
      malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and
      plexiform neurofibromas. The latter can undergo malignant transformation and/or
      determine elephantiasis neuromatosa. Visceral tumors may include malignant
      peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas
      and abdominal neurofibromas. In the present study, the authors discuss the
      clinical and biomolecular characterization of a cohort of 20 families with a
      diagnosis of type 1 neurofibromatosis. PATIENTS AND METHODS: Clinically, the
      cohort includes three probands with elephantiasis neuromatosa and a peculiarly
      high incidence of breast and gastrointestinal cancer. RESULTS: Among the 14 NF1
      mutations documented, 10 encoding for a truncated protein have been associated to
      particularly aggressive clinical phenotypes including elephantiasis neuromatosa,
      malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal
      tumors. CONCLUSION: This effect on protein synthesis, rather than the type of NF1
      mutation, is the key to the explanation of the genotype-phenotype correlations in
      the context of neurofibromatosis type 1.

PMID- 24922670
TI  - Clinical efficacy of non-transplant therapies in patients with hepatocellular
      carcinoma with Child-Pugh C liver cirrhosis.
AB  - AIM: To compare clinical outcome in patients with Child-Pugh C hepatocellular
      carcinoma (HCC) treated with non-transplant therapies and those treated with best
      supportive care. PATIENTS AND METHODS: A total of 182 patients with HCC with
      Child-Pugh C cirrhosis were analyzed. Patients were classified into two groups:
      patients treated with non-transplant therapies (n=113, treated group) and
      untreated patients (n=69, untreated group). Furthermore, for reducing the bias in
      patient selection, a propensity score matching analysis was performed (55 pairs).
      RESULTS: The median survival time in the treated group was significantly longer
      than that in the untreated group (1.16 years vs. 0.21 years, p<0.001). After
      propensity score matching, the median survival time in the treated group remained
      significantly longer than that in the untreated group (0.95 years vs. 0.17 years,
      p=0.01). CONCLUSION: In patients with HCC with Child-Pugh C cirrhosis, those
      treated with non-transplant therapies might have longer survival than untreated
      patients.

PMID- 24922671
TI  - Clinical trial of a 7-peptide cocktail vaccine with oral chemotherapy for
      patients with metastatic colorectal cancer.
AB  - AIM: The combination of a peptide vaccine and tegafur-uracil plus leucovorin
      (UFT/LV) were evaluated in patients with metastatic colorectal cancer refractory
      to standard chemotherapy. PATIENTS AND METHODS: Thirty human leukocyte antigen
      (HLA)-A2402-positive patients were enrolled in the study. In a cycle of
      treatment, a vaccine comprising of seven synthetic peptides (five tumor antigen
      derived and two vascular endothelial growth factor receptor-derived) was injected
      weekly, and oral chemotherapy, UFT/LV was given daily for four weeks followed by
      one week of rest. The immunological and clinical responses were evaluated at the
      end of every five weeks. RESULTS: Notable adverse events included grade 1
      injection site redness/induration in 25 patients. Tumor imaging showed partial
      response in three patients, stable disease in 15, and progressive disease in 12.
      Survival analysis indicated that patients who exhibited positive cytotoxic T
      lymphocyte responses to all seven peptides had longer overall survival compared
      to other patients. CONCLUSION: A 7-peptide vaccine used with UFT/LV is safe and
      is recommended for further trials in patients with metastatic colorectal cancer.

PMID- 24922672
TI  - Prognostic significance of urine N1, N12-diacetylspermine in patients with non
      small cell lung cancer.
AB  - BACKGROUND: Recently N(1),N(12)-diacetylspermine, a diacetylated polyamine
      derivative, was recognized as a tumor marker in patients with several kinds of
      cancers. However, the significance of its levels in urine as a prognostic factor
      has not been elucidated. In the present study, we examined whether the urine
      N(1),N(12)-diacetylspermine levels can be used as a prognostic factor in patients
      with NSCLC. PATIENTS AND METHODS: Urine samples from 251 patients with NSCLC were
      collected prior to surgery and the urinary N(1),N(12)-diacetylspermine
      concentration was measured. Thereafter, all 251 patients underwent curative
      surgery and the analysis of prognosis was performed for over 10 years. Out of the
      251 patients, 91 had recurrent disease. The significance of the urinary
      N(1),N(12)-diacetylspermine level as a prognostic factor among all 251 patients
      and among the 91 patients with recurrence was evaluated. RESULTS: Univariate
      analysis of all 251 patients showed that the level of urinary N(1),N(12)
      diacetylspermine was a significant prognostic factor for disease-free survival
      and overall survival; however, multivariate analysis showed it had no
      significance. Conversely, the univariate and multivariate analyses of post
      recurrent survival of the 91 patients with recurrence showed that urinary
      N(1),N(12)-diacetylspermine was an independent prognostic factor for post
      recurrent survival. CONCLUSION: Patients with recurrence with positive urinary
      N(1),N(12)-diacetylspermine should undergo more intensive care and determination
      of urinary N(1),N(12)-diacetylspermine may contribute to improvement of prognosis
      of NSCLC.

PMID- 24922673
TI  - Cell-adhesion molecule expression and the proliferation of malignant
      mesothelioma: a post-mortem examination.
AB  - AIM: In order to determine if metastatic malignant mesothelioma cells are more
      aggressive than primary malignant mesothelioma cells, an analysis of the
      expression of the adhesion molecules E-cadherin and beta-catenin, concomitant
      with an assessment of the proliferative activity at primary and metastatic sites,
      was conducted in post-mortem samples. MATERIALS AND METHODS: E-cadherin or beta
      catenin expression was graded according to the percentage of positively-stained
      tumor cells. The proliferative activity was quantified by the Ki-67 labeling
      index. RESULTS: Histologically, the majority of metastatic tumors matched the
      primary tumor. In the epithelioid component of primary tumors, E-cadherin and
      beta-catenin expression ranged from 1+ to 4+. CONCLUSION: Malignant mesothelioma
      cells acquire a higher proliferative potential after metastasis, without any
      significant changes in their histology, although metastasis produces no definite
      trend on the expression of E-cadherin or beta-catenin.

PMID- 24922674
TI  - Long-term follow-up of intermediate-risk non-muscle invasive bladder cancer sub
      classified by multi-coloured FISH.
AB  - AIM: To examine the long-term follow-up of patients with that previously
      underwent risk stratification based on multicolour FISH testing. PATIENTS AND
      METHODS: On 81 patients with intermediate-risk urothelial carcinoma, a
      multicolour-FISH was performed. Patients were sub-divided into low- and high-risk
      groups based on chromosomal patterns. Univariate analysis, using Mantel-Cox log
      rank test for disease-free, progression-free survival and overall survival, was
      employed to determine the prognostic significance of FISH analysis. Survival
      times were calculated according to the Kaplan-Meier product-limit method and
      multivariate analysis using Cox proportional hazards regression model. RESULTS:
      The univariate Mantel-Cox log-rank test showed significant differences between
      the low-risk and the high-risk group for disease-free survival (p=0.005) and
      overall survival (p=0.038), but not for progression-free survival (p=0.129).
      CONCLUSION: Our long-term follow-up data appear to be able to divide tumors into
      low and high risk groups for recurrence based on molecular/genetic changes
      observed with FISH.

PMID- 24922675
TI  - Atypical lipomatous tumor with structural rearrangements involving chromosomes 3
      and 8.
AB  - Atypical lipomatous tumor (ALT) is an intermediate (locally aggressive)
      mesenchymal neoplasm with the potential to dedifferentiate to higher grades over
      time. It is cytogenetically characterized by the presence of one or more
      supernumerary ring and giant marker chromosomes. These abnormal chromosomes
      invariably contain amplified sequences derived from the 12q14-15 region. We
      describe a unique cytogenetic finding of ALT arising in the right lower back of a
      42-year-old man. Magnetic resonance imaging demonstrated a predominantly fatty
      mass with irregularly thickened, linear, swirled, and nodular septa. Contrast
      enhanced fat-suppressed T1-weighted images showed significant enhancement of the
      non-adipose areas. A sub-extensive resection was performed. Histologically, the
      tumor consisted predominantly of mature fat cells with atypical stromal cells and
      multivacuolated lipoblasts. Immunohistochemically, the tumor cells were positive
      for p16 (diffuse and strong signal) and cyclin-dependent kinase-4 (focal and weak
      signal) but negative for murine double-minute 2. Cytogenetic analysis displayed a
      t(3;8)(q28;q13) translocation as the sole anomaly or concomitant with a few other
      numerical and structural alterations. There has been no evidence of local
      recurrence two months after surgery. To the best of our knowledge, this is the
      first case of ALT with structural aberrations involving chromosomes 3 and 8,
      associated with an absence of 12q rearrangements. 

PMID- 24922676
TI  - Role of novel risk classification method, Prostate Cancer Risk Index (PRIX) for
      clinically localized prostate cancer after high-dose-rate interstitial
      brachytherapy as monotherapy.
AB  - AIM: To examine the role of the new grading system Prostate Cancer Risk Index
      (PRIX) with existing risk-grouping after high-dose-rate interstitial
      brachytherapy (HDR-ISBT) as monotherapy for localized prostate cancer. PATIENTS
      AND METHODS: We analyzed outcome in 100 patients treated by HDR-ISBT as
      monotherapy using PRIX and compared this with D'Amico, the National Comprehensive
      Cancer Network (NCCN), and Seattle classifications. The median follow-up was 74
      (range=48-109) months. RESULTS: Five-year prostate-specific antigen control and
      overall survival rates were 94% and 98%, respectively. PRIX separated the risks
      statistically significantly (p=0.004), while D'Amico (p=0.319), NCCN 2002
      (p=0.126), NCCN 2012 (p=0.052) and Seattle (p=0.112) classifications failed to
      show a statistically significant separation. CONCLUSION: PRIX is a more useful
      risk classification system in high-risk patient selection than existing risk
      classification system in clinically localized prostate cancer after HDR-ISBT as
      monotherapy.

PMID- 24922677
TI  - Detection of circulating tumor cells in colorectal and gastric cancer using a
      multiplex PCR assay.
AB  - AIM: The aim of this study was the development of a multiplex-PCR assay for the
      detection of circulating tumor cells in patients with colorectal and gastric
      cancer. PATIENTS AND METHODS: Peripheral blood samples were collected from 81
      patients with colorectal cancer, 16 with gastric cancer and 38 healthy blood
      donors, as controls. The samples were processed for RNA extraction and cDNA
      synthesis and were subsequently analyzed for the expression of cytokeratin 19
      (CK19), cytokeratin 20(CK20) and epidermal growth factor receptor (EGFR) with
      multiplex PCR. RESULTS: Statistical analysis revealed that the combination of
      CK19 and CK20 could be useful in the exclusion of colorectal cancer, as well as
      the diagnosis and exclusion of gastric cancer. Furthermore, the expression of
      EGFR was correlated with the presence of systemic disease in patients with
      colorectal cancer. CONCLUSION: Multiplex-PCR-based detection of circulating tumor
      cells could serve as a useful tool for the diagnosis, and monitoring of patients
      with colorectal and gastric cancer.

PMID- 24922678
TI  - How to improve the outcome in patients with AJCC stage I hepatocellular
      carcinoma.
AB  - AIM: Survival of patients with stage I hepatocellular carcinoma (HCC) is higher
      than in patients with more advanced disease, however many of them will ultimately
      die of tumor recurrence and liver failure. Our objective focuses on identifying
      the pathological and clinical factors that could affect disease-free (DFS) and
      overall survival (OS). In addition we reviewed the treatment offered for
      recurrence and its impact on OS. PATIENTS AND METHODS: Between January 1992 and
      December 2002, a total of 473 patients who underwent hepatectomy for HCC at the
      Kaohsiung Chang Gung Memorial Hospital were enrolled in this study. Relevant
      clinicopathological and perioperative variables were subjected to univariate and
      multivariate analysis. RESULTS: A total of 224 patients with a mean follow-up
      period of 4.6 years were analyzed. The 1-, 3-, 5-, and 10-year DFS rates were
      82.5%, 57.6%, 46.9% and 32.0% respectively. The 1-, 3-, 5-, and 10-year OS rates
      were 91.5%, 83.0%, 70.1% and 56.3% respectively. The multivariate analysis
      identified age >50 years, Indocyanine Green (ICG) clearance test and cirrhosis as
      independent factors that negatively impact DFS and age >= 50 years, resection
      type, presence of complications and tumor recurrence as factors affecting OS. In
      patients with recurrence (n=130), the factors that negatively impact OS were
      blood transfusion, age >= 50, blood loss and presence of surgical complications.
      CONCLUSION: Meticulous surgical technique is the key to improving the outcome of
      patients with stage I HCC. The presence of complications was the only modifiable
      clinicopathological factor that affected the OS in our study.

PMID- 24922679
TI  - Synovial sarcoma in knee joint, mimicking low-grade sarcoma confirmed by
      molecular detection of SYT gene split.
AB  - A 10-year-old boy underwent arthroscopic curettage for an intra-articular mass in
      knee joint. The tumor was diagnosed as low-grade fibrous sarcoma. Five years
      later, the patient presented with a recurrent tumor. The patient underwent a
      marginal excision with knee joint preservation and without adjuvant therapy. Two
      years after the last surgery, the patient is thriving with no evidence of
      recurrent or metastatic disease. The final diagnosis was synovial sarcoma
      confirmed via a SYT gene split performed with fluorescent in situ hybridization
      (FISH), although the tumor appeared as a low-grade fibrous type in a hematoxylin
      eosin section. The first curetted specimen was also confirmed to bear a SYT gene
      split. Synovial sarcoma has been conventionally recognized as a high-grade
      sarcoma. Our patient had a tumor that exhibited the characteristics of both a
      histologically and clinically low-grade tumor. From the present case, we consider
      that low-grade variants of synovial sarcoma do exist although their existence
      remains controversial. 

PMID- 24922680
TI  - Intratumoral but not peritumoral lymphatic vessel density measured by D2-40
      expression predicts poor outcome in gastric cancer--ROC curve analysis to find
      cut-off point.
AB  - BACKGROUND: Neolymphangiogenesis, a process of lymphatic vessel development in
      neoplastic tissue, may be a key event in the transmission of cancer cells into
      lymph nodes. The current study examined the relationship between lymphatic vessel
      density (LVD) measured by podoplanin (D2-40) expression, clinicopathological
      parameters and patient survival in gastric cancer. MATERIALS AND METHODS: D2-40
      expression was examined by immunohistochemistry in formalin-fixed paraffin
      embedded tissue specimens obtained from 60 patients with gastric cancer. D2-40
      immunoreactivity was analyzed in intratumoral and peritumoral compartments of
      tumors and correlated with tumor grade, type in Lauren's classification, lymph
      node status, distant metastasis, presence of ulceration, inflammatory
      infiltration, angio-invasion, lymphangio-invasion and patient survival using a
      Receiver Operating Characteristic (ROC) curve analysis to find cut-off points
      that enabled fair decision making in survival analysis. RESULTS: The mean values
      of intratumoral and peritumoral LVD were 6.63 and 11.25, respectively. Enhanced
      intratumoral LVD measured by D2-40 immunoexpression was correlated with the
      presence of lymph node metastases (p=0.04). Our study revealed a statistically
      significant correlation between intratumoral LVD measured by D2-40 expression and
      survival of patients with gastric cancer: an intratumoral LVD higher than 4.68 is
      significantly correlated with unfavorable prognosis, with a probability of death
      of approximately 80%. No significant relationship was identified between
      peritumoral LVD, lymph node status and survival in patients with gastric cancer.
      CONCLUSION: A high intratumoral LVD measured by D2-40 expression in specimens
      from primary tumors is strongly associated with lymph node metastasis and
      predicts worse clinical outcome. Increased intratumoral D2-40 immunoreactivity is
      a putative predictor of aggressive gastric cancer behavior.

PMID- 24922681
TI  - Histological changes after radiation therapy in patients with lung cancer: a
      prospective study.
AB  - BACKGROUND: Radiotherapy for lung cancer may induce pneumonitis. However,
      histological effects of radiotherapy on normal lung tissue are unknown.
      Transbronchial biopsy (TBB) is safe and accurate in monitoring parenchymal
      lesions in lung-transplanted patients. The aim of this prospective study was to
      evaluate whether histological changes of the healthy lung parenchyma after
      radiotherapy are present on TBB biopsies. PATIENTS AND METHODS: Twelve patients
      with lung cancer necessitating radiation therapy participated in the study.
      Serial TBBs were obtained from lung parenchyma contra-lateral to the tumor
      before, just after radiotherapy, and at six months post-irradiation. Evaluation
      of each specimen was based on the presence of congestion, inflammation,
      hemorrhage and fibrosis. RESULTS: A significant increase of interstitial fibrosis
      (thickness) and congestion was observed between the point prior to radiotherapy
      and after completion of radiotherapy (p=0.047), as well as between the pre
      radiotherapy point and at six months after radiotherapy (p=0.014). Six patients
      (50%) showed intra-alveolar fibroblastic growth after radiotherapy. No patient
      showed clinical or radiographic findings of radiation pneumonitis. CONCLUSION:
      Even in the absence of clinical or radiographic findings, the lung parenchyma
      contra-lateral to the tumor suffers early histological lesions after radiation
      therapy, as monitored by serial TBBs.

PMID- 24922682
TI  - Gemcitabine-based adjuvant chemotherapy for patients with advanced gallbladder
      cancer.
AB  - AIM: We investigated effects of gemcitabine-based adjuvant chemotherapy (GEM) on
      prognosis of patients with gallbladder cancer. PATIENTS AND METHODS: We
      retrospectively analyzed outcomes of 36 patients who underwent radical resection
      for gallbladder cancer from 2001 through to 2012, using chi(2) for prognostic
      factors and Kaplan-Meier estimator and log-rank tests for survival data. RESULTS:
      The GEM group had higher rates of lymph node positivity and distant metastasis,
      higher UICC stage and fewer R0 resections; their 5-year survival rate (60%) did
      not significantly differ from that of the controls (70.0%), nor was GEM a
      significant prognostic factor in univariate analysis. However, among patients who
      underwent R1 and R2 resections, GEM significantly improved prognosis in both
      univariate and multivariate analyses. Median survival of the R1/2 GEM group (66.4
      months) was significantly better than that of controls (5.4 months) (p=0.002).
      CONCLUSION: GEM improved prognosis of patients with gallbladder cancer after
      R1/R2 resections.

PMID- 24922683
TI  - Glasgow prognostic score is a useful predictive factor of outcome after
      palliative gastrectomy for stage IV gastric cancer.
AB  - BACKGROUND/AIM: The Glasgow prognostic score (GPS) is a predictor of outcome for
      several cancer types. The present study examined the significance of modified GPS
      (mGPS) in the prognosis of patients undergoing palliative surgery for stage IV
      gastric cancer. PATIENTS AND METHODS: A total of 42 patients with stage IV
      gastric cancer treated with palliative gastrectomy and gastrojejunostomy were
      included in the study. Univariate and multivariate analyses were performed to
      evaluate the relationship between clinicopathological factors and cancer-specific
      survival (CS). RESULTS: Among patients who underwent palliative surgery including
      gastrectomy and gastrojejunostomy, univariate analysis of CS identified the
      following significant risk factors: surgical treatment, chemotherapy and mGPS,
      and multivariate analysis revealed that mGPS was independently-associated with
      CS. In particular, among patients who underwent palliative gastrectomy, mGPS was
      shown to be the strongest independent predictive factor for CS. CONCLUSION: The
      mGPS was an independent predictive factor for survival in patients who underwent
      palliative surgery for stage IV incurable gastric cancer, especially for those
      who underwent palliative gastrectomy.

PMID- 24922684
TI  - Prognostic significance of pre- and postoperative glasgow prognostic score for
      patients with non-small cell lung cancer.
AB  - BACKGROUND: Our previous study showed the prognostic impact of preoperative
      Glasgow prognostic score (GPS) in patients who underwent resection for non-small
      cell lung cancer (NSCLC). In the present study, the relationship between
      postoperative GPS and prognosis was also examined in patients with NSCLC with
      preoperative GPS 1 or 2. PATIENTS AND METHODS: Three hundred and twelve
      consecutive patients resected for NSCLC with a follow-up period of more than five
      years were enrolled. The GPS was calculated as follows: patients with elevated C
      reactive protein level (>1.0 mg/dl) and hypoalbuminemia (<3.5 g/dl) were assigned
      to GPS 2. Patients with one or no abnormal value were assigned to GPS 1 or GPS 0.
      RESULTS: Study patients were allocated as follows: 264 (84.62%) to GPS 0; 31
      (9.94%) to GPS 1; and 17 (5.45%) to GPS 2. The prognosis of the patients with
      preoperative GPS 2 was significantly poorer. Postoperative GPS was also examined
      for 48 patients with preoperative GPS 1 or 2. In 30/48 patients, postoperative
      GPS was improved to GPS 0, however, the postoperative GPS of the remaining 18
      patients did not change to GPS 0. The 5-year survival of patients with
      postoperative GPS 0 and 1-2 were 73.02% and 11.11%, respectively. CONCLUSION:
      Preoperative GPS may be useful for postoperative prognosis of patients with
      NSCLC. Furthermore, persistently high GPS after surgery indicates poor prognosis
      in patients with NSCLC.

PMID- 24922685
TI  - Effect of long interval between hyperthermochemoradiation therapy and surgery for
      rectal cancer on apoptosis, proliferation and tumor response.
AB  - Neoadjuvant chemoradiotherapy is commonly used to improve the local control and
      resectability of locally advanced rectal cancer, with surgery performed after an
      interval of a number of weeks. We have been conducting a clinical trial of
      preoperative chemoradiotherapy in combination with regional hyperthermia
      (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In
      the current study we assessed the effect of a longer (>10 weeks) interval after
      neoadjuvant HCRT on pathological response, oncological outcome and especially on
      apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty
      eight patients with proven rectal adenocarcinoma who underwent HCRT followed by
      surgery were identified for inclusion in this study. Patients were divided into
      two groups according to the interval between HCRT and surgery, <= 10 weeks (short
      interval group) and >10 weeks (long-interval group). Patients in the long
      interval group had a significantly higher rate of pathological complete response
      (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of
      the long-interval group had a significantly higher rate of down-staging of T
      stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs.
      36.0%) than patients of the short-interval group. Furthermore, apoptosis in the
      long-interval group was relatively higher compared to that of the short-interval
      group, without a significant difference in the Ki-67 proliferative index and
      expression of p53 in the primary tumor. In conclusion, we demonstrated that a
      longer interval after HCRT (>10 weeks) seemed to result in a better chance of a
      pCR, a result confirmed by the trends in tumor response markers, including
      apoptosis, proliferation and p53 expression.

PMID- 24922686
TI  - Vascular invasion, but not lymphatic invasion, of the primary tumor is a strong
      prognostic factor in patients with colorectal cancer.
AB  - BACKGROUND: We previously showed that the presence of vascular invasion, but not
      lymphatic invasion, was a strong prognostic factor for breast cancer. Lymphatic
      invasion may represent mainly the selective affinity of cancer cells for lymph
      nodes. The present study was undertaken to evaluate the presence of vascular
      invasion that may reflect systemic disease as a predictor of disease recurrence
      in colorectal cancer, separate from lymphatic invasion of the primary tumor.
      PATIENTS AND METHODS: We retrospectively evaluated the cases of 177 consecutive
      patients with primary colorectal cancer who underwent colorectal resection. We
      examined the relationship between recurrence and the prognostic significance of
      clinicopathological factors, particularly lymphatic and vascular invasion.
      RESULTS: The presence of vascular invasion (v) was significant, while that of
      lymphatic invasion (ly) was not significant in univariate analysis. The presence
      of vascular invasion was an independent prognostic factor in multivariate
      analysis. Among the 60 patients in the ly-/v- group, one (1.7%) had disease
      recurrence, and among the 33 patients in the ly+/v- group, one (3.0%) had disease
      recurrence. On the other hand, among the 71 patients in the ly+/v+ group, 16
      patients (22.5%) suffered recurrence, and among the 13 patients in the ly-/v+
      group, four (30.8%) suffered recurrence. It is interesting to note that despite
      the presence of lymphatic invasion, the group without vascular invasion (ly+/v-)
      had a few patients with distant metastases, a result which is similar to that of
      the ly-/v- group. CONCLUSION: The presence of vascular invasion, but not
      lymphatic invasion, could be an indicator of high biological aggressiveness and
      may be a strong prognostic factor for colorectal cancer.

PMID- 24922687
TI  - Excellent prognosis of lepidic-predominant lung adenocarcinoma: low incidence of
      lymphatic vessel invasion as a key factor.
AB  - AIM: To clarify the prognostic value of predominant histological subtypes for
      small-sized lung adenocarcinoma. MATERIALS AND METHODS: Sixty-four specimens of
      resected invasive lung adenocarcinoma less than 20 mm in diameter with no lymph
      node metastasis were studied. These specimens were microscopically classified
      into predominant histological subtypes (21 lepidic, 16 acinar, 24 papillary, and
      three solid) according to the International association for the study of lung
      cancer/American thoracic society/European respiratory society adenocarcinoma
      classification. The relationships between tumor relapse and predominant
      histological subtypes were statistically analyzed. In addition the relationships
      between several pathological factors and predominant histological subtypes were
      statistically assessed. RESULTS: Kaplan-Meier relapse-free curves showed a five
      year relapse-free rate of 100% in 64 patients with lepidic-predominant
      adenocarcinoma, compared with a rate of 73.7% (p=0.035 by log rank test) in
      patients with non-lepidic-predominant adenocarcinoma (papillary, acinar, and
      solid). The only statistically significant pathological factor between lepidic
      predominant and non-lepidic-predominant histological subtypes was lymphatic
      vessel invasion as assessed by logistic regression analysis. CONCLUSION: In small
      sized lung adenocarcinoma, lepidic-predominant histological subtype is the best
      prognostic factor, and a low incidence of lymphatic vessel invasion in the
      histological subtype is a key factor for an excellent prognosis.

PMID- 24922688
TI  - Histological growth pattern of and alpha-actinin-4 expression in thyroid cancer.
AB  - AIM: To assess the clinicopathological significance of the histological growth
      pattern (HGP) and alpha-actinin-4 (ACTN4) expression in thyroid cancer. PATIENTS
      AND METHODS: We classified 83 thyroid cancer cases into infiltrative margin (IM)
      and pushing margin (PM) groups according to peripheral tumor margin contour and
      immunohistochemically determined ACTN4 expression. Correlations between clinical
      stage and clinicopathological characteristics were analyzed. RESULTS: IM and high
      ACTN4 expression were observed in 39% and 49% of cancer cases, respectively.
      Higher clinical stage was significantly correlated with older age, higher T and N
      factor, preoperative recurrent laryngeal nerve paralysis (pre-RLNP), IM, and poor
      prognosis. Patients with stage IV disease had significantly poorer prognosis than
      those with stages I-III. On multivariate analysis, older age, pre-RLNP, and IM
      correlated with higher clinical stages. IM was significantly correlated with high
      ACTN4 expression. CONCLUSION: IM, pre-RLNP, and ACTN4 expression could be novel
      indicators of tumor aggression and prognostic factors of thyroid cancer.

PMID- 24922689
TI  - Utility of measuring circulating tumor cell counts to assess the efficacy of
      treatment for carcinomas of unknown primary origin.
AB  - BACKGROUND/AIM: Carcinomas of unknown primary origin (CUPs) account for 3%-5% of
      all malignancies. The majority of CUPs have unfavorable prognosis and are
      chemoresistant. Predictive biomarkers should be established to improve
      therapeutic outcomes. Metastatic ability of CUPs may be related to the existence
      of circulating tumor cells (CTCs). PATIENTS AND METHODS: Ten patients diagnosed
      with CUP visiting the Akita University Hospital participated in this study. CTCs
      were calculated by the CellSearch system. RESULTS: The present observational
      study indicates that CTCs were detected in 50% of CUPs, and in 80%
      chemotherapeutically-naive cases. Furthermore, decrease in CTC count between the
      pre-treatment and post-treatment phases were observed in chemosensitive cases.
      CONCLUSION: Rapid assessment of the efficacy of chemotherapy by CTC count may
      become a useful predictive biomarker of CUPs.

PMID- 24922690
TI  - Short-term clinical outcomes of postoperative intrapelvic bleeding after extended
      pelvic surgery: a single institute experience.
AB  - BACKGROUND/AIM: Intrapelvic bleeding after extended pelvic surgery is fatal, but
      few reports have addressed this serious situation. The objective of the present
      study was to evaluate the short-term clinical outcome of this complication.
      PATIENTS AND METHODS: This study was a retrospective medical chart review of 130
      patients who underwent extended pelvic surgery between 2000 and 2012 at our
      Institute. Based on the classification of the bleeding pelvic artery, how initial
      hemostasis and control of secondary pelvic abscess were mainly evaluated.
      RESULTS: In 6 patients, bleeding involved a peripheral artery (peripheral group)
      and 4 a main artery (central group). For initial hemostasis, interventional
      radiology was efficacious. Compared to the peripheral group, even if initial
      hemostasis succeeded, unsatisfactory abscess drainage easily became fatal in the
      central group. CONCLUSION: Aggressive surgical abscess drainage should be
      considered at an appropriate time for optimal survival in patients with
      involvement of a main artery with insufficient tube drainage.

PMID- 24922691
TI  - Hypothyroidism as a predictive clinical marker of better treatment response to
      sunitinib therapy.
AB  - BACKGROUND: Tyrosine kinase inhibitors are standard treatment in patients with
      metastatic renal cell carcinoma (mRCC). Several studies have indicated that side
      effects including hypothyroidism may serve as potential predictive biomarkers of
      treatment efficacy. PATIENTS AND METHODS: All patients with clear cell mRCC
      treated with sunitinib in the first-line setting in our Center between November
      2008 and October 2013 were included. Thyroid function was assessed after every 2
      cycles. Prognostic factors were tested using Cox proportional hazards model for
      univariate analysis. RESULTS: During treatment, 29.3% developed hypothyroidism,
      with a median of peak TSH values of 34.4 mIU/L. Patients who had both TSH >4
      mIU/L and were receiving substitution therapy with levothyroxine had prolonged
      PFS compared to all other patients (25.3 months vs. 9.0 months; p=0.042).
      CONCLUSION: The rate of hypothyroidism as a side-effect of sunitinib in patients
      with mRCC is significant. Patients with symptomatic hypothyroidism experienced
      significantly longer PFS, but without difference in OS.

PMID- 24922692
TI  - Gefitinib and afatinib treatment in an advanced non-small cell lung cancer
      (NSCLC) patient undergoing hemodialysis.
AB  - Renal failure in cancer patients is not a rare clinical condition and often
      contraindicates anticancer drug treatment; moreover, chemotherapeutic drugs are
      frequently identified as possible iatrogenic cause of renal failure. Molecular
      therapies, when appropriate, could represent a therapeutic option for cancer
      patients with severe renal disease, but the lack of knowledge in this field, at
      present, limits their use in patients undergoing dialysis. Herein we describe a
      case, at our knowledge the first reported, of a patient with advanced lung
      adenocarcinoma on maintenance hemodialysis treated with gefitinib and then with
      afatinib; we also reviewed the literature on epidermal growth factor receptor
      (EGFR) tyrosine-kinase inhibitors (TKIs) used in NSCLC patients with concomitant
      renal impairment. 

PMID- 24922693
TI  - Relationship between EGFR mutations and clinicopathological features of lung
      adenocarcinomas diagnosed via small biopsies.
AB  - AIM: We performed this study to evaluate the frequency of epidermal growth factor
      receptor (EGFR) mutations and their association with the histological subtype of
      lung adenocarcinoma diagnosed via small biopsy specimens. PATIENTS AND METHODS:
      Three hundred and fifty-nine lung adenocarcinoma specimens were tested for EGFR
      mutation by a direct sequencing method. In 135 patients, histological subtypes
      were classified according to the 2011 International Association for the Study of
      Lung Cancer/American Thoracic Society/European Respiratory Society
      classification. We compared the EGFR mutation frequency by clinicopathological
      characteristics. RESULTS: We detected 135 (37.6%) EGFR mutations and the
      incidence was highest in women who never smoked (54.6%). With regard to
      histological subtype, the highest prevalence of EGFR mutation was found in
      papillary (81.3%), followed by lepidic (70.4%), acinar (58.1%) and solid (28.3%)
      tumor types. In addition, the expression of thyroid transcription factor-1 was
      significantly higher in tumors with the EGFR mutation than in those without
      (p<0.001). CONCLUSION: The histological subtype of adenocarcinoma can be
      predictive of existing EGFR mutation, although the histology was confirmed using
      only small biopsies.

PMID- 24922694
TI  - The role of sentinel lymph node biopsy in patients with local recurrence or in
      transit metastasis of melanoma.
AB  - From January 2003 to March 2010, a prospective study was undertaken at the
      National Cancer Research Institute of Genoa in 15 patients with melanoma who had
      local recurrence (LR) or a few (<= 3) in-transit metastases and clinically
      negative regional lymph nodes with the aim of defining: i) the feasibility of
      sentinel node re-staging (r-sN) of the regional nodal basin; ii) the prognostic
      value of sentinel node status, and iii) the potential benefit in terms of disease
      free survival and overall survival in patients with an histologically-positive
      sentinel node undergoing therapeutic regional lymph node dissection. Preoperative
      lymphoscintigraphy was performed to identify the r-sN: the radiotracer was intra
      dermally injected around the LR or in-transit metastasis. Moreover, 10 min prior
      to the operative procedure, 0.5 ml intradermal injection of Patent-Blue-V dye was
      given around each LR or in-transit metastasis site, so that r-sN identification
      was achieved by both visualization of the nodal blue dye staining and the
      information supplied by gamma-detection probe. At least one sentinel node was
      intra-operatively identified in each patient, and a tumor-positive r-sN was
      required in four out of fifteen patients. The interval between the diagnosis of
      primary melanoma and the onset of recurrence was longer, although not
      significantly, in patients with tumor-negative r-sN, a compared to tumor-positive
      r-sN (49 +/- 47 months vs. 25 +/- 19 months, p=0.342). There was a trend toward
      an improved 1-, 3-, and 5-year disease-free survival and overall survival in
      patients with tumor-negative r-sN a compared to tumor-positive r-sN. Hence, the r
      sN proved to be a feasible and accurate staging procedure even in patients with a
      few localizations of LR or in-transit metastases (<= 3). r-sN identified those
      with a more favorable prognosis, supporting an aggressive therapeutic approach in
      the natural history of their disease; moreover, an unnecessary regional lymph
      node dissection was safely avoided in 11 out of 15 73.3% patients because they
      had a tumor-negative r-sN.

PMID- 24922696
TI  - Microsatellite instability analysis in uterine cavity washings to detect
      endometrial cancer in Lynch syndrome.
AB  - AIM: To assess the feasibility of Microsatellite Instability (MSI) analysis in
      uterine cavity washings for detecting endometrial cancer in Lynch syndrome.
      MATERIALS AND METHODS: This was a proof-of-concept study in Lynch syndrome
      patients, scheduled for hysterectomy. At the beginning of surgical procedure,
      uterine cavity washings were performed, and sent for MSI analysis. Pathological
      examination of the uterus was associated with mismatch repair protein expression
      and MSI analysis. RESULTS: Nine patients were included in the study. Uterine
      cavity washings were feasible and interpretable in all cases. Final histological
      report identified 2 endometrial cancers and 7 benign specimens. There was no
      atypical hyperplasia. Sensitivity, specificity, positive predictive value, and
      negative predictive value of MSI analysis in uterine washings reached 100% in all
      cases. Concordance of MSI presence or absence was absolute between uterine
      washings and final histology. CONCLUSION: MSI analysis in uterine cavity washings
      may be a promising screening tool for Lynch syndrome-associated endometrial
      cancer diagnosis.

PMID- 24922695
TI  - Predictive role of CEA and CYFRA 21-1 in patients with advanced-stage NSCLC
      treated with erlotinib.
AB  - BACKGROUND: Tumor biomarkers are used for predicting therapy effect and prognosis
      of patients with non-small cell lung cancer (NSCLC). We focused on their
      potential role in prediction of the efficacy of erlotinib. PATIENTS AND METHODS:
      In a total of 144 patients with advanced-stage (IIIB or IV) NSCLC treated with
      erlotinib, pre-treatment levels of soluble carcinoembryonic antigen (CEA) and
      cytokeratin markers in serum were measured. RESULTS: The median progression-free
      and overall survival for patients with a high level of carcinoembryonic antigen
      (CEA) was 1.9 and 8.6 vs. 2.9 and 16.1 months for patients with low CEA (p=0.046
      and p=0.116). The respective medians for patients with a high level of
      cytokeratin-19 fragment were 1.9 and 6.1 vs. 3.4 and 23.8 months for patients
      with the low cytokeratin-19 fragment (p<0.001 and p<0.001). CONCLUSION: High pre
      treatment serum levels of one or both biomarkers are associated with poor outcome
      of patients with NSCLC treated with erlotinib.

PMID- 24922697
TI  - NAT2, XRCC1 and hOGG1 polymorphisms, cigarette smoking, alcohol consumption and
      risk of upper aerodigestive tract cancer.
AB  - AIM: To evaluate associations between polymorphisms of the N-acetyltransferase 2
      (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross
      complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract
      (UADT) cancer. PATIENTS AND METHODS: A case-control study involving 117 cases and
      224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by
      automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were
      determined by Polymerase Chain Reaction followed by Restriction Fragment Length
      Polymorphism (PCR-RFLP) methods. RESULTS: Slow metabolization phenotype was
      significantly associated as a risk factor for the development of UADT cancer
      (p=0.038). Furthermore, haplotype of slow metabolization was also associated with
      UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC
      genotypes) was shown as a protective factor against UADT cancer in moderate
      smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes),
      in turn, was a protective factor against UADT cancer only among never-drinkers
      (p=0.048). CONCLUSION: Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1
      Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

PMID- 24922698
TI  - Impact of preoperative thrombocytosis on pathological outcomes and survival in
      patients treated with radical cystectomy for bladder carcinoma.
AB  - AIM: To investigate the impact of preoperative platelet count on pathological
      findings at the time of Radical Cystectomy for Bladder Cancer and postoperative
      cancer-specific and overall survival. PATIENTS AND METHODS: A total of 906
      consecutive patients treated with Radical Cystectomy for Bladder Cancer between
      1995 and 2012 at a tertiary referral Center were included in the study.
      Thrombocytosis was defined as >400,000 platelets/MUl, in agreement with the
      standard assumed by the central laboratory of our Institution. Univariable and
      multivariable logistic regression analyses were used to investigate the impact of
      preoperative platelet count on pathological stage. Univariate and multivariate
      Cox regression analyses were also adopted to predict both cancer-specific and
      overall survival. RESULTS: The mean age at cystectomy was 67.25 years. The mean
      and median platelet counts were 242,100/MUl and 227,500/MUl. At a mean follow-up
      time of 41 months, the 2- and 5-year cancer-specific and overall survival were
      found to be 83.1% and 75.2% and 68.3 and 59.8%, respectively. At Univariable
      analysis, thrombocytosis count was significantly associated with adverse
      pathological disease stage (p <= 0.007) and lymph node invasion (p=0.05).
      Platelet count was significantly associated to patient survival at univariable
      analysis (Hazard Ratio=1.76 and 1.39 for overall survival and cancer specific
      survival, respectively; all p<0.05). At multivariate Cox regression analysis,
      platelet count was documented to be significantly related only to overall
      survival (Hazard Ratio=64,1.03-2.81; p=0.05). CONCLUSION: Preoperative platelet
      count should be taken into account as a factor predictive of postoperative
      oncological outcomes after radical cystectomy for bladder cancer and patients
      should be counseled accordingly.

PMID- 24922746
TI  - Abstracts of the British Cardiovascular Society Annual Conference 2014, 02-04
      June 2014, Manchester, UK.

PMID- 24922745
TI  - Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer
      incidence and mortality: systematic review and meta-analysis of randomised
      controlled trials and observational studies.
AB  - OBJECTIVES: To review, summarise, and compare the evidence for effectiveness of
      screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal
      cancer occurrence and deaths. DESIGN: Systematic review and meta-analysis of
      randomised controlled trials and observational studies. DATA SOURCES: PubMed,
      Embase, and Web of Science. Two investigators independently extracted
      characteristics and results of identified studies and performed standardised
      quality ratings. ELIGIBILITY CRITERIA: Randomised controlled trials and
      observational studies in English on the impact of screening sigmoidoscopy and
      screening colonoscopy on colorectal cancer incidence and mortality in the general
      population at average risk. RESULTS: For screening sigmoidoscopy, four randomised
      controlled trials and 10 observational studies were identified that consistently
      found a major reduction in distal but not proximal colorectal cancer incidence
      and mortality. Summary estimates of reduction in distal colorectal cancer
      incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46%
      (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to
      79%) in per protocol analysis of randomised controlled trials, and 64% (50% to
      74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy,
      evidence was restricted to six observational studies, the results of which
      suggest tentatively an even stronger reduction in distal colorectal cancer
      incidence and mortality, along with a significant reduction in mortality from
      cancer of the proximal colon. Indirect comparisons of results of observational
      studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower
      risk of incident colorectal cancer and death from colorectal cancer after
      screening colonoscopy even though this incremental risk reduction was
      statistically significant for deaths from cancer of the proximal colon only.
      CONCLUSIONS: Compelling and consistent evidence from randomised controlled trials
      and observational studies suggests that screening sigmoidoscopy and screening
      colonoscopy prevent most deaths from distal colorectal cancer. Observational
      studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases
      mortality from cancer of the proximal colon. This added value should be examined
      in further research and weighed against the higher costs, discomfort,
      complication rates, capacities needed, and possible differences in compliance.

PMID- 24922977
TI  - The author responds.

PMID- 24922978
TI  - The author responds.

PMID- 24922979
TI  - Growth and variability in health plan premiums in the individual insurance market
      before the Affordable Care Act.
AB  - Before we can evaluate the impact of the Affordable Care Act on health insurance
      premiums in the individual market, it is critical to understand the pricing
      trends of these premiums before the implementation of the law. Using rates of
      increase in the individual insurance market collected from state regulators, this
      issue brief documents trends in premium growth in the pre-ACA period. From 2008
      to 2010, premiums grew by 10 percent or more per year. This growth was also
      highly variable across states, and even more variable across insurance plans
      within states. The study suggests that evaluating trends in premiums requires
      looking across a broad array of states and plans, and that policymakers must
      examine how present and future changes in premium rates compare with the more
      than 10 percent per year premium increases in the years preceding health reform.

PMID- 24922980
TI  - Current good manufacturing practices, quality control procedures, quality
      factors, notification requirements, and records and reports, for infant formula.
      Final rule.
AB  - The Food and Drug Administration (FDA or we) is issuing a final rule that adopts,
      with some modifications, the interim final rule (IFR) entitled "Current Good
      Manufacturing Practices, Quality Control Procedures, Quality Factors,
      Notification Requirements, and Records and Reports, for Infant Formula''
      (February 10, 2014). This final rule affirms the IFR's changes to FDA's
      regulations and provides additional modifications and clarifications. The final
      rule also responds to certain comments submitted in response to the request for
      comments in the IFR.

PMID- 24922981
TI  - Postmarketing safety reports for human drug and biological products; electronic
      submission requirements. Final rule.
AB  - The Food and Drug Administration (FDA or we) is amending its postmarketing safety
      reporting regulations for human drug and biological products to require that
      persons subject to mandatory reporting requirements submit safety reports in an
      electronic format that FDA can process, review, and archive. FDA is taking this
      action to improve the Agency's systems for collecting and analyzing postmarketing
      safety reports. The change will help the Agency to more rapidly review
      postmarketing safety reports, identify emerging safety problems, and disseminate
      safety information in support of FDA's public health mission. In addition, the
      amendments will be a key element in harmonizing FDA's postmarketing safety
      reporting regulations with international standards for the electronic submission
      of safety information.

PMID- 24922982
TI  - Final priority. National Institute on Disability and Rehabilitation Research-
      Rehabilitation Research and Training Centers. Final priority.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority for the Rehabilitation Research and Training Center (RRTC)
      Program administered by the National Institute on Disability and Rehabilitation
      Research (NIDRR). Specifically, we announce a priority for an RRTC on Health and
      Function of Individuals with Physical Disabilities. The Assistant Secretary may
      use this priority for competitions in fiscal year (FY) 2014 and later years. We
      take this action to focus research attention on an area of national need. We
      intend the priority to contribute to improved outcomes of health and function of
      individuals with physical disabilities.

PMID- 24922983
TI  - Obtaining evidence beyond the current "special arrangement sources." Interim
      final rule with request for comments.
AB  - We are amending our regulations to state that we will obtain evidence from any
      appropriate source. Our current regulations provide that we will obtain
      information from "special arrangement sources'' for those infrequent situations
      when we are in a better position than our State agency partners to obtain
      evidence. Due to improved evidence collection through our increased use of health
      information technology (health IT), we are obtaining evidence electronically with
      increasing frequency. We expect that, over time, the electronic exchange of
      medical records will become our primary means for obtaining medical evidence. As
      we increase our use of health IT, the designation of "special arrangement
      sources'' will no longer adequately describe from whom we collect evidence.

PMID- 24922984
TI  - The consequential validity of ABFM examinations.

PMID- 24922985
TI  - A self-guided relaxation module for telepsychiatric services: development,
      usefulness, and feasibility.
AB  - OBJECTIVE: A modified form of the standard autogenic relaxation exercise was
      developed as part of a telepsychiatry project, which aims to deliver mental
      healthcare to remote areas through the net, and through the agency of non
      specialists. This study describes the development and evaluation of a brief and
      simpler form of a relaxation technique, the Self-Guided Relaxation (SGR). METHOD:
      SGR is a systematic technique to focus on muscle groups and feel the heaviness
      and relaxation through suggestions to induce relaxation in the body. The SGR was
      taught to 37 patients with different psychiatric disorders over two sessions a
      week apart. Measures of change used were scores on the Hamilton Anxiety Rating
      Scale (HAM-A) and a visual analog scale. Its usefulness and feasibility was
      examined over a follow-up period of one month. Additionally a group of non
      specialists was trained in SGR supplemented by audiovisual aids and printed
      instructions. These therapists rated the ease in learning and administering SGR
      in patients. RESULTS: There was a consistent reduction in the HAM-A scores over
      the follow-up period among patients. Improvements were also noted in positive
      experiences, adherence, depth of relaxation achieved, perceived benefit, and
      patient satisfaction. Majority of the patients, relatives, and therapists
      reported that they could administer or practice SGR after having learned the
      technique in a single session lasting about 30 minutes. The use of audio-video
      aids and manual was helpful in making the process of learning easy. CONCLUSIONS:
      Preliminary findings of usefulness, feasibility, and acceptance of the SGR were
      encouraging. These findings pave way for larger, randomized controlled study and
      for testing applicability of the SGR as a net-based psychological intervention.

PMID- 24922986
TI  - An update on the efficacy of cognitive-behavioral therapy, cognitive therapy, and
      exposure therapy for posttraumatic stress disorder.
AB  - OBJECTIVE: Even though cognitive-behavioral therapy (CBT) is the current
      treatment of choice for posttraumatic stress disorder (PTSD), it is still unclear
      which components of its protocol are more important for clinical improvement.
      This study aims to replicate a previous review, updating findings on the efficacy
      of CBT, cognitive therapy (CT), and exposure therapy (ET) for PTSD when compared
      with other well-established treatments or conditions without active treatment.
      METHOD: The search was performed in the databases Cochrane, Embase, and Medline.
      Studies were required to be randomized controlled trials published between 2006
      and 2012 comparing CBT, CT, or ET with (1) each other, (2) other active
      treatments (e.g., EMDR, counseling, supportive therapy), or (3) assessment-only
      conditions. The main outcome measures were diagnostic and symptomatic remission.
      RESULTS: The final sample contained 29 articles. CBT, CT, and ET were shown to be
      efficacious treatments individually when compared to assessment-only conditions,
      with no difference found between treatments. Comparison with other active
      treatments favored ET. Both included studies comparing CBT and EMDR favored the
      latter. CONCLUSIONS: CBT and its components still appear to be equally
      efficacious in improving PTSD symptoms and diagnosis. Even so, a current tendency
      of researchers to focus on ET exists. EMDR shows interesting results compared to
      CBT. Further research should clarify the lasting effects, efficiency, and other
      comparative benefits of each protocol.

PMID- 24922987
TI  - The role of children with congenital anomalies in generating parental depressive
      symptoms.
AB  - BACKGROUND: Many expectant parents wish to have a normal child. Unfortunately
      this does not always happen and some of them may have a child with birth defects
      leading to detrimental psychological effects on the parents. One of the common
      presentations generally observed is depression. The presence of depressive
      symptoms amongst such parents needs to be recorded to find out its prevalence.
      The results of such finding can help shape future programs for the prevention and
      treatment in this population group. This study will therefore explore the extent
      of depressive symptoms amongst parents of children with congenital anomalies.
      METHODS: A case control study design was chosen. Ethical Review Board gave
      approval for the study on December 31, 2010, and the collection of data was
      started on January 5, 2011. Two randomly chosen samples of 132 parents each were
      collected from National Institute of Child Health (NICH), Ida Rieu, and Civil
      Hospital Karachi (CHK) over 8 months. First group consisted of parents of
      children with congenital anomalies and the second group was chosen as the control
      group from general population. Zung scale was used to record the presence of
      depressive symptoms in these two populations. Mann-Whitney test was performed to
      compare the depression scores. RESULTS: The scale was completed by 132 parents in
      both sets. The parents of children with congenital anomalies showed greater (p <
      0.0001) depressive symptoms. Mothers displayed greater (p = 0.029) depressive
      symptoms than fathers. CONCLUSION: The parents of children with anomalies (60.6%)
      had more depressive symptoms than parents of normal children (27.3%).

PMID- 24922988
TI  - Mental adjustment to cancer: the role of anxious and depressive symptoms under
      treatment.
AB  - OBJECTIVE: Depression is a risk factor for poor quality of life and mental
      adjustment to cancer. This research aims to evaluate the course of mental
      adjustment to illness of cancer patients with anxious-depressive symptoms who
      receive antidepressant therapy (ADT). METHOD: Eighty oncological patients with
      and without depressive symptoms were divided into three groups. Group 1: 30
      depressed cancer patients who underwent ADT with SSRI; Group 2: 30 depressed
      cancer patients who refused ADT; Group 3: 20 non-depressed cancer patients.
      Patients were evaluated at tO and 4 (tl) and 12 (t2) weeks later through:
      Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS),
      Hospital Anxiety Depression Scale (HADS), and MINI-MAC. RESULTS: HDRS and HARS
      mean scores were stable and under threshold across the study only in Group 3; at
      t2 they improved in Group 1 and worsened in Group 2. The improvements in anxiety
      and depression scores were associated with ADT and related to the changes in Mini
      MAC helpless-hopeless, anxious preoccupations, cognitive avoidance and fighting
      spirit dimensions. CONCLUSION: The improvement of mental adjustment to illness is
      directly related to the decrease of anxious-depressive symptoms among depressed
      cancer patients under antidepressant therapy.

PMID- 24922989
TI  - Diagnostic validity of the composite international diagnostic interview (CIDI)
      depression module in an East African population.
AB  - OBJECTIVE: To evaluate the validity and reliability of the structured Composite
      International Diagnostic Interview (CIDI) in diagnosing current major depressive
      disorder (MDD) among East African adults. METHODS: A sample of 926 patients
      attending a major referral hospital in Ethiopia participated in this diagnostic
      assessment study. We used a two-stage study design where participants were first
      interviewed using an Amharic version of the CIDI and a stratified random sample
      underwent a follow-up semi-structured clinical interview conducted by a
      psychiatrist, blinded to the screening results, using the Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN) instrument. We tested construct validity by
      examining the association of the CIDI and World Health Organization Quality of
      Life (WHO-QOL) questionnaire. We calculated the psychometric properties of the
      CIDI using the SCAN diagnostic interview as a gold standard. RESULTS: We found
      that the Amharic version of the CIDI diagnostic interview has good internal
      reliability (Cronbach's alpha = 0.97) among Ethiopian adults. Compared to the
      SCAN reference standard, the CIDI had fair specificity (72.2%) but low
      sensitivity (51.0%). Our study provided evidence for unidimensionality of core
      depression screening questions on the CIDI interview with good factor loadings on
      a major core depressive factor. CONCLUSION: The Amharic language version of the
      CIDI had fair specificity and low sensitivity in detecting MDD compared with
      psychiatrist administered SCAN diagnosis. Our findings are generally consistent
      with prior studies. Use of fully structured interviews such as the CIDI for MDD
      diagnosis in clinical settings might lead to under-detection of DSM-IV MDD.

PMID- 24922990
TI  - A young woman presenting with psychotic and mood symptoms from anti-N-methyl-D
      aspartate receptor (NMDA-R) encephalitis: an emerging diagnosis.
AB  - Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis, first characterized in
      2005, is a neurological disease with prominent psychiatric features that
      frequently involves the consultation of psychiatrists. Since its discovery, the
      rate of diagnosis of new cases has increased rapidly and several epidemiological
      studies now confirm that NMDA-R encephalitis may be as common as many other
      prominent infectious etiologies of encephalitis. We describe a case of a young
      woman presenting initially with psychotic and mood symptoms who was found to have
      anti-NMDA-R encephalitis. We further provide details of her treatment and
      prolonged recovery process after hospital discharge with a review of the
      literature and discussion of the epidemiology, symptomology, diagnosis, and
      management of both the neurologic and psychiatric manifestations of this
      condition. Last, we contextualize the importance of anti-NMDA-R encephalitis for
      psychiatrists, highlighting the role for psychiatrists in establishing the
      initial diagnosis as well as in providing ongoing psychiatric care.

PMID- 24922991
TI  - Improving the doctor-patient relationship in China: the role of balint groups.
AB  - OBJECTIVE: Doctor-patient relationships in China have been deteriorating for the
      past 10 years. Many Chinese doctors are involved in tense and conflictual doctor
      patient relationships. Most patients do not trust doctors or other medical staff
      and physical attacks on these professionals have become a common event. The
      Balint group offers a better understanding of the doctor-patient relationship in
      a safe environment and relieves the doctors from the daily stress. METHOD: This
      article (1) describes the specifics of Balint work in China, (2) reports
      experiences from the first International Balint Conference in China, and (3)
      compares these experiences with the doctor-patient relationship described by
      Michael and Enid Balint in the 1950s. RESULTS: Chinese doctors have a great need
      to communicate, to share their own feelings of powerlessness, helplessness,
      frustration, and anger. The Balint method is highly appreciated in China. All
      participants experienced the 2 1/2-day meeting as very helpful. Also, in China,
      Balint work as relationship work in the analytical group process fosters the
      ability for introspection alongside openness, unconscious processes, "thinking
      outside the box," "courage of one's own stupidity," and "beginner's spirit," thus
      promoting the individuation, the "small but significant change in the personality
      of the doctor." CONCLUSIONS: Perhaps Balint work in China is a contribution to
      the integration of traditional Chinese virtues: benevolence, tolerance,
      magnanimity, and prudence with modern medicine. Balint work could be an
      alternative to the outcome-oriented pressure to perform and to the machine
      paradigm of biomedicine.

PMID- 24922992
TI  - Shade determination using camouflaged visual shade guides and an electronic
      spectrophotometer.
AB  - The aim of the present study was to compare a camouflaged visual shade guide to a
      spectrophotometer designed for restorative dentistry. Two operators performed
      analyses of 66 subjects. One central upper incisor was measured four times by
      each operator; twice with a camouflaged visual shade guide and twice with a
      spectrophotometer Both methods had acceptable repeatability rates, but the
      electronic shade determination showed higher repeatability. In general, the
      electronically determined shades were darker than the visually determined shades.
      The use of a camouflaged visual shade guide seems to be an adequate method to
      reduce operator bias.

PMID- 24922993
TI  - The clinical features and their impact on the prosthodontic management in a case
      of Gardner's syndrome.
AB  - Gardner's syndrome is a variant of Familial Adenomatous Polyposis (FAP), a
      condition that manifests as hundreds of colorectal polyps likely to undergo
      malignant change by the fourth decade. Early diagnosis of this condition has the
      potential to be life saving for individuals and due to its inherited nature other
      family members can often also be affected. Additional features of Gardner's
      Syndrome include multiple jaw osteomas with missing teeth that can make
      prosthodontic treatment a challenge. This case report highlights the presenting
      features and the prosthodontic problems faced when treating a patient with
      Gardner's syndrome.

PMID- 24922994
TI  - The quality of impressions for crowns and bridges: an assessment of the work
      received at three commercial dental laboratories. assessing qualities of
      impressions that may lead to occlusal discrepancies with indirect restorations.
AB  - There are few published studies that directly assess the quality of impressions
      for crowns and bridges in the UK. This paper considers aspects of impression
      quality with particular attention to factors causing potential occlusal
      discrepancies in the final restoration. To this end three dental laboratories
      were visited over a 3-month period. All impressions for conventional crown and
      bridgework that arrived on the days of the visits were examined and assessed
      against criteria defined on a custom-designed assessment form. A total of 206
      impression cases were considered in this study. Flexible impression trays were
      used for 65% of working impressions. Their use was more common for NHS work than
      for private work. 31.9% of all alginate impressions examined were not adequately
      fixed to the tray. Visible contamination of impressions was not uncommon.

PMID- 24922995
TI  - Effect of saliva and blood contamination on the bi-axial flexural strength and
      setting time of two calcium-silicate based cements: Portland cement and
      biodentine.
AB  - This study evaluated the effect of contamination with saliva and blood on the bi
      axial flexural strength and setting time of pure gray Portland cement and
      Biodentine (Septodont, Allington, UK). A one-way ANOVA showed that contamination
      caused no significant difference between the cements in bi-axial flexural
      strength (P> 0.05). However there was a significant difference in setting time
      (P<O.001), with Portland cement taking longer than Biodentine, regardless of the
      contaminant, and contamination with blood increased the setting time of both
      materials. Biodentine was similar in strength to Portland cement, but had a
      shorter setting time for both contaminated and non-contaminated samples.

PMID- 24922996
TI  - Colour stability of denture teeth submitted to different cleaning protocols and
      accelerated artificial aging.
AB  - Acrylic resin is widely used for artificial teeth manufacturing due to several
      important characteristics; however, this material do not present acceptable
      colour stability over the course of time. This study evaluated the effect of
      different cleaning protocols and accelerated artificial aging on colour stability
      of denture teeth made of acrylic resin. Sixty denture teeth in dark and light
      shades were used, and separated according to the treatment to which they were
      submitted. Results demonstrated that colour stability of artificial teeth is
      influenced by the cleaning solution and artificial aging, being dark teeth more
      susceptible to colour alteration than lighter ones.

PMID- 24922997
TI  - Effect of chlorhexidine on bond strength between glass-fiber post and root canal
      dentine after six month of water storage.
AB  - Aim of this study was to assess the influence of chlorhexidine digluconate (CHX)
      application on bond strength of glass fibre reinforced composite (FRC) posts to
      root dentine using adhesive luting systems. Forty extracted human mandibular
      premolars were endodontically treated and root canals were prepared. Teeth were
      divided into 2 groups according to luting system as SuperBond C&B (etch-and
      rinse/chemical cure) and FuturaBond DC (self-etch/ dual cure). Each group was
      further divided in 2 subgroups (n=10) according to whether CHX was applied or
      not. Group Futura/CHX: FuturaBond DC + CHX; group Futura: FuturaBond DC; group
      Super/CHX: Super Bond C&B + CHX; group Super: SuperBond C&B + CHX. Mean and
      standard deviation (in parenthesis) values of bond strength in MPa were: group
      Futura/CHX: 8.86 (1.96), group Futura: 7.65 (1.01), group Super/CHX: 17.47(2.93),
      group Super: 12.41 (3.83). Bond strength values were affected by the type of
      luting agent and CHX irrigation (p=0.001, two-way ANOVA). There were
      statistically significant differences among the groups according to one-way ANOVA
      (p<0.001). Significant differences were observed in bond strength between groups
      Super/CHX and Super (p=0.023), between groups Futura/CHX and Super/CHX (p<0.001).
      Application of CHX before luting procedure with etch-and-rinse/chemical cure
      luting agent of glass FRC post improved long-term bond strength between glass FRC
      and root dentine.

PMID- 24922998
TI  - Dimensional stability ofautoclave sterilised addition cured impressions and
      trays.
AB  - The aim of this study was to investigate the dimensional accuracy of impressions
      following sterilisation by autoclaving. Dental impressions (75) were of a
      dentoform containing 6 reference points. The impressions were split into 5 groups
      of 15, each group used a different impression technique. Groups were divided into
      3 subgroups with 5 impressions as control, 5 for disinfection by Perform-ID and 5
      being autoclaved. Measurements were made using a travelling light microscope. A
      minimal significant dimensional difference (0.01<P<0.05) was observed when using
      the one-stage impression method. No significant dimensional differences were
      observed for all other groups (P>0.05). The trays and materials tested were
      suitable for the autoclave sterilisation.

PMID- 24922999
TI  - In vitro effects of different moisture level and curing method on microleakage of
      resin cements to pulp chamber dentine.
AB  - This study evaluated the microleakage of resin cements in the pulp chamber
      dentin. Fifty specimens of sound human molars were divided into five groups.
      Composite cores cemented using Clearfil SA Luting in the first group to a dried
      dentin and in the second group to a moistened dentin and then light-cured. In
      third and fourth groups, cement was placed on dried and moistened dentin and self
      cured respectively. In fifth group, composite cores were cemented by Panavia
      F2.0. After thermocycling, microleakage was evaluated using fluid filtration
      technique. The highest microleakage mean value was observed in the group with
      light-cured to a dry dentin. The mode of curing in contrast to moisture value had
      significant effect on microleakage. The microleakage of self- adhesive resin
      cement used in this study was lower in case of self cured than in case of light
      cured and was not related to the dentin surface moisture.

PMID- 24923000
TI  - "Pay squeeze tells nurses they are undervalued".

PMID- 24923001
TI  - Expert forum "no longer needed".

PMID- 24923002
TI  - Unions to discuss pay with hunt.

PMID- 24923003
TI  - "Focus on continuing fitness to practise, not revalidation".

PMID- 24923004
TI  - "Noticing good is as important as noticing bad, just not as popular".

PMID- 24923005
TI  - "Use nutrition and hydration week to tell everyone you care".

PMID- 24923006
TI  - Accurate assessment patient weigh.
AB  - Measuring patient weight is considered a routine assessment that is frequently
      delegated to unregistered staff. Yet patient weight is a fundamental part of
      nutrition assessment and may be used to calculate drug dosages and assess fluid
      balance. It is vital that staff carrying out this measurement are trained and
      have access to appropriate equipment that is regularly calibrated.

PMID- 24923007
TI  - Use of fluid thickener to reduce dysphagia risk.
AB  - Swallowing difficulties are common among care home residents, and increase their
      risks of a range of conditions. A care home provider evaluated the use of fluid
      thickeners to reduce these risks, and implemented an initiative to improve
      understanding of dysphagia among both care and catering staff. This included
      changing the thickeners used and ensuring there was some consistency with regard
      to the terminology used undertaking staff training. related to food textures, as
      well ashe Francis report (Francis, 2013) states people must have access to

PMID- 24923008
TI  - Recovery-focused practice in mental health.
AB  - This article aims to identify service users' and nurses' perspectives on recovery
      focused practice through themes in the literature. Common themes were hope,
      person-centred care and consideration of service users' perspective.
      Recommendations on how practice could be improved are suggested from these
      themes.

PMID- 24923009
TI  - Prevention and treatment of meningococcal disease.
AB  - Meningococcal disease is a leading cause of death in children and young people.
      Part 1 of this two-part series discussed its epidemiology, pathophysiology, signs
      and symptoms (Dowson, 2014). Part 2 reviews the diagnosis, management and
      prevention of this disease.

PMID- 24923010
TI  - 60 seconds with Charlene Roe.

PMID- 24923011
TI  - Better life with a rare disease.

PMID- 24923012
TI  - Make sure your care is hit, not miss.

PMID- 24923013
TI  - A gathering of expert minds.

PMID- 24923014
TI  - Crying out for change.

PMID- 24923015
TI  - Managing symptoms of IBS in children and teenagers.

PMID- 24923016
TI  - Danger on a plate.

PMID- 24923017
TI  - Mystery meals no more.
AB  - Nearly one-third of patients admitted to U.S. hospitals are malnourished.
      Nutrition in- and outside the hospital is a patient care priority.

PMID- 24923018
TI  - With a few months to go, are you ready for ICD-10?

PMID- 24923019
TI  - Treating addiction: 'she'll be dead by then!'.

PMID- 24923020
TI  - Safety first: a rare trio teams up to improve surgery.

PMID- 24923021
TI  - Power of two: competitors bulk up buying power.

PMID- 24923022
TI  - Let's talk: post-acute sector 'hungry' for help.

PMID- 24923023
TI  - Connecting the continuum: connecting clinicians and patients who are just 'a wall
      away'.

PMID- 24923024
TI  - Tweeting and texting during disasters.

PMID- 24923025
TI  - Marketability: necessity: the mother of innovation.

PMID- 24923026
TI  - Pressing pause: CMS slows RAC... for now.
AB  - The federal government plans some tweaks to the Medicare audit program. Hospital
      officials say it's a good first step, but want larger reforms.

PMID- 24923027
TI  - The great migration.

PMID- 24923028
TI  - Capital planning and the future.

PMID- 24923029
TI  - Hospitals put nutrition on the front burner.
AB  - About half of all inpatients go undiagnosed. Paying attention to what and how all
      patients eat improves outcomes and lowers costs.

PMID- 24923030
TI  - The hybrid OR.

PMID- 24923031
TI  - A strategy beyond survival.

PMID- 24923032
TI  - Transforming governance: leading in the era of reform.

PMID- 24923033
TI  - Snow Day? no way.

PMID- 24923034
TI  - [Conflicts of interests: a key question for doctors].

PMID- 24923035
TI  - [What is the role of tricyclics in psychiatry today?].

PMID- 24923036
TI  - [Varicella pneumonia].

PMID- 24923037
TI  - [When a physician may propose to a smoker to use electronic cigarettes?].

PMID- 24923038
TI  - [Treatment of hepatitis C: current status and perspectives].
AB  - The treatment of hepatitis C virus (HCV) infection has significantly improved
      these last two decades. For nearly 15 years, the association of pegylated
      interferon alfa and ribavirin (PR) has allowed a sustained virologic response
      (SVR), i.e., a viral cure of the infection, in 45% of genotype 1-infected
      patients, 65% of genotype 4-, 70% in genotype 3- and around 85% of genotype 2
      infected patients. A better understanding of the HCV life-cycle has led to the
      development of direct-acting antiviral drugs (DAAs) targeted against viral
      proteins (NS3/4A protease, NS5B polymerase with nucleos(t)idic and non
      nucleos(t)idic inhibitors, NS5A viral replication complex). The combination of
      first generation protease inhibitors with PR has showed a high antiviral
      efficiency (75% of SVR in genotypes 1) with substantial side effects for the
      first generation protease inhibitors, which have obtained approval to market in
      2011 (Telaprevir and Boceprevir) and recommandations of use in HCV mono-infected
      patients in 2012 and in HCV/HIV coinfected in 2013. Then, the combination of
      second generation protease inhibitors with PR has increased SVR rates from 75 to
      90%, while reducing treatment duration, side effects and number of pills. Next
      step is now interferon and ribavirin free combination of DAAs, about to become
      the standard of care in 2015. These excellent results in 'easy-to-treat' patients
      and in small population studies has now been confirmed in phase III studies and
      in 'difficult-to-treat' patients (treatment - especially protease inhibitors
      experienced patients, cirrhotic patients, liver and renal transplant patients,
      HIV co-infected patients, and subjects with polypharmacy, at increased risk of
      drug interaction).

PMID- 24923039
TI  - [The bibliography of the thesis in 10 lessons: # 5 sourcing and social
      bookmarking].

PMID- 24923040
TI  - [Hypoglycemia could increase the risk of arrhythmia in diabetics, explaining the
      increased cardiovascular mortality in the intensive control of blood glucose].

PMID- 24923041
TI  - [What is your rate of adenoma detection?].

PMID- 24923042
TI  - [Vitamin D supplementation: for and against in the BMJ!].

PMID- 24923043
TI  - [Infections related to implanted medical devices: the down-side of medical
      progress].

PMID- 24923044
TI  - [Implanted medical device-related infections: pathophysiology and prevention].
AB  - Medical progress led to an increase in the number of indications for indwelling
      devices. However, colonization of implanted devices by pathogenic microorganisms
      also increases risks of formation of microbial communities surrounded by an
      extracellular matrix called biofilms. Biofilms are able to survive in the
      presence of high concentrations of antimicrobials, therefore leading to treatment
      difficulties and exposing patients to the risk of infection recurrence. Because
      of these features, preventive measures reducing the risk of microbial
      contamination are cornerstone for the management of any patient carrying an
      indwelling device.

PMID- 24923045
TI  - [Long-term central venous catheter-related infections].
AB  - Long-term intravenous catheters (LTIVC) are standard practice for patients with
      chronic diseases such as cancer, digestive disease requiring total parenteral
      nutrition or end-stage renal disease. Even if they greatly improved patients'
      care, the use of LTIVC is also associated with microbial contamination and
      subsequent infection. These catheter-related infections are associated with
      morbidity, mortality and increased health-care costs. As patients carrying these
      LTIVC stay at home for their treatment (home parenteral nutrition for instance)
      or between cycles of treatment (antineoplastic chemotherapy or dialysis), it is
      mandatory that general practitioner and nurses are aware of recent data on the
      epidemiology, diagnosis and treatment of LTIVC-related infections.

PMID- 24923046
TI  - [Intracardiac infections related to implanted medical devices (defibrillators,
      valvular prostheses].
AB  - Due to increases in the number of patients with implantable intracardiac devices,
      the incidence of infectious complications related to these devices gradually
      increases. These infections may affect the generator, and will be diagnosed upon
      local signs (erythema, suppuration, externalization). It may also affect
      intravascular leads, with general symptoms, and a risk of valvular endocarditis
      (tricuspid), pulmonary emboli, and secondary infectious focus. The diagnosis
      relies on cultures of samples from the generator site, the explanted material,
      and blood, as well as on trans-esophageal echocardiography (TEE). The treatment
      requires explantation of all parts of the device, and appropriate use of
      antibacterial agents. Prosthetic valves endocarditis differ from native valve
      endocarditis in several aspects: it affects older patients with more
      comorbidities; coagulase negative staphylococci are more frequently involved; TEE
      is always necessary for the diagnosis and follow-up; prosthesis dehiscence is a
      common complication of paraprosthetic lesions; antibacterial regimens need to be
      reinforced; prognosis is worse. There is no significant difference between
      biological prosthesis (bioprosthesis), and mechanic valves regarding the risk to
      develop endocarditis, and its treatment.

PMID- 24923047
TI  - [Vascular prostheses-related infections].

PMID- 24923048
TI  - [Infections associated with orthopaedic devices].
AB  - Surgical site infections are a major complication of instrumented orthopaedic
      surgery, affecting 0.5 to 2% of patients following arthroplasty, and up to 30% of
      patients after fixation of open fractures. Acute infections may result from
      exogenous inoculation during or in the weeks following surgery (early
      infections), or from hematogenous seeding from a remote origin at any time after
      implantation (late infections). These infections are generally due to virulent
      organisms, such as Staphylococcus aureus, and must be treated rapidly. Delayed
      infections, arising between 3 and 24 months after surgery, are caused by low
      virulence organisms such as coagulase-negative staphylococci. Diagnosis of
      delayed infections may be difficult because clinical presentation is often subtle
      and limited to chronic pain, and relies on imaging studies and culture of
      synovial fluid aspirates. Strong collaboration between surgeon, microbiologist
      and infectious disease specialist is essential for management of implant
      associated infections, which almost always necessitates surgical intervention and
      prolonged antimicrobial therapy. The choice of the type of surgical intervention
      (debridement, or removal with or without exchange of the implant) depends on the
      duration of infection signs, on the pathogen species and antibiotic
      susceptibility, and on the patient general and local condition. Antibiotics are
      chosen according to pathogen susceptibility and to pharmacokinetic parameters
      such as bioavailability and penetration into the bone tissue. Patients treated in
      accordance with current guidelines are cured of their infection in 60 to 80% of
      cases.

PMID- 24923049
TI  - [Catheter-associated urinary tract infection].
AB  - Nosocomial urinary tract infections are the most common nosocomial infections.
      Their main risk factor is the urinary catheter The daily incidence of acquisition
      of microorganisms in the urine of a patient with a urinary catheter is 3 to 10%
      per day of catheterization, representing a cumulative risk of 100% after 30 days.
      The Gram-negative bacilli account for about two-thirds of isolated microorganisms
      led by Escherichia col. To prevent infections occurring with urinary
      catheterization, indications of the latter should be limited. When
      catheterization is essential, strict hygiene rules and proper use must be
      respected. Antibiotic treatment of infection with urinary catheter must take into
      account the diffusion of antibiotic, resistance of the main bacteria involved and
      patient characteristics.

PMID- 24923050
TI  - [Catheter-related suprapubic infections].

PMID- 24923051
TI  - [Peritoneal dialysis-related infections].

PMID- 24923052
TI  - [Biliary prostheses-related infections].

PMID- 24923053
TI  - [Neurosurgical material-associated infections].
AB  - Cerebrospinal fluid shunts (CSF) are frequently implanted in acute or chronic
      hydrocephalus. Intraoperative contamination is the main cause of infection of
      these devices. Causative germs are found mostly saprophytic (including
      Staphylococcus sp). The diagnosis can be easy, especially referred to a febrile
      meningeal syndrome, but also less intense, resulting in valve dysfunction.
      Therefore, in practice, any patient with CSF shunt should be suspected of being
      infected thereof, in case of fever and/or new or reappearing neurological
      symptoms, and until proven otherwise. The treatment is based on high-doses
      parenteral antibiotherapy, and more often removing the CSF shunt. Infections of
      cochlear implant are less common, and rarely deep. They are treated surgically by
      cleaning the surgical site, and in combination with systemic antibiotics. Their
      conservative treatment can be a concern.

PMID- 24923054
TI  - [Infections related to otorhinolaryngologic prostheses].

PMID- 24923055
TI  - [Breast implants-related infections].

PMID- 24923056
TI  - [Brain metastases: first, don't give up!].

PMID- 24923057
TI  - [Brain metastases: epidemiology, diagnosis and imaging].
AB  - The incidence of brain metastases is poorly documented but seems to be
      increasing. Brain metastases occur in 10% of patients with cancer. Extending the
      life of patients and improved diagnostic techniques seem to be the cause of this
      increase. The diagnosis is made either on systematic reviews of sick patients,
      either before the onset of a neurological disorder. Brain MRI is the gold
      standard to evaluate the number, size and location of brain metastases. Achieving
      an histological examination should be performed in cases of diagnostic
      uncertaintly. Inaugural metastases occure in 20% of cases. The general
      practionner should investigate primary cancer quickly to refer the patient to an
      appropriate specialist. The management of brain metastases is multidisciplinary
      and requires coordination of different practitioners.

PMID- 24923058
TI  - [Brain metastases: surgery and stereotactic radiosurgery].
AB  - Recent progresses in treatment of brain metastases have improved survival and
      quality of life in cancer patients. Surgery and stereotactic radiosurgery are two
      validated technics for brain metastases treatment. Actually, these two modalities
      of treatment could be used separately or in combination depending on the clinical
      situation (age, primitive disease status, type of primitive cancer, Karnofsky
      performance status) and radiological situation (number of brain metastases,
      localization). In this article, data from trials that examine the role of surgery
      and stereotactic radiosurgery in the management of brain metastases are reviewed.

PMID- 24923059
TI  - [The role of whole-brain irradiation in the treatment of brain metastases].

PMID- 24923060
TI  - [Chemotherapy and targeted therapies in the management of brain metastases].
AB  - In case of cancer dissemination to the brain, surgery and radiosurgery of all the
      brain metastases must be considered when possible. In other cases, whole brain
      radiotherapy remains the standard of care. The place of chemotherapy in this
      strategy remains debated. New targeted therapy, which might be even more
      efficient than cytotoxic chemotherapy, will probably challenge upfront
      radiotherapy in the next years to come.

PMID- 24923061
TI  - [Strategy and management in brain metastasis].
AB  - The brain metastases management has evolved over the last fifteen years and may
      use varying strategies including more or less aggressive treatments, sometimes
      combined, leading to an improvement in patients' survival and quality of life.
      The therapeutic decision is subject to a multidisciplinary, taking into account
      established prognostic factors including patient's general condition, extra
      cerebral disease status and clinical and radiological presentation of brain
      metastases. In this article, we propose a management strategy based on the state
      of current knowledge and available therapeutic resources.

PMID- 24923062
TI  - [Supportive care, cognitive assessment and quality of life after treatment for
      brain metastases].

PMID- 24923063
TI  - [Datasets: a triple evolution].

PMID- 24923064
TI  - [Evaluation of a pituitary adenoma].

PMID- 24923065
TI  - [Pituitary adenoma].

PMID- 24923066
TI  - [Epilepsy in the child and in the adult. Part 1. Epilepsy in the child].

PMID- 24923067
TI  - [Red and painful eye].

PMID- 24923068
TI  - [Measurement of the health status of the population].

PMID- 24923069
TI  - Beef up your discharge planning processes, experts recommend.
AB  - The Centers for Medicare & Medicaid Services is increasing its emphasis on
      discharge planning and has developed a worksheet for surveyors to use to
      determine if hospitals are in compliance with the Conditions of Participation.
      Hospitals must have discharge policies and procedures in writing and must be able
      to show that they are following them. Discharge planning assessments should be
      comprehensive and include the patient's psychosocial needs as well as medical
      needs and should take into consideration whether patients can safely go back to
      their previous setting. Communication with post-acute providers is essential to
      create smooth transitions and identify any gaps in information.

PMID- 24923070
TI  - Reaching out to post-acute providers.

PMID- 24923071
TI  - CMS mandates better DP earlier in the stay.

PMID- 24923072
TI  - Extending hospital to the primary care office.
AB  - Using a Centers for Medicare & Medicaid Services Innovation grant, Beth Israel
      Deaconess Medical Center in Boston launched a program to prevent readmissions.
      Care transition specialist nurses are assigned to six primary care practices and
      work with patients in the practice to which they are assigned. They meet patients
      in the hospital and follow them for 30 days after discharge. The program includes
      pharmacists who conduct medication reconciliation and work with patients on
      medication issues, and a social worker who is called in when patients have
      psychosocial needs.

PMID- 24923073
TI  - Community case management -- thinking beyond the hospital walls.
AB  - Case managers must approach the case management process as one that focuses
      across on the continuum of care and addresses inpatient as well as community
      needs. Case management assessments must go well beyond just the issues of
      discharge destination, but rather connect the care providers across the continuum
      in new ways that will improve outcomes for patients and reduce cost for the
      healthcare industry.

PMID- 24923074
TI  - HF readmissions drop after initiatives.
AB  - By analyzing heart failure readmissions and collaborating with post-acute
      providers and community organizations, Essentia Health-St. Joseph's Medical
      Center in Brainerd, MN, cut its readmission rate from 18% to a low of 6%. An
      interdisciplinary team analyzed readmissions, interviewed patients who were
      readmitted, and developed the program. Initiatives include setting primary care
      appointments while patients are in the hospital, following up after discharge,
      and creating order sets that include best practices. The hospital staff meet
      regularly with post-acute providers and social service agencies to brainstorm
      ways to create smoother transitions and ensure that patients get what they need
      after discharge.

PMID- 24923075
TI  - Nurses at high risk of work-family conflict.

PMID- 24923076
TI  - Subconjunctival bevacizumab injection in the surgery of primary pterygium:
      comparison with intraoperative mitomycin-C.
AB  - PURPOSE: To assess the efficacy of subconjunctival bevacizumab injection as
      adjuvant therapy in the prevention of recurrence following the surgical treatment
      of pterygium by comparison with intraoperative mitomycin-C application. METHODS:
      This prospective comparative study included thirty consecutive patients with
      primary nasal pterygium that were surgically treated with simple excision. In
      addition to surgical excision, subconjunctival bevacizumab was injected in 15
      eyes (group A), and, in the remaining 15 eyes, topical mitomycin-C 0.2 mg/mL was
      applied for 2 minutes (group B). The postoperative outcome was followed
      clinically for a minimum of 12 months. The main outcome criteria were recurrence
      rate and postoperative complications. RESULTS: A significantly higher recurrence
      rate was found in bevacizumab group (66.7%) compared to MMC group (26.7%) (P=
      0.028). In group A, conjunctival wound separation was observed in 3 of 15 eyes;
      however, no conjunctival separation was observed in Group B and no other serious
      complications were observed in either group. CONCLUSION: The intraoperative use
      of subconjunctival bevacizumab does not seem to be effective in reducing the rate
      of pterygium recurrence following excision when compared with intraoperative
      mitomycin-C application.

PMID- 24923077
TI  - The effect of different doses of subconjunctival bevacizumab on the recurrence
      rate of excised primary pterygium.
AB  - PURPOSE: To evaluate the safety of different doses of subconjunctival bevacizumab
      and their effects on the recurrence rate after primary pterygium excision.
      METHODS: This prospective randomized placebo-controlled clinical study was
      conducted on 59 eyes (59 patients). The visual acuity, refractive astigmatism,
      horizontal length of the pterygium, and recurrence risk factors were recorded.
      There were no statistically significant differences between the groups for age,
      sex, horizontal length of pterygium, preoperative visual acuity, astigmatism, and
      recurrence risk factors. The pterygium was excised from the conjunctival side and
      then peeled off the cornea. The bare sclera was covered with a rotational
      conjunctival flap from the superonasal area. After surgery, Group 1 (22
      patients), Group 2 (17 patients) and Group 3 (20 patients) received 7.5 mg
      bevacizumab, 2.5 mg bevacizumab, and Balanced Salt Solution (BSS)
      subconjunctivally, respectively. Postoperatively, horizontal length of corneal
      epithelial defect, conjunctival congestion, and lacrimation were checked on the
      first and seventh day. The rate of recurrence (>1.5 mm fibrovascular overgrowth
      on the cornea) at month 6 was compared between the groups. RESULTS: There were no
      statistically significant differences between the groups for all measured
      variables except for moderate conjunctival congestion on the first postoperative
      day which was more common in the bevacizumab groups (P=0.002). Four eyes in
      Groups 1 (20%) and 2 (26.7%) and 3 in Group 3 (15.8%) experienced recurrence
      (p=0.73). All recurrences occurred at month 3 and subsequently thereafter.
      CONCLUSIONS: In our study, perioperative injections of subconjunctival
      bevacizumab had no effect on primary pterygium recurrence and were not associated
      with any specific local complications.

PMID- 24923078
TI  - Ocular syphilis, a case of acute posterior placoid chorioretinitis.
AB  - PURPOSE: To report a case of acute posterior placoid chorioretinitis, a rare
      manifestation of ocular syphilis. METHODS: The patient was examined at age 59
      with symptoms of subacute severe unilateral vision loss of the right eye. He
      underwent fundus examination, automated perimetry, optical coherence tomography
      imaging and fluorescein angiography. There was a close follow-up for 3 months.
      RESULTS: At time of presentation, the visual acuity in the right eye was hand
      movement. Fundus examination showed a central retinal placoid yellowish lesion
      going beyond the temporal vascular arcades. Optical coherence tomography showed
      thickening of the neuroretina and disappearance of the inner and outer segment
      junction. Fluorescein angiography showed in the early phase areas of
      hypofluorescence followed by hyperfluorescence and late staining. Serologic
      examinations were positive for secondary syphilis. After treatment with
      intravenous ceftriaxone 2g/d for 2 weeks there was a complete functional recovery
      with regression of the fundus lesion. CONCLUSIONS: Acute syphilitic posterior
      placoid chorioretinitis has been described as a rare chorioretinal manifestation
      in patients with syphilis. The pathogenesis of this entity still remains unknown.
      Since there are no pathognomonic features of ocular syphilis, findings may often
      mimic those of other diseases. Maintaining an awareness of the different
      manifestations of this disease allows ophthalmologists to play a key role in the
      early diagnosis of syphilis.

PMID- 24923079
TI  - Giant cell arteritis: the internist should not be a lone rider in this
      potentially blinding condition.
AB  - We report the case of a 66-year-old woman with visual loss due to anterior
      ischaemic optic neuropathy. The diagnosis of giant cell arteritis was made on the
      basis of classic clinical characteristics and haematological abnormalities.
      Despite corticosteroid treatment, involvement of the other eye occured, resulting
      in a bilateral and permanent loss of vision. The follow-up was marked by two
      relapses within the 6 months after the first episode. In order to prevent
      blindness, ophthalmologists should be familiar with this disorder and should
      actively participate in the treatment, not leaving the internist deciding alone
      about tapering corticotherapy.

PMID- 24923080
TI  - [Maculopathy and dengue fever].
AB  - The authors report a case of a 20 year old female who presented a bilateral
      decrease in vision. Detailed history revealed that 15 days before the onset of
      symptoms, the patient presented a dengue fever during her stay in Martinique. On
      initial examination, the fundus exam revealed a bilateral loss of foveal
      reflection. The optical coherence tomography demonstrated the macular edema and
      the dengue serology was postive. The patient received an interferon2a-based
      therapy. The macular edema disappeared and we noticed a partial but fast
      improvement of visual acuity 12 days after the treatment initiation.

PMID- 24923081
TI  - Benefit of surgery in presence of orbital metastasis.
AB  - PURPOSE: Malignant tumors metastatic to the orbit are rare and only about 5% of
      orbital tumors are metastasis. We report on orbital surgery in a patient with
      orbital metastasis from small cell lung carcinoma (SCLC). METHODS: A 75-year-old
      man complained of pain in the left orbital region and proptosis. Head CT scan
      showed a left retrobulbar mass compressing the optical nerve. Chest and body CT
      scans showed a round-shaped mass at the apex of the left inferior lobule of the
      lung and widespread nodal involvement. RESULTS: A surgical intervention on the
      left orbit through a lateral approach was performed, with complete removal of the
      mass. Histology showed features of a non-anaplastic SCLC. A complete restoration
      of visual acuity was obtained CONCLUSIONS: A debulking orbital surgery, in order
      to relieve optic nerve compression, should be offered to the patients with
      orbital metastasis.

PMID- 24923082
TI  - [Spontaneous peeling of the epimacular membrane after cryotherapy of retinal
      vasoproliferative tumors: report of a case].
AB  - Epimacular membranes when responsible for a significant loss of visual acuity,
      generally require treatment by vitrectomy and peeling of the membrane. We report
      the case of a spontaneous peeling of a macular pucker after cryotherapy of
      peripheral retinal vasoproliferative tumors. Review of the literature.

PMID- 24923083
TI  - Vitrectomy in uveitis patients.
AB  - PURPOSE: To evaluate the causes and success rates of pars plana vitrectomy (PPV)
      in uveitis patients. METHODS: Retrospective study of the charts of 26 uveitis
      patients (28 eyes) who underwent PPV between the years 2008 and 2011. We examined
      surgical indications and success rates, based on visual outcomes, complications
      and diagnosis in case of vitreous biopsy. RESULTS: (1) Therapeutic PPV (TV) was
      performed in 36% of the eyes, (2) TV combined with epiretinal membrane (ERM)
      peeling in 21% and (3) diagnostic PPV (DiV) was performed in 64% of the eyes.
      Eight eyes (28,6%) underwent a combined cataract and vitreous surgery. Visual
      acuity (VA) improved in 16 eyes (57%), with a mean improvement of -0,9 log of the
      minimum angle of resolution (logMAR), although the effect was transient in 7% of
      the cases. VA remained stable in 11 eyes (39%) and decreased in 1 (4%). Post
      operative complications were cystic macular oedema (CMO) in 3 eyes (11%),
      cataract in 5 eyes (18%) and retinal detachment in 2 eyes (7%). Diagnostic tests
      were performed in 18 eyes with a success rate of 55%. CONCLUSIONS: In our series
      of patients with uveitis, a good andstable improvement of VA was found when PPV
      was performed with ERM peeling while the effect on VA was more transient in the
      other cases. A good success rate of diagnosis was also found in DiV. However,
      considering the possible severe complications, diagnostic vitrectomy should be
      limited to selected cases.

PMID- 24923084
TI  - Bifocal optic and facial nerve t-cell lymphoma.
AB  - PURPOSE: Optic nerve and optic nerve sheath infiltration by a systemic lymphoma
      is uncommon, but is exceedingly rare when caused by a T-cell lymphoma. This then
      generally occurs in association with central nervous system (CNS) involvement. We
      report on a rare case of optic and facial nerve T-cell lymphoma infiltration,
      without CNS involvement. METHODS: A 63-year old female with systemic T-cell
      lymphoma in clinical remission presented with painful loss of vision in the left
      eye. She was initially treated for presumed recurrent optic neuritis. A thorough
      clinical work-up was performed, followed by an optic nerve biopsy with
      histopathology. RESULTS: There was no perception of light in the left eye, with a
      marked relative afferent pupillary defect. Fundoscopy showed significant optic
      disc oedema and a large peripapillary subretinal infiltration. Subsequently, she
      developed a 7th cranial nerve paresis. Cranial MRI showed thickening and contrast
      enhancement of the left optic nerve and right facial nerve. Optic nerve biopsy
      showed infiltration of CD3- and CD5- positive lymphocytes. A complete systemic
      workup revealed no evidence of disease elsewhere. The patient was thus considered
      to have bifocal cranial recurrence of T-cell lymphoma, for which radiotherapy was
      started. CONCLUSIONS: Optic nerve infiltration from systemic lymphoma is rare and
      generally occurs with CNS involvement. A bifocal pattern of recurrence from
      systemic T-cell lymphoma involving the right facial nerve and left optic nerve
      was seen in this patient. A review of the literature highlights the highly
      atypical nature of this presentation.

PMID- 24923085
TI  - Cancer associated retinopathy with periphlebitis and bilateral vitreous
      hemorrhage.
AB  - INTRODUCTION: Cancer associated retinopathy (CAR) is an uncommon paraneoplastic
      syndrome associated with epithelial neoplasm. Ocular symptoms of this syndrome
      are varied. CASE REPORT: A 40-year-old man with an existing smoking history
      noticed a bilateral visual loss.Fundus examination showed a bilateral vitreous
      hemorrhage.In the left eye, there were narrowed retinal arterioles and
      peripapillary neovessels. An X-ray chest revealed a lung lesion which on biopsy
      proved to be a bronchial squamous cell carcinoma. After conducting several
      explorations,we have diagnosed CAR. CONCLUSION: Vitreous hemorrhage is one of the
      symptoms of CAR. Thus, systems review, searching for an extraocular cancer, X-ray
      chest and ERG are recommended in this case.

PMID- 24923086
TI  - Lens subluxation with stretched ciliary processes in a girl with Goltz syndrome.
AB  - PURPOSE: To report lens subluxation with additional stretching of the ciliary
      processes as ocular features of Goltz syndrome. METHODS: Case report. RESULTS: A
      now 4-year old girl was diagnosed at birth with Goltz syndrome. Best-corrected
      visual acuity was 1/60 in both eyes. Slitlamp examination showed bilateral iris
      colobomata and inferior subluxation of the lens with abnormally stretched ciliary
      processes. Funduscopy revealed bilateral chorioretinal and optic disc colobomata.
      CONCLUSIONS: Ocular anomalies are often associated with Goltz syndrome. Although
      ectopia lentis is a known ocular feature, this is the first case of lens
      subluxation with additional, abnormally stretched ciliary processes.

PMID- 24923087
TI  - Pseudoxanthoma elasticum confirmed by genetic analysis but not by skin biopsy: a
      case report and review of the literature.
AB  - In patients with angioid streaks, additional investigations are useful to
      identify underlying systemic disease, unless age and short peripapillary streaks
      are indicative of senile streaks as an isolated abnormality. In middle-aged or
      young adults with angioid streaks and no obvious systemic disease, the
      possibility of a hemoglobulinopathy or pseudoxanthoma elasticum (PXE) as
      etiologic entities should be investigated. Hemoglobinopathies can be excluded
      based on blood screening and the absence of typical ocular fundus changes, such
      as retinal vessel tortuosity. This allows making a presumed clinical diagnosis of
      PXE in patients with angioid streaks, based on exclusion of a hemoglobinopathy,
      and on the presence of extensive angioid streaks, peau d'orange, crystalline
      bodies and comet tail lesions. For confirmation of PXE, the gold standard was
      dermatologic examination and skin biopsy, but since the last decade molecular
      diagnosis is available. In rare cases, PXE can be diagnosed using molecular
      techniques in patients with apparently normal skin and negative skin biopsies, as
      demonstrated in this case and another case published in 2011.

PMID- 24923088
TI  - The range of the waveform score of the ocular response analyzer (ora) in healthy
      subjects.
AB  - PURPOSE: The waveform score (WS) indicates the reliability of each intraocular
      pressure (lOP) measurement signal performed with the Ocular Response Analyzer
      (ORA, Reichert). We aimed to assess i) the range of waveform score in IOP
      measurements with ORA in healthy subjects and to ii) identify a cut-off WS value
      under which an ORA measurement should be discarded. METHODS: Prospective study
      including three ORA IOP measurements performed in the right eye of 80 healthy
      normal subjects. The different WS were recorded and the highest WS of the three
      measurements was analysed. ANOVA test was used to assess variance in repeated
      measurements. RESULTS: Mean age of 80 subjects was 46.7+/-15.6 years. Mean WS of
      the first IOP measurement was 4.8+/-2.0 and 4.8+/-1.7 and 5.0+/-1.9 respectively
      for the second and third measurements (p= 0.74). Mean WS of the analysed 240
      signals (3 measurements per eye) was 4.9+/-1.9 (range: 1.2-9.5). The mean value
      of all the highest values per eye was 6.2+/-1.8 (range: 2.9 -9.5 and was
      significantly higher than the mean WS of the 240 signals together (p <0.001). The
      10th percentile of all the best values was 3.7 and the 75th percentile 7.5.
      CONCLUSION: ORA measurements with WS <3.7 should be discarded in healthy normal
      subjects. As much as that the corresponding quality of the waveform ORA scan is
      satisfying, one single measurement with a WS >7.5 could be considered as
      sufficient. If this score cannot be reached after three consecutive measurements,
      the signal with the highest WS should be selected.

PMID- 24923089
TI  - [Palpebral pilomatricoma simulating a chalazion in a young adult].
AB  - The pilomatricoma or epithelioma of Malherbe is a mummified benign and rare skin
      tumor. We report a rare case of palpebral pilomatricoma simulating a chalazion in
      a 26-year-old patient. This skin tumor is exceptional in adults. Its diagnosis is
      often missed preoperatively because of its great clinical polymorphism and is
      histopathologically based on the detection of mummified cells. Its surgical
      treatment will aim at a complete excision of the tumour in order to minimize the
      risks of recurrence.

PMID- 24923090
TI  - Long term IOP lowering efficacy of bimatoprost/timolol fixed combination: a 12
      month prospective study.
AB  - PURPOSE: To evaluate the long-term IOP-lowering effect of an initially successful
      switch from prostaglandine-analog (PGA) monotherapy to bimatoprosttimolol fixed
      combination (BTFC) METHODS: Prospective, monocentric, open-labeled clinical
      trial. 30 patients with insufficient intraocular pressure (lOP) control under PGA
      monotherapy were screened. Following a one month run-in period of BTFC, patients
      who presented an effective IOP-lowering response were prospectively studied for
      an additional 11-month period. IOP, tolerability and safety (adverse reactions,
      slit lamp biomicroscopy) were further assessed at month 6 and month 12 after
      initiating BTFC. RESULTS: BTFC therapy significantly decreased IOP when compared
      to PGA monotherapy (PGA monotherapy: 17.3+/-3.8 mmHg; BTFC 1 month 13.2+/
      3.3mmHg; p<0.05). This decrease from PGA-monotherapy IOP was sustained throughout
      the time-frame (6-month: 13.5+/-3.6mmHg; 12-month: 13.9+/-2.4mmHg; p<0.05 in
      pairwise comparison). There was no statistical difference in IOP between BTFC
      study visits (p>0.05). Of the 27 patients who had a satisfactory lOP-lowering
      response to BTFC after one month, 18 (66.7%) still had sufficient IOP control at
      the 12 month study visit. Therapy was discontinued at 1 month in 3 patients (2
      due to intolerance to medication and 1 failing to achieve IOP control). No
      intolerability was reported beyond the 1 month of BTFC therapy. CONCLUSION: In
      the majority of patients, the initial lOP lowering effect of replacing PGA
      monotherapy by BTFC seems to predict a long term response to the new treatment
      strategy.

PMID- 24923091
TI  - [Management of rhegmatogenous retinal detachment with unseen breaks: about 50
      cases].
AB  - PURPOSE: To evaluate the clinical and therapeutic characteristics of
      rhegmatogenous retinal detachment (RRD) with unseen retinal breaks. PATIENTS AND
      METHODS: Retrospective study 50 eyes (50 patients) with RRD with unseen retinal
      breaks in the pre and intraoperative examination. These patients were treated
      between 2005 and 2010 by vitrectomy or scleral buckling. Retinal breaks were
      meticulously sought by indentation of the vitreous base. The subretinal fluid was
      drained by a peripheral retinotomy when a vitrectomy was needed and puncture ab
      externo when a scleral buckling was performed. RESULTS: A retinal detachment with
      unseen retinal breaks accounted for 15% of all RRD operated during this 5-year
      duration period (2005 - 2010). The average age of our patients was 57 years.Ten
      were myopic (20%) and 27 (54%) pseudophakic, with inferior RRD in 60% of the
      cases cases while advanced vitreoretinal proliferation (PVR) greater or equal to
      stage C in was present in 72%. Primary vitrectomy was performed in 46 cases.
      Retinal reattachment rate was achieved after a single procedure in 41 eyes (82%).
      Among them, 40 were operated by vitrectomy and one eye by scleral buckling. The
      recurrence rate was significantly higher in patients operated by scleral buckling
      (75%) than by vitrectomy (15%). CONCLUSION: RRD with unseen retinal breaks are
      often seen inferiorly and have a chronic evolution (60%). They concern
      pseudophakic patients in the majority of the cases. Their poor prognosis and high
      recurrence rate also appear to be related to an advanced PVR (72%). The good
      results of primary vitrectomy should be confirmed by randomized studies,
      especially in phakic eyes.

PMID- 24923092
TI  - [Ocular manifestations of children living with HIV/AIDS in Kinshasa].
AB  - OBJECTIVE: to determine the frequency of ocular manifestations in Congolese
      children aged 0 to 15 years infected with HIV/AIDS and to identify the predicted
      clinical and/or biological elements. METHODS: This was a prospective, descriptive
      and cross-sectional study performed from November 2010 to April 2011 in five
      sanitary structures who take care of children infected with HIV/AIDS. During the
      period of study, one hundred children infected with VIH/AIDS were examined.
      Seventy- six (76%) of children were under highly active anti-retrovial therapy
      (HAART). The age of children ranged from 0,5 month to 15 years. Children
      underwent a routine ophthalmic examination which included measurement of visual
      acuity, inspection of the adnexa and cornea, slit-lamp examination and dilated
      ophthalmoscopy. The CD4 lymphocyte count was determined in 88 of them. RESULTS:
      The frequency of ocular manifestations was 36%. The mean age of children was 8
      years (SD: 4.01; range 0,5 month-15 years). The male female sex ratio was 0.8/1.
      Ocular complaints were present in 22 children (22%). Visual symptoms were most
      frequent in children with severe decrease of immunity. Of four children
      identified with a visual handicap, one (1.5%) had blindness and three (4.4%) had
      visual impairment. All of these four children had a CD4 lymphocyte count less
      than 15%. Among ocular manifestations, the adnexial manifestations were the most
      frequent with 18 cases (18%) followed by the posterior segment manifestations
      with 14 cases (14%) and the neuroophthalmic lesions with 5 cases (5%).
      CONCLUSION: This study documented 36% of ocular manifestations; this frequency is
      comparable with the other African studies. Comparatively to studies conducted in
      other continents the frequency in African studies is high. This study also showed
      that the adnexial manifestations are the most frequent ocular findings and that
      the children with severe decrease of immunity are most exposed to visual troubles
      that can lead to blindness.

PMID- 24923093
TI  - [Marcus Gunn Syndrome. Study of 3 rare cases].
AB  - PURPOSE: reporting three rare cases of Marcus Gunn Syndrome and analyzing the
      clinical features of this entity. METHODS: Case reports of three patients with a
      Marcus Gunn Syndrome, treated at the Ophthalmology B CHU service Rabat - Morocco.
      RESULTS: Our patients are two boys aged 1 and 2 years old, and a 31 year old
      woman with a Marcus Gunn Syndrome. As special features, in the boys' cases this
      syndrome is bilateral, as for the other case it is associated with congenital
      fibrosis clinically predominant of the Ipsilateral inferior rectus muscle in an
      adult. Surgical treatment was not offered for children because of their young
      age. The adult patient has benefited from a recession of the inferior rectus
      muscle and a pleating in the superior rectus muscle. The forced duction test
      objectified a fibrosis of the inferior rectus muscle. Surgical correction of
      Ptosis and Synkinesis has not been indicated in this patient, given the residual
      oculomotor disorder and the risk of exposure keratitis. CONCLUSION: Marcus Gunn
      Syndrome is exceptional in adults. This can be explained by the tendency of the
      lid retraction to fade with age. Bilateral involvement in Marcus Gunn Syndrome is
      rare. Its association with congenital fibrosis of extraocular muscles has allowed
      a better etiopathogenic approach highlighting a supra nuclear origin of this
      Syndrome.

PMID- 24923094
TI  - Didactic image poppers maculopathy.
AB  - We describe a case of toxic maculopathy caused by unique inhalation of poppers.
      This maculopathy has spontaneously resolved.

PMID- 24923095
TI  - [How I explore and treat a neonatal renal vein thrombosis: a case report].
AB  - Neonatal renal vein thrombosis is a rare condition. The present case is rather
      unfrequent and particularly educative since it shows the complete diagnostic
      triad including hematuria, flank mass and thrombocytopenia. The diagnosis relies
      on the demonstration, by Doppler ultrasound, of an obstructed renal venous bed.
      The investigation is completed by a platelet count and the determination of the
      prothrombin time, of the activated partial thromboplastin time as well as of the
      concentration of fibrinogen. The screening also includes the search for a
      possible etiology, such as a deficiency in coagulation proteins, the presence of
      antiphospholipid antibodies or of a genetic mutation of one of the coagulation
      factors. Since there exist no evidence based guidelines for the management of the
      disease, we will discuss the diagnosis and treatment in relation with the
      published literature.

PMID- 24923096
TI  - [Blue baby syndrome: the source of the truth].
AB  - Methemoglobinemia is a rare disorder preferentially affecting children. The
      outcome may be dramatic when the disorder remains unidentified, however early
      recognition using unspecific exams allows prompt therapy. We report the case of a
      14-month-old baby who presented with a sudden access of cyanosis resulting from
      acute methemoglobinemia. Careful investigation identified contamination of
      familial food by an excess of nitrates related to the use of well water from
      rural location.

PMID- 24923097
TI  - [European Society of Cardiology guidelines on cardiac resynchronization therapy].
AB  - Cardiac resynchronization therapy (CRT) is one of the most successful heart
      failure therapies to emerge in the last 25 years; it is applicable to > 25-30% of
      patients with symptomatic heart failure. In this article, we summarize the
      recommendations of the European Society of Cardiology of 2013 on cardiac
      resynchronization therapy.

PMID- 24923098
TI  - [Cancer and the right to motherhood].
AB  - As a result of advances in the field of oncology, cancer survival rate has
      improved at the cost of sequelae in terms of fertility with a possible loss of
      ovarian function in girls. To alleviate the consequences of this iatrogenic
      menopause, various options are available. Cryopreservation of ovarian cortex,
      allowing the preservation of immature cells, is one of the best solutions and
      gave birth to 24 children worlwide. These results make it legitimate to propose
      freezing ovarian tissue for pediatric patients or young adult women undergoing
      potentially sterilizing treatment. The decision has to be discussed with the
      patient and/or his legal representative, the oncologist and gynecologist.

PMID- 24923099
TI  - [Role of general practioners in the follow-up of bariatric surgery in the
      province of Liege].
AB  - This paper is concerned with the place and role of general practitioners in the
      follow-up of patients submitted to bariatric surgery in the province of Liege.
      The results of the analysis were compared with clinical practice guidelines
      published by the French Haute Autorite de Sante (HAS). Fifteen interviews were
      conducted with GPs who follow up operated patients. The results highlight the
      GPs' wish to fully participate in the follow-up of those patients. Their medical
      supervision is centered on the HAS clinical practice guidelines, taking into
      account the intake deficiencies as well as the patient's psychological
      experience. However, some aspects are disregarded, mainly because of a lack of
      theoretical knowledge (some biological parameters, pregnancy and contraception).
      The short consultation time along with the poor communication with the hospital
      multidisciplinary team were mentioned as obstacles to a good quality follow-up.
      Progress is still needed to reach the clinical practice guidelines. However,
      there is a wish to better collaborate. Organising coordination meetings between
      professionals along with an early implication of the GP - even before surgery -
      represent possible solutions.

PMID- 24923100
TI  - [Levels of target achievement for major modifiable cardiovascular risk factors in
      Belgium].
AB  - Cardiovascular disease (CVD) is the main cause of premature mortality in Europe.
      The burden of CVD could be reduced by controlling the major modifiable CVD risk
      factors (dyslipidaemia, arterial hypertension, hyperglycaemia, smoking, and
      physical inactivity) through lifestyle and dietary changes and appropriate drug
      therapies. The objective of this article is to assess the level of target
      achievement for key modifiable CVD risk factors in Belgium by referring to the
      data from four recent studies. The overall results show that the main CVD risk
      factors are poorly controlled in patients with established CVD and in patients at
      high CVD risk. Therapeutic targets may be incompletely reached because of the
      suboptimal implementation of European guidelines for CVD prevention in routine
      clinical practice (insufficient lifestyle and dietary adaptations; poor
      applications of drug therapy to control blood pressure, dyslipidaemia and
      hyperglycaemia) or because of the insufficient efficacy of currently available
      treatment options in some patients. This review provides clear and updated
      evidence for non-target achievement for all major risk factors, with four
      different study designs and inclusion criteria; it highlights the need for a more
      comprehensive and intensive application of recommendations of the European
      guidelines for CVD prevention in Belgium.

PMID- 24923101
TI  - [Dermatoporosis, a vintage for atrophoderma and transparent skin].
AB  - Skin ageing occasionally manifests itself at long-term by severe atrophoderma.
      Systemic or topical corticotherapy exerts an atrophic impact mimicking the
      effects of old age. Such atrophoderma condition has been described as transparent
      skin about 40 years ago, and it received more recently the new denomination of
      dermatoporosis. Such condition stands out in the medical history to induce
      clinical consequences. They are sometimes prominent introducing diverse lesions
      such as Bateman purpura, stellate scars and wounds following minor trauma.

PMID- 24923102
TI  - [Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR)].
AB  - Bydureon is a new galenic formulation (long-acting release) of exenatide, the
      first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been
      commercialized for the management of type 2 diabetes. The microsphere technology
      permits a prolonged absorption of exenatide from the subcutaneous depot, which
      allows one injection per week instead of two injections per day with the initial
      formulation of exenatide (Byetta). The clinical development programme DURATION
      showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin
      (HbA(1c)), with a similar weight loss but a better digestive tolerance profile
      (less nausea and vomiting after treatment initiation), compared with the twice
      daily 10 microg exenatide. When compared to other glucose-lowering agents, once
      weekly exenatide is more efficacious than sitagliptin, pioglitazone or basal
      insulin (glargine or detemir), with the advantage of producing weight loss and
      lowering arterial blood pressure. It does not induce hypoglycaemia and does not
      necessarily require home blood glucose monitoring, two advantages compared with
      insulin therapy. Bydureon is currently only reimbursed in Belgium after failure
      of and in addition to metformin-sulfonylurea combination.

PMID- 24923103
TI  - [Ulipristal acetate (Esmya): a selective modulator of progesterone receptors, new
      treatment of uterine fibromatosis].
AB  - Uterine fibromatosis is a frequent benign gynaecological disease causing heavy
      menstrual bleeding and in some cases anaemia. Until now, medical treatment aimed
      to obtain amenorrhea by administration of progestins or Gn-RH agonists. By
      inducing hypo-oestrogenism, a reduction of myoma size is observed with Gn-RH
      agonists but after cessation of the treatment, initial myoma size is noted. The
      impact of progesterone in myoma growth is nowadays demonstrated and use of
      selective modulators of progesterone receptors represents a new medical approach
      of this disease.

PMID- 24923104
TI  - [Management of acute cholangitis].
AB  - Treatment of acute cholangitis requires antibiotics and biliary drainage. Some
      patients develop a life threatening form requiring intensive care and urgent
      drainage. It is important to identify those patients as soon as possible.

PMID- 24923105
TI  - Phenotypic profiles of virulence in different Candida species isolated from
      vulvovaginal infections.
AB  - In order to establish an infection, pathogenic microorganisms have to colonize,
      survive, multiply, evade the immune system and spread to other tissues [1, 2, 3].
      Although some Candida species are normally commensal in humans, in the last
      decades the frequency and the severity of nosocomial diseases due to Candida
      strains have increased dramatically [4]. The aim of the present study was to
      characterize some Candida strains isolated from vulvovaginal infections by
      determining the virulence and pathogenicity profile. The assessment of the in
      vitro expression of virulence cell wall associated factors (hyphal formation,
      adherence to HeLa cell line, biofilm development), soluble secreted enzymes
      (aspartyl protease, lipase, phospholipase, DN-ase) and Fe3+ accumulation was
      achieved by phenotypic methods on 13 yeast strains belonging to five Candida (C.)
      species (C. albicans, C. krusei, C. parapsilopsis, C. catenulata and C. kefyr).
      Candida sp. strains isolated from vulvovaginal infections showed species/ strain
      specific virulence profile.

PMID- 24923106
TI  - Selection of bacterial strains efficient in decolorization of remazol black-B.
AB  - Azo dyes are released into wastewater streams without any pretreatment and
      polluted water and soil environments. To prevent contamination of our vulnerable
      resources, removal of these dye pollutants is of great importance. For this
      purpose, wastewater samples were collected from dye-contaminated sites of
      Ankleshwar, Gujarat, India. About 50 bacterial isolates were isolated through
      enrichment and then tested for their potential to remove Remazol Black-B azo dye
      in liquid medium. Three bacterial isolates capable of degrading Remazol Black-B
      azo dye efficiently were screened through experimentation on modified mineral
      salt medium. Isolate ETL-1 was able to completely remove the Remazol Black-B dye
      from the liquid medium in 18 h. Further, the isolate showed the best performance
      at the dye concentration of 100 mg L-1 medium (pH 7) and at temperature 35
      degrees C. Similarly, yeast extract proved to be the best carbon source for
      decolorization purpose. The results imply that the isolate ETL-1 could be used
      for the removal of the reactive dyes from textile effluents.

PMID- 24923107
TI  - Single and multipathogen viral infections in hospitalized children with acute
      respiratory infections.
AB  - We aimed to describe the viral etiology of acute respiratory tract infections in
      children aged 0-8 years admitted to Grigore Alexandrescu Hospital, the largest
      pediatric hospital in Romania. The patients had clinical diagnosis of pneumonia,
      bronchiolitis or viral respiratory infections and had been hospitalized between
      September 2010 and September 2011. The study was part of the "Molecular
      investigations of acute respiratory infections caused by non-influenza viruses,
      to assess the implications of infant and young child pathology" (2008-2011), a
      National Project II--42-164 (MIRVI). We included in the study 241 children that
      were swabbed in the first 8 days of the onset with the following symptoms during
      the previous 7 days: fever > 38 degrees C, AND cough or sore throat, and
      shortness of breath or difficulty breathing .We identified by RT-PCR 131 (54.4%)
      positive samples: 112 (85.5%) for a single pathogen, 18 (13.7%) for coinfection
      with two pathogens and 1(0.8%) for coinfection with three pathogens. The most
      frequent pathogen identified was respiratory syncytial virus (RSV) (40.18%),
      followed by Rhinovirus (RhV) (20.54%) and human Metapneumovirus (hMPV) (12.50%).
      We extrapolated our data to the National program of surveillance of SARI (severe
      acute respiratory infections). In this program, 191 children aged one month-8
      years, were hospitalized in the same period, in which the highest percentage of
      positivity was due to Influenza viruses (62.65%), but RSV was identified with
      almost the same percent like in MIRVI (32.53%). It should be noted that among
      patients with pneumonia, bronchiolitis or respiratory viral infections were
      identified as the causal agent RhV.

PMID- 24923108
TI  - Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy
      adolescents and adults in Iran.
AB  - Serologic data on diseases that are preventable by vaccine are useful to evaluate
      the success of immunization programs. In this study we evaluated the serologic
      levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional
      study, a total of 360 people aged 10-25 years were randomly selected and
      classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people
      aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1
      IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1
      IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to
      protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis
      toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels.
      Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to
      54.6 % in aged 21-25 years. No differences were found between male and female,
      except for diphtheria in age group 21-25 years. Results of this study reveal that
      diphtheria and tetanus (dT) are efficient between booster doses. About pertussis,
      most people are susceptible to pertussis and increased PT antibodies with age
      suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis
      infections in adolescents and adults are of concern, as they are the most
      important source of transmission of pertussis to young, unprotected infants. So
      one booster dose in adolescents and adults (as CDC recommended), to reduce
      mortality and morbidity in infants, is therefore suggested.

PMID- 24923109
TI  - Resveratrol modulates apoptosis in 5-fluorouracyl treated colon cancer cell
      lines.
AB  - Since cancer is a cellular disease, it is essential to identify the development
      stages and use the information in the prediction, prevention, early detection and
      design of drug targets. Colon cancer represents a malignancy with high incidence
      and mortality throughout the world, its etiology involving many genetic,
      immunological and biochemical factors. 5-fluorouracyl (5-FU) is one of the most
      effective anti-cancer agents used in the treatment of colorectal cancers, but
      tumor chemoresistance is a major limiting factor of its use. In order to choose
      the most effective chemotherapeutic doses of 5-FU, and thereby diminish the side
      effects, we tried to modulate the anticancer properties of 5-FU by adding dietary
      natural compounds. The study focused on the role of natural compounds as
      resveratrol (RSV) in sensitization of LoVo human colon adenocarcinoma cell line
      to 5-FU action. Real-time cell analysis (RTCA) by xCELLigence System was used to
      continuously monitor the cytotoxic effects of drug treatments on LoVo cells. RTCA
      allowed us to choose the proper concentrations for further end-point assays, such
      as flow-cytometry techniques used for the evaluation of apoptotic events,
      progression through cell cycle phases or nuclear antigen expression of compound
      treated LoVo cells. Data obtained showed additional effects of RSV to 5-FU
      treatments on the increase ofapoptotic events, and suggested alternative
      approaches to obtain a stronger antitumor response, and diminished side-effects
      when low concentrations of anti-cancer drugs are used. Modulation of the
      mechanisms of programmed cell death process seem to be of great importance for
      malignant transformation, and therefore for anti-cancer therapeutic approaches.

PMID- 24923110
TI  - [Treatment of venous trophic ulcers, using echoscleroobliteration of perforant
      veins].
AB  - In 36 patients, suffering trophic ulcers on a chronic venous insufficiency
      background in a decompensated stage (C6 in accordance to CEAP),
      echoscleroobliteration of perforant veins, using a "foam-form" method in
      accordance to Tessari, was performed. In 29 patients postrombophlebitic syndrome
      in incomplete recanalization stage was diagnosed, in 7 recurrence of varicose
      disease of the lower extremities. In all the patients during
      echoscleroobliteration there was possible to obliterate the insufficient
      perforant veins, in 3 patients two perforant veins were obliterated in each of
      them. In a one week a pathological blood flow along perforant veins, in
      accordance to data of ultrasound duplex scanning, was absent. This effect lasted
      during 6 mo in 29 (80.6%) patients. In 25 (69.4%) patients a trophic ulcers
      healing was achieved in 1 - 3 mo. In a one year in 30 (83.3%) patients a stable
      obliteration was noted, in 3 (8.3%) - partial recanalization, in 3 (8.3%) -
      complete recanalization of perforant veins.

PMID- 24923111
TI  - [Senning operation as a method of treatment of the main vessels transposition].
AB  - Results of performance of Senning operation for the main vessels transposition
      were analyzed. Analysis of complications, lethality in early postoperative period
      and of far-remote results was conducted. The systemic right ventricle function in
      patients after Senning operation was estimated. Not high level of early and late
      postoperative lethality was established. Clinical state of patients in far-remote
      postoperative period was good. A systemic right ventricle function was estimated
      as satisfactory.

PMID- 24923112
TI  - [Prophylaxis of thrombotic complications in patients after reconstructive
      operations on the main arteries of the lower extremities, made for
      arteriosclerosis obliterans in a critical ischemia stage].
AB  - Results of reconstructive operations, performed on the main arteries of the lower
      extremities (LE) in 63 patients, suffering obliterating atherosclerosis were
      analyzed with the objective to analyze the causes of thrombotic complications
      occurrence. There was established, that common clinical screening tests, applied
      for control of the hemostasis system state, do not permit completely to reveal
      thrombophylic changes in early postoperative period timely and to prevent the
      occurrence of the reconstructed segments thrombosis. Direct correlation
      connection between the ischemia stage of the LE tissues, the reperfusion changes
      signs and hyperaggregation severity, occurring due to deficiency of the blood
      serum natural anticoagulants in patients, suffering obliterating atherosclerosis,
      was established.

PMID- 24923113
TI  - [Changes of humoral immunity in patients operated for peritonitis].
AB  - The inflammation process course as well as probability of complications
      occurrence are determined by changes in humoral link of immunity. Positive
      dynamics of humoral component of the immune answer was trustworthy proved in
      patients, suffering local peritonitis, what have had witnessed the presence of an
      active and adequate function of the immune system, which was able to localize the
      inflammation process. In such course of the disease it is not necessary to
      conduct additional immune correction. Unfavourable immune profile and its
      dynamics in patients, suffering diffuse and spreaded peritonitis are determined
      by the quantity lowering of CD22 without its enhancement on the 3 - 7 day; low
      level of IgG in conjunction with high level of IgA and IgM (so called
      "scissors"), what do not change on the 3 - 7 day. The tendency of the IgG level
      lowering during the treatment constitute an urgent indication for the restorative
      therapy conduction, using immunoglobulins.

PMID- 24923114
TI  - [Reduction of the recurrences and postoperative complications in surgical
      treatment of hepatic echinococcosis].
AB  - Results of examination and treatment of 326 patients, suffering hepatic
      echinococcosis, in whom 449 surgical interventions were performed, were analyzed.
      In 123 of them the disease recurrence was diagnosed, and laparoscopic, laparotomy
      and puncture interventions were applied. Conduction of active screening
      examination of population in the regions, endemic for echinococcosis, application
      of effective intraoperative methods for prophylaxis of abdominal dissemination of
      invasive material, usage of antiparasitic chemical and thermal processing of
      cystic contents and its walls, left after echinococcectomy performance,
      postoperative prophylactic application of antiparasitic medicinal therapy have
      had permitted to lower the hepatic echinococcosis recurrence rate (down to 1.3%
      in last 5 yrs).

PMID- 24923115
TI  - [Sanation of biliary system using antiseptic decasan in complex treatment of
      cholangitis].
AB  - Experience of treatment of 17 patients, suffering cholangitis of various genesis,
      using antiseptic Decasan, is presented. Clinical efficacy of the preparation in
      complex treatment of cholangitis, confirmed by results of the bile
      bacteriological investigation, was noted.

PMID- 24923116
TI  - [Prognostication of efficacy of simultant laparoscopic operations in accordance
      to the risk estimation scale, and the method of establishing of indications and
      contraindications].
AB  - Experience of surgical treatment was summarized and its results were analyzed in
      patients, suffering biliary calculous disease, coexistent with other surgical
      diseases of abdominal organs. Main aspects of diagnosis and prognosis for
      efficacy of simultant operations were presented, and there were also adduced the
      method of prognosis of the operative treatment results in such patients, the
      proposed principle of determination of indications and contraindications for
      performance of simultant laparoscopic operations, a scale of the risk estimation
      for performance of such operative interventions.

PMID- 24923117
TI  - [Determination of the ulcer area in the diabetic foot syndrome using elaborated
      programe supply].
AB  - Efficacy of area estimation of the ulcer or the wound defect, using the programe
      apparatus system "WoundViewer", elaborated by specialists from Ukrainian
      scientific-practical centre and National technical university of Ukraine "KPI",
      was studied. The programe is based on objective estimation with a real scale
      viewing of the wound area and permit to measure area of wound, owing any form.
      The programe is highly effective during the process of dynamical estimation of
      the treatment quality.

PMID- 24923118
TI  - [Autoplasty of recurrent laryngeal nerve in the thyroid gland surgery].
AB  - Efficacy of autoplasty of recurrent laryngeal nerve (RLN) for laryngeal
      reinnervation in surgery of differentiated cancer of thyroid gland was studied.
      Prospectively 8 patients were examined, in whom laryngeal reinnervation, using
      the RLN autoplasty, for the abduction laryngeal paralysis was done. The
      examination was performed before and after the operation, it included
      videolaryngoscopy, acoustic analysis and the patient's self-estimation of
      psychosocial consequences of the voice-formation disturbance. Improvement of a
      vocal cords spacious positioning was noted in 38% patients, and was confirmed by
      trustworthy improvement of the voice-formating parameters after the operation,
      comparing with a preoperative state. In 72% patients the vocal aperture closure
      was incomplete and the voice-formation parameters trustworthy differed from such
      in patients of a control group. When the intact alternative nerves-donors for
      laryngeal reinnervation are present (distal stump of PLN, ipsilateral and
      contralateral main branch of cervical loop) the RLN autoplasty performance must
      be maximally postponed because of low efficacy of such method of surgical
      laryngeal reinnervation.

PMID- 24923119
TI  - [Conclusive pleuropulmonectomy in patients with pulmonary tuberculosis].
AB  - The results of performance of conclusive pleuropulmonectomy (CPPE) in 2004-2012
      yrs in 16 patients, suffering multiresistant pulmonary tuberculosis are
      presented. In 75% patients during the first operation the atypical (using
      apparatuses) pulmonary resection was performed. CPPE was done for fibrous
      cavernous tuberculosis in 11 (68.8%) patients, for cirrhotic tuberculosis - in 4
      (25.0%), caseous pneumonia - in 1 (6.3%). Intraoperative complications rate was
      12.5%. Early postoperative complications have had occurred in 5 (31.3%) patients,
      and the late - in 3 (18.8%). Total efficacy of CPPE have had constituted 81.3%.

PMID- 24923120
TI  - [Dynamics of inflammatory mediators and indices of antiendotoxic immunity in
      children with purulent-destructive pneumonia].
AB  - There were examined 220 children, in whom purulent-destructive pneumonia (PDP)
      was diagnosed. Level of anti-inflammatory mediators and indices of the
      antiendotoxine immunity was determined in the blood serum, using immunoassay
      analysis, after admittance to hospital. There was established, that in PDP in
      children the concentration of anti-inflammatory mediators interleucines (IL--1
      beta, IL-6) is enhanced, as well as of the tumor necrosis factor-- alpha (TNF
      alpha), C-reactive protein (CRP), while titre of antibodies to endotoxine class G
      lowers, and the level of lipopolisaccharid-binded protein (LBP) and soluble form
      of CD14 receptor (sCD14) is raised, not depending from the patient state
      severity.

PMID- 24923121
TI  - [Application of statistical models for prognostication of outcomes in injured
      persons with severe trauma].
AB  - Basing on data, concerning the injured persons state, the investigations results
      for elaboration and application of statistic models, prognosticating the trauma
      outcome, were analyzed. Selected information about 373 injured persons, who were
      treated in Traumatic Shock Department, is presented. There was established, that
      the statistical models elaborated is expedient to use together with other
      qualitative and quantitative methods of prognostic determination of outcome in
      severely injured persons.

PMID- 24923122
TI  - [Investigation of mechanical properties of materials used for functional
      stabilization in pilon fractures].
AB  - Existing methods of surgical treatment of the pilon fractures do not provide
      early functional rehabilitation of patients. The lack of confidence in secure
      fixation of fragments in significant quantity of patients causes necessity to
      apply a plaster immobilization during long time. While seeking possibilities of
      early functional treatment of the pilon fractures there was proposed a theory of
      "functional stabilization" (instead of "artificial", but necessary plaster
      immobilization), materials and technologies for its realization. For
      substantiating, from the biomechanical point of view, of expediency of a new
      materials (Softcost, Scotchcost) application the data about their physic-chemical
      properties were adduced, and in particular, there were studied the bowing values,
      depending on loading, and modules of elasticity of these materials.

PMID- 24923123
TI  - [Studying of cytokine dynamics in injured persons with severe burns for
      estimation of severity and prognosis].
AB  - Dynamics of a blood serum concentration of tumor necrosis factor-alpha (TNF-
      alpha), interleukines (IL-1beta, IL-10) in 35 patients, suffering severe burn,
      and possibility of application of these indices as biomarkers of the severity
      state and the complications prognosis, were studied. During the investigation
      there was established, that TNF-alpha concentration on the 8 - 10th and 19 - 21th
      day after trauma does the best for characterization of a burn total area, while
      the IL-1beta concentration on the 8 - 10th day after trauma - the deep affections
      severity and the IL-10 concentration on the 19 - 21th day after trauma - the deep
      affections severity. Hyperreactivity, caused by enhanced production of TNF-alpha,
      IL-1beta and IL-10, witnesses the raised risk of development of the organs
      complications. And adversely, hypo- and areactivity in extended and deep burns
      witnesses about enhanced risk of lethality. The blood serum concentration of TNF
      alpha, IL-1beta and IL-10 is expedient to use as a biomarkers of the patients
      state severity and for the course prognosis of pathological process.

PMID- 24923124
TI  - [New approaches to the treatment of a ligature fistulas].
AB  - Original method of treatment of a ligature fistulas was proposed, using the
      ligature taking out via fistular passway or doing the cutaneous cutting under
      continuous ultrasonographic control. The efficacy and safety of the method,
      comparing with existing methods (probing "blindly" and excision of the fistula),
      was estimated. Original method owes advantage of possibility to visualize the
      ligatures and instruments on all stages of the intervention, small need in
      anesthesia, good medical-statistical indices. The method proposed constitute a
      clinically beneficial intervention and more effective one.

PMID- 24923125
TI  - [Application of intravenous total anesthesia in "small" surgical interventions in
      children].
AB  - Results of operative treatment of 458 children, ageing 3 - 15 yrs, using various
      interventions with intravenous total anesthesia, were analyzed. Application of
      the anesthesia scheme proposed, consisting of propofol, ketamine and phentanyl
      combination, have had permitted to guarantee an adequate anesthesiological
      defense while performance of "small" operative interventions in children.

PMID- 24923126
TI  - [A model of inflammatory process in the abdominal cavity in experiment].
AB  - The model of chronic inflammatory process in abdominal cavity was elaborated in
      experiment on big laboratory animals. Intraoperatively in 12 laboratory pigs a
      chronic infiltrate was formatted between adducting and abducting intestinal loops
      with its mesenterium; in a region of gastroduodenal ligament and liver; between
      spleen and great omentum. Dynamics of the infiltrate formation was studied on the
      60th, 90th, 120th and 180th day in accordance to data of bacteriological and
      histological investigations. Application of the method proposed permits to create
      chronic infiltrate with prognosticated course, to reduce the experiment duration
      and quantity of experimental animals used.

PMID- 24923127
TI  - [Effect of cytokines and stromal cells of adipose tissue on integration of a two
      component composite net imlant into biological tissues].
AB  - Morphological changes in biological tissues, surrounding the composite net-like
      implant, owing large pores "Ultrapro", and also its combination with adipose
      transplant, fibrin, enriched with thrombocytes, were studied in experiment on 36
      adult male rats of a Wistar line. While application of such construction the
      processes of creation and organization of connective tissue, neoangiogenesis as
      well as development of a new adipose tissue are improved. As a consequence of
      increase of concentration of highly active biological substances and regenerative
      cytokines in combination of the net implant with adipose transplant, containing
      multipotent stem cells, proliferative activity of all cellular elements,
      surrounding the net implant, is raising, what predispose its optimal integration
      into surrounding tissues.

PMID- 24923128
TI  - [Pancreatic pseudocysts: diagnosis and treatment].

PMID- 24923129
TI  - [Mini-invasive interventions for biliary calculous disease complicated by acute
      cholangitis and mechanical jaundice].

PMID- 24923130
TI  - [Intracystic localization of gallbladder in a patient with acute calculous
      phlegmonous cholecystitis].

PMID- 24923131
TI  - [Posterior reversible encephalopathy syndrome following a liver transplantation
      from a living donor].

PMID- 24923132
TI  - From brain science to bookworms.

PMID- 24923134
TI  - Young children in the child welfare system: what factors contribute to trauma
      symptomology?

PMID- 24923135
TI  - The impact of prevention Programs on decisions in child protective services.

PMID- 24923133
TI  - A translational neuroscience perspective on the importance of reducing placement
      instability among foster children.

PMID- 24923136
TI  - The development of child protection supervisors in Northern British Columbia.
AB  - This research involved three different groups of employees in a provincial
      government organization responsible for the delivery of child welfare services
      throughout northern British Columbia. The research sought to understand the
      skills that are most important to supervision, how the skills can be developed,
      and the barriers that might impede this development.

PMID- 24923137
TI  - Parent representation model in child safety conferences.
AB  - Child welfare-involved parents are often isolated and lack support and skills to
      navigate complex systems. Programs using a parent representation service model in
      child protection can offer an exceptional and critical form of support and
      empowerment to birthparents, promote parental engagement and cooperation, and
      teach system navigation skills. While there is a notable emphasis on an overall
      family-centered and strength-based approach in child welfare, much progress is
      still needed in giving voice to parents, empowering them, including them in
      decisionmaking about the case, and seeking their cooperation. Funding should be
      directed to recruiting more parent representatives to assist birthparents in
      their communities as well to educating and training child protective services
      workers by transferring values and strategies implemented by parent
      representatives. Although additional research is certainly necessary, it appears
      that programs such as the Child Welfare Organizing Project in New York City may
      be an important step toward building partnerships with families impacted by the
      child welfare system in promoting child safety, well-being, and permanency.

PMID- 24923138
TI  - The bookworm club: the implementation story of an evidence-informed literacy
      program for children residing in out-of-home care in Ontario.

PMID- 24923139
TI  - [Prognostication of gastroduodenal ulcer course complicated by hemorrhage].
AB  - Dynamics of the blood serum level of serotonin in the patients, suffering
      gastroduodenal ulcer, Complicated by hemorrhage, was analyzed. The highest level
      of serotonin was observed in gastric ulcer, complicated by hemorrhage. These
      changes correlate with the blood loss severity enhancement, the achievement of a
      nonstable state of endoscopic hemostasis, high activity of inducible NO-synthase
      (iNOS) of periulcerative mucosa. The obtained data analysis permits to
      prognosticate the pathological process course and to improve the program of
      treatment.

PMID- 24923140
TI  - [Estimation of efficacy of the elaborated algorithm of differential diagnosis and
      treatment of acute mesenterial ischemia].
AB  - Clinical efficacy of the elaborated algorithm for differential diagnosis and
      treatment was studied, basing on analysis of the main diagnostic clinical
      features for presence of an acute mesenterial schemia (AMI), the concomitant
      diseases identification as the risk factors for the AMI occurrence, the results
      estimation of accessible noninvasive and invasive methods of diagnosis,
      correlation between the patient's survival indices and conservative and operative
      treatment, depending on the AMI stage and the patient state.

PMID- 24923141
TI  - [The choice of hernioplasty method in elderly and senile patients with
      noncomplicated inguinal hernia].
AB  - Complex examination and surgical treatment was performed in 220 elderly and
      senile patients for various types of inguinal hernia (IH) in accordance to Nyhus
      classification. In 103 patients (the main group) hernioplasty was performed
      according to Lichtenstein method or using modifications, proposed by us; in 117
      (the comparison group)--the tension hernioplasty, using the patient's tissues.
      According to data of morphological investigation of the inguinal channel musculo
      aponeurotic structures in 24 patients there was established, that in the oblique
      IH formation a biochemical instability of the connective tissue structures plays
      a leading role, while in a direct type of IH--the reduction of muscular fibrils
      quantity, lowering their elasticity and a contractile answer velocity.
      Application of a tension-free methods of plasty in elderly and senile patients is
      pathogenetically substantiated, it permits to reduce the hospital stay, the
      physical rehabilitation duration, the complications and recurrences rate, and to
      improve quality of life in remote follow-up period after operative intervention.

PMID- 24923142
TI  - [Femoral hernia in elderly and senile patients, peculiarities of surgical
      tactics].
AB  - The results of surgical treatment of 74 elderly and senile patients, suffering
      femoral hernia (FH), were analyzed. In 39 (52.7%) of them intestinal
      incarceration was noted. The most effective procedures have appeared those, which
      incorporate application of polypropylene implants for the femoral ring
      strengthening while hernioplasty performing in elderly and senile patients.
      Application of transabdominal preperitoneal endovideohemioplasty constitutes a
      perspective direction in surgical treatment of FH.

PMID- 24923143
TI  - [Application of ozonated perftoran in the treatment of spreaded peritonitis].
AB  - Results of surgical treatment of 114 patients, suffering spreaded peritonitis of
      various etkoogy, were analyzed. To patients of the comparison group basic
      conservative therapy was conducted. In patients of the main group was applied
      intravenous infusion of ozonated perftoran (OP) in 1 mg/kg dose, concentration of
      ozone 5 mg/l, solely or together with metabolic immunomodulator and detoxicator
      glutoxim. To all the patients the routine clinical investigations were conducted:
      in the blood erythrocytes there were measured concentration of diane conjugates,
      of malonic dialdehyde, activity of catalase, content of the middle molecular mass
      peptides in blood and urine, as well as of rest nitrogen, urea, creatinine,
      common bilirubin, state of the protein and electrolyte balance. Basing on
      analysis of results of the conducted investigations there was revealed, that
      combined, local and systematic, application of OP and glutoxim together with
      basic therapy in spreaded peritonitis is pathogenetically substantiated.

PMID- 24923144
TI  - [Multivariate analysis of risk factors of the anal functional disorders after
      abdominal-anal resection with delayed formation of colonic-anal anastomosis].
AB  - Multivariate analysis of clinical factors was conducted on the material histories
      of 195 patients treated between 2004 and 2006. In Donetsk regional antitumor
      center, which for rectal cancer (RC) is made abdomino-anal resection of the
      rectum with the delayed formation koloanal anastomosis after bringing down the
      colon to the perineum. In 97 patients the operation was performed with the use of
      electric welding soft tissue (EWST), in 98--a standard way. Studied the quality
      of life of patients using a questionnaire QLQ C30-CR38 and the function of the
      anal incontinence (Wexner scale). It is established, that the greatest influence
      on the function of the anal continence have a view of a combined and complex
      treatment, radicality intervention, the method of forming koloanal of
      anastomosis. Application EWST the second stage of surgery to cut off excess
      relegated intestine helped reduce the risk of poor function of the anal
      continence.

PMID- 24923145
TI  - [Use of antiseptic dekasan in complex treatment of peritonitis].
AB  - Experience in treatment of 91 patients with peritonitis on various genesis using
      antiseptic Dekasan are presented. A marked clinical efficacy compared with that
      of other antiseptics in the complex treatment of peritonitis was noted.

PMID- 24923146
TI  - [Complications after therapeutic dissection of the neck in the treatment of
      differentiated thyroid gland cancer].
AB  - There were analyzed retrospectively 1078 patients, operated on for differentiated
      cancer of thyroidal gland (DCTHG) in 2009-2012 yrs in the Centre, who have had
      following surgical complications: the injury of the X, XI, XII cranial nerves
      pairs, of the motor and sensitive branches of cervical and brachial plexuses,
      lymphorrhea, hypoparathyrosis and hematoma of the neck. In 868 patients the
      primary operations were performed, 304 - were operated for the recurrent forms.
      In 271 patients (the comparison group) thyroidectomy was performed, in 884 (the
      main group)--thyroidectomy and different kinds of the neck dissection, in 121-
      the operation was done, using neuromonitoring. Therapeutic dissection of the neck
      -the central and lateral one, as well as primary and repeated, may be performed
      relatively safely in patients, suffering DCTHG. In reoperations the rate of
      injury of the X, XI, XII cranial nerves pairs, of the motor and sensitive
      branches of cervical and brachial plexuses is increasing. Application of
      intraoperative electroneuromonitoring for identification of peripheral nerves
      permits to lower the neurotrauma occurrence.

PMID- 24923147
TI  - [Incidence of anaplastic tumor in structure of other histologic forms of the
      thyroid gland cancer].
AB  - The degrees of invasiveness, proliferative activity, morphofunctional activity of
      nuclei in the thyroidal gland tumors were studied, while analyzing material,
      obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated
      on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion
      of the tumor progression grade) and mitotic activity in cellular population were
      determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type
      of THGC is the most malignant one. There were determined a spindle-like, giant
      cell and squamous-cell forms of undifferentiated THGC. The presence of sites of
      differentiated cancer in 33% of histological preparations witnesses the
      interrelationship with the earlier existed pathological process.

PMID- 24923148
TI  - [The role of tumoral stroma in prognosis of course of luminal mammary gland
      cancer type A].
AB  - Peculiarities of tumoral stroma, the indices of overall survival (OS) and disease
      free survival (DFS) were studied up in patients, suffering luminal mammarial
      gland cancer MGC type A. If the stroma have had occupied more than 50% of the
      tumor square, the OS and DFS indices were the highest. The link was established
      between the OS and DFS indices, the stromal square and expression of the MGC
      cells toward the estrogen and progesterone receptors. The pronounced stromal
      reaction was connected with the OS index improvement even in a less pronounced
      expression to estrogen and progesterone.

PMID- 24923149
TI  - [Modern algorithms of diagnosis of benign tumors of the mammary gland: the role
      of molecular-genetic methods].
AB  - Experience of treatment in 2010-2012 yrs of the patients, suffering mammarial
      gland tumors, in The Center of Reconstructive and Restoration Medicine (The
      University Clinic) of The Odessa National Medical University was analyzed. There
      were examined 143 women with morphologically confirmed mammarial gland cancer
      (MGT), 56--benign mammary gland tumors and 50 healthy women. Molecular-genetic
      investigation was performed in the patients-women: there were determined the gene
      C634G polymorphism of VEGF and of the gene G308A of TNF--a with subsequent
      estimation of correlation of the mutations quantity and the mammarial gland
      diseases rate. Algorithm of differential diagnosis of benign tumors must include
      estimation of polymorphism of the VEGF gene C634G. While revealing of the
      heterozygous or homozygous bearers of mutation with the gene C634G polymorphism
      of VEGF the risk of the MGC occurrence is enhancing, what may serve as additional
      criterion for expedience for conduction of operative treatment in such patients.

PMID- 24923150
TI  - [Correlation of clinico-neurological peculiarities and morphological signs of
      small hernias (protrusion) of the lumbar intervertebral discs in formation of
      discogenic pain syndromes in patients of different age].
AB  - Morphological signs of small hernias (protrusion) of intervertebral discs (IVD),
      the results of a neurovisualizing methods of investigation and clinico
      neurological features of osteochondrosis as well, were summarized. In young and
      middle age patients morphological chatacteristics of small hernias (protrusion)
      of IVD, data of neurovisualizing methods of investigation have had correlated
      with clinico-neurological features of the disease and were the key determinants
      while performance of the puncture laser microdiscectomy. In a middle age and
      elderly patients a weak correlation was noted between the IVD protrusion
      dimensions and intensity of a lumbar and radicular pain syndromes, functional
      activity (Osvestry index), what have had permitted to apply a pathogenetically
      substantiated method of a durable epidural pharmacotherapy. The investigation
      results witness the necessity of differentiated application of the puncture
      methods of treatment for the pain discogenic syndromes in patients of different
      age.

PMID- 24923151
TI  - [Anesthesiological support during nephrectomy in living related donors].
AB  - International demands exist for the patients safety guaranteeng, in the live
      donors of organs peculiarly, who consciously agreed to be operated on with the
      organ excision for the patient sake. That's why it is important to elaborate
      optimal measures of safety for such operative intervention, including
      anesthesiological support for donors of kidney. Advantages of modern anesthetics
      application, ingalation introduction of sevofluran and intravenous injection of
      propophol over standard analgesia were discussed. The investigation was conducted
      in 53 live familial donors of kidney. Application of the recommended tactics have
      permitted to reduce the risk of occurrence and rate of complications in these
      patients.

PMID- 24923152
TI  - [Transperitoneal and transvaginal hysterectomy using devices of the dosed high
      frequency electrical current].
AB  - The experience of application of apparatuses of the dosed high-frequency electric
      influence EK300M-1 "Patonmed" and energetic platform "Forcetriad", manufactured
      by Valleylab firm, during hysterectomy performance, using various surgical
      accesses, was presented. The variants of the applied regimens, depending on the
      vessels diameter and coexistant diseases, were proposed.

PMID- 24923153
TI  - [Anaerobic nonclostridial infection of pelvis: classification and its practical
      application].
AB  - Anaerobic nonclostridial infection of pelvis are analysed in 89 patients that
      were on treatment in the department of festering surgery in 1999-2012 years.
      Clinical classification of disease is offered and it is applied in practice for
      dividing of research array into clinically-morphological groups with the aim of
      the differentiated going near a surgical treatment.

PMID- 24923154
TI  - [The choice of optimal method of the closure of soft tissue defects in the deep
      injuries of the extremities].
AB  - Comparative analysis of the treatment results in 52 patients, suffering deep
      defects of the coverage tissues of extremities, was done, basing on applying of
      flaps with temporary and constant nutrent pedicle. The extremity functional state
      and the patient's quality of life were determined, using SF-36 and EUROQOL-5D
      questionnaire. The method of plasty, using the flap on a constant nutrient
      pedicle, have appeared the optimal one for closure of defects in the coverage
      tissues of the extremities.

PMID- 24923155
TI  - [Immediate and long-term results of surgical treatment of patients for traumatic
      mandibular fracture].
AB  - The analysis of immediate and long-term results of the surgical treatment of 286
      patients, operated for traumatic mandibular fractures in the Department of Oral
      and Maxillofacial Surgery, National O. O. Bogomolets Medical University. In 67%
      of patients the anatomical shape of the bone was adequately restored. The
      presence of residual displacements in other cases was determined by the fracture
      type and localization, the technical complexity of the surgical intervention,
      lack of fixation rigidity under certain functional load conditions. In long terms
      of observation the infection and inflammatory complications were observed in
      13.4% of patients, delayed unition and non-unition of bone fragments occurred--in
      4.7%, arthosis with persistent dysfunction of the temporomandibular joint--in
      6.7%, fibrous ankylosis--in 1.3%. Secondary displacement of fragments was
      observed in 23.5% of patients due to insufficient stiffness and reliaability of
      the bone-fixatorsystem. The non-precise reposition of fragments and secondary
      displacements in the early and late postoperative period were the main cause of
      occlusal disturbances of various severities, noted in 28% of operated patients,
      limitation of mouth opening (10%), TMJ disorders and changes in masticatory
      stereotype (33%), the sensation of pain and discomfort in tough food chewing
      (35%). A statistical analysis of the effectiveness of different osteosynthesis
      methods depending on the type and localization of the fracture was carried out
      and recommendations for usage of fixation devices in clinical practice were
      given.

PMID- 24923156
TI  - [Pathomorphological peculiarities of hemomicrocirculatory bed of the small and
      large intestine in acute peritonitis].
AB  - Experimental comparative morphological investigation of hemomicrocirculation bed
      (HMCB) of the small and large bowel wall was performed in dynamics of an acute
      serous peritonitis. Spreaded aseptic peritonitis was simulated using injection of
      5 ml of gamma-caraginen (Sigma, USA) in 1 ml of isotonic solution of sodium
      chloride. On the early stage of peritonitis (in 12 h from beginning of the
      experiment) in mucosa of small bowel nonsignificant venuls dilatation and the
      capillary lumen reduction were observed. In 1 day (reactive stage of peritonitis)
      in mucosa the quantity of capillars have had reduced significantly, comparing
      with such observed previously. On the 2-nd day (toxic stage of peritonitis) some
      capillary dilatation in intestinal villi and crypts coexistant with the blood
      rheology disorders in a form of stasis, change in permeability of the vessels
      walls, predominantly of the venous, was noted. On the 3-d day (late stage) the
      arteriol's spasm have had reduced, capillary paralytic dilatation was revealed.
      The staged course of experimental peritonitis with the HMCB changes,
      characteristic for every stage, was confirmed, basing on analysis of the
      investigation result.

PMID- 24923157
TI  - [Physical methods to determine compatibility of implants].
AB  - The effect of the living organism on the polymer materials used for the
      manufacture of grids for implants. It is shown that the recipient's body is
      actively working to exogenous material , destroying its surface layer and forms
      around the implant insulating fibro-connective tissue capsule, the thickness of
      which depends on the severity of the organism's reaction to a foreign body.
      Proposed instrumental method of determining compatibility before surgery implant
      material with the recipient using an atomic force microscope (AFM).

PMID- 24923158
TI  - [Trocar hernias: etiology, treatment, prophylaxis].

PMID- 24923159
TI  - [The external ear reconstruction using prelaminated flap in combination with the
      tissue expression].

PMID- 24923160
TI  - [Incarcerated postoperative hernia of the abdominal wall evolved after
      laparoscopic cholecystectomy].

PMID- 24923161
TI  - [Observation of medicinal granuloma of the soft tissues].

PMID- 24923162
TI  - [Complete genome phylogenetic analysis of five H9N2 avian influenza viruses
      isolated from poultry flocks in Qinghai lake region].
AB  - Five H9N2 avian influenza virus strains were isolated from the environmental
      samples in live poultry market in Qinghai Lake region from July to September,
      2012. To evaluate the phylogenetic characteristics of these H9N2 isolates, the
      eight gene segments were amplified by RT-PCR and sequenced. The phylogenetic and
      molecular characteristics of the five strains were analyzed. The results showed
      that the HA genes of five strains shared 93. 2%-99. 1% nucleotide identities with
      each other, and the NA genes shared 94. 5%-99. 8% nucleotide identities. The HA
      cleavage site sequence of the A/environment/qinghai/ 017/2012 isolate was
      PSKSSRGLF, and the HA cleavage site sequences of the other four strains were all
      PSRSSRGLF. The HA receptor-binding site had the Q226L mutation. The M1 gene
      segment had the N30D and T215A mutations. The phylogenetic analysis showed that
      the five strains were similar to the virus A/chicken/Hunan/5260/2005 (H9N2)
      isolated in Hunan Province, China and were reassortant genotype viruses; the HA,
      NA, and NS genes belonged to the Y280-like lineage; the MP gene belonged to the
      G1-like lineage; the NP, PB1, PB2, and PA genes belonged to the F98-like lineage.

PMID- 24923165
TI  - [Genetic characteristics of hemagglutinin in measles viruses isolated in Henan
      Province, China].
AB  - This study aims to investigate the genetic characteristics of hemagglutinin in
      wild-type measles viruses in Henan Province, China and to provide a basis for
      measles control and elimination. Specimens were collected from suspected measles
      cases in Henan during 2008-2012. Cell culture was performed for virus isolation,
      and RT-PCR was used to amplify hemagglutinin gene. The PCR products were
      sequenced and analyzed, including construction of phylogenetic tree and analysis
      of the distance between the isolated virus and the reference virus; then, the
      variations in predicted amino acids were analyzed. The results showed that 12
      measles viruses were isolated in Henan Province and identified as H1a genotype;
      the nucleotide and amino acid homologies were 98.0%-100% and 97.2%-99.8%,
      respectively. One glycosylation site changed in all the 12 sequences because of
      the amino acid mutation from serine to asparagine at the 240th site, as compared
      with Edmonston-wt. USA/54/A. Overall, the wild-type measles virus genotype
      circulating in Henan Province from 2008 to 2012 was H1a, with high homology
      between strains; there were some variations in amino acid sequences, resulting in
      glycosylation site deletion.

PMID- 24923164
TI  - [Establishment and primary application of a novel resequencing pathogen
      microarray-based assay for detecting pathogens in patients with unexplained
      diarrhea].
AB  - In this study, a novel resequencing pathogen microarray (RPM)-based multi
      pathogen detection assay was developed to simultaneously detect 14 rotaviruses, 7
      caliciviruses, 8 astroviruses, 28 enteroviruses, and 16 rare diarrhea viruses in
      patients with diarrhea syndrome. The specificity of the assay was examined using
      confirmed virus-positive specimens, and the sensitivity was evaluated by serial
      ten-fold dilutions of in vitro transcribed RNA. RPM assay could detect and
      differentiate virus types/subtypes at 20-2000 copies/microL. The detection
      threshold of RPM was determined by adjusting the reference concentration, and the
      detection steps were optimized to type Enterovirus. The nucleic acids of 10 stool
      samples from patients with unexplained diarrhea were screened, and 6 of them
      showed positive results. The RPM results were further verified by singleplex PCR
      followed by sequencing, and no difference was found between the two assays. In
      conclusion, we have established a high-throughput RPM assay with high specificity
      and sensitivity, which demonstrates a great potential for the identification of
      pathogens in patients with unexplained diarrhea and the management of emerging
      epidemic.

PMID- 24923166
TI  - [Molecular epidemiological characteristics of HIV-1 strains isolated from newly
      diagnosed MSM subjects (2006-2010) in Beijing, China].
AB  - This study aims to analyze the molecular epidemiological characteristics of HIV-1
      strains prevailing among men who have sex with men (MSM) in Beijing, China. The
      pol gene fragments from 250 newly diagnosed HIV-1-infected MSM individuals during
      2006-2010 in Beijing were amplified by RT-nested PCR, sequenced, and
      phylogenetically analyzed. HIV-1 pol gene from 189 individuals were amplified and
      analyzed; 81 (42. 9%), 3 (1. 6%), 2 (1.0%), 88 (46. 6%), and 15 (7.9%)
      individuals were infected with HIV-1 subtypes B, B', C, CRF01_AE, and CRF07_BC,
      respectively. The subtypes B and CRF01_AE could both be grouped into two
      clusters, and CRFO7_BC strains shared high homology and were presumed to
      originate from a common ancestor. The HIV-1 circulating in MSM in Beijing had a
      lower genetic diversity than in heterosexuals. The HIV-1 epidemic (2006-2010) in
      MSM in Beijing was actually a rapid spread of HIV-1 CRF01 AE and B, or rather
      native strains of the two viruses.

PMID- 24923167
TI  - [Genetic characterization of echovirus 6 isolated from meningitis and
      encephalitis cases in Shandong Province, China].
AB  - To analyze the genetic characteristics of echovirus 6 (E6) isolated from
      meningitis and encephalitis cases in Shandong Province, China, we collected
      cerebrospinal fluid samples from meningitis and encephalitis cases in Shandong
      Province from 2007 to 2012 for virus isolation. Viral RNAs were extracted from
      positive isolates, and complete VP1 coding regions were amplified by RT-PCR and
      sequenced. Homology comparison and phylogenetic analysis were performed. Six
      isolates were identified as E6 by microneutralization assay and molecular typing.
      The homology analysis showed that the six isolates had 78. 6%-99. 8% nucleotide
      and 95. 5%-100. 0% amino acid identities with each other, as well as 76. 9%-78.
      4% nucleotide and 92. 3%-95. 1% amino acid identities with the prototype strain
      (D' Amori). The phylogenetic analysis based on the integrated VP1 sequences
      indicated that all Shandong E6 isolates could be separated into four clusters,
      designated as A, B, C, and D. The six E6 isolates belonged to clusters A, B, and
      D. Our study reveals high genetic differences between Shandong E6 isolates and
      suggests different transmission lineages of E6 co-circulated in Shandong
      Province.

PMID- 24923168
TI  - [The association between polyomaviruses JC infection and gynecologic tumors].
AB  - The JC virus is a widely infected human polyomavirus. Recent foreign researches
      showed that the JC virus infection is correlated with tumors of nervous system
      and digestive system, while, and study on the relationship between JC virus
      infection and gynecological tumor is seldom reported. In this study, we first
      establish the nucleic acid detection methods and procedures for JC virus and its
      highly homologous BK virus. The JC and BK viruses infection was evaluated by
      detect the viral DNA in samples including biopsy tissues, serum as well as urine
      of myoma of uterus (98 cases), cervical cancer (84 cases), endometrial cancer (40
      cases) and ovarian tumor (72 cases) patients. The BK viral DNA positive rate was
      significantly higher in urine samples than that of blood and biopsy samples, and
      there is no significant difference of the BK viral DNA positive rate among all
      patient groups. The JC viral DNA positive rate is almost 0 in serum samples and
      biopsy. tissues, however, viral DNA positive rate is more than 50% in urine
      samples. In fibroids group, the JC viral DNA positive rate is up to 65. 3% which
      is significantly higher than that in other patients groups and healthy control.
      Further gynecological tumor associated viruses detection showed that only human
      papilloma virus infection is associated with cervical cancer, the herpes simplex
      virus, EB virus and cytomegalovirus infection is extremely low in our patient
      groups. No synergistic effect on gynecological tumor caused by viruses co
      infection was observed. Our study showed that JC virus infection is highly
      related to the pathogenesis of uterine fibroids.

PMID- 24923169
TI  - [Morphogenetic study of human adenovirus type 41 in 293TE cells].
AB  - To investigate the morphogenetic process of human adenovirus type 41 (HAdV-41),
      293TE cells were infected with purified wild-type HAdV-41, and ultrathin sections
      of infected cells were prepared and observed under a transmission electron
      microscope. Results showed that HAdV-41 entered host cells mainly through three
      ways: non-clathrin-coated pit, clathrin-coated pit, and direct penetration of
      plasma membrane. In addition, cell microvilli might help HAdV-41 enter cells.
      After entering into cells, HAdV-41 virus particles could be found in vacuoles or
      lysosomes or be in a free state in cytoplasm. Only free virus particles could be
      found near nuclear pores (NP), suggesting that the virus needed to escape from
      lysosomes for effective infection and viral nucleoprotein entered the nucleus
      through NP. Progeny viruses were as-sembled in the nucleus. Three types of
      inclusion bodies, which were termed as fibrillous inclusion body, condense
      inclusion body, and stripped condense inclusion body, were involved in HAdV-41
      morphogenesis. In the late phase of viral replication, the membrane integrity of
      the infected cells was lost and viral particles were released extracellularly.
      This study reveals the partial process of HAdV-41 morphogenesis and provides more
      biological information on HAdV-41.

PMID- 24923170
TI  - [Genotypes and serotypes of avian infectious bronchitis viruses isolated during
      2009-2011 in Guangxi, China].
AB  - In order to investigate the prevalence and track genetic and antigenic evolutions
      of infectious bronchitis virus (IBV) and their prevalence in Guangxi, China since
      1985, gene amplification and sequencing and virus neutralization (VN) test on
      chicken embryo tracheal organ cultures were used in genotyping and serotyping of
      28 IBV isolates during 2009-2011 in Guangxi. The results of N gene sequencing and
      comparison showed that the 28 isolates and reference strains were classified into
      three groups, and most isolates belonged to group Ill, while the isolates in 1985
      2008 belonged to groups IV and II. The data of VN test indicated that the 28
      isolates belonged to 6 serotypes; among them, 71. 4% belonged to serotypes 1, 2,
      and 3, and 11 (39.3%) shared the same serotype with the current vaccine strains.
      Given the data of our previous study, it is found that prevalent serotypes and
      their proportions varied in different areas of Guangxi and during different
      periods. These data lay a good foundation for developing an oil-emulsified
      inactivated polyvalent vaccine containing local dominant serotypes for the
      effective prevention and control of infectious bronchitis.

PMID- 24923171
TI  - [Value of CODEHOP RT-pCR in detection of Flavivirus].
AB  - This study aims to analyse the value of CODEHOP RT-PCR in the detection of
      Flavivirus. According to the amino acid sequences of polyproteins of different
      flaviviruses published in GenBank, a pair of primers was designed using the
      CODEHOP method. One-step RT-PCR was used to detect Japanese encephalitis virus
      strain JEV1201, Dengue virus strain JKD001, and yellow fever virus vaccine
      YV6161. BLAST analysis and phylogenetic analysis were performed after the RT-PCR
      products of nucleocapsid genes were sequenced. The results showed that this
      method could amplify Flavivirus specifically, and the size and sequence of the
      target fragment accorded with the anticipated result. JEV1201 had the highest
      homology to Japanese encephalitis virus strain YL2009-4/YC2009-3, belonging to
      the branch of the phylogenetic tree of Japanese encephalitis virus strains.
      JKD001 had the highest homology to Dengue virus strain DENV-2/ID/1022DN/1975,
      belonging to the branch of the phylogenetic tree of Dengue virus strains. YV6161
      had the highest homology to Yellow fever virus strain 17D, belonging to the
      branch of the phylogenetic tree of Yellow fever virus strains. In conclusion, the
      method of CODEHOP RT-PCR can be effectively used to detect, identify, and
      phylogenetically analyse Flavivirus.

PMID- 24923172
TI  - [Study on challenge dose of pigeon paramyxovirus type 1 (Chuansha strain)].
AB  - In order to determine the challenge dose of pigeon paramyxovirus type 1 (PPMV-1)
      inactivated vaccine (S-1 strain). The virus titer of PPMV-1 E5 allantoic fluid
      (Chuansha strain) was determined using SPF chicken embryos in this research.
      After inoculating 30-day-old and 120-day-old pigeons with low-HI antibody against
      PPMV-1 (HI antibody < or =2) with different doses of PPMV-1 (Chuansha strain),
      the clinical symptoms and histopathological lesions of the challenged pigeons
      were examined. The results showed that the minimal lethal dose (MLD) of PPMV-1
      (Chuansha strain) was 102.5 ELD50, so we determined that 10(5.5) ELD50, which was
      1000 times the MLD, could be taken as the challenge dose in the vaccine efficacy
      test for PPMV-1 inactivated vaccine (S-1 strain).

PMID- 24923173
TI  - [Research progress in human enterovirus recombination].
AB  - Complex genetic variation has been known to occur during the transmission of
      human enterovirus (HEV), and the HEV virulence and pathogenicity enhanced by
      genetic recombination also pose a serious threat to human health. In recent
      years, the interest in recombination mechanism of genetic plasticity has been
      renewed with the emergence of pathogenic recombinant circulating vaccine-derived
      polioviruses, which were implicated in poliomyelitis outbreaks in several regions
      of the world with insufficient vaccination coverage. This paper reviews recent
      research progress in HEV genome, including evolutionary characteristics,
      recombination types, and in vitro recombinant construction.

PMID- 24923163
TI  - [Whole genome analysis of human group A rotavirus G9p[8] strains in Hebei lulong
      region, 2009-2011].
AB  - Abstract:This study aims to investigate the genetic characteristics of group A
      rotavirus (GARV) G9P[8] strains from infantile diarrhea samples in Hebei Lulong
      region from 2009 to 2011. We randomly selected five GARV G9P[8] strains in Hebei
      Lulong region from 2009 to 2011, amplified the 11 gene fragments of GARVs by RT
      PCR, and analyz their full-genome sequences by homology and phylogenetic analysis
      with DNAStar and MEGA. The nucleotide homology between strains LL11131077 and
      LL11131083 in 2011 was significantly higher than hat etween them and the other
      three strains in 2009 and 2010. The G9P[8] GARVs circulating in Hebei Lulong
      region from 2009 to 2011 elenged to the same genotype as the prevalent G9P[8]
      GARVs in other parts of the world. However,the two strains in 2011, compared with
      those in 2009 and 2010, were located in a different sub-branch of the
      phylogenetic tree and had amino acid mutations at many sites.

PMID- 24923174
TI  - [Research progress in mechanisms of cellular entry of Japanese encephalitis
      virus].
AB  - Japanese encephalitis virus (JEV) is a pathogenic mosquito-borne flavivirus which
      is responsible for outbreaks of severe viral encephalitis. The cellular entry of
      JEV is a prerequisite for Japanese encephalitis, so the understanding of its
      underlying mechanisms will provide more approaches for treating such disease. In
      recent years, increasing research has been conducted to investigate the
      mechanisms of cellular entry of JEV, and the results of research on other
      flavivirus have expanded the research directions for JEV. More methods will be
      used to suppress JEV infection because of the development of E protein antibodies
      and the discovery of several inhibitors of the cellular entry process. This
      review will summarize the recent advances in the mechanisms of JEV cellular entry
      and membrane fusion.

PMID- 24923175
TI  - [Research progress in human adenovirus].
AB  - Human adenovirus (HAdV) is one of the most important pathogens in infants and
      young children with acute respiratory infections and other diseases. This article
      reviews the literature on HAdV, including its molecular biological
      characteristics, detection and typing, and pathogenic mechanism, the clinical
      features and epidemiological characteristics of HAdV-related diseases, and the
      prevention and control of HAdV infections. So far, 67 types of HAdV have been
      identified, including recombinant variants discovered in recent years. The major
      epidemic strains that cause acute respiratory infections are HAdV-3 and HAdV-7,
      both of which belong to the subgroup B. HAdV often leads to acute respiratory
      infections, but it also causes diseases of other systems. HAdV-related diseases
      have similar clinical manifestations as those caused by other respiratory
      viruses, but often accompanied by gastrointestinal symptoms. The pathogenic
      mechanism of HAdV remains unclear, especially for the new recombinant variants,
      due to few studies on their association with diseases. Because there are no
      prospective, large randomized controlled trials of HAdV infections, the treatment
      of HAdV infections is controversial. Vaccine is the most effective measure to
      reduce respiratory HAdV infections, but it is still not commercially available.

PMID- 24923176
TI  - [Research progress in roles of high-risk human papillomavirus E2 protein].
AB  - High-risk human papillomavirus (HPV) is the principal cause of various cancers
      including cervical cancer, anal cancer, vulvar cancer, and some head and neck
      cancers. In the viral life cycle, by interacting with both viral and host DNA and
      proteins, the HPV E2 protein plays a pivotal role in viral transcriptional
      regulation and DNA replication, and it is also associated with modification of
      various cellular processes, including host gene transcription, RNA processing,
      apoptosis, ubiquitination, and intracellular trafficking, to create a convenient
      environment for a replicative cycle of the virus and contribute to the HPV
      pathogenesis. Elucidating the roles of E2 protein throughout the viral life cycle
      will improve our understanding of the viral life cycle and pathogenesis and help
      us identify novel antiviral agents with therapeutic potential. This article
      reviews the research progress in the structure, roles, and activity of high-risk
      HPV E2 protein, particularly that of HPV-16.

PMID- 24923177
TI  - [Research advances in herpesviruses glycoprotein N gene and its encoded protein].
AB  - Glycoprotein N is encoded by glycoprotein N (gN) gene of herpesviruses. The amino
      acid composition and expression level of this protein vary among difference
      species of herpesviruses. According to present studies, gN protein is expressed
      in cytoplasm of host cells, mainly in endoplasmic reticulum. The gN forms a
      complex with glycoprotein M in host cells. The complex is involved in the
      processes of viral replication and inter-cellular infection. Moreover, this
      protein plays a role in immune evasion from host immune system. The study will
      provide a theoretical basis for further study of herpesvirus gN gene and its
      encoded protein.

PMID- 24923178
TI  - [Advances in reverse genetics-based vaccines of foot and mouth disease].
AB  - Reverse-genetic engineering of foot and mouth disease virus (FMDV) can improve
      the productivity, antigen matching, antigen stability, immune response ability,
      and biological safety of vaccines, so vaccine candidates with anticipated
      biological characteristics can be promptly achieved. Negative influence in taming
      of virulent strains can also be decreased or avoided. Reverse genetics not only
      make up for deficiencies like limitation of viral nature, low success rate, and
      time and energy consuming, but also realize more active designing of vaccines.
      Therefore, reverse genetics is significant in improving integral quality and
      efficiency of vaccines. In this review, we use FMDV vaccines as an example to
      summarize improvement in biological characteristics of virulent strains and
      provide a reference for related researches.

PMID- 24923179
TI  - Deep-water anoxygenic photosythesis in a ferruginous chemocline.
AB  - Ferruginous Lake Matano, Indonesia hosts one of the deepest anoxygenic
      photosynthetic communities on Earth. This community is dominated by low-light
      adapted, BChl e-synthesizing green sulfur bacteria (GSB), which comprise ~25% of
      the microbial community immediately below the oxic-anoxic boundary (OAB; 115-120
      m in 2010). The size of this community is dependent on the mixing regime within
      the lake and the depth of the OAB-at ~117 m, the GSB live near their low-light
      limit. Slow growth and C-fixation rates suggest that the Lake Matano GSB can be
      supported by sulfide even though it only accumulates to scarcely detectable (low
      MUm to nm) concentrations. A model laboratory strain (Chlorobaculum tepidum) is
      indeed able to access HS- for oxidation at nm concentrations. Furthermore, the
      GSB in Lake Matano possess a full complement of S-oxidizing genes. Together, this
      physiological and genetic information suggests that deep-water GSB can be
      supported by a S-cycle, even under ferruginous conditions. The constraints we
      place on the metabolic capacity and physiology of GSB have important
      geobiological implications. Biomarkers diagnostic of GSB would be a good proxy
      for anoxic conditions but could not discriminate between euxinic and ferruginous
      states, and though GSB biomarkers could indicate a substantial GSB community,
      such a community may exist with very little metabolic activity. The light
      requirements of GSB indicate that at light levels comparable to those in the OAB
      of Lake Matano or the Black Sea, GSB would have contributed little to global
      ocean primary production, nutrient cycling, and banded iron formation (BIF)
      deposition in the Precambrian. Before the proliferation of oxygenic
      photosynthesis, shallower OABs and lower light absorption in the ocean's surface
      waters would have permitted greater light availability to GSB, potentially
      leading to a greater role for GSB in global biogeochemical cycles.

PMID- 24923180
TI  - Aspects of "fear" in Japanese quail chicks (coturnix coturnix Japonica)
      genetically selected for different levels of locomotor activity.
AB  - Domestic chicks selected for high and low locomotor activity in a novel
      environment have low and high levels of fearfulness, respectively. Using four
      commonly employed methods of estimating fear, namely emergence, open-field,
      response to a bell and tonic immobility tests, we found a similar effect in lines
      of Japanese quail selected for high and low locomotor activity, i.e. the active
      line appeared the least fearful. The present findings demonstrate that this
      effect is common to two gallinaceous species and two selection procedures. 

PMID- 24923181
TI  - Plumage phenotypes and mating preferences in Japanese quail.
AB  - A series of trials was conducted to study the relationship of plumage phenotype
      with choice of mate. Males which exhibited preferences tended to choose either
      females of their own kind, those of a plumage color with which they had prior
      experience, or those of the darker hue in a choice situation. Wild-type males
      which had no prior experience with albino females, tended to avoid albinos in
      preference to wild-type hens. This preference persisted when the head and neck
      plumage of albinos was dyed black, but when the body plumage of the albinos was
      dyed black, wild-type males did not exhibit a preference between them and wild
      type females. The data suggest that body plumage color is a factor in the male
      choice of females. 

PMID- 24923182
TI  - Daily patterns of courtship and mating behavior in the male Japanese quail.
AB  - Crowing behavior was monitored constantly in male Japanese quail housed singly
      over 30 successive days. The photoperiod was 16h of light and 8 h of dark. A
      daily pattern in crowing was observed in which the frequencies were elevated in
      the afternoon and at the beginning of darkness. However, peak crowing occured 2 h
      prior to the onset of light. These rhythms were highly correlated among
      individuals and extremely repeatable over the sequential days of observation. In
      a second experiment, males which were paired with females were observed for
      frequencies of crowing, courtship, and mating behavior during the lighted portion
      of the day. In this experiment, the same photoperiod (16L:8D) was maintained.
      Paired males exhibited a daily pattern in crowing similar to that observed in the
      singly housed males. The frequency of mating was the highest between 1200 and
      1300 h and lowest at 1400 h. Mating success was highest at midday, as were the
      number of males exhibiting mating behavior. These diurnal patterns in sexual
      behavior may depend on environmental cues such as photoperiod, which, in turn,
      may stimulate endocrine triggers. 

PMID- 24923183
TI  - Learning of submissive behavior in mice: A new model.
AB  - The experience of winning or loosing fights plays an important role in subsequent
      aggressive or submissive behaviors. In this study agonistic behavior of male mice
      was chosen to investigate learning mechanisms in the context of a biologically
      meaningful situation. An ICR mouse introduced into a group of five C57BL/6 mice
      was attacked by mice of high social status (Fighter, F), but not by lower ranking
      animals (Non-Fighter, NF). On this basis the following model was developed to
      study learning of submissive behavior. Day 1 (baseline trial): An ICR mouse was
      introduced to a single NF-C57 mouse. Few submissive behaviors (crouch) were
      observed in naive ICR mice upon contact with NF-C57 mice. Day 2 (learning trial):
      The same ICR mouse was defeated by an F-C57 mouse until it showed defensive
      upright posture upon approach. This criterion was reached after a mean latency of
      3.5 min and after being exposed to a mean number of 14 bites. Day 3 (retest
      trial): The same pairs as on day 1 confronted each other. Without being attacked,
      the ICR mouse showed a significant increase of submissive behavior (crouch,
      defensive sideways and upright) upon mere contact with the NF-C57 mouse when
      compared to day 1 and to control mice on day 3. Controls, confronted on all three
      days with NF-C57 mice, showed no increase in submissive behaviors. The results
      are discussed in terms of acquisition, memory, retrieval and extinction of
      learned submissive behavior. It is suggested that the mechanisms underlying
      learning of submissive behavior include generalization of conditioning and
      specific extinction processes. The further use of the learning scheme to assess
      drug effects is illustrated. 

PMID- 24923184
TI  - Attraction of adult tribolium confusum to flour conditioned by male conspecifics.
AB  - Adult Tribolium confusum, deprived of food for 6 days, were confronted with (1) a
      choice between fresh flour and flour conditioned by male conspecifics and (2) a
      choice between fresh flour and flour conditioned by female conspecifics. Both
      sexes, whether in mixed groups or in unisexual groups, preferred flour
      conditioned by males to fresh flour but showed no preference between fresh flour
      and flour conditioned by females. It was shown that there is an olfactory basis
      for the attraction of adult T. confusum to flour conditioned by male
      conspecifics, suggesting that a male-produced pheromone is involved. 

PMID- 24923185
TI  - Cardiac response of domestic chickens to hawk and goose models.
AB  - The response of precocial birds to configurational stimuli has been a source of
      controversy for decades. In this experiment we measured cardiac response of
      domestic chicks to "hawk" and "goose" silhouettes. The chicks' heart rates varied
      more in response to the hawk model than to the goose model, suggesting that the
      hawk silhouette is a more fearful stimulus than that of the goose. Our data
      document the recognition of a configurational stimulus without prior, pertinent
      experience. 

PMID- 24923186
TI  - Open-field behavior in guinea pigs: Developmental and adaptive considerations.
AB  - Two experiments were conducted with guinea pigs to test implications of a model
      which holds that social reinstatement tendencies and attempts to evade predation
      are the primary factors influencing how organisms initially react when placed in
      an open field. Because of the age-related reduction in need for maternal care,
      vocalization and ambulation latencies increased with age, and in support of the
      hypothesis that humans are perceived as predators, subjects tested in the
      presence of a human observer were less likely to move or vocalize than those
      tested alone. The data on vocalization latencies strongly suggest that the
      species- specific "whistle" of guinea pigs is a functional mammalian analog to
      the so-called "distress call" of domestic fowl. 

PMID- 24923191
TI  - Leptin and cardiometabolic risk factors in obese children and adolescents.
AB  - AIM: To verify the relationship between leptin and cardiometabolic risk factors
      in obese children and adolescents. METHODS: A cross-sectional study evaluated 200
      children and adolescents treated in Campina Grande, Brazil, from April 2009 to
      March 2010. Leptin, fasting glucose, insulin, homeostasis model assessment of
      insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and
      triglycerides were determined. The t-test was used to compare leptin means of two
      groups and analysis of variance to compare means of three groups. Multiple
      comparisons of pairs of group means were performed with Tukey's test. In all
      tests, a significance level of 0.05 was adopted. RESULTS: The leptin sample mean
      was 22.7 +/- 10.0 MUg/L (95% confidence interval: 21.3 MUg/L to 24.1 MUg/L).
      Leptin was significantly higher in the following groups: female, teenager,
      increased waist circumference, high systolic blood pressure, elevated
      triglycerides hyperinsulinemia, insulin resistance and metabolic syndrome. Most
      cardiometabolic risk factors had higher means in the last quartile of leptin,
      except total-cholesterol, LDL-C and triglycerides levels. HDL-C was reduced in
      the last quartile of leptin. Simple linear regression analysis showed a
      significant negative correlation between leptin and HDL-C and a positive
      correlation between leptin and triglycerides, insulin, HOMA-IR, body mass index,
      waist circumference, and systolic and diastolic blood pressure. Multiple linear
      regression models showed an independent association between leptin and HDL-C,
      triglycerides, insulin, HOMA-IR, body mass index, waist circumference, systolic
      and diastolic blood pressure, after age and gender control. CONCLUSION: Leptin
      may be a useful marker of metabolic syndrome and insulin resistance in obese
      adolescents.

PMID- 24923192
TI  - The BEL1-type homeobox gene SH5 induces seed shattering by enhancing abscission
      zone development and inhibiting lignin biosynthesis.
AB  - Seed shattering is an important trait that influences grain yield. A major
      controlling quantitative trait locus in rice is qSH1. Although the degree of
      shattering is correlated with the level of expression of qSH1, some qSH1
      defective cultivars display moderate shattering while others show a non
      shattering phenotype. Os05 g38120 (SH5) on chromosome 5 is highly homologous to
      qSH1. Although we detected SH5 transcripts in various organs, this gene was
      highly expressed at the abscission zone (AZ) in the pedicels. When expression of
      this gene was suppressed in easy-shattering 'Kasalath', development of the AZ was
      reduced and thereby so was seed loss. By contrast, the extent of shattering, as
      well as AZ development, was greatly enhanced in moderate-shattering 'Dongjin'
      rice when SH5 was overexpressed. Likewise, overexpression of SH5 in the non
      shattering 'Ilpum' led to an increase in seed shattering because lignin levels
      were decreased in the basal region of spikelets in the absence of development of
      an AZ. We also determined that two shattering-related genes, SHAT1 and Sh4, which
      are necessary for proper formation of an AZ, were induced by SH5. Based on these
      observations, we propose that SH5 modulates seed shattering by enhancing AZ
      development and inhibiting lignin biosynthesis. 

PMID- 24923193
TI  - Validated finite element analyses of WaveOne Endodontic Instruments: a comparison
      between M-Wire and NiTi alloys.
AB  - AIM: To validate torsional analysis, based on finite elements, of WaveOne
      instruments against in vitro tests and to model the effects of different nickel
      titanium (NiTi) materials. METHODOLOGY: WaveOne reciprocating instruments (Small,
      Primary and Large, n = 8 each, M-Wire) were tested under torsion according to
      standard ISO 3630-1. Torsional profiles including torque and angle at fracture
      were determined. Test conditions were reproduced through Finite Element Analysis
      (FEA) simulations based on micro-CT scans at 10-MUm resolution; results were
      compared to experimental data using analysis of variance and two-sided one sample
      t-tests. The same simulation was performed on virtual instruments with identical
      geometry and load condition, based on M-Wire or conventional NiTi alloy. RESULTS:
      Torsional profiles from FEA simulations were in significant agreement with the in
      vitro results. Therefore, the models developed in this study were accurate and
      able to provide reliable simulation of the torsional performance. Stock NiTi
      files under torsional tests had up to 44.9%, 44.9% and 44.1% less flexibility
      than virtual M-Wire files at small deflections for Small, Primary and Large
      instruments, respectively. As deflection levels increased, the differences in
      flexibility between the two sets of simulated instruments decreased until
      fracture. Stock NiTi instruments had a torsional fracture resistance up to 10.3%,
      8.0% and 7.4% lower than the M-Wire instruments, for the Small, Primary and Large
      file, respectively. CONCLUSION: M-Wire instruments benefitted primarily through
      higher material flexibility while still at low deflection levels, compared with
      conventional NiTi alloy. At fracture, the instruments did not take complete
      advantage of the enhanced fractural resistance of the M-Wire material, which
      determines only limited improvements of the torsional performance.

PMID- 24923194
TI  - Save the global: global signal connectivity as a tool for studying clinical
      populations with functional magnetic resonance imaging.
AB  - The global signal is commonly removed from resting-state data, as it was presumed
      to reflect physiological noise. However, removal of the global signal is now
      under debate, as this signal may reflect important neuronal components, and its
      removal may introduce artifacts into the data. Here, we show that the functional
      connectivity (FC) of the global signal is of functional relevance, as it
      differentiates between schizophrenia patients and healthy controls during rest.
      We also demonstrate that other reported findings related to various clinical
      populations may actually reflect alternations in global signal FC. The evidence
      of the clinical relevance of the global signal propose its usage as a research
      tool, and extend previously reported perils of global signal removal in resting
      state data of clinical populations.

PMID- 24923196
TI  - When did it really start or stop: the impact of censored observations on the
      analysis of duration.
AB  - Behaviour is often described in terms of bout lengths. Because of censoring, some
      of these bout lengths may only be observed partially. For instance, when
      observation is finished after a fixed period the end moment of the last bout
      remains unknown. The only available information on such a bout length is that it
      exceeds a certain value. This value is the censored observed bout length.
      Censored data are quite common in ethology, but the problem is often not
      recognized. Therefore, the well established statistical methods that account for
      censoring are rarely used in ethology. We report on the consequences of using
      standard methods instead of methods adjusted to account for censoring. We
      demonstrate that the usual methods of dealing with censored observations, such as
      treating them as uncensored observations or omitting them altogether, leads more
      often to erroneous conclusions. When an unadjusted test is used for testing the
      equality of two censored samples of bout lengths, the probability of rejecting
      the null hypothesis when the samples are different is much lower than when an
      adjusted test is used. Moreover, especially when censoring patterns differ
      between samples, the probability of wrongly rejecting the null hypothesis may be
      increased. 

PMID- 24923195
TI  - CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic
      lateral sclerosis.
AB  - BACKGROUND: Hallmarks of CNS inflammation, including microglial and astrocyte
      activation, are prominent features in post-mortem tissue from amyotrophic lateral
      sclerosis (ALS) patients and in mice overexpressing mutant superoxide dismutase-1
      (SOD1G93A). Administration of non-targeted glucocorticoids does not significantly
      alter disease progression, but this may reflect poor CNS delivery. Here, we
      sought to discover whether CNS-targeted, liposomal encapsulated glucocorticoid
      would inhibit the CNS inflammatory response and reduce motor neuron loss.
      SOD1G93A mice were treated with saline, free methylprednisolone (MP, 10
      mg/kg/week) or glutathione PEGylated liposomal MP (2B3-201, 10 mg/kg/week) and
      compared to saline treated wild-type animals. Animals were treated weekly with
      intravenous injections for 9 weeks from 60 days of age. Weights and motor
      performance were monitored during this period. At the end of the experimental
      period (116 days) mice were imaged using T2-weighted MRI for brainstem pathology;
      brain and spinal cord tissue were then collected for histological analysis.
      RESULTS: All SOD1G93A groups showed a significant decrease in motor performance,
      compared to baseline, from ~100 days. SOD1G93A animals showed a significant
      increase in signal intensity on T2 weighted MR images, which may reflect the
      combination of neuronal vacuolation and glial activation in these motor nuclei.
      Treatment with 2B3-201, but not free MP, significantly reduced T2 hyperintensity
      observed in SOD1G93A mice. Compared to saline-treated and free-MP-treated
      SOD1G93A mice, those animals given 2B3-201 displayed significantly improved
      histopathological outcomes in brainstem motor nuclei, which included reduced
      gliosis and neuronal loss. CONCLUSIONS: In contrast to previous reports that
      employed free steroid preparations, CNS-targeted anti-inflammatory agent 2B3-201
      (liposomal methylprednisolone) has therapeutic potential, reducing brainstem
      pathology in the SOD1G93A mouse model of ALS. 2B3-201 reduced neuronal loss and
      vacuolation in brainstem nuclei, and reduced activation preferentially in
      astrocytes compared with microglia. These data also suggest that other previously
      ineffective therapies could be of therapeutic value if delivered specifically to
      the CNS.

PMID- 24923197
TI  - Hybrid vigour and maternal environment in mice. I. Body and brain growth.
AB  - Ovarian grafting and surrogate fostering were used to manipulate the pre- and
      postnatal maternal environments, respectively, in order that the inbred mouse
      strains BALB/c and C57BL/6J and their reciprocal F1 hybrids experienced either an
      inbred or an F1 hybrid environment pre- and/or postnatally. Results revealed
      sizeable heteroric as well as maternal environmental effects on birth, weaning
      and 100-day body weights as well as on brain weight at 100 days. The maternal
      environmental effect on brain weight was mediated by its effect on body weight,
      but there was heterosis for brain weights even when body weight was taken into
      account. At birth and weaning, inbreds appeared to benefit more from the hybrid
      maternal environment than did hybrids, but we found no evidence of increased
      variability of inbreds compared to hybrids (homeostasis) within experimental
      conditions. 

PMID- 24923198
TI  - Hybrid vigour and maternal environment in mice. II. Water escape learning, open
      field activity and spatial memory.
AB  - A combination of ovarian grafting and fostering was used to study the effects of
      pre- and postnatal maternal factors on adult behaviour. Inbred mice (BALB/c and
      C57BL/6) and F1 hybrids were compared to assess differential sensitivity to early
      maternal effects. In addition to the peculiar behavioural profile of BALB mice,
      results revealed the existence of a cognitive process in mice and confirmed the
      greater ability of F1 mice to adopt efficient escape strategies. Only postnatal
      maternal factors were shown to exert long lasting effects on behaviour, appearing
      to affect the general ability to react to a new situation rather than specific
      psychological functions. F1 hybrids proved less sensitive to such effects than
      inbred mice. 

PMID- 24923199
TI  - Hybrid vigour and maternal environment in mice. III. Hippocampal mossy fibres and
      behaviour.
AB  - Inbred BALB/c and C57BL/6 mice as well as their F1 hybrids were reared in either
      an inbred or hybrid maternal environment prenatally and/or postnatally, and were
      later tested for several behaviours prior to histological study of the brain at
      100 days after birth. Whereas measures of spatial memory showed hybrid vigour or
      overdominance, measures of hippocampal mossy fibres showed intermediate
      inheritance. Brain-behaviour correlations within a strain were generally very
      small, and effects of maternal environment on hippocampal morphology were not
      significant. 

PMID- 24923200
TI  - Food deprivation enhances both autoshaping and autoshaping impairment by a latent
      inhibition procedure.
AB  - The influence of food deprivation on acquisition of autoshaped operant behavior
      was measured. In one study separate groups of young, male rats that were deprived
      to 75%, 80%, 85%, 90%, and 95% of ad lib weight were subjected to an autoshaping
      procedure in which a 6 s delay was interposed between lever retraction (which
      occurred when rats made a lever touch, or automatically after 15 s) and food
      pellet delivery. In a second study, groups of rats were deprived to 80% or 90% of
      ad lib weight prior to testing in a latent inhibition variation of the same
      autoshaping procedure. This was done to determine if greater food deprivation
      would enhance learning which, because of the latent inhibition manipulation, is
      manifest as less lever-directed behavior. Greater food deprivation was associated
      both with fast acquisition of autoshaped lever responding and with more reliable
      failure to increase lever responding in the latent inhibition paradigm. Thus,
      increasing food deprivation was associated with enhanced acquisition regardless
      of whether the required performance was an increase or a failure to increase the
      same behavior, indicating a specific effect on learning. 

PMID- 24923201
TI  - The organization of artificial heterospecific ant colonies. The case of the
      Manica rubida/Formica selysi association: mixed colony or parallel colonies?
AB  - We studied the spatial and social organization of homospecific and heterospecific
      colonies of two ant species Manica rubida (Myrmicanae) and Formica selysi
      (Formicinae) reared without a queen in artificial nests. We used a method based
      on individual labelling and automated photographic recording of data. The two
      species, which are forced to live together in the same artificial mixed colony,
      show the same spatial organization as they do in control homospecific colonies.
      The Manica rubida were mostly clustered in one chamber while Formica selysi
      workers were spread throughout the nest. Formica selysi individual spatial
      profiles are very heterogeneous while in the other species they are very
      homogeneous. By using taxonomical techniques on behavioural data we show that the
      two species within the mixed colony are clearly distinguishable. An artificial
      association of these two species may therefore be considered to be a
      juxtaposition of two colonies functioning in parallel, rather than a "mixed
      colony". 

PMID- 24923202
TI  - [Use of area-level socioeconomic indicators in epidemiological research:
      experience in Spain and advancement opportunities].
AB  - OBJECTIVE: To determine the use of area-level socioeconomic indicators in
      epidemiological studies in Spain. METHODS: We included studies analyzing the
      association of area-level socioeconomic indicators and health indicators in Spain
      published in peer-reviewed journals. An electronic search was conducted in PubMed
      Medline, SCI-Expanded, SSCI, Embase, and the Spanish Medical Index (until
      December 31, 2012). A manual search was also conducted of the references of the
      selected studies. Each of the articles initially selected on the basis of the
      title and abstract was reviewed by two investigators. Information was obtained on
      the publication and methodology (design and study areas, information sources,
      health and socioeconomic indicators, and statistical analysis). RESULTS: We
      included 142 studies published since 1988 (58.4% since 2005). More than half
      (59.9%) were in English. The level of analysis was ecological in 73.2% and
      multilevel in 19.0%. The areas most frequently analyzed were census tracts (35
      studies), especially within cities or autonomous regions, followed by the
      provinces (30 studies), mostly concerning Spain overall. The dependent variable
      most frequently analyzed was mortality and the socioeconomic dimension most
      commonly used was employment (71.1%). CONCLUSIONS: In the last decade in Spain,
      there has been an increase in the number of studies examining the association of
      area-level socioeconomic and health indicators, as well as in the complexity of
      design and analysis.

PMID- 24923203
TI  - Reflections on the follow-up of long-term cancer survivors in Spain.

PMID- 24923204
TI  - Impact of school-based health promotion interventions aimed at different
      behavioral domains: a systematic review.
AB  - OBJECTIVE: Given that lifestyleshave similar determinants and that school-based
      interventions are usually targeted at all the risks that affect adolescents, the
      objective of this systematic review was to summarize the characteristics and
      effects of school-based interventions acting on different behavioral domains of
      adolescent health promotion. METHODS: The review process was conducted by two
      independent reviewers who searched PubMed, Scopus, PsycINFO, and ERIC databases
      for experimental or observational studies with at least two measures of results
      published from 2007 to 2011, given that the research information available
      doubles every 5 years. Methodological quality was assessed with a standardized
      tool. RESULTS: Information was extracted from 35 studies aiming to prevent risk
      behaviors and promote healthy nutrition, physical activity, and mental and
      holistic health. Activities were based on theoretical models and were classified
      into interactive lessons, peer mediation, environmental changes, parents' and
      community activities, and tailored messages by computer-assisted training or
      other resources, usually including multiple components. In some cases, we
      identified some moderate to large, short- and long-term effects on behavioral and
      intermediate variable. CONCLUSIONS: This exhaustive review found that well
      implemented interventions can promote adolescent health. These findings are
      consistent with recent reviews. Implications for practice, public health, and
      research are discussed.

PMID- 24923205
TI  - [Evaluation of a community program to reduce isolation in older people due to
      architectural barriers].
AB  - OBJECTIVE: Social isolation impairs health. An intervention to reduce isolation
      due to architectural barriers in elderly persons was carried out in Barcelona
      (Spain). This study aimed to evaluate its effects on health. METHODS: We
      conducted a quasi-experimental before-after study. Isolated older people were
      identified in three deprived urban areas from 2009 to 2011. Participants had
      twice-weekly outings with volunteers in a stair-climbing power wheelchair. User
      satisfaction was evaluated and perceived health status, quality of life, and
      mental health before and after four outings were compared with McNemar tests.
      RESULTS: There were 74 participants (median age: 83 years; IQR: 78-89). Perceived
      health improved by 21%, mental health by 24%, and psychological distress was
      reduced by 16%. Most participants (98%) were satisfied. CONCLUSION: The
      intervention improved perceived health and mental health. Elderly people with
      impaired mobility should not live in buildings with architectural barriers and,
      if this cannot be avoided, similar programs should be implemented.

PMID- 24923206
TI  - Hepatitis B virus infection in a cohort of HIV infected blood donors and AIDS
      patients in Sichuan, China.
AB  - BACKGROUND: Co-infections of HBV and HIV are frequent due to similar routes of
      transmission. In that transmission through blood is an important route for both
      HBV and HIV, evaluation of the prevalence of HBV in HIV infected blood donors may
      be important for transfusion safety. In addition, because the epidemiological
      characteristics of HBV in HIV infected patients and blood donors may differ from
      each other, understanding of it could be significant for therapy and prevention
      of HBV in HIV infected adults. However, data reported on these in Chinese people
      remains limited. METHODS: 614 HIV confirmed positive samples were collected from
      blood donors and patients and were screened for HBsAg and HBV DNA. The samples
      screened reactive for HBsAg or positive for HBV DNA were tested for the other
      serological markers of HBV including anti-HBs, HBeAg, anti-HBe and anti-HBc. For
      the samples tested positive for HBV DNA, the S region of HBV was amplified by
      nested PCR and the HBV genotypes were determined. RESULTS: HBV coinfections were
      found in 12.9% (79/614) HIV infected individuals including 42/417(10.1%) blood
      donors and 37/197 (18.8%) AIDS patients. In the HBsAg positive individuals, 80.0%
      were HBeAg negative in which 10.0% were HBV DNA negative and 38.3% with HBV DNA
      lower than 2000 IU/ml. The average HBV DNA levels were lower in donors than in
      patients. In the HBV DNA positive populations, HBV genotypes B, A and C accounted
      for 48.1%, 22.8% and 8.86% respectively. Mutations related to the failure of
      HBsAg detection were found in 2 of the 4 HBsAg-/HBV DNA + subjects. CONCLUSIONS:
      High prevalence of HBV in HIV infected individuals was found in this study.
      Hence, we recommend routine testing of HBV for patients newly diagnosed with
      HIV/AIDS in China. Some HIV-HBV co-infected patients remain undiagnosed if only
      conventional serological markers for HBV are used and it's important to detect
      HBV DNA for HIV infected patients. HBV DNA levels were relatively low in HBeAg
      negative patients, thus this serologic marker may be useful in prioritizing
      patients on their need for HBV treatment in settings in which HBV DNA is not
      available.

PMID- 24923207
TI  - The independent effects of maternal obesity and gestational diabetes on the
      pregnancy outcomes.
AB  - BACKGROUND: Obesity and gestational diabetes (GDM) in pregnancy are recognized
      risk factors for adverse outcomes, including cesarean section (CS), macrosomia
      and preeclampsia. The aim of this study was to investigate the independent effect
      of GDM and obesity on the adverse pregnancy outcomes at term. METHODS: A
      retrospective cohort of postpartum women, in King Khalid University Hospital,
      were stratified according to body mass index (obese >=30 kg/m2, non-obese <30
      kg/m2) and the results of GDM screening into the following groups, women with no
      obesity and no GDM (reference group), women with no obesity but with GDM, women
      with obesity but no GDM and women with both GDM and obesity. Adverse pregnancy
      outcomes included high birth weight, macrosomia, CS delivery and preeclampsia.
      Multiple logistic regression used to examine independent associations of GDM and
      obesity with macrosomia and CS. RESULTS: 2701 women were included, 44% of them
      were obese and 15% had GDM. 63% of the women with GDM were obese. There was
      significant increase in the percentage of macrosomia, P < 0.001, high birth
      weight, P < 0.001, CS, P < 0.001 and preeclampsia, P < 0.001 in women with GDM
      and obesity compared to the reference group. Obesity increased the estimated risk
      of CS delivery, odds ratio (OR) 2.16, confidence intervals (CI) 1.74-2.67. The
      combination of GDM and obesity increased the risk of macrosomia OR 3.45, CI 2.05
      5.81 and the risk of CS delivery OR 2.26, CI 1.65-3.11. CONCLUSION: Maternal
      obesity and GDM were independently associated with adverse pregnancy outcomes.
      The combination of both conditions further increase the risk.

PMID- 24923208
TI  - Comparative analysis of various electrostatic potentials on docking precision
      against cyclin-dependent kinase 2 protein: a multiple docking approach.
AB  - The fundamental of molecular modeling is the interaction and binding to form a
      complex, because it explains the action of most drugs to a receptor active site.
      In the present study, different semiempirical (RM1, AM1, PM3, MNDO) and ab initio
      (HF, DFT) charge models were investigated for their performance in prediction of
      docking pose against CDK2 proteins with their respective inhibitor. Further,
      multiple docking approaches and Prime/MM-GBSA calculations were applied to
      predict the binding mode with respective charge model against CDK2 inhibitors. A
      reliable docking result was obtained using RRD, which showed significance
      improvement on ligand binding poses and docking score accuracy to the IFD. The
      combined use of RRD and Prime/MM-GBSA method could give a high correlation
      between the predicted binding free energy and experimental biological activity.
      The preliminary results point out that AM1 could be a precious charge model for
      design of new drugs with enhanced success rate. As a very similar result was also
      found for a different system of the protein-ligand binding, the suggested scoring
      function based on AM1 method seems to be applicable in drug design. The results
      from this study can provide insights into highest success rate for design of
      potent and selective CDK2 inhibitors.

PMID- 24923209
TI  - Physiological oxygen concentration alters glioma cell malignancy and
      responsiveness to photodynamic therapy in vitro.
AB  - OBJECTIVES: The partial pressure of oxygen (pO2) in brain tumors ranges from 5 to
      15%. Nevertheless, the majority of in vitro experiments with glioblastoma
      multiforme (GBM) cell lines are carried out under an atmospheric pO2 of 19 to
      21%. Recently, 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX
      (PpIX), has been introduced to neurosurgery to allow for photodynamic diagnosis
      and photodynamic therapy (PDT) in high-grade gliomas. Here, we investigate
      whether low pO2 affects GBM cell physiology, PpIX accumulation, or PDT efficacy.
      METHODS: GBM cell lines (U-87 MG and U-251 MG) were cultured under atmospheric
      (pO2  =  19%) and physiological (pO2  =  9%) oxygen concentrations. PpIX
      accumulation and localization were investigated, and cell survival and cell death
      were observed following in vitro PDT. RESULTS: A physiological pO2 of 9%
      stimulated GBM cell migration, increased hypoxia-inducible factor (HIF)-1 alpha
      levels, and elevated resistance to camptothecin in U-87 MG cells compared to
      cultivation at a pO2 of 19%. This oxygen reduction did not alter 5-ALA-induced
      intracellular PpIX accumulation. However, physiological pO2 changed the
      responsiveness of U-87 MG but not of U-251 MG cells to in vitro PDT. Around 20%
      more irradiation light was required to kill U-87 MG cells at physiological pO2,
      resulting in reduced lactate dehydrogenase (LDH) release (one- to two-fold) and
      inhibition of caspase 3 activation. DISCUSSION: Reduction of oxygen concentration
      from atmospheric to a more physiological level can influence the malignant
      behavior and survival of GBM cell lines after in vitro PDT. Therefore, precise
      oxygen concentration control should be considered when designing and performing
      experiments with GBM cells.

PMID- 24923210
TI  - Antimicrobial susceptibility and extended-spectrum beta-lactamase rates in
      aerobic gram-negative bacteria causing intra-abdominal infections in Vietnam:
      report from the Study for Monitoring Antimicrobial Resistance Trends (SMART 2009
      2011).
AB  - Treatment options for multidrug-resistant pathogens remain problematic in many
      regions and individual countries, warranting ongoing surveillance and analysis.
      Limited antimicrobial susceptibility information is available for pathogens from
      Vietnam. This study determined the bacterial susceptibility of aerobic gram
      negative pathogens of intra-abdominal infections among patients in Vietnam during
      2009-2011. A total of 905 isolates were collected from 4 medical centers in this
      investigation as part of the Study for Monitoring Antimicrobial Resistance
      Trends. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL)
      rates among the appropriate species were determined by a central laboratory using
      Clinical and Laboratory Standards Institute methods. Among the species collected,
      Escherichia coli (48.1% ESBL-positive) and Klebsiella pneumoniae (39.5% ESBL
      positive) represented the majority (46.4%) of the isolates submitted for this
      study. Ertapenem MIC90 values were lowest for these 2 species at 0.12 and
      0.25MUg/mL and remained unchanged for ESBL-positive isolates. Imipenem MIC90
      values were also the same for all isolates and ESBL-positive strains at 0.25 and
      0.5MUg/mL, respectively. Ertapenem MIC90 values for additional species with
      sufficient numbers for analysis, including Enterobacter cloacae, Proteus
      mirabilis, Acinetobacter baumannii, and Pseudomonas aeruginosa, were 1, 0.06, >4,
      and >4MUg/mL, respectively. Analysis of beta-lactamases in a subset of 132
      phenotypically ESBL-positive Enterobacteriaceae demonstrated that CTX-M variants,
      particularly CTX-M-27 and CTX-M-15, were the predominant enzymes. High resistance
      rates in Vietnam hospitals dictate continuous monitoring as antimicrobial
      inactivating enzymes continue to spread throughout Asia and globally. 

PMID- 24923211
TI  - Mucocutaneous leishmaniasis: accuracy and molecular validation of noninvasive
      procedures in a L. (V.) braziliensis-endemic area.
AB  - The aim of this study was to evaluate the effectiveness of polymerase chain
      reaction (PCR) using Kinetoplastid DNA (kDNA) from nasal swabs (NSs), saliva, and
      oral filter paper imprints (OFPI) in diagnosing mucocutaneous leishmaniasis (ML)
      and cutaneous leishmaniasis (CL). Seventeen patients with ML, 19 patients with
      CL, and 33 controls were evaluated. In patients with ML, PCR from NS showed an
      86% diagnostic accuracy (95% confidence interval [CI] = 73.81-93.05), followed by
      saliva 74% (95% CI = 60.45-84.13) and OFPI 68% (95% CI = 54.19-79.24). The
      highest sensitivity was reached by using the NS 58.82% (95% CI = 36.01-78.39),
      followed by saliva 23.53% (95% CI = 9.56-47.26) and OFPI 5.88% (95% CI = 1.05
      26.98). The specificities of the tests were complete. The NS and OFPI were
      positive in 2 cases of CL. Mucous membrane samples exhibited a higher specificity
      compared to the Montenegro skin test and indirect immunofluorescence. NS
      sensitivity was higher than that of parasitological examinations. 

PMID- 24923212
TI  - The effects of good glycaemic control on left ventricular and coronary
      endothelial functions in patients with poorly controlled Type 2 diabetes
      mellitus.
AB  - OBJECTIVE: Diabetics are at risk for developing overt heart failure and
      subclinical left ventricular (LV) dysfunction. Also, impaired coronary flow
      reserve (CFR) reflecting coronary microvascular dysfunction is common in
      diabetics. However, no substantial data regarding the effects of good glycaemic
      control on subclinical LV dysfunction and CFR are available. CONTEXT: To
      investigate whether good glycaemic control had favourable effects on subclinical
      LV dysfunction and CFR. DESIGN: Prospective, open-label, follow-up study.
      PATIENTS: Diabetics (n = 202) were classified based on baseline HbA1C levels:
      patients with good (group 1) (<7.0%) and poor glycaemic control (>=7.0%).
      MEASUREMENTS: All patients underwent echocardiographic examination at baseline
      evaluation, and it was repeated at months 6 and 12. Based on HbA1C levels
      obtained at month 6, the patients with poor glycaemic control were divided into
      two groups: achieved (group 2) and not achieved good glycaemic control (group 3).
      RESULTS: The groups were comparable with respect to diastolic function parameters
      including left atrium diameter, mitral E/A, Sm , Em /Am , E/E' and Tei index, and
      these parameters did not significantly change at follow-up in the groups. At
      baseline, CFR was slightly higher in group 1 than in group 2 and group 3, but it
      did not reach statistically significant level. At follow-up, CFR remained
      unchanged in group 1 (P = 0.58) and group 3 (P = 0.86), but increased in group 2
      (P = 0.02: month 6 vs baseline and P = 0.004: month 12 vs baseline). CONCLUSIONS:
      Diabetics with poor and good glycaemic control were comparable with respect to
      echocardiographic parameters reflecting subclinical LV dysfunction, and good
      glycaemic control did not affect these parameters. However, good glycaemic
      control improved CFR.

PMID- 24923214
TI  - [How to push the limits in the transverse dimension? Facial asymmetry, palatal
      volume and tongue posture in children with unilateral posterior cross bite: a
      three-dimensional evaluation of early treatment].
AB  - Unilateral posterior crossbites have been reported to be one of the most
      prevalent malocclusions of the primary dentition in Caucasian children. Facial
      asymmetry due to lateral mandibular displacement in unilateral posterior
      crossbite, if not treated in the primary dentition period, may lead to an
      undesirable growth modification which results in facial asymmetry of skeletal
      origin. Irregular tongue function and posture have also been diagnosed as
      important etiological factors. Early orthodontic treatment seems to be profitable
      and desirable to create conditions for normal dental, functional and skeletal
      development of the orofacial region. Treatment success after correction of
      unilateral posterior crossbite in the primary dentition is highly questionable,
      as it is very difficult to objectively assess correction of facial asymmetry and
      irregular tongue function and posture in small, growing children. Although facial
      photography is an important diagnostic tool in orthodontics, its main
      disadvantage is that it represents a three dimensional subject in two dimensions.
      Tongue posture and function during clinical examination are difficult to assess
      and is therefore unreliable. Contemporary 3D diagnostics in unilateral posterior
      crossbite enables uninvasive, valid and objective assessment of facial
      morphology, palatal volume, tongue function and posture. It can, therefore,
      become in the future an important part of morphological and functional
      diagnostics in orthodontics and dentofacial orthopedics before, during and after
      orthodontic treatment. 

PMID- 24923215
TI  - [Methodology for clinical research in Orthodontics, the assets of the beOrtho
      website].
AB  - The rules applying to the "evidence-based" methodology strongly influenced the
      clinical research in orthodontics. However, the implementation of clinical
      studies requires rigour, important statistical and methodological knowledge, as
      well as a reliable environment in order to compile and store the data obtained
      from research. We developed the project "beOrtho.com" (based on orthodontic
      evidence) in order to fill up the gap between our desire to drive clinical
      research and the necessity of methodological rigour in the exploitation of its
      results. BeOrtho website was created to answer the issue of sample recruitment,
      data compilation and storage, while providing help for the methodological design
      of clinical studies. It allows the development and monitoring of clinical
      studies, as well as the creation of databases. On the other hand, we designed an
      evaluation grid for clinical studies which helps developing systematic reviews.
      In order to illustrate our point, we tested a research protocol evaluating the
      interest of the mandibular advancement in the framework of Class II treatment. 

PMID- 24923216
TI  - [Comparative effectiveness of maxillomandibular advancement surgery versus
      mandibular advancement device for patients with moderate or severe obstructive
      sleep area].
AB  - INTRODUCTION: Currently, positive airway pressure is the gold standard treatment
      of obstructive sleep apnea (OSA). Unfortunely, adherence rates are poor.
      Alternative therapies are mandibular advancement device (MAD) and
      maxillomandibular advancement (MMA). PATIENTS: This retrospective study compared
      both treatment effectiveness on patients with moderate and severe OSA from
      January 2005 to September 2012, and carried out predictive factor of
      effectiveness. We defined therapeutic success as an apnea hypopnea index (AHI)
      less than 15 per hour and at least a 50% reduction of the initial index. The
      difference in effectiveness has been studied using regression logistic adjusted
      on MAD versus MMA propensity score. RESULTS: This study included 198 patients. 37
      were treated by MMA, and 161 with MAD. MMA treatment was significantly more
      efficient than MAD treatment with an odds ratio of 3.22; CI95% 1.31Gamma7.82 (p =
      0.011). Younger age and lower initial AHI were predictive of increased success.
      There was no significant interaction between the treatment and morphologic
      patient factors. CONCLUSION: In our sample of patients, MMA surgery was
      significantly more efficient than MAD treatment for the patients with moderate or
      severe OSA. No morphologic characteristic was identified to determine which
      patients would benefit most from MAD versus MMA surgery.

PMID- 24923217
TI  - [Surgically assisted rapid maxillary expansion. An evaluation of different
      surgical techniques and their effect on maxillary dentoskeletal complex based on
      cone-beam computed tomography. Preliminary report].
AB  - AIM: To evaluate and compare the dentoskeletal effects associated with surgically
      assisted rapid maxillary expansion (SARME) performed with (+) and without (-)
      pterygomaxillary disjunction (PD), utilizing cone beam computed tomography
      (CBCT). MATERIALS AND METHODS: A retrospective study of 9 patients (1 male, 8
      females, mean age 18.9 years) undergoing SARME who were divided into two groups.
      In group (-PD) the surgical technique followed involved bilateral LeFort I type
      of osteotomy plus midline osteotomy. In group (+PD) same protocol was followed
      and pterygoid disjunction was performed additionally. Three-dimensional CBCT
      scans were obtained preoperatively and 3-6 month postretention. A Hyrax type
      acrylic bonded expander was used. MIMICS 14.0 (Materialise Europe, Belgium)
      software was used to evaluate transverse expansion at skeletal, dentoalveolar and
      dental level. Additionally dental inclinations, alveolar bending and the pattern
      of expansion sagittally were assessed. Wilcoxon's and Mann Whitney U tests were
      used for comparisons. RESULTS AND DISCUSSION: All linear transverse measurements
      at dental and dentoalveolar level were found to have a statistically significant
      increase (P < 0.05) in both treatment groups. No statistically significant
      differences were found between the two groups as well as within groups on
      skeletal level (except of the anterior expansion of maxilla between piriform rims
      bilaterally). In -PD group significant buccal tipping of the 1(st) premolar was
      observed as well as increased buccal bending of the alveolar crest. CONCLUSION:
      This study confirms that SARME is an effective treatment of maxillary transverse
      deficiency. CBCT is an adequate tool to assess dentoskeletal treatment effects.

PMID- 24923218
TI  - [Condylar hyperplasia: qualitative and quantitative study of temporomandibular
      joints remodeling before and after condylectomy].
AB  - PURPOSE: This retrospective study aimed to evaluate bone remodeling of temporo
      mandibular joints (TMJ) using computed tomography (CT) before and after
      condylectomy for condylar hyperplasia. MATERIAL AND METHOD: TMJ bone remodeling
      was studied by comparing the pre and postoperative CT scan of ten patients.
      Qualitative evaluation was performed by two-dimensional analysis. Three
      dimensional analysis superimpositions were done after digital condylar units
      isolation. Condylar volume modifications were measured and compared on both
      sides. Lastly, before and after surgery, we studied the radio-clinic
      correlations. RESULTS: After surgery, all the operated condyles developed a new
      cortical bone. We noticed also a thickening of the glenoid fossa. Surgical
      condylectomy leaded to a 43.5% volume reduction on the operated side and 2.14% on
      the controlateral side. On the controlateral side, most of abnormalities seen
      preoperatively disappeared after surgery. For two patients, the condylar
      resection took away over 80% of the initial volume. For these patients, we
      observed major radiologic modifications on the controlateral TMJ associated with
      symptoms of dysfunction. These problems did not worsen their quality of life.
      CONCLUSION: Both TMJ presented with bone remodelling after condylectomy. In
      condylar hyperplasia, condylectomy provides orthopaedic results on dysmorphia and
      removal of the pathological prechondroblastic zone. In the future, an earlier
      detection of this pathology may help the surgeon to treat in childhood. This
      would limit surgical excision and would avoid important dysmorphia.

PMID- 24923219
TI  - [Orthopedic treatment of dento-skeletal Class II by the association minivis +
      Forsus(TM): a clinical case].
AB  - The use of customized combination mechanics with two auxillaries such as mini
      screws and Forsus(TM) Springs that up to now have been used independently,
      achieved unexpected results in the correction of a non-surgical skeletal Class II
      malocclusion. The use of mini implants to control the canting of the occlusal
      plane that is frequently reported during the use of hyperpropulsors with fixed
      appliances made it possible to achieve a better mandibular outcome. 

PMID- 24923220
TI  - [Severe complication of a bonded mandibular lingual retainer].
AB  - Bonding a flexible spiral wire retainer to the lingual surfaces of all six
      anterior mandibular teeth is a commonly used type of retention. Complications are
      rare but can be serious enough to produce biologic damage. This article presents
      a serious complication of a lingual flexible spiral wire retainer. Four years
      after the orthodontic treatment, a 20-years-old man sought treatment for a broken
      flexible spiral wire retainer. The clinical examination showed about 35 degrees 
      of buccal root torque of that tooth. A cone-beam computed tomography image showed
      that the root and the apex of the tooth were almost completely out of the bone on
      its buccal side. Surprisingly, the tooth's vitality was preserved. The tooth was
      moved back, nearly to its original position; clinically, only a gingival
      recession remained. Orthodontists and dentists should be aware of possible
      complications of bonded retainers. Patients should be clearly informed how to
      detect problems at an early stage. 

PMID- 24923221
TI  - Long-term outcomes after intersphincteric resection for low-lying rectal cancer.
AB  - BACKGROUND: As an anus-preserving surgery for very low rectal cancer,
      intersphincteric resection (ISR), has advanced markedly over the last 20 years.
      We investigated long-term oncologic, functional, and quality of life (QOL)
      outcomes after ISR with or without partial external sphincter resection (PESR).
      METHODS: A series of 199 patients underwent curative ISR with or without PESR
      between 2000 and 2008, with 49 receiving preoperative chemoradiotherapy (CRT
      group) and 150 undergoing surgery first (surgery group). Overall survival (OS),
      disease-free survival (DFS), and local relapse-free survival (LFS) rates were
      calculated using Kaplan-Meier methods. Functional outcomes were assessed using
      the Wexner incontinence score. QOL was investigated using the Short-Form 36
      questionnaire (SF-36) and modified fecal incontinence quality of life (mFIQL)
      scale. RESULTS: After a median follow-up of 78 months (range 12-164 months),
      estimated 7-year OS, DFS, and LFS rates were 78, 67, and 80 %, respectively. LFS
      was better in the CRT group than in the surgery group (p = 0.045). Patients with
      PESR or positive circumferential resection margins showed significantly worse
      survival. The median Wexner incontinence score at >5 years was 8 in the surgery
      group and 10 in the CRT group (p = 0.01). QOL was improved in all physical and
      mental subscales of the SF-36 at >5 years. Although the mFIQL showed a relatively
      good score in all groups at >5 years, a significant difference existed between
      the CRT and surgery groups (p = 0.008). CONCLUSIONS: With long-term follow-up,
      oncologic, functional, and QOL results after ISR appear acceptable, although CRT
      is associated with disturbance.

PMID- 24923222
TI  - Defining the learning curve for team-based laparoscopic pancreaticoduodenectomy.
AB  - BACKGROUND: The purpose of this study was to define the learning curves for
      laparoscopic pancreaticoduodenectomy (LPD) with and without laparoscopic
      reconstruction, using paired surgical teams consisting of advanced laparoscopic
      trained surgeons and advanced oncologic-trained surgeons. METHODS: All patients
      undergoing PD without vein resection at a single institution were retrospectively
      analyzed. LPD was introduced by initially focusing on laparoscopic resection
      followed by open reconstruction (hybrid) for 18 months prior to attempting a
      totally LPD (TLPD) approach. Cases were compared with Chi square, Fisher's exact
      test, and Kruskal-Wallis analysis of variance (ANOVA). RESULTS: Between March
      2010 and June 2013, 140 PDs were completed at our institution, of which 56 (40 %)
      were attempted laparoscopically. In 31/56 procedures we planned to perform only
      the resection laparoscopically (hybrid), of which 7 (23 %) required premature
      conversion before completion of resection. Following the first 23 of these hybrid
      cases, a total of 25 TLPDs have been performed, of which there were no
      conversions to open. For all LPD, a significant reduction in operative times was
      identified following the first 10 patients (median 478.5 vs. 430.5 min; p =
      0.01), approaching open PD levels. After approximately 50 cases, operative times
      and estimated blood loss were consistently lower than those for open PD.
      CONCLUSIONS: In our experience of building an LPD program, the initial ten cases
      represent the biggest hurdle with respect to operative times. For an experienced
      teaching center using a staged and team-based approach, LPD appears to offer
      meaningful reductions in operative time and blood loss within the first 50 cases.

PMID- 24923223
TI  - Transcriptional regulation of gene expression by microRNAs as endogenous decoys
      of transcription factors.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) are known to produce post-transcriptional
      repression of gene expression. In light of the ability of decoy
      oligodeocynucleotides (ODNs) to sequestrate transcription factors (TFs) and the
      similar double-stranded structure between decoy ODNs and miRNAs, we proposed that
      miRNAs might act as endogenous decoy molecules to produce transcriptional
      regulation of gene expression. METHODS: Quantitative real-time RT-PCR analysis
      was used to measure the changes of miRNA and mRNA expression. Luciferase reporter
      gene activity assay was used to investigate the functional interaction between
      miRNAs and TFs. Electrophoresis mobility shift assay (EMSA) and modified
      chromatin immunoprecipitation assay (ChIP) were utilized to investigate the
      physical interactions between miRNAs and TFs. MTT cell viability assay and
      cellular DNA fragmentation ELISA were used to study apoptotic cell death.
      RESULTS: We presented here that miRNAs could regulate, either negatively or
      positively, gene expression at the transcriptional level through its decoy-like
      actions and this mechanism operates under physiological conditions to produce
      cellular functions. We identified the putative cis-elements for transcriptional
      factors NF-kappaB and NFAT in the mature miR-939 and miR-376a, respectively. We
      experimentally established the ability of these miRNAs to physically bind their
      respective target TFs, using EMSA and ChIP methods. We then utilized the
      luciferase reporter gene assay to characterize the specific regulation of
      luciferase gene activities by miR-939/pre-miR-939:NF-kappaB or miR-376a/pre-miR
      376a:NFAT interactions. Moreover, miR-939 and miR-376a produced transcriptional
      regulation of endogenous genes Bcl-xL and FasL/miR-26 that are the
      transcriptional targets for NF-kB and NFAT, respectively, but are not post
      transcriptional targets for these two miRNAs. Finally, interference of these
      miRNAs with NF-kappaB and NFAT demonstrated clear phenotypes at the cellular
      level as manifested by the regulation of neuroblastoma cell death by miR-939 and
      miR-376a. CONCLUSION: Our study identified a novel non-canonical mechanism of
      miRNAs and suggests that when considering the cellular function of miRNAs the
      decoy-like mechanism for transcriptional regulation (activation or repression)
      should be taken into account.

PMID- 24923224
TI  - Insights into mechanism kinematics for protein motion simulation.
AB  - BACKGROUND: The high demanding computational requirements necessary to carry out
      protein motion simulations make it difficult to obtain information related to
      protein motion. On the one hand, molecular dynamics simulation requires huge
      computational resources to achieve satisfactory motion simulations. On the other
      hand, less accurate procedures such as interpolation methods, do not generate
      realistic morphs from the kinematic point of view. Analyzing a protein's movement
      is very similar to serial robots; thus, it is possible to treat the protein chain
      as a serial mechanism composed of rotational degrees of freedom. Recently, based
      on this hypothesis, new methodologies have arisen, based on mechanism and robot
      kinematics, to simulate protein motion. Probabilistic roadmap method, which
      discretizes the protein configurational space against a scoring function, or the
      kinetostatic compliance method that minimizes the torques that appear in bonds,
      aim to simulate protein motion with a reduced computational cost. RESULTS: In
      this paper a new viewpoint for protein motion simulation, based on mechanism
      kinematics is presented. The paper describes a set of methodologies, combining
      different techniques such as structure normalization normalization processes,
      simulation algorithms and secondary structure detection procedures. The
      combination of all these procedures allows to obtain kinematic morphs of proteins
      achieving a very good computational cost-error rate, while maintaining the
      biological meaning of the obtained structures and the kinematic viability of the
      obtained motion. CONCLUSIONS: The procedure presented in this paper, implements
      different modules to perform the simulation of the conformational change suffered
      by a protein when exerting its function. The combination of a main simulation
      procedure assisted by a secondary structure process, and a side chain orientation
      strategy, allows to obtain a fast and reliable simulations of protein motion.

PMID- 24923225
TI  - Simulation modeling and climate change: issues and challenges.

PMID- 24923226
TI  - Polycyclic aromatic hydrocarbon distribution in serum of Saudi children using
      HPLC-FLD: marker elevations in children with asthma.
AB  - Diesel exhaust consists of a complex mixture of chemicals which contain known
      genotoxicants, one of which is polycyclic aromatic hydrocarbons (PAHs) which may
      be associated with adverse respiratory health outcomes. This study aimed to
      evaluate the distribution patterns of PAHs (anthracene, naphthalene, fluorene,
      phenanthrene, cyclopentaphenanthrene, pyrene, fluoranthene, benzanthracene,
      chrysene, benzo(e)pyrene, benzoacephenanthrylene, and benzo(a)pyrene) in serum
      collected from asthmatic and healthy control children. PAH serum levels were
      measured in samples collected from children who lived in 11 different locations
      in/round Riyadh, Saudi Arabia (Al-yarmouk, Usaibi, Sultana Al-kadema, Omrrojam,
      Kof, Janoob Dawdmi, Guberah, Arabbuah, Al-mozahemyah, Iskan Al-mazzer, and Al
      gharabi) during the period 2010-2011. Our results showed that the highest total
      mean concentrations of PAH were found in serum samples collected from people who
      lived in Sultana Aljadhida, Almozahemyah, Guberah, and Omrrojam and were 663.9,
      486.17, 412.18, and 258.6 ng ml(-1), respectively. The most prevalent PAHs in
      serum samples were naphthalene, bezanthracene, benzoacephenanthrylene,
      phenanthrene, chrysene, and benzo(a)pyrene with a frequency that ranged from 54.5
      to 90.9 % positive samples. A close monitoring of PAH pollution is strongly
      recommended, especially in food and plant samples, because of their high
      bioaccumulation capacity.

PMID- 24923229
TI  - Risk of subsequent cancers in renal cell carcinoma survivors with a family
      history.
AB  - BACKGROUND: This study aimed at elucidating the effect of family history on the
      development of subsequent cancers in renal cell carcinoma (RCC) survivors and
      aimed at assessing whether the interactions between risks of subsequent cancers
      in RCC survivors and familial risk of subsequent cancer are additive or
      multiplicative interactions. METHODS: A population-based cohort (Swedish Family
      Cancer Database) of 14,267 RCC patients diagnosed in 1990-2010 was followed for
      cancer incidence. Standardised incidence ratios (SIRs) were calculated for
      subsequent cancers in RCC survivors and in RCC survivors with a family history of
      subsequent cancer. Familial risk of subsequent cancer was calculated for
      individuals with family history of specific cancer, compared to those without.
      RESULTS: For subsequent hemangioblastoma (HB) in RCC survivors, drastically
      elevated risk was observed for the effect of family history of HB [SIR=777 (95%
      confidence interval (CI): 160-2270)] and of family history of RCC [378 (46
      1367)]. Colorectal, lung, prostate and RCCs favoured additive interactions
      between risk of subsequent cancers in RCC survivors and familial risk, while
      endocrine glands, nervous system and urinary bladder cancers favoured
      multiplicative interactions. CONCLUSIONS: Risks of subsequent HB in RCC survivors
      were tremendously modified by family history of RCC or HB, which may resemble
      characteristics of von Hippel-Lindau syndrome and show the power of present
      approach to detect heritable cancer clusters. Additive or multiplicative
      interactions found for colorectal, lung, prostate, endocrine glands, nervous
      system, urinary bladder and RCCs might raise awareness among clinicians and RCC
      survivors with a family history of seven cancers about elevated risks of
      subsequent those cancers.

PMID- 24923230
TI  - Pharmacological characterization of M-II, the major human metabolite of
      ramelteon.
AB  - The duration of action of melatonin may be important for improvements in sleep
      efficiency in insomniacs. Ramelteon, a selective melatonin agonist, is primarily
      metabolized to the active metabolite M-II, which has a longer half-life and
      greater systemic exposure than ramelteon. Hence, M-II may contribute
      significantly to the hypnotic benefits of ramelteon. We assessed the ramelteon
      like activity of M-II in vitro and in vivo using cats. Binding and functional
      studies in Chinese hamster ovary cells expressing human melatonin receptors (MT1
      or MT2) revealed that M-II binds melatonin receptors with lower affinity (Ki: 114
      and 566 pmol/l for MT1 and MT2, respectively) and has lower potency (IC50: 208
      and 1,470 pmol/l for MT1 and MT2, respectively) compared with ramelteon. However,
      higher M-II doses significantly improved sleep in cats. Thus, M-II may contribute
      to the clinical efficacy of ramelteon.

PMID- 24923231
TI  - Speech-language therapists' process of including significant others in aphasia
      rehabilitation.
AB  - BACKGROUND: Although aphasia rehabilitation should include significant others, it
      is currently unknown how this recommendation is adopted in speech-language
      therapy practice. Speech-language therapists' (SLTs) experience of including
      significant others in aphasia rehabilitation is also understudied, yet a better
      understanding of clinical reality would be necessary to facilitate implementation
      of best evidence pertaining to family interventions. AIMS: To explore the process
      through which SLTs work with significant others of people with aphasia in
      rehabilitation settings. METHODS & PROCEDURES: Individual semi-structured
      interviews were conducted with eight SLTs who had been working with persons with
      aphasia in rehabilitation centres for at least 1 year. Grounded theory principles
      were applied in analysing interview transcripts. OUTCOMES & RESULTS: A
      theoretical model was developed representing SLTs' process of working with
      significant others of persons with aphasia in rehabilitation. Including
      significant others was perceived as challenging, yet a bonus to their fundamental
      patient-centred approach. Basic interventions with significant others when they
      were available included information sharing. If necessary, significant others
      were referred to social workers or psychologists or the participants collaborated
      with those professionals. Participants rarely and only under specific conditions
      provided significant others with language exercises or trained them to
      communicate better with the aphasic person. As a result, even if participants
      felt satisfied with their efforts to offer family and friends interventions, they
      also had unachieved ideals, such as having more frequent contacts with
      significant others. CONCLUSIONS & IMPLICATIONS: If SLTs perceived work with
      significant others as a feasible necessity, rather than as a challenging bonus,
      they could be more inclined to include family and friends within therapy with the
      aim to improve their communication with the person with aphasia. SLTs could also
      be more satisfied with their practice. In order to operate these changes in
      perceptions, we suggest that SLT curriculums include in-depth training about
      family intervention, a redefinition of the concept of patient, and exploration of
      SLTs' beliefs and emotions related to significant others.

PMID- 24923232
TI  - High-protein breakfast promotes weight loss by suppressing subsequent food intake
      and regulating appetite hormones in obese Chinese adolescents.
AB  - OBJECTIVE: A high-protein diet may decrease food intake through regulating
      satiety and appetite hormones and can be an effective strategy for weight loss.
      Few studies exist on obese Chinese adolescents. METHODS AND MATERIALS: 156 obese
      Chinese adolescents were enrolled and randomly assigned to one of two
      isoenergetic breakfasts, either with egg or steamed bread. Subsequent lunchtime
      food intake was recorded 4 h later. Appetite was assessed with a visual analog
      scale. Anorexigenic hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1)
      and orexigenic hormone ghrelin were determined with radioimmunoassay at 0, 30,
      and 180 min. Body weight was recorded. The tests were repeated 3 months later.
      Analysis was performed between two tests and then two groups. Pearson's
      correlation was used for association analysis. RESULTS: Subsequent lunchtime food
      intake and body weight were decreased while satiety was increased in subjects on
      an egg breakfast, which is associated with an increase of serum PYY and GLP-1 (p
      < 0.001, respectively). There were strong correlations between weight loss,
      appetite, subsequent food intake and changes of appetite hormones. CONCLUSION: A
      high-protein breakfast promotes weight loss in obese Chinese adolescents,
      possibly through its regulation of satiety, subsequent food intake and appetite
      hormones.

PMID- 24923233
TI  - In situ reconstruction in native and prosthetic aortic infections using
      cryopreserved arterial allografts.
AB  - OBJECTIVES: To evaluate overall survival and complications of cryopreserved
      arterial allografts in aortic graft infections and infected aortic aneurysms.
      METHODS: A retrospective review of consecutive patients was conducted with native
      or prosthetic aortic infections, who underwent local debridement and in situ
      implantation of a cryopreserved aortic allograft from September 2004 to June 2012
      at the Henri Mondor University Hospital. Patient characteristics, indications for
      allograft implantation, perioperative events, bacteriological data, and events
      related to follow-up were identified. The primary outcome was overall survival.
      Overall survival was estimated using the Kaplan-Meier method. Predictors of
      postoperative mortality were identified using uni- and multivariate analysis with
      a Cox proportional hazard regression. RESULTS: During the study period, 54
      patients (45 [83%] men, mean age 66.2 +/- 10.2 years) underwent aortic
      reconstruction using cryopreserved allografts. Indications were native aortic
      infection in 17 patients and prosthetic graft infection in 37 patients, including
      seven aortoenteric fistulae. Twelve aortic reconstructions (22%) were performed
      as emergency procedures. The median duration of follow-up was 12.1 months (range
      0.4-83.6). The 30-day mortality rate was 28%. The overall mortality rate was 39%
      at a median follow-up of 12.1 months. Early significant postoperative
      complications occurred in 52% of patients. The graft-related mortality rate was
      7%. The graft-related complication rate was 19%. During follow-up, there were two
      recurrences of aortic infection and two recurrences of allograft limb occlusion.
      Multivariate survival analysis identified age, chronic renal disease, prosthetic
      infection, emergent procedure, and coronary disease as independent predictors for
      postoperative mortality. CONCLUSION: This experience with cryopreserved aortic
      allografts in aortic reconstructions shows an unsatisfactory 30-day survival
      rate, as well as a substantial early graft-related complication rate. Longer
      follow-up is needed in order to support the preferential use of cryopreserved
      allografts based on their long-term behavior.

PMID- 24923234
TI  - Benefit of catheter-directed thrombolysis for acute iliofemoral DVT: myth or
      reality?

PMID- 24923235
TI  - Magnetic resonance imaging-derived arterial peak flow in peripheral arterial
      disease: towards a standardized measurement.
AB  - OBJECTIVE: To determine the best location to measure the arterial peak flow (APF)
      in patients with peripheral arterial disease in order to facilitate clinical
      standardization. METHODS: Two hundred and fifty-nine patients with varying
      degrees of peripheral artery disease (PAD) and 48 patients without PAD were
      included. All patients underwent magnetic resonance phase-contrast imaging of the
      common femoral artery (CFA), superficial femoral artery (SFA), and popliteal
      artery (PA). APF values of patients with PAD were compared with patients with no
      PAD. The discriminative ability to identify PAD was evaluated by means of
      receiver-operator characteristic curves and the corresponding areas under the
      curve (AUC). RESULTS: Mean APF values in patients with PAD were reduced by 42%,
      55% and 59% compared with non-PAD patients for the CFA, SFA, and PA, respectively
      (p < .01). The AUC's were 0.84, 0.92, and 0.93 for the CFA, SFA, and PA,
      respectively. CONCLUSION: The APF measured at the level of the PA shows the
      largest differences between patients with PAD and patients with no PAD and the
      best discriminative ability compared with the APF acquired in the CFA or SFA. The
      PA seems to be the most suitable level for standardized flow measurements in
      patients with PAD in order to obtain relevant functional information about the
      vascular status.

PMID- 24923236
TI  - First-time events between parents and preterm infants are affected by the designs
      and routines of neonatal intensive care units.
AB  - AIM: Early parental bonding with preterm babies is particularly important, and
      the aim of our study was to explore when parents experienced what they regarded
      as important events for the first time while their infant was in the neonatal
      intensive care unit (NICU). METHODS: The study was part of a longitudinal project
      on Kangaroo Mother Care at two Swedish university hospitals. The parents of 81
      infants completed questionnaires during their infants' hospital stay. RESULTS:
      Most parents saw and touched their infants immediately after birth, but only a
      few could hold them skin to skin or swaddle them. Other important events
      identified by parents included the first time they performed care giving
      activities and did so independently, interaction and closeness with the infant,
      signs of the infant's recovery and integration into the family. The timing of the
      events depended on the physical design of the NICU, whether parents' could stay
      with their infant round-the-clock and when they were allowed to provide care
      under supervision and on their own. CONCLUSION: The design and routines of the
      NICU dictated when parents first interacted with their infants. Clinical
      guidelines that facilitate early contact with preterm babies can help parents to
      make the transition to their parental role.

PMID- 24923237
TI  - One-pot synthesis of nanocaterpillar structures via in situ nanoparticlization of
      fully conjugated poly(p-phenylene)-block-polythiophene.
AB  - 1D nanocaterpillar structures were spontaneously formed during the synthesis of
      fully conjugated poly(2,5-dihexyloxy-1,4-phenylene)-block-polythiophene due to
      the strong pi-pi interactions between the polythiophene blocks. With the
      elongation of the polythiophene block, nanostructures evolved from nanospheres to
      nanocaterpillars and their length and height increased with good control. 

PMID- 24923238
TI  - Modelling phosphorus intake, digestion, retention and excretion in growing and
      finishing pigs: model description.
AB  - Low phosphorus (P) digestibility combined with intensive pig production can
      increase P diffuse pollution and environmental load. The aim of this paper was to
      develop a deterministic, dynamic model able to represent P digestion, retention
      and ultimately excretion in growing and finishing pigs of different genotypes,
      offered access to diets of different composition. The model represented the
      limited ability of pig endogenous phytase activity to dephosphorylate phytate as
      a linear function of dietary calcium (Ca). Phytate dephosphorylation in the
      stomach by exogenous microbial phytase enzymes was expressed by a first order
      kinetics relationship. The absorption of non-phytate P from the lumen of the
      small intestine into the blood stream was set at 0.8 and the dephosphorylated
      phytate from the large intestine was assumed to be indigestible. The net
      efficiency of using digested P was set at 0.94 and assumed to be independent of
      BW, and constant across genotype and sex. P requirements for both maintenance and
      growth were made simple functions of body protein mass, and hence functions of
      animal genotype. Undigested P was assumed to be excreted in the feaces in both
      soluble and insoluble forms. If digestible P exceeded the requirements for P then
      the excess digestible P was excreted through the urinary flow; thus the model
      represented both forms of P excretion (soluble and insoluble) into the
      environment. Using a UK industry standard diet, model behaviour was investigated
      for its predictions of P digestibility, retention and excretion under different
      levels of inclusion of microbial phytase and dietary Ca, and different non
      phytate P : phytate ratios in the diet, thus covering a broad space of potential
      diet compositions. Model predictions were consistent with our understanding of P
      digestion, metabolism and excretion. Uncertainties associated with the underlying
      assumptions of the model were identified. Their consequences on model
      predictions, as well as the model evaluation are assessed in a companion paper.

PMID- 24923240
TI  - Diagnosis and management of Budd Chiari syndrome: an update.
AB  - Imaging plays a crucial role in the early detection and assessment of the extent
      of disease in Budd Chiari syndrome (BCS). Early diagnosis and intervention to
      mitigate hepatic congestion is vital to restoring hepatic function and
      alleviating portal hypertension. Interventional radiology serves a key role in
      the management of these patients. The interventionist should be knowledgeable of
      the clinical presentation as well as key imaging findings, which often dictate
      the approach to treatment. This article concisely reviews the etiology,
      pathophysiology, and clinical presentation of BCS and provides a detailed
      description of imaging and treatment options, particularly interventional
      management. 

PMID- 24923241
TI  - Recanalization and mortality rates of thrombectomy with stent-retrievers in
      octogenarian patients with acute ischemic stroke.
AB  - BACKGROUND: Our objective was to evaluate the effect of treatment with stent
      retrievers in octogenarians suffering an acute ischemic stroke. METHODS: A total
      of 150 consecutive patients with acute stroke who were treated with stent
      retrievers between April 2010 and June 2012 were retrospectively reviewed.
      Patients were divided into those <80 years old (n = 116) and those >=80 (n = 34).
      Baseline characteristics, procedure data, and endpoints (postprocedural NIHSS,
      death, and mRS at 3 months) were compared. RESULTS: High blood pressure, atrial
      fibrillation, and anticoagulation were more frequent in octogenarians (p = 0.01,
      0.003, and 0.04 respectively). There were no differences between both groups
      regarding previous intravenous thrombolysis (32.4 vs. 48.3 %, p = 0.1),
      preprocedural NIHSS (18.1 vs. 16.8, p = 0.3), procedure time (74.5 (40-114) min
      vs. 63 (38-92) min, p = 0.2), revascularization time (380.5 (298-526.3) min vs.
      350 (296.3-452.8), p = 0.3), TICI >= 2B (88.2 vs. 93.9 %, p = 0.1), and
      symptomatic haemorrhage (5.9 vs. 2.6 %, p = 0.3). Discharge NIHSS was higher in
      octogenarians (9.7 vs. 6.5, p = 0.03). Death and 3-month mRS >=3 were more
      frequent in octogenarians (35.3 vs. 17.2 %, p = 0.02 and 73.5 vs. 37.1 %, p =
      0.02). ICA-involvement and prolonged revascularization involved higher mortality
      (66.7 vs. 27.6 %, p = 0.03) and worse mRS (50 vs. 24.4 %, p = 0.06) in
      octogenarians. CONCLUSIONS: In our series, treatment with stent-retrievers in
      octogenarians with acute ischemic stroke achieved good rates of recanalization
      but with a high mortality rate. ICA involvement and revascularization times
      beyond 6 hours associated to a worse prognosis. These data might be of value in
      the design of prospective studies evaluating the clinical efficacy of the
      endovascular treatments in octogenarians.

PMID- 24923239
TI  - Neonatal melanocortin receptor agonist treatment reduces play fighting and
      promotes adult attachment in prairie voles in a sex-dependent manner.
AB  - The melanocortin receptor (MCR) system has been studied extensively for its role
      in feeding and sexual behavior, but effects on social behavior have received
      little attention. alpha-MSH interacts with neural systems involved in sociality,
      including oxytocin, dopamine, and opioid systems. Acute melanotan-II (MTII), an
      MC3/4R agonist, potentiates brain oxytocin (OT) release and facilitates OT
      dependent partner preference formation in socially monogamous prairie voles. Here
      we examined the long-term impact of early-life MCR stimulation on hypothalamic
      neuronal activity and social development in prairie voles. Male and female voles
      were given daily subcutaneous injections of 10 mg/kg MTII or saline between
      postnatal days (PND) 1-7. Neonatally-treated males displayed a reduction in
      initiated play fighting bouts as juveniles compared to control males. Neonatal
      exposure to MTII facilitated partner preference formation in adult females, but
      not males, after a brief cohabitation with an opposite-sex partner. Acute MTII
      injection elicited a significant burst of the immediate early gene EGR-1
      immunoreactivity in hypothalamic OT, vasopressin, and corticotrophin releasing
      factor neurons, when tested in PND 6-7 animals. Daily neonatal treatment with 1
      mg/kg of a more selective, brain penetrant MC4R agonist, PF44687, promoted adult
      partner preferences in both females and males compared with vehicle controls.
      Thus, developmental exposure to MCR agonists lead to a persistent change in
      social behavior, suggestive of structural or functional changes in the neural
      circuits involved in the formation of social relationships. 

PMID- 24923242
TI  - Mothers' experience of their contact with their stillborn infant: an
      interpretative phenomenological analysis.
AB  - BACKGROUND: Guidelines surrounding maternal contact with the stillborn infant
      have been contradictory over the past thirty years. Most studies have reported
      that seeing and holding the stillborn baby is associated with fewer anxiety and
      depressive symptoms among mothers of stillborn babies than not doing so. In
      contrast, others studies suggest that contact with the stillborn infant can lead
      to poorer maternal mental health outcomes. There is a lack of research focusing
      on the maternal experience of this contact. The present study aimed to
      investigate how mothers describe their experience of spending time with their
      stillborn baby and how they felt retrospectively about the decision they made to
      see and hold their baby or not. METHOD: In depth interviews were conducted with
      twenty-one mothers three months after stillbirth. All mothers had decided to see
      and the majority to hold their baby. Qualitative analysis of the interview data
      was performed using Interpretive Phenomenological Analysis. RESULTS: Six
      superordinate themes were identified: Characteristics of Contact, Physicality;
      Emotional Experience; Surreal Experience; Finality; and Decision. Having contact
      with their stillborn infant provided mothers with time to process what had
      happened, to build memories, and to 'say goodbye', often sharing the experience
      with partners and other family members. The majority of mothers felt satisfied
      with their decision to spend time with their stillborn baby. Several mothers
      talked about their fear of seeing a damaged or dead body. Some mothers
      experienced strong disbelief and dissociation during the contact. CONCLUSIONS:
      Results indicate that preparation before contact with the baby, professional
      support during the contact, and professional follow-up are crucial in order to
      prevent the development of maternal mental health problems. Fears of seeing a
      damaged or dead body should be sensitively explored and ways of coping discussed.
      Even in cases where mothers experienced intense distress during the contact with
      their stillborn baby, they still described that having had this contact was
      important and that they had taken the right decision. This indicates a need for
      giving parents an informed choice by engaging in discussions about the possible
      benefits and risks of seeing their stillborn baby.

PMID- 24923243
TI  - Mechanistic study of gold(I)-catalyzed hydroamination of alkynes: outer or inner
      sphere mechanism?
AB  - An experimental mechanistic study of the gold(I)-catalyzed hydroamination shows
      the formation of conformationally flexible auro-iminium salts Au-Im, which
      originate from the protonation of a vinyl gold species. Rotation around the C-CAu
      bond is the reason for the loss of stereospecificity of protodeauration, which
      explains the stereochemical result of the Stradiotto reaction. The ambiguity
      about inner or outer sphere mechanism is thus resolved in favor of the outer
      sphere mechanism.

PMID- 24923244
TI  - Smoking and multiple sclerosis: evidence for latitudinal and temporal variation.
AB  - There is growing evidence for the role of smoking in the aetiology of multiple
      sclerosis. We have expanded existing meta-analyses and further explored the roles
      of study design, gender, latitude and year of study with regression modelling. We
      have found a consistent association between smoking and MS with an odds ratio of
      approximately 1.5, with males at higher risk. This finding is independent of
      study design. However, latitude and year of study may have unexpected influence.
      Smoking appeared to confer a greater risk to females living closer to the equator
      than to females at higher latitudes. The effect of cigarette smoke exposure on MS
      risk may not be fixed over time, but could be increasing. These results suggest a
      threshold model of MS risk that includes a fairly constant genetic risk (for
      Caucasian populations) together with variable environmental risks which are
      dominated by vitamin D deficiency at higher latitudes and are more significant in
      women who have an intrinsically lower threshold for development of disease. 

PMID- 24923245
TI  - Cessation and resuming of alglucosidase alfa in Pompe disease: a retrospective
      analysis.
AB  - Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa
      (rhGAA) in late-onset Pompe disease is moderately effective. Little is known
      about the clinical course after treatment termination and the resumption of ERT.
      In Switzerland, rhGAA therapy for Pompe disease was temporarily withdrawn after
      the federal court judged that the treatment costs were greatly out of proportion
      compared to the benefits. Re-treatment was initiated after the therapy was
      finally licensed. We retrospectively analysed seven Pompe patients, who underwent
      cessation and resumption of ERT (median age 43 years). The delay from first
      symptoms to final diagnosis ranged from 4 to 20 years. The demographics, clinical
      characteristics, assessments with the 6-min walking test (6-MWT), the predicted
      forced vital capacity (FVC) and muscle strength were analysed. Before initiation
      of ERT, all patients suffered from proximal muscle weakness of the lower limbs;
      one was wheelchair-bound and two patients received night-time non-invasive
      ventilation. Initial treatment stabilised respiratory function in most patients
      and improved their walking performance. After treatment cessation, upright FVC
      declined in most and the 6-MWT declined in all patients. Two patients needed
      additional non-invasive ventilatory support. Twelve months after resuming ERT,
      the respiratory and walking capacity improved again in most patients. However,
      aside for one patient, none of the patients reached the same level of respiratory
      function or distance walked in 6 min, as at the time of ERT withdrawal. We
      conclude that cessation of ERT in Pompe disease causes a decline in clinical
      function and should be avoided. Resuming treatment only partially recovers
      respiratory function and walking capacity. 

PMID- 24923246
TI  - Current state of diagnostic management of acute vertigo: a survey of neurologists
      in Germany.

PMID- 24923247
TI  - Stopping power of liquid water for carbon ions in the energy range between 1 MeV
      and 6 MeV.
AB  - The stopping power of liquid water was measured for the first time for carbon
      ions in the energy range between 1 and 6 MeV using the inverted Doppler shift
      attenuation method. The feasibility study carried out within the scope of the
      present work shows that this method is well suited for the quantification of the
      controversial condensed phased effect in the stopping power for heavy ions in the
      intermediate energy range. The preliminary results of this work indicate that the
      stopping power of water for carbon ions with energies prevailing in the Bragg
      peak region is significantly lower than that of water vapor. In view of the
      relatively high uncertainty of the present results, a new experiment with
      uncertainties less than the predicted difference between the stopping powers of
      both water phases is planned. 

PMID- 24923248
TI  - From mobile phone data to the spatial structure of cities.
AB  - Pervasive infrastructures, such as cell phone networks, enable to capture large
      amounts of human behavioral data but also provide information about the structure
      of cities and their dynamical properties. In this article, we focus on these last
      aspects by studying phone data recorded during 55 days in 31 Spanish cities. We
      first define an urban dilatation index which measures how the average distance
      between individuals evolves during the day, allowing us to highlight different
      types of city structure. We then focus on hotspots, the most crowded places in
      the city. We propose a parameter free method to detect them and to test the
      robustness of our results. The number of these hotspots scales sublinearly with
      the population size, a result in agreement with previous theoretical arguments
      and measures on employment datasets. We study the lifetime of these hotspots and
      show in particular that the hierarchy of permanent ones, which constitute the
      'heart' of the city, is very stable whatever the size of the city. The spatial
      structure of these hotspots is also of interest and allows us to distinguish
      different categories of cities, from monocentric and "segregated" where the
      spatial distribution is very dependent on land use, to polycentric where the
      spatial mixing between land uses is much more important. These results point
      towards the possibility of a new, quantitative classification of cities using
      high resolution spatio-temporal data. 

PMID- 24923249
TI  - Improved MR venography using quantitative susceptibility-weighted imaging.
AB  - PURPOSE: To remove the geometry dependence of phase-based susceptibility
      weighting masks in susceptibility-weighted imaging (SWI) and to improve the
      visualization of the veins and microbleeds. MATERIALS AND METHODS: True SWI
      (tSWI) was generated using susceptibility-based masks. Simulations were used to
      evaluate the influence of the characteristic parameters defining the mask. In
      vivo data from three healthy adult human volunteers were used to compare the
      contrast-to-noise-ratios (CNRs) of the right septal vein and the left internal
      cerebral vein as measured from both tSWI and SWI data. A traumatic brain injury
      (TBI) patient dataset was used to illustrate qualitatively the proper
      visualization of microbleeds using tSWI. RESULTS: Compared with conventional SWI,
      tSWI improved the CNR of the two selected veins by a factor of greater than three
      for datasets with isotropic resolution and greater than 30% for datasets with
      anisotropic resolution. Veins with different orientations can be properly
      enhanced in tSWI. Furthermore, the blooming artifact due to the strong dipolar
      phase of microbleeds in conventional SWI was reduced in tSWI for the TBI case.
      CONCLUSION: The use of tSWI overcomes the geometric limitations of using phase
      and provides better visualization of the venous system, especially for data
      collected with isotropic resolution.

PMID- 24923250
TI  - A barcode of organellar genome polymorphisms identifies the geographic origin of
      Plasmodium falciparum strains.
AB  - Malaria is a major public health problem that is actively being addressed in a
      global eradication campaign. Increased population mobility through international
      air travel has elevated the risk of re-introducing parasites to elimination areas
      and dispersing drug-resistant parasites to new regions. A simple genetic marker
      that quickly and accurately identifies the geographic origin of infections would
      be a valuable public health tool for locating the source of imported outbreaks.
      Here we analyse the mitochondrion and apicoplast genomes of 711 Plasmodium
      falciparum isolates from 14 countries, and find evidence that they are non
      recombining and co-inherited. The high degree of linkage produces a panel of
      relatively few single-nucleotide polymorphisms (SNPs) that is geographically
      informative. We design a 23-SNP barcode that is highly predictive (~92%) and
      easily adapted to aid case management in the field and survey parasite migration
      worldwide. 

PMID- 24923252
TI  - Diagnostic efficacy of the diffusion weighted imaging in the characterization of
      different types of breast lesions.
AB  - PURPOSE: To evaluate the diagnostic efficacy of quantitative Diffusion-weighted
      imaging (DWI) in the characterization of breast lesions of mass and non-mass
      enhancement (NME) types. MATERIALS AND METHODS: After the institutional review
      board gave approval, DWI exams of 267 women with 212 suspicious masses, 73 NMEs
      were retrospectively analyzed. Apparent diffusion coefficients (ADCs) of benign
      and malignant lesions were compared. Cutoff values were obtained by receiver
      operating characteristics analysis. Diagnostic accuracies of DWI for masses and
      NMEs were compared with the use of Chi-square test. The effect of the lesions
      histologic subtypes and size on diagnostic accuracies was evaluated. RESULTS:
      ADCs were significantly lower in malignants than in benigns for both masses (0.75
      versus 1.21 * 10(-3) mm(2) /s,) and NMEs (0.79 versus 1.06 * 10(-3) mm(2) /s)(P <
      0.001). Cutoff value was 0.90 * 10(-3) mm(2) /s for both lesion types. The
      accuracy of DWI was lower in NMEs (76.7%) than masses (89.2%) (P = 0.008)
      unrelated to lesion size. There was more overlap in ADCs of the benign and
      malignant NMEs due to the lower ADCs of the benign histologies of this group.
      CONCLUSION: Despite the lower diagnostic accuracy of DWI in NMEs, it could be
      helpful in the characterization of suspicious breast lesions of both mass and NME
      types.

PMID- 24923253
TI  - Delamanid: first global approval.
AB  - Delamanid, a nitro-dihydro-imidazooxazole derivative, has been developed by
      Otsuka Pharmaceutical for the treatment of multidrug-resistant tuberculosis (MDR
      TB). Delamanid received its first global approval for the treatment of MDR-TB in
      the European Union (EU), for use in combination with optimised background
      therapy. It is also under review for marketing in Japan for MDR-TB, the first
      drug application filed in Japan for this indication. Delamanid has been granted
      orphan drug status in both the EU and Japan. This article summarizes the
      milestones in the development of delamanid leading to this first approval for MDR
      TB. 

PMID- 24923251
TI  - Anti-nociception mediated by a kappa opioid receptor agonist is blocked by a
      delta receptor agonist.
AB  - BACKGROUND AND PURPOSE: The opioid receptor family comprises four structurally
      homologous but functionally distinct sub-groups, the MU (MOP), delta (DOP), kappa
      (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but
      not specific, a broad spectrum of behaviours due to activation of different
      opioid receptors is expected. In this study, we examine whether other opioid
      receptor systems influenced KOP-mediated antinociception. EXPERIMENTAL APPROACH:
      We used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive
      effect of systemically administered opioid agonists with varying selectivity at
      KOP receptors. Pharmacological and genetic approaches were used to analyse the
      interactions of the other opioid receptors in modulating KOP-mediated
      antinociception. KEY RESULTS: Etorphine, a potent agonist at all four opioid
      receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine
      is an efficacious KOP receptor agonist and specific KOP receptor agonists remain
      analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered
      KOP-mediated antinociception might be a form of stress-induced analgesia that is
      blocked by the anxiolytic effects of DOP receptor agonists. In support of this
      hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg.kg(-1) ),
      unmasked etorphine (3 mg.kg(-1) ) antinociception in MOP KO mice. Further, in
      wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg.kg(-1) )
      was blocked by pretreatment with the DOP agonist SNC80 (5 mg.kg(-1) ) and
      diazepam (1 mg.kg(-1) ). CONCLUSIONS AND IMPLICATIONS: Systemic DOP receptor
      agonists blocked systemic KOP antinociception, and these results identify DOP
      receptor agonists as potential agents for reversing stress-driven addictive and
      depressive behaviours mediated through KOP receptor activation. LINKED ARTICLES:
      This article is part of a themed section on Opioids: New Pathways to Functional
      Selectivity. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24923254
TI  - Continuous-flow extractive desorption electrospray ionization coupled to normal
      phase separations and for direct lipid analysis from cell extracts.
AB  - Normal phase liquid chromatography is a common mode for chiral separations. Many
      chiral amines are used as drugs or are important intermediates for drug
      synthesis. Electrospray ionization mass spectrometry is well known for its high
      sensitivity. However, when using normal phase liquid chromatography, electrospray
      ionization is hampered by the poor ionization efficiency of analytes from organic
      eluents. Continuous-flow extractive desorption electrospray ionization, which
      introduces the eluents through a hypodermic needle into the electrospray plume is
      demonstrated here for its success to interface normal phase liquid chromatography
      to mass spectrometry detection. Such an approach was shown to be as or more
      sensitive than ultraviolet detection for a selected set of aromatic amine
      functionalized enantiomers. Also demonstrated is the direct infusion of cell
      extracts to monitor phospholipids from three different bacterial cells. Despite
      their presence in non-electrospray-ionization-friendly extraction solvents,
      continuous-flow extractive desorption electrospray ionization enabled the
      sensitive detection of phospholipids and the ability to tune ion forms through
      incorporation of different spray modifiers. 

PMID- 24923256
TI  - Novel nanocomposite hydrogels consisting of layered double hydroxide with
      ultrahigh tensibility and hierarchical porous structure at low inorganic content.
AB  - A novel type of polymer nanocomposite (NC) hydrogel with extraordinary mechanical
      properties at low inorganic content is prepared and investigated. The NC
      hydrogels consist of isethionate-loaded layered double hydroxide/polyacrylamide
      (LDH-Ise/PAM) - with LDH-Ise being used because of its swelling properties - and
      no conventional organic crosslinker. The NC hydrogels exhibit an unusual
      hierarchical porous structure at the micro- and nanometer scales, and their
      elongation at break can exceed 4000%. 

PMID- 24923255
TI  - Prevalence of human noroviruses in frozen marketed shellfish, red fruits and
      fresh vegetables.
AB  - Noroviruses (NoVs), currently recognised as the most common human food-borne
      pathogens, are ubiquitous in the environment and can be transmitted to humans
      through multiple foodstuffs. In this study, we evaluated the prevalence of human
      NoV genogroups I (GI) and II (GII) in 493 food samples including soft red fruits
      (n = 200), salad vegetables (n = 210) and bivalve mollusc shellfish (n = 83),
      using the Bovine Enterovirus type 1 as process extraction control for the first
      time. Viral extractions were performed by elution concentration and genome
      detection by TaqMan Real-Time RT-PCR (RT-qPCR). Experimental contamination using
      hepatitis A virus (HAV) was used to determine the limit of detection (LOD) of the
      extraction methods. Positive detections were obtained from 2 g of digestive
      tissues of oysters or mussels kept for 16 h in seawater containing 2.0-2.7 log10
      plaque-forming units (PFU)/L of HAV. For lettuces and raspberries, the LOD was,
      respectively, estimated at 2.2 and 2.9 log10 PFU per 25 g. Of the molluscs
      tested, 8.4 and 14.4% were, respectively, positive for the presence of GI NoV and
      GII NoV RNA. Prevalence in GI NoVs varied from 11.9% for the salad vegetables
      samples to 15.5% for the red soft fruits. Only 0.5% of the salad and red soft
      fruits samples were positive for GII NoVs. These results highlight the high
      occurrence of human NoVs in foodstuffs that can be eaten raw or after a moderate
      technological processing or treatment. The determination of the risk of infection
      associated with an RT-qPCR positive sample remains an important challenge for the
      future.

PMID- 24923257
TI  - Effect of pyrimethamine treatment on male rat testicular cell population
      development.
AB  - Pyrimethamine (PYR) is a drug used in the treatment of newborn with congenital
      Toxoplasmosis. Even when PYR is highly specific against parasites, it may provoke
      neutropenia in the patients apart from other affectations, conditions that
      usually justify its suspension. Moreover, medication against congenital
      toxoplasmosis coincides with the proliferation stage of Sertoli and germ cells.
      Although, there are several reports on the effect of this drug on mature testes,
      records of its effects on the testes of young individuals yet in the process of
      growth are still lacking. This work was aimed to study the effects of in vivo
      administration of PYR in the first 21 days of life of male rat pups by evaluating
      their testicular alterations and its long-term sequels on fertility. Through the
      determination of the levels of seminiferous epithelium maturity, apoptotic index
      and cell proliferation index at 7, 14, 35 and 90 days post-natal using
      immunocytochemical studies. The fertility of the treated rats was evaluated at 90
      days. PYR-treated animals were found to undergo some kind of delays in
      seminiferous epithelium maturity, decreased cell proliferation index and an
      increase in apoptosis when compared with the control (p < 0.05). Epididymal sperm
      counts were also affected (p < 0.05). The application of folic acid (FA) in
      newborns treated with PYR decreased the severity of the problem (p < 0.05). This
      study provides strong evidence that the effect of PYR on testicular development
      is specific. It reinforces the importance of FA application in neonates treated
      with PYR to prevent the effect of the later on spermatogenesis.

PMID- 24923258
TI  - Trauma exposure and the subsequent risk of coronary heart disease among mid-aged
      women.
AB  - The objective of the current study was to examine whether exposure to trauma in
      the form of a history of physical, mental, emotional or sexual abuse or violence
      predicted new onset of coronary heart disease (CHD) in women. In addition, this
      study aimed to examine the mediation effects of psychological, lifestyle and
      health related factors in the abuse-CHD relationship. Data from 6 surveys over 15
      years, from the Australian Longitudinal Study on Women's Health, a large
      prospective cohort study, were used. Participants from the 1946-1951 cohort who
      did not self-report heart disease at surveys 1 (1996) and 2 (1998) and who had
      provided information on other variables were included (n = 9,276). After
      adjusting for age, women who reported trauma exposure at baseline were 1.54 times
      more likely (95% confidence interval 1.29-1.83) to report new onset of CHD than
      those who did not report trauma exposure. The association between trauma and CHD
      was largely explained by psychological factors, suggesting a direct pathway
      between exposure to trauma and risk of CHD.

PMID- 24923259
TI  - Internet-based guided self-help intervention for chronic pain based on Acceptance
      and Commitment Therapy: a randomized controlled trial.
AB  - Acceptance-based psychological interventions can potentially minimize the burden
      of chronic pain. This randomized controlled trial evaluated an internet
      delivered, guided self-help intervention based on Acceptance and Commitment
      Therapy (ACT). A total of 238 chronic pain sufferers from the general population
      were randomly allocated to either ACT (n = 82), an internet-based control
      condition Expressive Writing (n = 79) or a waiting list condition (n = 77).
      Participants completed measures at baseline, posttreatment (3 months) and at a 3
      month follow-up. At follow-up, ACT participants had improved in pain interference
      in daily life (primary outcome) compared to participants in Expressive Writing
      (Cohen's d = .47), but not compared to waiting list participants (p value = .11).
      Those who adhered to the ACT-intervention (48%) did improve significantly
      compared to waiting list participants (d = .49). ACT-participants also showed
      superior improvement on depression, pain intensity, psychological inflexibility
      and pain catastrophizing (d: .28-.60). Significant clinical improvement was
      present. Especially, 28% of ACT-participants showed general clinically relevant
      improvement in pain interference, as well as in pain intensity and depression
      (vs. Expressive Writing and waiting list 5%). Given these findings, internet
      based ACT programs may be a promising treatment modality for chronic pain.

PMID- 24923260
TI  - Retrospective cohort study evaluating the impact of intraperitoneal morcellation
      on outcomes of localized uterine leiomyosarcoma.
AB  - BACKGROUND: Uterine leiomyosarcoma (ULMS) is identified in 0.1% to 0.2% of
      hysterectomy specimens of presumed leiomyoma. To date, there is no preoperative
      technique that reliably differentiates ULMS from uterine leiomyoma. Increasing
      use of minimally invasive approaches for the management of leiomyomas may result
      in inadvertently morcellated ULMS with resultant intraperitoneal dissemination of
      tumor. The objective of this study was to assess the impact of intraperitoneal
      morcellation on the outcomes of patients with ULMS. METHODS: In this
      retrospective cohort study, all patients with ULMS who attended the authors'
      institutions from 2007 to 2012 were reviewed. Demographics and outcomes were
      compared between those who underwent morcellation or total abdominal hysterectomy
      (TAH) as their first surgery for uterus-limited ULMS. RESULTS: In total, 58
      patients were identified, including 39 who underwent TAH and 19 who underwent
      intraperitoneal morcellation. Intraperitoneal morcellation was associated with a
      significantly increased risk of abdominal/pelvic recurrences (P = .001) and with
      significantly shorter median recurrence-free survival (10.8 months vs 39.6
      months; P = .002). A multivariate adjusted model demonstrated a > 3 times
      increased risk of recurrence associated with morcellation (hazard ratio, 3.18;
      95% confidence interval, 1.5-6.8; P = .003). CONCLUSIONS: Intraperitoneal
      morcellation of presumed leiomyoma worsens the outcomes of women with ULMS.
      Because there are no reliable preoperative techniques to distinguish ULMS from
      benign leiomyoma, all efforts to minimize intraperitoneal uterine morcellation
      should be considered. [See editorial on pages 000-000, this issue.]

PMID- 24923261
TI  - Primary biliary "cirrhosis": time to replace a misnomer.

PMID- 24923262
TI  - Is alcohol drinking associated with renal impairment in the general population of
      South Korea?
AB  - BACKGROUND/AIMS: We examined relationships between the average amount of daily
      alcohol intake, drinking patterns, and renal dysfunction among South Korean
      adultsaged >= 20 years. METHODS: The analysis used data from the Korean National
      Health and Nutrition Examination Survey (KNHANES), a cross-sectional survey of
      Korean civilians, conducted from January to December 2011. In this study, a
      sample of 5,251 participants was analysed. RESULTS: Compared with abstinence, the
      odds ratio for a decrease in estimated glomerular filtration rate (eGFR) was 0.14
      (95% CI: 0.01-0.91) among heavy drinkers, and 0.42 (95% CI: 0.17-0.98) among
      binge drinkers and the association between the amount of mean daily alcohol
      intake, binge-drinking status and a likelihood of reduced eGFR value showed
      significant trends (p = 0.041 and p = 0.038, respectively), after adjusting for
      age, smoking status, amount of physical activity, morbid hypertension, diabetes,
      dyslipidaemia, anaemia and body mass index. There was no significant association
      between alcohol consumption and the urine albumin to creatinine ratio in men, or
      between alcohol consumption and renal dysfunction in women. CONCLUSIONS: Alcohol
      consumption was inversely associated with a reduction in eGFR in Korean men.
      However, these findings should be interpreted cautiously, given the other harmful
      effects related to alcohol consumption, especially heavy and binge drinking.

PMID- 24923263
TI  - Application of in silico modelling to estimate toxicity of migrating substances
      from food packaging.
AB  - This study derived toxicity estimates for a set of 136 chemical migrants from
      food packaging materials using in silico (computational) modelling and read
      across approaches. Where available, the predicted results for mutagenicity and
      carcinogenicity were compared with published experimental data. As the packaging
      compounds are subject to safety assessment, the migrating substances were more
      likely to be negative for both the endpoints. A set of structural analogues with
      positive experimental data for carcinogenicity and/or mutagenicity was therefore
      used as a positive comparator. The results showed that a weight of evidence
      assembled from different in silico models and read-across from already-tested
      structurally similar compounds can provide a rapid and reliable means for rapid
      screening of new yet-untested intentional or unintentional chemical compounds
      that may migrate to packaged foodstuffs. 

PMID- 24923265
TI  - GC-MS and GC-MS/MS measurement of the cardiovascular risk factor homoarginine in
      biological samples.
AB  - L-Homoarginine (hArg) has recently emerged as a novel cardiovascular risk factor
      and to herald a poor prognosis in heart failure patients. Here, we report on the
      development and thorough validation of gas chromatography-mass spectrometry (GC
      MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) methods for the
      quantitative determination of hArg in biological samples, including human plasma,
      urine and sputum. For plasma and serum samples, ultrafiltrate (10 uL; cutoff, 10
      kDa) was used. For urine samples, native urine (10 uL) was used. For sputum,
      protein precipitation by acetone was performed. hArg is derivatized to its methyl
      ester tri(N-pentafluoropropionyl) derivative; de novo synthesized trideutero
      methyl ester hArg is used as the internal standard (IS). Alternatively,
      [guanidino-(15)N2]-arginine can be used as an IS. Quantitative analyses were
      performed after electron-capture negative-ion chemical ionization by selected-ion
      monitoring in GC-MS and selected-reaction monitoring in GC-MS/MS. We obtained
      very similar hArg concentrations by GC-MS and GC-MS/MS, suggesting that GC-MS
      suffices for accurate and precise quantification of hArg in biological samples.
      In plasma and serum samples of the same subjects very close hArg concentrations
      were measured. The plasma-to-serum hArg concentration ratio was determined to be
      1.12 +/- 0.21 (RSD, 19 %), suggesting that blood anticoagulation is not a major
      preanalytical concern in hArg analysis. In healthy subjects, the creatinine
      corrected urinary excretion of hArg varies considerably (0.18 +/- 0.22 umol/mmol,
      mean +/- SD, n = 19) unlike asymmetric dimethylarginine (ADMA, 2.89 +/- 0.89
      umol/mmol). In urine, hArg correlated with ADMA (r = 0.475, P = 0.040); in
      average, subjects excreted in the urine about 17.5 times more ADMA than hArg. In
      plasma of healthy humans, the concentration of hArg is of the order of 2 uM. hArg
      may be a low-abundance constituent of human plasma proteins. The GC-MS and GC
      MS/MS methods we report in this article are useful to study the physiology and
      pathology of hArg in experimental and clinical settings. 

PMID- 24923264
TI  - Dietary supplementation with essential amino acids boosts the beneficial effects
      of rosuvastatin on mouse kidney.
AB  - The effects of high-potency statins on renal function are controversial. To
      address the impact of statins on renal morpho-functional aspects, normotensive
      young mice were treated with rosuvastatin (Rvs). Moreover, because statins may
      impair mitochondrial function, mice received either dietary supplementation with
      an amino acid mixture enriched in essential amino acids (EAAm), which we
      previously demonstrated to increase mitochondrial biogenesis in muscle or an
      unsupplemented control diet for 1 month. Mitochondrial biogenesis and function,
      apoptosis, and insulin signaling pathway events were studied, primarily in
      cortical proximal tubules. By electron microscopy analysis, mitochondria were
      more abundant and more heterogeneous in size, with dense granules in the inner
      matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased
      protein kinase B and endothelial nitric oxide synthase phosphorylation, but the
      mammalian target of rapamycin signaling pathway was not affected. Rvs increased
      the expression of sirtuin 1, peroxisome proliferator-activated receptor gamma
      coactivator-1alpha, cytochrome oxidase type IV, cytochrome c, and mitochondrial
      biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell
      lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical
      proximal tubules, and expression of the endoplasmic reticulum-mitochondrial
      chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these
      changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic
      effect. EAAm boosts these processes and may contribute to the efficient control
      of cellular energetics and survival in the mouse kidney. This suggests that
      appropriate nutritional interventions may enhance the beneficial actions of Rvs,
      and could potentially prevent chronic renal side effects. 

PMID- 24923266
TI  - Skin and soft-tissue infections caused by Actinobaculum schaalii: report of two
      cases and literature review.
AB  - Skin and soft-tissue infections (SSTIs) caused by Actinobaculum spp. are very
      rare. In the present study, we report two cases and review the literature. The
      first case was an immunocompromised patient with an extensive cellulitis
      secondary to an inguinal abscess, and the second case was a patient with a
      pilonidal abscess. Clinical outcomes of both patients were good after surgical
      drainage and treatment with cloxacillin. The review of the literature showed that
      SSTIs caused by Actinobaculum spp. are usually located on the perineal and
      inguinal regions and can be severe, particularly in immunocompromised patients.
      SSTIs caused by Actinobaculum spp. can be overlooked because identification is
      often difficult and they can be considered as contaminants. 

PMID- 24923267
TI  - Antimicrobial susceptibility of clinical isolates of anaerobic bacteria in
      Ontario, 2010-2011.
AB  - The local epidemiology of antimicrobial susceptibility patterns in anaerobic
      bacteria is important in guiding the empiric treatment of infections. However,
      susceptibility data are very limited on anaerobic organisms, particularly among
      non-Bacteroides organisms. To determine susceptibility profiles of clinically
      significant anaerobic bacteria in Ontario Canada, anaerobic isolates from sterile
      sites submitted to Public Health Ontario Laboratory (PHOL) for identification and
      susceptibility testing were included in this study. Using the E-test method,
      isolates were tested for various antimicrobials including, penicillin, cefoxitin,
      clindamycin, meropenem, piperacillin-tazobactam and metronidazole. The MIC
      results were interpreted based on guidelines published by Clinical and Laboratory
      Standards Institute. Of 2527 anaerobic isolates submitted to PHOL, 1412 were
      either from sterile sites or bronchial lavage, and underwent susceptibility
      testing. Among Bacteroides fragilis, 98.2%, 24.7%, 1.6%, and 1.2% were resistant
      to penicillin, clindamycin, piperacillin-tazobactam, and metronidazole,
      respectively. Clostridium perfringens was universally susceptible to penicillin,
      piperacillin-tazobactam, and meropenem, whereas 14.2% of other Clostridium spp.
      were resistant to penicillin. Among Gram-positive anaerobes, Actinomyces spp.,
      Parvimonas micra and Propionibacterium spp. were universally susceptible to beta
      lactams. Eggerthella spp., Collinsella spp., and Eubacterium spp. showed variable
      resistance to penicillin. Among Gram-negative anaerobes, Fusobacterium spp.,
      Prevotella spp., and Veillonella spp. showed high resistance to penicillin but
      were universally susceptible to meropenem and piperacillin-tazobactam. The
      detection of metronidazole resistant B. fragilis is concerning as occurrence of
      these isolates is extremely rare. These data highlight the importance of ongoing
      surveillance to provide clinically relevant information to clinicians for empiric
      management of infections caused by anaerobic organisms. 

PMID- 24923269
TI  - A prospective study on time to recovery in 254 injured novice runners.
AB  - OBJECTIVES: Describe the diagnoses and the time to recovery of running-related
      injuries in novice runners. DESIGN: Prospective cohort study on injured runners.
      METHOD: This paper is a secondary data analysis of a 933-person cohort study
      (DANO-RUN) aimed at characterizing risk factors for injury in novice runners.
      Among those sustaining running-related injuries, the types of injuries and time
      to recovery is described in the present paper. All injured runners were diagnosed
      after a thorough clinical examination and then followed prospectively during
      their recovery. If they recovered completely from injury, time to recovery of
      each injury was registered. RESULTS: A total of 254 runners were injured. The
      proportion of runners diagnosed with medial tibial stress syndrome was 15%, 10%
      for patellofemoral pain, 9% for medial meniscal injury, 7% for Achilles
      tendinopathy and 5% for plantar fasciitis. Among the 220 runners (87%) recovering
      from their injury, the median time to recovery was 71 days (minimum  = 9 days,
      maximum  = 617 days). CONCLUSIONS: Medial tibial stress syndrome was the most
      common injury followed by patellofemoral pain, medial meniscal injury and
      Achilles tendinopathy. Half of the injured runners were unable to run 2*500
      meters without pain after 10 weeks. Almost 5% of the injured runners received
      surgical treatment.

PMID- 24923270
TI  - Social participation and the prevention of functional disability in older
      Japanese: the JAGES cohort study.
AB  - BACKGROUND: We examined the relationship between incident functional disability
      and social participation from the perspective of number of types of organizations
      participated in and type of social participation in a prospective cohort study.
      METHOD: The study was based on the Aichi Gerontological Evaluation Study (AGES)
      Cohort Study data. We followed 13,310 individuals aged 65 years or older for 4
      years. Analysis was carried out on 12,951 subjects, excluding 359 people whose
      information on age or sex was missing. Social participation was categorized into
      8 types. RESULTS: Compared to those that did not participate in any
      organizations, the hazard ratio (HR) was 0.83 (95% CI: 0.73-0.95) for
      participation in one, 0.72 (0.61-0.85) for participation in two, and 0.57 (0.46
      0.70) for participation in three or more different types of organizations. In
      multivariable adjusted models, participation in the following types of
      organization was protective for incident disability: local community
      organizations (HR = 0.85, 95% CI: 0.76-0.96), hobby organizations (HR = 0.75, 95%
      CI: 0.64-0.87), and sports organizations (HR = 0.64, 95% CI: 0.54-0.81).
      CONCLUSION: Social participation may decrease the risk of incident functional
      disability in older people in Japan. This effect may be strengthened by
      participation in a variety of different types of organizations. Participating in
      a local community, hobby, or sports group or organization may be especially
      effective for decreasing the risk of disability.

PMID- 24923271
TI  - The mechanism of valence-space metaphors: ERP evidence for affective word
      processing.
AB  - Embodied cognition contends that the representation and processing of concepts
      involve perceptual, somatosensory, motoric, and other physical re-experiencing
      information. In this view, affective concepts are also grounded in physical
      information. For instance, people often say "feeling down" or "cheer up" in daily
      life. These phrases use spatial information to understand affective concepts.
      This process is referred to as valence-space metaphor. Valence-space metaphors
      refer to the employment of spatial information (lower/higher space) to elaborate
      affective concepts (negative/positive concepts). Previous studies have
      demonstrated that processing affective words affects performance on a spatial
      detection task. However, the mechanism(s) behind this effect remain unclear. In
      the current study, we hypothesized that processing affective words might produce
      spatial information. Consequently, spatial information would affect the following
      spatial cue detection/discrimination task. In Experiment 1, participants were
      asked to remember an affective word. Then, they completed a spatial cue detection
      task while event-related potentials were recorded. The results indicated that the
      top cues induced enhanced amplitude of P200 component while participants kept
      positive words relative to negative words in mind. On the contrary, the bottom
      cues induced enhanced P200 amplitudes while participants kept negative words
      relative to positive words in mind. In Experiment 2, we conducted a behavioral
      experiment that employed a similar paradigm to Experiment 1, but used arrows
      instead of dots to test the attentional nature of the valence-space metaphor. We
      found a similar facilitation effect as found in Experiment 1. Positive words
      facilitated the discrimination of upper arrows, whereas negative words
      facilitated the discrimination of lower arrows. In summary, affective words might
      activate spatial information and cause participants to allocate their attention
      to corresponding locations. Valence-space metaphors might be grounded in
      attention allocation. 

PMID- 24923272
TI  - Detection of predictive markers for therapeutic stratification of salivary glands
      tumors.
AB  - Malignant tumors of salivary glands are rare lesions, often with poor prognosis.
      At present, surgery represents the only therapeutic choice, whereas chemotherapy
      is employed as palliative treatment in advanced disease. Over the years several
      molecular alterations associated with the pathogenesis and progression of the
      salivary glands tumors have been well-characterized. Particularly, the mutational
      status and/or aberrant expression of certain markers, such as EGFR, HER2, cKIT,
      BRAF and AR, also identified in some tumor histotypes of the salivary glands,
      currently represent molecular targets for new and efficacious drugs routinely
      employed in the treatment of other neoplasias, such as breast, lungs, GIST and
      melanoma. The expression analysis of these biomarkers associated with
      histomorphological data, could then provide the oncologist the opportunity to
      create a proper stratification of patients for customized therapies. This review
      represents an overview of the lesions of the salivary glands best characterized
      in terms of molecular aspects, focusing the attention on those markers and
      molecular alterations which can be important in the diagnosis as well as in the
      therapeutic stratification of these tumors. 

PMID- 24923273
TI  - Apoptosis and pro-inflammatory cytokine response of mast cells induced by
      influenza A viruses.
AB  - The pathogenesis of the influenza A virus has been investigated heavily, and both
      the inflammatory response and apoptosis have been found to have a definitive role
      in this process. The results of studies performed by the present and other groups
      have indicated that mast cells may play a role in the severity of the disease. To
      further investigate cellular responses to influenza A virus infection, apoptosis
      and inflammatory response were studied in mouse mastocytoma cell line P815. This
      is the first study to demonstrate that H1N1 (A/WSN/33), H5N1
      (A/Chicken/Henan/1/04), and H7N2 (A/Chicken/Hebei/2/02) influenza viruses can
      induce mast cell apoptosis. They were found to do this mainly through the
      mitochondria/cytochrome c-mediated intrinsic pathway, and the activation of
      caspase 8-mediated extrinsic pathway was here found to be weak. Two pro-apoptotic
      Bcl-2 homology domain 3 (BH3) -only molecules Bim and Puma appeared to be
      involved in the apoptotic pathways. When virus-induced apoptosis was inhibited in
      P815 cells using pan-caspase (Z-VAD-fmk) and caspase-9 (Z-LEHD-fmk) inhibitors,
      the replication of these three subtypes of viruses was suppressed and the
      secretions of pro-inflammatory cytokines and chemokines, including IL-6, IL-18,
      TNF-alpha, and MCP-1, decreased. The results of this study may further
      understanding of the role of mast cells in host defense and pathogenesis of
      influenza virus. They may also facilitate the development of novel therapeutic
      aids against influenza virus infection. 

PMID- 24923274
TI  - Principle-based concept analysis: intentionality in holistic nursing theories.
AB  - PURPOSE: This is a report of a principle-based concept analysis of intentionality
      in holistic nursing theories. METHOD: A principle-based concept analysis method
      was used to analyze seven holistic theories. The data included eight books and 31
      articles (1998-2011), which were retrieved through MEDLINE and CINAHL. FINDINGS:
      Erickson, Kriger, Parse, Watson, and Zahourek define intentionality as a
      capacity, a focused consciousness, and a pattern of human being. Rogers and
      Newman do not explicitly mention intentionality; however, they do explain pattern
      and consciousness (epistemology). Intentionality has been operationalized as a
      core concept of nurse-client relationships (pragmatic). The theories are
      consistent on intentionality as a noun and as an attribute of the person
      intentionality is different from intent and intention (linguistic). There is
      ambiguity concerning the boundaries between intentionality and consciousness
      (logic). Theoretically, intentionality is an evolutionary capacity to integrate
      human awareness and experience. Because intentionality is an individualized
      concept, we introduced it as "a matrix of continuous known changes" that emerges
      in two forms: as a capacity of human being and as a capacity of transpersonal
      caring. CONCLUSION: This study has produced a theoretical definition of
      intentionality and provides a foundation for future research to further
      investigate intentionality to better delineate its boundaries.

PMID- 24923275
TI  - Serum total bilirubin concentrations are inversely associated with total white
      blood cell counts in an adult population.
AB  - BACKGROUND: Several studies have shown that serum bilirubin has a protective
      effect against cardiovascular disease and that inflammation plays an important
      role in its pathogenesis. This cross-sectional study investigated whether there
      was an association between blood total white blood cell count, a simple indicator
      of inflammation, and serum total bilirubin concentration in a cohort of an adult
      population in Taiwan. METHODS: A total of 2458 apparently healthy adults (1246
      men and 1212 women) who attended health examination at a medical centre in
      central Taiwan were enrolled. We collected anthropometric measurements, fasting
      blood test results, lifestyle habits and medical history. RESULTS: Total white
      blood cell counts decreased progressively when the concentrations of total
      bilirubin increased as demonstrated in the total bilirubin quartiles. Both total
      bilirubin concentrations and total white blood cell counts showed significant
      correlations with the components of metabolic syndrome, including triglyceride
      and high-density lipoprotein cholesterol concentrations. Multivariate linear
      regression analysis revealed that, for both genders, total bilirubin showed an
      independent negative correlation with total white blood cell count after
      adjusting for conventional cardiovascular risk factors. CONCLUSIONS: Higher serum
      total bilirubin concentrations within the reference range were associated with
      lower blood total white blood cell counts, regardless of other classical
      cardiovascular risk factors.

PMID- 24923276
TI  - Developmental programming of obesity and insulin resistance: does mitochondrial
      dysfunction in oocytes play a role?
AB  - Insulin resistance is a key defect associated with obesity, type 2 diabetes and
      other metabolic diseases. While a number of factors have been suggested to cause
      defects in insulin action, there is a very strong association between
      inappropriate lipid deposition in insulin target tissues and the development of
      insulin resistance. In recent times, a large number of studies have reported
      changes in markers of mitochondrial metabolism in insulin-resistant individuals,
      leading to the theory that defects in mitochondrial substrate oxidation are
      responsible for the buildup of lipid intermediates and the development of insulin
      resistance. The primary support for the mitochondrial theory of insulin
      resistance comes from studies in skeletal muscle; however, there is recent
      evidence in murine models that mitochondrial dysfunction in oocytes may also play
      a role. Oocytes from obese or insulin-resistant mice have been shown to exhibit
      abnormalities in many different mitochondrial parameters, including mitochondrial
      morphology and membrane potential. Here we review the findings regarding the link
      between mitochondrial dysfunction and insulin resistance, and propose that
      abnormalities in mitochondrial metabolism in oocytes may predispose to the
      development of obesity and insulin resistance and thus contribute to the inter
      generational programming of metabolic disease. 

PMID- 24923277
TI  - Abdominal obesity is associated with heart disease in dogs.
AB  - BACKGROUND: The relationship between overall obesity and fat distribution in dogs
      and the development of heart disease is unclear. In the present study we
      evaluated the association between overall obesity and fat distribution and
      clinical heart disease by morphometric and computed tomography (CT)-based
      measurements. Body condition score (BCS), modified body mass index (MBMI, kg/m2),
      waist-to-hock-to-stifle distance ratio (WHSDR), waist-to-ilium wing distance
      ratio (WIWDR), and waist-to-truncal length ratio (WTLR) were compared between
      dogs with (n = 44) and without (n = 43) heart disease using receiver operating
      characteristic (ROC) analysis. Intra-abdominal fat (IAF) and subcutaneous fat
      (SQF) were measured in dogs with (n = 8) and without (n = 9) heart disease at the
      center of the fourth and fifth lumbar vertebrae by CT. RESULTS: BCS was similar
      between heart disease and healthy groups (3.6 +/- 0.2 vs. 3.3 +/- 0.1, P =
      0.126). The following morphometric measurements were greater in the heart disease
      group compared with healthy canines: MBMI (65.0 +/- 4.5 vs. 52.5 +/- 3.7 kg/m2,
      respectively, P = 0.035); WIWDR (4.1 +/- 0.1 vs. 3.1 +/- 0.1, P < 0.01); and WTLR
      (1.25 +/- 0.04 vs. 1.05 +/- 0.04, P < 0.01). However, there was no significant
      difference in WHSDR (3.6 +/- 0.1 vs. 3.7 +/- 0.2, P = 0.875). Interestingly, IAF
      was significantly increased in dogs with heart disease compared with healthy dogs
      (23.5 +/- 1.5% vs. 19.4 +/- 1.2%, P = 0.039) whereas SQF was similar between two
      groups (35.5 +/- 2.7% vs. 38.6 +/- 3.5%, P = 0.496). Of the five morphometric
      indices studied, WIWDR and WTLR provided acceptable discrimination for diagnosing
      heart disease in dogs, with areas under the ROC curve of 0.778 (95% confidence
      interval [CI]:0.683-0.874) and 0.727 (95% CI:0.619-0.835), respectively.
      CONCLUSIONS: Our data indicate that abdominal obesity, rather than overall
      obesity, is associated with heart disease in dogs. Measurements of both WIWDR and
      WTLR are particular useful for detection of an abdominal obesity in dogs.

PMID- 24923278
TI  - Ecto-protein kinases and phosphatases: an emerging field for translational
      medicine.
AB  - Progress in translational research has led to effective new treatments of a large
      number of diseases. Despite this progress, diseases including cancer and
      cardiovascular disorders still are at the top in death statistics and disorders
      such as osteoporosis and osteoarthritis represent an increasing disease burden in
      the aging population. Novel strategies in research are needed more than ever to
      overcome such diseases. The growing field of extracellular protein
      phosphorylation provides excellent opportunities to make major discoveries of
      disease mechanisms that can lead to novel therapies. Reversible
      phosphorylation/dephosphorylation of sites in the extracellular domains of
      matrix, cell-surface and trans-membrane proteins is emerging as a critical
      regulatory mechanism in health and disease. Moreover, a new concept is emerging
      from studies of extracellular protein phosphorylation: in cells where ATP is
      stored within secretory vesicles and released by exocytosis upon cell
      stimulation, phosphorylation of extracellular proteins can operate as a messenger
      operating uniquely in signaling pathways responsible for long-term cellular
      adaptation. Here, we highlight new concepts that arise from this research, and
      discuss translation of the findings into clinical applications such as
      development of diagnostic disease markers and next-generation drugs. 

PMID- 24923279
TI  - Treatment outcome and efficacy of an aligner technique--regarding incisor torque,
      premolar derotation and molar distalization.
AB  - BACKGROUND: The aim of this study was to investigate the efficacy of orthodontic
      treatment using the Invisalign(r) system. Particularly, we analyzed the influence
      of auxiliaries (Attachment/Power Ridge) as well as the staging (movement per
      aligner) on treatment efficacy. METHODS: We reviewed the tooth movements of 30
      consecutive patients who required orthodontic treatment with Invisalign(r). In
      all patients, one of the following tooth movements was performed: (1) Incisor
      Torque >10 degrees , (2) Premolar derotation >10 degrees  (3) Molar distalization
      >1.5 mm. The groups (1)-(3) were subdivided: in the first subgroup (a) the
      movements were supported with the use of an attachment, while in the subgroup (b)
      no auxiliaries were used (except incisor torque, in which Power Ridges were
      used). All tooth movements were performed in a split-mouth design. To analyze the
      clinical efficacy, pre-treatment and final plaster cast models were laser-scanned
      and the achieved tooth movement was determined by way of a surface/surface
      matching algorithm. The results were compared with the amount of tooth movement
      predicted by ClinCheck(r). RESULTS: The overall mean efficacy was 59% (SD = 0.2).
      The mean accuracy for upper incisor torque was 42% (SD = 0.2). Premolar
      derotation showed the lowest accuracy with approximately 40% (SD = 0.3).
      Distalization of an upper molar was the most effective movement, with efficacy
      approximately 87% (SD = 0.2). CONCLUSION: Incisor torque, premolar derotation and
      molar distalization can be performed using Invisalign(r) aligners. The staging
      (movement/aligner) and the total amount of planned movement have an significant
      impact on treatment efficacy.

PMID- 24923281
TI  - Detecting contaminated birthdates using generalized additive models.
AB  - BACKGROUND: Erroneous patient birthdates are common in health databases.
      Detection of these errors usually involves manual verification, which can be
      resource intensive and impractical. By identifying a frequent manifestation of
      birthdate errors, this paper presents a principled and statistically driven
      procedure to identify erroneous patient birthdates. RESULTS: Generalized additive
      models (GAM) enabled explicit incorporation of known demographic trends and birth
      patterns. With false positive rates controlled, the method identified birthdate
      contamination with high accuracy. In the health data set used, of the 58 actual
      incorrect birthdates manually identified by the domain expert, the GAM-based
      method identified 51, with 8 false positives (resulting in a positive predictive
      value of 86.0% (51/59) and a false negative rate of 12.0% (7/58)). These results
      outperformed linear time-series models. CONCLUSIONS: The GAM-based method is an
      effective approach to identify systemic birthdate errors, a common data quality
      issue in both clinical and administrative databases, with high accuracy.

PMID- 24923282
TI  - Modelling phosphorus intake, digestion, retention and excretion in growing and
      finishing pig: model evaluation.
AB  - A deterministic, dynamic model was developed, to enable predictions of phosphorus
      (P) digested, retained and excreted for different pig genotypes and under
      different dietary conditions. Before confidence can be placed on the predictions
      of the model, its evaluation was required. A sensitivity analysis of model
      predictions to +/-20% changes in the model parameters was undertaken using a
      basal UK industry standard diet and a pig genotype characterized by British
      Society Animal Science as being of 'intermediate growth'. Model outputs were most
      sensitive to the values of the efficiency of digestible P utilization for growth
      and the non-phytate P absorption coefficient from the small intestine into the
      bloodstream; all other model parameters influenced model outputs by <10%, with
      the majority of the parameters influencing outputs by <5%. Independent data sets
      of published experiments were used to evaluate model performance based on
      graphical comparisons and statistical analysis. The literature studies were
      selected on the basis of the following criteria: they were within the BW range of
      20 to 120 kg, pigs grew in a thermo-neutral environment; and they provided
      information on P intake, retention and excretion. In general, the model predicted
      satisfactorily the quantitative pig responses, in terms of P digested, retained
      and excreted, to variation in dietary inorganic P supply, Ca and phytase
      supplementation. The model performed well with 'conventional', European feed
      ingredients and poorly with 'less conventional' ones, such as dried distillers
      grains with solubles and canola meal. Explanations for these inconsistencies in
      the predictions are offered in the paper and they are expected to lead to further
      model development and improvement. The latter would include the characterization
      of the origin of phytate in pig diets.

PMID- 24923283
TI  - Smartphone teledermoscopy referrals: a novel process for improved triage of skin
      cancer patients.
AB  - In this open, controlled, multicentre and prospective observational study,
      smartphone teledermoscopy referrals were sent from 20 primary healthcare centres
      to 2 dermatology departments for triage of skin lesions of concern using a
      smartphone application and a compatible digital dermoscope. The outcome for 816
      patients referred via smartphone teledermoscopy was compared with 746 patients
      referred via the traditional paper-based system. When surgical treatment was
      required, the waiting time was significantly shorter using teledermoscopy for
      patients with melanoma, melanoma in situ, squamous cell carcinoma, squamous cell
      carcinoma in situ and basal cell carcinoma. Triage decisions were also more
      reliable with teledermoscopy and over 40% of the teledermoscopy patients could
      potentially have avoided face-to-face visits. Only 4 teledermoscopy referrals
      (0.4%) had to be excluded due to poor image quality. Smartphone teledermoscopy
      referrals allow for faster and more efficient management of patients with skin
      cancer as compared to traditional paper referrals. 

PMID- 24923284
TI  - The association between timing of initiation of antenatal care and stillbirths: a
      retrospective cohort study of pregnant women in Cape Town, South Africa.
AB  - BACKGROUND: There is renewed interest in stillbirth prevention for lower-middle
      income countries. Early initiation of and properly timed antenatal care (ANC) is
      thought to reduce the risk of many adverse birth outcomes. To this end we
      examined if timing of the first ANC visit influences the risk of stillbirth.
      METHODS: We conducted an analysis of a retrospective cohort of women (n = 34,671)
      with singleton births in a public perinatal service in Cape Town, South Africa.
      The main exposure was the gestational age at the first ANC visit. Bivariable
      analyses examining maternal characteristics by stillbirth status and gestational
      age at the first ANC visit, were conducted. Logistic regression, adjusting for
      maternal characteristics, was conducted to determine the risk of stillbirth.
      RESULTS: Of the 34,671 women who initiated ANC, 27,713 women (80%) were retained
      until delivery. The population stillbirth rate was 4.3 per 1000 births. The
      adjusted models indicated there was no effect of gestational age at first ANC
      visit on stillbirth outcomes when analyzed as a continuous variable (aOR 1.01;
      95% CI: 0.99-1.04) or in trimesters (2nd Trimester aOR 0.78, 95% CI: 0.39-1.59;
      3rd Trimester OR 1.03, 95% CI: 0.50-2.13, both with 1st Trimester as reference
      category). The findings were unchanged in sensitivity analyses of unobserved
      outcomes in non-retained women. CONCLUSION: The timing of a woman's first ANC
      visit may not be an important determinant of stillbirths in isolation. Further
      research is required to examine how quality of care, incorporating established,
      effective biomedical interventions, influences outcomes in this setting.

PMID- 24923286
TI  - Endovascular stent for iatrogenic penetrating injury of the thoracic aorta.

PMID- 24923285
TI  - Solitary kidney with renal artery aneurysm repaired by ex vivo reconstruction.
AB  - A 22-year-old pregnant female with pyelonephritis was found to have a 26-mm left
      renal artery aneurysm with unknown right kidney agenesis diagnosed by magnetic
      resonance imaging. Computed tomographic angiography with 3-dimensional
      reconstructions confirmed a saccular aneurysm localized at the bifurcation of the
      left posterior segmental artery. The patient ultimately underwent successful ex
      vivo left renal artery aneurysm repair with autotransplantation. Pathologic
      evaluation of the resected aneurysm confirmed the diagnosis of fibromuscular
      dysplasia. Fibromuscular dysplasia is the most common cause of renal artery
      stenosis and renovascular hypertension and can, in rare cases, be associated with
      the development of renal artery aneurysms. 

PMID- 24923287
TI  - Femoral vein repair of arterial infections: technical tips to reduce procedure
      time.
AB  - INTRODUCTION: Success with the neoaortoiliac system (NAIS) bypass has previously
      been reported. Drawbacks to this procedure include prolonged operative times and
      significant morbidity. The aim of this study was to evaluate whether a 2-team
      approach in addition to a consistent anastomosis technique reduces the operative
      time of the NAIS procedure. METHODS: A single-center retrospective review was
      performed for operations using femoral vein in arterial reconstruction from 2003
      to 2012. RESULTS: A total of 40 patients, 25 men and 15 women, were included for
      analysis. Median operative time for all operations was 300 minutes (interquartile
      range). Thirty-day mortality was 7.5% (n = 3). Assisted primary patency at 1 year
      was 100%. CONCLUSION: A 2-surgical team approach can reduce the operative time by
      up to 50%. This improves the attractiveness of this procedure, particularly when
      recalling that the treatment is definitive by virtue of its eradication of the
      source of infection.

PMID- 24923288
TI  - Repeated administration of ketamine can induce hippocampal neurodegeneration and
      long-term cognitive impairment via the ROS/HIF-1alpha pathway in developing rats.
AB  - BACKGROUND: Recent animal experiments have suggested that ketamine administration
      during development might induce widespread neurodegeneration and long-term
      cognitive deficits. The underlying mechanism is not fully understood. METHODS:
      Immature rat hippocampal neurons and newborn rats underwent repeated exposure to
      ketamine, ketamine+inhibitor of hypoxia-inducible factor (HIF)-1alpha(YC-1),
      ketamine+inhibitor of reactive oxygen species(ROS) (L-carnitine) or
      ketamine+Ca(2+) blocker(nimodipine). Apoptosis of the hippocampal neurons was
      analyzed by TUNEL and flow cytometry. Intracellular ROS were measured using 2',7'
      dichlorofluorescein diacetate. The expression of HIF- 1alpha and apoptosis
      related proteins was analyzed by western blot or qPCR. As these rats grew,
      behavioral tests were performed to evaluate cognitive function. RESULTS: The
      apoptotic rate in the ketamine group was significantly higher than that in the
      other groups, and the intracellular ROS levels in the ketamine and ketamine+YC-1
      groups were higher than those in the other groups. The expression of HIF- 1alpha,
      p53, BNIP3 and cleaved caspase-3 proteins increased, and the ratio of Bcl-2/Bax
      decreased in the ketamine group. The transcriptional levels of HIF-1alpha in the
      ketamine and ketamine+YC-1 groups were higher than those in the other groups.
      Cognitive deficits were found only in the ketamine group. CONCLUSION: We suggest
      that ketamine-induced neurodegeneration in neonatal rats, followed by long-term
      cognitive deficits, might be mediated via the ROS/HIF-1alpha pathway.

PMID- 24923289
TI  - Predictors of metabolic risk in childhood obesity.
AB  - Most of the complications of juvenile obesity are due to metabolic disturbances
      induced by an excessive accumulation of fat which leads to chronic diseases like
      type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Finding
      effective ways of identifying obese paediatric patients who are at increased risk
      of developing cardiovascular and metabolic complications has been recognised to
      be a promising strategy to improve prevention of complications of early obesity.
      Moreover, correctly identifying obese children who are already affected by
      metabolic co-morbidities should be a clinical priority. According to the state of
      the art summarised in this review, traditional metabolic variables included in
      the definitions of metabolic syndrome (MS), pre-diabetes, non-alcoholic fatty
      liver disease (NAFLD)/non-alcoholic steato-hepatitis and, in obese girls, the
      presence of polycystic ovary syndrome are the best available longitudinal
      predictors of CVD and T2DM among obese children and adolescents. In clinical
      practice, traditional metabolic variables included in the definitions of MS
      should be assessed in all obese children and adolescents; fasting metabolic
      variables have been proposed to identify obese patients likely to be affected by
      impaired glucose tolerance or T2DM, and ultrasound has proved to be a valid
      surrogate for biopsy in the diagnosis of NAFLD. Further large longitudinal and
      cross-sectional studies are needed to improve our chances of identifying obese
      youth at the highest metabolic risk.

PMID- 24923290
TI  - All-graphene-battery: bridging the gap between supercapacitors and lithium ion
      batteries.
AB  - Herein, we propose an advanced energy-storage system: all-graphene-battery. It
      operates based on fast surface-reactions in both electrodes, thus delivering a
      remarkably high power density of 6,450 W kg(-1)(total electrode) while also
      retaining a high energy density of 225 Wh kg(-1)(total electrode), which is
      comparable to that of conventional lithium ion battery. The performance and
      operating mechanism of all-graphene-battery resemble those of both
      supercapacitors and batteries, thereby blurring the conventional distinction
      between supercapacitors and batteries. This work demonstrates that the energy
      storage system made with carbonaceous materials in both the anode and cathode are
      promising alternative energy-storage devices.

PMID- 24923292
TI  - Computer-aided detection (CAD) of breast masses in mammography: combined
      detection and ensemble classification.
AB  - We propose a novel computer-aided detection (CAD) framework of breast masses in
      mammography. To increase detection sensitivity for various types of mammographic
      masses, we propose the combined use of different detection algorithms. In
      particular, we develop a region-of-interest combination mechanism that integrates
      detection information gained from unsupervised and supervised detection
      algorithms. Also, to significantly reduce the number of false-positive (FP)
      detections, the new ensemble classification algorithm is developed. Extensive
      experiments have been conducted on a benchmark mammogram database. Results show
      that our combined detection approach can considerably improve the detection
      sensitivity with a small loss of FP rate, compared to representative detection
      algorithms previously developed for mammographic CAD systems. The proposed
      ensemble classification solution also has a dramatic impact on the reduction of
      FP detections; as much as 70% (from 15 to 4.5 per image) at only cost of 4.6%
      sensitivity loss (from 90.0% to 85.4%). Moreover, our proposed CAD method
      performs as well or better (70.7% and 80.0% per 1.5 and 3.5 FPs per image
      respectively) than the results of mammography CAD algorithms previously reported
      in the literature. 

PMID- 24923291
TI  - In vitro and in vivo characterization of a new organic nitrate hybrid drug
      covalently bound to pioglitazone.
AB  - BACKGROUND/AIMS: Organic nitrates represent a group of nitrovasodilators that are
      clinically used for the treatment of ischemic heart disease. The new compound CLC
      3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a
      thiazolidinedione antidiabetic agent combining the peroxisome proliferator
      activated receptor gamma agonist activity of pioglitazone with the NO-donating
      activity of the nitrate moiety. METHODS: In vitro and in vivo characterization
      was performed by isometric tension recording, platelet function, bleeding time
      and detection of oxidative stress. RESULTS: In vitro, CLC-3000 displayed more
      potent vasodilation than pioglitazone alone or classical nitrates. In vitro, some
      effects on oxidative stress parameters were observed. Authentic AEN or the AEN
      containing linker CLC-1275 displayed antiaggregatory effects. In vivo treatment
      with CLC-3000 for 7 days did neither induce endothelial dysfunction nor nitrate
      tolerance nor oxidative stress. Acute or chronic administration of AEN increased
      the tail vein bleeding time in mice. CONCLUSION: In summary, the results of these
      studies demonstrate that CLC-3000 contains a vasodilative and antithrombotic
      activity that is not evident with pioglitazone alone, and that 7 days of exposure
      in vivo showed no typical signs of nitrate tolerance, endothelial dysfunction or
      other safety concerns in Wistar rats.

PMID- 24923294
TI  - Asymmetric dimethylarginine and progression of chronic kidney disease: a one-year
      follow-up study.
AB  - BACKGROUND/AIMS: Asymmetric dimethylarginine (ADMA) is a prognostic factor in
      patients with chronic kidney disease (CKD). However, the relationships among
      factors influencing the metabolism of ADMA and the CKD progression are not fully
      understood. METHODS: Serum ADMA, and variables related to the metabolism of ADMA
      were measured in 181 non-dialysis patients (CKD stages 3-5) and in 46 controls.
      Patients were assessed at baseline, and 6 and 12 months after the initiation of
      the study. RESULTS: Patients had increased baseline ADMA, advanced glycation end
      products (AGE), and advanced oxidation protein products (AOPP) compared with
      controls (P<0.001). In a total of 164 patients who completed a one-year study,
      the estimated GFR (eGFR) declined from 23.5 (17.7-36) mL/min/1.73m(2) to 21 (14.7
      31.5) (P=0.018), AGE rose from 1.58 (1.38-1.90) MUmol/L to 1.76 (1.52-2.21)
      (P<0.001), while ADMA, AOPP, tubular function, and proteinuria remained stable.
      In a multiple regression model (adjusted R(2) = 0.49, P<0.0001), the interaction
      of relatively higher baseline eGFR, i.e. > 25 mL/min/1.73m(2), with higher ADMA
      (P=0.02) and higher AOPP (P=0.04) predicted the severest decrease in eGFR per
      year. Other predictors of progression were higher baseline AGE (P<0.001),
      proteinuria (P=0.003), hypertension (P=0.01), and higher baseline eGFR (P=0.03).
      CONCLUSION: Elevated ADMA and markers of oxidative stress were strong predictors
      of progression in patients with eGFR between 25-40 mL/min/1.73m(2) , i.e. at the
      borderline of CKD stages 3-4.

PMID- 24923293
TI  - Structural basis for catalysis in a CDP-alcohol phosphotransferase.
AB  - The CDP-alcohol phosphotransferase (CDP-AP) family of integral membrane enzymes
      catalyses the transfer of a substituted phosphate group from a CDP-linked donor
      to an alcohol acceptor. This is an essential reaction for phospholipid
      biosynthesis across all kingdoms of life, and it is catalysed solely by CDP-APs.
      Here we report the 2.0 A resolution crystal structure of a representative CDP-AP
      from Archaeoglobus fulgidus. The enzyme (AF2299) is a homodimer, with each
      protomer consisting of six transmembrane helices and an N-terminal cytosolic
      domain. A polar cavity within the membrane accommodates the active site, lined
      with the residues from an absolutely conserved CDP-AP signature motif
      (D(1)xxD(2)G(1)xxAR...G(2)xxxD(3)xxxD(4)). Structures in the apo, CMP-bound, CDP
      bound and CDP-glycerol-bound states define functional roles for each of these
      eight conserved residues and allow us to propose a sequential, base-catalysed
      mechanism universal for CDP-APs, in which the fourth aspartate (D4) acts as the
      catalytic base.

PMID- 24923295
TI  - Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of
      mutations in spliceosome genes and poor prognosis.
AB  - In acute myeloid leukemia (AML), isolated trisomy 13 (AML+13) is a rare
      chromosomal abnormality whose prognostic relevance is poorly characterized. We
      analyzed the clinical course of 34 AML+13 patients enrolled in the German AMLCG
      1999 and SAL trials and performed exome sequencing, targeted candidate gene
      sequencing and gene expression profiling. Relapse-free (RFS) and overall survival
      (OS) of AML+13 patients were inferior compared to other ELN Intermediate-II
      patients (n=855) (median RFS, 7.8 vs 14.1 months, P = .006; median OS 9.3 vs.
      14.8 months, P = .004). Besides the known high frequency of RUNX1 mutations
      (75%), we identified mutations in spliceosome components in 88%, including SRSF2
      codon 95 mutations in 81%. Recurring mutations were detected in ASXL1 (44%) and
      BCOR (25%). Two patients carried mutations in CEBPZ, suggesting that CEBPZ is a
      novel recurrently mutated gene in AML. Gene expression analysis revealed a
      homogeneous expression profile including upregulation of FOXO1 and FLT3 and
      downregulation of SPRY2. This is the most comprehensive clinical and biological
      characterization of AML+13 to date, and reveals a striking clustering of lesions
      in a few genes, defining AML+13 as a genetically homogeneous subgroup with
      alterations in a few critical cellular pathways. Clinicaltrials.gov identifiers:
      AMLCG-1999: NCT00266136; AML96: NCT00180115; AML2003: NCT00180102; and AML60+:
      NCT00893373. 

PMID- 24923297
TI  - Social networking of human neutrophils within the immune system.
AB  - It is now widely recognized that neutrophils are highly versatile and
      sophisticated cells that display de novo synthetic capacity and may greatly
      extend their lifespan. In addition, concepts such as "neutrophil heterogeneity"
      and "neutrophil plasticity" have started to emerge, implying that, under
      pathological conditions, neutrophils may differentiate into discrete subsets
      defined by distinct phenotypic and functional profiles. A number of studies have
      shown that neutrophils act as effectors in both innate and adaptive
      immunoregulatory networks. In fact, once recruited into inflamed tissues,
      neutrophils engage into complex bidirectional interactions with macrophages,
      natural killer, dendritic and mesenchymal stem cells, B and T lymphocytes, or
      platelets. As a result of this cross-talk, mediated either by contact-dependent
      mechanisms or cell-derived soluble factors, neutrophils and target cells
      reciprocally modulate their survival and activation status. Altogether, these
      novel aspects of neutrophil biology have shed new light not only on the potential
      complex roles that neutrophils play during inflammation and immune responses, but
      also in the pathogenesis of several inflammatory disorders including infection,
      autoimmunity, and cancer. 

PMID- 24923296
TI  - Impact of iron overload and potential benefit from iron chelation in low-risk
      myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow
      disorders characterized by ineffective hematopoiesis, peripheral blood
      cytopenias, and potential for malignant transformation. Lower/intermediate-risk
      MDSs are associated with longer survival and high red blood cell (RBC)
      transfusion requirements resulting in secondary iron overload. Recent data
      suggest that markers of iron overload portend a relatively poor prognosis, and
      retrospective analysis demonstrates that iron chelation therapy is associated
      with prolonged survival in transfusion-dependent MDS patients. New data provide
      concrete evidence of iron's adverse effects on erythroid precursors in vitro and
      in vivo. Renewed interest in the iron field was heralded by the discovery of
      hepcidin, the main serum peptide hormone negative regulator of body iron.
      Evidence from beta-thalassemia suggests that regulation of hepcidin by
      erythropoiesis dominates regulation by iron. Because iron overload develops in
      some MDS patients who do not require RBC transfusions, the suppressive effect of
      ineffective erythropoiesis on hepcidin may also play a role in iron overload. We
      anticipate that additional novel tools for measuring iron overload and a
      molecular-mechanism-driven description of MDS subtypes will provide a deeper
      understanding of how iron metabolism and erythropoiesis intersect in MDSs and
      improve clinical management of this patient population.

PMID- 24923298
TI  - Evolving use of new oral anticoagulants for treatment of venous thromboembolism.
AB  - The new oral anticoagulants (NOACs), which include dabigatran, rivaroxaban,
      apixaban, and edoxaban, are poised to replace warfarin for treatment of the
      majority of patients with venous thromboembolism (VTE). With a rapid onset of
      action and the capacity to be administered in fixed doses without routine
      coagulation monitoring, NOACs streamline VTE treatment. In phase 3 trials in
      patients with acute symptomatic VTE, NOACs have been shown to be noninferior to
      conventional anticoagulant therapy for prevention of recurrence and are
      associated with less bleeding. Rivaroxaban and dabigatran are already licensed
      for VTE treatment in the United States, and apixaban and edoxaban are under
      regulatory consideration for this indication. As the number of approved drugs
      increases, clinicians will need to choose the right anticoagulant for the right
      VTE patient. To help with this decision, this review (1) compares the
      pharmacologic profiles of the NOACs, (2) outlines the unique design features of
      the phase 3 trials that evaluated the NOACs for VTE treatment, (3) reviews the
      results of these trials highlighting similarities and differences in the
      findings, (4) provides perspective about which VTE patients should receive
      conventional treatment or are candidates for NOACs, and (5) offers suggestions
      about how to choose among the NOACs. 

PMID- 24923299
TI  - HLA-haploidentical transplantation with regulatory and conventional T-cell
      adoptive immunotherapy prevents acute leukemia relapse.
AB  - Posttransplant relapse is still the major cause of treatment failure in high-risk
      acute leukemia. Attempts to manipulate alloreactive T cells to spare normal cells
      while killing leukemic cells have been unsuccessful. In HLA-haploidentical
      transplantation, we reported that donor-derived T regulatory cells (Tregs),
      coinfused with conventional T cells (Tcons), protected recipients against graft
      versus-host disease (GVHD). The present phase 2 study investigated whether Treg
      Tcon adoptive immunotherapy prevents posttransplant leukemia relapse. Forty-three
      adults with high-risk acute leukemia (acute myeloid leukemia 33; acute
      lymphoblastic leukemia 10) were conditioned with a total body irradiation-based
      regimen. Grafts included CD34(+) cells (mean 9.7 * 10(6)/kg), Tregs (mean 2.5 *
      10(6)/kg), and Tcons (mean 1.1 * 10(6)/kg). No posttransplant immunosuppression
      was given. Ninety-five percent of patients achieved full-donor type engraftment
      and 15% developed >=grade 2 acute GVHD. The probability of disease-free survival
      was 0.56 at a median follow-up of 46 months. The very low cumulative incidence of
      relapse (0.05) was significantly better than in historical controls. These
      results demonstrate the immunosuppressive potential of Tregs can be used to
      suppress GVHD without loss of the benefits of graft-versus-leukemia (GVL)
      activity. Humanized murine models provided insights into the mechanisms
      underlying separation of GVL from GVHD, suggesting the GVL effect is due to
      largely unopposed Tcon alloantigen recognition in bone marrow. 

PMID- 24923300
TI  - A cluster-randomized trial of task shifting and blood pressure control in Ghana:
      study protocol.
AB  - BACKGROUND: Countries in sub-Saharan Africa (SSA) are experiencing an epidemic of
      cardiovascular disease (CVD) propelled by rapidly increasing rates of
      hypertension. Barriers to hypertension control in SSA include poor access to care
      and high out-of-pocket costs. Although SSA bears 24% of the global disease
      burden, it has only 3% of the global health workforce. Given such limited
      resources, cost-effective strategies, such as task shifting, are needed to
      mitigate the rising CVD epidemic in SSA. Ghana, a country in SSA with an
      established community health worker program integrated within a national health
      insurance scheme provides an ideal platform to evaluate implementation of the
      World Health Organization (WHO) task-shifting strategy. This study will evaluate
      the comparative effectiveness of the implementation of the WHO Package targeted
      at CV risk assessment versus provision of health insurance coverage, on blood
      pressure (BP) reduction. METHODS: Using a cluster randomized design, 32 community
      health centers (CHCs) and district hospitals in Ghana will be randomized to
      either the intervention group (16 CHCs) or the control group (16 CHCs). A total
      of 640 patients with uncomplicated hypertension (BP 140-179/90-99 mm Hg and
      absence of target organ damage) will be enrolled in this study (20 patients per
      CHC). The intervention consists of WHO Package of CV risk assessment, patient
      education, initiation and titration of antihypertensive medications, behavioral
      counseling on lifestyle behaviors, and medication adherence every three months
      for 12 months. The primary outcome is the mean change in systolic BP from
      baseline to 12 months. The secondary outcomes are rates of BP control at 12
      months; levels of physical activity, percent change in weight, and dietary intake
      of fruits and vegetables at 12 months; and sustainability of intervention effects
      at 24 months. All outcomes will be assessed at baseline, six months and 12
      months. Trained community health nurses will deliver the intervention as part of
      Ghana's community-based health planning and services (CHPS) program. DISCUSSION:
      Findings from this study will provide policy makers and other stakeholders needed
      information to recommend scalable and cost-effective policy with respect to
      comprehensive CV risk reduction and hypertension control in resource-poor
      settings. TRIAL REGISTRATION: NCT01802372.

PMID- 24923302
TI  - Evaluation through literature data on standardized ileal digestibility and basal
      ileal endogenous loss of amino acids associated with barley in pigs.
AB  - This meta-analysis aimed to estimate the standardized ileal digestibility (SID)
      and the basal ileal endogenous amino acid losses (IAAend) in barley for growing
      pigs. In total, 38 different barley treatments published in 26 peer-reviewed
      papers were used for the meta-analysis containing information on dietary
      composition including amino acid (AA) contents of the assay diets, and (or)
      barley samples, as well as apparent ileal digestibility (AID) of AA in barley.
      The SID of AA was determined by either correcting AID of AA for their IAAend or
      by regression analysis between the apparent ileal digestible and total dietary AA
      contents. The SID values obtained by correcting the AID values for their IAAend
      amounted to 70%, 77%, 74% and 63% for Lys, Met, Thr and Trp, whereas those based
      on regression analysis method were 82%, 82%, 69% and 55%, respectively. Estimates
      of basal ileal endogenous loss of CP in ileal digesta varied considerably and
      averaged 11.84 g/kg dry matter intake (DMI), whereas IAAend for indispensable AA
      ranged from 0.05 g/kg DMI for Trp to 1.90 g/kg DMI for Leu. In most cases, these
      estimates were considerably higher than previously reported values for IAAend.
      The results of the present regression analysis indicate for most AA higher SID
      values compared with SID of most AA that were obtained by correcting AID values
      for IAAend. In view of the observed high variations in IAAend and the low CP
      content of the barley samples, estimating SID of AA based on literature data by
      means of the regression method may improve accuracy of SID coefficients for
      barley. In contrast, transformation of AID values into their corresponding SID
      values by using a constant correction factor for IAAend adds an additional source
      of error, thereby reducing the precision in estimating SID of AA.

PMID- 24923301
TI  - Capillary nano-immunoassay for Akt 1/2/3 and 4EBP1 phosphorylation in acute
      myeloid leukemia.
AB  - BACKGROUND: Overall cure rates in acute myeloid leukemia (AML) continue to range
      between 60-65% with disease relapse being a major cause of mortality. The PI3K
      Akt-mTOR kinase pathway plays a vital role in pro-survival signals within
      leukemic cells and inhibition of this pathway is being investigated to improve
      patient outcomes. Tracking activation of multiple signaling proteins
      simultaneously in patient samples can be challenging especially with limiting
      cell numbers within rare sub-populations. METHODS: The NanoPro 1000 system
      (ProteinSimple) is built on an automated, capillary-based immunoassay platform
      and enables a rapid and quantitative analysis of specific proteins and their
      phosphorylation states. We have utilized this nano-immunoassay to examine
      activation of Akt 1/2/3 and downstream mTOR target--eukaryotic initiation factor
      4E-Binding Protein 1 (4EBP1). RESULTS: Assays for Akt 1/2/3 and 4EBP1 were
      standardized using AML cell lines (MV4-11, MOLM-14, OCI-AML3 and HL-60) prior to
      testing in patient samples. Target inhibition was studied using mTOR 1/2
      inhibitor AZD-8055 and results were corroborated by Western blotting. The assay
      was able to quantify nanogram amounts of 4EBP1 and Akt 1/2/3 in AML cell lines
      and primary pediatric AML samples and results were quantifiable, consistent and
      reproducible. CONCLUSION: Our data provides a strong basis for testing this
      platform on a larger scale and our long term aim is to utilize this nano
      immunoassay prospectively in de-novo AML to be able to identify poor responders
      who might benefit from early introduction of targeted therapy.

PMID- 24923303
TI  - Oncogenic Fli-1 is a potential prognostic marker for the progression of
      epithelial ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy, but its
      etiology remains poorly understood. This study investigated the role of Fli-1 in
      ovarian carcinogenesis and disease survival. METHODS: Fli-1 protein expression
      was evaluated by immunohistochemistry in 104 primary epithelial ovarian cancer
      (EOC) patients with known follow-up data and 20 controls. Correlation between Fli
      1 expression and clinical characteristics was evaluated with the logistic
      regression. Kaplan Meier analysis was used to assess the impact of Fli-1
      expression on overall survival (OS) and disease-free survival (DFS). Cell
      proliferation and migration assay were used to explore the function of Fli-1 in
      ovarian cancer cells. RESULTS: Fli-1 was expressed in 74% cases and up-regulated
      in EOC tissues compared with normal control tissues (p< 0.05). The high
      expression of Fli-1 was significantly associated with advanced tumor stage,
      positive lymph nodal involvement, and poor OS and DFS (p< 0.05). Further analysis
      showed Fli-1 is an independent prognostic factor for OS and DFS. Down-regulation
      of Fli-1 inhibited cell proliferation but did not affect cell migration in SKOV3
      cells. CONCLUSIONS: This study revealed that Fli-1 played an essential role in
      the development and progression of ovarian cancers. Its overexpression is
      intimately related to malignant phenotypes and poor clinical outcome, suggesting
      that Fli-1 is a potential prognostic marker and therapeutic molecular target in
      ovarian cancer.

PMID- 24923304
TI  - Increasing summer rainfall in arid eastern-Central Asia over the past 8500 years.
AB  - A detailed and well-dated proxy record of summer rainfall variation in arid
      Central Asia is lacking. Here, we report a long-term, high resolution record of
      summer rainfall extracted from a peat bog in arid eastern-Central Asia (AECA).
      The record indicates a slowly but steadily increasing trend of summer rainfall in
      the AECA over the past 8500 years. On this long-term trend are superimposed
      several abrupt increases in rainfall on millennial timescales that correspond to
      rapid cooling events in the North Atlantic. During the last millennium, the
      hydrological climate pattern of the AECA underwent a major change. The rainfall
      in the past century has reached its highest level over the 8500-year history,
      highlighting the significant impact of the human-induced greenhouse effect on the
      hydrological climate in the AECA. Our results demonstrate that even in very dry
      eastern-Central Asia, the climate can become wetter under global warming. 

PMID- 24923306
TI  - Casting shadows on the prevalence of tanning dependence: an assessment of mCAGE
      criteria.
AB  - Recently more and more studies have reported high prevalence rates for a 'tanning
      dependence' among tanning bed users. The authors of these studies base their
      argumentation on a modified (m) version of the CAGE (Cut-down, Annoyed, Guilty
      and Eye-opener) Criteria, initially used for alcohol addiction. By means of
      cognitive interviews and a large population survey, we tested the validity of the
      mCAGE Criteria and the above-mentioned prevalence that was deduced on the basis
      of rather small collectives. Firstly, it seems that the mCAGE Criteria wording
      used so far is inconsistent, misleading and intrinsically invalid. Secondly, our
      population-based data show a much lower percentage (15%) of current sunbed users
      with potential dependence symptoms than the above-mentioned previously published
      studies. Thirdly, the usage parameters for most of the supposed 'addicts' do not
      indicate a substance addiction: 38% of the users with positive scores reported
      not having visited a tanning studio at all in the previous month, 39% did not use
      sunbeds regularly and 89% did not show signs of tolerance to UV radiation. The
      mCAGE Criteria do not seem suitable for assessing tanning dependence.

PMID- 24923305
TI  - FIP200 is involved in murine pseudomonas infection by regulating HMGB1
      intracellular translocation.
AB  - BACKGROUND: FIP200, a critical autophagy initiating protein, can participate in
      numerous cellular functions including cancer development; however, its functional
      role in P. aeruginosa infection of alveolar macrophages is unknown. METHODS: To
      investigate the role of FIP200 in host defense, we transfected murine alveolar
      macrophage MH-S cells with FIP200 siRNA. Having confirmed that FIP200 knockdown
      inhibited PAO1-induced autophagosme formation, we sought to characterize the
      underlying signaling pathways by immunoblotting. Further, we used fip200 KO mice
      to study the effects of fip200 deficiency on HMGB1 translocation. RESULTS: We
      showed that Pseudomonas PAO1 strain infection facilitated autophagosome
      formation, whereas knockdown of FIP200 inhibited autophagosome formation and
      HMGB1 expression in MH-S cells. Silencing FIP200 impaired the translocation of
      HMGB1 to cytosol of MH-S cells and almost abolished acetylation of HMGB1 during
      PAO1 infection. In contrast, FIP200 overexpression facilitated the cytosol
      translocation of HMGB1 from nuclei and increased acetylation of HMGB1 in PAO1
      infected MH-S cells. Importantly, expression and acetylation of HMGB1 were also
      significantly down-regulated in fip200 KO mice following PAO1 infection.
      CONCLUSIONS: Collectively, these findings elucidate that FIP200 may regulate
      expression and translocation of HMGB1 during PAO1 infection, which may indicate
      novel therapeutic targets to control pulmonary infection.

PMID- 24923307
TI  - Distinct nuclear orientation patterns for mouse chromosome 11 in normal B
      lymphocytes.
AB  - BACKGROUND: Characterizing the nuclear orientation of chromosomes in the three
      dimensional (3D) nucleus by multicolor banding (mBANDing) is a new approach
      towards understanding nuclear organization of chromosome territories. An mBANDing
      paint is composed of multiple overlapping subchromosomal probes that represent
      different regions of a single chromosome. In this study, we used it for the
      analysis of chromosome orientation in 3D interphase nuclei. We determined whether
      the nuclear orientation of the two chromosome 11 homologs was random or
      preferential, and if it was conserved between diploid mouse Pre B lymphocytes of
      BALB/c origin and primary B lymphocytes of congenic [T38HxBALB/c]N wild-type
      mice. The chromosome orientation was assessed visually and through a semi
      automated quantitative analysis of the radial and angular orientation patterns
      observed in both B cell types. RESULTS: Our data indicate that there are
      different preferential patterns of chromosome 11 orientation, which are not
      significantly different between both mouse cell types (p > 0.05). In the most
      common case for both cell types, both copies of chromosome 11 were oriented in
      parallel with the nuclear border. The second most common pattern in both types of
      B lymphocytes was with one homolog of chromosome 11 positioned with its telomeric
      end towards the nuclear center and with its centromeric end towards the
      periphery, while the other chromosome 11 was found parallel with the nuclear
      border. In addition to these two most common orientations present in
      approximately 50% of nuclei from each cell type, other orientations were observed
      at lower frequencies. CONCLUSIONS: We conclude that there are probabilistic, non
      random orientation patterns for mouse chromosome 11 in the mouse B lymphocytes we
      investigated (p < 0.0001).

PMID- 24923308
TI  - Informing a culturally appropriate approach to oral health and dental care for
      pre-school refugee children: a community participatory study.
AB  - BACKGROUND: Pre-school children in families of recently settled refugees often
      have very high rates of early childhood caries (ECC). ECC is associated with a
      high level of morbidity and is largely preventable, however effective culturally
      appropriate models of care are lacking. This study aimed to provide a deeper
      understanding of the refugee experience related to early oral health by exploring
      pre-school refugee families (i) understanding of ECC and child oral health, (ii)
      experiences of accessing dental services and (iii) barriers and enablers for
      achieving improved oral health. The knowledge gained will be critical to the
      development of effective early oral health programs in refugee children. METHODS:
      Community based participatory qualitative methodology using focus groups of
      resettled refugee families and community refugee nurse interviews. A community
      reference group was established and a bi-lingual community research associate was
      employed. Transcripts were analysed for thematic content using NVivo software.
      RESULTS: There were 44 participants: eight focus groups (nine countries of
      origin) and five interviews. Emergent themes were (i) the major influence of
      parents' previous experience, including their beliefs about deciduous (baby)
      teeth, traditional feeding practices and poverty; and a consequent lack of
      understanding of the importance of early oral health and early dental caries,
      (ii) the burden of resettlement including prioritising, parenting, learning about
      new foods and how to assimilate into the community, and (iii) refugees'
      difficulties in accessing both information and dental services, and the role of
      schools in addressing these issues. An Opportunities for Change Model was
      proposed. CONCLUSIONS: The main implication of the study is the demonstration of
      how enhanced understanding of the refugee experience can inform improvement in
      early oral prevention and treatment. The community participatory methodology of
      the study provided a basis for cross-cultural understanding and has already
      assisted in translating the findings and raising awareness in the provision of
      targeted refugee oral health services.

PMID- 24923309
TI  - Thermal developmental plasticity affects body size and water conservation of
      Drosophila nepalensis from the Western Himalayas.
AB  - In the Western Himalayas, Drosophila nepalensis is more abundant during the
      colder and drier winter than the warmer rainy season but the mechanistic bases of
      such adaptations are largely unknown. We tested effects of developmental
      plasticity on desiccation-related traits (body size, body melanization and water
      balance traits) that may be consistent with changes in seasonal abundance of this
      species. D. nepalensis grown at 15 degrees C has shown twofold higher body size,
      greater melanization (~15-fold), higher desiccation resistance (~55 h), hemolymph
      as well as carbohydrate content (twofold higher) as compared with corresponding
      values at 25 degrees C. Water loss before succumbing to death was much higher
      (~16%) at 15 degrees C than 25 degrees C. Developmental plastic effects on body
      size are associated with changes in water balance-related traits (bulk water,
      hemolymph and dehydration tolerance). The role of body melanization was evident
      from the analysis of assorted darker and lighter flies (from a mass culture of D.
      nepalensis reared at 21 degrees C) which lacked differences in dry mass but
      showed differences in desiccation survival hours and rate of water loss. For
      adult acclimation, we found a slight increase in desiccation resistance of flies
      reared at lower growth temperature, whereas in flies reared at 25 degrees C such
      a response was lacking. In D. nepalensis, greater developmental plasticity is
      consistent with its contrasting levels of seasonal abundance. Finally, in the
      context of global climate change in the Western Himalayas, D. nepalensis seems
      vulnerable in the warmer season due to lower adult as well as developmental
      acclimation potential at higher growth temperature (25 degrees C). 

PMID- 24923312
TI  - Welcome editorial: Change and continuity in Phonetica.

PMID- 24923313
TI  - Perceptual assimilation and discrimination of non-native vowel contrasts.
AB  - Research on language-specific tuning in speech perception has focused mainly on
      consonants, while that on non-native vowel perception has failed to address
      whether the same principles apply. Therefore, non-native vowel perception was
      investigated here in light of relevant theoretical models: the Perceptual
      Assimilation Model (PAM) and the Natural Referent Vowel (NRV) framework. American
      English speakers completed discrimination and native language assimilation
      (categorization and goodness rating) tests on six nonnative vowel contrasts.
      Discrimination was consistent with PAM assimilation types, but asymmetries
      predicted by NRV were only observed for single-category assimilations, suggesting
      that perceptual assimilation might modulate the effects of vowel peripherality on
      non-native vowel perception.

PMID- 24923314
TI  - On some quantitative properties of Czech r in newsreading.
AB  - This research examines the distributional characteristics of Czech r in terms of
      the number of contacts (periods). The traditional claim that this consonant is
      produced with two or more contacts is challenged by the empirical evidence of r
      realized in connected speech (newsreading style). The results of the study show
      that the most common variant of the (r) variable is a one-contact alveolar sound,
      with the multiple-contact realization of r being extremely rare. The role of
      eight linguistic variables is assessed in order to find out which factors are
      most likely to influence the number of contacts of Czech r. Some questions are
      discussed concerning its current definition as a trill.

PMID- 24923315
TI  - The 'whistled' fricative in Xitsonga: its articulation and acoustics.
AB  - The present study examines the articulation and acoustics of the typologically
      rare and understudied 'whistled' fricative sound in Xitsonga, a Southern Bantu
      language. Using ultrasound imaging and video recording, we examine the lingual
      and labial articulation of the whistled fricative. For the acoustic analysis, we
      employ the multitaper spectral analysis, which ensures reliable spectral
      estimates. The results revealed an interplay between multiple articulators
      involved in the production of the sound: the retroflex lingual gesture and the
      narrowing of the lower lip toward the upper teeth. Acoustically, the spectra of
      the whistled fricative are more peaked and compact than the acoustically similar
      palatoalveolar fricative, and the differences manifest themselves most clearly in
      two acoustic parameters, dynamic amplitude (Ad) and M2 (variance). The acoustic
      differences are also manifested in F2 and F3 in the surrounding vowels.
      Additionally, the 'whistled' fricative in Xitsonga is not quite whistled,
      contrary to the label given to the sound in previous studies. Building on the
      current articulatory and acoustic results, we discuss two different aerodynamic
      models for the whistled fricatives in Southern Bantu languages and conclude that
      the whistled fricative in Xitsonga is best characterized as a retroflex segment
      accompanied by weak whistling.

PMID- 24923317
TI  - Cluster synchronization and isolated desynchronization in complex networks with
      symmetries.
AB  - Synchronization is of central importance in power distribution,
      telecommunication, neuronal and biological networks. Many networks are observed
      to produce patterns of synchronized clusters, but it has been difficult to
      predict these clusters or understand the conditions under which they form. Here
      we present a new framework and develop techniques for the analysis of network
      dynamics that shows the connection between network symmetries and cluster
      formation. The connection between symmetries and cluster synchronization is
      experimentally confirmed in the context of real networks with heterogeneities and
      noise using an electro-optic network. We experimentally observe and theoretically
      predict a surprising phenomenon in which some clusters lose synchrony without
      disturbing the others. Our analysis shows that such behaviour will occur in a
      wide variety of networks and node dynamics. The results could guide the design of
      new power grid systems or lead to new understanding of the dynamical behaviour of
      networks ranging from neural to social. 

PMID- 24923319
TI  - Geometric facial gender scoring: objectivity of perception.
AB  - Gender score is the cognitive judgement of the degree of masculinity or
      femininity of a face which is considered to be a continuum. Gender scores have
      long been used in psychological studies to understand the complex psychosocial
      relationships between people. Perceptual scores for gender and attractiveness
      have been employed for quality assessment and planning of cosmetic facial
      surgery. Various neurological disorders have been linked to the facial structure
      in general and the facial gender perception in particular. While, subjective
      gender scoring by human raters has been a tool of choice for psychological
      studies for many years, the process is both time and resource consuming. In this
      study, we investigate the geometric features used by the human cognitive system
      in perceiving the degree of masculinity/femininity of a 3D face. We then propose
      a mathematical model that can mimic the human gender perception. For our
      experiments, we obtained 3D face scans of 64 subjects using the 3dMDface scanner.
      The textureless 3D face scans of the subjects were then observed in different
      poses and assigned a gender score by 75 raters of a similar background. Our
      results suggest that the human cognitive system employs a combination of
      Euclidean and geodesic distances between biologically significant landmarks of
      the face for gender scoring. We propose a mathematical model that is able to
      automatically assign an objective gender score to a 3D face with a correlation of
      up to 0.895 with the human subjective scores. 

PMID- 24923320
TI  - Trends in the aggressiveness of end-of-life care for Korean pediatric cancer
      patients who died in 2007-2010.
AB  - BACKGROUND: In light of the Korean Supreme Court's 2009 ruling favoring a
      patient's right to die with dignity, we evaluated trends in aggressive care in a
      cohort of pediatric cancer patients. Methods We conducted a population-based
      retrospective study that used administrative data for patients who died in 2007
      2010 among the 5,203 pediatric cancer patients registered at the Korean Cancer
      Central Registry (KCCR) during 2007-2009. RESULTS: In the time period covered,
      696 patients died. The proportion who had received chemotherapy in the last 30
      days of life decreased from 58.1% to 28.9% (P<0.001), those who received new
      chemotherapy in the same time period decreased from 55.2% to 15.1% (P<0.001), and
      those who received treatment in the last 2 weeks of life decreased from 51.4% to
      21.7% (P<0.001). In the last 30 days of life, the proportion of patients whose
      hospital admission period was over 14 days increased from 70.5% to 82.5% (P =
      0.03), the proportion who received cardiopulmonary resuscitation decreased from
      28.6% to 9.6% (P<0.001), and we found no statistically significant trends in the
      proportion of emergency department visits, intensive care unit admissions, or
      mechanical ventilation. CONCLUSIONS: In this study, in contrast with earlier
      ones, the aggressiveness of end-of-life care of Korean pediatric cancer patients
      decreased dramatically.

PMID- 24923321
TI  - Kisspeptin regulation of genes involved in cell invasion and angiogenesis in
      first trimester human trophoblast cells.
AB  - The precise regulation of extravillous trophoblast invasion of the uterine wall
      is a key process in successful pregnancies. Kisspeptin (KP) has been shown to
      inhibit cancer cell metastasis and placental trophoblast cell migration. In this
      study primary cultures of first trimester human trophoblast cells have been
      utilized in order to study the regulation of invasion and angiogenesis-related
      genes by KP. Trophoblast cells were isolated from first trimester placenta and
      their identity was confirmed by immunostaining for cytokeratin-7. Real-time
      quantitative RT-PCR demonstrated that primary trophoblast cells express higher
      levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line
      HTR8Svneo. Furthermore, trophoblast cells also expressed higher GPR54 and KP
      protein levels. Treating primary trophoblast cells with KP induced ERK1/2
      phosphorylation, while co-treating the cells with a KP antagonist almost
      completely blocked the activation of ERK1/2 and demonstrated that KP through its
      cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the
      migratory capability of trophoblast cells in a scratch-migration assay. Real-time
      quantitative RT-PCR demonstrated that KP treatment reduced the expression of
      matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the
      expression of tissue inhibitors of metalloproteinases 1 and 3. These results
      suggest that KP can inhibit first trimester trophoblast cells invasion via
      inhibition of cell migration and down regulation of the metalloproteinase system
      and VEGF-A. 

PMID- 24923322
TI  - Transposable element dynamics among asymbiotic and ectomycorrhizal Amanita fungi.
AB  - Transposable elements (TEs) are ubiquitous inhabitants of eukaryotic genomes and
      their proliferation and dispersal shape genome architectures and diversity.
      Nevertheless, TE dynamics are often explored for one species at a time and are
      rarely considered in ecological contexts. Recent work with plant pathogens
      suggests a link between symbiosis and TE abundance. The genomes of pathogenic
      fungi appear to house an increased abundance of TEs, and TEs are frequently
      associated with the genes involved in symbiosis. To investigate whether this
      pattern is general, and relevant to mutualistic plant-fungal symbioses, we
      sequenced the genomes of related asymbiotic (AS) and ectomycorrhizal (ECM)
      Amanita fungi. Using methods developed to interrogate both assembled and
      unassembled sequences, we characterized and quantified TEs across three AS and
      three ECM species, including the AS outgroup Volvariella volvacea. The ECM
      genomes are characterized by abundant numbers of TEs, an especially prominent
      feature of unassembled sequencing libraries. Increased TE activity in ECM species
      is also supported by phylogenetic analysis of the three most abundant TE
      superfamilies; phylogenies revealed many radiations within contemporary ECM
      species. However, the AS species Amanita thiersii also houses extensive
      amplifications of elements, highlighting the influence of additional evolutionary
      parameters on TE abundance. Our analyses provide further evidence for a link
      between symbiotic associations among plants and fungi, and increased TE activity,
      while highlighting the importance individual species' natural histories may have
      in shaping genome architecture. 

PMID- 24923323
TI  - The extent of genome flux and its role in the differentiation of bacterial
      lineages.
AB  - Horizontal gene transfer (HGT) and gene loss are key processes in bacterial
      evolution. However, the role of gene gain and loss in the emergence and
      maintenance of ecologically differentiated bacterial populations remains an open
      question. Here, we use whole-genome sequence data to quantify gene gain and loss
      for 27 lineages of the plant-associated bacterium Pseudomonas syringae. We apply
      an extensive error-control procedure that accounts for errors in draft genome
      data and greatly improves the accuracy of patterns of gene occurrence among these
      genomes. We demonstrate a history of extensive genome fluctuation for this
      species and show that individual lineages could have acquired thousands of genes
      in the same period in which a 1% amino acid divergence accrues in the core
      genome. Elucidating the dynamics of genome fluctuation reveals the rapid turnover
      of gained genes, such that the majority of recently gained genes are quickly
      lost. Despite high observed rates of fluctuation, a phylogeny inferred from
      patterns of gene occurrence is similar to a phylogeny based on amino acid
      replacements within the core genome. Furthermore, the core genome phylogeny
      suggests that P. syringae should be considered a number of distinct species, with
      levels of divergence at least equivalent to those between recognized bacterial
      species. Gained genes are transferred from a variety of sources, reflecting the
      depth and diversity of the potential gene pool available via HGT. Overall, our
      results provide further insights into the evolutionary dynamics of genome
      fluctuation and implicate HGT as a major factor contributing to the
      diversification of P. syringae lineages. 

PMID- 24923324
TI  - Pangenome evidence for extensive interdomain horizontal transfer affecting
      lineage core and shell genes in uncultured planktonic thaumarchaeota and
      euryarchaeota.
AB  - Horizontal gene transfer (HGT) is an important force in evolution, which may
      lead, among other things, to the adaptation to new environments by the import of
      new metabolic functions. Recent studies based on phylogenetic analyses of a few
      genome fragments containing archaeal 16S rRNA genes and fosmid-end sequences from
      deep-sea metagenomic libraries have suggested that marine planktonic archaea
      could be affected by high HGT frequency. Likewise, a composite genome of an
      uncultured marine euryarchaeote showed high levels of gene sequence similarity to
      bacterial genes. In this work, we ask whether HGT is frequent and widespread in
      genomes of these marine archaea, and whether HGT is an ancient and/or recurrent
      phenomenon. To answer these questions, we sequenced 997 fosmid archaeal clones
      from metagenomic libraries of deep-Mediterranean waters (1,000 and 3,000 m depth)
      and built comprehensive pangenomes for planktonic Thaumarchaeota (Group I
      archaea) and Euryarchaeota belonging to the uncultured Groups II and III
      Euryarchaeota (GII/III-Euryarchaeota). Comparison with available reference
      genomes of Thaumarchaeota and a composite marine surface euryarchaeote genome
      allowed us to define sets of core, lineage-specific core, and shell gene ortholog
      clusters for the two archaeal lineages. Molecular phylogenetic analyses of all
      gene clusters showed that 23.9% of marine Thaumarchaeota genes and 29.7% of
      GII/III-Euryarchaeota genes had been horizontally acquired from bacteria. HGT is
      not only extensive and directional but also ongoing, with high HGT levels in
      lineage-specific core (ancient transfers) and shell (recent transfers) genes.
      Many of the acquired genes are related to metabolism and membrane biogenesis,
      suggesting an adaptive value for life in cold, oligotrophic oceans. We
      hypothesize that the acquisition of an important amount of foreign genes by the
      ancestors of these archaeal groups significantly contributed to their divergence
      and ecological success. 

PMID- 24923325
TI  - The genome of the fungal-interactive soil bacterium Burkholderia terrae BS001-a
      plethora of outstanding interactive capabilities unveiled.
AB  - Burkholderia terrae strain BS001, obtained as an inhabitant of the mycosphere of
      Laccaria proxima (a close relative of Lyophyllum sp. strain Karsten), actively
      interacts with Lyophyllum sp. strain Karsten. We here summarize the remarkable
      ecological behavior of B. terrae BS001 in the mycosphere and add key data to
      this. Moreover, we extensively analyze the approximately 11.5-Mb five-replicon
      genome of B. terrae BS001 and highlight its remarkable features. Seventy-nine
      regions of genomic plasticity (RGP), that is, 16.48% of the total genome size,
      were found. One 70.42-kb RGP, RGP76, revealed a typical conjugal element
      structure, including a full type 4 secretion system. Comparative analyses across
      24 related Burkholderia genomes revealed that 95.66% of the total BS001 genome
      belongs to the variable part, whereas the remaining 4.34% constitutes the core
      genome. Genes for biofilm formation and several secretion systems, under which a
      type 3 secretion system (T3SS), were found, which is consistent with the
      hypothesis that T3SSs play a role in the interaction with Lyophyllum sp. strain
      Karsten. The high number of predicted metabolic pathways and membrane
      transporters suggested that strain BS001 can take up and utilize a range of
      sugars, amino acids and organic acids. In particular, a unique glycerol uptake
      system was found. The BS001 genome further contains genetic systems for the
      degradation of complex organic compounds. Moreover, gene clusters encoding
      nonribosomal peptide synthetases (NRPS) and hybrid polyketide synthases/NRPS were
      found, highlighting the potential role of secondary metabolites in the ecology of
      strain BS001. The patchwork of genetic features observed in the genome is
      consistent with the notion that 1) horizontal gene transfer is a main driver of
      B. terrae BS001 adaptation and 2) the organism is very flexible in its ecological
      behavior in soil. 

PMID- 24923326
TI  - Impacts of pretranscriptional DNA methylation, transcriptional transcription
      factor, and posttranscriptional microRNA regulations on protein evolutionary
      rate.
AB  - Gene expression is largely regulated by DNA methylation, transcription factor
      (TF), and microRNA (miRNA) before, during, and after transcription, respectively.
      Although the evolutionary effects of TF/miRNA regulations have been widely
      studied, evolutionary analysis of simultaneously accounting for DNA methylation,
      TF, and miRNA regulations and whether promoter methylation and gene body (coding
      regions) methylation have different effects on the rate of gene evolution remain
      uninvestigated. Here, we compared human-macaque and human-mouse protein
      evolutionary rates against experimentally determined single base-resolution DNA
      methylation data, revealing that promoter methylation level is positively
      correlated with protein evolutionary rates but negatively correlated with
      TF/miRNA regulations, whereas the opposite was observed for gene body methylation
      level. Our results showed that the relative importance of these regulatory
      factors in determining the rate of mammalian protein evolution is as follows:
      Promoter methylation ~ miRNA regulation > gene body methylation > TF regulation,
      and further indicated that promoter methylation and miRNA regulation have a
      significant dependent effect on protein evolutionary rates. Although the
      mechanisms underlying cooperation between DNA methylation and TFs/miRNAs in gene
      regulation remain unclear, our study helps to not only illuminate the impact of
      these regulatory factors on mammalian protein evolution but also their intricate
      interaction within gene regulatory networks. 

PMID- 24923327
TI  - Evolutionary origin and methylation status of human intronic CpG islands that are
      not present in mouse.
AB  - Imprinting of the human RB1 gene is due to the presence of a differentially
      methylated CpG island (CGI) in intron 2, which is part of a retrocopy derived
      from the PPP1R26 gene on chromosome 9. The murine Rb1 gene does not have this
      retrocopy and is not imprinted. We have investigated whether the RB1/Rb1 locus is
      unique with respect to these differences. For this, we have compared the CGIs
      from human and mouse by in silico analyses. We have found that the human genome
      does not only contain more CGIs than the mouse, but the proportion of intronic
      CGIs is also higher (7.7% vs. 3.5%). At least 2,033 human intronic CGIs are not
      present in the mouse. Among these CGIs, 104 show sequence similarities elsewhere
      in the human genome, which suggests that they arose from retrotransposition. We
      could narrow down the time points when most of these CGIs appeared during
      evolution. Their methylation status was analyzed in two monocyte methylome data
      sets from whole-genome bisulfite sequencing and in 18 published methylomes. Four
      CGIs, which are located in the RB1, ASRGL1, PARP11, and PDXDC1 genes, occur as
      methylated and unmethylated copies. In contrast to imprinted methylation at the
      RB1 locus, differential methylation of the ASRGL1 and PDXDC1 CGIs appears to be
      sequence dependent. Our study supports the notion that the epigenetic fate of the
      retrotransposed DNA depends on its sequence and selective forces at the
      integration site. 

PMID- 24923328
TI  - Facile heterogenization of a cobalt catalyst via graphene adsorption: robust and
      versatile dihydrogen production systems.
AB  - A heterogeneous dihydrogen (H2) production system has been attained by simply
      soaking electrodes made from electro-deposited graphene on FTO plated glass in
      solutions of a cobalt bis(dithiolate) compound. The resulting electrodes are
      active in weakly acidic aqueous solutions (pH > 3), have relatively low
      overpotentials (0.37 V versus platinum), show high catalytic rates (TOF > 1000 s(
      1)), and are resistant to degradation by dioxygen. 

PMID- 24923329
TI  - Renalase gene polymorphism in patients after renal allograft transplantation.
AB  - BACKGROUND/AIMS: Renalase is a recently discovered protein, which is likely
      involved in regulation of blood pressure in humans and animals. Previous studies
      suggest that renalase reflects kidney functioning. A common missense polymorphism
      in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp)
      has been described. In this study we examined the association between (Glu37Asp)
      polymorphism (rs2296545) in renalase gene and kidney allograft function. METHODS:
      The study enrolled 270 Caucasian kidney allograft recipients. SNP within the
      renalase was genotyped using TaqMan genotyping assays. RESULTS: There were no
      statistically significant associations between renalase gene rs2296545
      polymorphism and delayed graft function, acute rejection, chronic allograft
      dysfunction as well as creatinine serum concentrations and blood pressure values
      after transplantation. CONCLUSIONS: The results of this study suggest, that
      renalase gene rs2296545 polymorphism is not important factor determining renal
      allograft function.

PMID- 24923331
TI  - Operationalizing the RE-AIM framework to evaluate the impact of multi-sector
      partnerships.
AB  - BACKGROUND: The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and
      Maintenance) framework is a reliable tool for the translation of research to
      practice. This framework has been widely applied to assess the impact of
      individual interventions. However, RE-AIM has rarely been used to evaluate
      implementation interventions, especially from multi-sector partnerships. The
      primary purpose of this paper is to operationalize the RE-AIM approach to
      evaluate large, multi-sector partnerships. SCI Action Canada, a community
      university partnership aimed to promote physical activity among adults with
      spinal cord injury, is used as an example. A secondary purpose is to provide
      initial data from SCI Action Canada by using this conceptualization of RE-AIM.
      METHODS: Each RE-AIM element is operationalized for multi-sector partnerships.
      Specific to SCI Action Canada, seven reach calculations, four adoption rates,
      four effectiveness outcomes, one implementation, one organizational maintenance,
      and two individual maintenance outcomes are defined. The specific numerators
      based on SCI Action Canada activities are also listed for each of these
      calculations. RESULTS: The results are derived from SCI Action Canada activities.
      SCI Action Canada's reach ranged from 3% (end-user direct national reach) to 37%
      (total regional reach). Adoption rates were 15% (provincial level adoption) to
      76% (regional level adoption). Implementation and organizational maintenance
      rates were 92% and 100%, respectively. CONCLUSIONS: We have operationalized the
      RE-AIM framework for larger multi-sectoral partnerships and demonstrated its
      applicability to such partnerships with SCI Action Canada. Future partnerships
      could use RE-AIM to assess their public health impact.

PMID- 24923330
TI  - Sequential combination of decitabine and idarubicin synergistically enhances anti
      leukemia effect followed by demethylating Wnt pathway inhibitor promoters and
      downregulating Wnt pathway nuclear target.
AB  - BACKGROUND: The methylation inhibitor 5-Aza-2'-deoxycytidine (decitabine, DAC)
      has a great therapeutic value for acute myeloid leukemia (AML) and
      myelodysplastic syndromes (MDS). But decitabine monotherapy was associated with a
      relatively low rate of complete remission in AML and MDS. We aimed to investigate
      the effect of several anti-leukemia drugs in combination with decitabine on the
      proliferation of myeloid leukemia cells, to select the most efficient combination
      group and explore the associated mechanisms of these combination therapies.
      METHODS: Cell proliferation was tested by MTT assay and CFU-GM assay. Cell
      apoptosis was evaluated by Annexin V and PI staining in cell culture, TUNEL assay
      and transmission electron microscopy in animal study. MicroPET was used to
      imaging the tumor in mouse model. Molecular studies were conducted using
      microarray expression analysis, which was used to explore associated pathways,
      and real-time quantitative reverse transcription-PCR, western blot and
      immunohistochemistry, used to assess regulation of Wnt/beta-catenin pathway.
      Statistical significance among groups was determined by one-way ANOVA analysis
      followed by post hoc Bonferroni's multiple comparison test. RESULTS: Among five
      anti-leukemia agents in combining with decitabine, the sequential combination of
      decitabine and idarubicin induced synergistic cell death in U937 cells, and this
      effect was verified in HEL, SKM-1 cells and AML cells isolated from AML patients.
      Importantly, tumor growth inhibition in this sequential combination was found to
      be higher than in single agent or controls in vivo. Moreover, sequential
      combination of the two agents induced apoptosis and depression of the Wnt/beta
      catenin pathway in both AML cell culture and animal studies. CONCLUSIONS: The
      findings demonstrated that sequentially combination of decitabine and idarubicin
      had synergistic anti-leukemia effects. These effects were mainly attributed to
      demethylation of Wnt/beta-catenin pathway inhibitors and downregulation of
      Wnt/beta-catenin pathway nuclear targets.

PMID- 24923332
TI  - Survivin inhibition via EZN-3042 in canine lymphoma and osteosarcoma.
AB  - Canine lymphoma (LSA) and osteosarcoma (OS) have high mortality rates and remain
      in need of more effective therapeutic approaches. Survivin, an inhibitor of
      apoptosis (IAP) family member protein that inhibits apoptosis and drives cell
      proliferation, is commonly elevated in human and canine cancer. Survivin
      expression is a negative prognostic factor in dogs with LSA and OS, and canine
      LSA and OS cell lines express high levels of survivin. In this study, we
      demonstrate that survivin downregulation in canine LSA and OS cells using a
      clinically applicable locked nucleic acid antisense oligonucleotide (EZN-3042,
      Enzon Pharmaceuticals, Piscataway Township, NJ, USA) inhibits growth, induces
      apoptosis and enhances chemosensitivity in vitro, and inhibits survivin
      transcription and protein production in orthotopic canine OS xenografts. Our
      findings strongly suggest that survivin-directed therapies might be effective in
      treatment of canine LSA and OS and support evaluation of EZN-3042 in dogs with
      cancer. 

PMID- 24923333
TI  - Are vitamin D levels affected by acute bacterial infections in children?
AB  - AIMS: Vitamin D deficiency is associated with infectious diseases; however, it is
      not known whether vitamin D levels are affected by acute infection. Our aim was
      to establish whether 25-hydroxyvitamin D (25OHD) levels taken during an acute
      bacterial infection are representative of baseline levels. METHODS: Thirty
      children between 6 months and 15 years of age with proven bacterial infections
      presenting to a tertiary paediatric referral centre had 25OHD levels taken during
      their acute infection and again 1 month later provided that they had recovered
      from their infection, had no subsequent infections and had not been taking
      vitamin supplements. 25OHD levels were measured by liquid chromatography mass
      spectrometry. RESULTS: Mean 25OHD at enrolment was 67.5 nmol/L (standard
      deviation (SD) 22.0), and mean 25OHD at 1 month follow up was 72.7 nmol/L (SD
      25.8) (paired t-test P = 0.25). C-reactive protein levels were recorded in 29/30
      patients at enrolment (mean 85.1 mg/L, SD 83.5) and 25/30 patients at follow-up
      (mean 4.0 mg/L, SD 3.3) (paired t-test P = 0.002). The ethnicity of the
      participants was New Zealand European or European Other, 26; Samoan, 2; Maori, 1;
      and Chinese, 1. CONCLUSIONS: In children, 25OHD levels are not affected by acute
      bacterial infections; 25OHD levels taken during acute bacterial infection are
      representative of baseline levels. 25OHD levels collected during acute bacterial
      infection provide reliable information for case-control studies.

PMID- 24923334
TI  - Caffeine and suicide: a systematic review.
AB  - Suicide is considered a deliberate act initiated and concluded by a person with
      full knowledge or expectation of a fatal result, and one of the main symptoms of
      depression. An individual's conscious and excessive ingestion of a damaging
      substance is also considered to be an attempted suicide. Despite limited
      knowledge of caffeine abuse, deaths from overdose of caffeine have been reported
      in the literature. Thus, this study aims to review the existing literature on
      caffeine consumption and suicide attempts and deaths, investigating the relation
      between caffeine consumption and suicide attempts and deaths. We found 24 studies
      that discuss the relationship between caffeine and suicide. The findings revealed
      that, despite being an addictive substance and potentially fatal in higher doses,
      caffeine was still a rare factor in a number of studies concerning its relation
      with suicide attempts and death. The majority of the research found in this study
      was of the case study type. Furthermore, the majority of studies focus on the
      assistance offered to the victim and the procedures undertaken to control the
      bodily damage created. The existing studies indicate the substance may act as
      either a direct or an indirect agent in suicide. Therefore, a better
      understanding of how caffeine may be linked to suicide is crucial for its
      prevention. 

PMID- 24923335
TI  - Deep brain stimulation: a new treatment in mood and anxiety disorders.
AB  - This article considered already existing studies about Deep Brain Stimulation in
      Mood and Anxiety Disorders. In particular, articles regarding Obsessive
      Compulsive Disorder and Major Depression were mostly analyzed, due to the lack of
      researches about other types of Mood and Anxiety Disorders. We have concentrated
      on the target areas where Deep Brain Stimulation was most commonly applied, and
      on the effects this measure had on treatment-refractory patients. The obtained
      results showed that the stimulation of the: nucleus accumbens, subgenual
      cingulate cortex and ventral capsule/ventral striatum, has a positive influence
      on the development of the disorders investigated, sometimes showing the complete
      remission of the symptoms. Although Deep Brain Stimulation was overall found to
      be a promising and safe treatment for Mood and Anxiety Disorders, there are not
      enough studies proving its efficacy in wide samples and in the presence of more
      complex variables. 

PMID- 24923336
TI  - Cytokine-induced depression: current status and novel targets for depression
      therapy.
AB  - Current treatments of depression include psychological, pharmacological and
      physical approaches. Pharmacological interventions to treat depression have
      previously focused on modifying dysfunctional neurotransmitter systems. Overall,
      these treatments have demonstrated an ability to manage major depression but
      otucomes continue to be poor in many patients, especially those with long term
      illness or with previous multiple relapses. This may be due to the fact that
      depression is a systemic and neuroprogressive illness involving multiple
      biological pathways such as immunological factors. There is substantial evidence
      that cytokine therapies induce depressive symptoms in clinical populations. The
      model of cytokine-induced depression has provided important information relative
      to the risk factors and biological pathways involved in the etiology of
      depressive symptoms and, most importantly, the identification and knowledge of
      these factors has allowed new treatment targets to be explored. When an exogenous
      cytokine such as interferon-alpha is administered, proinflammatory cytokines are
      activated, leading to alterations in neurotransmission and endocrine pathways and
      producing neurotoxicity. Several new treatments for depression acting through
      pathways other than amine neurotransmission have emerged in recent years. The
      regulation of the inflammatory response, the decrease in the activity of the
      hypothalamic-pituitary-adrenal axis and the prevention of neurotoxicity are
      potential targets for new drugs. Though these drugs are mostly at the proof-of
      concept stage, some of them have already shown promising results for the
      treatment of depression. 

PMID- 24923338
TI  - Current directions in non-invasive low intensity electric brain stimulation for
      depressive disorder.
AB  - Non-invasive stimulation of the human brain to improve depressive symptoms is
      increasingly finding its way in clinical settings as a viable form of somatic
      treatment. Following successful modulation of neural excitability with subsequent
      antidepressant effects, neural polarization by administrating weak direct
      currents to the scalp has gained renewed interest. A new wave of basic and
      clinical studies seems to underscore the potential therapeutic value of direct
      current stimulation in the treatment of depression. Issues concerning the lack of
      mechanistic insights into the workings of modifying brain function through neural
      polarization and how this process translates to its antidepressant properties
      calls for additional research. The range of its clinical applicability has yet to
      be established. 

PMID- 24923337
TI  - Neurological aspects of grief.
AB  - Despite grief being a universal experience and the increased scientific attention
      paid to grief and bereavement in recent years, studies that seek to better
      understand the role of the neurological aspects of grief are still scarce. We
      found 5 studies that discussed the relationship between the neurological aspects
      of grief due to the death of a loved one. All studies showed an activation of
      common areas, i.e., the anterior cingulate cortex (ACC), posterior cingulate
      cortex (PCC), prefrontal cortex (PFC), insula and amygdala. These findings could
      indicate that there is a group of areas working together and responding to
      generate the symptomatology of grief. Because grief is a universal experience, it
      is essential that the necessary and effective support can be provided to those
      who experience the loss of someone considered important in their lives, and this
      requires understanding grief's manifestation, its differential diagnosis in
      reference to other clinical conditions, mainly psychiatric ones, and adequate
      forms of intervention and treatment when necessary. Proper understanding and
      support can help prevent the emergence of more serious health problems. 

PMID- 24923339
TI  - Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical
      compound of Cannabis sativa.
AB  - Anxiety and depression are pathologies that affect human beings in many aspects
      of life, including social life, productivity and health. Cannabidiol (CBD) is a
      constituent non-psychotomimetic of Cannabis sativa with great psychiatric
      potential, including uses as an antidepressant-like and anxiolytic-like compound.
      The aim of this study is to review studies of animal models using CBD as an
      anxiolytic-like and antidepressant-like compound. Studies involving animal
      models, performing a variety of experiments on the above-mentioned disorders,
      such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel
      conflict test (VCT), suggest that CBD exhibited an anti-anxiety and
      antidepressant effects in animal models discussed. Experiments with CBD
      demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies
      demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor. 

PMID- 24923340
TI  - Depression as a comorbidity in Behcet's syndrome.
AB  - Behcet's syndrome (BD) is a controversial, chronic, and episodic condition that
      is autoimmune in origin and causes systemic vasculitis in the arteries and
      genital veins. BD is consistently associated with depression, with an incidence
      of 86% upon the first appearance of symptoms and disorders of the disease.
      However, few studies have looked at depression and other psychiatric disorders,
      such as anxiety, in the context of comorbidity with BD. The aim of this review is
      to identify articles that focus on the relation between BD and depression as a
      comorbidity. The studies found revealed a consistently high incidence of
      depression in the BD population, even when compared with other chronic
      pathologies including Rheumatoid Arthritis and Psoriasis, although there was a
      limitation in the use of scales and other tools for assessment and control of
      comorbid symptoms, moreover there are no studies linking the drugs used in the BD
      treatment of each patient and the symptoms present in each case. This review
      clearly shows the lack of research in which depression scores are analyzed in
      relation to the medications used by individual patients. Additionally, the use of
      additional scales is necessary to increase the knowledge about the nature and
      consequences of depression as comorbidity of BD. 

PMID- 24923341
TI  - Panic and the brainstem: clues from neuroimaging studies.
AB  - One of the most influential theories has conceived unexpected panic attack (PA)
      as a primal defensive reaction to threat within the internal milieu of the body.
      This theory is based on findings suggesting the involvement of dysfunctional
      respiratory regulation and/or abnormally sensitive central neural network of
      carbon dioxide (CO2)/hydrogen ion (H<sup>+</sup>) chemoreception in PA. Thus,
      unexpected PA may be related to phylogenetically older brain structures,
      including the brainstem areas, which process basic functions related to the
      organism's internal milieu. The brainstem represents a crucial area for
      homeostatic regulation, including chemoreception and cardio-respiratory control.
      In addition, the midbrain dorsal periaqueductal gray may be involved in the
      unconditioned defense reactions to proximal threats, including internal physical
      stimuli. Our aim was to specifically consider the potential involvement of the
      brainstem in panic disorder (PD) by a comprehensive review of the available
      neuroimaging studies. Available data are limited and potentially affected by
      several limitations. However, preliminary evidence of a role of the brainstem in
      PD can be found and, secondly, the brainstem serotonergic system seems to be
      involved in panic modulation with indications of both altered serotonergic
      receptors and 5-HT transporter bindings. In conclusion, our review suggests that
      the brainstem may be involved in psychopathology of PD and supports the relevant
      role of subcortical serotonergic system in panic pathogenesis. 

PMID- 24923342
TI  - Bupropion in the depression-related sexual dysfunction: a systematic review.
AB  - Depression is the most prevalent psychiatric disorder (16.6%) and is frequently
      associated with impairments in several areas. Sexual dysfunction (SD) is a
      prevalent problem with rates ranging from 40-45% in adult women and 20- 30% in
      adult men. A relationship between depression and sexual dysfunction has been
      shown in the literature although the mechanisms of this association are not yet
      clear. Many antidepressants, especially selective serotonin reuptake inhibitors
      (SSRIs), list sexual dysfunction as a side effect. New drug alternatives with
      fewer side effects have been proposed, and bupropion is one of them. This study
      aims to review the literature on bupropion and its impact in sexual function on
      depressed subjects. Most of the studies have noted that bupropion is not only as
      effective as other antidepressants but has the advantage of a lower impact on
      sexual functioning. Some other studies have found that bupropion can even enhance
      sexual function in certain individuals. Bupropion is also effective, when
      combined with other antidepressants, in treating emergent sexual dysfunction.
      Bupropion may be an alternative treatment for depression that does not include
      the sexual side effects associated with most of the prescribed antidepressants
      available; however, additional research is required. 

PMID- 24923343
TI  - Repetitive transcranial magnetic stimulation (rTMS) to treat refractory panic
      disorder patient: a case report.
AB  - Panic disorder (PD) is an anxiety disorder that is highly disruptive to the
      patient's life and needs new options for effective treatments. In this case
      report, we present an application of repetitive transcranial magnetic stimulation
      (rTMS) in a refractory patient resistant to cognitive behavior therapy (CBT) and
      pharmacotherapy who was treated with a combined protocol of rTMS with a
      sequential stimulation of right and left dorsolateral prefrontal cortex (DLPFC).
      The protocol was conducted 3 times per week during 4 weeks, with one month follow
      up. The fact that the patient showed improvement suggests that rTMS can be an
      effective option of treatment. 

PMID- 24923344
TI  - Nicotine effects on human affective functions: a systematic review of the
      literature on a controversial issue.
AB  - The observation that nicotine modulates negative affectivity and has a mood
      enhancing effect mainly derives from studies conducted in the general population
      and in clinical samples, mostly in nicotine-deprived subjects. It has been
      explained by the so called deprivation-reversal hypothesis (i.e., nicotine
      modulates affect because it alleviates withdrawal symptoms). However,
      experimental studies suggest that nicotine might modulate different affective
      functions (e.g., aggressiveness, anxiety) and exert a direct modulating effect on
      human affectivity. The present paper is a systematic review of the literature
      aiming at verifying this second hypothesis. A computerized search was carried out
      (PubMed/Medline 1960-2012). Inclusion criteria were: 1. English language papers
      published in peer-reviewed journals; 2. experimental/quasi experimental design
      studies; 3. no deprived adults; 4. inclusion of a control condition; 5. no
      additional Axis I or II psychiatric disorders. Twenty-one papers met our
      inclusion criteria. Nicotine was showed to alleviate depression both in smokers
      and non-smokers, especially if depressed or vulnerable to depression. This effect
      seemed related to the activation of the dopaminergic brain rewarding system. No
      clear effect on anxiety was found. Nicotine, thus, seems to exert a direct
      modulating effect on human mood. Possible limitations of the reviewed studies and
      future research directions are proposed. 

PMID- 24923345
TI  - Psychosocial stress but not exercise increases cortisol and reduces state anxiety
      levels in school classes - results from a stressor applicable in large group
      settings.
AB  - Both, psychosocial stress and exercise in the past have been used as stressors to
      elevate saliva cortisol and change state anxiety levels. In the present study,
      high-school students at the age of 14 were randomly assigned to three
      experimental groups: (1) an exercise group (n = 18), that was running 15 minutes
      at a medium intensity level of 65-75% HRmax, (2) a psychosocial stress group (n =
      19), and (3) a control group (n = 18). The psychosocial stress was induced to the
      students by completing a standardized intelligence test under the assumption that
      their IQ scores would be made public in class. Results display that only
      psychosocial stress but not exercise was able to significantly increase cortisol
      levels but decreased cognitive state anxiety in adolescents. The psychosocial
      stress protocol applied here is proposed for use in future stress studies with
      children or adolescents in group settings, e.g., in school. 

PMID- 24923346
TI  - Effects of exercise on anxiety and depression disorders: review of meta- analyses
      and neurobiological mechanisms.
AB  - Anxiety and depression are the most frequently diagnosed psychological diseases
      showing a high co-morbidity. They have a severe impact on the lives of the
      persons concerned. Many meta-analytical studies suggested a positive anxiolytic
      and depression-reducing effect of exercise programs. The aim of the present
      article is to synthesize metaanalyses on the effects of exercise on anxiety and
      depression and to describe average effect sizes. For this purpose 37 meta
      analyses were included reporting 50 effect sizes for anxiety scores of 42,264
      participants and depression scores of 48,207 persons. The average documented
      anxiolytic effect of exercise in these reviews was small, 0.34. In contrast, the
      effect of exercise on depression was significantly higher and at a moderate
      level, 0.56. Data of randomized controlled trials suggest higher sizes for the
      effect of exercise on anxiety and depression leading to increases up to moderate
      and large effects, respectively. Additionally, exercise seems to be more
      beneficial for patients compared to participants within a non-clinical, normal
      range of psychological disease. Especially for the effect of exercise on anxiety,
      more high quality meta-analyses of randomized controlled trials are needed.
      Finally, possible neurobiological explanations are suggested for the positive
      effect of exercise on psychological disorders like anxiety and depression. 

PMID- 24923347
TI  - Executive function impairments in patients with depression.
AB  - Depression, the most prevalent psychiatric disorder, has a lifelong risk of 20%
      and is related to high rates of death among the patients. Thus, this study aims
      to conduct a systematic review of changes in executive functions of adult
      patients diagnosed with depression. We found 1381 articles; however, only 28 were
      selected and recovered. The inclusion criteria was the assessment of executive
      functions with at least one neuropsychological test, and articles that evaluated
      primarily adult individuals with depression, without comparison to other
      psychiatric disorders. Although most of the studies (25 out of 28 analyzed) have
      shown deficits in some executive subcomponents, these findings are not conclusive
      because they used different parameters of assessment. Moreover, many variables
      were not controlled, such as the different subtypes of the disorder, the high
      level of severity, comorbidity and the use of drugs. Most studies showed
      different deficits in executive functions in depressed patients, but further
      longitudinal studies are needed in order to confirm these findings. 

PMID- 24923348
TI  - Chest pain, panic disorder and coronary artery disease: a systematic review.
AB  - Chest pain may be due benign diseases but often suggests an association with
      coronary artery disease, which justifies a quick search for medical care.
      However, some people have anxiety disorder with symptoms that resemble clearly an
      acute coronary syndrome. More specifically, during a panic attack an abrupt
      feeling of fear accompanied by symptoms such as breathlessness, palpitations and
      chest pain, makes patients believe they have a heart attack and confuse
      physicians about the diagnosis. The association between panic disorder and
      coronary artery disease has been extensively studied in recent years and,
      although some studies have shown anxiety disorders coexisting or increasing the
      risk of heart disease, one causal hypothesis is still missing. The aim of this
      systematic review is to present the various ways in which the scientific
      community has been investigating the relation between chest pain, panic disorder
      and coronary artery disease. 

PMID- 24923349
TI  - Current pharmacological interventions in panic disorder.
AB  - The aim of this review was to summarize the recent evidences regarding the
      pharmacological treatment of panic disorder (PD). The authors performed a review
      of the literature regarding the pharmacological treatment of PD since the year
      2000. The research done in the last decade brought strong evidences of
      effectiveness for paroxetine, venlafaxine, sertraline, fluvoxamine, citalopram,
      fluoxetine, clonazepam, and the relatively novel agent escitalopram. There are
      evidences indicating that the other new compounds inositol, duloxetine,
      mirtazapine, milnacipran, and nefazodone have antipanic properties and may be
      effective compounds in the treatment of PD. The effectiveness of reboxetine and
      anticonvulsants is a subject of controversy. In addition to selective serotonin
      reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors,
      tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines and
      atypical antipsychotics may be valid alternatives in the treatment of PD. Recent
      data indicate that augmentation strategies with aripiprazole, olanzapine,
      pindolol or clonazepam may be effective. D-cycloserine is a promising agent in
      the augmentation of cognitive behavioral therapy. 

PMID- 24923350
TI  - Acute effects of exercise on mood and EEG activity in healthy young subjects: a
      systematic review.
AB  - Electroencephalography has been used to establish the relationship among cortical
      activity, exercise and mood, such as asymmetry, absolute and relative power. The
      purpose of this study was to systematically review the influence of cortical
      activity on mood state induced by exercise. The Preferred Reporting Items in
      Systematic reviews and Meta-Analyses was followed in this study. The studies were
      retrieved from MEDLINE/PubMed, ISI Web of Knowledge and SciELO. Search was
      conducted in all databases using the following terms: EEG asymmetry, sLORETA,
      exercise, with affect, mood and emotions. Based on the defined criteria, a total
      of 727 articles were found in the search conducted in the literature (666 in
      Pubmed, 54 in ISI Web of Science, 2 in SciELO and 5 in other data sources). Total
      of 11 studies were selected which properly met the criteria for this review. Nine
      out of 11 studies used the frontal asymmetry, four used absolute and relative
      power and one used sLORETA. With regard to changes in cortical activity and mood
      induced by exercise, six studies attributed this result to different intensities,
      one to duration, one to type of exercise and one to fitness level. In general,
      EEG measures showed contradictory evidence of its ability to predict or modulate
      psychological mood states through exercise intervention. 

PMID- 24923351
TI  - Neuroimaging correlates of pharmacological and psychological treatments for
      specific phobia.
AB  - Specific phobia is an anxiety disorder characterized by irrational fear and
      avoidance of specific things or situations, interfering significantly with the
      patients' daily life. Treatment for the disorder consists of both pharmacological
      and psychological approaches, mainly cognitive behavioral therapy (CBT).
      Neuroimaging techniques have been used in an attempt to improve our understanding
      of the neurobiology of SP and of the effects of treatment options available. This
      review describes the design and results of eight articles investigating the
      neuroimaging correlates of pharmacological and psychological treatments for SP.
      The studies show that CBT is effective in SP, leading to a reduction of anxiety
      symptoms that is accompanied by functional alterations in the brain. The results
      of pharmacological interventions for SP are less uniform, but suggest that the
      partial agonist of the NMDA (N-methyl D-aspartate) receptor DCS (D-cycloserine)
      can be used in combination with psychotherapy techniques for the achievement of
      quicker treatment response and that DCS modulates the function of structures
      implicated in the neurobiology of SP. Further research should explore the
      augmentation of CBT treatment with DCS in controlled trials. 

PMID- 24923352
TI  - Disseminated giant hyperkeratotic porokeratosis and treatment with acitretin: a
      case report.

PMID- 24923354
TI  - Putative roles of Ca(2+) -independent phospholipase A2 in respiratory chain
      associated ROS production in brain mitochondria: influence of docosahexaenoic
      acid and bromoenol lactone.
AB  - Ca(2+) -independent phospholipase A2 (iPLA2 ) is hypothesized to control
      mitochondrial reactive oxygen species (ROS) generation. Here, we modulated the
      influence of iPLA2 -induced liberation of non-esterified free fatty acids on ROS
      generation associated with the electron transport chain. We demonstrate enzymatic
      activity of membrane-associated iPLA2 in native, energized rat brain mitochondria
      (RBM). Theoretically, enhanced liberation of free fatty acids by iPLA2 modulates
      mitochondrial ROS generation, either attenuating the reversed electron transport
      (RET) or deregulating the forward electron transport of electron transport chain.
      For mimicking such conditions, we probed the effect of docosahexaenoic acid
      (DHA), a major iPLA2 product on ROS generation. We demonstrate that the adenine
      nucleotide translocase partly mediates DHA-induced uncoupling, and that low
      micromolar DHA concentrations diminish RET-dependent ROS generation. Uncoupling
      proteins have no effect, but the adenine nucleotide translocase inhibitor
      carboxyatractyloside attenuates DHA-linked uncoupling effect on RET-dependent ROS
      generation. Under physiological conditions of forward electron transport, low
      micromolar DHA stimulates ROS generation. Finally, exposure of RBM to the iPLA2
      inhibitor bromoenol lactone (BEL) enhanced ROS generation. BEL diminished RBM
      glutathione content. BEL-treated RBM exhibits reduced Ca(2+) retention capacity
      and partial depolarization. Thus, we rebut the view that iPLA2 attenuates
      oxidative stress in brain mitochondria. However, the iPLA2 inhibitor BEL has
      detrimental activities on energy-dependent mitochondrial functions. The Ca(2+) 
      independent phospholipase A2 (iPLA2 ), a FFA (free fatty acids)-generating
      membrane-attached mitochondrial phospholipase, is potential to regulate ROS
      (reactive oxygen species) generation by mitochondria. FFA can either decrease
      reversed electron transport (RET)-linked or enhance forward electron transport
      (FET)-linked ROS generation. In the physiological mode of FET, iPLA2 activity
      increases ROS generation. The iPLA2 inhibitor BEL exerts detrimental effects on
      energy-dependent mitochondrial functions. 

PMID- 24923353
TI  - 14-3-3sigma induces heat shock protein 70 expression in hepatocellular carcinoma.
AB  - BACKGROUND: 14-3-3sigma is implicated in promoting tumor development of various
      malignancies. However, the clinical relevance of 14-3-3sigma in hepatocellular
      carcinoma (HCC) tumor progression and modulation and pathway elucidation remain
      unclear. METHODS: We investigated 14-3-3sigma expression in 109 HCC tissues by
      immunohistochemistry. Overexpression and knockdown experiments were performed by
      transfection with cDNA or siRNA. Protein expression and cell migration were
      determined by Western blot and Boyden chamber assay. RESULTS: In this study, we
      found that 14-3-3sigma is abundantly expressed in HCC tumors. Stable or transient
      overexpression of 14-3-3sigma induces the expression of heat shock factor-1alpha
      (HSF-1alpha) and heat shock protein 70 (HSP70) in HCC cells. Moreover, expression
      of 14-3-3sigma significantly correlates with HSF-1alpha/HSP70 in HCC tumors and
      both 14-3-3sigma and HSP70 overexpression are associated with micro-vascular
      thrombi in HCC patients, suggesting that 14-3-3sigma/HSP70 expression is
      potentially involved in cell migration/invasion. Results of an in vitro migration
      assay indicate that 14-3-3sigma promotes cell migration and that 14-3-3sigma
      induced cell migration is impaired by siRNA knockdown of HSP70. Finally, 14-3
      3sigma-induced HSF-1alpha/HSP70 expression is abolished by the knockdown of beta
      catenin or activation of GSK-3beta. CONCLUSIONS: Our findings indicate that 14-3
      3sigma participates in promoting HCC cell migration and tumor development via
      beta-catenin/HSF-1alpha/HSP70 pathway regulation. Thus, 14-3-3sigma alone or
      combined with HSP70 are potential prognostic biomarkers for HCC.

PMID- 24923355
TI  - Polyethylene glycol compared with ytterbium oxide as a total faecal output marker
      to predict organic matter intake of dairy ewes fed indoors or at pasture.
AB  - Several external markers can be used for estimating total faecal output in view
      of assessing ruminant intake at pasture. Among them, ytterbium (Yb) has been used
      for many years in various conditions. Polyethylene glycol (PEG) is a promising
      external marker because it can be rapidly determined using near-infrared
      spectroscopy (NIRS). The study consisted of 24 adult lactating dairy ewes over
      three periods (P1, P2 and P3), fed with three different diets: P1, total mixed
      ration (TMR); P2, Italian ryegrass (IRG); and P3, pasture. After an adaptation
      period, the ewes were administered a daily dose of ytterbium oxide (0.35 g/day)
      and PEG (20 g/day) for 2 weeks. During the last week, the daily organic matter
      intake (OMIOBS) was measured. Faecal samples were collected at milking time (0800
      and 1600 h) to determine marker content, using only samples collected in the
      morning (PEGm) or by averaging samples (Yb, PEGma). Faecal marker content made it
      possible to assess total faecal output, either using the two recovery rates for
      PEG (0.98 or 0.87) or not. The OMIOBS was assessed on the basis of total faeces
      estimated with Yb (OMIYb) or PEG (OMIPEG), and the digestibility was calculated
      on the basis of feed analysis. With total TMR (P1), the OMIPEG, corrected with
      recovery rate (OMIPEGm98) or not corrected (OMIPEGm) was 2.40 kg/day and 2.50
      kg/day, respectively, and was not different (P>0.05) from OMIOBS (2.51 kg/day),
      whereas OMIYb was lower (2.14 kg/day) (P<0.001). With IRG (P2), OMIPEGm98 (1.67
      kg/day), OMIPEGm87 (1.51 kg/day) and OMIYb (1.59 kg/day) were not different
      (P>0.05) from OMIOBS (1.57 kg/day). With pasture (P3), the OMIPEGm (1.54 kg/day)
      and OMIPEGm98 (1.48 kg/day) were not different (P>0.05) from the OMI assessed
      from the biomass measurement (1.52 kg/day). The OMIYb (1.36 kg/day) was lower
      (P<0.05) but not different from OMIPEGm98 and OMIPEGm87. Spearman's rank
      correlation between OMIOBS and other OMIs (predicted with Yb or PEG P1 and P2)
      showed that it is possible to rank animals using PEG when there is a sufficiently
      wide range of OMIOBS (1.65 to 2.8 kg/day in P1) but not within a narrower range
      (1.47 to 1.72 kg/day in P2). In conclusion, the present study confirms that PEG
      is a valuable external faecal marker, easy to prepare (solution), administer and
      determine (NIRS). It can be used to assess intake with numerous animals at
      pasture, but only for groups, and not to quantitatively estimate individual OMI. 

PMID- 24923356
TI  - Osteoprotegerin in Turner syndrome - relationship to aortic diameter.
AB  - BACKGROUND: Cardiovascular disease is a cardinal trait of Turner syndrome (TS),
      causing half of the threefold excess mortality. As osteoprotegerin (OPG) is a
      potential biomarker of cardiovascular disease, this cross-sectional and
      prospective study aimed at elucidating OPG levels in TS and its relationship to
      aortic diameter as well as validated cardiovascular risk markers. METHODS: Adult
      women with TS (n = 99) were examined thrice (mean follow-up 4.7 +/- 0.5 years),
      and 68 age-matched healthy female controls were examined once. Aortic diameter
      was assessed by cardiovascular magnetic resonance. Twenty-four-hours blood
      pressure monitoring and biochemical assessments were also performed. RESULTS:
      Osteoprotegerin levels (median with range) were lower in TS (777 [326-10 569]
      ng/l) compared with controls (979 [398-1987] ng/l; P < 0.05) and did not change
      during follow-up. The OPG concentration was higher among women with TS older than
      50 years of age (996 [542-4996] vs 756 [326-10 569] ng/l; P < 0.05) with a trend
      towards a higher OPG in TS who were on antihypertensive medication (938 [490
      2638] vs 752 [326-10 569] ng/l; P = 0.09). Contrary to controls, OPG levels
      correlated with BSA-indexed aortic diameter (r = 0.31-0.45; P < 0.05), age (r =
      0.29; P < 0.05) and high-sensitivity C-reactive protein (r = 0.23; P = 0.02) and
      inversely with BSA (r = -0.20; P < 0.05), weight (r = -0.23; P < 0.05) and plasma
      oestradiol levels (r = -0.34; P < 0.05). CONCLUSION: Levels of OPG are lower in
      TS and correlate with aortic diameter, age, BSA, weight and oestradiol in TS, but
      not controls. Future studies are needed to assess whether OPG may serve as a
      biomarker of aortic or cardiovascular disease in TS.

PMID- 24923357
TI  - The ARID-HMG DNA-binding protein AtHMGB15 is required for pollen tube growth in
      Arabidopsis thaliana.
AB  - In flowering plants, male gametes (sperm cells) develop within male gametophytes
      (pollen grains) and are delivered to female gametes for double fertilization by
      pollen tubes. Therefore, pollen tube growth is crucial for reproduction. The
      mechanisms that control pollen tube growth remain poorly understood. In this
      study, we demonstrated that the ARID-HMG DNA-binding protein AtHMGB15 plays an
      important role in pollen tube growth. This protein is preferentially expressed in
      pollen grains and pollen tubes and is localized in the vegetative nuclei of the
      tricellular pollen grains and pollen tubes. Knocking down AtHMGB15 expression via
      a Ds insertion caused retarded pollen tube growth, leading to a significant
      reduction in the seed set. The athmgb15-1 mutation affected the expression of
      1686 genes in mature pollen, including those involved in cell wall formation and
      modification, cell signaling and cellular transport during pollen tube growth. In
      addition, it was observed that AtHMGB15 binds to DNA in vitro and interacts with
      the transcription factors AGL66 and AGL104, which are required for pollen
      maturation and pollen tube growth. These results suggest that AtHMGB15 functions
      in pollen tube growth through the regulation of gene expression. 

PMID- 24923358
TI  - Propulsion on a superhydrophobic ratchet.
AB  - Liquids in the Leidenfrost state were shown by Linke to self-propel if placed on
      ratchets. The vapour flow below the liquid rectified by the asymmetric teeth
      entrains levitating drops by viscosity. This effect is observed above the
      Leidenfrost temperature of the substrate, typically 200 degrees C for water. Here
      we show that coating ratchets with super-hydrophobic microtextures extends quick
      self-propulsion down to a substrate temperature of 100 degrees C, which exploits
      the persistence of Leidenfrost state with such coatings. Surprisingly, propulsion
      is even observed below 100 degrees C, implying that levitation is not necessary
      to induce the motion. Finally, we model the drop velocity in this novel "cold
      regime" of self-propulsion. 

PMID- 24923359
TI  - Regulatory volume increase and regulatory volume decrease responses in HL-1
      atrial myocytes.
AB  - BACKGROUND/AIMS: we have investigated whether cultured cardiomyocytes of the cell
      line HL-1 have the ability to perform regulatory volume responses both in
      hypotonic and hypertonic conditions. Furthermore, we characterized those
      regulatory responses and studied the effects of bumetanide and DIDS in volume
      regulation of HL-1 cells. METHODS: we used a light scattering system to measure
      the transient volume changes of HL-1 cells when subjected to osmotic challenge.
      RESULTS: We found that HL-1 cells correct for their volume excess by undergoing
      regulatory volume decrease (RVD), and also respond to hypertonic stress with a
      regulatory volume increase (RVI). Rate of RVD was 0.08 +/- 0.04 intensity/min,
      and rate of RVI was 0.09 +/- 0.01 intensity/min. Volume recovery was 83.68 +/-
      5.73 % for RVD and 92.3 +/- 2.3 % for RVI. Bumetanide 50 uM inhibited volume
      recovery, from 92.3 +/- 2.3 % (control) to 24.6 +/- 8.8 % and reduced the rate of
      RVI from 0.070 +/- 0.020 intensity/min (control) to 0.010 +/- 0.005
      intensity/min. 50 uM DIDS reduced volume recovery to 42.93 +/- 7.7 % and rate of
      RVI, to 0.03 +/- 0.01 intensity/min. CONCLUSIONS: these results suggest that
      bumetanide- and DIDS-sensitive mechanisms are involved in the RVI of HL-1 cells,
      which points to the involvement of the Na(+)/K(+)/2Cl(-) cotransporter and Cl(
      )/bicarbonate exchanger in RVI, respectively.

PMID- 24923360
TI  - Hologram quantitative structure activity relationship, docking, and molecular
      dynamics studies of inhibitors for CXCR4.
AB  - CXCR4 plays a crucial role as a co-receptor with CCR5 for HIV-1 anchoring to
      mammalian cell membrane and is implicated in cancer metastasis and inflammation.
      In the current work, we study the relationship of structure and activity of
      AMD11070 derivatives and other inhibitors of CXCR4 using HQSAR, docking and
      molecular dynamics (MD) simulations. We obtain an HQSAR model (q(2) = 0.779), and
      the HQSAR result illustrates that AMD11070 shows a high antiretroviral activity.
      As HQSAR only provides 2D information, we perform docking and MD to study the
      interaction of It1t, AMD3100, and AMD3465 with CXCR4. Our results illustrate that
      the binding are affected by two crucial residues Asp97 and Glu288. The butyl
      amine moiety of AMD11070 contributes to its high antiretroviral activity. Without
      a butyl amine moiety, (2,7a-Dihydro-1H-benzoimidazol-2-ylmethyl)-methyl-(5,6,7,8
      tetrahydro-quinolin-8-yl)-amine (compound 5a) shows low antiretroviral activity.
      Our results provide structural details about the interactions between the
      inhibitors and CXCR4, which are useful for rational drug design of CXCR4.

PMID- 24923361
TI  - Comparative chromosome painting of pronghorn (Antilocapra americana) and saola
      (Pseudoryx nghetinhensis) karyotypes with human and dromedary camel probes.
AB  - BACKGROUND: Pronghorn (Antilocapridae, 2n = 58) and saola (Bovidae, 2n = 50) are
      members of Pecora, a highly diversified group of even-toed hoofed mammals.
      Karyotypes of these species were not involved in chromosome painting studies
      despite their intriguing phylogenetic positions in Pecora. RESULTS: To trace the
      chromosome evolution during very fast radiation of main families from the common
      Pecoran ancestor, high-resolution comparative chromosome maps of pronghorn and
      saola with human (HSA) and dromedary camel (CDR) painting probes were
      established. The human and dromedary camel painting probes revealed 50 and 64
      conserved segments respectively in the pronghorn genome, while 51 and 63
      conserved segments respectively in the saola genome. Integrative analysis with
      published comparative maps showed that inversions in chromosomes homologous to
      CDR19/35/19 (HSA 10/20/10), CDR12/34/12 (HSA12/22/12/22), CDR10/33/10 (HSA 11)
      are present in representatives of all five living Pecoran families. The pronghorn
      karyotype could have formed from a putative 2n = 58 Pecoran ancestral karyotype
      by one fission and one fusion and that the saola karyotype differs from the
      presumed 2n = 60 bovid ancestral karyotype (2n = 60) by five fusions. CONCLUSION:
      The establishment of high-resolution comparative maps for pronghorn and saola has
      shed some new insights into the putative ancestral karyotype, chromosomal
      evolution and phylogenic relationships in Pecora. No cytogenetic signature
      rearrangements were found that could unite the Antilocapridae with Giraffidae or
      with any other Pecoran families. Our data on the saola support a separate
      position of Pseudorigyna subtribe rather than its affinity to either Bovina or
      Bubalina, but the saola phylogenetic position within Bovidae remains unresolved.

PMID- 24923362
TI  - Oral health conditions and cognitive functioning in middle and later adulthood.
AB  - BACKGROUND: The purpose of the present study was to examine the impact of oral
      health conditions on cognitive functioning on basis of data samples from several
      European countries. METHODS: Secondary analyses were conducted of data from wave
      2 of the Survey of Health, Ageing, and Retirement in Europe (SHARE) which
      includes 14 European countries and is intended to be representative of each
      country's middle and later adulthood population. Information on word recall,
      verbal fluency, and numeracy as well as information on chewing ability and
      denture wearing status was available for a total of 28,693 persons aged 50+.
      Multivariate regression analysis was used to detect influences of oral health
      parameters on cognitive functioning (p < 0.05). RESULTS: Persons with good
      chewing ability or without dentures had significantly better word recall, verbal
      fluency, and numeracy skills than persons with chewing impairment or with
      dentures. The observed patterns of parameter estimates imply differential oral
      health impacts on numeracy compared to word recall and verbal fluency.
      CONCLUSIONS: The present study provides novel large-scale epidemiological
      evidence supportive of an association between oral health and cognitive
      functioning. Future research should intend to verify the precise causal links
      between oral health conditions, various cognitive dimensions, and their neural
      correlates.

PMID- 24923363
TI  - Hepatocellular carcinoma based on cryptogenic liver disease: The most common non
      viral hepatocellular carcinoma in patients aged over 80 years.
AB  - AIM: To clarify the clinical features of patients with hepatocellular carcinoma
      (HCC) with cryptogenic liver diseases, we analyzed the data from a nationwide
      survey in Japan. METHODS: The survey was conducted in 2009. The factors examined
      included age and underlying liver diseases: alcoholic liver disease (ALD; n =
      991), non-alcoholic fatty liver disease (n = 292), modest alcohol intake (intake
      between 20 and 70 g/day, n = 214) and cryptogenic liver diseases (n = 316). We
      compared the clinical features of cryptogenic HCC among patient-age subgroups.
      RESULTS: HCC with ALD etiology was most common among the non-viral HCC patients
      under 80 years old; for those aged 80 years or older, cryptogenic HCC was the
      most common etiology. Among the cryptogenic HCC patients, the body mass index
      values and the prevalences of liver cirrhosis (LC) and diabetes mellitus (DM)
      were significantly lower in the 80 years or older group versus the 50-79 years
      group. In the 80 years or older group, 28% of the patients developed HCC without
      cirrhosis, obesity and DM. CONCLUSION: In the HCC patients aged 80 years and
      over, the etiology of most of the non-viral HCC cases was classified as
      cryptogenic. In light of our finding that the prevalences of obesity, DM and LC
      in the 80 years or older group of cryptogenic HCC patients were significantly
      lower those in the younger patients, it is apparent that analyses of HCC cases
      must take age differences into account.

PMID- 24923366
TI  - Highly efficient inverted polymer solar cells based on a cross-linkable water
      /alcohol-soluble conjugated polymer interlayer.
AB  - A cross-linkable water/alcohol soluble conjugated polymer (WSCP) material
      poly[9,9-bis(6'-(N,N-diethylamino)propyl)-fluorene-alt-9,9-bis(3-ethyl(oxetane-3
      ethyloxy)-hexyl) fluorene] (PFN-OX) was designed. The cross-linkable nature of
      PFN-OX is good for fabricating inverted polymer solar cells (PSCs) with well
      defined interface and investigating the detailed working mechanism of high
      efficiency inverted PSCs based on poly[4,8-bis(2-ethylhexyloxyl)benzo[1,2-b:4,5
      b']dithio-phene-2,6-diyl-alt-ethylhexyl-3-fluorothithieno[3,4-b]thiophene-2
      carboxylate-4,6-diyl] (PTB7) and (6,6)-phenyl-C71-butyric acid methyl ester
      (PC71BM) blend active layer. The detailed working mechanism of WSCP materials in
      high-efficiency PSCs were studied and can be summarized into the following three
      effects: a) PFN-OX tunes cathode work function to enhance open-circuit voltage
      (Voc); b) PFN-OX dopes PC71BM at interface to facilitate electron extraction; and
      c) PFN-OX extracts electrons and blocks holes to enhance fill factor (FF). On the
      basis of this understanding, the hole-blocking function of the PFN-OX interlayer
      was further improved with addition of a ZnO layer between ITO and PFN-OX, which
      led to inverted PSCs with a power conversion efficiency of 9.28% and fill factor
      high up to 74.4%. 

PMID- 24923365
TI  - Micropush-out dentine bond strength of a new gutta-percha and niobium phosphate
      glass composite.
AB  - AIM: To characterize an experimental gutta-percha and niobium phosphate glass
      composite (GNB) applied with a thermoplastic technique to the root canals without
      sealer in a moist environment and to evaluate its micropush-out bond strength to
      root canal wall dentine. METHODOLOGY: The root canals of sixty human mandibular
      pre-molars were prepared using rotary NiTi instruments and irrigation with sodium
      hypochlorite and EDTA. The teeth were then randomly divided into three groups
      according to the root filling material used: AH plus sealer and gutta-percha
      (AH), EndoSequence BC gutta-percha without sealer (GBC), and GNB without sealer.
      The root canals were filled with a single cone using warm vertical condensation.
      Push-out bond strengths associated with the filling materials in slices from
      middle root thirds was determined 30 days after root filling. The failure mode
      was analyzed with SEM. Analysis using EDX and SEM-EDS was carried out to verify
      the composition and distribution of the particles of the tested materials. Data
      were statistically analyzed by one-way anova and Tukey's test (P < 0.05).
      RESULTS: AH and GNB groups had bond strengths of 2.83 +/- 0.64 MPa and 2.68 +/-
      0.84 MPa, respectively, with no significant difference between them (P > 0.05).
      The GBC group had the lowest mean bond strength (1.34 +/- 0.42 MPa), which was
      significantly different compared with the other groups (P < 0.05). Cohesive
      failures prevailed in the AH group, whereas failures were mixed in the GBC and
      GNB groups. The SEM-EDS analysis on the surface and in the bulk of GBC revealed
      only a superficial coating of bioceramic particles. Glass particles were detected
      both on the surface and in the bulk of GNB. CONCLUSIONS: The experimental root
      filling composite (GNB) had an ability to adhere to root canal wall dentine equal
      to the current gold standard root filling with gutta-percha and sealer (AH Plus).

PMID- 24923367
TI  - Classical biological control of an invasive forest pest: a world perspective of
      the management of Sirex noctilio using the parasitoid Ibalia leucospoides
      (Hymenoptera: Ibaliidae).
AB  - Classical biological control is a key method for managing populations of pests in
      long-lived crops such as plantation forestry. The execution of biological control
      programmes in general, as the evaluation of potential natural enemies remains, to
      a large extent, an empirical endeavour. Thus, characterizing specific cases to
      determine patterns that may lead to more accurate predictions of success is an
      important goal of the much applied ecological research. We review the history of
      introduction, ecology and behaviour of the parasitoid Ibalia leucospoides. The
      species is a natural enemy of Sirex noctilio, one of the most important pests of
      pine afforestation worldwide. We use an invasion ecology perspective given the
      analogy between the main stages involved in classical biological control and the
      biological invasion processes. We conclude that success in the establishment, a
      common reason of failure in biocontrol, is not a limiting factor of success by I.
      leucospoides. A mismatch between the spread capacity of the parasitoid and that
      of its host could nevertheless affect control at a regional scale. In addition,
      we suggest that given its known life history traits, this natural enemy may be a
      better regulator than suppressor of the host population. Moreover, spatial and
      temporal refuges of the host population that may favour the local persistence of
      the interaction probably reduce the degree to which S. noctilio population is
      suppressed by the parasitoid. We emphasize the fact that some of the biological
      attributes that promote establishment may negatively affect suppression levels
      achieved. Studies on established non-native pest-parasitoid interactions may
      contribute to defining selection criteria for classical biological control which
      may prove especially useful in integrated pest management IPM programmes of
      invasive forest insects. 

PMID- 24923364
TI  - The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion
      injury and cardioprotection by preconditioning, postconditioning and remote
      conditioning.
AB  - Ischaemic heart disease is one of the leading causes of morbidity and mortality
      worldwide. The development of cardioprotective therapeutic agents remains a
      partly unmet need and a challenge for both medicine and industry, with
      significant financial and social implications. Protection of the myocardium can
      be achieved by mechanical vascular occlusions such as preconditioning (PC), when
      brief episodes of ischaemia/reperfusion (I/R) are experienced prior to ischaemia;
      postconditioning (PostC), when the brief episodes are experienced at the
      immediate onset of reperfusion; and remote conditioning (RC), when the brief
      episodes are experienced in another vascular territory. The elucidation of the
      signalling pathways, which underlie the protective effects of PC, PostC and RC,
      would be expected to reveal novel molecular targets for cardioprotection that
      could be modulated by pharmacological agents to prevent reperfusion injury.
      Gasotransmitters including NO, hydrogen sulphide (H2S) and carbon monoxide (CO)
      are a growing family of regulatory molecules that affect physiological and
      pathological functions. NO, H2S and CO share several common properties; they are
      beneficial at low concentrations but hazardous in higher amounts; they relax
      smooth muscle cells, inhibit apoptosis and exert anti-inflammatory effects. In
      the cardiovascular system, NO, H2S and CO induce vasorelaxation and promote
      cardioprotection. In this review article, we summarize current knowledge on the
      role of the gasotransmitters NO, H2S and CO in myocardial I/R injury and
      cardioprotection provided by conditioning strategies and highlight future
      perspectives in cardioprotection by NO, H2S, CO, as well as their donor
      molecules.

PMID- 24923368
TI  - Condom use among people living with HIV/AIDS attending Abejukolo General Hospital
      in Kogi State, North Central Nigeria.
AB  - BACKGROUND: Condom programming is an integral component in a range of HIV/AIDS
      prevention strategies and with repeated sexual contact among HIV-discordant
      couples, 98-100% of those who used latex condoms correctly and consistently did
      not become infected. The objective of this study is to determine condom use among
      people living with HIV/AIDS (PLWHA). METHODS: This is a cross-sectional survey
      carried out among 231 PLWHA and receiving care and treatment at General Hospital
      Abejukolo in Kogi State, Nigeria. The research instrument was interviewer
      administered questionnaire. The data obtained were analysed using EPI-INFO
      version 3.4.1 software and P-value of < 0.05 was significant for the study.
      RESULTS: About three-quarters (70.6%) of the respondents had ever used condom.
      Reasons given by respondents who did not use condom were: Desire for children
      (39.7%), and reduction of sexual pleasure (17.7%) and partner preference. More
      than half (56.0%) of the respondents with multiple partners did not use condom.
      About half 119 (51.5%) have used condom in the last sexual encounter. Gender,
      literacy level and disclosure of HIV status to partners significantly influence
      condom use during sexual intercourse. CONCLUSION: The poor uptake of condom among
      PLWHA underscores the need for government and other stakeholders in the
      management of HIV/AIDS to provide more enlightenment opportunities to address the
      gaps in condom use and disclosure of HIV status to partners.

PMID- 24923369
TI  - Progress toward elimination of malaria in Nigeria: uptake of artemisinin-based
      combination therapies for the treatment of malaria in households in Benin City.
AB  - BACKGROUND: The Roll Back Malaria (RBM) Partnership converged in Abuja in 2000.
      In 2005, Nigeria adopted artemisinin-based combination therapies (ACTs) as first
      line therapy for uncomplicated malaria. It was determined that by 2010, 80% of
      persons with malaria would be effectively treated. OBJECTIVES: To describe
      household practices for malaria treatment in Benin City; to explore demographic
      characteristics that may influence use of ACTs. MATERIALS AND METHODS: Multistage
      sampling technique was used to select households from each of the three local
      government areas in Benin City. Adult respondents were interviewed. Household
      reference persons (HRPs) were defined by International Labour Organization
      categories. Data were collected between December 2009 and February 2010 and were
      analyzed using Statistical Package for the Social Sciences Version 16.0, at a
      significance level of P < 0.05 (2-tailed). RESULTS: Of the 240 households
      selected, 217 were accessible, and respondents from 90% of these recalled the
      most recent episode (s) of malaria. One-third of malaria episodes had occurred in
      children younger than 5 years. ACTs were used in 4.9% of households; sulfadoxine
      pyrimethamine was the chief non-ACT antimalarial, followed by artemisinin
      monotherapies. Patent medicine stores were the most common sources of
      antimalarial medicines (38.2%), followed by private hospitals (20.3%) and private
      pharmacies (10.6%). Only 8.3% of households got their medicines from government
      hospitals. Having a HRP in managerial or professional categories was associated
      with a 6 times higher odds of using ACTs, compared to other occupational
      categories [odds ratio (OR) 5.8; confidence interval (CI) 1.470-20.758, P =
      0.016]. Fathers' tertiary or higher education was significantly associated with
      ACT use, but not mothers' (OR 0.054, CI 0.006-0.510; P = 0.011 and OR 0.905, CI
      0.195-4.198; P = 0.898, respectively). CONCLUSION: Ten years after the historic
      Abuja meeting, only 5% of households in Benin City used ACTs for the treatment of
      malaria, sourcing medicines chiefly from patent medicine stores and private
      hospitals. Fathers' level of education was significantly associated with ACT use.
      Interventions to eliminate malaria from Nigeria should mainstream the men folk
      and health care providers outside government hospitals, in line with the Nigerian
      reality.

PMID- 24923370
TI  - Substance dependence and mental health in northern Iran.
AB  - BACKGROUND: Today, substance dependence and illegal trading of narcotics is
      considered as a global issue. Since mental disorder has been reported in about
      90% of the substance dependents, this study aimed at determining the rate of
      mental health in the substance dependents in Sari Township in 2011. MATERIALS AND
      METHODS: In this study, 500 substance-dependent patients were selected using
      convenience sampling method. To collect data, SCL-90-R was used for the
      evaluation of their mental health and a demographic questionnaire was employed
      for identifying their personal information. The obtained data were analyzed by
      descriptive and inferential statistics using the SPSS software. RESULTS: It was
      found that 90.4% of the participants were susceptible to mental disorder. Most of
      them suffered from depression, psychoticism, interpersonal sensitivity, anxiety,
      and paranoia. Also, there was significant relationship between the mental health
      of single, divorced and married addicts (P < 0.21). CONCLUSION: Due to the
      presence of mental disorder in the substance-dependent patients, it is
      recommended to help treat them by providing them with education, psychotherapy,
      and psychiatric medication.

PMID- 24923371
TI  - Analysis of computed tomography features of fungal sinusitis and their
      correlation with nasal endoscopy and histopathology findings.
AB  - OBJECTIVE: The purpose of this study was to analyze the computed tomography (CT)
      features of fungal sinusitis and to correlate them with nasal endoscopy and
      histopathological findings. MATERIALS AND METHODS: Our study included 16 patients
      of either sex and any age group who presented in the otorhinolaryngology clinic
      at our hospital and had evidence of definite sinonasal disease on clinical
      evaluation. Multidetector CT was carried out on Somatom definition AS + 128 slice
      CT Machine by Siemens Germany Ltd. Axial sections were performed with the plane
      of data acquisition parallel to the hard palate and slice thickness of 3 mm,
      reconstructions at 0.75 mm in coronal and sagittal planes. Scanning parameters
      included 190 mA S, 120 KV and tube rotation time of 0.5 s. Provisional CT
      diagnosis was made in all cases and correlated with nasal endoscopy and
      histopathological findings. RESULTS: Out of total 16 patients, 12 showed
      immunocompromised status and had infection with mucormycosis. Out of 12, 9
      patients (75%) showed extension of disease beyond the sinonasal cavities and 4
      (33.3%) showed evidence of bone destruction. All patients with candidiasis showed
      soft-tissue attenuation with hyperdense areas on CT scan. Nearly, 66.6% patients
      with aspergillosis showed soft-tissue attenuation with hyperdense areas and
      expansion of sinonasal cavities. Fifteen patients (93%) were proved to be of
      fungal sinusitis on histopathology. One patient of non-specific granulomatous
      infection showed bone destruction and mimicked fungal sinusitis on CT.
      CONCLUSIONS: In the present study, fungal sinusitis could be correctly diagnosed
      on CT with high accuracy. Thus, understanding the different CT findings of fungal
      sinusitis allows the radiologist to play a crucial role in the diagnosis and
      prompt treatment.

PMID- 24923372
TI  - Agents for facilitation of laryngeal mask airway insertion: a comparative study
      between thiopentone sodium and propofol.
AB  - BACKGROUND: Development of endotracheal intubation to avoid deleterious effect on
      hemodynamic responses occurring during laryngoscopy and intubation compelled
      researchers to venture into alternative measures of airway management with subtle
      hemodynamic responses. This study was carried out to compare the conditions for
      laryngeal mask airways LMA insertion with widely used intravenous induction
      agents, thiopentone sodium and propofol, and also to compare the undesired
      responses occurring during LMA insertion with them. MATERIALS AND METHODS: The
      study was prospective, randomized, and double blind. All patients selected were
      randomly allocated into two groups: Group 1 (propofol) and group II
      (thiopentone). Preinduction heart rate and blood pressure were recorded. Sixty
      healthy adult patients of either sex belonging to age group of 20-60 years and
      ASA grade I or II, to undergo surgery less than 1 h, were selected for the study
      Patients were randomly allocated in two groups, 30 in each group. Premedication
      with midazolam 0.04 mg/kg and fentanyl 2 mg/kg done in both groups. Thereafter,
      group 1 was induced with 2 mg/kg of propofol and group 2 with 5 mg/kg of
      thiopentone sodium. RESULTS: The study revealed that, ease of insertion of LMA,
      was statistically significantly greater in group 1 when compared with group 2 (P
      0.05). The time required for successful insertion of LMA was lesser in group 1
      patients (53.8 +/- 7.77 s) than in group 2 patients (84.7 +/- 16.54 s) (P 0.001).
      CONCLUSION: Severity of undesired responses were more in group 2, as incremental
      boluses of respective induction agents were required in 20% patients in
      thiopentone group compared to only 6% patients in propofol group and 13% of
      patients in thiopentone group required rescue succinylcholine.

PMID- 24923373
TI  - Pattern and outcome of surgical management of nasolachrymal duct obstruction in
      children: a five year review.
AB  - OBJECTIVE: To determine the pattern of naso-lachrymal duct obstruction (NLDO) and
      outcome of dacryocystorhinostomy (DCR) in children in Aminu Kano Teaching
      Hospital Kano, over a 5-year period. PATIENTS AND METHODS: The clinic and theater
      registers were used to retrieve the records of all patients below the age of 15
      years who presented with NLDO. The information obtained included age, sex,
      duration, and types of clinical signs at presentation cause of obstruction and
      outcome of DCR. Successful outcome is defined as patent naso-lachrymal duct 1
      year after surgery. All the patients had external DCR with stent inserted into
      the lachrymal sac and anchored to the columella and left in situ for 6 weeks.
      Fortnightly for three visits then at 2 months intervals. At each visit, the
      patient had lachrymal punctal cannulation and irrigation with normal saline to
      ensure free drainage. RESULTS: There were 17 patients, 9 males and 8 females (M:
      F = 1.1: 1). Two patients (11.8%) had bilateral disease and 15 (88.2%) were
      unilateral. The patients' ages ranged between 2 and 10 years. The commonest
      presenting features were tearing and discharge. In 14 patients (82%) tearing
      started from birth though patients presented much later. Congenital NLDO occurred
      in 82%, and in the remaining 18%, obstruction was caused by depressed nasal
      fracture. Fifteen patients (88%) had successful outcome of DCR at 1-year follow
      up. The commonest complication noted was stent extrusion before 6 weeks in 17.6%
      of cases. Conclusion : NLDO was mostly of congenital origin and was characterized
      by delayed presentation. Patients have good outcome with external DCR.

PMID- 24923374
TI  - Macular volume and central foveal thickness measurements in normal eyes of
      healthy Nigerian adults using optical coherence tomography.
AB  - OBJECTIVE: To determine macular volume and central foveal thickness measurements
      in normal eyes of healthy Nigerian adults using Stratus optical coherence
      tomography. SUBJECTS AND METHODS: Consenting 100 adults Nigerians with normal
      eyes were recruited and examined using Carl Zeiss Stratus Optical Coherence
      Tomographer (OCT) machine Model 3000 software version 4.0. A fast macular
      thickness map scan protocol was employed. Central fovea is defined as locus of
      intersection of the radial scans. A default setting of six lines at 6 mm was
      used. Data was analyzed using the paired t-test for independence and linear
      regression. RESULTS: There were 200 eyes of 100 subjects with mean age of 36.4 +
      11.7 years (M: F = 3.3:1). The mean macula volume was 6.79 + 0.392 MUm 3 . It was
      6.861 +/- 0.297 in males, 6.496 +/- 0.520 in females and was statistically higher
      in males than females (P = 0.000). The mean central foveal thickness (MCFT) was
      149.58 +/- 32.470 MUm. It was 154.49 +/- 34.652 MUm in males and 133.33 +/-
      15.315 MUm in females. MCFT was significantly higher in males than females (P =
      0.000). CONCLUSION: Normal macular volume and central foveal thickness
      measurements in Nigerian adults is presented and is comparable to that of Indian
      and Chinese populations, but lower than reported in Caucasians.

PMID- 24923375
TI  - Posterior reversible encephalopathy syndrome in a adult female.
AB  - Posterior reversible encephalopathy syndrome is a clinico-neuroradiologic
      diagnosis, with rapidly evolving neurologic condition, characterized by headache,
      confusion, altered mental status, seizures, cortical blindness, lethargy, stupor,
      and occasionally, focal neurological signs accompanied by a typical computed
      tomography or magnetic resonance imaging pattern. With early recognition and
      treatment, complete resolution of symptoms occurs. Typical imaging findings
      characteristically involve the white matter bilaterally in the parieto-occipital
      regions. Atypical imaging finding of contrast enhancement of lesion can occur,
      but is less common. A 20-year-old primiparous lady presented with posterior
      reversible encephalopathy syndrome. To the best of our knowledge, this is the
      first documented case in Nigeria. This case-report highlights the importance of
      recognizing the salient imaging features in this lethal but reversible entity
      with prompt management. 

PMID- 24923376
TI  - Dyslipidemia among HIV-infected patients.

PMID- 24923377
TI  - Translation from research to clinical practice: fostering improved patient care
      through microscopicobservation drug susceptibility for tuberculosis diagnosis in
      Nigeria.

PMID- 24923378
TI  - Design and development of an in vitro tear replenishment system.
AB  - Understanding the cellular and molecular mechanisms of the corneal tissue and
      translating them into effective therapies requires organotypic culture systems
      that can better model the physiological conditions of the front of the eye. Human
      corneal in vitro models currently exist, however, the lack of tear replenishment
      limits corneal in vitro models' ability to accurately simulate the physiological
      environment of the human cornea. The tear replenishment system (TRS), a micro
      fluidic device, was developed to mimic the in vivo tear replenishment in the
      human eye in an in vitro corneal model. The TRS is capable of generating
      adjustable intermittent flow from 0.1 uL in every cycle. The TRS is a
      sterilizable device that is designed to fit standard 6-well cell culture plates.
      Experiments with the corneal models demonstrated that exposure to the TRS did not
      damage the integrity of the stratified cell culture. Contact lenses "worn" by the
      in vitro corneal model also remained moist at all times and the cytotoxicity of
      BAK could also be verified using this model. These in vitro results confirmed
      that the TRS presents novel avenues to assess lens-solution biocompatibility and
      drug delivery systems in a physiologically relevant milieu. 

PMID- 24923380
TI  - Introduction to the special issue on tissue engineering and regenerative
      medicine.

PMID- 24923381
TI  - An anatomical study of the lumbar external foraminal ligaments: appearance at MR
      imaging.
AB  - PURPOSE: The purpose of this study was to examine the MRI appearance of the
      ligaments within the external space of the lumbar intervertebral foramen by
      correlating MR images with the corresponding anatomic dissection of the cadaver
      lumbar spine. METHODS: This was a two part study. Part I of the anatomic study
      consisted of the dissection of lumbar specimens from one embalmed adult male
      cadaver. At each lumbar level the external ligamentous structures were identified
      and their origin, insertion and position were determined. Part II of the study
      consisted of the anatomical analysis of the external transforaminal ligaments in
      the 180 lumbar intervertebral foramina on the MR images (1.5 T) in the sagittal
      plane. The diagnostic procedure was performed on 18 individuals from 18 to 25
      years of age. RESULTS: The external transforaminal ligaments were observed at all
      levels and from both sides in the lumbar intervertebral foramen. The presence of
      the superior corporotransverse ligament was found in 45.56% intervertebral
      foramina, while the inferior corporotransverse ligament was found in 61.67%
      intervertebral foramina in the MRI. CONCLUSION: Our results confirm that external
      transforaminal ligaments are common structures in the intervertebral foramen. The
      results of this study show that the external transforaminal ligaments can be
      clearly visualized in MR images. It is crucial to have previous knowledge of the
      cadaveric specimens to recognize the transforaminal ligaments in MR images. The
      presence of these ligaments is clinically important because the ligaments could
      be the cause of nerve root compression or the low back pain syndrome.

PMID- 24923382
TI  - Large-scale complementary macroelectronics using hybrid integration of carbon
      nanotubes and IGZO thin-film transistors.
AB  - Carbon nanotubes and metal oxide semiconductors have emerged as important
      materials for p-type and n-type thin-film transistors, respectively; however,
      realizing sophisticated macroelectronics operating in complementary mode has been
      challenging due to the difficulty in making n-type carbon nanotube transistors
      and p-type metal oxide transistors. Here we report a hybrid integration of p-type
      carbon nanotube and n-type indium-gallium-zinc-oxide thin-film transistors to
      achieve large-scale (>1,000 transistors for 501-stage ring oscillators)
      complementary macroelectronic circuits on both rigid and flexible substrates.
      This approach of hybrid integration allows us to combine the strength of p-type
      carbon nanotube and n-type indium-gallium-zinc-oxide thin-film transistors, and
      offers high device yield and low device variation. Based on this approach, we
      report the successful demonstration of various logic gates (inverter, NAND and
      NOR gates), ring oscillators (from 51 stages to 501 stages) and dynamic logic
      circuits (dynamic inverter, NAND and NOR gates). 

PMID- 24923383
TI  - The effect of regular exercise on antioxidant enzyme activities and lipid
      peroxidation levels in both hippocampi after occluding one carotid in rat.
AB  - Regular exercise has beneficial effects on cerebrovascular diseases; however, its
      biochemical mechanisms are not fully known. The purpose of this study was to
      determine antioxidant enzyme activities and lipid peroxidation of both hippocampi
      after applying exercise followed by occluding one common carotid. Wistar rats
      were divided into four groups of control, exercise, hypoperfusion and exercise
      hypoperfusion (exe-hypo). In the exercise and exe-hypo groups, the rats were
      forced to run on a treadmill for 1 h a day for 2 months. The right common carotid
      of the animals in the (exe-hypo) group was occluded after the cessation of
      exercise. Surgery without occlusion of the carotid was applied on the control
      (without exercise) and exercise groups. All animals were sacrificed 1 and 24 h
      after surgery. The levels of malondialdehyde (MDA) and antioxidant enzyme
      activities in the hippocampi were measured. A significant interaction was
      observed between the exercise and hypoperfusion in both hippocampi (p<0.05). In
      comparison with the control group, there was significant elevation of catalase
      activity in the right and left hippocampus of the hypo group at 24 h (p<0.0001).
      Regarding the differences between the hemispheres, there was a significant
      increase in MDA and decrease in catalase activity in the left hippocampus in
      hypoperfusion group, but the exercise in the exe-hypo group succeeded in
      abolishing these alterations which were caused by hypoperfusion, This study shows
      that exercise pre-conditioning prevents some alterations in brain oxidant
      antioxidant status which are induced by cerebral hypoperfusion. Further studies
      are needed in order to clarify the mechanism of exercise.

PMID- 24923384
TI  - Determinants of torsades de pointes in older patients with drug-associated long
      QT syndrome: a case-control study.
AB  - OBJECTIVE: Many elderly patients are routinely exposed to drugs that may prolong
      the cardiac QT interval and cause Torsades de pointes (TdP). However, predictors
      of TdP in patients with drug-associated long QT syndrome (LQTS) are not fully
      understood, especially in the geriatric population. The objective of this study
      was to identify risk factors of TdP in elderly patients with drug-associated
      LQTS. METHODS: In this retrospective, case-control study, documented reports of
      drug-associated LQTS plus TdP (n = 125) and LQTS without TdP (n = 81) in patients
      >=65 years of age were retrieved from the French Pharmacovigilance Database over
      a 10-year period. Available clinical, biological, and drug therapy data were
      compared in the two groups and logistic regression was performed to identify
      significant predictors of TdP. RESULTS: The uncorrected QT interval was
      significantly longer in patients with TdP than in patients without TdP (577 +/-
      79 vs. 519 +/- 68 ms; p = 0.0001). The number of drugs with a known risk of TdP
      administered to each patient was not a predictor of arrhythmia, nor was female
      gender. Logistic regression analysis identified the uncorrected QT interval as
      the only significant predictor of TdP. The receiver operating characteristic
      curve analysis was characterized by an area under the curve of 0.77 (95 %
      confidence interval 0.64-0.88) and a QT cutoff of 550 ms. CONCLUSION: The
      uncorrected QT interval was significantly associated with the probability of TdP
      in elderly patients with acquired, drug-associated LQTS.

PMID- 24923385
TI  - A meta-synthesis of potentially inappropriate prescribing in older patients.
AB  - BACKGROUND: Potentially inappropriate prescribing (PIP) is commonly seen amongst
      the older population in all clinical settings, as indicated by several prevalence
      studies in several countries. Quantitative work such as this confirms that this
      is a global public health problem likely to grow in tandem with ageing of the
      global population. However, less attention has been focused on why it is
      happening and how it can be prevented. OBJECTIVE: The objective of this paper is
      to synthesise qualitative studies that explore PIP in older patients, in an
      effort to understand why it happens from a prescriber's perspective and to
      generate a new theory to guide future interventional studies aimed at minimising
      it in older people. To date, there is no published systematic synthesis of this
      type. METHODS: Papers were deemed suitable for inclusion if they used qualitative
      methods, explored some area of PIP in patients over 65 years of age, were
      published in English and had available published abstracts. Four databases were
      systematically searched for papers published up to the end of April 2013: PubMed,
      Embase, CINAHL and Web of Knowledge. No date restrictions were applied. Key words
      searched were: Qualitative AND (Inappropriate* OR Appropriate* OR Safe) AND
      (Elderly OR Aged OR Geriatric* OR Old*) AND Prescri*. Reference lists were then
      searched for other suitable papers. Critical Appraisal Skills Programme criteria
      were used to assess quality. Meta-ethnography was used to synthesise the papers.
      RESULTS: Out of 624 papers identified, seven papers were deemed relevant. Four
      key concepts were identified as being causal factors in PIP: (1) the need to
      please the patient, (2) feeling of being forced to prescribe, (3) tension between
      prescribing experience and prescribing guidelines and (4) prescriber fear. These
      were re-interpreted in a line of argument synthesis indicating that some doctors
      have self-perceived restrictions with regard to prescribing appropriately because
      of a combination of factors, rather than any one dominant factor. CONCLUSION:
      Prevention of PIP may be favourably influenced by addressing the key interactive
      determinants of inappropriate prescribing behaviour.

PMID- 24923386
TI  - Exercise mitigates the adverse effects of hyperhomocysteinemia on macrophages,
      MMP-9, skeletal muscle, and white adipocytes.
AB  - Regular exercise is a great medicine with its benefits encompassing everything
      from prevention of cardiovascular risk to alleviation of different muscular
      myopathies. Interestingly, elevated levels of homocysteine (Hcy), also known as
      hyperhomocysteinemia (HHcy), antagonizes beta-2 adrenergic receptors (beta2AR),
      gamma amino butyric acid (GABA), and peroxisome proliferator-activated receptor
      gamma (PPARgamma) receptors. HHcy also stimulates an elevation of the M1/M2
      macrophage ratio, resulting in a more inflammatory profile. In this review we
      discuss several potential targets altered by HHcy that result in myopathy and
      excessive fat accumulation. Several of these HHcy mediated changes can be
      countered by exercise and culminate into mitigation of HHcy induced myopathy and
      metabolic syndrome. We suggest that exercise directly impacts levels of Hcy,
      matrix metalloproteinase 9 (MMP-9), macrophages, and G-protein coupled receptors
      (GPCRs, especially Gs). While HHcy promotes the M1 macrophage phenotype, it
      appears that exercise may diminish the M1/M2 ratio, resulting in a less
      inflammatory phenotype. HHcy through its influence on GPCRs, specifically
      beta2AR, PPARgamma and GABA receptors, promotes accumulation of white fat,
      whereas exercise enhances the browning of white fat and counters HHcy-mediated
      effects on GPCRs. Alleviation of HHcy-associated pathologies with exercise also
      includes reversal of excessive MMP-9 activation. Moreover, exercise, by reducing
      plasma Hcy levels, may prevent skeletal muscle myopathy, improve exercise
      capacity and rescue the obese phenotype. The purpose of this review is to
      summarize the pathological conditions surrounding HHcy and to clarify the
      importance of regular exercise as a method of disease prevention.

PMID- 24923388
TI  - Cerebral concussion: a historical perspective.
AB  - No topic in sports has gathered more attention and publicity than the diagnosis,
      management, and long-term effects of cerebral concussion. The relevant history of
      concussion starts in 1905 when President Theodore Roosevelt drew attention to the
      football 'death harvest'. Soon after, rules started to change to reduce the
      amount and severity of head injuries in football. Up until 1980, the primary
      focus regarding concussions was to diagnose a potentially fatal intracranial
      hemorrhage. While aware of long-term consequences of concussions, the perception
      at the time was that virtually all concussions would 'clear' with time and rest.
      Concussion management guidelines gave way to objective neuropsychological testing
      in the early 1990s with the development of the ImPACTTM (Immediate Post
      Concussion Assessment and Cognitive Testing) neurocognitive test. Led by
      organized football, in 1994 the National Football League (NFL) formed the Mild
      Traumatic Brain Injury Committee which began to investigate the cause of
      concussions, evaluate equipment (particularly helmets), and recommend methods for
      prevention. In 2005, the first case of chronic traumatic encephalopathy was
      described in a deceased football player, raising concerns about the long-term
      consequences of head injuries and concussions. Major advancements in contact
      sports and the military are underway to reduce the incidence of concussions and
      subconcussive blows to the head.

PMID- 24923387
TI  - Expression analysis of mouse Rhobtb3 using a LacZ reporter and preliminary
      characterization of a knockout strain.
AB  - RhoBTB3 is an atypical member of the Rho family of small GTPases. It localizes at
      the Golgi apparatus and endosomes and is involved in vesicle trafficking and in
      targeting proteins for degradation in the proteasome. Previous studies using
      Northern blot analysis showed that Rhobtb3 is ubiquitously expressed in adult
      mice, but expression is particularly high in brain, heart and uterus. The gene is
      also expressed between embryonic days 11.5 and 17.5. To investigate the specific
      cell types that express this gene across tissues, both in the embryo and in the
      adult organism, we have made use of a gene trap mouse strain that expresses the
      LacZ gene under the transcriptional control of the endogenous Rhobtb3 promoter.
      Histochemical detection of beta-galactosidase expression revealed a profile
      characterized by nearly ubiquitous expression of Rhobtb3 in the embryo, but with
      particularly high levels in bone, cartilage, all types of muscle, testis and
      restricted areas of the nervous system. In the adult, expression persists at much
      lower levels in cardiac muscle, the tunica media of blood vessels and cartilage
      and at high levels in the seminiferous tubules. A general preliminary
      characterization of this gene trap mouse strain revealed reduced viability, a
      postnatal growth defect and reduced testis size. Our results should pave the way
      for future studies aimed at investigating the roles of RhoBTB3 in tissue
      development and in cardiac, vascular and testicular function. 

PMID- 24923389
TI  - Biomechanics of concussion.
AB  - This report provides an overview of the biomechanics associated with mild
      traumatic brain injury (TBI), also known as concussion. Specifically, the role of
      angular acceleration in modulating concussion onset and severity is highlighted.
      Studies conducted and published from the 1960s to the 1980s provided initial
      estimates for TBI tolerance due to high rate head rotation. However, injury
      levels in those studies were more severe than what is considered to be concussion
      in the contemporary environment. Therefore, this issue deserves additional
      attention to provide quantitative estimates for concussive tolerance due to head
      rotational acceleration focusing on the types of clinical outcomes described
      today. Likewise, concussion in military personnel has notably increased in
      current conflicts due to the incorporation of improvised explosive devices and
      roadside bombs. Clinical evidence indicates that outcomes from concussion due to
      blast may be quite different from those due to head rotational acceleration. This
      report also provides an overview of blast concussion mechanisms and highlights
      some of the recent preclinical work in this area. As with head rotational
      acceleration, blast tolerance is necessary to understand the scope of this
      problem, better protect these personnel, and provide more informed return-to-duty
      guidelines for service members.

PMID- 24923390
TI  - The neurophysiology of concussion.
AB  - The following report reviews our current understanding of the neurobiological
      response to concussion which is often referred to as mild traumatic brain injury.
      The historical accomplishments to reveal the brain's response to this injury are
      discussed along with the neurochemical and metabolic cascade that results in an
      energy crisis. The massive ionic flux induced by cerebral concussion is discussed
      as it pertains to primarily potassium and calcium. The ensuing metabolic demands
      placed on cells exposed to this ionic flux is discussed as it relates to an
      injury-induced diaschisis. As this cascade produces neuronal dysfunction and
      corresponding deficits, it also results in a state of vulnerability to secondary
      insults and long-term neurological problems. While experimental studies are the
      primary focus of this report, relevant human observations are discussed and put
      into context. It is now clear that cerebral concussion is not a benign event. It
      carries with it neuroscientific consequences that result in symptoms and an
      increase in risk for many other challenges to the central nervous system.

PMID- 24923391
TI  - Chronic traumatic encephalopathy.
AB  - Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative
      syndrome, which is caused by single, episodic, or repetitive blunt force impacts
      to the head and transfer of acceleration-deceleration forces to the brain. CTE
      presents clinically as a composite syndrome of mood disorders and behavioral and
      cognitive impairment, with or without sensorimotor impairment. Symptoms of CTE
      may begin with persistent symptoms of acute traumatic brain injury (TBI)
      following a documented episode of brain trauma or after a latent period that may
      range from days to weeks to months and years, up to 40 years following a
      documented episode of brain trauma or cessation of repetitive TBI. Posttraumatic
      encephalopathy is distinct from CTE, can be comorbid with CTE, and is a
      clinicopathologic syndrome induced by focal and/or diffuse, gross and/or
      microscopic destruction of brain tissue following brain trauma. The brain of a
      CTE sufferer may appear grossly unremarkable, but shows microscopic evidence of
      primary and secondary proteinopathies. The primary proteinopathy of CTE is
      tauopathy, while secondary proteinopathies may include, but are not limited to,
      amyloidopathy and TDP proteinopathy. Reported prevalence rates of CTE in cohorts
      exposed to TBI ranges from 3 to 80% across age groups.

PMID- 24923392
TI  - Cumulative effects of repetitive mild traumatic brain injury.
AB  - The majority of traumatic brain injuries (TBI) in the USA are mild in severity.
      Sports, particularly American football, and military experience are especially
      associated with repetitive, mild TBI (mTBI). The consequences of repetitive brain
      injury have garnered increasing scientific and public attention following reports
      of altered mood and behavior, as well as progressive neurological dysfunction
      many years after injury. This report provides an up-to-date review of the
      clinical, pathological, and pathophysiological changes associated with repetitive
      mTBI, and their potential for cumulative effects in certain individuals.

PMID- 24923393
TI  - Understanding concussive injuries using investigational imaging methods.
AB  - Concussions have long been understood to be an invisible injury. Indeed,
      conventional imaging techniques [computed tomography and magnetic resonance
      imaging (MRI)] are largely ineffective in elucidating concussive injuries. More
      advanced techniques are being used experimentally to help delineate the
      underlying pathophysiology of concussive injuries on metabolic as well as
      ultrastructural levels. The current report reviews the data from several of these
      techniques including functional MRI, single-photon emission computed tomography,
      positron emission tomography, diffusion tensor imaging, and magnetic resonance
      spectroscopy. Each technique is briefly described, followed by a summary of the
      findings specific to concussive injuries. Overall, there is mounting evidence to
      suggest that each technique has utility in describing and explaining postinjury
      changes in the brain. Overall, concussive injuries are evident using the various
      aforementioned neuroimaging modalities and suggest at a minimum the concussed
      brain is different in the acute and subacute postinjury phases with several other
      studies suggesting that changes are persistent well beyond, especially in those
      patients with persistent symptoms.

PMID- 24923394
TI  - Neurometabolic, electrophysiological, and imaging abnormalities.
AB  - Sport-related concussions affect millions of athletes every year, but they
      generally present no anatomic alterations when examined using conventional
      magnetic resonance imaging or a computed tomography scan. Because the damage
      occurring after a head injury seems to be more functional than structural, these
      techniques are unable to detect subtle alterations. The absence of detectable
      structural alterations using traditional neuroimaging methods, the presence of
      persistent symptoms in some athletes, and the risk of developing
      neurodegenerative diseases emphasize the importance of assessing the impacts of a
      head injury with alternative neuroimaging techniques. Electrophysiological
      methods, magnetic resonance spectroscopy, and diffusion tensor imaging are useful
      techniques that are sensitive to the effects of a brain trauma, which provide
      complementary information to allow a more complete understanding of the multiple
      pathophysiological processes involved in concussive events. This report
      summarizes recent data using neurophysiological and neuroimaging techniques to
      better understand the acute and chronic effects of sport-related concussions.

PMID- 24923395
TI  - Detection of white matter injury in concussion using high-definition fiber
      tractography.
AB  - Over the last few decades, structural imaging techniques of the human brain have
      undergone significant strides. High resolution provided by recent developments in
      magnetic resonance imaging (MRI) allows improved detection of injured regions in
      patients with moderate-to-severe traumatic brain injury (TBI). In addition,
      diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained
      much interest recently due to its possible utility in detecting structural
      integrity of white matter pathways in mild TBI (mTBI) cases. However, the results
      from recent DTI studies in mTBI patients remain equivocal. Also, there are
      important shortcomings for DTI such as limited resolution in areas of multiple
      crossings and false tract formation. The detection of white matter damage in
      concussion remains challenging, and development of imaging biomarkers for mTBI is
      still in great need. In this chapter, we discuss our experience with high
      definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique.
      We also discuss ongoing developments and specific advantages HDFT may offer
      concussion patients.

PMID- 24923396
TI  - Magnetoencephalography in the diagnosis of concussion.
AB  - Magnetoencephalography (MEG) is a biomedical technique which measures the
      magnetic fields emitted by the brain, generated by neuronal activity. Commercial
      whole-head MEG units have been available for about 15 years, but currently there
      are only about 20 such units operating in the USA. Here, we review the basic
      concepts of MEG and list some of the usual clinical indications: noninvasive
      localization of epileptic spikes and presurgical mapping of eloquent cortex. We
      then discuss using MEG to diagnose mild traumatic brain injury (mTBI;
      concussions). Injured brain tissues in TBI patients generate abnormal low
      frequency magnetic activity (delta-waves: 1-4 Hz) that can be measured and
      localized by MEG. These abnormal delta-waves originate from neurons that
      experience deafferentation from axonal injury to the associated white matter
      fiber tracts, also manifested on diffusion tensor imaging as reduced fractional
      anisotropy. Magnetoencephalographic evaluation of abnormal delta-waves (1-4 Hz)
      is probably the most sensitive objective test to diagnose concussions. An
      automated MEG low-frequency (slow wave) source imaging method, frequency-domain
      vector-based spatiotemporal analysis using a L1-minimum norm (VESTAL), achieved a
      positive finding rate of 87% for diagnosing concussions (blast-induced plus
      nonblast), 100% for moderate TBI, and no false-positive diagnoses in normal
      controls. There were also significant correlations between the number of cortical
      regions generating abnormal slow waves and the total postconcussive symptom
      scores in TBI patients.

PMID- 24923397
TI  - Evidence-based management of sport-related concussion.
AB  - Concussion is not only one of the most common injuries encountered by athletes
      participating in contact and collision sports, but also among the most complex
      injuries to manage in a sports medicine setting. Over the past two decades, we
      have made great progress in advancing the basic and clinical science of
      concussion. These advances have had enormous clinical translational value for
      developing evidence-based guidelines for management of concussion in sports.
      Applied clinical research has clarified the defining characteristics of sport
      related concussion (SRC) that support new diagnostic criteria. At the same time,
      major advancements have been realized in the development and validation of
      clinical tools that allow a more objective and accurate assessment of concussion
      and performance-based measures of recovery. These tools provide clinicians with a
      more informed basis for determining an athlete's cognitive and physical fitness
      to return to competition after concussion. Standardized injury management
      protocols that systematically prescribe rest, graded activity, and return to play
      have been adopted in nearly all clinical settings. Herein, we briefly summarize
      the findings and recommendations from several national and international
      consensus guidelines and position statements on best practice in the evaluation
      and management of SRC.

PMID- 24923398
TI  - In-office management of sport-related concussion.
AB  - The field of sport-related concussion has grown exponentially over the past
      decade, with more concussion-specific clinics being identified in major hospital
      systems as well as independent practitioner's offices. To date, there is no
      standardized in-office protocol for managing ongoing symptoms. The University of
      Pittsburgh Medical Center (UPMC) Sports Concussion Program, established in 2000,
      is one of the largest programs in the USA, pioneering the way in clinical
      management, research, and education of sport-related concussion. This report will
      outline the essential components of a successful concussion clinic, using the
      UPMC Sports Concussion Program as a case example of best practice. We will share
      several case studies illustrating the individualized and complex nature of this
      injury, as well as review important rehabilitation components.

PMID- 24923399
TI  - Treating prolonged symptoms of mild traumatic brain injury: neuropharmacology.
AB  - The clinical presentation of concussion can vary widely as patients experience
      any number of symptoms including headache, dizziness, cognitive symptoms of
      difficulty with concentration and memory, sleep dysregulation, and mood
      disturbances. The variability in clinical presentation underscores the importance
      of thorough history-taking to clearly understand the clinical picture and to
      allow individualization of the treatment plan. Most postconcussive symptoms are
      transient in nature and respond to conservative measures, including education of
      the patient and their caregivers. For those individuals whose symptoms persist or
      significantly impair quality of life, pharmacologic intervention may be
      warranted. Though few studies have investigated the use of pharmacology for
      treatment of postconcussion syndrome specifically, targeted treatment of
      medications known to improve selected symptoms can be considered.

PMID- 24923400
TI  - Rehabilitation from postconcussion syndrome: nonpharmacological treatment.
AB  - Following mild traumatic brain injury (mTBI), one or more symptoms commonly occur
      that are known as the postconcussion syndrome (PCS). While PCS typically resolves
      within a few weeks of injury for most concussed patients, some patients have a
      more prolonged or otherwise adverse recovery course. There is relatively little
      systematic research on the treatment of PCS. This report offers strategies for
      nonpharmacological treatment of PCS during the acute, subacute, and chronic
      stages of recovery following mTBI. The treatment strategies are supported by
      clinical consensus and the limited evidence-based research wherever possible.
      Core treatment strategies emphasize (1) education about mTBI, PCS, and the
      natural recovery course, (2) reassurance of a good outcome, (3) reduction in
      activity level and refrain from hazardous behaviors during the acute phase, (4)
      gradual return to lifestyle activities as symptoms permit, (5) careful monitoring
      and early intervention for adverse emotional responses, (6) symptom-specific
      treatment when needed, and (7) ready access to providers during acute and
      subacute recovery periods.

PMID- 24923401
TI  - Concussion in ice hockey.
AB  - Ice hockey is an aggressive and fast-paced sport which has a high risk of injury,
      concussions in particular. Although serious head injury has been recognized for
      nearly 50 years, an increase in mainstream media attention in recent years has
      led to unprecedented public awareness. As a result, the National Hockey League
      (NHL) and other professional leagues around the world have initiated concussion
      protocols in order to better prevent, recognize, and treat concussions. With over
      1,000,000 youth hockey participants in Canada and the USA combined, concussion is
      an issue that reaches beyond the professional level. In this report we review the
      incidence, evaluation, treatment, return-to-play protocol, and prevention efforts
      related to concussion in ice hockey.

PMID- 24923402
TI  - Management of concussion in the professional football player.
AB  - There is no other sport that has come under greater scrutiny surrounding the
      incidence and treatment of concussion than football, and there is no other
      professional sports league that has experienced more intense focus of its
      handling of concussions than the National Football League (NFL). The NFL has
      received significant criticism of their management of concussion in players from
      both the popular press and the medical community. However, those working with
      active NFL players have changed their assessment and treatment of these injuries
      as the knowledge of concussions has evolved over time. We review the current
      approach to the management of concussions in the professional football player.

PMID- 24923403
TI  - Developing an interdisciplinary community-based sports concussion management
      program.
AB  - The increasing incidence and associated consequences of sport-related concussion
      have been at the forefront of public health concerns in recent years, prompting
      the need for safe and effective management guidelines and availability of
      appropriately trained healthcare providers. In this report we provide practical
      and user-friendly information regarding several important factors to consider
      when developing a sports concussion program, including how to select relevant
      team members, assess community needs and available resources, provide concussion
      education, secure and nurture partnerships with athletic programs, implement
      management strategies that align with current practice standards, and cater to
      athletes' unique needs in terms of program accessibility. It is hoped that the
      knowledge shared and proposed recommendations will be beneficial for guiding both
      newly developing and established concussion programs alike.

PMID- 24923404
TI  - The multidisciplinary concussion management program.
AB  - Over the past decade, research has increased scientific and public knowledge
      about the importance of identification and proper management of concussion. These
      concerns have prompted many state, regional, and private organizations to mandate
      the creation of, and strict adherence to, concussion management protocols,
      particularly with regard to sport-related concussion and subsequent return to
      play. Because of the individualized nature of the concussive injury and its
      recovery, a multidisciplinary approach provides comprehensive patient care that
      best addresses treatment and management of changing symptoms and their impact on
      multiple aspects of a patient's life and overall function. The current report
      will explore a model of multidisciplinary concussion management from program
      establishment and baseline testing to recovery from chronic postconcussion
      symptoms.

PMID- 24923405
TI  - Vulnerability in speed of visuomotor ability.
AB  - The aim of this report is to illustrate the utility of neurocognitive testing as
      an investigative method to establish the presence of persistent effects of
      concussive brain injury amongst players of a contact sport with high risk of such
      injury. The report reviews the outcomes of three previously published
      neuropsychological studies on South African Rugby Union (hereafter 'rugby') from
      school through to the national adult level. The diagnostic utility of
      differential effects per se, as well as differential practice effects on
      visuomotor function, as a means of distinguishing poorer neurocognitive outcome
      for rugby versus demographically equivalent noncontact sports players, is
      described. From various methodological angles, at each level of play, the
      reviewed studies attest to the presence of long-term vulnerability in visuomotor
      speed in association with participation in rugby, in turn implicating diffuse
      frontotemporal dysfunction due to repetitive concussive and subconcussive injury
      amongst rugby players. As visuomotor speed is a prime function called upon for
      optimal scholastic and occupational performance, the robustly demonstrated
      decrement is of immediate clinical importance. Of critical heuristic relevance,
      however, is evidence of residual brain dysfunction in association with rugby as
      early as school level, which may ultimately be the precursor of chronic traumatic
      encephalopathy.

PMID- 24923406
TI  - Detecting eye movement abnormalities from concussion.
AB  - An attention-based biomarker may be useful for concussion screening. A key role
      of attention is to generate time-based expectancies of specific sensory
      information, and it is postulated that postconcussion cognitive impairments and
      symptoms may stem from a primary deficit in this predictive timing mechanism.
      There is a close relationship between gaze and attention, but in addressing
      predictive timing, there is a need for an appropriate testing paradigm and
      methods to quantify oculomotor anomalies. We have utilized a continuous
      predictive visual tracking paradigm because human visual tracking requires
      predicting the temporal course of a stimulus and dynamically synchronizing the
      required action with the stimulus. We have shown that concussion patients often
      show disrupted gaze-target synchronization characterized by large gaze position
      error variability and overall phase advancement. Various attention components
      interact with visual tracking, and thus there is a possibility that different
      neurological and physiological conditions produce identifiable visual tracking
      characteristics. Analyzing neuromotor functions, specifically oculomotor
      synchronization, can provide a fast, accurate, and reliable assessment of
      cognitive functions.

PMID- 24923407
TI  - Neurodegenerative changes after mild traumatic brain injury.
AB  - A link between mild traumatic brain injury (mTBI) and neurodegenerative diseases,
      specifically Alzheimer's disease and chronic traumatic encephalopathy (CTE), has
      long been suspected. Shared clinical symptomology - most notably the prominent
      role of central auditory dysfunction and sleep-wake disturbances in both disease
      states - and similar findings on postmortem pathological examination has further
      reinforced suspected commonality between these seemingly disparate entities.
      However, conventional imaging techniques, including computed tomography and
      anatomic magnetic resonance, are unable to detect the symptomatic injuries in
      mTBI patients and therefore detection of neurodegenerative changes in vivo has
      previously not been reported. Recent research using diffusion tensor imaging, a
      novel imaging technique, and focused on patient-reported symptoms has for the
      first time demonstrated imaging findings in mTBI patients in vivo that are
      strikingly similar to Alzheimer's dementia and CTE. Moving forward, research will
      focus on identifying what renders certain patients with mTBI susceptible to
      developing full-fledged Alzheimer's disease and CTE later in life.

PMID- 24923408
TI  - Future directions in brain injury research.
AB  - This paper reviews the potential future directions that are important for brain
      injury research, especially with regard to concussion. The avenues of proposed
      research are categorized according to current concepts of concussion, types of
      concussion, and a global schema for globally reducing the burden of concussion.

PMID- 24923410
TI  - A new mild synthetic route to N-arylated pyridazinones from aryldiazonium salts.
AB  - An efficient method for the synthesis of N-arylated pyridazinones from potassium
      2-furantrifluoroborate and aryldiazonium salts is described. The reaction was run
      in water at 0-5  degrees C in short reaction times and without any catalyst or
      additive. A mechanistic proposal is made based on the experimental data and DFT
      calculations. 

PMID- 24923411
TI  - Acid-sensing ion channel 3 decreases phosphorylation of extracellular signal
      regulated kinases and induces synoviocyte cell death by increasing intracellular
      calcium.
AB  - INTRODUCTION: Acid-sensing ion channel 3 (ASIC3) is expressed in synoviocytes,
      activated by decreases in pH, and reduces inflammation in animal models of
      inflammatory arthritis. The purpose of the current study was to characterize
      potential mechanisms underlying the control of inflammation by ASIC3 in
      fibroblast-like synoviocytes (FLS). METHODS: Experiments were performed in
      cultured FLS from wild-type (WT) and ASIC3-/- mice, ASIC1-/- mice, and people
      with rheumatoid arthritis. We assessed the effects of acidic pH with and without
      interleukin-1beta on FLS and the role of ASICs in modulating intracellular
      calcium [Ca(2+)](i), mitogen activated kinase (MAP kinase) expression, and cell
      death. [Ca(2+)](i) was assessed by fluorescent calcium imaging, MAP kinases were
      measured by Western Blots; ASIC, cytokine and protease mRNA expression were
      measured by quantitative PCR and cell death was measured with a LIVE/DEAD assay.
      RESULTS: Acidic pH increased [Ca(2+)](i) and decreased p-ERK expression in WT
      FLS; these effects were significantly smaller in ASIC3-/- FLS and were prevented
      by blockade of [Ca(2+)]i. Blockade of protein phosphatase 2A (PP2A) prevented the
      pH-induced decreases in p-ERK. In WT FLS, IL-1beta increases ASIC3 mRNA, and when
      combined with acidic pH enhances [Ca(2+)](i), p-ERK, IL-6 and metalloprotienase
      mRNA, and cell death. Inhibitors of [Ca(2+)](i) and ERK prevented cell death
      induced by pH 6.0 in combination with IL-1beta in WT FLS. CONCLUSIONS: Decreased
      pH activates ASIC3 resulting in increased [Ca(2+)](i), and decreased p-ERK. Under
      inflammatory conditions, acidic pH results in enhanced [Ca(2+)](i) and
      phosphorylation of extracellular signal-regulated kinase that leads to cell
      death. Thus, activation of ASIC3 on FLS by acidic pH from an inflamed joint could
      limit synovial proliferation resulting in reduced accumulation of inflammatory
      mediators and subsequent joint damage.

PMID- 24923412
TI  - Comparing gendered and generic representations of mental illness in Canadian
      newspapers: an exploration of the chivalry hypothesis.
AB  - PURPOSE: The 'chivalry hypothesis' posits that woman are treated more
      compassionately by the media when compared with men. To our knowledge, no
      research study has explored the chivalry hypothesis as applied to people with
      mental illness. As such, we set out to compare three types of newspaper articles,
      those that focus on (1) mental illness generically; (2) a woman with mental
      illness; and (3) a man with mental illness. METHODS: We conducted a content
      analysis of 1,168 newspaper articles relating to mental health over 6 months. We
      obtained articles through media retrieval software using various search terms. We
      read and coded articles for the presence or absence of themes and content.
      Frequency counts and proportions were generated for each theme, which were
      compared across the three types of articles using Chi-square tests. RESULTS:
      Generic articles were more positive than articles about individuals. They were
      significantly more likely to quote mental health experts, and have recovery,
      inadequate resources, and etiology as themes. Articles that depicted men were
      significantly more likely to have stigmatizing content and violence as themes.
      Articles depicting women were significantly more likely to quote mental health
      experts, discuss mental health interventions, and have recovery and inadequate
      resources as themes. CONCLUSION: The findings lend some support to the chivalry
      hypothesis, in as much as articles about women were significantly more positive.
      Articles about men were significantly more negative, though this may be partially
      accounted for by elevated rates of violent crime in men. Generic articles were
      the most extensively well informed.

PMID- 24923413
TI  - Empirical mode decomposition and neural network for the classification of
      electroretinographic data.
AB  - The processing of biosignals is increasingly being utilized in ambulatory
      situations in order to extract significant signals' features that can help in
      clinical diagnosis. However, this task is hampered by the fact that biomedical
      signals exhibit a complex behavior characterized by strong nonlinear and non
      stationary properties that cannot always be perceived by simple visual
      examination. New processing methods need be considered. In this context, we
      propose a signal processing method, based on empirical mode decomposition and
      artificial neural networks, to analyze electroretinograms, i.e., the retinal
      response to a light flash, with the aim to detect and classify retinal diseases.
      The present application focuses on two retinal pathologies: achromatopsia, which
      is a cone disease, and congenital stationary night blindness, which affects the
      photoreceptoral signal transmission. The results indicate that, under suitable
      conditions, the method proposed here has the potential to provide a powerful tool
      for routine clinical examinations, since it is able to recognize with high level
      of confidence the eventual presence of one of the two pathologies. 

PMID- 24923414
TI  - Emotion-specific load disrupts concomitant affective processing.
AB  - Findings in the neuroimaging literature suggest that separate brain circuitries
      are involved when individuals perform emotional compared to nonemotional working
      memory (WM) tasks. Here we test this hypothesis with behavioural measures. We
      predicted that the conceptual processing of affect would be disrupted more by
      concurrent affective than nonaffective load. Participants performed a conceptual
      task in which they verified affective versus sensory properties of concepts, and
      a second, concurrent, working memory (n-back) task in which the target stimuli
      were facial expressions. Results revealed that storing and updating affective (as
      compared with identity) features of facial expressions altered performance more
      for affective than for sensory properties of concepts. The findings are
      supportive of the ideas that affective resources exist and that these resources
      are specifically used during the processing and representation of affective
      properties of objects and events. 

PMID- 24923415
TI  - Regulation of crp gene expression by the catabolite repressor/activator, Cra, in
      Escherichia coli.
AB  - Growth of E. coli on several carbon sources is dependent on the catabolite
      repressor/activator (Cra) protein although a Cra consensus DNA-binding site is
      not present in the control regions of the relevant catabolic operons. We show
      that Cra regulates growth by activating expression of the crp gene. It thereby
      mediates catabolite repression of catabolic operons by an indirect mechanism.

PMID- 24923416
TI  - Expression of fibroblast growth factor 23 by canine soft tissue sarcomas.
AB  - Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of humans.
      Some mesenchymal tumours (often resembling haemangiopericytomas) express
      molecules that normally regulate phosphorus metabolism; most frequently,
      fibroblast growth factor 23. Patients develop renal phosphate wasting and
      inappropriately low serum concentrations of 1, 25 (OH)2 vitamin D3 , leading to
      osteomalacia. Surgical removal of the tumour is curative. The authors examined
      expression of canine fibroblast growth factor 23 in 49 soft tissue sarcomas, and
      control tissues from normal adult dogs. RNA extracted from bone or formalin
      fixed, paraffin-embedded tissues was analysed by end point and quantitative
      reverse transcriptase-polymerase chain reaction. Fibroblast growth factor 23
      expression was detected in bone, lung, kidney, lymph node and thymus. Fifteen of
      49 sarcomas (31%) expressed fibroblast growth factor 23, three of these had high
      relative expression and some features resembling phosphatonin-expressing
      mesenchymal tumours of humans. Further work is required to determine whether TIO
      may occur in dogs. 

PMID- 24923417
TI  - Risk-adapted partial larynx and/or carotid artery sparing modulated radiation
      therapy of glottic cancer.
AB  - BACKGROUND: To evaluate outcome in patients with glottic cancer treated with
      intensity-modulated radiotherapy (IMRT) and to show effectiveness of partial
      laryngeal- and/or carotid artery sparing in low to intermediate risk tumors.
      STUDY DESIGN: Retrospective analysis. MATERIAL AND METHODS: From 01/2004 to
      03/2013 77 consecutive patients presenting with glottic cancer were treated in
      our department with IMRT as definitive treatment. T-stages distributed as
      follows: T1: n = 17, T2: n = 24, T3: n = 15, T4: n = 13 and recurrences: 8
      patients. Concomitant systemic therapy was applied in 39 patients consisting of
      either cisplatin or cetuximab. RESULTS: Mean/median follow-up (FU) time was
      32.2/28 months (range: 4-98.7). Three year local control (LC), ultimate LRC and
      laryngectomy free survival rate was 77%, 92% and 80%, respectively. Three year
      overall survival of the entire cohort was 81%. Three year local control for
      T1/T2, T3/T4, and recurred tumors was 95%, 65%, and 38%, respectively. Three year
      overall survival was 86% for T1-4 stages, 55% for recurred disease, respectively.
      Partial laryngeal/carotid artery sparing was performed in all T1 patients (n =
      17) and 17/22 T2N0 patients. Rate of late sequels was low. CONCLUSION: IMRT for
      glottic cancer shows high control rates. In low to intermediate risk tumors an
      individualized treatment volume with partial larynx +/- carotid artery sparing is
      effective and holds the potential to reduce long term toxicity. The therapeutic
      outcome was not compromised.

PMID- 24923418
TI  - Is physiotherapy effective in the management of child and adolescent conversion
      disorder? A systematic review.
AB  - Child and adolescent conversion disorder has the potential to impart significant
      burden on health-care services and affect quality of life. Clinically,
      physiotherapists are involved in conversion disorder management; however, no
      systematic reviews have examined physiotherapy effectiveness in its management.
      The aim of this review is to identify the efficacy of physiotherapy management of
      child and adolescent conversion disorder. A search of multiple databases
      (Medline, CINAHL, Embase, PsychINFO, PEDro and the Cochrane Library) was
      completed along with manual searching of relevant reference lists to identify
      articles including children 0-18 years with a diagnosis of conversion disorder
      who received physical management. Two independent reviewers screened titles and
      abstracts using criteria. Data were extracted regarding study characteristics,
      functional outcome measures, length of stay, physiotherapy service duration and
      resolution of conversion symptoms. Methodological quality was assessed using a
      tool designed for observational studies. Twelve observational studies were
      included. No functional outcome measures were used to assess the effectiveness of
      the treatment protocols in the case studies. Resolution of symptoms occurred in
      all but two cases, with conversion symptoms still present at 11 months and at 2
      years. Length of stay varied from 3 days to 16 weeks, with similar variation
      evident in length of physiotherapy service provision (2.5 weeks to 16 weeks).
      There was limited and poor quality evidence to establish the efficacy of
      physiotherapy management of child and adolescent conversion disorders. More
      rigorous study designs with consistent use of reliable, valid and sensitive
      functional outcome measures are needed in this area. 

PMID- 24923419
TI  - Probing the coordination properties of glutathione with transition metal ions
      (Cr2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+) by density functional
      theory.
AB  - Complexes formed by reduced glutathione (GSH) with metal cations (Cr(2+),
      Mn(2+),Fe(2+),Co(2+),Ni(2+),Cu(2+),Zn(2+),Cd(2+),Hg(2+)) were systematically
      investigated by the density functional theory (DFT). The results showed that the
      interactions of the metal cations with GSH resulted in nine different stable
      complexes and many factors had an effect on the binding energy. Generally, for
      the same period of metal ions, the binding energies ranked in the order of
      Cu(2+)>Ni(2+)>Co(2+)>Fe(2+)>Cr(2+)>Zn(2+)>Mn(2+); and for the same group of metal
      ions, the general trend of binding energies was Zn(2+)>Hg(2+)>Cd(2+). Moreover,
      the amounts of charge transferred from S or N to transition metal cations are
      greater than that of O atoms. For Fe(2+),Co(2+),Ni(2+),Cu(2+),Zn(2+),Cd(2+) and
      Hg(2+) complexes, the values of the Wiberg bond indices (WBIs) of M-S (M denotes
      metal cations) were larger than that of M-N and M-O; for Cr(2+) complexes, most
      of the WBIs of M-O in complexes were higher than that of M-S and M-N.
      Furthermore, the changes in the electron configuration of the metal cations
      before and after chelate reaction revealed that Cu(2+), Ni(2+),Co(2+) and Hg(2+)
      had obvious tendencies to be reduced to Cu(+),Ni(+),Co(+) and Hg(+) during the
      coordination process. 

PMID- 24923420
TI  - Idiopathic angioedema and urticarial vasculitis in a patient with a history of
      acquired haemophilia.

PMID- 24923423
TI  - Visibility from roads predict the distribution of invasive fishes in agricultural
      ponds.
AB  - Propagule pressure and habitat characteristics are important factors used to
      predict the distribution of invasive alien species. For species exhibiting strong
      propagule pressure because of human-mediated introduction of species, indicators
      of introduction potential must represent the behavioral characteristics of
      humans. This study examined 64 agricultural ponds to assess the visibility of
      ponds from surrounding roads and its value as a surrogate of propagule pressure
      to explain the presence and absence of two invasive fish species. A three
      dimensional viewshed analysis using a geographic information system quantified
      the visual exposure of respective ponds to humans. Binary classification trees
      were developed as a function of their visibility from roads, as well as five
      environmental factors: river density, connectivity with upstream dam reservoirs,
      pond area, chlorophyll a concentration, and pond drainage. Traditional indicators
      of human-mediated introduction (road density and proportion of urban land-use
      area) were alternatively included for comparison instead of visual exposure. The
      presence of Bluegill (Lepomis macrochirus) was predicted by the ponds' higher
      visibility from roads and pond connection with upstream dam reservoirs. Results
      suggest that fish stocking into ponds and their dispersal from upstream sources
      facilitated species establishment. Largemouth bass (Micropterus salmoides)
      distribution was constrained by chlorophyll a concentration, suggesting their
      lower adaptability to various environments than that of Bluegill. Based on
      misclassifications from classification trees for Bluegill, pond visual exposure
      to roads showed greater predictive capability than traditional indicators of
      human-mediated introduction. Pond visibility is an effective predictor of
      invasive species distribution. Its wider use might improve management and
      mitigate further invasion. The visual exposure of recipient ecosystems to humans
      is important for many invasive species that spread with frequent instances of
      human-mediated introduction. 

PMID- 24923421
TI  - The gray matter volume of the amygdala is correlated with the perception of
      melodic intervals: a voxel-based morphometry study.
AB  - Music is not simply a series of organized pitches, rhythms, and timbres, it is
      capable of evoking emotions. In the present study, voxel-based morphometry (VBM)
      was employed to explore the neural basis that may link music to emotion. To do
      this, we identified the neuroanatomical correlates of the ability to extract
      pitch interval size in a music segment (i.e., interval perception) in a large
      population of healthy young adults (N = 264). Behaviorally, we found that
      interval perception was correlated with daily emotional experiences, indicating
      the intrinsic link between music and emotion. Neurally, and as expected, we found
      that interval perception was positively correlated with the gray matter volume
      (GMV) of the bilateral temporal cortex. More important, a larger GMV of the
      bilateral amygdala was associated with better interval perception, suggesting
      that the amygdala, which is the neural substrate of emotional processing, is also
      involved in music processing. In sum, our study provides one of first
      neuroanatomical evidence on the association between the amygdala and music, which
      contributes to our understanding of exactly how music evokes emotional responses.

PMID- 24923424
TI  - Anhydrobiosis in yeast: FT-IR spectroscopic studies of yeast grown under
      conditions of severe oxygen limitation.
AB  - Anhydrobiosis is a unique state of living organisms when metabolism is
      temporarily and reversibly delayed in response to the extreme desiccation of
      cells. The production of dry active preparations of yeast grown under anaerobic
      conditions is not currently possible because preparations are extremely sensitive
      to the dehydration procedure, though they could be very helpful in different
      biotechnological processes, including bioethanol production. To characterize
      mechanisms responsible for such sensitivity to the dehydration procedure, Fourier
      transform infrared spectroscopy was used to study the composition of aerobically
      grown yeast Saccharomyces cerevisiae resistant to dehydration and grown under
      conditions of severe oxygen limitation and sensitive to dehydration. Results
      indicated that significantly lower amounts of lipids in cells, grown under
      conditions of severe oxygen limitation, may be related to the mechanisms of
      sensitivity. Dehydration of both resistant and sensitive S. cerevisiae cells was
      accompanied by similar changes in main cellular compounds. Amounts of nucleic
      acids and proteins decreased slightly, whereas that of lipids and carbohydrates
      increased. Artificially reduced sensitivity to dehydration in S. cerevisiae
      cells, grown under conditions of severe oxygen limitation, led to the increase in
      the lipid concentration. The chemical composition of S. cerevisiae membranes is
      proposed to dictate the resistance to dehydration in resistant and sensitive
      cells. 

PMID- 24923427
TI  - Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor
      growth in mice.
AB  - BACKGROUND: Breast cancer is one of the most deadly diseases in women. Inhibiting
      the synthesis of estrogen is effective in treating patients with estrogen
      responsive breast cancer. Previous studies have demonstrated that use of
      cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk.
      METHODS: In the present study, we employed an established mouse model for
      postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2
      inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into
      ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or
      aspirin at 200 ppm by oral administration with androstenedione injection.
      RESULTS: Our results showed that both COX inhibitors could suppress the cancer
      xenograft growth without changing the plasma estrogen level. Protein expression
      of ERalpha, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor
      samples, whereas only Bcl-xL expression was suppressed in those treated with
      aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated
      in samples treated with celecoxib. Further studies in culture cells verified that
      the increase in miR-222 expression might contribute to ERalpha downregulation but
      not the growth deterrence of cells. CONCLUSION: Overall, this study suggested
      that both celecoxib and aspirin could prevent breast cancer growth by regulating
      proteins in the cell cycle and apoptosis without blocking estrogen synthesis.
      Besides, celecoxib might affect miR expression in an undesirable fashion.

PMID- 24923426
TI  - Tug-of-war of microtubule filaments at the boundary of a kinesin- and dynein
      patterned surface.
AB  - Intracellular cargo is transported by multiple motor proteins. Because of the
      force balance of motors with mixed polarities, cargo moves bidirectionally to
      achieve biological functions. Here, we propose a microtubule gliding assay for a
      tug-of-war study of kinesin and dynein. A boundary of the two motor groups is
      created by photolithographically patterning gold to selectively attach kinesin to
      the glass and dynein to the gold surface using a self-assembled monolayer. The
      relationship between the ratio of two antagonistic motor numbers and the velocity
      is derived from a force-velocity relationship for each motor to calculate the
      detachment force and motor backward velocity. Although the tug-of-war involves
      >100 motors, values are calculated for a single molecule and reflect the
      collective dynein and non-collective kinesin functions when they work as a team.
      This assay would be useful for detailed in vitro analysis of intracellular
      motility, e.g., mitosis, where a large number of motors with mixed polarities are
      involved. 

PMID- 24923425
TI  - Reference values and age and sex differences in physical performance measures for
      community-dwelling older Japanese: a pooled analysis of six cohort studies.
AB  - OBJECTIVES: To determine age- and sex-specific reference values for six physical
      performance measures, i.e. hand-grip strength, one-legged stance, and gait speed
      and step length at both usual and maximum paces, and to investigate age and sex
      differences in these measures among community-dwelling older Japanese adults.
      METHODS: We conducted a pooled analysis of data from six cohort studies collected
      between 2002 and 2011 as part of the Tokyo Metropolitan Institute of Gerontology
      Longitudinal Interdisciplinary Study on Aging. The pooled analysis included cross
      sectional data from 4683 nondisabled, community-dwelling adults aged 65 years or
      older (2168 men, 2515 women; mean age: 74.0 years in men and 73.9 years in
      women). RESULTS: Unweighted simple mean (standard deviation) hand-grip strength,
      one-legged stance, usual gait speed, usual gait step length, maximum gait speed,
      and maximum gait step length were 31.7 (6.7) kg, 39.3 (23.0) s, 1.29 (0.25) m/s,
      67.7 (10.0) cm, 1.94 (0.38) m/s, and 82.3 (11.6) cm, respectively, in men and
      20.4 (5.0) kg, 36.8 (23.4) s, 1.25 (0.27) m/s, 60.8 (10.0) cm, 1.73 (0.36) m/s,
      and 69.7 (10.8) cm, respectively, in women. All physical performance measures
      showed significant decreasing trends with advancing age in both sexes (all
      P<0.001 for trend). We also constructed age- and sex-specific appraisal standards
      according to quintiles. With increasing age, the sex difference in hand-grip
      strength decreased significantly (P<0.001 for age and sex interaction). In
      contrast, sex differences significantly increased in all other measures (all
      P<0.05 for interactions) except step length at maximum pace. CONCLUSION: Our
      pooled analysis yielded inclusive age- and sex-specific reference values and
      appraisal standards for major physical performance measures in nondisabled,
      community-dwelling, older Japanese adults. The characteristics of age-related
      decline in physical performance measures differed between sexes.

PMID- 24923428
TI  - S100B protein activates a RAGE-dependent autocrine loop in astrocytes:
      implications for its role in the propagation of reactive gliosis.
AB  - Extracellular S100B dramatically increases after brain injury. While low S100B
      levels are neuroprotective, micromolar S100B levels have shown in vitro to
      activate microglia and facilitate neuronal death. In astrocytes, S100B exposure
      activates nuclear factor kappa B (NF-kappaB) and induces pro-inflammatory
      mediators. On microglia and neurons S100B effects are essentially mediated by
      receptor for advanced glycation end products (RAGE)/NF-kappaB, but it is not
      clear if these intracellular cascades are activated by different S100B levels in
      astrocytes and whether increased extracellular S100B is sufficient to induce
      reactive gliosis. A better understanding of these pathways is essential for
      developing successful strategies to preserve the beneficial S100B effects after
      brain injury. Here, we show that microglia-depleted cultured astrocytes exposed
      to S100B mimicked several features of reactive gliosis by activating RAGE/Rac-1
      Cdc42, RAGE/Erk-Akt or RAGE/NF-kappaB-dependent pathways. S100B effects include
      RAGE/Rac1-Cdc42-dependent astroglial hypertrophy and facilitation of migration as
      well as increased mitosis. S100B exposure improved the astrocytic survival to
      oxidative stress, an effect that requires Erk/Akt. S100B also activates NF-kappaB
      in a dose-dependent manner; increases RAGE proximal promoter transcriptional
      activity and augmented endogenous RAGE expression. S100B-exposed astrocytes
      showed a pro-inflammatory phenotype with expression of Toll-like receptor 2 (TLR
      2), inducible nitric oxide synthase (iNOS) and interleukin 1-beta (IL-1beta), and
      facilitated neuronal death induced by oxygen-glucose deprivation. In vivo,
      intracerebral infusion of S100B was enough to induce an astroglial reactive
      phenotype. Together, these findings demonstrate that extracellular S100B in the
      micromolar level activates different RAGE-dependent pathways that turn astrocytes
      into a pro-inflammatory and neurodegenerative phenotype. We propose that S100B
      turns astrocytes into a reactive phenotype in a RAGE-dependent manner but
      engaging different intracellular pathways. While both nanomolar and micromolar
      S100B turn astrocytes into a reactive phenotype, micromolar S100B induces a
      conversion into a pro-inflammatory-neurodegenerative profile that facilitates
      neuronal death of OGD-exposed neurons. We think that S100B/RAGE interaction is
      essential to expand reactive gliosis in the injured brain being a tempting target
      for limiting reactive gliosis to prevent the glial conversion into the
      neurodegenerative profile. 

PMID- 24923429
TI  - Functional diversification of duplicated CYC2 clade genes in regulation of
      inflorescence development in Gerbera hybrida (Asteraceae).
AB  - The complex inflorescences (capitula) of Asteraceae consist of different types of
      flowers. In Gerbera hybrida (gerbera), the peripheral ray flowers are bilaterally
      symmetrical and lack functional stamens while the central disc flowers are more
      radially symmetrical and hermaphroditic. Proteins of the CYC2 subclade of the
      CYC/TB1-like TCP domain transcription factors have been recruited several times
      independently for parallel evolution of bilaterally symmetrical flowers in
      various angiosperm plant lineages, and have also been shown to regulate flower
      type identity in Asteraceae. The CYC2 subclade genes in gerbera show largely
      overlapping gene expression patterns. At the level of single flowers, their
      expression domain in petals shows a spatial shift from the dorsal pattern known
      so far in species with bilaterally symmetrical flowers, suggesting that this
      change in expression may have evolved after the origin of Asteraceae. Functional
      analysis indicates that GhCYC2, GhCYC3 and GhCYC4 mediate positional information
      at the proximal-distal axis of the inflorescence, leading to differentiation of
      ray flowers, but that they also regulate ray flower petal growth by affecting
      cell proliferation until the final size and shape of the petals is reached.
      Moreover, our data show functional diversification for the GhCYC5 gene. Ectopic
      activation of GhCYC5 increases flower density in the inflorescence, suggesting
      that GhCYC5 may promote the flower initiation rate during expansion of the
      capitulum. Our data thus indicate that modification of the ancestral network of
      TCP factors has, through gene duplications, led to the establishment of new
      expression domains and to functional diversification. 

PMID- 24923430
TI  - Impact of living and socioeconomic characteristics on cardiovascular risk in
      ischemic stroke patients.
AB  - OBJECTIVE: We aimed to stratify the risk of vascular event recurrence in patients
      with cerebral infarction according to living and socioeconomic characteristics
      and geographic region. METHOD: The Outcomes in Patients with TIA and
      Cerebrovascular Disease (OPTIC) study is an international prospective study of
      patients aged 45 years or older who required secondary prevention of stroke
      [following either an acute transient ischemic attack, minor ischemic strokes, or
      recent (less than six-months previous), stable, first-ever, nondisabling ischemic
      stroke]. A total 3635 patients from 245 centers in 17 countries in four regions
      (Latin America, Middle East, North Africa, South Africa) were enrolled between
      2007 and 2008. The outcome measure was the two-year rate of a composite of major
      vascular events (vascular death, myocardial infarction and stroke). RESULTS:
      During the two-year follow-up period, 516 patients experienced at least one major
      cardiovascular event, resulting in an event rate of 15.6% (95% confidence
      interval 14.4-16.9%). Event rates varied across geographical region (P < 0.001),
      ranging from 13.0% in Latin America to 20.7% in North Africa. Unemployment
      status, living in a rural area, not living in fully serviced accommodation (i.e.,
      house or apartment with its own electricity, toilet and water supply), no health
      insurance coverage, and low educational level (less than two-years of schooling)
      were predictors of major vascular events. Major vascular event rates steeply
      increased with the number of low-quality living/socioeconomic conditions (from
      13.4% to 47.9%, adjusted P value for trend <0.001). CONCLUSION: Vascular risk in
      stroke patients in low- and middle-income countries varies not only with the
      number of arterial beds involved but also with socioeconomic variables.

PMID- 24923431
TI  - The relationship between feed efficiency and the circadian profile of blood
      plasma analytes measured in beef heifers at different physiological stages.
AB  - The characterization of blood metabolite concentrations over the circadian period
      and across physiological stages is important for understanding the biological
      basis of feed efficiency, and may culminate in indirect methods for assessing
      feed efficiency. Hematological analyses for albumin, urea, creatine kinase,
      glutamate dehydrogenase, aspartate aminotransferase, carbon dioxide, and acetate
      were carried out in growing and gestating heifers. These measures were carried
      out in a sample of 36 Bos taurus crossed beef heifers held under the same
      husbandry conditions. Hourly blood samples were collected over a 24-h period on
      three separate sampling occasions, corresponding approximately to the yearling
      (and open), early-gestation and late-gestation stages. This design was used to
      determine variation throughout the day, effects due to physiological status and
      any associations with feed efficiency, as measured by residual feed intake. Blood
      analyte levels varied with time of day, with the most variation occurring between
      0800 and 1600 h. There were also considerable differences in analyte levels
      across the three physiological stages; for example, creatine kinase was higher
      (P<0.05) in open heifers, followed by early- and late-gestation heifers. Feed
      efficiency was also associated with analyte abundance. In more feed-efficient
      open heifers, there were higher activities of creatine kinase (P<0.05) and
      aspartate aminotransferase (P<0.05), and lower concentrations of carbon dioxide
      (P<0.05). Furthermore, in late gestation, more efficient heifers had lower urea
      concentrations (P<0.05) and lower creatine kinase levels (P<0.05). Over the whole
      experimental period, carbon dioxide concentrations were numerically lower in more
      feed efficient heifers (P=0.079). Differences were also observed across
      physiological stages. For instance, open heifers had increased levels (P<0.05) of
      creatine kinase, aspartate aminotransferase, carbon dioxide than early and late
      pregnancy heifers. In essence, this study revealed relevant information about the
      metabolic profile in the context of feed efficiency and physiological stages.
      Further optimization of our approach, along with the evaluation of complementary
      analytes, will aid in the development of robust, indirect assessments of feed
      efficiency.

PMID- 24923432
TI  - Peanut allergens alter intestinal barrier permeability and tight junction
      localisation in Caco-2 cell cultures.
AB  - BACKGROUND/AIMS: Allergen absorption by epithelia may play an important role in
      downstream immune responses. Transport mechanisms that can bypass Peyer's patches
      include transcellular and paracellular transport. The capacity of an allergen to
      cross via these means can modulate downstream processing of the allergen by the
      immune system. The aim of this study was to investigate allergen-epithelial
      interactions of peanut allergens with the human intestinal epithelium. METHODS:
      We achieved this using the human Caco-2 cell culture model, exposed to crude
      peanut extract. Western and immunofluorescence analysis were used to identify the
      cellular and molecular changes of peanut extract on the intestinal epithelium.
      RESULTS: Following exposure of Caco-2 cells to peanut extract, binding of the
      peanut allergens Ara h 1 and Ara h 2 to the apical cellular membrane and
      transcytosis across the monolayers were observed. Additionally, the co
      localisation of the transmembrane tight junction proteins occludin, JAM-A and
      claudin-1, with the intracellular adhesion protein ZO-1 was modified. CONCLUSION:
      Disruption of Caco-2 barrier integrity through tight junction disruption may
      enable movement of peanut proteins across the intestinal epithelium. This
      accounts for peanut's increased allergenicity, compared to other food allergens,
      and provides an explanation for the potency of peanut allergens in immune
      response elicitation.

PMID- 24923433
TI  - Child's assent in research: age threshold or personalisation?
AB  - BACKGROUND: Assent is an important ethical and legal requirement of paediatric
      research. Unfortunately, there are significant differences between the guidelines
      on the details of assent. DISCUSSION: What often remains unclear is the scope of
      the assent, the procedure for acquiring it, and the way in which children's
      capacity to assent is determined. There is a general growing tendency that
      suggests that the process of assent should be personalised, that is, tailored to
      a particular child. This article supports the idea of personalisation. However,
      we also propose placing limits on personalisation by introducing a suggested
      requirement of assent starting at a school-age threshold. In some situations
      RECs/IRBs and researchers could reduce the suggested threshold. SUMMARY: A
      recommended age threshold is likely to serve the interests of children better
      than ambiguous and flexible criteria for personalised age determination.

PMID- 24923434
TI  - Child and family adjustment following pediatric solid organ transplantation:
      factors to consider during the early years post-transplant.
AB  - Adjusting to life after transplant can be challenging to pediatric solid organ
      transplant recipients and their families. In this review, we discuss a number of
      important factors to consider during the first 2-3 yr after transplant (defined
      as the "early years"), including transitioning from hospital to home, returning
      to physical activity, feeding and nutrition, school reentry, potential cognitive
      effects of transplant, family functioning, and QOL. We highlight steps that
      providers can take to optimize child and family adjustment during this period. 

PMID- 24923435
TI  - Analysis of structural diversity in wolf-like canids reveals post-domestication
      variants.
AB  - BACKGROUND: Although a variety of genetic changes have been implicated in causing
      phenotypic differences among dogs, the role of copy number variants (CNVs) and
      their impact on phenotypic variation is still poorly understood. Further, very
      limited knowledge exists on structural variation in the gray wolf, the ancestor
      of the dog, or other closely related wild canids. Documenting CNVs variation in
      wild canids is essential to identify ancestral states and variation that may have
      appeared after domestication. RESULTS: In this work, we genotyped 1,611 dog CNVs
      in 23 wolf-like canids (4 purebred dogs, one dingo, 15 gray wolves, one red wolf,
      one coyote and one golden jackal) to identify CNVs that may have arisen after
      domestication. We have found an increase in GC-rich regions close to the
      breakpoints and around 1 kb away from them suggesting that some common motifs
      might be associated with the formation of CNVs. Among the CNV regions that showed
      the largest differentiation between dogs and wild canids we found 12 genes, nine
      of which are related to two known functions associated with dog domestication;
      growth (PDE4D, CRTC3 and NEB) and neurological function (PDE4D, EML5, ZNF500,
      SLC6A11, ELAVL2, RGS7 and CTSB). CONCLUSIONS: Our results provide insight into
      the evolution of structural variation in canines, where recombination is not
      regulated by PRDM9 due to the inactivation of this gene. We also identified genes
      within the most differentiated CNV regions between dogs and wolves, which could
      reflect selection during the domestication process.

PMID- 24923437
TI  - A rapid method of species identification of wild chironomids (Diptera:
      Chironomidae) via electrophoresis of hemoglobin proteins in sodium dodecyl
      sulfate polyacrylamide gel (SDS-PAGE).
AB  - Studying aquatic benthic macroinvertebrates (BMIs) in the field requires accurate
      taxonomic identification, which can be difficult and time consuming.
      Conventionally, head capsule morphology has been used to identify wild larvae of
      Chironomidae. However, due to the number of species and possible damage and/or
      deformity of their head capsules, another supporting approach for identification
      is needed. Here, we provide hemoglobin (Hb) protein in hemolymph of chironomids
      as a new biomarker that may help resolve some of the ambiguities and difficulties
      encountered during taxonomic identification. Chironomids collected from two
      locations in Maine and New Jersey, USA were identified to the genus level and in
      some cases to the species-level using head capsule and body morphologies. The
      head capsule for a particular individual was then associated with a corresponding
      Hb protein profile generated from sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). Distinct Hb profiles were observed from one group
      (Thienemannimyia) and four genera (Chironomus, Cricotopus, Dicrotendipes, and
      Glyptotendipes) of chironomids. Several species were polymorphic, having more
      than one Hb profile and/or having bands of the same size as those of other
      species. However, major bands and the combination of bands could distinguish
      individuals at the genus and sometimes species-level. Overall, this study showed
      that Hb profiles can be used in combination with head capsule morphology to
      identify wild chironomids.

PMID- 24923436
TI  - Evaluation of peripheral versus central effects of GABA(B) receptor activation
      using a novel, positive allosteric modulator of the GABA(B) receptor ADX71943, a
      pharmacological tool compound with a fully peripheral activity profile.
AB  - BACKGROUND AND PURPOSE: The GABA(B) receptor agonist, baclofen, has shown
      promising effects in patients suffering from pain, post-traumatic stress
      disorder, alcoholism, overactive bladder and gastroesophageal reflux disease.
      However, baclofen's short duration of action and side effects limit its wider
      use. Here we characterized a novel, GABA(B) receptor positive allosteric
      modulator (PAM) ADX71943. EXPERIMENTAL APPROACH: In vitro, ADX71943 was assessed
      for pharmacological activity and selectivity using recombinant and native GABA(B)
      receptors. In vivo ADX71943 was assessed in the acetic acid-induced writhing
      (AAW) test in mice and formalin tests (FTs) in mice and rats. Marble burying (MB)
      and elevated plus maze (EPM) tests, rotarod, spontaneous locomotor activity
      (sLMA) and body temperature (BT) tests in mice and rats were used to investigate
      centrally-mediated effects. KEY RESULTS: In vitro, in the presence of GABA,
      ADX71943 increased the potency and efficacy of agonists and showed selectivity at
      the GABA(B) receptor. ADX71943 reduced pain-associated behaviours in AAW; an
      effect blocked by GABA(B) receptor antagonist CGP63360. ADX71943 reduced pain in
      the FT in mice and rats, but was inactive in the MB and EPM despite reaching high
      concentrations in plasma. ADX71943 had no effect on BT, rotarod and sLMA.
      CONCLUSIONS AND IMPLICATIONS: ADX71943 showed consistent and target-related
      efficacy in tests of disorders that have a significant peripheral component
      (acute and chronic pain), while having no effect in those associated with
      centrally-mediated anxiety-like reactivity and side effects. Thus, ADX71943 is a
      useful pharmacological tool for delineation of peripherally- versus centrally
      mediated effects of GABA(B) receptor activation.

PMID- 24923438
TI  - Specific behaviour, mood and personality traits may contribute to obesity in
      patients with craniopharyngioma.
AB  - INTRODUCTION: Patients with craniopharyngioma (CP) often suffer from obesity, but
      the underlying causes are still not fully understood. We compared CP to patients
      with nonfunctioning pituitary adenoma (NFPA) and to a control group (CG) using
      standardized questionnaires to investigate whether behavioural, mood or
      personality traits contribute to obesity. METHODS: We compared 31 patients with
      CP (42% male, 53 +/- 15.1 years) to 26 patients with NFPA (71% male, 63.2 +/-
      10.3 years) and to age- and gender-matched local CG (ratio 2:1). Normative data
      from the literature are included for reference. Patients were asked to complete
      eleven standardized questionnaires. Two questionnaires were used to evaluate
      eating disorders (FEV, EDE-Q), one depression (BDI), one anxiety (STAI), three
      health-related quality of life (SF-36, EuroQoL, QoL-AGHDA), one sleepiness
      (Epworth Sleepiness Scale), two personality (EPQ-RK, TPQ) and one body image (FKB
      20). RESULTS: Patients with CP scored significantly higher in conscious hunger
      perception (FEV, CP 5.8 +/- 3.2 scores, NFPA 3.6 +/- 3.3 scores, CG 3.0 +/- 2.5,
      P < 0.001). They had similar scores for BDI compared with NFPA, but higher scores
      to CG (P < 0.001, CP 10.6 +/- 8.3, NFPA 7.5 +/- 5.7, CG 4.96 +/- 4.2). CP and
      NFPA scored higher than CG for anxiety and personality traits such as harm
      avoidance, fatigability and asthenia and slightly higher for neuroticism. No
      differences were seen for EDE-Q, quality of life, daytime sleepiness and body
      image between CP and NFPA. However, differences could be observed to normative
      data from the literature. CONCLUSION: Obesity in patients with CP might be
      influenced by eating disorders, negative mood alterations and increased anxiety
      related personality traits.

PMID- 24923439
TI  - Effects of liposome-encapsulated hemoglobin on gastric wound healing in the rat.
AB  - Liposome-encapsulated hemoglobin (LEH) may improve microcirculation and oxygen
      (O2 ) metabolism at a surgical wound to accelerate its healing. Ten mL/kg of LEH
      with high (h-LEH) or low O2 -affinity (l-LEH), homologous red blood cells (RBC),
      empty liposome or saline as a control was infused before a 10-mm incision and
      interrupted suture closure of the gastric wall in a total of 110 rats. Two and 4
      days later, the stomach was excised for bursting pressure determination and
      histological sampling. The dose-response relationship was examined in 70
      additional rats receiving progressively reduced doses of h-LEH. Hypoxia-inducible
      factor-1alpha (HIF-1alpha) was stained immunohistochemically in 54 other rats to
      examine its accumulation at the anastomotic sites. Bursting pressure of the
      surgical wound was significantly higher 2 days after surgery only in the h-LEH
      treated rats (P < 0.05), but not at 4 days after surgery, when other rats showed
      increased bursting pressure to a nonsignificant level. Histological examination
      revealed less granulocyte infiltration, better granulation, and more macrophage
      infiltration in h-LEH-treated rats at 2 days, but no longer at 4 days
      postsurgery. Dose-response study revealed that 0.4 mL/kg of h-LEH (hemoglobin 24
      mg/kg) was effective for elevating bursting pressure at 2 days. h-LEH-treated
      rats had significantly suppressed HIF-1alpha accumulation in the wound 6, 24, and
      48 h after surgery as compared with control animals treated with homologous RBC
      or saline. In conclusion, the results suggest that h-LEH, but not l-LEH or
      homologous transfusion, may accelerate wound healing early after gastric incision
      and anastomosis in the rat. The mechanism(s) appears to be related to improved O2
      supply, aerobic metabolism, and suppressed inflammation in the wound. 

PMID- 24923440
TI  - Pleiotropic effects of the rho-kinase inhibitor fasudil after subarachnoid
      hemorrhage: a review of preclinical and clinical studies.
AB  - There is growing evidence that Rho-kinase contributes to cardiovascular disease,
      which has made Rho-kinase a target for the treatment of human diseases. To date,
      the only Rho-kinase inhibitor employed clinically in humans is fasudil, which has
      been used for the prevention of cerebral vasospasm and subsequent ischemic injury
      after surgery for subarachnoid hemorrhage (SAH). A number of pathological
      processes, in particular hemodynamic dysfunctions and inflammatory reactions, are
      thought to be related in the pathogenesis of delayed cerebral vasospasm and
      subsequent ischemic injury after SAH. This review focuses on fasudil's
      pleiotropic therapeutic effects: amelioration of hemodynamic dysfunction and
      inflammation, and discusses in detail the clinical studies on fasudil
      administered after the occurrence of SAH. 

PMID- 24923441
TI  - Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte
      transformation and tumor growth.
AB  - Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor
      prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and
      G-CIMP-subtypes enrich distinct classes of biological processes. One of the
      hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to
      be down-regulated in GBM. Promoter hypermethylation of ULK2 was confirmed by
      bisulfite sequencing. GBM and glioma cell lines had low levels of ULK2
      transcripts, which could be reversed upon methylation inhibitor treatment. ULK2
      promoter methylation and transcript levels showed significant negative
      correlation. Ectopic overexpression of ULK2-induced autophagy, which further
      enhanced upon nutrient starvation or temozolomide chemotherapy. ULK2 also
      inhibited the growth of glioma cells, which required autophagy induction as
      kinase mutant of ULK2 failed to induce autophagy and inhibit growth. Furthermore,
      ULK2 induced autophagy and inhibited growth in Ras-transformed immortalized Baby
      Mouse Kidney (iBMK) ATG5(+/+) but not in autophagy-deficient ATG5(-/-) cells.
      Growth inhibition due to ULK2 induced high levels of autophagy under starvation
      or chemotherapy utilized apoptotic cell death but not at low levels of autophagy.
      Growth inhibition by ULK2 also appears to involve catalase degradation and
      reactive oxygen species generation. ULK2 overexpression inhibited anchorage
      independent growth, inhibited astrocyte transformation in vitro and tumor growth
      in vivo. Of all autophagy genes, we found ULK2 and its homologue ULK1 were only
      down-regulated in all grades of glioma. Thus these results altogether suggest
      that inhibition of autophagy by ULK1/2 down-regulation is essential for glioma
      development. 

PMID- 24923442
TI  - The nutrient stress-induced small GTPase Rab5 contributes to the activation of
      vesicle trafficking and vacuolar activity.
AB  - Rab family small GTPases regulate membrane trafficking by spatiotemporal
      recruitment of various effectors. However, it remains largely unclear how the
      expression and functions of Rab proteins are regulated in response to
      extracellular or intracellular stimuli. Here we show that Ypt53, one isoform of
      Rab5 in Saccharomyces cerevisiae, is up-regulated significantly under nutrient
      stress. Under non-stress conditions, Vps21, a constitutively expressed Rab5
      isoform, is crucial to Golgi-vacuole trafficking and to vacuolar hydrolase
      activity. However, when cells are exposed to nutrient stress for an extended
      period of time, the up-regulated Ypt53 and the constitutive Vps21 function
      redundantly to maintain these activities, which, in turn, prevent the
      accumulation of reactive oxygen species and maintain mitochondrial respiration.
      Together, our results clarify the relative roles of these constitutive and
      nutrient stress-inducible Rab5 proteins that ensure adaptable vesicle trafficking
      and vacuolar hydrolase activity, thereby allowing cells to adapt to environmental
      changes.

PMID- 24923443
TI  - Ubiquitin-specific peptidase 20 regulates Rad17 stability, checkpoint kinase 1
      phosphorylation and DNA repair by homologous recombination.
AB  - Rad17 is a subunit of the Rad9-Hus1-Rad1 clamp loader complex, which is required
      for Chk1 activation after DNA damage. Rad17 has been shown to be regulated by the
      ubiquitin-proteasome system. We have identified a deubiquitylase, USP20 that is
      required for Rad17 protein stability in the steady-state and post DNA damage. We
      demonstrate that USP20 and Rad17 interact, and that this interaction is enhanced
      by UV exposure. We show that USP20 regulation of Rad17 is at the protein level in
      a proteasome-dependent manner. USP20 depletion results in poor activation of Chk1
      protein by phosphorylation, consistent with Rad17 role in ATR-mediated
      phosphorylation of Chk1. Similar to other DNA repair proteins, USP20 is
      phosphorylated post DNA damage, and its depletion sensitizes cancer cells to
      damaging agents that form blocks ahead of the replication forks. Similar to Chk1
      and Rad17, which enhance recombinational repair of collapsed replication forks,
      we demonstrate that USP20 depletion impairs DNA double strand break repair by
      homologous recombination. Together, our data establish a new function of USP20 in
      genome maintenance and DNA repair. 

PMID- 24923444
TI  - c-Abl activates janus kinase 2 in normal hematopoietic cells.
AB  - Jak2 is involved in cytokine growth factor-stimulated signal transduction, but
      the mechanism of its activation is largely unknown. Here, we investigated Jak2
      activation in a normal hematopoietic cell line, 32D mouse myeloid cells. The
      bimolecular fluorescence complementation studies showed that c-Abl formed a
      stable complex with Jak2 in live cells. Co-immunoprecipitation results showed
      that c-Abl bound to the betac chain of IL-3/IL-5/GM-CSF receptors. The kinase
      activities of both c-Abl and Jak2 were stimulated by IL-3 in 32D cells.
      Decreasing c-Abl protein expression in 32D cells by inducible shRNA decreased
      Jak2 activity and resulted in the failure of Jak2 activation in response to IL-3.
      Treatment of IL-3 and serum-starved 32D cells with 1 MUM imatinib mysylate
      inhibited IL-3 stimulated kinase activities of both c-Abl and Jak2. In addition,
      the kinase-deficient Bcr-Abl mutant (p210K1172R) was defective for activation of
      Jak2 in 32D cells and impaired IL-3 independent growth, which was rescued by
      overexpression of c-Abl (+Abl). IL-3 efficiently inhibited apoptosis of
      32Dp210K/R+Abl cells induced by imatinib mysylate but not Jak2 kinase inhibitor
      TG101209. In summary, our findings provide evidence that the kinase function of c
      Abl and its C-terminal CT4 region is crucial for its interaction with Jak2 and
      its activation. c-Abl kinase activity induced by IL-3 is required for IL-3
      stimulated Jak2 and Jak1 activation. Our findings reveal a novel regulatory role
      of c-Abl in Jak2 activation induced by IL-3 cytokine growth factor in 32D
      hematopoietic cells.

PMID- 24923445
TI  - The tumor suppressor chromodomain helicase DNA-binding protein 5 (CHD5) remodels
      nucleosomes by unwrapping.
AB  - Although mutations or deletions of chromodomain helicase DNA-binding protein 5
      (CHD5) have been linked to cancer and implicate CHD5 in tumor suppression, the
      ATP-dependent activity of CHD5 is currently unknown. In this study, we discovered
      that CHD5 is a chromatin remodeling factor with a unique enzymatic activity. CHD5
      can expose nucleosomal DNA at one or two discrete positions in the nucleosome.
      The exposure of the nucleosomal DNA by CHD5 is dependent on ATP hydrolysis, but
      continued ATP hydrolysis is not required to maintain the nucleosomes in their
      remodeled state. The activity of CHD5 is distinct from other related chromatin
      remodeling ATPases, such as ACF and BRG1, and does not lead to complete
      disruption or destabilization of the nucleosome. Rather, CHD5 likely initiates
      remodeling in a manner similar to that of other remodeling factors but does not
      significantly reposition the nucleosome. While the related factor CHD4 shows
      strong ATPase activity, it does not unwrap nucleosomes as efficiently as CHD5.
      Our findings add to the growing evidence that chromatin remodeling ATPases have
      diverse roles in modulating chromatin structure.

PMID- 24923446
TI  - The calcium-induced conformation and glycosylation of scavenger-rich cysteine
      repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction
      with antigen I/II homologs.
AB  - Oral streptococci adhere to tooth-immobilized glycoprotein 340 (GP340) via the
      surface protein antigen I/II (AgI/II) and its homologs as the first step in
      pathogenesis. Studying this interaction using recombinant proteins, we observed
      that calcium increases the conformational stability of the scavenger-rich
      cysteine repeat (SRCRs) domains of GP340. Our results also show that AgI/II
      adheres specifically with nanomolar affinity to the calcium-induced SRCR
      conformation in an immobilized state and not in solution. This interaction is
      significantly dependent on the O-linked carbohydrates present on the SRCRs. This
      study also establishes that a single SRCR domain of GP340 contains the two
      surfaces to which the apical and C-terminal regions of AgI/II noncompetitively
      adhere. Compared with the single SRCR domain, the three tandem SRCR domains
      displayed a collective/cooperative increase in their bacterial adherence and
      aggregation. The previously described SRCRP2 peptide that was shown to aggregate
      several oral streptococci displayed limited aggregation and also nonspecific
      adherence compared to SRCR domains. Finally, we show distinct species-specific
      adherence/aggregation between Streptococcus mutans AgI/II and Streptococcus
      gordonii SspB in their interaction with the SRCRs. This study concludes that
      identification of the metal ion and carbohydrate adherence motifs on both SRCRs
      and AgI/II homologs could lead to the development of anti-adhesive inhibitors
      that could deter the adherence of pathogenic oral streptococci and thereby
      prevent the onset of infections. 

PMID- 24923447
TI  - Nucleolar stress induces ubiquitination-independent proteasomal degradation of
      PICT1 protein.
AB  - The nucleolar protein PICT1 regulates tumor suppressor p53 by tethering ribosomal
      protein L11 within the nucleolus to repress the binding of L11 to the E3 ligase
      MDM2. PICT1 depletion results in the release of L11 to the nucleoplasm to inhibit
      MDM2, leading to p53 activation. Here, we demonstrate that nucleolar stress
      induces proteasome-mediated degradation of PICT1 in a ubiquitin-independent
      manner. Treatment of H1299 cells with nucleolar stress inducers, such as
      actinomycin D, 5-fluorouridine, or doxorubicin, induced the degradation of PICT1
      protein. The proteasome inhibitors MG132, lactacystin, and epoxomicin blocked
      PICT1 degradation, whereas the inhibition of E1 ubiquitin-activating enzyme by a
      specific inhibitor and genetic inactivation fail to repress PICT1 degradation. In
      addition, the 20 S proteasome was able to degrade purified PICT1 protein in
      vitro. We also found a PICT1 mutant showing nucleoplasmic localization did not
      undergo nucleolar stress-induced degradation, although the same mutant underwent
      in vitro degradation by the 20 S proteasome, suggesting that nucleolar
      localization is indispensable for the stress-induced PICT1 degradation. These
      results suggest that PICT1 employs atypical proteasome-mediated degradation
      machinery to sense nucleolar stress within the nucleolus.

PMID- 24923449
TI  - Direct observation of spin-forbidden transitions through the use of suitably
      polarized light.
AB  - The study of excited triplet states of a molecular system is a difficult task
      because accessing them involves forbidden transitions from the singlet ground
      state. Nevertheless, absorption spectra of many molecules present, at low
      energies, the weak fingerprint of these triplet states. At higher energies this
      information is usually masked by the intense signal of the singlet states. Here
      we show, for the specific case of the sulphur dioxide molecule, that the combined
      use of polarized light and molecular alignment can enhance the triplet part of
      the spectrum, even making it the only absorption process. 

PMID- 24923448
TI  - Structural and functional characterization of Escherichia coli toxin-antitoxin
      complex DinJ-YafQ.
AB  - Toxin YafQ functions as a ribonuclease in the dinJ-yafQ toxin-antitoxin system of
      Escherichia coli. Antitoxin DinJ neutralizes YafQ-mediated toxicity by forming a
      stable protein complex. Here, crystal structures of the (DinJ)2-(YafQ)2 complex
      and the isolated YafQ toxin have been determined. The structure of the
      heterotetrameric complex (DinJ)2-(YafQ)2 revealed that the N-terminal region of
      DinJ folds into a ribbon-helix-helix motif and dimerizes for DNA recognition, and
      the C-terminal portion of each DinJ exclusively wraps around a YafQ molecule.
      Upon incorporation into the heterotetrameric complex, a conformational change of
      YafQ in close proximity to the catalytic site of the typical microbial
      ribonuclease fold was observed and validated. Mutagenesis experiments revealed
      that a DinJ mutant restored YafQ RNase activity in a tetramer complex in vitro
      but not in vivo. An electrophoretic mobility shift assay showed that one of the
      palindromic sequences present in the upstream intergenic region of DinJ served as
      a binding sequences for both the DinJ-YafQ complex and the antitoxin DinJ alone.
      Based on structure-guided and site-directed mutagenesis of DinJ-YafQ, we showed
      that two pairs of amino acids in DinJ were important for DNA binding; the R8A and
      K16A substitutions and the S31A and R35A substitutions in DinJ abolished the DNA
      binding ability of the DinJ-YafQ complex. 

PMID- 24923450
TI  - Congenital duodenal stenosis misdiagnosed as iron deficiency anemia for 20 years.

PMID- 24923451
TI  - NOTCH1 mutations identify a chronic lymphocytic leukemia patient subset with
      worse prognosis in the setting of a rituximab-based induction and consolidation
      treatment.
AB  - Induction therapy with fludarabine followed by rituximab and consolidation plus
      maintenance with rituximab improved response duration (RD) and overall survival
      (OS) in our patients with chronic lymphocytic leukemia (CLL). The aim of our
      study was to investigate the clinical impact of NOTCH1 mutations in this setting
      of patients. The study included 123 progressive CLL patients homogeneously
      assigned to first-line induction treatment with fludarabine followed by
      rituximab. Fifty-nine patients either in complete remission (CR) minimal residual
      disease positive (MRD+) after induction (n = 39) or in partial remission (PR, n =
      20) underwent consolidation/maintenance therapy with rituximab. Sixteen patients
      in CR MRD + or PR underwent observation only. The presence of NOTCH1 mutations
      was investigated by amplification refractory mutation system (ARMS) PCR and by
      Sanger sequencing. NOTCH1 mutations occurred in 20 out of 123 (16.3 %) cases.
      Consolidated patients showed longer OS than unconsolidated patients (p = 0.030).
      Both NOTCH1 mutated and CR MRD+ or PR NOTCH1 mutated patients showed
      significantly shorter OS after treatment (p = 0.00014 and p = 0.0021,
      respectively). Moreover, NOTCH1 wild-type consolidated cases experienced
      significantly longer RD and OS than NOTCH1 mutated consolidated or not
      consolidated cases (p = 0.00001 and p = 0.018, respectively). Finally, the
      independent prognostic impact of NOTCH1 mutations for OS was confirmed in
      multivariate analysis (p < 0.001). The presence of NOTCH1 mutations identifies a
      CLL subset with worse prognosis in the setting of a rituximab-based induction and
      consolidation treatment.

PMID- 24923452
TI  - Unusual relapse of an angioimmunoblastic T cell lymphoma 11 years after initial
      manifestation.

PMID- 24923453
TI  - Conversion from nuclear bilobation to indentation in BCR/ABL1-positive acute
      myeloid leukemia lacking CD34 and HLA-DR expression.

PMID- 24923454
TI  - Effectiveness of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP)
      combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T
      cell lymphoma: a retrospective study of 17 patients.
AB  - The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal
      because of its aggressive course and multidrug resistance. Currently, for
      patients with relapsed/refractory ENKL, L-asparaginase-based regimens such as L
      asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or L
      asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We
      retrospectively investigated the efficacy and safety of gemcitabine,
      pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the
      treatment of 17 relapsed/refractory ENKL patients. Clinical data from these
      patients were collected and analyzed. The primary end point was overall response
      rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy,
      and the median number of cycles of DDGP regimen administrated was four. The ORR
      was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR)
      and six patients (35.3 %) achieved partial response (PR). The median follow-up
      time was 17 months (range 2-28 months). The 1-year overall survival (OS) rate and
      1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For
      those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred
      in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients
      (35.3 %). DDGP combination chemotherapy produces favorable outcomes in
      relapsed/refractory ENKL, and more attention should be paid to treatment-related
      myelosuppression. Further prospective trials are expected to define the efficacy.

PMID- 24923455
TI  - Cetuximab in metastatic squamous cell cancer of the skin: a Swiss case series.
AB  - BACKGROUND: There is current evidence that non-melanoma skin cancers can be
      successfully treated with cetuximab. OBJECTIVE: To evaluate the use and efficacy
      of cetuximab (with or without radiotherapy) in a series of previously treated
      patients with metastatic squamous cell cancer of the skin (SCCS) in Switzerland.
      METHODS: We performed a retrospective analysis of six patients from four centers.
      Endpoints were disease control rates (DCRs) at 4-8 weeks, 12-14 weeks and 20-36
      weeks of treatment. Treatment-related toxicity was evaluated additionally.
      RESULTS: A median of 14 cycles of cetuximab were applied. DCR was 67% at 4-8
      weeks, 50% at 12-14 weeks and 33% at 20-36 weeks. In 4-8 weeks responders, mean
      relapse-free time was 12 +/- 6.2 months and mean overall survival was 25 +/- 16.2
      months. Grade I-III acne-like rash developed around week 3 of treatment in 83%.
      CONCLUSIONS: Cetuximab treatment in patients with metastatic SCCS achieved an
      overall DCR of 67% at 4-8 weeks of treatment. This study underlines the current
      evidence that SCCS can be successfully treated with cetuximab.

PMID- 24923456
TI  - Blood-based biomarkers in depression: emerging themes in clinical research.
AB  - There is growing interest in identifying blood-based biomarkers for depression.
      This brief review examines recent research in this area, using a focused
      literature search to identify emerging themes in current work pertaining to major
      depressive disorder (MDD). The results suggest that biomarker-based research in
      MDD is still in its relative infancy and is focused on answering two major
      questions: what biomarkers reliably distinguish individuals with MDD from those
      without MDD; and what biomarkers can identify or predict treatment responders
      versus non-responders? However, a number of issues limit the potential utility of
      positive findings in each case; chief among these is the lack of truly
      independent replication cohorts in which to validate initial findings. Some
      promising results have emerged pertaining to predictors of antidepressant
      effectiveness and, if validated by future independent studies, these may hold
      promise as targets to be developed within clinical settings and may ultimately
      guide treatment regimens for patients suffering from MDD. 

PMID- 24923457
TI  - Bringing epigenetics into the diagnostics of the andrology laboratory: challenges
      and perspectives.
AB  - Recent studies have shown significant associations of aberrant DNA methylation in
      spermatozoa with idiopathic male infertility, increased frequency of spontaneous
      abortions and imprinting disorders. Thus, the analysis of DNA methylation of
      specific genes in spermatozoa has the potential to become a new valuable
      diagnostic marker in clinical andrology. This perspective article discusses the
      current state and value of DNA methylation analysis in the diagnostic setup of
      infertile men and outlines challenges and perspectives. It highlights the
      potential of DNA methylation in andrological diagnostics and its putative benefit
      in the examination of hitherto idiopathic infertile patients is described.

PMID- 24923458
TI  - Novel methylation specific real-time PCR test for the diagnosis of Klinefelter
      syndrome.
AB  - The aim of this study was to design a molecular assay for the diagnosis of
      Klinefelter syndrome (KS), based on the detection of supernumerary X-chromosomes
      (X-chs). DNA was extracted from peripheral blood samples of twenty-six 47,XXY
      males; two 46,XY/47,XXY males; twenty-two 46,XY males; and 15 females; and
      deaminated. Methylation-specific quantitative polymerase chain reaction (MS-qPCR)
      was performed using primers for unmethylated and methylated copies of the X-ch
      inactive-specific transcript (XIST-U and XIST-M) gene. X-ch disomy was determined
      on the basis of XIST methylation status. Degree of mosaicism in the 46,XY/47,XXY
      males was compared with karyotype and fluorescent in situ hybridization (FISH)
      results. Data analysis was performed using the Roche(r) LightCycler software V.
      3.5.3., including determination of crossing points (CPs) by fit-point analysis
      and melting curve analysis. X-ch disomy was detected in all female controls and
      KS patients; male controls expressed XIST-M only. CPs ranged from 29.5 to 32.5
      (standard deviation (s.d.) 0.8) for XIST-U and from 29 to 31 (s.d. 0.6) for XIST
      M. Limit of detection of mosaicism was 1%. Based on XIST-U/XIST-M ratios for the
      two 47,XXY/46,XY patients, the calculated degree of mosaicism (1.8% and 17.8%)
      was comparable to FISH results (2.3% and 15%, respectively). Turnaround time from
      DNA deamination to final data analysis was under 9 h. We conclude that MS-qPCR is
      a sensitive, specific and rapid test for the detection of X-ch disomy, with
      applicability for the screening and diagnosis of KS, even in the setting of low
      grade 47,XXY/46,XY mosaicism.

PMID- 24923459
TI  - Physiological normal levels of androgen inhibit proliferation of prostate cancer
      cells in vitro.
AB  - For more than 70 years, it has been believed that a severe reduction of serum
      androgen levels caused regression of prostate cancer (PCa) and that increasing
      androgen levels enhanced growth of PCa. However, numerous recent studies have
      questioned this traditional belief. In our study, LNCaP and MDA PCa 2b PCa cells
      were treated with various levels of androgens for 10 or 20 days, and the cell
      growth was measured with crystal violet mitogenic assay. The results indicated
      that the effect of androgens on the proliferation of PCa cells occurs in a
      biphasic pattern, with the androgen levels promoting optimal cell growth at
      approximately 0.23 ng ml-1 for LNCaP cells and between 1 and 2 ng ml-1 for MDA
      PCa 2b cells. Both of the optimal androgen levels are within the adult men's
      physiological low range (<2.4 ng ml-1). At lower concentrations than the optimal
      androgen level, increasing androgen concentration promoted the proliferation of
      PCa cells. However, at the higher concentrations, increasing androgen
      concentration resulted in a dose-dependent proliferative inhibition. We conclude
      that physiologically normal levels of androgen inhibit the proliferation of PCa
      cells in vitro. However, at very low levels androgens are essential for initial
      growth of PCa cells.

PMID- 24923460
TI  - Expression of the SET protein in testes of mice at different developmental
      stages.
AB  - SET is a multifunctional protein involved in regulating many biological processes
      of the cell cycle. It is also a regulator of steroidogenesis in the ovary.
      However, the expression of SET protein in testis, and its function, still remains
      ambiguous. In this study, we observed the expression of SET in the testes of mice
      at different developmental stages, and have discussed its potential function in
      regulating spermatogenesis and androgen production. Forty-eight male mice at
      different developmental stages (1 week old as the infancy group; 4 weeks old as
      the prepubertal group; 12 weeks old as the adult group; over 12 months old as the
      ageing group) were used. Cellular location of SET protein in the testes was
      observed by immuno-histochemistry. Expression levels of Set mRNA and SET protein
      were analyzed by quantitative polymerase chain reaction and Western blotting. SET
      protein was expressed in spermatogonial cells and spermatocytes; the highest
      level was mainly in haploid and tetraploid cells of the prepubertal and adult
      groups, and Leydig cells of the adult and ageing groups. There was a low
      expression in Sertoli cells. Expression of Set mRNA in the prepubertal group was
      significantly higher than that in the adult group (P < 0.05), while expression of
      SET protein was at the highest level in the adult group (P < 0.05). SET protein
      is mainly expressed in spermatogonial cells and spermatocytes, and poorly
      expressed in Sertoli cells, suggesting that it is involved in spermatogenesis.
      Expression of SET protein in Leydig cells suggests a possible role in
      steroidogenesis.

PMID- 24923461
TI  - Body mass index and acute coronary syndromes: paradox or confusion?
AB  - BACKGROUND: A better prognosis in obese patients has been described in acute
      coronary syndromes (ACS). However, this evidence is mostly based on retrospective
      studies and has provided conflicting results. No study reported cause-specific
      mortality according to body mass index (BMI) in ACS. We aimed to prospectively
      assess the impact of BMI on mortality and its specific causes in ACS patients.
      METHODS: We included non-selected ACS patients admitted in a tertiary care
      coronary unit, collecting baseline characteristics, management and clinical
      course. Patients were stratified into five clinically meaningful BMI subgroups of
      <20, 20-24.9, 25-29.9, 30-35, >35 kg/m(2). The primary outcome was 1 year
      mortality, its causes and its association with BMI. This association was assessed
      by the Cox regression method. RESULTS: We included 2040 patients in our study
      with a mean age of 62.1 years. Low weight patients (BMI <20) were older, with
      less cardiovascular risk factors, higher prevalence of chronic obstructive
      pulmonary disease and worse renal function. Mean follow up was 334 days. The
      unadjusted analysis showed lower all-cause mortality in all subgroups as compared
      to low weight patients. After adjusting for potential confounders, this
      association remained significant for patients with a BMI 20-24.9. Cardiac
      mortality was similar across BMI subgroups. In contrast, the adjusted analysis
      showed a significantly lower non-cardiac mortality in patients with a BMI 20
      24.9, 25-29.9 and 30-35 as compared to low weight patients. CONCLUSIONS: Baseline
      characteristics in ACS patients significantly differ according to their BMI
      status. The prognostic impact of BMI seems mostly related to extra-cardiac causes
      in low weight patients.

PMID- 24923463
TI  - Revision of the Osteoporosis Knowledge Test: Reliability and Validity.
AB  - The purpose of this study was to revise the Osteoporosis Knowledge Test (OKT) and
      evaluate its reliability and validity. The original OKT, developed in the early
      1990 s, needed updating based on current research. A convenience sample of 105
      adults completed the draft revised OKT. A subsample (n = 27) completed the
      questionnaire 2 weeks later to determine stability. The sample was recruited from
      diverse sites in western and northern Michigan over a year. The 32-item Revised
      OKT (2012) demonstrated internal consistency (total scale Kuder-Richardson-20 =
      .85, Nutrition subscale = .83, and Exercise subscale = .81). Test-retest analysis
      resulted in a Pearson correlation coefficient of .87. Validity was evaluated by
      content validity. Questions were examined for difficulty, effectiveness of
      distracters, and discrimination. In addition, measures of point-biserial,
      internal consistency and stability were determined. The Revised OKT (2012) is a
      comprehensive instrument reflecting current research and assesses osteoporosis
      knowledge of adults.

PMID- 24923464
TI  - Neuroprotective effects of metallothionein against rotenone-induced myenteric
      neurodegeneration in parkinsonian mice.
AB  - Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as
      well as non-motor symptoms that precede the onset of motor symptoms.
      Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD
      pathology in the central nervous system (CNS) and enteric nervous system (ENS).
      We reported previously that metallothioneins (MTs) released from astrocytes can
      protect dopaminergic neurons against oxidative stress. The present study examined
      the changes in MT expression by chronic systemic rotenone administration in the
      striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated
      the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS
      using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from
      MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6
      weeks caused neurodegeneration, increased MT expression with astrocytes
      activation in the striatum and myenteric plexus. MT KO mice showed more severe
      myenteric neuronal damage by rotenone administration after 4 weeks than wild-type
      mice, accompanied by reduced astroglial activation. In primary cultured
      mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in
      dopaminergic neurons, which was complemented by addition of recombinant protein.
      The present results suggest that MT seems to provide protection against
      neurodegeneration in ENS of rotenone-induced PD model mice.

PMID- 24923465
TI  - High-frequency hearing thresholds: effects of age, occupational ultrasound and
      noise exposure.
AB  - PURPOSE: It has been suggested that high-frequency audiometry (HFA) could
      represent a useful preventive measure in exposed workers. The aim was to
      investigate the effects of age, ultrasound and noise on high-frequency hearing
      thresholds. METHODS: We tested 24 industrial ultrasound-exposed subjects, 113
      industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was
      tested with both conventional-frequency (0.125-8 kHz) and high-frequency (9-18
      kHz) audiometry. RESULTS: The hearing threshold at high frequency deteriorated as
      a function of age, especially in subjects more than 30 years old. The ultrasound
      exposed subjects had significantly higher hearing thresholds than the non-exposed
      ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss
      was already significantly evident in subjects with exposure <5 years and
      increased with years of exposure and advancing age. The noise exposure group had
      significantly higher hearing thresholds than the non-exposed group at the
      conventional frequencies 4 and 6 kHz and at the high frequency of 14 kHz. After
      stratification for age, there was a significant difference between the two groups
      at 9-10 and 14-15 kHz only for those under 30 years of age. CONCLUSION:
      Multivariate analysis indicated that age was the primary predictor, and noise and
      ultrasound exposure the secondary predictors of hearing thresholds in the high
      frequency range. The results suggest that HFA could be useful in the early
      diagnosis of noise-induced hearing loss in younger groups of workers (under 30
      years of age).

PMID- 24923466
TI  - Ca2+ influx through P2X1 receptors amplifies P2Y1 receptor-evoked Ca2+ signaling
      and ADP-evoked platelet aggregation.
AB  - Many cells express both P2X cation channels and P2Y G-protein-coupled receptors
      that are costimulated by nucleotides released during physiologic or
      pathophysiologic responses. For example, during hemostasis and thrombosis, ATP
      gated P2X1 channels and ADP-stimulated P2Y1 and P2Y12 G-protein coupled receptors
      play important roles in platelet activation. It has previously been reported that
      P2X1 receptors amplify P2Y1-evoked Ca(2+) responses in platelets, but the
      underlying mechanism and influence on function is unknown. In human platelets, we
      show that maximally activated P2X1 receptors failed to stimulate significant
      aggregation but could amplify the aggregation response to a submaximal
      concentration of ADP. Costimulation of P2X1 and P2Y1 receptors generated a
      superadditive Ca(2+) increase in both human platelets and human embryonic kidney
      293 (HEK293) cells via a mechanism dependent on Ca(2+) influx rather than Na(+)
      influx or membrane depolarization. The potentiation, due to an enhanced P2Y1
      response, was observed if ADP was added up to 60 seconds after P2X1 activation.
      P2X1 receptors also enhanced Ca(2+) responses when costimulated with type 1
      protease activated and M1 muscarinic acetylcholine receptors. The P2X1-dependent
      amplification of Gq-coupled [Ca(2+)]i increase was mimicked by ionomycin and was
      not affected by inhibition of protein kinase C, Rho-kinase, or extracellular
      signal-regulated protein kinase 1/2, which suggests that it results from
      potentiation of inositol 1,4,5-trisphosphate receptors and/or phospholipase C. We
      conclude that Ca(2+) influx through P2X1 receptors amplifies Ca(2+) signaling
      through P2Y1 and other Gq-coupled receptors. This represents a general form of co
      incidence detection of ATP and coreleased agonists, such as ADP at sites of
      vascular injury or synaptic transmitters acting at metabotropic Gq-coupled
      receptors.

PMID- 24923467
TI  - Problems of in vitro SPF measurements brought about by viscous fingering
      generated during sunscreen applications.
AB  - Up to date, no worldwide standard in vitro method has been established for the
      determination of the sun protection factor (SPF), since there are many problems
      in terms of its repeatability and reliability. Here, we have studied the problems
      on the in vitro SPF measurements brought about by the phenomenon called viscous
      fingering. A spatially periodic stripe pattern is usually formed spontaneously
      when a viscous fluid is applied onto a solid substrate. For the in vitro SPF
      measurements, the recommended amount of sunscreen is applied onto a substrate,
      and the intensity of the transmitted UV light through the sunscreen layer is
      evaluated. Our theoretical analysis indicated that the nonuniformity of the
      thickness of the sunscreen layer varied the net UV absorbance. Pseudo-sunscreen
      composites having no phase separation structures were prepared and applied on a
      quartz plate for the measurements of the UV absorbance. Two types of applicators,
      a block applicator and a 4-sided applicator were used. The flat surface was
      always obtained when the 4-sided applicator was used, while the spatially
      periodic stripe pattern was always generated spontaneously when the block
      applicator was used. The net UV absorbance of the layer on which the stripe
      pattern was formed was found to be lower than that of the flat layer having the
      same average thickness. Theoretical simulations quantitatively reproduced the
      variation of the net UV absorbance led by the change of the geometry of the
      layer. The results of this study propose the definite necessity of strict
      regulations on the coating method of sunscreens for the establishment of the in
      vitro SPF test method.

PMID- 24923468
TI  - AuPd/polyaniline as the anode in an ethylene glycol microfluidic fuel cell
      operated at room temperature.
AB  - AuPd/polyaniline was used for the first time, for ethylene glycol (EG)
      electrooxidation in a novel microfluidic fuel cell (MFC) operated at room
      temperature. The device exhibits high electrocatalytic performance and stability
      for the conversion of cheap and fully available EG as fuel. 

PMID- 24923469
TI  - Standard operating procedures for antibiotic therapy and the occurrence of acute
      kidney injury: a prospective, clinical, non-interventional, observational study.
AB  - INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of
      Intensive Care Unit (ICU) patients. It increases mortality, hospital length of
      stay, and costs. The aim of this study was to investigate, whether there is an
      association between adherence to guidelines (standard operating procedures (SOP))
      for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This
      study was carried out as a prospective, clinical, non-interventional,
      observational study. Data collection was performed over a total of 170 days in
      three ICUs at Charite - Universitaetsmedizin Berlin. A total of 675 patients were
      included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin;
      were >18 years; and treated in the ICU for >24 hours. Patients with an adherence
      to SOP >70% were classified into the high adherence group (HAG) and patients with
      an adherence of <70% into the low adherence group (LAG). AKI was defined
      according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective
      expert audit. Development of AKI was compared between groups with exact Chi2-test
      and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG
      consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred
      significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic
      characteristics were comparable, except an increased rate of soft tissue
      infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for
      LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P =
      0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics
      was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN54598675. Registered 17 August 2007.

PMID- 24923470
TI  - Spatial distribution of mercury and arsenic levels in water, soil and cassava
      plants in a community with long history of gold mining in Tanzania.
AB  - This study examined the spatial distribution of total mercury (THg) and total
      arsenic (TAs) in water, soil and cassava (Manihot esculenta) (leaves and roots)
      samples taken from areas in Rwamagasa village in northwestern Tanzania where
      daily living activities occur in close proximity to extensive artisanal and small
      scale gold mining. Results indicated that 33.3 % of the water sources had THg
      levels above the WHO guideline of 1.0 ug/L for safe drinking water, and 12.5 %
      had TAs levels above 10 ug/L. Cassava leaves were found to have higher THg
      (ranging from 8.3 to 167 ug/kg) and TAs (ranging from 60 to 1,120 ug/kg) levels
      than cassava roots, which ranged between 1.2-8.3 ug/kg for THg and 25-310 ug/kg
      for TAs. Concentrations of THg and TAs in soil samples ranged between 5.8-1,759
      and 183-20,298 ug/kg, respectively. Both THg and TAs were found to be distributed
      throughout Rwamagasa village.

PMID- 24923471
TI  - Mimicking biological membranes with programmable glycan ligands self-assembled
      from amphiphilic Janus glycodendrimers.
AB  - An accelerated modular synthesis produced 18 amphiphilic Janus glycodendrimers
      with three different topologies formed from either two or one carbohydrate head
      groups or a mixed constellation with a noncarbohydrate hydrophilic arm. By simple
      injection of their THF solutions into water or buffer, all of the Janus compounds
      self-assembled into uniform, stable, and soft unilamellar vesicles, denoted
      glycodendrimersomes. The mixed constellation topology glycodendrimersomes were
      demonstrated to be most efficient in binding plant, bacterial, and human lectins.
      This evidence with biomedically relevant receptors offers a promising perspective
      for the application of such glycodendrimersomes in targeted drug delivery,
      vaccines, and other areas of nanomedicine. 

PMID- 24923472
TI  - Multiparameter MRI analysis of the time course of induced muscle damage and
      regeneration.
AB  - PURPOSE: To test the ability of different magnetic resonance imaging (MRI)
      modalities to discriminate the time course of damage and regeneration in a model
      of acute, toxin-induced muscle damage. MATERIALS AND METHODS: We analyzed the
      time course of tissue and cellular changes in mouse lower limb musculature
      following localized injection of myotoxin by T2 , magnetization transfer (MT),
      and diffusion-weighted MRI. We also used T1 -weighted imaging to measure leg
      muscle volume. In addition, postmortem histological analysis of toxin-injected
      muscles was compared to uninjected controls. RESULTS: The damages detected by the
      MRI modalities are transient and recover within 3 weeks. Muscle water diffusivity
      and edema measured by leg volume increased within the first hours after injection
      of the toxin. The rate constant for volume increase was 0.65 +/- 0.11 hr(-1) ,
      larger than the increase in T2 (0.045 +/- 0.013 hr(-1) ) and change in MT ratio
      (0.028 +/- 0.021 hr(-1) ). During repair phase, the rate constants were much
      smaller: 0.022 +/- 0.004 hr(-1) , 0.013 +/- 0.0019 hr(-1) and 0.0042 +/- 0.0016
      hr(-1) for volume, T2 , and MT ratio, respectively. Histological analyses
      confirmed the underlying cellular changes that matched the progression of MR
      images. CONCLUSION: The kinetics of change in the MRI measurements during the
      progression of damage and repair shows MRI modalities can be used to distinguish
      these processes.

PMID- 24923473
TI  - OpenIGTLink interface for state control and visualisation of a robot for image
      guided therapy systems.
AB  - PURPOSE: The integration of a robot into an image-guided therapy system is still
      a time consuming process, due to the lack of a well-accepted standard for
      interdevice communication. The aim of this project is to simplify this procedure
      by developing an open interface based on three interface classes: state control,
      visualisation, and sensor. A state machine on the robot control is added to the
      concept because the robot has its own workflow during surgical procedures, which
      differs from the workflow of the surgeon. METHODS: A KUKA Light Weight Robot is
      integrated into the medical technology environment of the Institute of
      Mechatronic Systems as a proof of concept. Therefore, 3D Slicer was used as
      visualisation and state control software. For the network communication the
      OpenIGTLink protocol was implemented. In order to achieve high rate control of
      the robot the "KUKA Sunrise. Connectivity SmartServo" package was used. An
      exemplary state machine providing states typically used by image-guided therapy
      interventions, was implemented. Two interface classes, which allow for a direct
      use of OpenIGTLink for robot control on the one hand and visualisation on the
      other hand were developed. Additionally, a 3D Slicer module was written to
      operate the state control. RESULTS: Utilising the described software concept the
      state machine could be operated by the 3D Slicer module with 20 Hz cycle rate and
      no data loss was detected during a test phase of approximately 270s (13,640
      packages). Furthermore, the current robot pose could be sent with more than 60
      Hz. No influence on the performance of the state machine by the communication
      thread could be measured. CONCLUSION: Simplified integration was achieved by
      using only one programming context for the implementation of the state machine,
      the interfaces, and the robot control. Eventually, the exemplary state machine
      can be easily expanded by adding new states.

PMID- 24923474
TI  - Statistical atlas-based morphological variation analysis of the asian humerus:
      towards consistent allometric implant positioning.
AB  - PURPOSE: Positioning existing humeral implants into Asian patients poses
      significant challenges due to the inconsistent statistical shapes between Western
      population and Asian population. Current humeral orthopedic fixation devices and
      implants have a generic shape and are not designed for Asian patients who exhibit
      different sizes and shapes compared to their Western counterparts for which
      present day designs have been based on. To address this problem, it is necessary
      to develop Asian-specific implants that accommodate the morphology of Asian
      humeri. Existing morphological studies of humeri in Asian populations are rare
      and most previous analyses are either based on the manual measurement of dry
      bones or the use of dual energy X-ray absorptiometry scans. The purpose of this
      pilot morphological study is to explore the characteristics of Asian humeri using
      statistical atlas-based analysis. METHODS: Forty-four CT scans of normal upper
      limbs were obtained from the National University Hospital, Singapore and used to
      construct statistical humerus atlases. The atlases were subsequently used to
      study the morphology of the humeri in an Asian population. Humeral shapes of
      different patient clusters were analyzed based on statistical shape models.
      Comparison between different clusters was conducted with regard to centerline,
      length, width and surface curvature. RESULTS: The statistical humerus atlases
      reflected the mean shape and modes of variation of humeri in an Asian population.
      Analyses based on these atlases indicated that curvature and shape of the
      internal humeral canal were similar in males and females while humeral length and
      width were greater in males. Most importantly, surface curvatures were explicitly
      different between clusters. CONCLUSION: Morphologic analysis based on statistical
      atlases is novel and useful to characterize the Asian humerus. The humerus
      demonstrates gender-specific morphology. This unique approach provides
      information that is useful to the clinician and biomedical engineer, not only in
      the modification of current or design of future humeral implants, but also in the
      precise dynamic positioning of Asian-specific humeral implants to Asian patients.
      Our findings support the need for further development of humeral implants,
      curvilinear robotics, and the questioning of whether gender-specific devices are
      necessary.

PMID- 24923475
TI  - Tumor induction in mice after local irradiation with single doses of either
      carbon-ion beams or gamma rays.
AB  - PURPOSE: To determine the dose-dependent relative biological effectiveness (RBE)
      for tumor prevalence in mice receiving single localized doses to their right leg
      of either carbon ions (15, 45 or 75 keV/MUm) or 137Cs gamma rays. METHODS AND
      MATERIALS: A total of 1647 female C3H mice were irradiated to their hind legs
      with a localized dose of either reference gamma rays or 15, 45 or 75 keV/MUm
      carbon-ion beams. Irradiated mice were evaluated for tumors twice a month during
      their three-year life span, and the dimensions of any tumors found were measured
      with a caliper. The tumor induction frequency was calculated by Kaplan-Meier
      analysis. RESULTS: The incidence of tumors from 50 Gy of 45 keV/MUm carbon ions
      was marginally higher than those from 50 Gy of gamma rays. However, 60 Gy of 15
      keV/MUm carbon ions induced significantly fewer tumors than did gamma rays. RBE
      values of 0.87 + 0.12, 1.29 + 0.08 or 2.06 + 0.39 for lifetime tumorigenesis were
      calculated for 15, 45 or 75 keV/MUm carbon-ion beams, respectively. Fibrosarcoma
      predominated, with no Linear Energy Transfer (LET)-dependent differences in the
      tumor histology. Experiments measuring the late effect of leg skin shrinkage
      suggested that the carcinogenic damage of 15 keV/MUm carbon ions would be less
      than that of gamma rays. CONCLUSIONS: We conclude that patients receiving
      radiation doses to their normal tissues would face less risk of secondary tumor
      induction by carbon ions of intermediate LET values compared to equivalent doses
      of photons.

PMID- 24923477
TI  - Gadoxetate disodium in patients with primary sclerosing cholangitis: an analysis
      of hepatobiliary contrast excretion.
AB  - PURPOSE: To assess hepatobiliary excretion of gadoxetate disodium in patients
      with primary sclerosing cholangitis (PSC) over time and to determine a possible
      correlation with severity of the disease. MATERIALS AND METHODS: A total of 111
      patients (36 females, 75 males, mean age 41.5 yr) with confirmed diagnosis of PSC
      who underwent gadoxetate disodium enhanced hepatic MRI were included in this
      retrospective institutional review board-approved study. Hepatocyte phase images
      (10-493 min post injection [p.i.]) were evaluated by one radiologist for the
      presence of contrast agent in the intrahepatic bile ducts (IBD), common bile duct
      (CBD), gallbladder (GB), and duodenum. In 54 patients, in whom hepatocyte phase
      scans were acquired within 10-20 min p.i., hepatobiliary excretion was compared
      with data collected in a previous study from patients without liver disease
      (controls; Mann-Whitney U-test). Excretion was further correlated with liver
      function tests (Kruskal-Wallis test). RESULTS: Compared with controls, excretion
      was significantly delayed in patients with PSC: 20 min p.i. gadoxetate disodium
      could be detected in the IBD in 55.6% (controls:100%), CBD 53.7% (controls:100%),
      GB 39.6% (controls:87%), duodenum 13% (controls:66%), respectively. Contrast
      appearance in different bile duct sections increased over time and correlated
      significantly with serum bilirubin and AP levels (P < 0.05). CONCLUSION:
      Hepatobiliary excretion of gadoxetate disodium in PSC patients is significantly
      delayed. Excretion correlates with bilirubin levels, and thus indirectly with
      severity of disease.

PMID- 24923476
TI  - DCE-MRI of the liver: effect of linear and nonlinear conversions on hepatic
      perfusion quantification and reproducibility.
AB  - PURPOSE: To evaluate the effect of different methods to convert magnetic
      resonance (MR) signal intensity (SI) to gadolinium concentration ([Gd]) on
      estimation and reproducibility of model-free and modeled hepatic perfusion
      parameters measured with dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND
      METHODS: In this Institutional Review Board (IRB)-approved prospective study, 23
      DCE-MRI examinations of the liver were performed on 17 patients. SI was converted
      to [Gd] using linearity vs. nonlinearity assumptions (using spoiled gradient
      recalled echo [SPGR] signal equations). The [Gd] vs. time curves were analyzed
      using model-free parameters and a dual-input single compartment model. Perfusion
      parameters obtained with the two conversion methods were compared using paired
      Wilcoxon test. Test-retest and interobserver reproducibility of perfusion
      parameters were assessed in six patients. RESULTS: There were significant
      differences between the two conversion methods for the following parameters:
      AUC60 (area under the curve at 60 s, P < 0.001), peak gadolinium concentration
      (Cpeak, P < 0.001), upslope (P < 0.001), Fp (portal flow, P = 0.04), total
      hepatic flow (Ft, P = 0.007), and MTT (mean transit time, P < 0.001). Our
      preliminary results showed acceptable to good reproducibility for all model-free
      parameters for both methods (mean coefficient of variation [CV] range, 11.87
      23.7%), except for upslope (CV = 37%). Among modeled parameters, DV (distribution
      volume) had CV <22% with both methods, PV and MTT showed CV <21% and <29% using
      SPGR equations, respectively. Other modeled parameters had CV >30% with both
      methods. CONCLUSION: Linearity assumption is acceptable for quantification of
      model-free hepatic perfusion parameters while the use of SPGR equations and T1
      mapping may be recommended for the quantification of modeled hepatic perfusion
      parameters.

PMID- 24923478
TI  - Cardiovascular magnetic resonance validation of fractional changes in annulo
      apical angles and tricuspid annular plane systolic excursion for rapid assessment
      of right ventricular systolic function.
AB  - PURPOSE: To evaluate the use of right ventricular (RV) annulo-apical angle (AA)
      changes acquired by magnetic resonance imaging (MRI), alongside tricuspid annular
      plane systolic excursion (TAPSE), for its association with RV systolic function.
      MATERIALS AND METHODS: Thirty patients with varying RV dysfunction and 10 normal
      controls were enrolled and scanned after obtaining written consent. Systolic
      change in AAs, alpha (alpha), beta (beta), and theta (theta), subtended by a
      triangle connecting the septal and lateral extent of the tricuspid valve annulus
      and RV apex, and TAPSE were measured. Spearman rank correlations of parameters
      with RV ejection fraction (RVEF) were performed. Receiver operating
      characteristic (ROC) analysis was used to determine accuracy of these surrogate
      markers for detecting abnormal RVEF. RESULTS: Correlations with RVEF included:
      TAPSE (r = 0.74 P < 0.001), fractional systolic changes in alpha angle (0.64, P <
      0.001), beta angle (-0.39, P < 0.05), and theta angle (-0.77, P < 0.001). The
      best markers for RVEF <50% were fractional theta angle change >= -25.5% (eg, 
      24%) (sensitivity of 97% and specificity of 91%), and TAPSE <=1.87 cm
      (sensitivity of 100% and specificity of 82%). Intra- and inter-observer agreement
      was excellent, with intraclass correlation coefficients for fractional theta
      angle change (intra = 0.96, inter = 0.94) and TAPSE (intra = 0.98, inter = 0.87).
      CONCLUSION: Fractional theta angle change is a useful semiquantitative parameter
      associated with the presence and severity of RV systolic dysfunction, with high
      observer agreement.

PMID- 24923479
TI  - MRI appearances of ovarian serous borderline tumor: pathological correlation.
AB  - PURPOSE: To investigate the spectrum of MRI appearances of ovarian serous
      borderline tumor (SBT). MATERIALS AND METHODS: Following ethics approval, 31
      patients with 51 histologically proven ovarian SBTs underwent preoperative MRI.
      Images were evaluated, by two observers for the location, shape, size, internal
      architecture, signal intensity, and extent or stage of the tumors. The MRI
      findings were correlated with pathological findings. RESULTS: Twenty of 31
      patients (65%) demonstrated bilateral ovarian SBTs on MRI. Three MRI
      morphological patterns of ovarian SBT were identified: (i) Mainly cystic mass
      with multiple intracystic papillary projections from the wall and septations was
      observed in 24 (47%) tumors. (ii) Solid mass with hierarchical branching
      papillary and fibrous stalk architecture was observed in 8 (16%) tumors. The
      branching papillary projections were hyperintensity on T2WI, intermediate intense
      on DWI, and enhanced intensely after the administration of Gd-DTPA. The internal
      branching fibrous stalks were hypointensity on T2WI and enhanced slightly. (iii)
      Mixed cystic-solid mass was observed in 19 (37%) tumors. The cystic and solid
      components had the architecture and signal intensity similar to those of cystic
      and solid SBTs. Papillary projections were the common architecture of all three
      types of tumors. CONCLUSION: On MRI, the ovarian SBT has some morphological
      distinguishing features. The solid papillary architecture with internal branching
      fibrous stalk is a somewhat more characteristic MRI appearance.

PMID- 24923480
TI  - Accuracy of diffusion-weighted (DW) MRI with background signal suppression (MR
      DWIBS) in diagnosis of mediastinal lymph node metastasis of nonsmall-cell lung
      cancer (NSCLC).
AB  - PURPOSE: To prospectively evaluate the accuracy of diffusion-weighted (DW)
      magnetic resonance (MR) imaging with background signal suppression (MR-DWIBS) for
      detecting mediastinal lymph node metastasis of nonsmall-cell lung cancer (NSCLC).
      MATERIALS AND METHODS: MR-DWIBS was performed in 42 consecutive patients (27 men,
      15 women; age range, 42-78 years; median age, 55 years) with histologically
      proven NSCLC. The visualization rate of metastatic lymph node (MLN) and benign
      lymph node (BLN) of enlarged lymph nodes (ELN) and normal-sized lymph nodes (NLN)
      was compared by using a chi-square test or Fisher's exact test on a per-nodal
      basis. Apparent diffusion coefficient (ADC) of MLN and BLN was measured and
      compared by using two-tailed unpaired Student's t-test. Receiver operating
      characteristic (ROC) analysis was used to assess the overall diagnostic accuracy
      of ADC for ELN and NLN. The optimal cutoff value was determined and the
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy was calculated. RESULTS: Thirty-five out of 119 lymph
      resected nodes were confirmed to be metastatic by histologic examination. The
      visualization rate of MLN was significantly higher than that of BLN for ELN (P <
      0.001) and for NLN (chi(2) = 7.506, P = 0.006). For both ELN and NLN, ADC of MLN
      was significantly lower than that of BLN (t = -5.380, P < 0.001 and t = -6.435, P
      < 0.001). ADC was significant for detection of MLN for both ELN (Az = 0.975, P <
      0.001) and NLN (Az = 0.919, P < 0.001). For NLN, the optimal cutoff value of ADC
      was 2.04 mm(2)/s, where the sensitivity, specificity, PPV, NPV, and accuracy were
      75.0%, 90.9%, 66.7%, 93.8%, and 87.8%, respectively. CONCLUSION: MR-DWIBS may be
      clinically useful to visually detect mediastinal lymph nodes and ADC measurement
      can aid in malignant node discrimination.

PMID- 24923482
TI  - Isolation and purification of diastereoisomeric flavonolignans from silymarin by
      binary-column recycling preparative high-performance liquid chromatography.
AB  - Silymarin extracted from Silybum marianum (L.) Gaertn consists of a large number
      of flavonolignans, of which diastereoisomeric flavonolignans including silybin A
      and silybin B, and isosilybin A and isosilybin B are the main bioactive
      components, whose preparation from the crude extracts is still a difficult task.
      In this work, binary-column recycling preparative high-performance liquid
      chromatography systems without sample loop trapping, where two columns were
      switched alternately via one or two six-port switching valves, were established
      and successfully applied to the isolation and purification of the four
      diastereoisomeric flavonolignans from silymarin. The proposed system showed
      significant advantages over conventional preparative high-performance liquid
      chromatography with a single column in increasing efficiency and reducing the
      cost. To obtain the same amounts of products, the proposed system spends only one
      tenth of the time that the conventional system spends, and needs only one
      eleventh of the solvent that the conventional system consumes. Using the proposed
      system, the four diastereoisomers were successfully isolated from silymarin with
      purities over 98%. 

PMID- 24923483
TI  - High-efficiency orange and tandem white organic light-emitting diodes using
      phosphorescent dyes with horizontally oriented emitting dipoles.
AB  - Tandem white organic light-emitting diodes (WOLEDs) using horizontally oriented
      phosphorescent dyes in an exciplex-forming co-host are presented, along with an
      orange OLED. A high external quantum efficiency of 32% is achieved for the orange
      OLED at 1000 cd m(-2) and the tandem WOLEDs exhibit a high maximum EQE of 54.3%
      (PE of 63 lm W(-1)).

PMID- 24923481
TI  - Measurement of apparent diffusion coefficient with simultaneous MR/positron
      emission tomography in patients with peritoneal carcinomatosis: comparison with
      18F-FDG-PET.
AB  - PURPOSE: To characterize peritoneal carcinomatosis (PC) of different
      histologically proven primary tumors based on diffusion-weighted imaging (DWI)
      and (18) F-FDG positron emission tomography (PET). MATERIALS AND METHODS: Forty
      one patients underwent simultaneous MR/PET after clinically indicated (18) F-FDG
      PET/CT. For all patients, histology of the primary tumor was obtained. MR
      protocol comprised anatomical imaging and axial DWI. Apparent diffusion
      coefficient (ADC) maps and FDG-PET were co-registered for evaluation of ADC and
      standard uptake value (SUV) of peritoneal lesions. Both lesion- and patient-based
      analysis was performed. Up to four peritoneal lesions were evaluated per patient.
      Mean and maximum standard uptake value (SUVmean , SUVmax ), mean and minimum ADC
      (ADCmean , ADCmin ) of each lesion were assessed. Spearman rank correlation (rs )
      of ADC and SUV were calculated. SUV and ADC of ovarian and colorectal cancer
      lesions were compared using Wilcoxon test. RESULTS: Measurable lesions (n = 52)
      were found in 20 of 41 PC patients. Moderate, but significant correlation existed
      between ADC and SUV in the lesion-based as well as the patient-based analysis
      (lesion-based: SUVmean versus ADCmean rs = -0.58; SUVmax versus ADCmin rs = 
      0.56, all P < 0.0001; patient-based: SUVmean versus ADCmean rs = -0.64, P =
      0.002; SUVmax versus ADCmin rs = -0.60, P = 0.005). ADC and SUV differed
      significantly between ovarian and colorectal cancer lesions (ADCmin : P < 0.0001;
      ADCmean : P < 0.0001; SUVmax : P = 0.002; SUVmean : P = 0.005). Overall, mucinous
      tumor entities showed a tendency to higher ADC and lower SUV. CONCLUSION: PC
      lesions showed significant differences in glucose uptake and diffusion
      characteristics depending on primary tumor histology. These differences should be
      considered when interpreting FDG-PET and DWI in PC patients.

PMID- 24923484
TI  - Glans-reconstruction with preputial flap is superior to primary closure for post
      surgical restoration of male sexual function in glans-preserving surgery.
AB  - We conducted this study to investigate whether glans-reconstruction with
      preputial flap would be more helpful for post-operative restoration of patients'
      sexual potency than primary closure. From 2007 to 2013 at four centres, 46 cases
      reconstructed with preputial flap and 59 with primary closure were selected for
      the investigation from 142 consecutive cases of superficial glans cancer, with
      the largest diameter of lesion <=2.5 cm, who undergoing glans-preserving surgery
      (GPS). Subjective evaluation for patients' sexual performance was investigated
      using the International Index of Erectile Function-15. Objective evaluation was
      carried out by the Audio Visual Sexual Stimulation test with RigiScan-Plus. The
      degree of satisfaction for penile appearance and patients' confidence and
      partners' acceptability for intercourse were evaluated by 5-point scales.
      Patients with preputial flap reconstruction showed significant better performance
      in three domains (orgasmic function, intercourse satisfaction and overall
      satisfaction, all p < 0.05) and significantly higher ratios of appearance
      satisfaction (78.3% vs. 57.6%, p = 0.026) and intercourse confidence (69.6% vs.
      49.2%, p = 0.035) compared with those undergoing primary closure at post
      operative month 6 ends. Their sexual partners in the preputial flap group also
      exhibited significantly higher ratios of appearance satisfaction than in the
      primary closure group (67.4% vs. 42.4%, p = 0.011). Reconstruction with preputial
      flap contributes to a more acceptable cosmetic appearance of the penis and
      minimizes post-operative negative psychological impediments. Patients can benefit
      more from reconstruction with preputial flap than primary closure. Glans
      reconstruction with preputial flap should be considered the primary
      reconstruction technique in GPS.

PMID- 24923485
TI  - Abstracts of the 10th International Podocyte Conference, June 4-6, 2014,
      Freiburg, Germany.

PMID- 24923486
TI  - STI-GMaS: an open-source environment for simulation of sexually-transmitted
      infections.
AB  - BACKGROUND: Sexually-transmitted pathogens often have severe reproductive health
      implications if treatment is delayed or absent, especially in females. The
      complex processes of disease progression, namely replication and ascension of the
      infection through the genital tract, span both extracellular and intracellular
      physiological scales, and in females can vary over the distinct phases of the
      menstrual cycle. The complexity of these processes, coupled with the common
      impossibility of obtaining comprehensive and sequential clinical data from
      individual human patients, makes mathematical and computational modelling
      valuable tools in developing our understanding of the infection, with a view to
      identifying new interventions. While many within-host models of sexually
      transmitted infections (STIs) are available in existing literature, these models
      are difficult to deploy in clinical/experimental settings since simulations often
      require complex computational approaches. RESULTS: We present STI-GMaS (Sexually
      Transmitted Infections - Graphical Modelling and Simulation), an environment for
      simulation of STI models, with a view to stimulating the uptake of these models
      within the laboratory or clinic. The software currently focuses upon the
      representative case-study of Chlamydia trachomatis, the most common sexually
      transmitted bacterial pathogen of humans. Here, we demonstrate the use of a
      hybrid PDE-cellular automata model for simulation of a hypothetical Chlamydia
      vaccination, demonstrating the effect of a vaccine-induced antibody in preventing
      the infection from ascending to above the cervix. This example illustrates the
      ease with which existing models can be adapted to describe new studies, and its
      careful parameterisation within STI-GMaS facilitates future tuning to
      experimental data as they arise. CONCLUSIONS: STI-GMaS represents the first
      software designed explicitly for in-silico simulation of STI models by non
      theoreticians, thus presenting a novel route to bridging the gap between
      computational and clinical/experimental disciplines. With the propensity for
      model reuse and extension, there is much scope within STI-GMaS to allow clinical
      and experimental studies to inform model inputs and drive future model
      development. Many of the modelling paradigms and software design principles
      deployed to date transfer readily to other STIs, both bacterial and viral;
      forthcoming releases of STI-GMaS will extend the software to incorporate a more
      diverse range of infections.

PMID- 24923487
TI  - A comprehensive hepatitis C virus risk factors meta-analysis (1989-2013): do they
      differ in Egypt?
AB  - BACKGROUND & AIMS: The prevention and control of HCV infection is complex and
      challenging in terms of describing risk factors and modes of transmission. This
      meta-analysis was conducted to summarize the best available data on HCV risk
      factors worldwide and in Egypt. METHODS: Through exhaustive literature searches
      (1989-2013) of HCV risk factors, 357 original eligible articles were included in
      this study. RESULTS: The highest detected risk was intravenous drug users (IDUs)
      (OR = 9.6) followed by HIV infection (OR = 4.9), having an IDU partner (OR =
      4.1), HBV infection (OR = 3.5), Caesarean section (CS) (OR = 3.35), blood
      transfusion (OR = 3.2) and having an HCV+ partner (OR = 3). Organ
      transplantation, hospital admission, haemodialysis and having a sexually
      transmitted infection carry 2.96, 2.4, 2.18 and 2 risks of having HCV
      respectively. Other significant risk factors included poor education, older age,
      sharing sharp or blunt objects, MSM, tattooing, hijama, body piercing, minor
      operations and medical procedures. Some risks showed a decrease over the previous
      decade, including blood transfusion, organ transplantation, IDUs, IDU partner and
      CS. Others showed rising risks, including having an HCV+ partner, MSM and
      suffering from STI. In Egypt, male gender, rural residence, acupuncture and
      receiving parenteral antischistosomal treatment were significant risks, while
      neither HIV nor HBV were found to carry a risk of HCV infection. CONCLUSION:
      Blood transfusion, organ transplantation, CS, IDUs, haemodialysis, minor
      operations and medical procedures are established risk factors. Attention and
      urgent intervention should be given to the sexual route of transmission, as well
      as that through minor operations and medical procedures.

PMID- 24923489
TI  - Determination of selenium via the fluorescence quenching effect of selenium on
      hemoglobin-catalyzed peroxidative reaction.
AB  - A new method for the determination of selenium based on its fluorescence
      quenching on the hemoglobin-catalyzed reaction of H2 O2 and l-tyrosine has been
      established. The effect of pH, foreign ions and the optimization of variables on
      the determination of selenium was examined. The calibration curve was found to be
      linear between the fluorescence quenching (F0 /F) and the concentration of
      selenium within the range of 0.16-4.00 ug/mL. The detection limit was 1.96 ng/mL
      and the relative standard deviation was 3.14%. This method can be used for the
      determination of selenium in Se-enriched garlic bulbs with satisfactory results.

PMID- 24923488
TI  - Discovery and validation of urinary metabotypes for the diagnosis of
      hepatocellular carcinoma in West Africans.
AB  - There is no clinically applicable biomarker for surveillance of hepatocellular
      carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too
      low for this purpose. Here, we determined the diagnostic performance of a panel
      of urinary metabolites of HCC patients from West Africa. Urine samples were
      collected from Nigerian and Gambian patients recruited on the case-control
      platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA)
      program. Urinary proton nuclear magnetic resonance ((1) H-NMR) spectroscopy was
      used to metabolically phenotype 290 subjects: 63 with HCC; 32 with cirrhosis
      (Cir); 107 with noncirrhotic liver disease (DC); and 88 normal control (NC)
      healthy volunteers. Urine samples from a further cohort of 463 subjects (141 HCC,
      56 Cir, 178 DC, and 88 NC) were analyzed, the results of which validated the
      initial cohort. The urinary metabotype of patients with HCC was distinct from
      those with Cir, DC, and NC with areas under the receiver operating characteristic
      (AUROC) curves of 0.86 (0.78-0.94), 0.93 (0.89-0.97), and 0.89 (0.80-0.98) in the
      training set and 0.81 (0.73-0.89), 0.96 (0.94-0.99), and 0.90 (0.85-0.96),
      respectively, in the validation cohort. A urinary metabolite panel, comprising
      inosine, indole-3-acetate, galactose, and an N-acetylated amino acid (NAA),
      showed a high sensitivity (86.9% [75.8-94.2]) and specificity (90.3% [74.2-98.0])
      in the discrimination of HCC from cirrhosis, a finding that was corroborated in a
      validation cohort (AUROC: urinary panel = 0.72; AFP =  0.58). Metabolites that
      were significantly increased in urine of HCC patients, and which correlated with
      clinical stage of HCC, were NAA, dimethylglycine, 1-methylnicotinamide,
      methionine, acetylcarnitine, 2-oxoglutarate, choline, and creatine. CONCLUSION:
      The urinary metabotyping of this West African cohort identified and validated a
      metabolite panel that diagnostically outperforms serum AFP.

PMID- 24923490
TI  - Ashkenazi Jewish population screening for Tay-Sachs disease: the international
      and Australian experience.
AB  - Internationally, Tay-Sachs disease (TSD) preconception screening of Ashkenazi
      Jewish (AJ) individuals and couples has led to effective primary prevention of
      TSD. In Australia, adolescent preconception genetic screening programs operate
      mainly in Jewish community high schools. These existing programs offer an
      effective means of primary prevention of TSD, are cost effective and safe.
      However, in the broader Australian community TSD screening is not systematically
      performed and cases still occur in unscreened AJ individuals. In order to improve
      the effectiveness of Australian screening, there is a need for definitive
      guidelines for healthcare professionals to facilitate extension of the proven
      benefits of preconception TSD screening to all AJ individuals at risk. We
      performed a systematic review of the relevant literature relating to AJ pre
      conception and antenatal screening for TSD. The evidence was assessed using an
      established National Health and Medical Research Council evidence grading system.
      Evaluations of efficacy of TSD screening programs design and execution, cost
      benefit and cost-utility health economic evaluation, and population outcomes were
      undertaken. The results have been used to propose a model for universal AJ TSD
      preconception and antenatal screening for the primary care setting. 

PMID- 24923491
TI  - Chest Radiological Findings of Patients With Severe H1N1 Pneumonia Requiring
      Intensive Care.
AB  - INTRODUCTION: A new strain of human influenza A (H1N1) virus originated from
      Mexico in 2009 and spread to more than 190 countries and territories. The World
      Health Organization (WHO) declared it a level 6 (highest level) pandemic. In
      August 2010, WHO announced that the H1N1 2009 influenza virus had moved into the
      postpandemic period. The WHO also declared that this flu strain is expected to
      continue to circulate as a seasonal virus "for some years to come." The objective
      of this study is to describe the chest radiographic and computed tomography (CT)
      findings of patients with severe H1N1 pneumonia admitted to the intensive care
      unit (ICU) during the 2009 pandemic. HYPOTHESIS: Patients with severe H1N1
      pneumonia requiring ICU admission have extensive radiographic and CT
      abnormalities. METHODS: Eighteen patients, aged 23 to 62 (mean 41), admitted to
      the ICU at UCLA-Olive View Medical Center with a primary diagnosis of pandemic
      H1N1 infection, confirmed either via rapid influenza detection test or by real
      time reverse transcriptase polymerase chain reaction assay, formed the study
      population. All patients had chest x-ray (CXR) within 24 hours of admission and 5
      patients had CT examinations. In this retrospective study, images were evaluated
      for the pattern (ground-glass opacities, consolidation, reticular opacities, and
      nodular opacities), distribution (unilateral/bilateral, upper/middle/lower lung
      zone, and central/peripheral/peribronchovascular), and extent
      (focal/multifocal/diffuse; number of lung zones) of abnormalities. RESULTS: All
      (100%) patients had abnormal CXR and CT studies. The predominant radiographic
      findings were ground-glass opacities (16 of 18; 89%), consolidation (16 of 18;
      89%), and reticular opacities (6 of 18, 33%). The radiographic abnormalities were
      bilateral in 17 (94%) patients; involved lower lung distribution in 18 (100%)
      patients, and mid and lower lung distribution in 16 (89%) patients. Radiographic
      abnormalities were peribronchovascular in 11 (61%) patients and multifocal in 10
      (56%). Sixteen (89%) patients had extensive abnormalities involving 3 or more
      lung zones. The patients requiring mechanical ventilation had a higher incidence
      of bilateral, diffuse consolidation in a peribronchovascular distribution on
      chest radiographs. The predominant CT abnormalities were consolidation (5 of 5;
      100%), ground-glass opacities (5 of 5; 100%), and nodular opacities (3 of 5,
      60%). The CT findings were peribronchovascular and multifocal in 4 (80%) patients
      and extensive and bilateral in all (100%) patients. CONCLUSIONS: Patients with
      H1N1 pneumonia admitted to the ICU had bilateral, extensive CXR, and CT
      abnormalities. Consolidations and ground-glass opacities were the most common
      imaging findings, predominantly affecting mid and lower lung zones. Imaging
      abnormalities were peribronchovascular and multifocal in a majority of patients.

PMID- 24923493
TI  - Cutaneous leishmaniasis mimicking a pyogenic granuloma.

PMID- 24923492
TI  - Cardiovascular Effects of Continuous Dexmedetomidine Infusion Without a Loading
      Dose in the Pediatric Intensive Care Unit.
AB  - BACKGROUND: Use of dexmedetomidine in pediatric critical care is common, despite
      lack of prospective studies on its hemodynamic effects. OBJECTIVE: To describe
      cardiovascular effects in critically ill children treated with a constant
      continuous infusion of dexmedetomidine without a loading dose at highest Food and
      Drug Administration-approved adult dose. METHODS: Prospective, pilot study of 17
      patients with dexmedetomidine infused at a rate of 0.7 MUg/kg/h for 6 to 24
      hours. Heart rate (HR) and blood pressure (BP) values over time were analyzed by
      a random effects mixed model. RESULTS: Patients with median age of 1.6 years (1
      month to 17 years) and median weight of 11.8 kg (2.8-84 kg) received an infusion
      for a mean of 16 +/- 7.2 hours. There were no cardiac conduction abnormalities.
      One patient required discontinuation of infusion for predetermined low HR
      termination criteria at hour 13 of infusion; there was no clinical compromise and
      it coincided with planned extubation. Decreased HR of 20% from baseline was found
      in 35% of patients. The mean HR reduction was largest at hour 13 of infusion with
      a decrease of 13 +/- 17 bpm from baseline, but HR changes over time were not
      statistically significant. Blood pressure effects included a decrease in 12% and
      an increase in 29%. There was a small but statistically significant increase in
      systolic BP of 0.4 mm Hg/h of infusion, P < .001. CONCLUSION: A continuous
      infusion of 0.7 MUg/kg/h of dexmedetomidine without a loading dose for up to 24
      hours in critically ill children had tolerable effects on HR and BP.

PMID- 24923494
TI  - Etude comparative de la densite de groupes de poissons cavernicoles et epiges
      (characidae, cyprinidae, clariidae).
AB  - The group density of four species of cave fishes (Caecobarbus geertsi, Barbopsis
      devecchii, Astyanax gen. and Uegitglanis zammaranoi) and of two taxonomically
      related epigean species (Barbus conchonius and Hyphessobricon scholzei) was
      measured tridimensionally in an experimental aquarium, using a video recorder and
      a mirror inclined at 45 degrees  placed on top of the aquarium. The experiments
      were conducted in dim red light. The illumination was continuous in the case of
      cave fishes. For the epigean forms a 12/12 LD cycle was superimposed using dim
      achromatic sources. The relative positions of individuals within their own
      specific group were registered hourly during a week (168 h). Results show that in
      cave forms, the mean density of groups falls within the theoretical limits of
      random distribution values in all cases, whereas epigean species display a non
      random aggregation tendency. 

PMID- 24923495
TI  - Question of "head preference" in response to worm-like dummies during prey
      capture of toads, Bufo bufo.
AB  - If a black worm-like dummy is moving against a white background, toads fixate and
      snap at the leading end of the stimulus. This "head preference" phenomenon is -
      within limits - independent of (i) background structure, and (ii) stripe length.
      "Head preference" can be disturbed by reducing the amount of the stimulus
      background contrast as well as by point structures incorporated in the worm-like
      shape of the stimulus. If the stimulus-background contrast of the worm dummy is
      reversed, toads exhibit a clear preference in fixating and snapping for the
      trailing end of the stimulus. This "tail preference" is independent of changes in
      (i) and (ii). The neural basis of "head preference" or "tail preference"
      respectively, is discussed. 

PMID- 24923496
TI  - Effects of nostril plugging and of habenulectomy on sexual behaviour in the male
      crested newt.
AB  - In an attempt to gain some insight into the possible involvement of the habenulae
      in the control of sexual behaviour in the male crested newt, a comparison was
      made between the effects of olfactory deprivation by bilateral nostril plugging
      and of habenulectomy on courtship performance and locomotor activity. Both
      treatments led to a decrease in spontaneous locomotion and to a drastic abolition
      of the complex courtship ritual characterized by the sequence of male postures
      displayed prior to spermatophore deposition. Following nostril plug removal, the
      animals resumed their normal activities. Unilateral plugging had no effect. These
      results seem to lend further support to the importance of specific olfactory
      stimuli in sexual behaviour. The main finding obtained here was the strict
      comparability between the behavioural changes resulting from habenulectomy and
      the olfactory-related changes following nostril plugging, linking from a
      functional point of view the habenulae with the olfactory system. According to
      recent reports available in the literature, the morphological organization of the
      habenular nuclei in urodeles still needs further clarification. On the basis of
      the present results, the possible importance of the habenulae in olfactory
      integration in the crested newt might be postulated. 

PMID- 24923497
TI  - Development of social behaviour in chickens: A factor analysis.
AB  - Factor analysis was used to describe the week by week changes in the frequency of
      a wide range of behaviours of chickens. Oblique rotation resulting in correlated
      factors was compared with the more conventional orthogonal rotation, and was
      found to provide a clearer interpretation of the factors. Mixed sex groups of
      chickens were observed from hatching until sexual maturity, and the changes in
      the occurrence of agonistic behaviours could be described in terms of three
      factors. Factor 1 involved early sparring and running, but there was some doubt
      as to whether this should be labelled aggressive. Factor 2 involved non
      reciprocated leaping, horizontal neck threats, and headpecks between males.
      Factor 3 involved threats and headpecks between males and females. Sexual
      development could be described by two factors; the first involving sexual
      development of the male, and the second the beginning of sexual interactions
      between males and females. Waltzes and rear approaches were associated with the
      sexual development of males, while chases were associated with sexual
      interactions. There was an increase in the frequency of prolonged male-male
      agonistic encounters when these sexual interactions began to occur. 

PMID- 24923498
TI  - Frequency and intensity of chick distress calls: Effects on maternal foodcalling
      in chickens.
AB  - The food call of broody domestic hens was used to measure maternal response to
      four frequency components found in chick distress calls (2,3,4 and 5 kHz) and to
      variations in distress call intensity (0-86 dB). Foodcalling increased
      significantly with frequency of the pure-tone test pulse; response to a taped
      distress call occurred between 40 dB and 86 dB intensity with a maximum at 60-65
      dB. The results suggest that the mother uses the higher frequency components in
      recognizing the distress call, but responds maximally within a specific intensity
      range. The selective advantage of such behaviour is discussed. 

PMID- 24923499
TI  - Effects of inter-trial interval length on food-hoarding partial reinforcement of
      running behaviour in the golden hamster.
AB  - Food-hoarding provides an adequate motivation in sated hamsters for the
      acquisition of a two-way running response. This learning was studied using a
      discrete-trial procedure, in continuous (CR) and partial reinforcement (PR)
      conditions, with two different inter-trial interval (ITI) lengths. The dependent
      variables were: the time spent by Ss in the goal section of the runway, and the
      number of their runs during extinction. The PR training had two effects on goal
      times: a slow decrease in acquisition on non-reinforced trials, and then a
      stabilization at this level during the extinction phase, as contrasted with the
      sudden increase found in CR-trained Ss when they were switched from acquisition
      to extinction conditions. However, the PR effects on number of runs depended upon
      ITI length: resistance to extinction of PR-trained Ss was superior to that of CR
      trained Ss with spaced, but not with massed, trials. In the latter case, CR
      trained Ss persisted as much as did PR-trained Ss. An hypothesis is offered,
      along the lines of the Frustration theory. 

PMID- 24923500
TI  - Spatial learning in golden hamsters: Relationship between food-searching
      strategies and difficulty of the task.
AB  - In an elevated maze consisting of three reconvergent radial arms, golden hamsters
      were tested with the same experimental rule: to choose each path without
      repeating any choice. However, variations of procedure concerning (a) the
      location of the reward in the maze, and (b) reinforcement contingencies, were
      introduced in order to define several problems involving variable levels of
      difficulty. The relationship between response strategies and difficulty of the
      task was then studied. The common learning criterion was the achievement of three
      consecutive correct daily sessions, each session corresponding to a particular
      sequence (pattern) of choices of paths. Response strategies were studied by
      analyzing the patterns obtained over the three final sessions in which an animal
      reached the learning criterion. Such a set of patterns (triplet) could be
      heterogeneous (patterns all different), mixed (two identical patterns, one
      different) or stereotyped (identical patterns). No relationship was found between
      the mean level of difficulty presented by each learning problem and the
      occurrence of a particular type of triplet. However, in each situation, mixed
      triplets were the most frequently recorded and corresponded to the medium
      individual speeds of learning whereas heterogeneous triplets corresponded to
      rapid successes and stereotyped triplets to delayed successes. These findings
      indicate that, whatever the problem designed to be tested in a three-arm maze,
      the various forms of solutions reflect different individual adaptative
      mechanisms. 

PMID- 24923501
TI  - Visual acuity and spatial contrast sensitivity in tree squirrels.
AB  - The visual sensitivity of tree squirrels from three different species (two
      western gray squirrels, Sciurus griseus; three fox squirrels, Sciurus niger; and
      an eastern gray squirrel, Sciurus carolinensis) was measured for spatial patterns
      defined by luminance differences. Spatial contrast sensitivity functions were
      determined in behavioral discrimination experiments in which the stimuli were
      sinusoidally-modulated gratings. At an average luminance level of 3.4 cd/m(2)
      these squirrels were maximally sensitive to spatial frequencies of about 0.5
      cycles/degree (c/d). These experiments, in conjunction with additional
      measurements involving discrimination of square-wave grating patterns, also
      indicate that the finest gratings these squirrels can discriminate average 2.2
      c/d (SD = 0.42 c/d). There are no obvious differences in resolution acuity among
      the three species. Grating acuity also was measured at a much higher luminance
      level (340 cd/m(2)). The results of this experiment indicate that the spatial
      acuity of the tree squirrel increases with luminance level, reaching a maximum of
      3.9 c/d at 340 cd/m(2). 

PMID- 24923502
TI  - Some aspects of individual behaviour during nest moving in the ant Tapinoma
      erraticum.
AB  - Tapinoma erraticum workers change their nest site if disturbed. Fewer than half
      of them displace the brood, with varying degrees of efficiency. In order to
      determine individual reactivity, the following measurements were carried out on
      each ant during a removal test: (1) seizures of larvae with the mandibles, (2)
      journeys between the two nests, (3) functional transports. A large number of
      seizures and a more rapid transport response are poorly correlated with high
      removal activity. In this situation, the journeys made between the two nests
      appear independent of transport activity. Each transporting worker was observed
      to show a characteristic transport rate which may vary during the test period.
      The extreme heterogeneity of all aspects of individual responses illustrates the
      probabilistic nature of the behaviour of social insects. 

PMID- 24923506
TI  - Handbook of sensory physiology Volume VII, 6A: Invertebrate photoreceptors
      (edited by H. Autrum); Volume VII, 6B: Invertebrate visual centers and behavior
      (I) (edited by H. Autrum); Volume VIII: Perception (edited by Richard Held, H.W.
      Leibowitz and H.L. Teuber). Springer Verlag, Berlin, Heidelberg, New York. 1979,
      729 pp., 344 figures; 1981, 629 pp., 319 figures; 1978, 993 pp., 254 figures and
      7 anaglyphs, respectively.

PMID- 24923508
TI  - L'animal et son univers: Etude dynamique du comportement Raymond Campan.
      Universite Paul Sabatier, Toulouse, France.

PMID- 24923509
TI  - Composite cryogels for lysozyme purification.
AB  - Beads-embedded novel composite cryogel was synthesized to purify lysozyme (Lyz)
      from chicken egg white. The poly(hydroxyethyl methacrylate-N-methacryloyl-L
      phenylalanine) (PHEMAPA) beads of smaller than 5 um size were synthesized by
      suspension polymerization and then embedded into a poly(hydroxyethyl
      methacrylate) (PHEMA)-based cryogel column. The PHEMAPA bead-embedded cryogel
      (BEC) column was characterized by swelling tests, scanning electron microscopy
      (SEM), surface area measurements by the Brunauer-Emmett-Teller (BET) method,
      elemental analysis, and flow dynamics. The specific surface area of the PHEMAPA
      BEC was found as 41.2 m(2) /g using BET measurements. Lyz-binding experiments
      were performed using aqueous solutions in different conditions such as initial
      Lyz concentration, pH, flow rate, temperature, and NaCl concentration of an
      aqueous medium. The PHEMAPA BEC column could be used after 10 adsorption
      desorption studies without any significant loss in adsorption capacity of Lyz.
      The PHEMAPA BEC column was used to purify Lyz from chicken egg white, and gel
      electrophoresis was used to estimate the purity of Lyz. The chromatographic
      application of the PHEMAPA BEC column was also performed using fast protein
      liquid chromatography.

PMID- 24923510
TI  - Photochemically-induced fluorescence properties of two benzoyl- and phenylurea
      pesticides and determination in natural waters.
AB  - A photo-induced fluorescence (PIF) method was developed for the determination of
      two benzoyl- and phenylurea pesticides, namely diflubenzuron (DFB) and fenuron
      (FEN). The photoconversion under UV irradiation of both pesticides into strongly
      fluorescent photoproducts was performed in several media (methanol, ethanol,
      acetonitrile, pH4 aqueous solution and pH4 water-methanol (30:70, v/v) mixture).
      PIF parameters were optimized. Analytical figures of merit for the PIF
      determination of DFB and FEN were satisfactory, with rather wide linear dynamic
      range (LDR) values of one to two orders of magnitude, relatively low limit of
      detection (LOD) values of, respectively, 9-24 ng/mL for DFB and 1-28 ng/mL for
      FEN, and limit of quantification (LOQ) values of, respectively, 30-80 ng/mL for
      DFB and 4-95 ng/mL for FEN, according to the medium. Relative standard deviation
      (RSD) values were in the range 1.7-5.6%. PIF was validated by comparing its
      analytical performances to those of a standard UV absorption spectrophotometric
      method. The optimized PIF method was applied to the quantitative analysis of both
      pesticides in various spiked natural water samples collected in a Senegal
      agricultural area by the standard addition procedure prior to extraction steps in
      dichloromethane, with satisfactory mean recovery percentage values (97.0-105.3
      for DFB and 98.3-102.8% for FEN). An interference study of foreign species,
      including pesticides and inorganic ions, likely to be present in natural waters,
      was also carried out.

PMID- 24923511
TI  - Detection of HSO4- ion based on the hydrolysis of diketopyrrolopyrrole-derived
      Schiff base with chromogenic and fluorogenic dual signals.
AB  - A new diketopyrrolopyrrole-based Schiff base L was synthesized and its anion
      sensing behavior was explored. L showed exclusive response toward HSO4(-) ion and
      also distinguished HSO4(-) from other anions by color changes (from dark red to
      orange) and 21 fold fluorescence enhancement at 370 nm in aqueous solution
      (THF/H2O = 8/1, v/v). The sensing mechanism was suggested to proceed via a
      hydrolysis process. The results provided colorimetric and fluorimetric assays to
      selectively detect the presence of a HSO4(-) over a wide range of other
      interfering anions. The results could potentially be used as a dual colorimetric
      fluorescent probe for monitoring HSO4(-) levels in physiological and
      environmental systems.

PMID- 24923512
TI  - To mate or fight? Male-male competition and alternative mating strategies in
      Argyrodes antipodiana (Theridiidae, Araneae).
AB  - Argyrodes antipodiana is a kleptoparasitic spider that builds its own web around
      the webs of other, larger host species. Males are more prone to have contests on
      webs of conspecific females than on webs of conspecific males. Males are also
      more likely to escalate interactions when on the females' webs than on males'
      webs, consistent with predictions from game theory models. Yet, in nearly half
      the tests, males on females' webs did not escalate. Instead of just being
      "sampling error", these failures to escalate may reflect the contest losers'
      abilities to gain copulations by "sneaking", an alternative mating tactic which
      enables males to obtain access to a female, not by fighting, but by exploiting
      the dominant male's dilemma of whether to mate or fight. 

PMID- 24923513
TI  - Self-directed behaviour and hippocampal electrical activity in rabbits living in
      a semi-natural environment.
AB  - Rabbits living in a semi-natural environment show a variety of behavioural
      elements related to voluntary or automatic movements. The aim of the present
      experiment was to study the hippocampal electrical correlates of self-directed
      activities occurring during spontaneous behaviour and emotional responses (the
      presence of a second rabbit of the same sex: intruder). Behaviour was divided
      into two broad categories. One included autocleaning elements such as scratching,
      shaking, washing and self-grooming. The other was characterized by consummatory
      activities: eating and drinking. Hippocampal activity was recorded by telemetry
      and the EEG periods related to specific behavioural elements were selected and
      analyzed. The electrical parameters were different for the various behavioural
      elements, for example rhythmic and irregular EEG patterns were recorded in
      different percentages during autocleaning and consummatory activities.
      Differences were also observed in the frequency peak distributions of power
      spectra. Confrontations influenced the occurrence of self directed behavioural
      elements and modified the pattern and frequency of hippocampal EEG during
      autocleaning activities. Results show that environmental variations can affect
      automatic behaviours and influence the mechanisms of hippocampal function. 

PMID- 24923514
TI  - Thresholds and escalation of antipredator responses in the Chinese salamander
      Cynops cyanurus: inter- and intra-individual variation.
AB  - Aspects of the control of antipredator behavior, including short- and long-term
      response modifications, were examined for the Chinese salamander Cynops cyanurus.
      Salamanders were tested for their antipredator behavior following repeated
      contact with the flicking tongue of a predatory snake. In a given trial, a
      salamander was contacted ten times by the snake and within-trial escalation or
      reduction in response was monitored. For each salamander, trials were repeated 6
      times at 21-day intervals to test for long-term changes in response threshold and
      extent of escalation, and to identify consistent differences in behavior among
      individuals. The salamanders were found to escalate their antipredator responses
      over the ten stimuli within trials. They were significantly more responsive to
      tongue contacts late in a given trial than to the initial stimuli. They also
      showed long-term, among-trial decreases in the threshold to initial response and
      increases in the mean responses to the first tongue contacts. However, there was
      no significant long-term change in maximum response threshold or in the mean
      responses to the final tongue contacts. Variation among individuals in thresholds
      and responses was considerable and was consistent over trials. 

PMID- 24923515
TI  - A hitherto unknown ethological factor in the ant Tetramorium impurum
      (Myrmicinae).
AB  - In Tetramorium impurum, an ethological factor can be found on workers' last
      visible abdominal sternite. For a short time, it attracts ants, increases their
      linear speed and enhances the efficiency of the trail pheromone. This factor is
      not colony-specific but may play a role in the foraging and recruiting systems of
      the species. 

PMID- 24923516
TI  - Results from a signal detection analysis approach to the study of lasting effects
      of early life undernutrition on the behaviour of rats.
AB  - Rats were undernourished from birth to 45 days of age, first by underfeeding
      their mothers (50% of ad libitum diet) and then, from weaning at 25 days, by
      feeding the pups a restricted diet. They were fed ad libitum from 45 days till
      the start of behavioural testing at 29 weeks. Eleven well-fed control (C) and 10
      previously undernourished (PU) male rats were trained to discriminate a brief
      decrement in light intensity. A response during this period was rewarded with
      food (a 'hit'); a response during an equivalent period in the absence of the
      signal (a 'false alarm') was penalised by delaying the onset of the next signal.
      Both groups of rats learned an easy discrimination equally well, but when the
      discrimination was made more difficult the PU rats required longer test sessions
      that C rats, made both more hits and more false alarms and had a higher
      responsivity index, indicating that the PU rats were more highly motivated than
      the C rats under this condition. Session duration increased on the more difficult
      discrimination; consequently time of day of testing changed somewhat and more for
      some rats than others. This may have been a confounding factor on the difficult
      discrimination and was specifically investigated in a follow-up experiment with
      the same rats. The results suggest that time may have been a conditioned stimulus
      and that the influence of this factor differed between C and PU rats. 

PMID- 24923517
TI  - Litter defence and parental investment allocation in house mice.
AB  - In house mice, post-partum maternal aggression against a potentially infanticidal
      male conspecific can be considered a parental investment act. As such, it
      constitutes a suitable experimental paradigm for testing parental investment
      allocation. In the present study, 60 nulliparous female albino mice were tested
      for maternal aggression on day 8 of the lactation period (single 5-min test
      exposure to a male intruder). Four experimental groups were created by
      manipulating the litter size. in two groups, litters were culled at birth to 4
      and 8 pups respectively, without any further pup removal. In the third group,
      litters were culled at birth to 8 pups, but 4 further pups were removed 3-4 hours
      before the test. In the fourth group, litters were manipulated as in the third
      group except that the 4 pups were returned to the litter after a 10-min removal.
      Dams with 8 pups at the time of testing showed significantly higher scores of
      aggressive behaviour than dams with 4 pups. The females of the two groups that
      had 4 pups at the time of testing did not differ in the intensity of maternal
      aggression. These results indicate that female house mice defend the investment
      made in their litters according to expected benefits (i.e., offspring number) and
      not to cumulative past investment. 

PMID- 24923518
TI  - Predatory versatility in the water bug Diplonychus indicus.
AB  - First instar Diplonychus indicus Venk. et Rao (Heteroptera:Belostomatidae) larvae
      possess a behavioural plasticity similar to that of adults. This highly versatile
      predator alternates frequently from foraging actively to ambushing and vice
      versa. No significant variations in the use of these two predatory modes during
      post-embryonic development could be evidenced. The present study stresses
      similarities between the use of different predatory modes by young and old larvae
      and by adults. Changes per unit time from one predatory mode to the other
      increased with age, as frequency of attempts increased with age. Adults changed
      predatory modes approximately seven times per hour. Most changes were made after
      one, two, or, more rarely, three predatory attempts of the same mode. The maximum
      number of consecutive attempts of one predatory mode increased with age. There
      was no evidence that any specialization occurred during development. No proximal
      causes for these changes of predatory mode were found. Changes were not
      correlated with the outcome of previous predatory attempts, nor did changing
      predatory mode increase the probability that the next attempt would be
      successful. 

PMID- 24923521
TI  - Synthesis, cytotoxic effects and tubulin polymerization inhibition of 1,4
      disubstituted 1,2,3-triazole analogs of 2-methoxyestradiol.
AB  - Thirteen 1,4-disubstituted 1,2,3-triazole analogs of 2-methoxyestradiol were
      prepared and tested for their cytotoxic and tubulin polymerization inhibition
      effects. Two compounds, 11j and 11k, exhibited anti-proliferative effects at low
      micromolar concentrations. The two analogs 11j and 11k also inhibited tubulin
      assembly with IC50 values of 8.1 and 5.9MUM, respectively. 

PMID- 24923522
TI  - Epigenetic modification of the leptin promoter in diet-induced obese mice and the
      effects of N-3 polyunsaturated fatty acids.
AB  - We report evidence of a detailed epigenetic modification of the leptin promoter
      and the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), which is closely
      associated with the leptin gene transcription in obesity. In the adipose tissue
      of diet induced obese (DIO) mice, methylation of the CpG island and the binding
      of methyl-CpG-binding domain protein 2 (MBD2) and DNA methyltransferases (DNMTs)
      at the leptin promoter are increased and RNA Pol II is decreased. Additionally,
      histones H3 and H4 are hypoacetylated, lysine 4 of histone H3 (H3K4) is
      hypomethylated and the binding of histone deacetylases (HDACs) 1, 2 and 6 is
      increased at the leptin promoter in the DIO mice. These modifications may serve a
      feedback role to maintain leptin concentrations within a normal range. The
      regulation of leptin transcriptional expression by n-3 PUFAs is mediated, at
      least in part, by epigenetic targets, such as MBD2 and histone modifications. 

PMID- 24923523
TI  - Cortical thickness correlates of psychotic experiences: examining the effect of
      season of birth using a genetically informative design.
AB  - Season of birth has been shown to influence risk for several neuropsychiatric
      diseases. Furthermore, it has been suggested that season of birth modifies a
      number of brain morphological traits. Since cortical thickness alterations have
      been reported across some levels of the psychosis-spectrum, this study was aimed
      at i) assessing the scarcely explored relationship between cortical thickness and
      severity of subclinical psychotic experiences (PEs) in healthy subjects, and ii)
      evaluating the potential impact of season of birth in the preceding thickness-PEs
      relationship. As both PEs and brain cortical features are heritable, the current
      work used monozygotic twins to separately evaluate familial and unique
      environmental factors. High-resolution structural MRI scans of 48 twins (24
      monozygotic pairs) were analyzed to estimate cortical thickness using FreeSurfer.
      They were then examined in relation to PEs, accounting for the effects of birth
      season; putative differential relationships between PEs and cortical thickness
      depending on season of birth were also tested. Current results support previous
      findings indicative of cortical thickening in healthy individuals with high
      psychometrically assessed psychosis scores, probably in line with theories of
      compensatory aspects of brain features in non-clinical populations. Additionally,
      they suggest distinct patterns of cortical thickness-PEs relationships depending
      on birth seasonality. Familial factors underlying the presence of PEs may drive
      these effects. 

PMID- 24923524
TI  - The use of real-time digital video in the assessment of post-operative outcomes
      of breast reconstruction.
AB  - INTRODUCTION: Outcome measures of breast reconstruction have used panel
      assessment of photographs. This provides limited information to the assessor as
      these images are static.. The aim of this study was to assess whether the use of
      digital video was a valid assessment tool and to compare its use against
      photography. METHODS: 35 patients post-reconstruction underwent photography,
      digital video capture and completed Breast Cancer Treatment Outcomes Scale
      (BCTOS) questionnaires. The photographs/video clips were randomised and shown to
      a 21 member panel. Opinions on aesthetic aspects of the reconstruction were
      assessed using the BCTOS and Harris scale. Panel inter-rater agreement and
      patient-panel correlation was assessed using Kendall's Coefficient of Concordance
      and Spearman's rank correlation tests respectively. RESULTS: There was a
      "moderate" degree of inter-rater agreement amongst panel members in all
      categories. Greater agreement occurred using video footage to assess overall
      cosmesis (0.548 vs 0.507) and shape (0.505 vs 0.486). Video showed a greater
      degree of correlation with patient self-assessment scores in comparison to
      photography (0.311 vs 0.281). CONCLUSION: Video footage coupled with panel
      assessment is a valid method of assessing post-operative outcomes of breast
      reconstruction and appears superior to still photographs in terms of inter-rater
      agreement and correlation with patient self-assessment.

PMID- 24923526
TI  - Preventing violence against women and girls in conflict.

PMID- 24923525
TI  - A retrospective study to classify surgical indications for infantile hemangiomas.
AB  - Infantile hemangiomas (IHs) spontaneously involute, but some leave contour
      deformities necessitating surgical correction. There is a paucity of data
      reviewing predictive risk factors associated with a need for surgery to guide
      clinicians when counseling parents. Patients undergoing IH resection by a single
      surgeon from August 2004 to August 2011 were reviewed to determine patient (age,
      gender, birth history) and IH characteristics (size, location) associated with
      surgical intervention. Data were compared to published data from the Hemangioma
      Investigator Group (HIG). Statistical analysis was performed using Student's t
      test, odds ratio, and logistic regression analysis. Out of 196 referred patients,
      112 underwent surgery. There was a female preponderance (3.5:1). Two-thirds of
      patients (64.9%) first presented to the surgeon at <=2 years of age, but most
      underwent surgery between 2 and 3 years (52.7%; average lag time, 11 months). 18
      patients underwent surgery at <=1 year of age. IH patients with preterm birth
      history had increased risk for needing surgical intervention (odds ratio 2.124,
      CI 1.31-3.44; p < 0.0012). A majority (84.7%) of resected IHs were located on the
      head or neck, significantly higher than the distribution from the HIG data
      (62.2%; p < 0.0001). Resected head and neck IHs were smaller than those below the
      neck (average, 8.85 cm(2) vs. 22.35 cm(2), p = 0.017). Preterm birth is
      associated with higher risk for requiring surgical intervention. IHs on the head
      and neck are more likely to be removed when compared to those below the neck, and
      at a smaller size threshold. 

PMID- 24923527
TI  - Responding to sexual violence in conflict.

PMID- 24923528
TI  - Muriel Volpellier: confronting sexual violence with evidence.

PMID- 24923529
TI  - Indicators linking health and sustainability in the post-2015 development agenda.
AB  - The UN-led discussion about the post-2015 sustainable development agenda provides
      an opportunity to develop indicators and targets that show the importance of
      health as a precondition for and an outcome of policies to promote sustainable
      development. Health as a precondition for development has received considerable
      attention in terms of achievement of health-related Millennium Development Goals
      (MDGs), addressing growing challenges of non-communicable diseases, and ensuring
      universal health coverage. Much less attention has been devoted to health as an
      outcome of sustainable development and to indicators that show both changes in
      exposure to health-related risks and progress towards environmental
      sustainability. We present a rationale and methods for the selection of health
      related indicators to measure progress of post-2015 development goals in non
      health sectors. The proposed indicators show the ancillary benefits to health and
      health equity (co-benefits) of sustainable development policies, particularly
      those to reduce greenhouse gas emissions and increase resilience to environmental
      change. We use illustrative examples from four thematic areas: cities, food and
      agriculture, energy, and water and sanitation. Embedding of a range of health
      related indicators in the post-2015 goals can help to raise awareness of the
      probable health gains from sustainable development policies, thus making them
      more attractive to decision makers and more likely to be implemented than before.

PMID- 24923530
TI  - Insight into the effects of adipose tissue inflammation factors on miR-378
      expression and the underlying mechanism.
AB  - BACKGROUND/AIMS: Obesity and the related metabolic syndrome have emerged as major
      public health issues in modern society. miRNAs have been shown to play key roles
      in regulating obesity-related metabolic syndrome, and some miRNAs regulated by
      adiponectin were identified as novel targets for controlling adipose tissue
      inflammation. miR-378 is a candidate target that was shown to be involved in
      adipose differentiation, mitochondrial metabolism and systemic energy
      homeostasis. However, little is known about the regulatory mechanisms of miR-378
      expression. To better understand the physiological role of miR-378 in obesity and
      metabolic syndrome, it is crucial that we understand the regulation of miR-378
      gene expression in human adipocytes. METHODS: In this study, we investigated the
      effects of adipokines and inflammatory cytokines on miR-378 expression using Real
      time PCR and the potential regulatory mechanisms using luciferase reporter assays
      and electrophoretic mobility shift assay (EMSA). Results : We found that
      adipokines and cytokines upregulated miR-378 expression primarily through SREBP
      and C/EBP binding sites in the miR-378 promoter region. CONCLUSION: Our findings
      showed that adipokines induced miR-378 expression and revealed the most likely
      mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs
      have been shown to function in regulating obesity-related metabolic syndrome, and
      miR-378 may be a novel target for controlling adipose tissue inflammation. This
      study offers a theoretical basis for understanding systemic adipose tissue
      inflammation and may provide new strategies for clinical treatment.

PMID- 24923531
TI  - Hematopoietic stem cells and liver regeneration: differentially acting
      hematopoietic stem cell mobilization agents reverse induced chronic liver injury.
AB  - Bone marrow (BM) could serve as a source of cells facilitating liver repopulation
      in case of hepatic damage. Currently available hematopoietic stem cell (HSC)
      mobilizing agents, were comparatively tested for healing potential in liver
      fibrosis. Carbon tetrachloride (CCl4)-injured mice previously reconstituted with
      Green Fluorescent Protein BM were mobilized with Granulocyte-Colony Stimulating
      Factor (G-CSF), Plerixafor or G-CSF+Plerixafor. Hepatic fibrosis, stellate cell
      activation and oval stem cell frequency were measured by Gomori and by
      immunohistochemistry for a-Smooth Muscle Actin and Cytokeratin-19, respectively.
      Angiogenesis was evaluated by ELISA and immunohistochemistry. Quantitative real
      time PCR was used to determine the mRNA levels of liver Peroxisome Proliferator
      Activated Receptor gamma (PPAR-gamma), Interleukin-6 (IL-6) and Tumor Necrosis
      alpha (TNFalpha). BM-derived cells were tracked by double immunofluorescence. The
      spontaneous migration of mobilized HSCs towards injured liver and its cytokine
      secretion profile was determined in transwell culture systems. Either single
      agent mobilization or the combination of agents significantly ameliorated hepatic
      damage by decreasing fibrosis and restoring the abnormal vascular network in the
      liver of mobilized mice compared to CCl4-only mice. The degree of fibrosis
      reduction was similar among all mobilized mice despite that G-CSF+Plerixafor
      yielded significantly higher numbers of circulating HSCs over other agents. The
      liver homing potential of variously mobilized HSCs differed among the agents. An
      extended G-CSF treatment provided the highest anti-fibrotic effect over all
      tested modalities, induced by the proliferation of hepatic stem cells and
      decreased hepatic inflammation. Plerixafor-mobilized HSCs, despite their reduced
      liver homing potential, reversed fibrosis mainly by increasing hepatic PPAR-gamma
      and VEGF expression. In all groups, BM-derived mature hepatocytes as well as
      liver-committed BM stem cells were detected only at low frequencies, further
      supporting the concept that alternative mechanisms rather than direct HSC effects
      regulate liver recovery. Overall, our data suggest that G-CSF, Plerixafor and G
      CSF+Plerixafor act differentially during the wound healing process, ultimately
      providing a potent anti-fibrotic effect. 

PMID- 24923532
TI  - Effects of two different blends of naturally mycotoxin-contaminated maize meal on
      growth and metabolic profile in replacement heifers.
AB  - The aim of this trial was to assess the effects of the administration of
      different combinations of mycotoxins in naturally contaminated maize grains on
      dairy heifer growth, blood measurements and puberty onset. A total of 35 Friesian
      female heifers were randomly allotted to three experimental groups from 18-21 to
      42-45 weeks of age. During the 24-week experimental period (EP), heifers were fed
      the same diet, but with maize meal derived from three differently contaminated
      lots: very low contamination, as control (C); medium-low aflatoxin-contaminated
      (A); and mixed aflatoxin-fumonisin contaminated (A-F). At the end of the EP, they
      returned to a common diet without contaminated maize, and they were monitored for
      an additional period of 12 weeks (post-experimental period, PEP). BW, wither
      height, hip height, body length and heart girth were measured every 4 weeks from
      the beginning of EP to the end of PEP. At the same time, body condition score was
      evaluated and blood samples were taken from the jugular vein to be analysed for
      haematological, serum protein and metabolic profiles. Age at puberty was assessed
      by measuring weekly plasma progesterone levels from 40 to 52 weeks of age. Body
      growth measurements were processed both by ANOVA of average daily gain of EP and
      PEP separately, and by the analysis of growth curve parameters. Haematological,
      serum protein and metabolic profile were evaluated using a mixed model, taking
      into account the repeated measurements in time on each animal. Heifers' growth
      was delayed both in A and A-F groups during EP, as evidenced by the different
      linear coefficients of the BW growth curve in the three groups. Differently
      contaminated diets did not affect the haematological profile, so that it can be
      concluded that these levels of mycotoxin contamination do not determine any
      specific effect on haematopoiesis and immunity in growing heifers. The main blood
      marker of mycotoxin chronic toxicity was the gamma-glutamyl transferase activity
      level in plasma, which appeared to be altered even after the removal of
      mycotoxins. During EP, plasma glucose was lower in the groups fed contaminated
      diet compared with C. The joint actions of an altered nutritional status and a
      long-lasting liver damage were probably the causes of the delay in puberty
      attainment in A and, particularly, in the A-F group. The results from this trial
      evidenced that a chronic aflatoxin-fumonisin contamination in diets of dairy
      heifers can determine an important delay in the reproductive career of these
      animals.

PMID- 24923533
TI  - Impact of comprehensive geriatric assessment on survival, function, and
      nutritional status in elderly patients with head and neck cancer: protocol for a
      multicentre randomised controlled trial (EGeSOR).
AB  - BACKGROUND: Survival is poorer in elderly patients with head and neck squamous
      cell carcinomas [HNSCCs] than in younger patients. Possible explanations include
      a contribution of co-morbidities to mortality, frequent refusal of standard
      therapy, and the use of suboptimal treatments due to concern about toxicities.
      The Comprehensive Geriatric Assessment [CGA] is a multidimensional assessment of
      general health that can help to customise treatment and follow-up plans. The CGA
      has been proven effective in several health settings but has not been evaluated
      in randomised studies of patients with cancer. Our aim here was to assess the
      impact of the CGA on overall survival, function, and nutritional status of
      elderly patients with HNSCC. METHODS/DESIGN: EGeSOR is an open-label,
      multicentre, randomised, controlled, parallel-group trial in patients aged 70
      years or older and receiving standard care for HNSCC. The intervention includes
      four components: the CGA conducted by a geriatrician before cancer treatment,
      participation of the same geriatrician in cancer treatment selection, a
      standardised geriatric therapeutic intervention designed by the same
      geriatrician; and geriatric follow-up for 24 months. The primary endpoint,
      assessed after 6 months, is a composite criterion including death, functional
      impairment [Activities of Daily Living score decrease >= 2], and weight loss >=
      10%. Secondary endpoints include progression-free survival, unscheduled
      admissions, quality of life, treatment toxicities, costs, and completion of the
      planned cancer treatment. A centralised online system is used to perform 1:1
      randomisation with a minimisation algorithm for centre, age, T and N stages, and
      tumour site [oral, oropharyngeal, hypopharyngeal, or laryngeal]. The estimated
      sample size is 704 patients, who are being recruited by 14 centres in 9 French
      cities. DISCUSSION: EGeSOR is the first randomised trial of the CGA in elderly
      cancer patients. We expect the CGA to have direct clinical benefits on the
      management of elderly patients with HNSCC. If this expectation is fulfilled, the
      trial may lead to modifications of the management model for elderly patients with
      cancer. TRIAL REGISTRATION: Trial registration: NCT02025062.

PMID- 24923534
TI  - Small kernel 1 encodes a pentatricopeptide repeat protein required for
      mitochondrial nad7 transcript editing and seed development in maize (Zea mays)
      and rice (Oryza sativa).
AB  - RNA editing modifies cytidines (C) to uridines (U) at specific sites in the
      transcripts of mitochondria and plastids, altering the amino acid specified by
      the DNA sequence. Here we report the identification of a critical editing factor
      of mitochondrial nad7 transcript via molecular characterization of a small kernel
      1 (smk1) mutant in Zea mays (maize). Mutations in Smk1 arrest both the embryo and
      endosperm development. Cloning of Smk1 indicates that it encodes an E-subclass
      pentatricopeptide repeat (PPR) protein that is targeted to mitochondria. Loss of
      SMK1 function abolishes the C -> U editing at the nad7-836 site, leading to the
      retention of a proline codon that is edited to encode leucine in the wild type.
      The smk1 mutant showed dramatically reduced complex-I assembly and NADH
      dehydrogenase activity, and abnormal biogenesis of the mitochondria. Analysis of
      the ortholog in Oryza sativa (rice) reveals that rice SMK1 has a conserved
      function in C -> U editing of the mitochondrial nad7-836 site. T-DNA knock-out
      mutants showed abnormal embryo and endosperm development, resulting in embryo or
      seedling lethality. The leucine at NAD7-279 is highly conserved from bacteria to
      flowering plants, and analysis of genome sequences from many plants revealed a
      molecular coevolution between the requirement for C -> U editing at this site and
      the existence of an SMK1 homolog. These results demonstrate that Smk1 encodes a
      PPR-E protein that is required for nad7-836 editing, and this editing is critical
      to NAD7 function in complex-I assembly in mitochondria, and hence to embryo and
      endosperm development in maize and rice. 

PMID- 24923535
TI  - The effect of inclined step stool on the quality of chest compression during in
      hospital cardiopulmonary resuscitation.
AB  - PURPOSE: A step stool is an ordinary device to improve the quality of chest
      compression (CC) during in-hospital cardiopulmonary resuscitation (CPR). We
      investigated the effect of an inclined step stool on the quality of CC during CPR
      on a hospital bed. METHODS: We conducted a randomized crossover study of
      simulation using a manikin. Two different methods of CC were performed and
      compared: CC using a flat stool and CC using an inclined (20 degrees ) stool.
      Each session of CC was performed for 2 minutes using a metronome at a rate of 110
      beats per minute. The primary outcome was the depth of CC. The adequate CC rate,
      duty cycle, rate of incomplete recoil, and the angle between the arm of the
      participants and the bed were also measured. RESULTS: The median value of the
      mean depth of CC was 50.5 mm (45.0-57.0 mm) in the flat stool group and 54.5 mm
      (47.0-58.3 mm) in the inclined stool group (P = .014). The adequate CC rate was
      significantly higher in the inclined stool group (84.2% [37.6%-99.1%] vs 57.0%
      [15.2%-95.0%]; P = .016). The duty cycle and the rate of incomplete recoil were
      comparable between the 2 groups. The angles between the arm of the participants
      and the bed were more vertical in the inclined stool group (84.0 degrees  +/- 5.2
      degrees  vs 81.0 degrees  +/- 4.8 degrees ; P = .014). CONCLUSION: Using an
      inclined stool resulted in an improvement in the depth of CC and the adequate CC
      rate without increasing the rate of incomplete chest recoil.

PMID- 24923536
TI  - Reduced-intensity conditioning hematopoietic cell transplantation is an effective
      treatment for patients with SLAM-associated protein deficiency/X-linked
      lymphoproliferative disease type 1.
AB  - X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency
      caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation
      (HCT) is often performed because of the morbidity and mortality associated with
      XLP1. There is limited experience using reduced-intensity conditioning (RIC)
      regimens for these patients. Here we report our 8-year single-center experience.
      Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between
      2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and
      melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH)
      after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage
      activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B
      cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was
      asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or
      related bone marrow grafts, whereas 2 patients received mismatched unrelated
      grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of
      methylprednisolone and cyclosporine in all but 1 patient, who additionally
      received methotrexate. All patients had hematopoietic recovery. There were no
      cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%)
      developed acute GVHD and later also developed chronic GVHD (6%). Five patients
      (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%)
      experienced a decline of donor chimerism to less than 50% but returned to full
      donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem
      cell boost. Infectious complications were frequent, particularly viral
      reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with
      long-term survival estimated at 71%. Survival was similar for patients with or
      without a history of HLH (86% versus 75%, respectively, P = .70). There were no
      occurrences of lymphoma or HLH after HCT. RIC HCT with alemtuzumab, fludarabine,
      and melphalan is an effective treatment for patients with XLP1, offering good
      survival rates regardless of prior disease manifestations, including HLH. 

PMID- 24923538
TI  - Everolimus in combination with mycophenolate mofetil as pre- and post
      transplantation immunosuppression after nonmyeloablative hematopoietic stem cell
      transplantation in canine littermates.
AB  - The mammalian target of rapamycin inhibitor everolimus (RAD001) is a successfully
      used immunosuppressant in solid-organ transplantation. Several studies have
      already used RAD001 in combination with calcineurin inhibitors after
      hematopoietic stem cell transplantation (HSCT). We investigated calcineurin
      inhibitor-free pre- and post-transplantation immunosuppression of RAD001 combined
      with mycophenolate mofetil (MMF) in a nonmyeloablative HSCT setting. After
      nonmyeloablative conditioning with 2 Gy total body irradiation, 8 dogs received
      HSCT from dog leukocyte antigen-identical siblings. Immunosuppressives were given
      at doses of 1.5 mg RAD001 twice daily from day -1 to +49, then tapered until day
      +56, and 20 mg/kg MMF from day 0 to +28, then tapered until day +42. An
      historical cyclosporin A (CsA)/MMF regimen was used in the control group. All
      dogs engrafted. Median platelet nadir amounted in all dogs to 0 * 10(9)/L
      (median, day +10; duration <50 * 10(9)/L, 22 days) and median leukocyte nadir was
      1.0 * 10(9)/L (range, .1 to 2.5 * 10(9)/L; median, day +13). Eventually, 5 of 8
      (63%) animals rejected their grafts. Two dogs died of infections on day +19 and
      +25. Pharmacokinetics of RAD001 and MMF showed median trough levels of 19.1
      (range, 10.5 to 43.2) MUg/L and .3 (.1 to 1.3) mg/L, respectively. The median
      area under the curve was 325 (range, 178 to 593) MUg/L * hour for RAD001 and 29.6
      (range, 7.9 to 40.5) ng/L * hour for MMF. All dogs developed clinically mucosal
      viral infections during the clinical course. Compared with the control group, the
      level of toxicities for RAD001/MMF increased in all qualities. Combined
      immunosuppression of RAD001 and MMF after nonmyeloablative HSCT is associated
      with significant toxicities, including a prolonged platelet recovery time as well
      as increased infections compared to the CsA/MMF regimen. 

PMID- 24923539
TI  - Restriction and dependence to autonomy and freedom: transformation in adolescent
      heart transplant recipients.
AB  - The process of heart transplantation poses numerous challenges and adaptive tasks
      for paediatric patients and their families. Few studies have examined how the
      experience of transplant interacts with developmental transitions such as
      adolescence, a period of significant change, and adjustment in itself. We
      explored adolescent heart transplant recipients' and their parents' experience of
      transplant from the point at which their heart condition was diagnosed to several
      months after transplantation. We adopted a developmental focus, to consider how
      participants negotiated the tasks of adolescence in the context of their
      transplant experiences. A qualitative approach was used to interview five
      adolescent-parent dyads, who reported few post-transplant complications, and the
      data were analysed according to the principles of IPA. Our findings revealed
      transplant to be a transformative experience, with two themes marking a contrast
      between pre- and post-transplant states: "Restriction and Dependence" and
      "Autonomy and Freedom." The themes are considered in relation to adolescent
      development. We propose that clinicians working with paediatric heart transplant
      recipients and their families need to consider the particular developmental
      challenges faced by adolescent patients and view the attainment of developmental
      milestones alongside physical and psychological markers of successful adjustment.

PMID- 24923537
TI  - Recipient pretransplant inosine monophosphate dehydrogenase activity in
      nonmyeloablative hematopoietic cell transplantation.
AB  - Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits
      inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting
      enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the
      oxidation of inosine 5'-monophosphate to xanthosine 5'-monophosphate (XMP). We
      developed a highly sensitive liquid chromatography-mass spectrometry method to
      quantitate XMP concentrations in peripheral blood mononuclear cells (PMNCs)
      isolated from the recipient pretransplant and used this method to determine IMPDH
      activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation
      (HCT) patients. The incubation procedure and analytical method yielded acceptable
      within-sample and within-individual variability. Considerable between-individual
      variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity
      was associated with increased day +28 donor T cell chimerism, more acute graft
      versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus
      reactivation but not with chronic GVHD, relapse, nonrelapse mortality, or overall
      mortality. We conclude that quantitation of the recipient's pretransplant IMPDH
      activity in PMNC lysate could provide a useful biomarker to evaluate a
      recipient's sensitivity to MMF. Further trials should be conducted to confirm our
      findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT
      recipients. 

PMID- 24923540
TI  - Behavioural processes.

PMID- 24923541
TI  - Influence of previous experience on the mate selection of two colour morphs of
      the convict cichlid, Cichlasoma nigrofasciatum (Pisces, Cichlidae).
AB  - In a pilot test, individuals of two colour morphs of Cichlasoma nigrofasciatum
      showed colour preferences in their schooling behaviour according to previous
      experience. Two further experiments were undertaken to investigate if such
      experientially induced preferences could reflect on the choice of mate. In one
      experiment white males who had been reared differently with regard to the colour
      morph of parents and siblings were given females of the different colour morphs
      (white and normal) to choose from, the females being successively removed after
      pairing to induce further choices. In this test, however, the males predominantly
      chose normal females, probably because of dominance relationships among the
      females, which masked a possible colour preference. Instead, a free choice test
      was devised, where 74 white and 74 normal fishes were allowed to pair off freely
      in a large tank. Here, a statistically significant sexual preference for the
      previously experienced colour morph was found. These results, as well as the
      possible evolutionary consequences, are discussed. 

PMID- 24923542
TI  - Motivation dependence of brain self-stimulation in the pigeon.
AB  - Several brain sites in the pigeon were identified as maintaining electrical brain
      self-stimulation. Depending on the site, stimulus currents yielding maximal
      responding varied from 20 to 160 MUA. A high proportion of the sites only yielded
      self-stimulation behaviour if the subjects were deprived of food; when the birds
      were at full weight there was only one site at which the stimulation continued to
      be rewarding. Some, but weak, evidence of stimulus satiation was found. Overt
      behaviour elicited by non-contingent stimulation did not correlate with the
      reinforcing or neutral nature of the sites tested. While some positive sites were
      associated with structures known to be involved in the control of feeding, others
      were not. The hypothesis that stimulation at the hunger-dependent sites might
      have elicited temporary satiation signals is considered. 

PMID- 24923543
TI  - Changes in emotionality following section of the tractus occipito-mesencephalicus
      in the barbary dove (Streptopelia risoria).
AB  - Section of the efferent pathways from the archistriatum in the Barbary Dove,
      leads to an immediate and persisting change in emotionality. The birds no longer
      react fearfully to the presence of a model predator, whereas control groups in
      which either the tractus occipito-mesencephalicus remains intact, or when the
      midline connections of the anterior commissure only are sectioned, continue to
      behave normally. This lack of responsiveness remains even under conditions of
      changing endogenous levels of hormone in the course of a normal breeding cycle. 

PMID- 24923544
TI  - Inhibition of adult social behaviour in ducks induced by juvenile administration
      of gonadal hormones.
AB  - This experiment was designed to study the long-term behavioural effects of
      gonadal hormone injections into domestic ducklings. Ten male and four female
      ducklings were injected daily from their 4th day onwards: the males with
      testosterone propionate and the females with oestradiol benzoate. Five males were
      injected for 40 days, the other ducklings (5? + 4?) for 80 days. Behavioural
      effects of these treatments were assessed when the birds were six months old.
      Social displays were strongly inhibited in the injected males as compared with
      control birds but no general significant effect was observed for the aggressive
      and sexual behaviour. The inhibition of social displays is consistent with the
      view that these behaviour patterns are regulated by the pituitary-gonadal axis
      and the different levels at which the functional inhibition could have occured
      are discussed. Far fewer social displays were performed by the males presented
      with injected females which, on the other hand, showed less sexual behaviour than
      the control females. This supports the idea that the female plays an important
      part in the social display of ducks. 

PMID- 24923545
TI  - Canid vocalizations.
AB  - The classification of acoustic signs is related to four aspects, the phonetic,
      the syntactic, the semantic, and the pragmatic. Canid vocalizations can be
      subdivided into 10 classes, which are described. The meaning and functions are
      considered in respect to releasing functions, control functions (in the
      cybernetic sense) and in relation to metabolism, reproduction and territory.
      Examples are given of age-specific sounds and of sound ontogeny. In addition, the
      metrics (entropies of information) are demonstrated in an example of sound
      sequence in the dog. 

PMID- 24923546
TI  - Vocalizations in wild canids and possible effects of domestication.
AB  - On the basis of spectrographic evidence it has been possible to identify twelve
      basic vocal sound types of canid species. Vocalizations may be mixed either by
      successive emission of two or more sound types, by superimposition of these
      sounds, or by a combination of these two forms. The same basic sound type may
      differ among canid species along the dimensions of sound duration, separation
      time between consecutive sounds, principle frequencies, cyclicity, and context.
      Developmental data indicate that domestic dogs first begin to mix sounds by
      successive sound emissions at about 10 days of age and later by superimposition
      between 2 and 3 weeks of age. The frequency of occurence of the basic sound types
      in different contexts varied between species but not within species. The possible
      effects of domestication on canid vocalizations are discussed. 

PMID- 24923547
TI  - The role of genetic factors in the determination of self-stimulation behaviour in
      the mouse: backcross analysis.
AB  - Intracranial self-stimulation behaviour in the lateral hypothalamus was studied
      in male mice obtained from a backcross between the F1 generation BALB/c J * DBA/2
      J and the strain BALB/c J, recessive for the majority of the self-stimulation
      parameters. The 48 animals of the backcross were divided into 3 groups at the 40
      MU A intensity. One group of 11 mice had mean performances similar to those of
      the recessive parental strain BALB/c. This result suggests that the genetic
      determination of the difference of self-stimulation performances observed between
      BALB/c and DBA/2 strains is not very complex. A negative correlation appeared
      between the thresholds and the performances of self-stimulation. Finally,
      stimulation intensities above 40 MU A triggered convulsion with similar
      frequencies in the three backcross groups. 

PMID- 24923548
TI  - Related factors and use of free preventive health services among adults with
      intellectual disabilities in Taiwan.
AB  - BACKGROUND: This study aimed to investigate the utilization of preventive health
      services in the adults with intellectual disabilities from the nationwide
      database. METHODS: The research method of this study is secondary data analysis.
      The data was obtained from three nationwide databases from 2006 to 2008. This
      study employed descriptive statistics to analyze the use and rate of preventive
      health services by intellectual disabled adults. Chi-square test was used to
      determine the relationship between the utilization of preventive health services
      and these variables. Multivariate logistic regression analysis was used to
      explore the factors that affect intellectual disabled adults' use of preventive
      health services. RESULTS: Our findings indicated 16.65% of people with
      intellectual disabilities aged over 40 years used the preventive health services.
      Females were more frequent users than males (18.27% vs. 15.21%, p <0.001). The
      utilization rate decreased with increasing severity of intellectual disabilities.
      The utilization was lowest (13.83%) for those with very severe disability,
      whereas that was the highest (19.38%) for those with mild severity. The factors
      significantly influencing utilization of the services included gender, age, and
      marital status, urbanization of resident areas, monthly payroll, low-income
      household status, catastrophic illnesses status and relevant chronic diseases and
      severity of disability. CONCLUSIONS: Although Taiwan's Health Promotion
      Administration (HPA) has provided free preventive health services for more than
      15 years, people with intellectual disabilities using preventive health care tend
      to be low. Demographics, economic conditions, health status, relevant chronic
      diseases, environmental factor, and severity of disability are the main factors
      influencing the use of preventive healthcare. According to the present findings,
      it is recommended that the government should increase the reimbursement of the
      medical staff performing health examinations for the persons with intellectual
      disabilities. It is also suggested to conduct media publicity and education to
      the public and the nursing facilities for the utilization of adult preventive
      health services.

PMID- 24923549
TI  - Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury
      in male F-344 rats following 12 weeks exposure.
AB  - Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has
      been shown to cause liver tumours in rodents and a small incidence of renal
      tubule tumours in male rats. The basis for the renal tubule injury is believed to
      be related to metabolism of TCE via glutathione conjugation to yield the cysteine
      conjugate that can be activated by the enzyme cysteine conjugate beta-lyase in
      the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH)
      have been shown to cause formic aciduria which can cause renal injury after
      chronic exposure in rats. In this study we have compared the renal toxicity of
      TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or
      formic aciduria can account for the toxicity. Male rats were given TCE
      (500mg/kg/day) or TCE-OH at (100mg/kg/day) for 12 weeks and the extent of renal
      injury measured at several time points using biomarkers of nephrotoxicity and
      prior to termination assessing renal tubule cell proliferation. The extent of
      formic aciduria was also determined at several time points, while renal pathology
      and plasma urea and creatinine were determined at the end of the study. TCE
      produced a very mild increase in biomarkers of renal injury, total protein, and
      glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine
      after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase
      in these biomarkers in urine. However, both chemicals produced a marked and
      sustained increase in the excretion of formic acid in urine to a very similar
      extent. The activity of methionine synthase in the liver of TCE and TCE-OH
      treated rats was inhibited by about 50% indicative of a block in folate
      synthesis. Both renal pathology and renal tubule cell proliferation were reduced
      after TCE and TCE-OH treatment compared to controls. Our findings do not clearly
      identify the pathway which is responsible for the renal toxicity of TCE but do
      provide some support for metabolism via glutathione conjugation. 

PMID- 24923550
TI  - Quantitative phosphoproteomic profiling of fiber differentiation and initiation
      in a fiberless mutant of cotton.
AB  - BACKGROUND: The cotton (Gossypium spp.) fiber cell is an important unicellular
      model for studying cell differentiation. There is evidence suggesting that
      phosphorylation is a critical post-translational modification involved in
      regulation of a wide range of cell activities. Nevertheless, the sites of
      phosphorylation in G. hirsutum and their regulatory roles in fiber cell
      initiation are largely unknown. In this study, we employed a mass spectrometry
      based phosphoproteomics to conduct a global and site-specific phosphoproteome
      profiling between ovules of a fuzzless-lintless (fl) Upland cotton (G. hirsutum)
      mutant and its isogenic parental wild type (WT) at -3 and 0 days post-anthesis
      (DPA). RESULTS: A total of 830 phosphopeptides and 1,592 phosphorylation sites
      from 619 phosphoproteins were identified by iTRAQ (isobaric tags for relative and
      absolute quantitation). Of these, 76 phosphoproteins and 1,100 phosphorylation
      sites were identified for the first time after searching the P3DB public database
      using the BLAST program. Among the detected phosphopeptides, 69 were
      differentially expressed between the fl mutant and its WT in ovules at -3 and 0
      DPA. An analysis using the Motif-X program uncovered 19 phosphorylation motifs, 8
      of which were unique to cotton. A further metabolic pathway analysis revealed
      that the differentially phosphorylated proteins were involved in signal
      transduction, protein modification, carbohydrate metabolic processes, and cell
      cycle and cell proliferation. CONCLUSIONS: Our phosphoproteomics-based research
      provides the first global overview of phosphorylation during cotton fiber
      initiation, and also offers a helpful dataset for elucidation of signaling
      networks in fiber development of G. hirsutum.

PMID- 24923551
TI  - Pharmacologically distinct phenotypes of alpha1B -adrenoceptors: variation in
      binding and functional affinities for antagonists.
AB  - BACKGROUND AND PURPOSE: The pharmacological properties of particular receptors
      have recently been suggested to vary under different conditions. We compared the
      pharmacological properties of the alpha1B -adrenoceptor subtype in various tissue
      preparations and under various conditions. EXPERIMENTAL APPROACH: [(3) H]
      prazosin binding to alpha1B -adrenoceptors in rat liver (segments, dispersed
      hepatocytes and homogenates) was assessed and the pharmacological profiles were
      compared with the functional and binding profiles in rat carotid artery and
      recombinant alpha1B -adrenoceptors. KEY RESULTS: In association and saturation
      binding experiments with rat liver, binding affinity for [(3) H]-prazosin varied
      significantly between preparations (KD value approximately ten times higher in
      segments than in homogenates). The binding profile for various drugs in liver
      segments also deviated from the representative alpha1B -adrenoceptor profile
      observed in liver homogenates and recombinant receptors. L-765,314 and ALS-77,
      selective antagonists of alpha1B -adrenoceptors, showed high binding and
      antagonist affinities in liver homogenates and recombinant alpha1B 
      adrenoceptors. However, binding affinities for both ligands in the segments of
      rat liver and carotid artery were 10 times lower, and the antagonist potencies in
      alpha1B -adrenoceptor-mediated contractions of carotid artery were more than 100
      times lower than the representative alpha1B -adrenoceptor profile. CONCLUSIONS
      AND IMPLICATIONS: In contrast to the consistent profile of recombinant alpha1B 
      adrenoceptors, the pharmacological profile of native alpha1B -adrenoceptors of
      rat liver and carotid artery varied markedly under various receptor environments,
      showing significantly different binding properties between intact tissues and
      homogenates, and dissociation between functional and binding affinities. In
      addition to conventional 'subtype' characterization, 'phenotype' pharmacology
      must be considered in native receptor evaluations in vivo and in future
      pharmacotherapy.

PMID- 24923552
TI  - Evidence of cryptic speciation in mesostigmatid mites from South Africa.
AB  - Laelaps giganteus and Laelaps muricola (Mesostigmata; Laelapidae) are widespread
      and locally abundant host generalists on small mammals in southern Africa. The
      large host range and complex life history of these ectoparasites may allude to
      possible intraspecific cryptic diversity in these taxa. To assess genetic and
      morphological diversity in L. giganteus and L. muricola, we sampled 228 rodents
      at eight localities in South Africa. This sample included nine previously
      recorded host species and on these, L. muricola was only recorded from Mastomys
      natalensis and Micaelamys namaquensis while L. giganteus was found on Rhabdomys
      dilectus and Lemniscomys rosalia. Phylogenetic analyses of partial mtDNA
      cytochrome oxidase subunit I (COI) and nuclear ITS1 data strongly supported the
      recognition of L. giganteus and L. muricola, a scenario partly supported by the
      Tropomyosin intron. Strong support for evolutionary distinct lineages within L.
      giganteus is found: L. giganteus lineage 1 is confined to R. dilectus and L.
      giganteus lineage 2 is confined to L. rosalia. These host specific monophyletic
      lineages were also separated by 9.84% mtDNA sequence divergence and 3.44% nuclear
      DNA sequence divergence. Since quantitative morphometric analyses were not
      congruent with these findings, these two lineages more than likely represent
      cryptic species.

PMID- 24923553
TI  - Enhanced oxidative stress and platelet activation in patients with Cushing's
      syndrome.
AB  - OBJECTIVE: Cushing Syndrome (CS) is implicated by increased cardiovascular risk
      (CVR) leading to increased morbidity and mortality. Oxidative stress (OS) and
      platelet activation (PA) are associated with increased CVR. However, scarce data
      of OS in CS exist. Our objective was to determine the oxidant-antioxidant balance
      in CS. DESIGN: Fourteen patients with CS at diagnosis and fourteen healthy
      subjects (NS) were evaluated OS by measuring plasma 15-F2t -Isoprostane (15-F2t 
      IsoP), PA by thromboxaneB2 levels (TXB2 ), and antioxidant reserve measuring
      total antioxidant capacity (TAC) and serum vitamin E. RESULTS: 15-F2t -IsoP and
      TXB2 levels were significantly higher (P < 0.01) in CS, while vitamin E levels
      were higher in NS (P < 0.03). 15-F2t -IsoP levels were significantly higher (P <
      0.01) in complicated vs not-complicated CS and NS and significantly higher (P <
      0.03) in CS not-complicated vs NS. TXB2 levels were significantly reduced (P <
      0.03) in NS vs complicated and not-complicated CS. A negative correlation between
      Vitamin E and UFC was observed in CS (P < 0.05 r = -0.497). TXB2 correlated with
      glucose, HbA1c and T-score (P < 0.05 r = 0.512, P < 0.03 r = 0.527 and P < 0.01 r
      = 0.783, respectively) and HDL (P < 0.01 r = -0.651). 15-F2t -IsoP correlated
      with triglicerides, HbA1c and diastolic pressure (P < 0.01 r = 0.650, P < 0.03 r
      = 0.571 and P < 0.05 r = 0.498, respectively) and HDL (P < 0.03 r = -0.594).
      CONCLUSIONS: This study emphasizes the major role of OS in CS. As our findings
      demonstrated that enhanced OS and PA take place in this rare metabolic disorder
      which is associated with increased CVR, it could be suggested that these
      biochemical alterations can further contribute in the pathogenesis of
      atherosclerosis, increased CVR and mortality in CS.

PMID- 24923554
TI  - SOS, the formidable strategy of bacteria against aggressions.
AB  - The presence of an abnormal amount of single-stranded DNA in the bacterial cell
      constitutes a genotoxic alarm signal that induces the SOS response, a broad
      regulatory network found in most bacterial species to address DNA damage. The aim
      of this review was to point out that beyond being a repair process, SOS induction
      leads to a very strong but transient response to genotoxic stress, during which
      bacteria can rearrange and mutate their genome, induce several phenotypic changes
      through differential regulation of genes, and sometimes acquire characteristics
      that potentiate bacterial survival and adaptation to changing environments. We
      review here the causes and consequences of SOS induction, but also how this
      response can be modulated under various circumstances and how it is connected to
      the network of other important stress responses. In the first section, we review
      articles describing the induction of the SOS response at the molecular level. The
      second section discusses consequences of this induction in terms of DNA repair,
      changes in the genome and gene expression, and sharing of genomic information,
      with their effects on the bacteria's life and evolution. The third section is
      about the fine tuning of this response to fit with the bacteria's 'needs'.
      Finally, we discuss recent findings linking the SOS response to other stress
      responses. Under these perspectives, SOS can be perceived as a powerful bacterial
      strategy against aggressions. 

PMID- 24923556
TI  - Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary
      resuscitation is robust to GPR30 gene deletion.
AB  - INTRODUCTION: Acute kidney injury is a serious,sexually dimorphic perioperative
      complication, primarily attributed to hypoperfusion. We previously found that
      estradiol is renoprotective after cardiac arrest and cardiopulmonary
      resuscitation in ovariectomized female mice. Additionally, we found that neither
      estrogen receptor alpha nor beta mediated this effect. We hypothesized that the G
      protein estrogen receptor (GPR30) mediates the renoprotective effect of estrogen.
      METHODS: Ovariectomized female and gonadally intact male wild-type and GPR30 gene
      deleted mice were treated with either vehicle or 17beta-estradiol for 7 days,
      then subjected to cardiac arrest and cardiopulmonary resuscitation. Twenty four
      hours later, serum creatinine and urea nitrogen were measured, and histologic
      renal injury was evaluated by unbiased stereology. RESULTS: In both males and
      females, GPR30 gene deletion was associated with reduced serum creatinine
      regardless of treatment. Estrogen treatment of GPR30 gene-deleted males and
      females was associated with increased preprocedural weight. In ovariectomized
      female mice, estrogen treatment did not alter resuscitation, but was
      renoprotective regardless of GPR30 gene deletion. In males, estrogen reduced the
      time-to-resuscitate and epinephrine required. In wild-type male mice, serum
      creatinine was reduced, but neither serum urea nitrogen nor histologic outcomes
      were affected by estrogen treatment. In GPR30 gene-deleted males, estrogen did
      not alter renal outcomes. Similarly, renal injury was not affected by G1 therapy
      of ovariectomized female wild-type mice. CONCLUSION: Treatment with 17beta
      estradiol is renoprotective after whole-body ischemia-reperfusion in
      ovariectomized female mice irrespective of GPR30 gene deletion. Treatment with
      the GPR30 agonist G1 did not alter renal outcome in females. We conclude GPR30
      does not mediate the renoprotective effect of estrogen in ovariectomized female
      mice. In males, estrogen therapy was not renoprotective. Estrogen treatment of
      GPR30 gene-deleted mice was associated with increased preprocedural weight in
      both sexes. Of significance to further investigation, GPR30 gene deletion was
      associated with reduced serum creatinine, regardless of treatment.

PMID- 24923558
TI  - The re-emerging role of microbial natural products in antibiotic discovery.
AB  - New classes of antibacterial compounds are urgently needed to respond to the high
      frequency of occurrence of resistances to all major classes of known antibiotics.
      Microbial natural products have been for decades one of the most successful
      sources of drugs to treat infectious diseases but today, the emerging unmet
      clinical need poses completely new challenges to the discovery of novel
      candidates with the desired properties to be developed as antibiotics. While
      natural products discovery programs have been gradually abandoned by the big
      pharma, smaller biotechnology companies and research organizations are taking
      over the lead in the discovery of novel antibacterials. Recent years have seen
      new approaches and technologies being developed and integrated in a
      multidisciplinary effort to further exploit microbial resources and their
      biosynthetic potential as an untapped source of novel molecules. New strategies
      to isolate novel species thought to be uncultivable, and synthetic biology
      approaches ranging from genome mining of microbial strains for cryptic
      biosynthetic pathways to their heterologous expression have been emerging in
      combination with high throughput sequencing platforms, integrated bioinformatic
      analysis, and on-site analytical detection and dereplication tools for novel
      compounds. These different innovative approaches are defining a completely new
      framework that is setting the bases for the future discovery of novel chemical
      scaffolds that should foster a renewed interest in the identification of novel
      classes of natural product antibiotics from the microbial world. 

PMID- 24923557
TI  - Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.
AB  - Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion
      cells (RGCs) accounts for visual impairment of glaucoma. Here, we report
      rapamycin protects RGCs from death in experimental glaucoma model and the
      underlying mechanisms. Our results showed that treatment with rapamycin
      dramatically promote RGCs survival in a rat chronic ocular hypertension model.
      This protective action appears to be attributable to inhibition of neurotoxic
      mediators release and/or direct suppression of RGC apoptosis. In support of this
      mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF
      alpha in BV2 microglials by modulating NF-kappaB signaling. In experimental
      animals, treatment with rapamycin also dramatically inhibited the activation of
      microglials. In primary RGCs, rapamycin was capable of direct suppression the
      apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin
      mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a
      site critical for maintenance of its survival-promoting activity in cell and
      animal model. These results demonstrate that rapamycin is neuroprotective in
      experimental glaucoma, possibly via decreasing neurotoxic releasing and
      suppressing directly apoptosis of RGCs. 

PMID- 24923559
TI  - Fumarate metabolism and ATP production in Pseudomonas fluorescens exposed to
      nitrosative stress.
AB  - Although nitrosative stress is known to severely impede the ability of living
      systems to generate adenosine triphosphate (ATP) via oxidative phosphorylation,
      there is limited information on how microorganisms fulfill their energy needs in
      order to survive reactive nitrogen species (RNS). In this study we demonstrate an
      elaborate strategy involving substrate-level phosphorylation that enables the
      soil microbe Pseudomonas fluorescens to synthesize ATP in a defined medium with
      fumarate as the sole carbon source. The enhanced activities of such enzymes as
      phosphoenolpyruvate carboxylase and pyruvate phosphate dikinase coupled with the
      increased activities of phospho-transfer enzymes like adenylate kinase and
      nucleoside diphophate kinase provide an effective strategy to produce high energy
      nucleosides in an O2-independent manner. The alternate ATP producing machinery is
      fuelled by the precursors derived from fumarate with the aid of fumarase C and
      fumarate reductase. This metabolic reconfiguration is key to the survival of P.
      fluorescens and reveals potential targets against RNS-resistant organisms. 

PMID- 24923560
TI  - A novel functional role for MMSET in RNA processing based on the link between the
      REIIBP isoform and its interaction with the SMN complex.
AB  - The chromosomal translocation t(4;14) deregulates MMSET (WHSC1/NSD2) expression
      and is a poor prognostic factor in multiple myeloma (MM). MMSET encodes two major
      protein isoforms. We have characterized the role of the shorter isoform (REIIBP)
      in myeloma cells and identified a clear and novel interaction of REIIBP with
      members of the SMN (survival of motor neuron) complex that directly affects the
      assembly of the spliceosomal ribonucleic particles. Using RNA-seq we show that
      REIIBP influences the RNA splicing pattern of the cell. This new discovery
      provides novel insights into the understanding of MM pathology, and potential new
      leads for therapeutic targeting. 

PMID- 24923561
TI  - A source of the single-stranded DNA substrate for activation-induced deaminase
      during somatic hypermutation.
AB  - During somatic hypermutation (SHM), activation-induced deaminase (AID) mutates
      deoxycytidine on single-stranded DNA (ssDNA) generated by the transcription
      machinery, but the detailed mechanism remains unclear. Here we report a higher
      abundance of RNA polymerase II (Pol II) at the immunoglobulin heavy-chain
      variable (Igh-V) region compared with the constant region and partially
      transcribed Igh RNAs, suggesting a slower Pol II progression at Igh-V that could
      result in some early/premature transcription termination after prolonged
      pausing/stalling of Pol II. Knocking down RNA-exosome complexes, which could
      decrease premature transcription termination, leads to decreased SHM. Knocking
      down Spt5, which can augment premature transcription termination, leads to
      increase in both, SHM and the abundance of ssDNA substrates. Collectively, our
      data support the model that, following the reduction of Pol II progression
      (pausing or stalling) at the Igh-V, additional steps such as premature
      transcription termination are involved in providing ssDNA substrates for AID
      during SHM. 

PMID- 24923562
TI  - Circulating biomarkers in hepatocellular carcinoma.
AB  - PURPOSE: Our aims are to determine levels of circulating cellular and protein
      biomarkers in hepatocellular carcinoma (HCC) patients and to analyse any
      relationships with clinical parameters. METHODS: Fifty-four consenting patients
      were recruited. Circulating tumour cells (CTCs) were enumerated (by CellSearch)
      and characterised via filtration [by isolation by size of epithelial tumour cells
      (ISET)] with downstream immunohistochemistry (IHC). Glypican-3 (GPC3) expression
      in tumour biopsies and CTCs (by IHC) was compared, and levels of circulating
      caspase-cleaved and full-length cytokeratin 18 (CK18, measured using M30 and M65
      ELISAs) were examined as a putative prognostic factor and marker of tumour
      burden. RESULTS: CTCs were identified in 14 out of 50 (28%) patients by
      CellSearch and in 19 out of 19 (100%) patients by ISET. The presence of GPC3
      positive CTCs by ISET was 100% concordant with the presence of GPC3-positive
      cells in the original tumour (n = 5). No statistically significant correlations
      were observed between CTC number and clinical characteristics, although trends
      were noted between CTC subtypes, Child-Pugh score and tumour node metastasis
      stage. Serum M30 and M65 levels (as continuous variables) significantly
      correlated with overall survival (OS) in a univariate analysis (p = 0.003 and p <
      0.001, respectively); M65 levels remained statistically significant in a
      multivariate analysis (p = 0.029). CONCLUSIONS: This is the first study to detect
      GPC3-positive CTCs in HCC, important for drug development with this target. The
      significant association of circulating CK18 with OS in HCC further exemplifies
      the utility of circulating biomarkers in cancer.

PMID- 24923563
TI  - The role of wearable sensors and wireless technologies for the assessment of
      heart rate variability in anorexia nervosa.
AB  - PURPOSE: Bradycardia and abnormal cardiac autonomic function are related to
      increased mortality in anorexia nervosa (AN). The aim of this study was to assess
      heart rate (HR) and HR variability of young adolescents with AN as compared to
      controls by means of wearable sensors and wireless technologies. METHOD: The ECG
      signal was recorded in 27 AN girls and 15 healthy girls at rest using a wearable
      chest strap. The tachogram, the mean intervals between R peaks (meanRR), the root
      mean square of successive differences (RMSSD), the power of low-frequency (LF)
      and high-frequency (HF) bands and the LF/HF ratio were assessed. RESULTS: All AN
      girls showed a reduced HR and an increased meanRR and RMSSD. An HF increase, a LF
      decrease, and a LF/HF reduction indicated a prevalence of the parasympathetic on
      sympathetic activity. CONCLUSIONS: The instruments used in this pilot study were
      feasible, unobtrusive and extremely suitable in AN subjects who are burdened by
      high incidence of cardiovascular mortality; their application could open to new
      approaches of vital signs monitoring in hospitals as well as in home settings.

PMID- 24923565
TI  - Oxidative stress in biology and medicine.

PMID- 24923566
TI  - Cell culture, oxidative stress, and antioxidants: avoiding pitfalls.
AB  - Cell culture is widely used by biochemists and cell/molecular biologists, but the
      fluctuating (and often elevated) levels of O 2 to which cells in culture are
      exposed can affect many of their properties. So can the low level of antioxidants
      found in some cell culture media. Reagents, especially "antioxidants," added to
      cell culture media can react with the constituents of the media to produce H 2 O
      2 and degradation products that can influence cell behavior. Several published
      papers describing the cellular effects of ascorbate, polyphenols, and carotenoids
      have, in fact, reported artifacts due to the actions of the degradation products
      of these "antioxidants." A greater awareness of the potential artifacts in cell
      culture studies is needed among the free radical/antioxidant community.

PMID- 24923567
TI  - Antioxidants: basic principles, emerging concepts, and problems.
AB  - The radical scavenging antioxidants play an essential role in the maintenance of
      health and prevention of diseases, and a thorough understanding of the action and
      capacity of antioxidants is critically important. Despite the assumption that
      antioxidants must exert beneficial effects against oxidative stress, many large
      scale randomized controlled trials gave inconsistent and disappointing results on
      the prevention of chronic diseases. It is now generally accepted that there is no
      evidence to support the use of non-discriminative antioxidant supplements for
      prevention of diseases. On the other hand, recent data show that antioxidants may
      be effective in the prevention and/or treatment of diseases when the right
      antioxidant is given to the right subject at the right time for the right
      duration. Now it is accepted that reactive oxygen species (ROS) act as
      physiologically important signaling messengers as well as deleterious agents. The
      signaling ROS are produced in a subtly regulated manner, while many deleterious
      ROS are produced and react randomly. Free radical-mediated lipid peroxidation
      products which, in contrast to enzymatic oxidation products, are produced by non
      specific mechanisms cause oxidative damage, but may also induce adaptive response
      to enhance the expression of antioxidant enzymes and compounds. This has raised a
      question if removal of too many ROS by supplementation of antioxidants may upset
      the cell signaling pathways and actually increase the risk of chronic diseases.
      However, it is unlikely that antioxidants impair physiologically essential
      signaling pathways.

PMID- 24923569
TI  - Pros and cons of current approaches for detecting peroxynitrite and their
      applications.
AB  - Peroxynitrite, a representative of reactive nitrogen species, plays important
      roles in the physiological and pathological processes of many oxidative stress
      related diseases. It is generated from the reaction of nitric oxide (NO) and
      superoxide (O2.-) and is far more active than its precursors. Peroxynitrite can
      be further decomposed into other cytotoxic reactive species. Peroxynitrite and
      its derivatives can interact with various biomolecules such as DNA and proteins.
      Due to its high reactivity and short lifetime, accurate detection of
      peroxynitrite in biological systems is a challenge task. In the last decade, huge
      efforts have been made to develop reliable techniques to assess the generation of
      peroxynitrite in various cellular and animal experiments. There are three major
      approaches for peroxynitrite detection, including electrochemical sensors,
      detection of nitrotyrosine formation, and fluorescent probes. Particularly,
      progress has been made in developing novel fluorescent probes to detect
      peroxynitrite with relatively high sensitivity and specificity. Herein, we review
      the recent progress made in peroxynitrite detection methods and discuss the
      advantages and disadvantages of these methods. The development of these
      techniques will offer new opportunities for understanding the roles of
      peroxynitrite in the oxidative stress-related physiological and pathological
      conditions and provide platforms for drug discovery targeting peroxynitrite and
      other free radicals for therapeutic purposes.

PMID- 24923568
TI  - Anti-cancer activities of omega-6 polyunsaturated fatty acids.
AB  - The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are two major
      families of PUFAs present as essential cellular components which possess diverse
      bioactivities. The omega-3s, mainly found in seafood, are associated with many
      beneficial effects on human health, while the omega-6s are more abundant in our
      daily diet and could be implicated in many pathological processes including
      cancer development. Increasing evidence suggests that the adverse effects of
      omega-6s may be largely attributed to arachidonic acid (AA, a downstream omega-6)
      and the metabolite prostaglandin E2 (PGE2) that stems from its cyclooxygenase
      (COX)-catalyzed lipid peroxidation. On the other hand, two of AA's upstream omega
      6s, gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DGLA), are shown
      to possess certain anti-cancer activities, including inducing cell apoptosis and
      inhibiting cell proliferation. In this paper, we review the documented anti
      cancer activities of omega-6 PUFAs, including the recent findings regarding the
      anti-cancer effects of free radical-mediated DGLA peroxidation. The possible
      mechanisms and applications of DGLA (and other omega-6s) in inducing anti-cancer
      activity are also discussed. Considering the wide availability of omega-6s in our
      daily diet, the study of the potential beneficial effect of omega-6 PUFAs may
      guide us to develop an omega-6-based diet care strategy for cancer prevention and
      treatment.

PMID- 24923570
TI  - Structural study of the microtubule-associated protein tau locus of Alzheimer's
      disease in Taiwan.
AB  - BACKGROUND: Haplotype structure of the microtubule-associated protein tau (MAPT)
      gene is associated with various tauopathies in the Caucasian population. With the
      knowledge that the association between MAPT structure and disease may be distinct
      in different ethnics, we intend to investigate the haplotype structure of MAPT in
      Taiwanese and test it for association with Alzheimer's disease (AD). METHODS: One
      hundred and eight AD patients and 108 sex- and-age matched healthy controls were
      recruited from the dementia outpatient clinic of Chang Gung Medical center. We
      genotyped the del-In9 marker that defines the extended H1 and H2 clades. We
      selected 21 single-nucleotide polymorphisms (SNPs) in the extended MAPT region
      from Japanese SNPs database and dbSNP database. Using the software TagIt, we
      analyzed the linkage disequilibrium structure of MAPT and compared the allele and
      genotype distribution between patient group and control group. RESULTS: All the
      Taiwanese participants were H1 haplotypes. Linkage disequilibrium analysis showed
      the haplotype blocks in Taiwanese population had a smaller size in comparison to
      that of the Caucasian population. Single locus association showed significant p
      value in one of the tagging variants (rs242557) in our Taiwanese AD case-control
      cohorts. CONCLUSION: MAPT gene has four haplotype blocks in the Taiwanese
      population, each of around 40 kbp. In both European study and our study, the SNP
      rs242557 showed association with AD. Given the position of this SNP, the most
      possible explanation is that genetic variability in tau expression contributes to
      the risk of developing AD.

PMID- 24923571
TI  - Concurrent chemoradiotherapy using cisplatin, tegafur, and leucovorin for
      advanced squamous cell carcinoma of the hypopharynx and oropharynx.
AB  - BACKGROUND: To evaluate the efficacy and adverse events of cisplatin, tegafur,
      and leucovorin concomitantly with radiotherapy for patients with advanced, non
      metastatic squamous cell carcinoma (SCC) of the oropharynx and hypopharynx.
      METHODS: The PTL regimen consisted of cisplatin (P) 50 mg/m 2 on day 1, oral
      tegafur (T) 800 mg/day plus leucovorin (LV) 60 mg/day on days 1 through 14. It
      was repeated every 2 weeks through the radiotherapy course. Conventional
      radiotherapy with 1.8-2.0 Gy/day, 5 days per week, was delivered in a total dose
      of between 70 and 72 Gy. RESULTS: Sixty-five patients with stage III or IV of SCC
      of the head and neck were consecutively treated between May 2002 and November
      2005. Forty-six (70.7%) patients had complete response after concomitant
      chemoradiotherapy (CCRT). With a median follow-up of 54.0 months (range 1-103
      months), the 5-year locoregional control, progression-free survival, and overall
      survival rates were 50.6%, 40.7%, and 59.7%, respectively. Three (4.6%) patients
      had toxic death during treatment. Fifty-one (80.0%) patients experienced grade 3
      4 mucositis which occurred in about 35% of the CCRT duration. The functional
      preservation rate among post-CCRT complete responders was 93.5% (43/46). The
      median cisplatin accumulated dosage was 150 mg, and the rate of hearing
      impairment among the survivors was 7.8%. CONCLUSION: CCRT with outpatient-based
      PTL for advanced SCC of oropharynx and hypopharynx is feasible and has
      comparative efficacy and acceptable adverse events.

PMID- 24923572
TI  - Modified biweekly oxaliplatin and capecitabine for advanced gastric cancer: a
      retrospective analysis from a medical center.
AB  - BACKGROUND: We modified 3-week XELOX regimen with oxaliplatin to 85 mg/m 2 on Day
      1 and capecitabine 1000 mg/m 2 BID for 10 days every 14 days to be more practical
      in clinical practice for advanced gastric cancer. The aim of this retrospective
      analysis is to evaluate the safety profile and efficacy of the modified
      oxaliplatin plus capecitabine (XELOX) regimen as the first-line treatment for
      patients with advanced gastric cancer in a medical center in Taiwan. METHODS:
      From March 2009 to December 2010, among the 614 patients diagnosed with gastric
      cancer in a medical center, 49 patients with unresectable advanced or metastatic
      gastric adenocarcinoma were treated with oxaliplatin (85 mg/m 2 ) on Day 1 and
      capecitabine (1000 mg/m 2 BID) for 10 days every 2 weeks (mXELOX). CT scan was
      performed for tumor response evaluation. Clinical outcome and adverse events
      after mXELOX treatment were analyzed retrospectively. RESULTS: A total of 354
      mXELOX sessions (median: 6) were administered in 49 patients. The overall tumor
      response rate was 39.1% among 46 evaluated patients: three complete response
      (6.5%) and 15 partial response (32.6%). Seven patients had stable disease (15.2%)
      and 21 (45.7%) patients had progressive disease. The median progression-free
      survival and median overall survival were 4.37 months and 12.26 months,
      respectively. The most common grade III/IV hematologic toxicity was anemia
      (10.2%), and non-hematologic toxicity effects were numbness (8.2%), hand-foot
      syndrome (10.2%), diarrhea (6.1%), thrombocytopenia (6.1%), and abdominal pain
      (6.1%). CONCLUSION: This modified biweekly oxaliplatin and capecitabine
      combination chemotherapy is practical and effective for unresectable advanced or
      metastatic gastric cancer in our daily practice.

PMID- 24923573
TI  - A novel and effective acupuncture modality as a complementary therapy to acute
      pain relief in inpatients with rib fractures.
AB  - BACKGROUND: Pain control has been emphasized as a priority for both practitioners
      and inpatients with rib fractures, since analgesia could only offer limited
      relief from severe pain. A prospective and randomized controlled trial was
      conducted to analyze the efficacy and efficiency of acupuncture in acute pain
      relief for inpatients with rib fractures. METHODS: A total of 58 inpatients were
      recruited and allocated to two groups, receiving identical doses of conventional
      oral analgesics as well as filiform needles as treatment and thumbtack
      intradermal (TI) needles placed upon the skin surface as a control, respectively,
      via novel acupuncture modality once daily for three consecutive days. The effect
      of pain relief was evaluated during activities that induce pain, and sustained
      maximal inspiration (SMI) lung volumes and sleep quality were assessed. RESULTS:
      The patients treated with filiform needles had more effective pain relief than
      those in the TI needle group during deep breathing, coughing, and turning over
      the body (p < 0.05), and the effect persisted for at least 6 h in most patients.
      Sustained maximal inspiration lung volumes and sleep quality did not show
      improvement through every acupuncture intervention, and they could not respond
      accurately to pain relief via acupuncture. CONCLUSION: The active evaluation
      could provide a more adaptive model for assessing pain intensity due to rib
      fractures. This novel acupuncture modality in which the needle insertion sites
      are corresponding to the pain spots can be a safe and viable therapy for
      relieving pain in inpatients with rib fractures.

PMID- 24923574
TI  - Comparison of patient's satisfaction with implant-supported mandibular
      overdentures and complete dentures.
AB  - BACKGROUND: The purpose of this study was to compare patients' subjective
      experiences with respect to long-term satisfaction with mandibular implant
      retained overdentures versus conventional complete dentures. METHODS: Among 85
      completely edentulous patients, 60 were treated with four one-stage titanium
      implants and overdentures retained by a cast bar with extracoronal attachments.
      These patients constituted the experimental group, and were subsequently
      evaluated clinically over a period of up to 6 years. The other 25 patients
      constituted the control group and were treated with conventional complete
      dentures without implant retained. All the patients (n = 60) in the experimental
      group responded to questions on their experiences before and after treatment with
      the implant-retained overdentures. Sixty percent (n = 15) of the 25 patients in
      the control group responded to the questionnaire. RESULTS: No implants or
      restorations failed during the observation period. The experimental group,
      however, showed significant differences with the control group in terms of their
      responses to the questionnaire. CONCLUSION: The use of implants to retain and
      support the overdenture improved comfort and gave the experimental patients
      greater self-confidence in social interactions, in addition to more effective
      oral rehabilitation. The results demonstrate that the effects of rehabilitation
      of the mandibular arch with an implant-retained overdenture are predictable.

PMID- 24923575
TI  - Pros and cons of the proteomics.
AB  - The number of proteins produced by the 30,000-40,000 genes of the human genome is
      estimated to be three or four orders of magnitude higher. Proteomics is a rapidly
      developing science. In principle, two main areas in the field of proteomics have
      been developed, each of them having its pros and cons. These fields are profiling
      and functional proteomics. The aim of the proteomic profiling is to describe and
      index the whole set of proteins of a biological sample, which could be an
      organism, an organ, or a cell, or parts there of like individual's tissue or
      organelles. In our understanding, both types of proteomics (profiling and
      functional) are valuable tools complementing other biological methodologies. 

PMID- 24923576
TI  - Nox1 upregulates the function of vascular T-type calcium channels following
      chronic nitric oxide deficit.
AB  - Cardiovascular disease is characterised by reduced nitric oxide bioavailability
      resulting from oxidative stress. Our previous studies have shown that nitric
      oxide deficit per se increases the contribution of T-type calcium channels to
      vascular tone through increased superoxide from NADPH oxidase (Nox). The aim of
      the present study was therefore to identify the Nox isoform responsible for
      modulating T-type channel function, as T-type channels are implicated in several
      pathophysiological conditions involving oxidative stress. We evaluated T-channel
      function in skeletal muscle arterioles in vivo, using a novel T-channel blocker,
      TTA-A2 (3 MUmol/L), which demonstrated no cross reactivity with L-type channels.
      Wild-type and Nox2 knockout (Nox2ko) mice were treated with the nitric oxide
      synthase inhibitor L-NAME (40 mg/kg/day) for 2 weeks. L-NAME treatment
      significantly increased systolic blood pressure and the contribution of T-type
      calcium channels to arteriolar tone in wild-type mice, and this was not prevented
      by Nox2 deletion. In Nox2ko mice, pharmacological inhibition of Nox1 (10 MUmol/L
      ML171), Nox4 (10 MUmol/L VAS2870) and Nox4-derived hydrogen peroxide (500 U/mL
      catalase) significantly reduced the effect of chronic nitric oxide inhibition on
      T-type channel function. In contrast, in wild-type mice, ML171 and VAS2870, but
      not catalase, reduced the contribution of T-type channels to vascular tone,
      suggesting a role for Nox1 and non-selective actions of VAS2870. We conclude that
      Nox1, but not Nox2 or Nox4, is responsible for the upregulation of T-type calcium
      channels elicited by chronic nitric oxide deficit. These data point to an
      important role for this isoform in increasing T-type channel function during
      oxidative stress.

PMID- 24923578
TI  - Left atrial volume and adverse cardiovascular outcomes in unselected patients
      with and without CKD.
AB  - BACKGROUND AND OBJECTIVES: Patients with CKD have increased cardiovascular
      morbidity and mortality. This study investigated the prognostic value of common
      clinical echocardiographic parameters. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: There were 289 unselected consecutive patients who had a
      transthoracic echocardiogram between January and June 2003. Patients with stage 3
      or 4 CKD (n=49) were compared with those with eGFR>=60 ml/min per 1.73 m(2),
      n=240). Left ventricular volume, ejection fraction and mass, left atrial volume,
      and function parameters were measured. The primary endpoint, determined a priori,
      was a composite of cardiac death, myocardial infarction, and congestive cardiac
      failure. RESULTS: Patients were followed for a median 5.6 years. The incidence of
      the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001),
      who were older and had a higher prevalence of hypertension and ischemic heart
      disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were
      higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m(2) had
      significantly lower event-free survival than patients with normal (<28 ml/m(2))
      or mildly dilated LAVI (28-32 ml/m(2)) (P<0.001). Multivariate analysis showed
      that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31;
      P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently
      associated with LAVI>32 ml/m(2). Multivariate Cox regression analysis
      demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04),
      hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR,
      1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary
      endpoint. CONCLUSIONS: Patients with CKD were at higher risk for cardiovascular
      events. LAVI was significantly larger in the CKD group and was a predictor of
      adverse cardiac events.

PMID- 24923577
TI  - Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in
      elderly men.
AB  - BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as
      a clinically relevant highly specific biomarker of acute kidney tubular damage.
      However, community-based data on the association between urinary levels of KIM-1
      and the risk for cardiovascular mortality are lacking. This study aimed to
      investigate the association between urinary KIM-1 and cardiovascular mortality.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study,
      using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean
      age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of
      follow-up, 2008). RESULTS: During follow-up, 89 participants died of
      cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models
      were adjusted for cardiovascular risk factors (age, systolic BP, diabetes,
      smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive
      treatment, lipid-lowering treatment, aspirin treatment, and history of
      cardiovascular disease) and for markers of kidney dysfunction and damage
      (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM
      1/creatinine (from 24-hour urine collections) was associated with a higher risk
      for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence
      interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high
      KIM-1/creatinine (upper quintile, >=175 ng/mmol), low eGFR (<=60 ml/min per 1.73
      m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio>=3 g/mol)
      had a >8-fold increased risk compared with participants with low KIM-1/creatinine
      (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria
      (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56;
      P<0.001). CONCLUSIONS: These findings suggest that higher urinary KIM-1 may
      predispose to a higher risk of cardiovascular mortality independently of
      established cardiovascular risk factors, eGFR, and albuminuria. Additional
      studies are needed to further assess the utility of measuring KIM-1 in the
      clinical setting.

PMID- 24923579
TI  - Potential influence of invisible coronary collateral circulation on fractional
      flow reserve of donor artery in the presence of severe stenosis of receiving
      artery.
AB  - We reported a case of 78-year-old male who had a severe stenosis in the right
      coronary artery (RCA) and an intermediate stenosis in the left anterior
      descending artery (LAD) without visible collateral flow to the RCA on angiogram.
      Fractional flow reserve (FFR) in the LAD lesion, which revealed significant value
      as 0.70, increased to 0.78 after revascularization of the RCA lesion. The FFR in
      an intermediate stenosis should be performed after PCI for severe stenosis in the
      other coronary arteries. Otherwise, the severity of the stenosis could be
      overestimated due to the presence of invisible collateral circulation. 

PMID- 24923580
TI  - A tetraphenylethene-based caged compound: synthesis, properties and applications.
AB  - A tetraphenylethene-based caged compound (TPE-C) is designed and synthesized. TPE
      C is non-fluorescent either in solution or in aggregated state, but its emission
      can be induced to emit strong cyan emission in the aggregated state by UV
      irradiation. This property enables TPE-C to be applied in photo-patterning and
      anti-counterfeiting related areas. 

PMID- 24923581
TI  - What's new in status epilepticus?

PMID- 24923582
TI  - Practical, modular, and general synthesis of benzofurans through extended
      Pummerer annulation/cross-coupling strategy.
AB  - Operationally simple, efficient, and widely applicable Pummerer annulations of
      simple phenols with ketene dithioacetal monoxides, with the aid of
      trifluoroacetic anhydride, have been shown to provide a variety of benzofurans
      having a methylthio group at the 2-position. Subsequent and newly developed
      nickel-catalyzed arylation at the methylthio group culminates in diversity
      oriented synthesis of multisubstituted benzofurans. Our extended Pummerer
      annulation/cross-coupling sequence is powerful enough to synthesize biologically
      active natural products as well as highly fluorescent benzofuran derivatives. 

PMID- 24923583
TI  - Shotgun proteomics analysis of proliferating STRO-1-positive human dental pulp
      cell after exposure to nacreous water-soluble matrix.
AB  - INTRODUCTION: For dental treatment, dentin regeneration is required after a tooth
      injury with dental pulp exposure. The effects of the water-soluble matrix (WSM)
      extracted from the nacreous layer of the bivalve Pinctada maxima on human dental
      pulp cells in vitro were challenging and useful for clinical application.
      MATERIAL AND METHODS: The biological activity of the STRO-1-positive human dental
      pulp cells in response to WSM compared to Dulbecco's modified Eagle medium (DMEM)
      as a normal control was monitored. The cell survival rate was analyzed by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Proteomic
      profiles among inducers and noninducers with time dependency were compared by
      using sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with
      liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). RESULTS: The human
      dental pulp cells cultured in nacreous WSM exhibited higher relative cell
      viability than those in DMEM with similar morphological appearance. Significant
      changes were found in the relative abundance of 44 proteins in cells after
      exposure to WSM for 2 weeks. They play a role in cell adhesion, cell
      proliferation, metabolic process, signal transduction, stress response,
      transcription, translation, and transport. CONCLUSION: These results indicate
      that WSM of P. maxima has the ability to induce proliferation of human dental
      pulp cells. CLINICAL RELEVANCE: This finding initiated the study to evaluate the
      suitability of nacre as biomaterial for dentistry.

PMID- 24923584
TI  - Efficacy of preoperative transcatheter arterial chemoembolization combined with
      systemic chemotherapy for treatment of unresectable hepatoblastoma in children.
AB  - PURPOSE: The purpose of this study was to evaluate, retrospectively, the clinical
      efficacy of preoperative transcatheter arterial chemoembolization (TACE) combined
      with systemic chemotherapy for unresectable hepatoblastoma. MATERIALS AND
      METHODS: Five boys and three girls (mean age 15.2 months) were treated with
      preoperative TACE combined with systemic chemotherapy for unresectable
      hepatoblastomas. Mean tumor diameter and mean alfa-fetoprotein (AFP) level were
      11.8 cm and 549,386 ng/mL, respectively. Pretreatment, the extent of disease
      (PRETEXT) was: II, 1; III, 6; IV, 1. For all patients, preoperative systemic
      chemotherapy was administered before TACE. At each TACE, carboplatin and
      adriamycin mixed with iodized oil were infused into the feeding arteries. Tumor
      response and prognosis after treatment were evaluated. RESULTS: TACE resulted in
      few Grade 1 adverse effects (AEs), without G3 or more AEs, according to CTACAE
      3.0. Mean tumor shrinkage was 60.9%, and the mean AFP decrease from initial
      levels was 94.8%. In all cases TACE combined with systemic chemotherapy enabled
      subsequent safe and complete surgical resection. After a mean follow-up of 59
      months, tumor-free survival was 75%. CONCLUSION: Preoperative TACE combined with
      systemic chemotherapy was effective in inducing surgical resectability of
      unresectable hepatoblastoma.

PMID- 24923586
TI  - Mycoinsecticides: potential and future perspective.
AB  - Crop damage and consequent loss in productivity associated with arthropod pests
      represent the most serious threats to the world economy. Different methods have
      been used in the past to control arthropod pests; however, the increase in
      incidences of resistance to pesticides, food safety concerns, and concerns
      related to environmental impact associated with the use of chemical pesticides
      have led to the recent expansion of biological control agents. Entomopathogenic
      fungi are important and promising bio-control agents for controlling arthropod
      pests. This review compiles recent information regarding the potential of
      entomopathogenic fungi used against arthropod pests, traits responsible for
      mycoinsecticide virulence, and possible ways to enhance the virulence of
      entomopathogenic fungi, in order to pave the way for the development of bio
      rational and eco-friendly arthropod pest management strategies. 

PMID- 24923585
TI  - Modification of rifamycin polyketide backbone leads to improved drug activity
      against rifampicin-resistant Mycobacterium tuberculosis.
AB  - Rifamycin B, a product of Amycolatopsis mediterranei S699, is the precursor of
      clinically used antibiotics that are effective against tuberculosis, leprosy, and
      AIDS-related mycobacterial infections. However, prolonged usage of these
      antibiotics has resulted in the emergence of rifamycin-resistant strains of
      Mycobacterium tuberculosis. As part of our effort to generate better analogs of
      rifamycin, we substituted the acyltransferase domain of module 6 of rifamycin
      polyketide synthase with that of module 2 of rapamycin polyketide synthase. The
      resulting mutants (rifAT6::rapAT2) of A. mediterranei S699 produced new rifamycin
      analogs, 24-desmethylrifamycin B and 24-desmethylrifamycin SV, which contained
      modification in the polyketide backbone. 24-Desmethylrifamycin B was then
      converted to 24-desmethylrifamycin S, whose structure was confirmed by MS, NMR,
      and X-ray crystallography. Subsequently, 24-desmethylrifamycin S was converted to
      24-desmethylrifampicin, which showed excellent antibacterial activity against
      several rifampicin-resistant M. tuberculosis strains.

PMID- 24923587
TI  - Extraction of aggrecan-peptide from cartilage by tissue autolysis.
AB  - Aggrecan is a cartilage specific proteoglycan containing chondroitin sulfate (CS)
      and keratan sulfate (KS). CS is an acidic polysaccharide having wide range of
      applications in pharmaceutical, cosmetic, and food industries. CS is extracted
      from cartilage by tissue proteolysis with an exogenous proteinase or by
      activating endogenous proteinases (autolysis) to release aggrecan-peptides from
      the tissue. This review is focused on the latter technique. Bovine nasal and
      tracheal cartilages, and broiler chicken sternum cartilage have been used for
      autolysis studies. To extract aggrecan-peptide, cartilage tissues are cut into
      small pieces, and incubated in a monovalent or divalent salt solution (e.g., 0.1
      M sodium or calcium acetate) at pH 4.5 and 37 &#176;C for 7 - 24 h. Most (~80% or
      more) of total tissue uronic acid, a constituent sugar of aggrecan, is extracted
      and released into the salt solution during incubation. Reextraction of the tissue
      residue results in release of a small amount of uronic acid. Aggrecan-peptides
      purified using anion exchange chromatography are large compounds containing CS
      and KS. On gel chromatography, they are excluded from the column of Sephacryl S
      300. Chemical composition analysis demonstrated that aggrecan-peptides from
      either bovine or chicken cartilage contain >90% CS with small amount (< 10%) of
      either KS or peptide. Patent information included production of aggrecan-peptide
      substantially free of DNA. The bovine aggrecan-peptide prepared by tissue
      autolysis has been used as a plate coating antigen in enzyme- linked
      immunosorbent assay (ELISA) to determine KS. 

PMID- 24923588
TI  - If I had $7,000,000 to spend on radiology equipment today.

PMID- 24923589
TI  - A 3 month old infant with a "strawberry" red mass on her nose.

PMID- 24923590
TI  - Hospital staff caring for tracheotomy patients need better training, enquiry
      finds.

PMID- 24923591
TI  - NHS England's chief executive sets out thinking on new models of care.

PMID- 24923592
TI  - Nearly one in 10 US residents has diabetes, CDC reports.

PMID- 24923593
TI  - Glutaminase 1 is essential for the differentiation, proliferation, and survival
      of human neural progenitor cells.
AB  - Glutaminase is the enzyme that converts glutamine into glutamate, which serves as
      a key excitatory neurotransmitter and one of the energy providers for cellular
      metabolism. Previous studies have revealed that mice lacking glutaminase 1
      (GLS1), the dominant isoform in the brain and kidney, died shortly after birth
      due to disrupted glutamatergic transmission, suggesting the critical role of GLS1
      in the physiological functions of synaptic network. However, whether GLS1
      regulates neurogenesis, a process by which neurons are generated from neural
      progenitor cells (NPCs), is unknown. Using a human NPC model, we found that both
      GLS1 isotypes, kidney-type glutaminase and glutaminase C, were upregulated during
      neuronal differentiation, which were correlated with the expression of neuronal
      marker microtubule-associated protein 2 (MAP-2). To study the functional impact
      of GLS1 on neurogenesis, we used small interference RNA targeting GLS1 and
      determined the expressions of neuronal genes by western blot, real-time
      polymerase chain reaction, and immunocytochemistry. siRNA silencing of GLS1
      significantly reduced the expression of MAP-2, indicating that GLS1 is essential
      for neurogenesis. To unravel the specific process(es) of neurogenesis being
      affected, we further studied the proliferation and survival of NPCs in vitro.
      siRNA silencing of GLS1 significantly reduced the Ki67(+) and increased the
      TUNEL(+) cells, suggesting critical roles of GLS1 for the proliferation and
      survival of NPCs. Together, these data suggest that GLS1 is critical for proper
      functions of NPCs, including neuronal differentiation, proliferation, and
      survival. 

PMID- 24923594
TI  - Quantitative assessment of susceptibility-weighted imaging processing methods.
AB  - PURPOSE: To evaluate different susceptibility-weighted imaging (SWI) phase
      processing methods and parameter selection, thereby improving understanding of
      potential artifacts, as well as facilitating choice of methodology in clinical
      settings. MATERIALS AND METHODS: Two major phase processing methods, homodyne
      filtering and phase unwrapping-high pass (HP) filtering, were investigated with
      various phase unwrapping approaches, filter sizes, and filter types. Magnitude
      and phase images were acquired from a healthy subject and brain injury patients
      on a 3T clinical Siemens MRI system. The results were evaluated based on image
      contrast-to-noise ratio and presence of processing artifacts. RESULTS: When using
      a relatively small filter size (32 pixels for the matrix size 512 * 512 pixels),
      all homodyne-filtering methods were subject to phase errors leading to 2% to 3%
      masked brain area in lower and middle axial slices. All phase unwrapping
      filtering/smoothing approaches demonstrated fewer phase errors and artifacts
      compared to the homodyne-filtering approaches. For performing phase unwrapping,
      Fourier-based methods, although less accurate, were 2-4 orders of magnitude
      faster than the PRELUDE, Goldstein, and Quality-guide methods. CONCLUSION:
      Although homodyne-filtering approaches are faster and more straightforward, phase
      unwrapping followed by HP filtering approaches perform more accurately in a wider
      variety of acquisition scenarios.

PMID- 24923595
TI  - Risk factors for perihilar cholangiocarcinoma: a hospital-based case-control
      study.
AB  - BACKGROUND & AIMS: Perihilar cholangiocarcinoma (pCCA) is the most common form of
      bile duct cancer, arising from cholangiocytes at the confluence of hepatic ducts.
      Given the diversity of cholangiocarcinoma (CCA) aetiology according to the
      location, and the scarcity of studies on the aetiology of pCCA, we aimed to
      identify the risk factors for pCCA. METHODS: A total of 81 patients diagnosed
      with pCCA between July 2007 and December 2013, and 162 controls matched 2:1 for
      age, sex and date of diagnosis were included in this hospital-based case-control
      study. Potential risk factors were retrospectively investigated through clinical
      records, and the associations with pCCA were studied by calculating the odds
      ratios (ORs) using conditional logistic regression analysis. RESULTS: In the
      univariate model, the prevalence of choledocholithiasis (OR: 14.00, P = 0.014),
      hepatolithiasis (OR: 12.00, P = 0.021) and diabetes mellitus (DM) (OR: 2.74, P =
      0.005) was higher in pCCA patients than in controls. Heavy smoking and cirrhosis
      were marginally significant risk factors for pCCA (P < 0.1). Multivariate
      analysis revealed an association between pCCA and hepatolithiasis,
      choledocholithiasis, DM, and heavy smoking, each, with adjusted ORs of 16.47,
      9.39, 3.36 and 2.52 respectively. DM, heavy smoking, hepatolithiasis and
      choledocholithiasis accounted for about 22.5%, 17.1%, 8.5% and 4.8% of pCCA risk
      respectively (population attributable risk percentage). CONCLUSION: Our data
      showed that DM, heavy smoking, choledocholithiasis and hepatolithiasis were risk
      factors for pCCA development, implying that pCCA may share some aetiological
      factors with intrahepatic CCA although it has been classified as extrahepatic
      CCA.

PMID- 24923596
TI  - Frequency of coeliac disease in children with breath-holding spells.
AB  - AIM: Iron deficiency anaemia (IDA), which is reported very commonly among
      patients with breath holding spells (BHS), is the most common presentation of
      coeliac disease (CD). In that aspect, IDA may be a common pathway linking these
      two diseases. The aim of this study was to evaluate the frequency of CD in
      patients with BHS. METHODS: We studied 348 children with BHS, and 470 age- and
      sex-matched controls with no known disease. Serological screening for CD was
      performed in all patients by searching for serum tissue transglutaminase
      immunoglobulin A. RESULTS: The first group consisted of 348 children with BHS
      (231 males, 117 females; mean age 2.23 +/- 1.84 years), and the second group
      consisted of 470 healthy children (284 males, 186 females; mean age 2.11 +/- 1.98
      years). A total of 300 (86.2%) patients had cyanotic type of BHS only, 27 (7.8%)
      had pallid type of BHS only and 21 (6%) had mixed type of BHS. The prevalence of
      IDA was statistically significantly higher in BHS patients compared with
      controls. Tissue transglutaminase immunoglobulin A was not detected as positive
      in any patients in either group; therefore, endoscopic and histopathological
      examinations were not performed. CONCLUSIONS: Our report is the first to describe
      the frequency of tissue transglutaminase immunoglobulin A positivity in patients
      with BHS. There was no evidence of a relationship between CD and BHS, but IDA
      seems to be an important risk factor in the development of BHS. Therefore,
      serological screening for CD in patients with BHS does not seem to be necessary.

PMID- 24923597
TI  - A stable polyaniline-benzoquinone-hydroquinone supercapacitor.
AB  - A Polyaniline-Supercapacitor with quinone electrolytes remains stable over 50 000
      galvanostatic charge-discharge cycles. The quinones provide superior stability by
      preventing the conversion of porous polyaniline to a highly reactive state. Our
      work shows that highly stable polymer-supercapacitors can be engineered by
      combining electrochemically active polymers and redox-active electrolytes with
      concerted electrochemical properties. 

PMID- 24923599
TI  - The Pinch Rhytidectomy: A Safe, Effective, "Low SMAS" Variation on the Theme.
AB  - BACKGROUND: The competitive efficacy of the superficial musculoaponeurotic system
      (SMAS) rhytidectomy (SMASectomy) facelift has been well established. However, the
      outcomes after an associated open necklift have not been as reliable; the
      persistent incidence of recurrent bands and iatrogenic deformities has prompted a
      change in technique. OBJECTIVES: The author conducted a long-term retrospective
      review to evaluate a variation on the SMASectomy facelift technique. A solely
      lateral, "low SMAS" approach was substituted for direct necklift in all patients.
      METHODS: Patients who were candidates for a facelift underwent this laterally
      based, SMASectomy technique. Those who underwent concomitant full-face CO2 laser
      resurfacing were excluded from the review. A total of 198 patients treated
      consecutively during a 7-year period (2006-2012) were included in the study.
      RESULTS: Postoperative follow-up ranged from 1 to 7 years. All patients' neck
      deformities were fully corrected by the solely lateral SMASectomy technique. In
      addition, the patients recovered more rapidly than with traditional direct
      necklift, with no nerve injuries, skin compromise, or hypertrophic scarring.
      CONCLUSIONS: Results indicate that midline open necklift can be replaced by the
      low SMASectomy. LEVEL OF EVIDENCE: 4.

PMID- 24923598
TI  - Serum mitochondrial biomarkers and damage-associated molecular patterns are
      higher in acetaminophen overdose patients with poor outcome.
AB  - Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF).
      Numerous studies have shown that APAP hepatotoxicity in mice involves
      mitochondrial dysfunction, and recent data suggest that this is also the case in
      humans. We have previously shown that glutamate dehydrogenase (GDH),
      mitochondrial DNA (mtDNA), and nuclear DNA (nDNA) fragments can be measured in
      circulation of overdose patients as mechanistic biomarkers of mitochondrial
      damage and damage-associated molecular patterns. In the present study, our aim
      was to determine whether these biomarkers are higher in serum from nonsurvivors
      of APAP-induced ALF (AALF), compared to survivors. GDH, mtDNA, and nDNA fragments
      were measured in serum from AALF patients who did (n = 34) or did not (n = 35)
      recover. Importantly, all three were significantly increased in patients who
      died, compared to those who survived (GDH: 450 +/- 73 vs. 930 +/- 145 U/L; mtDNA:
      21 +/- 6 vs. 48 +/- 13 and 33 +/- 10 vs. 43 +/- 7 ng/mL for two different genes;
      nDNA fragments: 148 +/- 13 vs. 210 +/- 13% of control). Receiver operating
      characteristic (ROC) curve analyses revealed that nDNA fragments, GDH, and mtDNA
      were predictive of outcome (area under the curve [AUC], study admission: 0.73,
      0.70, and 0.71 or 0.76, respectively, P < 0.05; AUC, time of peak ALT: 0.78,
      0.71, and 0.71 or 0.76, respectively, P < 0.05), and the results were similar to
      those from the Model for End-Stage Liver Disease (MELD; AUC, peak MELD: 0.77; P <
      0.05). CONCLUSIONS: Our data suggest that patients with more mitochondrial damage
      are less likely to survive, demonstrating that mitochondria are central in the
      mechanisms of APAP hepatotoxicity in humans. Clinically, serum nDNA fragments,
      GDH, and mtDNA could be useful as part of a panel of biomarkers to predict
      patient outcome. (Hepatology 2014;60:1336-1345).

PMID- 24923600
TI  - Does Cryolipolysis Lead to Skin Tightening? A First Report of Cryodermadstringo.

PMID- 24923601
TI  - Clarification about occurrence of complications during liposuction.

PMID- 24923603
TI  - Inappropriate antidiuretic hormone syndrome presenting as ectopic antidiuretic
      hormone-secreting gastric adenocarcinoma: a case report.
AB  - INTRODUCTION: Although the syndrome of inappropriate antidiuretic hormone has
      connection with various malignant tumors, there are few reports associated with
      advanced gastric cancer. CASE PRESENTATION: We describe the case of a 63-year-old
      Korean male with inappropriate antidiuretic hormone syndrome due to an ectopic
      antidiuretic hormone-producing advanced gastric adenocarcinoma manifested with
      overt serum hypo-osmolar hyponatremia and high urinary sodium concentrations. His
      adrenal, thyroidal, and renal functioning were normal, and the hyponatremia
      improved following removal of the tumor. The cancer cells were immunostained and
      found to be positive for the antidiuretic hormone. To our knowledge, this is the
      first report of an antidiuretic hormone-secreting advanced gastric adenocarcinoma
      associated with the syndrome of inappropriate antidiuretic hormone, showing
      cancer cells immunostained for the antidiuretic hormone. CONCLUSIONS: Although a
      strong relationship between gastric cancer and the syndrome of inappropriate
      antidiuretic hormone remains to be established, we suggest that gastric cancer
      could be included as a differential diagnosis of cancer that is associated with
      the syndrome of antidiuretic hormone.

PMID- 24923604
TI  - Interaction between pre-weaning undernutrition and post-weaning environmental
      enrichment on somatic development and behaviour in male and female rats.
AB  - Male and female rats were undernourished from birth to 30 days by restricting
      access to the lactating mother, and then fed ad libitum. At weaning, underfed and
      normally suckled controls were permanently housed either in pairs in standard
      cages or in groups of 10 in 1 m(3) cages containing ladders, ropes etc. Severe
      undernutrition during suckling followed by 4 months of refeeding, produced some
      changes in sexual behaviour in adult males (increased ejaculation frequency) but
      had no effect on behaviour in open field, dark preference or passive avoidance.
      Differential post-weaning environment produced significant differences in
      behaviour, irrespective of previous feeding conditions. Enriched animals were
      more active and exploratory. Females differed from males in the same direction as
      enriched from standard, and were more responsive to social and housing
      conditions. 

PMID- 24923605
TI  - Intermale aggression of subordinate resident long-evans rats.
AB  - Dominant male rats were separated from their colonies and subordinate residents
      were tested for aggression after a two week period. Subordinate animals showed
      significant increases in body weight and aggressive behavior toward intruders.
      Replacement of the previously dominant male led to rank reversals in three of six
      colonies. To assess whether two weeks of separation from the dominant male was
      necessary for subordinate males to exhibit aggression towards conspecifics,
      another intruder test was given following an additional two weeks of social
      housing. At the conclusion of this test, the more aggressive resident was removed
      and a naive intruder was immediately introduced into the colony with the
      subordinate male resident and again at 1, 5, and 10 day intervals. Aggressive
      posturing by the subordinate resident increased immediately following the removal
      of the dominant male, and remained at a high level throughout the subsequent
      intruder tests. In contrast, biting was initially low but increased steadily
      throughout the period of separation. These findings demonstrated that social or
      situational changes within a colony can greatly influence the aggression of
      subordinate males. 

PMID- 24923602
TI  - Salicylic acid signaling controls the maturation and localization of the
      arabidopsis defense protein ACCELERATED CELL DEATH6.
AB  - ACCELERATED CELL DEATH6 (ACD6) is a multipass membrane protein with an ankyrin
      domain that acts in a positive feedback loop with the defense signal salicylic
      acid (SA). This study implemented biochemical approaches to infer changes in ACD6
      complexes and localization. In addition to forming endoplasmic reticulum (ER)-
      and plasma membrane (PM)-localized complexes, ACD6 forms soluble complexes, where
      it is bound to cytosolic HSP70, ubiquitinated, and degraded via the proteasome.
      Thus, ACD6 constitutively undergoes ER-associated degradation. During SA
      signaling, the soluble ACD6 pool decreases, whereas the PM pool increases.
      Similarly, ACD6-1, an activated version of ACD6 that induces SA, is present at
      low levels in the soluble fraction and high levels in the PM. However, ACD6
      variants with amino acid substitutions in the ankyrin domain form aberrant,
      inactive complexes, are induced by a SA agonist, but show no PM localization. SA
      signaling also increases the PM pools of FLAGELLIN SENSING2 (FLS2) and BRI1
      ASSOCIATED RECEPTOR KINASE 1 (BAK1). FLS2 forms complexes ACD6; both FLS2 and
      BAK1 require ACD6 for maximal accumulation at the PM in response to SA signaling.
      A plausible scenario is that SA increases the efficiency of productive folding
      and/or complex formation in the ER, such that ACD6, together with FLS2 and BAK1,
      reaches the cell surface to more effectively promote immune responses. 

PMID- 24923606
TI  - Effects of varied prior manipulatory or consummatory behaviours on nut opening,
      predation, novel foods consumption, nest building, and food tablet grasping in
      rats.
AB  - Varied manipulatory-gnawing experience with nonfood objects facilitated later nut
      opening and insect predation in rats. Varied food consumption, which minimized
      manipulation, facilitated the hulling and consumption of sunflower seeds. Both
      treatments weakly facilitated forepaw food tablet grasping but neither treatment
      altered novel foods consumption or nest building. The data suggest that these two
      forms of prior experience contribute differentially to some later behaviours
      depending upon the sensory-motoric demands of the task and/or upon the intensity
      of food related stimulation. 

PMID- 24923607
TI  - Effects of residence, aggressive experience and intruder familiarity on attack
      shown by male mice.
AB  - Two groups of 12 mature male Swiss Morini strain mice were matched for
      aggressiveness on the basis of their response to anosmic docile male intruders
      after 24 h individual housing in a large defensible cage. One group was
      subsequently individually housed without disturbance for a further 12 days
      whereas the second group was exposed to a new anosmic intruder every 3 days over
      this same period. All mice were subsequently retested against anosmic intruders
      for a 10 min period. Animals which had had the opportunity to fight repeatedly
      showed more attack than individuals lacking such experience. A second experiment
      contrasted the responses of dominant isolates to the same or a different anosmic
      intruder, 10 min after a successful attack. Familiar intruders were attacked less
      vigorously than unfamiliar mice. It seems likely that the defeated mouse becomes
      less potent as a stimulus eliciting attack as the resident becomes habituated to
      it. Conversely, unfamiliar intruders evoke aggressive reactions by residents
      despite the prolonged fights they had had before final testing. These experiments
      provide little support for the appetence view of aggression in mice (i.e. the
      view that aggressiveness is augmented by depriving the animal of the opportunity
      to fight) or the view that this phenomenon is simply a consequence of "social
      deprivation". 

PMID- 24923608
TI  - Suppression of reproductive maturation in male-stimulated virgin female microtus
      by a female urinary chemosignal.
AB  - Urine from female Microtus ochrogaster possesses a chemosignal that suppresses
      reproductive maturation in other females. Uterine enlargement in virgin females
      stimulated by a male was suppressed by subsequent association with another female
      or by application of female urine on the nose. Females so suppressed are not able
      to achieve estrus. Urine from virgin sibling and non-sibling females and from
      pregnant females possesses the suppressing effect. 

PMID- 24923609
TI  - Neonate orientation towards human voice differs with type of feeding.
AB  - Within the first day after birth, infants develop the tendency to respond to
      human voices with enhanced asymmetrical mouthing. Breast-fed infants generally
      mouthed in the same direction as the voice while bottle-fed infants usually
      mouthed towards the left, wherever the voice came from. In both groups, this
      response thus reflects the orientation of anticipatory mouthing in the feeding
      situation. 

PMID- 24923610
TI  - Ontogenese de certains aspects de l'orientation du grillon des bois Nemobius
      sylvestris (Bosc), dans son milieu naturel.
AB  - The ontogeny of the orientation of the wood-cricket, Nemobius sylvestris, was
      studied experimentally in a variety of biotopes. In each experimental situation,
      the straightness of the routes taken by crickets improves with age. These results
      demonstrate that, depending on the variety of the constraints within each living
      area, various local individual solutions to the problem of orientation develop
      during ontogeny. 

PMID- 24923611
TI  - Cleaning behaviour of the goldsinny (Pisces, Labridae) in Swedish waters.
AB  - The goldsinny, Ctenolabrus rupestris , on the Swedish west-coast has been shown
      to be a facultative cleaner with the ballan wrasse, Labrus berggylta , as the
      cleanee. Twenty-four cleanings were observed during 1975 to 1981. The cleaning
      pattern of the symbiosis is described and the low rate of cleaners within the
      species is discussed. 

PMID- 24923612
TI  - Finite state grammars for dialects of the advertising song of the savannah
      sparrow (Passerculus Sandwichensis ).
AB  - Right-linear finite state grammars were extracted for song sequences of Savannah
      Sparrows (Passerculus sandwichensis) from Ontario and Nova Scotia. The Nova
      Scotia grammar was found to be longer than the Ontario grammar (possess more
      rewrite statements) and allow for the production of sequences containing
      consecutive trills. These differences are discussed with respect to genetic and
      environmental factors shaping song behaviour in the two regions. Limitations of a
      nonstochastic finite state grammar procedure are also addressed. 

PMID- 24923617
TI  - Instructions and format of a camera-ready paper for direct photo-offset
      reproduction.
AB  - These instructions are presented to assist you in preparing a typescript
      (Chomsky, 1977) which is suitable for direct photo-offset reproduction. Your
      manuscript (Rome and Rome, 1971) should be prepared on special paper (Freed et
      at., 1975) provided by the publisher. It will be photographically reproduced,
      whereby a reduction to 75% of its original size will be applied. 

PMID- 24923618
TI  - Meta-analysis of face processing event-related potentials in schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with impaired face processing. N170 and
      N250 are two event-related potentials that have been studied in relation to face
      processing in schizophrenia, but the results have been mixed. The aim of this
      article was to conduct a meta-analysis of N170 and N250 in schizophrenia to
      evaluate trends and resolve the inconsistencies. METHODS: Twenty-one studies of
      N170 (n = 438 schizophrenia patients, n = 418 control subjects) and six studies
      of N250 (n = 149 schizophrenia patients, n = 151 control subjects) were
      evaluated. Hedges' g was calculated for each study, and the overall weighted mean
      effect size (ES) was calculated for N170 and N250. Homogeneity of the ES
      distributions, potential publication bias, and impact of potential moderators
      were also assessed. RESULTS: The amplitude of both N170 and N250 to face stimuli
      was smaller in patients than control subjects (N170 ES = .64; N250 ES = .49; ps <
      .001). The distributions of the ES were homogeneous (ps > .90), and there was no
      indication of a publication bias. We found no significant effect of task
      requirements regarding judgments of the face stimuli. Moreover, we found no
      significant difference between the ES for N170 and N250. CONCLUSIONS: Though
      findings of individual studies have been mixed, the results of the meta-analysis
      strongly support disruption of N170 and N250 in schizophrenia. The comparable
      effect sizes across the two waveforms suggest that the well-established
      behavioral deficit in face emotion processing is mirrored in an underlying neural
      impairment for processing faces.

PMID- 24923619
TI  - Event-related potential and time-frequency endophenotypes for schizophrenia and
      psychotic bipolar disorder.
AB  - BACKGROUND: The investigators compared event-related potential (ERP) amplitudes
      and event-related oscillations across a broad frequency range during an auditory
      oddball task using a comprehensive analysis approach to describe shared and
      unique neural auditory processing characteristics among healthy subjects (HP),
      schizophrenia probands (SZ) and their first-degree relatives, and bipolar
      disorder I with psychosis probands (BDP) and their first-degree relatives.
      METHODS: This Bipolar-Schizophrenia Network on Intermediate Phenotypes sample
      consisted of clinically stable SZ (n = 229) and BDP (n = 188), HP (n = 284),
      first-degree relatives of schizophrenia probands (n = 264), and first-degree
      relatives of bipolar disorder I with psychosis probands (n = 239). They were
      administered an auditory oddball task in the electroencephalography environment.
      Principal components analysis derived data-driven frequency bands evoked power.
      Spatial principal components analysis reduced ERP and frequency data to component
      waveforms for each subject. Clusters of time bins with significant group
      differences on response magnitude were assessed for proband/relative differences
      from HP and familiality. RESULTS: Nine variables survived a linear discriminant
      analysis between HP, SZ, and BDP. Of those, two showed evidence (deficit in
      relatives and familiality) as genetic risk markers more specific to SZ (N1, P3b),
      one was specific to BDP (P2) and one for psychosis in general (N2). CONCLUSIONS:
      This study supports for both shared and unique deficits in early sensory and late
      cognitive processing across psychotic diagnostic groups. Additional ERP and time
      frequency component alterations (frontal N2/P2, late high, early, mid, and low
      frequency) may provide insight into deficits in underlying neural architecture
      and potential protective/compensatory mechanisms in unaffected relatives.

PMID- 24923620
TI  - Differentiation of calcified regions and iron deposits in the ageing brain on
      conventional structural MR images.
AB  - PURPOSE: In the human brain, minerals such as iron and calcium accumulate
      increasingly with age. They typically appear hypointense on T2*-weighted MRI
      sequences. This study aims to explore the differentiation and association between
      calcified regions and noncalcified iron deposits on clinical brain MRI in
      elderly, otherwise healthy subjects. MATERIALS AND METHODS: Mineral deposits were
      segmented on co-registered T1- and T2*-weighted sequences from 100 1.5 Tesla MRI
      datasets of community-dwelling individuals in their 70s. To differentiate
      calcified regions from noncalcified iron deposits we developed a method based on
      their appearance on T1-weighted images, which was validated with a purpose
      designed phantom. Joint T1- and T2*-weighted intensity histograms were
      constructed to measure the similarity between the calcified and noncalcified iron
      deposits using a Euclidean distance based metric. RESULTS: We found distinct
      distributions for calcified regions and noncalcified iron deposits in the
      cumulative joint T1- and T2*-weighted intensity histograms across all subjects
      (correlations ranging from 0.02 to 0.86; mean = 0.26 +/- 0.16; t = 16.93; P <
      0.001) consistent with differences in iron and calcium signal in the phantom. The
      mean volumes of affected tissue per subject for calcified and noncalcified
      deposits were 236.74 +/- 309.70 mm(3) and 283.76 +/- 581.51 mm(3); respectively.
      There was a positive association between the mineral depositions (beta = 0.32, P
      < 0.005), consistent with existing literature reports. CONCLUSION: Calcified
      mineral deposits and noncalcified iron deposits can be distinguished from each
      other by signal intensity changes on conventional 1.5T T1-weighted MRI and are
      significantly associated in brains of elderly, otherwise healthy subjects.

PMID- 24923621
TI  - The management of early osteoarthritis.

PMID- 24923622
TI  - Physical activity, weight status, diabetes and dementia: a 34-year follow-up of
      the population study of women in Gothenburg.
AB  - BACKGROUND: There is evidence of a synergistic interaction between obesity and
      sedentary lifestyle with respect to diabetes. Although diabetes is a known risk
      factor for dementia, it is unclear if both diseases have common aetiologies.
      METHODS: A community-based sample of 1,448 Swedish women, aged 38-60 years and
      free of diabetes and dementia in 1968, was followed by means of up to 5
      examinations spread over 34 years. 9.6% of all women developed diabetes and 11.4%
      developed dementia (over 40,000 person-years of follow-up for each disease). Cox
      proportional hazard regression was used to assess the influence of selected risk
      factors on both diseases, and the relation between diabetes and dementia.
      RESULTS: Comparing risk factors for incident diabetes and dementia, both diseases
      showed a synergistic association with obesity combined with a low level of
      leisure time physical activity [hazard ratio (HR) for interaction = 2.7, 95%
      confidence interval (CI) = 1.2-6.3 for diabetes and HR = 3.3, 95% CI = 1.1-9.9
      for dementia]. Development of diabetes doubled the risk for subsequent dementia
      (HR = 2.2, 95% CI = 1.1-4.4), which was slightly reduced upon adjustment for
      common risk factors. CONCLUSIONS: Shared risk factors suggest a similar aetiology
      for diabetes and dementia and partially explain the association between diseases.

PMID- 24923623
TI  - Steps toward improving diet and exercise for cancer survivors (STRIDE): a quasi
      randomised controlled trial protocol.
AB  - BACKGROUND: Cancer survivorship rates have increased in developed countries
      largely due to population ageing and improvements in cancer care. Survivorship is
      a neglected phase of cancer treatment and is often associated with adverse
      physical and psychological effects. There is a need for broadly accessible, non
      pharmacological measures that may prolong disease-free survival, reduce or
      alleviate co-morbidities and enhance quality of life. The aim of the Steps TowaRd
      Improving Diet and Exercise (STRIDE) study is to evaluate the effectiveness of an
      online-delivered physical activity intervention for increasing walking in cancer
      survivors living in metropolitan and rural areas of South Australia.
      METHODS/DESIGN: This is a quasi-randomised controlled trial. The intervention
      period is 12-weeks with 3-month follow-up. The trial will be conducted at a
      university setting and community health services in South Australia. Participants
      will be insufficiently active and aged 18 years or older. Participants will be
      randomly assigned to either the intervention or control group. All participants
      will receive a pedometer but only the intervention group will have access to the
      STRIDE website where they will report steps, affect and ratings of perceived
      exertion (RPE) during exercise daily. Researchers will use these variables to
      individualise weekly step goals to increase walking.The primary outcome measure
      is steps per day. The secondary outcomes are a) health measures (anthropometric
      and physiological), b) dietary habits (consumption of core foods and non-core
      foods) and c) quality of life (QOL) including physical, psychological and social
      wellbeing. Measures will be collected at baseline, post-intervention and 3-month
      follow-up. DISCUSSION: This protocol describes the implementation of a trial
      using an online resource to assist cancer survivors to become more physically
      active. It is an innovative tool that uses ratings of perceived exertion and
      daily affect to create individualised step goals for cancer survivors. The
      research findings may be of relevance to public health policy makers as an
      efficacious and inexpensive online-delivered intervention can have widespread
      application and may improve physical and psychological outcomes among this
      vulnerable population. Findings may indicate directions for the implementation of
      future physical activity interventions with this population. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry: ACTRN12613000473763.

PMID- 24923624
TI  - A quick, easy, cheap, effective, rugged, and safe method for the simultaneous
      detection of four triazolone herbicides in cereals combined with ultrahigh
      performance liquid chromatography with tandem mass spectrometry.
AB  - This paper describes a novel, rapid, and sensitive analytical method for
      monitoring four triazolone herbicides in cereals (wheat, rice, corn, and
      soybean), using a quick, easy, cheap, effective, rugged, and safe sample
      extraction procedure followed by ultrahigh performance liquid chromatography
      coupled with tandem mass spectrometry. The four triazolone herbicides
      (amicarbazone, carfentrazone-ethyl, sulfentrazone, and thiencarbazone-methyl)
      were extracted using acidified acetonitrile (containing 1% v/v formic acid) and
      subsequently purified with octadecylsilane (C18 ) prior to sample analysis.
      Ultrahigh performance liquid chromatography coupled with tandem mass spectrometry
      was operated in positive and negative ionization switching mode. Amicarbazone and
      carfentrazone-ethyl were detected in the positive mode (ESI+), while
      sulfentrazone and thiencarbazone-methyl were detected in the negative mode (ESI
      ). All compounds were successfully separated in less than 3.0 min. Further
      optimization achieved desired recoveries ranging from 74.5 to 102.1% for all
      analytes with relative standard deviation values <=17.2% in all tested matrices
      at three levels (10, 100, and 500 MUg/kg). The limits of detection for all
      compounds were <=2.3 MUg/kg, and the limits of quantitation did not exceed 7.1
      MUg/kg. The developed method showed excellent linearity (R(2) >= 0.994) and was
      proven to be highly efficient and reliable for the routine monitoring of
      triazolone herbicides in cereals. 

PMID- 24923625
TI  - The Relationship Between Structural Game Characteristics and Gambling Behavior: A
      Population-Level Study.
AB  - The aim of this study was to examine the relationship between the structural
      characteristics and gambling behavior among video lottery terminal (VLT)
      gamblers. The study was ecological valid, because the data consisted of actual
      gambling behavior registered in the participants natural gambling environment
      without intrusion by researchers. Online behavioral tracking data from Multix, an
      eight game video lottery terminal, were supplied by Norsk-Tipping (the state
      owned gambling company in Norway). The sample comprised the entire population of
      Multix gamblers (N = 31,109) who had gambled in January 2010. The individual
      number of bets made across games was defined as the dependent variable, reward
      characteristics of a game (i.e., payback percentage, hit frequency, size of
      winnings and size of jackpot) and bet characteristics of a game (i.e., range of
      betting options and availability of advanced betting options) served as the
      independent variables. Control variables were age and gender. Two separate cross
      classified multilevel random intercepts models were used to analyze the
      relationship between bets made, reward characteristics and bet characteristics,
      where the number of bets was nested within both individuals and within games. The
      results show that the number of bets is positively associated with payback
      percentage, hit frequency, being female and age, and negatively associated with
      size of wins and range of available betting options. In summary, the results show
      that the reward characteristics and betting options explained 27% and 15% of the
      variance in the number of bets made, respectively. It is concluded that
      structural game characteristics affect gambling behavior. Implications of
      responsible gambling are discussed.

PMID- 24923626
TI  - New autostatic surgical retractor in head and neck surgery.

PMID- 24923627
TI  - RE: De Boer EWJ, Dijkstra PU, Stegenga B, et al. Value of cone-beam computed
      tomography in the process of diagnosis and management of disorders of the
      temporomandibular joint. Br J Oral Maxillofac Surg 52;2014:241-46.

PMID- 24923628
TI  - Communication problems after the Great East Japan Earthquake of 2011.
AB  - OBJECTIVES: After the 2011 Great East Japan Earthquake, the resource utilization
      of and the problems encountered with communication devices were examined.
      METHODS: A questionnaire survey was submitted to disaster medical assistance
      teams (DMATs) that were at the primary sites of destruction after the earthquake.
      RESULTS: We collected data from 196 teams. During the first 4 days after the
      earthquake, the use of mobile phones, laptop computers, and landline phones was
      rated as poor to moderate, and satisfaction was very low, while satisfaction with
      satellite phones was rated as good to moderate (50%). The degree of satisfaction
      continued to increase gradually over time. Satellite phones, however, had several
      problems: poor reception, line instability, voice call use only, and inability to
      send large amounts of data. CONCLUSIONS: To ensure effective communication during
      the acute phase in the aftermath of large disasters, a new satellite
      communication device is needed that not only is portable, battery powered, and
      able to send large volumes of data, but also offers stable communication.

PMID- 24923629
TI  - Study on the synthesis of sulfonamide derivatives and their interaction with
      bovine serum albumin.
AB  - Three sulfonamide derivatives (SAD) were first synthesized from p-hydroxybenzoic
      acid and sulfonamides (sulfadimidine, sulfamethoxazole and sulfachloropyridazine
      sodium) and were characterized by elemental analysis, (1) H NMR and MS. The
      interaction between bovine serum albumin (BSA) and SAD was studied using UV/vis
      absorption spectroscopy, fluorescence spectroscopy, time-resolved fluorescence
      spectroscopy and circular dichroism spectra under imitated physiological
      conditions. The experimental results indicated that SAD effectively quenched the
      intrinsic fluorescence of BSA via a static quenching process. The thermodynamic
      parameters showed that hydrogen bonding and van der Waal's forces were the
      predominant intermolecular forces between BSA and two SADs [4-((4-(N-(4,6
      dimethylpyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate and 4-((4-(N-(5
      methylisoxazol-3-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate], but hydrophobic
      forces played a major role in the binding process of BSA and 4-((4-(N-(6
      chloropyridazin-3-yl)sulfamoyl)phenyl) carbamoyl)phenyl acetate. In addition, the
      effect of SAD on the conformation of BSA was investigated using synchronous
      fluorescence spectroscopy and circular dichroism spectra. Molecular modeling
      results showed that SAD was situated in subdomain IIA of BSA.

PMID- 24923630
TI  - Fluorescent-tilmanocept for tumor margin analysis in the mouse model.
AB  - BACKGROUND: Dendritic cells (DC) are localized in close proximity to cancer cells
      in many well-known tumors, and thus maybe a useful target for tumor margin
      assessment. MATERIALS AND METHODS: [(99m)Tc]- cyanine 7 (Cy7)-tilmanocept was
      synthesized and in vitro binding assays to bone marrow-derived DC were performed.
      Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma
      tumors, were administered 1.0 nmol of [(99m)Tc]-Cy7-tilmanocept via tail vein
      injection. After fluorescence imaging 1 or 2 h after injection, the tumor,
      muscle, and blood were assayed for radioactivity to calculate percent-injected
      dose. Digital images of the tumors after immunohistochemical staining for DC were
      analyzed to determine DC density. RESULTS: In vitro binding demonstrated
      subnanomolar affinity of [(99m)Tc]-Cy7-tilmanocept to DC (KA = 0.31 +/- 0.11 nM).
      After administration of [(99m)Tc]-Cy7-tilmanocept, fluorescence imaging showed a
      5.5-fold increase in tumor signal as compared with preinjection images and a 3.3
      fold difference in fluorescence activity when comparing the tumor with the
      surgical bed after tumor excision. Immunohistochemical staining analysis
      demonstrated that DC density positively correlated with tumor percent of injected
      dose per gram (r = 0.672, P = 0.03), and higher DC density was observed at the
      periphery versus center of the tumor (186 +/- 54 K versus 64 +/- 16 K arbitrary
      units, P = 0.001). CONCLUSIONS: [(99m)Tc]-Cy7-tilmanocept exhibits in vitro and
      in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting
      agent.

PMID- 24923631
TI  - Moving beyond survival as a measure of success: understanding the patient
      experience of necrotizing soft-tissue infections.
AB  - BACKGROUND: Necrotizing soft tissue infections (NSTIs) represent a devastating
      spectrum of disease with high case mortality and resource intensive care.
      Treatment consists of wide surgical debridement and often prolonged periods of
      intensive care unit care. Major complications are common. The severity of the
      disease and the aggressive treatment requirements put survivors at risk for
      significant long-term sequelae related to the trauma of both disease and
      treatment. Information about the postdischarge impact of NSTIs on survivors is
      extremely limited. Qualitative approaches are typically used to explore new
      phenomena and to capture individuals' thoughts, feelings, or interpretations of
      meaning and process. Therefore, qualitative methods are ideally suited for
      hypothesis generation to guide future quantitative study and ensure measured
      outcomes are patient-centered. MATERIALS AND METHODS: Semistructured interviews
      were conducted with survivors of NSTIs from a single regional referral center.
      Stratified purposive sampling was used to select interview candidates based on
      severity of illness. Descriptive thematic analysis was performed to identify
      major themes described by the patients. RESULTS: Interviews with 18 survivors
      identified three primary domains of experience: (1) individual factors, (2)
      relational factors, and (3) societal factors. These domains were split into the
      following two categories: factors effecting the disease process and recovery, and
      factors that were outcomes of the disease process. Each category yielded between
      one and seven themes. Themes identified included physical, psychological,
      relationship, and employment aspects. CONCLUSIONS: Patient's reported quality of
      life was significantly affected by their disease and recovery. The results
      demonstrate that many outcomes of importance for patients are not easily assessed
      by traditional measures of outcomes. This work illustrates the multidimensional
      nature of recovery from critical illness, and shows that it represents a massive
      transition period in the lives of survivors that affects the patient, their
      family, and the patient's ability to interact with society. Interviews with
      survivors ensure that the patient voice is heard before developing tools to
      assess long-term outcomes.

PMID- 24923632
TI  - Effect of physicochemical parameters on nitrile-hydrolyzing potentials of newly
      isolated nitrilase of Fusarium oxysporum f. sp. lycopercisi ED-3.
AB  - In recent years, nitrilases from fungus have received increasing attention, and
      most of the studies are performed on nitrilases of bacterial origin. Frequently
      used methods are based on analytical methods such as high-performance liquid
      chromatography, liquid chromatography-mass spectrometry, and gas chromatography;
      therefore, an efficient, user friendly, and rapid method has been developed to
      screen nitrilase enzyme based on the principle of color change of a pH indicator.
      Phenol red amended with the minimal medium appears light yellow at neutral pH,
      which changes into pink with the formation of ammonia, indicating nitrilase
      activity in the reaction medium. A highly potent strain ED-3 identified as
      Fusarium oxysporum f. sp. lycopercisi (specific activity 17.5 umol/Min/mg dcw)
      was isolated using this method. The nitrilase activity of F. oxysporum f. sp.
      lycopercisi ED-3 strain showed wide substrate specificity toward aliphatic
      nitriles, aromatic nitriles, and orthosubstituted heterocyclic nitriles. 4
      Aminobenzonitrile was found to be a superior substrate among all the nitriles
      used in this study. This nitrilase was active within pH 5-10 and temperature
      ranging from 25 to 60  degrees C with optimal at pH 7.0 and temperature at 50 
      degrees C. The nitrilase activity was enhanced to several folds through
      optimization of culture and biotransformation conditions from 1,121 to 1,941
      umol/Min.

PMID- 24923634
TI  - Grazing under experimental hypercapnia and elevated temperature does not affect
      the radula of a chiton (Mollusca, Polyplacophora, Lepidopleurida).
AB  - Chitons (class Polyplacophora) are benthic grazing molluscs with an eight-part
      aragonitic shell armature. The radula, a serial tooth ribbon that extends
      internally more than half the length of the body, is mineralised on the active
      feeding teeth with iron magnetite apparently as an adaptation to constant grazing
      on rocky substrates. As the anterior feeding teeth are eroded they are shed and
      replaced with a new row. The efficient mineralisation and function of the radula
      could hypothetically be affected by changing oceans in two ways: changes in
      seawater chemistry (pH and pCO2) may impact the biomineralisation pathway,
      potentially leading to a weaker or altered density of the feeding teeth; rising
      temperatures could increase activity levels in these ectothermic animals, and
      higher feeding rates could increase wear on the feeding teeth beyond the animals'
      ability to synthesise, mineralise, and replace radular rows. We therefore
      examined the effects of pH and temperature on growth and integrity in the radula
      of the chiton Leptochiton asellus. Our experiment implemented three temperature
      (~10, 15, 20  degrees C) and two pCO2 treatments (~400 MUatm, pH 8.0; ~2000
      MUatm, pH 7.5) for six treatment groups. Animals (n = 50) were acclimated to the
      treatment conditions for a period of 4 weeks. This is sufficient time for growth
      of ca. 7-9 new tooth rows or 20% turnover of the mineralised portion. There was
      no significant difference in the number of new (non-mineralised) teeth or total
      tooth row count in any treatment. Examination of the radulae via SEM revealed no
      differences in microwear or breakage on the feeding cusps correlating to
      treatment groups. The shell valves also showed no signs of dissolution. As a
      lineage, chitons have survived repeated shifts in Earth's climate through
      geological time, and at least their radulae may be robust to future
      perturbations.

PMID- 24923633
TI  - Daily walking and the risk of incident functional limitation in knee
      osteoarthritis: an observational study.
AB  - OBJECTIVE: Physical activity is recommended to mitigate functional limitations
      associated with knee osteoarthritis (OA). However, it is unclear whether walking
      on its own protects against the development of functional limitation. METHODS:
      Walking over 7 days was objectively measured as steps/day within a cohort of
      people with or at risk of knee OA from the Multicenter Osteoarthritis Study.
      Incident functional limitation over 2 years was defined by performance-based
      (gait speed <1.0 meter/second) and self-report (Western Ontario and McMaster
      Universities Osteoarthritis Index physical function score >28 of 68) measures. We
      evaluated the association of steps/day at baseline with developing functional
      limitation 2 years later by calculating risk ratios adjusted for potential
      confounders. The number of steps/day that best distinguished risk for developing
      functional limitation was estimated from the maximum distance from chance on
      receiver operating characteristic curves. RESULTS: Among 1,788 participants (mean
      age 67 years, mean body mass index 31 kg/m(2) , 60% women), each additional 1,000
      steps/day was associated with a 16% and 18% reduction in incident functional
      limitation by performance-based and self-report measures, respectively. Walking
      <6,000 and <5,900 steps/day were the best thresholds to distinguish incident
      functional limitation by performance-based (sensitivity 67.3%, specificity 71.8%)
      and self-report (sensitivity 58.7%, specificity 68.9%) measures, respectively.
      CONCLUSION: More walking was associated with less risk of functional limitation
      over 2 years. Walking >6,000 steps/day provides a preliminary estimate of the
      level of walking activity to protect against developing functional limitation in
      people with or at risk of knee OA.

PMID- 24923635
TI  - Lessons learned during the development and transfer of technology related to a
      new Hib conjugate vaccine to emerging vaccine manufacturers.
AB  - The incidence of Haemophilus Influenzae type b (Hib) disease in developed
      countries has decreased since the introduction of Hib conjugate vaccines in their
      National Immunization Programs (NIP). In countries where Hib vaccination is not
      applied routinely, due to limited availability and high cost of the vaccines,
      invasive Hib disease is still a cause of mortality. Through the development of a
      production process for a Hib conjugate vaccine and related quality control tests
      and the transfer of this technology to emerging vaccine manufacturers in
      developing countries, a substantial contribution was made to the availability and
      affordability of Hib conjugate vaccines in these countries. Technology transfer
      is considered to be one of the fastest ways to get access to the technology
      needed for the production of vaccines. The first Hib conjugate vaccine based on
      the transferred technology was licensed in 2007, since then more Hib vaccines
      based on this technology were licensed. This paper describes the successful
      development and transfer of Hib conjugate vaccine technology to vaccine
      manufacturers in India, China and Indonesia. By describing the lessons learned in
      this process, it is hoped that other technology transfer projects can benefit
      from the knowledge and experience gained. 

PMID- 24923636
TI  - Better vaccines for healthier life. Part I. Conference report of the DCVMN
      International 14th Annual General Meeting Hanoi, Vietnam.
AB  - The Developing Countries Vaccine Manufacturers' Network (DCVMN) brought together
      nearly 220 senior representatives of governmental and non-governmental global
      health organizations, as well as corporate executives of emerging vaccine
      manufacturers, from 26 countries for a two-day tailored lectures, Q&A sessions,
      CEOs panel discussion and networking opportunities, followed by a vaccine
      technology symposium and visit to manufacturing facilities in Hanoi, Vietnam.
      Participants included representatives of 38 vaccine manufacturers, as well as
      international partners and collaborating research institutions, with 39% female
      participants. The Vice-Minister of Health to Vietnam commended the speakers and
      participants to this Annual General Meeting, devoted to achieve our common goal
      of protecting people against infectious diseases with better vaccines, for a
      healthier life. He reminded the audience that the first vaccine produced in
      Vietnam was oral polio vaccine (OPV) in the early 1960s and contributed to polio
      eradication in Vietnam, in 2000. Through its manufacturing resources, Vietnam
      eliminated neonatal tetanus in 2005, and has controlled measles and hepatitis B
      spread. The Ministry of Health hopes that by sharing experiences, delegates at
      this conference will foster international cooperation and partnerships among
      organizations. CEOs elaborated on challenges and opportunities for emerging
      countries. 

PMID- 24923637
TI  - Tobacco mosaic virus efficiently targets DC uptake, activation and antigen
      specific T cell responses in vivo.
AB  - Over the past 20 years, dendritic cells (DCs) have been utilized to activate
      immune responses capable of eliminating cancer cells. Currently, ex vivo DC
      priming has been the mainstay of DC cancer immunotherapies. However, cell-based
      treatment modalities are inherently flawed due to a lack of standardization,
      specialized facilities and personnel, and cost. Therefore, direct modes of DC
      manipulation, circumventing the need for ex vivo culture, must be investigated.
      To facilitate the development of next-generation, in vivo targeted DC vaccines,
      we characterized the DC interaction and activation potential of the Tobacco
      Mosaic virus (TMV), a plant virus that enjoys a relative ease of production and
      the ability to deliver protein payloads via surface conjugation. In this study we
      show that TMV is readily taken up by mouse bone marrow-derived DCs, in vitro.
      Footpad injection of fluorophore-labeled TMV reveals preferential uptake by
      draining lymph node resident DCs in vivo. Uptake leads to activation, as measured
      by the upregulation of key DC surface markers. When peptide antigen-conjugated
      TMV is injected into the footpad of mice, DC-mediated uptake and activation leads
      to robust antigen-specific CD8(+) T cell responses, as measured by antigen
      specific tetramer analysis. Remarkably, TMV priming induced a greater magnitude T
      cell response than Adenovirus (Ad) priming. Finally, TMV is capable of boosting
      either Ad-induced or TMV-induced antigen-specific T cell responses, demonstrating
      that TMV, uniquely, does not induce neutralizing self-immunity. Overall, this
      study elucidates the in vivo DC delivery and activation properties of TMV and
      indicates its potential as a vaccine vector in stand alone or prime-boost
      strategies. 

PMID- 24923638
TI  - Better vaccines for healthier life. Part II. Conference report of the DCVMN
      International 14th Annual General Meeting Hanoi, Vietnam.
AB  - New vaccines are required to meet the public health challenges of the next
      generation and many unmet global health needs can be addressed by developing
      countries vaccine manufacturers such as lower-cost vaccines based on single-dose,
      thermostable formulations, efficacious in children with compromised
      gastrointestinal tracts. GMP compliance is also a challenge, as sometimes
      innovation and clinical development focus is not accompanied by command of scale
      up and quality assurance for large volume manufacturing and supply. Identifying
      and addressing such challenges, beyond cost and cold-chain space, including
      safety considerations and health worker behavior, regulatory alliances and
      harmonization to foster access to vaccines, will help countries to ensure
      sustainable immunization. There needs to be continuous and close management of
      the global vaccine supply both at national and international levels, requiring
      careful risk management, coordination and cooperation with manufacturers.
      Successful partnership models based on sharing a common goal, mutual respect and
      good communication were discussed among stakeholders. 

PMID- 24923639
TI  - The missing link: family physician perspectives on barriers and enablers to
      prescribing a new Meningococcal B vaccine and other recommended, non-government
      funded vaccines.
AB  - OBJECTIVES: To determine factors influencing Family Physician (FP) uptake of non
      government-funded vaccines, and to explore FP attitudes towards the introduction
      and use of a new vaccine to protect against serogroup B meningococcal disease to
      inform its future introduction into the Australian Immunisation Schedule. DESIGN
      SETTING AND PARTICIPANTS: Quantitative, self-administered state-wide
      questionnaire mailed to all FPs in South Australia (n=1786). Results from 523 FP
      respondents in South Australia, collected between June and October 2013. MAIN
      OUTCOME MEASURES: Self-reported immunisation counselling practices; and
      knowledge, attitudes and barriers to prescribing of Meningococcal B (Men B)
      vaccine and other recommended, non-funded immunisations. RESULTS: The response
      rate was 30% (n=523). While most (59%) respondents had worked in general practice
      for over 20 years, only 39% of all respondents had ever had personal or
      professional experience with a case of invasive meningococcal disease (IMD). Most
      FPs (63%) were aware that a meningococcal B vaccine was being developed, and 93%
      of respondents agreed that this vaccine should be government-funded. FPs ranked
      Men B vaccine as the highest priority to receive funding of eight currently non
      funded immunisation strategies. High vaccine cost and low patient socioeconomic
      status were identified as definite barriers to prescribing non-funded vaccines by
      59% of respondents. Past IMD experience significantly affected attitudes and
      prescribing practices. CONCLUSIONS: IMD, while encountered rarely in clinical
      practice, is considered an important disease to vaccinate against by FPs. Cost
      and perceived low socioeconomic status of patients are substantial barriers to
      FPs prescribing Men B and other non-funded vaccines, and inclusion of such
      vaccines on the National Immunisation Program is likely to improve equity of
      access.

PMID- 24923640
TI  - Economic evaluation of vaccination programme of mumps vaccine to the birth cohort
      in Japan.
AB  - The most common preventative measure against mumps is vaccination with mumps
      vaccine. In most parts of the world, mumps vaccine is routinely delivered through
      live attenuated Measles-Mumps-Rubella (MMR) vaccine. In Japan, receiving mumps
      vaccine is voluntary and vaccine uptake rate is less than 30%. The introduction
      of mumps vaccine into routine vaccination schedule has become one of the current
      topics in health policy and has raised the need to evaluate efficient ways in
      protecting children from mumps-related diseases in Japan. We conducted a cost
      effectiveness analysis with Markov model and calculated incremental cost
      effectiveness ratios (ICERs) of 11 different programmes; a single-dose programme
      at 12-16 months and 10 two-dose programmes with second dose uptakes at ages 2, 3,
      4, 5, 6, 7, 8, 9, 10 and 11. Our base-case analyse set the cost per shot at Y6951
      (US$72; 1US$=96.8). Results show that single-dose programme dominates status quo.
      On the other hand, ICERs of all 10 two-dose programmes are under Y6,300,000
      (US$65,082) per QALY from payer's perspective while it ranged from cost-saving to
      <Y7,000,000 (US$72,314) per QALY from societal perspective. By adopting WHO's
      classification that an intervention is cost-effective if ICER (in QALY) is
      between one and three times of GDP as a criterion, either of the vaccination
      programme is concluded as cost-effective from payer's or societal perspectives.
      Likewise, to uptake second dose at 3-5 years old is more favourable than an
      uptake at any other age because of lower incremental cost-effectiveness ratios. 

PMID- 24923641
TI  - Course of skin symptoms and quality of life in children referred for patch
      testing--a long-term follow-up study.
AB  - Children are patch tested in the same manner as adults, but little has been done
      to establish whether positive or negative findings influence the course of skin
      symptoms. To uncover the course of skin symptoms and the impact of persistent
      eczema on life quality in paediatric patients referred for patch testing, a
      retrospective questionnaire was sent to children and adolescents referred for
      patch testing during a 9-year period. Persistent eczema at follow-up was strongly
      associated to atopic dermatitis, but was not explained by gender, age, contact
      allergy or time span from patch testing to follow-up. Among patients without
      atopic dermatitis, 23.5% reported to suffer from chronic eczema. Persistent
      eczema increased the risk of severe impairment of life quality. Our findings
      indicate a significant risk of childhood eczema becoming chronic and affecting
      life quality considerably. Patch testing did not affect the course of eczema,
      highlighting the difficulties of avoidance behaviour. 

PMID- 24923642
TI  - Contribution to the ethology of Limnotilapia Dardennei (Boulenger, 1899)(Pisces,
      Cichlidae) I. Description of the elementary actions and the patterns of markings.
AB  - This paper deals with the description of the behaviour of Limnotilapia dardennei
      (Boulenger, 1899), a mouthbrooding cichlid of Lake Tanganyika. Each of the
      elementary actions belonging to feeding and comfort behaviour, and aggressive,
      submissive and reproductive behaviour, is described in detail. Since the various
      patterns of markings this cichlid assumes may play an important role in its
      communication system, they are described and their possible significance is
      discussed. It is postulated that they express a territorial status, neutral mood,
      inferiority, surrender, fleeing mood and hiding mood. The mutual relationships of
      the behavioural elements described here and quantitative evidence for the
      postulated significance of the patterns of markings will be treated in subsequent
      papers. We give here a very detailed description of the behaviour of the species,
      because it is a necessity for any further research; for quantitative analysis as
      well as for an experimental approach. 

PMID- 24923643
TI  - Contribution to the ethology of Limnotilapia Dardennei (Boulenger, 1899) (Pisces,
      Cichlidae) II. Social behaviour: Qualitative observations.
AB  - This paper deals with some qualitative observations on the social behaviour of
      Limnotilapia dardennei (Boulenger, 1899), a mouthbrooding cichlid of Lake
      Tanganyika. It makes clear the interrelationships between and the contexts in
      which the elementary actions and patterns of markings - described in a previous
      paper - occur. Quantitative data are not included in this preliminary study. The
      general social and territorial organisation of Limnotilapia dardennei is treated,
      with special reference to fighting behaviour and social hierarchy, as observed in
      combination with territoriality. The reproductive behaviour of this cichlid is of
      the Haplochromis type. We give a short description of courting and spawning, and
      of the brooding habits of the female. This basic knowledge of social behaviour
      was required to allow subsequent quantitative research on the species. 

PMID- 24923644
TI  - The effect of local heating on the calls of the fire-Bellied toad, Bombina
      Bombina (L.).
AB  - In order to determine where the characteristic temperature-dependent changes in
      calling rate, call duration and fundamental frequency of the call of the fire
      bellied toad originate, I heated the head and other parts of the body to various
      temperatures. The greatest increase in calling rate occured when the head was
      heated; it varied with the amount of heating. The changes in calling rate and
      call duration brought about by heating were equally rapid, whereas the frequency
      of the call increased more slowly. This suggests that both calling rate and call
      duration change as a direct result of the effect of heat upon the nervous system.

PMID- 24923645
TI  - Escape versus exploratory activity: An interpretation of rats' behaviour in the
      open field and a light-dark preference test.
AB  - To test the assumption that dark preference in rats can serve as a measure of
      emotionality, dark preference was compared with ambulation and defacation in the
      open field. One group of 80-days-old male rats was handled for seven days;
      another group remained undisturbed. All animals were tested on each of five
      successive days in both a light-dark preference situation and an open field.
      Handled rats ambulated more in the field and stayed less time in the dark than
      non-handled ones. Significant negative correlations were found for the different
      days between open field ambulation and dark preference. Correlations between dark
      preference and open field defacation were positive except on day one. From the
      first to the second trial dark preference increased in both groups while open
      field ambulation decreased. The results were considered to support the hypothesis
      of dark preference as a measure of emotionality. In a second study an
      investigation was made as to whether high initial activity in a new situation is
      brought about by exploration or by an escape tendency. Again one group of male
      albino rats was handled. During testing, half of the handled and half of the non
      handled rats had the chance of escaping from the open field into the adjacent
      home cage. From there the animals had the possibility of re-entering the field.
      The second half of each group had to stay in the field. These latter animals
      showed a remarkable decrease in ambulation from the first to the second trial.
      Rats which had access to their home cages seldom re-entered the field in the
      first trial. In later trials, however, ambulation in the field increased. Non
      handled rats needed more trials before they started investigating the field. It
      was concluded that this result gives more support to an explanation of initial
      activity in terms of escape behaviour. 

PMID- 24923646
TI  - Relations between stimulus-bound eating and intracranial reinforcing strength.
AB  - Rats with monopolar electrodes implanted in the lateral hypothalamus were trained
      to self-stimulate, each under 38 different electrical stimulus values. Stimulus
      bound drinking and eating (SBB) were elicited by stimulating the rats through the
      same electrode with the same parameters and the same rate at which they self
      administered the stimulation. It was observed that the frequency of SBB depended
      on the parameters of the electrical stimulus. The Spearman rank order correlation
      was computed between strength of SBB and the strength of the reinforcing effect
      elicited by brain stimulation. A factor analysis showed that the reinforcing
      process elicited by brain stimulation in this area is composed of several factors
      and that SBB is not loaded in all the factors composing reinforcement. 

PMID- 24923647
TI  - A disjunctive analysis of neonatal approach stimulus prepotence.
AB  - Preliminary results of a disjunctive procedure developed to ascertain the
      relative attractiveness for domestic chicks of auditory and visual stimuli are
      promising. A detailed account of the procedure and initial results is presented.
      Seventy-two Canadian Athens random bred chicks were tested at 24 or 36 h
      posthatch. A repetitive tone (4 per sec, 50 msec duration, 500 Hz) served as the
      auditory stimulus, and a flickering light (3.5 flashes per sec, 0.8 foot candle)
      served as the visual stimulus. An age-dependent change in the attractiveness of
      auditory and visual stimuli obtained with the disjunctive procedure. No change in
      stimulus preference obtained when the stimuli were presented individually. 

PMID- 24923648
TI  - Lipid malnutrition and early development: A study of motor reflexes and
      electrocorticographic activity in the mouse.
AB  - The effects of malnutrition on the ontogeny of reflex and electrocorticographic
      (ECoG) activities were studied in the progeny of mice fed with diets deficient in
      essential fatty acids (EFA-deprived) during the last week of pregnancy. Previous
      findings suggested that prenatal deficiency in essential fatty acids may result
      in extensive modifications of brain lipid biochemistry. The present findings
      indicate that postnatal maturation of malnourished mice occurs at a later age for
      a number of motor reflex activities and for the ECoG patterns. The results also
      indicate that the study of malnutrition through a selective prenatal dietary
      deficiency presents a number of advantages in relation to postnatal
      undernutrition attained by varying the litter size. 

PMID- 24923649
TI  - Food deprivation effects on the running-wheel activity of wild and domestic
      Norway rats.
AB  - Increases in activity typically accompany the food deprivation of Norway rats
      housed in activity wheels. The hypothesis that domestication has reduced the
      intensity of this response to food deprivation was tested by comparing the wheel
      running scores of adult male wild (laboratory-reared) and domestic Norway rats
      when food-deprived and satiated. Wild rats were more active in the wheels than
      domestic subjects, irrespective of the presence or absence of food. However, the
      proportional increase in wheel-running when food deprived was the same for both
      stocks. It is hypothesized that the process of domestication has had little
      influence on the wheel-running response of rats to food deprivation. 

PMID- 24923650
TI  - Gene coexpression patterns during early development of the native Arabidopsis
      reproductive meristem: novel candidate developmental regulators and patterns of
      functional redundancy.
AB  - During very early stages of flower development in Arabidopsis thaliana, a series
      of key decisions are taken. Indeed, the position and the basic patterning of new
      flowers are determined in less than 4 days. Given that the scientific literature
      provides hard evidence for the function of only 10% of A. thaliana genes, we
      hypothesized that although many essential genes have already been identified,
      many poorly characterized genes are likely to be involved in floral patterning.
      In the current study, we use high-throughput sequencing to describe the
      transcriptome of the native inflorescence meristem, the floral meristem and the
      new flower immediately after the start of organ differentiation. We provide
      evidence that our experimental system is reliable and less affected by
      experimental artefacts than a widely used floral induction system. Furthermore,
      we show how these data can be used to identify candidate genes for functional
      studies, and to generate hypotheses of functional redundancies and regulatory
      interactions.

PMID- 24923651
TI  - Synchrony and motor mimicking in chimpanzee observational learning.
AB  - Cumulative tool-based culture underwrote our species' evolutionary success, and
      tool-based nut-cracking is one of the strongest candidates for cultural
      transmission in our closest relatives, chimpanzees. However the social learning
      processes that may explain both the similarities and differences between the
      species remain unclear. A previous study of nut-cracking by initially naive
      chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless
      replicated hammering actions it witnessed. This observation has potentially
      important implications for the nature of the social learning processes and
      underlying motor coding involved. In the present study, model and observer
      actions were quantified frame-by-frame and analysed with stringent statistical
      methods, demonstrating synchrony between the observer's and model's movements,
      cross-correlation of these movements above chance level and a unidirectional
      transmission process from model to observer. These results provide the first
      quantitative evidence for motor mimicking underlain by motor coding in apes, with
      implications for mirror neuron function. 

PMID- 24923652
TI  - Perceived healthcare provider reactions to patient and caregiver use of online
      health communities.
AB  - OBJECTIVE: Many Internet users seek health information through online health
      communities (OHCs) and other social media. Yet few studies assess how individuals
      use peer-generated health information, and many healthcare providers (HCPs)
      believe OHCs interfere with patient-provider relationships. This study explored
      how individuals use OHC content in clinical discussions and how HCPs react to it.
      METHODS: We conducted in-person and virtual focus groups with patients/caregivers
      who visited OHCs (n=89). A trained moderator asked about reasons for membership,
      sharing OHC content with providers, HCP reactions, and preferred roles for HCPs.
      Two researchers independently coded verbatim transcripts (NVivo 9.2) and
      conducted thematic response analysis. RESULTS: Participants described OHCs as
      supplementing information from HCPs, whom they perceived as too busy for detailed
      discussions. Almost all participants shared OHC content with HCPs, although only
      half cited OHCs as the source. Most HCPs reacted negatively to OHC content,
      making participants feel disempowered. Despite these reactions, participants
      continued to use OHCs, and most desired HCP feedback on the accuracy of OHC
      content. CONCLUSIONS: Individuals do not use OHCs to circumvent HCPs but instead
      to gather more in-depth information. PRACTICE IMPLICATIONS: HCPs should discuss
      OHC content with patients to help them avoid misinformation and make more
      informed decisions.

PMID- 24923653
TI  - The predominant pathway of apoptosis in THP-1 macrophage-derived foam cells
      induced by 5-aminolevulinic acid-mediated sonodynamic therapy is the mitochondria
      caspase pathway despite the participation of endoplasmic reticulum stress.
AB  - BACKGROUND: In advanced atherosclerosis, chronic endoplasmic reticulum (ER)
      stress induces foam cells apoptosis and generates inflammatory reactions.
      METHODS: THP-1 macrophage-derived foam cells (FC) were incubated with 1 mM 5
      aminolevulinic acid (ALA). After ALA mediated sonodynamic therapy (ALA-SDT),
      apoptosis of FC was assayed by Annexin V-PI staining. Intracellular reactive
      oxygen species (ROS) and mitochondrial membrane potential were detected by
      staining with CellROX(r) Green Reagent and jc-1. Pretreatment of FC with N
      acetylcysteine (NAC), Z-VAD-FMK or 4-phenylbutyrate (4-PBA), mitochondria
      apoptotic pathway associated proteins and C/EBP-homologous (CHOP) expressions
      were assayed by wertern blotting. RESULTS: Burst of apoptosis of FC was observed
      at 5-hour after ALA-SDT with 6-hour incubation of ALA and 0.4 W/cm(2) ultrasound.
      After ALA-SDT, intracellular ROS level increased and mitochondrial membrane
      potential collapsed. Translocations of cytochrome c from mitochondria into
      cytosol and Bax from cytosol into mitochondria, cleaved caspase 9, cleaved
      caspase 3, upregulation of CHOP, as well as downregulation of Bcl-2 after ALA-SDT
      were detected, which could be suppressed by NAC. Activation of mitochondria
      caspase pathway could not be inhibited by 4-PBA. Cleaved caspase 9 and caspase 3
      as well as apoptosis induced by ALA-SDT could be inhibited by Z-VAD-FMK.
      CONCLUSION: The mitochondria-caspase pathway is predominant in the apoptosis of
      FC induced by ALA-SDT though ER stress participates in.

PMID- 24923654
TI  - Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic
      enzymes and insulin signaling molecules in streptozotocin-cadmium induced
      diabetic nephrotoxic rats.
AB  - Diabetic nephropathy is the kidney disease that occurs as a result of diabetes.
      The present study was aimed to evaluate the therapeutic potential of myricetin by
      assaying the activities of key enzymes of carbohydrate metabolism, insulin
      signaling molecules and renal function markers in streptozotocin (STZ)-cadmium
      (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood
      and tissue samples were collected to determine plasma glucose, insulin,
      hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate
      metabolic enzymes in the liver and insulin signaling molecules in the pancreas
      and skeletal muscle. A significant increase of plasma glucose, glycosylated
      hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary
      albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6
      bisphosphatase and a significant decrease of plasma insulin, hemoglobin,
      hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase
      with insulin signaling molecule expression were found in the STZ-Cd induced
      diabetic nephrotoxic rats. The administration of myricetin significantly
      normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin,
      glycogen phosphorylase and gluconeogenic enzymes and renal function markers with
      increase insulin, glycogen, glycogen synthase and insulin signaling molecule
      expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4),
      insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B
      (PKB). Based on the data, the protective effect of myricetin was confirmed by its
      histological annotation of the pancreas, liver and kidney tissues. These findings
      suggest that myricetin improved carbohydrate metabolism which subsequently
      enhances glucose utilization and renal function in STZ-Cd induced diabetic
      nephrotoxic rats. 

PMID- 24923655
TI  - Developmental programming: prenatal BPA treatment disrupts timing of LH surge and
      ovarian follicular wave dynamics in adult sheep.
AB  - Developmental exposure to BPA adversely affects reproductive function. In sheep,
      prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as
      LH excess and dampened LH surge and perturbs early ovarian gene expression. In
      this study we hypothesized that prenatal BPA treatment will also disrupt ovarian
      follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation
      with 3 different BPA doses (0.05, 0.5, or 5mg/kgBW/day). All female offspring
      were estrus synchronized and transrectal ultrasonography was performed daily for
      22days to monitor ovarian follicular and corpora lutea dynamics. Blood samples
      were collected to assess preovulatory hormonal changes and luteal progesterone
      dynamics. Statistical analysis revealed that the time interval between the
      estradiol rise and the preovulatory LH surge was shortened in the BPA-treated
      females. None of the three BPA doses had an effect on corpora lutea,
      progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory
      follicles. However, differences in follicular count trajectories were evident in
      all three follicular size classes (2-3mm, 4-5mm, and >=6mm) of prenatal BPA
      treated animals compared to controls. Number of follicular waves tended also to
      be more variable in the prenatal BPA-treated groups ranging from 2 to 5
      follicular waves per cycle, while this was restricted to 3 to 4 waves in control
      females. These changes in ovarian follicular dynamics coupled with defects in
      time interval between estradiol rise and preovulatory LH release are likely to
      lead to subfertility in prenatal BPA-treated females. 

PMID- 24923656
TI  - A randomized clinical trial of mesalazine suppository: the usefulness and
      problems of central review of evaluations of colonic mucosal findings.
AB  - BACKGROUND: The methods of evaluating endoscopic mucosal findings and the
      definition of mucosal healing in inflammatory bowel disease have not been
      standardized. AIM: To examine a third-party central review of colonic mucosal
      evaluations. METHODS: A double-blind, placebo-controlled, parallel-group trial
      was performed for 4weeks, which involved continuous administration of a 1-g
      mesalazine suppository to 129 patients with mild to moderate ulcerative colitis
      and active rectal inflammatory findings. Mucosal findings were evaluated by using
      a 4-grade score (0, 1, 2, 3). Reviews by attending physicians were considered the
      primary evaluations. Concurrently, a central review committee of 7
      gastroenterologists served as the third party. RESULTS: The endoscopic remission
      induction rate from the attending physicians' evaluations was 82.8% in the
      mesalazine suppository group and 31.1% in the placebo suppository group, whereas
      the respective rates from the central review committee were 90.6% and 59.0%.
      However, there was a difference of 27.9 percentage points between the remission
      induction rates of the placebo group found by the two groups of raters.
      Differences in the evaluations of mucosal finding scores were also found among
      the third-party reviewers. CONCLUSIONS: The evaluations of the attending
      physicians were consistent with those of the central review committee in showing
      the effectiveness of mesalazine suppository through the index of mucosal healing.
      However, differences were observed among the raters in their evaluations of
      mucosal finding scores. Therefore, standardizing evaluation criteria and
      improving review methods for mucosal findings would enable the more effective use
      of third-party central reviews in clinical drug trials.

PMID- 24923658
TI  - Cell-surface signaling in Pseudomonas: stress responses, iron transport, and
      pathogenicity.
AB  - Membrane-spanning signaling pathways enable bacteria to alter gene expression in
      response to extracytoplasmic stimuli. Many such pathways are cell-surface
      signaling (CSS) systems, which are tripartite molecular devices that allow Gram
      negative bacteria to transduce an extracellular stimulus into a coordinated
      transcriptional response. Typically, CSS systems are composed of the following:
      (1) an outer membrane receptor, which senses the extracellular stimulus; (2) a
      cytoplasmic membrane-spanning protein involved in signal transduction from the
      periplasm to the cytoplasm; and (3) an extracytoplasmic function (ECF) sigma
      factor that initiates expression of the stimulus-responsive gene(s). Members of
      genus Pseudomonas provide a paradigmatic example of how CSS systems contribute to
      the global control of gene expression. Most CSS systems enable self-regulated
      uptake of iron via endogenous (pyoverdine) or exogenous (xenosiderophores, heme,
      and citrate) carriers. Some are also implicated in virulence, biofilm formation,
      and cell-cell interactions. Incorporating insights from the well-characterized
      alginate regulatory circuitry, this review will illustrate common themes and
      variations at the level of structural and functional properties of Pseudomonas
      CSS systems. Control of the expression and activity of ECF sigma factors are
      central to gene regulation via CSS, and the variety of intrinsic and extrinsic
      factors influencing these processes will be discussed.

PMID- 24923659
TI  - Anaerobic digestion of corn stovers for methane production in a novel bionic
      reactor.
AB  - To improve the biogas production from corn stovers, a new bionic reactor was
      designed and constructed. The bionic reactor simulated the rumen digestion of
      ruminants. The liquid was separated from corn stovers and refluxed into corn
      stovers again, which simulated the undigested particles separated from completely
      digested materials and fed back again for further degradation in ruminant
      stomach. Results showed that the bionic reactor was effective for anaerobic
      digestion of corn stovers. The liquid amount and its reflux showed an obvious
      positive correlation with biogas production. The highest biogas production rate
      was 21.6 ml/gVS-addedd, and the total cumulative biogas production was 256.5
      ml/gVS-added. The methane content in biogas ranged from 52.2% to 63.3%. The
      degradation of corn stovers were greatly enhanced through simulating the animal
      digestion mechanisms in this bionic reactor.

PMID- 24923660
TI  - Responses of microbial community and acidogenic intermediates to different water
      regimes in a hybrid solid anaerobic digestion system treating food waste.
AB  - This study investigated the effects of different water regimes in an acidogenic
      leach bed reactor (LBR) during 16-day batch mode food waste digestion. LBRs were
      operated under five water replacement ratios (WRRs) (100%, 75%, 50%, 25% and 5%
      in LBRs R1, R2, R3, R4 and R5, respectively) and methanogenic effluent (ME)
      addition with two leachate recirculation frequencies (once in 24 h and 12 h in
      LBRs R6 and R7, respectively). Results showed that 50-100% WRRs accelerated the
      hydrolysis and acidogenesis with butyrate as the dominant product (~35% of COD);
      whereas 5-25% WRRs promoted propionate production. The ME recirculation enhanced
      protein decomposition and reduced ethanol production. Lactobacillus dominated in
      LBRs with water addition (R1-R5), while Clostridium and hetero-fermenting lactic
      acid bacteria dominated in LBR with ME addition (R7). The highest volatile solid
      degradation (82.9%) and methane yield (0.29 L-CH4/g VS) were obtained with ME
      addition at 0.7 d hydraulic retention time.

PMID- 24923661
TI  - Comments in response to the authors of "human dirofilariasis due to Dirofilaria
      repens in the Russian Federation-remarks concerning epidemiology".

PMID- 24923662
TI  - Purine salvage in the apicomplexan Sarcocystis neurona, and generation of
      hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for
      positive-negative selection of transgenic parasites.
AB  - Sarcocystis neurona is an apicomplexan parasite that causes severe neurological
      disease in horses and marine mammals. The Apicomplexa are all obligate
      intracellular parasites that lack purine biosynthesis pathways and rely on the
      host cell for their purine requirements. Hypoxanthine-xanthine-guanine
      phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that
      function in two complementary purine salvage pathways in apicomplexans.
      Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT,
      AK and all of the major purine salvage enzymes except purine nucleoside
      phosphorylase. Wild-type S. neurona were able to grow in the presence of
      mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting
      that the pathways involving either HXGPRT or AK are functional in this parasite.
      Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a
      positive-negative selection marker. To enable the use of HXGPRT in S. neurona,
      the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was
      transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX,
      and single-cell clones were obtained. These Sn?HXG parasites were susceptible to
      MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In
      summary, S. neurona possesses both purine salvage pathways described in
      apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug
      selection marker in this parasite.

PMID- 24923663
TI  - How nurses and their work environment affect patient experiences of the quality
      of care: a qualitative study.
AB  - BACKGROUND: Healthcare organisations monitor patient experiences in order to
      evaluate and improve the quality of care. Because nurses spend a lot of time with
      patients, they have a major impact on patient experiences. To improve patient
      experiences of the quality of care, nurses need to know what factors within the
      nursing work environment are of influence. The main focus of this research was to
      comprehend the views of Dutch nurses on how their work and their work environment
      contribute to positive patient experiences. METHODS: A descriptive qualitative
      research design was used to collect data. Four focus groups were conducted, one
      each with 6 or 7 registered nurses in mental health care, hospital care, home
      care and nursing home care. A total of 26 nurses were recruited through
      purposeful sampling. The interviews were audiotaped, transcribed and subjected to
      thematic analysis. RESULTS: The nurses mentioned essential elements that they
      believe would improve patient experiences of the quality of nursing care:
      clinically competent nurses, collaborative working relationships, autonomous
      nursing practice, adequate staffing, control over nursing practice, managerial
      support and patient-centred culture. They also mentioned several inhibiting
      factors, such as cost-effectiveness policy and transparency goals for external
      accountability. Nurses feel pressured to increase productivity and report a high
      administrative workload. They stated that these factors will not improve patient
      experiences of the quality of nursing care. CONCLUSIONS: According to
      participants, a diverse range of elements affect patient experiences of the
      quality of nursing care. They believe that incorporating these elements into
      daily nursing practice would result in more positive patient experiences.
      However, nurses work in a healthcare context in which they have to reconcile cost
      efficiency and accountability with their desire to provide nursing care that is
      based on patient needs and preferences, and they experience a conflict between
      these two approaches. Nurses must gain autonomy over their own practice in order
      to improve patient experiences.

PMID- 24923664
TI  - Effects of temperature on the life-history traits of Sancassania (Caloglyphus)
      berlesei (Acari: Astigmatina: Acaridae) feeding on root-knot nematodes,
      Meloidogyne spp. (Nematoda: Meloidogynidae).
AB  - Sancassania (Caloglyphus) berlesei (Michael) is a cosmopolitan and free-living
      mite that inhabits soil as well as laboratory colonies of insects and fungi and
      may have a role as a biocontrol agent of nematodes. In this study, we
      investigated the effects of temperature on the development, reproduction, and
      food consumption of S. berlesei fed egg masses of root-knot nematodes,
      Meloidogyne spp., an important group of agricultural pests. Mites were reared at
      20, 25 or 30  degrees C in the dark. The mites could feed on the nematode egg
      masses, and their developmental time decreased at higher temperatures. Time from
      the egg to adult was similar in females and males reared at the same temperature.
      Adult females lived longer than males at 25  degrees C, but not at 20 or 30 
      degrees C. Generally, females showed a higher rate of food consumption than
      males. Females laid the largest number of eggs at 20 and 25  degrees C (199.7 and
      189.8 eggs/female, respectively), but the intrinsic rate of natural increase was
      highest at 30  degrees C (r m = 0.29). In comparing our data with previous
      reports, we noted that S. berlesei that fed on egg masses of root-knot nematodes
      showed a longer developmental time and a lower reproductive rate than Sancassania
      mites that fed on other diets. Nonetheless, the relatively high value of r m
      (e.g., at 25 and 30  degrees C) suggests that this mite may have certain
      advantages as a biocontrol agent of root-knot nematodes. 

PMID- 24923657
TI  - Neurobiology of microglial action in CNS injuries: receptor-mediated signaling
      mechanisms and functional roles.
AB  - Microglia are the first line of immune defense against central nervous system
      (CNS) injuries and disorders. These highly plastic cells play dualistic roles in
      neuronal injury and recovery and are known for their ability to assume diverse
      phenotypes. A broad range of surface receptors are expressed on microglia and
      mediate microglial 'On' or 'Off' responses to signals from other host cells as
      well as invading microorganisms. The integrated actions of these receptors result
      in tightly regulated biological functions, including cell mobility, phagocytosis,
      the induction of acquired immunity, and trophic factor/inflammatory mediator
      release. Over the last few years, significant advances have been made toward
      deciphering the signaling mechanisms related to these receptors and their
      specific cellular functions. In this review, we describe the current state of
      knowledge of the surface receptors involved in microglial activation, with an
      emphasis on their engagement of distinct functional programs and their roles in
      CNS injuries. It will become evident from this review that microglial homeostasis
      is carefully maintained by multiple counterbalanced strategies, including, but
      not limited to, 'On' and 'Off' receptor signaling. Specific regulation of theses
      microglial receptors may be a promising therapeutic strategy against CNS
      injuries. 

PMID- 24923665
TI  - The bias associated with amplicon sequencing does not affect the quantitative
      assessment of bacterial community dynamics.
AB  - The performance of two sets of primers targeting variable regions of the 16S rRNA
      gene V1-V3 and V4 was compared in their ability to describe changes of bacterial
      diversity and temporal turnover in full-scale activated sludge. Duplicate sets of
      high-throughput amplicon sequencing data of the two 16S rRNA regions shared a
      collection of core taxa that were observed across a series of twelve monthly
      samples, although the relative abundance of each taxon was substantially
      different between regions. A case in point was the changes in the relative
      abundance of filamentous bacteria Thiothrix, which caused a large effect on
      diversity indices, but only in the V1-V3 data set. Yet the relative abundance of
      Thiothrix in the amplicon sequencing data from both regions correlated with the
      estimation of its abundance determined using fluorescence in situ hybridization.
      In nonmetric multidimensional analysis samples were distributed along the first
      ordination axis according to the sequenced region rather than according to sample
      identities. The dynamics of microbial communities indicated that V1-V3 and the V4
      regions of the 16S rRNA gene yielded comparable patterns of: 1) the changes
      occurring within the communities along fixed time intervals, 2) the slow turnover
      of activated sludge communities and 3) the rate of species replacement calculated
      from the taxa-time relationships. The temperature was the only operational
      variable that showed significant correlation with the composition of bacterial
      communities over time for the sets of data obtained with both pairs of primers.
      In conclusion, we show that despite the bias introduced by amplicon sequencing,
      the variable regions V1-V3 and V4 can be confidently used for the quantitative
      assessment of bacterial community dynamics, and provide a proper qualitative
      account of general taxa in the community, especially when the data are obtained
      over a convenient time window rather than at a single time point. 

PMID- 24923666
TI  - Identification, classification, and growth of moa chicks (Aves: Dinornithiformes)
      from the genus Euryapteryx.
AB  - BACKGROUND: The analysis of growth in extinct organisms is difficult. The general
      lack of skeletal material from a range of developmental states precludes
      determination of growth characteristics. For New Zealand's extinct moa we have
      available to us a selection of rare femora at different developmental stages that
      have allowed a preliminary determination of the early growth of this giant
      flightless bird. We use a combination of femora morphometrics, ancient DNA, and
      isotope analysis to provide information on the identification, classification,
      and growth of extinct moa from the genus Euryapteryx. RESULTS: Using ancient DNA,
      we identify a number of moa chick bones for the species Euryapteryx curtus,
      Dinornis novaezealandiae, and Anomalopteryx didiformis, and the first chick bone
      for Pachyornis geranoides. Isotope analysis shows that ?15N levels vary between
      the two known size classes of Euryapteryx, with the larger size class having
      reduced levels of ?15N. A growth series for femora of the two size classes of
      Euryapteryx shows that early femora growth characteristics for both classes are
      almost identical. Morphometric, isotopic, and radiographic analysis of the
      smallest Euryapteryx bones suggests that one of these femora is from a freshly
      hatched moa at a very early stage of development. CONCLUSION: Using morphometric,
      isotopic, and ancient DNA analyses have allowed the determination of a number of
      characteristics of rare moa chick femora. For Euryapteryx the analyses suggest
      that the smaller sized class II Euryapteryx is identical in size and growth to
      the extant Darwin's rhea.

PMID- 24923668
TI  - Synthetic gestagens exert differential effects on arterial thrombosis and aortic
      gene expression in ovariectomized apolipoprotein E-deficient mice.
AB  - BACKGROUND AND PURPOSE: Combined hormone replacement therapy with oestrogens plus
      the synthetic progestin medroxyprogesterone acetate (MPA) is associated with an
      increased risk of thrombosis. However, the mechanisms of this pro-thrombotic
      effect are largely unknown. The purpose of this study was to: (i) compare the pro
      thrombotic effect of MPA with another synthetic progestin, norethisterone acetate
      (NET-A), (ii) determine if MPA's pro-thrombotic effect can be antagonized by the
      progesterone and glucocorticoid receptor antagonist mifepristone and (iii)
      elucidate underlying mechanisms by comparing aortic gene expression after chronic
      MPA with that after NET-A treatment. EXPERIMENTAL APPROACH: Female apolipoprotein
      E-deficient mice were ovariectomized and treated with placebo, MPA, a combination
      of MPA + mifepristone or NET-A for 90 days on a Western-type diet. Arterial
      thrombosis was measured in vivo in a photothrombosis model. Aortic gene
      expression was analysed using microarrays; GeneOntology and KEGG pathway analyses
      were conducted. KEY RESULTS: MPA's pro-thrombotic effects were prevented by
      mifepristone, while NET-A did not affect arterial thrombosis. Aortic gene
      expression analysis showed, for the first time, that gestagens induce similar
      effects on a set of genes potentially promoting thrombosis. However, in NET-A
      treated mice other genes with potentially anti-thrombotic effects were also
      affected, which might counterbalance the effects of the pro-thrombotic genes.
      CONCLUSIONS AND IMPLICATIONS: The pro-thrombotic effects of synthetic progestins
      appear to be compound-specific, rather than representing a class effect of
      gestagens. Furthermore, the different thrombotic responses elicited by MPA and
      NET-A might be attributed to a more balanced, 'homeostatic' gene expression
      induced in NET-A- as compared with MPA-treated mice.

PMID- 24923669
TI  - Is single-stage revision according to a strict protocol effective in treatment of
      chronic knee arthroplasty infections?
AB  - BACKGROUND: The increasing number of patients experiencing periprosthetic total
      knee arthroplasty (TKA) infections and the cost of treating them suggest that we
      seek alternatives to two-stage revision. Single-stage revision is a potential
      alternative to the standard two-stage procedure because it involves only one
      surgical procedure, so if it is comparably effective, it would be associated with
      less patient morbidity and lower cost. QUESTIONS/PURPOSES: We compared (1) the
      degree to which our protocol of a highly selective single-stage revision approach
      achieved infection control compared with a two-stage revision approach to TKA
      infections; and (2) Knee Society scores and radiographic evidence of implant
      fixation between the single-stage and two-stage patients who were treated for
      more complicated infections. METHODS: Between 2004 and 2009, we treated 102
      patients for chronic TKA infections, of whom 28 (27%) were treated using a single
      stage approach and 74 (73%) were treated using a two-stage approach. All patients
      were available for followup at a minimum of 3 years (mean, 6.5 years; range, 3-9
      years). The indications for using a single-stage approach were minimal/moderate
      bone loss, the absence of immunocompromise, healthy soft tissues, and a known
      organism with known sensitivities for which appropriate antibiotics are
      available. Participants included 38 men and 64 women with a mean age of 65 years
      (range, 45-87 years). We used the Musculoskeletal Infection Society definition of
      periprosthetic joint infection to confirm infection control at the last followup
      appointment. Radiographs were evaluated for signs of loosening, and patients
      completed Knee Society Scores for clinical evaluation. RESULTS: None of the
      patients in the single-stage revision group developed recurrence of infection,
      and five patients (93%) in the two-stage revision group developed reinfection
      (p=0.16). Patients treated with a single-stage approach had higher Knee Society
      scores than did patients treated with the two-stage approach (88 versus 76,
      p<0.001). However, radiographic findings showed a well-fixed prosthesis in all
      patients with no evidence of loosening at last followup in either group.
      CONCLUSIONS: Our data provide preliminary support to the use of a single-stage
      approach in highly selected patients with chronically infected TKAs as an
      alternative to a two-stage procedure. However, larger, multicenter, prospective
      trials are called for to validate our findings. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24923670
TI  - Preoperative fine needle aspiration of axillary lymph nodes in breast cancer:
      clinical utility, diagnostic accuracy and potential pitfalls.
AB  - OBJECTIVE: This study evaluates the diagnostic accuracy of axillary lymph node
      fine needle aspiration (FNA) cytology in breast cancer and correlates it with
      clinical parameters/outcomes. STUDY DESIGN: A total of 91 females underwent FNA
      of axillary lymph nodes at our institution from January 2007 to February 2013.
      The cases were classified as 'positive', 'negative for malignancy' and
      'nondiagnostic'. RESULTS: Forty-six cases (50.5%) had a histologic follow-up (4.4
      +/- 3.1 months); of these, 22 (47.8%) were true positive, 7 (15.2%) were true
      negative, 2 (4.3%) were false negative, 5 (11%) were false positive and 10
      (21.7%) were nondiagnostic. However, cytological review of all false positive and
      false negative cases confirmed the presence or absence of tumor, respectively.
      All false positive cases had undergone preoperative neoadjuvant chemotherapy,
      with no residual tumor present, and a treatment effect identified only
      histologically. Meanwhile, the 2 false negative cases involved micrometastasis
      (<= 1.5 mm). Thus, if we exclude these false positive cases (complete
      responders), then the sensitivity, specificity, positive predictive value and
      negative predictive value were 91.7, 100, 100 and 77.8%, respectively. All
      preoperative FNA-positive axillary lymph nodes were spared from sentinel lymph
      node biopsy except for 3 of 27 (11.1%). CONCLUSION: We suggest that axillary
      lymph node FNA is a highly sensitive technique with a low false negative rate
      (4.3%) and a diagnostic accuracy of 93.5%.

PMID- 24923672
TI  - Balloon-occluded retrograde transvenous obliteration for recurrent fundal gastric
      variceal bleeding in an adolescent.
AB  - Gastric variceal bleeding is associated with high morbidity and mortality.
      Balloon-occluded retrograde transvenous obliteration is a relatively new
      treatment used to control bleeding gastric varices that involves transvenous
      sclerosis of gastric varices through a spontaneous gastrorenal shunt. Here, we
      report on a 14-yr-old patient that underwent balloon-occluded retrograde
      transvenous obliteration for refractory bleeding fundal varices in the setting of
      esophageal varices and cirrhosis, which did not respond to medical management or
      endoscopic injection. This case report serves as a reminder that balloon-occluded
      retrograde transvenous obliteration can successfully control fundal variceal
      bleeding in pediatric patients and may serve as a bridge to liver
      transplantation. 

PMID- 24923671
TI  - Circulating levels of tumor necrosis factor-alpha receptor 2 are increased in
      heart failure with preserved ejection fraction relative to heart failure with
      reduced ejection fraction: evidence for a divergence in pathophysiology.
AB  - BACKGROUND: Various pathways have been implicated in the pathogenesis of heart
      failure (HF) with preserved ejection fraction (HFPEF). Inflammation in response
      to comorbid conditions, such as hypertension and diabetes, may play a
      proportionally larger role in HFPEF as compared to HF with reduced ejection
      fraction (HFREF). METHODS AND RESULTS: This study investigated inflammation
      mediated by the tumor necrosis factor-alpha (TNFalpha) axis in community-based
      cohorts of HFPEF patients (n = 100), HFREF patients (n = 100) and healthy
      controls (n = 50). Enzyme-linked immunosorbent assays were used to investigate
      levels of TNFalpha, its two receptors (TNFR1 and TNFR2), and a non-TNFalpha
      cytokine, interleukin-6 (IL-6), in plasma derived from peripheral blood samples.
      Plasma levels of TNFalpha and TNFR1 were significantly elevated in HFPEF relative
      to controls, while levels of TNFR2 were significantly higher in HFPEF than both
      controls and HFREF. TNFalpha, TNFR1 and TNFR2 were each significantly associated
      with at least two of the following: age, estimated glomerular filtration rate,
      hypertension, diabetes, smoking, peripheral vascular disease or history of atrial
      fibrillation. TNFR2 levels were also significantly associated with increasing
      grade of diastolic dysfunction and severity of symptoms in HFPEF. CONCLUSIONS:
      Inflammation mediated through TNFalpha and its receptors, TNFR1 and TNFR2, may
      represent an important component of a comorbidity-induced inflammatory response
      that partially drives the pathophysiology of HFPEF.

PMID- 24923673
TI  - Epidemiology and outcome of nosocomial candidemia in elderly patients admitted
      prevalently in medical wards.
AB  - BACKGROUND AND AIMS: Candidemia represents an important cause of morbidity and
      mortality. To-date, the highest rates of candidemia occur in elderly patients,
      but there are few data on such patient population. The aims of this study were to
      evaluate the epidemiology, treatment and outcome of candidemia in an elderly
      patient population. METHODS: Nosocomial candidemia episodes occurring in a
      university general hospital were included in this study. Demographic, clinical,
      and Candida susceptibility testing data were retrospectively collected. Potential
      risk factors for 30-day crude mortality rate including host factors, Candida
      species, concomitant bacteremia, severity of sepsis, and management of fungemia
      were assessed by hazard risk (HR) analyses. RESULTS: 145 consecutive episodes of
      candidemia occurring in 140 patients with a median age of 81 years (interquartile
      range, 78-86 years) were analyzed. At the onset of candidemia, 98 (67.6 %) cases
      were hospitalized in medical wards. Candida albicans accounted for 55 % of all
      candidemia episodes. Overall, resistance to fluconazole was detected in 8.0 % of
      Candida isolates. Crude hospital mortality at 30 days was 46 %. Failure to
      receive adequate antifungal therapy was the significant risk factor for death on
      multivariable analysis (adjusted HR 1.87, 95 % CI 0.94-2.79). DISCUSSION AND
      CONCLUSIONS: Over two-thirds of elderly patients with candidemia are admitted to
      medical wards in our series. 30-day crude mortality is high and seems to be
      related to inadequate antifungal therapy. Increased awareness of the burden of
      this disease also in medical wards is strongly required to recognize and treat
      properly this severe infection.

PMID- 24923674
TI  - Patterns of sequencing coverage bias revealed by ultra-deep sequencing of
      vertebrate mitochondria.
AB  - BACKGROUND: Genome and transcriptome sequencing applications that rely on
      variation in sequence depth can be negatively affected if there are systematic
      biases in coverage. We have investigated patterns of local variation in
      sequencing coverage by utilising ultra-deep sequencing (>100,000X) of mtDNA
      obtained during sequencing of two vertebrate genomes, wolverine (Gulo gulo) and
      collared flycatcher (Ficedula albicollis). With such extreme depth, stochastic
      variation in coverage should be negligible, which allows us to provide a very
      detailed, fine-scale picture of sequence dependent coverage variation and
      sequencing error rates. RESULTS: Sequencing coverage showed up to six-fold
      variation across the complete mtDNA and this variation was highly repeatable in
      sequencing of multiple individuals of the same species. Moreover, coverage in
      orthologous regions was correlated between the two species and was negatively
      correlated with GC content. We also found a negative correlation between the site
      specific sequencing error rate and coverage, with certain sequence motifs
      "CCNGCC" being particularly prone to high rates of error and low coverage.
      CONCLUSIONS: Our results demonstrate that inherent sequence characteristics
      govern variation in coverage and suggest that some of this variation, like GC
      content, should be controlled for in, for example, RNA-Seq and detection of copy
      number variation.

PMID- 24923675
TI  - Quantitative neutron imaging of water distribution, venation network and sap flow
      in leaves.
AB  - MAIN CONCLUSION: Quantitative neutron imaging is a promising technique to
      investigate leaf water flow and transpiration in real time and has perspectives
      towards studies of plant response to environmental conditions and plant water
      stress. The leaf hydraulic architecture is a key determinant of plant sap
      transport and plant-atmosphere exchange processes. Non-destructive imaging with
      neutrons shows large potential for unveiling the complex internal features of the
      venation network and the transport therein. However, it was only used for two
      dimensional imaging without addressing flow dynamics and was still unsuccessful
      in accurate quantification of the amount of water. Quantitative neutron imaging
      was used to investigate, for the first time, the water distribution in veins and
      lamina, the three-dimensional venation architecture and sap flow dynamics in
      leaves. The latter was visualised using D2O as a contrast liquid. A high dynamic
      resolution was obtained by using cold neutrons and imaging relied on radiography
      (2D) as well as tomography (3D). The principle of the technique was shown for
      detached leaves, but can be applied to in vivo leaves as well. The venation
      network architecture and the water distribution in the veins and lamina unveiled
      clear differences between plant species. The leaf water content could be
      successfully quantified, though still included the contribution of the leaf dry
      matter. The flow measurements exposed the hierarchical structure of the water
      transport pathways, and an accurate quantification of the absolute amount of
      water uptake in the leaf was possible. Particular advantages of neutron imaging,
      as compared to X-ray imaging, were identified. Quantitative neutron imaging is a
      promising technique to investigate leaf water flow and transpiration in real time
      and has perspectives towards studies of plant response to environmental
      conditions and plant water stress.

PMID- 24923676
TI  - Characterization of an apple TT2-type R2R3 MYB transcription factor functionally
      similar to the poplar proanthocyanidin regulator PtMYB134.
AB  - MAIN CONCLUSION: The apple MdMYB9 gene encodes a positive regulator of
      proanthocyanidin synthesis that activates anthocyanidin reductase promoters from
      apple and poplar via interaction with basic helix-loop-helix proteins. The
      regulation of proanthocyanidins (PAs, condensed tannins) is of great importance
      in food plants due to the many benefits of PAs in the human diet. Two candidate
      flavonoid MYB regulators, MdMYB9 and MdMYB11, were cloned from apple (Malus *
      domestica) based on their similarity to known MYB PA regulators. Transcript
      accumulation of both MdMYB9 and MdMYB11 was induced by high light and wounding,
      similar to the poplar (Populus spp) PA regulator PtMYB134. In transient
      activation assays with various basic helix-loop-helix (bHLH) co-regulators,
      MdMYB9 activated apple and poplar anthocyanidin reductase (ANR) promoters, while
      MdMYB11 showed no activity. Potential transcription factor binding elements were
      found within several ANR promoters, and the importance of the bHLH binding site
      (E-box) on ANR promoter activation was demonstrated via mutational analysis. The
      ability of MdMYB9 and PtMYB134 to reciprocally activate ANR promoters from both
      apple and poplar and to partner with heterologous bHLH co-factors from these
      plants confirms the high degree of conservation of PA regulatory complexes across
      species. The similarity in apple and poplar PA regulation suggests that
      regulatory genes from poplar could be effectively employed for metabolic
      engineering of the PA pathway in apple.

PMID- 24923678
TI  - MoS2/graphene cocatalyst for efficient photocatalytic H2 evolution under visible
      light irradiation.
AB  - Exploiting noble-metal-free cocatalysts is of huge interest for photocatalytic
      water splitting using solar energy. Here we report a composite material
      consisting of CdS nanocrystals grown on the suface of a nanosized MoS2/graphene
      hybrid as a high-performance noble-metal-free photocatalyst for H2 evolution
      under visible light irradiation. Through the optimizing of each component
      proportion, the MoS2/G-CdS composite showed the highest photocatalytic H2
      production activity when the content of the MoS2/graphene cocatalyst is 2.0 wt %
      and the molar ratio of MoS2 to graphene is 1:2. The photocatalytic H2 evolution
      activity of the proposed MoS2/G-CdS composite was tested and compared in Na2S
      Na2SO3 solution and lactic acid solution. A 1.8 mmol/h H2 evolution rate in
      lactic acid solution corresponding to an AQE of 28.1% at 420 nm is not only
      higher than the case in Na2S-Na2SO3 solution of 1.2 mmol/h but also much higher
      than that of Pt/CdS in lactic acid solution. The relative mechanism has been
      investigated. It is believed that this kind of MoS2/G-CdS composite would have
      great potential as a promising photocatalyst with high efficiency and low cost
      for photocatalytic H2 evolution reaction. 

PMID- 24923677
TI  - Raphanusanin-mediated resistance to pathogens is light dependent in radish and
      Arabidopsis thaliana.
AB  - Raphanusanin (Ra) is a light-induced inhibitor of hypocotyl growth that responds
      to unilateral blue light illumination in radish seedlings. We have previously
      shown that Ra regulates genes that are involved in common defense mechanisms.
      Many genes that are induced by Ra are also positively regulated by early blue
      light. To extend the understanding of the role of Ra in pathogen defense, we
      evaluated the effects of Ra on radish and Arabidopsis thaliana (A. thaliana)
      infected with the necrotrophic pathogen Botrytis cinerea (B. cinerea) and
      biotrophic pathogen Pseudomonas syringae (P. syringae). Radish and A. thaliana
      were found to be resistant to both pathogens when treated with Ra, depending on
      the concentration used. Interestingly, Ra-mediated resistance to P. syringae is
      dependent on light because Ra-treated seedlings exhibited enhanced susceptibility
      to P. syringae infection when grown in the dark. In addition to regulating the
      biotic defense response, Ra inhibited seed germination and root elongation and
      enhanced the growth of root hairs in the presence of light in radish and A.
      thaliana. Our data suggest that Ra regulates the expression of a set of genes
      involved in defense signaling pathways and plays a role in pathogen defense and
      plant development. Our results show that light may be generally required not only
      for the accumulation of Ra but also for its activation during the pathogen
      defense response. 

PMID- 24923679
TI  - Evaluation of factors predicting recoverability of renal function after
      pyeloplasty in adults.
AB  - AIM: To analyze the status of renal function after pyeloplasty in a large
      contemporary adult series and to detect which variables predict improvement of
      renal function. MATERIALS AND METHODS: 85 adult patients were retrospectively
      identified who had undergone pyeloplasty between January 2002 and May 2011 with
      available pre- and postoperative diuretic scintigraphy. Preoperative differential
      renal function (DRF) and single-kidney GFR (SKGFR) were obtained by (99m)Tc-MAG-3
      diuretic scintigraphy. Baseline-weighted (bw-) DRF and SKGFR were calculated
      between baseline conditions and time of last follow-up. Factors that explain the
      variance of bw-DRF and bw-SKGFR were determined. RESULTS: The mean (SD)
      preoperative DRF significantly increased from 34% (11.6) to 37.2% (11.8) after
      pyeloplasty (p < 0.001). Similarly, mean (SD) SKGFR showed a significant
      improvement from 31.2 (12.9) to 35.9 (15) ml/min (p < 0.001). Patients with a
      lower baseline DRF (<=40%) showed a significant improvement as opposed to those
      with a higher baseline DRF (>40%) (p < 0.001 and 0.3, respectively). Baseline DRF
      and cortical thickness explained the variance in bw-DRF and bw-SKGFR with more
      contribution of baseline DRF. CONCLUSIONS: Renal function showed improvement
      after pyeloplasty in adults and preoperative DRF and cortical thickness were the
      predicting variables.

PMID- 24923680
TI  - Involvement of YODA and mitogen activated protein kinase 6 in Arabidopsis post
      embryogenic root development through auxin up-regulation and cell division plane
      orientation.
AB  - The role of YODA MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 4 (MAPKKK4)
      upstream of MITOGEN ACTIVATED PROTEIN KINASE 6 (MPK6) was studied during post
      embryonic root development of Arabidopsis thaliana. Loss- and gain-of-function
      mutants of YODA (yda1 and DeltaNyda1) were characterized in terms of root
      patterning, endogenous auxin content and global proteomes. We surveyed
      morphological and cellular phenotypes of yda1 and DeltaNyda1 mutants suggesting
      possible involvement of auxin. Endogenous indole-3-acetic acid (IAA) levels were
      up-regulated in both mutants. Proteomic analysis revealed up-regulation of auxin
      biosynthetic enzymes tryptophan synthase and nitrilases in these mutants. The
      expression, abundance and phosphorylation of MPK3, MPK6 and MICROTUBULE
      ASSOCIATED PROTEIN 65-1 (MAP65-1) were characterized by quantitative polymerase
      chain reaction (PCR) and western blot analyses and interactions between MAP65-1,
      microtubules and MPK6 were resolved by quantitative co-localization studies and
      co-immunoprecipitations. yda1 and DeltaNyda1 mutants showed disoriented cell
      divisions in primary and lateral roots, abortive cytokinesis, and differential
      subcellular localization of MPK6 and MAP65-1. They also showed deregulated
      expression of TANGLED1 (TAN1), PHRAGMOPLAST ORIENTING KINESIN 1 (POK1), and GAMMA
      TUBULIN COMPLEX PROTEIN 4 (GCP4). The findings that MPK6 localized to preprophase
      bands (PPBs) and phragmoplasts while the mpk6-4 mutant transformed with MPK6AEF
      (alanine (A)-glutamic acid (E)-phenylanine (F)) showed a root phenotype similar
      to that of yda1 demonstrated that MPK6 is an important player downstream of YODA.
      These data indicate that YODA and MPK6 are involved in post-embryonic root
      development through an auxin-dependent mechanism regulating cell division and
      mitotic microtubule (PPB and phragmoplast) organization. 

PMID- 24923681
TI  - Coordinated DNA dynamics during the human telomerase catalytic cycle.
AB  - The human telomerase reverse transcriptase (hTERT) utilizes a template within the
      integral RNA subunit (hTR) to direct extension of telomeres. Telomerase exhibits
      repeat addition processivity (RAP) and must therefore translocate the nascent DNA
      product into a new RNA:DNA hybrid register to prime each round of telomere repeat
      synthesis. Here, we use single-molecule FRET and nuclease protection assays to
      monitor telomere DNA structure and dynamics during the telomerase catalytic
      cycle. DNA translocation during RAP proceeds through a previously uncharacterized
      kinetic substep during which the 3'-end of the DNA substrate base pairs
      downstream within the hTR template. The rate constant for DNA primer realignment
      reveals this step is not rate limiting for RAP, suggesting a second slow
      conformational change repositions the RNA:DNA hybrid into the telomerase active
      site and drives the extrusion of the 5'-end of the DNA primer out of the enzyme
      complex. 

PMID- 24923683
TI  - Colloids for fluid resuscitation: what is their role in patients with shock?
AB  - BACKGROUND: Fluid therapy is widely used in critically ill patients to restore
      effective intravascular volume and improve organ perfusion. Recent studies have
      questioned the administration of colloid-based solutions, especially if
      containing hydroxyethyl starch (HES), in different ICU populations; however,
      there is still uncertainty on the use of colloids as initial fluid therapy for
      early resuscitation. METHODS: The aim of this study was to investigate the effect
      of two different resuscitation fluid strategies on the mortality of patients with
      shock. In a multicentric (57 ICUs), controlled, open-label trial (from February
      2003 to August 2012), the authors randomized patients with signs of acute
      hypovolemia, defined by the combination of hypotension, evidence of low filling
      pressures or cardiac index and at least two signs of tissue hypoperfusion (such
      as altered consciousness, mottled skin, oliguria, lactate levels > 2 mmol/L), to
      received either a colloid- or crystalloid-based therapy. Both cohorts received
      maintenance fluids consisting in isotonic crystalloids and albumin in case of
      severe hypoalbuminemia (<2 g/dL). Exclusion criteria included previous fluid
      therapy, pregnancy, brain death, extended burns, chronic hemodialysis or liver
      disease, known coagulopathy, acute anaphylaxis, dehydration and hypotension due
      to sedative drugs. RESULTS: Among the 6498 eligible patients, 2857 were
      eventually randomized in one of the two groups. The 28-day mortality was 25.4% in
      the colloid and 27.0% in the crystalloid group (P=0.26). In the sub-group
      analysis, similar mortality rates were reported for shock due to hypovolemia,
      sepsis or trauma. Also, the use of continuous renal replacement therapy was
      similar between groups (11.0% vs. 12.5%, P=0.19). There were more days alive
      without mechanical ventilation or vasopressors during the first 7 and 28 days and
      a lower 90-day mortality in the colloid group. CONCLUSION: These data suggest
      that mortality was not increased and probably decreased with the use of colloids
      in different forms of shock requiring early fluid resuscitation. We discussed
      herein some methodological issues that may explain the discrepancies of this
      trial with the other studies developed in the same field.

PMID- 24923684
TI  - Retraction note to: Cryptomycota: the missing link. Protein Cell 2012, 3(3): 161
      2.

PMID- 24923682
TI  - Measuring and predicting long-term outcomes in older survivors of critical
      illness.
AB  - Older adults (age >=65 years) now initially survive what were previously fatal
      critical illnesses, but long-term mortality and disability after critical illness
      remain high. Most studies show that the majority of deaths among older ICU
      survivors occur during the first 6 to 12 months after hospital discharge. Less is
      known about the relationship between critical illness and subsequent cause of
      death, but longitudinal studies of ICU survivors of pneumonia, stroke, and those
      who require prolonged mechanical ventilation suggest that many debilitated older
      ICU survivors die from recurrent infections and sepsis. Recent studies of older
      ICU survivors have created a new standard for longitudinal critical care outcomes
      studies with a systematic evaluation of pre-critical illness comorbidities and
      disability and detailed assessments of physical and cognitive function after
      hospital discharge. These studies show that after controlling for pre-morbid
      health, older ICU survivors experience large and persistent declines in cognitive
      and physical function after critical illness. Long-term health-related quality-of
      life studies suggest that some older ICU survivors may accommodate to a degree of
      physical disability and still report good emotional and social well-being, but
      these studies are subject to survivorship and proxy-response bias. In order to
      risk-stratify older ICU survivors for long-term (6-12 months) outcomes, we will
      need a paradigm shift in the timing and type of predictors measured. Emerging
      literature suggests that the initial acuity of critical illness will be less
      important, whereas prehospitalization estimates of disability and frailty, and,
      in particular, measures of comorbidity, frailty, and disability near the time of
      hospital discharge will be essential in creating reliable long-term risk
      prediction models. 

PMID- 24923685
TI  - Multinational, multicentre, randomised, open-label study evaluating the impact of
      a 91-day extended regimen combined oral contraceptive, compared with two 28-day
      traditional combined oral contraceptives, on haemostatic parameters in healthy
      women.
AB  - OBJECTIVES: To evaluate the impact of a 91-day extended regimen combined oral
      contraceptive (150 MUg levonorgestrel [LNG]/30 MUg ethinylestradiol [EE] for 84
      days, followed by 10 MUg EE for seven days [Treatment 1]) compared with two
      traditional 21/7 regimens (21 days 150 MUg LNG/30 MUg EE [Treatment 2] or 150 MUg
      desogestrel [DSG]/30 MUg EE [Treatment 3], both with seven days' hormone free),
      on several coagulation factors and thrombin formation markers. METHODS:
      Randomised, open-label, parallel-group comparative study involving healthy women
      (18-40 years). The primary endpoint was change from baseline in prothrombin
      fragment 1 + 2 (F1 + 2) levels over six months. RESULTS: A total of 187 subjects
      were included in the primary analysis. In all groups, mean F1 + 2 values were
      elevated after six months of treatment. Changes were comparable between
      Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L,
      respectively) but noticeably larger after Treatment 3 (least squares mean change:
      592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of
      Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95%
      confidence interval [- 18.3 pmol/L] > - 130 pmol/L). CONCLUSIONS: The LNG/EE
      regimens had similar effects on F1 + 2. Noninferiority was demonstrated between
      extended regimen LNG/EE and DSG/EE.

PMID- 24923686
TI  - Moderate value of non-contrast magnetic resonance imaging after non-dislocating
      shoulder trauma.
AB  - PURPOSE: The purpose of the present study was to determine the value of shoulder
      magnetic resonance imaging (MRI) obtained in the community setting interpreted by
      musculoskeletal radiologists in patients with shoulder pain initiated by a single
      non-dislocating shoulder trauma. METHODS: In 56 of 61 consecutive patients who
      underwent shoulder arthroscopy due to pain after a single non-dislocating
      shoulder trauma, the data sets of non-contrast MRI were complete. These were
      retrospectively interpreted by three radiologists specialized on musculoskeletal
      MRI who were blinded for patients' history and who did not have access to the
      reports of arthroscopy. Standard evaluation forms were used to assess the MRIs
      for superior labrum anterior and posterior (SLAP) lesions, anterior or posterior
      labrum lesions, lesions of the long head of biceps tendon (LHB) and for partial
      tears of the supraspinatus tendon and the upper quarter of the subscapularis
      tendon. Quality of the MRI was assessed by each radiologist on a four-point
      scale. RESULTS: The pooled sensitivity for the three radiologists for the
      detection of SLAP lesions was 45.0 %, for anterior or posterior labrum tears 77.8
      and 66.7 %, for lesions of the LHB 63.2 % and for partial tears of the
      supraspinatus or subscapularis tendon tears 84.8 and 33.3 %. Corresponding inter
      rater reliabilities were poor (SLAP lesions) to substantial (anterior labrum
      tears). Quality of MRI only influenced the accuracy for the detection of
      posterior labrum tears. CONCLUSION: A non-contrast shoulder MRI obtained in the
      community setting after non-dislocating shoulder trauma has a moderate
      sensitivity for most intraarticular pathologies when interpreted by
      musculoskeletal radiologists. Accuracy is dependent on the observer and not on
      the assessed quality. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 24923687
TI  - Locked bucket-handle type bony Bankart lesion resulting from manipulation.
AB  - A patient who underwent manipulation for stiffness accompanying a rotator cuff
      tear experienced a complication consisting of a bony Bankart lesion connected to
      the superior and inferior labrum. This lesion was displaced posteriorly, locked
      behind the humeral head and blocking the reduction. Attachment of the labrum to
      this fragment made reduction and fixation easier. This bony Bankart lesion was
      fixed successfully by arthroscopic placement of knotless suture anchors. Level of
      evidence Case report, Level IV. 

PMID- 24923688
TI  - Outcome of distal clavicle resection in patients with acromioclavicular joint
      osteoarthritis and full-thickness rotator cuff tear.
AB  - PURPOSE: The purpose of this study was to examine the impact of distal clavicle
      resection (DCR) on subjective and objective outcome measures in patients with
      acromioclavicular (AC) joint osteoarthritis (OA) and rotator cuff tear. METHODS:
      Prospectively collected data of consecutive patients with arthroscopic evidence
      of OA of the ACJ with complete data at 2 years were used for the data analysis.
      Patients with moderate-to-severe OA of the AC joint underwent a DCR in
      conjunction with rotator cuff repair, while patients with mild OA of the ACJ
      underwent surgery related to concomitant rotator cuff tear without a DCR.
      RESULTS: Data of 184 (72 females, 112 males, mean age: 62) patients with rotator
      cuff tear and varying degrees of OA of the AC joint were used for the analysis.
      Of 184 patients, 144 (78 %) had a resection of distal clavicle (resection group)
      and 40 (22 %) did not have a resection (no-resection group). Both groups showed a
      statistically significant (p < 0.0001) improvement in the American Shoulder and
      Elbow Surgeons (ASES) scores, Constant Murley score, and strength. Multivariable
      analysis showed that lower pre-operative ASES scores (higher disability), having
      a larger tear, an active compensation claim, and not having a DCR, had a negative
      impact on post-operative ASES scores. CONCLUSION: When untreated surgically, even
      mild arthroscopic findings of AC joint OA may lead to a poorer outcome after
      rotator cuff repair. Further characterisation of patients in whom mild
      arthroscopic findings of OA of AC joint are clinically significant and warrant
      resection is needed. LEVEL OF EVIDENCE: Retrospective outcome study, Level II.

PMID- 24923689
TI  - Does knee stability in the coronal plane in extension affect function and outcome
      after total knee arthroplasty?
AB  - PURPOSE: The aim of the present study was to clarify whether varus-valgus
      laxities under static stress in extension, femoral condylar lift-off during
      walking, and patient-reported outcomes after total knee arthroplasty (TKA) were
      correlated with each other. METHODS: Ninety-four knees, which had undergone
      posterior-stabilized TKA, were analysed. The varus-valgus laxity during knee
      extension was measured using a stress radiograph. New Knee Society Score (KSS)
      questionnaires were mailed to all patients. Correlations between the values of
      stress radiographs and KSS were analysed. Additionally, continuous radiological
      images were taken of 15 patients while each walked on a treadmill to determine
      condylar lift-off from the tibial tray using a 3D-to-2D image-to-model
      registration technique. Correlations between the amount of lift-off and either
      the stress radiograph or the KSS were also analyzed. RESULTS: The mean angle
      measured was 5.9 +/- 2.7 degrees  with varus stress and 5.0 +/- 1.6 degrees  with
      valgus stress. The difference between them was 0.9 +/- 2.8 degrees . Varus-valgus
      laxities, or the differences between them, did not show any statistically
      significant correlation with either component of the KSS (p > 0.05). The average
      amount of femoral condylar lift-off during walking was 1.4 +/- 0.8 mm (medial
      side) and 1.3 +/- 0.6 mm (lateral side). The amount of lift-off did not correlate
      with either varus-valgus laxities or the KSS (p > 0.05). CONCLUSIONS: No
      correlations were found among varus-valgus laxities under static stress in
      extension, femoral condylar lift-off during walking, or patient-reported outcomes
      after well-aligned TKA. This study suggests that small variations in coronal
      laxities do not influence lift-off during walking and the patient-reported
      outcomes. LEVEL OF EVIDENCE: IV.

PMID- 24923690
TI  - Anterior cruciate ligament injury and ankle dorsiflexion.
AB  - PURPOSE: The aim was to study whether the degree of ankle dorsiflexion differs
      between subjects with an anterior cruciate ligament (ACL) injury and uninjured
      controls. Another aim was to study ankle dorsiflexion between the injured and the
      uninjured leg and in addition between women and men with an ACL injury. METHOD:
      Sixty subjects (ACL injury, n = 30 and controls, n = 30) were enroled
      consecutively at two physical therapy settings. Ankle dorsiflexion was measured
      with a goniometer in a standardized way in a weight-bearing lunge position.
      RESULTS: Repeated-measures ANOVA revealed a significant difference (p < 0.001) in
      ankle dorsiflexion between subjects with an ACL injury (mean 41.1 degrees  SD
      5.7) and those without (mean 46.6 degrees  SD 5.3). No difference in ankle
      dorsiflexion was found between the injured leg and the uninjured or between women
      and men with ACL injury. CONCLUSION: The present findings suggest lower degree of
      ankle dorsiflexion in subjects with an ACL injury than in uninjured controls. A
      functional test measuring ankle dorsiflexion with a goniometer may be one way of
      identifying individuals at increased risk of ACL injury. LEVEL OF EVIDENCE:
      Comparative study, Level II.

PMID- 24923691
TI  - Treatment of osteochondral defects of the talus in children.

PMID- 24923693
TI  - A "turn on/off" scorpion biosensor targeting point mutation of SMN genes for
      diagnosis of spinal muscular atrophy.
AB  - A "turn on/off" biosensor for diagnosis of exon 7 of the SMN1 gene was developed
      by employing a "scorpion primer". This scorpion primer was based on the principle
      of fluorescence resonance energy transfer using a fluorophore, a blocker and a
      quencher. It was successfully applied to detect 10 volunteer samples, and not
      only to in vitro testing. 

PMID- 24923692
TI  - Anatomic observation of the running space of the suprascapular nerve at the
      suprascapular notch in the same direction as the nerve.
AB  - PURPOSE: The configuration of suprascapular notch was previously analysed from
      the anteroposterior viewing. However, the approach direction of the suprascapular
      nerve (SSN) to the inlet of the suprascapular notch is consistently craniocaudal
      and mediolateral. We propose a new method to observe the suprascapular notch
      according to the running course of the SSN. We reviewed the anatomic
      characteristics of the suprascapular notch in relation to the nerve. METHODS: In
      30 formalin-fixed cadaveric shoulders, the morphology of the suprascapular notch
      and the attachments of the superior transverse scapular ligament (STSL) were
      examined from both the anteroposterior and the nerve approach direction. The
      dimensions of the opening of the SSN passage were measured. RESULTS: By observing
      from the nerve approach direction, the inlet of the suprascapular notch was
      recognized to be a space-bordered by the medial wall of the coracoid process, the
      deep fascia of subscapularis, and the STSL. The STSL formed a sheet-like
      structure, which ran parallel to the nerve and also to the deep fascia of
      subscapularis. The attachment of the ligament to the coracoid process was located
      at the posteromedial corner rather than the medial side. CONCLUSION: Based on the
      present study, the space between the STSL and deep fascia of the subscapularis
      formed the space for the nerve to run through. As a clinical implication, this
      new method to assess the suprascapular notch in the nerve approach direction
      might develop the imaging techniques for evaluation of SSN entrapment.

PMID- 24923694
TI  - Laparoscopic adjustable gastric banding reduces subcutaneous adipose tissue and
      blood inflammation in nondiabetic morbidly obese individuals.
AB  - BACKGROUND: Significant and sustained excess weight loss (EWL) appears to reduce
      the risk of obesity-related comorbidities (insulin resistance, hyperlipidemia,
      and inflammation), but this has been primarily shown in adult diabetic obese
      patients. We evaluated whether the EWL obtained 3 years after laparoscopic
      adjustable gastric banding (LAGB) improves the metabolic phenotype in nondiabetic
      morbidly obese (NDMO) individuals from south Italy. METHODS: Serum and
      subcutaneous adipose tissue (SAT) samples from 20 obese individuals (median
      BMI=41.5 kg/m(2)) before (T0) and after LAGB (T1) and from 10 controls (median
      BMI=22.8 kg/m(2)) were taken. Serum leptin, adiponectin, C reactive protein
      (CRP), and main analyte levels were evaluated by routine methods or immunoassay.
      In SAT, adipocyte size was measured by hematoxylin/eosin staining, cluster of
      differentiation 68 (CD68) macrophage infiltration marker by immunohistochemistry,
      and adiponectin, adiponectin receptors 1 and 2, and interleukin 6 (IL6) messenger
      RNAs by qRT-PCR. RESULTS: The average EWL was 66.7 %, and CRP, triglycerides,
      hepatic markers, leptin levels, homeostasis model assessment, and the
      leptin/adiponectin ratio were lower (p<0.05) at T1 than at T0. The expression of
      small adipocytes and adiponectin was increased (p<0.05), and inflammation markers
      (CD68 and IL6) decreased (p<0.05) at T1 vs. T0. At linear regression multivariate
      analysis, over 90 % (R (2)=0.905) of EWL (dependent variable) was explained by
      CD68, adiponectinemia, triglyceridemia, CRP, and total protein levels.
      CONCLUSIONS: The EWL obtained 3 years after LAGB resulted in an improvement of
      lipid metabolism and a reduction of inflammation in NDMO patients, thereby
      decreasing the risk of obesity-associated diseases.

PMID- 24923696
TI  - The effect of 22 kHz calls and artificial 38 kHz signals on activity in rats.
AB  - Ultrasonic calls at 22 kHz are emitted by adult rats Rattus norvegicus when
      submissive, after and sometimes before copulation and in aversive situations, but
      the function of these calls, if any, is not known. This study examined the effect
      of 22 kHz calls on the behaviour of individuals. Rats were exposed singly for 5
      min to a tape-recorded test signal; 22 kHz calls or artificial 38 kHz signals or
      tape noise. All rats were exposed to tape noise before and after the test signal.
      Both of the ultrasonic signals, and particularly the 22 kHz calls, decreased
      locomotor activity in rats during replay and for 5 min afterwards. Rats sniffed
      the loudspeaker less during the replay of 22 kHz calls than during the other test
      signals. These results complement others showing that constant frequency
      ultrasound from visual display units and oscilloscopes also depresses activity.
      In natural aggressive situations 22 kHz calls could allow a subordinate to escape
      and prevent the dominant wasting time in pursuit. In the laboratory exposure of
      rats to natural or artificial ultrasound could affect ongoing or subsequent
      behaviour and so be a confounding experimental variable. 

PMID- 24923695
TI  - Consensus report from the 6th International forum for liver MRI using gadoxetic
      acid.
AB  - As the utility of liver-specific magnetic resonance imaging (MRI) increases, it
      is pertinent to optimize and expand protocols to improve accuracy and foster
      evolution of techniques; in turn, positive impacts should be seen in patient
      management. This article reports on the latest expert thinking and current
      evidence in the field of liver-specific MRI, as discussed at the 6(th)
      International Forum for Liver MRI, which was held in Vancouver, Canada in
      September 2012. Topics discussed at this forum described the use of gadoxetic
      acid-enhanced MRI for the assessment of liver function at the segmental level; to
      increase accuracy in the diagnosis of liver metastases; to overcome current
      challenges in patients with cirrhosis, including management of arterial hypo
      /isovascular, hepatobiliary phase hypointense nodules; and the data which would
      be required in order to recommend the use of this modality in hepatocellular
      carcinoma management guidelines. Growing evidence suggests that gadoxetic acid
      enhanced MRI can help to improve the management of patients with a number of
      different liver disorders; however, more data are needed in some areas, and there
      may be a case for developing an interpretation guideline for gadoxetic acid
      enhanced MRI findings to aid standardization.

PMID- 24923697
TI  - Social motivation in Japanese quail coturnix coturnix japonica chicks selected
      for high or low levels of treadmill behaviour.
AB  - Social motivation (as measured by a visually isolated chick's tendency to
      establish visual contact with, move towards and remain in proximity to a group of
      conspecifics) was assessed in lines of Japanese quail which had been selected for
      high (HSR line) or low (LSR line) levels of an index of treadmill behaviour which
      combined the tendency to run towards conspecifics with the tendency to move away
      from them. HSR line chicks peeded sooner and more frequently before establishing
      visual contact with conspecifics and spent more time close to conspecifics after
      visual contact had been established than LSR line chicks. HSR line chicks also
      tended to have shorter latencies to establish visual contact with conspecifics,
      jump more and interact more with conspecifics than LSR chicks. It is suggested
      that these results indicate that selection for treadmill behaviour, which is
      considered to be a measure of social reinstatement tendencies, has influenced
      overall levels of social motivation. Furthermore, it would also appear that the
      phenotypic differences between the HSR and LSR lines are relatively intensive to
      genotype x environment interactions. 

PMID- 24923698
TI  - Response to intruders in female rabbit colonies is related to sex of intruder and
      rank of residents.
AB  - Behavioural reactions to unfamiliar conspecifics of both sexes were studied in
      female domestic rabbits, living in stable unisexual groups. Intrusion caused an
      abrupt increase in the frequency of social investigation and agonistic behaviours
      directed to both intruders and group-mates. Reactions depended on the rank of
      resident females and the sex of the intruder, and were generally more marked in
      the presence of the male than the female intruder. Dominant and sub-dominant
      females investigated the male more than the female intruder; the opposite held
      for subordinate females. In the presence of the female intruder, only dominant
      and subdominant females were aggressive towards the intruder and group-mates. In
      the presence of the male intruder, aggression was directed to the intruder and
      group-mates by dominant females only. They tended to frequently attack sub
      dominants, which in turn fled away from them more often than they did from other
      group-mates. 

PMID- 24923699
TI  - A new pheromone in the ant Pheidole pallidula (Myrmicinae).
AB  - In the dimorphic species Pheidole pallidula, an ethological factor, present on
      the VIIth abdominal sternite attracts ants from short distances and enhances the
      linear speed of those having approached it. Added to poison gland extract, it
      improves the workers' trail following behaviour. This factor is essentially
      presented by minors, majors' sternite having a much weaker ethological effect.
      Several functions and a glandular origin are suggested for this hitherto unknown
      pheromone in Pheidole pallidula. 

PMID- 24923700
TI  - Song syllable variation tolerance and motor theory of song perception: the
      territorial reaction of cirl bunting Emberiza cirlus to homologue syllables.
AB  - The extent of syllable variation tolerance was tested using synthetic homologue
      syllables. A synthetic copy of a common syllable type of cirl bunting Emberiza
      cirlus song was used as control. Homologue syllables, in the same frequency range
      but shorter or longer, were created by multiplying (2/3, 5/3, 7/3) the time scale
      of the control syllable. By this way the specificity of homologue syllables
      inside (2/3) and outside (5/3 and 7/3) the syllable duration range (mean +/- 2
      SD) of the species were tested. Results do not support a hypothesis for syllable
      variation tolerance founded on motor perception theory. Processes free from
      production occur in syllable recognition. 

PMID- 24923701
TI  - Discrimination of group members by laying hens Gallus domesticus.
AB  - Two experiments were performed to test if hens could discriminate between
      conspecifics in learning experiments. In experiment 1, three adult hens were
      trained to discriminate between a member of their own social group and a member
      of a neighbouring group. Only one test bird showed evidence of discrimination
      above conventional levels of significance. In experiment 2, three hens were
      trained to discriminate between two members from their own social group. All test
      birds showed strong evidence of discrimination above conventional levels of
      significance indicating that laying hens are able to discriminate between members
      of their own social group. 

PMID- 24923703
TI  - Tolerability and efficacy of long-term treatment with daptomycin, ceftazidime and
      colistin in a patient with a polymicrobial, multidrug-resistant prosthetic joint
      reinfection: a case report.
AB  - INTRODUCTION: Prosthetic joint infections are severe complications of joint
      implants. Further complications arise when polymicrobial and/or multidrug
      resistant microorganisms are involved. Currently, there are limited data on the
      management of these infections and on the tolerability of long-term treatment
      with daptomycin, ceftazidime and colistin. CASE PRESENTATION: A 55-year-old
      Caucasian woman who had a right hip prosthesis removed 1 year prior because of
      infection was admitted for prosthesis reimplantation. On admission at our
      hospital, anamnesis regarding etiology and management of prosthesis infection was
      not available. On clinical, laboratory findings and imaging studies infection was
      not suspected. A hip prosthesis was reimplanted. At surgery, histopathological
      and microbiological investigations were not taken. Three weeks after
      reimplantation, surgical site infection due to Enterobacter cloacae was diagnosed
      and oral ciprofloxacin was prescribed. Four days later, a periprosthesis fluid
      collection was evidenced and a percutaneous needle aspirate grew Staphylococcus
      epidermidis and S. haemolyticus. Enterobacter genome was also detected from the
      same sample. Teicoplanin and meropenem were added to ciprofloxacin without
      clinical improvement. Moreover, acetabular cup dislocation was documented. She
      underwent prosthesis explantation, debridement, and positioning of an
      antimicrobial mixed spacer. From the intraoperatory cultures S. epidermidis and
      Acinetobacter baumannii were grown. Daptomycin, ceftazidime, colistin and
      rifampin were administered. Four days later, rifampin was stopped due to a
      suspected liver toxicity. While undergoing therapy she presented recurrent
      episodes of wound dehiscence and on the 22nd week of treatment a further surgical
      debridement was performed, upon which the spacer was removed. At this time,
      intraoperative cultures resulted negative. Three months later, after a total of 8
      months, antimicrobials were interrupted. Subsequently, a femoral transcondylar
      traction was positioned, and 3 weeks later a new prosthesis was reimplanted. At
      over 1 year after reimplantation she is well. CONCLUSIONS: Our findings suggest
      that microbiologic investigations are mandatory even when prosthetic joint
      infection is not suspected. Molecular methods for identification of
      microorganisms can be used in addition to conventional cultures especially when
      patients are under antibiotic treatment. Daptomycin, ceftazidime and colistin can
      be administered for several months without side effects. Guidelines specifically
      addressing the diagnosis and the management of polymicrobial, multidrug-resistant
      prosthetic joint infections need to be developed.

PMID- 24923704
TI  - High prevalence of non-alcoholic fatty liver disease in the Chinese - results
      from the Hong Kong liver health census.
AB  - BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) in
      the general Chinese population is not clear, as there have been few large
      population studies focussing on healthy individuals. We aim to determine the
      prevalence and risk factors of NAFLD in a healthy Westernized Chinese population.
      METHODS: This is a prospective cross-sectional study of 2493 volunteers recruited
      from the general population and the Red Cross Transfusion Center in Hong Kong.
      All underwent comprehensive questionnaire survey, blood test, abdominal
      ultrasound and transient elastography. RESULTS: The prevalence of NAFLD was 42%.
      Gender, age, waist circumference, systolic blood pressure, fasting cholesterol
      and glucose levels were significant factors. The relative risk of NAFLD in those
      with high waist circumference, diabetes, hypertension, and hypercholesterolaemia
      was 2.99, 2.01, 1.79 and 1.54 respectively. The degree of steatosis increased
      with levels of fasting glucose, cholesterol, systolic blood pressure and waist
      circumference (all P < 0.001). The optimal waist circumference was found to be 84
      and 74 cm for male and females respectively, with a relative risk of 5.16 for
      those above this limit. In total, 1.2% and 0.002% with NAFLD had advanced liver
      fibrosis and cirrhosis respectively. CONCLUSION: Non-alcoholic fatty liver
      disease was found to be highly prevalent in the Chinese population. Increasing
      levels of risk factors were associated with increasing severity of NAFLD. Lower
      cut-off levels of waist circumference to predict NAFLD should be adopted for
      Chinese population.

PMID- 24923706
TI  - Childhood tuberculosis: A roadmap towards zero deaths.
AB  - 'Every day, more than 200 children under the age of 15 die needlessly from
      tuberculosis (TB) - a disease that is preventable and curable. The World Health
      Organization estimates that as many as 1 in 10 TB cases globally (6-10% of all TB
      cases) are among this age group, but the number could be even higher because many
      children are simply undiagnosed.' Childhood TB is emerging from the shadows. This
      quote comes from the recently launched international roadmap towards zero TB
      deaths in children. We provide a brief update of new developments and remaining
      challenges related to childhood TB, with particular emphasis on the new roadmap. 

PMID- 24923707
TI  - Misclassification in assessment of diabetogenic risk using electronic health
      records.
AB  - PURPOSE: Suspected diabetogenic effects or drug indication may increase testing
      for diabetes mellitus (DM), resulting in measurement bias when evaluating
      diabetogenic drug effects. We sought to evaluate the validity of electronic
      health record data in determining DM risk. METHODS: We used time-dependent Cox
      proportional hazard models within a retrospective cohort design to assess
      associations between use of antihypertensives, statins, atypical antipsychotics,
      and antidepressants, and two endpoints: (i) DM onset defined as fasting blood
      glucose (BG) >=126 mg/dl, random BG >=200 mg/dl, HbA1c >=7.0%, or antidiabetic
      drug initiation; and (ii) first negative DM test. We used Poisson regression to
      assess the influence of these drugs on DM testing rates. Patients aged 35-64
      years enrolled in Kaiser Permanente Northwest between 1997 and 2010 entered the
      cohort at the first negative BG test after >=6 months without manifest DM.
      RESULTS: All drug classes showed significant associations not only with DM onset
      but also with first negative BG test and with DM testing rates. Antipsychotics
      had the greatest diabetogenic risk (adjusted hazard ratio [HR] = 1.73 [1.44
      2.08]), the greatest propensity for a first negative test (adjusted HR = 1.87
      [1.74-2.01]), and the highest testing rate (adjusted rate ratio = 1.76 [1.72
      1.81]. Although renin-angiotensin system blockers and calcium channel blockers
      have shown no diabetogenic risk in clinical trials, both were associated with DM
      (HR = 1.19 [1.12-1.26] and 1.27 [1.17-1.38]), a negative glucose test (1.38 [1.35
      1.41] and 1.24 [1.20-1.28]), and increased testing rates (rate ratio = 1.26 [1.24
      1.27] and 1.27 [1.25-1.28]). CONCLUSION: Caution should be used when diabetogenic
      risk is evaluated using data that rely on DM testing in general practice.

PMID- 24923708
TI  - High-efficiency perovskite solar cells based on the black polymorph of HC(NH2)2
      PbI3.
AB  - Perovskite solar cells with power conversion efficiencies exceeding 16% at AM 1.5
      G one sun illumination are developed using the black polymorph of formamidnium
      lead iodide, HC(NH2)2 PbI3 . Compared with CH3 NH3 PbI3 , HC(NH2 )2 PbI3 extends
      its absoprtion to 840 nm and shows no phase transition between 296 and 423 K.
      Moreover, a solar cell based on HC(NH2 )2 PbI3 exhibits photostability and little
      I-V hysteresis.

PMID- 24923711
TI  - The acoustic behaviour of the bushcricket Tettigonia cantans III. Coprocessing of
      auditory and vibratory information in the central nervous system.
AB  - All the acoustic units in the ventral-nerve cord respond to both sound and
      vibration. Most of them show improved coding abilities when stimulated
      simultaneously with conspecific songs and vibration signals. This is also true
      for habituating neurons. Stridulating tettigoniids produce both airborne sound
      and substrate borne vibration and their simultaneous processing in the central
      nervous system may therefore lead to a better localization of a nearly sound
      source in the biotope. 

PMID- 24923710
TI  - Quantification of left ventricular volumes, mass, and ejection fraction using
      cine displacement encoding with stimulated echoes (DENSE) MRI.
AB  - PURPOSE: To test the hypothesis that magnitude images from cine displacement
      encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) can
      accurately quantify left ventricular (LV) volumes, mass, and ejection fraction
      (EF). MATERIALS AND METHODS: Thirteen mice (C57BL/6J) were imaged using a 7T
      ClinScan MRI. A short-axis stack of cine T2-weighted black blood (BB) images was
      acquired for calculation of LV volumes, mass, and EF using the gold standard sum
      of-slices methodology. DENSE images were acquired during the same imaging session
      in three short-axis (basal, mid, apical) and two long-axis orientations. A custom
      surface fitting algorithm was applied to epicardial and endocardial borders from
      the DENSE magnitude images to calculate volumes, mass, and EF. Agreement between
      the DENSE-derived measures and BB-derived measures was assessed via coefficient
      of variation (CoV). RESULTS: 3D surface reconstruction was completed on the order
      of seconds from segmented images, and required fewer slices to be segmented.
      Volumes, mass, and EF from DENSE-derived surfaces matched well with BB data (CoVs
      <=11%). CONCLUSION: LV mass, volumes, and EF in mice can be quantified through
      sparse (five slices) sampling with DENSE. This consolidation significantly
      reduces the time required to assess both mass/volume-based measures of cardiac
      function and advanced cardiac mechanics.

PMID- 24923712
TI  - Amplitude, latency, and habituation of the electrodermal response to acoustic
      stimuli in the frog.
AB  - The electrodermal response (EDR) of frogs to various acoustic stimuli was
      measured in the form of the skin potential response (SPR). There was no
      correlation between the polarity of the SPR and the intensity of the stimuli.
      When different frequencies were presented at the same intensity, the amplitude of
      the SPR to each was inversely proportional to the sound pressure at which that
      frequency just elicited an SPR. The amplitude of the sound-induced SPR increased
      monotonically with increasing sound pressure. The latency of the SPR decreased
      with increasing intensity of the acoustic stimulus. Acoustic stimuli repeated at
      intervals of 1 and 2 min elicited responses with progressively decreased
      amplitude and increased latency; with 4 min intervals there was little
      habituation. Fatigue participates to only a very slight extent in reducing the
      amplitude of the SPR and increasing its latency. The results are compared with
      the published data on frogs and mammals, including humans. 

PMID- 24923709
TI  - Review of collagen I hydrogels for bioengineered tissue microenvironments:
      characterization of mechanics, structure, and transport.
AB  - Type I collagen hydrogels have been used successfully as three-dimensional
      substrates for cell culture and have shown promise as scaffolds for engineered
      tissues and tumors. A critical step in the development of collagen hydrogels as
      viable tissue mimics is quantitative characterization of hydrogel properties and
      their correlation with fabrication parameters, which enables hydrogels to be
      tuned to match specific tissues or fulfill engineering requirements. A
      significant body of work has been devoted to characterization of collagen I
      hydrogels; however, due to the breadth of materials and techniques used for
      characterization, published data are often disjoint and hence their utility to
      the community is reduced. This review aims to determine the parameter space
      covered by existing data and identify key gaps in the literature so that future
      characterization and use of collagen I hydrogels for research can be most
      efficiently conducted. This review is divided into three sections: (1) relevant
      fabrication parameters are introduced and several of the most popular methods of
      controlling and regulating them are described, (2) hydrogel properties most
      relevant for tissue engineering are presented and discussed along with their
      characterization techniques, (3) the state of collagen I hydrogel
      characterization is recapitulated and future directions are proposed. Ultimately,
      this review can serve as a resource for selection of fabrication parameters and
      material characterization methodologies in order to increase the usefulness of
      future collagen-hydrogel-based characterization studies and tissue engineering
      experiments. 

PMID- 24923713
TI  - Estimation of fear in two lines of the domestic chick: Correlations between
      various methods.
AB  - The assessment of fear is a controversial issue and low levels of correlation
      between different measures have been used to criticise the fear concept. The
      present study assessed fear levels in individual domestic chicks of each of two
      lines, flighty and docile, using four commonly employed methods of estimating
      fear. They were the hole-in-the-wall box, the open field, response to a bell and
      tonic immobility. On the basis of a wide variety of behavioural responses each
      chick was ranked for fearfulness in each of the four tests. The degrees of
      association or correlation between these ranking within lines were then
      calculated. The significant intra-individual correlations found in both lines
      provides some support for the use of these tests as methods of estimating fear,
      at least within the lines used. Differences in the degree or form of fear
      responding between the lines are also discussed in terms of reactions to handling
      and to sudden auditory stimuli. 

PMID- 24923714
TI  - Plumage phenotypes and mate preferences in Japanese quail 2. sexual imprinting.
AB  - Mate selection, with emphasis on early social (sexual imprinting) and subsequent
      long-term social experience, was studied in a randombred population of Japanese
      quail consisting of wildtype (W), redhead (R) and Albino (A) plumage colors.
      Early social experiences involved situations where flocks of the various plumage
      colors were maintained either separately or intermingled. Initial mate
      preferences were determined from a series of paired choice-tests between plumage
      phenotypes. Wildtype and redhead females exhibited no preferences, while albino
      hens preferred albino males. Preferences exhibited by albino males depended on
      sexual imprinting; those with no other experience preferred albinos and redheads
      to wildtypes, whereas those raised with other morphs did not distinguish among
      phenotypes. Redhead and wildtype males while avoiding albino hens, did not
      distinguish between redhead and wildtype hens. Combinations of the plumage color
      social experience flocks (A&R; A&W; R&W) were housed for long-term observations
      of mate selection. Albino hens mated only albino males. Redhead and wildtype hens
      having previous experience with albinos mated more frequently with albino males
      than those lacking such experience. Redhead and wildtype hens showed no
      preference between redhead and wildtype males. Albino males did not distinguish
      among female plumage colors, whereas redhead and wildtype males avoided albino
      hens, and mated equally with redhead and wildtype hens. In a series of
      nonsimultaneous choice trials, redhead and wildtype females were mated
      significantly more than albinos. These results demonstrate the influence of
      genetic mechanisms, sexual imprinting and subsequent long-term social experiences
      on the optimization of mate selection. 

PMID- 24923715
TI  - Studies on tube restraint-induced attack on a metal target by laboratory mice.
AB  - This study examines factors influencing the attack on a metal target by
      laboratory 'TO' strain mice confined within a narrow perspex tube and contrasts
      this form of behaviour with attack seen in less equivocal forms of 'aggression
      test'. The effects of sex, housing condition, reproductive experience, density,
      anosmia and castration (in the male) were systematically examined. This 'model'
      of 'aggression' shows few parallels with social conflict, parental defense and
      electroshock-induced forms of attack as none of the above manipulations
      influenced the level of target biting in this situation. Thus, in spite of claims
      that tube restraint-induced attack may show parallels with intermale aggression,
      the data suggest that it involves a totally different motivation. 

PMID- 24923716
TI  - Reproductive memory for diagonal and nondiagonal patterns in chimpanzees.
AB  - Two male juvenile chimpanzees were trained to reproduce from memory geometric
      patterns composed of lighted cells in a 3 x 3 matrix. In Experiment I, subjects
      reproduced 3-cell horizontal, vertical and diagonal patterns with either 0- or 5
      second delay between stimulus offset and response. Diagonals were more difficult
      and were more affected by delay than were nondiagonal patterns. The sequence of
      response to diagonals was less structured than to nondiagonals. In Experiment II,
      more complex 4-cell patterns were used and, following training, subjects were
      tested for transfer to new patterns. Again, diagonals were more difficult to
      reproduce than nondiagonals. Transfer of training to new patterns requiring
      different motoric responses was successful. Similar to Experiment I, organization
      of responding was greater for nondiagonals than for diagonals. These results are
      discussed with regard to the presence of internal representation of visual
      information in nonhuman primates. 

PMID- 24923717
TI  - Maternal subgrouping in lowland gorillas.
AB  - Mountain gorilla females have been reported to seek out the dominant male and to
      increase the time spent in proximity to him when they are caring for young
      infants. The study examined subgrouping phenomenon in a captive group of lowland
      gorilla mothers. Interaction scores failed to support the position that the male
      is attractive to mothers, or that they seek him out and cluster about him. The
      data indicate instead that the females avoid interacting with the male and rarely
      initiate contact with him. Subgroups and social clustering observed among the
      females is interpreted as preferential contact among mothers. 

PMID- 24923719
TI  - The beta-adrenoceptor agonist isoproterenol rescues acetaminophen-injured livers
      through increasing progenitor numbers by Wnt in mice.
AB  - Acetaminophen (APAP)-induced acute liver injury (AILI) is a major health problem.
      Accumulating evidence suggests that the sympathetic nervous system (SNS)
      regulates neuronal and hematopoietic progenitors. SNS signaling affects hepatic
      progenitor/oval cells (HPCs) and beta-adrenoceptor agonism will expand HPCs to
      reduce AILI. Dopamine beta-hydroxylase-deficient mice (Dbh-/-), lacking
      catecholamine SNS neurotransmitters, isolated HPCs, and immature ductular 603B
      cells were initially used to investigate SNS involvement in HPC physiology.
      Subsequently, control mice were treated with APAP (350 mg/kg) followed by the
      beta-adrenoceptor agonist, isoproterenol (ISO), or the beta-adrenoceptor
      antagonist, propranolol. Mechanistic studies examined effects of non-SNS HPC
      expansion on AILI, involvement of the canonical Wnt/beta-catenin pathway (CWP) in
      the action of ISO on HPC expansion and comparison of ISO with the current
      standard of care, N-acetylcysteine (NAC). Dbh-/- mice lacking catecholamines had
      low HPC numbers, reconstituted by ISO. In vitro, ISO-induced proliferation of
      603B cells was CWP dependent. In control mice, AILI raised HPC numbers, further
      increased by ISO, with attenuation of liver injury. Delayed administration of NAC
      did not, but delayed ISO did, reverse AILI. Propranolol worsened AILI. AILI
      activated the CWP, and ISO enhanced Wnt-ligand production. HPCs were the major
      source of Wnt ligands. Recombinant Wnt3a and ISO-603B-conditioned media, but not
      ISO alone, protected isolated hepatocytes from death, reversed by DKK1-a Wnt
      antagonist. Additionally, tumor-associated weak inducer of apoptosis expanded
      HPCs and protected against AILI. Furthermore, allotransplantation of HPCs from
      APAP+ISO-treated mice to other APAP-injured mice improved AILI, an effect
      antagonized by DKK1. CONCLUSION: SNS catecholamines expand HPCs, which are both
      targets and sources of Wnt ligands. Hepatoprotection by ISO is mediated by para-
      and autocrine effects of Wnt signaling. ISO represents novel pharmacotherapy for
      AILI.

PMID- 24923720
TI  - Incidental magnetic resonance diffusion-weighted imaging-positive lesions are
      rare in neurologically asymptomatic community-dwelling adults.
AB  - BACKGROUND AND PURPOSE: Incidental magnetic resonance diffusion-weighted imaging
      (DWI)-positive lesions, considered to represent small acute infarcts, have been
      detected in patients with cerebral small vessel diseases or cognitive impairment,
      but the prevalence in the community population is unknown. METHODS: DWI sequences
      collected in 793 participants in the Prospective Urban Rural Epidemiological
      (PURE) study were reviewed for DWI lesions consistent with small acute infarcts.
      RESULTS: No DWI-positive lesions were detected (0%, 95% confidence interval, 0
      0.5). CONCLUSIONS: DWI-positive lesions are rare in an asymptomatic community
      population. The prevalence of DWI-positive lesions in the community seems to be
      lower than in patients with cerebral amyloid angiopathy, intracerebral
      hemorrhage, or cognitive impairment.

PMID- 24923721
TI  - Features predictive of brain arteriovenous malformation hemorrhage: extrapolation
      to a physiologic model.
AB  - BACKGROUND AND PURPOSE: Although there is generally thought to be a 2% to 4% per
      annum rupture risk for brain arteriovenous malformations (bAVMs), there is no way
      to estimate risk for an individual patient. METHODS: In this retrospective study,
      patients were eligible who had nidiform bAVMs and underwent detailed pretreatment
      diagnostic cerebral angiography at our medical center from 1996 to 2006. All
      patients had superselective microcatheter angiography, and films were reviewed
      for the purpose of this project. Patient demographics, clinical presentation, and
      angioarchitectural characteristics were analyzed. A univariate analysis was
      performed, and angioarchitectural features with potential physiological
      significance that showed at least a trend toward significance were added to a
      multivariate logistic regression model. RESULTS: One hundred twenty-two bAVMs met
      criteria for study entry. bAVMs with single venous drainage anatomy were more
      likely to present with hemorrhage. In addition, patients with multiple draining
      veins and a venous stenosis reverted to a risk similar to those with 1 draining
      vein, whereas those with multiple draining veins and without stenosis had
      diminished association with hemorrhage presentation. Those bAVMs with associated
      aneurysms were more likely to present with hemorrhage. These findings were robust
      in both univariate and multivariate models. CONCLUSIONS: The results of this
      article lead to the first physiological, internally consistent model of
      individual bAVM hemorrhage risk, where 1 draining vein, venous stenosis, and
      associated aneurysms increase risk.

PMID- 24923722
TI  - Strategic planning to reduce the burden of stroke among veterans: using
      simulation modeling to inform decision making.
AB  - BACKGROUND AND PURPOSE: Reducing the burden of stroke is a priority for the
      Veterans Affairs Health System, reflected by the creation of the Veterans Affairs
      Stroke Quality Enhancement Research Initiative. To inform the initiative's
      strategic planning, we estimated the relative population-level impact and
      efficiency of distinct approaches to improving stroke care in the US Veteran
      population to inform policy and practice. METHODS: A System Dynamics stroke model
      of the Veteran population was constructed to evaluate the relative impact of 15
      intervention scenarios including both broad and targeted primary and secondary
      prevention and acute care/rehabilitation on cumulative (20 years) outcomes
      including quality-adjusted life years (QALYs) gained, strokes prevented, stroke
      fatalities prevented, and the number-needed-to-treat per QALY gained. RESULTS: At
      the population level, a broad hypertension control effort yielded the largest
      increase in QALYs (35,517), followed by targeted prevention addressing
      hypertension and anticoagulation among Veterans with prior cardiovascular disease
      (27,856) and hypertension control among diabetics (23,100). Adjusting QALYs
      gained by the number of Veterans needed to treat, thrombolytic therapy with
      tissue-type plasminogen activator was most efficient, needing 3.1 Veterans to be
      treated per QALY gained. This was followed by rehabilitation (3.9) and targeted
      prevention addressing hypertension and anticoagulation among those with prior
      cardiovascular disease (5.1). Probabilistic sensitivity analysis showed that the
      ranking of interventions was robust to uncertainty in input parameter values.
      CONCLUSIONS: Prevention strategies tend to have larger population impacts, though
      interventions targeting specific high-risk groups tend to be more efficient in
      terms of number-needed-to-treat per QALY gained.

PMID- 24923723
TI  - Randomized controlled trial on hemifield eye patching and optokinetic stimulation
      in acute spatial neglect.
AB  - BACKGROUND AND PURPOSE: Right hemisphere stroke patients frequently experience
      spatial neglect, a severe lack of awareness for contralesional hemispace.
      Although neglect counts among the strongest predictors for poor functional
      outcome after stroke, there is no established therapy, particularly not for the
      acute stage. METHODS: In a randomized controlled trial, we compared the combined
      treatment of hemifield eye patching and repetitive optokinetic stimulation in
      acute stroke patients with neglect to the spontaneous course. Outcome measures
      were a neuropsychological test battery for neglect as well as scales of
      functional independence and clinical impairment. Outcomes were assessed at
      baseline (day 1), post treatment (day 8), and at 1-month follow-up (day 30).
      RESULTS: Final analysis included 21 acute right hemisphere stroke patients with
      neglect (23 enrolled, 2 lost to follow-up) allocated either to the treatment (1
      week hemifield eye patching and daily sessions of optokinetic stimulation, n=11)
      or the control group (no neglect-specific treatment, n=10). At baseline, both
      groups did not differ in neuropsychological test performance, clinical
      impairment, or functional disability. At the post treatment session, both groups
      had improved in all these measures, and results were stable or further improved
      at follow-up. However, there was no significant difference in this change between
      the treatment and the control group. CONCLUSIONS: An early intervention of
      combined hemifield eye patching and optokinetic stimulation in acute stroke
      patients with spatial neglect has no additive effect to the spontaneous remitting
      course of the disorder. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01617343.

PMID- 24923724
TI  - Impact of diffusion-weighted imaging Alberta stroke program early computed
      tomography score on the success of endovascular reperfusion therapy.
AB  - BACKGROUND AND PURPOSE: In acute ischemic stroke patients treated by intravenous
      thrombolysis, a diffusion-weighted imaging (DWI) Alberta Stroke Program Early
      Computed Tomography Score (ASPECTS) is an independent factor of functional
      outcomes. Our aim was to assess the impact of pretreatment DWI-ASPECTS on
      outcomes after endovascular therapy, with a specific emphasis on recanalization.
      METHODS: We analyzed data collected between April 2007 and March 2013 in a
      prospective clinical registry of acute ischemic stroke patients treated by
      endovascular approach. Every patient with a documented internal carotid artery or
      middle cerebral artery occlusion who underwent an acute DWI-MRI before treatment
      was eligible for this study. The primary outcome was a favorable outcome defined
      by modified Rankin Scale of 0 to 2 at 90 days. RESULTS: Two hundred ten patients
      were included and median DWI-ASPECTS was 7 (interquartile range, 4-8). DWI
      ASPECTS>=5 was the optimal threshold to predict a favorable outcome (area under
      the curve=0.69; sensitivity, 90%; specificity, 38%). In a multivariate analysis
      including confounding variables, the adjusted odds ratio for favorable outcomes
      associated with a DWI-ASPECTS of >=5 was 5.06 (95% confidence interval, 1.86
      13.77; P=0.002). Nonetheless, the occurrence of a complete recanalization was
      associated with an increased rate of favorable outcomes in patients with DWI
      ASPECTS under 5 (50% versus 3%, P<0.001). CONCLUSIONS: DWI-ASPECTS>=5 seems to be
      the optimal threshold to predict favorable outcomes among patients undergoing
      endovascular reperfusion within 6 hours. Selected patients with a DWI-ASPECTS of
      <5 may still benefit when a complete reperfusion is achieved.

PMID- 24923725
TI  - The 2015 Hyogo Framework for Action: cautious optimism.

PMID- 24923726
TI  - The prevalence of anxiety and depression in people with age-related macular
      degeneration: a systematic review of observational study data.
AB  - BACKGROUND: Comorbid mental health problems have been shown to have an adverse
      effect on the quality of life of people with common eye disorders. This study
      aims to assess whether symptoms of anxiety and/or depression are more prevalent
      in people with age-related macular degeneration (AMD) than in people without this
      condition. METHODS: A systematic search of electronic databases (Medline, CINAHL,
      EMBASE, PsycINFO) from inception to February 2012 was conducted to identify
      studies of AMD populations which measured symptoms of anxiety and/or depression.
      Reference checking of relevant articles was also performed. Data on the study
      setting, prevalence and how anxiety and depression were measured were extracted
      from the papers. Critical appraisal was performed using the Critical Appraisal
      Skills Programme (CASP) tools. RESULTS: A total of 16 papers were included in the
      review, from an original search result of 597. The prevalence estimates, taken
      from nine cross-sectional and cohort studies, ranged from 15.7%-44% for
      depressive symptoms and 9.6%-30.1% for anxiety symptoms in people with AMD. The
      seven case-control studies found that people with AMD were more likely to
      experience symptoms of depression compared with those without AMD, but not more
      likely to experience symptoms of anxiety. CONCLUSIONS: Overall, the evidence
      suggests that symptoms of depression are more prevalent amongst AMD populations
      than anxiety symptoms. The heterogeneity of the studies included in this review
      means that it is difficult to draw strong conclusions as to the true estimates of
      depression and anxiety symptoms in AMD populations and prevented formal meta
      analysis. Further research which specifies clinical anxiety and gives clear
      definitions as to the type of AMD being investigated is required.

PMID- 24923727
TI  - A neighborhood-based approach to population health in the pediatric medical home.
AB  - Health care reform is increasingly focused on population health outcomes. Local
      strategies low-income neighborhoods could connect every newborn to a medical home
      and create a platform to link them with other health-promoting community
      resources. (1) To improve connections to the medical home for infants from one
      low-income neighborhood (2) To increase the number of families enrolled in a
      local home visiting program, and (3) To improve communication between medical
      staff and home visitors. The study was conducted in a neighborhood with 550
      births per year and median household income of $27,000. Quality improvement
      methods were used to test: (1) newborn registry in the medical home, (2)
      proactive outreach by nursing staff, (3) standardized protocol for enrolling
      families in home visiting, and (4) coordination of care between medical home and
      home visitors. Outcomes were timeliness of well child care and enrollment in home
      visiting. Time series analyses compared patients from the intervention
      neighborhood with a demographically similar neighborhood. Mean age at newborn
      visit decreased from 14.4 to 10.1 days of age. Attendance at 2- and 4-month well
      child visits increased from 68 to 79% and 35 to 59 %, respectively. Rates did not
      improve for infants from the comparison neighborhood. Confirmed enrollment in
      home visiting increased. After spread to 2 more clinics, 43 % of infants in the
      neighborhood were reached. Neighborhood-based newborn registries, proactive
      nursing outreach, and collaboration with a home visiting agency aligned multiple
      clinics in a low-income neighborhood to improve access to health-promoting
      services. 

PMID- 24923728
TI  - Cancer survival among First Nations people of Ontario, Canada (1968-2007).
AB  - We aimed to compare cancer survival in Ontario First Nations people to that in
      other Ontarians for five major cancer types: colorectal, lung, cervix, breast and
      prostate. A list of registered or "Status" Indians in Ontario was used to create
      a cohort of over 140,000 Ontario First Nations people. Cancers diagnosed in
      cohort members between 1968 and 2001 were identified from the Ontario Cancer
      Registry, with follow-up for death until December 31st, 2007. Flexible parametric
      modeling of the hazard function was used to compare the survival experience of
      the cohort to that of other Ontarians. We considered changes in survival from the
      first half of the time period (1968-1991) to the second half (1992-2001). For
      other Ontarians, survival had improved over time for every cancer site. For the
      First Nations cohort, survival improved only for breast and prostate cancers; it
      either declined or remained unchanged for the other cancers. For cancers
      diagnosed in 1992 or later, all-cause and cause-specific survival was
      significantly poorer for First Nations people diagnosed with breast, prostate,
      cervical, colorectal (male and female) and male lung cancers as compared to their
      non-First Nations peers. For female lung cancer, First Nations women appeared to
      have poorer survival; however, the result was not statistically significant.
      Ontario's First Nations population experiences poorer cancer survival when
      compared to other Ontarians and strategies to reduce these inequalities must be
      developed and implemented. 

PMID- 24923729
TI  - Simplified submission.

PMID- 24923730
TI  - Antiarrhythmic effect of tamoxifen on the vulnerability induced by
      hyperthyroidism to heart ischemia/reperfusion damage.
AB  - Hyperthyroidism, known to have deleterious effects on heart function, and is
      associated with an enhanced metabolic state, implying an increased production of
      reactive oxygen species. Tamoxifen is a selective antagonist of estrogen
      receptors. These receptors make the hyperthyroid heart more susceptible to
      ischemia/reperfusion. Tamoxifen is also well-known as an antioxidant. The aim of
      the present study was to explore the possible protective effect of tamoxifen on
      heart function in hyperthyroid rats. Rats were injected daily with 3,5,3'
      triiodothyronine at 2mg/kg body weight during 5 days to induce hyperthyroidism.
      One group was treated with 10mg/kg tamoxifen and another was not. The protective
      effect of the drug on heart rhythm was analyzed after 5 min of coronary occlusion
      followed by 5 min reperfusion. In hyperthyroid rats not treated with tamoxifen,
      ECG tracings showed post-reperfusion arrhythmias, and heart mitochondria isolated
      from the ventricular free wall lost the ability to accumulate and retain matrix
      Ca(2+) and to form a high electric gradient. Both of these adverse effects were
      avoided with tamoxifen treatment. Hyperthyroidism-induced oxidative stress caused
      inhibition of cis-aconitase and disruption of mitochondrial DNA, effects which
      were also avoided by tamoxifen treatment. The current results support the idea
      that tamoxifen inhibits the hypersensitivity of hyperthyroid rat myocardium to
      reperfusion damage, probably because its antioxidant activity inhibits the
      mitochondrial permeability transition.

PMID- 24923731
TI  - All sex steroids are made intracellularly in peripheral tissues by the mechanisms
      of intracrinology after menopause.
AB  - Following the arrest of estradiol secretion by the ovaries at menopause, all
      estrogens and all androgens in postmenopausal women are made locally in
      peripheral target tissues according to the physiological mechanisms of
      intracrinology. The locally made sex steroids exert their action and are
      inactivated intracellularly without biologically significant release of the
      active sex steroids in the circulation. The level of expression of the steroid
      forming and steroid-inactivating enzymes is specific to each cell type in each
      tissue, thus permitting to each cell/tissue to synthesize a small amount of
      androgens and/or estrogens in order to meet the local physiological needs without
      affecting the other tissues of the organism. Achieved after 500 million years of
      evolution, combination of the arrest of ovarian estrogen secretion, the
      availability of high circulating levels of DHEA and the expression of the
      peripheral sex steroid-forming enzymes have permitted the appearance of menopause
      with a continuing access to intratissular sex steroids for the individual
      cells/tissues without systemic exposure to circulating estradiol. In fact, one
      essential condition of menopause is to maintain serum estradiol at biologically
      inactive (substhreshold) concentrations, thus avoiding stimulation of the
      endometrium and risk of endometrial cancer. Measurement of the low levels of
      serum estrogens and androgens in postmenopausal women absolutely requires the use
      of MS/MS-based technology in order to obtain reliable accurate, specific and
      precise assays. While the activity of the series of steroidogenic enzymes can
      vary, the serum levels of DHEA show large individual variations going from barely
      detectable to practically normal "premenopausal" values, thus explaining the
      absence of menopausal symptoms in about 25% of women. It should be added that the
      intracrine system has no feedback elements to adjust the serum levels of DHEA,
      thus meaning that women with low DHEA activity will not be improved without
      external supplementation. Exogenous DHEA, however, follows the same intracrine
      rules as described for endogenous DHEA, thus maintaining serum estrogen levels at
      substhreshold or biologically inactive concentrations. Such blood concentrations
      are not different from those observed in normal postmenopausal women having high
      serum DHEA concentrations. Androgens, on the other hand, are practically all made
      intracellularly from DHEA by the mechanisms of intracrinology and are always
      maintained at very low levels in the blood in both pre- and postmenopausal women.
      Proof of the importance of intracrinology is also provided, among others, by the
      well-recognized benefits of aromatase inhibitors and antiestrogens used
      successfully for the treatment of breast cancer in postmenopausal women where all
      estrogens are made locally. Each medical indication for the use of DHEA, however,
      requires clinical trials performed according to the FDA guidelines and the best
      rules of clinical medicine. 

PMID- 24923732
TI  - Premature adrenarche: etiology, clinical findings, and consequences.
AB  - Adrenarche means the morphological and functional change of the adrenal cortex
      leading to increasing production of adrenal androgen precursors (AAPs) in mid
      childhood, typically at around 5-8 years of age in humans. The AAPs
      dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the best
      serum markers of adrenal androgen (AA) secretion and adrenarche. Normal ACTH
      secretion and action are needed for adrenarche, but additional inherent and
      exogenous factors regulate AA secretion. Inter-individual variation in the timing
      of adrenarche and serum concentrations of DHEA(S) in adolescence and adulthood
      are remarkable. Premature adrenarche (PA) is defined as the appearance of
      clinical signs of androgen action (pubic/axillary hair, adult type body odor,
      oily skin or hair, comedones, acne, accelerated statural growth) before the age
      of 8 years in girls or 9 years in boys associated with AAP concentrations high
      for the prepubertal chronological age. To accept the diagnosis of PA, central
      puberty, adrenocortical and gonadal sex hormone secreting tumors, congenital
      adrenal hyperplasia, and exogenous source of androgens need to be excluded. The
      individually variable peripheral conversion of circulating AAPs to biologically
      more active androgens (testosterone, dihydrotestosterone) and the androgen
      receptor activity in the target tissues are as important as the circulating AAP
      concentrations as determinants of androgen action. PA has gained much attention
      during the last decades, as it has been associated with small birth size, the
      metabolic and polycystic ovarian syndrome (PCOS), and thus with an increased risk
      for type 2 diabetes and cardiovascular diseases in later life. The aim of this
      review is to describe the known hormonal changes and their possible regulators in
      on-time and premature adrenarche, and the clinical features and possible later
      health problems associating with PA. 

PMID- 24923733
TI  - Steroid dimers-in vitro cytotoxic and antimicrobial activities.
AB  - The in vitro cytotoxic activity of previously synthesized steroid dimers with
      different spacer group (sulfide, trithiolane ring or phosphorotrithioate) and the
      substituent at C-17 position was tested for their possible effects against
      following human tumor cell lines: cervical adenocarcinoma (HeLa), chronic
      myelogenous leukemia (K562) and two human breast cancer cell lines (MDA-MB-361
      and MDA-MB-453). These compounds, applied at micromolar concentrations, exhibited
      cytotoxic activity of different intensity (compared with cisplatin as a control),
      modality and selectivity in these malignant cell lines. The best activity against
      all four cell cancer lines was exhibited by dimer-sulfides. All screened
      compounds exerted concentration-dependent cytotoxic activity against leukemia
      K562 cells. The compounds which exerted the most pronounced cytotoxic action
      exhibited notably higher cytotoxic activities against K562, HeLa and MDA-MB-453
      cells in comparison to resting and PHA-stimulated PBMC, pointing to a significant
      selectivity in their antitumor actions. Examination of the mechanisms of
      cytotoxicity on leukemia K562 cells revealed pro-apoptotic action of each of the
      investigated compounds applied at concentrations 2IC50. The most prominent pro
      apoptotic action was exhibited by dimer-sulfide of cholest-4-en-3-one.
      Furthermore, almost all of the tested compounds at IC50 concentrations induced G1
      phase cell cycle arrest in K562 cells. Antimicrobial activity against Gram
      positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp
      Artemia salina, were evaluated. There was no antibacterial activity. The best
      antifungal activity was exhibited against Saccharomyces cerevisiae by dimers
      linked with trithiolane ring, indicating a selective activity of investigated
      compounds. 

PMID- 24923734
TI  - Cell proliferation and modulation of interaction of estrogen receptors with
      coregulators induced by ERalpha and ERbeta agonists.
AB  - The aim of the present study was to investigate modulation of the interaction of
      the ERalpha and ERbeta with coregulators in the ligand responses induced by
      estrogenic compounds. To this end, selective ERalpha and ERbeta agonists were
      characterized for intrinsic relative potency reflected by EC50 and maximal
      efficacy towards ERalpha and ERbeta mediated response in ER selective reporter
      gene assays, and subsequently tested for induction of cell proliferation in T47D
      ERbeta cells with variable ERalpha/ERbeta ratio, and finally for ligand dependent
      modulation of the interaction of ERalpha and ERbeta with coregulators using the
      MARCoNI assay, with 154 unique nuclear receptor coregulator peptides derived from
      66 different coregulators. Results obtained reveal an important influence of the
      ERalpha/ERbeta ratio and receptor selectivity of the compounds tested on
      induction of cell proliferation. ERalpha agonists activate cell proliferation
      whereas ERbeta suppresses ERalpha mediated cell proliferation. The responses in
      the MARCoNI assay reveal that upon ERalpha or ERbeta activation by a specific
      agonist, the modulation of the interaction of the ERs with coregulators is very
      similar indicating only a limited number of differences upon ERalpha or ERbeta
      activation by a specific ligand. Differences in the modulation of the interaction
      of the ERs with coregulators between the different agonists were more pronounced.
      Based on ligand dependent differences in the modulation of the interaction of the
      ERs with coregulators, the MARCoNI assay was shown to be able to classify the ER
      agonists discriminating between different agonists for the same receptor, a
      characteristic not defined by the ER selective reporter gene or proliferation
      assays. It is concluded that the ultimate effect of the model compounds on
      proliferation of estrogen responsive cells depends on the intrinsic relative
      potency of the agonist towards ERalpha and ERbeta and the cellular ERalpha/ERbeta
      ratio whereas differences in the modulation of the interaction of the ERalpha and
      ERbeta with coregulators contribute to the ligand dependent responses induced by
      estrogenic compounds. 

PMID- 24923736
TI  - Heat-shock proteins and acute ischaemic kidney injury.
AB  - The incidence of acute kidney injury due to ischaemia-reperfusion injury (IRI) is
      rising but effective treatments and preventative approaches are currently
      lacking. IRI is also an inevitable consequence of kidney transplantation and
      significantly contributes to delayed graft function. Heat-shock proteins (Hsps)
      are highly conserved and ubiquitously expressed molecular chaperones that help
      maintain and restore normal cellular function in the kidney following IRI. Hsp70
      is one of the most frequently studied Hsps because of potential cytoprotective
      properties and attractiveness as a therapeutic target. However, the protective
      properties of Hsp70 in renal IRI are not fully understood and putative modes of
      protection include correction of protein conformation, cytoskeletal
      stabilisation, anti-inflammatory effects, requirement in autophagy, anti
      apoptotic properties, influence over macrophage phenotype and stimulation of
      regulatory T cells. Significant clinical interest has been generated about the
      possibility of applying pharmacological agents to induce Hsp70 and prevent renal
      IRI, but prior to this, an increased mechanistic understanding of the protective
      nature of Hsp70 is needed. In particular, further investigation of Hsp expression
      on inflammatory cell behaviour is required as this could lead to the development
      of new therapeutic strategies for enhancing recovery following renal IRI and
      broaden the range of these therapies to a wider group of patients.

PMID- 24923735
TI  - Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T
      cell and antibody outputs.
AB  - Epitope content plays a critical role in determining T-cell and antibody
      responses to vaccines, biomaterials, and protein therapeutics, but its effects
      are nonlinear and difficult to isolate. Here, molecular self-assembly is used to
      build a vaccine with precise control over epitope content, in order to finely
      tune the magnitude and phenotype of T helper and antibody responses. Self
      adjuvanting peptide nanofibers are formed by co-assembling a high-affinity
      universal CD4+ T-cell epitope (PADRE) and a B-cell epitope from Staphylococcus
      aureus at specifiable concentrations. Increasing the PADRE concentration from
      micromolar to millimolar elicited bell-shaped dose-responses that are unique to
      different T-cell populations. Notably, the epitope ratios that maximize T
      follicular helper and antibody responses differed by an order of magnitude from
      those that maximized Th1 or Th2 responses. Thus, modular materials assembly
      provides a means of controlling epitope content and efficiently skewing the
      adaptive immune response in the absence of exogenous adjuvant; this approach may
      contribute to the development of improved vaccines and immunotherapies. 

PMID- 24923737
TI  - Metabolic syndrome after pediatric liver transplantation.
AB  - Half of adult liver transplantation (LT) recipients develop metabolic syndrome,
      but the prevalence after childhood LT remains unknown. We conducted a national
      cross-sectional study of all living patients who had undergone LT between 1987
      and 2007 at an age less than 18 years. We gathered information on blood pressure,
      body composition, serum lipids, glucose metabolism, and histological liver fat
      content. The diagnostic criteria for metabolic syndrome of the American Heart
      Association and the International Diabetes Federation were used. After a median
      post-LT follow-up time of 12 years, half of all patients had no components of
      metabolic syndrome. The prevalence of overweight/obesity was 20%, and the
      prevalence of hypertension was 24%. Serum triglycerides were high in 9%, and high
      density lipoprotein levels were low in 23%. Fasting glucose levels were impaired
      in 14%, but none had diabetes. Altogether, 9 patients (14%) had metabolic
      syndrome. Moderate liver steatosis found in protocol liver biopsy samples was
      associated with the accumulation of metabolic syndrome features (P = 0.01). No
      significant associations were found between immunosuppressive medications and
      metabolic syndrome. In conclusion, the prevalence of metabolic syndrome after
      childhood LT is similar to the prevalence in the general population of the same
      age. Guidelines for the general population, therefore, seem valid for the
      prevention and treatment of metabolic syndrome after pediatric LT as well.

PMID- 24923738
TI  - Three-dimensional scapular motion during arm elevation is altered in women with
      fibromyalgia.
AB  - BACKGROUND: The core feature of fibromyalgia is pain, which may play a role in
      various mechanisms that might lead to alterations in shoulder kinematics.
      Alterations in muscle activity and presence of tender points in the shoulder
      girdle have already been described in this population; however there is lack of
      evidence on three-dimensional scapular motion in women with fibromyalgia.
      METHODS: Forty women with fibromyalgia and 25 healthy women (control group)
      matched in terms of age, weight and height, took part in this study. Three
      dimensional scapular kinematics of the dominant arm were collected during
      elevation and lowering of the arm in the sagittal and scapular planes. Pain was
      evaluated by the Visual Analogue Scale and the Numerical Pain Rating Scale. Group
      comparisons were performed with one-way ANOVA for pain and two-way ANOVA for the
      kinematic variables (scapular internal/external rotation, upward/downward
      rotation and anterior/posterior tilt), with group and humeral elevation angle as
      categorical factors. Significance level was set at P<0.05. FINDINGS: Fibromyalgia
      women presented higher pain scores (P<0.001) than the control group. Fibromyalgia
      women also presented greater scapular upward rotation (P<0.001, both planes) and
      greater scapular posterior tilt (P<0.001, both planes) than the control group.
      INTERPRETATION: Women with fibromyalgia present greater scapular upward rotation
      and posterior tilt in the resting position and during arm elevation and lowering
      of the arm in sagittal and scapular planes. These alterations may be a
      compensatory mechanism to reduce pain during arm movement.

PMID- 24923739
TI  - Adenocarcinoma of the pancreas: Does prognosis depend on mode of lymph node
      invasion?
AB  - BACKGROUND: Lymph node (LN) invasion in pancreatic ductal adenocarcinoma (PDAC)
      is the most important prognostic factor after surgical resection. The mechanisms
      of LN invasion include lymphatic spreading and/or direct extension from the main
      tumor. However, few studies have assessed the impact of these different patterns
      of invasion on prognosis. PATIENTS AND METHODS: Pathologic reports of pancreatic
      resections for PDAC from 1997 to 2007 were retrospectively analyzed. The mode of
      LN invasion was defined as follows: standard lymphatic metastases (S), contiguous
      from the main tumor (C) and standard with extracapsular invasion (EI). Clinical
      outcomes were compared according to the mode of invasion and the number of
      invaded LN. RESULTS: 306 patients were reviewed. Median age at resection was 61
      years (range, 34-81). Eighty seven patients were N- (28.9%) and 214 were N+
      (71.1%). Of the N+ patients, 195 (91.1%) were S+, 35 (16.3%) were C+, and 24
      (12.3% of the S+ patients) were EI+. Median survival in N+ patients was lower
      than in N- patients (29 vs. 57 months, p < 0.001). In patients without standard
      involvement, C+ patients (n = 19) had worse survival than C- patients (n = 47)
      (34 vs. 57 months, p = 0.037). In S+ patients, C status was correlated with
      prognosis when the number of LN S+ was <2 (p = 0.07). EI status had no influence
      on prognosis. On multivariate analysis, only perineural invasion (p = 0.02) and
      LN ratio (p = 0.042) were independent prognostic factors. CONCLUSION: Direct
      invasion of LN by the tumor is predictive of reduced survival, but has little
      impact compared to standard LN involvement and perineural invasion.

PMID- 24923740
TI  - A phoenix of clinical toxinology: white-tailed spider (Lampona spp.) bites. A
      case report and review of medical significance.
AB  - The Australian white-tailed spiders ("WTS"; Lamponidae: notably Lampona
      cylindrata &Lampona murina) have a continuing reputation on Internet sites as a
      cause of skin ulceration, labelled "necrotic arachnidism", despite an increasing
      number of peer-reviewed publications debunking this reputation, with >135
      confirmed cases now reported without any evidence of necrosis. We present here a
      case of confirmed WTS bite in a 42-year old male, followed for over a month, with
      photos of bite site signs and no development of skin ulceration/necrosis. The
      patient was initially alarmed by information on the Internet suggesting local
      necrosis would result from the bite. We discuss the evolution of knowledge about
      bites by the WTS, and the persistence of misconceptions about their factually
      mild medical significance. 

PMID- 24923741
TI  - BMP4 promotes SSEA-1(+) hUC-MSC differentiation into male germ-like cells in
      vitro.
AB  - OBJECTIVES: Recent studies have demonstrated that primordial germ cells (PGC) can
      be differentiated from human umbilical cord mesenchymal stem cells (hUC-MSCs),
      and embryonic stem cells (ESCs) in vitro. Nevertheless, efficiencies were low and
      unstable. Here, whether hUC-MSCs can be induced to differentiate into germ-like
      cells with the aid of bone morphogenetic protein (BMP4) was investigated.
      MATERIALS AND METHODS: Human umbilical cord mesenchymal stem cells were freshly
      isolated and cultured with BMP4. SSEA-1(+/-) cells were purified using magnetic
      activated cell sorting (MACS) from the hUC-MSCs, and further induced with BMP4.
      Quantitative real-time PCR (qRT-PCR) and immunofluorescence analysis were used to
      determine PGC and germ-like cell-specific markers. RESULTS: Human umbilical cord
      mesenchymal stem cells differentiated into SSEA-1(+) spherical PGC-like cells
      efficiently with 12.5 ng/ml BMP4. qRT-PCR and immunofluorescence analysis
      demonstrated that SSEA-1(+) cells expressed higher levels of PGC-specific markers
      than SSEA-1(-) cells. Furthermore, SSEA-1(+) cells were induced with BMP4 to
      differentiate into STRA8, SCP3, DMRT1 and PLZF-positive male germ-like cells, and
      some sperm-like cells were obtained by 7-14 days after induction. CONCLUSION:
      These results suggest that SSEA-1(+) hUC-MSCs can differentiate into male germ
      like cells in the presence of BMP4. This study provides an efficient protocol to
      study germ-cell development using hUC-MSCs.

PMID- 24923743
TI  - Alterations in the release calls of six European anura (amphibia) after partial
      or total extirpation of the vocal cords.
AB  - In the interior of the larynx of Ranidae there are two sturdy vocal cords. The
      Bufonidae have more delicate vocal cords, and in addition paired cushions of
      tissue anterior to the cords and paired folds posterior to the cords. In the
      three ranids Rana esculenta, Rana ridibunda and Rana temporaria, partial or total
      extirpation of the vocal cords results in loss of voice or atypical release
      calls. In such remnants of calls as are retained, the frequency composition is
      little affected, whereas the intensity is always greatly reduced. The most severe
      impairment is evident in the formation of sound pulses and in the rhythmicity of
      the pulse sequence. In the three bufonids Bufo bufo, Bufo calamita and Bufo
      viridis loss of voice is a less common result of the various operations than in
      the ranids. The most marked deterioration follows removal of all or part of the
      vocal cords. The tissue cushions and the posterior folds participate, along with
      the vocal cords, in production of the release calls. Post-operative alterations
      in the release calls are therefore quite variable. 

PMID- 24923742
TI  - Biopsy-negative, varicella zoster virus (VZV)-positive giant cell arteritis,
      zoster, VZV encephalitis and ischemic optic neuropathy, all in one.
AB  - A 72-year-old man developed clinical features of giant cell arteritis (GCA) and
      ipsilateral ophthalmic-distribution zoster, followed within 2 weeks by VZV
      encephalitis and 2 months later by ischemic optic neuropathy. Temporal artery
      biopsy was histopathologically negative for GCA, but contained VZV antigen and
      VZV DNA in multiple non-contiguous (skip) areas. The collective clinical and
      laboratory findings revealed a remarkably close temporal association of zoster,
      multifocal VZV vasculopathy with temporal artery infection, biopsy-negative VZV
      positive GCA and VZV encephalitis.

PMID- 24923744
TI  - Behavioural and morphological effects of testosterone and gonadotropins in the
      young male domestic duck (Anas platyrhynchos L.).
AB  - Young male domestic ducks 20-72 days old were successively injected with two
      hormonal preparations. The first hormone treatment included males injected with
      testosterone propionate (TP), human chorionic gonadotropin (HCG), pregnant mare
      serum (PMS), control oil injected males (C) and males injected with TP and
      submitted at the same time to a permanent intense light. During the second
      hormonal treatment all males except controls were injected with TP. Almost no
      behavioural effects were observed in any group of males following the first
      treatment. The second one, however, induced intense social display and sexual
      behaviour in the four TP-injected groups. Some qualitative and quantitative
      differences were found between groups according to the first hormone treatment to
      which they had been submitted. This suggests a possible role of gonadotropic
      hormones in the control of social behaviour in ducks. Experimental data
      supporting this hypothesis are briefly reviewed and discussed. 

PMID- 24923745
TI  - Ontogenetic development of conditioned food aversion in chickens.
AB  - Development of conditioned food aversion (CFA) was studied in 25-, 35-, and 45
      day Leghorn chicks. Food-deprived birds had 10-min access to normal food on days
      1 and 2, and to green coloured food CS on day 3. Injection of LiCl (0.15 M, 3-4%
      body weight) administered 10 min after CS on day 3 served as the US. Control
      groups were injected with the same volume of saline. Retention was tested on day
      4 in three 3-min presentations of normal food alternating with two presentations
      of green food. Number of pecks and amount of food consumed were measured.
      Significant neophobic rejection of green food was observed in 25- but not in 35-
      and 45-day-old control birds. Neophobia in the youngest chicks was further
      accentuated by CFA which could be observed in pure form in the 45-day-old
      experimental group. Comparison of pecking rate and food intake showed that CFA in
      younger birds was accomplished predominantly by inhibition of pecking, and in
      older birds also by reduction of peck volume. It is concluded that protection
      against poisoning in chickens shifts between 25 and 45 days of posthatching age
      from neophobia to CFA. 

PMID- 24923746
TI  - Selective facilitative effect of post-trial reticular stimulation in
      discriminative learning in the rat.
AB  - Ninety-eight Sprague-Dawley rats, implanted with electrodes in the mesencephalic
      tegmentum (reticular activating system, RAS) served as subjects in two
      experiments. In the first experiment (n = 42) we investigated the effects of a
      RAS stimulation (5 MU A, 300 Hz, 90 sec in duration) on the acquisition of a
      positively reinforced light-dark discrimination in a T-maze. In the second
      experiment (n = 56) the reinforcement and the treatment were dissociated by
      comparing the effects of the RAS stimulation administered after correct or
      incorrect choices, during the same discrimination task. In the two experiments,
      despite large differences in learning conditions, the results show a considerable
      learning facilitation by administering the RAS stimulation immediately after each
      trial. This facilitation does not seem to be due to an interaction between
      reinforcement and stimulation, since the results of experiment 2 show the maximum
      facilitation in animals stimulated after each (non-reinforced) error, compared to
      subjects stimulated after each (reinforced) correct choice. These results are
      discussed both in terms of consolidation processes and in terms of comparison of
      the cue values of S(+) and S(-) in a discriminative learning situation. 

PMID- 24923747
TI  - Acquisition of avoidance reaction in rats with different social experience in
      youth.
AB  - The acquisition of both active and passive avoidance response, the extinction of
      the former and the retention of the long-term memory trace of the latter were
      studied in 30- and 90-day-old male rats of the Wistar strain. The rats were in 3
      groups which had had a different history between 15 and 30 days of age: (1)
      normally weaned rats lived from birth in a cage together with mother and
      siblings, i.e. under usual laboratory breeding conditions; (2) prematurely weaned
      rats lived under the same conditions for the first 15 days; after this period,
      their mother was removed from the cage; (3) community-reared rats had the same
      history up to 15 days of age; then they began to live in a community (5 connected
      cages) in contact with both young and adult rats from other cages. Ninety- day
      old male rats acquired an active avoidance response at the same rate irrespective
      of their history in youth but 30-day-old rats were relatively slower if they had
      been prematurely weaned. Among both normally and prematurely weaned 30-day-old
      rats, the extinction was slower than in community-reared rats of the same age.
      Passive avoidance response was acquired by all rats at the same rate irrespective
      of their history and age. The long- term memory trace was always more stable in
      adult rats than in young ones. 

PMID- 24923748
TI  - The interaction between conditioned fish and naive schools of juvenile carp
      (Cyprinus carpio, pisces).
AB  - In a circular experimental pool the behaviour of trained juvenile carp placed in
      naive schools of different size and of different behavioural motivation was
      studied. It could be shown that the time the trained fish needed to arrive at the
      feeding place was much shorter when it swam in a habituated school than in a
      frightened one. This is discussed as a result of the conflict between the
      conditioned reaction and the various levels of mutual attraction. In the same
      manner the time elapsing from CS until the interruption of the movement of gills
      and fins also varied. The percentage of schooling companions which followed the
      trained fish to the feeding place diminished with growing school size. Six to ten
      fish may be the upper limit that one carp can guide. 

PMID- 24923751
TI  - Performance enhancement of capacitive-coupling dual-gate ion-sensitive field
      effect transistor in ultra-thin-body.
AB  - Recently, thin-film transistor based-ISFETs with the dual-gate (DG) structures
      have been proposed, in order to beat the Nernst response of the standard ISFET,
      utilizing diverse organic or inorganic materials. The immutable Nernst response
      can be dramatically transformed to an ultra-sensing margin, with the capacitive
      coupling arisen from the DG structure. In order to advance this platform, we here
      embedded the ultra-thin body (UTB) into the DG ISFET. The UTB of 4.3 nm serves to
      not only increase its sensitivity, but also to strongly suppress the leakage
      components, leading to a better stability of the DG ISFET. In addition, we first
      provide a comprehensive analysis of the body thickness effects especially how the
      thick body can render the degradation in the device performance, such as
      sensitivity and stability. The UTB DG ISFET will allow the ISFET-based biosensor
      platform to continue enhancement into the next decade.

PMID- 24923752
TI  - The canine hepatic progenitor cell niche: molecular characterisation in health
      and disease.
AB  - Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver
      that contributes to liver regeneration when replication of mature hepatocytes is
      insufficient. In this study, laser microdissection was used to isolate HPC niches
      from the livers of healthy dogs and dogs with lobular dissecting hepatitis (LDH),
      in which HPCs are massively activated. Gene expression of HPC, hepatocyte and
      biliary markers was determined by quantitative reverse transcriptase PCR.
      Expression and localisation of selected markers were further studied at the
      protein level by immunohistochemistry and immunofluorescent double staining in
      samples of normal liver and liver from dogs with LDH, acute and chronic
      hepatitis, and extrahepatic cholestasis. Activated HPC niches had higher gene
      expression of the hepatic progenitor markers OPN, FN14, CD29, CD44, CD133, LIF,
      LIFR and BMI1 compared to HPCs from normal liver. There was lower expression of
      albumin, but activated HPC niches were positive for the biliary markers SOX9,
      HNF1beta and keratin 19 by immunohistochemistry and immunofluorescence. Laminin,
      activated stellate cells and macrophages are abundant extracellular matrix and
      cellular components of the canine HPC niche. This study demonstrates that the
      molecular and cellular characteristics of canine HPCs are similar to rodent and
      human HPCs, and that canine HPCs are distinctively activated in different types
      of liver disease.

PMID- 24923753
TI  - Diagnosis of canine gastric adenocarcinoma using squash preparation cytology.
AB  - Adenocarcinoma is the most common gastric tumour in dogs. Clinical signs and
      laboratory results are often non-specific, with histopathological examination of
      gastric biopsies being required to reach a definitive diagnosis. Use of cytology
      would potentially shorten the time to diagnosis and allow early interventional
      measures to be implemented. However, there are relatively few studies of the
      cytological features of gastric samples. The present study was designed to
      investigate whether cytology might be useful for diagnosis of canine gastric
      adenocarcinomas and to evaluate the performance of squash preparation cytology
      for this purpose. Squash preparations of gastric biopsies from 94 dogs were
      reviewed to determine the presence or absence of specific cytological features
      associated with adenocarcinomas and to compare findings with the results of
      histopathological examination of gastric biopsies. The presence of signet ring
      cells, microvacuolation, cellular pleomorphism and single cell distribution of
      epithelial cells were positively associated with a diagnosis of gastric
      adenocarcinoma. Combined evaluation (parallel testing) for the presence of signet
      ring cells and microvacuolation demonstrated excellent results for recognition of
      adenocarcinomas. Cytological examination of squash preparations from gastric
      biopsies and identification of signet ring cells and cytoplasmic vacuolation can
      allow rapid and reliable diagnosis of canine gastric adenocarcinomas.

PMID- 24923754
TI  - Feline parvovirus infection and associated diseases.
AB  - Feline panleukopenia, caused by the single-stranded DNA virus feline parvovirus
      (FPV), is a highly contagious and often lethal disease of cats and other Felidae.
      FPV, but also canine parvovirus (CPV) can be isolated from both healthy and
      diseased cats. In Germany, CPV was detected in only approximately 10% of feline
      samples, but in Southeast Asia, reports estimated that up to approximately 80% of
      diseased cats were infected with CPV. Infection spreads rapidly, especially in
      cells with high mitotic activity, such as bone marrow, lymphoid tissue and
      intestinal crypt cells. Anorexia, vomiting, diarrhoea, neutropenia and
      lymphopenia are common in clinically affected cases. In utero or neonatal
      infection can result in cerebellar hypoplasia. Depending on the severity of
      clinical signs, mortality ranges from 25 to 100%. Effective vaccination and
      thorough disinfection are of the utmost importance in the prevention of disease
      transmission in multi-cat households and animal shelters. If clinical signs
      develop, supportive treatment should be commenced. The efficacy of feline
      recombinant interferon and FPV antibodies has not been clearly demonstrated.
      Commercially available vaccines should induce protective immunity when
      administered according to current guidelines. Recent studies suggest that in some
      kittens, maternally derived antibodies (MDA) can persist for much longer than has
      been previously recognised. FPV serum antibody tests are available, but
      protection status needs to be interpreted with caution in kittens with MDA and a
      negative titre in adult cats does not necessarily denote lack of protection.

PMID- 24923755
TI  - Impact of tetrodotoxin application and lidocaine supplementation on equine
      jejunal smooth muscle contractility and activity of the enteric nervous system in
      vitro.
AB  - By blocking the enteric nervous system (ENS) using tetrodotoxin (TTX), previous
      studies have documented the contractility-enhancing (CE) effects of lidocaine in
      equine intestinal smooth muscle (SM) at the level of SM cells and/or interstitial
      cells of Cajal (ICC). The present study examined the impact of ENS deactivation
      on CE lidocaine effects, and investigated the effects of lidocaine on ENS
      activity. TTX application did not affect the CE effects of lidocaine, indicating
      that these were not mediated by TTX-sensitive sodium channels. Application of TTX
      or >=100 mg/L lidocaine reduced ENS activity. Although such concentrations of
      lidocaine exceed therapeutic blood concentrations, tissue concentrations may be
      higher with the potential to reduce ENS activity and impair intestinal motility
      in vivo. Improved understanding of underlying mechanisms is relevant for
      therapeutic use of lidocaine in horses with postoperative ileus.

PMID- 24923756
TI  - Prevalence of upper respiratory pathogens in four management models for unowned
      cats in the Southeast United States.
AB  - Upper respiratory infection (URI) is a pervasive problem in cats and impacts the
      capacity and cost of sheltering programs. This study determined the pattern of
      respiratory pathogens in cats with and without clinical signs of URI in four
      different models for managing unowned cats, namely, (1) short-term animal
      shelters (STS), (2) long-term sanctuaries (LTS), (3) home-based foster care
      programs (FCP), and (4) trap-neuter-return programs for community cats (TNR).
      Conjunctival and oropharyngeal swabs from 543 cats, approximately half of which
      showed clinical signs of URI, were tested for feline herpes virus-1 (FHV), feline
      calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica, Mycoplasma felis,
      and canine influenza virus by real-time PCR. FHV (59%, 41%) and B. bronchiseptica
      (33%, 24%) were more prevalent in both clinically affected and nonclinical cats,
      respectively, in STS than other management models. FCV (67%, 51%) and M. felis
      (84%, 86%) were more prevalent in LTS than any other management model. Clinically
      affected cats in FCP were more likely to carry FHV (23%, 6%), C. felis (24%,
      10%), or M. felis (58%, 38%) than were nonclinical cats. Clinically affected cats
      in TNR were more likely to carry FCV (55%, 36%) or C. felis (23%, 4%) than were
      nonclinical cats. The prevalence of individual pathogens varied between different
      management models, but the majority of the cats in each model carried one or more
      respiratory pathogens regardless of clinical signs. Both confined and free
      roaming cats are at risk of developing infectious respiratory disease and their
      health should be protected by strategic vaccination, appropriate antibiotic
      therapy, effective biosecurity, feline stress mitigation, and alternatives to
      high-density confinement.

PMID- 24923757
TI  - Recognition of lameness: man versus machine.

PMID- 24923759
TI  - Programming of the development of tumor-promoting neutrophils by mesenchymal
      stromal cells.
AB  - BACKGROUND/AIMS: Neutrophils obtain immunosuppressive function during tumor
      development, yet the mechanisms are largely unknown. This study explored whether
      and how mesenchymal stromal cells (MSCs), the key component of tumor
      microenvironment, regulate the suppressive function of neutrophils. METHODS:
      Immunosuppressive function of neutrophils was evaluated by T cell proliferation
      assay and 4T1 breast tumor model; molecular mechanisms were explored by
      transcriptional profiling, Real-time RT-PCR, arginase activity assay, and iNOS
      inhibition experiments. RESULTS: After being cocultured with MSCs primed by TNF
      alpha (TNF-MSCs), CD11b(+)Ly6G(+) neutrophils isolated from bone marrow of normal
      mice or spleen of tumor-bearing mice obtained immunosuppressive function to
      inhibit T cell proliferation in vitro, and to enhance 4T1 tumor progression in
      vivo. Moreover, arginase activity and expression of iNOS, saa3, some cytokines
      and chemokines and their receptors, were upregulated in neutrophils after co
      culture with TNF-MSCs. Inhibition of iNOS activity attenuated the suppressive
      effect of TNF-MSC pre-cocultured neutrophils on T cell proliferation. CONCLUSION:
      MSCs program neutrophils into an immunosuppressive and tumor-promoting phenotype.

PMID- 24923758
TI  - Red cell distribution width predicts mortality in infective endocarditis.
AB  - BACKGROUND: Infective endocarditis (IE) is associated with significant morbidity
      and mortality. Red cell distribution width (RDW) is a recently recognized
      biomarker of adverse outcome in a number of acute and chronic conditions. AIM: To
      investigate the relationship between RDW and 1-year survival in patients with IE.
      METHODS: Clinical records from two tertiary centres were used to analyze data
      from patients with definite IE. Clinical, echocardiographic and biochemical
      variables were evaluated along with RDW. One-year survival status after index
      hospitalization was identified for each patient. RESULTS: One hundred consecutive
      patients (mean age 47.8+/-16.7 years; 61% men) with definite IE were enrolled.
      According to receiver operating characteristic curve analysis, the optimal RDW
      cut-off value for predicting mortality was 15.3% (area under the curve 0.70;
      P=0.001). Forty-one patients (41%) died within 1 year; of these, 88% had RDW
      results>15.3%. Univariate Cox proportional-hazards analysis showed that
      RDW>15.3%, heart failure, renal failure, cardiac abscess, severe valvular
      regurgitation and presence of dehiscence were associated with increased
      mortality. Multivariable Cox proportional-hazards analysis revealed that renal
      failure (hazard ratio [HR] 3.21, 95% confidence interval [CI] 1.35-7.59;
      P=0.008), heart failure (HR 2.77, 95% CI 1.1-6.97; P=0.03) and RDW>15.3% (HR
      3.07, 95% CI 1.06-8.86; P=0.03) were independent predictors of mortality in
      patients with IE. CONCLUSION: According to our results, mortality is high in
      patients with IE. RDW is a promising biomarker for predicting 1-year survival
      rates in these patients.

PMID- 24923760
TI  - Antipsychotic polypharmacy in schizophrenia patients in China and its association
      with treatment satisfaction and quality of life: findings of the third national
      survey on use of psychotropic medications in China.
AB  - OBJECTIVE: This study examined the use, demographic and clinical correlates of
      antipsychotic polypharmacy (APP) and its associations with treatment satisfaction
      and quality of life (QOL) in schizophrenia patients in China. METHOD: A total of
      4239 patients in 45 nationwide Chinese psychiatric hospitals/centers were
      interviewed in 2012 in the third cross-sectional study, with the first two having
      been conducted in 2002 and 2006. Patients' socio-demographic and clinical
      characteristics, including psychopathology, side effects, satisfaction with
      treatment and QOL, were recorded using a standardized protocol and data
      collection procedure. RESULTS: The proportion of APP prescriptions in 2012 was
      34.2%, which was significantly higher than the frequency of APP in 2002 (26.1%)
      and 2006 (26.4%) (p<0.001). Of patients on APP, 91.1% received two
      antipsychotics, 8.6% received three and 0.3% received four or more
      antipsychotics. Multiple logistic regression analyses revealed that compared to
      those on antipsychotic monotherapy, patients on APP and their families had lower
      satisfaction with treatment, had higher QOL in the mental domain, younger age of
      onset, more side effects, higher doses of antipsychotics and were more likely to
      receive first-generation antipsychotics and less likely to receive
      benzodiazepines (total R (2)=0.31, p<0.001). CONCLUSIONS: APP was found in about
      one in three schizophrenia patients. The prevalence of APP seems to have been
      increasing since 2002. Considering the increased frequency of drug-induced side
      effects and the patients' and their relatives' dissatisfaction with antipsychotic
      treatment, further examination of the rationale and appropriateness of APP and
      its alternatives is warranted.

PMID- 24923761
TI  - Suicide attempt and externalizing behaviours in posttraumatic stress disorder
      (PTSD): possible role of the activating effect of antidepressants.

PMID- 24923762
TI  - Selective TGF-beta1/ALK inhibitor improves neuronal differentiation of mouse
      embryonic stem cells.
AB  - The transforming growth factor-beta1 (TGF-beta1), a polypeptide member of the TGF
      beta superfamily, has myriad cellular functions, including cell fate
      differentiation. We hypothesized that suppression of TGF-beta1 signaling would
      improve the efficacy of neuronal differentiation during embryoid body (EB)
      development. In this study, mouse embryonic stem cells (ESCs) were allowed to
      differentiate into their neuronal lineage, both with, and without the TGF-beta1
      inhibitor (A83-01). After 8 days of EB suspension culture, the samples were
      examined by morphological analysis, immunocytochemistry and immunohistochemistry
      with pluripotent (Oct4, Sox2) and neuronal specific markers (Pax6, NeuN). The
      alteration of gene expressions during EB development was determined by
      quantitative RT-PCR. Our results revealed that the TGF-beta1/ALK inhibitor
      potentially suppressed pluripotent gene (Oct4) during a rapidly up-regulation of
      neuronal associated genes including Sox1 and MAP2. Strikingly, during EB
      development, the expression of GFAP, the astrocyte specific gene, remarkably
      decreased compared to the non-treated control. This strategy demonstrated the
      beneficial function of TGF-beta1/ALK inhibitor that rapidly and uniformly drives
      cell fate alteration from pluripotent state toward neuronal lineages. 

PMID- 24923763
TI  - Effects of electroacupuncture on ethanol-induced impairments of spatial learning
      and memory and Fos expression in the hippocampus in rats.
AB  - It is well established that alcohol impairs spatial learning and memory. Here, we
      investigated the effects of electroacupuncture (EA) at ST36 or nonacupoint on
      ethanol-induced learning and memory impairment and the expression of Fos in the
      hippocampus. Ethanol (5g/kg) was administered intragastrically once a day for 5
      consecutive days; 2Hz EA was administered immediately after ethanol exposure.
      After a 2-day ethanol abstinence, for 6 consecutive days, the rats were submitted
      to Morris water maze training. Probe trials were performed on 1 day after the
      final training session. We also applied immunohistochemistry to detect Fos
      positive nuclei in the hippocampus. We found that 5-day ethanol exposure markedly
      decreased spatial learning and memory abilities in the Morris water maze task as
      indicated by escape latency and time in the target quadrant. EA treatment
      shortened the time of reaching platform and increased times traveled in the
      target quadrant (P<0.05). Animals administered with ethanol emitted significantly
      fewer Fos expression in the hippocampal CA1 area. EA increased Fos expression in
      the hippocampal CA1 area. Significant correlations were obtained between Fos
      protein expression in CA1 and time in the target quadrant. Altogether, these
      results suggest that EA protects against ethanol-induced impairments of spatial
      learning and memory, which may be involved in the hippocampal CA1 area. EA
      treatment may provide a novel nonpharmacological strategy for ethanol-induced
      learning and memory impairment. 

PMID- 24923764
TI  - Ribosomally encoded antibacterial proteins and peptides from Pseudomonas.
AB  - Members of the Pseudomonas genus produce diverse secondary metabolites affecting
      other bacteria, fungi or predating nematodes and protozoa but are also equipped
      with the capacity to secrete different types of ribosomally encoded toxic
      peptides and proteins, ranging from small microcins to large tailocins. Studies
      with the human pathogen Pseudomonas aeruginosa have revealed that effector
      proteins of type VI secretion systems are part of the antibacterial armamentarium
      deployed by pseudomonads. A novel class of antibacterial proteins with structural
      similarity to plant lectins was discovered by studying antagonism among plant
      associated Pseudomonas strains. A genomic perspective on pseudomonad
      bacteriocinogeny shows that the modular architecture of S pyocins of P.
      aeruginosa is retained in a large diversified group of bacteriocins, most of
      which target DNA or RNA. Similar modularity is present in as yet poorly
      characterized Rhs (recombination hot spot) proteins and CDI (contact-dependent
      inhibition) proteins. Well-delimited domains for receptor recognition or
      cytotoxicity enable the design of chimeric toxins with novel functionalities,
      which has been applied successfully for S and R pyocins. Little is known
      regarding how these antibacterials are released and ultimately reach their
      targets. Other remaining issues concern the identification of environmental
      triggers activating these systems and assessment of their ecological impact in
      niches populated by pseudomonads.

PMID- 24923766
TI  - Direct detection for G6PD Bangkok and G6PD Bangkok Noi mutations in the families
      with chronic nonspherocytic hemolytic anemia (CNSHA).

PMID- 24923765
TI  - Five-membered heteroaromatic ring fused-pyrimidine derivatives: design,
      synthesis, and hedgehog signaling pathway inhibition study.
AB  - A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives
      including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines,
      thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines
      have been identified to be potent inhibitors of hedgehog signaling pathway. The
      synthesis and SAR of these compounds are described. Among this new series of
      hedgehog signaling pathway inhibitors, most compounds exhibited significant
      inhibitory activity compared to vismodegib, indicating that the five-membered
      heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among
      the currently reported structural skeletons for hedgehog signaling pathway
      inhibitors, deserving more exploration and further investigation. 

PMID- 24923767
TI  - Reassignment of the land tortoise haemogregarine Haemogregarina fitzsimonsi Dias
      1953 (Adeleorina: Haemogregarinidae) to the genus Hepatozoon Miller 1908
      (Adeleorina: Hepatozoidae) based on parasite morphology, life cycle and
      phylogenetic analysis of 18S rDNA sequence fragments.
AB  - SUMMARY Research was undertaken to clarify the true taxonomic position of the
      terrestrial tortoise apicomplexan, Haemogregarina fitzsimonsi (Dias, 1953). Thin
      blood films were screened from 275 wild and captive South African tortoises of 6
      genera and 10 species between 2009-2011. Apicomplexan parasites within films were
      identified, with a focus on H. fitzsimonsi. Ticks from wild tortoises, especially
      Amblyomma sylvaticum and Amblyomma marmoreum were also screened, and sporogonic
      stages were identified on dissection of adult ticks of both species taken from H.
      fitzsimonsi infected and apparently non-infected tortoises. Parasite DNA was
      extracted from fixed, Giemsa-stained tortoise blood films and from both fresh and
      fixed ticks, and PCR was undertaken with two primer sets, HEMO1/HEMO2, and
      HepF300/HepR900, to amplify parasite 18S rDNA. Results indicated that
      apicomplexan DNA extracted from tortoise blood films and both species of tick had
      been amplified by one or both primer sets. Haemogregarina  fitzsimonsi 18S rDNA
      sequences from tortoise blood aligned with those of species of Hepatozoon, rather
      than those of species of Haemogregarina or Hemolivia. It is recommended therefore
      that this haemogregarine be re-assigned to the genus Hepatozoon, making
      Hepatozoon fitzsimonsi (Dias, 1953) the only Hepatozoon known currently from any
      terrestrial chelonian. Ticks are its likely vectors.

PMID- 24923768
TI  - Peritoneal dialysis outcomes after temporary haemodialysis for peritonitis-
      influence on current practice.

PMID- 24923769
TI  - Drugs in the elderly with chronic kidney disease: beware of potentially
      inappropriate medications.

PMID- 24923770
TI  - Label free high throughput screening for apoptosis inducing chemicals using time
      lapse microscopy signal processing.
AB  - Label free time-lapse microscopy has opened a new avenue to the study of time
      evolving events in living cells. When combined with automated image analysis it
      provides a powerful tool that enables automated large-scale spatiotemporal
      quantification at the cell population level. Very few attempts, however, have
      been reported regarding the design of image analysis algorithms dedicated to the
      detection of apoptotic cells in such time-lapse microscopy images. In particular,
      none of the reported attempts is based on sufficiently fast signal processing
      algorithms to enable large-scale detection of apoptosis within hours/days without
      access to high-end computers. Here we show that it is indeed possible to
      successfully detect chemically induced apoptosis by applying a two-dimensional
      linear matched filter tailored to the detection of objects with the typical
      features of an apoptotic cell in phase-contrast images. First a set of recorded
      computational detections of apoptosis was validated by comparison with apoptosis
      specific caspase activity readouts obtained via a fluorescence based assay. Then
      a large screen encompassing 2,866 drug like compounds was performed using the
      human colorectal carcinoma cell line HCT116. In addition to many well known
      inducers (positive controls) the screening resulted in the detection of two
      compounds here reported for the first time to induce apoptosis. 

PMID- 24923771
TI  - Key concepts in consumer and community engagement: a scoping meta-review.
AB  - BACKGROUND: Although consumer and community engagement (CCE) in health care is
      receiving increasing attention, research and practice in this area are hampered
      by the variability of concepts and terminology commonly employed. This scoping
      meta-review aims to identify key CCE concepts and examine terminology used to
      describe them. METHODS: In a scoping meta-review, an extensive list of 47 phrases
      and 11 Medical Subject Headings (MeSH) was used to undertake a comprehensive and
      systematic search in PubMed Central, Embase, EBM reviews, CINAHL, APAPsycNET, and
      Scopus. RESULTS: 59 systematic reviews met the selection criteria and were
      included in the final analysis. The analysis identified nine different concepts
      related to CCE: shared decision making, self-management, CCE in health care
      systems, community-based health promotion, providing access to health care,
      rehabilitation, participation in research, collaboration in research design and
      conduct, and peer support. The identified concepts differ from each other in many
      aspects including the aim of the activity, the role of consumers and the type of
      professionals' involvement. Each concept was described by a range of terms, with
      some terms shared by different concepts. In addition, two overlapping concepts of
      patient-centeredness and patient empowerment were recognised. CONCLUSIONS: This
      study describes CCE-related key concepts and provides new insight into their
      relationship with different CCE-related terms. Identification of key CCE-related
      concepts and terms will be useful to focus future studies and initiatives and
      enhance production of CCE-related evidence.

PMID- 24923772
TI  - Multiple roles of the PGE2 -EP receptor signal in vascular permeability.
AB  - BACKGROUND AND PURPOSE: PGE2 is a major prostanoid that regulates inflammation by
      stimulating EP1-4 receptors. However, how PGE2 induces an initial inflammatory
      response to vascular hyper-permeability remains unknown. Here we investigated the
      role of the PGE2 -EP receptor signal in modulating vascular permeability both in
      vivo and in vitro. EXPERIMENTAL APPROACH: We used a modified Miles assay and
      intravital microscopy to examine vascular permeability in vivo. Endothelial
      barrier property was assessed by measuring transendothelial electrical resistance
      (TER) in vitro. KEY RESULTS: Local administration of PGE2 , an EP2 or EP4
      receptor agonist into FVB/NJcl mouse ear skin caused vascular leakage, indicated
      by dye extravasation. Intravital microscopy and laser Doppler blood-flow imaging
      revealed that these treatments dilated peripheral vessels and increased local
      blood flow. Pretreatment with the vasoconstrictor phenylephrine inhibited the
      PGE2 -induced blood flow increase and vascular leakage. In contrast to the EP2
      and EP4 receptor agonists, administration of an EP3 receptor agonist suppressed
      vascular leakage without altering vascular diameter or blood flow. In isolated
      HUVECs, the EP3 receptor agonist elevated TER and blocked thrombin-induced
      dextran passage. Inhibiting PKA restored the hypo-permeability induced by the EP3
      receptor agonist. CONCLUSIONS AND IMPLICATIONS: Activation of the PGE2 -EP2 or 
      EP4 receptor signal induces vasodilatation in mural cells, resulting in increased
      local blood flow and hyper-permeability. In contrast, activation of the PGE2 -EP3
      receptor signal induces a cAMP-dependent enhancement of the endothelial barrier,
      leading to hypo-permeability. We provide the first evidence that endothelial
      cells and mural cells cooperate to modulate vascular permeability.

PMID- 24923773
TI  - Immunosuppressive medication adherence in kidney transplant patients.
AB  - OBJECTIVES: To assess the degree of immunosuppressive medication adherence in
      kidney transplant patients (KTPs) and to determine if there is a difference in
      the rate of adherence to tacrolimus (Tac), cyclosporine (CsA) and sirolimus
      (Sir). SUBJECTS AND METHODS: From a total of 63 KTPs treated at the Clinic of
      Nephrology, Clinical Centre Nis, Serbia, 60 participated in the study by
      responding to questionnaires. They were divided into the adherence group (n = 43)
      and the nonadherence group (n = 17) according to their degree of adherence which
      was measured using a validated survey form, the simplified medication adherence
      questionnaire. The KTP adherence to the different immunosuppressive regimens
      (Tac, CsA and Sir) was compared. Statistical analysis was performed using the
      Student t test. RESULTS: Adherence was observed in 43 (71.7%) patients, and only
      17 (28.3%) did not follow the prescribed therapy. The estimated glomerular
      filtration rate was significantly lower in the nonadherence group (38.52 +/-
      18.22 ml/min) than in the adherence group (52.43 +/- 16.91 ml/min, p < 0.05).
      With regard to the Tac level, a significant difference was also found between the
      adherers and the nonadherers (6.30 +/- 2.06 vs. 5.0 +/- 1.52 ng/ml, p < 0.05).
      CONCLUSION: The KTPs in this study demonstrated a high level of adherence.
      Nonadherence was associated with worse graft function and a lower Tac level.
      Knowledge about the degree of adherence could help the early identification of
      nonadherent patients and the development of strategies to improve this.

PMID- 24923774
TI  - Long-term evaluation of orbital rhabdomyosarcoma in children.
AB  - BACKGROUND: Orbital rhabdomyosarcoma (ORMS) is associated with an excellent
      survival rate greater than 85%, and is considered to be a favourable site for
      this tumour. Treatment is based on combination chemotherapy together with best
      local therapy, sometimes surgery but more often radiation therapy. Local therapy
      is associated with frequent and potentially severe late sequelae. DESIGN:
      Retrospective hospital single-centre analysis. PARTICIPANTS: Eighty-two patients
      treated in Institut Curie, Paris. METHODS: To define long-term status of
      survivors after localized ORMS, patients treated between 1975 and 2010 were
      analysed. MAIN OUTCOME MEASURES: Clinical structural and functional orbital, and
      general sequelae. RESULTS: Median age at diagnosis was 6 years (range: 8 months
      19 years), and median follow up was 8.5 years (range: 7 months-24 years). The 5
      year globe conservation rate was 90.4%. Ophthalmic dysfunction was present in 79%
      of patients. Impaired visual acuity (VA), was present in 62% of patients; 38% of
      them had severe visual disability with VA < 6/60. Late effects on orbitofacial
      structure were present in 39.8% of patients. Ocular or palpebral sequelae were
      present in 79% of survivors, mainly cataract (42%), ocular surface lesions such
      as keratoconjunctivitis (40%) and eyelid abnormalities (29%). General late
      effects were rare. CONCLUSIONS: These data suggest that ocular and orbital late
      effects are frequent after treatment of ORMS, indicating the need for systematic
      long-term ophthalmologic follow up of these patients. Radiation therapy is an
      important part of the total burden of therapy.

PMID- 24923775
TI  - A systems biology approach to study the biology characteristics of esophageal
      squamous cell carcinoma by integrating microRNA and messenger RNA expression
      profiling.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors.
      The aim of this study was to investigate the biology characteristics of ESCC by
      analyzing microRNA and mRNA expression profile. We used BRB-array tools to
      analyze the deregulated microRNA and mRNA between esophageal squamous cell
      carcinomas and paired normal adjacent tissues. We used miRTrail and protein
      protein interaction methods to explore the related pathways and networks of
      deregulated microRNA and mRNA. By combining the results of pathways and networks,
      we found that the deregulated microRNA and their deregulated target mRNA are
      enriched in the following pathways: DNA replication, cell cycle, ECM-receptor
      interaction, focal adhesion, mismatch repair, and pathways in cancer. The results
      showed that many deregulated microRNAs and mRNAs may play a vital role in the
      pathogenesis of ESCC, and the systems biology approach is very helpful to explore
      molecular mechanism of ESCC. 

PMID- 24923776
TI  - Retraction. Further pieces of evidence to the pulmonary origin of sevoflurane
      escaping to the operating room during general anaesthesia.

PMID- 24923777
TI  - Mitogenomic sequences effectively recover relationships within brush-footed
      butterflies (Lepidoptera: Nymphalidae).
AB  - BACKGROUND: Mitogenomic phylogenies have revealed well-supported relationships
      for many eukaryote groups. In the order Lepidoptera, 113 species mitogenomes had
      been sequenced (May 14, 2014). However, these data are restricted to ten of the
      forty-three recognised superfamilies, while it has been challenging to recover
      large numbers of mitogenomes due to the time and cost required for primer design
      and sequencing. Nuclear rather than mitochondrial genes have been preferred to
      reconstruct deep-level lepidopteran phylogenies, without seriously evaluating the
      potential of entire mitogenomes. Next-generation sequencing methods remove these
      limitations by providing efficiently massive amounts of sequence data. In the
      present study, we simultaneously obtained a large number of nymphalid butterfly
      mitogenomes to evaluate the utility of mitogenomic phylogenies by comparing
      reconstructions to the now quite well established phylogeny of Nymphalidae.
      RESULTS: We newly obtained 30 nymphalid mitogenomes via pyrosequencing on the
      Roche 454 GS Junior system, and combined these sequences with publicly accessible
      data to provide a 70-taxa dataset covering 37 genes for a 15,495 bp alignment.
      Polymorphic sites were not homogeneously distributed across the gene. Two gene
      regions, nad6 and 3' end of nad5, were most variable, whereas the cox1 and 5'
      ends of rrnL were most conserved. Phylogenetic relationships inferred by two
      likelihood methods were congruent and strongly supported (>0.95 posterior
      probability; ML bootstrap >85%), across the majority of nodes for multiple
      partitioning strategies and substitution models. Bayes factor results showed that
      the most highly partitioned dataset is the preferred strategy among different
      partitioning schemes. The most striking phylogenetic findings were that the
      subfamily Danainae not Libytheinae was sister of the remaining brush-footed
      butterflies and that, within Limenitidini, the genus Athyma was clearly
      polyphyletic. None of the single-gene phylogenies recovered the highly supported
      topologies generated on the basis of the whole mitogenomic data. CONCLUSIONS:
      Thirty mitogenomes were assembled with 89% completeness from the contigs of
      pyrosequencing-derived reads. Entire mitogenomes or higher-quality sequences
      could be obtained by increasing pyrosequencing read coverage or by additional
      Sanger sequencing. Our mitogenomic phylogenies provide robust nodal support at a
      range of levels, demonstrating that mitogenomes are both accurate and efficient
      molecular markers for inferring butterfly phylogeny.

PMID- 24923778
TI  - Lie, truth, lie: the role of task switching in a deception context.
AB  - A cornerstone of the task switching literature is the finding that task
      performance is typically slower and more error-prone when the task switches than
      when it repeats. So far, deception research has largely ignored that such
      cognitive switch costs should also emerge when switching between truth telling
      and lying, and may affect the cognitive cost of lying as reflected in higher
      prefrontal brain activity and slower and less accurate responding compared to
      truth telling. To get a grasp on the relative size of the switch costs associated
      with lying and truth telling, the current study had participants perform a
      reaction time-based deception task, in which they alternated between lying and
      telling the truth to yes/no questions that were related to activities performed
      in the lab (Experiment 1) or neutral autobiographical facts (Experiment 2). In
      both experiments, the error and reaction time switch costs were found to be
      equally large for switching from truth telling to lying and from lying to truth
      telling. This symmetry in switch costs can be explained from the hypothesis that
      lying requires a first step of truth telling, and demonstrates that task
      switching does not contribute to the cognitive cost of lying when the
      repetition/switch ratio is balanced. Theoretical and methodological implications
      are considered. 

PMID- 24923779
TI  - The public health approach to reducing suicide: opportunities for curriculum
      development in psychiatry residency training programs.
AB  - The authors review the current status of suicide prevention curricula in
      psychiatry training programs, describe the public health approach to suicide
      prevention, discuss public health strategies for reducing suicides and the unique
      role played by psychiatrists with respect to suicide prevention, and offer public
      health-oriented suicide prevention curriculum guidelines for psychiatry
      residents. 

PMID- 24923780
TI  - Big pharma in residency training: losing more than a free lunch?

PMID- 24923781
TI  - Informal health care practices of residents: "curbside" consultation and self
      diagnosis and treatment.
AB  - OBJECTIVE: The authors explore the experiences of residents with respect to
      informal care related to personal health, including "curbside consultation," self
      diagnosis, and self-prescription-self-care practices that run counter to ethical
      guidelines in medicine. METHODS: Residents at one medical school completed a
      written survey regarding their personal health care practices, including their
      experiences in seeking or providing informal consultation, self-diagnosis, and
      self-prescribing. The authors obtained frequency data and analyzed responses via
      cross-tabulation. They used logistic regression models to assess the association
      of reported informal care practices and potential confounders, such as age,
      gender, and training program. RESULTS: One hundred and fifty-five residents
      volunteered (71 % response rate). Most respondents had sought health care
      formally (70 %), and more had sought informal care in the previous 12 months (80
      %). Of those who had pursued informal care, 90 % endorsed having requested a
      physical exam, a laboratory test, or a medication prescription from an attending,
      resident, or medical student. Respondents (28 %) commonly endorsed prescribing
      medication for themselves. Most respondents (90 %) reported being approached for
      informal care at least once in the previous year, including 84 % who were
      approached for prescriptions and 22 % who were approached by attending
      physicians. Main reasons endorsed for informal care seeking related to busy
      schedules and to cost and confidentiality advantages. Psychiatry residents
      reported using both formal and informal channels for personal health care, and 31
      % acknowledged prescribing medications for themselves. CONCLUSIONS: Informal care
      was a common practice among the residents in this study. Residents reported time
      constraints as the greatest influence on informal care seeking, rather than
      reasons found in previous studies related to cost and quality of care, protection
      of confidentiality, or prevention of embarrassment. The effects of informal care
      practices involving resident physicians warrant additional study.

PMID- 24923782
TI  - Analysis of the influence of cell heterogeneity on nanoparticle dose response.
AB  - Understanding the effect of variability in the interaction of individual cells
      with nanoparticles on the overall response of the cell population to a nanoagent
      is a fundamental challenge in bionanotechnology. Here, we show that the technique
      of time-resolved, high-throughput microscopy can be used in this endeavor. Mass
      measurement with single-cell resolution provides statistically robust assessments
      of cell heterogeneity, while the addition of a temporal element allows assessment
      of separate processes leading to deconvolution of the effects of particle supply
      and biological response. We provide a specific demonstration of the approach, in
      vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused
      by exposure to cationic nanoparticles. The results show that heterogeneity in
      cell area is the major source of variability with area-dependent nanoparticle
      capture rates determining the time of cell death and hence the form of the
      exposure-response characteristic. Moreover, due to the particulate nature of the
      nanoparticle suspension, there is a reduction in the particle concentration over
      the course of the experiment, eventually causing saturation in the level of
      measured biological outcome. A generalized mathematical description of the system
      is proposed, based on a simple model of particle depletion from a finite supply
      reservoir. This captures the essential aspects of the nanoparticle-cell
      interaction dynamics and accurately predicts the population exposure-response
      curves from individual cell heterogeneity distributions.

PMID- 24923784
TI  - Drosophila insulin-producing cells are differentially modulated by serotonin and
      octopamine receptors and affect social behavior.
AB  - A set of 14 insulin-producing cells (IPCs) in the Drosophila brain produces three
      insulin-like peptides (DILP2, 3 and 5). Activity in IPCs and release of DILPs is
      nutrient dependent and controlled by multiple factors such as fat body-derived
      proteins, neurotransmitters, and neuropeptides. Two monoamine receptors, the
      octopamine receptor OAMB and the serotonin receptor 5-HT1A, are expressed by the
      IPCs. These receptors may act antagonistically on adenylate cyclase. Here we
      investigate the action of the two receptors on activity in and output from the
      IPCs. Knockdown of OAMB by targeted RNAi led to elevated Dilp3 transcript levels
      in the brain, whereas 5-HT1A knockdown resulted in increases of Dilp2 and 5. OAMB
      RNAi in IPCs leads to extended survival of starved flies and increased food
      intake, whereas 5-HT1A-RNAi produces the opposite phenotypes. However, knockdown
      of either OAMB or 5-HT1A in IPCs both lead to increased resistance to oxidative
      stress. In assays of carbohydrate levels we found that 5-HT1A knockdown in IPCs
      resulted in elevated hemolymph glucose, body glycogen and body trehalose levels,
      while no effects were seen after OAMB knockdown. We also found that manipulations
      of the two receptors in IPCs affected male aggressive behavior in different ways
      and 5-HT1A-RNAi reduced courtship latency. Our observations suggest that
      activation of 5-HT1A and OAMB signaling in IPCs generates differential effects on
      Dilp transcription, fly physiology, metabolism and social interactions. However
      the findings do not support an antagonistic action of the two monoamines and
      their receptors in this particular system. 

PMID- 24923785
TI  - Mutation of essential Hsp90 co-chaperones SGT1 or CNS1 renders yeast
      hypersensitive to overexpression of other co-chaperones.
AB  - The essential molecular chaperone Hsp90 functions with over ten co-chaperones in
      Saccharomyces cerevisiae, but the in vivo roles of many of these co-chaperones
      are poorly understood. Two of these co-chaperones, Cdc37 and Sgt1, target
      specific types of clients to Hsp90 for folding. Other co-chaperones have general
      roles in supporting Hsp90 function, but the degree of overlapping or competing
      functions is unclear. None of the chaperones, when overexpressed, were able to
      rescue the lethality of an SGT1 disruption strain. However, overexpression of
      SBA1, PPT1, AHA1 or HCH1 caused varying levels of growth defects in an sgt1-K360E
      strain. Negative effects of CPR6 overexpression were similarly observed in cells
      expressing the temperature-sensitive mutation cns1-G90D. In all cases,
      alterations within co-chaperones designed to disrupt Hsp90 interaction relieved
      the negative growth defects. Sgt1-K360E and Cns1-G90D were previously shown to
      exhibit reduced Hsp90 interaction. Our results indicate that overexpression of
      other co-chaperones further disrupts the essential functions of Cns1 and Sgt1.
      However, the specificity of the negative effects indicates that only a subset of
      co-chaperones competes with Sgt1 or Cns1 for binding to Hsp90. This provides new
      evidence that co-chaperones selectively compete for binding to subpopulations of
      cellular Hsp90 and suggest that changes in the relative levels of co-chaperones
      may have dramatic effects on Hsp90 function.

PMID- 24923786
TI  - Bt-maize (MON810) and non-GM soybean meal in diets for Atlantic salmon (Salmo
      salar L.) juveniles--impact on survival, growth performance, development,
      digestive function, and transcriptional expression of intestinal immune and
      stress responses.
AB  - Responses in Atlantic salmon (Salmo salar L.) juveniles (fry) fed diets
      containing genetically modified maize (Bt-maize, MON810) expressing Cry1Ab
      protein from first-feeding were investigated during a 99-day feeding trial. Four
      experimental diets were made; each diet contained ~20% maize, either Bt-maize or
      its near-isogenic maternal line (non-GM maize). One pair was fishmeal-based while
      the other pair included standard (extracted) soybean meal (SBM; 16.7% inclusion
      level), with the intention of investigating responses to the maize varieties in
      healthy fish as well as in immunologically challenged fish with SBM-induced
      distal intestinal inflammation, respectively. Three replicate tanks of fry
      (0.17+/-0.01 g; initial mean weight +/- SEM) were fed one of the four diets and
      samples were taken on days 15, 36, 48 and 99. Survival, growth performance, whole
      body composition, digestive function, morphology of intestine, liver and
      skeleton, and mRNA expression of some immune and stress response parameters in
      the distal intestine were evaluated. After 99 days of feeding, survival was
      enhanced and the intended SBM-induced inflammatory response in the distal
      intestine of the two groups of SBM-fed fish was absent, indicating that the
      juvenile salmon were tolerant to SBM. Mortality, growth performance and body
      composition were similar in fish fed the two maize varieties. The Bt-maize fed
      fish, however, displayed minor but significantly decreased digestive enzyme
      activities of leucine aminopeptidase and maltase, as well as decreased
      concentration of gut bile salts, but significantly increased amylase activity at
      some sampling points. Histomorphological, radiographic and mRNA expression
      evaluations did not reveal any biologically relevant effects of Bt-maize in the
      gastrointestinal tract, liver or skeleton. The results suggest that the Cry1Ab
      protein or other compositional differences in GM Bt-maize may cause minor
      alterations in intestinal responses in juvenile salmon, but without affecting
      overall survival, growth performance, development or health. 

PMID- 24923788
TI  - Radiation dose reduction with dictionary learning based processing for head CT.
AB  - In CT, ionizing radiation exposure from the scan has attracted much concern from
      patients and doctors. This work is aimed at improving head CT images from low
      dose scans by using a fast Dictionary learning (DL) based post-processing. Both
      Low-dose CT (LDCT) and Standard-dose CT (SDCT) nonenhanced head images were
      acquired in head examination from a multi-detector row Siemens Somatom Sensation
      16 CT scanner. One hundred patients were involved in the experiments. Two groups
      of LDCT images were acquired with 50 % (LDCT50 %) and 25 % (LDCT25 %) tube
      current setting in SDCT. To give quantitative evaluation, Signal to noise ratio
      (SNR) and Contrast to noise ratio (CNR) were computed from the Hounsfield unit
      (HU) measurements of GM, WM and CSF tissues. A blinded qualitative analysis was
      also performed to assess the processed LDCT datasets. Fifty and seventy five
      percent dose reductions are obtained for the two LDCT groups (LDCT50 %, 1.15 +/-
      0.1 mSv; LDCT25 %, 0.58 +/- 0.1 mSv; SDCT, 2.32 +/- 0.1 mSv; P < 0.001).
      Significant SNR increase over the original LDCT images is observed in the
      processed LDCT images for all the GM, WM and CSF tissues. Significant GM-WM CNR
      enhancement is noted in the DL processed LDCT images. Higher SNR and CNR than the
      reference SDCT images can even be achieved in the processed LDCT50 % and LDCT25 %
      images. Blinded qualitative review validates the perceptual improvements brought
      by the proposed approach. Compared to the original LDCT images, the application
      of DL processing in head CT is associated with a significant improvement of image
      quality. 

PMID- 24923787
TI  - Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA.
AB  - The endoplasmic reticulum (ER) and mitochondria accumulate Ca(2+) within their
      lumens to regulate numerous cell functions. However, determining the dynamics of
      intraorganellar Ca(2+) has proven to be difficult. Here we describe a family of
      genetically encoded Ca(2+) indicators, named calcium-measuring organelle
      entrapped protein indicators (CEPIA), which can be utilized for intraorganellar
      Ca(2+) imaging. CEPIA, which emit green, red or blue/green fluorescence, are
      engineered to bind Ca(2+) at intraorganellar Ca(2+) concentrations. They can be
      targeted to different organelles and may be used alongside other fluorescent
      molecular markers, expanding the range of cell functions that can be
      simultaneously analysed. The spatiotemporal resolution of CEPIA makes it possible
      to resolve Ca(2+) import into individual mitochondria while simultaneously
      measuring ER and cytosolic Ca(2+). We have used these imaging capabilities to
      reveal differential Ca(2+) handling in individual mitochondria. CEPIA imaging is
      a useful new tool to further the understanding of organellar functions. 

PMID- 24923789
TI  - New in situ trapping metalations of functionalized arenes and heteroarenes with
      TMPLi in the presence of ZnCl2 and other metal salts.
AB  - The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate
      with a metal salt such as MgCl2, ZnCl2, or CuCN at -78  degrees C first leads to
      lithiation of the arene followed by transmetalation with the metal salt to afford
      functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping
      method allows an expedited metalation (-78  degrees C, 5 min) of a range of
      sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the
      preparation of kinetic regioisomers of functionalized aromatic compounds or
      heterocycles not otherwise available by standard metalating agents, such as
      TMPMgCl?LiCl or TMPZnCl?LiCl.

PMID- 24923790
TI  - Differences in regional adiposity, bone mineral density, and physical exercise
      participation based on exercise self-efficacy among senior adults.
AB  - AIM: The impact of exercise self-efficacy levels (ESE) on exercise participation,
      levels of body fat (BF), and bone mineral density (BMD) are unclear in senior
      aged adults. The purpose of this study was to investigate effects of ESE on
      exercise participation, regional distribution of BF, and BMD among seniors.
      METHODS: Senior adults (N.=76; 36 males, 40 females) were separated into tertiles
      (T1, age=60.4+/-1.4; T2, age=61.3+/-1.4; T3, age=60.4+/-1.5) based on self
      reported levels of ESE. BMD and regional BF were measured using dual-energy x-ray
      absorptiometry and exercise participation levels were measured using the Rapid
      Physical-Activity Questionnaire. RESULTS: MANOVA revealed a significant Wilks
      Lambda (p < 0.001) and univariate analysis was completed for exercise
      participation levels, android BF, gynoid BF, and spinal BMD. ANOVA revealed T3
      was significantly lower for android BF (p=0.002) than T1 and T2 (30% and 26%,
      respectively) while gynoid BF was significantly lower (p=0.012) for T3 (24%)
      compared to T1. When evaluating exercise participation levels, T3 was
      significantly higher (p < 0.001) than T1 or T2. Spinal BMD was significantly
      higher (p=0.030) between T2 (10%) and T1. CONCLUSION: ESE is an important factor
      in senior adults ability to maintain longitudinal health.

PMID- 24923792
TI  - Exploratory study of the effect of lifestyle counselling on bone mineral density
      and body composition in users of the contraceptive depot-medroxyprogesterone
      acetate.
AB  - OBJECTIVES: To compare variations in bone mineral density (BMD) and body
      composition (BC) in depot-medroxyprogesterone acetate (DMPA) users and nonusers
      after providing counselling on healthy lifestyle habits. METHODS: An exploratory
      study in which women aged 18 to 40 years participated: 29 new DMPA users and 25
      new non-hormonal contraceptive users. All participants were advised on healthy
      lifestyle habits: sun exposure, walking and calcium intake. BMD and BC were
      assessed at baseline and 12 months later. Statistical analysis included the Mann
      Whitney test or Student's t-test followed by multiple linear regression analysis.
      RESULTS: Compared to the controls, DMPA users had lower BMD at vertebrae L1 and
      L4 after 12 months of use. They also had a mean increase of 2 kg in total fat
      mass and an increase of 2.2% in body fat compared to the non-hormonal
      contraceptive users. BMD loss at L1 was less pronounced in DMPA users with a
      calcium intake >= 1 g/day compared to DMPA users with a lower calcium intake.
      CONCLUSIONS: DMPA use was apparently associated with lower BMD and an increase in
      fat mass at 12 months of use. Calcium intake >= 1 g/day attenuates BMD loss in
      DMPA users. Counselling on healthy lifestyle habits failed to achieve its aims.

PMID- 24923794
TI  - Mean platelet volume and platelet distribution width can be related to bone
      mineralization.
AB  - Platelets functions are related to bone resorption and formation. The present
      study aimed at studying the association between platelet function and bone
      mineralization. We showed that mean platelet volume (MPV) and platelet
      distribution width (PDW) levels in osteoporosis patients increased. The study
      also showed that PDW and age independently associated with bone mineralization.
      INTRODUCTION: MPV and PDW are widely used for assessing platelet function.
      Recently, authors argued that platelet function has an important role in bone
      mineralization. However, only one study has investigated the relationship between
      MPV and osteoporosis. We aimed to study the levels of MPV and PDW in
      postmenopausal osteoporosis. METHODS: We investigated 320 bone mineral density
      (BMD) measurements between the years 2012 and 2013 retrospectively in our clinic.
      Eighty patients whom chronic diseases are absent and all laboratory findings are
      complete enrolled in this study. Patients were divided in three groups as an
      osteoporosis, osteopenia, and normal BMD group. MPV and PDW levels were
      investigated in these groups. We performed correlation test and linear regression
      analysis to determine whether there is a relationship between platelet function
      markers and BMD measurements. RESULTS: Eighty patients were divided as an
      osteoporosis, osteopenia, and normal BMD group. MPV levels and PDW levels in the
      osteoporosis group were lower than the normal BMD group. PDW was positively
      correlated with femur total T (FTT) score and lumbar 1-4T (L1-4T) scores. Linear
      regression analysis showed that age and PDW were independently related to FTT and
      LTT scores. CONCLUSION: Platelet functions are related to the bone
      mineralization. PDW and MPV have a significant role in the development of
      postmenopausal osteoporosis.

PMID- 24923793
TI  - Clustering and correlates of multiple health behaviours in 9-10 year old
      children.
AB  - BACKGROUND: Sleep, physical activity, screen time and dietary behaviours
      influence health during childhood, but few studies have looked at all of these
      behaviours simultaneously and previous research has relied predominantly on self-
      or proxy-reports of physical activity and food frequency questionnaires for the
      assessment of diet. PURPOSE: To assess the prevalence and clustering of health
      behaviours and examine the socio-demographic characteristics of children that
      fail to meet multiple health behaviour guidelines. METHODS: Data are from the
      Sport, Physical activity and Eating behaviour: Environmental Determinants in
      Young people (SPEEDY) study. Participants (n = 1472, 42.9% male) were
      dichotomized based on whether or not they met public health guidelines for
      accelerometer-assessed physical activity, diet-diary assessed fruit/vegetable
      intake and fat/non-milk extrinsic sugar (NMES) intake, and self-reported screen
      time and sleep duration. Behavioural clustering was assessed using an observed
      over expected ratio (O/E). Socio-demographic characteristics of participants that
      failed to meet multiple health behaviour guidelines were examined using ordinal
      logistic regression. Data were analysed in 2013. RESULTS: 83.3% of children
      failed to meet guidelines for two or more health behaviours. The O/E ratio for
      two behavioural combinations significantly exceeded 1, both of which featured
      high screen time, insufficient fruit/vegetable consumption and excessive fat/NMES
      intake. Children who were older (Proportional odds ratio (95% confidence
      interval): 1.69 (1.21,2.37)) and those that attended a school with a physical
      activity or diet-related policy (1.28 (1.01,1.62)) were more likely to have a
      poor health behaviour profile. Girls (0.80 (0.64,0.99)), participants with
      siblings (0.76 (0.61,0.94)) and those with more highly educated parents (0.73
      (0.56,0.94)) were less likely to have a poor health behaviour profile.
      CONCLUSIONS: A substantial proportion of children failed to meet guidelines for
      multiple health behaviours and there was evidence of clustering of screen viewing
      and unhealthy dietary behaviours. Sub-groups at greatest risk may be targeted for
      intervention.

PMID- 24923795
TI  - Validation of Waffle procedure for constrictive pericarditis with epicardial
      thickening.
AB  - OBJECTIVE: Waffle procedure, a small grid-like incision of epicardium, is a
      surgical technique for constrictive pericarditis with epicardial thickening. Yet
      evidences to endorse this approach for improved outcomes are lacking. The aim of
      this study is to elucidate better surgical treatment strategy for constrictive
      pericarditis with epicardial thickening. METHODS: Twenty-five patients (mean 64.1
      years) who underwent pericardiectomy for constrictive pericarditis between
      January 1992 and July 2012 were included in this study and were classified into
      two groups according to the procedure they received; single total pericardiectomy
      (Group A, n = 17) and total pericardiectomy with the Waffle procedure (Group B, n
      = 8). Early and mid-term outcomes were analyzed for each group. RESULTS: No major
      postoperative complications or all-cause deaths at 30 days were observed in each
      group. Upon discharge, postoperative echocardiography showed statistically
      significant increase of left ventricular end-diastolic volume (from 76.6 +/- 30.3
      to 91.0 +/- 27.3 ml; p < 0.02) and systolic volume (from 44.4 +/- 19.1 to 54.5 +/
      17.3 ml; p < 0.05) in Group B than those in Group A. The 5-year cardiac event
      free rate was similar between groups [83.6 +/- 10.8 % for group A and 83.3 +/-
      15.2 % for group B (p = NS)] as well as the mean value of NYHA classification for
      each at the mid-term periods (1.5 for Group A and 1.3 for Group B). CONCLUSION:
      Waffle procedure improved echocardiographic elements of diastolic function of
      patients with epicardial thickening more than did total pericardiectomy without
      additional compromises.

PMID- 24923796
TI  - Decline of fiber tract integrity over the adult age range: a diffusion spectrum
      imaging study.
AB  - PURPOSE: We applied a novel diffusion spectrum imaging (DSI) acquisition to
      determine associations between aging and subcortical fiber tract integrity.
      MATERIALS AND METHODS: We studied 35 cognitively healthy subjects (17 women),
      spanning the adult age range between 23 and 77 years, using anatomical MRI and a
      novel DSI acquisition scheme at 3 Tesla. The study was approved by the local
      institutional review board. DSI data were analyzed using tractography and
      complementary voxel-based analysis of generalized fractional anisotropy (GFA)
      maps. We determined the effects of age on generalized fractional anisotropy in
      selected fiber tracts as well as in a whole brain voxel-based analysis. For
      comparison, we studied the effects of age on regional gray and white matter
      volumes. RESULTS: We found a significant reduction in anterior corpus callosum
      fiber tract integrity with age (P < 0.001), as well as significant GFA reduction
      throughout the subcortical white matter (P < 0.05, false discovery rate [FDR]
      corrected). GFA decline was accompanied by significant gray matter atrophy in
      frontal and temporal association cortex (P < 0.05, FDR corrected). CONCLUSION:
      Our data suggest that normal aging leads to a regionally specific decline in
      fiber tract integrity. DSI may become a useful biomarker in healthy and
      pathological aging.

PMID- 24923797
TI  - Robust detection of tyrosine phosphatase activity by coupling chymotrypsin
      assisted selective peptide cleavage and a graphene oxide-based fluorescent
      platform.
AB  - A versatile graphene oxide (GO)-based fluorescent assay is developed for the
      detection of protein tyrosine phosphatase activity by coupling with a
      chymotrypsin-assisted selective peptide cleavage reaction. 

PMID- 24923799
TI  - What information is used by rats to update choices in the radial-arm maze?
AB  - This study examined the information processed by rats in the radial maze. In
      Experiment 1, performance in the standard straight-arm radial maze was compared
      with performance in a angle-arm maze which required a right turn at the end of
      each radial arm. The results showed that the performance of rats initially
      trained in the angle-arm maze was much more affected when later tested on the
      straight-arm maze than was the performance of rats initially trained on the
      straight-arm maze and then moved to the angle-arm maze. In Experiment 2, two
      groups of rats were trained in the angle-arm maze and then subjected to two
      transfer tests during which the location and/or direction of the correct goal
      arms was manipulated. Both transfer tests produced an increase in errors, but the
      increase was much more pronounced in rats required to learn a new set of baited
      locations than in rats tested on the same set of baited locations and required to
      use new initial travel directions. Together, these experiments demonstrate that
      rats make complementary use of information about both initial travel direction
      and goal location. 

PMID- 24923798
TI  - The effects of protein malnutrition and cortisol treatment on motor activity of
      rats.
AB  - Virgin female Wistar rats were randomly assigned to one of three isocaloric diets
      (20, 11 and 6.7% protein content). From a week prior to mating and during
      gestation and suckling periods they were fed ad lib. At the beginning of
      gestation period each dietary group was subdivided into two groups according to
      the treatment with a daily injection of either hydrocortisone acetate solution or
      saline solution they were to receive until delivery. After weaning, only the male
      pups were selected and fed ad lib with the same diet as their mothers. They were
      weighed and evaluated in an open field test every 10 days for 70 days. The body
      weight of the animals diminished as protein content in diet decreased. The 6.7%
      group was hyperactive and less emotional than the other dietary groups. The 11%
      group showed more vertical activity than the 20 and 6.7% groups. Cortisol
      administration during gestation decreased motor activity in the 20% group, but
      had no effect on the two malnourished groups. 

PMID- 24923800
TI  - Forebrain-mediated control of visually guided prey-catching in toads:
      investigation of striato-pretectal connections with intracellular
      recording/labeling methods.
AB  - Studies in anurans have shown that ablation of the whole telencephalon (or the
      caudal striatum) abolishes visual prey-catching behavior, whereas an additional
      lesion to the pretectum leads to hyperexcited, "disinhibited" prey-catching. This
      suggests a disinhibitory gating/arousal function mediated by two inhibitory
      projections: telencephalon to pretectum and pretectum to tectum. Since the latter
      projection has been physiologically investigated already in great detail, the
      present paper focuses on the former projection. Intracellular recordings from the
      pretectal region in response to electrical stimulation of the ipsilateralcaudal
      ventral striatum or the ipsilateral lateral forebrain bundle revealed cells that
      display pure inhibitory postsynaptic potentials with short latencies of 2-3 ms,
      indicative for monosynaptic striato-pretectal connection. But it must be
      emphasized that a relatively large number of pretectal neurons of this sample
      showed sequential excitatory/inhibitory postsynaptic potentials. The latter data
      are not in conflict, with the hypothesis, rather they open new perspectives for
      further investigations. 

PMID- 24923801
TI  - The effects of social deprivation on levels of social play in the laboratory rat
      Rattus norvegicus.
AB  - Previous studies on a variety of species suggest the existence of a 'rebound'
      effect in social play: young animals may show heightened levels of play,
      following temporary deprivation of opportunity for social interaction. The
      present experiment investigated this phenomenon in greater detail, by measuring
      the effect of different types of social deprivation on levels of social play in
      prepubescent laboratory rats Rattus norvegicus. In one deprivation condition,
      subjects were denied whole-body contact, but not other forms of social
      interaction; in another condition, subjects experienced more extensive isolation.
      Both kinds of deprivation produced equally large post-deprivation increases in
      social play, suggesting that the important factor in producing the rebound effect
      is the absence of opportunity for whole-body contact - the predominant component
      of "rough and tumble" social play. 

PMID- 24923802
TI  - Ethoexperimental analysis of the impact of chlordiazepoxide (CDP) on social
      interactions in three strains of mice.
AB  - Categories of male C57BL/10, BALB/c and Swiss mice were injected s.c. with saline
      or 2.5, 5 or 10 mg/kg of CDP in saline 15 min prior to encounters with
      peripherally anosmic Swiss male 'standard opponents'. The 10-min encounters were
      videotaped and subsequently analysed using a microprocessor for the times
      allocated to 11 broad ethological categories of behaviour. The animal's genotype
      had a profound effect on its response to CDP, effects being evident on attack,
      threat, avoidance-flee, defensive-submissive behaviour, social investigation, non
      social investigation, digging and exploration-from-a-distance. Only body care and
      immobility showed no clear strain effect. A dose-effect of CDP was only evident
      on defense-submission - indeed the drug progressively increased the incidence of
      this behaviour in all strains. 

PMID- 24923803
TI  - Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and
      Ap3m2 expression using integrative functional genomics and precision genetics.
AB  - Extensive genetic and genomic studies of the relationship between alcohol
      drinking preference and withdrawal severity have been performed using animal
      models. Data from multiple such publications and public data resources have been
      incorporated in the GeneWeaver database with >60,000 gene sets including 285
      alcohol withdrawal and preference-related gene sets. Among these are evidence for
      positional candidates regulating these behaviors in overlapping quantitative
      trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration
      of functional genomics experimental results revealed a single QTL positional
      candidate gene in one of the loci common to both preference and withdrawal.
      Functional validation studies in Ap3m2 knockout mice confirmed these
      relationships. Genetic validation involves confirming the existence of
      segregating polymorphisms that could account for the phenotypic effect. By
      exploiting recent advances in mouse genotyping, sequence, epigenetics, and
      phylogeny resources, we confirmed that Ap3m2 resides in an appropriately
      segregating genomic region. We have demonstrated genetic and alcohol-induced
      regulation of Ap3m2 expression. Although sequence analysis revealed no
      polymorphisms in the Ap3m2-coding region that could account for all phenotypic
      differences, there are several upstream SNPs that could. We have identified one
      of these to be an H3K4me3 site that exhibits strain differences in methylation.
      Thus, by making cross-species functional genomics readily computable we
      identified a common QTL candidate for two related bio-behavioral processes via
      functional evidence and demonstrate sufficiency of the genetic locus as a source
      of variation underlying two traits. 

PMID- 24923804
TI  - Fertility and polarized cell growth depends on eIF5A for translation of
      polyproline-rich formins in Saccharomyces cerevisiae.
AB  - eIF5A is an essential and evolutionary conserved translation elongation factor,
      which has recently been proposed to be required for the translation of proteins
      with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its
      activation by hypusination, a modification that requires spermidine, an essential
      factor for mammalian fertility that also promotes yeast mating. We show that in
      response to pheromone, hypusinated eIF5A is required for shmoo formation,
      localization of polarisome components, induction of cell fusion proteins, and
      actin assembly in yeast. We also show that eIF5A is required for the translation
      of Bni1, a proline-rich formin involved in polarized growth during shmoo
      formation. Our data indicate that translation of the polyproline motifs in Bni1
      is eIF5A dependent and this translation dependency is lost upon deletion of the
      polyprolines. Moreover, an exogenous increase in Bni1 protein levels partially
      restores the defect in shmoo formation seen in eIF5A mutants. Overall, our
      results identify eIF5A as a novel and essential regulator of yeast mating through
      formin translation. Since eIF5A and polyproline formins are conserved across
      species, our results also suggest that eIF5A-dependent translation of formins
      could regulate polarized growth in such processes as fertility and cancer in
      higher eukaryotes. 

PMID- 24923805
TI  - Placing epidemiological results in the context of multiplicity and typical
      correlations of exposures.
AB  - Epidemiological studies evaluate multiple exposures, but the extent of
      multiplicity often remains non-transparent when results are reported. There is
      extensive debate in the literature on whether multiplicity should be adjusted for
      in the design, analysis, and reporting of most epidemiological studies, and, if
      so, how this should be done. The challenges become more acute in an era where the
      number of exposures that can be studied (the exposome) can be very large. Here,
      we argue that it can be very insightful to visualize and describe the extent of
      multiplicity by reporting the number of effective exposures for each category of
      exposures being assessed, and to describe the distribution of correlation between
      exposures and/or between exposures and outcomes in epidemiological datasets. The
      results of new proposed associations can be placed in the context of this
      background information. An association can be assigned to a percentile of
      magnitude of effect based on the distribution of effects seen in the field. We
      offer an example of how such information can be routinely presented in an
      epidemiological study/dataset using data on 530 exposure and demographic
      variables classified in 32 categories in the National Health and Nutrition
      Examination Survey (NHANES). Effects that survive multiplicity considerations and
      that are large may be prioritized for further scrutiny.

PMID- 24923806
TI  - Primary health-care costs associated with special health care needs up to age 7
      years: Australian population-based study.
AB  - AIM: We studied infants and children with and without special health care needs
      (SHCN) during the first 8 years of life to compare the (i) types and costs to the
      government's Medicare system of non-hospital health-care services and
      prescription medication in each year and (ii) cumulative costs according to
      persistence of SHCN. METHODS: Data from the first two biennial waves of the
      nationally representative Longitudinal Study of Australian Children, comprising
      two independent cohorts recruited in 2004, at ages 0-1 (n = 5107) and 4-5 (n =
      4983) years. Exposure condition: parent-reported Children with Special Health
      Care Needs Screener at both waves, spanning ages 0-7 years. OUTCOME MEASURE:
      Federal Government Medicare expenditure, via data linkage to the Medicare
      database, on non-hospital health-care attendances and prescriptions from birth to
      8 years. RESULTS: At both waves and in both cohorts, >92% of children had
      complete SHCN and Medicare data. The proportion of children with SHCN increased
      from 6.1% at age 0-1 years to 15.0% at age 6-7 years. Their additional Medicare
      costs ranged from $491 per child at 6-7 years to $1202 at 0-1 year. This equates
      to an additional $161.8 million annual cost or 0.8% of federal funding for non
      hospital-based health care. In both cohorts, costs were highest for children with
      persistent SHCNs. CONCLUSIONS: SHCNs incur substantial non-hospital costs to
      Medicare, and no doubt other sources of care, from early childhood. This suggests
      that economic evaluations of early prevention and intervention services for SHCNs
      should consider impacts on not only the child and family but also the health-care
      system.

PMID- 24923807
TI  - Zwitterionic red fluorescent polymeric nanoparticles for cell imaging.
AB  - Phospholipid monomer and aggregation-induced emission (AIE) dye-based dimers are
      incorporated via reversible addition-fragmentation transfer polymerization to
      afford cross-linked zwitterionic fluorescent copolymers. Such copolymers are
      prone to self-assembly into fluorescent polymeric nanoparticles (FPNs) in
      physiological solution due to their amphiphilic nature. Characterization of these
      red FPNs by Fourier-transform infrared spectroscopy and X-ray photoelectron
      spectroscopy indicates the successful preparation of these zwitterionic
      copolymers. UV-visible absorption spectroscopy, fluorescence spectroscopy,
      transmission electron microscopy, and dynamic light scattering are performed to
      demonstrate the bright red fluorescence of the FPNs and their stable
      dispersibilities, even below the critical micelle concentration in physiological
      solution. Finally, studies of the biocompatibility and cell uptake behavior of
      the FPNs are conducted and show excellent biocompatibility for cell imaging
      application. 

PMID- 24923809
TI  - Benefits of trastuzumab outweigh its harms, says Cochrane review.

PMID- 24923808
TI  - No evidence of benefit from antibiotic lock therapy in pediatric oncology
      patients with central line-related bloodstream infection: results of a
      retrospective matched cohort study and review of the literature.
AB  - BACKGROUND: Long-term central venous catheters (CVCs) are essential to modern
      pediatric oncology practice, but central line-related bloodstream infection
      (CRBSI) is a frequent and important complication. CVC salvage is often attempted
      but treatment failure is common due to persistent infection, delayed catheter
      removal, or subsequent relapse of infection, which can be associated with
      significant morbidity and cost. Adjunctive antibiotic lock therapy (ALT) has been
      proposed to reduce the risk of treatment failure, but insufficient data are
      available to confirm efficacy of this intervention. PROCEDURE: We undertook a
      retrospective matched cohort study of ALT use for treatment of CRBSI in pediatric
      hematology/oncology patients at St. Jude Children's Research Hospital between
      2006 and 2012. RESULTS: Thirty-eight eligible episodes of CRBSI treated with
      adjunctive ALT were identified and compared to 73 episodes treated with standard
      therapy (ST) alone, matched by catheter-type and organism. Overall, treatment
      failure was similar between ALT and ST groups (50.0 vs. 38.4%; P = 0.24), but the
      timing was different; in the ALT cohort, immediate CVC removal was less common
      (0.0 vs. 12.3%; P = 0.03) but delayed removal (4-13 days) and relapse of
      infection was more common (50.0 vs. 24.7%; P = 0.01). CONCLUSIONS: This
      retrospective study was unable to identify any benefit of adjunctive ALT in
      pediatric oncology patients with CRBSI. The available evidence does not support
      routine ALT use, and well-conducted prospective studies are needed.

PMID- 24923810
TI  - A case of anaphylactic shock induced by FX60 polysulfone hemodialyzer but not F6
      HPS polysulfone hemodialyzer.
AB  - A 75-year-old woman was admitted for dyspnea and fever. She underwent emergent
      dialysis smoothly under F6-HPS polysulfone hemodialyzer. With two subsequent
      hemodialysis sessions, severe anaphylactic reaction with cardiopulmonary
      resuscitation occurred under FX60 polysulfone dialyzer. Further dialysis sessions
      by F6-HPS polysulfone dialyzer were uneventful. This rare case demonstrated that
      dialyzer reaction may be markedly different even with the same material and the
      same manufacturer. 

PMID- 24923812
TI  - Status of intertidal infaunal communities following the Exxon Valdez oil spill in
      Prince William Sound, Alaska.
AB  - Intertidal infaunal communities were sampled in Prince William Sound, Alaska from
      1990-2000 to evaluate impacts and recovery from the Exxon Valdez oil spill.
      Initial findings suggested that the spill and cleanup depressed abundances of all
      taxonomic groups. By 1992, abundances of major taxonomic categories at disturbed
      sites had either converged or paralleled populations at Unoiled sites. Abundances
      of littleneck clams, Leukoma (Protothaca) staminea, slowly increased at Treated
      sites and converged with Unoiled sites by 2000. Infaunal population differences
      positively correlated with fine-grained sediments at Treated sites. We believe
      that sediment fines removal during cleanup, and subsequent slow natural
      replenishment, impeded the return of the environment to pre-spill conditions.
      This suggests physical recovery of spill-affected beaches is an important
      precursor to biological recovery. 

PMID- 24923811
TI  - Adherence to oral diabetes medications and glycemic control during and following
      breast cancer treatment.
AB  - OBJECTIVES: We evaluated changes in oral diabetes mellitus medication adherence
      and persistence, as well as glycemic control for the year prior to breast cancer
      (BC) diagnosis (Year -1), during BC treatment, and in subsequent years. METHODS:
      Cohort study of 4216 women diagnosed with incident early stage (I and II)
      invasive BC from 1990-2008, enrolled in Group Health Cooperative. Adherence was
      measured in prevalent users at baseline (N = 509), during treatment, and 1-3
      years post-diagnosis using medication possession ratio (MPR), % adherent (MPR
      >=0.80) and discontinuation rates. Laboratory data on glycosylated hemoglobin
      (HbA1c ) was obtained for the corresponding periods. RESULTS: Compared with Year 
      1, mean MPR for metformin/sulfonylureas (0.86 vs 0.49, p < 0.001) and % adherent
      (75.3% vs 24.6%, p < 0.001) declined during BC treatment. MPR and % adherent rose
      slightly during Years 1-3 post-diagnosis but never returned to baseline.
      Discontinuation rates increased from treatment to Year +1 (59.3% vs 75.6%, p <
      0.001) and remained elevated during subsequent observation periods. Compared with
      baseline, increased HbA1c (7.0% vs 7.4%, p = 0.001) and % women with high HbA1c
      >7.0% (34.9% vs 51.1%, p < 0.001) coincided with decreased adherence. CONCLUSION:
      Diabetes mellitus medication adherence declined following BC diagnosis, whereas
      discontinuation rates were relatively stable but poor overall. The proportion of
      adherent users increased only marginally following treatment, whereas the
      proportion of women meeting goals for HbA1c decreased considerably. These data
      support the hypothesis that adherence and subsequent glycemic control are
      sensitive to BC diagnosis and treatment. Confirmatory studies in other settings,
      on reasons for reduced adherence post-cancer diagnosis, and on subsequent
      indicators of glycemic control are warranted.

PMID- 24923813
TI  - Development and application of an oil spill model with wave-current interactions
      in coastal areas.
AB  - The present paper focuses on developing a numerical oil spill model that
      incorporates the full three-dimensional wave-current interactions for a better
      representation of the spilled oil transport mechanics in complicated coastal
      environments. The incorporation of surface wave effects is not only imposing a
      traditional drag coefficient formulation at the free surface, but also the 3D
      momentum equations are adjusted to include the impact of the vertically dependent
      radiation stresses on the currents. Based on the current data from SELFE and wave
      data from SWAN, the oil spill model utilizes oil particle method to predict the
      trajectory of individual droplets and the oil concentration. Compared with the
      observations in Dalian New Port oil spill event, the developed model taking into
      account wave-current coupling administers to giving better conformity than the
      one without. The comparisons demonstrates that 3D radiation stress impacts the
      spill dynamics drastically near the sea surface and along the coastline, while
      having less impact in deeper water. 

PMID- 24923814
TI  - delta(15)N variation in Ulva lactuca as a proxy for anthropogenic nitrogen inputs
      in coastal areas of Gulf of Gaeta (Mediterranean Sea).
AB  - We tested the capacity of Ulva lactuca to mark N sources across large marine
      areas by measuring variation in its delta(15)N at several sites in the Gulf of
      Gaeta. Comparisons were made with the macroalga Cystoseira amentacea. Variation
      of delta(15)N values was assessed also in the coastal waters off the Circeo
      Natural Park, where U. lactuca and C. amentacea were harvested, as these waters
      are barely influenced by human activities and were used as reference site. A
      small fragment from each frond was preserved before deployment in order to
      characterize the initial isotopic values. After 48 h of submersion, U. lactuca
      was more responsive than C. amentacea to environmental variation and delta(15)N
      enrichment in the Gulf of Gaeta was observed. The spatial distribution of
      delta(15)N enrichment indicated that different macro-areas in the Gulf were
      affected by N inputs from different origins. Comparison of the delta(15)N values
      of fragments taken from the same transplanted frond avoided bias arising from
      natural isotopic variability.

PMID- 24923815
TI  - Clinical importance of risk variants in the dihydropyrimidine dehydrogenase gene
      for the prediction of early-onset fluoropyrimidine toxicity.
AB  - We investigated the clinical relevance of dihydropyrimidine dehydrogenase gene
      (DPYD) variants to predict severe early-onset fluoropyrimidine (FP) toxicity, in
      particular of a recently discovered haplotype hapB3 and a linked deep intronic
      splice site mutation c.1129-5923C>G. Selected regions of DPYD were sequenced in
      prospectively collected germline DNA of 500 patients receiving FP-based
      chemotherapy. Associations of DPYD variants and haplotypes with hematologic,
      gastrointestinal, infectious, and dermatologic toxicity in therapy cycles 1-2 and
      resulting FP-dose interventions (dose reduction, therapy delay or cessation) were
      analyzed accounting for clinical and demographic covariates. Fifteen additional
      cases with toxicity-related therapy delay or cessation were retrospectively
      examined for risk variants. The association of c.1129-5923C>G/hapB3 (4.6% carrier
      frequency) with severe toxicity was replicated in an independent prospective
      cohort. Overall, c.1129-5923G/hapB3 carriers showed a relative risk of 3.74 (RR,
      95% CI = 2.30-6.09, p = 2 * 10(-5)) for severe toxicity (grades 3-5). Of 31 risk
      variant carriers (c.1129-5923C>G/hapB3, c.1679T>G, c.1905+1G>A or c.2846A>T), 11
      (all with c.1129-5923C>G/hapB3) experienced severe toxicity (15% of 72 cases, RR
      = 2.73, 95% CI = 1.61-4.63, p = 5 * 10(-6)), and 16 carriers (55%) required FP
      dose interventions. Seven of the 15 (47%) retrospective cases carried a risk
      variant. The c.1129-5923C>G/hapB3 variant is a major contributor to severe early
      onset FP toxicity in Caucasian patients. This variant may substantially improve
      the identification of patients at risk of FP toxicity compared to established
      DPYD risk variants (c.1905+1G>A, c.1679T>G and c.2846A>T). Pre-therapeutic DPYD
      testing may prevent 20-30% of life-threatening or lethal episodes of FP toxicity
      in Caucasian patients.

PMID- 24923816
TI  - Comparison of block and event-related experimental designs in diffusion-weighted
      functional MRI.
AB  - PURPOSE: To compare diffusion-weighted functional magnetic resonance imaging
      (DfMRI), a novel alternative to the blood oxygenation level-dependent (BOLD)
      contrast, in a functional MRI experiment. MATERIALS AND METHODS: Nine
      participants viewed contrast reversing (7.5 Hz) black-and-white checkerboard
      stimuli using block and event-related paradigms. DfMRI (b = 1800 mm/s(2)) and
      BOLD sequences were acquired. Four parameters describing the observed signal were
      assessed: percent signal change, spatial extent of the activation, the Euclidean
      distance between peak voxel locations, and the time-to-peak of the best fitting
      impulse response for different paradigms and sequences. RESULTS: The BOLD
      conditions showed a higher percent signal change relative to DfMRI; however,
      event-related DfMRI showed the strongest group activation (t = 21.23, P <
      0.0005). Activation was more diffuse and spatially closer to the BOLD response
      for DfMRI when the block design was used. DfMRIevent showed the shortest TTP (4.4
      +/- 0.88 sec). CONCLUSION: The hemodynamic contribution to DfMRI may increase
      with the use of block designs.

PMID- 24923817
TI  - Ermod: fast and versatile computation software for solvation free energy with
      approximate theory of solutions.
AB  - ERmod is a software package to efficiently and approximately compute the
      solvation free energy using the method of energy representation. Molecular
      simulation is to be conducted at two condensed-phase systems of the solution of
      interest and the reference solvent with test-particle insertion of the solute.
      The subprogram ermod in ERmod then provides a set of energy distribution
      functions from the simulation trajectories, and another subprogram slvfe
      determines the solvation free energy from the distribution functions through an
      approximate functional. This article describes the design and implementation of
      ERmod, and illustrates its performance in solvent water for two organic solutes
      and two protein solutes. Actually, the free-energy computation with ERmod is not
      restricted to the solvation in homogeneous medium such as fluid and polymer and
      can treat the binding into weakly ordered system with nano-inhomogeneity such as
      micelle and lipid membrane. ERmod is available on web at
      http://sourceforge.net/projects/ermod.

PMID- 24923818
TI  - ParaPep: a web resource for experimentally validated antiparasitic peptide
      sequences and their structures.
AB  - ParaPep is a repository of antiparasitic peptides, which provides comprehensive
      information related to experimentally validated antiparasitic peptide sequences
      and their structures. The data were collected and compiled from published
      research papers, patents and from various databases. The current release of
      ParaPep holds 863 entries among which 519 are unique peptides. In addition to
      peptides having natural amino acids, ParaPep also consists of peptides having d
      amino acids and chemically modified residues. In ParaPep, most of the peptides
      have been evaluated for growth inhibition of various species of Plasmodium,
      Leishmania and Trypanosoma. We have provided comprehensive information about
      these peptides that include peptide sequence, chemical modifications,
      stereochemistry, antiparasitic activity, origin, nature of peptide, assay types,
      type of parasite, mode of action and hemolytic activity. Structures of peptides
      consisting of natural, as well as modified amino acids have been determined using
      state-of-the-art software, PEPstr. To facilitate users, various user-friendly web
      tools, for data fetching, analysis and browsing, have been integrated. We hope
      that ParaPep will be advantageous in designing therapeutic peptides against
      parasitic diseases. Database URL: http://crdd.osdd.net/raghava/parapep/ 

PMID- 24923819
TI  - Curation accuracy of model organism databases.
AB  - Manual extraction of information from the biomedical literature-or biocuration-is
      the central methodology used to construct many biological databases. For example,
      the UniProt protein database, the EcoCyc Escherichia coli database and the
      Candida Genome Database (CGD) are all based on biocuration. Biological databases
      are used extensively by life science researchers, as online encyclopedias, as
      aids in the interpretation of new experimental data and as golden standards for
      the development of new bioinformatics algorithms. Although manual curation has
      been assumed to be highly accurate, we are aware of only one previous study of
      biocuration accuracy. We assessed the accuracy of EcoCyc and CGD by manually
      selecting curated assertions within randomly chosen EcoCyc and CGD gene pages and
      by then validating that the data found in the referenced publications supported
      those assertions. A database assertion is considered to be in error if that
      assertion could not be found in the publication cited for that assertion. We
      identified 10 errors in the 633 facts that we validated across the two databases,
      for an overall error rate of 1.58%, and individual error rates of 1.82% for CGD
      and 1.40% for EcoCyc. These data suggest that manual curation of the experimental
      literature by Ph.D-level scientists is highly accurate. Database URL:
      http://ecocyc.org/, http://www.candidagenome.org// 

PMID- 24923820
TI  - Egas: a collaborative and interactive document curation platform.
AB  - With the overwhelming amount of biomedical textual information being produced,
      several manual curation efforts have been set up to extract and store concepts
      and their relationships into structured resources. As manual annotation is a
      demanding and expensive task, computerized solutions were developed to perform
      such tasks automatically. However, high-end information extraction techniques are
      still not widely used by biomedical research communities, mainly because of the
      lack of standards and limitations in usability. Interactive annotation tools
      intend to fill this gap, taking advantage of automatic techniques and existing
      knowledge bases to assist expert curators in their daily tasks. This article
      presents Egas, a web-based platform for biomedical text mining and assisted
      curation with highly usable interfaces for manual and automatic in-line
      annotation of concepts and relations. A comprehensive set of de facto standard
      knowledge bases are integrated and indexed to provide straightforward concept
      normalization features. Real-time collaboration and conversation functionalities
      allow discussing details of the annotation task as well as providing instant
      feedback of curator's interactions. Egas also provides interfaces for on-demand
      management of the annotation task settings and guidelines, and supports standard
      formats and literature services to import and export documents. By taking
      advantage of Egas, we participated in the BioCreative IV interactive annotation
      task, targeting the assisted identification of protein-protein interactions
      described in PubMed abstracts related to neuropathological disorders. When
      evaluated by expert curators, it obtained positive scores in terms of usability,
      reliability and performance. These results, together with the provided innovative
      features, place Egas as a state-of-the-art solution for fast and accurate
      curation of information, facilitating the task of creating and updating knowledge
      bases and annotated resources. Database URL: http://bioinformatics.ua.pt/egas. 

PMID- 24923821
TI  - IFIM: a database of integrated fitness information for microbial genes.
AB  - Knowledge of an organism's fitness for survival is important for a complete
      understanding of microbial genetics and effective drug design. Current essential
      gene databases provide only binary essentiality data from genome-wide
      experiments. We therefore developed a new database that Integrates quantitative
      Fitness Information for Microbial genes (IFIM). The IFIM database currently
      contains data from 16 experiments and 2186 theoretical predictions. The highly
      significant correlation between the experiment-derived fitness data and our
      computational simulations demonstrated that the computer-generated predictions
      were often as reliable as the experimental data. The data in IFIM can be accessed
      easily, and the interface allows users to browse through the gene fitness
      information that it contains. IFIM is the first resource that allows easy access
      to fitness data of microbial genes. We believe this database will contribute to a
      better understanding of microbial genetics and will be useful in designing drugs
      to resist microbial pathogens, especially when experimental data are unavailable.
      Database URL: http://cefg.uestc.edu.cn/ifim/ or http://cefg.cn/ifim/ 

PMID- 24923823
TI  - Editorial.

PMID- 24923822
TI  - MorusDB: a resource for mulberry genomics and genome biology.
AB  - Mulberry is an important cultivated plant that has received the attention of
      biologists interested in sericulture and plant-insect interaction. Morus
      notabilis, a wild mulberry species with a minimal chromosome number is an ideal
      material for whole-genome sequencing and assembly. The genome and transcriptome
      of M. notabilis were sequenced and analyzed. In this article, a web-based and
      open-access database, the Morus Genome Database (MorusDB), was developed to
      enable easy-to-access and data mining. The MorusDB provides an integrated data
      source and an easy accession of mulberry large-scale genomic sequencing and
      assembly, predicted genes and functional annotations, expressed sequence tags
      (ESTs), transposable elements (TEs), Gene Ontology (GO) terms, horizontal gene
      transfers between mulberry and silkworm and ortholog and paralog groups.
      Transcriptome sequencing data for M. notabilis root, leaf, bark, winter bud and
      male flower can also be searched and downloaded. Furthermore, MorusDB provides an
      analytical workbench with some built-in tools and pipelines, such as BLAST,
      Search GO, Mulberry GO and Mulberry GBrowse, to facilitate genomic studies and
      comparative genomics. The MorusDB provides important genomic resources for
      scientists working with mulberry and other Moraceae species, which include many
      important fruit crops. Designed as a basic platform and accompanied by the
      SilkDB, MorusDB strives to be a comprehensive platform for the silkworm-mulberry
      interaction studies. Database URL: http://morus.swu.edu.cn/morusdb. 

PMID- 24923824
TI  - Hoarding versus the immediate consumption of food among hamsters and gerbils.
AB  - This project dealt with a comparative analysis of the effects of food deprivation
      on feeding and hoarding in hamsters and gerbils. The animals were given food in
      their home cage and their food intake was measured during a 30-min period after
      which they were transferred to an apparatus in which hoarding behaviour was
      assessed. The results indicated interesting species differences in the animals'
      reactions in the test situations. Whereas food-deprived gerbils ate more food
      than nondeprived gerbils, the food intake of hamsters was not significantly
      enhanced by deprivation. In the hoarding test, although significant differences
      were observed between deprived and nondeprived gerbils, the absolute level of
      hoarding in gerbils was very low in comparison to that of hamsters tested under
      the same conditions. These results suggest that hamsters and gerbils respond to
      challenges to their food reserves with different strategies. 

PMID- 24923825
TI  - Prey capture by the cuttlefish (Sepia officinalis L): An experimental study of
      two strategies.
AB  - This study shows that the size of the prey (Carcinus maenas ) relative to the
      predator (Sepia officinalis ) is of importance in the choice between two types of
      attack: either capture by ejection of the two extensible tentacles, or capture by
      jumping on the prey. Small crabs are preferentially captured by the first method
      and large crabs by the second. Other factors which may explain the observed
      variations, include previous experience of the predator and the behaviour of the
      prey. 

PMID- 24923826
TI  - Classical heart-rate conditioning and differentiation of visual CS with an
      appetitive UCS in pigeons.
AB  - A tachycardic response was classically conditioned in thirsty pigeons using water
      as an unconditioned stimulus and localized lights as conditioned stimuli. This
      was successful in 6 out of 9 birds. In one experiment the subjects had their
      heads immobilized so that the positions of the stimuli within the visual field
      could be precisely specified. When the stimuli were shifted from the binocular to
      the monocular field and vice versa there was no initial transfer of a conditioned
      differentiation between a white and a green light. 

PMID- 24923827
TI  - Dominance and aggression in social groups of male and female rats.
AB  - Two experiments were performed to examine aggression and dominance in domestic
      male and female Rattus norvegicus living in small mixed-sex (3 males and 3
      females) groups. Experiment 1 examined the development of aggression in females.
      A single female (alpha) within each of the six colonies tested showed the
      preponderance of attacks on male intruders placed into the home-cage when male
      colony residents were absent. Over 12 weeks of intruder-aggression training
      female alphas showed only a mild nonsignificant elevation of aggressive behavior.
      A comparison of aggression of male and female colony alphas tested with opponents
      of each sex revealed that aggression was mainly directed at like-sex opponents,
      and that female attack was more defensive in character than male attack
      regardless of opponent sex. The highest intensity of aggression occurred when
      male alphas confronted male intruders. Although intruders never showed offense
      toward male residents, 61% of intruding males showed offense in response to
      attack by females. Experiment 2 investigated the relationship between aggressive
      dominance and competitive measures of dominance within each of 10 mixed-sex
      colonies. Alpha stat s of male and female colony residents did not reliably
      predict priority of access to food or water in tests of direct resource
      competition with like-sex colony members. When colony males were simultaneously
      tested for copulation, the copulatory behavior of alpha males was significantly
      greater than that of other colony males. Results are discussed in relation to the
      role of aggression in the reproductive strategy of male and female Rattus
      norvegicus . 

PMID- 24923828
TI  - Agonistic experience and individual recognition in male Quelea quelea.
AB  - Male Quelea were moved between groups to assess whether experience of winning or
      losing in new groups was correlated with their success in competition over food
      when they were returned to their original groups. No such effect was found.
      However, differences in time spent feeding after deprivation and in aggressive
      behaviour were found between groups depending on whether they were made up from
      high- or low-ranking individuals. In paired encounters there was no evidence that
      birds threatened unfamiliar individuals more than familiar ones or that they
      avoided sitting next to them more than familiar birds. This suggests that
      individual recognition, if it exists at all in these groups, is not important in
      their agonistic relationships. The rank birds occupied was correlated with beak
      colour, a probable measure of androgen levels, and with the amount of food
      consumed after deprivation. The latter result suggests that the same period of
      deprivation may affect some individuals more than others and this in turn may
      lead them to compete more for food. 

PMID- 24923829
TI  - Effects of repeated exposure to electric footshock on subsequent agonistic
      behaviour and adrenocortical secretion in male mice of different androgen status.
AB  - Two experiments were conducted to examine effects of repeated exposure to
      electric footshock on subsequent agonistic behaviour and adrenocortical secretion
      in male mice of different androgen status. Aggressive and submissive behavioural
      components were independently studied in the two experiments. It was found that
      repetition reduced aggressive, and stimulated submissive and adrenocortical
      responses to shock, particularly in castrates. The direction of the shock effects
      on aggressive behaviour was reversed by repetition in castrates, whereas only the
      magnitude of the behavioural responses was changed at normal androgen levels. It
      is suggested that the changes in agonistic responses to shock induced by
      repetition are mediated by changes in pituitary-adrenocortical secretion, and
      that androgen inhibits the shock effects on agonistic behaviour through
      inhibition of the pituitary-adrenocortical responses to shock. 

PMID- 24923830
TI  - Hypothalamic levels of thyrotropin-releasing hormone (TRH) in male albino mice of
      different social status.
AB  - Hypothalamic levels of TRH were contrasted in identified dominant and submissive
      (housed together for 4 days) Swiss male mice and undisturbed 'isolated'
      counterparts. Both dominants and submissives had significantly higher titres of
      this hormone than the 'isolates', suggesting that the experience of fighting
      relatively elevates the concentration of this factor in both winners and losers.
      It seems likely that titres of TRH are modified by fighting experience and these
      factors may alter subsequent behaviour but more investigation is needed on this
      topic. 

PMID- 24923831
TI  - A tilted rotational stimulation improves the gait of a cerebellar mutant mouse :
      The staggerer.
AB  - A titled rotational stimulation was given daily from birth to normal and
      cerebellar staggerer mutant mice. At weaning time the ability to ambulate on a
      holed floor was measured. An increase in neither the speed nor the total
      exploration was demonstrated but the ability to avoid holes was significantly
      improved for both groups. In this experiment, the mutant appeared to be more
      sensitive to the enrichment factor than the normal. 

PMID- 24923836
TI  - Agnes Richter's jacket.

PMID- 24923838
TI  - A method to identify and validate mitochondrial modulators using mammalian cells
      and the worm C. elegans.
AB  - Mitochondria are semi-autonomous organelles regulated by a complex network of
      proteins that are vital for many cellular functions. Because mitochondrial
      modulators can impact many aspects of cellular homeostasis, their identification
      and validation has proven challenging. It requires the measurement of multiple
      parameters in parallel to understand the exact nature of the changes induced by
      such compounds. We developed a platform of assays scoring for mitochondrial
      function in two complementary models systems, mammalian cells and C. elegans. We
      first optimized cell culture conditions and established the mitochondrial
      signature of 1,200 FDA-approved drugs in liver cells. Using cell-based and C.
      elegans assays, we further defined the metabolic effects of two pharmacological
      classes that emerged from our hit list, i.e. imidazoles and statins. We found
      that these two drug classes affect respiration through different and cholesterol
      independent mechanisms in both models. Our screening strategy enabled us to
      unequivocally identify compounds that have toxic or beneficial effects on
      mitochondrial activity. Furthermore, the cross-species approach provided novel
      mechanistic insight and allowed early validation of hits that act on
      mitochondrial function. 

PMID- 24923839
TI  - Health region development from the perspective of system theory - an empirical
      cross-regional case study.
AB  - Governments are increasingly establishing health regions to deal with current
      challenges of public health service. These regions are seen as instruments to
      balance public and private stakeholders, and offer health care to regional
      citizens as well as to medical/health tourists. However, it is still unclear how
      the development of such health regions as well as their governance may be
      conceptualized. We apply Luhmann's system theory approach in the context of a
      cross-regional case study that compares health region developments in the
      Autonomous Province of Bolzano-South Tyrol (Italy) with particular regard to the
      Eastern Dolomites and in the province of Zeeland (the Netherlands). We suggest
      that Luhmann's system theory provides a useful set of criteria to evaluate and
      judge health region development. Fully developed health regions can be understood
      as auto-poietic systems. By emphasizing programs, personnel, and communication
      channels, these case studies illustrate the suitability of the system theory
      toolset to analyze the governance and spatial embeddedness of health regions.
      Additionally, the study contributes to literature by indicating that health
      regions are closely related to identity issues and to decision making in regions.

PMID- 24923840
TI  - Impact of chronic kidney disease on myocardial blood flow regulation in dogs.
AB  - BACKGROUND/AIMS: Chronic kidney disease (CKD) increases cardiovascular risk
      possibly due to coronary microvessel dysfunction and impaired myocardial flow
      reserve. This study investigated the effects of CKD on the regulation and
      transmural distribution of myocardial blood flow along with oxygen demand during
      intravenous dobutamine-induced increases in cardiac work. METHODS: CKD was
      produced in dogs by a two-stage subtotal nephrectomy (kidney ablation-infarction
      model). Serum creatinine and blood urea nitrogen were evaluated during the
      development of CKD along with systemic blood pressure (tail-cuff
      plethysmography). After 5 weeks, the CKD dogs were staged according to the
      International Renal Interest Society staging system; all dogs were anesthetized
      and surgically prepared for blood flow studies. Data analyses were performed
      between sham control (CTR) and stage 1 and 2 CKD dogs. RESULTS: At baseline,
      myocardial blood flow and diastolic aortic pressure were similar for all groups.
      During intravenous dobutamine, myocardial blood flow was markedly higher than CTR
      even though hematocrit levels declined with the severity of CKD. In the CTR dogs,
      myocardial blood flow increased in direct relation to cardiac work. However, in
      the CKD dogs (stage 1 and 2), maximum blood flow was achieved with low-dose
      dobutamine, indicating that coronary autoregulation is more readily exhausted
      with minimal increases in cardiac work during CKD. CONCLUSION: We report that CKD
      markedly impairs coronary vascular reserve and myocardial blood flow regulation
      which could contribute to greater cardiovascular risk and poor clinical outcomes
      in CKD patients.

PMID- 24923837
TI  - Neuronal deletion of GSK3beta increases microtubule speed in the growth cone and
      enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2.
AB  - BACKGROUND: In the adult central nervous system, axonal regeneration is abortive.
      Regulators of microtubule dynamics have emerged as attractive targets to promote
      axonal growth following injury as microtubule organization is pivotal for growth
      cone formation. In this study, we used conditioned neurons with high regenerative
      capacity to further dissect cytoskeletal mechanisms that might be involved in the
      gain of intrinsic axon growth capacity. RESULTS: Following a phospho-site broad
      signaling pathway screen, we found that in conditioned neurons with high
      regenerative capacity, decreased glycogen synthase kinase 3beta (GSK3beta)
      activity and increased microtubule growth speed in the growth cone were present.
      To investigate the importance of GSK3beta regulation during axonal regeneration
      in vivo, we used three genetic mouse models with high, intermediate or no
      GSK3beta activity in neurons. Following spinal cord injury, reduced GSK3beta
      levels or complete neuronal deletion of GSK3beta led to increased growth cone
      microtubule growth speed and promoted axon regeneration. While several
      microtubule-interacting proteins are GSK3beta substrates, phospho-mimetic
      collapsin response mediator protein 2 (T/D-CRMP-2) was sufficient to decrease
      microtubule growth speed and neurite outgrowth of conditioned neurons and of
      GSK3beta-depleted neurons, prevailing over the effect of decreased levels of
      phosphorylated microtubule-associated protein 1B (MAP1B) and through a mechanism
      unrelated to decreased levels of phosphorylated cytoplasmic linker associated
      protein 2 (CLASP2). In addition, phospho-resistant T/A-CRMP-2 counteracted the
      inhibitory myelin effect on neurite growth, further supporting the GSK3beta-CRMP
      2 relevance during axon regeneration. CONCLUSIONS: Our work shows that increased
      microtubule growth speed in the growth cone is present in conditions of increased
      axonal growth, and is achieved following inactivation of the GSK3beta-CRMP-2
      pathway, enhancing axon regeneration through the glial scar. In this context, our
      results support that a precise control of microtubule dynamics, specifically in
      the growth cone, is required to optimize axon regrowth.

PMID- 24923841
TI  - Innovative method and equipment for personalized ventilation.
AB  - At the University of Debrecen, a new method and equipment for personalized
      ventilation has been developed. This equipment makes it possible to change the
      airflow direction during operation with a time frequency chosen by the user. The
      developed office desk with integrated air ducts and control system permits
      ventilation with 100% outdoor air, 100% recirculated air, or a mix of outdoor and
      recirculated air in a relative proportion set by the user. It was shown that
      better comfort can be assured in hot environments if the fresh airflow direction
      is variable. Analyzing the time step of airflow direction changing, it was found
      that women prefer smaller time steps and their votes related to thermal comfort
      sensation are higher than men's votes. 

PMID- 24923842
TI  - High prevalence of maternal hypothyroidism despite adequate iodine status in
      Indian pregnant women in the first trimester.
AB  - BACKGROUND: Iodine requirements are increased during pregnancy to maintain
      maternal and fetal euthyroidism. There have been recent improvements in iodized
      salt coverage in India, but whether iodized salt is sufficient to sustain iodine
      requirements during pregnancy remains uncertain. Our aims were to measure thyroid
      status in first trimester pregnant women in southern India and assess potential
      determinants of thyroid function, including iodine status, thyroid autoimmunity,
      dietary patterns, body weight, and anemia. METHODS: This was a cross-sectional
      study among 334 pregnant women of <= 14 weeks' gestation, in Bangalore, India. We
      measured anthropometrics, urinary iodine concentration (UIC), maternal thyroid
      volume (by ultrasound), and thyroid function. We applied a thyrotropin (TSH)
      upper limit of 2.5 mIU/L to classify thyroid insufficiency. Using a
      questionnaire, we obtained sociodemographic and dietary data, obstetric history,
      and use of iodized salt and iodine supplements. RESULTS: Among the women, the
      mean (standard deviation) gestational age was 10.3 (2.5) weeks, 67% were
      nulliparous, 21% were vegetarian, 19% were anemic, and 23% were overweight or
      obese. Iodized salt was used by 98% of women, and they were iodine sufficient:
      median UIC (range) was 184.2 MUg/L (8.1-1152 MUg/L) and all had a normal thyroid
      volume. However, 18% of the women had thyroid insufficiency: 3.7% had overt
      hypothyroidism (83% with positive TPO-Ab), 9.2% had subclinical hypothyroidism,
      and 5.2% had hypothyroxinemia. Women consuming vegetarian diets did not have
      significantly lower iodine intakes or higher risk of hypothyroidism than those
      consuming mixed diets, but overweight/obesity and anemia predicted thyroid
      insufficiency. CONCLUSION: In this urban population of southern India, pregnant
      women have adequate iodine status in the first trimester. Despite this, many have
      thyroid insufficiency, and the prevalence of overt hypothyroidism is more than
      fivefold higher than reported in other iodine sufficient populations of pregnant
      women.

PMID- 24923843
TI  - Multiple cerebral sinus thromboses complicating meningococcal meningitis: a
      pediatric case report.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVT) is a rare and potentially life
      threatening condition in the pediatric population. The clinical presentation is
      frequently nonspecific; thus diagnosis is often delayed or missed. CASE
      PRESENTATION: A previously healthy 8 month-old boy was diagnosed with
      meningococcal meningitis. At hospital admission, an urgent non contrast-enhanced
      computed tomography (CT) of the head and neck was performed with normal results.
      Ceftriaxone was promptly started and the clinical condition of the patient
      improved. However, on the 7th day of hospitalization, the child suddenly
      manifested irritability and lethargy. An urgent contrast-enhanced CT of the head
      and neck was immediately performed, revealing thrombosis of the superior
      sagittal, transverse and rectus sinuses. A thrombophilic evaluation was
      performed, revealing hyperhomocysteinemia and methylenetetrahydrofolate reductase
      (MTHFR) variants (C677T and A1298C). CONCLUSIONS: The causes of CVT may be
      categorized into three main groups: hypercoagulable states, conditions causing
      blood flow disturbances, and all causes of inflammation or infection. In this
      case report, we observed more than one risk factor that predisposed the patient
      to CVT. Consequently, even if a causative factor is detected, a thrombophilic
      blood evaluation should be performed. In fact, in case of a prothrombotic
      condition, the patient's family should be advised that prompt administration of
      anticoagulant is necessary in the event of situations that could lead to
      thrombosis. Finally, CVT may be considered a possible complication of infection
      even when recent imaging results are normal. A prompt CVT diagnosis is required
      to obtain a good outcome. Delayed diagnosis is mainly due to the rarity of the
      disease and physicians' unawareness of this type of complication.

PMID- 24923844
TI  - Liver Selective Internal Radiation Therapy with (90)Y resin microspheres:
      comparison between pre-treatment activity calculation methods.
AB  - Different methods to calculate (90)Y resin microspheres activity for Selective
      Internal Radiation Therapy (SIRT) were compared. Such comparison is not yet
      available and is needed in clinical practice to optimize patient specific
      treatment planning. 32 (99m)Tc-macroagregates (MAA) evaluations were performed,
      followed by 26 treatments. Four methods to calculate (90)Y-activity were applied
      retrospectively: three based on Body Surface Area and one based on MIRD
      formalism, partition model (PM). Relationships between calculated activities,
      lung breakthrough (LB), the activity concentration ratio between lesions and
      healthy liver (T/N) and tumour involvement were investigated, where lobar and
      whole liver treatments were analysed separately. Without attenuation correction,
      overestimation of LB was 65%. In any case, the estimated lungs' doses remained
      below 30 Gy. Thus, the maximal injectable activity (MIA) is not limited by lungs'
      irradiation. Moreover, LB was not significantly related to T/N, neither to tumour
      involvement nor radiochemical purity (RP). Differences in calculated activity
      with the four methods were extremely large, in particular they were greater
      between BSA-based and PM activities for lobar treatments (from -85% to 417%)
      compared to whole liver treatments (from -49% to 61%). Two values of T/N ratio
      were identified as thresholds: for BSA-based methods, healthy liver doses are
      much higher than 30 Gy when T/N < 3; for PM, tumour doses are higher than 120 Gy
      when T/N > 4. As PM accounts for uptake ratio between normal and tumour liver,
      this method should be employed over BSA-based methods. 

PMID- 24923845
TI  - Lactose intolerance is not the cause of gastrointestinal adverse effects in beta
      thalassemia patients treated with deferasirox.

PMID- 24923847
TI  - Disturbance of larval orientation in Spodoptera frugiperda (Lepidoptera :
      Noctuidae) by microsurgical removal of endocrine centres.
AB  - The larvae of S. frugiperda showed differences in orientation depending largely
      upon their physiological states. A preference for wet conditions manifested
      itself in the orientation of the penultimate instar larvae, whereas the larvae of
      the final stage exhibited preference neither for wet nor for dry conditions.
      However, the 'light level' proved to be of prime importance in the final stage,
      such that it drove the larvae almost exclusively to the dark, while it appeared
      to be of secondary importance in the preceding stage where the larvae only
      responded photopositively if deprived of the humidity-preference. Microsurgical
      removal of the medial neurosecretory cells in the pars intercerebralis resulted
      in a preference for dry conditions in both larval instars concomitant with an
      appreciable increase in the total water content of the larvae. The normal
      situation could be easily restored by implantation of some active cells.
      Allatectomy failed to alter the normal preferences of the final instar larvae,
      whereas it induced a humidity-preference in the larvae of the penultimate stage,
      a response exhibited normally by intact larvae of the final stage. This result
      might suggest the implication of the morphogenetic hormones in some way or
      another in the control of larval response to the 'humidity level'. However,
      photopreference in both larval instars appeared to be genetically controlled. 

PMID- 24923846
TI  - Fisetin inhibits high-glucose-induced vascular inflammation in vitro and in vivo.
AB  - AIM AND OBJECTIVE: Fisetin, an active compound isolated from flowering plants in
      the family Fabaceae, was reported to have antiviral, neuroprotective, and anti
      inflammatory effects. Vascular inflammatory processes have been suggested to play
      key roles in the initiation and progression of atherosclerosis, a major
      complication of diabetes mellitus. Thus, we determined the ability of fisetin to
      suppress vascular inflammatory processes induced by high glucose (HG) in primary
      human umbilical vein endothelial cells (HUVECs) and mice. METHODS: The effects of
      fisetin on HG-induced vascular inflammation were determined by measuring vascular
      permeability, leukocyte adhesion and migration, cell adhesion molecule (CAM)
      expression levels, reactive oxygen species (ROS) formation, and nuclear factor
      (NF)-kappaB activation. RESULTS: HG markedly increased vascular permeability,
      monocyte adhesion, expressions of CAMs, formation of ROS, and activation of NF
      kappaB. Remarkably, all of the observed vascular inflammatory effects induced by
      HG were inhibited by pretreatment with fisetin. CONCLUSION: Vascular inflammatory
      responses induced by HG are critical events underlying the development of
      diabetic complications; therefore, our results suggest that fisetin possesses
      significant therapeutic effects against diabetic complications and
      atherosclerosis.

PMID- 24923848
TI  - Central control of mating call production and spawning in the tree frog Hyla
      arborea savignyi (Audouin): Results of electrical stimulation of the brain.
AB  - Electrical stimulation of the anterior preoptic nucleus elicited the production
      of mating calls by male Hyla arborea savignyi. Such calls are composed of pulses
      resembling those of natural mating calls both in their duration and in their
      sequential arrangement. As a rule, the amplitude of successive pulses within a
      group increases more rapidly in the electrically evoked calls than in natural
      calls. The frogs could be brought into a state of readiness to call, which did
      not lead to actual calling activity, by stimulation in the anterior preoptic,
      posterior preoptic, and magnocellular nuclei as well as in the hypothalamus.
      Stimulation of the anterior preoptic nucleus of one female elicited repeated
      vocalizations, which may be interpretable as mating calls. The posture adopted by
      the female for spawning can be elicited in males as well as in females by
      electrical stimulation of the anterior preoptic nucleus. 

PMID- 24923849
TI  - Attempt to modify rate and duration of licking in rats by operant conditioning.
AB  - Lick-rate in rats is said to be constant for a given animal, despite variations
      of internal and external stimuli. On the other hand, small changes can be
      observed due to changes in the construction of the licking device. However,
      variations do not exceed 20%. In an attempt to gain operant control over the ILI
      (interlick interval - the time between two lick-onsets) the delivery of
      reinforcement (20 MUl water) was made dependent on the emission of ILIs of a
      predetermined length longer than during baseline licking. It could be observed
      that rats could not shift the peak of their ILI distribution within the
      reinforced range but - to increase the number of reinforcements - they increased
      the scatter of the ILI distribution or developed a "harmonic" peak at double ILI
      length. When the animals were forced in a second experiment to prolong the lick
      duration (time of tongue-spout contact) to obtain water, they failed if the
      restriction from the drinking spout made a closer approach impossible. It is
      argued that the ability to obtain reinforcement under both schedules is due to
      postural changes of the animal. The mechanisms controlling licking seem to be
      relatively constant, which allows good coordination with other behaviours which
      have to be performed during drinking, such as breathing and swallowing. It can be
      concluded that the amount of water consumed by rats is controlled by the length
      of time spent in licking and not by changing the lick-rate. 

PMID- 24923850
TI  - A quantitative study of copulatory behaviour of large Felidae.
AB  - A total of 109 copulations was observed in six male-female pairs from four
      species of large Felidae. The mean intromission durations were 3.0 sec for Asian
      leopards (Panthera pardus), 3.3 sec for African leopards (Panthera pardus), 12.9
      sec for snow leopards (Uncia uncia), 2.3 sec for spotted jaguars (Panthera onca),
      3.3 sec for black jaguars (Panthera onca), and 12.4 sec for Siberian tigers
      (Panthera tigris). Behavioural patterns were qualitatively similar across
      species; all displayed a copulatory pattern with no lock, no intra-vaginal
      thrusting, ejaculation on a single insertion, and multiple ejaculations. Whereas
      domestic cats are reported to assume a neck grip and to tread prior to insertion,
      these larger Felidae generally did so after intromission had been achieved. After
      copulation, females of some pairs swiped at the male and displayed a rolling
      after-reaction. 

PMID- 24923851
TI  - Sex differences in nonhuman primate grooming.
AB  - In this article, sex differences in nonhuman primate social grooming are
      reviewed. In general, female nonhuman primates groom more than do males. This
      conclusion is tempered somewhat by acknowledgements of exceptions and
      qualifications, and by evidence for experiential control of grooming. 

PMID- 24923852
TI  - Quantitative studies of schizophrenic behavior.
AB  - Behavioral data from eight psychiatric patients were collected and formed into 14
      time series of 100 weekly rates (percentages of positive entries for frequent
      behaviors such as pacing, talking, hand-movement, etc.). A variety of methods of
      time-series analysis were applied to determine optimal predictive schemes in an
      effort to develop an inductive approach to input-output behavioral modelling.
      Some attempts at numerical prediction into new data were successful, and the
      results suggested that the best overall approach is likely to be nonlinear
      modification of auto-regressive schemes. Nonlinearity and nonstationarity of such
      time series are prominent features, but deterministic trends appear strong enough
      to justify extensive work. Application of artificial inputs to some of the models
      suggests that protracted oscillatory responses to stimulation may be
      characteristic for some schizophrenic patients. 

PMID- 24923856
TI  - MicroRNA-224 upregulation and AKT activation synergistically predict poor
      prognosis in patients with hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Previous evidence has shown that microRNA (miR)-224 may
      function as an onco-miRNA in hepatocellular carcinoma (HCC) cells by activating
      AKT signaling. However, little is known about the clinical significance of the
      combined expression of miR-224 and phosphorylated-AKT (pAKT) on human HCC. The
      aim of this study was to investigate the synergistical influence of miR-224 and
      pAKT on clinical characteristics and prognosis in patients with HCC. METHODS: One
      hundred and thirty HCC patients who had undergone curative liver resection were
      selected. In situ hybridization and immunohistochemistry were respectively
      performed to detect the expression of miR-224 and pAKT in the respective tumors.
      RESULTS: Compared with the adjacent nonneoplastic liver tissues, the expression
      levels of miR-224 and pAKT protein in HCC tissues were both significantly
      increased (both P<0.001). In addition, the combined upregulation of miR-224 and
      pAKT protein was significantly associated with serum AFP (P=0.01), tumor stage
      (P=0.002) and tumor grade (P=0.008). Moreover, HCC patients highly expressing
      both miR-224 and pAKT protein had worse 5-year disease-free survival and 5-year
      overall survival (both P<0.001). Furthermore, the Cox proportional hazards model
      showed that the combined upregulation of miR-224 and pAKT protein (miR-224
      high/pAKT-high) may be independent poor prognostic factors for both 5-year
      disease-free survival (P=0.008) and 5-year overall survival (P=0.01) in HCC.
      CONCLUSION: These results indicate for the first time that miR-224 upregulation
      and AKT activation may synergistically associate with tumor progression of HCC.
      The combined high expression of miR-224 and pAKT may be a potential indicator for
      predicting unfavorable prognosis in HCC patients.

PMID- 24923857
TI  - Incidence of bone metastases and survival after a diagnosis of bone metastases in
      breast cancer patients.
AB  - BACKGROUND: Bone is the most common metastatic site associated with breast
      cancer. Using a database of women with breast cancer treated at Guy's Hospital,
      London 1976-2006 and followed until end 2010, we determined incidence of and
      survival after bone metastases. METHODS: We calculated cumulative incidence of
      bone metastases considering death without prior bone metastases as a competing
      risk. Risk of bone metastases was modelled through Cox-regression. Survival after
      bone metastases diagnosis was calculated using Kaplan-Meier methodology. RESULTS:
      Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean).
      Incidence of bone metastases was significantly higher in younger women, tumour
      size >5 cm, higher tumour grade, lobular carcinoma and >= four positive nodes,
      but was not affected by hormone receptor status. Median survival after bone
      metastases diagnosis was 2.3 years in women with bone-only metastases compared
      with <1 year in women with visceral and bone metastases. There was a trend for
      decreased survival for patients who developed visceral metastases early, and
      proportionately fewer patients in this group. INTERPRETATION: Incidence of bone
      metastases has decreased but bone metastases remain a highly relevant clinical
      problem due to the large number of patients being diagnosed with breast cancer.

PMID- 24923858
TI  - Intrinsic optical properties and enhanced plasmonic response of epitaxial silver.
AB  - Using atomically smooth epitaxial silver films, new optical permittivity
      highlighting significant loss reduction in the visible frequency range is
      extracted. Largely enhanced propagation distances of surface plasmon polaritons
      are measured, confirming the low intrinsic loss in silver. The new permittivity
      is free of extrinsic spectral features associated with grain boundaries and
      localized plasmons inevitably present in thermally deposited films. 

PMID- 24923860
TI  - Assessment of proteasome concentration and chymotrypsin-like activity in plasma
      of patients with newly diagnosed multiple myeloma.
AB  - The ubiquitin-proteasome pathway is implicated in the pathogenesis of many
      haematologic malignancies, including multiple myeloma. Under conditions of rapid
      cell turnover and growth rate, proteasomes are returned into circulation. The
      measurement of their levels or activity could offer a new approach to diagnosis,
      prognosis and monitoring of anticancer treatment in carcinoma patients. We
      analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in the
      plasma of 64 patients with a newly diagnosed multiple myeloma and 30 healthy
      volunteers. The values were found to be significantly higher in the studied
      patients and advanced disease stages compared to the control group, and decreased
      significant after chemotherapy. Both proteasome concentration and ChT-L activity
      correlated with adverse prognostic factors, such as lactate dehydrogenase and
      beta2-macroglobulin. We also showed that proteasome concentration positively
      correlates with IL-6 level, as opposed to proteasome ChT-L activity. Of note,
      higher proteasome ChT-L activity, unlike the concentration, was proved to be an
      indicator of a shorter progression free survival, constituting thereby an
      important prognostic marker. 

PMID- 24923859
TI  - Depression in Cardiovascular Patients in Middle Eastern Populations: A Literature
      Review.
AB  - Cardiovascular disease (CVD) is increasing in Middle Eastern countries.
      Depression is associated with increased morbidity and mortality rates among
      cardiovascular (CV) patients. Early detection of and intervention for depression
      among CV patients can reduce morbidity and mortality and save health care costs.
      Public information on mental health care needs of Arab CV patients living in
      Middle East regions is scattered and limited. This literature review surveyed and
      summarized research studies to learn what is known about the relationship between
      depression and CVD in Middle Eastern populations. The information will raise
      awareness among health care professionals and policy makers regarding the
      clinical significance of depression in Arab CV patients. It might contribute to
      development of culturally appropriate and effective mental health care services.
      Multiple databases were searched and 60 articles were assessed, including studies
      that investigated depression in Arab CV patient populations, physiological
      mechanisms of depression-CVD comorbidity, and intervention strategies that affect
      CV risk in depressed Arab patients. We discuss the extent to which this issue has
      been explored in Arab populations living in Middle East regions and Arab
      populations living abroad. We recommend that more comprehensive and in-depth
      research studies be conducted with Arab cardiac patients to enable implementation
      of culturally appropriate and effective mental health care interventions. 

PMID- 24923861
TI  - Cell line cross-contamination: WSU-CLL is a known derivative of REH and is
      unsuitable as a model for chronic lymphocytic leukaemia.

PMID- 24923862
TI  - Lack of shared decision making in cancer screening discussions: results from a
      national survey.
AB  - BACKGROUND: Clinicians are encouraged to support patients in achieving shared
      decision making (SDM) for cancer screening. PURPOSE: To describe decision making
      processes and outcomes for cancer screening discussions. METHODS: A 2011 national
      Internet survey of adults aged >=50 years who made cancer screening decisions
      (breast, BrCa; colorectal, CRC; prostate, PCa) within the previous 2 years was
      conducted. Participants were asked about their perceived cancer risk; how
      informed they felt about cancer tests; whether their healthcare provider
      addressed pros/cons of testing, presented the option of no testing, and elicited
      their input; whether they were tested; and their confidence in the screening
      decision. Data were analyzed in 2013-2014 with descriptive statistics and
      logistic regression. RESULTS: Overall, 1,134 participants (477 men, 657 women)
      aged >=50 years made cancer screening decisions, and 1,098 (354, BrCa; 598, CRC;
      146, PCa) decisions were discussed with a healthcare provider. Most discussions
      (51%-67%) addressed pros of screening some or a lot, but few (7%-14%) similarly
      addressed cons. For all cancer screening decisions, providers usually (63%-71%)
      explained that testing was optional, but less often asked women (43%-57%) than
      men (70%-71%) whether they wanted testing. Only 27%-38% of participants reported
      SDM, 69%-93% underwent screening, and 55%-76% would definitely make the same
      decision again. Perceived high/average cancer risk and feeling highly informed
      were associated with confidence in the screening decision. CONCLUSIONS:
      Discussions often failed to provide balanced information and meet SDM criteria.
      Supporting SDM could potentially improve the quality of cancer screening
      decisions.

PMID- 24923863
TI  - Firearm prohibition for persons convicted of violent crimes: a potential non
      legislative approach.

PMID- 24923864
TI  - Polypharmacology rescored: protein-ligand interaction profiles for remote binding
      site similarity assessment.
AB  - Detection of remote binding site similarity in proteins plays an important role
      for drug repositioning and off-target effect prediction. Various non-covalent
      interactions such as hydrogen bonds and van-der-Waals forces drive ligands'
      molecular recognition by binding sites in proteins. The increasing amount of
      available structures of protein-small molecule complexes enabled the development
      of comparative approaches. Several methods have been developed to characterize
      and compare protein-ligand interaction patterns. Usually implemented as
      fingerprints, these are mainly used for post processing docking scores and (off
      )target prediction. In the latter application, interaction profiles detect
      similarities in the bound interactions of different ligands and thus identify
      essential interactions between a protein and its small molecule ligands.
      Interaction pattern similarity correlates with binding site similarity and is
      thus contributing to a higher precision in binding site similarity assessment of
      proteins with distinct global structure. This renders it valuable for existing
      drug repositioning approaches in structural bioinformatics. Current methods to
      characterize and compare structure-based interaction patterns - both for protein
      small-molecule and protein-protein interactions - as well as their potential in
      target prediction will be reviewed in this article. The question of how the set
      of interaction types, flexibility or water-mediated interactions, influence the
      comparison of interaction patterns will be discussed. Due to the wealth of
      protein-ligand structures available today, predicted targets can be ranked by
      comparing their ligand interaction pattern to patterns of the known target. Such
      knowledge-based methods offer high precision in comparison to methods comparing
      whole binding sites based on shape and amino acid physicochemical similarity. 

PMID- 24923865
TI  - ABC transporters in adaptive immunity.
AB  - BACKGROUND: ABC transporters ubiquitously found in all kingdoms of life move a
      broad range of solutes across membranes. Crystal structures of four distinct
      types of ABC transport systems have been solved, shedding light on different
      conformational states within the transport process. Briefly, ATP-dependent
      flipping between inward- and outward-facing conformations allows directional
      transport of various solutes. SCOPE OF REVIEW: The heterodimeric transporter
      associated with antigen processing TAP1/2 (ABCB2/3) is a crucial element of the
      adaptive immune system. The ABC transport complex shuttles proteasomal
      degradation products into the endoplasmic reticulum. These antigenic peptides are
      loaded onto major histocompatibility complex class I molecules and presented on
      the cell surface. We detail the functional modules of TAP, its ATPase and
      transport cycle, and its interaction with and modulation by other cellular
      components. In particular, we emphasize how viral factors inhibit TAP activity
      and thereby prevent detection of the infected host cell by cytotoxic T-cells.
      MAJOR CONCLUSIONS: Merging functional details on TAP with structural insights
      from related ABC transporters refines the understanding of solute transport.
      Although human ABC transporters are extremely diverse, they still may employ
      conceptually related transport mechanisms. Appropriately, we delineate a working
      model of the transport cycle and how viral factors arrest TAP in distinct
      conformations. GENERAL SIGNIFICANCE: Deciphering the transport cycle of human ABC
      proteins is the major issue in the field. The defined peptidic substrate, various
      inhibitory viral factors, and its role in adaptive immunity provide unique tools
      for the investigation of TAP, making it an ideal model system for ABC
      transporters in general. This article is part of a Special Issue entitled
      Structural biochemistry and biophysics of membrane proteins.

PMID- 24923867
TI  - Iron deficiency in heart failure.

PMID- 24923868
TI  - Exploring the longitudinal relationships between the use of grammar in text
      messaging and performance on grammatical tasks.
AB  - Research has demonstrated that use of texting slang (textisms) when text
      messaging does not appear to impact negatively on children's literacy outcomes
      and may even benefit children's spelling attainment. However, less attention has
      been paid to the impact of text messaging on the development of children's and
      young people's understanding of grammar. This study therefore examined the
      interrelationships between children's and young adults' tendency to make
      grammatical violations when texting and their performance on formal assessments
      of spoken and written grammatical understanding, orthographic processing and
      spelling ability over the course of 1 year. Zero-order correlations showed
      patterns consistent with previous research on textism use and spelling, and there
      was no evidence of any negative associations between the development of the
      children's performance on the grammar tasks and their use of grammatical
      violations when texting. Adults' tendency to use ungrammatical word forms ('does
      you') was positively related to performance on the test of written grammar.
      Grammatical violations were found to be positively associated with growth in
      spelling for secondary school children. However, not all forms of violation were
      observed to be consistently used in samples of text messages taken 12 months
      apart or were characteristic of typical text messages. The need to differentiate
      between genuine errors and deliberate violation of rules is discussed, as are the
      educational implications of these findings. 

PMID- 24923866
TI  - Barriers to biomedical care and use of traditional medicines for treatment of
      cervical cancer: an exploratory qualitative study in northern Uganda.
AB  - Use of traditional medicines for treatment of cancers has increased worldwide. We
      used a qualitative approach to explore barriers to biomedical care and reasons
      for use of traditional medicines for the treatment of cervical cancer in Gulu,
      northern Uganda. We carried out 24 focus group discussions involving men and
      women aged 18-59 years. We employed content analyses technique in data analysis.
      Traditional medicines were used mainly due to barriers to biomedical care for
      cervical cancer. The barriers included health system factors, for example long
      distances to health facilities and unavailability of medicines; health workers'
      factors, for example negative attitudes towards patients and demands for bribes;
      individual patient's factors, for example inability to pay for medical care; and
      socio-cultural beliefs about superiority of traditional medicines and perceived
      greater privacy in accessing traditional healers. Barriers to biomedical care and
      community beliefs in the effectiveness of traditional medicines encourage use of
      traditional medicines for treatment of cervical cancer but might hinder help
      seeking at biomedical facilities. There is need for targeted culturally sensitive
      awareness campaign to promote effectiveness of modern medicine and to encourage
      cautious use of traditional medicines in the treatment of cervical cancer. 

PMID- 24923869
TI  - Role of free fatty acid receptors in the regulation of energy metabolism.
AB  - Free fatty acids (FFAs) are energy-generating nutrients that act as signaling
      molecules in various cellular processes. Several orphan G protein-coupled
      receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play
      important physiological roles in various diseases. FFA ligands are obtained from
      food sources and metabolites produced during digestion and lipase degradation of
      triglyceride stores. FFARs can be grouped according to ligand profiles, depending
      on the length of carbon chains of the FFAs. Medium- and long-chain FFAs activate
      FFA1/GPR40 and FFA4/GPR120. Short-chain FFAs activate FFA2/GPR43 and FFA3/GPR41.
      However, only medium-chain FFAs, and not long-chain FFAs, activate GPR84
      receptor. A number of pharmacological and physiological studies have shown that
      these receptors are expressed in various tissues and are primarily involved in
      energy metabolism. Because an impairment of these processes is a part of the
      pathology of obesity and type 2 diabetes, FFARs are considered as key therapeutic
      targets. Here, we reviewed recently published studies on the physiological
      functions of these receptors, primarily focusing on energy homeostasis. 

PMID- 24923870
TI  - Intermolecular interactions between molecules in various conformational states:
      the dimer of oxalic acid.
AB  - We considered stability of the dimer of oxalic acid. The global minimum energy
      structure identified by us is stabilized by two inter- and four intramolecular
      hydrogen bonds, whereas the most stable structure identified in previous studies
      is supported by two inter- and three intramolecular hydrogen bonds. The latter
      structure proves to be less stable by 25 meV than the former. The global minimum
      stability results from a balancing act between a moderately attractive two-body
      interaction energy and small repulsive one-body terms. We have analyzed zero
      point vibrational corrections to the stability of various conformers of oxalic
      acid and their dimers. We have found that minimum energy structures with the most
      stabilizing sets of hydrogen bonds have the largest zero-point vibrational
      energy, contrary to a naive anticipation based on red shifts of OH stretching
      modes involved in hydrogen bonds. 

PMID- 24923871
TI  - Caregivers provide more labeling responses to infants' pointing than to infants'
      object-directed vocalizations.
AB  - Existing studies have observed a robust relationship between infants' pointing
      gestures and language outcomes. By contrast, infants' overall vocal production is
      not related to language outcomes. One possible explanation for the association
      between pointing and language is that pointing gestures, as compared to
      vocalizations, may elicit more verbal responses from social partners that are
      facilitative for language learning. To test this, we observed forty-seven infants
      aged 1;0 during free play with their mothers and fathers separately to compare
      parents' verbal responses to infants' pointing gestures and object-directed
      vocalizations. Results showed that, compared to object-directed vocalizations,
      infants' pointing elicited more verbal responses from parents, particularly
      object labels. Moreover, mothers were more likely than fathers to provide labels.
      These results may help explain why pointing is associated with indices of
      language acquisition, but the production of vocalizations is not. 

PMID- 24923872
TI  - Factors affecting surgical outcome of endoscopic third ventriculostomy in
      congenital hydrocephalus.
AB  - Endoscopic third ventriculostomy (ETV) is an accepted modality of treatment for
      obstructive hydrocephalus, with good results in adult patients. However in the
      pediatric age group results vary from poor to similar to the adult population.
      This study evaluates the outcome of ETV in congenital hydrocephalus of both early
      and delayed presentation, and investigates factors that determine the outcome.
      Patients with congenital hydrocephalus who underwent ETV between January 2006 and
      December 2011 were retrospectively analyzed. Any conditions potentially
      influencing the need for redo surgery (persistent cerebrospinal fluid [CSF] leak
      not responding to local measures, tense fontanelle, increased ventricular size,
      recurrence of symptoms or radiological evidence of failure) were analyzed. A
      total of 102 patients with a mean age of 7.45years were included. Presenting
      features were increasing head circumference and delayed milestones. Ninety-eight
      patients had triventricular hydrocephalus due to aqueductal stenosis. Procedures
      performed were ETV only (n=74), ETV with aqueductoplasty (n=22), ETV with
      cystoventriculostomy (n=2) and aqueductoplasty only (n=2). Failure of ETV
      occurred in 11 patients and all were managed with a ventriculoperitoneal shunt.
      CSF leak in the perioperative period was the only factor that was significantly
      associated with failure of ETV. ETV is a safe procedure with a good success rate
      and can be offered to children with aqueductal stenosis. There is a higher chance
      of failure if there is a CSF leak in the early or late postoperative period.

PMID- 24923873
TI  - The role of receipt and timeliness of treatment in socioeconomic inequalities in
      lung cancer survival: population-based, data-linkage study.
AB  - BACKGROUND: Lung cancer survival is socioeconomically patterned, and
      socioeconomic inequalities in receipt of treatment have been demonstrated. In
      England, there are target waiting times for the referral (14 days) and treatment
      intervals (31 days from diagnosis, 62 days from GP referral). Socioeconomic
      inequalities in the time intervals from GP referral have been found. Cancer
      registry, Hospital Episode Statistics and lung cancer audit data were linked in
      order to investigate the contribution of these inequalities to socioeconomic
      inequalities in lung cancer survival. METHODS: Logistic regression was used to
      examine the likelihood of being alive 2 years after diagnosis, by socioeconomic
      position, for 22,967 lung cancer patients diagnosed in 2006-2009, and in a subset
      with stage recorded (n=5233). RESULTS: Socioeconomic inequalities in survival
      were found in a multivariable analysis adjusted for age, sex, histology, year,
      timely GP referral, performance status and comorbidity, with those in the most
      deprived socioeconomic group significantly less likely to be alive after 2 years
      (OR=0.77, 95% CI 0.66 to 0.88, p<0.001). When receipt of treatment was included
      in the analysis, the association no longer remained significant (OR=0.87, 95% CI
      0.75 to 1.00, p=0.06). Addition of timeliness of treatment did not alter the
      conclusion. Patients treated within guideline targets had lower likelihood of two
      year survival. CONCLUSIONS: Socioeconomic inequalities in survival from lung
      cancer were statistically explained by socioeconomic inequalities in receipt of
      treatment, but not by timeliness of referral and treatment. Further research is
      required to determine the currently unexplained socioeconomic variance in
      treatment rates.

PMID- 24923874
TI  - Case-based discussion from North Tyneside General Hospital: somatostatin
      analogues in yellow nail syndrome associated with recurrent pleural effusions.

PMID- 24923875
TI  - Navigated transcranial magnetic stimulation improves the treatment outcome in
      patients with brain tumors in motor eloquent locations.
AB  - BACKGROUND: Neurological and oncological outcomes of motor eloquent brain-tumor
      patients depend upon the ability to localize functional areas and the respective
      proposed therapy. We set out to determine whether the use of navigated
      transcranial magnetic stimulation (nTMS) had an impact on treatment and outcome
      in patients with brain tumors in motor eloquent locations. METHODS: We enrolled
      250 consecutive patients and compared their functional and oncological outcomes
      to a matched pre-nTMS control group (n = 115). RESULTS: nTMS mapping results
      disproved suspected involvement of primary motor cortex in 25.1% of cases,
      expanded surgical indication in 14.8%, and led to planning of more extensive
      resection in 35.2% of cases and more restrictive resection in 3.5%. In comparison
      with the control group, the rate of gross total resections increased
      significantly from 42% to 59% (P < .05). Progression-free-survival for low grade
      glioma was significantly better in the nTMS group at 22.4 months than in control
      group at 15.4 months (P < .05). Integration of nTMS led to a nonsignificant
      change of postoperative deficits from 8.5% in the control group to 6.1% in the
      nTMS group. CONCLUSIONS: nTMS provides crucial data for preoperative planning and
      surgical resection of tumors involving essential motor areas. Expanding surgical
      indications and extent of resection based on nTMS enables more patients to
      undergo surgery and might lead to better neurological outcomes and higher
      survival rates in brain tumor patients. The impact of this study should go far
      beyond the neurosurgical community because it could fundamentally improve
      treatment and outcome, and its results will likely change clinical practice.

PMID- 24923876
TI  - Gender-stereotyping and cognitive sex differences in mixed- and same-sex groups.
AB  - Sex differences in specific cognitive abilities are well documented, but the
      biological, psychological, and sociocultural interactions that may underlie these
      differences are largely unknown. We examined within a biopsychosocial approach
      how gender stereotypes affect cognitive sex differences when adult participants
      were tested in mixed- or same-sex groups. A total of 136 participants (70 women)
      were allocated to either mixed- or same-sex groups and completed a battery of sex
      sensitive cognitive tests (i.e., mental rotation, verbal fluency, perceptual
      speed) after gender stereotypes or gender-neutral stereotypes (control) were
      activated. To study the potential role of testosterone as a mediator for group
      sex composition and stereotype boost/threat effects, saliva samples were taken
      before the stereotype manipulation and after cognitive testing. The results
      showed the typical male and female advantages in mental rotation and verbal
      fluency, respectively. In general, men and women who were tested in mixed-sex
      groups and whose gender stereotypes had not been activated performed best.
      Moreover, a stereotype threat effect emerged in verbal fluency with reduced
      performance in gender stereotyped men but not women. Testosterone levels did not
      mediate the effects of group sex composition and stereotype threat nor did we
      find any relationship between testosterone and cognitive performance in men and
      women. Taken together, the findings suggest that an interaction of gender
      stereotyping and group sex composition affects the performance of men and women
      in sex-sensitive cognitive tasks. Mixed-sex settings can, in fact, increase
      cognitive performance as long as gender-stereotyping is prevented. 

PMID- 24923877
TI  - Feminized behavior and brain gene expression in a novel mouse model of
      Klinefelter Syndrome.
AB  - Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy in men and
      is characterized by the presence of an additional X chromosome (XXY). In some
      Klinefelter males, certain traits may be feminized or shifted from the male
      typical pattern towards a more female-typical one. Among them might be partner
      choice, one of the most sexually dimorphic traits in the animal kingdom. We
      investigated the extent of feminization in XXY male mice (XXYM) in partner
      preference and gene expression in the bed nucleus of the stria
      terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy
      model. We tested for partner preference using a three-chambered apparatus in
      which the test mouse was free to choose between stimulus animals of either sex.
      We found that partner preference in XXYM was feminized. These differences were
      likely due to interactions of the additional X chromosome with the Y. We also
      discovered genes that differed in expression in XXYM versus XYM. Some of these
      genes are feminized in their expression pattern. Lastly, we also identified genes
      that differed only between XXYM versus XYM and not XXM versus XYM. Genes that are
      both feminized and unique to XXYM versus XYM represent strong candidates for
      dissecting the molecular pathways responsible for phenotypes present in KS/XXYM
      but not XXM. In sum, our results demonstrated that investigating behavioral and
      molecular feminization in XXY males can provide crucial information about the
      pathophysiology of KS and may aid our understanding of sex differences in brain
      and behavior. 

PMID- 24923879
TI  - Open chromatin in plant genomes.
AB  - Sensitivity to DNase I digestion is an indicator of the accessibility and
      configuration of chromatin in eukaryotic genomes. Open chromatin exhibits high
      sensitivity to DNase I cleavage. DNase I hypersensitive sites (DHSs) in
      eukaryotic genomes can be identified through DNase I treatment followed by
      sequencing (DNase-seq). DHSs are most frequently associated with various cis
      regulatory DNA elements, including promoters, enhancers, and silencers in both
      animal and plant genomes. Genome-wide identification of DHSs provides an
      efficient method to interpret previously un-annotated regulatory DNA sequences.
      In this review, we provide an overview of the historical perspective of DHS
      research in eukaryotes. We summarize the main achievements of DHS research in
      model animal species and review the recent progress of DHS research in plants. We
      finally discuss possible future directions of using DHS as a tool in plant
      genomics research.

PMID- 24923878
TI  - Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac
      dysfunction in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Caffeic acid phenethyl ester (CAPE) has been shown to protect the
      heart against ischemia/reperfusion (I/R) injury by various mechanisms including
      its antioxidant effect. In this study, we evaluated the protective effects of a
      CAPE analog with more structural stability in plasma, caffeic acid phenethyl
      amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats.
      METHODS: Type 1 diabetes mellitus was induced in Sprague-Dawley rats by a single
      intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left
      anterior descending coronary artery was occluded for 45 minutes, followed by 2
      hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before
      reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl
      CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nomega-nitro-l
      arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in
      the reduction of the infarct size following CAPA-treatment. Finally, the
      cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic
      rats. RESULTS: Compared to the control group, CAPA administration (3 and 15
      mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA
      (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS
      inhibitor, (L-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial
      infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily)
      started 4 weeks after STZ-induction could effectively decrease the infarct size
      and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ
      induced diabetic animals. CONCLUSIONS: CAPA, which is structurally similar to
      CAPE, exerts cardioprotective activity in I/R injury through its antioxidant
      property and by preserving nitric oxide levels. On the other hand, chronic CAPA
      treatment could also ameliorate cardiac dysfunction in diabetic animals.

PMID- 24923880
TI  - Review of 268 lacrimal gland biopsies in an Australian cohort.
AB  - BACKGROUND: To review the distribution of pathology in lacrimal gland biopsies
      performed in an Australian cohort. DESIGN: Retrospective review. PARTICIPANTS:
      Two hundred sixty-eight lacrimal gland biopsies from 263 patients. METHODS:
      Pathology archives in South Australia and Victoria were searched for lacrimal
      gland biopsies performed between 1 January 1997 and 31 December 2012. Data
      retrieved included the year of biopsy, the histopathological diagnosis, patient
      age and gender. MAIN OUTCOME MEASURES: Distribution of pathology affecting the
      lacrimal gland; patient age and gender. RESULTS: The distribution of lacrimal
      gland pathology was: inflammations and vasculitides 50.0%, lymphomas 19.8%,
      lymphoid hyperplasias 12.3%, benign epithelial tumours 7.8% (all pleomorphic
      adenomas), malignant epithelial tumours 4.1%, dacryops 3.0% and miscellaneous
      3.0%. The mean age was 52 years, with lymphoma affecting the oldest patient group
      (64.6 years) and sarcoidosis the youngest (40.6 years). Of the patients with
      biopsy-confirmed dacryoadenitis, biopsy revealed a specific diagnosis in 34% of
      cases. Immunoglobulin G4-related disease was the most common 'specific'
      dacryoadenitis. Significantly more pleomorphic adenomas were diagnosed in the
      period 1997-2004 than the period 2005-2012 inclusive, but there were no other
      significant changes in the distribution of pathology over time. CONCLUSIONS: Two
      thirds of dacryoadenitis was 'non-specific', two thirds of epithelial tumours
      were pleomorphic adenomas and approximately two thirds of all lacrimal gland
      biopsies were accounted for by inflammations and lymphoid hyperplasias. The ratio
      of inflammations to neoplasias will be significantly influenced by the
      clinician's threshold for biopsying patients presenting with features of
      dacryoadenitis.

PMID- 24923881
TI  - Multifunctional properties of chicken embryonic prenatal mesenchymal stem cells-
      pluripotency, plasticity, and tumor suppression.
AB  - The chick embryo represents an accessible and economical in vivo model, which has
      long been used in developmental biology, gene expression analysis, and loss/gain
      of function experiments. In the present study, we assessed and characterized bone
      marrow derived mesenchymal stem cells from prenatal day 13 chicken embryos
      (chBMMSCs) and determined some novel properties. After assessing the mesenchymal
      stem cell (MSC) properties of these cells by the presence of their signature
      markers (CD 44, CD 73, CD 90, CD 105, and vimentin), we ascertained a very broad
      spectrum of multipotentiality as these MSCs not only differentiated into the
      classic tri-lineages of MSCs but also into ectodermal, endodermal, and mesodermal
      lineages such as neuron, hepatocyte, islet cell, and cardiac. In addition to wide
      plasticity, we detected the presence of several pluripotent markers such as Oct4,
      Sox2, and Nanog. This is the first study characterizing prenatal chBMMSCs and
      their ability to not only differentiate into mesenchymal lineages but also into
      all the germ cell layer lineages. Furthermore, our studies indicate that prenatal
      chBMMSCs derived from the chick provide an excellent model for multi-lineage
      development studies because of their broad plasticity and faithful reproduction
      of MSC traits as seen in the human. Here, we also present evidence for the first
      time that media derived from prenatal chBMMSC cultures have an anti-tumorigenic,
      anti-migratory, and pro-apoptotic effect on human tumors cells acting through the
      Wnt-beta-catenin pathway. These data confirm that chBMMSCs are enriched with
      factors in their secretome that are able to destroy tumor cells. This suggests a
      commonality of properties of MSCs across species between human and chicken. 

PMID- 24923882
TI  - Pro-chondrogenic effect of miR-221 and slug depletion in human MSCs.
AB  - In this study we have inhibited the expression of two negative regulators of
      chondrogenesis, Slug transcription factor (TF) and the small non-coding single
      stranded RNA microRNA-221 (miR-221), in human mesenchymal stem cells (MSCs). Our
      aim was test a new approach to guide the cells toward a chondrocyte - like
      phenotype, without the employment of differentiating agents, in the prospect of
      their clinical applications for cell-based cartilage tissue engineering. We have
      characterized these manipulated cells by gene expression analysis at the RNA and
      protein levels. We demonstrated that decreased miR-221 or Slug induced an
      increase of chondrogenic markers, including collagen type II (Col2A1), and the
      positive chondrogenic TFs Sox9 and TRPS1. Slug and TRPS1 are not direct targets
      of miR-221 since their expression was not affected by miR-221 content. Further,
      we showed by gene expression and Chromatin Immunoprecipitation analyses that i.
      miR-221 is positively regulated by Slug in hMSCs, where Slug and miR-221 high
      levels hamper cell differentiation, and ii. TRPS1 contributes to maintaining low
      levels of miR-221, both in hMSCs committed toward chondrogenesis by Slug
      depletion and in chondrocytes, where the low levels of miR-221 and Slug allow a
      chondrogenic phenotype.Taken together, our data may be relevant both to
      understand yet unknown miRNA - TF regulatory loops in cartilage biology and to
      establish new strategies based on a siRNA approach for cartilage tissue
      engineering. 

PMID- 24923883
TI  - Lipoxin A4 suppresses the development of endometriosis in an ALX receptor
      dependent manner via the p38 MAPK pathway.
AB  - BACKGROUND AND PURPOSE: Lipoxins can function as endogenous 'breaking signals' in
      inflammation and play important roles in the progression of endometriosis. In
      this study, we further investigated the molecular mechanism by which lipoxin A4
      (LXA4 ) suppresses the development of endometriosis. EXPERIMENTAL APPROACH:
      Primary endometriotic stromal cells (ESCs) were treated with IL-1beta, or pre
      incubated with LXA4 before incubation with IL-1beta. The LXA4 receptor (ALX
      receptor) antagonist Boc-2 and gene-silencing approaches were used to study the
      involvement of the ALX receptor in anti-inflammatory signalling responses in
      ESCs. An animal model of endometriosis was induced in BALB/c mice by i.p.
      injection of an endometrium-rich fragment. KEY RESULTS: Decreased levels of LXA4
      and 15-LOX-2 expression but increased expression of AXL receptors were observed
      in endometriotic tissues. LXA4 inhibited the release of inflammatory factors and
      phosphorylation of p38 MAPK in IL-1beta-induced ESCs, an effect mediated by ALX
      receptors. LXA4 inhibited the proliferation of ESCs, as indicated by reduced DNA
      replication, caused G0 /G1 phase cell cycle arrest and down-regulated the
      expression of proliferating cell nuclear antigen in ESCs. LXA4 also attenuated
      the invasive activity of ESCs mainly by suppressing the expression and activity
      of MMP-9. In vivo, we further confirmed that LXA4 could inhibit the progression
      of endometriosis by acting as an anti-inflammatory. CONCLUSIONS AND IMPLICATIONS:
      LXA4 exerted anti-inflammatory, anti-proliferative and anti-invasive effects on
      endometriosis through a mechanism that involved down-regulating the activities of
      p38 MAPK, which was mediated by ALX receptors.

PMID- 24923885
TI  - A self-categorization theory perspective on adolescent boys' sexual bullying of
      girls.
AB  - This preliminary study applied Self-Categorization Theory (SCT) to the sexual
      bullying of high school girls by boys. Seventy-five Year 9 boys responded to
      vignettes portraying sexual bullying in which gender was a more or a less salient
      feature of the social context described. As predicted, boys were more likely to
      engage in sexual bullying when gender was more salient. Masculine sex role was
      not correlated with engagement in sexual bullying. Controlling for social
      desirability, pro-bullying attitude was predictive of such engagement, but only
      when the social context rendered gender less salient. This suggests the power of
      the perceived social context for determining which individual characteristics
      will gain expression. It is concluded that SCT is a promising avenue for
      advancing understanding of bullying, a field of research that has previously
      largely lacked a theoretical focus. 

PMID- 24923884
TI  - Comparative genomic analysis of Mycobacterium tuberculosis clinical isolates.
AB  - BACKGROUND: Due to excessive antibiotic use, drug-resistant Mycobacterium
      tuberculosis has become a serious public health threat and a major obstacle to
      disease control in many countries. To better understand the evolution of drug
      resistant M. tuberculosis strains, we performed whole genome sequencing for 7 M.
      tuberculosis clinical isolates with different antibiotic resistance profiles and
      conducted comparative genomic analysis of gene variations among them. RESULTS: We
      observed that all 7 M. tuberculosis clinical isolates with different levels of
      drug resistance harbored similar numbers of SNPs, ranging from 1409-1464. The
      numbers of insertion/deletions (Indels) identified in the 7 isolates were also
      similar, ranging from 56 to 101. A total of 39 types of mutations were identified
      in drug resistance-associated loci, including 14 previously reported ones and 25
      newly identified ones. Sixteen of the identified large Indels spanned PE-PPE-PGRS
      genes, which represents a major source of antigenic variability. Aside from SNPs
      and Indels, a CRISPR locus with varied spacers was observed in all 7 clinical
      isolates, suggesting that they might play an important role in plasticity of the
      M. tuberculosis genome. The nucleotide diversity (L value) and selection
      intensity (dN/dS value) of the whole genome sequences of the 7 isolates were
      similar. The dN/dS values were less than 1 for all 7 isolates (range from
      0.608885 to 0.637365), supporting the notion that M. tuberculosis genomes undergo
      purifying selection. The L values and dN/dS values were comparable between drug
      susceptible and drug-resistant strains. CONCLUSIONS: In this study, we show that
      clinical M. tuberculosis isolates exhibit distinct variations in terms of the
      distribution of SNP, Indels, CRISPR-cas locus, as well as the nucleotide
      diversity and selection intensity, but there are no generalizable differences
      between drug-susceptible and drug-resistant isolates on the genomic scale. Our
      study provides evidence strengthening the notion that the evolution of drug
      resistance among clinical M. tuberculosis isolates is clearly a complex and
      diversified process.

PMID- 24923886
TI  - Intimate partner violence, coercive control, and child adjustment problems.
AB  - Coercive control is a relationship dynamic that is theorized to be key for
      understanding physical intimate partner violence (IPV). This research examines
      how coercive control in the context of physical IPV may influence child
      adjustment. Participants were 107 mothers and their children, aged 7 to 10 years.
      In each family, mothers reported the occurrence of at least one act of physical
      IPV in the past 6 months. Mothers reported on physical IPV and coercive control,
      and mothers and children reported on children's externalizing and internalizing
      problems. Coercive control in the context of physical IPV related positively with
      both mothers' and children's reports of child externalizing and internalizing
      problems, after accounting for the frequency of physical IPV, psychological
      abuse, and mothers' education. This research suggests that couple relationship
      dynamics underlying physical IPV are potentially important for understanding how
      physical IPV leads to child adjustment problems. 

PMID- 24923887
TI  - Spanking of young children: do immigrant and U.S.-born Hispanic parents differ?
AB  - Building on prior research showing fewer parenting risk behaviors and lower
      levels of harsh punishment among less acculturated Hispanic parents, we tested
      the hypothesis that foreign-born (FB; immigrant) Hispanic parents use less
      spanking toward children at 3 years and 5 years of age than U.S.-born Hispanic
      parents. We also examined whether other indicators of acculturation-endorsement
      of traditional gender norms and religiosity-showed any direct or indirect effects
      in explaining the hypothesized association. Path model analyses were conducted
      with a sample of Hispanic mothers (n = 1,089) and fathers (n = 650). Cross
      sectional and time lagged path models controlling for a wide range of
      psychosocial and demographic confounds indicated that, when compared with U.S.
      born Hispanic parents, FB Hispanic mothers and fathers used less spanking toward
      their young children. In cross-sectional analysis only, mothers' greater
      endorsement of traditional gender norms had small protective effects on spanking.
      Although fathers' endorsement of traditional gender norms was not a significant
      direct predictor of spanking, there was a significant indirect effect of nativity
      status on spanking mediated by endorsement of traditional gender norms.
      Religiosity showed no relation to spanking for either mothers or fathers.
      Immigrant status may be an important protective factor that is associated with
      lower levels of parenting aggression among Hispanic mothers and fathers living in
      the United States. 

PMID- 24923888
TI  - Social desirability and partner agreement of men's reporting of intimate partner
      violence in substance abuse treatment settings.
AB  - Estimates indicate that intimate partner violence (IPV) occurs in approximately
      30% of relationships and up to 85% of the relationships of men in substance abuse
      treatment. However, partners consistently display poor agreement in reporting the
      presence of IPV. Social desirability is frequently offered as the primary reason
      for under-reporting of IPV by perpetrators. The goal of the current study was to
      explicitly test the social desirability hypothesis using both partners' reports
      of negotiation, psychological aggression, physical aggression, sexual aggression,
      and injuries in a substance abuse treatment sample. A total of 54 males and their
      female partners were recruited from a residential adult substance use treatment
      facility. Consistent with prior literature, partners displayed poor agreement
      about the presence of different types of IPV. The male partner's social
      desirability was not associated with his reporting of male-to-female physical
      aggression, psychological aggression, or injuries. Men who engaged in higher
      levels of self-deceptive enhancement and lower levels of impression management
      were more likely to under-report male-to-female sexual coercion. Overall, the
      findings question the generalized importance of social desirability in IPV
      reporting in substance abuse treatment populations. 

PMID- 24923889
TI  - Beyond Clery Act statistics: a closer look at college victimization based on self
      report data.
AB  - This study examined the relationships among victimization, demographic
      characteristics, and activity choices in a cross-sectional sample of 479
      undergraduate students. In the sample, 74% was female and 65% was Caucasian, with
      an even distribution of ages ranging from 18 to 22+ years; all participants
      completed an online survey. Using survey feedback, the study team performed
      multivariate regression analysis and reported quantity and type of victimization
      experiences in relation to factors that may contribute to identifying groups at
      risk for experiencing violence. Findings suggest that gender, grade point
      average, and membership in student organizations or Greek-letter organizations
      influence students' potential for different types of victimization. Furthermore,
      alcohol use and household income did not have a statistically significant
      relationship with any victimization types. Finally, rates reported indicate
      student underreporting and illustrate difficulty implementing the Clery Act.
      Policy recommendations, future research, and limitations are discussed. With
      accurate victimization data, resources and services may be more efficiently
      allocated to meet the needs of students at greater risk for victimization. 

PMID- 24923890
TI  - Effect of face-to-face interview versus computer-assisted self-interview on
      disclosure of intimate partner violence among African American women in WIC
      clinics.
AB  - African American women in the United States report intimate partner violence
      (IPV) more often than the general population of women. Overall, women underreport
      IPV because of shame, embarrassment, fear of retribution, or low expectation of
      legal support. African American women may be especially unlikely to report IPV
      because of poverty, low social support, and past experiences of discrimination.
      The purpose of this article is to determine the context in which low-income
      African American women disclose IPV. Consenting African American women receiving
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      services in WIC clinics were randomized to complete an IPV screening (Revised
      Conflict Tactics Scales-Short Form) via computer-assisted self-interview (CASI)
      or face-to-face interview (FTFI). Women (n = 368) reported high rates of lifetime
      and prior-year verbal (48%, 34%), physical (12%, 7%), sexual (10%, 7%), and any
      (49%, 36%) IPV, as well as IPV-related injury (13%, 7%). Mode of screening, but
      not interviewer race, affected disclosure. Women screened via FTFI reported
      significantly more lifetime and prior-year negotiation (adjusted odds ratio [aOR]
      = 10.54, 3.97) and more prior-year verbal (aOR = 2.10), sexual (aOR = 4.31), and
      any (aOR = 2.02) IPV than CASI-screened women. African American women in a WIC
      setting disclosed IPV more often in face-to-face than computer screening, and
      race-matching of client and interviewer did not affect disclosure. Findings
      highlight the potential value of face-to-face screening to identify women at risk
      of IPV. Programs should weigh the costs and benefits of training staff versus
      using computer-based technologies to screen for IPV in WIC settings. 

PMID- 24923891
TI  - Physical dating violence, sexual violence, and unwanted pursuit victimization: a
      comparison of incidence rates among sexual-minority and heterosexual college
      students.
AB  - The purpose of this study was to estimate the 6-month incidence rates of sexual
      assault, physical dating violence (DV), and unwanted pursuit (e.g., stalking)
      victimization among sexual-minority (i.e., individuals with any same-sex sexual
      experiences) college students with comparison data from non-sexual-minority
      (i.e., individuals with only heterosexual sexual experiences) college students.
      Participants (N = 6,030) were primarily Caucasian (92.7%) and non-sexual-minority
      (82.3%). Compared with non-sexual-minority students (N-SMS; n = 4,961), sexual
      minority students (SMS; n = 1,069) reported significantly higher 6-month
      incidence rates of physical DV (SMS: 30.3%; N-SMS: 18.5%), sexual assault (SMS:
      24.3%; N-SMS: 11.0%), and unwanted pursuit (SMS: 53.1%; N-SMS: 36.0%)
      victimization. We also explored the moderating role of gender and found that
      female SMS reported significantly higher rates of physical DV than female N-SMS,
      whereas male SMS and male N-SMS reported similar rates of physical DV. Gender did
      not moderate the relationship between sexual-minority status and victimization
      experiences for either unwanted pursuit or sexual victimization. These findings
      underscore the alarmingly high rates of interpersonal victimization among SMS and
      the critical need for research to better understand the explanatory factors that
      place SMS at increased risk for interpersonal victimization. 

PMID- 24923892
TI  - Sexual victimization history, depression, and task physiology as predictors of
      sexual revictimization: results from a 6-month prospective pilot study.
AB  - The current study examined depression and physiological reactivity to a sexual
      threat task as longitudinal predictors of sexual revictimization in women with
      sexual victimization histories. The sample included 14 young adult women (M(age)
      = 19.15) who reported child sexual abuse. Heart rate and root mean square of the
      successive differences were measured at baseline and during the presentation of
      sexual victimization-related words during an Emotional Stroop task. Results
      indicated that women who reported a greater history of childhood sexual abuse and
      adult sexual victimization were at increased risk for sexual revictimization 6
      months after initial data collection. Furthermore, even after accounting for
      their childhood and adult sexual victimization histories and depression symptoms,
      women who exhibited reduced, or blunted, physiological activity during the sexual
      victimization stimuli of the Stroop task were more likely to report sexual
      revictimization during the 6-month follow-up. The findings suggest that sexual
      victimization survivors may benefit from interventions that address physiological
      blunting and the recognition of sexual threat cues in their environment.

PMID- 24923893
TI  - Domestic violence against women in Kosovo: a qualitative study of women's
      experiences.
AB  - Research on gender-based violence describes domestic violence by male partners as
      a major public health issue and serious human rights violation. Many studies have
      been conducted in Kosovo to understand the factors that contribute to violence
      against women. The present study aims to examine the experiences of battered
      women and their understanding of the violence from an ecological framework, by
      asking questions regarding personal, situational, and socio-cultural factors. The
      study is qualitative, consisting of 50 in-depth interviews with victims of
      domestic violence, and uses a grounded theory approach to identify main themes of
      the women's experiences. Findings from the study suggest that poverty, a
      patriarchal culture, strictly defined gender roles, and lack of programs for
      reintegrating victims subordinate women and leave them susceptible to domestic
      violence. 

PMID- 24923894
TI  - Judgments of social awkwardness from brief exposure to children with and without
      high-functioning autism.
AB  - We form first impressions of many traits based on very short interactions. This
      study examines whether typical adults judge children with high-functioning autism
      to be more socially awkward than their typically developing peers based on very
      brief exposure to still images, audio-visual, video-only, or audio-only
      information. We used video and audio recordings of children with and without high
      functioning autism captured during a story-retelling task. Typically developing
      adults were presented with 1 s and 3 s clips of these children, as well as still
      images, and asked to judge whether the person in the clip was socially awkward.
      Our findings show that participants who are naive to diagnostic differences
      between the children in the clips judged children with high-functioning autism to
      be socially awkward at a significantly higher rate than their typically
      developing peers. These results remain consistent for exposures as short as 1 s
      to visual and/or auditory information, as well as for still images. These data
      suggest that typical adults use subtle nonverbal and non-linguistic cues produced
      by children with high-functioning autism to form rapid judgments of social
      awkwardness with the potential for significant repercussions in social
      interactions. 

PMID- 24923895
TI  - Cognitive-behavioral therapy for anxiety in youth with an autism spectrum
      disorder: A follow-up study.
AB  - Cognitive-behavioral therapy for anxiety in youth with an autism spectrum
      disorder appears efficacious; however, maintenance of treatment gains has not yet
      been studied. Using a sample of 32 youth who had benefited at least minimally
      from a past trial of cognitive-behavioral therapy for anxiety in autism spectrum
      disorder, this study assessed anxiety symptoms in youth 10-26 months following
      treatment completion. Compared to baseline, follow-up scores were associated with
      large effects for treatment. Relative to post-treatment, a small effect for
      return in symptoms was present and significantly fewer individuals were rated as
      responders at follow-up. Future studies should investigate factors associated
      with poor treatment maintenance and modifications or additions to treatment that
      may help maintain treatment gains. 

PMID- 24923896
TI  - Limitations in social anticipation are independent of imaginative and Theory of
      Mind abilities in children with autism but not in typically developing children.
AB  - Anticipating future interactions is characteristic of our everyday social
      experiences, yet has received limited empirical attention. Little is known about
      how children with autism spectrum disorder, known for their limitations in social
      interactive skills, engage in social anticipation. We asked children with autism
      spectrum disorder and their typically developing counterparts to consider an
      interaction with another person in the near future. Our results suggest that
      children with autism spectrum disorder and typically developing children
      performed similarly when anticipating the age, gender, and possible questions of
      another person, but children with autism spectrum disorder struggled more to
      anticipate what they would say in response to an anticipated interaction.
      Furthermore, such responses were robustly associated with imaginative capacities
      in typically developing children but not children with autism spectrum disorder.
      Our findings suggest that the cognitive mechanisms of social anticipation may
      differ between these groups. 

PMID- 24923897
TI  - Thymoma with loss of keratin expression (and giant cells): a potential diagnostic
      pitfall.
AB  - Due to its profound therapeutic consequences, the distinction between thymoma and
      T-lymphoblastic lymphoma in needle biopsies is one of the most challenging in
      mediastinal pathology. One essential diagnostic criterion favouring thymoma is
      the demonstration of increased numbers of keratin-positive epithelial cells by
      immunohistochemistry. Loss of keratin expression in neoplastic epithelial cells
      could lead to detrimental misdiagnoses. We here describe a series of 14 thymic
      epithelial tumours (11 type B2 and B3 thymomas, 3 thymic carcinomas) with loss of
      expression of one or more keratins. Cases were analysed for expression of various
      keratins and desmosomal proteins by immunohistochemistry and immunofluorescence
      and compared with 45 unselected type B thymomas and 24 thymic carcinomas arranged
      in a multitissue histological array. All 14 cases showed highly reduced
      expression of at least one keratin, three cases were completely negative for all
      keratins studied. Of the 14 cases, 13 showed strong nuclear expression of p63.
      Expression of desmosomal proteins was preserved, suggesting intact cell contact
      structures. Loss of expression of broad-spectrum-keratins and K19 was observed in
      3 and 5 % of unselected thymomas and in 30 and 60 % of thymic carcinomas. A
      proportion of keratin-depleted thymomas contained giant cells, reminiscent of
      thymic nurse cells. Loss of keratin expression in type B2 and B3 thymomas is an
      important diagnostic pitfall in the differential diagnosis with T-lymphoblastic
      lymphoma and can be expected in 5 % of cases. A panel of epithelial markers
      including p63 is warranted to ensure correct diagnosis of keratin-negative
      mediastinal tumours.

PMID- 24923898
TI  - Non-functioning adrenal incidentalomas are associated with higher hypertension
      prevalence and higher risk of atherosclerosis.
AB  - INTRODUCTION: Adrenal incidentalomas (AIs) have been associated with an increased
      incidence of several cardiovascular risk factors. The aim of this study was to
      investigate plasma adiponectin, leptin, resistin, homocysteine, high sensitive C
      reactive protein levels, and carotid intima media thickness (CIMT) in patients
      with non-functioning AI (NFAI). MATERIALS AND METHODS: This study included data
      from 28 patients with NFAI (Group 1) and 41 controls (Group 2). Of the patients,
      50 were female and 19 were male, and the mean age was 46.7 (range 37-65) years.
      RESULTS: There were no significant differences between Group 1 and 2 in terms of
      age, sex, or BMI. Hypertension prevalence was significantly higher in the NFAI
      group than in the control group (p = 0.01). Both groups had similar lipid, blood
      glucose, homocysteine, uric acid, high-sensitivity CRP levels. Adiponectin,
      leptin, and resistin levels were similar in both groups. CIMTs were significantly
      higher in the NFAI group. CONCLUSION: There is increasing evidence that several
      cardiometabolic risk factors occur with higher prevalence in non-functioning
      adrenal incidentaloma patients compared to age-matched healthy subjects. In our
      study, hypertension prevalence and CIMT were higher in the NFAI group. Serum
      adipokine levels were similar for both groups.

PMID- 24923899
TI  - The gonadal function in obese adolescents: review.
AB  - This review deals with the relationship between obesity in male adolescents and
      gonadal function. The article is structured in two main paragraphs; the first one
      is about population studies that have assessed puberty timing and its mode of
      onset in relation with body weight to evaluate if and how the latter can
      influence the gonadal function in this phase of life. These studies analyze
      issues such as increased BMI and early onset of male puberty, gender differences,
      secular trend toward early onset of puberty in males, effects of a different body
      composition on male puberty and consequences of a different stage of childhood
      obesity on the onset of male puberty. The second paragraph examines the possible
      mechanisms through which, obesity may alter the timing of puberty in young males,
      including the role of SHBG, leptin, insulin resistance, ghrelin, GH-IGF-1 axis,
      AR polymorphisms, primary testicular dysfunction, retinol binding protein 4 (RBP
      4) and liver function abnormalities. However, despite the numerous studies in the
      literature, the etiology of gonadal disfunction in obese adolescents on puberty
      remains uncertain. 

PMID- 24923900
TI  - Vitamin D levels in a paediatric population of normal weight and obese subjects.
AB  - BACKGROUND: Vitamin D exerts pleiotropic effects and few studies are available in
      the Italian population. AIM: Aim of our study was to evaluate vitamin D status in
      children living in Northern Italy. METHODS: We studied vitamin D levels in a
      population of 113 normal weight (NW) and 444 obese (OB) children, prepubertal and
      pubertal. We considered vitamin D levels >20 ng/ml as normal, but also measured
      percentage of children with vitamin D levels higher than a cutoff of 30 ng/ml.
      RESULTS: 68.2 % of NW children showed normal levels of vitamin D, while 31.8 %
      showed a clear vitamin D deficiency. Only 28.3 % showed vitamin D levels higher
      than 30 ng/ml. Obese children showed 55.6 % of subjects with normal levels of
      vitamin D and 44.4 % of subjects a status of vitamin D deficiency. Only the 18.9
      % showed vitamin D levels higher than 30 ng/ml. Mean vitamin D levels in NW
      children (27.3 +/- 1.2 ng/ml) were higher than in OB children (21.8 +/- 0.6
      ng/ml). No differences have been found between prepubertal and pubertal children
      in terms of vitamin D levels. CONCLUSIONS: Our paediatric population demonstrates
      a low percentage of vitamin D sufficiency. In particular, obese children show
      only 19 % of subjects with normal levels while almost half of this population
      shows a clear deficiency. Further studies are needed to support these results and
      to evaluate the possible metabolic consequences.

PMID- 24923901
TI  - Site-specific changes in cytokine response to septic dose of lipopolysaccharide
      in ovariectomized female rats.
AB  - PURPOSE: The immune response is altered according to hormonal and metabolic
      status. Obesity increases the inflammatory and fever response, whereas loss of
      gonadal steroid decreases behavioral response to immune stress. However, the
      immune systems of ovariectomized animals exhibiting obesity and gonadal steroid
      deficiency, particularly under septic conditions, have not been fully examined.
      In the present study, we evaluated the ovariectomy-induced changes of central and
      peripheral immune responses to life-threatening septic stimulus. METHODS AND
      RESULTS: Ovariectomized rats showed heavier body weight and lighter uterine
      weight when compared with gonadally intact rats. Fever response to septic dose of
      lipopolysaccharide (LPS) in ovariectomized rats was less evident when compared
      with that in gonadally intact rats. In addition, under LPS-injected septic
      conditions, hypothalamic gene levels of Interleukin-1beta (IL-1beta), Interleukin
      6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and serum protein levels of
      IL-1beta and TNF-alpha in ovariectomized rats were lower than those in gonadally
      intact rats. On the other hand, IL-6 levels in visceral fat under septic
      conditions were higher in ovariectomized rats than in gonadally intact rats.
      CONCLUSIONS: These findings indicate that ovariectomy-induced site-specific
      changes in cytokine response under septic conditions. As hypothalamic, but not
      peripheral, pro-inflammatory cytokines are directly involved in the fever
      response, the attenuation of fever response observed in ovariectomized rats may
      be caused by a reduction in central cytokine responses.

PMID- 24923902
TI  - Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and
      neck cancer.
AB  - Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for
      various cancers, particularly for recurrent cancers that no longer respond to
      conventional anticancer therapies. PDT has been under development for decades,
      but light-associated toxicity limits its clinical applications. To reduce the
      toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that
      combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and
      iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a
      fibronectin-mimetic peptide (Fmp), which binds integrin beta1. Then the PDT drug
      Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate
      Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp
      IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than
      nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of
      HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower
      dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs
      demonstrated significantly greater inhibition of tumor growth than nontargeted IO
      Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs
      can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs
      have great potential to serve as both a magnetic resonance imaging (MRI) agent
      and PDT drug in the clinic.

PMID- 24923904
TI  - Volatile sulphur compound levels and related factors in patients with chronic
      renal failure.
AB  - AIMS: To analyse specific volatile sulphur compound(VSC) levels in a group of
      chronic renal failure (CRF) patients and determine the relationship between these
      VSC levels and organoleptic measurements, blood urea nitrogen (BUN) levels,
      dental and periodontal conditions, salivary flow rate, and tongue coating scores.
      MATERIALS AND METHODS: One examiner performed organoleptic and VSC measurements
      on fifty patients with CRF before and after haemodialysis (HD) and controls. DMFT
      and CPITN indexes, tongue coating scores, salivary flow rates were measured.
      Comparisons were performed using the Mann-Whitney U, Wilcoxon signed-ranks, and
      chi-square tests. Spearman correlation coefficient was used to analyse
      correlations. RESULTS: Before HD, the mean dimethyl sulphide level was 1.04 +/-
      1.20 in the CRF patients and 0.51 +/- 0.65 in controls, with a significant
      difference. The mean hydrogen sulphide, methyl mercaptan and dimethyl sulphide
      levels in CRF patients were 1.47 +/- 3.04, 1.03 +/- 1.85, and 1.04 +/- 1.20,
      respectively, before HD; and 0.53 +/- 1.65, 0.48 +/- 1.27, and 0.56 +/- 0.85,
      respectively, after HD; with the differences being significant. Methyl mercaptan
      levels increased with an increase in HD duration. Tongue coating and organoleptic
      measurements were significantly correlated with methyl mercaptan. CONCLUSIONS:
      Dimethyl sulphide is the main VSC in extraoral blood-borne halitosis; but methyl
      mercaptan may also contribute to this type of halitosis. A decreased salivary
      flow rate and an increased pH of the biofilm matrix may be a significant
      parameter for VSC levels in CRF patients.

PMID- 24923906
TI  - Macrophagic myofasciitis and vaccination: consequence or coincidence?
AB  - Macrophagic myofasciitis (MMF) characterized by specific muscle lesions assessing
      long-term persistence of aluminum hydroxide within macrophages at the site of
      previous immunization has been reported with increasing frequency in the past 10
      years. We describe clinical and laboratory findings in patients with MMF. We did
      a retrospective analysis of 16 cases observed in our Neuropathology Laboratory,
      between January 2000 and July 2013. The mean age of the 16 patients was 48.8 +/-
      18.0 years; 80.0 % were female. Chronic fatigue syndrome was found in 8 of 16
      patients. Half of the patients had elevated creatinine kinase levels, and 25.0 %
      had a myopathic electromyogram. Thirteen patients received intramuscular
      administration of aluminum-containing vaccine prior to the onset of symptoms. MMF
      may mirror a distinctive pattern of an inflammatory myopathy. The vaccines
      containing this adjuvant may trigger MMF in some patients.

PMID- 24923907
TI  - Empathy in intimate relationships: the role of positive illusions.
AB  - Previous studies have shown empathy to be an important aspect of a high quality
      intimate relationship. Likewise, positive illusions about a partner's
      characteristics have been shown to contribute to relationship quality. The
      present study connects these issues by examining the degree to which individuals
      hold positive illusions about a partner's level of empathy, and the extent to
      which these positive illusions are related to relationship quality and adjustment
      in a sample of 55 couples. Results showed that positive illusions concerning a
      partner's level of empathy were only held by women. In addition, people's
      evaluation of relationship quality and adjustment was consistently related to
      both their own and their partner's positive empathy illusions. Finally, an
      interaction effect was found between participant sex and the partner effect of
      positive empathy illusions: the illusions held by the partner (only for men) were
      related to relationship quality. Results and implications for theory and
      relationship counseling are discussed. 

PMID- 24923908
TI  - Cross-cultural equivalence of the patient- and parent-reported quality of life in
      short stature youth (QoLISSY) questionnaire.
AB  - BACKGROUND: Testing cross-cultural equivalence of patient-reported outcomes
      requires sufficiently large samples per country, which is difficult to achieve in
      rare endocrine paediatric conditions. We describe a novel approach to cross
      cultural testing of the Quality of Life in Short Stature Youth (QoLISSY)
      questionnaire in five countries by sequentially taking one country out (TOCO)
      from the total sample and iteratively comparing the resulting psychometric
      performance. METHODS: Development of the QoLISSY proceeded from focus group
      discussions through pilot testing to field testing in 268 short-statured patients
      and their parents. To explore cross-cultural equivalence, the iterative TOCO
      technique was used to examine and compare the validity, reliability, and
      convergence of patient and parent responses on QoLISSY in the field test dataset,
      and to predict QoLISSY scores from clinical, socio-demographic and psychosocial
      variables. RESULTS: Validity and reliability indicators were satisfactory for
      each sample after iteratively omitting one country. Comparisons with the total
      sample revealed cross-cultural equivalence in internal consistency and construct
      validity for patients and parents, high inter-rater agreement and a substantial
      proportion of QoLISSY variance explained by predictors. CONCLUSION: The TOCO
      technique is a powerful method to overcome problems of country-specific testing
      of patient-reported outcome instruments. It provides an empirical support to
      QoLISSY's cross-cultural equivalence and is recommended for future research.

PMID- 24923909
TI  - Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an
      Alzheimer's [corrected] disease model.
AB  - Amyloid plaques and tau tangles are common pathological hallmarks for Alzheimer's
      disease (AD); however, reducing Abeta production failed to relieve the symptoms
      of AD patients. Here we report a high GABA (gamma-aminobutyric acid) content in
      reactive astrocytes in the dentate gyrus (DG) of a mouse model for AD (5xFAD)
      that results in increased tonic inhibition and memory deficit. We also confirm in
      human AD patient brains that dentate astrocytes have a high GABA content,
      suggesting that high astrocytic GABA level may be a novel biomarker and a
      potential diagnostic tool for AD. The excessive GABA in 5xFAD astrocytes is
      released through an astrocyte-specific GABA transporter GAT3/4, and significantly
      enhances tonic GABA inhibition in dentate granule cells. Importantly, reducing
      tonic inhibition in 5xFAD mice rescues the impairment of long-term potentiation
      (LTP) and memory deficit. Thus, reducing tonic GABA inhibition in the DG may lead
      to a novel therapy for AD. 

PMID- 24923911
TI  - Comment on Ma XL et al.: prognostic role of circulating tumor cells and
      disseminated tumor cells in patients with prostate cancer: a systematic review
      and meta-analysis.

PMID- 24923910
TI  - Direct sensing of 5-methylcytosine by polymerase chain reaction.
AB  - The epigenetic control of genes by the methylation of cytosine resulting in 5
      methylcytosine (5mC) has fundamental implications for human development and
      disease. Analysis of alterations in DNA methylation patterns is an emerging tool
      for cancer diagnostics and prognostics. Here we report that two thermostable DNA
      polymerases, namely the DNA polymerase KlenTaq derived from Thermus aquaticus and
      the KOD DNA polymerase from Thermococcus kodakaraensis, are able to extend 3'
      mismatched primer strands more efficiently from 5 mC than from unmethylated C.
      This feature was advanced by generating a DNA polymerase mutant with further
      improved 5mC/C discrimination properties and its successful application in a
      novel methylation-specific PCR approach directly from untreated human genomic
      DNA. 

PMID- 24923913
TI  - I want to complain.

PMID- 24923912
TI  - Identification of a novel protein complex containing ASIC1a and GABAA receptors
      and their interregulation.
AB  - Acid-sensing ion channels (ASICs) belong to the family of the epithelial sodium
      channel/degenerin (ENaC/DEG) and are activated by extracellular protons. They are
      widely distributed within both the central and peripheral nervous systems. ASICs
      were modified by the activation of gamma-aminobutyric acid receptors (GABAA), a
      ligand-gated chloride channels, in hippocampal neurons. In contrast, the activity
      of GABAA receptors were also modulated by extracellular pH. However so far, the
      mechanisms underlying this intermodulation remain obscure. We hypothesized that
      these two receptors-GABAA receptors and ASICs channels might form a novel protein
      complex and functionally interact with each other. In the study reported here, we
      found that ASICs were modified by the activation of GABAA receptors either in
      HEK293 cells following transient co-transfection of GABAA and ASIC1a or in
      primary cultured dorsal root ganglia (DRG) neurons. Conversely, activation of
      ASIC1a also modifies the GABAA receptor-channel kinetics. Immunoassays showed
      that both GABAA and ASIC1a proteins were co-immunoprecipitated mutually either in
      HEK293 cells co-transfected with GABAA and ASIC1a or in primary cultured DRG
      neurons. Our results indicate that putative GABAA and ASIC1a channels
      functionally interact with each other, possibly via an inter-molecular
      association by forming a novel protein complex. 

PMID- 24923914
TI  - Dental radiography: gold thread therapy.

PMID- 24923915
TI  - Evidence-based dentistry: more than just P values.

PMID- 24923916
TI  - Dental instruments: operating otoscope.

PMID- 24923917
TI  - Risk to fish-eating vertebrates.

PMID- 24923918
TI  - Pain relief clinic celebrates 15 years.

PMID- 24923920
TI  - Nation unites to improve oral health.

PMID- 24923919
TI  - Myth-busting: donkey dentistry and other stories.

PMID- 24923923
TI  - A physiotherapist's life.

PMID- 24923927
TI  - Dental stem cells may assist stroke patients.

PMID- 24923929
TI  - Largest study of its kind connects tooth loss with heart disease.

PMID- 24923932
TI  - "Delayed" cocaine poisoning.

PMID- 24923933
TI  - Denture identification marking should be standard practice.
AB  - The focus of this opinion article is to revisit whether denture identification
      marking should be routine and standard practice at manufacture in the United
      Kingdom. The benefits of denture identification marking are evident in the
      literature particularly for those who are in residential care or who will have to
      seek care due to dementia or physical frailty; however, within the UK it is not
      normally practised. Many patients would appear to be unaware of denture marking,
      but present positive attitudes towards it. Results of a survey of UK dental
      laboratories would indicate that the vast majority of them offer an inclusion
      denture marking service with a mean cost of L5 per denture. Is the lack of
      denture marking in the UK due to dental professionals having differences in
      opinion, lack of education of professionals in training or financial
      disincentives? 

PMID- 24923934
TI  - Minimal intervention dentistry: part 8. Biotherapies for the dental pulp.
AB  - The development of new therapies, the biotherapies, can now be envisioned in
      dentistry thanks to the important development of research in the stem cell and
      biomaterial fields. Indeed, the recent discovery of stem cells in different
      tissues of the body, and in particular in the dental pulp, should allow the
      development of new therapeutic approaches for pulpo-dentinal lesions. In case of
      moderate pulp injury, the stimulation by biomolecules of pulp stem cells located
      in the remaining pulp is the approach to be considered. In case of more severe
      lesions requiring a total removal of pulp tissues, a cell therapy could be
      considered. The objective of this article is to present these innovative
      therapeutic approaches for the future of dentistry. 

PMID- 24923936
TI  - Minimal intervention dentistry in the management of the paediatric patient.
AB  - Minimal intervention dentistry (MID) is a philosophy of care that aims to
      conserve tooth tissues throughout a persons' life. This paper aims to review the
      literature on topics that are related to MID approaches for the management of
      dental caries and that can be applicable to the paediatric patient. Tools for
      caries diagnosis and early lesion detection are presented and discussed. More
      conservative and less invasive techniques for managing enamel and dentine carious
      lesions in primary and permanent teeth are compared to the traditional
      treatments. The traditional treatments are centred on the disease and on
      restoring its sequels, and have been shown to be insufficiently effective in
      controlling caries disease over time. In contrast, the MID philosophy has created
      potentially very suitable options for treating children that are considered more
      child-friendly, less anxiety provoking, preserve more tooth tissues and are
      equally good as the traditional treatments. 

PMID- 24923937
TI  - General medicine and surgery for dental practitioners: part 1. History taking and
      examination of the clothed patient.
AB  - All dental practitioners must be proficient at taking a medical history,
      examining a clothed patient and recognising relevant clinical signs. The general
      examination of a patient should take into account findings from the history. This
      paper does not attempt to address the detailed oral and dental examination
      carried out by dental practitioners but focuses on the holistic patient
      assessment - essential for safe patient management. 

PMID- 24923938
TI  - General medicine and surgery for dental practitioners: part 2. Medical
      emergencies in dental practice: the drug box, equipment and basic principles of
      management.
AB  - Dental practitioners need knowledge of the diagnosis and management of medical
      emergencies. This paper deals with the general aspects of emergency treatment
      including basic management principles which are applicable to all emergencies.
      The next paper in this series, part 3, deals with more specific aspects of
      medical emergency management. 

PMID- 24923943
TI  - Summary of: Continuing professional development and application of knowledge from
      research findings: a qualitative study of general dental practitioners.

PMID- 24923944
TI  - Summary of: Over-the-counter (OTC) bruxism splints available on the Internet.

PMID- 24923959
TI  - William David Stalley.

PMID- 24923960
TI  - Wilfred George Selley.

PMID- 24923961
TI  - Continuing professional development and application of knowledge from research
      findings: a qualitative study of general dental practitioners.
AB  - OBJECTIVES: To explore general dental practitioners' opinions about continuing
      professional development (CPD) and potential barriers to translating research
      findings into clinical dental practice. DESIGN: Qualitative focus group and
      interviews. SUBJECTS, SETTING AND METHODS: Four semi-structured interviews and a
      single focus group were conducted with 11 general dental practitioners in North
      East England. OUTCOME MEASURE: Transcripts were analysed using the constant
      comparative method to identify emergent themes. RESULTS: The key theme for
      practitioners was a need to interact with colleagues in order to make informed
      decisions on a range of clinical issues. For some forms of continuing
      professional development the value for money and subsequent impact upon clinical
      practice was limited. There were significant practice pressures that constrained
      the ability of practitioners to participate in certain educational activities.
      The relevance of some research findings and the formats used for their
      dissemination were often identified as barriers to their implementation in
      general dental practice. CONCLUSIONS: There are a number of potential barriers
      that exist in general dental practice to the uptake and implementation of
      translational research. CPD plays a pivotal role in this process and if new
      methods of CPD are to be developed consideration should be given to include
      elements of structured content and peer review that engages practitioners in a
      way that promotes implementation of contemporary research findings.

PMID- 24923962
TI  - Over-the-counter (OTC) bruxism splints available on the Internet.
AB  - BACKGROUND: Some individuals may now be bypassing their dentists for treatment of
      bruxism. Self-diagnosed, self-adjusted and self-monitored consumers can access
      over-the-counter (OTC) bruxism splints via the Internet. While some may regard
      this market as benefiting consumers there are potential pitfalls that need to be
      highlighted. These include unevidenced claims of efficacy. OBJECTIVE: To survey
      OTC bruxism splints available to individuals in the UK via the Internet,
      categorise their characteristics, and determine any web-based claims or safety
      warnings. MATERIALS AND METHODS: An Internet search was made of OTC bruxism
      splints available in the UK. The following information was recorded for each OTC
      splint: the name of the manufacturer, name of the device, its UK price and any
      claims and safety warnings made either on a major UK retail website or via other
      UK web retail outlets. In addition, a note was made of any web-based mention of
      'CE marking', indicating compliance with the EC Medical Devices Directive's
      requirements for safety, quality and performance. RESULTS: Safety information is
      notable for its paucity and is totally lacking on many Internet sites. However,
      manufacturers are not obliged to display safety information on the Internet, but
      it must be provided with the product. A search of the MAUDE database showed a
      number of potentially serious adverse events associated with these splints
      including choking hazards, tissue damage and occlusal changes. None of the splint
      designs assure full occlusal coverage. CONCLUSIONS: As with any partial coverage
      appliance, if worn for protracted periods there may be a risk of unwanted tooth
      movement. Dentists should report or assist patients with reporting suspected
      adverse events with OTC splints to the relevant competent authority. In the UK
      this is the Medicines and Healthcare Products Regulatory Agency (MHRA).

PMID- 24923963
TI  - Characteristics and referral of head and neck cancer patients who report chewing
      and dental issues on the Patient Concerns Inventory.
AB  - BACKGROUND: Patients experience considerable dental-related difficulties
      following head and neck cancer (HNC) treatment including problems with chewing,
      dry mouth, oral hygiene, appearance and self-esteem. These can go unrecognised in
      busy follow-up clinics. The Patient Concerns Inventory (PCI) is specifically for
      HNC patients, enabling them to select topics they wish to discuss and members of
      the multi-professional team they want to see. AIM: The study aimed to identify
      the clinical characteristics of patients raising dental concerns on the PCI and
      to explore the outcome of onward referral. Assessments included the PCI and the
      University of Washington Quality of Life Questionnaire (UW-QOL) version 4, with
      clinic details collated from hospital and cancer databases. METHOD: PCI data were
      obtained from 317 HNC patients between 2007 and 2011. Their mean age was 63 years
      and 60% were male. Most had oral squamous cell carcinoma and underwent surgery.
      The median (IQR) time from treatment to first PCI was 13 (4-42) months. RESULTS:
      Three comparison groups were identified: patients with significant chewing
      problems, patients without significant chewing problems who wanted to discuss
      dental-related concerns and patients without significant chewing problems who did
      not want to discuss such concerns. Fifty-two percent reported either a
      significant chewing problem on the UW-QOL or a wish to discuss dental-related
      concerns. A quarter specifically asked to talk to a dental professional. Clinical
      characteristics significantly associated with dental issues were stage, primary
      treatment and free flap reconstruction. Clinic letters were copied to only 10% of
      general dental practitioners (GDPs). CONCLUSION: Better communication with GDPs
      is essential.

PMID- 24923964
TI  - Laparoendoscopic single-site retroperitoneoscopic nephrectomy for giant
      hydronephrosis.
AB  - PURPOSE: To report our experience and assess the feasibility and safety of
      laparoendoscopic single-site (LESS) retroperitoneoscopic nephrectomy for giant
      hydronephrosis. PATIENTS AND METHODS: Between July 2011 and April 2013, 22
      patients underwent LESS retroperitoneoscopic nephrectomy for giant hydronephrosis
      with nonfunctioning kidneys. A reusable elastic single-port device was inserted
      through the 2.5-cm incision at the midpoint between the costal arch and iliac
      crest on the midaxillary line. A rigid, 10-mm, 30 degrees  extra-long laparoscope
      was introduced for monitoring, and a combination of lengthened prebent and
      conventional laparoscopic instruments was used for handling. The operation
      procedure was similar to the conventional retroperitoneal laparoscopic
      nephrectomy. RESULTS: LESS retroperitoneoscopic nephrectomy was completed in all
      patients without conversion to open surgery and the additional placement of
      ports. The mean operative time was 98 minutes (range 77-146), and estimated blood
      loss was 45 mL (range 20-120). No major intraoperative complications occurred.
      The postoperative period was uneventful in all patients and the mean hospital
      stay was 3.4 days (range 2-7). CONCLUSIONS: LESS retroperitoneoscopic nephrectomy
      for giant hydronephrosis is technically feasible and safe for selected patients.
      The combination of conventional and prebent laparoscopic instruments represents
      an attractive option for retroperitoneoscopic LESS.

PMID- 24923965
TI  - Structure, composition and metagenomic profile of soil microbiomes associated to
      agricultural land use and tillage systems in Argentine Pampas.
AB  - Agriculture is facing a major challenge nowadays: to increase crop production for
      food and energy while preserving ecosystem functioning and soil quality.
      Argentine Pampas is one of the main world producers of crops and one of the main
      adopters of conservation agriculture. Changes in soil chemical and physical
      properties of Pampas soils due to different tillage systems have been deeply
      studied. Still, not much evidence has been reported on the effects of
      agricultural practices on Pampas soil microbiomes. The aim of our study was to
      investigate the effects of agricultural land use on community structure,
      composition and metabolic profiles on soil microbiomes of Argentine Pampas. We
      also compared the effects associated to conventional practices with the effects
      of no-tillage systems. Our results confirmed the impact on microbiome structure
      and composition due to agricultural practices. The phyla Verrucomicrobia,
      Plactomycetes, Actinobacteria, and Chloroflexi were more abundant in non
      cultivated soils while Gemmatimonadetes, Nitrospirae and WS3 were more abundant
      in cultivated soils. Effects on metabolic metagenomic profiles were also
      observed. The relative abundance of genes assigned to transcription, protein
      modification, nucleotide transport and metabolism, wall and membrane biogenesis
      and intracellular trafficking and secretion were higher in cultivated fertilized
      soils than in non cultivated soils. We also observed significant differences in
      microbiome structure and taxonomic composition between soils under conventional
      and no-tillage systems. Overall, our results suggest that agronomical land use
      and the type of tillage system have induced microbiomes to shift their life
      history strategies. Microbiomes of cultivated fertilized soils (i.e. higher
      nutrient amendment) presented tendencies to copiotrophy while microbiomes of non
      cultivated homogenous soils appeared to have a more oligotrophic life-style.
      Additionally, we propose that conventional tillage systems may promote
      copiotrophy more than no-tillage systems by decreasing soil organic matter
      stability and therefore increasing nutrient availability.

PMID- 24923967
TI  - 'Anxiety' in laboratory rodents: a brief review of some recent behavioural
      developments.
AB  - It is clearly difficult to determine which of the multitude of behavioural and
      physiological indices provides the most reliable indicator of 'stress' in any
      particular animal. Although 'fear' and 'anxiety' have obvious survival value in
      feral animals, the induction of intense or chronic states of fearfulness are
      likely to account for much of the 'stress' which concerns applied ethologists,
      animal welfare students and keepers of animal collections etc. Recent
      developments applying ethoexperimental approaches (combining ethology and
      experimental psychology) to the study of behavioural indicators of anxiety in
      rodents, seemingly provide useful indicators of 'stress'. The areas looked at are
      predator-prey interactions, studies on ultrasonic 'distress calls' in neonates
      and analyses of fearful defensive behaviour in dyadic encounters. 

PMID- 24923966
TI  - Clinical and metabolic evaluation of patients with history of renal calculi in
      Qazvin, Iran.
AB  - BACKGROUND: Nephrolithiasis is a common clinical disorder with significant health
      and economic burden. We conducted this study to evaluate clinical and metabolic
      parameters in adult patients with history of renal calculi. MATERIALS AND
      METHODS: A total of 213 patients with history of nephrolithiasis participated in
      this study. Evaluation included the measurement of serum calcium, uric acid,
      parathormone, renal function tests, urinalysis, and urinary tests for cystinuria.
      Also, parameters such as volume, creatinine, calcium, uric acid, citrate, and
      oxalate levels were measured on 24-h urine. All patients underwent urinary tract
      system sonography. RESULTS: Of total patients, 52% were males and 48% females.
      The mean age was 45.16 +/- 13.16 years. Also, 51.2% of subjects had positive
      family history of nephrolithiasis. The mean body mass index was (26.8 +/- 4.2)
      kg/m(2). The mean 24-h urine biochemical profiles were volume (1,748 +/- 860 ml),
      Ca (183 +/- 115), uric acid (544 +/- 220), citrate (490 +/- 351), and oxalate
      (17.1 +/- 15.3) mg/day; urine calcium to creatinine ratio (0.15 +/- 0.10) mg/mg,
      and urine calcium to weight ratio (2.4 +/- 1.7) mg/kg. While there were weak
      positive correlations between the body mass index and urinary calcium (r = 0.101,
      P < 0.001) and uric acid (r = 0.200, P < 0.001), a weak negative correlation with
      urine pH (r = -0.104, P < 0.001) was found. CONCLUSIONS: Urine calcium, uric
      acid, and oxalate excretion were low in our patients while urine citrate was
      relatively high. Higher BMI maybe a risk factor for nephrolithiasis.

PMID- 24923968
TI  - The specificity of social stress.
AB  - This paper attempts to clarify the concept of "social stress" as implicitly
      understood in the ethological literature. With respect to the general
      characteristics of stressors and stress responses, the concept when applied to
      crowding or to encounters with unfamiliar conspecifics does not appear to denote
      a specific process. The concept is more specific when it refers to the
      psychological (emotional, perceptive or cognitive) processes that accompany
      "behavioural stress", e.g. agonistic interactions and subordination experience.
      The concept of "sociological stress" is proposed to denote the very specific
      process whereby stress responses of individuals result from a group's social
      structure, and whereby the former determine the latter via behavioural
      interactions and the other types of couplings (e.g. perceptive) between the group
      members. Finally, it is submitted that social stress at the group level may not
      be adequately reflected by traditional hormonal indicators of physiological
      stress. 

PMID- 24923969
TI  - Stress, stereotypies and welfare.
AB  - Stereotypies have been attributed various functions ranging from coping with
      conflict and frustration to self narcotization via activation of endogenous
      opioids. However, the evidence in favor of these postulated functions is far from
      conclusive. Stereotypies are more likely to represent the outward expression of
      disturbances in brain neural structures controlling persistence of behaviour in
      response to environmental precipitating factors interacting with individual
      predisposing factors. 

PMID- 24923970
TI  - Stereotypies and suffering.
AB  - Stereotypies often develop in environments that independent evidence shows cause
      poor welfare. Thus the development od stereotypies indicates that well-being has
      probably been poor, with the animal motivated to show a behaviour pattern that it
      could not perform normally or to completion. The continued performance of
      stereotypies may also indicate current suffering. However, an individual or
      population's degree of stereotypy does not necessarily correspond to the degree
      to which its well-being or welfare is impaired. This would require individual
      differences in stereotypy level to be the product of motivational differences and
      nothing else. In fact, they are also likely to be influenced by an animal's
      tendency to respond to the eliciting aspects of its environment with active
      behaviour rather than in a more inactive way. Stereotypy levels are also likely
      to be influenced by the general propensity of the individual to develop
      inflexible behavioural routines. Furthermore, as a stereotypy develops and
      becomes more habit-like it may be performed in circumstances where well-being is
      not at stake. Thus when comparing animals, lower levels of stereotypy do not
      necessarily reflect better well-being. General rules about the levels of
      stereotypy that are deemed "acceptable" from a welfare point of view are of
      limited use in reducing animal suffering unless they take take these factors into
      account. There is a great need for more research into the developmental processes
      responsible for stereotypies. 

PMID- 24923971
TI  - Assessing welfare and suffering.
AB  - Poor welfare occurs in situations in which the effects on the animal are adverse
      in that there is reduced fitness or clear indications that fitness will be
      reduced, ie. the animal is stressed, and in situations where the individual has
      difficulty in coping with its environment. Welfare is improved by increased
      control over the environment. There is a wide variety of measurements of welfare.
      Behaviour measurements are of particular importance but should be combined with
      physiological, immunological, injury, disease, mortality risk, growth and
      reproduction measures in order to obtain complete information. Suffering is an
      important aspect of poor welfare but welfare can be poor in the absence of
      suffering. There are many measures of poor welfare which do not necessarily
      indicate suffering. Welfare should not be defined solely in terms of subjective
      experiences. 

PMID- 24923972
TI  - Coping styles of tethered sows.
AB  - Behaviour of 20 non-pregnant primiparous sows was observed from the moment of
      first tethering till 2 hours thereafter, and after being tethered for 1 and 2
      months. After 2 months of tethering the sows could be divided into 2 distinct
      groups; (1) high stereotypers and (2) low stereotypers. Sows that resisted most
      at first tethering showed the lowest level of stereotyping after 1 and 2 months
      of tethering. High resisting sows may experience the uncontrollability of first
      tethering most drastically and develop a state of helplessness. Low resisting
      sows may accept tethering easier and adapt by means of developing stereotypies.
      Low stereotyping sows were more alert after 1 and 2 months of tethering than high
      stereotyping ones. Heart rate measurements showed that high stereotyping sows had
      lower mean heart-rates after feeding (when stereotyping is most pronounced) than
      low stereotyping ones. This difference was already present before tethering when
      the sows were loose-housed. The results show differences in styles of coping in
      sows that become more visible during tethering. 

PMID- 24923973
TI  - Relationship between plasma cortisol and stereotypic activities in pigs.
AB  - The relationship between the performance of post-feeding stereotypic behaviour
      and plasma cortisol levels and the effect of prevention of stereotypic behaviour
      on plasma cortisol levels were studied in chronically restrained sows. In
      experiment 1 sows classified as high or low stereotypers on the basis of time
      spent manipulating chain and behaviour directed to the nipple drinker were found
      not to differ in plasma cortisol levels. Removing the chain and nipple drinkers
      also did not affect cortisol concentrations of either group. In experiment 2
      detailed recordings were made by an automatic logging system of two major
      categories of stereotypy; chain manipulation and drinking. There were large
      individual differences in levels of both chain manipulation and drinking. Both
      activities showed a similar diurnal pattern, but average levels across
      individuals were not correlated. Both activities showed a continuous distribution
      across individuals and therefore a correlational rather than factorial analysis
      was used. Chain manipulation was not correlated to cortisol concentrations on any
      of the control days and removing the chain for one day (experiment 2A) or for
      seven days (experiment 2B) was also not accompanied by increased cortisol levels.
      However individuals showed a consistent cortisol response to chain removal as
      indicated by correlations between treatment days. Drinking showed a tendency to
      be negatively correlated to cortisol concentrations on control days. Long-term
      chain removal was accompanied by an increase in average drinking that showed a
      non-significant tendency to be negatively correlated to plasma cortisol on
      treatment days and thus may explain part of the consistency of response to chain
      removal. The lack of correlation between chain manipulation and plasma cortisol
      suggests that this activity does not serve to reduce plasma cortisol in
      chronically restrained sows. The relationship between drinking and cortisol need
      not necessarily reflect the coping capacity of this behaviour but may be a
      physiological consequence of the large amounts of water ingested. 

PMID- 24923974
TI  - Seasonal variation in stereotypic pacing in an American black bear Ursus
      americanus.
AB  - The behaviour of a male American black bear Ursus americanus was observed for
      over 2400 h across all seasons of the year. Stereotypic pacing was most frequent,
      oriented away from the exhibit, and performed mainly after feeding during the
      period May-July; from August-November pacing was oriented towards the exhibit and
      performed mainly around feeding time. Placing bear odors in the enclosure
      slightly reduced pacing and increased exploring/foraging in the late spring.
      Hiding small food items in the exhibit almost completely eliminated pacing in the
      fall and replaced it with foraging. Comparison with seasonal changes in the
      behaviour of wild bears suggest that the stereotypy of this bear, and probably
      zoo bears in general, developed from two main primary behaviours that cannot be
      performed in a barren zoo environment: mate-seeking behaviour predominating in
      the late spring and foraging behaviour in the late summer and fall. 

PMID- 24923975
TI  - Early experience with the farm environment and effects on later behaviour in
      silver Vulpes vulpes and blue foxes Alopex lagopus.
AB  - Seventy-one silver fox and 141 blue fox cubs were exposed to constant visual
      contact with the farm environment from the age of 2 to 8 weeks. The exposure
      consisted in opening a door in the nest box facing the feed gang-way. Control
      cubs (33 silver and 77 blue foxes) were reared in similar but closed nest boxes.
      All cubs were tested at the age of 12-16 weeks and again at the age of 23-28
      weeks; during these tests the behavioural responses of the foxes towards a human
      being were recorded. Both tests showed that in the two species, the early
      experience with the farm environment reduced the fear responses of the foxes
      towards humans. The conclusion of the study was that early visual experience with
      the farm environment makes the foxes better adapted to captivity, including the
      presence of humans. 

PMID- 24923976
TI  - Effects of whole-year nest boxes on cortisol, circulating leucocytes, exploration
      and agonistic behaviour in silver foxes.
AB  - An experiment was carried out for a period of 2 years, using 50 silver fox vixens
      kept in cages with nest boxes, and 50 vixens kept in barren wire cages without
      any sort of equipment. At the end of the experiment, the animals living with
      access to nest boxes had lower base levels of cortisol and eosinophils, and
      higher base levels of lymphocytes. They also were less fearful towards humans and
      more active/ explorative in an open field test. It was concluded that these
      animals were less stressed than those living without nest boxes, a result that
      could have practical implications for the welfare of foxes during everyday life
      at the farm. 

PMID- 24923977
TI  - Effects of immobility stress and food restriction on stereotypies in low and high
      stereotyping female ranch mink.
AB  - Two experiments were conducted to examine the effects of repeated immobilisations
      and food restriction on normal activity and stereotypies in low and high
      stereotyping female ranch mink. Repeated immobilisations had immediate inhibitory
      effects on normal activity and stereotypies in both groups, whereas food
      restriction had the opposite immediate effects. Subsequent to both
      immobilisations and food restriction, stereotypies were increased, whereas normal
      activities returned to pre-experimental levels. Repeated immobilisations were
      followed by increases in cortisol levels in both low and high stereotyping
      females. High stereotyping females had lower baseline cortisol levels than low
      stereotypers but tended to show higher cortisol responses to immobilisations.
      These results indicate that stressful experiences may affect stereotypies, but
      that the direction of the changes depends on type of stressor as well as the
      duration of exposure to the stressor. It is moreover suggested that stereotypies
      can be emancipated. 

PMID- 24923979
TI  - Summary and perspectives: individual patterns of stress responses.

PMID- 24923978
TI  - Effect of environmental stress and immobilization on stress physiological
      variables in farmed mink.
AB  - The effect of cage size and nest box environment on plasma cortisol, number of
      eosinophil leucocytes, and on frequency of leucocyte groups was measured on 132
      farmed mink. The experiment included three cage sizes (0.10 m(2), 0.27 m(2), and
      1.1 m(2)) and cages with and without nest boxes. Furthermore, the effect of daily
      immobilization a mink trap for 5 or 30 min. over periods of 10 days was
      demonstrated. The effect of daily immobilization for 5 min. was an unchanged
      cortisol response to immobilization from day 1 to day 10, no effect on eosinophil
      leucocyte level, and a decrease of H/L-ratio from day 1 to day 10. After 30 min.
      daily immobilization the cortisol response decreased from day 1 to day 10, the
      eosinophil leucocyte level decreased, and the H/L-ratio increased from day 1 to
      day 10. Mink females in cages without nest boxes had a higher plasma cortisol
      level, a lower level of eosinophil leucogytes, and a higher H/L-ratio than mink
      in cages with nest boxes. No effect of cage sizes was seen on the physiological
      variables used. A pronounced seasonal variation has been shown in the
      physiological variables used. The results made it possible to conclude that the
      duration of individual immobility sessions is of consequence to the physiological
      effect of immobilization. The physiological stress level increased when farmed
      mink were deprived of the use of nest boxes. The effect of keeping mink in cages
      without nest boxes was similar to daily immobilization for 30 min. with regard to
      both the level of eosinophil leucocytes, the relative distribution of leucocyte
      types, and the H/L-ratio. 

PMID- 24923980
TI  - Symmetry of the fornix using diffusion tensor imaging.
AB  - PURPOSE: To: 1) Present fornix tractography in its entirety for 20 healthy
      individuals to assess variability. 2) Provide individual and groupwise whole
      tract diffusion parameter symmetry assessments prior to clinical application. 3)
      Compare whole tract diffusion parameter assessments with tract-based spatial
      statistics (TBSS). MATERIALS AND METHODS: Diffusion tensor imaging (DTI) data
      were acquired on a 3T Siemens magnetic resonance imaging (MRI) system using a
      single-shot spin echo planar imaging (EPI) sequence. Individual fornix
      tractography was conducted and whole tract diffusion parameter symmetries
      assessed. Whole tract results were compared with asymmetry contrasts conducted
      with voxelwise statistical analysis of diffusion parameters using TBSS. RESULTS:
      The fornix tract could be visualized in its entirety including the columns, body,
      crura, and fimbria. Contrary to the crus and body, there were some tractography
      inconsistencies of the columns and fimbria across subjects. Although whole tract
      diffusion parameter asymmetries were nonsignificant, fractional anisotropy (FA)
      values bordered on statistical significance (P = 0.052). Using TBSS, significant
      FA asymmetries were identified (P <= 0.01, corrected). CONCLUSION: The findings
      demonstrate consistency of fornix tractography as well as some variability in the
      columns and fimbria. While parametric assessment demonstrates diffusion parameter
      symmetry, permutation-based TBSS analysis reveals significant FA asymmetries in
      the crura and fimbriae.

PMID- 24923981
TI  - Differential effects of amphetamine and GBR-12909 on orolingual motor function in
      young vs aged F344/BN rats.
AB  - RATIONALE: Orolingual motor deficits, such as dysarthria and dysphagia,
      contribute to increased morbidity and mortality in the elderly. In preclinical
      studies, we and others have reported age-related decreases in tongue motility in
      both F344 and F344/BN rats. The fact that these deficits are associated with
      nigrostriatal dopamine (DA), tissue measures suggest that increasing dopamine
      function might normalize tongue motility. OBJECTIVE: The purpose of the current
      study was to determine whether two indirect dopamine agonists with locomotor
      enhancing effects, d-amphetamine (amphetamine; 1 and 2 mg/kg) and GBR-12909 (5,
      10, and 20 mg/kg), can improve tongue motility in aged F344/BN rats. METHODS:
      Young (6 months) and aged (30 months) F344/BN rats licked water from an isometric
      force disc so that tongue motility (licks/second) and tongue force could be
      measured as a function of age and drug dose. RESULTS: Consistent with our
      previous studies, tongue force was greater and tongue motility was lower in the
      aged group. Tongue motility was increased by amphetamine but not by GBR-12909.
      Amphetamine decreased peak tongue force, primarily in the young group. GBR-12909
      did not affect tongue force. GBR-12909 increased the number of licks/session in
      the young group but not in the aged group, while amphetamine increased this
      measure in both groups. CONCLUSION: These results demonstrate differential
      effects of these drugs on orolingual motor function and suggest that blocking DA
      uptake is insufficient to increase tongue motility in aging.

PMID- 24923982
TI  - Negative reinforcement via motivational withdrawal is the driving force behind
      the transition to addiction.

PMID- 24923983
TI  - Persistent modification of forebrain networks and metabolism in rats following
      adolescent exposure to a 5-HT7 receptor agonist.
AB  - RATIONALE: The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission
      system with a proposed role in neural plasticity and in mood, cognitive or sleep
      regulation. OBJECTIVES: We investigated long-term consequences of sub-chronic
      treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5
      HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day). METHODS: We evaluated behavioural
      changes as well as forebrain structural/functional modifications by in vivo
      magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology.
      RESULTS: Adult rats pre-treated during adolescence showed reduced anxiety-related
      behaviour, in terms of reduced avoidance in the light/dark test and a less
      fragmented pattern of exploration in the novel object recognition test. Diffusion
      tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala,
      increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial
      (D||) together with increased radial (D?) diffusivity in the nucleus accumbens
      (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by
      ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased
      strength of connectivity within and between "limbic" and "cortical" loops, with
      affected cross-correlations between amygdala, NAcc and Hip. The latter displayed
      enhanced connections through the dorsal striatum (dStr) to dorso-lateral
      prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased
      between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC)
      and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211
      exposure increased glutamate and total creatine in the adult Hip. CONCLUSIONS:
      Persistent MR-detectable modifications indicate a rearrangement within forebrain
      networks, accounting for long-lasting behavioural changes as a function of
      developmental 5-HT7-R stimulation.

PMID- 24923984
TI  - Behavioural and neurochemical assessment of salvinorin A abuse potential in the
      rat.
AB  - RATIONALE: Salvinorin A is a recreational drug derived from Salvia divinorum, a
      sage species long used as an entheogen. While salvinorin A has potent
      hallucinogenic properties, its abuse potential has not been assessed consistently
      in controlled behavioural and neurochemical studies in rodents. OBJECTIVE: This
      study aimed to assess salvinorin A abuse potential by measuring its capacity to
      establish and maintain self-administration behaviour and to modify dopamine (DA)
      levels in the nucleus accumbens (NAcc) of rats. RESULTS: Male Lister Hooded (LH)
      and Sprague-Dawley (SD) rats were allowed to self-administer salvinorin A (0.5 or
      1.0 MUg/kg/infusion) intravenously 2 h/day for 20 days under a continuous
      schedule of reinforcement and lever pressing as operandum. LH rats discriminated
      between the active and inactive levers but did not reach the acquisition
      criterion for stable self-administration (>=12 active responses vs <=5 inactive
      responses for at least 5 consecutive days). SD rats discriminated between the two
      levers at the lower dose only but, like LH rats, never acquired stable self
      administration behaviour. Systemic salvinorin A increased extracellular DA in the
      NAcc shell of both LH (at >=40 MUg/kg) and SD rats (at >=5 MUg/kg), but injection
      into the ventral tegmental area (VTA) induced no significant change in NAcc DA
      concentration in LH rats and only brief elevations in SD rats. CONCLUSIONS:
      Salvinorin A differs from other commonly abused compounds since although it
      affects accumbal dopamine transmission, yet it is unable, at least at the tested
      doses, to sustain stable intravenous self-administration behaviour.

PMID- 24923985
TI  - Accounting for sex-related differences in the estimation of breath alcohol
      concentrations using transdermal alcohol monitoring.
AB  - RATIONALE: Previously, we reported methods to estimate peak breath alcohol
      concentrations (BrAC) from transdermal alcohol concentrations (TAC) under
      conditions where alcohol consumption was controlled to produce similar BrAC
      levels in both sexes. OBJECTIVE: This study characterized differences in the
      relationship between BrAC and TAC as a function of sex and developed a model to
      predict peak BrAC that accounts for known sex differences in peak BrAC. METHODS:
      TAC and BrAC were monitored during the consumption of a varying number of beers
      on different days. Both men (n=11) and women (n=10) consumed one, two, three,
      four, and five beers at the same rate in a 2-h period. Sex and sex-related
      variables were considered for inclusion in a multilevel model to develop an
      equation to estimate peak BrAC levels from TAC. RESULTS: While peak BrAC levels
      were significantly higher in women than men, sex differences were not significant
      in observed TAC levels. This lack of correspondence was evidenced by significant
      sex differences in the relationship between peak TAC and peak BrAC. The best
      model to estimate peak BrAC accounted for sex-related differences by including
      peak TAC, time-to-peak TAC, and sex. This model was further validated using
      previously collected data. CONCLUSIONS: The relationship between peak TAC and
      actual peak BrAC differs between men and women, and these differences can be
      accounted for in a statistical model to better estimate peak BrAC. Further
      studies are required to extend these estimates of peak BrAC to the outpatient
      environment where naturalistic drinking occurs.

PMID- 24923986
TI  - Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a
      randomized, double-blind, placebo-controlled trial (a Positive and Negative
      Syndrome Scale, five-factor analysis).
AB  - BACKGROUND: Treating schizophrenia patients who fail to respond to antipsychotics
      is a major challenge, and the percentage of treatment-resistant patients is
      estimated to be 20-25 %. Recent studies indicate that yokukansan (YKS; D2 and
      5HT1A partial agonist and 5HT2A and glutamate antagonist) to be safe and useful
      in treating behavioral and psychological symptoms associated with dementia and
      other neuropsychiatric conditions. We aimed at evaluating both the efficacy and
      safety of YKS in patients with treatment-resistant schizophrenia. METHODS: This
      randomized, multicenter, double-blind, placebo-controlled study was conducted
      between May 2010 and August 2012. One hundred twenty antipsychotic-treated
      inpatients from 34 psychiatric hospitals in Japan were included. Patients were
      randomized to adjuvant treatment with YKS 7.5 g/day or placebo. During a 4-week
      follow-up, psychopathology was assessed using the Positive and Negative Syndrome
      Scale (PANSS) with five factors [excitement/hostility (P4, P7, G8, and G14),
      depression/anxiety (G1, G2, G3, G4, and G6), cognition (P2, N5, N7, G5, G10, G11,
      G12, G13, and G15], positive (P1, P3, P5, P6, and G9), and negative (N1, N2, N3,
      N4, N6, G7, and G16]]. Other assessments included, Clinical Global Impression
      Severity (CGI-S), Global Assessment of Functioning (GAF), and Drug-Induced
      Extrapyramidal Symptoms Scale (DIEPSS). The primary efficacy outcome was the
      change in PANSS five-factor scores. The secondary outcomes were changes in the
      scores of CGI-S. The analysis was made on a modified intention to treat basis
      with the help of a last observation carried forward method. RESULTS: YKS showed a
      tendency of superiority to placebo in reducing total all PANSS five-factor scores
      in treatment-resistant schizophrenia, but the difference was not statistically
      significant in total, depression/anxiety, cognition, positive, and negative
      factors. However, compared to the placebo group, the YKS group showed
      statistically significant improvements in the PANSS excitement/hostility factor
      scores (p<0.05). No substantial side effects were recorded. CONCLUSION: The
      results of the present study indicate YKS to be a potential adjunctive treatment
      strategy for treatment-resistant schizophrenia, particularly to improve
      excitement/hostility symptoms.

PMID- 24923988
TI  - Dynamically controlled one-pot synthesis of heterogeneous core-shell MOF single
      crystals using guest molecules.
AB  - A new mixed guest approach for the synthesis of heterogeneous core-shell MOF
      crystals was exemplified by one-pot assembly of photoactive guests into an
      anionic host framework. The formation mechanism, photophysical properties and
      oxygen gas sensing properties of as-synthesized core-shell MOF crystals were also
      investigated. 

PMID- 24923987
TI  - Levodopa administration modulates striatal processing of punishment-associated
      items in healthy participants.
AB  - RATIONALE: Appetitive and aversive processes share a number of features such as
      their relevance for action and learning. On a neural level, reward and its
      predictors are associated with increased firing of dopaminergic neurons, whereas
      punishment processing has been linked to the serotonergic system and to decreases
      in dopamine transmission. Recent data indicate, however, that the dopaminergic
      system also responds to aversive stimuli and associated actions. OBJECTIVES: In
      this pharmacological functional magnetic resonance imaging study, we investigated
      the contribution of the dopaminergic system to reward and punishment processing
      in humans. METHODS: Two groups of participants received either placebo or the
      dopamine precursor levodopa and were scanned during alternating reward and
      punishment anticipation blocks. RESULTS: Levodopa administration increased
      striatal activations for cues presented in punishment blocks. In an interaction
      with individual personality scores, levodopa also enhanced striatal activation
      for punishment-predictive compared with neutral cues in participants scoring
      higher on the novelty-seeking dimension. CONCLUSIONS: These data support recent
      indications that dopamine contributes to punishment processing and suggest that
      the novelty-seeking trait is a measure of susceptibility to drug effects on
      motivation. These findings are also consistent with the possibility of an
      inverted U-shaped response function of dopamine in the striatum, suggesting an
      optimal level of dopamine release for motivational processing.

PMID- 24923992
TI  - Work stress among nurses engaged in palliative care on general wards.
AB  - OBJECTIVE: The objective of the present study was to elucidate the work stress
      among nurses engaged in palliative care on general wards. The relationship
      between nurses' psychological characteristics and stress was the particular focus
      of this study in order to clarify the actual stress situation. METHODS: Nurses
      with >=3 years of experience in palliative care on general wards were surveyed
      with respect to their personal characteristics, work stress using a scale created
      by the authors, the Profile of Mood States (POMS) short version, and the Coping
      Inventory for Stressful Situations (CISS). Correlations between each derived
      variable and stress were tested. Variables found to be significant were set as
      independent variables, and multiple regression analysis was performed with
      overall stress as the dependent variable. RESULTS: A total of 402 nurses
      participated. The questionnaire response rate was 68.2%, with a valid response
      rate of 59.7%. The analysis involved 240 participants (96.7% female participants;
      mean age, 36.2 years old). Tension-Anxiety (POMS), Fatigue (POMS), Confusion
      (POMS), and Emotion-Oriented Coping (CISS) were the significant variables. On
      multiple regression analysis with these four variables, the coefficient of
      determination was R(2)  = 0.103, and the coefficient of determination adjusted
      for degrees of freedom was R(2)  = 0.087. Fatigue (POMS) (beta = 0.179, p < 0.05)
      and Emotion-Oriented Coping (CISS; beta = 0.197, p < 0.05) were found to be
      significantly related to stress among nurses providing palliative care on general
      wards. CONCLUSIONS: The stress among nurses engaged in palliative care on general
      wards can be predicted by the degree of 'fatigue' and 'emotion-oriented coping'.
      Mechanisms to address these issues are needed.

PMID- 24923990
TI  - Emerging mechanisms of mRNP remodeling regulation.
AB  - The assembly and remodeling of the components of messenger ribonucleoprotein
      particles (mRNPs) are important in determining the fate of a messenger RNA
      (mRNA). A combination of biochemical and cell biology research, recently
      complemented by genome-wide high-throughput approaches, has led to significant
      progress on understanding the formation, dynamics, and function of mRNPs. These
      studies also advanced the challenging process of identifying the evolving
      constituents of individual mRNPs at various stages during an mRNA's lifetime.
      While research on mRNP remodeling in general has been gaining momentum, there has
      been relatively little attention paid to the regulatory aspect of mRNP
      remodeling. Here, we discuss the results of some new studies and potential
      mechanisms for regulation of mRNP remodeling.

PMID- 24923993
TI  - Gender, age-related, and regional differences of the magnetization transfer ratio
      of the cortical and subcortical brain gray matter.
AB  - PURPOSE: To explore gender, age-related, and regional differences of
      magnetization transfer ratio (MTR) of brain cortical and subcortical gray matter
      (GM). MATERIALS AND METHODS: In all, 102 healthy subjects (51 women and 51 men;
      range 25-84 years) were examined with 3-mm thick MT images. We assessed MTR in
      automatically segmented GM structures including frontal, parietal-insular,
      temporal, and occipital cortex, caudate, pallidus and putamen, and cerebellar
      cortex. A general linear model analysis was conducted to ascertain the linear and
      quadratic relationship among the MTR and gender, age, and anatomical structure.
      RESULTS: The effect of gender was borderline (P = 0.07) in all GM structures
      (with higher MTR values in men), whereas age showed a significant linear as well
      as quadratic effect in all cortical and subcortical GM structures (P <= 0.001).
      Quadratic age-related decrease in MTR began at about 40 years of age. Mean and
      standard deviation (SD) of MTR had the following decreasing order: thalamus (58.3
      + 0.8), pallidus (56.8 +/- 1.3), caudate (55.5 +/- 1.6) and putamen (54.6 +/-
      1.1); temporal (56.8 +/- 0.9), parietal-insular (56.8 +/- 1.1), frontal (56.5 +/-
      1.1), occipital (55.4 +/- 1.0) and cerebellar (53.2 +/- 1.0) cortex. In post-hoc
      testing, all regional pairwise differences were statistically significant except
      pallidus vs. temporal or parietal-insular cortex, caudate vs. occipital cortex,
      frontal vs. parietal-insular or temporal cortex. CONCLUSION: MTR of the cortical
      and subcortical brain GM structures decreases quadratically after midlife and
      shows significant regional differences.

PMID- 24923991
TI  - Axonal localization of Ca2+-dependent activator protein for secretion 2 is
      critical for subcellular locality of brain-derived neurotrophic factor and
      neurotrophin-3 release affecting proper development of postnatal mouse
      cerebellum.
AB  - Ca2+-dependent activator protein for secretion 2 (CAPS2) is a protein that is
      essential for enhanced release of brain-derived neurotrophic factor (BDNF) and
      neurotrophin-3 (NT-3) from cerebellar granule cells. We previously identified
      dex3, a rare alternative splice variant of CAPS2, which is overrepresented in
      patients with autism and is missing an exon 3 critical for axonal localization.
      We recently reported that a mouse model CAPS2Deltaex3/Deltaex3 expressing dex3
      showed autistic-like behavioral phenotypes including impaired social interaction
      and cognition and increased anxiety in an unfamiliar environment. Here, we
      verified impairment in axonal, but not somato-dendritic, localization of dex3
      protein in cerebellar granule cells and demonstrated cellular and physiological
      phenotypes in postnatal cerebellum of CAPS2Deltaex3/Deltaex3 mice. Interestingly,
      both BDNF and NT-3 were markedly reduced in axons of cerebellar granule cells,
      resulting in a significant decrease in their release. As a result, dex3 mice
      showed developmental deficits in dendritic arborization of Purkinje cells,
      vermian lobulation and fissurization, and granule cell precursor proliferation.
      Paired-pulse facilitation at parallel fiber-Purkinje cell synapses was also
      impaired. Together, our results indicate that CAPS2 plays an important role in
      subcellular locality (axonal vs. somato-dendritic) of enhanced BDNF and NT-3
      release, which is indispensable for proper development of postnatal cerebellum. 

PMID- 24923994
TI  - Improving organizational capacity to address health literacy in public health: a
      rapid realist review.
AB  - OBJECTIVES: Despite the growing significance of health literacy to public health,
      relatively little is known about how organizational capacity may be improved for
      planning, implementing and sustaining health literacy interventions. This study
      aimed to connect decision makers in a public health agency with evidence of how
      organizational capacity may be improved for delivering health literacy services.
      STUDY DESIGN: A rapid realist review of published and grey literature was
      conducted by a partnership between the Public Health Agency of Canada (PHAC) and
      the InSource Research Group. METHODS: Realist review methodology attempts to
      understand what works for whom under what circumstances, and is characterized by
      its focus on strategies/interventions, contexts, mechanisms and their
      relationship to outcome. This review was completed in collaboration with a
      reference panel (comprised of a broad range of PHAC representatives) and an
      expert panel. Literature searching was conducted using three databases
      supplemented with bibliographic hand searches and articles recommended by panels.
      Data were extracted on key variables related to definitions,
      strategies/interventions associated with increased organizational capacity,
      contextual factors associated with success (and failure), mechanisms activated as
      a result of different strategies and contexts, key outcomes, and evidence cited.
      RESULTS: Strategies found to be associated with improved organizational capacity
      for delivering health literacy services may be classified into three domains: (1)
      government action; (2) organizational/practitioner action; and (3) partnership
      action. Government action includes developing policies to reinforce social norms;
      setting standards for education; conducting research; and measuring health
      literacy levels. Organizational/practitioner action relates to appropriate models
      of leadership (both high-level government engagement and distributed leadership).
      Innovative partnership action includes collaborations with media outlets, those
      producing electronic materials, community organizations and school-based
      programs. Contextual factors for success include positive leadership models,
      interorganizational relationships, and a culture committed to experimentation and
      learning. Potential mechanisms activated by strategies and contextual factors
      include increased visibility and recognition of health literacy efforts,
      enthusiasm and momentum for health literacy activities, reduced cognitive
      dissonance between vision and action, a sense of ownership for health literacy
      data, and creation of a common language and understanding. CONCLUSIONS:
      Government initiated interventions and policies are powerful strategies by which
      organizational capacity to improve health literacy may be affected. Using the
      foundations created by the government policy environment, organizations may
      improve the impact of health literacy interventions through supported distributed
      leadership.

PMID- 24923995
TI  - Concept mapping as a promising method to bring practice into science.
AB  - OBJECTIVE: Concept mapping is a method for developing a conceptual framework of a
      complex topic for use as a guide to evaluation or planning. In concept mapping,
      thoughts and ideas are represented in the form of a picture or map, the content
      of which is determined by a group of stakeholders. This study aimed to explore
      the suitability of this method as a tool to integrate practical knowledge with
      scientific knowledge in order to improve theory development as a sound basis for
      practical decision-making. METHOD: Following a short introduction to the method
      of concept mapping, five Dutch studies, serving different purposes and fields in
      public health, will be described. The aim of these studies was: to construct a
      theoretical framework for good regional public health reporting; to design an
      implementation strategy for a guideline for integral local health policy; to
      guide the evaluation of a local integral approach of overweight and obesity in
      youth; to guide the construction of a questionnaire to measure the quality of
      postdisaster psychosocial care; and to conceptualize an integral base for
      formulation of ambitions and targets for the new youth healthcare programme of a
      regional health service. RESULTS: The studies showed that concept mapping is a
      way to integrate practical and scientific knowledge with careful selection of
      participants that represent the different perspectives. Theory development can be
      improved through concept mapping; not by formulating new theories, but by
      highlighting the key issues and defining perceived relationships between topics.
      In four of the five studies, the resulting concept map was received as a sound
      basis for practical decision-making. CONCLUSIONS: Concept mapping is a valuable
      method for evidence-based public health policy, and a powerful instrument for
      facilitating dialogue, coherence and collaboration between researchers,
      practitioners, policy makers and the public. Development of public health theory
      was realized by a step-by-step approach, considering both scientific and
      practical knowledge. However, the external validity of the concept maps in place
      and time is of importance.

PMID- 24923996
TI  - Post-implementation review of pulse oximetry screening of well newborns in an
      Australian tertiary maternity hospital.
AB  - AIM: Despite there being evidence that pulse oximetry screening is better than
      clinical examination alone in early detection of CHD, implementation has been
      slow. The aim of this paper was to evaluate the practice after its implementation
      into routine care at Royal Prince Alfred Hospital in 2008. METHODS: A single
      pulse oximetry measurement was incorporated in the routine discharge newborn
      examination or, with early discharge, as a part of the Midwife Discharge Support
      Programme. An oxygen saturation level greater than or equal to 95% was considered
      normal, and a level less than 95%, confirmed on a repeat measure, triggered a
      review and examination by a consultant neonatal paediatrician. The saturation
      levels were recorded in the hospital database. Ascertainment of major CHD
      requiring surgery in the first 12 months was performed by searching the cardiac
      surgery database of the Heart Centre for Children. RESULTS: A total of 18 801
      babies were screened over a 42-month period. Of these, four babies with major CHD
      were diagnosed prior to discharge with the main clinical alert resulting from
      routine pulse oximetry screening (true positive). Of the 11 cases with saturation
      <95% but no CHD (false positive cases), six had respiratory pathology. One baby
      with normal saturation level needed surgery in the first year for a large
      ventricular septal defect (false negative). The false positive rate of pulse
      oximetry screening for CHD was 0.13% with sensitivity 80%, specificity of 99.8%,
      a positive predictive value of 13.3% and a negative predictive value of 99.9%.
      Nine additional echocardiogram were required over 42 months. CONCLUSIONS: These
      post-implementation data confirm that pulse oximetry screening increases early
      diagnosis of major CHD as well as other important pathology with a very low false
      positive rate and minimal requirement for extra echocardiograms. Pulse oximetry
      screening of apparently well newborns should become a standard of care.

PMID- 24923997
TI  - Association of increased travel distance to dialysis units with the risk of
      anemia in rural chronic hemodialysis elderly.
AB  - Geographic remoteness has been found to influence health-related outcomes
      negatively. As reported in the literature, rural dialysis patients have a higher
      risk of mortality with increasing travel distance to dialysis units. However, few
      studies have focused on the impact of travel distances on the development of
      dialysis complications. We utilized a prospectively collected chronic
      hemodialysis patient cohort from a rural regional hospital for analysis. Data on
      demographics, comorbidities, and serum laboratory results were obtained.
      Correlation analyses between travel distance to dialysis units and dialysis
      complications were conducted, and significantly correlated parameters were
      entered into multivariate logistic regression models to determine their exact
      associations. A total of 46 rural chronic hemodialysis patients were enrolled,
      with an average age higher than others in the literature. Significant correlation
      was found between travel distance and serum hemoglobin levels (R(2) = -0.34, P
      value = 0.029). Multivariate logistic regression found that every 1 km increase
      in travel distance was associated with an increased risk of anemia (hemoglobin <9
      g/dL) (odds ratio 1.46; P value = 0.01). Sensitivity analyses further showed that
      the associated risk was partially attenuated by serum albumin (odds ratio 1.83; P
      value = 0.07) and ferritin (odds ratio 1.39; P value = 0.08) levels. This is the
      first study to demonstrate the association between increased travel distance to
      dialysis units and the risk of anemia in chronic dialysis patients, especially
      elderly. Malnutrition, inflammation, and atherosclerosis syndrome could be
      partially responsible for the observed association. Further research is required
      to confirm our findings.

PMID- 24923998
TI  - Comparative performance of novel self-sampling methods in detecting high-risk
      human papillomavirus in 30,130 women not attending cervical screening.
AB  - We determined whether the participation rate for a brush-based cervicovaginal
      self-sampling device is noninferior to the participation rate for a lavage-based
      one for testing for hrHPV (high-risk human papillomavirus). Additionally,
      positivity rates for hrHPV, the detection rates for cervical intraepithelial
      neoplasia grades 2 and 3 or worse (CIN2+/3+), and user comfort were compared. A
      total of 35,477 non-responders of the regular cervical screening program aged 33
      63 years were invited to participate. Eligible women (n = 30,130) were randomly
      assigned to receive either a brush-based or a lavage-based device, and a
      questionnaire for reporting user convenience. Self-sampling responders testing
      hrHPV-positive were invited for a physician-taken sample for cytology; triage
      positive women were referred for colposcopy. A total of 5,218 women participated
      in the brush-based sampling group (34.6%) and 4809 women in the lavage-based
      group (31.9%), i.e. an absolute difference of 2.7% (95%CI 1.8-4.2). The hrHPV
      positivity rates in the two groups were identical (8.3%, relative risk (RR) 0.99,
      95%CI 0.87-1.13). The detection of CIN2+ and CIN3+ in the brush group (2.0% for
      CIN2+; 1.3% for CIN3+) was similar to that in the lavage group (1.9% for CIN2+;
      1.0% for CIN3+) with a cumulative RR of 1.01, 95%CI 0.83-1.24 for CIN2+ and 1.25,
      95%CI 0.92-1.70 for CIN3+. The two self-sampling devices performed similarly in
      user comfort. In conclusion, offering a brush-based device to non-responders is
      noninferior to offering a lavage-based device in terms of participation. The two
      self-sampling methods are equally effective in detecting hrHPV, CIN2+/CIN3+ and
      are both well accepted. 

PMID- 24923999
TI  - The MC-DFT approach including the SCS-MP2 energies to the new Minnesota-type
      functionals.
AB  - We have applied the multicoefficient density functional theory (MC-DFT) to four
      recent Minnesota functionals, including M06-2X, M08-HX, M11, and MN12-SX on the
      performance of thermochemical kinetics. The results indicated that the accuracy
      can be improved significantly using more than one basis set. We further included
      the SCS-MP2 energies into MC-DFT, and the resulting mean unsigned errors (MUEs)
      decreased by approximately 0.3 kcal/mol for the most accurate basis set
      combinations. The M06-2X functional with the simple [6-311+G(d,p)/6-311+G(2d,2p)]
      combination gave the best performance/cost ratios for the MC-DFT and MC-SCS
      MP2|MC-DFT methods with MUE of 1.58 and 1.22 kcal/mol, respectively.

PMID- 24924001
TI  - Precis of Unified theories of cognition.
AB  - The book presents the case that cognitive science should turn its attention to
      developing theories of human cognition that cover the full range of human
      perceptual, cognitive, and action phenomena. Cognitive science has now produced a
      massive number of high-quality regularities with many microtheories that reveal
      important mechanisms. The need for integration is pressing and will continue to
      increase. Equally important, cognitive science now has the theoretical concepts
      and tools to support serious attempts at unified theories. The argument is made
      entirely by presenting an exemplar unified theory of cognition both to show what
      a real unified theory would be like and to provide convincing evidence that such
      theories are feasible. The exemplar is SOAR, a cognitive architecture, which is
      realized as a software system. After a detailed discussion of the architecture
      and its properties, with its relation to the constraints on cognition in the real
      world and to existing ideas in cognitive science, SOAR is used as theory for a
      wide range of cognitive phenomena: immediate responses (stimulus-response
      compatibility and the Sternberg phenomena); discrete motor skills (transcription
      typing); memory and learning (episodic memory and the acquisition of skill
      through practice); problem solving (cryptarithmetic puzzles and syllogistic
      reasoning); language (sentence verification and taking instructions); and
      development (transitions in the balance beam task). The treatments vary in depth
      and adequacy, but they clearly reveal a single, highly specific, operational
      theory that works over the entire range of human cognition, SOAR is presented as
      an exemplar unified theory, not as the sole candidate. Cognitive science is not
      ready yet for a single theory - there must be multiple attempts. But cognitive
      science must begin to work toward such unified theories. 

PMID- 24924000
TI  - Dark matter RNA illuminates the puzzle of genome-wide association studies.
AB  - In the past decade, numerous studies have made connections between sequence
      variants in human genomes and predisposition to complex diseases. However, most
      of these variants lie outside of the charted regions of the human genome whose
      function we understand; that is, the sequences that encode proteins.
      Consequently, the general concept of a mechanism that translates these variants
      into predisposition to diseases has been lacking, potentially calling into
      question the validity of these studies. Here we make a connection between the
      growing class of apparently functional RNAs that do not encode proteins and whose
      function we do not yet understand (the so-called 'dark matter' RNAs) and the
      disease-associated variants. We review advances made in a different genomic
      mapping effort - unbiased profiling of all RNA transcribed from the human genome 
      and provide arguments that the disease-associated variants exert their effects
      via perturbation of regulatory properties of non-coding RNAs existing in
      mammalian cells.

PMID- 24924002
TI  - Unified cognitive theory: You can't get there from here.

PMID- 24924003
TI  - Reframing the problem of intelligent behavior.

PMID- 24924004
TI  - A unified theory for psychologists?

PMID- 24924005
TI  - Toward unified cognitive theory: The path is well worn and the trenches are deep.

PMID- 24924006
TI  - Re-membering cognition.

PMID- 24924007
TI  - Active symbols, limited storage and the power of natural intelligence.

PMID- 24924008
TI  - Unified cognitive theory is not comprehensive.

PMID- 24924009
TI  - Is Unified theories of cognition good strategy?

PMID- 24924010
TI  - A cognitive theory without inductive learning.

PMID- 24924011
TI  - SOAR as a world view, not a theory.

PMID- 24924013
TI  - Unified cognitive theory: Having one's apple pie and eating it.

PMID- 24924012
TI  - A psychologically implausible architecture that is always conscious, always
      active.

PMID- 24924014
TI  - Unifying congnition: Has it all been put together?

PMID- 24924015
TI  - Unified cognition misses language.

PMID- 24924016
TI  - Unified theories must explain the codependencies among perception, cognition and
      action.

PMID- 24924017
TI  - Unified psychobiological theory.

PMID- 24924018
TI  - How human is SOAR?

PMID- 24924019
TI  - Does the evolutionary perspective offer more than constraints?

PMID- 24924020
TI  - Choosing a unifying theory for cognitive development.

PMID- 24924021
TI  - Problem spaces, language and connectionism: Issues for cognition.

PMID- 24924022
TI  - Unified theories and theories that mimic each other's predictions.

PMID- 24924023
TI  - On models and mechanisms.

PMID- 24924024
TI  - A cognitive process shell.

PMID- 24924025
TI  - On putting the cart before the horse: Taking perception seriously in unified
      theories of cognition.

PMID- 24924026
TI  - Cognition and simulation.

PMID- 24924027
TI  - Cartesian vs. Newtonian research strategies for cognitive science.

PMID- 24924028
TI  - A psychobiological theory of attachment.
AB  - This article describes a neurobiological basis for the "first attachment" of the
      primate infant to its caretaker. The infant normally internalizes a
      neurobiological "image" of the behavioral and emotional characteristics of its
      caregiver that later regulates important features of its brain function. Current
      models of sensorimotor analysis and its relation to emotion suggest that
      sensorimotor systems are also habit and memory systems, their functional status
      and lability regulated in part by biogenic amine systems. The intertwined
      development of neural and social functions can sometimes go awry. If the
      attachment process fails or the caregiver is incompetent, the infant may become
      socially dysfunctional. This helps explain the developmental psychopathology and
      later vulnerability to adult psychopathology that result from disruptions of
      social attachment. 

PMID- 24924029
TI  - Refining the attachment model.

PMID- 24924030
TI  - What do attachment objects afford?

PMID- 24924031
TI  - Levels of explanation in theories of infant attachment.

PMID- 24924032
TI  - A wise child: Face perception by human neonates.

PMID- 24924034
TI  - Oxytocin and the neurobiology of attachment.

PMID- 24924033
TI  - The many levels of attachment.

PMID- 24924035
TI  - Attachment: How early, how far?

PMID- 24924036
TI  - The meanings of attachment.

PMID- 24924037
TI  - Attachment and the sources of behavioral pathology.

PMID- 24924038
TI  - Does function imply structure?

PMID- 24924039
TI  - A new psychobiological theory of attachment: Primum non nocere.

PMID- 24924040
TI  - Attachment: A view from evolutionary biology and behavior genetics.

PMID- 24924041
TI  - Behavioural, aminergic and neural systems in attachment.

PMID- 24924042
TI  - The interface between the psychobiological and cognitive models of attachment.

PMID- 24924043
TI  - A psychopharmacologist's view of attachment.

PMID- 24924044
TI  - Emotions of human infants and mothers and development of the brain.

PMID- 24924045
TI  - Psychophysical scaling: Judgments of attributes or objects?
AB  - Psychophysical scaling models of the form R = f(I), with R the response and I
      some intensity of an attribute, all assume that people judge the amounts of an
      attribute. With simple biases excepted, most also assume that judgments are
      independent of space, time, and features of the situation other than the one
      being judged. Many data support these ideas: Magnitude estimations of brightness
      (R) increase with luminance (I). Nevertheless, I argue that the general model is
      wrong. The stabilized retinal image literature shows that nothing is seen if
      light does not change over time. The classification literature shows that
      dimensions often combine to produce emergent properties that cannot be described
      by the elements in the stimulus. These and other effects cannot be adjusted for
      by simply adding variables to the general model because some factors do not
      combine linearly. The proposed alternative is that people initially judge the
      entire stimulus - the object in terms of its environment. This agrees with the
      constancy literature that shows that objects and their attributes are identified
      through their relations to other aspects of the scene. That the environment
      determines judgments is masked in scaling studies where the standard procedure is
      to hold context constant. In a typical brightness study (where different lights
      are presented on the same background on different trials) the essential stimulus
      might be the intensity of the light or a difference between the light and the
      background. The two are perfectly confounded. This issue is examined in the case
      of audition. Judgments of the loudness of a tone depend on how much that tone
      differs from the previous tone in both pitch and loudness. To judge loudness (and
      other attributes) people first seem to process the stimulus object in terms of
      differences between it and other aspects in the situation; only then do they
      assess the feature of interest. Psychophysical judgments will therefore be better
      interpreted by theories of attention that are based in biology or psychology than
      those (following Fechner) that are based in classical physics. 

PMID- 24924046
TI  - Perception, apperception and psychophysics.

PMID- 24924047
TI  - Integration psychophysics is not traditional psychophysics.

PMID- 24924048
TI  - Lockhead's view of scaling: Something's fishy here.

PMID- 24924049
TI  - Psychophysical scaling within an information processing approach?

PMID- 24924050
TI  - Psychophysical scaling: To describe relations or to uncover a law?

PMID- 24924051
TI  - Accounting for an old inconsistency in the psychophysics of Plateau and Delboeuf.

PMID- 24924052
TI  - Psychophysical scaling: Context and illusion.

PMID- 24924053
TI  - The determinants of perceived brightness are complicated, but not hopelessly so.

PMID- 24924054
TI  - Can brightness be related to luminance by a meaningful function?

PMID- 24924055
TI  - Psychophysical invariance, perceptual invariance and the physicalistic trap.

PMID- 24924056
TI  - The complexity and importance of the psychophysical scaling of sensory
      attributes.

PMID- 24924057
TI  - Scales falling from the eyes?

PMID- 24924058
TI  - Walking in a psychophysical dustbowl creates a dustcloud.

PMID- 24924059
TI  - Psychophysics: Plus ca change ....

PMID- 24924060
TI  - Context effects: Pervasiveness and analysis.

PMID- 24924061
TI  - Will the real stimulus please step forward?

PMID- 24924062
TI  - Two categories of contextual variable in perception.

PMID- 24924063
TI  - Covert converging operations for multidimensional psychophysics.

PMID- 24924064
TI  - The perplexing plurality of psychophysical processes.

PMID- 24924065
TI  - Psychophysics and quantitative perceptual laws.

PMID- 24924066
TI  - How important are dimensions to perception?

PMID- 24924067
TI  - Attributes or objects: A paradigm shift in psychophysics.

PMID- 24924068
TI  - The evident object of inquiry.

PMID- 24924069
TI  - Context effects in the entropic theory of perception.

PMID- 24924070
TI  - Should the psychophysical model be rejected?

PMID- 24924071
TI  - Selecting one attribute for judgment is not an act of stupidity.

PMID- 24924072
TI  - Do we scale "objects" or isolated sensory dimensions?

PMID- 24924073
TI  - Ceteris paribus laws.

PMID- 24924074
TI  - Keeping the bath water along with the baby: Context effects represent a
      challenge, not a mortal wound, to the body of psychophysics.

PMID- 24924076
TI  - Corrigenda.

PMID- 24924075
TI  - Relation of sensory scales to physical scales.

PMID- 24924077
TI  - An ethopharmacological analysis of morphine effects in fish (Macropodus
      Opercularis).
AB  - The behavioural effects of morphine on fish (Macropodus opercularis) were studied
      by an ethopharmacological analysis. For this purpose active and passive
      behavioural units were observed. The results show that morphine treatment had a
      stimulating effect. However, the treatment resulted not in a general enhancement
      of active behavioural units, but in a selective increase of some of them, such as
      swimming and erratic behaviour, or in stereotyped behaviours, such as circling.
      By contrast, high dosages of morphine resulted in a decrease of escape and of
      standing under the surface behaviours. 

PMID- 24924078
TI  - Role of the pituitary-adrenocortical axis in the control of agonistic behaviour
      after single and repeated footshock in castrated male mice.
AB  - Two experiments were conducted to examine the role of the pituitary
      adrenocortical axis in the mediation of the effects of single and repeated
      electric footshock on subsequent agonistic responding in castrated male mice. It
      was found that (1) preventing corticosterone responses to shock occludes the
      facilitatory effects of single shock on both aggressive and submissive behaviour
      and occludes the additional increases in submissive behaviour which normally
      occur after repeated shock, and (2) blocking pituitary release of ACTH by
      dexamethasone treatment restores aggressive behaviour after repeated shock,
      independently of the initial levels of corticosterone and testosterone. These
      findings suggest that (1) increases in aggressive and submissive behaviour in
      response to single shock depend on shock-induced increases in corticosterone
      levels; (2) further increases in submissive behaviour in response to repeated
      shock require further increases in the corticosterone levels; and (3) inhibition
      of aggressive behaviour after shock repetition appears to depend on increases in
      ACTH levels, and occurs independently of the initial corticosterone and
      testosterone levels. 

PMID- 24924080
TI  - Response to heiner.

PMID- 24924079
TI  - A problem with using derivatives to explain the matching law.
AB  - Herrnstein (1979) recently claimed that the matching law could be derived from an
      ordinary differential equation. He failed, however, to analyze the dynamic
      properties of his proposed equation. I show that it implies behavior cannot
      stabilize in accordance with the matching law. Consequently, Herrnstein's
      equation cannot explain why matching behavior has been widely observed. 

PMID- 24924081
TI  - Spontaneous and deferred imitation in the pigeon.
AB  - Experimentally-naive pigeons were placed on one side of a clear partition. A
      pigeon on the other side received food for pecking a ping-pong ball, pulling a
      rope, or pecking a plastic disk. When given access to a similar object, each
      naive pigeon pecked or pulled at a low rate for several sessions and two
      continued to do so forseveral sessions in the absence of the leader. In a second
      experiment, the latter effect was demonstrated after a delay of 24 hours, even
      though the naive pigeons had never had access to the object in the presence of
      the model. A third experiment demonstrated that the effect on the follower was
      not due merely to the presence of or activity of another pigeon and was at least
      somewhat specific to the behavior of the model. 

PMID- 24924082
TI  - Saline intake after shifts to water in hamsters and gerbils.
AB  - In Experiment 1, hamsters and gerbils were given a 24-hr two-bottle test with
      saline and water for eight days before being placed on a water-only condition for
      the subsequent four days. On day 13 the saline bottle was returned to the animals
      and their intake of saline and water was monitored for another six days.
      Comparisons were made of the animals' intake of saline during the last two pre
      withdrawal with that during the first two post-withdrawal days. Saline intake was
      enhanced in male but not in female gerbils following the 4-day withdrawal period.
      In contrast, male hamsters showed a decrement in their saline intake while female
      hamsters showed no significant change in these pre- and post-withdrawal measures.
      In Experiment 2, a between-groups design was used to test for differences between
      the saline intake of hamsters and gerbils exposed to the experimental (saline
      withdrawal) and control (no withdrawal) conditions. When tested with 0.45% or
      2.0% saline solution, there was no significant difference between experimental
      and control hamsters. The results with male gerbils indicated a significant
      withdrawal effect when the animals were tested with 3.0% saline but not with 4.0%
      NaCl solution. The implications of these results for a behavioral taxonomy of
      "compensators" and "noncompensators" are discussed. 

PMID- 24924083
TI  - Modification of nocturnal spontaneous and adrenergic-induced feeding in the rat
      following either A5 or A7 lesions.
AB  - The ingestive profiles of intact, A5 and A7 damaged animals were examined during
      the 2-hr nocturnal period following onset of the dark cycle. A5, A7 and intact
      rats consumed comparable amounts of food following initial access to food
      nocturnally. Sebsequent feeding declined in A5 animals below control values and
      failed to return to baseline at the end of the nocturnal period examined. A7
      damaged rats appeared more resistant to the appetite suppressing effects of
      initial meal taking and consumed more food than control animals. Only A5 damaged
      rats were noted to be hyperdipsic during the immediate 10 postoperative days.
      Intracranial injection of 1-norepinephrine bitartrate (10 ug/ul) into the
      paraventricular nucleus (PVN) of the hypothalmus produced a reliable facilitation
      of feeding in A5, A7 and intact rats during the first hour of the dark cycle. A5
      rats exhibited the largest increase in feeding elicited by NE administration into
      the PVN. This feeding response was observed in rats with A5 lesions regardless of
      whether testing was carried out during the initial hours of the dark cycle or
      during a predetermined "satiation" test. A5 lesions also effected a marked
      hyperglycemia while A7 lesions were ineffective in this respect. Taken together
      these data suggest the A5 and A7 cell groupings regulate spontaneous feeding
      within a rostrally coursing feeding circuitry and appear to interact with the PVN
      in the elicitation of noradrenergic feeding. 

PMID- 24924084
TI  - Hypotheses on mechanisms underlying observational learning in animals.
AB  - Learning through observation or vicarious learning has been systematically
      studied in a variety of animal species for only 20 years. Demonstrating in
      animals a capacity to benefit from a conspecific's experience, this type of
      acquisition was first thought to require superior cognitive processes and thus to
      be restricted to primates, if possible at all in animals. The concept of
      imitation was commonly applied in this line of study to any social transmission.
      Later, experiments on vicarious learning showed that numerous species (rodents,
      cats, birds, primates, etc.) learn more quickly to perform an act whenever they
      have the opportunity of watching a conspecific performing that act. The principal
      characteristic of this acquisition is that it occurs during the observation
      period when the observer has no opportunity of either performing a response or
      receiving reinforcement. Four hypothesis have been put forward to explain the
      mechanisms underlying this type of acquisition : local enhancement, the
      opportunity for mediate responses, a sensory preconditioning, and the monitoring
      of the observer's response by some quantitative and/or qualitative aspects of the
      model's response. The fact that animals prove to have such a capacity is moreover
      a factor to be kept in mind in all studies in the eco-ethological field
      (particularly those concerning the predator-prey relation). 

PMID- 24924085
TI  - The ontogeny of feeding behaviour in four species of centrarchid fish.
AB  - Relatively little work has been done on the ontogeny of feeding behaviour in
      fish. One of the aims of this study was to compare the ontogeny of feeding
      behaviour in four species of centrarchid fish of diverse feeding guilds. A second
      aim was to test Mayr's hypothesis that the locomotory acts involved in the
      ontogeny of feeding behaviour would be stereotyped. All four species initially
      displayed five feeding acts, with three of the acts disappearing from the
      repertoire at various intervals. The disappearance of the acts appeared to be
      related to the size and not to the age of the fry. The acts decreased in
      frequency as the fry aged and differences among the species in frequencies were
      minimal. The data supported Mayr's hypothesis but a modifying corollary was added
      to account for changes due to maturation. 

PMID- 24924086
TI  - Variability of force and interresponse time under random interval reinforcement
      schedules.
AB  - Response variability was examined under five random interval schedules with
      minimum mean interreinforcement intervals of 15, 30, 60, 120, and 240 sec.
      Distributions of response force-time integrals showed no systematic variability
      changes with increases in reinforcement intermittency. Corresponding
      distributions of interresponse times revealed increases in variability
      accompanying increases in reinforcement intermittency. The relationship of
      variability to these two measures, and the potential effect of behavior outside
      the experimentally measured response class, on recorded variability within the
      class, are considered. 

PMID- 24924087
TI  - Overshadowing of responding on ratio and interval schedules by an independent
      predictor of reinforcement.
AB  - This experiment replicated previous demonstrations that interposing a brief
      stimulus between reinforced responses and the presentation of the reinforcer
      reduces responding maintained by intermittent reinforcement schedules.
      Furthermore, we could find no significant difference between the relative size of
      the reduction during training on ratio and interval schedules when the predictive
      significance of the response and stimulus was controlled by a yoking procedure. 

PMID- 24924088
TI  - The influence of sex, sexual condition and age on the exploratory behaviour of
      wild wood mice (Apodemus Sylvaticus L.).
AB  - From April 1978 to April 1980 the exploratory behaviour of more than 1000 wild
      wood mice was studied in a modified open field test situation. The influence of
      sex, sexual condition and age on the exploratory activity was investigated.
      Sufficient data being available, the exploratory activity of both sexually active
      and sexually inactive adult males and adult females, of both sexually active and
      sexually inactive subadult males and subadult females and of both sexually
      inactive juvenile males and females was compared by means of a one way analysis
      of variance for each two-month period. In other analyses the influence of age of
      adult males and adult females on the exploratory behaviour was further examined.
      No differences could be found in the exploratory activity displayed by males or
      females and by sexually active or sexually inactive animals. Also a clear
      influence of age was absent. The interindividual variation was very large. 

PMID- 24924089
TI  - The putative role of vitamin D in essential hypertension: stepping into the
      light?

PMID- 24924090
TI  - Response to "The putative role of vitamin D in essential hypertension: stepping
      into the light?".

PMID- 24924091
TI  - Aerobic exercise and endothelial function in pre- and postmenopausal women.

PMID- 24924092
TI  - Response to "Aerobic exercise and endothelial function in pre- and post
      menopausal women".

PMID- 24924096
TI  - Molecular weight dependent vertical composition profiles of PCDTBT:PC71BM blends
      for organic photovoltaics.
AB  - We have used Soxhlet solvent purification to fractionate a broad molecular weight
      distribution of the polycarbazole polymer PCDTBT into three lower polydispersity
      molecular weight fractions. Organic photovoltaic devices were made using a blend
      of the fullerene acceptor PC71BM with the molecular weight fractions. An average
      power conversion efficiency of 5.89% (peak efficiency of 6.15%) was measured for
      PCDTBT blend devices with a number average molecular weight of Mn = 25.5 kDa.
      There was significant variation between the molecular weight fractions with low
      (Mn = 15.0 kDa) and high (Mn = 34.9 kDa) fractions producing devices with average
      efficiencies of 5.02% and 3.70% respectively. Neutron reflectivity measurements
      on these polymer:PC71BM blend layers showed that larger molecular weights leads
      to an increase in the polymer enrichment layer thickness at the anode interface,
      this improves efficiency up to a limiting point where the polymer solubility
      causes a reduction of the PCDTBT concentration in the active layer.

PMID- 24924097
TI  - [Squamous cell carcinomas of the ear: factors of gravity and surgical treatment,
      about 30 cases].
AB  - INTRODUCTION: Squamous cell carcinomas (SCC) of the ear are known for their
      aggressiveness. The aim of this study was to investigate factors of gravity while
      freeing the therapeutic requirements. PATIENTS AND METHODS: This is a
      retrospective study of 28 patients (30 ears) operated for SCC. The
      characteristics of the lesion, the presence of metastasis, treatment modalities
      and histologic findings were collected. Local recurrences and metastasis are
      identified with a mean follow-up time of 37months (17-110months). RESULTS: The
      lesion size was less than 2cm in 19 cases (63.3%) and greater than or equal to
      2cm in 11 cases (36.7%). Macroscopic resection margins were 5, 7 or 10mm. The
      resections were histologically incomplete in 4 cases (13%) requiring further
      surgery. Six cases had local recurrence (20%): three with pulmonary or lymph node
      metastases (10%) and one death (3.3%). In these 6 cases of recurrence, the
      surgical margins were 6.3mm on average, the initial lesion measured always
      greater than 2cm (100%). Three quarters of incomplete resections have recurrent
      despite a surgical revision in healthy margin. CONCLUSION: Our study confirms the
      data of literature, namely the pejorative character of a lesion greater than 2cm
      and incomplete resection. The HAS recommendations seem minimal regarding the ear.
      In case of injury by more than 2cm and with a proximal location on the ear pinna,
      only amputation of the ear allows satisfactory cancer control.

PMID- 24924098
TI  - Gilthead seabream (Sparus aurata) immune responses are modulated after feeding
      with purified antinutrients.
AB  - The present study aimed to evaluate the effects of two purified antinutrients,
      soy saponins and phytosterols, in an important species for Mediterranean
      aquaculture. For this purpose, gilthead seabream (Sparus aurata) were fed six
      experimental diets containing two levels of those antinutrients, alone or in
      combination, and a control diet, to apparent visual satiation under controlled
      conditions. Blood and head-kidney were collected at 7, 15 and 48 days following
      first feeding in order to assess immune parameters and the expression of immune
      related genes. Plasma bactericidal and alternative complement pathway activities
      increased in fish fed antinutrients compared to fish fed the control diet during
      the course of the experiment, with more important changes at 7 and 48 days for
      bactericidal activity and at 7 and 15 days for complement values. In contrast,
      plasma total immunoglobulins (Ig) increased in fish fed antinutrients only at 48
      days. Caspase 1 (casp1), interleukin 18 (il18), colony-stimulating factor-1
      receptor (csfr) and hepcidin (hep) presented similar patterns of expression with
      more important changes at 7 and 48 days, while interleukin 10 (il10) and beta
      defensin (def) were mainly up-regulated in fish fed antinutrients at 48 days. The
      level of expression of IgM increased already at 7 days in fish fed the low
      concentration of both saponins and phytosterols while a general up-regulation was
      observed at 48 days compared to fish fed the control diet. Results suggest that
      feeding seabream a diet with purified saponins and phytosterols, alone or in
      combination, induces a number of changes that are related to the development of
      inflammation, with most important changes in fish fed the lower phytosterols
      concentration. 

PMID- 24924099
TI  - Reliable determination of training-induced alterations in muscle fiber
      composition in human skeletal muscle using quantitative polymerase chain
      reaction.
AB  - Determination of muscle fiber composition in human skeletal muscle biopsies is
      often performed using immunohistochemistry, a method that tends to be both time
      consuming, technically challenging, and complicated by limited availability of
      tissue. Here, we introduce quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR)-based Gene-family profiling (GeneFam) of myosin heavy chain
      (MyHC) mRNA expression as a high-throughput, sensitive, and reliable alternative.
      We show that GeneFam and immunohistochemistry result in similar disclosures of
      alterations in muscle fiber composition in biopsies from musculus vastus
      lateralis and musculus biceps brachii of previously untrained young women after
      12 weeks of progressive strength training. The adaptations were evident as (a)
      consistent increases in MyHC2A abundance; (b) consistent decreases in MyHC2X
      abundance; and (c) consistently stable MyHC1 abundance, and were not found using
      traditional reference gene-based qRT-PCR analyses. Furthermore, muscle fiber
      composition found using each of the two approaches was correlated with each other
      (r = 0.50, 0.74, and 0.78 for MyHC1, A, and X, respectively), suggesting that
      GeneFam may be suitable for ranking of individual muscle phenotype, particularly
      for MyHC2 fibers. In summary, GeneFam of MyHC mRNA resulted in reliable
      assessment of alterations in muscle fiber composition in skeletal muscle of
      previously untrained women after 12 weeks of strength training. 

PMID- 24924101
TI  - Recent patents on novel MCH1 receptor antagonists as potential anti-obesity
      drugs.
AB  - Today, the 'obesity pandemic' is one of the biggest health issues around the
      world. Melanin-concentrating hormone (MCH), a hypothalamic neuropeptide, is one
      of the most potent, central stimulators of feeding and it also attenuates energy
      expenditure. Inhibitions of the MCH receptor, the melanin-concentrating hormone
      receptor-1 (MCHR1), has attracted considerable attention as a potential anti
      obesity drug, during the last decade. Now, there are a large number of MCHR1
      antagonists, pharmacological tools and clinical drug candidates that can provide
      clues to develop new structures with high potency and good pharmacokinetic
      profile. The function of MCHR1 in energy homeostasis, obesity, metabolic
      syndrome, mood disorders and inflammatory bowel disease is discussed. Relevant
      clinical trials and patent background information of the MCHR1 antagonists over
      the last 4 years are also reviewed. 

PMID- 24924102
TI  - Possible physiopathological roles of the transglutaminase activity in the
      etiopathogenesis of human neurodegenerative diseases.
AB  - Transglutaminases are ubiquitous enzymes which catalyze post-translational
      modifications of proteins. The main activity of these enzymes is the cross
      linking of glutaminyl residues of a protein/peptide substrate to lysyl residues
      of a protein/peptide co-substrate. In addition to lysyl residues, other second
      nucleophilic co-substrates may include monoamines or polyamines (to form mono- or
      bi-substituted /crosslinked adducts) or -OH groups (to form ester linkages). In
      the absence of co-substrates, the nucleophile may be water, resulting in the net
      deamidation of the glutaminyl residue. Transglutaminase activity has been
      suggested to be involved in molecular mechanisms responsible for both
      physiological or pathological processes. For example, neurodegenerative diseases,
      such as Alzheimer's Disease, Parkinson's Disease, supranuclear palsy,
      Huntington's Disease and other polyglutamine diseases, are characterized in part
      by aberrant cerebral transglutaminase activity and by increased cross-linked
      proteins in affected brains. This review focuses on the possible molecular
      mechanisms responsible for such diseases and on the possible therapeutic effects
      of transglutaminase inhibitors for patients with diseases characterized by
      aberrant transglutaminase activity. 

PMID- 24924100
TI  - Social insecurity in relation to orbitofrontal activity in patients with eating
      disorders: a near-infrared spectroscopy study.
AB  - BACKGROUND: Functional neuroimaging techniques are widely used to elucidate
      changes in brain activity, and various questionnaires are used to investigate
      psychopathological features in patients with eating disorders (ED). It is well
      known that social skills and interpersonal difficulties are strongly associated
      with the psychopathology of patients with ED. However, few studies have examined
      the association between brain activity and social relationships in patients with
      ED, particularly in patients with extremely low body weight. METHODS: In this
      study, 22-channel near-infrared spectroscopy was used to quantify regional
      hemodynamic changes during a letter fluency task (LFT) in 20 female patients with
      ED with a mean body mass index of 14.0 kg/m(2) and 31 female controls (CTLs).
      Symptoms were assessed using the Eating Disorder Inventory-2 and Beck Depression
      Inventory. We hypothesized that frontal activity in patients with ED would be
      lower than in CTLs and would show different correlations with psychopathological
      features compared with CTLs. RESULTS: The LFT performance and score on the social
      insecurity subscale of the Eating Disorder Inventory-2 were significantly higher
      in the ED group than in the CTL group. The mean change in oxygenated hemoglobin
      (oxy-Hb) in bilateral frontal regions during the LFT was significantly smaller in
      the ED group than in the CTL group. Social insecurity score was positively
      correlated with the concentration of oxy-Hb in the bilateral orbitofrontal cortex
      in the ED group but not in the CTL group. CONCLUSIONS: These results suggest that
      activity of the orbitofrontal cortex is associated with social insecurity and
      disturbed in patients with ED. Therefore, disturbed orbitofrontal cortex activity
      may underlie the lack of insight and social isolation that is characteristic of
      patients with ED.

PMID- 24924103
TI  - New General Medical Council language checks to be introduced in the summer. How
      will radiology reports fare?

PMID- 24924104
TI  - [Presentation of primary thyroid tuberculosis as a sub-acute thyroid abscess. A
      case report].

PMID- 24924105
TI  - [Not Available].
AB  - One of the most striking features of cave fishes is their pronounced ocular
      regression. They are, however, perfectly adapted since they multiply and display
      the behaviour patterns which are biologically important in their surroundings. It
      is therefore of interest to study the relative role of visual factors in the
      corresponding behaviour patterns in related epigean species. Other authors have
      previously demonstrated the dominant role of chemical stimuli in the releasing of
      sexual behaviour patterns in M. sphenops, of which some forms are cavernicolous.
      In M. velifera and M. latipinna, on the contrary, visual factors seem more
      important. The releasers of the aggressive behaviour patterns of these three
      species seem to be predominantly visual. In the present study, the importance of
      visual factors has been verified experimentally in M. velifera by comparing the
      observed behavioural differences in experimentally blinded individuals and normal
      controls. The results of the pre-experimental phase show that there is no
      difference between these two groups before blinding, neither in the frequency of
      the patterns, nor in their numerical values. The results of the first
      experimental phase confirm the importance of visual releasers in the sexual
      behaviour patterns of M. velifera. Thus, sexual approaches, mouth-abdomen
      contacts and copulation attempts are totally absent in blinded pairs. Sexual
      motivation however is still present since the gonopodal flexions are equally
      frequent in both groups. On the other hand, it seems that aggressive behaviour
      patterns are maintained in blinded individuals but only when the partners are
      very close to each other or when an actual contact has taken place. The
      comparison of pairs in which only one of the partners is blinded (second
      experimental phase), as well as results of the first phase, suggest that
      experimental blinding does not cause hormonal changes liable to influence the
      observed patterns. In addition to this, the role of the ? in courtship has been
      specified. When a ? individual is intact and receptive, it will initiate
      courtship when it is placed in the company of an inactive blinded partner. 

PMID- 24924106
TI  - The response of willow grouse chicks to auditory stimuli 1. Preference for hen
      grouse calls.
AB  - Willow grouse (Lagopus lagopus lagopus) chicks newly hatched from mechanically
      incubated eggs were exposed to different combinations of sounds in a heated
      runway. They approached a loudspeaker playing grouse hen calls, which they had
      never heard, in preference to one playing the noise of the hatching machine from
      which they had just been removed. Similarly they preferred the hen call to
      another novel sound. When the three sounds were played singly instead of in
      pairs, only the hen call was approached. 

PMID- 24924107
TI  - Catecholamine levels in whole brain of stressed and control domestic and wild
      rats (Rattus Norvegicus).
AB  - Whole brain catecholamine (dopamine, nonadrenaline, adrenaline) levels were
      measured in control and electric footshocked Wild and domestic (Sprague Dawley
      and Long Evans) rats. No significant differences were found among the three
      strains of rats for combined total catecholamine content, or for combined total
      catecholamines between the control and footshocked groups. Significant
      differences were found for the total of each catecholamine taken separately,
      dopamine being present at three times the level of noradrenaline and ten times
      the level of adrenaline. No significant differences were found for dopamine in
      both control and footshocked animals among all three rat strains. Noradrenaline
      was significantly higher in the control domestic rats compared to the control
      Wild rats, and in the footshocked domestic rats compared to the footshocked Wild
      rats. No differences in noradrenaline levels were found between Sprague Dawley
      and Long Evans rats, but noradrenaline increased significantly in the latter
      following footshock. Adrenaline was significantly highest in the Sprague Dawley
      controls and lowest in the Wild controls. Footshocking resulted in almost
      identical levels of adrenaline in the domestic strains and an increase in the F1
      Wild strain. 

PMID- 24924108
TI  - Influence of environmental disturbances on uterine motility during pregnancy and
      parturition in rabbit and sheep.
AB  - The effect of stressful stimuli on uterine motility during pregnancy and
      parturition was studied in sheep and rabbits. The effects of epinephrine and
      various alpha- and beta- adrenergic blocking agents were also investigated. By
      comparing the results of these experiments, the authors conclude that the
      increase in epinephrine level (stress response of the organism) is the direct
      cause of the observed changes in uterine motility. Both stress and epinephrine
      caused either an activation or an inhibition of uterine motility. The direction
      of the effect depended on the ratio of sex-steroid concentrations in the plasma.
      Blood plasma levels of oestradiol-17beta and of progesterone were determined in
      the sheep. Both stress and epinephrine inhibited uterine motility only when
      plasma levels of oestradiol-17beta were very high (oestrogen-domination). The
      biological relevance and clinical implications are discussed. 

PMID- 24924109
TI  - Responsiveness to "social" releasers in cattle. I. A study of the differential
      and additive effects of visual and sound stimuli, with special reference to the
      law of heterogeneous summation.
AB  - Two experiments (Exp.1, Exp.2) were carried out to investigate the effects of
      social releasers, i.e. models and calls of conspecifics, on the approach
      responses of Friesian-Dutch heifers. In Exp.1, models consisted of either a vague
      representation of a conspecific's shape, or of a life-sized photograph of a
      conspecific. Sound (S) stimulations (calls) and movement (M) were combined to
      these visual (V) models. In Exp.2, V models and S stimulations were presented
      either separately or in combination. Models consisted of a ? and of a ? life
      sized photograph and S stimulations consisted of recorded calls of ?? or of ??
      conspecifics. In Exp.1, a significant increase in responsiveness was found after
      addition of sound S to the V models, especially to the photographs. Adding S to V
      models resulted in a much higher increase in responsiveness than adding M to V
      models. An additive effect was also found in Exp.2: combined presentations of V
      and S increased significantly the number of responses and of responding subjects
      as compared to either V or S separate presentations. In both Exp.1 and Exp.2, the
      total number of responses was a little more than twice as high for combined
      presentation of V and S as it was for V separate presentations, or for S separate
      presentations (Exp.2). In Exp.2, a complete verification of Seitz's law of
      heterogeneous summation of the stimuli was attempted by a further comparison,
      demonstrating that the releasing effect of V and S presented in combination
      (simultaneously) was equivalent to the number of responses found after addition
      of the partial effects of V and S presented separately (successively). 

PMID- 24924111
TI  - Abecedarium: Who am I? T'....

PMID- 24924112
TI  - Sudden bilateral hearing loss revealing polyarteritis nodosa.

PMID- 24924113
TI  - Hearing screening by community physicians in under-2 year-olds.
AB  - The efficacy of neonatal screening in lowering age at diagnosis and treatment in
      congenital hearing loss should not mask the limitations due to the fact that
      hearing loss often appears or is detected after birth. Early diagnosis of
      secondary or progressive postnatal hearing loss is nevertheless necessary and
      justifies systematic screening of hearing disorder in all children seen in
      consultation, for whatever reason. Screening bilateral hearing loss in under-2
      year-olds in a community context is feasible, using simple means: parent
      interview, clinical observation, and acoumetry using the voice and sound-emitting
      toys. In case of abnormality detected or suspected on screening, children of
      whatever age should be referred to an ENT specialist for complete audiometric
      assessment. Behavioural audiometry is feasible in very young children, and
      indispensable to diagnosis. The parents will only be reassured after specialized
      hearing examinations have been performed. 

PMID- 24924115
TI  - Abecedarium: Who am I? S'....

PMID- 24924114
TI  - Dysphagia after radiotherapy: state of the art and prevention.
AB  - Adjuvant radiotherapy after surgery or exclusive radiotherapy, with or without
      concurrent chemotherapy is a valuable treatment option in the great majority of
      patients with head and neck cancer. Recent technical progress in radiotherapy has
      resulted in a decreased incidence of xerostomia. Another common toxicity of
      radiotherapy is dysphagia, which alters the nutritional status and quality of
      life of patients in remission. The objective of this review is to describe the
      physiology of swallowing function, the pathophysiology of radiation-induced
      dysphagia and the various strategies currently available to prevent this
      complication. 

PMID- 24924116
TI  - Abecedarium: Who am I? R' ....

PMID- 24924118
TI  - Detection of glutamate and acetylcholine with organic electrochemical transistors
      based on conducting polymer/platinum nanoparticle composites.
AB  - The aim of the study is to open a new scope for organic electrochemical
      transistors based on PEDOT:PSS, a material blend known for its stability and
      reliability. These devices can leverage molecular electrocatalysis by
      incorporating small amounts of nano-catalyst during the transistor manufacturing
      (spin coating). This methodology is very simple to implement using the know-how
      of nanochemistry and results in efficient enzymatic activity transduction, in
      this case utilizing choline oxidase and glutamate oxidase. 

PMID- 24924117
TI  - Comparison of early hearing outcomes of type 2 ossiculoplasty using
      hydroxyapatite bone cement versus other materials.
AB  - OBJECTIVES: To compare the hearing outcomes of type 2 ossiculoplasties for
      erosion of the long process of the incus according to the reconstruction material
      used: cartilage, ossicles, hydroxyapatite (HAP) partial ossiculoplasty
      reconstruction prostheses (PORP), titanium PORP, and HAP cement. Complications
      related to cement reconstruction were systematically investigated and reported.
      MATERIAL AND METHODS: Seventy patients operated between 2007 and 2011 for non
      cholesteatomatous chronic otitis media were included in this study. Mean air-bone
      gap (500, 1000, 2000 and 4000Hz) was compared preoperatively and 3 months
      postoperatively according to the reconstruction material used. Postoperative
      results were classified as good (air-bone gap<10dB), acceptable (air-bone gap 10
      20dB) or insufficient (air-bone gap>20dB) and were compared according to the
      reconstruction material used. RESULTS: Groups were comparable in terms of
      preoperative air-bone gap (P>0.05, Anova). The mean postoperative air-bone gap
      was 14.82+/-11.52dB in the cartilage group, 13.31+/-9.03dB in the ossicles group,
      22.12+/-11.95dB in the HAP PORP group, 13.75+/-11.20dB in the titanium PORP
      group, and 7.26+/-8.99dB in the HAP cement group. Statistical analysis showed a
      significant air-bone gap difference only between HAP PORP and HAP cement groups
      (P=0.021, Tukey's test). No significant difference was observed between groups
      when classified by air-bone gap class (P=0.29, Fisher's test). No major
      complication was reported with HAP cement with a minimum follow-up of 10 months.
      CONCLUSION: HAP cement provides similar hearing outcomes to autologous material
      and titanium PORP, and better outcomes than HAP PORP in our patients. These
      results must be confirmed in a larger series with a longer follow-up.

PMID- 24924119
TI  - EMA policy on transparency is "strikingly" similar to deal struck with drug
      company, say experts.

PMID- 24924121
TI  - Activation of benign autoimmunity as both tumor and autoimmune disease
      immunotherapy: a comprehensive review.
AB  - Here, I consider how benign autoimmunity, the immunological homunculus, can be
      used to reinstate the healthy regulation of inflammation in both autoimmune
      diseases and in tumor immunotherapy. Different autoimmune diseases manifest
      clinically distinct phenotypes, but, in general, they all result from the
      transition of benign, healthy recognition of key body molecules into a damaging
      effector reaction. Tumors, in contrast to autoimmune diseases, grow by subverting
      the immune system into supporting and protecting the growing tumor from immune
      surveillance. Therefore our therapeutic aim in autoimmune disease is to induce
      the immune system to down-regulate the specific autoimmune effector reaction that
      causes the disease; in tumor immunotherapy, on the contrary, we aim to deprive
      the growing tumor of its illicit activation of immune suppression and to unleash
      an autoimmune disease targeted to the tumor. The recent success of anti-PD1 and
      anti-CTLR4 treatments exemplify the reinstatement of tumor autoimmunity
      subsequent to inhibition of immune suppression. With regard to the therapy of
      autoimmune diseases, I cite examples of immune system down-regulation of
      autoimmune diseases by T cell vaccination or HSP60 peptide treatment. Inducing
      the immune system to regulate itself is safer than global immune suppression and
      may be more effective in the long run. 

PMID- 24924120
TI  - Cytokine networks that mediate epithelial cell-macrophage crosstalk in the
      mammary gland: implications for development and cancer.
AB  - Dynamic interactions between the hormone responsive mammary gland epithelium and
      surrounding stromal macrophage populations are critical for normal development
      and function of the mammary gland. Macrophages are versatile cells capable of
      diverse roles in mammary gland development and maintenance of homeostasis, and
      their function is highly dependent on signals within the local cytokine
      microenvironment. The mammary epithelium secretes a number of cytokines,
      including colony stimulating factor 1 (CSF1), transforming growth factor beta 1
      (TGFB1), and chemokine ligand 2 (CCL2) that affect the abundance, phenotype and
      function of macrophages. However, aberrations in these interactions have been
      found to increase the risk of tumour formation, and utilisation of stromal
      macrophage support by tumours can increase the invasive and metastatic potential
      of the cancer. Studies utilising genetically modified mouse models have shed
      light on the significance of epithelial cell-macrophage crosstalk, and the
      cytokines that mediate this communication, in mammary gland development and
      tumourigenesis. This article reviews the current status of our understanding of
      the roles of epithelial cell-derived cytokines in mammary gland development and
      cancer, with a focus on the crosstalk between epithelial cells and the local
      macrophage population. 

PMID- 24924122
TI  - The non-canonical Wnt ligand, Wnt5a, is upregulated and associated with
      epithelial to mesenchymal transition in epithelial ovarian cancer.
AB  - OBJECTIVE: Aberrant Wnt signalling has previously been associated with
      gynaecological cancers, and the aim of this study was to investigate the
      expression of Wnt5a in epithelial ovarian cancer, and clarify its role in
      activating or inhibiting beta-catenin dependent and independent Wnt signalling
      pathways. METHOD: Wnt5a expression was investigated in a large cohort of
      epithelial ovarian cancer patient samples using immunohistochemistry and
      correlated with clinicopathological variables. Wnt5a function was investigated in
      vitro in ovarian cell lines. RESULTS: Wnt5a expression was found to be
      upregulated in all major subtypes (serous, endometrioid, clear cell and mucinous)
      of epithelial ovarian cancer compared to borderline tumours and benign controls.
      Treatment of ovarian surface epithelial cells with recombinant Wnt5a decreased
      cell adhesion and was associated with increased epithelial to mesenchymal
      transition (EMT). In addition, downstream targets of beta-catenin dependent Wnt
      signalling were inhibited, and beta-catenin independent targets increased
      following Wnt5a upregulation. Knockdown of Wnt5a in ovarian cancer cells was
      associated with a mesenchymal to epithelial transition (MET), but had no
      significant effect on cell migration or proliferation. CONCLUSION: This study
      adds to the increasing evidence that Wnt signalling may play an important role in
      ovarian cancer development. Utilising an unparalleled large cohort of 623
      patients, Wnt5a protein expression was shown to be significantly higher in
      ovarian cancer patients when compared to benign and borderline ovarian tumours
      and healthy control patients. In addition, we have utilised in vitro models to
      show for the first time in ovarian cancer that Wnt5a driven non-canonical
      pathways can alter epithelial to mesenchymal transition (EMT).

PMID- 24924123
TI  - A nationwide study of serous "borderline" ovarian tumors in Denmark 1978-2002:
      centralized pathology review and overall survival compared with the general
      population.
AB  - OBJECTIVE: To describe the study population and estimate overall survival of
      women with a serous "borderline" ovarian tumor (SBT) in Denmark over 25 years
      relative to the general population. METHODS: The Danish Pathology Data Bank and
      the Danish Cancer Registry were used to identify 1487 women diagnosed with SBTs
      from 1978 to 2002. The histologic slides were collected from Danish pathology
      departments and reviewed by expert pathologists and classified as SBT/atypical
      proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma
      (LGSC). Associated implants were classified as noninvasive or invasive. Medical
      records were collected from hospital departments and reviewed. Data were analyzed
      using Kaplan-Meier and relative survival was estimated with follow-up through
      September 2, 2013. RESULTS: A cohort of 1042 women with a confirmed SBT diagnosis
      was identified. Women with stage I had an overall survival similar to the overall
      survival expected from the general population (p=0.3), whereas women with
      advanced stage disease had a poorer one (p<0.0001). This was evident both in
      women with noninvasive (p<0.0001) and invasive implants (p<0.0001). Only among
      women with advanced stage, overall survival of women with SBT/APST (p<0.0001) and
      noninvasive LGSC (p<0.0001) was poorer than expected from the general population.
      CONCLUSIONS: To date this is the largest nationwide cohort of SBTs where all
      tumors have been verified by expert pathologists. Only in women with advanced
      stage SBT, overall survival is poorer than in the general population which
      applies both to women with noninvasive and invasive implants as well as to women
      with SBT/APST and noninvasive LGSC.

PMID- 24924124
TI  - Soluble epoxide hydrolase inhibition is antinociceptive in a mouse model of
      diabetic neuropathy.
AB  - Neuropathic pain is currently an insufficiently treated clinical condition. There
      remains a critical need for efficacious therapies without severe side effects to
      treat the uniquely persistent and tonic pain of neuropathy. Inhibitors of the
      soluble epoxide hydrolase (sEH) enzyme that stabilize endogenous epoxy fatty
      acids have demonstrated antihyperalgesia in clinical chronic inflammatory pain
      and modeled neuropathic pain. Recently, the conditioned place preference assay
      has been used to evaluate the tonic nature of neuropathy in several animal
      models. The current experiments use the conditioned place preference assay
      alongside withdrawal thresholds to investigate the antihyperalgesic efficacy of
      sEH inhibitors in a murine model of diabetic neuropathy. Here, the sEH inhibitor
      trans-4-[4-(3-trifluoromethoxyphenyl-1-ureido)-cyclohexyloxy]-benzoic acid (t
      TUCB) at 10 mg/kg induced a robust place preference in diabetic neuropathic mice
      representative of pain relief. Importantly, this effect was absent both in
      control mice and in sEH-knockout mice at the same dose, indicating that t-TUCB is
      not positively reinforcing or rewarding. When compared to gabapentin, t-TUCB
      elicited a similar degree of withdrawal threshold improvement without the same
      degree of spontaneous locomotion decline in neuropathic mice. Overall, these
      experiments show that inhibiting the sEH enzyme attenuates chronic pain and
      offers an alternative to current side-effect-limited therapies to meet this
      clinical need. PERSPECTIVE: These experiments demonstrate antihyperalgesia in a
      murine chronic pain model mediated by inhibiting the sEH enzyme. The results of
      this study indicate that inhibiting the sEH is a promising alternative for
      blocking chronic pain.

PMID- 24924125
TI  - Methods to measure cytoplasmic and mitochondrial Ca(2+) concentration using
      Ca(2+)-sensitive dyes.
AB  - Ca(2+) is a ubiquitous second messenger that is involved in regulation of various
      signaling pathways. Cytoplasmic Ca(2+) is maintained at low concentrations (~100
      nM) by many active mechanisms. Increases in intracellular Ca(2+) concentration
      ([Ca(2+)]i) indeed can initiate multiple signaling pathways, depending both on
      their pattern and subcellular localization. In T cells, the stimulation of T-cell
      receptor leads to an increase in [Ca(2+)]i upon the opening of Ca(2+) release
      activated calcium (CRAC) channels. T cells can actually sustain high [Ca(2+)]i
      for several hours, resulting in the activation of transcriptional programs
      orchestrated by members of the nuclear factor of activated T-cell (NFAT) protein
      family. Here, we describe an imaging method widely employed to measure
      cytoplasmic [Ca(2+)] in naive and effector T cells based on the ratiometric dye
      Fura-2. Furthermore, we discuss a pharmacological method relying on an inhibitor
      of CRAC channels, 2-aminoethyldiphenyl borate, to validate the role of CRAC
      channels in cytoplasmic Ca(2+) elevation. Finally, we describe an approach to
      measure mitochondrial [Ca(2+)] based on another fluorescent dye, Rhod-2. With
      appropriate variations, our methodological approach can be employed to assess the
      effect and regulation of cytosolic and mitochondrial Ca(2+) waves in multiple
      experimental settings, including cultured cancer cells.

PMID- 24924126
TI  - Methods to measure intracellular Ca(2+) fluxes with organelle-targeted aequorin
      based probes.
AB  - The photoprotein aequorin generates blue light upon binding of Ca(2+) ions.
      Together with its very low Ca(2+)-buffering capacity and the possibility to add
      specific targeting sequences, this property has rendered aequorin particularly
      suitable to monitor Ca(2+) concentrations in specific subcellular compartments.
      Recently, a new generation of genetically encoded Ca(2+) probes has been
      developed by fusing Ca(2+)-responsive elements with the green fluorescent protein
      (GFP). Aequorin has also been employed to this aim, resulting in an aequorin-GFP
      chimera with the Ca(2+) sensitivity of aequorin and the fluorescent properties of
      GFP. This setup has actually solved the major limitation of aequorin, for
      example, its poor ability to emit light, which rendered it inappropriate for the
      monitoring of Ca(2+) waves at the single-cell level by imaging. In spite of the
      numerous genetically encoded Ca(2+) indicators that are currently available,
      aequorin-based probes remain the method of election when an accurate
      quantification of Ca(2+) levels is required. Here, we describe currently
      available aequorin variants and their use for monitoring Ca(2+) waves in specific
      subcellular compartments. Among various applications, this method is relevant for
      the study of the alterations of Ca(2+) homeostasis that accompany oncogenesis,
      tumor progression, and response to therapy. 

PMID- 24924127
TI  - Measuring baseline Ca(2+) levels in subcellular compartments using genetically
      engineered fluorescent indicators.
AB  - Intracellular Ca(2+) signaling is involved in a series of physiological and
      pathological processes. In particular, an intimate crosstalk between bioenergetic
      metabolism and Ca(2+) homeostasis has been shown to determine cell fate in
      resting conditions as well as in response to stress. The endoplasmic reticulum
      and mitochondria represent key hubs of cellular metabolism and Ca(2+) signaling.
      However, it has been challenging to specifically detect highly localized Ca(2+)
      fluxes such as those bridging these two organelles. To circumvent this issue,
      various recombinant Ca(2+) indicators that can be targeted to specific
      subcellular compartments have been developed over the past two decades. While the
      use of these probes for measuring agonist-induced Ca(2+) signals in various
      organelles has been extensively described, the assessment of basal Ca(2+)
      concentrations within specific organelles is often disregarded, in spite of the
      fact that this parameter is vital for several metabolic functions, including the
      enzymatic activity of mitochondrial dehydrogenases of the Krebs cycle and protein
      folding in the endoplasmic reticulum. Here, we provide an overview on genetically
      engineered, organelle-targeted fluorescent Ca(2+) probes and outline their
      evolution. Moreover, we describe recently developed protocols to quantify
      baseline Ca(2+) concentrations in specific subcellular compartments. Among
      several applications, this method is suitable for assessing how changes in basal
      Ca(2+) levels affect the metabolic profile of cancer cells. 

PMID- 24924128
TI  - Autophagy and autophagic flux in tumor cells.
AB  - Macroautophagy (hereafter referred to as autophagy), a central mechanism
      mediating the lysosomal degradation of cytoplasmic components, can be stimulated
      by a wide panel of adverse stimuli, including a panoply of anticancer agents. The
      central autophagic organelle is the autophagosome, a double membrane-bound
      vacuole that sequesters the cytoplasmic material destined to disposal. The
      ultimate destiny of the autophagosome is to fuse with a lysosome, resulting in
      the degradation of the autophagic cargo. In this setting, it is important to
      discriminate whether a particular stimulus actually promotes autophagy or it
      simply blocks the fusion of autophagosomes with lysosomes. To this aim, the
      methods that assess autophagy should assess not only the number of autophagosomes
      but also the so-called autophagic flux, that is, the clearance of the autophagy
      cargo from the lysosomal compartment. Here, we present a compendium of methods to
      assess the autophagic flux in cultured malignant cells. This approach should
      allow for the study of the intimate link between autophagy and oncometabolism in
      several experimental paradigms. 

PMID- 24924129
TI  - Methods to assess autophagy in situ--transmission electron microscopy versus
      immunohistochemistry.
AB  - Autophagy is a well-conserved lysosomal degradation pathway that plays a major
      role in both oncogenesis and tumor progression. Transmission electron microscopy
      (TEM) as well as immunohistochemistry are indispensable tools for the evaluation
      of autophagy in situ. Here, we describe an optimized protocol for the study of
      autophagic vacuoles by TEM and elaborate on the immunohistochemical detection of
      microtubule-associated protein 1 light chain (MAP1LC3, best known as LC3), which
      is currently considered as one of the most reliable markers of the autophagic
      process. The advantages, potential pitfalls, and limitations of these methods, as
      well as their value in the field of autophagy and oncometabolism research are
      discussed. Overall, we recommend a combined use of different techniques including
      TEM, immunohistochemistry, and molecular approaches (such as immunoblotting) for
      the unambiguous detection of autophagy in malignant as well as in normal tissues.

PMID- 24924130
TI  - Methods to measure the enzymatic activity of PI3Ks.
AB  - Phosphoinositide-3-kinase (PI3K) signaling has been implicated in a panoply of
      cellular responses including survival, proliferation, protein synthesis,
      migration, and vesicular trafficking. In addition, alterations in the enzymatic
      activity of PI3Ks have been involved in the pathogenesis of multiple diseases,
      ranging from cancer to chronic inflammation. The emerging interest in PI3K as a
      pharmacological target has prompted the development of several molecules with
      inhibitory activity. In this context, the quantification of the second messenger
      generated by PI3Ks, phosphoinositide-3-phosphate, offers an opportunity to
      directly test variations in the lipid kinase activity of PI3K in physiological as
      well as pathological conditions. Here, we will describe common methods to measure
      the lipid kinase activity of PI3K in vitro and new techniques to follow the
      production of phosphoinositide-3-phosphate in vivo. These methods are relevant to
      study the alterations of the PI3K systems at the interface between signaling and
      oncometabolism. 

PMID- 24924131
TI  - Luciferase-based reporter to monitor the transcriptional activity of the SIRT3
      promoter.
AB  - Sirtuin 3 (SIRT3) is a major regulator of oncometabolism. Indeed, the activity of
      SIRT3 significantly affects the response to oxidative stress, glycolytic
      proficiency, and tumorigenic potential of malignant cells. Thus, a system to
      accurately measure the transcriptional activity of the SIRT3 promoter could
      facilitate the identification of novel antineoplastic agents or have diagnostic
      applications. Here, we describe all the steps involved in the development of a
      luciferase-based reporter system to measure the activation of the human SIRT3
      promoter, encompassing the design of appropriate primers, the cloning of the
      promoter fragment, and its site-directed mutagenesis. We validated this system in
      human embryonic kidney 293T cells, taking advantage of the renowned ability of
      the transcription factor estrogen-related receptor alpha to transactivate SIRT3.
      Moreover, here we demonstrate that SIRT3 expression is responsive to rapamycin, a
      small inhibitor of mammalian target of rapamycin that has been extensively
      employed as a caloric restriction mimetic. Finally, we provide an overview of the
      complementary molecular biology techniques that might be employed to further
      verify the reliability of this system. 

PMID- 24924132
TI  - Metabolomic profiling of cultured cancer cells.
AB  - Quantitative proteomics approaches have been developed-and now begin to be
      implemented on a high-throughput basis-to fill-in the large gap between the
      genomic/transcriptomic setup of (cancer) cells and their phenotypic/behavioral
      traits, reflecting a significant degree of posttranscriptional regulation in gene
      expression as well as a robust posttranslational regulation of protein function.
      However, proteomic profiling assays not only fail to detect labile
      posttranslational modifications as well as unstable protein-to-protein
      interactions but also are intrinsically incapable of assessing the enzymatic
      activity, as opposed to the mere abundance, of a given protein. Thus, determining
      the abundance of theoretically all the metabolites contained in a
      cell/tissue/organ/organism may significantly improve the informational value of
      proteomic approaches. Several techniques have been developed to this aim,
      including high-performance liquid chromatography (HPLC) coupled to quadrupole
      time-of-flight (Q-TOF) high-resolution mass spectrometry (HRMS). This approach is
      particularly advantageous for metabolomic profiling as it offers elevated
      accuracy and improved sensitivity. Here, we describe a simple procedure to
      determine the complete complement of intracellular metabolites in cultured
      malignant cells by HPLC coupled to Q-TOF HRMS. According to this method, (1)
      cells are collected and processed to minimize contaminations as well as
      fluctuations in their metabolic profile; (2) samples are separated by HPLC and
      analyzed on a Q-TOF spectrometer; and (3) data are extracted, normalized, and
      deconvoluted according to refined mathematical methods. This protocol constitutes
      a simple approach to determine the intracellular metabolomic profile of cultured
      cancer cells. With minimal variations (mostly related to sample collection and
      processing), this method is expected to provide reliable metabolomic data on a
      variety of cellular samples. 

PMID- 24924133
TI  - Pulsed stable isotope-resolved metabolomic studies of cancer cells.
AB  - Metabolic reprogramming is a key step in oncogenic transformation, and it
      involves alterations in both bioenergetic and anabolic metabolism. Sustained by
      these metabolic alterations, malignant cells acquire the ability to re-enter the
      cell cycle and proliferate. The so-called central carbon metabolism (CCM) is the
      ultimate source for energy and building blocks enabling cellular growth and
      proliferation. The time-resolved monitoring of the conversion of stable isotope
      labeled metabolites provides profound insights into the metabolic dynamics of
      malignant cells and enables the tracking of individual carbon routes within the
      CCM. Specifically, the analysis of isotope incorporation rates within short time
      frames by means of pulsed stable isotope-resolved metabolomics (pSIRM) can be
      used to determine the dynamics of glycolysis and glutaminolysis-two metabolic
      circuitries that are often deregulated in malignant cells. Here, we detail a
      pSIRM-based method that can be applied to the study of metabolic alteration in
      cultured cancer cells. 

PMID- 24924134
TI  - Single-cell imaging for the study of oncometabolism.
AB  - Metabolic profiling is commonly employed to investigate the global metabolic
      alterations of malignant cells or tissues. In the latter setting, neoplastic
      lesions are separated from adjacent, healthy tissues and their metabolites are
      quantified upon a chromatographic run coupled to mass spectrometry. Changes in
      the abundance of specific metabolites are then mapped on metabolic networks and
      the underlying metabolic circuitries are investigated as potential targets for
      the development of novel anticancer drugs. This approach, however, does not take
      into account the intrinsic heterogeneity of neoplastic lesions, which contain a
      large amount of non-transformed cells. To circumvent this issue, techniques have
      been developed that allow for the imaging of metabolites at the single-cell
      level. Here, we summarize established protocols that are suitable for imaging
      metabolites in animal cells (be them malignant or not) as well as in plant and
      prokaryotic cells. These methods are relevant for the study of the metabolic
      alterations that accompany oncogenesis and tumor progression. 

PMID- 24924135
TI  - Study of cellular oncometabolism via multidimensional protein identification
      technology.
AB  - Cellular proteomics is becoming a widespread clinical application, matching the
      definition of bench-to-bedside translation. Among various fields of
      investigation, this approach can be applied to the study of the metabolic
      alterations that accompany oncogenesis and tumor progression, which are globally
      referred to as oncometabolism. Here, we describe a multidimensional protein
      identification technology (MuDPIT)-based strategy that can be employed to study
      the cellular proteome of malignant cells and tissues. This method has previously
      been shown to be compatible with the reproducible, in-depth analysis of up to a
      thousand proteins in clinical samples. The possibility to employ this technique
      to study clinical specimens demonstrates its robustness. MuDPIT is advantageous
      as compared to other approaches because it is direct, highly sensitive, and
      reproducible, it provides high resolution with ultra-high mass accuracy, it
      allows for relative quantifications, and it is compatible with multiplexing (thus
      limiting costs).This method enables the direct assessment of the proteomic
      profile of neoplastic cells and tissues and could be employed in the near future
      as a high-throughput, rapid, quantitative, and cost-effective screening platform
      for clinical samples. 

PMID- 24924136
TI  - In vivo quantitative proteomics for the study of oncometabolism.
AB  - The active reprograming of cellular metabolism is a primary driver of oncogenesis
      and a hallmark of established neoplastic lesions. Much of this reprogramming
      depends on the expression levels and posttranslational modifications (PTMs) of
      metabolic enzymes. Stable isotope labeling of amino acids in culture (SILAC) is
      an amino acid-based labeling technique that can be used both in vitro and in vivo
      to comparatively assess the levels and PTMs of proteins. To this aim, SILAC
      labeled cell lysates can be spiked into each sample as a standard, followed by
      the analysis of specimens by mass spectrometry (MS). Combined with appropriate
      protocols for the lysis and preparation of samples for MS, this technique allows
      for the accurate and in-depth quantification of the proteome of a wide variety of
      cell and tissue samples. In particular, SILAC can be employed to infer the
      metabolic state of neoplastic lesions and obtain a profound understanding of the
      proteomic alterations that accompany oncogenesis and tumor progression. Here, we
      describe a proteomic approach based on SILAC, high-resolution chromatography and
      high-accuracy MS for comparing levels and phosphorylation status of proteins
      between the samples of interest. This method can be applied not only to the
      proteomic study of oncometabolism in murine tissues, but also to the study of
      cellular samples and human specimens. 

PMID- 24924138
TI  - Metabolomic profiling of tumor-bearing mice.
AB  - Metabolomics is one of the newcomers among the "omics" techniques, perhaps also
      constituting the most relevant for the study of pathophysiological conditions.
      Metabolomics may indeed yield not only disease-specific biomarkers but also
      profound insights into the etiology and progression of a variety of human
      disorders. Various metabolomic approaches are currently available to study
      oncogenesis and tumor progression in vivo, in murine tumor models. Many of these
      models rely on the xenograft of human cancer cells into immunocompromised mice.
      Understanding how the metabolism of these cells evolves in vivo is critical to
      evaluate the actual pertinence of xenograft models to human pathology. Here, we
      discuss various tumor xenograft models and methods for their metabolomic
      profiling to provide a short guide to investigators interested in this field of
      research. 

PMID- 24924137
TI  - Metabolomic profiling of neoplastic lesions in mice.
AB  - Most cancers develop upon the accumulation of genetic alterations that provoke
      and sustain the transformed phenotype. Several metabolomic approaches now allow
      for the global assessment of intermediate metabolites, generating profound
      insights into the metabolic rewiring associated with malignant transformation.
      The metabolomic profiling of neoplastic lesions growing in mice, irrespective of
      their origin, can provide invaluable information on the mechanisms underlying
      oncogenesis, tumor progression, and response to therapy. Moreover, the
      metabolomic profiling of tumors growing in mice may result in the identification
      of novel diagnostic or prognostic biomarkers, which is of great clinical
      significance. Several methods can be applied to the metabolomic profiling of
      neoplastic lesions in mice, including mass spectrometry-based techniques (e.g.,
      gas chromatography-, capillary electrophoresis-, or liquid chromatography-coupled
      mass spectrometry) as well as nuclear magnetic resonance. Here, we compare and
      discuss the advantages and disadvantages of all these techniques to provide a
      concise and reliable guide for readers interested in this active area of
      investigation. 

PMID- 24924139
TI  - Metabolomic studies of patient material by high-resolution magic angle spinning
      nuclear magnetic resonance spectroscopy.
AB  - Magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy offers a
      convenient means for the rapid determination of metabolic profiles from intact
      malignant tissues with high resolution. The implementation of MAS-NMR
      spectroscopy requires minimal sample processing, hence being compatible with
      complementary histological or biochemical analyses. The metabolites routinely
      detected in (1)H MAS-NMR spectra can simultaneously inform on many of the
      metabolic alterations that characterize malignant cells, including altered
      choline metabolism and the so-called Warburg effect. Clinical MAS-NMR profiles
      have been attributed with diagnostic or prognostic value, correlating to disease
      subtype, tumor stage/grade, response to chemotherapy, and patient survival.
      Herein, the scientific rationale behind MAS-NMR and its utility for translational
      cancer research and patient stratification is summarized. Moreover, a basic
      protocol for the analysis of tumor samples by MAS-NMR spectroscopy is detailed. 

PMID- 24924140
TI  - Analysis of metabolomic profiling data acquired on GC-MS.
AB  - Gas chromatography-mass spectrometry (GC-MS) is one of the three most popular
      analytical platforms for metabolomics and is largely employed for the study of
      oncometabolism. Large volumes of data are usually generated in a GC-MS
      experiment, and many analytical steps are required to extract biologically
      relevant information from GC-MS data. These steps include (1) spectrum
      deconvolution, to convert raw data into a peak list; (2) metabolite
      identification, to recognize metabolites associated to chromatographic peaks; (3)
      quantification, to compare the abundance of a specific metabolite in different
      samples; (4) association network analysis, to reveal correlations among the
      changes in the abundance of multiple metabolites; and (5) pathway analysis, to
      understand the biochemical interrelationship between several metabolites that
      vary in a coordinated or differential manner. Here, we describe in detail the
      analytical steps that are necessary to interpret a GC-MS dataset. 

PMID- 24924141
TI  - Preface: oncometabolism: a new field of research with profound therapeutic
      implications.

PMID- 24924142
TI  - Photoperiodic effects on diapause-associated gene expression trajectories in
      European Leptinotarsa decemlineata populations.
AB  - Behavioural and physiological changes during diapause, an important strategy of
      insects for surviving harsh seasonal conditions, have been intensively studied.
      The genetic and molecular mechanisms underpinning diapause development are less
      well known. We took a candidate gene approach to study prediapause gene
      expression patterns in the Colorado potato beetle (Leptinotarsa decemlineata), an
      invasive insect that has rapidly spread northwards to high seasonality
      environments. Newly eclosed beetles originating from southern (Italy) and
      northern (Russia) Europe were reared under short- [12 h light (L):12 h dark (D)]
      and long-day (18L:6D) photoperiods for 10 days. This time period includes the
      sensitive period for the photoperiodic induction and initiation of diapause. Gene
      expression trajectories of 12 diapause-related genes (regulatory, metabolic and
      stress-resistance) were analysed from 0-, 5- and 10-day-old beetles. Gene
      expression differences increased with age, deviating significantly between
      populations and photoperiods in 10-day-old beetles. The gene expression profiles,
      particularly those related to energy metabolism and stress-resistance, indicate
      that beetles originating from Russia also prepare for diapause under the long-day
      photoperiod and show qualitative differences in the diapausing phenotype. Our
      study shows that population-dependent differences seen in behavioural and
      physiological traits connected with diapause in L. decemlineata are also evident
      in the expression trajectories of diapause-related genes.

PMID- 24924143
TI  - A kinase-phosphatase signaling module with BSK8 and BSL2 involved in regulation
      of sucrose-phosphate synthase.
AB  - External supply of sucrose to carbon-starved Arabidopsis seedlings induced
      changes in phosphorylation of Brassinosteroid Signaling Kinase 8 (BSK8) at two
      different sites. Serine S(20) lies within a phosphorylation hotspot at the N
      terminal region of the protein, while S(213) is located within the kinase domain
      of BSK8. Upon sucrose supply phosphorylation of BSK8(S20) and BSK8(S213) showed
      opposite behavior with increasing phosphorylation of S(213) and decreased
      phosphorylation of S(20) at 5 min after sucrose supply. Here we aim to
      systematically analyze the effects of BSK8 mutations on downstream cellular
      regulatory events and characterize molecular functions of BSK8 and its
      phosphorylation. Comparative phosphoproteomic profiling of a bsk8 knockout mutant
      and wild type revealed potential targets in sucrose metabolism. Activity of
      sucrose-phosphate synthase (SPS) was decreased by phosphorylation at S(152), and
      SPS phosphorylation inversely correlated with sucrose-induced BSK8 activity.
      Furthermore, BSK8 was found to interact with BSL2, a Kelch-type phosphatase. On
      the basis of a combination of kinase activity measurements, SPS activity assays,
      and phosphorylation site mutations in BSK8 at S(20) and S(213), we conclude that
      regulation of SPS by BSK8 occurs through activation of a phosphatase that in turn
      may dephosphorylate SPS and thus activates the enzyme. 

PMID- 24924144
TI  - Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like
      lectins.
AB  - Sialic acid binding immunoglobulin-like lectins (Siglecs) are cell surface
      receptors of microglia and oligodendrocytes that recognize the sialic acid cap of
      healthy neurons and neighboring glial cells. Upon ligand binding, Siglecs
      typically signal through an immunoreceptor tyrosine-based inhibition motif (ITIM)
      to keep the cell in a homeostatic status and support healthy neighboring cells.
      Siglecs can be divided into two groups; the first, being conserved among
      different species. The conserved Siglec-4/myelin-associated glycoprotein is
      expressed on oligodendrocytes and Schwann cells. Siglec-4 protects neurons from
      acute toxicity via interaction with sialic acids bound to neuronal gangliosides.
      The second group of Siglecs, named CD33-related Siglecs, is almost exclusively
      expressed on immune cells and is highly variable among different species.
      Microglial expression of Siglec-11 is human lineage-specific and prevents
      neurotoxicity via interaction with alpha2.8-linked sialic acid oligomers exposed
      on the neuronal glycocalyx. Microglial Siglec-E is a mouse CD33-related Siglec
      member that prevents microglial phagocytosis and the associated oxidative burst.
      Mouse Siglec-E of microglia binds to alpha2.8- and alpha2.3-linked sialic acid
      residues of the healthy glycocalyx of neuronal and glial cells. Recently,
      polymorphisms of the human Siglec-3/CD33 were linked to late onset Alzheimer's
      disease by genome-wide association studies. Human Siglec-3 is expressed on
      microglia and produces inhibitory signaling that decreases uptake of particular
      molecules such as amyloid-beta aggregates. Thus, glial ITIM-signaling Siglecs
      recognize the intact glycocalyx of neurons and are involved in the modulation of
      neuron-glia interaction in healthy and diseased brain. 

PMID- 24924145
TI  - Iron deficiency status irrespective of anemia: a predictor of unfavorable outcome
      in chronic heart failure patients.
AB  - OBJECTIVE: To assess the prognostic significance of iron deficiency (ID) in a
      chronic heart failure (CHF) outpatient population. METHODS AND RESULTS: We
      prospectively evaluated 127 patients with stable CHF and left ventricular
      ejection fraction <=45%. Clinical and analytical data as well as information
      regarding the occurrence of the composite endpoint of overall mortality and
      nonfatal cardiovascular events were assessed. Among the 127 patients enrolled
      [81% men, median age: 62 years (25th-75th percentile: 53-68)], 46 (36%) patients
      had ID. Women, patients with higher plasma brain natriuretic peptide levels (>400
      pg/ml) and with right ventricular systolic dysfunction presented ID more
      frequently (p < 0.05 for all). At 225 +/- 139 days of follow-up, the composite
      endpoint occurred in 15 (12%) patients. It was more frequent in ID (24 vs. 5%, p
      = 0.001) and anemic patients (25 vs. 8%, p = 0.014). In a Cox regression
      analysis, ID was associated with a higher likelihood of composite endpoint
      occurrence (HR 5.00, 95% CI 1.59-15.78, p = 0.006). In a multivariable analysis
      adjusted for clinical variables, including the presence of anemia, ID remained a
      significant predictor of the composite endpoint (HR 5.38, 95% CI 1.54-18.87, p =
      0.009). CONCLUSION: In a CHF outpatient population, ID carried a higher risk of
      unfavorable outcome, irrespectively of the presence of anemia.

PMID- 24924147
TI  - Peroxidasins: novel players in tissue genesis.
AB  - Stabilization of extracellular matrix by protein crosslinking is a universal and
      essential process in multicellular organisms. Recent findings revealed that
      peroxidasin, a unique heme-peroxidase, produces hypohalides to support matrix
      synthesis. Unexpectedly, the highly reactive and potentially damaging hypohalides
      mediate the formation of sulfilimine bonds between adjacent collagen IV
      protomers. This crosslink is a fundamental feature of basal membranes, defining
      peroxidasin-dependent oxidant generation and sulfilimine crosslink formation as
      an elemental mechanism of tissue biogenesis. 

PMID- 24924148
TI  - Reduced recognition memory is correlated with decrease in DNA methyltransferase1
      and increase in histone deacetylase2 protein expression in old male mice.
AB  - Chromatin modifying enzymes DNA methyltransferases (DNMTs), histone deacetylase
      (HDAC) 2 and CREB binding protein (CBP) play a crucial role in memory,
      particularly during consolidation process which declines with advancing age.
      However, the expression of these enzymes and their effect on memory consolidation
      during aging are not clearly understood. In the present study, novel object
      recognition test was used to assess the memory consolidation followed by
      expression analysis of DNMTs, HDAC2 and CBP in the cerebral cortex and
      hippocampus of young, adult and old male mice. Object recognition memory was
      reduced in old as compared to young and adult. DNMT1 protein expression was high
      in the cerebral cortex and hippocampus of young male mice, but declined gradually
      with age. On the other hand, HDAC2 mRNA and protein expression increased in the
      hippocampus of old male mice as compared to young and adult. Alteration in the
      expression of these enzymes is correlated with reduced recognition memory in old.

PMID- 24924149
TI  - Low levels of 1,5-anhydro-D-glucitol are associated with vascular endothelial
      dysfunction in type 2 diabetes.
AB  - BACKGROUND: Vascular endothelial dysfunction is involved in macrovascular disease
      progression in type 2 diabetes mellitus (T2DM). We reported previously that blood
      glucose fluctuations, as evaluated by continuous glucose monitoring (CGM),
      correlate with vascular endothelial function, serving as a marker of vascular
      endothelial function. However, the use of CGM is limited, suggesting the need for
      another marker of vascular endothelial function. Here, we investigated the
      relationship between vascular endothelial dysfunction and blood levels of 1,5
      anhydro-D-glucitol (1,5-AG), a marker of both postprandial hyperglycemia and
      fluctuations in blood glucose. METHODS: In 32 inpatients with T2DM and HbA1c less
      than 8.0%, the reactive hyperemia index (RHI), an index of vascular endothelial
      function, was determined by peripheral arterial tonometry. The relationships
      between RHI and 1,5-AG, blood glucose, lipid metabolism markers, and blood
      pressure, were examined. RESULTS: There was a strong correlation between 1,5-AG
      and natural logarithmic-scaled RHI (L_RHI) (r = 0.55; P = 0.001). However, there
      was no correlation between L_RHI and HbA1c, fasting blood glucose, IRI, LDL-C,
      HDL-C, TG, systolic blood pressure, or diastolic blood pressure. Multivariate
      analysis identified blood 1,5-AG levels to be the only significant and
      independent determinant of L_RHI. CONCLUSIONS: In T2DM with HbA1c <8.0%, low 1,5
      AG levels were associated with vascular endothelial dysfunction, suggesting it is
      a potentially useful marker for vascular endothelial dysfunction. TRIAL
      REGISTRATION: UMIN000015317.

PMID- 24924150
TI  - A mean field model for competition: from neutral ecology to the Red Queen.
AB  - Individual species are distributed inhomogeneously over space and time, yet,
      within large communities of species, aggregated patterns of biodiversity seem to
      display nearly universal behaviour. Neutral models assume that an individual's
      demographic prospects are independent of its species identity. They have
      successfully predicted certain static, time-independent patterns. But they have
      generally failed to predict temporal patterns, such as species ages or population
      dynamics. We construct a new, multispecies framework incorporating competitive
      differences between species, and assess the impact of this competition on static
      and dynamic patterns of biodiversity. We solve this model exactly for the special
      case of a Red Queen hypothesis, where fitter species are continually arising. The
      model predicts more realistic species ages than neutral models, without greatly
      changing predictions for static species abundance distributions. Our modelling
      approach may allow users to incorporate a broad range of ecological mechanisms. 

PMID- 24924151
TI  - Sequencing and characterization of the transcriptome of half-smooth tongue sole
      (Cynoglossus semilaevis).
AB  - BACKGROUND: Half-smooth tongue sole (Cynoglossus semilaevis) is a valuable fish
      for aquaculture in China. This fish exhibits sexual dimorphism, particularly
      different growth rates and body sizes between two genders. Thus, C. semilaevis is
      a good model that can be used to investigate mechanisms responsible for such
      dimorphism, this model can also be utilized to answer fundamental questions in
      evolution and applied fields of aquaculture. Hence, advances in second-generation
      sequencing technology, such as 454 pyrosequencing, could provide a robust tool to
      study the genome characteristics of non-model species. RESULTS: In this study, C.
      semilaevis was subjected to de novo transcriptome sequencing and
      characterization. A total of 749,954 reads were generated using a single 454
      sequencing run in a full PicoTiter plate. These reads were then assembled into
      62,632 contigs with a 10-fold average sequencing coverage. A total of 26,589
      sequences were successfully annotated based on sequence similarities; among these
      sequences, 3,451 transcripts exhibited gene ontology terms and 2,362 showed
      enzyme commissions associated with 186 pathways from Kyoto Encyclopedia of Gene
      and Genomes pathways. A search of repetitive elements was performed, and 1,898
      transposable elements were identified. Approximately 7,800 simple-sequence
      repeats and 21,234 single-nucleotide polymorphisms were also detected.
      CONCLUSIONS: Our data provided an integrated and comprehensive transcriptome
      resource for C. semilaevis. These data could be used for further research in
      population genetics, gene function, and tissue-specific gene expressions.

PMID- 24924153
TI  - Ultrasonography, FNA, mutations, hormones and thyroid nodule obsession in the
      twenty-first century: a cytopathologist's plea for reason in the age of thyroid
      storm.

PMID- 24924152
TI  - Soluble CD40-ligand (sCD40L, sCD154) plays an immunosuppressive role via
      regulatory T cell expansion in HIV infection.
AB  - CD40/CD40-ligand (CD40L) signalling is a key stimulatory pathway which triggers
      the tryptophan (Trp) catabolizing enzyme IDO in dendritic cells and is
      immunosuppressive in cancer. We reported IDO-induced Trp catabolism results in a
      T helper type 17 (Th17)/regulatory T cell (Treg ) imbalance, and favours
      microbial translocation in HIV chronic infection. Here we assessed the link
      between sCD40L, Tregs and IDO activity in HIV-infected patients with different
      clinical outcomes. Plasmatic sCD40L and inflammatory cytokines were assessed in
      anti-retroviral therapy (ART)-naive, ART-successfully treated (ST), elite
      controllers (EC) and healthy subjects (HS). Plasma levels of Trp and its
      metabolite Kynurenine (Kyn) were measured by isotope dilution tandem mass
      spectrometry and sCD14 was assessed by enzyme-linked immunosorbent assay (ELISA).
      IDO-mRNA expression was quantified by reverse transcription-polymerase chain
      reaction (RT-PCR). The in-vitro functional assay of sCD40L on Treg induction and
      T cell activation were assessed on peripheral blood mononuclear cells (PBMCs)
      from HS. sCD40L levels in ART-naive subjects were significantly higher compared
      to ST and HS, whereas EC showed only a minor increase. In ART-naive alone, sCD40L
      was correlated with T cell activation, IDO-mRNA expression and CD4 T cell
      depletion but not with viral load. sCD40L was correlated positively with IDO
      enzymatic activity (Kyn/Trp ratio), Treg frequency, plasma sCD14 and inflammatory
      soluble factors in all HIV-infected patients. In-vitro functional sCD40L
      stimulation induced Treg expansion and favoured Treg differentiation by reducing
      central memory and increasing terminal effector Treg proportion. sCD40L also
      increased T cell activation measured by co-expression of CD38/human leucocyte
      antigen D-related (HLA-DR). These results indicate that elevated sCD40L induces
      immunosuppression in HIV infection by mediating IDO-induced Trp catabolism and
      Treg expansion.

PMID- 24924155
TI  - Affective motives for smoking among early stage smokers.
AB  - BACKGROUND: As most smokers initiate smoking during adolescence, assessment of
      smoking motives that underlie trajectories of dependence is critical for both
      prevention and cessation efforts. In the current study, we expected participants
      with higher nicotine dependence would smoke (a) less for positive reinforcement
      (PR) and (b) more for negative reinforcement (NR) motives. We secondarily
      assessed the relative contribution of PR to NR motives across levels of
      dependence. METHODS: Data were drawn from a study on cue-elicited craving among
      occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking
      motives were assessed in relation to 3 commonly used measures of nicotine
      dependence: (a) Fagerstrom Test for Nicotine Dependence (FTND), (b) Autonomy over
      Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS).
      RESULTS: Compared to occasional smokers, daily smokers had significantly higher
      scores on each dependence measure and endorsed more prominent NR smoking motives.
      Each measure of nicotine dependence was strongly associated with NR motives for
      smoking, although measures differed in their association with PR motives. As
      expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive
      difference score (PR - NR), such that higher dependence was associated with more
      prominent NR motives for smoking. CONCLUSIONS: Results are consistent with our
      understanding of dependence and provide further support for 3 common measures of
      nicotine dependence among early stage smokers.

PMID- 24924156
TI  - Definitions of sleeplessness in children with attention-deficit hyperactivity
      disorder (ADHD): implications for mothers' mental state, daytime sleepiness and
      sleep-related cognitions.
AB  - BACKGROUND: Sleep disturbances are common in children with attention-deficit
      hyperactivity disorder (ADHD). Sleeplessness is frequently reported although
      results are inconsistent perhaps because different definitions for it are
      applied. This study looked at maternal functioning and child objective sleep
      patterns in relation to different definitions of sleeplessness in children with
      ADHD. METHODS: The study included 45 children (aged 3-14 years) with ADHD and
      their mothers. Sleeplessness was defined according to: (i) yes/no report of
      whether mothers thought their children had a problem with sleeplessness (Maternal
      definition MD) and (ii) mothers' responses to a quantitative standardized
      questionnaire (Quantitative definition QD) designed to detect the frequency and
      duration of parent-reported problems with settling, night waking and early
      waking. Objective sleep patterns were also assessed by means of actigraphy.
      Maternal mental health, daytime sleepiness and cognitions related to child sleep
      were assessed by questionnaire. RESULTS: Both definitions appeared to tap similar
      although slightly different constructs. There were no group differences in
      objective sleep patterns. Maternal mental health was found to be significantly
      worse in the mothers who considered their child to be sleepless (MD) (P < 0.025),
      but not in those mothers whose child was found to be sleepless according to the
      standardized criteria (QD). Maternal sleepiness did not differ between groups.
      For both categories of sleepless children (MD and QD), the mothers had
      significantly more doubts about their competency as a parent (P < 0.01 and P <
      0.025, respectively) compared to mothers of children without sleeplessness.
      CONCLUSIONS: Two different maternal assessments of child sleeplessness in
      children with ADHD may assess subtly different constructs, but both may provide
      useful information about potential problems across the family.

PMID- 24924157
TI  - Stimulant use and its impact on growth in children receiving growth hormone
      therapy: an analysis of the KIGS International Growth Database.
AB  - BACKGROUND: Children receiving stimulants for attention deficit hyperactivity
      disorder (ADHD) frequently present to pediatric endocrinology clinics for
      evaluation and treatment of growth disorders. The worldwide prevalence of
      stimulant use in children with ADHD also receiving recombinant human growth
      hormone (rhGH) and the impact on response to rhGH are unknown. METHODS: Data on
      children enrolled in the KIGS(r) (Pfizer International Growth Study) registry
      were evaluated for the associated diagnosis of ADHD prior to initiation of
      Genotropin(r) rhGH. Concomitant stimulant medications and auxological information
      were captured. Response to rhGH was evaluated using established growth prediction
      models. RESULTS: The prevalence of ADHD in KIGS was 2.3% (1,748/75,251), with
      stimulants used in 1.8% (1,326/75,251). Children with idiopathic growth hormone
      deficiency (IGHD) who received stimulants grew significantly less (1.1 cm) in the
      first year of rhGH therapy than expected for rhGH-treated non-ADHD IGHD children.
      After one year of rhGH, idiopathic short stature (ISS) children with ADHD were
      significantly shorter [0.74 cm (with stimulants) and 0.69 cm (without
      stimulants)] than non-ADHD ISS children. CONCLUSIONS: We demonstrated an impaired
      response to rhGH in IGHD and ISS children with ADHD. Our findings suggest that
      the ADHD phenotype, alone or in conjunction with stimulant therapy, may impair
      the short-term growth response to rhGH.

PMID- 24924158
TI  - A Comparison of Urge Intensity and the Probability of Tic Completion During Tic
      Freely and Tic Suppression Conditions.
AB  - Tic-suppression-based treatments (TSBTs) represent a safe and effective treatment
      option for Chronic Tic Disorders (CTDs). Prior research has demonstrated that
      treatment naive youths with CTDs have the capacity to safely and effectively
      suppress tics for prolonged periods. It remains unclear how tic suppression is
      achieved. The current study principally examines how effective suppression is
      achieved and preliminary correlates of the ability to suppress tics. Twelve
      youths, ages 10 to 17 years, with moderate-to-marked CTDs participated in an
      alternating sequence of tic freely and reinforced tic suppression conditions
      during which urge intensity and tic frequency were frequently assessed.
      Probability of tics occurring was half as likely following high-intensity urges
      during tic suppression (31%) in contrast to low-intensity urges during tic freely
      conditions (60%). Age was not associated with ability to suppress. Intelligence
      indices were associated with or trended toward greater ability to suppress tics.
      Attention difficulties were not associated with ability to suppress but were
      associated with tic severity. In contrast to our "selective suppression"
      hypothesis, we found participants equally capable of suppressing their tics
      regardless of urge intensity during reinforced tic suppression. Tic suppression
      was achieved with an "across-the-board" effort to resist urges. Preliminary data
      suggest that ability to suppress may be associated with general cognitive
      variables rather than age, tic severity, urge severity, and attention. Treatment
      naive youths appear to possess a capacity for robust tic suppression. TSBTs may
      bolster these capacities and/or enable their broader implementation, resulting in
      symptom improvement. 

PMID- 24924159
TI  - Repartnering After Widowhood.
AB  - OBJECTIVES: This study estimates the sex-specific prevalence of repartnering
      after widowhood. The main objective is to examine the competing choice between
      nonmarital cohabitation and remarriage as well as repartnering differentials.
      METHODS: The study uses data from the 2007 Canadian General Social Survey and
      life table methods to illustrate gender and regional differences in the
      cumulative proportion of people aged 45 and older who repartner after widowhood.
      Proportional hazard models are used to examine how factors such as socioeconomic
      resources, region, demographic characteristics, and health associate with the
      risk of repartnering and repartnering preferences. RESULTS: Most repartnering
      after widowhood occurs within ten years of this event or not at all. Ten years
      after widowhood, about 7% of widows and 29% of widowers have formed a new union.
      For both widows and widowers, the rate of remarriage is twice as high as the rate
      of cohabitation. The exception to this is the province of Quebec, where
      cohabitation is a more prevalent choice of repartnering than remarriage. There is
      a weak association between socioeconomic resources and both the risk of
      cohabitation and remarriage. DISCUSSION: Our results confirm that constraints in
      marriage markets appear to contribute to a gender gap in the prevalence of
      repartnering after widowhood. Though the widowed prefer remarriage over
      cohabitation as a repartnering choice, there are important regional differences
      in repartnering that reflect cultural norms in the social acceptance of
      cohabitation. Socioeconomic disincentives to marriage do not appear to push the
      widowed into cohabitation.

PMID- 24924160
TI  - Depressive Mood, Anger, and Daily Cortisol of Caregivers on High- and Low-Stress
      Days.
AB  - OBJECTIVES: This study examines the association of daily cortisol with depressive
      mood and anger. METHOD: Depressive mood, anger and 2 markers of cortisol, area
      under the curve (AUC), and cortisol awakening response (CAR) were examined for
      caregivers (N = 164) of individuals with dementia (IWDs) across 8 days, some of
      which IWDs attended an adult day service (ADS) program. Caregivers were primarily
      female (86.7%) with a mean age of 61.99. First, multilevel models were run with
      CAR and AUC each as separate covariates of anger and depressive mood. A second
      set of models examined contextual factors of caregivers (i.e., care-related
      stressors and amount of ADS use) were added to the models for anger and
      depressive mood (Model 2). RESULTS: On days where caregivers had AUCs below their
      average they expressed higher anger scores. However in Model 2, anger was
      associated with more care-related stressors, but not ADS use or daily cortisol.
      Caregivers who on average had smaller CARs were more likely to be depressed. In
      Model 2, depressed mood was associated with more care-related stressors and a low
      average CAR. DISCUSSION: We found that hypocortisol patterns, reflective of
      chronic stress experienced by caregivers, are associated with negative mood.

PMID- 24924161
TI  - Does embeddedness protect? Personal network density and vulnerability to
      mistreatment among older American adults.
AB  - OBJECTIVES: This study considers the association between personal network density
      and risk of elder mistreatment among American adults. METHOD: Using egocentric
      network data from the National Social Life, Health, and Aging Project, we employ
      logistic and negative binomial regression to predict recent experience of elder
      mistreatment. We further unpack the density mistreatment association by linking
      perpetrators to the victim's network and by assessing their position within its
      structure. RESULTS: As hypothesized, older adults with dense networks had a lower
      risk of elder mistreatment. Interestingly, the perpetrators of these harmful acts
      were often found within seniors' close networks-though there was little evidence
      to suggest that perpetrators themselves were poorly embedded in the network.
      DISCUSSION: Results highlight how network-level phenomena can operate
      distinctively from dyadic mistreatment processes. Dense personal networks seem to
      provide structural protection against elder mistreatment, even as many offensive
      acts are committed by those that are close to the victim and relatively well
      embedded in their network.

PMID- 24924162
TI  - The Paget Bicentenary: An Australian perspective.
AB  - The year 2014 marks the bicentenary of the birth of Sir James Paget (1814-1899),
      the celebrated English surgeon and pathologist. Although best known for his work
      on bone and breast disease, Paget also played an important role in the
      institution of Australia's first medical school. In this article, that
      involvement and Paget's other antipodean influences are summarised. The naming of
      Paget's disease of the bone is also discussed.

PMID- 24924163
TI  - Molecular epidemiology of infant botulism in California and elsewhere, 1976-2010.
AB  - BACKGROUND: Infant botulism (IB), first identified in California in 1976, results
      from Clostridium botulinum spores that germinate, multiply, and produce botulinum
      neurotoxin (BoNT) in the immature intestine. From 1976 to 2010 we created an
      archive of 1090 BoNT-producing isolates consisting of 1012 IB patient (10
      outpatient, 985 hospitalized, 17 sudden death), 25 food, 18 dust/soils, and 35
      other strains. METHODS: The mouse neutralization assay determined isolate toxin
      type (56% BoNT/A, 32% BoNT/B). Amplified fragment-length polymorphism (AFLP)
      analysis of the isolates was combined with epidemiologic information. RESULTS:
      The AFLP dendrogram, the largest to date, contained 154 clades; 52% of isolates
      clustered in just 2 clades, 1 BoNT/A (n=418) and 1 BoNT/B (n=145). These clades
      constituted an endemic C. botulinum population that produced the entire clinical
      spectrum of IB. Isolates from the patient's home environment (dust/soil, honey)
      usually located to the same AFLP clade as the patient's isolate, thereby
      identifying the likely source of infective spores. C. botulinum A(B) strains were
      identified in California for the first time. CONCLUSIONS: Combining molecular
      methods and epidemiological data created an effective tool that yielded novel
      insights into the genetic diversity of C. botulinum and the clinical spectrum,
      occurrence, and distribution of IB in California.

PMID- 24924165
TI  - A new myeloarchitectonic map of the human neocortex based on data from the Vogt
      Vogt school.
AB  - The human cerebral cortex contains numerous myelinated fibres, the arrangement
      and density of which is by no means homogeneous throughout the cortex. Local
      differences in the spatial organization of these fibres render it possible to
      recognize areas with a different myeloarchitecture. The neuroanatomical
      subdiscipline aimed at the identification and delineation of such areas is known
      as myeloarchitectonics. During the period extending from 1910 to 1970, Oscar and
      Cecile Vogt and their numerous collaborators (The Vogt-Vogt school) published a
      large number of myeloarchitectonic studies on the cortex of the various lobes of
      the human cerebrum. Recently, one of us (Nieuwenhuys in Brain Struct Funct 218:
      303-352, 2013) extensively reviewed these studies. It was concluded that the data
      available are adequate and sufficient for the composition of a myeloarchitectonic
      map of the entire human neocortex. The present paper is devoted to the creation
      of this map. Because the data provided by the Vogt-Vogt school are derived from
      many different brains, a standard brain had to be introduced to which all data
      available could be transferred. As such, the colin27 structural scan, aligned to
      the MNI305 template was selected. The procedure employed in this transfer
      involved computer-aided transformations of the lobar maps available in the
      literature, to the corresponding regions of the standard brain, as well as local
      adjustments in the border zones of the various lobes. The resultant map includes
      180 myeloarchitectonic areas, 64 frontal, 30 parietal, 6 insular, 17 occipital
      and 63 temporal. The designation of the various areas with simple Arabic numbers,
      introduced by Oscar Vogt for the frontal and parietal cortices, has been extended
      over the entire neocortex. It may be expected that combination of the
      myeloarchitectonic data of the Vogt-Vogt school, as expressed in our map, with
      the results of the detailed cytoarchitectonic and receptor architectonic studies
      of Karl Zilles and Katrin Amunts and their numerous associates, will yield a
      comprehensive 'supermap' of the structural organization of the human neocortex.
      For the time being, i. e., as long as this 'supermap' is not yet available, our
      map may provide a tentative frame of reference for (a) the morphological
      interpretation of the results of functional neuroimaging studies; (b) the
      selection of starting points (seed voxels, regions-of-interest) in diffusion
      tractography studies and

PMID- 24924164
TI  - HIV reverse-transcriptase drug resistance mutations during early infection reveal
      greater transmission diversity than in envelope sequences.
AB  - BACKGROUND: Drug resistance mutations (DRMs) can serve as distinct,
      nonpolymorphic markers for evaluating diversity of expressed HIV-1. We screened
      for DRMs during early-acute viremia and examined the diversity in reverse
      transcriptase (RT) relative to envelope (env) in cases of transmitted drug
      resistance. METHODS: We evaluated 111 longitudinal plasma samples collected every
      2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000.
      The samples were screened with sensitive polymerase chain reaction assays for the
      commonly transmitted M41L and K70R mutations and for K65R, which was undetected
      by bulk sequencing. Mutation-positive samples were further characterized by
      clonal sequencing of RT and env V1-V3. RESULTS: Drug resistance mutations were
      detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression;
      most mutations disappeared about the time of seroconversion. Clonal sequencing
      verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R coexisted
      unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of
      1.6%-23.0%. In one seroconverter, variants with M184V and nonnucleoside RT
      inhibitor mutations were also identified at first RNA expression. Each
      seroconverter displayed a homogeneous V1-V3 env population. CONCLUSIONS: Reverse
      transcriptase DRMs demonstrate that the breadth of variants in transmission may
      be greater than what is reflected in envelope sequences.

PMID- 24924166
TI  - Historical perspective on the introduction and use of chemotherapy for the
      treatment of osteosarcoma.
AB  - Chemotherapy for treatment of osteosarcoma was demonstrated to be effective in
      eradicating primary tumor and pulmonary metastases in the mid-twentieth century.
      The first agents that held promise were doxorubicin and high-dose methotrexate
      with leucovorin (citrovorin factor) in the mid-1970s. Since then, other agents
      that can eliminate or cause regression of tumor have been discovered: cis
      diamminedichloroplatinum II (cisplatin) and the oxazaphosphorines ifosfamide and
      cyclophosphamide. Additional agents await further study to define their
      potential. The effective agents have been utilized in various combination
      regimens and have escalated the survival rate from <10 to 75 %. They have also
      enabled pulmonary metastectomy in patients with persistent and/or recurrent
      pulmonary metastases and tumor ablation and limb salvage in 80 % of newly
      diagnosed patients. Unfortunately, however, despite these impressive advances no
      change in survival expectancy of patients with osteosarcoma during the past 40
      years has occurred. There have been no new chemotherapeutic agents effective in
      addressing disease that is resistant to current agents; the few that have been
      introduced await further study to substantiate their efficacy. This also includes
      attempts at alternate administration of chemotherapy (intra-arterial and
      inhalation therapy.) In this chapter, we provide an account of the sequential
      introduction of the chemotherapeutic agents, review the results of their
      application in selected regimens, and discuss the role of neoadjuvant
      chemotherapy. 

PMID- 24924167
TI  - Wnt signaling in osteosarcoma.
AB  - Osteosarcoma (OS) is the most common primary bone malignancy diagnosed in
      children and adolescents with a high propensity for local invasion and distant
      metastasis. Despite current multidisciplinary treatments, there has not been a
      drastic change in overall prognosis within the last two decades. With current
      treatments, 60-70 % of patients with localized disease survive. Given a
      propensity of Wnt signaling to control multiple cellular processes, including
      proliferation, cell fate determination, and differentiation, it is a critical
      pathway in OS disease progression. At the same time, this pathway is extremely
      complex with vast arrays of cross-talk. Even though decades of research have
      linked the role of Wnt to tumorigenesis, there are still outstanding areas that
      remain poorly understood and even controversial. The canonical Wnt pathway
      functions to regulate the levels of the transcriptional co-activator beta
      catenin, which ultimately controls key developmental gene expressions. Given the
      central role of this mediator, inhibition of Wnt/beta-catenin signaling has been
      investigated as a potential strategy for cancer control. In OS, several secreted
      protein families modulate the Wnt/beta-catenin signaling, including secreted
      Frizzled-related proteins (sFRPs), Wnt inhibitory protein (WIF), Dickkopf
      proteins (DKK-1,2,3), sclerostin, and small molecules. This chapter focuses on
      our current understanding of Wnt/beta-catenin signaling in OS, based on recent in
      vitro and in vivo data. Wnt activates noncanonical signaling pathways as well
      that are independent of beta-catenin which will be discussed. In addition, stem
      cells and their association with Wnt/beta-catenin are important factors to
      consider. Ultimately, the multiple canonical and noncanonical Wnt/beta-catenin
      agonists and antagonists need to be further explored for potential targeted
      therapies. 

PMID- 24924168
TI  - Receptor tyrosine kinases in osteosarcoma: not just the usual suspects.
AB  - Despite aggressive surgical and chemotherapy protocols, survival rates for
      osteosarcoma patients have not improved over the last 30 years. Therefore, novel
      therapeutic agents are needed. Receptor tyrosine kinases have emerged as targets
      for the development of new cancer therapies since their activation leads to
      enhanced proliferation, survival, and metastasis. In fact, aberrant expression
      and activation of RTKs have been associated with the progression of many cancers.
      Studies from our lab using phosphoproteomic screening identified RTKs that are
      activated and thus may contribute to the signaling within metastatic human
      osteosarcoma cells. Functional genomic screening using siRNA was performed to
      distinguish which of the activated RTKs contribute to in vitro phenotypes
      associated with metastatic potential (motility, invasion, colony formation, and
      cell growth). The resulting RTK hits were then validated using independent
      validation experiments. From these results, we identified four RTKs (Axl, EphB2,
      FGFR2, and Ret) that have not been previously studied in osteosarcoma and provide
      targets for the development of novel therapeutics. 

PMID- 24924169
TI  - Understanding the role of Notch in osteosarcoma.
AB  - The Notch pathway has been described as an oncogene in osteosarcoma, but the
      myriad functions of all the members of this complex signaling pathway, both in
      malignant cells and nonmalignant components of tumors, make it more difficult to
      define Notch as simply an oncogene or a tumor suppressor. The cell-autonomous
      behaviors caused by Notch pathway manipulation may vary between cell lines but
      can include changes in proliferation, migration, invasiveness, oxidative stress
      resistance, and expression of markers associated with stemness or tumor
      initiating cells. Beyond these roles, Notch signaling also plays a vital role in
      regulating tumor angiogenesis and vasculogenesis, which are vital aspects of
      osteosarcoma growth and behavior in vivo. Further, osteosarcoma cells themselves
      express relatively low levels of Notch ligand, making it likely that nonmalignant
      cells, especially endothelial cells and pericytes, are the major source of Notch
      activation in osteosarcoma tumors in vivo and in patients. As a result, Notch
      pathway expression is not expected to be uniform across a tumor but likely to be
      highest in those areas immediately adjacent to blood vessels. Therapeutic
      targeting of the Notch pathway is likewise expected to be complicated. Most
      pharmacologic approaches thus far have focused on inhibition of gamma secretase,
      a protease of the presenilin complex. This enzyme, however, has numerous other
      target proteins that would be expected to affect osteosarcoma behavior, including
      CD44, the WNT/beta-catenin pathway, and Her-4. In addition, Notch plays a vital
      role in tissue and organ homeostasis in numerous systems, and toxicities,
      especially GI intolerance, have limited the effectiveness of gamma secretase
      inhibitors. New approaches are in development, and the downstream targets of
      Notch pathway signaling also may turn out to be good targets for therapy. In
      summary, a full understanding of the complex functions of Notch in osteosarcoma
      is only now unfolding, and this deeper knowledge will help position the field to
      better utilize novel therapies as they are developed. 

PMID- 24924170
TI  - Developmental pathways hijacked by osteosarcoma.
AB  - Cancer of any type often can be described by an arrest, alteration or disruption
      in the normal development of a tissue or organ, and understanding of the normal
      counterpart's development can aid in understanding the malignant state. This is
      certainly true for osteosarcoma and the normal developmental pathways that guide
      osteoblast development that are changed in the genesis of osteogenic sarcoma. A
      carefully regulated crescendo-decrescendo expression of RUNX2 accompanies the
      transition from mesenchymal stem cell to immature osteoblast to mature
      osteoblast. This pivotal role is controlled by several pathways, including bone
      morphogenic protein (BMP), Wnt/beta-catenin, fibroblast growth factor (FGF), and
      protein kinase C (PKC). The HIPPO pathway and its downstream target YAP help to
      regulate proliferation of immature osteoblasts and their maturation into non
      proliferating mature osteoblasts. This pathway also helps regulate expression of
      the mature osteoblast protein osteocalcin. YAP also regulates expression of MT1
      MMP, a membrane-bound matrix metalloprotease responsible for remodeling the
      extracellular matrix surrounding the osteoblasts. YAP, in turn, can be regulated
      by the ERBB family protein Her-4. Osteosarcoma may be thought of as a cell held
      at the immature osteoblast stage, retaining some of the characteristics of that
      developmental stage. Disruptions of several of these pathways have been described
      in osteosarcoma, including BMP, Wnt/b-catenin, RUNX2, HIPPO/YAP, and Her-4.
      Further, PKC can be activated by several receptor tyrosine kinases implicated in
      osteosarcoma, including the ERBB family (EGFR, Her-2 and Her-4 in osteosarcoma),
      IGF1R, FGF, and others. Understanding these functions may aid in the
      understanding the mechanisms underpinning clinical observations in osteosarcoma,
      including both the lytic and blastic phenotypes of tumors, the invasiveness of
      the disease, and the tendency for treated tumors to ossify rather than shrink.
      Through a better understanding of the relationship between normal osteoblast
      development and osteosarcoma, we may gain insights into novel therapeutic avenues
      and improved outcomes. 

PMID- 24924171
TI  - MicroRNAs in osteosarcomagenesis.
AB  - The etiology of osteosarcoma (OS) remains enigmatic. Particular clinical and
      molecular patterns, observed with high frequency in OS, suggest that it results
      from some yet-to-be-discovered central driver. How else can biology generate such
      an aggressive, metastatic, genetically and chromosomally unstable malignancy with
      virtually no apparent precursor neoplasms that are partway along a disease path
      toward OS? With this conundrum as a backdrop, the discovery of every new native
      molecule with power to impact a cell's biology is usually quickly followed by a
      search to see if this type of molecule contains the key to unlock OS biology. 

PMID- 24924172
TI  - RECQ DNA helicases and osteosarcoma.
AB  - The RECQ family of DNA helicases is a conserved group of enzymes that are
      important for maintaining genomic integrity. In humans, there are five RECQ
      helicase genes, and mutations in three of them-BLM, WRN, and RECQL4-are
      associated with the genetic disorders Bloom syndrome, Werner syndrome, and
      Rothmund-Thomson syndrome (RTS), respectively. Importantly all three diseases are
      cancer predisposition syndromes. Patients with RTS are highly and uniquely
      susceptible to developing osteosarcoma; thus, RTS provides a good model to study
      the pathogenesis of osteosarcoma. The "tumor suppressor" role of RECQL4 and the
      other RECQ helicases is an area of active investigation. This chapter reviews
      what is currently known about the cellular functions of RECQL4 and how these may
      relate to tumorigenesis, as well as ongoing efforts to understand RECQL4's
      functions in vivo using animal models. Understanding the RECQ pathways may
      provide insight into avenues for novel cancer therapies in the future. 

PMID- 24924173
TI  - Autophagy in osteosarcoma.
AB  - Osteosarcoma (OS) metastatic disease is resistant to conventional chemotherapy.
      Tumor resistance to chemotherapy has been one of the major areas of concern to
      clinicians and the topic of many laboratory investigators. Evaluation of
      mechanisms implicated in OS lung metastasis resistance to chemotherapy has been
      the focus of some of our most recent work. We have previously demonstrated the
      therapeutic efficacy of aerosol gemcitabine (GCB) in OS lung metastases. However,
      a subset of cells fails to respond to GCB treatment and persists as isolated lung
      metastases in vivo. Autophagy, a physiological mechanism that supports
      nutritional deprivation under stressful conditions, has been implicated in tumor
      resistance to chemotherapy. We demonstrated the induction of autophagy by GCB in
      LM7 metastatic human OS cells and K7M3 metastatic murine OS cells. Inhibition of
      autophagy resulted in increased sensitivity to GCB in LM7 cells. By contrast,
      inhibiting autophagy in K7M3 cells decreased GCB sensitivity. Defining the role
      autophagy plays in chemotherapy response in different tumor types has become of
      greater importance in order to identify the best suitable therapeutic approach.
      In this chapter, we summarize some of the most recent work related to autophagy
      in OS, identify some of the known mechanisms, and address the different roles
      autophagy plays in chemotherapy response. 

PMID- 24924174
TI  - HER-2 involvement in osteosarcoma.
AB  - The major goals of translational research in osteosarcoma entail the
      identification of prognostic factors and therapeutic targets. Given the relevance
      of epidermal growth factor receptor pathway to breast cancer and the finding that
      HER-2 was expressed in a proportion of osteosarcoma, it was reasonable to
      investigate this pathway further. Investigations of HER-2 in osteosarcoma have
      led to the publication of numerous conflicting reports with regard to the level
      and prognostic value of HER-2 expression, which are reviewed and discussed.
      Numerous lessons provided by this research experience are described. This pathway
      has also been explored as a therapeutic target with at least one study of
      trastuzumab for the treatment of osteosarcoma completed. Other studies utilizing
      alternative approaches to target the HER-2 receptor for the treatment of
      osteosarcoma have been considered. 

PMID- 24924175
TI  - Role of ezrin in osteosarcoma metastasis.
AB  - The cause of death for the vast majority of cancer patients is the development of
      metastases at sites distant from that of the primary tumor. For most pediatric
      sarcoma patients such as those with osteosarcoma (OS), despite successful
      management of the primary tumor through multimodality approaches, the development
      of metastases, commonly to the lungs, is the cause of death. Significant
      improvements in long-term outcome for these patients have not been seen in more
      than 30 years. Furthermore, the long-term outcome for patients who present with
      metastatic disease is grave [1-5]. New treatment options are needed.Opportunities
      to improve outcomes for patients who present with metastases and those at-risk
      for progression and metastasis require an improved understanding of cancer
      progression and metastasis. With this goal in mind we and others have identified
      ezrin as a metastasis-associated protein that associated with OS and other
      cancers. Ezrin is the prototypical ERM (Ezrin/Radixin/Moesin) protein family
      member. ERMs function as linker proteins connecting the actin cytoskeleton and
      the plasma membrane. Since our initial identification of ezrin in pediatric
      sarcoma, an increasing understanding the role of ezrin in metastasis has emerged.
      Briefly, ezrin appears to allow metastatic cells to overcome a number of stresses
      experienced during the metastatic cascade, most notably the stress experienced as
      cells interact with the microenvironment of the secondary site. Cells must
      rapidly adapt to this environment in order to survive. Evidence now suggests a
      connection between ezrin expression and a variety of mechanisms linked to this
      important cellular adaptation including the ability of metastatic cells to
      initiate the translation of new proteins and to allow the efficient generation of
      ATP through a variety of sources. This understanding of the role of ezrin in the
      biology of metastasis is now sufficient to consider ezrin as an important
      therapeutic target in osteosarcoma patients. This chapter reviews our
      understanding of ezrin and the related ERM proteins in normal tissues and
      physiology, summarizes the expression of ezrin in human cancers and associations
      with clinical parameters of disease progression, reviews reports that detail a
      biological understanding of ezrin's role in metastatic progression, and concludes
      with a rationale that may be considered to target ezrin and ezrin biology in
      osteosarcoma. 

PMID- 24924176
TI  - Participation of the Fas/FasL signaling pathway and the lung microenvironment in
      the development of osteosarcoma lung metastases.
AB  - The lungs are the most common site for the metastatic spread of osteosarcoma.
      Success in using chemotherapy to improve overall survival has reached a plateau.
      Understanding the biologic properties that permit osteosarcoma cells to grow in
      the lungs may allow the identification of novel therapeutic approaches-the goal
      being to alter the tumor cells' expression of cell surface proteins so that there
      is no longer compatibility with the metastatic niche. We have demonstrated that
      the Fas Ligand positive (FasL(+)) lung microenvironment eliminates Fas(+)
      osteosarcoma cells that metastasize to the lungs. Indeed, osteosarcoma lung
      metastases from patients are Fas(-), similar to what we found in several
      different mouse models. The Fas(+) cells are cleared from the lungs through
      apoptosis induced by the Fas signaling pathway following interaction of Fas on
      the tumor cell surface with the lung FasL. Blocking the Fas signaling pathway
      interferes with this process, allowing the Fas(+) cells to grow in the lungs. Our
      investigations show that Fas expression in osteosarcoma cells is regulated
      epigenetically by the micro-RNA miR-20a, encoded by the miR-17-92 cluster. Our
      studies support the feasibility of finding agents that can re-induce Fas
      expression as a novel therapeutic approach to treat osteosarcoma patients with
      lung metastases. We have identified two such agents, the histone deacetylase
      inhibitor entinostat and the chemotherapeutic agent gemcitabine (GCB). Aerosol
      GCB and oral entinostat induce the upregulation of Fas and the regression of
      established osteosarcoma lung metastases. Aerosol GCB was not effective in the
      FasL-deficient gld mouse confirming that the lung microenvironment was central to
      the success of this therapy. Our studies establish the critical role of the lung
      microenvironment in the metastatic process of osteosarcoma to the lungs and
      suggest an alternative focus for therapy, that is, incorporating the lung
      microenvironment as part of the treatment strategy against established
      osteosarcoma disease in the lungs. 

PMID- 24924177
TI  - Zebrafish as a model for human osteosarcoma.
AB  - For various reasons involving biological comparativeness, expansive technological
      possibilities, accelerated experimental speed, and competitive costs, zebrafish
      has become a comprehensive model for cancer research. Hence, zebrafish embryos
      and full-grown fish have been instrumental for studies of leukemia, melanoma,
      pancreatic cancer, bone tumors, and other malignancies. Although because of its
      similarities to human osteogenesis zebrafish appears to be an appealing model to
      investigate osteosarcoma, only a few osteosarcoma specific studies have been
      accomplished yet. Here, we review interesting related and unrelated reports of
      which the findings might be extrapolated to osteosarcoma. More importantly,
      rational but yet unexplored applications of zebrafish are debated to expand the
      window of opportunities for future establishment of osteosarcoma models.
      Accordingly technological advances of zebrafish based cancer research, such as
      robotic high-throughput multicolor injection systems and advanced imaging methods
      are discussed. Furthermore, various use of zebrafish embryos for screening drug
      regimens by combinations of chemotherapy, novel drug deliverers, and immune
      system modulators are suggested. Concerning the etiology, the high degree of
      genetic similarity between zebrafish and human cancers indicates that affected
      regions are evolutionarily conserved. Therefore, zebrafish as a swift model
      system that allows for the investigation of multiple candidate gene-defects is
      presented. 

PMID- 24924178
TI  - Using canine osteosarcoma as a model to assess efficacy of novel therapies: can
      old dogs teach us new tricks?
AB  - Since its domestication more than 10,000 years ago, the dog has been the animal
      that most intimately shares our work and homelife. Interestingly, the dog also
      shares many of our diseases including cancer such as osteosarcoma. Like the
      human, osteosarcoma is the most common bone malignancy of the dog and death from
      pulmonary metastasis is the most common outcome. The incidence of this
      spontaneous bone neoplasm occurs ten times more frequently that it does so in
      children with about 8,000-10,000 cases estimated to occur in dogs in the USA.
      Because there is no "standard of care" in veterinary medicine, the dog can also
      serve us by being a model for this disease in children. Although the most common
      therapy for the dog with osteosarcoma is amputation followed by chemotherapy, not
      all owners choose this route. Consequently, novel therapeutic interventions can
      be attempted in the dog with or without chemotherapy that could not be done in
      humans with osteosarcoma due to ethical concerns. This chapter will focus on the
      novel therapies in the dog that have been reported or are in veterinary clinical
      trials at the author's institution. It is hoped that collaboration between
      veterinary oncologists and pediatric oncologists will lead to the development of
      novel therapies for (micro- or macro-) metastatic osteosarcoma that improve
      survival and might ultimately lead to a cure in both species. 

PMID- 24924179
TI  - Oncolytic viruses for potential osteosarcoma therapy.
AB  - Since the first anecdotal reports of dramatic tumor responses following a viral
      infection in early 1900s, the field of oncolytic virotherapy has evolved at a
      rapid pace finally making its way into clinical trials. A large number of both
      wild-type and genetically altered viruses with a preferential replication
      competency for tumor cells have been studied in tissue cultures, animal models
      and in humans, with an ever increasing repertoire of new viruses being added to
      this pool. Although oncolytic viruses have caused dramatic antitumor responses in
      cell cultures and mouse models, their clinical effects in humans have been
      modest. Therefore, the current research is focused on understanding the
      mechanisms by which viruses kill tumor cells, the barriers to successful viral
      delivery and penetration into tumor cells, the role of the immune system in viral
      oncolysis and generating stronger target specific and replication competent
      viruses. Osteosarcoma is a challenging malignancy to identify novel targets for
      therapy due to its complex genetic make-up. Oncolytic virotherapy may be a
      promising approach as a novel therapeutic, not dependent on consistent expression
      of a single target. In this review we summarize the supportive evidence and
      rationale for use of viral oncolysis in osteosarcoma along with the specific
      challenges it may face. 

PMID- 24924180
TI  - IL-11Ralpha: a novel target for the treatment of osteosarcoma.
AB  - Recent advances have shown that cell surface receptors are expressed
      differentially in normal and pathological conditions. Novel organ specific and
      disease specific proteins expressed on tumor vasculature have been identified by
      in vivo phage display technology and the diversity of the tumor-associated
      vasculature has provided the basis for the development of targeted therapeutics.
      Investigators recently screened a phage display library in a human cancer
      patient. An IL-11 mimic phage displaying the cyclic peptide CGRRAGGSC (single
      letter amino acid code) specifically bound to immobilized IL-11Ralpha. It has
      been demonstrated that the expression of the IL-11Ralpha is increased in several
      other types of tumors including osteosarcoma. The ability to selectively target
      the IL-11Ralpha may provide an alternative treatment of for a disease where new
      treatment options are truly needed. 

PMID- 24924181
TI  - Bone-seeking radiopharmaceuticals as targeted agents of osteosarcoma: samarium
      153-EDTMP and radium-223.
AB  - Osteosarcoma is a cancer characterized by formation of bone by malignant cells.
      Routine bone scan imaging with Tc-99m-MDP is done at diagnosis to evaluate
      primary tumor uptake and check for bone metastases. At time of relapse the Tc-99m
      MDP bone scan also provides a specific means to assess formation of bone by
      malignant osteosarcoma cells and the potential for bone-seeking
      radiopharmaceuticals to deliver radioactivity directly into osteoblastic
      osteosarcoma lesions. This chapter will review and compare a bone-seeking
      radiopharmaceutical that emits beta-particles, samarium-153-EDTMP, with an alpha
      particle emitter, radium-223. The charged alpha particles from radium-223 have
      far more mass and energy than beta particles (electrons) from Sm-153-EDTMP.
      Because radium-223 has less marrow toxicity and more radiobiological
      effectiveness, especially if inside the bone forming cancer cell than samarium
      153-EDTMP, radium-223 may have greater potential to become widely used against
      osteosarcoma as a targeted therapy. Radium-223 also has more potential to be used
      with chemotherapy against osteosarcoma and bone metastases. Because osteosarcoma
      makes bone and radium-223 acts like calcium, this radiopharmaceutical could
      possibly become a new targeted means to achieve safe and effective reduction of
      tumor burden as well as facilitate better surgery and/or radiotherapy for
      difficult to resect large, or metastatic tumors. 

PMID- 24924182
TI  - Muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE)
      in the treatment of osteosarcoma.
AB  - Bacille Calmette-Guerin (BCG) has been used for decades as an immune stimulant to
      treat cancer. Early work by Fidler and Kleinerman identified muramyl dipeptide
      (MDP) as a critical component of the BCG cell wall which retained most of the
      immunostimulatory properties of the native BCG. Addition of a peptide to MDP
      resulted in muramyl tripeptide (MTP) which allowed incorporation into liposomal
      membranes. The resulting pharmaceutical, liposomal muramyl tripeptide
      phosphatidyl ethanolamine (L-MTP-PE or mifamurtide) showed activity in
      preclinical models of human cancers. Phase I studies documented the safety of the
      compound for human administration. These trials did not reach a maximally
      tolerated dose (MTD), and the dose chosen for phase II trials was a biologically
      optimized dose, not an MTD. Phase II studies showed decreased risk of further
      recurrence in patients who received mifamurtide after surgical ablation of
      metastatic osteosarcoma. A phase III prospective randomized trial demonstrated a
      statistically significant reduction in the risk of death from osteosarcoma when
      MTP was added to systemic chemotherapy for the treatment of localized
      osteosarcoma. The same trial allowed treatment of patients who presented with
      initially metastatic disease. While the overall and event-free survival was
      improved in patients with metastatic osteosarcoma who received L-MTP-PE, the
      sample size was small and the improvement did not achieve conventional
      statistical significance. From 2008 to 2012, patients with metastatic and
      recurrent osteosarcoma were given L-MTP-PE in an expanded access trial, and the
      results suggest a decreased risk of subsequent recurrence and death with the
      inclusion of L-MTP-PE in the treatment strategy for these high-risk patients. 

PMID- 24924184
TI  - Natural killer cells for osteosarcoma.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that have
      the ability to recognize malignant cells through detection of a variety of cell
      surface indicators of stress and danger. Once activated through such recognition,
      NK cells release cytokines and induce target cell lysis through a variety of
      mechanisms. NK cells are increasingly recognized as important mediators of other
      immunotherapeutic modalities, including cytokines, antibodies, immunomodulators,
      and stem cell transplantation. Adoptive immunotherapies with NK cells are being
      tested in early-stage clinical trials, and recent advances in manipulating their
      number and function have caused a renewed emphasis on this cancer-fighting cell.
      In this chapter we address the evidence for NK cell recognition of osteosarcoma
      in vitro and in vivo, discuss new therapies that are directly or indirectly
      dependent on NK cell function, and describe potential approaches for manipulating
      NK cell number and function to enhance therapy against osteosarcoma. 

PMID- 24924185
TI  - Hybridizing triboelectrification and electromagnetic induction effects for high
      efficient mechanical energy harvesting.
AB  - The recently introduced triboelectric nanogenerator (TENG) and the traditional
      electromagnetic induction generator (EMIG) are coherently integrated in one
      structure for energy harvesting and vibration sensing/isolation. The suspended
      structure is based on two oppositely oriented magnets that are enclosed by hollow
      cubes surrounded with coils, which oscillates in response to external disturbance
      and harvests mechanical energy simultaneously from triboelectrification and
      electromagnetic induction. It extends the previous definition of hybrid cell to
      harvest the same type of energy with multiple approaches. Both the sliding-mode
      TENG and contact-mode TENG can be achieved in the same structure. In order to
      make the TENG and EMIG work together, transformers are used to match the output
      impedance between these two power sources with very different characteristics.
      The maximum output power of 7.7 and 1.9 mW on the same load of 5 kOmega was
      obtained for the TENG and EMIG, respectively, after impedance matching.
      Benefiting from the rational design, the output signal from the TENG and the EMIG
      are in phase. They can be added up directly to get an output voltage of 4.6 V and
      an output current of 2.2 mA in parallel connection. A power management circuit
      was connected to the hybrid cell, and a regulated voltage of 3.3 V with constant
      current was achieved. For the first time, a logic operation was carried out on a
      half-adder circuit by using the hybrid cell working as both the power source and
      the input digit signals. We also demonstrated that the hybrid cell can serve as a
      vibration isolator. Further applications as vibration dampers, triggers, and
      sensors are all promising. 

PMID- 24924183
TI  - Genetically modified T-cell therapy for osteosarcoma.
AB  - T-cell immunotherapy may offer an approach to improve outcomes for patients with
      osteosarcoma, who fail current therapies. In addition, it has the potential to
      reduce treatment-related complications for all patients. Generating tumor
      specific T cells with conventional antigen presenting cells ex vivo is time
      consuming and often results in T-cell products with a low frequency of tumor
      specific T cells. In addition, the generated T cells remain sensitive to the
      immunosuppressive tumor microenvironment. Genetic modification of T cells is one
      strategy to overcome these limitations. For example, T cells can be genetically
      modified to render them antigen specific, resistant to inhibitory factors, or
      increase their ability to home to tumor sites. Most genetic modification
      strategies have only been evaluated in preclinical models, however early phase
      clinical trials are in progress. In this chapter we review the current status of
      gene-modified T-cell therapy with special focus on osteosarcoma, highlighting
      potential antigenic targets, preclinical and clinical studies, and strategies to
      improve current T-cell therapy approaches. 

PMID- 24924186
TI  - A mutation burst during the acute phase of Helicobacter pylori infection in
      humans and rhesus macaques.
AB  - The evolution rate and genetic changes that occur during chronic infection with
      Helicobacter pylori have been analysed, but little is known about the genomic
      changes during the initial, acute bacterial infection phase. Here we analyse the
      rate and pattern of genome evolution in H. pylori from the genomes of two input
      strains isolated from human volunteers with asymptomatic infection, and the
      genomes of two output strains collected 20 and 44 days after re-infection.
      Similarly, we analyse genome evolution in bacteria from the genome sequences of
      input and output strains sequentially taken after experimental infection of a
      rhesus macaque. The estimated mutation rate reveals a mutation burst during the
      acute infection phase that is over 10 times faster than the mutation rate during
      chronic infection, and orders of magnitude faster than mutation rates in any
      other bacteria. The elevated frequency of mutations in outer membrane protein
      genes suggests that the mutation burst facilitates rapid host adaptation of the
      bacteria. 

PMID- 24924187
TI  - Sugar-based molecular computing by material implication.
AB  - A method to integrate an (in principle) unlimited number of molecular logic gates
      to construct complex circuits is presented. Logic circuits, such as half- or full
      adders, can be reinterpreted by using the functional completeness of the
      implication function (IMP) and the trivial FALSE operation. The molecular gate
      IMP is represented by a fluorescent boronic acid sugar probe. An external wiring
      algorithm translates the fluorescent output from one gate into a chemical input
      for the next gate on microtiter plates. This process is demonstrated on a four
      bit full adder. 

PMID- 24924188
TI  - Ganges River dolphin: an overview of biology, ecology, and conservation status in
      India.
AB  - Ganges River dolphin, Platanista gangetica gangetica, is one of the three
      obligatory freshwater dolphins in the world and is distributed in the Ganges
      Brahmaputra-Meghna and Sangu-Karnaphuli River systems in India, Nepal, and
      Bangladesh. This species is facing considerable threats to its survival, and its
      population has dwindled from 4000 to 5000 in the early 1980s to 3500 in 2014 in
      the distribution range. This article reviews current status of the sub-species,
      habitat use, and the potential threats that the dolphins face for their survival
      (details of taxonomic status and genetics, evolutionary adaptations and
      anatomical peculiarities, physical adaptation, primitive characteristics,
      biology, behavior, surfacing behavior and dive times, mating and birth, and life
      span/age have been placed as Electronic Supplementary Materials). Recommendations
      have been made for the protection and developing strategies for the conservation
      of this Endangered and endemic sub-species. 

PMID- 24924189
TI  - Small interfering RNA inhibition of Andes virus replication.
AB  - Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary
      syndrome (HPS) in the Americas, and is the only hantavirus associated with human
      to-human transmission. Case fatality rates of ANDV-induced HPS are approximately
      40%. There are currently no effective vaccines or antivirals against ANDV. Since
      HPS severity correlates with viral load, we tested small interfering RNA (siRNA)
      directed against ANDV genes as a potential antiviral strategy. We designed pools
      of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested
      their efficacy in reducing viral replication in vitro. The siRNA pool targeting
      the S segment reduced viral transcription and replication in Vero-E6 cells more
      efficiently than those targeting the M and L segments. In contrast, siRNAs
      targeting the S, M, or L segment were similar in their ability to reduce viral
      replication in human lung microvascular endothelial cells. Importantly, these
      siRNAs inhibit ANDV replication even if given after infection. Taken together,
      our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit
      ANDV replication, and show promise as a strategy for developing therapeutics
      against ANDV infection. 

PMID- 24924190
TI  - The microRNA bantam regulates a developmental transition in epithelial cells that
      restricts sensory dendrite growth.
AB  - As animals grow, many early born structures grow by cell expansion rather than
      cell addition; thus growth of distinct structures must be coordinated to maintain
      proportionality. This phenomenon is particularly widespread in the nervous
      system, with dendrite arbors of many neurons expanding in concert with their
      substrate to sustain connectivity and maintain receptive field coverage as
      animals grow. After rapidly growing to establish body wall coverage, dendrites of
      Drosophila class IV dendrite arborization (C4da) neurons grow synchronously with
      their substrate, the body wall epithelium, providing a system to study how
      proportionality is maintained during animal growth. Here, we show that the
      microRNA bantam (ban) ensures coordinated growth of C4da dendrites and the
      epithelium through regulation of epithelial endoreplication, a modified cell
      cycle that entails genome amplification without cell division. In Drosophila
      larvae, epithelial endoreplication leads to progressive changes in dendrite
      extracellular matrix (ECM) and dendrite-epithelium contacts, coupling
      dendrite/substrate expansion and restricting dendrite growth beyond established
      boundaries. Moreover, changes in epithelial expression of cell adhesion
      molecules, including the beta-integrin myospheroid (mys), accompany this
      developmental transition. Finally, endoreplication and the accompanying changes
      in epithelial mys expression are required to constrain late-stage dendrite growth
      and structural plasticity. Hence, modulating epithelium-ECM attachment probably
      influences substrate permissivity for dendrite growth and contributes to the
      dendrite-substrate coupling that ensures proportional expansion of the two cell
      types. 

PMID- 24924191
TI  - FGF signaling activates a Sox9-Sox10 pathway for the formation and branching
      morphogenesis of mouse ocular glands.
AB  - Murine lacrimal, harderian and meibomian glands develop from the prospective
      conjunctival and eyelid epithelia and produce secretions that lubricate and
      protect the ocular surface. Sox9 expression localizes to the presumptive
      conjunctival epithelium as early as E11.5 and is detected in the lacrimal and
      harderian glands as they form. Conditional deletion showed that Sox9 is required
      for the development of the lacrimal and harderian glands and contributes to the
      formation of the meibomian glands. Sox9 regulates the expression of Sox10 to
      promote the formation of secretory acinar lobes in the lacrimal gland. Sox9 and
      FGF signaling were required for the expression of cartilage-associated
      extracellular matrix components during early stage lacrimal gland development.
      Fgfr2 deletion in the ocular surface epithelium reduced Sox9 and eliminated Sox10
      expression. Sox9 deletion from the ectoderm did not affect Fgf10 expression in
      the adjacent mesenchyme or Fgfr2 expression in the epithelium, but appeared to
      reduce FGF signaling. Sox9 heterozygotes showed a haploinsufficient phenotype, in
      which the exorbital branch of the lacrimal gland was absent in most cases.
      However, enhancement of epithelial FGF signaling by expression of a
      constitutively active FGF receptor only partially rescued the lacrimal gland
      defects in Sox9 heterozygotes, suggesting a crucial role of Sox9, downstream of
      FGF signaling, in regulating lacrimal gland branching and differentiation. 

PMID- 24924192
TI  - Large hypomethylated domains serve as strong repressive machinery for key
      developmental genes in vertebrates.
AB  - DNA methylation is a fundamental epigenetic modification in vertebrate genomes
      and a small fraction of genomic regions is hypomethylated. Previous studies have
      implicated hypomethylated regions in gene regulation, but their functions in
      vertebrate development remain elusive. To address this issue, we generated
      epigenomic profiles that include base-resolution DNA methylomes and histone
      modification maps from both pluripotent cells and mature organs of medaka fish
      and compared the profiles with those of human ES cells. We found that a subset of
      hypomethylated domains harbor H3K27me3 (K27HMDs) and their size positively
      correlates with the accumulation of H3K27me3. Large K27HMDs are conserved between
      medaka and human pluripotent cells and predominantly contain promoters of
      developmental transcription factor genes. These key genes were found to be under
      strong transcriptional repression, when compared with other developmental genes
      with smaller K27HMDs. Furthermore, human-specific K27HMDs show an enrichment of
      neuronal activity-related genes, which suggests a distinct regulation of these
      genes in medaka and human. In mature organs, some of the large HMDs become
      shortened by elevated DNA methylation and associate with sustained gene
      expression. This study highlights the significance of domain size in epigenetic
      gene regulation. We propose that large K27HMDs play a crucial role in pluripotent
      cells by strictly repressing key developmental genes, whereas their shortening
      consolidates long-term gene expression in adult differentiated cells. 

PMID- 24924193
TI  - The dynamic DNA methylation cycle from egg to sperm in the honey bee Apis
      mellifera.
AB  - In honey bees (Apis mellifera), the epigenetic mark of DNA methylation is central
      to the developmental regulation of caste differentiation, but may also be
      involved in additional biological functions. In this study, we examine the whole
      genome methylation profiles of three stages of the haploid honey bee genome:
      unfertilised eggs, the adult drones that develop from these eggs and the sperm
      produced by these drones. These methylomes reveal distinct patterns of
      methylation. Eggs and sperm show 381 genes with significantly different CpG
      methylation patterns, with the vast majority being more methylated in eggs. Adult
      drones show greatly reduced levels of methylation across the genome when compared
      with both gamete samples. This suggests a dynamic cycle of methylation loss and
      gain through the development of the drone and during spermatogenesis. Although
      fluxes in methylation during embryogenesis may account for some of the
      differentially methylated sites, the distinct methylation patterns at some genes
      suggest parent-specific epigenetic marking in the gametes. Extensive germ line
      methylation of some genes possibly explains the lower-than-expected frequency of
      CpG sites in these genes. We discuss the potential developmental and evolutionary
      implications of methylation in eggs and sperm in this eusocial insect species. 

PMID- 24924194
TI  - Transcription factors involved in retinogenesis are co-opted by the circadian
      clock following photoreceptor differentiation.
AB  - The circadian clock is known to regulate a wide range of physiological and
      cellular processes, yet remarkably little is known about its role during embryo
      development. Zebrafish offer a unique opportunity to explore this issue, not only
      because a great deal is known about key developmental events in this species, but
      also because the clock starts on the very first day of development. In this
      study, we identified numerous rhythmic genes in zebrafish larvae, including the
      key transcriptional regulators neurod and cdx1b, which are involved in neuronal
      and intestinal differentiation, respectively. Rhythmic expression of neurod and
      several additional transcription factors was only observed in the developing
      retina. Surprisingly, these rhythms in expression commenced at a stage of
      development after these transcription factors are known to have played their
      essential role in photoreceptor differentiation. Furthermore, this circadian
      regulation was maintained in adult retina. Thus, once mature photoreceptors are
      formed, multiple retinal transcription factors fall under circadian clock
      control, at which point they appear to play a new and important role in
      regulating rhythmic elements in the phototransduction pathway. 

PMID- 24924195
TI  - Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle
      stem/progenitor cells.
AB  - The transition between the proliferation and differentiation of progenitor cells
      is a key step in organogenesis, and alterations in this process can lead to
      developmental disorders. The extracellular signal-regulated kinase 1/2 (ERK)
      signaling pathway is one of the most intensively studied signaling mechanisms
      that regulates both proliferation and differentiation. How a single molecule
      (e.g. ERK) can regulate two opposing cellular outcomes is still a mystery. Using
      both chick and mouse models, we shed light on the mechanism responsible for the
      switch from proliferation to differentiation of head muscle progenitors and
      implicate ERK subcellular localization. Manipulation of the fibroblast growth
      factor (FGF)-ERK signaling pathway in chick embryos in vitro and in vivo
      demonstrated that blockage of this pathway accelerated myogenic differentiation,
      whereas its activation diminished it. We next examined whether the spatial
      subcellular localization of ERK could act as a switch between proliferation
      (nuclear ERK) and differentiation (cytoplasmic ERK) of muscle progenitors. A
      myristoylated peptide that blocks importin 7-mediated ERK nuclear translocation
      induced robust myogenic differentiation of muscle progenitor/stem cells in both
      head and trunk. In the mouse, analysis of Sprouty mutant embryos revealed that
      increased ERK signaling suppressed both head and trunk myogenesis. Our findings,
      corroborated by mathematical modeling, suggest that ERK shuttling between the
      nucleus and the cytoplasm provides a switch-like transition between proliferation
      and differentiation of muscle progenitors. 

PMID- 24924196
TI  - Larval mesenchyme cell specification in the primitive echinoid occurs
      independently of the double-negative gate.
AB  - Echinoids (sea urchins) are divided into two major groups - cidaroids (a
      'primitive' group) and euechinoids (a 'derived' group). The cidaroids are a
      promising model species for understanding the ancestral developmental mechanisms
      in echinoids, but little is known about the molecular mechanisms of cidaroid
      development. In euechinoids, skeletogenic mesenchyme cell specification is
      regulated by the double-negative gate (DNG), in which hesC represses the
      transcription of the downstream mesenchyme specification genes (alx1, tbr and
      ets1), thereby defining the prospective mesenchyme region. To estimate the
      ancestral mechanism of larval mesenchyme cell specification in echinoids, the
      expression patterns and roles of mesenchyme specification genes in the cidaroid
      Prionocidaris baculosa were examined. The present study reveals that the
      expression pattern and function of hesC in P. baculosa were inconsistent with the
      DNG model, suggesting that the euechinoid-type DNG is not utilized during
      cidaroid mesenchyme specification. In contrast with hesC, the expression patterns
      and functions of alx1, tbr and ets1 were similar between P. baculosa and
      euechinoids. Based on these results, we propose that the roles of alx1, tbr and
      ets1 in mesenchyme specification were established in the common ancestor of
      echinoids, and that the DNG system was acquired in the euechinoid lineage after
      divergence from the cidaroid ancestor. The evolutionary timing of the
      establishment of the DNG suggests that the DNG was originally related to
      micromere and/or primary mesenchyme cell formation but not to skeletogenic cell
      differentiation. 

PMID- 24924198
TI  - A conserved transcriptional network regulates lamina development in the
      Drosophila visual system.
AB  - The visual system of insects is a multilayered structure composed externally by
      the compound eye and internally by the three ganglia of the optic lobe: lamina,
      medulla and the lobula complex. The differentiation of lamina neurons depends
      heavily on Hedgehog (Hh) signaling, which is delivered by the incoming
      photoreceptor axons, and occurs in a wave-like fashion. Despite the primary role
      of lamina neurons in visual perception, it is still unclear how these neurons are
      specified from neuroepithelial (NE) progenitors. Here we show that a homothorax
      (hth)-eyes absent (eya)-sine oculis (so)-dachshund (dac) gene regulatory cassette
      is involved in this specification. Lamina neurons differentiate from NE
      progenitors that express hth, eya and so. One of the first events in the
      differentiation of lamina neurons is the upregulation of dac expression in
      response to Hh signaling. We show that this dac upregulation, which marks the
      transition from NE progenitors into lamina precursors, also requires Eya/So, the
      expression of which is locked in by mutual feedback. dac expression is crucial
      for lamina differentiation because it ensures repression of hth, a negative
      regulator of single-minded, and thus dac allows further lamina neuron
      differentiation. Therefore, the specification of lamina neurons is controlled by
      coupling the cell-autonomous hth-eya-so-dac regulatory cassette to Hh signaling. 

PMID- 24924197
TI  - A transcription factor network specifying inhibitory versus excitatory neurons in
      the dorsal spinal cord.
AB  - The proper balance of excitatory and inhibitory neurons is crucial for normal
      processing of somatosensory information in the dorsal spinal cord. Two neural
      basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have
      contrasting functions in specifying these neurons. To understand how Ascl1 and
      Ptf1a function in this process, we identified their direct transcriptional
      targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA
      Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that
      specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly
      regulates genes with roles in several steps of the neurogenic program, including
      Notch signaling, neuronal differentiation, axon guidance and synapse formation.
      By contrast, Ptf1a directly regulates genes encoding components of the
      neurotransmitter machinery in inhibitory neurons, and other later aspects of
      neural development distinct from those regulated by Ascl1. Moreover, Ptf1a
      represses the excitatory neuronal fate by directly repressing several targets of
      Ascl1. Ascl1 and Ptf1a bind sequences primarily enriched for a specific E-Box
      motif (CAGCTG) and for secondary motifs used by Sox, Rfx, Pou and homeodomain
      factors. Ptf1a also binds sequences uniquely enriched in the CAGATG E-box and in
      the binding motif for its co-factor Rbpj, providing two factors that influence
      the specificity of Ptf1a binding. The direct transcriptional targets identified
      for Ascl1 and Ptf1a provide a molecular understanding of how these DNA-binding
      proteins function in neuronal development, particularly as key regulators of
      homeodomain TFs required for neuronal subtype specification. 

PMID- 24924199
TI  - Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer.
AB  - Triple-negative breast cancers (TNBCs) have poor clinical outcomes owing to a
      lack of targeted therapies. Activation of the MEK/MAPK pathway in TNBC has been
      associated with resistance to conventional chemotherapy and biologic agents and
      has a significant role in poor clinical outcomes. NV1066, a replication-competent
      herpes virus, infected, replicated in and killed all TNBC cell lines (MDA-MB-231,
      HCC1806, HCC38, HCC1937, HCC1143) tested. Greater than 90% cell kill was achieved
      in more-sensitive lines (MDA-MB-231, HCC1806, HCC38) by day 6 at a multiplicity
      of infection (MOI) of 0.1. In less-sensitive lines (HCC1937, HCC1143), NV1066
      still achieved >70% cell kill by day 7 (MOI 1.0). In vivo, mean volume of flank
      tumors 14 days after treatment with NV1066 was 57 versus 438 mm(3) in controls
      (P=0.002). NV1066 significantly downregulated p-MAPK activation by 48 h in all
      cell lines in vitro and in MDA-MB-231 xenografts in vivo. NV1066 demonstrated
      synergistic effects with a MEK inhibitor, PD98059 in vitro. We demonstrate that
      oncolytic viral therapy (NV1066) effectively treats TNBC with correlation to
      decreased MEK/MAPK signaling. These findings merit future studies investigating
      the potential role of NV1066 as a sensitizing agent for conventional
      chemotherapeutic and biologic agents by downregulating the MAPK signaling
      pathway.

PMID- 24924200
TI  - Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to
      tamoxifen through upregulation of TIMP3.
AB  - Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It
      is still unclear if and how miRNAs-221/222 are implicated in breast cancer and
      the resistance to estrogen receptor modulator tamoxifen. We investigated the
      roles and mechanisms of miR-221/222 in breast cancer cells, particularly in
      modulating response to tamoxifen therapy. MCF-7 and MDA-MB-231 breast cancer
      cells were transfected with antisense oligonucleotides AS-miR-221 and AS-miR-222
      and their expression of miR-221 and miR-222 was assessed. The correlation of miR
      221/222 with tissue inhibitor of metalloproteinase-3 (TIMP3) expression was
      investigated by fluorescence quantitative PCR and western blotting analysis. The
      therapeutic sensitivity of these cells, transfected and untransfected, to
      tamoxifen was determined. Transfection of AS-miR-221 and AS-miR-222 dramatically
      inhibited expression of miR-221 and miR-222, respectively, in both MCF-7 and MDA
      MB-231 cells (P<0.05-0.01). Downregulation of miR-221/222 significantly increased
      the expression of TIMP3 compared with controls (P<0.05-0.01). The viability of
      estrogen receptor (ER)-positive MCF-7 cells transfected with AS-miR-221 or/and AS
      miR-222 was significantly reduced by tamoxifen (P<0.05-0.01). We have
      demonstrated for the first time that suppression of miRNA-221/222 increases the
      sensitivity of ER-positive MCF-7 breast cancer cells to tamoxifen. This effect is
      mediated through upregulation of TIMP3. These findings suggest that upregulation
      of TIMP3 via inhibition of miRNA-221/222 could be a promising therapeutic
      approach for breast cancer. 

PMID- 24924202
TI  - Reduction in Renal Specimen After Laparoscopic Radical Nephrectomy: A
      Histopathologic Analysis.
AB  - Abstract Background and Purpose: There is no consensus on the most appropriate
      way to extract the kidney after laparoscopy. A previous study evaluated the
      reduction in total kidney volume and incision size (40%) after perfusion with a
      5% hypertonic solution in a porcine model. The purpose of the current study was
      to compare the histopathologic renal tumor diagnosis before and after this
      perfusion. Furthermore, fluid drained from the renal vein was analyzed for the
      presence of neoplastic cells. Materials and Methods: After radical nephrectomy,
      specimens of 21 cases of renal tumors were studied. A small piece of the tumor
      was removed and fixed in formaldehyde. After that, 500 mL of a 5% NaCL solution
      was infused through the renal artery. The first 10 mL drained from the vein was
      collected and sent for cytologic study. The specimens and the fragment were
      analyzed. The parameters studied were histologic subtypes, Fuhrman grade,
      necrosis, and microvascular invasion. Results: Clear-cell renal carcinoma was
      found in 81% of the cases. Two cases of chromophobic renal carcinoma, one case of
      papillary tumor, and one case of oncocytoma were found. There were no differences
      in histologic subtypes, Fuhrman grade, necrosis, and microvascular invasion
      before and after perfusion in most of the cases. All cytologic analysis of
      drained liquid from the renal vein was negative for neoplastic cells.
      Conclusions: Renal perfusion with 5% NaCL solution after laparoscopic radical
      nephrectomy did not interfere with the histopathologic and cytologic
      characteristics of the kidney. In addition, all samples from the liquid drained
      from the renal vein were negative for neoplastic cells. These findings suggest
      that renal shrinkage with hypertonic saline after laparoscopic radical
      nephrectomy is feasible and might be useful for patients with kidney cancer.
      Validation of our results as well as their impact on clinical outcomes is
      warranted.

PMID- 24924201
TI  - EMMPRIN reduction via scFv-M6-1B9 intrabody affects alpha3beta1-integrin and MCT1
      functions and results in suppression of progressive phenotype in the colorectal
      cancer cell line Caco-2.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) exhibits overexpression
      in various cancers and promotes cancer progression and metastasis via the
      interaction with its associated molecules. The scFv-M6-1B9 intrabody has a
      potential ability to reduce EMMPRIN cell surface expression. However, the
      subsequent effect of scFv-M6-1B9 intrabody-mediated EMMPRIN abatement on its
      related molecules, alpha3beta1-integrin, MCT1, MMP-2 and MMP-9, is undefined. Our
      results demonstrated that the scFv-M6-1B9 intrabody efficiently decreased
      alpha3beta1-integrin cell surface expression levels. In addition, intracellular
      accumulation of MCT1 and lactate were increased. These results lead to
      suppression of features characteristic for tumor progression, including cell
      migration, proliferation and invasion, in a colorectal cancer cell line (Caco-2)
      although there was no difference in MMP expression. Thus, EMMPRIN represents an
      attractive target molecule for the disruption of cancer proliferation and
      metastasis. An scFv-M6-1B9 intrabody-based approach could be relevant for cancer
      gene therapy. 

PMID- 24924204
TI  - Reinforcement signals facilitate learning about early behaviors of a response
      sequence.
AB  - The present experiment examined the effect of presenting a stimulus
      simultaneously with the delivery of reinforcement on the acquisition of a two
      response sequence. Two groups of rats responded on a schedule that required the
      subject to emit either a left-lever right-lever or a right-lever left-lever
      response sequence to obtain reinforcement. A group with a 500-ms auditory
      reinforcement-signal emitted the sequence at a higher rate than a groups of rats
      that lacked the signal. The rates of response on the terminal response lever were
      similar in both signalled and unsignalled groups, but rates were higher on the
      initial response lever in the signalled compared to the unsignalled condition.
      These results suggest that a signal for reinforcement acts to enhance learning
      about the preceding response sequence, and that this facilitation is due to an
      enhancement in emitting the initial rather than the terminal component of the
      sequence. 

PMID- 24924205
TI  - Description des donnees d'observation continue du comportement par une technique
      d'analyse de textes 1. Mise enevidence de styles individuels de maternage dans
      une lignee consanguine de souris.
AB  - This study illustrates the use of an original technique to give a precise
      description of the developmental environment provided by female mice to their
      pups, and of his changes with the age of the pups. Successive events recorded by
      continous observation of maternal behaviour of C57BL/6 inbred mice were analysed
      by a technique devoted to textual analysis. The different mothers were easily
      characterised by differences in the frequencies of the behavioural items
      expressed on the nest. These individual differences were stable with increasing
      age of the pups. On the other hand, the frequencies of behavioural sequences
      showed differences related to the age of the pups. The psychological meaning of
      some behavioural items is suggested by the results. The relevance of multivariate
      techniques of description directly applied on initial data of continous
      observation is discussed. 

PMID- 24924203
TI  - Mechanisms of tolerance and high degradation capacity of the herbicide mesotrione
      by Escherichia coli strain DH5-alpha.
AB  - The intensive use of agrochemicals has played an important role in increasing
      agricultural production. One of the impacts of agrochemical use has been changes
      in population structure of soil microbiota. The aim of this work was to analyze
      the adaptive strategies that bacteria use to overcome oxidative stress caused by
      mesotrione, which inhibits 4-hydroxyphenylpyruvate dioxygenase. We also examined
      antioxidative stress systems, saturation changes of lipid membranes, and the
      capacity of bacteria to degrade mesotrione. Escherichia coli DH5-a was chosen as
      a non-environmental strain, which is already a model bacterium for studying
      metabolism and adaptation. The results showed that this bacterium was able to
      tolerate high doses of the herbicide (10* field rate), and completely degraded
      mesotrione after 3 h of exposure, as determined by a High Performance Liquid
      Chromatography. Growth rates in the presence of mesotrione were lower than in the
      control, prior to the period of degradation, showing toxic effects of this
      herbicide on bacterial cells. Changes in the saturation of the membrane lipids
      reduced the damage caused by reactive oxygen species and possibly hindered the
      entry of xenobiotics in the cell, while activating glutathione-S-transferase
      enzyme in the antioxidant system and in the metabolizing process of the
      herbicide. Considering that E. coli DH5-alpha is a non-environmental strain and
      it had no previous contact with mesotrione, the defense system found in this
      strain could be considered non-specific. This bacterium system response may be a
      general adaptation mechanism by which bacterial strains resist to damage from the
      presence of herbicides in agricultural soils. 

PMID- 24924206
TI  - Description des donnees d'observation continue du comportement par une technique
      d'analyse de textes. 2. Comparaisons des conduites maternelles dans trois souches
      de souris.
AB  - This study illustrates the use of multifactorial analysis to perform comparisons
      between different genotypic groups, based on behavioral profiles. Maternal
      behaviour of C57BL/6 mice and of two reciprocal F2 was precisely described by
      continous observation. Unpolished data were directly analysed by a textual
      analysis technique using correspondences analysis. Strains were clearly different
      according to the relative frequencies of the different acts. These differences
      seemed to be related to grand-maternal effects, as previously shown in the same
      strains. Pups age related variation between day 2 and day 6 was very low when
      compared to maternal styles of the three strains. 

PMID- 24924207
TI  - Species-specific sound production in three ephippigerine bushcrickets.
AB  - Songs of three Ephippigerine species (Ephippiger ephippiger, E. discoidalis and
      E.perforatus) have been recorded and analysed. Manipulation experiments have been
      carried out by removing single teeth from the pars stridens. The songs of
      manipulated animals show characteristic gaps within the impulse structure of the
      opening and closing syllables. Morphological measurements were carried out by
      means of SEM-photographs of the pars stridens. Combining both the bioacoustic and
      morphological results reveals that only the lateral part of the pars stridens is
      used during stridulation. Furthermore it could be shown that the individual
      impulse interval pattern within one syllable is also highly constant between
      syllables. The impulse interval pattern correlates with the pattern of tooth
      spacing on the pars stridens. 

PMID- 24924208
TI  - The spatial parameters encoded by hamsters during exploration: a further study.
AB  - The information used by hamsters while reacting to a spatial change after
      habituation of exploration was analysed. In our previous work, animals had the
      opportunity to explore a circular open field containing four different objects,
      for two sessions. During the third session, when the locations of two objects
      were exchanged, hamsters re-explored selectively the exchanged objects. The
      present study, relying on the same procedure, examined the possibility that
      subjects' detection of the change relied on an egocentric strategy, i.e., that
      hamsters were using the pattern formed by the horizontal alignment of the objects
      as seen from the location at which they were introduced into the field.
      Therefore, in Experiment 1, the placement of the subjects at the beginning of the
      test session was different from that used on previous sessions. Most hamsters
      still displayed a reaction to the object displacements, although their reactions
      were not selectively directed to the exchanged objects. Experiment 2 revealed
      that, when the subjects were placed at a different location at the beginning of
      each session, the change in object locations was not detected. Lastly, Experiment
      3 showed that removing the only available extra-apparatus visual cue did not
      prevent hamsters from selectively reacting to the displaced objects. These
      results are discussed with respect to the notion that during exploration hamsters
      encode local views of the environment, which ultimately leads to the building up
      of overall cognitive maps after they have been given sufficient exploration. 

PMID- 24924209
TI  - Biomonitoring of infant exposure to phenolic endocrine disruptors using urine
      expressed from disposable gel diapers.
AB  - Infant exposure to endocrine disruptors (EDs) may cause adverse health effects
      because of their fast growth and development during this life stage. However,
      collecting urine from infants for exposure assessment using biological monitoring
      is not an easy task. For this purpose, we evaluated the feasibility of using
      urine expressed from disposable gel absorbent diapers (GADs) as a matrix for
      biomonitoring selected phenolic EDs. GADs urine was expressed with the assistance
      of CaCl(2) and was collected using a device fabricated in our laboratory. The
      analytes were extracted and concentrated using a liquid-liquid method and their
      hydroxyl groups were modified by dansyl chloride to enhance their chromatography
      and detection. Finally, the analytes were measured by high-performance liquid
      chromatography (HPLC) coupled with electrospray ionization (ESI) tandem mass
      spectrometry (MS/MS). The target chemicals were bisphenol A, triclosan, 17 alpha
      ethynylestradiol, the natural hormone estrone, and 17 beta-estradiol. The ratio
      of the CaCl(2) to the urine-wetted gel absorbent, variation of the inter
      urination volume, and analyte deposition bias in the diaper were assessed.
      Analyte blank values in the diapers, the sample storage stabilities, and
      recoveries of the analytes were also evaluated. The results showed that 70-80 %
      of the urine could be expressed from the diaper with the assistance of CaCl(2)
      and 70.5-124 % of the spiked analytes can be recovered in the expressed urine.
      The limits of detections (LODs) were 0.02-0.27 ng/mL, well within the range for
      detection in human populations. Our pilot data suggest that infants are widely
      exposed to the selected EDs.

PMID- 24924210
TI  - Monitoring urinary metabolites resulting from sulfur mustard exposure in rabbits,
      using highly sensitive isotope-dilution gas chromatography-mass spectrometry.
AB  - A highly sensitive method for the determination of sulfur mustard (SM)
      metabolites thiodiglycol (TDG) and thiodiglycol sulfoxide (TDGO) in urine was
      established and validated using isotope-dilution negative-ion chemical ionization
      (NICI) gas chromatography-mass spectrometry (GC-MS). TDGO in the samples was
      reduced with TiCl3, and then determined together with TDG as a single analyte.
      The sample preparation procedures, including two solid-phase-extraction (SPE)
      clean-up steps, were optimized to improve the sensitivity of the method. The
      limits of detection (LOD) for both TDG and TDG plus TDGO (TDG + TDGO) were 0.1 ng
      mL(-1), and the limits of quantitation (LOQ) for both were 0.3 ng mL(-1). The
      method was used in a rabbit cutaneous SM exposure model. Domestic rabbits were
      exposed to neat liquid SM at three dosage levels (0.02, 0.05, and 0.15 LD50), and
      the urinary excretion of four species of hydrolysis metabolites, namely free TDG,
      free plus conjugated TDG (total TDG), free TDG + TDGO, and free plus conjugated
      TDG + TDGO (total TDG + TDGO), was evaluated to investigate the metabolic
      processes. The total urinary excretion profiles of the metabolites, including the
      peak time, time window, and dose-response and time-response relationships, were
      clarified. The results revealed that the concentrations of TDG and TDG + TDGO in
      the urine increased quickly and then decreased rapidly in the first two days
      after SM exposure. The cumulative amount of total TDG + TDGO excreted in urine
      during the first five days accounted for 0.5-1% of the applied dose of SM. It is
      also concluded that TDG and TDGO in urine existed mainly in free form, the levels
      of glucuronide and of sulfate conjugates of TDG or TDGO were very low, and most
      hydrolysis metabolites were present in the oxidized form (TDGO). The study
      indicates that the abnormal increase of TDG and TDGO excretion levels can be used
      as a diagnostic indicator and establishes a reference time-window for
      retrospective analysis and sampling after SM exposure.

PMID- 24924211
TI  - The impact of immobilized metal affinity chromatography (IMAC) resins on DNA
      aptamer selection.
AB  - DNA aptamers are single-stranded oligonucleotides which can form various
      secondary and tertiary structures. They can recognize a broad range of targets
      ranging from small molecules, such as ions, vitamins, antibiotics, to high
      molecular weight structures, including enzymes and antibodies. DNA aptamers are
      extensively studied as a potential source of new pharmaceutical drugs due to
      their inexpensive synthesis, low immunogenicity, and high specificity. The
      commonly used aptamer selection procedure is systematic evolution of ligands by
      exponential enrichment (SELEX) where the target molecule is immobilized on an
      appropriate chromatography resin. For peptide/protein targets, immobilized metal
      affinity chromatography (IMAC) resins are frequently used. There is a broad range
      of commercially available resins which can be used for IMAC. They are
      characterized by different metal ions, linker types, and bead materials. In this
      study, we tested the impact of different IMAC resins on the DNA aptamer selection
      process during eight SELEX cycles. A histidine-tagged 29 amino acid peptide
      corresponding to the interdomain connecting loop of human proliferating cell
      nuclear antigen was used as a selection target. Different resin materials
      containing the same metal ion (Co(2+)) were tested. Simultaneously, agarose
      resins containing identical linkers, but different metal ions (Co(2+), Cu(2+),
      Ni(2+), and Zn(2+)) were analyzed. The results of this study clearly demonstrated
      the impact of the metal ion and resin material on the DNA aptamer selection
      progress. The presented data indicate that for successful IMAC resin-based SELEX,
      the determination of the optimal resin might be crucial. 

PMID- 24924212
TI  - Targeting lysosomal membrane permeabilization to induce and image apoptosis in
      cancer cells by multifunctional Au-ZnO hybrid nanoparticles.
AB  - We have developed multifunctional Au-ZnO hybrid nanoparticles (NPs) for targeted
      induction lysosomal membrane permeabilization (LMP)-dependent apoptosis in cancer
      cells and real-time imaging. 

PMID- 24924213
TI  - Non-contrast-enhanced MR portography with balanced steady-state free-precession
      sequence and time-spatial labeling inversion pulses: comparison of imaging with
      flow-in and flow-out methods.
AB  - PURPOSE: To compare and evaluate images of non-contrast-enhanced MR portography
      acquired with two different methods, the flow-in and flow-out methods. MATERIALS
      AND METHODS: Twenty-five healthy volunteers were examined using respiratory
      triggered three-dimensional balanced steady-state free-precession (SSFP) with two
      selective inversion recovery pulses (flow-in method) and one tagging pulse and
      one nonselective inversion recovery pulse (flow-out method). For quantitative
      analysis, vessel-to-liver contrast (Cv-l) ratios of the main portal vein (MPV),
      right portal vein (RPV), and left portal vein (LPV) were measured. The quality of
      portal vein visualization was scored using a four-point scale. RESULTS: The Cv-ls
      of the MPV, RPV, and LPV were all significantly higher with the flow-out than
      flow-in method (MPV = 0.834 +/- 0.06 versus 0.711 +/- 0.10; RPV = 0.861 +/- 0.04
      versus 0.729 +/- 0.11; LPV = 0.786 +/- 0.08 versus 0.545 +/- 0.22; P < 0.0001).
      In all analyses of vessel visibility, non-contrast-enhanced MR portography with
      the flow-out method showed higher scores than with the flow-in method. With the
      flow-out method, visual scores of the MPV, RPV, portal vein branches of segments
      4 (P4), and 8 (P8) were significantly better than with the flow-in method (MPV =
      3.4 +/- 0.7 versus 2.6 +/- 0.9; RPV = 4.0 +/- 0.0 versus 3.5 +/- 0.9; P4 = 2.8 +/
      1.3 versus 1.6 +/- 1.0; P8 = 4.0 +/- 0.0 versus 2.9 +/- 1.1; P < 0.05).
      CONCLUSION: Non-contrast-enhanced MR portography with the flow-out method
      improves the visualization of the intrahepatic portal vein in comparison with the
      flow-in method. J. Magn. Reson. Imaging 2014;40:583-587. (c) 2013 Wiley
      Periodicals, Inc.

PMID- 24924214
TI  - Zinc, magnesium, and calcium ion supplementation confers tolerance to acetic acid
      stress in industrial Saccharomyces cerevisiae utilizing xylose.
AB  - Lignocellulosic biomass is a potential substrate for ethanol production. However,
      pretreatment of lignocellulosic materials produces inhibitory compounds such as
      acetic acid, which negatively affect ethanol production by Saccharomyces
      cerevisiae. Supplementation of the medium with three metal ions (Zn(2+) , Mg(2+)
      , and Ca(2+) ) increased the tolerance of S. cerevisiae toward acetic acid
      compared to the absence of the ions. Ethanol production from xylose was most
      improved (by 34%) when the medium was supplemented with 2 mM Ca(2+) , followed by
      supplementation with 3.5 mM Mg(2+) (29% improvement), and 180 MUM Zn(2+) (26%
      improvement). Higher ethanol production was linked to high cell viability in the
      presence of metal ions. Comparative transcriptomics between the supplemented
      cultures and the control suggested that improved cell viability resulted from the
      induction of genes controlling the cell wall and membrane. Only one gene, FIT2,
      was found to be up-regulated in common between the three metal ions. Also up
      regulation of HXT1 and TKL1 might enhance xylose consumption in the presence of
      acetic acid. Thus, the addition of ionic nutrients is a simple and cost-effective
      method to improve the acetic acid tolerance of S. cerevisiae. 

PMID- 24924215
TI  - Partners' clinic: an innovative gender strengths-based intervention for breast
      cancer patients and their partners immediately prior to initiating care with
      their treating physician.

PMID- 24924216
TI  - Myocardial fibrosis evaluated by Look-Locker and late gadolinium enhancement
      magnetic resonance imaging in apical hypertrophic cardiomyopathy: association
      with ventricular tachyarrhythmia and risk factors.
AB  - PURPOSE: To evaluate the distribution and extent of myocardial fibrosis
      identified by either contrast-enhanced Look-Locker or late gadolinium enhancement
      magnetic resonance imaging (LGE MRI) and their relationships between ventricular
      tachyarrhythmia or risk factors in apical hypertrophic cardiomyopathy (APH).
      MATERIALS AND METHODS: Twenty-five APH patients were examined using a 3.0 T or
      1.5 T instrument. We used MRI to evaluate myocardial T1 values and scar. We
      compared the myocardial fibrosis assessed by contrast-enhanced Look-Locker or LGE
      MRI with ventricular tachyarrhythmia or risk factors for hypertrophic
      cardiomyopathy. RESULTS: Myocardial scar was present in 17 of the 25 patients
      with APH. Myocardial scar was distributed predominantly in the apical myocardium
      (P < 0.01), whereas myocardial T1 values did not differ between the apical,
      midventricular, and basal septum. The extent of myocardial scar according to 16
      segment model and ejection fraction were related to ventricular tachyarrhythmia
      or risk factors in APH (P < 0.05 for both). The myocardial T1 value was not
      associated with the tachyarrhythmia or risk factors. CONCLUSION: In APH, the
      extent of myocardial scar on LGE MRI is associated with ventricular
      tachyarrhythmia and risk factors. Quantification of the myocardial T1 value is
      not necessary for its risk stratification.

PMID- 24924217
TI  - Evaluation of oscillometric and Doppler ultrasonic devices for blood pressure
      measurements in anesthetized and conscious dogs.
AB  - Two non-invasive blood pressure (NIBP) devices (oscillometry and Doppler) were
      compared to invasive blood pressure using a Bland-Altman analysis, in
      anesthetized and conscious dogs. When considering the systolic arterial pressure
      only during general anesthesia, both NIBP devices slightly underestimated the
      systolic arterial blood pressure however the precision and the limits of
      agreement for the Doppler were of a greater magnitude. This indicates a worse
      clinical performance by the Doppler. The performance of both NIBP devices
      deteriorated as measured in conscious animals. In general, for the oscillometric
      device, determination of invasive diastolic and mean arterial pressures was
      better than the invasive systolic arterial pressure. Overall, the oscillometric
      device satisfied more of the criteria set by the American College of Veterinary
      Internal Medicine consensus statement. Based upon these results, the
      oscillometric device is more reliable than the Doppler in the determination of
      blood pressure in healthy medium to large breed dogs. 

PMID- 24924218
TI  - Training shelter volunteers to teach dog compliance.
AB  - This study examined the degree to which training procedures influenced the
      integrity of behaviorally based dog training implemented by volunteers of an
      animal shelter. Volunteers were taught to implement discrete-trial obedience
      training to teach 2 skills (sit and wait) to dogs. Procedural integrity during
      the baseline and written instructions conditions was low across all participants.
      Although performance increased with use of a video model, integrity did not reach
      criterion levels until performance feedback and modeling were provided. Moreover,
      the integrity of the discrete-trial training procedure was significantly and
      positively correlated with dog compliance to instructions for all dyads. Correct
      implementation and compliance were observed when participants were paired with a
      novel dog and trainer, respectively, although generalization of procedural
      integrity from the discrete-trial sit procedure to the discrete-trial wait
      procedure was not observed. Shelter consumers rated the behavior change in dogs
      and trainers as socially significant. Implications of these findings and future
      directions for research are discussed. 

PMID- 24924219
TI  - Processing of gelatin-based cryogels with improved thermomechanical resistance,
      pore size gradient, and high potential for sustainable protein drug release.
AB  - Porous gelatin (GEL) cryogels were processed by spatiotemporal and temperature
      controlled gelation and freezing-lyophilizaton process, followed by zero-length
      crosslinking, using different molarities of reagents (EDC and NHS) and reaction
      media (100% PBS or 20/80% PBS/EtOH mixture) for variable time extensions (1-24
      h). In this way, tuneable cryogels with gradient microporosity (from 100 um to
      1000 um) were formed, being mainly influenced by crosslinkers' concentration and
      EtOH addition. Later affect the pore morphology (from round to ellipsoid),
      consequently modulating the steady-state physiological swelling profile toward
      twice lower values (~ 600%) comparing to stepwise swelling of in 100% PBS media
      crosslinked cryogels. While the presence of EtOH decelerate the crosslinking
      kinetic by retaining cryogels' microstructure formed during freezing, the 100%
      PBS and higher EDC molarity resulted in approximately 40% crosslinking degree,
      being expressed as a thermal resistance of cryogels up to approximately 73
      degrees C. Finally, the tuneable enzymatic resistance allow time-dependent poly-L
      Lysine (pL) release profile in up to month period. The processed GEL cryogels
      have potential in broad range biomedical applications, especially as sustainable,
      protein-based drug delivery systems.

PMID- 24924220
TI  - On the mechanism of intramolecular nitrogen-atom hopping in the carbon chain of
      C6N radical: a plausible 3c-4e crossover pi long-bond.
AB  - Linear isomers of C6N radical differ in the position of the nitrogen atom in the
      carbon chain of C6N. Reaction routes, involving intramolecular nitrogen atom
      insertion at varying position in the carbon chain of C6N, are analyzed for the
      isomerisation between linear isomers of C6N. Through an automated and systematic
      search performed with global reaction route mapping of the potential energy
      surface, thermal isomerisation pathways for C6N radical are proposed based on the
      computations carried out at CASSCF/aug-cc-pVTZ, and CCSD(T)/6
      311++G(d,p)//B3LYP/6-311++G(d,p) levels of the theory. Notably, a high lying
      linear isomer, centrosymmetric with respect to the nitrogen atom, is observed to
      be stabilized by a unique crossover three center-four electron pi long bond
      between the carbon atoms that are spatially separated by a nitrogen atom in a
      natural bond orbital. This long bond is concluded to be responsible for the
      predicted thermal isomerisation to be more feasible than the dissociation during
      the isomerisation pathway of a linear isomer of C6N.

PMID- 24924221
TI  - BOLD signal change and contrast reversing frequency: an event-related fMRI study
      in human primary visual cortex.
AB  - It is believed that human primary visual cortex (V1) increases activity with
      increasing temporal frequency of a visual stimulus. Two kinds of visual stimulus
      were used in the previous studies, one is patterned-flash stimulus with a fixed
      onset period and an increasing average luminance with the increase of temporal
      frequency, the other is contrast reversing flickering checkerboard or grating
      with a constant average luminance across different temporal frequencies. That
      hemodynamic responses change as a function of reversal frequency of contrast
      reversing checkerboard is at odds with neurophysiological studies in animals and
      neuroimaging studies in humans. In the present study, we addressed the
      relationship between reversal frequency of contrast reversing checkerboard and
      hemodynamic response in human V1 using an event-related experimental paradigm and
      found that the transient characteristics of blood oxygenation level dependent
      response in human V1 depended very little on the reversal frequency of a contrast
      reversing checkerboard. 

PMID- 24924223
TI  - Investigating the relationship between prenatal growth and postnatal outcomes: a
      systematic review of the literature.
AB  - Theories regarding the relationship between pre- and postnatal growth and
      programming of health have been based on characteristics at birth, with little or
      no reference to the patterns of growth occurring in utero. Review of the
      literature to identify studies using ultrasonographically obtained fetal
      dimensions to track prenatal growth and relate these patterns of growth to
      postnatal anthropometry and cardiovascular and metabolic risk factors. Review of
      Medline, Scopus and Proquest for studies reporting on ultrasonographically
      derived estimates of fetal growth and their association with postnatal
      anthropometry, body composition or cardiovascular and metabolic risk factors.
      Quality of papers were assessed using the method developed by Downs and Black.
      Twenty-nine studies met the inclusion criteria, with a mean score of high
      quality. Twenty of the studies had follow-up in infancy, five in childhood, three
      in adolescence and one in adulthood. The associations observed suggest that
      centile tracking may occur early in pregnancy though whether this is as early as
      the first trimester is uncertain. The second trimester may be a critical period
      for the programming of blood pressure and abdominal circumference may be the most
      sensitive fetal dimension to indicate any programming. 

PMID- 24924224
TI  - The role of folic acid in fetal programming of birth phenotypes and early human
      development: a biopsychosocial perspective.
AB  - Preterm birth, low birthweight, intrauterine growth retardation and small for
      gestational age are birth phenotypes that significantly contribute to life-long
      morbidity and mortality. This review examines the epidemiologic and biologic
      evidence of folic acid (FA) as a potential population-based intervention to
      curtail some adverse birth phenotypic expressions, and by extension, their later
      physical and neurodevelopmental consequences. We outlined a feto-placental
      adaptation categorization taking into account how prenatal insults may be encoded
      in fetal development, the adaptive success of the feto-placental response, and
      subsequent expression in the health of the fetus. Although there are plausible
      biological pathways that can be implicated, we found that the epidemiological
      evidence on the role of perinatal FA nutriture and fetal programming of adverse
      birth phenotypes is still inconclusive. Because biologic and epidemiological
      considerations alone do not suffice in deciphering the utility of FA in averting
      adverse birth phenotypes, we proposed a biopsychosocial model that takes into
      account multi-layered psychosocial contexts for improving subsequent research
      studies in this area. 

PMID- 24924222
TI  - Deletion of astroglial CXCL10 delays clinical onset but does not affect
      progressive axon loss in a murine autoimmune multiple sclerosis model.
AB  - Multiple sclerosis (MS) is characterized by central nervous system (CNS)
      inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine
      for CXCR3+ T cells, is known to regulate T cell differentiation and migration in
      the periphery, but effects of CXCL10 produced endogenously in the CNS on immune
      cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with
      mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial
      CXCL10 synthesis. These mice, and littermate controls, were immunized with myelin
      oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) to induce experimental
      autoimmune encephalomyelitis (EAE). In comparison to the control mice, spinal
      cord CXCL10 mRNA and protein were sharply diminished in the mGFAPcre/CXCL10fl/fl
      EAE mice, confirming that astroglia are chiefly responsible for EAE-induced CNS
      CXCL10 synthesis. Astroglial CXCL10 deletion did not significantly alter the
      overall composition of CD4+ lymphocytes and CD11b+ cells in the acutely inflamed
      CNS, but did diminish accumulation of CD4+ lymphocytes in the spinal cord
      perivascular spaces. Furthermore, IBA1+ microglia/macrophage accumulation within
      the lesions was not affected by CXCL10 deletion. Clinical deficits were milder
      and acute demyelination was substantially reduced in the astroglial CXCL10
      deleted EAE mice, but long-term axon loss was equally severe in the two groups.
      We concluded that astroglial CXCL10 enhances spinal cord perivascular CD4+
      lymphocyte accumulation and acute spinal cord demyelination in MOG peptide EAE,
      but does not play an important role in progressive axon loss in this MS model.

PMID- 24924225
TI  - Platelet-activating factor synthesis and receptor-mediated signaling are
      downregulated in ovine newborn lungs: relevance in postnatal pulmonary adaptation
      and persistent pulmonary hypertension of the newborn.
AB  - Platelet-activating factor (PAF) is a phospholipid with a wide range of
      biological activities. We studied PAF metabolism and PAF receptor (PAFR)
      signaling in perinatal ovine lungs to understand PAF's role in transition of the
      perinatal pulmonary hemodynamics and pathophysiology of persistent pulmonary
      hypertension of the newborn. We hypothesized that downregulation of PAF synthesis
      with upregulation of PAF catabolism by acetylhydrolase (PAF-Ah) in the newborn
      lung is needed for fetus-to-newborn pulmonary adaptation. Studies were conducted
      on fetal and newborn lamb pulmonary arteries (PA), veins (PV) and smooth muscle
      cells (SMC). PAF metabolism, PAFR binding and cell proliferation were studied by
      cell culture; gene expression was studied by qPCR. Fetal lungs synthesized 60%
      more PAF than newborn lungs. Compared with the fetal PVs and SMCs, PAF-Ah
      activity in newborn was 40-60% greater. PAF-Ah mRNA expression in newborn vessels
      was different from the expression by fetal PA. PAF-Ah gene clone activity
      confirmed deletion of hypoxia-sensitive site. PAFR mRNA expression by the PVs and
      SMC-PV of the fetus and newborn was greater than by corresponding PAs and SMC-PA.
      Q-PCR study of PAFR expression by the SMC-PV of both groups was greater than SMC
      PA. Fetal SMCs bound more PAF than the newborn SMCs. PAFR antagonist, CV-3988,
      inhibited PAFR binding and DNA synthesis by the fetal SMCs, but augmented binding
      and DNA synthesis by newborn cells. We show different PAF-PAFR mediated effects
      in perinatal lungs, suggesting both transcriptional and translational regulation
      of PAF-Ah and PAFR expression in the perinatal lamb lungs. These indicate that
      the downregulation of PAF-mediated effects postnatally protects against
      persistent pulmonary hypertension of the newborn. 

PMID- 24924226
TI  - Increased collagen deposition in the heart of chronically hypoxic ovine fetuses.
AB  - This study determined the effect of chronic intrauterine hypoxia on collagen
      deposition in the fetal sheep heart. Moderate or severe hypoxia was induced by
      placental embolization in chronically catheterized fetal sheep for 15 days
      starting at gestational day 116 +/- 2 (term ~147 days). The fetal right and left
      ventricle were evaluated for collagen content using a Sirius red dye and for
      changes in signaling components of pathways involved in collagen synthesis and
      remodeling using quantitative polymerase chain reaction and Western blot. In
      severely hypoxic fetuses (n = 6), there was a two-fold increase (P < 0.05) in the
      percentage staining for collagen in the right ventricle, compared with control (n
      = 6), whereas collagen content was not altered in the moderate group (n = 4).
      Procollagen I and III mRNA levels were increased in the right ventricle, two-fold
      (P < 0.05) and three-fold (P < 0.05), respectively, in the severe group relative
      to control. These changes were paralleled by a two-fold increase (P < 0.05) in
      mRNA levels of the pro-fibrotic cytokine, transforming growth factor beta (TGF
      beta1), in the right ventricle. In the right ventricle, the mRNA levels of matrix
      metalloproteinase 2 (MMP-2) and its activator, membrane-type MMP (MTI-MMP) were
      increased five-fold (P = 0.06) and three-fold (P < 0.05), respectively, relative
      to control. Protein levels of TGF-beta were increased in the left ventricle (P <
      0.05). Thus, up-regulated collagen synthesis leading to increased collagen
      content occurs in the chronically hypoxic fetal heart and may contribute to the
      right ventricular diastolic and systolic dysfunction reported in human
      intrauterine growth restriction fetuses. 

PMID- 24924227
TI  - Epigenetic changes in hypothalamic appetite regulatory genes may underlie the
      developmental programming for obesity in rat neonates subjected to a high
      carbohydrate dietary modification.
AB  - Earlier, we showed that rearing of newborn rats on a high-carbohydrate (HC) milk
      formula resulted in the onset of hyperinsulinemia, its persistence in the post
      weaning period and adult-onset obesity. DNA methylation of CpG dinucleotides in
      the proximal promoter region and modifications in the N-terminal tail of histone
      3 associated with the neuropeptide Y (Npy) and pro-opiomelanocortin (Pomc) genes
      were investigated to decipher the molecular mechanisms supporting the development
      of obesity in HC females. Although there were no differences in the methylation
      status of CpG dinucleotides in the proximal promoter region of the Pomc gene,
      altered methylation of specific CpG dinucleotides proximal to the transcription
      start site was observed for the Npy gene in the hypothalami of 16- and 100-day
      old HC rats compared with their methylation status in mother-fed (MF) rats.
      Investigation of histone tail modifications on hypothalamic chromatin extracts
      from 16-day-old rats indicated decreased acetylation of lysine 9 in histone 3
      (H3K9) for the Pomc gene and increased acetylation for the same residue for the
      Npy gene, without changes in histone methylation (H3K9) in both genes in HC rats.
      These findings are consistent with the changes in the levels of Npy and Pomc
      mRNAs in the hypothalami of HC rats compared with MF animals. Our results suggest
      that epigenetic modifications could contribute to the altered gene expression of
      the Npy and Pomc genes in the hypothalami of HC rats and could be a mechanism
      leading to hyperphagia and the development of obesity in adult female HC rats. 

PMID- 24924228
TI  - Circulating levels of the cytokines IL10, IFNgamma and resistin in an obese mouse
      model of developmental programming.
AB  - An infant's early developmental environment plays a pivotal role in the
      programming of its physiological phenotype. The identification of the factors in
      the maternal environment that mediate the effects of maternal obesity and diet is
      essential to the development of clinical intervention strategies. Maternal
      hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, hyperleptinaemia and
      altered inflammatory cytokines concentrations are potentially important
      predictive factors of her future offspring's susceptibility to metabolic disease.
      Using a diet-induced obese mouse model, we have investigated which of these
      maternal factors could induce adverse metabolic programming in the offspring.
      Female C57Bl/6 mice were fed either laboratory chow (10% fat) or high fat diet
      (42% fat) for 10 weeks before mating and throughout gestation. At day 18 of
      pregnancy, maternal body weight, body composition and glucose tolerance were
      measured, as well as plasma insulin, adiponectin, RBP4, leptin, resistin and the
      inflammatory cytokines (IL6, IL10, IL12, IL1beta, IFNgamma, KC, TNF-alpha). At
      day 18 of pregnancy, high fat-fed dams were significantly heavier than the chow
      dams and had increased fat mass. High fat-fed dams had higher 5 h fasting blood
      glucose than chow dams and elevated plasma insulin. Although the obese dams had
      both reduced plasma adiponectin and resistin levels compared with lean dams,
      their plasma IL6, IL10 and IFNgamma levels were all increased. High fat feeding
      in pregnancy leads to altered plasma concentrations of both adipokines and
      adipocytokines in the dam that may directly pass to the fetus and affect their
      development. 

PMID- 24924229
TI  - Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm
      small for gestational age infants.
AB  - Low birth weight was associated with cardiometabolic diseases in adult age.
      Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also
      associates with cardiometabolic risks in adults. Therefore, we elucidated the
      association between IGF-1 level and serum lipids in cord blood of preterm
      infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14
      female) born at <37-week gestational age, including 10 small for gestational age
      (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in
      cord blood, and high-density lipoprotein cholesterol (HDLC), low-density
      lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride
      (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1
      +/- 5.3 ng/ml), total cholesterol (TC) (55.0 +/- 14.8), LDLC (21.6 +/- 8.3) and
      HDLC (26.3 +/- 11.3) levels, and higher VLDLTG levels (19.0 +/- 12.7 mg/dl) than
      in appropriate for gestational age (AGA) infants (53.6 +/- 25.6, 83.4 +/- 18.9,
      36.6 +/- 11.1, 38.5 +/- 11.6, 8.1 +/- 7.0, respectively). In simple regression
      analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P <
      0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels
      (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and
      log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated
      that IGF-1 was an independent predictor of TC, HDLC and TG levels after the
      gestational age and birth weight were taken into account. In preterm SGA infants,
      cord blood lipids profile altered with the concomitant decrease in IGF-1 level. 

PMID- 24924230
TI  - Intrauterine environment and cognitive development in young twins.
AB  - Intrauterine factors important for cognitive development, such as birth weight,
      chorionicity and umbilical cord characteristics were investigated. A total of 663
      twin pairs completed the Wechsler Intelligence Scale for Children-Revised and
      scores were available for Performance, Verbal and Total Intelligence Quotient
      (IQ). The intrauterine factors examined were birth weight, placental weight and
      morphology, cord knots, cord length and cord insertion. IQ scores for the varying
      levels of the intrauterine markers adjusting for gender and gestational age were
      calculated. The heritability of IQ and the association between IQ and
      intrauterine environment were examined. Twins with lower birth weight and cord
      knots had lower IQ scores. The aetiology of IQ is largely distinct from that of
      birth weight and cord knots, and non-shared environment may influence the
      observed relationships. 

PMID- 24924231
TI  - Characterization of the role of microRNA-517a expression in low birth weight
      infants.
AB  - The purpose of this study was to analyze the expression of the placenta-specific
      microRNA miR-517a in maternal serum and in placental tissue from low birth weight
      newborns and try to detect the effects of miR-517a expression on invasion
      potential of trophoblasts. Placental tissue and maternal serum were collected
      from both low birth weight newborns (n = 10) and normal birth weight newborns (n
      = 20). Expression of miR-517a was assessed in placenta and serum samples by real
      time qRT-PCR. In addition, human trophoblast HTR8/SVneo cells were transfected
      with a miR-517a 2'-O-methyl oligonucleotide or a negative control RNA, and
      invasion was measured using transwell migration assays. Expression of miR-517a
      was significantly increased in placentas from low birth weight newborns (61.79 +/
      23.06) in comparison with those of normal birth weight newborns (5.01 +/- 1.97;
      P < 0.05). The expression of miR-517a was also increased in maternal serum
      isolated from the low birth weight newborn (25.78 +/- 8.69) compared with the
      normal birth weight newborn (3.21 +/- 1.07; P < 0.05). Overexpression of miR-517a
      significantly inhibited invasion of HTR8/SVneo cells (P < 0.05). These data
      indicate that miR-517a overexpression could potentially lead to low birth weight,
      likely through the inhibition of trophoblast invasion. 

PMID- 24924233
TI  - Establishing the bidirectional relationship between depression and subclinical
      arteriosclerosis--rationale, design, and characteristics of the BiDirect Study.
AB  - BACKGROUND: Depression and cardiovascular diseases due to arteriosclerosis are
      both frequent and impairing conditions. Depression and (subclinical)
      arteriosclerosis appear to be related in a bidirectional way, and it is plausible
      to assume a partly joint causal relationship. However, the biological mechanisms
      and the behavioral pathways that lead from depression to arteriosclerosis and
      vice versa remain to be exactly determined. METHODS/DESIGN: This study protocol
      describes the rationale and design of the prospective BiDirect Study that aims at
      investigating the mutual relationship between depression and (subclinical)
      arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of
      individuals ((i) patients with acute depression (N = 999), (ii) patients after an
      acute cardiac event (N = 347), and (iii) reference subjects from the general
      population (N = 912)). Over the course of 12 years, four personal examinations
      are planned to be conducted. The core examination program, which will remain
      identical across follow-ups, comprises a personal interview (e.g. medical
      diagnoses, health care utilization, lifestyle and risk behavior), a battery of
      self-administered questionnaires (e.g. depressive symptoms, readiness to change
      health behavior, perceived health-related quality of life), sensory (e.g.
      olfaction, pain) and neuropsychological (e.g. memory, executive functions,
      emotional processing, manual dexterity) assessments, anthropometry, body
      impedance measurement, a clinical work-up regarding the vascular status (e.g.
      electrocardiogram, blood pressure, intima media thickness), the taking of blood
      samples (serum and plasma, DNA), and structural and functional resonance imaging
      of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces
      processing). The present report includes BiDirect-Baseline, the first data
      collection wave. DISCUSSION: Due to its prospective character, the integration of
      three distinct cohorts, the long follow-up time window, the diligent diagnosis of
      depression taking depression subtypes into account, the consideration of relevant
      comorbidities and risk factors, the assessment of indicators of (subclinical)
      arteriosclerosis in different vascular territories, and the structural and
      functional brain imaging that is performed for a large number of participants,
      the BiDirect Study represents an innovative approach that combines population
      based cohorts with sophisticated clinical work-up methods and that holds the
      potential to overcome many of the drawbacks characterizing earlier
      investigations.

PMID- 24924232
TI  - Exploring effects of a natural combination medicine on exercise-induced
      inflammatory immune response: A double-blind RCT.
AB  - Traumeel (Tr14) is a natural, combination drug, which has been shown to modulate
      inflammation at the cytokine level. This study aimed to investigate potential
      effects of Tr14 on the exercise-induced immune response. In a double-blind,
      randomized, controlled trial, healthy, untrained male subjects received either
      Tr14 (n = 40) or placebo (n = 40) for 24 h after a strenuous experimental
      exercise trial on a bicycle (60 min at 80%VO2 max). A range of antigen-stimulated
      cytokines (in vitro), white blood cell count, lymphocyte activation and apoptosis
      markers, and indicators of muscle damage were assessed up to 24 h following
      exercise. The area under the curve with respect to the increase (AUCI ) was
      compared between both groups. The Tr14 group showed a reduced exercise-induced
      leukocytosis and neutrocytosis (P < 0.01 for both), a higher AUCI score of
      antigen-stimulated IL-1beta and IL-1alpha (absolute and per monocyte, all P <
      0.05), a lower AUCI score of antigen-stimulated GM-CSF (P < 0.05) and by trend a
      lower AUCI score of antigen-stimulated IL-2 and IL-4 as well as a higher AUCI
      score of antigen-stimulated IL-6 (all P < 0.1). Tr14 might promote differentiated
      effects on the exercise-induced immune response by (a) decreasing the
      inflammatory response of the innate immune system; and (b) augmenting the pro
      inflammatory cytokine response.

PMID- 24924235
TI  - Influence of kinin peptides on monocyte-endothelial cell adhesion.
AB  - Adhesion of leukocytes to vascular endothelium in response to proinflammatory
      mediators is an important component of the overall inflammatory reaction. In the
      current work, we used a retinoic acid-differentiated human promonocytic cell
      line, U937 and a human microvascular endothelial cell line, HMEC-1 to analyze the
      effect of the potent pro-inflammatory bradykinin-related peptides (kinins) on
      cell adhesion. Bradykinin (BK) and kinin metabolites without the C-terminal
      arginine residue enhanced adhesion of the monocyte-like cells to fibronectin and
      to the HMEC-1 cells. Expression of adhesion proteins on the surface of both cell
      types was altered by the kinin peptides. In the monocyte-like cells, expression
      of CD11b, a subunit of Mac-1 integrin, was significantly increased whilst in the
      endothelial cells, a strong increase in the production of intercellular adhesion
      molecule 1 (ICAM-1) was observed. The positive bradykinin-induced effect on the
      cell-cell interaction was reversed by a carboxypeptidase inhibitor (MGTA), hence
      we suspected a significant role of the des-Arg kinin metabolites, which acted
      through the kinin receptor type 1. Indeed, the expression of this receptor was up
      regulated not only by agonists but also by interferon-gamma and bradykinin. Kinin
      peptides also regulated signal transducer and activator of transcription proteins
      (STATs) activated by cytokines. Taken together, the above observations support
      our hypothesis that kinins stimulate monocyte adhesion to the vessel wall,
      especially during pathological states of the circulatory system accompanied by
      proinflammatory cytokine release.

PMID- 24924236
TI  - JPS Global Workshop Kyoto 2012: introduction.

PMID- 24924234
TI  - Gibberellin deficiency pleiotropically induces culm bending in sorghum: an
      insight into sorghum semi-dwarf breeding.
AB  - Regulation of symmetrical cell growth in the culm is important for proper culm
      development. So far, the involvement of gibberellin (GA) in this process has not
      yet been demonstrated in sorghum. Here, we show that GA deficiency resulting from
      any loss-of-function mutation in four genes (SbCPS1, SbKS1, SbKO1, SbKAO1)
      involved in the early steps of GA biosynthesis, not only results in severe
      dwarfism but also in abnormal culm bending. Histological analysis of the bent
      culm revealed that the intrinsic bending was due to an uneven cell proliferation
      between the lower and upper sides of culm internodes. GA treatment alleviated the
      bending and dwarfism in mutants, whereas the GA biosynthesis inhibitor,
      uniconazole, induced such phenotypes in wild-type plants--both in a concentration
      dependent manner, indicating an important role of GA in controlling erectness of
      the sorghum culm. Finally, we propose that because of the tight relationship
      between GA deficiency-induced dwarfism and culm bending in sorghum, GA-related
      mutations have unlikely been selected in the history of sorghum breeding, as
      could be inferred from previous QTL and association studies on sorghum plant
      height that did not pinpoint GA-related genes.

PMID- 24924237
TI  - The role of contextual cues in operant responding in rats.
AB  - Following lever-press training on a variable-interval 60-second schedule of food
      presentation, groups of rats either remained in their home cages or were exposed
      to the operant chamber, from which lever and food had been removed, for five
      sessions. The lever was replaced in the chamber and rats from Group 1 (exposure
      to chamber) and Group 3 (home cage) were returned to the variable-interval
      schedule. Although response rates in test sessions were somewhat lower than at
      the end of training, there was no statistically significant difference in rates
      for either group. Rats in Group 2 (exposure to chamber) and Group 4 (home cage)
      received two test sessions of extinction. During the first session, Group 2 rates
      of lever pressing were significantly higher than Group 4 rates. These findings do
      not support the view that associations between contextual cues and the reinforcer
      serve to energize instrumental behavior (Pearce & Hall, 1979), and provide only
      minimal support for the view that contextual cues control responses that compete
      with the operant (Mills, 1980). 

PMID- 24924238
TI  - Mirror-image reactions in a tool-using, adult male Macaca tonkeana.
AB  - This study examined reactions to mirror-image stimulation in a wild- reared adult
      male monkey (Macaca tonkeana) which had spontaneously developed a form of tool
      use, namely the use of plant stems to reach mucus inside the nose. Initial
      intense social responsiveness to the mirror was followed by habituation, although
      some social responding persisted. Mirror- induced social facilitation of drinking
      was demonstrated, the first record of such an effect in a nonhuman primate.
      Rather than enhancing the subject's tool-using activity, the presence of the
      mirror disrupted tool-use. Finally, an objective test for the presence of self
      recognition failed to obtain any evidence of self-recognition in the subject,
      lending support to the view that the capacity for self-recognition may be lacking
      in monkeys. 

PMID- 24924239
TI  - Relative importance of distance senses in hamster predatory behavior.
AB  - This study examined the relative importance vision, audition and olfaction played
      in the localization of prey in the golden hamster (Mesocricetus auratus ). These
      three senses were blocked singly or in various combinations so that a hamster was
      tested under eight different situations with a tethered cricket and four
      situations with a dead cricket. Vision, audition and olfaction all contributed to
      localization of a tethered cricket with vision playing the dominant role. In
      localization of a stationary cricket, a hamster used both vision and olfaction to
      find a prey. Comparison of these data with that from a similar study with the
      grasshopper mouse showed that the relative roles these distance senses played in
      predation of these two rodents was substantially different. 

PMID- 24924240
TI  - Properties of behavior under different random ratio and random interval
      schedules: A parametric study.
AB  - Four pigeons were trained to peck a key under different values of a temporally
      defined independent variable (T) and different probabilities of reinforcement
      (p). Parameter T is a fixed repeating time cycle and p the probability of
      reinforcement for the first response of each cycle T. Two dependent variables
      were used: mean response rate and mean postreinforcement pause. For all values of
      p a critical value for the independent variable T was found (T=1 sec) in which
      marked changes took place in response rate and postreinforcement pauses. Behavior
      typical of random ratio schedules was obtained at T 1 sec and behavior typical of
      random interval schedules at T 1 sec. 

PMID- 24924241
TI  - Constraining response output on conjunctive fixed-ratio 1 fixed-time
      reinforcement schedules: Effects on the postreinforcement pause.
AB  - Two experiments used response-restriction procedures in order to test the
      independence of the factors determining response rate and the factors determining
      the size of the postreinforcement pause on interval schedules. Responding was
      restricted by response-produced blackout or by retracting the lever. In
      Experiment 1 with a Conjunctive FR 1 FT schedule, the blackout procedure reduced
      the postreinforcement pause more than the lever-retraction procedure did, and
      both procedures produced shorter pauses than did the schedule without response
      restriction. In Experiment 2 the interreinforcement interval was also
      manipulated, and the size of the pause was an increasing function of the
      interreinforcement interval, but the rate of increase was lower than that
      produced by fixed interval schedules of comparable interval durations. The
      assumption of functional independence of the postreinforcement pause and terminal
      rate in fixed interval schedules is questioned since data suggest that pause
      reductions resulted from constraining variation in response number compared to
      equivalent periodic schedules in which response number was allowed to vary. 

PMID- 24924242
TI  - Telencephalic removal and tonic immobility in the domestic hen (Gallus Domesticus
      ).
AB  - The number of inductions and the duration of tonic immobility (TI) was measured
      in Brown Leghorn hens which were either sham-operated or had total removal of the
      telencephalon. The overall duration of TI was shorter in sham-operated birds than
      in decerebrates. The duration of TI decreased significantly in both groups when
      they were given one trial daily for 7 consecutive days but this was not seen when
      the birds received 5 trials in rapid succession. The number of inductions
      necessary to produce TI in decerebrate hens did not differ significantly with
      repeated testing but sham-operated birds were less susceptible to induction by
      the 7th trial when tested daily. In contrast, testing the birds in rapid
      succession had no effect. The possible role of the telencephalon in TI was
      discussed. 

PMID- 24924243
TI  - Undermatching in humans to amount of reinforcement.
AB  - Human subjects were exposed to a concurrent-chain procedure in which amount of
      reinforcement in the terminal links was varied. The experimental procedure was
      designed to resemble as closely as possible animal operant procedures: verbal
      instructions were eliminated, the key-press operant response was shaped, and a
      "consummatory" response was required to receive reward. In addition to varying
      amount of reward, three different pairs of initial-link values in the concurrent
      chain were studied. The human subjects showed undermatching to amount of
      reinforcement (as do animal subjects). Moreover, the degree of undermatching
      tended to increase as the values of the initial links increased, consistent with
      Fantino's delay reduction hypothesis (1977) that choice for a larger reward
      decreases as the length of the initial link increases. 

PMID- 24924244
TI  - A comparison of intradimensional and extradimensional shift learning in pigeons.
AB  - In each of three experiments pigeons were trained on a simultaneous
      discrimination between stimuli that differed in both colour and orientation. For
      half the birds the colour dimension was relevant and for half orientation was
      relevant (i.e., differences along that dimension were correlated with reward and
      nonreward). All birds were then shifted to a second discrimination between new
      colours and orientations. For half this constituted an intradimensional shift in
      that the previously relevant dimension remained relevant; for the remainder the
      previously irrelevant dimension was made relevant (an extradimensional shift).
      Contrary to the predictions of attentional theory, the two types of shift were
      learned with equal ease. 

PMID- 24924245
TI  - Distribution of feeding and drinking by groups of captive house mice.
AB  - Locations of feeding and drinking by social groups of commensal house mice (Mus
      domesticus), were monitored daily for 30 to 90 minutes for 1 to 3 months.
      Eighteen foodcups and 18 water bottles were distributed in a 2.4 * 5.1 m
      population cage. Social groups concentrated their feeding at a few of the
      foodcups which varied among replicates but drank from most of the water bottles.
      A mouse feeding at the same sites that are used by others implies that mice use
      social cues in choosing feeding sites. This is the first documentation of
      socially influenced choice of feeding sites by wild-caught commensal house mice.
      A mouse drinking at several sites without concentrating on any sites implies
      social cues are less important in choosing drinking sites. 

PMID- 24924250
TI  - The age of olfactory cues functioning in chemocommunication among male domestic
      cats.
AB  - In a simulated open-field situation we tried to obtain information about the
      ability of tomcats to distinguish between urine marks of differing ages.
      Reactions to these marks were sniffing, sniffing intensively and "Flehmen". The
      variables we chose to demonstrate a possible discriminatory ability between urine
      marks of different ages were: (1) latency, i.e. the time that elapses between the
      cat's release in the observation arena and the finding of a urine mark, (2) the
      number of occurrences of Flehmen after sniffing, (3) the frequency of sniffing
      and Flehmen, (4) the duration of the first sniffing bout and (5) the occurrence
      of a return to the same scent source during an observation. Our most striking
      observation was that fresh urine marks (maximum age, 4 hours) were explored
      first, before marks more than one day old; the other variables did not differ
      dramatically although we observed a general decline in the intensity of the
      reaction with increasing age of the urine marks. We also found that the visual
      characteristics of a urine mark play an important role, particularly in the
      occurrence of returns. Furthermore we found that the reactions of sniffing and
      Flehmen are linked with an attempt to identify the donor. All results, including
      the possible influence upon marking behaviour of the presence or absence of fresh
      marks, are discussed in the light of the use of a "time plan" spacing mechanism
      by the domestic tomcat as had been suggested in earlier literature. 

PMID- 24924251
TI  - Dominance relations in pairs of domestic cats.
AB  - The dominance relationships in a group of adult male cats were studied by means
      of paired encounters in an observation arena which was equally familiar to both
      animals. In order to develop a good operational technique a pilot study was
      undertaken. Dominance relationships were determined by using criteria based upon
      approach/withdrawal or threatening postures similar to those described by
      Leyhausen (1973). During the encounters two conflicting tendencies seemed to
      appear: efforts to avoid confrontation and agonistic interactions. The intensity
      of the reaction varied from pair to pair. Some kinds of behaviour, not considered
      to be agonistic (such as exploration and, to a lesser extent, rubbing and urine
      marking), were performed more frequently by the dominant male. Furthermore it was
      shown that in the course of the experiments, the number of encounters in which no
      dominance could be assessed increased, probably due to increasing familiarity.
      The results of a pilot study on the effect of castration and testosterone
      treatment upon dominance relationships are also presented. 

PMID- 24924252
TI  - Role of early experience in social behaviour of laboratory-bred female rats.
AB  - Social relationships among female laboratory-bred rats in a community are
      influenced by their early life history. When the rats were born and kept until
      adulthood under conventional breeding conditions, i.e. in single cages, and then
      used to form a community in which they gave birth, one female assumed the
      dominant role, with all others subordinate. The dominant female herded all young
      rats born in the community, irrespective of their age, in a single litter and
      suckled them. She accumulated food and wood shavings from other parts of the
      community near the nest and prevented access to the nest to all other community
      members including other females that had given birth. Subordinate females ceased
      to show maternal behaviour, including lactation, within 24 h (occasionally within
      48 h). The mortality of the young until 15 days of age was high. This type of
      behaviour in a community was observed both with randomly chosen female rats and
      with rats selected as dominant and subordinate types in preceding experiments.
      Female rats born and reared in a community and rats living in a community from 15
      to 30 days of age did not differentiate into dominant and subordinate types. All
      females retained their maternal behaviour, including lactation. Mortality of
      young rats was minimal. In most cases the females built one common nest;
      sometimes each female built her own nest. The results point to the decisive role
      of early experience in the development of maternal behaviour and in the
      occurrence of communal rearing of the young. 

PMID- 24924253
TI  - Self-imposed food deprivation and wheel-running activity in field-trapped Norway
      rats as a function of environmental change, time in captivity and age at capture.
AB  - The tendency of juvenile and adult field-trapped Norway rats (Rattus norvegicus)
      to exhibit self-induced food deprivation in response to changes in their living
      environment was studied after different periods of residency in the laboratory
      environment. Self-imposed food deprivation resulting from the forced occupation
      of a novel environment (activity wheels) was greater for those animals tested
      immediately upon capture and after 25 weeks in captivity than for rats in
      captivity for 4 weeks. The deprivation response of juveniles was less than for
      adults immediately following capture but after 25 weeks in captivity the
      responses of the two age groups were similar. Deprivation responses following
      reintroduction to the home cage environment diminished over time in captivity.
      Wheel-running by adults was greatest immediately following capture whereas
      juveniles continued to show relatively high levels of wheel-running at 4 weeks in
      captivity. The results are discussed in terms of habituation to the laboratory
      environment and time-dependent changes in response to novelty. 

PMID- 24924254
TI  - Social dominance in captive jackdaws (Corvus monedula).
AB  - Social hierarchy was studied in two flocks (14 and 10 individuals, respectively)
      of captive jackdaws. Parent birds acquired high-ranking positions during the
      nesting period. Outside the breeding season the hierarchy seemed to be stable.
      Males generally dominated females. When the top-ranking male arrived at the
      feeding place it tended to supplant one of the feeding birds rather than choose
      an unoccupied site. 

PMID- 24924257
TI  - Wheat germ in vitro translation to produce one of the most toxic sodium channel
      specific toxins.
AB  - Envenoming following scorpion sting is a common emergency in many parts of the
      world. During scorpion envenoming, highly toxic small polypeptides of the venom
      diffuse rapidly within the victim causing serious medical problems. The
      exploration of toxin structure-function relationship would benefit from the
      generation of soluble recombinant scorpion toxins in Escherichia coli. We
      developed an in vitro wheat germ translation system for the expression of the
      highly toxic Aah (Androctonus australis hector)II protein that requires the
      proper formation of four disulphide bonds. Soluble, recombinant N-terminal GST
      (glutathione S-transferase)-tagged AahII toxin is obtained in this in vitro
      translation system. After proteolytic removal of the GST-tag, purified rAahII
      (recombinant AahII) toxin, which contains two extra amino acids at its N terminal
      relative to the native AahII, is highly toxic after i.c.v.
      (intracerebroventricular) injection in Swiss mice. An LD50 (median lethal dose)
      value of 10 ng (or 1.33 pmol), close to that of the native toxin (LD50 of 3 ng)
      indicates that the wheat germ in vitro translation system produces properly
      folded and biological active rAahII. In addition, NbAahII10 (Androctonus
      australis hector nanobody 10), a camel single domain antibody fragment, raised
      against the native AahII toxin, recognizes its cognate conformational epitope on
      the recombinant toxin and neutralizes the toxicity of purified rAahII upon
      injection in mice. 

PMID- 24924258
TI  - Tumor metastasis inhibition by imaging-guided photothermal therapy with single
      walled carbon nanotubes.
AB  - Multi-modal imaging guided photothermal therapy with single-walled carbon
      nanotubes affords effective destruction of primary tumors together with cancer
      cells in sentinel lymph nodes. This results in remarkably prolonged mouse
      survival compared to mice treated by elimination of only the primary tumor by
      either surgery or conventional photothermal therapy. 

PMID- 24924259
TI  - Modeling the shear rate and pressure drop in a hydrodynamic cavitation reactor
      with experimental validation based on KI decomposition studies.
AB  - A mathematical model describing the shear rate and pressure variation in a
      complex flow field created in a hydrodynamic cavitation reactor (stator and rotor
      assembly) has been depicted in the present study. The design of the reactor is
      such that the rotor is provided with surface indentations and cavitational events
      are expected to occur on the surface of the rotor as well as within the
      indentations. The flow characteristics of the fluid have been investigated on the
      basis of high accuracy compact difference schemes and Navier-Stokes method. The
      evolution of streamlining structures during rotation, pressure field and shear
      rate of a Newtonian fluid flow have been numerically established. The simulation
      results suggest that the characteristics of shear rate and pressure area are
      quite different based on the magnitude of the rotation velocity of the rotor. It
      was observed that area of the high shear zone at the indentation leading edge
      shrinks with an increase in the rotational speed of the rotor, although the
      magnitude of the shear rate increases linearly. It is therefore concluded that
      higher rotational speeds of the rotor, tends to stabilize the flow, which in turn
      results into less cavitational activity compared to that observed around 2200
      2500RPM. Experiments were carried out with initial concentration of KI as
      2000ppm. Maximum of 50ppm of iodine liberation was observed at 2200RPM.
      Experimental as well as simulation results indicate that the maximum cavitational
      activity can be seen when rotation speed is around 2200-2500RPM. 

PMID- 24924261
TI  - TP53 mutations in advanced colorectal cancer: the dark side of the moon.
AB  - BACKGROUND: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC)
      is conflicting. METHODS: We assessed TP53 mutations in 51 patients with advanced
      CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil
      (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n
      = 28). RESULTS: Non-functional TP53 mutations were found in 35% of patients. The
      response rate was not significantly different according to TP53 status.
      Progression-free and overall survival were longer in patients with TP53 mutations
      compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs.
      19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation
      was independently associated with a decreased risk of death (hazard ratio 0.329,
      95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in
      influencing outcomes. CONCLUSION: TP53 was not predictive of benefit from first
      line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly
      be associated with a more indolent course of CRC after the diagnosis of
      metastatic disease.

PMID- 24924260
TI  - Clinicians' perceptions and provision of hormonal contraceptives for HIV-positive
      and at-risk women in Southern Africa: an original research article.
AB  - OBJECTIVES: To assess clinician provision of hormonal contraception for HIV
      positive and at-risk women in Southern Africa. STUDY DESIGN: We conducted a
      nationally representative survey of clinicians (n=1444) in HIV-prevalent settings
      in South Africa and Zimbabwe to evaluate evidence-based contraceptive care and
      clinician views of hormonal contraceptives for HIV-positive and at-risk women.
      Multivariable logistic regression was used to analyze differences in
      contraceptive provision by professional training and practice setting. RESULTS:
      Most providers offered oral contraceptives (85%), but only a small minority
      considered them appropriate for women at risk of HIV (27%) or HIV-positive women
      (25%). A higher proportion of clinicians considered injections appropriate for
      women at risk of HIV (42%) or HIV-positive women (46%). Very few considered
      emergency contraceptives appropriate (13%). Multivariable results showed that
      family planning training and clinic as compared to hospital practices were
      associated with evidence-based attitudes about contraception for HIV-positive or
      at-risk women and greater provision. There were no differences, however, between
      physicians and nurses or by HIV training. CONCLUSIONS: These findings emphasize
      the need to improve clinicians' awareness of evidence-based guidelines for
      hormonal contraception for women at high risk of HIV and HIV-positive women.
      Evidence-based information that oral contraception and injections are appropriate
      is essential. Contraceptive education should be integrated into HIV training to
      reach at-risk populations.

PMID- 24924262
TI  - Living with diabetes and hypertension in Tunisia: popular perspectives on
      biomedical treatment.
AB  - OBJECTIVES: The growing prevalence of non-communicable diseases across the Middle
      East and North Africa poses major challenges for underfunded health services.
      This article presents data on the perspectives of ordinary Tunisians who are
      coping with two of these diseases--diabetes and hypertension--and who are
      obtaining treatment through Tunisian public health clinics. Little has been
      written to date on patient experiences of biomedical treatment in Maghreb
      countries. METHODS: Based on qualitative methods and semi-structured interviews
      with 24 patients attending two clinics, one urban and one rural. RESULTS: We
      examine popular aetiological beliefs, ideas about biomedical treatment and its
      implications, and comparative views on the benefits and drawbacks of treatment in
      both public and private clinics. CONCLUSIONS: We highlight two main themes. One
      was nostalgia for a recent past when 'pure' and 'natural' food, 'proper' meals
      and less stressful lives meant less chronic illness, with demanding and costly
      treatment. The other concerned communication in the clinic, and the recurrent
      dismay patients felt at what they saw as the cursory attention and guidance they
      received from clinic staff in public facilities.

PMID- 24924263
TI  - IrFC - An Ixodes ricinus injury-responsive molecule related to Limulus Factor C.
AB  - Limulus Clotting Factor C is a multi-domain serine protease that triggers
      horseshoe crab hemolymph clotting in the presence of trace amounts of bacterial
      lipopolysaccharides. Here we describe and functionally characterize an homologous
      molecule, designated as IrFC, from the hard tick Ixodes ricinus. Tick Factor C
      consists of an N-terminal cysteine-rich domain, four complement control protein
      (sushi) modules, an LCCL domain, a truncated C-lectin domain and a C-terminal
      trypsin-type domain. Developmental expression profiling by quantitative real-time
      PCR revealed that the irfc mRNA is expressed in all stages including eggs. In
      tissues dissected from adult I. ricinus females, the irfc mRNA is present mainly
      in tick hemocytes and accordingly, indirect immunofluorescence microscopy
      localized IrFC intracellularly, in tick hemocytes. Irfc mRNA levels were markedly
      increased upon injection of sterile saline, or different microbes, demonstrating
      that the irfc gene transcription occurs in response to injury. This indicates a
      possible role of IrFC in hemolymph clotting and/or wound healing, although these
      defense mechanisms have not been yet definitely demonstrated in ticks. RNAi
      silencing of irfc expression resulted in a significant reduction in phagocytic
      activity of tick hemocytes against the Gram-negative bacteria Chryseobacterium
      indologenes and Escherichia coli, but not against the yeast, Candida albicans.
      This result suggests that IrFC plays a role in the tick primordial complement
      system and as such possibly mediates transmission of tick-borne pathogens. 

PMID- 24924264
TI  - Using small angle solution scattering data in Xplor-NIH structure calculations.
AB  - This contribution describes the use of small and wide angle X-ray and small angle
      neutron scattering for biomolecular structure calculation using the program Xplor
      NIH, both with and without NMR data. The current algorithms used for calculating
      scattering curves are described, and the use of scattering data as a structural
      restraint is given concrete form as a fragment of an Xplor-NIH structure
      calculation script. We review five examples of the use of scattering data in
      structure calculation, including the treatment of single domain proteins, nucleic
      acids, structure determination of large proteins, and the use of ensemble
      representations to characterize small and large amplitude motions. 

PMID- 24924265
TI  - Multiparametric magnetic resonance imaging of acute experimental brain ischaemia.
AB  - Ischaemia is a condition in which blood flow either drops to zero or proceeds at
      severely decreased levels that cannot supply sufficient oxidizable substrates to
      maintain energy metabolism in vivo. Brain, a highly oxidative organ, is
      particularly susceptible to ischaemia. Ischaemia leads to loss of consciousness
      in seconds and, if prolonged, permanent tissue damage is inevitable. Ischaemia
      primarily results in a collapse of cerebral energy state, followed by a series of
      subtle changes in anaerobic metabolism, ion and water homeostasis that eventually
      initiate destructive internal and external processes in brain tissue. (31)P and
      (1)H NMR spectroscopy were initially used to evaluate anaerobic metabolism in
      brain. However, since the early 1990s (1)H Magnetic Resonance Imaging (MRI),
      exploiting the nuclear magnetism of tissue water, has become the key method for
      assessment of ischaemic brain tissue. This article summarises multi-parametric
      (1)H MRI work that has exploited diffusion, relaxation and magnetisation transfer
      as 'contrasts' to image ischaemic brain in preclinical models for the first few
      hours, with a view to assessing evolution of ischaemia and tissue viability in a
      non-invasive manner. 

PMID- 24924266
TI  - NMR approaches for structural analysis of multidomain proteins and complexes in
      solution.
AB  - NMR spectroscopy is a key method for studying the structure and dynamics of
      (large) multidomain proteins and complexes in solution. It plays a unique role in
      integrated structural biology approaches as especially information about
      conformational dynamics can be readily obtained at residue resolution. Here, we
      review NMR techniques for such studies focusing on state-of-the-art tools and
      practical aspects. An efficient approach for determining the quaternary structure
      of multidomain complexes starts from the structures of individual domains or
      subunits. The arrangement of the domains/subunits within the complex is then
      defined based on NMR measurements that provide information about the domain
      interfaces combined with (long-range) distance and orientational restraints.
      Aspects discussed include sample preparation, specific isotope labeling and spin
      labeling; determination of binding interfaces and domain/subunit arrangements
      from chemical shift perturbations (CSP), nuclear Overhauser effects (NOEs),
      isotope editing/filtering, cross-saturation, and differential line broadening;
      and based on paramagnetic relaxation enhancements (PRE) using covalent and
      soluble spin labels. Finally, the utility of complementary methods such as small
      angle X-ray or neutron scattering (SAXS, SANS), electron paramagnetic resonance
      (EPR) or fluorescence spectroscopy techniques is discussed. The applications of
      NMR techniques are illustrated with studies of challenging (high molecular
      weight) protein complexes. 

PMID- 24924267
TI  - Efficacy of hyaluronic acid spray on swelling, pain, and trismus after surgical
      extraction of impacted mandibular third molars.
AB  - The aim of this study was compare the efficacies of two oral sprays in reducing
      swelling, pain, and trismus after the extraction of impacted mandibular third
      molars. This prospective double-blind, randomized, crossover clinical trial
      included 34 patients with bilateral symmetrically impacted mandibular third
      molars of similar surgical difficulty. Hyaluronic acid or benzydamine
      hydrochloride spray was applied (two pumps) to the extraction area, three times
      daily for 7 days. Swelling was evaluated using a tape measure method, pain with a
      visual analogue scale (VAS), and trismus by measuring the maximum inter-incisal
      opening. Assessments were made on the day of surgery and on days 2 and 7 after
      surgery. Statistically significant differences were detected for the swelling and
      trismus values between the two treatment groups on the second postoperative day
      (P=0.002 and P=0.03, respectively). However, there was no statistically
      significant difference in VAS scores between the two groups. The administration
      of hyaluronic acid spray was more effective than benzydamine hydrochloride spray
      in reducing swelling and trismus. Although no evidence of a reduction in pain
      levels was detected, hyaluronic acid appears to offer a beneficial effect in the
      management of swelling and trismus during the immediate postoperative period
      following impacted third molar surgery. 

PMID- 24924268
TI  - Quality assessment of data discrimination using self-organizing maps.
AB  - MOTIVATION: One of the important aspects of the data classification problem lies
      in making the most appropriate selection of features. The set of variables should
      be small and, at the same time, should provide reliable discrimination of the
      classes. The method for the discriminating power evaluation that enables a
      comparison between different sets of variables will be useful in the search for
      the set of variables. RESULTS: A new approach to feature selection is presented.
      Two methods of evaluation of the data discriminating power of a feature set are
      suggested. Both of the methods implement self-organizing maps (SOMs) and the
      newly introduced exponents of the degree of data clusterization on the SOM. The
      first method is based on the comparison of intraclass and interclass distances on
      the map. Another method concerns the evaluation of the relative number of best
      matching unit's (BMUs) nearest neighbors of the same class. Both methods make it
      possible to evaluate the discriminating power of a feature set in cases when this
      set provides nonlinear discrimination of the classes. AVAILABILITY: Current
      algorithms in program code can be downloaded for free at
      http://mekler.narod.ru/Science/Articles_support.html, as well as the supporting
      data files.

PMID- 24924269
TI  - Methuselah-like genes affect development, stress resistance, lifespan and
      reproduction in Tribolium castaneum.
AB  - Methuselah (Mth) is associated with lifespan, stress resistance and reproduction
      in Drosophila melanogaster, but Mth is not present in nondrosophiline insects. A
      number of methuselah-likes (mthls) have been identified in nondrosophiline
      insects, but it is unknown whether the functions of mth are shared by mthls or
      are divergent from them. Five mthls have been identified in Tribolium castaneum.
      Although they have different developmental expression patterns, they all enhance
      resistance to starvation. Only mthl1 and mthl2 enhance resistance to high
      temperature, whereas mthl4 and mthl5 negatively regulate oxidative stress in T.
      castaneum. Unlike in the fly with mth mutation, knockdown of mthls, except mthl3,
      shortens the lifespan of T. castaneum. Moreover, mthl1 and mthl2 are critical for
      Tribolium development. mthl1 plays important roles in larval and pupal
      development and adult eclosion, while mthl2 is required for eclosion. Moreover,
      mthl1 and mthl2 silencing reduces the fertility of T. castaneum, and mthl1 and
      mthl4 are also essential for embryo development. In conclusion, mthls have a
      significant effect on insect development, lifespan, stress resistance and
      reproduction. These results provide experimental evidence for functional
      divergence among mthls/mth and clues for the signal transduction of Mthls.

PMID- 24924270
TI  - Goal-determined metrics to assess outcomes of esotropia surgery.
AB  - PURPOSE: To report outcomes of esotropia surgery with a goal-determined tool.
      METHODS: A goal-determined outcomes analysis tool was devised to address a
      quality improvement initiative at Boston Children's Hospital. Surgeons
      preoperatively ranked four possible goals for intervention: enhancement of
      binocular potential, restoration of eye contact (reconstructive), management of
      diplopia, and resolution of torticollis. Criteria for success were goal specific;
      the primary outcome measure was surgical success at 2-4 months. Secondary
      outcomes included appraisal of risk factors and a comparison of outcomes with
      this methodology versus traditional criteria for success based on motor
      alignment. No patients were excluded based on diagnosis, systemic and ocular risk
      factors, or intervention performed. RESULTS: A total of 824 patients underwent
      esotropia surgery from 2006 to 2012 and returned for evaluation at 2-4 months'
      follow-up. Of these, 777 had sufficient documentation for inclusion: 372
      procedures were performed primarily to improve binocular potential; 238, to
      restore eye contact; 124, to resolve diplopia; and 43, to remediate torticollis.
      Excellent (71%) or good (13.7%) results were obtained in 84% of cases. Without
      associated risk factors, 75% had excellent and 14% had good outcomes. Risk
      factors were present in 444 (57%). Success diminished with prior strabismus
      surgery (P = 0.004), preoperative angle >=50(Delta) (P = 0.002), and surgery
      before 12 months of age (P = 0.003). Patients having surgery to remediate
      diplopia had the best outcomes (excellent, 79%; good, 8%). Preoperative ranking
      of goals allowed demonstration of better results than would have been reported
      with requirement of "traditional" motor alignment criteria (P = 0.009).
      CONCLUSIONS: Goal-determined methodology can be useful for monitoring outcomes of
      esotropia surgery in diverse populations.

PMID- 24924272
TI  - The relationship of age when motor alignment is achieved and the subsequent
      development of stereopsis in infantile esotropia.
AB  - PURPOSE: To determine the oldest age beyond which the chance of developing
      stereopsis is not possible even with excellent motor alignment in patients with
      infantile esotropia. METHODS: The medical records of children with infantile
      esotropia who underwent a single operation and had alignment within 10(Delta) of
      orthotropia at all follow-up examinations were retrospectively reviewed. Patients
      were assessed for stereopsis after the age of 48 months. RESULTS: A total of 38
      children were included. There was a statistically significant inverse correlation
      between age at surgery and final stereopsis (r = 0.494, P = 0.002). There was a
      significant difference at mean age at surgery between patients having stereopsis
      better than 1000 arcsec and those having no stereopsis (P = 0.002). Post hoc
      power analysis revealed a value of 85%. Receiver operating characteristic curve
      analysis revealed that the optimum cut-off value of the age at surgery for
      predicting stereopsis was 16 months (Youden index = 0.474; area under ROC curve,
      0.784; 95% CI: 0.62-0.90; P = 0.0002). CONCLUSIONS: Surgery for infantile
      esotropia is most likely to result in measureable stereopsis if patient age at
      alignment is not more than 16 months.

PMID- 24924271
TI  - The effectiveness of an autorefractor with eye-tracking capability in pediatric
      patients.
AB  - PURPOSE: To study the diagnostic accuracy and effectiveness in children of a new
      autorefractor with eye-tracking capability. METHODS: Children aged 3-17 years
      were tested with a Marco Nidek ARK-560A autorefractor before and after
      cycloplegia. Cycloplegic manifest refractions were conducted on the more
      cooperative children. Measurements were converted to vector representations M
      (sphere), J0, and J45 (cylinder) by Fourier analysis and compared before and
      after cycloplegia for autorefractor measurements and clinical manifest and
      retinoscopic determinations. RESULTS: A total of 88 subjects were included.
      Autorefractor measurements were successfully obtained on all subjects. Before
      cycloplegia the mean spherical portion of the refractive error by autorefractor
      measurement (AR Dry) averaged 0.29 +/- 0.75 D less hyperopia than the clinical
      manifest refraction (P < 0.005). After cycloplegia, mean autorefractor
      measurements (AR Wet) demonstrated 1.03 +/- 0.84 D more hyperopia in the
      spherical component than AR Dry (P < 0.001). The spherical component of
      autorefraction and clinical measurements after cycloplegia were not statistically
      different, but the J0 astigmatic findings differed by 0.13 D +/- 0.25 (P <
      0.0003). For the 27 children under 8 years of age, precycloplegic autorefractor
      findings differed from manual cycloplegic retinoscopy by 1.48 D +/- 1.13 for
      sphere (P < 0.001) but were not statistically different for astigmatic
      parameters. CONCLUSIONS: Autorefractors can estimate manual retinoscopy values in
      children and may prove useful in the office setting in evaluating pediatric
      patients. Autotracking allowed successful acquisition of measurements in all
      subjects.

PMID- 24924273
TI  - Evaluation and treatment of failed nasolacrimal duct probing in Down syndrome.
AB  - PURPOSE: To elucidate the mechanisms underlying failed nasolacrimal duct (NLD)
      probing in children with Down syndrome (DS) utilizing computed tomography (CT)
      scans and histopathology of nasal mucosa. METHODS: The medical records of
      children with DS and NLD obstruction confirmed by dye disappearance testing who
      failed NLD surgery were retrospectively reviewed. Dimensions of the bony NLD and
      presence of postductal mucosal obstruction were obtained from CT scans.
      Histopathology of the nasal mucosa was performed in a subset of patients.
      Subsequent treatment was topical or intranasal corticosteroids or submucosal
      corticosteroids alone or combined with surgical reduction of the inferior
      turbinate. RESULTS: A total of 9 subjects (age range, 8-10 years) and 43 age
      matched controls were included. Both groups demonstrated a logarithmic increase
      in NLD and maxilla dimensions with increasing age; however, the transverse
      diameter of the NLD was consistently 1-2 mm smaller in children with DS <=5 years
      age (n = 4) than in age-matched controls. The transverse diameter in DS children
      overlapped that of controls after 5 years age. Histopathology revealed abnormal
      lymphoplasmacytic inflammation of the mucosa in 4 of 5 biopsies of DS patients,
      consistent with chronic infection, allergic disease, or immune dysregulation. The
      postductal obstruction was successfully treated with topical or intranasal
      corticosteroids or by surgical reduction of the inferior turbinate submucosa with
      corticosteroid injection. CONCLUSIONS: Before 5 years of age, NLD obstruction in
      children with DS was associated with reduced dimensions of the NLD and
      hypertrophic nasal mucosa. In DS children older than 5 years of age, the
      dimensions of the NLD are normal and postductal obstruction due to hypertrophic
      nasal mucosa should be considered.

PMID- 24924274
TI  - Surgical management of long-standing antielevation syndrome after unilateral
      anterior transposition of the inferior oblique muscle.
AB  - PURPOSE: To investigate surgical management of patients with long-standing
      antielevation syndrome following unilateral anterior transposition of inferior
      oblique muscle. METHODS: We present a series of 3 consecutive patients with
      significant hypotropia several years after unilateral anterior transposition
      surgery. An approach combining denervation-extirpation of the inferior oblique
      muscle and subsequent inferior rectus muscle recession and contralateral superior
      rectus muscle recession was used to manage all 3 patients. RESULTS: Denervation
      extirpation surgery alone or with ipsilateral inferior rectus muscle recession
      were not enough to improve vertical misalignment in these patients. All 3
      patients achieved successful results after denervation-extirpation surgery,
      ipsilateral inferior rectus muscle recession, and contralateral superior rectus
      muscle recession. CONCLUSIONS: In this case series, devervation-extirpation
      surgery on the inferior oblique muscle, ipsilateral inferior rectus recession,
      and contralateral superior rectus recession improved vertical misalignment in
      patients with long-standing antielevation syndrome after unilateral anterior
      transposition of the inferior oblique.

PMID- 24924275
TI  - Hypertropia in unilateral isolated abducens palsy.
AB  - PURPOSE: To evaluate the incidence and features of hypertropia in abducens nerve
      palsy. METHODS: The records of consecutive patients with unilateral, isolated,
      previously unoperated abducens nerve palsy were reviewed for binocular alignment
      on cover testing, Krimsky measurement, or Hess screen testing. Patients with
      associated cranial nerve palsy (including bilateral abducens palsies), orbital
      disease, myasthenia gravis, Horner syndrome, hemiplegia, cerebellar signs,
      arteritis, or previous strabismus surgery were excluded. Control subjects
      underwent complete examination to confirm normality. RESULTS: A total of 79
      patients were included (40 males; mean age 49.2 years). Hypertropia in lateral or
      central gazes was present in 15 of 79 cases (19%) on alternate cover or Krimsky
      testing, in 32 of 56 cases (57%) on Hess screen testing, and absent in all 30
      normal controls. Of cases with hypertropia, the mean of the greatest hypertropia
      in lateral or central gaze on was 5.0(Delta) +/- 2.3(Delta) (standard deviation;
      range, 1(Delta)-8(Delta)) routine clinical examination, and 5.8(Delta) +/-
      4.2(Delta) (range, 2(Delta)-24(Delta)) on Hess screen testing. Of 39 cases with
      partial abducens palsy evaluated by Hess screen testing, the ipsilesional eye was
      hypertropic in 24 (61%) and hypotropic in 15 cases (39%). CONCLUSIONS: Small
      angle hypertropia is common in isolated, unilateral abducens and does not imply
      existence of multiple cranial neuropathies or skew deviation.

PMID- 24924277
TI  - Evaluation of anterior segment parameters using the Pentacam in hyperopic
      anisometropic amblyopic and normal eyes.
AB  - PURPOSE: To evaluate differences in anterior segment parameters using the
      Pentacam between hyperopic anisometropic amblyopic eyes and normal eyes. METHODS:
      The amblyopic and fellow eyes of children with hyperopic anisometropic amblyopia
      and the right eyes of normal control subjects were prospectively evaluated using
      the Pentacam under photopic, scotopic, and cycloplegic conditions. Hyperopic
      anisometropic amblyopia was defined as hyperopia of >=1.5 D, an interocular
      difference of at least 1.5 D in spherical equivalent, and a visual acuity
      difference between the amblyopic and normal eyes of at least 2 lines on the
      Snellen chart. RESULTS: A total of 34 amblyopic subjects and 36 controls were
      included. There were no significant differences in the anterior corneal
      curvature, posterior corneal curvature, central corneal thickness, corneal
      volume, anterior chamber depth, anterior chamber volume, and pupil diameter
      between amblyopic, fellow, and normal eyes (P > 0.05). CONCLUSIONS: In this
      patient cohort the Pentacam detected no significant differences in anterior
      segment parameters in hyperopic anisometropic amblyopic, fellow, and normal eyes
      under photopic, scotopic, and cycloplegic conditions.

PMID- 24924276
TI  - Retinopathy of prematurity and brain damage in the very preterm newborn.
AB  - PURPOSE: To explain why very preterm newborns who develop retinopathy of
      prematurity (ROP) appear to be at increased risk of abnormalities of both brain
      structure and function. METHODS: A total of 1,085 children born at <28 weeks'
      gestation had clinically indicated retinal examinations and had a developmental
      assessment at 2 years corrected age. Relationships between ROP categories and
      brain abnormalities were explored using logistic regression models with
      adjustment for potential confounders. RESULTS: The 173 children who had severe
      ROP, defined as prethreshold ROP (n = 146) or worse (n = 27) were somewhat more
      likely than their peers without ROP to have brain ultrasound lesions or cerebral
      palsy. They were approximately twice as likely to have very low Bayley Scales
      scores. After adjusting for risk factors common to both ROP and brain disorders,
      infants who developed severe ROP were at increased risk of low Bayley Scales
      only. Among children with prethreshold ROP, exposure to anesthesia was not
      associated with low Bayley Scales. CONCLUSIONS: Some but not all of the
      association of ROP with brain disorders can be explained by common risk factors.
      Most of the increased risks of very low Bayley Scales associated with ROP are
      probably not a consequence of exposure to anesthetic agents.

PMID- 24924279
TI  - Anisometropia in children with neurofibromatosis type 1 and unilateral optic
      nerve glioma.
AB  - BACKGROUND: Optic nerve glioma (ONG) occurs in 5% to 25% of individuals with
      neurofibromatosis type 1 (NF1). Recently an association between this lesion and
      unilateral myopia was reported in a series of 4 pediatric patients. The purpose
      of this study was to determine whether unilateral ONG is associated with an
      increased prevalence of anisometropia. METHODS: The medical records of children
      <16 years of age with NF1 disease and unilateral ONG or normal neuroimaging
      examined at Tel-Aviv Medical Center between April 2008 and July 2013 were
      retrospectively reviewed to determine the prevalence of anisometropia and
      anisoastigmatism. RESULTS: A total of 75 children with NF1 disease were included.
      Of these, 25 (11 boys) had a unilateral ONG (mean age, 7.2 years; range, 2-16
      years) and 50 (29 boys) had normal neuroimaging (mean age, 8.3 years; range, 1-15
      years). The mean refraction (spherical equivalent) of eyes with ONG did not
      differ significantly from that of the contralateral eyes (0.74 +/- 1.41 D vs 0.71
      +/- 1.19 D; P = 0.935; 95% CI, -0.710 to 0.770); moreover, there was a high
      correlation between the refraction of eyes with ONG and contralateral eyes (r =
      0.946, P < 0.001). The prevalence of anisometropia in children with ONG and in
      NF1 children with no orbital pathology did not differ significantly (8% vs 16%; P
      = 0.480), and the prevalence of anisoastigmatism was also similar in both groups
      (4% vs 14%, P = 0.255). CONCLUSIONS: ONG in children with NF1 is not associated
      with increased prevalence of anisometropia.

PMID- 24924280
TI  - The Handy Eye Check: a mobile medical application to test visual acuity in
      children.
AB  - PURPOSE: To compare visual acuity results obtained with the Handy Eye Chart to
      results obtained using the Handy Eye Check, a mobile medical application that
      electronically presents isolated Handy Eye Chart optotypes according the
      Amblyopia Treatment Study (ATS) protocol. METHODS: Consecutive patients 6-18
      years of age presenting for eye examinations between May 30, 2012, and June 26,
      2012, were invited to participate. Monocular visual acuity testing was performed
      on the subject's poorer-seeing eye using both the Handy Eye Check and the Handy
      Eye Chart under the same conditions. Visual acuity was first tested using the
      mobile application, then using the chart, followed by repeated application
      testing. Patients were excluded if they were unable to undergo the required
      visual acuity testing or if visual acuity in the worse-seeing eye was less than
      20/200 (for validity testing, but not reliability testing). RESULTS: There was a
      strong linear correlation (r = 0.92) and a mean difference in acuity of -0.005
      logMAR, or less than one letter (95% CI, -0.03 to 0.02), between the two tests.
      The 95% limits of agreement were +/- 2 lines. Test-retest reliability was high,
      with 81% of retest scores within 0.1 logMAR (5 letters) and 100% within 0.2
      logMAR (10 letters), an intraclass correlation coefficient of 0.93, and a
      standard error of measurement of 0.08. CONCLUSIONS: The Handy Eye Check mobile
      application compares similarly to the Handy Eye Chart as a valid and reliable
      test of visual acuity in children age 6-18 years.

PMID- 24924278
TI  - The role of preoperative biometry in selecting initial contact lens power in the
      Infant Aphakia Treatment Study.
AB  - PURPOSE: To investigate the role of preoperative biometry for selecting initial
      contact lens power. METHODS: Patients randomized to receive contact lenses in the
      Infant Aphakia Treatment Study (IATS) were retrospectively analyzed. Inclusion
      criteria were availability of both a preoperative immersion axial length
      measurement and a 1-month postoperative refractive value. The target contact lens
      power for distance was determined using 1-month postoperative spherical
      equivalent refraction (after adjusting for a vertex distance) over the known
      contact lens power. We compared targeted contact lens power for distance with
      three other treatment techniques: (1) 30 D contact lens (32 D minus 2 D
      overcorrection for near vision based on IATS protocol); (2) regression-estimated
      contact lens power of 84.4 - 3.2 * axial length; and (3) IOL power calculated
      using the Sanders-Retzlaff-Kraff (SRK/T) regression formula with a modified A
      constant (112.176). Prediction error (targeted minus estimated contact lens
      power) and its absolute values were calculated. RESULTS: A total of 34 eyes of 34
      patients met inclusion criteria. Age at the time of cataract surgery was 2.4 +/-
      1.7 months. Follow-up refraction was performed at 31 +/- 3 days after surgery.
      Target contact lens power for distance was 26.0 +/- 4.5 D for the IATS cohort
      (which excluded infants with corneal diameter <9 mm). The mean prediction error
      was -4.0, -1.0, and -2.0 D and mean absolute prediction error was 4.4, 2.2, and
      2.9 D, respectively, for 30 D contact lens, regression, and SRK/T-estimated
      power. CONCLUSIONS: Preoperative biometry can be used to estimate contact lens
      power for distance if an accurate refraction cannot be obtained initially.

PMID- 24924281
TI  - Long-term treatment results of accommodative esotropia.
AB  - PURPOSE: To report the long-term ocular alignment outcomes of patients with
      accommodative esotropia. METHODS: The medical records of consecutive patients
      <=12 year of age diagnosed with refractive accommodative esotropia (esotropia
      eliminated or decreased to within 10(Delta) with full hyperopic correction) and
      followed for at least 10 years were retrospectively reviewed. RESULTS: A total of
      107 patients were included (mean age, 4.81 +/- 2.64 years). The mean follow-up
      period was 12.02 +/- 2.25 years (range, 10-21 years). At the first examination
      performed 10 years after spectacle correction (mean, 10.2 years), 85 patients
      (79%) had orthophoria or esotropia <=10(Delta) at both near and distance
      fixation, 14 (13%) had consecutive exotropia, 5 (5%) had decompensation and 3
      (3%) had esotropia with a high ratio of accommodative convergence to
      accommodation (AC/A). The mean time interval between presentation and
      prescription of full hyperopic correction, initial cycloplegic refraction, and
      presence of amblyopia was not associated with consecutive exotropia,
      decompensation, or a high AC/A ratio esotropia. CONCLUSIONS: Whereas most
      patients with refractive accommodative esotropia maintained normal long-term
      ocular motility with spectacle treatment, some developed consecutive exotropia,
      nonaccommodative esotropia, or esotropia with a high AC/A ratio.

PMID- 24924282
TI  - Risk and clinical course of retinopathy of prematurity in 78 infants of
      gestational age 22-25 weeks.
AB  - PURPOSE: To characterize the retinopathy of prematurity (ROP) and survival of
      infants born at gestational age (GA) of 22-25 weeks. METHODS: This study was a
      comparative case series for the total set of 78 infants <=25 GA screened for ROP
      at a level IV NICU during a 21-month period. Data are presented on infants
      screened for ROP from 6 weeks after birth for 22 and 23 weeks' GA infants and
      from 5 weeks after birth for 24 and 25 weeks' GA. Accounting for the competing
      risk of mortality, we implemented Cox CR regression models to assess birth
      weight, GA, and admission diagnosis as potential risk factors for the following
      time to event outcomes: type 1 disease, aggressive posterior ROP (AP-ROP), plus
      disease, first presentation of ROP, and worst ROP observed. RESULTS: Risk of
      laser treatment (subhazard ratio [SHR] = 0.56, P = 0.007) and of plus disease
      (SHR = 0.49, P = 0.001) was increased among those born at lower GA. Twenty
      infants required laser for type 1 disease at median postmenstrual age (PMA) of
      35.8 weeks (range, 33.0-42.7); infants with AP-ROP had laser at PMA of 34.5 weeks
      (range, 33.0-36.9), 2 weeks earlier than infants without AP-ROP at PMA 36.5 weeks
      (range, 33.9-42.7). The cumulative probability of receiving laser therapy
      approached 46% (22 or 23 weeks' GA), 30% (24 weeks' GA), and 18% (25 weeks' GA).
      CONCLUSIONS: The 2013 screening guidelines appear to be appropriate for infants
      of 22 and 23 weeks' GA when ROP screening begins at PMA 31 weeks.

PMID- 24924283
TI  - The effect of adding orbital computed tomography findings to the Chandler
      criteria for classifying pediatric orbital cellulitis in predicting which
      patients will require surgical intervention.
AB  - PURPOSE: To assess the effect of adding orbital computerized tomography (CT)
      findings to the Chandler criteria for classifying pediatric orbital cellulitis in
      predicting which patients will require surgical intervention. METHODS: The
      medical records of patients with orbital CT at a tertiary pediatric hospital from
      January 2000 to March 2011 were reviewed retrospectively. CT images of cases with
      radiology report of postseptal orbital involvement were further reviewed by a
      neuroradiologist. RESULTS: Of 101 cases of orbital cellulitis, 71 (mean age, 7.1
      +/- 4.0) were successfully managed with systemic antibiotics alone; 30 patients
      (mean age, 7.2 +/- 4.3) required surgical intervention. Bony destruction on CT
      was significantly associated with surgical intervention (P = 0.02), and the size
      of the subperiosteal abscess (SPA) was significantly correlated with management
      outcome. Patients who were managed with systemic antibiotics alone had a mean SPA
      volume of 2.1 +/- 2.4 mL; those who had undergone surgical intervention had a
      mean SPA volume of 14.3 mL +/- 16.8 mL (P < 0.0001). If SPA volume is <3.8 mL,
      then the probability of surgery is 12%; if SPA is >3.8 mL, the probability of
      surgery is 71% (P < 0.0001). CONCLUSIONS: Adding radiological characteristics
      such as presence of bony destruction on CT and size of SPA to the Chandler
      orbital cellulitis classification scheme increases the ability to more accurately
      predict which patients will require surgical intervention.

PMID- 24924284
TI  - Adjustable sutures in children.
AB  - Although adjustable sutures are considered a standard technique in adult
      strabismus surgery, most surgeons are hesitant to attempt the technique in
      children, who are believed to be unlikely to cooperate for postoperative
      assessment and adjustment. Interest in using adjustable sutures in pediatric
      patients has increased with the development of surgical techniques specific to
      infants and children. This workshop briefly reviews the literature supporting the
      use of adjustable sutures in children and presents the approaches currently used
      by three experienced strabismus surgeons.

PMID- 24924285
TI  - Retinal telangiectasis detected during a vision screening examination in a child
      with hearing loss led to the diagnosis of facioscapulohumeral muscular dystrophy.
AB  - A 2-year-old girl with congenital sensorineural hearing loss was found to have
      retinal exudation and subretinal fluid in her left eye. Further investigation
      revealed leaking retinal telangiectasias in her left eye and extensive areas of
      peripheral retinal nonperfusion in both eyes. A clinical diagnosis of
      facioscapulohumeral muscular dystrophy (FSHD) was confirmed by genetic testing.
      The patient was followed with serial intraoperative optical coherence tomography
      (OCT) scans, which demonstrated subretinal fluid in the macula and its subsequent
      resolution after treatment. She underwent 6 rounds of panretinal photocoagulation
      and 2 injections of intravitreal bevacizumab, which resolved the subretinal fluid
      and exudates. 

PMID- 24924286
TI  - Pharmacotherapy for weight loss: the cardiovascular effects of the old and new
      agents.
AB  - WHAT IS KNOWN AND OBJECTIVE: Obesity affects approximately one-third of the
      American population, and its prevalence continues to increase. It is a
      significant risk factor for cardiovascular diseases and contributes to increased
      healthcare costs and mortality. The objective is to review the current literature
      on the cardiovascular effects of weight loss pharmacotherapy agents. METHODS:
      Literature was accessed through MEDLINE/PubMed (up to April 2013) using the
      search terms obesity, weight loss, pharmacotherapy, cardiovascular adverse
      effects and cardiovascular side effects. References of the articles identified
      and www.clinicaltrials.gov were also reviewed. Relevant guidelines, review
      articles, clinical trials, meta-analyses, case series, FDA documentation and
      prescribing information were included and limited to English language articles.
      RESULTS AND DISCUSSION: With the newly FDA-approved weight loss pharmacotherapy,
      treatment options for obesity are more diverse. However, safety concerns,
      including adverse cardiovascular effects, have played a significant role in the
      history of weight loss pharmacotherapy and will likely play a role in the future
      of the new agents, lorcaserin and phentermine/topiramate, as well. WHAT IS NEW
      AND CONCLUSION: Long-term cardiovascular outcomes studies with and without high
      risk cardiovascular patients are still needed for both lorcaserin and
      phentermine/topiramate before these agents can be recommended in these patient
      populations. It is yet to be determined whether modest weight loss benefit of
      these new agents outweighs the cardiovascular risks.

PMID- 24924287
TI  - New cholinesterase inhibitors from Garcinia atroviridis.
AB  - A triflavanone, Garcineflavanone A (1) and a biflavonol, Garcineflavonol A (2)
      have been isolated from the stem bark of Garcinia atroviridis (Clusiaceae),
      collected in Peninsular Malaysia. Their structures were established using one and
      two-dimensional NMR, UV, IR and mass spectrometry and evaluated in vitro for
      their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes
      inhibitory activity. Molecular docking studies of the isolated compounds were
      performed using docking procedure of AutoDock to disclose the binding interaction
      and orientation of these molecules into the active site gorge. 

PMID- 24924288
TI  - Leonurine ameliorates LPS-induced acute kidney injury via suppressing ROS
      mediated NF-kappaB signaling pathway.
AB  - Acute kidney injury (AKI) is an abrupt loss of kidney function. Severe AKI
      requires renal replacement therapy and has high mortality. Leonurine (LEO), an
      alkaloid isolated from Leonurus cardiaca, has shown biological effects such as
      antioxidant, anticoagulant, and anti-apoptosis. We have examined the effect of
      LEO on lipopolysaccharide (LPS)-induced AKI in mice and further studied the
      mechanism involved. Blood urea nitrogen (BUN), creatinine and cytokine were
      estimated in the serum or tissue. Kidney tissue specimens were used for
      biochemical estimations of lipid peroxides (LPO), reduced glutathione (GSH), and
      reactive oxygen species (ROS). The effects of LEO on LPS-induced renal tissue
      damage were detected by hematoxylin and eosin (HE) stain and electron microscopy.
      The production of cytokines in the tissue and blood was measured by ELISA.
      Protein phosphorylation and protein subcellular localization were tested by
      Western blot. LEO is protected against LPS-induced AKI, improved animal survival
      and maintained the redox balance. The beneficial effects of LEO were accompanied
      by the down-regulation of TNF-alpha, IL-1, IL-6, IL-8, KIM-1 expression and by
      the inhibition of the phosphorylation of IkappaBalpha and p65 translocalization.
      These results suggest that LEO may suppress NF-kappaB activation and inhibit pro
      inflammatory cytokine production via decreasing cellular ROS production.
      Accumulating studies have demonstrated that LEO reduces kidney injury and
      protects renal functions from LPS-induced kidney injury. 

PMID- 24924289
TI  - Synthesis and biological evaluation of pyranoisoflavone derivatives as anti
      inflammatory agents.
AB  - In this paper, barbigerone (1a) and its twenty-seven related structural analogues
      were synthesized via complementary synthetic routes and their anti-inflammatory
      effects on the expression of TNF-alpha in LPS-stimulated splenocytes were
      evaluated. Among these compounds, 1a, 1d, 1f and 1g were found to remarkably
      inhibit TNF-alpha production. Furthermore, 1g showed the most potent and dose
      dependent manner inhibitory effect on TNF-alpha release, with better IC50 value
      (3.58 MUM) than barbigerone (8.46 MUM). Oral administration of 1g at 20 mg/kg/day
      for two weeks obviously demonstrated protective effect in adjuvant-induced
      arthritis models as evaluated by clinical score of paws, and histological
      examination of joint tissues from rats. Mechanism studies on mRNA and protein
      level suggested that 1g inhibited the TNF-alpha production via depressing TNF
      alpha converting enzyme (TACE) mRNA expression. In conclusion, these data show 1g
      with potential therapeutic effects as an anti-inflammatory agent.

PMID- 24924290
TI  - Wild celery (Smyrnium olusatrum L.) oil and isofuranodiene induce apoptosis in
      human colon carcinoma cells.
AB  - Smyrnium olusatrum (Apiaceae), well known as wild celery, is a biennal celery
      scented plant used for many centuries as a vegetable, then abandoned after the
      introduction of celery. In the present work, the essential oil obtained from
      inflorescences and the amounts of its main constituents isofuranodiene, curzerene
      and germacrone were analyzed by GC as well as by HPLC because of their
      degradation (Cope rearrangement) occurring at high temperatures. The oil and the
      main constituents were assayed for cytotoxic activity on the human colon cancer
      cell line (HCT116) by MTT assay. Flower oil and isofuranodiene showed noteworthy
      activity on tumor cells with IC50 of 10.71 and 15.06 MUg/ml, respectively.
      Analysis of the cytotoxic activity showed that wild celery oil and isofuranodiene
      are able to induce apoptosis in colon cancer cells in a time and concentration
      dependent manner suggesting a potential role as models for the development of
      chemopreventive agents.

PMID- 24924291
TI  - Extended transmission of two H5/H7 low pathogenic avian influenza viruses in
      chickens.
AB  - Transmission experiments are useful for investigating the mechanisms of low
      pathogenic notifiable avian influenza virus (LPNAI) transmission. In this study,
      the hypothesis that inoculation-infected chickens are more infectious than
      contact-infected chickens was tested. To this end, extended transmission
      experiments with one H5N2 and one H7N1 LPAIV which had previously been
      characterized in a series of standard transmission experiments were conducted in
      specific pathogen-free (SPF) chickens. For the H5N2 LPAIV, the infectivity of
      contact-infected chickens was similar to the infectivity of inoculated chickens.
      Despite results from a previous study suggesting the H7N1 LPAIV strain to be
      similarly infectious to SPF chickens as the H5N2 LPAIV strain, the acquisition of
      contact-infected chickens proved more difficult for H7N1 LPAIV. It was assumed
      that this might have been a consequence of the length and timing of the exposure
      period. In conclusion, for LPNAIVs that first seemed equally infectious, short
      term transmissibility may vary considerably.

PMID- 24924292
TI  - A three-year randomized controlled trial in 6-year-old children on caries
      preventive strategies in a general dental practice in the Netherlands.
AB  - A parallel-randomized controlled trial on caries-preventive strategies was
      conducted in a general dental practice with a mixed socioeconomic background
      patient population. The aim of this study was to test the hypothesis that,
      compared to regular care consisting of check-ups twice a year with professional
      fluoride applications and pit and fissure sealants in all permanent molars, a
      larger caries-preventive effect can be achieved by following a non-operative
      caries treatment and prevention (NOCTP) strategy or by following, in addition to
      regular care, an increased number of professional topical fluoride applications
      (IPFA). A total of 230 children (6.0 years +/- 3 months of age) were randomly
      assigned to the two experimental groups or the control group. After 3 years, 179
      participants remained in the study (54 NOCTP, 62 IPFA and 63 control). The
      children were examined at baseline and at 3 years by the same experienced
      examiner, who was blinded for the allocation of the children. Caries was scored
      clinically at the D3 level. Per protocol analysis revealed a mean DMFS increment
      after 3 years of 0.15 (95% CI -0.05 to 0.35) for NOCTP, 0.34 (95% CI 0.11 to
      0.54) for IPFA and 0.47 (95% CI 0.26 to 0.68) for the control group. To account
      for missing data, multiple imputation was used, after which the mean DMFS
      increment was 0.11 (95% CI -0.05 to 0.27) for NOCTP, 0.29 (95% CI 0.11 to 0.46)
      for IPFA and 0.40 (95% CI 0.21 to 0.55) for the control group. Testing the
      differences with independent samples t test revealed a lower caries increment in
      the NOCTP group compared to the control group. ANCOVA was used to correct for
      differences in baseline dmfs, socioeconomic status and perceived dental hygiene
      burden. The DeltaDMFS effect size between the NOCTP and the control group
      dropped, losing statistical significance (p = 0.06). Although the results in this
      study are promising, it has yet to be established in a larger study whether NOCTP
      has the ability to be effective in regular dental practice with a mixed
      socioeconomic status population.

PMID- 24924293
TI  - Evaluation of an imaging biomarker, Dixon quantitative chemical shift imaging, in
      Gaucher disease: lessons learned.
AB  - Gaucher disease (GD) is the first lysosomal storage disorder for which specific
      therapy became available. The infiltration of bone marrow by storage cells plays
      an important part in the pathophysiology of skeletal complications and can be
      quantified by measurements of bone marrow fat fraction (Ff). Ff measurements by
      Dixon quantitative chemical shift imaging (QCSI) are standard for the follow-up
      care of GD patients at the Academic Medical Center. Several criteria should be
      met in order for these measurements to qualify as an imaging biomarker. These
      include: 1) The presence of the imaging biomarker is closely coupled or linked to
      the presence of the target disease or condition; 2) The detection and/or
      quantitative measurement of the biomarker is accurate, reproducible, and feasible
      over time, and; 3) The changes measured over time in the imaging biomarker are
      closely coupled, or linked, to the success or failure of the therapeutic effect
      and the true end point for the medical therapy being evaluated. This review
      assesses the use of Ff measurements by QCSI as a biomarker for GD in light of
      these criteria. In addition potential pitfalls are discussed including:
      degenerative disc disease; vertebral collapse and infection; haematological
      malignancies; focal fatty deposits; age; menopause; phase and repositioning
      errors, and; fat surrounding the basivertebral vein.QCSI measurements of Ff can
      be used as an imaging biomarker for GD taking these pitfalls into account. It is
      one of the first biomarkers, in particular imaging biomarkers, for GD that has
      been systematically evaluated and could be a valuable tool in clinical trials
      comparing different treatments or dosing regimens. 

PMID- 24924294
TI  - Assessment of the lateral patellar facet in varus arthritis of the knee.
AB  - BACKGROUND: Lateral patellar arthritis has been associated with poor outcomes in
      unicompartmental knee arthroplasty. The current study correlates intraoperative
      findings with MRI imaging, skyline radiographs and the presence of anterior knee
      pain. METHODS: In 92 consecutive knees with varus arthritis, the patellofemoral
      compartment was assessed during surgery, on skyline radiographs and on MRI.
      Anterior knee pain was recorded on a visual-analog-scale. Intraoperative
      assessment was based on the Outerbridge grading scale. Skyline radiographs were
      evaluated according to the Ahlback grading scale; MRIs were assessed according to
      a modified Outerbridge grading scale. RESULTS: There was an excellent correlation
      (rs=0.833; p<0.001) in the cartilage assessment of the lateral patellar facet
      between MRI and surgery. A good correlation (rs=0.664; p<0.001) was seen between
      Ahlback Grades and macroscopic Outerbridge Grades of the lateral patella. Ahlback
      Grades and MRI modified Outerbridge Grades showed a good correlation (rs=0.643;
      p<0.001) for the lateral patella. Twelve percent of knees (seven out of 60) with
      Ahlback Grade 0 or 1 and mild to moderate anterior knee pain had a macroscopic
      Outerbridge Grade of 3 on the lateral patella. None of these 60 knees had a full
      thickness cartilage defect on MRI. CONCLUSION: Normal skyline radiographs in
      patients with mild to moderate anterior knee pain can rule out full-thickness
      cartilage defects of the lateral patellar facet as observed during surgery and on
      MRI. The MRI allows for the most accurate assessment of the patellofemoral joint
      and is warranted in all patients with radiographic abnormalities or severe
      anterior knee pain. LEVEL OF EVIDENCE: Diagnostic study, Level II.

PMID- 24924295
TI  - Success or failure of critical steps in community case management of malaria with
      rapid diagnostic tests: a systematic review.
AB  - BACKGROUND: Malaria still causes high morbidity and mortality around the world,
      mainly in sub-Saharan Africa. Community case management of malaria (CCMm) by
      community health workers (CHWs) is one of the strategies to combat the disease by
      increasing access to malaria treatment. Currently, the World Health Organization
      recommends to treat only confirmed malaria cases, rather than to give presumptive
      treatment. OBJECTIVES: This systematic review aims to provide a comprehensive
      overview of the success or failure of critical steps in CCMm with rapid
      diagnostic tests (RDTs). METHODS: The databases of Medline, Embase, the Cochrane
      Library, the library of the 'Malaria in Pregnancy' consortium, and Web of Science
      were used to find studies on CCMm with RDTs in SSA. Studies were selected
      according to inclusion and exclusion criteria, subsequently risk of bias was
      assessed and data extracted. RESULTS: 27 articles were included. CHWs were able
      to correctly perform RDTs, although specificity levels were variable. CHWs showed
      high adherence to test results, but in some studies a substantial group of RDT
      negatives received treatment. High risk of bias was found for morbidity and
      mortality studies, therefore, effects on morbidity and mortality could not be
      estimated. Uptake and acceptance by the community was high, however negative
      tested patients did not always follow up referral advice. Drug or RDT stock-outs
      and limited information on CHW motivation are bottlenecks for sustainable
      implementation. RDT-based CCMm was found to be cost effective for the correct
      treatment of malaria in areas with low to medium malaria prevalence, but study
      designs were not optimal. DISCUSSION: Trained CHWs can deliver high quality care
      for malaria using RDTs. However, lower RDT specificity could lead to missed
      diagnoses of non-malarial causes of fever. Other threats for CCMm are non
      adherence to negative test results and low referral completion. Integrated CCM
      may solve some of these issues. Unfortunately, morbidity and mortality are not
      adequately investigated. More information is needed about influencing
      sociocultural aspects, CHW motivation and stock supply. CONCLUSION: CCMm is
      generally well executed by CHWs, but there are several barriers for its success.
      Integrated CCM may overcome some of these barriers.

PMID- 24924296
TI  - Risk factors associated with lipomyelomeningocele: a case-control study.
AB  - BACKGROUND: In general, it seems that both genetic and environmental factors play
      important roles in the induction of neural tube defects. Lipomyelomeningocele
      (LipoMMC) is a rather common type of closed neural tube defect, but only limited
      studies have investigated the potential risk factors of this anomaly. Therefore,
      the purpose of this case-control study was to investigate the risk factors
      involved in LipoMMC formation. MATERIAL AND METHOD: Various risk factors were
      evaluated in 35 children between 1 month and 10 years of age with LipoMMC in a
      hospital-based case-control study. The 2 control arms consisted of 35 children
      with myelomeningocele (MMC group) and 35 children with congenital anomalies other
      than central nervous system problems (control group). All groups were matched for
      age and visited the same hospital. A structured questionnaire was used for the
      collection of all data, including the mothers' weight and height during
      pregnancy, education, reproductive history, previous abortions, and socioeconomic
      status, as well as the parents' consanguinity and family history of the same
      anomalies. RESULTS: Univariate analysis of the children with LipoMMC compared to
      the control group showed that the use of periconceptional folic acid
      supplementation was significantly lower in the MMC and LipoMMC groups compared to
      the control group. In addition, comparison of the MMC and control groups revealed
      statistically significant differences regarding the use of folic acid and
      maternal obesity. In multivariate analysis, use of folic acid in the
      periconceptional period and during the first trimester was an independent risk
      factor for LipoMMC and MMC. Furthermore, maternal obesity was a significantly
      positive risk factor for MMC. CONCLUSION: The probable risk factors for LipoMMC
      were investigated in this case-control study. Consumption of folic acid in the
      periconceptional period and during the first trimester is an independent
      protective factor against LipoMMC. It seems that larger studies are needed to
      examine other possible risk factors.

PMID- 24924297
TI  - Proteomic analysis of proteins related to rice grain chalkiness using iTRAQ and a
      novel comparison system based on a notched-belly mutant with white-belly.
AB  - BACKGROUND: Grain chalkiness is a complex trait adversely affecting appearance
      and milling quality, and therefore has been one of principal targets for rice
      improvement. Eliminating chalkiness from rice has been a daunting task due to the
      complex interaction between genotype and environment and the lack of molecular
      markers. In addition, the molecular mechanisms underlying grain chalkiness
      formation are still imperfectly understood. RESULTS: We identified a notched
      belly mutant (DY1102) with high percentage of white-belly, which only occurs in
      the bottom part proximal to the embryo. Using this mutant, a novel comparison
      system that can minimize the effect of genetic background and growing environment
      was developed. An iTRAQ-based comparative display of the proteins between the
      bottom chalky part and the upper translucent part of grains of DY1102 was
      performed. A total of 113 proteins responsible for chalkiness formation was
      identified. Among them, 70 proteins are up-regulated and 43 down-regulated.
      Approximately half of these differentially expressed proteins involved in central
      metabolic or regulatory pathways including carbohydrate metabolism (especially
      cell wall synthesis) and protein synthesis, folding and degradation, providing
      proteomic confirmation of the notion that chalkiness formation involves diverse
      but delicately regulated pathways. Protein metabolism was the most abundant
      category, accounting for 27.4% of the total differentially expressed proteins. In
      addition, down regulation of PDIL 2-3 and BiP was detected in the chalky tissue,
      indicating the important role of protein metabolism in grain chalkiness
      formation. CONCLUSIONS: Using this novel comparison system, our comprehensive
      survey of endosperm proteomics in the notched-belly mutant provides a valuable
      proteomic resource for the characterization of pathways contributing to
      chalkiness formation at molecular and biochemical levels.

PMID- 24924300
TI  - An efficient and extendable python library to analyze neuronal morphologies.

PMID- 24924298
TI  - Expression and regulation of triggering receptor expressed on myeloid cells 1 in
      periodontal diseases.
AB  - Periodontitis is an inflammatory infectious disease that destroys the tooth
      supporting tissues. It is caused by multi-species subgingival biofilms that
      colonize the tooth surface. Porphyromonas gingivalis, Treponema denticola and
      Tannerella forsythia (i.e. 'red complex' bacteria) are characteristic subgingival
      biofilm species. The triggering receptor expressed on myeloid cells 1 (TREM-1) is
      a cell surface receptor of the immunoglobulin superfamily, with a role in the
      amplification of proinflammatory cytokine production during infection. This study
      aimed to investigate TREM-1 mRNA expression in gingival tissues from patients
      with chronic periodontitis, generalized aggressive periodontitis and healthy
      subjects and its correlation with the levels of periodontal pathogens in the
      tissue. A further aim was to investigate the regulation of TREM-1 in human
      monocytic cells (MM6) challenged with an in-vitro subgingival biofilm model.
      Gingival tissue TREM-1 expression was increased in both chronic and aggressive
      periodontitis, compared to health, and correlated with the levels of the 'red
      complex' species in the tissue. No significant differences were detected between
      the two forms of periodontitis. Biofilm-challenged MM6 cells exhibited higher
      TREM-1 expression and secretion compared to controls, with partial involvement of
      the 'red complex'. Engagement or inhibition of TREM-1 affected the capacity of
      the biofilms to stimulate interleukin (IL)-1beta, but not IL-8, secretion by the
      cells. In conclusion, this study reveals that TREM-1 tissue expression is
      enhanced in periodontal disease, and correlates with the level of periodontal
      pathogens. It also provides a mechanistic insight into the regulation of TREM-1
      expression and the associated IL-1beta production in biofilm-challenged
      monocytes. 

PMID- 24924301
TI  - Government insists safeguards for patients who lack mental capacity are workable.

PMID- 24924302
TI  - A shared regulatory perspective on deferral from blood donation of men who have
      sex with men (MSM).
AB  - National Regulatory Authorities (NRAs) establish deferral criteria for donors
      with risk factors for transfusion transmissible infections (TTI). In most
      jurisdictions, epidemiological data show that men who have sex with men (MSM)
      have a significantly higher rate of TTI than the general population.
      Nevertheless, changes from an indefinite donor deferral for MSM have been
      considered in many countries in response to concerns over a perceived
      discrimination and questioning of the scientific need. Changes to MSM donor
      deferral criteria should be based on sound scientific evidence. Safety of
      transfusion recipients should be the first priority, and stakeholder input should
      be sought. 

PMID- 24924303
TI  - RETRACTED ARTICLE: Transkorneale Elektrostimulation bei Patienten mit primarem
      Offenwinkelglaukom.

PMID- 24924304
TI  - Risks of malignant and non-malignant tumours in tall women treated with high-dose
      oestrogen during adolescence.
AB  - BACKGROUND/AIM: High-dose oestrogen treatment has been used to reduce growth in
      tall adolescent girls. The long-term safety with regard to cancer has not been
      clarified. Our aim was to study if this growth reduction therapy affects cancer
      risk later in life. METHODS: A cohort study of 369 (172 treated, 197 untreated)
      Swedish women who in 1973-1993 were assessed for tall adolescent stature was
      designed. Data were collected from university hospital records, patient
      questionnaires, and the Swedish Cancer Register. RESULTS: Risks are presented as
      odds ratios (ORs) with 95% confidence intervals comparing treated to untreated
      subjects. In treated subjects, the overall OR for having a tumour (malignant or
      non-malignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours,
      0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-infinity) for melanoma.
      When limiting to malignant tumours, the crude ORs were of similar magnitude.
      CONCLUSION: The OR for any melanoma was higher in treated than in untreated
      women, suggesting an increased risk of melanoma associated with high-dose
      oestrogen treatment during adolescence. Although the risk estimates were
      increased for overall tumours, breast tumours, malignant gynaecological tumours,
      and malignant melanoma, these associations were not statistically significant.
      Our results need to be verified in a larger cohort.

PMID- 24924306
TI  - Abstracts from the 3rd World Congress on Vascular Access, WoCoVA 2014, 18-20 June
      2014, Berlin, Germany.
AB  - Abstracts from the 3rd World Congress on Vascular Access, WoCoVA 2014, Berlin -
      Germany, 18-20 June 2014. 

PMID- 24924305
TI  - Novel Nystatin A1 derivatives exhibiting low host cell toxicity and antifungal
      activity in an in vitro model of oral candidosis.
AB  - Opportunistic oral infections caused by Candida albicans are frequent problems in
      immunocompromised patients. Management of such infections is limited due to the
      low number of antifungal drugs available, their relatively high toxicity and the
      emergence of antifungal resistance. Given these issues, our investigations have
      focused on novel derivatives of the antifungal antibiotic Nystatin A1, generated
      by modifications at the amino group of this molecule. The aims of this study were
      to evaluate the antifungal effectiveness and host cell toxicity of these new
      compounds using an in vitro model of oral candidosis based on a reconstituted
      human oral epithelium (RHOE). Initial studies employing broth microdilution,
      revealed that against planktonic C. albicans, Nystatin A1 had lower minimal
      inhibitory concentration than novel derivatives. However, Nystatin A1 was also
      markedly more toxic against human keratinocyte cells. Interestingly, using
      live/dead staining to assess C. albicans and tissue cell viability after RHOE
      infection, Nystatin A1 derivatives were more active against Candida with lower
      toxicity to epithelial cells than the parent drug. Lactate dehydrogenase activity
      released by the RHOE indicated a fourfold reduction in tissue damage when certain
      Nystatin derivatives were used compared with Nystatin A1. Furthermore, compared
      with Nystatin A1, colonisation of the oral epithelium by C. albicans was notably
      reduced by the new polyenes. In the absence of antifungal agents, confocal laser
      scanning microscopy showed that C. albicans extensively invaded the RHOE.
      However, the presence of the novel derivatives greatly reduced or totally
      prevented this fungal invasion. 

PMID- 24924307
TI  - Conformation-specific circular dichroism spectroscopy of cold, isolated chiral
      molecules.
AB  - The CD spectroscopy of a chiral compound in solution yields an average CD value
      derived from all of the conformations of a chiral molecule. By contrast, CD
      spectroscopy of cold chiral molecules in the gas phase distinguishes specific
      conformers of a chiral molecule, but the weak CD effect has limited the practical
      application of this technique. Reported herein is the first resonant two-photon
      ionization CD spectra of ephedrines in a supersonic jet using circularly
      polarized laser pulses, which were generated by synchronizing the oscillation of
      the photoelastic modulator with the laser firing. The spectra exhibited well
      resolved CD bands which were specific for the conformations and vibrational modes
      of each enantiomer. The CD signs and magnitudes of the jet-cooled chiral
      molecules were very sensitive to their conformations and thus offered crucial
      information for determining the three-dimensional structures of chiral species,
      as conducted in combination with quantum chemical calculations. 

PMID- 24924308
TI  - Laminated carbon nanotube networks for metal electrode-free efficient perovskite
      solar cells.
AB  - Organic-inorganic metal halide perovskite solar cells were fabricated by
      laminating films of a carbon nanotube (CNT) network onto a CH3NH3PbI3 substrate
      as a hole collector, bypassing the energy-consuming vacuum process of metal
      deposition. In the absence of an organic hole-transporting material and metal
      contact, CH3NH3PbI3 and CNTs formed a solar cell with an efficiency of up to
      6.87%. The CH3NH3PbI3/CNTs solar cells were semitransparent and showed
      photovoltaic output with dual side illuminations due to the transparency of the
      CNT electrode. Adding spiro-OMeTAD to the CNT network forms a composite electrode
      that improved the efficiency to 9.90% due to the enhanced hole extraction and
      reduced recombination in solar cells. The interfacial charge transfer and
      transport in solar cells were investigated through photoluminescence and
      impedance measurements. The flexible and transparent CNT network film shows great
      potential for realizing flexible and semitransparent perovskite solar cells. 

PMID- 24924310
TI  - Pharmacokinetic plasma behaviors of intravenous and oral bioavailability of
      thymoquinone in a rabbit model.
AB  - Thymoquinone (THQ), the active constituent of Nigella sativa seeds, has
      demonstrated some potential pharmacological activities. The present study was
      designed to investigate the pharmacokinetic behavior of THQ following intravenous
      (IV) and oral (PO) administration using an animal model. THQ was given vascularly
      (5 mg/kg IV) and extravascularly (20 mg/kg PO) to Vole rabbits, and blood samples
      were collected at predetermined time points. The concentrations of THQ in plasma
      were measured by a high-performance liquid chromatography, and the
      pharmacokinetic parameters were determined using both compartmental and non
      compartmental analyses. The calculated clearance (CL) following IV administration
      was 7.19 +/- 0.83 ml/kg/min, and the estimated volume of distribution at steady
      state (V ss) was 700.90 +/- 55.01 ml/kg. Whereas with PO dosing, apparent CL/F
      value was 12.30 +/- 0.30 ml/min/kg and V ss/F was 5,109.46 +/- 196.08 ml/kg.
      These parameters were associated with an elimination half-life (T 1/2) of 63.43
      +/- 10.69 and 274.61 +/- 8.48 min with IV and PO dosing, respectively. The
      calculated absorption T 1/2 was about 217 min. Compartmental analysis revealed T
      1/2alpha of ~8.9 min and T 1/2beta of ~86.6 min. The calculated absolute
      bioavailability of THQ was ~58 % with a lag time of ~23 min. The estimated THQ
      protein binding was >99 %. Therefore, THQ represents a compound with rapid
      elimination and relatively slower absorption following PO administration.

PMID- 24924309
TI  - Cell division and targeted cell cycle arrest opens and stabilizes basement
      membrane gaps.
AB  - Large gaps in basement membrane (BM) occur during organ remodelling and cancer
      cell invasion. Whether dividing cells, which temporarily reduce their attachment
      to BM, influence these breaches is unknown. Here we analyse uterine-vulval
      attachment during development across 21 species of rhabditid nematodes and find
      that the BM gap that forms between these organs is always bounded by a non
      dividing vulval cell. Through cell cycle manipulation and live cell imaging in
      Caenorhabditis elegans, we show that actively dividing vulval cells facilitate
      enlargement of this breach by promoting BM movement. In contrast, targeted cell
      cycle arrest halts BM movement and limits gap opening. Further, we demonstrate
      that the BM component laminin accumulates at the BM gap edge and promotes
      increased integrin levels in non-dividing vulval cells, stabilizing gap position.
      Together, these studies reveal that cell division can be used as a mechanism to
      regulate BM breaches, thus controlling the exchange of cells between tissues. 

PMID- 24924311
TI  - Comparison of the pharmacokinetics of linezolid in burn and non-burn rabbits.
AB  - Linezolid is effective on many resistant organisms for the treatment of severe
      infections in burns. However, its pharmacokinetics was difficult to predict after
      major burns. The study aimed to describe the pharmacokinetic properties of
      linezolid administered intravenously at a dose of 10 mg/kg in severely burned
      rabbits in comparison to that in non-burns. Linezolid concentrations were
      quantitatively analyzed by high-performance liquid chromatography. The direct
      consequence of the physiological changes after burn injury was lower plasma
      linezolid concentrations. In addition, burn injury induced significantly altered
      pharmacokinetic parameters with higher inter-individual variability. The
      distribution volume and clearance rate were increased (2.88 vs. 1.92 L/kg, P >
      0.05; 0.28 vs. 0.20 L/h/kg, P < 0.05), and the AUC0-infinity was significantly
      lower (37.99 vs. 51.47 mg/L h, P < 0.05). However, there were almost no changes
      in half-life and mean residence time. These results suggested that therapeutic
      drug monitoring and dosage individualization of linezolid in patients with severe
      burns were necessary.

PMID- 24924313
TI  - Occupational injury risk by sex in a manufacturing cohort.
AB  - OBJECTIVES: This study expands previous research comparing injury risk for women
      and men in a cohort of 24,000 US aluminium manufacturing workers in 15 facilities
      from 2001 to 2010. METHODS: We compared injury rates (all injury, first aid,
      medical treatment, restricted work and lost work time) by sex and by job and sex.
      Using a mixed effect modelling approach, we calculated ORs and 95% CIs adjusting
      for age, job tenure, ethnicity and year as fixed effects and person, job and
      plant as random effects. Additionally, we modelled the data stratified by plant
      type to examine potential differences in injury risk between smelter (generally
      recognised as more hazardous) and fabrication production environments. RESULTS:
      Risk of injury was higher for women in four out of the five injury outcomes: all
      injuries combined (OR: 1.58, CI 1.48 to 1.67), injuries requiring first aid (OR:
      1.61, CI 1.54 to 1.70), injuries requiring medical treatment (OR: 1.18, CI 1.03
      to 1.36) and injuries requiring restricted work (OR: 1.65, CI 1.46 to 1.87). No
      difference in the risk of lost time injury by sex was found in this cohort.
      Analyses stratified by plant type showed similarly elevated injury risk for
      women, although the risk estimates were higher in smelters than fabrication
      plants. CONCLUSIONS: To our knowledge, this is the largest single-firm study
      examining injury risk by sex with sufficient data to appropriately adjust for
      job. We show a consistently higher injury risk for women compared with men in the
      smelting and fabrication environments.

PMID- 24924312
TI  - Benzylideneacetophenone derivatives attenuate IFN-gamma-induced IP-10/CXCL10
      production in orbital fibroblasts of patients with thyroid-associated
      ophthalmopathy through STAT-1 inhibition.
AB  - The aim of the present study was to identify a new candidate anti-inflammatory
      compound for use in the active stage of thyroid-associated ophthalmopathy (TAO).
      Benzylideneacetophenone compound JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro
      2-en-l-one] was synthesized based on a structural modification of yakuchinone B,
      a constituent of the seeds of Alpinia oxyphylla, which belongs to the ginger
      family (Zingiberaceae), has been widely used in folk medicine as an anti
      inflammatory phytochemical. Orbital fibroblasts were primarily cultured from
      patients with TAO, and the potential of JC3 to suppress the interferon (IFN)
      gamma-induced protein (IP)-10/CXCL10 production in these cells was determined.
      IFN-gamma strongly increased the level of IP-10/CXCL10 in orbital fibroblasts
      from patients with TAO. JC3 exerted a significant inhibitory effect on the IFN
      gamma-induced increase in IP-10/CXCL10 in a dose-dependent manner; its potency
      was greater than that of an identical concentration of yakuchinone B with no
      toxicity to cells at the concentration range used. Moreover, the constructed
      dimer and trimer polystructures of JC3, showed greater potency than JC3 in
      suppressing the IFN-gamma-induced production of IP-10/CXCL10. JC3 significantly
      attenuated the IP-10/CXCL10 mRNA expression induced by IFN-gamma, and a gel-shift
      assay showed that JC3 suppressed IFN-gamma-induced DNA binding of signal
      transducer and activator of transcription-1 (STAT-1) in TAO orbital fibroblasts.
      Our results provide initial evidence that the JC3 compound reduces the levels of
      IP-10/CXCL10 protein and mRNA induced by IFN-gamma in orbital fibroblasts of TAO
      patients. Therefore, JC3 might be considered as a future candidate for
      therapeutic application in TAO that exerts its effects by modulating the
      pathogenic mechanisms in orbital fibroblasts. 

PMID- 24924314
TI  - Phase 1 clinical trial of VesicareTM (solifenacin) in the treatment of urinary
      incontinence after radical prostatectomy.
AB  - PURPOSE: Permanent and prolonged incontinence following robot assisted radical
      prostatectomy (RARP) is known to result from injury to the external sphincter. We
      hypothesize that pre-existing detrusor overactivity may also contribute to
      delayed return of continence (>3 months). This pilot study examines the safety
      profile and efficacy of muscarinic receptor antagonist, solifenacin, in
      incontinent men after prostatectomy. MATERIALS AND METHODS: Men using three or
      more pads 7 days post catheter removal were invited to enroll into the study (5
      mg daily of solifenacin for 3 months). All subjects received RARP under
      hypothermic conditions by one surgeon. Continence was defined as 0 pads. RESULTS:
      Forty men were enrolled, one excluded due to missing follow-up. Two men reported
      nonserious adverse events: one a vaso-vagal reaction when taking solifenacin with
      sildenafil, and the other was dehydration and dizziness after strenuous exercise.
      Additionally, four withdrew due to side effects. The efficacy outcomes show
      improved intermittency after prostatectomy, though unclear if due to the
      medication. At 3 months, 21 patients (53.8%) reached the primary continence
      outcome of zero pads. The median time to continence in this group was 95 days.
      CONCLUSIONS: Solifenacin is well tolerated in post radical prostatectomy patients
      with a 15% withdrawal rate due to side effects. These results formed the basis of
      a large, prospectively randomized clinical trial comparing the effects of
      solifenacin versus placebo in a population of men incontinent after RARP.

PMID- 24924315
TI  - Chloride-assisted catalytic water oxidation.
AB  - Rates of electrocatalytic water oxidation to oxygen by Ru(II) polypyridyl
      complexes are enhanced by added NaCl. Observations based on the single-site
      catalyst [Ru(II)(Mebimpy)(bpy)(OH2)](2+) (Mebimpy is 2,6-bis(1-methylbenzimidazol
      2-yl)pyridine; bpy is 2,2'-bipyridine) at pH 7.0 in a phosphate buffer suggest a
      mechanism involving initial oxidation of the catalyst to Ru(V)(O)(3+) followed by
      Cl(-) oxidation to HOCl. Once formed, HOCl is oxidized to O2.

PMID- 24924317
TI  - Someone does believe the introductory books: Mahoney's problems with behaviorism.

PMID- 24924316
TI  - Comparison between two types of improved motion-sensitized driven-equilibrium
      (iMSDE) for intracranial black-blood imaging at 3.0 tesla.
AB  - PURPOSE: To investigate the image quality impact of a new implementation of the
      improved motion-sensitized driven-equilibrium (iMSDE) pulse scheme in the human
      brain at 3.0 Tesla. MATERIALS AND METHODS: Two iMSDE preparation schemes were
      compared; (a) iMSDE-1: two refocusing pulses and two pairs of bipolar gradients
      and (b) iMSDE-2: adding extra bipolar gradients in front of the iMSDE-1
      preparation. Computer simulation was used to evaluate the difference of eddy
      currents effect between these two approaches. Five healthy volunteers were then
      scanned with both sequences in the intracranial region and signal changes
      associated with iMSDE-1 and iMSDE-2 were assessed and compared quantitatively and
      qualitatively. RESULTS: Simulation results demonstrated that eddy currents are
      better compensated in iMSDE-2 than in the iMSDE-1 design. In vivo comparison
      showed that the iMSDE-2 sequence significantly reduced the tissue signal loss at
      all locations compared with iMSDE-1 (5.0% versus 23% in average, P < 0.0002 at
      paired t-test). The signal in iMSDE-1 showed greater spatial inhomogeneity than
      that of iMSDE-2. CONCLUSION: Our results show that iMSDE-2 demonstrated smaller
      loss in signal and less spatial variation compared with iMSDE-1, we conjecture
      due to the improved eddy current compensation.

PMID- 24924318
TI  - Matching by horses on several concurrent variable-interval schedules.
AB  - Using three horses we imvestigated responding on several concurrent variable
      interval schedules. Each horse was first trained, using the method of successive
      approximations, to press a response lever with its upper lip. Following
      successful acquisition of the lip-press response, horses spent several days on
      pretraining schedules. These included a continuous reinforcement schedule and
      three variable-interval concurrent schedules: VI 15-sec VI 15-sec, VI 30-sec VI
      30-sec, and VI 45-sec VI 45-sec. Horses were then exposed to the experimental
      sessions; sessions were conducted daily in the horse's home stall and lasted
      until 60 grain reinforcers had been received. All horses were exposed to five
      variable-interval schedules: VI 30-sec VI 90-sec, VI 45-sec VI 75-sec, VI 60-sec
      VI 60-sec, VI 75-sec VI 45-sec, and VI 90-sec VI 30-sec. Like previous
      experimenters, we found a close matching relationship between the horse's
      relative rates of responding and the relative rates of reinforcement. When each
      horse's data was fitted with a regression line, using the least squares method,
      more than 97% of the variance was accounted for. These results expand the
      generality of the matching law to include horses as well as providing some other
      information about the response characteristics of horses. 

PMID- 24924319
TI  - Ambiguous stimuli and delayed matching to sample.
AB  - Four pigeons learned a delayed matching task in which the sample and choice
      stimuli were line orientations. After performance had reached a high level of
      accuracy the procedure was altered so that only one of the line choice stimuli
      was presented on each trial and a uniform white field was presented on the other
      key. In the first experiment the position of the white key alternated between
      left and right in successive sessions. Three of the four subjects suffered no
      loss in accuracy when the white key was on one side but responded only slightly
      better than chance when it was on the other. A second experiment showed that this
      position effect was not eliminated by keeping the white key in the same position
      for a number of sessions and, for three of the four subjects, was not affected by
      changing the color from white to red. 

PMID- 24924320
TI  - Agonistic interactions and exploitation of limited food sources in Blattella
      germanica (L.).
AB  - The importance of size asymmetries between contestants that engage in agonistic
      interactions at a limited food source were investigated. Rates of agonistic
      interactions at the experimental food sources were not density-dependent. Most of
      the interactions concerned dyads either of the same developmental stage or of
      close developmental stages. Larvae interacted more frequently with an animal of
      the same developmental stage whereas adults interacted more frequently with an
      adult of the other sex or with a large, instar 6, larva. According to the
      composition of the feeding group, the number of acts initiated per individual per
      unit time varied with developmental stage. A factorial analysis of
      correspondence, followed by a cluster analysis, enabled us to define three
      categories of interacting groups according to group structure. Feeding group
      structure influenced the level of individual aggression, particularly in adults.
      We show how a slight change in group structure modified intensity and direction
      of aggressiveness, particularly in males and in females. 

PMID- 24924321
TI  - Early maternal discrimination of alien kids by post-parturient goats.
AB  - Dwarf Creole goats (n = 6) and mixed blood goats of dairy breeds (n = 13) were
      tested for their ability to show selective care for their kids after post-partum
      mother-young contact ranging from 2.5 to 12 h (mean: 5.0 h). 18 out of 19 mothers
      were found to be selective and to reject alien young presented to them. Rejection
      was independent of the age of the alien (range: 3 to 28 h; mean 9.3 h) and of
      duration of mother-young contact prior to the test. Last we found that only one
      mother of multiple young (n = 13) showed signs of recognition of litter size. Our
      results indicate that goat mothers can establish a selective bond as rapidly as
      sheep, and that they reject alien kids younger than the time necessary for the
      development of labelling as reported previously. Additional mechanisms may also
      be involved in the establishment of early maternal selectivity in goats. 

PMID- 24924322
TI  - Time allocations of various activities under multiple schedules in pigeons.
AB  - Time allocations of three pigeons' various activities (pecking, turning,
      preening, wing flapping, etc.) were measured under usual multiple schedules in
      which only key-peck response was reinforced. Positive behavioral contrast was
      found for both the number and the time allocation of key-peck response. Some time
      allocations of the other activities were inversely varied to that of key-pecks,
      as stated in the competition theory of behavioral contrast. However, the amount
      of reallocation of interim activities was not enough to complement the amount of
      increases or decreases of key-pecks in the unchanged component. Most of the
      amount of increases or decreases of key-pecks in the unchanged component was
      complemented with the inactive time. This result suggests that behavioral
      competition is not the primary mechanism for key-peck behavioral contrast in
      multiple schedules in pigeons. It is important to consider inactive time, which
      is emerged in the usual experimental setting, to clearly attribute the behavioral
      contrast to reallocation of time for other activities. 

PMID- 24924323
TI  - Preferences for constant duration delays and constant sized rewards in human
      subjects.
AB  - In four experiments, human subjects played a simple video game in which they
      chose between two buttons that provided reinforcement either on constant or
      variable schedules. In one condition of Experiment 1, subjects strongly preferred
      constant sized rewards over variable sized rewards. In the two other conditions,
      subjects preferred constant duration delays-to-reinforcement over variable
      duration delays-to-reinforcement. In Experiment 2, subjects were exposed to
      different parameters and, in Experiment 3, they were exposed to a modified
      temporal procedure. In each case, subjects continued to prefer constant sized
      rewards and constant duration delays. The preference for constant duration delays
      contradicts analogous research showing that pigeons and rats prefer variable
      duration delays over constant duration delays. In Experiment 4, we explored this
      difference by omitting the prompts that segmented the phases of the procedure.
      Under these conditions, the subjects preferred the variable duration delays.
      Based on these results, we argue that in the absence of effective signals, both
      people and animals may be forced to use secondary choice strategies such as a
      proportional waiting rule. The presence of prompts, however, enables people to
      segment the choice phase and directly choose between the fixed and variable
      duration delays. 

PMID- 24924324
TI  - Choice in a self-control paradigm: effects of uncertainty.
AB  - Four experiments examined humans' self-control and impulsiveness as a function of
      reinforcer uncertainty. Uncertainty was manipulated by varying the probability
      and durations of interruptions, temporary periods of timeout from reinforcement.
      In Experiment 1 the probability of an interruption varied while its duration was
      constant. In Experiment 2 the duration of an interruption varied while its
      probability was constant. In Experiment 3, the subjects were interrupted only
      during the delay to the larger, more delayed reinforcer. In Experiment 4 the
      subjects experienced the same amounts and delays of reinforcement as in
      Experiments 1-3, but did not experience any interruptions. The subjects in
      Experiments 1 and 2 were not significantly more impulsive than the subjects in
      Experiment 4. In Experiment 3, the subjects exhibited significantly more
      impulsiveness than the subjects in Experiments 1, 2 and 4 when the reinforcement
      rates were equal, but not when they were unequal. Reinforcer uncertainty affects
      choice behavior to the extent that it influences the relative reinforcement rate.

PMID- 24924325
TI  - Seasonal movements of female Corsican mouflon (Ovis ammon) in a Mediterranean
      mountain range, southern France.
AB  - The spatial occupation of female Corsican mouflon (Ovis ammon) in medium
      Mediterranean mountains of southern France, was studied between the end of 1987
      and June 1989. It can be divided into two seasonal home ranges, one in
      fall/winter, and one in spring/summer. Both seasonal home ranges start with a
      period of intense locomotive activity in the different individuals. This
      behaviour could be explained by a general inclination of the animals to move on
      large scale, the expression of this inclination being allowed by the favourable
      environmental conditions in spring and fall. In any case, the comparison of our
      results with those obtained from mountain populations of the genus Ovis, suggests
      that 'phylogenetic inertia' exists towards certain modalities in spatial
      occupation. Indeed, the observed seasonal movements do not seem to retain a real
      adaptive character in our Mediterranean study area, as shown by the overlap of
      ranges, the use of the same type of habitat during the seasons and the great
      variability between individuals. 

PMID- 24924326
TI  - Factors affecting the incidence of dawn calling in red-legged and grey
      partridges.
AB  - Seasonal variations in the frequency and the timing of calling in red-legged
      (Alectoris rufa) and grey (Perdix perdix) partridges, and their relationships
      with biological and environmental factors, were investigated during 89 morning
      surveys. In winter, when birds were living in social groups, the vocal activity
      of both species decreased. Most calling began before sunrise. Yet many variations
      in the timing of first calls were observed when sunrise was prior to 0530 h, i.e.
      when the daylength was above 13 hours. On the contrary, when daylength was
      shorter, calling activity always began approximately 45 minutes before sunrise.
      Red-legged partridge calls were more particularly stimulated when sunrise was
      between 0530 h and 0700 h, with no wind, when moonrise was between 0000 h and
      0900 h, and when cloud cover was low. 

PMID- 24924327
TI  - Dustbathing as related to proximal and distal feather lipids in laying hens.
AB  - After a prolonged experience with wood-shavings or with sand, 2 x 11 hens (Gallus
      gallus domesticus) were litter-deprived. Prior to the 7 to 8 day deprivation
      period feather samples were taken. This was repeated immediately after the
      deprivation had ended and right after the first bath in the familiar litter. Each
      feather was cut at the transition between the proximal plumulous and distal
      pennaceous part and lipids were extracted from separate samples, containing one
      type of feather parts. Hens on wood-shavings bathed 10 minutes longer after
      deprivation than hens on sand. This was due only to an extension of the second
      phase of the dustbath, which included rubbing; the first phase of tossing did not
      differ. In the extended phase of the wood-shavings bath the tendency to rub was
      lower, whereas the tendency to toss was higher than in the comparable phase of
      the sand bath. Thus, litter quality affected the amount of rubbings and of
      tossings in between. Rubbing did not effectuate a close contact between wood
      shavings and the proximal integument, as wood-shavings could not be tossed into
      the plumage. This contrasted with baths in sand and only these baths resulted in
      a removal of excessive lipids from the plumulous parts. Therefore rubbing seems
      functionally crucial. The lipid level immediately after deprivation and the
      change in the quantity of lipids due to deprivation positively correlated with
      the amount of tossings in wood-shavings and with the amount of rubbings in sand.
      This indicates that the lipid condition is causally involved in dustbathing. 

PMID- 24924328
TI  - Responses of adult domestic cocks and capons to novel and alarming stimuli.
AB  - The present study compared the responses of adult domestic cocks and capons to a
      variety of novel and potentially frightening events. Cocks took longer to feed,
      spent less time feeding and ate less of their diet when it was dyed an unfamiliar
      colour than did capons. They also showed more pronounced avoidance of a novel
      object placed in the food trough. Conversely, cocks showed less behavioural
      inhibition than capons when placed individually in an unfamiliar pen (open field)
      containing a human observer: they ambulated sooner and more, and vocalized,
      pecked at the environment and flapped their wings more often. No significant
      differences were found between the tonic immobility fear reactions of cocks and
      capons. The pattern of results is considered more likely to reflect the
      stabilisation of attention by testosterone rather than any direct effect of the
      hormone on the ease of evocation and expression of fear. 

PMID- 24924329
TI  - Increased distractability in capons: an adult parallel to androgen-induced
      effects in the domestic chick.
AB  - In the male domestic chick, one consequence of the stabilisation of attention by
      testosterone is an increased ability to pass conspicuous novel features
      introduced within a runway, in order to continue and reach food. Cocks are here
      shown to be better able to do this than capons. When faced with such conspicuous
      change (coloured panels suspended on the runway walls, coloured tapes attached to
      the food dish), capons instead began to search for food elsewhere within the
      runway, and to show other signs of shifting attention, such as looking up in
      preparation for leaving the runway. Capons receiving testosterone therapy behaved
      more like cocks. It is thus likely that testicular androgens stabilise attention
      in adult cocks. Since the corresponding effect in young chicks has short latency,
      (unlike classic effects of testosterone on attack and copulation), the same may
      be true in adults. Facilitation of attack and stabilisation of attention, as
      separate effects of testosterone, may interact to bring about greater confidence
      in dominant adult cocks with elevated levels of testosterone. 

PMID- 24924330
TI  - Fish movement behaviour: variability within and between groups.
AB  - The movement behaviour of mullet, Mugil cephalus (Linnaeus), an obligate
      schooling fish species, was recorded for individuals in small groups. Mean speeds
      and mean turning frequencies both declined significantly with increasing group
      size. Significant differences between groups were attributed to individual
      variation. However, within groups the movements of individuals were highly
      coordinated. As the size of fish schools increases, behavioural convergence
      mediated by the monitoring of companions rapidly masks individual variation and
      leads to the characteristic uniformity of such aggregations. 

PMID- 24924331
TI  - Depressive symptomatology in men receiving androgen deprivation therapy for
      prostate cancer: a controlled comparison.
AB  - OBJECTIVE: Prostate cancer patients who receive androgen deprivation therapy
      (ADT) often experience many physical and psychological side effects. ADT may be
      associated with increased risk for depression, but the relationship between ADT
      and depression is not fully understood. This study used a longitudinal design to
      assess depressive symptomatology in patients receiving ADT compared with two
      groups of matched controls. METHODS: Participants were men initiating ADT
      treatment (ADT+ group; n = 61) and their matched controls: prostate cancer
      patients treated with radical prostatectomy (ADT- group; n = 61), and no-cancer
      controls (CA- group; n = 61). Depressive symptomatology was assessed using the
      Center for Epidemiological Studies Depression Scale at ADT initiation and again 6
      months later. Differences in depressive symptomatology and rates of clinically
      significant depressive symptomatology were analyzed between groups at each time
      point and within groups over time. RESULTS: Between baseline and follow-up, ADT+
      participants demonstrated increased depressive symptomatology and increased rates
      of clinically significant depressive symptomatology (ps < 0.05). ADT+
      participants also reported greater depressive symptomatology than both control
      groups at follow-up (ps < 0.001). Rates of clinically significant depressive
      symptomatology were higher in the ADT+ group than the ADT- and CA- groups at both
      time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%). CONCLUSIONS:
      Findings support the hypothesis that ADT administration yields increases in
      depression and suggest that the mechanism behind ADT's association with
      depression should be explored and that prostate cancer patients treated with ADT
      should receive particular focus in depression screening and intervention.

PMID- 24924332
TI  - Pattern of mutation rates in the germline of Drosophila melanogaster males from a
      large-scale mutation screening experiment.
AB  - The sperm or eggs of sexual organisms go through a series of cell divisions from
      the fertilized egg; mutations can occur at each division. Mutations in the
      lineage of cells leading to the sperm or eggs are of particular importance
      because many such mutations may be shared by somatic tissues and also may be
      inherited, thus having a lasting consequence. For decades, little has been known
      about the pattern of the mutation rates along the germline development. Recently
      it was shown from a small portion of data that resulted from a large-scale
      mutation screening experiment that the rates of recessive lethal or nearly lethal
      mutations differ dramatically during the germline development of Drosophila
      melanogaster males. In this paper the full data set from the experiment and its
      analysis are reported by taking advantage of a recent methodologic advance. By
      analyzing the mutation patterns with different levels of recessive lethality,
      earlier published conclusions based on partial data are found to remain valid.
      Furthermore, it is found that for most nearly lethal mutations, the mutation rate
      at the first cell division is even greater than previous thought compared with
      those at other divisions. There is also some evidence that the mutation rate at
      the second division decreases rapidly but is still appreciably greater than those
      for the rest of the cleavage stage. The mutation rate at spermatogenesis is
      greater than late cleavage and stem-cell stages, but there is no evidence that
      rates are different among the five cell divisions of the spermatogenesis. We also
      found that a modestly biased sampling, leading to slightly more primordial germ
      cells after the eighth division than those reported in the literature, provides
      the best fit to the data. These findings provide conceptual and numerical basis
      for exploring the consequences of differential mutation rates during individual
      development. 

PMID- 24924333
TI  - UV fluorescence of tryptophan residues effectively measures protein binding to
      nucleic acid fragments immobilized in gel elements of microarrays.
AB  - Microarrays allow for the simultaneous monitoring of protein interactions with
      different nucleic acid (NA) sequences immobilized in microarray elements. Either
      fluorescently labeled proteins or specific fluorescently labeled antibodies are
      used to study protein-NA complexes. We suggest that protein-NA interactions on
      microarrays can be analyzed by ultraviolet (UV) fluorescence of tryptophan
      residues in the studied proteins, and this approach may eliminate the protein
      labeling step. A specialized UV microscope was developed to obtain fluorescent
      images of microarrays in the UV wavelengths and to measure the fluorescence
      intensity of individual microarray elements. UV fluorescence intensity of BSA
      immobilized in microarray gel elements increased linearly with increased BSA
      amount with sensitivity of 0.6 ng. Real-time interaction curves between the DNA
      binding domain of the NFATc1 transcription factor (NFATc1-DBD) and synthetic
      hairpin-forming oligodeoxyribonucleotides immobilized within 0.2 nL microarray
      gel elements at a concentration 5 * 10(-5) M and higher were obtained. The UV
      fluorescence intensities of microarray gel elements containing NFATc1-DBD-DNA
      complexes at equilibrium allowed the estimation of the equilibrium binding
      constant for complex formation. The developed method allows the protein-NA
      binding to be monitored in real time and can be applied to assess the sequence
      specific affinity of NA-binding proteins in parallel studies involving many NA
      sequences. 

PMID- 24924334
TI  - Apparent diffusion coefficient measurements as very early predictive markers of
      response to chemotherapy in hepatic metastasis: a preliminary investigation of
      reproducibility and diagnostic value.
AB  - PURPOSE: To evaluate the reproducibility and diagnostic value of apparent
      diffusion coefficient (ADC) as an early predictor of response to chemotherapy of
      liver metastasis in routine clinical practice. MATERIALS AND METHODS: A
      prospective study of 20 patients with histologically proven primary tumors with
      liver metastases was undertaken. Diffusion weighted MRI was performed twice
      before and 12-14 days after the start of treatment. Absolute and liver normalized
      ADC values were calculated. Bland Altman statistics were used to assess the
      reproducibility of ADC change for predicting lesion response as measured by
      RECIST. RESULTS: Nineteen of 31 metastases responded. Significant increases in
      absolute and normalized ADC values were found in responding (mean +208.7 * 10(-6)
      m(2)/s and +18% respectively, both P < 0.001) compared with nonresponding lesions
      (mean +98.6 * 10(-6) m(2)/s and 2%, respectively, P = 0.09 and 0.519).
      Reproducibility was better using normalized ADC compared with absolute ADC values
      (within patient coefficient of variability 8.0% and 10.1%, respectively). Using
      the repeatability threshold of +/-22.3% for normalized ADC, only 8 of 19
      responding and all but one nonresponding lesions could be prospectively detected.
      CONCLUSION: Increases in ADC values in responding liver metastases occurred
      within days after the start of chemotherapy but were of smaller magnitude than
      the variability of ADC measurement. These preliminary data suggest that the
      presently used technique is not reliable enough to predict final response at such
      an early time point in individual lesions.

PMID- 24924336
TI  - Not just neuroanesthesia, but Pediatric neuroanesthesia!

PMID- 24924335
TI  - Podocytes degrade endocytosed albumin primarily in lysosomes.
AB  - Albuminuria is a strong, independent predictor of chronic kidney disease
      progression. We hypothesize that podocyte processing of albumin via the lysosome
      may be an important determinant of podocyte injury and loss. A human urine
      derived podocyte-like epithelial cell (HUPEC) line was used for in vitro
      experiments. Albumin uptake was quantified by Western blot after loading HUPECs
      with fluorescein-labeled (FITC) albumin. Co-localization of albumin with
      lysosomes was determined by confocal microscopy. Albumin degradation was measured
      by quantifying FITC-albumin abundance in HUPEC lysates by Western blot.
      Degradation experiments were repeated using HUPECs treated with chloroquine, a
      lysosome inhibitor, or MG-132, a proteasome inhibitor. Lysosome activity was
      measured by fluorescence recovery after photo bleaching (FRAP). Cytokine
      production was measured by ELISA. Cell death was determined by trypan blue
      staining. In vivo, staining with lysosome-associated membrane protein-1 (LAMP-1)
      was performed on tissue from a Denys-Drash trangenic mouse model of nephrotic
      syndrome. HUPECs endocytosed albumin, which co-localized with lysosomes.
      Choloroquine, but not MG-132, inhibited albumin degradation, indicating that
      degradation occurs in lysosomes. Cathepsin B activity, measured by FRAP,
      significantly decreased in HUPECs exposed to albumin (12.5% of activity in
      controls) and chloroquine (12.8%), and declined further with exposure to albumin
      plus chloroquine (8.2%, p<0.05). Cytokine production and cell death were
      significantly increased in HUPECs exposed to albumin and chloroquine alone, and
      these effects were potentiated by exposure to albumin plus chloroquine. Compared
      to wild-type mice, glomerular staining of LAMP-1 was significantly increased in
      Denys-Drash mice and appeared to be most prominent in podocytes. These data
      suggest lysosomes are involved in the processing of endocytosed albumin in
      podocytes, and lysosomal dysfunction may contribute to podocyte injury and
      glomerulosclerosis in albuminuric diseases. Modifiers of lysosomal activity may
      have therapeutic potential in slowing the progression of glomerulosclerosis by
      enhancing the ability of podocytes to process and degrade albumin. 

PMID- 24924337
TI  - Cerebral perfusion pressure: how low can we go?

PMID- 24924338
TI  - Designing a safe and sustainable pediatric neurosurgical practice: the English
      experience.
AB  - The 2001 Report of the Public Inquiry into children's heart surgery at the
      Bristol Royal Infirmary 1984-1995 stated that there must be standards for
      hospitals as a whole and that hospitals, which do not meet these standards,
      should not be able to offer services within the National Health Service (NHS). In
      2013, agreed standards for pediatric neurosurgery were produced. Between 2001 and
      2013 several key documents were published, which formed the background to the
      review that produced these standards:, the 'Safe and Sustainable' review. The
      process had the mission statement, 'Safe, sustainable and world class. Not
      ordinary, OK or just good enough.' In April 2013, the new commissioning structure
      of NHS England came into being. Clinical Reference Groups (reporting directly
      into the new structure) and pediatric neurosurgical operational delivery networks
      are taking the Safe and Sustainable pediatric neurosurgery standards and models
      of care into practice in England. Effective outcome data collection will allow us
      to assess whether these networks will improve equity of access for English
      children to world-class pediatric neurosurgical care and reduce the variation in
      outcomes seen at the present time. 

PMID- 24924339
TI  - The postoperative management of pain from intracranial surgery in pediatric
      neurosurgical patients.
AB  - Pain following intracranial surgery has historically been undertreated because of
      the concern that opioids, the analgesics most commonly used to treat moderate-to
      severe pain, will interfere with the neurologic examination and adversely affect
      postoperative outcome. Over the past decade, accumulating evidence, primarily in
      adult patients, has revealed that moderate-to-severe pain is common in
      neurosurgical patients following surgery. Using the neurophysiology of pain as a
      blueprint, we have highlighted some of the drugs and drug families used in
      multimodal pain management. This analgesic method minimizes opioid-induced
      adverse side effects by maximizing pain control with smaller doses of opioids
      supplemented with neural blockade and nonopioid analgesics, such nonsteroidal
      antiinflammatory drugs, local anesthetics, corticosteroids, N-methyl-D-aspartate
      (NMDA) antagonists, alpha2 -adrenergic agonists, and/or anticonvulsants
      (gabapentin and pregabalin). 

PMID- 24924340
TI  - Use of tranexamic acid in infants undergoing choroid plexus papilloma surgery: a
      report of two cases.
AB  - Choroid plexus papilloma (CPP) is a highly vascular tumor of infancy. Reducing
      blood loss is the key to successful surgical removal of CPPs. Tranexamic acid
      (TXA) is efficacious in reducing bleeding in craniofacial surgery for infants.
      This report demonstrates the potential utility of TXA for decreasing blood loss
      in the removal of vascular tumors in infants. We administered tranexamic acid to
      two infants with CPP during surgical removal to potentially aid hemostasis and
      therefore lessen intra-operative bleeding. Gross total surgical resection was
      accomplished; the patients were hemodynamically stable perioperatively, and the
      total calculated blood loss was minimal at <20% of the patients' total
      circulating blood volume. This is the first report of tranexamic acid
      administration for CPP surgery in children. TXA is an easily administered
      hemostatic agent and may merit further study as an agent to help reduce intra
      operative blood loss in this vulnerable population. 

PMID- 24924341
TI  - [Oxytocin for the prophylaxis of uterine atony after cesarean delivery. Should we
      reconsider our protocols?].

PMID- 24924342
TI  - [Reply to article "Iliac aneurysm rupture during preconditioning with
      levosimendan for coronary artery graft, it was levosimendan the most influencing
      factor?"].

PMID- 24924343
TI  - Use of platelet-rich fibrin as an autologous biologic rejuvenating media for
      avulsed teeth - an in vitro study.
AB  - AIM: The prognosis of replanted avulsed tooth depends on the existence of viable
      cells in the periodontal ligament and also on those cells which are able to
      proliferate on the damaged areas of the root. The purpose of this study was to
      evaluate the survival of periodontal ligament cells (PDL) when soaked in an
      autologous biologic rejuvenating media after an extra-oral dry time of 40 min.
      METHOD: Thirty teeth were selected with intact crown which were advised for
      Orthodontic extraction having healthy PDL. They were divided into two
      experimental and two control groups. The positive and negative controls
      corresponded to 0-min and 1-h dry time, respectively. The experimental teeth were
      stored dry for 40 min and then immersed in one of the two media, combination of
      platelet-rich fibrin and platelet poor plasma (PRF+PPP) and PPP for 45 min. The
      teeth in each group were treated with dispase II and collagenase for 30 min and
      later centrifuged for 5 min at 50.17 g. The supernatant was removed with sterile
      micropipette, the cells labelled with 0.4% trypan blue, and the number of viable
      PDL cells was counted with a haemocytometer, under a light microscope. RESULTS:
      anova and Mann-Whitney U-test demonstrated statistically significant differences
      in the viability of PDL cells among experimental groups. CONCLUSION: Within the
      parameters of this study, a combination of platelet-rich fibrin and PPP
      demonstrated higher number of viable PDL cells and hence could be a good biologic
      rejuvenating media for avulsed teeth.

PMID- 24924344
TI  - Application of next generation sequencing to CEPH cell lines to discover variants
      associated with FDA approved chemotherapeutics.
AB  - BACKGROUND: The goal of this study was to perform candidate gene association with
      cytotoxicity of chemotherapeutics in cell line models through resequencing and
      discovery of rare and low frequency variants along with common variations. Here,
      an association study of cytotoxicity response to 30 FDA approved drugs was
      conducted and we applied next generation targeted sequencing technology to
      discover variants from 103 candidate genes in 95 lymphoblastoid cell lines from
      14 CEPH pedigrees. In this article, we called variants across 95 cell lines and
      performed association analysis for cytotoxic response using the Family Based
      Association Testing method and software. RESULTS: We called 2281 variable SNP
      genotypes across the 103 genes for these cell lines and identified three genes of
      significant association within this marker set. Specifically, ATP-binding
      cassette, sub-family C, member 5 (ABCC5), metallothionein 1A (MT1A) and NAD(P)H
      dehydrogenase quinone1 (NQO1) were significantly associated with oxaliplatin drug
      response. The significant SNP on NQO1 (rs1800566) has been linked with poor
      survival rates in patients with non-small cell lung cancer treated with cisplatin
      (which belongs to the same class of drugs as oxaliplatin). A SNP (rs1846692) near
      the 5' region of MT1A was associated with arsenic trioxide. CONCLUSIONS: The
      results from this study are promising and this serves as a proof-of-principle
      demonstration of the use of sequencing data in the cytotoxicity models of human
      cell lines. With increased sample sizes, such studies will be a fast and powerful
      way to associate common and rare variants with drug response; while overcoming
      the cost and time limitations to recruit cohorts for association study.

PMID- 24924345
TI  - Meta-analysis of melanin-concentrating hormone signaling-deficient mice on
      behavioral and metabolic phenotypes.
AB  - The demand for meta-analyses in basic biomedical research has been increasing
      because the phenotyping of genetically modified mice does not always produce
      consistent results. Melanin-concentrating hormone (MCH) has been reported to be
      involved in a variety of behaviors that include feeding, body-weight regulation,
      anxiety, sleep, and reward behavior. However, the reported behavioral and
      metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient
      mice and MCH receptor 1 (MCHR1)-deficient mice, are not consistent with each
      other. In the present study, we performed a meta-analysis of the published data
      related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions
      about the role of MCH signaling. Overall, the meta-analysis revealed that the
      deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression,
      and male sexual behavior and that MCH signaling deficiency suppressed non-REM
      sleep, anxiety, responses to novelty, startle responses, and conditioned place
      preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling
      deficiency significantly increased food intake. Overall, the meta-analysis also
      revealed that the deletion of MCH signaling suppressed the body weight, fat mass,
      and plasma leptin, while MCH signaling deficiency increased the body temperature,
      oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of
      the MCH signaling-deficient mice was also confirmed in separate meta-analyses
      that were specific to sex and background strain (i.e., C57BL/6 and 129Sv). MCH
      signaling deficiency caused a weak anxiolytic effect as assessed with the
      elevated plus maze and the open field test but also caused a weak anxiogenic
      effect as assessed with the emergence test. MCH signaling-deficient mice also
      exhibited increased plasma corticosterone under non-stressed conditions, which
      suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the
      best of our knowledge, the present work is the first study to systematically
      compare the effects of MCH signaling on behavioral and metabolic phenotypes. 

PMID- 24924346
TI  - Dental implant surface treatments may modulate cytokine secretion in
      Porphyromonas gingivalis-stimulated human gingival fibroblasts: a comparative
      study.
AB  - Peri-implantitis is an inflammation that affects dental implants and can lead to
      implant loss. The aim of this study was to analyze the in vitro effect of
      different implant surface treatments on cytokine production by human gingival
      fibroblasts (HGFs) stimulated or not with Porphyromonas gingivalis
      lipopolysaccharide (PgLPS). Six different titanium implants were tested: turned,
      sandblasted, anodized, acid-etched, TiO2-blasted/acid-etched, and grit
      blasted/acid-etched. HGFs were seeded with each implant in a 6-well plate and
      assayed before LPS treatment (-LPS) or after 36 h of LPS (+LPS) treatment.
      Protein concentrations were measured using a Pierce bicinchoninic acid (BCA)
      assay and cytokine secretions were analyzed using a multiplex cytokine array.
      Scanning electron microscopy was performed for sterile implants and after cell
      attachment. Protein levels were consistent across all implants indicating that
      cell growth was uniform (p > 0.05). Sandblasted and turned surfaces significantly
      increased the secretion of interleukin (IL)-6, -8, -10, MCP-1 and VEGF (p < 0.05)
      when compared with the other surfaces. PgLPS stimulus increased cytokine
      secretion in all tested surfaces. In conclusion, different implant surfaces had
      various effects on HGFs' cytokine secretion. The findings may provide insights
      into the progression of peri-implantitis.

PMID- 24924347
TI  - High elastic modulus nanoparticles: a novel tool for subfailure connective tissue
      matrix damage.
AB  - Subfailure matrix injuries such as sprains and strains account for a considerable
      portion of ligament and tendon pathologies. In addition to the lack of a robust
      biological healing response, these types of injuries are often characterized by
      seriously diminished matrix biomechanics. Recent work has shown nanosized
      particles, such as nanocarbons and nanocellulose, to be effective in modulating
      cell and biological matrix responses for biomedical applications. In this
      article, we investigate the feasibility and effect of using high stiffness
      nanostructures of varying size and shape as nanofillers to mechanically reinforce
      damaged soft tissue matrices. To this end, nanoparticles (NPs) were characterized
      using atomic force microscopy and dynamic light scattering techniques. Next, we
      used a uniaxial tensile injury model to test connective tissue (porcine skin and
      tendon) biomechanical response to NP injections. After injection into damaged
      skin and tendon specimens, the NPs, more notably nanocarbons in skin, led to an
      increase in elastic moduli and yield strength. Furthermore, rat primary patella
      tendon fibroblast cell activity evaluated using the metabolic water soluble
      tetrazolium salt assay showed no cytotoxicity of the NPs studied, instead after
      21 days nanocellulose-treated tenocytes exhibited significantly higher cell
      activity when compared with nontreated control tenocytes. Dispersion of
      nanocarbons injected by solution into tendon tissue was investigated through
      histologic studies, revealing effective dispersion and infiltration in the
      treated region. Such results suggest that these high modulus NPs could be used as
      a tool for damaged connective tissue repair.

PMID- 24924348
TI  - A prospective epigenetic paradigm between cellular senescence and epithelial
      mesenchymal transition in organismal development and aging.
AB  - Epigenetic states can govern the plasticity of a genome to be adaptive to
      environments where many stress stimuli and insults compromise the homeostatic
      system with age. Although certain elastic power may autonomously reset,
      reprogram, rejuvenate, or reverse the organismal aging process, enforced genetic
      manipulations could at least reset and reprogram epigenetic states beyond
      phenotypic plasticity and elasticity in cells, which can be further manipulated
      into organisms. The question, however, remains how we can rejuvenate intrinsic
      resources and infrastructures in a noninvasive manner, particularly in a whole
      complex aging organism. Given inevitable increase of cancer with age, presumably
      any failure of resetting, reprogramming, or even rejuvenation could be a
      prominent causative factor of malignancy. Accompanied by progressive
      deteriorations of physiological functions in organisms with advancing age, aging
      associated cancer risk may essentially arise from unforeseen complications in
      cellular senescence. At the cellular level, epithelial-mesenchymal plasticity
      (dynamic and reversible transitions between epithelial and mesenchymal phenotypic
      states) is enabled by underlying shifts in epigenetic regulation. Thus, the
      epithelial-mesenchymal transition (EMT) and its reversal (mesenchymal-epithelial
      transition [MET]) function as a key of cellular transdifferentiation programs. On
      the one hand, the EMT-MET process was initially appreciated in developmental
      biology, but is now attracting increasing attention in oncogenesis and
      senescence, because the process is involved in the malignant progression vs
      regression of cancer. On the other hand, senescence is often considered the
      antithesis of early development, but yet between these 2 phenomena, there may be
      common factors and governing mechanisms such as the EMT-MET program, to steer
      toward rejuvenation of the biological aging system, thereby precisely controlling
      or avoiding cancer through epigenetic interventions.

PMID- 24924350
TI  - Spatial patterns of the congenital heart disease prevalence among 0- to 14-year
      old children in Sichuan Basin, P. R China, from 2004 to 2009.
AB  - BACKGROUND: Congenital heart disease (CHD) is the most common type of major birth
      defects in Sichuan, the most populous province in China. The detailed etiology of
      CHD is unknown but some environmental factors are suspected as the cause of this
      disease. However, the geographical variations in CHD prevalence would be highly
      valuable in providing a clue on the role of the environment in CHD etiology.
      Here, we investigate the spatial patterns and geographic differences in CHD
      prevalence among 0- to 14-year-old children, discuss the possible environmental
      risk factors that might be associated with CHD prevalence in Sichuan Basin from
      2004 to 2009. METHODS: The hierarchical Bayesian model was used to estimate CHD
      prevalence at the township level. Spatial autocorrelation statistics were
      performed, and a hot-spot analysis with different distance thresholds was used to
      identify the spatial pattern of CHD prevalence. Distribution and clustering maps
      were drawn using geographic information system tools. RESULTS: CHD prevalence was
      significantly clustered in Sichuan Basin in different spatial scale. Typical
      hot/cold clusters were identified, and possible CHD causes were discussed. The
      association between selected hypothetical environmental factors of maternal
      exposure and CHD prevalence was evaluated. CONCLUSIONS: The largest hot-spot
      clustering phenomena and the CHD prevalence clustering trend among 0- to 14-year
      old children in the study area showed a plausibly close similarity with those
      observed in the Tuojiang River Basin. The high ecological risk of heavy metal(Cd,
      As, and Pb)sediments in the middle and lower streams of the Tuojiang River
      watershed and ammonia-nitrogen pollution may have contribution to the high
      prevalence of CHD in this area.

PMID- 24924351
TI  - Factors associated with molar incisor hypomineralization in Thai children.
AB  - Molar incisor hypomineralization (MIH) is a qualitative developmental enamel
      defect that affects one to four permanent first molars, with or without
      involvement of permanent incisors. Its etiology is of systemic origin, but is not
      well understood. Therefore, we conducted this cross-sectional study to examine
      pre-, peri-, and postnatal risk factors for MIH among children, 7-8 yr of age, in
      urban areas of Khon Kaen, Thailand. Molar incisor hypomineralization defects were
      diagnosed using the European Academy of Pediatric Dentistry criteria. Mothers or
      primary caregivers were interviewed on maternal medical history and habits during
      pregnancy, pregnancy and delivery complications, and the child's medical history.
      Molar incisor hypomineralization defects were observed in 78 (27.7%) of 282
      children. Multiple logistic regression analysis showed a statistically
      significant association between the development of MIH and Cesarean section
      (adjusted OR = 2.0, 95% CI = 1.1-3.7), complications during vaginal delivery
      (adjusted OR = 4.5, 95% CI = 1.9-11.0), and severe/chronic illness when under 3
      yr of age (adjusted OR = 2.9, 95% CI = 1.6-5.0). There was no association of
      preterm birth and low birth weight with MIH. The results suggest that Cesarean
      section, complications during vaginal delivery, and poor health during the first
      3 yr of life are independent risk factors for MIH.

PMID- 24924352
TI  - Comparing cognition, mealtime performance, and nutritional status in people with
      dementia with or without ideational apraxia.
AB  - OBJECTIVE: To describe the prevalence rate of ideational apraxia (IA) affecting
      self-feeding in people with dementia, confirm the stage of dementia at which IA
      most commonly occurs, and compare mealtime performance and nutritional status
      between people with dementia (PWD) with and without IA. METHOD: A cross-sectional
      design with between-subject comparison was used. Among the 395 potential
      participants recruited from dementia special care units at nine long-term care
      facilities in central and northern Taiwan, 98 met the operational definition of
      IA and were included in the PWD with IA group. From the remaining pool, 98
      participants, matched for age and sex with the PWD with IA group, were randomly
      allocated to the PWD without IA group. Eating Behavior Scale (EBS) scores, food
      intake, total eating time, meal assistance, body mass index, Mini-Nutritional
      Assessment (MNA), and Mini-Mental State Examination scores were collected.
      RESULTS: The prevalence rate of IA affecting self-feeding in our study population
      of PWD was 24.8%. PWD with IA had significantly lower EBS scores, had more food
      intake (p < .001), spent more time being fed by caregivers, needed more verbal
      and feeding assistance, and had lower MNA scores than PWD without IA. Decline in
      the self-feeding ability of PWD affected by IA most commonly occurred in the
      severe stage of dementia. CONCLUSION: When dementia progresses to the late stage,
      staff should pay special attention to residents' mealtime performance and
      nutritional status. For PWD with IA, reassigning staff at mealtimes based on
      eating ability and providing memory training are recommended.

PMID- 24924349
TI  - Early release of high-mobility group box 1 (HMGB1) from neurons in experimental
      subarachnoid hemorrhage in vivo and in vitro.
AB  - BACKGROUND: Translocation of high-mobility group box 1 (HMGB1) from nucleus could
      trigger inflammation. Extracellular HMGB1 up-regulates inflammatory response in
      sepsis as a late mediator. However, little was known about its role in
      subarachnoid hemorrhage-inducible inflammation, especially in the early stage.
      This study aims to identify whether HMGB1 translocation occurred early after SAH
      and also to clarify the potential role of HMGB1 in brain injury following SAH.
      METHODS: Sprague-Dawley (SD) rats were randomly divided into sham group and SAH
      groups at 2 h, 12 h and on day 1, day 2. SAH groups suffered experimental
      subarachnoid hemorrhage by injection of 0.3 ml autoblood into the pre-chiasmatic
      cistern. Rats injected by recombinant HMGB1(rHMGB1) solution were divided into
      four groups according to different time points. Cultured neurons were assigned
      into control group and four hemoglobin (Hb) incubated groups. Mixed glial cells
      were cultured and stimulated in medium from neurons incubated by Hb. HMGB1
      expression is measured by western blot analysis, real-time polymerase chain
      reaction (PCR), immunohistochemistry and immunofluorescence. Downstream nuclear
      factor kappa B (NF-kappaB) subunit P65 and inflammatory factor Interleukin 1beta
      (IL-1beta) were measured by western blot and real-time PCR, respectively. Brain
      injury was evaluated by cleaved caspase-3 staining. RESULTS: Our results
      demonstrated HMGB1 translocation occurred as early as 2 h after experimental SAH
      with mRNA and protein level increased. Immunohistochemistry and
      immunofluorescence results indicated cytosolic HMGB1 was mainly located in
      neurons while translocated HMGB1 could also be found in some microglia. After
      subarachnoid injection of rHMGB1, NF-kappaB, downstream inflammatory response and
      cleaved caspase-3 were up-regulated in the cortex compared to the saline control
      group. In-vitro, after Hb incubation, HMGB1 was also rapidly released from
      neurons to medium. Incubation with medium from neurons up-regulated IL-1beta in
      mixed glial cells. This effect could be inhibited by HMGB1 specific inhibitor
      glycyrrhizic acid (GA) treatment. CONCLUSION: HMGB1 was released from neurons
      early after SAH onset and might trigger inflammation as an upstream inflammatory
      mediator. Extracellular HMGB1 contributed to the brain injury after SAH. These
      results might have important implications during the administration of specific
      HMGB1 antagonists early in order to prevent or reduce inflammatory response
      following SAH.

PMID- 24924353
TI  - Effect of atorvastatin on wound healing in rats.
AB  - Skin-wound healing is a complex and dynamic biological process involving
      inflammation, proliferation, and remodeling. Recent studies have shown that
      statins are new therapeutical options because of their actions, such as anti
      inflammatory and antioxidant activity, on vasodilation, endothelial dysfunction
      and neoangiogenesis, which are independent of their lipid-lowering action. Our
      aim was to investigate the effect of atorvastatin on tissue repair after acute
      injury in healthy animals. Rats were divided into four groups: placebo-treated
      (P), topical atorvastatin-treated (AT), oral atorvastatin-treated (AO), topical
      and oral atorvastatin-treated (ATO). Under anesthesia, rats were wounded with an
      8-mm punch in the dorsal region. Lesions were photographed on Days 0, 1, 3, 7,
      10, 12, and 14 post-injury and samples taken on Days 1, 3, 7, and 14 for protein
      expression analysis of insulin receptor substrate (IRS)-1, phosphatidylinositol 3
      kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase (GSK)-3,
      endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor
      (VEGF), extracellular signal-regulated kinase (ERK), interleukin (IL)-10, IL
      1beta, IL-6, and tumor necrosis factor (TNF)-alpha. Upon macroscopic examination,
      we observed significant reductions of lesion areas in groups AT, AO, and ATO
      compared to the P group. Additionally, AT and AO groups showed increased
      expression of IRS-1, PI3K, Akt, GSK-3, and IL-10 on Days 1 and 3 when compared
      with the P group. All atorvastatin-treated groups showed higher expression of IRS
      1, PI3K, Akt, GSK-3, IL-10, eNOS, VEGF, and ERK on Day 7. On Days 1, 3, and 7,
      all atorvastatin-treated groups showed lower expression of IL-6 and TNF-alpha
      when compared with the P group. We conclude that atorvastatin accelerated tissue
      repair of acute lesions in rats and modulated expressions of proteins and
      cytokines associated with cell-growth pathways. 

PMID- 24924355
TI  - Efficacy of tumor-targeting Salmonella typhimurium A1-R on nude mouse models of
      metastatic and disseminated human ovarian cancer.
AB  - We report here the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R)
      on mouse models of disseminated and metastatic ovarian cancer. The proliferation
      inhibitory efficacy of A1-R on human ovarian cancer cell lines (SKOV-3-GFP, OVCAR
      3-RFP) was initially demonstrated in vitro. Orthotopic and dissemination mouse
      models of ovarian cancer were made with the human ovarian cancer cell line SKOV-3
      GFP. After tumor implantation, the mice were treated with A1-R (5 * 10(7)  colony
      forming units [CFU], i.v.), and there were no severe adverse events observed. In
      the orthotopic model, tumor volume after treatment was 276 +/- 60.8 mm(3),
      compared to 930 +/- 342 mm(3) in the untreated control group (P = 0.022). There
      was also a significant difference in survival between treated mice and untreated
      mice in a peritoneal dissemination model (P = 0.005). The results of this report
      demonstrate that A1-R is effective for highly aggressive human ovarian cancer in
      metastatic and dissemination mouse models and suggest its clinical potential for
      this highly treatment-resistant disease.

PMID- 24924358
TI  - Influences of alcohol on the social responses of male resident mice to anosmic
      female intruders.
AB  - The effects of acutely administered ethanol (0, 0.5, 1.0 or 2.0 g/kg, i.p.) were
      studied in individually-housed male Swiss mice in dyadic encounters with anosmic,
      group-housed female intruders. The procedure was designed to suppress levels of
      attack in isolates. Videotape analysis of 500-second encounters, using both
      simplified and complex ethological techniques, revealed that alcohol did not
      potentiate aggression at any dose tested. At the highest alcohol dose there were
      marked increases in total time spent in timid-defensive and non-social
      behaviours, with concomitant decreases in aggressive and social/sexual
      activities. The postural analysis showed increases and decreases in elements of
      non-social behaviour and social investigatory elements, together with marked
      increases in certain timid-defensive activities and a decrease in tail-rattling.
      Comparison with previous work on inter-male paradigms shows that the type of
      opponent not only modifies the behaviour of saline-treated controls, but markedly
      influences the behavioural responses to alcohol treatment. 

PMID- 24924357
TI  - [Arthrodesis without bone fusion with an intramedullary modular nail for revision
      of infected total knee arthroplasty].
AB  - OBJECTIVE: To evaluate the outcome of knee fixation without bone fusion using an
      intramedullary modular nail and interposed cement. MATERIAL AND METHODS:
      Retrospective study of 29 infected total knee arthroplasties with prospective
      data collection and a mean follow-up of 4.2 years (3-5). RESULTS: Complications
      included 2 recurrent infections, 1 peri-implant fracture, and 1 cortical erosion
      due to the tip of the femoral component. All of these were revised with
      successful results. The mean limb length discrepancy was 0.8 cm, with 24<1cm.
      Twenty-five patients reported no pain. The mean WOMAC-pain was 86.9, WOMAC
      function 56.4, SF12-physical 45.1, and SF12-mental 53.7. Four patients needed a
      walking frame, and only two were dependent for daily activities. CONCLUSIONS: The
      Endo-Model Link nail is an effective method for knee fixation that restores the
      anatomical alignment of the limb with adequate leg length.

PMID- 24924356
TI  - Omics-based interpretation of synergism in a soil-derived cellulose-degrading
      microbial community.
AB  - Reaching a comprehensive understanding of how nature solves the problem of
      degrading recalcitrant biomass may eventually allow development of more efficient
      biorefining processes. Here we interpret genomic and proteomic information
      generated from a cellulolytic microbial consortium (termed F1RT) enriched from
      soil. Analyses of reconstructed bacterial draft genomes from all seven uncultured
      phylotypes in F1RT indicate that its constituent microbes cooperate in both
      cellulose-degrading and other important metabolic processes. Support for
      cellulolytic inter-species cooperation came from the discovery of F1RT microbes
      that encode and express complimentary enzymatic inventories that include both
      extracellular cellulosomes and secreted free-enzyme systems. Metabolic
      reconstruction of the seven F1RT phylotypes predicted a wider genomic rationale
      as to how this particular community functions as well as possible reasons as to
      why biomass conversion in nature relies on a structured and cooperative microbial
      community. 

PMID- 24924359
TI  - Long-term retention of a poorly learned saccharin aversion : Evidence for an
      incubation effect.
AB  - The retention of a weak conditioned saccharin aversion was tested using
      independent groups over a 14-day period. The delay between CS (saccharin 0.1 %)
      and US (LiCl 0.15 M) was 6 hours. Significant variations in the retention
      function were observed, in particular an improvement of memory - i.e. an
      incubation effect - over the 14-day period. This result suggests that retention
      of conditioned taste aversion may share common features with the retention of
      more classical aversive conditioning. 

PMID- 24924360
TI  - Grouped sequential exploitation of food patches in a flock feeder, the feral
      pigeon.
AB  - Feral and laboratory flocks of rock doves (Columba livia ) show a pattern of
      grouped sequential exploitation when simultaneously presented with two dispersed,
      depleting patches of seed. This behavior contrasts with the ideal free
      distribution pattern shown when patches are small and concentrated. Grouped
      sequential exploitation consists of two phases: all pigeons first land together
      and feed at one patch, then leave one by one for the other patch. Departure times
      of individuals for the second patch are correlated with feeding rate at patch 1,
      which is in turn correlated with position in the dominance hierarchy. The
      decision to switch from patch 1 to patch 2 improves individual feeding rates in
      all cases, but is done slightly later than it should according to optimal
      foraging theory. 

PMID- 24924361
TI  - Food neophobia in wild and laboratory mice (Mus musculus domesticus).
AB  - In a conditioned taste aversion procedure we were specifically interested in the
      topic of food neophobia. Wild and laboratory mice were individually presented
      with a novel drink (0.1 % saccharin solution). Compared with the daily water
      consumption, the intake of this was lower. This decrease was greater: (1) in wild
      than in tame populations ; (2) in random-bred (Swiss-albinos) than in inbred (C57
      B1/6, BALB/c) strains ; (3) in F1-hybrids (either wild x tame or inbred x inbred)
      than in the parental strains. These results are discussed: (1) in terms of a
      selective pressure linked to man's fight against rodents, leading to increased
      neophobia in wild mice ; and (2) by stressing the heterosis an inbreeding
      depression effects, which suggest that food neophobia is a component of Darwinian
      fitness. 

PMID- 24924362
TI  - Bliss points vs. minimum needs: Tests of competing motivational models.
AB  - This paper tests two competing hypotheses concerning the motivational forces
      underlying concurrent choice behavior: a generalized version of Staddon's minimum
      distance hypothesis, which characterizes behavior in terms of minimizing the
      distance to a "bliss" point, and a generalized minimum-needs hypothesis, which
      emphasizes meeting minimum survival requirements first, after which the organism
      is free to allocate behavior in any fashion desired. The models specify
      distinctly different preference structures. The generalized minimum-needs
      hypothesis is shown to provide a superior fit to molar choice data from
      experiments involving food and fluid consumption. 

PMID- 24924363
TI  - Effects of lateral hypothalamic stimulation on acquisition, reversal and
      extinction of a visual discriminative learning task.
AB  - The present experiment was carried out to investigate the effects of lateral
      hypothalamic (LH) stimulation on a negatively reinforced complex learning task
      including acquisition, reversal and extinction of a visual discrimination in an Y
      maze. Male swiss mice were stimulated 45 sec after each training session during
      60 sec (group ST). The stimulation intensity administrated in post-session was
      that which produced a rate of 50 responses by min during intracranial self
      stimulation (ICSS) testing carried out prior to the learning experiment. Three
      control groups were constituted by animals either submitted to ICSS testing but
      not stimulated after training session (group NST). The post-session stimulated
      (group I) or non-implanted (group NI). The post-session stimulation improved the
      learning performance of the animals, but this effect was significant only during
      reversal learning of the task. ICSS testing carried out before learning, as well
      as electrode implantation, had no effect by themselves on the acquisition of the
      visual discrimination task. Moreover, no sign of extinction was observed in any
      group tested. These results suggest that facilitating effects induced by LH
      stimulation may depend on the complexity of the task and that cues of the
      learning situation have to reach a minimum of salience in order for LH
      stimulation to be effective. 

PMID- 24924364
TI  - Social development in three species of macaque (Macaca mulatta , M. fascicularis
      , M. tonkeana ): A preliminary report on the first ten weeks of life.
AB  - The development of social relations was studied in 11 infant monkeys over the
      first ten weeks of life : 5 subjects in a rhesus macaque group (Macaca mulatta ),
      3 in a long-tailed macaque group (M. fascicularis ) and 3 in a Tonkean macaque
      group (M. tonkeana ). Tonkean infants were found to interact with many different
      group members because of the permissiveness of their mothers, while social
      contacts of rhesus and long-tailed infants are less varied due to the
      restrictiveness of their mothers. These differences were consistent with patterns
      of adult-adult interactions, Tonkean macaques showing less intense agonistic
      interactions than the other two species. 

PMID- 24924365
TI  - An attempt to select for spontaneous locomotor activity in Drosophila
      melanogaster.
AB  - Seven generations of selection for high and low spontaneous locomotor activity
      were made in the wild-laboratory strain Oregon of Drosophila melanogaster. Great
      care was taken to select for activity and not for reactivity. In opposition with
      the non totally unambiguous results obtained by another author, absolutely no
      response to selection could be obtained. Thus the Oregon strain of Drosophila
      melanogaster does not appear to possess any additive genetic variance for
      spontaneous locomotor activity. Yet before taking for granted that that
      conclusion is applicable to all strains of Drosophila melanogaster an
      experimental selection should be performed again using a freshly captured wild
      strain. 

PMID- 24924373
TI  - Female mate choice in the pupfish, Cyprinodon variegatus.
AB  - Experimental evidence suggests that female Cyprinodon variegatus do not select
      between competitively inferior and superior males, but rather, deposit eggs
      randomly and in proportion to the size of the male's territory. The females do
      seem to have an habitat preference and probably influence the location where
      males compete for territorial space. 

PMID- 24924374
TI  - Central and peripheral action of testosterone propionate on scent gland
      morphology and marking behaviour in the Mongolian gerbil.
AB  - Scent gland size and activity and frequency of marking under standard conditions
      were compared in five groups of male and female gerbils: (1) intact, sham
      operated controls, (2) intact with scent glands excised, (3) gonadectomized, (4)
      gonadectomized injected with 1000 MUg testosterone propionate (TP) on alternate
      days, and (5) gonadectomized with a low dose (25 MUg) TP applied topically to the
      ventral scent gland on alternate days. The animals were housed in individual
      cages and tested for marking in an open field arena with plastic pegs. The scent
      gland is not required in either sex for the behavioural act of marking. Topical
      application of a dose of TP too low to exert a systematic effect restored the
      scent gland but not marking. Injection of sufficient TP to restore seminal
      vesicle weight restored marking, as well as the scent glands. It was concluded
      that in the male, both marking behaviour and scent gland size are controlled by
      the testes. The effect of androgens on marking is mediated directly through the
      central nervous system, and not through peripheral stimulation of the glands.
      Females have smaller glands and mark less than males. The ovaries appear to have
      little control over marking frequency, and some control over scent gland size. It
      is possible to stimulate marking behaviour to supernormal levels by TP injection,
      but not by topical application. 

PMID- 24924375
TI  - Sequences of feeding, sampling and exploration by wild and laboratory rats.
AB  - Adult male wild rats and male laboratory rats, all Rattus norvegicus, were kept
      alone for 11 d is a residential maze. The maze had a central nest box and four
      arms radiating from it. Movement in the arms was automatically recorded. Three
      foods were supplied, one at the end of each of three arms; the fourth arm was
      empty. One food was usually much preferred to the othe two. Except on Days 1-3,
      access to the arms was for only 3h daily. The rate of visiting the arms declined
      during the first 3 d. The wild rats were more 'active' than the domestic in that
      they made more visits; but they spent less time in the arms. Visits were of two
      kinds: (a) short, usually < 1min; (b) long (> 4 min.: meals). The wild rats had
      shorter meals than the donestic. A 3-h period of access usually began with a bout
      of short visits to the arms. Each long visit to a food arm (a meal) was also
      typically followed by such a bout, sometimes after a period in the nest box
      (drinking). the first short visit after a meal by a wild rat was most often to
      the empty arm; but domestic rats distributed these visits evenly among the three
      arms in which they had not been feeding. In a given bout the second short visit
      by a wild rat, but not a domestic, tended to repeat the first. We interpret a
      bout of short visits as a patrol or re-exploration of the living space which may
      include sampling of all accessible foods. When a bout occured at the beginning of
      access to the maze arms, exploring was in 'competition' with eating; a bout after
      a meal may have represented 'disinhibition' of exploring. 

PMID- 24924376
TI  - Non-reproducibility of the behavioural effects induced by scotophobin.
AB  - Three different samples of scotophobin were tested successively on the light/dark
      preference test and emotional reactivity of mice. Only one of these samples gave
      results similar to those described previously by Ungar et al. (1972). The lack of
      reproductibility of the effects of this peptide is discussed. 

PMID- 24924377
TI  - Circadian periodicity of escape behaviour in the mouse: Preliminary
      chronobiological data.
AB  - The cosinor methodology previously applied to different studies within the field
      of ethological rhythms is used in the present report to assess the circadian
      rhythm of escape behaviour. The peak frequency is located toward the end of the
      dark span in mice exposed to light between 08.00 and 20.00 h. Such experiments
      provide a quantitative approach for studying some neurobiological mechanisms
      regulating adaptive behaviour. 

PMID- 24924380
TI  - Les livrees ou patrons de coloration chez les poissons Cichlides Africains. Leur
      utilisation en ethologie et en systematique J. Voss, Universite de Liege
      (Belgium). Revue Francaise d'Aquariologie, 4e annee, No. 2, 2e trimestre 1977.

PMID- 24924382
TI  - Leg general muscle moment and power patterns in able-bodied subjects during
      recumbent cycle ergometry with ankle immobilization.
AB  - Rehabilitation of persons with pareses commonly uses recumbent pedalling and a
      rigid pedal boot that fixes the ankle joint from moving. This study was performed
      to provide general muscle moments (GMM) and joint power data from able-bodied
      subjects performing recumbent cycling at two workloads. Twenty-six able-bodied
      subjects pedalled a stationary recumbent tricycle at 60 rpm during passive
      cycling and at two workloads (low 15 W and high 40 W per leg) while leg
      kinematics and pedal forces were recorded. GMM and power were calculated using
      inverse dynamic equations. During the high workload, the hip and knee muscles
      produced extensor/flexor moments throughout the extensions/flexions phases of the
      joints. For low workload, a prolonged (crank angle 0-258 degrees ) hip extension
      moment and a shortened range (350-150 degrees ) of knee extension moment were
      observed compared to the corresponding extension phases of each joint. The knee
      and hip joints generated approximately equal power. At the high workload the hip
      and knee extensors generated increased power in the propulsion phase. For the
      first time, this study provides GMM and power patterns for able-bodied subjects
      performing recumbent cycling with an immobilized ankle. The patterns showed
      greater similarities to upright cycling with a free ankle, than previously
      supposed.

PMID- 24924383
TI  - Validation of a numerical FSI simulation of an aortic BMHV by in vitro PIV
      experiments.
AB  - In this paper, a validation of a recently developed fluid-structure interaction
      (FSI) coupling algorithm to simulate numerically the dynamics of an aortic
      bileaflet mechanical heart valve (BMHV) is performed. This validation is done by
      comparing the numerical simulation results with in vitro experiments. For the in
      vitro experiments, the leaflet kinematics and flow fields are obtained via the
      particle image velocimetry (PIV) technique. Subsequently, the same case is
      numerically simulated by the coupling algorithm and the resulting leaflet
      kinematics and flow fields are obtained. Finally, the results are compared,
      revealing great similarity in leaflet motion and flow fields between the
      numerical simulation and the experimental test. Therefore, it is concluded that
      the developed algorithm is able to capture very accurately all the major leaflet
      kinematics and dynamics and can be used to study and optimize the design of
      BMHVs. 

PMID- 24924384
TI  - When does hardship matter for health? Neighborhood and individual disadvantages
      and functional somatic symptoms from adolescence to mid-life in The Northern
      Swedish Cohort.
AB  - A large body of research has shown that health is influenced by disadvantaged
      living conditions, including both personal and neighborhood conditions. Little is
      however known to what degree the health impact of different forms of disadvantage
      differ along the life course. The present study aims to examine when, during the
      life course, neighborhood and individual disadvantages relate to functional
      somatic symptoms. Participants (n = 992) came from The Northern Swedish Cohort
      and followed from age 16, 21, 30 until 42 years. Functional somatic symptoms,
      socioeconomic disadvantage, and social and material adversity were measured
      through questionnaires and linked to register data on neighborhood disadvantage.
      Data was analyzed with longitudinal and cross-sectional multilevel models.
      Results showed that neighborhood disadvantage, social and material adversity and
      gender all contributed independently to overall levels of symptoms across the
      life course. Cross-sectional analyses also suggested that the impact of
      disadvantage differed between life course periods; neighborhood disadvantage was
      most important in young adulthood, and the relative importance of material versus
      social adversity increased as participants grew older. In summary, the study
      suggests that disadvantages from different contextual sources may affect
      functional somatic health across the life course, but also through life course
      specific patterns. 

PMID- 24924385
TI  - Prevention of disease progression with anti-inflammatory therapy in patients with
      HCV-related cirrhosis: a Markov model.
AB  - BACKGROUND: The significance of anti-inflammatory therapy has not been fully
      evaluated in hepatitis C virus (HCV)-related cirrhosis. PATIENTS AND METHODS: We
      analyzed stepwise progression rates from cirrhosis to hepatocellular carcinoma
      (HCC) and to death using a Markov model in 1,280 patients with HCV-related
      cirrhosis. During the observation period, 303 patients received interferon and
      736 received glycyrrhizin injections as anti-inflammatory therapy. RESULTS: In
      the entire group, annual progression rates from cirrhosis to HCC and from
      cirrhosis to death were 6.8 and 1.9%, and the rate from HCC to death was 19.0%.
      When sustained virological response (SVR) or biochemical response (BR) was
      attained with interferon, the annual rate to HCC decreased to 2.6%. On the
      contrary, the progression rates to HCC and to death in the patients without SVR
      and BR were 7.2 and 2.0%, respectively (p < 0.0001). Continuous interferon
      administration significantly decreased the carcinogenesis rate to 5.5% (p =
      0.0087). In the analysis of the remaining patients with high alanine transaminase
      of 75 IU/l or more but without interferon response or without interferon
      administration, glycyrrhizin injection significantly decreased annual non
      progression probability (no glycyrrhizin 88.0% vs. glycyrrhizin therapy 92.3%, p
      = 0.00055). CONCLUSION: Glycyrrhizin injection therapy is useful in the
      prevention of disease progression in interferon-resistant or intolerant patients
      with HCV-related cirrhosis.

PMID- 24924386
TI  - Evaluation of calibration curve-based approaches to predict clinical inducers and
      noninducers of CYP3A4 with plated human hepatocytes.
AB  - Cytochrome P450 (P450) induction is often considered a liability in drug
      development. Using calibration curve-based approaches, we assessed the induction
      parameters R3 (a term indicating the amount of P450 induction in the liver,
      expressed as a ratio between 0 and 1), relative induction score, Cmax/EC50, and
      area under the curve (AUC)/F2 (the concentration causing 2-fold increase from
      baseline of the dose-response curve), derived from concentration-response curves
      of CYP3A4 mRNA and enzyme activity data in vitro, as predictors of CYP3A4
      induction potential in vivo. Plated cryopreserved human hepatocytes from three
      donors were treated with 20 test compounds, including several clinical inducers
      and noninducers of CYP3A4. After the 2-day treatment, CYP3A4 mRNA levels and
      testosterone 6beta-hydroxylase activity were determined by real-time reverse
      transcription polymerase chain reaction and liquid chromatography-tandem mass
      spectrometry analysis, respectively. Our results demonstrated a strong and
      predictive relationship between the extent of midazolam AUC change in humans and
      the various parameters calculated from both CYP3A4 mRNA and enzyme activity. The
      relationships exhibited with non-midazolam in vivo probes, in aggregate, were
      unsatisfactory. In general, the models yielded better fits when unbound rather
      than total plasma Cmax was used to calculate the induction parameters, as
      evidenced by higher R(2) and lower root mean square error (RMSE) and geometric
      mean fold error. With midazolam, the R3 cut-off value of 0.9, as suggested by US
      Food and Drug Administration guidance, effectively categorized strong inducers
      but was less effective in classifying midrange or weak inducers. This study
      supports the use of calibration curves generated from in vitro mRNA induction
      response curves to predict CYP3A4 induction potential in human. With the caveat
      that most compounds evaluated here were not strong inhibitors of enzyme activity,
      testosterone 6beta-hydroxylase activity was also demonstrated to be a strong
      predictor of CYP3A4 induction potential in this assay model. 

PMID- 24924387
TI  - Interindividual variations in metabolism and pharmacokinetics of 3-(6
      methylpyridine-3-yl-sulfanyl)-6-(4H-[1,2,4]triazole-3-yl-sulfanyl)-N-(1,3
      thiazole-2-yl)-2-pyridine carboxamide, a glucokinase activator, in rats caused by
      the genetic polymorphism of CYP2D1.
AB  - 3-(6-Methylpyridine-3-yl-sulfanyl)-6-(4H-[1,2,4]triazole-3-yl-sulfanyl)-N-(1,3
      thiazole-2-yl)-2-pyridine carboxamide (Cpd-D) is a novel glucokinase activator
      that is being developed for the treatment of type 2 diabetes. Large
      interindividual variations were observed in the pharmacokinetics of Cpd-D in male
      Sprague-Dawley (SD) rats, which were subsequently divided into two phenotypes; >6
      fold longer terminal-phase half-life and ~10-fold larger AUC0-infinity values
      were observed in slow metabolizers (SM) than in fast metabolizers (FM) after the
      oral administration of Cpd-D. The thiohydantoic acid analog (M2) was the
      predominant metabolite detected in the urine, bile, and plasma after the oral
      administration of [(14)C]Cpd-D to the FM phenotypes of bile-duct cannulated SD
      rats. The liver microsomes prepared from FM phenotyped rats extensively formed M2
      with the highest affinity (Km = 0.09 MUM) and largest Vmax/Km value in primary
      metabolism, whereas those from SM phenotypes had little capacity to form M2. Of
      the rat cytochrome P450 isoforms tested, the formation of M2 was only catalyzed
      by recombinant CYP2D1. Sequence substitutions (418A/421C and 418G/421T) were
      detected in the CYP2D1 gene and were designated F and S alleles, respectively.
      The genotype-phenotype correlation analysis indicated that two S alleles were
      homozygous (S/S) in the SM phenotypes, whereas the FM phenotypes were either
      homozygous for the F-alleles (F/F) or heterozygous (F/S). These results indicated
      that the CYP2D1 polymorphism caused by nucleotide substitutions (418A/421C versus
      418G/421T) was responsible for interindividual variations leading to the
      polymorphism in the major metabolism and pharmacokinetics of Cpd-D in male SD
      rats. 

PMID- 24924388
TI  - Cell culture's spider silk road.
AB  - A number of synthetic and natural materials have been tried in cell culture and
      tissue engineering applications in recent years. Now Jeffrey Perkel takes a look
      at one new culture component that might surprise you-spider silk. 

PMID- 24924389
TI  - Library construction for ancient genomics: single strand or double strand?
AB  - A novel method of library construction that takes advantage of a single-stranded
      DNA ligase has been recently described and used to generate high-resolution
      genomes from ancient DNA samples. While this method is effective and appears to
      recover a greater fraction of endogenous ancient material, there has been no
      direct comparison of results from different library construction methods on a
      diversity of ancient DNA samples. In addition, the single-stranded method is
      limited by high cost and lengthy preparation time and is restricted to the
      Illumina sequencing platform. Here we present in-depth comparisons of the
      different available library construction methods for DNA purified from 16 ancient
      and modern faunal and human remains, covering a range of different taphonomic and
      climatic conditions. We further present a DNA purification method for ancient
      samples that permits the concentration of a large volume of dissolved extract
      with minimal manipulation and methodological improvements to the single-stranded
      method to render it more economical and versatile, in particular to expand its
      use to both the Illumina and the Ion Torrent sequencing platforms. We show that
      the single-stranded library construction method improves the relative recovery of
      endogenous to exogenous DNA for most, but not all, of our ancient extracts. 

PMID- 24924390
TI  - MDC-Analyzer: a novel degenerate primer design tool for the construction of
      intelligent mutagenesis libraries with contiguous sites.
AB  - Recent computational and bioinformatics advances have enabled the efficient
      creation of novel biocatalysts by reducing amino acid variability at hot spot
      regions. To further expand the utility of this strategy, we present here a tool
      called Multi-site Degenerate Codon Analyzer (MDC-Analyzer) for the automated
      design of intelligent mutagenesis libraries that can completely cover user
      defined randomized sequences, especially when multiple contiguous and/or adjacent
      sites are targeted. By initially defining an objective function, the possible
      optimal degenerate PCR primer profiles could be automatically explored using the
      heuristic approach of Greedy Best-First-Search. Compared to the previously
      developed DC-Analyzer, MDC-Analyzer allows for the existence of a small amount of
      undesired sequences as a tradeoff between the number of degenerate primers and
      the encoded library size while still providing all the benefits of DC-Analyzer
      with the ability to randomize multiple contiguous sites. MDC-Analyzer was
      validated using a series of randomly generated mutation schemes and experimental
      case studies on the evolution of halohydrin dehalogenase, which proved that the
      MDC methodology is more efficient than other methods and is particularly well
      suited to exploring the sequence space of proteins using data-driven protein
      engineering strategies. 

PMID- 24924391
TI  - Off-on polyadenylation strategy as a supplemental mechanism for silencing toxic
      transgene expression during lentiviral vector production.
AB  - Many gene therapy strategies rely on lentiviral-mediated transfer and expression
      of genes coding for toxic proteins. Methods of controlling transgene expression
      in target cells have been extensively investigated, but comparatively little
      attention has been given to controlling toxic protein expression in viral vector
      producing cells, despite its potential implications for viral production and
      transduction efficiency. In this work, we tested a new lentiviral vector with a
      backbone that inhibits transgene mRNA polyadenylation and subsequent transgene
      expression in vector-producing cells. Transgene mRNA polyadenylation was not
      affected in transduced cells. In a model using enhanced green fluorescent protein
      (EGFP) cDNA under the control of the human phosphoglycerate kinase (PGK)
      promoter, flow cytometry demonstrated that transgene expression was dramatically
      decreased in 293T cells transfected with this new vector in its plasmid
      configuration. Viral production was maintained, and expression was fully restored
      in transduced HuH7 and 293T cells. These results provide the basis for a new
      strategy to improve the production of lentiviral vectors expressing toxic
      transgenes. 

PMID- 24924392
TI  - Simultaneous quantification of alternatively spliced transcripts in a single
      droplet digital PCR reaction.
AB  - Human telomerase reverse transcriptase (hTERT) is an essential component required
      for telomerase activity and telomere maintenance. Several alternatively spliced
      forms of hTERT mRNA have been reported in human primary and tumor cells.
      Currently, however, there is no sensitive and accurate method for the
      simultaneous quantification of multiple alternatively spliced RNA transcripts,
      such as in the case of hTERT. Here we show droplet digital PCR (ddPCR) provides
      sensitive, simultaneous digital quantification in a single reaction of two
      alternatively spliced single deletion hTERT transcripts (alpha-/beta+ and
      alpha+/beta-) as well as the opportunity to manually quantify non-deletion
      (alpha+/beta+) and double deletion (alpha-/beta-) transcripts. Our ddPCR method
      enables direct comparison among four alternatively spliced mRNAs without the need
      for internal standards or multiple primer pairs specific for each variant as real
      time PCR (qPCR) requires, thus eliminating potential variation due to differences
      in PCR amplification efficiency.

PMID- 24924393
TI  - A simple approach for classifying new mutations as somatic or germinal in DNA
      samples lacking paired tissue.
AB  - When studying mutations in DNA samples, determining whether novel sequence
      changes are somatic mutations or germline polymorphisms can be difficult. Here we
      describe a novel and very simple approach for identification of somatic mutations
      and loss of heterozygosity (LoH) events in DNA samples where no matched tissue
      sample is available. Our method makes use of heterozygous polymorphisms that are
      located near the putative mutation to trace both germinal alleles. 

PMID- 24924394
TI  - Expression and purification of bioactive, low-endotoxin recombinant human
      vitronectin.
AB  - The secreted adhesive glycoprotein vitronectin (VTN) is a multifunctional
      component of plasma and the extracellular matrix. A high-yielding, inexpensive,
      low endotoxin source of bioactive recombinant human vitronectin (rhVTN) is highly
      desirable for in vitro use in diverse cell culture systems ranging from basic
      research settings to clinical-grade production of human cells. We describe
      modifications to a previously reported heparin-based affinity chromatography
      procedure that improve yield and achieve efficient removal of endotoxin from
      washed and urea-solubilized human VTN inclusion bodies following standard
      autoinduction of expression in Escherichia coli. This simple procedure makes
      accessible the low-cost expression and purification of large quantities of
      bioactive rhVTN using basic equipment and facilitates its use in a spectrum of
      endotoxin-sensitive applications. 

PMID- 24924395
TI  - Effects of renal sympathetic denervation and angiotensin-converting enzyme
      inhibitor on left ventricular hypertrophy. Comparison in spontaneously
      hypertensive rats.
AB  - OBJECTIVES: The aim of this study was to investigate whether renal sympathetic
      denervation (RSD) is more effective on myocardial hypertrophy than the
      angiotensin-converting enzyme inhibitor (ACEI) perindopril in spontaneously
      hypertensive rats (SHRs). METHODS: After bilateral renal denervation blood
      pressure (BP) was measured every 10 days. On day 50 the heart was
      (histo)pathologically examined. The ventricular weight to body weight ratios
      (VW/BW), myocardial diameter and collagen volume fraction (CVF) were calculated,
      and cardiac hypertrophy marker genes were analyzed by RT-PCR. RESULTS: At the
      baseline evaluation all groups had comparable BP. After treatment the BP of the
      RSD group was significantly reduced (p < 0.05). The BP of the RSD group was lower
      than that of the perindopril group on days 10, 20 and 30th (p < 0.05) but on day
      50 systolic BP of the RSD group was significantly higher (p < 0.05) whereas there
      were no significant differences in diastolic BP. The VW/BW decreased in the RSD
      group, whereas the value did not change significantly in the perindopril group.
      The myocardial diameter of the left ventricular cardiomyocytes was also
      significantly lower in the RSD group and stayed the same in the perindopril
      group. Collagen volume fraction (CVF) in the RSD group was significantly lower
      than in the perindopril group (p < 0.05). Significant changes in the expression
      levels of NPPA, MYH7, and MYH6 (P < 0.05) were observed in the RD-SHR groups (p <
      0.05). There was a significant difference in the expression level of MYH6 (p <
      0.05) between the RSD group and the perindopril group but the expression levels
      of NPPA and MYH7 were not significantly different. CONCLUSION: In this study, RSD
      had a significant antihypertensive effect and inhibited hypertensive-induced
      cardiac hypertrophy in SHRs and showed advantages compared with ACEI in
      decreasing BP in the early stage and in inhibiting myocardial fibrosis.

PMID- 24924396
TI  - Relationship of galectin-3 to left ventricular geometry and hypertrophy in
      chronic hemodialysis patients.
AB  - AIM AND BACKGROUND: Galectin-3 (Gal-3) is used to determine the prognosis of
      heart failure. Some studies revealed that Gal-3 promoted cardiac hypertrophy but
      there is no study in which the relationship between Gal-3 and left ventricular
      hypertrophy (LVH) geometry in patients without diastolic and systolic function
      impairment has been explored. The aim of the study was to analyze associations
      between plasma Gal-3 levels, LVH, and LV geometry in maintenance hemodialysis
      (HD) patients without systolic and diastolic dysfunction. PATIENTS AND METHODS:
      The study group included 105 patients (53 women and 52 men)--with an average age
      of 58.2 +/- 12.6 years, treated with HD for an average of 45 +/- 32 months--and
      60 healthy controls. The Gal-3 and other biochemical parameters were measured and
      color Doppler echocardiography was performed. For this study LVH was considered
      present when the LV mass index (LVMI) exceeded 95 g/m(2) in women and 115 g/m(2)
      in men. Left ventricular geometry was classified into the four groups on the
      basis of left ventricular mass and relative wall thickness (RWT). RESULTS:
      Concentric hypertrophy (CH, 40.9 %, n = 43) was the commonest geometric pattern
      in our study. The Gal-3 levels in CH patients were not different from the
      patients with eccentric hypertrophy (EH). Plasma levels of Gal-3 correlated with
      LVMI (r = 0.617, p < 0.001), parathyroid hormone (PTH, r = 0.408, p < 0.001),
      uric acid (r = 0.281, p = 0.004), C-reactive protein (CRP, r = 0.412, p < 0.001),
      and RWT (r = 0.281, p = 0.004) but were inversely correlated with albumin (r = -
      0.466, P < 0.001) in the whole group. Plasma levels of Gal-3 were associated with
      LVMI (r = 0.812, P < 0.001), RWT (r = 0.318, p = 0.001), and CRP(r = 0.381, p <
      0.001) in maintenance hemodialysis patients. CONCLUSION: The Gal-3 level is
      related to left ventricular hypertrophy and it is independent of left ventricle
      geometry. The relationship between LVH and Gal-3 might be direct or it may also
      be inflammation-related.

PMID- 24924397
TI  - Resveratrol and clofarabine induces a preferential apoptosis-activating effect on
      malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation.
AB  - We previously demonstrated that resveratrol and clofarabine elicited a marked
      cytotoxicity on malignant mesothelioma (MM) MSTO-211H cells but not on the
      corresponding normal mesothelial MeT-5A cells. Little is known of the possible
      molecules that could be used to predict preferential chemosensitivity on MSTO
      211H cells. Resveratrol and clofarabine induced down-regulation of Mcl-1 protein
      level in MSTO-211H cells. Treatment of cells with cycloheximide in the presence
      of proteasome inhibitor MG132 suggested that Mcl-1 protein levels were regulated
      at the post-translational step. The siRNA-based knockdown of Mcl-1 in MSTO-211H
      cells triggered more growth-inhibiting and apoptosis-inducing effects with the
      resultant cleavages of procaspase-3 and its substrate PARP, increased caspase-3/7
      activity, and increased percentage of apoptotic propensities. However, the
      majority of the observed changes were not shown in MeT-5A cells. Collectively,
      these studies indicate that the preferential activation of caspase cascade in
      malignant cells might have important applications as a therapeutic target for MM.

PMID- 24924398
TI  - Cellular ubiquitin pool dynamics and homeostasis.
AB  - Ubiquitin (Ub) is a versatile signaling molecule that plays important roles in a
      variety of cellular processes. Cellular Ub pools, which are composed of free Ub
      and Ub conjugates, are in dynamic equilibrium inside cells. In particular,
      increasing evidence suggests that Ub homeostasis, or the maintenance of free Ub
      above certain threshold levels, is important for cellular function and survival
      under normal or stress conditions. Accurate determination of various Ub species,
      including levels of free Ub and specific Ub chain linkages, have become possible
      in biological specimens as a result of the introduction of the proteomic approach
      using mass spectrometry. This technology has facilitated research on dynamic
      properties of cellular Ub pools and has provided tools for in-depth investigation
      of Ub homeostasis. In this review, we have also discussed the consequences of the
      disruption of Ub pool dynamics and homeostasis via deletion of polyubiquitin
      genes or mutations of deubiquitinating enzymes. The common consequence was a
      reduced availability of free Ub and a significant impact on the function and
      viability of cells. These observations further indicate that the levels of free
      Ub are important determinants for cellular protection.

PMID- 24924399
TI  - Re: Vanadium exposure-induced neurobehavioral alterations among Chinese workers
      Li et al. (2013).

PMID- 24924400
TI  - Toxicity of nanoparticles embedded in paints compared with pristine nanoparticles
      in mice.
AB  - The unique physical and chemical properties of nanomaterials have led to their
      increased use in many industrial applications, including as a paint additive. For
      example, titanium dioxide (TiO2) engineered nanoparticles (ENPs) have well
      established anti-UV, self-cleaning, and air purification effects. Silver (Ag)
      ENPs are renowned for their anti-microbial capabilities and silicon dioxide
      (SiO2) ENPs are used as fire retardants and anti-scratch coatings. In this study,
      the toxic effects and biodistribution of three pristine ENPs (TiO2, Ag, and
      SiO2), three aged paints containing ENPs (TiO2, Ag, and SiO2) along with control
      paints without ENPs were compared. BALB/c mice were oropharyngeally aspirated
      with ENPs or paint particles (20 MUg/aspiration) once a week for 5 weeks and
      sacrificed either 2 or 28 days post final aspiration treatment. A bronchoalveolar
      lavage was performed and systemic blood toxicity was evaluated to ascertain cell
      counts, induction of inflammatory cytokines, and key blood parameters. In
      addition, the lung, liver, kidney, spleen, and heart were harvested and metal
      concentrations were determined. Exposure to pristine ENPs caused subtle effects
      in the lungs and negligible alterations in the blood. The most pronounced toxic
      effects were observed after Ag ENPs exposure; an increased neutrophil count and a
      twofold increase in pro-inflammatory cytokine secretion (keratinocyte
      chemoattractant (KC) and interleukin-1beta (IL-1beta)) were identified. The paint
      containing TiO2 ENPs did not modify macrophage and neutrophil counts, but mildly
      induced KC and IL-1beta. The paints containing Ag or SiO2 did not show
      significant toxicity. Biodistribution experiments showed distribution of Ag and
      Si outside the lung after aspiration to respectively pristine Ag or SiO2 ENPs. In
      conclusion, we demonstrated that even though direct exposure to ENPs induced some
      toxic effects, once they were embedded in a complex paint matrix little to no
      adverse toxicological effects were identified. 

PMID- 24924401
TI  - Loss of Nrf2 in mice evokes a congenital intrahepatic shunt that alters hepatic
      oxygen and protein expression gradients and toxicity.
AB  - The transcription factor Nrf2 (Nfe2l2 nuclear factor, erythroid 2-like 2)
      regulates gene expression directly, controlling pharmacological and toxicological
      responses. These processes may also be influenced by the structure of the hepatic
      vasculature, which distributes blood flow through compartmentalized
      microenvironments to maintain organismal stability. Castings of the hepatic
      portal vasculature of albino C57BL/6J but not ICR Nrf2(-/-) mice revealed a
      congenital intrahepatic shunt that was present in two thirds of Nrf2-disrupted
      mice. This shunt directly connected the portal vein to the inferior vena cava and
      displayed characteristics of a patent ductus venosus. Immunohistochemistry
      revealed that Nrf2(-/-) mice with an intrahepatic shunt manifest changes to
      hepatic oxygen and protein expression gradients when compared with wild-type (WT)
      and non-shunted Nrf2(-/-) mice. Centrilobular hypoxia found in WT and Nrf2(-/-)
      mice without shunts was reduced in Nrf2(-/-) livers with a shunt. Hepatic protein
      expression of phosphoenolpyruvate carboxykinase (Pepck), normally confined to the
      periportal zone, exhibited both periportal and centrilobular zonal expression in
      livers from Nrf2(-/-) mice with an intrahepatic shunt. Centrilobular expression
      of Cytochrome P450 2E1 (Cyp2e1) was diminished in shunted Nrf2(-/-) livers
      compared with WT and Nrf2(-/-) livers without shunts. The intrahepatic shunt in
      Nrf2(-/-) mice was further found to diminish acetaminophen hepatoxicity compared
      with WT and Nrf2(-/-) non-shunted mice following a 6 h challenge with 250 mg/kg
      acetaminophen. The presence of an intrahepatic shunt influences several
      physiological and pathophysiological properties of Nrf2(-/-) mice through changes
      in blood flow, hepatic oxygenation, and protein expression that extent beyond
      loss of canonical transactivation of Nrf2 target genes. 

PMID- 24924402
TI  - Arsenic exposure and cell-mediated immunity in pre-school children in rural
      Bangladesh.
AB  - Prenatal arsenic exposure has been associated with reduced thymic index and
      increased morbidity in infants, indicating arsenic-related impaired immune
      function. We aimed at elucidating potential effects of pre- and postnatal arsenic
      exposure on cell-mediated immune function in pre-school aged children. Children
      born in a prospective mother-child cohort in rural Bangladesh were followed up at
      4.5 years of age (n = 577). Arsenic exposure was assessed by concentrations of
      arsenic metabolites (U-As) in child urine and maternal urine during pregnancy,
      using high-performance liquid chromatography online with inductively coupled
      plasma mass spectrometry. For assessment of delayed type hypersensitivity
      response, an intradermal injection of purified protein derivative (PPD) was given
      to Bacillus Calmette-Guerin vaccinated children. The diameter (mm) of induration
      was measured after 48-72 h. Plasma concentrations of 27 cytokines were analyzed
      by a multiplex cytokine assay. Children's concurrent, but not prenatal, arsenic
      exposure was associated with a weaker response to the injected PPD. The risk
      ratio (RR) of not responding to PPD (induration <5 mm) was 1.37 (95% confidence
      interval (CI): 1.07, 1.74) in children in the highest quartile of U-As (range 126
      1228 MUg/l), compared with the lowest (range 12-34 MUg/l). The p for trend across
      the quartiles was 0.003. The association was stronger in undernourished children.
      Children's U-As in tertiles was inversely associated with two out of 27 cytokines
      only, i.e., IL-2 and TNF-alpha, both Th1 cytokines (in the highest tertile,
      regression coefficients (95% CI): -1.57 (-2.56, -0.57) and -4.53 (-8.62, -0.42),
      respectively), but not with Th2 cytokines. These associations were particularly
      strong in children with recent infections. In conclusion, elevated childhood
      arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to
      reduced concentrations of Th1 cytokines. 

PMID- 24924403
TI  - Social class mobility in first episode psychosis and the association with
      depression, hopelessness and suicidality.
AB  - BACKGROUND: Psychotic disorders are associated with a significant impairment in
      occupational functioning that can begin in the prodromal phase of the disorder.
      As a result, individuals with a psychotic disorder may not maintain their social
      class at birth. The aim of this study was to examine the distribution of the
      social classes of individuals presenting with a first episode of psychosis (FEP)
      compared to the general population and to their family of origin. We evaluated
      whether social drift was associated with depression, hopelessness and suicidality
      at first presentation. METHODS: All individuals with a FEP presenting to a
      community mental health service between 1995 and 1999 and to an early
      intervention service between 2005 and 2011were included. Diagnosis was
      established using the Structured Clinical Interview for DSM IV diagnoses and
      clinical evaluations included the Calgary Depression Scale for Schizophrenia,
      Beck Hopelessness Scale and the Suicidal Intent Scale. RESULTS: 330 individuals
      were included in the study and by the time of presentation, individuals with a
      FEP were more likely to be represented in the lower social classes compared to
      the general population. 43% experienced a social drift and this was associated
      with a diagnosis of a non-affective disorder, co-morbid cannabis abuse and a
      longer DUP. Individuals who did not experience a social drift had a higher risk
      of hopelessness. CONCLUSIONS: Social drift is common in psychotic disorders;
      however, individuals who either maintain their social class or experience upward
      social class mobility are more susceptible to hopelessness.

PMID- 24924405
TI  - The role of dysfunctional attitudes in models of negative symptoms and
      functioning in schizophrenia.
AB  - Neurocognitive impairment is associated with negative symptoms and poor real
      world functioning in schizophrenia. Dysfunctional attitudes (e.g., "If I fail
      partly, it is as bad as being a complete failure") have been found to mediate
      these relationships between neurocognition and negative symptoms and functioning.
      In this study, these relationships were examined in 179 participants with
      schizophrenia or schizoaffective disorder using structural equation modeling.
      Defeatist attitudes were found to mediate the relationship between neurocognition
      and negative symptoms but not the relationships between neurocognition and
      performance-based or self-reported functioning. A full model with the best fit
      showed mediation between neurocognition and self-reported functioning through two
      different pathways: One from neurocognition to functional skill capacity to real
      world functioning, and a second from neurocognition to defeatist attitudes to
      negative symptoms to real-world functioning. These results may implicate skill
      deficits and defeatist attitudes as a separate treatment targets for negative
      symptoms and functioning in schizophrenia. 

PMID- 24924404
TI  - Frequency and pattern of childhood symptom onset reported by first episode
      schizophrenia and clinical high risk youth.
AB  - BACKGROUND: Psychosis prevention and early intervention efforts in schizophrenia
      have focused increasingly on sub-threshold psychotic symptoms in adolescents and
      young adults. Although many youth report symptom onset prior to adolescence, the
      childhood incidence of prodromal-level symptoms in those with schizophrenia or
      related psychoses is largely unknown. METHODS: This study reports on the
      retrospective recall of prodromal-level symptoms from 40 participants in a first
      episode of schizophrenia (FES) and 40 participants at "clinical high risk" (CHR)
      for psychosis. Onset of positive and non-specific symptoms was captured using the
      Structured Interview for Prodromal Syndromes. Frequencies are reported according
      to onset during childhood (prior to age 13), adolescence (13-17), or adulthood
      (18+). RESULTS: Childhood-onset of attenuated psychotic symptoms was not rare. At
      least 11% of FES and 23% of CHR reported specific recall of childhood-onset of
      unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most
      recalled experiencing non-specific symptoms prior to positive symptoms. CHR and
      FES did not differ significantly in the timing of positive and non-specific
      symptom onset. Other than being younger at assessment, those with childhood onset
      did not differ demographically from those with later onset. CONCLUSION: Childhood
      onset of initial psychotic-like symptoms may be more common than previous
      research has suggested. Improved characterization of these symptoms and a focus
      on their predictive value for subsequent schizophrenia and other major psychoses
      are needed to facilitate screening of children presenting with attenuated
      psychotic symptoms. Accurate detection of prodromal symptoms in children might
      facilitate even earlier intervention and the potential to alter pre-illness
      trajectories.

PMID- 24924406
TI  - Investigating facial affect processing in psychosis: a study using the
      Comprehensive Affective Testing System.
AB  - Facial affect processing (FAP) deficits in schizophrenia (SZ) and bipolar
      disorder (BD) have been widely reported; although effect sizes vary across
      studies, and there are limited direct comparisons of the two groups. Further,
      there is debate as to the influence of both psychotic and mood symptoms on FAP.
      This study aimed to address these limitations by recruiting groups of psychosis
      patients with either a diagnosis of SZ or BD and comparing them to healthy
      controls (HC) on a well validated battery of four FAP subtests: affect
      discrimination, name affect, select affect and match affect. Overall, both groups
      performed more poorly than controls in terms of accuracy. In SZ, this was largely
      driven by impairments on three of the four subtests. The BD patients showed
      impaired performance specifically on the match affect subtest, a task that had a
      high cognitive load. FAP performance in the psychosis patients was correlated
      with severity of positive symptoms and mania. This study confirmed that FAP
      deficits are a consistent finding in SZ that occur independent of task specific
      methodology; whilst FAP deficits in BD are more subtle. Further work in this
      group is needed to replicate these results. 

PMID- 24924407
TI  - Self-reported cannabis use is inconsistent with the results from drug-screening
      in youth at ultra high-risk for psychosis in Colorado.

PMID- 24924408
TI  - Hippocampus age-related microstructural changes in schizophrenia: a case-control
      mean diffusivity study.
AB  - Macrostructural-volumetric abnormalities of the hippocampus have been described
      in schizophrenia. Here, we characterized age-related changes of hippocampal mean
      diffusivity as an index of microstructural damage by carrying out a neuroimaging
      study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and
      gender-matched healthy controls. We performed analyses of covariance, with
      diagnosis as fixed factor, mean diffusivity as dependent variable and age as
      covariate. Patients showed an early increase in mean diffusivity in the right and
      left hippocampus that increased with age. Thus, microstructural hippocampal
      changes associated with schizophrenia cannot be confined to a specific time
      window. 

PMID- 24924409
TI  - Functional role of protease activated receptors in vascular biology.
AB  - Protease activated receptors (PARs) are a small family of G protein-coupled
      receptors (GPCR) mediating the cellular effects of some proteases of the
      coagulation system, such as thrombin, or other proteases, such as trypsin or
      metalloproteinase 1. As the prototype of PARs, PAR1 is a seven transmembrane GPCR
      that, upon cleavage by thrombin, unmasks a new amino-terminus able to bind
      intramolecularly to PAR1 itself thus inducing signaling. In the vascular system,
      thrombin and other proteases of the coagulation-fibrinolysis system, such as
      plasmin, factor VIIa and factor Xa, activated protein C, are considered
      physiologically relevant agonists, and PARs appear to largely account for the
      cellular effects of these enzymes. In the vasculature, PARs are expressed on
      platelets, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). In
      the vessel wall, under physiological conditions, PARs are mainly expressed in ECs
      and participate in the regulation of vascular tone, by inducing endothelium
      dependent relaxation. PAR activation on ECs promotes conversion of these cells
      into a proinflammatory phenotype, causes increase of vascular permeability, and
      the exposure/secretion of proteins and cytokines mediating the local accumulation
      of platelets and leukocytes. These effects contribute to the vascular
      consequences of sepsis and of diseases such as acute lung injury and acute
      respiratory distress syndrome. In normal arteries PARs are to a much lesser
      amount expressed on VSMCs. However, in conditions associated with endothelial
      dysfunction, PARs mediate contraction, proliferation, migration, hypertrophy of
      VSMCs and their production of extracellular matrix, thereby contributing to the
      pathophysiology of atherosclerosis and hypertension. Inhibition of protease-PAR
      interaction might thus become a potential therapeutic target in various vascular
      diseases. 

PMID- 24924410
TI  - PCSK9 inhibition for the treatment of hypercholesterolemia: promises and emerging
      challenges.
AB  - Hypercholesterolemia, is a prominent risk factor for cardiovascular disease
      (CVD). Undestanding of the biochemical mechanisms that regulate the expression of
      the low density lipoproteins receptor (LDLR) and the hepatic clearance of LDL
      cholesterol (LDL-C) paved the way to the statin therapy as the gold standard for
      CVD prevention. The discovery of proteins that regulate - at a post-translational
      level - the activity of the LDLR has been a major breakthrough in developing new
      cholesterol-lowering drugs. Proprotein convertase subtilisin/kexin type 9 (PCSK9)
      is a key modulator of the LDLR degradation in the liver. Genetic studies
      confirmed that in humans PCSK9 mutations associate with hypercholesterolemia and
      hypocholesterolemia (gain-of-function or loss-of-function variants respectively).
      Moreover, PCSK9 is up-regulated by statin treatment and limits the efficacy of
      these agents. These findings led to the development of PCSK9 inhibitors. Anti
      PCSK9 monoclonal antibodies showed encouraging results and are currently being
      evaluated in phase III clinical trials. The aim of this short review is to
      describe the new frontier of PCSK9 inhibition in the treatment of
      hypercholesterolemia. Emphasis here is given to critical emerging issues linked
      to PCSK9 physiology and pharmacology, which will require future investigation to
      definitely address the potential of anti-PCSK9 drugs in clinical practice. 

PMID- 24924411
TI  - Remote-controlled drug release from graphene oxide-capped mesoporous silica to
      cancer cells by photoinduced pH-jump activation.
AB  - Remote light control of drug release enhances our ability to address the
      complexity of biological systems because of its remarkable spatial/temporal
      resolution. Here, a new class of remote-controlled release system by
      incorporating photoacid generator (PAG) into graphene oxide-capped mesoporous
      silica was designed for delivering drug payloads to cancer cells via photoinduced
      pH-jump activation. PAG was immobilized on pore wall of the boronic acid-grafted
      mesoporous silica via strong physical adsorption, and then the nanoparticle was
      capped with graphene oxide sheet by an acid-labile boroester bond, leading to the
      formation of nanogated ensemble (MSP-BA-GO). Illuminating with a UV light, PAG
      generated a pH jump, which induced cleavage of the boroester linkers and thus
      resulted in the uncapping of pore gates. Moreover, folic acid-modified,
      doxorubicin (DOX)-loaded MSP-BA-GO (DOX@MSP-BA-GOF) showed selective cell
      internalization via receptor-mediated endocytosis and subsequent released DOX by
      the remote illumination. We envisioned that this remote-controlled drug delivery
      system could find potential applications for cancer therapy. 

PMID- 24924412
TI  - A clinical study of pingyangmycin sclerotherapy for venous malformation: an
      evaluation of 281 consecutive patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: In China, lidocaine together with 2 mg/mL of
      pingyangmycin (PYM, also known as bleomycin A5) is recommended for the treatment
      of venous malformations (VMs). The purpose of this study was to investigate
      whether lidocaine has a synergistic effect with PYM in improving the therapeutic
      outcomes of patients with VMs. Additionally, this study aimed to evaluate the
      outcomes of sclerotherapy for VMs using an intralesional injection of a low
      concentration of PYM (0.5 mg/mL). METHODS: A total of 281 patients with VMs were
      treated with 0.5 or 2 mg/mL of PYM with or without lidocaine and dexamethasone
      (DEX). All of the patients received a direct intralesional injection at a rate of
      1 mL/min, and the volume of the solution varied from 1.5 to 6.0 mL per injection.
      RESULTS AND DISCUSSION: No significant differences were observed in the clinical
      outcomes between the PYM and PYM + lidocaine treatment groups (P > 0.05). The
      clinical outcomes were similar between the groups that were treated with 0.5 and
      2 mg/mL of PYM, but the swelling and pain in the patients who were treated with
      0.5 mg/mL of PYM were less severe compared with the patients who were treated
      with 2 mg/mL of PYM. A total of 29 patients with VM lesions on the glans penis
      were treated with 0.5 mg/mL of PYM + 0.5% lidocaine. Of these patients, 26 were
      cured, whereas three experienced a marked improvement. WHAT IS NEW AND
      CONCLUSION: Lidocaine does not have a synergistic effect with PYM in improving
      the therapeutic outcomes of patients with VMs. Sclerotherapy with a low
      concentration of PYM (0.5 mg/mL) combined with lidocaine and DEX is a safe and
      effective therapy for small superficial VMs of critical organs, such as the lips
      and the glans penis.

PMID- 24924413
TI  - Understanding heterogeneity among elderly consumers: an evaluation of
      segmentation approaches in the functional food market.
AB  - It is beneficial for both the public health community and the food industry to
      meet nutritional needs of elderly consumers through product formats that they
      want. The heterogeneity of the elderly market poses a challenge, however, and
      calls for market segmentation. Although many researchers have proposed ways to
      segment the elderly consumer population, the elderly food market has received
      surprisingly little attention in this respect. Therefore, the present paper
      reviewed eight potential segmentation bases on their appropriateness in the
      context of functional foods aimed at the elderly: cognitive age, life course,
      time perspective, demographics, general food beliefs, food choice motives,
      product attributes and benefits sought, and past purchase. Each of the
      segmentation bases had strengths as well as weaknesses regarding seven evaluation
      criteria. Given that both product design and communication are useful tools to
      increase the appeal of functional foods, we argue that elderly consumers in this
      market may best be segmented using a preference-based segmentation base that is
      predictive of behaviour (for example, attributes and benefits sought), combined
      with a characteristics-based segmentation base that describes consumer
      characteristics (for example, demographics). In the end, the effectiveness of
      (combinations of) segmentation bases for elderly consumers in the functional food
      market remains an empirical matter. We hope that the present review stimulates
      further empirical research that substantiates the ideas presented in this paper. 

PMID- 24924414
TI  - miR-204 suppresses cochlear spiral ganglion neuron survival in vitro by targeting
      TMPRSS3.
AB  - Sensorineural hearing loss (SNHL) is the most common cause of hearing impairment.
      One of the essential steps to prevent progressive hearing loss is to protect
      spiral ganglion neurons (SGNs) from ongoing degeneration. MicroRNAs and TMPRSS3
      (transmembrane protease, serine 3) have been reported to be involved in
      development of SGNs and genesis of SNHL. The aim of this study was to investigate
      the role of miR-204 and TMPRSS3 in SGNs. Effect of miR-204 on cell viability of
      SGNs was first examined using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl
      tetrazolium bromide) assay. Expression of TMPRSS3 in SGNs with or without
      addition of miR-204 was assessed by real-time PCR and western blot further. A
      luciferase reporter activity assay was conducted to confirm target association
      between miR-204 and 3'-UTR of TMPRSS3. Finally, role of TMPRSS3 on cell viability
      of SGNs was evaluated by transfection of TMPRSS3 siRNA. Cell viability of SGNs
      was suppressed by miR-204 in a concentration-dependent manner. Overexpression of
      miR-204 reduced expression of TMPRSS3 in SGNs at both mRNA and protein levels.
      Binding to the 3'-UTR of TMPRSS3 by miR-204 was identified by luciferase assay.
      Knockdown of TMPRSS3 by siRNA significantly inhibits cell viability of SGNs. miR
      204 could be a potential therapeutic target in sensorineural hearing loss. 

PMID- 24924415
TI  - Inhibition of histone demethylase, LSD2 (KDM1B), attenuates DNA methylation and
      increases sensitivity to DNMT inhibitor-induced apoptosis in breast cancer cells.
AB  - Increasing evidence suggests that dysfunction of histone lysine demethylase is
      associated with abnormal chromatin remodeling and gene silencing, contributing to
      breast tumorigenesis. In silico analysis shows that the newly identified histone
      demethylase lysine-specific demethylase 2 is highly expressed in breast cancer,
      especially in invasive tumors. However, it is currently unknown how LSD2
      regulates chromatin remodeling and gene expression regulation in breast cancer.
      Using short hairpin RNA, we stably knocked down LSD2 (LSD2-KD) in MDA-MB-231
      breast cancer cells. LSD2-KD led to accumulation of H3K4me1/2 without changing
      methylation levels of other key histone lysine residues, suggesting that LSD2
      acts as a bona fide H3K4 demethylase in breast cancer cells. LSD2-KD resulted in
      decreased colony formation and attenuated global DNA methylation in MDA-MB-231
      cells. Additionally, treatment with the DNMT inhibitor, 5-aza-deoxycytidine
      (DAC), synergistically increased mRNA expression of aberrantly silenced genes
      important in breast cancer development, including PR, RARbeta, ERalpha, SFRP1,
      SFRP2, and E-cadherin in LSD2-KD cells. Furthermore, LSD2-KD cells are more
      susceptible to cell death than scramble controls, and combined treatment with
      tranylcypromine, an LSD2 inhibitor, and DAC resulted in synergistic growth
      inhibition of breast cancer cells. DNMT inhibition by DAC in LSD2-KD cells led to
      internucleosomal DNA fragmentation, enhanced PARP cleavage and increased sub-G1
      apoptotic cell population. These results demonstrate an important role for LSD2
      in regulation of DNA methylation and gene silencing in breast cancer, and suggest
      that inhibition of LSD2 in combination with DNA methyltransferase inhibition
      represents a novel approach for epigenetic therapy of breast cancer. 

PMID- 24924417
TI  - Valproate and folic acid in pregnancy: associations with autism.

PMID- 24924416
TI  - Randomised, phase II, placebo-controlled, trial of fulvestrant plus vandetanib in
      postmenopausal women with bone only or bone predominant, hormone-receptor
      positive metastatic breast cancer (MBC): the OCOG ZAMBONEY study.
AB  - Biomarkers of bone turnover, including urine N-telopeptide (uNTx), have been used
      as surrogate measures of response to bone-targeted therapies. Vascular
      endothelial growth factor (VEGF) levels correlate with extent of bone metastases.
      We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor
      receptor and RET signalling, improved uNTx response when added to fulvestrant (F)
      in breast cancer patients with bone metastases. Postmenopausal patients with bone
      predominant, hormone-receptor-positive metastatic breast cancer were randomised
      to F (500 mg IM days 1, 15, 29, then monthly) with either vandetanib (100 mg PO
      OD) (FV) or placebo (FP). The primary objective was uNTx response. Secondary
      objectives included PFS, OS, RECIST response, pain scores and toxicity. Sixty-one
      patients were allocated to FV and 68 to FP. Out of 127 analyzable patients, an
      uNTx response occurred in 66 % for FV and 54 % for FP (p = 0.21). No difference
      was detected between groups for PFS; HR = 0.95 (95 % CI 0.65-1.38) or OS HR =
      0.69 (95 % CI 0.37-1.31). For the 62 patients with measurable disease, clinical
      benefit rates were 41 and 43 %, respectively (p = 0.47). Serious adverse events
      were similar, 3.3 % for FV versus 5.9 % for FP. Elevated baseline uNTx (>65 nM
      BCE/mmol Cr) was prognostic for PFS, HR = 1.55 (95 % CI 1.04-2.30) and for OS, HR
      = 2.32 (95 % CI 1.25-4.33). The addition of vandetanib to fulvestrant did not
      improve biomarker response, PFS or OS in patients with bone metastases. Baseline
      bone turnover was prognostic for PFS and OS. 

PMID- 24924418
TI  - What is the risk of death or severe harm due to bone cement implantation syndrome
      among patients undergoing hip hemiarthroplasty for fractured neck of femur? A
      patient safety surveillance study.
AB  - OBJECTIVE: To estimate the risk of death or severe harm due to bone cement
      implantation syndrome (BCIS) among patients undergoing hip hemiarthroplasty for
      fractured neck of femur. SETTING: Hospitals providing secondary and tertiary care
      throughout the National Health Service (NHS) in England and Wales. PARTICIPANTS:
      Cases reported to the National Reporting and Learning System (NRLS) in which the
      reporter clearly describes severe acute patient deterioration associated with
      cement use in hip hemiarthroplasty for fractured neck of femur (assessed
      independently by two reviewers). OUTCOME MEASURES: Primary-number of reported
      deaths, cardiac arrests and periarrests per year. Secondary-timing of
      deterioration and outcome in relation to cement insertion. RESULTS: Between 2005
      and 2012, the NRLS received 62 reports that clearly describe death or severe harm
      associated with the use of cement in hip hemiarthroplasty for fractured neck of
      femur. There was one such incident for every 2900 hemiarthroplasties for
      fractured neck of femur during the period. Of the 62 reports, 41 patients died,
      14 were resuscitated from cardiac arrest and 7 from periarrest. Most reports
      (55/62, 89%) describe acute deterioration occurring during or within a few
      minutes of cement insertion. The vast majority of deaths (33/41, 80%) occurred on
      the operating table. CONCLUSIONS: These reports provide narrative evidence from
      England and Wales that cement use in hip hemiarthroplasty for fractured neck of
      femur is associated with instances of perioperative death or severe harm
      consistent with BCIS. In 2009, the National Patient Safety Agency publicised this
      issue and encouraged the use of mitigation measures. Three-quarters of the deaths
      in this study have occurred since that alert, suggesting incomplete
      implementation or effectiveness of those mitigation measures. There is a need for
      stronger evidence that weighs the risks and benefits of cement in hip
      hemiarthroplasty for fractured neck of femur.

PMID- 24924419
TI  - Modular synthesis of cyclic cis- and trans-1,2-diamine derivatives.
AB  - Structurally diverse carbocycles with two vicinal nitrogen-substituents were
      prepared in expedient three-component reactions from simple amines, aldehydes,
      and nitroalkenes. trans,trans-6-Nitrocyclohex-2-enyl amines were obtained in a
      one-pot domino reaction involving condensation, tautomerisation, conjugate
      addition, and nitro-Mannich cyclisation. Upon employment of less nucleophilic
      carboxamides, a concerted Diels-Alder cycloaddition mechanism operated to give
      the corresponding cis,trans-nitrocyclohexenyl amides. Both types of substituted
      carbocycles offer ample opportunities for chemical manipulations at the core and
      periphery. Ring oxidation with MnO2 affords substituted nitroarenes. Reduction
      with Zn/HCl provides access to various trans- and cis-diaminocyclohexenes,
      respectively, in a straight-forward manner. With enantiopure secondary amines, a
      two-step synthesis of chiral nitrocyclohexadienes was developed (82-94% ee). 

PMID- 24924420
TI  - Pure laparoscopic and robot-assisted laparoscopic reconstructive surgery in
      congenital megaureter: a single institution experience.
AB  - To report our experience of pure laparoscopic and robot-assisted laparoscopic
      reconstructive surgery in congenital megaureter, seven patients (one bilateral)
      with symptomatic congenital megaureter underwent pure laparoscopic or robot
      assisted laparoscopic surgery. The megaureter was exposed at the level of the
      blood vessel and was isolated to the bladder narrow area. Extreme ureter trim and
      submucosal tunnel encapsulation or papillary implantations and anti-reflux ureter
      bladder anastomosis were performed intraperitoneally by pure laparoscopic or
      robot-assisted laparoscopic surgery. The clinical data of seven patients after
      operation were analyzed, including the operation time, intraoperative
      complications, intraoperative bleeding volumes, postoperative complications,
      postoperative hospitalization time and pathological results. All of the patients
      were followed. The operation was successfully performed in seven patients. The
      mean operation times for pure laparoscopic surgery and robotic-assistant
      laparoscopic surgery were 175 (range: 150-220) and 187 (range: 170-205) min,
      respectively, and the mean operative blood loss volumes were 20 (range: 10-30)
      and 28.75 (range: 15-20) ml, respectively. There were no intraoperative
      complications. The postoperative drainage time was 5 (range: 4-6) and 5.75
      (range: 5-6) d, respectively, and the indwelling catheter time was 6.33 (range: 4
      8) d and 7 (range: 7-7) d, respectively. The postoperative hospitalization time
      was 7.67 (range: 7-8) d and 8 (range: 7-10) d, respectively. There was no obvious
      pain, no secondary bleeding and no urine leakage after the operation.
      Postoperative pathology reports revealed chronic urothelial mucosa inflammation.
      The follow-up results confirmed that all patients were relieved of their
      symptoms. Both pure laparoscopic and robot-assisted laparoscopic surgery using
      different anti-reflux ureter bladder anastomoses are safe and effective
      approaches in the minimally invasive treatment of congenital megaureter. 

PMID- 24924422
TI  - Heterogeneity in the effect of public health insurance on catastrophic out-of
      pocket health expenditures: the case of Mexico.
AB  - Low- and middle-income countries increasingly provide broad-based public health
      coverage to their residents. One of the goals of such programmes is to reduce the
      extent to which beneficiaries incur catastrophic out-of-pocket expenditures on
      health care. A recent field experiment showed that on average Mexico's new public
      insurance programme reduced such expenditures in rural areas. Our reanalysis of
      that data, augmented with administrative data on health infrastructure, shows
      that this effect depends strongly on the type of health facility to which the
      beneficiary has access. A second analysis, based on data from Mexico's National
      Household Income and Expenditure Surveys (abbreviated ENIGH for its name in
      Spanish), substantiates those findings. It shows that catastrophic expenditures
      have fallen sharply for rural households with access to well-staffed facilities,
      but that they have fallen little if at all for rural households with access to
      poorly staffed facilities. Our analysis of the ENIGH also shows that Mexico's
      public health insurance programme has sharply reduced catastrophic spending among
      urban households. Considering that most Mexicans live either in urban areas or in
      rural areas with access to well-staffed facilities, our results show that the
      public health insurance programme has been largely successful in achieving one of
      its key goals. At the same time, our results show how difficult it can be to
      provide effective protection against catastrophic health expenditures for
      residents of remote rural areas. 

PMID- 24924421
TI  - The effect of wheat prebiotics on the gut bacterial population and iron status of
      iron deficient broiler chickens.
AB  - BACKGROUND: Currently, there is a lot of interest in improving gut health, and
      consequently increasing Fe absorption, by managing the colonic microbial
      population. This is traditionally done by the consumption of probiotics, live
      microbial food supplements. However, an alternative, and often very effective
      approach, is the consumption of food ingredients known as prebiotics. Fructans
      and arabinoxylans are naturally occurring non-digestible oligosaccharides in
      wheat that exhibit prebiotic properties and may enhance intestinal iron (Fe)
      absorption. The aim of this study was to assess the effect of prebiotics from
      wheat on Fe bioavailability in vitro (Caco-2 cells) and in vivo (broiler
      chickens, Gallus gallus). METHODS: In the current study, the effect of intra
      amniotic administration of wheat samples extracts at 17 d of embryonic incubation
      on the Fe status and possible changes in the bacterial population in intestinal
      content of broiler hatchlings were investigated. A group of 144 eggs were
      injected with the specified solution (1 ml per egg) into the amniotic fluid.
      Immediately after hatch (21 d) and from each treatment group, 10 chicks were
      euthanized and their small intestine, liver and cecum were removed for relative
      mRNA abundance of intestinal Fe related transporters, relative liver ferritin
      amounts and bacterial analysis of cecal content, respectively. RESULTS: The in
      vivo results are in agreement with the in vitro observations, showing no
      differences in the hatchling Fe status between the treatment groups, as Fe
      bioavailability was not increased in vitro and no significant differences were
      measured in the intestinal expression of DMT1, Ferroportin and DcytB in vivo.
      However, there was significant variation in relative amounts of bifidobacteria
      and lactobacilli in the intestinal content between the treatments groups, with
      generally more bifidobacteria being produced with increased prebiotic content.
      CONCLUSIONS: In this study we showed that prebiotics naturally found in wheat
      grains/bread products significantly increased intestinal beneficial bacterial
      population in Fe deficient broiler chickens. With this short-term feeding trial
      we were not able to show differences in the Fe-status of broilers. Nevertheless,
      the increase in relative amounts of bifidobacteria and lactobacilli in the
      presence of wheat prebiotics is an important finding as these bacterial
      populations may affect Fe bioavailability in long-term studies.

PMID- 24924423
TI  - Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase
      isozymes.
AB  - Oxo-lipids, a large family of oxidized human lipoxygenase (hLOX) products, are of
      increasing interest to researchers due to their involvement in different
      inflammatory responses in the cell. Oxo-lipids are unique because they contain
      electrophilic sites that can potentially form covalent bonds through a Michael
      addition mechanism with nucleophilic residues in protein active sites and thus
      increase inhibitor potency. Due to the resemblance of oxo-lipids to LOX
      substrates, the inhibitor potency of 4 different oxo-lipids; 5-oxo-6,8,11,14
      (E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), 15-oxo-5,8,11,13-(Z,Z,Z,E)
      eicosatetraenoic acid (15-oxo-ETE), 12-oxo-5,8,10,14-(Z,Z,E,Z)-eicosatetraenoic
      acid (12-oxo-ETE), and 13-oxo-9,11-(Z,E)-octadecadienoic acid (13-oxo-ODE) were
      determined against a library of LOX isozymes; leukocyte 5-lipoxygenase (h5-LOX),
      human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), human platelet 12-lipoxygenase
      (h12-LOX), human epithelial 15-lipoxygenase-2 (h15-LOX-2), soybean 15
      lipoxygenase-1 (s15-LOX-1), and rabbit reticulocyte 15-LOX (r15-LOX). 15-Oxo-ETE
      exhibited the highest potency against h12-LOX, with an IC50=1 +/- 0.1 MUM and was
      highly selective. Steady state inhibition kinetic experiments determined 15-oxo
      ETE to be a mixed inhibitor against h12-LOX, with a Kic value of 0.087 +/- 0.008
      MUM and a Kiu value of 2.10 +/- 0.8 MUM. Time-dependent studies demonstrated
      irreversible inhibition with 12-oxo-ETE and h15-LOX-1, however, the concentration
      of 12-oxo-ETE required (Ki=36.8 +/- 13.2 MUM) and the time frame (k2=0.0019 +/-
      0.00032 s(-1)) were not biologically relevant. These data are the first
      observations that oxo-lipids can inhibit LOX isozymes and may be another
      mechanism in which LOX products regulate LOX activity.

PMID- 24924424
TI  - Facile synthesis, optical and conformational characteristics, and efficient
      intracellular delivery of a peptide-DNA conjugate.
AB  - Covalent conjugation of disparate peptide and oligonucleotide biomacromolecular
      species produces peptide-oligonucleotide conjugates (POCs), which are interesting
      molecules with great potential for use in diverse bioapplications. However,
      peptide-oligonucleotide conjugation methods are not well established, and the
      intracellular delivery efficacy of POCs is debatable. Here, we describe a simple
      method for the synthesis and purification of POCs. When peptides are carefully
      designed to have a near-neutral charge state, a relatively hydrophobic polarity,
      and receptor-targeting ligands, synthesis and purification become highly
      efficient and straightforward. UV-vis, fluorescence, and circular dichroism
      studies show that both types of molecules mutually influence each other, changing
      their optical and conformational characteristics in the context of POCs. The
      combined effect of peptide design strategy, targeting ligands, and relatively
      hydrophobic property, enables the efficient cellular delivery of POCs. 

PMID- 24924425
TI  - Synthesis, antioxidant and cytoprotective evaluation of potential antiatherogenic
      phenolic hydrazones. A structure-activity relationship insight.
AB  - A novel series of hydrazones derived from substituted benzaldehydes have been
      synthesized as potential antiatherogenic agents. Several methods were used for
      exploring their antioxidant and cytoprotective properties, such as their
      scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, the inhibition
      of superoxide anion (O2(.-)) generation and the measurement of cell-induced low
      density lipoprotein oxidation (monitored by the formation of TBARS). The
      cytoprotective efficacy was also evaluated by measuring the cell viability
      (monitored by the MTT assay) in the presence of cytotoxic oxidized LDL. In this
      report, we discuss the relationship between the chemical structure of phenolic
      hydrazones and their antioxidant and cytoprotective activities, for subsequent
      application as antiatherogenic agents. This SAR study confirms that the phenolic
      frame is not the only prerequisite for antioxidant activity and N
      methylbenzothiazole hydrazone moiety magnifies the dual required properties in
      two most interesting derivatives.

PMID- 24924426
TI  - Matching Patterns of Gene Expression to Mechanical Stiffness at Cell Resolution
      through Quantitative Tandem Epifluorescence and Nanoindentation.
AB  - Cell differentiation has been associated with changes in mechanical stiffness in
      single-cell systems, yet it is unknown whether this association remains true in a
      multicellular context, particularly in developing tissues. In order to address
      such questions, we have developed a methodology, termed quantitative tandem
      epifluorescence and nanoindentation, wherein we sequentially determine cellular
      genetic identity with confocal microscopy and mechanical properties with atomic
      force microscopy. We have applied this approach to examine cellular stiffness at
      the shoot apices of Arabidopsis (Arabidopsis thaliana) plants carrying a
      fluorescent reporter for the CLAVATA3 (CLV3) gene, which encodes a secreted
      glycopeptide involved in the regulation of the centrally located stem cell zone
      in inflorescence and floral meristems. We found that these CLV3-expressing cells
      are characterized by an enhanced stiffness. Additionally, by tracking cells in
      young flowers before and after the onset of GREEN FLUORESCENT PROTEIN expression,
      we observed that an increase in stiffness coincides with this onset. This work
      illustrates how quantitative tandem epifluorescence and nanoindentation can
      reveal the spatial and temporal dynamics of both gene expression and cell
      mechanics at the shoot apex and, by extension, in the epidermis of any thick
      tissue.

PMID- 24924427
TI  - Effects of interface pressure distribution on human sleep quality.
AB  - High sleep quality promotes efficient performance in the following day. Sleep
      quality is influenced by environmental factors, such as temperature, light, sound
      and smell. Here, we investigated whether differences in the interface pressure
      distribution on healthy individuals during sleep influenced sleep quality. We
      defined four types of pressure models by differences in the area distribution and
      the subjective feelings that occurred when participants slept on the mattresses.
      One type of model was showed "over-concentrated" distribution of pressure; one
      was displayed "over-evenly" distributed interface pressure while the other two
      models were displayed intermediate distribution of pressure. A polysomnography
      analysis demonstrated an increase in duration and proportion of non-rapid-eye
      movement sleep stages 3 and 4, as well as decreased number of micro-arousals, in
      subjects sleeping on models with pressure intermediately distributed compared to
      models with over-concentrated or over-even distribution of pressure. Similarly,
      higher scores of self-reported sleep quality were obtained in subjects sleeping
      on the two models with intermediate pressure distribution. Thus, pressure
      distribution, at least to some degree, influences sleep quality and self-reported
      feelings of sleep-related events, though the underlying mechanisms remain
      unknown. The regulation of pressure models imposed by external sleep environment
      may be a new direction for improving sleep quality. Only an appropriate interface
      pressure distribution is beneficial for improving sleep quality, over
      concentrated or -even distribution of pressure do not help for good sleep. 

PMID- 24924429
TI  - Sensation seeking and error processing.
AB  - Sensation seeking is defined by a strong need for varied, novel, complex, and
      intense stimulation, and a willingness to take risks for such experience. Several
      theories propose that the insensitivity to negative consequences incurred by
      risks is one of the hallmarks of sensation-seeking behaviors. In this study, we
      investigated the time course of error processing in sensation seeking by
      recording event-related potentials (ERPs) while high and low sensation seekers
      performed an Eriksen flanker task. Whereas there were no group differences in
      ERPs to correct trials, sensation seeking was associated with a blunted error
      related negativity (ERN), which was female-specific. Further, different
      subdimensions of sensation seeking were related to ERN amplitude differently.
      These findings indicate that the relationship between sensation seeking and error
      processing is sex-specific. 

PMID- 24924428
TI  - Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis
      through M2-type macrophages.
AB  - Tumors formed by a highly metastatic human lung cancer cell line are
      characterized by activated signaling via vascular endothelial growth factor
      (VEGF)-C through its receptor (VEGFR-3) and aggressive lymph node metastasis. In
      this study, we examined how these highly metastatic cancers acquired aggressive
      lymph node metastasis. Compared with their lower metastatic counterparts, the
      highly metastatic tumors formed by this cell line expressed higher amounts of
      interleukin (IL)-1alpha, with similarly augmented expression of IL-1alpha and IL
      1beta by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated
      macrophages. These tumor-associated macrophages were mainly of the M2 type.
      Administration of a macrophage-targeting drug suppressed the production of these
      potent angiogenic and lymphangiogenic factors, resulting in decreased tumor
      growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel
      plug assays, the highly metastatic cells formed tumors that were extensively
      infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and
      lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor
      (IL-1R) antagonist anakinra. Thus, the IL-1alpha-driven inflammatory activation
      of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor
      microenvironment favorable for lymph node metastasis through cross-talk with
      macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good
      therapeutic target for patients with this form of lung cancer. 

PMID- 24924431
TI  - Access to and utilization of the health services among the patients in a
      government homeopathic hospital in West Bengal, India: a cross-sectional study.
AB  - Accessibility to and utilization of the hospital health services is a complex and
      multifaceted issue. This study aimed to assess the knowledge of the patients of
      health services, current level of access to and utilization of services and to
      identify barriers and socioeconomic disparities in an Indian homeopathic
      hospital. A cross-sectional survey was conducted in December 2013 on
      systematically sampled 377 patients. Responses were analyzed using descriptive
      statistics and univariate logistic regression. Mean knowledge score and perceived
      mean difficulties in access to and utilization of services were 68.4% and 78.5%,
      respectively. Knowledge of the services was influenced by age, residence,
      education, speaking and reading of Bengali language, and income status (P < .05).
      Difficulty in access to and utilization of the health services were influenced by
      residence, understanding of Bengali language, and monthly household income (P <
      .05). Overall, health service access and utilization appeared promising, but
      needs improvement. 

PMID- 24924430
TI  - Introduction of the human AVPR1A gene substantially alters brain receptor
      expression patterns and enhances aspects of social behavior in transgenic mice.
AB  - Central arginine vasopressin receptor 1A (AVPR1A) modulates a wide range of
      behaviors, including stress management and territorial aggression, as well as
      social bonding and recognition. Inter- and intra-species variations in the
      expression pattern of AVPR1A in the brain and downstream differential behavioral
      phenotypes have been attributed to differences in the non-coding regions of the
      AVPR1A gene, including polymorphic elements within upstream regulatory areas.
      Gene association studies have suggested a link between AVPR1A polymorphisms and
      autism, and AVPR1A has emerged as a potential pharmacological target for
      treatment of social cognitive impairments and mood and anxiety disorders. To
      further investigate the genetic mechanism giving rise to species differences in
      AVPR1A expression patterns and associated social behaviors, and to create a
      preclinical mouse model useful for screening drugs targeting AVPR1A, we
      engineered and extensively characterized bacterial artificial chromosome (BAC)
      transgenic mice harboring the entire human AVPR1A locus with the surrounding
      regulatory elements. Compared with wild-type animals, the humanized mice
      displayed a more widely distributed ligand-AVPR1A binding pattern, which
      overlapped with that of primates. Furthermore, humanized AVPR1A mice displayed
      increased reciprocal social interactions compared with wild-type animals, but no
      differences in social approach and preference for social novelty were observed.
      Aspects of learning and memory, specifically novel object recognition and spatial
      relocation recognition, were unaffected. The biological alterations in humanized
      AVPR1A mice resulted in the rescue of the prepulse inhibition impairments that
      were observed in knockout mice, indicating conserved functionality. Although
      further behavioral paradigms and additional cohorts need to be examined in
      humanized AVPR1A mice, the results demonstrate that species-specific variations
      in the genomic content of regulatory regions surrounding the AVPR1A locus are
      responsible for differential receptor protein expression patterns across species
      and that they are likely to contribute to species-specific behavioral variation.
      The humanized AVPR1A mouse is a potential preclinical model for further
      understanding the regulation of receptor gene expression and the impact of
      variation in receptor expression on behaviors, and should be useful for screening
      drugs targeting human AVPR1A, taking advantage of the expression of human AVPR1A
      in human-relevant brain regions. 

PMID- 24924432
TI  - Ultrasound-guided fine needle aspiration cytology of a primary lymph node
      leiomyoma: a flexible procedure for a complex case.
AB  - BACKGROUND: A primary lymph node leiomyoma diagnosed by fine needle aspiration
      cytology (FNAC) is reported. CASE: A 22-year-old male complained of right groin
      swelling; ultrasound examination (US) showed a lymph node containing a 20-mm
      hypoechoic nodule. The residual lymph node was oval, with a well-characterized
      cortex and hilum. US-FNAC of the nodule showed oval spindle cells embedded in
      fibrillar matrix. Nuclei were naked and oval with dispersed chromatin but without
      nucleoli. Immunocytochemistry showed positivity for vimentin and actin, and
      negativity for cytokeratin, S100, CD23 and CD31. A smear of the residual lymph
      node showed a reactive lymphoid cell population. FNAC diagnosis was mesenchymal
      cell proliferation with smooth muscle phenotype; a lymph node is part of the
      lesion. A CT scan did not detect any inguinal or abdominal mass. The surgical
      sample was a lymph node containing a spindle cell tumor, which was actin and
      desmin positive, and S100, CD21, HMB45, CD23 and CD31 negative; MIB1 was positive
      in <5% of the cells. The residual lymph node was normal. CONCLUSION: The final
      diagnosis was primary benign leiomyoma in a lymph node. US-FNAC may frame complex
      lymph node lesions and provide treatment options.

PMID- 24924433
TI  - A 2q24.3q31.1 microdeletion found in a patient with Filippi-like syndrome
      phenotype: a case report.
AB  - Filippi syndrome is characterized by developmental delay, growth failure,
      cryptorchidism, bilateral hand and foot syndactyly, and facial dysmorphism. The
      2q24q31 contiguous deletion syndrome has similarly been associated with hand and
      foot anomalies, growth retardation, microcephaly, characteristic facies with a
      broad prominent nasal root and thin alae nasi, and intellectual disability. We
      present a patient with this deletion who has a Filippi-like phenotype, which may
      be the first causative cytogenetic result in this syndrome. This suggests the
      importance of array comparative genomic hybridization in evaluation of patients
      with Filippi syndrome, and suggests that the inheritance may not always be
      autosomal recessive.

PMID- 24924435
TI  - Dujardinascaris gigantea sp. n. (Nematoda: Ascaridida) from the critically
      endangered crocodile Alligator sinensis Fauvel (Reptilia: Crocodylia).
AB  - The Chinese alligator Alligator sinensis Fauvel (Reptilia: Crocodylia) is
      considered as one of the most critically endangered species of the 23 extant
      crocodiles. However, our knowledge of the helminth parasites of this rare animal
      is completely lacking. During a helminthological survey of reptiles in China, we
      found a new ascaridoid nematode, Dujardinascaris gigantea sp. n. from A.
      sinensis. The morphology of D. gigantea sp. n. was studied using light and
      scanning electron microscopy. The new species was also characterised using
      molecular methods by sequencing and analysing the small ribosomal DNA (18S) and
      the second internal transcribed spacer (ITS-2). 

PMID- 24924434
TI  - Characterisation of the mitochondrial genome of Parafilaroides normani (lungworm)
      of Arctocephalus pusillus doriferus (Australian fur seal).
AB  - Parafilaroides normani is a metastrongyloid nematode of clinical relevance in
      some species of pinnipeds. The taxonomy, biology and epidemiology of this and
      related species are not well understood. Mitochondrial (mt) DNA can provide
      markers for studies in these areas, but genetic data are scant. Here, we
      characterised the mt genome of P. normani. Adults of this nematode were collected
      from Arctocephalus pusillus doriferus from Phillip Island, Victoria, Australia,
      and genomic DNA was extracted from individuals. The complete mt genome was
      amplified from DNA from a single adult male by long-range PCR, as two overlapping
      amplicons (~5 and ~10 kb), and then sequenced employing 454 technology (Roche).
      The mt genome was assembled from reads of ~300 bp and annotated using an
      established bioinformatic pipeline. This circular mt genome is 13,411 bp and
      contains two ribosomal RNA, 12 protein-coding and 22 transfer RNA genes,
      consistent with those of other lungworms studied to date. This mt genome is
      intended to provide a source of genetic markers for future investigations of the
      biology, epidemiology and systematics of Parafilaroides spp. and related
      lungworms.

PMID- 24924436
TI  - Exploring the antigenic features of Fasciola hepatica rediae (Trematoda: Digenea)
      through the evaluation of different antigenic candidates for further monoclonal
      antibody generation.
AB  - The control of fasciolosis, as that of other vector-borne diseases, must be
      related to the control of the lymnaeid snails, the intermediate hosts of the
      parasite. Thus, an accurate epidemiological surveillance of the transmission foci
      where the infected mollusks occur is essential. For this purpose, immunoassays
      could be a useful tool. However, information regarding specific proteins of
      intramolluscan larvae and previous studies concerning monoclonal antibody
      generation against asexual stages of trematodes are scarce. Therefore, we
      explored the antigenic features of intramolluscan rediae of Fasciola hepatica to
      evaluate three antigenic preparations in order to use the most promising one for
      developing specific monoclonal antibodies. Mouse antiserum was generated against
      each antigen for assessing the polyclonal antibody response against the crude
      extract of rediae and the cross-reactivity against lymnaeids. The specific C
      terminal of F. hepatica cytochrome c oxidase subunit I (first antigen), selected
      by in silico analyses, might not be the appropriate target for immunoassay
      detection of infected snails, due to its low representation in the total extract
      of rediae. The majoritarian mixture of low-molecular-weight proteins (<30 kDa)
      from the rediae homogenate (second antigen) revealed a significant cross
      reactivity with lymnaeids. Evidence of the existence of mimetic immunogenic
      epitopes in this fraction of F. hepatica rediae was achieved. High immunogenicity
      of the crude extract of rediae (third antigen), mainly related to parasite's
      specific epitopes, was regarded. Therefore, the rediae homogenate is stated as
      the most promising antigen from those evaluated, for monoclonal antibody
      development with potentialities for detecting F. hepatica-infected snails.

PMID- 24924437
TI  - Proactive approaches to successful aging: one clear path through the forest.
AB  - The importance of successful aging is increasingly acknowledged in the field of
      gerontology. In this paper we contribute to ongoing efforts to clarify and
      operationalize this concept by presenting our revised Comprehensive Preventive
      Corrective Proactive (PCP) model that builds on relevant research traditions, our
      prior formulations and accumulating research evidence based on testing this
      model. Recognizing biopsychosocial challenges and contextual stressors that are
      normative for older individuals, we emphasize the critical role of proactive
      behavioral adaptations in ameliorating the adverse effects of stressors. We argue
      that competent actions to address age-related changes and stressors are necessary
      to achieve positive quality-of-life outcomes. We propose that future research may
      benefit from employing more complex methodological approaches and data analytic
      tools.

PMID- 24924438
TI  - Daily and seasonal dynamics of remotely sensed photosynthetic efficiency in tree
      canopies.
AB  - The photosynthesis of various species or even a single plant varies dramatically
      in time and space, creating great spatial heterogeneity within a plant canopy.
      Continuous and spatially explicit monitoring is, therefore, required to assess
      the dynamic response of plant photosynthesis to the changing environment. This is
      a very challenging task when using the existing portable field instrumentation.
      This paper reports on the application of a technique, laser-induced fluorescence
      transient (LIFT), developed for ground remote measurement of photosynthetic
      efficiency at a distance of up to 50 m. The LIFT technique was used to monitor
      the seasonal dynamics of selected leaf groups within inaccessible canopies of
      deciduous and evergreen tree species. Electron transport rates computed from LIFT
      measurements varied over the growth period between the different species studied.
      The LIFT canopy data and light-use efficiency measured under field conditions
      correlated reasonably well with the single-leaf pulse amplitude-modulated
      measurements of broadleaf species, but differed significantly in the case of
      conifer tree species. The LIFT method has proven to be applicable for a remote
      sensing assessment of photosynthetic parameters on a diurnal and seasonal scale;
      further investigation is, however, needed to evaluate the influence of complex
      heterogeneous canopy structures on LIFT-measured chlorophyll fluorescence
      parameters. 

PMID- 24924439
TI  - Prevalence and causes of visual impairment in diabetic patients in Tunisia, North
      Africa.
AB  - PURPOSE: To investigate the prevalence and causes of blindness and partial sight
      among a population of Tunisian diabetic patients. METHODS: A cross-sectional
      study of 2320 randomly identified patients with diabetes mellitus. Patient's
      characteristics as well as data from the last ophthalmic examination were
      reviewed. RESULTS: Of all patients examined, 60.2% were females and 39.8% were
      males. Mean age of patients was 54.5 years. Mean duration of diabetes was 7.6
      years. Diabetic retinopathy (DR) was recorded in 26.3% of patients, and was
      proliferative in 3.4% of patients. The prevalence of visual impairment was 22.2%,
      with 4.4% patients legally blind and 17.8% partially sighted. Visual impairment
      was significantly associated with age >=60 years (P<0.001), duration of diabetes
      >10 years (P<0.001), body mass index >25 (P=0.014), hypertension (P<0.001), heart
      disease (P<0.001), peripheral neuropathy (P=0.03), vegetative neuropathy
      (P=0.002), macroalbuminuria (P<0.001), cataract (P<0.001), DR (P<0.001), diabetic
      macular edema (P<0.001), open angle glaucoma (P<0.001), intravitreal hemorrhage
      (P<0.001), rubeosis iridis (P<0.001), neovascular glaucoma (P<0.001), and
      tractional retinal detachment (P<0.001). CONCLUSION: The current report is the
      largest study of DR in North African region. It provides a baseline data against
      which future progress can be assessed. Screening and treatment can greatly reduce
      the incidence of visual impairment due to diabetes.

PMID- 24924440
TI  - The noninvasive retro-mode imaging of confocal scanning laser ophthalmoscopy in
      myopic maculopathy: a prospective observational study.
AB  - PURPOSE: To investigate the morphological features of myopic maculopathy with a
      new and noninvasive retro-mode imaging (RMI) technique using a confocal scanning
      laser ophthalmoscope. METHODS: A total of 42 patients (69 eyes) with myopic
      maculopathy were included. RMI combined with fundus photography, fundus
      fluorescein angiography, and optical coherence tomography together were used to
      observe and evaluate the morphological features of disease. RESULTS: Four in 4
      eyes (100%) with macular retinoschisis were found with a characteristic pattern
      by RMI (firework pattern centrally with surrounding fingerprint pattern). Twenty
      four in 24 eyes (100%) with pigment proliferation were found by RMI as dark plain
      patches, and 23 in 24 eyes with hemorrhage (95.8%) were found by RMI as gray
      bump. Atrophy of different degrees (12 in 14 eyes, 85.7%) was found by RMI as an
      area of pseudo-3D choroidal vessels or a fuzzy shadow but both without a clear
      boundary. Choroidal neovascularization (12 in 16 eyes, 75%) was identified
      laboriously by RMI as a vague raised region. Lacquer cracks were difficult to
      figure out in RMI. CONCLUSIONS: Retinoschisis, pigment proliferation, hemorrhage,
      and atrophy secondary to myopic maculopathy have characteristic morphologic
      features in RMI; however, choroidal neovascularization and lacquer crack are not
      easily distinguishable in RMI.

PMID- 24924441
TI  - Melatonin prevents retinal oxidative stress and vascular changes in diabetic
      rats.
AB  - PURPOSE: To evaluate the role of melatonin, an antioxidant agent, in diabetic
      oxidative stress and vascular damage. METHODS: Diabetes was induced in 21 male
      Wistar rats by intraperitoneal (IP) administration of streptozotocin and then the
      rats were equally and randomly allocated to diabetic, melatonin, and vehicle
      groups. Seven healthy normal rats with similar features comprised the control
      group as the fourth group. All animals were followed for 12 weeks. The melatonin
      group received IP melatonin daily and the vehicle group received 2.5% ethanol IP
      at the last month. At the end of 12 weeks, the rats were killed and retinas were
      harvested. The retinas were investigated for the existence of hypoxia-inducible
      factor 1-alpha (HIF-1alpha), vascular endothelial growth factor A (VEGF-A), and
      pigment epithelium-derived factor (PEDF) by ELISA. Retinal oxidative stress is
      quantitated by measuring nitrotyrosine and malondialdehyde levels. Retinal
      immunohistochemistry with antibody against CD31 antigen was carried out on
      retinal cross-sections. For statistics, ANOVA test was used for multiple
      comparisons. RESULTS: Hyperglycemia increased retinal oxidation as measured
      through levels of nitrotyrosine and malondialdehyde. Diabetic retinas are also
      associated with abnormal vascular changes such as dilatation and deformation. HIF
      1alpha, VEGF-A, and PEDF were all increased because of diabetic injury. Melatonin
      showed a potential beneficial effect on retinopathy in diabetic rats. It
      decreased retinal nitrotyrosine and malondialdehyde levels, showing an
      antioxidative support. The vasculomodulator cytokines are decreased accordingly
      by melatonin therapy. Melatonin normalized retinal vascular changes as well.
      CONCLUSION: Melatonin may show some advantage on diabetic vascular changes
      through decreasing oxidative stress and vessel-related cytokines.

PMID- 24924442
TI  - Evaluation of pain during intravitreal Ozurdex injections vs. intravitreal
      bevacizumab injections.
AB  - PURPOSE: The purpose was to evaluate the pain associated with intravitreal
      Ozurdex injections, and to compare it with that associated with intravitreal
      bevacizumab injections. METHODS: The study included 57 eyes of 57 patients who
      received an intravitreal Ozurdex injection at our institution. Pain was measured
      by the visual analog scale (VAS). Additional parameters recorded included age,
      sex, indication for the injection, number of previous Ozurdex injections in the
      study eye, presence of diabetes mellitus, and lens status. Data were compared
      with a 2 : 1 sex- and age-matched control group of 114 patients who received
      intravitreal bevacizumab injections. RESULTS: Indications for injection included
      diabetic macular edema (40.4%) and macular edema secondary to central and branch
      retinal vein occlusion (28% and 31.6%, respectively). Pain scores on the VAS
      ranged from 0 to 90, with a mean of 20.8+/-20.3. There was no significant
      difference in pain between Ozurdex and bevacizumab injections. Pseudophakia was
      correlated with increased pain in Ozurdex injections. CONCLUSIONS: This is the
      first series evaluating the pain associated with intravitreal Ozurdex injections.
      Despite a larger needle gauge and tunneled injection technique, intravitreal
      injection of Ozurdex is not associated with increased pain compared with
      bevacizumab. This finding may be a potential advantage for Ozurdex, and may serve
      to improve patient compliance with future long-term treatment protocols.

PMID- 24924443
TI  - Polypoidal choroidal vasculopathy and history of central serous
      chorioretinopathy.
AB  - PURPOSE: To evaluate the possible causative role of central serous
      chorioretinopathy (CSC) in the development of exudative age-related macular
      degeneration (AMD). METHODS: In a cross-sectional study at an institutional
      setting, 150 control subjects who had senile cataract or nasolacrimal duct
      stenosis and who were older than 50 years were enrolled. The background data for
      89 patients with typical AMD (tAMD) and 138 patients with polypoidal choroidal
      vasculopathy (PCV) were used for comparison. Their medical records were taken for
      history of CSC, hypertension, systemic steroid use, and smoking. The fundus was
      also evaluated for signs of atrophic retinal pigment epithelial (RPE) tract and
      for focal photocoagulation scars in the macula. RESULTS: After adjusting for age,
      gender, and history of hypertension, systemic steroid use, and smoking, history
      of CSC was significantly more frequent (P<0.0001) in patients with PCV (15
      patients, 10.9%) compared with patients with tAMD (2 patients, 2.2%) or control
      subjects (0 patients). On fundoscopy, an atrophic RPE tract (seven patients) or a
      focal photocoagulation scar (one patient) was observed only in patients with PCV
      (eight patients, 5.8%), and the frequency was statistically significant compared
      with that with tAMD (P=0.0143) or control subjects (P=0.0143). The laterality of
      CSC and AMD involved the same eye in 9 of 10 patients among those who had
      unilateral AMD and a reported unilateral CSC history. CONCLUSION: A history of
      CSC may be a predisposing factor for the development of PCV in the Japanese
      population.

PMID- 24924444
TI  - Periocular implantation cysts: a late complication of ophthalmic surgery.
AB  - PURPOSE: To describe the clinical characteristics for a group of patients
      presenting with acquired implantation cysts following periocular surgery.
      METHODS: Retrospective, non-comparative series of patients who underwent surgery
      at Moorfields Eye Hospital for orbital implantation cysts, with review of
      clinical case notes and imaging. RESULTS: Twenty-three patients (13 male; 57%)
      were treated between 1997 and 2011 with cystic lesions that presented at an
      average interval of 22.7 years after previous periocular surgery. The age at
      presentation ranged from 14 to 76 years (mean 45.3; median 46 years). Five
      patients had a history of prior enucleation or evisceration (with ball
      implantation in 4/5 cases) and six had undergone orbital fracture repair with
      either a silicone or titanium plate. Eight patients had prior strabismus surgery,
      three had retinal detachment repair with either a scleral buckle or vitrectomy,
      and one patient had repair of a conjunctival laceration in childhood. All but one
      patient underwent either wide marsupialisation or complete excision of the
      implantation cysts, with no record of recurrence. Visual acuity improved after
      surgery in a half of the patients, whereas remaining unchanged in the remainder.
      CONCLUSION: Orbital implantation cysts constitute a relatively rare complication
      of periocular surgery and can present decades after the causative procedure.

PMID- 24924445
TI  - Visual outcomes of vitrectomy for polypoidal choroidal vasculopathy-related
      breakthrough vitreous haemorrhage.
AB  - PURPOSE: To evaluate the long-term visual outcomes of pars plana vitrectomy (PPV)
      for polypoidal choroidal vasculopathy (PCV)-associated vitreous haemorrhage (VH).
      METHOD: We retrospectively reviewed the records of patients with PCV-related VH
      who underwent PPV. The main outcome measures were best-corrected visual acuity
      (BCVA) and fundus findings at 3 months postoperatively and final visit. RESULTS:
      Seventeen eyes of 17 patients with massive subretinal haemorrhage (16.7+/-7.1
      disc size of mean subretinal haemorrhage area) were enrolled. The mean
      postoperative follow-up period was 25.2 months. Four eyes received intravitreal
      bevacizumab injections, and three eyes underwent photodynamic therapy before the
      onset of VH. The mean BCVA improved from logarithm of the minimum angle of
      resolution (LogMAR) of 2.63+/-0.57 preoperatively to 1.43+/-0.82 at final visit
      (P<0.001). Among the eyes with initial polyps at subfoveal or juxtafoveal area,
      16.70% achieved final BCVA >=20/400 (LogMAR 1.3), whereas 87.50% of eyes with
      initial polyps at extrafoveal area had final BCVA >=20/400 (Fisher's exact test,
      P=0.026). CONCLUSIONS: PCV with massive subretinal haemorrhage is at risk for
      breakthrough VH. The visual prognosis in eyes with PCV-related breakthrough VH is
      variable after vitrectomy. Initial polyps at the extrafoveal area led to better
      functional outcomes. Early vitrectomy may be beneficial for visual recovery after
      PCV-related VH.

PMID- 24924447
TI  - Colorectal cancer surgery remains effective with rising patient age.
AB  - BACKGROUND: The incidence of colorectal cancer rises disproportionally in aging
      persons. With a shift towards higher population age in general, an increasing
      number of older patients require adequate treatment. This study aims to
      investigate differences between young and elderly patients who undergo resection
      for colorectal cancer, regarding clinical characteristics, morbidity, and
      prognosis. METHODS: By retrospective analysis of 6 years (2007 to 2012) of a
      prospectively documented database, a total of 636 patients were identified who
      underwent oncological resection for colorectal cancer at our institution. Of this
      total, all 569 patients with primary colorectal adenocarcinoma were included.
      Four hundred ten patients were 74 years or younger and 159 were 75 years or
      older. The median follow-up was 22 months. RESULTS: Older patients had
      significantly more comorbidities (85 % vs. 56 %, p < 0.001) and a higher ASA
      score (p < 0.001). The mean length of stay in the hospital was longer (24 vs. 20
      days, p = 0.002), as was the length of postoperative intensive care stay (4 vs. 2
      days, p = 0.003). However, elderly patients did not have significantly higher
      rates of intraoperative complications or surgical morbidity. Tumor-specific 2
      year survival was 83 +/- 4 % for the elderly and 87 +/- 2 % for the younger
      patients, which was not significantly different (p = 0.90). CONCLUSIONS: Long
      term outcome after oncologic resection for colorectal cancer does not differ
      between elderly and younger patients. Age in general should not be considered as
      a limiting factor for colorectal cancer surgery or tumor-specific prognosis.

PMID- 24924448
TI  - Laparoscopy rather than colonoscopy for the diagnosis and treatment of fulminant
      ischemic colitis.

PMID- 24924446
TI  - Childhood glaucoma surgery in the 21st century.
AB  - Most children with glaucoma will require surgery in their lifetime, often in
      their childhood years. The surgical management of childhood glaucoma is however
      challenging, largely because of its greater potential for failure and
      complications as compared with surgery in adults. The available surgical
      repertoire for childhood glaucoma has remained relatively unchanged for many
      years with most progress owing to modifications to existing surgery. Although the
      surgical approach to childhood glaucoma varies around the world, angle surgery
      remains the preferred initial surgery for primary congenital glaucoma and a major
      advance has been the concept of incising the whole of the angle (circumferential
      trabeculotomy). Simple modifications to the trabeculectomy technique have been
      shown to considerably minimise complications. Glaucoma drainage devices maintain
      a vital role for certain types of glaucoma including those refractory to other
      surgery. Cyclodestruction continues to have a role mainly for patients following
      failed drainage/filtering surgery. Although the prognosis for childhood glaucoma
      has improved significantly since the introduction of angle surgery, there is
      still considerable progress to be made to ensure a sighted lifetime for children
      with glaucoma all over the world. Collaborative approaches to researching and
      delivering this care are required, and this paper highlights the need for more
      high-quality prospective surgical trials in the management of the childhood
      glaucoma. 

PMID- 24924449
TI  - Investigation of brain hemodynamic changes induced by active and passive
      movements: a combined arterial spin labeling-BOLD fMRI study.
AB  - PURPOSE: To assess the applicability of arterial spin labeling (ASL) in
      comparison to blood-oxygenation-level-dependent (BOLD) contrast fMRI in detecting
      brain activations elicited by active and passive hand movements. MATERIALS AND
      METHODS: A block design for ASL and BOLD fMRI was applied in 8 healthy subjects
      using active and passive hand tasks. Data analyses were performed at individual
      and group level, comparing both the different movements and the performance of
      the two techniques. RESULTS: Group analyses showed involvement of the same areas
      during both tasks, as the contralateral sensorimotor cortex, supplementary motor
      area, cerebellum, inferior parietal lobes, thalamus. ASL detected smaller
      activation volumes than BOLD, but the areas had a high degree of colocalization.
      Few significant differences (P < 0.05) were found when the two tasks were
      compared for the number of activated voxels, coordinates of center of mass, and
      CBF estimates. Considering together all the areas, the mean %BOLD change was 0.79
      +/- 0.27 and 0.73 +/- 0.24 for the active and passive movements respectively,
      while the mean %CBF changes were 34.1 +/- 8.9 and 27.1 +/- 14.8. CONCLUSION: Our
      findings confirm passive and active tasks are strongly coupled, supporting the
      importance of passive tasks as a diagnostic tool in the clinical setting. ASL
      fMRI proved suitable for functional mapping and quantifying CBF changes, making
      it a promising technique for patient cohort applications.

PMID- 24924450
TI  - [Consensus standpoints from expert panel of Chinese Society of Cardiology on
      AHA/ACC 2013 guideline on the treatment of blood cholesterol to reduce
      atherosclerotic cardiovascular risk in adults].

PMID- 24924451
TI  - [Echocardiography standardization training for cardiologist].

PMID- 24924452
TI  - [Chinese expert consensus on management of dyslipidemia in postmenopausal women].

PMID- 24924453
TI  - [Association between a new SNP in proximal promoter region of apolipoprotein M
      and susceptibility of coronary artery diseases in Han Chinese population].
AB  - OBJECTIVE: To investigate the association between genetic polymorphisms of
      proximal promoter region of apolipoprotein M (apoM) gene and susceptibility of
      coronary artery diseases (CAD) in Han Chinese population. METHODS: Two pairs of
      primers were designed according to the sequence (GenBank accession nos.
      EU030444.1) and the PCR products of apoM proximal promoter region were directly
      sequenced. Two hundred and six patients [165 males, mean age (61.9 +/- 9.2) years
      old] diagnosed with CAD according to the results of angiography (a lesion was
      classed as being significant when stenosis was more than 50%) were enrolled in
      the present study, 209 age- and gender-matched patients[157 males, mean age (60.4
      +/- 9.1) years old] without CAD according to the results of angiography were
      selected as the control group. The allelic frequencies and genotype distributions
      of polymorphism in CAD and non-CAD patients were analyzed. Furthermore the wide
      type and mutant promoter region of apoM were cloned into the luciferase
      expression vector pGL3, respectively. Luciferase reporter assay was used to
      detect the activity of apoM promoter. RESULTS: A new deletion mutation -724delC
      in apoM promoter was found. The frequency of Del C allele was 8.0% in CAD
      patients and only 4.1% in the non-CAD controls (OR = 2.054, 95%CI 1.125-3.749, P
      = 0.017). The mean TC level was lower in groups with wide-type homozygotes
      compared to the mutant allele carriers [ (6.04 +/- 0.90) mmol/L vs. (4.95 +/-
      1.00)mmol/L, P < 0.01]. -724delC mutant showed obvious decreased luciferase
      activities (1.13 +/- 0.25 vs. 2.11 +/- 0.15, P = 0.009). CONCLUSION: It is
      reasonable to speculate that -724delC could affect the activity of the apoM
      promoter and downregulate apoM expressions, therefore, influence the
      susceptibility of CAD in this patient cohort.

PMID- 24924454
TI  - [Low-density lipoprotein cholesterol target goal attainment rate and related
      factors in patients with acute coronary syndrome after percutaneous coronary
      intervention].
AB  - OBJECTIVE: To observe the low-density lipoprotein cholesterol (LDL-C) target goal
      attainment rate and related factors in patients with acute coronary syndrome
      (ACS) after percutaneous coronary intervention (PCI). METHODS: From March 2011 to
      March 2012, a total of 832 ACS patients were retrospectively evaluated in the
      Cardiology Department of the First Affiliated Hospital of Dalian Medical
      University. The target goal attainment rate after PCI was defined as the
      percentage of patients reaching LDL-C goals recommended by The European Society
      of Cardiology (ESC) and the European Atherosclerosis Society (EAS) guidelines for
      the management of dyslipidemias (European guidelines) and Chinese guidelines on
      prevention and treatment of dyslipidemias in adults and Chinese guidelines on
      percutaneous coronary artery intervention treatment (Chinese guidelines).
      Multivariate logistic regression analysis was used to analyze the related
      factors. RESULTS: According to the European guidelines, the overall LDL-C goal
      attainment rates at 1 month and 9 months after PCI were 25.2% (210/832) and 22.2%
      (186/832), respectively. According to the Chinese guidelines, the overall LDL-C
      goal attainment rates at 1 month and 9 months after PCI were 46.5% (387/832) and
      42.3% (352/832), respectively. In accordance with the Chinese guidelines, the
      multivariate logistic regression analysis showed that gender (females/males, OR =
      0.650, 95%CI: 0.442-0.956), age ( >= 60 years/<60 years, OR = 0.628, 95%CI:0.464
      0.850), hypertension (OR = 0.737, 95%CI: 0.547-0.994), prior myocardial
      infarction history (OR = 0.696, 95%CI:0.511-0.948), prior PCI history (OR =
      0.575, 95%CI: 0.339-0.974) and baseline LDL-C levels ( OR = 0.155, 95%CI: 0.096
      0.252) were independent risk factors that affected LDL-C goal attainment at 1
      month post PCI. Moreover, the following parameters were the independent risk
      factors for LDL-C goal attainment at 9 months after PCI: prior myocardial
      infarction history (OR = 0.706, 95%CI:0.521-0.958), prior PCI history (OR =
      0.565, 95%CI:0.334-0.957) and baseline LDL-C levels (OR = 0.176, 95%CI:0.110
      0.282). CONCLUSIONS: Currently, the LDL-C control rate is low in patients with
      ACS after PCI. The cholesterol lowering therapy should be individually
      strengthened for patients after PCI, especially in female patients, patients with
      aged >= 60 years old, hypertension, prior myocardial infarction history, prior
      PCI history and higher baseline LDL-C level.

PMID- 24924455
TI  - [Association of serum high-density lipoprotein cholesterol level and risk of
      recurrent ischemic stroke].
AB  - OBJECTIVE: To observe the association between high-density lipoprotein
      cholesterol (HDL-C) level and rate of ischemic stroke recurrence. METHODS: A
      total of 1 059 patients with ischemic stroke were enrolled from 5 community
      health centers and underwent baseline surveys during the period of January 2003
      to December 2006. After baseline surveys, patients were followed up every 6
      months until December 31, 2008. The new stroke events were recorded as the
      primary study endpoint. The association between HDL-C, HDL-C/TC and ischemic
      stroke recurrence was analyzed by Cox regression analysis. RESULTS: The
      proportions of stroke patients with high ( >= 1.55 mmol/L), moderate (1.04-1.54
      mmol/L) and low (<1.04 mmol/L) HDL-C levels were 15.58% (165/1 059) , 54.58%
      (578/1 059) and 29.84% (316/1 059) respectively. During a mean of (3.21 +/- 1.04)
      years follow-up, recurrent ischemic stroke was recorded in 137 patients. Compared
      with HDL-C >= 1.40 mmol/L group, multivariate Cox regression analysis showed that
      stroke recurrence rates of patients with HDL-C <= 1.00 mmol/L and ranged from
      1.01 to 1.19 mmol/L increased by 0.944 (HR = 1.944, 95%CI:1.033-3.659, P = 0.039)
      and 1.027 (HR = 2.027, 95%CI:1.116-3.682, P = 0.020)fold , respectively.
      Recurrence rates increased 1.237 (HR = 2.237, 95%CI:1.208-4.144, P = 0.010) fold
      in patients with HDL-C/TC <= 0.19 mmol/L compared to patients with HDL-C/TC >=
      0.28 mmol/L. CONCLUSION: The risk of ischemic stroke recurrence increases with
      decreasing HDL-C level or HDL-C/TC ratio.

PMID- 24924456
TI  - [Predict value of monitoring changes of urinary neutrophil gelatinase-associated
      lipocalin and kidney injury molecule-1 after coronary angiography and
      percutaneous coronary intervention on early diagnosis of contrast-induced
      nephropathy].
AB  - OBJECTIVE: To explore the predict value of monitoring changes of urinary
      neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule
      1(KIM-1) after coronary angiography (CAG) and percutaneous coronary intervention
      (PCI) on the early diagnosis of contrast-induced nephropathy(CIN). METHODS: One
      hundred and sixty patients underwent CAG and PCI were enrolled in this
      prospective study. There were 14 patients with CIN and non-CIN patients were
      selected with the proportion of 2: 1 (n = 28).Serum creatinine (SCr) was measured
      before and at 24, 48 and 72 h after the procedure. Urinary NGAL and KIM-1 were
      measured before and at 4 and 24 h after the procedure. The relationship between
      NGAL, KIM-1 and CIN were analyzed. Receiver operating characteristic (ROC) curve
      and area under the ROC curve (AUC) were used to analyze the diagnostic
      sensitivity and specificity of CIN by urinary NGAL and KIM-1. RESULTS: (1) The
      values of urinary NGAL was significantly higher in the CIN group than in non-CIN
      group at 4 h after CAG or PCI (P < 0.01); the value of urinary NGAL was
      significantly increased from the baseline to 4 h after the procedure in the CIN
      group (P < 0.01). (2) Uurinary KIM-1 levels of CIN group was significantly higher
      than in non-CIN group at 24 h after the CAG or PCI (P < 0.01) ; the urinary KIM-1
      levels was significantly increased from baseline to 24 h after the procedure in
      the CIN group (P < 0.01). (3) Pearson correlation analysis showed that there was
      a positive correlation between urinary NGAL and SCr (r = 0.814, P < 0.01) and
      urinary KIM-1(r = 0.758, P < 0.01) in the CIN group. (4) ROC curve analysis
      showed that the AUC for urinary NGAL was 0.897. When the cut-off value of NGAL
      was set at 11.950 ug/L, the sensitivity and specificity for the diagnosis of CIN
      were 92.9% and 71.4%, respectively. The AUC for urinary KIM-1 was 0.839. With the
      cut-off value of urinary KIM-1 set as 4.595 ug/L, the diagnostic sensitivity and
      specificity for CIN were 85.7% and 71.4%, respectively. CONCLUSIONS: Urinary NGAL
      serves as a good biomarker for early diagnosis of CIN suggesting acute kidney
      injury at 4 h post CAG and PCI. Urinary KIM-1 can reflect the change of renal
      function after contrast injection earlier than SCr and may also be a good
      biomarker for early diagnosis of CIN.

PMID- 24924457
TI  - [Value of evaluating diastolic function with the single-beat E/(e'*s) obtained by
      dual doppler echocardiograph in coronary heart disease patients with preserved
      left ventricular systolic function].
AB  - OBJECTIVE: To assess the value of E/(e'*s) in estimating left ventricular
      diastolic dysfunction in patients with coronary heart disease by dual Doppler
      echocardiograph. METHODS: Seventy-seven consecutive coronary heart disease
      patients with preserved systolic function underwent echocardiographic study were
      included. The E, e'and s were obtained by the dual Doppler echocardiography and
      E/(e'*s), E/e' were calculated. All patients underwent left ventricular
      catheterization to measure left ventricular end diastolic pressure (LVEDP). The
      relationship between E/(e'*s), E/e' and LVEDP were analyzed. Patients were
      divided into normal diastolic function (LVEDP < 12 mmHg, 1 mmHg = 0.133 kPa) and
      diastolic dysfunction group (LVEDP >= 12 mmHg) . RESULTS: (1) Pearson correlation
      analysis showed that both E/(e'*s) and E/e' correlated well with LVEDP (r = 0.68
      and r = 0.79, both P < 0.01). (2)Using receiver operating characteristic
      analysis, the optimal cut-off for E/(e'*s) was 1.2(sensitivity was 80%,
      specificity was 77%,AUC was 0.85) and for E/e' was 9.2(sensitivity was 74%,
      specificity was 81%,AUC was 0.87) to predict left ventricular diastolic
      dysfunction. When combined cut-offs of E/(e'*s) >= 1.2 and E/e' >= 9.2, the
      sensitivity and specificity of predicting left ventricular diastolic dysfunction
      were 83% and 71% respectively, and AUC was 0.87. CONCLUSIONS: E/(e'*s) can
      correctly reflect diastolic function status in patients with coronary artery
      disease. However, combined use of E/(e'*s)and E/e' does not add the prediction
      value on diastolic dysfunction in this patient cohort.

PMID- 24924458
TI  - [A multi-center survey on the therapeutic status of patients with acute
      myocardial infarction in Wuxi city of China].
AB  - OBJECTIVE: To explore the characteristics and therapies of patients with acute
      myocardial infarction (AMI) in Wuxi city, China. METHODS: A network was
      established to obtain information of patients with AMI who were admitted to 9
      designated hospitals between 2011 and 2012. A total of 1 714 patients were
      enrolled (1 334 males, 754 smokers, 1 076 hypertension, 270 hyperlipidemia and
      398 diabetes) including 1 410 patients with acute ST-segment elevation myocardial
      infarction (STEMI) and 304 patients with acute non ST-segment elevation
      myocardial infarction (NSTEMI). Patients' characteristics, therapies, the
      incidence of major adverse cardiovascular events (MACEs) and all-cause mortality
      were analyzed. RESULTS: (1) Medication therapy was as follows: antiplatelet
      therapy 98.3% (1 685 cases) , beta-blockers 59.1% (1 013 cases) , ACEI or ARB
      67.6% (1 159 cases) , statins 98.1% (1 682 cases) , and nitrates 71.1% (1 218
      cases) . Of the patients, 7.1% (132 cases) received temporary pacemakers, 34.0%
      (480 cases) with acute STEMI underwent reperfusion [direct PCI 18.4% (260 cases)
      and thrombolysis 15.6% (220 cases)]. (2) According to the hospital admission
      data, patients were divided into three groups: group A, transported to the
      hospital by ambulance (n = 361); group B, transported to the hospital by private
      vehicles (n = 1 318); and group C, AMI occurred in the hospital (n = 35). The
      median time of AMI onset to physician contact of the 3 groups was 178 min, 368
      min, and 9 min, respectively. The median time from AMI onset to the first ECG was
      181 min, 379 min, and 10 min, respectively. The median time from AMI onset to
      cardiology specialist consultation was 187 min, 431 min, and 69 min,
      respectively. AMI onset-to-physician contact, AMI onset-to-first ECG, and AMI
      onset-to-specialized treatment time was the shortest in group C, followed by
      group A and group B. For patients with STEMI underwent reperfusion therapy, the
      median AMI onset-to-reperfusion therapy time was significantly shorter in group A
      patients than group B patients [thrombolysis group: 224(171, 514) min vs. 378
      (158, 785) min, PCI group: 318 (154, 674) min vs. 489 (143, 816) min, all P <
      0.05]. (3) The total incidence of MACEs was 16.3% (279/1 714), the all-cause in
      hospital mortality rate was 13.1% (224/1 714). According to the AMI onset-to
      physician contact, patients were divided into 4 groups: <3 h, 3-6 h, 6-12 h, and
      >12 h. The incidence of MACEs [4.4% (23/517), 13.3% (60/451), 19.1% (77/404) and
      34.8% (119/342),chi(2) = 114.36, P < 0.01] and all-cause in-hospital mortality
      rate [4.1% (21/517) , 10.4% (47/451), 18.6% (75/404), 23.7% (81/342), chi(2) =
      84.36, P < 0.01] increased in proportion to the time of AMI onset-to-physician
      contact. Among STEMI patients, the incidence of MACEs [5.8% (15/260) , 12.3%
      (27/220) , 20.9% (194/930) ,chi(2) = 39.93, P < 0.01] and all-cause in-hospital
      mortality [1.5% (4/260) , 10.0% (22/220) , 18.2% (170/930) ,chi(2) = 50.90, P <
      0.01] was the lowest in the primary PCI group, followed by thrombolysis group and
      was the highest in the early conservative treatment group. CONCLUSIONS: Guideline
      is well followed in terms of drug treatments of AMI in this cohort, but only a
      small proportion of AMI patients in Wuxi received reperfusion therapy. There is a
      considerable out-of-hospital time delay for AMI patients in this cohort which is
      shorter in group A than in group B. All-cause in-hospital mortality and MACEs is
      the lowest in AMI patients underwent primary PCI.

PMID- 24924459
TI  - [Prevalence of symptomatic orthostatic hypotension and orthostatic blood pressure
      changes].
AB  - OBJECTIVE: To analyze the prevalence and orthostatic blood pressure changes in
      subjects with symptomatic orthostatic hypotension (OH), and to observe the
      relation between symptoms and orthostatic blood pressure change in this
      population. METHODS: A total of 193 subjects who consulted physicians due to OH
      related symptoms were selected, and divided into three groups: young (n = 37),
      middle-aged (n = 66) and elder (n = 90). Height, body weight, waist
      circumference, hip circumference and resting heart rate were measured. Symptom
      scores of every subject were obtained. CAVI and ABI were measured. Blood pressure
      including recumbent position, orthostatic systolic and diastolic blood pressure
      was measured at the morning and at the afternoon on two separate examination days
      with at least one week interval. After that, orthostatic changes in systolic
      blood pressure (OCs) and orthostatic changes in diastolic blood pressure (OCd)
      were calculated. RESULTS: OH prevalence was 32.6% in this cohort. The prevalence
      of three groups was similar [young: 32.4%, middle-aged: 25.8%, and elderly:
      37.8%, respectively (P > 0.05)]. Only 9 cases (14.29% of confirmed OH cases)
      reached the OH diagnostic criteria with equal or more than 2 times orthostatic
      blood pressure measurements. OH was diagnosed in 63 patients during the 4 times
      orthostatic blood pressure check, of which 19.5% to 57.14% cases were diagnosed
      with single orthostatic blood pressure check. Age, weight, body mass index, waist
      to-hip ratio, smoking, drinking habit, sex, coronary heart disease, hypertension,
      Parkinson's disease, stroke history, antihypertensive drug use were similar
      between OH group and non-OH group. Height, waist circumference, hip
      circumference, and resting heart rate were significantly lower in OH group than
      in non-OH group (P < 0.05). The values of the factors in OH group were lower.
      CAVI was 8.45 +/- 0.19 in non-OH group and 8.37 +/- 0.27 in OH group (P > 0.05),
      ABI was significantly lower in OH group than in non-OH group (1.004 +/- 0.013 vs.
      1.051 +/- 0.009, P < 0.01). CONCLUSION: The prevalence of OH in people with
      related symptoms is high. Repeated orthostatic blood pressure measurements can
      improve OH detection rate.

PMID- 24924460
TI  - [Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac
      remodeling and cardiac dysfunction following myocardial infarction in mice].
AB  - OBJECTIVE: To observe the impact of PDE5shRNA on cardiac remodeling and heart
      function following myocardial infarction in mice. METHODS: Myocardial infarction
      (MI) was induced in mice by left coronary artery ligation. Mice were randomly
      assigned to sham group (n = 6), PDE5shRNA group (n = 12), common adenovirus group
      (n = 15) and DMEM group (n = 8). Four weeks post-MI, the survival rate was
      evaluated. Cardiac function was examined by echocardiography. HE staining and
      Masson staining were used to evaluate the myocardial infarction size and
      fibrosis. The number of blood vessels was evaluated by immunohistochemistry, PDE5
      protein expression in the left ventricular was detected using Western blot, level
      of cGMP or PKG activity in the left ventricle was evaluated with ELISA. RESULTS:
      Four weeks post-MI, all mice survived in the sham group, 3(37%) mice died in the
      DMEM group, 1 (8%) died in the PDE5shRNA group and 5 died in the common
      adenovirus group (33%). Infarct size was significantly reduced in PDE5shRNA group
      compared with the common adenovirus group and DMEM group [(25.4 +/- 2.9)% vs.
      (42.0 +/- 3.2)% and (43.4 +/- 2.6) %, P < 0.05]. Cardiac function was
      significantly improved in PDE5shRNA group compared to common adenovirus group and
      DMEM group[LVFS: (21.1 +/- 3.7)% vs. (14.2 +/- 2.9)% and (14.22 +/- 2.91)%, all P
      < 0.05; LVEF: (48.2 +/- 7.1)% vs. (34.6 +/- 6.2)% and (38.1 +/- 2.8)%, all P <
      0.05; LVESD: (3.87 +/- 0.45) mm vs.(4.91 +/- 0.62) mm and (4.63 +/- 0.37) mm, all
      P < 0.05]. The blood vessel density was also higher in PDE5shRNA group compared
      with common adenovirus group (infarct area:14.3 +/- 2.0 vs. 6.6 +/- 1.2, P <
      0.05; periinfarct area: 23.6 +/- 2.1 vs. 13.7 +/- 2.4, P < 0.05). Compared with
      common adenovirus group, level of PDE5 was significantly downregulated and level
      of cGMP or PKG was significantly upregulated in PDE5shRNA group (all P < 0.05).
      CONCLUSIONS: Present study suggests PDE5shRNA improves cardiac function and
      attenuates cardiac remodeling through reducing infarction size and cardiac
      fibrosis and these beneficial effects are possibly mediated by activating
      cGMP/PKG signaling pathway.

PMID- 24924461
TI  - [Salidroside attenuates high glucose-induced apoptosis in human umbilical vein
      endothelial cells via activating the Ca(2)+/CaM/CAMKIIdelta/eNOS pathway].
AB  - OBJECTIVE: Endothelial oxidative stress plays an important role in the
      pathogenesis of cardiovascular disease. Salidroside, a phenylpropanoid glycoside
      isolated from Rhodiola rosea L, could exert potent antioxidant properties. In
      this study, we investigated the protective effects, and related mechanism of
      salidroside against high glucose (33 mmol/L)-induced cell damage in human
      umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were cultured in
      normal glucose (5.5 mmol/L), high glucose (33 mmol/L), high salidroside (10
      ug/ml+33 mmol/L glucose), moderate salidroside (4 ug/ml+33 mmol/L glucose), low
      salidroside (1 ug/ml+33 mmol/L glucose) and very low salidroside (0.1 ug/ml+33
      mmol/L glucose) for 48 h. Cell viability, the level of malondialdehyde (MDA) ,
      reactive oxygen species (ROS) , nitric oxide (NO) , [Ca(2)+]i, calmodulin (CaM) ,
      calmodulin-dependent kinase (CaMK) IIdelta, endothelial nitric oxide synthase
      (eNOS) , active caspase-3 protein expression and eNOS ser 1177 phosphorylation of
      HUVECs post various treatments were measured. The cell viability was assessed
      with MTT assay, and the level of ROS, and [Ca(2)+]i was analyzed using flow
      cytometry. Nitric oxide and MDA was detected by Nitric Oxide Assay Kit and MDA
      Assay Kit. Western blot was performed to detect the protein expressions of eNOS,
      active caspase-3 and eNOS ser 1177 phosphorylation. RESULTS: Comparing to the
      normal glucose group, high glucose treatment increased the cell damage, the level
      of NO and [Ca(2)+]i (P < 0.05) , downregulated CAMKIIdelta, eNOS expression and
      eNOS ser 1177 phosphorylation (P < 0.05), elevated the concentration of MDA and
      ROS (P < 0.05) in HUVECs. Salidroside treatment significantly attenuated high
      glucose-induce cell damage on cultured HUVECs in a dose-dependent manner.
      Comparing to the high glucose group, 10 ug/ml Salidroside significantly increased
      cell viability (P < 0.05) , inhibited high glucose-induced release of MDA ,
      generation of ROS, active caspase 3 protein expression (P < 0.05) , upregulated
      the release of nitric oxide and [Ca(2)+]i by HUVECs (P < 0.05) , enhanced CaM,
      CAMKIIdelta, eNOS expression and eNOS ser 1177 phosphorylation in HUVECs (P <
      0.05) . CONCLUSIONS: These findings suggeste that salidroside could attenuate
      high glucose induced apoptosis in HUVEC, partly through activating the
      Ca(2)+/CaM/CAMKIIdelta/eNOS pathway.

PMID- 24924462
TI  - [Meta-analysis of safety and efficacy on exercise rehabilitation in coronary
      heart disease patients post revascularization procedure].
AB  - OBJECTIVE: To evaluate the safety and efficacy of exercise rehabilitation in
      coronary heart disease patients post reascularization procedure. METHOD: We
      searched the Cochrane Central Register of Controlled Trials (CCRCT), Pubmed,
      Wanfang, CNKI, CBM and VIP database for randomized controlled trials (RCTs) on
      exercise rehabilitation for patients with coronary artery disease post
      percutaneous coronary intervention revascularization or coronary artery bypass
      grafting. Quality assessment and data collection were conducted by two reviewers
      independently. The data were analyzed by Review Manager 5.0. RESULTS: A total of
      3 474 patients from 16 RCTs were included in this meta-analysis and patients were
      divided into exercise rehabilitation group (n = 1 425) and control group (n = 2
      049). Meta-analysis results showed mortality rate was similar between the two
      groups (OR = 0.81, 95%CI 0.38-1.69, P > 0.05) and the incidence of major
      cardiovascular events rate (OR = 0.40, 95%CI 0.24-0.65, P < 0.01) and heart rate
      [mean difference (MD) = -2.82, 95%CI -4.72--0.92, P < 0.01] were significantly
      lower while LVEF (MD = 2.24, 95%CI 0.18-4.31, P < 0.05), the exercise metabolic
      equivalent (MD = 0.94, 95%CI 0.43-1.44, P < 0.01) , anaerobic threshold (MD =
      1.83, 95%CI 0.67-3.00, P < 0.01) , and maximum oxygen consumption (MD = 3.22,
      95%CI 2.42-4.03, P < 0.01) were significantly higher in exercise rehabilitation
      group than in control group. CONCLUSION: Exercise rehabilitation does not
      increase the risk of mortality in patients of coronary heart disease after
      revascularization and can effectively reduce major cardiovascular events.

PMID- 24924463
TI  - [A case of Cryoballoon ablation for persistent atrial fibrillation].

PMID- 24924464
TI  - [Primary right coronary angioplasty and stent implantation in an acute anterior
      myocardial infarction patient with dextrocardia and situs inversus].

PMID- 24924465
TI  - [Noninvasive imaging evaluation of aortico-left ventricular tunnel: a case
      report].

PMID- 24924466
TI  - [Prospective and value of cardiopulmonary exercise testing in clinical
      cardiovascular medicine].

PMID- 24924467
TI  - [Research update on the association between telocytes distribution with blood
      vessels on various tissues and the biological properties of telocytes].

PMID- 24924468
TI  - [Current epidemic status and intervention effect of common cardiovascular
      diseases in China].

PMID- 24924469
TI  - Evaluation of BSP expression and apoptosis in the periodontal ligament during
      orthodontic relapse: a preliminary study.
AB  - OBJECTIVE: To examine the expression of bone sialoprotein (BSP) and apoptosis in
      an in vivo orthodontic relapse model. MATERIALS AND METHODS: Male mice (10-12
      weeks old), either transgenic [green fluorescent protein (GFP) driven by the BSP
      promoter] or wild type, were used in this study. To achieve orthodontic tooth
      movement (OTM), maxillary right first molars were moved mesially using closed
      coil springs. Animals were divided into an OTM group (14 days continuous
      orthodontic force - 11 animals) or Relapse group (10 days of force application
      followed by 4 days of relapse - 8 animals). The control group was comprised of
      the contralateral maxillary molars. The periodontal ligament (PDL) was analyzed
      in areas of compression and tension for transgenic expression, osteoclast
      localization, and the presence of apoptotic cells. RESULTS: There was a
      significant decrease in GFP-labeled cells on the compression and tension sides of
      the PDL in the OTM group compared with control. In the relapse group, GFP-labeled
      cells were significantly decreased only on the old compression side. Osteoclasts
      were localized on the compression side of the OTM group, whereas in the Relapse
      group, they were present on both sides. PDL apoptosis significantly increased on
      the compression side in OTM and Relapse groups. CONCLUSION: Both OTM and Relapse
      groups exhibited a decreased number of GFP-labeled cells in areas of compression
      and tension. There was significant PDL apoptosis in regions under compressive
      forces following OTM and to a lesser extent following relapse.

PMID- 24924470
TI  - Preliminary experience with laparoscopic repair of associated inguinal and
      umbilical hernias in children.
AB  - PURPOSE: The authors report their preliminary experience in laparoscopic repair
      of associated inguinal and umbilical hernias in children. METHODS: Twenty-six
      patients affected by the association of inguinal and umbilical hernia with an
      umbilical defect larger than 5 mm underwent a laparoscopic procedure. A 5-mm
      trocar was placed through the umbilical defect for the optic. To fix the trocar
      to avoid loss of carboperitoneum, we fashioned and tightened a purse-string non
      absorbable suture with a sliding knot around the defect. In this manner, we
      ensured the trocar, fixing it and avoiding any loss of CO2, proceeding safely to
      the laparoscopic IH repair, by means of two additional 3 mm operative trocars. At
      the end of the inguinal herniorrhaphy, the previously fashioned purse-string
      suture was tightened to repair the umbilical defect. RESULTS: The mean operative
      time for the repair of associated inguinal and umbilical hernias was 30.1 +/- 7.4
      min in cases of unilateral inguinal hernia and 39.5 +/- 10.6 for bilateral
      inguinal hernia. Follow-up ranged from 8 to 32 months. Neither intra- nor post
      operative complications nor recurrences were seen. CONCLUSION: This small sample
      suggests that this simple method is safe, effective and might be useful for
      pediatric surgeons performing laparoscopic repair for inguinal hernia in presence
      of an associated UH with a statistically significant decrease of operative time.

PMID- 24924471
TI  - Bacteria in hernia sac: an important risk fact for surgical site infection after
      incarcerated hernia repair.
AB  - BACKGROUND: Although some recent reports have proven that incarcerated and/or
      strangulated hernia is not contraindication to mesh repair, there is still a
      common concern owing to increased rate of postoperative surgical site infection
      (SSI). The aim of this clinical study was to evaluate factors that increase the
      risk of SSI after incarcerated hernia repair, and to identify the pathogens
      related to SSI. METHODS: A retrospective analysis was performed on data collected
      prospectively over a 4-year interval from January 2007 to December 2011. A total
      of 121 patients who underwent emergency surgery for incarcerated hernias were
      analyzed. RESULTS: 107 hernias were repaired using mesh versus 14 primary suture
      repairs. SSIs were observed in 9 of the 121 patients. Of 15 preoperative and
      intraoperative variables studied, duration of symptoms, diabetes mellitus,
      present of ileus, bowel resection or mesh repair performed, bacteria present in
      hernia sac and cloudy fluid in hernia sac were found to be significant factors
      predicting SSI. On multivariate analysis only bowel resection, duration of
      symptoms and bacteria present in hernia sac were independent variables. The most
      common pathogen found in hernia sac and cultured from wound drainage or swab was
      Escherichia coli. The strains of bacteria cultured from wound drainage or swab
      were same as those cultured from fluid in hernia sac in six of nine patients.
      CONCLUSION: Gut-sourced E. coli is an important common organisms associated with
      SSI after incarcerated hernia repair. Prosthetic mesh could be used when no bowel
      resection is performed, duration of symptoms less than 24 h and fluid hernia sac
      is clear.

PMID- 24924472
TI  - Discourse Goals Affect the Process and Product of Nominal Metaphor Production.
AB  - Although a large number of studies have addressed metaphor comprehension, only a
      few attempts have so far been made at exploring the process of metaphor
      production. Therefore, in this paper, we address the problem of how people
      generate nominal metaphors or identify an apt vehicle for a given topic of
      nominal metaphors. Specifically, we examine how the process and product of
      metaphor production differ between two discourse goals of metaphor, namely an
      explanatory purpose (e.g., to clarify) and a literary purpose (e.g., to
      aesthetically pleasing). Experiment 1 analyzed the metaphors (or vehicles)
      generated in the metaphor production task, and demonstrated that people
      identified more prototypical exemplars of the property to be attributed to the
      topic as a vehicle for explanatory metaphors than for literary metaphors. In
      addition, it was found that metaphors generated for the explanatory purpose were
      more apt and conventional, and had high topic-vehicle similarity than those
      generated for the literary purpose, while metaphors generated for the literary
      purpose were more familiar and imageable than those for the explanatory purpose.
      Experiment 2 used a priming paradigm to assess the online availability of
      prototypical and less prototypical members of the topic property during metaphor
      production. The result was that both prototypical and less prototypical members
      were activated in producing literary metaphors, while neither members were
      activated in the production of explanatory metaphors. These findings indicate
      that the process of metaphor production is affected by discourse goals of
      metaphor; less prototypical members of the category are searched for a vehicle
      during the production of literary metaphors, and thus literary metaphors are
      generated with less prototypical vehicles than explanatory metaphors.

PMID- 24924473
TI  - Increased expression of phospho-acetyl-CoA carboxylase protein is an independent
      prognostic factor for human gastric cancer without lymph node metastasis.
AB  - Upregulation of acetyl-CoA carboxylase (ACC), as a rate-limiting enzyme of fatty
      acid synthesis,has been recognized in multiple human cancers, implicating a
      critical role in cancer development and progression; yet, its role in gastric
      cancer still remains unclear. In the present study, we detected ACC and
      phosphorylated form of ACC (pACC) expression in gastric cancers and explored its
      clinical significance. Tissue microarray blocks containing primary gastric cancer
      and adjacent normal mucosa specimens obtained from 1,072 Chinese patients were
      used for the detection of ACC and pACC expression by immunohistochemistry.
      Gastric cancer cell lines were treated by metformin, and pACC was measured by
      Western blotting. ACC overexpression was observed in all the tumor specimens.
      High expression of pACC was found in 630 (58.8 %) of the 1,072 primary tumors and
      in 237 (66.6 %) of the 356 primary tumors without lymph node metastasis.
      Absent/low expression of pACC significantly correlated with advanced T stage (P <
      0.001), tumor size (P = 0.010), lymph node metastasis (P < 0.001), advanced
      disease stage (P < 0.001), and poor histological differentiation (P = 0.014) in
      1,072 primary tumors, and with advanced T stage (P = 0.015), tumor size (P =
      0.017), and poor histological differentiation (P = 0.001) in 356 tumors without
      lymph node metastasis. Kaplan-Meier analysis showed that high expression of pACC
      is strongly related to better survival rates in all gastric cancer patients (P =
      0.006). Cox regression analysis revealed that pACC is an independent prognostic
      factor only in patients without lymph node metastasis (P = 0.016). Metformin
      treatment leaded to increased expression of pACC, which, in turn, resulted in the
      reduction of cell proliferation and colony formation of gastric cancer cells (P <
      0.05). Increased activation of ACC is frequent in human gastric cancer, and
      downregulation of pACC is an important prognostic factor, suggesting that
      ACC/pACC might be a potential target for cancer intervention.

PMID- 24924474
TI  - Increased CD59 protein expression is associated with the outcome of patients with
      diffuse large B-cell lymphoma treated with R-CHOP.
AB  - The objective was to investigate the expression and prognostic value of CD59
      expression in patients with diffuse large B-cell lymphoma (DLBCL) who underwent
      rituximab-cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). The
      immunohistochemical expressions of CD59 in 186 well-characterized DLBCL patients
      were evaluated using tissue microarrays and then were related to known tumor- and
      patient-related variables and to survival. The results show that CD59 expressions
      were not statistically different between the germinal center B-cell-like-type and
      the activated B-cell-like-type. We also analyzed the relationships of CD59
      expression with overall survival (OS) and progression-free survival (PFS) in
      DLBCL patients who were uniformly treated with R-CHOP. The high expression of
      CD59 was correlated with poor OS and PFS compared with the low-expression CD59.
      Our findings indicate that the CD59 level at onset is an independent predictor of
      the prognosis of DLBCL patients treated with R-CHOP. 

PMID- 24924475
TI  - Highly diastereodivergent synthesis of tetrasubstituted cyclohexanes catalyzed by
      modularly designed organocatalysts.
AB  - A highly diastereodivergent synthesis of tetrasubstituted cyclohexanes has been
      achieved using modularly designed organocatalysts (MDOs) which are self-assembled
      in situ from amino acids and cinchona alkaloid derivatives. Diastereodivergence
      is realized through controlling the stereoselectivity of the individual steps of
      a tandem Michael/Michael reaction. Up to 8 of the 16 possible stereoisomers have
      been successfully obtained in high stereoselectivities using MDOs for the tandem
      reaction and an ensuing epimerization. The method was used in the
      enantioselective synthesis of the natural products (-)-alpha- and beta-lycoranes.

PMID- 24924476
TI  - [Eight and a half plus syndrome as a first presentation of multiple sclerosis].

PMID- 24924477
TI  - The burden of imported malaria in Portugal 2003 to 2012.
AB  - Increasing international travel and expatriation to sub-Saharan countries where
      malaria is endemic has raised public health concerns about the burden of imported
      malaria cases in Portugal. From 2009 to 2012, there was a 60% increase in malaria
      hospitalizations, contradicting the declining trend observed since 2003. Older
      age was associated with longer length of stay in hospital and higher lethality. 

PMID- 24924478
TI  - Electron donation to an archaeal cytochrome P450 is enhanced by PCNA-mediated
      selective complex formation with foreign redox proteins.
AB  - Cytochrome P450 monooxygenases (P450s) are environmentally friendly biocatalysts
      that catalyze diverse chemical reactions using molecular oxygen under mild
      reaction conditions. P450s are activated upon receiving electrons from specific
      redox partner proteins, although the redox partners for most bacterial/archaeal
      P450s are not yet identified. Thus, it is important to establish a variety of
      efficient and versatile electron transfer systems from NAD(P)H to P450s for the
      design of biocatalysts. Sulfolobus solfataricus possesses a heterotrimeric
      proliferating cell nuclear antigen (PCNA). Fusion of the PCNA subunits to S.
      acidocaldarius P450 (CYP119) and the Pseudomonas putida redox proteins,
      putidaredoxin (PdX) and putidaredoxin reductase (PdR), yielded a selective
      protein complex containing one molecule each of the three proteins. The PCNA
      mediated heterotrimerization of CYP119, PdX, and PdR enhanced the CYP119
      activity, likely as a result of high local concentrations of the two redox
      proteins toward CYP119. Therefore, the PCNA-mediated formation of the complex
      containing PdX and PdR might be applicable for harnessing the utility of P450s
      whose redox partners are not yet identified. 

PMID- 24924480
TI  - Drawing circuits with carbon nanotubes: scratch-induced graphoepitaxial growth of
      carbon nanotubes on amorphous silicon oxide substrates.
AB  - Controlling the orientations of nanomaterials on arbitrary substrates is crucial
      for the development of practical applications based on such materials. The
      aligned epitaxial growth of single-walled carbon nanotubes (SWNTs) on specific
      crystallographic planes in single crystalline sapphire or quartz has been
      demonstrated; however, these substrates are unsuitable for large scale electronic
      device applications and tend to be quite expensive. Here, we report a scalable
      method based on graphoepitaxy for the aligned growth of SWNTs on conventional
      SiO2/Si substrates. The "scratches" generated by polishing were found to feature
      altered atomic organizations that are similar to the atomic alignments found in
      vicinal crystalline substrates. The linear and circular scratch lines could
      promote the oriented growth of SWNTs through the chemical interactions between
      the C atoms in SWNT and the Si adatoms in the scratches. The method presented has
      the potential to be used to prepare complex geometrical patterns of SWNTs by
      'drawing' circuits using SWNTs without the need for state-of-the-art equipment or
      complicated lithographic processes.

PMID- 24924479
TI  - Skin pigmentation, sun exposure and vitamin D levels in children of the Avon
      Longitudinal Study of Parents and Children.
AB  - BACKGROUND: It has been hypothesised that light skin pigmentation has arisen to
      ensure adequate levels of vitamin D as human populations moved out of Africa and
      into higher latitudes. Vitamin D, which is primarily obtained through exposure to
      sunlight (specifically ultraviolet radiation B (UVR-B)), has been inversely
      associated with several complex diseases. Greater sun exposure, on the other
      hand, is a well-known cause of skin cancer. The potential of UVR to be beneficial
      for some health outcomes but detrimental for others has prompted a public health
      debate on how to balance the positive and negative consequences of sun exposure.
      In this study we aimed to determine the validity of the evolutionary hypothesis
      linking lighter skin with higher vitamin D concentrations in a European
      population. Additionally, we aimed to examine the influence of pigmentation on
      personal behaviour towards sunlight exposure and the effects of this behaviour on
      vitamin D. METHODS: We combined genetic variants strongly associated with skin
      colour, tanning or freckling to create genetic scores for each of these
      phenotypes. We examined the association of the scores with pigmentary traits, sun
      exposure and serum 25-hydroxyvitamin D (25(OH)D) levels among children of the
      Avon Longitudinal Study of Parents and Children (ALSPAC, N = 661 to 5649).
      RESULTS: We found that fairer-skinned children, i.e. those with higher
      pigmentation score values, had higher levels of 25(OH)D (0.6 nmol/l; 95% CI 0.2,
      1.0; per unit increase in skin colour score; N = 5649). These children also used
      more protection against the damaging effects of UVR. CONCLUSIONS: In this
      population taking protective measures against sunburn and skin cancer does not
      seem to remove the positive effect that having a less pigmented skin has on
      vitamin D production. Our findings require further replication as skin
      pigmentation showed only a small effect on circulating 25(OH)D.

PMID- 24924481
TI  - Field evaluation of four widely used mosquito traps in Central Europe.
AB  - BACKGROUND: To monitor adult mosquitoes several trapping devices are available.
      These are differently constructed and use various mechanisms for mosquito
      attraction, thus resulting in different trapping sensitivities and efficacies for
      the various species. Mosquito monitoring and surveillance programs in Europe use
      various types of mosquito traps, but only a few comparisons have been conducted
      so far. This study compared the performance of four commercial trapping devices,
      which are commonly used in Europe. METHODS: Four different traps, Biogents
      Sentinel trap (BG trap), Heavy Duty Encephalitis Vector Survey trap (EVS trap),
      Centres for Disease Control miniature light trap (CDC trap) and Mosquito Magnet
      Patriot Mosquito trap (MM trap) were compared in a 4 * 4 latin square study. In
      the years 2012 and 2013, more than seventy 24-hour trap comparisons were
      conducted at ten different locations in northern and southern Germany,
      representing urban, forest and floodplain biotopes. RESULTS: Per 24-hour trapping
      period, the BG trap caught the widest range of mosquito species, the highest
      number of individuals of the genus Culex as well as the highest number of
      individuals of the species Ochlerotatus cantans, Aedes cinereus/geminus, Oc.
      communis and Culex pipiens/torrentium. The CDC trap revealed best performance for
      Aedes vexans, whereas the MM trap was most efficient for mosquitoes of the genus
      Anopheles and the species Oc. geniculatus. The EVS trap did not catch more
      individuals of any genus or species compared to the other three trapping devices.
      The BG trap caught the highest number of individuals per trapping period in urban
      environments as well as in wet forest, while the CDC trap caught the highest
      number of individuals in the floodplain biotopes. Additionally, the BG trap was
      most efficient for the number of mosquito species in urban locations. CONCLUSION:
      The BG trap showed a significantly better or similar performance compared to the
      CDC, EVS or MM trap with regard to trapping efficacy for most common mosquito
      species in Germany, including diversity of mosquito species and number of
      mosquitoes per trapping period. Thus, the BG trap is probably the best solution
      for general monitoring or surveillance programs of adult mosquitoes in Central
      Europe.

PMID- 24924482
TI  - Serum antibody to Porphyromonas gingivalis in metabolic syndrome among an older
      Japanese population.
AB  - BACKGROUND AND OBJECTIVE: Potentially significant associations between metabolic
      syndrome (MetS) and periodontal disease have been reported in recent studies;
      however, there is a dearth of literature regarding the relationship of MetS with
      serum antibody levels to periodontal pathogens. The aim of this cross-sectional
      study was to investigate the association between MetS and serum antibody to the
      periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in 216 Japanese
      individuals aged 79 years. MATERIALS AND METHODS: Serum antibody levels to P.
      gingivalis were measured by enzyme-linked immunosorbent assay. An elevated serum
      antibody response was defined as the upper quartile and was considered as the
      outcome variable. A multivariable logistic regression model was used to evaluate
      the association of MetS defined by the modified National Cholesterol Education
      Program Adult Treatment Panel III criteria with an elevated antibody status.
      Adjustments for gender, income, education, smoking status, dental-care
      utilisation patterns and brushing frequency were considered. RESULTS: The
      prevalence of MetS was 22.2% (n = 48). Study participants with MetS were 2.9
      times more likely to have an elevated serum antibody to P. gingivalis (adjusted
      odds ratio = 2.91, 95% confidence interval = 1.24-6.85) after simultaneous
      adjustment for other covariates. CONCLUSION: Our findings suggest an independent
      relationship between MetS and serum antibody levels to P. gingivalis in the
      Japanese elderly. Additional longitudinal epidemiologic studies with larger, more
      diversified samples and more complete information are needed to substantiate our
      findings.

PMID- 24924483
TI  - Autobiographical memory and psychological distress in a sample of upper-limb
      amputees.
AB  - Amputation is a traumatic and life-changing event that can take years to adjust
      to. The present study (a) examines psychological adjustment in a specific trauma
      exposed sample, (b) compares the phenomenology (e.g., vividness) of amputation
      related memories to more recent memories, and (c) tests whether memory
      phenomenology is associated with psychological distress. A total of 24 upper-limb
      amputees recalled two autobiographical memories--an amputation-related memory and
      a recent memory--and rated the phenomenological qualities of each memory,
      including Vividness, Coherence, Emotional Intensity, Visual Perspective, and
      Distancing. Participants also completed self-rated measures of psychological
      distress and personality. The sample was generally well adjusted; participants
      showed no relevant symptoms of anxiety and depression, and personality scores
      were similar to the general population. There were no significant differences in
      phenomenology between the two types of memories recalled. Even though amputation
      related memories were, on average, almost 20 years older than the recent
      memories, they retained their intense phenomenology. Despite the intensity of the
      memory, none of the phenomenological dimensions were associated with
      psychological distress. It is worth to further define which dimensions of
      phenomenology characterize memories of traumatic events, and their association
      with individuals' psychological reactions.

PMID- 24924484
TI  - Frontloading and intensity of skilled home health visits: a state of the science.
AB  - Frontloading of skilled nursing visits is one way home health providers have
      attempted to reduce hospital readmissions among skilled home health patients.
      Upon review of the frontloading evidence, visit intensity emerged as being
      closely related. This state of the science presents a critique and synthesis of
      the published empirical evidence related to frontloading and visit intensity.
      OVID/Medline, PubMed, and Scopus were searched. Seven studies were eligible for
      inclusion. Further research is required to define frontloading and visit
      intensity, identify patients most likely to benefit, and to provide a better
      understanding of how home health agencies can best implement these strategies. 

PMID- 24924485
TI  - Height, social comparison, and paranoia: an immersive virtual reality
      experimental study.
AB  - Mistrust of others may build upon perceptions of the self as vulnerable,
      consistent with an association of paranoia with perceived lower social rank.
      Height is a marker of social status and authority. Therefore we tested the effect
      of manipulating height, as a proxy for social rank, on paranoia. Height was
      manipulated within an immersive virtual reality simulation. Sixty females who
      reported paranoia experienced a virtual reality train ride twice: at their normal
      and reduced height. Paranoia and social comparison were assessed. Reducing a
      person's height resulted in more negative views of the self in comparison with
      other people and increased levels of paranoia. The increase in paranoia was fully
      mediated by changes in social comparison. The study provides the first
      demonstration that reducing height in a social situation increases the occurrence
      of paranoia. The findings indicate that negative social comparison is a cause of
      mistrust. 

PMID- 24924486
TI  - Aspirin and serum estrogens in postmenopausal women: a randomized controlled
      clinical trial.
AB  - Epidemiologic studies suggest a reduced risk of breast cancer among women who use
      aspirin. A plausible mechanism is through aspirin's effect on estrogens, possibly
      mediated through interference with estrogen synthesis via reduction in
      inflammation, which is increased in adipose tissues, including breast. In a
      randomized placebo-controlled trial, we evaluated the effects of six-month
      administration of 325 mg/day aspirin on serum estrogens (estradiol, estrone, free
      estradiol, and bioavailable estradiol) and sex hormone-binding globulin (SHBG) in
      144 healthy postmenopausal women. Eligible participants, recruited 2005-2007,
      were not taking nonsteroidal anti-inflammatory medication, including aspirin >2
      times/week or menopausal hormone therapy, and had a Breast Imaging-Reporting and
      Data System (BI-RADS) mammographic density classification of 2, 3, or 4. The
      intervention effects (intent-to-treat) were evaluated by differences in the
      geometric mean outcome changes at six months between aspirin and placebo groups
      using generalized estimating equations (GEE). Participants were a mean 59.4 (SD,
      5.4) years of age, with a mean body mass index (BMI) of 26.4 (SD, 5.4) kg/m(2).
      Between baseline and six months, none of the serum estrogens or SHBG changed
      substantially and there were no differences between groups. Stratifying by BMI
      did not change results. In conclusion, a single daily administration of 325 mg of
      aspirin for six months had no effect on serum estrogens or SHBG in postmenopausal
      women. Larger doses or longer duration of aspirin administration may be needed to
      affect circulating estrogens. Alternately, if aspirin influences breast cancer
      risk in postmenopausal women, it may do so through direct breast tissue effects,
      or through pathways other than estrogens.

PMID- 24924487
TI  - RNA-binding proteins regulate the expression of the immune activating ligand
      MICB.
AB  - The recognition of stress-induced ligands by the activating receptor NKG2D
      expressed on cytotoxic lymphocytes is crucial for the prevention and containment
      of various diseases and is also one of the best-studied examples of how danger is
      sensed by the immune system. Still, however, the mechanisms leading to the
      expression of the NKG2D ligands are far from being completely understood. Here,
      we use an unbiased and systematic RNA pull-down approach combined with mass
      spectrometry to identify six RNA-binding proteins (RBPs) that bind and regulate
      the expression of MICB, one of the major stress-induced ligands of NKG2D. We
      further demonstrate that at least two of the identified RBPs function during
      genotoxic stress. Our data provide insights into stress recognition and hopefully
      open new therapeutic venues. 

PMID- 24924488
TI  - Morphological and proteomic analysis reveal the role of pistil under pollination
      in Liriodendron chinense (Hemsl.) Sarg.
AB  - Pollination is an important physiological process during which interaction
      between pollen and pistil occurs. This interaction could determine whether or not
      fertilization will occur and hence the ratio of plant seed setting. Liriodendron
      chinense (Hemsl.) Sarg. (L. chinense) exhibits a distinct phenomenon where seed
      setting ratio is not more than 10% in natural environment. To explore the origin
      of this phenomenon, we conducted a comparative morphological and proteomic
      analysis on L. chinense pistils upon pollination. The morphological analysis
      showed that pollen grows well in vitro, but much slower on pistil or nutrient
      medium containing pistil extract. Proteomic analysis showed that 493 proteins had
      changed the expression after pollination. Among them, 468 and 51 proteins were
      identified by isobaric tags for relative and absolute quantitation and two
      dimensional gel electrophoresis respectively, and 26 proteins were common in the
      two methods. After proteins functional categorization, 66 differentially
      expressed proteins that are involved in reproduction process were found. Further
      analysis showed that among the reproductive process related proteins, protein
      disulfide-isomerase A6 and four embryo-defective proteins showed closer relations
      with the low seed setting phenomenon. The results indicated that the element from
      pistil might be the main reason leading to low seed setting in L. chinense, which
      will provide new insights in the mechanisms underlying L. chinense reproduction
      process. 

PMID- 24924489
TI  - Oral misoprostol for induction of labour.
AB  - BACKGROUND: Misoprostol is an orally active prostaglandin. In most countries
      misoprostol is not licensed for labour induction, but its use is common because
      it is cheap and heat stable. OBJECTIVES: To assess the use of oral misoprostol
      for labour induction in women with a viable fetus. SEARCH METHODS: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (17 January 2014).
      SELECTION CRITERIA: Randomised trials comparing oral misoprostol versus placebo
      or other methods, given to women with a viable fetus for labour induction. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trial data,
      using centrally-designed data sheets. MAIN RESULTS: Overall there were 76 trials
      (14,412) women) which were of mixed quality.In nine trials comparing oral
      misoprostol with placebo (1109 women), women using oral misoprostol were more
      likely to give birth vaginally within 24 hours (risk ratio (RR) 0.16, 95%
      confidence interval (CI) 0.05 to 0.49; one trial; 96 women), need less oxytocin
      (RR 0.42, 95% CI 0.37 to 0.49; seven trials; 933 women) and have a lower
      caesarean section rate (RR 0.72, 95% CI 0.54 to 0.95; eight trials; 1029
      women).In 12 trials comparing oral misoprostol with vaginal dinoprostone (3859
      women), women given oral misoprostol were less likely to need a caesarean section
      (RR 0.88, 95% CI 0.78 to 0.99; 11 trials; 3592 women). There was some evidence
      that they had slower inductions, but there were no other statistically
      significant differences.Nine trials (1282 women) compared oral misoprostol with
      intravenous oxytocin. The caesarean section rate was significantly lower in women
      who received oral misoprostol (RR 0.77, 95% CI 0.60 to 0.98; nine trials; 1282
      women), but they had increased rates of meconium-stained liquor (RR 1.65, 95% CI
      1.04 to 2.60; seven trials; 1172 women).Thirty-seven trials (6417 women) compared
      oral and vaginal misoprostol and found no statistically significant difference in
      the primary outcomes of serious neonatal morbidity/death or serious maternal
      morbidity or death. The results for vaginal birth not achieved in 24 hours,
      uterine hyperstimulation with fetal heart rate (FHR) changes, and caesarean
      section were highly heterogenous - for uterine hyperstimulation with FHR changes
      this was related to dosage with lower rates in those with lower doses of oral
      misoprostol. However, there were fewer babies born with a low Apgar score in the
      oral group (RR 0.60, 95% CI 0.44 to 0.82; 19 trials; 4009 babies) and a decrease
      in postpartum haemorrhage (RR 0.57, 95% CI 0.34 to 0.95; 10 trials; 1478 women).
      However, the oral misoprostol group had an increase in meconium-stained liquor
      (RR 1.22, 95% CI 1.03 to 1.44; 24 trials; 3634 women). AUTHORS' CONCLUSIONS: Oral
      misoprostol as an induction agent is effective at achieving vaginal birth. It is
      more effective than placebo, as effective as vaginal misoprostol and results in
      fewer caesarean sections than vaginal dinoprostone or oxytocin.Where misoprostol
      remains unlicensed for the induction of labour, many practitioners will prefer to
      use a licensed product like dinoprostone. If using oral misoprostol, the evidence
      suggests that the dose should be 20 to 25 mcg in solution. Given that safety is
      the primary concern, the evidence supports the use of oral regimens over vaginal
      regimens. This is especially important in situations where the risk of ascending
      infection is high and the lack of staff means that women cannot be intensely
      monitored.

PMID- 24924491
TI  - In Saccharomyces cerevisiae fructose-1,6-bisphosphate contributes to the Crabtree
      effect through closure of the mitochondrial unspecific channel.
AB  - In Saccharomyces cerevisiae addition of glucose inhibits oxygen consumption, i.e.
      S. cerevisiae is Crabtree-positive. During active glycolysis hexoses-phosphate
      accumulate, and probably interact with mitochondria. In an effort to understand
      the mechanism underlying the Crabtree effect, the effect of two glycolysis
      derived hexoses-phosphate was tested on the S. cerevisiae mitochondrial
      unspecific channel (ScMUC). Glucose-6-phosphate (G6P) promoted partial opening of
      ScMUC, which led to proton leakage and uncoupling which in turn resulted in,
      accelerated oxygen consumption. In contrast, fructose-1,6-bisphosphate (F1,6BP)
      closed ScMUC and thus inhibited the rate of oxygen consumption. When added
      together, F1,6BP reverted the mild G6P-induced effects. F1,6BP is proposed to be
      an important modulator of ScMUC, whose closure contributes to the "Crabtree
      effect". 

PMID- 24924492
TI  - Unusual photoluminescence properties of the 3D mixed-lanthanide-organic
      frameworks induced by dimeric structures: a theoretical and experimental
      approach.
AB  - The present work describes a complementary experimental and theoretical
      investigation of the spectroscopic properties of the four isostructural 3D Ln
      MOFs (wherein PDC = pyrazole-3,5-dicarboxylate, [La2(PDC)3(H2O)4].2H2O (1),
      [(La0.9Eu0.1)2(PDC)3(H2O)4].2H2O (2), [(La0.9Tb0.1)2(PDC)3(H2O)4].2H2O (3) and
      [(La0.9Eu0.5Tb0.5)2(PDC)3(H2O)4].2H2O (4)). The experimental data and theoretical
      calculations show that the singular photophysical properties presented by these
      Ln-MOFs are induced by strong interaction between the Ln(3+) ions.

PMID- 24924490
TI  - Assessment of the extirpated Maritimes walrus using morphological and ancient DNA
      analysis.
AB  - Species biogeography is a result of complex events and factors associated with
      climate change, ecological interactions, anthropogenic impacts, physical
      geography, and evolution. To understand the contemporary biogeography of a
      species, it is necessary to understand its history. Specimens from areas of
      localized extinction are important, as extirpation of species from these areas
      may represent the loss of unique adaptations and a distinctive evolutionary
      trajectory. The walrus (Odobenus rosmarus) has a discontinuous circumpolar
      distribution in the arctic and subarctic that once included the southeastern
      Canadian Maritimes region. However, exploitation of the Maritimes population
      during the 16th-18th centuries led to extirpation, and the species has not
      inhabited areas south of 55 degrees N for ~250 years. We examined genetic and
      morphological characteristics of specimens from the Maritimes, Atlantic (O. r.
      rosmarus) and Pacific (O. r. divergens) populations to test the hypothesis that
      the first group was distinctive. Analysis of Atlantic and Maritimes specimens
      indicated that most skull and mandibular measurements were significantly
      different between the Maritimes and Atlantic groups and discriminant analysis of
      principal components confirmed them as distinctive groups, with complete
      isolation of skull features. The Maritimes walrus appear to have been larger
      animals, with larger and more robust tusks, skulls and mandibles. The mtDNA
      control region haplotypes identified in Maritimes specimens were unique to the
      region and a greater average number of nucleotide differences were found between
      the regions (Atlantic and Maritimes) than within either group. Levels of
      diversity (h and pi) were lower in the Maritimes, consistent with other studies
      of species at range margins. Our data suggest that the Maritimes walrus was a
      morphologically and genetically distinctive group that was on a different
      evolutionary path from other walrus found in the north Atlantic. 

PMID- 24924493
TI  - Circadian differences in maze performance of C57BI/6 Ola mice.
AB  - The diurnal expression of performance in a six-point alley-T-maze was studied in
      C57BI/6 Ola mice. Besides the error rate, the latency time for leaving the start
      box as well as the number of alleys entered per min were determined. From 08.00
      hrs on, a group of 10 animals was investigated every four hours. Each group
      received one trial per day. Home cage activity was continously monitored over a
      14-day period. The results revealed the development of a circadian rhythm of maze
      performance in the course of training, which became significant as from the 4th
      day. The best maze performance was observed in the middle of the dark phase, from
      23.07 to 03.15 hrs. No indication of a direct relationship between home cage and
      ambulatory activity in the maze could be found. 

PMID- 24924494
TI  - Egg sac guarding by the funnel-web spider coelotes terrestris: function and
      development.
AB  - A number of spider species present a pattern of maternal behaviour labelled 'egg
      sac guardingrs which consist of remaining close to the egg sac throughout the
      incubation period. The present study aims at assessing the function of this
      behaviour and at casting some light on its control mechanisms in Coelotes
      terrestris, a species which, unlike those previously studied, is sedentary and
      presents extended care of the young. Field and laboratory experiments have shown
      that the mother had a determining role in the protection of her progency against
      predators,which may include certain conspecifics, and parasites (acaria and
      moulds). Confronting females at various stages of the reproductive cycle with non
      guarded egg sacs provided a certain amount of information on the development of
      egg guarding. Sub-adults ignored the egg sac (neither cannibalism nor egg
      guarding). Cannibalism was only exhibited by inseminated females which had not
      yet oviposited. The onset of egg guarding seemed to be linked with oviposition.
      No external stimulations were necessary for its maintenance and no extinction was
      observed. This indicated that the mother-young interactions which took place
      after emergence did not interfere with the tendency to guard the egg sac. 

PMID- 24924495
TI  - Effects of substrate brightness differences on isopod (Porcellio scaber) turning
      and turn alternation.
AB  - Woodlice ran faster in a straight runway when the floor was white than when it
      was black. When a runway with totally black or white floors (reflecting different
      levels of light) met up with equal areas of both brightnesses, woodlice turned in
      the direction of the runway brightness. Normal turn alternation after a forced
      turn was suppressed by this tendency to continue following the same substrate
      brightness when it involved moving in the direction of a repeating turn. However,
      when it involved turning in the direction of an alternating turn, the tendency to
      follow the same brightness had no effect on alternation. 

PMID- 24924496
TI  - Social processes and innovative behaviour in changing groups of lemur fulvus.
AB  - A group of brown lemurs was presented with one or two baited food-boxes requiring
      a specific type of motor response in order to be opened. Subsequently, four
      groups containing different combinations of experienced individuals from the
      original group and naive individuals were tested. Solutions to the problem and
      access to the food were recorded and considered in relation to social factors. In
      the original group, two adult males learned to open the boxes, with one male
      increasingly preventing the other from approaching. In the second group, with the
      subordinate male and certain females removed, the dominant male tolerated
      successful performances by a juvenile female. Group 3 consisted of three passive
      female participants from the original group and a naive female; one of the three
      original females now became the sole box-opener. The introduction of the
      subordinate male from the original group into the all-female group led to a
      sharing of box-opening by this subject and the skilled female. In the final
      group, intense aggression toward the skilled female by a new, naive adult male
      resulted in two previously passive females succeeding on some occasions. In
      lemurs, at least some 'scroungers' appear able to learn to perform a new act when
      the social context permits. 

PMID- 24924497
TI  - Failure to find positive key-press contrast for milk reinforcers using a within
      session procedure.
AB  - Rats pressed keys for sweetened condensed milk delivered by multiple schedules.
      Component duration varied from five seconds to 16 minutes. Positive contrast did
      not occur for any duration. That is, the rate of responding emitted during a
      variable interval component of a multiple schedule was not greater when the other
      component was extinction than when it was an identical variable interval
      schedule. The function that related key pressing to component duration also
      differed from that reported by past studies of pigeons pecking keys. Finding such
      functional differences suggests that behavioral contrast may be mediated by
      different mechanisms for different responses. It also implies that neither
      differences in the rates of responding, nor differences in the parts of the body
      utilized by the response, produced past functional differences in the observation
      of contrast for different responses. 

PMID- 24924498
TI  - Probability and delay of reinforcement: an examination of Mazur's equivalence
      rule.
AB  - It has recently been proposed that the probability of an event (e.g. delivery of
      a reinforcer) can be interpreted as functionally equivalent to the delay of an
      event. The present experiment examined the equivalence rule that states that
      reinforcer probability is functionally equivalent to a set of variable delays. A
      titration procedure was used in which pigeons chose between a standard,
      probabilistic alternative, and an adjusting, delayed alternative. Reinforcer
      probability was manipulated by varying the number of keypecks required to obtain
      a reinforcer. The duration of the adjusting alternative varied as a function of a
      pigeon's previous choices. There were six standard probabilities. The results
      indicated that the pigeons were sensitive to changes in the standard
      probabilities and that there were significant relations between: (1) reinforcer
      probability and the mean adjusted delay of reinforcement, and (2) the obtained
      and predicted adjusted delays. The present results support Mazur's conception of
      the relation between reinforcer probability and delay, and extend his conception
      to a different method of manipulating reinforcer probability. 

PMID- 24924499
TI  - Unexpected discrimination strategy used by pigeons.
AB  - Pigeons were conditioned with a symbolic matching-to-sample paradigm. Six visual
      patterns in 16 configurations were presented in an operant chamber where
      reinforcement was delivered next to the correct keys. A test with novel
      configurations, planned to demonstrate associative transitivity between
      equivalent stimuli, revealed instead a different but consistent behavior. An
      explanation for this behavior was sought in further tests and in a detailed post
      hoc analysis of the training configuration. The analysis revealed an overall
      location imbalance of the comparison stimuli in relation to the reinforcement
      sites. This apparently led to response side biases controlled by these lateral
      stimuli. The results of additional tests accorded with this hypothesis. The
      directing effect was unequivocal when both lateral stimuli biased a response in
      the same direction. When the directing effects by these stimuli were opposite,
      the animals only solved the task when they could resort to a rote learning of
      individual configurations. The characteristics of the rules that were identified
      are contrasted with those that have previously been thought to operate during
      conditional discrimination learning. 

PMID- 24924500
TI  - A tale of two mechanisms: a meta-analytic approach toward understanding the
      autonomic basis of cardiovascular reactivity to acute psychological stress.
AB  - A series of meta-analyses was undertaken to determine the contributions of
      sympathetic and parasympathetic activation to cardiovascular stress reactivity. A
      literature search yielded 186 studies of sufficient quality that measured indices
      of sympathetic (n = 113) and/or parasympathetic activity (n = 73). A range of
      psychological stressors perturbed blood pressure and heart rate. There were
      comparable aggregate effects for sympathetic activation, as indexed by increased
      plasma epinephrine and norepinephrine, and shortened pre-ejection period and
      parasympathetic deactivation, as indexed by heart rate variability measures.
      Effect sizes varied with stress task, sex, and age. In contrast to alpha
      adrenergic blockade, beta-blockade attenuated cardiovascular reactivity.
      Cardiovascular reactivity to acute psychological stress would appear to reflect
      both beta-adrenergic activation and vagal withdrawal to a largely equal extent.

PMID- 24924501
TI  - [Shoulder girdle, AC and SC joints].

PMID- 24924502
TI  - [Surgical stabilization of acute/chronic sternoclavicular instability with
      autologous gracilis tendon graft].
AB  - SURGICAL OBJECTIVE: Restoration of joint stability and unimpaired, painless
      shoulder function INDICATIONS: Chronic and recurrent painful instabilities of the
      sternoclavicular (SC) joint. Locked posterior instability. CONTRAINDICATIONS: A
      lack of autologous tendon grafts due to harvesting of all hamstring grafts during
      prior surgical procedures and general contraindications for surgery/anesthesia.
      SURGICAL TECHNIQUE: Joint stability is restored by a gracilis tendon allograft
      passed through two drill holes in the sternum and the medial clavicle using a
      figure-of-eight configuration. POSTOPERATIVE MANAGEMENT: Immobilization in a
      sling for 6 weeks with passive motion exercises followed by 6 weeks of active
      mobilization without weight-bearing. After 12 weeks, continuous remobilization
      with increasing weight-bearing. RESULTS: SC joint reconstruction using an
      autologous tendon graft in a figure-of-eight configuration can significantly
      improve shoulder function and pain relief. However, some impairment of shoulder
      function or persistent complaints may occur, which must be discussed with the
      patient in the preoperative setting.

PMID- 24924503
TI  - [Arthroscopically assisted reconstruction of acute and chronic AC joint
      separations].
AB  - OBJECTIVE: The surgical procedure aims at anatomic reduction and stabilization of
      the acromioclavicular joint in vertical and horizontal planes for acute
      separations using a trans-clavicular and trans-coracoidal suture tape fixation
      with additional acromioclavicular joint augmentation with a PDS cord cerclage.
      For chronic instability adding a tendon graft is essential for sustainable
      stability. INDICATIONS: Acute und chronic acromioclavicular joint separations
      type Rockwood III-VI. Recurrent AC-joint instability with intact coracoid process
      (with tendon graft). CONTRAINDICATIONS: Acromioclavicular joint separations type
      Rockwood I-II. Asymptomatic chronic AC-separations type Rockwood III-IV. Fracture
      close to base of coracoid process General contraindications for (elective)
      surgery. SURGICAL TECHNIQUE: Vertical reconstruction of the coraco-clavicular
      ligaments using a drill-guide for trans-clavicular and trans-coracoidal tunnel
      placement for high-strength suture tapes over titanium buttons. Additional
      stabilization of the AC-joint with a transosseus figure of 8 PDS suture cord
      cerclage. POSTOPERATIVE MANAGEMENT: Postoperatively the arm is put in a regular
      sling for 6 weeks. Free active range of motion of wrist and elbow. Shoulder range
      of motion is limited to 30 degrees  of flexion and abduction and 80 degrees 
      internal and 0 degrees  external rotation for 2 weeks. Extended to active
      assisted 45 degrees  flexion and abduction in weeks 3 and 4 and advanced to 60
      degrees  flexion/abduction and free internal/external rotation in weeks 5 and 6.
      Range of motion is unlimited from week 7. Full daily life activities after 3
      months, high-impact sports after 5-6 months postoperatively. RESULTS: The
      presented surgical technique reliably stabilizes the acromioclavicular joint.
      It's biomechanical properties with only the single-tunnel coracoclavicular suture
      tapes is on the level of the native vertical stability, which can be additionally
      improved for better horizontal stability with the cerclage over the AC-joint.

PMID- 24924504
TI  - [Open anatomic reconstruction of chronic acromioclavicular instability].
AB  - OBJECTIVE: The aim of open anatomic reconstruction of the acromioclavicular (AC)
      joint is combined reconstruction of the AC and coracoclavicular ligaments using a
      tendon graft. INDICATIONS: Symptomatic instabilities of the AC joint > type III.
      CONTRAINDICATIONS: Asymptomatic instabilities < type III and general
      contraindication against elective surgery. SURGICAL TECHNIQUE: Through the open
      surgical approach, the exact anatomical insertion sites of the ligamentous
      structures can be reproduced. In addition, this approach enables accurate
      repositioning of the AC joint under direct vision (including possible debridement
      of the intraarticular discus) and an additional fixation of deltotrapezoidal
      fascia. POSTOPERATIVE MANAGEMENT: Postoperatively, the arm is positioned in an
      abduction brace for 6-8 weeks. Passive exercises in flexion up to 90 degrees  and
      in external rotation up to 30 degrees  are permitted during this period. After 6
      8 weeks, free and active motion is allowed. RESULTS: Between January 2003 and
      December 2010, 46 patients (9 women and 37 men, mean age 42 +/- 13 years)
      underwent AC combined reconstruction. Complete outcome data were available for 25
      patients. Mean length of follow-up was 31 +/- 26 months. The mean preoperative
      coracoclavicular distance was 20.1 +/- 5.6 mm; postoperatively the mean distance
      was 7.1 +/- 3.0 mm (p < 0.001) The mean clinical scores also statistically
      improved (p < 0.001): American Shoulder and Elbow Score improved from 53.4 +/-
      18.7 points preoperatively to 80.6 +/- 25.7 points postoperatively and the
      Constant Murley Score improved from 60.0 +/- 16.7 points preoperatively to 85.2
      +/- 22.8 points postoperatively.

PMID- 24924505
TI  - [Arthroscopic resection of the acromioclavicular joint].
AB  - OBJECTIVE: Arthroscopic resection of the painful and degenerative altered
      acromioclavicular (AC) joint without destabilization of the joint and therefore
      pain relief and improvement in function. INDICATIONS: Conservative failed therapy
      of painful AC joint osteoarthritis. Impingement caused by caudal AC joint
      osteophytes. Lateral clavicular osteolysis. CONTRAINDICATIONS: General
      contraindications (infection, local tumor, coagulation disorders), higher grade
      instability of the AC joint (resection only together with stabilization).
      SURGICAL TECHNIQUE: Diagnostic glenohumeral arthroscopy. Treatment of
      accompanying lesions (subacromial impingement, rotator cuff, long head of
      biceps). Subacromial arthroscopy with bursectomy (partial) and visualization of
      the AC joint. Resection of caudal osteophytes. Localization of the anterior
      portal using a spinal needle in the outside-in technique. Resection of 2-3 mm of
      the acromial side and the 3-4 mm of the clavicular side with shaver/acromionizer.
      RESULTS: An isolated open AC joint resection was performed in 9 studies and an
      arthroscopic resection in 6 studies. Good and very good results were obtained in
      79% (range 54-100%) in open resection and 91% (range 85-100%) in arthroscopic
      resections. Patients were able to return to activities of daily life more quickly
      after arthroscopic resections than after open surgery.

PMID- 24924507
TI  - [Acromion reconstruction after arthroscopic subacromial decompression and
      iatrogenic acromial destruction].
AB  - OBJECTIVE: Reconstruction of the acromion, to achieve pain relief and better
      function of the deltoid muscle. INDICATIONS: After partial or complete removal of
      the acromion. CONTRAINDICATIONS: General surgical contraindications. Paresis of
      the axillary nerve. SURGICAL TECHNIQUE: Strategy of the operation with X-ray and
      CT scan. Patient in beach chair position. Disinfection of the shoulder and
      lateral pelvic region. Exploration of the defect area and searching for the
      lateral clavicula and spinascapulae end. Removal of a pelvic bone block. Fixation
      of the pelvic bone block to the spina scapulae with K-wires and finally
      osteosynthesis by a Reco plate (Synthes, Umkirch, Germany), wound closure.
      POSTOPERATIVE MANAGEMENT: For the first 6 weeks, a cast with the arm in 90
      degrees  abduction. Passive motion without the cast should be performed once a
      day. Starting in week 7, weekly reduction of abduction (90 degrees /60 degrees
      /30 degrees /0 degrees ). Active mobilization starting in week 10. Start to
      practice with weight bearing in week 13. RESULTS: Pain relief improved from VAS 7
      9 to VAS 2-3. Improved ROM can be seen postoperatively and after 6 months for
      abduction/adduction 50-0-50 degrees , anteversion/retroversion 80-0-10 degrees ,
      rotation out/in 40-0-10 degrees .

PMID- 24924506
TI  - [Distal clavicle fracture].
AB  - OBJECTIVE: Reposition and fixation of unstable distal clavicle fractures with a
      low profile locking plate (Acumed, Hempshire, UK) in conjunction with a
      button/suture augmentation cerclage (DogBone/FibreTape, Arthrex, Naples, FL,
      USA). INDICATIONS: Unstable fractures of the distal clavicle (Jager and Breitner
      IIA) in adults. Unstable fractures of the distal clavicle (Jager and Breitner IV)
      in children. Distal clavicle fractures (Jager and Breitner I, IIB or III) with
      marked dislocation, injury of nerves and vessels, or high functional demand.
      CONTRAINDICATIONS: Patients in poor general condition. Fractures of the distal
      clavicle (Jager and Breitner I, IIB or III) without marked dislocation or
      vertical instability. Local soft-tissue infection. SURGICAL TECHNIQUE:
      Combination procedure: Initially the lateral part of the clavicle is exposed by a
      4 cm skin incision. After reduction of the fracture, stabilization is performed
      with a low profile locking distal clavicle plate. Using a special guiding device,
      a transclavicular-transcoracoidal hole is drilled under arthroscopic view.
      Additional vertical stabilization is arthroscopically achieved by shuttling the
      DogBone/FibreTape cerclage from the lateral portal cranially through the
      clavicular plate. The two ends of the FibreTape cerclage are brought cranially
      via adjacent holes of the locking plate while the DogBone button is placed under
      the coracoid process. Thus, plate bridging is achieved. Finally reduction is
      performed and the cerclage is secured by surgical knotting. POSTOPERATIVE
      MANAGEMENT: Use of an arm sling for 6 weeks. RESULTS: Due to the fact that the
      described technique is a relatively new procedure, long-term results are lacking.
      In the short term, patients postoperatively report high subjective satisfaction
      without persistent pain.

PMID- 24924508
TI  - [Arthroscopic nerve release and decompression of ganglion cysts around the
      shoulder joint].
AB  - OBJECTIVE: Arthroscopic visualisation and release of nerves around the shoulder,
      decompression of ganglion cysts. INDICATIONS: Arthroscopic treatment of nerve
      entrapment syndromes around the shoulder (suprascapular nerve, axillary nerve).
      Arthroscopic visualisation and release of osseous or ligamentous structures
      causing nerve entrapment. Arthroscopic decompression and resection of periglenoid
      ganglion cysts. Arthroscopic release of concomitant lesions (labrum, rotator
      cuff, biceps). CONTRAINDICATIONS: No clinical or neurological evidence for nerve
      entrapment syndrome. Lack of conditions for a complex arthroscopic procedure
      (technique of visualisation, instrumentation, knowledge of specific
      neuroanatomy). SURGICAL TECHNIQUE: Diagnostic arthroscopy,
      decompression/resection of ganglion cyst. Visualisation and decompression of
      nerve. Detection and fixation of concomitant pathologies. POSTOPERATIVE
      TREATMENT: Immobilisation in sling during the day after the operation. Actively
      assisted and active mobilisation of shoulder controlled by discomfort level.
      Manual lymph drainage starting on postoperative day 1. Sling and further
      rehabilitation according to treatment of concomitant lesions.

PMID- 24924509
TI  - [Use of a pediculed pectoralis major flap for the treatment of septic arthritis
      of the sternoclavicular joint].
AB  - OBJECTIVE: Closure of the wound defect with a pedicled pectoralis major muscular
      flap after successful surgical treatment of septic arthritis of the
      sternoclavicular joint (SCJ). INDICATIONS: Defect of the thoracic wall after
      septic arthritis of the SCJ. CONTRAINDICATIONS: Persistent infection of bony or
      soft tissue structures; persistent septicemia; persistent mediastinitis. SURGICAL
      TECHNIQUE: After successful treatment of the local infection and radical
      debridement of the wound, the incision is expanded parallel to the clavicle and
      to the sternum. The neurovascular pedicled pectoralis flap is mobilized and a
      resection of the muscular attachment at the humerus is performed. Finally, the
      flap is rotated at the pedicle and attached to the defect zone. POSTOPERATIVE
      MANAGEMENT: Anticoagulation with low molecular weight heparin and possibly
      aspirin (100 mg/day); short-term immobilization of the involved upper extremity.
      Avoidance of major weight bearing for a period of 6 weeks. RESULTS: Over a period
      of 4 years, 18 patients suffering from septic arthritis of the SCJ underwent
      surgical treatment. Of these, 9 patients were treated with pedicled muscular
      flap. In all patients, uneventful wound healing was observed with no further
      revision operations being required. The functional and optical results were
      satisfactory.

PMID- 24924510
TI  - [Transfer of the coracoid process in recurrent anterior instability of the
      shoulder joint. The arthroscopic Latarjet procedure].
AB  - OBJECTIVE: Full arthroscopic treatment of severe anterior shoulder instability
      due to glenoid bone loss, Hill-Sachs lesion and irreparable ligament damage.
      INDICATIONS: Recurrent anterior dislocations or subluxations, previously failed
      Bankart repairs; patients with anterior glenoid bone loss, Hill-Sachs defect;
      patients with irreparable damage to soft tissues of labrum, capsule and
      ligaments; patients with chronic humeral avulsion of glenohumeral ligament (HAGL
      lesion); combinations of lesions above; young contact sport athletes, where
      Bankart repairs have high failure rates. CONTRAINDICATIONS: Presence of
      (arthroscopically confirmed) good preconditions for Bankart repair: good quality
      of labrum, capsule and ligament, labrum still present, no or minimal bone loss of
      glenoid, no engaging Hill-Sachs. Lack of requirements for complex arthroscopic
      procedure (e.g., special instruments and skills). SURGICAL TECHNIQUE: Diagnostic
      arthroscopy. Removal of anterosuperior and superior capsule, middle glenohumeral
      ligament, anterior labrum. Preparation of glenoid neck, debridement. Opening of
      rotator interval. Preparation of coracoid process and conjoint tendons.
      Subdeltoid preparation of anterior coracoid with arthroscope moved to
      anterolateral portal. Tenotomy of pectoralis minor. Arthroscopic split of
      subscapularis tendon via deep anteromedial portal. Predrilling of 2 holes through
      coracoid, insertion of 2 special washers into predrilled holes ("top hats").
      Arthroscopic osteotomy of coracoid at base. Mounting of coracoid to special
      coracoid cannula. Manipulation of coracoid/conjoint tendon through subscapularis
      to glenoid neck, prefixation with wires. Fixation of coracoid after drilling with
      cannulated special screws. POSTOPERATIVE MANAGEMENT: Immobilization in a sling on
      postoperative day 1; pain-controlled active range of motion without limit
      starting postoperative day 2. Sling during the night for 4 weeks. RESULTS:
      Between 2007 and June 2013, 210 operations were performed. No intraoperative
      conversion to open operative technique. Revision required in 10 patients with
      postoperative complications. No intraoperative or neurovascular complications.

PMID- 24924511
TI  - [Arthodesis of the proximal and distal interphalangeal joint].
AB  - OBJECTIVE: Elimination of the fixed lesser toe deformity by arthrodesis of the
      proximal or distal interphalangeal joints (PIP and DIP, respectively).
      INDICATIONS: Painful fixed deformity. PIP joint: fixed hammer toe or clawtoe. DIP
      joint: fixed mallet toe. Relative indication: flexible hammer toe, clawtoe or
      mallet toe. CONTRAINDICATIONS: General operative contraindications. Relative
      contraindications also include severe deformities affecting the
      metatarsophalangeal (MTP) joint, for which the arthrodesis should combine an
      operative procedure of the MTP joint. SURGICAL TECHNIQUES: PIP arthrodesis:
      Dorsal incision centered over the PIP joint, exposure of the PIP joint by
      transsecting the extensor tendon and joint capsule, release of the collateral
      ligaments, while carefully protecting the neurovascular bundles, resection of the
      head of the proximal phalanx and the articular surface of the middle phalanx. The
      arthrodesis should be stabilised in mild plantar flexion. The tip of the toe
      should have contact with the surface when the push up test is done. The
      arthrodesis technique depends on the implant used. The extensor tendon is sutured
      and the wound is closed. DIP arthrodesis: dorsal incision centered over the DIP
      joint, exposure of the DIP joint by transsecting the extensor tendon and joint
      capsule, release of the collateral ligaments, while carefully protecting the
      neurovascular bundles. Resection of the head of the middle phalanx and the
      articular surface of the distal phalanx. The arthrodesis should be stabilised in
      straight position. The arthrodesis technique depends on the implant used. The
      extensor tendon is sutured and the wound is closed. POSTOPERATIVE MANAGEMENT:
      Postoperative full weight bearing for 3-6 weeks, depending on the arthrodesis
      technique used. RESULTS: Stabilisation of the toe with adequate alignment is
      achieved by arthrodesis of the affected joint. In general, digital fusion of the
      fixed lesser toe pathology shows a high subjective satisfaction rate among the
      patients, although the rate of pseudarthrosis in attempted PIP or DIP arthrodesis
      is quite high. Major reasons for postoperative dissatisfaction were swelling,
      wound necrosis, pin infection, floating toe, shortening and angulation of the
      toe.

PMID- 24924512
TI  - Pilot study of a novel tool for input-free automated identification of transition
      zone prostate tumors using T2- and diffusion-weighted signal and textural
      features.
AB  - PURPOSE: To present results of a pilot study to develop software that identifies
      regions suspicious for prostate transition zone (TZ) tumor, free of user input.
      MATERIALS AND METHODS: Eight patients with TZ tumors were used to develop the
      model by training a Naive Bayes classifier to detect tumors based on selection of
      most accurate predictors among various signal and textural features on T2
      weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Features
      tested as inputs were: average signal, signal standard deviation, energy,
      contrast, correlation, homogeneity and entropy (all defined on T2WI); and average
      ADC. A forward selection scheme was used on the remaining 20% of training set
      supervoxels to identify important inputs. The trained model was tested on a
      different set of ten patients, half with TZ tumors. RESULTS: In training cases,
      the software tiled the TZ with 4 * 4-voxel "supervoxels," 80% of which were used
      to train the classifier. Each of 100 iterations selected T2WI energy and average
      ADC, which therefore were deemed the optimal model input. The two-feature model
      was applied blindly to the separate set of test patients, again without operator
      input of suspicious foci. The software correctly predicted presence or absence of
      TZ tumor in all test patients. Furthermore, locations of predicted tumors
      corresponded spatially with locations of biopsies that had confirmed their
      presence. CONCLUSION: Preliminary findings suggest that this tool has potential
      to accurately predict TZ tumor presence and location, without operator input.

PMID- 24924513
TI  - Robotic intracorporeal urinary diversion: technical details to improve time
      efficiency.
AB  - OBJECTIVES: To present time-efficiency data during our initial experience with
      intracorporeal urinary diversion and technical tips that may shorten operative
      time early in the learning curve. PATIENTS AND METHODS: Data were analyzed in the
      initial 37 consecutive patients undergoing robotic radical cystectomy and
      intracorporeal urinary diversion in whom detailed stepwise operative time data
      were available. Median age was 65 years and median body mass index was 27.
      Neoadjuvant chemotherapy was administered in 6 patients and 11 patients had
      clinical evidence of T3 or lymph node-positive disease. Each component of the
      operation was subdivided into specific steps and operative time for each step was
      prospectively recorded. Peri-operative and follow-up data up to 90 days and final
      pathological data were recorded. RESULTS: All procedures were completed
      intracorporeally and robotically without need for conversion to open surgery or
      extracorporeal diversion. Median total operative time was 387 vs 386 minutes
      (p=0.2) and median total console time was 361 vs 295 minutes (p<0.007) for
      orthotopic neobladder and ileal conduit, respectively. Median time for radical
      cystectomy was 77 minutes, extended pelvic lymph node dissection was 63 minutes,
      and diversion was 111 minutes (ileal conduit 92 minutes and orthotopic neobladder
      124 minutes). Median estimated blood loss was 250 mL, and median hospital stay
      was 9 days. High grade (Clavien grade 3-5) complications at 30 and 90 days follow
      up were recorded in 6 (16%) and 9 (24%) patients, respectively. Over a median
      follow-up of 16 months, 12 (32%) patients experienced disease recurrence and 9
      (24%) died from bladder cancer. These correspond to 1-year recurrence-free and
      overall survival of 64% and 70%, respectively. CONCLUSIONS: Intracorporeal
      urinary diversion following robotic radical cystectomy can be safely performed
      and reproducible in a time-efficient manner even during the early learning curve.

PMID- 24924514
TI  - Controlled hierarchical assembly of spider silk-DNA chimeras into ribbons and
      raft-like morphologies.
AB  - Spider silk-DNA conjugates comprising the recombinant spider silk protein
      eADF4(C16) and short oligonucleotides were arranged in a linear antiparallel and
      parallel as well as in a branched manner via designed complementarity of the DNA
      moieties. After cross-beta fibril self-assembly, temperature-induced annealing of
      the DNA moieties triggered fibril association into ribbons, composed of aligned
      nanofibrils, and rafts composed of ribbons ordered into sharply bordered, squared
      fibrous microstructures. The formation of the superstructures was clearly
      dependent on the individual silk-DNA conjugate. A combination of 5'-conjugated
      silk moieties via complementary nucleic acids enhanced fibril association,
      whereas mixing complementary 5'- and 3'-silk conjugates inhibited the formation
      of higher-order structures. 

PMID- 24924515
TI  - Mixed methods research - the best of both worlds?
AB  - INTRODUCTION: There has been a bias towards quantitative research approaches
      within manual therapy, which may have resulted in a narrow understanding of
      manual therapy practice. The aim of this Masterclass is to make a contribution to
      the expansion of methodologies used in manual therapy enquiry by discussing mixed
      methods research (MMR), a methodology which utilises both qualitative and
      quantitative methods within a single study in order to provide more comprehensive
      insights. PURPOSE: To review rationales for MMR, as well as some of the common
      design options and potential difficulties. The paper also discusses theoretical
      frameworks that have been used to underpin qualitative and quantitative research,
      and ongoing debates about the possibility of combining them. IMPLICATIONS:
      Complexities associated with health and manual therapy cannot always be
      investigated satisfactorily by using a single research method. Some issues
      require a more comprehensive understanding, which may be provided by combining
      the strengths of quantitative and qualitative methods in a mixed methods study.

PMID- 24924516
TI  - A piggyBac transposon- and gateway-enhanced system for efficient BAC
      transgenesis.
AB  - BACKGROUND: Bacterial artificial chromosomes (BACs) have become increasingly
      popular vectors for making transgenic mice, as they are able to carry large
      genomic DNA fragments that in many cases are needed to reproduce the endogenous
      gene expression pattern. However, the efficiency of BAC transgenesis is generally
      low, and gene transfer to BAC vectors by recombination-mediated engineering
      (recombineering) is time-consuming and technically demanding. RESULTS AND
      CONCLUSIONS: We present an enhanced system, comprising a BAC vector retrofitted
      with piggyBac DNA transposon elements and attL (Gateway) docking sites, that
      obviates these problems. Using this system, a gene-of-interest (such as a
      reporter gene) is transferred to the vector in a one-step in vitro reaction, and
      piggyBac transposition mediates transgene integration at high efficiency when
      microinjected into mouse zygotes with piggyBac transposase mRNA. We establish
      proof-of-principle for this system using a Wilms tumour-1 (Wt1) BAC to drive
      expression of an mCherry-2A-EGFP (RG) reporter gene, which yielded transgenic
      mice at a frequency of 33%, and recapitulated endogenous WT1 expression in
      developing gonads, kidneys and heart. The system we describe is applicable to any
      BAC transgenesis strategy.

PMID- 24924517
TI  - Electrospray ionization mechanisms for large polyethylene glycol chains studied
      through tandem ion mobility spectrometry.
AB  - Ion mobility mass spectrometry (IMS-MS) is used to investigate the abundance
      pattern, n(z)(m) of poly-(ethyleneglycol) (PEG) electrosprayed from
      water/methanol as a function of mass and charge state. We examine n(z)(m)
      patterns from a diversity of solution cations, primarily dimethylammonium and
      triethylammonium. The ability of PEG chains to initially attach to various
      cations in the spraying chamber, and to retain them (or not) on entering the MS,
      provide valuable clues on the ionization mechanism. Single chains form in highly
      charged and extended shapes in most buffers. But the high initial charge they
      hold under atmospheric pressure is lost on transit to the vacuum system for large
      cations. In contrast, aggregates of two or more chains carry in all buffers at
      most the Rayleigh charge of a water drop of the same volume. This shows either
      that they form via Dole's charge residue mechanism, or that highly charged and
      extended aggregates are ripped apart by Coulombic repulsion. IMS-IMS experiments
      in He confirm these findings, and provide new mechanistic insights on the
      stability of aggregates. When collisionally activated, initially globular dimers
      are stable. However, slightly nonglobular dimers projecting out a linear appendix
      are segregated into two monomeric chains. The breakup of a charged dimer is
      therefore a multi-step process, similar to the Fenn-Consta polymer extrusion
      mechanism. The highest activation barrier is associated to the first step, where
      a short chain segment carrying a single charge escapes (ion-evaporates) from a
      charged drop, leading then to gradual field extrusion of the whole chain out of
      the drop.

PMID- 24924518
TI  - Direct analysis of large living organism by megavolt electrostatic ionization
      mass spectrometry.
AB  - A new ambient ionization method allowing the direct chemical analysis of living
      human body by mass spectrometry (MS) was developed. This MS method, namely
      Megavolt Electrostatic Ionization Mass Spectrometry, is based on electrostatic
      charging of a living individual to megavolt (MV) potential, illicit drugs, and
      explosives on skin/glove, flammable solvent on cloth/tissue paper, and volatile
      food substances in breath were readily ionized and detected by a mass
      spectrometer. 

PMID- 24924519
TI  - Protein kinase a phosphorylates Dlx3 and regulates the function of Dlx3 during
      osteoblast differentiation.
AB  - Protein kinase A (PKA), a serine/threonine kinase, regulates bone formation, and
      enhances Bone morphogenetic protein (BMP)-induced osteoblast differentiation.
      However, the mechanisms of how PKA controls the cellular response to BMP are not
      well known. We investigated the effects of modulating PKA activity during BMP2
      induced osteoblast differentiation, and found that PKA regulates the function of
      Dlx3. Dlx3 plays crucial roles in osteoblast differentiation and it is expressed
      in most skeletal elements during development. We found that PKA activation
      increases BMP2-induced expression of Dlx3 protein, and enhances the protein
      stability, DNA binding, and transcriptional activity of Dlx3. In addition, PKA
      activation induces the phosphorylation of Dlx3 at consensus PKA phosphorylation
      target site(s). Lastly, substitution of serine 10 in Dlx3 to alanine
      significantly reduces, if not completely abolishes, the phosphorylation of Dlx3
      and the regulation of Dlx3 function by PKA. These results suggest that Dlx3 is a
      novel target of PKA, and that PKA mediates BMP signaling during osteoblast
      differentiation, at least in part, by phosphorylating Dlx3 and modulating the
      protein stability and function of Dlx3.

PMID- 24924520
TI  - "Overrepresentation of T17 cells in the peripheral blood of psoriatic patients is
      not confined to the skin-homing T cell subset".

PMID- 24924521
TI  - Anti-graying effect of the extract of Pueraria thunbergiana via upregulation of
      cAMP/MITF-M signaling pathway.

PMID- 24924523
TI  - Inherent costs and interdependent impacts of infrastructure network resilience.
AB  - Recent studies in system resilience have proposed metrics to understand the
      ability of systems to recover from a disruptive event, often offering a
      qualitative treatment of resilience. This work provides a quantitative treatment
      of resilience and focuses specifically on measuring resilience in infrastructure
      networks. Inherent cost metrics are introduced: loss of service cost and total
      network restoration cost. Further, "costs" of network resilience are often shared
      across multiple infrastructures and industries that rely upon those networks,
      particularly when such networks become inoperable in the face of disruptive
      events. As such, this work integrates the quantitative resilience approach with a
      model describing the regional, multi-industry impacts of a disruptive event to
      measure the interdependent impacts of network resilience. The approaches
      discussed in this article are deployed in a case study of an inland waterway
      transportation network, the Mississippi River Navigation System. 

PMID- 24924522
TI  - Effects of soyabean meal- or whey-based diets on lipid metabolism in weaned
      piglets.
AB  - The present study aimed to test the hypothesis that dietary protein source
      influences lipid metabolism-related parameters weaned piglets. The effects of
      soyabean meal (SB) and whey proteins (WP) on gene expression of several genes
      involved in the lipogenic process in liver, visceral (VAT) and subcutaneous (SAT)
      adipose tissues, plasma insulin concentration and fatty acid (FA) profile were
      investigated in 18 weaned piglets. Weaned piglets were fed one of two diets
      containing either SB or WP as the main protein source. Following a 10-h fasting
      period, plasma insulin concentration and FA profile were assessed at 56 and 72
      days of age, whereas gene expression in liver, VAT and SAT was assessed at 72
      days of age. Plasma insulin concentration was not affected by diet, although it
      was 40% lower in SB fed pigs. The SB pigs had lower 14:0 (p < 0.01) and higher
      18:3n-3 (p < 0.001) levels in plasma in comparison with WP pigs. However, these
      changes were attributed to background differences in the dietary FA profile and
      not to a direct protein source effect. Gene expression of sterol regulatory
      element-binding protein 1 (SREBP-1) in liver and VAT were lower (p < 0.01 and p <
      0.05, respectively) in SB compared to WP fed piglets, but no differences occurred
      in SAT. No changes were observed in sterol regulatory element-binding protein 2,
      liver X receptor, peroxisome proliferator-activated receptors alpha and gamma and
      plasminogen activator inhibitor 1 mRNA levels, either in liver or in adipose
      tissues. In conclusion, dietary protein source, accompanied likely by side
      alterations in the dietary composition, affects lipid metabolism in pigs through
      the downregulation of SREBP-1, which is a crucial determinant of lipogenic
      process.

PMID- 24924524
TI  - Vasorelaxant effects of Cerebralcare Granule(r) are mediated by NO/cGMP pathway,
      potassium channel opening and calcium channel blockade in isolated rat thoracic
      aorta.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cerebralcare Granule (CG), one of the famous
      classical recipes in traditional Chinese medicine, is developed from the
      "Decoction of Four Drugs". It has been used for treatment of cerebrovascular
      related diseases, such as hypertension. It is well known that vasodilatation
      plays a very important role in hypertensive. Despite the popular medicinal use of
      CG, little data was available to its activity and mechanism involved in
      vasodilatation. Therefore, we aimed to investigate the vasorelaxant effects of CG
      on isolated rat thoracic aorta so as to assess some of the possible mechanisms.
      The present study was performed to examine the vasodilative activity of CG and
      its mechanisms in isolated rat thoracic aorta. MATERIALS AND METHODS: CG was
      studied on isolated rat thoracic aorta in vitro, including endothelium-intact and
      endothelium-denuded aortic rings. In present study, specific inhibitors including
      NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), cyclooxygenase
      (COX) inhibitor indomethacin (INDO), non-selective K+ channel inhibitor
      tetraethylammonium chloride (TEA), Kir channel inhibitor BaCl2, KATP channel
      inhibitor Glibenclamide (Gli) and cholinergic receptor antagonist atropine were
      used, they were added 20 min before NE contraction and then added CG-induced
      vasodilation. RESULTS: Removal of endothelium or pretreatment of aortic rings
      (intact endothelium) with L-NAME (0.1 mM) or INDO (0.01 mM) significantly blocked
      the CG induced relaxation. Pretreatment with the non-selective K+ channel
      inhibitor TEA (1 mM), or the Kir channel inhibitor BaCl2 (0.1 mM), neither of
      them had no influence on the CG-induced response (p>0.05). However, pretreatment
      with the KATP channel inhibitor Gli (0.01 mM) produced significant inhibition on
      the CG-induced response (p<0.01). Besides, CG also inhibited the contraction
      triggered by NE in endothelium-denuded rings in Ca2+-free medium. CG (0.4, 0.8
      and 3.2 mg/mL) produced rightward parallel displacement of CaCl2 curves and
      reduced the maximum contraction induced by 30 mM CaCl2 to 31.1+/-9.3%, 18.8+/
      6.9% and 9.4+/-4.5%, respectively. The relaxation, induced by CG on endothelium
      intact rat aortic rings pre-contracted with NE, was significantly attenuated in
      the presence of atropine (EC50=3.7 mg/mL, p<0.01). CONCLUSIONS: Our results
      suggest that CG induces relaxation in rat aortic rings through an endothelium
      dependent pathway mediated by NO/cGMP pathway and an endothelium-independent
      pathway involving blockade of Ca2+ channels, inhibition of Ca2+ mobilization from
      intracellular stores, opening of KATP channel. In addition, the muscarinic
      receptor stimulation is also one of the vasorelaxant mechanisms.

PMID- 24924525
TI  - What could Nintedanib (BIBF 1120), a triple inhibitor of VEGFR, PDGFR, and FGFR,
      add to the current treatment options for patients with metastatic colorectal
      cancer?
AB  - Increasing knowledge of the pro-angiogenic processes involved in the progression
      of metastatic colorectal cancer (mCRC) has resulted in the clinical development
      of several anti-angiogenic agents, with bevacizumab currently being the only
      approved agent for mCRC. Nintedanib (BIBF 1120) has been shown to block the
      vascular endothelial growth factor receptor (VEGFR), the platelet-derived growth
      factor receptor (PDGFR), and the fibroblast growth factor receptor (FGFR). By
      targeting FGFR signaling, nintedanib may overcome resistance to previous anti
      VEGF treatments, and may represent a better approach in patients with high basal
      levels of circulating FGFs. In this article, the angiogenic mechanisms implicated
      in mCRC are reviewed (focusing on the signaling pathways activated by VEGFR,
      PDGFR, and FGFR), along with the clinical data for nintedanib in the context of
      other anti-angiogenic tyrosine kinase inhibitors under clinical development for
      mCRC. Biomarkers that could predict response to nintedanib are also discussed. 

PMID- 24924526
TI  - The prevalence, comorbidity and risks of prolonged grief disorder among bereaved
      Chinese adults.
AB  - Few epidemiological studies have investigated prolonged grief disorder (PGD) in
      the general population of Asian countries, including China. The aim of this study
      was to explore the rates and risks of PGD, and the association between PGD, post
      traumatic stress disorder (PTSD), depression and anxiety in bereaved Chinese
      adults. The PG-13, PTSD Checklist-Civilian Version (PCL-C), Zung Self-Rating
      Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) were administered
      to 445 subjects. Prevalence within the general population of China was 1.8%
      (i.e., 8/445). Among the eight subjects who met the PGD diagnosis, 75%, 87.5% and
      75% scored above the cut-off point on the PCL-C, SDS and SAS, respectively,
      although a portion remained free from comorbidity. ANOVA, correlation analysis
      and stepwise multiple regression analysis demonstrated that kinship to deceased,
      age of the deceased, religion belief and cause of death were predictive of
      prolonged grief. A small proportion of bereaved persons may exhibit PGD. There is
      a substantial but far from complete overlap between PGD and the other three
      diagnoses. Bereaved parents and the widowed have high risk of PGD. These findings
      highlight the need for prevention, diagnosis and treatment for PGD patients. 

PMID- 24924527
TI  - Distribution analyses of acquired melanocytic naevi on the trunk.
AB  - Acquired melanocytic naevi (AMN) are a well-known risk factor for the development
      of melanoma. Whereas previous studies have reviewed AMN distributions on
      individual body sites, the clinical distribution of AMN on the adult trunk has
      not been thoroughly investigated. We studied 40 participants with 1,282 naevi >5
      mm, of which 781 were located on the trunk. Remarkably, 70% of these truncal
      naevi were located on the back and we produced a continuous mathematical
      description of decreasing naevus frequency moving dorsolaterally from the back
      midline. Furthermore we found that for both sexes the mean naevus size was larger
      on the front as well as on the lower trunk. This distinct pattern, whilst
      probably being unwritten knowledge (in the dermatology domain), has not been
      discussed before.

PMID- 24924528
TI  - Note to the readers.

PMID- 24924531
TI  - Red-green-blue fluorescent hollow carbon nanoparticles isolated from
      chromatographic fractions for cellular imaging.
AB  - An as-synthesised hollow carbon nanoparticle (HC-NP) sample has been proved to be
      a relatively complex mixture, and its complexity can be reduced significantly by
      high-performance liquid chromatography. An unprecedented reduction in such
      complexity can reveal fractions of HC-NP with unique luminescence properties.
      While the UV-vis absorption profile for the HC-NP mixture is featureless, the HC
      NP fractions do possess unique absorption bands and specific emission
      wavelengths. The HC-NP fractions are fully anatomised by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry, displaying their
      fragmentation mass ion features. The shell thickness and crystal lattices of the
      selected HC-NP fractions are determined as 6.13, 8.31, 2.22, and 8.66 nm, and
      0.37, 0.35, 0.33, and 0.32 nm by transmission electron microscopy, respectively.
      The fractionated HC-NP show profound differences in emission quantum yield,
      allowing for brighter HC-NP to be isolated from an apparent low quantum yield
      mixture. Finally, red, green and blue emissive HC-NP are isolated from the as
      synthesised HC-NP sample. They show good photostability and have been
      demonstrated to be excellent probes for cellular imaging. 

PMID- 24924530
TI  - Body size across the life course and risk of premenopausal and postmenopausal
      breast cancer in Black women, the Carolina Breast Cancer Study, 1993-2001.
AB  - BACKGROUND: It is believed that greater adiposity is associated with reduced risk
      of breast cancer in premenopausal but increased risk in postmenopausal women.
      However, few studies have evaluated these relationships among Black women or
      examined anthropometric measures other than near-diagnosis body mass index (BMI).
      PURPOSE: This study investigated associations between measures of body size
      across the life course and breast cancer risk among Black and White women living
      in the US South. METHODS: We used data from the Carolina Breast Cancer Study, a
      population-based case-control study of invasive breast cancer in North Carolina
      women aged 20-74 years. We assessed nine body size variables, including age 10
      relative weight; age 18 BMI; adult weight gain; "reference" BMI 1 year before
      interview; and post-diagnosis measured BMI and abdominal obesity measures.
      RESULTS: Among premenopausal Whites, heavier childhood relative weight was
      associated with decreased cancer risk [odds ratio (OR) 0.48 95 % confidence
      interval 0.33-0.70]. Among premenopausal Blacks, greater adult waist
      circumference and waist-to-hip ratio (WHR) were associated with increased risk
      [waist OR 1.40 (1.00-1.97) and high tertile WHR OR 2.03 (1.29-3.19)], with
      associations for WHR in a similar direction in Whites. Among postmenopausal
      women, recalled body size was not associated with risk, except for increased risk
      associated with adult weight gain among White non-hormone therapy users. ER/PR
      status and hormone therapy use also modified other associations. DISCUSSION: In
      this population, greater adult BMI was not associated with increased breast
      cancer risk, but some measures of early-life body size and abdominal obesity were
      associated with risk.

PMID- 24924533
TI  - Division of parental care and reproductive success in the zebra finch
      (Taeniopygia guttata ).
AB  - Variation in reproductive success among pairs of Zebra finches (Taeniopygia
      guttata ), bred in captivity under time- rather than energy-limited conditions,
      arose primarily because of differences in number of clutches per reproductive
      bout. Division of parental care between mates during the time-constrained
      incubation phase, rather than the fledging phase, affected their fitness and
      future behavior. Pairs where the males assumed a greater fraction of the pooled
      incubation time were more likely to breed together again than pairs where males
      did not share in this activity as equally. In addition, males remated with
      familiar mates increased their time investment in incubation. 

PMID- 24924532
TI  - A series of severe necrotising soft-tissue infections in a regional centre in
      Sweden.
AB  - BACKGROUND: Necrotising soft-tissue infections (NSTIs) are rare conditions with
      high morbidity and mortality. Patients with NSTIs are often transferred to
      tertiary hospitals, but the question of whether the potential benefits of highly
      specialised care outweigh the risks associated with inter-hospital transfers has
      been raised. METHODS: Prospective study including all patients with NSTIs treated
      at the intensive care unit at Sahlgrenska University Hospital/East between
      January 2008 and December 2011. RESULTS: Twenty-nine patients with NSTIs were
      identified. Their median age was 54 years and 69% were men. Major co-morbidities
      were present in 45%. Seventeen patients (59%) were referred from other hospitals.
      Only 33% of the patients were correctly diagnosed or suspected of having NSTIs in
      the emergency department. Group A Streptococcus was the most common
      microbiological finding (41%), followed by Enterobacteriaceae (17%). The median
      time from hospitalisation to the first dose of antibiotics was 6 h and the median
      time to primary surgery was 16 h. Hyperbaric oxygen therapy was given to 86%, and
      intravenous immunoglobulin was given in 52% of the cases. The 30-day mortality
      was 14% (4/29). The times to the first dose of antibiotics, intensive care unit
      admission and primary surgery did not differ between transferred and directly
      admitted patients, and there was no difference in outcome between the groups.
      CONCLUSIONS: Patients with NSTIs develop severe local and systemic symptoms and
      require extremely resource-demanding hospitalisation. Inter-hospital transfer was
      not associated with a delay in key interventions and could not be identified as a
      risk factor for adverse outcome.

PMID- 24924534
TI  - Position learning in chicks.
AB  - Chicks were trained to discriminate between two similar boxes according to their
      "relative" (i.e. in relation to each other) or "absolute" (i.e. in relation to
      the cage or other features of the environment) position. Results showed: (a) when
      the boxes were placed close together, learning on the basis of their relative
      position was much more rapid than on the basis of their absolute position; (b)
      when the boxes were placed further apart, learning required more trials but
      differences between the two training methods were reduced. 

PMID- 24924535
TI  - New data on communication behaviour between the young child and his pet dog.
AB  - A systematic investigation of communication behaviour between 2-to-5 year old
      children and their pet dogs (N=18), from video films shot in the home, shows that
      children take the initiative in communication more often, and that they seek more
      body contact with their dog. Different characteristics of the children such as
      age, family size and different characteristics of the dog such as size and sex
      are significantly correlated (p<.01 or p<.05) with the quantity of communications
      and with the different types of child behaviour in relation to the dog (stroking,
      hitting, etcz.sfnc;). This preliminary report leads to suggestions for further
      investigations of the data. 

PMID- 24924536
TI  - Does neophobia necessarily imply fear or anxiety?
AB  - Mice which had the opportunity to move around freely in simultaneously presented
      novel and familiar environments, did not display significant changes in plasma
      corticosterone levels nor in autonomic responses. In contrast, the signs of
      anxiety only appeared when mice were unable to regulate their own approach
      towards novelty, by preventing them from returning to their familiar compartment
      once they had freely entered the unfamiliar one, or by placing them physically
      into the novel compartment. These results demonstrate that contrary to the view
      generally encountered in the literature, anxiety, or fear, is not induced by
      novelty per se but when animals are artificially confronted novel stimuli and
      prevented from displaying normal neophobic responses. 

PMID- 24924537
TI  - Responses to novelty in staggerer mutant mice.
AB  - Responses to novelty in normal C57BL/6 and staggerer mutant mice were recorded.
      The normal mice confronted a novel object in their familiar environment showed
      avoidance and burying responses while the staggerer mutant mice contacted it.
      When given the opportunity to move around freely in simultaneously presented
      novel and familiar environments, the mutant mice more quickly entered the novel
      areas than normal animals. these data reveal a significant decrease in the
      neophobic components of the neotic behaviour in the staggerer mice. However,
      since the mutant mice did not show a locomotor deficit, the impairment of
      neophobia seems not to be due to the gait abnormalities of these animals. The
      results support the view that the cerebellum may contribute to the organization
      of complex behaviours. 

PMID- 24924538
TI  - Adaptation to cold swim stress-induced hypothermia: Absence of Pavlovian
      conditional tolerance.
AB  - Mice subjected to cold swim stress developed pronounced hypothermia. Exposure to
      warm water swim, however, had little or no effect on body temperature. After
      repeated exposure to cold swim, the stress-induced hypothermia was attenuated.
      The finding that cold swim resulted in hypothermia, whereas warm swim had no
      effect in this respect, provided a useful experimental design by which to assess
      the role of conditioning factors in the adaptation to the thermic effects of cold
      swim. In two subsequent experiments, mice received cold swim either in a familiar
      environment or in a novel environment. Adaptation to the thermic effects of cold
      swim was observed when mice were tested in the distinctive environment,
      regardless of the environmental cues previously paired with repeated exposure to
      the cold swim stress. These findings suggest that contextual cues were not of
      primary importance in the development of tolerance to the thermic effects of cold
      swim stress. 

PMID- 24924539
TI  - Sex differences during initial social contact in the degu (Octodon degus ).
AB  - The degu is a hystricomorph rodent endemic to South America. Initial social
      interactions between like-sexed pairs in a neutral area were found to be heavily
      influenced by sex-class membership. Twelve of fifteen behavioral categories were
      differentiated on the basis of sex-class. Descriptive factor loadings indicated
      that social contact was facilitated in females via olfactory investigation. In
      males, social avoidance or spacing behaviors were characteristic. In both sexes,
      scent marking and olfactory investigation was prevalent. These data serve to
      expand our knowledge of the behavior of this social rodent, and to document the
      sexual dimorphism evident in early social activities. 

PMID- 24924540
TI  - Temporal spacing of signals in communication, studied in weakly-electric mormyrid
      fish (teleostei, pisces).
AB  - Both the shape of the electric pulses and their rhythm of emission serve in
      communication in weakly-electric mormyrid fish. Because the pulses emitted by a
      given individual show very little variability, whereas the rhythm of emission is
      highly variable, the mormyrids electric emission can be considered to be the
      repetition according to various temporal spacings of the same signal. It allows
      therefore to study the role of the temporal spacing of signals in communication.
      The temporal spacing of the pulses could serve at a global level, in allowing the
      effects of consecutive pulses to summate. It could also be itself part of higher
      order signals. In order to discriminate between these two possibilities,
      sequences of a conspecific's electric emission were played back to the mormyrid
      fish Gnathonemus petersii . The importance of the temporal spacing of the pulses
      at a global level was investigated by comparing the effects of (a)- 3 sequences
      of similar overall rate of discharge, (b)- 2 sequences of same rate of discharge
      plus same composition in interpulse intervals. Sequences of similar mean
      frequency (14 +/- 1 Hz) elicited different responses, showing they had different
      communicative values. Sequences having both the same interval composition and the
      same mean frequency elicited reactions which presented similarities, showing that
      the communicative value of the electric emission does nevertheless depend on the
      spacing of the pulses at a global level. The presence of higher order signals was
      investigated by testing the importance of the serial ordering of the intervals in
      electric emission. Randomisation of the intervals did alter the effect of a
      sequence, suggesting the existence of such signals. We showed that both the
      global composition in intervals and their serial ordering are relevant to
      electrocommunication in mormyrids. Thus, their communication system constitutes a
      useful model for the study of the transformation of sequences of simple signals
      into higher-order signals. 

PMID- 24924542
TI  - The incidence of genitourinary and gastrointestinal complications in open and
      endoscopic gynecologic cancer surgery.
AB  - OBJECTIVES: The purpose of this study was to examine the incidence of
      genitourinary and intestinal tract injuries in an effort to identify which
      factors might predispose a patient to developing one of these surgical
      complications. METHODS: We retrospectively evaluated the charts of gynecologic
      cancer patients who were treated at a single medical institution from January
      2002 to February 2011. The following study variables were noted for evaluation:
      age, BMI, cancer origin, disease recurrence, a history of pelvic surgery, surgery
      type, operative approach and injury classification (genitourinary or
      gastrointestinal). RESULTS: In our group of 1,618 patients, a total of 47 (2.9%)
      gastrointestinal and 18 (1.1%) genitourinary tract injuries were encountered.
      There were no intraoperative-related deaths but 2 patients expired 1 month after
      surgery. Logistic regression indicated that surgery type, undergoing an open
      procedure, cancerous involvement of the bowel or genitourinary tract and a
      history of pelvic surgery were significant predictors of operative injury
      occurrence [chi(2) (28) = 167.22; p < 0.001]. CONCLUSIONS: We ascertained a
      relatively low incidence of gastrointestinal and genitourinary complications.
      Nevertheless, undergoing an open procedure, a history of pelvic surgery and
      surgical involvement of the bowel or genitourinary tract were predictive of an
      increased risk for these aforementioned injuries.

PMID- 24924541
TI  - Cell activation and HIV-1 replication in unstimulated CD4+ T lymphocytes
      ingesting exosomes from cells expressing defective HIV-1.
AB  - BACKGROUND: A relevant burden of defective HIV-1 genomes populates PBMCs from HIV
      1 infected patients, especially during HAART treatment. These viral genomes,
      although unable to codify for infectious viral particles, can express viral
      proteins which may affect functions of host cells as well as bystander ones.
      Cells expressing defective HIV-1 have a lifespan longer than that of cells
      producing infectious particles. Hence, their interaction with other cell types,
      including resting lymphocytes, is expected to occur frequently in tissues where
      HIV actively replicates. We investigated the effects of the expression of a
      prototype of functionally defective HIV-1 on bystander, unstimulated CD4+ T
      lymphocytes. RESULTS: We observed that unstimulated human primary CD4+ T
      lymphocytes were activated and became permissive for HIV-1 replication when co
      cultivated with cells expressing a functionally defective HIV-1 (F12/Hut-78
      cells). This effect depended on the presence in F12/Hut-78 supernatants of
      nanovesicles we identified as exosomes. By inspecting the underlying mechanism,
      we found that ADAM17, i.e., a disintegrin and metalloprotease converting pro-TNF
      alpha in its mature form, associated with exosomes from F12/Hut-78 cells, and
      played a key role in the HIV-1 replication in unstimulated CD4+ T lymphocytes. In
      fact, the treatment with an inhibitor of ADAM17 abolished both activation and HIV
      1 replication in unstimulated CD4+ T lymphocytes. TNF-alpha appeared to be the
      downstream effector of ADAM17 since the treatment of unstimulated lymphocytes
      with antibodies against TNF-alpha or its receptors blocked the HIV-1 replication.
      Finally, we found that the expression of NefF12 in exosome-producing cells was
      sufficient to induce the susceptibility to HIV-1 infection in unstimulated CD4+ T
      lymphocytes. CONCLUSIONS: Exosomes from cells expressing a functionally defective
      mutant can induce cell activation and HIV-1 susceptibility in unstimulated CD4+ T
      lymphocytes. This evidence highlights the relevance for AIDS pathogenesis of the
      expression of viral products from defective HIV-1 genomes.

PMID- 24924544
TI  - On the search for the perfect mismatch!

PMID- 24924543
TI  - Computer-aided diagnosis improves detection of small intracranial aneurysms on
      MRA in a clinical setting.
AB  - BACKGROUND AND PURPOSE: MRA is widely accepted as a noninvasive diagnostic tool
      for the detection of intracranial aneurysms, but detection is still a challenging
      task with rather low detection rates. Our aim was to examine the performance of a
      computer-aided diagnosis algorithm for detecting intracranial aneurysms on MRA in
      a clinical setting. MATERIALS AND METHODS: Aneurysm detectability was evaluated
      retrospectively in 48 subjects with and without computer-aided diagnosis by 6
      readers using a clinical 3D viewing system. Aneurysms ranged from 1.1 to 6.0 mm
      (mean = 3.12 mm, median = 2.50 mm). We conducted a multireader, multicase, double
      crossover design, free-response, observer-performance study on sets of images
      from different MRA scanners by using DSA as the reference standard. Jackknife
      alternative free-response operating characteristic curve analysis with the figure
      of merit was used. RESULTS: For all readers combined, the mean figure of merit
      improved from 0.655 to 0.759, indicating a change in the figure of merit
      attributable to computer-aided diagnosis of 0.10 (95% CI, 0.03-0.18), which was
      statistically significant (F(1,47) = 7.00, P = .011). Five of the 6 radiologists
      had improved performance with computer-aided diagnosis, primarily due to
      increased sensitivity. CONCLUSIONS: In conditions similar to clinical practice,
      using computer-aided diagnosis significantly improved radiologists' detection of
      intracranial DSA-confirmed aneurysms of <=6 mm.

PMID- 24924545
TI  - Qualitative and quantitative performance of 18F-FDG-PET/MRI versus 18F-FDG-PET/CT
      in patients with head and neck cancer.
AB  - BACKGROUND AND PURPOSE: MR imaging and PET/CT are integrated in the work-up of
      head and neck cancer patients. The hybrid imaging technology (18)F-FDG-PET/MR
      imaging combining morphological and functional information might be attractive in
      this patient population. The aim of the study was to compare whole-body (18)F-FDG
      PET/MR imaging and (18)F-FDG-PET/CT in patients with head and neck cancer, both
      qualitatively in terms of lymph node and distant metastases detection and
      quantitatively in terms of standardized uptake values measured in (18)F-FDG-avid
      lesions. MATERIALS AND METHODS: Fourteen patients with head and neck cancer
      underwent both whole-body PET/CT and PET/MR imaging after a single injection of
      (18)F-FDG. Two groups of readers counted the number of lesions on PET/CT and
      PET/MR imaging scans. A consensus reading was performed in those cases in which
      the groups disagreed. Quantitative standardized uptake value measurements were
      performed by placing spheric ROIs over the lesions in 3 different planes.
      Weighted and unweighted kappa statistics, correlation analysis, and the Wilcoxon
      signed rank test were used for statistical analysis. RESULTS: kappa statistics
      for the number of head and neck lesion lesions counted (pooled across regions)
      revealed interreader agreement between groups 1 and 2 of 0.47 and 0.56,
      respectively. Intrareader agreement was 0.67 and 0.63. The consensus reading
      provided an intrareader agreement of 0.63. For the presence or absence of
      metastasis, interreader agreement was 0.85 and 0.70. The consensus reading
      provided an intrareader agreement of 0.72. The correlations between the maximum
      standardized uptake value in (18)F-FDG-PET/MR imaging and (18)F-FDG-PET/CT for
      primary tumors and lymph node and metastatic lesions were very high (Spearman r =
      1.00, 0.93, and 0.92, respectively). CONCLUSIONS: In patients with head and neck
      cancer, (18)F-FDG-PET/MR imaging and (18)F-FDG-PET/CT provide comparable results
      in the detection of lymph node and distant metastases. Standardized uptake values
      derived from (18)F-FDG-PET/MR imaging can be used reliably in this patient
      population.

PMID- 24924546
TI  - Brain metabolic mapping with MRS: A potent noninvasive tool for clinical
      diagnosis of brain disorders.

PMID- 24924547
TI  - Prediction of glioma recurrence using dynamic 18F-fluoroethyltyrosine PET.
AB  - BACKGROUND AND PURPOSE: Inter- and intratumor heterogeneity and the variable
      course of disease in patients with glioma motivate the investigation of new
      prognostic factors to optimize individual treatment. Here we explore the
      usefulness of standard static and more sophisticated dynamic (18)F
      fluoroethyltyrosine-PET imaging for the assessment of patient prognosis.
      MATERIALS AND METHODS: Thirty-four consecutive patients with untreated, first
      diagnosed, histologically proved glioma were included in this retrospective
      study. All patients underwent dynamic PET scans before surgery (+/- standard
      treatment) and were followed up clinically and by MR imaging. Static and dynamic
      tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated
      with progression-free survival. RESULTS: Twenty of 34 patients experienced
      progression, with a median progression-free survival of 28.0 +/- 11.1 months.
      Dynamic TTP was highly prognostic for recurrent disease, showing a strong
      correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11
      17.37; P < .001). Most interesting, this correlation also proved significant in
      the subgroup of low-grade glioma (hazard ratio, 5.347; 95% CI, 1.05-27.20; P =
      .044), but not when using established static imaging parameters, such as maximum
      tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade
      glioma subgroup, both dynamic and static parameters correlated with progression
      free survival. The best results were achieved by defining ROIs around "hot spots"
      in earlier timeframes, underlining the concept of intratumor heterogeneity.
      CONCLUSIONS: (18)F-fluoroethyltyrosine-PET can predict recurrence in patients
      with glioma, with dynamic analysis showing advantages over static imaging,
      especially in the low-grade subgroup.

PMID- 24924548
TI  - Neurointerventional research between 2003 and 2012: slow growth, high
      interdisciplinary collaboration, and a low level of funding.
AB  - BACKGROUND AND PURPOSE: Neurointerventional therapy of cerebrovascular disease is
      a greatly expanding field across many specialty disciplines. The goal of this
      study was to analyze the characteristics and trends of scientific publications
      that focused on neurointervention during the past decade. MATERIALS AND METHODS:
      A bibliometric evaluation of neurointerventional research published between 2003
      and 2012 was conducted by using the PubMed data base. Analyzed parameters
      included the year of publication, type of document, language of the article,
      topic, declared funding, country of origin, type of collaboration between
      disciplines, the first author's specialty, and subject category and the Impact
      Factor of the publishing journal. RESULTS: Between 2003 and 2012, a total of 2123
      articles were published, of which 1107 (52.1%) were original articles, 1948
      (91.8%) were written in English, 192 (9.0%) received funding, 661 (31.1%) were
      published by the United States, and 1060 (49.9%) resulted from interdisciplinary
      collaboration. Neurosurgery departments produced the most articles (n = 910,
      42.9%), followed by radiology (n = 747, 35.2%) and neurology (n = 270, 12.7%).
      The time-trend analysis in the number of publications demonstrated slow growth
      from 2003 to 2012, with an average annual growth rate of +6.0%. CONCLUSIONS: The
      fields of neurosurgery, radiology, and neurology have contributed substantially
      to neurointervention research. Slow growth, high interdisciplinary collaboration,
      and a low level of funding are peculiar characteristics of research in this
      field.

PMID- 24924549
TI  - The role of functional dopamine-transporter SPECT imaging in parkinsonian
      syndromes, part 2.
AB  - SUMMARY: The functional imaging technique most widely used in European clinics to
      differentiate a true parkinsonian syndrome from vascular parkinsonism, drug
      induced changes, or essential tremor is dopamine-transporter SPECT. This
      technique commonly reports dopamine-transporter function, with decreasing
      striatal uptake demonstrating increasingly severe disease. The strength of
      dopamine-transporter SPECT is that nigrostriatal degeneration is observed in both
      clinically inconclusive parkinsonism and early, even premotor, disease. In this
      clinical review (Part 2), we present the dopamine-transporter SPECT findings in a
      variety of neurodegenerative diseases, including multiple system atrophy,
      progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy
      bodies. The findings in vascular parkinsonism, drug-induced parkinsonism, and
      essential tremor are also described. It is hoped that this technique will be the
      forerunner of a range of routinely used, process-specific ligands that can
      identify early degenerative disease and subsequently guide disease-modifying
      interventions.

PMID- 24924550
TI  - Neuroimaging of diving-related decompression illness: current knowledge and
      perspectives.
AB  - Diving-related decompression illness is classified into 2 main categories:
      arterial gas embolism and decompression sickness. The latter is further divided
      into types 1 and 2, depending on the clinical presentation. MR imaging is
      currently the most accurate neuroimaging technique available for the detection of
      brain and spinal cord lesions in neurologic type 2 decompression sickness. Rapid
      bubble formation in tissues and the bloodstream during ascent is the basic
      pathophysiologic mechanism in decompression illness. These bubbles can damage the
      central nervous system through different mechanisms, namely arterial occlusion,
      venous obstruction, or in situ toxicity. Neuroimaging studies of decompression
      sickness have reported findings associated with each of these mechanisms: some
      typical results are summarized and illustrated in this article. We also review
      the limitations of previous work and make practical methodologic suggestions for
      future neuroimaging studies.

PMID- 24924551
TI  - The 3 pillars of health.

PMID- 24924552
TI  - Advancement of technology and its impact on urologists: release of the daVinci
      Xi, a new surgical robot.
AB  - The technology for robotic surgery continues to evolve. Robotic surgery has
      allowed us the opportunity to critically analyze outcomes and improve surgical
      technique both open and robotic. The new da Vinci Xi may allow us to do even more
      complex surgeries with minimally invasive techniques, but the true advantages
      remain to be seen. 

PMID- 24924553
TI  - Predictors of cancer-specific mortality after disease recurrence in patients with
      squamous cell carcinoma of the penis.
AB  - Disease recurrence occurs frequently after surgical treatment for squamous cell
      carcinoma of the penis (SCCp). We sought to determine prognostic factors that
      influence cancer-specific mortality (CSM) after disease recurrence in patients
      with SCCp. We performed a retrospective analysis of 314 patients who experienced
      disease recurrence after surgical treatment for SCCp between 1949 and 2012.
      Competing risk regression analysis addressed factors associated with CSM after
      SCCp recurrence. Median time from surgery to disease recurrence was 10.5 mo
      (interquartile range [IQR]: 5.9-21.3). Of the recurrences, 165 (53%), 118 (38%),
      and 31 (9.9%) were local, regional, or distant, respectively. Within a median
      follow-up of 4.5 yr (IQR: 2.0-6.5), 108 patients died of SCCp and 41 patients
      died of causes other than SCCp. Shorter time to disease recurrence was found to
      be significantly associated with a higher risk of CSM (p=0.0006). Lymph node
      metastasis at the time of initial treatment (subdistribution hazard ratio [SHR]:
      1.96; 95% confidence interval [CI] 1.23- 3.11; p=0.005) and regional recurrence
      (SHR: 4.14; 95% CI, 2.16-7.93; p<0.0001) or distant recurrence (SHR: 5.75; 95%
      CI, 2.59-12.73; p<0.0001) were associated with increased risk of CSM after
      disease recurrence. Inclusion of time to recurrence into risk stratification may
      help patient counseling and treatment planning. 

PMID- 24924554
TI  - Weighted versus unweighted Charlson score to predict long-term other-cause
      mortality in men with early-stage prostate cancer.
AB  - BACKGROUND: Clinicians need a simple yet accurate method to predict other-cause
      mortality to inform medical decision making for men with prostate cancer (PCa).
      OBJECTIVE: To compare weighted and unweighted Charlson Comorbidity Index scores
      in predicting long-term, other-cause mortality in men with early-stage PCa.
      DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 1482 men with
      early-stage PCa diagnosed in 1998-2004 at two Southern California Veterans
      Affairs medical centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subhazard
      ratios and cumulative incidence of other-cause mortality associated with weighted
      and unweighted Charlson scores, calculated by competing-risks regression
      accounting for cancer mortality, along with Harrell concordance index (C-index)
      values. RESULTS AND LIMITATIONS: Weighted and unweighted Charlson scores were
      identical in 88.6% of subjects (1313 of 1482 men) across all scores and in 91.7%
      of subjects (1359 of 1482 men) across scores of 0, 1, 2, and >=3. In competing
      risks analysis, hazards of other-cause mortality were similar when comparing
      weighted and unweighted scores. Men with weighted scores of 1, 2, and >=3 (vs. 0)
      had subhazard ratios of 2.3 (95% confidence interval [CI], 1.6-3.2), 4.1 (95% CI,
      2.9-5.8), and 8.3 (95% CI, 5.9-11.5), respectively. Men with unweighted scores of
      1, 2, and >=3 (vs. 0) had subhazard ratios of 2.5 (95% CI, 1.8-3.5), 4.5 (95% CI,
      3.2-6.3), and 10.3 (95% CI, 7.2-14.7), respectively. The C-indexes for prediction
      of other-cause mortality were nearly identical for weighted scores (0.759 [95%
      CI, 0.715-0.780]) and unweighted scores (0.756 [95% CI, 0.717-0.780]). The
      difference in C-index between the two methods was -0.003 (95% CI, -0.01 to
      0.004). CONCLUSIONS: An unweighted Charlson score yields similar strength of
      association and variance in predicting long-term, other-cause mortality compared
      with a weighted Charlson score. PATIENT SUMMARY: A simple count of major
      comorbidities provides similar accuracy to a weighted index in predicting death
      from other causes in men with early-stage prostate cancer.

PMID- 24924555
TI  - To flee, or not to flee, that is the question for older asylum seekers.

PMID- 24924556
TI  - Candida albicans promotes invasion and colonisation of Candida glabrata in a
      reconstituted human vaginal epithelium.
AB  - OBJECTIVE: The principal aim of this study was to investigate the in vitro co
      infection of a reconstituted human vaginal epithelium (RHVE) by Candida albicans
      and Candida glabrata. METHODS: The ability of both species to invade and colonise
      the RHVE was examined using species-specific peptide nucleic acid (PNA) probe
      hybridisation, confocal laser scanning microscopy (CLSM) and a novel qRT-PCR
      protocol for Candida quantification in the tissues. RHVE damage was evaluated by
      measuring lactate dehydrogenase (LDH) activity. Candida virulence gene expression
      (HWP1, ALS, EPA, PLB, PLD and SAP) was evaluated by quantitative RT-PCR. RESULTS:
      The results showed that whilst both species induced damage to the RHVE, this was
      notably less with C. glabrata. Interestingly, there was a significant increase in
      C. glabrata RHVE colonisation and invasiveness when it was added to the tissue
      with C. albicans. The extent of RHVE damage caused by the two species appeared to
      be primarily dependent on the process of invasion. Of the virulence genes
      assayed, HWP1, PLD1 and ALS3 were deemed to be most associated with pathogenicity
      in the model. CONCLUSIONS: For the first time, we have demonstrated that the RHVE
      model coupled with specific tools of analysis, allows assessment of Candida
      colonisation and invasion in single and co-infection. Using this model we have
      demonstrated that C. albicans enhanced C. glabrata colonisation, invasion and
      tissue damage, which was also evidenced by the expression of virulence genes.

PMID- 24924557
TI  - Aspergillus in the lower respiratory tract of immunocompetent critically ill
      patients.
AB  - OBJECTIVES: To shed light on the meaning of Aspergillus-positive lower
      respiratory-tract samples in non immunocompromized critically ill patients.
      METHODS: Multicentre matched case-control (1:5) study. We used prospectively
      collected data to identify risk factors for Aspergillus-positive specimens, as
      well as outcomes in Aspergillus-positive patients. RESULTS: 66 cases (5 with
      definite invasive pulmonary aspergillosis (IPA), 18 with probable IPA, and 43
      colonisations) were matched to 330 controls. In the multivariate conditional
      logistic model, independent risk factors for at least one Aspergillus-positive
      respiratory-tract specimen were worse SAPSII at admission [OR, 1.10; 95%CI, 1.00
      1.21], ARDS [OR, 2.64; 95%CI, 1.29-5.40]; long-term steroid therapy [OR, 4.77;
      95%CI, 1.49-15.23]; steroid therapy started in the ICU [OR, 11.03; 95%CI, 4.40
      27.67]; and bacterial infection [OR, 2.73; 95%CI, 1.37-5.42]. The risk of death,
      compared to the controls, was not higher in the cases overall [HR, 0.66; 95%CI,
      0.41-1.08; p = 0.1] or in the subgroups with definite IPA [HR, 1.60; 95%CI, 0.43
      5.94; p = 0.48], probable IPA [HR, 0.84; 95%CI, 0.28-2.50; p = 0.76], or
      colonisation [HR, 0.58; 95%CI, 0.33-1.02; p = 0.06]. In cases who received
      antifungal therapy, mortality was not lower than in untreated cases [HR, 0.67;
      95%CI, 0.36-1.24; p = 0.20]. CONCLUSIONS: In critically ill immunocompetent
      patients, risk factors for presence of Aspergillus in lower respiratory tract
      specimens are steroid therapy (either chronic or initiated in the ICU), ARDS, and
      high severity of the acute illness. Prospective studies are warranted to further
      examine these risk factors and to investigate immune functions as well as the
      impact of antifungal therapy on patient outcomes.

PMID- 24924558
TI  - Lost in translation, or overestimating administrative data for outcome control in
      colorectal surgery.

PMID- 24924559
TI  - Letter from the president.

PMID- 24924565
TI  - The impact of a locally applied vibrating device on outpatient venipuncture in
      children.
AB  - OBJECTIVE: To assess the impact of a locally applied vibrating device on
      outpatient venipuncture in children. METHOD: A retrospective review of survey
      data collected prospectively as part of a quality improvement project. Both
      patients and phlebotomists were surveyed. The sample consisted of 64 children
      aged 4 to 18 years (29 prior to the implementation of the vibrating device and 35
      afterward) and 7 phlebotomists. RESULTS: Prior to the use of the vibrating
      device, 17 children (59%) indicated that they wished something had been done to
      decrease venipuncture pain. Eighty percent of the cohort that used the vibrating
      device indicated that they would like it used for future procedures. Children
      with previous venipuncture experiences appeared to benefit most from use of the
      vibrating technique. The phlebotomists reported that vibration made the procedure
      easier in 81% of the cases; none reported that it complicated the procedure.
      CONCLUSIONS: Locally applied vibration appears to be a well-accepted technique to
      minimize pediatric venipuncture discomfort that may facilitate completion of the
      procedure.

PMID- 24924564
TI  - Towards a clinically useful diagnosis for mild-to-moderate conditions of
      medically unexplained symptoms in general practice: a mixed methods study.
AB  - BACKGROUND: Symptoms that cannot be attributed to any known conventionally
      defined disease are highly prevalent in general practice. Yet, only severe cases
      are captured by the current diagnostic classifications of medically unexplained
      symptoms (MUS). This study explores the clinical usefulness of a proposed new
      diagnostic category for mild-to-moderate conditions of MUS labelled 'multiple
      symptoms'. METHODS: A mixed methods approach was used. For two weeks, 20 general
      practitioners (GPs) classified symptoms presented in consecutive consultations
      according to the International Classification of Primary Care (ICPC) supplemented
      with the new diagnostic category 'multiple symptoms'. The GPs' experiences were
      subsequently explored by focus group interviews. Interview data were analysed
      according to ethnographic principles. RESULTS: In 33% of patients, GPs classified
      symptoms as medically unexplained, but applied the category of 'multiple
      symptoms' only in 2.8%. The category was described as a useful tool for promoting
      communication and creating better awareness of patients with MUS; as such, the
      category was perceived to reduce the risk of unnecessary tests and referrals of
      these patients. Three main themes were found to affect the clinical usefulness of
      the diagnostic category of 'multiple symptoms': 1) lack of consensus on
      categorisation practices, 2) high complexity of patient cases and 3) relational
      continuity (i.e. continuity in the doctor-patient relationship over time). The
      first two were seen as barriers to usefulness, the latter as a prerequisite for
      application. The GPs' diagnostic classifications were found to be informed by the
      GPs' subjective pre-formed concepts of patients with MUS, which reflected more
      severe conditions than actually intended by the new category of 'multiple
      symptoms'. CONCLUSIONS: The study demonstrated possible clinical benefits of the
      category of 'multiple symptoms', such as GPs' increased awareness and
      informational continuity in partnership practices. The use of the category was
      challenged by the GPs' conceptual understanding of MUS and was applied only to a
      minority of patients. The study demonstrates a need for addressing these issues
      if sub-threshold categories for MUS are to be applied in routine care. The
      category of 'multiple symptoms' may profitably be used in the future as a risk
      indicator rather than a diagnostic category.

PMID- 24924566
TI  - [A retrospective cohort study regarding the effect of sirolimus-based
      immunosuppression protocol on the long-term survival of hepatocellular carcinoma
      patients after liver transplantation].
AB  - OBJECTIVE: To evaluate the influence of sirolimus on the long-term survival of
      patients after orthotopic liver transplantation (OLT) for hepatocellular
      carcinoma (HCC). METHODS: Clinic data of 165 consecutive patients who underwent
      OLT for HCC from February 2005 to March 2012 was analyzed retrospectively. Among
      them, 94 patients were treated with a sirolimus-based immunosuppressive protocol
      after OLT, while the other 71 patients with a FK506-based protocol. Postoperative
      survival time, survival, disease-free survival (DFS) and tumor recurrence rates
      between the two groups were compared. RESULTS: The 2 groups were comparable in
      all clinicopathologic parameters. The sirolimus-based group had higher patient
      survival rates than the control group at 1-year (87% vs. 97%, P = 0.03), 2-year
      (80% vs. 88%), 3-year (76% vs. 85%) and 5-year (63% vs. 75%). The 1-year, 2-year,
      3-year and 5-year recurrence rates were 12% vs. 3%, 17% vs. 9%, 21% vs. 9% (P =
      0.04) and 31% vs. 16% (P = 0.03). Early and mid-HCC (I - II stage) of 131 cases
      (control group 61 cases, sirolimus-based group of 70 patients). The 1-year, 2
      year, 3-year and 5-year survival rates were 90% vs. 97% , 80% vs. 90%, 78% vs.
      86% and 65% vs. 82% (P = 0.04) and recurrence rates were 10% vs. 3%, 16% vs. 8%,
      18% vs. 8% and 29% vs. 11% (P = 0.01). CONCLUSION: The sirolimus-based
      immunosuppressive protocol reduce long-term postoperative recurrence rate and
      improve the survival rate of patients after OLT for HCC significantly (especially
      early-mid HCC).

PMID- 24924567
TI  - [Outcome of laparoscopic radical right hemicolectomy with complete mesocolic
      resection and D3 lymphadenectomy].
AB  - OBJECTIVE: To investigate the feasibility of laparoscopic approach for totally
      mesocolic resection and D3 lymphadenectomy in right colectomy. METHODS: A
      retrospective study was conducted to analyze the operating time, blood loss,
      lymph node retrieval, postoperative complications and converting rate. The
      relationships of 3-year disease-free survival (DFS), 3-year overall survival (OS)
      to gender, age, American Society of Anesthesiologists (ASA) score, body mass
      index (BMI), T-staging, N-staging and TNM classification were also analyzed by
      Kaplan-Meier surviving curve and Log-rank test. RESULTS: A total of 111 patients
      were enrolled in present study. There were 50 male and 61 female patients. The
      average operating time was (168 +/- 42) minutes, blood loss was (81 +/- 63) ml,
      lymph node retrieval was (30 +/- 12). The converting rate to open surgery was
      1.8%. There was no death within 30 days after operation. The 3-year DFS and 3
      year OS was 86.5% and 93.7% respectively. The short-term complications occurred
      in 17.1% of the patients, including diarrhea (7 cases), ileus (3 cases), urinary
      infection (3 cases), wound dehiscence (2 cases) and so on. With the T staging
      progress, DFS and OS in patients showed a gradual decline, but the difference did
      not reach statistical significance (P > 0.05). TNM classification had relation to
      DFS (chi(2) = 6.985, P = 0.030), while N-staging showed significant relations
      both to DFS and OS (chi(2) = 14.397, P = 0.001; chi(2) = 16.699, P = 0.000).
      CONCLUSION: Laparascopic approach to right hemicolectomy with complete mesocolic
      resection and D3 lymphadenectomy is safe and has satisfied oncological outcome.

PMID- 24924568
TI  - [A single-center retrospective study on the intraluminal implantation of inferior
      vena cava filter for the lower extremity trauma patients with deep venous
      thrombosis].
AB  - OBJECTIVE: To evaluate the application of inferior vena cava filter (IVCF) in
      prevention of peri-operative pulmonary embolism (PE) in lower limb bone fracture
      patients with deep venous thrombosis (DVT). METHODS: From January 2003 to
      December 2012, 2 248 cases of lower limb and pelvic fractures with DVT were
      retrospectively analyzed. Before the procedure of IVCF implantation began,
      January 2003 to December 2007, there were 1 052 cases of acute trauma patients
      with DVT were classified as the group of early none-IVCF. The IVCF implantation
      was began since January 2008. From that time to December 2012, 712 cases of bone
      fractures with DVT received filter implantation, which were classified as IVCF
      group. The other 484 patients who had not undergone filter deployment were
      divided as group of late none-IVCF. The baseline conditions of the three groups
      were significantly different in addition to the ages between group of early none
      IVCF and IVCF group. The incidences of PE and mortality of PE in each group were
      recorded and analyzed by chi(2) test. RESULTS: There were totally 31 cases of
      symptomatic PE, among which 12 cases died. Totally 712 filters were deployed
      successfully without any major complications. The incidences of symptomatic PE
      were 0.14% (1/712), 2.19% (23/1 052) and 1.45% (7/484) in IVCF group, group of
      early none-IVCF and group of late none-IVCF, respectively. The mortality of PE
      were 0 (0/712), 0.86% (9/1 052) and 0.62% (3/484) in these groups. The incidence
      of symptomatic PE in IVCF group was significantly different from that in the
      group of early and late none-IVCF (chi(2) = 11.762, P = 0.001; chi(2) = 7.395, P
      = 0.007, respectively). The mortality of IVCF group was also significantly lower
      compared with the other two groups (chi(2) = 6.122, P = 0.013; chi(2) = 4.424, P
      = 0.035, respectively). CONCLUSION: IVCF implantation effectively prevents
      symptomatic and fatal PE of patients of lower limb and pelvic fractures with DVT
      in the peri-operative period.

PMID- 24924569
TI  - [The significance of lumbar MRI in the diagnosis of recurrented lumbar disc
      herniation after surgery].
AB  - OBJECTIVE: To retrospectively evaluate the clinical evaluation of preoperative
      lumbar T2 sagittal MRI image in predicting the recurrent lumbar disc herniation
      (RLDH). METHODS: Between January 2009 and April 2011, 28 patients were diagnosed
      as recurrent L4-5 disc herniation within 2.5 years after surgery, and 25 of them
      were included in the study as relapse group. At the same time, selected 25
      patients implemented the same surgical methods in the same level as a control
      group randomly, they were all with good to excellent result and the follow-up
      time was at least 2.5 years. There was no statistical significance between the
      two groups in gender, age and body mass index(BMI) (P > 0.05). The lumbar MRI
      image of two groups of patients before surgery were collected and analyzed, with
      the disc degeneration grade classified. The chi(2) test was used to analyzed the
      difference of degeneration between the two groups of patients before surgery.
      Rank correlation analysis evaluated the correlation between disc degeneration and
      the period of time from the first operation to the recurrence. RESULTS: In terms
      of preoperative lumbar disc degeneration, there were 22 cases of low-grade disc
      degeneration and 3 cases of advanced disc degeneration in the relapse group and 5
      cases and 20 cases respectively in the control group. there was significant
      difference between two groups (chi(2) = 23.27, P < 0.05), low-grade disc
      degeneration (gradesIand III) was significantly more frequent in the relapse
      group than in the control group. The patients with low-grade disc degeneration
      had a higher risk of recurrence, that was the risk of recurrent disc herniation
      increased by a factor of 4.4 from advanced disc degeneration to low-grade disc
      degeneration(OR = 4.4, 95%CI:1.983-9.765, P < 0.05). In cases of recurrence, the
      time interval between primary surgery and the recurrence of the patient with
      advanced disc degeneration was longer compared with low-grade disc degeneration
      (r = 0.733, P < 0.05). CONCLUSIONS: Preoperative lumbar MRI image may suggest the
      possibility of the recurrence lumbar disc herniation.Light disc degeneration is
      an important risk factor for recurrent disc herniation, and the time interval
      between primary surgery and the recurrence is positively correlated with severity
      of disc degeneration.

PMID- 24924570
TI  - [Surgical treatment of aortic paravalvular abscess by infective endocarditis].
AB  - OBJECTIVE: To summarize the clinical features, pathology and surgical treatment
      experiences in the patients with aortic paravalvular abscess by infective
      endocarditis. METHODS: The study consisted of a retrospective analysis of 29
      cases with aortic paravalvular abscess by infective endocarditis underwent
      surgical treatment between January 2001 and June 2013. Among the 29 patients, 22
      were male and 7 were female, and the mean age was (37 +/- 16) years (range from
      11 to 63 years). The primary cardiac disease was congenital aortic valve
      malformation in 16 patients. There were 15 patients with a history of severe
      heart failure. Of 29 cases, 8 abscess cavities, 13 pseudoaneurysms and 6 fistulas
      were found, and complete aortoventricular discontinuity was present in 5 patients
      with serious infections. Of them, the abscess was above the annulus in 14
      patients and below the annulus in 10 patients, and simultaneously involved the
      annulus above and below in 5 patients. 19 patients were culture positive either
      positive preoperative blood cultures or positive cultures of surgical specimens,
      including 9 patients with Staphylococcus infection. The paravalvular defect was
      repaired by patch in 19 cases, and by local closure in 10 cases. The valvular
      annulus was reconstructed simultaneously in 16 patients. Aortic valve replacement
      was performed in 26 patients, and Bentall procedure in 2 patients, including 23
      with prosthetic mechanical valve and 5 with biological valve. RESULTS: Of the
      total 29 patients, 28 patients were recovered, and 1 patient was died of sepsis.
      During 3 months to 13 years postoperative follow-up (average 4.5 years), one was
      died of non-cardiac cause, and no patient had recurrent endocarditis and
      paravalvular leakage. CONCLUSIONS: Aortic paravalvular abscess by infective
      endocarditis is not uncommon, prone to heart failure. According to the different
      pathological manifestations, the appropriate surgical approach and strategy can
      achieve satisfactory outcomes.

PMID- 24924571
TI  - [The effects of warm ischaemia time on renal function after laparoscopic partial
      nephrectomy in patients].
AB  - OBJECTIVE: To assess the effects of warm ischaemia time (WIT) on renalfunction
      after laparoscopic partial nephrectomy (LPN) for renal masses in patients.
      METHODS: From January 2010 to December 2012, 39 patients treated with LPN for a
      single T1 renal tumor were enrolled in this prospective study. There were 24 male
      and 15 female patients. Their age was (58 +/- 10) years old, and their body mass
      index was (27 +/- 3) kg/m(2). The mean operation time was (132 +/- 12) minutes,
      and the mean WIT was (29 +/- 8) minutes. Clinical parameters, the single
      glomerular filtration rates (sGFR) were compared before the operation and after 3
      and 12 months in order to observer the effects on renal function and find the
      factors predicting the renal function impairment. RESULTS: There were significant
      differences between 3, 12 months after the operation ((26.8 +/- 5.6) ml/min and
      (28.6 +/- 5.6) ml/min, respectively) and preoperation ((31.9 +/- 6.3) ml/min) in
      sGFR (F = 4.882 and 5.511, both P < 0.05). And there were significant negative
      correlations between the sGFR in 3 and 12 months after the operation and WIT (r =
      -0.569, P = 0.000 and r = -0.448, P = 0.004) . The preoperative sGFR (beta =
      0.260, 95%CI:0.089-0.431) and WIT (beta = 0.369, 95%CI:0.189-0.555) were
      independent predictors for function decline of the operated kidney (both P <
      0.05). The analysis showed that the effects of WIT within 30 minutes on renal
      function is relatively small. Longer WIT was associated with lower postoperative
      sGFR values (F = 22.128 and 20.552, both P = 0.000) . CONCLUSIONS: For the LPN
      operation, the longer of the WIT, the more serious of renal function damage. sGFR
      is an accurate measurement to assess the renal damage. Every effort should be
      made to minimise WIT during LPN, and the limit of 30 minutes should be not
      exceeded.

PMID- 24924572
TI  - [Microsurgical resection of anterior clinoid meningiomas-- 46 cases report].
AB  - OBJECTIVE: To investigate the microsurgical tchniques and effects for the
      resection of anterior clinoid meningioma (ACM). METHODS: Between January 2003 and
      March 2013, a total of 46 ACM patients were operated on via the pterion approach
      or lateral subfrontal approach. There were 16 male patients and 30 female
      patients, their mean age was 48.5 (16-69) years. Symptoms lasted from 1 month to
      9 years(average 24.7 months). Preoperative CT and MRI examination showed that the
      tumors were located in the anterior clinoid process (25 cases on the right side,
      21 cases on the left side). The average maximal tumor diameter was 4.4 cm (1.9
      7.4 cm). The patients were peroidly followed-up on outpatient on 3 months to 6
      months, then every year postoperativelly. The clinical data, radiological
      findings, surgical records and outcome of patients were retrospectively analyzed,
      and the prognostic factors were ananlyzed by using of the unpaired data chi(2)
      test with continuity correction. RESULTS: Of fourty-six patients operated on,
      apparently complete removal was achieved in 36 patients (78.3%), 10 patients
      (21.7%) had minimal residual tumors, 5 of which had gamma knife radiosurgery.
      Preexisting visual deficit improved in 21 of 41 patients (51.2%), unchanged in
      16(35.6%), and worsened in 9(20.0%). At 3-6 months after discharge, 37(80.4%)
      patients had a good recovery, 7(15.6%) patients were moderately disabled, 1(2.2%)
      presented with severe disability, and 1 (2.2%) patient died of surgery-related
      causes. The tumor wrapping blood vessels (chi(2) = 4.676, P = 0.031) and
      violating cavernous sinus(chi(2) = 4.973, P = 0.026) were causes of unfavorable
      prognosis. During the mean follow-up of 35.1 months (range, 4-107 months) for 40
      patients, the average Karnofsky score was 83.2. Tumor recurred in 4 cases: 2 of
      which required reoperation, and 2 had gamma knife radiosurgery. CONCLUSIONS:
      Tumor wrapped vessels and invasion of the cavernous sinus are important
      unfavorable prognostic factors for ACM resection. By using appropriate surgical
      strategies and techniques, ACM can be removed safely via the pterion approach or
      lateral subfrontal approach with relatively low morbidity and mortality.

PMID- 24924573
TI  - [The surgery of giant symptomatic cavernous sinus aneurysms].
AB  - OBJECTIVE: To evaluate the management and outcomes in patients with giant
      symptomatic cavernous sinus aneurysms who underwent aneurysms trapping with
      bypass, proximal carotid occlusion and aneurysms trapping. METHODS: Twenty-three
      patients with giant symptomatic cavernous sinus aneurysms underwent surgery
      between February 2007 and March 2013, 3 cases were male and 20 cases were female
      patients, the age of the patients ranged between 24 and 68 years, mean age was
      54.7 years. The pre-operative digital subtraction angiography (DSA) and ballon
      occlusion test (BOT) were performed to confirm the diagnosis and identify
      hemodynamic reserve with carotid occlusion, and the aneurysms trapping with
      bypass, aneurysms trapping and proximal occlusion of the internal carotid artery
      were performed according to BOT results. During the surgery, the
      neurophysiological monitoring and the intraoperative CT perfusion were used. The
      follow-up by DSA or CT angiography were made. RESULTS: Seventeen patients
      underwent aneurysms trapping with bypass, 1 underwent aneurysms trapping and 5
      underwent proximal occlusion of the internal carotid artery. After surgery,
      symptom improved in 4 cases, did not change in 10 cases, and new neural function
      deficit developed in 9 cases. The follow-up period were 3 months to 75 months.
      Two patients were lost. The Glasgow Outcome Scale of last follow-up were 5 in 19
      patients, 3 in 1 patient and 1 in 1 patient. CONCLUSIONS: The aneurysms trapping
      with bypass and proximal occlusion of the internal carotid artery are effective
      and reliable procedure for treatment of giant symptomatic cavernous sinus
      aneurysms in selected patients after evaluation of the pre-operative BOT, intra
      operative neurophysiological monitoring and the intraoperative CT perfusion.

PMID- 24924574
TI  - [Automated proton magnetic resonance spectroscopy imaging guided frameless
      stereotactic biopsy of intracranial lesions].
AB  - OBJECTIVE: To evaluate the feasibility, reliability and accuracy of the automated
      magnetic resonance spectroscopy ((1)H-MRS) guided frameless brain biopsy with
      intraoperative magnetic resonance imaging (iMRI). METHODS: Between July 2011 and
      July 2013, a consecutive series of 93 patients were prospectively enrolled. All
      the patients had intracranial lesions which need biopsy to confirm the diagnosis.
      Among them, 48 patients were male, 45 patients were female. Their age range from
      7 years to 76 years, the median age was 47 years. All patients underwent MRS
      examination. With MRS automatic fusion technique, the metabolic images were
      integrated into a standard navigation system (Vario Guide) to guide frameless
      biopsy. High-field iMRI (1.5 T) was used for target inspection, brain shift
      correction, and intra-operative exclusion of intra-cerebral hemorrhage and other
      complications. RESULTS: For all the 93 patients, (1)H-MRS based metabolic images
      could be automatically integrated into a standard navigation system and average
      fusion procedure could be taken 5 minutes 6 seconds. For (1)H-MRS guided
      stereotactic biopsy of intracranial lesions, the diagnosis yield rate was 94.6%
      (88/93). Four cases did not get a clear pathological diagnosis, while 1 case did
      not match the pathological diagnosis result which obtained by following
      craniotomy. Technical related complication rate was 2.2% (2 cases, intra-cerebral
      hemorrhage), which were intra-operatively depicted with iMRI, and managed
      properly. Among them, 1 case with small volume (5 ml) intracerebral hematoma
      fully recovered 10 days after surgery without second surgical intervention. One
      case with large volume intracerebral hematoma (32 ml) was depicted with iMRI,
      followed by craniotomy and hematoma evacuation in the same session. This case had
      no new or worsened neurologic deficit post-operatively. CONCLUSIONS: (1)H-MRS
      based metabolic imaging can be automatically integrated into a standard
      navigation system and used for frameless brain biopsy. The target can be selected
      according to the metabolic status of the lesion. Hence, the target can be more
      accurate. And the pathological diagnosis yield rate is higher. With iMRI, the
      method is safe, and has high clinical efficacy.

PMID- 24924575
TI  - [A retrospective analysis of 5 cases of major burns treated by goat acellular
      dermal matrix combined with hyaluronic acid].
AB  - OBJECTIVE: To evaluate the clinical efficacy of the goat acellular dermal matrix
      combined with hyaluronic acid (h-GADM) in the treatment of major burns. METHODS:
      A retrospective analysis of 5 patients with major burns undergoing combines
      microskin and h-GADM grafting. All patients were male, aged 33 to 50 years, and
      mean burn area were 83% +/- 11%, which III degree wounds 60% to 90%. After
      extensive burns patients admitted to hospital in accordance with conventional
      treatment processes included fluid resuscitation, airway management, wound
      management, infection control and other treatment. The patients received the
      surgery after the shock of spending and hemodynamically stable. Summarized the
      feasibility and operative techniques of the new method, and elaborated on details
      by a typical case as an example. RESULTS: All the 5 patients were survival, go
      through the shock period smoothly, not haven any serious complications as lung
      infection, wound sepsis, septicemia and kidney failure occurred. A total of nine
      mircoskin graft operations were undergoing and covered 17 limbs. The average time
      of the h-GADM desquamtion was (17.7 +/- 2.7) days after operation, the
      hospitalization time was (115 +/- 27) days. After (72 +/- 6) days, the residual
      wound was less than 5% total body surface area. CONCLUSION: The h-GAMD can be a
      good alternative to cadaver skin in the treatment of major burns.

PMID- 24924576
TI  - [Detection of bladder cancer by narrow band imaging cystoscopy: a meta-analysis].
AB  - OBJECTIVES: To evaluate the value of narrow band imaging (NBI) cystoscopy in
      detection of bladder cancer. METHODS: Literatures on narrow-band imaging
      cystoscopy in diagnosis of bladder cancer, controlled clinical research was
      searched in PubMed, Cochrane Library,EMbase, and the Chinese Biomedical
      Literature Database. The literatures were selected according to the inclusion and
      exclusion criteria. The Meta-DiSc 1.4 software was used to review management and
      analysis. RESULTS: The 8 studies met the inclusion criteria. On a per-people
      analysis, the pooled sensitivity, specificity, positive likelihood ratio,
      negative likelihood ratio, diagnostic odds ratio (DOR) of NBI cystoscopy and
      white light imaging (WLI) cystoscopy were respectively 0.943 (95%CI: 0.914-0.964)
      and 0.848 (95%CI: 0.803- 0.885), 0.847 (95%CI: 0.812-0.878) and 0.870 (95%CI:
      0.831-0.903), 7.038 (95%CI: 3.357-14.754) and 6.938 (95%CI: 2.052-23.465), 0.054
      (95%CI: 0.012-0.237) and 0.181 (95%CI: 0.091-0.361), 185.32 (95%CI: 45.714
      751.260) and 42.931 (95%CI: 8.088-227.880). The areas under the curve (AUC) and
      Q* of NBI cystoscopy and WLI cystoscopy were 0.978 and 0.894, 0.934 and 0.825
      respectively. CONCLUSION: NBI cystoscopy is accurate with high diagnostic
      precision for diagnosis of bladder cancer. NBI cystoscopy is prior to WLI
      cystoscopy, but it needs more clinical evidence for further affirmance.

PMID- 24924577
TI  - [Comparing different treatments for femoral neck fracture of displacement type in
      the elderly:a meta analysis].
AB  - OBJECTIVE: To compare the effects and security between internal fixation and
      total hip arthroplasty for the patients in elderly with femoral neck fracture of
      displacement type through a meta analysis. METHODS: Studies on comparison between
      internal fixation and total hip arthroplasty for the patients in the elderly with
      femoral neck fracture of displacement type were identified from PubMed
      database,EMBase database, COCHRANE library, CMB database, CNKI database and
      MEDLINE database. Data analysis were performed using Revman 5.2.6(the Cochrane
      Collaboration). RESULTS: Six published randomized controlled trials including 627
      patients were suitable for the review, 286 cases in internal fixation group and
      341 cases in total hip arthroplasty group. The results of meta analysis indicated
      that statistically significant difference were observed between the two groups in
      the quality of life which was reflected by the Harris scale (RR = 0.82,
      95%CI:0.72-0.93, P < 0.05) , the reoperation rate (RR = 5.81, 95%CI:3.09-10.95, P
      < 0.05) and the major complications rate (RR = 3.60, 95%CI:2.29-5.67, P < 0.05)
      postoperatively. There were no difference in the mortality at 1 year and 5 years
      postoperatively(P > 0.05). CONCLUSIONS: For the patients with femoral neck
      fracture of displacement type in the elderly, there is no statistical difference
      between two groups in the mortality postoperatively. The quality of life and the
      security of operation in internal fixation group is worse than the total hip
      arthroplasty group.

PMID- 24924578
TI  - Diet-induced and age-related changes in the quadriceps muscle: MRI and MRS in a
      rat model of sarcopenia.
AB  - BACKGROUND: Knowledge about the molecular pathomechanisms of sarcopenia is still
      sparse, especially with regard to nutritional risk factors and the subtype of
      sarcopenic obesity. OBJECTIVE: The aim of this study was to characterize diet
      induced and age-related changes on the quality and quantity of the quadriceps
      muscle in a rat model of sarcopenia by different magnetic resonance (MR)
      techniques. METHODS: A total of 36 6-month-old male Sprague-Dawley rats were
      randomly subdivided into 2 groups and received either a high-fat diet (HFD) or a
      control diet (CD). At the age of 16 months, 15 HFD and 18 CD rats underwent MR at
      1.5 T. T1-weighted images as well as T2 relaxation time maps were acquired
      perpendicular to the long axis of the quadriceps muscles. Maximum cross-sectional
      area (CSA) of the quadriceps muscle was measured on T1-weighted images, and T2
      relaxation times of muscle were assessed in a region without visible
      intramuscular fat (T2lean muscle) and across the complete CSA (T2muscle).
      Furthermore, (1)H-MR spectroscopy was performed to evaluate the relative lipid
      content of the quadriceps muscles. These measurements were repeated 5 months
      later in the surviving 8 HFD and 14 CD rats. RESULTS: HFD rats revealed
      significantly decreased CSA and CSA per body weight (BW) as well as prolonged T2
      relaxation times of muscle. A higher weight gain (upper tertile during the first
      6 months of diet in CD rats) resulted in a significant change of T2muscle, but
      had no relevant impact on CSA. Advancing age up to 21 months led to significantly
      decreased BW, CSA and CSA/BW, significantly prolonged T2muscle and T2lean muscle
      and enlarged lipid content in the quadriceps muscle. CONCLUSIONS: In an
      experimental setting a chronically fat-enriched diet was shown to have a relevant
      and age-associated influence on both muscle quantity and quality. By
      translational means the employed MR techniques give rise to the possibility of an
      early detection and noninvasive quantification of sarcopenia in humans, which is
      highly relevant for the field of geriatrics.

PMID- 24924579
TI  - Apps for management of sick newborn: evaluation of impact on health care
      professionals.
AB  - The objective of the study was to evaluate the efficacy of interactive mobile
      device application 'Apps on sick newborn care' as a training tool, in improving
      the knowledge and skill scores of postgraduate nursing students (N = 27). A
      training workshop was conducted in small workstations by the facilitators using
      the modules on android device and preloaded videos in which the procedure was
      systematically demonstrated. A mixed-methods approach consisting of pre-post
      tests, Likert's scale and focus group discussion were used to assess the
      knowledge, skills and perception of the participants. The scores in multiple
      choice questions (pre and post, 12.4 +/- 2.2 and 19.7 +/- 3.6; P < 0.001) and
      composite Objective Structured Clinical Examination scores (32.8 +/- 7.3 vs. 63.7
      +/- 7.1; P < 0.001) significantly improved after training. The students derived
      overall satisfaction from the training using the device. Such applications have
      potential to train health-care professionals. 

PMID- 24924581
TI  - Reply to the correspondence on "Possible spontaneous PFO closure after thrombus
      trapped in PFO", Antonia Schulz et al., Clin Res Cardiol 2014; 103:333-335.

PMID- 24924580
TI  - Impact of the learning curve on outcome after transcatheter mitral valve repair:
      results from the German Mitral Valve Registry.
AB  - AIMS: This analysis from the German Mitral Valve Registry investigates the impact
      of the learning curve with the MitraClip((r)) technique on procedural success and
      complications. METHODS AND RESULTS: Consecutive patients treated since 2009 in
      centers that performed more than 50 transcatheter mitral repairs were included.
      Results of the first half of the patients were compared to those of the second.
      Altogether 496 patients from 10 centers were included. Patients treated later had
      less common severe heart failure symptoms (patients with NYHA IV: 22.1 vs. 14.5
      %, p < 0.05). The EuroSCORE I (22.0 vs. 23.0 %, p = ns) and Society of Thoracic
      Surgeons (STS) score (7.5 vs. 9.5 %, p = ns) did not differ between both groups.
      Procedural success was 95.6 % (238/249) in the first cases and 94.7 % (232/245, p
      = ns) subsequently. Also procedural time (104.3 vs. 119 min, p = ns) and
      complications did not decrease over time. CONCLUSION: A learning curve using the
      MitraClip((r)) device does not appear to significantly affect acute MR reduction,
      hospital and 30-day mortality. Most likely, the proctor system leads to already
      high initial procedure success and relatively short procedure time.

PMID- 24924582
TI  - Detection of common and less frequent EGFR mutations in cytological samples of
      lung cancer.
AB  - OBJECTIVE: Lung cancer represents the leading cause of cancer death. EGFR
      mutations, detected in 10-40% of lung adenocarcinomas, are an essential key to
      therapeutic management. EGFR-activated mutations comprise mainly deletions in
      exon 19 and point mutations in exon 21. Although histology is the traditional
      method of detection, we investigated the role of cytology in EGFR mutations.
      STUDY DESIGN: A total of 774 lung cancers were studied for EGFR mutations (676
      histological and 98 cytological samples), including 424 adenocarcinomas, 326 non
      small cell lung carcinomas not otherwise specified, and 24 squamous cell
      carcinomas. RESULTS: We had a total of 164 (21.2%) cases of mutations. Common
      mutations were short in-frame deletions in exon 19 (53.7%) and single-nucleotide
      substitutions in exon 21 (34.1%); less frequent mutations included single
      nucleotide substitutions in exon 18 (3.7%) and in-frame insertions/deletions in
      exon 20 (8.5%). Histologically, EGFR mutations in exons 19 and 21 occurred in
      19.4% and in exons 18 and 20 in 2.2%, while the rates cytologically were 13.3%
      for exons 19 and 21 and 5.1% for exons 18 and 20. CONCLUSIONS: The sensitivity
      for the detection of EGFR mutations in cytological samples overlaps histology, so
      the use of cytological material constitutes an adequate approach for treatment
      selection in patients with locally advanced or metastatic lung cancer.

PMID- 24924583
TI  - Defining the autonomy gap: when expectations do not meet reality in the operating
      room.
AB  - OBJECTIVE: To develop operative independence with essential procedures by the end
      of their training, residents need graded autonomy as they progress through
      training. This study compares autonomy expectations, as defined by faculty and
      residents, with autonomy measured in the operating room. METHODS: Operative
      procedures performed by general surgery residents between November 2012 and June
      2013 were each assigned an autonomy score by the operating attending physician
      using a previously described rating scale (Zwisch). Scores range from minimum
      autonomy, "show and tell," to maximum autonomy, "supervision only." Autonomy
      expectations were defined by a survey asking faculty and residents what autonomy
      level residents should achieve during each year of training for each of the 10
      most commonly performed procedures. Faculty expectations, resident expectations,
      and actual operating room autonomy data were compared using analysis of variance
      with post hoc analysis by Tukey honestly significant difference test. RESULTS: A
      total of 1467 operative cases were scored using the Zwisch scale over the period
      of the study. The 10 most common procedures accounted for 56.3% (827) of the
      cases. Resident and faculty expectations of resident operative autonomy were
      similar. For only laparoscopic cholecystectomy, residents expected significantly
      more autonomy than the faculty did during the junior years but they agreed with
      the faculty for the chief year. When expectations were compared with actual
      performance, the resident autonomy level achieved was significantly less than
      that expected by residents or faculty or both for all 10 procedures in at least
      one postgraduate level. For every procedure performed more than 5 times during
      the study period by postgraduate years 3 to 5 residents, autonomy was
      significantly less than expected. CONCLUSIONS: Surgical faculty and residents had
      similar expectations for resident operative autonomy, yet actual resident
      performance failed to achieve those shared expectations for even the most common
      procedures. This autonomy gap provides more evidence for concerns about the
      preparedness of graduating residents for independent practice.

PMID- 24924584
TI  - External validation and evaluation of an intermediate proficiency-based knot
      tying and suturing curriculum.
AB  - PURPOSE: The purpose of this study was to perform external validation, examine
      educational effectiveness, and confirm construct validity of a previously
      developed "intermediate-level, proficiency-based knot-tying and suturing
      curriculum" in preparing residents to achieve proficiency in more advanced open
      surgical techniques. METHODS: A total of 47 postgraduate year-1 (PGY-1) surgery
      residents completed 6 intermediate-level knot-tying and suturing exercises.
      Baseline trainee performance was compared with intermediate and senior (PGY-3 and
      PGY-4) residents (n = 12) and expert faculty (n = 4). RESULTS: PGY-1 overall
      proficiency increased from 21.1% at baseline to 92.1% during posttest for all 6
      exercises combined (p < 0.001). When compared with the PGY-3 and PGY-4 residents,
      at baseline intermediate and senior residents scored higher on half of the
      exercises. However, during posttesting PGY-1 residents not only matched, but also
      surpassed PGY-3 and PGY-4 residents' performance in 3 of 6 exercises. Significant
      differences on all 6 exercises were also found during pretesting when comparing
      interns against faculty, demonstrating construct validity. However, upon
      completion of the curriculum, PGY-1 residents' posttest scores were equivalent,
      if not significantly better than expert faculty performance. CONCLUSION: We
      obtained similar results as those previously reported, showing external
      validation. Additionally, we demonstrated that first-year surgical residents
      could achieve performance levels that match or exceed those of senior residents
      and experienced surgeons on these exercises with 4 weeks of training.

PMID- 24924585
TI  - Truncating mutations in LRP4 lead to a prenatal lethal form of Cenani-Lenz
      syndrome.
AB  - Cenani-Lenz syndrome (CLS) is an autosomal recessive skeletal dysplasia that
      results in malformations of the distal limb, renal anomalies, and characteristic
      facies. In 2010, this condition was found to be caused by mutations in LRP4, a
      member of the low-density lipoprotein family of receptors. LRP4 has been shown to
      antagonize LRP5/LRP6 activation of WNT and beta-catenin signaling. Loss of LRP4
      function leads to excessive Wnt and beta-catenin signaling in the limb bud, which
      causes abnormal limb development. The large majority of patients with CLS
      reported in the literature have splicing and missense mutations, which result in
      syndactyly, oligodactyly, and minor renal malformations. More recently, a patient
      with CLS has been identified with a homozygous nonsense mutation and a more
      severe presentation of findings typically associated with this condition. Here we
      present two sibling fetuses with a prenatal lethal presentation of mesomelic limb
      reductions, oligosyndactyly, genitourinary malformation and compound
      heterozygosity for two novel truncating mutations in LRP4. These findings lend
      further support to the CLS genotype-phenotype correlation presented in recent
      publications.

PMID- 24924586
TI  - Efficacy of mechanical debridement with adjunct antimicrobial photodynamic
      therapy for the management of peri-implant diseases: a systematic review.
AB  - The aim was to assess whether or not mechanical debridement with adjunct
      antimicrobial photodynamic therapy (aPDT) is effective for the management of peri
      implant diseases. The addressed focused question was "Is mechanical debridement
      with adjunct aPDT more effective in treating peri-implant diseases as compared to
      when mechanical debridement is used alone?" PubMed/MEDLINE and Google-Scholar
      databases were searched from 1994 till April 2014 using different combinations of
      the following keywords: antimicrobial photodynamic therapy; bone loss; light
      activated disinfection; mechanical debridement; and peri-implant diseases. Review
      articles, case-reports, commentaries, letters to the editor, unpublished articles
      and articles published in languages other than English were excluded. Twelve
      studies (six clinical and six experimental) were included. In the clinical and
      experimental studies, 15-80 implants and 18-150 implants respectively were used.
      Laser wavelengths, duration of irradiation and power output ranged between 625 nm
      830 nm, 10 s-300 s, and 30 mW-200 mW, respectively. Four studies reported
      mechanical debridement with adjunct aPDT to be effective in the treatment of peri
      implant diseases; however, the benefits of aPDT were comparable with conventional
      treatments. Two studies reported aPDT to reduce bacteria more than when the laser
      and the photosensitizer were applied alone. In two studies, chemical disinfection
      and aPDT showed comparable outcomes in terms of bacterial disinfection. In two
      experimental studies, aPDT was shown to improve bone to implant contact and re
      osseointegration. Efficacy of mechanical debridement with adjunct aPDT for the
      management of peri-implant diseases remains debatable. 

PMID- 24924587
TI  - Digoxin in patients with permanent atrial fibrillation: data from the RACE II
      study.
AB  - BACKGROUND: The Atrial Fibrillation Follow-up Investigation of Rhythm Management
      trial showed that digoxin was associated with increased mortality in patients
      with atrial fibrillation. OBJECTIVES: To assess the association of digoxin with
      cardiovascular (CV) morbidity and mortality in patients with permanent atrial
      fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A
      Comparison Between Lenient Versus Strict Rate Control II trial as well as to
      assess the role of digoxin to achieve heart rate targets. METHODS: The primary
      outcome was a composite of CV morbidity and mortality. Secondary outcomes
      included CV hospitalization and all-cause mortality or heart failure (HF)
      hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment
      phase. Outcome events were analyzed from the end of the dose-adjustment phase
      until the end of follow-up. The median follow-up period was 2.9 years
      (interquartile range 2.7-3.0 years). RESULTS: In total, 284 patients (46.7%) used
      digoxin after the dose-adjustment phase (median dosage 0.250 mg; interquartile
      range 0.0625-0.750 mg). These patients were more often women, previously admitted
      for HF, had an increased left ventricular end-systolic diameter, and more often
      randomized to strict rate control. By using Cox proportional hazards regression
      analysis, the use of digoxin was not associated with an increased risk for the
      primary and secondary outcomes. For the primary outcome, the 3-year estimated
      cumulative incidence was 12.9% vs 13.4% in the digoxin group vs the no-digoxin
      group (unadjusted hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.62
      1.52). Incidence was 19.4% vs. 19.5% for CV hospitalization (unadjusted HR 1.00;
      95% CI 0.69-1.45) and 6.6% vs. 9.9% for all-cause mortality or HF hospitalization
      (unadjusted HR 0.62; 95% CI 0.34-1.13) in the digoxin group vs the no-digoxin
      group. CONCLUSION: The use of digoxin was not associated with increased morbidity
      and mortality.

PMID- 24924588
TI  - Live pups from evaporatively dried mouse sperm stored at ambient temperature for
      up to 2 years.
AB  - The purpose of this study is to develop a mouse sperm preservation method based
      on evaporative drying. Mouse sperm were evaporatively dried and stored at 4
      degrees C and ambient temperature for 3 months to 2 years. Upon rehydration, a
      single sperm was injected into a mature oocyte to develop into a blastocyst after
      culture or a live birth after embryo transfer to a recipient female. For the
      samples stored at 4 degrees C for 3, 6, 12, 18, and 24 months, the blastocyst
      formation rate was 61.5%, 49.1%, 31.5%, 32.2%, and 41.4%, respectively. The
      blastocyst rate for those stored at ambient temperature (~22 degrees C) for 3, 6,
      12, and 18 months was 57.8%, 36.2%, 33.6%, and 34.4%, respectively. Fifteen,
      eight and three live pups were produced from sperm stored at room temperature for
      12, 18, and 24 months, respectively. This is the first report of live offspring
      produced from dried mouse sperm stored at ambient temperature for up to 2 years.
      Based on these results, we suggest that evaporative drying is a potentially
      useful method for the routine preservation of mouse sperm. 

PMID- 24924589
TI  - Control of NF-kB activity in human melanoma by bromodomain and extra-terminal
      protein inhibitor I-BET151.
AB  - The transcription factor NF-kappaB (NF-kB) is a key regulator of cytokine and
      chemokine production in melanoma and is responsible for symptoms such as
      anorexia, fatigue, and weight loss. In addition, NF-kB is believed to contribute
      to progression of the disease by upregulation of cell cycle and anti-apoptotic
      genes and to contribute to resistance against targeted therapies and
      immunotherapy. In this study, we have examined the ability of the bromodomain and
      extra-terminal (BET) protein inhibitor I-BET151 to inhibit NF-kB in melanoma
      cells. We show that I-BET151 is a potent, selective inhibitor of a number of NF
      kB target genes involved in induction of inflammation and cell cycle regulation
      and downregulates production of cytokines such as IL-6 and IL-8. SiRNA studies
      indicate that BRD2 is the main BET protein involved in regulation of NF-kB and
      that I-BET151 caused transcriptional downregulation of the NF-kB subunit
      p105/p50. These results suggest that BET inhibitors may have an important role in
      treatment of melanoma where activation of NF-kB may have a key pathogenic role. 

PMID- 24924590
TI  - Quantifying the response of free-ranging mammalian herbivores to the interplay
      between plant defense and nutrient concentrations.
AB  - While trying to achieve their nutritional requirements, foraging herbivores face
      the costs of plant defenses, such as toxins. Teasing apart the costs and benefits
      of various chemical constituents in plants is difficult because their chemical
      defenses and nutrient concentrations often co-vary. We used an approach derived
      from predator-prey studies to quantitatively compare the foraging response of a
      free-ranging mammalian herbivore, the swamp wallaby (Wallabia bicolor), through
      three feeding trials with artificial diets that differed in their concentrations
      of (1) the terpene 1,8-cineole, (2) primary constituents (including nitrogen and
      fiber), and (3) both the terpene and the primary constituents. Applying the
      giving-up density (GUD) framework, we demonstrated that the foraging cost of food
      patches increases with higher dietary cineole concentration and decreases with
      higher dietary nutrient concentration. The effect of combined differences in
      nutrients and cineole concentrations on GUD was interactive, and high nutrient
      food required more cineole to achieve the same patch value as low nutrient food.
      Our results indicate that swamp wallabies equate low nutrient, poorly defended
      food with high nutrient, highly defended food, providing two contrasting diets
      with similar cost-benefit outcomes. This behavior suggests that equal
      concentrations of chemical defenses provide nutrient-poor plants with relatively
      greater protection as nutrient-rich plants. Nutrient-rich plants may therefore
      face the exacerbated problem of being preferred by herbivores and therefore need
      to produce more defense compounds to achieve the same level of defense as
      nutrient-poor plants. Our findings help explain the difference in anti-herbivore
      strategy of nutrient-poor and rich plants, i.e., tolerance versus defense. 

PMID- 24924591
TI  - Evolutionary responses of tree phenology to the combined effects of assortative
      mating, gene flow and divergent selection.
AB  - The timing of bud burst (TBB) in temperate trees is a key adaptive trait, the
      expression of which is triggered by temperature gradients across the landscape.
      TBB is strongly correlated with flowering time and is therefore probably mediated
      by assortative mating. We derived theoretical predictions and realized numerical
      simulations of evolutionary changes in TBB in response to divergent selection and
      gene flow in a metapopulation. We showed that the combination of the
      environmental gradient of TBB and assortative mating creates contrasting genetic
      clines, depending on the direction of divergent selection. If divergent selection
      acts in the same direction as the environmental gradient (cogradient settings),
      genetic clines are established and inflated by assortative mating. Conversely,
      under divergent selection of the same strength but acting in the opposite
      direction (countergradient selection), genetic clines are slightly constrained.
      We explored the consequences of these dynamics for population maladaptation, by
      monitoring pollen swamping. Depending on the direction of divergent selection
      with respect to the environmental gradient, pollen filtering owing to assortative
      mating either facilitates or impedes adaptation in peripheral populations.

PMID- 24924592
TI  - Cascade nitration/cyclization of 1,7-enynes with tBuONO and H2O: one-pot self
      assembly of pyrrolo[4,3,2-de]quinolinones.
AB  - Here we describe the one-pot construction of the pyrrolo[4,3,2-de]quinolinone
      scaffold by a cascade nitration/cyclization sequence of 1,7-enynes with tBuONO
      and H2O. The cascade proceeds through alkene nitration, 1,7-enyne 6-exo-trig
      cyclization, C-H nitrations, and redox cyclization, and exhibits excellent
      functional group tolerance. The mechanism was investigated using in situ high
      resolution mass spectrometry (HR-MS).

PMID- 24924593
TI  - Liver sinusoidal endothelial cell-mediated CD8 T cell priming depends on co
      inhibitory signal integration over time.
AB  - The initiation of adaptive immunity requires cell-to-cell contact between T cells
      and antigen-presenting cells. Together with immediate TCR signal transduction,
      the formation of an immune synapse (IS) is one of the earliest events detected
      during T cell activation. Here, we show that interaction of liver sinusoidal
      endothelial cells (LSEC) with naive CD8 T cells, which induces CD8 T cells
      without immediate effector function, is characterized by a multi-focal type IS.
      The co-inhibitory molecule B7H1, which is pivotal for the development of non
      responsive LSEC-primed T cells, did not alter IS structure or TCRbeta/CD11a
      cluster size or density, indicating that IS form does not determine the outcome
      of LSEC-mediated T cell activation. Instead, PD-1 signaling during CD8 T cell
      priming by LSEC repressed IL-2 production as well as sustained CD25 expression.
      When acting during the first 24 h of LSEC/CD8 T cell interaction, CD28 co
      stimulation inhibited the induction of non-responsive LSEC-primed T cells.
      However, after more than 36 h of PD-1 signaling, CD28 co-stimulation failed to
      rescue effector function in LSEC-primed T cells. Together, these data show that
      during LSEC-mediated T cell priming, integration of co-inhibitory PD-1 signaling
      over time turns on a program for CD8 T cell development, that cannot be
      overturned by co-stimulatory signals. 

PMID- 24924594
TI  - Longitudinal anatomical and metabolic MRI characterization of orthotopic
      xenograft prostate tumors in nude mice.
AB  - PURPOSE: To assess anatomic and functional magnetic resonance imaging (MRI) for
      monitoring of tumor volume and metabolism of orthotopic xenograft prostate cancer
      tumors. MATERIALS AND METHODS: Human-derived PC-3M cells were implanted into the
      prostate in 22 nude mice. Tumor volume and MRI appearance were monitored for up
      to 29 days. Histology was performed to detect metastases. Hyperpolarized [1-(13)
      C]pyruvate MRI was used to measure tumor metabolism on day 22. RESULTS: Tumors
      were visible by MRI 9 days after tumor cell implantation. Tumor volume increased
      to 720 +/- 190 mm(3) on day 29 of imaging. Metastasis was seen in the iliac lymph
      nodes at all timepoints, and in more distant lymph nodes at later timepoints, but
      was not detectable by MRI. Regions with low pyruvate uptake corresponded to
      regions with necrosis and had a higher lactate/pyruvate ratio (0.98 +/- 0.4 vs.
      1.6 +/- 1.1). CONCLUSION: MRI using the balanced steady-state free precession
      (bSSFP) sequence can be used to monitor tumor growth in orthotopic PC-3M tumors
      as early as 9 days post-injection. Hyperpolarized pyruvate MRI has potential to
      assess tumor metabolism and necrosis.

PMID- 24924595
TI  - Crossed SMPS MOSFET-based protection circuit for high frequency ultrasound
      transceivers and transducers.
AB  - BACKGROUND: The ultrasonic transducer is one of the core components of ultrasound
      systems, and the transducer's sensitivity is significantly related the loss of
      electronic components such as the transmitter, receiver, and protection circuit.
      In an ultrasonic device, protection circuits are commonly used to isolate the
      electrical noise between an ultrasound transmitter and transducer and to minimize
      unwanted discharged pulses in order to protect the ultrasound receiver. However,
      the performance of the protection circuit and transceiver obviously degrade as
      the operating frequency or voltage increases. We therefore developed a crossed
      SMPS (Switching Mode Power Supply) MOSFET-based protection circuit in order to
      maximize the sensitivity of high frequency transducers in ultrasound systems.The
      high frequency pulse signals need to trigger the transducer, and high frequency
      pulse signals must be received by the transducer. We therefore selected the SMPS
      MOSFET, which is the main component of the protection circuit, to minimize the
      loss in high frequency operation. The crossed configuration of the protection
      circuit can drive balanced bipolar high voltage signals from the pulser and
      transfer the balanced low voltage echo signals from the transducer. METHODS: The
      equivalent circuit models of the SMPS MOSFET-based protection circuit are shown
      in order to select the proper device components. The schematic diagram and
      operation mechanism of the protection circuit is provided to show how the
      protection circuit is constructed. The P-Spice circuit simulation was also
      performed in order to estimate the performance of the crossed MOSFET-based
      protection circuit. RESULTS: We compared the performance of our crossed SMPS
      MOSFET-based protection circuit with a commercial diode-based protection circuit.
      At 60 MHz, our expander and limiter circuits have lower insertion loss than the
      commercial diode-based circuits. The pulse-echo test is typical method to
      evaluate the sensitivity of ultrasonic transducers. Therefore, we performed a
      pulse-echo test using a single element transducer in order to utilize the crossed
      SMPS MOSFET-based protection circuit in an ultrasound system. CONCLUSIONS: The
      SMPS-based protection circuit could be a viable alternative that provides better
      sensitivity, especially for high frequency ultrasound applications.

PMID- 24924596
TI  - Managing haemophilia for life: 4th Haemophilia Global Summit.
AB  - The 4th Haemophilia Global Summit was held in Potsdam, Germany, in September 2013
      and brought together an international faculty of haemophilia experts and
      delegates from multidisciplinary backgrounds. The programme was designed by an
      independent Scientific Steering Committee of haemophilia experts and explored
      global perspectives in haemophilia care, discussing practical approaches to the
      optimal management of haemophilia now and in the future. The topics outlined in
      this supplement were selected by the Scientific Steering Committee for their
      relevance and potential to influence haemophilia care globally. In this
      supplement from the meeting, Jan Astermark reviews current understanding of risk
      factors for the development of inhibitory antibodies and discusses whether this
      risk can be modulated and minimized. Factors key to the improvement of joint
      health in people with haemophilia are explored, with Carlo Martinoli and Victor
      Jimenez-Yuste discussing the utility of ultrasound for the early detection of
      haemophilic arthropathy. Other aspects of care necessary for the prevention and
      management of joint disease in people with haemophilia are outlined by Thomas
      Hilberg and Sebastian Lobet, who highlight the therapeutic benefits of
      physiotherapy and sports therapy. Riitta Lassila and Carlo-Federico Perno
      describe current knowledge surrounding the risk of transmission of infectious
      agents via clotting factor concentrates. Finally, different types of extended
      half-life technology are evaluated by Mike Laffan, with a focus on the
      practicalities and challenges associated with these products. 

PMID- 24924598
TI  - Social determinants and lifestyle risk factors only partially explain the higher
      prevalence of food insecurity among Aboriginal and Torres Strait Islanders in the
      Australian state of Victoria: a cross-sectional study.
AB  - BACKGROUND: The prevalence of food insecurity is substantially higher among
      Australians of Aboriginal or Torres Strait Islander descent. The purpose of this
      study is to explain the relationship between food insecurity and Aboriginal and
      Torres Islander status in the state of Victoria. METHODS: Data were obtained from
      the 2008 Victorian Population Health Survey; a cross-sectional landline computer
      assisted telephone interview survey of 34,168 randomly selected Victorians aged
      18 years and older; including 339 Aboriginal and Torres Strait Islanders. We
      categorised a respondent as food insecure, if in the previous 12 months, they
      reported having run out of food and not being able to afford to buy more. We used
      multivariable logistic regression to adjust for age, sex, socioeconomic status
      (household income), lifestyle risk factors (smoking, alcohol consumption and
      obesity), social support (ability to get help from family, friends or
      neighbours), household composition (lone parent status, household with a child,
      and household size), and geographic location (rurality). RESULTS: Aboriginal and
      Torres Strait Islanders (20.3%) were more likely than their non-Aboriginal and
      Torres Strait Islander counterparts (5.4%) to have experienced food insecurity;
      odds ratio (OR) = 4.5 (95% CI; 2.7-7.4). Controlling for age, SES, smoking,
      obesity and inability to get help from family or friends reduced the odds ratio
      by 38%; OR(adjusted) = 2.8 (1.6-5.0). CONCLUSIONS: Social determinants and
      lifestyle risk factors only partially explained the higher prevalence of food
      insecurity among Aboriginal and Torres Strait Islanders in Victoria. Further
      research is needed to explain the disparity in food insecurity between the two
      populations in order to inform and guide corrective action.

PMID- 24924600
TI  - Reconstruction of the South Atlantic Subtropical Dipole index for the past 12,000
      years from surface temperature proxy.
AB  - Climate indices based on sea surface temperature (SST) can synthesize information
      related to physical processes that describe change and variability in continental
      precipitation from floods to droughts. The South Atlantic Subtropical Dipole
      index (SASD) is based on the distribution of SST in the South Atlantic and fits
      these criteria. It represents the dominant mode of variability of SST in the
      South Atlantic, which is modulated by changes in the position and intensity of
      the South Atlantic Subtropical High. Here we reconstructed an index of the South
      Atlantic Ocean SST (SASD-like) for the past twelve thousand years (the Holocene
      period) based on proxy-data. This has great scientific implications and important
      socio-economic ramifications because of its ability to infer variability of
      precipitation and moisture over South America where past climate data is limited.
      For the first time a reconstructed index based on proxy data on opposite sides of
      the SASD-like mode is able to capture, in the South Atlantic, the significant
      cold events in the Northern Hemisphere at 12.9-11.6 kyr BP and 8.6-8.0 ky BP.
      These events are related, using a transient model simulation, to precipitation
      changes over South America.

PMID- 24924599
TI  - Cytokinin levels and signaling respond to wounding and the perception of
      herbivore elicitors in Nicotiana attenuata.
AB  - Nearly half a century ago insect herbivores were found to induce the formation of
      green islands by manipulating cytokinin (CK) levels. However, the response of the
      CK pathway to attack by chewing insect herbivores remains unclear. Here, we
      characterize the CK pathway of Nicotiana attenuata (Torr. ex S. Wats.) and its
      response to wounding and perception of herbivore-associated molecular patterns
      (HAMPs). We identified 44 genes involved in CK biosynthesis, inactivation,
      degradation, and signaling. Leaf wounding rapidly induced transcriptional changes
      in multiple genes throughout the pathway, as well as in the levels of CKs,
      including isopentenyladenosine and cis-zeatin riboside; perception of HAMPs
      present in the oral secretions (OS) of the specialist herbivore Manduca sexta
      amplified these responses. The jasmonate pathway, which triggers many herbivore
      induced processes, was not required for these HAMP-triggered changes, but rather
      suppressed the CK responses. Interestingly CK pathway changes were observed also
      in systemic leaves in response to wounding and OS application indicating a role
      of CKs in mediating long distance systemic processes in response to herbivory.
      Since wounding and grasshopper OS elicited similar accumulations of CKs in
      Arabidopsis thaliana L., we propose that CKs are integral components of wounding
      and HAMP-triggered responses in many plant species. 

PMID- 24924601
TI  - Small proteins, big roles: the signaling protein Apela extends the complexity of
      developmental pathways in the early zebrafish embryo.
AB  - The identification of molecules controlling embryonic patterning and their
      functional analysis has revolutionized the fields of Developmental and Cell
      Biology. The use of new sequence information and modern bioinformatics tools has
      enriched the list of proteins that could potentially play a role in regulating
      cell behavior and function during early development. The recent application of
      efficient methods for gene knockout in zebrafish has accelerated the functional
      analysis of many proteins, some of which have been overlooked due to their small
      size. Two recent publications report on the identification of one such protein
      and its role in zebrafish embryogenesis. The protein, currently designated Apela,
      was shown to act as a secreted protein whose absence adversely affected various
      early developmental processes. Additional signaling proteins that have been
      identified in one of the studies are likely to open the way to unraveling
      hitherto unknown developmental pathways and have the potential to provide a more
      comprehensive understanding of known developmental processes. 

PMID- 24924602
TI  - Prevalence of musculoskeletal disorders and rheumatic diseases in an urban
      community in Monagas State, Venezuela: a COPCORD study.
AB  - The aim of the study was to determine the prevalence of musculoskeletal disorders
      and rheumatic diseases in an urban community in Venezuela. We conducted a cross
      sectional, community-based study using the COPCORD (Community Oriented Program
      for Control of Rheumatic Diseases) methodology in subjects older than 18 years.
      Positive cases were evaluated by rheumatologists. We surveyed 3,973 individuals
      (1,606 males and 2,367 females), with a mean age of 43.7 years (standard
      deviation (SD) 17.6). Mean duration of education was 8.9 years (SD 3.7), 79.2 %
      had a monthly income of < US$569, and 46.4 % were working. Excluding trauma, the
      prevalence of pain in the 7 days prior to interview was 19.9 % (95 % confidence
      interval (CI) 18.7-21.2 %). Mean pain intensity on a visual analog scale was 6.3
      (SD 2.2), and 30.1 % (95 % CI 28.7-31.6 %) had a history of pain. Respondents
      reported pain in the knees, back, hands, shoulders, and ankles in the last 7
      days; 4.7 % described current functional limitation, with 16.5 % reporting
      limitations in the past. Regarding treatment, 23.9 % received medication, 6.4 %
      received physical therapy, and 2.6 % received alternative treatment. The main
      diagnoses were osteoarthritis in 15.0 % (95 % CI 13.9-16.1 %), rheumatic regional
      pain syndromes in 6.3 % (95 % CI 5.5-7.1 %), back pain in 2.8 % (95 % CI 2.3-3.4
      %), rheumatoid arthritis in 0.4 % (95 % CI 0.2-0.6 %), crystal arthropathy in 0.3
      % (95 % CI 0.1-0.5 %), fibromyalgia in 0.2 % (95 % CI 0.1-0.4 %), and systemic
      lupus erythematosus in 0.07 % (95 % CI 0.01-0.2 %). The prevalence of
      musculoskeletal disorders was 22.4 %, and the most prevalent disease was
      osteoarthritis. Pain, in which a patient is receiving treatment for
      musculoskeletal disorders, and physical disability were associated with the
      presence of a rheumatic disease.

PMID- 24924604
TI  - Characteristics of seroconversion and implications for diagnosis of post
      treatment Lyme disease syndrome: acute and convalescent serology among a
      prospective cohort of early Lyme disease patients.
AB  - Two-tier serology is often used to confirm a diagnosis of Lyme disease. One
      hundred and four patients with physician diagnosed erythema migrans rashes had
      blood samples taken before and after 3 weeks of doxycycline treatment for early
      Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were
      interpreted according to the 2-tier antibody testing criteria proposed by the
      Centers for Disease Control and Prevention. Serostatus was compared across
      several clinical and demographic variables both pre- and post-treatment. Forty
      one patients (39.4%) were seronegative both before and after treatment. The
      majority of seropositive individuals on both acute and convalescent serology had
      a positive IgM western blot and a negative IgG western blot. IgG seroconversion
      on western blot was infrequent. Among the baseline variables included in the
      analysis, disseminated lesions (p < 0.0001), a longer duration of illness (p <
      0.0001), and a higher number of reported symptoms (p = 0.004) were highly
      significantly associated with positive final serostatus, while male sex (p =
      0.05) was borderline significant. This variability, and the lack of
      seroconversion in a subset of patients, highlights the limitations of using
      serology alone in identifying early Lyme disease. Furthermore, these findings
      underline the difficulty for rheumatologists in identifying a prior exposure to
      Lyme disease in caring for patients with medically unexplained symptoms or
      fibromyalgia-like syndromes.

PMID- 24924603
TI  - Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in
      patients with knee osteoarthritis: a randomized controlled non-inferiority trial.
AB  - This study is aimed at comparing the efficacy and safety of loxoprofen sodium
      hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee
      osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a
      randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority
      trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for
      a 4-week treatment. The primary efficacy endpoint was the proportion of patients
      with an overall improvement of >=50%, and the secondary efficacy endpoint was the
      proportion of patients with an improvement of >=25% from baseline in each of the
      seven main symptoms. The non-inferiority trial was based on a power of 80% and
      significance level of 2.5% with a non-inferiority margin of -10%. In both
      intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as
      LX-T in regard to the primary endpoint. In the ITT analysis, the difference
      between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No
      significant differences were found between the two groups in any of the secondary
      efficacy outcomes. A lower incidence of adverse events was observed in LX-P
      group; however, the difference was not statistically significant. No serious
      adverse events were reported in the LX-P group, whereas one case was reported in
      LX-T group. Based on the present study, topical loxoprofen patch was non-inferior
      to oral loxoprofen in patients with knee osteoarthritis.

PMID- 24924605
TI  - The impact of familial Mediterranean fever on reproductive system.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis,
      or erysipelas-like skin lesion. FMF is the most common periodic febrile syndrome
      affecting more than 150,000 people worldwide. The majority of patients develop
      FMF before the age of 20. FMF may cause amyloidosis, which mainly affects the
      kidneys but may also be accumulated in other organs such as the heart,
      gastrointestinal tract, and reproductive organs. FMF being a systemic disorder
      with a risk for amyloidosis, affecting patients in their childbearing years, and
      with its lifelong colchicine therapy raises concern about its effect on the
      reproductive system. In this article, we review the impact of FMF and its
      treatment to the reproductive system of male and female patients, pregnancy, and
      lactation. 

PMID- 24924606
TI  - Cytochrome P450 interactions and clinical implication in rheumatology.
AB  - There are many potential drug interactions that involve the complex cytochromes
      P450 (CYP) enzyme system when treatments for chronic inflammatory rheumatic
      diseases are used. This iatrogenic risk is increased in patients taking multiple
      drugs such as those with rheumatoid arthritis or gout, whatever the type of CYP
      interaction (substrate, inducer, or inhibitor of one of the CYP isoenzymes). Some
      of these CYP interactions may have clinical consequences, sometimes serious
      (overdose or therapeutic failure) and are often unrecognized by clinicians. The
      aim of this article is first of all to act as a reminder of the metabolic role of
      membrane-bound CYP enzymes in the liver in the oxidation of drugs and the
      potential types of interaction (drug substrate, inducer, or inhibitor or
      indirectly by the modulation of CYP activity through its powerful
      antiinflammatory activity). Secondly, the different factors that modulate the
      enzymatic activity of CYP will be described that may contribute to variations in
      drug metabolism and therefore modify the benefit-risk ratio of the drug. Thirdly,
      an analysis based on a review of the literature will present the different known
      interactions via CYP for drugs used in clinical practice in rheumatic diseases:
      analgesics, antiinflammatory drugs, conventional disease-modifying antirheumatic
      drugs and biologic agents. To limit the clinical consequences of these CYP
      interactions, it is recommended to focus on drugs that are really essential, to
      systematically identify the rheumatic patients most at risk before prescribing,
      and thus to adopt therapeutic strategies that reduce iatrogenic risk. 

PMID- 24924608
TI  - Modifications of open field and novelty behaviours by hippocampal and amygdaloid
      lesions in two inbred strains of mice: Lack of strain * lesion interactions.
AB  - C57BL/6 (C57) and DBA/2 (DBA) mice with dorsal hippocampus, central amygdala and
      sham lesions were observed for an eight-minute period, repeated on three
      consecutive days, in an open field situation with a novel object. Strain
      dependent differences emerged when comparing sham lesioned mice; higher rearing
      and grooming scores as well as more defecation boli were found in DBA. In both
      strains, hippocampal lesions enhanced locomotor activity in the open field while
      amygdaloid lesions increased the number of contacts with the novel object. No
      significant lesion * strain interaction was recorded for any of the behaviours
      analyzed in the open field of the novelty situation. Significant strain * day,
      lesion * day and strain * lesion * day interactions were found thus indicating
      that previously described strain or lesion main effects were more pronounced on a
      particular day of testing. Despite the behavioural differences shown by sham
      lesioned C57 and DBA mice, the effects of the lesions differ in intensity but
      generally go in the same direction whatever the strain considered. Thus, while a
      strain-dependent selective involvement of subcortical areas in associative
      spatial learning has been previously reported, this does not seem to be the case
      for non-associative forms of learning. 

PMID- 24924607
TI  - 25-Hydroxy vitamin D and its relationship with clinical and laboratory parameters
      in patients with rheumatoid arthritis.
AB  - The objective of this study is to evaluate the prevalence of vitamin D
      insufficiency in patients with rheumatoid arthritis (RA) and its association with
      disease activity, severity and physical disability. We included patients with
      rheumatoid arthritis followed in Rheumatology Department of Hassan II University
      Hospital, Fez, Morocco. Patients suffering from liver and kidney insufficiency
      and those who had received vitamin D in the previous 12 months have been
      excluded. Statistical analysis was done using SPSS v 18. A bivariate analysis and
      logistic regression were used to identify factors associated with vitamin D
      deficiency. One hundred seventy patients were included with a mean age of 50 +/-
      12.1 [17-83] years, and a female predominance (88.1%). All of our patients had
      hypovitaminosis D. The prevalence of 25(OH)-D insufficiency and deficiency was
      64.5 and 35.5% successively. In unadjusted analysis, vitamin D concentration was
      inversely associated with pain visual analog scale VAS score (p < 0.001),
      asthenia VAS (p < 0.001), morning stiffness (p = 0.03), number of tender joints
      (p = 0.004), number of swollen joints (p < 0.001), inflammatory markers (p =
      0,012), Disease Activity Score (p = 0.009), physical disability using Health
      Assessment Questionnaire (HAQ) (p = 0.001), and severity of the disease (p <
      0.001). After logistic regression persisted association with female sex (OR =
      4.3, CI = [0.94 to 20.976], p = 0.05), asthenia VAS (OR = 1.029, CI = [1.011 to
      1.046], p = 0.001), and with the severity of the disease (OR = 2.910, CI = [1.314
      6.441], p = 0.008). The vitamin D deficiency is common in our patients with RA.
      This deficiency is associated with female sex, severe asthenia, and the severity
      of the disease.

PMID- 24924609
TI  - Reactions of staggerer and non-mutant male mice to female urine and vaginal
      secretion odors.
AB  - Previous studies have shown that staggerer male mice do not copulate
      spontaneously. When meeting unfamiliar non-mutant females either in estrus or in
      anestrus condition, these neurological mutants behave similarly. One possible
      explanation is that staggerer males are unable to detect female odors. To test
      this hypothesis, male reactions to urine and vaginal secretions of females,
      either in estrous or in anestrous, were studied in a circular device allowing
      mutant and non-mutant males to move and to explore sources of odors during 20
      minutes. Concerning vaginal secretions odors, the duration of time spent in
      different sectors by mutants was identical for both conditions of female sexual
      receptivity whereas non-mutant males spent more time on location with vaginal
      secretions of estrus females. For non-mutant and mutant males as well, duration
      of time spent in sectors with urine odors was similar for both conditions of
      female sexual receptivity. We hypothetised a possible deficiency for social odor
      detection and/or integration due to the staggerer mutation. 

PMID- 24924610
TI  - Effect of chronic exposure to a magnetic field on two forms of murine aggression.
AB  - The effect of continuous exposure to a relatively strong magnetic field for about
      3-4 weeks were evaluated on social (inter-male) aggression in isolated males and
      on maternal attack by lactating female mice. This study revealed that exposure to
      intense fields produced a significant reduction in social and maternal aggression
      towards anosmic (passive) standard opponent intruders. The detailed ethologically
      assessed results indicate that such exposure produces a significant decline in
      most behavioural categories recorded throughout this study in isolated male and
      lactating female mice. Defensive behaviour, however, seemed enhanced in lactating
      mice. These results may be explained in terms of the magnetic fields interfering
      with the function of the central nervous system or the physiological substrates
      which control such types of behaviour. 

PMID- 24924611
TI  - Queen attractivity in the Argentine ant Iridomyrmex humilis (Mayr).
AB  - The origin of queen attractivity in the Argentine ant was estimated by presenting
      body parts (head, thorax, abdomen) of dead queens to workers. Whatever the
      preparation, crushed or intact, the thorax was always significantly more
      attractive than other parts of the body. The legs seemed to be highly attractive
      to the workers, mainly through lactile stimuli. The results are discussed with
      regards to the occurrence of thoracic glands. 

PMID- 24924612
TI  - Odor discrimination and dominance in male domestic guinea pigs.
AB  - Do male guinea pigs (Cavia porcellus), with established positions in social
      dominance hierarchies, discriminate subordinate and dominant animals based upon
      odor cues from the perineal sac glandular complex? Six groups of three or four
      males were tested first to establish within-group dominance status and second for
      responses to cotton swabs that had been wiped with the perineal sac glandular
      complex of other males in the group. There was a significant (P < 0.05) linear
      relationship between aggressive responses to the cotton swabs and dominance ranks
      of the males (y = -0.16x + 0.86). Dominance may influence sebum production in the
      perineal sac glandular complex of guinea pigs via a mechanism involving
      androgens. Discrimination of dominance status could function in terms of male
      spatial relations, avoidance of areas inhabited by dominant individuals, and
      possibly in terms of female mate selection. 

PMID- 24924613
TI  - Theoretical possibility of a genetic assimilation of the feeeing direction in
      Talitrus saltator.
AB  - Reports on the genetic assimilation of features involving behaviour are very
      scarce, while they are more common in the fields of morphology and physiology.
      This paper investigates the theoretical possibility of a genetic assimilation of
      the 'fleeing direction' in the sandhopper (Talitrus saltator), consistent with
      Bateson's model of genetic assimilation. This is done from the two simple genetic
      determinations suggested by L. Pardi and F. Scapini to explain the variability of
      the feature between populations. The conditions for this genetic assimilation to
      occur are examined and particular attention is paid to the differences between
      the properties of the two determinations. Finally, the possible importance of
      genetic assimilation in the field of animal orientation is discussed. 

PMID- 24924614
TI  - Removal of vibrissae in male mice does not influence social dominance.
AB  - The hypothesis was tested that vibrissae in male mice are essential in the
      development of social dominance. Male mice were either sham-treated or de
      whiskered and then housed in groups of either three or two animals. To determine
      dominance, three different methods were used: behavioural observations, food
      deprivation tests and tube tests. It was found that the intact mice did not
      become dominant more often than the de-whiskered mice, indicating that removal of
      vibrissae does not influence the social status of mice. The outcomes of the three
      tests did not correlate, probably because they measure different aspects of
      dominance. 

PMID- 24924616
TI  - Synthesis of heterocycles through transition-metal-catalyzed isomerization
      reactions.
AB  - Metal-catalyzed isomerization of N- and O-allylic systems is emerging as an
      effective method to form synthetically useful iminium and oxocarbenium
      intermediates. In the presence of tethered nucleophiles, several recent examples
      illuminate this approach as a powerful strategy for the synthesis of structurally
      complex and diverse heterocycles. In this Concept article, we attempt to cover
      this area of research through a selection of recent versatile examples. 

PMID- 24924617
TI  - Nano carriers that enable co-delivery of chemotherapy and RNAi agents for
      treatment of drug-resistant cancers.
AB  - Tumor cells exhibit drug resistant phenotypes that decrease the efficacy of
      chemotherapeutic treatments. The drug resistance has a genetic basis that is
      caused by an abnormal gene expression. There are several types of drug
      resistance: efflux pumps reducing the cellular concentration of the drug,
      alterations in membrane lipids that reduce cellular uptake, increased or altered
      drug targets, metabolic alteration of the drug, inhibition of apoptosis, repair
      of the damaged DNA, and alteration of the cell cycle checkpoints (Gottesman et
      al., 2002; Holohan et al., 2013). siRNA is used to silence the drug resistant
      phenotype and prevent this drug resistance response. Of the listed types of drug
      resistance, pump-type resistance (e.g., high expression of ATP-binding cassette
      transporter proteins such as P-glycoproteins (Pgp; also known as multi-drug
      resistance protein 1 or MDR1, encoded by the ATP-Binding Cassette Sub-Family B
      Member 1 (ABCB1) gene)) and apoptosis inhibition (e.g., expression of anti
      apoptotic proteins such as Bcl-2) are the most frequently targeted for gene
      silencing. The co-delivery of siRNA and chemotherapeutic drugs has a synergistic
      effect, but many of the current projects do not control the drug release from the
      nanocarrier. This means that the drug payload is released before the drug
      resistance proteins have degraded and the drug resistance phenotype has been
      silenced. Current research focuses on cross-linking the carrier's polymers to
      prevent premature drug release, but these carriers still rely on environmental
      cues to release the drug payload, and the drug may be released too early. In this
      review, we studied the release kinetics of siRNA and chemotherapeutic drugs from
      a broad range of carriers. We also give examples of carriers used to co-deliver
      siRNA and drugs to drug-resistant tumor cells, and we examine how modifications
      to the carrier affect the delivery. Lastly, we give our recommendations for the
      future directions of the co-delivery of siRNA and chemotherapeutic drug
      treatments. 

PMID- 24924618
TI  - Aldehyde tag coupled with HIPS chemistry enables the production of ADCs
      conjugated site-specifically to different antibody regions with distinct in vivo
      efficacy and PK outcomes.
AB  - It is becoming increasingly clear that site-specific conjugation offers
      significant advantages over conventional conjugation chemistries used to make
      antibody-drug conjugates (ADCs). Site-specific payload placement allows for
      control over both the drug-to-antibody ratio (DAR) and the conjugation site, both
      of which play an important role in governing the pharmacokinetics (PK),
      disposition, and efficacy of the ADC. In addition to the DAR and site of
      conjugation, linker composition also plays an important role in the properties of
      an ADC. We have previously reported a novel site-specific conjugation platform
      comprising linker payloads designed to selectively react with site-specifically
      engineered aldehyde tags on an antibody backbone. This chemistry results in a
      stable C-C bond between the antibody and the cytotoxin payload, providing a
      uniquely stable connection with respect to the other linker chemistries used to
      generate ADCs. The flexibility and versatility of the aldehyde tag conjugation
      platform has enabled us to undertake a systematic evaluation of the impact of
      conjugation site and linker composition on ADC properties. Here, we describe the
      production and characterization of a panel of ADCs bearing the aldehyde tag at
      different locations on an IgG1 backbone conjugated using Hydrazino-iso-Pictet
      Spengler (HIPS) chemistry. We demonstrate that in a panel of ADCs with aldehyde
      tags at different locations, the site of conjugation has a dramatic impact on in
      vivo efficacy and pharmacokinetic behavior in rodents; this advantage translates
      to an improved safety profile in rats as compared to a conventional lysine
      conjugate. 

PMID- 24924620
TI  - Potential role of fibrosis imaging in severe valvular heart disease.

PMID- 24924619
TI  - Circulating levels of liver enzymes and incidence of atrial fibrillation: the
      Atherosclerosis Risk in Communities cohort.
AB  - BACKGROUND: Elevated levels of circulating liver enzymes have been associated
      with increased risk of cardiovascular disease. Their possible association with
      atrial fibrillation (AF) has received little attention. METHODS: We studied 9333
      men and women, aged 53-75 years, free of AF, participating in the Atherosclerosis
      Risk in Communities Study followed-up from 1996 to 2010. Aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl
      transpeptidase (GGT) were measured in stored plasma samples. Incident AF was
      ascertained from hospitalisations and death certificates. Associations between
      liver enzymes and AF incidence were assessed using multivariable Cox proportional
      hazards models. RESULTS: During a mean follow-up of 12 years, 1021 incident AF
      events were identified. Levels of AST, and to a lesser extent ALT, showed a U
      shaped association with AF risk, with higher AF risk among individuals in the two
      extremes of the distribution in minimally adjusted models. The associations were
      weakened after adjustment for potential confounders. By contrast, GGT, modelled
      as log base 2, was linearly associated with AF risk after multivariable
      adjustment: a doubling of GGT levels was associated with a 20% increased risk of
      AF (95% CI 10% to 30%). Additional adjustment for inflammatory markers did not
      appreciably affect the results. Associations were not different in men and women,
      in whites and blacks, among never drinkers of alcohol, and among those without
      prevalent heart failure. CONCLUSIONS: In this community-based prospective study,
      higher levels of liver enzymes, mainly GGT, were associated with an increased
      risk of AF. The mechanisms underlying this association deserve further scrutiny.

PMID- 24924621
TI  - Heart failure treatment in adults with congenital heart disease: where do we
      stand in 2014?
AB  - Heart failure (HF) is the leading cause of death in adults with repaired
      congenital heart disease (CHD). However there is currently little evidence to
      guide treatment strategies in this growing group of patients. Unlike the majority
      of HF, which is usually caused by LV systolic or diastolic dysfunction, CHD-HF is
      more often a consequence of RV disease, valve dysfunction, shunting or pulmonary
      hypertension. It is therefore not appropriate to extrapolate from the acquired HF
      literature and apply it to this heterogeneous population of CHD patients.
      Additionally, patients with CHD have been excluded from most large trials of
      medical or device therapy of HF, which has resulted in small retrospective and
      underpowered studies in the CHD population. This article critically reviews the
      current knowledge about CHD-HF, paying particular attention to medical therapy in
      different CHD populations, cardiac resynchronisation therapy and implantable
      cardiac defibrillators, and the challenges of heart transplantation and
      mechanical circulatory support in CHD patients. 

PMID- 24924624
TI  - Erratum to: Perinatal Distress in Women in Low- and Middle-Income Countries:
      Allostatic Load as a Framework to Examine the Effect of Perinatal Distress on
      Preterm Birth and Infant Health.

PMID- 24924622
TI  - Early warning of West Nile virus mosquito vector: climate and land use models
      successfully explain phenology and abundance of Culex pipiens mosquitoes in north
      western Italy.
AB  - BACKGROUND: West Nile Virus (WNV) is an emerging global health threat.
      Transmission risk is strongly related to the abundance of mosquito vectors,
      typically Culex pipiens in Europe. Early-warning predictors of mosquito
      population dynamics would therefore help guide entomological surveillance and
      thereby facilitate early warnings of transmission risk. METHODS: We analysed an
      11-year time series (2001 to 2011) of Cx. pipiens mosquito captures from the
      Piedmont region of north-western Italy to determine the principal drivers of
      mosquito population dynamics. Linear mixed models were implemented to examine the
      relationship between Cx. pipiens population dynamics and environmental predictors
      including temperature, precipitation, Normalized Difference Water Index (NDWI)
      and the proximity of mosquito traps to urban areas and rice fields. RESULTS: Warm
      temperatures early in the year were associated with an earlier start to the
      mosquito season and increased season length, and later in the year, with
      decreased abundance. Early precipitation delayed the start and shortened the
      length of the mosquito season, but increased total abundance. Conversely,
      precipitation later in the year was associated with a longer season. Finally,
      higher NDWI early in the year was associated with an earlier start to the season
      and increased season length, but was not associated with abundance. Proximity to
      rice fields predicted higher total abundance when included in some models, but
      was not a significant predictor of phenology. Proximity to urban areas was not a
      significant predictor in any of our models. Predicted variations in start of the
      season and season length ranged from one to three weeks, across the measured
      range of variables. Predicted mosquito abundance was highly variable, with
      numbers in excess of 1000 per trap per year when late season temperatures were
      low (average 21 degrees C) to only 150 when late season temperatures were high
      (average 30 degrees C). CONCLUSIONS: Climate data collected early in the year, in
      conjunction with local land use, can be used to provide early warning of both the
      timing and magnitude of mosquito outbreaks. This potentially allows targeted
      mosquito control measures to be implemented, with implications for prevention and
      control of West Nile Virus and other mosquito borne diseases.

PMID- 24924625
TI  - Social value of a quality-adjusted life year (QALY) in Spain: the point of view
      of oncologists.
AB  - PURPOSE: The economic situation showed that the resources devoted to health
      spending are limited, making rationalisation of their consumption necessary. The
      relevance of pharmacoeconomic analyses is becoming crucial. The ECO Foundation,
      promoting the quality of oncology care, set out to analyse the consensus on the
      new therapeutic targets inclusion and the integration of pharmacoeconomics when
      evaluating their effectiveness. METHODS: Study about pharmacoeconomic estimations
      was performed during the first ECO-Seminar (2010). It was developed using a
      modified Delphi method, in four stages: (1) committee coordinator establishment,
      (2) expert-panel selection, (3) preparation and submission of survey (1 question)
      by email, and (4) analysis of the degree of consensus reached. RESULTS: Results
      were obtained from surveys completed by 35 experts. Regarding the tolerable
      annual cost for the approval of new drugs, 68.8 % of the respondents considered a
      cost per quality-adjusted life year (QALY) gained between ?30,000 and 100,000
      acceptable (34.4 % ?30,000-60,000; 34.4 % ?60,000-100,000), 21.9 % of the
      respondents found costs between ?100,000-150,000/QALY and 9.3 % of the
      respondents found costs above ?150,000/QALY acceptable. CONCLUSIONS: The costs of
      new drugs are higher than traditional treatments, making it a priority to
      identify subgroups of patients with specific molecular profiles as candidates for
      higher-efficiency-targeted therapies. The allocation of the available resources
      to the most effective interventions, to achieve the best clinical outcomes with
      lower costs and best subjective profile possible, allows expenditure to be
      rationalised. Pharmacoeconomic studies are a basic tool for obtaining better
      health outcomes according to the available resources, while also considering the
      other needs of the population.

PMID- 24924626
TI  - Risk-cost-benefit analysis for transportation corridors with interval
      uncertainties of heterogeneous data.
AB  - Access management, which systematically limits opportunities for egress and
      ingress of vehicles to highway lanes, is critical to protect trillions of dollars
      of current investment in transportation. This article addresses allocating
      resources for access management with incomplete and partially relevant data on
      crash rates, travel speeds, and other factors. While access management can be
      effective to avoid crashes, reduce travel times, and increase route capacities,
      the literature suggests a need for performance metrics to guide investments in
      resource allocation across large corridor networks and several time horizons. In
      this article, we describe a quantitative decision model to support an access
      management program via risk-cost-benefit analysis under data uncertainties from
      diverse sources of data and expertise. The approach quantifies potential
      benefits, including safety improvement and travel time savings, and costs of
      access management through functional relationships of input parameters including
      crash rates, corridor access point densities, and traffic volumes. Parameter
      uncertainties, which vary across locales and experts, are addressed via numerical
      interval analyses. This approach is demonstrated at several geographic scales
      across 7,000 kilometers of highways in a geographic region and several
      subregions. The demonstration prioritizes route segments that would benefit from
      risk management, including (i) additional data or elicitation, (ii) right-of-way
      purchases, (iii) restriction or closing of access points, (iv) new alignments,
      (v) developer proffers, and (vi) etc. The approach ought to be of wide interest
      to analysts, planners, policymakers, and stakeholders who rely on heterogeneous
      data and expertise for risk management. 

PMID- 24924628
TI  - Active vitamin D possesses beneficial effects on the interaction between muscle
      and bone.
AB  - Vitamin D deficiency and advanced glycation end products (AGEs) are suggested to
      be involved in the pathogenesis of osteoporosis and sarcopenia. However, the
      effects of vitamin D and AGEs on myogenesis and the interaction between muscle
      and bone remains still unclear. We previously showed that osteoglycin (OGN) is
      secreted from myoblasts and stimulates osteoblastic differentiation, suggesting
      that it plays important roles in the interaction between muscle and bone. The aim
      of this study is thus to examine the effects of vitamin D and AGEs on myoblastic
      differentiation of C2C12 cells and osteoblastic differentiation of osteoblastic
      MC3T3-E1 cells through OGN expression. 1alpha,25-dihydroxyvitamin D3 (1,25D) and
      eldecalcitol, an active vitamin D analog, induced the expression of MyoD,
      myogenin and OGN, and these effects were abolished by vitamin D receptor (VDR)
      suppression by siRNA in C2C12 cells. Moreover, conditioned medium from 1,25D
      pretreated C2C12 cells stimulated the expression of type 1 collagen and alkaline
      phosphatase in MC3T3-E1 cells, compared to control medium from 1,25D-untreated
      C2C12 cells. In contrast, conditioned medium from VDR-suppressed and 1,25D
      pretreated C2C12 cells showed no effects. AGE2 and AGE3 suppressed the expression
      of MyoD, myogenin and OGN in C2C12 cells. Moreover, 1,25D blunted the AGEs'
      effects. In conclusion, these findings showed for the first time that active
      vitamin D plays important roles in myogenesis and muscle-induced
      osteoblastogenesis through OGN expression. Active vitamin D treatment may rescue
      the AGEs-induced sarcopenia as well as - suppressed osteoblastic differentiation
      via OGN expression in myoblasts. 

PMID- 24924627
TI  - TCR-induced, PKC-theta-mediated NF-kappaB activation is regulated by a caspase-8
      caspase-9-caspase-3 cascade.
AB  - It has been documented that caspase-8, a central player in apoptosis, is also
      crucial for TCR-mediated NF-kappaB activation. However, whether other caspases
      are also involved this process is unknown. In this report, we showed that in
      addition to caspase-8, caspase-9 is required for TCR-mediated NF-kappaB
      activation. Caspase-9 induces activation of PKC-theta, phosphorylation of Bcl10
      and NF-kappaB activation in a caspase-3-dependent manner, but it appears that
      Bcl10 phosphorylation is uncoupled from NF-kappaB activation. Furthermore,
      caspase-8 lies upstream of caspase-9 during T cell activation. Therefore, TCR
      ligation elicits a caspase cascade involving caspase-8, caspase-9 and caspase-3
      which initiates PKC-theta-dependent pathway leading to NF-kappaB activation and
      PKC-theta-independent Bcl10 phosphorylation which limits NF-kB activity. 

PMID- 24924629
TI  - Eph receptor A10 has a potential as a target for a prostate cancer therapy.
AB  - We recently identified Eph receptor A10 (EphA10) as a novel breast cancer
      specific protein. Moreover, we also showed that an in-house developed anti-EphA10
      monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer
      cells, suggesting EphA10 as a promising target for breast cancer therapy.
      However, the only other known report for EphA10 was its expression in the testis
      at the mRNA level. Therefore, the potency of EphA10 as a drug target against
      cancers other than the breast is not known. The expression of EphA10 in a wide
      variety of cancer cells was studied and the potential of EphA10 as a drug target
      was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was
      overexpressed in breast cancer cell lines as well as in prostate and colon cancer
      cell lines. Thus, we focused on prostate cancers in which EphA10 expression was
      equivalent to that in breast cancers. As a result, EphA10 expression was clearly
      shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and
      protein levels. In order to evaluate the potential of EphA10 as a drug target, we
      analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found
      that significant cytotoxicity was mediated by the expression of EphA10.
      Therefore, the idea was conceived that the overexpression of EphA10 in prostate
      cancers might have a potential as a target for prostate cancer therapy, and
      formed the basis for the studies reported here. 

PMID- 24924630
TI  - Cholesterol depletion induces ANTXR2-dependent activation of MMP-2 via ERK1/2
      phosphorylation in neuroglioma U251 cell.
AB  - Cholesterol is a critical component of lipid rafts implicated in regulating
      multiple signal transduction. The anthrax toxin receptor 2 (ANTXR2) is a type I
      membrane protein acting as the second receptor for the anthrax toxin. In this
      study, we first investigated the association between cholesterol and ANTXR2. We
      provided the evidence that cholesterol depletion by methyl-beta-cyclodextrin
      (MbetaCD) promoted ANTXR2 expression in U251 neuroglioma cell, which was reversed
      by cholesterol supplement. MbetaCD-induced ANTXR2 up-regulation contributed to
      ERK1/2 phosphorylation, which was responsible for MT1-MMP and MMP-2 activation.
      Our data suggested that cellular cholesterol regulated ANTXR2-dependent
      activation of MMP-2 via ERK1/2 phosphorylation in neuroglioma U251 cell. 

PMID- 24924631
TI  - Palmitate induces SHIP2 expression via the ceramide-mediated activation of NF
      kappaB, and JNK in skeletal muscle cells.
AB  - AIMS: Elevated plasma free fatty acids impair the insulin signaling by induction
      of the expression of protein phosphatases. However, the effect of palmitate on
      SH2-containing inositol 5'-phosphatase 2 (SHIP2) expression has not been
      investigated. Here we investigated the effects of palmitate on SHIP2 expression
      and elucidated the underlying mechanisms in skeletal muscle cells. MAIN METHODS:
      SHIP2 mRNA and protein levels were measured in C2C12 myotubes exposed to
      palmitate. Specific inhibitors were used to identify the signaling pathways
      involved in SHIP2 expression. KEY FINDINGS: The results showed that 0.5mM
      palmitate significantly upregulates the mRNA and protein levels of SHIP2 in C2C12
      cells. To address the role of palmitate intracellular metabolites in SHIP2
      expression, the myotubes were treated with palmitate in the presence of ceramide
      and diacylglycerol synthesis inhibitors. The results demonstrated that only
      ceramide synthesis inhibition could prevent palmitate-induced SHIP2 expression in
      these cells. In addition, the incubation of muscle cells with different
      concentrations of C2-ceramide dose-dependently enhanced SHIP2 expression.
      Furthermore, the inhibition of both JNK and NF-kappaB pathways could prevent
      ceramide-induced SHIP2 expression in myotubes. SIGNIFICANCE: These findings
      suggest that palmitate contributes to SHIP2 overexpression in skeletal muscle via
      the mechanisms involving the activation of ceramide-JNK and NF-kappaB pathways.

PMID- 24924632
TI  - Fatty acid-bearing albumin but not fatty acid-depleted albumin induces HIF-1
      activation in human renal proximal tubular epithelial cell line HK-2.
AB  - Recently, we found that albumin overload induces expression of the transcription
      factor hypoxia-inducible factor-1alpha (HIF-1alpha) protein and several HIF-1
      target genes in human renal proximal tubular epithelial cell line HK-2. In this
      study, the role of albumin-bound fatty acids in the albumin-induced HIF-1
      activation was studied. The enhancing effect of fatty acid-bearing human serum
      albumin [FA(+)HSA] treatment on HIF-1alpha protein expression was much greater
      than that of fatty acid-depleted human serum albumin [FA(-)HSA] treatment. The
      FA(+)HSA treatment induced HIF-1 target gene mRNAs such as those of glucose
      transporter 1 (GLUT1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and
      breast cancer resistance protein (BCRP) in concentration-dependent manners, while
      FA(-)HSA caused no significant increases in these mRNAs. Consistent with
      increased GLUT1 mRNA, GLUT1 protein expression and GLUT inhibitor cytochalasin B
      sensitive d-[(3)H]glucose uptake activity were significantly enhanced by
      treatment with FA(+)HSA, but not with FA(-)HSA. These findings indicate that
      fatty acids bound to albumin play a crucial role in albumin-induced HIF-1
      activation followed by changes in HIF-1 target gene expression and protein
      product activity. 

PMID- 24924633
TI  - Tetrameric ZBRK1 DNA binding domain has affinity towards cognate DNA in absence
      of zinc ions.
AB  - Zinc finger transcription regulatory proteins play crucial roles in cell-cycle
      regulation, DNA damage response and tumor genesis. Human ZBRK1 is a zinc-finger
      transcription repressor protein, which recognizes double helical DNA containing
      consensus sequences of 5'GGGXXXCAGXXXTTT3'. In the present study, we have
      purified recombinant DNA binding domain of ZBRK1, and studied binding with zinc
      ions and DNA, using biophysical techniques. The elution profile of the purified
      protein suggests that this ZBRK1 forms a homotetramer in solution. Dissociation
      and pull down assays also suggest that this domain forms a higher order oligomer.
      The ZBRK1-DNA binding domain acquires higher stability in the presence of zinc
      ions and DNA. The secondary structure of the ZBRK1-DNA complex is found to be
      significantly altered from the standard B-DNA conformation. 

PMID- 24924634
TI  - Novel elongase of Pythium sp. with high specificity on Delta(6)-18C desaturated
      fatty acids.
AB  - We identified a novel elongase gene from a selected strain of the Oomycete,
      Pythium sp. BCC53698. Using a PCR approach, the cloned gene (PyElo) possessed an
      open reading frame (ORF) of 834 bp encoding 277 amino acid residues. A similarity
      search showed that it had homology with the PUFA elongases of several organisms.
      In addition, the signature characteristics, including four conserved motifs, a
      histidine-rich catalytic motif and membrane-associated feature were present in
      the Pythium gene. Heterologous expression in Saccharomyces cerevisiae showed that
      it was specific for fatty acid substrates, having a double bond at Delta(6)
      position, which included gamma-linolenic acid (GLA) and stearidonic acid (STA),
      and preferentially elongated the n3-18C PUFA. This is an elongase in Oomycete
      fungi, which displays very high specificity on Delta(6)-18C desaturated fatty
      acids. This will be a powerful tool to engineer PUFA biosynthesis in organisms of
      interest through the n-6 series pathway for producing value-added fatty acids.

PMID- 24924635
TI  - A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor
      cells expressing MUC1 in transgenic mice.
AB  - Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell
      growth and negative immunomodulation. We hypothesized that a soluble form of
      Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor
      molecules like human Siglec-9, leading to provide antitumor benefit against MUC1
      expressing tumor, and generated transgenic mouse lines expressing sSiglec-9
      (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally
      transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower
      histological malignancy as compared with non-transgenic mice. The sSiglec-9 was
      detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9
      and MUC1 were often colocalized on surfaces of the tumor cells. PCNA
      immunohistochemistry also revealed the reduced proliferation of the tumor cells
      in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor
      proliferation, MUC1 expressions were tend to be reduced. In the ascites of
      sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas
      aggregations of degenerative T cells were often observed in the non-transgenic
      mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1
      expressing tumor in the transgenic mice, which may avoid the negative
      immunomodulation and/or suppress tumor-associated MUC1 downstream signal
      transduction, and subsequent tumor proliferation. 

PMID- 24924636
TI  - Analysis of subcellular localization and function of the yeast Rab6 homologue,
      Ypt6p, using a novel amino-terminal tagging strategy.
AB  - Ypt6p, the yeast homologue of mammalian Rab6, is involved in the multiple
      processes regulated by membrane trafficking such as vacuole maturation and
      membrane protein recycling. Although several lines of evidence suggest that Ypt6p
      is possibly localized to multiple membrane compartments, the precise localization
      of endogenous Ypt6p remains to be elucidated. In this study, we developed a novel
      method for N-terminal tagging of endogenous protein based on homologous
      recombination and investigated the subcellular localization and function of
      Ypt6p. Ypt6p and its GTP-bound form were predominantly localized to the cis- to
      medial-Golgi compartments whereas the GDP-bound form of Ypt6p was localized to
      the cytosol. Ric1p, a component of the specific GEF complex for Ypt6p, largely
      colocalized with Ypt6p in the early Golgi, and localization of Ypt6p changed to
      the cytosol in ric1Delta cells. On the other hand, Gyp6p, a putative GAP for
      Ypt6p, was localized to the trans-Golgi compartment and deletion of GYP6
      increased the localization of Ypt6p at the trans-Golgi, suggesting that Gyp6p
      promotes the dissociation of Ypt6p from the Golgi when arriving at the trans
      Golgi compartment. Additionally, we demonstrated that overexpression of the GDP
      bound form of Ypt6p caused defective vacuole formation and recycling of Snc1p to
      the plasma membrane. These results suggest that the GTP-binding activity of Ypt6p
      is necessary for intra-Golgi trafficking and protein recycling in the early Golgi
      compartment. 

PMID- 24924637
TI  - Tunable and selective conversion of 5-HMF to 2,5-furandimethanol and 2,5
      dimethylfuran over copper-doped porous metal oxides.
AB  - Tunable and selective hydrogenation of the platform chemical 5
      hydroxymethylfurfural into valuable C6 building blocks and liquid fuel additives
      is achieved with copper-doped porous metal oxides in ethanol. A new catalyst
      composition with improved hydrogenation/hydrogenolysis activity is obtained by
      introducing small amounts of ruthenium dopant into the previously reported
      Cu(0.59) Mg2.34 Al1.00 structure. At a mild reaction temperature (100  degrees
      C), 2,5-furandimethanol is obtained with excellent selectivity up to >99%. Higher
      reaction temperatures (220  degrees C) favor selective deoxygenation to 2,5
      dimethylfuran and minor product 2,5-dimethyltetrahydrofuran with a combined yield
      as high as 81%. Notably, these high product yields are maintained at a substrate
      concentration up to 10 wt% and a low catalyst loading. The influence of different
      alcohol solvents on product selectivity is explored. Furthermore, reaction
      intermediates formed at different reaction temperatures are identified. The
      composition of these product mixtures provides mechanistic insight into the
      nature of the reduction pathways that influence product selectivity. The
      catalysts are characterized by elemental analysis, TEM, and BET techniques before
      and after the reaction. Catalyst recycling experiments are conducted in batch and
      in a continuous-flow setup.

PMID- 24924638
TI  - [Scientific evidence for laparoscopic rectal cancer surgery].
AB  - BACKGROUND: Innovative surgical techniques in colorectal surgery aim to provide
      diminished surgical injury and at least equivalent or even improved quality of
      treatment and oncological results. High level clinical studies are mandatory to
      examine the feasibility and advantages (or disadvantages) of new operative
      techniques. OBJECTIVES: Laparoscopic colonic resection for cancer has been
      investigated with respect to safety and oncological quality in various
      prospective randomized studies (COST study, COLOR-I and CLASICC). The minimally
      invasive procedure is feasible and safe which was demonstrated in many studies
      but can these results be extrapolated to laparoscopic rectal cancer surgery?
      RESULTS: The short term outcomes of the COLOR-II trial were published recently
      and laparoscopic resection for rectal cancer was not found to be inferior
      compared to open resection. Recovery after laparoscopic surgery was better than
      after open surgery. Laparoscopic surgery was found to have significant advantages
      with respect to blood loss, operating time, use of pain medication, early
      restoration of bowel function and reduction of hospital stay as well as the
      lateral safety margins in the distal third of the rectum. The long-term results
      focussing on local recurrence showed a positive trend in favor of laparoscopic
      rectal surgery and will be published shortly. CONCLUSION: Laparoscopic total
      mesorectal excision (TME) appears to have clinically measurable short-term
      advantages in patients with primary rectal cancer based on the evidence of
      randomized studies. Laparoscopic rectal cancer resection may become the gold
      standard in the future.

PMID- 24924639
TI  - [Treatment reality with respect to laparoscopic surgery of colonic cancer in
      Germany].
AB  - BACKGROUND: Prospective randomized studies and meta-analyses have shown that
      laparoscopic resection for colonic cancer is equivalent to open resection with
      respect to the oncological results and has short-term advantages in the early
      postoperative outcome. The aim of this study was to investigate whether
      laparoscopic colonic resection has become established as the standard in routine
      treatment. METHODS: Data from the multicenter observational study "Quality
      assurance colonic cancer (primary tumor)" from the time period from 1 January
      2009 to 21 December 2011 were evaluated with respect to the total proportion of
      laparoscopic colonic cancer resections and tumor localization and specifically
      for laparoscopic sigmoid colon cancer resections. A comparison between low and
      high volume clinics (< 30 versus >= 30 colonic cancer resections/year) was
      carried out. RESULTS: Laparoscopic colonic cancer resections were carried out in
      12 % versus 21.4 % of low and high volume clinics, respectively (p < 0.001) with
      a significant increase for low volume clinics (from 8.0 % to 15.6 %, p < 0.001)
      and a constant proportion in high volume clinics (from 21.7 % to 21.1 %, p =
      0.905). For sigmoid colon cancer laparoscopic resection was carried out in 49.7 %
      versus 47.6 % (p = 0.584). Differences were found between low volume and high
      volume clinics in the conversion rates (17.3 % versus 6.6 %, p < 0.001), the
      length of the resected portion (O 23.6 cm versus 36.0 cm, p < 0.001) and the
      lymph node yield (O n = 15.7 versus 18.2, p = 0.008). There were no differences
      between the two groups of clinics regarding postoperative morbidity and
      mortality. The postoperative morbidity and length of stay were significantly
      lower for laparoscopic sigmoid resection than for conventional sigmoid resection.
      CONCLUSION: The laparoscopic access route for colonic cancer resection is not the
      standard approach in the participating clinics. The laparoscopic access route has
      the highest proportion for sigmoid colon resection. The differences in the
      conversion rates, length of the resected portion and the number of lymph nodes
      investigated between the low volume and high volume clinics must be viewed
      critically and must be interpreted in connection with the long-term oncological
      results.

PMID- 24924641
TI  - High resolution NEXAFS of perylene and PTCDI: a surface science approach to
      molecular orbital analysis.
AB  - We made use of synchrotron radiation to perform near edge X-ray absorption fine
      structure spectroscopy, NEXAFS, at the carbon K-edge of perylene and perylene
      tetracarboxylic-diimide, PTCDI. Reference spectra measured for isolated molecules
      in the gas phase are compared with polarization dependent NEXAFS spectra measured
      on highly oriented thin films in order to study the symmetry of the molecular
      orbitals. The molecular overlayers are grown onto the rutile TiO2(110) surface
      for which the large anisotropic corrugation effectively drives the molecular
      orientation, while its dielectric nature prevents the rehybridization of the
      molecular orbitals. We employed density functional theory, DFT, calculations to
      disentangle the contribution of specific carbon atoms to the molecular density of
      states. Numerical simulations correctly predict the observed NEXAFS azimuthal
      dichroism of the sigma* resonances above the ionization threshold, from which we
      determine the full geometric orientation of the overlayer molecules. A
      discrepancy observed for the spectral contribution of the imide carbon atom to
      the calculated unoccupied molecular orbitals has been explained in terms of
      initial state effects, as determined by Hartree-Fock corrections and in full
      agreement with the corresponding shift of the C 1s core level measured by X-ray
      photoelectron spectroscopy, XPS. 

PMID- 24924640
TI  - Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated
      deletion of exon 6 and 7 account for previously unexplained cases of Marshall
      Smith syndrome.
AB  - Marshall-Smith syndrome (MSS) is a very rare malformation syndrome characterized
      by typical craniofacial anomalies, abnormal osseous maturation, developmental
      delay, failure to thrive, and respiratory difficulties. Mutations in the nuclear
      factor 1/X gene (NFIX) were recently identified as the cause of MSS. In our study
      cohort of 17 patients with a clinical diagnosis of MSS, conventional sequencing
      of NFIX revealed frameshift and splice-site mutations in 10 individuals. Using
      multiplex ligation-dependent probe amplification analysis, we identified a
      recurrent deletion of NFIX exon 6 and 7 in five individuals. We demonstrate this
      recurrent deletion is the product of a recombination between AluY elements
      located in intron 5 and 7. Two other patients had smaller deletions affecting
      exon 6. These findings show that MSS is a genetically homogeneous Mendelian
      disorder. RT-PCR experiments with newly identified NFIX mutations including the
      recurrent exon 6 and 7 deletion confirmed previous findings indicating that MSS
      associated mutant mRNAs are not cleared by nonsense-mediated mRNA decay.
      Predicted MSS-associated mutant NFIX proteins consistently have a preserved DNA
      binding and dimerization domain, whereas they grossly vary in their C-terminal
      portion. This is in line with the hypothesis that MSS-associated mutations encode
      dysfunctional proteins that act in a dominant negative manner. 

PMID- 24924642
TI  - In response to comments on "screening of major depression in epilepsy: the
      Neurologic Depression Disorders Inventory in Epilepsy-Spanish version
      (Argentina).

PMID- 24924643
TI  - Estimating the diagnostic value of the Neurological Disorders Depression
      Inventory for Epilepsy in different languages.

PMID- 24924644
TI  - Terminology and prognosis of Dravet syndrome.

PMID- 24924645
TI  - In response to terminology and prognosis of Dravet syndrome.

PMID- 24924646
TI  - Thalamotemporal impairment in benign temporal lobe epilepsy: same hypotheses?

PMID- 24924647
TI  - Energized by love: thinking about romantic relationships increases positive
      affect and blood glucose levels.
AB  - We assessed the impact of thinking of a current romantic partner on acute blood
      glucose responses and positive affect over a short period of time. Participants
      in romantic relationships were randomly assigned to reflect on their partner, an
      opposite-sex friend, or their morning routine. Blood glucose levels were assessed
      prior to reflection, as well as at 10 and 25 min postreflection. Results revealed
      that individuals in the routine and friend conditions exhibited a decline in
      glucose over time, whereas individuals in the partner condition did not exhibit
      this decline (rather, a slight increase) in glucose over time. Reported positive
      affect following reflection was positively associated with increases in glucose,
      but only for individuals who reflected on their partner, suggesting this
      physiological response reflects eustress. These findings add to the literature on
      eustress in relationships and have implications for relationship processes.

PMID- 24924648
TI  - Effects of dietary substitution of zinc-methionine for inorganic zinc sources on
      growth performance, tissue zinc accumulation and some blood parameters in broiler
      chicks.
AB  - This study was designed to evaluate the effects of dietary inclusion of zinc
      methionine (ZnMet) as a replacement for conventional inorganic zinc sources on
      performance, tissue zinc accumulation and some plasma indices in broiler chicks.
      A total of 450-day-old Ross male broiler chicks were randomly assigned to five
      pen replicates of nine experimental diets. Dietary treatments consisted of two
      basal diets supplemented with 40 mg/kg added Zn as feed-grade Zn sulphate or Zn
      oxide in which, Zn was replaced with that supplied from ZnMet complex by 25, 50,
      75 or 100%. At 42 days of age, three randomly selected birds from each pen were
      bled to measure plasma metabolites; then, the chicks were slaughtered to evaluate
      carcass characteristics. Results showed that dietary treatments affected (p <
      0.05) feed intake during the starter period, and chicks on Zn oxide diets
      consumed more feed than sulphate counterparts. Furthermore, dietary substitution
      of inorganic Zn sources by ZnMet caused improvements (p < 0.01) in body weight
      gain during all experimental periods. Dietary supplementation of ZnMet improved
      feed conversion efficiency during 1-21 and 1-42, but not in 21-42 days of age.
      Complete replacement of inorganic Zn by that supplied from ZnMet caused an
      increase (p < 0.05) in relative liver weight. Similarly, dietary inclusion of
      ZnMet increased breast meat and carcass yields and reduced abdominal fat
      percentage (p < 0.05). Incremental levels of ZnMet increased (p < 0.05) zinc
      concentrations in liver and thymus, and the highest zinc accumulations were seen
      in 100% ZnMet-supplemented birds. Interestingly, introduction of ZnMet into the
      diets partially in place of inorganic sources resulted in decreases (p < 0.01) in
      plasma uric acid and triglycerides concentrations. The present findings indicated
      that dietary ZnMet inclusion in replacement of inorganic sources in addition to
      improving growth performance, reduced plasma uric acid and triglycerides
      concentrations, consequently decreased abdominal fat pad and increased carcass
      meat yield.

PMID- 24924649
TI  - Description of the behavior of praying mantis with particular reference to
      grooming.
AB  - Eighteen behavior patterns, encompassing most of the observable behavior of
      individually housed praying mantids, Sphodromantis lineola, were recorded using a
      point sampling technique. The data were sorted into four major behavioral
      categories: (1) food acquisition, (2) grooming, (3) inactivity, and (4)
      locomotion and miscellaneous. The mantids spent most of the time in an inactive
      state, which is consistent with their way of life as ambushing predators. Most of
      the animals' active time was spent in food acquisition (60%). Grooming behaviors
      comprised 16.7% of the active time; foreleg grooming represented 82% of grooming,
      while head grooming represented 14.3%. Analysis of the behavioral states in close
      temporal proximity to head grooming indicated that head grooming often follows
      foreleg grooming, occuring in bouts of about 1/2 to 1 min duration. Foreleg
      grooming is also closely associated with eating and seems to represent a pivotal
      behavior pattern between food acquisition and grooming, possibly sharing causal
      factors with both. 

PMID- 24924650
TI  - Defensive behaviour and its inheritance in the anabantoid fish, Macropodus
      opercularis and Macropodus opercularis concolor.
AB  - In this preliminary study defense behaviour patterns (fear responses) are
      described in two closely related, behaviourally different inbred labyrinth fish
      subspecies and in their F1 generation. The subspecies M. opercularis
      (characterized briefly by "active escape") and M. opercularis concolor
      (characterized by "passive escape") showed specific differences in the
      manifestation of certain defense behaviour patterns. In the F1 hybrid generation
      dominance and overdominance of M. opercularis was found in most defense behaviour
      patterns. Analysing the frequencies and sequences of movement patterns it could
      be shown that defensive behaviour is not a random or entirely "plastic" process
      but that there is sequential linkage between the patterns and they form
      characteristic clusters. Our results suggest that manifestations of different
      patterns are under genetic control and presumably, genetic determination of
      certain patterns is not very complex. Attempts were made to determine whole brain
      noradrenaline, serotonine and dopamine levels of the two subspecies and a
      significant difference was found in the noradrenaline content. 

PMID- 24924651
TI  - Modification of prey-catching behavior by learning in the common toad (Bufo b.
      bufo [L], Anura, Amphibia): Changes in responses to visual objects and effects of
      auditory stimuli.
AB  - An attempt to train common toads (Bufo b. bufo) to make the turning movements
      associated with prey-catching in response to a tone (1000 Hz, 90 dB) was
      unsuccessful. However, some toads learned to discriminate food that had been made
      unpalatable from palatable food of identical appearance, when the former was
      accompanied by the auditory stimulus. By making the prey unpalatable flight
      behavior could be induced in toads presented with a housefly (Musca domestica).
      On the other hand, toads could be trained to exhibit prey-catching behavior when
      shown predator objects 30 cm wide and 60 cm high (at a distance of ca. 50 cm).
      The toads also learned to snap at motionless, unscented food in certain
      surroundings. 

PMID- 24924652
TI  - Behavioural effects of hyperstriatal ablation in Gallus domesticus.
AB  - Hens with bilateral ablations in the hyperstriatal complex were compared with
      birds with bilateral ablations in the posterior telencephalon and sham-operated
      controls with regard to their behaviour in their home pens, exploratory behavior
      and their responses to (1) a simulated aerial predator, (2) a startling stimulus
      and (3) an auditory stimulus. Ablations involving the ventral hyperstriatum made
      the birds less reactive to frightening stimuli while ablations in the posterior
      telencephalon resulted in the bird "freezing" in the experimental situations. 

PMID- 24924653
TI  - Coyote senses in predation: Environmental influences on their relative use.
AB  - The purpose of this study was to determine the relative importance of vision,
      audition, and olfaction to coyotes (Canis latrans) hunting under various
      environmental conditions. The time durations for four coyotes to locate rabbits
      within a large outdoor enclosure were determined, with the visual, auditory, and
      olfactory stimuli emitted by the rabbits blocked individually, in pairs, and
      altogether. Visual stimuli were eliminated by conducting the tests only during
      sub-threshold nocturnal conditions. Auditory stimuli were eliminated by killing
      the rabbits immediately prior to a test. Olfactory stimuli were eliminated by
      inducing anosmia in each coyote through irrigation of the nasal mucosa with a 10%
      zinc sulphate solution. The relative importance of these three senses in
      decreasing order was concluded to be: vision, olfaction, and audition. 

PMID- 24924654
TI  - Adults' responses to infants varying in perceived cuteness.
AB  - The effects of perceived cuteness of infant photographs on the behaviour of young
      adults was investigated. Looking, facial muscle activity, and skin conductance
      were measured during individual presentations of the photographs, whereas only
      looking was measured during paired presentations. Both measures of looking time
      were significantly affected by the perceived cuteness of infant photographs, with
      infants ranked as most cute looked at longest and those ranked least cute looked
      at for the shortest length of time. Increased facial muscle activity previously
      associated with pleasant or happy facial expressions was associated with
      presentations of infant photographs but was not related to perceived cuteness. A
      second experiment indicated that increased facial muscle activity was specific to
      infant photographs. Adult responses to infant physical appearance appear to be
      regulated by two mechanisms: an initial positive response to "babyishness",
      reflected by increased facial zygomaticus muscle activity, and an individual
      cognitive preference response to "cuteness", reflected by differential looking
      times. 

PMID- 24924655
TI  - Comparative ethometrics: Congruence of different multivariate analyses applied to
      the same ethological data.
AB  - Five statistically appropriate multivariate analyses were applied to the same
      data on burrowing in the sea hare Aplysia brasiliana to: (1) identify homogeneous
      subject-related subgroups within a heterogeneous sample, and (2) compare the
      extent of congruency among the analyses in terms of the number of extracted
      subgroups and each subject's placement within the subgroups. Raw scores from 32
      subjects on ten burrowing parameters were origin-corrected, standardized to z
      scores, and normalized in order to facilitate comparisons among the analyses. One
      to five identified subgroups were extracted which indicated sensitivity
      differences to sampling variability among the methods. These results suggested
      that selecting a biologically interpretable analysis represents the subjective
      aspect of quantitative data treatment. Q-factor analysis (three subgroups) and
      linear typal analysis (four subgroups) yielded the most biologically
      interpretable subgroups for these data. Multidimensional scaling (one group) and
      principal-components analysis (two subgroups) tended to "lump" subjects, while
      simple distance-function cluster analysis (five subgroups) tended to "split"
      subjects into additional groups. As a diagonistic tool, multivariate analyses
      provide insight into underlying dimensions of individual variation and help
      generate testable hypotheses for guiding future research. 

PMID- 24924657
TI  - The association between sleep characteristics and prothrombotic markers in a
      population-based sample: Chicago Area Sleep Study.
AB  - BACKGROUND AND AIM: Short sleep duration and poor quality sleep are associated
      with coronary heart disease (CHD) mortality; however, the underlying
      pathophysiologic process remains unclear. Sleep apnea may confound the
      association because of its relationship with formation of thrombi, the vascular
      occlusive process in CHD. We tested whether sleep duration and quality were
      associated with prothrombotic biomarkers in adults with a low probability of
      apnea. METHODS: We included adults aged 35-64 years recruited from the community
      and who had an apnea hypopnea index <15 after one night of screening (n=506).
      Sleep duration and maintenance were determined from 7 days of wrist actigraphy;
      daytime sleepiness was estimated using the Epworth Sleepiness Scale. Factor VIII
      (FVIII), von Willebrand factor (vWF), thrombin antithrombin (TAT) complexes, and
      plasminogen activator inhibitor-1 (PAI-1) were measured in fasting blood.
      RESULTS: Sleep duration, maintenance, and daytime sleepiness were not associated
      with FVIII, vWf, or TAT. Sleep maintenance was modestly inversely associated with
      higher levels of log-transformed PAI-1 (beta = -0.07, standard error (SE)=0.03
      per 4.8%, p=0.04) following adjustment for demographic characteristics,
      cardiovascular risk factors, and body mass index (BMI). CONCLUSIONS: Mild
      impairment in sleep was modestly associated with activation of coagulation;
      further study is needed to evaluate the role of fibrinolytic factors in sleep
      mediated coronary thrombosis.

PMID- 24924658
TI  - Management of advanced NK/T-cell lymphoma.
AB  - NK/T-cell lymphomas are aggressive malignancies, and the outlook is poor when
      conventional anthracycline-containing regimens designed for B-cell lymphomas are
      used. With the advent of L-asparaginase-containing regimens, treatment outcome
      has significantly improved. L-asparaginase-containing regimens are now considered
      the standard in the management of NK/T-cell lymphomas. In advanced diseases,
      however, outcome remains unsatisfactory, with durable remission achieved in only
      about 50% of cases. Stratification of patients with advanced NK/T-cell lymphomas
      is needed, so that poor-risk patients can be given additional therapy to improve
      outcome. Conventional presentation parameters are untested and appear inadequate
      for prognostication when L-asparaginase-containing regimens are used. Recent
      evidence suggests that dynamic factors during treatment and interim assessment,
      including Epstein-Barr virus (EBV) DNA quantification and positron emission
      tomography computed tomography findings, are more useful in patient
      stratification. The role of high-dose chemotherapy and haematopoietic stem cell
      transplantation requires evaluation in an overall risk-adapted treatment
      algorithm.

PMID- 24924659
TI  - Insights from a pilot program to integrate medical and social services.
AB  - This study examines lessons learned from the design, implementation, and early
      results of an integrated managed care pilot program linking member benefits of a
      Medicare-Medicaid health care plan with community services and supports. The
      health plan's average monthly costs for members receiving an assessment and
      services declined by an economically meaningful, statistically significant amount
      in the postintervention period relative to the preintervention period compared
      with those who did not accept an assessment or services. The results along with
      the lesson learned from the pilot are viewed by the parties as supportive of
      further program development. 

PMID- 24924660
TI  - Fate and effects of poly- and perfluoroalkyl substances in the aquatic
      environment: a review.
AB  - Polyfluoroalkyl and perfluoroalkyl substances (PFASs) are distributed
      ubiquitously in the aquatic environment, which raises concern for the flora and
      fauna in hydrosystems. The present critical review focuses on the fate and
      adverse effects of PFASs in the aquatic environment. The PFASs are continuously
      emitted into the environment from point and nonpoint sources such as sewage
      treatment plants and atmospheric deposition, respectively. Although
      concentrations of single substances may be too low to cause adverse effects,
      their mixtures can be of significant environmental concern. The production of C8 
      based PFASs (i.e., perfluorooctane sulfonate [PFOS] and perfluorooctanoate
      [PFOA]) is largely phased out; however, the emissions of other PFASs, in
      particular short-chain PFASs and PFAS precursors, are increasing. The PFAS
      precursors can finally degrade to persistent degradation products, which are, in
      particular, perfluoroalkane sulfonates (PFSAs) and perfluoroalkyl carboxylates
      (PFCAs). In the environment, PFSAs and PFCAs are subject to partitioning
      processes, whereby short-chain PFSAs and PFCAs are mainly distributed in the
      water phase, whereas long-chain PFSAs and PFCAs tend to bind to particles and
      have a substantial bioaccumulation potential. However, there are fundamental
      knowledge gaps about the interactive toxicity of PFAS precursors and their
      persistent degradation products but also interactions with other natural and
      anthropogenic stressors. Moreover, because of the continuous emission of PFASs,
      further information about their ecotoxicological potential among multiple
      generations, species interactions, and mixture toxicity seems fundamental to
      reliably assess the risks for PFASs to affect ecosystem structure and function in
      the aquatic environment.

PMID- 24924661
TI  - Association between leaflet fusion pattern and thoracic aorta morphology in
      patients with bicuspid aortic valve.
AB  - PURPOSE: To determine if patients with certain bicuspid aortic valve (BAV)
      phenotypes are predisposed to particular morphological abnormalities of the
      thoracic aorta. MATERIALS AND METHODS: One hundred ninety-two patients with BAV
      who underwent magnetic resonance angiography between January 2007 and July 2010
      were retrospectively identified. Aortic morphology was examined through
      measurements of aortic size index at nine levels along the thoracic aorta, three
      dimensional volume of the ascending aorta, vessel asymmetry, and assessment of
      aortic root morphology. RESULTS: We found 140 patients (73%) with right and left
      coronary cusps (R-L) fusion, 46 patients (24%) with R-N fusion, and 6 patients
      (3%) with left and noncoronary cusps (L-N) fusion. Mean aortic volume in the
      proximal ascending aorta was significantly greater in R-L patients (0.93 versus
      0.60 cm(3)/m(2); P < 0.01). R-N patients possessed greater aortic size index at
      the distal ascending aorta and proximal aortic arch, and were also significantly
      more likely to have Type 2 patterns of aortic dilatation. CONCLUSION: Our results
      suggest that BAV with R-L fusion is associated with increased dimensions of the
      aortic root, while BAV with R-N fusion is associated with increased dimensions of
      the distal ascending aorta and proximal arch. Our findings illustrate the
      morphological heterogeneity that exists among BAV phenotypes.

PMID- 24924662
TI  - Current antimicrobial susceptibility of first-episode melioidosis Burkholderia
      pseudomallei isolates from the Northern Territory, Australia.
AB  - Burkholderia pseudomallei is a saprophytic Gram-negative bacterium responsible
      for the tropical infectious disease melioidosis. Melioidosis is endemic to
      northern Australia and Southeast Asia. In this study, 234 isolates of B.
      pseudomallei obtained from the first positive clinical specimen from 234
      consecutive patients diagnosed with melioidosis between October 2009 and
      September 2012 were reviewed. All isolates were susceptible to meropenem and
      ceftazidime. In total, 226 isolates (96.6%) were susceptible to doxycycline and
      232 (99.1%) were susceptible to trimethoprim/sulfamethoxazole (TMP/SMX; co
      trimoxazole). Primary resistance of B. pseudomallei to ceftazidime and/or
      meropenem is exceedingly rare and clinicians can be confident in the current
      treatment guidelines for melioidosis. Whether the very low rates of TMP/SMX
      resistance seen in Australia reflect the global situation requires further
      studies using Etest, especially to clarify the rate of resistance in Thailand. 

PMID- 24924663
TI  - Alzheimer's Disease prevalence, costs, and prevention for military personnel and
      veterans.
AB  - By 2050, more than 13 million Americans of all ages are estimated to be living
      with Alzheimer's disease (AD), and the aggregate costs of care will swell to
      approximately $1.2 trillion. The rapidly climbing number of those affected with
      AD includes a growing population of aging military veterans affected who may have
      an added risk for the disease as a consequence of traumatic brain injury,
      posttraumatic stress disorder, and/or service-related injuries. The increasing
      number of individuals, the long duration of disability, and the rising cost of
      care for AD and other dementia to our society are important public health
      challenges facing many older adults. These challenges are further compounded by a
      burgeoning military veteran population that is much younger, with an increased
      risk of AD and other dementia, and who may experience decades-long periods of
      disability and care. This outlook underscores the critical need for investments
      in research at the federal and international levels to accelerate the pace of
      progress in developing breakthrough discoveries that will change the trajectory
      of AD and related dementia. 

PMID- 24924664
TI  - Lifestyle and health-related risk factors and risk of cognitive aging among older
      veterans.
AB  - Lifestyle and health-related factors are critical components of the risk for
      cognitive aging among veterans. Because dementia has a prolonged prodromal phase,
      understanding effects across the life course could help focus the timing and
      duration of prevention targets. This perspective may be especially relevant for
      veterans and health behaviors. Military service may promote development and
      maintenance of healthy lifestyle behaviors, but the period directly after active
      duty has ended could be an important transition stage and opportunity to address
      some important risk factors. Targeting multiple pathways in one intervention may
      maximize efficiency and benefits for veterans. A recent review of modifiable risk
      factors for Alzheimer's disease estimated that a 25% reduction of a combination
      of seven modifiable risk factors including diabetes, hypertension, obesity,
      depression, physical inactivity, smoking, and education/cognitive inactivity
      could prevent up to 3 million cases worldwide and 492,000 cases in the United
      States. Lifestyle interventions to address cardiovascular health in veterans may
      serve as useful models with both physical and cognitive activity components,
      dietary intervention, and vascular risk factor management. Although the evidence
      is accumulating for lifestyle and health-related risk factors as well as military
      risk factors, more studies are needed to characterize these factors in veterans
      and to examine the potential interactions between them. 

PMID- 24924667
TI  - Stress, PTSD, and dementia.
AB  - The physiological consequences of acute and chronic stress on a range of organ
      systems have been well documented after the pioneering work of Hans Selye more
      than 70 years ago. More recently, an association between exposure to stressful
      life events and the development of later-life cognitive dysfunction has been
      proposed. Several plausible neurohormonal pathways and genetic mechanisms exist
      to support such an association. However, many logistical and methodological
      barriers must be overcome before a defined causal linkage can be firmly
      established. Here the authors review recent studies of the long-term cognitive
      consequences of exposures to cumulative ordinary life stressors as well as
      extraordinary traumatic events leading to posttraumatic stress disorder.
      Suggestive effects have been demonstrated for the role of life stress in general,
      and posttraumatic stress disorder in particular, on a range of negative cognitive
      outcomes, including worse than normal changes with aging, Alzheimer's disease,
      and vascular dementia. However, given the magnitude of the issue, well-controlled
      studies are relatively few in number, and the effects they have revealed are
      modest in size. Moreover, the effects have typically only been demonstrated on a
      selective subset of measures and outcomes. Potentially confounding factors abound
      and complicate causal relationships despite efforts to contain them. More well
      controlled, carefully executed longitudinal studies are needed to confirm the
      apparent association between stress and dementia, clarify causal relationships,
      develop reliable antemortem markers, and delineate distinct patterns of risk in
      subsets of individuals.

PMID- 24924666
TI  - Are hippocampal size differences in posttraumatic stress disorder mediated by
      sleep pathology?
AB  - Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the
      hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic
      relationships are reviewed briefly, including the hypothesis that sleep
      disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this
      includes findings that insomnia and restricted sleep are associated with changes
      in hippocampal cell regulation and impairments in cognition. We present results
      of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated
      with lower hippocampal volume. We outline a broad research agenda centered on the
      hypothesis that sleep changes mediate the relationship between PTSD and
      hippocampal volume. 

PMID- 24924668
TI  - Depression and dementias among military veterans.
AB  - Depression is very common throughout the course of veterans' lives, and dementia
      is common in late life. Previous studies suggest an association between
      depression and dementia in military veterans. The most likely biologic mechanisms
      that may link depression and dementia among military veterans include vascular
      disease, changes in glucocorticoid steroids and hippocampal atrophy, deposition
      of beta-amyloid plaques, inflammatory changes, and alterations of nerve growth
      factors. In addition, military veterans often have depression comorbid with
      posttraumatic stress disorder or traumatic brain injury. Therefore, in military
      veterans, these hypothesized biologic pathways going from depression to dementia
      are more than likely influenced by trauma-related processes. Treatment strategies
      for depression, posttraumatic stress disorder, or traumatic brain injury could
      alter these pathways and as a result decrease the risk for dementia. Given the
      projected increase of dementia, as well as the projected increase in the older
      segment of the veteran population, in the future, it is critically important that
      we understand whether treatment for depression alone or combined with other
      regimens improves cognition. In this review, we summarize the principal
      mechanisms of this relationship and discuss treatment implications in military
      veterans. 

PMID- 24924669
TI  - Cognitive changes and dementia risk after traumatic brain injury: implications
      for aging military personnel.
AB  - Traumatic brain injury (TBI) is recognized as an important risk factor for the
      long-term cognitive health of military personnel, particularly in light of
      growing evidence that TBI increases risk for Alzheimer's disease and other
      dementias. In this article, we review the neurocognitive and neuropathologic
      changes after TBI with particular focus on the potential risk for cognitive
      decline across the life span in military service members. Implications for
      monitoring and surveillance of cognition in the aging military population are
      discussed. Additional studies are needed to clarify the factors that increase
      risk for later life cognitive decline, define the mechanistic link between these
      factors and dementia, and provide empirically supported interventions to mitigate
      the impact of TBI on cognition across the life span. 

PMID- 24924665
TI  - Smoking and increased Alzheimer's disease risk: a review of potential mechanisms.
AB  - BACKGROUND: Cigarette smoking has been linked with both increased and decreased
      risk for Alzheimer's disease (AD). This is relevant for the US military because
      the prevalence of smoking in the military is approximately 11% higher than in
      civilians. METHODS: A systematic review of published studies on the association
      between smoking and increased risk for AD and preclinical and human literature on
      the relationships between smoking, nicotine exposure, and AD-related
      neuropathology was conducted. Original data from comparisons of smoking and never
      smoking cognitively normal elders on in vivo amyloid imaging are also presented.
      RESULTS: Overall, literature indicates that former/active smoking is related to a
      significantly increased risk for AD. Cigarette smoke/smoking is associated with
      AD neuropathology in preclinical models and humans. Smoking-related cerebral
      oxidative stress is a potential mechanism promoting AD pathology and increased
      risk for AD. CONCLUSIONS: A reduction in the incidence of smoking will likely
      reduce the future prevalence of AD.

PMID- 24924671
TI  - The critical need for defining preclinical biomarkers in Alzheimer's disease.
AB  - The increasing number of afflicted individuals with late-onset Alzheimer's
      disease (AD) poses significant emotional and financial burden on the world's
      population. Therapeutics designed to treat symptoms or alter the disease course
      have failed to make an impact, despite substantial investments by governments,
      pharmaceutical industry, and private donors. These failures in treatment efficacy
      have led many to believe that symptomatic disease, including both mild cognitive
      impairment (MCI) and AD, may be refractory to therapeutic intervention. The
      recent focus on biomarkers for defining the preclinical state of MCI/AD is in the
      hope of defining a therapeutic window in which the neural substrate remains
      responsive to treatment. The ability of biomarkers to adequately define the at
      risk state may ultimately allow novel or repurposed therapeutic agents to finally
      achieve the disease-modifying status for AD. In this review, we examine current
      preclinical AD biomarkers and suggest how to generalize their use going forward. 

PMID- 24924670
TI  - Imaging chronic traumatic brain injury as a risk factor for neurodegeneration.
AB  - Population-based studies have supported the hypothesis that a positive history of
      traumatic brain injury (TBI) is associated with an increased incidence of
      neurological disease and psychiatric comorbidities, including chronic traumatic
      encephalopathy, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral
      sclerosis. These epidemiologic studies, however, do not offer a clear definition
      of that risk, and leave unanswered the bounding criteria for greater lifetime
      risk of neurodegeneration. Key factors that likely mediate the degree of risk of
      neurodegeneration include genetic factors, significant premorbid and comorbid
      medical history (e.g. depression, multiple head injuries and repetitive
      subconcussive impact to the brain, occupational risk, age at injury, and severity
      of brain injury). However, given the often-described concerns in self-report
      accuracy as it relates to history of multiple TBIs, low frequency of patient
      presentation to a physician in the case of mild brain injuries, and challenges
      with creating clear distinctions between injury severities, disentangling the
      true risk for neurodegeneration based solely on population-based studies will
      likely remain elusive. Given this reality, multiple modalities and approaches
      must be combined to characterize who are at risk so that appropriate
      interventions to alter progression of neurodegeneration can be evaluated. This
      article presents data from a study that highlights uses of neuroimaging and areas
      of needed research in the link between TBI and neurodegenerative disease. 

PMID- 24924672
TI  - The disease intersection of susceptibility and exposure: chemical exposures and
      neurodegenerative disease risk.
AB  - Alzheimer's disease, Parkinson's disease, and motor neuron disease, the most
      common of the late-life neurodegenerative disorders, are in most cases thought to
      have complex etiologies. Common features among these disorders include insidious
      onset, pathological findings of protein aggregates and selected neuronal
      degeneration, and resulting characteristic clinical syndromes. The number of
      elders in the United States, including aging veterans, is increasing.
      Investigation of causes and preventive interventions for neurodegenerative
      disorders is increasingly relevant. Recent epidemiological and laboratory studies
      suggest that exposures years or decades before diagnosis can trigger the
      processes that ultimately result in a neurodegenerative disease. If this is
      correct, preventive measures may be needed in midlife or earlier. This article
      will focus on putative risk factors relevant to military service. 

PMID- 24924674
TI  - Prisoner of war status, posttraumatic stress disorder, and dementia in older
      veterans.
AB  - BACKGROUND: It is not known whether prisoners of war (POWs) are more likely to
      develop dementia independently of the effects of posttraumatic stress disorder
      (PTSD). METHODS: We performed a retrospective cohort study in 182,879 U.S.
      veterans age 55 years and older, and examined associations between POW status and
      PTSD at baseline (October 1, 2000-September 30, 2003), and incident dementia
      during follow-up (October 1, 2003-September 30, 2012). RESULTS: A total of 484
      veterans (0.3%) reported being POWs, of whom 150 (31.0%) also had PTSD. After
      adjusting for demographics, medical and psychiatric comorbidities, period of
      service, and the competing risk of death, the risk of dementia was increased in
      veterans who were POWs only (hazard ratio [HR], 1.61; 95% confidence interval
      [CI], 1.30-1.98) or had PTSD only (HR, 1.52; 95% CI, 1.41-1.64) and was greatest
      in veterans who were POWs and also had PTSD (HR, 2.24; 95% CI, 1.72-2.92).
      CONCLUSIONS: POW status and PTSD increase risk of dementia in an independent,
      additive manner in older veterans.

PMID- 24924673
TI  - Effects of traumatic brain injury and posttraumatic stress disorder on
      Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging
      Initiative.
AB  - Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are
      common problems resulting from military service, and both have been associated
      with increased risk of cognitive decline and dementia resulting from Alzheimer's
      disease (AD) or other causes. This study aims to use imaging techniques and
      biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD
      resulting from combat or other traumas increase the risk for AD and decrease
      cognitive reserve in Veteran subjects, after accounting for age. Using military
      and Department of Veterans Affairs records, 65 Vietnam War veterans with a
      history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD
      without TBI, and 65 control subjects are being enrolled in this study at 19
      sites. The study aims to select subject groups that are comparable in age,
      gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI)
      or dementia are being excluded. However, a new study just beginning, and similar
      in size, will study subjects with TBI, subjects with PTSD, and control subjects
      with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal
      fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and
      resting state blood-level oxygen dependent (BOLD) functional magnetic resonance
      imaging); and amyloid positron emission tomographic (PET) images with florbetapir
      are being obtained. One-year follow-up measurements will be collected for most of
      the baseline procedures, with the exception of the lumbar puncture, the PET
      imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46
      with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13
      clinics to undergo the study protocol. It is expected that cohorts will be fully
      recruited by October 2014. This study is a first step toward the design and
      statistical powering of an AD prevention trial using at-risk veterans as
      subjects, and provides the basis for a larger, more comprehensive study of
      dementia risk factors in veterans. 

PMID- 24924676
TI  - In vivo tau imaging: obstacles and progress.
AB  - The military conflicts of the last decade have highlighted the growing problem of
      traumatic brain injury in combatants returning from the battlefield. The
      considerable evidence pointing at the accumulation of tau aggregates and its
      recognition as a risk factor in neurodegenerative conditions such as Alzheimer's
      disease have led to a major effort to develop selective tau ligands that would
      allow research into the physiopathologic underpinnings of traumatic brain injury
      and chronic traumatic encephalopathy in military personnel and the civilian
      population. These tracers will allow new insights into tau pathology in the human
      brain, facilitating research into causes, diagnosis, and treatment of traumatic
      encephalopathy and major neurodegenerative dementias, such as Alzheimer's disease
      and some variants of frontotemporal lobar degeneration, in which tau plays a
      role. The field of selective tau imaging has to overcome several obstacles, some
      of them associated with the idiosyncrasies of tau aggregation and others related
      to radiotracer design. A worldwide effort has focused on the development of
      imaging agents that will allow selective tau imaging in vivo. Recent progress in
      the development of these tracers is enabling the noninvasive assessment of the
      extent of tau pathology in the brain, eventually allowing the quantification of
      changes in tau pathology over time and its relation to cognitive performance,
      brain volumetrics, and other biomarkers, as well as assessment of efficacy and
      patient recruitment for antitau therapeutic trials.

PMID- 24924675
TI  - Military-related traumatic brain injury and neurodegeneration.
AB  - Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most
      exposures to explosive blast from improvised explosive devices. mTBI is the most
      common traumatic brain injury affecting military personnel; however, it is the
      most difficult to diagnose and the least well understood. It is also recognized
      that some mTBIs have persistent, and sometimes progressive, long-term
      debilitating effects. Increasing evidence suggests that a single traumatic brain
      injury can produce long-term gray and white matter atrophy, precipitate or
      accelerate age-related neurodegeneration, and increase the risk of developing
      Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition,
      repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic
      encephalopathy. We found early changes of chronic traumatic encephalopathy in
      four young veterans of the Iraq and Afghanistan conflict who were exposed to
      explosive blast and in another young veteran who was repetitively concussed. Four
      of the five veterans with early-stage chronic traumatic encephalopathy were also
      diagnosed with posttraumatic stress disorder. Advanced chronic traumatic
      encephalopathy has been found in veterans who experienced repetitive neurotrauma
      while in service and in others who were accomplished athletes. Clinically,
      chronic traumatic encephalopathy is associated with behavioral changes, executive
      dysfunction, memory loss, and cognitive impairments that begin insidiously and
      progress slowly over decades. Pathologically, chronic traumatic encephalopathy
      produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus;
      septal abnormalities; and abnormal deposits of hyperphosphorylated tau as
      neurofibrillary tangles and disordered neurites throughout the brain. The
      incidence and prevalence of chronic traumatic encephalopathy and the genetic risk
      factors critical to its development are currently unknown. Chronic traumatic
      encephalopathy has clinical and pathological features that overlap with
      postconcussion syndrome and posttraumatic stress disorder, suggesting that the
      three disorders might share some biological underpinnings. 

PMID- 24924677
TI  - Military risk factors for Alzheimer's dementia and neurodegenerative disease.

PMID- 24924678
TI  - Military Risk Supplement. Preface.

PMID- 24924679
TI  - Introduction: Evolution of military and veterans brain health research.

PMID- 24924680
TI  - Military traumatic brain injury: a review.
AB  - Military mild traumatic brain injury (mTBI) differs from civilian injury in
      important ways. Although mTBI sustained in both military and civilian settings
      are likely to be underreported, the combat theater presents additional obstacles
      to reporting and accessing care. The impact of blast forces on the nervous system
      may differ from nonblast mechanisms, mTBI although studies comparing the
      neurologic and cognitive sequelae in mTBI survivors have not provided such
      evidence. However, emotional distress appears to figure prominently in symptoms
      following military mTBI. This review evaluates the extant literature with an eye
      towards future research directions. 

PMID- 24924681
TI  - Common use of prescription off-label acne therapy in children younger than 12
      years old.
AB  - Acne is occurring more frequently in younger age groups, but most available
      treatments are considered off-label in young children. As the epidemiology of
      acne has changed to include younger children over the past 20 years, neither
      regulators, pharmaceutical companies, nor clinicians have understood the need or
      value of obtaining regulatory sanctions for problems physicians have managed
      using clinical judgment. The objective of this study was to analyze the frequency
      of off-label acne treatment according to age and other demographic factors. We
      searched the National Ambulatory Medical Care Survey from 1993 to 2010 for visits
      in children younger than 12 years of age for the diagnosis of International
      Classification of Diseases, Ninth Revision, code 706.1. We tabulated leading acne
      treatments and assessed factors associated with off-label prescribing. Off-label
      but appropriate acne treatments were used in 29% of acne visits for children
      younger than 12 years of age. Dermatologists were more likely than pediatricians
      to prescribe off-label treatment (p < 0.001). The most frequently used off-label
      treatments were topical retinoids, followed by oral antibiotics. There was no
      significant trend in the rate of off-label prescribing over time (p = 0.40). Off
      label treatment is well within the standard of care for young children with acne.
      More data on the use of topical retinoids in young children will improve our
      understanding of their use, which may help optimize treatment outcomes for
      children with acne.

PMID- 24924682
TI  - Implementing drug safety updates.

PMID- 24924683
TI  - Prescribing drugs for Alzheimer's disease in primary care: managing cognitive
      symptoms.
AB  - There are currently no interventions that cure or even alter the progressive
      course of dementia. In the UK, donepezil, galantamine and rivastigmine are
      licensed for symptomatic treatment of mild to moderate Alzheimer's disease, and
      memantine is licensed for use in moderate to severe Alzheimer's disease.1-4 These
      drugs improve cognitive function by a modest amount compared with placebo.5
      Although the National Institute for Health and Care Excellence (NICE) stipulates
      that such treatment should be initiated by a specialist, in many parts of the UK
      responsibility for continued prescription of these drugs is being transferred to
      primary care. Here we review the evidence for drugs prescribed for cognitive
      symptoms in Alzheimer's disease and highlight key issues for those who are
      prescribing them. 

PMID- 24924684
TI  - Ten Important Elements for Observational Studies in Primary Care and Community
      Health.

PMID- 24924685
TI  - Histogram and vertical bar diagram: often misapprehended concept.

PMID- 24924686
TI  - Answer to: "Histogram and vertical bar diagram: often misapprehended concept" by
      M. Lakshmanan.

PMID- 24924687
TI  - MiR-132 inhibits expression of SIRT1 and induces pro-inflammatory processes of
      vascular endothelial inflammation through blockade of the SREBP-1c metabolic
      pathway.
AB  - PURPOSE: Inflammation participates centrally in all stages of atherosclerosis
      (AS), which begins with pro-inflammatory processes and inflammatory changes in
      the endothelium, related to lipid metabolism. MicroRNA (miRNA) inhibition of
      inflammation related to SIRT1 has been shown to be a promising therapeutic
      approach for AS. However, the mechanism of action is unknown. METHODS: We
      investigated whether miRNAs regulate the SIRT1 and its downstream SREBP
      lipogenesis-cholesterogenesis metabolic pathway in human umbilical vein
      endothelial cells (HUVECs). HUVECs were transfected with miR-132 mimics and
      inhibitors, and then treated with or without tumor necrosis factor alpha
      (TNFalpha). The effects of miR-132 on pro-inflammatory processes, proliferation
      and apoptosis were assessed. RESULTS: We identified that the relative 3' UTR
      luciferase activities of SIRT1 were significantly decreased in miR-132
      transfected HUVECs (0.338 +/- 0.036) compared to control (P = 0.000). miR-132
      inhibited SIRT1 expression of mRNA level in HUVECs (0.53 +/- 0.06) (P < 0.01) as
      well as proteins of SIRT1. mRNA expression and protein levels of SREBP (0.45 +/-
      0.07), fatty acid synthase (FASN) (0.55 +/- 0.09) and 3-hydroxy-3-methylglutaryl
      CoA reductase (HMGCR) (0.62 +/- 0.08) (P < 0.01), which are downstream regulated
      genes, were reduced in HUVECs by miR-132. MiR-132 promoted pro-inflammatory
      processes and apoptosis of HUVECs induced by TNF-alpha, and inhibited its
      proliferation, viability and migration. CONCLUSIONS: SIRT1 mRNAs are direct
      targets of miR-132. miR-132 controls lipogenesis and cholesterogenesis in HUVECs
      by inhibiting SIRT1 and SREBP-1c expression and their downstream regulated genes,
      including FASN and HMGCR. Inhibition of SIRT1 by miR-132 was associated with
      lipid metabolism-dependent pro-inflammatory processes in HUVECs. The newly
      identified miRNA, miR-132 represents a novel targeting mechanism for AS therapy.

PMID- 24924688
TI  - Ultrasound-guided lateral infraclavicular block evaluated by infrared
      thermography and distal skin temperature.
AB  - BACKGROUND: Brachial plexus blocks cause changes in hand and digit skin
      temperature. We investigated thermographic patterns after the lateral
      infraclavicular brachial plexus block. We hypothesised that a successful lateral
      infraclavicular block could be predicted by increased skin temperature of the 2nd
      and 5th digits. METHODS: We performed an ultrasound-guided lateral
      infraclavicular block in 45 patients undergoing upper limb surgery. The
      contralateral hand served as control and we obtained infrared thermographic
      images of both hands before the block and during the following 30 min. We defined
      areas of interest on the hands and analysed mean skin temperature of each area.
      RESULTS: Forty patients completed the study. Thirty blocks were successful, six
      were failures and four were partial failures. Four distinct patterns of skin
      temperature changes were revealed with highly significant changes in temperature,
      depending on block success. A simultaneous 1  degrees C ipsilateral increase in
      skin temperature of the 2nd and 5th digits predicted a successful block with a
      positive predictive value of 100%. A 5  degrees C difference in digit skin
      temperature compared with the contralateral hand had a positive predictive value
      of 96%, and a digit skin temperature <= 30  degrees C 30  min after performing
      the block had a predictive value of 100% for a failed block. CONCLUSIONS: Four
      different thermographic patterns were found. Simultaneous increases in skin
      temperature of both the 2nd and 5th digits predicted lateral infraclavicular
      block success with a positive predictive value of 100%. Digit skin temperature <=
      30  degrees C 30 min after performing the block indicated block failure.

PMID- 24924689
TI  - Change in texture improvement of low-fat tofu by means of low-fat soymilk protein
      denaturation.
AB  - BACKGROUND: Tofu made from low-fat soy flour is a nutritional food for consumers
      and economically benefits the food processor. However, low-fat tofu has poor
      textural quality, especially insufficient firmness. Stepwise heating (heating at
      75  degrees C, followed by holding at 95  degrees C) of full-fat soymilk
      increases gel properties. Therefore we evaluated the two-step heating of low-fat
      soymilk to improve tofu texture. RESULTS: The denaturation enthalpy and
      temperature of beta-conglycinin and glycinin were higher in low-fat tofu compared
      to high-fat tofu. The viscosity of low-fat soymilk and texture of tofu by one
      step heating were weaker than full-fat soymilk and tofu. However, the two-step
      heating increased free sulfhydryl groups and viscosity of low-fat soymilk to a
      value higher or similar to conventional soymilk. The syneresis of low-fat tofu
      was reduced about 30% and hardness was higher (131.0 N) by the two-step process
      compared to one-step heating of full-fat tofu (101.4 N) by the one-step process.
      The microstructure of low-fat tofu became finer, denser and more homogeneous by
      the two-step heat process. CONCLUSION: Low-fat tofu produced by denaturing the
      two major soy proteins separately had improved textural qualities similar to full
      fat tofu as a result of increased hydrophobic interactions between denatured
      protein molecules.

PMID- 24924690
TI  - Social rank and responses to feeding competition in rhesus monkeys.
AB  - A group of rhesus monkeys (Macaca mulatta) living in a large enclosure received
      food which varied in desirability and spatial distribution. Feeding and agonistic
      behaviour of four hierarchical subgroups were analyzed. In general, there was
      less aggression and improved feeding rates with dispersed food than with piled
      food. The behaviour of high-ranking subjects was the most stable: they usually
      ate first, ate most, and showed little agonistic behaviour. The most subordinate
      subjects were also involved in few agonistic episodes, since they tended to
      remain on the periphery and eat little. However, subordinates obtained access
      earlier to a pile of the most highly prized food (banana pieces) than to piles of
      less attractive foods. Subordinates also obtained their highest feeding score
      when banana pieces were dispersed. This latter condition was associated with
      increased aggression. The feeding behaviour of intermediate-ranking subjects lay
      between that of dominants and subordinates, and the former were involved in more
      aggression. Behaviour in situations involving restricted food reflects cognitive
      processes in which several factors including attractiveness of the food, social
      status, and risks involved are evaluated. 

PMID- 24924691
TI  - Operant conditioning in the newly hatched quail : Fixed interval performance.
AB  - Newly hatched quails and adult controls of the species Coturnix coturnix japonica
      were trained to emit a treadle-pressing response reinforced with food on a Fixed
      Interval 60 seconds schedule, at a pace of 4 or 5 sessions a day. The young
      subjects were successfully shaped at the fourth day of life. Although response
      rates were equivalent in young and adults, Curvature Index values and post
      reinforcement pause durations were higher for the adult subjects over a 10-day
      conditioning period. These differences in the temporal regulation of behavior are
      discussed in relationship with factors involved in developmental studies. 

PMID- 24924692
TI  - [Not Available].
AB  - We have studied feeding and social behaviours in 7 captive wild boars before and
      after farrowing and their early development. The individual feeding strategies
      are varying between two types : "Feeding at the feeders" and "Rooting". Most of
      the individuals (5) are changing their feeding strategy in the second period,
      after farrowing. The social interactions in the group are also changed after
      farrowing ; thus in the second period, females with youngs reduced their
      agonistic interactions, established affiliated relationships and keep away from
      the rest of the group. The frequency of approach of the feeders is positively
      correlated to the degree of affinity and not to the dominance hierarchy.
      Furthermore, the correlation between the feeding strategy and the individual
      social status is positive only before farrowing : the social capacity of
      affiliated behaviour units and the polarity of agonistic interactions is linked
      to the strategy "Feeding at the feeders". From the third week of age, different
      individual feeding and social behaviours are appearing : the youngs develop the
      same types of strategy as their genetic or adoptive mother. Then it appears a
      relation between the social status of the mothers and the feeding strategies of
      the youngs. 

PMID- 24924693
TI  - Changes in male odours and urinary marking patterns due to inhibition of
      aggression in male mice.
AB  - The effects of active inhibition of aggression on male odours and urinary marking
      patterns were studied in mice belonging to a highly aggressive strain the TA
      (Turku Aggressive), which has been developed by selective breeding through 37
      generations. These males were defeated by trained fighters until they showed no
      aggression. Individually housed TA males served as controls. Mice from the
      parental or Normal Strain, which is intermediate in aggression, were exposed to
      the odours. The males from the Normal Strain were tested for aggression against
      male castrates to which urine from the two types of TA males or water had been
      applied. The urine from the highly aggressive control TA males evoked most
      aggression. The Normal males were later tested against castrates on soiled
      sawdust. Fewer attacks occured on sawdust soiled by the urine from the control TA
      males. The preferences for areas covered with soiled sawdust were also assessed.
      The males from the Normal Strain preferred areas soiled by the TA males trained
      to nonaggressiveness while the females preferred areas soiled by the highly
      aggressive control TA males. Subsequently the size and number of urinary marks
      deposited were examined. The TA males trained to nonaggressiveness voided urine
      in fewer but larger pools. The differences showed the same direction as those
      previously found between the TA and TNA strains, selectively bred for aggression
      and non-aggression, respectively. In mice the odour signals and urinary marking
      patterns seem to be correlated with the level of aggressiveness, either
      hereditarily determined or acquired through learning. 

PMID- 24924694
TI  - Imprinting on prey odours in ferrets (Mustela Putorius F. Furo L. ) and its
      neural correlates.
AB  - The effect of different feeding conditions during ontogeny was investigated in
      the carnivorous ferret. Behavioral tests and cardiac responses towards known and
      unknown odours as well as food choice tests showed that in this species olfaction
      plays an important role for prey recognition. Yet, the knowledge of the prey
      odours has to be learned during a sensitive phase which was found to exist
      between postnatal days 60 and 90. In adult ferrets, searching for prey can be
      elicited reliably by familiar odours, unknown odours are not reacted to. The
      maturation of the granule cells of the ferret olfactory bulb around the time of
      prey odour imprinting has been analysed. Rapid Golgi impregnation studies reveal
      a temporal overshoot in the development of the spines on the external dendrites
      of the granule cells. Electron microscopical examinations of the synaptic
      contacts in the external plexiform layer indicate that the time course of synapse
      and reciprocal synapse formation is similar to that of the formation of the
      spines on the external dendrites. The results show that the maturation of the
      external plexiform layer with respect to the number of dentritic spines and
      synapses, occurs at a time when the animal is most sensitive to olfactory
      imprinting stimuli. 

PMID- 24924695
TI  - Is there "pain" in Invertebrates?
AB  - In contrast to nociception, the perception of pain, or pain experience, remains a
      subjective notion applicable to humans, but untestable with animals. Yet, when
      defined operationally as a physiological response induced in an animal by stimuli
      painful to humans, and resulting in a protective stimulus avoidance response,
      pain is amenable to testing with non-human subjects. This paper considers a
      series of examples showing responses to stimuli that are both painful
      (nociceptive) and responsible for eliciting natural self-preserving behavior in
      Invertebrates. Consideration is also given to the evolution and possible
      mechanism underlying the "pain-system" in Invertebrates. 

PMID- 24924696
TI  - Development and psychometric evaluation of the Premarital Sexual Behavior
      Assessment Scale for Young Women (PSAS-YW): an exploratory mixed method study.
AB  - BACKGROUND: Premarital sexual behaviors are important issue for women's health.
      The present study was designed to develop and examine the psychometric properties
      of a scale in order to identify young women who are at greater risk of premarital
      sexual behavior. METHOD: This was an exploratory mixed method investigation.
      Indeed, the study was conducted in two phases. In the first phase, qualitative
      methods (focus group discussion and individual interview) were applied to
      generate items and develop the questionnaire. In the second phase, psychometric
      properties (validity and reliability) of the questionnaire were assessed.
      RESULTS: In the first phase an item pool containing 53 statements related to
      premarital sexual behavior was generated. In the second phase item reduction was
      applied and the final version of the questionnaire containing 26 items was
      developed. The psychometric properties of this final version were assessed and
      the results showed that the instrument has a good structure, and reliability. The
      results from exploratory factory analysis indicated a 5-factor solution for the
      instrument that jointly accounted for the 57.4% of variance observed. The
      Cronbach's alpha coefficient for the instrument was found to be 0.87. CONCLUSION:
      This study provided a valid and reliable scale to identify premarital sexual
      behavior in young women. Assessment of premarital sexual behavior might help to
      improve women's sexual abstinence.

PMID- 24924698
TI  - Parasite control practices on pasture-based dairy farms in the Republic of
      Ireland.
AB  - Dictyocaulus viviparus, Ostertagia ostertagi (nematode parasites), and Fasciola
      hepatica (trematode parasite) result in productivity losses on dairy farms and
      impact on animal health through clinical and sub-clinical disease. Parasite
      control in livestock systems is largely based on the use of chemoprophylactic
      agents (anthelmintics), grazing management, or a combination of both. The
      objective of this study was to document current parasite control measures
      employed by Irish dairy farmers in a predominantly pasture-based livestock
      system. A questionnaire survey of 312 geographically representative farmers was
      completed in 2009 with a follow up survey completed in 2011. Statistical analysis
      highlighted significant differences in chemoprophylactic usage between 2009 and
      2011. In particular, an increase in the use of albendazole for both trematode
      (19% in 2009 to 36% in 2011) and nematode (30% in 2009 to 58% in 2011) control
      was observed. This was most likely due to flukicide restrictions introduced in
      the Republic of Ireland in 2010 for dairy animals. Logistic regression
      highlighted regional differences in chemoprophylactic use. Farmers in southern
      parts of Ireland, an area with good quality soil, less rainfall, and a higher
      density of dairy farms than other regions, were approximately half as likely to
      dose for F. hepatica and were more likely (OR>2.0) to use albendazole for both
      nematode and fluke control. Approximately 30% of respondents who used a
      chemoprophylactic treatment for nematodes, used a product which was 'unsuitable
      for purpose' (e.g. ivermectin for the treatment of F. hepatica), highlighting the
      need for increased awareness, continuing research, and regionally targeted
      education tools regarding optimal parasite control. 

PMID- 24924697
TI  - The addition of C-reactive protein to validated staging systems improves their
      prognostic ability in patients with hepatocellular carcinoma.
AB  - OBJECTIVES: C-reactive protein (CRP) is a practical prognostic marker in patients
      with hepatocellular carcinoma (HCC). We investigated the prognostic value of
      adding the CRP level to other validated staging systems (Cancer Liver Italian
      Program, Japan Integrated Staging, Barcelona Clinic Liver Cancer classification
      system, Tokyo score and tumor node metastasis classification) in HCC patients.
      METHODS: One hundred and eighty-six newly diagnosed HCC patients were
      retrospectively evaluated. A multivariate analysis identified the
      clinicopathological variables associated with overall survival; the variables
      identified were then added to each staging system and compared to those without
      the additional variable. RESULTS: In multivariate analysis, an elevated serum CRP
      level was independently associated with a poor prognosis (hazard ratio 3.792, p <
      0.0001). The addition of the CRP level to each of the established staging systems
      provided a higher linear chi(2) value and a lower -2 log likelihood than those
      without the addition of the term. Moreover, the area under the receiver-operating
      characteristic curve (AUC) analysis showed that the addition of CRP improved the
      AUC of each staging system. CONCLUSIONS: This study demonstrates that an elevated
      serum CRP level is independently associated with a poor prognosis in HCC
      patients, and the addition of the CRP level to the validated staging systems
      could improve the prognostic ability of each staging system.

PMID- 24924699
TI  - Emergency surgery for perforated diverticulitis in the immunosuppressed patient.
AB  - AIM: Immunosuppression is believed to worsen outcomes for patients who require
      surgery for perforated diverticulitis. The aim of this study was to compare
      surgical outcomes between immunocompromised and immunocompetent patients
      undergoing surgery for complicated diverticulitis. METHOD: All patients who
      underwent emergency surgery for complicated diverticulitis between 2004 and 2012
      in a single unit were studied. Patients were classified as immunosuppressed
      (group I) or immunocompetent (group II). Operation type and postoperative
      morbidity and mortality were compared between groups. The impact of operating
      surgeons' specialization and the Peritonitis Severity Score (PSS) were also
      evaluated to determine their impact on the restoration of gastrointestinal (GI)
      continuity. RESULTS: One-hundred and sixteen patients (mean age: 63.7 years),
      41.4% women, were included. Fifty-three (45.7%) patients were immunosuppressed
      (group I): 42 underwent Hartmann's procedure (HP) (79.2%), nine (17.0%) underwent
      resection and primary anastomosis (RPA) with ileostomy (IL) and two (3.8%)
      underwent RPA without IL. In group II, 15 HP (23.8%), nine RPA with IL (14.3%)
      and 39 RPA without IL (61.9%) were performed. Postoperative morbidity and
      mortality were 79.2% and 26.4%, respectively, in group I and 63.5% and 6.3%,
      respectively, in group II. The overall mean PSS was 9.5, with a mean PSS of 11.1
      in group I and of 8.1 in group II. The decision to perform a primary anastomosis
      differed significantly between colorectal surgeons and general surgeons in the
      patients with a PSS of 9-10-11. CONCLUSION: In immunocompromised patients, RPA
      with IL can be a safe surgical option, whereas HP should be reserved for patients
      with a PSS of > 11. Colorectal surgical specialization is associated with higher
      rates of restoration of GI continuity in patients with perforated diverticulitis,
      especially in patients with an intermediate PSS score. Evaluation of each
      patient's PSS facilitates decision making in surgery for perforated
      diverticulitis.

PMID- 24924701
TI  - Epilepsy, energy deficiency and new therapeutic approaches including diet.
AB  - Metabolic dysfunction leading to epilepsy is well recognised. Dietary therapy, in
      particular the ketogenic diet, is now considered an effective option. Recent
      genetic studies have highlighted the central role that metabolism can play in
      setting seizure susceptibility. Here we discuss various metabolic disorders
      implicated in epilepsy focusing on energy deficiency due to genetic and
      environmental causes. We argue that low, uncompensated brain glucose levels can
      precipitate seizures. We will also explore mechanisms of disease and therapy in
      an attempt to identify common metabolic pathways involved in modulating seizure
      susceptibility. Finally, newer therapeutic approaches based on diet manipulation
      in the context of energy deficiency are discussed. 

PMID- 24924702
TI  - The aesthetic approach to people with dementia.

PMID- 24924704
TI  - Association between compound heterozygous mutations of SLC34A3 and
      hypercalciuria.
AB  - BACKGROUND: Mutations in SLC34A3 have been shown to cause hereditary
      hypophosphatemic rickets with hypercalciuria (HHRH). Patients with compound
      heterozygous or homozygous mutations develop skeletal lesions in addition to
      hypercalciuria, hypophosphatemia and/or elevated 1,25-dihydroxy vitamin D [1,25
      (OH)2D] levels. Here, we report a case of hypercalciuria without skeletal lesions
      in a patient with compound heterozygous mutations of SLC34A3. CASE PRESENTATION:
      A 3-year-old girl presented with microscopic hematuria. Laboratory data revealed
      elevated 1,25-(OH)2D levels and serum calcium, reduced serum inorganic phosphorus
      and hypercalciuria. In addition, the ratio of maximal rate of renal tubular
      reabsorption of phosphate to glomerular filtration rate was reduced. Abdominal
      ultrasound revealed bilateral nephrocalcinosis. These data were consistent with
      HHRH, but the patient had no clinical features of rickets or any family history
      of skeletal disease. Genetic analysis revealed compound heterozygous mutations of
      c.175+1 G>A and c.1234 C>T in SLC34A3. CONCLUSIONS: This is the report of a
      patient with compound heterozygous mutations of SLC34A3 and normal skeletal
      features. Biallelic mutations in SLC34A3 can thus be associated with
      hypercalciuria not accompanied by rickets. Orally administered inorganic
      phosphate is predicted to improve symptoms in these patients, hence screening for
      SLC34A3 mutations should be considered in patients with hypercalciuria of unknown
      etiology.

PMID- 24924705
TI  - [The role of critical care medicine in rescue of Lushan earthquake].

PMID- 24924703
TI  - Improvements in gait characteristics after intensive resistance and functional
      training in people with dementia: a randomised controlled trial.
AB  - BACKGROUND: Preventing and rehabilitating gait disorders in people with dementia
      during early disease stage is of high importance for staying independent and
      ambulating safely. However, the evidence gathered in randomized controlled trials
      (RCTs) on the effectiveness of exercise training for improving spatio-temporal
      gait parameters in people with dementia is scarce. The aim of the present study
      was to determine whether a specific, standardized training regimen can improve
      gait characteristics in people with dementia. METHODS: Sixty-one individuals
      (mean age: 81.9 years) with confirmed mild to moderate stage dementia took part
      in a 3-month double-blinded outpatient RCT. Subjects in the intervention group
      (IG) received supervised, progressive resistance and functional group training
      for 3 months (2 times per week for two hours) specifically developed for people
      with dementia. Subjects in the control group (CG) conducted a low-intensity motor
      placebo activity program. Gait characteristics were measured before and after the
      intervention period using a computerized gait analysis system (GAITRite(r)).
      RESULTS: Adherence to the intervention was excellent, averaging 91.9% in the IG
      and 94.4% in the CG. The exercise training significantly improved gait speed (P <
      0.001), cadence (P = 0.002), stride length (P = 0.008), stride time (P = 0.001),
      and double support (P = 0.001) in the IG compared to the CG. Effect sizes were
      large for all gait parameters that improved significantly (Cohen's d: 0.80-1.27).
      No improvements were found for step width (P = 0.999), step time variability (P =
      0.425) and Walk-Ratio (P = 0.554). Interestingly, low baseline motor status, but
      not cognitive status, predicted positive training response (relative change in
      gait speed from baseline). CONCLUSION: The intensive, dementia-adjusted training
      was feasible and improved clinically meaningful gait variables in people with
      dementia. The exercise program may represent a model for preventing and
      rehabilitating gait deficits in the target group. Further research is required
      for improving specific gait characteristics such as gait variability in people
      with dementia. TRIAL REGISTRATION: ISRCTN49243245.

PMID- 24924706
TI  - [Critical care medicine and earthquake relief].

PMID- 24924700
TI  - Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac
      diseases: therapeutic perspectives.
AB  - Cardiovascular diseases cause more mortality and morbidity worldwide than any
      other diseases. Although many intracellular signaling pathways influence cardiac
      physiology and pathology, the mitogen-activated protein kinase (MAPK) family has
      garnered significant attention because of its vast implications in signaling and
      crosstalk with other signaling networks. The extensively studied MAPKs ERK1/2,
      p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms,
      responding to a myriad of mitogens and stressors and influencing the signaling of
      cardiac development, metabolism, performance, and pathogenesis. Definitive
      relationships between MAPK signaling and cardiac dysfunction remain elusive,
      despite 30 years of extensive clinical studies and basic research of various
      animal/cell models, severities of stress, and types of stimuli. Still, several
      studies have proven the importance of MAPK crosstalk with mitochondria,
      powerhouses of the cell that provide over 80% of ATP for normal cardiomyocyte
      function and play a crucial role in cell death. Although many questions remain
      unanswered, there exists enough evidence to consider the possibility of targeting
      MAPK-mitochondria interactions in the prevention and treatment of heart disease.
      The goal of this review is to integrate previous studies into a discussion of
      MAPKs and MAPK-mitochondria signaling in cardiac diseases, such as myocardial
      infarction (ischemia), hypertrophy and heart failure. A comprehensive
      understanding of relevant molecular mechanisms, as well as challenges for studies
      in this area, will facilitate the development of new pharmacological agents and
      genetic manipulations for therapy of cardiovascular diseases.

PMID- 24924707
TI  - [The changes of concept and practice in treatment of severe earthquake victims.
      From Wenchuan to Lushan].

PMID- 24924708
TI  - [Intensive care unit treatment strategy and algorithm for critical patients from
      Lushan earthquake].
AB  - OBJECTIVE: To explore the intensive care unit (ICU) strategy and algorithm of
      treatment for critical patients from the Lushan Earthquake. METHODS:
      Retrospective analyses were performed on the clinical characteristics and
      treatments for critical patients of Lushan Earthquake occurring on April 20,
      2013. A total of 18 critical patients were admitted into 3 ICUs of Sichuan
      Provincial People's Hospital. There were 8 females and 10 males with an average
      age of 46 +/- 23 years and a mean score of APACHE II 11 +/- 6. There were
      extremity fractures (n = 16, 88.9%), chest traumas (n = 11, 61.1%), head injuries
      (n = 8, 44.4%) and pelvic fractures (n = 9, 50%) . All of them received VIPC plan
      for early stage resuscitation and CRASHPLAN for further evaluations. And
      individual treatment was planned and implemented by multidisciplinary
      specialists. RESULTS: During ICU stay, 7 patients (38.9%) suffered acute
      respiratory distress syndrome (ARDS). Among them, noninvasive ventilation (n = 2)
      and intubation and mechanical ventilation (n = 5) were implemented. Ten septic
      patients (55.6%) received antibiotic therapy, 6 with severe head injury accepted
      Lund's concept for brain protection and 13 (72.2%) underwent 20 operations.
      Sixteen patients (88.9%) were discharged and another 2 (11.1%) remained comatose
      in hospital. CONCLUSION: Earthquake-related critical patients have complicated
      disease situations. And centralized salvage, optimal strategy and algorithm may
      improve their outcomes.

PMID- 24924709
TI  - [Value of focused critical ultrasound in the treatment of critical patients in
      Lushan earthquake].
AB  - OBJECTIVE: To explore the value of focused critical ultrasound in the treatment
      of critical patients in Lushan earthquake. METHODS: The utilization of bedside
      ultrasound and its effects on the treatment of critical patients in Lushan
      earthquake were retrospectively analyzed. RESULTS: After brief training of
      resident doctors, bedside ultrasound was performed for 107 sessions. And 97
      sessions (90.7%) of ultrasound exams were valuable for diagnosis and treatment.
      The exams included hemodynamic monitoring for 44 sessions and bedside lung
      ultrasound for 58 sessions. In hemodynamic monitoring, after heart function
      estimation, fluid resuscitation was restarted in 8 cases (8/44, 18.2%) and
      terminated in 2 cases to control risks. False estimate of volume by clinical
      experience were 8 sessions (8/44, 18.2%). And corrections were made after
      ultrasound exams. A total of 18 cases (18/44, 40.9%) of hemodynamic treatments
      improved with the help of focused critical ultrasound. Bedside lung ultrasound
      was performed to monitor the change of lung water in fluid resuscitation 6
      sessions and guide the pleural fluid drainage and lung recruitment before weaning
      17 sessions; the BLUE-plus lung ultrasound protocol was performed for 32
      sessions. And 24 cases of lung consolidation and atelectasis were found. Chest
      physiotherapy was then performed. The focused critical ultrasound exam was also
      performed to locate thrombus, biliary infection and intracranial infection, etc.
      CONCLUSION: Focused critical ultrasound can provide reliable clinical information
      to reduce unnecessary examination and optimize therapies for Lushan earthquake
      victims.

PMID- 24924710
TI  - [The changes of inflammatory cytokines and their clinical significance in
      patients of inferior ST-segment elevation acute myocardial infarction with
      anterior ST-segment depression].
AB  - OBJECTIVE: To investigate the level of Hs-CRP, Fib,IL-6, TNF-alpha,MDA, SOD, and
      analyse the correlation between the level of plasma inflammatory cytokines and
      clinical significance in patients with anterior ST-segment depression. METHODS:
      We choose 360 patients with inferior ST Segment elevation acute myocardial
      infarction from May 2007 to Sep 2012 in rescue Center of Anzhen Hospital, in
      Anzhen Hospital, and all the patients received percutaneous coronary intervention
      treatment and the vascular lesions besides culprit vessel were observed. All the
      patients were divided into two groups: control group (n = 180) and anterior ST
      segment depression group (n = 180). 8ml venous blood was obtained from all the
      patients, and then plasma were separated. The level of plasma Hs-CRP, Fib, IL-6,
      TNF-alpha, MDA, SOD were investigated by Biochemistry and ELISA. And the
      relativity between the level of plasma inflammatory cytokines and anterior ST
      segment depression in patients with inferior acute myocardial infarction was
      analysed. RESULTS: The proportion of double vessel coronary disease, three
      coronary artery lesion is higher in anterior ST-segment depression group compared
      with control group (P < 0.01) . Compared with control group, the level of Hs-CRP,
      Fib, IL-6, TNF-alpha,MDA, SOD of anterior ST-segment depression group are
      inclined significantly (P < 0.01). CONCLUSION: The level of plasma inflammatory
      cytokines and the degree of lipid peroxidation can reflect the severity of
      coronary artery disease and may have certain value in predicting the severity of
      disease.

PMID- 24924711
TI  - [Cancer clearance for "unprovoked" venous thromboembolism cases].
AB  - OBJECTIVE: To verify the significance of prospective serum cancer markers
      clearance program for primary Venous thromboembolism(VTE) cases. METHODS: During
      1 July 2010 within 31 Dec 2012, data from two Chinese vascular centers was
      prospective registry. All the cases diagnosed as primary VTE by first vascular
      physicians were underwent serum cancer markers clearance. Long term follow up was
      required to confirm real cancer occurrence and long term survival rate. A total
      of 167 cases (106 male and 61 female) were enrolled in this study. Mean age was
      52 +/- 15 years old. RESULTS: Eighteen cases (10.78%) were finally scanned as
      malignant. The sensitive of markers: Carcino-embryonic antigen (CEA) 0.67,
      carbohydrate antigen (CA)199 0.44, CA242 0.33, CA153 0.44, CA125 0.78, CA724
      0.17, combined markers 0.94. The specificity of above markers was 0.97,0.98,
      0.98, 0.97, 0.93, 0.97 and 0.86. CA 125 showed best sensitive and specificity as
      a sole marker. The positive likelihood ratio for markers: CEA 24.83 ((95%CI 8.95
      68.90), CA199 22.07 (95%CI 6.43-75.78), CA242 16.56 (95%CI 4.53-60.55), CA153
      13.24 (95%CI 4.85-36.17), CA125 10.54 (95%CI 5.67-19.58), CA 724 4.97(95%CI 1.29
      19.07), combined of markers 6.70 (95%CI 4.44-10.12). The negative likelihood
      ratio for markers: CEA 0.34 ((95%CI 0.18-0.66), CA199 0.57 (95%CI 0.37-0.86),
      CA242 0.68 (95%CI 0.49-0.94), CA153 0.57 (95%CI 0.38-0.87), CA125 0.24 (95%CI
      0.10-0.57), CA 724 0.86 (95%CI 0.76-1.06), combined of markers 0.66 (95%CI 0.01
      0.44). CEA+CA125 showed better positive and negative likelihood ratio. 6 months,
      12 months and 24 months survival rate for malignant (18cases) and non
      malignant(149cases) were 61.1%, 50.0%, 31.3% and 99.3%, 98.6%, 98.6%
      respectively. CONCLUSION: It is reasonable to screening malignant for
      "unprovoked" VTE cases. Combined multiple serum cancer markers showed best
      result. CA125 plus CEA showed acceptable result for some limited condition. CA50
      was useless for cancer screening.

PMID- 24924712
TI  - [Study on gene-gene, gene-environmental interactions of DNA repair genes related
      with age-related cataract].
AB  - OBJECTIVE: To investigate the interaction between polymorphisms and environment
      factors in age related cataract (ARC). METHODS: Population-based case-control
      study. All of 448 cataract cases were selected from cataract eye database and 248
      controls were recruited from Funing county. All 18 single nucleotide polymorphism
      (SNPs) of WRN, OGG1, BLM and ERCC6 genes were genotyped using real-time
      fluorescent quantitative PCR. The possible risk of ARC was estimated by
      unconditional Logistic regression. The interaction effects between gene-gene and
      gene-environment were evaluated by use of multifactor dimensionality reduction
      (MDR). RESULTS: Risk of ARC in illiterate group was significantly increased (OR =
      1.53, P < 0.05), compared to no illiterate group. The risk of cataract in farmers
      was significantly high with ORs of 3.75. Long exposure to sunlight may increase
      cataract risk. Factors such as smoking, drinking, hypertension had no
      relationship with ARC (P > 0.05). WRN-rs11574311 was still associated with ARC
      with statistical significance after Bonferroni correction (OR = 1.98, Pa<0.018).
      There was no evidence for any association at a significance level of P < 0.05 for
      the remaining alleles. MDR analysis showed a significant interaction model among
      the six factors: education, solar radiation, WRN-rs11574311, WRN-rs1801195, WRN
      rs4733220 and BLM-rs17273206 (consistency inspection accuracy of 0.683 on
      average, cross validation at 10/10, P = 0.005). Logistic regression model showed
      that the "high-risk" individuals had a significantly increased risk of ARC,
      compared to those "low- risk" individual classified by the MDR mode mentioned
      above(OR = 5.51, P < 0.05). CONCLUSION: WRN-rs11574311 allele was the risk factor
      for ARC, and individuals who carried WRN-rs1801195, WRN-rs4733220 and BLM
      rs17273206 allele and low level of education, long sunlight time significantly
      increased the risk of the ARC.

PMID- 24924713
TI  - [Survival analysis and recommendation of subdividing M1 stage according to
      metastatic status of colorectal cancer].
AB  - OBJECTIVE: To subdivide the M1 stage of patients to predict better survival
      groups and assess the predictive factors of prognosis to select personalized
      cancer treatments. METHODS: From the records of 666 colorectal cancer cases
      treated at our hospital during January 1995 to December 2010, we analyzed the
      site of metastases, number of metastases, size of hepatic metastatic tumor and
      corresponding treatments. According to the results, we made recommendations for
      subdividing the M1 stage to guide individualized treatments. RESULTS: The
      metastatic median survival of liver metastasis and non-liver metastasis were 18.7
      vs 22.9 months (P = 0.082). And the median survival of single organ metastasis,
      double organ metastasis and multiple organ metastasis were 24.8 vs 15.6 vs 10.9
      months, (P < 0.01).With no more than 3 liver lesions, the patients received
      operation or ablation therapy plus chemotherapy and their median survival was
      longer than those on chemotherapy only (49.6 vs 22.3 months, P < 0.01).
      CONCLUSION: According to metastatic characteristics, different clinical features
      and treatments result in significantly different survivals and prognoses in
      metastatic colorectal cancer patients.

PMID- 24924714
TI  - [Comparative study of X-ray digital tomosynthesis imaging based on intravenous
      urography and unenhanced multidetector-row computerized tomography in urinary
      calculi].
AB  - OBJECTIVE: To evaluate the clinical application value of X-ray digital
      DTSynthesis (DTS) based on IVU (Intravenous Urography)in urinary calculi
      contrasted with unenhanced multidetector-row computerized tomography. METHODS: 75
      patients suspected of urinary calculi underwent IVU, DTS based on IVU and UMDCT.
      The diagnostic sensitivity, specificity, accuracy, positive predictive value and
      negative predictive of the three imaging ways were acquired according to
      operations, respectively. Chi-square test was used to evaluate the difference
      among the three ways. RESULTS: In 75 cases, 60 cases were proved to be urinary
      calculi. The diagnostic sensitivity, specificity, accuracy, positive predictive
      value and negative predictive of IVU, DTS based on IVU,UMDCT is 70.0%, 73.3%,
      70.7%, 91.3%, 37.9%; 91.7%, 86.7%, 90.7%, 96.5%, 72.2%; 96.7%, 86.7%, 94.7%,
      96.7%, 86.7%, respectively.No significant differences between DTS based on IVU
      and UMDCT were found in sensitivity, specificity, accuracy, positive predictive
      value and negative predictive. Both cases are better than IVU in diagnostic
      ability. CONCLUSION: There is no significant difference in diagnostic ability of
      urinary calculi between DTS and UMDCT. DTS can be used as a routine imaging
      technique in diagnosis and follow up of urinary calculi.

PMID- 24924715
TI  - [Utility value of a T-cell interferon-gamma release assay based on recombinant
      Mycobacterium tuberculosis 11kD protein in the diagnosis of tuberculosis].
AB  - OBJECTIVE: To evaluate the diagnostic efficiency of a T-cell interferon-gamma
      release assay based on recombinant Mycobacterium tuberculosis (MTB) 11kD protein
      for diagnosing tuberculosis. METHODS: This prospective study enrolled inpatients
      with suspected tuberculosis at PUMCH to examine the diagnostic sensitivity,
      specificity, predictive value (PV) and likelihood ratio (LR) of T-cell interferon
      gamma release assays based on recombinant MTB-11kD protein, early antigenic
      target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides (T-SPOT. TB).
      Test results were compared with final clinical and microbiological diagnoses.
      RESULTS: Among 151 inpatients with suspected tuberculosis, 33 (21.9%) were
      microbiologically or clinically diagnosed as tuberculosis and 107 (70.9%) ruled
      out. And the remaining 11 (7.3%) patients were clinically indeterminate. The
      sensitivities of recombinant MTB-11kD-ELISPOT assay and T-SPOT. TB were 60.6%and
      81.8%respectively (P = 0.057).Whereas, the specificity of recombinant MTB-11kD
      ELISPOT assay was significantly higher than that of T-SPOT. TB (84.1%vs 72.9%, P
      = 0.046). The parallel testing increased the sensitivity to 84.9% and serial
      testing increased the specificity to 86.9%. CONCLUSION: The recombinant MTB-11kD
      ELISPOT assay is more specific than T-SPOT. TB. And its combination with T-SPOT.
      TB may improve the diagnostic efficiency for tuberculosis.

PMID- 24924717
TI  - [Clinical analysis of 56 patients with cervical cancer after cold knife
      conization].
AB  - OBJECTIVE: To evaluate the clinical value of conization in the diagnosis of
      cervical cancer to optimize its management. METHODS: Fifty-six patients diagnosed
      with cervical cancer after conization at our hospital between 2008 and 2012 were
      reviewed. The pathological profiles of colposcopic multiple biopsies and
      treatment options were analyzed. RESULTS: Among them, there were stage Ia1 (n =
      39), stage Ia2 (n = 2) and stage Ib1 (n = 15). And there was not much
      correspondence between cervical conization and colposcopic multiple biopsies in
      46 cases. Among 23 patients with stage Ia1 undergoing further surgery, 12
      (52.17%) had residual diseases, including CINI (n = 5), CINII(n = 3), CINIII (n =
      3). No recurrence was found in 16 cases without further surgical intervention.
      All cases of stages Ia2 and Ib1 underwent repeat surgery while 8 cases received
      preoperative chemotherapy, including stage Ia2 (n = 1) and stage Ib2 (n = 7).
      CONCLUSION: Cold knife conization plays a very important role in the diagnosis
      and treatment of cervical diseases. Further treatment options should be selected
      individually and comprehensively based on such factors as patient age, degrees of
      dysplasia, surgical margin status, fertility requirements and so on.

PMID- 24924716
TI  - [Preliminary clinical evaluations of bevacizumab for recurrent malignant glioma
      in Chinese patients].
AB  - OBJECTIVE: To explore the clinical efficacies of bevacizumab (BEV) for high-grade
      glioma (HGG) in Chinese patients and evaluate its profiles of adverse events and
      usage safety. METHODS: A total of 15 HGG cases, including glioblastoma multiform
      (GBM) (n = 12) and anaplastic astrocytoma (AA) (n = 3), were selected to receive
      the treatments of BEV (10 mg/kg, q2w) and temozolomide (TMZ, 150 mg/m(2), 5 d/28
      d). Their radiological responses, clinical status, progression-free survival
      (PFS) and overall survival (OS) were evaluated. Also their adverse events and
      severity were recorded and analyzed. RESULTS: According to the RANO criteria,
      during the short period (<3 months), 11 cases had significant radiological and
      clinical responses. However, only 4 cases responded during a follow-up period of
      beyond 3 months. Three cases had retrogression after BEV chemotherapy. At 6
      months post-treatment, 8 cases (53.3%) survived without lesion progression and
      the median PFS was 8 +/- 5 months. During a longer follow-up (>6 months), 8
      patients had tumor retrogression, including 5 deaths. The median overall survival
      period was 24 +/- 10 months. The adverse events included hypertension (n = 2),
      wound-healing complication (n = 1), vomiting (n = 2) and cerebro-spinal fluid
      leakage (n = 1). All complications were cured by activate supportive measures.
      CONCLUSION: After BEV treatment, most patients obtain more significant short-term
      responses with good toleration. For re-operative cases, the usage of BEV should
      be deferred to one month post-operation so as to avoid the occurrence of wound
      healing complications.

PMID- 24924718
TI  - [Modified approach to difficult vaginal hysterectomy].
AB  - OBJECTIVE: To explore the advantage, feasibility and safety of modified approach
      to difficult vaginal hysterectomy and provide scientific rationales for expanding
      its indications. METHODS: A retrospective study was conducted for 237 patients
      undergoing hysterectomy for benign disease of uterus (without prolapse) from
      January 2009 to July 2012. Both modified approach to difficult vaginal
      hysterectomy (TVH, n = 167) and abdominal hysterectomy (TAH, n = 70) were
      performed. Two groups were compared for epidemiological, clinical
      characteristics, operative duration, intraoperative blood loss volume,
      perioperative and postoperative complications, hospitalization duration,
      inflammatory response and follow-up outcomes. TVH was divided into 3 subgroups of
      enlarged uterus (n = 100), prior pelvic surgeries/endometriosis history (n = 25)
      and complicated cases with multiple factors (n = 42). Then the surgical outcome
      parameters were compared for each group. RESULTS: The operative duration,
      intraoperative blood loss volume and blood transfusion amount were significantly
      less in the TVH group than those in the TAH group (P < 0.05). No major
      perioperative complications occurred in either group. There was no conversion
      from TVH into TAH. Inflammatory response, gastrointestinal recovery and
      hospitalization duration for the TVH group were significantly shorter than those
      of the TAH group (P < 0.05). The hospitalization expense was almost the same in
      two groups (P > 0.05). Postoperative complications and the quality of sexual
      health were not statistically different between two groups at 1 month and 6
      months post-operation (P > 0.05). The data of three TVH subgroups were collected.
      The complicated cases with multiple factors group had longer hospitalization
      duration than the enlarged uterus and the prior pelvic surgeries/endometriosis
      history groups (P < 0.05). Similarly the volume of blood loss in the complicated
      cases with multiple factors group was significantly more than those of other two
      groups (P < 0.05). CONCLUSION: As one kind of mini-invasive surgery with less
      complications, higher safety and feasibility, modified approach to difficult
      vaginal hysterectomy offers shorter operative duration, less volume of blood loss
      and faster recovery.

PMID- 24924719
TI  - [Effects of varus of knee osteoarthritis on patellar position].
AB  - OBJECTIVE: To explore the effects of varus of knee osteoarthritis (OA) on
      patellar position. METHODS: A total of 19 patients (27 knees) underwent the
      examinations of anterior-posterior, lateral knee and axis of patellar X-ray at 30
      degrees , 45 degrees , 60 degrees  and each X-ray was measured. RESULTS: The
      ratio between length of patellar tendon and length of patellar, vertical distance
      of lower edge of patellar to tibial plateau and height of patellar, distance of
      lower edge of medial facet of patellar to anterior angle of tibia and height of
      patellar were different from normal values. Patellar moved medially during the
      process of bending from 30 degrees to 60 degrees . CONCLUSION: The patellar of
      knee OA patients with varus moves down and medially.

PMID- 24924720
TI  - [Effects of 12/15-lipoxygenase antisense oligonucleotide on peroxisome
      proliferator-activated receptor gamma translocation in primarily cultured
      cortical neurons after oxygen-glucose deprivation].
AB  - OBJECTIVE: To explore the effects of 12/15-lipoxygenase antisense oligonucleotide
      (asON-12/15-LOX) on OGD (oxygen-glucose deprivation)-induced PPARgamma
      (peroxisome proliferator-activated receptor gamma) expression and nuclear
      translocation in primarily cultured cortical neurons. METHODS: After a 48-h pre
      treatment of 12/15-LOX antisense oligonucleotide (asON), primarily cultured
      cortical neurons underwent 3-hour OGD followed by a 24-hour
      reperfusion.Immunofluorescent staining and Western blot were used to evaluate the
      expressions of 12/15-LOX and PPARgamma as well as the nuclear translocation of
      PPARgamma. RESULTS: Compared with the control group, the expressions of 12/15-LOX
      and PPARgamma whole protein were enhanced in OGD group (t = -3.72 and -6.79, P =
      0.03 and 0.04). And an increase of PPARgamma in nucleus (t = -4.67, P = 0.02)
      could be noted with a simultaneous reduction in cytosol (t = 3.40, P = 0.04)
      after OGD, indicating an induction of nuclear translocation by OGD. Compared with
      OGD group, a pre-treatment of asON-12/15-LOX dramatically attenuated OGD-induced
      increase in 12/15-LOX whole protein expression (t = 5.03, P = 0.02). Compared
      with OGD group, a pre-treatment of asON-12/15-LOX greatly reduced OGD-induced
      increase in PPARgamma total protein expression (t = 2.83, P = 0.04) and nuclear
      translocation (t = 7.05, P = 0.01 for nuclear protein; t = -5.47, P = 0.01 for
      cytosol protein). It indicated a possible link between 12/15-LOX and PPARgamma.
      CONCLUSION: 12/15-LOX antisense oligonucleotide suppresses the expression and
      nuclear translocation of PPARgamma in primarily cultured cortical neurons after
      OGD.

PMID- 24924721
TI  - [LINGO-1 expression of brain tissue in experimental autoimmune encephalomyelitis
      mouse].
AB  - OBJECTIVE: To observe the changes of LINGO-1 expression with time after onset in
      EAE mouse. METHODS: C57/BL6 mice were completely randomly divided into EAE model
      group (n = 15) , adjuvant group (n = 15) and control group (n = 15) .LINGO-1
      expression of brain tissue was detected on day 1, 7, 14, 21 and 30 after onset by
      RT-PCR and Western blot.RhoA and p-RhoA expression of brain tissue was analysed
      by Western blot. RESULTS: The LINGO-1mRNA levels in EAE model group were markedly
      higher than control group on day 1, 7and 14 after onset (4.63 +/- 0.25, 2.72 +/-
      0.12, 1.98 +/- 0.16, P < 0.01, P < 0.01, P < 0.05).On day 30, Lingo-1 mRNA was
      close to control group.Expression levels of Lingo-1 protein on day 1, 7, 14, 21,
      30 were higher than control group (2.11 +/- 0.15, 3.15 +/- 0.09, 2.45 +/- 0.12,
      1.89 +/- 0.17, 1.21 +/- 0.05, P < 0.05, P < 0.01, P < 0.05, P < 0.05, P < 0.05.
      The levels of p-RhoA protein increased in EAE and the peak appeared on day 1 and
      day 7 (P < 0.01) . And there was no difference on RhoA expression among different
      groups. CONCLUSIONS: LINGO-1 expression of brain tissue of EAE mouse upregulates
      and changes with time after onset, which may inhibit myelination by RhoA
      activation.In clinic, the antagonist of LINGO-1 for MS should be applied as soon
      as possible.

PMID- 24924722
TI  - [White matter injury of spinal cord in rats with chronic fluorosis and recovery
      after defluoridation].
AB  - OBJECTIVE: To explore the injury mechanism for white matter of spinal cord and
      the improvement of function after defluoridation. METHODS: A total of 120 Wistar
      rats were separated randomly into 4 groups (n = 30 each). High flouriod group
      received high concentration NaF water (200 mg/L) to establish fluorosis model;
      control group distilled water; defluoridation group high concentration NaF water
      (200 mg/L) for 12 weeks and then distilled water for 12 weeks; defluoridation
      control group. The urinary contents of fluoride were detected at Weeks 4, 8 and
      12. The first two groups were sacrificed at Week 12 while the other two groups at
      Week 24. The spinal cord functions were detected by BBB scale and incline plate
      test. Their cervical spinal cord tissues were collected and observed under
      electron microscope. The expression of myelin basic protein (MBP) in thoracic
      cord was detected by immunohistochemistry and Western blot. The comparison of
      measurement data was performed with F test and correlation analysis. Cytological
      changes of white matter in spinal cord were detected after chronic fluorosis.
      RESULTS: The spinal functions of high flouriod and defluoridation groups were
      inferior to those of the control groups. But no difference existed among the
      groups. Pathological manifestations of chronic white matter injury of spinal cord
      could be found in high flouriod and defluoridation groups. The MBP expression in
      spinal cord of fluorosis and defluoridation groups decreased in comparison with
      those in control groups. But no difference existed among them. CONCLUSION: White
      matter injury of spinal cord is present in chronic fluorosis rats. Defluoridation
      for a short time offers no recovery.

PMID- 24924723
TI  - [Immunosuppressive action of dendritic cells sensitized by oligodeoxynucleotides
      and CA125 on human OVCAR3 ovarian carcinoma xenografts in nude mice].
AB  - OBJECTIVE: To explore the immunosuppressive action of dendritic cells (DC)
      sensitized by oligodeoxynucleotides containing "un-methylated cytosine
      phosphodiester bond-guanylic acid" motif (CpG ODN) and CA125 on human ovarian
      carcinoma xenografts in nude mice. METHODS: Human peripheral blood-derived
      dendritic cells were isolated and identified by flow cytometry. The DC sensitized
      by CpG ODN and CA125 were then co-cultured with T cells and finally cytotoxic T
      lymphocytes (CTL) were induced. Nude mice bearing OVCAR3 transplanted tumor were
      immunized with induced CTL by subcutaneous injection and tumor growth and cell
      apoptosis observed. RESULTS: Premature DC had a low expression of CD83 and CD86.
      In vivo, delayed growth of OVCAR3 xenografts was observed after immunotherapy
      with CTL induced by DC pulsed by CpG ODN and CA125. The inhibition rate of tumor
      was 50.71% and it was better than CpG ODN-pulsed and CA125-pulsed groups (P <
      0.05). Cell apoptotic rate was (29.6 +/- 3.0)% in CpG ODN+CA125-pulsed group
      versus (21.8 +/- 2.7)% in CpG ODN-pulsed group. And both were more than those of
      unpulsed and CA125-pulsed groups (P < 0.05). CONCLUSION: CTL induced by DC
      sensitized by CpG ODN and CA125 can inhibit the growth of ovarian carcinoma
      xenografts and promote tumor cell apoptosis.

PMID- 24924724
TI  - [Orthopedic rheumatology: conservative therapy and arthrology].

PMID- 24924725
TI  - [Technological orthopedic treatment of feet destroyed by rheumatism. Update].
AB  - BACKGROUND: The course of rheumatoid arthritis often leads to afflictions of the
      feet with typical deformities and complaints. In addition to the basis
      medication, physical therapy, physiotherapy and local infiltration techniques,
      technological orthopedic shoe treatment is an important component of conservative
      therapy. MATERIAL AND METHODS: This review article presents the foundations of
      the pathomechanics of rheumatic feet and the principles of treatment. RESULTS AND
      CONCLUSION: Through a sensible implementation of a foot disorder orthosis it is
      possible to mitigate deformities due to rheumatoid arthritis and also positively
      influence the further course. The aim of a foot disorder orthosis is ultimately
      to delay or even avoid surgical measures for rheumatic feet and also to stabilize
      the results after surgical interventions.

PMID- 24924726
TI  - [Polymyalgia rheumatica in daily routine practice].
AB  - DEFINITION AND EPIDEMIOLOGY: Polymyalgia rheumatica (PMR) is a very painful
      inflammatory disease which regularly affects the shoulder region but in 70% of
      cases the pelvic girdle region is also affected. The disease occurs in people
      over the age of 50 years and reaches a peak at 72 years old. Women are affected
      twice as often as men. The prevalence is estimated to be 0.3-0.7% in the
      Caucasian population over 50 years old. DIAGNOSTICS AND CLASSIFICATION:
      Misdiagnosis of PMR is common. The differential diagnosis primarily includes
      impingement syndrome, osteoarthritis of the shoulders, calcifying tendinitis of
      the rotator cuff, bursitis, omarthritis or inflammatory rheumatic diseases, such
      as rheumatoid arthritis. Taking a structured medical history and performing a
      thorough clinical examination are crucial. The erythrocyte sedimentation rate
      (ESR) and C-reactive protein (CRP) levels are usually highly elevated and should
      be investigated particularly in patients who present with new onset bilateral
      shoulder pain and pronounced general impairment of movement. Imaging shows
      characteristic inflammatory changes around the shoulders and hip joints. The new
      European League Against Rheumatism and American College of Rheumatology
      (EULAR/ACR) classification criteria of PMR including ultrasound imaging are
      superior to previous classification and diagnostic criteria in terms of positive
      and negative predictive values. THERAPY: Glucocorticoids are still the mainstay
      of treatment. Recommended daily prednisolone starting doses are between 15 mg and
      25 mg with a weekly dose reduction until 10 mg/day and then further dose
      reductions of 1 mg per month. Methotrexate can aid reducing prednisolone doses in
      patients who fail to reach doses below the Cushing threshold quickly enough,
      which can have major side effects.

PMID- 24924727
TI  - [Chondrocalcinosis. Clinical impact of intra-articular calcium phosphate
      crystals].
AB  - Calcium pyrophosphate dihydrate (CPPD) crystals are known to cause acute attacks
      of pseudogout in joints but crystal deposition has also been reported to be
      associated with osteoarthritis (OA). Aside from CPPD crystals, basic calcium
      phosphates (BCPs), consisting of carbonate-substituted hydroxyapatite (HA),
      tricalcium phosphate and octacalcium phosphate, have been found in synovial
      fluid, synovium and cartilage of patients with OA. Although CPPD crystals have
      been found to be associated with OA and are an important factor in joint disease,
      this has also recently been associated with a genetic defect. However, according
      to the most recent findings, the association of BCP crystals, such as apatite
      with OA is much stronger, as their presence significantly correlates with the
      severity of cartilage degeneration. Identification of BCP crystals in OA joints
      remains problematic due to a lack of simple and reliable methods of detection.
      The clinical and pathological relevance of cartilage mineralization in patients
      with OA is not completely understood. It is well established that mineralization
      of articular cartilage is often found close to hypertrophic chondrocytes. A
      significant correlation between the expression of type X collagen, a marker for
      chondrocyte hypertrophy and cartilage mineralization was observed. In the process
      of endochondral ossification, the link between hypertrophy and matrix
      mineralization is particularly well described. Hypertrophic chondrocytes in OA
      cartilage and at the growth line share certain features, not only hypertrophy but
      also a capability to mineralize the matrix. Recent data indicate that chondrocyte
      hypertrophy is a key factor in articular cartilage mineralization strongly linked
      to OA and does not characterize a specific subset of OA patients, which has
      important consequences for therapeutic strategies for OA. 

PMID- 24924728
TI  - [Severe osteoarthritic manifestations of ochronosis].
AB  - The congenital form of ochronosis is a result of the rare autosomal recessive
      inherited metabolic disease alkaptonuria. The disruption of tyrosine metabolism
      based on a genetic defect in the enzyme homogentisate dioxygenase results in
      accumulation of homogentisic acid (HA) which is excreted in the urine and leads
      to a dark discoloration after a certain incubation time at room temperature.
      Furthermore, HA polymerizes forming a pigment that is deposited in connective
      tissues such as tendons, cartilage, bones, intervertebral discs, sclerae,
      ossicles, cardiac valves and coronary arteries and leads to dark brown
      discoloration and degeneration. The case of a 74-year-old female patient with
      ochronosis and classical manifestations is described and in addition a current
      overview of this rare disease is provided. 

PMID- 24924729
TI  - [Hand ergotherapy for rheumatic diseases and the special importance of hand
      surgery].
AB  - BACKGROUND: Human hands play an important role in overcoming routine daily life.
      As a consequence of limitations in the function of the hand due to rheumatic
      diseases, various manual activities can become an enormous challenge or even
      become absolutely impossible. MATERIAL AND METHODS: This review article discusses
      the possibilities of hand ergotherapy and explains the most important assist
      devices. RESULTS AND CONCLUSION: The main area of occupational and hand therapy
      interventions in patients with rheumatoid arthritis is the postoperative or
      conservative treatment of wrist and finger joints. The main areas of concern are
      to maintain the mobility of the joints, when necessary and possible mobilization
      of the joints, strengthen the muscles, the prophylaxis or correction of
      deformities with thermoplastic splints, conservative pain relief and anti
      inflammatory treatment, joint protection precautions and teaching of home
      exercises for prophylaxis of contracture. Further areas of therapy are
      instruction and provision of adaptive devices for limitations of the upper and/or
      lower extremities, especially training of activities of daily living (ADL) and
      patient education.

PMID- 24924730
TI  - [Sport and rheumatoid arthritis].
AB  - BACKGROUND: Sport is becoming increasingly more important in our society. Due to
      the changing age spectrum with a greater number of elderly and substantially more
      active people, an increasing number of people with underlying orthopedic diseases
      are becoming interested in participating in sport. MATERIAL AND METHODS: This
      article deals with the possibilities and effects of sporting activities for
      people with rheumatoid arthritis within the framework of a conservative therapy.
      A literature search was carried out using medical search engines, in particular
      PubMed, and also via the recommendations of specialist societies and patient help
      groups. RESULTS: The quality of life of patients with rheumatoid arthritis
      consists of physical, mental and social components. Sport as a means of
      rehabilitation influences all of these components. Sport should be comprehended
      as a form of therapy and be adapted to the needs of the individual patient. The
      willingness to actively participate in sport should always be highly rated and
      encouraged. Sport is therefore an important pillar of therapy in a conservative
      total concept. The main aspects of sport therapeutic activities are functional,
      pedagogical and experience-oriented aspects. The clinical symptoms, extent of
      damage and physical impairment must, however, be evaluated and taken into
      consideration for the therapeutic concept. CONCLUSION: The amount of data on the
      complex topic of sport and rheumatoid arthritis is low and is mainly dealt with
      as retrospective reviews. A prospective randomized study basis is lacking. The
      aim must therefore be to confirm the currently available recommendations for
      various types of sport in controlled studies.

PMID- 24924731
TI  - [Large vessel vasculitis].
AB  - Giant cell arteritis (GCA) and Takayasu arteritis (TA) are the two diseases
      characterized as large vessel vasculitis (LVV) and are autoimmune diseases with
      granulomatous inflammation that affect medium and large sized arteries. These
      diseases are accompanied by symptoms of systemic inflammatory reactions typically
      including fatigue, weight loss and low grade fever as well as elevation of the
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. More
      specific symptoms include headache and visual symptoms for GCA and arm or leg
      claudication, renal hypertension and angina pectoris for TA. Imaging studies to
      demonstrate inflammatory vascular wall lesions and biopsy of the temporal artery
      for GCA are the most relevant diagnostic procedures. Treatment relies mainly on
      glucocorticoids. Methotrexate seems to have a moderate glucocorticoid-sparing
      effect but evidence for other immunosuppressants, including azathioprine,
      tocilizumab and cyclophosphamide is limited. Revascularization methods might also
      be required in TA. 

PMID- 24924732
TI  - [Mechanisms of fibrosis and their translation into clinical aspects].

PMID- 24924733
TI  - [Diagnosis and treatment of Lyme arthritis. Recommendations of the
      Pharmacotherapy Commission of the Deutsche Gesellschaft fur Rheumatologie (German
      Society for Rheumatology)].
AB  - These guidelines summarize the current evidence for diagnosis and treatment of
      Lyme arthritis and the most frequent skin manifestations of Borrelia burgdorferi
      infections. Lyme arthritis is a monoarticular or oligoarticular form of arthritis
      that typically involves the knee. A positive enzyme-linked immunosorbent assay
      (ELISA) for IgG antibodies should be followed by an IgG immunoblot. A positive
      PCR test from synovial fluid adds increased diagnostic certainty. Serum
      positivity for antibodies to Borrelia burgdorferi without typical symptoms does
      not justify antibiotic treatment. Oral antibiotic treatment for erythema migrans
      is recommended using doxycycline, 200 mg once per day for 10-21 days, alternative
      choices are amoxicillin, cefuroxime and azithromycin. For children below 8 years
      of age, amoxicillin is recommended.Lyme arthritis can usually be successfully
      treated with orally administered antimicrobial agents. Doxycycline, 1 * 200 or 2
      * 100 mg for 30 days is the antibiotic agent of choice. Amoxicillin (3 * 500-1000
      mg) can be alternatively chosen. Patients who have persistent or recurrent joint
      swelling after a recommended course of oral antibiotic therapy should be treated
      intravenously. In this situation, ceftriaxone at 2 g per day for 14-21 days is
      recommended. There is no evidence to recommend long-term and combined treatments.

PMID- 24924734
TI  - Cerebellar transcranial magnetic stimulation: the role of coil geometry and
      tissue depth.
AB  - BACKGROUND: While transcranial magnetic stimulation (TMS) coil geometry has
      important effects on the evoked magnetic field, no study has systematically
      examined how different coil designs affect the effectiveness of cerebellar
      stimulation. HYPOTHESIS: The depth of the cerebellar targets will limit
      efficiency. Angled coils designed to stimulate deeper tissue are more effective
      in eliciting cerebellar stimulation. METHODS: Experiment 1 examined basic input
      output properties of the figure-of-eight, batwing and double-cone coils, assessed
      with stimulation of motor cortex. Experiment 2 assessed the ability of each coil
      to activate cerebellum, using cerebellar-brain inhibition (CBI). Experiment 3
      mapped distances from the scalp to cerebellar and motor cortical targets in a
      sample of 100 subjects' structural magnetic resonance images. RESULTS: Experiment
      1 showed batwing and double-cone coils have significantly lower resting motor
      thresholds, and recruitment curves with steeper slopes than the figure-of-eight
      coil. Experiment 2 showed the double-cone coil was the most efficient for
      eliciting CBI. The batwing coil induced CBI only at higher stimulus intensities.
      The figure-of-eight coil did not elicit reliable CBI. Experiment 3 confirmed that
      cerebellar tissue is significantly deeper than primary motor cortex tissue, and
      we provide a map of scalp-to-target distances. CONCLUSIONS: The double-cone and
      batwing coils designed to stimulate deeper tissue can effectively stimulate
      cerebellar targets. The double-cone coil was found to be most effective. The
      depth map provides a guide to the accessible regions of the cerebellar volume.
      These results can guide coil selection and stimulation parameters when designing
      cerebellar TMS studies.

PMID- 24924735
TI  - Prevalence and characteristics of coronary-cameral communications in adult
      patients: coronary angiographic analysis of 16,573 patients.
AB  - OBJECTIVE: To analyze the coronary angiograms of patients with symptomatic heart
      disease in order to determine the frequency and characteristics of coronary
      cameral communications (CCCs) in a single center. SUBJECTS AND METHODS: The
      coronary angiograms of 16,573 patients with symptomatic heart disease performed
      from November 2001 to January 2011 were analyzed. The diagnosis of coronary
      fistula and coronary-cameral microcommunications (CCMCs) was made according to
      previously defined criteria. RESULTS: Of the 16,573 patients, 15 (0.09%; 8 males
      and 7 females, mean age 63 +/- 12 years) had CCCs, while coronary fistulas were
      identified in 2 (0.01%). In the first patient, the coronary fistula arose from
      the branches of the left anterior descending (LAD) artery and the right coronary
      artery (RCA) and drained into the right ventricle. In the second patient, the
      fistula originated from branches of the LAD artery, the circumflex (Cx) artery
      and the RCA and drained into the left ventricle. In 7 patients, the CCMCs
      originated from the LAD artery. In 3 patients, the Cx artery was the origin. The
      CCMCs originated from the RCA in 2 patients. In 1 patient the CCMC took its
      origin from the RCA and the Cx artery, while in 2 patients the CCMCs were
      associated with intracardiac masses in the left atrium and the right atrium,
      respectively. CONCLUSION: The prevalence of CCCs in adult patients was low and
      that of large coronary fistulas was even lower; coronary fistulas are probably
      very rare in adult patients because the majority of them are detected and treated
      during childhood.

PMID- 24924736
TI  - Monte-Carlo simulations of PAMAM dendrimer-DNA interactions.
AB  - We use Monte Carlo simulations to determine the influence of poly(amido amine)
      (PAMAM) dendrimer size and charge on its interactions with double-stranded DNA
      conformation and interaction strength. To achieve a compromise between simulation
      speed and molecular detail, we combine the coarse-grained DNA model of de Pablo
      et al. which resolves each DNA base using three beads - and thereby retains the
      double-helix structure - with a dendrimer model with resolution similar to that
      of the DNA. The resulting predictions of the effects of dendrimer generation,
      dendrimer surface charge density, and salt concentration on dendrimer-DNA
      complexes are in agreement with both experiments and all-atom MD simulations. The
      model predicts that DNA wraps a fully charged G5 or G6 dendrimer at low salt
      concentration (10 mM) similarly to a histone octamer, and for the G5 dendrimer,
      DNA super helices with both handednesses occur. At salt concentrations above 50
      mM, or when a high fraction of dendrimer surface charges are neutralized by
      acetylation, DNA adheres but does not compactly wrap the dendrimer, in agreement
      with experimental findings. We are also able to simulate pairs of dendrimers
      binding to the same DNA strand. Thus, our mesoscale simulation not only
      elucidates dendrimer-DNA interactions, but also provides a methodology for
      efficiently simulating chromatin formation and other cationic macroion-DNA
      complexes. 

PMID- 24924737
TI  - Post-traumatic pelvic splenosis diagnosed with a combination of laparoscopy and
      technetium 99m red blood cell scintigraphy.

PMID- 24924738
TI  - Pontocerebellar hypoplasia.
AB  - Pontocerebellar hypoplasia (PCH) is a clinically and genetically heterogeneous
      group of autosomal recessively inherited neurodevelopmental disorders. Following
      the rapidly increasing number of genes identified in different subtypes, the
      clinical spectrum has been broadened to completely different neurological
      phenotypes. In this review we will address the clinical picture,
      neuroradiological, pathoanatomic, and genetic findings in the currently known PCH
      subtypes.

PMID- 24924739
TI  - The response of the neuronal adaptive system to background illumination and
      readaptation to dark in the immature retina.
AB  - PURPOSE: Developmental characteristics of the neuronal adaptive system of the
      retina, focusing on background light (BGL) adaptation and readaptation functions,
      were studied by measuring the oscillatory response (SOP) of the electroretinogram
      (ERG). METHODS: Digitally filtered and conventional ERGs were simultaneously
      recorded. Rats aged 15 and 17 days were studied during exposure to BGLs of two
      mesopic intensities and during readaptation to dark. RESULTS: Results were
      compared to adult rats. In 'low mesopic' BGL SOP instantly dropped significantly
      to about half of its dark-adapted (DA) value contrary to mature rats, in which
      the SOP significantly increased. In 'high mesopic' BGL SOP decreased to about 20%
      and 30% of DA values in immature and adult rats, respectively. The process of
      recovery of SOP in darkness lacked the transient enhancement immediately as BGL
      was turned off, characteristic of adult rats. There were no major age differences
      in adaptive behaviour of a-wave. In young rats, recovery of b-wave was relatively
      slower. CONCLUSIONS: Properties of BGL adaptation and readaptation functions of
      the neuronal adaptive system in baby retina differed compared to the adult one by
      being less forceful and more restrained. Handling of mesopic illumination and
      recovery in the dark was immature. Development of these functions of the neuronal
      adaptive system progresses postnatally and lags behind that of the photoreceptor
      response and seems to be delayed also compared to that of the bipolar response.

PMID- 24924740
TI  - Kjellin syndrome: hereditary spastic paraplegia with pathognomonic macular
      appearance.

PMID- 24924741
TI  - Assessing the relative importance of local and regional processes on the survival
      of a threatened salmon population.
AB  - Research on regulatory mechanisms in biological populations often focuses on
      environmental covariates. An integrated approach that combines environmental
      indices with organismal-level information can provide additional insight on
      regulatory mechanisms. Survival of spring/summer Snake River Chinook salmon
      (Oncorhynchus tshawytscha) is consistently low whereas some adjacent populations
      with similar life histories experience greater survival. It is not known if
      populations with differential survival respond similarly during early marine
      residence, a critical period in the life history. Ocean collections, genetic
      stock identification, and otolith analyses were combined to evaluate the growth
      mortality and match-mismatch hypotheses during early marine residence of
      spring/summer Snake River Chinook salmon. Interannual variation in juvenile
      attributes, including size at marine entry and marine growth rate, was compared
      with estimates of survival and physical and biological metrics. Multiple linear
      regression and multi-model inference were used to evaluate the relative
      importance of biological and physical metrics in explaining interannual variation
      in survival. There was relatively weak support for the match-mismatch hypothesis
      and stronger evidence for the growth-mortality hypothesis. Marine growth and size
      at capture were strongly, positively related to survival, a finding similar to
      spring Chinook salmon from the Mid-Upper Columbia River. In hindcast models,
      basin-scale indices (Pacific Decadal Oscillation (PDO) and the North Pacific Gyre
      Oscillation (NPGO)) and biological indices (juvenile salmon catch-per-unit-effort
      (CPUE) and a copepod community index (CCI)) accounted for substantial and similar
      portions of variation in survival for juvenile emigration years 1998-2008
      (R2>0.70). However, in forecast models for emigration years 2009-2011, there was
      an increasing discrepancy between predictions based on the PDO (50-448% of
      observed value) compared with those based on the NPGO (68-212%) or biological
      indices (CPUE and CCI: 83-172%). Overall, the PDO index was remarkably
      informative in earlier years but other basin-scale and biological indices
      provided more accurate indications of survival in recent years. 

PMID- 24924742
TI  - Health-related quality of life in atrial fibrillation patients over 65 years: A
      review.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia affecting 1
      2% of the population; the prevalence of atrial fibrillation increases with
      ageing. The condition is associated with high morbidity and mortality, as well as
      reduced health-related quality of life, particularly in older people. A PubMed,
      CINAHL, EMBASE and CENTRAL search (January 2003 to April 2013) was conducted
      using the search terms atrial fibrillation, quality of life, health-related
      quality of life, older, aged, and over 65 years. In total, 572 papers were
      identified of which 15 were eligible, including three observational studies, five
      descriptive comparative studies and seven randomized control trials. Older atrial
      fibrillation patients (>=65 years) were significantly impaired in their health
      related quality of life in both physical and mental domains compared to the
      general population or patients with sinus rhythm. Increasing age, being female or
      having severe symptoms resulted in poorer health-related quality of life
      particularly in the physical domain. The review also found that the current
      treatment of AF including rate and rhythm control strategies improved some
      aspects of health-related quality of life in atrial fibrillation patients but no
      specific strategy had a superior effect. 

PMID- 24924743
TI  - Winning or losing does matter: Acute cardiac admissions in New Zealand during
      Rugby World Cup tournaments.
AB  - AIM: The relationship between watching major sporting events and cardiac hospital
      admissions is contentious. This study is the first to investigate cardiovascular
      admissions during Rugby World Cup (RWC) tournaments. METHODS AND RESULTS: New
      Zealand (NZ) public hospital admissions data were analysed for cardiovascular
      events during the 1999, 2003, 2007 and 2011 RWC tournaments. The exposure period
      was the day of the NZ All Blacks last match and 2 days post-match. The control
      period was equivalent days in October or November for 3 years prior to or after
      each RWC. The NZ 2011 semi-final win and 2000 Olympics opening ceremony were also
      analysed. There were 281 +/- 14 and 3313 +/- 379 cardiac admissions in the
      exposure and control periods. The semi-final loss in 2003 was associated with a
      50% (p < 0.01) increase in pooled heart failure admissions and a 20% (p < 0.05)
      increase in pooled acute coronary syndromes admissions. Increases in heart
      failure were specific to women with a two-fold increase on match day and 2-days
      post (p < 0.01). There was no increase in male heart failure admissions but
      arrhythmias increased 2.6 times (p < 0.01) 1-day after losing the 2003 semi
      final. In contrast, admissions were typically lower after the 2011 semi-final win
      and Olympics opening ceremony. CONCLUSION: This is the first study to find a
      relationship between hospital admissions for heart failure in women and a major
      sporting event. Preventive health measures should be considered in fans with
      cardiovascular disease or at high risk of cardiovascular events during sporting
      events. Winning or losing does matter.

PMID- 24924744
TI  - Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human
      acute liver injury.
AB  - Several serum markers are used to assess hepatocyte damage, but they have
      limitations related to etiology specificity and prognostication. Identification
      of novel hepatocyte-specific biomarkers could provide important prognostic
      information and better pathogenesis classification. We tested the hypothesis that
      hepatocyte-selective biomarkers are released after subjecting isolated mouse
      hepatocytes to Fas-ligand-mediated apoptosis. Proteomic analysis of hepatocyte
      culture medium identified the mitochondrial matrix protein carbamoyl phosphate
      synthetase-1 (CPS1) among the most readily detected proteins that are released by
      apoptotic hepatocytes. CPS1 was also detected in mouse serum upon acute challenge
      with Fas-ligand or acetaminophen and in hepatocytes upon hypoosmotic stress,
      independent of hepatocyte caspase activation. Furthermore, CPS1 was observed in
      sera of mice chronically fed the hepatotoxin 3,5-diethoxycarbonyl-1,4
      dihydrocollidine. Mouse CPS1 detectability was similar in serum and plasma, and
      its half-life was 126 +/- 9 min. Immune staining showed that CPS1 localized to
      mouse hepatocytes but not ductal cells. Analysis of a few serum samples from
      patients with acute liver failure (ALF) due to acetaminophen, Wilson disease, or
      ischemia showed readily detectable CPS1 that was not observed in several patients
      with chronic viral hepatitis or in control donors. Notably, CPS1 rapidly
      decreased to undetectable levels in sera of patients with acetaminophen-related
      ALF who ultimately recovered, while alanine aminotransferase levels remained
      elevated. Therefore, CPS1 becomes readily detectable upon hepatocyte apoptotic
      and necrotic death in culture or in vivo. Its abundance and short serum half
      life, compared with alanine aminotransferase, suggest that it may be a useful
      prognostic biomarker in human and mouse liver injury. 

PMID- 24924745
TI  - Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential
      hepatic metabolic function.
AB  - Nonalcoholic steatohepatitis (NASH) is increasing in prevalence, yet its
      consequences for liver function are unknown. We studied ureagenesis, an essential
      metabolic liver function of importance for whole body nitrogen homeostasis, in a
      rodent model of diet-induced NASH. Rats were fed a high-fat, high-cholesterol
      diet for 4 and 16 wk, resulting in early and advanced experimental NASH,
      respectively. We examined the urea cycle enzyme mRNAs in liver tissue, the
      hepatocyte urea cycle enzyme proteins, and the in vivo capacity of urea-nitrogen
      synthesis (CUNS). Early NASH decreased all of the urea cycle mRNAs to an average
      of 60% and the ornithine transcarbamylase protein to 10%, whereas the CUNS
      remained unchanged. Advanced NASH further decreased the carbamoyl phosphate
      synthetase protein to 63% and, in addition, decreased the CUNS by 20% [from 5.65
      +/- 0.23 to 4.58 +/- 0.30 MUmol * (min * 100 g)(-1); P = 0.01]. Early NASH
      compromised the genes and enzyme proteins involved in ureagenesis, whereas
      advanced NASH resulted in a functional reduction in the capacity for ureagenesis.
      The pattern of urea cycle perturbations suggests a prevailing mitochondrial
      impairment by NASH. The decrease in CUNS has consequences for the ability of the
      body to adjust to changes in the requirements for nitrogen homeostasis e.g., at
      stressful events. NASH, thus, in terms of metabolic consequences, is not an
      innocuous lesion, and the manifestations of the damage seem to be a continuum
      with increasing disease severity. 

PMID- 24924746
TI  - Defining hierarchies of stemness in the intestine: evidence from biomarkers and
      regulatory pathways.
AB  - For decades, the rapid proliferation and well-defined cellular lineages of the
      small intestinal epithelium have driven an interest in the biology of the
      intestinal stem cells (ISCs) and progenitors that produce the functional cells of
      the epithelium. Recent and significant advances in ISC biomarker discovery have
      established the small intestinal epithelium as a powerful model system for
      studying general paradigms in somatic stem cell biology and facilitated elegant
      genetic and functional studies of stemness in the intestine. However, this
      newfound wealth of ISC biomarkers raises important questions of marker
      specificity. Furthermore, the ISC field must now begin to reconcile biomarker
      status with functional stemness, a challenge that is made more complex by
      emerging evidence that cellular hierarchies in the intestinal epithelium are more
      plastic than previously imagined, with some progenitor populations capable of
      dedifferentiating and functioning as ISCs following damage. In this review, we
      discuss the state of the ISC field in terms of biomarkers, tissue dynamics, and
      cellular hierarchies, and how these processes might be informed by earlier
      studies into signaling networks in the small intestine. 

PMID- 24924747
TI  - Gliadin intake alters the small intestinal mucosa in indomethacin-treated HLA-DQ8
      transgenic mice.
AB  - Celiac disease (CD) is an enteropathy caused by the ingestion of wheat gluten in
      genetically susceptible individuals. A complete understanding of the pathogenic
      mechanisms in CD has been hindered because of the lack of adequate in vivo
      models. In the present study, we explored the events after the intragastric
      administration of gliadin and of the albumin/globulin fraction from wheat in
      human leukocyte antigen-DQ8 transgenic mice (DQ8 mice) treated with indomethacin,
      an inhibitor of cyclooxygenases (COXs). After 10 days of treatment, mice showed a
      significant reduction of villus height, increased crypt depth, increased number
      of lamina propria-activated macrophages, and high basal interferon-gamma
      secretion in mesenteric lymph nodes, all of which were specifically related to
      gliadin intake, whereas the albumin/globulin fraction of wheat was unable to
      induce similar changes. Cotreatment with NS-398, a specific inhibitor of COX-2,
      also induced the intestinal lesion. Enteropathy onset was further characterized
      by high levels of oxidative stress markers, similar to CD. Biochemical assessment
      of the small intestine revealed the specific activation of matrix
      metalloproteinases 2 and 9, high caspase-3 activity, and a significant increase
      of tissue transglutaminase protein levels associated with the intestinal lesion.
      Notably, after 30 days of treatment, enteropathic mice developed serum antibodies
      toward gliadin (IgA) and tissue transglutaminase (IgG). We concluded that gliadin
      intake in combination with COX inhibition caused a basal inflammatory status and
      an oxidative stress condition in the small intestine of DQ8 mice, thus triggering
      the mucosal lesion and, subsequently, an antigen-specific immunity. 

PMID- 24924748
TI  - Hypersensitivity to acid is associated with impaired esophageal mucosal integrity
      in patients with gastroesophageal reflux disease with and without esophagitis.
AB  - Increased esophageal sensitivity and impaired mucosal integrity have both been
      described in patients with gastroesophageal reflux disease, but the relationship
      between hypersensitivity and mucosal integrity is unclear. The aim of the present
      study was to investigate acid sensitivity in patients with erosive and nonerosive
      reflux disease and control subjects to determine the relation with functional
      esophageal mucosal integrity changes as well as to investigate cellular
      mechanisms of impaired mucosal integrity in these patients. In this prospective
      experimental study, 12 patients with nonerosive reflux disease, 12 patients with
      esophagitis grade A or B, and 11 healthy control subjects underwent an acid
      perfusion test and upper endoscopy. Mucosal integrity was measured during
      endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were
      analyzed in Ussing chambers for transepithelial electrical resistance,
      transepithelial permeability and gene expression of tight junction proteins and
      filaggrin. Patients with nonerosive reflux disease and esophagitis were more
      sensitive to acid perfusion compared with control subjects, having a shorter time
      to perception of heartburn and higher perceived intensity of heartburn. In reflux
      patients, enhanced acid sensitivity was associated with impairment of in vivo and
      vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired
      in patients with esophagitis, displaying higher transepithelial permeability and
      lower extracellular impedance. Although no significant differences in the
      expression of tight junction proteins were found in biopsies among patient
      groups, mucosal integrity parameters in reflux patients correlated negatively
      with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced
      in patients with gastroesophageal reflux disease, irrespective of the presence of
      erosions, and is associated with impaired esophageal mucosal integrity. Mucosal
      integrity of the esophagus is associated with the expression of filaggrin. 

PMID- 24924749
TI  - Dysregulation of hepatic zinc transporters in a mouse model of alcoholic liver
      disease.
AB  - Zinc deficiency is a consistent phenomenon observed in patients with alcoholic
      liver disease, but the mechanisms have not been well defined. The objective of
      this study was to determine if alcohol alters hepatic zinc transporters in
      association with reduction of hepatic zinc levels and if oxidative stress
      mediates the alterations of zinc transporters. C57BL/6 mice were pair-fed with
      the Lieber-DeCarli control or ethanol diets for 2, 4, or 8 wk. Chronic alcohol
      exposure reduced hepatic zinc levels, but increased plasma and urine zinc levels,
      at all time points. Hepatic zinc finger proteins, peroxisome proliferator
      activated receptor-alpha (PPAR-alpha) and hepatocyte nuclear factor 4alpha (HNF
      4alpha), were downregulated in ethanol-fed mice. Four hepatic zinc transporter
      proteins showed significant alterations in ethanol-fed mice compared with the
      controls. ZIP5 and ZIP14 proteins were downregulated, while ZIP7 and ZnT7
      proteins were upregulated, by ethanol exposure at all time points.
      Immunohistochemical staining demonstrated that chronic ethanol exposure
      upregulated cytochrome P-450 2E1 and caused 4-hydroxynonenal accumulation in the
      liver. For the in vitro study, murine FL-83B hepatocytes were treated with 5 MUM
      4-hydroxynonenal or 100 MUM hydrogen peroxide for 72 h. The results from in vitro
      studies demonstrated that 4-hydroxynonenal treatment altered ZIP5 and ZIP7
      protein abundance, and hydrogen peroxide treatment changed ZIP7, ZIP14, and ZnT7
      protein abundance. These results suggest that chronic ethanol exposure alters
      hepatic zinc transporters via oxidative stress, which might account for ethanol
      induced hepatic zinc deficiency. 

PMID- 24924750
TI  - Different oral sensitivities to and sensations of short-, medium-, and long-chain
      fatty acids in humans.
AB  - Fatty acids that vary in chain length and degree of unsaturation have different
      effects on metabolism and human health. As evidence for a "taste" of
      nonesterified fatty acids (NEFA) accumulates, it may be hypothesized that fatty
      acid structures will also influence oral sensations. The present study examined
      oral sensitivity to caproic (C6), lauric (C12), and oleic (C18:1) acids over
      repeated visits. Analyses were also conducted on textural properties of NEFA
      emulsions and blank solutions. Oral thresholds for caproic acid were lower
      compared with oleic acid. Lauric acid thresholds were intermediate but not
      significantly different from either, likely due to lingering irritating
      sensations that prevented accurate discrimination. From particle size analysis,
      larger droplets were observed in blank solutions when mineral oil was used,
      leading to instability of the emulsion, which was not observed when emulsions
      contained NEFA or when mineral oil was removed from the blank. Rheological data
      showed no differences in viscosity among samples except for a slightly higher
      viscosity with oleic acid concentrations above 58 mM. Thus, texture was unlikely
      to be the property used to distinguish between the samples. Differences in oral
      detection and sensation of caproic, lauric, and oleic acids may be due to
      different properties of the fatty acid alkyl chains. 

PMID- 24924751
TI  - Predictive value of urinary and serum biomarkers in young children with febrile
      urinary tract infections.
AB  - BACKGROUND: Early predictive biomarkers for the diagnosis and management of
      febrile urinary tract infections (UTIs) can be valuable diagnostic tools in
      children. METHODS: The study cohort comprised 73 pediatric patients with febrile
      UTIs [46 with acute pyelonephritis (APN) and 27 with lower UTIs] and 56 healthy
      children. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney
      injury molecule-1 (uKIM-1) levels and serum cystatin C (sCysC) levels were
      measured. RESULTS: The uNGAL/creatinine (Cr) and uKIM-1/Cr levels were higher in
      the UTI group than in the controls (P < 0.05). uNGAL/Cr and sCysC levels were
      higher in patients with APN than in those with lower UTIs (P < 0.05). uNGAL/Cr
      levels in both the APN and UTI groups decreased following the administration of
      antibiotics compared to those before treatment (P < 0.05). The uNGAL/Cr level was
      correlated with serum levels of white blood cells, C-reactive protein, CysC and
      with uKIM-1/Cr (P < 0.05). uKIM-1/Cr was also correlated with sCysC (P < 0.05).
      Receiver operating curve analyses showed good diagnostic profiles of uNGAL/Cr and
      uKIM-1/Cr for identifying UTIs [area under the curve (AUC) 0.9 and 0.66,
      respectively) and of uNGAL/Cr and sCysC for predicting APN (AUC 0.78 and 0.72,
      respectively). CONCLUSIONS: Our results suggest that uNGAL, uKIM-1 and sCysC
      levels may be useful for predicting and managing febrile UTIs in children.

PMID- 24924756
TI  - The 7th World Congress on Itch.
AB  - All aspects of the field of itch, from basic science to quality of life to
      therapeutics, are moving rapidly. Attendees are already looking forward to the
      next congress in Nara, Japan, in the fall of 2015.

PMID- 24924752
TI  - Eculizumab treatment for rescue of renal function in IgA nephropathy.
AB  - BACKGROUND: Immunoglobulin A (IgA) nephropathy is a chronic glomerulonephritis
      with excessive glomerular deposition of IgA1, C3 and C5b-9, which may lead to
      renal failure. CASE DIAGNOSIS/TREATMENT: We describe the clinical course of an
      adolescent with rapidly progressive disease leading to renal failure in spite of
      immunosuppressive treatment. Due to refractory disease the patient was treated
      with eculizumab (anti-C5) for 3 months in an attempt to rescue renal function.
      Treatment led to clinical improvement with stabilization of the glomerular
      filtration rate and reduced proteinuria. Discontinuation of treatment led to a
      rapid deterioration of renal function. This was followed by a single dose of
      eculizumab, which again reduced creatinine levels temporarily. CONCLUSIONS: Early
      initiation of eculizumab therapy in patients with progressive IgA nephropathy may
      have a beneficial effect by blocking complement-mediated renal inflammation.

PMID- 24924757
TI  - RNA-seq permits a closer look at normal skin and psoriasis gene networks.
AB  - Psoriasis is a chronic inflammatory skin disease driven by aberrant signals from
      the immune system. In this issue, Li et al. present the first large RNA-seq
      analysis of gene expression in normal skin and psoriasis lesions, providing a
      more comprehensive view of mRNA expression than earlier microarray studies. This
      study's size enables gene co-expression analysis, a method illustrating which
      pathways are altered by the presence of disease. 

PMID- 24924758
TI  - An unexpected role: UVA-induced release of nitric oxide from skin may have
      unexpected health benefits.
AB  - UVR has deleterious and beneficial effects on human health. In this issue, Liu et
      al. (2014) show that UVA decreases blood pressure and increases blood flow and
      heart rate in humans, which is beneficial to the cardiovascular system. This is
      likely mediated by UVA causing release of nitric oxide (NO) from skin stores.
      This mediator may have additional effects on human health. 

PMID- 24924759
TI  - Opening a niche for therapy: local lymphodepletion helps the immune system to
      fight melanoma.
AB  - In this issue, Fujiwara et al. report that local ablation of CD4+ T cells in a
      murine B16 melanoma model, together with concomitant activation of the immune
      system by OX40L, leads to complete rejection of the melanomas. Rejection was
      driven mainly by CD8+ T cells, which infiltrated the melanomas and secreted
      sizeable amounts of IFN-gamma. However, CD8+ T-cell infiltration also caused the
      recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs).
      Although these cells did not prevent the rejection of the melanomas, in clinical
      settings the long-term repopulation of tumors by MDSCs may counteract successful
      treatment. Thus, local ablation of CD4+ leukocytes may improve anti-melanoma
      therapies in humans, but at the same time MDSC levels in the tumor cells have to
      be kept in check to ensure treatment success.

PMID- 24924760
TI  - Plasmacytoid dendritic cells in melanoma: can we revert bad into good?
AB  - Tumor-infiltrating plasmacytoid dendritic cells (pDCs) promote an
      immunosuppressive milieu that drives tumor growth in melanoma. This phenomenon
      typically results from the lack of appropriate pDC activation signals in the
      tumor microenvironment, but it is also actively controlled by tumor cells, which
      have evolved strategies to inhibit type I IFN production by pDCs. In this issue,
      Camisaschi et al. identify a new mechanism in which tumors avoid type I IFN
      production by triggering LAG-3-dependent activation of pDCs. Combination
      therapies that restore pDC functionality and trigger innate activation to produce
      type I IFN should be envisaged to induce effective antitumor immunity. 

PMID- 24924761
TI  - Endoplasmic reticulum calcium, stress, and cell-to-cell adhesion.
AB  - Darier's disease (DD) is caused by mutations in the endoplasmic reticulum (ER)
      Ca2+ ATPase ATP2A2 (protein SERCA2). Current treatment modalities are ineffective
      for many patients. This report shows that impaired SERCA2 function, both in DD
      keratinocytes and in normal keratinocytes treated with the SERCA2-inhibitor
      thapsigargin, depletes ER Ca2+ stores, leading to constitutive ER stress and
      increased sensitivity to ER stressors. ER stress, in turn, leads to abnormal cell
      to-cell adhesion via impaired redistribution of desmoplakin, desmoglein 3,
      desmocollin 3, and E-cadherin to the plasma membrane. This report illustrates how
      ER Ca2+ depletion and the resulting ER stress are central to the pathogenesis of
      the disease. Additionally, the authors introduce a possible new therapeutic
      agent, miglustat.

PMID- 24924762
TI  - Rethinking the potential roles of mast cells in skin wound healing and bleomycin
      induced skin fibrosis.
AB  - Skin wound healing and bleomycin-induced skin fibrosis are thought to reflect
      complex interactions among diverse cell types. Several lines of evidence have
      implicated mast cells in these tissue responses. However, data from Willenborg et
      al. (this issue) and from three other groups suggest that, in at least these
      examples of cutaneous tissue remodeling, mast cells may not have nonredundant
      roles. 

PMID- 24924764
TI  - JID VisualDx quiz: July 2014. Graft-versus-host disease.

PMID- 24924765
TI  - Transgenic mouse technology in skin biology: inducible gene knockout in mice.

PMID- 24924766
TI  - Cells to surgery quiz: July 2014. Hypertrophic scar.

PMID- 24924767
TI  - Maternal Eomesodermin regulates zygotic nodal gene expression for mesendoderm
      induction in zebrafish embryos.
AB  - Development of animal embryos before zygotic genome activation at the midblastula
      transition (MBT) is essentially supported by egg-derived maternal products. Nodal
      proteins are crucial signals for mesoderm and endoderm induction after the MBT.
      It remains unclear which maternal factors activate zygotic expression of nodal
      genes in the ventrolateral blastodermal margin of the zebrafish blastulas. In
      this study, we show that loss of maternal Eomesodermin a (Eomesa), a T-box
      transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2
      as well as mesodermal and endodermal markers, indicating an involvement in
      mesendoderm induction. Maternal Eomesa is also required for timely zygotic
      expression of the transcription factor gene mxtx2, a regulator of nodal gene
      expression. Eomesa directly binds to the Eomes-binding sites in the promoter or
      enhancer of ndr1, ndr2, and mxtx2 to activate their transcription. Furthermore,
      human and mouse Nodal genes are also regulated by Eomes. Transfection of
      zebrafish eomesa into murine embryonic stem cells promotes mesendodermal
      differentiation with constant higher levels of endogenous Nodal expression,
      suggesting a conserved function of Eomes. Taken together, our findings reveal a
      conserved role of maternal T-box transcription factors in regulating nodal gene
      expression and mesendoderm induction in vertebrate embryos. 

PMID- 24924768
TI  - Group II metal complexes of the germylidendiide dianion radical and germylidenide
      anion.
AB  - The two-electron reduction of a Group 14-element(I) complex [RE?] (E=Ge,
      R=supporting ligand) to form a novel low-valent dianion radical with the
      composition [RE:](2-) is reported. The reaction of [LGeCl] (1, L=2,6
      (CH=NAr)2C6H3, Ar=2,6-iPr2C6H3) with excess calcium in THF at room temperature
      afforded the germylidenediide dianion radical complex [LGe](2-)?Ca(THF)3(2+) (2).
      The reaction proceeds through the formation of the germanium(I) radical [LGe?],
      which then undergoes a two-electron reduction with calcium to form 2. EPR
      spectroscopy, X-ray crystallography, and theoretical studies show that the
      germanium center in 2 has two lone pairs of electrons and the radical is
      delocalized over the germanium-containing heterocycle. In contrast, the magnesium
      derivative of the germylidendiide dianion radical is unstable and undergoes
      dimerization with concurrent dearomatization to form the germylidenide anion
      complex [C6H3-2-{C(H)=NAr}Ge-Mg-6-{C(H)-NAr}]2 (3).

PMID- 24924769
TI  - Osmium density challenge.

PMID- 24924770
TI  - Solution to the absinthe challenge.

PMID- 24924771
TI  - Conventional hypoglycaemic agents and the risk of lung cancer in patients with
      diabetes: a meta-analysis.
AB  - BACKGROUND: Accumulating evidence suggests that hypoglycaemic agents influence
      lung cancer risk in patients with diabetes. It remains to be fully elucidated
      whether conventional hypoglycaemic agents (metformin, sulfonylureas,
      thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients
      with diabetes. METHODS: We performed a meta-analysis using EMBASE, MEDLINE and
      Web of Science to search randomised controlled trials (RCTs), cohort studies, and
      case-control studies published up to October 2013 that assessed the effects of
      metformin, sulfonylurea, TZDs or insulin on lung cancer risk in subjects with
      diabetes. Fixed and random effects meta-analysis models were used, and the effect
      size was expressed as a summary odds ratio (OR) with 95% confidence intervals
      (CI). The Grades of Research, Assessment, Development and Evaluation (GRADE)
      approach was applied to define the quality of the evidence. RESULTS: Analysis of
      15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that
      metformin use was associated with a 15% reduction in risk of lung cancer (OR
      0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of
      smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06). Moreover, sulfonylurea
      or TZDs use was not associated with increased or decreased lung cancer risk,
      respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02).
      Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35).
      However, all data from RCTs failed to demonstrate a statistically significant
      effect. CONCLUSIONS: This analysis demonstrated that metformin use may reduce
      lung cancer risk in patients with diabetes but not in a smoking-adjusted subgroup
      and that insulin use may be associated with an increased lung cancer risk in
      subjects with diabetes.

PMID- 24924772
TI  - Quality of 186 child brain spectra using motion and B0 shim navigated single
      voxel spectroscopy.
AB  - PURPOSE: To evaluate B0 shim and motion navigated single voxel spectroscopy in
      children. Assess the repeatability of metabolite concentrations in three regions:
      medial frontal grey matter, peritrigonal white matter, and basal ganglia.
      Determine the extent of intra- and interacquisition movement in this population.
      METHODS: Linewidth and signal to noise ratio were calculated to assess spectral
      quality of 186 spectra at 3 Tesla. Repeatability was assessed on 31 repeat scans.
      Navigator images were used to assess localization errors, while navigator motion
      and shim logs were used to demonstrate the efficacy of correction needed during
      the scans. RESULTS: Average linewidths +/- standard deviations of N-acetyl
      aspartate are 3.8 +/- 0.6 Hz, 4.4 +/- 0.5 Hz, and 4.7 +/- 0.8 Hz in each region,
      respectively. Scan-to-scan measurement variance in metabolite concentrations
      closely resembled the expected variance. A total of 73% and 32% of children moved
      before and during the acquisition, causing a voxel shift of more than 10% of the
      voxel volume, 1.5 mm. The predominant movement directions were sliding out of the
      coil and nodding (up-down rotation). First-order B0 corrections were significant
      (>10 MUT/m) in 18 % of acquisitions. CONCLUSION: Prospective motion and B0
      correction provides high quality repeatable spectra. The study found that most
      children moved between acquisitions and a substantial number moved during
      acquisitions.

PMID- 24924773
TI  - Association of traffic-related hazardous air pollutants and cervical dysplasia in
      an urban multiethnic population: a cross-sectional study.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is a necessary cause in the
      development of cervical cancer; however, not all women infected with HPV develop
      cervical cancer indicating that other risk factors are involved. Our objective
      was to determine the association between exposure to ambient levels of common
      traffic-related air toxics and cervical dysplasia, a precursor lesion for
      cervical cancer. METHODS: The study sample consisted of women enrolled in a Phase
      II clinical trial to evaluate diagnostic techniques for cervical disease in
      Houston, Texas. The current assessment is a secondary data analysis in which
      cases were defined as women diagnosed with cervical dysplasia, while those
      without cervical dysplasia served as controls. Residential census tract-level
      estimates of ambient benzene, diesel particulate matter (DPM), and polycyclic
      aromatic hydrocarbons (PAHs) were used to assess exposure. Census tract-level
      pollutant estimates were obtained from the United States Environmental Protection
      Agency. Multivariable logistic regression was used to estimate prevalence odds
      ratios (aOR) and 95% confidence intervals (CI) adjusted for age, race/ethnicity,
      education, smoking status, and HPV status. RESULTS: Women in the highest
      residential exposure categories for benzene and DPM had an increased prevalence
      of cervical dysplasia compared to the lowest exposure category (Benzene: aOR [95%
      CI] for high exposure = 1.97[1.07-3.62], very high exposure = 2.30[1.19-4.46].
      DPM: aOR [95% CI] for high exposure = 2.83[1.55-5.16], very high exposure =
      2.10[1.07-4.11]). Similarly, women with high residential exposure to PAHs had an
      increased prevalence of cervical dysplasia (aOR [95% CI] = 2.46[1.35-4.48]). The
      highest PAH exposure category was also positively associated with cervical
      dysplasia prevalence but was not statistically significant. Assessment of the
      combined effect of HAP exposure indicates that exposure to high levels of more
      than one HAP is positively associated with cervical dysplasia prevalence (p for
      trend = 0.004). CONCLUSIONS: Traffic-related HAPs, such as benzene, DPM, and
      PAHs, are not as well-regulated and monitored as criteria air pollutants (e.g.,
      ozone), underscoring the need for studies evaluating the role of these toxicants
      on disease risk. Our results suggest that exposure to traffic-related air toxics
      may increase cervical dysplasia prevalence.

PMID- 24924774
TI  - Favorable prognostic impact in loss of TP53 and PIK3CA mutations after
      neoadjuvant chemotherapy in breast cancer.
AB  - We investigated the loss of somatic mutations in TP53 and PIK3CA in breast cancer
      tissue after neoadjuvant chemotherapy (NCT) and the clinical relevance of the
      observed mutation profiles. Samples were derived from three cohorts: Cohort 1
      consisting of 206 patients undergoing NCT with matched pre- and postchemotherapy
      tumor tissues; Cohort 2 consisting of 158 additional patients undergoing NCT; and
      Cohort 3, consisting of 81 patients undergoing chemotherapy with prechemotherapy
      tumor tissues. In the first cohort, somatic mutations in TP53 or PIK3CA were
      identified in 24.8% of the pre-NCT tumor samples but in only 12.1% of the post
      NCT tumor samples (P < 0.001). Patients with initial TP53 and PIK3CA mutations
      who became negative for the mutations after NCT had a higher Miller-Payne score
      (P = 0.008), improved disease-free survival, and improved overall survival than
      those with no change or the opposite change. The association of loss of mutations
      in TP53 and PIK3CA and improved survival was successfully validated in the second
      cohort. In addition, 28.4% of the tumors showed intratumoral heterogeneity of
      somatic mutations in TP53 or PIK3CA, whereas 71.6% were homogeneous, either with
      or without the mutations. Our data reveal the novel concept that chemotherapy may
      reduce mutation frequency in patients with breast cancer. Furthermore, the loss
      of somatic mutations in TP53 and PIK3CA may be translated to biomarkers for
      prognosis via further verification, which may optimize the choice of sequential
      therapy and improve patient survival.

PMID- 24924778
TI  - ASC-J9 suppresses renal cell carcinoma progression by targeting an androgen
      receptor-dependent HIF2alpha/VEGF signaling pathway.
AB  - Males have a higher incidence of renal cell carcinoma (RCC) than females, but the
      reason for this gender difference is unknown. Addressing this question, we report
      the discovery of an androgen receptor (AR)-induced HIF2alpha/VEGF signal that
      drives RCC progression. AR attenuation or augmentation in RCC cells altered their
      proliferation, migration, and invasion in multiple models in vitro and in vivo.
      Mechanistic investigations revealed that AR targeting inhibited RCC cell
      migration and invasion by modulating HIF2alpha/VEGF signals at the level of mRNA
      and protein expression. Interrupting HIF2alpha/VEGF signals with inhibitors of
      either HIF2alpha or VEGF was sufficient to suppress RCC progression. Similarly,
      the specific AR degradation enhancer ASC-J9 was sufficient to suppress AR-induced
      HIF2alpha/VEGF signaling and RCC progression in multiple models in vitro and in
      vivo. Taken together, our results revealed a novel role for AR in RCC initiation
      and progression with implications for novel therapeutic strategies.

PMID- 24924775
TI  - The early detection of pancreatic cancer: what will it take to diagnose and treat
      curable pancreatic neoplasia?
AB  - Pancreatic cancer is the deadliest of all solid malignancies. Early detection
      offers the best hope for a cure, but characteristics of this disease, such as the
      lack of early clinical symptoms, make the early detection difficult. Recent
      genetic mapping of the molecular evolution of pancreatic cancer suggests that a
      large window of opportunity exists for the early detection of pancreatic
      neoplasia, and developments in cancer genetics offer new, potentially highly
      specific approaches for screening of curable pancreatic neoplasia. We review the
      challenges of screening for early pancreatic neoplasia, as well as opportunities
      presented by incorporating molecular genetics into these efforts.

PMID- 24924779
TI  - Eckols reduce dental pulp inflammation through the ERK1/2 pathway independent of
      COX-2 inhibition.
AB  - OBJECTIVES: The aim of this study was to elucidate the role of 6-6 bieckol (EB1)
      and pholorofucofuroeckol-A (EB5) from brown seaweed marine algae (Eisenia
      bicyclis) on lipopolysaccharide (LPS)-induced inflammation in human dental pulp
      cells (HDPCs). METHODS: The cytotoxicity of EB1 and EB5 was examined by MTT assay
      on LPS-induced human dental pulp cells. Their role on expression of inflammatory,
      odontogenic, and osteogenic molecules was determined by Western blot analysis.
      The dentin mineralization was checked by alkaline phosphatase activity. RESULTS:
      The five compounds from E. bicyclis have different structure with non-cytotoxic
      in HDPCs. EB1 and EB5 showed anti-inflammatory properties and inhibited
      phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) and
      phosphorylated-c-jun N-terminal kinases (p-JNK) without any cytotoxicity. In
      particular, EB1 inhibited cyclooxygenase-2 (COX-2) and p-ERK1/2 signaling, and
      EB5 inhibited only p-ERK1/2 signaling but not COX-2. Both compounds inhibited
      nuclear factor kappa-B (NF-kappaB) translocation. Furthermore, EB1 and EB5
      increased dentinogenic and osteogenic molecules, and dentin mineralized via
      alkaline phosphatase activity (ALP) in LPS-induced HDPCs. CONCLUSIONS: This study
      elucidates that EB1 and EB5 have different types of anti-inflammatory property
      and help in dentin formation. Therefore, these compounds derived from marine
      algae of E. bicyclis may be used as selective therapeutic strategies for pulpitis
      and oral diseases.

PMID- 24924780
TI  - The WERO group stop smoking competition: main outcomes of a pre- and post- study.
AB  - BACKGROUND: One potential promising strategy for increasing smoking cessation for
      Maori (Indigenous New Zealanders) and New Zealand resident Pacific Island people
      is Quit and Win competitions. The current uncontrolled pre and post study, WERO
      (WERO in Maori language means challenge), differs from previous studies in that
      it aims to investigate if a stop smoking contest, using both within team support,
      external support from a team coach and cessation experts, and technology, would
      be effective in prompting and sustaining quitting. METHOD: Fifteen teams,
      recruited from urban Maori, rural Maori and urban Pacific communities, competed
      to win a NZ$5000 (about ? 3,000, L 2600) prize for a charity or community group
      of their choice. People were eligible if they were aged 18 years and over and
      identified as smokers. Smoking status was biochemically validated at the start
      and end of the 3 month competition. At 3-months post competition self-reported
      smoking status was collected. RESULTS: Fourteen teams with 10 contestants and one
      team with eight contestants were recruited. At the end of the competition the
      biochemically verified quit rate was 36%. The 6 months self-reported quit rate
      was 26%. The Pacific and rural Maori teams had high end of competition and 6
      months follow-up quit rates (46% and 44%, and 36% and 29%). CONCLUSION: WERO
      appeared to be successful in prompting quitting among high smoking prevalence
      groups. WERO combined several promising strategies for supporting cessation: peer
      support, cessation provider support, incentives, competition and interactive
      internet and mobile tools. Though designed for Maori and Pacific people, WERO
      could potentially be effective for other family- and community-centred cultures.

PMID- 24924781
TI  - The yeast protein interaction network has a capacity for self-organization.
AB  - The organization of the cellular interior gives rise to properties including
      metabolic channeling and micro-compartmentalization of signaling. Here, we use a
      lattice model of molecular crowding, together with literature-derived protein
      interactions and abundances, to describe the molecular organization and
      stoichiometry of local cellular regions, showing that physical protein-protein
      interactions induce emergent structures not seen when random interaction networks
      are modeled. Specifically, we find that the lattices give rise to micro-groups of
      enzymes on the surfaces of protein clusters. These arrangements of proteins are
      also robust to protein overexpression, while still showing evidence for
      expression tuning. Our results indicate that some of the complex organization of
      the cell may derive from simple rules of molecular aggregation and interaction. 

PMID- 24924782
TI  - High altitude cachexia: adaptation instead of deterioration? (Comment on DOI
      10.1002/bies.201400042).

PMID- 24924783
TI  - Temporal course of streptozotocin-induced diabetic polyneuropathy in rats.
AB  - The temporal course of diabetic polyneuropathy in a rat model plays a critical
      role in studies on diabetic polyneuropathy treatment. In this study, the temporal
      course of neuropathic symptoms was investigated in diabetic rats induced by
      streptozotocin and evaluated by nerve conduction velocity and behavioral assays,
      including the von Frey test for mechanical allodynia and the hot plate test for
      hyperalgesia. The results revealed that both mechanical allodynia and heat
      hyperalgesia started on the 2nd week, while nerve conduction velocity
      significantly decreased from the 1st week. In addition, the severity of allodynia
      did not change after the 3rd week. Hyperalgesia and nerve conduction velocity
      progressively aggravated even to the 8th week. Transmission electron microscopy
      showed that loss of unmyelinated axons, loosening of the myelin structure, and
      thickening of the perineurium layer were visible from the 4th week and worsened
      on the 8th week. Differences in the temporal course of neuropathic symptoms are
      discussed. 

PMID- 24924784
TI  - Volcanic conduit migration over a basement landslide at Mount Etna (Italy).
AB  - The flanks of volcanoes may slide in response to the loading of the edifice on a
      weak basement, magma push, and/or to tectonic stress. However, examples of
      stratovolcanoes emplaced on active landslides are lacking and the possible
      effects on the volcano dynamics unknown. Here, we use aeromagnetic data to
      construct a three-dimensional model of the clay-rich basement of Etna volcano
      (Italy). We provide evidence for a large stratovolcano growing on a pre-existing
      basement landslide and show that the eastern Etna flank, which slides toward the
      sea irrespective of volcanic activity, moves coherently with the underlying
      landslide. The filling of the landslide depression by lava flows through time
      allows the formation of a stiffness barrier, which is responsible for the long
      term migration of the magma pathways from the coast to the present-day Etna
      summit. These unexpected results provide a new interpretation clue on the causes
      of the volcanic instability processes and of the mechanisms of deflection and
      migration of volcanic conduits. 

PMID- 24924785
TI  - Propagation of thickness-twist waves in elastic plates with periodically varying
      thickness and phononic crystals.
AB  - We study the propagation of thickness-twist (TT) waves in a crystal plate of AT
      cut quartz with periodically varying, piecewise constant thickness. The scalar
      differential equation by Tiersten and Smythe is employed. The problem is found to
      be mathematically equivalent to the motion of an electron in a periodic potential
      field governed by Schrodinger's equation. An analytical solution is obtained.
      Numerical results show that the eigenvalue (frequency) spectrum of the waves has
      a band structure with allowed and forbidden bands. Therefore, for TT waves,
      plates with periodically varying thickness can be considered as phononic
      crystals. The effects of various parameters on the frequency spectrum are
      examined. 

PMID- 24924786
TI  - Sputtered ZnO film on aluminium foils for flexible ultrasonic transducers.
AB  - Nanocrystalline ZnO films with both C-axis vertical grown and inclined angled
      grown were sputter-deposited onto aluminium foils (50 MUm thick) and
      characterised for using as flexible ultrasonic transducers. As-deposited C-axis
      grown ZnO films were annealed at different temperatures up to 600  degrees C to
      enhance film crystallinity and reduce film stress. The C-axis grown ZnO film on
      the Al foil were bonded onto steel plates, and the pulse-echo tests verified a
      good performance (with dominant longitudinal waves) of the ultrasonic transducers
      made from both as-deposited and post-annealed films. Inclined angled ZnO films on
      the Al foil glued onto steel plates generated mixed shear and longitudinal waves
      in the pulse-echo test.

PMID- 24924787
TI  - Timeout induced by differential-reinforcement-of-low-rate schedules.
AB  - Three rats pressed a lever for food on differential-reinforcement-of-low-rate
      (DRL) schedules ranging from 16 s to 96 s. During DRL performance, a response to
      a second lever turned off chamber illumination and produced a timeout period
      during which food could not be obtained. During timeout periods, a response to
      the second lever reinstated the DRL schedule and associated chamber illumination.
      The percentage of session time spent in timeout periods increased as the DRL
      schedule was lengthened and decreased when the schedule was shortened. Changes in
      timeout percentage were primarily due to changes in the mean time per timeout
      rather than to changes in the rate of initiation of timeout periods. Extinction
      increased the timeout percentage. Elimination of the timeout contingency
      decreased the response rate to the timeout lever, but did not systematically
      affect DRL lever pressing. The rate of reinforcement appeared to be a primary
      determinant of the percent of session time spent in timeout periods. 

PMID- 24924788
TI  - Social isolation increases social display after priming in Betta splendens but
      decreases aggressive readiness.
AB  - We socially isolated adult, male Siamese fighting fish for 0 to 7 weeks but
      avoided sensory deprivation, and then measured aggressive display as the fish
      responded to a series of novel models. Isolates displayed much more strongly than
      non-isolates to the last model of the series, and display intensity became
      monotonically stronger with longer social isolation. By contrast, display to the
      first model seen after isolation was weaker the longer the social isolation. A
      second experiment compared responses of fish after three weeks during which
      controls displayed to a conspecific for two minutes every two days, while
      isolates saw a complex visual stimulus which did not release display. Again,
      isolates had depressed display readiness, but higher display rates once they were
      primed. This result supports the hypothesis that social isolation has two effects
      on aggressive display in Betta, causing decreasing readiness to display, but
      leading to greater display rates once fish are 'primed'. We discuss two models
      which predict these phenomena, and show that one of them suggests a new
      understanding of the function of motivational increases when aggression is
      'dammed up'. Methodological issues relevant for examining the rodent behavior
      literature in the light of the new model are discussed. 

PMID- 24924789
TI  - Predation in caves: the effects of prey immobility and darkness on the foraging
      behaviour of two salamanders, Euproctus asper and Proteus anguinus.
AB  - The behavioural responses of the blind cave salamander Proteus anguinus and the
      Pyrenean salamander Euproctus asper (a facultative cave dweller) to living and
      dead chironomids offered in light or in darkness were studied experimentally.
      Both species were able to detect and locate single prey items positioned at
      distances of 30 cm. Proteus responded to dead prey in light faster and captured
      live prey in darkness earlier than E. asper. E. asper captured live prey in light
      earlier than in darkness. Proteus is well equipped to search for non-visual
      information and used an active, mechanically and chemically guided approach in
      all experiments. E. asper showed a more directed, visually dominated approach
      behaviour with live chironomids in light, but used an active, widely foraging
      mode with live prey in darkness and dead prey in light. E. asper may forage
      successfully both in epigean and hypogean habitats. 

PMID- 24924790
TI  - Abdomen stroking behaviour and its possible functions in Polistes dominulus
      (christ) (hymenoptera, vespidae).
AB  - The behaviour of stroking the abdomen over the nest surface has previously been
      described in females of only a few Polistes wasp species, and was considered to
      be associated with pheromonal release. This study examines abdomen stroking in
      solitary and multiple female laboratory colonies of Polistes dominulus during the
      pre-emergence period. In multiple female colonies stroking behaviour is related
      to hierarchy: alpha females stroking more than subordinates. However, after
      removal of the dominant female the subordinate increases her stroking rate.
      Solitary females also stroke but, unlike alpha females, they do so less during
      the egg-stage than in subsequent stages of the colonial cycle. It is hypothesized
      that abdomen stroking cues the immature brood as to which adult female is the
      dominant individual; this could lead to competition between females on the same
      nest. This function is also discussed in the context of intra- and inter-specific
      Polistes parasites, where the behaviour is particularly evident. 

PMID- 24924791
TI  - Conspecific intruders influence pair formation in a monogamous fish.
AB  - In aquaria, monogamous Texas cichlid fish (Cichlasoma cyanoguttatum) formed
      reproductive pairs significantly more often when another conspecific male (termed
      'intruder') was visible behind a plexiglass partition. Without an intruder
      present, males often violently attacked and injured the female. Larger females,
      although attacked more frequently, were less prone to severe injuries. Pairs did
      not form when females were larger than males, irrespective of the presence of an
      intruder. 

PMID- 24924792
TI  - Reorganization of cues and path organisation in dogs.
AB  - Dogs were submitted to a free search for food which was distributed in six
      feeding points situated on a circle. In the first part of the experiment they
      were able to reorganize information collected on radial paths leading from the
      center to the feeding points in order to invent new routes between these points.
      There were considerable differences in the degree of stereotypy and variability
      of visit sequences between the six dogs used in this experiment, with
      overtraining tending to induce locomotory habits in dogs using varied sequences.
      These habits were not however disconnected from the representational processes,
      since dogs used a variety of sequences without making any error when the starting
      conditions were made to vary. In the second part of the experiment, our aim was
      to analyse whether, without taking environmental cues into account, the dogs were
      able to learn that stable geometrical relationships existed among three food
      points and between these points and the starting place. The dogs' behavior showed
      that they were able to learn something about the experimental rule. However it is
      not clear if they have detected the geometrical relationships among baited food
      points, or the simultaneous presence of food at specific points, or both. 

PMID- 24924793
TI  - Stimuli inducing the regurgitation of the workers of Lasius flavus (formicidae)
      upon the myrmecophilous beetle Claviger testaceus (pselaphidae).
AB  - Experiments have shown that, contrary to what has been stated in the literature,
      the limited antennal movements of the myrmecophilous beetle, Claviger testaceus,
      are not required for inducing the workers of its host, Lasius flavus, to
      regurgitate food. Experiments have also shown that the regurgitations are
      released by the secretions of the Claviger's labral (cephalic) and Wasmann
      (abdominal) glands. These secretions contain a regurgitation allomone and are
      taken up by the ants when they lick the beetle's mouthparts or trichomes. The
      allomone is not present in the myrmecophile's hemolymph. 

PMID- 24924794
TI  - Behavioural responses to single and repeated restraint in male and female rats.
AB  - The effects of single and repeated restraint (RT) on non-social behaviour were
      investigated in male and female rats. The animals underwent either 15-min or 30
      min single RT (Experiment 1), or daily 30-min RT for 7 days (Experiment 2).
      Behavioural parameters recorded included locomotion and exploration in the hole
      board and anxiety in the elevated plus-maze. Effects of RT depended on sex,
      parameter and schedule of RT administration. After 15-min single RT, anxiety
      increased and exploration decreased in males; after 30-min single RT, motor
      activity decreased in both sexes, and anxiety increased in females. After
      repeated RT, exploration and anxiety were unmodified in males, indicating
      habituation. Residual emotionality was suggested by increased time spent self
      grooming and preferential locomotion in the peripheral squares of the open field.
      In females, habituation was observed in locomotion and anxiety. Interestingly,
      parameters which did not habituate suggested decreased emotionality: exploration
      increased, and ambulation in central squares was preferred to peripheral
      locomotion. Caution is needed in taking these marginal modifications of female
      behaviour as facilitatory effects, possibly concurring to increase individual
      fitness. In summary, both single and repeated RT caused less behavioural deficits
      in females than in males. Effects on exploration were sex-dependent, and
      different after single and repeated stress. Locomotion in peripheral vs. central
      squares, and self-grooming, were also affected by RT sex-dependently, but with
      similar effects after single and repeated stress. In contrast with the above
      mentioned items, modifications of anxiety appeared uninfluenced by sex. 

PMID- 24924795
TI  - Social affinities as the basis of the social organization of a Pyrenean chamois
      (Rupicapra pyrenaica) population in an open mountain range.
AB  - The tendencies of different age and sex classes to flock with each other were
      analysed in a Pyrenean chamois (Rupicapra pyrenaica) population of southern
      France, on the basis of the distribution of groups into various types and sizes.
      The strongest inter-attraction is undoubtedly that existing between adult females
      and kids, even if each age and sex class also associates easily with itself.
      Yearlings globally seem to have lower affinities with adults of both sexes than
      with their own class, but, in any case, the lowest inter-attraction is between
      adult females and males. These social affinities, varying in detail, actually
      remain roughly the same through the seasons. However, the most important point is
      that they seem sufficient to explain the main characteristics of the social
      structure of the studied Pyrenean chamois population in open habitat; it does not
      seem necessary to hypothesize complicated individual 'choices' or 'preferences'
      to explain it. This allows for a systemic approach of such a population,
      considering individuals as simple elements, which permits us to understand the
      basis of sociality and to explain inter-populational differences. 

PMID- 24924796
TI  - Polydopamine--an organocatalyst rather than an innocent polymer.
AB  - Polydopamine (PDA) is easily available by oxidation of dopamine and is widely
      used for persistent coatings of various materials. It is hitherto considered to
      be inert in many interesting biomedical and other applications. Results presented
      here, reveal an unexpected behavior of polydopamine as an organocatalyst in
      direct aldol reactions under mild conditions. Evidence was found for dual
      catalysis making use of amino and phenolic hydroxy groups found in PDA. Thus
      scientists must be aware that PDA is not an innocent polymer and can cause
      unwanted side effects in important applications, such as in biomedicine or as
      supports in catalysis. 

PMID- 24924797
TI  - Multiplex real-time PCR assay for detection of pathogenic Vibrio parahaemolyticus
      strains.
AB  - Foodborne disease caused by pathogenic Vibrio parahaemolyticus has become a
      serious public health problem in many countries. Rapid diagnosis and the
      identification of pathogenic V. parahaemolyticus are very important in the
      context of public health. In this study, an EvaGreen-based multiplex real-time
      PCR assay was established for the detection of pathogenic V. parahaemolyticus.
      This assay targeted three genetic markers of V. parahaemolyticus (species
      specific gene toxR and virulence genes tdh and trh). The assay could
      unambiguously identify pathogenic V. parahaemolyticus with a minimum detection
      limit of 1.4 pg genomic DNA per reaction (concentration giving a positive
      multiplex real-time PCR result in 95% of samples). The specificity of the assay
      was evaluated using 72 strains of V. parahaemolyticus and other bacteria. A
      validation of the assay with clinical samples confirmed its sensitivity and
      specificity. Our data suggest the newly established multiplex real-time PCR assay
      is practical, cost-effective, specific, sensitive and capable of high-throughput
      detection of pathogenic V. parahaemolyticus.

PMID- 24924798
TI  - Patient-reported genitourinary dysfunction after laparoscopic and open rectal
      cancer surgery in a randomized trial (COLOR II).
AB  - BACKGROUND: This article reports on patient-reported sexual dysfunction and
      micturition symptoms following a randomized trial of laparoscopic and open
      surgery for rectal cancer. METHODS: Patients in the COLOR II randomized trial,
      comparing laparoscopic and open surgery for rectal cancer, completed the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-CR38 questionnaire
      before surgery, and after 4 weeks, 6, 12 and 24 months. Adjusted mean differences
      on a 100-point scale were calculated using changes from baseline value at the
      various time points in the domains of sexual functioning, sexual enjoyment, male
      and female sexual problems, and micturition symptoms. RESULTS: Of 617 randomized
      patients, 385 completed this phase of the trial. Their mean age was 67.1 years.
      Surgery caused an anticipated reduction in genitourinary function after 4 weeks,
      with no significant differences between laparoscopic and open approaches. An
      improvement in sexual dysfunction was seen in the first year, but some male
      sexual problems persisted. Before operation 64.5 per cent of men in the
      laparoscopic group and 55.6 per cent in the open group reported some degree of
      erectile dysfunction. This increased to 81.1 and 80.5 per cent respectively 4
      weeks after surgery, and 76.3 versus 75.5 per cent at 12 months, with no
      significant differences between groups. Micturition symptoms were less affected
      than sexual function and gradually improved to preoperative levels by 6 months.
      Adjusting for confounders, including radiotherapy, did not change these results.
      CONCLUSION: Sexual dysfunction is common in patients with rectal cancer, and
      treatment (including surgery) increases the proportion of patients affected. A
      laparoscopic approach does not change this. REGISTRATION NUMBER: NCT00297791
      (http://www.clinicaltrials.gov).

PMID- 24924799
TI  - Hippocampal atrophy in major depression: a function of childhood maltreatment
      rather than diagnosis?
AB  - Reduced hippocampal volumes are probably the most frequently reported structural
      neuroimaging finding associated with major depressive disorder (MDD). However, it
      remains unclear whether altered hippocampal structure represents a risk factor
      for or a consequence of MDD. Reduced hippocampal volumes were consistently
      reported in subjects affected by childhood maltreatment. As the prevalence of
      childhood maltreatment is highly elevated in MDD populations, previous
      morphometric findings regarding hippocampal atrophy in MDD therefore might have
      been confounded by maltreatment experiences. The aim of this study was to
      differentiate the impact of childhood maltreatment from the influence of MDD
      diagnosis on hippocampal morphometry. Depressed patients (85) as well as 85 age-
      and sex-matched healthy controls underwent structural MRI. The Childhood Trauma
      Questionnaire was administered to estimate experiences of childhood maltreatment.
      Hippocampal volume and surface structure was examined by the use of two
      independent methods, automated segmentation (FSL-FIRST) and voxel-based
      morphometry (VBM8). In line with existing studies, MDD patients showed reduced
      hippocampal volumes, and childhood maltreatment was consistently associated with
      hippocampal volume loss in both, patients and healthy controls. However, no
      analysis revealed significant morphological differences between patients and
      controls if maltreatment experience was regressed out. Our results suggest that
      hippocampal alterations in MDD patients may at least partly be traced back to
      higher occurrence of early-life adverse experiences. Regarding the strong
      morphometric impact of childhood maltreatment and its distinctly elevated
      prevalence in MDD populations, this study provides an alternative explanation for
      frequently observed limbic structural abnormalities in depressed patients. 

PMID- 24924801
TI  - A tandem synthesis of 5-sulfonylimino-2-imidazolones from sulfonoketenimides and
      dialkyl azodicarboxylates.
AB  - Functionalized 5-sulfonylimino-2-imidazolones are prepared by a copper-catalyzed
      reaction of dialkyl azodicarboxylates with sulfonoketenimides, generated from
      terminal alkynes and sulfonyl azides, in good to excellent yields. 

PMID- 24924802
TI  - Rethinking vulnerability analysis and governance with emphasis on a participatory
      approach.
AB  - This article draws on vulnerability analysis as it emerged as a complement to
      classical risk analysis, and it aims at exploring its ability for nurturing risk
      and vulnerability governance actions. An analysis of the literature on
      vulnerability analysis allows us to formulate a three-fold critique: first,
      vulnerability analysis has been treated separately in the natural and the
      technological hazards fields. This separation prevents vulnerability from
      unleashing the full range of its potential, as it constrains appraisals into
      artificial categories and thus already closes down the outcomes of the analysis.
      Second, vulnerability analysis focused on assessment tools that are mainly
      quantitative, whereas qualitative appraisal is a key to assessing vulnerability
      in a comprehensive way and to informing policy making. Third, a systematic
      literature review of case studies reporting on participatory approaches to
      vulnerability analysis allows us to argue that participation has been important
      to address the above, but it remains too closed down in its approach and would
      benefit from embracing a more open, encompassing perspective. Therefore, we
      suggest rethinking vulnerability analysis as one part of a dynamic process
      between opening-up and closing-down strategies, in order to support a
      vulnerability governance framework. 

PMID- 24924800
TI  - A role beyond learning for NMDA receptors in reward-based decision-making-a
      pharmacological study using d-cycloserine.
AB  - N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in
      many forms of learning and plasticity. More recently, biophysical models,
      however, have suggested an additional role of NMDA receptors in evidence
      integration for decision-making, going beyond their role in learning. We designed
      a task to study the role of NMDA receptors in human reward-guided learning and
      decision-making. Human participants were assigned to receive either 250 mg of the
      partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27).
      Reward-guided learning and decision-making were assessed using a task in which
      participants had to integrate learnt and explicitly shown value information to
      maximize their monetary wins and minimize their losses. To tease apart the
      effects of NMDA on learning and decision-making we used simple learning models. D
      cycloserine shifted decision-making towards a more optimal integration of the
      learnt and the explicitly shown information, in the absence of a direct learning
      effect. In conclusion, our results reveal a distinct role for NMDA receptors in
      reward-guided decision-making. We discuss these findings in the context of NMDA's
      roles in neuronal super-additivity and as crucial for evidence integration for
      decisions. 

PMID- 24924803
TI  - The PXR rs7643645 polymorphism is associated with the risk of higher prostate
      specific antigen levels in prostate cancer patients.
AB  - Levels of enzymes that determine testosterone catabolism such as CYP3A4 have been
      associated with prostate cancer (PCa) risk. Although some studies have related
      CYP3A4*1B allele, a gene polymorphism that modifies CYP3A4 expression level, with
      PCa risk, others have failed, suggesting that additional genetic variants may be
      involved. Expression of CYP3A4 is largely due to the activation of Pregnane X
      Receptor (PXR). Particularly, rs2472677 and rs7643645 PXR polymorphisms modify
      CYP3A4 expression levels. To evaluate whether PXR-HNF3beta/T (rs2472677), PXR
      HNF4/G (rs7643645), and CYP3A4*1B (rs2740574) polymorphisms are associated with
      PCa a case control-study was performed. The multiple testing analysis showed that
      the PXR-HNF4/G polymorphism was associated with higher levels of prostate
      specific antigen (PSA) in patients with PCa (OR = 3.99, p = 0.03). This
      association was stronger in patients diagnosed at the age of 65 years or older
      (OR = 10.8, p = 0.006). Although the CYP3A4*1B/*1B genotype was overrepresented
      in PCa patients, no differences were observed in the frequency of this and PXR
      HNF3beta/T alleles between controls and cases. Moreover, no significant
      association was found between these polymorphisms and PSA, Gleason grade, or
      tumor lymph node metastasis. 

PMID- 24924804
TI  - Differential effects of intrastriatal 6-hydroxydopamine on cell number and
      morphology in midbrain dopaminergic subregions of the rat.
AB  - The midbrain dopaminergic perikarya are differentially affected in Parkinson's
      disease (PD). This study compared the effects of a partial unilateral
      intrastriatal 6-hydroxydopamine (6-OHDA) lesion model of PD on the number,
      morphology, and nucleolar volume of dopaminergic cells in the substantia nigra
      pars compacta (SNpc), ventral tegmental area (VTA), and retrorubral field (RRF).
      Adult, male rats (n=10) underwent unilateral intrastriatal infusion of 6-OHDA
      (12.5MUg). Lesions were verified by amphetamine-stimulated rotation 7 days post
      infusion. Rats were euthanized 14 days after treatment with 6-OHDA and brains
      were stained with a tyrosine hydroxylase-silver nucleolar (TH-AgNOR) stain.
      Dopaminergic cell number and morphology in the lesioned and intact hemispheres
      were quantified using stereological methods. The magnitude of decrease in
      planimetric volume, neuronal number, cell density, and neuronal volume resulting
      from 6-OHDA lesion differed between regions, with the SNpc exhibiting the
      greatest loss of neurons (46%), but the smallest decrease in neuronal volume
      (13%). The lesion also resulted in a decrease in nucleolar volume that was
      similar in all three regions (22-26%). These findings indicate that intrastriatal
      6-OHDA lesion differentially affects dopaminergic neurons in the SNpc, VTA, and
      RRF; however, the resulting changes in nucleolar morphology suggest a similar
      cellular response to the toxin in all three cell populations. 

PMID- 24924805
TI  - Fish oil modulates glycogen synthase kinase-3 signaling pathway in diabetes
      induced hippocampal neurons apoptosis.
AB  - Previous research has demonstrated that diabetes induces learning and memory
      deficits. However, the mechanism of memory impairment induced by diabetes is
      poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids,
      have been shown to enhance learning and memory and prevent memory deficits in
      various experimental conditions. The present study investigated the effects of
      fish oil supplementation on the neuron apoptosis in the hippocampus of
      streptozotocin (STZ)-induced diabetes rats, further explored the effect of fish
      oil on the phosphorylation of protein kinase B and glycogen synthase kinase-3
      beta. The effects of diabetes and fish oil treatment on the spatial learning and
      memory were also evaluated using the Morris Water Maze. STZ-induced diabetes
      impaired spatial learning and memory of rats, which was associated with the
      apoptosis of hippocampal neurons and oxidative stress. Fish oil administration
      ameliorated cognitive deficit, reduced oxidative stress, increased AKT
      phosphorylation, decreased GSK-3beta phosphorylation, and decreased pro-apoptotic
      molecules expression, which protected the hippocampal neurons from apoptosis in
      diabetic rats. These results suggested a potential role for fish oil as an
      adjuvant therapy for the prevention and treatment of diabetic complications. 

PMID- 24924806
TI  - CXCR-7 receptor promotes SDF-1alpha-induced migration of bone marrow mesenchymal
      stem cells in the transient cerebral ischemia/reperfusion rat hippocampus.
AB  - The stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR-4)
      axis plays an important role during stem cell recruitment. SDF-1 can also bind
      the more recently described CXCR-7 receptor, but effects of SDF-1/CXCR-7
      signaling on stem cell migrating to ischemic brain injury area are little known.
      In the present study, we investigated the effect of CXCR-7 on bone marrow
      mesenchymal stem cell (BMSC) migration toward SDF-1alpha in the cerebral
      ischemia/reperfusion (I/R) rat hippocampus. We cultured BMSCs from rats and
      characterized them using flow cytometry, immunocytochemistry, western blotting,
      and immunofluorescence to detect SDF-1alpha, CXCR-4, and CXCR-7 expression in
      third passage BMSCs (P3-BMSCs). We also prepared the model of transient cerebral
      I/R by four-vessel occlusion (4-VO), and BMSCs were transplanted into I/R rat
      brain via lateral ventricle (LV) injection (20MUl, 1*10(6)/ml). After that, we
      examined the effect of BMSCs migration in the cerebral I/R rat hippocampus
      through Transwell chamber assay. Our results show that SDF-1alpha, CXCR-4, and
      CXCR-7 were expressed in P3-BMSCs. Moreover, SDF-1alpha expression was increased
      in I/R hippocampus. At 48h after transplant, green fluorescent BrdU-BMSCs were
      observed in transplant groups, but no green fluorescent BrdU-BMSCs were seen in
      medium group. Among BMSCs transplant groups, the number of BrdU-BMSCs positive
      cell was the highest in BMSC group. Treatment with AMD3100 and/or CXCR-7
      neutralizing antibody decreased the number of BMSC migration. Collectively, these
      findings indicate that CXCR-4 and -7 receptors were co-expressed in BMSCs and
      synergistically promoted BMSC migration. The effect of CXCR-7 was stronger than
      that of CXCR-4. Moreover, BMSCs that migrated to hippocampus promoted the
      autocrine and paracrine signaling of SDF-1alpha.

PMID- 24924807
TI  - Lithium-ion transport through a tailored disordered phase on the LiNi0.5 Mn1.5 O4
      surface for high-power cathode materials.
AB  - The phase control of spinel LiNi0.5 Mn1.5 O4 was achieved through surface
      treatment that led to an enhancement of its electrochemical properties. Li(+)
      diffusion inside spinel LiNi0.5 Mn1.5 O4 could be promoted by modifying the
      surface structure of LiNi0.5 Mn1.5 O4 through phosphidation into a disordered
      phase (Fd3m) that allows facile Li(+) transport. Phosphidated LiNi0.5 Mn1.5 O4
      showed a significantly enhanced electrochemical performance, even at high rates
      exceeding 10 C, demonstrating that the improved kinetics (related to the amount
      of Mn(3+) ) can render LiNi0.5 Mn1.5 O4 competitive as a high-power cathode
      material for electric vehicles and hybrid electric vehicles. 

PMID- 24924809
TI  - Using in situ voltammetry as a tool to identify and characterize habitats of iron
      oxidizing bacteria: from fresh water wetlands to hydrothermal vent sites.
AB  - Iron-oxidizing bacteria (FeOB) likely play a large role in the biogeochemistry of
      iron, making the detection and understanding of the biogeochemical processes FeOB
      are involved in of critical importance. By deploying our in situ voltammetry
      system, we are able to measure a variety of redox species, specifically Fe(ii)
      and O2, simultaneously. This technique provides significant advantages in both
      characterizing the environments in which microaerophilic FeOB are found, and
      finding diverse conditions in which FeOB could potentially thrive. Described here
      are four environments with different salinities [one fresh groundwater seep site,
      one beach-groundwater mixing site, one hydrothermal vent site (Mid-Atlantic
      Ridge), and one estuary (Chesapeake Bay)] where in situ voltammetry was deployed,
      and where the presence of FeOB were confirmed by either culturing methods or
      molecular data. The sites varied in both O2 and Fe(ii) content with O2 ranging
      from below the 3 MUM detection limit of the electrodes at the Chesapeake Bay
      suboxic zone, to as high 150 MUM O2 at the vent site. In addition, a range of
      Fe(ii) concentrations supported FeOB communities, from 3 MUM Fe(ii) in the
      Chesapeake Bay to 300 MUM in the beach aquifer. In situ electrochemistry provides
      the means to quickly measure these redox gradients at appropriate resolution,
      making it possible in real time to detect niches likely inhabited by
      microaerophilic FeOB, then accurately sample for proof of FeOB presence and
      activity. This study demonstrates the utility of this approach while also greatly
      expanding our knowledge of FeOB habitats. 

PMID- 24924810
TI  - Assessing how reduced expression levels of the mismatch repair genes MLH1, MSH2,
      and MSH6 affect repair efficiency.
AB  - Lynch syndrome (LS), the most common familial colon cancer, is associated with
      mismatch repair (MMR) malfunction. As mutation carriers inherit one normal and
      one defected MMR gene allele, cancer risk can be considered as limited amount of
      normal MMR gene product. How reductions in different MMR gene expressions affect
      MMR capability is, however, not known. The in vitro MMR assay is a method for the
      pathogenicity assessment of MMR gene variants causing functional or expressional
      defects and thus also suitable to evaluate the effects of reduced expression of
      normal mRNA. Here, the assay was applied to quantify repair efficiencies of human
      cells retaining varying expression levels (25%/50%/75%) of the main LS
      susceptibility genes MLH1, MSH2, or MSH6. Compared with the shRNA knockdown
      control, already a 50% reduction in mRNA levels could be detected as decreased
      MMR function although without statistical significance in MLH1. In MSH2 and MLH1,
      total loss of MMR was achieved with 25% expression, whereas in MSH6 and MSH2, the
      repair capability decreased significantly already with 75% expression. Our
      results provide a preliminary indication of relative expressions required for
      wild-type function and suggest that the in vitro MMR assay could be used to
      recognize expression levels indicative of LS. 

PMID- 24924811
TI  - Allergic contact dermatitis caused by benzanthrone in a pair of trousers.

PMID- 24924812
TI  - Allergic contact dermatitis due to a surgical marker.

PMID- 24924813
TI  - Occupational allergic contact dermatitis caused by Eustoma exaltatum russellianum
      (lisianthus).

PMID- 24924814
TI  - Contact dermatitis caused by ascorbyl tetraisopalmitate in a cream used for the
      management of atopic dermatitis.

PMID- 24924815
TI  - Erythematous reactions on removal of Scanpor(r) tape in patch testing are not
      necessarily caused by dermographism.

PMID- 24924816
TI  - Response to and transport of brood by workers of Tapinoma erraticum (Formicidae;
      Dolichoderinae) during nest disturbance.
AB  - An attempt was made to describe the principle signals involved in the recognition
      of nymphs by Tapinoma workers. A behavioural measure, the way and extent to which
      workers transported different objects presented to them, was used to quantify
      this relationship. These objects were homo- or heterospecific nymphs, or
      different baits. Two types of test were generally used in such studies: retrieval
      - bringing back objects to the nest, and removal - transport of objects during
      displacement of the nest. The second type of test was used in this study. The
      results, in decreasing order of recognition were as follows. Tapinoma workers
      transport homospecific and Tetramorium nymphs at 100%. The smaller nymphs of
      Solenopsis impregnated with Tapinoma extract were transported at 77%. The nymphs
      of Solenopsis with their own odour were transported at 21%, paper impregnated.
      with Tapinoma extract at 12%, while 'odourless' Tapinoma nymphs and neutral paper
      were not transported at all. These results imply an intervention of both physical
      and chemical factors, the threshold significance of signals and their global
      implication depending on the test situation and its disturbing effect. They also
      depend on the nature of the different objects presented in combination; Tapinoma
      workers transport heterospecific brood much less readily in the presence of their
      own brood. The attractiveness of nymphs is not an all or none phenomenon. In a
      study of the adoption of homospecific nymphs from another nest, this gradation
      was apparent in the distribution of nymphs in the nest and their order of
      transport during removal tests; certain nymphs were left aside in the first 3
      days of presentation, were amongst the last to be transported during removal, and
      then by the most active workers. The perception of the brood by the workers may
      thus occur at different levels: (1) Perception of a factor that may be vaguely
      defined as 'transportable object' in a removal test - with objects of type
      'nymph' for example; (2) perception of the species; (3) perception of the colony.
      The worker ant during its life acquires a certain 'knowledge' of its own brood
      through familiarization, which expresses itself in terms of specific patterns of
      care for the brood, but this attention, although given preferentially to the
      brood, is not exclusive under stress. 

PMID- 24924817
TI  - Role of corticosterone in the control of post-shock fighting behaviour in male
      laboratory mice.
AB  - Two experiments were conducted to examine the role of corticosterone in
      controlling fighting subsequent to electric foot-shock in male mice. It was found
      that (1) treatment with corticosterone restores post-shock fighting in
      adrenalectomized males but not in castrated-adrenalectomized males; (2) raising
      cortieosterone levels induces post-shock fighting in castrated-adrenalectomized
      males treated with testosterone but not in castrated-adrenalectomized controls
      treated with a placebo; and (3) preventing corticosterone responses to shock
      occludes the increasing in fighting which normally follow shock in intact males.
      These findings suggest that (1) corticosterone plays an important role in the
      control of post-shock fighting in mice; (2) this importance of corticosterone is
      dependent on the presence of circulating testosterone, or other androgens; and
      (3) corticosterone responses to the experience of shock may be involved in the
      mediation of the facilitatory effects of this experience on subsequent fighting
      behaviour. 

PMID- 24924818
TI  - Different direct effects of light intensity on the entrained activity rhythm in
      neotropical bats (Chiroptera, Phyllostomidae).
AB  - In the two neotropical Chiroptera species, Artibeus lituratus and Phyllostomus
      discolor, the influence of illumination intensity during the D-time of an LD
      12:12 h on the locomotory activity rhythm was investigated by offering specific
      rectangular illumination schedules. In LD 12:12 (10(1):10(-4)lux), A. lituratus
      and P. discolor exhibit a stable unimodal basic activity pattern. By increasing
      the light intensity during D-time to 10(-1) lux the activity pattern, especially
      in A. lituratus, can be modified in almost every way. This indicates a strong
      direct inhibitory effect of higher light intensities (> 10(-4) lux). Hereby light
      effects via the circadian system have practically no importance. The response of
      A. lituratus to changes of the D-light intensity is more pronounced than that of
      P. discolor. It is suggested that the different direct effects of light intensity
      on the activity pattern of the two bat species reflect specific ecological
      adaptations. 

PMID- 24924819
TI  - Responsiveness to "social" releasers in cattle. II. Relation between social
      status and responsiveness, and possible effect of previous familiarization with
      the test conditions.
AB  - The data of two previous experiments, investigating the effects of social
      releasers in Friesian-Dutch heifers were analysed in order to verify whether the
      frequency of approach responses to models and calls of conspecifics was modified
      by pre-experimental factors. First, responsiveness was correlated to the social
      status of individuals; a social hierarchy was assessed on the basis of agonistic
      interactions recorded for a 2-month period prior to the experiments with models.
      A significant positive correlation was found between the total number of
      responses and the total number of escape-avoidance reactions to aggressive acts.
      The same result was found when individual ranks were assessed on a hierarchy re
      presenting a dominance order established on the basis of the number of aggressive
      acts causing escape-avoidance reactions. In this case, also, animals with highest
      ranks presented a significantly higher number of responses to models than animals
      with lowest ranks. In our second experiment, a significant positive correlation
      was found between all criteria used to assess individual ranks in a hierarchy,
      while this result was not found necessarily in the first experiment. The other
      pre-experimental factor under consideration was a possible familiarization with
      the testing conditions (models/calls of conspecifics, handling, and other
      procedures); some of the group-members tested during the second experiment had
      already been tested in the first one, carried out a year before. Many results
      demonstrated that the frequency of responses to social releasers was
      significantly lower for the previously tested subjects than for the animals
      tested for the first time. 

PMID- 24924820
TI  - Temperature dependence of visual fusion frequency in Rana lessonae cam., Bufo
      bufo L. and Bombina bombina (L.) (Amphibia).
AB  - The electroretinogram (ERG) was used to measure the flicker-fusion frequencies of
      Rana lessonae, Bufo bufo and Bombina bombina over the temperature range 5-25
      degrees C. In all three species the fusion frequency increased with increasing
      temperature. In the intermediate range of temperatures, the fusion frequencies of
      Rana lessonae and Bombina bombina doubled when the temperature was raised by 10
      degrees C. 

PMID- 24924821
TI  - Effects of social influence on neonatal approach responses of Gallus chicks.
AB  - Although most laboratory studies of imprinting rear and test subjects
      individually, in the natural setting birds are imprinted in groups. In order to
      approximate and evaluate naturally occuring conditions, the present study
      compared the approach responses of chicks reared and trained alone to those
      reared and trained in pairs to an audio-visual imprinting stimulus. The responses
      of both groups were virtually identical during the presence of the imprinting
      stimulus. However, under conditions of experimental extinction, the paired
      trained birds (now tested alone) were more resistant to extinction than their
      isolated counterparts, thus suggesting that birds with prior social experience
      are more strongly imprinted than has been previously reported. 

PMID- 24924822
TI  - Cortical arousal and social intimacy in the human female under different
      conditions of eye contact.
AB  - The EEG was monitored from pairs of female subjects while they engaged in varied
      eye contact under experimenter instruction (direct gaze, smile, averted gaze).
      The nine conditions of gaze were related monotonically to EEG abundance (9.5-20.0
      Hz). It is suggested that the gradient of arousal or activation so obtained is
      evidence of a physiological substrate of social intimacy. 

PMID- 24924827
TI  - Impact of urinary cadmium on mortality in the Japanese general population in
      cadmium non-polluted areas.
AB  - PURPOSE: The aim of the present study was to evaluate the dose-effect
      relationship between urinary cadmium (U-Cd as an index of internal Cd exposure)
      and mortality in a cohort of the Japanese general population. METHODS: A 19-year
      cohort study was conducted in 897 men and 1307 women who lived in two non
      polluted areas in Japan. The subjects were categorized into four quartiles based
      on creatinine adjusted U-Cd (MUg/g cre). Hazard ratio (HR) and 95% confidence
      interval (95%CI) of the quartiles of U-Cd for mortality was calculated using a
      proportional hazards regression. Forward stepwise model selection was applied to
      the potential covariates such as age, body mass index, mean arterial pressure,
      various lifestyle factors and present illness. RESULTS: The mortality rates per
      1000 person years were 27.8 and 12.5 in men and women, respectively. In men, the
      fourth quartile of U-Cd (>= 2.919 MUg/g cre) showed a significant, positive HR
      (1.50, 95%CI: 1.11-2.02) for mortality compared to the first quartile (< 1.014).
      In women, the fourth quartile of U-Cd (>= 3.943 MUg/g cre) also showed a
      significant HR (1.50, 95%CI: 1.08-2.09) for mortality compared to the first
      quartile (< 1.140). CONCLUSION: The present study clarified that U-Cd was
      significantly associated with increased mortality, indicating the worsened life
      prognosis of the general population in Cd non-polluted areas in Japan. These
      results highlight the importance of further discussion of the health risk
      assessment of Cd exposure in the general population.

PMID- 24924828
TI  - New outcomes for sexual health promotion.

PMID- 24924829
TI  - Characteristics of home care workers who leave their jobs: a cross-sectional
      study of job satisfaction and turnover in Washington State.
AB  - Attracting and retaining a stable and motivated home care workforce has become a
      top policy priority. We surveyed 402 former home care workers in Washington
      State. We compared these "leavers" to current home care workers recently
      surveyed. Those who left the profession were more highly educated, had higher
      household income, and were more likely to be White. Those newly employed have
      better benefits, wages, hours, and career mobility than in their home care jobs.
      The low status and poor pay of home care workers may result in the inability of
      the profession to retain those who face better prospects. 

PMID- 24924831
TI  - Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory,
      Australia 2007-2012.
AB  - INTRODUCTION: Australian Indigenous children suffer a high burden of diarrhoeal
      disease. Nitazoxanide is an antimicrobial that has been shown to be effective
      against a broad range of enteropathogens. To date, its use has not been reported
      in the tropical Top End (northernmost part) of the Northern Territory, Australia.
      The objective was to describe the use of nitazoxanide at the Royal Darwin
      Hospital, Northern Territory, and to assess any association with the time to
      resolution of diarrhoea. METHODS: Eligible children (<=13 years) were identified
      from dispensary records as having been prescribed nitazoxanide during the audit
      period, 1 July 2007 to 31 March 2012. Patient demographics, symptoms, diarrheal
      aetiology, treatment details and clinical outcomes were obtained by chart review.
      RESULTS: Twenty-eight children were treated with nitazoxanide, mostly for
      Cryptosporidium infection associated with prolonged diarrhoea. Dehydration was
      evident in 27 (96%) children on admission, and 11 (41%) were underweight.
      Diarrhoeal duration prior to treatment was 11.5 days (6.5 days pre- and 5 days
      post-admission). For children >=12 months, nitazoxanide was prescribed according
      to guidelines stipulated by the Centers for Disease Control and Prevention (CDC).
      Resolution of diarrhoea occurred a median of 2.4 days (IQR: 1.4-7.3) after
      starting treatment. An increase in weight for length at discharge was found for
      all children. CONCLUSIONS: Prompt resolution of diarrhoea without adverse
      outcomes suggests nitazoxanide may be an effective treatment for Cryptosporidium
      infection in this setting. Its role in the treatment of other causes of
      infectious diarrhoea needs further investigation. Randomised trials will further
      direct its use and determine optimal dosing regimens.

PMID- 24924830
TI  - Differentiating HIV-associated nephropathy from antiretroviral drug-induced
      nephropathy: a clinical challenge.
AB  - With the introduction of potent combination antiretroviral therapy (cART) into
      clinical practice, HIV-infected patients have garnered much benefit. However,
      kidney disease continues to be a potential complication in this group. Whereas
      HIV-associated nephropathy (HIVAN) was the major renal complication prior to
      cART, co-morbid diseases and adverse renal effects of various drugs, in
      particular cART, now complicate the landscape. Clinicians now must differentiate
      HIVAN from cART nephrotoxicity. While sometimes this is easy and relatively
      straightforward, often the clinician faces a difficult challenge distinguishing
      these two etiologies of kidney disease. This review will discuss HIVAN and cART
      related kidney disease and review the clinical and laboratory data that may be
      useful in differentiating these processes. Often, however, kidney biopsy may be
      required to differentiate HIVAN from cART nephrotoxicity as well as other kidney
      lesions associated with concurrent co-morbidities, both infectious and non
      infectious. 

PMID- 24924832
TI  - Effect of cropping systems on heavy metal distribution and mercury fractionation
      in the Wanshan mining district, China: implications for environmental management.
AB  - The authors studied the concentration of heavy metals and mercury fractionation
      in contaminated soil in 2 agricultural land use systems (paddy rice and dry land)
      at the Wanshan mercury mine in China. The average concentrations of chromium,
      lead, copper, nickel, and zinc were generally lower in paddy rice soil relative
      to corn field soil. Soil under corn field production was slightly contaminated
      with lead (22-100 mg/kg), copper (31-64 mg/kg), and nickel (22-76 mg/kg) and
      moderately contaminated with zinc (112-635 mg/kg). In both soils, correlation of
      these metals with the titanium concentration in the soil indicates a geogenic
      origin for each metal (lead, r = 0.48; copper, r = 0.63; nickel, r = 0.47; zinc,
      r = 0.48). The mercury and antimony concentration in soil was high under both
      cropping systems, and future remediation efforts should consider the potential
      environmental risk presented by these metals. The concentration of bioavailable
      mercury in soil ranged from 0.3 ng/g to 11 ng/g across the 2 cropping systems.
      The majority of mercury (>80%) was associated with organic matter and the
      residual fraction. However, soil under paddy rice production exhibited a
      significantly lower concentration of Fe/Mn oxide-bound mercury than that under
      corn field production. This may be a function of the reduction of Fe/Mn oxides in
      the paddy rice soil, with the subsequent release of adsorbed metals to the soil
      solution. Sequential change from corn field to paddy rice production, as
      practiced in Wanshan, should therefore be avoided. Mercury adsorbed to Fe/Mn
      oxides in corn field soil potentially could be released into the soil solution
      and be made available for biomethylation under the flooded water management
      conditions of a rice paddy.

PMID- 24924833
TI  - Deposition of superparamagnetic nanohydroxyapatite on iron-fibrin substrates:
      preparation, characterization, cytocompatibility and bioactivity studies.
AB  - In the present study, nanosized hydroxyapatite (nHAp) was formed on iron-fibrin
      substrates and its physico-chemical properties were characterized. The prepared
      iron-fibrin-nanohydroxyapatite (IF-nHAp) composite was needle shaped with an
      average width of about 30nm and length of 80nm. The vibrating sample magnetometer
      (VSM) was used to evaluate the superparamagnetic behavior of the nanocomposite,
      IF-nHAp. Hemolysis and ELISA (enzyme linked immunosorbent assay) were performed
      to evaluate the its bio/immunocompatibility and MTT (3-(4,5-dimethylazol-2-yl)
      2,5-diphenyl-tetrazolium bromide) assay using osteoblast cells was performed to
      scrutinize its proliferative potential. Alkaline phosphatase activity (ALP) and
      calcium deposition were studied to investigate the osteogenic property of the
      nanocomposite. RT-PCR (real time-polymerase chain reaction) was used to quantify
      the mRNA levels of ALP, OC (osteocalcin), and OPN (osteopontin) genes involved in
      the osteogenic differentiation and matrix mineralization. Further, the bone
      bonding ability of IF-nHAp was observed by the deposition of apatite layers on
      the composite incubated in simulated body fluid (SBF). 

PMID- 24924834
TI  - Fusion protein bilayer fabrication composed of recombinant azurin/cytochrome P450
      by the sortase-mediated ligation method.
AB  - Recently, the fabrication of protein bilayer has been required for the
      development of protein or enzyme complex formation. In the present study, we
      fabricated a fusion protein bilayer composed of recombinant azurin-cytochrome
      P450, which was synthesized by a site-specific sortase-mediated ligation method.
      The Pseudomonas aeruginosa azurin was modified by DNA recombinant technique, for
      enzymatic ligation and immobilization. The Pseudomonas putida cytochrome P450 was
      also modified for enzymatic ligation. The recombinant metalloproteins were
      conjugated via the sortase A. The conjugation was confirmed by SDS-PAGE and UV
      vis. Then, the prepared fusion protein was immobilized on Au substrate, by the
      self-assembly method. The Azu-P450 (recombinant azurin-cytochrome P450) fusion
      protein layer was confirmed by AFM (Atomic Force Microscopy) and SERS (Surface
      enhanced Raman Spectroscopy), to confirm the fusion protein bilayer orientation.
      Moreover, the electrochemical property of Azu-P450 was observed by cyclic
      voltammetry (CV). As a result, the Azu-P450 fusion protein bilayer shows good
      orientation on the Au substrate. Also, the original redox property of this fusion
      protein bilayer has been well maintained. The proposed fusion protein bilayer
      can. 

PMID- 24924835
TI  - Diffusion kurtosis imaging study of prostate cancer: preliminary findings.
AB  - PURPOSE: To evaluate the differences in parameters of diffusion kurtosis imaging
      (DKI) between prostate cancer, benign prostatic hyperplasia (BPH), and benign
      peripheral zone (PZ). MATERIALS AND METHODS: Twenty-four foci of prostate cancer,
      41 BPH nodules (14 stromal and 27 nonstromal hyperplasia), and 20 benign PZ from
      20 patients who underwent radical prostatectomy were investigated. Diffusion
      weighted imaging (DWI) was performed using 11 b-values (0-1500 s/mm(2) ). DKI
      model relates DWI signal decay to parameters that reflect non-Gaussian diffusion
      coefficient (D) and deviations from normal distribution (K). A mixed model
      analysis of variance and receiver operating characteristic (ROC) analyses were
      performed to assess the statistical significance of the metrics of DKI and
      apparent diffusion coefficient (ADC). RESULTS: K was significantly higher in
      prostate cancer and stromal BPH than in benign PZ (1.19 +/- 0.24 and 0.99 +/-
      0.28 versus 0.63 +/- 0.23, P < 0.001 and P < 0.001, respectively). K showed a
      trend toward higher levels in prostate cancer than in stromal BPH (1.19 +/- 0.24
      versus 0.99 +/- 0.28, P = 0.051). On the ROC analyses, a significant difference
      in area under the curve was not observed between K and ADC, however, K showed the
      highest sensitivity among three parameters. CONCLUSION: DKI may contribute to the
      imaging diagnosis of prostate cancer, especially in the differential diagnosis of
      prostate cancer and BPH.

PMID- 24924836
TI  - Fluorescence in situ hybridization analysis of atypical melanocytic
      proliferations and melanoma in young patients.
AB  - Morphologic heterogeneity among melanocytic proliferations is a common challenge
      in the diagnosis of melanoma. In particular, atypical melanocytic lesions in
      children, adolescents, and young adults may be difficult to classify because of
      significant morphologic overlap with melanoma. Recently a four-probe fluorescence
      in situ hybridization (FISH) protocol to detect chromosomal abnormalities in
      chromosomes 6 and 11 has shown promise for improving the classification of
      melanocytic lesions. We sought to determine the correlation between FISH results,
      morphology, and clinical outcomes in a series of challenging melanocytic
      proliferations in young patients. We retrospectively performed the standard four
      probe FISH analysis on 21 melanocytic neoplasms from 21 patients younger than 25
      years of age (range 5-25 years, mean 14.6 years) from Stanford University Medical
      Center who were prospectively followed for a median of 51 months (range 1-136
      months). The study cohort included patients with 5 confirmed melanomas, 2
      melanocytic tumors of uncertain malignant potential (MelTUMPs), 10
      morphologically challenging atypical Spitz tumors (ASTs), and 4 typical Spitz
      nevi. FISH detected chromosomal aberrations in all five melanomas and in one
      MelTUMP, in which the patient developed subsequent lymph node and distant
      metastasis. All 10 ASTs, 4 Spitz nevi, and 1 of 2 MelTUMPs were negative for
      significant gains or losses in chromosomes 6 and 11q. Our findings demonstrated a
      strong correlation between positive FISH results and the histomorphologic
      impression of melanoma. This finding was also true for the MelTUMP with poor
      clinical outcome. Therefore FISH may serve as a helpful adjunct in the
      classification of controversial melanocytic tumors in young patients.

PMID- 24924837
TI  - Involvement of p38 mitogen-activated protein kinase in acquired gemcitabine
      resistant human urothelial carcinoma sublines.
AB  - Resistance to chemotherapeutic drugs is one of the major challenges in the
      treatment of cancer. A better understanding of how resistance arises and what
      molecular alterations correlate with resistance is the key to developing novel
      effective therapeutic strategies. To investigate the underlying mechanisms of
      gemcitabine (Gem) resistance and provide possible therapeutic options, three Gem
      resistant urothelial carcinoma sublines were established (NG0.6, NG0.8, and
      NG1.0). These cells were cross-resistant to arabinofuranosyl cytidine and
      cisplatin, but sensitive to 5-fluorouracil. The resistant cells expressed lower
      values of [hENT1 * dCK/RRM1 * RRM2] mRNA ratio. Two adenosine triphosphate
      binding cassette proteins ABCD1 as well as multidrug resistance protein 1 were
      elevated. Moreover, cyclin D1, cyclin-dependent kinases 2 and 4 were upregulated,
      whereas extracellular signal-regulated kinase 1/2 and p38 mitogen-activated
      protein kinase (MAPK) activity were repressed significantly. Administration of
      p38 MAPK inhibitor significantly reduced the Gem sensitivity in NTUB1 cells,
      whereas that of an extracellular signal-regulated kinase MAPK inhibitor did not.
      Furthermore, the Gem-resistant sublines also exhibited higher migration ability.
      Forced expression of p38 MAPK impaired the cell migration activity and augmented
      Gem sensitivity in NG1.0 cells. Taken together, these results demonstrate that
      complex mechanisms were merged in acquiring Gem resistance and provide
      information that can be important for developing therapeutic targets for treating
      Gem-resistant tumors.

PMID- 24924838
TI  - Protective effects of cerebrolysin in a rat model of optic nerve crush.
AB  - To investigate the effects of cerebrolysin (Cbl) on optic nerves (ON) and retinal
      ganglion cells (RGC) in a rat model of ON crush. Rats received intravitreal
      injection of Cbl (n = 20), intra-ON injection of Cbl (n = 20), intraperitoneal
      injection (IPI) of Cbl (n = 20), or phosphate buffered saline (PBS; n = 20) every
      day for 2 weeks after ON crush injury. At 3 weeks post-trauma, RGC density was
      counted by retrograde labeling with FluoroGold and visual function was assessed
      by flash visual-evoked potentials. Activities of microglia after insults were
      quantified by immunohistochemical analysis of the presence of ED1 in the optic
      nerve. At 3 weeks postcrush, the densities of RGCs in the Cbl-IVI group (1125 +/-
      166/mm(2)) and in the Cbl-IPI treatment group (1328 +/- 119/mm(2)) were
      significantly higher than those in the PBS group (641 +/- 214/mm(2)). The flash
      visual-evoked potential measurements showed that latency of the P1 wave was
      significantly shorter in the Cbl-IVI- and Cbl-IPI-treated groups (105 +/- 4 ms
      and 118 +/- 26 ms, respectively) than in the PBS-treated group (170 +/- 20 ms).
      However, only Cbl IPI treatment resulted in a significant decrease in the number
      of ED1-positive cells at the lesion sites of the ON (5 +/- 2 cells/vs. 30 +/- 4
      cells/high-power field in control eyes). Treatment with intra-ON injection of Cbl
      was harmful to the optic nerve in the crush model. Systemic administration of Cbl
      had neuroprotective effects on RGC survival and visual function in the optic
      nerve crush model.

PMID- 24924839
TI  - Interleukin-23 and its correlation with disease activity, joint damage, and
      functional disability in rheumatoid arthritis.
AB  - The purpose of this study was to compare the serum interleukin (IL)-23 levels
      between rheumatoid arthritis (RA) patients and healthy controls and to determine
      the correlation of IL-23 levels with disease activity, joint damage and
      functional disability in RA. Serum samples were obtained from 45 patients with RA
      and 45 healthy controls. The enzyme-linked immunosorbent assay method was used
      for quantitative analysis of IL-23. All the RA patients were assessed for disease
      activity based on the 28-joint disease activity score, joint damage based on
      modified Sharp score, and functional ability using the Health Assessment
      Questionnaire-Disability Index. The mean serum IL-23 level was much higher among
      the RA patients (24.50 +/- 13.98 pg/mL) compared to the controls (5.98 +/- 3.40
      pg/mL; p < 0.01). There was a significant positive relationship between IL-23
      levels and disease activity and questionnaire scores (p = 0.003 and 0.020,
      respectively). On logistic regression analysis, IL-23 levels were significantly
      higher in patients with moderate to high disease activity (p = 0.008, odds ratio
      = 1.073, 95% confidence interval = 1.019-1.130) and patients with significant
      functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval =
      1.021-1.153). RA patients have significantly higher levels of serum IL-23. The IL
      23 levels correlate well with disease activity and functional disability but not
      with radiographic joint damage.

PMID- 24924840
TI  - Effects of metabolic syndrome, apolipoprotein E, and CYP46 on cognition among
      Taiwanese Chinese.
AB  - The combined effects of metabolic syndrome and the apolipoprotein E and CYP46
      genotypes on the risk of cognitive decline has yet to be determined among
      Taiwanese Chinese. Two hundred and nine mentally healthy middle-aged and older
      adults were assessed for metabolic syndrome, cognitive function using the
      Cognitive Abilities Screening Instrument, Mini-Mental State Examination, ApoE,
      and CYP46 polymorphisms. There were no differences in cognitive performance, ApoE
      epsilon4 (epsilon4) carrier status, or CYP46 genotypes between participants with
      and those without metabolic syndrome. The epsilon4 carriers and participants with
      the AA allele of CYP46 had significantly lower mental manipulation score.
      Metabolic syndrome and epsilon4 had synergistic effects on cognitive decline.
      Therefore, the epsilon4 carriers and participants with the AA allele of CYP46
      have decreased mental manipulation ability. The metabolic syndrome may play a
      role in subtle cognitive dysfunction in epsilon4 carriers among Taiwanese
      Chinese.

PMID- 24924841
TI  - Combined estrogen replacement therapy on metabolic control in postmenopausal
      women with diabetes mellitus.
AB  - Previous studies have shown that the incidence of diabetes is higher when women
      come to menopause. This study was carried out to examine the effects of combined
      estrogen replacement therapy (ERT) on diabetes in postmenopausal women.
      PubMed/MEDLINE was searched for English-language articles published between
      January 1997 and June 2011. Studies that examined ERT on the incidence of
      diabetes and randomized clinical trials that evaluated combined ERT (estrogen
      plus progesterone) on diabetic indices in postmenopausal women were included.
      Pooled relative risks were calculated using a random- or a fixed-effects model.
      Sixteen studies comprising 17,971 cases were included. Based on the pooled data,
      ERT significantly reduced the incidence of diabetes [odds ratio (OR), 0.61; 95%
      confidence interval (CI), 0.55-0.68, ERT past/current/continuous use vs. never
      use; OR, 0.57; 95% CI, 0.51-0.65, ERT current/continuous use vs. past/never use].
      Women with combined ERT have significantly lower levels of fasting plasma glucose
      (mean difference, -1.41 mM/L; 95% CI, -2.49 to -0.33 mM/L) and HbA1c (mean
      difference, -0.73%; 95% CI, from -1.28 to -0.18%) compared with placebo.
      Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean
      difference, -0.34 mM/L; 95% CI, from -0.53 to -0.15 mM/L) and low-density
      lipoprotein (mean difference, -0.43 mM/L; 95% CI, from -0.71 to -0.14 mM/L) but
      slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI,
      from -0.07 to 0.12 mM/L) levels as compared with placebo control. This systemic
      review and meta-analysis provides evidence that postmenopausal women taking low
      dose combined ERT have a decreased risk of developing diabetes and have better
      diabetic control.

PMID- 24924842
TI  - The efficacy of shock wave therapy in patients with knee osteoarthritis and
      popliteal cyamella.
AB  - This randomized, controlled study was performed to compare the effects of
      extracorporeal shockwave therapy (ESWT) and ultrasound on the rehabilitation of
      knee osteoarthritis with popliteal cyamella. One hundred and twenty patients with
      bilateral moderate knee osteoarthritis (Altman III) and popliteal cyamella were
      selected and randomly assigned to four groups (GI-GIV). Patients in Groups I-III
      received isokinetic muscular strengthening exercises three times weekly for 8
      weeks. Group II received pulse ultrasound treatment for popliteal cyamella three
      times weekly for 8 weeks, Group III received weekly shock wave therapy for
      popliteal cyamella for the first 6 weeks, and Group IV acted as controls. The
      therapeutic effects were evaluated by changes in the arthritic knees range of
      motion (ROM), visual analogue scale, Lequesne's index, and muscle peak torques
      after treatment and at follow-up 6 months later. Each treated group exhibited
      increased muscle peak torques and significantly reduced pain and disability after
      treatment and at follow-ups. However, only patients in Groups II and III showed
      significant improvements in ROM after treatment, and only participants in Group
      III showed immediate improvement in ROM after each treatment. Patients in Group
      III also showed the greatest increase in muscular strength and the greatest
      decrease in disability after treatment and at the follow-ups. ESWT is better than
      pulse ultrasound in rehabilitation of patients with knee osteoarthritis and
      popliteal cyamella results in more functional improvements.

PMID- 24924843
TI  - Synchronous bladder and prostate cancers in the specimens of radical
      cystoprostatectomy: a multicenter retrospective analysis.
AB  - The purpose of this study was to evaluate the features of prostate cancer that
      have been incidentally detected in radical cystoprostatectomy specimens of
      bladder cancer patients. The researchers of the current study retrospectively
      evaluated the data from 119 men who underwent radical cystoprostatectomy at four
      referral institutions in Ankara, Turkey. Of the 21 prostate cancer patients, 17
      (81%) were aged >= 60 years; 10 (47.6%) had clinically significant diseases;
      three had a Gleason score of 6, three had a Gleason score of 7, three had a
      Gleason score of 8, one had a positive surgical margin along with extracapsular
      invasion of the tumor and a high Gleason score, and three patients had a tumor
      volume of >= 0.5 cm(3), of which two also had a high Gleason score. Patients were
      followed-up for a mean of 29 +/- 10.2 months; the overall survival was 96.6% (n =
      115) during that period. Preoperative digital rectal examination and prostate
      specific antigen values did not differ between the benign and prostate cancer
      groups. There was no survival advantage in the insignificant prostate cancer and
      benign prostate groups. No additional benefit for predicting prostate cancer was
      found with digital rectal examination and prostate-specific antigen tests,
      although some clinicians advised such. In patients aged < 60 years, organ-sparing
      cystectomy seems reasonable. In prostate-sparing surgery, candidates who are aged
      >60 years, the preoperative work-up may routinely include prostate biopsy,
      especially the apex. Preoperative findings of multifocality of bladder cancers
      and the presence of carcinoma in situ have the risk of prostatic involvement.

PMID- 24924844
TI  - Left ventricular noncompaction cardiomyopathy: an under-recognized disease
      diagnosed by echocardiography and computed tomography.

PMID- 24924845
TI  - Recurrent intussusception caused by intestinal metastasis of pulmonary
      pleomorphic carcinoma.

PMID- 24924846
TI  - Primary axillary anaplastic large cell lymphoma mimicking pyogenic granuloma
      clinically.

PMID- 24924847
TI  - Concept formation and categorization of complex, asymmetric, and impossible
      figures.
AB  - Impossible figures are striking examples of inconsistencies between global and
      local perceptual structures, in which the overall spatial configuration of the
      depicted image does not yield a coherent three-dimensional object. In order to
      investigate whether structural "impossibility" is an important perceptual
      property of depicted objects, we used a category formation task in which subjects
      were asked to divide pictures of shapes into groups that seemed most natural to
      them. Category formation is usually unidimensional, such that sorting is
      dominated by a single perceptual property, so this task can serve as a measure of
      which dimensions are most salient. In Experiment 1, subjects received sets of 12
      line drawings consisting of six possible and six impossible objects. Very few
      subjects grouped the figures by impossibility on the first try, and only half did
      so after multiple attempts at sorting. In Experiment 2, we investigated other
      global properties of figures: symmetry and complexity. Subjects readily sorted
      objects by complexity, but seldom by symmetry. In Experiment 3, subjects were
      asked to draw each of the figures before sorting them, which had only a minimal
      effect on categorization. Finally, in Experiment 4, subjects were explicitly
      instructed to divide the shapes by symmetry or impossibility. Performance on this
      task was perfect for symmetry, but not for impossibility. Although global
      properties of figures seem extremely important to our perception, the results
      suggest that some of these cues are not immediately obvious or salient for most
      observers. 

PMID- 24924848
TI  - Size (mostly) doesn't matter: the role of set size in object substitution
      masking.
AB  - Conscious detection and discrimination of a visual target stimulus can be
      prevented by the presentation a spatially nonoverlapping, but temporally
      trailing, visual masking stimulus. This phenomenon, known as object substitution
      masking (OSM), has long been associated with spatial attention, with diffuse
      attention seemingly being key for the effect to be observed. Recently, this
      hypothesis has been questioned. We sought to provide a definitive test of the
      involvement of spatial attention in OSM by using an eight-alternative forced
      choice task under a range of mask durations, set sizes, and target/distractor
      spatial configurations. The results provide very little evidence that set size,
      and thus the distribution of spatial attention, interacts with masking magnitude.
      These findings have implications for understanding the mechanisms underlying OSM
      and the relationship between consciousness and attention. 

PMID- 24924849
TI  - The error protection impact of inhibitory after-effects in a location-based task
      and its preservation with practice.
AB  - In location-based tasks, responses related to (prime trial) distractor-occupied
      locations automatically undergo activation, followed by inhibition, which causes
      these responses to become execution-resistant (ER). Distractor-response ER takes
      time to override, delaying target reactions that later require this response
      (e.g., probe, ignored-repetition trials), causing the spatial negative priming
      (SNP) phenomenon. We learned in this study that distractor-response ER affords
      this output a degree of error protection. Specifically, when the probe target
      appeared at a new location, former (prime) distractor responses were used
      erroneously significantly less often than their control response counterparts,
      likely due to their ER feature, which discourages their inappropriate selection
      (i.e., "ER" provides error protection). This error protection also was evident
      when a previous distractor response was activated by a distractor on the probe
      (i.e., distractor-repeat trial). Notably, error protection remained effective
      over extensive practice, as did SNP size (i.e., ER override time) after an
      initial decline. 

PMID- 24924850
TI  - Olfactory-visual congruence effects stable across ages: yellow is warmer when it
      is pleasantly lemony.
AB  - This study aimed to examine the age-related differences in the olfactory-visual
      cross-correspondences and the extent to which they are moderated by the odors
      pleasantness. Sixty participants aged from 20- to 75- years (young, middle-aged
      and older adults) performed a priming task to explore the influence of six
      olfactory primes (lemon, orange, rose, thyme, mint and fish) on the
      categorization (cool vs. warm) of six subsequent color targets (yellow, orange,
      pink, malachite green, grass-green, and blue-gray). We tested mixed effects
      models. Response times were regressed on covariates models using both fixed
      effects (Groups of age, olfactory Pleasantness and multimodal Condition) and
      cross-random effects (Subject, Color and Odor). The random effects coding for
      Odor (p < .001) and Color (p = .001) were significant. There was a significant
      interaction effect ( p= .004) between Condition * Pleasantness, but not with
      Groups of age. The compatibility effect (i.e., when odors and colors were
      congruent, the targets processing were facilitated) was as much enhanced as the
      olfactory primes were pleasant. Cross-correspondences between olfaction and
      vision may be robust in aging. They should be considered alongside spatiotemporal
      but also emotional congruency. 

PMID- 24924851
TI  - Can intermittent theta burst stimulation as add-on to psychotherapy improve
      nicotine abstinence? Results from a pilot study.
AB  - Smoking is among the leading causes of mortality worldwide. Discontinuing smoking
      can increase life expectancy to the presmoking level. Unaided attempts are often
      ineffective, strengthening the necessity of cognitive-behavioral therapy (CBT),
      nicotine replacement or pharmacotherapy. Still, relapse rates are high. Recently,
      a modulation of nicotine craving, which predicts relapse, through transcranial
      magnetic stimulation to the prefrontal cortex was shown. In a pilot study, we
      investigated whether 4 sessions of intermittent theta burst stimulation (iTBS) as
      add-on treatment to CBT reduces nicotine craving and improves long-term
      abstinence (at 3, 6 and 12 months). Smokers were randomly assigned to a treatment
      (n = 38) or a sham group (n = 36). Although we did not find reduced craving, we
      could show higher abstinence rates in the treatment group at 3 months. At 6 and
      12 months abstinence rates did not differ significantly. Results at 12 months,
      however, have to be interpreted cautiously due to significant differences in the
      dropout rates between the two groups at this time point. We provide first
      evidence for a beneficial effect of additional iTBS on intermediate nicotine
      abstinence; however, the low number of iTBS sessions might have prevented longer
      effects. More lasting effects might be achieved by iTBS maintenance sessions in
      analogy to the treatment of depression.

PMID- 24924852
TI  - From transposon to chromosome and polyploidy. An update on cytogenetics and
      genomics of Arabidopsis.

PMID- 24924854
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health. The Core Outcomes in Women's Health (CROWN) Initiative.

PMID- 24924853
TI  - Chromosome synapsis and recombination in simple and complex chromosomal
      heterozygotes of tuco-tuco (Ctenomys talarum: Rodentia: Ctenomyidae).
AB  - The chromosomal speciation hypothesis suggests that irregularities in synapsis,
      recombination, and segregation in heterozygotes for chromosome rearrangements may
      restrict gene flow between karyotypically distinct populations and promote
      speciation. Ctenomys talarum is a South American subterranean rodent inhabiting
      the coastal regions of Argentina, whose populations polymorphic for Robertsonian
      and tandem translocations seem to have a very restricted gene flow. To test if
      chromosomal differences are involved in isolation among its populations, we
      examined chromosome pairing, recombination, and meiotic silencing of unsynapsed
      chromatin in male meiosis of simple and complex translocation heterozygotes using
      immunolocalization of the MLH1 marking mature recombination nodules and
      phosphorylated histone gammaH2A.X marking unrepaired double-strand breaks. We
      observed small asynaptic areas labeled by gammaH2A.X in pericentromeric regions
      of the chromosomes involved in the trivalents and quadrivalents. We also observed
      a decrease of recombination frequency and a distalization of the crossover
      distribution in the heterozygotes and metacentric homozygotes compared to
      acrocentric homozygotes. We suggest that the asynapsis of the pericentromeric
      regions are unlikely to induce germ cell death and decrease fertility of the
      heterozygotes; however, suppressed recombination in pericentromeric areas of the
      multivalents may reduce gene flow between chromosomally different populations of
      the Talas tuco-tuco. 

PMID- 24924855
TI  - Microbial, chemical and sensory properties of shalgams made using different
      production methods.
AB  - BACKGROUND: Shalgam is a traditional Turkish lactic acid fermented beverage. This
      study examined the microbial, chemical and sensory characteristics of shalgams
      produced by various methods. RESULTS: Different production methods using
      traditional method (dough fermentation and carrot fermentation), direct method
      (without dough fermentation) and with the addition of starter cultures were
      applied to produce shalgams. The final amounts of total acidity as lactic acid
      (6.33-9.22 g L(-1)), pH (3.42-3.55), the counts of lactic acid bacteria (7.43
      7.74 log CFU mL(-1)), total mesophilic aerobic bacteria (7.03-7.46 log CFU mL(
      1)), yeasts (6.96-7.50 log CFU mL(-1)) and non-Saccharomyces yeasts (4.21-5.19
      log CFU mL(-1) ) were found. Lactobacillus plantarum and then Lb. buchneri were
      the most frequently isolated bacteria in shalgam samples. Sensory evaluation of
      shalgams showed that sample produced using traditional method with starter
      additions obtained highest scores. CONCLUSION: This study showed that addition of
      starter lactic acid bacteria cultures improved the quality of shalgams. Analysis
      of the results indicated that the direct method for the production of shalgam is
      not preferable. The data obtained can be useful for industrial shalgam producers.

PMID- 24924856
TI  - Expect the (un)expected: a hazardous cause of tako-tsubo cardiomyopathy.

PMID- 24924857
TI  - Risk factors associated with leg disorders of gestating sows in different group
      housing systems: a cross-sectional study in 108 farrow-to-finish farms in France.
AB  - Group-housing, rather than individual-housing systems, is mandatory for gestating
      sows in the European Union (2008/120/EEC). However, leg problems occur more
      frequently in group-housing than in individual-housing systems and are a welfare
      and health concern. A cross-sectional study involving 108 farms in western France
      was carried out to see whether the type of the 4 main group-housing systems (i.e.
      large groups with electronic feeder station in stable or in dynamic groups, small
      groups in walk-in lock-in stalls or partial feeding stalls), and other husbandry
      practices, were associated with leg disorders. In each farm, the sows were
      examined visually for claw lesions, scored for lameness and their breeding
      characteristics were recorded. Lameness was positively correlated with heel
      lesions and dewclaw lesions. A concrete slatted floor, as compared to straw, was
      a major risk factor (unadjusted relative risk (RR)=9.9; 95% confidence interval
      (95% CI): 4.4-34.5). Walk-in lock-in stalls were found to be the most protective
      system. A logistic regression model was used to identify those factors which
      significantly increased the risk of leg problems. These factors were: housing in
      large groups (RR=1.5; 95% CI: 1.1-2.4), dirty floors (RR=1.6; 95% CI: 1.0-2.9),
      high level of ammonia (RR=1.5; 95% CI: 1.1-2.1), severely restricted feeding
      particularly during the last stage of pregnancy (RR=1.5; 95% CI: 1.0-2.1) and a
      high number of sows per stockman (RR=1.5; 95% CI: 1.0-2.4). 

PMID- 24924858
TI  - Quantitative assessment of the risk of introduction of bovine viral diarrhea
      virus in Danish dairy herds.
AB  - A quantitative risk assessment was carried out to estimate the likelihood of
      introducing bovine viral diarrhea virus (BVDV) in Danish dairy herds per year and
      per trimester, respectively. The present study gives important information on the
      impact of risk mitigation measures and sources of uncertainty due to lack of
      data. As suggested in the Agreement on the Application of Sanitary and
      Phytosanitary Measures (SPS Agreement), the OIE Terrestrial Animal Health Code
      was followed for a transparent science-based risk assessment. Data from 2010 on
      imports of live cattle, semen, and embryos, exports of live cattle, as well as
      use of vaccines were analyzed. Information regarding the application of
      biosecurity measures, by veterinarians and hoof trimmers practicing in Denmark
      and in other countries, was obtained by contacting several stakeholders, public
      institutions and experts. Stochastic scenario trees were made to evaluate the
      importance of the various BVDV introduction routes. With the current surveillance
      system, the risk of BVDV introduction was estimated to one or more introductions
      within a median of nine years (3-59). However, if all imported animals were
      tested and hoof trimmers always disinfected the tools used abroad, the risk could
      be reduced to one or more introductions within 33 years (8-200). Results of this
      study can be used to improve measures of BVD surveillance and prophylaxis in
      Danish dairy herds. 

PMID- 24924859
TI  - Discrimination of song types by male great tits.
AB  - The purposes of this study were: to test whether male song birds could be trained
      to discriminate between a reference song type and a set of other types and to see
      if in learning the discrimination the birds had formed a category of "reference
      song" as opposed to "others". Three male great tits learned to discriminate
      between a reference song type (B) and 10 others. All of them showed an
      improvement with experience, although the final scores and consistency varied
      between individuals. In spite of the variability among birds some of the 10 song
      types were easier to discriminate from B than others. Two of the birds achieved
      at least 80% of discrimination, but only one of them yielded good data in the
      following categorization tests: In one session the bird was presented with 20
      novel "other" song types and the same reference type B. This bird treated all 20
      types as "others". Therefore, the bird appears to have formed the category
      "other". In two other sessions the bird was presented with 40 different versions
      of B (as classified by the authors) recorded from 40 different individual birds,
      and the same 10 training "others". The bird categorized 16 out of the 40 Bs as B,
      and overall discriminated significantly between Bs and the 10 other types.
      Therefore, this bird generalized the stimulus song B to other related stimuli. We
      conclude that, although our results are preliminary, they at least indicate a
      method of studying how birds categorize songs. 

PMID- 24924860
TI  - Changes in social behavior and brain catecholamines during the development of
      ascorbate deficiency in Guinea pigs.
AB  - Behavioral patterns of pairs of guinea pigs were recorded in 15-min observation
      sessions on alternate days during a 6-day baseline phase and a 21- to 25-day
      period following the introduction of an ascorbate-free diet. Ascorbate-deficient
      animals were compared to two pair-fed control groups. During the last 5 days of
      the experiment, marked reductions in frequency and/or cumulative duration of
      active behaviors (e.g. locomotion, rearing, social grooming) were observed in the
      ascorbate- deficient group, while duration of inactivity in proximity to the test
      partner increased greatly. The decline in probability of locomotion was greater
      at long temporal lags (> 15 sec) after locomotion of the test partner than at
      short lags. Evidence of behavioral changes began to appear after 9-13 days on the
      ascorbate-free diet. Assays of brain tissue after sacrifice on the last day of
      the experiment revealed significant reductions in concentrations of ascorbate and
      norepinephrine. Some behavioral measures were highly correlated with brain
      ascorbate but not with brain norepinephrine, suggesting that other transmitter
      systems are involved in mediating the behavioral changes. The results also
      suggest the value of measurement of social behavior in assessing the behavioral
      effects of dietary or other treatments. 

PMID- 24924861
TI  - Running and drinking by rats outside the schedule session.
AB  - Two experiments measured the effects of a contingency schedule relating running
      and eating on the behavior of rats during an "experimental hour" and during two
      hours before and afterwards. The behaviors recorded during the surrounding hours
      were drinking and perching (Experiment 1) and running, drinking and perching
      (Experiment 2). The temporal pattern of drinking in both experiments was
      unaffected by changes in conditions during the experimental hour. However,
      drinking prior to the experimental hour in Experiment 2 was less than in
      Experiment 1 probably due to competition from wheel running. Rats showed
      unreliable patterns of perching in both experiments. Finally, running increased
      both within and outside the experimental hour during the schedule conditions. The
      increase in wheel running surrounding the schedule hour may represent a
      combination of species-typical foraging responses and the failure of stimulus
      control of instrumental behavior. These data suggest that behavior regulation and
      optimality theories may need to consider the species-typical mechanisms and
      stimulus control necessary for animals to integrate behavior over time. 

PMID- 24924862
TI  - Positive local contrast and s- duration: Theories of local contrast and a
      resolution.
AB  - Pigeons were exposed to a simple sequence in which an S+, presented for a fixed
      duration, was alternated with three durations of an S-. Both positive and
      negative local contrast appeared as distinctive patterns of responding and S+
      responding depended upon the duration of the preceding S-. Response rates in S+
      were higher after the two longer S- durations than after the briefest S-. The
      effect of S- duration was partially independent of the presence or absence of a
      clear pattern of positive local contrast in S+. Additionally, all birds showed
      Skinnerian induction in S+ (depressed responding during the first half of the
      presentation) when the preceding S- was the briefest of the three durations.
      Additivity theory and response competition theory are both unable to account for
      these and other local contrast phenomena. However, a liberal interpretation of
      additivity theory, better termed a "Pavlovian-process" theory, can do so in a
      very straightforward way. 

PMID- 24924863
TI  - Scaling of events spaced in time.
AB  - Pigeons were trained to peck on a key, which could be lit by red or green light,
      and produce feeder-light stimuli intermittently. On some trials, food followed
      the fourth feeder flash providing the key color was red, while on other trials
      food followed the sixteenth flash providing the color was green. The change in
      color from red to green was produced by a peck to a second, changeover key.
      Pigeons typically responded in the presence of red until four or more flashes
      occured and then, if food had not been delivered, changed the main-key color and
      responded on the green key. Following training, the variable-interval schedule
      arranging-feeder light events was changed to longer and shorter values to alter
      the amount of time (and number of responses) between events. Data from these test
      days indicate that the change from red to green was influenced by the number of
      events, but also by the time elapsed and/or responses emitted since the onset of
      a trial. The results suggest multiple sources of related information and stimulus
      control when events and behavior occur over time. 

PMID- 24924864
TI  - Responding on random interval schedules with high rates of reinforcement.
AB  - Four rats leverpressing for food were exposed to a series of random interval
      schedules that provided high rates of reinforcement. In three of the four rats,
      response rates decreased with increases in obtained reinforcement rates. In two
      subjects, response rates maintained by the two schedules with the highest
      reinforcement rates differed even though the obtained reinforcement rates were
      approximately equivalent. The results generally support theories which predict a
      bitonic relation between response rate and reinforcement rate. They also suggest
      that, in the development and testing of models, more attention needs to be paid
      to schedule feedback functions and the role of the scheduled reinforcement rate. 

PMID- 24924865
TI  - Olfactorily mediated attack suppression in the southern grasshopper mouse toward
      an unpalatable prey.
AB  - Predatory behavior toward an unpalatable sympatric prey was examined in the
      southern grasshopper mouse, Onychomy torridus (Coues). Mice preferred the
      palatable grasshopper Brachystola magna over the unpalatable secretion-producing
      grasshopper Taeniopoda eques. Consumption of T. eques decreased 35% while
      consumption of B. magna remained stable during three nights of testing.
      Olfactorily mediated attack suppression was demonstrated when O. torridus
      rejected palatable B. magna which had been coated with 5 ul of T. eques defense
      secretion. These results show that O. torridus discriminates and is capable of
      rejecting prey at any point in the prey capture sequence. These are adaptive
      attributes for a predator like O. torridus, which commonly attacks well-defended
      or dangerous prey. 

PMID- 24924866
TI  - Breeding experience and parental behaviour in convict cichlids (Cichlasoma
      nigrofasciatum ).
AB  - Changes in the levels of activities by parental female and male convict cichlids
      were studied over three successive reproductive episodes and within each episode.
      No evidence was found for behavioural maturation independent of experience. With
      successive episodes, young survived for longer times, nests were cleaner, males
      ate less and females more, and males became more aggressive while females focused
      more on the nest. Within an episode there were also marked variations in
      activities by each sex. Reproductive behaviour is therefore open in a number of
      respects both within and across episodes to environmental inputs. 

PMID- 24924867
TI  - Nest-box exploration and choice in male and female mice tested under individual
      and social conditions.
AB  - Nest-box exploration and the choice of nest site were studied in the laboratory
      mouse (Mus musculus L.) using a long-term successive choice procedure involving
      six simultaneously available nest-boxes differing in size and shape. The subjects
      of the experiments were male and female individuals tested both singly and with
      their same-sex cagemates. The subjects were reared since birth in circular cages
      instead of the standard rectangular ones used in previous experiments. The
      preferences shown by circular-cage reared males in establishing their nest tended
      to be shape-linked, the rectangular being preferred to the square and circular
      nest-boxes of both sizes tested. Individuals used shape as the main choice
      criterion, whereas litters more often took smallness of size into account. The
      animals' choice of nest-box does not seem to be particularly gender-dependent,
      since no significant differences between the sexes were found in this respect.
      The order and number of visits recorded during the initial exploratory phase (the
      first 30 min) of the choice process indicated that size was the most frequent
      feature of the nest-boxes to be taken into account, which could simply be
      explained by the fact that larger nest-boxes are more likely to be encountered
      than small ones. On the other hand, the animals tested as a group explored the
      nest-boxes much more than those tested individually. The discussion deals mainly
      with gender-related and social spatial behaviours in rodents. 

PMID- 24924868
TI  - Operant-Pavlovian interactions: Ratio-schedules and the effects of the duration
      and location of a stimulus preceding response-independent food.
AB  - Two groups of four pigeons were exposed to either a fixed-ratio or a random-ratio
      schedule of reinforcement. Presentation of stimuli which preceded response
      independent food delivery was then superimposed upon this operant baseline. The
      duration and the location of stimulus presentation were varied in different
      experimental conditions. Random-ratio schedules maintained higher response rates
      than fixed-ratio schedules. Response rates during presentation of the stimulus on
      the operant key exceeded response rates in the absence of stimulus presentation
      for the fixed-ratio subjects, but not for the random-ratio subjects. Similar
      observations were made when stimulus presentation occurred on a seperate stimulus
      key. During stimulus presentation on the stimulus key, response rates on the
      operant key were considerably higher for the random-ratio subjects than for the
      fixed-ratio subjects, especially during longer presentation of the stimulus (30
      sec). 

PMID- 24924869
TI  - Mimicry and crypsis - a behavioural approach to classification.
AB  - Mimetic strategies are characterized by interference in information processes,
      whereby certain signalreceivers are deceived by a mimic. The function of mimetic
      behaviour as well as of other behavioural patterns which have evolved is to
      satisfy the needs of the environment. Therefore it would seem justified to
      classify the phenomena of mimicry and crypsis on the basis of the aims which
      mimics have. Furthermore, several ethological ideas and terms of the organism
      environment-interrelationships (irrelevant and relevant environment;
      communicative and information environment) are investigated to find out whether
      they are suitable to characterize and define animal and plant imitations. There
      are at least three complexes of mimetic strategies: 

PMID- 24924870
TI  - Adult-young interaction in Mongolian gerbils (Meriones unguiculatus ) in relation
      to duration of separation, age and kinship.
AB  - Mated pairs of Mongolian gerbils were rejoined by two of their own young, of both
      sexes, after periods of separation starting when the young were four or seven
      weeks of age and lasting either one or four weeks. An additional group of young
      was separated from their parents when six weeks old, this time for two weeks. The
      occurrence of sniffing, opposition and pursuit behaviour between each adult and
      each young gerbils was noted over a period of one hour. Our experiments showed
      differences in the behaviour of parents in relation to the period of isolation.
      Sniffing decreased and agonistic behaviour increased as the duration of
      separation increased. The duration of separation was of greater importance than
      age when separated. In the second part of the study, mated pairs were confronted
      with two unrelated young gerbils of both sexes, aged 5, 8 or 11 weeks, separated
      from their parents for respectively 1, 2 and 4 weeks. Similar experiments were
      carried out with groups of young of the same age, separated from their parents
      for one hour, and tested either with their parents or with unrelated mated pairs.
      Analysis of the experiments confirmed that interaction between adults and young
      depended more on the duration of separation than on age. Kinship resulted in less
      sniffing of both types of young by the adult female during the one hour
      separation experiments. In the course of these experiments, pursuit and
      opposition were almost totally absent. In our experiments, the determinant factor
      of adult-young relationship was the development of the young withdrawn from the
      influence of parents rather than age or Kinship. 

PMID- 24924871
TI  - Imitation learning in budgerigars: Dawson and Foss (1965) revisited.
AB  - Dawson and Foss (1985) have reported that each of five naive budgerigars
      (Melopsittacus undulatus ) after watching a demonstrator budgerigar use one of
      three different methods of opening a covered food dish, used the same method as
      its respective demonstrator to uncover its own food fish. Our first attempt to
      replicate Dawson and Foss' experiment was unsuccessful and revealed a number of
      sources of ambiguity in their methods. Modified procedures, removing these
      ambiguities, produced results confirming those of Dawson and Foss. However,
      although observer budgies exhibited a significant tendency to use the same method
      to uncover a food dish as did their respective demonstrators, the effect was both
      of brief duration and marginal significance. This relative fragility of the
      Dawson and Foss' (1965) finding renders it unsuitable as a model system for
      exploring the phenomenon of imitation learning. 

PMID- 24924872
TI  - Shadow of domestic violence and extramarital sex cohesive with spousal
      communication among males in Nepal.
AB  - BACKGROUND: Public health and human right issues are challenging in low and
      middle income countries. The main objectives of this paper were to determine the
      prevalence and factors associated with domestic violence, extramarital sex, and
      spousal communication among male. METHODS: A cross-sectional study among 2466
      married males in Kathmandu, Nepal was conducted using random sampling method.
      Adjusted odds ratios (AORs) and 95% confidence intervals (CI) of associated
      factors were estimated by stepwise backward likelihood ratio method. RESULTS:
      Prevalence of domestic violence was 63.14% (95% CI 61.20-65.05), extramarital sex
      was 32.12% (95% CI 30.27-34.00), and spousal communication was 48.87% (95% CI
      46.85-50.90). Nearly one in five male (18.20%) had not used condom during
      extramarital sex.Interestingly, male who had more than three or equal children
      were less likely to have perpetrated domestic violence compared with those who
      had less children. Older male aged 25 and above were more likely (AORs = 1.55,
      95% CI 1.19-2.03) to have extramarital sex compared with male aged 24 or below.
      Those male who had studied secondary or higher level of education were less
      likely to have extramarital sex compared to those who had primary level or no
      education. Male who had higher income were more likely to have spousal
      communication compared to those who had less income. Surprisingly, those male who
      had extramarital sex were less likely to have spousal communication compared with
      those was not involved in extramarital sex. CONCLUSION: Practice of domestic
      violence and extramarital sex is quite common among married male in Nepal, where
      spousal communication is sparse. These findings can be used to advocate for
      immediate attention and activities needs to be endorsed by policymakers and
      programmers.

PMID- 24924873
TI  - Loss of E-Cadherin expression is associated with a poor prognosis in stage III
      colorectal cancer.
AB  - PURPOSE: The epithelial-mesenchymal transition (EMT) is known to be associated
      with tumor progression, invasion and metastasis in colorectal cancer (CRC).
      MATERIALS AND METHODS: Tissue samples obtained from 409 patients with stage III
      CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the
      expression levels of E-cadherin, fibronectin, vimentin and alpha-smooth muscle
      actin (SMA). RESULTS: Among the 409 patients, 402 cases (98.3%) showed positive E
      cadherin expression. Positive E-cadherin expression was associated with well or
      moderately differentiated cell types and a stable microsatellite status. In
      multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p
      = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048),
      positive perineural invasion (p = 0.002) and negative E-cadherin expression (p =
      0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors
      affecting disease-free survival. The declining E-cadherin expression was
      associated with a poor outcome in terms of overall survival in univariate (p =
      0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI
      = 0.539-7.296). Fibronectin, vimentin and alpha-SMA were of no prognostic value
      in this study. CONCLUSION: The expression pattern of EMT markers in stage III CRC
      suggests that declining E-cadherin expression is a possible immunohistochemical
      predictor of patient prognosis.

PMID- 24924874
TI  - Modifying the risk associated with an impulsive temperament: a prospective study
      of drug dependence treatment.
AB  - The evidence linking the personality trait of impulsivity and substance misuse is
      well established. Importantly, impulsivity not only predicts substance misuse
      problems but has an association with duration in treatment, likelihood of
      completing treatment and time to relapse. Treatment that focuses on increasing
      awareness and acceptance of thoughts and emotions may potentially address
      impulsive behaviour and in this respect improve treatment outcomes for substance
      misuse. The current paper investigated the relationship between the facet of
      impulsivity that taps into poor inhibitory control and treatment outcome. In
      addition, there was a specific focus on ascertaining the impact of an increase in
      awareness and attentional control measured in 144 adult substance users receiving
      treatment in a residential therapeutic community. Impulsivity predicted poorer
      treatment outcome (measured as drug use severity). Increases in awareness and
      acceptance of emotions and thoughts during treatment were related to better
      outcome although this was not associated with baseline levels of impulsivity.
      Clinical and theoretical implications are discussed. 

PMID- 24924876
TI  - A case-control study on red meat consumption and risk of stroke among a group of
      Iranian adults.
AB  - OBJECTIVE: We aimed to examine the association between red meat consumption and
      stroke in a group of Iranian adults. DESIGN: A hospital-based case-control study.
      SETTING: The study included stroke patients and hospital-based controls. Usual
      dietary intakes of participants were assessed by means of a validated 168-item
      semi-quantitative FFQ. Total red meat consumption was calculated by summing up
      the consumption of red, processed and visceral meats. SUBJECTS: One hundred and
      ninety-five cases were stroke patients hospitalized in the neurology ward and 195
      controls were recruited from patients hospitalized in other wards with no history
      of cerebrovascular diseases or neurological disorders. RESULTS: Participants with
      stroke were older, more likely to be male and less likely to be obese.
      Individuals in the highest tertile of red meat intake were 119 % more likely to
      have stroke (OR=2.19; 95% CI 1.33, 3.60) compared with those in the lowest
      tertile. After controlling for age, sex and total energy intake, the association
      between red meat consumption and stroke was strengthened (OR=2.72; 95% CI 1.53,
      4.83). This association remained significant even after further controlling for
      physical activity and smoking as well as dietary intakes. Additional adjustments
      for BMI, diabetes, hypertension and hyperlipidaemia did not influence the
      association significantly (OR=2.51; 95 % CI 1.19, 5.09). CONCLUSIONS: Consumption
      of red meat was associated with greater odds of having stroke in a group of
      Iranian adults.

PMID- 24924875
TI  - A novel manipulation method of human body ownership using an fMRI-compatible
      master-slave system.
AB  - Bodily self-consciousness has become an important topic in cognitive neuroscience
      aiming to understand how the brain creates a unified sensation of the self in a
      body. Specifically, full body illusion (FBI) in which changes in bodily self
      consciousness are experimentally introduced by using visual-tactile stimulation
      has led to improve understanding of these mechanisms. This paper introduces a
      novel approach to the classic FBI paradigm using a robotic master-slave system
      which allows us to examine interactions between action and the sense of body
      ownership in behavioral and MRI experiments. In the proposed approach, the use of
      the robotic master-slave system enables unique stimulation in which experimental
      participants can administer tactile cues on their own back using active self
      touch. This active self-touch has never been employed in FBI experiments and it
      allows to test the role of sensorimotor integration and agency (the feeling of
      control over our actions) in FBI paradigms. The objective of this study is to
      propose a robotic-haptic platform allowing a new FBI paradigm including the
      active self-touch in MRI environments. This paper, first, describes the design
      concept and the performance of the prototype device in the fMRI environment (for
      3T and 7T MRI scanners). In addition, the prototype device is applied to a
      classic FBI experiment, and we verify that the use of the prototype device
      succeeded in inducing the FBI. These results indicate that the proposed approach
      has a potential to drive advances in our understanding of human body ownership
      and agency by allowing novel manipulation and paradigms. 

PMID- 24924877
TI  - Invasive candidiasis in low birth weight preterm infants: risk factors, clinical
      course and outcome in a prospective multicenter study of cases and their matched
      controls.
AB  - BACKGROUND: This multicenter prospective study of invasive candidiasis (IC) was
      carried out to determine the risk factors for, incidence of, clinical and
      laboratory features, treatment and outcome of IC in infants of birth weight <1250
      g. METHODS: Neonates <1250 g with IC and their matched controls (2:1) were
      followed longitudinally and descriptive analysis was performed. Survivors
      underwent neurodevelopmental assessment at 18 to 24 months corrected age.
      Neurodevelopmental impairment (NDI) was defined as blindness, deafness, moderate
      to severe cerebral palsy, or a score <70 on the Bayley Scales of Infant
      Development 2nd edition. Multivariable analyses were performed to determine risk
      factors for IC and predictors of mortality and NDI. RESULTS: Cumulative incidence
      rates of IC were 4.2%, 2.2% and 1.5% for birth-weight categories <750 g, <1000 g,
      <1500 g, respectively. Forty nine infants with IC and 90 controls were enrolled.
      Necrotizing enterocolitis (NEC) was the only independent risk factor for IC
      (p=0.03). CNS candidiasis occurred in 50% of evaluated infants, while congenital
      candidiasis occurred in 31%. Infants with CNS candidiasis had a higher mortality
      rate (57%) and incidence of deafness (50%) than the overall cohort of infants
      with IC. NDI (56% vs. 33%; p=0.017) and death (45% vs. 7%; p=0.0001) were more
      likely in cases than in controls, respectively. IC survivors were more likely to
      be deaf (28% vs. 7%; p=0.01). IC independently predicted mortality (p=0.0004) and
      NDI (p=0.018). CONCLUSION: IC occurred in 1.5% of VLBW infants. Preceding NEC
      increased the risk of developing IC. CNS candidiasis is under-investigated and
      difficult to diagnose, but portends a very poor outcome. Mortality, deafness and
      NDI were independently significantly increased in infants with IC compared to
      matched controls.

PMID- 24924878
TI  - Birth weight and neonatal adiposity prediction using fractional limb volume
      obtained with 3D ultrasound.
AB  - INTRODUCTION: The objective of this investigation was to study fetal thigh volume
      throughout gestation and explore its correlation with birth weight and neonatal
      body composition. This novel technique may improve birth weight prediction and
      lead to improved detection rates for fetal growth restriction. MATERIALS AND
      METHODS: Fractional thigh volume (TVol) using 3D ultrasound, fetal biometry and
      soft tissue thickness were studied longitudinally in 42 mother-infant pairs. The
      percentages of neonatal body fat, fat mass and fat-free mass were determined
      using air displacement plethysmography. Correlation and linear regression
      analyses were performed. RESULTS: Linear regression analysis showed an
      association between TVol and birth weight. TVol at 33 weeks was also associated
      with neonatal fat-free mass. There was no correlation between TVol and neonatal
      fat mass. Abdominal circumference, estimated fetal weight (EFW) and EFW centile
      showed consistent correlations with birth weight. Thigh volume demonstrated an
      additional independent contribution to birth weight prediction when added to the
      EFW centile from the 38-week scan (p = 0.03). CONCLUSION: Fractional TVol
      performed at 33 weeks gestation is correlated with birth weight and neonatal lean
      body mass. This screening test may highlight those at risk of fetal growth
      restriction or macrosomia.

PMID- 24924880
TI  - [Roles of environmental factors in the pathogenesis of bronchial asthma].

PMID- 24924879
TI  - [Paying greater attention to the studies of disease burden of bronchial asthma].

PMID- 24924881
TI  - [Status of tiotropium bromide in the treatment of bronchial asthma].

PMID- 24924882
TI  - [Risk factors of bronchial asthma among people aged over 14 years in China].
AB  - OBJECTIVE: To survey the risk factors of asthma among the people aged over 14
      years in China. METHODS: Home visits for completing epidemiological
      questionnaires in accordance with stratified cluster random sampling survey were
      conducted in 8 provinces (cities) of China residents aged over 14 years from
      February 2010 to August 2011. Asthma was diagnosed based upon case history,
      clinical signs and lung function test. The SPSS 12.0 software was used for
      statistic analyses for the epidemiological status of asthma. RESULTS: Sampling
      population was composed of 180 099 subjects. Among 164 215 valid questionnaires,
      there were 79 692 males and 84 523 females, 2 034 had asthma. The overall
      prevalence rate was 1.2% (2 034/164 215). Correlation analyses showed that the
      risk factors were smoking (OR = 1.697, 95%CI: 1.547-1.861), breast feeding (OR =
      0.801, 95%CI: 0.670-0.959), genetics (OR & 95%CI >1, asthma (OR = 10.440, 95%CI:
      8.991-12.112)), complications (OR & 95%CI >1), body mass index (compared with
      normal weight, overweight (OR = 1.360, 95%CI: 1.212-1.531), obesity (OR = 10.631,
      95%CI: 9.570-11.801)) and petting (OR & 95%CI >1). CONCLUSION: Among Chinese
      asthmatics aged over 14, their risk factors include host (genetics & obesity) and
      environmental (smoking, breastfeeding, complications & pets) factors.

PMID- 24924883
TI  - [Study on dynamic changes of airway hyperresponsiveness in children with cough
      variant asthma].
AB  - OBJECTIVE: To explore the dynamic changes of airway hyperresponsiveness (AHR) in
      children with cough variant asthma (CVA). METHODS: A prospective observational
      study was conducted at the Children's Hospital of Soochow University from April
      2012 to March 2013. A total of 36 patients were diagnosed as CVA. According to
      the integral dose of histamine resulting in a 20% (PD20) fall in forced
      expiratory volume in 1 s (FEV1), the severity of CVA was graded. Corresponding
      treatment was administered and the dynamic changes of airway hyperresponsiveness
      were followed for 0, 1 and 6 months. RESULTS: Among them, 14 patients suffered
      from CVA only while another 22 cases had CVA plus upper airway cough syndrome
      (UACS). PD20 of CVA and CVA+UACS groups were (0.46 +/- 0.26) and (0.58 +/- 0.34)
      mg respectively. No statistically significance existed between two groups (t = 
      0.880, P > 0.05). According to the value of PD20, AHR in CVA patients was
      classified into four degrees of severe, moderate, mild and very mild. Initially
      there were moderate (n = 8), mild (n = 21) and very mild (n = 5). At 1 month
      follow-up, moderate (n = 1), mild (n = 28) and borderline (n = 7); At 6 month,
      moderate (n = 2), mild (n = 20) and very mild (n = 7). And 4 cases turned
      negative and another 3 cases became lost. Cough symptom score and PD20 showed no
      significant correlation (r = -0.086, P > 0.05). CONCLUSIONS: AHR in CVA patients
      is predominantly mild and very mild. And it decreases rapidly mostly during
      initial treatment phase. The proportion of conversion from CVA into negative and
      typical bronchial asthma is relatively low.

PMID- 24924884
TI  - [Mechanism of signal molecule high mobility group box protein 1 mediated by Toll
      like receptor 2 in murine asthma].
AB  - OBJECTIVE: To explore the role and mechanism of signal molecule high mobility
      group box protein 1 (HMGB1) mediated by Toll-like receptor 2 (TLR2) in a murine
      asthma model. METHODS: Fourteen specific pathogen free (SPF) female C57 and TLR2(
      /-) mice each were randomly divided into 4 groups of C57 control, C57 asthma,
      TLR2(-/-) control and TLR2(-/-) asthma (n = 7 each). The animals were sensitized
      and challenged with ovalbumin (OVA) for asthmatic modeling. The same amount of
      normal saline was used in the control group. The supernatant of bronchoalveolar
      lavage fluid (BALF) was collected for detecting the level of HMGB1 by enzyme
      linked immunosorbent assay (ELISA). And the expression of HMGB1 in lung tissue
      was detected by Western blot and immunohistochemistry. RESULTS: Asthmatic murine
      model was successfully established. The level of HMGB1 in the BALF of C57 asthma
      group was significantly higher than that in C57 control, TLR2(-/-) asthma and
      TLR2(-/-) control groups ((59.0 +/- 13.9) vs (42.3 +/- 1.6), (47.5 +/- 2.3),
      (42.4 +/- 1.4) ng/L; P = 0.001, 0.001, 0.037) . The results of
      immunohistochemistry showed that the marker of HMGB1 in lung tissue was less than
      those in the C57 control and TLR2(-/-) control groups. However, the C57 asthma
      and TLR2(-/-) asthma groups were obviously more and they were located in airway
      epithelium. Western blot showed that the expression of HMGB1 was significantly
      higher in C57 asthma group than that in the C57 control, TLR2(-/-) asthma and
      TLR2(-/-) control groups (0.92 +/- 0.29 vs 0.18 +/- 0.09, 0.31 +/- 0.16, 0.21 +/-
      0.14; P = 0.007, 0.022, 0.009). CONCLUSIONS: HMGB1 promotes the airway
      inflammation mediated by TLR2. And it may participate in the pathogenesis of
      asthma.

PMID- 24924885
TI  - [Sequence analyses of HIRA gene 3'UTR region and related microRNA].
AB  - OBJECTIVE: To explore the HIRA gene sequences of 3'UTR region and elucidate the
      role of 3'UTR region of HIRA gene in the pathogenesis of tetralogy of Fallot
      (TOF). METHODS: Patients of TOF were confirmed by cardiac catheterization or
      surgery between April 2007 and December 2012 at our hospital. Mutations and
      single nucleotide polymorphisms (SNPs) were screened in 278 unrelated probands
      with isolated TOF and 515 controls. Target Scan was used to predict micro RNAs
      with possible combinations with 3'UTR region of HIRA gene. Dual-luciferase assay
      and real-time PCR were performed to detect the inhibition activity of micro RNAs
      on target genes. And chi(2) and t tests were used to analyze the results.
      RESULTS: Statistically significant change occurred in the alleleic frequencies of
      existing SNPs (rs:117447448) between TOF patients and control group (11.5%
      (32/278) vs 4.9% (25/515), P = 0.001) . The combining site of miR328 was
      predicted to be 10 bp upstream of SNP site. MiR328 was expressed in heart and it
      was related with myocardial infarction and atrial fibrillation. Dual-luciferase
      assay showed a decreased level of luciferase after co-transfection with miR328
      (0.012 5 +/- 0.000 6 vs 0.019 6 +/- 0.003 8, P = 0.034). So was the expression of
      HIRA (1.039 6 +/- 0.077 2 vs 1.608 7 +/- 0.274 9, P = 0.037). However, the
      luciferase level was not affected by SNP (rs:117447448) (P = 0.380). CONCLUSIONS:
      The SNP (rs:117447448) of 3'UTR region of HIRA gene is related with TOF. HIRA is
      the target gene of miR328. Although SNP (rs:117447448) is not a major site of
      target gene HIRA for micro RNA328, it provides an important clue to in-depth
      studies of 3'UTR region of HIRA gene in the pathogenesis of TOF.

PMID- 24924886
TI  - [Mutation analyses and prenatal diagnosis in two families of X linked severe
      combined immunodeficiency caused by IL2RG gene novel mutation].
AB  - OBJECTIVE: To evaluate the diagnostic feasibility of mutation analysis and
      prenatal genetic diagnosis genetic analysis of IL2RG gene in two families with a
      birth history of X-linked severe combined immunodeficiency (X-SCID). METHODS:
      Blood samples of a male infant patient of X-SCID and his mother in family 1 and
      the parents of another deceased child with X-SCID in family 2 from January 2012
      to February 2013 were collected.Eight exons comprising IL2RG open reading frame
      and their exon/intron boundaries were analyzed by bi-directional direct
      sequencing of polymerase chain reaction (PCR) products. Prenatal genetic
      diagnoses were performed by chorionic villus sampling after the genotypes of
      maternal probands were identified in family 1. RESULTS: Two mutations of IL2RG
      gene were identified in these two families. The c.361-363delGAG (p.E121del)
      mutation was identified in family 1. The c.510-511insGAACT (p.W173X) mutation
      appeared in family 2. The two mutations of c.361-363delGAG (p.E121del) and c.510
      511insGAACT (p.W173X) were novel. The two novel mutations were absent in 100
      normal controls. The pregnancy in family 1 continued and the infant showed no
      symptom of X-SCID at 1 year after birth. The aunt (II-3) of proband in family 1
      was not a carrier. The female fetus in family 1 had no mutation. CONCLUSIONS: Two
      novel mutations of c.361-363delGAG (p.E121del) and c.510-511insGAACT (p.W173X) in
      IL2RG gene may be a major cause of disease in two families with X-SCID. And
      direct sequencing of IL2RG gene provides genetic counseling, prenatal diagnosis
      and carrier screening for families with X-SCID.

PMID- 24924887
TI  - [Predictors and outcomes of recurrence after resection of colorectal liver
      metastases].
AB  - OBJECTIVE: To explore the outcomes of different recurrence patterns and
      recurrence-related factors after hepatectomy in patients with colorectal liver
      metastases (CRLM). METHODS: The outcomes of different recurrence patterns and
      recurrence-related factors for surgical resection of CRLMs was reviewed
      retrospectively. RESULTS: A total of 152 postoperative recurrent cases were
      included between 2000 and 2013. The median overall survival was 28.9 months and 5
      year survival 22.1% for the entire group. The median disease-free survival was
      7.6 months. Among them, 60 patients had disease recurrence within 6 months after
      hepatectomy (early recurrence) and their median overall survival was 19.4 months
      versus 35.1 months (n = 92) for those with a disease-free interval of over 6
      months (P = 0.000).Repeat resection was associated with better outcomes, but
      different patterns of recurrence were not. Lymph node metastases of primary
      tumor, number of metastases and efficacy of neo-adjuvant chemotherapy (NACT) were
      independently associated with recurrence. CONCLUSIONS: Recurrence after
      hepatectomy of CRLMs is affected by lymph node metastases of primary tumor,
      number of metastases and efficacy of NACT. Additional survival advantage may be
      achieved by resection of recurrent disease.

PMID- 24924888
TI  - [Prognostic factor analysis of surgical treatment in patients with rectal
      neuroendocrine neoplasms].
AB  - OBJECTIVE: To analyze the prognostic factors and long-term surgical efficacies of
      rectal neuroendocrine neoplasm (NEN). METHODS: The clinical and pathological data
      of 141 patients with rectal NENs treated between January 1999 and November 2012
      were retrospectively analyzed. The Kaplan-Meier method was used to calculate
      survival time and Cox regression to analyze the clinicopathological factors
      correlating with patient prognosis. RESULTS: The overall 1, 3 and 5-year survival
      rates were 95.4%, 87.0% and 82.8% respectively. According to the criteria of WHO
      classification (2010) and staging system about rectal NEN, there were grade 1
      (G1) (n = 76, 79.2%), grade 2 (G2) (n = 12, 12.5%), neuroendocrine carcinoma
      (NEC) (n = 7, 7.3%) and mixed adenoneuroendocrine carcinoma (n = 1, 1.0%), the 1,
      3 and 5-year survival rates were 98.6%, 43.7%,0% and 100.0% respectively. There
      were stage I (n = 71, 74.0%) , stage II (n = 5, 5.2%), stage III (n = 12, 12.5%)
      and stage IV (n = 8, 8.3%) . The 1, 3 and 5-year survival rates were 97.7%,
      75.0%, 57.1% and 25.0% respectively.Univariate analysis showed that tumor
      diameter, histological grade, lymph node metastasis, distant metastasis, radical
      surgery and muscular layer invasion significantly affected the postoperative
      survival. And Cox multivariate analysis indicated that tumor diameter and
      histological grade were independent prognostic factors. CONCLUSIONS: Rectal NENs
      vary significantly in their prognoses.However, radical surgery offers
      satisfactory long-term survival rates. An optimal surgical approach should be
      selected based on tumor size. And more radical surgery should be performed for
      neuroendocrine tumors >2 cm.

PMID- 24924889
TI  - [Expression of CD133 in primary retroperitoneal leiomyosarcoma and its
      relationship with Ki-67].
AB  - OBJECTIVE: To explore the correlation between CD133 and proliferative marker Ki
      67 in primary retroperitoneal leiomyosarcoma and evaluate their prognostic
      values. METHODS: A total of 50 primary retroperitoneal leiomyosarcoma samples
      were collected at our hospital from January 2000 to December 2012. There were 9
      males and 41 females. All samples were analyzed for CD133 and Ki-67 protein
      expression by PV6000 immunohistochemistry. Their median age was 49 (27-75) years.
      All cases were successfully followed up. RESULTS: CD133 expression was detected
      in 74.00% (37/50) of primary retroperitoneal leiomyosarcoma samples. The CD133
      positive rates of histological grades I & II primary leiomyosarcoma were 7/13 and
      76.70% (23/30) respectively. All grade III samples (n = 7) were CD133 positive.
      And the expression of CD133 had a positive correlation with tumor size, mitotic
      counts and histological grade (chi(2) = 4.925, 4.525, 10.080; P = 0.026, 0.033,
      0.013). The survival time of CD133-positive patients with M (Q1, Q3) was 32 (17,
      56) months versus 44 (26, 65) months for those negative ones. The expression of
      Ki-67 was detected in 84.00% (42/50) of primary retroperitoneal leiomyosarcoma
      samples and its expression showed a positive correlation with mitotic counts. The
      expressions of CD133 and Ki-67 were positively correlated in primary
      retroperitoneal leiomyosarcomas (P = 0.009). Log-rank test showed that positive
      expressions of CD133 and Ki-67 and 5-year patient survival rate were correlated
      (P = 0.021, 0.049). Multivariate analysis showed that CD133 and mitotic counts
      were independent prognostic indicators for primary retroperitoneal
      leiomyosarcomas (HR = 2.040, 2.422; P = 0.000, 0.018). CONCLUSIONS: CD133 plays
      an important role in the progression of primary retroperitoneal leiomyosarcomas
      so that it may be used as a marker for patient prognosis. Combined detection of
      CD133 and Ki-67 has a prognostic value in patients with primary retroperitoneal
      leiomyosarcoma.

PMID- 24924890
TI  - [Infection rate of human papillomavirus and its association with laryngeal cancer
      in Chinese: a meta-analysis].
AB  - OBJECTIVE: To systematically explore the prevalence of human papillomavirus (HPV)
      in laryngeal cancer (LC) in Chinese and evaluate the association between HPV
      infection and laryngeal cancer risk. METHODS: The databases both in English and
      Chinese were searched. And the studies met the inclusion criteria were included.
      The prevalence of HPV in LC group and in subgroups, stratified by publishing
      years and sample storage methods, were analyzed by the R 3.0 software
      respectively. The cancer risk of HPV infection was estimated by odds ratio (OR)
      generated by comparisons with the control group. RESULTS: The overall prevalence
      of HPV was 32% [95% confidence interval (CI): 22%-44%] and the prevalence of high
      risk HPV-16/18 and low-risk HPV-6/11 was 30% (95%CI: 24%-37%) and 12% (95%CI: 9%
      17%) respectively in Chinese LC patients. The HPV-16/18 infection rate was 24%
      (95%CI: 15%-35%) in the subgroup between 1992 and 2000 and 32% (95%CI: 24%-41%)
      in the subgroup from 2001 to 2012 respectively. And no significant difference
      existed between two subgroups (P = 0.07). The HPV-16/18 infection rate in
      formalin-fixed paraffin-embedded sample cohort was not significantly different
      from the fresh-frozen sample cohort [31% (95%CI: 24%-39%) and 28% (95%CI: 18%
      42%); P = 0.06]. Meta-analysis showed the overall HPV infection rate in the LC
      group was significantly higher than in the control group (OR = 15.87 (95%CI: 9.25
      27.24); P < 0.01). Moreover, as compared with the control group, the patients in
      the LC group had a higher infection rate of HPV-16/18 (OR = 8.07 (95%CI: 5.67
      11.48); P < 0.01). CONCLUSIONS: HPV infection rates in Chinese LC patients stay
      at a relatively high level and tend to increase over time. And HPV infection may
      increase LC risk in Chinese.

PMID- 24924891
TI  - [Diagnosis and surgical treatment of pulmonary artery sarcoma].
AB  - OBJECTIVE: To characterize the differential diagnostic characteristics and the
      surgical treatment efficacy of pulmonary artery sarcoma (PAS). METHODS: From
      November 2001 to January 2014, 19 PAS patients were diagnosed and 14 of them
      underwent surgery at Beijing Anzhen Hospital. And their data were retrospectively
      reviewed. RESULTS: All 19 patients underwent pulmonary artery computed tomography
      angiography (CTA) scan. All showed a filling defect within the lumen of pulmonary
      artery with a sign of wall eclipsing. And 14 of them had pulmonary artery sarcoma
      confirmed through postoperative histopathological examination while another 5
      patients were confirmed to have FDG abnormal high intake mass shadow on Positron
      emission tomography-computed tomography (PET-CT) scan. Fourteen patients
      underwent surgery, including pulmonary endarterectomy (n = 12) and pneumonectomy
      (n = 2), and another five had no indication for operation and died shortly. No
      perioperative death occurred for surgical patients. Five non-surgical patients
      survived (20.3 +/- 11.2) days after discharge. And 14 postoperative patients
      survived (16.8 +/- 3.8) months. The difference between two groups reached
      statistical significance (P = 0.000). The survival difference between two
      surgical procedures and between two pathological classifications did not reach
      statistical significance. Nine patients did not while another 5 received adjuvant
      radiotherapy and chemotherapy. Their average survivals were (12.3 +/- 3.2) and
      (22.8 +/- 4.3) months respectively. And the inter-group difference reached
      statistical significance (P = 0.000). CONCLUSIONS: The sign of wall eclipsing on
      pulmonary artery CTA scan is pathognomonic for PAS. Radical surgical resection
      provides a longer survival than non-surgery and adjuvant chemotherapy may further
      extend survival.

PMID- 24924892
TI  - [Correlation of serum adropin level with coronary artery disease].
AB  - OBJECTIVE: To explore the correlation of serum adropin level with coronary artery
      disease (CAD). METHODS: According to coronary angiography, 356 consecutive
      patients with chest complaints from January 2011 to July 2012 were divided into 2
      groups of CAD (n = 264, with CAD) and control (n = 92, without CAD). The serum
      adropin level and other CAD related metabolic parameters were measured and SYNTAX
      score was calculated. RESULTS: Serum adropin level was significantly lower in
      group CAD than that in control group ((56 +/- 15) vs (83 +/- 10) ng/L, P <
      0.01).Serum adropin levels in high, mild, low SYNTAX score group were (60 +/-
      22),(56 +/- 12),(54 +/- 10) ng/L respectively, and there was no significant
      difference among 3 groups(P = 0.116). Multivariate regression analysis revealed
      that adropin was an independent risk factor for CAD (OR = 0.849, 95%CI:0.817
      0.882, P < 0.01). CONCLUSIONS: Lower serum adropin level is significantly
      associated with CAD. Thus it indicates a possible role of adropin in the
      prevention of CAD.

PMID- 24924893
TI  - [Clinical observation of DECP combination chemotherapy for relapsing and
      refractory multiple myeloma patients with extramedullary plasmacytomas].
AB  - OBJECTIVE: To explore the clinical effect and toxicity of (cisplatin, etoposide,
      ifosfamide & dexamethasone) DECP combination chemotherapy in the treatment of
      relapsing and refractory multiple myeloma (MM) with extramedullary plasmacytomas.
      METHODS: A total of 20 relapsed and refractory MM patients with extramedullary
      plasmacytomas treated with DECP regimen from May 2005 to May 2013 were analyzed
      retrospectively. DECP protocols included cisplatin 20 mg/m(2), Day 1-3; etoposide
      100 mg/d,Day 1-3; ifosfamide 500 mg.m(-2).d(-1), Day 1-4; dexamethasone 20 mg/d,
      Day 1-4. Efficacy was evaluated after 2 therapeutic cycles. RESULTS: After 2
      therapeutic cycles, the objective response rate (ORR) was 55% (11/20). After 3
      therapeutic cycles, the ORR was 7/12.Seven patients completed 4 cycles with an
      ORR of 4/7. Two patients had finished 6 cycles and continued to maintain partial
      remission. The most common adverse events included gastrointestinal reaction and
      myelosuppression. The median follow-up time was 30 (12-80) months. The median
      time of overall survival (OS) was 30 (9-121) months. The 1-year OS was 73%, 2
      year OS 28% and 3-year OS 21%. CONCLUSION: The DECP chemotherapy is both
      effective and safe in the treatment of relapsed and refractory MM patients with
      extramedullary plasmacytomas.

PMID- 24924894
TI  - [Effects of adenosine on hMLH1 methylation of human colorectal cancer cells].
AB  - OBJECTIVE: To explore the effects of adenosine on hMLH1 methylation of human
      colorectal cancer cells. METHODS: The SW480 cells were treated with adenosine at
      the concentrations of 0, 1.5, 3.0, 4.5 mmol/L for 72 h. The hMLH1 methylation
      levels of CpG islands were detected by bisulfite sequencing polymerase chain
      reaction (BSP), hMLH1 mRNA expression levels by reverse transcription-polymerase
      chain reaction (RT-PCR), the expression levels of hMLH1 protein by Western blot
      and the apoptotic rates by flow cytometry (FCM). The cells were treated with
      adenosine at the concentrations of 0, 1.5, 3.0, 4.5 mmol/L for 24, 48, 72, 96 h.
      And their proliferation rates were detected by methyl thiazolyl tetrazolium
      (MTT). RESULTS: After a 72 h treatment of adenosine, the hMLH1 promoter
      methylation levels of 1.5, 3.0 and 4.5 mmol/L groups were 65% +/- 4%, 45% +/- 11%
      and 16% +/- 4% respectively and were all significantly lower than that of the
      control group (80% +/- 4%, all P < 0.01). The mRNA expression levels, hMLH1
      protein expression levels and apoptotic rates were all significantly higher than
      that of the control group (0.230 +/- 0.032, 0.359 +/- 0.029 and 0.570 +/- 0.019
      vs 0.079 +/- 0.010; 0.353 +/- 0.016, 0.654 +/- 0.018 and 0.854 +/- 0.014 vs 0.126
      +/- 0.016; 11.9% +/- 0.6%, 20.0% +/- 1.8% and 35.8% +/- 1.8% vs 3.9% +/- 1.4%,
      all P < 0.01). MTT showed that the proliferation rates of SW480 cells were lower
      than that of the control group and a time-dosage dependence existed (all P <
      0.05). CONCLUSION: Adenosine can reverse the abnormal methylation of hMLH1 CpG
      island and promote the expression of hMLH1 so as to restrain the proliferation
      and promote the apoptosis of colocectal cancer cells.

PMID- 24924895
TI  - [Effects of catalpol, L-shikonin and paeonol extracted from radix rehmanniae,
      radix arnebiae and cortex moutan on KGF-induced HaCaT cell proliferation].
AB  - OBJECTIVE: To explore the effects of Chinese herbal medicine radix rehmanniae,
      radix arnebiae and cortex moutan on the proliferation of HaCaT cells and explore
      their potential curative mechanisms. METHODS: The main monomers of catalpol, l
      shikonin and paeonol were extracted. And 10 ng/ml keratinocyte growth factor
      (KGF) was used to induce HaCaT cell to build an in vitro model of
      hyperproliferation of epidermal keratinocytes. CCK-8 assay and flow cytometry
      were applied to examine the effects of herbal monomers on cell proliferation and
      cell cycle. RESULTS: Both l-shikonin ( >= 10(-6) mol/L) and paeonol ( >= 1.88*10(
      4) mol/L) inhibited cell proliferation while catalpol ( >= 10(-6) mol/L) enhanced
      cell proliferation.L-shikonin ( >= 10(-6) mol/L) and paeonol ( >= 1.88*10(-4)
      mol/L) inhibited the HaCaT cell during S and G2M phases while catalpol ( >= 10(
      6) mol/L) enhanced HaCaT cell during S phase but not G2M phase. CONCLUSION: L
      shikonin and paeonol inhibits the proliferation of HaCaT cells while catalpol has
      opposite effects.

PMID- 24924896
TI  - [Activity of glial cells in trigeminal nervous system in rats with experimental
      pulpitis].
AB  - OBJECTIVE: To observe the activity change of astrocyte in related nucleus caused
      by acute pulpitis in rats. METHODS: Rat acute pulpitis model was induced by
      lipopolysaccharides (LPS). And, according to processing time, a total of 30 rats
      were divided into 5 groups of control, 6, 12, 24 and 48 h. Immunohistochemistry
      and Western blot were employed to detect the dynamic expression of glial
      fibrillary acidic protein (GFAP) in spinal nucleus of trigeminal nerve (Vc).
      RESULTS: The relative gray value of ipsilateral Vc GFAP expression in
      experimental groups was 153 +/- 11 at 12 h. And it significantly increased versus
      the control group (100 +/- 4)(P < 0.05). The relative gray value of GFAP was 198
      +/- 12 at 24 h and was 231 +/- 9 at 48 h. And they significantly increased versus
      the control group (both P < 0.01). Their expressions were time-dependent.
      CONCLUSION: In this acute pulpitis model, activated glial cells are probably
      involved in the processes of pulpitis and hyperalgesia.

PMID- 24924897
TI  - [Effects of transforming growth factor-beta1 gene silencing on the expression of
      vascular endothelial growth factor in human bladder cancer cell lines].
AB  - OBJECTIVE: To employ RNA interference technology to silence transforming growth
      factor-beta1 (TGF-beta1) gene to examine the gene silencing effects of RNAi on
      the expression of vascular endothelial growth factor (VEGF) in human bladder
      cancer cell lines (EJ). METHODS: The TGF-beta1 gene-specific siRNA expression
      vector was constructed. And the most efficiently suppressed target sequences were
      screened through reverse transcription-polymerase chain reaction (RT-PCR) and
      enzyme-linked immunosorbent assay (ELISA). The samples were divided into 3 groups
      of EJ, control (TGF-beta1) and recombinant plasmid (TGF-beta1 siRNA expression
      vector). And the expression level of VEGF protein was detected by Western blot.
      RESULTS: TGF-beta1 gene-specific siRNA expression vector was constructed
      successfully. TGF-beta1 relative mRNA expression was 0.92 +/- 0.19 and the
      protein expression level (50 +/- 6) pg/ml. The protein expression level of EJ
      group after transfection was (0.86 +/- 0.18) pg/ml, control group (1.15 +/- 0.29)
      pg/ml and recombinant plasmid group (0.45 +/- 0.16) pg/ml(both P < 0.05).
      CONCLUSIONS: An inhibition of TGF-beta1 gene down-regulates the expression of
      VEGF. And TGF-beta1 may regulate angiogenesis of bladder tumor through an
      induction of VEGF gene expression.

PMID- 24924898
TI  - Comment: Dietary glycemic load and stroke: what is needed for stable risk
      assessment?

PMID- 24924899
TI  - Dietary glycemic load and stroke: what is the need for stable risk assessment on
      stroke?

PMID- 24924900
TI  - Burn after feeding. An old uncoupler of oxidative phosphorylation is redesigned
      for the treatment of nonalcoholic fatty liver disease.
AB  - Uncoupling of oxidative phosphorylation (OXPHOS) in brown adipose tissue can be
      used by hibernating animals to produce heat at the expense of their fat mass. In
      a recent work, Dr Shulman et al. generated a liver-targeted derivative of the
      prototypical OXPHOS uncoupler 2,4-dinitrophenol that alleviated steatosis,
      hypertriglyceridemia and insulin resistance in several models of nonalcoholic
      fatty liver disease and type 2 diabetes.

PMID- 24924901
TI  - Variability in definitions of transaminase upper limit of the normal impacts the
      APRI performance as a biomarker of fibrosis in patients with chronic hepatitis C:
      "APRI c'est fini ?".
AB  - BACKGROUND: The aspartate aminotransferase platelet ratio index (APRI) is a
      validated, non-patented blood test for diagnosing fibrosis or cirrhosis in
      patients with chronic hepatitis C. We assess the impact of two limitations, the
      variability of the upper limit of normal for aspartate aminotransferase (AST-ULN)
      and the risk of overestimating fibrosis stage due to necroinflammatory activity.
      METHODS: The variability of AST-ULN was assessed by an overview of the literature
      and an assessment of AST-ULN in 2 control populations 7521 healthy volunteers and
      393 blood donors. We assessed the impact of AST-ULN variability on APRI
      performance for estimating fibrosis prevalence and on the Obuchowski measure
      using individual data of 1651 patients with APRI, FibroTest and biopsy. RESULTS:
      The overview, and the analysis of the control populations found that ULN-AST
      ranged from 26 to 49 IU/L according to gender, body mass index and serum
      cholesterol. When this AST-ULN variability was applied to the chronic hepatitis
      group, the prevalence of advanced fibrosis and cirrhosis as presumed by APRI
      varied (P<0.001) from 34.7% to 68.5%, and from 11.4% to 32.3%, respectively. This
      spectrum effect induced variability in APRI performance, which could be similar
      0.862 (if AST-ULN=26 IU/L) or lower 0.820 (AST-ULN>=30IU/L) than the stable
      FibroTest performance (0.867; P=0.35 and P<0.0001 respectively). When applied to
      18 acute hepatitis C patients, the rate of false positives of APRI varied from 0%
      to 61% due to AST-ULN. CONCLUSION: The AST-ULN variability is high highly
      associated with the variability of metabolic risk factors between the different
      control groups. This variability induces a spectrum effect, which could cause
      misleading interpretations of APRI performance for the staging of fibrosis,
      comparisons of APRI with other non-invasive tests, and estimates of false
      positive rate.

PMID- 24924902
TI  - A meta-analysis of cytokine-induced killer cells therapy in combination with
      minimally invasive treatment for hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVE: There was a continuing controversy on whether the
      adoptive transfusion of cytokine-induced killer cells (CIK) therapy should have
      been recommended to reduce the recurrence and metastasis of hepatocellular
      carcinoma (HCC) after minimally invasive therapy such as TACE (transarterial
      chemoembolization) or TACE plus RFA (radiofrequency ablation) treatment. The meta
      analysis was conducted to compare the effectiveness of CIK cells transfusion
      therapy combined with TACE or TACE plus RFA treatment with that of minimally
      invasive therapy alone. METHODS: Relevant studies were identified by electronic
      search using a combination of "hepatocellular carcinoma" and "cytokine-induced
      killer cells". Overall survival (OS) rates and recurrence-free survival (RFS)
      rates were compared as the major outcome measures. The meta-analysis was divided
      into two sub-studies (sub-study 1: CIK+TACE+RFA versus TACE+RFA; sub-study 2:
      CIK+TACE versus TACE) to avoid the risk of bias as we could. RESULTS: Meta
      analysis data suggested that CIK cells transfusion therapy combined with TACE
      plus RFA treatment was associated with higher 1-year RFS rate (odds ratio
      [OR]=2.46) and 1-year, 2-year OS rates (OR: 1-year=2.09; 3-year=2.16) than TACE
      plus RFA treatment alone in sub-study 1. For sub-study 2, there were significant
      differences between CIK+TACE group and TACE group for OS rates (OR: half
      year=3.29; 1-year=3.71; 2-year=7.37). CONCLUSION: CIK cells transfusion therapy
      truly showed a synergistic effect for HCC patients after minimally invasive
      treatment especially for a long-term survival.

PMID- 24924903
TI  - Liver biopsy in children 2014: who, whom, what, when, where, why?
AB  - Liver biopsy is the standard procedure for obtaining hepatic tissue for
      histopathological examination. The three major techniques are percutaneous,
      transvenous, and laparoscopic/open biopsy, with either cutting or suction
      needles. The indications for liver biopsy are shifting as knowledge of
      etiologies, non-invasive biomarker alternatives, and treatment options in
      paediatric liver disease expand. This mini-review presents specific indications,
      alternative approaches, methods, complications, and contraindications for
      paediatric liver biopsy. 

PMID- 24924904
TI  - Expression of epithelial cell adhesion molecule associated with elevated ductular
      reactions in hepatocellar carcinoma.
AB  - AIM: To evaluate the prognostic significance of the epithelial cell adhesion
      molecule (EpCAM) expression in HCC, the relationship between EpCAM with ductular
      reactions and other clinical features. METHODS: From 2001 to 2003, 106 HCC
      patients who underwent curative resection in Eastern Hepatobiliary Hospital were
      enrolled. The expression of EpCAM in tumoral tissues and ductular reactions in
      paired non-tumoral tissues was assessed by immunohistochemistry. EpCAM was
      evaluated with prognosis, ductular reactions and other clinical variables.
      RESULTS: HCC expressing high level of EpCAM showed more aggressively than usual
      progressed HCC. High EpCAM expression was associated with poor overall survival
      and recurrence free survival. (P=0.0005, 0.0019, respectively). A close
      association was found between tumoral EpCAM expression and peritumoral ductular
      reactions. Patients with high level of ductular reactions tended to have higher
      EpCAM expression than those with low level (P=0.016). CONCLUSION: HCC
      stratification by EpCAM may reflect different prognosis. EpCAM expression
      correlated with ductular reactions may be a result of unregulated activation and
      differentiation blockage of progenitor cells.

PMID- 24924905
TI  - Sexual differentiation of vertebrate reproductive organs. Preface.

PMID- 24924906
TI  - Interfacial mechanisms in active emulsions.
AB  - Active emulsions, i.e., emulsions whose droplets perform self-propelled motion,
      are of tremendous interest for mimicking collective phenomena in biological
      populations such as phytoplankton and bacterial colonies, but also for
      experimentally studying rheology, pattern formation, and phase transitions in
      systems far from thermal equilibrium. For fuelling such systems, molecular
      processes involving the surfactants which stabilize the emulsions are a
      straightforward concept. We outline and compare two different types of reactions,
      one which chemically modifies the surfactant molecules, the other which transfers
      them into a different colloidal state. While in the first case symmetry breaking
      follows a standard linear instability, the second case turns out to be more
      complex. Depending on the dissolution pathway, there is either an intrinsically
      nonlinear instability, or no symmetry breaking at all (and hence no locomotion). 

PMID- 24924907
TI  - Genomic and comparative genomic analyses of Rickettsia heilongjiangensis provide
      insight into its evolution and pathogenesis.
AB  - Rickettsia heilongjiangensis, the causative agent of far eastern spotted fever,
      is an obligate intracellular gram-negative bacterium that belongs to the spotted
      fever group rickettsiae. To understand the evolution and pathogenesis of R.
      heilongjiangensis, we analyzed its genome and compared it with other rickettsial
      genomes available in GenBank. The R. heilongjiangensis chromosome contains 1333
      genes, including 1297 protein coding genes and 36 RNA coding genes. The genome
      also contains 121 pseudogenes, 54 insertion sequences, and 39 tandem repeats.
      Sixteen genes encoding the major components of the type IV secretion systems were
      identified in the R. heilongjiangensis genome. In total, 37 beta-barrel outer
      membrane proteins were predicted in the genome, eight of which have been
      previously confirmed to be outer membrane proteins. In addition, 266 potential
      virulence factor genes, seven partially deleted antibiotic resistance genes, and
      a genomic island were identified in the genome. The codon usage in the genome is
      compatible with its low GC content, and the amino acid usage shows apparent bias.
      A comparative genomic analysis showed that R. heilongjiangensis and R. japonica
      share one unique fragment that may be a target sequence for a diagnostic assay.
      The orthologs of 37 genes of R. heilongjiangensis were found in pathogenic R.
      rickettsii str. Sheila Smith but not in non-pathogenic R. rickettsii str. Iowa,
      which may explain why R. heilongjiangensis is pathogenic. Pan-genome analysis
      showed that R. heilongjiangensis and 42 other rickettsiae strains share 693 core
      genes with a pan-genome size of 4837 genes. The pan-genome-based phylogeny showed
      that R. heilongjiangensis was closely related to R. japonica. 

PMID- 24924910
TI  - A new one-layer epididymovasostomy technique.
AB  - OBJECTIVES: To describe and evaluate the outcomes of a new epididymovasostomy
      technique. PATIENTS AND METHODS: Nine patients with obstructive azoospermia were
      treated at the Minia University Hospital using a new microsurgical bilateral
      epididymovasostomy technique. The technique involved the opening of a small
      window in the tunica of the epididymis, making an opening in the underneath
      epididymal tubule and keeping it open by fixing the edges of the epididymal
      opening to the edge of the epididymal tunica with four 10/0 nylon sutures. The
      abdominal cut end of the vas deferens was then anastomosed to the epididymal
      opening by suturing the epididymal tubule, fixed to its tunica in one layer, to
      the full thickness vas deferens. The main outcome measure was finding sperm in
      the ejaculate. RESULTS: Sperm was found in the ejaculate in six out of nine
      patients after our new, one-layer, epididymovasostomy technique. Mean +/- sd
      operating time was 176 +/- 23 min. CONCLUSIONS: This new, one-layer,
      epididymovasostomy technique provides a simple alternative method of
      epididymovasostomy, with reasonable outcomes. More cases and follow-up are needed
      to make meaningful comparisons with conventional epididymovasostomy.

PMID- 24924909
TI  - ZAP70 in B-CLL cells related to the expression in NK cells is a surrogate marker
      for mutational status.
AB  - The strongest prognostic factor in chronic B-cell lymphocytic leukemia (CLL) is
      the mutational status of the immunoglobulin heavy chain variable region (IGHV)
      genes. Determination of this mutational status is laborious and therefore not
      applied in routine diagnostics. A search for "surrogate markers" has been
      conducted over the past few years. One of the most promising surrogate markers is
      ZAP70, but standardization of the measurement of ZAP70 has proven to be
      difficult. Conventionally, ZAP70 expression in CLL cells is related to ZAP70
      expression in T cells. We propose a new method in which ZAP70 expression in NK
      cells is used as reference (new NK-MFI method). We have measured ZAP70 expression
      in samples of 45 previously untreated CLL patients. ZAP70 in CLL cells related to
      ZAP70 in NK cells correlated better to cytogenetic risk profile and mutational
      status than the conventional methods. Negativity of both ZAP70 (new NK-MFI
      method) and CD38 resulted in a probability of 90% for mutated IGHV genes. In
      conclusion, ZAP70 expression in CLL cells related to ZAP70 expression in NK cells
      is a better surrogate marker for mutational status than the conventional T cell
      related methods.

PMID- 24924911
TI  - One-year outcome of two different initial dosing regimens of intravitreal
      ranibizumab for myopic choroidal neovascularization.
AB  - PURPOSE: To evaluate and compare the 12-month outcomes of two different initial
      dosing regimens of intravitreal ranibizumab for myopic choroidal
      neovascularization (CNV). METHODS: We retrospectively reviewed the medical
      records of 46 consecutive, treatment-naive eyes which received intravitreal
      ranibizumab for subfoveal and juxtafoveal CNV secondary to pathologic myopia with
      a follow-up of 12 months. Two groups were created according to different initial
      dosing regimens: group 1 included 25 eyes treated by a single intravitreal
      injection; group 2 included 21 eyes treated by three consecutive monthly
      injections. Additional injections were performed if needed. Patients' demographic
      data, best-corrected visual acuity (BCVA), recurrence of CNV and total number of
      treatments were recorded and evaluated. RESULTS: There was no significant
      difference between two groups among baseline demographic data. At 12 months, the
      mean logMAR BCVA improved from 0.58 to 0.23 in group 1 and from 0.55 to 0.22 in
      group 2 (both p < 0.001; Wilcoxon signed-rank test). The mean logMAR BCVA at 12
      months did not differ significantly. The average number of injections was 2.32
      (SD 1.22) in group 1 and 3.57 (SD 1.12) in group 2 (p = 0.001; two-tailed t
      test). During the follow-up, 17 of 25 eyes in group 1 and 5 of 21 eyes in group 2
      received additional injections (p = 0.004). CONCLUSIONS: Similar visual
      improvement was achieved in both groups. Although the eyes with a loading dose of
      3 monthly injections required a higher number of total injections over 1 year,
      there was a much lower rate of retreatment needed.

PMID- 24924912
TI  - Comments on "Modified wind chill temperatures determined by a whole body
      thermoregulation model and human-based convective coefficients" by Ben Shabat,
      Shitzer and Fiala (2013) and "Facial convective heat exchange coefficients in
      cold and windy environments estimated from human experiments" by Ben Shabat and
      Shitzer (2012).
AB  - Ben Shabat et al. (Int J Biometeorol 56(4):639-51, 2013) present revised charts
      for wind chill equivalent temperatures (WCET) and facial skin temperatures (FST)
      that differ significantly from currently accepted charts. They credit these
      differences to their more sophisticated calculation model and to the human-based
      equation that it used for finding the convective heat transfer coefficient (Ben
      Shabat and Shitzer, Int J Biometeorol 56:639-651, 2012). Because a version of the
      simple model that was used to create the current charts accurately reproduces
      their results when it uses the human-based equation, the differences that they
      found must be entirely due to this equation. In deriving it, Ben Shabat and
      Shitzer assumed that all of the heat transfer from the surface of their
      cylindrical model was due to forced convection alone. Because several modes of
      heat transfer were occurring in the human experiments they were attempting to
      simulate, notably radiation, their coefficients are actually total external heat
      transfer coefficients, not purely convective ones, as the calculation models
      assume. Data from the one human experiment that used heat flux sensors supports
      this conclusion and exposes the hazard of using a numerical model with several
      adjustable parameters that cannot be measured. Because the human-based equation
      is faulty, the values in the proposed charts are not correct. The equation that
      Ben Shabat et al. (Int J Biometeorol 56(4):639-51, 2013) propose to calculate
      WCET should not be used. 

PMID- 24924913
TI  - A new route to metal azides.
AB  - Beside several other applications, metal azides can be used for the synthesis of
      nitridophosphates and binary nitrides. Herein we present a novel synthetic access
      to azides: Several metals, such as main-group, transition metals, and rare-earth
      metals, react with silver azide in liquid ammonia as a solvent giving the
      corresponding metal azides. In this work Mn(N3)2, Sn(N3)2, and Eu(N3)2, as well
      as their ammonia complexes were synthesized for the first time through low
      temperature methods. Also a simpler access to Zn(N3)2 was possible. At room
      temperature and the respective vapor pressure of NH3, it became possible to grow
      single crystals of the dinuclear holmium azide [Ho2(MU
      NH2)3(NH3)10](N3)3?1.25NH3. We are confident that this new route could lead to
      novel metal azides as well as nitrides of the main-group, the transition, and the
      rare-earth metals upon careful decomposition.

PMID- 24924914
TI  - Ultrafast volumetric B1 (+) mapping for improved radiofrequency shimming in 3
      tesla body MRI.
AB  - PURPOSE: To evaluate the use of the recently proposed ultrafast B1 (+) mapping
      approach DREAM (Dual Refocusing Echo Acquisition Mode) for a refinement of
      patient adaptive radiofrequency (RF) shimming. MATERIALS AND METHODS: Volumetric
      DREAM B1 (+) calibration scans centered in the upper abdomen were acquired in 20
      patients and three volunteers with written informed consent at a clinical dual
      source 3 Tesla (T) MR system. Based on these data, RF transmit settings were
      optimized by central-slice based RF-shimming (CS-RF shim) and by a refined, multi
      slice adaptive approach (MS-RF shim). Simulations were performed to compare flip
      angle accuracy and B1 (+) homogeneity (cv = stddev/mean) achieved by CS-RF shim
      versus MS-RF shim for transversal and coronal slices, and for volume shimming on
      the spine. RESULTS: By MS-RF shim, mean deviation from nominal flip angle was
      reduced to less than 11% in all slices, all targets, and all subjects. Relative
      improvements in B1 (+) cv (MS-RF shim versus CS-RF) were up to 14%/39%/47% in
      transversal slices/coronal slices/ spine area. CONCLUSION: Volumetric information
      about B1 (+) can be used to further improve the accuracy and homogeneity of the
      B1 (+) field yielding higher diagnostic confidence, and will also be of value for
      various quantitative methods which are sensitive to flip angle imperfections.

PMID- 24924915
TI  - Milk oligosaccharides over time of lactation from different dog breeds.
AB  - The partnership of humans and dogs goes back to over 10'000 years, yet relatively
      little is known about a dog's first extra-uterine nutrition particularly when it
      comes to milk oligosaccharides. We set out to identify and quantify milk
      oligosaccharides over the course of lactation from different dog breeds (Labrador
      retriever, Schnauzer and 3 Alaskan husky crossbreeds). To this end, 2 different
      chromatographic methods with fluorescence and mass spectrometry detection were
      developed and one was validated for quantification. Besides lactose and lactose
      sulphate, we identified 2 different trisaccharides composed of 3 hexose units,
      3'sialyllactose (3'SL), 6'sialyllactose (6'SL), 2'fucosyllactose (2'FL), and a
      tetrasaccharide composed of 2 hexoses, an N-acetylhexosamine and a deoxyhexose.
      3'SL was present at the highest levels in milk of all dog breeds starting at
      around 7.5 g/L and dropping to about 1.5 g/L in the first 10 days of lactation.
      6'SL was about 10 times less abundant and 2'FL and the tetrasaccharide had rather
      varying levels in the milk of the different breeds with the tetrasaccharide only
      detectable in the Alaskan husky crossbreeds. The longitudinal and quantitative
      data of milk oligosaccharides from different dog breeds are an important basis to
      further our understanding on their specific biological roles and also on the
      specific nutritional requirements of lactating puppies. 

PMID- 24924917
TI  - Heart remodeling and ischemia-reperfusion arrhythmias linked to myocardial
      vitamin d receptors deficiency in obstructive nephropathy are reversed by
      paricalcitol.
AB  - Cardiovascular disease is often associated with chronic kidney disease and vice
      versa; myocardial vitamin D receptors (VDRs) are among the probable links between
      the 2 disorders. The vitamin D receptor activator paricalcitol protects against
      some renal and cardiovascular complications. However, the structural and
      electrophysiological effects of myocardial vitamin D receptor modification and
      its impact on the response to ischemia-reperfusion are currently unknown. This
      work attempted to determine whether obstructive nephropathy induced myocardial
      changes (in rats) linked to vitamin D receptor deficiency and to ventricular
      arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and
      Sham-operated rats were treated with either paricalcitol (30 ng/kg/d
      intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found
      that obstructed rats showed a reduction in VDRs and an increase in angiotensin II
      type 1 receptor expression (messenger RNA and protein), suffered fibrosis
      (determined by Masson trichrome stain) and myofibril reduction with an increase
      in mitochondrial size, and had dilated crests (determined by electron
      microscopy). These changes were reversed by paricalcitol. In 8 additional hearts
      per group, we found that obstructed rats showed a higher incidence of ventricular
      fibrillation during reperfusion (after 10 minutes of regional ischemia) than did
      those treated with paricalcitol. The action potential duration was prolonged
      throughout the experiment in paricalcitol-treated rats. We conclude that the
      reduction in myocardial vitamin D receptor expression in obstructed rats might be
      related to myocardial remodeling associated with an increase in arrhythmogenesis
      and that paricalcitol protects against these changes by restoring myocardial
      vitamin D receptor levels and prolonging action potentials. 

PMID- 24924916
TI  - Mitochondrial Hsp90s suppress calcium-mediated stress signals propagating from
      mitochondria to the ER in cancer cells.
AB  - BACKGROUND: Resistance to cell death in the presence of stressful stimuli is one
      of the hallmarks of cancer cells acquired during multistep tumorigenesis, and
      knowledge of the molecular mechanism of stress adaptation can be exploited to
      develop cancer-selective therapeutics. Mitochondria and the endoplasmic reticulum
      (ER) are physically interconnected organelles that can sense and exchange various
      stress signals. Although there have been many studies on stress propagation from
      the ER to mitochondria, reverse stress signals originating from mitochondria have
      not been well reported. METHODS: After inactivation of the proteins by
      pharmacologic and genetic methods, the signal pathways were analyzed by
      fluorescence microscopy, flow cytometry, MTT assay, and western blotting. A mouse
      xenograft model was used to examine synergistic anticancer activity and the
      action mechanism of drugs in vivo. RESULTS: We show in this study that
      mitochondrial heat shock protein 90 (Hsp90) suppresses mitochondria-initiated
      calcium-mediated stress signals propagating into the ER in cancer cells.
      Mitochondrial Hsp90 inhibition triggers the calcium signal by opening the
      mitochondrial permeability transition pore and, in turn, the ER ryanodine
      receptor, via calcium-induced calcium release. Subsequent depletion of ER calcium
      activates unfolded protein responses in the ER lumen, thereby increasing the
      expression of a pro-apoptotic transcription factor, CEBP homologous protein
      (CHOP). Combined treatment with the ER stressor thapsigargin and the
      mitochondrial Hsp90 inhibitor gamitrinib augmented interorganelle stress
      signaling by elevating CHOP expression, and showed synergistic cytotoxic activity
      exclusively in cancer cells in vitro and in vivo. CONCLUSIONS: Collectively,
      mitochondrial Hsp90s confer cell death resistance to cancer cells by suppressing
      the mitochondria-initiated calcium-mediated interorganelle stress response.

PMID- 24924918
TI  - Cancer-related identities in people diagnosed during late adolescence and young
      adulthood.
AB  - OBJECTIVES: Identity labels with which people diagnosed with cancer identify may
      have important implications for post-cancer adjustment, yet little is known about
      these identities, and virtually nothing about them in people diagnosed during
      late adolescence and young adulthood (LAYA). We examined (1) the extent to which
      LAYA participants endorse different identities, (2) relations between identities
      and subsequent adjustment (positive/negative impact of cancer, quality of life,
      health behaviours), and (3) coping as mediating identity-adjustment links.
      DESIGN: A longitudinal study in which 120 participants at Time 1 (T1) and 84
      participants at Time 2 (T2; 1 year later) were assessed. METHODS: Participants
      had been diagnosed between ages 15 and 39. Demographics, cancer-related
      variables, adjustment, and identities (victim/patient/someone who has had
      cancer/survivor/conqueror/member of the cancer community) were measured. RESULTS:
      Late adolescence and young adulthoods with cancer identify with a variety of
      terms. At both time points, someone who has had cancer was the most highly
      endorsed identity. Survivor and member of the cancer community were also
      frequently chosen. Generally, T1 survivor, conqueror, and member of the cancer
      community identities were positively correlated with T2 adjustment, whereas
      victim and patient identities were negatively correlated with T2 adjustment. Both
      T1 member of the cancer community identity and T2 emotional expression coping
      independently and positively predicted T2 positive self-evaluation even when T1
      positive self-evaluation was controlled. CONCLUSIONS: Forming empowering
      identities (e.g., survivor) and emphasizing community identity (member of the
      cancer community) appear helpful to post-cancer adjustment. Future studies need
      to examine cancer-related identities and mechanisms explaining identity
      adjustment links in this understudied group.

PMID- 24924920
TI  - The Kv1.3 potassium channel is localized to the cis-Golgi and Kv1.6 is localized
      to the endoplasmic reticulum in rat astrocytes.
AB  - The functions of voltage-gated potassium (Kv) channels in neurons have been well
      defined, whereas their roles in glial cells are not fully understood. Kv1.1,
      Kv1.3 and Kv1.6 are endogenously expressed in C6 astrocytoma cells, but their
      trafficking and subcellular localization have not been well studied. In C6 cells,
      Kv1.1 was localized to the cell surface, Kv1.3 was predominantly localized in the
      cis-Golgi, and Kv1.6 was enriched in the endoplasmic reticulum. Disruption of the
      Golgi stacks with brefeldin A treatment redirected Kv1.3 to the endoplasmic
      reticulum, further confirming that Kv1.3 was localized in the Golgi. Denaturing
      and reducing immunoblot analysis identified an expected Kv1.3 monomer and an
      unexpected Kv1.3 dimer/aggregate. These two forms had different protein half
      lives: that of the monomer form T1/2 was 5.1 h, whereas the dimer/aggregate form
      was stable over the 8-h measurement period. The Kv1.3 dimer/aggregate form on
      immunoblots appeared to be correlated with its Golgi retention, based on
      examination with several cell types that expressed Kv1.3. Glycosidase treatment
      showed that Kv1.3 contained complex-type N-glycans terminated with sialic acids,
      suggesting that Kv1.3 had traveled to the trans-Golgi network for sialylation
      before it was recycled to the cis-Golgi for retention. Inhibition of N
      glycosylation did not affect Kv1.3 localization, indicating that N-glycans did
      not play a role in its Golgi retention. Thus, Kv1.3 appears to be distributed to
      the cis-Golgi membrane of rat astrocytes in a similar way as a Golgi resident
      protein, and this unusual distribution appears to be correlated with its SDS/2
      mercaptoethanol-resistant dimer/aggregate forms on immunoblots.

PMID- 24924919
TI  - A natural experiment to examine the impact of park renewal on park-use and park
      based physical activity in a disadvantaged neighbourhood: the REVAMP study
      methods.
AB  - BACKGROUND: Modifying the built environment by improving parks is potentially a
      sustainable way to increase population level physical activity. Despite
      considerable investment in parks and park renovations, few natural experiments on
      the impact of improving amenities on park use and park-based physical activity
      have been conducted. REVAMP is a natural experiment that aims to examine whether
      park improvement increases overall park usage, park-based physical activity and
      active travel to and from the park in the intervention compared with the control
      park over a two-year period; and to identify which specific aspects of the park
      refurbishment attracts park visitors and encourages park users to be more active.
      This paper describes the methods of the REVAMP study. METHODS: The intervention
      park is a large regional park (329 hectares) located in a low socio-economic
      status (SES) area in the north-eastern suburbs of Melbourne, Australia. The
      control park is a regional park (120 hectares) located in a high SES area in the
      eastern suburbs of Melbourne. Multiple methodologies to evaluate the impact of
      the park renovation are being employed including: cross-sectional surveys of
      local residents living near the two parks, direct observations of park users,
      intercept surveys with park users, and electronic monitoring of path usage and
      car traffic within the parks. Baseline measures were conducted in April-May 2013
      (T1), and an innovative play space suitable for children of all ages and
      abilities was installed at the intervention park between September 2013 and
      February 2014. Follow-up measures will be repeated in April-May 2014 (T2) and
      April-May 2015 (T3). All methodologies will be completed at both the intervention
      and control parks at all three time-points, with the exception of the cross
      sectional survey of local residents which will only be conducted at T1 and T3.
      CONCLUSION: This research will inform future park developments, and will
      contribute to creating an evidence base of the impact of park refurbishment, and
      the development of natural experiment methodology. TRIAL REGISTRATION: Current
      controlled trial ISRCTN50745547, registration date 11.1.2014.

PMID- 24924921
TI  - Characterization and quantitative amino acids analysis of analgesic peptides in
      cinobufacini injection by size exclusion chromatography, matrix-assisted laser
      desorption/ionization time of flight mass spectrometry and gas chromatography
      mass spectrometry.
AB  - Cinobufacini injection that comes from the water extract of Bufo bufo gargarizans
      Cantor skin is widely used for cancer treatment in China. Peptide is one of its
      major types of constituents, however the biological effects and content of this
      injection are little reported. In present study, the analgesic effect of peptides
      was determined and evaluated by in-vivo models. To characterize and
      quantitatively analyze these peptides, a reliable and efficient method combining
      size exclusion chromatography and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry with amino acid analysis was developed. The
      peptides presented as a series of analogs with similar molecular weights mostly
      ranging from 2 to 8 kDa. The amino acid analysis by gas chromatography mass
      spectrometry (GC-MS) was developed to determine both free and combined amino
      acids (FAA and CAA) in cinobufacini injection. This method achieved good
      linearity (R(2) , 0.9909-0.9999) and low limit of detection and quantification.
      FAA and CAA samples were efficiently analyzed by modified Phenomenex EZ: faast
      procedure. For the sample analysis, the method showed good repeatability
      (relative standard deviation, RSD <= 10%). For most FAA and CAA the mean
      recoveries were >80% with RSD <10%. The GC-MS based method is useful for quality
      assurance of both FAA and CAA in cinobufacini injection.

PMID- 24924922
TI  - The high prevalence of serine protease autotransporters of Enterobacteriaceae
      (SPATEs) in Escherichia coli causing neonatal septicemia.
AB  - Serine protease autotransporters of Enterobacteriaceae (SPATEs) are secreted
      proteins demonstrating diverse virulence functions. The distribution of SPATEs is
      studied among diarrheagenic and extraintestinal pathogenic Escherichia coli.
      However, the contribution of SPATEs to the virulence of neonatal septicemic
      Escherichia coli (NSEC) has not yet been elucidated. This study was undertaken to
      evaluate the prevalence and phylogenetic distribution of different subtypes of
      SPATEs among NSEC. The presence of virulence factors and subtypes of SPATEs among
      different E. coli isolates was determined by polymerase chain reaction (PCR). E.
      coli phylogrouping was done by triplex PCR. Clonality of the isolates was
      assessed by pulsed-field gel electrophoresis (PFGE). The presence of SPATEs was
      significantly higher among the septicemic isolates (89 %) than the fecal (7.5 %)
      and environmental isolates (2.5 %). Vat (vacuolating autotransporter toxin) and
      Sat (secreted autotransporter toxin) were found to be the two most predominant
      SPATEs. The incidence of SPATEs was high in septicemic isolates of phylogroups A
      and B1 (87 %), lacking other virulence factors. The high prevalence of SPATEs in
      the non-B2 phylogroups of septicemic isolates in comparison with fecal and
      environmental isolates indicates an association of SPATEs with NSEC. The NSEC
      isolates were found to be clonally distinct, suggesting that the high prevalence
      of SPATEs was not due to clonal relatedness of the isolates. This study is the
      first to show the association of SPATEs with NSEC. The presence of SPATEs in the
      septicemic/NSEC isolates may be considered as the most discriminatory trait
      studied here.

PMID- 24924923
TI  - The relationship between IL-28B polymorphisms and the response to peginterferon
      alfa-2a monotherapy in anti-HBe-positive patients with chronic HBV infection.
AB  - The impact of interleukin 28B (IL-28B) on the results of interferon (IFN)-based
      therapy in patients chronically infected with hepatitis B virus (HBV) is poorly
      understood. The aim of this study was to evaluate the relationship between IL-28B
      markers and the response to IFN monotherapy in Polish patients with anti
      hepatitis B e (HBe)-positive chronic hepatitis B (CHB). We determined three
      single-nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, and
      rs8099917) in 86 patients who were treated with pegylated interferon (PEG-IFN)
      for 48 weeks. The effectiveness of the therapy was evaluated based on the
      virological and biochemical response. The primary efficacy parameters were the
      HBV DNA viral load below 400 IU/ml and 2,000 IU/ml in combination with alanine
      aminotransferase (ALT) normalization (<40 IU/l), measured 24 weeks after the
      treatment. Viral load below 400 IU/ml or 2,000 IU/ml with ALT normalization was
      achieved by 37 % and 46 % of patients, respectively. It has been shown that the
      distribution of IL-28B genotypes in the dominant genetic model in patients with
      different therapeutic success differ significantly only for rs12979860. The IL
      28B rs12979860 CC genotype was associated with lower treatment success [odds
      ratio (OR), 0.31; p = 0.025 and OR, 0.37; p = 0.044 for <400 IU/ml HBV DNA with
      <40 IU/l ALT, and <2,000 IU/ml HBV DNA with <40 IU/l ALT, respectively]. However,
      in the conditional logistic regression analysis adjusted by factors associated
      with combined response, rs12979860 was significantly associated only with <400
      IU/ml HBV DNA with <40 IU/l ALT (OR, 0.24; p = 0.026). IL-28B polymorphisms have
      prognostic significance in assessing the treatment effectiveness based on the
      virological and biochemical response of patients with anti-HBe-positive CHB.

PMID- 24924924
TI  - Genetic variants in PVRL2-TOMM40-APOE region are associated with human longevity
      in a Han Chinese population.
AB  - PURPOSE: Human longevity results from a number of factors, including genetic
      background, favorable environmental, social factors and chance. In this study, we
      aimed to elucidate the association of human longevity with genetic variations in
      several major candidate genes in a Han Chinese population. METHODS: A case
      control association study of 1015 long-lived individuals (aged 90 years or older)
      and 1725 younger controls (30-70 years old) was undertaken. Rs2075650 in TOMM40
      was firstly genotyped using the ABI SNaPshot method in an initial cohort
      consisted of 597 unrelated long-lived individuals and 1275 younger controls
      enrolled from Sichuan. Secondly, eighteen tag single-nucleotide polymorphisms
      (SNPs) in the PVRL2-TOMM40-APOE locus were genotyped for extensive study in the
      same cohort. Finally, 5 associated SNPs were genotyped in a replication cohort
      including 418 older individuals and 450 younger controls. The genotype and allele
      frequencies were evaluated using the chi2 tests. The linkage disequilibrium (LD)
      block structure was examined using the program Haploview. RESULTS: The case
      control study of rs2075650 in TOMM40 showed significant difference in allele
      frequencies between cases and controls (P = 0.006) in an initial study. Of the 18
      SNPs genotyped, rs405509 in APOE and another three SNPs (rs12978931, rs519825 and
      rs395908) in the PVRL2 gene also showed significant association with human
      longevity in extensive study in the same cohort. Rs2075650 in TOMM40, rs405509 in
      APOE and rs519825 in PVRL2 showed a significant association with human longevity
      in a replication cohort. CONCLUSION: These results suggested that PVRL2, TOMM40
      and APOE might be associated with human longevity. However, further research is
      needed to identify the causal variants and determine which of these genes are
      involved in the progress of human longevity.

PMID- 24924925
TI  - Properties of the plant- and manure-derived biochars and their sorption of
      dibutyl phthalate and phenanthrene.
AB  - The properties of plant residue-derived biochars (PLABs) and animal waste-derived
      biochars (ANIBs) obtained at low and high heating treatment temperatures (300 and
      450 degrees C) as well as their sorption of dibutyl phthalate (DBP) and
      phenanthrene (PHE) were investigated in this study. The higher C content of PLABs
      could explain that CO2-surface area (CO2-SA) of PLABs was remarkably high
      relative to ANIBs. OC and aromatic C were two key factors influencing the CO2-SA
      of the biochars. Much higher surface C content of the ANIBs than bulk C likely
      explained that the ANIBs exhibited higher sorption of DBP and PHE compared to the
      PLABs. H-bonding should govern the adsorption of DBP by most of the tested
      biochars and pi-pi interaction play an important role in the adsorption of PHE by
      biochars. High CO2-SA (>200 m(2) g(-1)) demonstrated that abundant nanopores of
      OC existed within the biochars obtained 450 degrees C (HTBs), which likely result
      in high and nonlinear sorption of PHE by HTBs.

PMID- 24924927
TI  - Scalable low-cost SnS(2) nanosheets as counter electrode building blocks for dye
      sensitized solar cells.
AB  - A new type of semitransparent SnS2 nanosheet (NS) films were synthesized using a
      simple and environmentally friendly solution-processed approach, which were
      subsequently used as a counter electrode (CE) alternative to the noble metal Pt
      for triiodide reduction in dye-sensitized solar cells (DSSCs). The resultant SnS2
      -based CE with a thickness of about 300 nm exhibited excellent electrochemical
      catalytic activity for catalyzing the reduction of triiodide and demonstrated
      comparable power conversion efficiency of 7.64 % with that of expensive Pt-based
      CE in DSSCs (7.71 %). When functionalized with a small amount of carbon
      nanoparticles, the SnS2 NS-based CE showed even better performance of 8.06 % than
      Pt under the same conditions. Considering the facile fabrication method, optical
      transparency, low cost, and remarkable catalytic property, this study on SnS2 NSs
      may shed light on the large-scale production of electrocatalytic electrode
      materials for low-cost photovoltaic devices. 

PMID- 24924928
TI  - Factor analysis of open-field behavior in the rat (Rattus norvegicus):
      application of the three-way PARAFAC model to a longitudinal data set.
AB  - We examined the multivariate nature of open-field behavior in adult male rats (n
      = 26) by subjecting a longitudinal data set, obtained during 4 open-field test
      sessions (4 min in duration and spaced 48 h apart), to a three-way PARAFAC
      analysis. Unlike conventional two-way factor analytical models, the PARAFAC
      procedure allows for the direct factor analysis of 3-dimensional arrays, which
      then provided a unique factor solution to the longitudinal data set. The PARAFAC
      analysis extracted 2 factors: i) emotional reactivity and ii) exploratory
      behavior. These two factors changed in temporal prominence, with animals showing
      greater emotional reactivity on the first test session, and greater levels of
      exploration on the third and fourth test sessions. These results are in general
      agreement with previous findings which used more conventional factor analytic
      approaches. These findings indicate that multivariate procedures, such as the
      PARAFAC analysis, can be helpful in the quantitative characterization of
      behavioral phenomena in a more 'realistic' manner. 

PMID- 24924926
TI  - Prospects for novel inhibitors of peptidoglycan transglycosylases.
AB  - The lack of novel antimicrobial drugs under development coupled with the
      increasing occurrence of resistance to existing antibiotics by community and
      hospital acquired infections is of grave concern. The targeting of biosynthesis
      of the peptidoglycan component of the bacterial cell wall has proven to be
      clinically valuable but relatively little therapeutic development has been
      directed towards the transglycosylase step of this process. Advances towards the
      isolation of new antimicrobials that target transglycosylase activity will rely
      on the development of the enzymological tools required to identify and
      characterise novel inhibitors of these enzymes. Therefore, in this article, we
      review the assay methods developed for transglycosylases and review recent novel
      chemical inhibitors discovered in relation to both the lipidic substrates and
      natural product inhibitors of the transglycosylase step. 

PMID- 24924929
TI  - Patch choice by guinea pigs: is patch recognition important?
AB  - Using four Guinea pigs (Cavia aperea f. porcellus) as subjects we tested the
      predictions of three versions of a rate-maximizing model in a patch choice
      foraging task. Patches were of two types which differed in interval between
      captures and in number of prey within each patch. In the model, the optimal
      policy is expressed as the threshold difference in inter-prey interval between
      the two patch types beyond which it pays to reject poor patches. The model
      versions are: a) recognizer (capable of identifying patch type on encounter and
      patch exhaustion upon capturing the last prey); b) timer (must wait a time r
      before identifying a patch as being poor, but can identify patch exhaustion at
      the last capture); and c) dual timer (as timer but needs an additional waiting
      time to detect patch exhaustion). In the experiment we used patches containing
      only one prey item. The results showed that patches were accepted in close
      agreement with the predictions of the timer and dual-timer models, but only the
      assumptions of the second model were met, as guinea pigs took considerable time
      to identify poor patches and also some time to abandon exhausted patches. These
      results showed that although cues for patch type were present, the guinea pigs
      did not behave as recognizers. We discuss and advocate the use of realistically
      constrained optimal foraging models. 

PMID- 24924930
TI  - Proceptive and receptive aspects of oestrus behaviour in gilts.
AB  - Proceptive and receptive aspects of behaviour were studied during the oestrus
      cycle of the female pig. These aspects were studied in a T-maze with one or two
      stimulus compartments that did or did not contain a teaser boar. Receptive
      behaviour was observed during several consecutive days and was quantified in
      front of the boar by using the back pressure test (BPT). Three aspects of
      proceptive behaviour, i.e. the tendency to 'search the boar', 'stay close to the
      boar' and 'to present' in front of the boar peaked in the middle of the receptive
      period, and in most gilts on the day preceding the last receptive day (Experiment
      1). In contrast, preference for a particular boar, another aspects of proceptive
      behaviour, was only expressed during the days preceding and following the
      receptive period (Experiment 2). The results are discussed in terms of the
      possible functional implications of proceptive and receptive behaviour in
      relation to fertilization. 

PMID- 24924931
TI  - Hoarding behavior in the pigeon (Columbia livia): performance under the
      restriction of food availability.
AB  - The effect of restriction of food availability on food-earning behavior was
      investigated in two pigeons (Columbia livia) in a closed economy paradigm.
      Experimental chambers that allowed them to store food were devised. They were
      exposed to two kinds of feeding conditions. One condition was a free-feeding
      condition in which the bird could earn food at any time of the day by pecking a
      key. The other was a restricted-feeding condition where the food availability was
      restricted only for a given time of day. Consequently, one bird overtly hoarded
      food. After the bird was exposed to the restricted-feeding condition, this bird
      learned to obtain extra food and left some food uneaten for later consumption.
      Moreover, this bird utilized the hoarded food and compensated for the reduction
      of the income. Thus, after an experience with the restriction of food
      availability, the bird learned to obtain extra food that was not consumed
      immediately and left it uneaten.However, in the condition where essential food
      but not extra food could be earned, the bird did not hoard food. 

PMID- 24924932
TI  - Persistent neophobic behaviour in monkeys: A habit or a trait?
AB  - Studies on the effects of rearing conditions on behavioural development showed
      that most monkeys reared with surrogate mothers persistently avoided a big novel
      object (paper bag) whereas most monkeys reared by natural mothers would approach
      it. Conditioned fear and conditioned avoidance, observational learning, and lack
      of support by the mothers' presence could be excluded as possible causes; we
      established that the high incidence of phobic behaviour in surrogate-reared
      groups was caused by deprivation of maternal care. Results of further studies
      showed that the avoidance was not restricted to the object the Ss had been
      exposed to in infancy; monkeys still avoiding the bag at 2 years also avoided
      other big novel objects. Some researchers have found differences in the
      neurobiological status between surrogate-reared monkeys and mother-reared
      monkeys. However, the results of our experiments showed that both types of
      rearing condition produced avoiders as well as non-avoiders. The question under
      discussion here is whether avoidance of novelty is a habit or a trait. The
      relative importance of features of surrogates versus real mothers,
      characteristics of infants and differences in mothering style is discussed. 

PMID- 24924933
TI  - Some functional characteristics of avoidance of timeout from response-dependent
      food presentation in rats.
AB  - Three male and three female rats were first trained to respond on a Random
      Interval 15-s schedule on one (food) lever in a rodent operant conditioning
      chamber. They were then exposed to a condition in which food could only be
      obtained during a timein period which lasted 10 s or longer dependent upon
      whether or not subjects pressed another (avoidance) fever. If subjects did not
      press the other level during the 10-s timein, a 50-s timeout was presented during
      which food could not be obtained. Subjects first had the opportunity to avoid
      timeout presentation by pressing the avoidance level during timein or to escape
      the timeout by pressing the lever during timeout. A changeover delay of 2-s
      prevented food presentation immediately following avoidance lever-food lever
      sequences. All subjects pressed the avoidance lever to avoid or escape timeout,
      but only one of the subjects consistently pressed the avoidance lever when escape
      was no longer available. One more subject acquired consistent avoidance
      responding after reexposure to the avoidance/escape and avoidance only
      conditions. The four remaining subjects were then exposed to a signalled
      avoidance procedure in which a 5-s stimulus change preceded timeout presentation.
      Three of the subjects came to respond reliably on the avoidance lever when
      switched back to the unsignalled avoidance procedure. One of the subjects never
      acquired consistent avoidance responding. Functional control by the avoidance
      contingency was demonstrated during the final two experimental conditions in
      which the contingencies associated with the avoidance lever were systematically
      removed and reintroduced. 

PMID- 24924934
TI  - The effect of time between sessions on within-session patterns of responding.
AB  - Four pigeons pecked keys for food reinforcers delivered by variable interval 1
      min schedules during two successive 50-min sessions or one 100-min session. When
      50-min sessions were conducted, they were separated by a 0-, 10- or 30-min delay,
      spent either inside or outside of the experimental enclosure. Responding usually
      increased to a peak and then decreased within sessions. This pattern was not
      altered by either the length of the delay between sessions or by the place where
      the subjects spent the delay. These results suggest that the beginning of the
      session or the passage of a short time between sessions restores the conditions
      necessary to produce within-session changes in responding. The results are
      incompatible with theories that explain these changes in terms of recovery from
      the handling routine, accumulation of arousal, priming, fatigue, or satiation.
      They can be reconciled with theories that attribute within-session changes in
      responding to reinstatement of memory or changes in attention only by arguing
      that memory and attentional adjustments are erased quickly between sessions. 

PMID- 24924935
TI  - The development of responses to novel-coloured objects in male and female
      domestic chicks.
AB  - Male and female domestic chicks were trained to peck on a small coloured (red or
      green) box for food reinforcement. They were then presented with one box
      identical to that used during training (familiar) and one of a different colour
      (unfamiliar) and their preferences were assessed in a simultaneous free choice
      test. The novel colour was green in chicks trained with a red box and red in
      chicks trained with a green box. Chicks showed marked variations in their
      preferences for familiarity and novelty as a function of age and sex. In chicks
      trained with a green box preferences for the familiar colour were stronger in
      females than in males at all ages of test. A similar sex difference was observed
      in chicks trained with a red box, except that at around day 9, when males showed
      temporarily stronger preferences for familiarity than females. When comparing
      males and females of red-trained chicks to those of green-trained chicks, a shift
      in colour prefernce, from red to green, was apparent from day 9 in both sexes,
      though temporarily stronger in females than in males. Levels of preference for
      the familiar object showed a peak (centred at around day 5/6) and two dips
      (centred at around day 4/5 and day 10/11) in both sexes irrespective of colour.
      Results are discussed in relation to current evidence for simultaneous changes in
      the brain and in the behaviour of young chicks during development. 

PMID- 24924936
TI  - The effect of separate reinforced and nonreinforced exposures to a context
      participating in a Pavlovian discrimination procedure.
AB  - Rats were subjected to a Pavlovian discrimination procedure in which a target
      stimulus was followed by food in Context X and followed by nothing in a
      distinctively different Context Y. Two experiments sought to determine the effect
      of postacquisition manipulations regarding Context Y, on responding to the target
      in that context. In Experiment 1A, the effect of separate nonreinforced exposures
      to Context Y was examined and in Experiment 1B, the effect of a separate
      reinforced exposure was assessed in four groups of rats receiving different
      amounts of deliveries of the reinforcer in Context Y. It was found that both
      nonreinforced and reinforced exposures to Context Y had an adverse effect on the
      attenuation of responding to the target that was originally observed in that
      context at the end of discrimination training. The results were discussed in view
      of an occasion-setting account and of more traditional models of associative
      learning. 

PMID- 24924937
TI  - Endogenous rectilinear guidance in fish: Is it adjusted by reference to the sun?
AB  - Previous works have shown that small migratory fish, when placed in an annular
      channel with central symmetrical lighting, swim continuously in one direction.
      This has been interpreted as a sunlight orientation response which assists in
      straight-line migration. The purpose of the present work is to test whether these
      fish have an endogenous rectilinear mechanism (inertial guidance) and if this
      mechanism is in some way associated with the sun directional orientation
      response. A group of small schooling fish, Cheirodon pulcher, was placed in an
      annular channel with central symmetrical lighting. Fish swam steadily in a
      clockwise direction during two weeks. They were then placed individually in a
      diffuse-light arena for 90 min and their movements were video-recorded. The
      number of right and left turns was counted. Fish rotated in the same direction as
      in the annular channel. In contrast, fish from a holding tank made equal numbers
      of right and left turns. The maintenance of turning behaviour after removal of
      the turning-promotive conditions suggests that an endogenous rectilinear guidance
      mechanism was modified while fish were swimming at a constant angle to light in
      the annular channel. This mechanism would be normally adjusted by reference to
      the sun. 

PMID- 24924938
TI  - Social and non-social open field behaviour of rats under light and noise
      stimulation.
AB  - In two experiments, male rats were observed in pairs under different
      environmental stimulations in an open field. In Experiment 1, white noise of 85
      dB(A) reduced social activities and increased defecation compared to 75 dB(A) and
      65 dB(A). In Experiment 2, the illumination of the open field was varied in
      addition to a variation of the noise intensity. Again, 85 dB(A) as compared to 50
      dB(A) reduced social activities and increased defecation, but also led to changes
      in non-social behaviours such as sniffing, grooming, and rearing. In contrast,
      400 lx did not differ substantially in its effects from 40 lx in any of the
      observed behavioural categories. Altogether, the behaviour pattern under 85 dB(A)
      white noise cannot satisfactorily be explained only by increased anxiety of fear.
      Alternative explanations are discussed. 

PMID- 24924939
TI  - Description du comportement sexuel de Calliphora vomitoria (Diptera:
      Calliphoridae) par une technique d'analyse de textes.
AB  - Description of the sexual behaviour of Calliphora vomitoria (Diptera:
      Calliphoridae) with a lexical analysis software package. The sexual behaviour of
      Calliphora vomitoria was described using a lexical analysis software package
      considering courtship as a series of words, without any arbitrary categorization.
      Normal as well as manipulated partners of both sexes were presented to the males.
      Results showed that normal courtship and copulation occurred when the wings were
      modified but present and correctly oriented, whereas perturbations were observed
      and copulation disappeared after inversion and various head modifications.
      Missing elements (head and wings) were less disruptive than their inversion. If
      the partner was supposed to be scanned from the head to the abdomen via the wings
      and if it was supposed to perceive the relative position of these different
      parts, it is obvious that the absence of an element did not act as an error
      message and courtship and copulation were preserved. On the other hand, inversion
      of the same elements seemed to induce wrong or inconsistent informations
      affecting courtship structure, probably because of sequence disturbance. The
      courtship preservation in front of every kind of manipulation leads us to
      question what image of the sexual partner is constructed. 

PMID- 24924940
TI  - How should parents respond to a reduction in litter size: Abandonment or extra
      care?
AB  - Although natural selection may favour the evolution of an optimal brood size,
      unpredictable environmental factors can intervene to render the brood either
      considerably larger or smaller than this optimum. The question therefore arises
      as to how parents should respond to unusually large or small litters. Solutions
      to this problem which involve abandonment of the offspring or brood reduction,
      for example by infanticide, have received most theoretical and empirical
      attention. For small mammalian litters, however, evidence that parents employ
      these behavioural strategies is sparse. I suggest that, under certain conditions,
      an alternative to abandonment and infanticide of small litters in mammals is an
      increase in total parental care above that seen in larger litters. Evidence is
      presented which supports this possibility. This strategy may allow parents to
      compensate for the loss of offspring by producing a small number of high quality
      individuals. It is most likely to occur when opportunities for rapid rebreeding
      are limited, and when increases in parental care have strong effects on offspring
      quality. Interest in abandonment and infanticide has diverted attention away from
      this alternative parental response to small litters. Studies of this response are
      encourage, not least because they will focus attention on the poorly understood
      relationship between parental care and offspring quality. 

PMID- 24924941
TI  - Specific differences in sound production and pattern recognition in tettigoniids.
AB  - A brief comparative description of the stridulatory songs of nine different
      tettigoniid species is given to introduce a set of four parameters (phase of
      sound production during opening and closing movement of the wings, syllable
      repetition mode, syllable similarity, and impulse pattern of the syllables) to
      characterize the temporal pattern of tettigoniid songs. The importance of
      different song parameters for female phonotaxis was investigated in two
      tettigoniid species (Ephippiger ephippiger and Tettigonia viridissima). Two
      choice experiments revealed that the impulse pattern of the closing syllable is
      an important parameter for the phonotactic behaviour of E. ephippiger, whereas
      the syllable pattern is a decisive parameter for species discrimination in T.
      viridissima. 

PMID- 24924942
TI  - Investigations of the nature of lambs' individual odour signatures.
AB  - In an attempt to gain further insight into the sources and characteristics of
      lambs' olfactory signatures, we observed ewes' responses to familiar and alien
      young whose odours were experimentally manipulated. When tested several hours
      after parturition, ewes accepted their own lambs that had been anointed with an
      artificial odorant at birth, but rejected alien lambs bearing either that same
      familiar scent or a novel odour. Ewes nonetheless appeared capable of
      discriminating between alien lambs treated with the familiar versus novel
      odorants. Alien young anointed with amniotic fluid collected from the ewes' own
      offspring were rejected to the same extent as aliens treated with their own
      (alien) amniotic fluid. Thus, neither artificial odorants nor amniotic fluid
      masked the lambs' individual odours, nor did they preclude ewes' learning of
      those phenotypic traits. Ewes may be predisposed to learn a limited range of
      biological odours associated with their newborn lamb, and such individually
      recognizable cues appear not to be carried in the amniotic fluid nor acquired
      postnatally from the mother. 

PMID- 24924943
TI  - Site fidelity in foraging wood-ants Formica aquilonia yarrow and its influence on
      the distribution of foragers in a regenerating environment.
AB  - The proportions of the population of red wood-ants Formica aquilonia Yarrow,
      foraging for sucrose at two artificial feeding sites in the laboratory,
      approximated to those predicted by the ideal free distribution (Lamb and Ollason,
      1993). It was assumed that, for the foraging population to attain the ideal free
      distribution, each individual would visit and assess the availability of food at
      both feeding sites and distribute its foraging effort in proportion to the rate
      of regeneration of food. In order to demonstrate this, large samples of foragers
      at each of the feeding sites were colour-marked according to site. It was
      expected that the marked sample of foragers would in time become distributed as
      predicted by the ideal free distribution; instead, the distribution of marked
      ants was biased toward the site where they had been marked. Hence some
      individuals are not continually visiting and feeding at both patches, and such
      individuals will not be able directly to assess their feeding rates at each
      patch. There is, in principle, no way that such individuals can distribute
      themselves as predicted by the ideal free distribution, and as the site-faithful
      ants form a large proportion of the population, it appears that there is no way
      that the members of such a population can become so distributed. One resolution
      of this apparent paradox is provided by the behaviour of the mobile ants, the
      existence of which is demonstrated by observations of marked ants foraging at the
      site other than that at which they were marked. If the mobile members of the
      population assess the quality of both patches and distribute themselves to
      maximise their rates of feeding, the whole population will become distributed as
      predicted by the ideal free distribution. A modification of Ollason's (1987)
      model shows how this distribution could develop. It emerges that there is a
      minimum proportion of mobile ants in a population, below which the ideal free
      distribution will not develop, and that the distribution of foragers will depart
      from the ideal free distribution increasingly as the discrepancy between the
      regeneration rates of the patches of food increases. 

PMID- 24924944
TI  - Schedule-induced timeout: Effects of timeout-contingent delayed reinforcement.
AB  - Rats' lever pressing turned off stimuli associated with various response
      independent fixed-time schedules of food delivery and produced a timeout period
      during which food delivery could not occur. A lever press during timeout turned
      on the schedule-associated stimuli and reinstated the fixed-time schedule. Every
      response that produced timeout ended the timing of fixed time intervals; timeout
      terminating responses started the timing of fixed-time schedules over again. The
      percentage of session time spent in timeout periods generally increased as the
      rate of food delivery decreased. When food delivery could not occur, about half
      of the session time was spent in the stimulus condition formerly associated with
      timeout. The majority of timeout periods were initiated after 15 seconds or more
      had lapsed since the last food delivery. When timeout periods could not be
      produced, lever pressing rates either decreased or were not affected. The rate of
      food delivery appeared to be a primary determinant of time spent in timeout
      periods. The results may be inconsistent with interpretations emphasizing escape
      from aversive aspects of schedules of positive reinforcement. 

PMID- 24924945
TI  - Neuronal uptake of nanoformulated superoxide dismutase and attenuation of
      angiotensin II-dependent hypertension after central administration.
AB  - Excessive production of superoxide (O2(-)) in the central nervous system has been
      widely implicated in the pathogenesis of cardiovascular diseases, including
      chronic heart failure and hypertension. In an attempt to overcome the failed
      therapeutic impact of currently available antioxidants in cardiovascular disease,
      we developed a nanomedicine-based delivery system for the O2(-)-scavenging enzyme
      copper/zinc superoxide dismutase (CuZnSOD), in which CuZnSOD protein is
      electrostatically bound to a poly-l-lysine (PLL50)-polyethylene glycol (PEG)
      block copolymer to form a CuZnSOD nanozyme. Various formulations of CuZnSOD
      nanozyme are covalently stabilized by either reducible or nonreducible
      crosslinked bonds between the PLL50-PEG polymers. Herein, we tested the
      hypothesis that PLL50-PEG CuZnSOD nanozyme delivers active CuZnSOD protein to
      neurons and decreases blood pressure in a mouse model of angiotensin II (AngII)
      dependent hypertension. As determined by electron paramagnetic resonance
      spectroscopy, nanozymes retain full SOD enzymatic activity compared to native
      CuZnSOD protein. Nonreducible CuZnSOD nanozyme delivers active CuZnSOD protein to
      central neurons in culture (CATH.a neurons) without inducing significant neuronal
      toxicity. Furthermore, in vivo studies conducted in adult male C57BL/6 mice
      demonstrate that hypertension established by chronic subcutaneous infusion of
      AngII is significantly attenuated for up to 7 days after a single
      intracerebroventricular injection of nonreducible nanozyme. These data indicate
      the efficacy of nonreducible PLL50-PEG CuZnSOD nanozyme in counteracting
      excessive O2(-) and decreasing blood pressure in AngII-dependent hypertensive
      mice after central administration. Additionally, this study supports the further
      development of PLL50-PEG CuZnSOD nanozyme as an antioxidant-based therapeutic
      option for hypertension. 

PMID- 24924947
TI  - Outcomes in locally advanced rectal cancer with highly selective preoperative
      chemoradiotherapy.
AB  - BACKGROUND: This study compared outcomes after surgery alone for stage II/ III
      rectal cancer in a tertiary cancer unit versus highly selective use of
      preoperative chemoradiotherapy (CRT). METHODS: This was a single-centre
      retrospective cohort study of consecutive patients receiving potentially curative
      surgery for stage II and III primary rectal cancer. CRT was given only for
      magnetic resonance imaging-predicted circumferential resection margin (CRM)
      involvement and nodal disease (at least N2). Primary endpoints were CRM
      involvement and local recurrence rates. Secondary endpoints were systemic
      recurrence and overall survival. Data were analysed by log rank test, and
      univariable and multivariable analysis. RESULTS: Between 2002 and 2012, 363
      patients were treated for rectal cancer. After applying exclusion criteria, 266
      patients with stage II/III mid or low rectal cancer were analysed. Of these, 103
      received neoadjuvant CRT and 163 proceeded directly to surgery, seven of whom
      required postoperative radiotherapy; the latter patients were included in the
      neoadjuvant CRT group for analysis. There was a significant difference in local
      recurrence between the CRT and surgery-alone groups (6.5 versus 0 per cent at 5
      years; P = 0.040), but not in CRM involvement (7.2 versus 5.1 per cent; P =
      0.470), 5-year systemic recurrence (37.2 versus 43.0 per cent; P = 0.560) and
      overall survival (64.2 versus 64.6 per cent; P = 0.628) rates. Metastatic disease
      developed more frequently in low rectal cancers (odds ratio 0.14; P < 0.001),
      regardless of whether neoadjuvant treatment was delivered. CONCLUSION: Locally
      advanced rectal cancer does not necessarily require neoadjuvant CRT.

PMID- 24924946
TI  - Oxidative stress-mediated aldehyde adduction of GRP78 in a mouse model of
      alcoholic liver disease: functional independence of ATPase activity and chaperone
      function.
AB  - Pathogenesis in alcoholic liver disease (ALD) is complicated and multifactorial
      but clearly involves oxidative stress and inflammation. Currently, conflicting
      reports exist regarding the role of endoplasmic reticulum (ER) stress in the
      etiology of ALD. The glucose-regulated protein 78 (GRP78) is the ER homolog of
      HSP70 and plays a critical role in the cellular response to ER stress by serving
      as a chaperone assisting protein folding and by regulating the signaling of the
      unfolded protein response (UPR). Comprising three functional domains, an ATPase,
      a peptide-binding, and a lid domain, GRP78 folds nascent polypeptides via the
      substrate-binding domain. Earlier work has indicated that the ATPase function of
      GRP78 is intrinsically linked and essential to its chaperone activity. Previous
      work in our laboratory has indicated that GRP78 and the UPR are not induced in a
      mouse model of ALD but that GRP78 is adducted by the lipid electrophiles 4
      hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) in vivo. As impairment of GRP78
      has the potential to contribute to pathogenesis in ALD, we investigated the
      functional consequences of aldehyde adduction on GRP78 function. Identification
      of 4-HNE and 4-ONE target residues in purified human GRP78 revealed a marked
      propensity for Lys and His adduction within the ATPase domain and a relative
      paucity of adduct formation within the peptide-binding domain. Consistent with
      these findings, we observed a concomitant dose-dependent decrease in ATP-binding
      and ATPase activity without any discernible impairment of chaperone function.
      Collectively, our data indicate that ATPase activity is not essential for GRP78
      mediated chaperone activity and is consistent with the hypothesis that ER stress
      does not play a primary initiating role in the early stages of ALD. 

PMID- 24924948
TI  - MUC5B promoter polymorphisms and risk of coal workers' pneumoconiosis in a
      Chinese population.
AB  - Coal workers' pneumoconiosis (CWP) is characterized by fibrosing nodular lesions
      that eventually develop into progressive pulmonary fibrosis. Genetic variations
      have been recognized to be involved in the multi-factorial susceptibility to CWP,
      and MUC5B is a candidate lung fibrosis susceptibility gene. In the present study,
      we investigated possible genetic associations between three single nucleotide
      polymorphisms in MUC5B promoter region and CWP in a case-control study including
      686 CWP patients and 680 controls. Genotyping was carried out by TaqMan method.
      Only rs2672794 allele and genotype frequencies distributions were significantly
      different between CWP patients and controls (P = 0.017 and 0.046 for allele and
      genotype, respectively). The MUC5B rs2672794 CC genotype was associated with a
      significantly increased risk of CWP, compared with the TT genotype. Moreover,
      individuals with TC/CC genotype had an obviously increased risk of CWP than those
      with TT genotype, particularly among subgroups of dust exposure <27 years and
      smokers. This is the first report showing an association between the MUC5B
      rs2672794 polymorphism and CWP, and our results suggest that MUC5B rs2672794 CC
      genotype could increase the risk of CWP. Further studies are warranted to confirm
      our findings.

PMID- 24924949
TI  - Inhibition of human cytochrome P450 2E1 and 2A6 by aldehydes: structure and
      activity relationships.
AB  - The purpose of this study was to probe active site structure and dynamics of
      human cytochrome P4502E1 and P4502A6 using a series of related short chain fatty
      aldehydes. Binding efficiency of the aldehydes was monitored via their ability to
      inhibit the binding and activation of the probe substrates p-nitrophenol (2E1)
      and coumarin (2A6). Oxidation of the aldehydes was observed in reactions with
      individually expressed 2E1, but not 2A6, suggesting alternate binding modes. For
      saturated aldehydes the optimum chain length for inhibition of 2E1 was 9 carbons
      (KI=7.8 +/- 0.3 MUM), whereas for 2A6 heptanal was most potent (KI=15.8 +/- 1.1
      MUM). A double bond in the 2-position of the aldehyde significantly decreased the
      observed KI relative to the corresponding saturated compound in most cases. A
      clear difference in the effect of the double bond was observed between the two
      isoforms. With 2E1, the double bond appeared to remove steric constraints on
      aldehyde binding with KI values for the 5-12 carbon compounds ranging between 2.6
      +/- 0.1 MUM and 12.8 +/- 0.5 MUM, whereas steric effects remained the dominant
      factor in the binding of the unsaturated aldehydes to 2A6 (observed KI values
      between 7.0 +/- 0.5 MUM and >1000 MUM). The aldehyde function was essential for
      effective inhibition, as the corresponding carboxylic acids had very little
      effect on enzyme activity over the same range of concentrations, and branching at
      the 3-position of the aldehydes increased the corresponding KI value in all cases
      examined. The results suggest that a conjugated pi-system may be a key structural
      determinant in the binding of these compounds to both enzymes, and may also be an
      important feature for the expansion of the active site volume in 2E1.

PMID- 24924950
TI  - Nitrative modifications of alpha-enolase in hepatic proteins from diabetic rats:
      the involvement of myeloperoxidase.
AB  - Many studies reported that oxidative and nitrative stress might be important in
      the pathogenesis of diabetes and the development of its complications. In this
      study, we showed that alpha-enolase (EC 4.2.1.11, 2-phospho-d-glycerate
      hydrolase) was identified as the important target for oxidative and nitrative
      modifications in diabetic hepatic proteins. After 6 weeks of streptozotocin
      administration, alpha-enolase expression and nitration were clearly increased in
      diabetic rat liver, whereas the enolase activity and oxidation status were not
      significantly changed in diabetic group. By means of immunoprecipitation and
      liquid chromatography-tandem mass spectrometry analysis, it was found that Tyr 12
      and Tyr 257 of alpha-enolase were the most susceptible to nitration in diabetic
      rat liver. Moreover, myeloperoxidase (MPO) as a likely alternative mechanism for
      nitrative modification of alpha-enolase in vivo was apparently facilitated by the
      presence of higher MPO level and activity in diabetic liver, and fact that Tyr 12
      and Tyr 191 of enolase was nitrated by MPO/nitrite/H2O2 system in vitro. Further
      studies in vitro indicated that carbonyl formation, rather than tyrosine
      nitration, might make a major contribution to the inactivation of enolase. The
      present results provided the new evidence for alpha-enolase as a susceptive
      target for MPO-catalyzed nitrative modification in diabetes. They also suggested
      a potential contribution of nitrative and oxidative modifications of enolase to
      an impaired glycolytic activity in diabetic hepatic injury.

PMID- 24924951
TI  - Hollow nanospheres constructed by CoS2 nanosheets with a nitrogen-doped-carbon
      coating for energy-storage and photocatalysis.
AB  - Hierarchical CoS2 hollow nanospheres (HSs) with a nitrogen-doped-carbon coating
      (NC@CoS2 ) are fabricated by a simple solution method. The uniform 300 nm-sized
      NC@CoS2 HSs are composed of ultrathin nanosheet subunits with a thickness of
      around 2 nm. It was found that polyvinylpyrrolidone and ethylenediamine not only
      controlled the morphology of the products, but also provided the sources of
      nitrogen-doped carbon. Benefiting from their unique structural characteristics,
      hierarchical NC@CoS2 HSs can be applied in lithium-ion batteries,
      supercapacitors, and photocatalysis. When evaluated as an electrode material,
      NC@CoS2 with a coating of optimal thickness showed a high lithium-storage
      capability with a good cycling stability. Moreover, NC@CoS2 had a remarkable
      supercapacitive performance and photocatalytic activity. The attractive
      electrochemical and photocatalytic performances were attributed to the overall
      structural features of the NC@CoS2 hollow spheres: the N-doped-carbon (NC)
      coating, hollow interior, and ultrathin nanosheets.

PMID- 24924953
TI  - Guidelines for treating iron overload in myelodysplastic syndromes: a Taiwan
      consensus statement.
AB  - Iron overload is common in myelodysplastic syndrome (MDS) patients, and an
      accumulation of evidence shows that iron chelation may have benefits in these
      patients. However, discussion and consensus about iron chelation therapy (ICT)
      for MDS patients is lacking in Taiwan and other Southeast Asian countries. An
      Expert Panel in Taiwan was organized in 2011 to develop iron overload guidelines
      and provide a uniform reference for physicians treating MDS patients with iron
      overload, with specific regard to when to initiate ICT, in which patients, and
      the clinical and scientific rationale behind its use. 

PMID- 24924952
TI  - Effect of saponin on erythrocytes.
AB  - Saponins, naturally occurring glycosides and triterpene glycosides in plants, are
      considered useful in the prophylaxis and treatment of several disorders,
      including malignancy. The effect of these substances is partly attributable to
      induction of both apoptosis and necrosis. Saponin has previously been shown to
      trigger hemolysis. Erythrocytes may avoid hemolysis by entering programmed cell
      death or eryptosis, characterized by cell shrinkage and cell membrane scrambling,
      leading to phosphatidylserine exposure at the erythrocyte surface. Eryptosis is
      triggered by increase of cytosolic Ca(2+) activity ([Ca(2+)](i)). The present
      study explored, whether exposure of human erythrocytes to saponin modifies
      [Ca(2+)](i), ceramide formation, hemolysis, and eryptosis. Cell volume was
      estimated from forward scatter, phosphatidylserine exposure from annexin V
      binding, hemolysis from hemoglobin release, [Ca(2+)](i) from Fluo3-fluorescence,
      and ceramide utilizing specific antibodies. A 24 h exposure to saponin (15 ug/ml)
      resulted in a significant increase of annexin V binding and a significant
      stimulation of hemolysis. Saponin (15 ug/ml) further increased [Ca(2+)](i) and
      ceramide formation. Annexin V binding was significantly blunted but not abrogated
      in the nominal absence of extracellular Ca(2+). Saponin thus triggers cell
      membrane scrambling, an effect partially due to entry of extracellular Ca(2+) and
      ceramide formation.

PMID- 24924954
TI  - [Cutaneous sarcomas: update on selected fibrohistiocytic and myofibroblastic
      tumors].
AB  - BACKGROUND: Malignant fibrohistiocytic tumors are a heterogeneous group of
      mesenchymal neoplasms that may occur in the skin and subcutaneous tissues.
      DIAGNOSIS: Diagnosis of these tumors may be difficult, as they are rare, and a
      wide morphological diversity of types and subtypes has been described. In this
      update, relevant aspects of selected entities like dermatofibrosarcoma
      protuberans, desmoid tumor, atypical fibroxanthoma, pleomorphic dermal sarcoma,
      and myxofibrosarcoma are discussed according to the WHO classification of 2013.
      The typical clinical feature of these tumors is their mostly asymptomatic
      appearance. For diagnosis, the histologic workup is therefore the key feature;
      herein immunohistochemistry as well as molecular diagnostics become increasingly
      important. THERAPY: The primary treatment for locally resectable tumors is
      complete surgical removal; chemotherapy, radiation, and targeted therapies with
      kinase inhibitors are available for inoperable and metastatic disease.

PMID- 24924955
TI  - Fluorescence-guided surgery in combination with UVC irradiation cures metastatic
      human pancreatic cancer in orthotopic mouse models.
AB  - The aim of this study is to determine if ultraviolet light (UVC) irradiation in
      combination with fluorescence-guided surgery (FGS) can eradicate metastatic human
      pancreatic cancer in orthotopic nude-mouse models. Two weeks after orthotopic
      implantation of human MiaPaCa-2 pancreatic cancer cells, expressing green
      fluorescent protein (GFP), in nude mice, bright-light surgery (BLS) was performed
      on all tumor-bearing mice (n = 24). After BLS, mice were randomized into 3
      treatment groups; BLS-only (n = 8) or FGS (n = 8) or FGS-UVC (n = 8). The
      residual tumors were resected using a hand-held portable imaging system under
      fluorescence navigation in mice treated with FGS and FGS-UVC. The surgical
      resection bed was irradiated with 2700 J/m2 UVC (254 nm) in the mice treated with
      FGS-UVC. The average residual tumor area after FGS (n = 16) was significantly
      smaller than after BLS only (n = 24) (0.135+/-0.137 mm2 and 3.338+/-2.929 mm2,
      respectively; p = 0.007). The BLS treated mice had significantly reduced survival
      compared to FGS- and FGS-UVC-treated mice for both relapse-free survival (RFS)
      (p<0.001 and p<0.001, respectively) and overall survival (OS) (p<0.001 and
      p<0.001, respectively). FGS-UVC-treated mice had increased RFS and OS compared to
      FGS-only treated mice (p = 0.008 and p = 0.025, respectively); with RFS lasting
      at least 150 days indicating the animals were cured. The results of the present
      study suggest that UVC irradiation in combination with FGS has clinical potential
      to increase survival. 

PMID- 24924956
TI  - Perceptions of Heavy-Drinking College Students About a Sleep and Alcohol Health
      Intervention.
AB  - The purpose of this mixed methods study was to describe the sleep and
      psychological characteristics of heavy-drinking college students, their
      perceptions of sleep and sleep/alcohol interactions, and their reactions to a
      proposed integrated sleep and alcohol Web-based intervention. Students (N = 24)
      completed standardized surveys and participated in semistructured focus group
      interviews. Participants reported a high degree of sleep disturbance, sleep
      obstacles, and sleep-related consequences, which were validated by both
      quantitative and qualitative investigations. Sleep disturbance and sleep-related
      impairment were associated with more frequent drinking and greater risks from
      drinking. Participants perceived that alcohol has positive and negative effects
      on sleep latency, continuity, and quality. They expressed overall enthusiasm for
      the intervention but had specific content and format preferences.

PMID- 24924957
TI  - Quantification of metallothioneins in the earthworm by lomefloxacin-europium(iii)
      fluorescent probe.
AB  - A new fluorimetric method was established for the determination of trace amounts
      of metallothioneins (MT) in earthworm, using a lomefloxacin-europium(iii) (LMLX
      Eu(3+)) complex as a fluorescent probe. In a pH 6.5 Tris-HCl buffer solution, MT
      can markedly decrease the fluorescence intensity of LMLX-Eu(3+) at lambda = 613
      nm, and the magnitude of the decrease in this intensity was in direct proportion
      to the concentration of MT. The linear range was 0.08-20 mg L(-1) with a
      detection limit of 0.022 mg L(-1), and the recovery was in the range of 91.9
      104.4%. The results show that the fluorimetric method is relatively accurate and
      sensitive to measurements of concentration for MT over a wide range. This method
      has been successfully applied to the determination of the concentration of MT
      induced by heavy metal ions (Cd(2+), Pb(2+), Cu(2+), Zn(2+)) in Eisenia andrei.
      The amount of MT increased significantly in a dose-dependent manner to the heavy
      metal exposure, and these proteins can be used as biomarkers to assess the impact
      of heavy-metal contamination in soils. The method offered high sensitivity as
      well as accuracy with simple instrumentation and is suitable for direct
      quantification of total MT in Eisenia andrei.

PMID- 24924959
TI  - RCVS to revise its guidance on 24-hour cover.

PMID- 24924960
TI  - Bovine TB: test, vaccinate, remove project gets underway in Northern Ireland.

PMID- 24924958
TI  - Changes in immunological profile as a function of urbanization and lifestyle.
AB  - Differences in lifestyle and break with natural environment appear to be
      associated with changes in the immune system resulting in various adverse health
      effects. Although genetics can have a major impact on the immune system and
      disease susceptibility, the contribution of environmental factors is thought to
      be substantial. Here, we investigated the immunological profile of healthy
      volunteers living in a rural and an urban area of a developing African country
      (Senegal), and in a European country (the Netherlands). Using flow cytometry, we
      investigated T helper type 1 (Th1), Th2, Th17, Th22 and regulatory T cells, as
      well as CD4(+) T-cell and B-cell activation markers, and subsets of memory T and
      B cells in the peripheral blood. Rural Senegalese had significantly higher
      frequencies of Th1, Th2 and Th22 cells, memory CD4(+) T and B cells, as well as
      activated CD4(+) T and B cells compared with urban Senegalese and urban Dutch
      people. Within the Senegalese population, rural paritcipants displayed
      significantly higher frequencies of Th2 and Th22 cells, as well as higher pro
      inflammatory and T-cell activation and memory profiles compared with the urban
      population. The greater magnitude of immune activation and the enlarged memory
      pool, together with Th2 polarization, seen in rural participants from Africa,
      followed by urban Africans and Europeans suggest that environmental changes may
      define immunological footprints, which could have consequences for disease
      patterns in general and vaccine responses in particular. 

PMID- 24924961
TI  - AHVLA invites tenders for a range of veterinary services.

PMID- 24924962
TI  - Ketamine and tramadol reclassified.

PMID- 24924963
TI  - Model developed for ranking potentially pandemic flu viruses.

PMID- 24924964
TI  - AHVLA seeks views on full cost recovery plans.

PMID- 24924965
TI  - Tackling important issues in Europe.
AB  - Forthcoming animal health legislation, antimicrobial resistance and corporate
      practice were all discussed at the recent general assembly of the Federation of
      Veterinarians of Europe. Karin de Lange reports.

PMID- 24924966
TI  - Antibiotic use in animals in Europe.

PMID- 24924967
TI  - RVC academic features in diversity project.

PMID- 24924968
TI  - Bovine TB infection status in cattle in Great Britain in 2012.
AB  - This report, provided by the AHVLA, summarises the infection status of bovine
      tuberculosis (TB) in cattle in Great Britain from January 1 to December 31, 2012
      and describes some of the temporal trends observed over a longer period. The
      AHVLA intends to produce similar reports for future years to provide a concise
      summary of how the situation is developing. 

PMID- 24924969
TI  - Surgical or medical management of pyothorax in dogs?

PMID- 24924970
TI  - Bovine TB controls.

PMID- 24924971
TI  - Abortion in flocks vaccinated against enzootic abortion.

PMID- 24924972
TI  - Testing for exclusion of notifiable diseases.

PMID- 24924973
TI  - Complication following a brachial plexus block.

PMID- 24924974
TI  - Non-stun slaughter.

PMID- 24924975
TI  - Association between group 2 innate lymphoid cells enrichment, nasal polyps and
      allergy in chronic rhinosinusitis.
AB  - BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were shown to be involved in
      the initiation and coordination of Th2-type immune responses in allergic disease
      animal models. Recently, ILC2s enrichment was noted in chronic rhinosinusitis
      (CRS) patients; however, the role of ILC2s in coordinating the Th2 response in
      CRS remains to be elucidated. Here, we characterize the ILC2 compartment in CRS
      by investigating the correlations between ILC2s, Th2 cells and Th2 cytokines
      expression in CRS patients. METHODS: We used flow cytometric analysis of
      sinonasal mucosal tissues of 29 CRS patients and 5 controls to quantify ILC2s and
      Th2 cells. Messenger RNA expression levels of IL-5, IL-13, IL-25, IL-33, TSLP and
      GATA3 were determined using qRT-PCR. RESULTS: ILC2s were significantly enriched
      in nasal polyps (CRSwNP) patients. Multivariate linear regression showed a
      significant positive association of ILC2 numbers with CRSwNP and allergic CRS and
      a negative association with the number of previous endoscopic sinus surgeries.
      Group 2 innate lymphoid cell numbers significantly correlated with Th2 cell
      frequencies. Messenger RNA expression levels of IL-5 and IL-13 were increased in
      CRSwNP compared with controls, while mRNA levels of IL-25 and GATA3 were
      significantly reduced. CONCLUSIONS: Our results characterize the complex
      interactions between ILC2s and other Th2 response elements in the context of CRS
      and suggest that ILC2 enrichment occurs in CRSwNP and in allergic CRS patients.

PMID- 24924976
TI  - Caspase activation, hydrogen peroxide production and Akt dephosphorylation occur
      during stallion sperm senescence.
AB  - To investigate the mechanisms inducing sperm death after ejaculation, stallion
      ejaculates were incubated in BWW media during 6 h at 37 degrees C. At the
      beginning of the incubation period and after 1, 2, 4 and 6 h sperm motility and
      kinematics (CASA), mitochondrial membrane potential and membrane permeability and
      integrity were evaluated (flow cytometry). Also, at the same time intervals,
      active caspase 3, hydrogen peroxide, superoxide anion (flow cytometry) and Akt
      phosphorylation (flow cytometry) were evaluated. Major decreases in sperm
      function occurred after 6 h of incubation, although after 1 h decrease in the
      percentages of motile and progressive motile sperm occurred. The decrease
      observed in sperm functionality after 6 h of incubation was accompanied by a
      significant increase in the production of hydrogen peroxide and the greatest
      increase in caspase 3 activity. Additionally, the percentage of phosphorylated
      Akt reached a minimum after 6 h of incubation. These results provide evidences
      that sperm death during in vitro incubation is largely an apoptotic phenomena,
      probably stimulated by endogenous production of hydrogen peroxide and the lack of
      prosurvival factors maintaining Akt in a phosphorylated status. Disclosing
      molecular mechanisms leading to sperm death may help to develop new strategies
      for stallion sperm conservation.

PMID- 24924977
TI  - Correlation between behavioral and neuronal activities of toads Bufo bufo (L.) in
      response to moving configurational prey stimuli.
AB  - Common toads are able to distinguish prey objects from predators and behaviorally
      irrelevant stimuli by their shape and direction of motion. Using computer
      programs for correlation analysis, the prey-catching activity in response to
      different moving configurational stimuli was compared with the activity of
      neurons recorded at different levels of the visual pathway. Among retinal
      ganglion cells, the class R2 neurons were found to be most sensitive, to moving
      configurational stimuli. Among neurons recorded from retinal projection fields in
      the optic tectum and thalamic pretectal region, the tectal T5(2) neurons
      exhibited configurational selectivity. The output of these neurons showed the
      best positive correlation with prey-catching when both the neuronal and
      behavioral activities were compared in response to stripes of different length
      moving with their axis in, or perpendicular to, the direction of motion. 

PMID- 24924978
TI  - Relationships between the daily variations of social behavior and of plasma FSH,
      LH and testosterone levels in the domestic duck Anas platyrhynchos L.
AB  - The daily variations of plasma follicle-stimulating hormone (FSH), luteinizing
      hormone (LH) and testosterone were studied in three groups of 10-12 male domestic
      ducks at different times in their reproductive cycle. Rapid and significant
      changes in the mean plasma hormone levels were observed in each case but no
      reproducible pattern of daily variation could be defined. Before being submitted
      to repeated blood sampling, the birds were observed for their social behavior on
      several days from dawn to dusk. The frequencies of social displays and sexual
      behavior also changed significantly during the day but, once again, the pattern
      of changes was different from one case to another. There was, however, some
      indication that the pattern of daily changes could be a function of the season.
      The study of the relationships between the daily changes in behavior and in
      plasma hormone levels revealed several significant positive correlations. The
      variations in plasma FSH and/or testosterone are correlated with the variations
      in social displays and sexual behavior. Furthermore the same correlations could
      be detected in different groups of animals which had otherwise completely
      different patterns of daily variations. This suggests that the short-term changes
      in behavior could be controlled by these hormones, but it is still unclear
      whether the changes in hormone levels can cause behavioral changes within hours
      rather than the converse. 

PMID- 24924979
TI  - Choice of side of resting position in Vulpes vulpes (L.).
AB  - In fifteen foxes held under laboratory conditions all behaviour data recorded
      were tested according to the foxes' resting positions and especially as to the
      direction in which the body lay curled up (to the right or the left). 29 055
      single items of data could be extracted and processed statistically. All
      individuals taken together show a significant preference for the right direction
      in the resting position. If the data are separated according to sex the
      statistical significance is restricted to the males. The difference between males
      and females is significant. The analysis indicated individual differences;
      individual disposition with regard to preference for one side seems plausible.
      Statistical testing of the foxes by twos indicated variations correlated with the
      biosocial status. The dominance value is positively correlated with the tendency
      to prefer a resting position to the left. There are significant differences
      between two times of day (09.00-11.00; 17.00-19.00 h) and two times of year
      (December-March; June-August) with respect to the type of behaviour studied.
      These differences refer to mean values and variance. 

PMID- 24924980
TI  - Inhibition of control role behaviors in captive vervet monkeys (Cercopithecus
      aethiops sabaeus).
AB  - A captive vervet monkey (Cercopithecus aethiops sabaeus) colony was divided into
      subgroups to determine the influence of the control male and the control female
      on the expression of control role behaviors in other group members. Separation
      from the control male invariably caused an increase in the control male factor
      score for other adult and subadult males in the colony, and reunion caused a
      decline to baseline. Separation from the control female produced no consistent
      behavioral effect in other adult females. 

PMID- 24924981
TI  - A strategy approach to the study of primate dominance behaviour.
AB  - It is argued that the concept of social dominance is likely to be a useful
      explanatory principle in a theory of primate social behaviour. This argument
      depends on switching from a concern with the structure of primate hierarchies to
      looking at the process of attaining/ maintaining a given rank position in the
      hierarchy; and on a switch from the exclusive focusing on dyadic interactions to
      the inclusion of multi-animal interactions in studies of dominance behaviour.
      This produces what in this paper is termed the 'strategy approach' to the study
      of primate dominance behaviour. Its potential explanatory utility lies in its
      prediction of change in affiliative relationships in the social group. 

PMID- 24924982
TI  - Cardiac responses in alarmed red deer calves.
AB  - Radio transmitters were used to record the ECG signals of young red deer calves
      (Cervus elaphus) when they were exposed to various stimuli which elicited the
      immobility or "freezing" response. When the calves were exposed to stimuli likely
      to occur in the deer's natural habitat, the heart rate decreased by 25 to 85% of
      the pre-exposure rate. The calves displayed a more pronounced bradycardia during
      their first days of life than at a later age. There are also indications that
      repeated exposure to the same stimulus will cause a gradual waning both of the
      bradycardia and of the behavioural response. 

PMID- 24924992
TI  - Acting on minimal residual disease in ALL.

PMID- 24924991
TI  - Augmented post-remission therapy for a minimal residual disease-defined high-risk
      subgroup of children and young people with clinical standard-risk and
      intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised
      controlled trial.
AB  - BACKGROUND: No randomised study has shown whether stratification of treatment by
      minimal residual disease (MRD) response improves outcome in children and young
      people with acute lymphoblastic leukaemia (ALL). We assessed whether children and
      young people with clinical standard and intermediate-risk ALL who have persistent
      MRD at the end of induction therapy benefit from augmented post-remission
      therapy. METHODS: Between Oct 1, 2003, and June 30, 2011, we enrolled eligible
      patients aged 1-24 years and initially categorised them into clinical standard
      risk, intermediate-risk, and high-risk groups on the basis of a combination of
      National Cancer Institute criteria, cytogenetics, and early morphological
      response to induction therapy. Clinical standard-risk and intermediate-risk
      patients with MRD of 0.01% or higher at day 29 of induction (MRD high risk) were
      randomly assigned (1:1) to standard therapy (treatment regimens A and B) or
      augmented post-remission therapy (regimen C). Compared with standard therapy, the
      augmented treatment regimen (regimen C) included an additional eight doses of
      pegylated asparaginase, 18 doses of vincristine, and escalated-dose intravenous
      methotrexate without folinic acid rescue during interim maintenance courses.
      Computer randomisation was used for treatment allocation and was balanced for
      sex, age (<10 years vs >=10 years), and white blood cell count at diagnosis (<50
      * 10(9)/L vs >=50 * 10(9)/L) by minimisation. Patients, clinicians, and data
      analysts were not masked to treatment allocation. The primary outcomes were event
      free survival and overall survival. Analyses were by intention to treat. This
      trial is registered with Current Controlled Trials, number ISRCTN07355119.
      FINDINGS: 533 MRD high-risk patients were randomly assigned to receive standard
      (n=266) or augmented (n=267) post-remission therapy. After a median follow-up of
      70 months (IQR 52-91), 5-year event-free survival was better in the augmented
      treatment group (89.6% [95% CI 85.9-93.3]) than in the standard group (82.8%
      [78.1-87.5]; odds ratio [OR] 0.61 [95% CI 0.39-0.98], p=0.04). Overall survival
      at 5 years was numerically, but not significantly, higher in the augmented
      treatment group (92.9% [95% CI 89.8-96.0]) than in the standard therapy group
      (88.9% [85.0-92.8]; OR 0.67 [95% CI 0.38-1.17], p=0.16). More adverse events
      occurred in the augmented treatment group than in the standard group
      (asparaginase-related hypersensitivity in 18 [6.7%] in the augmented group vs two
      [0.8%] in the standard group and asparaginase-related pancreatitis in eight
      [3.0%] vs one [0.4%]; intravenous methotrexate-related mucositis in 11 [4.1%] vs
      three [1.1%] and methotrexate-related stomatitis in 48 [18.0%] vs 12 [4.5%]).
      INTERPRETATION: Our findings suggest that children and young people with acute
      lymphoblastic leukaemia and 0.01% or more MRD at the end of remission induction
      therapy could benefit from augmented post-remission therapy. However, the
      asparaginase and intravenous methotrexate used in the augmented treatment regimen
      is associated with more adverse events than is the standard post-remission
      treatment regimen. FUNDING: Medical Research Council and Leukaemia and Lymphoma
      Research.

PMID- 24924993
TI  - Home blood pressure monitoring: primary role in hypertension management.
AB  - In the last two decades, considerable evidence on home blood pressure monitoring
      has accumulated and current guidelines recommend its wide application in clinical
      practice. First, several outcome studies have shown that the ability of home
      blood pressure measurements in predicting preclinical target organ damage and
      cardiovascular events is superior to that of the conventional office blood
      pressure measurements and similar to that of 24-hour ambulatory monitoring.
      Second, cross-sectional studies showed considerable agreement of home blood
      pressure measurements with ambulatory monitoring in detecting the white-coat and
      masked hypertension phenomena, in both untreated and treated subjects. Third,
      studies have shown larger blood pressure decline by using home blood pressure
      monitoring instead of office measurements for treatment adjustment. Fourth, in
      treated hypertensives, home blood pressure monitoring has been shown to improve
      long-term adherence to antihypertensive drug treatment and thus, has improved
      hypertension control rates. These data suggest that home blood pressure should no
      longer be regarded as only a screening tool that requires confirmation by
      ambulatory monitoring. Provided that an unbiased assessment is obtained according
      to current recommendations, home blood pressure monitoring should have primary
      role in diagnosis, treatment adjustment, and long-term follow-up of most cases
      with hypertension. 

PMID- 24924994
TI  - The role of adiponectin in endothelial dysfunction and hypertension.
AB  - It has been two decades since the discovery of adiponectin, and today its role in
      insulin resistance, inflammation, and atherosclerosis are areas of major
      interest. Production of adiponectin is reduced in all inflammatory processes and
      states of insulin resistance such as obesity, type 2 diabetes mellitus, and
      coronary artery disease. Adiponectin regulates carbohydrate metabolism, and may
      also regulate vascular homeostasis by affecting important signaling pathways in
      endothelial cells and modulating inflammatory responses in the subendothelial
      space. Clinical studies have demonstrated a relationship between serum
      adiponectin concentrations and the activity of the renin-angiotensin-aldosterone
      system (RAAS), causing changes in blood pressure. Antihypertensive therapy with
      angiotensin II receptor blockers (ARBs) has been demonstrated to increase
      adiponectin levels in 3-6 months. Adiponectin has also been shown to play a role
      in cardiac injury in modulation of pro-survival reactions, cardiac energy
      metabolism, and inhibition of hypertrophic remodeling. The effects of adiponectin
      on the cardiovascular system are believed to be partially mediated by the
      activation of 5' adenosine monophosphate-activated protein kinase (AMPK) and
      cyclooxygenase-2 (COX-2) pathways, reducing endothelial cell apoptosis, promoting
      nitric oxide production, decreasing tumor necrosis factor-alpha (TNF-alpha)
      activity, and preventing atherosclerotic proliferation and smooth muscle cell
      migration. Further evaluation of biologically active forms of adiponectin and its
      receptor should help to clarify how obesity affects the cardiovascular system. 

PMID- 24924995
TI  - Sodium, potassium, blood pressure, and cardiovascular disease in humans.
AB  - The scientific underpinning for recommended levels of dietary sodium and
      potassium intake is of great importance to healthcare providers and policy
      decision-makers. Recent clinical trials and meta-analyses confirm the capacity of
      dietary sodium reduction and potassium supplementation to reduce blood pressure
      with no harmful effects on blood lipid levels in customary clinical settings.
      Blood pressure is thought to be a good surrogate for cardiovascular disease
      events and the most important preventable risk factor for mortality and
      disability-adjusted life years. Cohort analyses and related pooling studies that
      have been used to explore the relationship between dietary Na and CVD were all
      based on secondary analyses of datasets that were not designed for this purpose.
      Most are of insufficient quality to provide dependable information. The limited
      information available from clinical trial experience and cohort studies of higher
      quality suggests a reduction in dietary Na decreases CVD morbidity and mortality.
      Modeling studies suggest that a small reduction in dietary sodium would result in
      a sizable general population health benefit. Some countries have experienced a
      progressive decline in average dietary sodium consumption. However, there is no
      evidence of a corresponding trend in the United States, and almost the entire
      population is failing to meet dietary sodium and potassium guideline
      recommendations. 

PMID- 24924996
TI  - Molecular epidemiology and clinical features of human T cell lymphotropic virus
      type 1 infection in Spain.
AB  - Human T cell lymphotropic virus type 1 (HTLV-1) infection in Spain is rare and
      mainly affects immigrants from endemic regions and native Spaniards with a prior
      history of sexual intercourse with persons from endemic countries. Herein, we
      report the main clinical and virological features of cases reported in Spain. All
      individuals with HTLV-1 infection recorded at the national registry since 1989
      were examined. Phylogenetic analysis was performed based on the long terminal
      repeat (LTR) region. A total of 229 HTLV-1 cases had been reported up to December
      2012. The mean age was 41 years old and 61% were female. Their country of origin
      was Latin America in 59%, Africa in 15%, and Spain in 20%. Transmission had
      occurred following sexual contact in 41%, parenteral exposure in 12%, and
      vertically in 9%. HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP) was diagnosed in 27 cases and adult T cell leukemia/lymphoma (ATLL) in
      17 subjects. HTLV-1 subtype could be obtained for 45 patients; all but one
      belonged to the Cosmopolitan subtype a. One Nigerian pregnant woman harbored HTLV
      1 subtype b. Within the Cosmopolitan subtype a, two individuals (from Bolivia and
      Peru, respectively) belonged to the Japanese subgroup B, another two (from
      Senegal and Mauritania) to the North African subgroup D, and 39 to the
      Transcontinental subgroup A. Of note, one divergent HTLV-1 strain from an
      Ethiopian branched off from all five known Cosmopolitan subtype 1a subgroups.
      Divergent HTLV-1 strains have been introduced and currently circulate in Spain.
      The relatively large proportion of symptomatic cases (19%) suggests that HTLV-1
      infection is underdiagnosed in Spain.

PMID- 24924997
TI  - "3D fusion" echocardiography improves 3D left ventricular assessment: comparison
      with 2D contrast echocardiography.
AB  - BACKGROUND: Three-dimensional fusion echocardiography (3DFE) is a novel
      postprocessing approach that utilizes imaging data acquired from multiple 3D
      acquisitions. We assessed image quality, endocardial border definition, and
      cardiac wall motion in patients using 3DFE compared to standard 3D images (3D)
      and results obtained with contrast echocardiography (2DC). METHODS: Twenty-four
      patients (mean age 66.9 +/- 13 years, 17 males, 7 females) undergoing 2DC had
      three, noncontrast, 3D apical volumes acquired at rest. Images were fused using
      an automated image fusion approach. Quality of the 3DFE was compared to both 3D
      and 2DC based on contrast-to-noise ratio (CNR) and endocardial border definition.
      We then compared clinical wall-motion score index (WMSI) calculated from 3DFE and
      3D to those obtained from 2DC images. RESULTS: Fused 3D volumes had significantly
      improved CNR (8.92 +/- 1.35 vs. 6.59 +/- 1.19, P < 0.0005) and segmental image
      quality (2.42 +/- 0.99 vs. 1.93 +/- 1.18, P < 0.005) compared to unfused 3D
      acquisitions. Levels achieved were closer to scores for 2D contrast images (CNR:
      9.04 +/- 2.21, P = 0.6; segmental image quality: 2.91 +/- 0.37, P < 0.005). WMSI
      calculated from fused 3D volumes did not differ significantly from those obtained
      from 2D contrast echocardiography (1.06 +/- 0.09 vs. 1.07 +/- 0.15, P = 0.69),
      whereas unfused images produced significantly more variable results (1.19 +/-
      0.30). This was confirmed by a better intraclass correlation coefficient (ICC
      0.72; 95% CI 0.32-0.88) relative to comparisons with unfused images (ICC 0.56;
      95% CI 0.02-0.81). CONCLUSION: 3DFE significantly improves left ventricular image
      quality compared to unfused 3D in a patient population and allows noncontrast
      assessment of wall motion that approaches that achieved with 2D contrast
      echocardiography.

PMID- 24924998
TI  - Rights versus morality: online debate about decriminalization of gay sex in
      Singapore.
AB  - This article presents a quantitative content analysis of 10,473 comments from two
      opposing online petitions related to the legal status of a section of the penal
      code in Singapore used to ban sex between men. Results indicate numerous
      significant differences in how the two sides discussed the law and its
      significance. In particular, they used different types of arguments to support
      their views and expressed different kinds of concerns over the potential impact
      of changing or maintaining the law. The patterns of language use seem to reflect
      distinctly different approaches to the debate and suggest the difficulty of
      finding common ground amid this contentious social issue, but they also reveal
      similarities to how Western cultures have framed the debate. 

PMID- 24924999
TI  - Clinical utility of endorectal MRI-guided prostate biopsy: preliminary
      experience.
AB  - PURPOSE: To investigate the potential clinical utility of endorectal MRI-guided
      biopsy in patients with known or suspected prostate cancer. MATERIALS AND
      METHODS: We prospectively recruited 24 men with known or suspected prostate
      cancer in whom MRI-guided biopsy was clinically requested after multiparametric
      endorectal MRI showed one or more appropriate targets. One to six 18-gauge biopsy
      cores were obtained from each patient. Transrectal ultrasound guided biopsy
      results and post MRI-guided biopsy complications were also recorded. RESULTS: MRI
      guided biopsy was positive in 5 of 7 patients with suspected prostate cancer
      (including 2 of 4 with prior negative ultrasound-guided biopsies), in 8 of 12
      with known untreated prostate cancer (including 5 where MRI-guided biopsy
      demonstrated a higher Gleason score than ultrasound guided biopsy results), and
      in 3 of 5 with treated cancer. MRI-guided biopsies had a significantly higher
      maximum percentage of cancer in positive cores when compared with ultrasound
      guided biopsy (mean of 37 +/- 8% versus 13 +/- 4%; P = 0.01). No serious
      postbiopsy complications occurred. CONCLUSION: Our preliminary experience
      suggests endorectal MRI-guided biopsy may safely contribute to the management of
      patients with known or suspected prostate cancer by making a new diagnosis of
      malignancy, upgrading previously diagnosed disease, or diagnosing local
      recurrence.

PMID- 24925000
TI  - Interleaved diffusion-weighted improved by adaptive partial-Fourier and multiband
      multiplexed sensitivity-encoding reconstruction.
AB  - PURPOSE: We report a series of techniques to reliably eliminate artifacts in
      interleaved echo-planar imaging (EPI) based diffusion-weighted imaging (DWI).
      METHODS: First, we integrate the previously reported multiplexed sensitivity
      encoding (MUSE) algorithm with a new adaptive Homodyne partial-Fourier
      reconstruction algorithm, so that images reconstructed from interleaved partial
      Fourier DWI data are free from artifacts even in the presence of either (a)
      motion-induced k-space energy peak displacement, or (b) susceptibility field
      gradient induced fast phase changes. Second, we generalize the previously
      reported single-band MUSE framework to multiband MUSE, so that both through-plane
      and in-plane aliasing artifacts in multiband multishot interleaved DWI data can
      be effectively eliminated. RESULTS: The new adaptive Homodyne-MUSE reconstruction
      algorithm reliably produces high-quality and high-resolution DWI, eliminating
      residual artifacts in images reconstructed with previously reported methods.
      Furthermore, the generalized MUSE algorithm is compatible with multiband and high
      throughput DWI. CONCLUSION: The integration of the multiband and adaptive
      Homodyne-MUSE algorithms significantly improves the spatial-resolution, image
      quality, and scan throughput of interleaved DWI. We expect that the reported
      reconstruction framework will play an important role in enabling high-resolution
      DWI for both neuroscience research and clinical uses.

PMID- 24925002
TI  - [Management of stridor].
AB  - Pediatric stridor is usually due to benign laryngomalacia. This pathology of
      unknown origin usually heals spontaneously during the first 18 months of life.
      Mild laryngomalacia is characterized by normal weight growth, the absence of
      sleep apneas and of associated swallowing or neurological disorders. Medical
      treatment is sufficient to release symptoms. Severe clinical forms are more rare,
      representing about 10 % of cases. They require an endoscopic evaluation of the
      upper airway under general anesthesia, as well as an endoscopic
      suppraglottoplasty. Non-invasive ventilation is an interesting additional tool in
      case of surgical failures or in some infants with comorbid conditions.

PMID- 24925001
TI  - ERPs dissociate proactive and reactive control: evidence from a task-switching
      paradigm with informative and uninformative cues.
AB  - According to the dual mechanism of control (DMC) framework, cognitive control can
      be recruited proactively to prevent response conflict when advance preparation is
      feasible or is up-regulated to overcome response conflict after it is detected.
      This study aimed at empirically dissociating proactive and reactive control
      processes proposed by the DMC and identifying corresponding event-related
      potential (ERP) correlates. Behavioral and electrophysiological indices of
      cognitive control were measured during a task-switch paradigm with or without
      informative advance cues, in which proactive control was feasible or not.
      Proactive control was associated with a (right-) frontal sustained ERP modulation
      during the cue-target interval. In line with the successful recruitment of
      proactive control, informative, as compared with uninformative, cue conditions
      were associated with reduced behavioral and ERP correlates of conflict. ERP
      correlates of conflict were evident both during conflict detection upon target
      presentation (N(inc)) and during conflict resolution-in particular, following
      uninformative cues. Reactive control assumed to support conflict resolution was
      associated with a (left-) frontal transient preresponse ERP modulation for
      uninformative, but not informative, cue conditions. Together, these data suggest
      that complementary proactive and reactive control processes operate in concert to
      flexibly support goal-directed behavior in response to variable task-demands, by
      either preventing or resolving response conflicts, as they are detected or
      anticipated.

PMID- 24925003
TI  - Kinematics of the upper cervical spine during high velocity-low amplitude
      manipulation. Analysis of intra- and inter-operator reliability for pre
      manipulation positioning and impulse displacements.
AB  - To date, kinematics data analyzing continuous 3D motion of upper cervical spine
      (UCS) manipulation is lacking. This in vitro study aims at investigating inter-
      and intra-operator reliability of kinematics during high velocity low amplitude
      manipulation of the UCS. Three fresh specimens were used. Restricted dissection
      was realized to attach technical clusters to each bone (skull to C2). Motion data
      was obtained using an optoelectronic system during manipulation. Kinematics data
      were integrated into specific-subject 3D models to provide anatomical motion
      representation during thrust manipulation. The reliability of manipulation
      kinematics was assessed for three practitioners performing two sessions of three
      repetitions on two separate days. For pre-manipulation positioning, average UCS
      ROM (SD) were 10 degrees  (5 degrees ), 22 degrees  (5 degrees ) and 14 degrees 
      (4 degrees ) for lateral bending, axial rotation and flexion-extension,
      respectively. For the impulse phase, average axial rotation magnitude ranged from
      7 degrees  to 12 degrees . Reliability analysis showed average RMS up to 8
      degrees  for pre-manipulation positioning and up to 5 degrees  for the impulse
      phase. As compared to physiological ROM, this study supports the limited angular
      displacement during manipulation for UCS motion components, especially for axial
      rotation. Kinematics reliability confirms intra- and inter-operator consistency
      although pre-manipulation positioning reliability is slightly lower between
      practitioners and sessions. 

PMID- 24925004
TI  - Selection and improving of fit-for-purpose sampling procedures for specific foods
      and risks.

PMID- 24925005
TI  - Cytoskeleton of newborn vocal fold stellate cells.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold stellate cells (VFSCs) in the human maculae
      flavae located at both ends of the vocal fold mucosa are inferred to be involved
      in the metabolism of extracellular matrices of the vocal fold mucosa. Tension
      caused by phonation (vocal fold vibration) likely regulates the behavior of the
      VFSCs in the human maculae flava. Tensile and compressive strains have direct
      effects on cell morphology and structure, including changes in cytoskeletal
      structure and organization. Cytoskeletons play a role as mechanoreceptors for the
      cells. The microstructure of the intermediate filaments and the expression of
      their characteristic proteins were investigated regarding the human newborn
      VFSCs. STUDY DESIGN: Histopathologic analysis of the human newborn vocal fold.
      METHODS: Three newborn vocal fold mucosae were investigated by
      immunohistochemistry and electron microscopy. RESULTS: The intermediate filaments
      in the cytoplasm of the newborn VFSCs were few in number. However, their
      characteristic proteins (vimentin, desmin, GFAP [Glial fibrillary acidic
      protein], cytokeratin) had already expressed. CONCLUSION: The function and fate
      of VFSCs are regulated by various microenvironmental factors. Not only chemical
      factors but also mechanical factors could also modulate VFSC behaviors. The
      cytoskeletal structure of the newborn VFSCs is under development. And the newborn
      VFSCs have not acquired mechanical regulation. LEVEL OF EVIDENCE: N/A.

PMID- 24925006
TI  - Eradication strategy for persistent methicillin-resistant Staphylococcus aureus
      infection in individuals with cystic fibrosis--the PMEP trial: study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      respiratory infection in cystic fibrosis (CF) has increased dramatically over the
      last decade, and is now affecting approximately 25% of patients. Epidemiologic
      evidence suggests that persistent infection with MRSA results in an increased
      rate of decline in FEV1 and shortened survival. Currently, there are no
      conclusive studies demonstrating an effective and safe treatment protocol for
      persistent MRSA respiratory infection in CF. METHODS/DESIGN: The primary
      objective of this study is to evaluate the safety and efficacy of a 28-day course
      of vancomycin for inhalation in combination with oral antibiotics in eliminating
      MRSA from the respiratory tract of individuals with CF and persistent MRSA
      infection. This is a two-center, randomized, double-blind, comparator-controlled,
      parallel-group study with 1:1 assignment to either vancomycin for inhalation (250
      mg twice a day) or taste-matched placebo for 28 days in individuals with cystic
      fibrosis. In addition, both groups will receive oral rifampin, a second oral
      antibiotic - trimethoprim/sulfamethoxazole (TMP/SMX) or doxycycline, protocol
      determined - mupirocin intranasal cream, and chlorhexidine body washes. Forty
      patients with persistent respiratory tract MRSA infection will be enrolled: 20
      will be randomized to vancomycin for inhalation and 20 to a taste-matched
      placebo. The primary outcome will be the presence of MRSA in sputum respiratory
      tract cultures 1 month after the conclusion of treatment. Secondary outcomes
      include the efficacy of the intervention on: FEV1% predicted, patient reported
      outcomes, pulmonary exacerbations, and MRSA colony-forming units found in
      respiratory tract sample culture. DISCUSSION: Results of this study will provide
      guidance to clinicians regarding the safety and effectiveness of a targeted
      eradication strategy for persistent MRSA infection in CF. TRIAL REGISTRATION:
      This trial is registered at ClinicalTrials.gov (NCT01594827, received 05/07/2012)
      and is funded by the Cystic Fibrosis Foundation (Grants: PMEP10K1 and PMEP11K1).

PMID- 24925007
TI  - Second-order control of sequence-class equivalences in children.
AB  - Children learned matching-to-sample tasks to establish two equivalence classes.
      Then, one member from each class appeared in a sequence procedure, thereby
      acquiring the ordinal properties "first" and "second". When the remaining members
      in the two equivalence classes were placed in the sequence context, subjects
      responded in appropriate order without additional training. The data suggest a
      basic mechanism which can account for the production of new sequence behavior
      which has no explicit history of training. 

PMID- 24925008
TI  - Conspecific vocalisations, tonic immobility and fearfulness in the domestic fowl.
AB  - Vocalisation is important in the transmission of fear/alarm among chickens. In
      this experiment, therefore, the effects of various conspecific calls on tonic
      immobility, a fear-potentiated, anti-predator response, were examined in adult
      laying hens. The shortest durations of immobility were observed after exposure to
      recordings of either the familiar background noise of the poultry house of 'Ku'
      calls which are normally associated with feeding. These stimuli exerted similar
      effects and both are considered more likely to attenuate rather than heighten
      fearfulness. Intermediate levels of immobility followed presentation of the post
      laying cackle whereas recordings of warning calls, such as the aerial predator
      call, the ground predator call or the fear squawk, all significantly prolonged
      tonic immobility. The biological significance of these results is discussed in
      terms of fear and predator-defence. 

PMID- 24925009
TI  - Strain differences in parturition behavior and survival probability in rats
      (Rattus Norvegicus).
AB  - Three strains of laboratory rats (Wu:Cpb, CPB-B and WKY/Cpb) differing widely in
      reproductive success were compared concerning the role played by maternal
      behavior in the survival probability of pups. Parturition behavior of the dams
      was selected for study as pups are most dependent on the mother's behavior at,
      and immediately after birth. Great strain differences in survival rate of life
      born pups were found. However, differences between strains in parturition
      behavior were found to be restricted to only one pup oriented behavior and some
      non social behaviors. Besides no pups died at the day of birth nor did it seem
      probable that the strain differences we found in parturition behavior can be held
      responsible for the eventual death of pups during parturition. The suggestion is
      presented that strain differences in maternal behavior which affect survival
      chances of pups are to be looked for in the lactation period. 

PMID- 24925010
TI  - An automated photographic technique for behavioural investigations of social
      insects.
AB  - We describe a technique based on automatic photography as an alternative to the
      visual scanning method for behavioural investigations of insect societies. This
      technique opens up the possibilities for studying poorly-populated colonies over
      prolonged periods. The reliability of this technique as compared to the direct
      observational method was demonstrated on the basis of an investigation of the
      social organization of a neotropical Ponerine ant (Ectatomma ruidum ). The
      results obtained by the two techniques were very comparable both in regards to
      the overall behavioural profiles for the colony and as concerns the description
      of functional groups and sub-castes. 

PMID- 24925011
TI  - Seasonal variations in habitat selection and spatial distribution of wild boar
      (Sus Scrofa) in the Camargue, Southern France.
AB  - Seasonal habitat selection and use by wild boars were studied in relation to
      major vegetation cover types and flooded areas, on a sampling area of 1047 ha.
      Six habitat types were delineated: "sansouire" (local name), "enganes" (local
      name), halophytic grasslands, scrub grasslands, deep and shallow marshes, fallow
      or cultivated farmlands. Once a season in 1982, this sampling area was
      systematically examined and mapped for wild boar signs left in the following
      places : bedding places, farrowing nests, wallows, rubbing trees and rooting
      sites. Marshes are the most frequently used areas throughout the year since all
      activities can be conducted there. Scrub grasslands, although less common, are
      also important, because of scrubs of Phillyrea angustifolia used for resting and
      dense groves of Ulmus campestris used for rubbing. Rooting activity,
      predominantly done in marshes, is also conducted in all types of grasslands (even
      cultivated) during the winter, and in farmlands during the summer. In the
      sampling area, seasonal variations in the counts of activity signs as well as in
      the number of wild boar sightings suggest correlated variations of density. The
      estimated autumn to spring density is higher (2.5-2.9 animals/km2) than the
      summer one (0.6 animals/km2). These seasonal variations are explained by spatial
      adjustments according to environmental conditions. In the early warm season,
      drying out of marshes and soils in the study area leads to emigration of part of
      population onto neighbouring grounds where agricultural crops are available.
      Return movements are presumably causally related to different factors : onset of
      the rains, hunting disturbance and harvest of crops. Fluctuations of
      environmental factors require a flexible strategy of habitat utilization. We
      propose a model for the organization of wild boar populations, which would be
      formed by "nuclei" presenting environment-dependent densities. 

PMID- 24925012
TI  - An experimental analysis of "empathic" response: Effects of pain reactions of
      pigeon upon other pigeon's operant behavior.
AB  - Suppression of operant behavior by exposure to pain reactions of conspecifics was
      examined with pigeons. Three groups of pigeons were trained on a VI schedule, and
      were then exposed to the pain reactions of an adjoining bird to electric shocks.
      Although every subject showed suppression of responding, the suppression
      decreased with repeated exposures. Following this assessment, a conditioning
      group received conditioned suppression training in which the pain reaction of the
      adjoining bird was the CS and an electric shock was the US; a shock exposure
      group received the electric shock without any explicit CS; and, a no-shock group
      did not receive any shock. After these treatments, every group was exposed to the
      pain reactions of the adjoining bird (test 1). The conditioning group and the
      shock exposure group showed clear suppression in responding, but the no-shock
      group did not. The no-shock group then received the shock exposure treatment and
      the conditioned suppression training succesively, and the shock exposure group
      received the conditioned suppression training. Results of tests with the pain
      reaction of the adjoining bird supported the results of the test 1, however,
      suppression caused by the shock exposure was not so clear in the no-shock group.
      The present results demonstrated that conspecific behavior can become a CS by
      conditioned suppression training, and, the behavior to an aversive stimulus can
      acquire aversive properties for other conspecifics when they have shared the
      exposure to the same aversive stimulus. 

PMID- 24925013
TI  - Post partum aggression against intruding male conspecifics in sprague-dawley
      rats.
AB  - Six independent groups of individually housed female rats of the Sprague-Dawley
      strain were given a 5-min aggression test on Day 0 (day of parturition), 3, 6, 9,
      12, or 15 postpartum. Latency to attack male conspecifics differed reliably among
      groups, being shortest on Day 0. Significant group differences in frequency of
      aggressive acts were also found with a consistent reduction in all measures by
      the end of the second week of lactation. Although attack by females caused most
      male intruders to react defensively, 23% of intruders showed retaliatory attacks
      against females. The function of maternal aggression in protecting the pups from
      infanticide by unfamiliar males is discussed. 

PMID- 24925014
TI  - The swimming activity of the staggerer mutant mouse.
AB  - Four experiments investigated the swimming behaviour of staggerer mutant mice.
      The results partially confirmed previous reports that a mouse's swimming is
      unaffected by the staggerer mutation. In terms of speed and distance there are
      indeed no measurable differences between normal and staggerer mice, when first
      placed in the water. The stagger's resistance was however shown to be much lower
      than a normal's and the genetic difference was also associated with different
      styles of swimming. Furthermore, whereas the normal mouse's swimming behaviour
      evolves with increased time in the water, the staggerer's remains constant. The
      differences are interpreted on the basis of abnormal novelty reactions by the
      staggerer mutants. Thus, swimming appears to be a better tool for investigating
      the higher-level cognitive functions of this mutant than terrestrial locomotion. 

PMID- 24925021
TI  - Vascular soft-tissue sarcomas: a prognostic model from a retrospective single
      center study.
AB  - BACKGROUND: Vascular soft-tissue sarcomas are a rare form of sarcoma. Malignant
      subtypes exhibit a variety of biological behaviors. We describe the
      clinicopathological characteristics and patient survival outcomes of malignant
      vascular soft-tissue sarcomas. METHODS: We conducted a retrospective study on a
      cohort of 84 patients diagnosed with vascular tumors by histological examination
      at the Yonsei University College of Medicine between April 1987 and August 2011.
      The primary end point was overall survival (OS). RESULTS: The angiosarcoma
      patients had a significantly shorter OS than the patients with other subtypes of
      sarcomas (59.0 and 142.7 months, respectively; p < 0.001). Upon multivariate
      analysis of survival in patients who underwent surgical resection, the following
      independent prognostic factors were identified: primary site (trunk, p = 0.001),
      age (older than 65 years, p < 0.001), pathology (angiosarcoma, p = 0.006) and R2
      resection (p = 0.002). CONCLUSION: The independent prognostic factors for shorter
      survival are the trunk as the primary site, malignant angiosarcoma and age (>65
      years). Complete excision should be attempted for providing a survival advantage
      in the patients with localized disease. In addition, bleeding episodes are much
      more frequent in patients with a poor survival outcome.

PMID- 24925022
TI  - IV prenatal nicotine exposure increases the reinforcing efficacy of
      methamphetamine in adult rat offspring.
AB  - BACKGROUND: Maternal smoking during pregnancy is correlated with increased
      substance use in offspring. Research using rodent models shows that gestational
      nicotine exposure produces enduring alterations in the neurodevelopment of
      motivational systems, and that rats prenatally treated with nicotine have altered
      motivation for drug reinforcement on fixed-ratio (FR) schedules of reinforcement.
      OBJECTIVE: The present study investigated methamphetamine (METH) self
      administration in adult offspring prenatally exposed to intravenous (IV) nicotine
      or saline using a progressive-ratio (PR) schedule of reinforcement. METHODS:
      Pregnant rats were administered IV prenatal saline (PS) or nicotine (PN;
      0.05mg/kg/infusion), 3*/day during gestational days 8-21. At postnatal day 70,
      offspring acquired a lever-press response for sucrose (26%, w/v; FR1-3). Rats
      were trained with METH (0.05mg/kg/infusion), and following stable FR responding,
      animals were tested using a progressive-ratio (PR) schedule for three different
      doses of METH (0.005, 0.025, and 0.05mg/kg/infusion). RESULTS: METH infusion,
      active lever presses, and the ratio breakpoint are reported. PN-exposed animals
      exhibited more METH-maintained responding than PS controls, according to a
      dose*prenatal treatment interaction (e.g., infusions). PN rats self-administered
      more METH infusions between the range of 0.025 and 0.05, but not for the
      0.005mg/kg/infusion dose. CONCLUSIONS: IV PN-exposure produced enhanced
      motivation to self-administer METH. These findings indicate that pregnant women
      who smoke tobacco may impart neurobiological changes in offspring's motivational
      systems that render them increasingly vulnerable to drug abuse during adulthood.

PMID- 24925023
TI  - TAAR1-dependent effects of apomorphine in mice.
AB  - G protein-coupled trace amine-associated receptor 1 (TAAR1) is expressed in
      several brain regions and modulates dopaminergic activity partially by affecting
      D2 dopamine receptor function. In vitro, the nonselective dopamine agonist
      apomorphine can activate mouse and rat TAAR1. The aim of the present study was to
      evaluate whether apomorphine activity at the rodent TAAR1 observed in in vitro
      studies contributes to its behavioral manifestation in mice. For this purpose, we
      compared the behavioral effects of a wide range of apomorphine doses in wild type
      (WT) and TAAR1 knockout (TAAR1-KO) mice. Apomorphine-induced locomotor responses
      (0.01-4.0 mg/kg) were tested in locomotor activity boxes, and stereotypic
      behavior at 5 mg/kg was tested by ethological methods. A gnawing test was used to
      analyze the effects of the highest dose of apomorphine (10 mg/kg). No
      statistically significant differences were observed between TAAR1-KO and WT mice
      following inhibitory pre-synaptic low doses of apomorphine. At higher doses (2.0
      5.0 mg/kg), apomorphine-induced climbing behavior was significantly reduced in
      TAAR1 mutants relative to WT controls. Moreover, the lack of TAAR1 receptors
      decreased certain types of stereotypies (as reflected in by measures of the
      global stereotypy score, licking but not sniffing or gnawing) that were induced
      by high doses of apomorphine. These data indicate that apomorphine activity at
      TAAR1 contributes to some behavioral manifestations, particularly climbing, in
      rodents following high doses of this drug. The contribution of TAAR1 to
      apomorphine-induced climbing in rodents should be considered when apomorphine is
      used as a screening tool in the search for potential antipsychotics. 

PMID- 24925024
TI  - Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation
      signaling in human TCRVgamma9+ gammadelta T lymphocytes.
AB  - Human gammadelta cells expressing TCRVgamma9 are T lymphocytes with great
      potential for cancer immunotherapy and unconventional pattern of antigen
      specificity. These HLA-unrestricted lymphocytes are specifically reactive to non
      peptide metabolites (phosphoantigens) and to the butyrophilin 3A (BTN3A/CD277)
      protein. Whether recognition of such highly different structures trigger the same
      activation signaling pathway remains unclear, however. Here we combined
      fluorescent cell barcoding and phosphoflow analysis of TCRVgamma9(+) T
      lymphocytes to compare simultaneously the level of several signaling
      phosphoproteins after activation by phosphoantigen (BrHPP) or by anti-BTN3A
      (monoclonal antibody 20.1). This approach shows that the same pathways involving
      ZAP70, PLCgamma2, Akt, NFkappaB p65, MAPK p38 and Erk1, were induced by either of
      these stimuli. These data strongly suggest the TCRVgamma9(+) T lymphocytes detect
      phosphoantigens and butyrophilin A3 by the same recognition process. 

PMID- 24925025
TI  - Prevalence and factors associated with wound colonization by Staphylococcus spp.
      and Staphylococcus aureus in hospitalized patients in inland northeastern Brazil:
      a cross-sectional study.
AB  - BACKGROUND: Infections by Staphylococcus spp. are often associated with wounds,
      especially in hospitalized patients. Wounds may be the source of bacteria causing
      cross-contamination, and are a risk factor for methicillin-resistant
      Staphylococcus aureus (MRSA) infection. The aim of this study was to investigate
      the prevalence of wound colonization by Staphylococcus spp., especially S. aureus
      and MRSA, in hospitalized patients, and to identify the factors associated with
      such colonization. METHODS: This cross-sectional study enrolled patients with
      wounds who were hospitalized in a remote and underdeveloped inland region of
      northeastern Brazil with extreme poverty. Samples were collected using sterile
      swabs with 0.85% saline solution, and coagulase-negative Staphylococcus spp., S.
      aureus, and MRSA were identified using standard laboratory procedures. Data
      regarding the sociodemographic characteristics, antibiotic use, and comorbidities
      of the patients were collected using the medical records and a questionnaire.
      RESULTS: A total of 125 wounds were analyzed. The patients had a mean age of
      63.88 years and a mean 3.84 years of school education. Eighty-one wounds (64.80%)
      were colonized by Staphylococcus spp. Twenty-five wounds (20%) were colonized by
      S. aureus, 32% of which were colonized by MRSA. Wound colonization by
      Staphylococcus spp. was associated with pneumonia or other respiratory disease (p
      = 0.03). Wound colonization by S. aureus was associated with nasal colonization
      by S. aureus (p < 0.001), fewer days of prior antibiotic use (p = 0.04),
      admission to a medical ward (p = 0.02), and age >65 years (p = 0.05). Among
      patients with wound colonization by MRSA, 37.50% had a history of prior
      antibiotic use, 75% had two or more comorbidities, 25% had cancer or diabetes,
      50% had cardiovascular disease, and 50% died. CONCLUSIONS: Wounds can be the
      source of Staphylococcus spp. infection, and high proportions of wounds are
      colonized by S. aureus and MRSA. Nasal colonization by S. aureus may be a source
      for wound colonization by S. aureus, illustrating the importance of preventing
      cross-contamination in hospital environments, especially among elderly patients.
      Wounds should be carefully managed to prevent microbial spread, thereby assisting
      patient recovery and reducing healthcare costs.

PMID- 24925026
TI  - Williams-beuren syndrome is a genetic disorder associated with impaired glucose
      tolerance and diabetes in childhood and adolescence: new insights from a
      longitudinal study.
AB  - BACKGROUND: In adults with Williams-Beuren syndrome (WBS), a common endocrine
      abnormality is type 2 diabetes mellitus (T2DM) or impaired glucose tolerance
      (IGT). However, few and sporadic data are available in children, adolescents, and
      young adults with WBS. AIM: To evaluate the frequency of IGT and T2DM in a cohort
      of children and young patients with WBS. PATIENTS AND METHODS: We longitudinally
      evaluated 27 patients (9 males and 18 females, median age at study onset 13.6
      years) with WBS. The median follow-up was 3.6 years. Variables of insulin
      resistance and beta-cell function were evaluated in all subjects using an oral
      glucose tolerance test. The homeostasis model assessment (HOMA) of insulin
      resistance and the Matsuda index of insulin sensitivity were calculated. The
      study of the GCK and HNF1Alpha genes was performed in patients with glucose
      metabolism abnormalities. 45 age- and sex-matched healthy subjects and 51 age-,
      sex- and BMI-matched subjects were recruited as two control groups. RESULTS:
      Considering nutritional status, 7 (25.9%) patients were obese, 9 (33.3%)
      overweight, and 11 (40.8%) normal-weight. One (3.1%) patient had acanthosis
      nigricans. IGT was diagnosed in 7 (25.9%) WBS patients and T2DM in 3 (11.1%).
      Considering all WBS patients, the median value of HOMA was 5.23 (range 2.93
      14.89; insulin 24.73 +/- 14.67 MUU/ml; glucose 104.98 +/- 16.06 mg/dl).
      Considering BMI values, HOMA was 11.00 (range 6.53-12.56), 5.64 (range 3.54
      7.95), and 4.54 (range 3.21-5.43), and insulin was 34.53 +/- 6.84, 22.76 +/-
      8.91, and 19.47 +/- 6.01 MUU/ml in obese, overweight, and normal-weight WBS
      patients, respectively. Comparing the results with the two control groups, WBS
      patients showed higher insulin values than healthy controls (p < 0.001), but
      similar values as the BMI-matched control group (p = n.s.). However, WBS patients
      showed significantly higher values of glycemia (healthy control group, p < 0.001;
      BMI-matched control group, p < 0.05) and HOMA (healthy control group, p < 0.001;
      BMI-matched control group, p < 0.05) than the two control groups. Finally, among
      WBS patients there was a higher number of subjects with IGT and T2DM than among
      healthy controls (p < 0.0001) and the BMI-matched control group (p = 0.0002).
      CONCLUSION: Our data strongly suggest that IGT and T2DM may be frequently
      discovered in children, adolescents, and young adults with WBS. WBS should be
      included among the genetic syndromes associated with T2DM. Further studies are
      necessary to evaluate the etiopathogenesis of this aspect.

PMID- 24925027
TI  - Exosome-derived miRNAs and ovarian carcinoma progression.
AB  - The objective of this study was to analyze the expression, biological role and
      clinical relevance of exosomal microRNAs (miRNAs) from ovarian carcinoma (OC)
      effusion supernatants. Exosomal miRNA expression profiling was performed using
      miRNA Taqman arrays. Selected miRNAs were validated using quantitative PCR in 86
      OC effusion supernatants. The role of exosomal miRNA in this cancer was further
      studied using in vitro and in vivo models. miRNA profiling identified 99 miRNAs
      with high expression levels in exosomes from OC effusion supernatants.
      Quantitative PCR validation of 11 miRNAs showed significant associations with
      effusion site (peritoneum versus pleura) and International Federation of
      Gynecology and Obstetrics stage. In univariate survival analysis, high levels of
      miRNAs 21, 23b and 29a were associated with poor progression-free survival (P =
      0.01, P = 0.015 and P = 0.009, respectively), whereas high expression of miRNA 21
      correlated with poor overall survival (P = 0.017). The latter association was
      retained in Cox multivariate analysis (P = 0.001). Exposure of LP9 mesothelial
      cells and ES2 OC cells to OC effusion-derived exosomes inhibited tumor spheroid
      expansion and reduced mesothelial clearance area. Treatment of severe combined
      immunodeficiency mice with exosomes from OC effusions prior to injection of tumor
      cells was associated with larger tumor load, more infiltrative tumors and shorter
      survival. Patient-derived OC effusion exosomes contain multiple miRNAs, of which
      some may have clinical relevance. In experimental models, OC exosomes affect both
      tumor cells and cells in the tumor microenvironment and induce more aggressive
      disease. Collectively, these data demonstrate the central role of miRNAs and
      their content in the biology of this cancer. 

PMID- 24925028
TI  - MicroRNA-200b targets protein kinase Calpha and suppresses triple-negative breast
      cancer metastasis.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer
      with poor prognosis and lacks effective targeted therapies. The microRNA-200 (miR
      200) family is found to inhibit or promote breast cancer metastasis; however, the
      underlying mechanism is not well understood. This study was performed to
      investigate the effect and mechanism of miR-200b on TNBC metastasis and identify
      targets for developing more efficient treatment for TNBC. We found that miR-200
      family expression levels are significantly lower in highly migratory TNBC cells
      and metastatic TNBC tumors than other types of breast cancer cells and tumors.
      Ectopically expressing a single member (miR-200b) of the miR-200 family
      drastically reduces TNBC cell migration and inhibits tumor metastasis in an
      orthotopic mouse mammary xenograft tumor model. We identified protein kinase
      Calpha (PKCalpha) as a new direct target of miR-200b and found that PKCalpha
      protein levels are inversely correlated with miR-200b levels in 12 kinds of
      breast cancer cells. Inhibiting PKCalpha activity or knocking down PKCalpha
      levels significantly reduces TNBC cell migration. In contrast, forced expression
      of PKCalpha impairs the inhibitory effect of miR-200b on cell migration and tumor
      metastasis. Further mechanistic studies revealed that PKCalpha downregulation by
      miR-200b results in a significant decrease of Rac1 activation in TNBC cells.
      These results show that loss of miR-200b expression plays a crucial role in TNBC
      aggressiveness and that miR-200b suppresses TNBC cell migration and tumor
      metastasis by targeting PKCalpha. Our findings suggest that miR-200b and PKCalpha
      may serve as promising therapeutic targets for metastatic TNBC. 

PMID- 24925030
TI  - [Obituary - Bruce E. Del Mar (1913-2014)].

PMID- 24925029
TI  - Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis.
AB  - N-alpha-Acetyltransferase 10 protein (Naa10p, also called arrest-defective 1),
      the catalytic subunit of N-acetyltransferase A, is a critical regulator of cell
      death and proliferation. Naa10p is also shown to regulate cancer metastasis by
      inhibiting cell motility; however, its role in cancer metastasis is not fully
      understood. In this study, we found that high expression of Naa10p is positively
      correlated with the survival of patients with breast cancer, whereas negatively
      correlated with lymph node metastasis. Naa10p inhibits breast cancer cell
      migration and invasion in vitro and decreases the xenograft growth and metastasis
      in nude mice. Microarray screening revealed that Naa10p downregulates inhibitors
      of differentiation 1 (ID1) expression. Naa10p binds to signal transducer and
      activator of transcription 5a (STAT5a) and decreases STAT5a-stimulated ID1
      expression in an acetyltransferase-independent manner. Moreover, Naa10p
      antagonizes Janus kinase 2-STAT5a signaling by lowering p65-activated interleukin
      1beta expression. Our results demonstrate a novel mechanism through which Naa10p
      inhibits the metastasis of breast cancer cells by targeting STAT5a. 

PMID- 24925031
TI  - Pancreatic cancer stem cells: association with cell surface markers, prognosis,
      resistance, metastasis and treatment.
AB  - In this review, we will discuss the recent advances in understanding the
      pancreatic cancer stem cells. Identification and characterization of pancreatic
      cancer stem cells may aid our ability to improve diagnosis and treatment of
      pancreatic cancer. Novel approaches are necessary for the earlier diagnosis of
      pancreatic cancer as well as improved treatment to prevent distal metastasis. Key
      markers for the identification of pancreatic cancer stem cells include CD133,
      ALDH, side population cells and the triplet combination CD44+ CD24+ESA+. The
      roles of these proteins as markers for stemness in pancreatic cancer as well as
      recent studies with the c-Met proto-oncogene will be discussed. The ability of
      these markers to predict survival of pancreatic cancer patients is being examined
      clinically. Stemness and resistance to chemotherapy and radiotherapy may be
      linked. Expression of some of these markers may be associated with distant
      metastasis. Treatment of pancreatic cancer patients by targeting the pancreatic
      cancer stem cells holds promise. 

PMID- 24925033
TI  - Validation of a student satisfaction survey for clinical education placements in
      dietetics.
AB  - BACKGROUND: Finite or shrinking health resources, coupled with increasing
      clinical student placement demand, raise many challenges, including potential
      impacts on placement quality. One method of measuring quality is through the use
      of validated tools and systematic evaluation; however, no validated dietetic
      student satisfaction surveys could be identified. METHOD: An electronic student
      survey assessing clinical placement satisfaction was developed, using survey
      items from the literature and questions clinical educators considered pertinent.
      Pilot testing ensured understandability and content validity. The confidential,
      electronic student clinical placement satisfaction survey was provided to health
      services statewide and completed by students following their final placement
      assessment (160 responses from 290 placements). Forty-seven statements were
      scored on a 5-point Likert scale (strongly disagree to strongly agree), with
      overall placement satisfaction assessed on a 10-point scale (very poor to
      exceptional). RESULTS: No metropolitan, regional, or remote differences were
      evident with regard to sample representativeness (n=160). Two factors
      encompassing 28 items (related to supervisors and clinicial educators) accounted
      for 78% of the variance. Good internal consistency was evident (Cronbach's alpha
      0.98). CONCLUSION: This study establishes the construct validity of an instrument
      by which the satisfaction of dietetic students with their clinical placement can
      now be evaluated. Knowing students' satisfaction with clinical placements is but
      one potential outcome measure of a quality educational program, but it is
      essential for enhancing the educational experience.

PMID- 24925032
TI  - Porphyromonas gingivalis fimbriae dampen P2X7-dependent interleukin-1beta
      secretion.
AB  - Porphyromonas gingivalis is a major contributor to the pathogenesis of
      periodontitis, an infection-driven inflammatory disease that leads to bone
      destruction. This pathogen stimulates pro-interleukin (IL)-1beta synthesis but
      not mature IL-1beta secretion, unless the P2X7 receptor is activated by
      extracellular ATP (eATP). Here, we investigated the role of P. gingivalis
      fimbriae in eATP-induced IL-1beta release. Bone marrow-derived macrophages
      (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with P.
      gingivalis (381) or isogenic fimbria-deficient (DPG3) strain with or without
      subsequent eATP stimulation. DPG3 induced higher IL-1beta secretion after eATP
      stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This
      mechanism was dependent on K(+) efflux and Ca(2+)-independent phospholipase A2
      activity. Accordingly, non-fimbriated P. gingivalis failed to inhibit apoptosis
      via the eATP/P2X7 pathway. Furthermore, P. gingivalis-driven stimulation of IL
      1beta was Toll-like receptor 2 and MyD88 dependent, and not associated with
      fimbria expression. Fimbria-dependent down-modulation of IL-1beta was selective,
      as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal
      microscopy demonstrated the presence of discrete P2X7 expression in the absence
      of P. gingivalis stimulation, which was enhanced by 381-stimulated cells.
      Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor
      expression with a marked focus formation. Collectively, these data demonstrate
      that eATP-induced IL-1beta secretion is impaired by P. gingivalis fimbriae in a
      P2X7-dependent manner.

PMID- 24925034
TI  - Burnout among physical therapist assistant program directors: a nationwide survey
      and analysis.
AB  - PURPOSE: The purpose of this study was to assess burnout in directors of physical
      therapist assistant (PTA) programs and to analyze the relationship between
      individual and institutional variables and burnout. METHODS: Surveys were
      completed by 120 directors from accredited PTA programs. The surveys consisted of
      demographic information and the Maslach Burnout Inventory-Educators Survey (MBI
      ES). The MBI-ES assesses burnout in the areas of emotional exhaustion,
      depersonalization, and personal accomplishment. RESULTS: PTA program directors
      showed moderate levels of emotional exhaustion, low levels of depersonalization,
      and high levels of personal accomplishment. Gender, the number of faculty in a
      department, and length of academic contract had no correlation with participant
      burnout levels. Significantly lower levels of emotional exhaustion were found in
      participants who were in their current position for more than 11 years and those
      who planned to remain in their current position or within higher education for at
      least 5 additional years. A significant negative correlation was found between
      participant age and depersonalization. DISCUSSION: PTA program directors and
      their institutions should develop strategies to minimize the effects of burnout
      in younger program directors and those in the early years of their position.

PMID- 24925035
TI  - International recruitment of allied health professionals to the United States:
      piecing together the picture with imperfect data.
AB  - BACKGROUND: Research on the international recruitment of health professionals to
      the U.S. has focused almost exclusively on physicians and nurses; we are aware of
      no research on the migration of allied health professionals. OBJECTIVE: We
      examined the strengths and weaknesses of various public and private data sources
      on foreign-educated allied health professions in the U.S. and patched together a
      picture of these migrants. We focus on pharmacists, physical therapists (PTs),
      occupational therapists (OTs), speech language pathologists (SLPs), and medical
      and clinical laboratory technicians (lab techs). FINDINGS: Based on the American
      Community Survey, we found that 12% of PTs, 12% of lab techs, 8% of pharmacists,
      4% of OTs, and 3% of SLPs are foreign-born and entered the U.S. at age 21 or
      older. Among foreign-born PTs, about half remain as non-citizens, suggesting the
      highest proportion of recent arrivals among the five professions. CONCLUSIONS: As
      Congress debates comprehensive immigration reform, one of the much need changes
      to the system is better immigration data, disaggregated by occupation.

PMID- 24925036
TI  - Predicting discharge placement and health care needs after lumbar spine
      laminectomy.
AB  - OBJECTIVE: To explore factors associated with discharge placement (DP) and need
      for skilled assistance after patients are discharged from hospital following
      lumbar laminectomy. METHODS: A retrospective analysis of 339 patients who
      underwent lumbar laminectomy was conducted. We used multivariable logistic
      regression analysis to identify significant covariates and to construct two
      regression models: a primary model to predict DP, home vs inpatient
      rehabilitation/skilled nursing facility (IR/SNF), and a secondary model to
      predict the need for skilled assistance once patients are discharged to home.
      RESULTS: The sample included 48.7% females, 68.2% married, 56.3% independent in
      daily activities, and 85.2% discharged to home. Subjects were a mean 56.06 +/-
      12.75 years old and had a BMI of 31.35 +/- 6.2. Of those discharged to home,
      17.7% needed skilled assistance. Patients stayed 4.41 +/- 3.55 days in the
      hospital and walked 203.38 +/- 144.87 ft during hospital stay. Age, distance
      walked during hospital stay, and length of hospital stay (LOS) were significant
      positive predictors for discharge to home vs IR/SNF, whereas single living
      status, diminished prior level of function, and longer LOS were predictors of
      need for skilled assistance after discharge to home. CONCLUSION: Age, mobility,
      marital status, prior level of function, and LOS are key variables in determining
      healthcare needs following lumbar laminectomy.

PMID- 24925037
TI  - Research priorities for the therapy professions in Northern Ireland and the
      Republic of Ireland: a comparison of findings from a Delphi consultation.
AB  - BACKGROUND: Allied health professions constitute a large and growing proportion
      of the healthcare workforce. As a collective they are involved in complex care
      interventions often within multidisciplinary teams and increasingly in community
      settings. Even though reliable information is lacking, some professions do appear
      to have developed an active research culture, whereas others are more limited in
      terms of research. PURPOSE: This paper reports on the comparative findings of two
      Delphi studies, one in Northern Ireland and one in the Republic of Ireland,
      undertaken between 2008 and 2011. The aim of both studies was to identify
      research priorities for six of the therapy professions. METHOD: A classic Delphi
      approach was used involving expert panels from the therapy disciplines, service
      users, and key stakeholders. RESULTS: Both studies provided rich sources of data.
      Areas of commonality included the evaluation of practice generally and specific
      interventions common to each of the professions. More effective service
      management and health promotion research were also identified as important in
      both countries. CONCLUSIONS: As the global number of allied health professionals
      increases, along with the need for them to support their practice with sound
      evidence, the findings from this paper have international implications.

PMID- 24925038
TI  - A roadmap for change: charting the course of the development of a new, advanced
      role for radiation therapists.
AB  - A new model of care has been piloted in Ontario that expands the role of
      radiation therapists to improve access and treatment quality for patients
      requiring radiation therapy. The advanced practice Clinical Specialist Radiation
      Therapist (CSRT) role was created to redistribute activities amongst healthcare
      team members, allowing each to work to the full scope of practice, thereby better
      streamlining services, addressing systematic pressures in the existing model of
      care, and increasing patients' access to treatment. This paper provides an
      overview of the approaches used to develop and implement an advanced practice
      (AP) role, and it offers guidance on the use of an evidence-based approach to the
      evaluation of such positions. This article also utilizes the experience and
      knowledge developed during the CSRT projects to provide a framework for
      organizations embarking on similar AP implementation initiatives.

PMID- 24925039
TI  - The HITECH Act and electronic health records' limitation in coordinating care for
      children with complex chronic conditions.
AB  - While the HITECH Act was implemented to promote the use of electronic health
      records to improve the quality and coordination of healthcare, the limitations
      established to the setting of the hospital or physician's office affect the care
      coordination for those who utilize many health-related services outside these
      settings, including children with complex and chronic conditions. Incentive-based
      support or nationally supported electronic health record systems for allied and
      other healthcare professionals are necessary to see the full impact that
      electronic health records can have on care coordination for individuals who
      utilize many skilled healthcare services that are not associated with a hospital
      or physician's office. 

PMID- 24925040
TI  - Physical therapy as an adjunct treatment for people living with HIV/AIDS: an
      allied health perspective.
AB  - With the increased life expectancy for people living with HIV/AIDS (PLWHA) has
      come chronic HIV-related impairments, many of which can be successfully treated
      by physical therapy (PT). The purpose of this study is to determine common HIV
      related impairments that merit PT, HIV providers' PT referral patterns and
      patients' barriers to care. 57 surveys were distributed to HIV providers in
      Atlanta, Georgia. Results showed that providers typically referred to PT for
      musculoskeletal conditions, neurological conditions and pain control. Financial
      issues and lack of insurance were the most common barriers to PT care. This study
      concluded that there is a need for PT services amongst PLWHA and that financial
      limitations are a significant treatment barrier for PLWHA.

PMID- 24925041
TI  - Challenges ahead of emergency medical technician graduates in the workplace in
      Iran: a qualitative study.
AB  - OBJECTIVE: Emergency medical technicians (EMTs) in Iran enter the workplace after
      a short academic education. Their workplace has high emotional fluctuations and
      imposes high pressure. The aim of this study was to assess the challenges faced
      by EMT graduates in Iran. DESIGN: This applied study was conducted using
      qualitative content analysis. Twelve paramedics and graduates with 2 to 3 years
      of service were interviewed and their responses were analyzed by content
      analysis. RESULTS: Findings were presented in five themes: organizational
      pressure, educational style, professional communication, emotional load, and
      misunderstanding of others. CONCLUSION: Several problems confront EMTs in Iran.
      Educators and educational planners in this discipline could help resolve these
      problems by revising problematic points in the education and management of EMT
      graduates and by revising educational methods and human resource management to
      provide better services and save lives.

PMID- 24925042
TI  - Creating an IPE infusion plan: from foundation to implementation.
AB  - Today's health care system has embraced the model of collaborative
      interprofessional efforts among health care professionals to achieve desired
      patient health outcomes. The Academy can offer the foundational experiences
      needed to support and develop interprofessional patient-centered plans of care
      for health professional students. This paper explores one institution's approach
      to the creation of an infusion plan which the authors have termed a "structured
      immersion approach" (SIA) to interprofessional education (IPE). The SIA supports
      "Core Signature IPE" experiences within existing silo-based curriculums that
      allow for interprofessional education experiences and the appreciation of the
      importance of interprofessional practice in today's health care.

PMID- 24925043
TI  - Student perspectives on interprofessional education and experiences.
AB  - PURPOSE: The purpose of this mixed-method study was to explore students'
      attitudes, knowledge, experience, and receptiveness to interprofessional
      education (IPE) in the health sciences. METHODS: An embedded mixed-method design
      was used whereby 29 students from 5 health sciences schools (Law, Medicine,
      Nursing, Pharmacy, Social Work) were administered The Readiness for
      Interprofessional Learning Scale (RIPLS) and participated in semi-structured
      interviews. RESULTS: Quantitative results indicated that there was no significant
      difference regarding readiness for interprofessional learning among the different
      academic disciplines. Qualitative interviews identified that students were
      exposed to two types of interprofessional learning experiences: curricular IPE
      and clinical interprofessional training (IPT). The majority of interprofessional
      experiences occurred through internships, student activities, and community
      service opportunities, not in the classroom. The study findings also uncovered
      lost opportunities for IPE, characteristics of successful interprofessional
      learning, and students' personal and organizational barriers to IPE. CONCLUSION:
      Results have implications for creating and implementing IPE and IPT experiences
      for students in the health sciences. Specifically, it is important to bring these
      students together as a collaborative team, both within the classroom and within a
      clinical setting. This will require a unique type of curriculum and team of
      instructors.

PMID- 24925044
TI  - Early severe HIV disease precedes early antiretroviral therapy in infants: Are we
      too late?
AB  - OBJECTIVE: To describe the degree of HIV disease progression in infants
      initiating antiretroviral therapy (ART) by three months of age in a programmatic
      setting in South Africa. DESIGN: This was a programmatic cohort study. METHODS:
      Electronic and manual data extraction from databases and antiretroviral registers
      in 20 public clinics in Cape Town and electronic data extraction from a large ART
      service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of
      all infants initiated on ART by three months of age between June 2007 and
      September 2010 were extracted. Demographics, immunological and clinical stage at
      ART initiation were analyzed descriptively by chi-square, two-sample t-test and
      Kaplan-Meier methods. RESULTS: A total of 403 records were identified: 88 in Cape
      Town and 315 in Soweto. Median age at ART initiation was 8.4 [interquartile range
      (IQR): 7.2-9.7] weeks. At ART initiation, 250 infants (62%) had advanced HIV
      disease (CD4% <25% or absolute CD4<1500 cells/mm(3) or WHO clinical Stage 3 or
      4). Median age at ART initiation by site was 10.3 (IQR: 8.2-11.9) weeks in Cape
      Town and 8.6 (IQR: 7.7-10.0) weeks in Soweto infants (p<0.0001). In Cape Town, 73
      infants (83%) had advanced HIV disease at ART initiation, compared to 177 infants
      (56%) in Soweto (p<0.0001). On logistic regression, each month increase in age at
      ART initiation lowered the odds of initiating ART in an optimal state (OR: 0.56,
      CI: 0.36-0.94) and increased the odds of advanced HIV disease at ART initiation
      (OR: 1.69, CI: 1.05-2.71). CONCLUSIONS: ART initiation by three months of age may
      not adequately prevent disease progression. New emphasis on early diagnosis and
      rapid initiation of ART in the first weeks of life are essential to further
      reduce infant mortality.

PMID- 24925045
TI  - Applications of biosynthesized metallic nanoparticles - a review.
AB  - We present a comprehensive review of the applications of biosynthesized metallic
      nanoparticles (NPs). The biosynthesis of metallic NPs is the subject of a number
      of recent reviews, which focus on the various "bottom-up" biofabrication methods
      and characterization of the final products. Numerous applications exploit the
      advantages of biosynthesis over chemical or physical NP syntheses, including
      lower capital and operating expenses, reduced environmental impacts, and superior
      biocompatibility and stability of the NP products. The key applications reviewed
      here include biomedical applications, especially antimicrobial applications, but
      also imaging applications, catalytic applications such as reduction of
      environmental contaminants, and electrochemical applications including sensing.
      The discussion of each application is augmented with a critical review of the
      potential for continued development. 

PMID- 24925046
TI  - Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal
      delivery: cancer therapy by circumventing the skin barrier.
AB  - The transdermal administration of chemotherapeutic agents is a persistent
      challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is
      attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION).
      The covalent modification of the SPION results in EPI-SPION, a potential drug
      delivery vector that uses magnetism for the targeted transdermal chemotherapy of
      skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic
      responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They
      feature specific pH-sensitive drug release, targeting the acidic microenvironment
      typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies
      using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that
      SPION have good biocompatibility. After conjugation with EPI, the nanoparticles
      can inhibit WM266 cell proliferation; its inhibitory effect on tumor
      proliferation is determined to be dose-dependent. In vitro transdermal studies
      demonstrate that the EPI-SPION composites can penetrate deep inside the skin
      driven by an external magnetic field. The magnetic-field-assisted SPION
      transdermal vector can circumvent the stratum corneum via follicular pathways.
      The study indicates the potential of a SPION-based vector for feasible
      transdermal therapy of skin cancer. 

PMID- 24925047
TI  - The emerging use of Twitter by urological journals.
AB  - OBJECTIVE: To assess the emerging use of Twitter by urological journals. METHODS:
      A search of the Journal of Citation Reports 2012 was performed to identify
      urological journals. These journals were then searched on Twitter.com. Each
      journal website was accessed for links to social media (SoMe). The number of
      'tweets', followers and age of profile was determined. To evaluate the content,
      over a 6-month period (November 2013 to April 2014), all tweets were scrutinised
      on the journals Twitter profiles. To assess SoMe influence, the Klout score of
      each journal was also calculated. RESULTS: In all, 33 urological journals were
      identified. Eight (24.2%) had Twitter profiles. The mean (range) number of tweets
      and followers was 557 (19-1809) and 1845 (82-3692), respectively. The mean
      (range) age of the twitter profiles was 952 (314-1758) days with an average 0.88
      tweets/day. A Twitter profile was associated with a higher mean impact factor of
      the journal (mean [sd] 3.588 [3.05] vs 1.78 [0.99], P = 0.013). Over a 6-month
      period, November 2013 to April 2014, the median (range) number of tweets per
      profile was 82 (2-415) and the median (range) number of articles linked to tweets
      was 73 (0-336). Of these 710 articles, 152 were Level 1 evidence-based articles,
      101 Level 2, 278 Level 3 and 179 Level 4. The median (range) Klout score was 47
      (19-58). The Klout scores of major journals did not exactly mirror their impact
      factors. CONCLUSION: SoMe is increasingly becoming an adjunct to traditional
      teaching methods, due to its convenient and user-friendly platform. Recently,
      many of the leading urological journals have used Twitter to highlight
      significant articles of interest to readers.

PMID- 24925048
TI  - Treating the untreatable patient: current options for the management of treatment
      resistant neovascular age-related macular degeneration.
AB  - Anti-vascular endothelial growth factor (anti-VEGF) agents represent the current
      standard of care for neovascular age-related macular degeneration (nAMD).
      Although effective in a majority of cases, a significant proportion of patients
      have persisting retinal exudation despite regular anti-VEGF therapy. This
      exudation is considered to produce poorer visual outcomes in these patients. Some
      of these patients may have misdiagnosed nAMD variants such as polypoidal
      choroidal vasculopathy; however, the majority of these eyes have what has been
      termed treatment-resistant nAMD. Currently, the best way to care for these
      patients is uncertain. Here, we review the evidence for different approaches to
      the management of treatment-resistant nAMD, including high-dose anti-VEGF
      therapy, combination regimes and switching of anti-VEGF agents, and discuss
      possible therapeutic approaches for patients with treatment-resistant nAMD.

PMID- 24925049
TI  - Body image and depressive symptoms in patients with head and neck cancer: an
      important relationship.
AB  - PURPOSE: The purpose of this study is to examine the relationship between body
      image and depressive symptoms in patients who have been treated for head and neck
      cancer. METHODS: This is a prospective, longitudinal analysis. Body image and
      depressive symptoms were measured in patients diagnosed with head and neck cancer
      at baseline, end of treatment, 6 weeks post-treatment, and 12 weeks post
      treatment. Body image was measured using the Body Image Quality of Life
      Inventory, and depressive symptoms were measured using the Center for
      Epidemiological Studies Depression Scale. RESULTS: Forty-three individuals
      diagnosed with head and neck cancer participated in this study. The majority of
      participants were male, Caucasian, and married or living with a partner.
      Participants ranged from age 32 to 78 years (M = 57.8 years, SD = 10.5 years). At
      12 weeks post-treatment, body image scores were statistically significantly
      higher than they were at the end of treatment (p = 0.016) and 6 weeks post
      treatment (p = 0.032). Statistically significant increases in levels of
      depressive symptoms were observed at the end of treatment (p < 0.001) and 6 weeks
      post-treatment (p = 0.036) with a return to baseline by the 12-week post
      treatment assessment (p = 0.115). Body image and depressive symptoms were
      statistically significantly associated at the end of treatment, 6 weeks post
      treatment, and 12 weeks post-treatment (r s -0.32 to -0.56, p < 0.05).
      CONCLUSIONS: This study supports early assessment of body image in patients with
      head and neck cancer. Additionally, the association between poorer body image and
      increased depressive symptoms is key in understanding the symptom clusters that
      patients with head and neck cancer experience.

PMID- 24925050
TI  - White matter segmentation based on a skeletonized atlas: effects on diffusion
      tensor imaging studies of regions of interest.
AB  - PURPOSE: To compare the influence of conventional and skeletonized atlas-based
      white matter (WM) segmentation on diffusion tensor imaging (DTI) region-of
      interest (ROI) investigations. MATERIALS AND METHODS: A conventional WM atlas was
      skeletonized by thinning the corresponding fractional anisotropy (FA) map and
      labels. The conventional and skeletonized versions of the atlas were used for WM
      segmentation. The percentage of non-WM voxels assigned to WM labels, as well as
      statistical summaries of tensor-derived quantities, were compared between
      segmentation approaches. The ability to detect small differences in diffusion
      properties across groups of subjects was also compared between segmentation
      approaches. RESULTS: Skeletonized segmentation resulted in significantly lower
      non-WM percentage (P < 0.05), higher mean FA and lower trace (P < 0.05) in most
      WM labels, and mainly lower standard deviation of FA and trace in labels
      neighboring the ventricles. In terms of maximizing the ability to detect
      intergroup DTI differences, skeletonized segmentation was superior in the corpus
      callosum, but the optimal approach varied for other WM labels. CONCLUSION:
      Conventional and skeletonized atlas-based segmentation probe different portions
      of brain tissue and lead to different statistical summaries of diffusion
      characteristics in WM labels. Careful selection of segmentation approach is
      required for DTI investigations of WM ROIs.

PMID- 24925051
TI  - Congestive hepatic fibrosis score: a novel histologic assessment of clinical
      severity.
AB  - Chronic right heart failure predisposes to hepatic passive congestion and
      centrizonal necrosis that may lead to hepatic fibrosis (cardiac sclerosis).
      Although there have been several studies on the histologic features of congestive
      hepatopathy, there is no available grading system. In this study we developed a
      novel grading system for congestive hepatic fibrosis. Liver biopsies were
      examined in patients with chronic heart failure of various etiologies including
      congenital heart disease, idiopathic cardiomyopathy, ischemic heart disease, and
      valvular heart disease. The cases with available echocardiography and/or right
      heart catheterization were included. Cases with other types of underlying chronic
      liver diseases, alcoholic liver disease, significant steatosis (>20%), malignant
      neoplasm, and acute heart failure or shock were excluded. After exclusion, 42
      cases were included in the study. We herein proposed a novel congestive hepatic
      fibrosis score and correlated it with the right heart structure and function
      obtained by echocardiography and/or right heart catheterization. Our results
      showed that congestive hepatic fibrosis score is well correlated with the right
      atrial pressure (P for trend <0.001). The presence of portal fibrosis (congestive
      hepatic fibrosis scores 2 and 3) is associated with significantly higher right
      atrial pressure than those with no fibrosis (P<0.001) or with centrizonal
      fibrosis only (P=0.02). Congestive hepatic fibrosis score is also significantly
      associated with increasing severity of right atrial dilatation (P=0.03) and right
      ventricular dilatation (P=0.02), indicators for chronic volume and/or pressure
      overload. Other histopathologic features include sinusoidal dilatation and
      centrizonal hepatocyte atrophy. In summary, although sinusoidal dilatation and
      centrizonal fibrosis are the hallmarks of hepatic passive congestion, the
      presence of portal fibrosis is suggestive of more advanced disease, as it
      correlates with more severe impairment of right heart function, regardless of the
      etiologies of right heart failure. Congestive hepatic fibrosis score is a useful
      indicator of clinical severity. 

PMID- 24925052
TI  - Comparison of different prostatic markers in lymph node and distant metastases of
      prostate cancer.
AB  - Prostate cancer is mostly diagnosed at an early stage; however, some tumors are
      diagnosed in a metastatic stage as cancer of unknown primary origin. In order to
      allow specific treatment in the case of prostate cancer presenting as cancer of
      unknown primary origin, it is important to determine the tumor origin. Prostate
      specific antigen is used as a diagnostic marker for prostate cancer but the
      expression declines with progression to castration-resistant prostate cancer. Aim
      of this study was to identify the most informative marker constellation, which is
      able to detect metastatic prostate cancer at high sensitivity. The widely used
      prostate cancer markers such as prostate-specific antigen, prostate-specific acid
      phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and
      ETS-related gene were investigated for their sensitivity to detect prostatic
      origin of metastases. Expression of prostate-specific antigen, prostate-specific
      acid phosphatase, androgen receptor, prostate-specific membrane antigen,
      prostein, and ETS-related gene was determined on archived tissue specimens
      consisting of benign prostatic tissue (n=9), primary prostate cancer (n=79),
      lymph node metastases (n=58), and distant metastases (n=39) using
      immunohistochemistry. The staining intensity was categorized as negative (0),
      weak (1), moderate (2), and strong (3). All markers except ETS-related gene were
      able to detect at least 70% of lymph node metastases and distant metastases, with
      prostate-specific antigen, androgen receptor, and prostate-specific membrane
      antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A
      further increase of the sensitivity up to 98% and 100% could be achieved by the
      combination of prostate-specific antigen, prostate-specific membrane antigen, or
      androgen receptor for lymph node metastases and for distant metastases,
      respectively. The same sensitivity could be reached by combining prostate
      specific membrane antigen and prostein. Our data show that a combined staining of
      at least two prostate markers should be utilized to identify metastases as
      originating from prostate cancer. 

PMID- 24925053
TI  - Long non-coding RNAs in cancer invasion and metastasis.
AB  - Recent large-scale transcriptome analyses have revealed that the human genome
      contains more than just protein-coding genes. Indeed, a large number of
      transcripts, including long non-coding RNAs (lncRNAs), lack protein-coding
      capacity, and increasing evidence suggests that lncRNAs could have a critical
      role in the regulation of diverse cellular processes, such as stem cell
      pluripotency, development, cell growth and apoptosis, and cancer invasion and/or
      metastasis. Furthermore, the aberrant expression of several lncRNAs is closely
      linked to cancer invasion and/or metastasis. Although the underlying molecular
      mechanisms by which lncRNAs regulate cancer invasion and/or metastasis are not
      clearly understood, recent studies have revealed that aberrant lncRNAs expression
      affects the progression of cancer. In this review, we highlight recent findings
      regarding the roles of lncRNAs in cancer invasion and/or metastasis. 

PMID- 24925054
TI  - Primary sources of pelvic serous cancer in patients with endometrial
      intraepithelial carcinoma.
AB  - Serous endometrial intraepithelial carcinoma is often associated with
      extrauterine disease. It is currently unclear where does the extrauterine disease
      come from. This study addressed this issue. A total of 135 samples from 21 serous
      endometrial intraepithelial carcinoma patients were studied. Cellular lineage
      relationships between intrauterine and extrauterine serous carcinomas were
      determined by TP53-mutation analysis and correlated to the clinicopathologic
      features. There were three conditions contributing the extrauterine disease:
      metastasis from serous endometrial intraepithelial carcinoma (n=10) showed
      identical TP53 mutation between intrauterine lesions and extrauterine disease,
      cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed
      cellular origin cases (n=6) with both identical and discordant mutation status.
      Patients with extrauterine disease from serous endometrial intraepithelial
      carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine
      sites and without finding of serous tubal intraepithelial carcinoma, while
      extrauterine disease with adnexal or tubal origin commonly had larger tumor
      masses in extrauterine sites including ovary and omentum and serous tubal
      intraepithelial carcinoma. The majority of extrauterine diseases associated with
      serous endometrial intraepithelial carcinoma are metastasized from the
      endometrium. Serous endometrial intraepithelial carcinoma is frequently
      associated with serous cancers of adnexal or tubal origin, indicating that
      endometrial and adnexal or tubal serous cancers may share similar etiologies.
      TP53-mutation analysis provides a strong linkage for cellular lineage analysis.
      Tumor size in extrauterine disease and presence of serous tubal intraepithelial
      carcinoma or not are useful clinicopathologic features to determine primary
      cancer site, which helps in clinical management.

PMID- 24925055
TI  - mTORC1 and FGFR1 signaling in fibrolamellar hepatocellular carcinoma.
AB  - Fibrolamellar hepatocellular carcinoma, or fibrolamellar carcinoma, is a rare
      form of primary liver cancer that afflicts healthy young men and women without
      underlying liver disease. There are currently no effective treatments for
      fibrolamellar carcinoma other than resection or transplantation. In this study,
      we sought evidence of mechanistic target of rapamycin complex 1 (mTORC1)
      activation in fibrolamellar carcinoma, based on anecdotal reports of tumor
      response to rapamycin analogs. Using a tissue microarray of 89 primary liver
      tumors, including a subset of 10 fibrolamellar carcinomas, we assessed the
      expression of phosphorylated S6 ribosomal protein (P-S6), a downstream target of
      mTORC1, along with fibroblast growth factor receptor 1 (FGFR1). These results
      were extended and confirmed using an additional 13 fibrolamellar carcinomas,
      whose medical records were reviewed. In contrast to weak staining in normal
      livers, all fibrolamellar carcinomas on the tissue microarray showed strong
      immunostaining for FGFR1 and P-S6, whereas only 13% of non-fibrolamellar
      hepatocellular carcinomas had concurrent activation of FGFR1 and mTORC1 signaling
      (P<0.05). When individual samples were stratified according to staining intensity
      (scale 0-4), the average score in fibrolamellar carcinomas was 2.46 for FGFR1 and
      3.77 for P-S6, compared with 0 and 0, respectively, in non-tumor liver.
      Immunoblot analyses of fibrolamellar carcinomas revealed high mTORC1 activities
      relative to AKT activities accompanied by reduced TSC2 expression, which was not
      observed in non-fibrolamellar hepatocellular carcinomas. Our findings provide
      evidence for mTORC1 activation and FGFR1 overexpression in human fibrolamellar
      carcinoma, and support the use of FGFR1 inhibitors and rapamycin analogs in the
      treatment of patients with unresectable fibrolamellar carcinoma. 

PMID- 24925056
TI  - Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with
      aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid
      fibro-osseous lesions.
AB  - To evaluate the diagnostic value of MDM2 status in craniofacial fibro-osseous
      lesions, we investigated MDM2 expression by immunohistochemistry and analyzed
      MDM2 amplification by qPCR in 30 cases of ossifying fibroma (including 13 cases
      of the juvenile variant) and 17 cases of fibrous dysplasia. Two cases of uncommon
      extragnathic psammomatoid fibrous dysplasia and a mixed control group of 15 cases
      of low-grade osteosarcoma and 15 cases of well-differentiated/dedifferentiated
      liposarcoma were included. MDM2 amplification was found in 33% of ossifying
      fibromas (peak of 69% for the juvenile variant) and in 12% of fibrous dysplasia,
      in none of which was MDM2 overexpressed. All control cases exhibited MDM2
      amplification and overexpression. To investigate possible polysomy of chromosome
      12, we studied RASAL1 amplification, a gene telomeric to MDM2 on the long arm of
      chromosome 12. RASAL1 amplification was reported in all benign fibro-osseous
      lesions exhibiting MDM2 amplification but not in controls. Simultaneous
      amplification of these two genes was significantly higher in juvenile ossifying
      fibromas compared with fibrous dysplasia (P=0.004), non-juvenile ossifying
      fibromas (P=0.001), and all other benign craniofacial fibro-osseous lesions
      combined (P=0.0001). Of the nine cases of juvenile ossifying fibroma exhibiting
      amplification, three were locally invasive and four were recurrent, suggesting
      aggressive disease. The two cases of extragnathic psammomatoid fibrous dysplasia
      also showed MDM2 and RASAL1 amplification with no MDM2 overexpression. This large
      chromosome 12 rearrangement, spanning MDM2 and RASAL1, is the first recurrent
      molecular abnormality to be reported in juvenile ossifying fibroma. It may
      represent both a molecular diagnostic marker and a characteristic of more
      aggressive forms with a higher risk of recurrence. Finally, the presence of this
      rearrangement in extragnathic psammomatoid fibro-osseous lesions mimicking
      ossifying fibromas might reflect a common molecular pathway in their pathogenesis
      and calls into question the classification of such lesions within fibrous
      dysplasia. 

PMID- 24925057
TI  - Distinct WNT/beta-catenin signaling activation in the serrated neoplasia pathway
      and the adenoma-carcinoma sequence of the colorectum.
AB  - Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the
      serrated neoplasia pathway leading to colorectal cancer development. The
      conventional adenoma-carcinoma sequence is associated with activation of the WNT
      signaling pathway, although its role in serrated lesions is still controversial.
      To clarify differences in WNT signaling activation in association with MLH1
      methylation or BRAF/KRAS mutations between serrated and conventional routes, we
      performed beta-catenin immunostaining, methylation-specific PCR for MLH1 and WNT
      signaling associated genes such as AXIN2, APC, and MCC and secreted frizzled
      related proteins (SFRPs), and direct sequencing of BRAF/KRAS in 27 SSA/Ps, 14
      SSA/Ps with high-grade dysplasia and 9 SSA/Ps with submucosal carcinoma, as well
      as 19 conventional adenomas, 26 adenomas with high-grade dysplasia and 25
      adenomas with submucosal carcinoma. Nuclear beta-catenin labelings were
      significantly lower in the serrated series than in their adenoma counterparts,
      and a significant increment in those labelings was found from SSA/Ps to those
      with high-grade dysplasia or submucosal carcinoma. The frequency of MLH1 and
      SFRP4 methylation was significantly higher in SSA/P series, as compared with
      corresponding adenoma series. AXIN2 and MCC were more frequently methylated in
      SSA/Ps with high-grade dysplasia and those with submucosal carcinoma than in
      adenoma counterparts. Stepwise increment of AXIN2 and MCC methylation was
      identified from SSA/Ps through those with high-grade dysplasia to those with
      submucosal carcinoma. A significant correlation was seen between nuclear beta
      catenin expression and methylation of AXIN2 or MCC in the SSA/P series. BRAF
      mutation was more frequent, whereas KRAS mutation was less frequent in the SSA/P
      series as compared with the adenoma series. There was an inverse association of
      BRAF mutation with AXIN2 methylation in SSA/P series. In conclusion, WNT/beta
      catenin signal activation mediated by the methylation of SFRP4, MCC, and AXIN2
      may make different contributions to colorectal neoplasia between the serrated and
      conventional routes. 

PMID- 24925059
TI  - Michael Lappert (1928-2014).

PMID- 24925060
TI  - Tibial and fibular mid-shaft bone traits in young and older sprinters and non
      athletic men.
AB  - High impact loading is known to prevent some of the age-related bone loss but its
      effects on the density distribution of cortical bone are relatively unknown. This
      study examined the effects of age and habitual sprinting on tibial and fibular
      mid-shaft bone traits (structural, cortical radial and polar bone mineral density
      distributions). Data from 67 habitual male sprinters aged 19-39 and 65-84 years,
      and 60 non-athletic men (referents) aged 21-39 and 65-80 years are reported.
      Tibial and fibular mid-shaft bone traits (strength strain index SSI, cortical
      density CoD, and polar and radial cortical density distributions) were assessed
      with peripheral quantitative computed tomography. Analysis of covariance (ANCOVA)
      adjusted for height and body mass indicated that the sprinters had 21 % greater
      tibial SSI (P < 0.001) compared to the referents, with no group * age-group
      interaction (P = 0.54). At the fibula no group difference or group * age-group
      interaction was identified (P = 0.12-0.81). For tibial radial density
      distribution ANCOVA indicated no group * radial division (P = 0.50) or group *
      age-group * division interaction (P = 0.63), whereas an age * radial division
      interaction was observed (P < 0.001). For polar density distribution, no age
      group * polar sector (P = 0.21), group * polar sector (P = 0.46), or group * age
      group * polar sector interactions were detected (P = 0.15). Habitual sprint
      training appears to maintain tibial bone strength, but not radial cortical
      density distribution into older age. Fibular bone strength appeared unaffected by
      habitual sprinting. 

PMID- 24925058
TI  - Etiologic field effect: reappraisal of the field effect concept in cancer
      predisposition and progression.
AB  - The term 'field effect' (also known as field defect, field cancerization, or
      field carcinogenesis) has been used to describe a field of cellular and molecular
      alteration, which predisposes to the development of neoplasms within that
      territory. We explore an expanded, integrative concept, 'etiologic field effect',
      which asserts that various etiologic factors (the exposome including dietary,
      lifestyle, environmental, microbial, hormonal, and genetic factors) and their
      interactions (the interactome) contribute to a tissue microenvironmental milieu
      that constitutes a 'field of susceptibility' to neoplasia initiation, evolution,
      and progression. Importantly, etiological fields predate the acquisition of
      molecular aberrations commonly considered to indicate presence of filed effect.
      Inspired by molecular pathological epidemiology (MPE) research, which examines
      the influence of etiologic factors on cellular and molecular alterations during
      disease course, an etiologically focused approach to field effect can: (1)
      broaden the horizons of our inquiry into cancer susceptibility and progression at
      molecular, cellular, and environmental levels, during all stages of tumor
      evolution; (2) embrace host-environment-tumor interactions (including gene
      environment interactions) occurring in the tumor microenvironment; and, (3) help
      explain intriguing observations, such as shared molecular features between
      bilateral primary breast carcinomas, and between synchronous colorectal cancers,
      where similar molecular changes are absent from intervening normal colon. MPE
      research has identified a number of endogenous and environmental exposures which
      can influence not only molecular signatures in the genome, epigenome,
      transcriptome, proteome, metabolome and interactome, but also host immunity and
      tumor behavior. We anticipate that future technological advances will allow the
      development of in vivo biosensors capable of detecting and quantifying 'etiologic
      field effect' as abnormal network pathology patterns of cellular and
      microenvironmental responses to endogenous and exogenous exposures. Through an
      'etiologic field effect' paradigm, and holistic systems pathology (systems
      biology) approaches to cancer biology, we can improve personalized prevention and
      treatment strategies for precision medicine. 

PMID- 24925061
TI  - Repression of phosphoinositide-dependent protein kinase 1 expression by
      ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer
      cell growth.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors gamma (PPARgamma) ligands
      have been shown to inhibit the growth of non-small cell lung cancer (NSCLC)
      cells. However, the mechanisms underlying this effect remain incompletely
      elucidated. METHODS: Cell proliferation and apoptosis were measured by cell
      viability, MTT and caspase3/7 activity assays. Phosphorylation/protein expression
      and gene silence/overexpression of AMPKalpha, phosphoinositide-dependent protein
      kinase 1 (PDK1), Egr-1 and PPARgamma were performed by Western blot and
      siRNA/transfection assays. Dual-Luciferase Reporter Kit was used to measure the
      PPAR response elements (PPRE) reporter and PDK1 promoter activities, and ChIP
      assay was used to detect the Egr-1 protein binding to the DNA site in the PDK1
      gene promoter. RESULTS: We found that ciglitazone, one synthetic PPARgamma
      ligand, inhibited growth and induced apoptosis of NSCLC cells through decreased
      expression of PDK1, which was not blocked by GW9662 (a specific PPARgamma
      antagonist). Overexpression of PDK1 overcame the effect of ciglitazone on cell
      growth and caspase 3/7 activity. Ciglitazone increased the phosphorylation of
      AMPKalpha and c-Jun N-terminal kinase (JNK), and the inhibitor of AMPK (compound
      C), but not JNK (SP600125), reversed the effect of ciglitazone on PDK1 protein
      expression. Ciglitazone reduced PDK1 gene promoter activity, which was not
      observed in cells exposed to compound C, but not silenced of PPARgamma siRNA.
      Combination of ciglitazone and metformin further reduced PDK1 expression and
      promoter activity. Furthermore, we showed that ciglitazone induced the protein
      expression of Egr-1, which was not observed in cells silencing of AMPKalpha.
      Moreover, silencing of Egr-1 abrogated the effect of ciglitazone on PDK1 promoter
      activity and cell growth. On the contrary, overexpression of Egr-1 enhanced the
      effect of ciglitazone on PDK1 gene promoter activity. ChIP assays demonstrated
      that ciglitazone induced Egr-1 protein bind to the specific DNA site in the PDK1
      gene promoter. CONCLUSION: Collectively, our results demonstrate that ciglitazone
      inhibits PDK1 expression through AMPKalpha-mediated induction of Egr-1 and Egr-1
      binding to the specific DNA site in the PDK1 gene promoter, which is independent
      of PPARgamma. Activation of AMPKalpha by metformin enhances the effect of
      ciglitazone. In turn, this leads to inhibition of NSCLC cell proliferation.

PMID- 24925062
TI  - Ag@4ATP-coated liposomes: SERS traceable delivery vehicles for living cells.
AB  - A liposome-Ag nanohybrid has been demonstrated as a SERS traceable intracellular
      drug nanocarrier. Liposomes have been introduced for their special qualities in
      drug delivery systems. In essence, 4-aminothiophenol (4ATP) tagged Ag
      nanoparticles (Ag@4ATP) were adsorbed onto the surfaces of liposomes via
      electrostatic interactions, in which 4ATP was used as a SERS reporter. In such a
      nanohybrid, the locations of the carrier can be tracked by SERS signals while
      those of the drugs can be monitored through their fluorescence, allowing the
      simultaneous investigation of the intracellular distribution of both the carriers
      and the drugs. Our experimental results suggest that the reported liposomal
      system has substantial potential for intracellular drug delivery. 

PMID- 24925064
TI  - Invited commentary: multilevel analysis of individual heterogeneity-a fundamental
      critique of the current probabilistic risk factor epidemiology.
AB  - In this issue of the Journal, Dundas et al. (Am J Epidemiol. 2014;180(2):197-207)
      apply a hitherto infrequent multilevel analytical approach: multiple membership
      multiple classification (MMMC) models. Specifically, by adopting a life-course
      approach, they use a multilevel regression with individuals cross-classified in
      different contexts (i.e., families, early schools, and neighborhoods) to
      investigate self-reported health and mental health in adulthood. They provide
      observational evidence suggesting the relevance of the early family environment
      for launching public health interventions in childhood in order to improve health
      in adulthood. In their analyses, the authors distinguish between specific
      contextual measures (i.e., the association between particular contextual
      characteristics and individual health) and general contextual measures (i.e., the
      share of the total interindividual heterogeneity in health that appears at each
      level). By doing so, they implicitly question the traditional probabilistic risk
      factor epidemiology including classical "neighborhood effects" studies. In fact,
      those studies use simple hierarchical structures and disregard the analysis of
      general contextual measures. The innovative MMMC approach properly responds to
      the call for a multilevel eco-epidemiology against a widespread probabilistic
      risk factors epidemiology. The risk factors epidemiology is not only reduced to
      individual-level analyses, but it also embraces many current "multilevel
      analyses" that are exclusively focused on analyzing contextual risk factors. 

PMID- 24925065
TI  - Early-life school, neighborhood, and family influences on adult health: a
      multilevel cross-classified analysis of the Aberdeen children of the 1950s study.
AB  - Lifetime exposures to adverse social environments influence adult health, as do
      exposures in early life. It is usual to examine the influences of school on
      teenage health and of adult area of residence on adult health. We examined the
      combined long-term association of the school attended, as well as the area of
      residence in childhood, with adult health. A total of 6,285 children from
      Aberdeen, Scotland, who were aged 5-12 years in 1962, were followed up at a mean
      age of 47 years in 2001. Cross-classified multilevel logistic regression was used
      to estimate the associations of family, school, and area of residence with self
      reported adult health and mental health, adjusting for childhood family-, school
      , and neighborhood-level factors, as well as current adult occupational position.
      Low early-life social position (as determined by the father's occupational level)
      was associated with poor adult self-rated health but not poor mental health.
      There were small contextual associations between childhood school environment
      (median odds ratio = 1.08) and neighborhood environment (median odds ratio =
      1.05) and adult self-rated health. The share of the total variance in health at
      the family level was 10.1% compared with 89.6% at the individual level. Both
      socioeconomic context and composition in early life appear to have an influence
      on adult health, even after adjustment for current occupational position. 

PMID- 24925066
TI  - Tackling student binge drinking: Pairing incongruent messages and measures
      reduces alcohol consumption.
AB  - OBJECTIVES: Excessive alcohol consumption is a persistent problem in Northern
      European cultures. Across a 2-week period, we tested the effect of varying
      message frames, message types, and response measures, in reducing alcohol
      consumption. DESIGN: Three hundred and twenty-three respondents were allocated to
      a 2 (message frame: gain vs. loss) * 2 (message type: health vs. social) * 2
      (response type: engaging vs. refraining) mixed design. METHOD: Binge drinking and
      units consumed were measured at Time 1 and Time 2 (2 weeks later). Participants
      read (following Time 1) a gain- or loss-framed message on binging emphasizing
      either social or health consequences and answered engaging in or refraining from
      drinking attitude measures. RESULTS: No main effects were identified. The key
      finding was that gain-framed messages, when used in conjunction with engage
      response measures (an incongruous pairing), were highly effective in reducing
      alcohol consumption 2 weeks later compared with the other message frame/response
      measure combinations. CONCLUSIONS: We suggest that for prevention behaviours,
      gain-framed messages, when paired with engage response measures, initiate an
      inconsistency resolution process. Together, our findings emphasize the importance
      of message frame and response type when seeking to reduce alcohol consumption
      using persuasive health messages.

PMID- 24925067
TI  - Culture, context and the implementation challenge to achieve a better birth
      experience.

PMID- 24925068
TI  - Pathologic fracture of the distal radius in a 25-year-old patient with a large
      unicameral bone cyst.
AB  - BACKGROUND: Distal radius fractures (DRF) are often referred to as osteoporosis
      indicator fractures as their incidence increases from age 45. In the group of
      young adults, distal radius fractures normally result from high-energy trauma.
      Wrist fractures in young patients without adequate trauma thus raise suspicion of
      a pathologic fracture. In this report we present the case of a fractured
      unicameral bone cyst (UBC) at the distal radius in a young adult.To the author's
      best knowledge, this is the first detailed report in an UBC at the distal radius
      causing a pathologic DRF in an adult patient. CASE PRESENTATION: A 25-year-old
      otherwise healthy male presented to our Emergency Department after a simple fall
      on his right outstretched hand. Extended diagnostics revealed a pathologic,
      dorsally displaced, intra-articular distal radius fracture secondary to a
      unicameral bone cyst occupying almost the whole metaphysis of the distal radius.
      To stabilize the fracture, a combined dorsal and volar approach was used for open
      reduction and internal fixation. A tissue specimen for histopathological
      examination was gathered and the lesion was filled with an autologous bone graft
      harvested from the ipsilateral femur using a reamer-irrigator-aspirator (RIA)
      system. Following one revision surgery due to an intra-articular step-off, the
      patient recovered without further complications. CONCLUSIONS: Pathologic
      fractures in young patients caused by unicameral bone cysts require extended
      diagnostics and adequate treatment. A single step surgical treatment is
      reasonable if fracture and bone cyst are treated appropriately. Arthroscopically
      assisted fracture repair may be considered in intra-articular fractures or
      whenever co-pathologies of the carpus are suspected.

PMID- 24925069
TI  - Structure-based studies on the metal binding of two-metal-dependent sugar
      isomerases.
AB  - Two-metal-dependent sugar isomerases are important in the synthesis of rare
      sugars. Many of their properties, specifically their metal dependency, have not
      been sufficiently explored. Here we used X-ray crystallography, site-directed
      mutagenesis, isothermal titration calorimetry and electron paramagnetic resonance
      spectroscopy to investigate the molecular determinants of the metal-binding
      affinity of l-rhamnose isomerase, a two-Mn(2+) -dependent isomerase from Bacillus
      halodurans (BHRI). The crystal structure of BHRI confirmed the presence of two
      metal ion-binding sites: a structural metal ion-binding site for substrate
      binding, and a catalytic metal ion-binding site that catalyzes a hydride shift.
      One conserved amino acid, W38, in wild-type BHRI was identified as a critical
      residue for structural Mn(2+) binding and thus the catalytic efficiency of BHRI.
      This function of W38 was explored by replacing it with other amino acids.
      Substitution by Phe, His, Lys, Ile or Ala caused complete loss of catalytic
      activity. The role of W38 was further examined by analyzing the crystal structure
      of wild-type BHRI and two inactive mutants of BHRI (W38F and W38A) in complex
      with Mn(2+) . A structural comparison of the mutants and the wild-type revealed
      differences in their coordination of Mn(2+) , including changes in metal-ligand
      bond length and affinity for Mn(2+) . The role of W38 was further confirmed in
      another two-metal-dependent enzyme: xylose isomerase from Bacillus licheniformis.
      These data suggest that W38 stabilizes protein-metal complexes and in turn
      assists ligand binding during catalysis in two-metal-dependent isomerases.
      STRUCTURED DIGITAL ABSTRACT: BHRI and BHRI bind by x-ray crystallography (View
      interaction).

PMID- 24925070
TI  - Acute effects of low-level laser therapy on physiologic and electromyographic
      responses to the cardiopulmonary exercise testing in healthy untrained adults.
AB  - Despite the positive effects of low-level laser therapy (LLLT) on muscle fatigue
      before exercises using a single muscle group, the acute effects of LLLT on
      performance in cardiopulmonary exercise testing (CPET) are poorly understood. We
      aimed to assess the acute effects of LLLT on physiologic and electromyographic
      responses to the CPET in healthy adults. A randomized, double-blind, placebo
      controlled crossover trial was performed with 18 untrained participants (nine
      males, 22 +/- 2 years). We applied LLLT or placebo on quadriceps and
      gastrocnemius 10 min before two rapidly incremental CPETs randomly performed in
      alternate days on a cycle ergometer. Participants received LLLT using a
      multidiode cluster, 20 s/site (850 nm, 100 mW/diode, 14 J/site). Physiological
      responses to the CPET were continuously monitored using a gas analyzer. The
      electromyographic fatigue threshold (EMGth) was assessed through surface
      electrodes on vastus lateralis. The root mean square (RMS) was plotted every 5 s
      against the exercise intensity, and its breakpoint values throughout the CPET was
      identified as EMGth. Compared to placebo, the LLLT significantly increased peak
      O2 uptake (V'O2 33 +/- 10 vs. 31 +/- 9 mL/min/kg). We observed a shallower slope
      of the Deltaheart rate/DeltaV'O2 during the CPET after LLLT compared to placebo,
      i.e., increased cardiovascular efficiency (56 +/- 24 vs. 66 +/- 30 bpm/L/min).
      There were no LLLT-related changes in EMGth. The LLLT acutely increases exercise
      performance in healthy untrained adults probably due to increased O2 extraction
      by peripheral muscles without causing a significant impact on muscle fatigue.

PMID- 24925071
TI  - UPLC-MS/MS determination of voriconazole in human plasma and its application to a
      pharmacokinetic study.
AB  - A sensitive and rapid ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS) method was developed to determine voriconazole in human
      plasma. Sample preparation was accomplished through a simple one-step protein
      precipitation with methanol. Chromatographic separation was carried out on an
      Acquity UPLC BEH C18 column using an isocratic mobile phase system composed of
      acetonitrile and water containing 1% formic acid (45:55, v/v) at a flow rate of
      0.50 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass
      spectrometer coupled with an electrospray ionization source in the positive ion
      mode. The multiple reaction monitoring transitions of m/z 351.0 -> 281.5 and m/z
      237.1 -> 194.2 were used to quantify voriconazole and carbamazepine (internal
      standard), respectively. The linearity of this method was found to be within the
      concentration range of 2.0-1000 ng/mL with a lower limit of quantification of 2.0
      ng/mL. Only 1.0 min was needed for an analytical run. This fully validated method
      was successfully applied to the pharmacokinetic study after oral administration
      of 200 mg voriconazole to 20 Chinese healthy male volunteers.

PMID- 24925072
TI  - Acute heat-evoked temperature sensation is impaired but not abolished in mice
      lacking TRPV1 and TRPV3 channels.
AB  - The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion
      channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and
      injury-evoked heat temperature sensation. ThermoTRPV channels are activated by
      partially overlapping temperatures ranging from warm to supra-threshold noxious
      heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be
      activated by warm as well as noxious heat temperatures. Loss-of-function studies
      in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature
      sensation is not completely abolished suggesting functional redundancies among
      these two channels and highlighting the need of a detailed analysis of
      TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close
      proximity of the loci expressing the two channels. Here we describe the
      generation of a novel mouse model in which trpv1 and trpv3 genes have been
      inactivated using bacterial artificial chromosome (BAC)-based homologous
      recombination in embryonic stem cells. In these mice, using classical
      thermosensory tests such hot plate, tail flick and the thermotaxis gradient
      paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat
      temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a
      well-defined window of acute moderate heat temperature. Using the dynamic hot
      plate assay, we unravel an intriguing and unexpected pronounced escape behavior
      in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in
      agreement with the temperature activation overlap between TRPV1 and TRPV3
      channels, our data provide in vivo evidence of a cooperative role between skin
      derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of
      moderate and noxious heat temperature sensation and suggest that other mechanisms
      are required for heat temperature sensation. 

PMID- 24925073
TI  - Reliability and validity of the Balance Evaluation Systems Test (BESTest) in
      people with subacute stroke.
AB  - BACKGROUND: The Balance Evaluation Systems Test (BESTest) is a new clinical
      balance assessment tool, but it has never been validated in patients with
      subacute stroke. OBJECTIVE: The purpose of this study was to examine the
      reliability and validity of the BESTest in patients with subacute stroke. DESIGN:
      This was an observational reliability and validity study. METHODS: Twelve
      patients participated in the interrater and intrarater reliability study.
      Convergent validity was investigated in 70 patients using the Berg Balance Scale
      (BBS), Postural Assessment Scale for Stroke (PASS), Community Balance and
      Mobility Scale (CB&M), and Mini-BESTest. The receiver operating characteristic
      curve was used to calculate the sensitivity, specificity, and accuracy of the
      BESTest, Mini-BESTest, and BBS in classifying participants into low functional
      ability (LFA) and high functional ability (HFA) groups based on Fugl-Meyer
      Assessment motor subscale scores. RESULTS: The BESTest showed excellent
      intrarater reliability and interrater reliability (intraclass correlation
      coefficient=.99) and was highly correlated with the BBS (Spearman r=.96), PASS
      (r=.96), CB&M (r=.91), and Mini-BESTest (r=.96), indicating excellent convergent
      validity. No floor or ceiling effects were observed with the BESTest. In
      contrast, the Mini-BESTest and CB&M had a floor effect in the LFA group, and the
      BBS and PASS demonstrated responsive ceiling effects in the HFA group. In
      addition, the BESTest showed high accuracy as the BBS and Mini-BESTest in
      separating participants into HFA and LFA groups. LIMITATION: Whether the results
      are generalizable to patients with chronic stroke is unknown. CONCLUSION: The
      BESTest is reliable, valid, sensitive, and specific in assessing balance in
      people with subacute stroke across all levels of functional disability.

PMID- 24925074
TI  - Pain interference is associated with psychological concerns related to falls in
      community-dwelling older adults: multisite observational study.
AB  - BACKGROUND: Pain interference and psychological concerns related to falls (PCRF)
      are pervasive phenomena among community-dwelling older adults, yet their
      association remains elusive. OBJECTIVE: The purpose of this study was to
      establish whether pain interference is associated with PCRF in community-dwelling
      older adults. DESIGN: This was a multisite cross-sectional study. METHOD: Two
      hundred ninety-five community-dwelling older adults (mean age=77.5 years, SD=8.1;
      66.4% female) participated in the study. All participants completed the Brief
      Pain Inventory (BPI) interference subscale, Short Falls Efficacy Scale
      International (FES-I), Activities-specific Balance Confidence Scale (ABC),
      modified version of the Survey of Activities and Fear of Falling in Elderly Scale
      (mSAFFE), and Consequences of Falling Scale (CoF). Hierarchical multiple
      regression analysis were conducted. In the first step of the study,
      sociodemographic and known risk factors for psychological concerns related to
      falls were inserted into the model, followed by the BPI interference subscale
      score in the second step. RESULTS: One hundred sixty-nine participants (57.3%)
      reported some pain interference. The BPI interference subscale was highly
      correlated with all PCRF (r>.5, P<.0001). After the adjustment for established
      risk factors, the BPI interference subscale significantly increased the variance
      in the Short FES-I (R2 change=13.2%), ABC (R2 change=4.7%), mSAFFE (R2
      change=5.0%), and CoF (R2 change=10.0%). Pain interference was a significant and
      independent predictor in the final model for the Short FES-1 (beta=0.455,
      P<.001), ABC (beta=-0.265, P<.001), mSAFFE (beta=0.276, P<.001), and CoF
      (beta=0.390, P<.001). LIMITATIONS: The study was cross-sectional. CONCLUSIONS:
      Pain interference is an important contributing factor in each of the
      psychological concerns related to falls. Pain interference had the strongest
      impact on reducing falls efficacy and increasing older adults' concerns about the
      consequences of falling.

PMID- 24925075
TI  - Perspectives on the evolution of mobile (mHealth) technologies and application to
      rehabilitation.
AB  - Individuals with chronic conditions and disabilities who are vulnerable to
      secondary complications often require complex habilitative and rehabilitative
      services to prevent and treat these complications. This perspective article
      reviews the evolution of mHealth technologies and presents insights as to how
      this evolution informed our development of a novel mHealth system, iMHere
      (interactive mobile health and rehabilitation), and other technologies, including
      those used by the Veterans Administration. This article will explain the novel
      applications of mHealth for rehabilitation and specifically physical therapy.
      Perspectives on the roles of rehabilitation professionals in the delivery of
      health care using mHealth systems are included. Challenges to mHealth, including
      regulatory and funding issues, are discussed. This article also describes how
      mHealth can be used to improve patient satisfaction and delivery of care and to
      promote health and wellness. 

PMID- 24925076
TI  - Influences of wheelchair-related efficacy on life-space mobility in adults who
      use a wheelchair and live in the community.
AB  - BACKGROUND: Self-efficacy has important implications for health and functioning
      in people with limited mobility. However, the influence of self-efficacy on
      mobility in adults who use wheelchairs has yet to be investigated. OBJECTIVE: The
      study objective was to: (1) estimate the direct association between wheelchair
      use self-efficacy and life-space mobility and (2) investigate an indirect effect
      through wheelchair skills. DESIGN: This was a cross-sectional study. METHODS:
      Participants (N=124) were adults who use a wheelchair, live in the community, and
      were 50 years of age and older (X=59.67, range=50-84), with at least 6 months of
      experience with manual wheelchair use; 60% were men. The 20-item Life-Space
      Assessment, the 65-item Wheelchair Use Confidence Scale, and the 32-item
      Wheelchair Skills Test-Questionnaire were used to measure life-space mobility,
      self-efficacy, and wheelchair skills, respectively. RESULTS: Self-efficacy had a
      statistically significant association with life-space mobility (nonstandardized
      regression coefficient=0.23, 95% confidence interval=0.07, 0.39) after
      controlling for sex, number of comorbidities, geographic location, and assistance
      with using a wheelchair. This model accounted for 37.1% of the life-space
      mobility variance, and the unique contribution of self-efficacy was 3.5%. The
      indirect effect through wheelchair skills was also statistically significant
      (point estimate=0.21, 95% bootstrapped confidence interval=0.05, 0.43) and
      accounted for 91.3% of the direct effect of self-efficacy on life-space mobility.
      This model accounted for 39.2% of the life-space mobility variance. LIMITATIONS:
      Causality could not be established because of the study design. The self-report
      nature of data from volunteers may be influenced by recall bias, social
      desirability, or both. CONCLUSIONS: Wheelchair use self-efficacy had both direct
      and indirect associations with life-space mobility after controlling for
      confounding variables. Interventions targeted toward improving self-efficacy may
      lead to improvements in life-space mobility.

PMID- 24925077
TI  - Extended cervico-thoracic metastasectomy for testicular non-seminomatous germ
      cell tumour masses through an inverse T and combined collar incision.
AB  - Non-seminomatous germ cell tumours (NSGCT) are the most common malignancy from
      testicular origin in young males. They are characterized by early formation of
      metastases along retroperitoneal and subsequent mediastinal lymph node stations.
      Following cisplatin-based induction chemotherapy, residual tumour masses should
      be removed surgically, although this implies the need for extended procedures.
      Such an approach can result in cure rates of over 70%. Herein, we report 2 cases
      of maximally extended surgery for metastatic malignant germ cell tumour of the
      testis. In both patients, diagnostic work-up revealed a NSGCT with
      retroperitoneal, mediastinal and cervical lymph node metastases. Multimodal
      protocols including induction chemotherapy and surgical removal of all primary
      and secondary tumour masses with curative intent were applied. An 'inverse T'
      incision in combination with a collar incision was chosen to approach the
      excessive supra-diaphragmatic tumour spread. This large-scaled surgical access
      offered an excellent exposure and allowed complete resection of all cervical and
      thoracic metastases in both patients. Abdominal tumour masses were resected
      through a standard median laparotomy. These 2 cases illustrate that complete
      tumour resection is feasible even in stages of NSGCT with generalized lymphatic
      spread. Metastasectomy should be offered to NSGCT patients despite the necessity
      of extended surgical approaches. 

PMID- 24925078
TI  - A ring on the heart.

PMID- 24925079
TI  - Is body dysmorphic disorder associated with abnormal bodily self-awareness? A
      study using the rubber hand illusion.
AB  - Evidence from past research suggests that behaviours and characteristics related
      to body dissatisfaction may be associated with greater instability of perceptual
      body image, possibly due to problems in the integration of body-related
      multisensory information. We investigated whether people with body dysmorphic
      disorder (BDD), a condition characterised by body image disturbances,
      demonstrated enhanced susceptibility to the rubber hand illusion (RHI), which
      arises as a result of multisensory integration processes when a rubber hand and
      the participant's hidden real hand are stimulated in synchrony. Overall,
      differences in RHI experience between the BDD group and healthy and schizophrenia
      control groups (n = 17 in each) were not significant. RHI strength, however, was
      positively associated with body dissatisfaction and related tendencies. For the
      healthy control group, proprioceptive drift towards the rubber hand was observed
      following synchronous but not asynchronous stimulation, a typical pattern when
      inducing the RHI. Similar drifts in proprioceptive awareness occurred for the BDD
      group irrespective of whether stimulation was synchronous or not. These results
      are discussed in terms of possible abnormalities in visual processing and
      multisensory integration among people with BDD. 

PMID- 24925080
TI  - A synthetic manassantin a derivative inhibits hypoxia-inducible factor 1 and
      tumor growth.
AB  - The dineolignan manassantin A from Saururaceae was recently identified as a
      hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect
      has not been explored. We synthesized a series of manassantin A derivatives, and
      found that replacing the central tetrahydrofuran moiety with a cyclopentane ring
      yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet
      decreased stereochemically complexity amenable to a simplified synthesis scheme.
      LXY6006 inhibited HIF-1alpha nuclear accumulation induced by hypoxia, and
      inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration
      of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors
      implanted in nude mice. These results indicate that LXY6006 represents a novel
      class of agents targeting a broad range of human cancers. 

PMID- 24925081
TI  - Perfectionistic Tendencies in Insomnia Patients' Behavior During Psychometric
      Testing.
AB  - According to self-report questionnaire studies, insomnia patients differ from
      healthy controls with respect to several personality traits. The current study
      aimed at exploring how these personality traits may translate into behavior.
      Insomnia patients' behavior during psychometric testing (n = 163) was
      investigated in comparison to healthy controls (n = 81), patients with other
      sleep disorders (n = 80), and patients with obsessive-compulsive disorder (n =
      36). In line with our hypotheses, insomnia patients made more additional comments
      than healthy controls and more corrections than patients with other sleep
      disorders during sleep-related questionnaire completion. Furthermore, insomnia
      patients calculated the sum score of a depression questionnaire more frequently
      than both healthy controls and patients with other sleep disorders. These
      findings further support the assumption of an altered personality profile in
      patients with primary insomnia. Future work should aim to elucidate what
      personality factors these novel behavioral markers may reflect. 

PMID- 24925082
TI  - Screen failure data in clinical trials: Are screening logs worth it?
AB  - BACKGROUND: Clinical trials frequently spend considerable effort to collect data
      on patients who were assessed for eligibility but not enrolled. The Consolidated
      Standards of Reporting Trials (CONSORT) guidelines' recommended flow diagram for
      randomized clinical trials reinforces the belief that the collection of screening
      data is a necessary and worthwhile endeavor. The rationale for collecting
      screening data includes scientific, trial management, and ethno-socio-cultural
      reasons. PURPOSE: We posit that the cost of collecting screening data is not
      justified, in part due to inability to centrally monitor and verify the screening
      data in the same manner as other clinical trial data. METHODS: To illustrate the
      effort and site-to-site variability, we analyzed the screening data from a
      multicenter, randomized clinical trial of patients with transient ischemic attack
      or minor ischemic stroke (Platelet-Oriented Inhibition in New Transient Ischemic
      Attack and Minor Ischemic Stroke (POINT)). RESULTS: Data were collected on over
      27,000 patients screened across 172 enrolling sites, 95% of whom were not
      enrolled. Although the rate of return of screen failure logs was high overall
      (95%), there were a considerable number of logs that were returned with 'no data
      to report' (23%), often due to administrative reasons rather than no patients
      screened. CONCLUSION: In spite of attempts to standardize the collection of
      screening data, due to differences in site processes, multicenter clinical trials
      face challenges in collecting those data completely and uniformly. The efforts
      required to centrally collect high-quality data on an extensive number of
      screened patients may outweigh the scientific value of the data. Moreover, the
      lack of a standardized definition of 'screened' and the challenges of collecting
      meaningful characteristics for patients who have not signed consent limits the
      ability to compare across studies and to assess generalizability and selection
      bias as intended.

PMID- 24925083
TI  - Inference about the expected performance of a data-driven dynamic treatment
      regime.
AB  - BACKGROUND: A dynamic treatment regime (DTR) comprises a sequence of decision
      rules, one per stage of intervention, that recommends how to individualize
      treatment to patients based on evolving treatment and covariate history. These
      regimes are useful for managing chronic disorders, and fit into the larger
      paradigm of personalized medicine. The Value of a DTR is the expected outcome
      when the DTR is used to assign treatments to a population of interest. PURPOSE:
      The Value of a data-driven DTR, estimated using data from a Sequential Multiple
      Assignment Randomized Trial, is both a data-dependent parameter and a non-smooth
      function of the underlying generative distribution. These features introduce
      additional variability that is not accounted for by standard methods for
      conducting statistical inference, for example, the bootstrap or normal
      approximations, if applied without adjustment. Our purpose is to provide a
      feasible method for constructing valid confidence intervals (CIs) for this
      quantity of practical interest. METHODS: We propose a conceptually simple and
      computationally feasible method for constructing valid CIs for the Value of an
      estimated DTR based on subsampling. The method is self-tuning by virtue of an
      approach called the double bootstrap. We demonstrate the proposed method using a
      series of simulated experiments. RESULTS: The proposed method offers considerable
      improvement in terms of coverage rates of the CIs over the standard bootstrap
      approach. LIMITATIONS: In this article, we have restricted our attention to Q
      learning for estimating the optimal DTR. However, other methods can be employed
      for this purpose; to keep the discussion focused, we have not explored these
      alternatives. CONCLUSION: Subsampling-based CIs provide much better performance
      compared to standard bootstrap for the Value of an estimated DTR.

PMID- 24925084
TI  - Association of sedentary behavior time with ideal cardiovascular health: the
      ORISCAV-LUX study.
AB  - BACKGROUND: Recently attention has been drawn to the health impacts of time spent
      engaging in sedentary behaviors. No studies have examined sedentary behaviors in
      relation to the newly defined construct of ideal cardiovascular health, which
      incorporates three health factors (blood pressure, total cholesterol, fasting
      plasma glucose) and four behaviors (physical activity, smoking, body mass index,
      diet). The purpose of this study was to examine associations between sedentary
      behaviors, including sitting time, and time spent viewing television and in front
      of a computer, with cardiovascular health, in a representative sample of adults
      from Luxembourg. METHODS: A cross-sectional analysis of 1262 participants in the
      Observation of Cardiovascular Risk Factors in Luxembourg study was conducted, who
      underwent objective cardiovascular health assessments and completed the
      International Physical Activity Questionnaire. A Cardiovascular Health Score was
      calculated based on the number of health factors and behaviors at ideal levels.
      Sitting time on a weekday, television time, and computer time (both on a workday
      and a day off), were related to the Cardiovascular Health Score. RESULTS: Higher
      weekday sitting time was significantly associated with a poorer Cardiovascular
      Health Score (p = 0.002 for linear trend), after full adjustment for age, gender,
      education, income and occupation. Television time was inversely associated with
      the Cardiovascular Health Score, on both a workday and a day off (p = 0.002 for
      both). A similar inverse relationship was observed between the Cardiovascular
      Health Score and computer time, only on a day off (p = 0.04). CONCLUSION: Higher
      time spent sitting, viewing television, and using a computer during a day off may
      be unfavorably associated with ideal cardiovascular health.

PMID- 24925085
TI  - New environment-sensitive multichannel DNA fluorescent label for investigation of
      the protein-DNA interactions.
AB  - Here, we report the study of a new multichannel DNA fluorescent base analogue 3
      hydroxychromone (3HC) to evaluate its suitability as a fluorescent reporter probe
      of structural transitions during protein-DNA interactions and its comparison with
      the current commercially available 2-aminopurine (aPu), pyrrolocytosine (Cpy) and
      1,3-diaza-2-oxophenoxazine (tCO). For this purpose, fluorescent base analogues
      were incorporated into DNA helix on the opposite or on the 5'-side of the damaged
      nucleoside 5,6-dihydrouridine (DHU), which is specifically recognized and removed
      by Endonuclease VIII. These fluorophores demonstrated different sensitivities to
      the DNA helix conformational changes. The highest sensitivity and the most
      detailed information about the conformational changes of DNA induced by protein
      binding and processing were obtained using the 3HC probe. The application of this
      new artificial fluorescent DNA base is a very useful tool for the studies of
      complex mechanisms of protein-DNA interactions. Using 3HC biosensor, the kinetic
      mechanism of Endonuclease VIII action was specified. 

PMID- 24925086
TI  - Age- and sex-dependence of dopamine release and capacity for recovery identified
      in the dorsal striatum of C57/Bl6J mice.
AB  - The dorsal striatum is the main input structure of the basal ganglia and the
      major target area of dopaminergic projections originating in the substantia nigra
      pars compacta. Heavily involved in the regulation of voluntary movement and habit
      formation, this structure is of strong importance in Parkinson's disease,
      obsessive-compulsive disorder, Tourette's syndrome and addiction. The C57/Bl6J
      mouse strain, the most commonly used strain in preclinical research today, is
      frequently used as a model organism for analysis of dopaminergic parameters
      implicated in human pathophysiology. Several components of the dopamine system
      have been shown to vary with age and sex, however knowledge of the contribution
      of these factors for dopamine release kinetics in the C57/Bl6J mouse strain is
      lacking. In the present study, we used an intracranial KCl-stimulation challenge
      paradigm to provoke release from dopaminergic terminals in the dorsal striatum of
      anaesthetized C57/Bl6J mice. By high-speed in vivo chronoamperometric recordings,
      we analyzed DA release parameters in male and female mice of two different ages.
      Our experiments demonstrate elevated DA amplitudes in adult compared to young
      mice of both sexes and higher DA amplitudes in females compared to males at both
      ages. Adult mice exhibited higher recovery capabilities after repeated
      stimulation than did young mice and also showed a lower variability in the
      kinetic parameters trise and t80 between stimulations. These results identified
      age- and sex- dimorphisms in DA release parameters and point to the importance of
      taking these dimorphisms into account when utilizing the C57/Bl6J mouse strain as
      model for neurological and neuropsychiatric disorders. 

PMID- 24925087
TI  - Cone-beam CT hepatic arteriography in chemoembolization for hepatocellular
      carcinoma: angiographic image quality and its determining factors.
AB  - PURPOSE: To analyze image quality and the factors that determine it for cone-beam
      computed tomography (CT) hepatic arteriography in chemoembolization for
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From September 2009
      December 2010, 399 consecutive patients referred for chemoembolization of HCC
      were scheduled for cone-beam CT scan. There were 12 patients (3%) excluded
      because of difficulty with breath-hold. Of the 387 patients who underwent cone
      beam CT hepatic arteriography, 100 patients were ultimately included in the study
      according to inclusion criteria. Maximum intensity projection images were scored
      for image quality of each segmental hepatic artery. Potential determining factors
      for image quality were diaphragmatic motion, portal vein enhancement, and hepatic
      artery-to-parenchyma enhancement ratio. The flow rate of contrast media, x-ray
      delay, and location of the catheter tip were also evaluated. RESULTS: It was
      possible to trace at least subsegmental hepatic arteries in 625 of 700 segments
      (89.3%) on cone-beam CT hepatic arteriography. Diaphragmatic motion, prominent
      portal vein enhancement, and low hepatic artery-to-parenchyma enhancement ratio
      worsened image quality (P < .001, P = .022, and P = .017). Owing to cardiac
      motion artifacts, image quality of the left lateral segments (S2 and S3) was
      poorer compared with the remaining hepatic segments (S4-S8). CONCLUSIONS: In most
      cases, the quality of cone-beam CT hepatic arteriography images was good enough
      to trace subsegmental hepatic arteries at a minimum. Respiratory and cardiac
      motion, portal vein enhancement, and hepatic artery-to-parenchyma enhancement
      ratio significantly affected the image quality of cone-beam CT hepatic
      arteriography.

PMID- 24925088
TI  - Accuracy of positional correction for the floor-mounted kV X-ray IGRT system in
      angled couch positions.
AB  - Stereotactic irradiation (STI) requires high geometric accuracy. We evaluated the
      positional correction accuracy after treatment couch rotation for non-coplanar
      STI with a frameless mask. A steel ball was embedded as a virtual target in a
      head phantom with a human cranial bone structure, and the head phantom was placed
      in the isocenter of the treatment-planning system with the image-guide system.
      The Winston-Lutz test at treatment couch angles of +/-90 degrees , +/-45 degrees
      , and 0 degrees  was performed, and the amount of displacement from the center
      position at the treatment couch angle of 0 degrees  was calculated. After
      treatment couch rotation through each treatment couch angle, the amount of center
      displacement was compared between cases with and without a positional correction
      by the image-guide system, and then the accuracy of the positional correction
      after treatment couch rotation was examined. The maximum amount of three
      dimensional displacement without and with positional correction after treatment
      couch rotation was 0.52 mm at a treatment couch angle of -90 degrees  and 0.49 mm
      at a treatment couch angle of -45 degrees . These results indicate that the image
      guide system provides accuracy within about 0.50 mm regardless of the positional
      correction even after rotation of the treatment couch.

PMID- 24925089
TI  - Histone demethylase Jumonji D3 (JMJD3/KDM6B) at the nexus of epigenetic
      regulation of inflammation and the aging process.
AB  - Histone methylation is involved in the epigenetic control of immune responses and
      cellular senescence. Jumonji domain-containing protein 3 (JMJD3), also called
      lysine-specific demethylase 6B (KDM6b), is an inducible histone demethylase which
      enhances immune responses and can trigger cellular senescence. JMJD3 potentiates
      gene expression by demethylating repressive H3K27me3 epigenetic marks in
      promoters and gene bodies. Moreover, JMJD3 also stimulates transcription in a
      demethylase-independent manner by mediating interactions between chromatin
      modifiers. JMJD3 can enhance both pro-inflammatory and anti-inflammatory
      responses by targeting distinct transcription factors in a context-dependent
      manner in gene promoters. For instance, JMJD3 can induce macrophage M2
      polarization via STAT6 signaling. JMJD3 also interacts with T-bet factor and
      induces Th1 differentiation of CD4(+) T cells. Moreover, JMJD3 can activate TGF
      beta signaling through the SMAD3 pathway. Conversely, JMJD3 displaces polycomb
      complexes from the INK4 box, which induces the expression of INK4a and triggers
      cellular senescence. JMJD3 can also enhance the nuclear localization of p53 and
      thus regulate its function. The control of INK4 box and p53 is closely related to
      the regulation of the aging process. We will briefly review the inducible
      properties of JMJD3 expression and then focus on the role of JMJD3 in the
      regulation of inflammation and senescence through different signaling pathways.
      We emphasize that an inflammatory milieu and cellular stress can enhance immune
      responses and provoke cellular senescence via epigenetic regulation through JMJD3
      activation. 

PMID- 24925090
TI  - Effect of opicapone and entacapone upon levodopa pharmacokinetics during three
      daily levodopa administrations.
AB  - BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O
      methyltransferase (COMT) inhibitor. The purpose of this study was to compare the
      levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition
      either following repeated doses of opicapone or concomitant administration with
      entacapone. METHODS: A randomized, double-blind, gender-balanced, parallel-group
      study was performed in 4 groups of 20 healthy subjects each. Four subjects in
      each group received placebo during the entire study. Sixteen subjects in one
      group received placebo once daily for 11 days and on day 12, 200 mg entacapone
      concomitantly with each levodopa/carbidopa dose (three times separated by a 5-h
      interval). Sixteen subjects in each of the remaining three groups received
      respectively 25, 50, and 75 mg opicapone once daily for 11 days and on day 12,
      placebo concomitantly with each levodopa/carbidopa dose. RESULTS: Levodopa
      minimum plasma concentration (Cmin) for each levodopa/carbidopa dose and for the
      mean of all levodopa/carbidopa doses increased substantially with all active
      treatments (entacapone and opicapone) when compared to the control group
      (placebo), with values ranging from 1.7-fold (200 mg entacapone) to 3.3-fold (75
      mg opicapone). No statistical difference was found for levodopa peak of systemic
      exposure (as assessed by maximum observed plasma concentration (Cmax)) between
      all active treatments and placebo. A significant increase in the levodopa extent
      of systemic exposure (as assessed by concentration-time curve (AUC)) occurred
      with all opicapone treatments in relation to placebo. No statistical difference
      was found for levodopa AUC when entacapone was compared to placebo. When compared
      to entacapone, both 50 and 75 mg opicapone presented a significant increase for
      the levodopa AUC. All active treatments significantly inhibited both peak (as
      assessed by Emax) and extent (as assessed by effect-time curve (AUEC)) of the
      COMT activity in relation to placebo. When compared to entacapone, all opicapone
      treatments significantly decreased the extent (AUEC) of the COMT activity due to
      a long-lasting and sustained effect. The tolerability profile was favorable for
      all active treatments. CONCLUSION: Opicapone, a novel third generation COMT
      inhibitor, when compared to entacapone, provides a superior response upon the
      bioavailability of levodopa associated to more pronounced, long-lasting, and
      sustained COMT inhibition. The tolerability profile was favorable. On the basis
      of the results presented in this study and along with the earlier pharmacology
      studies, it is anticipated that opicapone adjunct therapy at the dosages of 25
      and 50 mg will provide an enhancement in levodopa availability that will
      translate into clinical benefit for Parkinson's disease patients.

PMID- 24925091
TI  - Potentially inappropriate medications and adverse drug reactions in the elderly:
      a study in a PharmacoVigilance database.
AB  - BACKGROUND: Lists of potentially inappropriate medications (PIM) in the elderly
      were developed in order to identify patients and/or drugs at risk of adverse drug
      reactions (ADRs) or inefficacy. However, the relationship between PIMs and ADRs
      remains discussed. We hypothesized that PIM use is associated with more ADRs than
      other prescriptions. METHODS: All ADRs registered by the Midi-Pyrenees
      PharmacoVigilance Center between the 1st January and the 30th June 2012 in
      patients >=75 years were included. Data on patients (age, gender, Charlson
      comorbidity index), drugs (number, ATC classification, Laroche PIM
      classification) and ADRs (type, seriousness, mechanisms) were analyzed. RESULTS:
      Among the 923 ADRs recorded, 272 (29.5%) were in patients >=75 years. Mean age
      was 83.5 +/- 5.5 years. Most of them (59%) were females. Mean Charlson index was
      5.6 +/- 2.0 by ADR report. These 272 prescriptions involved 1,775 drugs [mean
      value, 6.5 (+/-3.4) drugs by ADR report] with 129 (7.3%) PIM. Main PIM classes
      were nervous (n = 98, 76.0%) and cardiovascular (17.8%) drugs, including 32
      atropinics (23.4%). ADR-associated drugs were mainly antithrombotics,
      antibacterials, and analgesics for non-PIM drugs whereas PIM-associated ADRs were
      mainly observed with digoxine, psycholeptics, and psychoanaleptics. ADRs were
      mainly found with non-PIM drugs (89.3%). Associated factors were the number of
      drugs for PIMs and the number of PIMs for PIM-induced ADRs. CONCLUSION: Out of
      the ADR reports registered in the Midi-Pyrenees PharmacoVigilance Database for
      patients >=75 years, 1 drug out of 12 is potentially inappropriate (mainly
      benzodiazepines, imipraminic antidepressants, and atropinic drugs). PIM use is
      not associated with more ADRs' reports than other prescriptions.

PMID- 24925092
TI  - Anxiety sensitivity and fear of pain in paediatric headache patients.
AB  - BACKGROUND: Recent research suggests that anxiety sensitivity (AS) may be a
      critical factor in the maintenance of chronic pain. Converging lines of evidence
      also propose a relationship between AS and fear of pain (FOP) that may result
      from interoceptive fear conditioning in interoceptively biased individuals. While
      some AS and FOP research has been carried out in adults, literature exploring
      this relationship is sparse in clinical paediatric populations. METHODS: This
      study investigated the hypotheses that FOP mediates the relationships between AS
      and disability as well as AS and somatization in children and adolescents with
      chronic headache pain. Mediation models were investigated using bootstrap
      regression analyses. RESULTS: Results indicate that the AS-disability
      relationship is mediated by FOP, whereas AS seems to contribute both directly and
      indirectly to somatization. CONCLUSION: These results provide evidence for the
      pivotal role of AS in the paediatric chronic pain model. The findings of this
      study further emphasize the application of the fear-avoidance model in children
      and provide new evidence for the critical role of AS in a paediatric headache
      population.

PMID- 24925093
TI  - Tricresyl phosphate and the aerotoxic syndrome of flight crew members--current
      gaps in knowledge.
AB  - Tricresyl phosphate (TCP), and in particular its tri-ortho substituted isomer
      (o,o,o-TCP), has been frequently used in aircraft engine oil. Bleed air, provided
      to the flight deck and cabin can contain traces of TCP. TCP can cause neurotoxic
      effects in humans. Regularly, airline pilots complain about loss of memory,
      headaches, dizziness, tunnel vision and other neurotoxic effects. The
      concentrations of TCP reported in flight deck air (max. ca. 50-100 ng m(-3) total
      TCP) do not exceed provisional toxicity thresholds. These thresholds, however,
      contain a very high uncertainty and need further underpinning. The many non
      detects and relatively low TCP concentrations reported suggest that TCP on its
      own is not likely to be responsible for the reported health problems of pilots.
      Specific conditions in air planes and other toxic compounds present in bleed air,
      whether or not in combination with TCP, may be responsible for the reported
      neurotoxic syndromes. Sensitivity of individuals seems to be an important factor
      as well. The clinical signs observed with a selected group of pilots are serious
      enough to call for further elucidation of this issue.

PMID- 24925095
TI  - Breast cancer screening: time for rational discourse.

PMID- 24925094
TI  - Acupuncture for menopausal vasomotor symptoms: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Hot flushes and night sweats (vasomotor symptoms) are common
      menopausal symptoms, often causing distress, sleep deprivation and reduced
      quality of life. Although hormone replacement therapy is an effective treatment,
      there are concerns about serious adverse events. Non-hormonal pharmacological
      therapies are less effective and can also cause adverse effects. Complementary
      therapies, including acupuncture, are commonly used for menopausal vasomotor
      symptoms. While the evidence for the effectiveness of acupuncture in treating
      vasomotor symptoms is inconclusive, acupuncture has a low risk of adverse
      effects, and two small studies suggest it may be more effective than non
      insertive sham acupuncture. Our objective is to assess the efficacy of needle
      acupuncture in improving hot flush severity and frequency in menopausal women.
      Our current study design is informed by methods tested in a pilot study.
      METHODS/DESIGN: This is a stratified, parallel, randomised sham-controlled trial
      with equal allocation of participants to two trial groups. We are recruiting 360
      menopausal women experiencing a minimum average of seven moderate hot flushes a
      day over a seven-day period and who meet diagnostic criteria for the Traditional
      Chinese Medicine diagnosis of Kidney Yin deficiency. Exclusion criteria include
      breast cancer, surgical menopause, and current hormone replacement therapy use.
      Eligible women are randomised to receive either true needle acupuncture or sham
      acupuncture with non-insertive (blunt) needles for ten treatments over eight
      weeks. Participants are blinded to treatment allocation. Interventions are
      provided by Chinese medicine acupuncturists who have received specific training
      on trial procedures. The primary outcome measure is hot flush score, assessed
      using the validated Hot Flush Diary. Secondary outcome measures include health
      related quality of life, anxiety and depression symptoms, credibility of the sham
      treatment, expectancy and beliefs about acupuncture, and adverse events.
      Participants will be analysed in the groups in which they were randomised using
      an intention-to-treat analysis strategy. DISCUSSION: Results from this trial will
      significantly add to the current body of evidence on the role of acupuncture for
      vasomotor symptoms. If found to be effective and safe, acupuncture will be a
      valuable additional treatment option for women who experience menopausal
      vasomotor symptoms. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry ACTRN12611000393954 11/02/2009.

PMID- 24925096
TI  - Novel biosensors based on optimized glycine oxidase.
AB  - Glycine is involved in several physiological functions, e.g. as a
      neurotransmitter in the central nervous system, and sarcosine has been identified
      as a differential metabolite greatly enhanced during prostate cancer progression
      and metastasis. Glycine oxidase from Bacillus subtilis (GO) was engineered with
      the final aim of producing specific analytical systems to detect these small
      achiral amino acids. Based on in silico analysis, site-saturation mutagenesis was
      independently performed at 11 positions: a total of 16 single-point GO variants
      were analyzed. Significantly improved kinetic parameters were observed on glycine
      for the A54R, H244K-N-Q-R, Y246W and M261R variants. The introduction of multiple
      mutations then identified the H244K/M261R variant showing a 5.4-fold increase in
      maximal activity on glycine. With sarcosine as substrate, a number of single
      point variants showed increased maximal activity and/or affinity: the kinetic
      efficiency was increased 6-fold for the M49L variant. Two GO variants with a high
      substrate specificity ratio for glycine (versus sarcosine, i.e. H244K GO) or for
      sarcosine (versus glycine, i.e. M49L GO) combined with high substrate affinity
      were used to set up a simple fluorescence-based biosensor. This optical sensing
      assay represents a novel, inexpensive and fast tool to assay glycine or sarcosine
      concentrations in biological samples (detection limit <= 0.5 MUm).

PMID- 24925098
TI  - How does reverse shoulder replacement change the range of motion in activities of
      daily living in patients with cuff tear arthropathy? A prospective optical 3D
      motion analysis study.
AB  - BACKGROUND: Reverse total shoulder arthroplasty (RSA) can improve function in
      cuff tear arthropathy (CTA) shoulders, but limited exact data are available about
      the maximum values in 3D motion analysis, and as to how improvements translate
      into the normal range of motion (ROM) in activities of daily living (ADLs).
      METHODS: This study included nine consecutive patients (n = 9) who received RSA
      for CTA without muscle transfers. We measured shoulder movement by a novel 3D
      motion analysis using the Heidelberg upper extremity model (HUX) which can
      eliminate compensatory movements of the scapula, and the trunk. The measurement
      included active maximum values, and four ADLs. RESULTS: Comparing the pre- to the
      1-year postoperative status, RSA was associated with a significant increase in
      the mean maximum values for active flexion of about 43 degrees  (SD +/- 31) from
      66 degrees  to 109 degrees  (p = 0.001), for active abduction of about 37 degrees
      (SD +/- 26) from 57 degrees  to 94 degrees  (p = 0.001), and for the active
      adduction of about 28 degrees  (SD +/- 10) from 5 degrees  to 33 degrees  (p =
      0.002). Comparing the preoperative to the postoperative ROM in the ADLs in
      flexion/extension, ROM improved significantly in all ADLs, in abduction/adduction
      in three of four ADLs. No significant changes were observed in internal/external
      rotation in any ADLs. CONCLUSION: RSA improves the active maximum ROM for
      flexion, abduction, and adduction. The patients are able to take advantage of
      this ROM increase in ADLs in flexion and in most ADL in abduction, but only in
      trend in internal and external rotation.

PMID- 24925100
TI  - Fine structure in diabetic retinopathy lesions as observed by adaptive optics
      imaging. A qualitative study.
AB  - PURPOSE: Diabetic retinopathy is diagnosed by fundus photography and optical
      coherence tomography (OCT) scanning. However, adaptive optics (AO) imaging can be
      expected to add new aspects to the knowledge of diabetic retinopathy because
      photographic resolution is improved by reducing the influence of optical
      aberrations on retinal imaging. METHODS: Nineteen patients with diabetes mellitus
      were subjected to fundus photography, OCT scanning and AO imaging. The fundus
      photographs were scaled to the same magnification as that of the AO image, and
      qualitative aspects of AO images of each retinopathy lesion observed on fundus
      photographs and OCT scans were assessed. RESULTS: All red lesions on fundus
      photographs appeared on AO images as dark hyporeflective elements, but it could
      not be verified whether lesions represented haemorrhages or microaneurysms. The
      smallest of these lesions were circular with a size corresponding to that of
      blood cells. Hard exudates had irregular surfaces with buddings of various sizes
      protruding from the lesions. Areas of retinal oedema observed by fundus imaging
      and OCT scanning resulted in blurring of AO images, but cystoid spaces observed
      by OCT could be seen on AO images to have a sharp delimitation with a darker
      hyporeflective rim at the internal lining of the cyst wall. CONCLUSION: AO
      imaging may potentially assist in detecting diabetic retinopathy at an earlier
      stage, may help elucidating the pathophysiology of the diseases and may be used
      for evaluating the effects of clinical interventions on diabetic retinopathy and
      other retinal vascular diseases.

PMID- 24925101
TI  - Women in otolaryngology.

PMID- 24925102
TI  - Acute esotropia, convergence-retraction nystagmus and contraversive ocular tilt
      reaction from a paramedian thalamomesencephalic infarct.

PMID- 24925103
TI  - Optimal target range for blood glucose in hyperglycaemic patients in a
      neurocritical care unit.
AB  - BACKGROUND: Hyperglycaemia is common among patients with critical neurological
      injury, even if they have no history of diabetes. The optimal target range for
      normalizing their blood glucose is unknown. METHODS: Retrospective data were
      extracted from 890 hyperglycaemic individuals (glucose > 200 mg/dL) admitted to
      neuroscience critical care unit (NCCU) and these patients were divided into two
      groups: intensive glucose control group with target glucose of < 140 mg/dL
      achieved and moderate control with glucose levels 140-180 mg/dL. The groups were
      also stratified according to the hyperglycaemia type (pre-existing diabetes or
      stress-related). We defined the primary endpoint as death from any cause during
      NCCU admission. RESULTS: In NCCU, tighter control of blood glucose at <= 140
      mg/dL was associated with increased, mortality of individuals with pre-existing
      diabetes compared with moderate control [29 of 310 patients (9.4%) vs 15 of 304
      patients (4.9%), p = 0.034]. Patient age [adjusted odds ratio (OR) = 1.12; 95%
      confidence interval (CI) = 1.05-1.19; p < 0.001], level of glycated haemoglobin
      (adjusted OR = 1.24; 95% CI = 1.04-1.48; p = 0.017) and hypoglycaemia (adjusted
      OR = 10.3; 95% CI = 2.92-36.6; p < 0.001) were positively associated with higher
      mortality. Death rate was lower among stress-related hyperglycaemic patients with
      tighter glucose controlled at <= 140 mg/dL [6 of 140 patients (4.3%) vs 15 of 136
      patients (11.0%), p = 0.035]. CONCLUSION: A differential association is evident
      between glucose levels and mortality in diabetes and stress-related
      hyperglycaemia patients. However, given the observational nature of our work, no
      clinical recommendations can be given and prospective studies are required to
      further investigate these findings.

PMID- 24925099
TI  - Coreceptor usage, diversity, and divergence in drug-naive and drug-exposed
      individuals from Malawi, infected with HIV-1 subtype C for more than 20 years.
AB  - There are few cohorts of individuals who have survived infection with HIV-1 for
      more than 20 years, reported and followed in the literature, and even fewer from
      Africa. Here we present data on a cohort of subtype C-infected individuals from
      rural northern Malawi. By sequencing multiple clones from long-term survivors at
      different time points, and using multiple genotyping approaches, we show that 5
      of the 11 individuals are predicted as CXCR4 using (by >=3/5 predictors) but only
      one individual is predicted as CXCR4 using by all five algorithms. Using any one
      genotyping approach overestimates the number of predicted CXCR4 sequences.
      Patterns of diversity and divergence were variable between the HIV-1 long-term
      survivors with some individuals showing very small amounts of variation and
      change, and others showing a greater amount; both patterns are consistent with
      what has been described in the literature.

PMID- 24925105
TI  - Predictors of respiratory epithelial adenomatoid hamartomas of the olfactory
      clefts in patients with nasal polyposis.
AB  - OBJECTIVES/HYPOTHESIS: To look for predictors of respiratory epithelial
      adenomatoid hamartomas (REAH) development in patients operated for nasal
      polyposis (NP) by adjusting on confounding factors. STUDY DESIGN: Prospective
      study. METHODS: One hundred and six patients with NP, endoscopically operated
      between September 2009 and March 2012 on the ethmoidal labyrinths and olfactory
      clefts, were enrolled in this study. Clinical data was collected 1 day prior to
      surgery by using a standard grid without knowledge of any histological features.
      Patients were then divided into two groups based on operative and pathological
      reports: with and without REAH in the olfactory cleft (REAH-OC). The multivariate
      logistic regression model was used to assess independent factors linked to the
      presence of REAH-OC in patients with NP. RESULTS: The mean duration of NP disease
      in patients with REAH-OC was about 13.95 +/- 10.8 years versus 5.7 +/- 5.6 years
      in patients without REAH-OC (P < 0.0001). Seventy-four percent of patients with
      REAH-OC had undergone one or more NP-related surgeries in their lifetime, in
      contrast with 49.21% of patients without REAH-OC (P = 0.009). According to the
      multivariate logistic regression analysis, those patients experiencing NP >= 10
      years (OR 4.0, 95% CI 1.304-12.062, P = 0.015) and those with asthma (OR 2.5, 95%
      CI 1.004-6.29, P < 0.05) were at an increased risk of developing REAH-OC.
      CONCLUSION: The development of REAH in patients with NP appears as a specific
      disease of the mucosa of the OC, induced by a long-lasting and/or severe
      inflammation of the olfactory clefts. LEVEL OF EVIDENCE: 4.

PMID- 24925106
TI  - Evolution of aging: individual life history trade-offs and population
      heterogeneity account for mortality patterns across species.
AB  - A broad range of mortality patterns has been documented across species, some even
      including decreasing mortality over age. Whether there exist a common denominator
      to explain both similarities and differences in these mortality patterns remains
      an open question. The disposable soma theory, an evolutionary theory of aging,
      proposes that universal intracellular trade-offs between maintenance/lifespan and
      reproduction would drive aging across species. The disposable soma theory has
      provided numerous insights concerning aging processes in single individuals. Yet,
      which specific population mortality patterns it can lead to is still largely
      unexplored. In this article, we propose a model exploring the mortality patterns
      which emerge from an evolutionary process including only the disposable soma
      theory core principles. We adapt a well-known model of genomic evolution to show
      that mortality curves producing a kink or mid-life plateaus derive from a common
      minimal evolutionary framework. These mortality shapes qualitatively correspond
      to those of Drosophila melanogaster, Caenorhabditis elegans, medflies, yeasts and
      humans. Species evolved in silico especially differ in their population diversity
      of maintenance strategies, which itself emerges as an adaptation to the
      environment over generations. Based on this integrative framework, we also derive
      predictions and interpretations concerning the effects of diet changes and heat
      shock treatments on mortality patterns. 

PMID- 24925104
TI  - Clinical and non-targeted metabolomic profiling of homozygous carriers of
      Transcription Factor 7-like 2 variant rs7903146.
AB  - An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in
      metabolic actions of various tissues, in particular of the liver, has recently
      been demonstrated by functional animal studies. Accordingly, the TT diabetes risk
      allele may lead to currently unknown alterations in human. Our study revealed no
      differences in the kinetics of glucose, insulin, C-peptide and non-esterified
      fatty acids during an OGTT in homozygous participants from a German diabetes risk
      cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15)
      genotype. However, beta-cell function was impaired for TT carriers. Covering more
      than 4000 metabolite ions the plasma metabolome did not reveal any differences
      between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146
      on the systemic level in humans, but confirms the role in the pathogenesis of
      type 2 diabetes in humans as a mechanism impairing insulin secretion. 

PMID- 24925107
TI  - Synthesis of the C10-C24-bis-spiroacetal core of 13-desmethyl spirolide C based
      on a sila-Stetter-acetalization process.
AB  - Synthesis of the bis-spiroacetal core of 13-desmethyl spirolide C has been
      completed based on a sila-Stetter-acetalization process. The acylsilane and enone
      partners in the Stetter reaction were prepared in 7 and 11 steps, respectively,
      from (S) and (R)-aspartic acid. The quaternary center at C19 in the enone moiety
      was controlled by relying on the Seebach's chiral self-reproduction method using
      an enantiopure (S)-lactic acid based dioxolanone. The final acid-catalyzed
      spiroacetalization provided the desired spiroacetal as a mixture of
      diastereoisomers in 13 linear steps. Whatever the conditions used, the non
      natural transoid isomer was formed preferentially. However, both cisoid and
      transoid isomers were isolated pure and their structure assigned unambiguously
      through NMR spectroscopic studies. 

PMID- 24925108
TI  - Evaluation of BDE-47 hydroxylation metabolic pathways based on a strong electron
      withdrawing pentafluorobenzoyl derivatization gas chromatography/electron capture
      negative ionization quadrupole mass spectrometry.
AB  - Understanding the metabolic pathways of polybrominated diphenyl ethers (PBDEs) is
      a key issue in the evaluation of their cytotoxicity after they enter the biota.
      In order to obtain more information concerning the metabolic pathways of PBDEs,
      we developed a strong electron-withdrawing pentafluorobenzoyl (PFBoyl)
      derivatization capillary gas chromatography/electron capture negative ionization
      quadrupole mass spectrometry (GC/ECNI-qMS). PFBoyl esterification greatly
      improves separation of the metabolites of PBDEs such as hydroxylated PBDEs (OH
      PBDEs) and bromophenols (BPs) metabolites in rat liver microsomes (RLMs). On the
      other hand, the strong electron-withdrawing property of PFBoyl derivatized on OH
      PBDEs and/or BPs makes cleavage of the ester bond on ECNI easier resulting in
      higher abundance of the structure-informative characteristic fragment ions at a
      high m/z region, which facilitate the identification of OH-PBDEs metabolites.
      Subsequent quantification can be performed by monitoring not only 79Br- (or 81Br
      ) but also their characteristic fragment ions, achieving more accurate isotope
      dilution quantification using GC/ECNI-qMS. These merits allow us to identify
      totally 12 metabolites of BDE-47, a typical example of PBDEs, in the RLMs in
      vitro incubation systems. In addition to the already known metabolites of BDE-47,
      one dihydroxylated 3,6-di-OH-BDE-47 and one dihydroxylated 3,5-di-OH
      tetrabrominated dioxin were found. Moreover, the second hydroxylation took place
      on the same bromophenyl ring, where the first hydroxyl group was located, and was
      further confirmed via the identification of the dihydroxylated 2',6'-di-OH-BDE-28
      of an asymmetric 2'-OH-BDE-28. This methodological development and its subsequent
      findings of the metabolic pathways of BDE-47 provided experimental evidence for
      understanding its dioxin-like behavior and endocrine disrupting risk.

PMID- 24925109
TI  - Functional analysis of maternal aggression in the house mouse (mus musculus
      domesticus).
AB  - The presumed function of maternal aggression as a means to protect the young from
      infanticidal conspecifics was tested. Lactating females attacked male intruders
      regardless of their potential for infanticide and intrasexual aggression (as
      previously screened). The level of aggression of the male intruder rather than
      his infanticidal potential, influenced both the mother's latency to attack and
      the possibility of successful protection of her young. A lactating female's
      attack on a male, but not on a female, intruder was reduced by the presence of
      her mate. Lactating females did not attack male intruders when their mates were
      not aggressive towards them. Thus, maternal attack appears to be modulated by the
      aggressive characteristics of both the stud and the intruder male rather than as
      a response to the potential risk for the litter. This suggests that lactating
      female attack on males is not only a counter-strategy to infanticide. In an
      evolutionary perspective, the possibility that this behavior may also involve
      intersexual selection mechanisms is discussed. 

PMID- 24925110
TI  - Fear reactions of ewes to photographic images.
AB  - The aim of this study was to analyse fear reactions of 18 adult Romanov ewes
      individually confronted with 3 visual stimuli, namely pictures of a human, of a
      sheep or of a traffic cone (control). These pictures were projected in real size
      on a wall of the test pen by means of a slide projector. Twenty-six behavioural
      items related to fear were recorded. Furthermore, fearfulness scores were
      calculated to compare the overall fear levels of the subjects when confronted
      with the photographic images. We hypothesized that if animals recognized a man or
      a sheep in the presented slides, fear reactions would be enhanced in the presence
      of the picture of a human and reduced in the presence of a sheep picture as
      compared with the control situation. Our results suggest that ewes may be able to
      recognize the sheep picture as a conspecific. For example, sniffings were
      primarily directed towards the anogenital region and the head. The reduced fear
      reactions of isolated ewes in the presence of a sheep picture is similar to that
      observed previously in the presence of real conspecifics. In contrast, they did
      not differ when sheep were confronted with a human or a control image, indicating
      that additional stimuli may be needed for the human image to be fear-eliciting. 

PMID- 24925111
TI  - Equivalence class formation as a function of the pronounceability of the sample
      stimulus.
AB  - The role of naming in stimulus equivalence was studied by varying the
      pronounceability of sample stimulus pseudowords. Experiment 1 compared three
      conditions: in the first, sample stimuli consisted of phonologically correct
      pseudowords; in the second, sample stimuli consisted of phonologically incorrect
      words; in the last, sample stimuli consisted of punctuation marks. Subjects
      exposed to pronounceable stimuli demonstrated equivalence class formation more
      quickly and with fewer errors than did other subjects. In Experiment 2, subjects
      were trained in equivalence-class formation using only non-phonological sample
      stimuli. Half the subjects were exposed to a pretraining procedure in which they
      read a list of non-phonological pseudowords aloud. Remaining subjects transcribed
      the same list of pseudowords - a procedure which equated exposure to the
      pseudowords, but did not necessarily encourage subjects to name them. Subjects
      who were pretrained with the read-aloud task made significantly fewer errors than
      those who transcribed the words. These data are consistent with the theory that
      equivalence class formation is mediated by verbal behavior. 

PMID- 24925112
TI  - Absence of temporal polyethism in the ponerine ant pachycondyla caffraria (Smith)
      (hymenoptera: formicidae): Early specialization of the foragers.
AB  - In the Ponerine Pachycondyla caffraria the behaviour of workers is independent of
      age. They leave the nest to forage a few days after eclosion, and some
      specialization appears in the young foragers. For the first five days, the callow
      workers stay in the nest chamber; they remain immobile, or groom themselves, or
      lick the larvae and pupae, which they transport from one part of the nest to
      another. Six or seven days after eclosion, some of the young workers remain
      inside the nest and occupy themselves with inside labour, while others leave the
      nest to forage, and collect sugar water or hunt for prey. The frequency of some
      behavioural acts which are performed by the young inside workers increases or
      decreases with age. 

PMID- 24925113
TI  - Contextual control of Pavlovian bidirectional occasion setting.
AB  - Three pigeons were trained in a lighted context on a bidirectional occasion
      setting task in which a tone feature (F) signaled food after the green keylight
      (L:G-, L:FG+) and no food after the red keylight (L:R+, L:FR-). They acquired the
      former feature-positive (F-P) discrimination and the latter feature-negative (F
      N) discrimination at almost equal speed. Another three birds were trained with a
      F-P discrimination task in a light context (L:G-, L:FG+) and with a F-N
      discrimination task in a dark context (D:G+, D:FG-). The keylight was always
      green and two contextual conditions were changed randomly trial by trial. In this
      training, the F-P discrimination was acquired faster than the F-N discrimination.
      Then, all birds received a more complex amalgam contingency in which all eight
      types of trials were presented in the session (D:R-, D:G+, D:FR+, D:FG-, L:R+,
      L:G-, L:FR-, L:FG+). After they learned the amalgam training, the outcomes of two
      trial types were changed (D:R+, D:G-), but this treatment failed to reverse the
      pattern of responding in the remaining trial types. 

PMID- 24925114
TI  - Psychological distance to reward: The aversiveness of the first component
      stimulus in a chain.
AB  - Pigeons served in two experiments examining the aversiveness of the first
      component stimulus (S1) in a fixed-time (FT) chained schedule using a two-key
      escape procedure. Responding on a chain key was reinforced by a chained schedule
      while pecking a switch key produced brief blackouts on the chain key. In
      Experiment 1, pigeons were first trained on a chain FT 30 s FT 30 s (i.e. overall
      duration 60 s) using the chain key alone (Phase I); then they were allowed to
      turn off the chain-key light by pecking the switch key without affecting
      reinforcement programmed by the chained schedule (Phase II); finally, the
      blackout contingency on the switch key was discontinued (Phase III). Results
      showed that pigeons pecked the switch key only during C1 but not C2 and this
      behavior was maintained only when the pecks produced blackouts of S1 (Phase II).
      Hence escaping from C1 was negatively reinforcing and the phenomenon was
      attributed to the aversiveness of S1. Experiment 2 assessed the effect of the
      overall duration of the chained schedule on switch-key responses using the same
      procedure. With the three durations investigated (20 s, 40 s and 60 s), results
      showed that the switch-key rate was a positive function of the overall duration.
      Thus the aversiveness of S1 increased as the duration lengthened. These findings
      are consistent with those from choice studies in that segmentation of a schedule
      extends its 'psychological distance to reward'. 

PMID- 24925115
TI  - Comparing behaviour in wild and laboratory strains of the house mouse: Levels of
      comparison and functional inference.
AB  - Many behavioural studies of laboratory house mice have sought functional
      explanations for their results. This raises the problem of the comparability of
      behaviour with that of wild house mice from whose naturally selected repertoire
      the behaviour of laboratory strains has been derived. This in turn requires
      careful choice of measures to ensure that subtle changes in response during the
      selection of laboratory strains are taken into account. A comparison of social
      behaviours showing kin bias in male mice of the CFLP laboratory strain shows that
      superficial measures based on totals over an arbitrary test period, a widely used
      procedure, can be misleading because they fail to control for differences in the
      tendency for CFLP and wild mice to encounter one another and the intensity of
      social responses when encounters do occur. Such differences may reflect different
      contexts and consequences of social responses in the two strains. 

PMID- 24925116
TI  - Pigeons' landmark use as revealed in a 'feature-positive', digitized landscape,
      touchscreen paradigm.
AB  - Two pigeons were trained to discriminate between a S - (a digitized image of a
      grassy field presented on a computer monitor) and a S + (a digitized image of the
      same field containing a tree, a set of flowers, and a log). The location of the
      pecks to the images was recorded by a touchscreen. Both subjects quickly learned
      the discrimination and concentrated their pecks to particular 'landmarks', one
      pigeon pecking the flowers, the other the tree. This result suggests that the use
      of digitized images of real-world geographic locations may help us to understand
      how animals use visual landmarks in spatial navigation, and, in more general
      terms, how animals perceive and remember in their natural environments. 

PMID- 24925117
TI  - Slide fastener reduction of graphene-oxide edges by calcium: insight from ab
      initio molecular dynamics.
AB  - The reduction of graphene oxide can be used as a simple way to produce graphene
      on a large scale. However, the numerous edges produced by the oxidation of
      graphite seriously degrade the quality of the graphene and its carrier transport
      property. In this work, the reduction of oxygen-passivated graphene edges and the
      subsequent linking of separated graphene sheets by calcium are investigated by
      using first-principles calculations. The calculations show that calcium can
      effectively remove the oxygen groups from two adjacent edges. The joining point
      of the edges serves as the starting point of the reduction and facilitates the
      reaction. Once the oxygen groups are removed, the crack is sutured. If the
      joining point is lacking, it becomes difficult to zip the separated fragments. A
      general electron-reduction model and a random atom-reduction model are suggested
      for these two situations. The present study sheds light on the reduction of
      graphene-oxide edges by using reactive metals to give large-sized graphene
      through a simple chemical reaction. 

PMID- 24925118
TI  - Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain
      tumors: a short temporal interval assessment.
AB  - PURPOSE: To determine the effect of intravenous administration of gadolinium (Gd)
      contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation
      of normal brain parenchyma vs. brain tumor following a short temporal interval.
      MATERIALS AND METHODS: Forty-four DWI studies using b values of 0 and 1000
      s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5
      min after the administration of Gd-DTPA on 62 separate lesions including 15
      meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of
      the brain tumor lesions and normal brain tissues were measured on pre- and
      postcontrast images. Statistical analysis using paired t-test between precontrast
      and postcontrast data were obtained on three brain tumors and normal brain
      tissue. RESULTS: The SNR and CNR of brain tumors and the SNR of normal brain
      tissue showed no statistical differences between pre- and postcontrast (P >
      0.05). The ADC values on the three cases of brain tumors demonstrated significant
      initial increase on the immediate time point (P < 0.01) and decrease on following
      the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value
      was still found at 3min and 5min time point in the meningioma group (P < 0.01)
      with gradual normalization over time. The ADC values of normal brain tissues
      demonstrated significant initial elevation on the immediately postcontrast DWI
      sequence (P < 0.01). CONCLUSION: Contrast medium can cause a slight but
      statistically significant change on the ADC value within a short temporal
      interval after the contrast administration. The effect is both time and lesion
      type dependent.

PMID- 24925119
TI  - Caution when defining prolonged downtime in out of hospital cardiac arrest as
      extracorporeal cardiopulmonary resuscitation becomes accessible and feasible.

PMID- 24925121
TI  - Soy food consumption, cardiometabolic alterations and carotid intima-media
      thickness in Chinese adults.
AB  - BACKGROUND AND AIM: The associations between soy food consumption,
      cardiometabolic disturbances and subclinical atherosclerosis remain controversial
      due to limited evidence. We examined the associations of habitual soy food
      consumption with cardiometabolic disturbances and carotid intima-media thickness
      (CIMT). METHODS AND RESULTS: We included 2939 subjects (2135 women and 804 men)
      aged 50-75 years in this community-based cross-sectional study. Dietary data and
      other covariates were collected using interviewer-administered questionnaires. We
      determined CIMT in relation to each subject's common carotid artery, internal
      carotid artery, carotid bifurcation, blood lipids, glucose and urine acid, blood
      pressure and waist circumference. A logistic regression model was applied to
      estimate the odd ratios (ORs) and 95% confidence intervals (CIs), and linear
      regression was used to estimate the regression coefficient and 95% CIs. After
      adjusting for potential confounders, we found that greater consumption of soy
      protein (6.1 vs. 0.5 g/d) was inverse associated with the presence of elevated
      total cholesterol (TC), dyslipidemia, abdominal obesity and hyperuricemia in
      women, and with abdominal obesity in men, although no significant sex-soy
      interactions were observed (P: 0.145-0.985). The consumption of soy protein and
      isoflavones was inversely associated with the number of cardiometabolic
      disturbances among women, but not men. There were no significant associations of
      soy protein and isoflavones with CIMT thickening and other cardiometabolic
      disturbances. CONCLUSION: Greater soy consumption was associated with a lower
      presence of elevated TC, dyslipidemia, hyperuricemia and less number of
      cardiometabolic disturbances components in women.

PMID- 24925120
TI  - Nut consumption, serum fatty acid profile and estimated coronary heart disease
      risk in type 2 diabetes.
AB  - BACKGROUND AND AIMS: Nut consumption has been associated with decreased risk of
      coronary heart disease (CHD) and type 2 diabetes which has been largely
      attributed to their healthy fatty acid profile, yet this has not been
      ascertained. Therefore, we investigated the effect of nut consumption on serum
      fatty acid concentrations and how these relate to changes in markers of glycemic
      control and calculated CHD risk score in type 2 diabetes. METHODS AND RESULTS:
      117 subjects with type 2 diabetes consumed one of three iso-energetic (mean 475
      kcal/d) supplements for 12 weeks: 1. full-dose nuts (50-100 g/d); 2. half-dose
      nuts with half-dose muffins; and 3. full-dose muffins. In this secondary
      analysis, fatty acid concentrations in the phospholipid, triacylglycerol, free
      fatty acid, and cholesteryl ester fractions from fasting blood samples obtained
      at baseline and week 12 were analyzed using thin layer and gas chromatography.
      Full-dose nut supplementation significantly increased serum oleic acid (OA) and
      MUFAs compared to the control in the phospholipid fraction (OA: P = 0.036; MUFAs:
      P = 0.024). Inverse associations were found with changes in CHD risk versus
      changes in OA and MUFAs in the triacylglycerol (r = -0.256, P = 0.011; r = 
      0.228, P = 0.024, respectively) and phospholipid (r = -0.278, P = 0.006; r = 
      0.260, P = 0.010, respectively) fractions. In the cholesteryl ester fraction,
      change in MUFAs was inversely associated with markers of glycemic control (HbA1c:
      r = -0.250, P = 0.013; fasting blood glucose: r = -0.395, P < 0.0001).
      CONCLUSION: Nut consumption increased OA and MUFA content of the serum
      phospholipid fraction, which was inversely associated with CHD risk factors and
      10-year CHD risk. CLINICAL TRIAL REG NO: NCT00410722, clinicaltrials.gov.

PMID- 24925123
TI  - Assessment of vascular and endothelial dysfunction in nutritional studies.
AB  - Vascular and endothelial dysfunction (VED) is emerging as a potential set of
      early markers of cardiovascular disease risk and tests for its measurement have
      been widely used in clinical research. The aim of this viewpoint is to describe
      and discuss the current usage of these measures in well-designed nutritional
      trials, using the potential relationship between fruit juice intake and VED as
      example. A search was conducted using the NHS evidence portal including studies
      published in English between January 1980 and October 2013. Only 10 suitable
      studies were selected, which investigated the effect of fruit juice intake on
      VED, among which 4 interventions used flow-mediated dilatation, 2 arterial
      stiffness, 2 a combination of arterial stiffness and flow-mediated dilatation, 2
      carotid intimal media thickness and 1 iontophoresis with laser Doppler. Despite
      minimal effects reported on classical CVD markers, such as lipids, 8 out of the
      10 identified studies reported an effect on endothelial function following juice
      consumption, indicating that VED tests can be effectively used in human dietary
      interventions to identify relationships between bioactive compounds from fruit
      and CVD risk. However, paucity of available data, scarcity of compound
      bioavailability and metabolism information, strong heterogeneity among
      experimental methodologies and a number of limitations to study designs, still
      limit the interpretation of the results obtained through these measures. Future,
      well-designed studies with greater attention to consider use of VED measures are
      needed to strengthen the utility of VED tests in nutrition research such as those
      investigating the impact of polyphenol-rich juices and CVD risk. 

PMID- 24925122
TI  - Sedentary time and markers of inflammation in people with newly diagnosed type 2
      diabetes.
AB  - BACKGROUND AND AIMS: We investigated whether objectively measured sedentary time
      was associated with markers of inflammation in adults with newly diagnosed type 2
      diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean
      age 59.0 +/- 9.7) who had been recruited to the Early ACTivity in Diabetes (Early
      ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin,
      soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and
      accelerometer-determined sedentary time and moderate-vigorous physical activity
      (MVPA) were measured at baseline and after six-months. Linear regression analysis
      was used to investigate the independent cross-sectional and longitudinal
      associations of sedentary time with markers of inflammation. At baseline,
      associations between sedentary time and IL-6 were observed in men and women, an
      association that was attenuated following adjustment for waist circumference.
      After 6 months of follow-up, sedentary time was reduced by 0.4 +/- 1.2 h per day
      in women, with the change in sedentary time predicting CRP at follow-up. Every
      hour decrease in sedentary time between baseline and six-months was associated
      with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6
      months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL
      6 in men and women with type 2 diabetes, and reducing sedentary time is
      associated with improved levels of CRP in women. Interventions to reduce
      sedentary time may help to reduce inflammation in women with type 2 diabetes.

PMID- 24925124
TI  - A low glycaemic load breakfast can attenuate cognitive impairments observed in
      middle aged obese females with impaired glucose tolerance.
AB  - BACKGROUND AND AIMS: There has been no systematic investigation of the individual
      and combined effects of impaired glucose tolerance (IGT) and obesity on cognitive
      function in the absence of ageing. The aims were to examine the effects of IGT
      and increased waist circumference on cognitive function in ostensibly healthy
      adults, and to investigate whether a low glycaemic load (GL) breakfast can
      attenuate cognitive impairments in these populations. METHODS AND RESULTS: Sixty
      five females aged 30-50 years were classified into one of four groups following
      waist circumference (WC) measurements and an oral glucose tolerance test: NGT/low
      WC (n = 25), NGT/high WC (n = 22), IGT/low WC (n = 9), IGT/high WC (n = 9).
      Memory, psychomotor and executive functions were examined 30 and 120 min after
      consuming low GL, high GL and water breakfasts according to a randomised,
      crossover, counterbalanced design. IGT was associated with impairment of verbal
      and spatial memory, and psychomotor function relative to females with NGT,
      independent of waist circumference. Increased waist circumference was associated
      with impairment of verbal memory and executive function relative to females with
      low WC, independent of IGT. Consumption of the LGL breakfast attenuated verbal
      memory impairment in the IGT/high WC group relative to the HGL breakfast and no
      energy control. CONCLUSION: Increased central adiposity and abnormalities in
      glucose tolerance preceding type 2 diabetes can have demonstrable negative
      effects on cognitive function, even in ostensibly healthy, middle-aged females.
      The potential for GL manipulations to modulate glycaemic response and cognitive
      function in type 2 diabetes and obesity merits further investigation.

PMID- 24925125
TI  - The impact of oral food challenge tests on food allergy health-related quality of
      life.
AB  - Food allergy health-related quality of life (FAQOL) has been shown to improve
      after food challenge, but it is unknown whether this improvement is attributed to
      the procedure itself. Using the Food Allergy Quality of Life Questionnaire-Parent
      Form, we assessed FAQOL changes over time for children who underwent food
      challenges in the only paediatric allergy clinic in Ireland. Of 54 children who
      had a food challenge between September 2012 and February 2013, 25 were positive
      (allergic) and 29 were negative (nonallergic). FAQOL improved significantly from
      2 months prechallenge to 2 months postchallenge for both groups, but began to
      decrease at 6 months postchallenge in allergic patients. Our findings confirm the
      positive therapeutic effect of the food challenge on FAQOL; however, the effect
      appears to wane between 2 and 6 months postchallenge in those confirmed food
      allergic, highlighting the importance of regular contact with families of food
      allergic children after the food challenge. 

PMID- 24925126
TI  - Clinical characteristics of rheumatoid arthritis patients undergoing cervical
      spine surgery: an analysis of National Database of Rheumatic Diseases in Japan.
AB  - BACKGROUND: The aim of this study was to examine the clinical characteristics of
      rheumatoid arthritis (RA) patients who underwent cervical spine surgery using a
      multicenter observational database. METHODS: We obtained data from a nationwide
      observational cohort database of patients with rheumatic diseases (National
      Database of Rheumatic Diseases by iR-net in Japan (NinJa)) for the fiscal years
      2003 to 2011. A total of 39 out of 60 patients who underwent cervical spine
      surgery for a RA-related cause and whose data were available for two consecutive
      years (to assess the preoperative patient status) were chosen as cases. Patients
      with a non-RA-related cause of surgery (e.g., trauma) were excluded. First, we
      compared the patient characteristics between the cases and total patients in the
      same fiscal year. Next, 106 eligible controls, who were defined as RA patients
      enrolled in the same fiscal year as the case subjects, who were matched for age,
      gender and disease duration (within +/-1 year), were selected. We compared the
      demographic data between the two groups. We also calculated the percentage of
      patients who underwent cervical spine surgery (surgeries/total number of
      patients) in fiscal years 2003 to 2011. RESULTS: Although the proportion of
      patients using biologics linearly increased during study period, the percentage
      of patients undergoing cervical spine surgeries remained unchanged, at
      approximately 0.15%. These cases had more tender joints (3 vs. 1, p < 0.01) and
      exhibited a significantly higher Modified Health Assessment Questionnaire (MHAQ)
      score (1.13 vs. 0.5, p < 0.01), C-reactive protein (CRP) (1.5 vs. 0.36, p <
      0.01), and disease activity score (DAS) 28-CRP (3.63 vs. 2.81, p < 0.01) compared
      to the controls. CONCLUSIONS: Our study revealed that RA patients requiring
      cervical spine surgery have a higher disease activity (as represented by the
      DAS28-CRP) and are more functionally disabled (as represented by the MHAQ) than
      control patients.

PMID- 24925127
TI  - A novel electrospun biphasic scaffold provides optimal three-dimensional
      topography for in vitro co-culture of airway epithelial and fibroblast cells.
AB  - Conventional airway in vitro models focus upon the function of individual
      structural cells cultured in a two-dimensional monolayer, with limited three
      dimensional (3D) models of the bronchial mucosa. Electrospinning offers an
      attractive method to produce defined, porous 3D matrices for cell culture. To
      investigate the effects of fibre diameter on airway epithelial and fibroblast
      cell growth and functionality, we manipulated the concentration and deposition
      rate of the non-degradable polymer polyethylene terephthalate to create fibres
      with diameters ranging from nanometre to micrometre. The nanofibre scaffold
      closely resembles the basement membrane of the bronchiole mucosal layer, and
      epithelial cells cultured at the air-liquid interface on this scaffold showed
      polarized differentiation. The microfibre scaffold mimics the porous sub-mucosal
      layer of the airway into which lung fibroblast cells showed good penetration.
      Using these defined electrospinning parameters we created a biphasic scaffold
      with 3D topography tailored for optimal growth of both cell types. Epithelial and
      fibroblast cells were co-cultured onto the apical nanofibre phase and the basal
      microfibre phase respectively, with enhanced epithelial barrier formation
      observed upon co-culture. This biphasic scaffold provides a novel 3D in vitro
      platform optimized to mimic the different microenvironments the cells encounter
      in vivo on which to investigate key airway structural cell interactions in airway
      diseases such as asthma. 

PMID- 24925128
TI  - Quantification of left ventricular dyssynchrony in patients with systolic
      dysfunction: a comparison of circumferential strain MR-tagging metrics.
AB  - PURPOSE: To define which circumferential strain MR-tagging metrics of left
      intraventricular dyssynchrony better identifies patients with systolic
      dysfunction against control subjects. MATERIALS AND METHODS: One hundred fifty
      subjects were studied: (i) controls with ejection fraction (EF) > 55% (n = 84),
      (ii) patients with EF <= 55% not eligible for cardiac resynchronization therapy
      (CRT) (n = 52), and (iii) patients eligible for CRT according to the ESC
      guidelines (n = 14). Tagging cine MR-based circumferential filtered strain curves
      were extracted. Six dyssynchrony indices were studied: standard deviation (SD) of
      peak strain (SD_Ecc_ES), SD of time-to-peak (SD_TTP), strain delay index (LIM),
      regional variance vector (RVV), circumferential uniformity ratio estimate (CURE),
      and uniformity of strain TTP (US_TTP). RESULTS: All metrics show significant
      differences between the three groups (ANOVA, P < 10(-4) ) and are correlated with
      EF. Significantly higher AUC values of ROC curves between patients with normal
      vs. decreased EF were obtained with SD_TTP (0.998) and CURE (0.995). Agreement
      among different methods was fair to good (kappa 0.32 to 0.89). Interobserver
      variability was best for CURE (1.2%) and US_TTP (0.8%) while more than 3-times
      larger for other metrics. CONCLUSION: SD_TTP and CURE are the most discriminant
      dyssynchrony metrics for systolic dysfunction. However, taking into account the
      method's variability argues in favor of indices of uniformity of the strain, ie,
      CURE and US_TTP.

PMID- 24925130
TI  - High-accuracy identification of incident HIV-1 infections using a sequence
      clustering based diversity measure.
AB  - Accurate estimates of HIV-1 incidence are essential for monitoring epidemic
      trends and evaluating intervention efforts. However, the long asymptomatic stage
      of HIV-1 infection makes it difficult to effectively distinguish incident
      infections from chronic ones. Current incidence assays based on serology or viral
      sequence diversity are both still lacking in accuracy. In the present work, a
      sequence clustering based diversity (SCBD) assay was devised by utilizing the
      fact that viral sequences derived from each transmitted/founder (T/F) strain tend
      to cluster together at early stage, and that only the intra-cluster diversity is
      correlated with the time since HIV-1 infection. The dot-matrix pairwise alignment
      was used to eliminate the disproportional impact of insertion/deletions (indels)
      and recombination events, and so was the proportion of clusterable sequences (Pc)
      as an index to identify late chronic infections with declined viral genetic
      diversity. Tested on a dataset containing 398 incident and 163 chronic infection
      cases collected from the Los Alamos HIV database (last modified 2/8/2012), our
      SCBD method achieved 99.5% sensitivity and 98.8% specificity, with an overall
      accuracy of 99.3%. Further analysis and evaluation also suggested its performance
      was not affected by host factors such as the viral subtypes and transmission
      routes. The SCBD method demonstrated the potential of sequencing based techniques
      to become useful for identifying incident infections. Its use may be most
      advantageous for settings with low to moderate incidence relative to available
      resources. The online service is available at
      http://www.bioinfo.tsinghua.edu.cn:8080/SCBD/index.jsp. 

PMID- 24925129
TI  - L-type calcium channel modulates cystic kidney phenotype.
AB  - In polycystic kidney disease (PKD), abnormal proliferation and genomic
      instability of renal epithelia have been associated with cyst formation and
      kidney enlargement. We recently showed that L-type calcium channel (CaV1.2) is
      localized to primary cilia of epithelial cells. Previous studies have also shown
      that low intracellular calcium level was associated with the hyperproliferation
      phenotype in the epithelial cells. However, the relationship between calcium
      channel and cystic kidney phenotype is largely unknown. In this study, we
      generated cells with somatic deficient Pkd1 or Pkd2 to examine ciliary CaV1.2
      function via lentiviral knockdown or pharmacological verapamil inhibition.
      Although inhibition of CaV1.2 expression or function did not change division and
      growth patterns in wild-type epithelium, it led to hyperproliferation and
      polyploidy in mutant cells. Lack of CaV1.2 in Pkd mutant cells also decreased the
      intracellular calcium level. This contributed to a decrease in CaM kinase
      activity, which played a significant role in regulating Akt and Erk signaling
      pathways. Consistent with our in vitro results, CaV1.2 knockdown in zebrafish and
      Pkd1 heterozygous mice facilitated the formation of kidney cysts. Larger cysts
      were developed faster in Pkd1 heterozygous mice with CaV1.2 knockdown. Overall,
      our findings emphasized the importance of CaV1.2 expression in kidneys with
      somatic Pkd mutation. We further suggest that CaV1.2 could serve as a modifier
      gene to cystic kidney phenotype. 

PMID- 24925132
TI  - Laboratory preparation of Varicella-Zoster Virus: concentration of virus
      containing supernatant, use of a debris fraction and magnetofection for
      consistent cell-free VZV infections.
AB  - The research laboratory generation of free Varicella-Zoster Virus (VZV) from
      cultured yields results relatively low titers, with the result that most study of
      VZV infection utilizes cell-associated infection. However, important aspects of
      VZV-cell interaction, such as the entry mechanism and superinfection exclusion
      have not yet been studied in detail, in part due to the difficulty in obtaining a
      high titer cell free virus. Here, a method to generate relatively high-titer cell
      free VZV, based on a combination of previously published techniques and
      subsequent concentration is described. VZV-infected cells are disrupted,
      sonicated and clarified by centrifugation. The cell-free virus in the supernatant
      is then concentrated to yield up to 10(5)PFU/ml. The cell debris pellet, which
      contains up to 10(6)PFU/ml can also be used for non cell-associated infection.
      Magnetic nanoparticles available commercially can be used to further enhance
      infection by cell-free-VZV. The tools described here hold promise for better
      understanding of important aspects of VZV-cell interactions such as entry and
      latency. 

PMID- 24925131
TI  - Puberty-related changes in cortisol, dehydroepiandrosterone, and estradiol-17beta
      secretions within the first hour after waking in premenarcheal girls.
AB  - OBJECTIVE: The onset of menstruation is the hallmark of female pubertal
      development. The present study determined whether pubertal girls experience
      adrenocortical and ovarian steroid secretions within their first waking hour
      before getting their period, similar to those observed in adult females with
      regular cycles. METHODS: Cortisol, dehydroepiandrosterone (DHEA), and estradiol
      17beta concentrations were measured in saliva samples collected after awakening
      (0, 30, and 60 min after awakening) from 158 normal premenarcheal pubertal girls
      and 69 adult females with regular menstrual cycles. The girls were subgrouped
      according to self-reported Tanner breast (B) and pubic hair (PH) stages (B1PH1,
      B2PH1, B2PH2, B3PH1, and B3PH2). RESULTS: All the subgroups showed a similar
      pattern of cortisol secretion. However, cortisol levels were higher in girls at
      B3PH1 and at B3PH2 than other subgroups. DHEA secretion showed a similar pattern
      across the groups examined. The largest increase in DHEA levels occurred between
      B1PH1 and B2PH1 stages, and further increased with pubertal progression. DHEA
      levels in girls at B3PH2 were approximately one half of the adult value.
      Estradiol-17beta profiles in girls at B3PH1 and B3PH2 differed from those of
      other subgroups of girl. A sharp increase in estradiol-17beta levels after
      awakening which observed in adult females emerged in girls at B3PH1 and B3PH2.
      However, the estradiol-17beta levels did not reach adult values until B3PH2
      stage. CONCLUSIONS: The progression of female puberty includes an increase in the
      levels of adrenocortical and ovarian steroid secretions and a gain of adult
      female-like patterns of estradiol-17beta secretion within their first waking
      hour.

PMID- 24925133
TI  - New method for the visual detection of human respiratory syncytial virus using
      reverse transcription loop-mediated amplification.
AB  - Human respiratory syncytial virus (HRSV) is a seasonal respiratory pathogen that
      causes respiratory infection in children and the elderly. A new, reverse
      transcriptase loop-mediated isothermal amplification (RT-LAMP) assay was
      developed for the rapid (within 1h), simultaneous detection of A and B group
      HRSV. Primers specific for groups A and B were designed to amplify the N and L
      genes of HRSV, respectively. A fluorescent dye, calcein, was used as an indicator
      for the endpoint visual detection and/or real-time amplification of HRSV RNA. The
      detection limit of the new method was 281.17 50% tissue culture infective doses
      (TCID50)/ml for HRSV A and 1.58 TCID50/ml for HRSV B. To evaluate the validity of
      this method, a comparison with RT-PCR was performed using 77 nasopharyngeal swabs
      as samples. Both RT-LAMP and RT-PCR detected HRSV in 38 HRSV samples, yielding a
      positive rate of 49%. Of the RT-LAMP positive samples, 36 (95%) were also
      positive by RT-PCR, while two were negative by RT-PCR. Among the 36 RT-LAMP and
      RT-PCR positive samples, 11 belonged to HRSV group A, while 25 belonged to group
      B. The results show that the new RT-LAMP is simple, rapid and well suited for
      HRSV diagnosis, especially in a limited-resource setting. 

PMID- 24925134
TI  - Diabetes care may be improved with Steno Quality Assurance Tool--a self
      assessment tool in diabetes management.
AB  - To evaluate if improvements in the quality of diabetes care in Indian clinics can
      be obtained by simple self-surveillance PC-based software. METHOD: Nineteen
      Indian diabetes clinics were introduced to the principles of quality assurance
      (QA), and to a software program, the Steno Quality Assurance Tool (SQAT). Data
      was entered for an initial 3 months period. Subsequently data were analyzed by
      the users, who designed plans to improve indicator status and set goals for the
      upcoming period. A second data entry period followed after 7-9 months. RESULTS:
      QA data was analyzed from 4487 T2DM patients (baseline) and 4440 (follow-up). The
      average examination frequency per clinic of the following indicators increased
      significantly: lipid examination (72-87%) (p=0.007), foot examination (80-94%)
      (p=0.02), HbA1c investigation (59-77%) (p=0.006), and urine albumin excretion
      investigation (72-87%) (p=0.006). Outcome parameters also improved significantly:
      mean (SD) fasting and post prandial BG reduced from 144(16) to 132(16)mg/dl
      (p=0.02) and 212(24)-195(29)mg/dl (p=0.03), respectively. Systolic BP reduced
      from 139(6) to 133(4) (p=0.0008)mmHg and diastolic BP from 83(3) to 81(3)mmHg
      (p=0.002). CONCLUSION: Quality of diabetes care can be improved by applying SQAT,
      a QA self-surveillance software that enables documentation of changes in process
      and outcome indicators.

PMID- 24925136
TI  - Stability analysis for discrete-time switched systems with unstable subsystems by
      a mode-dependent average dwell time approach.
AB  - This paper mainly intends to present new stability results of a discrete-time
      switched system with unstable subsystems. By adopting multiple Lyapunov
      functions' (MLFs') method, new and less conservative stability conditions are
      derived in terms of a set of numerical feasible linear matrix inequalities (LMIs)
      with mode-dependent average dwell time (MDADT) techniques. Different from
      previous literatures, unstable subsystems are considered under two situations in
      this paper. It is shown that the discrete-time switched system can achieve
      exponential stability under a slow switching scheme and even in the presence of
      fast switching of unstable subsystems. Finally a numerical example is given to
      demonstrate the effectiveness of the proposed method. 

PMID- 24925135
TI  - Screening strategies for thyroid disorders in the first and second trimester of
      pregnancy in China.
AB  - BACKGROUND: Thyroid dysfunction during pregnancy is associated with multiple
      adverse outcomes, but whether all women should be screened for thyroid disorders
      during pregnancy remains controversial. OBJECTIVE: To evaluate the effectiveness
      of the targeted high risk case-finding approach for identifying women with
      thyroid dysfunction during the first and second trimesters of pregnancy. METHODS:
      Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid
      peroxidase antibodies (TPOAb) were measured in 3882 Chinese women during the
      first and second trimester of pregnancy. All tested women were divided into the
      high risk or non-high risk groups, based on their history, findings from physical
      examination, or other clinical features suggestive of a thyroid disorder.
      Diagnosis of thyroid disorders was made according to the standard trimester
      specific reference intervals. The prevalence of thyroid disorders in each group
      was determined, and the feasibility of a screening approach focusing exclusively
      on high risk women was evaluated to estimate the ability of finding women with
      thyroid dysfunction. RESULTS: The prevalence of overt hypothyroidism or
      hyperthyroidism in the high risk group was higher than in the non-high risk group
      during the first trimester (0.8% vs 0, chi2 = 7.10, p = 0.008; 1.6% vs 0.2%, chi2
      = 7.02, p = 0.008, respectively). The prevalence of hypothyroxinemia or TPOAb
      positivity was significantly higher in the high risk group than in the non-high
      risk group during the second trimester (1.3% vs 0.5%, chi2 = 4.49, p = 0.034;
      11.6% vs 8.4%, chi2 = 6.396, p = 0.011, respectively). The total prevalence of
      hypothyroidism or hyperthyroidism and the prevalence of subclinical
      hypothyroidism or hyperthyroidism were not statistically different between the
      high risk and non-high risk groups, for either the first or second trimester.
      CONCLUSION: The high risk screening strategy failed to detect the majority of
      pregnant women with thyroid disorders. Therefore, we recommend universal
      screening of sTSH, FT4, and TPOAb during the first trimester and second trimester
      of pregnancy.

PMID- 24925137
TI  - Amniotic fluid embolism induces uterine anaphylaxis and atony following cervical
      laceration.
AB  - Amniotic fluid embolism (AFE) is a rare, high-risk obstetric complication
      primarily found in the lungs and potentially related to anaphylaxis. Tryptase
      release from the mast cell reflects anaphylaxis. Case report and findings: A
      female, aged over 40 years, presented with uterine atony and lethal hemorrhage
      after induced vaginal labor. Cervical laceration was accompanied by severe
      hemorrhage. Stromal edema and myometrial swelling were consistent with uterine
      atony. Alcian blue staining and zinc coproporphyrin immunostaining disclosed AFE,
      which was more prominent in the uterus than in the lungs. Tryptase immunostaining
      was diffuse and prominent around the activated mast cells (halos) in the uterus,
      including the cervix. Similar distribution of findings on the AFE markers,
      tryptase halos, complement receptor C5aR, and atony in the uterus suggested the
      causality of AFE to anaphylaxis, complement activation and atony. It is probable
      that disseminated intravascular coagulation (DIC), induced by AFE, uterine atony
      and cervical laceration, caused the lethal hemorrhage. It is likely that AFE, in
      association with cervical laceration, induces uterine anaphylaxis, complement
      activation, atony, DIC and lethal hemorrhage.

PMID- 24925138
TI  - The endocrine society diabetes and pregnancy guidelines: a critical appraisal.

PMID- 24925140
TI  - Immunometabolism: a beige immune response.

PMID- 24925139
TI  - From empiricism to rational design: a personal perspective of the evolution of
      vaccine development.
AB  - Vaccination, which is the most effective medical intervention that has ever been
      introduced, originated from the observation that individuals who survived a
      plague or smallpox would not get the disease twice. To mimic the protective
      effects of natural infection, Jenner - and later Pasteur - inoculated individuals
      with attenuated or killed disease-causing agents. This empirical approach
      inspired a century of vaccine development and the effective prophylaxis of many
      infectious diseases. From the 1980s, several waves of new technologies have
      enabled the development of novel vaccines that would not have been possible using
      the empirical approach. The technological revolution in the field of vaccination
      is now continuing, and it is delivering novel and safer vaccines. In this
      Timeline article, we provide our views on the transition from empiricism to
      rational vaccine design.

PMID- 24925141
TI  - Morphology and ciliary motion of mucosa in the Eustachian tube of neonatal and
      adult gerbils.
AB  - The Eustachian tube is a small canal that connects the tympanic cavity with the
      nasal part of the pharynx. The epithelial lining of the Eustachian tube contains
      a ciliated columnar epithelium at the tympanic cavity and a pseudostratified,
      ciliated columnar epithelium with goblet cells near the pharynx. The tube serves
      to equalize air pressure across the eardrum and drains mucus away from the middle
      ear into the nasopharynx. Blockage of the Eustachian tube is the most common
      cause of all forms of otitis media, which is common in children. In the present
      study, we examined the epithelial lining of the Eustachian tube in neonatal and
      adult gerbils, with a focus on the morphological and functional development of
      ciliated cells in the mucosa. The length of the tube is ~8.8 mm in adult gerbils.
      Scanning electron microscopy showed that the mucosal member near the pharyngeal
      side contains a higher density of ciliated cells and goblet cells than that near
      the tympanic side. The cilia beat frequency is 11 Hz. During development, the
      length of the Eustachian tube increased significantly between postnatal day 1
      (P1) and P18. Scanning electron microscopy showed that the mucosa contained a
      high density of ciliated cells with a few goblet cells at P1. The density of
      ciliated cells decreased while the density of goblet cells increased during
      development. At P18, the mucosa appeared to be adult-like. Interestingly, the
      ciliary beat frequency measured from ciliated cells at P1 was not statistically
      different from that measured from adult animals. Our study suggests that the
      Eustachian tube undergoes significant anatomical and histological changes between
      P1 and P18. The tube is morphologically and functionally mature at P18, when the
      auditory function (sensitivity and frequency selectivity) is mature in this
      species. 

PMID- 24925142
TI  - Knot Strength Varies Widely Among Expert Arthroscopists.
AB  - BACKGROUND: While most surgeons can tie visually appealing knots under an
      arthroscope, few surgeons have undergone an objective evaluation of their ability
      to consistently tie knots with maximum loop and knot security.
      PURPOSE/HYPOTHESES: The purpose of this study was to evaluate and compare
      variations in ultimate load to failure, 3-mm displacement (clinical failure), and
      knot stack height of arthroscopic suture knots tied by 73 independent expert
      orthopaedic arthroscopists. The hypotheses were (1) that skilled arthroscopic
      surgeons would be able to routinely tie arthroscopic knots of similar strength,
      (2) that surgeons with <10 years of clinical practice would tie stronger and more
      consistent knots, and (3) that surgeons who performed >200 arthroscopic shoulder
      cases per year would produce stronger and more consistent knots than would
      surgeons who performed fewer cases. STUDY DESIGN: Controlled laboratory study.
      METHODS: Each surgeon tied 5 of the same type of their preferred arthroscopic
      knot and half-hitch locking mechanism. Each knot was mechanically tested for
      ultimate load to failure and clinical failure. RESULTS: For the 365 individual
      knots tested, the mean ultimate load across each knot was 231 N (range, 29-360
      N). The mean clinical failure load was 139 N (range, 16-328 N). The average knot
      stack height among the 365 knots was 5.61 mm (range, 2.89-10.32 mm). For an
      individual surgeon, the standard deviations of the 5 consecutive knots tied
      ranged from 6 to 133 N. The ultimate load and clinical failure load for surgeons
      with <10 years of practice (n = 39) were 248 +/- 93 N and 142 +/- 56 N,
      respectively. The mean +/- SD ultimate and clinical failure loads for surgeons
      with >10 years of practice (n = 34) were 211 +/- 111 N and 136 +/- 69 N,
      respectively. When knot strength was used to measure performance, significant
      differences existed in ultimate load (P = .001); however, there were no
      differences in clinical failure load (P = .329). Surgeons with <10 years of
      practice were able to tie knots more consistently than were surgeons in practice
      for >10 years, for both ultimate load (P = .018) and clinical failure load (P =
      .005). There was no significant difference based on number of cases performed
      with respect to ultimate load or clinical failure load (P = .292 and .479,
      respectively). There was no difference in consistency, as both groups had similar
      standard deviations (P = .814 for ultimate load, P = .545 for clinical failure).
      CONCLUSION: Considerable variations in knot strength exist between arthroscopic
      knots tied by surgeons. Study findings revealed that surgeons were unable to tie
      5 consecutive knots of the same type consistently; that for both ultimate load
      and clinical failure load, surgeons with <10 years in practice were able to tie
      knots more consistently than surgeons with >10 years; and that surgeons
      performing >200 arthroscopic shoulder cases annually failed to tie stronger or
      more consistent knots than their counterparts performing fewer cases. CLINICAL
      RELEVANCE: This variation in knot tying has the potential to affect the integrity
      of arthroscopic repairs. Independent objective testing of the ability to tie
      secure knots as part of a surgeons' training may be necessary.

PMID- 24925143
TI  - Factors influencing graft impingement on the wall of the intercondylar notch
      after anatomic double-bundle anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Anatomic placement of the bone tunnel reportedly reduces impingement
      of the graft with the intercondylar roof, but as a trade-off, the risk of
      impingement with the lateral wall of the intercondylar notch would increase
      instead in anatomic double-bundle anterior cruciate ligament (ACL)
      reconstruction. PURPOSE: The 2 grafts for the anteromedial bundle (AMB) and
      posterolateral bundle (PLB) were separately analyzed for the frequency of and
      risk factors for graft impingement on the wall of the intercondylar notch. STUDY
      DESIGN: Case control study; Level of evidence, 3. METHODS: A total of 51 patients
      (53 knees) who underwent primary anatomic double-bundle ACL reconstruction were
      enrolled. Based on the graft orientation plane reconstructed with 3-dimensional
      imaging software, graft-wall impingement was defined as overlap between the
      lateral wall of the notch and the line connecting each center of the intra
      articular apertures of the femoral and tibial bone tunnels. The rate of wall
      impingement was assessed for each bundle. Parameters for bone tunnel positioning
      in the femur and tibia, notch width index, and knee joint rotation angle were
      compared between patients with and without wall impingement. The most important
      risk factors for wall impingement were assessed by logistic regression analysis.
      RESULTS: Wall impingement for the AMB was observed in 22 knees (42%), whereas no
      patients exhibited wall impingement for the PLB. Regarding femoral bone tunnel
      positioning according to the quadrant method, the AMB bone tunnel was placed
      significantly higher in impingement-positive patients than in impingement
      negative patients (P = .03). Regarding tibial tunnel positioning, the tunnel was
      placed significantly more anteriorly (P = .02) and laterally (P = .02) in the
      impingement-positive group than in the impingement-negative group. Bone tunnels
      positioned 48% to 50% from the medial border of the tibia demonstrated a 100%
      incidence of wall impingement. Based on logistic regression analysis, lateral
      deviation of the AMB tibial bone tunnel was significantly associated with wall
      impingement (odds ratio, 1.403; P = .048). CONCLUSION: The tibial bone tunnel
      position in the coronal orientation was most likely associated with wall
      impingement. Considering that tibial bone tunnels are generally created with the
      knee in 90 degrees  of flexion and move laterally as the knee extends because of
      screw-home movement, the AMB bone tunnel for the tibia should be positioned as
      medially as possible within its footprint to minimize the risk of wall
      impingement after anatomic double-bundle ACL reconstruction.

PMID- 24925144
TI  - Pulmonary mucormycosis due to Lichtheimia ramosa in a patient with HIV infection.
AB  - Mucormycosis is increasingly common in patients with risk factors such as
      diabetes mellitus, neutropenia, and corticosteroid therapy. However, mucormycosis
      seems to be less common in patients with human immunodeficiency virus (HIV)
      infection compared to patients with other risk factors. Despite their lower
      virulence, Lichtheimia species should be regarded as emerging pathogens among
      Mucoralean fungi. We report a fatal case of pulmonary mucormycosis due to
      Lichtheimia ramosa in a 52-year-old man with an end-stage HIV infection. He had a
      cachectic appearance and his CD4 count was 8 cells/mm(3). The fungal infection
      was diagnosed based on a positive sputum culture with histopathologic
      confirmation. The fungus was resistant to caspofungin, anidulafungin, and
      voriconazole [minimum inhibitory concentration (MCI) >32 ug/ml], whereas the E
      test MIC values of itraconazole, posaconazole, and amphotericin B were 0.38,
      0.38, and 0.5 ug/ml, respectively. Although intravenous drug use is the main risk
      factor for the development of mucormycosis in HIV-infected patients, it may also
      develop in patients with low CD4 count, opportunistic infections and/or
      additional diseases, such as Kaposi's sarcoma or severe immunodeficiency, as in
      our case.

PMID- 24925145
TI  - Predictive value of CMR criteria for LV functional improvement in patients with
      acute myocarditis.
AB  - AIM: We assessed the value of cardiovascular magnetic resonance (CMR) criteria
      ('Lake Louise Criteria') for predicting left ventricular (LV) functional
      improvement in patients with acute myocarditis. METHODS AND RESULTS: We studied
      37 patients who referred for acute myocarditis during clinically acute
      myocarditis and after a 12-month follow-up. CMR sequences sensitive for oedema,
      hyperaemia, and irreversible injury were applied. Global and regional oedema were
      defined using published quantitative signal intensity (SI) cut-off values (area
      with an SI of >2 SD above visually normal myocardium). LV function was analysed
      using six long-axis views, with an increase of at least 5% of left ventricular
      ejection fraction considered as improvement. Out of a total of 37 patients, 29
      met the CMR Lake Louise criteria (LL+) and eight did not (LL-). Baseline and 12
      month ejection fraction (EF) were significantly lower in LL+ (53.2 +/- 8 vs. 62.2
      +/- 5, P = 0.007 and 58.9 +/- 4 vs. 62.9 +/- 5, P = 0.045, respectively). At
      follow-up, EF increased in LL+ but remained unchanged within normal limits in LL-
      groups (delta EF: 5.7 +/- 9.8 vs. 0.7 +/- 2.0). The presence of global or
      regional myocardial oedema was strongly associated with an increase of EF >=5%.
      In a multivariate analysis, the presence of global and/or regional oedema on
      admission was the only independent predictor of an increase of EF (P = 0.046).
      CONCLUSION: In patients with clinically suspected acute myocarditis, the presence
      of positive CMR criteria is associated with LV function recovery. Myocardial
      oedema as defined by CMR was the strongest parameter, indicating that the
      observed increase of EF may be due to the recovery of reversibly injured
      (oedematous) myocardium.

PMID- 24925146
TI  - Importance of visualization the myocardium at risk in myocardial infarction.

PMID- 24925147
TI  - Prevalence of uninvestigated dyspepsia and gastroesophageal reflux disease in
      Korea: a population-based study using the Rome III criteria.
AB  - BACKGROUND/AIMS: There have been few population-based studies on the prevalences
      of gastroesophageal reflux disease (GERD) and dyspepsia using Rome III criteria
      in Asian countries. METHODS: A population-based, cross-sectional study was
      conducted by telephone interviews of 5,000 Koreans between the ages of 20-69
      years. Gastrointestinal symptoms were assessed by a translated Korean version of
      Rome III criteria. Uninvestigated dyspepsia (UID) was defined by symptom criteria
      of Rome III. GERD was defined by troublesome heartburn and/or acid regurgitation
      occurring at least once a week. The EQ5D assessment tool was used for the
      evaluation of quality of life. RESULTS: The prevalences of UID, postprandial
      distress syndrome (PDS), and epigastric pain syndrome (EPS) were 7.7, 5.6, and
      4.2 %, respectively. Overlap between PDS and EPS was found in 27.1 % (104/384) of
      subjects with UID. There were no significant differences in demographic variables
      between patients with PDS and EPS. The prevalence of GERD was 7.1 %. Overlap
      between GERD and UID was found in 50.0 % of GERD patients. The EQ5D index of
      patients without either UID or GERD was 0.92 +/- 0.07, and those of patients with
      only UID, with only GERD, and with both UID and GERD were 0.88 +/- 0.09, 0.88 +/-
      0.11, and 0.84 +/- 0.15, respectively. CONCLUSIONS: GERD and UID based on Rome
      III criteria were prevalent and significantly affected the quality of life in
      Korea. In Korean patients with UID, there was considerable overlap and there were
      no significant differences in demographic variables between PDS and EPS.

PMID- 24925149
TI  - An unusual cause of recurrent right lower quadrant pain.

PMID- 24925150
TI  - GRG update: DDW 2014.

PMID- 24925148
TI  - Advanced colorectal adenomas in patients under 45 years of age are mostly
      sporadic.
AB  - BACKGROUND: The presence of advanced adenomas in younger individuals is a
      criterion for Lynch syndrome (LS). However, the utility of screening advanced
      adenomas for loss of mismatch repair (MMR) protein expression to identify
      suspected LS remains unclear. AIMS: Determine the prevalence of MMR defects to
      understand whether these patients harbor a defined genetic risk for CRC. METHODS:
      The study cohort included adult patients <=45 years of age with advanced adenomas
      (villous histology, >=1 cm in diameter, >=3 polyps of any size) endoscopically
      removed between 2001 and 2011. Clinical records were reviewed along with detailed
      pathological review and immunohistochemical MMR analysis. RESULTS: A total of 76
      (40.1 % male, age 40.6 +/- 5.4 years) patients met inclusion and exclusion
      criteria. Indications for colonoscopy were gastrointestinal (GI) bleeding 39
      (51.3 %), CRC in a first-degree relative 17 (22.4 %) and somatic GI symptoms 20
      (26.3 %). Index colonoscopy revealed a median of 1 adenoma (range 1-4), mean
      diameter of 12.9 +/- 7.1 mm, 40 (52.6 %) with villous histology. The mean follow
      up duration was 3.3 +/- 2 years. Recurrent adenomas developed in 24 (31.6 %), of
      which 8 (10.5 %) were advanced adenomas; none of these patients developed CRC.
      One of 66 (1.5 %) adenomas available for immunohistochemical (IHC) testing
      revealed loss of MLH1 and PMS2. CONCLUSIONS: IHC screening of advanced adenomas
      from patients younger than 45 years of age identified potential LS in one of 64
      patients. The low yield of IHC screening in this population suggests that
      universal IHC screening of advanced adenomas from patients younger than 45 years
      of age for MMR defects is not an efficient strategy for identifying LS subjects.

PMID- 24925151
TI  - Target cell extraction coupled with LC-MS/MS analysis for screening potential
      bioactive components in Ginkgo biloba extract with preventive effect against
      diabetic nephropathy.
AB  - A rapid and useful approach for screening potential bioactive components in
      Ginkgo biloba extract (GBE) with preventive effect against diabetic nephropathy
      (DN) was developed using mesangial cells extraction coupled with high-performance
      liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Mesangial
      cells were first divided into two groups according to their treatments with high
      glucose or high glucose plus GBE. After incubation for 4, 8, 12, 16, 24 and 48 h,
      the cells were harvested and extracted with 40% acetic acid in water before LC
      MS/MS analysis. Then, 19 compounds and five metabolites were found to selectively
      combine with mesangial cells. Notably, compounds including quercetin and rutin
      were identified or tentatively characterized according to the results of
      retention time and MS spectra, which is highly consistent with our previous
      reports that quercetin and rutin are potent protective agents against
      glomerulosclerosis in DN. Therefore, all these results indicate that target cell
      extraction coupled with LC-MS/MS analysis can be successfully applied for
      predicting the bioactive components in GBE with preventive effect against DN.

PMID- 24925152
TI  - Genetics of common malformations.
AB  - Advanced technology has recently allowed us to study rare Mendelian disorders in
      an unprecedented manner. The same technology should allow us also to study more
      common malformations. Many of these are not caused by a variant in a single
      Mendelian gene but by interplay between series of genetic variants and exogenous
      influences. Likely the site from which the DNA is derived is of great importance
      in studying malformations as mosaicism may be much more common than earlier
      anticipated. Factors other than simple variants in our genomic DNA should be
      considered in the studies as well. Not only is recognition of someone's liability
      to disease important, but also determining exogenous factors involved in
      malformations should receive more attention as it may allow us decrease the
      burden of malformations in humans. 

PMID- 24925154
TI  - The development of differences in the feeding behaviour of bottle and breast fed
      human infants from birth to two months.
AB  - An entire feeding session is videotaped at monthly intervals starting shortly
      after birth for a group of bottle and breast-fed infants. Mothers keep daily
      diaries of infants' activity and meal patterns. Several differences are apparent
      in the form of feeding sequence which appear characteristic of the technique.
      Bottle feeds are more mother-controlled in that breaks in the feed sequence are
      almost entirely mother initiated whereas with breast-fed infants the baby is more
      in control. Over the first 2 months differences appear in the size of meals with
      breast-fed infants showing a marked diurnal rhythm which is absent in the bottle
      fed infant. These findings are discussed in relation to problems of obesity and
      of health education. 

PMID- 24925153
TI  - Advances in the management of low-grade gliomas.
AB  - Low-grade gliomas (LGGs) represent the most common childhood brain tumors and are
      a histologically heterogenous group of tumors. Most LGGs are surgically
      resectable with excellent 10-year overall survival outcomes of more than 90 %
      with surgery alone. Tumors not amenable to surgical resection and those with an
      aggressive biology are more challenging to treat. Conventional radiotherapy is a
      more efficacious method of long-term tumor control than chemotherapy. However,
      radiation is associated with significant cognitive, endocrine, and
      cerebrovascular late effects, making chemotherapy an often-preferred modality
      over radiotherapy, especially in younger children. Multiple chemotherapy regimens
      have been evaluated over the past few decades with comparable survival outcomes
      and differing toxicity profiles. Newer regimens containing antiangiogenic agents
      also show promise. Recent molecular studies have implicated the BRAF oncogene, a
      key regulator of the MAPK pathway, and the AKT/mTOR pathway in pediatric LGG
      tumorigenesis. This has opened up promising new avenues for targeted therapy,
      with many agents currently under investigation.

PMID- 24925155
TI  - Parturition in the rat (Rattus norvegicus): Normative aspects and the temporal
      patterning of behaviours.
AB  - The purpose of this paper was to present a quantitative analysis of parturition
      in the laboratory rat. In addition, the effects of parity were also investigated.
      Gestational length was 22-23 days (day sperm found was Day 1) in 95% of the
      pregnancies. The average length of parturition was 97.3 min. The mean litter size
      was 10.84 pups and the average weight of each pup at birth was 6.49g. The effects
      of parity were limited to changes in two parturitional behaviours: Mount and
      Lordosis Contraction. These changes may reflect the conditioning of the uterus in
      response to a prior pregnancy. Pub births and placental expulsions did not occur
      at equidistant points throughout parturition. Following the birth of the first
      pup there was a characteristic lull in births. Indeed, almost two-thirds of the
      births occurred during the second half of parturition. The expulsion of placentas
      followed a similar time course though displaced to the right, reflecting the fact
      that placentas are expelled at some point following the birth of a pup. The main
      thrust of this paper was the temporal sequencing of parturitional behaviours. The
      21 behaviours clustered into five phases which were defined in terms of their
      peak occurrence during parturition. The first phase - the Initiation Phase - was
      consonant with the birth of the first pup. During parturition, the female spent
      much of her time licking the first born, grooming her head, and sniffing in
      response to the novelty of the birth fluids. The second phase - the Contraction
      Phase - was marked by a lul in the pup births. During this phase the predominant
      contraction pattern shifted from Lordosis, the type of contraction seen prior to
      the birth of the first pup, to the transitional type (Intermediate) and finally
      to the Vertical Contraction. It was the Vertical Contraction which was closely
      associated with the birth of pups. The third phase - the Birth-Oriented Phase -
      included the second half of parturition, when the majority of the litter was
      born. The behaviours exhibited during this phase were intricately involved with
      pup births per se. The female spent much time grooming and pulling at the
      anogenital region, eating placentas, and grooming herself to clean the copious
      quantities of birth fluids. The fourth phase - the Termination Phase - was marked
      by the birth of the last pup in the litter. Sniff Pup reached its highest levels
      during this phase. The fifth phase - the Nursing Phase - began after all the pups
      had been born, cleaned, stimulated, and clustered. The female then became
      quiescent over the young and nursing was initiated. A sixth cluster of behaviours
      exhibited low levels of occurrence and the absence of temporal patterning. Thus,
      parturition in the rat is characterized by an orderly progression of behaviours
      through the parturitional period. In addition, several naturally occurring
      behaviours such as Groom Dorsal and Eat-Drink are maintained at very low levels
      throughout the delivery. 

PMID- 24925156
TI  - The response of willow grouse chicks to auditory stimuli 3. Recognition of the
      incubating hen's voice.
AB  - Willow grouse chicks were removed from the nests of captive hens, either at
      hatching or less than 24 hours later. They were tested for their ability to
      discriminate, and preference for, the voice of the hen which had incubated them,
      and the voice of another hen grouse. The chicks removed at hatching approached
      and tried to nestle under the loudspeaker playing the calls of their own hens.
      The chicks which had remained with their hens and been brooded by them were
      indifferent to the recording of their voices, but tended to avoid the voice of
      the unknown hen. 

PMID- 24925157
TI  - The effect of size and hormonal state on the establishment of dominance in young
      males of Tilapia mariae (Pisces: Cichlidae).
AB  - Pairs of young males of Tilapia mariae were allowed to establish dominance in an
      aquarium large enough for one territory only. The fishes differed in size and/or
      in the androgenic hormonal state, which was measured by the size of the male
      genital papilla. The fish with a larger papilla won most of the encounters.
      Overall size was decisive for winning only if the genital papillae sizes of the
      contestants were equal, or if the differences between the genital papillae were
      small, but there was a large overall size difference. It is concluded that in
      these encounters dominance is assessed mostly by asymmetries in pay-offs (state
      of reproductive readiness) and not by asymmetries in resource holding potentials
      (size). 

PMID- 24925158
TI  - The responses of ventral cord neurons of Decticus verrucivorus (L) to sound and
      vibration stimuli.
AB  - The real time analysis of the song of D. verrucivorus recorded in the sun and
      shade shows that changes occur predominantly in the time parameters and not in
      the frequency content. Single unit recordings in the ventral nerve cord of D.
      verrucivorus show that all the acoustic units respond to both sound and
      vibration. However, on the basis of their response characteristics they may be
      classified as vibration (V), vibration and sound (VS) and sound (S) neurons. The
      responses of some of the units depend upon the degree of habituation. Single
      parameter processing was not observed; the characteristic frequencies of these
      units range across the whole of the frequency band investigated, and distinct
      intensity response fields were observed. Some of the V neurons were more
      sensitive than the receptors, and some units responded well to the species song
      when both sound and vibration were presented simultaneously. The source of the
      vibratory input is shown to be predominantly from the ipsilateral foreleg. Many
      of the units run together in an 'acoustic bundle'; some run through fibres,
      passing from the posterior thoracic ganglia to the cervical connectives. In many
      cases the primary fibres projecting to these central units can be predicted from
      their response characteristics. An hypothesis of the mechanisms underlying
      conspecific song recognition at the ventral cord level is presented. 

PMID- 24925159
TI  - Behaviour of the Indian desert gerbil, Meriones hurrianae (Jerdon), during
      recovery from food and water deprivation.
AB  - The responses of Meriones hurrianae deprived of food and food-cum-water were
      found to be similar in respect of time spent in feeding, exploration and drinking
      whereas water- deprived gerbils fed for a significantly (P < 0.01) shorter time.
      However, they explored twice (P < 0.01) as long as gerbils in the other two
      conditions of deprivation. These observations indicate that deprivation of water
      increases exploratory behaviour among M. hurrianae but food, and food-cum-water
      deprivation do not seem to influence it. The behaviour of M. hurrianae, when
      deprived of water, mostly alternated between exploration and drinking whereas
      feeding was the major behavioural component of the gerbils deprived of food, and
      food-cum-water. It appears that feeding behaviour among M. hurrianae is of a
      higher order than drinking behaviour since the animals depend chiefly on the
      available water content of the food in their natural invironment - the desert. 

PMID- 24925165
TI  - Impact of probing the reproductive tract during early pregnancy on fertility of
      beef cows.
AB  - This short communication reports the impact of endometrial biopsies, uterine
      flushings and follicular fluid aspiration procedures at day 6 post artificial
      insemination (AI) on pregnancy rates. In Experiment 1, cows were timed AI (TAI)
      and assigned to the following treatment groups: control (n = 37), uterine
      flushing (n = 35) and endometrial biopsy (n = 38). On day 30 post AI, pregnancy
      rates were 40.5%, 33% and 28.5%, respectively (p > 0.1). Pregnancy rate on day 60
      was lower (p < 0.004) in flushed cows than in the controls. In Experiment 2,
      oestrus was detected and cows were assigned to flushing (n = 32) or biopsy (n =
      33) treatments 6 days after AI, which resulted in pregnancy rates of 31% and 36%,
      respectively (p > 0.1). In Experiment 3, cows were, 6 days after TAI, randomly
      assigned to the following treatments: control (n = 84) or aspiration of the
      largest follicle (n = 73). Pregnancy rates on day 30 post AI were 63.5% for the
      control group and 53% for the aspirated group (p > 0.1). In conclusion, uterine
      flushing and endometrial biopsy negatively affect pregnancy rates, but neither
      procedure can be considered to be incompatible with pregnancy maintenance.
      Follicular aspiration during pregnancy does not interact with pregnancy success.
      The amount and quality of samples obtained are compatible with the use of
      cellular and molecular analysis of uterine variables from cows that failed or
      succeeded on maintaining pregnancy.

PMID- 24925166
TI  - Direct synthesis of Fe3 C-functionalized graphene by high temperature autoclave
      pyrolysis for oxygen reduction.
AB  - We present a novel approach to direct fabrication of few-layer graphene sheets
      with encapsulated Fe3 C nanoparticles from pyrolysis of volatile non-graphitic
      precursors without any substrate. This one-step autoclave approach is facile and
      potentially scalable for production. Tested as an electrocatalyst, the graphene
      based composite exhibited excellent catalytic activity towards the oxygen
      reduction reaction in alkaline solution with an onset potential of ca. 1.05 V
      (vs. the reversible hydrogen electrode) and a half-wave potential of 0.83 V,
      which is comparable to the commercial Pt/C catalyst.

PMID- 24925167
TI  - Role of emergency ureteroscopy in the management of ureteric stones: analysis of
      394 cases.
AB  - OBJECTIVE: To analyse the outcomes of emergency ureteroscopy (URS) cases
      performed in Auckland City Hospital. METHODS: We conducted a retrospective review
      of all emergency URS procedures performed at Auckland City Hospital between 1
      January 2010 and 31 December 2011. Data on patients, stones and procedures were
      collected and analysed. Emergency URS failure was defined as fragments >3 mm or
      the need for a repeat procedure. RESULTS: A total of 499 URS procedures were
      identified. Of these 394 (79%) were emergency procedures. The mean (sd; range)
      patient age was 48 (16; 13-88) years. In all, 83% of emergency URS cases had an
      American Society of Anesthesiologists (ASA) score of 1 or 2, 25% of stones were
      >9 mm, with a mean (sd) size of 8 (4) mm, and 285 procedures (72%) were
      successful. These patients were younger (47 vs 51 years), were more likely to
      have an ASA score of 1 (103 patients in the successful treatment group vs 26 in
      the failed treatment group), had smaller stones (7 vs 9 mm) and were more likely
      to have distal stones (P < 0.05). A total of 20 complications (5%) were recorded
      including six false passages and three mucosal injuries, one of which required
      radiological intervention, and 50 patients (13%) re-presented, for pain (76%),
      bleeding (10%) or infection (14%). CONCLUSION: We showed that emergency URS is a
      feasible approach for the routine management of acute ureteric colic with a low
      complications rate. A subgroup of younger, healthier patients may benefit the
      most from the procedure.

PMID- 24925168
TI  - Hypertriglyceridemia and pancreatitis in a patient with apolipoprotein E7
      (p.[E244K; E245K])/E4.
AB  - BACKGROUND: The etiology of hypertriglyceridemia is complex and one of the common
      variants in affecting plasma lipid levels is apolipoprotein (apo) E isoform.
      Scores of apo E variants have been reported, including apo E7. However, a
      clinical lipid phenotype of apo E7 has not been fully elucidated. METHODS: A 48
      year-old Japanese male had hypertriglyceridemia and a history of repeated
      episodes of acute pancreatitis. The measurement of serum apolipoproteins and apo
      E phenotyping, and the sequencing analyses of several genes regulating
      triglyceride metabolism were performed in the patient. RESULTS: The apo E
      phenotype of the patient was E7/E4. Apo E7 had the same point mutations p.[E244K;
      E245K] in APOE as reported previously. In addition, he had APOA5 haplotypes
      associated with hypertriglyceridemia. Laboratory examinations excluded deficiency
      of apolipoproteins, lipoprotein lipase, and GPI-HBP1 in this patient.
      CONCLUSIONS: This is, to our knowledge, the first report of severe
      hypertriglyceridemia and acute pancreatitis in a patient with apo E7.

PMID- 24925169
TI  - Advances in anti-epileptic drug testing.
AB  - In the past twenty-one years, 17 new antiepileptic drugs have been approved for
      use in the United States and/or Europe. These drugs are clobazam, ezogabine
      (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide,
      lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide,
      stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug
      monitoring is often used in the clinical dosing of the newer anti-epileptic
      drugs. The drugs with the best justifications for drug monitoring are
      lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide.
      Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and
      are candidates for monitoring of the free drug fractions. Alternative specimens
      for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic
      drug monitoring of the new antiepileptic drugs is discussed here for managing
      patients with epilepsy. 

PMID- 24925170
TI  - The keyboard instruments.
AB  - Now that the field of performing arts medicine has been in existence for over
      three decades, we are approaching a key point: we should start to see more
      articles that bring together the data that have been collected from several
      studies in order to draw more robust conclusions. Review articles and their more
      structured relative, the meta-analysis, can help to improve our understanding of
      a particular topic, comparing and synthesizing the results of previous research
      that has been done on that subject area. One way this could be done would be to
      review the research that has been carried out on the performance-related problems
      associated with playing a particular instrument or group of instruments. While I
      am not going to do that myself, I hope that others will. In this editorial, I
      will do a very selective review of the playing-related musculoskeletal disorders
      (PRMDs) associated with one instrument group (the keyboard instruments), focusing
      on the most played instrument in that group (the piano;).

PMID- 24925171
TI  - Benefits of music training are widespread and lifelong: a bibliographic review of
      their non-musical effects.
AB  - Recent publications indicate that musical training has effects on non-musical
      activities, some of which are lifelong. This study reviews recent publications
      collected from the Performing Arts Medicine Association bibliography. Music
      training, whether instrumental or vocal, produces beneficial and long-lasting
      changes in brain anatomy and function. Anatomic changes occur in brain areas
      devoted to hearing, speech, hand movements, and coordination between both sides
      of the brain. Functional benefits include improved sound processing and motor
      skills, especially in the upper extremities. Training benefits extend beyond
      music skills, resulting in higher IQs and school grades, greater specialized
      sensory and auditory memory/recall, better language memory and processing,
      heightened bilateral hand motor functioning, and improved integration and
      synchronization of sensory and motor functions. These changes last long after
      music training ends and can minimize or prevent age-related loss of brain cells
      and some mental functions. Early institution of music training and prolonged
      duration of training both appear to contribute to these positive changes.

PMID- 24925172
TI  - Musculoskeletal pain among Polish music school students.
AB  - OBJECTIVE: To assess the prevalence and intensity of musculoskeletal pain and to
      estimate probability of developing playing-related musculoskeletal disorders,
      depending on risk factors, including gender, years of playing the musical
      instrument, frequency of practice (number of days per week), average daily
      practice time, and habitual physical activity level, in young instrumentalists.
      METHODS: A total of 225 instrumentalists aged 10-18 years, including 107 string
      players, 64 keyboardists, and 54 wind-players, were investigated. The Nordic
      Musculoskeletal Questionnaire (NMQ) together with a numerical visual-analogue
      pain intensity scale (VAS) was used to assess the participants' musculoskeletal
      pain. RESULTS: The young instrumentalists most often complained of pain located
      in the neck (60.4%), wrists (44.4%), and upper (41.7%) and lower back (38.2%)
      areas. Girls complained of musculoskeletal pain significantly more often than the
      boys. A probability of the pain symptoms was increased with each consecutive year
      of practice (OR 1.135; 95%CI 1.021-1.261). CONCLUSIONS: Musculoskeletal pain in
      various body parts had already commenced at a young age in our sample of music
      students, and there was a gender difference (girls were more often affected).
      Results of our study suggest that an early prophylaxis of playing-related
      musculoskeletal disorders is needed among young musicians playing the various
      instruments.

PMID- 24925173
TI  - Knee injury patterns in young irish dancers.
AB  - OBJECTIVE: To characterize knee injury patterns in Irish dancers. METHODS: A
      retrospective chart review was performed for Irish dancers under age 19 who
      presented with knee injuries to the sports medicine or orthopedic clinic from
      January 1, 2000 to December 31, 2010. Data were collected on all knee injuries
      partially or directly related to Irish dance. Injury was defined as dance-related
      pain or damage to the structures in the knee that resulted in evaluation in the
      clinic. Survey data were collected to determine the number of different
      schools/studios represented by the dancers in the study. RESULTS: Sixty-seven
      Irish dancers with 86 knee injuries were evaluated. Half (50.7%) of these
      patients received more than one diagnosis during these visits. Overuse injuries
      accounted for 90.7% of knee injuries. Time to presentation ranged from less than
      1 week to over 1 year. There was a significant difference in time to
      presentation, with traumatic injuries being evaluated sooner than overuse
      injuries. The most common diagnoses, accounting for 53.5% of injuries, were
      patellar tracking disorders, including patellofemoral syndrome, hypermobile
      patella, and patellar subluxation. CONCLUSION: In Irish dance overuse injuries
      represent the great majority of knee injuries, and patellofemoral tracking
      disorders are the most common diagnosis. For many dancers, there is often a delay
      of weeks to months between the onset of symptoms and evaluation in clinic.
      Prevention programs could potentially eliminate a large portion of knee pain
      experienced by young Irish dancers.

PMID- 24925174
TI  - Playing-related musculoskeletal disorders among icelandic music students:
      differences between students playing classical vs rhythmic music.
AB  - Most research studies investigating the prevalence of musculoskeletal disorders
      affecting musicians and music students have focused on classical music, while
      less is known about their prevalence in other music genres. The purpose of this
      study was to document cumulative and point prevalence of playing-related
      musculoskeletal disorders (PRMD) among music students in Iceland and,
      specifically, to identify differences between those studying classical vs
      rhythmic music. We hypothesized that students of classical music would report
      more frequent and more severe musculoskeletal disorders than students involved in
      rhythmic music, as classical instruments and composition typically require more
      demanding, sustained postures during practice and performance. A total of 74
      students from two classical music schools (schools A and B) and 1 rhythmic school
      (school C) participated in the study by answering a questionnaire assessing
      PRMDs. The results showed that 62% of participants had, at some point in their
      musical career, suffered a PRMD. The cumulative prevalence was highest in music
      school A (71.4%) and lowest in music school C (38.9%). A statistically
      significant difference was identified between the cumulative prevalence of PRMD
      from schools A and B combined compared to music school C (p=0.019). Over 40% of
      participants reported a "current PRMD," and a significant difference was
      identified between the three schools (p=0.011), with the highest point prevalence
      being registered in music school A (66.6%) and the lowest in music school C
      (22.2%). The prevalence of PRMDs among Icelandic music students was high. The
      difference found between students who play classical vs rhythmic music may be
      explained by different demands of the instruments and composition on playing
      posture.

PMID- 24925175
TI  - Playing-Related Problems among Musicians of the Orquesta Buena Vista Social
      Club(r) and Supporting Bands.
AB  - BACKGROUND: The Orquesta Buena Vista Social Club(r) is a world-renowned group of
      Cuban musicians accomplished in a variety of musical styles. The musicians of the
      Orquesta Buena Vista Social Club and supporting musicians of their orchestras
      represent a cohort of musicians throughout Cuba who continue to play traditional
      genres and perform into their older ages. PURPOSE: The purpose of the study was
      to (1) identify musculoskeletal conditions that occurred over the previous 12
      months among the members of the Orquesta and supporting musicians and (2) to
      discover if these conditions, in part, were caused by or in some way affected
      musical performance. METHODS: The study was a convenience sample of musicians
      within the Orquesta Buena Vista Social Club and supporting musical groups. Thirty
      six musicians completed a self-administered survey. RESULTS: Sixty-seven percent
      (24/36) of the total sample of musicians and 89% (16/18) of those over age 60
      years had at least one musculoskeletal condition over the previous 12 months.
      Forty-four percent (16/36) of the total sample of musicians and 61% (11/18) of
      those older than 60 years of age reported that a musculoskeletal complaint was
      either, in part, caused by or affected their performance. CONCLUSION:
      Musculoskeletal conditions were prevalent among the Cuban musicians, especially
      in those over 60 years of age. Collaboration of medical professionals, managers,
      and musicians may help to generate ideas on how to prevent injuries as well as to
      evaluate what treatments for playing-related conditions, including both
      conventional and complementary and alternative therapies, are most effective.

PMID- 24925176
TI  - Comparing violinists' body movements while standing, sitting, and in sitting
      orientations to the right or left of a music stand.
AB  - OBJECTIVES: For violinists, it is common practice to play while standing or
      sitting. When playing in an orchestra, generally two persons share one music
      stand, with one sitting to the right and the other to the left of the stand. The
      present study investigated specific movement patterns while playing in these
      different positions. METHODS: Using a posturographic device and 3D motion
      capture, the body weight distributions and specific body movements of 19
      violinists were analyzed. RESULTS: Results showed unbalanced weight distributions
      while sitting in front of or oriented to the right of the music stand compared to
      the almost even distributions while standing or oriented to the left of the
      stand. Analyses of movement patterns showed significant differences between
      standing and sitting, mainly in the upper body parts with less movability while
      sitting. While sitting in front of or oriented to the right of the music stand,
      the right bowing arm showed more restricted movements compared to other
      positions. CONCLUSION: The playing positions are discussed with regard to
      possible physiological stress and health risks. The study emphasizes the
      importance of different playing positions and offers starting points for
      discussion of postural influences and sensible handling of the instrument in
      performance and practice for violinists.

PMID- 24925177
TI  - Injury and the orchestral environment: part II. Organisational culture,
      behavioural norms, and attitudes to injury.
AB  - The organisational culture, behavioural norms, and attitudes of a workplace have
      a profound influence on levels of injury and illness amongst its workers. While
      this is well established in Work Health and Safety literature, very little
      research has attempted to understand the influence of organisational culture on
      injury risk in the orchestral profession. To address this, the current study
      aimed to investigate the influence of organisational culture on injury outcomes
      for orchestral musicians. Using a qualitative case study methodology, in-depth
      semi-structured interviews were undertaken with 10 professional orchestral
      cellists (2 freelance and 8 fulltime members) from a single Australian orchestra.
      After initial data analysis, further interviews were undertaken with a set of 5
      orchestral management staff as a means of data triangulation. All data were
      analysed using a themes-based "analysis of narrative" approach. The findings
      indicate that an orchestral culture exists in which musicians see injury as a
      sign of weakness, failure, and poor musicianship. Such negative perceptions of
      injury influence musicians to play through considerable levels of pain and
      continue performing with injuries. Because of perceived judgment from the
      orchestral group, musicians were found to conceal injuries from colleagues and
      management staff. Freelance musicians felt that disclosing injuries may lead to
      decreased work opportunities, and both full-time and casual musicians felt that
      "opening up" about injury may subject them to group judgment about their
      technique or musicianship. The study suggests education measures which may be
      effective at influencing individual behaviours and attitudes as well as cultural
      change initiatives which could lead to long-term positive health outcomes in the
      orchestral workplace.

PMID- 24925178
TI  - Fit to dance survey: a comparison with dancesport injuries.
AB  - The Fit to Dance survey has been conducted twice previously, in 1993 and 2002,
      without dancesport participants. The purpose of this present online survey was to
      supplement a comparison of dancesport against the earlier results. The current
      study had a greater percentage of male respondents than previous studies (43% vs
      24% and 26%). The dancesport participants were older (28% at 40+ yrs vs 3% and
      1%) and more likely to have normal (69% vs 57%) to overweight BMI (18% vs 2%).
      Dancesport participants spent more time in various non-dancing conditioning
      activities than previous surveys (5.2 +/- 3.9 hrs SD vs 1.9 +/- 2.5 and 2.2 +/-
      2.7). Muscles and joints were the most common type of injury in all the surveys.
      The knee was the top injury site in this survey, with lower back in previous
      surveys. The main perceived cause of injury was repetitive movements, whereas
      fatigue and overwork were cited in the previous surveys. Physiotherapists were
      the most common type of medical professionals from whom the dancers sought
      treatment for their injuries in all surveys. The first survey included
      recommendations that the present survey results agree with, including: dancers
      should be physically fit, dancers should warm up and cool down, dancers should
      never have to work in unsuitable environments, and dancers should receive
      immediate high-quality treatment for injuries.

PMID- 24925179
TI  - Physical activity helps to control music performance anxiety.
AB  - We evaluated if regular physical activity could influence musical performance
      anxiety (MPA) in college music students. Levels of MPA, as measured with the
      Kenny MPA Inventory, and a survey about the physical activity habits were
      obtained from 87 students of music. The results showed that physically active
      musicians had lower MPA scores (p<0.05) than non-active ones, independent of
      gender. We conclude that there is an association between physical activity and
      minor MPA, and studies with a longitudinal design should be done to explore this
      important issue.

PMID- 24925180
TI  - Mental problems among first-year conservatory students compared with medical
      students.
AB  - Musical education and the musical profession can be stressful, which may make
      musicians vulnerable for stress-related disorders. To determine if music students
      are particularly at risk for mental problems, we used the Standardised Assessment
      of Personality-Abbreviated Scale (SAPAS) and the Symptom Questionnaire (SQ48S) to
      compare symptoms in first-year conservatory students (n=33) and first-year
      medical students (n=43). On the SAPAS, we found that medical students have
      significantly more difficulty making and keeping friends (p=0.015). Also, we
      observed a trend that conservatory students lose their temper more easily
      (p=0.040). Both student groups showed high scores for the personality trait
      "perfectionism." On the SQ48, we observed a trend that both conservatory and
      medical students experience more psychological problems than the general
      population, but there were no significant differences between conservatory
      students and medical students in the total scores of both questionnaires.

PMID- 24925181
TI  - "Suffering twice": the gender politics of cesarean sections in Taiwan.
AB  - Women's pursuit of medical interventions in childbirth has been a challenging
      issue in feminist and medical anthropological research on the medicalization of
      reproduction. This article addresses the gender politics surrounding maternal
      requests for cesarean sections in Taiwan. Since the 1990s, Taiwanese cesarean
      rates have been reported as among the highest in the world. That is not the case
      now, yet they are still perceived as such, and the current rate of 37% is indeed
      high by any standards. The government and public discourses attribute the high
      cesarean rate to women's demand for this intervention. However, my ethnographic
      research indicates that the Taiwanese hospital birthing system leads to the
      prevalence of cesareans, and that women's requests for them constitute strategic
      responses to the system and its existing high cesarean rates. Using women's
      attempt to avoid "suffering twice" as an example, I argue that maternal requests
      for cesareans often lie at the intersection between their restricted control over
      childbirth and their agency within the medical system. 

PMID- 24925182
TI  - Roles for root iron plaque in sequestration and uptake of heavy metals and
      metalloids in aquatic and wetland plants.
AB  - Toxic metal(loid) contamination of soil and sediment poses long term risk to soil
      and human health through plant-human or plant-animal-human food chain pathways.
      Iron plaque (IP) formation is frequent in aquatic and wetland plant species and
      is responsible for the sequestration of various metal(loids). The presence of IP
      may act as a buffer or barrier and may thus enhance or reduce the uptake of
      potentially phytotoxic metals and metalloids by plants. If IP acts as a barrier,
      then low IP producing macrophytes/aquatic plants may be better accumulators of
      toxic metals and may find use in constructed wetlands for remediation of
      pollutants, while high IP forming edible plant species could be safer for human
      consumption. Conversely, if IP acts as a buffer for mineral nutrients and toxic
      elements then those cultivars may be rich in nutrients, but may also cause
      toxicity. However, an ecotoxicological risk is also inevitable if IP rich
      macrophyte roots containing heavy metals are consumed by herbivores. In this
      review, we summarize the current understanding about the role of IP in metal and
      metalloid sequestration, uptake, and transport. Furthermore, we will address the
      role of root IP in Oryza sativa for arsenic (As) sequestration leading to lower
      grain As translocation, reducing the risk of human exposure. 

PMID- 24925184
TI  - A radiotelemetry system for analyzing heart rate responses during playback
      experiments in blackbirds (Turdus merula ).
AB  - In acoustical stimulus-response tests on European blackbirds (Turdus merula ) in
      cages and an outdoor aviary, alteration in heart rate (HR) was used to measure
      reaction strenght. HR was measured by radiotelemetry. The miniature transmitters
      newly developed for this task had to fulfill the following requirements:
      Simultaneous recordings of HR in several interacting animals; uninterrupted
      transmission of HR signals, sufficient range and battery life combined with low
      weight and easy handling properties. The miniature transmitters successfully used
      in this experiment had a quartz-stabilized oscillator. They weighed between 4.1
      and 5.2 g and had a range of 3 m and a lifetime of 72 hrs (circuit diagram,
      Fig.1). The transmitted signal corresponded to a unitary impulse representing the
      S-wave of the ECG (Fig. 4b). Implanted electrodes were used to record ECG
      potentials. The transmitter was carried by the birds like a small rucksack tied
      to their backs. Electrode implantation and transmitter installation are described
      in detail. HR signals stored on audio tape were later transformed to frequency
      curves on a chart recorder (Fig. 3, 4a). Typical HR response curves are shown
      (Fig. 5). Statistical analysis of the data was performed on a DEC-PDP-11 computer
      using a special set of programs. The system has been successfully used to provide
      answers to experimental questions not previously obtainable with classical
      methods. 

PMID- 24925183
TI  - Institutional volume of heart transplantation with left ventricular assist device
      explantation influences graft survival.
AB  - BACKGROUND: There are increasing numbers of patients undergoing orthotopic heart
      transplantation (OHT) with left ventricular assist device (LVAD) explantation
      (LVAD explant-OHT). We hypothesized that LVAD explant-OHT is a more challenging
      surgical procedure compared to OHT without LVAD explantation and that
      institutional LVAD explant-OHT procedural volume would be associated with post
      transplant graft survival. We sought to assess the impact of institutional volume
      of LVAD explant-OHT on post-transplant graft survival. METHODS: This is a
      retrospective analysis of the Scientific Registry of Transplant Recipients for
      adult OHTs with long-term LVAD explantation. LVAD explant-OHT volume was
      characterized on the basis of the center's year-specific total OHT volume
      (OHTvol) and year-specific LVAD explant-OHT volume quartile (LVADvolQ). The
      effect of LVADvolQ on graft survival (death or re-transplantation) was analyzed.
      RESULTS: From 2004 to 2011, 2,681 patients underwent OHT with LVAD explantation
      (740 with HeartMate XVE, 1,877 with HeartMate II and 64 with HeartWare devices).
      LVAD explant-OHT at centers falling in the lowest LVADvolQ was associated with
      reduced post-transplant graft survival (p = 0.022). After adjusting for
      annualized OHTvol (HR = 0.998, 95% CI 0.993 to 1.003, p = 0.515 and pulsatile XVE
      (HR = 0.842, 95% CI 0.688 to 1.032, p = 0.098), multivariate analysis confirmed a
      significantly (approximately 37%) increased risk of post-transplant graft failure
      among explant-OHT procedures occurring at centers in the lowest volume quartile
      (HR = 1.371, 95% CI 1.030 to 1.825, p = 0.030). CONCLUSION: Graft survival is
      decreased when performed at centers falling in the lowest quartile of LVAD
      explant-OHT for a given year. This volume-survival relationship should be
      considered in the context of limited donor organ availability and the rapidly
      growing number of LVAD centers.

PMID- 24925185
TI  - Delaying reinforcement in an autoshaping task generates adjunctive and
      superstitious behaviors.
AB  - Rats were autoshaped to touch a lever upon its insertion into an operant chamber
      on a 45 s random time schedule. Occurrence of a reinforced touch on each of 12
      lever insertions per session and nose-pokes at the retracted lever were
      monitored, as was exploratory rearing activity. Delays of 2, 4 or 8 s interposed
      between the retraction of the lever, which occurred either after 15 s or after a
      touch response, and delivery of the food pellet reward, resulted in progressively
      slower acquisition of the extended lever touch response. However, if rats had
      already acquired the response under immediate reinforcement conditions, the
      delays subsequently introduced did not cause a decline in autoshaped touch
      responding. Nose-pokes at the retracted lever occurred during both intertrial and
      reinforcement delay intervals over the course of autoshaping. The appearance and
      frequency of these (adjunctive or superstitious) behaviors depended upon the
      reinforcement delay and behavioral history. These interval behaviors offer
      measurements of learning not based on arbitrary criteria; they thus provide
      information about effects on endpoints, or a more global approach to learning. 

PMID- 24925186
TI  - Temporal responses to environmental scale in the lizard Anolis carolinensis
      (reptila, lacertilia, iguanidae).
AB  - An influence of spatial scale on temporal processing has been described in humans
      (De Long, 1981). The hypothesis that a similar relationship exists in reptiles
      was tested by placing twelve lizards in volumetrically constant but large-scale
      or small-scale "home" environments and alternately exposing them to large and
      small scale novel environments in a counterbalanced design. Behavioral measures
      included latencies and frequencies for four types of behavior associated with
      behavioral arousal and exploration and for duration of behavioral states. Results
      indicate (1) behavioral latencies are significantly reduced in small-scale novel
      environments and (2) as predicted, the ratio of latencies in large-scale divided
      by small-scale novel environments is essentially identical to the ratio of the
      scales of the environments themselves. Linear regression analyses relating
      latencies to the ratio yield results remarkably similar to those previously
      reported for temporal experience and spatial scale in human subjects. This
      research suggests that an experiential temporal-spatial relativity may be
      phylogenetically primitive. 

PMID- 24925187
TI  - The aggressive behaviour between territorial Pseudocrenilabrus multicolor
      (pisces, cichlidae) with unlimited or only visual contact.
AB  - The development of aggression between territorial fish has mainly been studied in
      laboratory experiments using only visual contact. In this study, comparisons of
      the aggressive behaviour were made between conditions of unlimited and only
      visual contact. Fighting between two territorial cichlids in direct contact
      decreased over time in a way similar to the aggressive activity between subjects
      permitted only visual contact. However, there were also important differences
      between the two conditions of contact. Low-intensity aggression with a distance
      between the subjects occurred frequently in free interaction but was generally
      not observed under conditions of visual contact. The presence of non-territorial
      fish increased the aggression between subjects with visual contact but conversely
      had no influence on fighting and decreased low-intensity aggression between
      freely interacting subjects. In addition, the low level of aggression after some
      time of unlimited contact was not transferred to a subsequent period of visual
      contact. The results indicate that the decrease of aggression under conditions of
      visual contact is caused by habituation, whereas in a free interaction a balance
      is also developed between attack and escape tendencies. 

PMID- 24925188
TI  - The aggressive behaviour between territorial Astatotilapia burtoni (pisces,
      cichlidae) with unlimited or only visual contact emphasizing low-intensity
      aggression during free interaction.
AB  - The relationship between territorial Astatotilapia burtoni was studied under
      conditions of both unlimited and only visual contact. The aggressive activity
      between territorial fish coming into visual contact remained at a high level
      during the seven days of observation. Territorial fish permitted unlimited
      contact showed, on the other hand, a marked decreased intensity of aggression
      during the first day of contact. Results from experiments using visual contact
      are therefore not necessarily relevant for a free contact situation. A detailed
      examination of low-intensity aggression indicated that a dynamic equilibrium
      between attack and escape tendencies, as regulated by distance to the territorial
      border, controlled aggression between freely interacting fish. Low-intensity
      aggression seldom occurred between fish separated by a glass partition and a
      similar equilibrium did not seem to develop in this situation. The difference
      between the findings on A. burtoni and results from similar experiments on
      another cichlid fish Pseudocrenilabrus multicolor could be explained by
      differences in the relative importance of two factors in the regulation of
      aggression; (1) a balance between attack and escape tendencies and (2) a decrease
      of the attack tendency (habituation) below a critical threshold value. 

PMID- 24925189
TI  - Time budgets and behavioural synchronization in aggregated and isolated male and
      female mice.
AB  - Albino mice (Mus musculus ), initially housed in single sex groups and,
      subsequently, in social isolation, were used in this study to analyze the
      influence of social companions on the amount and on the distribution throughout
      the day of several behaviours. An observational recording technique was employed
      to record behaviour during the dark phase of the day. Behavioural sex differences
      in grouped mice were observed in four out of six behavioural categories. Females
      generally proved to be more active than males. Furthermore, prolonged social
      housing conditions resulted in an increase in male social interactions, in
      concomitance with changes in their time budgets. Conversely, females showed a
      decrease over time in social interactions with only slight effects on their time
      budget. Isolation seemed to increase slightly both male and female activity
      levels. Subjects housed together generally showed significantly similar Rest,
      Feed and General Activity patterns throughout the dark phase of the day. By
      contrast, the averaged patterns of different groups generally proved to be
      dissimilar in grouped females, but not in grouped males. When isolated, mice
      showed a distribution of their activities throughout the day different from what
      they had displayed under social conditions. These data indicate that social
      environment has an effect on the individual activity profiles which results in a
      definite synchronization within female groups and in a tendency towards
      desynchronization within male groups. 

PMID- 24925190
TI  - Distribution and timing of distant metastasis after local therapy in a large
      cohort of patients with esophageal and esophagogastric junction cancer.
AB  - BACKGROUND: Patients with localized esophageal and esophagogastric junction
      cancer (EAC) receive chemoradiation and then surgery (trimodality, TMT) or
      definitive chemoradiation (bimodality, BMT). Distant metastases (DMs) are common
      but the details of their distribution and timing in a large cohort have not been
      described. METHODS: 629 patients with localized EAC who had TMT or BMT were
      analyzed. Standard statistical methods were used to define the end points.
      RESULTS: The median follow-up time was 37.2 months (interquartile range 17.8
      65.0). Of 356 TMT patients, 33% (119) developed DM as their first relapse and of
      273 BMT patients, 40% (109) developed DM; 91% (TMT) and 96% (BMT) of the DMs were
      diagnosed within 2 years of local therapy. The most common sites of DM were:
      lung, distant nodes, liver, peritoneal cavity, bone, brain and pleura in order of
      frequency. The median overall survival of TMT patients with DM was 10.2 months
      (95% CI 7.8-12.7) and that for BMT patients with DM was 7.8 months (95% CI 5.7
      9.9). CONCLUSIONS: Following TMT or BMT, >=33% of patients developed DMs and most
      of these occurred within 2 years (>90%) of local therapy. A clinical model is
      desirable that associates clinical parameters with a high risk for DM in TMT
      eligible patients prior to surgery.

PMID- 24925191
TI  - Developing a short version of the test anxiety scale for baccalaureate nursing
      skills test--a preliminary study.
AB  - AIM: In this study, a brief and rapid skills test anxiety scale was developed to
      measure nursing students' anxiety before their first skills assessment test, and
      the measurement results were assessed using factor analysis. METHODS: A survey
      questionnaire design was used to gather cross-sectional data for the scale. The
      study subjects comprised 250 first-year bachelors of nursing students who
      completed a test anxiety survey before taking their first nursing skills test.
      This questionnaire evaluated first-year baccalaureate students' anxiety
      associated with applying nursing skills. RESULTS: The results indicated that
      students were most anxious about the attitudes of the teachers proctoring the
      tests (94.6%), followed by the test atmosphere (92.2%). These 2 items were
      determined to be conducive to high anxiety and were statistically correlated.
      Exploratory analysis was used to extract 2 common factors, nonspecific
      information and test atmosphere. Meanwhile, factor loadings were 19.45% and
      50.41%, respectively. CONCLUSION: This study evaluated the validity and
      reliability of the proposed scale. The evidence-based results presented in this
      investigation provide teachers with a crucial reference for helping students
      reduce their anxiety before their first skills assessment test.

PMID- 24925193
TI  - Doubt in the psychoanalysis of a paedophile.
AB  - In this single case study, I will address the question of how incestuous sexual
      abuse causes doubt of three distinct types: (1) honest doubt that is essential to
      the pursuit of knowledge; (2) inherent doubt that can result from a trauma that
      leaves the victim's mind fragmented and confused; and (3) the sadistic imposition
      of doubt intended to deceive, disorient and attack unbearable knowledge in the
      victim or another person familiar with the abuse (in this case, the analyst and
      the victim's later victims). During the course of my psychoanalysis of a
      paedophile, it became clear that this third form of doubt played an integral role
      in the patient's sexual abuse of children, a role I will link to the nature and
      function of paedophilia and to the experience of working psychoanalytically with
      a paedophile. 

PMID- 24925192
TI  - Elevated gene expression of glutamate receptors in noradrenergic neurons from the
      locus coeruleus in major depression.
AB  - Glutamate receptors are promising drug targets for the treatment of urgent
      suicide ideation and chronic major depressive disorder (MDD) that may lead to
      suicide completion. Antagonists of glutamatergic NMDA receptors reduce depressive
      symptoms faster than traditional antidepressants, with beneficial effects
      occurring within hours. Glutamate is the prominent excitatory input to the
      noradrenergic locus coeruleus (LC). The LC is activated by stress in part through
      this glutamatergic input. Evidence has accrued demonstrating that the LC may be
      overactive in MDD, while treatment with traditional antidepressants reduces LC
      activity. Pathological alterations of both glutamatergic and noradrenergic
      systems have been observed in depressive disorders, raising the prospect that
      disrupted glutamate-norepinephrine interactions may be a central component to
      depression and suicide pathobiology. This study examined the gene expression
      levels of glutamate receptors in post-mortem noradrenergic LC neurons from
      subjects with MDD (most died by suicide) and matched psychiatrically normal
      controls. Gene expression levels of glutamate receptors or receptor subunits were
      measured in LC neurons collected by laser capture microdissection. MDD subjects
      exhibited significantly higher expression levels of the NMDA receptor subunit
      genes, GRIN2B and GRIN2C, and the metabotropic receptor genes, GRM4 and GRM5, in
      LC neurons. Gene expression levels of these receptors in pyramidal neurons from
      prefrontal cortex (BA10) did not reveal abnormalities in MDD. These findings
      implicate disrupted glutamatergic-noradrenergic interactions at the level of the
      stress-sensitive LC in MDD and suicide, and provide a theoretical mechanism by
      which glutamate antagonists may exert rapid antidepressant effects. 

PMID- 24925194
TI  - Embracing team-based oncology care.

PMID- 24925195
TI  - Successful imatinib therapy for neuroendocrine carcinoma with activating Kit
      mutation: a case study.
AB  - Neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are
      believed to originate from the cells of Cajal that are randomly dispersed along
      the aerodigestive tract. Despite their distinct morphologic appearance, NET and
      GIST may share oncogenic mechanisms. Often presenting in the metastatic setting,
      treatment options for patients with NET are limited. This case report presents a
      patient with refractory metastatic NET that did not respond conventional
      chemotherapy. The patient was treated with a KIF11 inhibitor in a phase I
      clinical trial and experienced a prolonged and clinically meaningful partial
      response. On progression at 20 months, the patient's tumor was sequenced to
      reveal a KIT exon 11 mutation. Institution of imatinib therapy achieved a rapid
      and sustained antitumor effect with profound clinical benefit. Despite previously
      reported KIT expression in NET, this is the first documented case of an
      activating KIT mutation in NET and of successful treatment with both a KIF11
      inhibitor and imatinib, each of which was elucidated through molecular profiling
      of the patient's tumor. Imatinib may be a valuable therapy in NET harboring
      activating KIT mutations.

PMID- 24925196
TI  - Gastrointestinal stromal tumors, version 2.2014.
AB  - Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of
      the gastrointestinal tract, resulting most commonly from KIT or platelet-derived
      growth factor receptor alpha (PDGFRalpha)-activating mutations. These NCCN
      Guideline Insights highlight the important updates to the NCCN Guidelines for
      Soft Tissue Sarcoma specific to the management of patients with GIST experiencing
      disease progression while on imatinib and/or sunitinib.

PMID- 24925197
TI  - Dermatofibrosarcoma protuberans, version 1.2014.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor
      characterized by a relatively high risk of local recurrence and low risk of
      metastasis. The NCCN Guidelines for DFSP provide multidisciplinary
      recommendations on the management of patients with this rare disease. These NCCN
      Guidelines Insights highlight the addition of the Principles of Pathology
      section, which provides recommendations on the pathologic assessment of DFSP.
      Because DFSP can mimic other lesions, immunohistochemical studies are often
      required to establish diagnosis. Cytogenetic testing for the characteristic
      translocation t(17;22)(q22;q13) can also be valuable in the differential
      diagnosis of DFSP with other histologically similar tumors.

PMID- 24925199
TI  - Optimal first-line and maintenance treatments for advanced-stage nonsquamous non
      small cell lung cancer.
AB  - During the past 10 years, the treatment of advanced-stage non-small cell lung
      cancer (NSCLC) has become increasingly complex, and debate continues regarding
      the optimal chemotherapeutic agents and duration of treatment. The addition of
      bevacizumab to platinum doublet chemotherapy, the use of pemetrexed for
      nonsquamous histology, and the introduction of maintenance chemotherapy are
      strategies that have been shown to improve overall survival beyond 12 months.
      Many acceptable treatment options are recommended in the NCCN Clinical Practice
      Guidelines in Oncology for NSCLC. This article discusses the first-line treatment
      of NSCLC with no identifiable mutations with FDA-approved targeted therapies for
      patients treated outside a clinical trial, particularly focusing on difficult
      clinical decisions, such as when the use of bevacizumab is appropriate, choosing
      a platinum partner, and treatment of patients with an ECOG performance status of
      2. Data are summarized from several recent maintenance clinical trials, such as
      PARAMOUNT, AVAPERL, and PointBreak, and the implications these trials have on
      practical decisions oncologists must make when choosing an optimal treatment
      strategy for patients with advanced NSCLC are discussed.

PMID- 24925198
TI  - Survivorship: fatigue, version 1.2014.
AB  - Many cancer survivors report that fatigue is a disruptive symptom even after
      treatment ends. Persistent cancer-related fatigue affects quality of life,
      because individuals become too tired to fully participate in the roles and
      activities that make life meaningful. Identification and management of fatigue
      remains an unmet need for many cancer survivors. This section of the NCCN
      Guidelines for Survivorship provides screening, evaluation, and management
      recommendations for fatigue in survivors. Management includes education and
      counseling, physical activity, psychosocial interventions, and pharmacologic
      treatments.

PMID- 24925200
TI  - Insights into preferences for psycho-oncology services among women with
      gynecologic cancer following distress screening.
AB  - Much attention has been given to implementing routine screening programs in
      cancer care to improve the management of distress following diagnosis. Although
      patients might screen positive for distress, several studies have found that most
      then refuse additional psychosocial support. To inform the development of
      successful models of distress screening, this qualitative study explored
      preferences for psychosocial care among 18 women diagnosed with a gynecologic
      cancer who scored at least 4 on the Distress Thermometer (DT). Participants were
      recruited from a gynecologic oncology outpatient clinic in Newcastle, Australia,
      and interviewed. Unanimously, participants felt that completing the DT was an
      integral part of their cancer care. However, half then refused the referral to
      see a psychologist. These women typically reported that a referral was not
      needed, because their rating on the DT reflected transient stressors or physical
      distress. Many also spoke about their need to cope with the challenges they were
      facing on their own and the extensive social support they already had in place to
      help them overcome these challenges. In contrast, women who accepted referral to
      the psychologist often struggled to cope with several losses they felt had
      existential and long-term effects. Commonly, these women reported not having the
      social support they needed, managing several concurrent life stressors, and/or
      not having the repertoire of coping skills they required to "remain afloat."
      Findings from this study begin to bridge the gap between clinicians' and
      patients' expectations of how psychosocial services should be used in response to
      distress screening.

PMID- 24925201
TI  - False-positive elevations of carcinoembryonic antigen in patients with a history
      of resected colorectal cancer.
AB  - Routine monitoring of carcinoembryonic antigen (CEA) levels is standard in
      patients with resected colorectal cancer (CRC). The incidence of false-positives
      and the upper limits of false-positive elevations have not been previously well
      characterized. A search of medical records at Memorial Sloan-Kettering Cancer
      Center identified 728 patients who underwent an R0 resection of locoregional CRC
      between January 2003 and December 2012 and who had an increase in CEA level above
      the normal range after a normal perioperative CEA level. Of these, 358 had a
      false-positive elevation of CEA level, 335 had a true-positive elevation
      indicative of recurrent CRC, and 35 had a true-positive elevation indicative of
      the development of a new, non-CRC malignancy. Of those with false elevations, 111
      had a single isolated CEA level elevation (median highest CEA level of 5.5 ng/mL)
      with no further abnormal measurements, whereas 247 had elevations on 2 or more
      readings, with a median highest level of 6.7 ng/mL. Of these 247 patients with
      confirmed false-positive CEA level elevations, only 5 (2%) had measurements
      greater than 15 ng/mL, and no confirmed elevation greater than 35 ng/mL was a
      false-positive. False-positive CEA test results in the range of 5 to 15 ng/mL are
      common. Confirmation of CEA elevation in this range before initiating imaging
      studies may be appropriate. False-positive results greater than 15 ng/mL are
      rare, and all confirmed CEA levels greater than 35 ng/mL were associated with
      cancer recurrence.

PMID- 24925202
TI  - Non-Hodgkin's lymphomas, version 2.2014.
AB  - Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative
      disorders originating in B lymphocytes, T lymphocytes, or natural killer cells.
      Follicular lymphoma (FL) is the most common subtype of indolent NHL, accounting
      for approximately 22% of all newly diagnosed cases of NHL. The incorporation of
      rituximab to chemotherapy regimens has become a widely accepted standard of care
      for first-line therapy for patients with FL. Maintenance and consolidation
      therapy with rituximab and radioimmunotherapy have also been associated with
      improved progression-free survival in patients experiencing response to first
      line therapy. Despite therapeutic advances that have improved outcomes, FL is
      generally considered a chronic disease characterized by multiple recurrences with
      current therapies. This manuscript discusses the recommendations outlined in the
      NCCN Guidelines for the diagnosis and management of patients with FL.

PMID- 24925203
TI  - TheAlliance for Quality Psychosocial Cancer Care: an innovative model for
      disseminating and improving implementation of national quality care
      recommendations.

PMID- 24925205
TI  - Lack of association between serotonin transporter 5-HTT gene polymorphism and
      endometriosis in an Italian patient population.
AB  - BACKGROUND: The aim of this study was to determine whether the serotonin
      transporter gene (5-HTT), a key component in the control of the serotonergic
      system, is associated with endometriosis in an Italian population. FINDINGS: A
      case-control study, comprising 137 Italian patients with surgically confirmed
      endometriosis and 120 healthy controls, was carried out. 5-HTT genotypes (LL, SL
      and SS) were obtained by polymerase chain reaction and gel electrophoresis
      analysis. We found no overall difference in genotypic and allelic distributions
      of the 5-HTT gene between cases and controls. CONCLUSIONS: Our results suggest
      that the 5-HTT L/S promoter polymorphism is not associated with susceptibility to
      endometriosis in the studied Italian patients.

PMID- 24925206
TI  - Effects of vector backbone and pseudotype on lentiviral vector-mediated gene
      transfer: studies in infant ADA-deficient mice and rhesus monkeys.
AB  - Systemic delivery of a lentiviral vector carrying a therapeutic gene represents a
      new treatment for monogenic disease. Previously, we have shown that transfer of
      the adenosine deaminase (ADA) cDNA in vivo rescues the lethal phenotype and
      reconstitutes immune function in ADA-deficient mice. In order to translate this
      approach to ADA-deficient severe combined immune deficiency patients, neonatal
      ADA-deficient mice and newborn rhesus monkeys were treated with species-matched
      and mismatched vectors and pseudotypes. We compared gene delivery by the HIV-1
      based vector to murine gamma-retroviral vectors pseudotyped with vesicular
      stomatitis virus-glycoprotein or murine retroviral envelopes in ADA-deficient
      mice. The vesicular stomatitis virus-glycoprotein pseudotyped lentiviral vectors
      had the highest titer and resulted in the highest vector copy number in multiple
      tissues, particularly liver and lung. In monkeys, HIV-1 or simian
      immunodeficiency virus vectors resulted in similar biodistribution in most
      tissues including bone marrow, spleen, liver, and lung. Simian immunodeficiency
      virus pseudotyped with the gibbon ape leukemia virus envelope produced 10- to 30
      fold lower titers than the vesicular stomatitis virus-glycoprotein pseudotype,
      but had a similar tissue biodistribution and similar copy number in blood cells.
      The relative copy numbers achieved in mice and monkeys were similar when adjusted
      to the administered dose per kg. These results suggest that this approach can be
      scaled-up to clinical levels for treatment of ADA-deficient severe combined
      immune deficiency subjects with suboptimal hematopoietic stem cell
      transplantation options. 

PMID- 24925207
TI  - Gene transfer properties and structural modeling of human stem cell-derived AAV.
AB  - Adeno-associated virus (AAV) vectors are proving to be remarkably successful for
      in vivo gene delivery. Based upon reports of abundant AAV in the human marrow, we
      tested CD34(+) hematopoietic stem cells for the presence of natural AAV. Here, we
      report for the first time, the presence of novel AAV variants in healthy CD34(+)
      human peripheral blood stem cells. The majority of healthy peripheral blood stem
      cell donors were found to harbor AAV in their CD34(+) cells. Every AAV isolated
      from CD34(+) cells mapped to AAV Clade F. Gene transfer vectors derived from
      these novel AAVs efficiently underwent entry and postentry processing in human
      cord blood stem cells and supported stable gene transfer into long-term, in vivo
      engrafting human HSCs significantly better than other serotypes. AAVHSC
      transduced human CD34(+) cells engrafted in vivo and gave rise to differentiated
      transgene-expressing progeny. Importantly, gene-marked CD34(+) stem cells
      persisted long term in xenograft recipients, indicating transduction of primitive
      progenitors. Notably, correlation of structure with function permitted
      identification of potential capsid components important for HSC transduction.
      Thus, AAVHSCs represent a new class of genetic vectors for the manipulation of
      HSC genomes. 

PMID- 24925208
TI  - Validity and reliability of a novel immunosuppressive adverse effects scoring
      system in renal transplant recipients.
AB  - BACKGROUND: After renal transplantation, many patients experience adverse effects
      from maintenance immunosuppressive drugs. When these adverse effects occur,
      patient adherence with immunosuppression may be reduced and impact allograft
      survival. If these adverse effects could be prospectively monitored in an
      objective manner and possibly prevented, adherence to immunosuppressive regimens
      could be optimized and allograft survival improved. Prospective, standardized
      clinical approaches to assess immunosuppressive adverse effects by health care
      providers are limited. Therefore, we developed and evaluated the application,
      reliability and validity of a novel adverse effects scoring system in renal
      transplant recipients receiving calcineurin inhibitor (cyclosporine or
      tacrolimus) and mycophenolic acid based immunosuppressive therapy. METHODS: The
      scoring system included 18 non-renal adverse effects organized into
      gastrointestinal, central nervous system and aesthetic domains developed by a
      multidisciplinary physician group. Nephrologists employed this standardized
      adverse effect evaluation in stable renal transplant patients using physical
      exam, review of systems, recent laboratory results, and medication adherence
      assessment during a clinic visit. Stable renal transplant recipients in two
      clinical studies were evaluated and received immunosuppressive regimens comprised
      of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and
      construct validity were assessed to document these adverse effect evaluations.
      Inter-rater reliability was determined using the Kappa statistic and intra-class
      correlation. RESULTS: A total of 58 renal transplant recipients were assessed
      using the adverse effects scoring system confirming face validity. Nephrologists
      (subject matter experts) rated the 18 adverse effects as: 3.1 +/- 0.75 out of 4
      (maximum) regarding clinical importance to verify content validity. The adverse
      effects scoring system distinguished 1.75-fold increased gastrointestinal adverse
      effects (p=0.008) in renal transplant recipients receiving tacrolimus and
      mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated
      construct validity. Intra-class correlation was 0.81 (95% confidence interval:
      0.65-0.90) and Kappa statistic of 0.68 +/- 0.25 for all 18 adverse effects and
      verified substantial inter-rater reliability. CONCLUSIONS: This immunosuppressive
      adverse effects scoring system in stable renal transplant recipients was
      evaluated and substantiated face, content and construct validity with inter-rater
      reliability. The scoring system may facilitate prospective, standardized clinical
      monitoring of immunosuppressive adverse drug effects in stable renal transplant
      recipients and improve medication adherence.

PMID- 24925209
TI  - Functional p53 can modulate the relationship between E2F-1 expression and tumor
      kinetics in Hodgkin lymphoma.
AB  - E2F-1 is the best-described member of the E2F family of transcriptional factors
      and is particularly interesting in view of its often opposing roles. Our purpose
      was to examine the immunohistochemical expression of E2F-1 in Hodgkin lymphoma
      (HL) and to correlate it with proliferation and apoptosis of the tumor,
      clinicopathological parameters and patient outcome, as well as with expression of
      the downstream molecules p53 and p21. The median percentage of E2F-1-expressing
      Hodgkin Reed-Sternberg (HRS) cells was 80.2%. A significant positive correlation
      was found between expression of E2F-1 and p53 (p = 0.034). Following
      stratification of our cases, within the group harboring functional p53, a
      statistically significant inverse correlation was identified between E2F-1 and
      Topo IIa (p = 0.019). E2F-1 is up-regulated in the context of HL and its
      expression is inversely associated with proliferation. It seems that functional
      p53 can modulate the relationship between E2F-1 expression and tumor kinetics in
      HL. 

PMID- 24925210
TI  - Cereblon expression predicts clinical response in chronic lymphocytic leukemia
      treated with a thalidomide/fludarabine regimen.

PMID- 24925212
TI  - A "PET" topic in primary mediastinal large B-cell lymphoma: positive or negative,
      and how to handle it in the end.

PMID- 24925211
TI  - Ofatumumab and bendamustine in previously treated chronic lymphocytic leukemia
      and small lymphocytic lymphoma.
AB  - Despite initial responses > 90% with fludarabine and rituximab-based regimens,
      patients with chronic lymphocytic leukemia (CLL) invariably relapse and require
      further treatment. Ofatumumab and bendamustine have each shown efficacy in
      relapsed/refractory CLL with overall response rates (ORRs) of 58% and 76%,
      respectively. Given excellent data with bendamustine and rituximab in
      relapsed/refractory CLL/small lymphocytic lymphoma (SLL), this phase II study
      evaluated the combination of ofatumumab and bendamustine in previously treated
      patients. Patients received ofatumumab 300 mg intravenously (IV) day - 7,
      followed by ofatumumab 1000 mg IV day 1 and bendamustine 70 mg/m(2) days 1 and 2
      of each 28-day cycle. Patients received 4-6 cycles depending on number of prior
      therapies, as long as well-tolerated or until progression. Of 10 patients
      enrolled, the ORR was 40% and complete response rate was 20%. The median
      progression-free and overall survivals were 8.1 months and 16.2 months. Three
      patients developed Richter transformation. The study was closed early due to
      unexpected adverse events including infusion-related reactions, infection and
      neurotoxicity. 

PMID- 24925213
TI  - Direct alignment and patterning of silver nanowires by electrohydrodynamic jet
      printing.
AB  - Highly aligned and patterned silver nanowires (Ag NWs) are investigated by using
      electrohydrodynamic (EHD) jet printing. Interaction between the flow field and
      the electric field as well as the mechanical stretching of the fiber jet can
      successfully align the Ag NWs inside the jet fiber. This technique can be applied
      in fabricating 1D nanostructures-based printed micro/nanoscale devices. 

PMID- 24925215
TI  - Enhancement of mitochondrial ATP production by the Escherichia coli cytotoxic
      necrotizing factor 1.
AB  - Mitochondria are dynamic organelles that constantly change shape and structure in
      response to different stimuli and metabolic demands of the cell. The Escherichia
      coli protein toxin cytotoxic necrotizing factor 1 (CNF1) has recently been
      reported to influence mitochondrial activity in a mouse model of Rett syndrome
      and to increase ATP content in the brain tissue of an Alzheimer's disease mouse
      model. In the present work, the ability of CNF1 to influence mitochondrial
      activity was investigated in IEC-6 normal intestinal crypt cells. In these cells,
      the toxin was able to induce an increase in cellular ATP content, probably due to
      an increment of the mitochondrial electron transport chain. In addition, the CNF1
      induced Rho GTPase activity also caused changes in the mitochondrial architecture
      that mainly consisted in the formation of a complex network of elongated
      mitochondria. The involvement of the cAMP-dependent protein kinase A signaling
      pathway was postulated. Our results demonstrate that CNF1 positively affects
      mitochondria by bursting their energetic function and modifying their morphology.

PMID- 24925217
TI  - Differentiating intraparenchymal hemorrhage from contrast extravasation on post
      procedural noncontrast CT scan in acute ischemic stroke patients undergoing
      endovascular treatment.
AB  - INTRODUCTION: This study aimed to identify the imaging characteristics that can
      help differentiate intraparenchymal hemorrhage from benign contrast extravasation
      on post-procedural noncontrast CT scan in acute ischemic stroke patients after
      endovascular treatment. METHODS: We reviewed the clinical and imaging records of
      all acute ischemic stroke patients who underwent endovascular treatment in two
      hospitals over a 3.5-year period. The immediate post-procedural CT scan was
      evaluated for the presence of hyperdense lesion(s). The average attenuation of
      the lesion(s) was measured. Intraparenchymal hemorrhage was defined as a
      persistent hyperdensity visualized on follow-up CT scan, 24 h or greater after
      the procedure. RESULTS: Of the 135 patients studied, 74 (55%) patients had
      hyperdense lesion(s) on immediate post-procedural CT scan. Follow-up scans
      confirmed the diagnosis of intraparenchymal hemorrhage in 20 of these 74
      patients. A receiver operating characteristic analysis showed that the average
      attenuation of the most hyperdense lesion can differentiate intraparenchymal
      hemorrhage from contrast extravasation with an area under the curve of 0.78 (p =
      0.001). An average attenuation of <50 Hounsfield units (HU) in the most visually
      hyperattenuating hyperdense lesion had 100 % specificity and 56% sensitivity for
      identification of contrast extravasations. Petechial hyperdensity was seen in
      46/54 (85%) patients with contrast extravasation versus 9/20 (45%) patients with
      intraparenchymal hemorrhage on the immediate post-procedural CT scan (p < 0.001).
      CONCLUSION: An average attenuation <50 HU of the most hyperattenuating hyperdense
      parenchymal lesion on immediate post-procedural CT scan was very specific for
      differentiating contrast extravasation from intraparenchymal hemorrhage in acute
      ischemic stroke patients after endovascular treatment.

PMID- 24925216
TI  - Burden of nonnucleoside reverse transcriptase inhibitor resistance in HIV-1
      infected patients: a systematic review and meta-analysis.
AB  - The prevalence of HIV drug resistance varies with geographic location, year, and
      treatment exposure. This study generated yearly estimates of nonnucleoside
      reverse transcriptase inhibitor (NNRTI) resistance in treatment-naive (TN) and
      treatment-experienced (TE) patients in the United States (US), Europe (EU), and
      Canada. Studies reporting NNRTI resistance identified in electronic databases and
      11 conferences were analyzed in three groups: (1) TN patients in one of four
      geographic regions [US, Canada, EU countries with larger surveillance networks
      ("EU1"), and EU countries with fewer data ("EU2")]; (2) TE patients from any
      region; and (3) TN patients failing NNRTI-based treatments in clinical trials.
      Analysis data included 158 unique studies from 22 countries representing 84
      cohorts of TN patients, 21 cohorts of TE patients, and 8 trials reporting
      resistance at failure. From 1995 to 2000, resistance prevalence in TN patients
      increased in US and EU1 from 3.1% to 7.5% and 0.8% to 3.6%, respectively.
      Resistance in both regions stabilized in 2006 onward. Little resistance was
      identified in EU2 before 2000, and increased from 2006 (5.0%) to 2010 (13.7%).
      One TN Canadian study was identified and reported resistance of 8.1% in 2006.
      Half of TN clinical trial patients had resistance after treatment failure at
      weeks 48-144. Resistance in TE patients increased from 1998 (10.1%) to 2001
      (44.0%), then decreased after 2004. Trends in NNRTI resistance among TN patients
      show an increased burden in the US and some EU countries compared to others.
      These findings signify a need for alternate first-line treatments in some
      regions.

PMID- 24925218
TI  - Human papilloma virus early proteins E6 (HPV16/18-E6) and the cell cycle marker
      P16 (INK4a) are useful prognostic markers in uterine cervical carcinomas in
      Qassim Region--Saudi Arabia.
AB  - Cervical cancer is a common and an important public health problem for adult
      women in developing countries. In contrast, cervical cancer incidence is low in
      Saudi Arabia. High-risk types of human papilloma viruses (HPV16 and HPV18) are
      the most significant risk factors for cervical cancer. HPV16/18-E6 oncoprotein is
      associated with HPV etiology, viral persistence and epithelial transformation.
      Cell cycle protein p16 INK4a (p16) plays an important role in the pathophysiology
      of cervical carcinomas. The aims of this study were to investigate the expression
      of HPV16/18-E6 and p16 in uterine cervical carcinomas in Qassim Region--Saudi
      Arabia, and to relate the results to the established clinicopathological
      prognostic parameters (age of the patient, educational level, birth control
      methods, number of pregnancy, smoking status, degree of histological
      differentiation, clinical stage, and lymph node metastasis) The study included 40
      specimens of uterine cervical squamous cell carcinomas diagnosed and confirmed by
      biopsy. Histopathological classification of cervical tumors cases was performed
      according to the International Federation of Gynecology and Obstetrics (FIGO).
      Immunohistochemical analysis for HPV16/18-E6 and p16 were carried out on formalin
      fixed paraffin-embedded sections of cervical tissues using avidin-biotin
      peroxidase method. There was a significant statistical correlation between
      HPV16/18-E6 expression in cervical carcinoma and nationality, smoking status and
      size of the tumor. HPV16/18-E6 oncoprotein expression in normal lymphocytes and
      endothelial cells in the tumor tissues and the adjacent normal cervical tissues
      suggest the possibility that HPV infection might spread to other organs through
      blood circulation. P16 expression has been correlated with high grade, stage of
      cervical SCC and HPV16/18-E6 expression. The current study supports the critical
      function of p16 and HPV16/18-E6 as specific markers for cervical carcinoma.
      However the potential for usage of p16 and HPV16/18-E6 as prognostic markers will
      require detailed follow data for a larger group of patients.

PMID- 24925220
TI  - Frameshift mutation of a histone methylation-related gene SETD1B and its regional
      heterogeneity in gastric and colorectal cancers with high microsatellite
      instability.
AB  - Histone methyltransferase (HMT), which catalyzes a histone methylation, is
      frequently altered in cancers at mutation and expression levels. The aims of this
      study were to explore whether SETD1B, SETDB2, and SETD2, SET domain-containing
      HMT genes, are mutated and expressionally altered in gastric (GC) and colorectal
      cancers (CRC). In a public database, we found that SETD1B, SETDB2, and SETD2 had
      mononucleotide repeats in coding sequences that might be mutation targets in
      cancers with microsatellite instability (MSI). We analyzed the mutations in 76
      GCs and 93 CRCs and found SETD1B (38.7% of GC and 35.6% of CRC with high MSI [MSI
      H]), SETDB2 (11.1% of CRC with MSI-H), and SETD2 frameshift mutations (6.7% of
      CRC with MSI-H). These mutations were not found in stable MSI/low MSI. In
      addition, we analyzed intratumoral heterogeneity (ITH) of SETD1B mutation in 6
      CRCs and found that 2 CRCs harbored regional ITH of SETD1B. We also analyzed
      SETD1B expression in GC and CRC by immunohistochemistry. Loss of SETD1B
      expression was identified in 15% to 55% of the GC and CRC with respect to the MSI
      status. Of note, the loss of expression was more common in those with SETD1B
      mutations than those with wild-type SETD1B. We identified alterations of SET
      domain-containing HMT at various levels (frameshift mutations, genetic ITH, and
      expression loss), which together might play a role in tumorigenesis of GC and CRC
      with MSI-H. Our data suggest that mutation analysis in multiple regions is needed
      for a better evaluation of mutation status in CRC with MSI-H.

PMID- 24925219
TI  - Sialidase NEU3 dynamically associates to different membrane domains specifically
      modifying their ganglioside pattern and triggering Akt phosphorylation.
AB  - Lipid rafts are known to regulate several membrane functions such as signaling,
      trafficking and cellular adhesion. The local enrichment in sphingolipids and
      cholesterol together with the low protein content allows their separation by
      density gradient flotation after extraction with non-ionic detergent at low
      temperature. These structures are also referred to as detergent resistant
      membranes (DRM). Among sphingolipids, gangliosides play important roles in
      different biological events, including signal transduction and tumorigenesis.
      Sialidase NEU3 shows high enzymatic specificity toward gangliosides. Moreover,
      the enzyme is present both at the cell surface and in endosomal structures and
      cofractionates with caveolin. Although changes in the expression level of NEU3
      have been correlated to different tumors, little is known about the precise
      distribution of the protein and its ability in modifying the ganglioside
      composition of DRM and non-DRM, thus regulating intracellular events. By means of
      inducible expression cell system we found that i) newly synthesized NEU3 is
      initially associated to non-DRM; ii) at steady state the protein is equally
      distributed between the two membrane subcompartments, i.e., DRM and non-DRM; iii)
      NEU3 is degraded via the proteasomal pathway; iv) the enzyme specifically
      modifies the ganglioside composition of the membrane areas where it resides; and
      v) NEU3 triggers phosphorylation of Akt, even in absence of exogenously
      administered EGF. Taken together our data demonstrate that NEU3 regulates the DRM
      ganglioside content and it can be considered as a modulator of Akt
      phosphorylation, further supporting the role of this enzyme in cancer and
      tumorigenesis. 

PMID- 24925221
TI  - GATA3 expression in small cell carcinoma of bladder and prostate and its
      potential role in determining primary tumor origin.
AB  - GATA3 is a sensitive marker for urothelial carcinoma. We here evaluate, for the
      first time, GATA3 expression in small cell carcinoma of bladder and prostate and
      assess its utility in the differential diagnosis with small cell carcinoma of
      lung primary. Archival tissues from 60 small cell carcinomas (12 bladder, 15
      lung, and 33 prostate primary cases) were used to build 2 tissue microarrays. We
      also assessed whole slide sections from 10 additional primary small cell
      carcinomas of bladder. GATA3 nuclear expression was evaluated using standard
      immunohistochemistry. Intensity (weak, moderate, and strong) and extent of
      expression were assessed in each tissue microarray spot. Extent positivity was
      categorized as focal (1%-25%), multifocal (>25%), and diffuse (>75%). Nuclear
      GATA3 expression was encountered in 7 bladder (7/22, 32%) and 2 lung (2/15, 13%)
      small cell carcinomas. All 33 primary prostate small cell carcinomas were
      negative. Among bladder tumors, strong and diffuse (>75%) GATA3 labeling was seen
      in 3 cases (3/22, 14%); focal positivity was observed in the 4 remaining cases
      (4/22, 18%). Both positive lung cases had only focal positivity. Our study is the
      first to reveal GATA3 expression in the small subset of lung small cell carcinoma
      that should be taken into consideration in assigning site of origin in advanced
      small cell carcinoma cases. Our novel finding of GATA3 positivity in one-third of
      bladder small cell carcinoma is of potential value in differentiating small cell
      carcinomas of prostate origin from those of bladder origin. 

PMID- 24925222
TI  - GNAS is frequently mutated in both low-grade and high-grade disseminated
      appendiceal mucinous neoplasms but does not affect survival.
AB  - We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at
      our institution for GNAS and KRAS mutations in an attempt to correlate mutation
      status with clinicopathological findings and patient survival. GNAS mutations
      (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55
      of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade
      mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a
      signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas
      with a signet ring cell component. All 7 mucinous adenocarcinomas composed of
      pure (>95%) signet ring cells harbored wild-type GNAS. There was no significant
      association between GNAS mutations and sex and age (both with P > .05) or between
      GNAS mutations and individual adverse histologic features including cytologic
      grade, destructive invasion, tumor cellularity, angiolymphatic invasion,
      perineural invasion, and signet ring cells (all with P > .05). KRAS mutations
      were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS-mutated
      disseminated appendiceal mucinous neoplasms more frequently harbored concurrent
      KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018).
      GNAS mutations were not significantly associated with overall survival (both with
      P > .05). Only overall tumor grade was an independent predictor of overall
      survival in the multivariate analysis (P = .01). Our results indicate that GNAS
      mutations are frequently identified in both low-grade and high-grade disseminated
      appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be
      used to distinguish between low-grade from high-grade appendiceal mucinous
      neoplasms.

PMID- 24925223
TI  - Loss of ARID1A expression in colorectal carcinoma is strongly associated with
      mismatch repair deficiency.
AB  - ARID1A is a tumor suppressor gene involved in chromatin remodelling. ARID1A
      mutations and loss of protein expression occur commonly in endometrioid and
      gynecological clear cell carcinoma where they are associated with mismatch repair
      (MMR) deficiency. We assessed ARID1A expression in a large cohort of colorectal
      carcinomas (CRCs). Immunohistochemistry for ARID1A was performed on whole
      sections from 100 CRCs and on 1876 CRCs in tissue microarray format. There was
      complete concordance between the staining on whole slides and tissue microarray
      sections. Loss of staining was found in 110 (5.9%) of 1876 CRCs and was strongly
      associated with older age, right sided location, large size, BRAF V600E mutation,
      MMR deficiency, high histological grade and medullary morphology, (all P < .01).
      There was a trend towards loss of expression being more common in females (P =
      .06). When subclassified by combined BRAF V600E mutation and MMR status, loss of
      ARID1A expression was found most commonly in CRCs with the BRAF V600E mutated,
      MMR- deficient phenotype (58 of 232 cases, 25%, P < .01). In univariate and
      multivariate analysis, loss of ARID1A expression was not associated with overall
      survival-hazard ratio 1.05 (0.68-1.64) and 0.60 (0.24-1.44), respectively. All
      carcinomas arising in patients with known Lynch syndrome (n = 12) were ARID1A
      positive. We conclude that loss of ARID1A expression occurs in a small but
      significant proportion of CRCs where it is strongly correlated with mismatch
      repair deficiency and other clinical and pathological features associated with
      somatic hypermethylation.

PMID- 24925224
TI  - Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal
      zone lymphomas and is useful in the differential diagnosis with follicular
      lymphoma.
AB  - The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of
      specific markers that distinguish them from other low-grade non-Hodgkin B-cell
      lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear
      protein that labels myelomonocytic cells as well as B lymphocytes that localize
      to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in
      a large series of B-cell lymphomas to assess the sensitivity and specificity of
      this antigen for the characterization of MZL. A total of 440 tissue sections
      containing extramedullary B-cell lymphomas and 216 bone marrow biopsies
      containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by
      immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67%
      of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA
      was also infrequently expressed in other B-cell neoplasms including mantle cell
      lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%),
      follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse
      large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all
      bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL
      and one case of MZL. Collectively, these data support the inclusion of MNDA in
      the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those
      in which the differential diagnosis is between low-grade FL and MZL. 

PMID- 24925225
TI  - Forced monogamy in a multiply mating species does not impede colonisation
      success.
AB  - BACKGROUND: The guppy (Poecilia reticulata) is a successful invasive species. It
      is also a species that mates multiply; previous studies have demonstrated that
      this strategy carries fitness benefits. Guppies are routinely introduced to tanks
      and troughs in regions outside their native range for mosquito-control purposes,
      and often spread beyond these initial confines into natural water bodies with
      negative ecological consequences. Here, using a mesocosm set up that resembles
      the containers into which single guppies are typically introduced for mosquito
      control, we ask whether singly-mated females are at a disadvantage, relative to
      multiply-mated females, when it comes to founding a population. Treatments were
      monitored for one year. RESULTS: A key finding was that mating history did not
      predict establishment success, which was 88% in both treatments. Furthermore,
      analysis of behavioural traits revealed that the descendants of singly-mated
      females retained antipredator behaviours, and that adult males showed no decrease
      in courtship vigour. Also, we detected no differences in behavioural variability
      between treatments. CONCLUSIONS: These results suggest that even when denied the
      option of multiple mating, singly-mated female guppies can produce viable
      populations, at least at the founder stage. This may prove to be a critical
      advantage in typical introduction scenarios where few individuals are released
      into enclosed water bodies before finding their way into natural ecosystems.

PMID- 24925226
TI  - The effect of two endogenous retinoids on the mRNA expression profile in human
      primary keratinocytes, focusing on genes causing autosomal recessive congenital
      ichthyosis.
AB  - Retinoids (natural forms and synthetic derivatives of vitamin A) are used as
      therapeutic agents for numerous skin diseases such as keratinization disorders
      (e.g. ichthyoses) and psoriasis. Two endogenous ligands for retinoic acid
      receptors exist, retinoic acid (atRA) and 3,4-didehydroretinoic acid (ddRA). In
      primary human epidermal keratinocytes many transcriptional targets for atRA are
      known, whereas the targets for ddRA are unknown. In an attempt to determine the
      targets, we compared the effect of atRA and ddRA on transcriptional profiles in
      undifferentiated and differentiating human primary keratinocytes. First, as
      expected, many genes were induced or suppressed in response to keratinocyte
      differentiation. Furthermore, the two retinoids affected substantially more genes
      in differentiated keratinocytes (>350) than in proliferating keratinocytes (~20).
      In differentiating keratinocytes markers of cornification were suppressed
      suggesting a de-differentiating effect by the two retinoids. When comparing the
      expression profile of atRA to that of ddRA, no differently regulated genes were
      found. The array analysis also found that a minor number of miRNAs and a large
      number of non-coding transcripts were changed during differentiation and in
      response to the two retinoids. Furthermore, the expression of all, except one,
      genes known to cause autosomal recessive congenital ichthyosis (ARCI) were found
      to be induced by differentiation. These results comprehensively document that
      atRA and ddRA exert similar transcriptional changes in keratinocytes and also add
      new insights into the molecular mechanism influenced by retinoids in the
      epidermis. Furthermore, it suggests which ARCI patients could benefit from
      therapy with retinoids. 

PMID- 24925228
TI  - Examination of the early infection stages of koi herpesvirus (KHV) in
      experimentally infected carp, Cyprinus carpio L. using in situ hybridization.
AB  - Koi herpesvirus (KHV) causes a highly infectious disease afflicting common carp
      and koi, Cyprinus carpio L. Various molecular and antibody-based detection
      methods have been used to elucidate the rapid attachment and dissemination of the
      virus throughout carp tissues, facilitating ongoing development of effective
      diagnostic approaches. In situ hybridization (ISH) was used here to determine the
      target tissues of KHV during very early infection, after infecting carp with a
      highly virulent KHV isolate. Analysis of paraffin-embedded tissues (i.e. gills,
      skin, spleen, kidney, gut, liver and brain) during the first 8 h and following 10
      days post-infection (hpi; dpi) revealed positive signals in skin mucus, gills and
      gut sections after only 1 hpi. Respiratory epithelial cells were positive as
      early as 2 hpi. Viral DNA was also detected within blood vessels of various
      tissues early in the infection. Notable increases in signal abundance were
      observed in the gills and kidney between 5 and 10 dpi, and viral DNA was detected
      in all tissues except brain. This study suggests that the gills and gut play an
      important role in the early pathogenesis of this Alloherpesvirus, in addition to
      skin, and demonstrates ISH as a useful diagnostic tool for confirmation of
      acutely infected carp. 

PMID- 24925227
TI  - Telephone-delivered behavioral intervention among blacks with sleep apnea and
      metabolic syndrome: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Lack of adherence to recommended treatment for obstructive sleep
      apnea remains an ongoing public health challenge. Despite evidence that
      continuous positive airway pressure (CPAP) is effective and improves overall
      quality of life, adherence with the use of CPAP in certain racial/ethnic groups,
      especially blacks, is suboptimal. Evidence indicates that the incidence and
      prevalence of obstructive sleep apnea are higher among blacks, relative to
      whites, and blacks are less likely to adhere to recommended treatment compared
      with other racial/ethnic groups. METHODS: Using a two-arm randomized controlled
      design, this study will evaluate the effectiveness of a culturally and
      linguistically tailored telephone-delivered intervention to promote adherence to
      physician-recommended sleep apnea assessment and treatment among blacks with
      metabolic syndrome, versus an attention-control arm. The intervention is designed
      to foster adherence to recommended sleep apnea care using the stages-of-change
      model. The intervention will be delivered entirely over the telephone.
      Participants in the intervention arm will receive 10 phone calls to address
      challenges and barriers to recommended care. Outcomes will be assessed at
      baseline, and at 6- and 12-months post-randomization. DISCUSSION: This tailored
      behavioral intervention will improve adherence to sleep apnea assessment and
      treatment among blacks with metabolic syndrome. We expect to demonstrate that
      this intervention modality is feasible in terms of time and cost and can be
      replicated in populations with similar racial/ethnic backgrounds. TRIAL
      REGISTRATION: The study is registered at clinicaltrials.gov NCT01946659 (February
      2013).

PMID- 24925229
TI  - Practical considerations when prescribing icodextrin: a narrative review.
AB  - BACKGROUND: Icodextrin is a peritoneal dialysis solution that is commonly used to
      increase ultrafiltration during the long dwell. The other major clinical benefit
      of icodextrin is that it is glucose-sparing, which may help preserve peritoneal
      membrane function. Since it has a different chemical composition than dextrose,
      and with its increasing use, there are several clinical considerations healthcare
      providers must familiarize themselves with prior to prescribing icodextrin.
      SUMMARY: Failure to recognize these special properties of icodextrin can lead to
      adverse events reaching patients. This narrative review explores the hemodynamic,
      metabolic, and idiopathic effects of icodextrin to facilitate the safe use of
      icodextrin in peritoneal dialysis. KEY MESSAGES: Hemodynamic effects include
      hypotension from enhanced ultrafiltration contributing to loss of residual kidney
      function. Metabolic effects include the chemical structure of icodextrin
      interfering with biochemical assays, resulting in misleading glucose readings on
      non-specific glucometers. Idiopathic adverse effects include a diffuse rash and
      sterile peritonitis. It is also important to remember that not all antibiotic
      combinations have undergone stability testing in icodextrin. This narrative
      review will help healthcare providers to confidently prescribe icodextrin to
      maximize its benefit in peritoneal dialysis patients.

PMID- 24925230
TI  - Pharyngeal weakness and upper esophageal sphincter opening in patients with
      unilateral vocal fold immobility.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate pharyngeal strength and upper esophageal
      sphincter opening in patients with unilateral vocal fold immobility (UVFI). STUDY
      DESIGN: Case control study. METHODS: Charts of individuals with UVFI who
      underwent a videofluoroscopic swallow study were reviewed. To exclude confounding
      variables associated with pharyngeal weakness, inclusion was limited to patients
      with iatrogenic and idiopathic UVFI. Data abstracted included patient
      demographics, etiology of UVFI, pharyngeal constriction ratio (PCR), and upper
      esophageal sphincter (UES) opening (UESmax). Data were compared to age/gender
      matched controls with no history of dysphagia or UVFI. Discrete variables were
      analyzed using a chi-square test of independence, and an independent samples t
      test was used to compare the UVFI and control groups (P = 0.05). A one-way
      analysis of variance (ANOVA) was used to compare iatrogenic and idiopathic UVFI
      groups. RESULTS: The mean age of the cohort (n = 25) was 61 (+/-14 SD) years and
      52% was female. The etiologies of UVFI were iatrogenic (n = 17) and idiopathic (n
      = 8). Thirty-eight percent of UVFI patients (n = 25) aspirated compared to 0% of
      controls (P < 0.05). The mean PCR for the UVFI group was 0.14 (+/-0.02) compared
      to 0.06 (+/-.01) for controls (P < 0.05). The mean UESmax for the UVFI group was
      0.82 cm (+/-0.04) compared to 1.0 cm (+/-0.05) for controls (P > 0.05).
      CONCLUSION: Individuals with UVFI of iatrogenic and idiopathic etiologies with
      subjective dysphagia demonstrate objective evidence of pharyngeal weakness. The
      increased prevalence of aspiration in this population may not be solely the
      result of impaired airway protection.

PMID- 24925231
TI  - Localization and speciation of mercury in brown rice with implications for pan
      Asian public health.
AB  - Cultivation of paddy rice for human consumption is a dominant agricultural
      activity throughout Asia. High levels of mercury (Hg) in rice grain pose a
      potential threat to human health, although the extent of risk is dependent on the
      chemical speciation of Hg inside the grain. We have investigated the speciation
      and localization of Hg in three fractions of rice grain (hull, bran, and white
      rice) collected from a Hg-contaminated region in China. On a mass basis, the
      majority of inorganic mercury (IHg) in a rice grain is found in hull and bran.
      However, the majority of the more toxic species methyl mercury (MeHg) is found in
      edible white rice. Our data show that during grain processing, most of the IHg
      (~78%) is eliminated, but the majority of the MeHg remains in the food product
      (~80%). Synchrotron radiation microscopic X-ray fluorescence (SR-MUXRF) mapping
      shows strong localization of Hg at the surface of brown rice grains,
      corresponding to the pericarp and aleurone layer. We infer that this Hg is
      predominantly IHg absorbed from the atmosphere. Based on X-ray absorption near
      edge spectroscopy (XANES) data we propose that IHg in bran is primarily bound to
      cysteine, and is associated with phytochelatins. Consequently, IHg is largely
      immobile and restricted to the outer layers of rice grain. MeHg in bran is
      primarily bound to cysteine and is associated with proteins. However, this MeHg
      cysteine association behaves like a mobile nutrient and is actively transported
      to the endosperm during seed ripening. Concentration of MeHg-cysteine in white
      rice has implications for public health. There is growing evidence for Hg
      contamination of rice throughout Asia due to point and diffuse sources of Hg
      pollution. The magnitude of the associated risk must be quantified through better
      understanding of the localization and speciation of mercury in rice. Our work
      makes an effort to contribute to this understanding. 

PMID- 24925232
TI  - Median nerve T2 assessment in the wrist joints: preliminary study in patients
      with carpal tunnel syndrome and healthy volunteers.
AB  - PURPOSE: To perform a prospective quantitative analysis of median nerve T2 values
      and cross-sectional area (CSA) in patients with carpal tunnel syndrome (CTS) as
      compared to asymptomatic volunteers. MATERIALS AND METHODS: Twelve CTS patients
      with positive nerve conduction results and 12 healthy volunteers (controls) were
      enrolled and underwent axial T2 mapping of the wrist joints. Median nerve T2
      values and CSAs at the distal radioulnar joint, pisiform, and hook of hamate
      levels were compared between the groups. RESULTS: The T2 values at the proximal
      and distal carpal tunnel were higher in the CTS patients than in the controls (P
      < 0.05). The T2 values at the distal radioulnar joint did not differ between the
      groups (P = 0.99). The CSAs of the median nerve at all levels of the carpal
      tunnel were significantly larger in the CTS patients than in the controls (P <
      0.05). CONCLUSION: In conclusion, our study demonstrated that median nerve T2
      assessment is feasible and that T2 assessment may offer functional information
      about the median nerve in the carpal tunnel and has the potential to be a
      promising complementary method for evaluation of CTS patients. A future study
      with larger sample sizes is necessary to investigate the potential effect of
      median nerve T2 assessment to a reliable tool in the diagnosis of CTS.

PMID- 24925233
TI  - The 20-year effort to reduce access to mammography screening: historical facts
      dispute a commentary in Cancer.
AB  - Mammography screening fulfills all requirements for an effective screening test.
      It detects many cancers earlier when they are at a smaller size and earlier
      stage, and it has been demonstrated that this reduces breast cancer deaths in
      randomized controlled trials. When screening is introduced into the population,
      the death rate from breast cancer declines. Nevertheless, scientifically
      unsupported arguments that appear in the medical literature are passed on to the
      public and continue to confuse women and physicians regarding the value of
      screening. Methodologically flawed challenges to mammography have been almost
      continuous since the 1990s. And, as each challenge has been invalidated, a new,
      specious challenge has been raised. The authors of this report address the long
      history of misinformation that has developed in the effort to reduce access to
      screening, and they address the issues raised by commentators concerning their
      recent publication in this journal.

PMID- 24925235
TI  - Editor's preface.

PMID- 24925236
TI  - Long-term retention of kinship recognition established during infancy in the
      domestic dog.
AB  - The ability of the domestic dog to recognise its kin, and to retain this
      information once acquired, was studied in this paper. Dogs were examined for
      their ability to recognise their siblings, offspring to recognise their mother,
      and mothers to recognise their offspring, using a series of two choice tests. The
      results revealed that, at 4-5.5 weeks of age, pups can recognise their siblings
      and their mother, and mothers can recognise their offspring. The preference of
      pups at this age appears to be strongest for their mother. Olfactory cues are
      sufficient for this recognition to take place. At approximately 2 years of age,
      and having been separated from their offspring from 8-12 weeks after their birth,
      mothers were able to recognise their now adult offspring and these adult
      offspring could recognise their mothers. Siblings could only recognise one
      another if they had been living with a sibling (not the test animal). Dogs living
      on their own were unable to recognise their siblings. Thus dogs can recognise
      their kin, retaining this information for a period of two years in the case of
      mother-offspring. It is suggested that mother-offspring and siblings are
      recognised by different mechanisms. 

PMID- 24925237
TI  - Temporal-based kinship recognition: A switch in time saves mine.
AB  - A wide variety of animals show infanticidal responses to conspecific young but
      switch to parental responses at a time that their own young could be expected.
      This widespread, fundamental mechanism of indirect kin recognition has been
      largely ignored in reviews of kin recognition. The present review examines the
      behavioural changes seen in both sexes of biparental vertebrates and
      invertebrates. The sexes may have different qualities of information concerning
      the timing of the arrival of young, typical with internal fertilization, or may
      have similar information, typical with external fertilization. Where the
      information is different the female is usually the one with the more accurate
      information and is more precise in the timing of behavioural change. Males err on
      the side of caution concerning harming their own young and become parental
      earlier than females. Where the information is similar the sexes show
      similarities in the timing of the change. In all cases studied to date, however,
      the changes occur prior to the arrival of their own young. 

PMID- 24925238
TI  - Kin discrimination within honey bee (Apis mellifera) colonies: An analysis of the
      evidence.
AB  - Compelling evolutionary arguments lead to the prediction that honey bee workers
      should discriminate between supersisters and half-sisters within colonies. We
      review the theoretical support for discrimination during swarming, queen rearing,
      feeding, and grooming. A survey of the data that tests whether such
      discrimination takes place shows that, despite substantial effort in a number of
      laboratories, there is no conclusive evidence for intracolony discrimination in
      any of the postulated contexts. The strongest suggestive data is in the critical
      context of queen rearing, but flaws in experimental design or analysis make the
      best available tests inconclusive. We present new data that shows that cues exist
      on which discriminations can be made among adult workers in nestmate recognition
      interactions and in feeding interactions, but our data does not differentiate
      between subfamily recognition and recognition associated with color phenotypes.
      We conclude that while selection may favor discrimination between supersisters
      and half-sisters, as a practical matter such discriminations play no role, or
      only a minor role, in the biology of the honey bee. 

PMID- 24925239
TI  - Differential involvement of right and left hemisphere in individual recognition
      in the domestic chick.
AB  - Right hemisphere advantage in individual recognition (as shown by differences
      between response to strangers and companions) is clear in the domestic chick.
      Chicks using the left eye (and so, thanks to the complete optic decussation,
      predominantly the right hemisphere) discriminate between stranger and companion.
      Chicks using the right eye discriminate less clearly or not at all. The ability
      of left eyed chicks to respond to differences between strangers and companions
      stimuli is associated with a more general ability to detect and respond to
      novelty: this difference between left and right eyed chicks also holds for
      stimuli which are not social partners. The right hemisphere also shows advantage
      in tasks with a spatial component (topographical learning; response to change in
      the spatial context of a stimulus) in the chick, as in humans. Similar
      specialisations of the two hemispheres are also revealed in tests which involve
      olfactory cues presented by social partners. The special properties of the left
      hemisphere are less well established in the chick. Evidence reviewed here
      suggests that it tends to respond to selected properties of a stimulus and to use
      them to assign it to a category; such assignment then allows an appropriate
      response. When exposed to an imprinting stimulus (visual or auditory) a chick
      begins by using right eye or ear (suggesting left hemisphere control), and then
      shifts to the left eye or ear (suggesting right hemisphere control), as exposure
      continues. The left hemisphere here is thus involved whilst behaviour is
      dominated by vigorous response to releasing stimuli presented by an object.
      Subsequent learning about the full detailed properties of the stimulus, which is
      crucial for individual recognition, may explain the shift to right hemisphere
      control after prolonged exposure to the social stimulus. There is a marked sex
      difference in choice tests: females tend to choose companions in tests where
      males choose strangers. It is possible that this difference is specifically
      caused by stronger motivation to sustain social contact in female chicks, for
      which there is extensive evidence. However, sex differences in response to change
      in familiar stimuli are also marked in tests which do not involve social
      partners. Finally, in both sexes there are two periods during development in
      which there age-dependent shifts in bias to use one or other hemisphere. These
      periods (days 3-5 and 8-11) coincide with two major changes in the social
      behaviour of chicks reared by a hen in a normal brood. It is argued that one
      function of these periods is to bring fully into play the hemisphere most
      appropriate to the type of response to, and learning about, social partners which
      is needed at particular points in development. Parallels are discussed between
      the involvement of lateralised processes in the recognition of social partners in
      chicks and humans. 

PMID- 24925240
TI  - Social and individual recognition in rodents: Methodological aspects and
      neurobiological bases.
AB  - What animals know about each other, and how they construct and use knowledge of
      their social world involves at least an ability to recognise different social
      categories. Although much evidence has accumulated that animals are able to
      identify and classify other individuals into different categories, few studies
      have definitively demonstrated true individual recognition, i.e. discrimination
      between individuals on the basis of their idiosyncratic characteristics.
      Furthermore, the neural structures and pathways involved in social and, a
      fortiori, individual recognition have as yet been poorly investigated. This paper
      discusses various methods and measures currently used to assess different forms
      of social categorisations in animals, with special reference to rodents. Recent
      progress concerning the neurobiological bases involved in social recognition is
      also discussed. Finally, integrative perspectives for studying individual
      recognition in the context of social cognition is underlined in relation to
      different approaches investigating rodents' ability to use learned olfactory
      information. 

PMID- 24925241
TI  - Neurobiological correlates of visual and olfactory recognition in sheep.
AB  - This paper describes neurophysiological and behavioural experiments which
      investigate the ability of sheep to recognise different individuals using visual
      and olfactory cues. Behavioural experiments using Y-mazes with back-projected
      images of faces have shown that sheep can distinguish between the faces of sheep
      and humans when the faces are presented in a frontal view although they have more
      difficulty in doing so if the faces are presented in profile, upside down or with
      the eyes obscured. Single-cell electrophysiological recordings made from neurones
      in the temporal cortex have shown that sheep, like non-human primates, have cells
      in this region that code preferentially for facial stimuli and that their
      responses are also diminished or abolished if the faces are presented upside
      down, in profile, or with the eyes obscured. Different sub-populations of cells
      code for faces of similar social and emotional significance. Thus one population
      of cells codes for faces with horns and their responses are also modulated by the
      size of the horns, another population codes for faces of animals of the same
      breed, and particularly familiar animals, and a final population codes for faces
      of humans and dogs. Visual cues from body shape and posture are also important
      for recognition of different classes of individual. Field studies have shown that
      sheep find it difficult to recognise humans approaching them if they change their
      posture to quadrupedal as opposed to a bipedal one. Electrophysiological studies
      have also demonstrated the presence of cells in the temporal cortex which respond
      preferentially to the sight of a human body shape and their activity is
      influenced by body orientation, posture and direction of movement. In some cases
      alterations to the human's appearance can also influence their activity.
      Olfactory recognition studies have used electrophysiological, in vivo sampling
      and behavioural analyses to establish the mechanisms whereby a maternal ewe
      develops the ability to selectively recognise the odour signatures of its own
      lambs within the first few hours of giving birth. Electrophysiological recordings
      from mitral cells in the olfactory bulb have shown that none of them respond
      preferentially to lamb odours pre-partum, when the ewes show no interest in
      lambs, whereas 60% of them do so after ewes have bonded with their lambs. A sub
      population of mitral cells also responds differentially to own and alien lamb
      odours post-partum. Neurochemical studies have shown that lamb odours do not
      evoke transmitter release within the olfactory bulb pre-partum whereas, post
      partum, own lamb odours stimulate release of the intrinsic amino acid
      transmitters, GABA and glutamate whereas both own and alien lamb odours evoke
      equivalent increases in the release of the centrifugal pathway transmitters,
      acetylcholine and nonadrenaline. Overall these experiments provide compelling
      evidence that the sheep, which is after all a social animal, makes use of
      sophisticated visual cues from the face and body and of olfactory cues from the
      body and wool to recognise different individuals. The neural pathways which are
      involved in both of these recognition processes also show remarkable evidence of
      plasticity. However, there appears to be a much closer link between recognition
      and emotional significance demonstrated in the coding strategies employed by the
      neural circuits involved in individual recognition in the sheep brain compared to
      that of a primate and, indeed, they seem to be organised more for identifying a
      small number of different categories of individuals rather than for a large
      number of individuals per se. It is possible therefore that social evolutionary
      pressures to specifically identify large numbers of individuals of similar
      emotional significance has been achieved by weakening the organisational
      influence of affect on coding strategies of cells in the temporal cortex in
      favour of a more extensive feature detection system allowing accurate
      discrimination between a large number of individuals and their expressions under
      a number of different viewing conditions. 

PMID- 24925242
TI  - Brain mechanisms for invariant visual recognition and learning.
AB  - Mechanisms by which the brain could perform invariant recognition of objects
      including faces are addressed neurophysiologically, and then a computational
      model of how this could occur is described. Some neurons that respond primarily
      to faces are found in the macaque cortex in the anterior part of the superior
      temporal sulcus (in which region neurons are especially likely to be tuned to
      facial expression, and to face movement involved in gesture). They are also found
      more ventrally in the TE areas which form the inferior temporal gyrus. Here the
      neurons are more likely to have responses related to the identity of faces. These
      areas project on to the amygdala and orbitofrontal cortex, in which face
      selective neurons are also found. Quantitative studies of the responses of the
      neurons that respond differently to the faces of different individuals show that
      information about the identity of the individual is represented by the responses
      of a population of neurons, that is, ensemble encoding is used. The rather
      distributed encoding (within the class faces) about identity in these sensory
      cortical regions has the advantages of maximising the information in the
      representation useful for discrimination between stimuli, generalisation, and
      graceful degradation. In contrast, the more sparse representations in structures
      such as the hippocampus may be useful to maximise the number of different
      memories stored. There is evidence that the responses of some of these neurons
      are altered by experience so that new stimuli become incorporated in the network,
      in only a few seconds of experience with a new stimulus. It is shown that the
      representation that is built in temporal cortical areas shows considerable
      invariance for size, contrast, spatial frequency and translation. Thus the
      representation is in a form which is particularly useful for storage and as an
      output from the visual system. It is also shown that one of the representations
      which is built is view-in-variant, which is suitable for recognition and as an
      input to associative memory. Another is viewer-centered, which is appropriate for
      conveying information about gesture. It is shown that these computational
      processes operate rapidly, in that in a backward masking paradigm, 20-40 ms of
      neuronal activity in a cortical area is sufficient to support face recognition.
      In a clinical application of these findings, it is shown that humans with ventral
      frontal lobe damage have in some cases impairments in face and voice expression
      identification. These impairments are correlated with and may contribute to the
      problems some of these patients have in emotional and social behaviour. To help
      provide an understanding of how the invariant recognition described could be
      performed by the brain, a neuronal network model of processing in the ventral
      visual system is described. The model uses a multistage feed-forward
      architecture, and is able to learn invariant representations of objects including
      faces by use of a Hebbian synaptic modification rule which incorporates a short
      memory trace (0.5 s) of preceding activity to enable the network to learn the
      properties of objects which are spatio-temporally invariant over this time scale.

PMID- 24925243
TI  - How monkeys see others: Discrimination and recognition of monkeys' shape.
AB  - The two experiments described in this study address the question of the
      perceptual basis of species discrimination and body recognition in monkeys.
      Longtailed macaques (Macaca fascicularis) were trained to discriminate line
      drawings of different monkey bodies. The procedure consisted of a simultaneous
      discrimination between four images under continuous reinforcement. Social
      communication between the test animal and other group members during test
      sessions was almost unrestricted. In the first experiment all monkeys learned,
      within at least 7 sessions, to discriminate one monkey from other monkeys.
      Discrimination was invariant against transformations of size and rotation of the
      stimuli. A preference test for particular features resulted in a graded
      estimation of particular body features. Generalisation to different views of
      facial stimuli was demonstrated. In the second experiment the monkeys had to
      relearn a new association which involved a differentiation of the previously
      shown stimuli. After reaching the learning criterion it was shown that the same
      features as in the previous experiment were evaluated differently. The
      experiments generally support the view that perceptual mechanisms of the signal
      receiver are crucial for individual recognition. Results are discussed in
      contrast to a 'theory of mind' approach in primate cognition. 

PMID- 24925244
TI  - Images of conspecifics as categories to be discriminated by pigeons and chickens:
      Slides, video tapes, stuffed birds and live birds.
AB  - Four experiments investigated the discrimination of images of conspecifics by
      pigeons; in Experiment 1, chickens were also used as subjects, and images of
      allospecifics were also used as discriminative stimuli. In Experiment 1, chickens
      were successfully trained to discriminate slides of pigeons, pictures of one bird
      being positive stimuli and pictures of another bird being negative; and pigeons
      were similarly trained to discriminate slides of chickens. However, an attempt to
      train pigeons to discriminate slides of pigeons only succeeded with one bird out
      of six. Pigeons were slower to learn chicken slides, and chickens were slower to
      learn pigeon slides, than chickens were to learn chicken slides in a previous
      experiment. In Experiment 2, a dishabituation technique was used to demonstrate
      that pigeons readily discriminate individual live pigeons. In Experiment 3, an
      attempt was made to test habituation to life-size moving video images of pigeons,
      but these images did not elicit any natural social responses from the subject
      pigeons. In Experiment 4 pigeons were trained in a discrimination in which the
      objects to be discriminated were two different stuffed pigeons. No pigeon learned
      this discrimination. The experiments give some evidence that chickens are better
      at discriminating images of individuals than pigeons. No single feature seems to
      be sufficient for pigeons to discriminate between conspecifics, but the
      combination of features that is required remains unknown. 

PMID- 24925245
TI  - Olfactory and visual cues in the interaction systems between dogs and children.
AB  - Various studies have established the importance of olfactory cues in the
      relational systems between conspecifics by the canids and humans. The study of
      the behaviour of dogs towards children with clothes impregnated with body odours
      has led to the definition of different functions of olfaction in interspecific
      relational systems. An experimental situation in kennels details the behaviour of
      dogs in response to different combinations of visual and olfactory stimulations
      reproduced with a realistic child dummy. The discussion of the results deals with
      the contingent socio-cognitive abilities of pet dogs and their relational
      strategies based on the integration of different sensory modalities present in
      the 'social' stimulations. 

PMID- 24925246
TI  - The behavioural cues of familiarity during social interactions among human
      adults: A review of the literature and some observations in normal and demented
      elderly subjects.
AB  - The present paper deals with the non-verbal expression of individual recognition
      in normal and pathological populations. In the first part, the literature on non
      verbal communication is surveyed with a selective attention given to
      observational studies comparing encounters between friends and between strangers
      in young adult subjects. To begin with, it is shown that in some cases external
      observers can discriminate above chance level silent films showing interactions
      between familiar and unfamiliar persons. Then, potential cues enabling such a
      performance are searched for by analysis of familiarity effects on interpersonal
      distance, touching gesture, visual and postural orientation, and facial or manual
      movements expressing affiliation or reticence. Finally, these observations are
      discussed in relation to several underlying processes: learning of interaction
      rules, involvement of an affiliative motivational system, and regulation of
      arousal. The problem of assessing the directionality of the familiarity effects
      is also raised. The second part of the paper addresses the issue of non-verbal
      expression of recognition in subjects who show impaired person recognition in the
      verbal modality. A pilot study compares the behaviour of older institutionalised
      women, either normal or suffering from senile dementia of the Alzheimer's type,
      during conversations with a member of the medical team and with another
      unfamiliar person. The methodological problems raised by the planning of the
      experimental situation are discussed. 

PMID- 24925247
TI  - The cognitive approach to familiar face processing in human subjects.
AB  - This paper reviews Bruce and Young's (1986) influential model of face processing,
      as well as its more recent implementation in the form of an interactive
      activation network. The multi-componential structure of the model is explained.
      How this structure can account for empirical effects such as repetition priming,
      semantic priming or face naming difficulties is briefly discussed. It is then
      shown how the model can be applied to the analysis of a typical
      neuropsychological impairment of face processing: prosopagnosia. Finally, the
      intriguing phenomenon of covert face recognition in prosopagnosic patients is
      briefly reviewed. 

PMID- 24925248
TI  - Mental representations in the recognition of conspecific individuals.
AB  - Individual recognition requires that animals form mental representations of the
      properties of conspecifics as well as of the identity of particular conspecifics.
      Gallistel has defined representations as a precise correspondence (an
      isomorphism) between objects and relations in the environment and structure
      preserving systems in the animal's brain. Research on the neural recognition of
      individual conspecifics is examined to check whether the results satisfy part of
      Gallistel's definition. Mental representations are also discussed with reference
      to concept-discrimination experiments which have demonstrated individual
      recognition using slides of conspecifics. Finally, a simple set-theoretical model
      is presented to describe recognition of the idiosyncratic properties of
      conspecifics. 

PMID- 24925249
TI  - The effects of grape seed and colchicine on carbon tetrachloride induced hepatic
      damage in rats.
AB  - This study aims to determine the effects of grape seed and colchicine on carbon
      tetrachloride (CCl4) induced hepatic damage and on some serum biochemical
      parameters. Sixty male Wistar albino rats (200-250 g) were randomly divided into
      six groups (ten rats/group) and included the control group the group were given
      isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group
      treated i.p. injection of CCl4 (1.0 mL/kg b.w) in corn oil twice in the first
      week, Groups 3 and 4 injected with CCl4 as described for group 2 and the rats
      were orally given (100 mg/kg b.w) GSE and i.p. injected (10 MUg/rat) with
      colchicine for four weeks, respectively and groups 5 and 6 were the grape seed
      and colchicine control groups in which rats were orally given grape seed (100
      mg/kg b.w) and i.p. injected with colchicine (10 MUg/rat), respectively.
      Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy
      were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration,
      changes ranging from degenerative to necrotic, increase in connective tissue
      elements, pronounced in portal sites in particular, and infiltration of lymphoid
      series cell observed in the livers of the rats in group 2, treated with CCl4.
      Histological hepatic changes in the rats in group 3 and 4 were similar to those
      in group 2. The levels of serum total protein, albumin and globulin decreased in
      groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT)
      activities increased. The lowest alkaline phosphatase (ALP) activities were in
      groups 4 and 5. We concluded that GSE and colchicine have not sufficient
      ameliorative effects to CCl4 induced acute hepatic damage.

PMID- 24925250
TI  - Enterohemorrhagic Escherichia coli O157 in Libya.

PMID- 24925251
TI  - Enterohaemorrhagic Escherichia coli O157: a current threat requiring advanced
      approaches--author reply.

PMID- 24925253
TI  - Diffusion-weighted imaging thermometry in multiple sclerosis.
AB  - PURPOSE: To prospectively investigate brain temperature using MR diffusion
      weighted imaging thermometry in multiple sclerosis (MS) patients and age-matched
      healthy controls, to examine comparisons of brain temperature between MS patients
      and healthy volunteers, and to examine correlations between brain temperature and
      disease duration and between brain temperature and Expanded Disability Status
      Scale (EDSS) in MS patients. MATERIALS AND METHODS: Thirteen MS patients and 13
      age-matched healthy controls were examined using a 3.0 Tesla MR unit from January
      2011 to February 2013. Brain temperature in each participant was measured using
      diffusion-weighted imaging-based MR thermometry of the lateral ventricles. Group
      comparisons of brain temperature between MS patients and healthy controls were
      performed using the Student's t-test. The determination of correlation between
      brain temperature in MS patients and disease duration, and between brain
      temperature and EDSS were performed using a Pearson's correlation coefficient
      test. For statistical analyses, values of P < 0.05 were considered statistically
      significant. RESULTS: Median brain temperature was 35.81 degrees C (range, 35.06
      37.03 degrees C) in MS patients, and 36.29 degrees C (range, 35.51-37.89 degrees
      C) in healthy controls representing a significant difference (P = 0.020). No
      significant correlation of both between brain temperature and disease duration
      and between brain temperature and EDSS were identified (r/P = -0.382/0.198, 
      0.026/0.933). CONCLUSION: Brain temperature was significantly lower in MS
      patients than in healthy controls, probably representing decreased brain
      metabolism in MS patients.

PMID- 24925252
TI  - Anxiety, depression and behavioral problems among adolescents with recurrent
      headache: the Young-HUNT study.
AB  - BACKGROUND: It is well documented that both anxiety and depression are associated
      with headache, but there is limited knowledge regarding the relation between
      recurrent primary headaches and symptoms of anxiety and depression as well as
      behavioral problems among adolescents. Assessment of co-morbid disorders is
      important in order to improve the management of adolescents with recurrent
      headaches. Thus the main purpose of the present study was to assess the
      relationship of recurrent headache with anxiety and depressive symptoms and
      behavioral problems in a large population based cross-sectional survey among
      adolescents in Norway. METHODS: A cross-sectional, population-based study was
      conducted in Norway from 1995 to 1997 (Young-HUNT1). In Young-HUNT1, 4872
      adolescents aged 12 to 17 years were interviewed about their headache complaints
      and completed a comprehensive questionnaire that included assessment of symptoms
      of anxiety and depression and behavioral problems, i.e. conduct and attention
      difficulties. RESULTS: In adjusted multivariate analyses among adolescents aged
      12-14 years, recurrent headache was associated with symptoms of anxiety and
      depression (OR: 2.05, 95% CI: 1.61-2.61, p < 0.001), but not with behavioral
      problems. A significant association with anxiety and depressive symptoms was
      evident for all headache categories; i.e. migraine, tension-type headache and non
      classifiable headache. Among adolescents aged 15-17 years there was a significant
      association between recurrent headache and symptoms of anxiety and depression
      (OR: 1.64, 95% CI: 1.39-1.93, p < 0,001) and attention difficulties (OR: 1.25,
      95% CI: 1.09-1.44, p =0.001). For migraine there was a significant association
      with both anxiety and depressive symptoms and attention difficulties, while
      tension-type headache was significantly associated only with symptoms of anxiety
      and depression. Non-classifiable headache was associated with attention
      difficulties and conduct difficulties, but not with anxiety and depressive
      symptoms. Headache frequency was significantly associated with increasing
      symptoms scores for anxiety and depressive symptoms as well as attention
      difficulties, evident for both age groups. CONCLUSIONS: The results from the
      present study indicate that both anxiety and depressive symptoms and behavioral
      problems are associated with recurrent headache, and should accordingly be
      considered a part of the clinical assessment of children and adolescents with
      headache. Identification of these associated factors and addressing them in
      interventions may improve headache management.

PMID- 24925254
TI  - In vivo pediatric shoulder muscle volumes and their relationship to 3D strength.
AB  - In the pediatric shoulder, injury and pathology can disrupt the muscle force
      balance, resulting in severe functional losses. As little data exists pertaining
      to in vivo pediatric shoulder muscle function, musculoskeletal data are crucially
      needed to advance the treatment of pediatric shoulder pathology/injury.
      Therefore, the purpose of this study was to develop a pediatric database of in
      vivo volumes for the major shoulder muscles and correlate these volumes with
      maximum isometric flexion/extension, internal/external rotation, and
      abduction/adduction joint moments. A methodology was developed to derive 3D
      shoulder muscle volumes and to divide the deltoid into sub-units with unique
      torque producing capabilities, based on segmentation of three-dimensional
      magnetic resonance images. Eleven typically developing children/adolescents
      (4F/7M, 12.0 +/- 3.2 years, 150.8 +/- 16.7 cm, 49.2 +/- 16.4 kg) participated.
      Correlation and regression analyses were used to evaluate the relationship
      between volume and maximum, voluntary, isometric joint torques. The deltoid
      demonstrated the largest (30.4 +/- 1.2%) and the supraspinatus the smallest (4.8
      +/- 0.5%) percent of the total summed volume of all six muscles evaluated. The
      anterior and posterior deltoid sections were 43.4 +/- 3.9% and 56.6 +/- 3.9% of
      the total deltoid volume. The percent volumes were highly consistent across
      subjects. Individual muscle volumes demonstrated moderate-high correlations with
      torque values (0.70-0.94, p<0.001). This study presents a comprehensive database
      documenting normative pediatric shoulder muscle volume. Using these data a clear
      relationship between shoulder volume and the torques they produce was established
      in all three rotational degrees-of-freedom. This study furthers the understanding
      of shoulder muscle function and serves as a foundation for evaluating shoulder
      injury/pathology in the pediatric/adolescent population.

PMID- 24925255
TI  - Normal masticatory function partially protects the rat mandibular bone from
      estrogen-deficiency induced osteoporosis.
AB  - BACKGROUND/AIM: In a previous study we showed that mandibular alveolar
      (trabecular) bone appears to be less sensitive to estrogen deficiency than the
      proximal tibia spongiosa. We hypothesized that the mechanical loading of the
      alveolar process during mastication may protect the alveolar bone from the
      detrimental effects observed in other skeletal sites. To test this hypothesis we
      compared the effect of ovariectomy on the mandibular alveolar bone and the
      proximal tibia spongiosa of rats fed either a normal (hard) or a soft diet.
      METHODS: Forty six-month-old female Sprague-Dawley rats underwent trans-abdominal
      ovariectomy (OVX) or sham operation (SHAM). Half of the animals received their
      food in the usual form of pellets (hard consistency), while the other half
      received a soft, porridge-like, isocaloric diet of identical composition (soft
      consistency). Micro-computed tomographic histomorphometry was used to evaluate
      the trabecular micro-architecture. A two-factor analysis of variance was used to
      test for effects and interaction of ovariectomy and/or soft diet. RESULTS: OVX
      had a significantly negative effect on the proximal tibia spongiosa (all
      parameters under study except trabecular thickness; p<0.001) and on the
      mandibular alveolar bone (trabecular number and spacing; p<0.05). Soft diet led
      to a further decrease of mandibular BV/TV (p<0.01), trabecular thickness (p<0.05)
      and number (p<0.05), as well as increase of separation (p<0.001). A significant
      interaction was observed between OVX and soft diet concerning the mandibular
      BV/TV, as well as trabecular thickness and spacing (p<0.05). CONCLUSION: Normal
      (hard) diet limited significantly the negative effects of estrogen deficiency on
      mandibular alveolar bone micro-architecture four months after ovariectomy.

PMID- 24925256
TI  - Tailoring 3,3'-dihydroxyisorenieratene to hydroxystilbene: finding a resveratrol
      analogue with increased antiproliferation activity and cell selectivity.
AB  - Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a
      natural carotenoid) based on an isoprene unit retention truncation strategy.
      Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy
      trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem
      sequence, and surfaced as a promising lead molecule in terms of its selective
      antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1
      phase. Additionally, theoretical calculations and cell uptake experiments
      indicate that the unique polymethylation pattern of compound 1 significantly
      induces a conformational change shift out of planarity and increases its cell
      uptake and metabolic stability. The observation should be helpful to rationally
      design resveratrol-inspired antiproliferative agents. 

PMID- 24925257
TI  - Unilateral subarachnoid and intravitreous FLAIR hyperintensities after gadolinium
      enhanced MRI.

PMID- 24925258
TI  - Band-gap manipulations of monolayer graphene by phenyl radical adsorptions: a
      density functional theory study.
AB  - Phenyl radical (Ph) adsorption on monolayer graphene sheets is used to
      investigate the band-gap manipulation of graphene through density functional
      theory. Adsorption of a single Ph on graphene breaks the aromatic pi-bond and
      generates an unpaired electron, which is delocalized to the ortho or para
      position. Adsorption of a second radical at the ortho or para position saturates
      the radical by electron pairing and results in semiconducting graphene.
      Adsorption of a second radical at the ortho position (ortho-ortho pairing) is
      found to be more favorable than adsorption at the para position (ortho-para
      pairing), and the ortho-ortho pairing has stronger effects on band-gap opening
      compared with ortho-para pairing. Adsorption of even numbers of Ph on graphene by
      ortho-ortho and ortho-para pairings, in general, increases the band gap. Our
      study shows promise of band-gap manipulation in monolayer graphene by Ph
      adsorption, leading to potential wider applications of graphene.

PMID- 24925259
TI  - Self-awareness of foot health status in patients with Type 2 diabetes: the
      Fremantle Diabetes Study Phase II.
AB  - AIMS: To determine self-awareness of diabetes-related foot problems and its
      associates in a community-based cohort of people with Type 2 diabetes. METHODS: A
      survey concerning diabetic foot problems was administered to 358 consecutive
      patients with Type 2 diabetes [mean +/- SD age 67.4 +/- 10.8 years, 56.1% males,
      median (interquartile range) diabetes duration 9.0 (3.9-16.8) years] attending
      for detailed clinical, biochemical and questionnaire assessment as part of the
      longitudinal observational Fremantle Diabetes Study Phase II. RESULTS: Compared
      with the 213 patients (59.5%) who considered their feet to be normal, the 145
      (40.5%) who considered their feet to be abnormal were older, had longer diabetes
      duration and were more likely to have sensory neuropathic symptoms and self
      reported poor circulation (P < 0.001). In those who considered their feet to be
      normal, 67.9% had peripheral sensory neuropathy (score >2/8 on the Michigan
      Neuropathy Screening Instrument clinical portion), 9.9% had an ankle-brachial
      index < 0.9, 6.1% had both peripheral sensory neuropathy and an ankle-brachial
      index < 0.90, and 86.9% had one or more features on inspection, such as
      deformity, dry skin, callus and fissures that could facilitate more serious
      complications, despite the majority having had at least one foot examination by a
      healthcare professional in the previous year. CONCLUSIONS: Self-assessment of
      diabetes-related foot problems by patients in the Fremantle Diabetes Study Phase
      II was unreliable. The present data suggest that self-perceived foot health
      should be assessed together with foot examination findings. Intensive education
      and monitoring may be necessary in those who consider their feet to be normal but
      who have neurovascular, structural and/or other precursors of serious foot
      pathology.

PMID- 24925260
TI  - Combined blockade of testicular and locally made androgens in prostate cancer: a
      highly significant medical progress based upon intracrinology.
AB  - Recently two drugs, namely the antiandrogen MDV-3100 and the inhibitor of 17alpha
      hydroxylase abiraterone have been accepted by the FDA for the treatment of
      castration-resistant prostate cancer (CRPC) with or without previous
      chemotherapy, with a prolongation of overall survival of 2.2-4.8 months. While
      medical (GnRH agonist) or surgical castration reduces the serum levels of
      testosterone by about 97%, an important concentration of testosterone and
      dihydrotestosterone remains in the prostate and activates the androgen receptor
      (AR), thus offering an explanation for the positive data obtained in CRPC. In
      fact, explanation of the response observed with MDV-3100 or enzalutamide in CRPC
      is essentially a blockade of the action or formation of intraprostatic androgens.
      In addition to the inhibition of the action or formation of androgens made
      locally by the mechanisms of intracrinology, increased AR levels and AR mutations
      can be involved, especially in very advanced disease. Future developments look at
      more efficient inhibitors of the action or formation of intraprostatic androgens
      and starting treatment earlier when blockade of androgens can exert long-term
      control and even cure prostate cancer treated at a stage before the appearance of
      metastases. This article is part of a Special Issue entitled 'Essential role of
      DHEA'. 

PMID- 24925263
TI  - Acute hyperammonemia and systemic inflammation is associated with increased
      extracellular brain adenosine in rats: a biosensor study.
AB  - Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and
      intracranial hypertension. These complications are thought to be mediated by
      hyperammonemia and inflammation leading to altered brain metabolism. As increased
      levels of adenosine degradation products have been found in brain tissue of
      patients with ALF we investigated whether hyperammonemia could induce adenosine
      release in brain tissue. Since adenosine is a potent vasodilator and modulator of
      cerebral metabolism we furthermore studied the effect of adenosine receptor
      ligands on intracranial pressure (ICP) and cerebral blood flow (CBF). We measured
      the adenosine concentration with biosensors in rat brain slices exposed to
      ammonia and in a rat model with hyperammonemia and systemic inflammation.
      Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the
      cortical adenosine concentration up to 18 uM in brain slices. In vivo recordings
      showed a tendency towards increased adenosine levels in rats with hyperammonemia
      and systemic inflammation compared to a control group (3.7 +/- 0.7 vs. 0.8 +/-
      0.2 uM, P = 0.06). This was associated with a significant increase in ICP and
      CBF. Intervention with the non-selective adenosine receptor antagonist
      theophyllamine, the A2A receptor antagonist ZM241385, or the A1 receptor agonist
      N6-Cyclopentyladenosine did not reduce ICP or CBF. In conclusion, our results
      show that the adenosine concentration in cortex increases during exposure to
      ammonia, and is associated with a rise in intracranial pressure and cerebral
      perfusion. However adenosine receptor antagonism/agonism did not reduce the ICP
      or CBF which indicates that adenosine may not be of direct importance for these
      cerebral complications in ALF. 

PMID- 24925261
TI  - sigma-1 Receptor Inhibition of ASIC1a Channels is Dependent on a Pertussis Toxin
      Sensitive G-Protein and an AKAP150/Calcineurin Complex.
AB  - ASIC1a channels play a major role in various pathophysiological conditions
      including depression, anxiety, epilepsy, and neurodegeneration following ischemic
      stroke. Sigma-1 (sigma-1) receptor stimulation depresses the activity of ASIC1a
      channels in cortical neurons, but the mechanism(s) by which sigma-1 receptors
      exert their influence on ASIC1a remains unknown. Experiments were undertaken to
      elucidate the signaling cascade linking sigma-1 receptors to ASIC1a channels.
      Immunohistochemical studies showed that sigma-1 receptors, ASIC1a and A-kinase
      anchoring peptide 150 colocalize in the plasma membrane of the cell body and
      processes of cortical neurons. Fluorometric Ca(2+) imaging experiments showed
      that disruption of the macromolecular complexes containing AKAP150 diminished the
      effects of the sigma-1 on ASIC1a, as did application of the calcineurin
      inhibitors, cyclosporin A and FK-506. Moreover, whole-cell patch clamp
      experiments showed that sigma-1 receptors were less effective at decreasing
      ASIC1a-mediated currents in the presence of the VIVIT peptide, which binds to
      calcineurin and prevents cellular effects dependent on AKAP150/calcineurin
      interaction. The coupling of sigma-1 to ASIC1a was also disrupted by
      preincubation of the neurons in the G-protein inhibitor, pertussis toxin (PTX).
      Taken together, our data reveal that sigma-1 receptor block of ASIC1a function is
      dependent on activation of a PTX-sensitive G-protein and stimulation of AKAP150
      bound calcineurin.

PMID- 24925262
TI  - Modifications of diflunisal and meclofenamate carboxyl groups affect their
      allosteric effects on GABAA receptor ligand binding.
AB  - Gamma-aminobutyric acid type A receptors (GABAAR) are allosterically modulated by
      the nonsteroidal anti-inflammatory drugs diflunisal and fenamates. The carboxyl
      group of these compounds is charged at physiological pH and therefore penetration
      of the compounds into the brain is low. In the present study we have transformed
      the carboxyl group of diflunisal and meclofenamate into non-ionizable functional
      groups and analyzed the effects of the modifications on stimulation of
      [(3)H]muscimol binding and on potentiation of gamma-aminobutyric acid-induced
      displacement of 4'-ethenyl-4-n-[2,3-(3)H]propylbicycloorthobenzoate. N-Butylamide
      derivative of diflunisal modulated radioligand binding with equal or higher
      potency than the parent compound, while diflunisalamide showed reduced allosteric
      effect as compared to diflunisal. Amide derivative of meclofenamate equally
      affected radioligand binding parameters, while both diflunisal and meclofenamate
      methyl esters were less active than the parent compounds. Our study clearly
      demonstrates that an intact carboxyl group in diflunisal and meclofenamate is not
      indispensable for their positive GABAAR modulation. Further derivatization of the
      compound might yield compounds with higher selectivity for GABAARs that could be
      utilized in drug development. 

PMID- 24925264
TI  - The ecology of ticks and epidemiology of tick-borne viral diseases.
AB  - A number of tick-borne diseases of humans have increased in incidence and
      geographic range over the past few decades, and there is concern that they will
      pose an even greater threat to public health in future. Although global warming
      is often cited as the underlying mechanism favoring the spread of tick-borne
      diseases, climate is just one of many factors that determine which tick species
      are found in a given geographic region, their population density, the likelihood
      that they will be infected with microbes pathogenic for humans and the frequency
      of tick-human contact. This article provides basic information needed for
      microbiologists to understand the many factors that affect the geographic range
      and population density of ticks and the risk of human exposure to infected ticks.
      It first briefly summarizes the life cycle and basic ecology of ticks and how
      ticks and vertebrate hosts interact, then reviews current understanding of the
      role of climate, sociodemographic factors, agricultural development and changes
      in human behavior that affect the incidence of tick-borne diseases. These
      concepts are then illustrated in specific discussions of tick-borne encephalitis
      and Crimean-Congo hemorrhagic fever. 

PMID- 24925265
TI  - Estimation of the ancestral effective population sizes of African great apes
      under different selection regimes.
AB  - Reliable estimates of ancestral effective population sizes are necessary to
      unveil the population-level phenomena that shaped the phylogeny and molecular
      evolution of the African great apes. Although several methods have previously
      been applied to infer ancestral effective population sizes, an analysis of the
      influence of the selective regime on the estimates of ancestral demography has
      not been thoroughly conducted. In this study, three independent data sets under
      different selective regimes were used were composed to tackle this issue. The
      results showed that selection had a significant impact on the estimates of
      ancestral effective population sizes of the African great apes. The inference of
      the ancestral demography of African great apes was affected by the selection
      regime. The effects, however, were not homogeneous along the ancestral
      populations of great apes. The effective population size of the ancestor of
      humans and chimpanzees was more impacted by the selection regime when compared to
      the same parameter in the ancestor of humans, chimpanzees and gorillas. Because
      the selection regime influenced the estimates of ancestral effective population
      size, it is reasonable to assume that a portion of the discrepancy found in
      previous studies that inferred the ancestral effective population size may be
      attributable to the differential action of selection on the genes sampled. 

PMID- 24925266
TI  - A biocomposite of collagen nanofibers and nanohydroxyapatite for bone
      regeneration.
AB  - This work aims to design a synthetic construct that mimics the natural bone
      extracellular matrix through innovative approaches based on simultaneous type I
      collagen electrospinning and nanophased hydroxyapatite (nanoHA) electrospraying
      using non-denaturating conditions and non-toxic reagents. The morphological
      results, assessed using scanning electron microscopy and atomic force microscopy
      (AFM), showed a mesh of collagen nanofibers embedded with crystals of HA with
      fiber diameters within the nanometer range (30 nm), thus significantly lower than
      those reported in the literature, over 200 nm. The mechanical properties,
      assessed by nanoindentation using AFM, exhibited elastic moduli between 0.3 and 2
      GPa. Fourier transformed infrared spectrometry confirmed the collagenous
      integrity as well as the presence of nanoHA in the composite. The network
      architecture allows cell access to both collagen nanofibers and HA crystals as in
      the natural bone environment. The inclusion of nanoHA agglomerates by
      electrospraying in type I collagen nanofibers improved the adhesion and metabolic
      activity of MC3T3-E1 osteoblasts. This new nanostructured collagen-nanoHA
      composite holds great potential for healing bone defects or as a functional
      membrane for guided bone tissue regeneration and in treating bone diseases. 

PMID- 24925267
TI  - The function of multiple ejaculations in bitterling.
AB  - In some taxa, males perform multiple ejaculations, which may function in sperm
      competition or in maintaining a baseline density of spermatozoa in the female
      reproductive tract to ensure fertilization, a process that has been termed
      'topping up'. We investigated the function of multiple ejaculations in two
      species of bitterling, the European bitterling (Rhodeus amarus) and Chinese rose
      bitterling (Rhodeus ocellatus). Bitterling oviposit in living freshwater mussels,
      with fertilization taking place within the mussel gill cavity. Thus, although
      fertilization is external, the mussel is analogous to the female reproductive
      tract in an internally fertilizing species. We measured the frequency of
      ejaculations and mussel inspections by individual males of two bitterling species
      in 28 replicated mesocosms and examined focal male responses to rival
      ejaculations and the presence of females in spawning condition. We used a model
      of ejaculatory behaviour to simulate the temporal abundance of spermatozoa in
      mussels. Male R. amarus exhibited high rates of ejaculation and inspection of the
      siphons of mussels and increased their ejaculation rate in response to the
      presence of females in spawning condition. Rhodeus ocellatus showed lower overall
      rates of ejaculation, but significantly elevated ejaculation rate in response to
      rival ejaculations. The ejaculatory strategy of R. amarus is one that maintains a
      minimum level of spermatozoa in mussels, which is elevated when the probability
      of oviposition increases. In contrast, R. ocellatus engages more directly in
      sperm competition with rivals. We discuss these results in the context of the
      function of multiple ejaculations and male mating tactics.

PMID- 24925268
TI  - Development and validation of an LC-MS/MS method for the determination of
      mesalazine in beagle dog plasma and its application to a pharmacokinetic study.
AB  - A simple, specific and sensitive LC-MS/MS method was developed and validated for
      the determination of mesalazine in beagle dog plasma. The plasma samples were
      prepared by protein precipitation, then the separation of the analyte was
      achieved on a Waters Spherisorb C6 column (150 * 4.6 mm, 5 um) with a mobile
      phase consisting of 0.2% formic acid in water-methanol (20:80, v/v). The flow
      rate was set at 1.0 mL/min with a split ratio of 3:2. Mass spectrometric
      detection was achieved by a triple-quadrupole mass spectrometer equipped with an
      electrospray source interface in positive ionization mode. Quantitation was
      performed using selected reaction monitoring of precursor-product ion transitions
      at m/z 154 -> m/z 108 for mesalazine and m/z 285 -> m/z 193 for diazepam
      (internal standard). The linear calibration curve of mesalazine was obtained over
      the concentration range 50-30,000 ng/mL. The matrix effect of mesalazine was
      within +/-9.8%. The intra- and inter-day precisions were <7.9% and the accuracy
      (relative error) was within +/-3.5%. The validated method was successfully
      applied to investigate the pharmacokinetics of mesalazine in healthy beagle dogs
      after rectal administration of mesalazine suppository.

PMID- 24925269
TI  - The membrane proteome of Medicago truncatula roots displays qualitative and
      quantitative changes in response to arbuscular mycorrhizal symbiosis.
AB  - Arbuscular mycorrhizal (AM) symbiosis that associates roots of most land plants
      with soil-borne fungi (Glomeromycota), is characterized by reciprocal nutritional
      benefits. Fungal colonization of plant roots induces massive changes in cortical
      cells where the fungus differentiates an arbuscule, which drives proliferation of
      the plasma membrane. Despite the recognized importance of membrane proteins in
      sustaining AM symbiosis, the root microsomal proteome elicited upon mycorrhiza
      still remains to be explored. In this study, we first examined the qualitative
      composition of the root membrane proteome of Medicago truncatula after microsome
      enrichment and subsequent in depth analysis by GeLC-MS/MS. The results obtained
      highlighted the identification of 1226 root membrane protein candidates whose
      cellular and functional classifications predispose plastids and protein synthesis
      as prevalent organelle and function, respectively. Changes at the protein
      abundance level between the membrane proteomes of mycorrhizal and nonmycorrhizal
      roots were further monitored by spectral counting, which retrieved a total of 96
      proteins that displayed a differential accumulation upon AM symbiosis. Besides
      the canonical markers of the periarbuscular membrane, new candidates supporting
      the importance of membrane trafficking events during mycorrhiza
      establishment/functioning were identified, including flotillin-like proteins. The
      data have been deposited to the ProteomeXchange with identifier PXD000875.
      BIOLOGICAL SIGNIFICANCE: During arbuscular mycorrhizal symbiosis, one of the most
      widespread mutualistic associations in nature, the endomembrane system of plant
      roots is believed to undergo qualitative and quantitative changes in order to
      sustain both the accommodation process of the AM fungus within cortical cells and
      the exchange of nutrients between symbionts. Large-scale GeLC-MS/MS proteomic
      analysis of the membrane fractions from mycorrhizal and nonmycorrhizal roots of
      M. truncatula coupled to spectral counting retrieved around one hundred proteins
      that displayed changes in abundance upon mycorrhizal establishment. The symbiosis
      related membrane proteins that were identified mostly function in
      signaling/membrane trafficking and nutrient uptake regulation. Besides extending
      the coverage of the root membrane proteome of M. truncatula, new candidates
      involved in the symbiotic program emerged from the current study, which pointed
      out a dynamic reorganization of microsomal proteins during the accommodation of
      AM fungi within cortical cells.

PMID- 24925271
TI  - Effects of grouping and isolation on feeding, food conversion and energy
      expenditure of domestic chicks.
AB  - At ambient temperatures of 25-30 degrees C, domestic chicks gained more weight
      between 6 and 10 days of age when kept in groups of three than in isolation. This
      difference in growth rate, which was not affected by variation in social
      environment before testing, was due to a difference in food conversion efficiency
      only, and not to one in food intake. The only evidence of social enhancement of
      feeding was a temporary increase in feeding activity (but not food intake) shown
      by grouped chicks previously kept in isolation. The consistent difference in food
      conversion between grouped and isolated chicks was not due to differences in
      activity levels, digestibility, emotionality or stress, but was associated with a
      difference in metabolic heat production, or heat loss. Although there was little
      evidence of huddling by grouped chicks, their heat production was lower than that
      of isolates at ambient temperatures of 20 and 25 degrees C, but not at 30 and 35
      degrees C; and the difference in food conversion efficiency disappeared at 35
      degrees C. It is concluded that isolates lack the opportunities that grouped
      chicks have for behavioral thermoregulation, but that all chicks achieve equal
      status energetically when the ambient temperature lies within or near the zone of
      minimal metabolic rate. 

PMID- 24925272
TI  - Temporal pattern of motor activity of chicks during the early posthatching
      period.
AB  - The motor activity of domestic chicks was continuously recorded in running-wheels
      to ascertain whether it exhibits predictable temporal variations during the first
      3-4 days after hatching. As recorded in constant light and several different
      temperatures, this activity was characterized by a general increment after the
      first day, by irregular fluctuations over intervals of a few hours, and by
      regular, near 24-h cycles commencing after an initial period of variable
      activity. The phase pattern of the cycles of normally hatching chicks correlated
      consistently with posthatching age. Artificially advancing and delaying emergence
      from the shell shifted the phases accordingly, thus indicating that the phase
      pattern, rather than being developmentally scheduled, was determined by initial
      light exposure and, perhaps, slight temperature change at the time of shell
      emergence. The cycles, indicative of a circadian rhythm, provide a prospective
      basis for predicting variations in other aspects of behaviour. 

PMID- 24925270
TI  - The effects of the mediterranean diet on biomarkers of vascular wall inflammation
      and plaque vulnerability in subjects with high risk for cardiovascular disease. A
      randomized trial.
AB  - BACKGROUND: Adherence to the Mediterranean diet (MD) is associated with reduced
      morbidity and mortality due to cardiovascular disease. However, how the MD exerts
      its effects is not fully known. AIM: To assess the 12-month effects of two
      enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to
      atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED
      (Prevencion con Dieta Mediterranea) study. METHODS: A total of 164 participants
      at high risk for cardiovascular disease were randomized into three diet groups:
      MD supplemented with 50mL/d of extra virgin olive oil (MD+EVOO) or 30 g/d of nuts
      (MD+Nuts) and a low-fat diet. Changes in classical cardiovascular risk factors,
      inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured
      after 12 months of intervention. RESULTS: Compared to participants in the low-fat
      diet group, those receiving MD+EVOO and MD+Nuts showed a higher decrease in
      systolic (6mmHg) and diastolic (3mmHg) blood pressure (P = 0.02; both), as well
      as a reduction of 10% and 8% in LDL-cholesterol (P = 0.04), respectively.
      Patients in the MD+Nuts group showed a significant reduction of 34% in CD40
      expression on monocyte surface compared to low-fat diet patients (P = 0.03). In
      addition, inflammatory biomarkers related to plaque instability such as C
      reactive protein and interleukin-6 were reduced by 45% and 35% and 95% and 90% in
      the MD+EVOO and MD+Nuts groups, respectively (P<0.05; all) compared to the low
      fat diet group. Likewise, sICAM and P-selectin were also reduced by 50% and 27%,
      respectively in the MD+EVOO group (P = 0.04) and P-selectin by 19% in MD+Nuts
      group (P = 0.04) compared to the low-fat diet group. CONCLUSIONS: Adherence to
      the MD is associated with an increase in serum markers of atheroma plaque
      stability which may explain, at least in part, the protective role of MD against
      ischemic heart disease. TRIAL REGISTRATION: www.controlled-trials.com
      ISRCTN35739639.

PMID- 24925273
TI  - Auditory stimulus intensity and the neonatal approach response of domestic chicks
      (Gallus gallus).
AB  - Three experiments were performed to investigate the neonatal approach response of
      domestic chicks and its behavioural accompaniments to three intermittent auditory
      stimulus intensities (62, 67, and/or 75 db) and a baseline condition. Chicks from
      a sample of the Cornell Randombred population were tested at 24, 48, 72, 96, 120,
      and/or 144 h of age. The results indicated that louder auditory stimulus
      intensities are generally approached more rapidly. Also, more snuggling and
      contentment peeping and less orientation away and leaving the goal area occured
      at higher levels of auditory stimulus intensity. Pecking scores increased with
      increasing age. Behaviours, other than approach speed, were typically more
      sensitive to changes in chick respositivity. 

PMID- 24925274
TI  - Discriminatory approach to auditory stimuli in Guinea fowl (Numida meleagris)
      after hyperstriatal/hippocampal brain damage.
AB  - Guinea fowl were trained to approach, feed and retreat from a food dish after
      hearing a species-specific food-trill. An ethogram including approach, search,
      locomotion and tension behaviour was recorded before and after operation for a
      training and a test regime of variations of the natural calls and other sounds.
      Experimental groups consisted of shamcontrols and birds with lesions in the
      hyperstriatum/hippocampus anterior and posterior to the anterior commissure. Both
      the 'anterior' and 'posterior' groups showed impaired recognition of the stimulus
      variations as shown by increases of approach by the posterior group and of search
      behaviour by both lesion groups. The long approach of the posterior group was
      followed by a long period of arousal (high tension). This was more quickly
      habituated in the anterior group (search behaviour changed to low tension). It is
      hypothesised that in the anterior group, where activation is followed by a
      disengagement, there may have been changes in thresholds for matching learned
      specifications with new sensory input. The more generalised approach responses of
      the posterior group may show an impairment of the rules for the selection of
      input. 

PMID- 24925275
TI  - Food recruitment strategies of the ants Myrmica sabuleti and Myrmica ruginodis.
AB  - The food-gathering systems of Myrmica sabuleti and Myrmica ruginodis are analysed
      and compared to those, previously described, of M. rubra and M. scabrinodis.
      Workers of the two species studied in this paper collect pure water or small dead
      prey without actively recruiting congeners. Collecting ants of M. ruginodis lay
      down a trail pheromone from their poison gland only when returning to the nest,
      while foragers of M. sabuleti deposit a trail on their way both to the nest and
      back to the food but almost only in darkness. Collecting ants of both species are
      not followed by the few workers which, excited by them in the nest, individually
      reach the food. In the two species studied, an active recruitment of workers
      occurs when a large dead prey or a source of sugared water is presented to a
      colony. After having deposited their trail on their way to the nest, recruiting
      ants 'invite', by tactile signals, congeners to leave the nest. Then the
      recruiting ants return to the food, laying down their attractive Dufour's gland
      content along distances varying with the species and the food stimuli considered.
      Recruiting ants of M. ruginodis generally emit their Dufour's gland secretion
      along longer distances than M. sabuleti foragers, after which they secrete
      nothing more, while M. sabuleti workers go on their way to the food laying down
      their trail substance again. The food-gathering technique of the two species
      studied includes group recruitment, performed on longer distances in M. ruginodis
      than in M. sabuleti, followed by mass recruitment. The number of ants finally
      recruited onto food is generally excessive in M. ruginodis, and in M. sabuleti
      the site is only just saturated. A comparison of these food-collection techniques
      with those of different species of Myrmica, together with a chemical and an
      ethological study of these species' pheromones would provide information for a
      better understanding of these species' ecology, as well as taxonomic and
      phylogenetic positions. 

PMID- 24925276
TI  - Wheel-running behavior in 12 species of muroid rodents.
AB  - The objective of this research was to describe the levels and periodicity of
      wheel running in 12 species of muroid rodents in order that comparisons could be
      made among different measures of activity in a variety of species. Six males from
      each species (Peromyscus polionotus, P. eremicus, P. leucopus, P. maniculatus, P.
      gossypinus, Microtus pennysylvanicus, M. montanus, M. canicaudus, M. ochrogaster,
      Calomys callos us, Onychomys leucogaster, and Mus musculus) were tested in
      running wheels for 14 days, with the amount of running recorded hourly. There
      were significant species differences in amount of wheel running, with Peromyscus
      generally running more than Microtus. All species displayed marked nocturnality.
      Thus, Peromyscus display consistent nocturnality both across species, and for
      various behavioral patterns measured using a variety of methods. By contrast,
      Microtus display a nocturnal pattern of wheel running, but not of eating,
      drinking, and various other behavioral patterns. These differences appear to
      reflect adaptations related to habit and diet. 

PMID- 24925277
TI  - A dark-light emergence test: Study at two times of the nycthemeral cycle in four
      and twelve-week-old rats.
AB  - The latency to emerge from a darkened compartment to a lighted one was measured
      twice daily in 4-and 12-week-old rats. The test was repeated on three consecutive
      days: at 20.00 h on the first day, at 12.00 h and 20.00 h on the second day, and
      at 12.00 h and 20.00 h on the third day. The latencies of the older rats were
      consistently longer than those of the younger ones. While the time of day had no
      influence on the 4-week-old rats performances, latencies of the 12-week-old rats
      were considerably longer at 20.00 h than at 12.00 h. 

PMID- 24925282
TI  - Antibiotic prophylaxis for endoscopic retrograde chlangiopancreatography
      increases the detection rate of drug-resistant bacteria in bile.
AB  - BACKGROUND: No consensus has yet been reached regarding the utility of antibiotic
      prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP). However,
      there has been little discussion of potential adverse effects of antibiotic use.
      This study investigated the impact of antibiotic prophylaxis on overall levels of
      bacterial infiltration of the biliary tract and the prevalence of drug-resistance
      among that population. METHODS: Ninety-three patients, from whom intraoperative
      bile samples were collected after performing ERCP, were assigned to either an
      antibiotic-prophylaxis group (AP, n = 58) or a no-antibiotic-prophylaxis group
      (NAP, n = 35). Detection rates of biliary bacteria and antibiotic resistance were
      determined for each group. Multivariate analysis was also performed to identify
      risk factors for the development of drug-resistant biliary bacteria. RESULTS: The
      bile contamination rate was 37.1% for the NAP group and 55.2% for the AP group (P
      = 0.09). Drug-resistant bacteria were found in 5.7% of the NAP group and 29.3% of
      the AP group (P = 0.006). Biliary drainage and antibiotic prophylaxis for ERCP
      were identified as risk factors for the presence of drug-resistant bacteria.
      CONCLUSION: Administration of antibiotic prophylaxis prior to ERCP can be a risk
      factor for the selection of drug-resistant bacteria in the biliary tract.

PMID- 24925284
TI  - Use of kinematic algorithms to distinguish people with chronic non-specific low
      back pain from asymptomatic subjects: a validation study.
AB  - OBJECTIVE: To determine whether kinematic algorithms can distinguish subjects
      with chronic non-specific low back pain from asymptomatic subjects and subjects
      simulating low back pain, during trunk motion tasks. DESIGN: Comparative cohort
      study. SUBJECTS: A total of 90 subjects composed 3 groups; 45 chronic non
      specific low back pain patients in the CLBP group; 45 asymptomatic controls
      people in the asymptomatic controls group. 20/45 subjects from the asymptomatic
      controls group composed the CLBP simulators group as well. METHOD: During
      performance of 7 standardized trunk motion tasks 6 spinal segments from the
      kinematic spine model were recorded by 8 infrared cameras. Two logit scores, for
      range of motion and speed, were used to investigate differences between the
      groups. Group allocation based on logit scores was also calculated, allowing the
      assessment of sensitivity and specificity of the algorithms. RESULTS: For the 90
      subjects (pooled data), the logit scores for range of motion and speed
      demonstrated highly significant differences between groups (p < 0.001). The logit
      score means and standard deviation (SD) values in the asymptomatic group (n = 45)
      and chronic non-specific low back pain group (n = 45), respectively, were -1.6
      (SD 2.6) and 2.8 (SD 2.8) for range of motion and -2.6 (SD 2.5) and 1.2 (SD 1.9)
      for speed. The sensitivity and specificity (n = 90) for logit score for range of
      motion were 0.80/0.82 and for logit score for speed were 0.80/0.87, respectively.
      CONCLUSION: These results support the validity of using 2 movement algorithms,
      range of motion and speed, to discriminate asymptomatic subjects from those with
      low back pain. However, people simulating low back pain cannot be distinguished
      from those with real low back pain using this method.

PMID- 24925283
TI  - Prolonged ampakine exposure prunes dendritic spines and increases presynaptic
      release probability for enhanced long-term potentiation in the hippocampus.
AB  - CX 546, an allosteric positive modulator of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid-type ionotropic glutamate receptors (AMPARs), belongs to
      a drug class called ampakines. These compounds have been shown to enhance long
      term potentiation (LTP), a cellular model of learning and memory, and improve
      animal learning task performance, and have augmented cognition in
      neurodegenerative patients. However, the chronic effect of CX546 on synaptic
      structures has not been examined. The structure and integrity of dendritic spines
      are thought to play a role in learning and memory, and their abnormalities have
      been implicated in cognitive disorders. In addition, their structural plasticity
      has been shown to be important for cognitive function, such that dendritic spine
      remodeling has been proposed as the morphological correlate for LTP. Here, we
      tested the effect of CX546 on dendritic spine remodeling following long-term
      treatment. We found that, with prolonged CX546 treatment, organotypic hippocampal
      slice cultures showed a significant reduction in CA3-CA1 excitatory synapse and
      spine density. Electrophysiological approaches revealed that the CA3-CA1
      circuitry compensates for this synapse loss by increasing synaptic efficacy
      through enhancement of presynaptic release probability. CX546-treated slices
      showed prolonged and enhanced potentiation upon LTP induction. Furthermore,
      structural plasticity, namely spine head enlargement, was also more pronounced
      after CX546 treatment. Our results suggest a concordance of functional and
      structural changes that is enhanced with prolonged CX546 exposure. Thus, the
      improved cognitive ability of patients receiving ampakine treatment may result
      from the priming of synapses through increases in the structural plasticity and
      functional reliability of hippocampal synapses. 

PMID- 24925285
TI  - Permanent twelfth nerve palsy secondary to C0 and C1 fracture in patient with
      craniocervical pneumatisation.
AB  - INTRODUCTION: Craniocervical pneumatisation of both occiput and upper cervical
      vertebrae is extremely rare. Although it was stated that hyperpneumatisation can
      lead to fracture, only few cases of such injuries have been reported. Generally,
      craniocervical fractures represent a small number of cervical spine injuries and
      they are usually caused by high-energy trauma and can be associated with lower
      cranial nerves palsy. CASE REPORT: We present here a case of healthy man with
      mostly left sided pneumatisation of occiput and C1 who suffered from fractures of
      occipital condyle and posterior arch of C1 associated with permanent hypoglossal
      nerve injury. Both fractures were stable and he was treated conservatively with a
      rigid collar. CONCLUSION: At follow-up, the patient reported no pain and no
      restriction in head movement. Total hypoglossal nerve palsy remained unchanged.
      Conservative treatment is a method of choice in such cases.

PMID- 24925286
TI  - Estimation of sagittal pelvic orientation from frontal standard radiograph using
      the sacral-femoral-pubic angle: feasibility study in the pediatric population.
AB  - PURPOSE: Pelvic tilt is usually measured on a full spine sagittal view. The
      sacral-femoral-pubic angle (SFP) has been previously described as a reproducible
      method to estimate pelvic tilt on a pelvis AP view. The aim of our study is to
      determine the reliability of the extrapolated pelvic tilt (ePT) using the SFP
      angle in the pediatric population. METHODS: We selected 240 full spine X-rays in
      our pediatric imaging database. The cohort was equally distributed according
      gender and age. The following parameters were measured: SFP angle on the AP view,
      pelvic tilt (PT), pelvic incidence (PI) and sacral slope (SS) on the sagittal
      view. Concordance between the measured pelvic tilt (mPT) and the calculated (ePT)
      value of PT was tested by a correlation test. Intra- and inter-observer
      reliability was tested for each parameter using ANOVA. RESULTS: Our cohort
      included 240 children aged from 1 to 20 years (mean age 10.7 years). Mean SFP
      angle was 68.98 degrees  +/- 6.8, mPT was 6.67 degrees  +/- 8.56, ePT was 6.04
      degrees  +/- 6.79. The mean PI (45.04 degrees  +/- 11.09) and SS (38.63 degrees 
      +/- 8.12) were comparable to previously published pediatric data according to age
      groups. Intra- and inter-observer reliability showed acceptable correlation.
      Concordance between mPT and ePT was higher in older children (patients >10
      years). CONCLUSIONS: Estimated value of pelvic tilt using the SFP angle showed
      acceptable correlation to the pelvic tilt measured on sagittal view of the pelvis
      in children over 10 years. However, correlation rates were lower than previous
      publication in adult population. This simple method could accurately estimate the
      pelvic orientation on a single frontal view of the pelvis, which may be of
      particular interest in understanding the relationship between pelvic orientation
      and hip pathology. LEVEL OF EVIDENCE: IV.

PMID- 24925288
TI  - Lack of harmonization of red blood cell distribution width (RDW). Evaluation of
      four hematological analyzers.
AB  - OBJECTIVES: To assess analytical imprecision and comparability of red blood cell
      distribution width (RDW) on Abbott Sapphire, Mindray BC6800, Siemens Advia 2120
      and Sysmex XE-5000. DESIGN AND METHODS: Within-run imprecision was assessed on
      three pools and comparability using 132 inpatient samples. RESULTS: The
      imprecision of RDW was comprised between 0.3 and 1.2%, but the values exhibited
      broad variation among different analyzers, with bias exceeding the desirable
      quality specifications. CONCLUSIONS: Harmonization of RDW is still an unmet need.

PMID- 24925287
TI  - Effects of eicosapentaenoic acid and docosahexaenoic acid on prostate cancer cell
      migration and invasion induced by tumor-associated macrophages.
AB  - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the major n-3
      polyunsaturated fatty acids (PUFAs) in fish oil that decrease the risk of
      prostate cancer. Tumor-associated macrophages (TAMs) are the main leukocytes of
      intratumoral infiltration, and increased TAMs correlates with poor prostate
      cancer prognosis. However, the mechanism of n-3 PUFAs on prostate cancer cell
      progression induced by TAMs is not well understood. In this study, we
      investigated the effects of EPA and DHA on modulating of migration and invasion
      of prostate cancer cells induced by TAMs-like M2-type macrophages. PC-3 prostate
      cancer cells were pretreated with EPA, DHA, or the peroxisome proliferator
      activated receptor (PPAR)-gamma antagonist, GW9662, before exposure to
      conditioned medium (CM). CM was derived from M2-polarized THP-1 macrophages. The
      migratory and invasive abilities of PC-3 cells were evaluated using a coculture
      system of M2-type macrophages and PC-3 cells. EPA/DHA administration decreased
      migration and invasion of PC-3 cells. The PPAR-gamma DNA-binding activity and
      cytosolic inhibitory factor kappaBalpha (IkappaBalpha) protein expression
      increased while the nuclear factor (NF)-kappaB p65 transcriptional activity and
      nuclear NF-kappaB p65 protein level decreased in PC-3 cells incubated with CM in
      the presence of EPA/DHA. Further, EPA/DHA downregulated mRNA expressions of
      matrix metalloproteinase-9, cyclooxygenase-2, vascular endothelial growth factor,
      and macrophage colony-stimulating factor. Pretreatment with GW9662 abolished the
      favorable effects of EPA/DHA on PC-3 cells. These results indicate that EPA/DHA
      administration reduced migration, invasion and macrophage chemotaxis of PC-3
      cells induced by TAM-like M2-type macrophages, which may partly be explained by
      activation of PPAR-gamma and decreased NF-kappaB p65 transcriptional activity. 

PMID- 24925289
TI  - Measurement of Galectin-3 with the ARCHITECT assay: Clinical validity and cost
      effectiveness in patients with heart failure.
AB  - OBJECTIVES: Galectin-3 (Gal-3) testing is emerging as a valuable tool for the
      prognosis of heart failure (HF). Our objectives were to determine the clinical
      validity and cost-effectiveness of the recently developed ARCHITECT Gal-3
      automated immunoassay. DESIGN AND METHODS: Gal-3 levels were measured in HF
      patients with reduced left ventricular ejection fraction with the ARCHITECT
      i2000SR Gal-3 assay as well as with the reference Gal-3 ELISA assay. The
      relationship between Gal-3 levels determined with the automated assay and HF
      severity as well as its predictive value for long-term cardiovascular death were
      evaluated. The impact of Gal-3 testing on the diagnostic related group (DRG)
      based reimbursement was also estimated. RESULTS: Gal-3 levels measured with the
      ARCHITECT assay were related to the severity of HF based on New York Heart
      Association functional classes (p<0.001) and were also significantly and
      positively correlated to BNP concentrations (r=0.35, p<0.001). Gal-3 values
      higher than 19.2 ng/mL were predictive of long-term cardiovascular death in
      patients with systolic HF and also provided incremental prognostic information to
      BNP testing. In addition, Gal-3 testing was estimated to save DRG in comparison
      to standard of care. CONCLUSIONS: Our results demonstrated the clinical validity
      of the ARCHITECT Gal-3 automated immunoassay for the risk stratification of HF
      patients. The automation of Gal-3 testing was also cost-effective and might help
      to preserve hospital budget.

PMID- 24925290
TI  - Behavioral contrast of a complex operant.
AB  - Two experiments were conducted in which pigeons were trained to perform a complex
      operant consisting of a peck to one key followed by a peck to another key. In the
      first experment this performance was reinforced on a variable-interval schedule
      and the birds were then subjected to a multiple schedule in which the variable
      interval was alternated with extinction. The first two pigeons trained showed
      some deterioration of the cohesiveness of the response sequence. After measures
      were taken to correct this the pigeon gave evidence of behavioral contrast in a
      condition where sessions with discrimination were alternated rapidly with
      sessions with no discrimination (variable-interval only). Another two birds were
      trained on variable-interval followed by discrimination. One of these birds
      showed evidence of contrast but the results of the other were not clear.
      Experiment II was a three phase experiment in which animals were first trained to
      make the complex response. In the second phase they were extinguished by
      providing noncontingent reinforcement in each of two components. In the third
      phase reinforcement was removed from one component, providing for a stimulus
      reinforcer contingency. In the third phase the complex response reappeared
      temporarily. The results of these two studies indicate that a complex response
      may show behavioral contrast and that it may be enhanced by stimulus-reinforcer
      contingencies if it has already been trained. 

PMID- 24925291
TI  - Maternal aggression and intermale social aggression: a behavioral comparison.
AB  - The aggressive behavior of alpha male rats and lactating females were each
      examined toward an intact adult male rat, a castrated adult male rat, an
      anesthetized adult male rat, a nonlactating adult female rat, an adult albino
      guinea pig (male or female), or an albino mouse (male or female). When in their
      living colony, females displayed high levels of aggressiveness toward all
      stimulus objects except a mouse. The aggression toward the intruding males
      occurred whether the female's pups were present or not. Alpha males were
      aggressive toward the same stimuli except an intruding female rat and a mouse.
      When tested in an unfamiliar colony, the males but not the females (with or
      without pups present) were aggressive toward an adult male rat. Half of the
      females but none of the males displayed defensive burying toward an anesthetized
      intruder. It is suggested that the attack on an adult female, the absence of
      attack outside of the resident colony, and the tendency to display defensive
      burying are features of the aggressiveness of lactating females that are
      fundamentally different from the aggressiveness of alpha males. The form of the
      aggression (lateral attack vs. lunge attack) was only quantitatively different in
      males and females. 

PMID- 24925292
TI  - Classical conditioning, signal detection, and evolution.
AB  - Strength of classical conditioning is increased either by increasing
      discriminability of the conditioned stimulus (CS) from the background, or by
      increasing contingency between conditioned and unconditioned stimili (US).
      Classical conditioning can be regarded as a decision process in which the subject
      has to decide whether or not to respond with a conditioned response in the
      presence or absence of the CS. According to modern evolutionary theories, it
      might be assumed that this decision process maximizes the trade-off between cost
      and benefits. By assuming that the decision rule maximizes expected benefit, the
      empirical relationship between contingency and the strength of classical
      conditioning is theoretically derived. In addition, when the decision rule is
      incorporated to a signal detection paradigm, theoretical results describing the
      relationship between CS discriminability and CS - US contingency with the
      strength of classical conditioning are in agreement with experimental data. 

PMID- 24925293
TI  - Behavioural and adrenocortical responses of domestic chicks to systematic
      reductions in group size and to sequential disturbance of companions by the
      experimenter.
AB  - Disruption of an animal's social environment often causes distress and the
      effects of systematic reductions in group size on the behaviour and plasma
      corticosterone concentrations of domestic chicks were assessed in Experiment 1.
      Because this procedure also exposed the chicks to repeated disturbance by the
      experimenter, the behavioural and adrenocortical consequences of sequential
      capture and replacement of social companions were examined in Experiment 2.
      Female White Leghorn chicks were housed in groups of eight and remained
      undisturbed in both experiments until testing began at 14 d of age. Systematic
      reduction of group size was accompanied by both endocrine and behavioural
      modifications in Experiment 1. Thus, plasma corticosterone levels rose, feeding,
      drinking, preening and pecking at the environment gradually ceased whereas
      defaecation, ambulation, jumping and peeping became increasingly prevalent. These
      modifications were generally abrupt rather than progressive. Endocrine changes
      preceded behavioural ones which generally became evident when only two or fewer
      chicks remained. Conversely, the sequential capture and temporary removal of
      chicks from established groups in Experiment 2 elicited no significant effects in
      their uncaptured companions. The results are discussed in terms of social
      disruption, disturbance of companions by the experimenter, social motivation,
      predator evasion, individual recognition and fear. 

PMID- 24925294
TI  - Individual differences in choice of food items by pigeons.
AB  - Pigeons (Columba livia ) select food items idiosyncratically when feeding on
      grains (Brown, 1969; Moon & Zeigler, 1979; Giraldeau & Lefebvre, 1985). In three
      experiments pigeons under various conditions of food restriction were offered
      artificial "grains", pellets of pigeon food that differed only in size, to see
      whether individual differences in preference would still be observed. When 300-mg
      ("large") and 20-mg ("small") pellets were available simultaneously there were
      still wide individual differences in choice, but when encountering the same items
      successively pigeons took nearly all the items offered. 

PMID- 24925295
TI  - Experimental studies on genetically determined predisposition to catatonia in
      rats as a model of schizophrenia.
AB  - To check experimentally the hypothesis of schizophrenia being a manifestation of
      extremely low threshold of hypnotic (catatonic) type of reaction, changes of some
      neurophysiologic and neurochemical systems in rats with a genetic predisposition
      to catalepsy were compared to analogous changes found so far in schizophrenia or
      chronic amphetamine intoxication considered nowadays as the most adequate
      pharmacological model of schizophrenia. It is found that in rats predisposed to
      catalepsy the threshold of audiogenic seizures is elevated; the activity of
      tryptophan hydroxylase in striatum is higher in rats predisposed to catalepsy
      genetically and due to a chronic methylphenidate intoxication as compared to
      control animals; noradrenaline content and noradrenaline/dopamine ratio is lower
      in the diencephalon of rats predisposed to catalepsy than in controls; cataleptic
      rats have a higher content of homovanillic acid in N.accumbens , and a higher
      frequency of inversion of hemispheric asymmetry as estimated by levels of
      dopamine and dioxyphenylacetic acid in N.accumbens and caudate nucleus, than
      normal rats; MAO-B/MAO-A ratio is higher in the brain stem of cataleptic than
      normal rats. The effects of haloperidol and apomorphine on motor activity of
      cataleptic and normal animals point to a higher sensitivity of postsynaptic
      dopamine receptors in the former. Conditioned avoidance reaction is formed
      slower, but preserved longer in rats predisposed to catalepsy. Blood serum of
      wild rats predisposed to akinetic catatonic reactions, unlike the serum of normal
      wild rats, inhibits the electric activity of snail neurons. The above indicated
      changes are analogous to those known to be present in schizophrenia and/or
      chronic intoxication with amphetamine or its pharmacological analogues, which
      witnesses in favour of the proposed hypothesis. 

PMID- 24925300
TI  - Alcohol and Aggression P.F. Brain (ed) Croom Helm, London, 1985 288pp., UK L :
      22,50.

PMID- 24925302
TI  - Low adherence to upfront and extended adjuvant letrozole therapy among early
      breast cancer patients in a clinical practice setting.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence and causes of
      early discontinuation and non-adherence to upfront and extended adjuvant
      letrozole therapy in breast cancer patients. METHODS: Adherence was assessed
      using medical charts and longitudinal pharmacy records of 609 patients who
      initiated adjuvant letrozole between January 2002 and April 2011. A Cox
      proportional hazards regression model was adopted to identify potential
      predictors of non-adherence. RESULTS: The overall adherence rate after 1 year of
      therapy was 79.5%, with cumulative rates declining to 63.7% after 3 years and
      57.1% after 5 years. A significantly lower rate of adherence in the extended
      adjuvant group was observed compared with the upfront adjuvant group (49.0 vs.
      72.5%, p < 0.001). Adverse events (50.4%) were the major cause of early
      discontinuation, with musculoskeletal pain (73.2%) being the single most cited
      reason. Additional factors correlating with non-adherence in the upfront adjuvant
      group included a delay in initiation of adjuvant hormone therapy, breast
      conserving surgery, calcium supplements, bisphosphonate therapy and concomitant
      medication for co-morbidity. CONCLUSIONS: We observed that approximately 57% of
      patients fully adhered to letrozole therapy over a 5-year treatment period, and
      that the adherence to extended letrozole was meaningfully lower than the upfront
      adjuvant letrozole in a clinical practice setting.

PMID- 24925303
TI  - Exploring the effects of galacto-oligosaccharides on the gut microbiota of
      healthy adults receiving amoxicillin treatment.
AB  - In the present double-blind, randomised, parallel intervention study, the effects
      of the intake of galacto-oligosaccharides (GOS) on the gut microbiota of twelve
      healthy adult subjects (aged 18-45 years with a normal BMI (18-25 kg/m2))
      receiving amoxicillin (AMX) treatment were determined. All the subjects were
      treated with AMX (375 mg; three times per d) for 5 d and given either GOS (n 6)
      or placebo (maltodextrin, n 6) (2.5 g; three times per d) during and 7 d after
      AMX treatment. Faecal samples were collected twice before starting the treatment
      and on days 2, 5, 8, 12, 19 and 26. Due to AMX treatment, a decrease in the
      abundance of Bifidobacterium spp., an overgrowth of Enterobacteriaceae, and a
      disruption of the metabolic activity of the microbiota (increase in succinate,
      monosaccharide and oligosaccharide levels in the faecal samples) were observed in
      both groups (P< 0.05). Positive effects of GOS intake were observed on the levels
      of bifidobacteria, although not found to be significant. Data revealed that the
      levels of bifidobacteria were higher upon GOS intake than upon placebo intake,
      especially after AMX treatment. The activity of bifidobacteria and subsequent
      cross-feeding activity of the microbiota upon GOS intake compared with those upon
      placebo intake were reflected by the significant increase in butyrate levels (P<
      0.05) in the faecal samples after AMX treatment. Despite the small number of
      subjects, our findings confirm previous results obtained in vitro, namely that
      GOS intake supports the recovery of the beneficial bifidobacteria and,
      indirectly, the production of butyrate after AMX treatment.

PMID- 24925305
TI  - The anti-diabetic activity of Bifidobacterium lactis HY8101 in vitro and in vivo.
AB  - AIMS: The aim of this study was to evaluate the effects of Bifidobacterium lactis
      HY8101 on insulin resistance induced using tumour necrosis factor-alpha (TNF
      alpha) in rat L6 skeletal muscle cells and on the KK-A(Y) mouse noninsulin
      dependent diabetes mellitus (NIDDM) model. METHODS AND RESULTS: The treatment
      using HY8101 improved the insulin-stimulated glucose uptake and translocation of
      GLUT4 via the insulin signalling pathways AKT and IRS-1(Tyr) in TNF-alpha-treated
      L6 cells. HY8101 increased the mRNA levels of GLUT4 and several insulin
      sensitivity-related genes (PPAR-gamma) in TNF-alpha-treated L6 cells. In KK-A(Y)
      mice, HY8101 decreased fasting insulin and blood glucose and significantly
      improved insulin tolerance. HY8101 improved diabetes-induced plasma total
      cholesterol and triglyceride (TG) levels and increased the muscle glycogen
      content. We observed concurrent transcriptional changes in the skeletal muscle
      tissue and the liver. In the skeletal muscle tissue, the glycogen synthesis
      related gene pp-1 and GLUT4 were up-regulated in mice receiving HY8101 treatment.
      In the liver, the hepatic gluconeogenesis-regulated genes (PCK1 and G6PC) were
      down-regulated in mice receiving HY8101 treatment. CONCLUSIONS: Bifidobacterium
      lactis HY8101 can be used to moderate glucose metabolism, lipid metabolism and
      insulin sensitivity in mice and in cells. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Bifidobacterium lactis HY8101 might have potential as a probiotic candidate for
      alleviating metabolic syndromes such as diabetes.

PMID- 24925304
TI  - Cord blood 25(OH)-vitamin D deficiency and childhood asthma, allergy and eczema:
      the COPSAC2000 birth cohort study.
AB  - BACKGROUND: Epidemiological studies have suggested an association between
      maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy
      in the offspring. However, prospective clinical studies on vitamin D measured in
      cord blood and development of clinical end-points are sparse. OBJECTIVE: To
      investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin
      D) level and investigator-diagnosed asthma- and allergy-related conditions during
      preschool-age. METHODS: Cord blood 25(OH)-Vitamin D level was measured in 257
      children from the Copenhagen Prospective Studies on Asthma in Childhood
      (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS),
      asthma, respiratory infections, allergic rhinitis, and eczema, at age 0-7 yrs
      were diagnosed exclusively by the COPSAC pediatricians strictly adhering to
      predefined algorithms. Objective assessments of lung function and sensitization
      were performed repeatedly from birth. RESULTS: After adjusting for season of
      birth, deficient cord blood 25(OH)-Vitamin D level (<50 nmol/L) was associated
      with a 2.7-fold increased risk of recurrent TROLS (HR = 2.65; 95% CI = 1.02
      6.86), but showed no association with respiratory infections or asthma. We saw no
      association between cord blood 25(OH)-Vitamin D level and lung function,
      sensitization, rhinitis or eczema. The effects were unaffected from adjusting for
      multiple lifestyle factors. CONCLUSION: Cord blood 25(OH)-Vitamin D deficiency
      associated with increased risk of recurrent TROLS till age 7 years. Randomized
      controlled trials of vitamin D supplementation during pregnancy are needed to
      prove causality.

PMID- 24925306
TI  - Making sense of deep sequencing.
AB  - This review, the first of an occasional series, tries to make sense of the
      concepts and uses of deep sequencing of polynucleic acids (DNA and RNA). Deep
      sequencing, synonymous with next-generation sequencing, high-throughput
      sequencing and massively parallel sequencing, includes whole genome sequencing
      but is more often and diversely applied to specific parts of the genome captured
      in different ways, for example the highly expressed portion of the genome known
      as the exome and portions of the genome that are epigenetically marked either by
      DNA methylation, the binding of proteins including histones, or that are in
      different configurations and thus more or less accessible to enzymes that cleave
      DNA. Deep sequencing of RNA (RNASeq) reverse-transcribed to complementary DNA is
      invaluable for measuring RNA expression and detecting changes in RNA structure.
      Important concepts in deep sequencing include the length and depth of sequence
      reads, mapping and assembly of reads, sequencing error, haplotypes, and the
      propensity of deep sequencing, as with other types of 'big data', to generate
      large numbers of errors, requiring monitoring for methodologic biases and
      strategies for replication and validation. Deep sequencing yields a unique
      genetic fingerprint that can be used to identify a person, and a trove of
      predictors of genetic medical diseases. Deep sequencing to identify epigenetic
      events including changes in DNA methylation and RNA expression can reveal the
      history and impact of environmental exposures. Because of the power of sequencing
      to identify and deliver biomedically significant information about a person and
      their blood relatives, it creates ethical dilemmas and practical challenges in
      research and clinical care, for example the decision and procedures to report
      incidental findings that will increasingly and frequently be discovered. 

PMID- 24925307
TI  - Impact of high serum progesterone during the late follicular phase on IVF
      outcome.
AB  - With ovarian stimulation for IVF, serum progesterone concentration may increase
      during the last few days of stimulation. Several factors, mainly the intensity of
      the ovarian response to gonadotrophins, have been identified to explain
      progesterone elevation but many other issues remain uncertain. The aim of this
      narrative, nonsystematic review is to address the nonconsensual issues of the
      reasons and consequences of premature progesterone elevation during ovarian
      stimulation. The determination of the optimal threshold above which progesterone
      elevation may have an impact on IVF outcome is still a matter of debate because
      it is likely related to the patient's profile. Additionally, it is still
      uncertain whether the duration of progesterone elevation negatively affects IVF
      outcome. Recommendations for both prevention and management of progesterone
      elevation are here suggested by a group of experts. Nevertheless, before being
      implemented in clinical practice, they require new assessment through additional
      clinical trials. 

PMID- 24925308
TI  - Comparison of gender-specific human embryo development characteristics by time
      lapse technology.
AB  - Numerous studies indicate that there might be differences in embryo growth
      dynamics between male and female embryos. However, current data in humans are
      scarce and the results are inconclusive or conflicting. This study asks whether
      there exist gender-specific embryo development kinetics or parameters between
      human male and female embryos that can be observed by time-lapse technology.
      Study included data from 139 consecutive cycles (177 embryos transferred, 179
      sacs analysed) with positive pregnancy that resulted in 100% implantation. Single
      or double-embryo transfers were performed. Cases were analysed for parameters
      including cleavage time points and duration in each cleavage from two cells to
      hatching blastocyst stages and time interval between cleavages. Morphokinetic
      parameters of 78 female and 60 male embryos from a total of 119 cycles (139 sacs
      were examined after transfer of 138 embryos) were processed for data analysis
      according to the gender group. A detailed analysis of the data regarding each
      time point or interval between consecutive events according to these groups
      showed them to be similar in cell division kinetics, from the early cleavage
      through their development to blastocyst stage. However, female embryos showed
      earlier cavitation than male embryos, but the results did not reach statistical
      significance. 

PMID- 24925309
TI  - Selection of embryos for transfer in IVF: ranking embryos based on their
      implantation potential using morphological scoring.
AB  - The selection of embryos based on morphology is still the core of daily
      laboratory practice in IVF/intracytoplasmic sperm injection. At present, the
      selection of embryos is primarily based on experience and local protocols. Since
      an evidence-based ranking strategy for embryos on day 3 is currently lacking,
      this work constructed a multivariable prediction model to rank embryos according
      to their implantation potential. A total of 6021 fresh embryo transfers between
      January 2004 and July 2009 were included, eight potential predictive factors were
      evaluated and a prediction model was developed using multivariable logistic
      regression. The model was externally validated with data from couples treated
      between August 2009 and September 2011 in the same clinic. Five factors were
      included in the final prediction model: early cleavage, number of blastomeres on
      days 2 and 3 and morphological score and presence of morula on day 3. With
      validation, the model showed moderate discriminative capacity (c-statistic 0.70)
      and calibrated well and was able to distinguish embryos with high ongoing
      implantation potential from embryos with moderate or low ongoing implantation
      potential. The model can be used by embryologists as an objective tool to rank
      embryos according to implantation potential, thereby aiding the selection of
      embryos for transfer. 

PMID- 24925310
TI  - Abdominal obesity and its association with health-related quality of life in
      adults: a population-based study in five Chinese cities.
AB  - BACKGROUND: This study aimed to investigate the prevalence of abdominal obesity
      and its association with the health-related quality of life (HRQOL) in a randomly
      selected Chinese sample. METHODS: A population-based sample of 3,600 residents
      aged 18-80 years was selected randomly from 5 Chinese cities. Demographic
      information, and waist and hip circumference measurements were obtained. The
      Mandarin version of the Short Form 36 Health Survey questionnaire (SF-36) was
      used to assess the HRQOL. Waist circumference (WC) and waist-to-hip ratio (WHR)
      were used as measures of abdominal obesity, and the prevalence of abdominal
      obesity and its association with HRQOL were analysed. RESULTS: Among the 3,184
      participants included in the analysis, the prevalence of abdominal obesity was
      about 45% in both women and men as evaluated by WC, and about 40% in women and
      33% in men as evaluated by WHR. The prevalence varied by city, region, age,
      marital status, education level, family income, smoking, and the presence of
      chronic diseases. Both WC and WHR increased with age, and men had larger WC and
      WHR than women in most age groups. In women, abdominal obesity, as determined by
      both WC and WHR, was associated with meaningful impairments in 4 physical health
      scales and 2 mental health scales. In men, abdominal obesity, as determined by
      WC, was associated with 1 physical health scale and 1 mental health scale, and it
      was associated with 2 physical health scales based on WHR. CONCLUSIONS: Physical
      health, but not mental health, was more vulnerable to impairment with abdominal
      obesity, and the impairments varied between genders. Public health agencies
      should emphasize that abdominal obesity impairs physical health.

PMID- 24925312
TI  - Primary tracheoesophageal puncture with supraclavicular artery island flap after
      total laryngectomy or laryngopharyngectomy.
AB  - The supraclavicular artery island flap (SCAIF) is increasingly employed for
      laryngectomy reconstruction with excellent success. Although tracheoesophageal
      puncture (TEP) with intraoperative prosthesis placement is also positively
      reported, this is not described in patients following SCAIF. We review our
      experience with primary TEP with prosthesis placement and voice outcomes in
      patients after SCAIF reconstruction. Seven patients underwent SCAIF with primary
      TEP after laryngectomy from 2011 to 2013. Five underwent total laryngectomy (TL)
      and 2 underwent TL with partial pharyngectomy. All patients had 16 French
      Indwelling Blom-Singer prostheses placed intraoperatively without complications.
      Six patients achieved tracheoesophageal voice (median time = 1.5 months). Two
      patients required cricopharyngeal segment Botox injections. One patient remained
      aphonic. One patient developed prosthesis leakage addressed with prosthesis
      replacement. Our preliminary data demonstrate that similar to free tissue
      transfer reconstruction, primary TEP with intraoperative placement of the voice
      prosthesis at the time of SCAIF reconstruction is safe and effective.

PMID- 24925311
TI  - The "new" head and neck cancer patient-young, nonsmoker, nondrinker, and HPV
      positive: evaluation.
AB  - OBJECTIVE: The near epidemic rise of the incidence of human papillomavirus (HPV)
      related oropharyngeal squamous cell carcinomas (OPSCC) presents the practitioner
      with a "new" head and neck cancer patient, vastly different from those with the
      traditional risk factors who formed the basis of most practitioners' training
      experience. Accordingly, a thorough and disease-specific evaluation process is
      necessitated. This article will review the evaluation of the HPV-related cancer
      patient, including a review of the HPV-positive oropharyngeal cancer epidemic
      from the surgeon's perspective, evaluation of the primary lesion, evaluation of
      the neck mass, and role of imaging, to provide a framework for addressing the
      challenging questions patients may ask. DATA SOURCES: Available peer-reviewed
      literature and practice guidelines. REVIEW METHODS: Assessment of selected
      specific topics by authors solicited from the Head and Neck Surgery and Oncology
      Committee of the American Academy of Otolaryngology-Head and Neck Surgery
      Foundation and the American Head and Neck Society. CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: The dramatic rise in OPSSC related to HPV is characterized by a
      "new" cancer patient who is younger and lacks traditional risk factors. Today's
      caregiver must be prepared to appropriately evaluate, counsel, and treat these
      patients with HPV-positive disease with the expectation that traditional
      treatment algorithms will evolve to maintain or improve current excellent cure
      rates while lessening treatment related side effects.

PMID- 24925313
TI  - Cystatin C, a novel indicator of renal function, reflects severity of cerebral
      microbleeds.
AB  - BACKGROUND: Chronic renal insufficiency, diagnosed using creatinine based
      estimated glomerular filtration rate (GFR) or microalbumiuria, has been
      associated with the presence of cerebral microbleeds (CMBs). Cystatin C has been
      shown to be a more sensitive renal indicator than conventional renal markers.
      Under the assumption that similar pathologic mechanisms of the small vessel exist
      in the brain and kidney, we hypothesized that the levels of cystatin C may
      delineate the relationship between CMBs and renal insufficiency by detecting
      subclinical kidney dysfunction, which may be underestimated by other indicators,
      and thus reflect the severity of CMBs more accurately. METHODS: Data was
      prospectively collected for 683 patients with ischemic stroke. The severity of
      CMBs was categorized by the number of lesions. Patients were divided into
      quartiles of cystatin C, estimated GFR and microalbumin/creatinine ratios.
      Ordinal logistic regression analysis was used to examine the association of each
      renal indicator with CMBs. RESULTS: In models including both quartiles of
      cystatin C and estimated GFR, only cystatin C quartiles were significant (the
      highest vs. the lowest, adjusted OR, 1.88; 95% CI 1.05-3.38; p = 0.03) in
      contrast to estimated GFR (the highest vs. the lowest, adjusted OR, 1.28; 95% CI
      0.38-4.36; p = 0.70). A model including both quartiles of cystatin C and
      microalbumin/creatinine ratio also showed that only cystatin C quartiles was
      associated with CMBs (the highest vs. the lowest, adjusted OR, 2.06; 95% CI 1.07
      3.94; p = 0.03). These associations were also observed in the logistic models
      using log transformed-cystatin C, albumin/creatinine ratio and estimated GFR as
      continuous variables. Cystatin C was a significant indicator of deep or
      infratenorial CMBs, but not strictly lobar CMBs. In addition, cystatin C showed
      the greatest significance in c-statistics for the presence of CMBs (AUC = 0.73 +/
      0.03; 95% CI 0.66-0.76; p = 0.02). CONCLUSION: Cystatin C may be the most
      sensitive indicator of CMB severity among the renal disease markers.

PMID- 24925314
TI  - Reversing the pump dependence of a laser at an exceptional point.
AB  - When two resonant modes in a system with gain or loss coalesce in both their
      resonance position and their width, a so-called exceptional point occurs, which
      acts as a source of non-trivial physics in a diverse range of systems. Lasers
      provide a natural setting to study such non-Hermitian degeneracies, as they
      feature resonant modes and a gain material as their basic constituents. Here we
      show that exceptional points can be conveniently induced in a photonic molecule
      laser by a suitable variation of the applied pump. Using a pair of coupled
      microdisk quantum cascade lasers, we demonstrate that in the vicinity of these
      exceptional points the coupled laser shows a characteristic reversal of its pump
      dependence, including a strongly decreasing intensity of the emitted laser light
      for increasing pump power. 

PMID- 24925315
TI  - Gaucher disease due to saposin C deficiency is an inherited lysosomal disease
      caused by rapidly degraded mutant proteins.
AB  - Saposin (Sap) C is an essential cofactor for the lysosomal degradation of
      glucosylceramide (GC) by glucosylceramidase (GCase) and its functional impairment
      underlies a rare variant form of Gaucher disease (GD). Sap C promotes
      rearrangement of lipid organization in lysosomal membranes favoring substrate
      accessibility to GCase. It is characterized by six invariantly conserved cysteine
      residues involved in three intramolecular disulfide bonds, which make the protein
      remarkably stable to acid environment and degradation. Five different mutations
      (i.e. p.C315S, p.342_348FDKMCSKdel, p.L349P, p.C382G and p.C382F) have been
      identified to underlie Sap C deficiency. The molecular mechanism by which these
      mutations affect Sap C function, however, has not been delineated in detail.
      Here, we characterized biochemically and functionally four of these gene lesions.
      We show that all Sap C mutants are efficiently produced, and exhibit lipid
      binding properties, modulatory behavior on GCase activity and subcellular
      localization comparable with those of the wild-type protein. We then delineated
      the structural rearrangement of these mutants, documenting that most proteins
      assume diverse aberrant disulfide bridge arrangements, which result in a
      substantial diminished half-life, and rapid degradation via autophagy. These
      findings further document the paramount importance of disulfide bridges in the
      stability of Sap C and provide evidence that accelerated degradation of the Sap C
      mutants is the underlying pathogenetic mechanism of Sap C deficiency. 

PMID- 24925316
TI  - Tuning intracellular homeostasis of human uroporphyrinogen III synthase by enzyme
      engineering at a single hotspot of congenital erythropoietic porphyria.
AB  - Congenital erythropoietic porphyria (CEP) results from a deficiency in
      uroporphyrinogen III synthase enzyme (UROIIIS) activity that ultimately stems
      from deleterious mutations in the uroS gene. C73 is a hotspot for these mutations
      and a C73R substitution, which drastically reduces the enzyme activity and
      stability, is found in almost one-third of all reported CEP cases. Here, we have
      studied the structural basis, by which mutations in this hotspot lead to UROIIIS
      destabilization. First, a strong interdependency is observed between the volume
      of the side chain at position 73 and the folded protein. Moreover, there is a
      correlation between the in vitro half-life of the mutated proteins and their
      expression levels in eukaryotic cell lines. Molecular modelling was used to
      rationalize the results, showing that the mutation site is coupled to the hinge
      region separating the two domains. Namely, mutations at position 73 modulate the
      inter-domain closure and ultimately affect protein stability. By incorporating
      residues capable of interacting with R73 to stabilize the hinge region, catalytic
      activity was fully restored and a moderate increase in the kinetic stability of
      the enzyme was observed. These results provide an unprecedented rationale for a
      destabilizing missense mutation and pave the way for the effective design of
      molecular chaperones as a therapy against CEP. 

PMID- 24925317
TI  - TNNI3K mutation in familial syndrome of conduction system disease, atrial
      tachyarrhythmia and dilated cardiomyopathy.
AB  - Locus mapping has uncovered diverse etiologies for familial atrial fibrillation
      (AF), dilated cardiomyopathy (DCM), and mixed cardiac phenotype syndromes, yet
      the molecular basis for these disorders remains idiopathic in most cases. Whole
      exome sequencing (WES) provides a powerful new tool for familial disease gene
      discovery. Here, synergistic application of these genomic strategies identified
      the pathogenic mutation in a familial syndrome of atrial tachyarrhythmia,
      conduction system disease (CSD), and DCM vulnerability. Seven members of a three
      generation family exhibited the variably expressed phenotype, three of whom
      manifested CSD and clinically significant arrhythmia in childhood. Genome-wide
      linkage analysis mapped two equally plausible loci to chromosomes 1p3 and 13q12.
      Variants from WES of two affected cousins were filtered for rare, predicted
      deleterious, positional variants, revealing an unreported heterozygous missense
      mutation disrupting the highly conserved kinase domain in TNNI3K. The G526D
      substitution in troponin I interacting kinase, with the most deleterious SIFT and
      Polyphen2 scores possible, resulted in abnormal peptide aggregation in vitro and
      in silico docking models predicted altered yet energetically favorable wild-type
      mutant dimerization. Ventricular tissue from a mutation carrier displayed
      histopathological hallmarks of DCM and reduced TNNI3K protein staining with
      unique amorphous nuclear and sarcoplasmic inclusions. In conclusion, mutation of
      TNNI3K, encoding a heart-specific kinase previously shown to modulate cardiac
      conduction and myocardial function in mice, underlies a familial syndrome of
      electrical and myopathic heart disease. The identified substitution causes a
      TNNI3K aggregation defect and protein deficiency, implicating a dominant-negative
      loss of function disease mechanism. 

PMID- 24925318
TI  - POMK mutations disrupt muscle development leading to a spectrum of neuromuscular
      presentations.
AB  - Dystroglycan is a transmembrane glycoprotein whose interactions with the
      extracellular matrix (ECM) are necessary for normal muscle and brain development,
      and disruptions of its function lead to dystroglycanopathies, a group of
      congenital muscular dystrophies showing extreme genetic and clinical
      heterogeneity. Specific glycans bound to the extracellular portion of
      dystroglycan, alpha-dystroglycan, mediate ECM interactions and most known
      dystroglycanopathy genes encode glycosyltransferases involved in glycan
      synthesis. POMK, which was found mutated in two dystroglycanopathy cases, is
      instead involved in a glycan phosphorylation reaction critical for ECM binding,
      but little is known about the clinical presentation of POMK mutations or of the
      function of this protein in the muscle. Here, we describe two families carrying
      different truncating alleles, both removing the kinase domain in POMK, with
      different clinical manifestations ranging from Walker-Warburg syndrome, the most
      severe form of dystroglycanopathy, to limb-girdle muscular dystrophy with
      cognitive defects. We explored POMK expression in fetal and adult human muscle
      and identified widespread expression primarily during fetal development in
      myocytes and interstitial cells suggesting a role for this protein during early
      muscle differentiation. Analysis of loss of function in the zebrafish embryo and
      larva showed that pomk function is necessary for normal muscle development,
      leading to locomotor dysfuction in the embryo and signs of muscular dystrophy in
      the larva. In summary, we defined diverse clinical presentations following POMK
      mutations and showed that this gene is necessary for early muscle development. 

PMID- 24925319
TI  - Single-molecule tracking in live cells reveals distinct target-search strategies
      of transcription factors in the nucleus.
AB  - Gene regulation relies on transcription factors (TFs) exploring the nucleus
      searching their targets. So far, most studies have focused on how fast TFs
      diffuse, underestimating the role of nuclear architecture. We implemented a
      single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is
      a global explorer of the nucleus. In contrast, the positive transcription
      elongation factor P-TEFb is a local explorer that oversamples its environment.
      Consequently, each c-Myc molecule is equally available for all nuclear sites
      while P-TEFb reaches its targets in a position-dependent manner. Our observations
      are consistent with a model in which the exploration geometry of TFs is
      restrained by their interactions with nuclear structures and not by exclusion.
      The geometry-controlled kinetics of TFs target-search illustrates the influence
      of nuclear architecture on gene regulation, and has strong implications on how
      proteins react in the nucleus and how their function can be regulated in space
      and time. 

PMID- 24925321
TI  - Development of etofenamate-loaded semisolid sln dispersions and evaluation of
      anti-inflammatory activity for topical application.
AB  - Dermal application of various active substances is widely preferred for topical
      or systemic delivery. SLNs consist of biocompatible and non-toxic lipids and have
      a great potential for topical application in drugs. In this study, semisolid SLN
      formulations were successfully prepared by a novel one-step production method as
      a topical delivery system of etofenamate, an anti-inflammatory drug. Compritol
      888 ATO and Precirol ATO 5 were chosen as lipid materials for the fabrication of
      the formulations. In-vitro evaluation of the formulations was performed in terms
      of encapsulation efficiency, particle size, surface charge, thermal behavior,
      rheological characteristics, in vitro drug release profile, kinetics, mechanisms,
      stability, and anti-inflammatory activity. The colloidal size and spherical shape
      of the particles were proved. According to the results of the rheological
      analysis, it was demonstrated that the semisolid SLN formulations have a gel-like
      structure. Stability studies showed that semisolid SLNs were stable at 4 degrees
      C for a six month period. Zero order release was obtained with Precirol ATO 5,
      while Compritol 888 ATO followed the square root of time (Higuchi's pattern)
      dependent release. Semisolid SLNs showed higher inhibitory activity of COX in
      comparison with pure etofenamate. In conclusion, etofenamate-loaded semisolid SLN
      formulations can be successfully prepared in a novel one-step production method
      and useful for topical application. 

PMID- 24925320
TI  - Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal
      reception.
AB  - Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded
      morphogenic signal is interpreted accordingly in neighboring cells to specify
      tissue patterns during development. Here, we report endocytic sorting signals for
      the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to
      degradation in lysosomes. These signals are recognized by two HECT-domain
      ubiquitin E3 ligases, Smurf1 and Smurf2, which are induced by Shh and become
      enriched in Caveolin-1 lipid rafts in association with Ptch1. Smurf-mediated
      endocytic turnover of Ptch1 is essential for its clearance from the primary
      cilium and pathway activation. Removal of both Smurfs completely abolishes the
      ability of Shh to sustain the proliferation of postnatal granule cell precursors
      in the cerebellum. These findings reveal a novel step in the Shh pathway
      activation as part of the Ptch1 negative feedback loop that precisely controls
      the signaling output in response to Shh gradient signal. 

PMID- 24925322
TI  - Incomplete sequence homogenization in 45S rDNA multigene families: intermixed IGS
      heterogeneity within the single NOR locus of the polyploid species Medicago
      arborea (Fabaceae).
AB  - BACKGROUND AND AIMS: Ribosomal sequences have become the classical example of the
      genomic homogenization of nuclear multigene families. Despite theoretical
      advantages and modelling predictions that support concerted evolution of the 45S
      rDNA, several reports have found intragenomic polymorphisms. However, the origins
      and causes of these rDNA polymorphisms are difficult to assess because seed
      plants show a wide range of 45S rDNA loci number variation, especially in
      polyploids. Medicago arborea is a tetraploid species that has a single 45S rDNA
      locus. This feature makes this species a suitable case study to assess the fate
      of ribosomal IGS homogenization in polyploid species showing nucleolus organizer
      region (NOR) reduction. METHODS: The intergenic spacer (IGS) region was amplified
      by long PCR and the fragments were cloned and sequenced by a primer-walking
      strategy. The physical mapping of the whole and partial IGS variants was assessed
      by fluorescent in situ hybridization (FISH) and fibre-FISH methods on mitotic
      chromosomes and extended DNA fibres, respectively. KEY RESULTS: Two IGS fragments
      of 4.8 and 3.5 kb were obtained showing structural features of functional
      sequences. The shorter variant appears to be a truncated copy of the 4.8 kb
      fragment that lacks the duplication of the transcription initiation site region
      and the entire D region. The physical localization of the two IGS variants on
      metaphase chromosomes and extended DNA fibres using FISH corroborated their joint
      presence within the same locus. In addition, no spatial structure of the two
      variants was detected within the NOR. CONCLUSIONS: The results suggest that full
      sequence homogenization is not operating within the NOR locus of M. arborea. The
      structure of the NOR locus reported here departs from the models of IGS
      heterogeneity present in plants and caution against assuming the widespread
      belief that intragenomic ribosomal heterogeneity is mainly due to sequence
      variation between paralogous loci.

PMID- 24925323
TI  - A modelling framework to simulate foliar fungal epidemics using functional
      structural plant models.
AB  - BACKGROUND AND AIMS: Sustainable agriculture requires the identification of new,
      environmentally responsible strategies of crop protection. Modelling of
      pathosystems can allow a better understanding of the major interactions inside
      these dynamic systems and may lead to innovative protection strategies. In
      particular, functional-structural plant models (FSPMs) have been identified as a
      means to optimize the use of architecture-related traits. A current limitation
      lies in the inherent complexity of this type of modelling, and thus the purpose
      of this paper is to provide a framework to both extend and simplify the modelling
      of pathosystems using FSPMs. METHODS: Different entities and interactions
      occurring in pathosystems were formalized in a conceptual model. A framework
      based on these concepts was then implemented within the open-source OpenAlea
      modelling platform, using the platform's general strategy of modelling plant
      environment interactions and extending it to handle plant interactions with
      pathogens. New developments include a generic data structure for representing
      lesions and dispersal units, and a series of generic protocols to communicate
      with objects representing the canopy and its microenvironment in the OpenAlea
      platform. Another development is the addition of a library of elementary models
      involved in pathosystem modelling. Several plant and physical models are already
      available in OpenAlea and can be combined in models of pathosystems using this
      framework approach. KEY RESULTS: Two contrasting pathosystems are implemented
      using the framework and illustrate its generic utility. Simulations demonstrate
      the framework's ability to simulate multiscaled interactions within pathosystems,
      and also show that models are modular components within the framework and can be
      extended. This is illustrated by testing the impact of canopy architectural
      traits on fungal dispersal. CONCLUSIONS: This study provides a framework for
      modelling a large number of pathosystems using FSPMs. This structure can
      accommodate both previously developed models for individual aspects of
      pathosystems and new ones. Complex models are deconstructed into separate
      'knowledge sources' originating from different specialist areas of expertise and
      these can be shared and reassembled into multidisciplinary models. The framework
      thus provides a beneficial tool for a potential diverse and dynamic research
      community.

PMID- 24925324
TI  - Serological and molecular prevalence of swine influenza virus on farms in
      northwestern Mexico.
AB  - The aim of this study was to provide an overview of the epidemiological status of
      swine influenza viruses in pigs from northwestern Mexico in 2008-2009. A
      serological and molecular survey was conducted in 150 pigs from 15 commercial
      farms in Sonora, Mexico (northwestern region of Mexico). The serological data
      showed that 55% of the sera were positive for the H1N1 subtype, 59% for the H3N2
      subtype, and 38% for both subtypes. Overall, 16.6% (25/150) of the samples were
      positive for type A influenza by qRT-PCR. The phylogenetic analysis of the H1
      viruses circulating in northwestern Mexico were grouped into cluster alpha, from
      five other clusters previously described. The influenza virus H1 circulating in
      northwestern Mexico showed 97-100% identity at the nucleotide level among them,
      89% identity with other North American strains, 88% with strains from central
      Mexico, and 85% with the pandemic A/H1N1p2009 virus. Meanwhile, a closer
      relationship with some influenza viruses from North America (97% nucleotide
      identity) was found for H3 subtype. In conclusion, our results demonstrated a
      high circulation of strains similar to those observed in the North American
      linage among commercial farms in northwestern Mexico, involving of a different
      lineage virus different to the influenza pandemic of 2009. 

PMID- 24925325
TI  - A foregone conclusion?: risk stratification in pacemaker-associated endocarditis.

PMID- 24925326
TI  - Prognostic value of coronary CTA in coronary bypass patients: a long-term follow
      up study.
AB  - OBJECTIVES: The goal of this study was to determine the long-term prognostic
      value of coronary computed tomography angiography (CTA) in a large coronary
      artery bypass graft (CABG) population. BACKGROUND: Coronary CTA has shown
      prognostic utility in patients without previous revascularization. However,
      prognostication with coronary CTA in CABG patients has not been fully assessed.
      METHODS: Between March 2005 and April 2009, 887 consecutive CABG patients (mean
      age 66.8 +/- 8.4 years) were considered for the inclusion in the study. Patients
      were classified by the number of unprotected coronary territories (UCTs) and a
      summary of native vessel disease and graft patency: the coronary artery
      protection score (CAPS). A primary endpoint (cardiovascular [CV] death, nonfatal
      myocardial infarction [MI]) and a secondary combined adverse events endpoint (CV
      death, MI, unstable angina, and late revascularizations) were recorded. RESULTS:
      Among the 887 evaluated, 166 did not meet the inclusion criteria. The final study
      population consisted of 721 subjects. Ten patients were excluded for unevaluable
      coronary CTA images. Of the remaining 711 patients, follow-up (mean 73.5 +/- 14
      months) was obtained in 698. Three hundred forty-seven events were recorded. By
      univariable analysis, the strongest coronary CTA predictors of events were UCT 2
      and 3 (hazard ratio [HR] for CV death/MI: 7.5 and 10.19, p < 0.0001 and p <
      0.0003, respectively) and CAPS 4 (HR for CV death/MI: 24.1, p < 0.0001). A high
      number of UCTs was also a strong multivariable independent predictor of CV
      death/MI (HR: 7.78 and 10.18 for UCT 2 and 3, p < 0.0001 and p < 0.0007,
      respectively). Cumulative survival rates for CV death/MI and composite adverse CV
      events were 86% and 73% with UCT 0, 84% and 49% with UCT 1, 53% and 3% with UCT
      2, and 29% and 0% with UCT 3, respectively. CONCLUSIONS: Coronary CTA appears to
      be a promising tool for long-term risk stratification of CABG patients. The UCT
      score has significant prognostic value to predict CV deaths/MI.

PMID- 24925327
TI  - Protected coronary arteries: do open grafts pave the way to survival?

PMID- 24925329
TI  - Multimodality imaging of aortitis.
AB  - Multimodality imaging of aortitis is useful for identification of acute and
      chronic mural changes due to inflammation, edema, and fibrosis, as well as
      characterization of structural luminal changes including aneurysm and stenosis or
      occlusion. Identification of related complications such as dissection, hematoma,
      ulceration, rupture, and thrombosis is also important. Imaging is often vital for
      obtaining specific diagnoses (i.e., Takayasu arteritis) or is used adjunctively
      in atypical cases (i.e., giant cell arteritis). The extent of disease is
      established at baseline, with associated therapeutic and prognostic implications.
      Imaging of aortitis may be useful for screening, routine follow up, and
      evaluation of treatment response in certain clinical settings. Localization of
      disease activity and structural abnormality is useful for guiding biopsy or
      surgical revascularization or repair. In this review, we discuss the available
      imaging modalities for diagnosis and management of the spectrum of aortitis
      disorders that cardiovascular physicians should be familiar with for facilitating
      optimal patient care.

PMID- 24925328
TI  - Comparative definitions for moderate-severe ischemia in stress nuclear,
      echocardiography, and magnetic resonance imaging.
AB  - The lack of standardized reporting of the magnitude of ischemia on noninvasive
      imaging contributes to variability in translating the severity of ischemia across
      stress imaging modalities. We identified the risk of coronary artery disease
      (CAD) death or myocardial infarction (MI) associated with >=10% ischemic
      myocardium on stress nuclear imaging as the risk threshold for stress
      echocardiography and cardiac magnetic resonance. A narrative review revealed that
      >=10% ischemic myocardium on stress nuclear imaging was associated with a median
      rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For
      stress echocardiography, >=3 newly dysfunctional segments portend a median rate
      of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although
      imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance
      may be indicated by >=4 of 32 stress perfusion defects or >=3 dobutamine-induced
      dysfunctional segments. Risk-based thresholds can define equivalent amounts of
      ischemia across the stress imaging modalities, which will help to translate a
      common understanding of patient risk on which to guide subsequent management
      decisions.

PMID- 24925330
TI  - Clinical pacing post-conditioning during revascularization after AMI.
AB  - Intermittent dyssynchrony, induced by ventricular pacing, during early
      reperfusion reduces infarct size in pre-clinical studies. We evaluated
      cardioprotection by pacing post-conditioning (PPC) in ST-segment elevation
      myocardial infarction in a randomized, controlled, single-center, single-blinded,
      first-in-man study. Patients with first ST-segment elevation myocardial
      infarction received either PPC plus percutaneous coronary intervention (PCI) (n =
      30) or PCI (n = 30). PPC consisted of 10 episodes of 30-s right ventricular
      pacing. Infarct size was measured as the area under the curve of creatine kinase
      (CK) (primary endpoint) and by contrast-enhanced cardiac magnetic resonance. The
      CK area under the curve was not significantly different between study groups.
      Adjusted contrast-enhanced cardiac magnetic resonance data showed ~25% smaller
      infarct size in PPC + PCI than in PCI patients after 4 days (p = 0.01), 4 months
      (p = 0.02), and 1 year of PCI (p = 0.08). In PPC + PCI, (uncomplicated)
      ventricular fibrillation (n = 3) and paroxysmal atrial fibrillation (n = 4) were
      observed as opposed to 1 and 0 cases in PCI, respectively. We conclude PPC is
      feasible and may induce cardioprotection during PCI treatment of ST-segment
      elevation myocardial infarction, but technical improvements are needed to improve
      safety. (PROTECT: Pacing to Protect Heart for Damage From Blocked Heart Vessel
      and From Re-opening Blocked Vessel[s]; NCT00409604).

PMID- 24925331
TI  - Emerging role of MDCT in planning complex structural transcatheter intervention.

PMID- 24925332
TI  - Is low CACs really different from zero...: a report from the CACTI study.

PMID- 24925333
TI  - Mechanism of aortic valve opening: beyond the pressure gradient.

PMID- 24925334
TI  - Assessment of lung ultrasound artifacts (B-lines): incremental contribution to
      echocardiography in heart failure?

PMID- 24925335
TI  - B-lines: to count or not to count?

PMID- 24925336
TI  - Reply: B-lines: a nonspecific but highly informative sign of pulmonary
      congestion.

PMID- 24925337
TI  - The last cover.

PMID- 24925338
TI  - Learning from our European imaging colleagues.

PMID- 24925339
TI  - The contribution of dorsolateral prefrontal cortex and temporoparietal areas in
      processing instrumental versus functional semantic violations in action
      representation.
AB  - In the present study, we explored the contribution of different cortical areas in
      processing different semantic violations in action representation--that is,
      instrumental or functional violations. The cortical contribution in object
      related action comprehension was verified by measuring changes in event-related
      potential (N400 effect), error rates (ERs), and response times (RTs), by applying
      an inhibitory transcranial direct current stimulation (tDCS) on the dorsolateral
      prefrontal cortex (DLPFC). Thirty-three subjects performed the detection task
      (action frames ending with a congruous vs. incongruous action). The tDCS effect
      was analyzed by comparing the N400, ERs, and RTs before and after stimulation. A
      significant reduction of the N400 and increased RTs were observed for incongruous
      stimuli in the case of inhibitory stimulation of the DLPFC. These results
      highlighted that DLPFC inhibition may limit the ability to analyze a semantically
      incongruous action, with a reduced N400 ERP effect and increased "cognitive
      costs" (higher RTs). Moreover, functional violation showed also the contribution
      of the temporoparietal areas to modulate the N400 amplitude. Therefore the
      existence of different cortical generators was supposed for the instrumental
      (more frontal) and the functional (more frontal and temporoparietal) semantic
      anomaly processing.

PMID- 24925340
TI  - Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and
      cross the gastric mucus barrier.
AB  - Development of effective non-viral vectors is of crucial importance in the
      implementation of RNA interference in clinical routine. The localized delivery of
      siRNAs to the gastrointestinal mucosa is highly desired but faces specific
      problems such as the stability in gastric acidity conditions and the presence of
      the mucus barrier. CDX2 is a transcription factor critical for intestinal
      differentiation being involved in the initiation and maintenance of
      gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal
      metaplasia which is a precursor lesion of gastric cancer. Its expression is also
      altered in colorectal cancer, where it may constitute a lineage-survival
      oncogene. Our main objective was to develop a nanoparticle-delivery system of
      siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was
      assessed in gastric carcinoma cell lines and nanoparticles behaviour in
      gastrointestinal mucus was tested in mouse explants. We show that imidazole
      modified chitosan and trimethylchitosan/siRNA nanoparticles are able to
      downregulate CDX2 expression and overpass the gastric mucus layer but not colonic
      mucus. This system might constitute a potential therapeutic approach to treat
      CDX2-dependent gastric lesions. 

PMID- 24925341
TI  - The potential roles of cell surface pHs in bioactive peptide activation.
AB  - Glycolytic metabolism of cells produces protons that are removed from the cytosol
      by transport proteins to create a pH difference between the adjacent bulk
      solution and the cell membrane surface. Therefore, tissue cells have distinct
      surface pHs because of varied glycocalyx and proton production capability. In
      this study, we proved the role of cell surface pH in peptide-cell interaction and
      peptide activation using lytic peptides with pH-dependent activity as probes.
      Properly, selected peptides could sense the specific pH zones on cells and thus
      demonstrated varied activity to tissue cells with different surface pHs. For a
      specific cell, the activity of pH-sensitive peptides changed accordingly as the
      cell surface pH was tuned up or down by proton channel regulators. Mechanistic
      studies revealed that cell surface pH directly affected peptide insertion into
      membranes by altering the secondary structure and aggregation status of membrane
      bound pH-sensitive peptides. A pH-sensitive lytic peptide-designed based on the
      cell surface pH difference between a normal-cancer cell pair showed good
      selectivity to cancer cells. Therefore, cell surface pHs may present new
      opportunities to design therapeutic peptides with high cell specificity and
      selectivity. 

PMID- 24925342
TI  - Phylogenetic analysis of human immunodeficiency virus type 2 isolated from Cuban
      individuals.
AB  - The presence of infection by human immunodeficiency virus type 2 (HIV-2) in Cuba
      has been previously documented. However, genetic information on the strains that
      circulate in the Cuban people is still unknown. The present work constitutes the
      first study concerning the phylogenetic relationship of HIV-2 Cuban isolates
      conducted on 13 Cuban patients who were diagnosed with HIV-2. The env sequences
      were analyzed for the construction of a phylogenetic tree with reference
      sequences of HIV-2. Phylogenetic analysis of the env gene showed that all the
      Cuban sequences clustered in group A of HIV-2. The analysis indicated several
      independent introductions of HIV-2 into Cuba. The results of the study will
      reinforce the program on the epidemiological surveillance of the infection in
      Cuba and make possible further molecular evolutionary studies.

PMID- 24925343
TI  - Voltage-gated K(+) channels contributing to temporal precision at the inner hair
      cell-auditory afferent nerve fiber synapses in the mammalian cochlea.
AB  - To perform auditory tasks such as sound localization in the space, auditory
      neurons in the brain must distinguish sub-millisecond temporal differences in
      signals from two ears. Such high temporal resolution is possible when each neuron
      in the ascending auditory pathway fires brief action potential at very accurate
      timing. Various pre- and postsynaptic machineries ensuring such high temporal
      precision of auditory synaptic transmission have been identified. Of particular,
      in this review, the role of K(+) channels in shortening the duration of synaptic
      potentials will be discussed. First, the contribution of K(+) channels to AP
      firing of general auditory neurons will be discussed. Then, the focus will be
      moved to the inner hair cell (IHC)-auditory afferent nerve fiber (ANF) synapses,
      the first synapses of ascending auditory pathway. Molecular and
      immunohistological techniques have revealed various K(+) channels in the cell
      bodies and their processes of ANFs. Since the development of patch-clamp
      recordings from the ANF dendrites in 2002, it became possible to monitor the IHC
      ANF synaptic transmission in greater detail. As revealed in brain auditory
      synapses, several different K(+) channels appear to participate in reducing the
      duration of synaptic potentials at the IHC-ANF synapses. In addition, K(+)
      channels at the ANF dendrites might act as potential targets of efferent feedback
      from the brain. The hypothesis is that, upon loud sound exposure, efferent
      neurotransmitters released onto the ANF dendrites activate certain K(+) channels
      and prevent excitotoxicity of ANFs. Therefore, K(+) channels of the ANF dendrites
      might provide potential sites of pharmacological actions to prevent noise-induced
      hearing loss. 

PMID- 24925344
TI  - Discovery and synthesis of novel allylthioaralkylthiopyridazines: their
      antiproliferative activity against MCF-7 and Hep3B cells.
AB  - A new series of 6-allylthio-3-aralkylthio-4,5-dimethylpyridazines 5a-5k and 1
      allylthio-4-alkylthio-5,6,7,8-tetrahydrophthalazine 6a-6j was synthesized from
      maleic anhydride derivatives for development of new anticancer agents. The
      process involves the formation of pyridazine and phthalazine rings,
      dichlorination, allylthiolation, and aralkylthiolation. These new compounds
      showed antiproliferative activities against breast cancer (MCF-7) and
      hepatocarcinoma (Hep3B) cells in CCK-8 assays, and could be promising candidates
      for chemotherapy of carcinomas. Among 21 synthesized compounds, five compounds
      (5a, 5b, 6b, 6d, and 6f) showed higher potency than 5-FU for inhibiting the
      growth of cell line. The results indicated that compound 6f had the highest
      activity towards MCF-7 and Hep3B cells. These results suggest the potential
      anticancer activity of compounds 5a, 5b, 6b, 6d, and 6f.

PMID- 24925345
TI  - Failure of researchers, reviewers, editors, and the media to understand flaws in
      cancer screening studies: application to an article in Cancer.
AB  - Observational studies present inferential challenges. These challenges are acute
      in cancer screening studies, in which lead-time and length biases are ever
      present. These biases can make any study worthless. Moreover, a flawed study's
      impact on the public can be deleterious when its conclusions are publicized by a
      naive media. Flawed studies can also make the public learn to be wary of any
      article or reports of articles claiming to be scientific. Here, the author
      addresses these and related issues in the context of a study published in Cancer.

PMID- 24925346
TI  - The association between isolated oligohydramnios at term and pregnancy outcome.
AB  - PURPOSE: As conflicting data exist concerning the implications of isolated
      oligohydramnios on pregnancy outcome at term, we aimed to assess this association
      in low-risk pregnancies. METHODS: A retrospective cohort study of term
      pregnancies with sonographic finding of isolated oligohydramnios (amniotic fluid
      index (AFI) <5 cm) between 2007 and 2012. Outcome was compared to a control group
      of pregnancies with normal AFI (5-25 cm). Pregnancies complicated by
      thrombophilia, hypertension, diabetes, deviant fetal growth or
      chromosomal/structural abnormalities were excluded. Composite adverse outcome
      included CS/operative delivery due to non-reassuring heart rate (NRFHR), low
      Apgar score, umbilical artery pH < 7.10, neonatal intensive care admission,
      meconium aspiration syndrome, intubation or hypoxic-ischemic encephalopathy.
      RESULTS: Overall, 987 pregnancies complicated by isolated oligohydramnios were
      compared to 22,280 low-risk pregnancies with normal AFI. Isolated oligohydramnios
      was associated with a higher rate of induction of labor (27.7 vs. 3.7 %, p <
      0.001), CS due to NRFHR (2.3 vs. 1.1 %, p < 0.01) and composite adverse outcome
      (9.7 vs. 7.1 %, p < 0.01). However, after adjusting for potential confounders as
      induction of labor and nulliparity using multivariable logistic regression
      analysis, isolated oligohydramnios was not found to be independently associated
      with increased risk for composite adverse outcome (OR 1.01, 95 % CI 0.80-1.27, p
      = 0.93). CONCLUSION: Isolated oligohydramnios at term by itself is not associated
      with increased obstetrical morbidity.

PMID- 24925347
TI  - Platelet indices in patients with unexplained recurrent miscarriage: related
      factors should be considered.

PMID- 24925348
TI  - Response to: Platelet indices in patients with unexplained recurrent miscarriage;
      related factors should be considered.

PMID- 24925349
TI  - Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer,
      NCCTG/Alliance N0147.
AB  - BACKGROUND: KRAS and BRAF (V600E) mutations are important predictive and
      prognostic markers, respectively, in colon cancer, but little is known about
      patient and clinical factors associated with them. METHODS: Two thousand three
      hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for
      stage III colon cancer completed a patient questionnaire. Primary tumors were
      assessed for KRAS and BRAF (V600E) mutations and defective mismatch repair (dMMR)
      status. Logistic regression models and categorical data analysis were used to
      identify associations of patient and tumor characteristics with mutation status.
      All statistical tests were two-sided. RESULTS: KRAS (35%) and BRAF (V600E) (14%)
      mutations were nearly mutually exclusive. KRAS mutations were more likely to be
      present in patients without a family history of colon cancer and never smokers.
      Tumors with KRAS mutations were less likely to have dMMR (odds ratio [OR] = 0.21;
      95% confidence interval [CI] = 0.15 to 0.31; P < .001) and high-grade histology
      (OR = 0.73; 95% CI = 0.59 to 0.92; P < .001) but were more often right-sided.
      Among KRAS-mutated tumors, those with a Gly13Asp mutation tended to have dMMR and
      high-grade histology. Tumors with BRAF (V600E) mutations were more likely to be
      seen in patients who were aged 70 years or older (OR = 3.33; 95% CI = 2.50 to
      4.42; P < .001) and current or former smokers (OR = 1.64; 95% CI = 1.26 to 2.14;
      P < .001) but less likely in non-whites and men. Tumors with BRAF (V600E)
      mutations were more likely to be right-sided and to have four or more positive
      lymph nodes, high-grade histology, and dMMR. CONCLUSIONS: Specific patient and
      tumor characteristics are associated with KRAS and BRAF (V600E) mutations.

PMID- 24925351
TI  - NO147: the Giving Tree.

PMID- 24925350
TI  - Effects of Helicobacter pylori treatment on gastric cancer incidence and
      mortality in subgroups.
AB  - Among 2258 Helicobacter pylori-seropositive subjects randomly assigned to receive
      one-time H. pylori treatment with amoxicillin-omeprazole or its placebo, we
      evaluated the 15-year effect of treatment on gastric cancer incidence and
      mortality in subgroups defined by age, baseline gastric histopathology, and post
      treatment infection status. We used conditional logistic and Cox regressions for
      covariable adjustments in incidence and mortality analyses, respectively.
      Treatment was associated with a statistically significant decrease in gastric
      cancer incidence (odds ratio = 0.36; 95% confidence interval [CI] = 0.17 to 0.79)
      and mortality (hazard ratio = 0.26; 95% CI = 0.09 to 0.79) at ages 55 years and
      older and a statistically significant decrease in incidence among those with
      intestinal metaplasia or dysplasia at baseline (odds ratio = 0.56; 95% CI = 0.34
      to 0.91). Treatment benefits for incidence and mortality among those with and
      without post-treatment infection were similar. Thus H. pylori treatment can
      benefit older members and those with advanced baseline histopathology, and
      benefits are present even with post-treatment infection, suggesting treatment can
      benefit an entire population, not just the young or those with mild
      histopathology. 

PMID- 24925352
TI  - Prevention of gastric cancer with antibiotics: can it be done without eradicating
      Helicobacter pylori?

PMID- 24925353
TI  - Harmonic scalpel compared with conventional excisional haemorrhoidectomy: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Haemorrhoidectomy is the most effective and definitive treatment for
      grade 3 or 4 haemorrhoids despite being associated with considerable pain. The
      aim of this study was to search the literature, which compares outcomes of
      harmonic scalpel haemorrhoidectomy and traditional surgical procedures, and
      conduct a quantitative meta-analysis of the randomized trials. METHODS:
      Randomized controlled trials (RCTs) were identified from the major electronic
      databases using the keywords "harmonic scalpel haemorrhoidectomy" and
      "haemorrhoidectomy" and a quantitative meta-analysis conducted. The eight trials
      that met the inclusion criteria included 468 patients (233 in the harmonic
      scalpel group). Pain was the primary outcome measure, and other parameters
      assessed included duration of operation, length of hospital stay, time to return
      to work, and complications. RESULTS: Significantly, more patients returned to
      work in the first post-operative week, and pain scores were an average of one
      unit lower following harmonic scalpel haemorrhoidectomy. Generally, the incidence
      of complications in the harmonic scalpel group was less than half that found in
      conventional haemorrhoidectomy. There was no significant difference between the
      groups as regards operating time or length of hospital stay. Recurrence was not
      reported in any of the studies. CONCLUSIONS: The meta-analysis showed that
      harmonic scalpel haemorrhoidectomy is a safe and effective modality associated
      with less post-operative pain and a more rapid return to work than traditional
      surgery for haemorrhoids. Statistical heterogeneity was high; thus, it may be too
      early to place complete confidence in these results. Further RCTs are required.

PMID- 24925354
TI  - Surgical strategies in the management of recurrent retrorectal tumours.
AB  - BACKGROUND: The aim of this study was to review a consecutive series of patients
      who had undergone excision of recurrent retrorectal tumours and propose surgical
      strategies to tackle such recurrences. METHODS: Patients were identified from a
      prospectively maintained database. Demographic details, preoperative imaging and
      pathology, intra- and post-operative problems and follow-up details were noted.
      RESULTS: Fifteen patients (11 females) with a median age of 38 years (range 19-75
      years) underwent excision of recurrent retrorectal tumours (13 benign) between
      2002 and 2012. The median interval between the first and second surgical
      procedure was 3.5 years (range 1-19 years). Three patients had surgery performed
      via the transperineal approach, while 12 patients had resection via the abdominal
      approach. En bloc resection of adjacent organs was needed in three patients.
      Major pelvic bleeding occurred in two patients. R0 resection was achieved in all
      15 patients, and there have been no subsequent recurrences [median follow-up 73
      months (range 12-148 months)]. CONCLUSIONS: Benign recurrent retrorectal tumours
      can be safely excised usually without sacrifice of adjacent organs, while en bloc
      resection is needed for malignant tumours.

PMID- 24925355
TI  - Pediatric chest CT at 70 kVp: a feasibility study in 129 children.
AB  - BACKGROUND: Before introducing 70-kVp settings in the low-kilovoltage strategies
      for pediatric examinations, it was mandatory to demonstrate, at similar dose
      levels, an equivalence of image quality at 70 kVp and 80 kVp. OBJECTIVE: To
      assess image quality of chest CT examinations acquired at 70 kVp in comparison
      with standard scanning at 80 kVp. MATERIALS AND METHODS: We prospectively
      evaluated 129 children with a 70-kVp scanning protocol (group 1). All scanning
      parameters were kept similar to those usually selected for pediatric standard 80
      kVp protocols, except the milliamperage increased by a factor of 1.6 to maintain
      comparable radiation dose. Image quality of group 1 examinations was compared to
      that of a paired population scanned at 80 kVp (group 2). The noninferiority
      hypothesis was fixed at 10% of the mean level of image noise. RESULTS: There was
      no significant difference in the mean dose length product (DLP) and the volume
      computed tomography dose index (CTDIvol) between the groups (DLP: 20.5 +/- 5.8
      mGy.cm [group 1] vs. 19.7 +/- 7.6 mGy.cm [group 2]; P = 0.06) (CTDIvol: 0.8 +/-
      0.1 mGy [group 1] vs. 0.8 +/- 0.18 mGy [group 2]; P = 0.94). The mean of
      differences in image noise between group 1 and group 2 examinations was -1.38 (
      2.59; -0.18), verifying the noninferiority hypothesis. Subjective image quality
      did not significantly differ between group 1 and group 2 examinations (P = 0.18).
      CONCLUSION: At equivalent radiation dose levels, 70-kVp protocols provide similar
      image quality to that achievable at 80 kVp.

PMID- 24925356
TI  - Honey loading for pollen collection: regulation of crop content in honeybee
      pollen foragers on leaving hive.
AB  - Before foraging honeybees leave the hive, each bee loads its crop with some
      amount of honey "fuel" depending on the distance to the food source and foraging
      experience. For pollen collection, there is evidence that foragers carry
      additional honey as "glue" to build pollen loads. This study examines whether
      pollen foragers of the European honeybee Apis mellifera regulate the size of the
      crop load according to food-source distances upon leaving the hive and how
      foraging experience affects load regulation. The crop contents of bees foraging
      on crape myrtle Lagerstroemia indica, which has no nectary, were larger than
      those foraging on nectar from other sources, confirming a previous finding that
      pollen foragers carry glue in addition to fuel honey from the hive. Crop contents
      of both waggle dancers and dance followers showed a significant positive
      correlation with waggle-run durations. These results suggest that bees carry a
      distance-dependent amount of fuel honey in addition to a fixed amount of glue
      honey. Crop contents on leaving the hive were statistically larger in dancers
      than followers. Based on these results, we suggest that pollen foragers use
      information obtained through foraging experience to adjust crop contents on
      leaving the hive. 

PMID- 24925357
TI  - Evidence for early intracellular accumulation of volatile compounds during spadix
      development in Arum italicum L. and preliminary data on some tropical Aroids.
AB  - Staining and histochemistry of volatile organic compounds (VOCs) were performed
      at different inflorescence developmental stages on nine aroid species; one
      temperate, Arum italicum and eight tropical from the genera Caladium,
      Dieffenbachia and Philodendron. Moreover, a qualitative and quantitative analysis
      of VOCs constituting the scent of A. italicum, depending on the stage of
      development of inflorescences was also conducted. In all nine species, vesicles
      were observed in the conical cells of either the appendix or the stamens (thecae)
      and the staminodes. VOCs were localised in intracellular vesicles from the early
      stages of inflorescence development until their release during receptivity of
      gynoecium. This localisation was observed by the increase of both number and
      diameter of the vesicles during 1 week before receptivity. Afterwards, vesicles
      were fewer and smaller but rarely absent. In A. italicum, staining and gas
      chromatography analyses confirmed that the vesicles contained terpenes. The
      quantitatively most important ones were the sesquiterpenes, but monoterpenes were
      not negligible. Indeed, the quantities of terpenes matched the vesicles' size
      evolution during 1 week. Furthermore, VOCs from different biosynthetic pathways
      (sesquiterpenes and alkanes) were at their maximum quantity 2 days before
      gynoecium receptivity (sesquiterpenes and alkanes) or during receptivity
      (isobutylamine, monoterpenes, skatole and p-cresol). VOCs seemed to be emitted
      during gynoecium receptivity and/or during thermogenesis, and FADs are
      accumulated after thermogenesis in the spadix. These complex dynamics of the
      different VOCs could indicate specialisation of some VOCs and cell machinery to
      attract pollinators on the one hand and to repulse/protect against phytophagous
      organisms and pathogens after pollination on the other hand. 

PMID- 24925360
TI  - ABA renewal involves enhancements in both GluA2-lacking AMPA receptor activity
      and GluA1 phosphorylation in the lateral amygdala.
AB  - Fear renewal, the context-specific relapse of fear following fear extinction, is
      a leading animal model of post-traumatic stress disorders (PTSD) and fear-related
      disorders. Although fear extinction can diminish fear responses, this effect is
      restricted to the context where the extinction is carried out, and the
      extinguished fear strongly relapses when assessed in the original acquisition
      context (ABA renewal) or in a context distinct from the conditioning and
      extinction contexts (ABC renewal). We have previously identified Ser831
      phosphorylation of GluA1 subunit in the lateral amygdala (LA) as a key molecular
      mechanism for ABC renewal. However, molecular mechanisms underlying ABA renewal
      remain to be elucidated. Here, we found that both the excitatory synaptic
      efficacy and GluA2-lacking AMPAR activity at thalamic input synapses onto the LA
      (T-LA synapses) were enhanced upon ABA renewal. GluA2-lacking AMPAR activity was
      also increased during low-threshold potentiation, a potential cellular substrate
      of renewal, at T-LA synapses. The microinjection of 1-naphtylacetyl-spermine
      (NASPM), a selective blocker of GluA2-lacking AMPARs, into the LA attenuated ABA
      renewal, suggesting a critical role of GluA2-lacking AMPARs in ABA renewal. We
      also found that Ser831 phosphorylation of GluA1 in the LA was increased upon ABA
      renewal. We developed a short peptide mimicking the Ser831-containing C-tail
      region of GluA1, which can be phosphorylated upon renewal (GluA1S); thus, the
      phosphorylated GluA1S may compete with Ser831-phosphorylated GluA1. This GluA1S
      peptide blocked the low-threshold potentiation when dialyzed into a recorded
      neuron. The microinjection of a cell-permeable form of GluA1S peptide into the LA
      attenuated ABA renewal. In support of the GluA1S experiments, a GluA1D peptide
      (in which the serine at 831 is replaced with a phosphomimetic amino acid,
      aspartate) attenuated ABA renewal when microinjected into the LA. These findings
      suggest that enhancements in both the GluA2-lacking AMPAR activity and GluA1
      phosphorylation at Ser831 are required for ABA renewal. 

PMID- 24925361
TI  - Zingiberene attenuates hydrogen peroxide-induced toxicity in neuronal cells.
AB  - In this experimental design, we explored the neuroprotective potential of
      zingiberene (ZGB), a monocyclic sesquiterpene, in hydrogen peroxide (H2O2)
      induced toxicity in newborn rat cerebral cortex cell cultures for the first time.
      The rats were exposed to H2O2 for 6 h to determine the oxidative stress levels.
      To evaluate cell viability, both 3-(4,5-dimethylthiazole-2-yl)-2,5
      diphenyltetrazolium bromide and lactate dehydrogenase assays were carried out.
      Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were
      used to evaluate oxidative changes. Besides determining 8-hydroxy-2
      deoxyguanosine (8-OH-dG) levels in vitro, single-cell gel electrophoresis was
      also performed to measure the resistance of neuronal DNA to H2O2- exposed rats.
      Our results showed that survival and TAC levels of the cells decreased, while
      TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA
      damage increased in the H2O2 alone-treated cultures. But pretreatment of ZGB
      suppressed the cytotoxicity, genotoxicity and oxidative stress that were
      increased by H2O2. Based on these observations, it is suggested that the
      sesquiterpene ZGB can be used as a novel and natural potential therapeutic in
      counteracting oxidative damages in the field of neurodegenerative disorders. 

PMID- 24925362
TI  - Mechanisms of resveratrol-induced changes in cytosolic free calcium ion
      concentrations and cell viability in OC2 human oral cancer cells.
AB  - Resveratrol is a natural compound that affects cellular calcium (Ca(2+))
      homeostasis and viability in different cells. This study examined the effect of
      resveratrol on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in
      OC2 human oral cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used
      to measure [Ca(2+)]i, and water-soluble tetrazolium-1 was used to measure
      viability. Resveratrol evoked concentration-dependent increase in [Ca(2+)]i. The
      response was reduced by removing extracellular Ca(2+). Resveratrol also caused
      manganese-induced fura-2 fluorescence quench. Resveratrol-evoked Ca(2+) entry was
      inhibited by nifedipine and the protein kinase C (PKC) inhibitor GF109203X but
      was not altered by econazole, SKF96365, and the PKC activator phorbol 12
      myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic
      reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished
      resveratrol-evoked [Ca(2+)]i rise. Conversely, treatment with resveratrol
      inhibited BHQ-evoked [Ca(2+)]i rise. Inhibition of phospholipase C (PLC) with
      U73122 abolished resveratrol-evoked [Ca(2+)]i rise. At 20-100 MUM, resveratrol
      decreased cell viability, which was not affected by chelating cytosolic
      Ca(2+)with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl
      ester. Annexin V-fluorescein isothiocyanate staining data suggest that
      resveratrol at 20-40 MUM induced apoptosis in a concentration-dependent manner.
      Collectively, in OC2 cells, resveratrol induced [Ca(2+)]i rise by evoking PLC
      dependent Ca(2+) release from the endoplasmic reticulum and by causing Ca(2+)
      entry via nifedipine-sensitive, PKC-regulated mechanisms. Resveratrol also caused
      Ca(2+)-independent apoptosis. 

PMID- 24925364
TI  - Induction of sister chromatid exchanges and cell division delays by clomiphene
      citrate in human lymphocytes.
AB  - OBJECTIVE: Clomiphene citrate (CC) is a selective estrogen receptor modulator and
      is used for the treatment of in vitro fertilization, intracytoplasmic sperm
      injection, intrauterine insemination, and so on. In this study, sister chromatid
      exchanges (SCEs) and cell cycle delays were analyzed to investigate genotoxicity
      and cytotoxicity of CC in peripheral blood lymphocytes of healthy women. METHODS:
      Human peripheral blood lymphocytes obtained from two donors were used to detect
      genotoxicity and cytotoxicity of CC. Lymphocytes were treated with various
      concentrations (0.40, 0.80, 1.60, and 3.20 ug/ml) of CC. A negative (distilled
      water) and a positive control (mitomycin-C = 0.20 ug/ml) were also used
      simultaneously with test substance-treated cultures. SCEs and cell division
      delays were measured from 25 cells and 100 cells perdonor, respectively. RESULTS:
      CC significantly increased the mean SCE value at all concentrations compared with
      the negative control. This increase was found to be dose dependent (r = 0.83) and
      at the highest concentration, nearly two times higher increase was observed than
      the negative control. However, replication index was not affected by the CC
      treatment. CONCLUSION: The present study shows that CC is genotoxic for human
      lymphocytes in vitro. Further investigations, especially in vivo are now needed
      in different test organisms to clarify the genotoxic activity of CC, which should
      also help to better understand genotoxic mechanism of this ovulation-stimulating
      drug.

PMID- 24925363
TI  - In vivo radioadaptive response: a review of studies relevant to radiation-induced
      cancer risk.
AB  - Radioadaptive response (RAR) describes phenomena where small conditioning doses
      of ionizing radiation (IR) reduce detrimental effects of subsequent higher IR
      doses. Current radiation protection regulations do not include RAR because of the
      large variability in expression among individuals and uncertainties of the
      mechanism. However, RAR should be regarded as an indispensable factor for
      estimation and control of individual IR sensitivity. In this article, RAR studies
      relevant to individual cancer risk are reviewed. Using various stains of mice,
      carcinogenic RAR has been demonstrated. Consistently much in vivo evidence for
      RAR with end points of DNA and chromosome damage is reported. Most in vivo RAR
      studies revealed efficient induction of RAR by chronic or repeated low-dose
      priming irradiation. Chronic IR-induced RAR was observed also in human
      individuals after environmental, occupational, and nuclear accident radiation
      exposure. These observations may be associated with an intrinsically distinct
      feature of in vivo experimental systems that mainly consist of nonproliferating
      mature cells. Alternatively, induction of RAR by gap junction-mediated bystander
      effects suggests that multicellular systems comprising densely communicating
      cells may be capable of responding to long-lasting low-dose-rate priming
      irradiation. Regulation by endocrine factors is also a plausible mechanism for
      RAR at an individual level. Emerging evidence suggests that glucocorticoids,
      known as stress hormones, participate in in vivo RAR induction following long
      term low-dose-rate exposure to IR. 

PMID- 24925365
TI  - Electron microscopic examination of effects of bogma raki and walnut on cochlea:
      an experimental study.
AB  - Illegal alcohol beverages known as bogma raki in our country are consumed widely
      in our region. The studies investigating the relationship between alcohol
      consumption and hearing ability report different results. In this study, we aimed
      to investigate the toxic effects of bogma raki that contains neurotoxic
      substances on cochlea by electron microscopy. To the best of our knowledge, this
      study is the first in the literature. A total of 48 Wistar male albino rats (aged
      12-16 weeks and weighing 200-240 g) were used in the study. The rats were divided
      into 4 groups with 12 animals in each group. The groups include control, bogma
      raki, walnut, and walnut + bogma raki groups. Bogma raki (30% v/v, 9.2 ml kg(-1)
      day(-1)) is added to drinking water of rats in bogma raki group (n = 12) for 4
      weeks. Walnut group rats (n = 12) are fed with standard rat food and walnut
      without limitation (10 g kg(-1) day(-1)). Bogma raki + walnut group rats (n = 12)
      are fed with standard rat food and walnut and bogma raki is added to drinking
      water. The cochleas were dissected and removed en bloc and examined by electron
      microscopy. Perineuronal oedema around neurons of spiral ganglion and hairy cells
      of organ of Corti were present in the bogma raki group, walnut group and bogma
      raki + walnut group under electron microscopic examination. Comparing these three
      groups, there were no differences in the ultrastructural pathological changes. In
      the ultrastructural examination of the myelinated axons forming cochlear nerve,
      no ultrastructural pathology was detected in all the groups. 

PMID- 24925366
TI  - Carbon monoxide poisoning and intracardiac thrombus formation: additional
      mechanisms.

PMID- 24925367
TI  - Aspartame induces angiogenesis in vitro and in vivo models.
AB  - Angiogenesis is the process of generating new blood vessels from preexisting
      vessels and is considered essential in many pathological conditions. The purpose
      of the present study is to evaluate the effect of aspartame on angiogenesis in
      vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in
      vitro 2,3-bis-2H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In
      CAM assay, aspartame increased angiogenesis in a concentration-dependent manner.
      Compared with the control group, aspartame has significantly increased vessel
      proliferation (p < 0.001). In addition, in vivo rat model of skin wound-healing
      study showed that aspartame group had better healing than control group, and this
      was statistically significant at p < 0.05. There was a slight proliferative
      effect of aspartame on human umbilical vein endothelial cells on XTT assay in
      vitro, but it was not statistically significant; and there was no antiangiogenic
      effect of aspartame on tube formation assay in vitro. These results provide
      evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use
      may have undesirable effect on susceptible cases. 

PMID- 24925368
TI  - Protective effects of saffron (its active constituent, crocin) on nephropathy in
      streptozotocin-induced diabetic rats.
AB  - The reactive oxygen species take role in pathogenesis of many diseases including
      hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension,
      ischemia-reperfusion damage, and heart defects. The aim of this study was to
      evaluate whether crocin administration could protect kidney injury from oxidative
      stress in streptozotocin-induced diabetic rats. The rats were randomly divided
      into 3 groups each containing 10 animals as follows: group 1, control group;
      group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end
      of the study, trunk blood was collected to determine the plasma levels of blood
      urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and
      biochemical and histological changes were examined. Diabetes caused a significant
      increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a
      decrease in glutathione (GSH) contents (p < 0.01) when compared with control
      group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (p
      < 0.01) and XO (p < 0.05) activities and elevated GSH (p < 0.05) contents when
      compared with DM group. Plasma levels of BUN and Cr were significantly higher in
      the DM group when compared with the control group (p < 0.01). Pretreatment of the
      DM animals with crocin decreased the high level of serum Cr and BUN. Control
      group was normal in histological appearance, but congestion, severe inflammation,
      tubular desquamation, tubular necrosis, and hydropic degeneration in tubular
      cells were observed in the DM group. Histopathological changes markedly reduced,
      and appearance of kidney was nearly similar to control group in DM + crocin
      group. Our results show that crocin could be beneficial in reducing diabetes
      induced renal injury.

PMID- 24925369
TI  - Polyunsaturated fatty acid intake and risk of lung cancer: a meta-analysis of
      prospective studies.
AB  - BACKGROUND: Studies have reported inconsistent results for the existence of an
      association between polyunsaturated fatty acid (PUFA) intake and risk of lung
      cancer. The purpose of this study is to summarize the evidence regarding this
      relationship using a dose response meta-analytic approach. METHODOLOGY AND
      PRINCIPAL FINDINGS: We searched the PubMed, EmBase, and Cochrane Library
      electronic databases for related articles published through July 2013. Only
      prospective studies that reported effect estimates with 95% confidence intervals
      (CIs) of lung cancer incidence for greater than 2 categories of PUFA intake were
      included. We did random-effects meta-analyses of study-specific incremental
      estimates to determine the risk of lung cancer associated with a 5 g per day
      increase in PUFA intake. Overall, we included 8 prospective cohort studies
      reporting data on 1,268,442 individuals. High PUFA intake had little or no effect
      on lung cancer risk (risk ratio [RR], 0.91; 95% CI, 0.78-1.06; P = 0.230).
      Furthermore, the dose-response meta-analysis also suggested that a 5 g per day
      increase in PUFA has no significant effect on the risk of lung cancer (RR, 0.98;
      95%CI: 0.96-1.01; P = 0.142). Finally, the findings of dose response curve
      suggested that PUFA intake of up to 15 g/d seemed to increase the risk of lung
      cancer. Furthermore, PUFA intake greater than 15 g/d was associated with a small
      beneficial effect and borderline statistical significance. Subgroup analyses for
      5 g per day increment in PUFA indicated that the protective effect of PUFA was
      more evident in women (RR, 0.94; 95% CI, 0.87-1.01; P = 0.095) than in men (RR,
      1.00; 95% CI, 0.98-1.02; P = 0.784). CONCLUSION/SIGNIFICANCE: Our study indicated
      that PUFA intake had little or no effect on lung cancer risk. PUFA intake might
      play an important role in lung cancer prevention in women.

PMID- 24925370
TI  - The role of the SHH gene in prostate cancer cell resistance to paclitaxel.
AB  - BACKGROUND: The increased activity of the Sonic Hedgehog (SHH) pathway has been
      demonstrated in many types of cancer including prostate cancer (PCa). It has been
      shown that SHH pathway is involved in tumor angiogenesis and in regulation of
      metabolism of cancer stem cells. The increased activity of the SHH pathway is
      responsible for generation and maintenance of the multidrug resistance in cancer
      cells. A key role in the development of this insensitivity to cytotoxic drugs
      play ATP-binding cassette (ABC) transporters. METHODS: SHH encoding plasmid was
      stably transfected into PCa cell lines DU145 and LNCaP. The expression of SHH was
      silenced by shRNA and the level of SHH was tested by quantitative (q)PCR and
      western blot methods. The effect of SHH overexpression in cells after treatment
      with paclitaxel was measured by MTT assay, crystal violet assay and flow
      cytometry. The level of 44 ABC transporters was estimated by qPCR. RESULTS:
      Expression of exogenous SHH protein in DU145 and LNCaP cell lines enhanced their
      resistance to paclitaxel along with increased expression of ABC transporters
      transcripts. Paclitaxel treatment further enhanced the expression of increased
      ABC transporters transcripts in cells overexpressing SHH. CONCLUSIONS:
      Overexpression of SHH enhances PCa cell lines resistance to paclitaxel. Higher
      level of SHH leads to increase in ABC transporters expression in a manner
      dependent on paclitaxel.

PMID- 24925371
TI  - Combined influence of visual scene and body tilt on arm pointing movements:
      gravity matters!
AB  - Performing accurate actions such as goal-directed arm movements requires taking
      into account visual and body orientation cues to localize the target in space and
      produce appropriate reaching motor commands. We experimentally tilted the body
      and/or the visual scene to investigate how visual and body orientation cues are
      combined for the control of unseen arm movements. Subjects were asked to point
      toward a visual target using an upward movement during slow body and/or visual
      scene tilts. When the scene was tilted, final pointing errors varied as a
      function of the direction of the scene tilt (forward or backward). Actual forward
      body tilt resulted in systematic target undershoots, suggesting that the brain
      may have overcompensated for the biomechanical movement facilitation arising from
      body tilt. Combined body and visual scene tilts also affected final pointing
      errors according to the orientation of the visual scene. The data were further
      analysed using either a body-centered or a gravity-centered reference frame to
      encode visual scene orientation with simple additive models (i.e., 'combined'
      tilts equal to the sum of 'single' tilts). We found that the body-centered model
      could account only for some of the data regarding kinematic parameters and final
      errors. In contrast, the gravity-centered modeling in which the body and visual
      scene orientations were referred to vertical could explain all of these data.
      Therefore, our findings suggest that the brain uses gravity, thanks to its
      invariant properties, as a reference for the combination of visual and non-visual
      cues. 

PMID- 24925372
TI  - A feasible strategy for preventing blood clots in critically ill patients with
      acute kidney injury (FBI): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Previous pharmacokinetic trials suggested that 40 mg subcutaneous
      enoxaparin once daily provided inadequate thromboprophylaxis for intensive care
      unit patients. Critically ill patients with acute kidney injury are at increased
      risk of venous thromboembolism and yet are often excluded from these trials. We
      hypothesized that for critically ill patients with acute kidney injury receiving
      continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously
      once daily would improve thromboprophylaxis without increasing the risk of
      bleeding. In addition, we seek to utilize urine output prior to discontinuing
      dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free
      intervals, as markers of renal recovery. METHODS/DESIGN: In a multicenter, double
      blind randomized controlled trial in progress at three intensive care units
      across Denmark, we randomly assign eligible critically ill adults with acute
      kidney injury into a treatment (1 mg/kg enoxaparin subcutaneously once daily) or
      control arm (40 mg enoxaparin subcutaneously once daily) upon commencement of
      continuous renal replacement therapy.We calculated that with 133 patients in each
      group, the study would have 80% power to show a 40% reduction in the relative
      risk of venous thromboembolism with 1 mg/kg enoxaparin, at a two-sided alpha
      level of 0.05. An interim analysis will be conducted after the first 67 patients
      have been included in each group.Enrolment began in March 2013, and will continue
      for two years. The primary outcome is the occurrence of venous thromboembolism.
      Secondary outcomes include anti-factor Xa activity, bleeding, heparin-induced
      thrombocytopenia, filter lifespan, length of stay, ventilator free days, and
      mortality. We will also monitor neutrophil gelatinase-associated lipocalin and
      urine volume to determine whether they can be used as prognostic factors for
      renal recovery. DISCUSSION: Critically ill unit patients with acute kidney injury
      present a particular challenge in the provision of thromboprophylaxis. This study
      hopes to add to the growing evidence that the existing recommendation of 40 mg
      enoxaparin is inadequate and that 1 mg/kg is both safe and effective for
      thromboprophylaxis.In addition, the study seeks to identify predictors of renal
      recovery allowing for the proper utilization of resources. TRIAL REGISTRATION: EU
      Clinical Trials Register: EudraCT number: 2012-004368-23, 25 September 2012.

PMID- 24925373
TI  - Overexpression of erg1 gene in Trichoderma harzianum CECT 2413: effect on the
      induction of tomato defence-related genes.
AB  - AIMS: To investigate the effect of the overexpression of erg1 gene of Trichoderma
      harzianum CECT 2413 (T34) on the Trichoderma-plant interactions and in the
      biocontrol ability of this fungus. METHODS AND RESULTS: Transformants of T34
      strain overexpressing erg1 gene did not show effect on the ergosterol level,
      although a drastic decrease in the squalene level was observed in the
      transformants at 96 h of growth. During interaction with plants, the erg1
      overexpression resulted in a reduction of the priming ability of several tomato
      defence-related genes belonging to the salicylate pathway, and also of the
      TomLoxA gene, which is related to the jasmonate pathway. Interestingly, other
      jasmonate-related genes, such as PINI and PINII, were slightly induced. The erg1
      overexpressed transformants also showed a reduced ability to colonize tomato
      roots. CONCLUSIONS: The ergosterol biosynthetic pathway might play an important
      role in regulating Trichoderma-plant interactions, although this role does not
      seem to be restricted to the final product; instead, other intermediates such as
      squalene, whose role in the Trichoderma-plant interaction has not been
      characterized, would also play an important role. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The functional analysis of genes involved in the synthesis of ergosterol
      could provide additional strategies to improve the ability of biocontrol of the
      Trichoderma strains and their interaction with plants.

PMID- 24925375
TI  - A mechanistic change results in 100 times faster CH functionalization for ethane
      versus methane by a homogeneous Pt catalyst.
AB  - The selective, oxidative functionalization of ethane, a significant component of
      shale gas, to products such as ethylene or ethanol at low temperatures and
      pressures remains a significant challenge. Herein we report that ethane is
      efficiently and selectively functionalized to the ethanol ester of H2SO4, ethyl
      bisulfate (EtOSO3H) as the initial product, with the Pt(II) "Periana-Catalytica"
      catalyst in 98% sulfuric acid. A subsequent organic reaction selectively
      generates isethionic acid bisulfate ester (HO3S-CH2-CH2-OSO3H, ITA). In contrast
      to the modest 3-5 times faster rate typically observed in electrophilic CH
      activation of higher alkanes, ethane CH functionalization was found to be ~100
      times faster than that of methane. Experiment and quantum-mechanical calculations
      reveal that this unexpectedly large increase in rate is the result of a
      fundamentally different catalytic cycle in which ethane CH activation (and not
      platinum oxidation as for methane) is now turnover limiting. Facile Pt(II)-Et
      functionalization was determined to occur via a low energy beta-hydride
      elimination pathway (which is not available for methane) to generate ethylene and
      a Pt(II)-hydride, which is then rapidly oxidized by H2SO4 to regenerate Pt(II)
      X2. A rapid, non-Pt-catalyzed reaction of formed ethylene with the hot,
      concentrated H2SO4 solvent cleanly generate EtOSO3H as the initial product, which
      further reacts with the H2SO4 solvent to generate ITA.

PMID- 24925374
TI  - Contrast-enhanced ultrasound-guided Sentinel lymph node biopsy of the ocular
      conjunctiva.
AB  - OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy (SLNB) has been utilized for
      cutaneous melanoma and other malignancies arising from the eye and ocular adnexa.
      Currently, SLNB requires blue dyes and/or radiopharmaceuticals; both of which
      have significant shortcomings. This study sought to evaluate the feasibility of
      SLNB with the use of real-time, contrast-enhanced ultrasound (CEUS) as an
      alternative technique for tumors arising in the conjunctiva. STUDY DESIGN:
      Prospective feasibility study in a porcine model. METHODS: Twelve experiments
      were performed on six non-tumor-bearing Yorkshire swine. An ultrasound contrast
      agent, Sonazoid (GE Healthcare, Oslo, Norway), (99m) technetium ((99m) Tc), and
      methylene blue (MB) (Covidien, Mansfield, MA) were injected in the ocular
      conjunctiva. Sentinel lymph nodes (SLNs) were localized with CEUS and findings
      were compared to that of MB and (99m) Tc. Fisher exact test was used. RESULTS:
      Contrast-enhanced SLNs were identified within an average of 6.2 minutes from time
      of injection of Sonazoid. A total of 17 SLNs were identified by at least one of
      the three techniques. Correlation between Sonazoid and (99m) Tc was 94.1% (16/17
      SLNs). Correlation between (99m) Tc and MB was 88.2% (15/17). One SLN that was
      positive for (99m) Tc but negative for Sonazoid and was considered to be a false
      positive (1/17); findings were similar for MB (1/17). Differences between the
      three techniques were not significant (P = .886). CONCLUSIONS: CEUS-guided
      injection of conjunctiva for SLNB is technically feasible and correlates well
      with standard detection techniques. This technique shows promise for rapid, real
      time, intraoperative imaging for SLNB, using a widely available imaging modality
      and avoiding the need for radiopharmaceuticals. LEVEL OF EVIDENCE: NA

PMID- 24925376
TI  - Exogenous connective tissue growth factor preserves the hair-inductive ability of
      human dermal papilla cells.
AB  - Connective tissue growth factor influences human dermal papilla cells' hair
      inductive ability through several signaling pathways. 

PMID- 24925378
TI  - Stopping movements: when others slow us down.
AB  - Previous research has shown that performing joint actions can lead to the
      representation of both one's own and others' actions. In the present study we
      explored the influence of co-representation on response stopping. Are joint
      actions more difficult to stop than solo actions? Using a variation of the stop
      signal task, we found that participants needed more time to stop a planned joint
      action compared with a planned solo action (Experiment 1). This effect was not
      observed when participants performed the task in the presence of a passive
      observer (Experiment 2). A third transcranial magnetic stimulation experiment
      (Experiment 3) demonstrated that joint stopping recruited a more selective
      suppression mechanism than solo stopping. Taken together, these results suggest
      that participants used a global inhibition mechanism when acting alone; however,
      they recruited a more selective and slower suppression mechanism when acting with
      someone else. 

PMID- 24925379
TI  - History of allergy in antiquity.
AB  - Allergic diseases are not new. They have been described in the early medical
      literature in various cultures like Egypt, China, indigenous America and in the
      Greco-Roman tradition. The terms 'idiosyncrasy', 'asthma' and 'eczema' are still
      in use today. The most famous allergic individual of antiquity with the whole
      triad of atopic diseases and a positive family history of atopy probably was
      Emperor Octavianus Augustus.

PMID- 24925377
TI  - Amino acids and derivatives, a new treatment of chronic heart failure?
AB  - Amino acids play a key role in multiple cellular processes. Amino acids
      availability is reduced in patients with heart failure (HF) with deleterious
      consequences on cardiac and whole-body metabolism. Several metabolic
      abnormalities have been identified in the failing heart, and many of them lead to
      an increased need of amino acids. Recently, several clinical trials have been
      conducted to demonstrate the benefits of amino acids supplementation in patients
      with HF. Although they have shown an improvement of exercise tolerance and, in
      some cases, of left ventricular function, they have many limitations, namely
      small sample size, differences in patients' characteristics and nutritional
      supplementations, and lack of data regarding outcomes. Moreover recent data
      suggest that a multi-nutritional approach, including also antioxidants, vitamins,
      and metals, may be more effective. Larger trials are needed to ascertain safety,
      efficacy, and impact on prognosis of such an approach in HF. 

PMID- 24925380
TI  - History of allergy in the middle ages and renaissance.
AB  - In the Middle Ages little innovative medical literature came from Western Europe.
      The Greek-Roman tradition with the scriptures of Hippocrates and Galenos was
      preserved in Byzantium and then in the Middle East by Arabic medicine; it then
      returned to Europe in Latin translations mostly made in Italy and Spain. There
      were innovative developments in Arabic medicine also with regard to the history
      of allergy, especially with the first description of 'rose fever', which is
      described as very similar in symptomatology to hay fever. Under Arabic influence,
      the first medical university in Salerno was famous for its well-known text
      Tacuinum sanitatis in which a description of asthma can be found. With the
      beginning of renaissance new developments were also registered in Europe, with
      new observations and a new way of thinking.

PMID- 24925381
TI  - Landmarks in Allergy during the 19th Century.
AB  - There were remarkable achievements in the 19th century in our understanding of
      the cells of the allergic response, the clear descriptions of hay fever and
      asthma, as well as the role of pollen in seasonal rhinitis. Although allergy as a
      concept was not developed until well into the 20th century, the foundations of
      our present understanding of these diseases were laid in the 1800s. The
      outstanding physicians and scientists of this time included Paul Ehrlich (who
      described mast cells, eosinophils and basophils), John Bostock (who provided the
      first detailed account of hay fever), Charles Blackley (who showed that pollen
      was the cause of hay fever), Morrill Wyman (who demonstrated that autumnal
      catarrh was due to ragweed pollen), Henry Hide Salter (who made the first classic
      description of asthma) and Henri Laennec (the inventor of the stethoscope).

PMID- 24925382
TI  - Milestones in the 20th century.
AB  - From its very beginning, the 20th century represented the period of the main
      breakthrough for allergology as a clinical and scientific entity. The first years
      of this period were extraordinarily exciting because of the discovery of the
      anaphylactic reaction in 1902 and its clinical diagnosis as 'local anaphylaxis',
      'serum sickness' (1903) or even as 'anaphylactic shock' (1907). The term
      'allergy' was coined in 1906 and led to the recognition of allergic diseases as a
      pathogenetic entity. The first patient organization of hay fever sufferers was
      founded in Germany in 1900, the same year in which the very first report on
      immunotherapy was published in New York. In 1911 the era of actual immunotherapy
      started in London, becoming scientific with the first double-blind study in 1956,
      and still today being regarded as the backbone of allergology. In 1919 it was
      shown that allergy could be transferred by blood, in 1921 by serum (Prausnitz
      Kustner test) and in 1966 the mystic 'reagins' were recognized as immunoglobulin
      (Ig) E. The development of the radioallergosorbent test for quantifying specific
      IgE antibody was a diagnostic landmark for allergists all over the world. The
      history of allergy diagnosis started with the introduction of a 'functional skin
      test', named the patch test in 1894. The scratch test was described in 1912 and
      the patch test in 1931. From 1908 the skin was tested by intracutaneous
      injections, and from 1930 by a 'puncture test' (a precursor of the prick test)
      which has been in worldwide use in modified variations since 1959. The rub test
      ('friction test') was added in 1961. Systematically applied provocation tests
      started with conjunctival provocation (1907), followed by nasal and bronchial
      provocation with allergens (1914 and 1925).

PMID- 24925383
TI  - Terminology of allergic phenomena.
AB  - Over the last 2,000 years a variety of terms have been used for the description
      of phenomena possibly related to allergy. Many have been forgotten, while some of
      them have remained. In Greco-Roman literature the term 'idiosyncrasy' was used to
      describe an individual characterization of a health condition, possibly
      comparable to 'constitution'. The same term was also used to describe individual
      reaction patterns, and the term 'antipathy' was used in a similar sense.
      'Hypersensitivity' originated from the German word 'Uberempfindlichkeit' and was
      first used in a medical sense by Emil von Behring when he described untoward
      reactions to his antitoxin containing serum therapy. 'Anaphylaxis' was coined by
      Richet and Portier to describe the new phenomenon of a life-threatening general
      pathogenic reaction after repeated injection of antigen. In 1906, Clemens von
      Pirquet introduced the term 'allergy' in order to bring more clarity to the
      confusing debate regarding protective and harmful immunity. In order to
      characterize the familial occurrence of hypersensitivity reactions such as
      asthma, hay fever and others, the American allergists A.F. Coca and R.A. Cooke
      introduced the term 'atopy'. Contrary to anaphylaxis, which was experimentally
      induced, this type of 'hypersensitiveness' occurred spontaneously. The nature of
      the pathogenic factor was called the 'atopic reagin' and was found to be
      transferable with serum by Prausnitz and Kustner. After the detection of
      immunoglobulin (Ig) E as the carrier of this type of hypersensitivity, the term
      'atopy' gained a new sense, since IgE is a characteristic - yet not exclusive -
      parameter of the so-called atopic diseases. Clinically similar diseases such as
      asthma, rhinoconjunctivitis or eczema can be found in the absence of IgE, and are
      then called 'intrinsic' variants of the same disease.

PMID- 24925384
TI  - Anaphylaxis.
AB  - The term anaphylaxis was coined by Charles Richet and Paul Portier when they
      tried to immunize dogs with actinia extracts, but after a repeated injection of a
      small amount of the toxin the dog died within 25 min. The new term rapidly spread
      all over the world. The discovery of the phenomenon of anaphylaxis showed that by
      immunization not only protection but also harmful events could be induced. For
      this discovery Richet received the Nobel Prize in 1913, but he still believed the
      condition of anaphylaxis was a lack of protection to the poisonous effect of the
      substance. Already earlier similar clinical phenomena had been observed but not
      well described. A major breakthrough in understanding the pathophysiology came
      through the experiments of Dale and Laidlaw who showed that the newly discovered
      histamine was able to induce quite similar symptoms to anaphylaxis. For decades
      reactions mimicking anaphylaxis but without involvement of the immune systems
      were called 'anaphylactoid', 'allergy-like' or 'pseudo-allergic'. Since the new
      definition of the World Allergy Organization (WAO) anaphylaxis is defined on the
      basis of clinical symptoms independent of pathomechanisms involved: one
      distinguishes between allergic and non-immune anaphylaxis. Epinephrine
      (Adrenalin) was soon recognized as treatment of choice of this dramatic
      condition.

PMID- 24925385
TI  - Allergic rhinitis.
AB  - Allergic rhinitis is a very frequent disease with a prevalence of 15-20%.
      Symptoms are most pronounced in young people while, for some unknown reason, the
      elderly become clinically hyposensitized. Pollen is the cause of seasonal
      allergic rhinitis, and house dust mite and animals are the main causes of
      perennial allergic rhinitis. Histamine is the main cause of sneezing and
      hypersecretion, while other mediators probably also play a role in nasal
      blockage. In polyposis, a local denervation is an important cause of vascular
      leakage, edema and polyp formation. Antihistamines have a positive effect on
      sneezing and hypersecretion, but not on blockage. As they have a quick onset of
      action they are useful in patients with mild and occasional symptoms. A nasal
      steroid is preferable in patients with persistent symptoms, since it is more
      effective on all nasal symptoms. Short-term use of a systemic steroid can be a
      valuable adjunct to topical treatment, especially in nasal polyposis, when there
      is a temporary failure of topical treatment in a blocked nose. A nasal
      vasoconstrictor can be added for short-term treatment, and an ipratropium spray
      can be beneficial in perennial non-allergic rhinitis, when watery secretion is
      the dominant symptom. Immunotherapy can be added in allergic rhinitis, when
      pharmacotherapy is insufficient. This chapter is based on the author's personal
      experience with allergic rhinitis, as a patient, a doctor and a researcher.
      Therefore, it is not a balanced review and the references will be highly selected
      as they largely consist of the author's own publications. As the text is mainly
      based on personal research, steroids are described in detail, while, with regard
      to immunotherapy, the reader is referred to another chapter. In addition to
      allergic rhinitis, nasal polyposis will be described. It was formerly believed to
      be an allergic disease, but we now know that it is not. However, with regard to
      histopathology and drug responsiveness this disease is very similar to allergic
      rhinitis.

PMID- 24925386
TI  - Asthma.
AB  - 'Asthma' is derived from the Greek root alphasigmathetaMUalphaiotanuomega,
      meaning 'gasp for breath'. The term originally did not define a disease, but was
      employed to describe respiratory symptoms of a variety of pulmonary conditions.
      Over the centuries, several models have been proposed to understand the
      pathophysiologic abnormalities of asthma. By the beginning of the 20th century,
      asthma was seen to be a unique illness characterized by 'spasmodic afflictions of
      the bronchial tubes'. Consistent with the nature of asthma as a complex disease,
      the models for asthma pathogenesis have become increasingly complex. Research has
      moved from antiquated ideas to a descriptive functional approach to one that
      relies on pathophysiology in cellular and molecular biology, immunology,
      microbiology and genetics/genomics. As more advanced technologies for measuring
      lung function were developed, the features of asthma were steadily unraveled and
      its pathophysiology clarified. Asthma was shown to be associated with transient
      increases in airway resistance, reductions in forced expiratory volumes and
      flows, hyperinflation of the lungs and increased work of breathing, as well as
      abnormalities in the distribution of ventilation, perfusion and arterial blood
      gases. Today, asthma is seen as a chronic inflammatory disease which is not yet
      fully understood in its pathophysiology; therefore, therapy is still on the path
      to becoming optimal.

PMID- 24925387
TI  - Atopic dermatitis/atopic eczema.
AB  - Atopic dermatitis was described in 1933 but exists since antiquity. We review
      descriptions of a childhood skin disease compatible with our modern diagnosis of
      atopic dermatitis, in ancient medicine and in nineteenth century dermatology
      texts. We identify Hebra's prurigo and Besnier's diathetic prurigo as forerunners
      of atopic dermatitis, the latter being a synthesis of infantile eczema and
      prurigo. The pathogenic theories which link atopic dermatitis to humoralistic
      medicine, to digestive diseases, to allergy may have had consequences on today's
      reluctance to consider atopic dermatitis as a skin disorder, the treatment of
      which relies mainly on topicals.

PMID- 24925388
TI  - Allergic contact dermatitis.
AB  - Allergic contact dermatitis is one of the most important dermatologic disorders
      worldwide - it can cause significant morbidity and decreased quality of life, as
      well as having major economic implications and loss of vocational productivity.
      Patch testing is the most important discovery in allergic contact dermatitis and
      the best diagnostic modality to date; the thin-layer rapid- use epicutaneous
      (TRUE) test is a more recent patch test development which has improved the
      convenience and feasibility of the test. The future of allergic contact
      dermatitis is bright as we continue to learn more about the science of the
      disorder, as well as ways to improve diagnosis and patient care. Furthermore, it
      is important to remember, in this global age, that cooperation between health
      care providers worldwide is essential.

PMID- 24925389
TI  - Urticaria and angioedema.
AB  - Urticaria and angioedema are ancient diseases. Many different names have been
      used to describe them, and many different theories have been postulated to
      explain their origin and pathogenesis. The current classification and
      nomenclature of urticaria and angioedema have evolved over several millennia,
      with many detours and problems, some of which still remain to be solved. This
      chapter describes the history of urticaria and angioedema. The evolution of
      selected aspects of today's understanding of both conditions is also traced,
      based on the review of original sources and previously published research on this
      topic.

PMID- 24925390
TI  - Allergy and the eye.
AB  - This review of the major milestones in the history of ocular allergy and
      immunology shows how significantly this subdiscipline has contributed to the
      tremendous progress in the understanding of mechanisms of allergic and
      immunologic diseases, as well as in their better management. It also indicates
      unmet needs and priority areas for future research.

PMID- 24925391
TI  - History of food allergy.
AB  - In this chapter we will first consider whether there is real evidence on the
      basis of literature for early descriptions in antiquity of pathogenic reactions
      after food intake that could be comparable to allergy, for instance in the
      scriptures of Hippocrates or Lucretius. On this topic we are skeptical, which is
      in agreement with the medical historian Hans Schadewaldt. We also assert that it
      is unlikely that King Richard III was the first food-allergic individual in
      medical literature. Most probably it was not a well-planned poisoning ('allergy')
      with strawberries, but rather a birth defect ('... his harm was ever such since
      his birth') that allowed the Lord Protector to bring Mylord of Ely to the
      scaffold in the Tower, as we can read in The History of King Richard III by
      Thomas More (1478-1535; published by his son-in-law, Rastell, in 1557). In 1912,
      the American pediatrician Oscar Menderson Schloss (1882-1952) was probably the
      first to describe scratch tests in the diagnosis of food allergy. Milestones in
      the practical diagnosis of food allergy are further discussed, including scratch
      tests, intradermal tests, modified prick tests and prick-to-prick tests. False
      negative results can be attributed to the phenomenon of a 'catamnestic reaction'
      according to Max Werner (1911-1987), or to the fermentative degradation of food
      products. Prior to the discovery of immunoglobulin E, which marked a turning
      point in allergy diagnosis, and the introduction of the radioallergosorbent test
      in 1967, several more or less reliable techniques were used in the diagnosis of
      food allergy, such as pulse rate increase after food intake according to Coca,
      the leukopenic index, drop in basophils or drastic platelet decrease. The
      'leukocytotoxic test' (Bryan's test), today called the 'ALCAT' test, shows no
      scientific evidence. The double-blind placebo-controlled food challenge test
      remains the gold standard in the diagnosis of food allergy. For the future,
      component-resolved diagnostics with the use of recombinant molecular allergens or
      chip arrays, such as the ISAC technique, hold a lot of promise. With regard to
      the clinical situation, a subjective selection is given, touching on the pollen
      associated food allergies ('birch-mugwort-celery-spice syndrome'), as well as the
      new phenomenon of lethal food allergies that have appeared since the 1980s.
      Finally, rare ways of elicitation of a 'derivative allergy', first described by
      Erich Fuchs (1921-2008), for example by kissing, as well as 'oral allergy
      syndrome' and oral hyposensitization are considered.

PMID- 24925392
TI  - Drug hypersensitivity.
AB  - Before the arrival of modern pharmacotherapy, drug hypersensitivity reactions
      were virtually unknown. Toxicity from the many plant-, animal- and inorganic
      material-derived remedies must have been much more common. One famous example is
      the intoxications from mercury, which has been used in many ailments, but
      particularly for the treatment of syphilis. It was only in the 19th century when
      more and more active principles from e.g. plants were identified, and when the
      observations of skin reactions became more prevalent. In 1877, Heinrich Kobner
      used for the first time the term 'drug exanthema' (Arznei-Exanthem). Since then,
      many different types of exanthemas from the mild macular-papular forms to the
      severe life-threatening bullous exanthemas such as toxic epidermal necrolysis
      have been observed from numerous drugs. The systematic investigation of severe
      drug reactions has only started in the second half of the 20th century, parallel
      to the increasing knowledge in immunology. Drug hypersensitivity reactions still
      remain one of the most challenging problems in allergology due to their manifold
      clinical manifestations and their very diverse pathophysiology. The introduction
      of new drugs and in turn the emergence of new hypersensitivity reactions will
      remain a challenge in the future.

PMID- 24925393
TI  - Aspirin hypersensitivity.
AB  - Hypersensitivity reactions to acetylsalicylic acid and non-steroidal anti
      inflammatory drugs constitute a major medical concern worldwide. This article
      presents an overview of the observations that led to the discovery of
      cyclooxygenase inhibitors, as a prerequisite to better understand the basic
      concepts supporting seminal investigations carried out in order to elucidate the
      clinical features, pathogenic mechanisms, diagnosis and modern management of
      these common conditions. There are some unmet needs in this clinical area which
      will have to be solved in the future, especially concerning the pathogenesis of
      these reactions and the availability of novel in vitro diagnostic methods sparing
      both patient and physician of the risks inherent to in vivo provocation tests.

PMID- 24925394
TI  - Bradykinin-mediated diseases.
AB  - Diseases which have been demonstrated to be caused by increased plasma levels of
      bradykinin all have angioedema as the common major clinical manifestation.
      Angioedema due to therapy with angiotensin-converting enzyme (ACE) inhibitors is
      caused by suppressed bradykinin degradation so that it accumulates. This occurs
      because ACE metabolizes bradykinin by removal of Phe-Arg from the C-terminus,
      which inactivates it. By contrast, angioedema due to C1 inhibitor deficiency
      (either hereditary types I and II, or acquired) is caused by bradykinin
      overproduction. C1 inhibitor inhibits factor XIIa, kallikrein and activity
      associated with the prekallikrein-HK (high-molecular-weight kininogen) complex.
      In its absence, uncontrolled activation of the plasma bradykinin cascade is seen
      once there has been an initiating stimulus. C4 levels are low in all types of C1
      inhibitor deficiency due to the instability of C1 (C1r, in particular) such that
      some activated C1 always circulates and depletes C4. In the hereditary disorder,
      formation of factor XIIf (factor XII fragment) during attacks of swelling causes
      C4 levels to drop toward zero, and C2 levels decline. A kinin-like molecule, once
      thought to be a cleavage product derived from C2 that contributes to the
      increased vascular permeability seen in hereditary angioedema (HAE), is now
      thought to be an artifact, i.e. no such molecule is demonstrable. The acquired C1
      inhibitor deficiency is associated with clonal disorders of B cell
      hyperreactivity, including lymphoma and monoclonal gammopathy. Most cases have an
      IgG autoantibody to C1 inhibitor which inactivates it so that the presentation is
      strikingly similar to type I HAE. New therapies for types I and II HAE include C1
      inhibitor replacement therapy, ecallantide, a kallikrein antagonist, and
      icatibant, a B2 receptor antagonist. A newly described type III HAE has normal C1
      inhibitor, although it is thought to be mediated by bradykinin, as is an
      antihistamine-resistant subpopulation of patients with 'idiopathic' angioedema.
      The mechanism(s) for the formation of bradykinin in these disorders is unknown.

PMID- 24925395
TI  - The discovery of immunoglobulin e and its role in allergy.
AB  - Immunoglobulin E (IgE) was discovered in 1967. Today, more than 40 years after
      the discovery, the normal beneficial function in the body of this enigmatic
      immunoglobulin still remains unclear. However, ever since the discovery new
      knowledge about allergic diseases and allergens, new treatments and new
      diagnostic tools have continued to emerge as a direct result of our ability to
      identify and measure IgE and IgE antibodies.

PMID- 24925396
TI  - T cell subpopulations.
AB  - The role of allergen-specific CD4+ effector type 2 helper (Th2) cells in the
      pathogenesis of allergic disorders is an established fact. Th2 cells produce
      interleukin (IL)-4 and IL-13, which induce immunoglobulin E production by B
      cells, and IL-5 that allows recruitment of eosinophils. Two main mechanisms
      control the Th2-mediated allergic inflammation: immune deviation (or Th1
      redirection) and immune regulation. Regulatory T (Treg) cells exhibit a CD4+
      phenotype and include Foxp3-positive thymic and induced Tregs, as well as Foxp3
      negative IL-10-producing cells. Both immune deviation and immune regulation
      evoked by the maternal and newborn microbial environment probably operate in
      preventing allergen-specific Th2 responses. However, microbe-related protection
      from allergy seems to mainly depend on epigenetically controlled acetylation of
      the IFNG promoter of CD4+ T cells. Even Th17 and Th9 cells, as well as invariant
      NKT cells, have been implicated in the pathogenesis of allergic disorders, but
      their role is certainly more limited. Recently, innate lymphoid type 2 cells
      (ILC2) have been found to be able to produce high amounts of IL-5 and IL-13 in
      response to stimulation with IL-25 and IL-33 produced by non-immune cells.
      Together with Th2 cells, ILC2 may contribute to the induction and maintenance of
      allergic inflammation.

PMID- 24925397
TI  - Mast cell research.
AB  - The role of mast cells in allergy remained unrevealed until the observation that
      they contained histamine in 1953, and then the discovery of immunoglobulin E
      (IgE) in 1966, nearly a century after Ehrlich's first publication. After the
      discovery of IgE, myeloma-derived IgE from Peter Shackford, who made a great
      contribution to mankind by providing 40 liters of plasma in the year prior to his
      death, was distributed to many researchers. This accelerated the exploration of
      the mechanisms involved in allergic reactions, especially regarding the role of
      mast cells in IgE-mediated reactions. The identification of mast cells as a
      progeny of a bone marrow hematopoietic stem cell in 1977 led us to the successful
      in vitro culture of mast cells. Along with the development of molecular
      biological techniques, the structure of the high-affinity IgE receptor
      (FcepsilonRI) was determined in 1989. Thus, we now understand the whole molecules
      the expression of which is changed when mast cells are activated via FcepsilonRI
      cross-linking. However, the physiological and pathological roles of mast cells,
      especially where IgE is not involved, are not yet fully understood. It will be
      necessary to determine the mechanisms involved in the 'non-IgE-mediated' steps of
      mast cell activation in allergic or other diseases.

PMID- 24925398
TI  - Basophils: historical reflections and perspectives.
AB  - Basophils were discovered by Paul Ehrlich in 1879 and account for less than 1% of
      blood leukocytes, which suggests a tightly controlled regulation of basopoiesis.
      The conservation of basophils in a wide spectrum of the animal kingdom suggests a
      non-redundant role in innate and adaptive immunity. In the early 1990s, it was
      demonstrated that murine and human basophils synthesize interleukin (IL)-4 and IL
      13, thereby suggesting that these cells are important for Th2 polarization and
      IgE synthesis. Human basophils also synthesize IL-3, VEGFs and other pro
      angiogenic molecules. Recently, various groups have introduced the use of
      basophil-depleting antibodies or have developed transgenic mice that
      constitutively lack basophils by more than 90%. These models have highlighted
      previously unrecognized roles of basophils, distinct from those played by mast
      cells, in innate and adaptive immunity. Although the physiologic role of
      basophils remains unknown, there is now compelling evidence that basophils,
      despite their small numbers in peripheral blood and inflamed tissues, are
      critically involved in a wide spectrum of immunologic disorders (allergic,
      autoimmune and infectious diseases, immunodeficiencies and cancer). It is not
      inconceivable that basophils and/or their products could be promising therapeutic
      targets for such disorders.

PMID- 24925399
TI  - Eosinophils.
AB  - In 1846, T. Wharton-Jones described a coarsely granular stage in the development
      of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze
      redefined the coarsely granular cells as a type distinct from finely granular
      cells, rather than just a developmental stage. It was, however, not until 1879,
      when Paul Ehrlich introduced a method to distinguish granular cells by the
      staining properties of their granules, that a classification became possible. An
      intensive staining for eosin, among other aniline dyes, was eponymous for the
      coarsely granular cell type, which thereupon became referred to as eosinophil
      granulocyte. Eosinophilia had already been described in many diseases by the late
      19th century. The role of these cells, however, today remains a matter of
      continuing speculation and investigation. Many functions have been attributed to
      the eosinophil over the years, often linked to increasing knowledge about the
      granular and cytoplasmatic contents. A better understanding of the regulatory
      mechanisms of eosinopoiesis has led to the development of knock-out mice strains
      as well as therapeutic strategies for reducing the eosinophil load in patients.
      The effect of these therapeutics and the characterization of the knock-out
      phenotypes have led to a great increase in the knowledge of the role of the
      eosinophil in disease. Today we think of the eosinophil as a multifunctional cell
      involved in host defense, tissue damage and remodeling, as well as
      immunomodulation.

PMID- 24925400
TI  - The bradykinin-forming cascade: a historical perspective.
AB  - The formation of bradykinin in plasma requires interaction of three proteins,
      namely coagulation factor XII (Hageman factor), prekallikrein and high-molecular
      weight kininogen (HK). Prekallikrein and HK circulate as a bimolecular complex.
      Initiation of the cascade upon binding to negatively charged surfaces (or
      macromolecules) is dependent on factor XII autoactivation, conversion of
      prekallikrein to kallikrein, and a feedback activation of factor XII by
      kallikrein. The latter reaction is extremely rapid relative to factor XII
      autoactivation. The kallikrein then digests HK to liberate bradykinin. The
      natural surface appears to be vascular endothelial cells which express binding
      proteins for factor XII and HK, and activation can proceed along the cell
      surface. Recent findings demonstrate that prekallikrein has enzymatic activity
      separate from that of kallikrein such that it can stoichiometrically bind and
      cleave HK to liberate bradykinin. It is normally prevented from doing so by the
      plasma C1 inhibitor. Release of heat shock protein 90 (HSP-90) from endothelial
      cells can convert prekallikrein to kallikrein (stoichiometrically) within the
      prekallikrein-HK complex, even in the absence of factor XII, and the
      prekallikrein-HK complex can autoactivate to generate kallikrein if phosphate is
      the buffering ion. The effects of phosphate ion and HSP-90 are additive. Thus, an
      active site appears to be induced in prekallikrein by binding to HK and any of
      the aforementioned reactions can generate kallikrein prior to factor XII
      activation by autoactivation of the HK-PK complex. This brief review highlights
      the major discoveries made over the past 50 years which have led to our current
      concepts regarding the constituents and mechanisms of activation of the plasma
      bradykinin-forming cascade.

PMID- 24925401
TI  - Histamine receptors and antihistamines: from discovery to clinical applications.
AB  - The synthesis and the identification of histamine marked a milestone in both
      pharmacological and immunological research. Since Sir Henry Dale and Patrick
      Laidlaw described some of its physiological effects in vivo in 1910, histamine
      has been shown to play a key role in the control of gastric acid secretion and in
      allergic disorders. Using selective agonists and antagonists, as well as
      molecular biology tools, four histamine receptors (H1R, H2R, H3R and H4R) have
      been identified. The Nobel Prize in Physiology and Medicine was awarded to Daniel
      Bovet in 1957 for the discovery of antihistamines (anti-H1R) and to Sir James
      Black in 1988 for the identification of anti-H2R antagonists. Anti-H1R and anti
      H2R histamine receptor antagonists have revolutionized the treatment of certain
      allergic disorders and gastric acid-related conditions, respectively. More
      recently, anti-H3R antagonists have entered early-phase clinical trials for
      possible application in obesity and a variety of neurologic disorders. The
      preferential expression of H4R by several immune cells and its involvement in the
      development of allergic inflammation provide the rationale for the use of anti
      H4R antagonists in allergic and in other immune-related disorders.

PMID- 24925402
TI  - Pollen and pollinosis.
AB  - Pollen grains only represent a small fraction of the total amount of the viable
      biological particles present in the air, but pollen are the most important
      aeroallergens in the outdoor environment. The analysis of pollen has
      traditionally been carried out by microscopy, which can be traced back to the
      17th century. Modern advances in molecular analysis could improve information for
      allergy sufferers and health care professionals. Pollen allergy (pollinosis) was
      first described in the 19th century. The prevalence of respiratory diseases
      increased dramatically during the latter part of the 20th century and millions of
      individuals are now affected. A number of scientists devised equipment to examine
      airborne biological particles during the 19th century, but aerobiological
      monitoring only became standardized during the 20th century. Airborne pollen are
      routinely monitored in many parts of the world, such as North America and Europe,
      and the first limited network has also been created for monitoring airborne
      allergen concentrations. Monitoring of the environment is often based on a
      combination of measurements and model results. Source-based models can increase
      our knowledge of airborne pollen because they can explain situations and
      processes that are almost impossible to understand using observations alone.

PMID- 24925403
TI  - Mites and allergy.
AB  - Allergic diseases triggered by mite allergens include allergic
      rhinoconjunctivitis, asthma, atopic dermatitis and other skin diseases. Since the
      early discovery of the allergenic role of mites of the genus Dermatophagoides in
      the mid 1960s, numerous species have been described as the source of allergens
      capable of sensitizing and inducing allergic symptoms in sensitized and
      genetically predisposed individuals. The main sources of allergens in house dust
      worldwide are the fecal pellets of the mite species D. pteronyssinus, D. farinae,
      Euroglyphus maynei and the storage mites Blomia tropicalis, Lepidoglyphus
      destructor and Tyropahgus putrescentiae. Group 1 and 2 allergens are major house
      dust mite allergens. The main allergens in storage mites include fatty acid
      binding proteins, tropomyosin and paramyosin homologues, apolipophorin-like
      proteins, alpha-tubulins and others, such as group 2, 5 and 7 allergens. Cross
      reactivity is an important and common immunological feature among mites.
      Currently, purified native or recombinant allergens, epitope mapping, proteomic
      approaches and T cell proliferation techniques are being used to assess cross
      reactivity. Mites contain potent enzymes capable of degrading a wide range of
      substrates. Most mite allergens are enzymes. Advances in genomics and molecular
      biology will improve our ability to understand the genetics of specific IgE
      responses to mites. Mite allergen avoidance and immunotherapy are the only two
      allergen-specific ways to treat mite-induced respiratory and cutaneous diseases.

PMID- 24925404
TI  - Mammalian airborne allergens.
AB  - Historically, horse dandruff was a favorite allergen source material. Today,
      however, allergic symptoms due to airborne mammalian allergens are mostly a
      result of indoor exposure, be it at home, at work or even at school. The
      relevance of mammalian allergens in relation to the allergenic activity of house
      dust extract is briefly discussed in the historical context of two other proposed
      sources of house dust allergenic activity: mites and Maillard-type lysine-sugar
      conjugates. Mammalian proteins involved in allergic reactions to airborne dust
      are largely found in only 2 protein families: lipocalins and secretoglobins (Fel
      d 1-like proteins), with a relatively minor contribution of serum albumins,
      cystatins and latherins. Both the lipocalin and the secretoglobin family are very
      complex. In some instances this results in a blurred separation between important
      and less important allergenic family members. The past 50 years have provided us
      with much detailed information on the genomic organization and protein structure
      of many of these allergens. However, the complex family relations, combined with
      the wide range of post-translational enzymatic and non-enzymatic modifications,
      make a proper qualitative and quantitative description of the important mammalian
      indoor airborne allergens still a significant proteomic challenge.

PMID- 24925405
TI  - The latex story.
AB  - The milky sap of the rubber tree Hevea brasiliensis is the source of the
      commercial production of natural rubber latex (NRL) devices, and also represents
      a source of potent allergenic proteins. NRL materials were introduced in the
      health care field in about 1840 with the advent of technical abilities to produce
      suitable and flexible NRL materials for medical products, especially gloves. In
      the late 1980s, with the increase of transmittable diseases, particularly HIV
      infection, the use of NRL gloves increased dramatically. During the 1990s, NRL
      emerged as a major cause of clinically relevant allergy in health care workers
      using NRL gloves and spina bifida patients with operation on the first day. The
      increased recognition of NRL allergies, the enhanced research on allergen
      characterization and sensitization mechanisms, and education about this allergy
      in health care facilities combined with the introduction of powder-free gloves
      with reduced protein levels are all factors associated with a decline in the
      number of suspected cases of NRL allergies in the late 1990s. NRL allergy is a
      very good example of a 'new allergy' that suddenly arises with tremendous health
      and economic implications, and also of an allergy which becomes history in a
      relatively short period of time based on successful primary prevention strategies
      by strict allergen avoidance.

PMID- 24925406
TI  - Peanut allergens.
AB  - The earliest known evidence of peanut farming dates back 7,600 years. With a
      prevalence of roughly 1%, peanut allergy is a diagnostic and treatment challenge,
      but is also a very good model for studying all aspects of food allergy, including
      its molecular basis and pathomechanisms. Therefore, the very starting point for
      elucidating all these aspects is the identification of peanut allergens with
      subsequent clearing of their structure and their preparation as pure recombinant
      and/or natural allergens. This is the basis for in vitro diagnostic tests as well
      as the development of immunotherapeutic drugs. With regard to class I food
      allergy, peanut allergy affects by far the largest group of patients. In peanuts,
      12 allergens have been identified and their molecular characteristics are
      described herein. Ara h 1, Ara h 3.01 and Ara h 3.02 (the former Ara h 4) belong
      to the cupin superfamily. The conglutins Ara h 2, Ara h 6 and Ara h 7, and the
      non-specific lipid transfer protein Ara h 9 belong to the prolamin superfamily.
      Ara h 5 (profilin) and Ara h 8 (Bet v 1-homologous protein) cause class II food
      allergies and are associated with inhalation allergy to pollen via the sequential
      and/or conformational similarity of molecules. Two peanut oleosins are listed as
      Ara h 10 and Ara h 11 and two defensins as Ara h 12 and Ara h 13 by the WHO/IUIS
      Allergen Nomenclature Subcommittee. The effect of the above-specified allergens
      has to be considered in the context of their matrix, which is influenced by
      processing factors and the individual's immune system.

PMID- 24925407
TI  - Environmental pollution and allergy: historical aspects.
AB  - It may be a coincidence, but it is a fact that the first clear characterization
      of hay fever began in England where modern industrialization started in Europe.
      Only at the end of the 20th century were associations of the increasing
      prevalence of allergy with outdoor air pollution discussed. The seminal study
      came from Japan from the group of T. Miyamoto linking the increase in Japanese
      cedar pollinosis to an increased prevalence of Diesel cars and probably exposure
      to Diesel exhaust in epidemiological, animal experimental and in vitro studies.
      In Germany first epidemiological studies were done in North Rhine-Westphalia and
      Bavaria in 1987 and 1988 showing a striking prevalence of allergic disease of up
      to 10-20% in preschool children. After German reunification the most surprising
      observation was a lower prevalence of hay fever in East German children compared
      to the West, although there was a much higher air pollution with SO2 and large
      particulate matter. Modern smog as found over West German cities most likely
      originating from traffic exhaust and consisting of fine and ultrafine particles
      was shown to be associated with higher incidence rates of allergy and allergic
      sensitization. In the 10 years after reunification there was a steep increase of
      allergy prevalence in East German children reaching almost the same level as in
      West Germany. Obviously, a multitude of lifestyle factors - beyond air pollution 
      may be involved in the explanation of this phenomenon. Surprisingly the skin
      manifestation of atopy, namely atopic eczema, was more frequent in East German
      children compared to the West, thus differing from airway allergy. Meanwhile in
      vitro studies and animal experiments have shown that a variety of air pollutants
      mostly from environmental tobacco smoke (indoors) and from traffic exhaust
      (outdoors) can stimulate immune cells inducing a Th2-dominated response besides
      their irritative effects. While 50 years ago in allergy textbooks a clear
      distinction was made between 'toxic' or 'allergic', the newly developed concept
      of allergotoxicology has stimulated research tremendously, meaning 'the
      investigation of effects of toxic substances upon the induction, elicitation and
      maintenance of allergic reactions'.

PMID- 24925408
TI  - Farmers and their environment: protective influences of the farming environment
      against the development of allergies.
AB  - Compared with other population groups, the way of life of farmers can be viewed
      as being similar to that of our ancestors. The settled continuation of
      generations within certain critical geographical and environmental conditions
      requires a special local network of knowledge and experience. The immune system
      provides protection against microbes and their toxins. Each strong reaction
      impedes an active adaptation. Allergy is therefore a harmful intolerance and
      represents one of many different paradoxes. The aim of this chapter is to
      demonstrate some of the interactions of tolerance and adaptation from a
      historical background.

PMID- 24925409
TI  - History of catecholamine research.
AB  - The prominence of catecholamines and their congeners in allergic diseases rests
      chiefly on their use in asthma and acute hypersensitivity reactions, such as
      anaphylaxis. They act in these indications by activating both alpha- and beta
      adrenoceptors. Adrenaline, the prototype, was discovered in the adrenals in
      1893/1894. In 1939, dopa decarboxylase was the first enzyme in the biosynthesis
      of catecholamines to be described. Later other catecholamines like noradrenaline
      and dopamine were characterized. The identification of the active chemicals went
      along with studies regarding catecholamine receptors. It took until 1948 before
      the existence of at least two different receptors for the different effects was
      accepted. Meanwhile, genes from all mammalian catecholamine receptors have been
      cloned.

PMID- 24925410
TI  - Antihistamines.
AB  - The discovery of histamine, its physiological role and reversal of its
      pharmacological effects by antihistamines takes us on a journey through the
      origins of modern physiology and the rising understanding of pharmacology at the
      end of the 19th and the early part of the 20th centuries. This journey, which has
      been traced in the excellent historical review by Michael Emanuel [Clin Exp
      Allergy 1999;29:1-11], is populated by some of the greatest scientists of the
      era, including six Nobel laureates - Bovet, Dale, Ehrlich, Richet, Windaus and
      Black. In addition, it laid the basis of medicinal chemistry not only for
      antihistamines, but also for the discovery of a plethora of drugs still in use
      today.

PMID- 24925411
TI  - Glucocorticoids.
AB  - Glucocorticoids are the most effective anti-inflammatory treatment for allergic
      diseases, and inhaled glucocorticoids have now become the first-line treatment
      for asthma. Glucocorticoids were discovered in the 1940s as extracts of the
      adrenal cortex and this was followed by the isolation of adrenocorticotropic
      hormone (ACTH) from pituitary gland extracts. Cortisone and ACTH were found to be
      very beneficial in the treatment of rheumatoid arthritis and Kendall, Reichstein
      and Hench received the Nobel Prize in Physiology and Medicine for this work in
      1950. Bordley and colleagues first showed that ACTH was very beneficial in the
      treatment of allergic diseases in 1949, but the use of systemic glucocorticoids
      was limited by side effects. Inhaled glucocorticoids were discovered from topical
      steroids developed for skin inflammation and beclomethasone dipropionate was
      introduced in 1972, initially in low doses but later in higher doses, and became
      the standard treatment for persistent asthma. Subsequently, inhaled
      glucocorticoids were combined with long-acting beta2-agonists in combination
      inhalers for even greater therapeutic benefit. There is now a good understanding
      of the molecular basis for the anti-inflammatory effects of glucocorticoids in
      allergic diseases. The search for even safer glucocorticoids based on the
      dissociation of anti-inflammatory and side effect mechanisms is currently
      ongoing.

PMID- 24925412
TI  - Chromones.
AB  - The chromones are a class of chemical compounds characterised by the presence of
      the structure 5:6 benz-1:4-pyrone in their chemical make-up. The first chromone
      in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga,
      and had been used for centuries as a diuretic and as a smooth muscle relaxant.
      Its use in bronchial asthma was reported in 1947. In the 1950s, Benger's
      Laboratories embarked on a research programme to synthesise and develop
      modifications of khellin for the treatment of asthma. New compounds were screened
      using animal models to test the ability of the compound to prevent the
      anaphylactic release of histamine and SRS-A (leukotrienes) from sensitised guinea
      pig lung, and a human model to check the ability to reduce the
      bronchoconstriction induced by inhaled antigen bronchial challenge. For initial
      screening the human work was undertaken by Dr. R.E.C. Altounyan, who suffered
      from allergic bronchial asthma and was employed by Benger's Laboratories. After 8
      years and more than 600 challenges using over 200 compounds, in 1965 Altounyan
      arrived at disodium cromoglycate (DSCG), the chromone that met the criteria of
      providing more than 6 h of protection. DSCG is still used today as a mast cell
      stabiliser.

PMID- 24925413
TI  - Characterization and standardization of allergen extracts.
AB  - This paper summarizes the development of the extraction and characterization of
      allergens responsible for the induction of immunoglobulin (lg) E-induced
      allergies from the beginning of the 20th century, including the nomenclature of
      allergens. The majority of papers characterizing allergens and allergen extracts
      state that the lack of standardization of allergen extracts is the reason for the
      paper, and so it has been for more than 100 years. A natural part of that process
      might be the isolation of an allergen molecule and this starts the speculation of
      'what makes that allergen an allergen?' To achieve the perfect standardization is
      a desirable end that is still awaited. So far none of these problems have been
      finally solved. I started in allergy shortly after the discovery of IgE in 1967.
      Since that time the history as I remember it is based on the literature, my
      interpretation of it, and of course may be a little biased due to personal
      prejudice! The history of the last 10-15 years has still not matured and it might
      be a little early to draw conclusions. However, at the end of this chapter I do
      dare to make a few conclusions after having followed the development in this
      field for 40 years. As this is history it is not meant to be either comprehensive
      or technically and scientifically precise in all aspects, but rather draws on
      some thoughts as to what in my mind have been important developments until now.
      Specific techniques are only mentioned by name and not intended to be discussed
      in depth. This activity has, however, pushed me to reflect on my hopes and
      speculations at the time of my introduction to the field of allergen chemistry.
      To my surprise I realize that far more than I ever expected at that time has been
      fulfilled. It has been extremely exciting to be a part of that development.

PMID- 24925414
TI  - Allergen-specific immunotherapy.
AB  - Specific immunotherapy was introduced for the treatment of grass pollen-induced
      hay fever in 1911. The treatment was soon extended to other pollens as well as
      perennial allergens, and to the treatment of bronchial asthma. Definitive studies
      of its efficacy for both rhinitis and asthma came only many decades later.
      Understanding gradually emerged of the underlying immunologic mechanisms that
      include the generation of regulatory T lymphocytes, immune deviation from
      allergen-specific Th2 to Th1 responses, and a shift in allergen-specific antibody
      production from immunoglobulin (Ig) E to IgG4. Along with understanding of the
      immune basis came an appreciation that immunotherapy modifies allergic disease
      expression, producing protection against disease progression and symptomatic
      improvement that persists for years after the treatment is discontinued. Recent
      new directions for immunotherapy include sublingual administration of inhalant
      allergens and use of the oral route to treat food allergy.

PMID- 24925415
TI  - K. Frank Austen. Boston, Mass., USA.

PMID- 24925416
TI  - John Bienenstock. Hamilton, Ont., Canada.

PMID- 24925417
TI  - Kurt Blaser. Davos, Switzerland.

PMID- 24925418
TI  - Alain de Weck (1928-2013). Fribourg, Switzerland.

PMID- 24925419
TI  - Alfred William Frankland. London, UK.

PMID- 24925420
TI  - OSCAR L. Frick. San francisco, Calif., USA.

PMID- 24925421
TI  - Kimishige Ishizaka. Tokyo, Japan.

PMID- 24925422
TI  - Lothar Jager. Jena, Germany.

PMID- 24925423
TI  - Terumasa Miyamoto. Tokyo, Japan.

PMID- 24925424
TI  - Harry Morrow Brown (1917-2013). Derby, UK.

PMID- 24925425
TI  - Albert K. Oehling. Navaleno, Spain.

PMID- 24925426
TI  - Heimo Reulecke. Iffeldorf, Germany.

PMID- 24925427
TI  - Vaclav Spicak. Prague, Czech Republic.

PMID- 24925440
TI  - Effects of multiple doses of voriconazole on the vision of healthy volunteers: a
      double-blind, placebo-controlled study.
AB  - PURPOSE: To investigate the effects, and their reversibility, of multiple oral
      voriconazole doses on a variety of visual tests in healthy male volunteers.
      METHODS: Single-center, double-blind, randomized, placebo-controlled, parallel
      group study in 36 volunteers who received voriconazole (n=18, 400 mg every 12 h
      on day 1, then 300 mg every 12 h for 27.5 days) or matched placebo (n=18).
      Electroretinograms (ERGs) and ophthalmological examinations were performed at
      screening, throughout the study and at follow-up. RESULTS: Fifteen (83.3%)
      volunteers treated with voriconazole experienced >=1 treatment-related visual
      adverse events (AEs); these included enhanced visual perceptions, blurred vision,
      color vision changes and photophobia. No serious AEs were reported. Voriconazole
      reduced from baseline scotopic maximal a- and b-wave amplitude, shortened
      implicit time and decreased oscillatory potential amplitude compared with
      placebo. Under photopic conditions, the 30-Hz flicker response amplitude was
      significantly reduced and was accompanied by a slight but nonsignificant
      prolongation of peak time. These effects did not progress in degree over the
      treatment period, and mean changes from baseline in ERG parameters were similar
      to placebo by day 43 (14 days after end of treatment). In the first week, color
      vision discrimination was impaired in the tritan axis, although this resolved by
      end of treatment and was similar to placebo by day 43. Mean deviation in the
      static visual field indicated increased sensitivity following voriconazole
      treatment, correlating with decreased amplitude in conjunction with shortened
      implicit time. CONCLUSIONS: Effects of voriconazole on altered visual perception,
      ERG, color vision and static visual field thresholds are nonprogressive over a
      treatment period and reversible. It is hypothesized that voriconazole has a
      pharmacological effect on rod and cone pathways including a possible mechanism of
      disinhibition that reversibly puts the retina in a more light-adapted state and
      leads to increased relative contrast sensitivity.

PMID- 24925441
TI  - MR diffusion tensor imaging of normal kidneys.
AB  - PURPOSE: To assess the feasibility of diffusion tensor imaging (DTI) of normal
      kidneys and the influence of hydration state. MATERIALS AND METHODS: Ten healthy
      volunteers underwent renal DTI after fasting for 12 hours and 4 hours, without
      fasting, and following water diuresis. Medullary and cortical apparent diffusion
      coefficient (ADC) and fractional anisotropy (FA) values were measured and
      compared in the four different states of hydration. DTI was performed with a 3T
      magnetic resonance imaging (MRI) system using fat-saturated single-shot spin-echo
      echo planar imaging sequence. RESULTS: ADC of normal cortex (2.387 +/- 0.081 *
      10(-3) mm(2) /s) was significantly higher (t = 20.126, P = 0) than that of
      medulla (1.990 +/- 0.063 * 10(-3) mm(2) /s). The FA value of normal cortex (0.282
      +/- 0.017) was significantly lower (t = -42.713, P = 0) than that of medulla
      (0.447 +/- 0.022). The ADC and FA values of the left renal cortex (2.404 +/-
      0.082 * 10(-3) mm(2) /s, 0.282 +/- 0.017) and medulla (2.002 +/- 0.081 * 10(-3)
      mm(2) /s, 0.452 +/- 0.024) were not significantly different (P > 0.05) from those
      of right renal cortex (2.369 +/- 0.080 * 10(-3) mm(2) /s, 0.283 +/- 0.018) and
      medulla (1.978 +/- 0.039 * 10(-3) mm(2) /s, 0.443 +/- 0.019). Values for ADC
      (*10(-3) mm(2) /s) and FA in the 12-hour fasting, 4-hour fasting, nonfasting, and
      water diuresis states were 2.372 +/- 0.095 and 0.278 +/- 0.018, 2.387 +/- 0.081
      and 0.282 +/- 0.017, 2.416 +/- 0.051 and 0.279 +/- 0.023, 2.421 +/- 0.068, and
      0.270 +/- 0.021, respectively, in cortex, 1.972 +/- 0.084 and 0.438 +/- 0.014,
      1.990 +/- 0.063 and 0.447 +/- 0.022, 2.021 +/- 0.081 and 0.450 +/- 0.031, 2.016
      +/- 0.076 and 0.449 +/- 0.028, respectively, in medulla. The ADC and FA values in
      different hydration states were not significantly different (P > 0.05).
      CONCLUSION: DTI of normal kidneys is feasible with reproducible ADC and FA values
      independent of hydration states.

PMID- 24925442
TI  - Understanding the cancer pain experience.
AB  - Cancer pain management is a major element of successful cancer survivorship.
      Regardless of where someone is along the cancer experience, from a newly
      diagnosed patient to long-term survivor, pain is a potential treatment-related
      effect that can have a significant impact on a survivor's life. Quality pain
      management for cancer survivors is complicated by the fact that cancer-related
      pain can be due to the tumor, surgery, radiation, and/or chemotherapy.
      Additionally, the pain experience is related to many psychosocial/spiritual
      factors. Despite almost 40 years of attention devoted to improving cancer pain
      management, many cancer survivors are less than optimally treated, often owing to
      survivor and healthcare provider knowledge barriers. This article reviews some of
      the latest research related to cancer pain management treatment options,
      measurement/assessment, and interventions. Progress has been made in
      understanding new aspects of the pain experience, but more work is yet to be
      done. 

PMID- 24925443
TI  - Impaired cardiac anti-oxidant activity in diabetes: human and correlative
      experimental studies.
AB  - Increased reactive oxygen species (ROS) are traditionally viewed as arising from
      the metabolic flux of diabetes, although reduction in the activity of anti
      oxidant systems has also been implicated. Among the latter is the major thiol
      reducing thioredoxin system, the activity of which may be diminished by high
      glucose-induced expression of its endogenous inhibitor, thioredoxin interacting
      protein (TxnIP). We assessed TxnIP mRNA/protein expression along with thioredoxin
      activity in human right atrial biopsy specimens from subjects with and without
      diabetes undergoing coronary artery grafting. In correlative experimental
      studies, we examined TxnIP expression in both type 1 and type 2 rodent models of
      diabetic cardiomyopathy. Finally, we used in vitro gene silencing to determine
      the contribution of changes in TxnIP abundance to the high glucose-induced
      reduction in thioredoxin activity. In human right atrial biopsies, diabetes was
      associated with a >30-fold increase in TxnIP gene expression and a 17 % increase
      in TxnIP protein expression (both p < 0.05). This was associated with a 21 %
      reduction in thioredoxin activity when compared to human non-diabetic cardiac
      biopsy samples (all p < 0.05). In correlative animal studies, both type 1 and
      type 2 diabetic rats demonstrated a significant increase in TxnIP mRNA and
      reduction in thioredoxin activity when compared to non-diabetic animals (all p <
      0.05). This was associated with a significant increase in ROS (p < 0.05 when
      compared with control). In cultured cardiac myocytes, high glucose increased ROS
      and TxnIP mRNA expression, in association with a reduction in thioredoxin
      activity (p < 0.01). These findings were abrogated by TxnIP small interfering RNA
      (siRNA). Scrambled siRNA had no effect upon ROS or TxnIP expression. High glucose
      reduces thioredoxin activity and increases ROS via TxnIP overexpression. These
      findings suggest that impaired thiol reductive capacity, through altered TxnIP
      expression, contributes to increased ROS in the diabetic heart. 

PMID- 24925444
TI  - Three-dimensional analysis of subchondral cysts in hip osteoarthritis: an ex vivo
      HR-pQCT study.
AB  - INTRODUCTION: Subchondral cysts are deeply related to the pathogenesis of
      osteoarthritis (OA), but the factors contributing to cyst formation are not well
      known. A three-dimensional analysis of subchondral cysts at the micro-structural
      level was conducted using a high-resolution peripheral quantitative CT (HR-pQCT),
      and their relationships with cartilage attrition and subchondral bone
      microstructure were investigated. METHODS: Femoral heads extracted from ten
      female patients with hip OA were scanned using an HR-pQCT at a voxel size of
      41MUm. The volume fractions, numbers, and sizes of the cysts were measured in the
      subchondral bone region under the area of cartilage loss. Furthermore, the areas
      of cartilage loss, as well as the microstructure of the subchondral bones, were
      also measured, and their correlations with the cysts were analyzed. RESULTS: The
      volume fractions of cysts within subchondral bone regions varied from 2% to 33%,
      the numbers of cysts varied from 6 to 87, and the sizes varied from 1mm(3) to
      657mm(3). There was a positive correlation between the number of cysts and bone
      volume (r>0.8, p<0.01). CONCLUSION: The degree of cyst formation showed a wide
      distribution in number and volume, and there was a close relationship between
      multiple cyst formation and bone sclerosis, which might be caused by reactive
      bone formation that occurred around each cyst.

PMID- 24925445
TI  - Characterization of cancellous and cortical bone strain in the in vivo mouse
      tibial loading model using microCT-based finite element analysis.
AB  - The in vivo mouse tibial loading model has been increasingly used to understand
      the mechanisms governing the mechanobiological responses of cancellous and
      cortical bone tissues to physical stimuli. Accurate characterization of the
      strain environment throughout the tibia is fundamental in relating localized
      mechanobiological processes to specific strain stimuli in the skeleton. MicroCT
      based finite element analysis, together with diaphyseal strain gauge measures,
      was conducted to quantify the strain field in the tibiae of 16-wk-old female
      C57Bl/6 mice during in vivo dynamic compressive loading. Despite a strong
      correlation between the experimentally-measured and computationally-modeled
      strains at the gauge site, no correlations existed between the strain at the
      gauge site and the peak strains in the proximal cancellous and midshaft cortical
      bone, indicating the limitations of using a single diaphyseal strain gauge to
      estimate strain in the entire tibia. The peak compressive and tensile principal
      strain magnitudes in the proximal cancellous bone were 10% and 34% lower than
      those in the midshaft cortical bone. Sensitivity analyses showed that modeling
      bone tissue as a heterogeneous material had a strong effect on cancellous strain
      characterization while cortical strain and whole-bone stiffness were primarily
      affected by the presence of the fibula and the proximal boundary conditions.
      These results show that microCT-based finite element analysis combined with
      strain gauge measures provides detailed resolution of the tissue-level strain in
      both the cancellous and cortical bones of the mouse tibia during in vivo
      compression loading, which is necessary for interpreting localized patterns of
      modeling/remodeling and, potentially, gene and protein expression in skeletal
      mechanobiology studies. 

PMID- 24925446
TI  - A Drosophila laboratory evolution experiment points to low evolutionary potential
      under increased temperatures likely to be experienced in the future.
AB  - The ability to respond evolutionarily to increasing temperatures is important for
      survival of ectotherms in a changing climate. Recent studies suggest that upper
      thermal limits may be evolutionary constrained. We address this hypothesis in a
      laboratory evolution experiment, encompassing ecologically relevant thermal
      regimes. To examine the potential for species to respond to climate change, we
      exposed replicate populations of Drosophila melanogaster to increasing
      temperatures (0.3  degrees C every generation) for 20 generations, whereas
      corresponding replicate control populations were held at benign thermal
      conditions throughout the experiment. We hypothesized that replicate populations
      exposed to increasing temperatures would show increased resistance to warm and
      dry environments compared with replicate control populations. Contrasting
      replicate populations held at the two thermal regimes showed (i) an increase in
      desiccation resistance and a decline in heat knock-down resistance in replicate
      populations exposed to increasing temperatures, (ii) similar egg-to-adult
      viability and fecundity in replicate populations from the two thermal regimes,
      when assessed at high stressful temperatures and (iii) no difference in
      nucleotide diversity between thermal regimes. The limited scope for adaptive
      evolutionary responses shown in this study highlights the challenges faced by
      ectotherms under climate change.

PMID- 24925447
TI  - Derivation of uncertainty functions from validation studies in biological fluids:
      application to the analysis of caffeine and its major metabolites in human plasma
      samples.
AB  - Procedures for estimating the measurement uncertainty (MU) of the concentration
      of a given analyte in a sample are of major concern for analytical chemists.
      Unfortunately, it is still unclear how and why MU should be assessed. While
      several possibilities exist, an appropriate approach consists in using method
      validation data for the evaluation of MU. This was demonstrated by a validation
      study achieved in the framework of a clinical study related to caffeine in sports
      medicine, where the results were used for the evaluation of MU. After validation
      of the method developed using ultra-high pressure liquid chromatography-mass
      spectrometry for caffeine and its three main metabolites, accuracy profiles were
      built for each analyte. The first important conclusion is that the developed
      method was valid for all compounds and met the given specifications for the
      application (fit for purpose). Relevant estimates of combined standard
      uncertainty were computed to obtain uncertainty functions, which allow obtaining
      values of MU as a function of the concentration of the analyte. The great
      advantage of both uncertainty function and uncertainty profile is the development
      of a continuous model that enables easy calculation of the standard, expanded and
      relative expanded uncertainty at any concentration within the validation domain.
      In fact, the expanded uncertainty interval is assumed to contain 95% of all
      possible measurements, regardless of the concentration. Finally, the uncertainty
      function enables the determination of the lowest limit of quantification by
      selecting adequate acceptance limits, with the limit of quantification being
      defined as the point where the relative uncertainty equals the acceptance limit
      threshold. It has to be noted that further discussions remain mandatory to
      establish which criteria should be applied to define an adequate decision
      threshold, and the proposal afforded in this work may open new avenues in this
      direction. 

PMID- 24925448
TI  - Enthalpy contributions to adsorption of highly charged lysozyme onto a cation
      exchanger under linear and overloaded conditions.
AB  - An investigation of the adsorption mechanism of lysozyme onto carboxymethyl
      cellulose (CMC) was conducted using flow calorimetry and adsorption isotherm
      measurements. This study was undertaken to provide additional insight into the
      underlying mechanisms involved in protein adsorption that traditional approaches
      such isotherm measurements or van't Hoff analysis can't always provide,
      particularly when protein adsorption occurs under overloaded conditions. Lysozyme
      and CMC were selected for this study because the characteristics of the protein
      and the adsorbent are well known, hence, allowing the focus of this work to be on
      the driving forces influencing adsorption. Calorimetry results have showed that
      lysozyme adsorption onto CMC produced both exothermic and endothermic heats of
      adsorption. More specifically flow calorimetry data coupled with peak
      deconvolution methods illustrated a series of chronological events that included
      dilution, primary protein adsorption, rearrangement of surface proteins and a
      secondary adsorption of lysozyme molecules. The observations and conclusions
      derived from the experimental work presented in our figures and tables were
      developed within the mechanistic framework proposed by Lin et al., J. Chromatogr.
      A. 912 (2001) 281. 

PMID- 24925449
TI  - Effect of the pressure on pre-column sample dispersion theory, experiments, and
      practical consequences.
AB  - The effect of the pressure on the dispersion of a low molecular weight compound
      along 0.508 and 1.016 mm i.d. * 50 cm long open circular tubes was investigated
      theoretically and experimentally. The theoretical predictions were based on the
      early models of dispersion derived by Aris and Taylor (1953) and on the
      approximate model of Alizadeh for the time moments (1980). Experimentally, the
      system pressure was increased at constant flow rate (0.15 mL/min) from less than
      20 to nearly 1,000 bar by using a series of capillary tubes (25 MUm i.d. PEEKSIL
      tubes) of increasing flow resistances placed upstream the detection cell of a
      commercial very high pressure liquid chromatograph (vHPLC) but downstream the 50
      cm long tube. Theoretical and experimental results agree that the peak variance
      increases linearly with increasing pressure in the tube volume. The relative
      increase of the peak variance is 7% above that measured at low pressure (<20 bar)
      for each 100 bar increment in the tube volume. This result confirms that accurate
      measurements of the column efficiency corrected for extra-column contribution
      cannot be made by replacing the column with a zero dead volume union connector,
      because the pressures applied in the pre-column volume are significantly
      different in these two cases. This work shows also that increasing the pressure
      in the pre-column volume by increasing the flow rate affects the apparent column
      efficiency that is measured, independently of the direct effect of the flow rate.
      For a 2.1 * 50mm column packed with 1.3 MUm core-shell particles run with a
      classic Acquity system, the associated relative decreases of the column
      efficiency are expected to be -30%, -20%, and -5% for retention factors of 1, 3,
      and 10, respectively. The column HETP is no longer independent of its length.

PMID- 24925450
TI  - Ionic liquid-based electromembrane extraction and its comparison with traditional
      organic solvent based electromembrane extraction for the determination of
      strychnine and brucine in human urine.
AB  - An ionic liquid-based electromembrane extraction (IL-EME) method was presented,
      and its performance was compared with 2-ethylnitrobenzene (ENB) based EME for the
      determination of strychnine and brucine in human urine. For the two methods, the
      fundamental extraction parameters such as supported liquid membrane, voltage,
      extraction time, pH values of sample solution and acceptor solution, temperature
      and salting-out effect were separately optimized. IL-EME provided 96- and 122
      fold enrichment factors for strychnine and brucine, respectively, which were
      better than those obtained in EME (83- and 86-fold, respectively). The
      calibration curves were linear over the ranges of 20-720 MUg L(-1) for strychnine
      and 20-640 MUg L(-1) for brucine with the correlation coefficients higher than
      0.9950. The repeatability of EME and IL-EME were evaluated by five parallel
      experiments giving the relative standard deviations of 5.12-6.98%. As the results
      indicated, compared with ENB based EME, the proposed IL-EME is more reliable and
      could provide better extraction performance for the determination of strychnine
      and brucine in human urine.

PMID- 24925451
TI  - Sensitive, accurate and rapid detection of trace aliphatic amines in
      environmental samples with ultrasonic-assisted derivatization microextraction
      using a new fluorescent reagent for high performance liquid chromatography.
AB  - A new fluorescent reagent, 1-(1H-imidazol-1-yl)-2-(2-phenyl-1H-phenanthro[9,10
      d]imidazol-1-yl)ethanone (IPPIE), is synthesized, and a simple pretreatment based
      on ultrasonic-assisted derivatization microextraction (UDME) with IPPIE is
      proposed for the selective derivatization of 12 aliphatic amines (C1: methylamine
      C12: dodecylamine) in complex matrix samples (irrigation water, river water,
      waste water, cultivated soil, riverbank soil and riverbed soil). Under the
      optimal experimental conditions (solvent: ACN-HCl, catalyst: none, molar ratio:
      4.3, time: 8 min and temperature: 80 degrees C), micro amount of sample (40 MUL;
      5mg) can be pretreated in only 10 min, with no preconcentration, evaporation or
      other additional manual operations required. The interfering substances (aromatic
      amines, aliphatic alcohols and phenols) get the derivatization yields of <5%,
      causing insignificant matrix effects (<4%). IPPIE-analyte derivatives are
      separated by high performance liquid chromatography (HPLC) and quantified by
      fluorescence detection (FD). The very low instrumental detection limits (IDL:
      0.66-4.02 ng/L) and method detection limits (MDL: 0.04-0.33 ng/g; 5.96-45.61
      ng/L) are achieved. Analytes are further identified from adjacent peaks by on
      line ion trap mass spectrometry (MS), thereby avoiding additional operations for
      impurities. With this UDME-HPLC-FD-MS method, the accuracy (-0.73-2.12%),
      precision (intra-day: 0.87-3.39%; inter-day: 0.16-4.12%), recovery (97.01
      104.10%) and sensitivity were significantly improved. Successful applications in
      environmental samples demonstrate the superiority of this method in the
      sensitive, accurate and rapid determination of trace aliphatic amines in micro
      amount of complex samples.

PMID- 24925452
TI  - Application of cyclodextrin-based eluents in hydrophobic charge-induction
      chromatography: elution of antibody at neutral pH.
AB  - Hydrophobic charge-induction chromatography (HCIC) has emerged as a useful
      addition to Protein A chromatography for antibody purification due to its
      remarkable merits in cost and stability. However, the instability of antibody
      during acidic elution, which may cause inactivation and aggregation, is still a
      major concern for the efficiency of this method. The aim of this study is to
      develop a new strategy of competitive elution with inclusion complexes in HCIC,
      and to apply it to antibody elution under neutral pH conditions. Interactions
      between 4-mercaptoethylpyridine (MEP), a typical ligand of HCIC, and four
      different types of cyclodextrins (CDs) were investigated by molecular docking;
      immunoglobulin G (IgG) elution capacities of CDs were characterized on MEP-based
      HCIC mediums. The results demonstrated the general effectiveness of CD-based
      eluents for HCIC. This type of displacement eluents could allow an efficient
      elution of bound antibody over a broad range of pH and ion strength. With 15 mM
      beta-CD, elution of human IgG was achieved at physiological pH, with an average
      IgG recovery of 87%. When this elution strategy was used to separate antibody
      directly from human serum, substantial elution of bound IgG could be obtained at
      pH 7.4, with product purity comparable to traditional method with an acidic
      buffer. We expect such method can be of special interest in developing HCIC
      elution strategy for the proteins like antibody that are sensitive to acidic
      conditions.

PMID- 24925453
TI  - Determination of benzodiazepines, related pharmaceuticals and metabolites in
      water by solid-phase extraction and liquid-chromatography-tandem mass
      spectrometry.
AB  - This work presents a method for the simultaneous determination of 23
      benzodiazepines, metabolites and related pharmaceuticals (zolpidem,
      methylphenidate and ritalinic acid) by solid-phase extraction (SPE) followed by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). Different SPE
      cartridges were considered: hydrophilic modified reversed-phase (Oasis HLB) and
      their modified versions containing also a cationic-exchange group (Oasis MCX) or
      anionic-exchange (Oasis MAX) funcionalities. Stability of analytes and the impact
      of the final eluate volume on the matrix effects on LC-MS/MS were also
      considered. In the final method, 100-200 mL of sample are extracted with Oasis
      MCX (60 mg), eluted with 5 mL of methanol (1.25% NH3) and the eluate concentrated
      and analyzed by LC-MS/MS. Under these conditions, LOQs were established between
      0.1 and 18 ng L(-1) for influent wastewater. The use of surrogated deuterated
      internal standards allows obtaining recoveries in the 84-122% range. Finally the
      method was applied to determinate the analytes in wastewater and surface water
      and 10 compounds were detected in the range of 0.5-170 ng L(-1), being the
      ritalinic acid (the main metabolite of methylphenidate) the analyte detected in
      the highest concentrations.

PMID- 24925454
TI  - Partial rescue of memory deficits induced by calorie restriction in a mouse model
      of tau deposition.
AB  - Calorie restriction (CR) was shown previously to improve cognition and decrease
      pathology in transgenic mouse models with Alzheimer-like amyloid deposition. In
      the present study, we investigated the effects of CR on the Tg4510 model of tau
      deposition. Mice in the calorie restriction group had food intake gradually
      decreased until they reached an average of 35% body weight reduction. Body weight
      and food intake were monitored throughout the study. After being on their
      respective diets for 3 months, all animals were submitted to behavioral testing.
      Tg4510 mice fed ad libitum showed lower body weight than nontransgenic
      littermates despite their increased food intake. Additionally, Tg4510 showed
      increased locomotor activity in the open field regardless of diet. Calorie
      restricted Tg4510 mice performed significantly better than ad libitum fed mice in
      the novel object recognition test, suggesting improved short-term memory. CR
      Tg4510 mice also performed significantly better in contextual fear conditioning
      than mice fed ad libitum. However, in a modified version of the novelty test that
      allows for interaction with other mice instead of inanimate objects, CR was not
      able to rescue the deficit found in Tg4510 mice in this ethologically more
      salient version of the task. No treatment differences in motor performance or
      spatial memory were observed in the rotarod or radial arm water maze tests,
      respectively. Histopathological and biochemical assessments showed no diet
      induced changes in total or phospho-tau levels. Moreover, increased activation of
      both astrocytes and microglia in Tg4510 mice was not rescued by calorie
      restriction. Taken together, our data suggests that, despite an apparent rescue
      of associative memory, CR had no consistent effects on pathological outcomes of a
      mouse model of tau deposition. 

PMID- 24925455
TI  - Center of mass motion in swimming fish: effects of speed and locomotor mode
      during undulatory propulsion.
AB  - Studies of center of mass (COM) motion are fundamental to understanding the
      dynamics of animal movement, and have been carried out extensively for
      terrestrial and aerial locomotion. But despite a large amount of literature
      describing different body movement patterns in fishes, analyses of how the center
      of mass moves during undulatory propulsion are not available. These data would be
      valuable for understanding the dynamics of different body movement patterns and
      the effect of differing body shapes on locomotor force production. In the present
      study, we analyzed the magnitude and frequency components of COM motion in three
      dimensions (x: surge, y: sway, z: heave) in three fish species (eel, bluegill
      sunfish, and clown knifefish) swimming with four locomotor modes at three speeds
      using high-speed video, and used an image cross-correlation technique to estimate
      COM motion, thus enabling untethered and unrestrained locomotion. Anguilliform
      swimming by eels shows reduced COM surge oscillation magnitude relative to
      carangiform swimming, but not compared to knifefish using a gymnotiform locomotor
      style. Labriform swimming (bluegill at 0.5 body lengths/s) displays reduced COM
      sway oscillation relative to swimming in a carangiform style at higher speeds.
      Oscillation frequency of the COM in the surge direction occurs at twice the tail
      beat frequency for carangiform and anguilliform swimming, but at the same
      frequency as the tail beat for gymnotiform locomotion in clown knifefish. Scaling
      analysis of COM heave oscillation for terrestrial locomotion suggests that COM
      heave motion scales with positive allometry, and that fish have relatively low
      COM oscillations for their body size. 

PMID- 24925456
TI  - Schistosoma haematobium infections acquired in Corsica, France, August 2013.
AB  - A 12 year-old boy in Germany developed urinary schistosomiasis in January 2014.
      He had bathed in rivers in south-eastern Corsica five months earlier. Before this
      case, human schistomiasis had not been reported on the island, although its
      vector, the snail Bulinus truncatus, locally transmitted the zoonotic Schistosoma
      bovis. The boy's father excreted S. haematobium ova that were not viable; the
      boy's three siblings had a positive serology against schistosomes.

PMID- 24925457
TI  - Uptake and impact of a new live attenuated influenza vaccine programme in
      England: early results of a pilot in primary school-age children, 2013/14
      influenza season.
AB  - As part of the introduction and roll-out of a universal childhood live-attenuated
      influenza vaccination programme, 4-11 year-olds were vaccinated in seven pilot
      areas in England in the 2013/14 influenza season. This paper presents the uptake
      and impact of the programme for a range of disease indicators. End-of-season
      uptake was defined as the number of children in the target population who
      received at least one dose of influenza vaccine. Between week 40 2013 and week 15
      2014, cumulative disease incidence per 100,000 population (general practitioner
      consultations for influenza-like illness and laboratory-confirmed influenza
      hospitalisations), cumulative influenza swab positivity in primary and secondary
      care and cumulative proportion of emergency department respiratory attendances
      were calculated. Indicators were compared overall and by age group between pilot
      and non-pilot areas. Direct impact was defined as reduction in cumulative
      incidence based on residence in pilot relative to non-pilot areas in 4-11 year
      olds. Indirect impact was reduction between pilot and non-pilot areas in <4 year
      olds and >11 year-olds. Overall vaccine uptake of 52.5% (104,792/199,475) was
      achieved. Although influenza activity was low, a consistent, though not
      statistically significant, decrease in cumulative disease incidence and influenza
      positivity across different indicators was seen in pilot relative to non-pilot
      areas in both targeted and non-targeted age groups, except in older age groups,
      where no difference was observed for secondary care indicators.

PMID- 24925458
TI  - Emergence and molecular characterisation of non-toxigenic tox gene-bearing
      Corynebacterium diphtheriae biovar mitis in the United Kingdom, 2003-2012.
AB  - Non-toxigenic Corynebacterium diphtheriae have become increasingly recognised as
      emerging pathogens across Europe causing severe invasive disease. A subset of non
      toxigenic C. diphtheriae are 'non-toxigenic tox gene-bearing' (NTTB) strains;
      these strains are genotypically toxpositive, but do not express the protein. The
      circulation of NTTB strains was first observed during the 1990s upsurge of
      diphtheria in Eastern Europe but has not been reported in other European
      countries. Circulation of NTTB strains could be considered an increased risk for
      diphtheria and other related diseases, given their possible role as a tox gene
      reservoir with the theoretical risk of re-emerging toxin expression. Here we
      report the characterisation of 108 non-toxigenic C. diphtheriae biovar mitis
      isolates submitted to the World Health Organization (WHO) Global Reference Centre
      for Diphtheria at Public Health England, London, between 2003 and 2012, in order
      to determine the presence of NTTB strains. Using molecular methods, five NTTB
      isolates were identified; four human isolates (MLST type 212) and one isolate
      from a companion cat (MLST type 40). The emergence of these strains could
      indicate continuation of the circulation of potentially toxigenic strains and
      appropriate laboratory diagnostic methods should be used for detection. Given the
      complacency that currently exists in Europe awareness with regards to diphtheria
      diagnostics must be enhanced.

PMID- 24925459
TI  - Letter to the editor: Salmonella Stanley outbreaks--a prompt to reevaluate
      existing food regulations.

PMID- 24925462
TI  - Size effects in a relaxor: further insights into PMN.
AB  - Dielectric measurements of PbMg1/3Nb2/3O3 (PMN) powder and dense ceramics with
      grain sizes between 15 nm and two microns were carried out in a broad frequency
      range (20 Hz-1 GHz). Clear grain size dependence of relaxor behavior was
      evidenced. A progressive transformation from Vogel-Fulcher behavior towards the
      Arrhenius process in the PMN with reduction of grain size in both ceramics and
      powder was observed. In the case of ceramics we were able to extract deeper
      information from the distributions of relaxation times and an analysis using the
      Vogel-Fulcher law, revealing two main contributions: a fast part of distribution
      of relaxation times with a maximum close to 10(-11) s, which is almost grain-size
      independent and has a non-polar origin; whereas, a process with long relaxation
      times (in the time range of 10(-8) to 10(-5) s) is associated with the dynamics
      of the polar nanoregions and is strongly suppressed with reduction of grain size.
      The results of dielectric investigations are confirmed by Nuclear Magnetic
      Resonance experiments. 

PMID- 24925464
TI  - Improved survival with combined gemcitabine and S-1 for locally advanced
      pancreatic cancer: pooled analysis of three randomized studies.
AB  - BACKGROUND: The long-term prognosis for localized pancreatic cancer (PC) remains
      poor. Three randomized trials (GEST phase III, JACCRO PC-01 phase II and GEMSAP
      phase II) evaluated gemcitabine (Gem) with or without S-1 for patients with
      metastatic and locally advanced PC. A pooled analysis based on published data
      examined whether Gem with S-1 (GS) is superior to Gem alone in overall survival
      (OS) in patients with locally advanced PC. METHODS: Data were extracted on 193
      patients: 31 (JACCRO), 28 (GEMSAP), and 134 (GEST). OS was used for primary
      endpoint and progression-free survival (PFS) was used for secondary endpoint. A
      general variance-based method was used to estimate the pooled HR and 95% CI
      between GS (n = 96) and Gem (n = 97). RESULTS: Meta-analysis demonstrated that
      the overall risk of death was significantly different between the two
      chemotherapies (hazard ratio = 0.673, 95% confidence interval: 0.488-0.929, P =
      0.016). The median PFSs for GS and GEM in the JACCRO, GEMSAP, and GEST studies
      were 12.0, 12.6, and 10.7 months, and 4.1, 8.1, and 6.2 months, respectively (P =
      0.001). The random-effect pooled estimate for 165 patients showed the objective
      response rate (ORR) in the GS group (28.4%) was better in the Gem group (8.3%, P
      = 0.001). CONCLUSIONS: GS improved ORR, PFS and OS in patients with locally
      advanced PC over Gem alone. GS could become one of the front-line
      chemotherapeutic agents.

PMID- 24925463
TI  - What's special about task in dystonia? A voxel-based morphometry and diffusion
      weighted imaging study.
AB  - Numerous brain imaging studies have demonstrated structural changes in the basal
      ganglia, thalamus, sensorimotor cortex, and cerebellum across different forms of
      primary dystonia. However, our understanding of brain abnormalities contributing
      to the clinically well-described phenomenon of task specificity in dystonia
      remained limited. We used high-resolution magnetic resonance imaging (MRI) with
      voxel-based morphometry and diffusion weighted imaging with tract-based spatial
      statistics of fractional anisotropy to examine gray and white matter organization
      in two task-specific dystonia forms, writer's cramp and laryngeal dystonia, and
      two non-task-specific dystonia forms, cervical dystonia and blepharospasm. A
      direct comparison between both dystonia forms indicated that characteristic gray
      matter volumetric changes in task-specific dystonia involve the brain regions
      responsible for sensorimotor control during writing and speaking, such as primary
      somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus,
      middle/posterior cingulate cortex, and occipital cortex as well as the striatum
      and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by
      white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus,
      genu of the corpus callosum, anterior limb/genu of the internal capsule, and
      putamen. Conversely, gray matter volumetric changes in the non-task-specific
      group were limited to the left cerebellum (lobule VIIa) only, whereas white
      matter alterations were found to underlie the primary sensorimotor cortex,
      inferior parietal lobule, and middle cingulate gyrus. Distinct microstructural
      patterns in task-specific and non-task-specific dystonias may represent
      neuroimaging markers and provide evidence that these two dystonia subclasses
      likely follow divergent pathophysiological mechanisms precipitated by different
      triggers.

PMID- 24925465
TI  - Functional anatomy and feeding biomechanics of a giant Upper Jurassic pliosaur
      (Reptilia: Sauropterygia) from Weymouth Bay, Dorset, UK.
AB  - Pliosaurs were among the largest predators in Mesozoic seas, and yet their
      functional anatomy and feeding biomechanics are poorly understood. A new, well
      preserved pliosaur from the Kimmeridgian of Weymouth Bay (UK) revealed cranial
      adaptations related to feeding. Digital modelling of computed tomography scans
      allowed reconstruction of missing, distorted regions of the skull and of the
      adductor musculature, which indicated high bite forces. Size-corrected beam
      theory modelling showed that the snout was poorly optimised against bending and
      torsional stresses compared with other aquatic and terrestrial predators,
      suggesting that pliosaurs did not twist or shake their prey during feeding and
      that seizing was better performed with post-symphyseal bites. Finite element
      analysis identified biting-induced stress patterns in both the rostrum and lower
      jaws, highlighting weak areas in the rostral maxillary-premaxillary contact and
      the caudal mandibular symphysis. A comparatively weak skull coupled with
      musculature that was able to produce high forces, is explained as a trade-off
      between agility, hydrodynamics and strength. In the Kimmeridgian ecosystem, we
      conclude that Late Jurassic pliosaurs were generalist predators at the top of the
      food chain, able to prey on reptiles and fishes up to half their own length. 

PMID- 24925466
TI  - An assessment of diagnostic performance of a filter-based antibody-independent
      peripheral blood circulating tumour cell capture paired with cytomorphologic
      criteria for the diagnosis of cancer.
AB  - OBJECTIVES: Circulating tumour cells (CTCs) are reported to be predictive for
      prognosis and response to treatment in advanced lung cancer. However, the
      clinical utility of the CTCs detection remains unknown for early stage lung
      cancer as the number of CTCs is reported as low, providing challenges in
      identification. We have evaluated diagnostic performance of filtration-based
      technology using cytomorphologic criteria in patients undergoing surgery for lung
      cancer. MATERIAL AND METHODS: We processed blood from 76 patients undergoing
      surgery for known or suspected lung cancer using ScreenCell((r)) Cyto filter
      devices. Captured cells were stained using haematoxylin and eosin and
      independently assessed by two pathologists for the presence of atypical cells
      suspicious for cancer. Diagnostic performance was evaluated against pathologist
      reported diagnoses of cancer from surgically obtained specimens. RESULTS: Cancer
      was diagnosed in 57 patients (77.0%), including 32 with primary lung cancer
      (56.1%). The proportion of patients with early stage primary lung cancer in which
      CTCs were identified was 18 and 21 (56.3% and 65.6%, respectively) as reported by
      two pathologists. The agreement between the pathologists was 77.0% corresponding
      to a kappa-statistic of 53.7% indicating moderate agreement. No significant
      differences were found for the percentage of CTCs for primary and metastatic
      cancer as well as for cancer stages. On sensitivity weighted analysis, a
      sensitivity and specificity were 71.9% (95% CI 60.5-83.0) and 52.9% (95% CI 31.1
      77.0), respectively. On specificity weighted analysis, a sensitivity and
      specificity were 50.9% (95% CI 39.3-64.4) and 82.4% (60.4-96.2), respectively.
      CONCLUSION: The performance of the tested filter-based antibody-independent
      technology to capture CTCs using standard cytomorphologic criteria provides the
      potential of a diagnostic blood test for lung cancer.

PMID- 24925467
TI  - Conferences and convention centres' accessibility to people with disabilities.
AB  - OBJECTIVE: The purposes of this manuscript are to create awareness of problems of
      accessibility at meetings and conferences for people with disabilities, and to
      provide a checklist for organizers of conferences to make the event more
      accessible to people with disabilities. METHODS: We conducted a search of the
      grey literature for conference centres and venues that had recommendations for
      making the event more accessible. The types of disability included in this
      manuscript are those as a consequence of visual, hearing and mobility
      impairments. RESULTS: We provide a checklist to make meetings accessible to
      people with disabilities. The checklist is divided into sections related to event
      planning, venue accessibility, venue staff, invitations/registrations, greeting
      people with a disability, actions during the event, and suggestions for effective
      presenters. CONCLUSIONS: The checklist can be used by prospective organizers of
      conferences to plan an event and to ensure inclusion and participation of people
      with disabilities.

PMID- 24925469
TI  - Metal-free stabilization of monomeric antimony(I): a carbene-supported
      stibinidene.
AB  - A diamidocarbene was coordinated to an antimony(III) dichloride Lewis acid.
      Subsequent reduction with magnesium gave a monomeric, formally antimony(I)
      fragment that is supported by the diamidocarbene. Spectroscopic,
      crystallographic, and computational analyses demonstrated that the carbene ligand
      engages the antimony(I) center in pi-backbonding resulting in a short (2.068(7)
      A) Sb-C interaction that is comparable to those observed in known stibaalkenes.

PMID- 24925470
TI  - Comparison between diffusion-weighted MRI (DW-MRI) at 1.5 and 3 tesla: a phantom
      study.
AB  - PURPOSE: To compare DW-MRI between 1.5 and 3 Tesla (T) in terms of image quality,
      apparent diffusion coefficient (ADC), reproducibility, lesion-to-background
      contrast and signal-to-noise ratio (SNR), using a test object. MATERIALS AND
      METHODS: A spherical diffusion phantom was used for qualitatively assessing image
      quality and performing quantitative measurements between the two field strengths.
      RESULTS: Distortions and signal losses degraded image quality at 3T even when the
      protocols were optimized for minimum TE. The ADC, in the majority of the phantom
      compartments, was significantly different between 1.5T and 3T (P < 0.009), while
      the average coefficient of variation, excluding the phantom compartments affected
      by artifacts, was <1.3% at both field strengths. The lesion-to-background
      contrast was improved at 1.5T for images acquired with b = 1000 s/mm(2) and
      comparable contrast was achieved at 3T with higher b-values. The SNR gain at 3T
      could, in theory, be balanced by the increased number of signal excitations one
      can accommodate at 1.5T to perform DW-MRI within the same acquisition time and
      possibly improved image quality, when 3T systems with no parallel transmission
      are used. CONCLUSION: Further phantom and in vivo studies are required to
      investigate the utility of DW-MRI at 3T, if image quality and acquisition times
      comparable to the ones from 1.5T are assumed.

PMID- 24925468
TI  - Stem cell-derived motor neurons from spinal and bulbar muscular atrophy patients.
AB  - Spinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is a motor neuron
      disease caused by polyglutamine repeat expansion in the androgen receptor.
      Although degeneration occurs in the spinal cord and muscle, the exact mechanism
      is not clear. Induced pluripotent stem cells from spinal and bulbar muscular
      atrophy patients provide a useful model for understanding the disease mechanism
      and designing effective therapy. Stem cells were generated from six patients and
      compared to control lines from three healthy individuals. Motor neurons from four
      patients were differentiated from stem cells and characterized to understand
      disease-relevant phenotypes. Stem cells created from patient fibroblasts express
      less androgen receptor than control cells, but show androgen-dependent
      stabilization and nuclear translocation. The expanded repeat in several stem cell
      clones was unstable, with either expansion or contraction. Patient stem cell
      clones produced a similar number of motor neurons compared to controls, with or
      without androgen treatment. The stem cell-derived motor neurons had
      immunoreactivity for HB9, Isl1, ChAT, and SMI-32, and those with the largest
      repeat expansions were found to have increased acetylated alpha-tubulin and
      reduced HDAC6. Reduced HDAC6 was also found in motor neuron cultures from two
      other patients with shorter repeats. Evaluation of stably transfected mouse cells
      and SBMA spinal cord showed similar changes in acetylated alpha-tubulin and
      HDAC6. Perinuclear lysosomal enrichment, an HDAC6 dependent process, was
      disrupted in motor neurons from two patients with the longest repeats. SBMA stem
      cells present new insights into the disease, and the observations of reduced
      androgen receptor levels, repeat instability, and reduced HDAC6 provide avenues
      for further investigation of the disease mechanism and development of effective
      therapy. 

PMID- 24925471
TI  - Evaluation of antifreeze protein III for cryopreservation of Nili-Ravi (Bubalus
      bubalis) buffalo bull sperm.
AB  - Lower fertility in buffaloes with frozen-thawed semen is attributed to sperm
      damage that is believed to be due to formation of ice crystals during freeze/thaw
      process. It was hypothesized that antifreeze proteins in the extender may improve
      the post thaw quality of buffalo bull sperm. For this purpose, two separate
      experiments were conducted to evaluate antifreeze proteins III (AFP III) at 0
      (control), 0.1, 1 and 10 MUg/mL (Experiment I) and 0 (control), 0.01, 0.1 and 1
      MUg/mL (Experiment II) for its effect on post thaw quality of buffalo bull semen.
      Semen was collected from three Nili-Ravi buffalo (Bubalus bubalis) bulls with
      artificial vagina (42  degrees C) for three weeks (replicate) per experiment. For
      each experiment, qualifying ejaculates (6 ejaculates/bull) were divided into four
      aliquots and diluted (at 37  degrees C having 50 * 10(6) sperm/mL) in tris-citric
      acid extender containing above mentioned concentrations of AFP III. Diluted semen
      was cooled to 4  degrees C in 2 h, equilibrated for 4 h, filled in 0.5 mL straws,
      kept over liquid nitrogen vapors for 10 min and plunged in the liquid nitrogen.
      After 24 h of storage, semen straws were thawed at 37  degrees C for 30 s to
      assess sperm progressive motility (SM), plasma membrane integrity (PMI),
      viability (live sperm with intact acrosome) and normal epical ridge (NAR). In
      experiment I, improvement (P<0.05) in percentage SM and sperm PMI was recorded in
      extender containing 0.1 MUg/mL AFP III compared to control, the higher
      concentrations (1 MUg/mL and 10 MUg/mL) being inefficient. While evaluating the
      lower concentration (experiment II), 0.01 MUg/mL of AFP III in the extender it
      was found to be ineffective to improve semen quality parameters, while 0.1 MUg/mL
      AFP III in extender was found better in terms of progressive motility and plasma
      membrane integrity of buffalo bull semen compared to control. Sperm viability and
      NAR remained similar (P>0.05) in extenders containing different concentrations of
      AFP III and control in both of experiments. In conclusion addition of AFP III in
      the extender at 0.1 MUg/mL improved the progressive motility and plasma membrane
      integrity of cryopreserved buffalo bull semen.

PMID- 24925473
TI  - Natural loss-of-function mutation of EDR1 conferring resistance to tomato powdery
      mildew in Arabidopsis thaliana accession C24.
AB  - To screen for potentially novel types of resistance to tomato powdery mildew
      Oidium neolycopersici, a disease assay was performed on 123 Arabidopsis thaliana
      accessions. Forty accessions were fully resistant, and one, C24, was analysed in
      detail. By quantitative trait locus (QTL) analysis of an F2 population derived
      from C24 * Sha (susceptible accession), two QTLs associated with resistance were
      identified in C24. Fine mapping of QTL-1 on chromosome 1 delimited the region to
      an interval of 58 kb encompassing 15 candidate genes. One of these was Enhanced
      Disease Resistance 1 (EDR1). Evaluation of the previously obtained edr1 mutant of
      Arabidopsis accession Col-0, which was identified because of its resistance to
      powdery mildew Golovinomyces cichoracearum, showed that it also displayed
      resistance to O. neolycopersici. Sequencing of EDR1 in our C24 germplasm
      (referred to as C24-W) revealed two missing nucleotides in the second exon of
      EDR1 resulting in a premature stop codon. Remarkably, C24 obtained from other
      laboratories does not contain the EDR1 mutation. To verify the identity of C24-W,
      a DNA region containing a single nucleotide polymorphism (SNP) unique to C24 was
      sequenced showing that C24-W contains the C24-specific nucleotide. C24-W showed
      enhanced resistance to O. neolycopersici compared with C24 not containing the
      edr1 mutation. Furthermore, C24-W displayed a dwarf phenotype, which was not
      associated with the mutation in EDR1 and was not caused by the differential
      accumulation of pathogenesis-related genes. In conclusion, we identified a
      natural edr1 mutant in the background of C24. 

PMID- 24925474
TI  - Babesia spp. in European wild ruminant species: parasite diversity and risk
      factors for infection.
AB  - Babesia are tick-borne parasites that are increasingly considered as a threat to
      animal and public health. We aimed to assess the role of European free-ranging
      wild ruminants as maintenance mammalian hosts for Babesia species and to
      determine risk factors for infection. EDTA blood was collected from 222 roe deer
      (Capreolus c. capreolus), 231 red deer (Cervus e. elaphus), 267 Alpine chamois
      (Rupicapra r. rupicapra) and 264 Alpine ibex (Capra i. ibex) from all over
      Switzerland and analysed by PCR with pan-Babesia primers targeting the 18S rRNA
      gene, primers specific for B. capreoli and Babesia sp. EU1, and by sequencing.
      Babesia species, including B. divergens, B. capreoli, Babesia sp. EU1, Babesia
      sp. CH1 and B. motasi, were detected in 10.7% of all samples. Five individuals
      were co-infected with two Babesia species. Infection with specific Babesia varied
      widely between host species. Cervidae were significantly more infected with
      Babesia spp. than Caprinae. Babesia capreoli and Babesia sp. EU1 were mostly
      found in roe deer (prevalences 17.1% and 7.7%, respectively) and B. divergens and
      Babesia sp. CH1 only in red deer. Factors significantly associated with infection
      were low altitude and young age. Identification of Babesia sp. CH1 in red deer,
      co-infection with multiple Babesia species and infection of wild Caprinae with B.
      motasi and Babesia sp. EU1 are novel findings. We propose wild Caprinae as
      spillover or accidental hosts for Babesia species but wild Cervidae as mammalian
      reservoir hosts for B. capreoli, possibly Babesia sp. EU1 and Babesia sp. CH1,
      whereas their role regarding B. divergens is more elusive.

PMID- 24925475
TI  - Dried artichoke bracts in rabbits nutrition: effects on the carcass
      characteristics, meat quality and fatty-acid composition.
AB  - In this study, the effects of the inclusion of artichoke bracts (AB) in rabbit
      diets on the carcass characteristics and rabbit meat quality were studied. A
      total of 120 rabbits aged 38 days were used and divided into three groups that
      were fed with different isonitrogenous and isocaloric diets supplemented with AB
      at 0%, 5% and 10%. The animals were single housed in wire cages at a temperature
      of 22+/-2 degrees C and had free access to clean drinking water. At 96 days of
      age, 12 rabbits/group were slaughtered in an experimental slaughterhouse without
      fasting. The carcass was weighed and the weights of the skin and full
      gastrointestinal tract were recorded. Carcasses were chilled at +4 degrees C for
      24 h in a refrigerated room. The chilled carcass weight (CCW), dressing out
      percentage (CCW as percentage of slaughter weight), and the ratio of the head and
      liver were determined as a percentage of CCW. The reference carcass weight was
      also calculated. Carcasses were halved and the two longissimus dorsi (LD) muscles
      were excised. The left LD muscle was divided into two parts. The fore part was
      used to measure pH, colour and cooking losses. The hind part of the left LD was
      vacuum-packed, frozen at -20 degrees C and then freeze-dried. Proximate
      composition, fatty-acid profile and thiobarbituric acid-reactive substances
      values were determined on freeze-dried samples. Results showed that carcass
      characteristics, LD muscle traits and its oxidative status were not affected by
      the AB supplementation, except for the meat ether extract content that increased
      from 0.68% to 0.94% on fresh matter basis with the increase of the AB
      supplementation (P<0.01). The alpha-linolenic acid proportion decreased with the
      increase of the AB supplementation from 3.58% to 2.59% in the LD muscle and from
      4.74% to 3.62% in the perirenal fat, whereas the n-6/n-3 ratio increased
      significantly with increasing AB inclusion from 7.15 to 10.20 in the LD muscle
      and from 6.68 to 9.35 in the perirenal fat (P<0.01). Furthermore, no significant
      difference was found in preference among meat samples from each group. The
      enrichment of the rabbit's diet with AB allows the production of rabbit meat with
      a good degree of unsaturation and low saturation, even if the n-6/n-3 ratio was
      slightly worse. 

PMID- 24925476
TI  - Klebsiella pneumoniae pharyngitis mimicking malignancy: a diagnostic dilemma.
AB  - Acute pharyngitis is a common disease. However, acute pharyngitis caused by
      Klebsiella pneumoniae with a gross appearance mimicking hypopharyngeal malignancy
      has never previously been reported. We report the case of a 57-year-old man with
      a right hypopharyngeal tumor which was disclosed by fiberoptic laryngoscopy and
      computed tomography scan. However, both the frozen and final pathologies showed
      no evidence of malignant cells, and a bacterial culture revealed the growth of K.
      pneumoniae. The hypopharyngeal lesion completely regressed after 2 weeks of
      antibiotic treatment. Clinicians should perform biopsy along with tissue culture
      for tumor-like lesions because infectious agents can lead to lesions with
      malignancy-like appearance.

PMID- 24925477
TI  - Physical and mental health comorbidity is common in people with multiple
      sclerosis: nationally representative cross-sectional population database
      analysis.
AB  - BACKGROUND: Comorbidity in Multiple Sclerosis (MS) is associated with worse
      health and higher mortality. This study aims to describe clinician recorded
      comorbidities in people with MS. METHODS: 39 comorbidities in 3826 people with MS
      aged >=25 years were compared against 1,268,859 controls. Results were analysed
      by age, gender, and socioeconomic status, with unadjusted and adjusted Odds
      Ratios (ORs) calculated using logistic regression. RESULTS: People with MS were
      more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38
      1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47
      1.77) non-MS chronic conditions than controls, and greater mental health
      comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of
      physical comorbidities rose. Cardiovascular conditions, including atrial
      fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI
      0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR
      0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were
      significantly less common in people with MS. CONCLUSION: People with MS have
      excess multiple chronic conditions, with associated increased mental health
      comorbidity. The low recorded cardiovascular comorbidity warrants further
      investigation.

PMID- 24925478
TI  - Uric acid inhibition of dipeptidyl peptidase IV in vitro is dependent on the
      intracellular formation of triuret.
AB  - Uric acid affects endothelial and adipose cell function and has been linked to
      diseases such as hypertension, metabolic syndrome, and cardiovascular disease.
      Interestingly uric acid has been shown to increase endothelial progenitor cell
      (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC
      mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase
      (DPP)IV, we examined the effect uric acid will have on CD26/DPPIV activity. Uric
      acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial
      cells but not human recombinant (hr) CD26/DPPIV. However, triuret, a product of
      uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV.
      Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased
      the ability of uric acid to inhibit cell associated CD26/DPPIV, respectively.
      Finally, protein modeling demonstrates how triuret can act as a small molecule
      inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric
      acid reaction product has been shown to affect enzymatic activity and suggests a
      novel avenue of research in the role of uric acid in the development of
      clinically important diseases. 

PMID- 24925479
TI  - Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal
      differential expression patterns in cancer and low antigen expression in normal
      tissues.
AB  - There is a considerable interest for the discovery and characterization of tumor
      associated antigens, which may facilitate antibody-based pharmacodelivery
      strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted
      proteins, which have previously been reported to be overexpressed during
      remodeling typical for wound healing and tumor progression and to possibly play a
      functional role in cell proliferation, migration and apoptosis. To our knowledge,
      a complete immunohistochemical characterization of thrombospondins levels in
      normal rodent tissues has not been reported so far. Using antibody phage
      technology, we have generated and characterized monoclonal antibodies specific to
      murine thrombospondin-1 and thrombospondin-2, two antigens which share 62%
      aminoacid identity. An immunofluorescence analysis revealed that both antigens
      are virtually undetectable in normal mouse tissues, except for a weak staining of
      heart tissue by antibodies specific to thrombospondin-1. The analysis also showed
      that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in
      nude mice, while it was only barely detectable in 3/8 murine tumors grafted in
      immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2
      revealed a much lower level of expression of this antigen in cancer specimens.
      Our analysis resolves ambiguities related to conflicting reports on
      thrombosponding expression in health and disease. Based on our findings,
      thrombospondin-1 (and not thrombospondin-2) may be considered as a target for
      antibody-based pharmacodelivery strategies, in consideration of its low
      expression in normal tissues and its upregulation in cancer. 

PMID- 24925480
TI  - Absolute and relative temporal order memory for performed activities following
      stroke.
AB  - Reconstructing the temporal order of events is a crucial part of episodic memory.
      The temporal dimension, however, is often discarded in clinical settings, and
      measurements of true temporal aspects of episodic memory are scarce. The present
      study assessed temporal memory in stroke patients and in age- and education
      matched healthy controls. Both groups underwent a standardized neuropsychological
      examination. We asked participants afterwards to reconstruct the order of tests
      they had performed, measured in absolute temporal order (event placed on correct
      moment in sequence) and relative temporal order (event placed correctly relative
      to directly preceding and following events). The aim of the study was to examine
      how serial-position curve effects (measuring absolute temporal order anchored in
      exact time) and how relative temporal order memory (anchored to other events) may
      differ in a group of cerebral stroke patients. Another aim was to link temporal
      order memory deficits with established neuropsychological measures of cognitive
      functioning. Although item identification was comparable in both groups, absolute
      temporal order memory was impaired in patients: A total of 43% of the patients
      lacked the expected primacy and recency effects (serial position effect). In
      addition, relative temporal order memory was affected in this group as well, F(1,
      70) = 4.08, p < .05; 25% of the patients were impaired in reconstructing the
      relative temporal order (p = .019, Fisher's Exact Test). Both absolute and
      relative temporal order memory performance related to the domains of executive
      functioning and memory. Our results suggest that it is important to test both
      absolute and relative temporal order memory, especially because these types of
      memory depend on different anchors, either on time or on adjacent events. 

PMID- 24925481
TI  - Impact-induced shock and the formation of natural quasicrystals in the early
      solar system.
AB  - The discovery of a natural quasicrystal, icosahedrite (Al63Cu24Fe13), accompanied
      by khatyrkite (CuAl2) and cupalite (CuAl) in the CV3 carbonaceous chondrite
      Khatyrka has posed a mystery as to what extraterrestrial processes led to the
      formation and preservation of these metal alloys. Here we present a range of
      evidence, including the discovery of high-pressure phases never observed before
      in a CV3 chondrite, indicating that an impact shock generated a heterogeneous
      distribution of pressures and temperatures in which some portions reached at
      least 5 GPa and 1,200  degrees C. The conditions were sufficient to melt Al-Cu
      bearing minerals, which then rapidly solidified into icosahedrite and other Al-Cu
      metal phases. The meteorite also contains heretofore unobserved phases of iron
      nickel and iron sulphide with substantial amounts of Al and Cu. The presence of
      these phases in Khatyrka provides further proof that the Al-Cu alloys are natural
      products of unusual processes that occurred in the early solar system.

PMID- 24925482
TI  - The development of behaviour patterns and temperament in dairy heifers.
AB  - Observations were carried out on a group of twenty autumn born Friesian heifer
      calves from birth until calving at about 25 months of age. During rearing they
      experienced several rearing conditions; (I) Calf house, where from 48 hrs of age
      they were individually penned. (II) Group housed Indoors. At weaning they were
      housed in pens in groups of 10-20 animals and fed hay or silage ad libitum plus
      some concentrate food. (III) Grazing out doors (HGI) from spring to autumn in
      groups of 15-30 animals and moved to fresh pastures at about 2 week intervals.
      (IV) Housed indoors in large groups of 70-80 animals in a yard with access to
      covered or indoor cubicles, and fed silage ad lib. During this period they were
      artificially inseminated. (V) Second grazing period. In the following spring they
      were kept in large groups for grazing. Focal animal sampling to allow sequence
      analysis of behaviour was performed and a time base was used to estimate time
      budgets. In addition the temperament of each animal was assessed by recording its
      reaction to being touched. The development of behaviour was strongly influenced
      by changes between rearing conditions but generally stabilized rapidly within a
      particular husbandry condition. The time spent resting was greater when the
      animals were in the fields than indoors. Ruminating increased over the first 20
      weeks and then stabilized. In the calf house the time spent in investigation
      increased up to 4-5 weeks and then decreased while the frequency of investigation
      increased. Grooming generally decreased over the study period. In the calf house
      calf licking increased but after grouping this decreased and rubbing of the body
      increased. Social encounters tended to decrease with age. The development of
      temperament as defined later in the text here appears to be determined at an
      early age and to be stable thereafter. Sequence analysis showed that behavioural
      sequences became shorter and less variable in content and that as the animal
      matured fewer behavioural activities were associated in any sequence and that
      these showed an increase in their degree of association. 

PMID- 24925483
TI  - Responses to successive test of induction of maternal behaviour in hens.
AB  - This experiment was undertaken to find out if the kinetics of the behaviours
      which emerge gradually during a first experiment of maternal induction was
      modified by a second and then a third similar experiment, or not. In addition,
      during the second experiment the behaviour of experienced hens was compared to
      that of naive hens of the same strain undergoing their first induction. Three
      important facts appeared : (i) In each series, maternal behaviours (accepting
      contact of chicks, clucking) emerged gradually (significant day effect). (ii)
      Repeating these experiments revealed on the whole neither increase nor decline of
      hens' responsiveness towards chicks (negligible series effect). No significant
      difference between naive hens and hens having already had a first induction
      experience was found. (iii) There was an important difference between hens
      concerning their delay in adopting, and a good stability of individual profiles
      was found between series (significant hen effect). 

PMID- 24925484
TI  - Effects of the sex of the resident adult and of the sex of the opponent on
      interactions in Mongolian gerbils (Meriones unguiculatus).
AB  - Mated pairs of Mongolian gerbils were rejoined by two of their own young, one of
      each sex, after periods of separation starting when the young were four or seven
      weeks old and lasting either one or four weeks. An additional sub-group of
      litters was separated when six weeks old, for a period of separation of two
      weeks. In another group of mated-pairs, mated-adults were introduced and observed
      in the same way. Occurrences of sniffing, opposition and pursuit between each
      adult and each intruder was noted over a period of one hour. A clear effect of
      the sex of the resident adult on agonistic behaviour was evident. The adult
      female develops its agonistics acts sooner than the male i.e. it is more
      responsive than the male to a short duration of separation from the juveniles.
      The adult female shows either pursuit or opposition to juveniles but shows almost
      no agonistic behaviour in the presence of unrelated adults. As for the adult
      male, its agonistic acts begin to appear after four weeks of separation and
      persist with very frequent opposition, in adult-adult meetings. The sex of the
      intruder only appeared to be a significant factor after four weeks of separation.
      After four weeks of separation, opposition of the adult male to the young male
      was significantly higher than that to the young female. Sniffing of the young
      male by the adult female was significantly higher than that of the young female.
      With the same period of separation, but with opponents of eleven weeks, as well
      as in meetings of adults, each resident adult had a greater number of
      interactions with the intruder of the same sex. 

PMID- 24925485
TI  - Spontaneous light or dark preference in albino mice?
AB  - The present experiment examined spontaneous visual choice behaviour and
      acquisition of a positively reinforced visual discrimination task in Swiss albino
      mice. In experiment I animals were given 4 consecutive trials in which they could
      freely enter either a dimly illuminated or a darkened arm of a Y-maze; the
      position of the light stimulus was randomized across trials. D groups and L
      groups were tested during the dark and the light period of the day respectively.
      Results revealed a significant spontaneous preference for the illuminated arm of
      the maze, independent of the testing period. It is suggested that the dim light
      has a reinforcing value because it provides additional information about a novel
      environment. In a second experiment an appetitive visual discrimination task was
      carried out in the same Y-maze. After a pretraining period, half the animals were
      reinforced in the illuminated arm and half were reinforced in the darkened one,
      on five consecutive days. On the first test session all groups of animals chose
      the illuminated arm significantly more frequently, whereas light/dark choices
      reached chance level on the last test session. Discrimination learning was not
      acquired and a behavioural analysis revealed an increasing tendency to a side
      preference across testing. 

PMID- 24925486
TI  - Acquisition and retention of habituation as a function of intertrial interval
      duration during training in the blowfly.
AB  - The influence of the duration of the interval between successive stimulations
      during habituation training on the dynamics of motor response decrement and its
      retention over time has been studied in the blowfly, Calliphora vomitoria . The
      intertrial interval (ITI) duration during training was either 7, 15, 30, 60 or
      120 seconds. After a rest period of 30 minutes, a second session was given with
      the same ITI duration of 30 seconds for all groups. The response decrement
      observed during training is faster the longer the ITI duration. At the end of
      this session, the lower response level is reached with an ITI of 60 seconds.
      After the rest period, the lower responsiveness is observed in the animals which
      have been trained with the longer ITI. These results are discussed with reference
      to the dual-process theory of habituation, which can account for the results
      obtained during training, and memory-centered models to interpret the influence
      of ITI duration on retention performance. 

PMID- 24925487
TI  - Probabilistic choice: A simple invariance.
AB  - When subjects must choose repeatedly between two or more alternatives, each of
      which dispenses reward on a probabilistic basis (two-armed bandit ), their
      behavior is guided by the two possible outcomes, reward and nonreward. The
      simplest stochastic choice rule is that the probability of choosing an
      alternative increases following a reward and decreases following a nonreward
      (reward following ). We show experimentally and theoretically that animal
      subjects behave as if the absolute magnitudes of the changes in choice
      probability caused by reward and nonreward do not depend on the response which
      produced the reward or nonreward (source independence ), and that the effects of
      reward and nonreward are in constant ratio under fixed conditions (effect-ratio
      invariance )--properties that fit the definition of satisficing . Our
      experimental results are either not predicted by, or are inconsistent with, other
      theories of free-operant choice such as Bush-Mosteller, molar maximization,
      momentary maximizing, and melioration (matching). 

PMID- 24925488
TI  - Possible use of environmental gradients in orientation by homing wood mice,
      Apodemus sylvaticus.
AB  - 51 wood mice, Apodemus sylvaticus, tagged with chemoluminescent bulbs, were
      visually tracked in a series of night homing experiments. The mice did not go
      straight towards home, but wandered around the release area and covered distances
      equal to twice the radial lengths recorded. In the course of their walk, they
      orientated preferentially towards landscapes which resembled their usual habitat,
      irrespective of where their actual homeward direction lay. In spite of the
      randomness of their paths, homing success was good, but detailed analysis of
      homing time showed that the homing performances of the mice depended on the
      direction in which they vanished in the course of the observation period. The
      good fit of observed orientations with those obtained by computer simulation of
      klinokinesis along an axial gradient, and field observation of a vegetational
      gradient in the study area, are both consistent with the hypothesis that homing
      may have resulted from wandering, locally biased by a klinokinetic effect. 

PMID- 24925489
TI  - Time-compensated celestial orientation in the cricket Pteronemobius lineolatus.
AB  - By varying the time difference between capture and release, we can show that
      swimming crickets Pteronemobius lineolatus are able to time compensate for the
      apparent azimuthal change of the sun's position. 

PMID- 24925491
TI  - Predictors of dieting and disordered eating behaviors from adolescence to young
      adulthood.
AB  - PURPOSE: To identify personal and socioenvironmental factors associated with the
      persistence of dieting or disordered eating from adolescence to young adulthood
      and factors associated with the initiation of dieting or disordered eating during
      young adulthood. METHODS: Participants (n = 4,746) completed EAT-I surveys as
      adolescents; EAT-III surveys were completed 10 years later by 1,902 of the
      original participants (1,082 females and 820 males). RESULTS: Study results
      indicate that there are personal factors, including weight concerns, weight
      importance, depressive symptoms and body satisfaction, present during adolescence
      that are predictive of an individual's engagement in dieting or disordered eating
      behaviors 10 years later. For example, among both males and females, weight
      importance was found to be predictive of continued dieting and disordered eating
      from adolescence through young adulthood. For example, 26.1% of males with low
      levels of weight concern at baseline reported engaging in persistent disordered
      eating as compared with 60.4% of males with high levels of weight concern at
      baseline (prevalence difference: 34.3; 95% confidence interval: 10.5-58.1; p <
      .01). Parental weight concerns, peer dieting, and weight teasing at baseline were
      not found to be predictive of dieting or disordered eating at 10-year follow-up.
      CONCLUSIONS: Personal factors identified during adolescence were found to be
      predictive of both persistent dieting and disordered eating from adolescence into
      young adulthood, as well as initiation of these behaviors during young adulthood.
      In particular, weight concerns and weight importance were found to be predictive
      in most models providing support for inclusion of these factors in adolescent
      health screening.

PMID- 24925492
TI  - TeenDrivingPlan effectiveness: the effect of quantity and diversity of supervised
      practice on teens' driving performance.
AB  - PURPOSE: The large contribution of inexperience to the high crash rate of newly
      licensed teens suggests that they enter licensure with insufficient skills. In a
      prior analysis, we found moderate support for a direct effect of a web-based
      intervention, the TeenDrivingPlan (TDP), on teens' driving performance. The
      purpose of the present study was to identify the mechanisms by which TDP may be
      effective and to extend our understanding of how teens learn to drive. METHODS: A
      randomized controlled trial conducted with teen permit holders and parent
      supervisors (N = 151 dyads) was used to determine if the effect of TDP on driver
      performance operated through five hypothesized mediators: (1) parent-perceived
      social support; (2) teen-perceived social support; (3) parent engagement; (4)
      practice quantity; and (5) practice diversity. Certified driving evaluators,
      blinded to teens' treatment allocation, assessed teens' driving performance 24
      weeks after enrollment. Mediator variables were assessed on self-report surveys
      administered periodically over the study period. RESULTS: Exposure to TDP
      increased teen-perceived social support, parent engagement, and practice
      diversity. Both greater practice quantity and diversity were associated with
      better driving performance, but only practice diversity mediated the relationship
      between TDP and driver performance. CONCLUSIONS: Practice diversity is feasible
      to change and increases teens' likelihood of completing a rigorous on-road
      driving assessment just before licensure. Future research should continue to
      identify mechanisms that diversify practice driving, explore complementary ways
      to help families optimize the time they spend on practice driving, and evaluate
      the long-term effectiveness of TDP.

PMID- 24925494
TI  - Behavioral resistance to haloperidol and clozapine.
AB  - Using a procedure to assess behavioral resistance to change, the effects of two
      drugs (haloperidol and clozapine) were compared to each other and to the effect
      of response-independent food delivered between multiple-schedule components.
      Using rats as subjects, responding in one component was maintained on a variable
      interval 30-s schedule, whereas responding in another component was maintained on
      a variable-interval 30-s schedule that operated concurrently with a variable-time
      30-s schedule. Consistent with previous findings, responding in the component
      with the greater overall amount of reinforcement displayed the greater resistance
      to response-independent food delivery. Similarly, increasing the dose of
      haloperidol or clozapine increased the overall extent of disruption (relative to
      baseline levels), with the greatest disruption occurring to responding in the
      component associated with the smaller overall amount of food reinforcement. Thus,
      as with the disruption caused by alterations in reinforcement conditions, the
      extent of disruption to reinforced responding caused by haloperidol and clozapine
      is specifically dependent upon baseline reinforcement conditions rather than
      baseline response rates. 

PMID- 24925495
TI  - Very brief exposure to visual distal cues is sufficient for young mice to
      navigate in the Morris water maze.
AB  - This set of two experiments investigated the capacities of C57BL/6 mice to
      integrate visual distal information. In the first study, we submitted mice of two
      ages (22 and 65 day old) to the place learning version of the Morris water task.
      After the acquisition phase, the mice were put in one of three conditions: (1) a
      classical probe test (only the platform was removed); (2) a rotating probe test
      (the platform was removed and the distal visual cues were rotated from 90 degrees
      ); and (3) a suppressing probe test (both the platform and the cues were
      removed). The results indicated that whatever their ages mice used preferentially
      the visual cues to locate the platform. In the second experiment, groups of mice
      of either age were subjected to 1 of 4 procedures. Separate groups of mice were
      required to escape onto a platform located in a fixed position either hidden or
      visible. Following escape, animals were either given unrestricted visual access
      to the extramaze environment for the duration of the platform interval (60 s,
      place learning and cue+place learning groups), or denied this opportunity by
      switching off the room lights (place-lights learning and cue+place-lights
      learning groups). The results of this second experiment indicate that whatever
      their age and the procedure used, mice performed equally and exhibited a spatial
      bias during the probe test. All together, these results suggest that as early as
      22 days of age, mice integrate visual distal information especially while on the
      way to the goal, and this even so this information was not necessary to solve the
      task. 

PMID- 24925493
TI  - Use of a medically supervised injection facility among street youth.
AB  - PURPOSE: Supervised injecting facilities (SIFs) provide a sanctioned space for
      injection drug users and are associated with decreased overdose mortality and HIV
      risk behaviors among adults. Little is known about SIF use among youth. We
      identified factors associated with use of the Vancouver SIF, the only such
      facility in North America, among street youth. METHODS: From September 2005 to
      May 2012, we collected data from the At-Risk Youth Study, a prospective cohort of
      street youth in Vancouver, BC, Canada. Eligible youth were aged 14-26 years.
      Participants reporting injection completed questionnaires at baseline and
      semiannually. We used generalized estimating equation logistic regression to
      identify factors associated with SIF use. RESULTS: During the study period, 42.3%
      of 414 injecting youth reported use of the SIF at least once. Of all SIF-using
      youth, 51.4% went to the facility at least weekly, and 44.5% used it for at least
      one-quarter of all injections. SIF-using youth were more likely to live or spend
      time in the neighborhood surrounding the SIF (adjusted odds ratio [AOR], 3.29;
      95% confidence interval [CI], 2.38-4.54), to inject in public (AOR, 2.08; 95% CI,
      1.53-2.84), or to engage in daily injection of heroin (AOR, 2.36; 95% CI, 1.72
      3.24), cocaine (AOR, 2.44; 95% CI, 1.34-4.45), or crystal methamphetamine (AOR,
      1.62; 95% CI, 1.13-2.31). CONCLUSIONS: This study, the first to examine SIF use
      among street youth in North America, demonstrated that the facility attracted
      high-frequency young drug users most at risk of blood-borne infection and
      overdose and those who otherwise inject in public spaces.

PMID- 24925496
TI  - 'Subjective lengthening' during repeated testing of a simple temporal
      discrimination.
AB  - Three experiments investigated behavioural changes, using a temporal
      generalization paradigm with human subjects, resulting from repeated testing
      without feedback. In Experiment 1, different groups received five initial
      presentations of a 400 ms 500 Hz tone, or a 400 ms 14*14 cm blue square,
      identified as having a standard duration, then received blocks of testing where
      stimuli with durations shorter than, longer than, or equal to the standard were
      presented. Subjects had to judge whether each presented stimulus was the standard
      duration, but no feedback was given. Temporal generalization gradients
      (proportion of identifications of a stimulus as being the standard, plotted
      against stimulus duration) shifted progressively to the right during the test
      phase (i.e. longer stimuli tended to be identified as the standard as testing
      proceeded) in the visual stimulus condition. Experiment 2 used a generalization
      procedure to examine, with different subject groups, behavioural changes when
      either the duration, or the length, of a blue bar presented on the computer
      screen was the basis of judgement. Across trials, both length and duration could
      vary, but for one group only duration was relevant whereas for the other group
      only length was. Generalization gradients shifted systematically to the right
      only in duration judgements. Experiment 3 replicated the rightward shift in
      generalization gradients when the duration of visual stimuli was measured, and in
      addition used a self-rating scale derived from Thayer [Thayer, R.E., 1967.
      Measurement of activation through self-report. Psych. Rep. 20, 663-678.) to
      measure subjects' arousal. This declined systematically as testing proceeded,
      suggesting that the shift in temporal generalization gradient was probably caused
      by an arousal-induced change in internal clock speed. 

PMID- 24925497
TI  - Sample frequency and sample duration as sources of stimulus control in delayed
      matching to sample.
AB  - Three experiments examined sample duration and sample presentation frequency
      (SPF) on choice in a two-alternative, delayed matching-to-sample task. In
      Experiment 1, using a behavioural-detection approach, we demonstrated bias toward
      the more frequent sample, despite the conditional probability of reinforcement
      for a correct match on any particular trial remaining at 1.0 for both stimuli.
      Although retention-interval duration influenced both discriminability and bias in
      Experiment 1, bias was independent of retention interval in two subsequent
      experiments. Experiments 2 and 3 replicated the effects of SPF on bias, and
      demonstrated that discriminability of the stimuli was not influenced by the SPF
      manipulation. Experiment 2 also investigated the effect of a within-session
      variation in sample duration on discriminability and bias measures, both with and
      without unequal SPFs. Discriminability was enhanced to both the short and long
      samples of the unequal sample-durations' condition relative to discrimination in
      conditions where samples were presented for equal durations. Bias generated by
      varying SPF was independent of sample-duration effects and of retention-interval
      duration. Taken together, these data suggest independent and qualitatively
      different effects of sample frequency and sample duration on matching behaviour:
      Sample frequency has its effect on bias measures, while sample duration
      influences discriminability. We suggest that sample frequency is a global task
      factor influencing reference memory, and sample duration is a trial-specific,
      conditional discrimination factor, involving short-term or working memory
      processing. 

PMID- 24925498
TI  - Does the Pyrenean salamander Euproctus asper use chemical cues for sex
      identification and mating behaviour?
AB  - This paper examined the potentiality of chemical cues for sex identification and
      mating activity in Euproctus asper. The study tested the ability of males and
      females to distinguish between the odour of animals of their own sex and that of
      animals of the opposite sex, as it was carried to them by water flowing over
      another animal. Their ability to distinguish between water flowing over another
      E. asper and water flowing over a control, where no other animal was present, was
      also tested. Then, the study tested their ability to distinguish between the
      diffusing odour of animals of their own sex, that of animals of the opposite sex,
      and that of a control, where no other animal was present. There was no evidence
      that males and females identify their mates using chemical cues. Observations of
      the courtship behaviour were also carried out. Mating seems to be induced by the
      male's display of his tail when he captures the female as she passes near him, to
      form an amplexus, without any obvious preliminary. On the basis of these data,
      the question whether the mate identification occurs during the amplexus in this
      species was raised. 

PMID- 24925499
TI  - Speeding up and (...relatively...) slowing down an internal clock in humans.
AB  - Two experiments used click-trains to manipulate the subjective duration of
      stimuli they preceded, in attempts to demonstrate relative slowing down of the
      pacemaker of a hypothesized internal clock. Experiment 1 used a pair comparison
      procedure, where two tones presented on each trial in fact had the same duration.
      In the conditions of particular interest, the first tone was preceded by clicks
      (thus putatively timed with a faster clock), the other presented without (thus
      timed normally). The reverse condition (no-clicks/clicks) was also used.
      Judgements of the relative duration of the stimuli were shifted in both
      directions (i.e. first tone longer than second and vice versa) by the
      manipulation, consistent with relative speeding up and slowing down of the
      pacemaker. Experiment 2 used the popular bisection method, with 200- and 800-ms
      tones used as the Short and Long standards for the task. After standard
      presentations, subjects were required to classify a range of comparison stimuli
      (from 200 to 800 ms in 100-ms steps) in terms of their similarity to one or the
      other of the standards. In one condition the comparison stimuli were preceded by
      clicks (thus timed 'fast') and the standards were presented without clicks (thus
      timed 'normally'); in another condition the clicks preceded the standards but not
      the comparisons. The psychophysical function obtained from the bisection
      procedure shifted in opposite directions with the different manipulations,
      consistent with both relative 'speeding up' and 'slowing down' of the pacemaker
      of the internal clock. 

PMID- 24925500
TI  - Prey-handling behaviour of Octopus vulgaris (Mollusca, Cephalopoda) on Bivalve
      preys.
AB  - This study examines the ability of Octopus vulgaris to prey on bivalve molluscs
      showing that octopuses exhibited the same behavioural pattern irrespective of the
      prey species. When the initial pulling method did not result efficient octopuses
      skipped to drilling accompanied by an increase in the handling time. A complete
      behavioural repertoire of O. vulgaris in handling bivalve preys is also given. 

PMID- 24925501
TI  - Discounting of delayed rewards across the life span: age differences in
      individual discounting functions.
AB  - The present effort addressed both the issue of the generality of choice models
      and the issue of possible qualitative developmental change in temporal
      discounting by examining behavior at the individual level across the life span.
      Data from individual children, young adults, and older adults who participated in
      two previous studies were analyzed [Green, L., Fry, A.F., Myerson, J., 1994.
      Discounting of delayed rewards: a life-span comparison. Psychol. Sci. 5, 33-36;
      Green, L., Myerson, J., Lichtman, D., Rosen, S., Fry, A., 1996. Temporal
      discounting in choice between delayed rewards: the role of age and income.
      Psychol. Aging 11, 79-84]. At all ages, a hyperbola-like function originally
      proposed by Green et al. (1994) based on group data, provided the best
      description of individual discounting functions. Two developmental trends were
      observed. The rate at which individuals discounted the value of delayed rewards
      decreased with age, and there was a systematic change in the shape of the
      discounting function. Each of these trends was reflected in a separate parameter
      of the model. The fact that the same mathematical model described the behavior of
      individuals of different ages suggests that age and individual differences in the
      discounting of delayed rewards are primarily quantitative in nature and reflect
      variations on fundamentally similar choice processes. 

PMID- 24925502
TI  - Conditioning pigeons to discriminate naturally lit insect specimens.
AB  - Pigeons (Columba livia) were trained on a visual discrimination task using a
      novel apparatus which enabled pinned specimens of insects, illuminated by natural
      daylight, to be presented under a pecking key transparent to ultraviolet light.
      Three birds showed evidence of learning to discriminate between sets of wasp and
      fly specimens. This response transferred to specimens of four hoverfly species,
      the strength of the response varying between the different hoverfly species. This
      conditioning technique offers a promising means of analysing mechanisms of visual
      processing in birds that are relevant to theories of the evolution of camouflage
      and mimicry. 

PMID- 24925503
TI  - Stereotactic radiosurgery for acromegaly: outcomes by adenoma subtype.
AB  - PURPOSE: The subtypes of somatotroph-cell pituitary adenomas have been correlated
      with clinical and histopathological variables. Densely granulated somatotroph
      cell (DG) adenomas are typically highly responsive to somatostatin analog drugs,
      whereas sparsely granulated somatotroph-cell (SG) are less responsive. The aim of
      the study is to determine the effect of stereotactic radiosurgery (SRS) on
      remission and development of new pituitary deficiency according to the different
      subtypes of growth hormone (GH) secreting adenomas. METHODS: A total of 176
      patients underwent SRS for acromegaly at the University of Virginia. Diagnosis of
      acromegaly was based on the combination of clinical features and biochemical
      assessment including the serum GH level, and age- and gender-matched serum
      insulin-like growth factor-1 level. All patients underwent endocrine and neuro
      imaging evaluations before and after SRS. Histological specimens were available
      in 73 patients. RESULTS: The histopathological examination showed 34 patients had
      a DG adenoma, 19 had a SG adenoma, eight had a mixed DG/SG pattern, while other
      rare mixed subtypes were present in 12 patients. Patients who had a SG adenoma
      were more likely to be younger and female, and the SG adenomas appeared to be
      more invasive into the cavernous sinus. With a median follow-up of 67 months
      (range 6-188 months), 55/73 patients (75.3%) achieved remission. The median time
      to remission was 26 months (range 6-102 months). The actuarial remission rates in
      the DG adenoma group at 2, 4, and 6 years post-radiosurgery were 35.1, 71.4, and
      79.3%, respectively, while those in SG adenoma group were 35.4, 73.1, and 82.1%,
      respectively. CONCLUSION: While patients who had a SG adenoma may be less
      responsive to medical therapy, they exhibited similar responses to SRS as
      patients with a DG adenoma. For SG adenomas, which respond less well to medical
      therapy, earlier SRS may be reasonable for consideration.

PMID- 24925504
TI  - Shielding Parenteral Nutrition Solutions From Light: A Randomized Controlled
      Trial.
AB  - INTRODUCTION: Oxidant stress is implicated in the pathogenesis of
      bronchopulmonary dysplasia (BPD). Light induces peroxide generation in parenteral
      nutrition (PN) solutions, creating an oxidant stress. Shielding PN from light
      decreases its peroxide content, which has nutrition and biochemical benefits in
      animals and humans. This study aims at determining whether full light protection
      of PN decreases the rate of bronchopulmonary dysplasia and/or death in very low
      birth-weight infants. METHODS: Multicenter randomized controlled trial of
      photoprotection, using amber bags and tubing initiated during compounding of PN
      and maintained throughout infusion in the light-protected (LP) group. The control
      group (light exposed [LE]) received PN exposed to ambient light. Depending on
      centers, lipids were infused either separately or as all-in-one PN. RESULTS: In
      total, 590 infants born <30 weeks gestational age were included. At
      randomization, LE and LP groups did not differ clinically except for maximal FiO2
      before 12 hours. The rate of BPD/death was not different between groups at 28
      days (77% LP vs 72% LE, P = .16) or at 36 weeks corrected age (30% LP vs 27% LE,
      P = .55). Multivariate analysis showed no significant effect of photoprotection
      on BPD and/or death. The rate of BPD/death was significantly lower (odds ratio,
      0.54; 95% confidence interval, 0.32-0.93; P = .02) in infants receiving all-in
      one PN vs those who received lipids separately. CONCLUSION: This study did not
      show significant beneficial effects of photoprotection. Since the decreased rate
      of BPD/death found with all-in-one PN relates to a center-dependent variable,
      this warrants further investigation.

PMID- 24925505
TI  - Public funding and private investment for R&D: a survey in China's pharmaceutical
      industry.
AB  - BACKGROUND: In recent years, China has experienced tremendous growth in its
      pharmaceutical industry. Both the Chinese government and private investors are
      motivated to invest into pharmaceutical research and development (R&D). However,
      studies regarding the different behaviors of public and private investment in
      pharmaceutical R&D are scarce. Therefore, this paper aims to investigate the
      current situation of public funding and private investment into Chinese
      pharmaceutical R&D. METHODS: The primary data used in the research were obtained
      from the China High-tech Industry Statistics Yearbook (2002-2012) and China
      Statistical Yearbook of Science and Technology (2002-2012). We analyzed public
      funding and private investment in five aspects: total investment in the industry,
      funding sources of the whole industry, differences between provinces, difference
      in subsectors, and private equity/venture capital investment. RESULTS: The vast
      majority of R&D investment was from private sources. There is a significantly
      positive correlation between public funding and private investment in different
      provinces of China. However, public funding was likely to be invested into less
      developed provinces with abundant natural herbal resources. Compared with the
      chemical medicine subsector, traditional Chinese medicine and biopharmaceutical
      subsectors obtained more public funding. Further, the effect of the government
      was focused on private equity and venture capital investment although private
      fund is the mainstream of this type of investment. CONCLUSIONS: Public funding
      and private investment play different but complementary roles in pharmaceutical
      R&D in China. While being less than private investment, public funding shows its
      significance in R&D investment. With rapid growth of the industry, the
      pharmaceutical R&D investment in China is expected to increase steadily from both
      public and private sources.

PMID- 24925506
TI  - The date of antler casting, age and social hierarchy relationships in the red
      deer stag.
AB  - A five-year observation of social interactions and the antler cycle of the stag
      was performed in the "white" red deer population in the Zehusice game reserve,
      Czechoslovakia. The results indicate that the antler casting time of individual
      stags was dependent primarily on social status and that the influence of age was
      of secondary importance. The more dominant the stag, the earlier antler casting
      occurred. The stags of higher social status also tended to shed velvet earlier,
      although this relationship was not significant. The hormonal regulation of the
      antler cycle relating to social hierarchy is discussed. 

PMID- 24925507
TI  - Acquisition and extinction of gustatory aversion in two lines of rats selectively
      bred for differential shuttlebox avoidance performance.
AB  - Consumption of a palatable saccharin-glucose (SG) solution was compared in Roman
      High Avoidance (RHA/Verh) and Roman Low Avoidance (RLA/Verh) lines of rats in a
      taste aversion acquisition and extinction paradigm. Prior to treatment, SG-intake
      in a 1 -h drinking test by RHA/Verh rats was much greater than that by RLA/Verh
      rats. Both psychogenetic lines increased SG-intake over a series of exposures
      when each presentation was followed by saline injection, but decreased SG-intake
      when each presentation was followed by apomorphine injection. At the end of the
      acquisition phase, RHA/Verh rats treated with a toxic dose of apomorphine drank
      36% less SG than RHA/Verh rats that were injected with saline, whereas RLA/Verh
      rats treated with apomorphine consumed 54% less SG than RLA/Verh rats injected
      with saline. Following 16 daily presentations of SG but no injections, extinction
      of the conditioned gustatory aversion was complete in the RHA/Verh group
      previously treated with apomorphine, but it remained incomplete in the RLA/Verh
      rats previously treated with apomorphine. This stronger taste aversion exhibited
      by RLA/Verh rats is in marked contrast to their extremely inferior performance in
      a shuttlebox active avoidance task. The basis of the behavioral differences in
      these two psychogenetically selected lines of rats is discussed. 

PMID- 24925508
TI  - Long-term effects of testosterone injections on the social behaviour of male
      ducks and their physiological correlates.
AB  - During three independent experiments, we demonstrated that repeated injections of
      testosterone propionate (TP) induce, after the termination of treatment, a strong
      inhibition of social displays in intact male domestic ducks. This behavioural
      inhibition may last for several months and appears relatively specific, as sexual
      behaviour was generally normal in the previously injected birds. This effect is
      probably not directly related to the neonatal differentiation of the brain, as it
      can be induced by injections given when the birds are already several months old.
      The inhibition of social displays is not paralleled by drastic changes in the
      plasma levels of pituitary-gonadal hormones (testosterone, follicle stimulating
      hormone and luteinizing hormone), and thus is not explained by the lack of
      endogenous testosterone. It is postulated that the behavioural inhibition results
      from a decreased sensitivity to testosterone of the neural mechanisms involved in
      the control of displays, and possible mechanisms explaining this decreased
      sensitivity at the biochemical level are briefly reviewed. 

PMID- 24925509
TI  - Agonistic behavior, the development of the social hierarchy and stress in
      genetically diverse flocks of chickens.
AB  - The agonistic behavior and development of the social hierarchy of juvenile
      pullets were studied in two lines of chickens which had been divergently selected
      for juvenile body weight and in which the dwarf gene (dw) was segregating. The
      lines differed significantly in both the frequency and intensity of agonistic
      encounters. Dwarf and normal genotypes differed in the frequency of encounters in
      both lines, whereas for the intensity of encounters, the difference was only in
      the high weight line. Although the frequency was more important than the
      intensity of encounters in determining social rank, agonistic behaviors accounted
      for only 20% of the variation in rank. The stability of the social orders
      increased slightly between 6 and 10 weeks of age. Although the correlations
      between behavioral and physiological variables agreed in sign with those
      predicted of stressors, their values were low. Therefore, it was concluded that
      the pullets were only minimally stressed by normal agonistic activity during the
      development of the social hierarchy. 

PMID- 24925510
TI  - Observational learning in Japanese quail.
AB  - In spite of interest in the cultural transmission of animal behaviour,
      observational learning has not previously been demonstrated in Japanese quail. In
      the present experiment three groups of 10 quail were trained to peck for
      reinforcement under discriminative stimulus control. The group which was allowed
      to observe performance of skilled companions learned faster than a group
      observing no-pecking models and a group learning without observational
      experience. Furthermore, observation of no-pecking models can inhibit learning. A
      sensory-sensory conditioning model can account for the results. 

PMID- 24925515
TI  - Letter to the editor.

PMID- 24925511
TI  - Sensitivity, range and temperature dependence of hearing in the grass frog and
      fire-bellied toad.
AB  - Multi-unit recordings from the torus semicircularis of the fire-bellied toad
      (Bombina bombina L.) and the grass frog (Rana t. temporaria L.) were used to
      obtain threshold vs. frequency curves for these anurans. The effect of body
      temperature on these audiograms was tested over a range of 10-28 degrees  C for
      the toad and 5-20 degrees  C for the frog. The range of frequencies audible to
      the fire-bellied toad at a body temperature of 21 degrees  C extends to 2400-3000
      Hz. Threshold is relatively low in three regions: 300-450 Hz, 700-900 Hz and 1200
      1700 Hz. The auditory system is most sensitive in the low frequency region. The
      audiograms of both species depend greatly on temperature. As temperature is
      increased sensitivity is enhanced, particularly at low and intermediate
      frequencies. Grass frogs are maximally sensitive at temperatures as low as 15
      degrees  C, whereas the auditory threshold of fire-bellied toads continue to fall
      as the temperature is raised from 16 degrees  C to 22 degrees  C. Hearing
      evidently is adapted to different temperature ranges in the two species, and
      these correspond to the temperatures at which the animals engage in mating
      behavior. 

PMID- 24925516
TI  - Triggers to offering bariatric surgery in  the management of type 2 diabetes.
AB  - It is unclear how current guidelines suggesting bariatric surgery as a
      therapeutic option for management of obesity complicated by type 2 diabetes
      mellitus are utilised in clinical practice. Of 609 patients with T2DM assessed in
      this study, 147 had a BMI >= 35 kg/m2; and of these 147, patients where bariatric
      surgery had been discussed as compared to those where it had not been discussed,
      had a higher BMI (44.4 +/- 6.8 kg/m2 versus 40.3 +/- 5.2 kg/m2, p < 0.005).
      Diabetes related factors did not differ between the two groups.

PMID- 24925517
TI  - Clinical and demographic risk factors associated with mortality during early
      adulthood in a population-based cohort of childhood-onset type 1 diabetes.
AB  - AIMS: To calculate standardized mortality ratios and to assess the association
      between paediatric clinical factors and higher risk of mortality during early
      adulthood in a population-based cohort of subjects with Type 1 diabetes. METHODS:
      Subjects with Type 1 diabetes were identified through the Western Australian
      Children's Diabetes Database and clinical data for those who reached 18 years of
      age (n = 1309) were extracted. An age- and sex-matched (without diabetes)
      comparison cohort (n = 6451) was obtained from the birth registry. Mortality
      records were obtained from the death registry. Participants were followed up
      until 31 January 2012. Associations of clinical factors (from clinic visits
      before 18 years of age) with mortality were assessed using Cox proportional
      hazard models. RESULTS: The standardized mortality ratio for all-cause mortality
      was 1.7 (95% CI 0.7-3.3) for male and 10.1 (95% CI 5.2-17.7) for female subjects
      with Type 1 diabetes (median age at end of study 25.6 years). The adjusted hazard
      ratio was 1.5 (95% CI 1.1-2.1) for a 1% increase in mean paediatric HbA1c level,
      3.8 (95% CI 0.9-15.3) for four episodes of severe hypoglycaemia relative to zero
      episodes, and 6.21 (95% CI 1.4-28.4) for a low-level socio-economic background
      relative to a high-level background. CONCLUSIONS: People with childhood-onset
      Type 1 diabetes have higher mortality rates in early adulthood. At particularly
      high risk are women, those with a history of poor HbA1c levels, those with
      recurrent severe hypoglycaemia during paediatric management, and those from a low
      socio-economic background. These groups may benefit from intensified management
      during transition from paediatric to adult care facilities.

PMID- 24925518
TI  - Ion pairing in protic ionic liquids probed by far-infrared spectroscopy: effects
      of solvent polarity and temperature.
AB  - The cation-anion and cation-solvent interactions in solutions of the protic ionic
      liquid (PIL) [Et3NH][I] dissolved in solvents of different polarities are studied
      by means of far infrared vibrational (FIR) spectroscopy and density functional
      theory (DFT) calculations. The dissociation of contact ion pairs (CIPs) and the
      resulting formation of solvent-separated ion pairs (SIPs) can be observed and
      analyzed as a function of solvent concentration, solvent polarity, and
      temperature. In apolar environments, the CIPs dominate for all solvent
      concentrations and temperatures. At high concentrations of polar solvents, SIPs
      are favored over CIPs. For these PIL/solvent mixtures, CIPs are reformed by
      increasing the temperature due to the reduced polarity of the solvent. Overall,
      this approach provides equilibrium constants, free energies, enthalpies, and
      entropies for ion-pair formation in trialkylammonium-containing PILs. These
      results have important implications for the understanding of solvation chemistry
      and the reactivity of ionic liquids.

PMID- 24925519
TI  - Synthesis and evaluation of a new series of 3,5-bis((5-bromo-6-methyl-2-t
      aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their cyclized products
      'pyrimidinylthio pyrimidotriazolothiadiazines' as 15- lipo-oxygenase inhibitors.
AB  - A series of new 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4
      triazol-4-amines and their cyclized products 'pyrimidinylthio
      pyrimidotriazolothiadiazines' were designed, synthesized, and evaluated as
      potential inhibitors of 15-lipo-oxygenase (15-LO). Their syntheses started by
      initial condensation of 2:1 equivalents of pyrimidine with triazole and
      subsequent nucleophilic displacement of the chlorine atoms with secondary amines
      and finally cyclocondensation in the presence of NaNH2. The compounds 4d and 4f
      showed the best IC50 of 15-LO inhibition (IC50 = 9 and 12 MUm, respectively).
      Compounds 4a-g were docked into 15-LO. We suggest that the hydrogen bonds in
      quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play
      major role in lipo-oxygenase inhibition by this set of synthesized analogs and
      hydrophobic nature of this protein's binding site should be considered in ongoing
      investigations.

PMID- 24925520
TI  - Combined therapy with insulin and growth hormone in 17 patients with type-1
      diabetes and growth disorders.
AB  - BACKGROUND/AIM: Combined growth hormone (GH) and insulin therapy is rarely
      prescribed by pediatric endocrinologists. We investigated the attitude of Italian
      physicians to prescribing that therapy in the case of short stature and type-1
      diabetes (T1DM). METHODS: A questionnaire was sent and if a patient was
      identified, data on growth and diabetes management were collected. RESULTS: Data
      from 42 centers (84%) were obtained. Of these, 29 centers reported that the use
      of combined therapy was usually avoided. A total of 17 patients were treated in
      13 centers (GH was started before T1DM onset in 9 patients and after the onset of
      T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by
      GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH
      was added subsequently, mean insulin dose increased during the first 6 months of
      therapy from 0.7 +/- 0.2 to 1.0 +/- 0.2 U/kg (p = 0.004). HbA1c was unchanged
      during the first 6 months of combined therapy. CONCLUSIONS: Most Italian
      physicians do not consider prescribing the combined GH-insulin therapy in
      diabetic children with growth problems. However, the results of the 17 patients
      identified would confirm that the combined therapy was feasible and only caused
      mild insulin resistance. GH therapy was effective in promoting growth in most
      patients and did not affect diabetes metabolic control.

PMID- 24925521
TI  - Turning the page.

PMID- 24925523
TI  - Postoperative courses of breast reconstruction using inferior adipofascial tissue
      repair.
AB  - BACKGROUND: Nevertheless in breast conserving surgery, the dissection of inferior
      part of breast mound will cause severe deformity, which affects the patient's
      quality of life adversely. We have used an infra-mammary adipofascial tissue to
      repair the defect, and breast mound could be reconstructed concurrently in
      primary breast cancer surgery. PATIENTS AND SURGICAL PROCEDURE: From September
      2009 to June 2012, we performed the infra-mammary adipofascial tissue repair
      (IATR) on 25 patients with breast cancer in inferior site of their breast mound.
      Surgeon makes the skin incision on the infra-mammary line and performs the
      quadrantectomy as planned. After verifying its negative surgical margin
      pathologically, we mobilize the adipofascial fat tissue associated with myofascia
      of the serratus anterior muscle from the infra-mammary area. This tongue-shaped
      flap is reflected back, and fills the defect of breast mound. We performed
      routinely examination, mammography, and ultra-sound echogram to the IATR patients
      who visited our hospital after 1 year from the end of treatment. We, furthermore,
      performed the QOL questionnaire (QOL-ACD and QOL-ACD-B) to them and
      retrospectively compared their data to that from the other breast surgery
      patients. RESULTS: All patients with IATR were treated with irradiation, and no
      image findings of a partial or total necrosis of the flap recognized 1 year after
      examination. They produced good cosmetic results; however, they could not elevate
      the QOL score on the whole.

PMID- 24925522
TI  - Biological variability in serum anti-Mullerian hormone throughout the menstrual
      cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women.
AB  - STUDY QUESTION: Does serum anti-Mullerian hormone (AMH) vary significantly
      throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy
      premenopausal women? SUMMARY ANSWER: Serum AMH levels vary statistically
      significantly across the menstrual cycle in both ovulatory and sporadic
      anovulatory cycles of healthy eumenorrheic women. WHAT IS KNOWN ALREADY: Studies
      to date evaluating serum AMH levels throughout the menstrual cycle have
      conflicting results regarding intra-woman cyclicity. No previous studies have
      evaluated an association between AMH and sporadic anovulation. STUDY DESIGN,
      SIZE, DURATION: We conducted a prospective cohort study of 259 regularly
      menstruating women recruited between 2005 and 2007. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Women aged 18-44 years were followed for one (n = 9) or two (n
      = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak
      progesterone concentration <=5 ng/ml and no serum LH peak on the mid or late
      luteal visits. Serum AMH was measured at up to eight-time points throughout each
      cycle. MAIN RESULTS AND THE ROLE OF CHANCE: Geometric mean AMH levels were
      observed to vary across the menstrual cycle (P < 0.01) with the highest levels
      observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the
      time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular
      versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid
      follicular versus late luteal, P = 0.05). Patterns were similar across all age
      groups and during ovulatory and anovulatory cycles, with higher levels of AMH
      observed among women with one or more anovulatory cycles (P = 0.03). LIMITATIONS,
      REASONS FOR CAUTION: Ovulatory status was not verified by direct visualization.
      AMH was analyzed using the original Generation II enzymatically amplified two
      site immunoassay, which has been shown to be susceptible to assay interference.
      Thus, absolute levels should be interpreted with caution, however, patterns and
      associations remain consistent and any potential bias would be non-differential.
      WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates a significant
      variation in serum AMH levels across the menstrual cycle regardless of ovulatory
      status. This variability, although statistically significant, is not large enough
      to warrant a change in current clinical practice to time AMH measurements to
      cycle day/phase. STUDY FUNDING/COMPETING INTERESTS: This research was supported
      by the Intramural Research Program of the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development (NICHD), National Institutes of
      Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1
      HHSN27500001). The authors have no conflicts of interest to declare.

PMID- 24925524
TI  - Is clinical breast examination effective in Japan? Consideration from the age
      specific performance of breast cancer screening combining mammography with
      clinical breast examination.
AB  - BACKGROUND: There is controversy about the value of clinical breast examination
      (CBE) in breast cancer screening programs that include mammography. METHODS: In
      Fukui Prefecture, a screening combining mammography with CBE was employed on
      62,447 women from 2004 to 2009. We examined the sensitivity and specificity of
      mammography alone, and mammography and CBE together for each age group (40-49, 50
      59, 60-69, and 70-79). RESULTS: 167 breast cancers and 49 false-negative cancers
      were detected during 5 years. For the combined screening, the sensitivities were
      73.1, 74.1, 78.3, and 86.5 %, and the specificities were 83.8, 87.5, 89.8, and
      90.9 % in the groups of 40-49, 50-59, 60-69, and 70-79 years, respectively. In
      the mammography-specific analysis, sensitivity decreased to 69.8 % (-3.3 %), 66.7
      % (-7.7 %), 77.3 % (-1.0 %), and 83.8 % (-2.7 %) in the groups of 40-49, 50-59,
      60-69, and 70-79 years, respectively. There were greater reductions in the groups
      of 40-49 and 50-59 years than in those of 60-69 and 70-79 years, but there was no
      statistically significant decrease. Specificity generally increased with
      increasing age and there was a significant improvement in specificity among all
      age groups, except that of 70-79 years. CONCLUSIONS: Our findings suggest that
      there is a trade-off between sensitivity and specificity associated with CBE
      added to mammography. This tendency is greater in those 40-50 years of age than
      in those 60-70 years of age. We consider that CBE may be omitted from breast
      cancer screening among women aged 60 and 70 years. Furthermore, another modality
      to complement mammography screening in younger Japanese women is expected.

PMID- 24925525
TI  - Vascular endothelial dysfunction and nutritional compounds in early type 1
      diabetes.
AB  - Cardiovascular disease is the major cause of death in patients with type 1
      diabetes. Vascular endothelial dysfunction is an early pathophysiological
      precursor of cardiovascular disease. There is extensive evidence that
      hyperglycemia causes acute perturbations in endothelial function likely due to
      increases in oxidative damage. Interestingly, oscillating hyperglycemia may cause
      more damage than persistent hyperglycemia. Many, but not all, studies indicate
      that vascular endothelial dysfunction occurs early in the course of type 1
      diabetes and is present even in adolescents. Ascorbic acid has been shown to
      diminish the acute effects of hyperglycemia on endothelial function in type 1
      diabetes and in conjunction with euglycemia to restore endothelial function to
      normal values in adults with well-controlled diabetes. In vitro and in vivo
      animal evidence suggests potential benefit from two other small molecule
      antioxidants, nicotinamide and taurine. Early studies suggested that folate
      supplementation may improve endothelial function in adolescents with type 1
      diabetes but this has not been confirmed by more recent studies. Epidemiological
      evidence suggests a possible role for vitamin D therapy although intervention
      studies in type 2 diabetes have yielded varying results and have not been done in
      type 1 diabetes. Further exploration of these and other compounds is clearly
      appropriate if we are to reduce cardiovascular risk in type 1 diabetes. 

PMID- 24925526
TI  - Endothelium-derived hyperpolarizing factor mediates bradykinin-stimulated tissue
      plasminogen activator release in humans.
AB  - AIMS: Bradykinin (BK) stimulates tissue plasminogen activator (t-PA) release from
      human endothelium. Although BK stimulates both nitric oxide and endothelium
      derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release
      remains unexplored. This study sought to determine the mechanisms of BK
      stimulated t-PA release in the forearm vasculature of healthy human subjects.
      METHODS: In 33 healthy subjects (age 40.3 +/- 1.9 years), forearm blood flow
      (FBF) and t-PA release were measured at rest and after intra-arterial infusions
      of BK (400 ng/min) and sodium nitroprusside (3.2 mg/min). Measurements were
      repeated after intra-arterial infusion of tetraethylammonium chloride (TEA; 1
      umol/min), fluconazole (0.4 umol.min(-1).l(-1)), and N(G)-monomethyl-L-arginine
      (L-NMMA, 8 umol/min) to block nitric oxide, and their combination in separate
      studies. RESULTS: BK significantly increased net t-PA release across the forearm
      (p < 0.0001). Fluconazole attenuated both BK-mediated vasodilation (-23.3 +/-
      2.7% FBF, p < 0.0001) and t-PA release (from 50.9 +/- 9.0 to 21.3 +/- 8.9
      ng/min/100 ml, p = 0.02). TEA attenuated FBF (-14.7 +/- 3.2%, p = 0.002) and
      abolished BK-stimulated t-PA release (from 22.9 +/- 5.7 to -0.8 +/- 3.6
      ng/min/100 ml, p = 0.0002). L-NMMA attenuated FBF (p < 0.0001), but did not
      inhibit BK-induced t-PA release (nonsignificant). CONCLUSION: BK-stimulated t-PA
      release is partly due to cytochrome P450-derived epoxides and is inhibited by
      K(+)Ca channel blockade. Thus, BK stimulates both EDHF-dependent vasodilation and
      t-PA release.

PMID- 24925527
TI  - p62/SQSTM1 plays a protective role in oxidative injury of steatotic liver in a
      mouse hepatectomy model.
AB  - AIMS: Liver injury and regeneration involve complicated processes and are
      affected by various physio-pathological factors. We investigated the mechanisms
      of steatosis-associated liver injury and delayed regeneration in a mouse model of
      partial hepatectomy. RESULTS: Initial regeneration of the steatotic liver was
      significantly delayed after hepatectomy. Although hepatocyte proliferation was
      not significantly suppressed, severe liver injury with oxidative stress (OS)
      occurred immediately after hepatectomy in the steatotic liver. Fas-ligand
      (FasL)/Fas expression was upregulated in the steatotic liver, whereas the
      expression of antioxidant and anti-apoptotic molecules (catalase/MnSOD/Ref-1 and
      Bcl-2/Bcl-xL/FLIP, respectively) and p62/SQSTM1, a steatosis-associated protein,
      was downregulated. Interestingly, pro-survival Akt was not activated in response
      to hepatectomy, although it was sufficiently expressed even before hepatectomy.
      Suppression of p62/SQSTM1 increased FasL/Fas expression and reduced nuclear
      factor erythroid 2-related factor-2 (Nrf-2)-dependent antioxidant response
      elements activity and antioxidant responses in steatotic and nonsteatotic
      hepatocytes. Exogenously added FasL induced severe cellular OS and
      necrosis/apoptosis in steatotic hepatocytes, with only the necrosis being
      inhibited by pretreatment with antioxidants, suggesting that FasL/Fas-induced OS
      mainly leads to necrosis. Furthermore, p62/SQSTM1 re-expression in the steatotic
      liver markedly reduced liver injury and improved liver regeneration. INNOVATION:
      This study is the first which demonstrates that reduced expression of p62/SQSTM1
      plays a crucial role in posthepatectomy acute injury and delayed regeneration of
      steatotic liver, mainly via redox-dependent mechanisms. CONCLUSION: In the
      steatotic liver, reduced expression of p62/SQSTM1 induced FasL/Fas overexpression
      and suppressed antioxidant genes, mainly through Nrf-2 inactivation, which, along
      with the hypo-responsiveness of Akt, caused posthepatectomy necrotic/apoptotic
      liver injury and delayed regeneration, both mainly via a redox-dependent
      mechanism.

PMID- 24925528
TI  - Activation of nuclear factor kappaB pathway and downstream targets survivin and
      livin by SHARPIN contributes to the progression and metastasis of prostate
      cancer.
AB  - BACKGROUND: Nuclear factor kappaB (NFkappaB) signaling is strongly associated
      with tumor progression, and studies have shown that SHANK-associated RH domain
      interacting protein (SHARPIN) is crucial for NFkappaB pathway activation.
      However, the expression and functions of SHARPIN in prostate cancer (PCa) have
      not yet been defined. METHODS: The expression of SHARPIN in PCa cell lines and
      tissues was evaluated with western blotting, quantitative real-time polymerase
      chain reaction, and immunohistochemistry. After SHARPIN was silenced in the PCa
      cell lines, western blots were used to confirm that SHARPIN physically associated
      with components of the NFkappaB pathway and the downstream targets (survivin and
      livin). The functions of SHARPIN in cell proliferation, migration, and invasion
      in vitro were measured with 5-(3-carboxymethoxyphenyl)-2-(4,5-dimenthylthiazoly)
      3-(4-sulfophenyl)tetrazolium, inner salt (MTS), Transwell, and invasion assays,
      respectively. Flow cytometry was employed to evaluate cell apoptosis.
      Furthermore, tumorigenesis in vivo was examined with tumorigenicity assays.
      RESULTS: SHARPIN expression was upregulated in PCa cell lines and tissues. The
      knockdown of SHARPIN or incubation with Bay 11-7082 (an NFkappaB inhibitor) led
      to dramatically decreased levels of phosphorylated IkappaBalpha and
      phosphorylated p65 in comparison with the control group. Downregulation of
      survivin and livin due to SHARPIN inhibition was attributable to transcriptional
      repression (P < .05). Decreases in cell viability, migration, invasion, and
      survival with a higher sensitivity to docetaxel in vitro and with repressed
      tumorigenesis in vivo were observed upon SHARPIN silencing, and this was
      consistent with the results from inhibition of the NFkappaB pathway and its
      downstream targets. CONCLUSION: The current study demonstrates that
      overexpression of SHARPIN promotes activation of the NFkappaB pathway and
      downstream targets survivin and livin, which potentially contributes to PCa
      development.

PMID- 24925529
TI  - Antibiotic resistance and the environment--there and back again: Science &
      Society series on Science and Drugs.

PMID- 24925530
TI  - Tpz1TPP1 SUMOylation reveals evolutionary conservation of SUMO-dependent Stn1
      telomere association.
AB  - Elongation of the telomeric overhang by telomerase is counteracted by synthesis
      of the complementary strand by the CST complex, CTC1(Cdc13)/Stn1/Ten1.
      Interaction of budding yeast Stn1 with overhang-binding Cdc13 is increased by
      Cdc13 SUMOylation. Human and fission yeast CST instead interact with overhang
      binding TPP1/POT1. We show that the fission yeast TPP1 ortholog, Tpz1, is
      SUMOylated. Tpz1 SUMOylation restricts telomere elongation and promotes Stn1/Ten1
      telomere association, and a SUMO-Tpz1 fusion protein has increased affinity for
      Stn1. Our data suggest that SUMO inhibits telomerase through stimulation of
      Stn1/Ten1 action by Tpz1, highlighting the evolutionary conservation of the
      regulation of CST function by SUMOylation. 

PMID- 24925531
TI  - Penetrating foreign body in the nasal floor through nasolacrimal duct.
AB  - Clinical otolaryngologists frequently encounter nasal foreign bodies (FBs)
      particularly among children. The removal of nasal FBs is a common
      otolaryngological practice. However, occasionally trauma results from FBs being
      lodged in the nasal cavity especially through the nasolacrimal duct. In this
      article we present an unusual case of a FB that from the left medial canthus went
      inside the nasolacrimal duct, then through the inferior turbinate and stuck in
      the floor of the nose. We describe the transnasal endoscopic approach used and we
      recommend that the treatment be done as soon as possible to avoid complications. 

PMID- 24925532
TI  - Primary tuberculosis of the palate.
AB  - Tuberculosis (TB) is a life-threatening infectious disease with a high world
      incidence. However, TB with oral expression is considered rare. The importance of
      recognising this entity lies in its early diagnosis and treatment, as it can be
      easily confused with neoplastic or traumatic ulcers. We present a case of a
      primary TB located in the hard palate and gingiva in an 88-year-old woman. 

PMID- 24925533
TI  - Basal cell adenocarcinoma of the parotid gland detected in a patient with breast
      cancer.
AB  - Basal cell adenocarcinoma (BCAC) is a rare tumour of the salivary glands and
      often associated with a good prognosis. The present case had BCAC of the parotid
      gland as the second primary tumour in addition to breast cancer. The patient was
      a 66-year-old woman who underwent mastectomy due to breast cancer. She then
      underwent adjuvant chemotherapy and adjuvant hormone therapy. After 4 years of
      disease-free follow-up, the patient presented with a swelling on the left cheek.
      The examination of the biopsy specimen revealed BCAC of the parotid gland. The
      patient then underwent left parathyroidectomy plus left neck dissection. Adjuvant
      radiotherapy was performed. Despite the therapy, the patient developed four local
      recurrences within 1 year, and then developed metastasis to the pleura. A
      swelling in the parotid gland in a patient with breast cancer should be carefully
      screened for the presence of a second primary tumour.

PMID- 24925534
TI  - Gastroduodenal artery aneurysm.

PMID- 24925535
TI  - Spontaneous bladder perforation unrelated to trauma or surgery.
AB  - Urinary bladder ruptures (UBR) typically result from either blunt or penetrating
      trauma, or from iatrogenic surgical injuries. Patients typically present with
      symptoms including lower abdominal pain, haematuria, dysuria and anuria. Here, we
      report on a rare case of spontaneous bladder perforation. A 60-year-old,
      Caucasian woman initially presented with lower abdominal pain and diarrhoea, and
      was subsequently found to have an elevated serum creatinine level. A CT cystogram
      revealed a leak from the bladder. The patient consented to exploratory laparotomy
      and repair of the non-traumatic bladder perforation. At the time of the last
      follow-up, given the fact that the patient's urodynamics were unremarkable and
      that she was emptying her bladder well (repeat postvoid residual was zero), the
      patient was informed that she did not require future urological follow-up unless
      difficulties arise. 

PMID- 24925536
TI  - Delayed presentation of an undiscovered nasopharyngeal foreign body.
AB  - Suspected paediatric aerodigestive tract foreign body (FB) ingestion or
      aspiration is a commonly encountered emergency. Management may require a general
      anaesthetic for retrieval with bronchoscopy, laryngoscopy and oesophagoscopy,
      each dependent on the history and investigations of the case in question. We
      describe the case of a foreign body, which was missed in the nasopharynx for more
      than 3 years and also discuss how pressures on National Health Service (NHS)
      referral and follow-up patterns may have altered the time course of the eventual
      discovery.

PMID- 24925537
TI  - Aromatase inhibition in relapsing low malignant potential serous tumours of the
      ovary.
AB  - Low malignant potential serous tumours (LMPSTs) of the ovary represent an
      indolent disease, with an excellent prognosis in a majority of patients. Patients
      with recurrent LMPSTs tend to develop widespread disease with a mortality rate as
      high as 70%. These tumours tend to have a very poor response to standard
      chemotherapy, and the management of primary and recurrent disease beyond surgical
      resection is not well defined. The majority of LMPST have been reported to
      express oestrogen and progesterone hormone receptors. However, only three
      reported cases of antihormonal treatment in this setting, and only one using
      aromatase inhibitors (AI), have been previously reported. We herein report long
      term complete remission of two patients with relapsed, chemotherapy-resistant
      LMPSTs, treated with long-term AI (anastrozole 1 mg daily) as per negative MRI
      and positron emission tomography scans. Our results warrant further investigation
      for the use of AIs for metastatic recurrent LMPSTs.

PMID- 24925538
TI  - Aphasia due to isolated infarction of the corpus callosum.
AB  - A 63-year-old man with an isolated infarction of the corpus callosum developed
      expressive aphasia in addition to the deficits traditionally associated with a
      disconnection syndrome. 

PMID- 24925539
TI  - Transrectal impalement of an incense stick in a child presenting as foreign body
      in the urinary bladder.
AB  - The diversity of objects that can be found in the urinary bladder often surpasses
      the urologist's imagination and mostly they are introduced per urethrally.
      Impalement injuries of the rectum with bladder perforation have been rarely
      reported. A high index of clinical suspicion is required to make the diagnosis of
      bladder perforation while assessing patients presenting with rectal impalement.
      In this interesting case, a young male child presented with haematuria and
      dysuria. He had a history of accidentally sitting on an agarbatti (Indian incense
      stick) stand while playing, followed by perianal pain which subsided
      spontaneously. Next day he presented with haematuria and dysuria. Clinical
      examination was inconclusive. On thorough investigation, a linear echogenic
      foreign body was found in the urinary bladder. The child was operated and the
      foreign body (incense stick) was removed. This is the first reported case of
      rectal impalement injury with incense stick, migrated to the urinary bladder in a
      2-year-old child. 

PMID- 24925540
TI  - Pneumococcal vaccine failure: can it be a primary immunodeficiency?
AB  - Vaccine failure is a rare condition and the need to investigate a primary
      immunodeficiency is controversial. We present the case of a 4-year-old boy, with
      complete antipneumococcal vaccination, who had necrotising pneumonia with pleural
      effusion and severe pancytopaenia with need for transfusion. A vaccine-serotype
      Streptococcus pneumoniae was isolated in the blood culture. On follow-up,
      detailed medical history, laboratory and genetic investigation led to the
      diagnosis of X linked dyskeratosis congenita. Dyskeratosis congenita is an
      inherited disorder that causes shortening or dysfunction of telomeres, affecting
      mainly rapidly dividing cells (particularly in the skin and haematopoietic
      system). It leads to bone marrow failure, combined immunodeficiency and
      predisposition to cancer. The confirmation of this diagnosis allows genetic
      counselling and medical monitoring of these patients, in order to detect early
      complications such as bone marrow aplasia or malignancies. 

PMID- 24925541
TI  - Warfarin-induced purple toe syndrome successfully treated with apixaban.
AB  - Purple toe syndrome is a recognised adverse effect of warfarin therapy. The
      literature has described resolution of the ischaemic symptoms on withdrawal of
      the warfarin and switching to a low molecular weight heparin alternative. We
      present a case of an 82-year-old man with bilateral blanching vivacious toes and
      a livedo-reticularis type rash developing 2 weeks after being loaded with
      warfarin for first detected atrial fibrillation. Vascular surgical review and
      haematology thrombotic screen did not yield any other pathology and a diagnosis
      of purple toe syndrome due to warfarin was carried out. The warfarin was stopped
      and oral anticoagulation started with an oral factor Xa inhibitor, apixaban with
      resolution of his symptoms. This is the first case report of one of the novel
      oral anticoagulants being used to treat purple toe syndrome.

PMID- 24925542
TI  - Acute oromucosal and palmar desquamation: a severe cutaneous adverse reaction to
      amphotericin and metronidazole.

PMID- 24925543
TI  - Specialized inpatient psychiatry for serious behavioral disturbance in autism and
      intellectual disability.
AB  - Psychiatric hospitalization of children with autism spectrum disorder and/or
      intellectual disability is common, however, the effectiveness of this
      intervention is largely unknown. Thirty-eight clinically-referred children 8-19
      years old admitted to a specialized inpatient psychiatry unit were assessed by a
      consistent caregiver on the Aberrant Behavior Checklist-Irritability (ABC-I)
      subscale at admission, discharge and 2 months post discharge. There was a
      decrease in the mean ABC-I score from admission (27.3, SD 7.4) to discharge
      (11.9, SD 8.8), which was sustained at 2 months post discharge (14.8, SD 9.3) (p
      < 0.001). Seventy-eight percent of the subjects were rated as "Improved" on the
      clinician Clinical Global Impressions Improvement scale at discharge. The study
      is limited by lack of a control group, but offers preliminary evidence for
      specialized inpatient psychiatry as an intervention for serious behavioral
      disturbance in this population. 

PMID- 24925544
TI  - Driving behaviors in adults with autism spectrum disorders.
AB  - This pilot study investigated driving history and driving behaviors between
      adults diagnosed with autism spectrum disorders (ASD) as compared to non-ASD
      adult drivers. Seventy-eight licensed drivers with ASD and 94 non-ASD comparison
      participants completed the Driver Behavior Questionnaire. Drivers with ASD
      endorsed significantly lower ratings of their ability to drive, and higher
      numbers of traffic accidents and citations relative to non-ASD drivers. Drivers
      with ASD also endorsed significantly greater numbers of difficulties on the
      following subscales: intentional violations, F(1, 162) = 6.15, p = .01, eta p (2)
      = .04; mistakes, F(1, 162) = 10.15, p = .002, eta p (2)  = .06; and
      slips/lapses, F(1, 162) = 11.33, p = .001, eta p (2)  = .07. These findings
      suggest that individuals with ASD who are current drivers may experience more
      difficulties in driving behaviors and engage in more problematic driving
      behaviors relative to non-ASD drivers. 

PMID- 24925545
TI  - The effects of similarity, parasocial identification, and source credibility in
      obesity public service announcements on diet and exercise self-efficacy.
AB  - This study examined the effect of the audience's similarity to, and parasocial
      identification with, spokespersons in obesity public service announcements, on
      perceived source credibility, and diet and exercise self-efficacy. The results (N
      = 200) indicated that perceived similarity to the spokesperson was significantly
      associated with three dimensions of source credibility (competence,
      trustworthiness, and goodwill), each of which in turn influenced parasocial
      identification with the spokesperson. Parasocial identification also exerted a
      positive impact on the audiences' diet and exercise self-efficacy. Additionally,
      significant differences were found between overweight viewers and non-overweight
      viewers on perceived similarity, parasocial identification with the spokesperson,
      and source credibility.

PMID- 24925546
TI  - The impact of social support on postpartum depression: The mediator role of self
      efficacy.
AB  - This study aimed to investigate the impact of perceived social support on the
      depression of postpartum women, and mainly focuses on confirming the mediator
      role of self-efficacy. A total of 427 new mothers from two general hospitals in
      Beijing accomplished the Multidimensional Scale of Perceived Social Support,
      General Self-efficacy Scale, and Edinburgh Postnatal Depression Scale. The
      results revealed that both social support and self-efficacy significantly
      correlate with postpartum depression. Structural equation modeling indicated that
      self-efficacy partially mediates the relationship between social support and
      postpartum depression.

PMID- 24925547
TI  - Social support mediates loneliness and depression in elderly people.
AB  - This study investigated the effect of loneliness on depression and further tested
      the mediating effect of social support. A total of 320 elderly persons completed
      the Emotional and Social Loneliness Scale, Multidimensional Scale of Perceived
      Social Support, and Self-Rating Depression Scale. Results revealed that
      loneliness and social support significantly correlated with depression.
      Structural Equation Modeling indicated that social support partially mediates
      loneliness and depression. The final model illustrated a significant path from
      loneliness to depression through social support. This study sheds light on the
      concurrent effects of loneliness and social support on depression, providing
      evidence on how to reduce depression among the elderly.

PMID- 24925548
TI  - Layers of air in the water beneath the floating fern Salvinia are exposed to
      fluctuations in pressure.
AB  - Superhydrophobic, hierarchically structured, technical surfaces (Lotus-effect)
      are of high scientific and economic interest because of their remarkable
      properties. Recently, the immense potential of air-retaining superhydrophobic
      surfaces, for example, for low-friction transport of fluids and drag-reducing
      coatings of ships has begun to be explored. A major problem of superhydrophobic
      surfaces mimicking the Lotus-effect is the limited persistence of the air
      retained, especially under rough conditions of flow. However, there are a variety
      of floating or diving plant and animal species that possess air-retaining
      surfaces optimized for durable water-repellency (Salvinia-effect). Especially
      floating ferns of the genus Salvinia have evolved superhydrophobic surfaces
      capable of maintaining layers of air for months. Apart from maintaining stability
      under water, the layer of air has to withstand the stresses of water pressure (up
      to 2.5 bars). Both of these aspects have an application to create permanent air
      layers on ships' hulls. We investigated the effect of pressure on air layers in a
      pressure cell and exposed the air layer to pressures of up to 6 bars. We
      investigated the suppression of the air layer at increasing pressures as well as
      its restoration during decreases in pressure. Three of the four examined Salvinia
      species are capable of maintaining air layers at pressures relevant to the
      conditions applying to ships' hulls. High volumes of air per surface area are
      advantageous for retaining at least a partial Cassie-Baxter-state under pressure,
      which also helps in restoring the air layer after depressurization. Closed-loop
      structures such as the baskets at the top of the "egg-beater hairs" (see main
      text) also help return the air layer to its original level at the tip of the
      hairs by trapping air bubbles. 

PMID- 24925549
TI  - An unusual presentation of peripheral ossifying fibroma in an elderly man.
AB  - Peripheral ossifying fibroma is a common solitary gingival overgrowth thought to
      arise from the gingival corium, periosteum or periodontal ligament. Ossifying
      fibroma has the propensity to occur in cranial bones, but the peripheral variety
      shows a close relationship with the periodontal ligament and adjacent alveolar
      bone. It is more commonly seen in women (predilection of 3:1) and usually at a
      young age. This report describes an unusual presentation in an elderly man and
      presents a systematic way of diagnosing and treating peripheral ossifying
      fibroma. 

PMID- 24925550
TI  - Prehospital use of ketamine for analgesia and procedural sedation by critical
      care paramedics in the UK: a note of caution?

PMID- 24925551
TI  - Development of a novel low-temperature deposition machine using screw extrusion
      to fabricate poly(l-lactide-co-glycolide) acid scaffolds.
AB  - Scaffolds are of great importance to the success of tissue engineering. Poly(l
      lactide-co-glycolide) acid is one of the most commonly used biopolymers. This
      study develops a novel low-temperature deposition machine using screw extrusion
      to fabricate poly(l-lactide-co-glycolide) acid scaffolds. The screw extrusion
      process of poly(l-lactide-co-glycolide) acid is analysed, and the relationship
      between flow rate and processing parameters is examined. This relationship
      provides guidelines for optimizing the processing parameters. The major
      components and design strategy of the fabrication system are introduced. Measures
      are proposed to control the leakage of materials, and optimal processing
      parameters are determined. The machine is also equipped with a double-screw
      extrusion nozzle system; preliminary results demonstrate its capacity to
      fabricate gradient scaffolds. Porous structure characterization using mercury
      porosimetry demonstrates that the fabrication system is able to fabricate poly(l
      lactide-co-glycolide) acid scaffolds that are both macroporous and microporous.

PMID- 24925552
TI  - Siberia.

PMID- 24925553
TI  - Effect of repeated application of low-intensity pulsed electromagnetic fields
      (PEMF) on gait speed in older adults with a history of falls.

PMID- 24925554
TI  - Association between hearing impairment and frailty in older adults.

PMID- 24925555
TI  - Association between hearing loss and healthcare expenditures in older adults.

PMID- 24925556
TI  - Determinants of perceived emotional recovery and perceived change in health after
      a disaster.

PMID- 24925557
TI  - Preferences of older adults with cancer for involvement in decision-making about
      research participation.

PMID- 24925558
TI  - Detection of hypovitaminosis D in older adults: a classification tree analysis.

PMID- 24925559
TI  - Noninvasive ventilation in older adults admitted to a pneumogeriatric unit.

PMID- 24925560
TI  - Outbreak of Streptococcus pneumoniae serotype 3 pneumonia in extremely elderly
      people in a nursing home unit in Kanagawa, Japan, 2013.

PMID- 24925561
TI  - Severe euvolemic hyponatremia with urinary retention: a case report.

PMID- 24925562
TI  - Cannabis for intractable nausea after bilateral cerebellar stroke.

PMID- 24925563
TI  - A disease affecting all ages: Crohn's disease.

PMID- 24925564
TI  - Scabies manifesting as bullous pemphigus in a nursing home resident.

PMID- 24925565
TI  - A rare case of vagal syncope.

PMID- 24925566
TI  - Hodgkin's lymphoma in a 96-year-old woman: a diagnostic, therapeutic, and
      prognostic dilemma.

PMID- 24925567
TI  - Risk of proton pump inhibitor-induced mild hyponatremia in older adults.

PMID- 24925568
TI  - Analysis of gait speed and vitamin D deficiency.

PMID- 24925569
TI  - Response to Bahat.

PMID- 24925570
TI  - Response to Safer et al.

PMID- 24925571
TI  - Comment on "Sarcopenic obesity and risk of cardiovascular disease and mortality:
      a population-based cohort study of older men".

PMID- 24925572
TI  - Nutritional status and pressure ulcers. Risk assessment and estimation in older
      adults.

PMID- 24925573
TI  - Response to Malafarina and colleagues.

PMID- 24925574
TI  - Subtilase from Beauveria sp.: conformational and functional investigation of
      unusual stability.
AB  - Retention of total activity of the subtilisin-like serine protease from Beauveria
      sp. MTCC 5184 (Bprot) in the vicinity of (1) 3 M GdnHCl for 12 h, (2) 50%
      methanol and dimethyl sulfoxide each for 24 h, and (3) proteolytic enzymes
      (trypsin, chymotrypsin, and proteinase K) for 48 h led to expect the enzyme to be
      a kinetically stable protein. Also, the structure of the protein was stable at pH
      2.0. Biophysical characterization and conformational transitions were monitored
      using steady-state and time-resolved fluorescence, FTIR, and CD spectroscopy.
      Single tryptophan in the protein exists as two conformers, in hydrophobic and
      polar environment. The secondary structure of Bprot was stable in 3 M GdnHCl as
      seen in far-UV CD spectra. The active fraction of Bprot obtained from size
      exclusion chromatography in the presence of GdnHCl (1.0-3.0 M) eluted at reduced
      retention time. The peak area of inactive or denatured protein with the same
      retention time as that of native protein increased with increasing concentration
      of denaturant (1.0-4.0 M GdnHCl). However, the kinetics of GdnHCl-induced
      unfolding as studied from intrinsic fluorescence revealed k unf of native protein
      to be 5.407 * 10(-5) s(-1) and a half-life of 3.56 h. The enzyme is
      thermodynamically stable in spite of being resistant to the denaturant, which
      could be due to the effect of GdnHCl imparting rigidity to the active fraction
      and simultaneously unfolding the partially unfolded protein that exists in
      equilibrium with the folded active protein. Thermal and pH denaturation of Bprot
      exhibited interesting structural transitions.

PMID- 24925576
TI  - Quality and the curate's egg.

PMID- 24925575
TI  - A conserved cationic motif enhances membrane binding and insertion of the
      chloride intracellular channel protein 1 transmembrane domain.
AB  - The chloride intracellular channel protein 1 (CLIC1) is unique among eukaryotic
      ion channels in that it can exist as either a soluble monomer or an integral
      membrane channel. CLIC1 contains no known membrane-targeting signal sequences and
      the environmental factors which promote membrane binding of the transmembrane
      domain (TMD) are poorly understood. Here we report a positively charged motif at
      the C-terminus of the TMD and show that it enhances membrane partitioning and
      insertion. A 30-mer TMD peptide was synthesized in which the positively charged
      motif was replaced by three glutamate residues. The peptide was examined in 2,2,2
      trifluoroethanol (TFE), sodium dodecyl sulfate micelles and 1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphocholine liposomes using size-exclusion chromatography, far-UV
      CD, and fluorescence spectroscopy. The motif appears to enhance membrane
      interaction via electrostatic contacts and functions as an electrostatic plug to
      anchor the TMD in membranes. In addition, the motif is also involved in
      orientating the TMD with respect to the cis and trans faces of the membrane.
      These findings shed light on the intrinsic and environmental factors that promote
      the spontaneous conversion of CLIC1 from a water-soluble to a membrane-bound
      protein. 

PMID- 24925578
TI  - Palliative care development in Latin America: an analysis using macro indicators.
AB  - BACKGROUND: Recently, the Latin American Association for Palliative Care
      developed 10 indicators to monitor the development of palliative care and enhance
      the development of regional and national strategies. AIM: To compare the status
      of palliative care development across Latin American nations using the Latin
      American Association for Palliative Care indicators and to classify the countries
      into three levels of palliative care development. METHODS: A secondary analysis
      using the following indicators (number of indicators in each category): Policy
      (1), Education (3), Service Provision (3), and Opioids (3). A Latin American
      Association for Palliative Care Index was constructed adding the standard score
      (z-score) of each indicator. SETTING/PARTICIPANTS: Nineteen Spanish and
      Portuguese-speaking countries of Latin America. RESULTS: Indicators significantly
      associated with the number of palliative care services per million inhabitants
      included: the proportion of medical schools with palliative care at the
      undergraduate level (p = 0.003), the number of accredited physicians working in
      palliative care (p = 0.001), and opioids consumed per capita (p = 0.032).
      According to the Latin American Association for Palliative Care Index, Costa Rica
      registered the highest score (8.1). Three ranking groups were built to measure
      palliative care development; Costa Rica, Chile, Mexico, and Argentina ranked in
      the high group, while Bolivia, Honduras, Dominican Republic, and Guatemala ranked
      in the lowest group. CONCLUSION: Most of the Latin American Association for
      Palliative Care indicators are useful for assessing national levels of palliative
      care development. These indicators may be applicable to other world regions.
      Additional studies are needed to evaluate the specificity of each indicator.

PMID- 24925579
TI  - Instabilities in the ferro- and antiferroelectric lead perovskites driven by
      transition metal ion mass: from PbTiO3 via PbZrO3 to PbHfO3.
AB  - The lattice dynamics of Pb-containing perovskite oxides are investigated
      theoretically for the transition metal series Ti, Zr, Hf, in order to elucidate
      their commonalities and their distinctions. For all three compounds, pronounced
      precursor effects are found to their phase transition temperatures, which get
      more pronounced the heavier the central transition metal ion is. In addition, a
      competition between a polar and an antiferrodistortive instability is predicted
      to take place, which is strongly mass dependent. While in PbTiO3 the polar
      instability wins, both instabilities are active in PbZrO3, whereas in PbHfO3 the
      antiferrodistortive phase transition dominates the dynamics. For all three
      compounds, marked anomalies in the elastic constants are predicted, which are
      most pronounced in PbHfO3. Experimental results for elastic anomalies preceding
      the phase transition, which agree qualitatively with the model calculations are
      presented for PbHfO3. 

PMID- 24925580
TI  - Analysis of joint force and torque for the human and non-human ape foot during
      bipedal walking with implications for the evolution of the foot.
AB  - The feet of apes have a different morphology from those of humans. Until now, it
      has merely been assumed that the morphology seen in humans must be adaptive for
      habitual bipedal walking, as the habitual use of bipedal walking is generally
      regarded as one of the most clear-cut differences between humans and apes. This
      study asks simply whether human skeletal proportions do actually enhance foot
      performance during human-like bipedalism, by examining the influence of foot
      proportions on force, torque and work in the foot joints during simulated bipedal
      walking. Skeletons of the common chimpanzee, orangutan, gorilla and human were
      represented by multi-rigid-body models, where the components of the foot make
      external contact via finite element surfaces. The models were driven by identical
      joint motion functions collected from experiments on human walking. Simulated
      contact forces between the ground and the foot were found to be reasonably
      comparable with measurements made during human walking using pressure- and force
      platforms. Joint force, torque and work in the foot were then predicted. Within
      the limitations of our model, the results show that during simulated human-like
      bipedal walking, (1) the human and non-human ape (NHA) feet carry similar joint
      forces, although the distributions of the forces differ; (2) the NHA foot incurs
      larger joint torques than does the human foot, although the human foot has higher
      values in the first tarso-metatarsal and metatarso-phalangeal joints, whereas the
      NHA foot incurs higher values in the lateral digits; and (3) total work in the
      metatarso-phalangeal joints is lower in the human foot than in the NHA foot. The
      results indicate that human foot proportions are indeed well suited to
      performance in normal human walking. 

PMID- 24925581
TI  - DJ-1 contributes to adipogenesis and obesity-induced inflammation.
AB  - Adipose tissue functions as an endocrine organ, and the development of systemic
      inflammation in adipose tissue is closely associated with metabolic diseases,
      such as obesity and insulin resistance. Accordingly, the fine regulation of the
      inflammatory response caused by obesity has therapeutic potential for the
      treatment of metabolic syndrome. In this study, we analyzed the role of DJ-1
      (PARK7) in adipogenesis and inflammation related to obesity in vitro and in vivo.
      Many intracellular functions of DJ-1, including oxidative stress regulation, are
      known. However, the possibility of DJ-1 involvement in metabolic disease is
      largely unknown. Our results suggest that DJ-1 deficiency results in reduced
      adipogenesis and the down-regulation of pro-inflammatory cytokines in vitro.
      Furthermore, DJ-1-deficient mice show a low-level inflammatory response in the
      high-fat diet-induced obesity model. These results indicate previously unknown
      functions of DJ-1 in metabolism and therefore suggest that precise regulation of
      DJ-1 in adipose tissue might have a therapeutic advantage for metabolic disease
      treatment. 

PMID- 24925582
TI  - Henoch-Schonlein purpura in 535 Chinese children: clinical features and risk
      factors for renal involvement.
AB  - OBJECTIVES: To analyse the clinical features of Henoch-Schonlein purpura (HSP)
      with or without nephritis in Chinese children and to determine the risk factors
      for renal involvement. METHODS: Patient characteristics, clinical parameters and
      laboratory data were retrospectively analysed in patients with HSP with or
      without nephritis. Logistic regression analysis was used to identify the risk
      factors for renal involvement. RESULTS: A total of 535 patients with HSP were
      included in the study. HSP nephritis occurred in 267 patients (49.9%), ranging
      from isolated haematuria in 5.2%, mild proteinuria in 77.5%, moderate proteinuria
      in 6.4% and severe proteinuria in 10.9% of cases. In 90% of the cases, nephritis
      developed within 1 week of HSP onset; 98.5% of the cases with nephritis developed
      the condition within 1 month. Risk factors for the development of nephritis were
      age >=6 years, purpura on sites other than the lower limbs and the presence of
      occult blood in the stool. CONCLUSION: These results suggest that patients aged
      >=6 years, or who have purpura on the upper limbs or face, or who have occult
      blood in the stool should be particularly monitored for signs of nephritis.

PMID- 24925583
TI  - Relationship between toll-like receptor 4 levels in aorta and severity of
      atherosclerosis.
AB  - OBJECTIVE: To investigate the relationship between levels of toll-like receptor 4
      (TLR4) protein in aortic tissue and the severity of atherosclerosis in patients
      undergoing coronary artery bypass graft (CABG) surgery. METHODS: Samples of
      ascending aorta and renal artery were collected from patients undergoing CABG
      surgery or kidney donation, respectively. TLR4 levels were determined by
      immunohistochemistry. Coronary angiography was performed to determine
      atherosclerosis severity via Gensini score. RESULTS: TLR4 was present at high
      levels in aortic tissues from patients (n = 46), and was absent from renal artery
      tissue (controls; n = 11). There was a significant positive correlation between
      Gensini score and TLR4 level in the patient group. CONCLUSIONS: TLR4 may play an
      important role in atherosclerosis and could be a potential therapeutic target for
      treatment of coronary artery disease. Discarded aortic tissue obtained during
      CABG surgery provides a new approach to the study of the pathogenesis of
      atherosclerosis.

PMID- 24925584
TI  - Clinical effectiveness of Novolin(r) 30R versus Lantus(r) combined with
      Glucobay(r) treatment in elderly patients with type 2 diabetes mellitus
      controlled by oral hypoglycaemic agents: A randomized study.
AB  - OBJECTIVE: To compare the treatment effects of Novolin(r) 30R(a), versus
      Lantus((r)a) combined with acarbose (Glucobay(r)), in elderly patients with type
      2 diabetes mellitus. METHODS: Patients (aged > 60 years) with type 2 diabetes
      mellitus were randomized to receive either Novolin(r) 30R(a) (initial dose 0.5
      IU/kg) or Lantus((r)a) (initial dose 0.2 IU/kg) combined with 50 mg acarbose.
      After a 32-week treatment period, the following parameters were measured: blood
      glucose control; blood lipid levels; body mass index; proportion of patients
      achieving a glycosylated haemoglobin (HbA1c) level <7.5%; rate of hypoglycaemic
      events; change in fasting blood glucose levels from baseline in patients
      stratified according to their baseline HbA1c level. RESULTS: A total of 188
      patients were enrolled in the study. After 32 weeks' treatment, compared with
      baseline levels, there were significant reductions in FBG, 2 h-postprandial blood
      glucose during an oral glucose tolerance test, HbA1c, total cholesterol,
      triglycerides and low-density lipoprotein cholesterol values in both groups.
      Although there were fewer hypoglycaemic events in the Lantus(r) combined with
      Glucobay(r) group compared with the Novolin(r) 30R group, the difference was not
      significant. CONCLUSION: Novolin(r) 30R and Lantus(r) combined with acarbose both
      had beneficial effects on blood glucose control and blood lipid levels in elderly
      patients with type 2 diabetes mellitus.

PMID- 24925585
TI  - Reliability of the senior fitness test in community-dwelling older people with
      cognitive impairment.
AB  - BACKGROUND AND PURPOSE: In older people with cognitive impairment, we require
      reliable and valid measures to assess physical fitness and to measure change, for
      example, as a result of an exercise intervention. The purpose of our study was to
      determine the relative and absolute test-retest reliability of the Senior Fitness
      Test (SFT) in older people with cognitive impairment. METHODS: A test-retest
      reliability study was conducted for the Senior Fitness Test in older people with
      cognitive impairment. Participants were tested at two time points with a time
      interval of 24 hours to 1 week between tests. The Intraclass Correlation
      Coefficient model 3.1 (ICC, 3.1) with 95% confidence intervals (CIs) was used as
      a measure of relative reliability. The standard error of measurement and minimal
      detectable change (MDC) were used to measure absolute reliability. RESULTS: The
      ICC reflected very high reliability (0.93-0.98) in all SFT items, indicating that
      there was no systematic error in the measurements. MDC values at the 90% CIs were
      calculated: chair stand test = 2.0 repetitions, armcurl test = 2.3 repetitions,
      chair sit and reach test = 6.0 cm, back scratch test = 4.6 cm, 2.45-m up-and-go
      test = 1.4 seconds and 6-minute walk test = 37.1 metres. DISCUSSION: The SFT
      battery showed high to very high test-retest reliability and thus may be suitable
      for detecting changes in physical fitness and evaluating physical fitness in
      older people with cognitive impairment, both in research and for clinical
      purposes.

PMID- 24925586
TI  - Treatment of severe and/or refractory ANCA-associated vasculitis.
AB  - Most patients presenting with systemic necrotizing vasculitides improve when they
      are adequately treated. The presence of life-threatening manifestations or
      visceral involvement modifying organ function characterizes severe vasculitis,
      confirmed by disease-severity scores. Sequelae cannot always be predicted and
      prevented but organ involvement present at disease onset requires rapid
      therapeutic intervention. Some patients present a persistent active disease,
      which does not respond to treatments and deserve other drugs or combination of
      drugs. The therapeutic options for severe and/or relapsing and refractory
      diseases are described. 

PMID- 24925587
TI  - Vaccinations for rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious
      disease-related morbidity and mortality and have twice the risk of acquiring a
      severe infection compared to the general population. This increased risk is not
      only a result of the autoimmune disease but is also attributed to the
      immunosuppressive therapies that are commonly used in this patient population.
      Given the increase in infection-related risks in RA, there is great interest in
      mitigating such risk. A number of vaccines are available to the rheumatologist,
      with a handful that are of importance for RA patients in the United States. The
      goal of this paper is to highlight the most recent literature on the key vaccines
      and the specific considerations for the rheumatologist and their RA patients,
      with a particular focus on influenza, pneumococcal, and herpes zoster vaccines.
      It is important for rheumatologist to understand and be aware of which vaccines
      are live and what potential contraindications exist for giving vaccines to RA
      patients. 

PMID- 24925588
TI  - Vaccination in paediatric rheumatology.
AB  - As awareness of the risk of vaccine-preventable diseases for children with
      rheumatic diseases has increased, vaccination has become an important clinical
      consideration and focus of research in paediatric rheumatology. Conflicting
      reports in the literature and differing advice from national bodies regarding the
      safety of different vaccines for this patient population have led to confusion in
      the minds of many rheumatologists as to what is appropriate. This article will
      provide an overview of crucial aspects of the recently published European League
      Against Rheumatism recommendations regarding vaccination of paediatric patients
      with rheumatic disease, and will review advances in this field since their
      publication. 

PMID- 24925590
TI  - Speech and language therapists' approaches to communication intervention with
      children and adults with profound and multiple learning disability.
AB  - BACKGROUND: People with profound intellectual and multiple disabilities (PMLD)
      have communication impairments as one defining characteristic. AIMS: To explore
      speech and language therapists' (SLTs) decision making in communication
      interventions for people with PMLD, in terms of the intervention approaches used,
      the factors informing the decisions to use specific interventions and the extent
      to which the rationales underpinning these decisions related to the components of
      evidence based practice (EBP), namely empirical evidence, clinical experience and
      client/carer views and values. METHODS & PROCEDURES: A questionnaire on
      communication assessment and intervention for people with PMLD was sent to SLTs
      in the UK to elicit information on: the communication intervention approaches
      they used; their rationales for their intervention choices; their use of
      published evidence to inform decision making. OUTCOMES & RESULTS: Intensive
      interaction and objects of reference were the communication interventions most
      often used with people with PMLD, with some differences between children and
      adults evident. Rationales provided conformed somewhat to the EBP framework
      though extension of the existing framework and addition of practical and
      organizational considerations led to a revised typology of rationale for decision
      making. Rationales most frequently related to the empowerment, development and
      behavioural preferences of the person with PMLD. CONCLUSIONS & IMPLICATIONS:
      Empirical research evidence was seldom mentioned by SLTs as informing
      intervention decision making leading to very diverse practice. There is a need
      for further research on the effectiveness of commonly used but under-evaluated
      interventions. There is also a need to alert SLTs to the evidence base supporting
      other approaches, particularly switch-based, cause and effect approaches.

PMID- 24925589
TI  - Pulmonary, renal and neurological comorbidities in patients with ankylosing
      spondylitis; implications for clinical practice.
AB  - Ankylosing spondylitis (AS) is associated with several comorbidities which
      contribute significantly to morbidity and mortality and add to the complexity of
      management. In addition to the well known extra-articular manifestations and
      increased cardiovascular risk, several pulmonary, renal, and neurological
      complications which have been associated with AS deserve equal attention. Whereas
      a clear link has been established for some manifestations, the evidence for other
      associations is less clear. Interstitial lung disease, apical fibrosis, secondary
      infection, and ventilatory restriction from reduced chest wall movement are well
      known pulmonary complications; more recently an association with sleep apnoea has
      been suggested. Renal amyloidosis and IgA nephropathy remain a treatment
      challenge which may respond to anti-TNF therapy. Atlanto axial subluxation and
      vertebral fractures can result in serious neurological complications and are
      notoriously difficult to diagnose unless a high level of suspicion is maintained.
      Despite several reports linking AS with demyelination a true link remains to be
      proved. This review discusses the prevalence, pathophysiology, and management of
      pulmonary, renal, and neurological complications, and implications for clinical
      practice. 

PMID- 24925591
TI  - Seasonal characteristics of oxalic acid and related SOA in the free troposphere
      of Mt. Hua, central China: implications for sources and formation mechanisms.
AB  - PM10 aerosols from the summit of Mt. Hua (2060 m a.s.l) in central China during
      the winter and summer of 2009 were analyzed for dicarboxylic acids,
      ketocarboxylic acids and alpha-dicarbonyls. Molecular composition of dicarboxylic
      acids (C2-C11) in the free tropospheric aerosols reveals that oxalic acid (C2,
      399 +/- 261 ng m(-3) in winter and 522 +/- 261 ng m(-3) in summer) is the most
      abundant species in both seasons, followed by malonic (C3) and succinic (C4)
      acids, being consistent with that on ground levels. Most of the diacids are more
      abundant in summer than in winter, but adipic (C6) and phthalic (Ph) acids are
      twice lower in summer, suggesting more significant impact of anthropogenic
      pollution on the wintertime alpine atmosphere. Moreover, glyoxal (Gly) and
      methylglyoxal (mGly) are also lower in summer (12 +/- 6.1 ng m(-3)) than in
      winter (22 +/- 13 ng m(-3)). As both dicarbonyls are a major precursor of C2,
      their seasonal variation patterns, which are opposite to those of the diacids,
      indicate that the mountain troposphere is more oxidative in summer. C2 showed
      strong linear correlations with levoglucosan in winter and oxidation products of
      isoprene and monoterpene in summer. PCA analysis further suggested that the
      wintertime C2 and related SOA in the Mt. Hua troposphere mostly originate from
      photochemical oxidations of anthropogenic pollutants emitted from biofuel and
      coal combustion in lowland regions. On contrast, the summertime C2 and related
      SOA mostly originate from further oxidation of the mountainous isoprene and
      monoterpene oxidation products. The AIM model calculation results showed that
      oxalic acid concentration well correlated with particle acidity (R(2)=0.60) but
      not correlated with particle liquid water content, indicating that particle
      acidity favors the organic acid formation because aqueous-phase C2 production is
      the primary mechanism of C2 formation in ambient aerosols and is driven by acid
      catalyzed oxidation.

PMID- 24925592
TI  - Influence of gestational diabetes mellitus on neonatal weight outcome in twin
      pregnancies.
AB  - AIMS: To evaluate the influence of gestational diabetes mellitus on neonatal
      birthweight, macrosomia and weight discrepancy in twin neonates. METHODS: An
      observational retrospective study was performed. One hundred and six women with
      gestational diabetes and twin pregnancy and 166 twin controls who delivered
      viable fetuses > 24 weeks were included. Impact of maternal pre-pregnancy BMI,
      smoking habit, method of conception, chorionicity, gestational age at delivery,
      mode of delivery and hypertensive complications were also analysed. The effect of
      maternal hyperglycaemia and metabolic control in gestational diabetes pregnancies
      was assessed. RESULTS: Gestational hypertension and pre-eclampsia were
      significantly higher in the group with gestational diabetes (21.5% vs. 6.3%, P =
      0.007 and 6.2% vs. 0%, P = 0.025). There were no differences in the incidence of
      macrosomia (5.7% vs. 7.2%, P = 0.803), large for gestational age (10.3% vs.
      13.2%, P = 0.570), small for gestational age (10.3% vs. 12.0%, P = 0.701),
      severely small for gestational age (6.6% vs. 7.8%, P = 0.814) or weight
      discrepancy (20.6% vs. 15.2%, P = 0.320) in the group with gestational diabetes
      compared with twin pregnancies without diabetes. There were no differences when
      comparing insulin-requiring gestational diabetes pregnancies and twins without
      diabetes for any of the neonatal weight outcomes. There was no relationship
      between third trimester HbA1c and neonatal birthweight or infant birthweight
      ratio. CONCLUSION: Gestational diabetes did not increase the risk of macrosomia
      or weight discrepancy of twin newborns. Furthermore, glycaemic control did not
      influence the rate of any of the weight outcomes in our study population. In twin
      pregnancies, gestational diabetes was associated with a higher risk of
      gestational hypertension and pre-eclampsia.

PMID- 24925594
TI  - Protein intake, chronic liver diseases, and hepatocellular carcinoma.

PMID- 24925593
TI  - MRI-guided high-intensity focused ultrasound ablation of bone: evaluation of
      acute findings with MR and CT imaging in a swine model.
AB  - PURPOSE: To evaluate hyperacute (<1 hour) changes on magnetic resonance (MR) and
      computed tomography (CT) imaging following MR-guided high-intensity focused
      ultrasound (MRgHIFU) in a swine bone model as a function of sonication number and
      energy. MATERIALS AND METHODS: Experimental procedures received approval from the
      local Institutional Animal Care and Use Committee. MRgHIFU was used to create
      distal and proximal ablations in the right femur of eight pigs. Each target was
      dosed with four or six sonications within similar volumes. The energy dosed to
      the distal target was higher (419 +/- 19 J) than the proximal target (324 +/- 17
      J). The targeted femur and contralateral control were imaged before and after
      ablation using MR at 3T. Qualitative changes in signal on T1-weighted, T2
      weighted, and T1-weighted postcontrast images were assessed. Ablation dimensions
      were calculated from postcontrast MRI. The 64-slice CT images were also obtained
      before and after ablation and qualitative changes were assessed. RESULTS: MRgHIFU
      bone ablation size measured on average 8.5 * 21.1 * 16.2 mm (transverse *
      craniocaudal * anteroposterior). Interestingly, within similar prescribed
      volumes, increasing the number of sonications from 4 to 6 increased the depth of
      the intramedullary hypoenhanced zone from 2.9 mm to 6.5 mm (P < 0.001). There was
      no difference in the appearance of low versus high energy ablations. CT imaging
      did not show structural abnormalities. CONCLUSION: The number of MRgHIFU focal
      sonications can be used to increase the depth of treatment within the targeted
      bone. Unlike CT, T2-weighted and contrast-enhanced MR demonstrated the hyperacute
      structural changes in the femur and surrounding soft tissue.

PMID- 24925595
TI  - Postoperative serum methylation levels of TAC1 and SEPT9 are independent
      predictors of recurrence and survival of patients with colorectal cancer.
AB  - BACKGROUND: Serum carcinoembryonic antigen (CEA) is the only marker recommended
      for surveillance of colorectal cancer (CRC) recurrence; its sensitivity and
      specificity, however, are suboptimal. This study sought to evaluate the values of
      postoperative serum methylation levels of 7 genes for prognostication and
      especially for recurrence detection after curative resection. METHODS: This
      prospective cohort study included 150 patients with stage I-III CRC from whom 3
      consecutive blood sampling was taken 1 week before, and 6 months and 1 year after
      operation. Methylation levels of 7 genes were evaluated via quantitative
      methylation-specific polymerase chain reaction. Serum CEA was measured in
      parallel. Univariate and multivariate survival analyses were followed by
      construction of receiver operating characteristic curves for recurrence
      detection. RESULTS: After a median follow-up of 59 months, 43 patients (28.7%)
      developed recurrent lesions. High serum methylation levels of TAC1 in serum at 6
      month follow-up (6M-FU), and SEPT9 at 1-year follow-up (1Y-FU) were independent
      predictors for tumor recurrence and unfavorable cancer-specific survival (CSS) (P
      < .05 in all tests). Serum NELL1 methylation levels were significant alone for
      CSS at both 6M-FU and 1Y-FU, but not for disease-free survival. Dynamic changes
      of TAC1 and SEPT9 with methylation increment were also independently predictive
      for recurrence (P < .05 in all tests). More importantly, TAC1 at 6M-FU and SEPT9
      at 1Y-FU exhibited earlier detection of potential recurrences compared with
      concurrent serum CEA. CONCLUSIONS: Levels of TAC1 and SEPT9 methylation detected
      in postoperative sera of patients with CRC appear to be novel promising
      prognostic markers and may probably be considered for monitoring of CRC
      recurrence.

PMID- 24925596
TI  - Arthrobacter bambusae sp. nov., isolated from soil of a bamboo grove.
AB  - A Gram-stain-positive, aerobic, motile by gliding, rod-shaped bacterial strain,
      THG-GM18(T), was isolated from soil of a bamboo grove. Strain THG-GM18(T) was
      able to grow in the presence of up to 6.0 % (w/v) NaCl, at 4-37  degrees C and at
      pH 7.0-10.0 in R2A medium. Based on 16S rRNA gene sequence similarity, strain THG
      GM18(T) was closely related to species of the genus Arthrobacter. The most
      closely related strains to strain THG-GM18(T) are Arthrobacter ramosus CCM
      1646(T) (98.5 % similarity), Arthrobacter nitroguajacolicus G2-1(T) (98.4 %),
      Arthrobacter nicotinovorans DSM 420(T) (98.2 %), Arthrobacter aurescens DSM
      20116(T) (98.1 %) and Arthrobacter chlorophenolicus A6(T) (98.0 %). Strain THG
      GM18(T) possessed chemotaxonomic properties consistent with those of members of
      the genus Arthrobacter, such as peptidoglycan type A3alpha (l-Lys-l-Ala-l-Thr-l
      Ala), MK-9 as major menaquinone and anteiso- and iso-branched compounds (anteiso
      C15 : 0, iso-C16 : 0 and anteiso-C17 : 0) as major cellular fatty acids. The
      polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, an
      unidentified phosphoglycolipid, unidentified phospholipids, unidentified
      aminolipids, an unidentified glycolipid and unidentified lipids. The G+C content
      of the genomic DNA was 61.0 mol%. The DNA-DNA relatedness values between strain
      THG-GM18(T) and its closest phylogenetic neighbours were below 26.0 %. The
      results of physiological and biochemical tests allowed the differentiation of
      strain THG-GM18(T) from species of the genus Arthrobacter with validly published
      names. Arthrobacter bambusae sp. nov. is the proposed name, and the type strain
      is THG-GM18(T) ( = KACC 17531(T) = JCM 19335(T)). 

PMID- 24925597
TI  - Barnettozyma siamensis f.a., sp. nov., a lipid-accumulating ascomycete yeast
      species.
AB  - Two strains, DMKU-UbN24(1)(T) and DMKU-CPN24(1), of a novel yeast species were
      obtained from soil and palm oil fruit, respectively, collected in Thailand by an
      enrichment isolation technique using a nitrogen-limited medium containing
      glycerol as the sole source of carbon. On the basis of morphological,
      biochemical, physiological and chemotaxonomic characteristics and sequence
      analysis of the D1/D2 region of the large subunit (LSU) rRNA gene and the
      internal transcribed spacer (ITS) region, the two strains were found to represent
      a novel species of the genus Barnettozyma although the formation of ascospores
      was not observed. The novel species was related most closely to the type strain
      of Candida montana but differed by 5.4 % nucleotide substitutions in the D1/D2
      region of the LSU rRNA gene and by 10.3-10.5 % nucleotide substitutions in the
      ITS region. The name Barnettozyma siamensis f.a., sp. nov. is proposed. The type
      strain is DMKU-UbN24(1)(T) ( = BCC 61189(T) = NBRC 109701(T) = CBS 13392(T)). 

PMID- 24925598
TI  - Papiliotrema siamense f.a., sp. nov., a yeast species isolated from plant leaves.
AB  - Two strains representing a novel species were isolated from the external surface
      of a sugar cane leaf (DMKU-SP85(T)) and tissue of a rice leaf (DMKU-RE97)
      collected in Thailand. On the basis of morphological, biochemical, physiological
      and chemotaxonomic characteristics, and sequence analysis of the D1/D2 region of
      the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS)
      region, the two strains were determined to represent a novel species of the genus
      Papiliotrema although sexual reproduction was not observed. The sequences of the
      D1/D2 region of the LSU rRNA gene and ITS region of the two strains were
      identical, but differed from those of the type strain of Cryptococcus nemorosus
      by 0.6 % nucleotide substitutions (four nucleotide substitutions out of 597
      nucleotides) in the D1/D2 region of the LSU rRNA gene and 1.8 % nucleotide
      substitutions (nine nucleotide substitutions out of 499 nucleotides) in the ITS
      region. The name Papiliotrema siamense f.a., sp. nov. is proposed. The type
      strain is DMKU-SP85(T)( = BCC 69499(T) = CBS 13330(T)). 

PMID- 24925599
TI  - Parafilimonas terrae gen. nov., sp. nov., isolated from greenhouse soil.
AB  - A Gram-stain-negative, short rod-shaped, non-flagellated, yellow bacterium,
      designated strain 5GHs7-2(T), was isolated from a greenhouse soil sample in South
      Korea. 16S rRNA gene sequence analysis of strain 5GHs7-2(T) indicated that the
      isolate belonged to the family Chitinophagaceae, and exhibited the highest
      sequence similarities with members of the genera Terrimonas (89.2-92.6 %),
      Sediminibacterium (90.8-91.4 %) and Chitinophaga (89.2-91.7 %), Filimonas lacunae
      YT21(T) (91.7 %), members of the genus Segetibacter (90.2-91.6 %),
      Parasegetibacter luojiensis RHYL-37(T) (90.9 %) and Flavihumibacter petaseus
      T41(T) (91.2 %). Flexirubin-type pigments were present. The major cellular fatty
      acids of the novel strain were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G.
      The polar lipid profile consisted of a large amount of phosphatidylethanolamine,
      and moderate and small amounts of several unknown aminolipids and lipids. The
      only respiratory quinone of strain 5GHs7-2(T) was MK-7, and the DNA G+C content
      was 47.6 mol%. On the basis of the evidence presented, it is concluded that
      strain 5GHs7-2(T) represents a novel species of a new genus in the family
      Chitinophagaceae, for which the name Parafilimonas terrae gen. nov., sp. nov. is
      proposed. The type strain of the type species is 5GHs7-2(T) ( = KACC 17343(T) =
      DSM 28286(T)). 

PMID- 24925600
TI  - Flip-angle mapping of 31P coils by steady-state MR spectroscopic imaging.
AB  - PURPOSE: Phosphorus ((31)P) MR spectroscopic imaging (MRSI) is primarily applied
      with sensitive, surface radiofrequency (RF) coils that provide inhomogeneous
      excitation RF field (B1(+)) and rough localization due to their B1(+) and
      sensitivity (B1(-)) profiles. A careful and time-consuming pulse adjustment and
      an accurate knowledge of flip angle (FA) are mandatory for quantification
      corrections. MATERIALS AND METHODS: In this study, a simple, fast, and universal
      (31)P B1(+) mapping method is proposed, which requires fast steady-state MRSI
      (typically one sixth of normal measurement time) in addition to the typical MRSI
      acquired within the examination protocol. The FA maps are calculated from the
      ratio of the signal intensities acquired by these two measurements and were used
      to correct for the influence of B1(+) on the metabolite maps. RESULTS: In vitro
      tests were performed on two scanners (3 and 7 Tesla) using a surface and a volume
      coil. The calculated FA maps were in good agreement with adjusted nominal FAs and
      the theoretical calculation using the Biot-Savart law. The method was
      successfully tested in vivo in the calf muscle and the brain of healthy
      volunteers (n = 4). The corrected metabolite maps show higher homogeneity
      compared with their noncorrected versions. CONCLUSION: The calculated FA maps
      helped with B1(+) inhomogeneity corrections of acquired in vivo data, and should
      also be useful with optimization and testing of pulse performances, or with the
      construction quality tests of new dual-channel (1)H/(31)P coils.

PMID- 24925601
TI  - Loop-mediated isothermal amplification of vanA gene enables a rapid and naked-eye
      detection of vancomycin-resistant enterococci infection.
AB  - Vancomycin-resistant enterococci (VRE) are one of the leading causes of
      nosocomial infection at intensive care unit (ICU). A rapid and sensitive
      detection of VRE infection is in high demand for timely and suitable antibiotic
      treatment. Here, we optimized a distinct DNA-based diagnostic technique, loop
      mediated isothermal amplification (LAMP) for a rapid detection of the presence of
      vanA gene, a critical component of the gene cluster required for vancomycin
      resistance. Amplification efficiency was optimal at 62 degrees C and with 2mM
      MgSO4. The detection limit of the DNA template was 80pg and LAMP amplicons were
      detected within 40min; thereby suggesting a potential applicability of LAMP as a
      sensitive and urgent diagnostic method. Furthermore, positive LAMP reaction was
      directly detected with the naked-eye by monitoring the formation of a white
      precipitate or the color change induced by hydroxy naphthol blue (HNB) dye.
      Finally, 56 clinical isolates were successfully tested for the presence of vanA
      gene by LAMP, which was determined to be more sensitive than PCR. Together, our
      results clearly demonstrate the usefulness of LAMP for the diagnosis of VRE
      infection. 

PMID- 24925602
TI  - Identification of bacteria pathogenic to or associated with onion (Allium cepa)
      based on sequence differences in a portion of the conserved gyrase B gene.
AB  - We have developed a method for the identification of Gram-negative bacteria,
      particularly members of the Enterobacteriaceae, based on sequence variation in a
      portion of the gyrB gene. Thus, we identified, in most cases to species level,
      over 1000 isolates from onion bulbs and leaves and soil in which onions were
      grown. 

PMID- 24925603
TI  - Cyclooxygenase-2 expression in pigs infected experimentally with Mycoplasma
      hyopneumoniae.
AB  - Porcine enzootic pneumonia, primarily caused by Mycoplasma hyopneumoniae (Mh), is
      a contagious disease characterized by catarrhal bronchointerstitial pneumonia.
      Previous studies have evaluated immunohistochemically the distribution of Mh,
      different cellular populations and cytokines during Mh-induced pneumonia.
      Cyclooxygenase (COX)-2 is overexpressed during inflammatory responses by
      different cell types in the lung. The aim of this study was to elucidate the
      possible role of COX-2 in the pathogenesis of porcine enzootic pneumonia. COX-2
      protein was detected by immunohistochemistry in formalin-fixed, paraffin wax
      embedded lung tissues from 10 pigs infected experimentally with Mh. Ten pigs were
      inoculated intranasally with Mh and killed in pairs weekly from 1 to 5 weeks post
      inoculation. Three Mh-free pigs were taken as controls. Bronchial and bronchiolar
      epithelial cells, bronchial submucosal glands and a small number of macrophages
      in the bronchoalveolar exudate expressed COX-2. COX-2 protein was always
      associated with areas of pneumonia and expression was minimal in lungs from
      control pigs. These results suggest that COX-2 plays a role in the pathogenesis
      of Mh-infection.

PMID- 24925604
TI  - BDNF Val66Met polymorphism in primary adult-onset dystonia: a case-control study
      and meta-analysis.
AB  - BACKGROUND: A polymorphism in brain-derived neurotrophic factor (BDNF) (Val66Met)
      has been reported as a risk factor in primary dystonia. However, overall the
      results have been inconclusive. Our aim was to clarify the association of
      Val66Met with primary dystonia, and with the most prevalent clinical subtypes,
      cervical dystonia and blepharospasm. METHODS: We conducted a Spanish multicenter
      case-control study (including 680 primary dystonia patients and 788 healthy
      controls) and performed a meta-analysis integrating our study and six previously
      published studies (including a total of 1,936 primary dystonia patients and 2,519
      healthy controls). RESULTS: We found no allelic or genotypic association with
      primary dystonia, cervical dystonia, or blepharospasm risks, for the allele A
      (Met) from a BDNF Val66Met polymorphism in our case-control study. This was
      confirmed by results from our meta-analysis in white and mixed ethnic populations
      in any genetic model. CONCLUSION: We did not find any evidence supporting the
      association of the BDNF Val66Met polymorphism with primary dystonia.

PMID- 24925605
TI  - Chocolate frogs do not increase completion of parent survey: randomised study.
AB  - Four months into a year-long, national survey assessing parents' experiences of a
      child's diagnosis of autism spectrum disorder, our response fraction was only
      23%. We aimed to determine whether including a chocolate incentive in the postal
      survey would increase the response fraction. Families enrolled between 15 March
      and 25 May 2012 were randomised to receive a chocolate frog versus no chocolate
      frog. Both groups received a written reminder and replacement survey 2 weeks
      after the survey was posted and up to two telephone reminders thereafter. We
      analysed the effect of the incentive using chi(2) tests for the categorical
      response variable and t-tests for the continuous reminder and length of response
      variables at the end of (i) randomisation and (ii) the study (1 November 2012). A
      total of 137 families were randomised in the 6-week period. Parents who received
      an incentive were more likely to return a completed survey in the 6 weeks than
      those who did not (21% vs. 6%, P = 0.009). This effect faded by the end of the
      study (53% vs. 42%, P = 0.4). There were no differences between groups at either
      follow-up in the number of reminders that parents received or the number of days
      it took parents to return the survey. Including a chocolate-based incentive does
      not significantly increase response rate in a postal survey over and above
      standard reminder techniques like posting follow-up survey packs or phoning
      families. 

PMID- 24925607
TI  - Shifting of undernutrition to overnutrition and its determinants among women of
      reproductive ages in the 36 low to medium income countries.
AB  - OBJECTIVE: Objectives are to examine the shift away from undernutrition towards
      overnutrition for low to medium income countries (LMIC) and investigate the
      potential determinants of this shift using the nationally representative survey
      data. DESIGN AND SUBJECTS: We analysed cross-sectional, representative samples of
      540,290 women aged 20-49 years drawn from the Demographic and Health Surveys
      (DHS) at two time points in 36 LMIC. The ratio of overweight-to-underweight at
      earliest and latest survey was calculated for each country to illustrate the
      relative magnitude of the shifting of underweight to overweight. Potential
      determinants of underweight (BMI < 18.5) and overweight (BMI >= 25) were
      examined. RESULTS: In the latest DHS compared to the earliest DHS (mean duration
      10 years), the prevalence of underweight significantly declined for one in two
      countries and the prevalence of overweight significantly increased for 80% of the
      listed countries. The annual increase of overweight was two folds higher than
      annual decline of underweight (6.4% vs. 3.3%). Although higher socio-demographic
      factors were associated with shifting of underweight towards overweight, over
      time, the risk of the highly educated, wealthy, and urban women being overweight
      was weakening. CONCLUSIONS: Findings of this study suggest that among women of
      child-bearing age there was a large shift away from undernutrition to
      overnutrition for most of the LMIC. Overtime, the contribution of higher
      education, wealth and urbanisation to being overweight was decreasing in the
      LMIC.

PMID- 24925606
TI  - Antipsychotic-induced parkinsonism is associated with working memory deficits in
      schizophrenia-spectrum disorders.
AB  - In view of the significant cognitive deficits in schizophrenia and their impact
      on patients' social and occupational functioning, and considering that the
      influence potential influence of antipsychotic-induced extrapyramidal symptoms on
      cognition in schizophrenia remains poorly understood, the current study sought to
      identify the clinical, socio-demographic and neurologic predictors of the
      cognitive performance of schizophrenia patients. Eighty-two schizophrenia
      spectrum (DSM-IV criteria) outpatients were recruited. Psychiatric symptoms were
      evaluated with the Positive And Negative Syndrome Scale and the Calgary
      Depression Scale for Schizophrenia. Extrapyramidal symptoms were evaluated with
      the Extrapyramidal Symptoms Rating Scale, while spatial working, planning
      abilities and visual paired associates learning were evaluated with the CAmbridge
      Neuropsychological Tests Automated Battery. The Stroop test was also
      administered. Multivariate hierarchic linear regression analyses were performed.
      We found that negative symptoms were associated with cognitive flexibility,
      planning, visual learning and working memory performance in schizophrenia. Age,
      sex, number of hospitalizations and antipsychotic type also emerged as
      significant predictors. More importantly, we found a significant association
      between antipsychotic-induced parkinsonism and working memory performance. The
      fact that negative symptoms and socio-demographic variables predicted cognitive
      performance in schizophrenia is consistent with the previous literature on the
      topic. The finding of an association between parkinsonism and working memory may
      have clinical implications, since working memory deficits are considered putative
      endophenotypes of schizophrenia and are known to impair patients' social and
      occupational functioning. Our results will need to be replicated in longitudinal
      studies involving larger samples of patients. 

PMID- 24925608
TI  - Colour perception in cows.
AB  - Cows of the Lowland Black-and-White breed were studied by the method of
      discrimination conditioning according to the differentiation of seven colours in
      Oswald's scale (yellow no. 2, pink no. 5, red no. 7, violet no. 12, blue no. 15,
      green no. 21 and yellowish-green no. 23) from 16 shades of grey in Hering's
      scale. The high percentage of choices made leads to the conclusion that cows see
      colours as distinct entities. It was found from the percentage of positive
      reactions obtained to a given colour that a sequence exists in the cows'
      differentiation of colours. In connection with this the relativelability to
      distinguish the different colours listed above was established and estimated
      statistically (by t-test). Emphasis has also been laid on ethological variations
      with respect to differences in temperament and social status of the cows and the
      result of colour differentiation learning. 

PMID- 24925609
TI  - Memory of a choice direction in a T maze as measured by spontaneous alternation
      in mice: Effects of intertrial interval and reward.
AB  - Spontaneous alternation in a T maze was studied as a one trial learning paradigm
      in mice of the BALB/c strain. In the first experiment the combined effects of
      time interval between the first and second trial (intertrial interval: ITI), food
      deprivation and feeding given during the first trial, were shown to affect
      performance. Thus, on the one hand, the percentage of spontaneous alternation
      decreased as ITI increased; on the other hand, food reward dramatically improved
      spontaneous alternation for the 24-h ITI, but had no significant effect for 30
      sec and 1-h ITI. Since the effect of feeding might be due either to an increase
      of arousal, thus favoring input of informations associated with the first choice,
      or to an improvement in memory consolidation, a second experiment was aimed at
      testing the effect of food given after the first trial. It was shown that, as in
      the first experiment, post-trial feeding improved spontaneous alternation on the
      second trial given 24 hours later with a temporal gradient of effect less than 30
      min. These results clearly showed that the reinforcement of run to one side
      (first trial) increased the tendency to go to the other side 24 hours later. It
      is concluded that reinforcement might have two distinct effects: (i) according to
      SR theory, reinforcement increases conditioned responses and (ii), as shown here,
      acts on memory processes by preventing memory traces from fading. The fact that
      this last effect was only observed for long ITI suggests that short-term or
      transient memory and long-term memory are two relatively independent processes. 

PMID- 24925610
TI  - Correlations between meals and inter-meal intervals in Japanese quail and their
      significance in the control of feeding.
AB  - Significant correlations (P<0.05) between meals and preceding intervals were
      shown more often by Japanese quail when fed on diluted mash (40% cellulose) than
      with undiluted mash or pellets. They showed significant correlations between
      meals and succeeding intervals with about the same frequency on all three foods.
      Most of the correlation coefficients were low, but experiments in which interval
      length and meal size were manipulated artificially confirmed that close
      relationships between meals and intervals can occur, and appear to verify the
      existence of short-term hunger and satiety mechanisms. Possible explanations for
      the low correlation coefficients shown by several bird species are discussed, and
      it is concluded that meal-eating is controlled by a very flexible system. There
      is no evidence that the timing of meals depends on fixed set points, and it is
      suggested instead that degrees of hunger and satiety may determine the
      probabilities of a meal starting or stopping, such a system being associated with
      emptying and filling of parts of the digestive tract. 

PMID- 24925611
TI  - A comparison of the effects of social rearing and social training on approach
      responding of Gallus chicks.
AB  - It has been shown in an earlier paper that chicks that were housed and trained in
      pairs demonstrated a greater resistance to extinction of the neonatal approach
      response than did chicks that were housed and trained in isolation. The purpose
      of the present study was to attempt to replicate these results and to determine
      whether housing or training is the more important factor in generating the
      previous finding. Eighty-three, white Leghorn chicks were tested in an experiment
      employing a 2 * 2 factorial design comparing social vs isolate housing and social
      vs isolate imprinting training on resistance to extinction of a socially
      reinforced running response. The data were consistent with the earlier findings
      and also revealed that the housing condition is more important in producing
      subsequent social searching than is the training condition. 

PMID- 24925612
TI  - Sex and strain comparisons of tonic immobility ("Righting time") in the domestic
      fowl and the effects of various methods of induction.
AB  - Tonic immobility was induced in adult laying hens using different methods and
      substrates, factors which have shown great variety of response in previous work.
      The fact that topic immobility was induced in every situation confirms the robust
      nature of this phenomenon. Placing hens on their backs and restraining them in a
      U-shaped wooden cradle covered with cloth was the most reliable and consistent
      method. Not only was the duration of response greatest when this method was used,
      but less handling, with its possible stressful effects, was required to induce
      it. There were no significant differences in the latency to the first head
      movement or in the duration of immobility between adolescent 'T' (Rhode Island
      Red * Light Sussex) and 'S' (White Leghorn) lines but both these characteristics
      were considerably shorter in the 'J' line birds (Brown Leghorn). There were no
      significant sex differences in the duration of tonic immobility but male 'T' and
      'S' line birds showed greater latencies to the first head movement and fewer
      subsequent alert head movements than females. These results are discussed in
      terms of sex and strain differences in fearfulness. The varied nomenclature used
      to describe the immobility reaction is discussed and an alternative term
      "righting time" is proposed. It is further suggested that the immobility response
      consists of an inhibitory and an alert stage. 

PMID- 24925613
TI  - Pair formation and reproductive output in domestic pigeons.
AB  - Mate selection is a conceivable mechanism whereby an animal could increase its
      reproductive success. The present study investigates the relationship between
      mate selection and reproductive output in domestic pigeons. Pairs allowed to form
      spontaneously, in a situation permitting a certain degree of choice, were
      compared with pairs randomly assigned to each other. The prediction was that
      spontaneously formed pairs should on average achieve a better reproductive output
      than pairs randomly formed. In a reproduction test the spontaneously formed pairs
      began egglaying earlier, laid a greater number of eggs and had a larger number of
      fertilized eggs. It is suggested that the difference between the groups affected
      such important reproductive variables that it could have a substantial effect on
      the birds reproductive success. 

PMID- 24925614
TI  - Effects of female behavior on wing display and courtship of male Drosophila
      simulans and Drosophila melanogaster.
AB  - Corrolations between female rejection behaviors and male wing display were
      calculated for both Drosophila simulans and Drosophila melanogaster intraspicific
      pair-matings. No significant correlations were found for D. melanogaster, but in
      D. simulans flicking by the female appeared to be associated with a shift in male
      wing display pattern resulting in higher levels of vibration. Flicking did not
      appear to discourage courtship by males in either species. 

PMID- 24925623
TI  - (18)F-FDG PET and vascular inflammation: time to refine the paradigm?

PMID- 24925624
TI  - Prognostic value of normal stress myocardial perfusion imaging in diabetic
      patients: a meta-analysis.
AB  - BACKGROUND: The prognostic value of normal stress myocardial perfusion single
      photon emission computed tomography (MPS) in patients with diabetes has only been
      evaluated in single-center studies of relatively limited sample size. We
      performed a meta-analysis of published studies, including diabetic patients with
      known or suspected coronary artery disease (CAD), to assess the predictive value
      for adverse cardiac ischemic events of normal stress MPS. METHODS AND RESULTS:
      Studies published between January 1990 and December 2013 were identified by
      database search. We included studies using stress MPS to evaluate diabetic
      patients with known or suspected CAD and providing data on clinical outcomes of
      non-fatal myocardial infarction or cardiac death with a follow-up time >=12
      months. A total of 14 studies were finally included, recruiting 13,493 patients.
      The negative predictive value (NPV) for non-fatal myocardial infarction and
      cardiac death of normal MPS was 94.92% (95% confidence interval 93.67-96.05),
      during a weighted mean follow-up of 36.24 months, resulting in estimated event
      rate after a negative test equal to 5.08% (95% confidence interval 3.95-6.33).
      The corresponding annualized event rate after a negative test was 1.60% (95%
      confidence interval 1.21-2.04). CONCLUSIONS: Stress MPS has a high NPV for
      adverse cardiac events in diabetic patients with known or suspected CAD leading
      to define a "relatively low-risk" patients category.

PMID- 24925626
TI  - Photocatalytic hydrogen evolution by oleic acid-capped CdS, CdSe, and
      CdS0.75Se0.25 alloy nanocrystals.
AB  - Photocatalytic generation of hydrogen by using oleic acid-capped CdS, CdSe, and
      CdS(0.75)Se(0.25) alloy nanocrystals (quantum dots) has been investigated under
      visible-light irradiation by employing Na(2)S and Na(2)SO(3) as hole scavengers.
      Highly photostable CdS(0.75)Se(0.25) alloy nanocrystals gave the highest hydrogen
      evolution rate (1466 MUmol h(-1) g(-1)), which was about three times higher than
      that of CdS and seven times higher than that of CdSe.

PMID- 24925627
TI  - What would happen to education if we take education evidence seriously?
AB  - Educational practice and educational research are not aligned with each other.
      Current educational practice heavily relies on information transmission or
      content delivery to learners. Yet evidence shows that delivery is only a minor
      part of learning. To illustrate the directions we might take to find better
      educational strategies, six areas of educational evidence are briefly reviewed.
      The flipped classroom idea is proposed to shift our expenditure and focus in
      education. All information delivery could be web distributed, thus creating more
      time for other more expensive educational strategies to support the learner. In
      research our focus should shift from comparing one curriculum to the other, to
      research that explains why things work in education and under which conditions.
      This may generate ideas for creative designers to develop new educational
      strategies. These best practices should be shared and further researched. At the
      same time attention should be paid to implementation and the realization that
      teachers learn in a way very similar to the people they teach. If we take the
      evidence seriously, our educational practice will look quite different to the way
      it does now. 

PMID- 24925628
TI  - The controversy over the minimum quantum requirement for oxygen evolution.
AB  - During the early- to mid-twentieth century, a bitter controversy raged among
      researchers on photosynthesis regarding the minimum number of light quanta
      required for the evolution of one molecule of oxygen. From 1923 until his death
      in 1970, Otto Warburg insisted that this value was about three or four quanta.
      Beginning in the late 1930s, Robert Emerson and others on the opposing side
      consistently obtained a value of 8-12 quanta. Warburg changed the protocols of
      his experiments, sometimes in unexplained ways, yet he almost always arrived at a
      value of four or less, except eight in carbonate/bicarbonate buffer, which he
      dismissed as "unphysiological". This paper is largely an abbreviated form of the
      detailed story on the minimum quantum requirement of photosynthesis, as told by
      Nickelsen and Govindjee (The maximum quantum yield controversy: Otto Warburg and
      the "Midwest-Gang", 2011); we provide here a scientific thread, leaving out the
      voluminous private correspondence among the principal players that Nickelsen and
      Govindjee (2011) examined in conjunction with their analysis of the principals'
      published papers. We explore the development and course of the controversy and
      the ultimate resolution in favor of Emerson's result as the phenomenon of the two
      light-reaction, two-pigment-system scheme of photosynthesis came to be
      understood. In addition, we include a brief discussion of the discovery by Otto
      Warburg of the requirement for bicarbonate in the Hill reaction. 

PMID- 24925629
TI  - Aortopathy in Marfan syndrome: an update.
AB  - Marfan syndrome (MFS) is an inherited autosomal dominant multisystem disease
      caused by mutations in the FBN1 gene encoding fibrillin-1, an extracellular
      matrix glycoprotein widely distributed in mesenchymal-derived tissues that
      provide a scaffold for elastin deposition. MFS is characterized by variable
      clinical manifestations, including skeletal, ocular, and cardiovascular
      abnormalities; ascending aortic aneurysm with ensuing dissection and rupture is
      the main life-threatening cardiovascular manifestation of MFS. Histological
      aspects of MFS aortopathy include a medial degeneration from disarray and
      fragmentation of elastic fibers and accumulation of basophilic ground substance
      areas depleted of smooth muscle cells (SMCs). Transmission electron microscopy
      well evidences the high number of interruptions and the thick appearance of the
      elastic lamellae and the accumulation of abundant extracellular glycosaminoglycan
      rich material, sometimes SMCs showing a prevalent synthetic phenotype. The
      aberrant signaling of transforming growth factor-beta (TGF-beta) as the
      consequence of the altered structure of fibrillin-1 induces activation and the
      overexpression of Smad-dependent profibrotic signaling pathway and ERK1/2
      mediated increased synthesis of matrix metalloproteinases. In addition, MFS is
      accompanied by an impaired aortic contractile function and aortic endothelial
      dependent relaxation, which is caused by an enhancement of the oxidative stress
      and increased reactive oxygen species during the progression of the disease. Many
      studies are currently evaluating the contribution of TGF-beta-mediated
      biomolecular pathways to the progression of MFS aortopathy and aneurysm
      development, in order to discover new targets for pharmacological strategies
      aimed to counteract aortic dilation. 

PMID- 24925630
TI  - Pheromonal control: reconciling physiological mechanism with signalling theory.
AB  - Pheromones are intraspecific chemical signals. They can have profound effects on
      the behaviour and/or physiology of the receiver, and it is still common to hear
      pheromones described as controlling of the behaviour of the receiver. The
      discussion of pheromonal control arose initially from a close association between
      hormones and pheromones in the comparative physiological literature, but the
      concept of a controlling pheromone is at odds with contemporary signal evolution
      theory, which predicts that a manipulative pheromonal signal negatively affecting
      the receiver's fitness should not be stable over evolutionary time. Here we
      discuss the meaning of pheromonal control, and the ecological circumstances by
      which it might be supported. We argue that in discussing pheromonal control it is
      important to differentiate between control applied to the effects of a pheromone
      on a receiver's physiology (proximate control), and control applied to the
      effects of a pheromone on a receiver's fitness (ultimate control). Critically, a
      pheromone signal affecting change in the receiver's behaviour or physiology need
      not necessarily manipulate the fitness of a receiver. In cases where pheromonal
      signalling does lead to a reduction in the fitness of the receiver, the
      signalling system would be stable if the pheromone were an honest signal of a
      social environment that disadvantages the receiver, and the physiological and
      behavioural changes observed in the receiver were an adaptive response to the new
      social circumstances communicated by the pheromone. 

PMID- 24925631
TI  - Video presentation of the second stage of a two-stage repair for proximal
      hypospadias: a safe and reproducible technique.
AB  - OBJECTIVE: The aims of proximal hypospadias repair are good cosmetic outcomes
      with low rates of complication, with a low number of operative exposures, before
      the age of genital difference realisation. Neo-urethral fistula and stenosis are
      well recognised complications; with international rates of 3.8-16% and 1.3-15.6%
      respectively. We present the key steps of the second of a two staged repair in
      video format. METHOD: Video recording of the procedure performed on an 18-month
      old with mid-penile hypospadias is presented. The steps are described; the
      importance of tension free tubularisation, layered urethral closure, suture
      technique, vascularised prepucal graft technique, optimal glanuloplasty, and
      penile shaft skin repair are highlighted. RESULT: The child was brought back to
      the day ward for catheter removal at 7 days; follow-up in clinic showed good
      postoperative appearance. This technique has been performed on 31 boys with a
      fistula rate and stenosis rate favourable to the literature. CONCLUSION: We
      demonstrate a two-stage technique by video format for proximal hypospadias which
      is reproducible and gives results comparable to the literature.

PMID- 24925632
TI  - Circumcision on the web: a comparison of quality, content, and bias online.
AB  - OBJECTIVE: In 2012, the American Academy of Pediatrics (AAP) newborn circumcision
      policy statement expressed that although benefits outweigh risks, final decisions
      lie with parents. Although health information on the Internet is plentiful, the
      quality and availability of information on circumcision, including dissemination
      of AAP and AUA policy statements, is unknown. We analyzed English and Spanish
      circumcision websites to evaluate their overall quality, detail, accuracy, and
      bias. METHODS: In April 2013, three search engines were queried for English and
      Spanish circumcision websites, which were analyzed utilizing the DISCERN Plus
      scale for content quality as well as additional study-specific criteria. RESULTS:
      We analyzed 214 websites (141 English, 73 Spanish). Most websites in both
      languages had very good content quality and were neutral regarding circumcision.
      Regardless of language, only 21% of sites mentioned the updated AAP guidelines.
      Surprisingly, the AUA circumcision policy statement did not appear in the top
      results. Spanish sites were more likely to give good descriptions of circumcision
      procedures than English sites (p < 0.04), less likely to cite sources (p < 0.01),
      and more likely to describe benefits (p = 0.02).. CONCLUSIONS: Newborn
      circumcision information on the Internet is of very good quality, but different
      English and Spanish characteristics possibly reflect cultural bias, which may
      explain the disparate rates of circumcision between different groups in the USA.
      The AAP's circumcision policy statement was referenced by a minority (20%) of
      websites, and AUA's policy statement was not even part of the top results. The
      AUA should have a more active role in providing accurate and comprehensive online
      information to parents regarding circumcision.

PMID- 24925633
TI  - Decreased "ineffective erythropoiesis" preserves polycythemia in mice under long
      term hypoxia.
AB  - Hypoxia induces innumerable changes in humans and other animals, including an
      increase in peripheral red blood cells (polycythemia) caused by the activation of
      erythropoiesis mediated by increased erythropoietin (EPO) production. However,
      the elevation of EPO is limited and levels return to normal ranges under normoxia
      within 5-7 days of exposure to hypoxia, whereas polycythemia continues for as
      long as hypoxia persists. We investigated erythropoiesis in bone marrow and
      spleens from mouse models of long-term normobaric hypoxia (10 % O2) to clarify
      the mechanism of prolonged polycythemia in chronic hypoxia. The numbers of
      erythroid colony-forming units (CFU-E) in the spleen remarkably increased along
      with elevated serum EPO levels indicating the activation of erythropoiesis during
      the first 7 days of hypoxia. After 14 days of hypoxia, the numbers of CFU-E
      returned to normoxic levels, whereas polycythemia persisted for >140 days. Flow
      cytometry revealed a prolonged increase in the numbers of TER119-positive cells
      (erythroid cells derived from pro-erythroblasts through mature erythrocyte
      stages), especially the TER119 (high) CD71 (high) population, in bone marrow. The
      numbers of annexin-V-positive cells among the TER119-positive cells particularly
      declined under chronic hypoxia, suggesting that the numbers of apoptotic cells
      decrease during erythroid cell maturation. Furthermore, RT-PCR analysis showed
      that the RNA expression of BMP-4 and stem cell factor that reduces apoptotic
      changes during erythroid cell proliferation and maturation was increased in bone
      marrow under hypoxia. These findings indicated that decreased apoptosis of
      erythroid cells during erythropoiesis contributes to polycythemia in mice during
      chronic exposure to long-term hypoxia.

PMID- 24925634
TI  - TRB3 mediates renal tubular cell apoptosis associated with proteinuria.
AB  - Proteinuria may contribute to progressive renal damage by inducing
      tubulointerstitial inflammation, fibrosis and tubular cell apoptosis, but the
      underlying mechanisms remain largely unknown. TRB3 is a kinase-like molecule that
      can modify cellular survival and interfere with signal transduction pathways. We
      seek to determine the role of TRB3 in renal tubular cell apoptosis associated
      with proteinuria. Herein, we reported that in a rat tubular cell line, high
      concentration of albumin augmented TRB3 expression and induced apoptosis, while
      TRB3 silencing with special small interference RNA significantly attenuated
      apoptosis. In addition, we found that albumin-induced apoptosis was related to
      inhibition of Akt phosphorylation, which was, however, partially reversed by TRB3
      silencing, indicating that TRB3 worked through Akt pathway in this apoptotic
      signaling cascade. In vivo, we observed increased TRB3 expression in kidneys of
      streptozotocin-induced diabetic nephropathy model and albumin-overload
      nephropathy model, both of which showed overt proteinuria. Notably, proteinuria
      induced apoptosis in renal tubules, which was less severe after genetically
      inhibition of TRB3. Taken together, these results suggest that TRB3 mediates
      renal tubular cell apoptosis induced by protein overload, broadening our
      understanding of the pathogenesis of progressive proteinuric kidney diseases.

PMID- 24925635
TI  - Nucleophosmin1 associated with drug resistance and recurrence of bladder cancer.
AB  - Drug resistance and recurrence are the major obstacles to bladder cancer
      chemotherapy. Our laboratory had reported that nucleophosmin1 was one of the
      differentially expressed proteins between bladder cancer cell lines PUMC-91 and
      PUMC-91/1.0ADM based on 2D-PAGE proteomics approaches. In this study, we want to
      explore the relationship among nucleophosmin1, drug resistance, and recurrence of
      bladder cancer, using normal bladder epithelia cell line SV-HUC-1, bladder cancer
      cell lines PUMC-91, PUMC-91 against gradient doses of adriamycin (0.3, 0.6, and
      1.0 MUg/ml), and bladder cancer tissue samples. The bladder cancer tissue samples
      were divided into two groups according to the interval of recurrence (<6 months
      and >2 years). The differences were detected by Western blotting and
      immunohistochemistry. The protein of nucleophosmin1 was differentially expressed
      with each other in SV-HUC-1, PUMC-91, PUMC-91/0.3ADM, and PUMC-91/1.0ADM (p <
      0.05). Nucleophosmin1 was less expressed in later recurring (>2 years) bladder
      cancer tissue samples compared with samples that recurred <6 months (p = 0.035).
      The expression of nucleophosmin1 was independently associated with gradient drug
      resistance and recurrent frequency of bladder cancer. Nucleophosmin1 was a key
      regulator in either a drug-resistant bladder cancer or bladder cancer recurrence
      model. It may be possible to think nucleophosmin1 can provide more helpful
      information for clinical drug treatment of bladder cancer patients and frequently
      recurred ones. 

PMID- 24925636
TI  - TSH levels are associated with vitamin D status and seasonality in an adult
      population of euthyroid adults.
AB  - A circannual periodicity in thyrotropin (TSH) secretion has been reported but the
      causes of these phenomenon are still undefined. Vitamin D exerts a direct
      influence on pituitary axes including the hypothalamus-pituitary-thyroid axis.
      Aims of the present study were to investigate the presence of a seasonal
      variability of TSH secretion and to study the association between vitamin D
      status and TSH levels in a population of euthyroid adults. For this purpose, we
      recruited 294 euthyroid adults (M/F 133/161, 48.5 +/- 12.4 years). Study
      participants underwent clinical examination and routine biochemistry assessment.
      Vitamin D deficiency was diagnosed for serum 25(OH) vitamin D <25 nmol/l.
      Significantly higher TSH levels were found in subjects who underwent blood
      sampling during the Autumn-Winter compared with individuals evaluated in Spring
      Summer (2.3 +/- 1.3 vs. 1.8 +/- 1.1 MUIU/ml, p = 0.03). Vitamin D deficiency was
      strongly associated with higher TSH levels (p = 0.01) after adjusting for sex,
      age, and sample's season. Although vitamin D deficiency was also associated with
      metabolic syndrome and its components, the association between TSH levels and
      vitamin D status persisted also considering these confounders. These data reveal
      the occurrence of seasonal variability of serum TSH concentration in euthyroid
      subjects and provide evidence for the first time that an association exists
      between vitamin D status and serum TSH levels. 

PMID- 24925637
TI  - Effects of interleukin-10 gene deficiency on hepatic biochemical metabolism in
      mice.
AB  - The aim of this study was to investigate the effect of interleukin-10 (IL-10)
      gene deficiency on mouse liver function. The experimental mice were divided into
      wild-type and IL-10 knockout groups. Serological biomarkers for liver functions
      were detected by the automatic biochemical analyzer AU5400. The pathological
      changes were assessed by the light microscope. The levels of inducible nitric
      oxide synthase (iNOS) and interleukin-1beta (IL-1beta) in liver tissues were
      determined by quantitative real-time PCR and enzyme-linked immunosorbent assay.
      Compared with the wild type, the serum levels of albumin (ALB), total protein,
      total bilirubin and direct bilirubin in IL-10-deficient mice were significantly
      decreased (P < 0.05). No obvious pathological changes including liver necrosis
      and inflammatory cell infiltration were found. The expression of iNOS and IL
      1beta genes, the serum levels of iNOS and IL-1beta were significantly higher in
      IL-10-deficient mice than in wild-type mice (P < 0.05). The absence of IL-10 gene
      can significantly decrease serum ALB and bilirubin. The effect may be related to
      the upregulation of iNOS and IL-1beta. 

PMID- 24925638
TI  - Leukotriene enhanced allergic lung inflammation through induction of chemokine
      production.
AB  - The leukotrienes (LTs) enhance allergen- and interleukin (IL)-13-dependent
      allergic lung inflammatory disease. However, the precise requirement of LTs and
      the mechanism by which they elicit allergic lung responses remain uncertain. To
      clarify the involvement of LTs in respiratory allergen- and IL-13-induced
      experimental asthma and elucidate the underlying mechanisms of LTs-mediated
      enhanced allergic asthma, we investigated the role of LTs in two models of
      allergic inflammation: intranasal Aspergillus protease allergen and recombinant
      IL-13-induced T helper type 2 (Th2) cell-mediated inflammation, and also examined
      Th2-related chemokines downstream of LTs signaling. 5-Lipoxygenase (5-LO)
      deficient mice exposed to short-term intranasal Aspergillus protease allergen
      showed attenuated airway inflammation, decreased airway hyper-responsiveness and
      reduced bronchoalveolar eosinophilia when compared to wild-type mice. However,
      this phenotype was less apparent using long exposure to the same allergen. 5-LO
      deficient mice exposed to intranasal rIL-13 also showed attenuated phenotypes of
      allergic asthma via significant reduction in Th2-specific chemokines, CCL7 and
      CCL17 production and decreased Th2 cells recruitment to the lungs. Addition of
      leukotriene B4 (LTB4) and LTC4 to the airways of 5-LO-deficient mice resulted in
      the rescue of rIL-13-induced experimental asthma. Furthermore, LTs addition to
      rIL-13 synergistically enhanced the production of Th2-specific chemokines in the
      lung and inflammatory responses. Therefore, our findings suggest that LTs
      complement allergens and their downstream cytokine (e.g., IL-13) induced Th2
      inflammation by enhancing the induction of Th2 chemokines. 

PMID- 24925639
TI  - LC-MS/MS analysis of plasma polyunsaturated fatty acids in patients with
      homozygous sickle cell disease.
AB  - The aim of this study was to determine circulating omega-6, omega-3
      polyunsaturated fatty acids and prostaglandin E2 (PGE2) levels in steady state
      sickle cell disease (SCD) patients. Blood was collected from healthy hemoglobin
      volunteers and steady state homozygous HbSS patients who had not received blood
      transfusions in the last 3 months. Plasma levels of arachidonic acid (AA, C20:4n
      6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA,
      C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) were determined by an
      optimized multiple reaction monitoring method using ultrafast liquid
      chromatography coupled with tandem mass spectrometry. PGE2 was measured in serum
      samples by enzyme immunoassay. Plasma AA and DGLA were significantly increased
      while EPA and DHA were significantly decreased in SCD plasma compared to control.
      Serum PGE2 levels, AA/DHA and AA/EPA ratio was significantly higher in SCD
      patients when compared to control group. The significant increase in PGE2 levels,
      AA/EPA and AA/DHA ratio confirms the presence of a proinflammatory state in SCD
      patients. 

PMID- 24925640
TI  - Telomere length in non-neoplastic colonic mucosa in ulcerative colitis (UC) and
      its relationship to the severe clinical phenotypes.
AB  - Telomere shortening occurs with human aging in many organs and tissues and is
      accelerated by rapid cell turnover and oxidative injury. To clarify the clinical
      importance of telomere shortening in colonic mucosa in ulcerative colitis (UC),
      we measured average telomere length using quantitative real-time PCR in non
      neoplastic colonic mucosa in UC patients and assessed its relationship to various
      clinical subtypes. Relative telomere length in genomic DNA was measured in
      colonic biopsies obtained from rectal inflammatory mucosa from 86 UC patients as
      well as paired non-inflammatory proximal colonic mucosae from 10 patients. Data
      were correlated with various clinical phenotypes. In paired samples, average
      relative telomere length of rectal inflammatory mucosa was shortened compared to
      normal appearing proximal colon in eight out of ten cases (p = 0.01). Telomere
      length shortening was significantly associated with more severe Mayo endoscopic
      subscore (p < 0.0001) and cases needing surgery due to toxic megacolon or cancer
      occurrence (p = 0.043). When the severe clinical phenotype was defined as having
      at least one of following phenotypes, more than two times of hospitalization,
      highest Mayo endoscopic subscore, steroid dependent, refractory, or needing
      operation, average relative telomere length was significantly shortened in the
      same phenotypes than the others (p = 0.003). Telomere shortening is associated
      with more severe clinical phenotypes of UC, reflecting severe inflammatory state
      in the colonic mucosa. 

PMID- 24925641
TI  - Influencial factors of the performance of interferon-gamma release assays in the
      diagnosis of childhood tuberculosis.
AB  - Diagnosis of active tuberculosis (TB) in children remains difficult. This study
      aimed at evaluating the ability of interferon-gamma release assays (IGRAs) in the
      detection of active TB in human immunodeficiency virus-negative children
      vaccinated with Bacille Calmette-Guerin and investigating the effect of
      prednisolone treatment on the IGRAs performance. Among the 162 children with
      suspected TB disease recruited in China, 60 were tested with QuantiFERON-TB Gold
      In Tube (QFT-GIT) and 102 were tested with T-SPOT.TB. QFT-GIT presented a
      sensitivity of 83.9 % (95 % CI 66.9-93.4 %) and a specificity of 88.5 % (95 % CI
      70.2-96.8 %), while T-SPOT.TB had a sensitivity of 75.9 % (95 % CI 63.4-85.2 %)
      and a specificity of 94.7 % (95 % CI 81.8-99.5 %). The positive predictive value
      was high in both assays, 92.9 % for QFT-GIT and 95.7 % for T-SPOT.TB. In total of
      these two kinds of IGRAs, false negative rate was significantly higher in
      children receiving systemic prednisolone (1 mg/kg/day) therapy for >1 week (two
      tested with T-SPOT.TB and five tested with QFT-GIT) than in those with <=1 week
      of prednisolone therapy and without prednisolone therapy (57.1 vs. 18.3 %, p =
      0.035). There was no significant difference of the positive rate of both tests in
      children <5 years old compared with those >=5 years old. Both types of IGRAs
      showed good diagnostic values in detecting childhood TB before microbiological
      evidence was available. Glucocorticoids had a significant negative influence on
      IGRAs if treated for >1 week. Age made no difference on the performance of these
      tests in children. 

PMID- 24925643
TI  - Soluble expression of human glycoprotein Ibalpha in Escherichia coli through
      replacement of the N-terminal capping domain.
AB  - Glycoprotein Ibalpha (GpIbalpha), a family of LRR (leucine-rich repeat) proteins,
      is a membrane protein on the platelet, and plays an important role in
      atherothrombotic events. The complex formation of GpIbalpha with the von
      Willebrand Factor (vWF) has been revealed to lead to acute coronary syndrome
      (ACS) or stroke. A considerable attention has been paid to understand the
      biological functions of GpIbalpha and its regulation. However, difficulty with
      the soluble expression of human GpIbalpha in bacteria has hampered the relevant
      research. Herein, we present a soluble expression of GpIbalpha in Escherichiacoli
      by replacing the N-terminal capping domain of GpIbalpha with that of Internalin B
      using a computational approach. The resulting protein was expressed as a soluble
      form in E. coli, maintaining its structural feature and binding property for vWF.
      The present approach can be broadly used for the soluble expression of human LRR
      proteins in E. coli.

PMID- 24925642
TI  - Effects of chronic hepatitis C genotype 1 and 4 on serum activins and follistatin
      in treatment naive patients and their correlations with interleukin-6, tumour
      necrosis factor-alpha, viral load and liver damage.
AB  - The importance of activins and follistatin in liver diseases has recently
      emerged. The aim of the present study was to measure the influence of chronic
      infection with viral hepatitis C (CHC) genotype 1 and 4 on serum levels of
      activin-A, activin-B and follistatin, and to determine their correlations with
      viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)
      alpha. Sera samples collected from 20 male and 20 female treatment naive CHC
      genotype 1 and 4 Saudi patients (ten males and ten females for each genotype),
      and 40 gender- and age-matched healthy participants were analysed for activin-A,
      activin-B and follistatin using enzyme-linked immunosorbent assay and their
      levels were correlated with IL-6, TNF-alpha, viral load and AST platelet ratio
      index (APRI). Serum activin-A, activin-B, IL-6 and TNF-alpha were significantly
      increased, while serum follistatin was significantly decreased, in both genders
      of CHC patients compared with control subjects, In both viral genotypes, activin
      A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF
      alpha, and negatively with albumin (P < 0.01). Activin-B showed the same
      correlations of activin-A only in CHC genotype 1 patients, but it was weaker than
      activin-A. No correlation was detected with follistatin. Serum activins,
      particularly activin-A, and follistatin are significantly altered by CHC genotype
      1 and 4. This dysregulation of activins/follistatin axis may be associated with
      viral replication, host immune response and liver injury. Further studies are
      needed to illustrate the definite role(s) and clinical value of activins and
      follistatin in CHC. 

PMID- 24925644
TI  - Over-expression in E. coli and purification of functional full-length murine
      small C-terminal domain phosphatase (SCP1, or Golli-interacting protein).
AB  - During myelination in the central nervous system, proteins arising from the gene
      in the oligodendrocyte lineage (golli) participate in diverse events in signal
      transduction and gene regulation. One of the interacting partners of the Golli
      isoform BG21 was discovered by yeast-2-hybrid means and was denoted the Golli
      interacting-protein (GIP). In subsequent in vitro studies of recombinant murine
      GIP, it was not possible to produce a full-length version of recombinant murine
      rmGIP in functional form under native conditions, primarily because of solubility
      issues, necessitating the study of a hexahistidine-tagged, truncated form DeltaN
      rmGIP. This protein is an acidic phosphatase belonging to the family of RNA
      polymerase-2, small-subunit, C-terminal phosphatases (SCP1), and studies of the
      human ortholog hSCP1 have also been performed on truncated forms. Here, a new
      SUMO-expression and purification protocol has been developed for the preparation
      of a functional, full-length mSCP1/GIP (our nomenclature henceforth), with no
      additional purification tags. Both full-length mSCP1/GIP and the truncated murine
      form (now denoted DeltaN-rmSCP1/GIP) had similar melting temperatures, indicating
      that the integrity of the catalytic core per se was minimally affected by the N
      terminus. Characterization of mSCP1/GIP activity with the artificial substrate p
      NPP (p-nitrophenylphosphate) yielded kinetic parameters comparable to those of
      DeltaN-rmSCP1/GIP and the truncated human ortholog DeltaN-hSCP1. Similarly,
      mSCP1/GIP dephosphorylated a more natural CTD-peptide substrate (but not protein
      kinase C-phosphorylated BG21) with comparable kinetics to DeltaN-hSCP1. The
      successful production of an active, full-length mSCP1/GIP will enable future
      evaluation of the functional role of its N-terminus in protein-protein
      interactions (e.g., BG21) that regulate its phosphatase activity.

PMID- 24925645
TI  - Expression, purification and refolding of active durum wheat (Triticum durum
      Desf.) secretory phospholipase A2 from inclusion bodies of Escherichia coli.
AB  - Recently, a durum wheat (Triticum durum Desf.) secretory phospholipase A2
      (TdsPLA2III) was identified in leaves as potentially involved in plant responses
      to conditions of limiting water supply. Therefore, to allow future functional
      studies on TdsPLA2III and shed further light on the involvement of sPLA2 isoforms
      in specific plant functions, here we report a protocol for the overexpression of
      TdsPLA2III in Escherichia coli in the form of inclusion bodies, and for its
      purification and refolding. The use of the Gateway system (Invitrogen) allows the
      expression of a large quantity of the mature form (without the signal peptide) of
      TdsPLA2III with an N-terminal 6*His-tag, for purification using Ni-affinity
      chromatography. The purified recombinant 6*His-TdsPLA2III fusion protein is then
      refolded using a step-wise dialysis approach. About 40mg purified and active
      protein was obtained from 1L of cell culture. This recombinant 6*His-TdsPLA2III
      protein shows PLA2 activity, as it can hydrolyze linoleate from the sn-2 position
      of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine. Moreover, it has some
      features that are typical of other known plant sPLA2s: Ca(2+)-dependence,
      inhibition by the disulfide bond reducing agent dithiothreitol, and resistance to
      high temperature.

PMID- 24925647
TI  - Mise en evidence d'effects grand-maternels sur les conduites maternelles de la
      souris.
AB  - Continuous recording of locomotor activity and time spent in the nest were
      performed on mice during the five first days postpartum. We compared mice of the
      C57BL/6 inbred strain to mice of the two reciprocal F2's derived from the C57BL/6
      and BALB/c parental strains. All animals reared foster pups of the C57BL/6
      strain. The results did not show any difference between the three groups for the
      total amount of time spent in the nest ; this parameter decreases with days. No
      difference appeared between the C57BL/6 group and the F2 B6CxCB6 group (having a
      grandmother of the C57BL/6 strain), whereas each of these groups differed
      significantly from F2 CB6xB6C group (having a grandmother of the BALB/c strain)
      for the following indices : locomotor activity, mean duration of a stay in the
      nest, mean duration of an absence from the nest and percentage of nocturnal
      activity. These results are discussed in terms of grandmaternal effects as far as
      the variation in the strain of the grandmother is the only factor which can
      account for these differences in behavior. 

PMID- 24925646
TI  - ERK/Egr-1 signaling pathway is involved in CysLT2 receptor-mediated IL-8
      production in HEK293 cells.
AB  - The CysLT2 receptor is involved in myocardial ischemia/reperfusion injury,
      differentiation of colorectal cancers, bleomycin-induced pulmonary inflammation
      and fibrosis. However, the signal transduction of cysteinyl leukotriene receptor
      2 (CysLT2) in inflammatory responses remains to be clarified. In HEK293 cells
      stably expressing hCysLT1, hCysLT2 and rGPR17, we determined the signaling
      pathways for interleukin-8 (IL-8) production after CysLT2 receptor activation.
      HEK293 cells were stably transfected with the recombinant plasmids of pcDNA3.1(+)
      hCysLT1, pcDNA3.1(+)-hCysLT2 and pcDNA3.1-rGPR17. Leukotriene C4 (LTC4) and LTD4
      were used as the agonists to induce IL-8 production and the related changes in
      signal molecules. We found that LTC4 and LTD4 significantly induced IL-8 promoter
      activation in the HEK293 cells stably expressing hCysLT2, but not in those
      expressing hCysLT1 and rGPR17. In hCysLT2-HEK293 cells, LTC4 induced elevation of
      intracellular calcium, ERK1/2 phosphorylation and Egr-1 expression, and
      stimulated IL-8 expression and release. These responses were blocked by the
      selective CysLT2 receptor antagonist HAMI3379. The ERK1/2 inhibitor U0126
      inhibited Egr-1 and IL-8 expression as well as IL-8 release, but the JNK and p38
      inhibitors did not have the inhibitory effects. Down-regulation of Egr-1 by RNA
      interference with its siRNA inhibited the LTC4-induced IL-8 expression and
      release. In conclusion, these findings indicate the ERK-Egr-1 pathway of CysLT2
      receptors mediates IL-8 production induced by the pro-inflammatory mediators LTC4
      and LTD4. 

PMID- 24925648
TI  - Behavioral contrast in rats when qualitatively different reinforcers are used.
AB  - Behavioral contrast was studied during multiple schedules which provided
      qualitatively different reinforcers in the two components. Five rats responded on
      a baseline schedule in which both components delivered food reinforcers (food
      food), and then on a contrast schedule in which one component delivered food and
      the other delivered water (food-water). Following this, baseline was recovered.
      Five other rats responded on a baseline schedule in which both components
      delivered water reinforcers (water-water), then on a food-water schedule, and
      then on the baseline, water- water, schedule. Contrast was not observed when
      relatively low rates of reinforcement were use but it was sometimes observed when
      high rates of reinforcement were used. The rate of responding for a constant
      water reinforcer decreased when food replaced water in the other component. The
      rate of responding for a constant food reinforcer did not change when a water
      reinforcer replaced food in the other component. These results are similar to
      those reported by Ettinger and McSweeney (1981) when pigeons served as subjects. 

PMID- 24925649
TI  - Self-control choice with electrical stimulation of the brain as a reinforcer.
AB  - In a discrete-trials procedure, rats chose between a small reinforcer (a low
      frequency of electrical stimulation of the brain) and a larger reinforcer (a
      higher frequency of stimulation). The small reinforcer was delivered after a
      delay that was constant within a condition but varied across conditions. The
      delay for the large reinforcer was increased or decreased many times a session in
      order to estimate an indifference point--a delay at which the two alternatives
      were chosen about equally often. When the indifference points from several
      conditions were plotted as a function of the delay for the small reinforcer, the
      resultant "indifference curves" had positive y-intercepts and slopes greater than
      1.0. These results are similar to those obtained in previous studies with pigeons
      as subjects and food as the reinforcer, and they suggest that a hyperbolic
      equation describes the relation between a reinforcer's delay and its value or
      effectiveness. The fact that a large reinforcer delayed several seconds was
      chosen over a small reinforcer delivered almost immediately after a response
      provides further evidence against a simple reciprocal relation between delay and
      value. 

PMID- 24925650
TI  - Total recovery of response to novelty after ectopic pituitary isografts in Snell
      Dwarf mice (dw/dw).
AB  - The effects of ectopic pituitary isografts on response to novelty were studied in
      adult Snell Dwarf mice. Because of anterohypophyseal deficiency, these animals
      exhibit dwarfism, sterility and marked neurochemical and behavioural deficits.
      When given the opportunity to move around freely in simultaneously presented
      novel and familiar environments, grafted dwarf (GRAFT Dw) and sham-grafted
      control (SHAM C) mice showed a significant novelty preference while sham-grafted
      dwarf (SHAM Dw) mice exhibited no preference. Both SHAM C and GRAFT Dw mice
      frequently reared and covered the familiar compartment more quickly than the
      novel compartment, while SHAM Dw mice reared infrequently and covered the two
      compartments at equal speed. These data reveal in the mutant a total indifference
      toward its environment and show a total recovery of neotic behaviour after
      grafting. The literature is very vague concerning the hormonal changes induced
      after ectopic pituitary grafting but subsequent specific hormonal treatments and
      biochemical manipulations would facilitate identification of the hypophyseal
      hormones and/or the growth factors involved in the behavioural changes. 

PMID- 24925651
TI  - Radial maze performance under food and water deprivation.
AB  - The performance of food and water-deprived rats was examined on two eight-arm
      radial mazes. Accurate performance developed rapidly under both deprivation
      conditions. On an open maze, where extra-maze visual cues were readily available,
      water-deprived, but not food-deprived, rats tended to adopt a response strategy
      of choosing adjacent arms. On an enclosed maze, which reduced extra-maze visual
      information, both groups showed this response pattern. Tolman (1948), in
      presenting his "cognitive map" hypothesis to account for the performance of rats
      on spatial problems, suggested that under some conditions animals will utilize
      narrow strip maps rather than broad comprehensive maps. The variables
      establishing these conditions include amount of training, the availability of
      environmental cues, and degree of deprivation. The findings reported here are
      examined in terms of Tolman's cognitive map approach to spatial representation. 

PMID- 24925652
TI  - The effects of inbreeding and ventilation on mating behavior in Drosophila
      pseudoobscura.
AB  - Two outbred and two inbred lines of Drosophila pseudoobscura were used in mating
      behavior studies. For each line, mating rates were compared under both ventilated
      and nonventilated conditions. Under nonventilated conditions courtship and mating
      were earlier, not following a random rate of occurence, and females mated after
      fewer courtships. Flies from inbred lines tended to court and mate earlier. Under
      all conditions a high proportion of matings occured on the first courtship
      attempt. 

PMID- 24925653
TI  - Suppression by reinforcement, a model for multiple-schedule behavioral contrast.
AB  - The present paper argues that multiple-schedule behavioral contrast occurs
      because delayed reinforces suppress behavior. According to this idea, some
      reinforcers delivered in the second component of a multiple schedule suppress
      responding during the first component because they follow that responding after a
      delay. Removing second-component reinforcers removes suppression from the first
      component and response rates rise, creating positive contrast. Adding second
      component reinforcers adds suppression and response rates fall, creating negative
      contrast. The paper shows that this idea is consistent with the major findings in
      the contrast literature. 

PMID- 24925654
TI  - Behavioural dominance: Some elementary probabilistic considerations and their
      behavioural implications.
AB  - Despite near ubiquity of behavioural dominance, its nature and implications
      remain uncertain. Criteria commonly used to detect and assess dominance are not
      easily referred to random expectation, and may be behaviourally inappropriate.
      Use of the final score , Wins to A:Wins to B, is insufficient on both counts, and
      does not consider temporal succession. Successive wins and losses for an
      individual can be scored as positive (p) and negative (q) units, whose sum at any
      encounter is the cumulative score (S). This indicates lead (+S), lag (-S) or
      equality (S=0), sums all prior experience in a single present state, and may then
      be of direct behavioural relevance. Lead so measured is appropriate to assessment
      of the overall direction of dominance, and allows distinction between 'reversals'
      which do or do not alter this. Exact random probabilities of all possible values
      of SN at encounter N, and of all possible win-loss sequences leading to these can
      be specified by reference to the arcsine probability distribution. Calculations
      of such expectations for situations of particular behavioural interest reveal
      counter-intuitively high degrees of consistency in lead (dominance). The need to
      establish reliable null hypotheses to avoid erroneous detection of behavioural
      dominance is stressed. 

PMID- 24925655
TI  - Urine odours and marking patterns in territorial laboratory mice (Mus musculus ).
AB  - Responses of subordinate male mice in an open field, half of which was spotted
      with water and half with urine collected from other males were analysed. Test
      mice avoided the urine of dominant mice which held territories in a "free range"
      room, but not of caged dominants or of singly housed males. They spent more time
      in the urine half of the open field when it was spotted with the urine of free
      range subordinates. Locomotor activity was depressed in the presence of caged
      subordinate urine. The urine marking patterns of the different categories of
      males were investigated in a separate experiment. Subordinate males tend to
      deposit their urine in relatively few large pools mainly at the edge of a test
      arena, whilst dominant and singly-housed animals produce large numbers of tiny
      spots. Dominant animals urine-mark evenly over the entire area, whereas singly
      housed animals mark more intensely at the periphery than at the centre. It is
      concluded that only territorial males produce in their urine a factor that deters
      other (at least subordinate) males from investigating areas marked with it, and
      that they actively distribute it over a wide area. 

PMID- 24925656
TI  - Dissociation of instrumental and Pavlovian contingencies in a discriminated
      instrumental procedure.
AB  - Four pigeons were exposed to an experimental procedure in which the presentation
      of a stimulus at one intelligence panel in a longbox signaled the opportunity to
      obtain response-dependent food contingent upon withdrawal from the stimulus to
      the other end of the box. Four other pigeons in addition received unsignaled,
      response-independent food during the intertrial interval. Both groups of subjects
      learned to withdraw from the stimulus during stimulus presentations, but the
      subjects who received response-independent food during the intertrial interval
      learned to do so faster than the subjects in the other group. Subjects who
      received response-independent food in the absence of the stimulus hardly ever
      contacted the stimulus upon its presentation, whereas subjects in the other group
      (food only presented upon withdrawal from the stimulus) contacted the stimulus
      frequently. Withdrawal behavior from the stimulus decreased when it was no longer
      reinforced, while random presentations of the stimulus and response-independent
      food eliminated stimulus contact behavior. 

PMID- 24925657
TI  - Choice behaviour of red-winged blackbirds (Agelaius phoeniceus ) searching for
      food: The role of certain variables in stay and shift strategies.
AB  - This experiment examined the extent to which the food searching strategies of Red
      winged Blackbirds are influenced by the age of the birds and by information about
      the food supply gained from a previously visited location. Birds entered a maze
      and were given a choice between the three parallel, foraging locations. After
      making its choice, each bird was either allowed to consume all of the food
      present at the site (depletion condition) or only some of it (non-depletion
      condition). All birds were tested under both conditions. After its first choice,
      each bird was subsequently re-tested to determine if it returned to the
      previously visited site or whether it chose an alternate site. Subjects were more
      likely to choose an alternate location after experiencing the depletion
      condition. Under the non-depletion condition, adult birds showed a strong
      predisposition to return to the initially chosen sites while immature birds only
      returned to those sites randomly. The results were related to the current theory
      of staying/shifting dichotomy. 

PMID- 24925658
TI  - Effects of systemically and intrastriatally injected haloperidol and apomorphine
      on grooming, feeding and locomotion in the rat.
AB  - The effects of haloperidol and apomorphine on unconditioned behaviour of rats
      were tested in an open field. Systemically injected, the dopamine-antagonist
      haloperidol (0.01-0.3 mg/kg i.p.) decreased feeding and locomotion, but the
      average bout-length of grooming was increased at higher doses. Intrastriatally
      injected haloperidol (2.5 MUg/0.5 MUl) markedly increased grooming and to a
      lesser extent feeding. Locomotion remained unaffected. Thus, the sedative effects
      of peripherally administered haloperidol on locomotion and feeding are not
      mediated by dopamine in the antero-dorsal striatum. It is suggested that under
      haloperidol the behaviour of the animals is preferentially guided by
      exteroceptive stimuli, e.g. they show feeding and grooming while spontaneous
      behaviours which under control conditions may compete with feeding and grooming
      are suppressed. The dopamine-agonist apomorphine (0.05-2.0 mg/kg s.c.),
      systemically injected, suppressed grooming, feeding and locomotion.
      Intrastriatally injected apomorphine (5 MUg/0.5 MUl) only inhibited grooming.
      Thus, the inhibitory effects of peripherally administered apomorphine on feeding
      and locomotion are not mediated by dopamine at this site of the striatum. The
      inhibition of grooming is opposite to the effect of haloperidol and may indicate
      that dopamine in the antero-dorsal striatum is at least partly involved in a
      direct control of grooming. 

PMID- 24925659
TI  - Comparative study of the rheotaxis in the cave salamander Proteus anguinus and
      his epigean relative Necturus maculosus (Proteidae, Urodela).
AB  - The reaction to different water currents of the cave salamander Proteus anguinus
      and his epigean relative Necturus maculosus has been tested in a choice chamber.
      Both species showed a positive reaction which started in P. anguinus with a
      current of 35 cm/min and in N. maculosus 60 cm/min. These thresholds are within
      the range measured for different species of fish in the absence of visual
      stimuli. In addition, the rheotactic behaviour is less steady in N. maculosus .
      It seems that the differences found are not sufficient to be explained by
      adaptation to cave life. 

PMID- 24925660
TI  - Rate of responding as a function of ratio requirement when to supplemental
      feedings are given.
AB  - Pigeons pecked keys or pressed treadles on variable ratio schedules in which they
      earned their total daily ration of food. Ratio requirements varied in five steps
      from 15 to 240 responses per reinforcer. Results were generally similar for
      pecking and pressing. Rates of responding increased with increases in the ratio
      requirement, but decreased with increases in the obtained rates of reinforcement.
      The amount of food obtained per session also decreased with increases in the
      ratio requirement. These results are generally consistent with Hursh's behavioral
      economics model and with Allison's conservation theory. They are not consistent
      with theories, such as Herrnstein's, which predict that rates of responding will
      vary as a direct function of rates of reinforcement. 

PMID- 24925661
TI  - Preference for less segmented over more segmented reinforcement schedules:
      Stimulus and response factors.
AB  - A concurrent-chain procedure was employed to examine choice between a pair of
      differentially segmented schedules of reinforcement of equal interreinforcement
      interval ( 15 s). To assess the effect of response segmentation on choice, two
      conditions had schedules of same stimulus conditions but of different response
      conditions. The effect of stimulus segmentation was also evaluated in two other
      conditions by comparing schedules of same response conditions but of different
      stimulus conditions. With one exception, a schedule segmented by less events was
      always preferred to one that was segmented by more events. It was suggested that,
      in addition to the stimulus change, the response requirement in a segmented
      chained schedule may have also contributed to the preference shift from that
      schedule. 

PMID- 24925662
TI  - Differential Reinforcement of Response Duration (DRRD) in weanling rats: A
      comparison with adult subjects.
AB  - Weanling (21-day) and adult (3-month-old) albino rats were reinforced for lever
      press durations of 0.5, 1.0, 1.5, 2.0 and 2.5 seconds. Six sessions were
      performed at DRRD 0.5 seconds, 12 at the other values, at a pace of 3 (at DRRD
      0.5 seconds) or 6 sessions a day. Adult rats emit lower response rates, higher
      median response durations and earn more reinforcements than weanling subjects.
      The effect of age on the coefficient of variation of the response duration
      distribution is not significant, but this measure is, on average, higher for the
      weanling rats. Age-related differences are discussed in relationship to general
      activity, food motivation, schedule control and timing mechanisms. Methodological
      variables and the relationship of these results to the laws of temporal
      differentiation are also evaluated. 

PMID- 24925663
TI  - Observations on creche behaviour in suckler calves.
AB  - The creche behaviour of 16 Charolais-sired Hereford x Friesian calves and 12
      Hereford-sired Friesian x Hereford calves was studied in a hill pasture over a 4
      month period from June to September when the calves were 3-6 months old. Before
      being put onto the hill pasture in early May the calves had been penned indoors,
      from birth with their dams, in two groups. The number of hours of observation in
      each month varied from 30-36. Scan sampling and focal animal sampling were
      carried out. From the observations it was concluded that a creche was a group of
      calves each of which was lying within 20 m of its nearest neighbour. The distance
      between nearest neighbours was found to change with age. Big creches tended to be
      formed in the early morning while creches formed later in the day tended to be
      smaller in size except in the case of 5 and 6 month-old calves. The calves did
      not appear to choose any special place for lying except in bad weather. Analysis
      showed that calves tended to lie with calves from the same original group and
      that there was a preference to lie with calves of their own cross. Females were
      more sociable than males and calves with a Charolais sire were more sociable than
      those with a Hereford sire. 

PMID- 24925669
TI  - Electronic structure of Zr-Ni-Sn systems: role of clustering and nanostructures
      in half-Heusler and Heusler limits.
AB  - Half-Heusler and Heusler compounds have been of great interest for several
      decades for thermoelectric, magnetic, half-metallic and many other interesting
      properties. Among these systems, Zr-Ni-Sn compounds are interesting
      thermoelectrics which can go from semiconducting half-Heusler (HH) limit, ZrNiSn,
      to metallic Heusler (FH) limit, ZrNi2Sn. Recently Makongo et al (2011 J. Am.
      Chem. Soc. 133 18843) found that dramatic improvement in the thermoelectric power
      factor of HH can be achieved by putting excess Ni into the system. This was
      attributed to an energy filtering mechanism due to the presence of FH
      nanostructures in the HH matrix. Using density functional theory we have
      investigated clustering and nanostructure formation in ZrNi1+xSn (0 ? x ? 1)
      systems near the HH (x = 0) and FH (x = 1) ends and have found that excess Ni
      atoms in HH tend to stay close to each other and form nanoclusters. On the other
      hand, there is competing interaction between Ni-vacancies occupying different
      sites in FH which prevents them from forming vacancy nanoclusters. Effects of
      nano-inclusions on the electronic structure near HH and FH ends are discussed. 

PMID- 24925671
TI  - Comparison of four different categories of prosthetic feet during ramp ambulation
      in unilateral transtibial amputees.
AB  - BACKGROUND: Comparative effectiveness of prosthetic feet during ramp ambulation
      in unilateral transtibial amputees, who function at different Medicare Functional
      Classification Levels, has not been published. OBJECTIVE: To determine
      differences in symmetry in external work between four categories of prosthetic
      feet in K-Level-2 and K-Level-3 unilateral transtibial amputees during ramp
      ascent and descent. STUDY DESIGN: Randomized repeated-measures trial. METHODS:
      Ten subjects completed six testing sessions during which symmetry in external
      work was calculated using F-scan in-sole sensors. Between testing sessions 1 and
      2, subjects received standardized functional prosthetic training. In Sessions 3
      6, subjects tested four feet--solid ankle cushion heel, stationary attachment
      flexible endoskeleton, Talux (categories K1, K2, and K3, respectively), and
      Proprio-Foot (microprocessor ankle)--using a study socket and had a 10- to 14-day
      accommodation period with each foot. RESULTS: During ramp descent, K-Level-2
      subjects demonstrated higher symmetry in external work values with Talux and
      Proprio-Foot compared to the solid ankle cushion heel foot. K-Level-3 subjects
      also had higher symmetry in external work values with the Talux foot than the
      solid ankle cushion heel foot. Ramp ascent symmetry in external work values were
      not significantly different between feet. CONCLUSIONS: Prosthetic foot category
      appears to influence symmetry in external work more during decline walking than
      incline walking. K-Level-2 unilateral transtibial amputees achieve greater
      symmetry from K3 dynamic response prosthetic feet with J-shaped ankle and
      microprocessor ankles while descending ramps. CLINICAL RELEVANCE: The findings
      suggest that K-Level-2 unilateral transtibial amputees benefit from K3 dynamic
      response prosthetic feet with J-shaped ankle. These results support the
      prescription of K3 feet for K-Level-2 amputees who frequently negotiate ramps.

PMID- 24925672
TI  - Effect of post-trochanteric groove support on stance control associated with the
      pelvic-lumbar system: A preliminary study.
AB  - BACKGROUND: Many stroke and neuromuscular patients with paraplegia or severe
      hemiparesis cannot control trunk balance. OBJECTIVE: To support the pelvis/hip of
      paresis patients, a new pelvic/hip support system was developed bearing a convex
      pressing member placed over the post-trochanteric groove, a cutaneous landmark
      sited on the lateral portion of the gluteus maximus muscle and indicating the
      posterior aspect of the greater trochanter. STUDY DESIGN: Preliminary study.
      METHODS: Stance control differences in two paretic patients (Guillain-Barre
      syndrome and stroke sequelae) with or without post-trochanteric groove support
      were examined. The contact pressure on the post-trochanteric groove was examined
      in eight healthy volunteers using an impact force sensor. The pelvic-lumbar
      movement was also examined using three-dimensional motion analysis, and the
      gluteus muscles activity was evaluated using surface electromyography. RESULTS:
      Without post-trochanteric groove support, total three-dimensional displacement of
      the sacral marker was longer in the paresis patients than in normal controls,
      while post-trochanteric groove support decreased this distance. Post-trochanteric
      groove support provided compression pressure on the post-trochanteric groove, and
      all subjects showed a more upright trunk position, providing more anterior pelvic
      tilting. Six of eight subjects showed increased lumbar lordosis. Five of eight
      subjects showed gluteus maximus and/or gluteus medius muscle activation.
      CONCLUSION: The mechanisms of post-trochanteric groove support were suggested to
      be spino-pelvic coordination and gluteal muscle activation. CLINICAL RELEVANCE:
      The post-trochanteric groove is a cutaneous landmark located behind the
      pelvis/hip joint. Applying pressure to the post-trochanteric groove from behind
      pushes the trunk to adopt a more upright position, leading to improved stance
      control. Underlining mechanisms appear to be spino-pelvic coordination and
      gluteal muscle activation.

PMID- 24925673
TI  - Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive
      prostate cancer.
AB  - BACKGROUND: The androgen receptor (AR) is an essential gene in prostate cancer
      pathogenesis and progression. Genetic variation in AR exists, including a
      polymorphic CAG repeat sequence that is inversely associated with transcriptional
      activity. Experimental data suggest that heightened AR activity facilitates
      formation of TMPRSS2:ERG, a gene fusion present in approximately 50% of tumors of
      patients with prostate cancer. METHODS: We undertook a nested case-control study
      to investigate the hypothesis that shorter CAG repeat length would be associated
      with prostate cancer risk defined by TMPRSS2:ERG status. The study included 291
      men with prostate cancer (147 ERG-positive) and 1,221 cancer-free controls. ORs
      and 95% confidence intervals (CI) were calculated using logistic regression.
      RESULTS: Median CAG repeat length (interquartile range) among controls was 22 (20
      24). Men with shorter CAG repeats had an increased risk of ERG-positive (OR, 1.07
      per 1 repeat decrease; 95% CI, 1.00-1.14), but not ERG-negative prostate cancer
      (OR, 0.99 per 1 repeat decrease; 95% CI, 0.93-1.05). CONCLUSIONS: These data
      suggest that shorter CAG repeats are specifically associated with development of
      TMPRSS2:ERG-positive prostate cancer. IMPACT: Our results provide supportive
      evidence that androgen signaling underlies the development of prostate tumors
      that harbor TMPRSS2:ERG. Moreover, these results suggest that TMPRSS2:ERG may
      represent a unique molecular subtype of prostate cancer with an etiology distinct
      from TMPRSS2:ERG-negative disease.

PMID- 24925674
TI  - Validation of plasma proneurotensin as a novel biomarker for the prediction of
      incident breast cancer.
AB  - BACKGROUND: High fasting plasma proneurotensin concentration was associated with
      the development of breast cancer in the Malmo Diet and Cancer Study (MDCS). Here,
      we aimed at replicating the initial finding in an independent second cohort.
      METHODS: The Malmo Preventive Project (MPP) is a population study and comprised
      18,240 subjects when examined in 2002-2006. Of women without history of breast
      cancer at examination, we included all who developed breast cancer during follow
      up (n = 130) until December 31, 2010, and a random sample of women without breast
      cancer until the end of follow-up (n = 1,439) for baseline plasma proneurotensin
      assessment (mean age, 70.0 +/- 4.4 years). Proneurotensin was measured in fasting
      plasma samples and was related to the risk of later breast cancer development
      using multivariate logistic regression. RESULTS: Proneurotensin [odds ratio (OR)
      per standard deviation (SD) increment of LN-transformed proneurotensin] was
      significantly related to incident breast cancer [OR, 2.09; 95% confidence
      interval (CI), 1.79-2.44; P < 0.001; adjusted for age, body mass index (BMI),
      smoking, and hormone replacement therapy]. The effect estimate in the MPP was
      larger than in the discovery cohort (MDCS), with the main difference between the
      two cohorts being that women of the MPP study were on the average about 10 years
      older and follow-up time was shorter than that of the MDCS. CONCLUSION: As
      initially found in the MDCS, fasting plasma proneurotensin was significantly
      associated with the development of breast cancer in the MPP study as well.
      IMPACT: Measurement of plasma proneurotensin warrants further investigation as a
      blood-based marker for early breast cancer detection.

PMID- 24925675
TI  - Make your own cigarettes: toxicant exposure, smoking topography, and subjective
      effects.
AB  - BACKGROUND: Despite considerable use of make your own (MYO) cigarettes worldwide
      and increasing use in the United States, relatively little is known about how
      these cigarettes are smoked and the resultant toxicant exposure. METHODS: In a
      laboratory study, we compared two types of MYO cigarettes-roll your own (RYO) and
      personal machine made (PMM)-with factory-made (FM) cigarettes in three groups of
      smokers who exclusively used RYO (n = 34), PMM (n = 23), or FM (n = 20). Within
      each group, cigarettes were smoked in three conditions: (i) after confirmed
      overnight tobacco abstinence; (ii) in an intense smoking paradigm; and (iii)
      without restrictions. All cigarettes were smoked ad lib through a smoking
      topography unit. RESULTS: Plasma nicotine significantly increased after
      cigarettes in all conditions except PMM in the intense smoking paradigm. Puff
      volume, puff duration, total puff volume, and puff velocity did not differ
      between cigarette types but the puffs per cigarette and time to smoke were
      significantly smaller for RYO compared with PMM and FM. Regardless of the
      cigarette, participants consumed the first three puffs more vigorously than the
      last three puffs. CONCLUSIONS: Despite the belief of many of their consumers,
      smoking MYO cigarettes is not a safe alternative to FM cigarettes. Like FM, MYO
      cigarettes expose their users to harmful constituents of tobacco smoke. Despite
      differences in size and design their puffing profiles are remarkably similar.
      IMPACT: These data are relevant to health and regulatory considerations on the
      MYO cigarettes.

PMID- 24925676
TI  - Risk of hospitalization for survivors of childhood and adolescent cancer.
AB  - BACKGROUND: Childhood cancer survivors may be at increased risk of
      hospitalization because of cancer-related late effects. METHODS: Using data from
      population-based research resources in Utah, we identified childhood and
      adolescent cancer survivors who were diagnosed from 1973 to 2005 (N = 2,571). We
      selected a comparison cohort based on birth year and sex (N = 7,713).
      Hospitalizations from 1996 to 2010, excluding pregnancy and delivery, were
      determined from discharge records. Multivariable regressions were used to
      evaluate hospitalization admissions, length of stay, and diagnosis for survivors
      starting five years from diagnosis versus the comparison cohort. RESULTS: When
      follow-up began in 1996, there were N = 1,499 survivors and N = 7,219 comparisons
      who were alive and eligible for follow-up. Average follow-up for survivors was
      13.5 years (SD = 8.5) and for the comparison 14.0 years (SD = 8.7; P = 0.05).
      Survivors were hospitalized, on average, 1.62 (SD = 3.37) times contrasted to
      0.79 (SD = 1.73) for the comparison cohort. In multivariable analyses, the hazard
      ratio (HR) of any hospitalization since 1996 was higher for survivors than the
      comparison cohort [HR, 1.52, 95% confidence interval (CI), 1.31-1.66]. Survivors
      experienced a higher hospital admission rate [rate ratio (RR) = 1.67; 95% CI,
      1.58-1.77] than the comparison cohort. The number of hospitalizations was highest
      for neuroblastoma (RR = 2.21; 95% CI, 1.84-2.66) and bone tumors (RR = 2.55; 95%
      CI, 2.14-3.02) in reference to the comparison cohort. Survivors were hospitalized
      because of blood disorders more often (HR, 14.2; 95% CI, 6.3-32.0). CONCLUSIONS:
      The risk of hospitalization and lengths of stay are elevated among childhood
      cancer survivors. IMPACT: Research to identify strategies to prevent and manage
      survivors' health problems in outpatient settings is needed.

PMID- 24925677
TI  - Teriflunomide (Aubagio(r)) for the treatment of multiple sclerosis.
AB  - Teriflunomide (Aubagio(r)) is a once-daily oral immunomodulatory disease
      modifying therapy (DMT) presently approved in several regions, including Europe,
      North America, Latin America and Australia, for the treatment of relapsing forms
      of multiple sclerosis (RMS; RRMS). The therapeutic mode of action of
      teriflunomide in MS continues to be investigated. This review summarizes the main
      efficacy and safety results of the clinical trial program leading to
      teriflunomide's approval, highlights a number of practical clinical
      considerations, and overviews its presumed therapeutic mode of action (MOA) based
      on pharmacokinetic and pharmacodynamic observations and the growing body of
      teriflunomide-related in vitro, pre-clinical (animal model), and in vivo human
      studies. 

PMID- 24925678
TI  - Axonal dysfunction with voltage gated potassium channel complex antibodies.
AB  - OBJECTIVE: Although autoantibodies targeted against voltage-gated potassium
      channel (VGKC)-associated proteins have been identified in limbic encephalitis
      (LE) and acquired neuromyotonia (aNMT), the role of these antibodies in disease
      pathophysiology has not been elucidated. The present study investigated axonal
      function across the spectrum of VGKC-complex antibody associated disorders.
      METHODS: Peripheral axonal excitability studies were undertaken in a cohort of
      patients with LE (N=6) and aNMT (N=11), compared to healthy controls (HC; N=20).
      RESULTS: Patients with LE demonstrated prominent abnormalities in peripheral
      axonal excitability during the acute phase, with reduced threshold change in
      threshold electrotonus (depolarizing 10-20 LE: 58.5+/-3.1%; HC: 67.4+/-0.9%;
      P<.005; S2 accommodation LE: 17.2+/-1.4%; HC: 22.2+/-0.6%; P<=.005) and in
      recovery cycle parameters (superexcitability LE: -16.0+/-0.9%; HC: -23.4+/-1.1%;
      P<.01; subexcitability LE: 8.5+/-1.2%; HC: 13.8+/-0.7%; P<=.005). The pattern of
      change in LE patients was dissimilar to the effects of antiepileptic medications,
      suggesting that these factors did not underlie excitability changes in LE.
      Normalization of excitability parameters was associated with recovery (TEd peak
      correlation coefficient=.868; P=.002), suggesting that peripheral excitability
      studies may provide a marker associated with clinical improvement. In contrast,
      patients with aNMT demonstrated no significant changes at the site of
      stimulation. CONCLUSIONS: The lack of prominent excitability abnormalities in
      patients with aNMT likely reflects a distal origin of hyperexcitability, expected
      to be at the motor nerve terminal, while the prominent changes observed in
      patients with LE likely represent a complex disturbance at the level of the
      axonal membrane, combined with electrolyte imbalance and adaptive change.

PMID- 24925679
TI  - Potato Production, Usage, and Nutrition--A Review.
AB  - Potato is an economically important staple crop prevailing all across the world
      with successful large-scale production, consumption, and affordability with easy
      availability in the open market. Potatoes provide basic nutrients such as
      carbohydrates, dietary fiber (skin), several vitamins, and minerals (e.g.,
      potassium, magnesium, iron). On occasion exposures to raw and cooked potatoes
      impart allergic reactions. Dietary intake of potatoes, especially colored
      potatoes, play an important role in the production of antioxidant defense system
      by providing essential nutrient antioxidants, such as vitamins, beta-carotene,
      polyphenols, and minerals. This may help lower the incidence of wide range of
      chronic and acute disease processes (like hypertension, heart diseases, cancer,
      neurodegenerative, and other diseases). However, retention of nutrients in
      potatoes is affected by various cooking and processing methods. Cooking at
      elevated temperature also produces acrylamide-a suspected carcinogen. Independent
      and/or collaborative studies have been conducted and reported on the various
      pathways leading to the formation of acrylamide in heat processed foods. This
      article reviews the latest research on potato production, consumption, nature of
      phytochemicals and their health benefits, and allergic reactions to children.
      Also included is the discovery of acrylamide in processed starch-rich foods
      including potatoes, mechanism of formation, detection methodologies, and
      mitigation steps to reduce acrylamide content in food. 

PMID- 24925680
TI  - Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired
      end reads.
AB  - BACKGROUND: Adapter trimming is a prerequisite step for analyzing next-generation
      sequencing (NGS) data when the reads are longer than the target DNA/RNA
      fragments. Although typically used in small RNA sequencing, adapter trimming is
      also used widely in other applications, such as genome DNA sequencing and
      transcriptome RNA/cDNA sequencing, where fragments shorter than a read are
      sometimes obtained because of the limitations of NGS protocols. For the newly
      emerged Nextera long mate-pair (LMP) protocol, junction adapters are located in
      the middle of all properly constructed fragments; hence, adapter trimming is
      essential to gain the correct paired reads. However, our investigations have
      shown that few adapter trimming tools meet both efficiency and accuracy
      requirements simultaneously. The performances of these tools can be even worse
      for paired-end and/or mate-pair sequencing. RESULTS: To improve the efficiency of
      adapter trimming, we devised a novel algorithm, the bit-masked k-difference
      matching algorithm, which has O(kn) expected time with O(m) space, where k is the
      maximum number of differences allowed, n is the read length, and m is the adapter
      length. This algorithm makes it possible to fully enumerate all candidates that
      meet a specified threshold, e.g. error ratio, within a short period of time. To
      improve the accuracy of this algorithm, we designed a simple and easy-to-explain
      statistical scoring scheme to evaluate candidates in the pattern matching step.
      We also devised scoring schemes to fully exploit the paired-end/mate-pair
      information when it is applicable. All these features have been implemented in an
      industry-standard tool named Skewer (https://sourceforge.net/projects/skewer).
      Experiments on simulated data, real data of small RNA sequencing, paired-end RNA
      sequencing, and Nextera LMP sequencing showed that Skewer outperforms all other
      similar tools that have the same utility. Further, Skewer is considerably faster
      than other tools that have comparative accuracies; namely, one times faster for
      single-end sequencing, more than 12 times faster for paired-end sequencing, and
      49% faster for LMP sequencing. CONCLUSIONS: Skewer achieved as yet unmatched
      accuracies for adapter trimming with low time bound.

PMID- 24925681
TI  - In response to Redefining successful therapy in obstructive sleep apnea: a call
      to arms.

PMID- 24925682
TI  - Chemical space networks: a powerful new paradigm for the description of chemical
      space.
AB  - The concept of chemical space is playing an increasingly important role in many
      areas of chemical research, especially medicinal chemistry and chemical biology.
      It is generally conceived as consisting of numerous compound clusters of varying
      sizes scattered throughout the space in much the same way as galaxies of stars
      inhabit our universe. A number of issues associated with this coordinate-based
      representation are discussed. Not the least of which is the continuous nature of
      the space, a feature not entirely compatible with the inherently discrete nature
      of chemical space. Cell-based representations, which are derived from coordinate
      based spaces, have also been developed that facilitate a number of chemical
      informatic activities (e.g., diverse subset selection, filling 'diversity voids',
      and comparing compound collections).These representations generally suffer the
      'curse of dimensionality'. In this work, networks are proposed as an attractive
      paradigm for representing chemical space since they circumvent many of the issues
      associated with coordinate- and cell-based representations, including the curse
      of dimensionality. In addition, their relational structure is entirely compatible
      with the intrinsic nature of chemical space. A description of the features of
      these chemical space networks is presented that emphasizes their statistical
      characteristics and indicates how they are related to various types of network
      topologies that exhibit random, scale-free, and/or 'small world' properties. 

PMID- 24925683
TI  - Electrochemical synthesis of sulfonamide derivatives based on the oxidation of
      2,5-diethoxy-4-morpholinoaniline in the presence of arylsulfinic acids.
AB  - Some new sulfonamide derivatives were synthesized in aqueous solutions via anodic
      oxidation of 2,5-diethoxy-4-morpholinoaniline in the presence of arylsulfinic
      acids using a commercial carbon anode. In addition, the formation mechanism of
      the products was discussed. The obtained data show that the electrogenerated
      quinone diimine undergoes a Michael-type addition reaction with arylsulfinic
      acids to yield the respective sulfonamide derivatives. In this work, two
      different types of products (mono- and disulfone derivatives) in the same
      precursor could be isolated just by controlling the exerted potentials. 

PMID- 24925684
TI  - Determination of melanin types and relative concentrations: an observational
      study using a non-invasive inverse skin reflectance analysis.
AB  - OBJECTIVE: Melanin is a major skin colour pigment that is made up of eumelanin
      (the dark brown-black colour) and pheomelanin (the light red-yellow colour)
      pigments. Skin-whitening products typically contain depigmentation agents that
      reduce the level of pigmentation by changing the pheomelanin-eumelanin
      production. Similarly, in skin pigment treatment of skin disorders, the melanin
      production is managed accordingly. To assess and improve treatment efficacy, it
      is important to have a measurement tool that is capable of determining the
      melanin types objectively. So far, the efficacy assessment is subjective. In this
      study, an inverse skin reflectance pigmentation analysis system that determines
      eumelanin and pheomelanin content is developed and evaluated in an observational
      study involving 36 participants with skin photo type IV. METHODS: The reflectance
      spectra of the left forearms of participants were analysed by the pigmentation
      analysis system to determine their skin parameters--pheomelanin and eumelanin
      concentrations, melanosome volume fraction, and epidermal thickness. The
      determined skin parameters are then inputted into the realistic skin model (RSM)
      of the Advanced Systems Analyses Program (asap(r)) to generate the ground truth
      reflectance spectra for the given skin parameters to validate the system.
      RESULTS: The developed pigmentation analysis system is found to be accurate with
      a spectral error of 0.0163 +/- 0.009 between measured reflectance and the
      reflectance output of the analysis system and RSM. The regression analysis shows
      a strong linear relationship (R(2) = 0.994) indicating good precision. The
      relative concentrations of pheomelanin (38.23 +/- 15.04) and eumelanin (1.68 +/-
      0.91) analysed by the system gives a ratio of pheomelanin to eumelanin of 0.048
      +/- 0.029; this value is consistent with previously reported figure of 0.049.
      CONCLUSION: The proposed pigmentation analysis system is able to determine
      melanin types and their relative concentrations. It has the potential to assess
      the efficacy of the skin-whitening and pigmentation treatments objectively in a
      non-invasive manner.

PMID- 24925685
TI  - The eCollaborative: using a quality improvement collaborative to implement the
      National eHealth Record System in Australian primary care practices.
AB  - QUALITY PROBLEM: The new national patient-controlled electronic health record is
      an important quality improvement, and there was a pressing need to pilot its use
      in Australian primary care practices. Implementation of electronic health records
      in other countries has met with mixed success. INITIAL ASSESSMENT: New work was
      required in general practices participating in the national electronic health
      record. National implementers needed to engage with small private general
      practices to test the changes before general introduction. CHOICE OF SOLUTION:
      The National E-health Transition Authority contracted the Improvement Foundation
      Australia to conduct a quality improvement collaborative based on 9 years of
      experience with the Australian Primary Care Collaborative Program.
      IMPLEMENTATION: Aims, measures and change ideas were addressed in a collaborative
      programme of workshops and supported activity periods. Data quality measures and
      numbers of health summaries uploaded were collected monthly. Challenges such as
      the delay in implementation of the electronic health summary were met.
      EVALUATION: Fifty-six practices participated. Nine hundred and twenty-nine
      patients registered to participate, and 650 shared health summaries were
      uploaded. Five hundred and nineteen patient views occurred. Four hundred and
      twenty-one plan/do/study/act cycles were submitted by participating practices.
      LESSONS LEARNED: The collaborative methodology was adapted for implementing
      innovation and proved useful for engaging with multiple small practices,
      facilitating low-risk testing of processes, sharing ideas among participants,
      development of clinical champions and development of resources to support wider
      use. Email discussion between participants and system designers facilitated
      improvements. Data quality was a key challenge for this innovation, and quality
      measures chosen require development. Patient participants were partners in
      improvement.

PMID- 24925686
TI  - Effects of diphenyl diselenide on behavioral and biochemical changes induced by
      amphetamine in mice.
AB  - Diphenyl diselenide (PhSe)2, an organoselenium compound, has been studied as a
      potential pharmacological agent in different in vitro and in vivo models, mainly
      due to its antioxidant properties. However, there are few studies concerning the
      effects of (PhSe)2 on dopaminergic system. Thus, the purpose of the present study
      was to evaluate the effects of acute and sub-chronic treatment of (PhSe)2 on
      amphetamine-induced behavioral and biochemical parameters. In acute protocol,
      mice were pre-treated with 5 or 10 mg/kg of (PhSe)2 and 30 min after, amphetamine
      was administered. In sub-chronic protocol, mice were pre-treated with 5 or 10
      mg/kg of (PhSe)2 during 7 days and 24 h after, amphetamine was administered.
      Twenty-five minutes after amphetamine administration, behavioral (crossing,
      rearing, time of stereotypy and immobility) and biochemical (MAO activity, DCFH
      DA oxidation, protein and non-protein thiol groups) parameters were analyzed.
      Amphetamine increased the number of crossing and rearing and (PhSe)2 prevented
      only the increase in the number of crossings when acutely administered to mice.
      Furthermore, amphetamine increased stereotypy and time of immobility in mice.
      (PhSe)2, at 10 mg/kg, increased per se the stereotypy and time of immobility when
      sub-chronically administered. (PhSe)2, at 10 mg/kg, potentiated the stereotypy
      caused by amphetamine in both protocols. Sub-chronic treatment with (PhSe)2
      either alone (5 and 10 mg/kg) or in combination (10 mg/kg) with amphetamine
      decreased brain MAO-B activity. Oxidative stress parameters were not modified by
      (PhSe)2 and/or amphetamine treatments. In conclusion, sub-chronic administration
      of (PhSe)2 can promote a behavioral sensitization that seems to be, at least in
      part, dependent of MAO-B inhibition.

PMID- 24925687
TI  - Impact of adrenalectomy and dexamethasone treatment on testicular morphology and
      sperm parameters in rats: insights into the adrenal control of male reproduction.
AB  - Here we investigated the hypothesis that normal levels of glucocorticoids, a
      class of adrenal steroid hormones, are required for normal testicular and
      epididymal functions. We examined the effects of the manipulation of
      glucocorticoid plasma levels by bilateral adrenalectomy (1, 2, 7 and 15 days)
      alone or in combination with daily treatment with the synthetic glucocorticoid
      dexamethasone (DEX; 5 MUg/kg, i.p., 6 days) on the morphology of the testis and
      sperm parameters in rats. We showed that adrenalectomy led to a reduction in
      testicular sperm count and daily sperm production starting 2 days after surgery
      and a differential decrease in sperm count in the epididymis, according to the
      region and time post-adrenalectomy analysed. In parallel, testes from 7-day
      adrenalectomized (ADX) rats displayed a higher frequency of damaged seminiferous
      tubules and the presence of elongated spermatids retained in the basal epithelial
      compartment in stages IX-XVII, which is indicative of defective spermiation. The
      alkaline comet assay revealed a late effect of adrenalectomy on epididymal sperm
      DNA fragmentation, which was increased only 15 days after surgery. DEX treatment
      prevented the changes in testicular and epididymal sperm count observed in 7-day
      ADX rats, but failed to protect the testis from ADX-induced morphological
      abnormalities. Thus, our results indicated that glucocorticoids may be involved
      in events related to the maintenance of spermatogenesis and sperm maturation
      during adulthood. These findings provide new insights into the importance of
      adrenal steroids to male fertility. 

PMID- 24925688
TI  - Opposing roles for Smad2 and Smad3 in peritoneal fibrosis in vivo and in vitro.
AB  - Peritoneal fibrosis is a major cause of ultrafiltration failure in patients
      receiving continuous ambulatory peritoneal dialysis. Transforming growth factor
      (TGF)-beta1 is an important mediator in this process; however, its signaling
      mechanisms had not been explored. Thus, we examined TGF-beta1/Smad signaling in
      human peritoneal biopsy specimens associated with continuous ambulatory
      peritoneal dialysis. We found that TGF-beta/Smad2/3 signaling was highly
      activated in patients with increased collagen deposition and thickening of the
      peritoneal membrane who were receiving continuous ambulatory peritoneal dialysis.
      Long-term exposure of wild-type mice to 4.25% peritoneal dialysis solution for 30
      days induced significant peritoneal fibrosis with impaired peritoneal
      equilibrium, which was prevented in Smad3 knockout mice. In contrast, conditional
      Smad2 gene deletion in the peritoneum exacerbated peritoneal fibrosis and
      dysfunction. The contrasting roles of Smad2 and Smad3 in peritoneal fibrosis were
      also examined in vitro. Cultured mesothelial cells from Smad3 knockout mice were
      resistant to TGF-beta1-induced collagen I production and the transition toward a
      myofibroblast phenotype as seen in wild-type cells, whereas Smad2 deficiency in
      mesothelial cells failed to modulate the profibrotic response to TGF-beta1. In
      conclusion, this study found activation of TGF-beta/Smad signaling in peritoneal
      fibrosis in patients receiving continuous ambulatory peritoneal dialysis and
      identifies opposing roles for Smad2 and Smad3 in peritoneal dialysis-associated
      peritoneal fibrosis. These findings provide a mechanistic basis for future
      therapies targeting TGF-beta/Smad signaling in peritoneal fibrosis. 

PMID- 24925689
TI  - Uterine sarcoma dissemination during myomectomy: if not "acceptable collateral
      damage," is it possible to mitigate the risk?

PMID- 24925690
TI  - Evaluating reporting heterogeneity in self-rated health among adults aged 50
      years and above in India: an anchoring vignettes analytic approach.
AB  - OBJECTIVE: To use anchoring vignettes to evaluate reporting heterogeneity (RH) in
      self-rated mobility and cognition in older adults. METHOD: We analyzed vignettes
      and self-rated mobility and cognition in 2,558 individuals aged 50 years and
      above. We tested for assumptions of vignette equivalence (VE) and response
      consistency (RC). We used a joint hierarchical ordered probit (HOPIT) model to
      evaluate self-rating responses for RH. RESULTS: The assumption of VE was met
      except for "learning" vignettes. Higher socioeconomic status (SES) and education
      significantly lowered thresholds for cognition ratings. After correction for RH,
      women, lower SES, and older respondents were significantly more likely to report
      greater difficulty in mobility. The influence of age, SES, and education on
      thresholds was less apparent for cognition. DISCUSSION: Our study provides strong
      evidence of RH in self-rated mobility and cognition. We highlight the need to
      formally test basic assumptions before using vignettes to adjust self-rating
      responses for RH.

PMID- 24925691
TI  - Dental care utilization and unmet dental needs in older Korean Americans.
AB  - OBJECTIVE: The study explored predictors of dental care utilization and unmet
      dental needs in older Korean Americans, considering predisposing, enabling
      (dental insurance, acculturation, and family network), and need (self-rated oral
      health) variables. METHOD: Multivariate regression models were used to evaluate
      the data from 209 Korean Americans (aged >= 60) surveyed in Central Texas.
      RESULTS: Participants with strong family networks and fair/poor self-ratings of
      oral health reported higher numbers of dental visits in the past year. The
      likelihood of having an unmet dental need increased when participants had less
      education, a shorter stay in the United States, no dental insurance coverage,
      lower levels of acculturation, more limited family networks, fair/poor self
      ratings of oral health, and fewer numbers of dental visits. DISCUSSION: Our
      findings underscore the vulnerability of individuals who are culturally and
      linguistically isolated and lack family resources, and they highlight the
      importance of incorporating social and cultural factors in intervention efforts.

PMID- 24925694
TI  - The association between Helicobacter pylori gastritis and lymphoid aggregates,
      lymphoid follicles and intestinal metaplasia in gastric mucosa of children.
AB  - AIMS: The aim of the study was to determine the topographic prevalence of
      lymphoid follicles, lymphoid aggregates, gastric glandular atrophy and intestinal
      metaplasia among children with chronic abdominal pain. The association between
      these lesions and age, type of gastritis and Helicobacter pylori density was also
      assessed. METHODS: A total of 358 patients (mean age: 10, 18 +/- 3, 26 years;
      male : female ratio: 0.92) with chronic abdominal pain who had upper
      gastrointestinal endoscopy were included in the study. The endoscopic and
      histopathological findings were documented. The prevalence of lymphoid follicles,
      lymphoid aggregates, atrophy and intestinal metaplasia according to the type of
      gastritis and their relation with H. pylori density were determined. RESULTS: H.
      pylori was detected in 214 (59.8%) patients. H. pylori- positive patients were
      found to be significantly older than H. pylori-negative patients (P < 0.01). The
      endoscopy revealed that the most common finding observed was antral nodularity in
      H. pylori-positive patients and normal mucosal appearance in H. pylori-negative
      patients. Panmucosal gastritis both in the corpus and antrum and the prevalence
      of lymphoid follicles and lymphoid aggregates were more frequent in the H. pylori
      positive group (P < 0.01). None of the patients had atrophy, whereas 11 patients
      had intestinal metaplasia. Although positive correlation was obtained between
      lymphoid lesions and H. pylori density, no significant relation was established
      between intestinal metaplasia, lymphoid lesions and H. pylori density.
      CONCLUSION: Lymphoid follicles and lymphoid aggregates in gastric mucosa
      involving both antrum and corpus significantly correlated with H. pylori
      infection, H. pylori density and type of gastritis in children.

PMID- 24925693
TI  - Impaired response or insufficient dosage? Examining the potential causes of
      "inadequate response" to allopurinol in the treatment of gout.
AB  - OBJECTIVES: Gout is one of the most common forms of arthritis. It is well
      established that urate-lowering therapy that aims for a serum urate less than at
      least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout.
      Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate
      lowering therapy. However, many patients fail to achieve the target serum urate
      on allopurinol; these patients can be considered to have "inadequate response" to
      allopurinol. Herein, we examine the potential mechanisms and implications of
      inadequate response to allopurinol. METHODS: The literature was reviewed for
      potential causes for failure to reach target serum urate in patients receiving
      allopurinol. RESULTS: The two most common causes of inadequate response to
      allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients
      who fail to achieve target serum urate on standard doses of allopurinol form a
      group that could be considered to be "partially resistant" to allopurinol. There
      are four potential mechanisms for partial allopurinol resistance: decreased
      conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol;
      abnormality in XO structure and/or function such that oxypurinol is rendered less
      effective and/or drug interactions. CONCLUSIONS: It is important to determine the
      reasons for failure to achieve treatment targets with allopurinol, particularly
      as newer agents become available. The knowledge of the mechanisms for inadequate
      response may help guide the clinician towards making a therapeutic choice that is
      more likely to result in achieving the serum urate target.

PMID- 24925695
TI  - Eutrophication as a driver of r-selection traits in a freshwater fish.
AB  - This study tested whether eutrophication could influence life-history traits of a
      cyprinid, Chanodichthys erythropterus, in 10 Chinese lakes. Using the von
      Bertalanffy growth model, the asymptotic length (Linfinity ) and the growth
      performance index (IGRO ) were significantly affected by eutrophication. The
      gonado-somatic index (IG ) and relative fecundity (FR ) were significantly lower
      in mesotrophic lakes than in eutrophic and hypertrophic lakes. These results
      indicate that increasing eutrophication affects the life-history tactics of a
      freshwater fish. 

PMID- 24925692
TI  - Health Assessment Questionnaire disability progression in early rheumatoid
      arthritis: systematic review and analysis of two inception cohorts.
AB  - OBJECTIVE: The Health Assessment Questionnaire is widely used for patients with
      inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In
      this study, we evaluated the progression of HAQ scores in RA (i) by
      systematically reviewing the published literature on the methods used to assess
      changes in functional disability over time and (ii) to study in detail HAQ
      progression in two large prospective observational studies from the UK. METHODS:
      Data from two large inception cohorts, ERAS and NOAR, were studied to determine
      trajectories of HAQ progression over time by applying latent class growth models
      (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration,
      rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status
      (SES) were included as potential predictors of HAQ trajectory subgroup
      membership. RESULTS: The literature search identified 49 studies showing that HAQ
      progression has mainly been based on average changes in the total study
      population. In the HAQ progression study, a LCGM with four HAQ trajectory
      subgroups was selected as providing the best fit in both cohorts. In both the
      cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987
      ACR criteria, higher DAS28 and lower SES were associated with increased
      likelihood of membership of subgroups with worse HAQ progression. CONCLUSION:
      Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR
      cohorts. The fact that the subgroups identified were nearly identical supports
      their validity. Identifying distinct groups of patients who are at risk of poor
      functional outcome may help to target therapy to those who are most likely to
      benefit.

PMID- 24925696
TI  - Whole-cell double oxidation of n-heptane.
AB  - Biocascades allow one-pot synthesis of chemical building blocks omitting
      purification of reaction intermediates and expenses for downstream processing.
      Here we show the first whole cell double oxidation of n-heptane to produce chiral
      alcohols and heptanones. The concept of an artificial operon for co-expression of
      a monooxygenase from Bacillus megaterium (P450 BM3) and an alcohol dehydrogenase
      (RE-ADH) from Rhodococcus erythropolis is reported and compared to the widely
      used two-plasmid or Duet-vector expression systems. Both catalysts are co
      expressed on a polycistronic constructs (single mRNA) that reduces recombinant
      DNA content and metabolic burden for the host cell, therefore increasing growth
      rate and expression level. Using the artificial operon system, the expression of
      P450 BM3 reached 81mgg(-1) cell dry weight. In addition, in situ cofactor
      regeneration through the P450 BM3/RE-ADH couple was enhanced by coupling to
      glucose oxidation by E. coli. Under optimized reaction conditions the artificial
      operon system displayed a product formation of 656mgL(-1) (5.7mM) of reaction
      products (heptanols+heptanones), which is 3-fold higher than the previously
      reported values for an in vitro oxidation cascade. In conjunction with the high
      product concentrations it was possible to obtain ee values of >99% for (S)-3
      heptanol. Coexpression of a third alcohol dehydrogenase from Lactobacillus brevis
      (Lb-ADH) in the same host yielded complete oxidation of all heptanol isomers.
      Introduction of a second ADH enabled further to utilize both cofactors in the
      host cell (NADH and NADPH) which illustrates the simplicity and modular character
      of the whole cell oxidation concept employing an artificial operon system. 

PMID- 24925697
TI  - Functional limitations due to fatigue among independently ambulant stroke
      survivors in Osun, South-Western Nigeria.
AB  - BACKGROUND AND PURPOSE: Functional limitations in stroke survivors are sometimes
      associated with fatigue. This study assessed the functional limitations due to
      fatigue in community-dwelling stroke survivors undergoing physiotherapy. The
      differences in functional limitations due to fatigue were determined between
      sexes, stroke types, sides of affectation, age categories and levels of
      disability. Relationships between functional limitation due to fatigue and these
      variables were also determined. METHODS: This was a cross-sectional study
      involving 63 stroke survivors (35 male survivors and 28 female survivors) with
      ages ranging from 45 to 79 years (mean = 53.68 +/- 10.95 years). Functional
      limitation due to fatigue was assessed with the modified fatigue impact scale
      (MFIS). Modified Rankin scale was used to categorize the disability of the
      participants. Data were analysed using descriptive (mean, standard deviation,
      percentage and frequency) and inferential (Mann-Whitney U-test and Spearman
      correlation analysis) statistics. Significance was set at 0.05 alpha level.
      RESULTS/FINDINGS: The mean MFIS score was 31.74 +/- 12.39. Many participants
      (58.7%) had moderate functional limitations due to fatigue. The result of Mann
      Whitney U-test showed significant difference in functional limitation due to
      fatigue between participants with slight disability and those with moderate
      disability (p = 0.000), with participants with moderate disability having higher
      MFIS scores (more functional limitations). There was also a significant
      correlation between functional limitation due to fatigue and level of disability
      (rho = 0.625, p = 0.000). DISCUSSION: Functional limitation due to fatigue occurs
      frequently in stroke survivors and is related to level of disability. Functional
      limitations due to fatigue should be assessed frequently in all stroke survivors
      with varying degrees of disability and the outcome should be considered during
      rehabilitation and retraining of physical function.

PMID- 24925698
TI  - On the impact of physiological noise in spinal cord functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) techniques are widely exploited for
      the study of brain activation. In recent years, similar approaches have been
      attempted for the study of spinal cord function; however, obtaining good
      functional images of spinal cord still represents a technical and scientific
      challenge. Some of the main limiting factors can be classified under the broad
      category of "physiological noise," and are related to 1) the cerebrospinal fluid
      (CSF) flux in the subarachnoid space surrounding the spinal cord; 2) the cord
      motion itself; and 3) the small area of the cord, which makes it critical to have
      a high image resolution. In addition, the different magnetic susceptibility
      properties of tissues surrounding the spinal cord reduce the local homogeneity of
      the static magnetic field, causing image distortion, reduction of the effective
      resolution, and signal loss, all effects that are modulated by motion. For these
      reasons, a number of methods have been developed for the purpose of denoising
      spinal cord fMRI time series. In this work, after a short introduction on the
      relevant features of the spinal cord anatomy, we review the main sources of
      physiological noise in spinal cord fMRI and discuss the main approaches useful
      for its mitigation.

PMID- 24925699
TI  - Validation of an innovative method of shoulder range-of-motion measurement using
      a smartphone clinometer application.
AB  - BACKGROUND: An accurate and reliable measurement of shoulder range of motion
      (ROM) is important in the evaluation of the shoulder. A smartphone digital
      clinometer application is a potentially simpler method for measuring shoulder
      ROM. The goal of this study was to establish the reliability and validity of
      shoulder ROM measurements among varying health care providers using a smartphone
      clinometer application in healthy and symptomatic adults. METHODS: An attending
      surgeon, fellow, resident, physician assistant, and student served as examiners.
      Bilateral shoulders of 24 healthy subjects were included. Fifteen postoperative
      patients served as the symptomatic cohort. Examiners measured ROM of each
      shoulder, first using visual estimation and then using a goniometer and
      smartphone clinometer in a randomized fashion. RESULTS: The interobserver
      reliability among examiners showed significant correlation, with average
      intraclass correlation coefficient [ICC(2,1)] values of 0.61 (estimation), 0.69
      (goniometer), and 0.80 (smartphone). All 5 examiners had substantial agreement
      with the gold standard in healthy subjects, with average ICC(2,1) values ranging
      from 0.62 to 0.79. The interobserver reliability in symptomatic patients showed
      significant correlation, with average ICC(2,1) values of 0.72 (estimation), 0.79
      (goniometer), and 0.89 (smartphone). Examiners had excellent agreement with the
      gold standard in symptomatic patients, with an average ICC(2,1) value of 0.98.
      CONCLUSION: The smartphone clinometer has excellent agreement with a goniometer
      based gold standard for measurement of shoulder ROM in both healthy and
      symptomatic subjects. There is good correlation among different skill levels of
      providers for measurements obtained using the smartphone. A smartphone-based
      clinometer is a good resource for shoulder ROM measurement in both healthy
      subjects and symptomatic patients.

PMID- 24925700
TI  - Does the timing of surgery for proximal humeral fracture affect inpatient
      outcomes?
AB  - BACKGROUND: Delayed surgical treatment of hip fractures is associated with
      adverse medical outcomes, but it is unclear whether the same is true for proximal
      humeral fractures. The purpose of this study was to evaluate the relationship
      between surgical delay for proximal humeral fracture and inpatient adverse
      events, in-hospital death, prolonged postoperative stay, and nonroutine
      discharge. METHODS: Of the more than 70,000 patients with an operatively treated
      proximal humeral fracture identified in the Nationwide Inpatient Sample between
      2008 and 2011, 87% underwent surgery within 2 days of admission and 13% underwent
      surgery 3 days or more after admission. Multivariable logistic regression
      analyses were performed to evaluate the effect of surgical delay on inpatient
      outcomes and to identify risk factors associated with late surgery. RESULTS:
      Surgery 3 days or more after admission for fracture of the proximal humerus had
      no influence on in-hospital death but was independently associated with inpatient
      adverse events (odds ratio [OR], 2.1; 95% confidence interval [CI], 2.0-2.2),
      prolonged postoperative stay (OR, 1.7; 95% CI, 1.7-1.9), and increased nonroutine
      discharge (OR, 2.7; 95% CI, 2.6-2.9). Risk factors for surgery 3 days or more
      after admission included advanced age, male sex, Elixhauser comorbidity score,
      polytrauma, Hispanic race or black race, no insurance coverage, low household
      income, and weekend admission. CONCLUSIONS: Even when comorbidities and
      complexity are controlled for, delaying surgery for proximal humeral fracture is
      likely to increase inpatient morbidity, postoperative length of stay, and
      nonroutine discharge. It appears that avoiding nonmedical delays is advantageous.

PMID- 24925701
TI  - Biomechanical analysis of the modified Bristow procedure for anterior shoulder
      instability: is the bone block necessary?
AB  - BACKGROUND: Anterior shoulder instability with bone loss can be treated
      successfully with the modified Bristow procedure. Opinions vary regarding the
      role of the soft-tissue sling created by the conjoined tendon after transfer.
      Therefore, the aim of this study was to determine the effect of the modified
      Bristow procedure and conjoined tendon transfer on glenohumeral translation and
      kinematics after creating anterior instability. METHODS: Eight cadaveric
      shoulders were tested with a custom shoulder testing system. Range-of-motion,
      translation, and kinematic testing was performed in 60 degrees  of glenohumeral
      abduction in the scapular and coronal planes under the following conditions:
      intact joint, Bankart lesion with 20% glenoid bone loss, modified Bristow
      procedure, and soft tissue-only conjoined tendon transfer. RESULTS: A Bankart
      lesion with 20% bone loss resulted in significantly increased external rotation
      and translation compared with the intact condition (P < .05), as well as an
      anterior shift of the humeral head apex at all points of external rotation. Both
      the modified Bristow procedure and soft-tissue Bristow procedure maintained the
      increase in external rotation but resulted in significantly decreased translation
      (P < .05). There was no difference in translation between the 2 reconstructions.
      CONCLUSIONS: The increase in external rotation suggests that the modified Bristow
      procedure does not initially restrict joint motion. Translational stability can
      be restored in a 20% bone loss model without a bone block, suggesting the
      importance of the soft-tissue sling.

PMID- 24925702
TI  - Increased horizontal shoulder abduction is associated with an increase in
      shoulder joint load in baseball pitching.
AB  - BACKGROUND: Soft tissues of the shoulder undergoes substantial stresses due to
      humeral head movement, and this may contribute to throwing shoulder injuries in
      baseball pitchers. Prevention and management of throwing shoulder injuries
      critically rely on reduction of shear force at the shoulder joint. However, the
      amount and direction of the force applied to the shoulder during the throwing
      motion have not been clarified. The purpose of this study was to analyze forces
      applied to the shoulder during a baseball pitch. METHODS: We performed
      biomechanical analysis of 213 baseball pitchers of various ages and skill levels.
      Throwing motion was analyzed with a 3-dimensional motion capture system. The
      Euler angle sequence was adopted to describe angular values of the upper arm
      relative to the trunk for shoulder rotation, and inverse dynamics was used to
      estimate the resultant joint forces at the shoulder. RESULTS: There was a
      significant relation between horizontal abduction/adduction angle and resultant
      anterior/posterior force at the point of maximum external rotation (MER) (r = 
      0.63, P < .01), whereby increased horizontal abduction was associated with
      increased resultant anterior force. There was a significant but weak correlation
      between abduction/adduction angle and superior/inferior force at MER (r = 0.24, P
      < .01). Comparison among the groups with variable ages and skill levels showed
      larger horizontal abduction and smaller external rotation angles at MER in the
      adult amateur player group, whereas normalized compression force and internal
      rotation torque values at MER were smaller in the junior high school- and
      elementary school-aged groups. DISCUSSION: These results suggest that excessive
      horizontal abduction at MER increases anterior shear force in the shoulder and
      may lead to shoulder injuries. Focusing on reducing horizontal abduction at MER
      in the throwing motion may be key to preventing and managing shoulder injuries in
      baseball pitchers.

PMID- 24925703
TI  - Clinical advantages of cartilage palisades over temporalis fascia in type I
      tympanoplasty.
AB  - OBJECTIVE: To compare the post-operative outcomes in using temporalis fascia and
      full thickness broad cartilage palisades as graft in type I tympanoplasty.
      METHODS: This study, conducted at a tertiary referral institute, included 90
      consecutive patients with mucosal type chronic otitis media requiring type I
      tympanoplasty with a 60/30 distribution of cases with fascia and cartilage
      palisades, respectively. The fascia group consisted of primary cases in adults
      and excluded revision cases, near-total or total perforations and pediatric
      cases. The cartilage group included pediatric, revision cases and near-total or
      total perforations. The fascia group utilized the underlay technique for
      grafting, whereas the cartilage group used tragal full thickness broad cartilage
      palisades with perichondrium attached on one side placed in an underlay or over
      underlay manner. Post-operative graft take-up and hearing outcomes were evaluated
      after 6 months and 1 year with subjective assessment and pure tone audiometry.
      RESULTS: The graft take-up rate was 83.3% in the fascia group and 90% in the
      cartilage palisade group. The mean pure tone air-bone gaps pre- and post
      operatively in the fascia group were 30.43 +/- 5.75 dB and 17.5 +/- 6.94 dB,
      respectively, whereas for the cartilage group, these values were 29 +/- 6.21 dB
      and 7.33 +/- 3.88 dB, respectively. CONCLUSION: Cartilage grafting with full
      thickness palisades is more effective than fascia as graft material, particularly
      in "difficult" tympanoplasties fraught with higher failure rates otherwise.

PMID- 24925704
TI  - Modified radical neck dissection for residual neck disease after radiotherapy of
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: Although radical neck dissection is proposed as a standard salvage
      procedure for the management of radiotherapy-resistant nasopharyngeal carcinoma
      of the neck, modified radical neck dissection may be appropriate for select
      patients. This study was designed to evaluate the efficacy of individualized neck
      dissections based on preoperative imaging studies and intraoperative exploration
      for the management of radiotherapy-resistant nasopharyngeal carcinoma of the
      neck. METHODS: The study included 42 consecutive patients who failed radiotherapy
      or chemo-radiotherapy for nasopharyngeal carcinoma of the neck and underwent a
      total of 46 radical neck dissections or modified radical neck dissections.
      Selection of the proper type of neck dissection was based on preoperative imaging
      studies and intraoperative exploration. The patients' clinical features,
      pathologic characteristics, complications, and treatment outcome were estimated
      and analyzed. RESULTS: Radical neck dissection and modified radical neck
      dissection were performed on 19 and 27 necks, respectively. Thirty-three necks
      (71.7%) had multiple node metastases. Nineteen necks (41.3%) had node metastases
      at two or more levels. The overall morbidity rate was 11.9%. The 5-year neck
      control rate (NCR) was 79.1% for 46 necks. The 5-year overall survival and
      disease free survival for 42 patients were 58.0% and 44.0%, respectively. No
      statistically significant differences were found in comparing OS, DFS, NCR
      between the MRND and RND groups. CONCLUSIONS: Individualized neck dissection
      based on preoperative imaging studies and intraoperative exploration is
      appropriate for the management of radiotherapy-resistant nasopharyngeal carcinoma
      of the neck.

PMID- 24925706
TI  - The spatial distribution of errors made by rats in Hebb-Williams type mazes in
      relation to the spatial properties of the blind alleys.
AB  - The various configurations in series of Hebb-Williams type of mazes, which are
      used to measure problem solving behaviour in rats, differ markedly in structure.
      The relationship between error behaviour and spatial maze structure in control
      rats tested in a number of pharmacological experiments is described in this
      paper. The spatial structure of error behaviour of rats was found to correlate
      with maze structure. Knowledge of these correlations can be used to predict error
      patterns in new mazes. Furthermore, aspecific experience acquired by running in a
      number of different configurations, affected error behaviour in a particular test
      configuration. This effect of aspecific experience was different from that of
      specific experience acquired in the same test configuration. In studies
      investigating effects of (e.g. pharmacological) treatments on maze behaviour of
      rats, changes in the structure of errors may be useful to determine the nature of
      the behavioural alterations. 

PMID- 24925705
TI  - High-fat diet induces early-onset diabetes in heterozygous Pax6 mutant mice.
AB  - BACKGROUND: Type 2 diabetes is caused by interactions between genetic and
      environmental factors. Our previous studies reported that paired box 6 mutation
      heterozygosity (Pax6(m/+)) led to defective proinsulin processing and subsequent
      abnormal glucose metabolism in mice at 6  months of age. However, high-fat diet
      exposure could be an important incentive for diabetes development. In this study,
      we aimed to develop a novel diabetic model imitating human type 2 diabetes by
      exposing Pax6(m/+) mice to high-fat diet and to explore the underlying mechanism
      of diabetes in this model. METHODS: Over 300 Pax6(m/+) and wild-type male
      weanling mice were randomly divided into two groups and were fed an high-fat diet
      or chow diet for 6-10  weeks. Blood glucose and glucose tolerance levels were
      monitored during this period. Body weights, visceral adipose weights, blood lipid
      profiles and insulin sensitivity (determined with an insulin tolerance test) were
      used to evaluate obesity and insulin resistance. Proinsulin processing and
      insulin secretion levels were used to evaluate pancreatic beta cell function.
      RESULTS: After 6  weeks of high-fat diet exposure, only the Pax6(m/+) mice showed
      dramatic postloading hyperglycaemia. These mice exhibited significant high-fat
      diet-induced visceral obesity and insulin resistance and displayed defective
      prohormone convertase 1/3 production, an increased proinsulin:total insulin ratio
      and impaired early-phase insulin secretion, because of the Pax6 mutation.
      Hyperglycaemia worsened progressively over time with the high-fat diet, and most
      Pax6(m/+) mice on high-fat diet developed diabetes or impaired glucose tolerance
      after 10  weeks. Furthermore, high-fat diet withdrawal partly improved blood
      glucose levels in the diabetic mice. CONCLUSIONS: By combining the Pax6(m/+)
      genetic background with an high-fat diet environment, we developed a novel
      diabetic model to mimic human type 2 diabetes. This model is characterized by
      impaired insulin secretion, caused by the Pax6 mutation, and high-fat diet
      induced insulin resistance and therefore provides an ideal tool for research on
      type 2 diabetes pathogenesis and therapies.

PMID- 24925707
TI  - Role of dam and pups in the absence of nursing in CPB-B rats (rattus norvegicus).
AB  - In rats of the CPB-B strain, the female shows normal parturition behaviour and
      normal capacity of milk secretion, but the young - all born alive - die within
      few days of birth. Here, we report that this postnatal mortality is eliminated
      when CPB-B neonates are crossfostered to mothers of the Wu:Cpb strain;
      conversely, Wu:Cpb neonates (which are successfully reared by dams of their own
      strain) die within few days of birth when crossfostered to newly parturient CPB-B
      rats. It is suggested that pup mortality in CPB-B rats is due to inadequate
      maternal care resulting, supposedly, from susceptibility of the mother to
      disturbing environmental stimuli. 

PMID- 24925708
TI  - Social and spatial structure in brook chars (Salvelinus fontinalis) under
      competition for food and shelter/shade.
AB  - Salmonids, outside their reproductive period, are seen to have two types of
      territory called "territorial mosaic" and "partial territory". The first aspect
      of this research aimed at identifying the type of territory established by mature
      brook chars in artificial streams. After this, the biological value of spacing
      out was studied with regard to two resources: food, and shelter/shade which gives
      protection. Three 5 X 1 X 1 m artificial streams were built on the edge of a
      natural brook which provided a continuous water supply. One hundred and fifty
      mature brook chars (Salvelinus fontinalis) taken from that brook were distributed
      into 30 colonies with 5 members apiece. Three experimental conditions were
      created, and 10 colonies were submitted to each of these. In the first
      experimental condition, the quality of shelter/shade differed in 3 sectors of the
      artificial streams, whereas the quantity of food remained the same for all 3. In
      the second experimental condition, the quality of shelter/shade was identical,
      while the quantity of food differed in the 3 sectors. In the last condition,
      conflict was created: the fish had to choose between an area which offered
      excellent shelter/shade but no food, one which provided ample nourishment but no
      shelter/shade, and one in which all those resources were present at intermediate
      levels. Observation of the 30 colonies revealed "partial territory" in all cases.
      These corresponded to more or less complete aggressive-dominance hierarchies.
      Almost every alpha established territory, and the number of territorial
      individuals progressively decreased throughout inferior ranks. Alphas had
      exclusive use of their territory. Lower-ranking individuals successfully defended
      their territory against their subordinates, but were unable to drive away higher
      ranking conspecifics. Overall results also indicated that the highest- ranking
      brook chars in the aggressive-dominance hierarchies more frequently established
      their territories in sectors of the streams with good shelter/shade than in
      sectors with good alimentary conditions. 

PMID- 24925709
TI  - Ethanol effects on freezing and conspecific attack in rats previously exposed to
      a cat.
AB  - Male rats under saline or three levels of ethanol were briefly exposed to a cat
      or to a control stimulus and then presented with a male conspecific in the same
      ssituation. Cat exposure produced prolonged freezing and a suppression of
      aggression for the saline group. However, while groups receiving ethanol showed a
      systematic and reliable reduction in freezing as a function of increasing dose
      levels, male attack behavior did not show a corresponding (opposite) set of
      changes: Although freezing was reliably reduced at 0.6 and 1.2 g/kg ethanol an
      increase in offensive behavior at the 0.6 dose level was not reliable, while
      offense reliably declined at the higher level. Correlations between freezing
      changes and offense were significant only for the 0.3 g/kg dose level groups, for
      which neither freezing nor attack was reliably different from the saline level.
      The partial disassociation of freezing and the suppression of male attack on a
      conspecific is not congruent with a view that the effects of ethanol on
      aggression are mediated by an ethanol-based suppression of fear. However, these
      results do suggest that the offense and fear-related changes may be linked at
      very low ethanol doses. 

PMID- 24925710
TI  - Short-term and long-term habituation of exploration in rats, hamsters and
      gerbils.
AB  - Short-term (within-session) and long-term (between-session) habituation of
      exploratory behavior was studied in rats, hamsters and gerbils. Subjects were
      observed in an open field containing four different objects during three 15-min
      sessions with an 8-14 h interval between each session. Their exploratory activity
      was measured by the numbers of contacts they made with these objects. The three
      species differed from each other in both their long-term and short-term
      habituation of exploration. Rats showed disrupted between-session habituation
      because of an important initial burst of activity at the beginning of each
      session. In contrast, hamsters and gerbils displayed between-session habituation,
      but within-session habituation occured during the first session only. These
      results are discussed in relation both to the adaptive value of exploration, and
      to the natural habitat of each species. 

PMID- 24925711
TI  - Acquisition and social communication of stimulus recognition by Fish.
AB  - In fish, behavior commonly designated as Pavlovian and/or instrumental
      conditioning, imprinting, and social learning often appears to reflect a
      phylogenetically adapted operation of a single underlying learning mechanism, a
      version of stimulus substitution. In this mechanism, a releasing stimulus comes
      to share control over the release of behavior with a previously neutral stimulus.
      In addition, control over the direction of released responses is simultaneously
      transferred. The outcome, as supported by review of the literature, is that
      recognition learning in fish seems to involve primarily the extension to new
      stimuli of control over the elicitation of preorganized unlearned responses. 

PMID- 24925712
TI  - Lack of a clinically important pharmacokinetic interaction between sofosbuvir or
      ledipasvir and hormonal oral contraceptives norgestimate/ethinyl estradiol in HCV
      uninfected female subjects.
AB  - This study evaluated the potential for a drug-drug interaction between HCV direct
      acting antivirals sofosbuvir or ledipasvir and oral hormonal contraceptive (OC)
      norgestimate/ethinyl estradiol (norgestimate 0.18/0.215/0.25 mg with ethinyl
      estradiol 25 MUg). This was a 112-day, open-label, fixed-sequence pharmacokinetic
      (PK) study in healthy female subjects that included a lead-in cycle (OC only; N =
      21), cycle 1 (OC only; N = 15), cycle 2 (OC + sofosbuvir; N = 15), and cycle 3
      (OC + ledipasvir; N = 15). Administration of sofosbuvir with OC did not alter PK
      of norelgestromin (primary norgestimate metabolite) or ethinyl estradiol. Small
      increases in norgestrel (secondary norgestimate metabolite) AUC(tau) (19%) and
      C(tau) (23%) with sofosbuvir were noted. Ledipasvir did not impact PK of
      norelgestromin or norgestrel but modestly increased ethinyl estradiol C(max)
      (40%). Sofosbuvir, GS- 331007 (predominant circulating metabolite of SOF), and
      ledipasvir PK were similar to historical data. Pharmacodynamic markers
      luteinizing hormone, follicle-stimulating hormone, and progesterone values were
      generally comparable in all cycles. No loss in contraceptive efficacy is expected
      upon administration of sofosbuvir or ledipasvir/sofosbuvir with oral
      contraceptives containing norgestimate and ethinyl estradiol. The use of
      sofosbuvir or ledipasvir/sofosbuvir FDC with oral contraceptives is permitted.

PMID- 24925714
TI  - What do Australian Women Experiencing Intimate Partner Abuse Want From Family and
      Friends?
AB  - We analyzed the views of a diverse sample of women (N = 254) living in the state
      of Victoria, Australia, who were experiencing fear of an intimate partner. We
      explored the women's views about their interactions with their family and friends
      to examine what women who have experienced fear of a partner or ex-partner want
      from their family and friends. The themes identified provide potentially useful
      guidance for what might be helpful and unhelpful communication strategies and
      behaviors for families and friends. Women experiencing intimate partner abuse
      find informal support invaluable, provided it is delivered in a helpful fashion.
      Helpful support is affirming, encouraging, validating, and understanding, and
      delivered with positive regard, empathy, and respect. Social contact and
      interaction are particularly appreciated, as is instrumental support such as
      financial help, housing, and child care. Women value both support that is
      directly related to abuse and support related to other areas of life.

PMID- 24925713
TI  - Effect of docosahexaenoic acid-enriched fish oil supplementation in pregnant
      women with Type 2 diabetes on membrane fatty acids and fetal body composition-
      double-blinded randomized placebo-controlled trial.
AB  - AIMS: To test if docosahexaenoic acid-enriched fish oil supplementation rectifies
      red cell membrane lipid anomaly in pregnant women with Type 2 diabetes and their
      neonates, and alters fetal body composition. METHODS: Women with Type 2 diabetes
      (n = 88; 41 fish oil, 47 placebo) and healthy women (n = 85; 45 fish oil, 40
      placebo) were supplemented from the first trimester until delivery. Blood fatty
      acid composition, fetal biometric and neonatal anthropometric measurements were
      assessed. RESULTS: A total of 117 women completed the trial. The women with Type
      2 diabetes who took fish oil compared with those who received placebo had higher
      percentage of docosahexaenoic acid in red cell phosphatidylethanolamine in the
      third trimester (12.0% vs. 8.9%, P = 0.000) and at delivery (10.7% vs. 7.4%, P =
      0.001). Similarly, the neonates of the women with Type 2 diabetes supplemented
      with the fish oil had increased docosahexaenoic acid in the red cell
      phosphatidylethanolamine (9.2% vs. 7.7%, P = 0.027) and plasma
      phosphatidylcholine (6.1% vs. 4.7%, P = 0.020). Docosahexaenoic acid-rich fish
      oil had no effect on the body composition of the fetus and neonates of the women
      with Type 2 diabetes. CONCLUSIONS: A daily dose of 600 mg of docosahexaenoic acid
      was effective in ameliorating red cell membrane docosahexaenoic acid anomaly in
      pregnant women with Type 2 diabetes and neonates, and in preventing the decline
      of maternal docosahexaenoic acid during pregnancy. We suggest that the provision
      of docosahexaenoic acid supplement should be integrated in the antenatal care of
      pregnant women with Type 2 diabetes.

PMID- 24925716
TI  - Reply: To PMID 24715615.

PMID- 24925717
TI  - Economic feasibility study for improving drinking water quality: a case study of
      arsenic contamination in rural Argentina.
AB  - Economic studies are essential in evaluating the potential external investment
      support and/or internal tariffs available to improve drinking water quality. Cost
      benefit analysis (CBA) is a useful tool to assess the economic feasibility of
      such interventions, i.e. to take some form of action to improve the drinking
      water quality. CBA should involve the market and non-market effects associated
      with the intervention. An economic framework was proposed in this study, which
      estimated the health avoided costs and the environmental benefits for the net
      present value of reducing the pollutant concentrations in drinking water. We
      conducted an empirical application to assess the economic feasibility of removing
      arsenic from water in a rural area of Argentina. Four small-scale methods were
      evaluated in our study. The results indicated that the inclusion of non-market
      benefits was integral to supporting investment projects. In addition, the
      application of the proposed framework will provide water authorities with more
      complete information for the decision-making process. 

PMID- 24925718
TI  - Are post-trial observational studies useful?

PMID- 24925720
TI  - Renal ApoA-1 amyloidosis with Glu34Lys mutation and intra-amyloid lipid
      accumulation.
AB  - Apolipoprotein A-1 (ApoA-1) amyloidosis occurs as a nonhereditary condition in
      atherosclerotic plaques, but it can also manifest as a hereditary disorder caused
      by mutations of the APOA1 gene. Hereditary ApoA-1 amyloidosis presents with
      diverse organ involvement based on the position of the mutation. We describe a
      case of ApoA-1 amyloidosis with a Glu34Lys mutation; testicular, conjunctival,
      and renal involvement; and the notable finding of lipid deposition within the
      amyloid deposits.

PMID- 24925719
TI  - Predictors of autosomal dominant polycystic kidney disease progression.
AB  - Autosomal dominant polycystic kidney disease is a genetic disorder associated
      with substantial variability in its natural course within and between affected
      families. Understanding predictors for rapid progression of this disease has
      become increasingly important with the emergence of potential new treatments.
      This systematic review of the literature since 1988 evaluates factors that may
      predict and/or effect autosomal dominant polycystic kidney disease progression.
      Predicting factors associated with early adverse structural and/or functional
      outcomes are considered. These factors include PKD1 mutation (particularly
      truncating mutation), men, early onset of hypertension, early and frequent gross
      hematuria, and among women, three or more pregnancies. Increases in total kidney
      volume and decreases in GFR and renal blood flow greater than expected for a
      given age also signify rapid disease progression. Concerning laboratory markers
      include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin
      levels in affected adults. These factors and others may help to identify patients
      with autosomal dominant polycystic kidney disease who are most likely to benefit
      from early intervention with novel treatments. 

PMID- 24925721
TI  - Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte
      injury phenotypes in glomerular disease.
AB  - Diabetic kidney disease (DKD) is the most common cause of ESRD in the United
      States. Podocyte injury is an important feature of DKD that is likely to be
      caused by circulating factors other than glucose. Soluble urokinase plasminogen
      activator receptor (suPAR) is a circulating factor found to be elevated in the
      serum of patients with FSGS and causes podocyte alphaVbeta3 integrin-dependent
      migration in vitro. Furthermore, alphaVbeta3 integrin activation occurs in
      association with decreased podocyte-specific expression of acid sphingomyelinase
      like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with
      FSGS. However, whether suPAR-dependent alphaVbeta3 integrin activation occurs in
      diseases other than FSGS and whether there is a direct link between circulating
      suPAR levels and SMPDL3b expression in podocytes remain to be established. Our
      data indicate that serum suPAR levels are also elevated in patients with DKD.
      However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from
      patients with DKD and DKD sera-treated human podocytes, where it prevented
      alphaVbeta3 integrin activation by its interaction with suPAR and led to
      increased RhoA activity, rendering podocytes more susceptible to apoptosis. In
      vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD
      but not FSGS, indicating that SMPDL3b expression levels determined the podocyte
      injury phenotype. These observations suggest that SMPDL3b may be an important
      modulator of podocyte function by shifting suPAR-mediated podocyte injury from a
      migratory phenotype to an apoptotic phenotype and that it represents a novel
      therapeutic glomerular disease target. 

PMID- 24925722
TI  - Renal outcomes in patients with type 1 diabetes and macroalbuminuria.
AB  - Macroalbuminuria, defined as urine albumin excretion rate (AER)>=300 mg/d, has
      long been considered a stage of irreversible kidney damage that leads reliably to
      GFR loss. We examined the long-term renal outcomes of persons with type 1
      diabetes who developed incident macroalbuminuria during the Diabetes Control and
      Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and
      Complications (EDIC) study. One hundred fifty-nine participants developed
      incident macroalbuminuria and were subsequently followed for a median duration of
      9 years (maximum of 25 years). At the time of macroalbuminuria diagnosis, mean
      (SD) age was 37 (9) years, mean (SD) duration of diabetes was 17 (5) years,
      median AER was 524 mg/d, and mean (SD) eGFR was 108 (20) ml/min per 1.73 m(2).
      Ten years after macroalbuminuria diagnosis, the cumulative incidence of a
      sustained reduction in AER to <300 mg/d was 52%, mostly but not entirely under
      treatment with renin-angiotensin system inhibitors. The cumulative incidence of
      impaired GFR (sustained eGFR<60 ml/min per 1.73 m(2)) 10 years after
      macroalbuminuria diagnosis was 32%, including 16% who developed ESRD. Lower
      hemoglobin A1c and BP and regression to AER<300 mg/d were associated with reduced
      risk of developing impaired GFR. In conclusion, people with type 1 diabetes who
      develop macroalbuminuria are at high risk of progressive kidney disease. However,
      through at least 10 years of follow-up, AER could often be controlled, and GFR
      frequently remained in the normal range. 

PMID- 24925723
TI  - Neighborhood socioeconomic status, race, and mortality in young adult dialysis
      patients.
AB  - Young blacks receiving dialysis have an increased risk of death compared with
      whites in the United States. Factors influencing this disparity among the young
      adult dialysis population have not been well explored. Our study examined the
      relation of neighborhood socioeconomic status (SES) and racial differences in
      mortality in United States young adults receiving dialysis. We merged US Renal
      Data System patient-level data from 11,027 black and white patients ages 18-30
      years old initiating dialysis between 2006 and 2009 with US Census data to obtain
      neighborhood poverty information for each patient. We defined low SES
      neighborhoods as those neighborhoods in U.S. Census zip codes with >=20% of
      residents living below the federal poverty level and quantified race differences
      in mortality risk by level of neighborhood SES. Among patients residing in low
      SES neighborhoods, blacks had greater mortality than whites after adjusting for
      baseline demographics, clinical characteristics, rurality, and access to care
      factors. This difference in mortality between blacks and whites was significantly
      attenuated in higher SES neighborhoods. In the United States, survival between
      young adult blacks and whites receiving dialysis differs by neighborhood SES.
      Additional studies are needed to identify modifiable factors contributing to the
      greater mortality among young adult black dialysis patients residing in low SES
      neighborhoods.

PMID- 24925724
TI  - Integrative biology identifies shared transcriptional networks in CKD.
AB  - A previous meta-analysis of genome-wide association data by the Cohorts for Heart
      and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16
      loci associated with eGFR. To define how each of these single-nucleotide
      polymorphisms (SNPs) could affect renal function, we integrated GFR-associated
      loci with regulatory pathways, producing a molecular map of CKD. In kidney biopsy
      specimens from 157 European subjects representing nine different CKDs, renal
      transcript levels for 18 genes in proximity to the SNPs significantly correlated
      with GFR. These 18 genes were mapped into their biologic context by testing
      coregulated transcripts for enriched pathways. A network of 97 pathways linked by
      shared genes was constructed and characterized. Of these pathways, 56 pathways
      were reported previously to be associated with CKD; 41 pathways without prior
      association with CKD were ranked on the basis of the number of candidate genes
      connected to the respective pathways. All pathways aggregated into a network of
      two main clusters comprising inflammation- and metabolism-related pathways, with
      the NRF2-mediated oxidative stress response pathway serving as the hub between
      the two clusters. In all, 78 pathways and 95% of the connections among those
      pathways were verified in an independent North American biopsy cohort. Disease
      specific analyses showed that most pathways are shared between sets of three
      diseases, with closest interconnection between lupus nephritis, IgA nephritis,
      and diabetic nephropathy. Taken together, the network integrates candidate genes
      from genome-wide association studies into their functional context, revealing
      interactions and defining established and novel biologic mechanisms of renal
      impairment in renal diseases. 

PMID- 24925727
TI  - Interplay of disorder and antiferromagnetism in TlFe(1.6+delta)(Se(1-x)S(x))2
      probed by neutron scattering.
AB  - The effect of selenium substitution by sulphur on the structural and physical
      properties of antiferromagnetic TlFe1.6+deltaSe2 has been investigated via
      neutron, x-ray and electron diffraction, and transport measurements. The
      ?5a*?5a*c super-cell related to the iron vacancy ordering found in the pure
      TlFe1.6Se2 selenide is also present in the S-doped TlFe1.6+delta(Se1-xSx)2
      compounds. Neutron scattering experiments show the occurrence of the same long
      range magnetic ordering in the whole series i.e. the 'block checkerboard'
      antiferromagnetic structure. In particular, this is the first detailed study
      where the crystal structure and the ?5a*?5a antiferromagnetic structure is
      characterized by neutron powder diffraction for the pure TlFe1.6+deltaS2 sulphide
      over a large temperature range. We demonstrate the strong correlation between
      occupancies of the crystallographic iron sites, the level of iron vacancy
      ordering and the occurrence of block antiferromagnetism in the sulphur series.
      Introducing S into the Se sites also increases the Fe content in
      TlFe1.6+delta(Se1-xSx)2 which in turn leads to the disappearance of the Fe
      vacancy ordering at x = 0.5 +/- 0.15. However, by reducing the nominal Fe
      content, the same ?5a*?5a*c vacancy ordering and antiferromagnetic order can be
      recovered also in the pure TlFe1.6+deltaS2 sulphide with a simultaneous reduction
      in the Neel temperature from 435 K in the selenide TlFe1.75Se2 to 330 K in the
      sulphide TlFe1.5S2. The magnetic moment remains high at low temperature
      throughout the full substitution range, which contributes to the absence of
      superconductivity in these compounds.

PMID- 24925725
TI  - Lupus nephritis susceptibility loci in women with systemic lupus erythematosus.
AB  - Lupus nephritis is a manifestation of SLE resulting from glomerular immune
      complex deposition and inflammation. Lupus nephritis demonstrates familial
      aggregation and accounts for significant morbidity and mortality. We completed a
      meta-analysis of three genome-wide association studies of SLE to identify lupus
      nephritis-predisposing loci. Through genotyping and imputation, >1.6 million
      markers were assessed in 2000 unrelated women of European descent with SLE (588
      patients with lupus nephritis and 1412 patients with lupus without nephritis).
      Tests of association were computed using logistic regression adjusting for
      population substructure. The strongest evidence for association was observed
      outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2;
      P=4.5*10(-7)), 16p12 (SLC5A11; P=5.1*10(-7)), 6p22 (ID4; P=7.4*10(-7)), and
      8q24.12 (HAS2, SNTB1; P=1.1*10(-6)). Both HLA-DR2 and HLA-DR3, two well
      established lupus susceptibility loci, showed evidence of association with lupus
      nephritis (P=0.06 and P=3.7*10(-5), respectively). Within the class I region,
      rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus
      nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5*10(-6)). Consistent with a
      functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and
      associated pathway members showed significant enrichment in patients with lupus
      nephritis (n=32) compared with controls (n=15). Results from this large-scale
      genome-wide investigation of lupus nephritis provide evidence of multiple
      biologically relevant lupus nephritis susceptibility loci.

PMID- 24925728
TI  - Eleven-year trends in gender differences of treatments and mortality in ST
      elevation acute myocardial infarction in northern Italy, 2000 to 2010.
AB  - The aim of this study was to assess recent trends in hospital mortality and in
      the treatment techniques for patients with ST-segment elevation myocardial
      infarction according to gender. Data on hospitalizations for ST-segment elevation
      myocardial infarction from 2000 to 2010 were extracted from hospital discharge
      record databases (International Classification of Diseases, Ninth Revision,
      Clinical Modification, codes) in the Lombardy Region of Italy. The impact of
      female gender on in-hospital mortality was assessed by multivariable regression
      after adjusting for invasive approach use (i.e., coronary angiography,
      angioplasty or coronary artery bypass graft), age, and co-morbidities. A total of
      89,562 patients, men (66.5%) and women (33.5%), were enrolled. The use of an
      invasive approach increased over time in both sexes although it was higher in men
      (from 54.9% in 2000 to 91.9% in 2010 in men; from 36.8% in 2000 to 72.0% in 2010
      in women). This pattern was driven by the subgroup of patients aged >=75 years,
      whereas differences between sexes were not observed in patients <65 years and
      were small in patients aged 65 to 74 years. In-hospital mortality presented a
      small decrease from 7.6% in 2000 to 6.2% in 2010 in men (p for trend = 0.004),
      whereas it remained higher and substantially constant over time in women (16.6%
      in 2000, 15.5% in 2010, p for trend = 0.09). At multivariable regression, female
      gender did not emerge as an independent predictor of mortality (p = 0.13).
      However, a significant gender-age interaction was found, with female gender being
      a significant predictor of increased mortality in patients aged >=75 years (odds
      ratio [OR] 1.33) while predicting a reduced mortality in patients aged <75 years
      (OR 0.93, p for interaction <0.0001). The use of an invasive approach was an
      independent predictor of mortality (OR 0.23, p <0.0001), the magnitude of
      mortality reduction being higher in men than in women and in patients aged <75
      years than in those aged >=75 years. In conclusion, a weak temporal trend in
      mortality reduction is observed in men only, which is driven by patients aged
      >=75 years. In-hospital mortality remains higher in women than in men, although
      female gender is not a significant predictor of mortality. Despite temporal
      increases in the use of an invasive approach, women are more often treated
      conservatively. 

PMID- 24925729
TI  - Susceptibility-weighted imaging in pediatric neuroimaging.
AB  - Susceptibility-weighted imaging (SWI) has become a key MR sequence in pediatric
      neuroimaging. The usage of SWI has significantly expanded recently. The strength
      of SWI lies not just in its ability to identify hemorrhage, calcium or nonheme
      iron by virtue of its susceptibility artifact, but also more importantly, the
      blood oxygen level dependent venography principle whereby several diseases can be
      diagnosed earlier. We are continuing to harness the power of SWI in the field of
      pediatric neuroimaging. In this paper, we will make a comprehensive review and
      discuss the utility of SWI in pediatric neuroimaging in establishing the
      diagnosis, differential diagnosis, and also understanding the pathomechanism of
      various pediatric brain pathologies.

PMID- 24925726
TI  - Regulated cell death in AKI.
AB  - AKI is pathologically characterized by sublethal and lethal damage of renal
      tubules. Under these conditions, renal tubular cell death may occur by regulated
      necrosis (RN) or apoptosis. In the last two decades, tubular apoptosis has been
      shown in preclinical models and some clinical samples from patients with AKI.
      Mechanistically, apoptotic cell death in AKI may result from well described
      extrinsic and intrinsic pathways as well as ER stress. Central converging nodes
      of these pathways are mitochondria, which become fragmented and sensitized to
      membrane permeabilization in response to cellular stress, resulting in the
      release of cell death-inducing factors. Whereas apoptosis is known to be
      regulated, tubular necrosis was thought to occur by accident until recent work
      unveiled several RN subroutines, most prominently receptor-interacting protein
      kinase-dependent necroptosis and RN induced by mitochondrial permeability
      transition. Additionally, other cell death pathways, like pyroptosis and
      ferroptosis, may also be of pathophysiologic relevance in AKI. Combination
      therapy targeting multiple cell-death pathways may, therefore, provide maximal
      therapeutic benefits.

PMID- 24925730
TI  - A robust molecular pattern for myelodysplastic syndromes in two independent
      cohorts investigated by next-generation sequencing can be revealed by comparative
      bioinformatic analyses.

PMID- 24925731
TI  - Photoreceptor layer thinning in parkinsonian syndromes.

PMID- 24925732
TI  - Calcium binding protein calretinin (29kD) localization in the forebrain of the
      cichlid fish: An immunohistochemical study.
AB  - Ionic regulation is essential for the metabolism and cellular function. For many
      physiological processes, ionic calcium (Ca(+2)) is important for example muscle
      contractions, nerve signaling, membrane permeability, cell division and hormone
      release. In nerve cells, the excess intracellular concentration of Ca(+2) causes
      cell death. It has been shown that certain calcium binding proteins (CaBPs) are
      essential for Ca(+2) homeostasis and protect neurons from excess Ca(+2) influx.
      We are for the first time showing an unusual calretinin (CR) expression and
      significant differences in its occurrence in the forebrain of the cichlid fish
      (Cynotilapia sp.) compared to other teleosts. CR labeled neurons were seen in the
      dorsal and lateral part of the dorsal telencephalic area, entopeduncular nucleus
      (EN), nucleus preopticus (NPO), diffuse nucleus of lateral torus (NDTL), ventral
      hypothalamic nucleus (VH), preglomerular nucleus (NPG) and optic tectum.
      Surprisingly, large numbers of CR immunoreactive perikarya were noted in the
      optic chiasma (Oc). These neurons were oval with elongated processes and forming
      a huge fiber network in the Oc. Enormously CR stained fibers were seen in the
      lateral and medial olfactory tract. Widespread distributions of strongly CR
      labeled fibers were observed around the EN projecting dorsally into the
      telencephalon, Oc and optic nerve. Presence of CR in the NPO suggests that it may
      be involved in the hormonal regulation by the pituitary. As in vertebrates EN
      plays an important role in sensory functions, massive localization CR in the EN
      may suggests role of CR in sensory functions of the cichlid fish. 

PMID- 24925733
TI  - A retrospective descriptive study of oral azole antifungal agents in patients
      with patch test-negative head and neck predominant atopic dermatitis.
AB  - BACKGROUND: Head and neck dermatitis is a subtype of atopic dermatitis driven by
      Malassezia yeast. OBJECTIVE: We sought to evaluate the response of these patients
      to systemic azole antifungals. METHODS: We queried the electronic medical records
      from our institution for patients that were referred for allergy patch testing,
      were ultimately given the diagnosis of head and neck dermatitis, and were treated
      with oral azole antifungals over a 2-year period. RESULTS: Twenty-four patients
      met inclusion criteria and were analyzed. Most patients noted their
      characteristic flare beginning during their teenage, young adult, or adult years.
      All were noted to have some involvement of the head and neck, and 17 responded to
      treatment. The mean time taking an azole antifungal medication was 8 months, with
      a mean overall follow-up of 10 months. LIMITATIONS: This was a retrospective
      descriptive study, from a single institution, of a limited number of patients,
      and did not use a validated scoring system. CONCLUSION: Itraconazole and other
      azole antifungals were an effective treatment for more than two-thirds of adult
      patients with head and neck predominant atopic dermatitis.

PMID- 24925734
TI  - Spectrum and impact of health problems during deployment: a prospective,
      multicenter study of French soldiers operating in Afghanistan, Lebanon and Cote
      d'Ivoire.
AB  - BACKGROUND: More than 15 000 French soldiers are continuously deployed abroad.
      Along with combat-related injuries, they are exposed to non-combat-related
      diseases with an underestimated burden. Our objectives were to assess the
      incidence and impact of health problems on their operating capacity. METHODS: A
      prospective multicenter study was conducted over more than three months in
      Lebanon, Cote d'Ivoire and Afghanistan including exclusively French soldiers.
      RESULTS: We collected 4349 consultations (Afghanistan {n = 719}, Lebanon {n =
      1401} and Cote d'Ivoire {n = 2229}) encompassing 4600 health problems. Injuries
      (21%), diarrhea (19%), dermatoses (17.5%) and respiratory tract infections
      (10.45%) were the most frequent health issues. Infectious diseases represented
      41% of all health problems. Almost nine out of ten patients were managed as
      outpatients. Ten combat-related deaths were observed. We reported 68 (1.5%)
      medical repatriations of which 28 and 26 were psychiatric and trauma cases
      respectively. Partial or complete incapacity was estimated 724 days/1000
      men/month. Etiological spectrum was similar in all three countries however, the
      incidence of diarrhea (p < 0.05) as well as inpatient management and medical
      evacuation rates were higher (p < 0.0001) in Afghanistan. CONCLUSIONS: There was
      a wide spectrum of health problems occurring during military deployments with a
      predominance of common infections. Non-combat-related pathology represented an
      important burden for the loss of operating capacity.

PMID- 24925735
TI  - Oral behaviour following forebrain ablations in Gallus Domesticus.
AB  - The oral behaviour of adult Brown Leghorn hens was recorded in response to oral
      stimulation with water, 2 M sodium chloride, 2 M acetic acid and 0.1 M quinine
      hydrochloride before and after surgical ablation of either the anterior
      telencephalon or the entire telencephalon and/or the diencephalon. It was found
      that beak wiping behaviour could be abolished by the removal of the anterior
      telencephalon. Head shaking behaviour was abolished only by the complete removal
      of the forebrain (telencephalon and diencephalon) whereas beak and tongue
      movements persisted after forebrain removal. Although these three behaviour
      patterns occur together in response to the stimulus, they appear to be controlled
      in different areas of the brain. The results are discussed in relation to the
      current work on the control of oral behaviour in mammals. 

PMID- 24925736
TI  - The assessment of fear in domestic hens exposed to a looming human stimulus.
AB  - The behavioural and physiological responses of hens exposed to a slowly
      approaching human being were assessed using remote observation and radio
      telemetry of heart rate. Forty isolated hens of two strains and from two rearing
      environments were used. The sequence of behavioural changes included looking
      around, ceasing feeding, head shaking or complete withdrawal and finally
      crouching or escape behaviour. The heart rate rose from a mean level of 303
      beats/min when the birds were at rest, to 465 beats/min when the cage was opened
      and the bird caught and held at the conclusion of the approach. The light hybrid
      strain showed more pronounced behavioural responses and a greater proportional
      rise in heart rate in the course of the approach than the medium hybrid birds,
      consistent with the induction of a higher level of fear. An environmental effect
      was also observed, pen-reared birds were more disturbed than caged ones. The
      similarity of the time course of the physiological and behavioural measures
      supports the concept of fear as an intervening variable which has simultaneous
      effects on heart rate and behaviour. Both may be effective in assessing fear, and
      they should be regarded as complementary rather than alternative measures. 

PMID- 24925737
TI  - The effects of regular handling on fear responses in the domestic chick.
AB  - Reduction of fear in the domestic chick by regular handling was assessed and an
      attempt was made to determine whether such an effect was due specifically to
      reduced fear of human beings or to a general reduction in fearfulness. Regular
      handling decreased the tonic immobility response, a fear-potentiated phenomenon,
      and increased approach to a human being, but had no effect on approach towards an
      inanimate object. These findings were common to three strains (two layer, one
      broiler), and suggest that handling does not depress general fearfulness, but
      specifically reduces fear of human beings, presumably through habituation. 

PMID- 24925738
TI  - Effects of basolateral or corticomedial amygdaloid lesions on grooming,
      consummatory, and locomotor behaviours in rats.
AB  - Grooming behaviour in rats was induced by limited water access and by water spray
      before and after corticomedial or basolateral amygdaloid lesions or control
      operations. Corticomedial lesions produced some attenuation of grooming induced
      by limited water access but increased grooming induced by water spray.
      Basolateral lesions did not consistently affect grooming. There was an increase
      in ambulation time following basolateral lesions and a relative decrease in
      feeding time following corticomedial lesions. There were no effects of either
      lesion on drinking or rearing. Detailed examination of both grooming and non
      grooming behaviours provided little evidence for lesion induced disruption of
      response sequencing. 

PMID- 24925739
TI  - Attempts to determine the status of electroshock-induced attack in male
      laboratory mice.
AB  - An attempt was made using a combination of simple experimental manipulations and
      videotape recorder (VTR) analysis of bite targets employed to determine whether
      electroshock-induced attack on anosmic opponents in laboratory mice was an
      offensive or a defensive behaviour. VTR analysis suggested that ventral surface
      biting was more evident in this form of attack than in social conflict.
      Individually- and group-housed males showed similar levels of fighting on
      exposure to electroshock, but dominant males from pairs showed greater attack
      than their subordinate partners. Zinc sulphate-induced anosmia, 36 h of food
      deprivation, castration and lithium chloride treatment reduced electroshock
      induced attack. Although significant changes were not obtained, there was some
      evidence that acute treatment with dexamethasone or ACTH augmented this
      behaviour. The direction of these changes is similar to that seen with social
      conflict, and it is suggested that electroshock-induced attack in the mouse
      (unlike the rat) is largely an aggressive offensive behaviour. The high incidence
      of ventral surface biting may be a consequence of the upright postures assumed on
      subjecting the animals to electroshock. 

PMID- 24925744
TI  - The social structure and ecology of elephant shrews Galen B. Rathbun. Paul Parey,
      Hamburg, 1979. 88 pp., DM. 49.00.

PMID- 24925753
TI  - Femtosecond and temperature-dependent picosecond dynamics of ultrafast excited
      state proton transfer in water-dioxane mixtures.
AB  - Synthetic flavylium salts like the 7-hydroxy-4-methylflavylium (HMF) cation have
      been used as prototypes to study the chemistry and photochemistry of
      anthocyanins, the major group of water-soluble pigments in the plant kingdom. In
      this work, a combination of fluorescence upconversion with femtosecond time
      resolution and time-correlated single photon counting (TCSPC) with picosecond
      time resolution have been employed to investigate in details the excited-state
      proton transfer (ESPT) of HMF in water and in binary water/1,4-dioxane mixtures.
      TCSPC measurements as a function of temperature provide activation parameters for
      all of the individual rate constants involved in the proton transfer, including
      those for dissociation and recombination of the geminate excited base-proton pair
      (A*...H(+)) that can be detected in the water/dioxane mixtures (but not in
      water). Unlike the other rate constants, the deprotonation rate constant kd shows
      a non-Arrhenius dependence on temperature in both water and water/dioxane
      mixtures. At low temperatures kd is close to the dielectric relaxation rate of
      the solvent with a barrier of ca. 8 kJ mol(-1), suggesting that the solvent
      reorganization is the rate-limiting step. At higher temperatures (>30  degrees C)
      the proton transfer process is nearly barrierless and solvent-dependent.
      Fluorescence upconversion results in H2O, D2O, and water/dioxane mixtures confirm
      the two-step model for the ESPT of HMF and provide additional details of the
      early events prior to the onset of proton transfer, attributed to conformational
      relaxation and solvent reaccommodation around the initially formed excited state.
      The results are consistent with DFT calculations that indicate that charge
      redistribution occurs after rather than prior to the onset of the ESPT process. 

PMID- 24925752
TI  - Effects of Saskatoon berry powder on monocyte adhesion to vascular wall of leptin
      receptor-deficient diabetic mice.
AB  - HYPOTHESIS: Atherosclerotic cardiovascular complications are the leading cause of
      death in diabetic patients. Monocyte adhesion is an early event for
      atherogenesis. Previous studies demonstrated that dark-skin berries had
      cardiovascular protective effects. We hypothesize that Saskatoon berry (SB)
      powder may reduce monocyte adhesion in leptin receptor-deficient (db/db) diabetic
      mice. METHODS: Wild-type and db/db mice were fed with chow or supplemented with
      SB powder. Anthocyanins in SB powder were identified using mass spectrometry.
      Mouse monocytes were incubated with mouse aorta. Monocyte adhesion was counted
      under microscopy. Inflammatory or metabolic markers in blood or tissue were
      analyzed using immunological or biochemical methods. RESULTS: SB powder
      significantly reduced monocyte adhesion to aorta from diabetic db/db mice
      compared to regular chow. The increased monocyte adhesion to aorta was normalized
      in db/db mice treated with >=5% of SB powder for 4 weeks. Increased contents of
      Nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase-4, heat shock
      factor-1, monocyte chemotactic protein (MCP)-1, intracellular adhesion molecule
      (ICAM)-1, P-selectin, tumor necrosis factor-alpha, plasminogen activator
      inhibitor (PAI)-1 and urokinase plasminogen activator in aorta or heart apex,
      elevated plasma PAI-1 and MCP-1 were detected in db/db mice on chow compared to
      wild-type mice on the same diet; 5% SB powder inhibited the increases of
      inflammatory, fibrinolytic or stress regulators in aorta or heart apex of db/db
      mice. Monocyte adhesion positively correlated with blood glucose, cholesterol,
      body weight, heart MCP-1, PAI-1 or ICAM-1. CONCLUSION: The findings suggest that
      SB powder attenuated monocyte adhesion to aorta of db/db mice, which was
      potentially mediated through inhibiting the inflammatory, stress and/or
      fibrinolyic regulators.

PMID- 24925755
TI  - Psychometric properties and Dutch norm data of the PedsQL Multidimensional
      Fatigue Scale for Young Adults.
AB  - PURPOSE: The aim of this study was to assess internal consistency and construct
      validity (known-groups validity) and to provide Dutch norm data for the Dutch
      Pediatric Quality of Life Inventory Multidimensional Fatigue Scale for Young
      Adults ages 18-30 years (PedsQL fatigue_YA). METHODS: A Dutch sample of 649 young
      adults completed online a sociodemographic questionnaire and the PedsQL
      fatigue_YA including three subscales: general fatigue, sleep/rest fatigue and
      cognitive fatigue (0-100: Higher scores indicate less fatigue symptoms). RESULTS:
      The PedsQL fatigue_YA showed satisfactory to good internal consistency
      (Cronbach's alpha = .70-.94), except for one scale (.68). The mean scale scores
      were 68.23 (SD 19.15) for 'general fatigue,' 67.04 (SD 15.54) for 'sleep/rest
      fatigue' and 74.62 (SD 19.02) for 'cognitive fatigue.' Men reported significantly
      higher scores on 'general fatigue' and 'sleep/rest fatigue' than women. The
      PedsQL fatigue_YA distinguished between healthy young adults and young adults
      with chronic health conditions, with higher scores on all scales in healthy young
      adults than in those with a chronic health condition. CONCLUSION: The results
      demonstrate good psychometric properties of the PedsQL fatigue_YA in a sample of
      Dutch young adults. With the current norms available, it is possible to evaluate
      fatigue in the Netherlands from childhood to adulthood with the PedsQL
      Multidimensional Fatigue Scale.

PMID- 24925754
TI  - Prospectively measured 10-year changes in health-related quality of life and
      comparison with cross-sectional estimates in a population-based cohort of adult
      women and men.
AB  - PURPOSE: To prospectively assess changes in health-related quality of life
      (HRQOL) over 10 years, by age and sex, and to compare measured within-person
      change to estimates of change based on cross-sectional data. METHODS:
      Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item
      short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for
      domain and summary components were calculated for men and women separately,
      stratified by 10-year age groups. Projected changes based on published age- and
      sex-stratified cross-sectional data were also calculated. Mean differences
      between the two methods were then estimated, along with the 95 % credible
      intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1
      %) of the original cohort. Prospectively collected 10-year changes suggested that
      the four physically oriented domains declined in all but the youngest group of
      men and women, with declines in the elderly men exceeding 25 points. The four
      mentally oriented domains tended to improve over time, only showing substantial
      declines in vitality and role emotional in older women, and all four domains in
      older men. Cross-sectional estimates identified a similar pattern of change but
      with a smaller magnitude, particularly in men. Correspondence between the two
      methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over
      much of the life span, but physically oriented HRQOL can decline substantially
      after middle age. Although clinically relevant declines were more evident in
      prospectively collected data, differences in 10-year age increments of cross
      sectional data may be a reasonable proxy for longitudinal changes, at least in
      those under 65 years of age. Results provide additional insight into the natural
      progression of HRQOL in the general population.

PMID- 24925756
TI  - Evaluation of circulating levels of inflammatory and bone formation markers in
      axial spondyloarthritis.
AB  - Studies have demonstrated the important role of bone remodelling and
      osteoimmunology in the progression of inflammatory lesions in axial
      spondyloarthritis (SpA) disease. This study was conducted to evaluate the
      inflammatory response by analysis of the serum levels of pro-inflammatory and new
      bone formation markers in patients with axial SpA who were treated or not treated
      with anti-tumour necrosis factor-alpha (anti-TNF-alpha) or non-steroidal drugs
      (NSAIDs) and to identify whether these drugs modify the activity and severity of
      the disease. The serum levels of myeloperoxidase (MPO), adenosine deaminase
      (ADA), nitric oxide metabolites (NOx), bone alkaline phosphatase (BAP), Dickkopf
      1 (DKK-1), and osteoprotegerin (OP) were measured in 52 SpA patients who were
      treated or not with anti-TNF-alpha or NSAIDs and in 26 healthy controls using
      colourimetric and enzyme immunoassay tests. The activity and the severity of
      illness in patients with SpA were assessed using questionnaires (Bath Ankylosing
      Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index
      (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). A
      significant difference between the controls and the patients without medication
      was observed in relation to NOx, BAP, and OP (p<0.01). When the patients were
      compared with regard to their treatment, there were no clinically significant
      differences between the groups (p>0.05). In conclusion, The NOx, BAP, and OP are
      emerging as important inflammatory pathways in axial SpA. Also the anti-TNF-alpha
      or non-steroidal drugs reduce the inflammation and destructions, however these
      treatments do not modify the serum levels of these biomarkers.

PMID- 24925757
TI  - Linalool attenuates lung inflammation induced by Pasteurella multocida via
      activating Nrf-2 signaling pathway.
AB  - Pasteurellosis caused by Pasteurella multocida manifest often as respiratory
      infection in farmed small ruminants. Although the incidence of pasteurellosis due
      to P. multocida mainly takes the form of pneumonia, there is limited information
      on host factors that play a role in disease pathogenesis in the milieu of host
      pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a
      critical regulator for various inflammatory and immune responses by controlling
      oxidative stress, may play an important role in the processes of inflammation
      induced by P. multocida. In this study, linalool, a natural compound of the
      essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein
      translocation in the A549 lung cell line and in vivo. The P. multocida-induced
      pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed
      treatment with linalool decreased lung neutrophil accumulation and enhanced
      clearance of P. multocida. Furthermore, linalool significantly increased the
      expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue
      levels of several pro-inflammatory cytokines, including tumor necrosis factor
      alpha (TNF-alpha) and interleukin (IL)-6. In addition, animals treated with
      linalool had a marked improvement in survival. These findings have uncovered that
      linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in
      pathogen-mediated lung inflammation. 

PMID- 24925758
TI  - Cloning and characterization of cytoplasmic dynein intermediate chain in
      Fenneropenaeus chinensis and its essential role in white spot syndrome virus
      infection.
AB  - To investigate the role of cytoplasmic dynein in white spot syndrome virus (WSSV)
      infection, the full-length cDNA of cytoplasmic dynein intermediate chain
      (FcDYNCI) was cloned in Fenneropenaeus chinensis, which consists of 2582 bp and
      encodes a polypeptide of 660 amino acids. Sequence analysis and multiple sequence
      alignment displayed that FcDYNCI was a member of cytoplasmic dynein 1 family. The
      FcDYNCI mRNA was most highly expressed in hemocytes, which was significantly up
      regulated post WSSV infection. At 12 h post infection (hpi), confocal microscopic
      observation showed that WSSV could be co-localized with cytoplasmic dynein in
      hemocytes. After silencing by specific FcDYNCI dsRNA, the FcDYNCI mRNA level and
      the protein amount of FcDYNCI in hemocytes both exhibited a significant
      reduction, and the expression levels of three WSSV genes ie1, wsv477 and vp28 all
      exhibited the greatest decreases at 24 hpi. These results suggested that
      cytoplasmic dynein was involved in WSSV infection.

PMID- 24925759
TI  - Molecular characterization of heat shock protein 70 (HSP 70) promoter in Japanese
      flounder (Paralichthys olivaceus), and the association of Pohsp70 SNPs with heat
      resistant trait.
AB  - Ambient temperature is one of the major abiotic environmental factors determining
      the main parameters of fish vital activity. HSP70 plays an essential role in heat
      response. In this investigation, the promoter and structure of Paralichthys
      olivaceus hsp70 (Pohsp70) gene was cloned and predicted. 2558 bp upstream
      regulatory region of Pohsp70 was annotated with four potential promoter elements
      and four putative binding sites of transcription factors heat shock elements
      (HSE, nGAAn) in the upstream of the transcription start site. In addition, one
      intron with 454 bp in the 5'-noncoding region was found. Quantitative Real Time
      PCR analysis indicated that the transcript level of Pohsp70 was raised markedly
      after 1 h by heat shocked. Furthermore, 25 SNPs were identified in Pohsp70 by
      resequencing, seven of which was associated with heat resistance. In addition,
      two of the seven SNPs, namely SNP14 and SNP16, were observed in strong linkage
      disequilibrium. The haplotype with association analysis showed TAGGAG haplotype
      was more represented in heat susceptible group while (DEL/T) GAATA haplotype was
      more frequent in heat resistant group. The heat resistant SNPs and haplotype
      could be candidate markers potentially serving for selective breeding programs of
      Japanese flounder aimed at improving anti-stress and production.

PMID- 24925760
TI  - Mechanisms involved in apoptosis of carp leukocytes upon in vitro and in vivo
      immunostimulation.
AB  - During inflammation leukocyte activity must be carefully regulated, as high
      concentrations and/or prolonged action of pro-inflammatory mediators e.g.
      reactive oxygen species (ROS) can be detrimental not only for pathogens but also
      for host tissues. Programmed cell death - apoptosis is a most effective
      regulatory mechanism for down regulation of leukocyte activity, but little is
      known about this process in fish. We aimed to reveal the mechanisms of initiation
      and regulation of apoptosis in carp neutrophilic granulocytes and macrophages.
      During zymosan-induced peritonitis in carp, activated inflammatory neutrophilic
      granulocytes and monocytes/macrophages died by apoptosis. This correlated with a
      strong production of ROS, but pretreatment of the fish with NADPH oxidase
      inhibitor only slightly decreased late apoptosis. Interestingly in vitro
      incubation with zymosan or phorbol ester, but not lipopolisaccharide and poli I:C
      induced apoptosis of head kidney neutrophilic granulocytes. This coincided with
      loss of mitochondrial membrane potential. Moreover, in zymosan-stimulated
      neutrophilic granulocytes NADPH oxidase inhibitor not only reduced the production
      of ROS but also apoptosis. A similar effect was not observed in cells stimulated
      with phorbol ester, where DPI reduced ROS production, but not apoptosis. In PMA
      stimulated neutrophilic granulocytes both the respiratory burst and apoptosis
      were reduced by protein kinase inhibitor. Furthermore, a short neutrophil
      stimulation either with PMA or with zymosan did induce caspase-independent
      apoptosis. These results show that in carp, apoptosis is an important regulatory
      process during in vitro and in vivo immunostimulation. In neutrophils, protein
      kinase, but not NADPH oxidase, is involved in PMA-induced apoptosis while
      apoptosis induced by zymosan is ROS-dependent.

PMID- 24925761
TI  - Immunostimulatory effects of artificial feed supplemented with a Chinese herbal
      mixture on Oreochromis niloticus against Aeromonas hydrophila.
AB  - The effects of a Chinese herbal mixture (CHM) composed of astragalus, angelica,
      hawthorn, Licorice root and honeysuckle on immune responses and disease resistant
      of Nile tilapia (Oreochromis niloticus GIFT strain) were investigated in present
      study. Fish were fed diets containing 0 (control), 0.5%, 1.0%, 1.5% or 2.0% CHM
      (w/w) for 4 weeks. And series of immune parameters including lysozyme, cytokine
      genes TNF-alpha and IL-1beta, superoxide dismutase (SOD), peroxidase (POD),
      malondialdehyde (MDA) were measured during test period. After four weeks of
      feeding, fish were infected with Aeromonas hydrophila and mortalities were
      recorded. Results of this study showed that feeding Nile tilapia with CHM
      supplementation diet stimulated lysozyme activity, SOD activity and POD activity
      in serum, induced TNF-alpha and IL-1beta mRNA expression in head kidney and
      spleen, but decreased serum MDA content. All CHM-supplemental groups showed
      reduced mortalities following A. hydrophila infection compared with the group fed
      the control diet. These results suggested that this CHM can be applied as a
      tilapia feed supplement to elevate fish immunity and disease resistance against
      A. hydrophila.

PMID- 24925762
TI  - Dietary effect of Sargassum wightii fucoidan to enhance growth, prophenoloxidase
      gene expression of Penaeus monodon and immune resistance to Vibrio
      parahaemolyticus.
AB  - The polysaccharide fucoidan from brown seaweed Sargassum wightii was extracted
      and it was incorporated with pellet diets at three concentrations (0.1, 0.2 &
      0.3%). The fucoidan incorporated diets were fed to shrimp Penaeus monodon for 60
      days and the growth performance was assessed. The weight gain and SGR of control
      group was 6.83 g and 9.72%, respectively, but the weight gain and SGR of various
      concentrations (0.1-0.3%) of fucoidan incorporated diets fed groups of shrimp was
      increased from 7.30 to 8.20 g and 9.83 to 10.03%, respectively. After 60 days of
      feeding experiment, the relative quantification of prophenoloxidase gene of
      experimental groups over control group was analysed by RT-PCR and it was ranged
      between 2.13 and 7.95 fold increase within 33.52-34.61 threshold cycles,
      respectively at 0.1-0.3% concentrations of fucoidan. After 60 days of feeding
      experiment, the P. monodon were challenged with shrimp pathogen Vibrio
      parahaemolyticus and the mortality percentage was recorded daily up to 21 days.
      The reduction in mortality percentage of experimental groups over control group
      was recorded from 44.56 to 72.79%, respectively in 0.1-0.3% of fucoidan
      incorporated diets fed groups. During challenge experiment, all the immunological
      parameters such as THC, prophenoloxidase activity, respiratory burst activity,
      superoxide dismutase activity, phagocytic activity, bactericidal activity and
      bacterial clearance ability of experimental groups were significantly (P < 0.05)
      increased than control group. The V. parahaemolyticus load was enumerated from
      the infected shrimp at every 10 days intervals during challenge experiment. In
      control group, the Vibrio load was increased in hepatopancreas and muscle tissues
      from 10th to 21st days of challenge test. But in the experimental groups, the
      Vibrio load in both the tissues decreased positively from 10th to 21st days of
      challenge duration. It is concluded that the S. wightii fucoidan had enhanced the
      innate immunity and increased resistance to V. parahaemolyticus infection in P.
      monodon.

PMID- 24925763
TI  - Protective efficacies and immune responses induced by recombinant HCD, atpD and
      gdhA against bacterial cold-water disease in ayu (Plecoglossus altivelis).
AB  - Protective efficacies of three antigenic proteins (3-hydroxyacyl-CoA
      dehydrogenase (HCD), ATP synthase beta subunit (atpD), and glutamate
      dehydrogenase (gdhA)) against Flavobacterium psychrophilum were investigated in
      ayu (Plecoglossus altivelis). Recombinant proteins of HCD, atpD, and gdhA were
      expressed in Escherichia coli BL21 cells. Ayu were then vaccinated with
      inactivated cells via the intraperitoneal route. Compared with the empty BL21-
      and PBS-injected groups, the vaccinated group had a significantly longer survival
      time after challenge with F. psychrophilum. The antibody titers against each
      recombinant protein were significantly higher in serum from vaccinated fish,
      compared with serum from control fish. Results of indirect immunofluorescence
      assays using serum indicated that the HCD, atpD, and gdhA proteins are located on
      the surface of F. psychrophilum. These results suggest that these three surface
      proteins are protective antigens and are good candidates for development of
      vaccines against bacterial cold-water disease in ayu.

PMID- 24925764
TI  - Acetone-based cellulose solvent.
AB  - Acetone containing tetraalkylammonium chloride is found to be an efficient
      solvent for cellulose. The addition of an amount of 10 mol% (based on acetone) of
      well-soluble salt triethyloctylammonium chloride (Et3 OctN Cl) adjusts the
      solvent's properties (increases the polarity) to promote cellulose dissolution.
      Cellulose solutions in acetone/Et3 OctN Cl have the lowest viscosity reported for
      comparable aprotic solutions making it a promising system for shaping processes
      and homogeneous chemical modification of the biopolymer. Recovery of the polymer
      and recycling of the solvent components can be easily achieved. 

PMID- 24925766
TI  - L.U.St: a tool for approximated maximum likelihood supertree reconstruction.
AB  - BACKGROUND: Supertrees combine disparate, partially overlapping trees to generate
      a synthesis that provides a high level perspective that cannot be attained from
      the inspection of individual phylogenies. Supertrees can be seen as meta
      analytical tools that can be used to make inferences based on results of previous
      scientific studies. Their meta-analytical application has increased in popularity
      since it was realised that the power of statistical tests for the study of
      evolutionary trends critically depends on the use of taxon-dense phylogenies.
      Further to that, supertrees have found applications in phylogenomics where they
      are used to combine gene trees and recover species phylogenies based on genome
      scale data sets. RESULTS: Here, we present the L.U.St package, a python tool for
      approximate maximum likelihood supertree inference and illustrate its application
      using a genomic data set for the placental mammals. L.U.St allows the calculation
      of the approximate likelihood of a supertree, given a set of input trees,
      performs heuristic searches to look for the supertree of highest likelihood, and
      performs statistical tests of two or more supertrees. To this end, L.U.St
      implements a winning sites test allowing ranking of a collection of a-priori
      selected hypotheses, given as a collection of input supertree topologies. It also
      outputs a file of input-tree-wise likelihood scores that can be used as input to
      CONSEL for calculation of standard tests of two trees (e.g. Kishino-Hasegawa,
      Shimidoara-Hasegawa and Approximately Unbiased tests). CONCLUSION: This is the
      first fully parametric implementation of a supertree method, it has clearly
      understood properties, and provides several advantages over currently available
      supertree approaches. It is easy to implement and works on any platform that has
      python installed. AVAILABILITY: bitBucket page - https://afro
      juju@bitbucket.org/afro-juju/l.u.st.git. CONTACT: Davide.Pisani@bristol.ac.uk.

PMID- 24925765
TI  - Correlates of low testosterone in men with chronic spinal cord injury.
AB  - Although high rates of serum testosterone deficiency have been reported in men
      with spinal cord injury (SCI), its determinants and attributes are not yet
      established. The aim of this study was to recognize, among putative determinants
      and attributes of androgen deficiency, those significantly associated to low
      testosterone after adjustment for confounders recognizable in men with chronic
      SCI. A biochemical androgen deficiency (total testosterone <300 ng/dL) was
      exhibited by 18 of 51 patients (35.3%). Significant correlates of testosterone
      levels were as follows: weekly leisure time physical activity (LTPA) explored by
      the LTPA Questionnaire for people with SCI, body mass index (BMI), homeostatic
      model assessment of insulin resistance (HOMA-IR), triglycerides and sexual
      symptoms, explored by the aging males' symptom (AMS) questionnaire. At the
      multiple linear regression analysis, among putative determinants of low
      testosterone, only weekly LTPA and BMI exhibited a significant association with
      testosterone levels, explaining 54.2 and 9.0% of testosterone variability
      respectively. At the linear regression models, among various putative attributes
      of androgen deficiency, only lower sexual desire and, at a lesser extent, higher
      HOMA-IR, exhibited significant associations with lower testosterone levels, after
      adjustment for BMI, age, comorbidities and weekly LTPA. In conclusion, poor LTPA,
      high BMI and low sexual desire are independent predictors of low testosterone in
      men with chronic SCI. This is relevant to clinical practice, as all these
      features are routinely assessed in rehabilitation settings for SCI. As poor LTPA
      and high BMI are modifiable life-style related risk factors, prospective studies
      could clarify whether life-style modification could increase the level of
      testosterone and improve the low sexual desire, relevant clinical attribute of
      low testosterone in men with SCI. 

PMID- 24925767
TI  - Stem cell therapy for heart disease: truly beneficial?

PMID- 24925768
TI  - L-carnitine protects against testicular dysfunction caused by gamma irradiation
      in mice.
AB  - This study was conducted on mice to evaluate the radioprotective role of L
      carnitine against gamma-ray irradiation-induced testicular damage. Adult male
      mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation
      exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure
      period either in the absence and/or presence of L-carnitine at an i.p. dose of 10
      mg/kg body weight/day. Results revealed that gamma-rays irradiation suppressed
      the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine
      prior and throughout gamma-rays irradiation exposure inhibited this suppression.
      Treatment with gamma-ray irradiation or L-carnitine down-regulated expression of
      aromatase mRNA. With combined treatment, L-carnitine significantly normalized
      aromatase expression. gamma-Ray irradiation up-regulated expression of FasL and
      Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also
      showed that gamma-ray-irradiation up-regulated TNF-alpha, IL1-beta and IFN-gamma
      mRNA expressions compared to either controls or the L-carnitine treated group.
      Moreover, gamma-irradiation greatly reduced serum testosterone levels, while L
      carnitine, either alone or in combination with irradiation, significantly
      increased serum testosterone levels compared to controls. In addition, gamma
      irradiation induced high levels of sperm abnormalities (43%) which were decreased
      to 12% in the presence of L-carnitine. In parallel with these findings,
      histological examination showed that gamma-irradiation induced severe tubular
      degenerative changes, which were reduced by L-carnitine pre-treatment. These
      results clarified the immunostimulatory effects of L-carnitine and its
      radioprotective role against testicular injury.

PMID- 24925769
TI  - Retrotransposons and piRNA: the missing link in central nervous system.
AB  - From times when the whole genome were not available to the present explosion of
      genome knowledge, the biology of non-coding RNA molecules are an unknown ocean of
      gems. One among them are PIWI-interacting RNAs (piRNAs) that restrict the
      mobility of various retrotransposons. PIWI proteins and piRNAs once thought to be
      germline specific was now explored to be expressed in different somatic cells.
      Emerging proofs of piRNAs from central nervous system has raised serious
      questions regarding the role of retrotransposons and its silencing mechanism. In
      this review, we have focused on the existing knowledge of retrotransposons and
      piRNAs in the central nervous system and have provided future insights. Meta
      analysis of retrotransposons in various mammalian genomes and piRNA targets
      showcased the abundance of LINE transposon and the possibility of piRNA mediated
      retrotransposon expression. Thus, understanding the retrotransposons-piRNA
      pathway will provide a new vision for the study of development, physiology and
      pathology of the central nervous system. 

PMID- 24925770
TI  - Detection of infragenual arterial disease using non-contrast-enhanced MR
      angiography in patients with diabetes.
AB  - PURPOSE: To evaluate the diagnostic performance of a newly developed non-contrast
      enhanced MR angiography (NCE-MRA) technique using flow-sensitive dephasing (FSD)
      prepared steady-state free precession (SSFP) for detecting calf arterial disease
      in patients with diabetes. MATERIALS AND METHODS: Forty-five patients with
      diabetes who underwent routine contrast-enhanced MR angiography (CE-MRA) of lower
      extremities were recruited for NCE-MRA at the calf on a 1.5 Tesla MR system.
      Image quality evaluated on a 4-point scale and diagnostic performance for
      detecting more than 50% arterial stenosis were statistically analyzed, using CE
      MRA as the standard of reference. RESULTS: A total of 264 calf arterial segments
      were obtained in the 45 patients with 88 legs. The percentage of diagnostic
      arterial segments was all 98% for NCE- and CE-MRA. The image quality, SNR, CNR
      was 3.3, 177, 138, and 3.5, 103, 99, for NCE-MRA and CE-MRA, respectively. The
      average sensitivity, specificity, positive predictive value, negative predictive
      value, and accuracy of NCE-MRA were 97%, 96%, 90%, 99%, and 96%, respectively on
      a per-segment basis and 90%, 84%, 82%, 91%, and 87%, respectively, on a per
      patients basis. CONCLUSION: The NCE-MRA technique demonstrates adequate image
      quality in the delineation of calf arteries and consistent diagnostic performance
      for detecting significant stenosis with CE-MRA in patients with diabetes.

PMID- 24925771
TI  - Longevity and mortality of cats attending primary care veterinary practices in
      England.
AB  - Enhanced knowledge on longevity and mortality in cats should support improved
      breeding, husbandry, clinical care and disease prevention strategies. The
      VetCompass research database of primary care veterinary practice data offers an
      extensive resource of clinical health information on companion animals in the UK.
      This study aimed to characterise longevity and mortality in cats, and to identify
      important demographic risk factors for compromised longevity. Crossbred cats were
      hypothesised to live longer than purebred cats. Descriptive statistics were used
      to characterise the deceased cats. Multivariable linear regression methods
      investigated risk factor association with longevity in cats that died at or after
      5 years of age. From 118,016 cats attending 90 practices in England, 4009 cats
      with confirmed deaths were randomly selected for detailed study. Demographic
      characterisation showed that 3660 (91.7%) were crossbred, 2009 (50.7%) were
      female and 2599 (64.8%) were neutered. The most frequently attributed causes of
      mortality in cats of all ages were trauma (12.2%), renal disorder (12.1%), non
      specific illness (11.2%), neoplasia (10.8%) and mass lesion disorders (10.2%).
      Overall, the median longevity was 14.0 years (interquartile range [IQR] 9.0-17.0;
      range 0.0-26.7). Crossbred cats had a higher median longevity than purebred cats
      (median [IQR] 14.0 years [9.1-17.0] vs 12.5 years [6.1-16.4]; P <0.001), but
      individual purebred cat breeds varied substantially in longevity. In cats dying
      at or after 5 years (n = 3360), being crossbred, having a lower bodyweight, and
      being neutered and non-insured were associated with increased longevity. This
      study described longevity in cats and identified important causes of mortality
      and breed-related associations with compromised longevity. 

PMID- 24925772
TI  - Attention to Automatic Movements in Parkinson's Disease: Modified Automatic Mode
      in the Striatum.
AB  - We investigated neural correlates when attending to a movement that could be made
      automatically in healthy subjects and Parkinson's disease (PD) patients. Subjects
      practiced a visuomotor association task until they could perform it
      automatically, and then directed their attention back to the automated task.
      Functional MRI was obtained during the early-learning, automatic stage, and when
      re-attending. In controls, attention to automatic movement induced more
      activation in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate
      cortex, and rostral supplementary motor area. The motor cortex received more
      influence from the cortical motor association regions. In contrast, the pattern
      of the activity and connectivity of the striatum remained at the level of the
      automatic stage. In PD patients, attention enhanced activity in the DLPFC,
      premotor cortex, and cerebellum, but the connectivity from the putamen to the
      motor cortex decreased. Our findings demonstrate that, in controls, when a
      movement achieves the automatic stage, attention can influence the attentional
      networks and cortical motor association areas, but has no apparent effect on the
      striatum. In PD patients, attention induces a shift from the automatic mode back
      to the controlled pattern within the striatum. The shifting between controlled
      and automatic behaviors relies in part on striatal function. 

PMID- 24925777
TI  - Behavioural strategies of aggressive and non-aggressive male mice in active shock
      avoidance.
AB  - The hypothesis, partly based on findings in social interactions, that aggressive
      mice generally adopt an active behavioural strategy (cf. fight-flight) in
      threatening situations, while non-aggressive ones generally assume a passive
      strategy (cf. conservation-withdrawal) was tested using a two-way active shock
      avoidance paradigm. Overall, aggressive mice were found to be better active shock
      avoiders than non-aggressive animals; a finding that is consistent with our
      hypothesis. However, within the non-aggressive mice a clear dichotomy in high and
      low avoidance individuals was found. The high intertrial activity in the superior
      avoidance groups and the low activity in the poor avoidance group was interpreted
      as another indication of an active versus passive strategy respectively.
      Accordingly, it was concluded that not all non-aggressive mice assume a passive
      strategy, but that some mice adopt an active strategy, like all aggressive males.

PMID- 24925778
TI  - Correspondances entre la variabilite des conduites maternelles et la
      diversification des comportements de la progeniture chez la souris.
AB  - Maternal behaviour may be used as a tool for hereditary transmission of
      behavioural characters in mammals. The maternal behaviour of mice from three
      different origins which reared foster pups of the same inbred strain was
      observed. Multivariate analysis revealed differences in maternal style related
      either to genotype effects or to grandmaternal influences. The behavioural
      development of the pups was studied at days 10, 14 and 17 for neuromotor
      coordination and spontaneous activity, at day 21, 40 and 75 for locomotor
      activity and food hoarding in a semi natural environment and at day 120 of age
      for water escape learning performance. Body weights were noted at the same ages.
      Results showed both maternal effects (differences between pups reared by an
      inbred or hybrid mother) and great-grandmaternal effects (differences between
      pups reared by two reciprocal F2's). An analysis of correspondences between
      mother and pup behaviour permitted the description of a large panel of
      correlations suggesting causal relations between maternal activities and pups
      characteristics. These maternal activities may be considered primarily as agents
      of hereditary transmission. 

PMID- 24925773
TI  - Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the
      Lateral Prefrontal Cortex.
AB  - There is growing evidence that auditory selective attention operates via distinct
      facilitatory and inhibitory mechanisms enabling selective enhancement and
      suppression of sound processing, respectively. The lateral prefrontal cortex
      (LPFC) plays a crucial role in the top-down control of selective attention.
      However, whether the LPFC controls facilitatory, inhibitory, or both attentional
      mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in
      patients with LPFC damage, by comparing event-related potentials (ERPs) to
      attended and ignored sounds with ERPs to these same sounds when attention was
      equally distributed to all sounds. In control subjects, we observed 2 late
      frontally distributed ERP components: a transient facilitatory component
      occurring from 150 to 250 ms after sound onset; and an inhibitory component
      onsetting at 250 ms. Only the facilitatory component was affected in patients
      with LPFC damage: this component was absent when attending to sounds delivered in
      the ear contralateral to the lesion, with the most prominent decreases observed
      over the damaged brain regions. These findings have 2 important implications: (i)
      they provide evidence for functionally distinct facilitatory and inhibitory
      mechanisms supporting late auditory selective attention; (ii) they show that the
      LPFC is involved in the control of the facilitatory mechanisms of auditory
      attention. 

PMID- 24925779
TI  - Comparative effects of food and water deprivation on movement patterns in the
      pigeon (Columba Livia).
AB  - Groups of naive pigeons were either food or water deprived and exposed to
      response-independent fixed time schedules of reinforcement. Reinforcers were
      always appropriate to the deprivation state. After 15 Phase One sessions under
      the original deprivation state, an additional 15 Phase Two sessions were run
      under the alternate deprivation regimen. The Phase One results indicated that the
      frequency of movement over time, as measured by floorboard panels, had a
      characteristic distribution depending on deprivation state. After state-switch in
      Phase Two, both groups exhibited changes in frequency distribution over time, but
      the new distributions were different from those produced in subjects without any
      deprivation history. There appeared to be sustained effects on movement patterns
      due to prior exposure to alternate deprivation and periodic feeding regiments,
      results which confirm earlier experimental work. The findings are discussed in
      light of research on the effect of prior response-independent schedule training,
      the matching law, and the effects of contextual conditioning. 

PMID- 24925780
TI  - Intradimensional and extradimensional shifts in conditional discrimination.
AB  - Two groups of pigeons learned a two key conditional discrimination. Color was the
      conditional stimulus and form the choice stimulus for subjects in one group. Form
      was the conditional stimulus and color the choice stimulus in the other group.
      Half the subjects in each group then underwent an intradimensional shift: The
      conditional stimulus dimension and choice stimulus dimension were unchanged but
      the correct and incorrect stimulus compounds were reversed. The remaining
      subjects underwent an extra-dimensional shift in which the conditional stimulus
      dimension and choice stimulus dimension were reversed. Subjects which experienced
      an intradimensional shift learned the new conditional discrimination more
      quickly. It was concluded that subjects followed rules to solve conditional
      discriminations but also learned the functions of each stimulus dimension. 

PMID- 24925781
TI  - Extraction of melodies in behavioural sequences.
AB  - A method is proposed that extracts a set of phrases, or "melodies", from a
      behavioural sequence, using a technique for extracting and compressing chains
      based on Information Theory. These melodies are validated by reference to a
      statistical criterion. An application of this method to the analysis of the
      behavioural sequences of two groups of mice, the first observed during the day,
      the second during the night, is described. The advantages and the limitations of
      the method are discussed. 

PMID- 24925782
TI  - Intermittent stimulation and delay of puberty by urinary chemosignals and social
      contact in wild stock female house mice (Mus Domesticus).
AB  - A sequence of six experiments using wild stock house mouse (Mus domesticus)
      tested the effects of intermittent stimulation with either the urinary
      chemosignal released by grouped female mice or social contact from grouped
      females on the age of first vaginal oestrus in young females. Weanling female
      mice were exposed to bedding soiled by grouped females or cages containing
      grouped females for 15 min periods, then removed for a prescribed period, and
      placed again in a cage with soiled bedding or grouped females. The nature of the
      exposure to the puberty delaying effect, the number of total exposures each day,
      the total length of exposure to the stimulus, and the total time period over
      which the exposures occurred were varied. None of the treatment regimes employed
      here with soiled bedding from grouped females resulted in delays in the onset of
      first oestrus in test females. Young females exposed to grouped females for 6 or
      8 exposures in a 4 h period, 6 or 8 exposures in an 8 h period, or 8 exposures in
      a 12 h period were significantly delayed in attaining puberty relative to control
      females that were exposed to cages containing clean bedding. These results are in
      contrast to earlier findings involving chemosignals that accelerate first oestrus
      wherein young females exhibited the capacity to accumulate the exposures to the
      urinary chemosignals from males, females in oestrus and pregnant or lactating
      females. Direct exposure to the grouped females on an intermittent basis can
      provide stimulation that is cummulative and results in delays in the onset of
      first oestrus. 

PMID- 24925783
TI  - Lack of spontaneous alternation in favor of perseveration in domestic fowls and
      pigeons.
AB  - When allowed successive free choices of the arms of a T-maze, domestic fowls and
      pigeons repeated rather than alternated entries of the two alternatives. Such
      perseveration was less when one arm was black and the other white than when both
      were grey. Perseveration increased between the beginning and the end of the
      experiment and was unaffected by confinement to a chosen arm for 30 or 60
      seconds. Removal from a chosen arm may have provided relief from an aversive
      situation and thus reinforced subsequent re-entries of the same arm. The results
      were therefore accounted for by the adoption of a win-stay escape strategy. 

PMID- 24925784
TI  - Comportements maternels chez la souris: Telle mere telle fille?
AB  - Relations between mother' and daughter' maternal behaviour were surched by
      continuous recording of locomotor activity and time spent in the nest during the
      first six days postpartum in two isogenic generations of mice. The first
      generation was composed of either heterozygous Fl or inbred C57BL/6 (=B6) dams,
      both giving birth after ovarian graft to B6 pups. In each litter the maternal
      behaviour of a female was studied in the same conditions as for her mother. Even
      in developing in quite different environments, both groups of B6 daughters did
      not differ for the behavioural patterns under study. Links between mother' and
      daughter' activity during the nursing period were shown in one group by important
      negative correlations suggesting a feedbak regulation mechanism. This illustrate
      a possible way of passive hereditary transmission of acquired behavioural
      characteristics. 

PMID- 24925785
TI  - Immobility reactions in socially behaving rabbits: Relation to hippocampal
      electrical activity.
AB  - The presence of an intruder conspecific of the same sex caused a series of
      conflict reactions in rabbits living in a semi-natural environment. In some
      animals, defensive responses were predominant and two immobility reactions were
      observed. One consisted of freezing when the intruder was exploring at a
      distance; the other consisted of subdued posture in close contact with the
      intruder. Hippocampal EEG, recorded by telemetry, showed two different profiles.
      During freezing, rhythmic slow activity prevailed and during subdued posture an
      irregular pattern was predominant. Frequency increased when the intruder was in
      close contact with the resident. Aspects such as distance or behaviour of the
      intruder were found to affect both behavioural strategies and hippocampal
      electrical responses. 

PMID- 24925786
TI  - The causal and functional organization of mating behaviour in Gammarus pulex
      (Amphipoda).
AB  - The causal and functional organization of mating behaviour in male Gammarus pulex
      was investigated using Principal Components Analysis. Males were presented with
      1) unmoulted novel females and 2) moulted females ready for insemination.
      Composite measures of behaviour were derived from an array of often correlated
      behavioural measures and activities. Three factors describe Precopulatory
      behaviour and are labelled according to the activities which define them as;
      "decisiveness", "courtship" and "tenacity". Three factors describe Copulatory
      behaviour; "decisiveness", "preparation" and "copulation". These factors reflect
      the internal organization of male behaviour and motivational state. In addition,
      they allow for investigation of the functional significance of behaviour.
      Correlation analysis showed clear relationships between Precopula behaviour and
      female reproductive quality. As the time from moult of offered females decreased,
      males became more "decisive" in their actions and were more "tenacious" towards
      females, whereas the "courtship" component remained constant. No aspect of
      Copulatory behaviour was influenced by the absolute or relative size of
      copulating animals. These results are discussed with reference to activities
      displayed by other Gammarus spp. and compared with other studies that employ
      factor analyses. 

PMID- 24925787
TI  - Effect of type of opponent on aggression in male mice with particular reference
      to studies with antihormones.
AB  - The potential influence of the type of opponent used in intermale aggression
      encounters to assess the actions of drugs was examined. Two experiments were
      carried out, one with the antiandrogen Cyproterone Acetate and the other with the
      antioestrogen CI-680 (both administered every three days over 25 days). In both
      experiments the antihormone-treated subjects encountered different opponents,
      namely: a) an antihormone-treated male, b) a non aggressive anosmic male or c) a
      vehicle-treated male. Vehicle-treated subjects also confronted a vehicle-treated
      or an anosmic opponent. The behaviour displayed by antihormone-treated subjects
      varied according to the characteristics of the partner, suggesting that the
      effects of drugs might be interpreted differently depending on the type of animal
      employed as an adversary. In fact, some of the apparently contradictory results
      reported in the literature seem to be consequences of the utilisation of
      different kinds of opponents. It is concluded that the choice of the opponent is
      of paramount importance in the study of drug actions on intermale aggression
      tests and that using more than one type of opponent can provide more complete
      information about the actions of particular drugs. 

PMID- 24925788
TI  - Experience of defeat increases the susceptibility to catatonic - like state in
      mice.
AB  - The ability to develop the catatonic-like state (reflex immobility reaction -
      RIR) due to stimulation of the skin at the scruff was investigated in mice of two
      strains - C57BL/6J and CBA/Lac. The total time of immobility and number of
      paroxysms during test were measured. It has been shown that the number of
      paroxysms was significantly fewer and the total time of immobility was
      significantly longer in CBA/Lac strain than in C57BL/6J. In each strain group
      housed animals as well as submissive ones with successive experience of defeats
      demonstrated a more expressed immobility than individually housed or aggressive
      males with successive experience of victories, respectively. Changing the social
      status in aggressive animals as a consequence of confrontation with aggressive
      males resulted in the increased immobility in CBA/Lac but not in C57BL/6J mice.
      The results suggest that the experience of defeat in submissive males is
      connected with increased ability to develop RIR. 

PMID- 24925789
TI  - Constraints on the process of interresponse-time reinforcement as the explanation
      of variable-interval performance.
AB  - Computer modelling was used to investigate the adequacy of the principle of
      reinforcement of single interresponse-times (IRTs) as an explanation of variable
      interval performance. Variations in three components of models employing IRT
      reinforcement were simulated; these were (i) rules for selecting previously
      reinforced IRTs from the IRT memory as "candidates" for output (acceptance
      rules), (ii) processes involving the transformation of previously-reinforced IRTs
      to generate behavioural variability, and (iii) the role of the minimum IRT value
      permitted by the models. In general, simulation output resembled experimental
      data only when (i) acceptance rules discriminated strongly against long, and in
      favour of short, IRTs; and (ii) when IRTs were transformed by distributions in
      which standard deviation was a large fraction (50-125%) of the mean, thus
      generating substantial IRT variability. Simulation results were analyzed by means
      of Herrnstein's hyperbolic equation, and in general, it was found that the output
      of IRT reinforcement models was insensitive to the rate of reinforcement
      received, as well as conforming less well to Herrnstein's equation than did
      experimental data. Overall, therefore, it was concluded that models of the
      reinforcement of single IRTs could provide an adequate simulation of VI
      performance only when the processes within them operated within narrow
      constraints. Even then, models involving the reinforcement of single IRTs could
      adequately simulate only those VI data in which response rate was insensitive to
      reinforcement rate. 

PMID- 24925790
TI  - Schedules of reinforcement as regulators of dispersion patterns.
AB  - An eight-rat eight-station operant conditioning arena was used to study the
      spatial structure and temporal stability of foraging dispersion patterns. Food
      was obtained by bar pressing as the population was exposed to an ascending series
      of the fixed and variable aspects of ratio and interval schedules of
      reinforcement. Dispersion patterns, defined by the number of rats simultaneously
      foraging at each of the eight stations, and the temporal changes in these
      patterns, were the dependent variables. Both variables exhibited a unique
      relationship to each schedule type and value. The absence of such relationships
      when either food supply or response costs were examined suggests that these
      factors were not the determinants of spatio-temporal structure. An account is
      provided of how schedules may interact with behavioral foraging chains to explain
      dispersion patterns. 

PMID- 24925791
TI  - Response selection in operant learning.
AB  - We show that simple, contiguity-based, nonassociative response-selection process
      provides a qualitative account for both anomalous and nonanomalous properties of
      operant conditioning. The process can easily be extended to permit associative
      effects; it may therefore represent the initial processing stage for all
      conditioning in higher vertebrates. 

PMID- 24925792
TI  - Feeding and emigration of the ant Tapinoma erraticum (Formicidae Dolichoderinae).
      Experimental analysis of the use of space.
AB  - Visits to feeding sites and potential nesting sites by several colonies of
      Tapinoma erraticum was studied in the laboratory. During the feeding phase ant
      use of space was significantly asymmetrical (different visit frequencies to
      identical sites) and reflects environmental structuring. Such asymmetrical
      patterns of space use may have influenced subsequent orientation of nest search
      and nest site selection after experimental disturbance. When the colony was
      disturbed, i.e when the water source and the opaque nest cover were removed
      activity remained mainly diurnal. There was relative increase in frequency of
      visits to the subsequently chosen nesting site as compared with visits to feeding
      sites. Selected nests could be in a zone visited frequently before disturbance,
      for example close to a feeding source, but other parameters must be considered to
      account for colony choice. The question of a collective decision making is
      discussed. 

PMID- 24925793
TI  - [Duplex ultrasound detection of type II endoleaks after endovascular aneurysm
      repair: Interest of contrast enhancement. Another point of view].

PMID- 24925794
TI  - [Imaging of pulmonary artery involvement in Takayasu disease].
AB  - OBJECTIVES: Illustrate imaging aspects of pulmonary artery involvement in
      Takayasu's arteritis. PATIENTS AND METHODS: Retrospective study of six patients
      among 28 patients with Takayasu arteritis whose disease involved the pulmonary
      arteries and to review their clinical and computed tomography data. RESULTS: Mean
      patient age among those with pulmonary artery involvement was 34 years. All
      patients exhibited extensive lesions of systemic arteries. The most common
      computed tomography angiography sign was wall thickening. Dilatation of the
      pulmonary artery trunk was observed in one-third of cases. CONCLUSION: Pulmonary
      arterial involvement in Takayasu's disease is not uncommon. Computed tomography
      is a reliable imaging technique to establish the diagnosis.

PMID- 24925795
TI  - Metabolic syndrome and sex-specific socio-economic disparities in childhood and
      adulthood: the Korea National Health and Nutrition Examination Surveys.
AB  - AIMS: To examine whether adulthood and/or childhood sex-specific socio-economic
      disparities are associated with metabolic syndrome and its components in a
      developed non-Western setting. METHODS: Based on the Fourth Korea National Health
      and Nutrition Examination Surveys, 14 888 people aged >= 20 years were analysed
      to evaluate the effect of adult and childhood socio-economic status on metabolic
      syndrome. Metabolic syndrome was defined according to the National Cholesterol
      Education Program Adult Treatment Panel III guidelines. Logistic regression
      analyses were conducted to calculate the odds ratios for metabolic syndrome and
      each component of metabolic syndrome in later life. RESULTS: The age-standardized
      prevalence of metabolic syndrome was 26.6% for men and 21.3% for women. Compared
      with the highest level of education, men with the lowest education level were
      significantly less likely to have metabolic syndrome (odds ratio 0.76, 95% CI
      0.60-0.96), whereas the opposite association was found in women (odds ratio 3.29,
      95% CI 2.45-4.42). Men who were manual labourers and economically inactive had a
      lower prevalence of metabolic syndrome compared with those with non-manual jobs
      (odds ratio 0.82, 95% CI 0.69-0.98 and odds ratio 0.79, 95% CI 0.64-0.99,
      respectively), but the reverse association was observed in women (odds ratio
      1.34, 95% CI 1.04-1.73 and odds ratio 1.40, 95% CI 1.09-1.81, respectively). A
      significant interaction between combined adulthood and childhood socio-economic
      status on the presence of metabolic syndrome was observed (P < 0.05).
      CONCLUSIONS: Our findings suggest that sex-specific socio-economic disparities in
      childhood and adulthood have differential effects on the prevalence of metabolic
      syndrome and its individual components in Korea.

PMID- 24925796
TI  - Libman-sacks endocarditis exclusively involving the tricuspid valve in a patient
      with systemic lupus erythematosus.
AB  - Libman-Sacks endocarditis, characterized by sterile verrucous vegetations, is a
      rare but typical cardiac manifestation of systemic lupus erythematosus. It
      primarily leads to lesions of the mitral and aortic valves, but isolated
      tricuspid valve involvement is exceptional. We report the case of a 40-year-old
      woman with large tricuspid valve vegetations, thickening, and regurgitation.
      Clinical findings and laboratory tests confirmed the diagnosis of systemic lupus
      erythematosus. The patient successfully recovered following tricuspid valve
      replacement. Echocardiography is the definitive imaging modality for assessing
      cardiac valvular involvement, choosing appropriate therapy, and evaluating the
      prognosis of Libman-Sacks endocarditis in systemic lupus erythematosus. (c) 2014
      Wiley Periodicals, Inc. J Clin Ultrasound 43:265-267, 2015.

PMID- 24925797
TI  - Activation of the developmental pathway neurogenin-3/microRNA-7a regulates
      cholangiocyte proliferation in response to injury.
AB  - The activation of the biliary stem-cell signaling pathway hairy and enhancer of
      split 1/pancreatic duodenal homeobox-1 (Hes-1/PDX-1) in mature cholangiocytes
      determines cell proliferation. Neurogenin-3 (Ngn-3) is required for pancreas
      development and ductal cell neogenesis. PDX-1-dependent activation of Ngn-3
      initiates the differentiation program by inducing microRNA (miR)-7 expression.
      Here we investigated the role Ngn-3 on cholangiocyte proliferation. Expression
      levels of Ngn-3 and miR-7 isoforms were tested in cholangiocytes from normal and
      cholestatic human livers. Ngn-3 was knocked-down in vitro in normal rat
      cholangiocytes by short interfering RNA (siRNA). In vivo, wild-type and Ngn-3
      heterozygous (+/-) mice were subjected to 3,5-diethoxycarbonyl-1,4
      dihydrocollidine (DDC) feeding (a model of sclerosing cholangitis) or bile duct
      ligation (BDL). In the liver, Ngn-3 is expressed specifically in cholangiocytes
      of primary sclerosing cholangitis (PSC) patients and in mice subjected to DDC or
      BDL, but not in normal human and mouse livers. Expression of miR-7a-1 and miR-7a
      2 isoforms, but not miR-7b, was increased in DDC cholangiocytes compared to
      normal ones. In normal rat cholangiocytes, siRNA against Ngn-3 blocked the
      proliferation stimulated by exendin-4. In addition, Ngn-3 knockdown neutralized
      the overexpression of insulin growth factor-1 (IGF1; promitotic effector)
      observed after exposure to exendin-4, but not that of PDX-1 or VEGF-A/C.
      Oligonucleotides anti-miR-7 inhibited the exendin-4-induced proliferation in
      normal rat cholangiocytes, but did not affect Ngn-3 synthesis. Biliary
      hyperplasia and collagen deposition induced by DDC or BDL were significantly
      reduced in Ngn-3(+/-) mice compared to wild-type. CONCLUSION: Ngn-3-dependent
      activation of miR-7a is a determinant of cholangiocyte proliferation. These
      findings indicate that the reacquisition of a molecular profile typical of organ
      development is essential for the biological response to injury by mature
      cholangiocytes.

PMID- 24925799
TI  - Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement
      therapy in patients with primary immunodeficiency disorders.
AB  - Human immunoglobulin is an established replacement therapy for patients with
      primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase
      (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin
      interstitium enabling large volumes of fluid or drug solutions to be infused and
      absorbed subcutaneously. HyQvia(r) (IGHy) is a new combination product whereby
      rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused
      through the same needle. Thus, IGHy can be administered at a reduced frequency
      compared with non-facilitated subcutaneous injection of human immunoglobulin, and
      with a lower frequency of infusion reactions than with intravenous
      administration. Home-based administration of IGHy is also feasible for adequately
      trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in
      a non-randomized, open-label, phase 3 study in patients aged >=2 years with PIDs
      who were receiving human immunoglobulin replacement therapy (n = 87). In this
      study, trough IgG concentrations, acute serious bacterial infection rates
      (primary endpoint) and occurrences of adverse events during the IGHy treatment
      period were generally similar to those observed during an intravenous treatment
      period. IGHy was associated with a numerically lower rate of systemic adverse
      events and a numerically higher rate of localized adverse events than those
      observed with intravenous treatment. Compared with intravenous administration,
      IGHy was administered at a significantly higher maximum flow rate and at a
      similar frequency. Most patients preferred IGHy over intravenous administration.
      IGHy offers a new method for subcutaneous delivery of human immunoglobulin
      replacement therapy in patients with PIDs.

PMID- 24925798
TI  - A comprehensive obstetric patient safety program reduces liability claims and
      payments.
AB  - Begun in 2003, the Yale-New Haven Hospital comprehensive obstetric safety program
      consisted of measures to standardize care, improve teamwork and communication,
      and optimize oversight and quality review. Prior publications have demonstrated
      improvements in adverse outcomes and safety culture associated with this program.
      In this analysis, we aimed to assess the impact of this program on liability
      claims and payments at a single institution. We reviewed liability claims at a
      single, tertiary-care, teaching hospital for two 5-year periods (1998-2002 and
      2003-2007), before and after implementing the safety program. Connecticut statute
      of limitations for professional malpractice is 36 months from injury.
      Claims/events were classified by event-year and payments were adjusted for
      inflation. We analyzed data for trends as well as differences between periods
      before and after implementation. Forty-four claims were filed during the 10-year
      study period. Annual cases per 1000 deliveries decreased significantly over the
      study period (P < .01). Claims (30 vs 14) and payments ($50.7 million vs $2.9
      million) decreased in the 5-years after program inception. Compared with before
      program inception, median annual claims dropped from 1.31 to 0.64 (P = .02), and
      median annual payments per 1000 deliveries decreased from $1,141,638 to $63,470
      (P < .01). Even estimating the monetary awards for the 2 remaining open cases
      using the median payments for the surrounding 5 years, a reduction in the median
      monetary amount per case resulting in payment to the claimant was also
      statistically significant ($632,262 vs $216,815, P = .046). In contrast, the
      Connecticut insurance market experienced a stable number of claims and markedly
      increased cost per claim during the same period. We conclude that an obstetric
      safety initiative can improve liability claims exposure and reduce liability
      payments.

PMID- 24925800
TI  - Diffusion-tensor MRI and tractography of the esophageal wall ex vivo.
AB  - PURPOSE: To demonstrate the feasibility of diffusion-tensor magnetic resonance
      imaging (MRI) and tractography as a means of evaluating the individual layers of
      the normal esophageal wall by using esophageal specimens containing carcinoma.
      MATERIALS AND METHODS: Twelve esophageal specimens each containing a carcinoma
      that were preserved in formalin were studied with a 7.0-T small-bore MR system
      equipped with a four-channel phased-array surface coil. Diffusion-tensor MR
      images were obtained with a field of view of 50-60 * 25-30 mm, matrix of 256 *
      128, section thickness of 1 mm, b value of 1000 sec/mm(2) , and motion-probing
      gradient in seven noncollinear directions. The diffusion-weighted images,
      apparent diffusion coefficient (ADC) maps, fractional anisotropy (FA) maps,
      direction-encoded color FA maps, and tractographic images in the 12 esophageal
      specimens were compared with the histopathologic findings, which served as the
      gold standard. RESULTS: The diffusion-weighted images, ADC maps, FA maps, and
      direction-encoded color FA maps depicted the normal esophageal wall in all 12
      specimens (100%) as consisting of eight layers, which clearly corresponded to the
      tissue layers of the esophageal wall. The ADC, FA, lambda1 , lambda2 , and
      lambda3 values of each layer of the normal esophageal wall were significantly
      different from the corresponding values of the adjacent layer or layers of the
      esophageal wall. Diffusion-tensor tractographic images were able to selectively
      display the layers of the normal esophageal wall. CONCLUSION: By looking at the
      normal part of esophageal specimens containing carcinoma, we have demonstrated
      that diffusion-tensor MRI and tractography are capable of depicting the
      individual tissue layers of the normal esophageal wall.

PMID- 24925802
TI  - Effect of left ventricular assist device implantation and heart transplantation
      on habitual physical activity and quality of life.
AB  - The present study defined the short- and long-term effects of left ventricular
      assist device (LVAD) implantation and heart transplantation (HT) on physical
      activity and quality of life (QoL). Forty patients (LVAD, n = 14; HT, n = 12; and
      heart failure [HF], n = 14) and 14 matched healthy subjects were assessed for
      physical activity, energy expenditure, and QoL. The LVAD and HT groups were
      assessed postoperatively at 4 to 6 weeks (baseline) and 3, 6, and 12 months. At
      baseline, LVAD, HT, and HF patients demonstrated low physical activity, reaching
      only 15%, 28%, and 51% of that of healthy subjects (1,603 +/- 302 vs 3,036 +/-
      439 vs 5,490 +/- 1,058 vs 10,756 +/- 568 steps/day, respectively, p <0.01). This
      was associated with reduced energy expenditure and increased sedentary time (p
      <0.01). Baseline QoL was not different among LVAD, HT, and HF groups (p = 0.44).
      LVAD implantation and HT significantly increased daily physical activity by 60%
      and 52%, respectively, from baseline to 3 months (p <0.05), but the level of
      activity remained unchanged at 3, 6, and 12 months. The QoL improved from
      baseline to 3 months in LVAD implantation and HT groups (p <0.01) but remained
      unchanged afterward. At any time point, HT demonstrated higher activity level
      than LVAD implantation (p <0.05), and this was associated with better QoL. In
      contrast, physical activity and QoL decreased at 12 months in patients with HF (p
      <0.05). In conclusion, patients in LVAD and HT patients demonstrate improved
      physical activity and QoL within the first 3 months after surgery, but physical
      activity and QoL remain unchanged afterward and well below that of healthy
      subjects. Strategies targeting low levels of physical activity should now be
      explored to improve recovery of these patients. 

PMID- 24925803
TI  - Transradial percutaneous coronary interventions in acute coronary syndrome.
AB  - Transradial access (TRA) is becoming increasingly used worldwide for percutaneous
      coronary intervention (PCI) after acute coronary syndromes (ACS). TRA compared
      with transfemoral access has been noted to improve clinical outcomes in clinical
      trials and large registry cohort studies. However, much of the benefits of TRA
      PCI are noted in patients with ST elevation myocardial infarction (STEMI)
      undergoing primary PCI, where TRA PCI has been associated with reductions in
      major bleeding events and potentially lower short- and long-term mortality rates.
      Although much less data exist for TRA PCI in unstable angina and/or non-ST
      elevation myocardial infarction, similar reductions in bleeding and mortality
      have not been consistently described. Differences in outcome benefit with TRA PCI
      among various ACS subtypes may be attributable to the potentially increased
      inherent risk of periprocedural bleeding in STEMI compared with unstable angina
      and/or non-ST elevation myocardial infarction. Pre- and intra-procedural factors
      associated with STEMI treatment, such as use of pharmacoinvasive therapy and
      aggressive antithrombotic regimens likely increase bleeding risk in patients. In
      conclusion, this review describes the evidence for TRA PCI across the spectrum of
      ACS and highlights why differences in clinical benefit may exist among ACS
      subtypes. 

PMID- 24925801
TI  - Anticoagulant and antiplatelet therapy in patients with atrial fibrillation
      undergoing percutaneous coronary intervention.
AB  - The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in
      addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial
      fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not
      yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome
      Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were
      identified among 12,716 patients undergoing first PCI. Cumulative 5-year
      incidence of stroke was higher in patients with AF than in no-AF patients (12.8%
      vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score >=2 (75.2%),
      only 506 patients (47.9%) received OAC with warfarin at hospital discharge.
      Cumulative 5-year incidence of stroke in the OAC group was not different from
      that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range
      (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and
      only 154 of 409 patients (37.7%) with international normalized ratio data had TTR
      >=65%. Cumulative 5-year incidence of stroke in patients with TTR >=65% was
      markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In
      a 4-month landmark analysis in the OAC group, there was a trend for higher
      cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than
      in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p =
      0.10, respectively). In conclusion, OAC was underused and its intensity was
      mostly suboptimal in real-world patients with AF undergoing PCI, which lead to
      inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not
      reduce stroke incidence. 

PMID- 24925804
TI  - Reply to: Gray et al.

PMID- 24925805
TI  - Optimization of a whole blood phenotyping assay for enumeration of peripheral
      blood leukocyte populations in multicenter clinical trials.
AB  - Vaccination with viral vectors or adjuvants can induce early changes in
      circulating peripheral blood leukocytes that are predictive of a protective
      immune response. In this study, we define an 11-color whole blood antibody
      staining Trucount Panel (TP1) to enumerate and phenotype the major leukocyte
      populations in a human vaccine experimental medicine trial setting. TP1 can be
      prepared up to 8weeks prior to use, enabling bulk preparation at a central
      laboratory and distribution to clinical sites. Cells in whole blood must be
      stained within 4h of draw to accurately detect the major cell populations.
      Staining of cells with TP1 followed by storage and shipping at -80 degrees C to a
      central laboratory has little to no effect on the cell concentrations observed.
      We also present data from an HIV vaccine multicenter clinical trial obtained
      using the optimized TP1 assay protocol and show that the data produced accurately
      correlates with complete blood count (CBC) data. Taken together, these data
      indicate the optimized TP1 panel assay can be used in a multicenter clinical
      trial setting to increase our understanding of systemic responses to vaccination
      or disease. 

PMID- 24925806
TI  - Applying caspase-1 inhibitors for inflammasome assays in human whole blood.
AB  - Caspase-1 processes pro-IL-1beta and pro-IL-18 into bioactive forms. Caspase-1
      activity is regulated by a multiprotein complex known as an inflammasome.
      Multiple danger and damage associated signals drive inflammasome formation.
      Currently, evaluation of inflammasome activity is of particular interest as its
      role in chronic and acute inflammatory pathologies becomes evident. Specific
      inhibitors are therefore required to evaluate the contributions of the
      inflammasome and IL-1beta to these disease processes. While several inhibitors
      are available for caspase-1 blocking experiments, in this study we show effects
      of two commonly used caspase inhibitors: z-VAD-fmk and ac-YVAD-cmk on secretion
      of pro-inflammatory cytokines: IL-1beta, TNFalpha, IL-8 and IL-6 in whole blood
      stimulated with LPS. We demonstrate ac-YVAD-cmk is a specific caspase-1 inhibitor
      resulting in pronounced decreases in IL-1beta and less suppression of TNFalpha,
      IL-6 and IL-8, while pan-caspase inhibitor, z-VAD-fmk, only weakly suppressed Il
      1beta while acting strongly on the other three cytokines. Furthermore, we
      demonstrated that simultaneous treatment of whole blood cultures with inhibitor
      and LPS fails to attenuate the IL-1beta response. In contrast, pretreatment with
      inhibitors prior to LPS stimulation is required to achieve marked decreases in IL
      1beta production. Thereby also demonstrating IL-1beta release by cells in whole
      blood culture stimulated with LPS is a rapid response. Thus studying
      inflammasome/caspase-1/IL-1beta axis requires appropriate selection and
      application of inhibitors. 

PMID- 24925807
TI  - A rapid ELISA-based method for screening Bordetella pertussis strain production
      of antigens included in current acellular pertussis vaccines.
AB  - INTRODUCTION: Despite extensive vaccinations, there have been pertussis epidemics
      in many countries including the Netherlands, the UK, Australia and the USA.
      During these epidemics Bordetella pertussis strains not producing the vaccine
      antigen pertactin (Prn) are emerging and increasing in numbers. However, methods
      for confirming PRN production of B. pertussis isolates are combined PCR or PCR
      based sequencing tests and western blotting. Furthermore, data about production
      of pertussis toxin (PT) and filamentous hemagglutinin (FHA) of these isolates are
      scarce. Fimbriae (Fim) production is usually determined by agglutination and
      reported as serotype. In this study we developed an easy, accurate and rapid
      method for screening PT and FHA production. Methods for Prn and Fim production
      have been published earlier. METHODS: We analyzed altogether 109 B. pertussis
      strains, including 103 Finnish B. pertussis strains collected during 2006-2013,
      international strain Tohama I, French strains FR3496 (PT-negative), FR3693 (Prn
      negative) and FR4624 (FHA-negative) and Fim-serotype reference strains S1
      (producing only Fim2) and S3 (producing only Fim3). An indirect ELISA with whole
      bacterial cells as coating antigen was developed and used for rapid screening of
      the B. pertussis strains. Production of different antigens (PT, FHA, Prn, Fim2
      and Fim3) was detected with specific monoclonal antibodies (mAbs). RESULTS: From
      the 103 Finnish B. pertussis strains tested, all were positive for PT, FHA and
      Fim. Four were found negative for Prn, and they were isolated during 2011-2013.
      CONCLUSIONS: The newly developed method proved to be useful and simple for rapid
      screening of different antigen production of B. pertussis isolates.

PMID- 24925808
TI  - A highly relevant and efficient single step method for simultaneous depletion and
      isolation of human regulatory T cells in a clinical setting.
AB  - Regulatory T cells (Tregs) are pivotal in preventing autoimmunity. They play a
      major but still ambiguous role in cancer and viral infections. Functional studies
      of human Tregs are often hampered by numerous technical difficulties arising from
      imperfections in isolating and depleting protocols, together with the usual low
      cell number available from clinical samples. We standardized a simple procedure
      (Single Step Method, SSM), based on magnetic beads technology, in which both
      depletion and isolation of human Tregs with high purities are simultaneously
      achieved. SSM is suitable when using low cell numbers either fresh or frozen from
      both patients and healthy individuals. It allows simultaneous Tregs isolation and
      depletion that can be used for further functional work to monitor suppressive
      function of isolated Tregs (in vitro suppression assay) and also effector IFN
      gamma responses of Tregs-depleted cell fraction (OX40 assay). To our knowledge,
      there is no accurate standardized method for Tregs isolation and depletion in a
      clinical context. SSM could thus be used and easily standardized across different
      laboratories. 

PMID- 24925810
TI  - Nutrition and the brain: what advice should we give?
AB  - The knowledge base of nutrition and the brain is steadily expanding. Much of the
      research is aimed at ways to protect the brain from damage. In adults, the major
      causes of brain damage are aging and dementia. The most prominent dementia, and
      the condition that grabs the most public attention, is Alzheimer's disease. The
      assumption in the field is that possibly some change in nutrition could protect
      the brain and prevent, delay, or minimize Alzheimer's disease damage. Presented
      here is a framework for understanding the implications of this research. There is
      a gap between publishing research results and change in public nutrition
      behavior. Several influencing elements intervene. These include regulatory
      agencies and all the organizations and people who advise the public, all with
      their own perspectives. In considering what advice to give, advisors may consider
      effectiveness, research model, persuasiveness, and risks, among other factors.
      Advice about nutrition and Alzheimer's disease today requires several caveats. 

PMID- 24925811
TI  - Choriocapillaris breakdown precedes retinal degeneration in age-related macular
      degeneration.
AB  - This work presents a combined light and electron microscopical approach to
      investigate the initial breakdown of the retinal pigment epithelium (RPE) and
      choriocapillaris (CC) in age-related macular degeneration (AMD). Perimacular
      sections of 12 dry and wet AMD eyes (82 +/- 15 years) and 7 age-matched controls
      (75 +/- 10 years) without retinal pathology were investigated. Disease
      progression was classified into 5 stages of retinal degeneration to investigate
      the concurrent CC breakdown. Special emphasis was laid on transitions where
      intact CC-RPE-retina complexes went over into highly atrophied areas. AMD
      sections showed elevated loss of photoreceptors, RPE and CC (p < 0.01), and
      thickened Bruch's membrane with increased basal laminar and linear deposits
      compared with controls. Up to 27% of the CC was lost in controls although RPE and
      retina were still intact. This primary loss of CC further increased with AMD (up
      to 100%). The data implicate that CC breakdown already occurs during normal aging
      and precedes degeneration of the RPE and retina with AMD, defining AMD as a
      vascular disease. Particular attention should be given to the investigation of
      early AMD stages and transitional stages to the late stage that reveal a possible
      sequence of degenerative steps with aging and AMD.

PMID- 24925812
TI  - Territoriality and reproductive behaviour in the goldsinny, Ctenolabrus rupestris
      L.
AB  - Territoriality and reproductive behaviour of the Goldsinny, Ctenolabrus
      rupestris, was studied in the waters around Tjarno on the Swedish west coast.
      Observations were made by SCUBA-diving and from an observation raft and in
      aquaria. Patrolling, foraging, courtship and aggression were defined and
      quantified throughout the reproductive season and after. Spawning activity was
      also examined and it has been found that one male spawns with several females.
      During spawning accesory males may be present at fertilisation and their role is
      discussed. Both sinking and floating eggs were recorded, which are discussed.
      After spawning some females became territorial as well as some subadults. The
      territories showed a consistency according to their boundaries and occupants from
      year to year. 

PMID- 24925809
TI  - Management of Italian patients with advanced non-small-cell lung cancer after
      second-line treatment: results of the longitudinal phase of the LIFE
      observational study.
AB  - INTRODUCTION/BACKGROUND: Patients with advanced NSCLC who experience disease
      progression after second-line therapy might receive further active treatment.
      LIFE was an Italian cohort multicenter observational study composed of a cross
      sectional and a longitudinal phase. PATIENTS AND METHODS: In the longitudinal
      phase, described here, the primary aim was to determine the proportion of
      patients receiving third-line therapy among those who received second-line active
      treatment according to clinical practice. The proportion of patients receiving
      further treatment lines was also estimated. RESULTS: The longitudinal phase was
      conducted between January and August 2012. Of 464 patients who began second-line
      therapy outside of clinical trials within the baseline evaluation, 56 (12.1%)
      were still receiving second-line therapy at the end of the observation period and
      17 (3.7%) withdrew during or after second-line therapy. Of the remaining 391
      patients, 158 (40.4%) received third-line treatment outside of clinical trials:
      93 received a third-line chemotherapy and 65 a targeted agent. The main reason
      for interrupting third-line treatment was disease progression or death. During
      the same observation period, 25 of 113 patients who completed a third-line
      therapy received a fourth line of treatment. From diagnosis of NSCLC to the end
      of observation, biomarkers were tested in 323 patients (59.7%): epidermal growth
      factor receptor mutations in 315 (58.2%), Kirsten rat sarcoma 2 viral oncogene
      homolog (KRAS) mutations in 83 (15.3%) and Anaplastic lymphoma kinase (ALK)
      translocation in 84 (15.5%). CONCLUSION: In Italian clinical practice, the
      proportion of patients with advanced NSCLC receiving more than 2 treatment lines
      of therapy is not negligible.

PMID- 24925813
TI  - A comparative study of auditory sensitivity in the genus Bufo (amphibia).
AB  - Multi-unit response from the torus semicircularis were recorded to obtain neural
      audiograms for five different species, subspecies and races of the genus
      Bufo:Bufo b.bufo, Bufo b. spinosus, two races of Bufo viridis, and Bufo
      americanus. All of the audiograms were clearly bimodal, with a low frequency peak
      and a high frequency peak. A less pronounced but distinguishable intermediate
      peak seems to be an indication of trimodality. In the low-frequency range, the
      audiograms of the five groups differed little or not at all. There were
      pronounced differences, however, in the high-frequency range. This frequency band
      includes the frequencies of the conspecific mating calls. The best matching
      between call frequency and auditory best frequency was found in the Bufo viridis
      group. While it is likely that factors other than the signal characteristics in
      the vocal repertoire may shape the sensitivity of the auditory system, it is
      notable that those anuran species in which the mating call clearly facilitates
      reproduction have a more pronounced sensitivity peak at the frequencies in their
      mating calls. 

PMID- 24925814
TI  - Early development of aggression in chickens: The relative importance of pecking
      and leaping.
AB  - A longitudinal study (employing a multiple separation technique) of chicks'
      social behavior over the first postnatal month indicated systematic changes in
      their mode of physical interactions. During the first week or so, intersubject
      pecking in same-sex pairs was frequent, and was more likely in birds with a home
      cage advantage (i.e., a prior resident effect). However, there were no sex
      differences in any of the forms of social pecking (head, body, or feet of the
      opponent), and all types showed significant decreases over the period of the
      study. On the contrary, there was a strong effect for sex on rates of aggressive
      leaping, with males exhibiting more leaps than females. Further, there was a
      clear increase in leaping over the first weeks of testing, and something of a
      decline thereafter. These data suggest that in this species the definitive
      expression of aggressive or dominance behavior may be leaping. Early social
      pecking (during a period in which this behavior was at its maximum rate) did not
      predict the subsequent leaping behavior of individuals, but later "leap orders"
      were highly associated with later "peck orders". 

PMID- 24925815
TI  - Pup retrieval and maternal attraction to canine amniotic fluids.
AB  - Three purebred female beagles were observed with both their first and second
      litters. Dams were given three separate simultaneous-choice retrieval tests: In
      addition, the maternal response to amniotic fluids was observed when one pup in
      the litter was treated with amniotic fluids and all other pups were treated with
      water. There was no evidence to suggest that pups were retrieved preferentially
      on the basis of their sex. One female retrieved her own but not alien pups,
      whereas another female made no such discrimination and readily retrieved alien
      pups in addition to her own. Retrieval behavior developed at the time of each
      whelping and normally lasted until the pups were about 5 days old, although a
      bitch would retrieve younger (alien) pups up to 14 days post partum. Maternal
      bitches were strongly attracted towards amniotic fluids: they investigated pups
      daubed with amniotic fluids to a significantly greater extent than control pups
      treated with water. The attraction of maternal females towards amniotic fluids
      developed at the time of each whelping and persisted for up to 30 days, well
      beyond the time that a whelping bitch would normally be exposed to her own fetal
      fluids. A possible role for amniotic fluids in the development of maternal
      behaviour and the establishment of the maternal/puppy bond is discussed. 

PMID- 24925816
TI  - Running response reinforcement by food-hoarding in the golden hamster.
AB  - Partial reinforcement (PR) effects on animal locomotor behavior were studied in
      the golden hamster, using food-hoarding activity as a reinforcer. The first
      experiment demonstrated that hoarding reinforces a running response towards the
      goal section of a straight-alley runway, and that no such learning occurs when
      sated hamsters were not allowed to hoard food. However, a second experiment using
      various partial reinforcement schedules and a continuous reinforcement schedule
      did not give any evidence for the existence of a partial reinforcement
      acquisition effect (PRAE). The third experiment confirmed these results with an
      extended training procedure and showed a slight partial reinforcement extinction
      effect (PREE) mainly in the first sessions of the extinction phase. 

PMID- 24925817
TI  - Genetic predisposition to catatonic behaviour and methylphenidate sensitivity in
      rats.
AB  - To study the relationship between three animal models of schizophrenia, i.e.
      genetically determined akinetic catatonia, stereotypies induced by amphetamine
      like psychostimulators, and behavioural changes in chronic intoxication with such
      stimulators, the frequency of different types of reactions to a functional
      amphetamine analogue, methylphenidate, was studied in wild Norway rats, non
      selected Wistar rats, and Wistar rats bred for predisposition to akinetic
      catatonia. A positive relationship between the predisposition to catatonia and
      the level of stereotypies in a single methylphenidate administration was found in
      wild rats, but not in Wistar bred for catatonia (the latter differed from the non
      selected rats in a higher frequency of "hyperactive" reactions). A closer study
      of catatonia in laboratory rats permitted subdivision into several types
      occurring in selected and non-selected rats both naturally and as a result of
      chronic intoxication with amphetamines. It was found in non-selected Wistar rats
      that there is a positive relationship between some of these types and an
      increased stereotypy level in repeated methylphenidate administration. It is
      concluded that the natural akinetic catatonia and the chronic intoxication with
      amphetamines are two homologous varieties of the same model of schizophrenia,
      while the stereotypies are characteristics of this model. Studies of monoamine
      oxidase (MAO) activity imply a cortical component in the predisposition to
      akinetic catatonia. 

PMID- 24925818
TI  - The effect of social isolation of the rat on open field activity and emergence.
AB  - It has been suggested that naive isolated rats show more "fear responses" than
      group-housed controls. However, in contrast to previous studies, dark conditions
      and low noise levels were used to evaluate the latency to emerge from a small
      chamber into an open field and the subsequent ambulation and rearing behaviour of
      isolated and group-housed rats. The prediction that these conditions would be
      conducive to the rapid development of hyperactivity in isolates was confirmed,
      but there were no significant differences in emergence latency. 

PMID- 24925819
TI  - An assessment of an HIV prevention intervention among people who inject drugs in
      the states of Manipur and Nagaland, India.
AB  - BACKGROUND: The present study describes an assessment of a large-scale
      intervention, "Avahan", using an evaluation framework that assesses the program
      coverage, changes in injection patterns, condom use, and STI and HIV prevalence
      among People Who Inject Drugs (PWID) in two states of India - Manipur and
      Nagaland. METHODS: Program monitoring data and results from two rounds of a cross
      sectional biological and behavioural surveys in 2006 (Round 1) and 2009 (Round 2)
      were used. The sample included 839 and 860 PWIDs from Manipur and 821 and 829
      PWIDs from Nagaland in Round 1 and Round 2 respectively for current analysis.
      Bivariate and multivariate analyses were done to measure the changes in
      behavioural and biological outcomes between the two rounds and to examine the
      association between programme exposure and behavioural outcomes. RESULTS: In
      Manipur, about 77% of the PWIDs were contacted by the peer educators/outreach
      workers every month and about 18% of the PWIDs visited the clinic every month by
      March 2010. In Nagaland, however, the proportion of PWIDs visiting the clinic
      monthly remained low (11% in March 2010). PWIDs in both states were more likely
      to report 'consistent safe injection practice in the last six months' in Round 2
      compared to Round 1 (Manipur: adjusted odds ratio (aOR): 1.88, 95% confidence
      intervals (CI): 1.46-2.43; Nagaland: aOR: 2.35, 95% CI: 1.86-2.80) PWIDs were
      also more likely to report consistent condom use with regular partners in Round
      2. The prevalence of Hepatitis B virus (HBV) increased in Round 2 in Manipur (11%
      vs 6%, p<0.001) and Nagaland (8% vs 6%, p=0.05). The prevalence of Hepatitis C
      virus (HCV) was high and did not change, either in Manipur (67.3% vs 69.9%,
      p=0.42) and Nagaland (14.7% vs 15.1%, p=0.82). Similarly, the prevalence of HIV
      did not change significantly between the two Rounds either in Manipur (27.8% in
      Round 1 vs 29.2% in Round 2, p=0.59) or in Nagaland (1.2% in Round 1 and 1.6% in
      Round 2 of the IBBA, p=0.82). CONCLUSION: Improvements in safe injection
      practices and consistent condom use with regular partners suggest effectiveness
      of prevention efforts. However, increase in HBV prevalence and non-decline in HCV
      and HIV prevalence in both the states also underscore the need to continue and
      intensify targeted interventions (such as Hepatitis B vaccination, needle
      exchange programmes, condom distribution) for long term risk reduction among PWID
      population.

PMID- 24925820
TI  - Perceived risk of methamphetamine among Chinese methamphetamine users.
AB  - BACKGROUND: Methamphetamine use has grown considerably in China in recent years.
      Information about perceptions of risk on methamphetamine is important to
      facilitate health promotion efforts. METHODS: Using both survey data and
      qualitative interview data, the authors evaluate the perceived risk of
      methamphetamine use among Chinese users using a mixed-methods approach. Through
      Respondent Driven Sampling, the authors recruited a sample of 303 methamphetamine
      users in Changsha, China. RESULTS: A majority (59.1%) perceive that infrequent
      methamphetamine use poses no risk to the user, while 11.2% perceive at least
      moderate risk for light use. A majority (56.7%) perceived at least moderate risk
      associated with regular methamphetamine use. Most (82.2%) also perceive
      methamphetamine to be easily obtainable. A path model indicates that perceived
      risk shapes intentions to use and expectations of future use, as does perceived
      availability. Qualitatively, while addiction was the most common risk discussed
      by users, they differed on whether they perceived the drug addictive. Other
      concerns raised by interviewees included impaired cognition, mental health
      problems, physical harm, and social dysfunction. CONCLUSION: While some users
      identify significant risks with methamphetamine, others do not perceive its use
      to be problematic. Collectively, these findings indicate that intervening upon
      perceptions of risk among Chinese methamphetamine users may be a means to
      influence intentions to use.

PMID- 24925821
TI  - The effect of obstructive sleep apnea syndrome and snoring severity to intima
      media thickening of carotid artery.

PMID- 24925823
TI  - Problems with data quality in the reconstruction of evolutionary relationships in
      the Drosophila melanogaster species group: Comments on Yang et al. (2012).

PMID- 24925822
TI  - Risk assessment for obstructive sleep apnea and anxiety in a Pakistani population
      with coronary artery disease.
AB  - PURPOSE: Previous studies in the western world have reported the possible
      association of obstructive sleep apnea (OSA) with anxiety and cardiovascular
      diseases. However, the data from developing countries such as Pakistan remains
      scarce in this regard. The main aim of this study was to investigate the
      prevalence of coronary artery disease (CAD) patients who are at high risk of OSA
      and to determine the association between the risk of OSA and levels of anxiety.
      METHODS: The sample population consisted of 400 participants including 200
      patients, who had been previously diagnosed with CAD, and 200 healthy controls.
      The 200 CAD patients were approached for inclusion in the study on their follow
      ups after their acute symptoms had subsided. The patients were interviewed after
      a mean time period of 13 weeks post event. All patients with lung disease or
      respiratory infection were excluded from the study. The risk of OSA was
      determined using Berlin questionnaire, while the levels of anxiety were measured
      by Beck anxiety inventory scale (BAI). RESULTS: More than half (n = 104) of the
      CAD patients were at high risk of OSA while majority (n = 168) of the healthy
      controls were at low risk. The high risk of OSA was significantly (P < 0.0001)
      more prevalent in CAD patients compared with controls. It was also observed that
      the patients who were at high risk of OSA, among both cases and controls, had
      significantly (P values <0.001) higher levels of anxiety. CONCLUSION: A
      significant proportion of CAD patients are at high risk of OSA in our region.
      Moreover, OSA is also associated with greater levels of anxiety in both healthy
      people and CAD patients.

PMID- 24925824
TI  - Young adult type 1 diabetes care in the West of Ireland: an audit of hospital
      practice.
AB  - BACKGROUND: It is well recognised that management of young adults with type 1
      diabetes (T1DM) poses difficult challenges for physicians and health care
      organisations as a whole. In Ireland and in particular the west of Ireland there
      has been little audit or research on young adults with T1DM and the services
      available to them. DESIGN: In 2011 a retrospective review of this patient
      population in our territory referral centre was carried out. RESULTS: The average
      glycaemic control in this population was poor at 81mmols/mol and diabetes related
      complications were present in 32%. Engagement by this population with services
      was poor with an average of 3 missed clinic appointments over a 24 month period.
      CONCLUSION: These results have prompted a re think of how health care
      professionals can deliver a service that better suits the needs of this
      challenging patient group.

PMID- 24925825
TI  - Response: the index of suspicion for tuberculous pleural effusion should always
      be high.

PMID- 24925826
TI  - Development of a liquid chromatography tandem mass spectrometry method for the
      simultaneous determination of zearalenone, deoxynivalenol and their metabolites
      in pig serum.
AB  - A sensitive and selective liquid chromatography tandem mass spectrometry method
      using negative electrospray ionisation (LC-ESI-MS/MS) was developed for the
      simultaneous determination of zearalenone (ZEN), deoxynivalenol (DON) and their
      metabolites alpha-zearalenol, beta-zearalenol, zearalanone, alpha-zearalanol,
      beta-zearalanol and de-epoxy-deoxynivalenol in pig serum. For method development,
      different sample preparation columns were tested for their suitability for
      extraction and clean up. Finally, preparation of serum samples was carried out
      using OasisTM HLB solid-phase extraction (SPE) columns. The analyte
      concentrations were determined by the use of isotopically labelled internal
      standards (IS). The method was in-house validated for all analytes. Calibration
      graphs (0.3-480 ng/ml) were prepared and high degree of linearity was achieved (r
      >= 0.99). Results for method precision ranged between 2.7 and 21.5 % for inter
      day and between 1.1 and 11.1 % for intra-day. The recoveries were in the range of
      82-131 %. Limits of detection and quantification ranged 0.03-0.71 and 0.08-2.37
      ng/ml, respectively. The method has been successfully used for quantitative
      determination of ZEN, DON and their metabolites in pig serum from a feeding trial
      with practically relevant ZEN and DON concentrations. This method is precise and
      reproducible and can be used as a multi-biomarker method to assess animal
      exposure to these mycotoxins and for diagnosis of intoxications. 

PMID- 24925827
TI  - Reduction of aflatoxins by Rhizopus oryzae and Trichoderma reesei.
AB  - This study evaluated the ability of the microorganisms Rhizopus oryzae (CCT7560)
      and Trichoderma reesei (QM9414), producers of generally recognized as safe (GRAS)
      enzymes, to reduce the level of aflatoxins B1, B2, G1, G2, and M1. The variables
      considered to the screening were the initial number of spores in the inoculum and
      the culture time. The culture was conducted in contaminated 4 % potato dextrose
      agar (PDA) medium, and the residual mycotoxins were determined every 24 h by HPLC
      FL. The fungus R. oryzae has reduced aflatoxins B1, B2, and G1 in the 96 h and
      aflatoxins M1 and G2 in the range of 120 h of culture by approximately 100 %. The
      fungus T. reesei has reduced aflatoxins B1, B2, and M1 in the 96 h and aflatoxin
      G1 in the range of 120 h of culture by approximately 100 %. The highest reduction
      occurred in the middle of R. oryzae culture. 

PMID- 24925828
TI  - Japanese shrine captures Roman goddess!

PMID- 24925829
TI  - Derivation of an oral reference dose (RfD) for the plasticizer, di-(2
      propylheptyl)phthalate (Palatinol(r) 10-P).
AB  - Di-(2-propylheptyl) phthalate (DPHP) is a high molecular weight polyvinyl
      chloride plasticizer. Since increasing production volume and broad utility may
      result in human exposure, an oral reference dose (RfD) was derived from
      laboratory animal data due to the lack of human data. In addition to liver and
      kidney, target organs were the thyroid, pituitary and adrenal glands in rats,
      recognizing that reproductive performance was not altered in two successive
      generations of DPHP-exposed rats. DPHP caused a reduction in pup and maternal
      body weights but not developmental or testicular effects typical of "phthalate
      syndrome." DPHP was not genotoxic. Due to the lack of carcinogenicity data, there
      is inadequate information to assess carcinogenic potential. The RfD of 0.1mg/kg
      day was derived from the human equivalent BMDL10 of 10mg/kg-day for thyroid
      hypertrophy/hyperplasia in male F1 adults from the two-generation study. While in
      utero exposure did not alter sensitivity to thyroid lesions compared to
      subchronic exposures beginning at 6weeks of age, F1 adult males were the longest
      term exposed population. The total uncertainty factor of 100x was comprised of
      intraspecies (10x), study duration (3x), and database (3x) factors but not an
      interspecies factor since rodents are more sensitive than humans to thyroid gland
      effects. 

PMID- 24925830
TI  - Prevalence and predictors of concomitant low sexual desire/interest and new-onset
      erectile dysfunction - a picture from the everyday clinical practice.
AB  - Prevalence and risk factors of concomitant primary low sexual desire/interest
      (LSD/I) and subsequent new-onset erectile dysfunction (ED) in men have been only
      partially investigated. We looked at the sociodemographic and clinical predictors
      of the concomitant condition of primary LSD/I - defined as the reduction in the
      usual level of SD/I which precedes ED or another sexual dysfunction - and new
      onset ED (LSD/I + ED) in a cohort of consecutive Caucasian-European patients
      seeking their first medical help for sexual dysfunction at a single outpatient
      clinic in the everyday clinical practice setting. Data from 439 sexually active
      patients were analysed. Health-significant comorbidities were scored with the
      Charlson Comorbidity Index (CCI). Patients' LSD/I were evaluated according to the
      findings of a comprehensive sexual history. Moreover, patients completed the
      International Index of Erectile Function (IIEF). Descriptive statistics and
      logistic regression models tested the prevalence and predictors of LSD/I + ED as
      compared with ED only. Of the 439 men, LSD/I + ED was observed in 33 (4.2%)
      individuals. One of three men with LSD/I + ED was younger than 40 years. Patients
      complaining of LSD/I + ED or ED alone did not differ in terms of hormonal milieu.
      No significant differences emerged between groups in terms of sexual orientation,
      rates of stable sexual relationships, educational status, recreational habits and
      comorbid sexual dysfunctions. Patients with LSD/I + ED had significantly lower
      IIEF-sexual desire and IIEF-overall satisfaction scores than ED-only individuals
      (all p <= 0.003). At multivariable analysis younger age and severe CCI scores
      emerged as independent predictors of LSD/I + ED (all p <= 0.04). These findings
      showed that primary LSD/I is concomitant with new-onset ED in less than 5% of men
      seeking first medical help. Younger age and severe CCI emerged as independent
      predictors of LSD/I + ED. Patients with both conditions reported an impaired
      overall sexual satisfaction.

PMID- 24925831
TI  - Editorial comment.

PMID- 24925832
TI  - Reply: To PMID 24925831.

PMID- 24925833
TI  - Anatomic complexity quantitated by nephrometry score is associated with prolonged
      warm ischemia time during robotic partial nephrectomy.
AB  - OBJECTIVE: To assess the association between nephrometry score (NS) and prolonged
      warm ischemia time (WIT) in patients undergoing robotic partial nephrectomy (RPN)
      for clinically localized renal masses. METHODS: We queried our prospectively
      maintained kidney cancer database to identify all patients undergoing RPN for
      localized tumors from 2007-2012. Patient and tumor characteristics were compared
      between complexity groups using analysis of variance and chi square tests.
      Multivariate logistic regression models were used to examine the relationship
      between NS complexity and warm ischemia >30 minutes. RESULTS: Three hundred
      seventy-five patients (mean age, 59 +/- 11 years; mean Charlson comorbidity
      index, 1.0 +/- 1.3) undergoing RPN under warm ischemia for clinically localized
      renal tumors (mean tumor size, 3.1 +/- 1.5 cm; mean NS, 6.8 +/- 1.8) met
      inclusion criteria and had NS available. Stratified by complexity, groups
      differed with respect to age at surgery, tumor size, proximity to the hilum,
      collecting system entry, estimated blood loss, and operative time (all P values
      <=.05). Significant differences in mean WIT were observed when comparing low
      (19.4 +/- 12.1 minutes), intermediate (28.6 +/- 12.8 minutes), and high (36.1 +/-
      13.7 minutes) NS complexity groups (P <.0001). Adjusting for confounders,
      patients with intermediate (odds ratio, 2.1; confidence interval, 1.2-3.9) and
      high (odds ratio, 3.7; confidence interval, 1.1-11.8) NS complexity were more
      likely to require prolonged WIT when compared with patients with low complexity
      tumors. CONCLUSION: In our large institutional cohort, quantification of anatomic
      complexity using the NS is associated with WIT >30 minutes in patients undergoing
      RPN for localized renal tumors. This provides further evidence that standardized
      reporting of tumor anatomic complexity affords meaningful outcome comparisons.

PMID- 24925835
TI  - Mechanism of host-guest complex formation and identification of intermediates
      through NMR titration and diffusion NMR spectroscopy.
AB  - The formation of host-guest (H-G) complexes between 1,8
      bis[(diethylgallanyl)ethynyl]anthracene (H) and the N-heterocycles pyridine and
      pyrimidine (G) was studied in solution using a combination of NMR titration and
      diffusion NMR experiments. For the latter, diffusion coefficients of potential
      host-guest structures in solution were compared with those of tailor-made
      reference compounds of similar shape (synthesized and characterized by NMR, HRMS,
      and in part XRD). Highly dynamic behavior was observed in both cases, but with
      different host-guest species and equilibria. With increasing concentrations of
      the pyridine guest, the equilibrium H2?H2kappa(1)-G1?HG2 is observed (in the
      second step a host dimer coordinates one guest molecule); for pyrimidine the
      equilibrium H2->H1kappa(2)-G1?HG2 is observed (the formation of a 1:1 aggregate
      is the second step).

PMID- 24925834
TI  - Prostate-specific antigen density toward a better cutoff to identify better
      candidates for active surveillance.
AB  - OBJECTIVE: To investigate the impact of prostate-specific antigen density (PSAD)
      on existing prostate cancer (PCa) active surveillance (AS) protocols. METHODS:
      Prospectively maintained database on men with PCa who underwent radical
      prostatectomy was reviewed retrospectively. Demographic data and pathologic
      characteristics of patients who fulfilled the AS inclusion criteria under the
      National Comprehensive Cancer Network (NCCN), Prostate Cancer Research
      International Active Surveillance (PRIAS), and University of California, San
      Francisco (UCSF) guidelines were examined. RESULTS: Of 930 patients, 231, 280,
      and 325 fulfilled the NCCN, PRIAS, and UCSF AS criteria, respectively. The
      frequencies of advanced disease on surgical pathology (upstaging and/or
      upgrading) were 31.6% (NCCN), 35.4% (PRIAS), and 34.2% (UCSF) of the study
      cohorts. PSAD was significantly higher in patients with advanced disease compared
      with that in patients with nonadvanced disease in all 3 AS schemas. Modifying the
      PRIAS and UCSF criteria using the NCCN's lower PSAD cutoff of 0.15 ng/mL(2)
      decreased the rates of the advanced disease significantly to 33.5% and 31.4%,
      respectively. Using the receiver operating characteristic curve analysis, the
      optimal PSAD cutoff level for the prediction of advanced disease was 0.085
      ng/mL(2) (sensitivity/specificity of 76.7%/50.6% in NCCN and 75.6%/49.7% in
      PRIAS). CONCLUSION: Among patients with low-risk PCa who underwent radical
      prostatectomy, PSAD is a predictor of advanced disease at the time of surgery.
      Adopting a lower PSAD threshold of 0.085 ng/mL(2) decreased the risk of the
      advanced disease to 17.5%-21.7%. Therefore, PSAD should be part of all AS
      guidelines.

PMID- 24925836
TI  - Candidate lesion-based criteria for defining a positive sacroiliac joint MRI in
      two cohorts of patients with axial spondyloarthritis.
AB  - OBJECTIVE: To determine candidate lesion-based criteria for a positive sacroiliac
      joint (SIJ) MRI based on bone marrow oedema (BMO) and/or erosion in non
      radiographic axial spondyloarthritis (nr-axSpA); to compare the performance of
      lesion-based criteria with global evaluation by expert readers. METHODS: Two
      independent cohorts A/B of 69/88 consecutive patients with back pain aged <=50
      years, with median symptom duration 1.3/10.0 years, were referred for suspected
      SpA (A) or acute anterior uveitis plus back pain (B). Patients were classified
      according to rheumatologist expert opinion based on clinical examination, pelvic
      radiography and laboratory values as having nr-axSpA (n=51), ankylosing
      spondylitis (n=34) or non-specific back pain (n=72). Four blinded readers
      assessed SIJ MRI, recording the presence/absence of SpA by concomitant global
      evaluation of T1-weighted spin echo (T1SE) and short tau inversion recovery
      (STIR) scans and, thereafter, whether BMO and/or erosion were present/absent in
      each SIJ quadrant of each MRI slice. We derived candidate lesion-based criteria
      based on the number of SIJ quadrants with BMO and/or erosion and calculated mean
      sensitivity and specificity for SpA. RESULTS: For both cohorts A/B, global
      assessment showed high specificity (0.95/0.83) compared with the Assessment in
      SpondyloArthritis international Society (ASAS) definition (0.76/0.74). BMO >=3
      (0.89/0.84) or >=4 (0.92/0.87) showed comparably high specificity to global
      assessment. Erosion >=2 and/or BMO >=3 or >=4 were associated with comparably
      high sensitivity to global assessment without affecting specificity. These
      combined criteria showed both higher sensitivity and specificity than the ASAS
      definition. CONCLUSIONS: Lesion-based criteria for a positive SIJ MRI based on
      both BMO and/or erosion performed best for classification of axial SpA,
      reflecting the contextual information provided by T1SE and STIR sequences.

PMID- 24925837
TI  - HCV-associated cryoglobulinaemic vasculitis: triple/dual antiviral treatment
      and/or rituximab?

PMID- 24925838
TI  - Comparison of analytical and numerical analysis of the reference region model for
      DCE-MRI.
AB  - This study compared three methods for analyzing DCE-MRI data with a reference
      region (RR) model: a linear least-square fitting with numerical analysis (LLSQ
      N), a nonlinear least-square fitting with numerical analysis (NLSQ-N), and an
      analytical analysis (NLSQ-A). The accuracy and precision of estimating the
      pharmacokinetic parameter ratios KR and VR, where KR is defined as a ratio
      between the two volume transfer constants, K(trans,TOI) and K(trans,RR), and VR
      is the ratio between the two extracellular extravascular volumes, ve,TOI and
      ve,RR, were assessed using simulations under various signal-to-noise ratios
      (SNRs) and temporal resolutions (4, 6, 30, and 60s). When no noise was added, the
      simulations showed that the mean percent error (MPE) for the estimated KR and VR
      using the LLSQ-N and NLSQ-N methods ranged from 1.2% to 31.6% with various
      temporal resolutions while the NLSQ-A method maintained a very high accuracy
      (<1.0*10(-4) %) regardless of the temporal resolution. The simulation also
      indicated that the LLSQ-N and NLSQ-N methods appear to underestimate the
      parameter ratios more than the NLSQ-A method. In addition, seven in vivo DCE-MRI
      datasets from spontaneously occurring canine brain tumors were analyzed with each
      method. Results for the in vivo study showed that KR (ranging from 0.63 to 3.11)
      and VR (ranging from 2.82 to 19.16) for the NLSQ-A method were both higher than
      results for the other two methods (KR ranging from 0.01 to 1.29 and VR ranging
      from 1.48 to 19.59). A temporal downsampling experiment showed that the averaged
      percent error for the NLSQ-A method (8.45%) was lower than the other two methods
      (22.97% for LLSQ-N and 65.02% for NLSQ-N) for KR, and the averaged percent error
      for the NLSQ-A method (6.33%) was lower than the other two methods (6.57% for
      LLSQ-N and 13.66% for NLSQ-N) for VR. Using simulations, we showed that the NLSQ
      A method can estimate the ratios of pharmacokinetic parameters more accurately
      and precisely than the NLSQ-N and LLSQ-N methods over various SNRs and temporal
      resolutions. All simulations were validated with in vivo DCE MRI data. 

PMID- 24925840
TI  - Responding initiated by pecks on a start key.
AB  - Four pigeons were exposed to various fixed-interval (FI) 30-s conditions which
      included a standard FI30-s condition. In all remaining conditions, a red "start"
      key light began the interval. Completion of various fixed ratios (FR) on the
      start key lit a green "work" key light. In Experiment 1, one peck on the start
      key lit the work key light. Mean postreinforcement pause (PRP) lengthened only
      slightly when the start-key contingency was imposed. In Experiment 2, the start
      key requirement ranged from FR 1 to FR 50. As the FR requirement increased, the
      pause on the work key, called the poststart pause (PSP), decreased for three
      birds at FR 2 but, for all four birds, the PRP and interreinforcement interval
      (IRI) did not lengthen until FR 50. These results support the hypothesis that the
      PRP is a function of the IRI and both are refractory to change, while the PSP is
      seen as a variable that adjusts to different schedule constraints. 

PMID- 24925841
TI  - Group foraging in little egrets (Egretta garzetta): From field evidence to
      experimental investigation.
AB  - Results from both field and experimental foraging studies of little egrets
      (Egretta garzetta) are used to discuss the relationship between flocking, prey
      density and foraging efficiency. In the field, the latter was affected by group
      size. The two parameters studied, striking efficiency (percentage of successful
      pecks) and the number of captures per minute improved in large groups. On the
      other hand, only in one of two field sites did the results reveal an improvement
      under the form of a reduced variance in striking efficiency, of birds in a small
      group as compared to solitary birds. During the experiments, the number of
      captures per minute was higher in a pool with high prey density than in situation
      with low prey density, while differences were not significant when comparing
      medium with low or high prey density. Group size had no effect on capture rate.
      Striking efficiency, searching effort and prey selectivity were not affected by
      flocking or prey density. The possible benefits of flock feeding are discussed. 

PMID- 24925839
TI  - Feasibility of fat-saturated T2-weighted magnetic resonance imaging with slice
      encoding for metal artifact correction (SEMAC) at 3T.
AB  - BACKGROUND AND PURPOSE: Fluid-sensitive MR imaging in postoperative evaluation is
      important, however, metallic artifacts is inevitable. The purpose is to
      investigate the feasibility of fat-saturated slice encoding for metal artifact
      correction (SEMAC)-corrected T2-weighted magnetic resonance (MR) at 3T in
      patients with spinal prostheses. METHODS: Following institutional review board
      approval, 27 SEMAC-encoded spinal MRs between September 2012 and October 2013 in
      patients with spinal metallic prostheses were analyzed. The MR images were
      scanned on a 3T MR system including SEMAC-corrected and uncorrected fast spin
      echo (FSE) T2-weighted MR images with fat-saturation. Two musculoskeletal
      radiologists compared the image sets and qualitatively analyzed the images using
      a five-point scale in terms of artifact reduction around the prosthesis,
      visualization of the prosthesis and pedicle, and intervertebral neural foramina.
      Quantitative assessments were performed by calculating the ratio of signal
      intensity from the fixated vertebra and that from upper level vertebra. For
      statistical analyses, paired t-test was used. RESULTS: Fat-saturated SEMAC
      corrected T2-weighted MR images enabled significantly improved metallic artifact
      reduction (P<0.05). Quantitative evaluation of the signal intensity ratio of
      screw-fixated vertebra and upper level vertebra showed a significantly lower
      ratio on fat-saturated SEMAC images (P<0.05), however, the high signal intensity
      of signal pile-up could be not completely corrected. CONCLUSION: SEMAC correction
      in fat-suppressed T2-weighted MR images can overcome the signal loss of metallic
      artifacts and provide improved delineation of the pedicle screw and peri
      prosthetic region. Signal pile-up, however, could not be corrected completely,
      therefore readers should be cautious in the evaluation of marrow around the
      prosthesis.

PMID- 24925842
TI  - Seasonality in the flight activity of the tropical bat Rhinopoma hardwickei under
      natural photoperiod.
AB  - The activity cycle of a colony of about 1500 bats Rhinopoma hardwickei was
      studied in 1978-1979 in Madurai, India. Variations in the times of emergence of
      foraging paralleled variations in sunset and return to the roosting paralleled
      sunrise. The releasing stimulus for departure of the first outflyer on clear
      evenings is the crossing of a lower threshold value of its relative decrease.
      Return to the roost usually occurs at a lower light intensity than the departure.
      In summer the nightly rate of emergence is relatively higher than in winter. The
      seasonal changes of phase angle differences of onset (Psi0) and end (Psie) of
      activities are roughly mirror images. The time of midpoint of foraging activity
      however, stays relatively constant. 

PMID- 24925843
TI  - Decrease in cow-calf attachment after weaning.
AB  - Experiments were undertaken to measure attraction of suckler calves to their dams
      after separation for abrupt weaning. On days 0, 2, 7 and 20 after weaning in
      experiment 1 and on days 1, 9, 16, 24 and 35 after weaning in experiment 2,
      calves were observed in a pen where they could stay either near the dam or near
      another familiar cow or calf. On days 0, 2, 7, 20 and 35, calves and their dams
      were reunited for 2 min. Calves showed a preference for the dam to another cow up
      to day 24 and to a calf up to day 9 only. From day 20, cows rejected their calves
      at suckling. It is concluded that the calves remained attracted by their dams for
      at least three weeks after weaning while the cows already rejected them. In
      addition, attraction between calves increased after weaning. 

PMID- 24925844
TI  - Influence de l'environnement pre-imaginal et precoce dans le choix du site de
      nidification de Pachycondyla (=Neoponera) villosa (Fabr.) (formicidae,
      ponerinae).
AB  - In the Biosphera Reserve of Sian Ka'an, State of Quintana Roo in Mexico, it was
      observed that Pachycondyla villosa nest almost exclusively in Bromeliad epiphytes
      Aechmea bracteata. It is possible that winged females seek this plant to build
      their society. From this fact two hypothesis may be formulated. Two lots
      comprising workers and winged females were tested. In each case, the lot
      controlled comprised of individuals found in nature (societies settled on
      Aechmea). The tested lots were produced and bred in laboratory. The first lot was
      put in contact with a piece of Schomburgkia tibicinis, the second lot had no
      contact with a plant. At the time of the experiment, each lot was faced with a
      choice between two tubes. One contained a piece of Aechmea, the other was empty
      (1st series of tests), or contained a piece of Schomburgkia (2nd series of
      tests). The first series of tests permits to show that controls (individuals that
      have contact with Aechmea in nature) settle in tubes containing a piece of
      Aechmea whereas individuals from the other two lots settle indiscriminately in
      either of the tubes. The second series of tests permits to show that controls
      also settle in the tube containing Aechmea, that individuals raised in contact
      with Schomburgkia choose the tube containing this plant and that individuals
      raised in the absence of plant contact settle indiscriminately in either of the
      tubes. The influence of the original environmental influence on individuals in
      the choice between two types of tubes is thus demonstrated. This influence is due
      to an imprinting during larval life, and strenghened at the beginning of imago
      life. 

PMID- 24925845
TI  - Behavioural strategies of aggressive and non-aggressive male mice in response to
      inescapable shock.
AB  - The effect of exposure to inescapable long-duration shocks of moderate intensity
      on intershock activity and on subsequent escape or avoidance performance was
      studied in aggressive and non-aggressive male mice. The activity of the non
      aggressive mice was severely suppressed during the inescapable shock session,
      while that of the aggressive males was hardly influenced. The decremental effect
      of prior shock exposure on subsequent response latency and activity in an active
      two-way escape or avoidance task was greater in the non-aggressive than in the
      aggressive mice. There was no evidence that learned inactivity or learned
      helplessness (an associative deficit) could explain the results. Instead,
      individual differences in behavioural strategy in response to threatening
      situations appeared to account for the effects of inescapable shock. Aggressive
      male mice predominantly adopted an active behavioural strategy in challenging
      situations, which resulted in persistent attempts to exercise control over the
      external situation and hence in a sustained tendency to initiate responses. Non
      aggressive mice primarily assumed a passive strategy; their tendency to exercise
      control was low, which readily resulted in a reduced tendency to initiate
      responses. 

PMID- 24925846
TI  - Responses to a novel food acquisition task in three species of lemurs.
AB  - In order to study learning and social processes in lemurs, a food acquisition
      task was presented to three groups: Lemur macaco, L. fulvus and L. catta. The lid
      of a box had to be pivoted horizontally in order to expose figs contained
      therein. Individuals in all three groups learned the task, but they showed only
      limited comprehension. In L. macaco, two adult females learned, with one female
      showing increasing aggressive monopolization of the new food-source. In L.
      fulvus, two adult males learned, and one of them increasingly prevented the other
      from approaching. In L. catta, the adult female frequently threatened away the
      most efficient opener - a young adult male. The simultaneous presentation of two
      boxes led to a more equal distribution of the figs. Social processes revealed in
      the test situation included female dominance in L. macaco and L. catta, and an
      intermale dominance relationship in L. fulvus. The experimental situation also
      highlighted the privileged position of the offspring of the dominant female in L.
      macaco, reduced competitiveness of females with very young infants in L. fulvus,
      and a general tolerance towards others in L. fulvus. 

PMID- 24925847
TI  - The role of shifting in choice behavior of pigeons on a two-armed bandit.
AB  - Pigeons (Columba livia) were confronted with a problem in choice known as the two
      armed bandit (TAB): two concurrent discrete trials random-ratio schedules in
      which the good side changes randomly from day to day. In the first experiment a
      substantial proportion of the birds' choices were contrary to those predicted by
      immediate maximization. Under a variety of parameter settings the pigeons chose
      the bad side more often than expected by immediate maximization. The hypothesis
      was advanced that shifting, that is, the tendency to avoid the most recently
      visited location, was responsible for limiting the number of choices on the good
      side of the TAB. Experiments 2-4 examined this hypothesis. The first of these
      experiments compared the accuracy on win-shift vs win-stay trials, and lose-shift
      vs lose-stay. When the response keys were at opposite sides of the operant
      chamber (keys-far), as in the first TAB experiment, there was a significant
      tendency to shift. This tendency was not present when the keys were close
      together (keys-close), in Experiment 3. Experiment 4 compared TAB performance in
      the original keys-far situation with that in the keys-close chamber. The
      proportion of choices on the good side of the TAB increased faster and attained a
      higher level for the keys-close group, and the proportion of choices which were
      shifts from one side to the other was smaller. A higher proportion of individual
      choices in the keys-close condition could be accounted for by immediate
      maximization. 

PMID- 24925848
TI  - Hamsters (Mesocricetus auratus ) use spatial memory in foraging for food to
      hoard.
AB  - We have collected evidence that a hoarding species of rodent, the Syrian golden
      hamster (Mesocricetus auratus), uses spatial memory in foraging for food to
      hoard. Before each trial, we baited the same four arms of a modified seven arm
      radial maze with sunflower seeds. During the trial we gave each hamster 15-min
      access to the maze and observed its behaviour. Typically their behaviour
      comprised two phases: Upon entering the maze the hamsters frequently explored the
      arms of the maze, not eating seeds nor storing seeds in their cheek pouches. This
      exploration was followed by food gathering. In doing this, the hamsters generally
      visited the baited arms in succession, placing all the seed that they found in an
      arm into their cheek pouches. While gathering food, the hamsters seldom revisited
      depleted arms, suggesting that they remembered the locations of depleted food
      sites. 

PMID- 24925849
TI  - Undermatching, melioration and the discrimination of local reinforcer rates.
AB  - Melioration theory suggests that performance in choice situations arises from a
      process in which subjects allocate more time to alternatives that provide the
      higher local rate of reinforcers. If this process is unconstrained (as in
      concurrent aperiodic schedules), melioration predicts a strict equality between
      molar time-allocation (and, as a result, response-allocation) ratios and molar
      ratios of overall obtained reinforcers on concurrent variable-interval schedules.
      The available data, however, suggest that log behavior measures are nearer to
      indifference (called undermatching that predicted by this theory. The
      modification of melioration theory suggested here shows that, if animals cannot
      discriminate local reinforcer-rate differences below a fixed threshold,
      undermatching is predicted, and the degree of undermatching depends on the
      absolute size of the threshold. It also predicts the finding that the sensitivity
      of behavior ratios to changes in reinforcer ratios falls with decreasing overall
      reinforcer rates. 

PMID- 24925850
TI  - Effects of a response-reinforcer relation on elicited pecking.
AB  - Three pigeons were exposed for 22 sessions to a variant of a multiple variable
      time 1-min extinction reinforcement schedule in the presence of a white key. A
      1.5-s stimulus change (red) preceded each 1-min component during which food was
      delivered and a 1.5-s stimulus change (green) preceded each extinction component.
      The variable-time 1-min schedule was then changed to a variable-interval 1-min
      schedule for several sessions and then returned to variable time 1-min. During
      the first exposure to noncontingent reinforcer delivery, two of the three birds
      pecked frequently during the 1.5-s red stimulus but not during the other
      components. The third bird did not keypeck. The addition of a response-reinforcer
      relation resulted in all three birds pecking during the red stimulus as well as
      during the white stimuli. Pecking rates were usually highest during red. Response
      rates during green remained low. The subsequent removal of the response
      contingency resulted in a decrease in responding during white, and for two of the
      three birds, a decrease in responding during the red stimulus. The results
      support an interpretation of signal key pecking in stimulus separation procedures
      as elicited key pecking controlled by the stimulus-reinforcer relation. 

PMID- 24925854
TI  - Identification and characterization of progesterone- and estrogen-regulated
      MicroRNAs in mouse endometrial epithelial cells.
AB  - In endometrial epithelial cells, progesterone (P4) functions in regulating the
      cell structure and opposing the effects of estrogen. However, the mechanisms of
      P4 that oppose the effects of estrogen remain unclear. MicroRNAs (miRNAs) are
      important posttranscriptional regulators that are involved in various
      physiological and pathological processes. Whether P4 directly induces miRNA
      expression to antagonize estrogen in endometrial epithelium is unclear. In this
      study, total RNAs were extracted from endometrial epithelium of ovariectomized
      mice, which were treated with estrogen alone or a combination of estrogen and P4.
      MicroRNA high-throughput sequencing with bioinformatics analysis was used to
      identify P4-induced miRNAs, predict their potential target genes, and analyze
      their possible biological functions. We observed that 146 mature miRNAs in
      endometrial epithelial cells were significantly upregulated by P4. These miRNAs
      were extensively involved in multiple biological processes. The miRNA-145a
      demonstrated a possible function in the antiproliferative action of P4 on
      endometrial epithelial cells. 

PMID- 24925855
TI  - Paricalcitol, a vitamin d receptor activator, inhibits tumor formation in a
      murine model of uterine fibroids.
AB  - We examined the antitumor and therapeutic potentials of paricalcitol, an analog
      of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine
      fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid
      cells and animal models. We found that paricalcitol has potential to reduce the
      proliferation of the immortalized human uterine fibroid cells. For the in vivo
      study, we generated subcutaneous tumors by injecting the Eker rat-derived uterine
      leiomyoma cell line (ELT-3) rat uterine fibroid-derived cell line in athymic nude
      mice supplemented with estrogen pellets. These mice were administered with
      vehicle versus paricalcitol (300 ng/kg/d) or 1,25-dihydroxyvitamin D3 (500
      ng/kg/d) for 4 consecutive weeks, and the data were analyzed. We found that while
      both paricalcitol and 1,25-dihydroxyvitamin D3 significantly reduced fibroid
      tumor size, the shrinkage was slightly higher in the paricalcitol-treated group.
      Together, our results suggest that paricalcitol may be a potential candidate for
      effective, safe, and noninvasive medical treatment option for uterine fibroids. 

PMID- 24925856
TI  - Transabdominal ultrasound-guided injection of methotrexate in the treatment of
      ectopic interstitial pregnancies.
AB  - PURPOSE: In a retrospective observational study, we evaluated the feasibility and
      safety of medical therapy with transabdominal ultrasound-guided injection of
      methotrexate (MTX) into the gestational sac (GS) in patients with interstitial
      ectopic pregnancies. METHODS: Fourteen interstitial ectopic pregnancies were
      treated with transabdominal ultrasound-guided injection of MTX (25 mg). All
      patients were hemodynamically stable. In all patients, the 10-cm distance between
      the GS and vaginal fornices was >=10 cm, making transvaginal injection difficult.
      To evaluate feasibility and safety of the procedure, we assessed complications
      clinically and with imaging during a 1-year follow-up. RESULTS: In all 14
      patients, MTX injected locally into the GS successfully terminated the
      interstitial pregnancy, thereby avoiding surgery. There was no complications
      during follow-up. CONCLUSIONS: The successful outcome in our patients suggests
      that the transabdominal route is feasible and safe as a nonsurgical option for
      terminating an ectopic interstitial pregnancy in patients in whom the
      transvaginal route is contraindicated or difficult, provided the patients are
      properly selected and operators have sufficient experience with the technique.

PMID- 24925857
TI  - In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in
      skeletal muscle at 3T.
AB  - PURPOSE: To characterize the chemical exchange saturation transfer (CEST)-based
      technique to measure free creatine (Cr), a key component of muscle energy
      metabolism, distribution in skeletal muscle with high spatial resolution before
      and after exercise at 3T. MATERIALS AND METHODS: CrCEST saturation parameters
      were empirically optimized for 3T. CEST, T2 , magnetization transfer ratio (MTR),
      and (31) P magnetic resonance spectroscopy (MRS) acquisitions of the lower leg
      were performed before and after mild plantar flexion exercise on a 3T whole-body
      MR scanner on six healthy volunteers. RESULTS: The feasibility of imaging Cr
      changes in skeletal muscle following plantar flexion exercise using CrCEST was
      demonstrated at 3T. This technique exhibited good spatial resolution and was able
      to differentiate differences in muscle use among subjects. The CrCEST results
      were compared with (31) P MRS results, showing good agreement in the Cr and PCr
      recovery kinetics. A relationship of 0.45% CrCESTasym /mM Cr was observed across
      all subjects. CONCLUSION: It is demonstrated that the CrCEST technique could be
      applied at 3T to measure dynamic changes in creatine in muscle in vivo. The
      widespread availability and clinical applicability of 3T scanners has the
      potential to clinically advance this method.

PMID- 24925858
TI  - The accuracy of the out-of-field dose calculations using a model based algorithm
      in a commercial treatment planning system.
AB  - The out-of-field dose can be clinically important as it relates to the dose of
      the organ-at-risk, although the accuracy of its calculation in commercial
      radiotherapy treatment planning systems (TPSs) receives less attention. This
      study evaluates the uncertainties of out-of-field dose calculated with a model
      based dose calculation algorithm, anisotropic analytical algorithm (AAA),
      implemented in a commercial radiotherapy TPS, Varian Eclipse V10, by using Monte
      Carlo (MC) simulations, in which the entire accelerator head is modeled including
      the multi-leaf collimators. The MC calculated out-of-field doses were validated
      by experimental measurements. The dose calculations were performed in a water
      phantom as well as CT based patient geometries and both static and highly
      modulated intensity-modulated radiation therapy (IMRT) fields were evaluated. We
      compared the calculated out-of-field doses, defined as lower than 5% of the
      prescription dose, in four H&N cancer patients and two lung cancer patients
      treated with volumetric modulated arc therapy (VMAT) and IMRT techniques. The
      results show that the discrepancy of calculated out-of-field dose profiles
      between AAA and the MC depends on the depth and is generally less than 1% for in
      water phantom comparisons and in CT based patient dose calculations for static
      field and IMRT. In cases of VMAT plans, the difference between AAA and MC is
      <0.5%. The clinical impact resulting from the error on the calculated organ doses
      were analyzed by using dose-volume histograms. Although the AAA algorithm
      significantly underestimated the out-of-field doses, the clinical impact on the
      calculated organ doses in out-of-field regions may not be significant in practice
      due to very low out-of-field doses relative to the target dose. 

PMID- 24925859
TI  - In vitro and in vivo anti-angiogenic effects of hydroxyurea.
AB  - Hydroxyurea (HU), or hydroxycarbamide, is used for the treatment of some
      myeloproliferative and neoplastic diseases, and is currently the only drug
      approved by the FDA for use in sickle cell disease (SCD). Despite the relative
      success of HU therapy for SCD, a genetic disorder of the hemoglobin beta chain
      that results in red-cell sickling, hemolysis, vascular inflammation and recurrent
      vasoocclusion, the exact mechanisms by which HU actuates remain unclear. We
      hypothesized that HU may modulate endothelial angiogenic processes, with
      important consequences for vascular inflammation. The effects of HU (50-200 MUM;
      17-24 h) on endothelial cell functions associated with key steps of angiogenesis
      were evaluated using human umbilical vein endothelial cell (HUVEC) cultures.
      Expression profiles of the HIF1A gene and the miRNAs 221 and 222, involved in
      endothelial function, were also determined in HUVECs following HU administration
      and the direct in vivo antiangiogenic effects of HU were assessed using a mouse
      Matrigel-plug neovascularization assay. Following incubation with HU, HUVECs
      exhibited high cell viability, but displayed a significant 75% inhibition in the
      rate of capillary-like-structure formation, and significant decreases in
      proliferative and invasive capacities. Furthermore, HU significantly decreased
      HIF1A expression, and induced the expression of miRNA 221, while downregulating
      miRNA 222. In vivo, HU reduced vascular endothelial growth factor (VEGF)-induced
      vascular development in Matrigel implants over 7 days. Findings indicate that HU
      is able to inhibit vessel assembly, a crucial angiogenic process, both in vitro
      and in vivo, and suggest that some of HU's therapeutic effects may occur through
      novel vascular mechanisms.

PMID- 24925861
TI  - Tissue damage modeling in gene electrotransfer: the role of pH.
AB  - Optimal gene electrotransfer (GET) requires a compromise between maximum
      transgene expression and minimal tissue damage. GET in skeletal muscle can be
      improved by pretreatment with hyaluronidase which contributes to maximize
      transgene uptake and expression. Nevertheless, tissue damage remains severe close
      to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the
      role of pH in tissue damage in GET protocols through in vivo modeling using a
      transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and
      intravital microscopy, and in silico modeling using the Poisson-Nernst-Planck
      equations for ion transport. DSC intravital microscopy reveals the existence of
      pH fronts emerging from both electrodes and that these fronts are immediate and
      substantial thus giving rise to tissue necrosis. Theoretical modeling confirms
      experimental measurements and shows that in GET protocols whether with or without
      hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage
      near the electrodes. It also predicts that an optimal efficiency in GET
      protocols, that is a compromise between obtaining maximum electroporated area and
      minimal tissue damage, is achieved when the electric field applied is near 183
      V/cm in a GET protocol and 158 V/cm in a hyaluronidase+GET protocol.

PMID- 24925862
TI  - Blood-stained colostrum and human milk during pregnancy and early lactation.
AB  - Blood-stained colostrum occurs occasionally during pregnancy and lactation due to
      a conspicuous increase in lobuloalveolar growth. We report on a case of bilateral
      frank blood-stained colostrum secreted during pregnancy and early postpartum,
      emphasizing the transitory nature of this condition and the need to reinforce
      breastfeeding. 

PMID- 24925863
TI  - Development of responsiveness to the individual maternal "clucking" by domestic
      chicks (Gallus gallus domesticus).
AB  - Sixty-nine chicks, brooded by hens, were given the choice of approaching the
      clucking sound of the familiar hen or another clucking source. The effects of age
      and prenatal experience of clucking on the responsiveness to their hen's clucking
      were also investigated. Eighty-three percent of all chicks tested chose the
      familiar hen clucking after a certain age. By 4 days of age, 29% of artificially
      incubated chicks approached the clucking of a familiar hen. Seventy-four percent
      of naturally incubated chicks and 89% of chicks artificially incubated until
      pipping and then naturally incubated, showed this discrimination. This
      corresponds well to the natural situation, in which the hen remains in the nest
      with the chicks for up to 3 days after hatching. The results also indicate that
      late prenatal experience of the maternal call is of importance for the later
      responsiveness to this call. 

PMID- 24925864
TI  - The effect of the type of opponent in tests of murine aggression.
AB  - The interactions between isolated resident mice and anosmic, juvenile, submissive
      and dominant intruders were studied; the responses of intruder mice to being
      attacked and the distribution of bites on these subjects were investigated.
      Anosmic, juvenile and (trained) submissive intruders did not attack residents;
      they did, however, show differences both in thir responses to being attacked and
      their ability to avoid bites to particular regions of their body surface. These
      differences are likely to make it difficult to extrapolate between tests that
      employ different types of intruder. Trained dominant intruders showed substantial
      attack on resident mice and a very different pattern of attack was generated by
      this type of encounter. The study confirms that, while "standard opponents" are
      useful means of assessing aggressive motivation, the pattern of fighting they
      produce differs depending on their background. 

PMID- 24925865
TI  - Effects of lateral amygdala lesions on the responses to novelty in mice.
AB  - Bilateral electrolytic lesions restricted to the lateral, basolateral and
      basomedial amygdaloid nuclei in mice produced a lack of avoidance responses
      towards novel stimuli. While controls showed avoidance and burying reactions to a
      novel object introduced into their familiar environment, lesioned mice displayed
      a high number of approach responses and a low level of burying reactions.
      Furthermore, when given the opportunity to move around freely in simultaneously
      presented novel and familiar places, control mice at first exhibited avoidance
      reactions to the novel environment before showing novelty preference. There were
      no avoidance reactions in lesioned mice. These data are consistent with the
      hypothesis that amygdala plays a specific role in the regulation of defensive
      reactions. 

PMID- 24925866
TI  - Nest-box choice in the laboratory mouse: Preferences for nest-boxes differing in
      design (size and/or shape) and composition.
AB  - The purpose of this paper is to introduce two experimental paradigms used for a
      laboratory approach to spatial choice behaviour in the mouse. The experimental
      procedure involves a free-choice spatial situation which allows the development
      of a long-term behavioural process. The animal is placed in an arena containing
      two or more nest-boxes to be chosen as nest-sites. These may differ in certain
      characteristics, such as size, shape, or composition. The experimental procedures
      are: (1) a series of independent successive choice tests, or "paired
      comparisons"; (2) a dependent successive choice test, or "forced progressive
      elimination ranking". Both procedures have been used to study nest-box choice in
      mice according to spatial parameters. In Experiment I, "paired comparisons" were
      used to evaluate the strength of individual preferences for nest-boxes differing
      in design (size and/or shape), according to whether nest-boxes were open or
      closed. In Experiment II, the second method was used to analyse individual
      preferential ranking patterns with series of nest-boxes differing in design or
      composition. The results of the two types of experiment were complementary
      regarding the design (size and shape) of the nest-boxes: highest in order of
      preference were small narrow-sided nest-boxes, followed by small square ones,
      then the small circular one, and last the big circular ones. Experiment I proved
      in particular the role of closure in reinforcing the strength of preferences. In
      Experiment II, on the other hand, the constituent materials did not appear to
      have any clear influence on preferential ranking patterns for the nest-boxes
      differing in design; nevertheless, a positive correlation was noted between the
      classification of objects made of different materials, and the degree of darkness
      afforded by these materials. 

PMID- 24925874
TI  - Retinoid signaling is necessary for, and promotes long-term memory formation
      following operant conditioning.
AB  - Retinoic acid, a metabolite of vitamin A, is proposed to play an important role
      in vertebrate learning and memory, as well as hippocampal-dependent synaptic
      plasticity. However, it has not yet been determined whether retinoic acid plays a
      similar role in learning and memory in invertebrates. In this study, we report
      that retinoid signaling in the mollusc Lymnaea stagnalis, is required for long
      term memory formation following operant conditioning of its aerial respiratory
      behaviour. Animals were exposed to inhibitors of the RALDH enzyme (which
      synthesizes retinoic acid), or various retinoid receptor antagonists. Following
      exposure to these inhibitors, neither learning nor intermediate-term memory
      (lasting 2 h) was affected, but long-term memory formation (tested at either 24
      or 72 h) was inhibited. We next demonstrated that various retinoid receptor
      agonists promoted long-term memory formation. Using a training paradigm shown
      only to produce intermediate-term memory (lasting 2 h, but not 24 h) we found
      that exposure of animals to synthetic retinoids promoted memory formation that
      lasted up to 30 h. These findings suggest that the role of retinoids in memory
      formation is ancient in origin, and that retinoid signaling is also important for
      the formation of implicit memories, in addition to its previously demonstrated
      role in hippocampal-dependent memories.

PMID- 24925875
TI  - A multi-component two-phase flow algorithm for use in landfill processes
      modelling.
AB  - This paper describes the finite difference algorithm that has been developed for
      the flow sub-model of the University of Southampton landfill degradation and
      transport model LDAT. The liquid and gas phase flow components are first
      decoupled from the solid phase of the full multi-phase, multi-component landfill
      process constitutive equations and are then rearranged into a format that can be
      applied as a calculation procedure within the framework of a three dimensional
      array of finite difference rectangular elements. The algorithm contains a source
      term which accommodates the non-flow landfill processes of degradation, gas
      solubility, and leachate chemical equilibrium, sub-models that have been
      described in White and Beaven (2013). The paper includes an illustration of the
      application of the flow sub-model in the context of the leachate recirculation
      tests carried out at the Beddington landfill project. This illustration
      demonstrates the ability of the sub-model to track movement in the gas phase as
      well as the liquid phase, and to simulate multi-directional flow patterns that
      are different in each of the phases. 

PMID- 24925876
TI  - Experimental evidence of fluid secretion of rabbit lacrimal gland duct
      epithelium.
AB  - PURPOSE: To investigate the osmotic water permeability of lacrimal gland (LG)
      duct epithelium by means of calculation of filtration permeability and to
      investigate LG ductal fluid secretion. METHODS: Experiments were performed on
      isolated rabbit LG duct segments maintained in short-term culture. Osmotically
      determined fluid movement or fluid secretion into the closed intraluminal space
      of cultured LG interlobular ducts was analyzed using video microscopic technique.
      RESULTS: The end of the LG ducts sealed after overnight incubation forming a
      closed luminal space. For the calculation of osmotic water permeability, ducts
      were initially perfused with isotonic HEPES buffered solution, and then with
      hypotonic HEPES buffered solution. Filtration permeability was calculated from
      the initial slope of the relative volume increase. Secretory responses to
      carbachol or to forskolin stimulation were also investigated. Forskolin
      stimulation resulted in a rapid and sustained secretory response in both
      solutions. Forskolin-stimulated fluid secretion was completely inhibited by
      bumetanide both in HEPES buffered and in HCO3 (-)/CO2 buffered solutions,
      suggesting the central role of Na(+)-K(+)-2Cl(-) cotransporter type 1 (NKCC1).
      Administration of carbachol initiated a rapid but short secretory response in
      both HEPES buffered and in HCO3 (-)/CO2 buffered solutions. Atropine completely
      abolished the carbachol-evoked fluid secretion. CONCLUSIONS: A new method was
      introduced to investigate LG duct function. Water permeability of rabbit LG duct
      epithelium was measured by calculating filtration permeability. Fluid secretion
      of LG duct cells induced by carbachol or forskolin was also demonstrated. These
      results provide calculated values of lacrimal duct osmotic permeability and
      direct experimental evidence of LG duct fluid secretion.

PMID- 24925877
TI  - Blue light-induced oxidative stress in human corneal epithelial cells: protective
      effects of ethanol extracts of various medicinal plant mixtures.
AB  - PURPOSE: To investigate the effects of visible light on human corneal epithelial
      cells and the impact of natural antioxidants on oxidative stress produced by
      overexposure to light. METHODS: Light-emitting diodes with various wavelengths
      (410-830 nm) were used to irradiate human corneal epithelial cells, and cell
      viability was assessed. The production of reactive oxygen species (ROS) was
      analyzed using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). Ethyl alcohol
      (EtOH) extracts were prepared from mixtures of medicinal plants. After
      application of the EtOH extracts, the free radical scavenging activity was
      measured using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay.
      The induction of antioxidant enzymes including heme oxygenase-1 (HO-1),
      peroxiredoxin-1 (Prx-1), catalase (CAT), and superoxide dismutase-2 (SOD-2) by
      the extracts was evaluated by reverse transcription-polymerase chain reaction and
      Western blotting. The ability of the extracts to inhibit ROS was also analyzed
      using DCF-DA. RESULTS: The viability of corneal epithelial cells was diminished
      after irradiation of blue light (above 10 J at 410 nm and 50 J at 480 nm).
      Reactive oxygen species production was induced by irradiation at 410 and 480 nm
      at doses of 5 J/cm(2) and higher. Ethyl alcohol extracts had potent radical
      scavenging activity. Application of the extracts not only increased the
      expression of HO-1, Prx-1, CAT, and SOD-2, but it also attenuated the ROS
      production induced by blue light in a dose-dependent manner. CONCLUSIONS:
      Overexposure to blue light (410-480 nm) may have a harmful effect on human
      corneal epithelial cells compared with other visible light wavelengths. Medicinal
      plant extracts can have potent protective effects on blue light-induced oxidative
      stress.

PMID- 24925878
TI  - British Ocular Syphilis Study (BOSS): 2-year national surveillance study of
      intraocular inflammation secondary to ocular syphilis.
AB  - PURPOSE: The British Ocular Syphilis Study (BOSS) is the first national
      prospective epidemiological study of intraocular syphilis (IOS) in light of the
      global increase in early syphilis (ES). The aims were to ascertain the UK
      incidence, demographics, clinical features, laboratory data, and posttreatment
      visual outcomes of patients with IOS. METHODS: Prospective study of IOS, reported
      through the national reporting system (British Ocular Surveillance Unit) from
      2009 to 2011. Case definition was any adult presenting with intraocular
      inflammation in ES. RESULTS: A total of 41 new cases (63 eyes) of IOS were
      reported, giving an annual incidence of 0.3 per million UK adult population. Mean
      age was 48.7 years (range, 20.6-75.1); 90.2% were male. All had RPR/VDRL titers
      of >=1:16. Bilateral ocular involvement occurred in 56%; in unilateral cases, the
      left eye was more commonly affected (P = 0.009). Mean presenting logMAR visual
      acuity was 0.52 (20/63 Snellen; range, -0.2 to 2.30 logMAR). Panuveitis was the
      commonest diagnosis, seen in 41.3%, and isolated anterior uveitis was uncommon
      (9.5%). Subgroup analysis between HIV-positive and -negative patients found no
      significant differences in terms of proportion of bilateral disease, presenting
      or post treatment acuity. HIV-positive patients had higher rates of panuveitis.
      At final follow-up, 92.1% had visual acuity >= 0.3 logMAR (20/40 Snellen) after
      antibiotic therapy. CONCLUSIONS: This study is the largest prospective series of
      ocular syphilis in the post-penicillin era. It confirms good visual outcomes for
      treated IOS, irrespective of HIV status or time to presentation. The study
      identified an unexpected preponderance for left eye involvement in uniocular
      cases; which is unexplained.

PMID- 24925879
TI  - Full-field chromatic pupillometry for the assessment of the postillumination
      pupil response driven by melanopsin-containing retinal ganglion cells.
AB  - PURPOSE: The postillumination pupil response (PIPR) is produced by intrinsically
      photosensitive retinal ganglion cells (ipRGCs). We aimed to refine the testing
      conditions for PIPR by investigating whether a greater PIPR can be induced using
      full-field light stimuli of shorter duration and lower intensity than that
      produced by existing protocols that use central-field stimuli. METHODS: Pupil
      response was recorded with an eye tracker in 10 visually-normal subjects. Red and
      blue light stimuli were presented using a Ganzfeld system. In Experiment 1
      (intensity trials), PIPR was induced using 1-second full-field stimuli of
      increasing intensities from 0.1 to 400 cd/m(2) (11 steps). For comparison, PIPR
      also was induced using a 60 degrees  * 90 degrees  central-field blue stimulus of
      400 cd/m(2). In Experiment 2 (duration trials), PIPR was induced using 100 and
      400 cd/m(2) full-field stimulus of increasing duration from 4 to 1000 ms (10
      steps). RESULTS: Results indicated that PIPR increased monotonically with
      increasing stimulus intensity. Full-field stimulation using blue light at 400
      cd/m(2) intensity induced significantly more sustained PIPR than central-field
      stimulation (P = 0.001). In addition, PIPR increased as the stimulus duration
      increased from 4 to 200 ms; however, no further increase in PIPR was observed
      when the duration increased from 400 to 1000 ms. CONCLUSIONS: Compared to
      existing central-field protocols, larger PIPR can be induced with a full-field
      stimulus with lower intensity and shorter duration, indicating that PIPR is a
      function of stimulus intensity, stimulus duration, and retinal area stimulated.
      The testing protocol can be refined with this new knowledge to target particular
      clinical populations.

PMID- 24925882
TI  - Reply: 99mTc-MAA-based dosimetry for liver cancer treated using 90Y-loaded
      microspheres: known proof of effectiveness.

PMID- 24925881
TI  - Pain at multiple body sites and health-related quality of life in older adults:
      results from the North Staffordshire Osteoarthritis Project.
AB  - OBJECTIVES: Number of pain sites (NPS) is a potentially important marker of
      health-related quality of life (HRQoL) but remains unexplored in older people.
      This cross-sectional study investigated whether, in older people including the
      oldest old, NPS was independently associated with poorer mental and physical
      HRQoL and if the association was moderated by age. METHODS: A postal
      questionnaire sent to a population sample of adults aged >=50 years in North
      Staffordshire, UK, included the 12-item Short Form Health Survey (SF-12) mental
      component summary (MCS) and physical component summary (PCS), a blank body pain
      manikin, socio-demographic, health behaviour and morbidity questions.
      Participants shaded sites of pain lasting >=1 day in the past 4 weeks on the
      manikin. OA consultation data were obtained for participants consenting to
      medical records review. RESULTS: A total of 13 986 individuals (adjusted response
      70.6%) completed a questionnaire, of which 12 408 provided complete pain data.
      The median NPS reported was 4 [interquartile range (IQR) 0-8]. General linear
      models showed that an increasing NPS was significantly associated with poorer MCS
      (beta = -0.43, 95% CI -0.46, -0.40) and PCS (beta = -0.87, 95% CI -0.90, -0.84).
      Adjustment for covariates attenuated the associations but they remained
      significant ( MCS: beta = -0.28, 95% CI -0.31, -0.24; PCS: beta = -0.63, 95% CI 
      0.66, -0.59). The association between NPS and MCS or PCS was moderated by age,
      but the strongest associations were not in the oldest old. CONCLUSION: NPS
      appears to be a potentially modifiable target for improving physical and mental
      HRQoL in older people. Future analyses should investigate the influence of NPS on
      HRQoL over time in older people.

PMID- 24925883
TI  - 99mTc-MAA-based dosimetry for liver cancer treated using 90Y-loaded microspheres:
      known proof of effectiveness.

PMID- 24925884
TI  - Correlation between in vivo 18F-FDG PET and immunohistochemical markers of
      glucose uptake and metabolism in pheochromocytoma and paraganglioma.
AB  - Pheochromocytomas and paragangliomas (PPGLs) can be localized by (18)F-FDG PET.
      The uptake is particularly high in tumors with an underlying succinate
      dehydrogenase (SDH) mutation. SDHx-related PPGLs are characterized by compromised
      oxidative phosphorylation and a pseudohypoxic response, which mediates an
      increase in aerobic glycolysis, also known as the Warburg effect. The aim of this
      study was to explore the hypothesis that increased uptake of (18)F-FDG in SDHx
      related PPGLs is reflective of increased glycolytic activity and is correlated
      with expression of different proteins involved in glucose uptake and metabolism
      through the glycolytic pathway. METHODS: Twenty-seven PPGLs collected from
      patients with hereditary mutations in SDHB (n = 2), SDHD (n = 3), RET (n = 5),
      neurofibromatosis 1 (n = 1), and myc-associated factor X (n = 1) and sporadic
      patients (n = 15) were investigated. Preoperative (18)F-FDG PET/CT studies were
      analyzed; mean and maximum standardized uptake values (SUVs) in manually drawn
      regions of interest were calculated. The expression of proteins involved in
      glucose uptake (glucose transporters types 1 and 3 [GLUT-1 and -3,
      respectively]), phosphorylation (hexokinases 1, 2, and 3 [HK-1, -2, and -3,
      respectively]), glycolysis (monocarboxylate transporter type 4 [MCT-4]), and
      angiogenesis (vascular endothelial growth factor [VEGF], CD34) were examined in
      paraffin-embedded tumor tissues using immunohistochemical staining with
      peroxidase-catalyzed polymerization of diaminobenzidine as a read-out. The
      expression was correlated with corresponding SUVs. RESULTS: Both maximum and mean
      SUVs for SDHx-related tumors were significantly higher than those for sporadic
      and other hereditary tumors (P < 0.01). The expression of HK-2 and HK-3 was
      significantly higher in SDHx-related PPGLs than in sporadic PPGLs (P = 0.022 and
      0.025, respectively). The expression of HK-2 and VEGF was significantly higher in
      SDHx-related PPGLs than in other hereditary PPGLs (P = 0.039 and 0.008,
      respectively). No statistical differences in the expression were observed for
      GLUT-1, GLUT-3, and MCT-4. The percentage anti-CD 34 staining and mean vessel
      perimeter were significantly higher in SDHx-related PPGLs than in sporadic tumors
      (P = 0.050 and 0.010, respectively). Mean SUVs significantly correlated with the
      expression of HK-2 (P = 0.027), HK-3 (P = 0.013), VEGF (P = 0.049), and MCT-4 (P
      = 0.020). CONCLUSION: The activation of aerobic glycolysis in SDHx-related PPGLs
      is associated with increased (18)F-FDG accumulation due to accelerated glucose
      phosphorylation by hexokinases rather than increased expression of glucose
      transporters.

PMID- 24925886
TI  - Radial dose distributions from protons of therapeutic energies calculated with
      Geant4-DNA.
AB  - Models based on the amorphous track structure approximation have been successful
      in predicting the biological effects of heavy charged particles. Development of
      such models remains an active area of research that includes applications to
      hadrontherapy. In such models, the radial distribution of the dose deposited by
      delta electrons and directly by the particle is the main characteristic of track
      structure. We calculated these distributions with Geant4-DNA Monte Carlo code for
      protons in the energy range from 10 to 100 MeV. These results were approximated
      by a simple formula that combines the well-known inverse square distance
      dependence with two factors that eliminate the divergence of the radial dose
      integral at both small and large distances. A clear physical interpretation is
      given to the asymptotic behaviour of the radial dose distribution resulting from
      these two factors. The proposed formula agrees with the Monte Carlo data within
      10% for radial distances of up to 10 MUm, which corresponds to a dose range
      covering over eight orders of magnitude. Differences between our results and
      those of previously published analytical models are discussed. 

PMID- 24925885
TI  - Individual-reader diagnostic performance and between-reader agreement in
      assessment of subjects with Parkinsonian syndrome or dementia using 123I
      ioflupane injection (DaTscan) imaging.
AB  - Establishing an early, accurate diagnosis is fundamental for appropriate clinical
      management of patients with movement disorders or dementia. Ioflupane (123)I
      Injection (DaTscan, (123)I-ioflupane) is an important adjunct to support the
      clinical diagnosis. Understanding individual-reader diagnostic performance of
      (123)I-ioflupane in a variety of clinical scenarios is essential. METHODS:
      Sensitivity, specificity, interreader, and intrareader data from 5 multicenter
      clinical studies were reviewed. The different study designs offered an assortment
      of variables to assess the effects on the diagnostic performance of (123)I
      ioflupane: on-site versus 3-5 blinded image readers, number of image evaluations,
      early/uncertain versus late/confirmed clinical diagnosis as reference standard,
      and subjects with movement disorders versus dementia. RESULTS: Eight hundred
      eighteen subjects had individual-reader efficacy data available for analysis. In
      general, sensitivity and specificity were high and comparable between on-site
      versus blinded independent readers. In subjects with dementia, when the clinical
      diagnosis was made at month 12 versus baseline, specificity improved from 77.4%
      91.2% to 81.6%-95.0%. In subjects with movement disorders, this effect was
      observed to an even greater extent, when diagnostic performance using month-18
      diagnosis as a reference standard (sensitivity, 67.0%-73.7%; specificity, 75.0%
      83.3%) was compared versus month-36 diagnosis (77.5%-80.3% and 90.3%-96.8%,
      respectively). Diagnostic performance was similar in subjects with dementia
      (74.4%-89.9% and 77.4%-95.0%, respectively) and subjects with movement disorders
      (67.0%-97.9% and 71.4%-98.4%, respectively). In most of the comparisons, between
      reader agreement was very good (almost perfect), with kappa ranging from 0.81 to
      1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded
      readers. CONCLUSION: Individual-reader diagnostic performance, as assessed by
      measuring sensitivity and specificity of (123)I-ioflupane to detect the presence
      or absence of striatal dopaminergic deficit, using the clinical diagnosis as a
      reference standard, was high in subjects with either movement disorders or
      dementia and was similar in on-site readers versus blinded analyses. Between- and
      within-reader agreements were very good (almost perfect). Longer follow-up
      between imaging and clinical diagnosis improved the diagnostic accuracy, most
      likely due to improvement in the clinical diagnosis reference standard, rather
      than changes in reader accuracy.

PMID- 24925887
TI  - Tests for equivalence of two survival functions: Alternative to the tests under
      proportional hazards.
AB  - For either the equivalence trial or the non-inferiority trial with survivor
      outcomes from two treatment groups, the most popular testing procedure is the
      extension (e.g., Wellek, A log-rank test for equivalence of two survivor
      functions, Biometrics, 1993; 49: 877-881) of log-rank based test under
      proportional hazards model. We show that the actual type I error rate for the
      popular procedure of Wellek is higher than the intended nominal rate when
      survival responses from two treatment arms satisfy the proportional odds survival
      model. When the true model is proportional odds survival model, we show that the
      hypothesis of equivalence of two survival functions can be formulated as a
      statistical hypothesis involving only the survival odds ratio parameter. We
      further show that our new equivalence test, formulation, and related procedures
      are applicable even in the presence of additional covariates beyond treatment
      arms, and the associated equivalence test procedures have correct type I error
      rates under the proportional hazards model as well as the proportional odds
      survival model. These results show that use of our test will be a safer
      statistical practice for equivalence trials of survival responses than the
      commonly used log-rank based tests.

PMID- 24925888
TI  - Diminished role for dopamine D1 receptors in cocaine addiction?

PMID- 24925889
TI  - Blunted dopamine release as a biomarker for vulnerability for substance use
      disorders.

PMID- 24925890
TI  - Association of genes involved in calcium and potassium pathways with opioid
      dependence.

PMID- 24925891
TI  - Digital anthropomorphic phantoms of non-rigid human respiratory and voluntary
      body motion for investigating motion correction in emission imaging.
AB  - The development of methods for correcting patient motion in emission tomography
      has been receiving increased attention. Often the performance of these methods is
      evaluated through simulations using digital anthropomorphic phantoms, such as the
      commonly used extended cardiac torso (XCAT) phantom, which models both
      respiratory and cardiac motion based on human studies. However, non-rigid body
      motion, which is frequently seen in clinical studies, is not present in the
      standard XCAT phantom. In addition, respiratory motion in the standard phantom is
      limited to a single generic trend. In this work, to obtain a more realistic
      representation of motion, we developed a series of individual-specific XCAT
      phantoms, modeling non-rigid respiratory and non-rigid body motions derived from
      the magnetic resonance imaging (MRI) acquisitions of volunteers. Acquisitions
      were performed in the sagittal orientation using the Navigator methodology.
      Baseline (no motion) acquisitions at end-expiration were obtained at the
      beginning of each imaging session for each volunteer. For the body motion
      studies, MRI was again acquired only at end-expiration for five body motion poses
      (shoulder stretch, shoulder twist, lateral bend, side roll, and axial slide). For
      the respiratory motion studies, an MRI was acquired during free/regular
      breathing. The magnetic resonance slices were then retrospectively sorted into 14
      amplitude-binned respiratory states, end-expiration, end-inspiration, six
      intermediary states during inspiration, and six during expiration using the
      recorded Navigator signal. XCAT phantoms were then generated based on these MRI
      data by interactive alignment of the organ contours of the XCAT with the MRI
      slices using a graphical user interface. Thus far we have created five body
      motion and five respiratory motion XCAT phantoms from the MRI acquisitions of six
      healthy volunteers (three males and three females). Non-rigid motion exhibited by
      the volunteers was reflected in both respiratory and body motion phantoms with a
      varying extent and character for each individual. In addition to these phantoms,
      we recorded the position of markers placed on the chest of the volunteers for the
      body motion studies, which could be used as external motion measurement. Using
      these phantoms and external motion data, investigators will be able to test their
      motion correction approaches for realistic motion obtained from different
      individuals. The non-uniform rational B-spline data and the parameter files for
      these phantoms are freely available for downloading and can be used with the XCAT
      license. 

PMID- 24925892
TI  - Can we distinguish pneumonia from wheezy diseases in tachypnoeic children under
      low-resource conditions? A prospective observational study in four Indian
      hospitals.
AB  - BACKGROUND: Acute respiratory infections are the commonest cause of mortality and
      morbidity in children worldwide. A quarter of all deaths occur in India alone. In
      order to reduce this disease burden, there is a need for better diagnostic
      criteria, particularly ones allowing early detection of high-risk children.
      METHODS: We enrolled 516 under 5 year olds, in four Indian hospitals, who met WHO
      age-dependent tachypnoea criteria for pneumonia at presentation. Patients
      underwent a protocolised examination assessing 29 items, including history,
      examination, O2 saturation, plus scores for chest X-ray, auscultation and
      conscious level. Treatment was determined by the emergency room (ER) physician.
      All children were reviewed at day 4 by a paediatrician and placed into four
      diagnostic categories: pneumonia, wheezy disease, mixed and non-respiratory.
      RESULTS: The majority had wheezy diseases (42.8%). The remainder had pneumonia
      (35.9%), mixed disease (18.6%) and non-respiratory (2.7%). Best diagnostic
      predictors for wheezy disease were (auscultation/previous similar episodes) and
      for pneumonia (auscultation/CXR score). Mortality was 1.6%. Best disease severity
      predictors were conscious level, weight/age z score and respiratory/pulse rates.
      INTERPRETATION: Current tachypnoea-based algorithms significantly overdiagnose
      pneumonia in children and underdiagnose wheezy diseases. Diagnostic accuracy can
      be improved by various combinations of clinical variables, but the best single
      diagnostic predictor is auscultation. Simple criteria can also be defined that
      reliably detect which tachypnoeic children are at high risk of death or
      deterioration. Management plans based on these protocols could reduce unnecessary
      antibiotic use, improve the management of wheezy diseases and reduce mortality by
      earlier identification of high-risk children.

PMID- 24925893
TI  - Knowledge and skills retention following Emergency Triage, Assessment and
      Treatment plus Admission course for final year medical students in Rwanda: a
      longitudinal cohort study.
AB  - AIM: To determine whether, after the Emergency Triage, Assessment and Treatment
      plus Admission (ETAT+) course, a comprehensive paediatric life support course,
      final year medical undergraduates in Rwanda would achieve a high level of
      knowledge and practical skills and if these were retained. To guide further
      course development, student feedback was obtained. METHODS: Longitudinal cohort
      study of knowledge and skills of all final year medical undergraduates at the
      University of Rwanda in academic year 2011-2012 who attended a 5-day ETAT+
      course. Students completed a precourse knowledge test. Knowledge and clinical
      skills assessments, using standardised marking, were performed immediately
      postcourse and 3-9 months later. Feedback was obtained using printed
      questionnaires. RESULTS: 84 students attended the course and re-evaluation.
      Knowledge test showed a significant improvement, from median 47% to 71% correct
      answers (p<0.001). For two clinical skills scenarios, 98% passed both scenarios,
      37% after a retake, 2% failed both scenarios. Three to nine months later,
      students were re-evaluated, median score for knowledge test 67%, not
      significantly different from postcourse (p>0.1). For clinical skills, 74% passed,
      with 32% requiring a retake, 8% failed after retake, 18% failed both scenarios, a
      significant deterioration (p<0.0001). CONCLUSIONS: Students performed well on
      knowledge and skills immediately after a comprehensive ETAT+ course. Knowledge
      was maintained 3-9 months later. Clinical skills, which require detailed
      sequential steps, declined, but most were able to perform them satisfactorily
      after feedback. The course was highly valued, but several short courses and more
      practical teaching were advocated.

PMID- 24925894
TI  - Systematic review and meta-analysis of behavioral interventions for fecal
      incontinence with constipation.
AB  - BACKGROUND: Multiple treatments exist for fecal incontinence. However, the
      relative and additive influence of commonly used behavioral approaches remains
      unclear. OBJECTIVE: We conducted a systematic review of randomized controlled
      trials to synthesize the effects of behavioral treatment of fecal incontinence
      with constipation in children aged 4-18 years. Mixed treatment comparisons (MTCs)
      and random effects models were used to analyze outcomes. Risk of bias and quality
      of evidence were rated. RESULTS: Although 10 studies were identified for MTCs,
      results did not yield reliable or valid estimates. Four studies were retained for
      random effects pooled outcome analysis. Results indicated that behavioral
      intervention was more effective than control conditions for author-defined
      success and soiling frequency. CONCLUSION: Although evidence supports behavioral
      treatments for fecal incontinence with constipation in children, available
      evidence is limited. More and higher-quality trials are needed to better
      understand the relative effects of different treatments, including behavioral
      strategies.

PMID- 24925895
TI  - Surgical resident evaluations of portable laparoscopic box trainers incorporated
      into a simulation-based minimally invasive surgery curriculum.
AB  - INTRODUCTION: Box trainers have been shown to be an effective tool for teaching
      laparoscopic skills; however, residents are challenged to find practice time.
      Portable trainers theoretically allow for extended hands on practice out of the
      hospital. We aimed to report resident experience with laparoscopic home box
      trainers. METHODS: Over 2 years, all residents rotating through a minimally
      invasive service were given a portable trainer and access to a surgical
      simulation lab for practice. Each trainer contained a collapsible frame, a webcam
      with USB port, trocars, and laparoscopic instruments (needle driver, shears,
      Maryland and straight dissecting graspers) as well as Fundamentals of
      Laparoscopic Surgery skills testing materials. Residents were asked to log hours,
      usages, and their experience anonymously. RESULTS: Twenty-three residents
      received a portable trainer. Fifty percent of the participants found the trainer
      useful or very useful, 25% said it was not useful, and 25% did not access the
      trainer. Those that used the trainer during their rotation did so 3.1 +/- 3.0
      times for 2.9 +/- 3.0 hours/week. After completing their rotation, 5 of 12
      residents used their trainer for an average of 10.2 +/- 9.4 hours. Forty-two
      percent of the responders liked the accessibility of the home box trainers, while
      25% criticized the camera-computer interface. CONCLUSIONS: Portable box trainers
      are useful and can effectively supplement a laboratory-based surgical simulation
      curriculum; however, personal possession of a portable simulator does not result
      in voluntarily long-term practice.

PMID- 24925896
TI  - An emerging understanding of the Janus face of the human microbiome: enhancement
      versus impairment of cancer therapy.

PMID- 24925880
TI  - The prevalence and incidence of epiretinal membranes in eyes with inactive
      extramacular CMV retinitis.
AB  - PURPOSE: To determine the prevalence and incidence of epiretinal membranes (ERM)
      in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients
      with acquired immune deficiency syndrome (AIDS). METHODS: A case-control report
      from a longitudinal multicenter observational study by the Studies of the Ocular
      Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients
      with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular
      opportunistic infection (OOI) were studied. Stereoscopic views of the posterior
      pole from fundus photographs were assessed at baseline and year 5 visits for the
      presence of macular ERM. Generalized estimating equations (GEE) logistic
      regression was used to compare the prevalence and 5-year incidence of ERM in eyes
      with and without CMV retinitis at enrollment. Crude and adjusted logistic
      regression was performed adjusting for possible confounders. Main outcome
      measures included the prevalence, incidence, estimated prevalence, and incidence
      odds ratios. RESULTS: The prevalence of ERM at enrollment was 14.8% (53/357) in
      eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence
      of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4%
      (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval,
      CI) for prevalence was 9.8 (5.5-17.5) (P < 0.01). The crude OR (95% CI) for
      incidence was 9.4 (3.2-27.9) (P < 0.01). CONCLUSIONS: A history of extramacular
      CMV retinitis is associated with increased prevalence and incidence of ERM
      formation compared to what is seen in eyes without ocular opportunistic
      infections in AIDS patients.

PMID- 24925897
TI  - Prevalence of Trichomonas vaginalis, Mycoplasma genitalium and Ureaplasma
      urealyticum in men with urethritis attending an urban sexual health clinic.
AB  - We conducted a study to determine the prevalence of Trichomonas vaginalis (TV),
      Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) in men with
      urethritis, attending an urban sexual health clinic, in order to inform screening
      and treatment policies. Men attending an urban sexual health clinic between June
      2011 and January 2012 were evaluated. Urine samples were collected from men with
      urethritis and tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC)
      and TV using transcription-mediated amplification and for MG and UU using
      polymerase chain reaction. Eighty-three samples were analysed. The prevalence of
      CT was 33.7% (28/83), GC was 16.8% (14/83), TV was 3.6% (3/83), MG was 12.0%
      (10/83) and UU was 4.8% (4/83). Fifteen men had recurrent urethritis. Of these,
      three were found to have had TV, five to have had MG and none to have had UU, at
      initial presentation. Given the prevalence of MG in this study, there is an
      urgent need for further larger studies looking at optimal treatment regimens and
      screening strategies in urethritis. 

PMID- 24925898
TI  - Therapeutic efficacy of a H4 receptor antagonist in humans: a milestone in
      histamine research.

PMID- 24925899
TI  - Spectral fluence of neutrons generated by radiotherapeutic linacs.
AB  - Spectral fluences of neutrons generated in the heads of the radiotherapeutic
      linacs Varian Clinac 2100 C/D and Siemens ARTISTE were measured by means of the
      Bonner spheres spectrometer whose active detector of thermal neutrons was
      replaced by an activation detector, i.e. a tablet made of pure manganese.
      Measurements with different collimator settings reveal an interesting dependence
      of neutron fluence on the area defined by the collimator jaws. The determined
      neutron spectral fluences were used to derive ambient dose equivalent rate along
      the treatment coach. To clarify at which components of the linac neutrons are
      mainly created, the measurements were complemented with MCNPX calculations based
      on a realistic model of the Varian Clinac. 

PMID- 24925900
TI  - Cytogenetic studies for a group of people living in Japan 1 year after the
      Fukushima nuclear accident.
AB  - In order to understand the potential health effect of radiation from Fukushima
      nuclear disaster, a group of people living in Japan during and after the accident
      were investigated 1 y after the accident. The venous blood samples were extracted
      in tune from 156 tested persons living in Tokyo and Niigata with average age of
      42.4 +/- 10.2 y old as well as 87 controls living in Beijing with similar age and
      sex proportion. Conventional chromosome culture and cytochalasin B micronucleus
      methods were applied. The unstable chromosome aberrations of 200 cells and
      micronuclei (MN) and micronuclei cells (MNC) of 1000 binucleated lymphocytes were
      analysed for each examined subject. The results showed that the frequencies +/-
      SE (*100) of the dicentrics plus rings were 0.17 +/- 0.024% and 0.13 +/- 0.028%
      in the tested and control populations (p > 0.05), respectively. The frequencies
      of the extra acentrics were 0.21 +/- 0.026% and 0.06 +/- 0.018% in the tested and
      control groups (p < 0.01), respectively. The total chromosomal aberration
      frequencies of the tested and control groups were 0.40 +/- 0.036% and 0.20 +/-
      0.034% (p < 0.01), respectively. The MN and MNC frequencies of the tested group
      were 29.25 +/- 3.96 0/00 and 23.85 +/- 4.23 0/00, and 25.30 +/- 6.45 0/00 and
      21.56 +/- 3.99 0/00 for control group (p < 0.01). With the exception of
      dicentrics, there were significant differences (p < 0.01) between two groups in
      frequencies of chromosome aberration and MN. Generally, 1 y after the Fukushima
      nuclear accident, the dicentric frequencies had not increased in the 156 persons
      investigated in this study. The increase in chromatid aberrations, chromosomal
      acentrics and MN was induced but could not be directly linked to radiation
      exposures, as an excess of dicentric frequency is linked. However, the observed
      higher frequency of chromosomal alterations might be related to exposure to the
      low doses of ionising in this cohort. Consequently, it is recommended to assess
      the long-term health effects in this population.

PMID- 24925901
TI  - Protein biomarkers for enhancement of radiation dose and injury assessment in
      nonhuman primate total-body irradiation model.
AB  - Development and validation of early-response radiation injury biomarkers are
      critical for effective triage and medical management of irradiated individuals.
      Plasma protein and haematological profiles were evaluated using multivariate
      linear-regression analysis to provide dose-response calibration curves for photon
      radiation dose assessment in 30 rhesus macaques total-body-irradiated to 1-8.5 Gy
      with (60)Co gamma rays (0.55 Gy min(-1)). Equations for radiation dose received
      were established based on different combinations of protein biomarkers [i.e. C
      reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6) and Flt3
      Ligand (Flt3L)] at samples collection time-points 6 h, 1, 2, 3, 4 and 7 d post
      total-body irradiation. Dynamic changes in the levels of CRP, SAA, IL-6 and Flt3L
      may function as prognostic indicators of the time course and severity of acute
      radiation sickness (ARS). The combination of protein biomarkers provides greater
      accuracy for early radiation assessment than any one biomarker alone. 

PMID- 24925902
TI  - Influence of clouds on the cosmic radiation dose rate on aircraft.
AB  - Flight missions were made in Brazilian territory in 2009 and 2011 with the aim of
      measuring the cosmic radiation dose rate incident on aircraft in the South
      Atlantic Magnetic Anomaly and to compare it with Monte Carlo simulations. During
      one of these flights, small fluctuations were observed in the vicinity of the
      aircraft with formation of Cumulonimbus clouds. Motivated by these observations,
      in this work, the authors investigated the relationship between the presence of
      clouds and the neutron flux and dose rate incident on aircraft using
      computational simulation. The Monte Carlo simulations were made using the MCNPX
      and Geant4 codes, considering the incident proton flux at the top of the
      atmosphere and its propagation and neutron production through several vertically
      arranged slabs, which were modelled according to the ISO specifications. 

PMID- 24925903
TI  - Alterations in the cerebellar (Phospho)proteome of a cyclic guanosine
      monophosphate (cGMP)-dependent protein kinase knockout mouse.
AB  - The cyclic nucleotide cyclic guanosine monophosphate (cGMP) plays an important
      role in learning and memory, but its signaling mechanisms in the mammalian brain
      are not fully understood. Using mass-spectrometry-based proteomics, we evaluated
      how the cerebellum adapts its (phospho)proteome in a knockout mouse model of cGMP
      dependent protein kinase type I (cGKI). Our data reveal that a small subset of
      proteins in the cerebellum (~3% of the quantified proteins) became substantially
      differentially expressed in the absence of cGKI. More changes were observed at
      the phosphoproteome level, with hundreds of sites being differentially
      phosphorylated between wild-type and knockout cerebellum. Most of these
      phosphorylated sites do not represent known cGKI substrates. An integrative
      computational network analysis of the data indicated that the differentially
      expressed proteins and proteins harboring differentially phosphorylated sites
      largely belong to a tight network in the Purkinje cells of the cerebellum
      involving important cGMP/cAMP signaling nodes (e.g. PDE5 and PKARIIbeta) and
      Ca(2+) signaling (e.g. SERCA3). In this way, removal of cGKI could be linked to
      impaired cerebellar long-term depression at Purkinje cell synapses. In addition,
      we were able to identify a set of novel putative (phospho)proteins to be
      considered in this network. Overall, our data improve our understanding of
      cerebellar cGKI signaling and suggest novel players in cGKI-regulated synaptic
      plasticity. 

PMID- 24925904
TI  - Maternal mindfulness and anxiety during pregnancy affect infants' neural
      responses to sounds.
AB  - Maternal anxiety during pregnancy has been consistently shown to negatively
      affect offspring neurodevelopmental outcomes. However, little is known about the
      impact of positive maternal traits/states during pregnancy on the offspring. The
      present study was aimed at investigating the effects of the mother's mindfulness
      and anxiety during pregnancy on the infant's neurocognitive functioning at 9
      months of age. Mothers reported mindfulness using the Freiburg Mindfulness
      Inventory and anxiety using the Symptom Checklist (SCL-90) at +/- 20.7 weeks of
      gestation. Event-related brain potentials (ERPs) were measured from 79 infants in
      an auditory oddball paradigm designed to measure auditory attention-a key aspect
      of early neurocognitive functioning. For the ERP responses elicited by standard
      sounds, higher maternal mindfulness was associated with lower N250 amplitudes (P
      < 0.01, eta(2) = 0.097), whereas higher maternal anxiety was associated with
      higher N250 amplitudes (P < 0.05, eta(2) = 0.057). Maternal mindfulness was also
      positively associated with the P150 amplitudes (P < 0.01, eta(2) = 0.130). These
      results suggest that infants prenatally exposed to higher levels of maternal
      mindfulness devote fewer attentional resources to frequently occurring irrelevant
      sounds. The results show that positive traits and experiences of the mother
      during pregnancy may also affect the unborn child. Emphasizing the beneficial
      effects of a positive psychological state during pregnancy may promote healthy
      behavior in pregnant women.

PMID- 24925905
TI  - A computational framework for heparan sulfate sequencing using high-resolution
      tandem mass spectra.
AB  - Heparan sulfate (HS) is a linear polysaccharide expressed on cell surfaces, in
      extracellular matrices and cellular granules in metazoan cells. Through non
      covalent binding to growth factors, morphogens, chemokines, and other protein
      families, HS is involved in all multicellular physiological activities. Its
      biological activities depend on the fine structures of its protein-binding
      domains, the determination of which remains a daunting task. Methods have
      advanced to the point that mass spectra with information-rich product ions may be
      produced on purified HS saccharides. However, the interpretation of these complex
      product ion patterns has emerged as the bottleneck to the dissemination of these
      HS sequencing methods. To solve this problem, we designed HS-SEQ, the first
      comprehensive algorithm for HS de novo sequencing using high-resolution tandem
      mass spectra. We tested HS-SEQ using negative electron transfer dissociation
      (NETD) tandem mass spectra generated from a set of pure synthetic saccharide
      standards with diverse sulfation patterns. The results showed that HS-SEQ rapidly
      and accurately determined the correct HS structures from large candidate pools. 

PMID- 24925907
TI  - Comparison of susceptibility of cystic-fibrosis-related and non-cystic-fibrosis
      related Pseudomonas aeruginosa to chlorine-based disinfecting solutions:
      implications for infection prevention and ward disinfection.
AB  - Multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from cystic fibrosis
      (CF) sputum was shown to be more tolerant to the most commonly used chlorine
      based disinfecting agent in the UK, with approximately 7 out of 10 isolates
      surviving a residual free chlorine (RFC) concentration of 500 p.p.m., when
      compared with antibiotic-sensitive invasive P. aeruginosa from a non-CF blood
      culture source, where 8 out of 10 isolates were killed at a RFC concentration of
      100 p.p.m. All CF isolates were killed at 1000 p.p.m. chlorine. Additional
      studies were performed to examine factors that influenced the concentration of
      RFC from chlorine-based (sodium dichloroisocyanurate) disinfecting agents in
      contact with CF sputum and their components (bacterial cells, glycocalyx) to
      assess the reduction of the bactericidal activity of such disinfecting agents.
      Pseudomonas glycocalyx had a greater inhibitory effect of chlorine deactivation
      than bacterial cells. Calibration curves demonstrated the relative deactivating
      capacity on RFC from clinical soils, in the order pus>CF sputum>wound discharge
      fluid/synovial fluid>ascites fluid>bile, where quantitatively each 1 % (w/v) CF
      sputum reduced the RFC by 43 p.p.m. Sublethal stressing of P. aeruginosa with
      chlorine resulted in lowered susceptibility to colistin (P = 0.0326) but not to
      meropenem, tobramycin or ciprofloxacin. In conclusion, heavy contamination of
      healthcare fomites with CF sputum containing MDR P. aeruginosa may result in
      exhaustion of RFC, and this, combined with an increased resistance to chlorine
      with such strains, may lead to their survival and increased antibiotic resistance
      in such environments. CF infection prevention strategies in such scenarios should
      therefore target interventions with increased concentrations of chlorine to
      ensure the eradication of MDR P. aeruginosa from the CF healthcare environment. 

PMID- 24925906
TI  - Identification of a novel neurotrophic factor from primary retinal Muller cells
      using stable isotope labeling by amino acids in cell culture (SILAC).
AB  - Retinal Muller glial cells (RMGs) have a primary role in maintaining the
      homeostasis of the retina. In pathological situations, RMGs execute protective
      and regenerative effects, but they can also contribute to neurodegeneration. It
      has recently been recognized that cultured primary RMGs secrete pro-survival
      factors for retinal neurons for up to 2 weeks in culture, but this ability is
      lost when RMGs are cultivated for longer durations. In our study, we investigated
      RMG supernatants for novel neuroprotective factors using a quantitative proteomic
      approach. Stable isotope labeling by amino acids in cell culture (SILAC) was used
      on primary porcine RMGs. Supernatants of RMGs cultivated for 2 weeks were
      compared with supernatants from cells that had already lost their protective
      capacity. Using this approach, we detected established neurotrophic factors such
      as transferrin, osteopontin, and leukemia inhibitory factor and identified C-X-C
      motif chemokine 10 (CXCL10) as a novel candidate neuroprotective factor. All
      factors prolonged photoreceptor survival in vitro. Ex vivo treatment of retinal
      explants with leukemia inhibitory factor or CXCL10 demonstrated a neuroprotective
      effect on photoreceptors. Western blots on CXCL10- and leukemia inhibitory factor
      stimulated explanted retina and photoreceptor lysates indicated activation of pro
      survival signal transducer and activator of transcription signaling and B-cell
      lymphoma pathways. These findings suggest that CXCL10 contributes to the
      supportive potential of RMGs toward retinal neurons. 

PMID- 24925908
TI  - The Bentall procedure with a biological valved conduit: substitute options and
      techniques.
AB  - As originally described by Bentall and De Bono, aortic root replacement with
      reimplantation of the coronary arteries using a composite valved conduit
      represents the gold standard intervention in patients with aneurysmal disease or
      dissection involving the aortic root. Over the last decade, the number of Bentall
      procedures performed using biological valved conduit has dramatically expanded
      mainly due to the increased incidence of aortic disease in the aging population.
      Here, we sought to describe the commercially available biological composite
      grafts and the techniques that, to the best of our knowledge, are most frequently
      used in this setting. 

PMID- 24925909
TI  - Neurodevelopment. Parasympathetic neurons originate from nerve-associated
      peripheral glial progenitors.
AB  - The peripheral autonomic nervous system reaches far throughout the body and
      includes neurons of diverse functions, such as sympathetic and parasympathetic.
      We show that the parasympathetic system in mice--including trunk ganglia and the
      cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia--arise
      from glial cells in nerves, not neural crest cells. The parasympathetic fate is
      induced in nerve-associated Schwann cell precursors at distal peripheral sites.
      We used multicolor Cre-reporter lineage tracing to show that most of these
      neurons arise from bi-potent progenitors that generate both glia and neurons.
      This nerve origin places cellular elements for generating parasympathetic neurons
      in diverse tissues and organs, which may enable wiring of the developing
      parasympathetic nervous system.

PMID- 24925911
TI  - Quantum computations on a topologically encoded qubit.
AB  - The construction of a quantum computer remains a fundamental scientific and
      technological challenge because of the influence of unavoidable noise. Quantum
      states and operations can be protected from errors through the use of protocols
      for quantum computing with faulty components. We present a quantum error
      correcting code in which one qubit is encoded in entangled states distributed
      over seven trapped-ion qubits. The code can detect one bit flip error, one phase
      flip error, or a combined error of both, regardless on which of the qubits they
      occur. We applied sequences of gate operations on the encoded qubit to explore
      its computational capabilities. This seven-qubit code represents a fully
      functional instance of a topologically encoded qubit, or color code, and opens a
      route toward fault-tolerant quantum computing. 

PMID- 24925910
TI  - Feedback control of chromosome separation by a midzone Aurora B gradient.
AB  - Accurate chromosome segregation during mitosis requires the physical separation
      of sister chromatids before nuclear envelope reassembly (NER). However, how these
      two processes are coordinated remains unknown. Here, we identified a conserved
      feedback control mechanism that delays chromosome decondensation and NER in
      response to incomplete chromosome separation during anaphase. A midzone
      associated Aurora B gradient was found to monitor chromosome position along the
      division axis and to prevent premature chromosome decondensation by retaining
      Condensin I. PP1/PP2A phosphatases counteracted this gradient and promoted
      chromosome decondensation and NER. Thus, an Aurora B gradient appears to mediate
      a surveillance mechanism that prevents chromosome decondensation and NER until
      effective separation of sister chromatids is achieved. This allows the correction
      and reintegration of lagging chromosomes in the main nuclei before completion of
      NER. 

PMID- 24925912
TI  - Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors.
AB  - Neural crest cells migrate extensively and give rise to most of the peripheral
      nervous system, including sympathetic, parasympathetic, enteric, and dorsal root
      ganglia. We studied how parasympathetic ganglia form close to visceral organs and
      what their precursors are. We find that many cranial nerve-associated crest cells
      coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b)
      together with markers of Schwann cell precursors. Some give rise to Schwann cells
      after down-regulation of PHOX2b. Others form parasympathetic ganglia after being
      guided to the site of ganglion formation by the nerves that carry preganglionic
      fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell
      precursors are the source of parasympathetic neurons during normal development. 

PMID- 24925913
TI  - Superconductivity. Fermi arcs in a doped pseudospin-1/2 Heisenberg
      antiferromagnet.
AB  - High-temperature superconductivity in cuprates arises from an electronic state
      that remains poorly understood. We report the observation of a related electronic
      state in a noncuprate material, strontium iridate (Sr2IrO4), in which the
      distinct cuprate fermiology is largely reproduced. Upon surface electron doping
      through in situ deposition of alkali-metal atoms, angle-resolved photoemission
      spectra of Sr2IrO4 display disconnected segments of zero-energy states, known as
      Fermi arcs, and a gap as large as 80 millielectron volts. Its evolution toward a
      normal metal phase with a closed Fermi surface as a function of doping and
      temperature parallels that in the cuprates. Our result suggests that Sr2IrO4 is a
      useful model system for comparison to the cuprates. 

PMID- 24925914
TI  - Single-cell RNA-seq highlights intratumoral heterogeneity in primary
      glioblastoma.
AB  - Human cancers are complex ecosystems composed of cells with distinct phenotypes,
      genotypes, and epigenetic states, but current models do not adequately reflect
      tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to
      profile 430 cells from five primary glioblastomas, which we found to be
      inherently variable in their expression of diverse transcriptional programs
      related to oncogenic signaling, proliferation, complement/immune response, and
      hypoxia. We also observed a continuum of stemness-related expression states that
      enabled us to identify putative regulators of stemness in vivo. Finally, we show
      that established glioblastoma subtype classifiers are variably expressed across
      individual cells within a tumor and demonstrate the potential prognostic
      implications of such intratumoral heterogeneity. Thus, we reveal previously
      unappreciated heterogeneity in diverse regulatory programs central to
      glioblastoma biology, prognosis, and therapy. 

PMID- 24925915
TI  - Lipids in cell biology: how can we understand them better?
AB  - Lipids are a major class of biological molecules and play many key roles in
      different processes. The diversity of lipids is on the same order of magnitude as
      that of proteins: cells express tens of thousands of different lipids and
      hundreds of proteins to regulate their metabolism and transport. Despite their
      clear importance and essential functions, lipids have not been as well studied as
      proteins. We discuss here some of the reasons why it has been challenging to
      study lipids and outline technological developments that are allowing us to begin
      lifting lipids out of their "Cinderella" status. We focus on recent advances in
      lipid identification, visualization, and investigation of their biophysics and
      perturbations and suggest that the field has sufficiently advanced to encourage
      broader investigation into these intriguing molecules.

PMID- 24925916
TI  - CFTR: cystic fibrosis and beyond.
AB  - Cystic fibrosis (CF) remains the most common fatal hereditary lung disease. The
      discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene
      25 years ago set the stage for: 1) unravelling the molecular and cellular basis
      of CF lung disease; 2) the generation of animal models to study in vivo
      pathogenesis; and 3) the development of mutation-specific therapies that are now
      becoming available for a subgroup of patients with CF. This article highlights
      major advances in our understanding of how CFTR dysfunction causes chronic mucus
      obstruction, neutrophilic inflammation and bacterial infection in CF airways.
      Furthermore, we focus on recent breakthroughs and remaining challenges of novel
      therapies targeting the basic CF defect, and discuss the next steps to be taken
      to make disease-modifying therapies available to a larger group of patients with
      CF, including those carrying the most common mutation DeltaF508-CFTR. Finally, we
      will summarise emerging evidence indicating that acquired CFTR dysfunction may be
      implicated in the pathogenesis of chronic obstructive pulmonary disease,
      suggesting that lessons learned from CF may be applicable to common airway
      diseases associated with mucus plugging. 

PMID- 24925917
TI  - Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further
      analysis.

PMID- 24925918
TI  - Reliance on end-expiratory wedge pressure leads to misclassification of pulmonary
      hypertension.
AB  - Current guidelines recommend measurement of pulmonary artery wedge pressure
      (PAWP) at end-expiration. However, this recommendation is not universally
      followed and may not be physiologically appropriate. We investigated the
      performance of end-expiratory PAWP in the evaluation of precapillary pulmonary
      hypertension patients. 329 spontaneously breathing patients undergoing right
      heart catheterisation were retrospectively classified as having a precapillary,
      post-capillary or mixed phenotype based on standardised clinical criteria.
      Tracings were reviewed to compare end-expiratory PAWP with PAWP averaged
      throughout the respiratory cycle; these values were correlated with the clinical
      classifications. Predictors of large respirophasic variation in PAWP were
      determined. Elevated end-expiratory PAWP (>15 mmHg) occurred in 29% of subjects
      with precapillary phenotype. There were no differences in demographics or
      clinical history between those with elevated and normal end-expiratory PAWP.
      Those with elevated end-expiratory PAWP had greater right atrial pressure and
      respirophasic PAWP variation. Among all subjects, the magnitude of respirophasic
      variation in PAWP was positively correlated with body mass index and
      respirophasic variation in left ventricular end-diastolic pressure. A significant
      proportion of precapillary pulmonary hypertension patients have end-expiratory
      PAWP >15 mmHg. Spontaneous positive end-expiratory intrathoracic pressure may
      contribute; in those cases, PAWP averaged throughout respiration may be a more
      accurate measurement. 

PMID- 24925920
TI  - Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic
      review.
AB  - We conducted a meta-analysis of randomised trials to evaluate the efficacy and
      safety of inhaled antibiotics in patients with stable non-cystic fibrosis (CF)
      bronchiectasis. We searched the Cochrane Airways Group Register of Trials from
      inception until March 2014. 12 trials with 1264 adult patients were included, of
      which five were unpublished studies. Eight trials on 590 patients contributed
      data to the meta-analysis. Amikacin, aztreonam, ciprofloxacin, gentamicin,
      colistin or tobramycin were used for 4 weeks to 12 months. Inhaled antibiotics
      were more effective than placebo or symptomatic treatment in reducing sputum
      bacterial load (five trials; weighted mean difference -2.65 log10 CFU . g(-1),
      95% CI -4.38- -0.92 log10 CFU . g(-1)), eradicating the bacteria from sputum (six
      trials; risk ratio 4.2, 95% CI 1.66-10.64) and reducing the risk of acute
      exacerbations (five trials; risk ratio 0.72, 95% CI 0.55-0.94). Bronchospasm
      occurred in 10% of patients treated with inhaled antibiotics compared with 2.3%
      in the control group (seven trials; risk ratio 2.96, 95% CI 1.30-6.73), but the
      two groups had the same withdrawal rate due to adverse events (12.2%). Inhaled
      antibiotics may provide an effective suppressive antibiotic therapy with an
      acceptable safety profile in adult patients with stable non-CF bronchiectasis and
      chronic bronchial infection.

PMID- 24925921
TI  - Interleukin-17 cytokine signalling in patients with asthma.
AB  - Asthma remains a global health problem and, therefore, more effective
      pharmacotherapy is needed. This is particularly true for chronic and severe
      asthma. In these clinical phenotypes, chronic inflammation involving neutrophils
      is likely to play a pathogenic role, making it interesting to target cytokine
      signalling involved in the accumulation of neutrophils. Therefore, it is of
      interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A,
      perhaps also IL-17F, controls neutrophil accumulation, mucus secretion,
      macrophage mobilisation and smooth muscle reactivity in various experimental
      airway models. However, much less is known about the involvement of signalling
      via IL-17 cytokines in humans with asthma. Existing evidence suggests that these
      cytokines are released from several types of immune cells in asthma and, for IL
      17A, there is a local increase associated with disease severity, with the
      mobilisation of neutrophils and smooth muscle cells locally in the airways. Even
      though the causative role of IL-17 cytokines remains unclear, there is potential
      for clinical utility in targeting IL-17A specifically in patients with moderate
      to-severe asthma and high reversibility. There is a need for new and well-powered
      clinical investigations of signalling via IL-17 cytokines in this clinical
      phenotype. 

PMID- 24925923
TI  - Surgical and nonsurgical approaches to small-size nonsmall cell lung cancer.
AB  - Lobectomy and systematic nodal dissection are still the standard for small-size
      (<3 cm) nonsmall cell lung cancer. There is growing interest in more parenchyma
      sparing surgery, so-called sublobar resections (wedge resection or
      segmentectomy). Indeed, nonrandomised trials suggest that a segmentectomy may
      result in local control rates that are similar to lobectomy. Nonsurgical
      approaches, such as stereotactic ablative radiotherapy, consistently result in
      local control rates of ~ 90% and survival rates that are comparable to lobectomy.
      Therefore, we are moving towards an era in which several therapeutic
      possibilities are available, that are probably equivalent from an oncological
      point of view. Further trials are needed to define the optimal therapy for
      individual patients.

PMID- 24925924
TI  - COPD detected with screening: impact on patient management and prognosis.
AB  - It is uncertain whether screening of older persons for chronic obstructive
      pulmonary disease (COPD) is worthwhile because the effects on patient management
      and prognosis are unknown. We aimed to assess the short-term consequences of
      detecting COPD in frail elderly subjects with dyspnoea, considering pulmonary
      drug use, hospitalisations and all-cause mortality. Community-dwelling frail
      elderly subjects, aged 65 years and older, with dyspnoea, participating in a
      screening study on COPD and heart failure were included. Final diagnoses were
      assigned by an expert panel based on all data from the screening strategy,
      including spirometry. Follow-up data were collected from the general
      practitioners. Of the 386 patients, 84 (21.8%) were received a new diagnosis of
      COPD. Overall, changes in pulmonary drug prescription during 6 months of follow
      up were infrequent (n = 53, 13.7%; among new cases of COPD, 15 (17.9%) out of
      84). Of all participants, 25.9% were hospitalised in the first year of follow-up,
      with the highest rate in patients with newly detected COPD (32.1%). Many new
      cases of COPD could be detected by screening frail elderly subjects with
      dyspnoea, but the impact on patient management seems limited. Our study
      underlines the importance of obtaining follow-up data to assess the true impact
      of a (screen-detected) diagnosis of COPD on patient management and outcome. 

PMID- 24925922
TI  - Pathophysiology of human ventilatory control.
AB  - We review the substantial recent progress made in understanding the underlying
      mechanisms controlling breathing and the applicability of these findings to
      selected human diseases. Emphasis is placed on the sites of central respiratory
      rhythm and pattern generation as well as newly described functions of the carotid
      chemoreceptors, the integrative nature of the central chemoreceptors, and the
      interaction between peripheral and central chemoreception. Recent findings that
      support critical contributions from cortical central command and muscle afferent
      feedback to exercise hyperpnoea are also reviewed. These basic principles, and
      the evidence supporting chemoreceptor and ventilatory control system plasticity
      during and following constant and intermittent hypoxaemia and stagnant hypoxia,
      are applied to: 1) the pathogenesis, consequences and treatment of obstructive
      sleep apnoea; and 2) exercise hyperpnoea and its control and limitations with
      ageing, chronic obstructive pulmonary disease and congestive heart failure. 

PMID- 24925925
TI  - Detecting concerted demographic response across community assemblages using
      hierarchical approximate Bayesian computation.
AB  - Methods that integrate population-level sampling from multiple taxa into a single
      community-level analysis are an essential addition to the comparative
      phylogeographic toolkit. Detecting how species within communities have
      demographically tracked each other in space and time is important for
      understanding the effects of future climate and landscape changes and the
      resulting acceleration of extinctions, biological invasions, and potential surges
      in adaptive evolution. Here, we present a statistical framework for such an
      analysis based on hierarchical approximate Bayesian computation (hABC) with the
      goal of detecting concerted demographic histories across an ecological
      assemblage. Our method combines population genetic data sets from multiple taxa
      into a single analysis to estimate: 1) the proportion of a community sample that
      demographically expanded in a temporally clustered pulse and 2) when the pulse
      occurred. To validate the accuracy and utility of this new approach, we use
      simulation cross-validation experiments and subsequently analyze an empirical
      data set of 32 avian populations from Australia that are hypothesized to have
      expanded from smaller refugia populations in the late Pleistocene. The method can
      accommodate data set heterogeneity such as variability in effective population
      size, mutation rates, and sample sizes across species and exploits the
      statistical strength from the simultaneous analysis of multiple species. This
      hABC framework used in a multitaxa demographic context can increase our
      understanding of the impact of historical climate change by determining what
      proportion of the community responded in concert or independently and can be used
      with a wide variety of comparative phylogeographic data sets as biota-wide DNA
      barcoding data sets accumulate. 

PMID- 24925919
TI  - Integrated care pathways for airway diseases (AIRWAYS-ICPs).
AB  - The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is
      to launch a collaboration to develop multi-sectoral care pathways for chronic
      respiratory diseases in European countries and regions. AIRWAYS-ICPs has
      strategic relevance to the European Union Health Strategy and will add value to
      existing public health knowledge by: 1) proposing a common framework of care
      pathways for chronic respiratory diseases, which will facilitate comparability
      and trans-national initiatives; 2) informing cost-effective policy development,
      strengthening in particular those on smoking and environmental exposure; 3)
      aiding risk stratification in chronic disease patients, using a common strategy;
      4) having a significant impact on the health of citizens in the short term
      (reduction of morbidity, improvement of education in children and of work in
      adults) and in the long-term (healthy ageing); 5) proposing a common simulation
      tool to assist physicians; and 6) ultimately reducing the healthcare burden
      (emergency visits, avoidable hospitalisations, disability and costs) while
      improving quality of life. In the longer term, the incidence of disease may be
      reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5
      of the Action Plan B3 of the European Innovation Partnership on Active and
      Healthy Ageing. All stakeholders are involved (health and social care, patients,
      and policy makers).

PMID- 24925927
TI  - Women's experiences of polycystic ovary syndrome diagnosis.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and complex endocrine
      condition affecting women across the lifespan. Diagnosis experience may impact on
      physical and emotional well-being and engagement with evidence-based management
      and treatment. OBJECTIVE: To explore the perceived experience of PCOS diagnosis,
      prior to development of an evidence-based guideline for PCOS assessment and
      management. METHODS: Cross-sectional study, involving devised questionnaires
      completed by a national, community-based sample of 210 women with a previous
      medical diagnosis of PCOS, aged 18-45 years, in Australia. Main outcome measures
      included time to diagnosis, number of health professionals seen and information
      provision. RESULTS: Mean age (+/- standard deviation) was 31 (+/-5.8) years and
      median body mass index (interquartile range) was 30 (12) kg/m(2). For 24% of
      women, PCOS diagnosis took >2 years and 39% saw three or more health
      professionals before diagnosis was made. The majority (60%) reported they were
      not given or referred to information sources at time of diagnosis, 20% reported
      receiving information and 20% were given information but felt it was inadequate.
      Of those who reported provision of information at diagnosis, 62% felt
      dissatisfied with or indifferent to information provided about PCOS, 79% reported
      being provided with information about lifestyle management, 89% reported being
      provided with information about medical therapy, 83% about long-term
      complications and 95% about potential infertility. CONCLUSIONS: PCOS diagnosis
      experience can be lengthy, involve many health professionals and leave unmet
      information needs. The current findings inform the need for evidence-based PCOS
      resources for women and health professionals.

PMID- 24925926
TI  - Genome-wide transcript profiling reveals the coevolution of plastid gene
      sequences and transcript processing pathways in the fucoxanthin dinoflagellate
      Karlodinium veneficum.
AB  - Plastids utilize a complex gene expression machinery, which has coevolved with
      the underlying genome sequence. Relatively, little is known about the genome-wide
      evolution of transcript processing in algal plastids that have undergone complex
      endosymbiotic events. We present the first genome-wide study of transcript
      processing in a plastid acquired through serial endosymbiosis, in the fucoxanthin
      containing dinoflagellate Karlodinium veneficum. The fucoxanthin dinoflagellate
      plastid has an extremely divergent genome and utilizes two unusual transcript
      processing pathways, 3'-poly(U) tail addition and sequence editing, which were
      acquired following the serial endosymbiosis event. We demonstrate that poly(U)
      addition and sequence editing are widespread features across the Karl. veneficum
      plastid transcriptome, whereas other dinoflagellate plastid lineages that have
      arisen through independent serial endosymbiosis events do not utilize either RNA
      processing pathway. These pathways constrain the effects of divergent sequence
      evolution in fucoxanthin plastids, for example by correcting mutations in the
      genomic sequence that would otherwise be deleterious, and are specifically
      associated with transcripts that encode functional plastid proteins over
      transcripts of recently generated pseudogenes. These pathways may have
      additionally facilitated divergent evolution within the Karl. veneficum plastid.
      Transcript editing, for example, has contributed to the evolution of a novel C
      terminal sequence extension on the Karl. veneficum AtpA protein. We furthermore
      provide the first complete sequence of an episomal minicircle in a fucoxanthin
      dinoflagellate plastid, which contains the dnaK gene, and gives rise to
      polyuridylylated and edited transcripts. Our results indicate that RNA processing
      in fucoxanthin dinoflagellate plastids is evolutionarily dynamic, coevolving with
      the underlying genome sequence. 

PMID- 24925928
TI  - Profile of French general practitioners providing opportunistic primary
      preventive care--an observational cross-sectional multicentre study.
AB  - BACKGROUND: Preventive services provided opportunistically by GPs are
      insufficient. Reasons are most often gathered through GPs' self-reports, rather
      than through independent observation. OBJECTIVE: To assess with passive
      observers, the degree to which French GPs opportunistically perform primary
      preventive care during routine consultation. METHODS: Observational cross
      sectional multicentre ancillary study of the French ECOGEN study. The study
      period extended from 28 November 2011 to 30 April 2012. The inclusion criteria
      were patients seen by GPs at surgery and home consultations in non-randomized pre
      determined half-day blocks per week. The non-inclusion criteria were patient's
      refusal and consultations initially focused on primary prevention in response to
      patient's request (ancillary study's specific criterion). Using passive
      observers, data were collected based on the second version of International
      Classification of Primary Care. Preventive consultations were defined if at least
      one problem/diagnosis was considered by consensus as definitely related to
      primary prevention. For each one of the 128 participating GPs, aggregation of
      data was performed from all his/her consultations. Determinants of the proportion
      of preventive consultations per GP were assessed by multivariate linear
      regression. RESULTS: Considering 19003 consultations, the median proportion of
      preventive consultations per GP was 14.9% (range: 0-78.3%). It decreased with
      increased proportion of patients aged 18 or less (P = 0.006), with increased
      proportion of home visits (P = 0.008) and with increased proportion of
      consultations lasting under 10 minutes (P = 0.02). None of the GPs' personal
      characteristics were significantly associated. CONCLUSION: Primary preventive
      care activity was related to the characteristics of GPs' patients and practice
      organizational markers and not to GPs' personal characteristics.

PMID- 24925929
TI  - Balancing the risks and benefits of parenteral nutrition for preterm infants: can
      we define the optimal composition?
AB  - Nutrient intakes in preterm infants are frequently inadequate and are associated
      with worse neuro-developmental outcome. Preterm infants take time to establish
      enteral intakes, and parenteral nutrition (PN) is now an integral component of
      care. Despite this, the evidence base for PN intakes is extremely limited. There
      remains uncertainty over safe initial and maximum amounts of macronutrients, and
      the optimal amino acid and lipid composition. Studies have tended to focus on
      short-term growth measures and there are few studies with long-term follow-up.
      There may be a tradeoff between improving cognitive outcomes while minimising
      metabolic harm that means determining the optimal regimen will require long-term
      follow-up. Given the importance of appropriate nutrition for long-term metabolic
      and cognitive health, and the associated healthcare costs, optimising the
      composition of PN deserves to be seen as a research priority in neonatal
      medicine. 

PMID- 24925930
TI  - The family physician of the future.

PMID- 24925932
TI  - Family physicians can champion sport-related concussion management: it's about
      time.

PMID- 24925933
TI  - Importance of education in managing type 2 diabetes during Ramadan.

PMID- 24925934
TI  - Pandemic of idiopathic multimorbidity.

PMID- 24925937
TI  - NACI update on pertussis vaccination in pregnancy.

PMID- 24925938
TI  - Response.

PMID- 24925939
TI  - Response to letters about vitamin B12.

PMID- 24925940
TI  - Powerful tool with manageable risks.

PMID- 24925941
TI  - Office management of mild head injury in children and adolescents.
AB  - OBJECTIVE: To provide family physicians with updated, practical, evidence-based
      information about mild head injury (MHI) and concussion in the pediatric
      population. SOURCES OF INFORMATION: MEDLINE (1950 to February 2013), the Cochrane
      Database of Systematic Reviews (2005 to 2013), the Cochrane Central Register of
      Controlled Trials (2005 to 2013), and DARE (2005 to 2013) were searched using
      terms relevant to concussion and head trauma. Guidelines, position statements,
      articles, and original research relevant to MHI were selected. MAIN MESSAGE:
      Trauma is the main cause of death in children older than 1 year of age, and
      within this group head trauma is the leading cause of disability and death. Nine
      percent of reported athletic injuries in high school students involve MHI. Family
      physicians need to take a focused history, perform physical and neurologic
      examinations, use standardized evaluation instruments (Glasgow Coma Scale; the
      Sport Concussion Assessment Tool, version 3; the child version of the Sport
      Concussion Assessment Tool; and the Balance Error Scoring System), instruct
      parents how to monitor their children, decide when caregivers are not an
      appropriately responsible resource, follow up with patients promptly, guide a
      safe return to play and to learning, and decide when neuropsychological testing
      for longer-term follow-up is required. CONCLUSION: A thorough history, physical
      and neurologic assessment, the use of validated tools to provide an objective
      framework, and periodic follow-up are the basis of family physician management of
      pediatric MHI.

PMID- 24925942
TI  - Approach to patients with unexplained multimorbidity with sensitivities.
AB  - OBJECTIVE: To explore the underlying causation of unexplained multimorbidity with
      sensitivities and to discuss the management of patients who present with this
      perplexing condition. SOURCES OF INFORMATION: Medical and scientific literature
      was used from MEDLINE (PubMed), several books, toxicology and allergy journals,
      conference proceedings, government publications, and environmental health
      periodicals. MAIN MESSAGE: Multimorbidity with sensitivities has become an
      increasingly common and confusing primary care dilemma. Escalating numbers of
      debilitated individuals are now presenting to family physicians and specialists
      with multisystem health complaints, including sensitivities and fatigue, with no
      obvious causation, a paucity of laboratory findings, and a lack of
      straightforward solutions. In the recent scientific literature, there is
      discussion of sensitivity-related illness, an immune-mediated disorder that
      frequently manifests with multisystem symptoms, commonly including sensitivities
      and fatigue. This condition appears to be originally caused by adverse
      environmental exposures and toxicant bioaccumulation-an increasingly prevalent
      and well-documented problem in contemporary culture. CONCLUSION: Various toxic
      exposures and their bioaccumulation within the body frequently manifest as
      sensitivity-related illness. In clinical settings, patients with this disorder
      often present with otherwise unexplained multimorbidity and sensitivities. The
      health status of patients with this condition can be ameliorated by removing
      triggers (eg, scented products), optimizing biochemistry, removing further
      sources of toxicant exposures, and eliminating the internal dose of persistent
      toxicants.

PMID- 24925943
TI  - Using nitrofurantoin while breastfeeding a newborn.
AB  - QUESTION: My patient has a urinary tract infection and is currently
      breastfeeding. Her son is only 3 weeks old. Is nitrofurantoin a safe antibiotic
      for treatment? ANSWER: The use of nitrofurantoin in breastfeeding mothers is
      generally safe, as only small amounts transfer into the breast milk. Despite the
      lack of documented reports, there is a risk of hemolytic anemia in all newborns
      exposed to nitrofurantoin owing to their glutathione instability, especially in
      infants with glucose-6-phosphate dehydrogenase deficiency. Although some suggest
      that nitrofurantoin be avoided in infants younger than 1 month, studies have
      noted that glutathione stability might be established by the eighth day of life.
      In infants younger than 1 month, an alternative antibiotic might be preferred;
      however, if an alternative were not available, the use of nitrofurantoin would
      not be a reason to avoid breastfeeding. In any such case the suckling infant
      should be monitored by his or her physician.

PMID- 24925944
TI  - Treating to target: ready, fire, aim.

PMID- 24925945
TI  - Final days at home.

PMID- 24925946
TI  - Chronic urticaria as the first sign of sarcoidosis.

PMID- 24925947
TI  - Do family physicians, emergency department physicians, and pediatricians give
      consistent sport-related concussion management advice?
AB  - OBJECTIVE: To identify differences and gaps in recommendations to patients for
      the management of sport-related concussion among FPs, emergency department
      physicians (EDPs), and pediatricians. DESIGN: A self-administered, multiple
      choice survey was e-mailed to FPs, EDPs, and pediatricians. The survey had been
      assessed for content validity. SETTING: Two community teaching hospitals in the
      greater Toronto area in Ontario. PARTICIPANTS: Two hundred seventy physicians,
      including FPs, EDPs, and pediatricians, were invited to participate. MAIN OUTCOME
      MEASURES: Identification of sources of concussion management information,
      usefulness of concussion diagnosis strategies, and whether physicians use common
      terminology when explaining cognitive rest strategies to patients after sport
      related concussions. RESULTS: The response rate was 43.7%. Surveys were completed
      by 70 FPs, 23 EDPs, and 11 pediatricians. In total, 49% of FP, 52% of EDP, and
      27% of pediatrician respondents reported no knowledge of any consensus statements
      on concussion in sport, and 54% of FPs, 86% of EDPs, and 78% of pediatricians
      never used the Sport Concussion Assessment Tool, version 2. Only 49% of FPs, 57%
      of EDPs, and 36% of pediatricians always advised cognitive rest. CONCLUSION: This
      study identified large gaps in the knowledge of concussion guidelines and
      implementation of recommendations for treating patients with sport-related
      concussions. Although some physicians recommended physical and cognitive rest, a
      large proportion failed to consistently advise this strategy. Better knowledge
      transfer efforts should target all 3 groups of physicians.

PMID- 24925948
TI  - Victor Johnston, Murray Stalker, and the revival of general practice.

PMID- 24925949
TI  - More than just the T-shirt: reflections from first-time participants in global
      health service.

PMID- 24925950
TI  - Nelab alingary MD.

PMID- 24925952
TI  - W. Wayne Weston MD CCFP FCFP.

PMID- 24925954
TI  - Transdisciplinary understandings and training on research: successfully building
      research capacity in primary health care.

PMID- 24925955
TI  - Research and Education Foundation: celebrating 20 years of success: Supporting
      family medicine for a healthy Canada.

PMID- 24925957
TI  - Looking back and moving forward.

PMID- 24925960
TI  - Continuity in new models of care.

PMID- 24925965
TI  - Premature return to play and return to learn after a sport-related concussion:
      physician's chart review.
AB  - OBJECTIVE: To determine what proportion of patients experience an exacerbation of
      their symptoms as a result of premature return to play (RTP) and return to learn
      (RTL) following sport-related concussions. DESIGN: Retrospective study of
      electronic medical records from the office-based practice of one family and sport
      medicine physician who had systematically provided recommendations for cognitive
      and physical rest based on existing consensus recommendations. Two blinded
      authors independently reviewed each chart, which included Sport Concussion
      Assessment Tool (SCAT) and SCAT2 symptom self-report forms to determine whether
      an athlete had returned to play or learn prematurely. If there was a discrepancy
      between the 2 reviewers then a third author reviewed the charts. SETTING: A sport
      medicine and family practice in Ontario. The physician assessed sport-related
      concussions after self-referral or referral from other primary care physicians,
      teams, and schools. PARTICIPANTS: A total of 170 charts of 159 patients were
      assessed for sport-related concussion during a 5-year period (April 2006 to March
      2011). All participants were students who were participating in sports at the
      time of injury. There were 41 concussions in elementary students, 95 concussions
      in high school students, and 34 concussions in college or university students.
      MAIN OUTCOME MEASURES: Premature RTP and RTL were defined as chart records
      documenting the recurrence or worsening of symptoms that accompanied the
      patients' RTP or RTL. Measures were compared using the earliest available SCAT
      forms and self-reporting. RESULTS: In 43.5% of concussion cases, the patient
      returned to sport too soon and in 44.7% of concussion cases, the patient returned
      to school too soon. Patients with a history of previous concussion required more
      days of rest before being permitted to participate in any physical activity than
      those patients without a previous history of concussion. Elementary school
      students required fewer days of rest before being permitted to return to any
      physical activity compared with high school students and college or university
      students. CONCLUSION: Currently, physicians recommend restrictions on mental and
      physical activity following sport-related concussion. This is done without clear
      guidelines as to what cognitive rest entails for students. Further research is
      required to determine how to implement a management plan for student athletes to
      facilitate complete recovery after concussion.

PMID- 24925966
TI  - Educational role of nurse practitioners in a family practice centre: perspectives
      of learners and nurses.
AB  - OBJECTIVE: To examine the role of nurse practitioners (NPs) as educators of
      family medicine residents in order to better understand the interprofessional
      educational dynamics in a clinical teaching setting. DESIGN: A qualitative
      descriptive approach, using purposive sampling. SETTING: A family practice centre
      that is associated with an academic department of family medicine and is based in
      an urban area in southern Ontario. PARTICIPANTS: First-year (8 of 9) and second
      year (9 of 10) family medicine residents whose training program was based at the
      family practice centre, and all NPs (4 of 4) who worked at the centre. METHODS:
      Semistructured interviews were conducted, which were audiotaped and transcribed.
      An iterative approach was used for coding and analysis. Data management software
      guided organization and analysis of the data. MAIN FINDINGS: Four interconnected
      themes were identified: role clarification, professional identity formation,
      factors that enhance the educational role of NPs, and factors that limit the
      educational role of NPs. Although residents recognized NPs' value in team
      functioning and areas of specialized knowledge, they were unclear about NPs'
      scope of practice. Depending on residents' level of training, residents tended to
      respond differently to teaching by NPs. More of the senior residents believed
      they needed to think like physicians and preferred clinical teaching from
      physician teachers. Junior residents valued the step-by-step instructional
      approach used by NPs, and they had a decreased sense of vulnerability when being
      taught by NPs. Training in teaching skills was helpful for NPs. Barriers to
      providing optimal education included opportunity, time, and physician attitudes.
      CONCLUSION: The lack of an intentional orientation of family medicine residents
      to NPs' scope of practice and educational role can lead to difficulties in
      interprofessional education. More explicit recognition of the evolving
      professional identity of family medicine residents might decrease resistance to
      teaching by NPs and ensure that interprofessional teaching and learning
      strategies are effective. Faculty development opportunities for all educators are
      required to manage these issues, both to ensure teaching competencies and to
      reinforce positive interprofessional collaboration.

PMID- 24925967
TI  - Social isolation in older adults who are frequent users of primary care services.
AB  - OBJECTIVE: To describe older adults who are frequent users of primary care
      services and to explore associations between the number of primary care visits
      per year and multiple dimensions that define social isolation. DESIGN: Mailed,
      cross-sectional survey. SETTING: An urban academic primary care practice in
      Kingston, Ont. PARTICIPANTS: Forty patients aged 70 years and older who attended
      12 or more appointments in the previous year with residents, physicians, nurses,
      nurse practitioners, or registered practical nurses. MAIN OUTCOME MEASURES:
      Social isolation (size of close social network, loneliness, satisfaction with
      social participation, frequency of social participation), past and future need
      for health services related to social issues, and health and functional
      variables. RESULTS: The participants reported relatively low levels of
      loneliness, with a mean (SD) score of 4.1 (1.3) out of 9. Overall, 18.9% of
      participants reported having a small close social network, 45.9% of participants
      wanted to do more social activities, and 57.5% of participants were isolated
      according to at least 1 indicator. Some participants (23.1%) had received primary
      care services related to social issues, and most participants (54.5%) wanted
      these services in the future, including receiving information about other health
      services or community resources, or having discussions about loneliness,
      relationships, or social activities. Number of primary care visits was not
      associated with any of the 4 indicators of social isolation. CONCLUSION: Social
      isolation in older, frequent users of primary care services might be more common
      than previously thought, particularly the aspect of dissatisfaction with social
      participation. Expanded primary care services and referrals to other services
      might help to address this population's desires for services related to social
      issues. Future research could examine the social needs of older primary care
      attenders and the feasibility of providing related interventions in primary care
      settings.

PMID- 24925969
TI  - Stromal cell-derived factor-1alpha/C-X-C chemokine receptor type 4 axis promotes
      endothelial cell barrier integrity via phosphoinositide 3-kinase and Rac1
      activation.
AB  - OBJECTIVE: Although stromal cell-derived factor (SDF)-1alphais well known to
      modulate the mobilization of hematopoietic stem cells and endothelial progenitor
      cells, its effects on some pre-existing vascular functions remain unknown. We
      have investigated here the role of SDF-1alphasignaling in endothelial barrier
      function. APPROACH AND RESULTS: Treatment with SDF-1alpha elevated
      transendothelial electrical resistance and inhibited the dextran
      hyperpermeability elicited by thrombin in bovine aortic endothelial cells, both
      indicating an increase in endothelial barrier function. SDF-1alpha binds to 2
      receptors, C-X-C chemokine receptor types 4 and 7 (CXCR4 and CXCR7). Pretreatment
      with a CXCR4 antagonist or CXCR4 gene depletion by small interfering RNA (siRNA)
      eliminated SDF-1alpha-induced endothelial barrier enhancement. In contrast, CXCR7
      antagonist or CXCR7 gene depletion by siRNA did not influence SDF-1alpha-induced
      barrier enhancement. Pretreatment with a Gi-protein inhibitor, a phosphoinositide
      3-kinase (PI3K) inhibitor, or PI3K p110gammasubunit gene depletion by siRNA also
      inhibited SDF-1alpha-induced barrier enhancement significantly. Western blot
      analysis revealed that SDF-1alpha phosphorylated Akt(Ser473) in endothelial
      cells, suggesting PI3K activation. Immunostaining showed that treatment with SDF
      1alphaformed a cortical actin rim, which was accompanied by Rac1 activation. In
      vivo, SDF-1alphainhibited croton oil-induced vascular leakage indexed by dye
      extravasation, which is attenuated by a pretreatment with a CXCR4 antagonist.
      CONCLUSIONS: We have identified SDF-1alpha as a novel suppressor of endothelial
      permeability. Specifically, SDF-1alpha stimulates the CXCR4/PI3K/Rac1 signaling
      pathway and the subsequent cytoskeletal rearrangement.

PMID- 24925971
TI  - A common LPA null allele associates with lower lipoprotein(a) levels and coronary
      artery disease risk.
AB  - OBJECTIVE: Increased levels of lipoprotein(a) are a highly heritable risk factor
      for coronary artery disease (CAD). The genetic determinants of lipoprotein(a)
      levels are mainly because of genetic variation in the apolipoprotein(a) gene
      (LPA). We have tested the association of a relatively common null allele of LPA
      with lipoprotein(a) levels and CAD risk in a large case-control cohort. We have
      also examined how null allele genotyping complements apolipoprotein(a) isoform
      typing to refine the relationship between LPA isoform size and circulating
      lipoprotein(a) levels. APPROACH AND RESULTS: The LPA null allele (rs41272114) was
      genotyped in the PROCARDIS (Precocious Coronary Artery Disease) case-control
      cohort (4073 CAD cases and 4225 controls). Lipoprotein(a) levels were measured in
      909 CAD cases and 922 controls; apolipoprotein(a) isoform size was estimated
      using sodium dodecyl sulfate-agarose gel electrophoresis and a high-throughput
      quantitative polymerase chain reaction-based method. Null carriers are common
      (null allele frequency, 3%) and have significantly lower circulating
      lipoprotein(a) levels (P=2.1*10(-10)) and reduced CAD risk (odds ratio, 0.79
      [0.66-0.97]; P=0.023) compared with noncarriers. An additive allelic model of
      apolipoprotein(a) isoform size, refined by null allele genotype and quantitative
      polymerase chain reaction values, showed a sigmoid relationship with
      lipoprotein(a) levels, with baseline levels for longer isoform alleles and
      progressively higher levels of lipoprotein(a) for shorter isoform alleles.
      CONCLUSIONS: The LPA null allele (rs41272114) is associated with decreased
      circulating lipoprotein(a) levels and decreased CAD risk. Incorporating
      rs41272114 refined apolipoprotein(a) isoform size typing obtained by
      immunoblotting and quantitative polymerase chain reaction. A joint genomic and
      isoform analysis revealed details of the relationship between apolipoprotein(a)
      isoform size and circulating lipoprotein(a) level consistent with a threshold
      effect on lipoprotein secretion.

PMID- 24925970
TI  - Phosphodiesterase type 4 blockade prevents platelet-mediated neutrophil
      recruitment at the site of vascular injury.
AB  - OBJECTIVE: Platelet-neutrophil interactions play a key role in cardiovascular
      disease and inflammatory processes. Src family kinases mediate P-selectin
      glycoprotein ligand-1-Mac-1 cross talk necessary for firm platelet-neutrophil
      adhesion. Because Src family kinase activity can be regulated by cAMP-dependent
      pathways, in this work, we evaluated the role of phosphodiesterases in the
      signaling events that are required to sustain platelet-neutrophil interactions
      and neutrophil recruitment at the site of vascular injury. APPROACH AND RESULTS:
      In neutrophils exposed to P-selectin, selective phosphodiesterase 4 (PDE4)
      inhibition prevented Src family kinase-mediated phosphorylation of the proline
      rich tyrosine kinase 2 on Tyr579/Tyr580. The effects of PDE4 inhibition required
      protein kinase A, likely through protein kinase A-mediated activation of COOH
      terminal Src kinase, a major negative regulator of Src family kinases. PDE4, but
      not other phosphodiesterase inhibitors, reduced platelet-neutrophil conjugates as
      well as neutrophil firm adhesion on spread platelets under flow conditions. The
      effect of PDE4 inhibition on neutrophil adhesion was primarily mediated by
      downregulation of P-selectin-induced activation of Mac-1. In a murine model of
      endovascular injury, selective inhibition of PDE4 significantly reduced
      neutrophil recruitment at the site of vascular damage. CONCLUSIONS: This study
      identifies PDE4 as a central node in the signaling network that mediates platelet
      neutrophil adhesion and suggests that pharmacological inhibition of PDE4 may
      represent a novel therapeutic avenue for the treatment of cardiovascular disease.

PMID- 24925972
TI  - Receptor tyrosine kinases endocytosis in endothelium: biology and signaling.
AB  - Receptor tyrosine kinases are involved in regulation of key processes in
      endothelial biology, including proliferation, migration, and angiogenesis. It is
      now generally accepted that receptor tyrosine kinase signaling occurs
      intracellularly and on the plasma membrane, although many important details
      remain to be worked out. Endocytosis and subsequent intracellular trafficking
      spatiotemporally regulate receptor tyrosine kinase signaling, whereas signaling
      endosomes provide a platform for the compartmentalization of signaling events.
      This review summarizes recent advances in our understanding of endothelial
      receptor tyrosine kinase endocytosis and signaling using vascular endothelial
      growth factor receptor-2 as a paradigm. 

PMID- 24925973
TI  - Dietary intake of calcium and phosphorus and serum concentration in relation to
      the risk of coronary artery calcification in asymptomatic adults.
AB  - OBJECTIVE: The current data regarding the association between calcium and
      phosphorus and cardiovascular disease are lacking. The aim of this study was to
      explore whether dietary calcium and phosphorus intake and their serum levels are
      associated with the prevalence of coronary artery calcification (CAC) using
      cardiac computed tomography in asymptomatic participants without a history of
      chronic kidney disease or cardiovascular disease. APPROACH AND RESULTS: A cross
      sectional study was performed in 23 652 Korean participants (40.8+/-7.3 years,
      male 83.5%) without chronic kidney disease (estimated glomerular filtration
      rate>=60 mL/min per 1.73 m(2)) or clinically overt cardiovascular disease, who
      underwent cardiac computed tomographic estimation of CAC scores as part of a
      general health checkup in addition to completing a self-administered food
      frequency questionnaire. We assessed the relationship of dietary calcium and
      phosphorus intake and serum levels with CAC scores using both multivariate
      adjusted Tobit models and multinomial logistic regression models. Neither dietary
      calcium nor phosphorus intake was consistently associated with CAC scores.
      However, the serum calcium, phosphorus, and calcium-phosphorus product levels
      were significantly associated with the CAC score ratios. In multivariable
      adjusted models, the CAC score ratios (95% confidence intervals) comparing the
      highest quartiles of serum calcium, phosphorus, and calcium-phosphorus product
      levels to the lowest quartiles were 1.89 (1.36-2.64), 3.33 (2.55-4.35), and 3.98
      (3.00-5.28), respectively (P for trend <0.001). CONCLUSIONS: Elevated serum
      levels of calcium, phosphorus, and calcium-phosphorus product, but not dietary
      consumption, are associated with increased CAC scores. Our findings should be
      explored in further research.

PMID- 24925974
TI  - Lim domain binding 2: a key driver of transendothelial migration of leukocytes
      and atherosclerosis.
AB  - OBJECTIVE: Using a multi-tissue, genome-wide gene expression approach, we
      recently identified a gene module linked to the extent of human atherosclerosis.
      This atherosclerosis module was enriched with inherited risk for coronary and
      carotid artery disease (CAD) and overlapped with genes in the transendothelial
      migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes,
      the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in
      a CAD vascular wall regulatory gene network. Here, we used human genomics and
      atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and
      atherosclerosis. APPROACH AND RESULTS: mRNA profiles generated from blood
      macrophages in patients with CAD were used to infer transcription factor
      regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the
      effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most
      connected gene in a transcription factor regulatory network inferred from TEML
      and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100)
      mice, loss of Ldb2 increased atherosclerotic lesion size ~2-fold and decreased
      plaque stability. The exacerbated atherosclerosis was caused by increased TEML
      activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by
      ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In
      THP1 cells, migration was increased by overexpression and decreased by small
      interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was
      associated with the risk and extent of CAD across several cohorts. CONCLUSIONS:
      As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate
      to target CAD by inhibiting the overall activity of TEML.

PMID- 24925975
TI  - Targeting glycoprotein VI and the immunoreceptor tyrosine-based activation motif
      signaling pathway.
AB  - Coronary artery thrombosis and ischemic stroke are often initiated by the
      disruption of an atherosclerotic plaque and consequent intravascular platelet
      activation. Thus, antiplatelet drugs are central in the treatment and prevention
      of the initial, and subsequent, vascular events. However, novel pharmacological
      targets for platelet inhibition remain an important goal of cardiovascular
      research because of the negative effect of existing antiplatelet drugs on primary
      hemostasis. One promising target is the platelet collagen receptor glycoprotein
      VI. Blockade or antibody-mediated depletion of this receptor in circulating
      platelets is beneficial in experimental models of thrombosis and thrombo
      inflammatory diseases, such as stroke, without impairing hemostasis. In this
      review, we summarize the importance of glycoprotein VI and (hem)immunoreceptor
      tyrosine-based activation motif signaling in hemostasis, thrombosis, and thrombo
      inflammatory processes and discuss the targeting strategies currently under
      development for inhibiting glycoprotein VI and its signaling. 

PMID- 24925976
TI  - Nitric oxide prevents aortic neointimal hyperplasia by controlling macrophage
      polarization.
AB  - OBJECTIVE: Nitric oxide synthase 3 (NOS3) prevents neointima hyperplasia by still
      unknown mechanisms. To demonstrate the significance of endothelial nitric oxide
      in the polarization of infiltrated macrophages through the expression of matrix
      metalloproteinase (MMP)-13 in neointima formation. APPROACH AND RESULTS: After
      aortic endothelial denudation, NOS3 null mice show elevated neointima formation,
      detecting increased mobilization of LSK (lineage-negative [Lin]-stem-cell antigen
      1 [SCA1]+KIT+) progenitor cells, and high ratios of M1 (proinflammatory) to M2
      (resolving) macrophages, accompanied by high expression of interleukin-5,
      interleukin-6, MCP-1 (monocyte chemoattractant protein), VEGF (vascular
      endothelial growth factor), GM-CSF (granulocyte-macrophage colony stimulating
      factor), interleukin-1beta, and interferon-gamma. In conditional c-Myc knockout
      mice, in which M2 polarization is defective, denuded aortas showed extensive wall
      thickening as well. Conditioned medium from NOS3-deficient endothelium induced
      extensive repolarization of M2 macrophages to an M1 phenotype, and vascular
      smooth muscle cells proliferated and migrated faster in conditioned medium from
      M1 macrophages. Among the different proteins participating in cell migration, MMP
      13 was preferentially expressed by M1 macrophages. M1-mediated vascular smooth
      muscle cell migration was inhibited when macrophages were isolated from MMP-13
      deficient mice, whereas exogenous administration of MMP-13 to vascular smooth
      muscle cell fully restored migration. Excess vessel wall thickening in mice
      lacking NOS3 was partially reversed by simultaneous deletion of MMP-13,
      indicating that NOS3 prevents neointimal hyperplasia by preventing MMP-13
      activity. An excess of M1-polarized macrophages that coexpress MMP-13 was also
      detected in human carotid samples from endarterectomized patients. CONCLUSIONS:
      These findings indicate that at least M1 macrophage-mediated expression of MMP-13
      in NOS3 null mice induces neointima formation after vascular injury, suggesting
      that MMP-13 may represent a new promising target in vascular disease.

PMID- 24925977
TI  - Proinflammatory phenotype of perivascular adipocytes.
AB  - Perivascular adipose tissue (PVAT) directly abuts the lamina adventitia of
      conduit arteries and actively communicates with the vessel wall to regulate
      vascular function and inflammation. Mounting evidence suggests that the
      biological activities of PVAT are governed by perivascular adipocytes, a unique
      class of adipocyte with distinct molecular and phenotypic characteristics.
      Perivascular adipocytes surrounding human coronary arteries (pericoronary
      perivascular adipocytes) exhibit a reduced state of adipogenic differentiation
      and a heightened proinflammatory state, secreting <=50-fold higher levels of the
      proinflammatory cytokine monocyte chemoattractant peptide-1 compared with
      adipocytes from other regional depots. Thus, perivascular adipocytes may
      contribute to upregulated inflammation of PVAT observed in atherosclerotic human
      blood vessels. However, perivascular adipocytes also secrete anti-inflammatory
      molecules such as adiponectin, and elimination of PVAT in rodent models has been
      shown to augment vascular disease, suggesting that some amount of PVAT is
      required to maintain vascular homeostasis. Evidence in animal models and humans
      suggests that inflammation of PVAT may be modulated by environmental factors,
      such as high-fat diet and tobacco smoke, which are relevant to atherosclerosis.
      These findings suggest that the inflammatory phenotype of PVAT is diverse
      depending on species, anatomic location, and environmental factors and that these
      differences are fundamentally important in determining a pathogenic versus
      protective role of PVAT in vascular disease. Additional research into the
      mechanisms that regulate the inflammatory balance of perivascular adipocytes may
      yield new insight into, and treatment strategies for, cardiovascular disease. 

PMID- 24925978
TI  - Changing the paradigm for myoglobin: a novel link between lipids and myoglobin.
AB  - Myoglobin (Mb) is an oxygen-binding muscular hemeprotein regulated via Ca(2+)
      signaling pathways involving calcineurin (CN), with Mb increases attributed to
      hypoxia, exercise, and nitric oxide. Here, we show a link between lipid
      supplementation and increased Mb in skeletal muscle. C2C12 cells were cultured in
      normoxia or hypoxia with glucose or 5% lipid. Mb assays revealed that lipid
      cohorts had higher Mb than control cohorts in both normoxia and hypoxia, whereas
      Mb Western blots showed lipid cohorts having higher Mb than control cohorts
      exclusively under hypoxia. Normoxic cells were compared with soleus tissue from
      normoxic rats fed high-fat diets; whereas tissue sample cohorts showed no
      difference in CO-binding Mb, fat-fed rats showed increases in total Mb protein
      (similar to hypoxic cells), suggesting increases in modified Mb. Moreover, Mb
      increases did not parallel CN increases but did, however, parallel oxidative
      stress marker augmentation. Addition of antioxidant prevented Mb increases in
      lipid-supplemented normoxic cells and mitigated Mb increases in lipid
      supplemented hypoxic cells, suggesting a pathway for Mb regulation through redox
      signaling independent of CN. 

PMID- 24925979
TI  - Maximal exercise limitation in functionally overreached triathletes: role of
      cardiac adrenergic stimulation.
AB  - Functional overreaching (F-OR) induced by heavy load endurance training programs
      has been associated with reduced heart rate values both at rest and during
      exercise. Because this phenomenon may reflect an impairment of cardiac response,
      this research was conducted to test this hypothesis. Thirty-five experienced male
      triathletes were tested (11 control and 24 overload subjects) before overloading
      (Pre), immediately after overloading (Mid), and after a 2-wk taper period (Post).
      Physiological responses were assessed during an incremental cycling protocol to
      volitional exhaustion, including catecholamines release, oxygen uptake (Vo2),
      arteriovenous O2 difference, cardiac output (Q), and systolic (SBP) and diastolic
      blood pressure (DBP). Twelve subjects of the overload group developed signs of F
      OR at Mid (decreased performance with concomitant high perceived fatigue), while
      12 others did not [acute fatigue group (AF)]. Vo2max was reduced only in F-OR
      subjects at Mid. Lower Q and SBP values with greater arteriovenous O2 difference
      were reported in F-OR subjects at all exercising intensities, while no
      significant change was observed in the control and AF groups. A concomitant
      decrease in epinephrine excretion was reported only in the F-OR group. All values
      returned to baseline at Post. Following an overload endurance training program
      leading to F-OR, the cardiac response to exhaustive exercise is transiently
      impaired, possibly due to reduced epinephrine excretion. This finding is likely
      to explain the complex process of underperformance syndrome experienced by F-OR
      endurance athletes during heavy load programs. 

PMID- 24925980
TI  - Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva
      maneuver: comparison between healthy and autonomic dysfunction subjects.
AB  - The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF)
      to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is
      still controversial. We aimed to study the repercussion of autonomic failure (AF)
      on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial
      amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP
      and CBF velocity (CBFV) were measured continuously with Finapres and transcranial
      Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular
      resistance index (CVRi), critical closing pressure (CrCP), and resistance-area
      product (RAP) changes. Dynamic CA was derived from continuous estimates of
      autoregulatory index (ARI) [ARI(t)]. During phase II of VM, FAP subjects showed a
      more pronounced decrease in normalized CBFV (78 +/- 19 and 111 +/- 16%; P =
      0.002), ABP (78 +/- 19 and 124 +/- 12%; P = 0.0003), and RAP (67 +/- 17 and 89 +/
      17%; P = 0.019) compared with controls. CrCP and CVRi increased similarly in
      both groups during strain. ARI(t) showed a biphasic variation in controls with
      initial increase followed by a decrease during phase II but in FAP this response
      was blunted (5.4 +/- 3.0 and 2.0 +/- 2.9; P = 0.033). Our data suggest that
      dynamic cerebral autoregulatory response is a time-varying phenomena during VM
      and that it is disturbed by autonomic dysfunction. This study also emphasizes the
      fact that RAP + CrCP model allowed additional insights into understanding of
      cerebral hemodynamics, showing a higher vasodilatory response expressed by RAP in
      AF and an equal CrCP response in both groups during the increased intracranial
      and intrathoracic pressure, while classical CVRi paradoxically suggests a
      cerebral vasoconstriction. 

PMID- 24925981
TI  - Lung region and racing affect mechanical properties of equine pulmonary
      microvasculature.
AB  - Exercise-induced pulmonary hemorrhage is a performance-limiting condition of
      racehorses associated with severe pathology, including small pulmonary vein
      remodeling. Pathology is limited to caudodorsal (CD) lung. Mechanical properties
      of equine pulmonary microvasculature have not been studied. We hypothesized that
      regional differences in pulmonary artery and vein mechanical characteristics do
      not exist in control animals, and that racing and venous remodeling impact
      pulmonary vein mechanical properties in CD lung. Pulmonary arteries and veins
      [range of internal diameters 207-386 +/- 67 MUm (mean +/- SD)] were harvested
      from eight control and seven raced horses. With the use of wire myography, CD and
      cranioventral (CV) vessels were stretched in 10-MUm increments. Peak wall tension
      was plotted against changes in diameter (length). Length-tension data were
      compared between vessel type, lung region, and horse status (control and raced).
      Pulmonary veins are stiffer walled than arteries. CD pulmonary arteries are
      stiffer than CV arteries, whereas CV veins are stiffer than CD veins. Racing is
      associated with increased stiffness of CD pulmonary veins and, to a lesser
      extent, CV arteries. For example, at 305 MUm, tension in raced and control CD
      veins is 27.74 +/- 2.91 and 19.67 +/- 2.63 mN/mm (means +/- SE; P < 0.05,
      Bonferroni's multiple-comparisons test after two-way ANOVA), and 16.12 +/- 2.04
      and 15.07 +/- 2.47 mN/mm in raced and control CV arteries, respectively. This is
      the first report of an effect of region and/or exercise on mechanical
      characteristics of small pulmonary vessels. These findings may implicate
      pulmonary vein remodeling in exercise-induced pulmonary hemorrhage pathogenesis. 

PMID- 24925982
TI  - Lung arginase expression and activity is increased in cystic fibrosis mouse
      models.
AB  - The activity of arginase is increased in airway secretions of patients with
      cystic fibrosis (CF). Downstream products of arginase activity may contribute to
      CF lung disease. We hypothesized that pulmonary arginase expression and activity
      would be increased in mouse models of CF and disproportionally increased in CF
      mice with Pseudomonas aeruginosa pneumonia. Expression of arginase isoforms in
      lung tissue was quantified with reverse transcriptase-PCR in naive cystic
      fibrosis transmembrane conductance regulator (Cftr)-deficient mice and beta
      epithelial sodium channel-overexpressing [beta-ENaC-transgenic (Tg)] mice. An
      isolated lung stable isotope perfusion model was used to measure arginase
      activity in Cftr-deficient mice before and after intratracheal instillation of
      Pseudomonas aeruginosa. The expression of arginase-2 in lung was increased in
      adult Cftr-deficient animals and in newborn beta-ENaC-Tg. Arginase-1 lung
      expression was normal in Cftr-deficient and in newborn beta-ENaC-Tg mice, but was
      increased in beta-ENaC-Tg mice at age 1, 3, and 6 wk. Arginase activity was
      significantly higher in lung (5.0 +/- 0.7 vs. 3.2 +/- 0.3 nmol.(-1).h(-1), P =
      0.016) and airways (204.6 +/- 49.8 vs. 79.3 +/- 17.2 nmol.(-1).h(-1), P = 0.045)
      of naive Cftr-deficient mice compared with sex-matched wild-type littermate
      controls. Infection with Pseudomonas aeruginosa resulted in a far greater
      increase in lung arginase activity in Cftr-deficient mice (10-fold) than in wild
      type controls (6-fold) (P = 0.01). This is the first ex vivo characterization of
      arginase expression and activity in CF mouse lung and airways. Our data show that
      pulmonary arginase expression and activity is increased in CF mice, especially
      with Pseudomonas aeruginosa infections. 

PMID- 24925983
TI  - Buprenorphine detection in urine using liquid chromatography-high-resolution mass
      spectrometry: comparison with cloned enzyme donor immunoassay (ThermoFisher) and
      homogeneous enzyme immunoassay (immunalysis).
AB  - A sensitive liquid chromatographic-high-resolution mass spectrometric (LC-HR-MS)
      assay for buprenorphine and its urinary metabolites has been developed that
      requires minimal sample preparation. The results obtained have been compared with
      those given by (i) cloned enzyme donor immunoassay (CEDIA) and (ii) homogeneous
      enzyme immunoassay (HEIA) in the analysis of patient urines submitted for
      buprenorphine analysis. Centrifuged urine (100 uL) was diluted with internal
      standard solution (25 uL) + LC eluent (875 uL), and 50 uL of the prepared sample
      were analyzed (Accucore Phenyl-Hexyl column). MS detection was in alternating
      positive and negative mode using heated electrospray ionization (ThermoFisher Q
      Exactive). Intra- and inter-assay accuracy and precision were 104-128 and <11%,
      respectively, at 5 ug/L. Limits of detection were 1.3 ug/L (buprenorphine,
      norbuprenorphine and buprenorphine glucuronide) and 2.5 ug/L (norbuprenorphine
      glucuronide). Immunoassay sensitivity and selectivity were 97 and 100% (HEIA) and
      99 and 84% (CEDIA), respectively, compared with LC-HR-MS. In 120 patient urines,
      norbuprenorphine glucuronide was easily the most abundant analyte except when
      adulteration with buprenorphine had occurred. The median immunoreactive
      buprenorphine species present (unhydrolysed urine) were 7.5 and 13% for HEIA and
      CEDIA, respectively. However, codeine, dihydrocodeine, morphine and morphine-3
      glucuronide did not interfere in the HEIA assay. 

PMID- 24925984
TI  - Aripiprazole once-monthly for treatment of schizophrenia: double-blind,
      randomised, non-inferiority study.
AB  - BACKGROUND: Long-acting injectable formulations of antipsychotics are treatment
      alternatives to oral agents. AIMS: To assess the efficacy of aripiprazole once
      monthly compared with oral aripiprazole for maintenance treatment of
      schizophrenia. METHOD: A 38-week, double-blind, active-controlled, non
      inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg,
      oral aripiprazole (10-30 mg/day) or aripiprazole once-monthly 50 mg (a dose below
      the therapeutic threshold for assay sensitivity). ( TRIAL REGISTRATION:
      clinicaltrials.gov, NCT00706654.) RESULTS: A total of 1118 patients were
      screened, and 662 responders to oral aripiprazole were randomised. Kaplan-Meier
      estimated impending relapse rates at week 26 were 7.12% for aripiprazole once
      monthly 400 mg and 7.76% for oral aripiprazole. This difference (-0.64%, 95% CI 
      5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments
      were superior to aripiprazole once-monthly 50 mg (21.80%, P < or = 0.001).
      CONCLUSIONS: Aripiprazole once-monthly 400 mg was non-inferior to oral
      aripiprazole, and the reduction in Kaplan-Meier estimated impending relapse rate
      at week 26 was statistically significant v. aripiprazole once-monthly 50 mg.

PMID- 24925985
TI  - Gains in employment status following antidepressant medication or cognitive
      therapy for depression.
AB  - BACKGROUND: Depression can adversely affect employment status. AIMS: To examine
      whether there is a relative advantage of cognitive therapy or antidepressant
      medication in improving employment status following treatment, using data from a
      previously reported trial. METHOD: Random assignment to cognitive therapy (n =
      48) or the selective serotonin reuptake inhibitor paroxetine (n = 93) for 4
      months; treatment responders were followed for up to 24 months. Differential
      effects of treatment on employment status were examined. RESULTS: At the end of
      28 months, cognitive therapy led to higher rates of full-time employment (88.9%)
      than did antidepressant medication among treatment responders (70.8%), chi(2) 1 =
      5.78, P = 0.02, odds ratio (OR) = 5.66, 95% CI 1.16-27.69. In the shorter-term,
      the main effect of treatment on employment status was not significant following
      acute treatment (chi(2) 1 = 1.74, P = 0.19, OR = 1.77, 95% CI 0.75-4.17);
      however, we observed a site*treatment interaction (chi(2) 1 = 6.87, P = 0.009)
      whereby cognitive therapy led to a higher rate of full-time employment at one
      site but not at the other. CONCLUSIONS: Cognitive therapy may produce greater
      improvements in employment v. medication, particularly over the longer term.

PMID- 24925987
TI  - Economic suicides in the Great Recession in Europe and North America.
AB  - There has been a substantial rise in 'economic suicides' in the Great Recessions
      afflicting Europe and North America. We estimate that the Great Recession is
      associated with at least 10 000 additional economic suicides between 2008 and
      2010. A critical question for policy and psychiatric practice is whether these
      suicide rises are inevitable. Marked cross-national variations in suicides in the
      recession offer one clue that they are potentially avoidable. Job loss, debt and
      foreclosure increase risks of suicidal thinking. A range of interventions, from
      upstream return-to-work programmes through to antidepressant prescriptions may
      help mitigate suicide risk during economic downturn. 

PMID- 24925988
TI  - Time to speak up for research.

PMID- 24925986
TI  - Effect of polygenic risk scores on depression in childhood trauma.
AB  - BACKGROUND: Research on gene * environment interaction in major depressive
      disorder (MDD) has thus far primarily focused on candidate genes, although
      genetic effects are known to be polygenic. AIMS: To test whether the effect of
      polygenic risk scores on MDD is moderated by childhood trauma. METHOD: The study
      sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340
      screened controls from The Netherlands. Chronic or remitted episodes (severe MDD)
      were present in 956 participants. The occurrence of childhood trauma was assessed
      with the Childhood Trauma Interview and the polygenic risk scores were based on
      genome-wide meta-analysis results from the Psychiatric Genomics Consortium.
      RESULTS: The polygenic risk scores and childhood trauma independently affected
      MDD risk, and evidence was found for interaction as departure from both
      multiplicativity and additivity, indicating that the effect of polygenic risk
      scores on depression is increased in the presence of childhood trauma. The
      interaction effects were similar in predicting all MDD risk and severe MDD risk,
      and explained a proportion of variation in MDD risk comparable to the polygenic
      risk scores themselves. CONCLUSIONS: The interaction effect found between
      polygenic risk scores and childhood trauma implies that (1) studies on direct
      genetic effect on MDD gain power by focusing on individuals exposed to childhood
      trauma, and that (2) individuals with both high polygenic risk scores and
      exposure to childhood trauma are particularly at risk for developing MDD.

PMID- 24925993
TI  - Remote sensing. Carbon-mapping satellite will monitor plants' faint glow.

PMID- 24925994
TI  - Infectious diseases. Polio eradicators struggle to prevent the next outbreak.

PMID- 24925995
TI  - Genetics. Racing for disaster?

PMID- 24925996
TI  - Cell biology. STAP cells succumb to pressure.

PMID- 24925997
TI  - Paleontology. Dinosaur metabolism neither hot nor cold, but just right.

PMID- 24925998
TI  - South America. Legal highs make Uruguay a beacon for marijuana research.

PMID- 24925999
TI  - Mission to MERS.

PMID- 24926000
TI  - A touch of the random.

PMID- 24926001
TI  - Quantum mechanics. The quantum nondemolition derby.

PMID- 24926002
TI  - Molecular biology. Molecular basis of transcription pausing.

PMID- 24926003
TI  - Oceans. A salty start to modern ocean circulation.

PMID- 24926004
TI  - Epidemiology. It helps to be well connected.

PMID- 24926005
TI  - Public health. Measuring the path toward malaria elimination.

PMID- 24926006
TI  - Retrospective. Gary Becker (1930-2014).

PMID- 24926007
TI  - Making waves about spreading weeds.

PMID- 24926008
TI  - Making waves about spreading weeds--response.

PMID- 24926010
TI  - Virology. Comment on "Specific and nonhepatotoxic degradation of nuclear
      hepatitis B virus cccDNA".
AB  - Lucifora et al. (Research Articles, 14 March 2014, p. 1221) report that the
      hepatitis B virus (HBV) transcriptional template, a long-lived covalently closed
      circular DNA (cccDNA) molecule, is degraded noncytolytically by agents that up
      regulate APOBEC3A and 3B. If these results can be independently confirmed, they
      would represent a critical first step toward development of a cure for the 400
      million patients who are chronically infected by HBV. 

PMID- 24926011
TI  - Virology. Response to Comment on "Specific and nonhepatotoxic degradation of
      nuclear hepatitis B virus cccDNA".
AB  - Chisari et al. challenge our central conclusion that the hepatitis B virus (HBV)
      persistent form, the covalently closed circular DNA (cccDNA), is degraded in a
      noncytotoxic and specific fashion in the nucleus of infected hepatocytes.
      Specificity of the assays used, exclusion of cell division or death, and activity
      of APOBEC3 deaminases in the nucleus, however, were addressed in the paper. 

PMID- 24926012
TI  - Paleoceanography. Onset of Mediterranean outflow into the North Atlantic.
AB  - Sediments cored along the southwestern Iberian margin during Integrated Ocean
      Drilling Program Expedition 339 provide constraints on Mediterranean Outflow
      Water (MOW) circulation patterns from the Pliocene epoch to the present day.
      After the Strait of Gibraltar opened (5.33 million years ago), a limited volume
      of MOW entered the Atlantic. Depositional hiatuses indicate erosion by bottom
      currents related to higher volumes of MOW circulating into the North Atlantic,
      beginning in the late Pliocene. The hiatuses coincide with regional tectonic
      events and changes in global thermohaline circulation (THC). This suggests that
      MOW influenced Atlantic Meridional Overturning Circulation (AMOC), THC, and
      climatic shifts by contributing a component of warm, saline water to northern
      latitudes while in turn being influenced by plate tectonics. 

PMID- 24926014
TI  - Quantum nonlocality. Detecting nonlocality in many-body quantum states.
AB  - Intensive studies of entanglement properties have proven essential for our
      understanding of quantum many-body systems. In contrast, much less is known about
      the role of quantum nonlocality in these systems because the available
      multipartite Bell inequalities involve correlations among many particles, which
      are difficult to access experimentally. We constructed multipartite Bell
      inequalities that involve only two-body correlations and show how they reveal the
      nonlocality in many-body systems relevant for nuclear and atomic physics. Our
      inequalities are violated by any number of parties and can be tested by measuring
      total spin components, opening the way to the experimental detection of many-body
      nonlocality, for instance with atomic ensembles. 

PMID- 24926013
TI  - Neuronal repair. Asynchronous therapy restores motor control by rewiring of the
      rat corticospinal tract after stroke.
AB  - The brain exhibits limited capacity for spontaneous restoration of lost motor
      functions after stroke. Rehabilitation is the prevailing clinical approach to
      augment functional recovery, but the scientific basis is poorly understood. Here,
      we show nearly full recovery of skilled forelimb functions in rats with large
      strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory
      protein was applied to boost the sprouting of new fibers, before stabilizing the
      newly formed circuits by intensive training. In contrast, early high-intensity
      training during the growth phase destroyed the effect and led to aberrant fiber
      patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers
      originating in the intact half of the forebrain, side-switching in the spinal
      cord to newly innervate the impaired limb and restore skilled motor function. 

PMID- 24926015
TI  - Quantum gases. Observation of many-body dynamics in long-range tunneling after a
      quantum quench.
AB  - Quantum tunneling is at the heart of many low-temperature phenomena. In strongly
      correlated lattice systems, tunneling is responsible for inducing effective
      interactions, and long-range tunneling substantially alters many-body properties
      in and out of equilibrium. We observe resonantly enhanced long-range quantum
      tunneling in one-dimensional Mott-insulating Hubbard chains that are suddenly
      quenched into a tilted configuration. Higher-order tunneling processes over up to
      five lattice sites are observed as resonances in the number of doubly occupied
      sites when the tilt per site is tuned to integer fractions of the Mott gap. This
      forms a basis for a controlled study of many-body dynamics driven by higher-order
      tunneling and demonstrates that when some degrees of freedom are frozen out,
      phenomena that are driven by small-amplitude tunneling terms can still be
      observed. 

PMID- 24926016
TI  - Earth's interior. Dehydration melting at the top of the lower mantle.
AB  - The high water storage capacity of minerals in Earth's mantle transition zone
      (410- to 660-kilometer depth) implies the possibility of a deep H2O reservoir,
      which could cause dehydration melting of vertically flowing mantle. We examined
      the effects of downwelling from the transition zone into the lower mantle with
      high-pressure laboratory experiments, numerical modeling, and seismic P-to-S
      conversions recorded by a dense seismic array in North America. In experiments,
      the transition of hydrous ringwoodite to perovskite and (Mg,Fe)O produces
      intergranular melt. Detections of abrupt decreases in seismic velocity where
      downwelling mantle is inferred are consistent with partial melt below 660
      kilometers. These results suggest hydration of a large region of the transition
      zone and that dehydration melting may act to trap H2O in the transition zone. 

PMID- 24926017
TI  - Dinosaur physiology. Evidence for mesothermy in dinosaurs.
AB  - Were dinosaurs ectotherms or fast-metabolizing endotherms whose activities were
      unconstrained by temperature? To date, some of the strongest evidence for
      endothermy comes from the rapid growth rates derived from the analysis of fossil
      bones. However, these studies are constrained by a lack of comparative data and
      an appropriate energetic framework. Here we compile data on ontogenetic growth
      for extant and fossil vertebrates, including all major dinosaur clades. Using a
      metabolic scaling approach, we find that growth and metabolic rates follow
      theoretical predictions across clades, although some groups deviate. Moreover,
      when the effects of size and temperature are considered, dinosaur metabolic rates
      were intermediate to those of endotherms and ectotherms and closest to those of
      extant mesotherms. Our results suggest that the modern dichotomy of endothermic
      versus ectothermic is overly simplistic. 

PMID- 24926018
TI  - Nonhuman genetics. Strong male bias drives germline mutation in chimpanzees.
AB  - Germline mutation determines rates of molecular evolution, genetic diversity, and
      fitness load. In humans, the average point mutation rate is 1.2 * 10(-8) per base
      pair per generation, with every additional year of father's age contributing two
      mutations across the genome and males contributing three to four times as many
      mutations as females. To assess whether such patterns are shared with our closest
      living relatives, we sequenced the genomes of a nine-member pedigree of Western
      chimpanzees, Pan troglodytes verus. Our results indicate a mutation rate of 1.2 *
      10(-8) per base pair per generation, but a male contribution seven to eight times
      that of females and a paternal age effect of three mutations per year of father's
      age. Thus, mutation rates and patterns differ between closely related species. 

PMID- 24926020
TI  - Interactions between RNA polymerase and the "core recognition element" counteract
      pausing.
AB  - Transcription elongation is interrupted by sequences that inhibit nucleotide
      addition and cause RNA polymerase (RNAP) to pause. Here, by use of native
      elongating transcript sequencing (NET-seq) and a variant of NET-seq that enables
      analysis of mutant RNAP derivatives in merodiploid cells (mNET-seq), we analyze
      transcriptional pausing genome-wide in vivo in Escherichia coli. We identify a
      consensus pause-inducing sequence element, G-10Y-1G(+1) (where -1 corresponds to
      the position of the RNA 3' end). We demonstrate that sequence-specific
      interactions between RNAP core enzyme and a core recognition element (CRE) that
      stabilize transcription initiation complexes also occur in transcription
      elongation complexes and facilitate pause read-through by stabilizing RNAP in a
      posttranslocated register. Our findings identify key sequence determinants of
      transcriptional pausing and establish that RNAP-CRE interactions modulate
      pausing.

PMID- 24926021
TI  - Disease ecology. Ecological and evolutionary effects of fragmentation on
      infectious disease dynamics.
AB  - Ecological theory predicts that disease incidence increases with increasing
      density of host networks, yet evolutionary theory suggests that host resistance
      increases accordingly. To test the combined effects of ecological and
      evolutionary forces on host-pathogen systems, we analyzed the spatiotemporal
      dynamics of a plant (Plantago lanceolata)-fungal pathogen (Podosphaera
      plantaginis)relationship for 12 years in over 4000 host populations. Disease
      prevalence at the metapopulation level was low, with high annual pathogen
      extinction rates balanced by frequent (re-)colonizations. Highly connected host
      populations experienced less pathogen colonization and higher pathogen extinction
      rates than expected; a laboratory assay confirmed that this phenomenon was caused
      by higher levels of disease resistance in highly connected host populations. 

PMID- 24926019
TI  - Human genetics. The genetics of Mexico recapitulates Native American substructure
      and affects biomedical traits.
AB  - Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of
      human genome-wide variation from this region remain largely uncharacterized. We
      studied genomic variation within Mexico from over 1000 individuals representing
      20 indigenous and 11 mestizo populations. We found striking genetic
      stratification among indigenous populations within Mexico at varying degrees of
      geographic isolation. Some groups were as differentiated as Europeans are from
      East Asians. Pre-Columbian genetic substructure is recapitulated in the
      indigenous ancestry of admixed mestizo individuals across the country.
      Furthermore, two independently phenotyped cohorts of Mexicans and Mexican
      Americans showed a significant association between subcontinental ancestry and
      lung function. Thus, accounting for fine-scale ancestry patterns is critical for
      medical and population genetic studies within Mexico, in Mexican-descent
      populations, and likely in many other populations worldwide. 

PMID- 24926022
TI  - Comparative behavior. Anxiety-like behavior in crayfish is controlled by
      serotonin.
AB  - Anxiety, a behavioral consequence of stress, has been characterized in humans and
      some vertebrates, but not invertebrates. Here, we demonstrate that after exposure
      to stress, crayfish sustainably avoided the aversive illuminated arms of an
      aquatic plus-maze. This behavior was correlated with an increase in brain
      serotonin and was abolished by the injection of the benzodiazepine anxiolytic
      chlordiazepoxide. Serotonin injection into unstressed crayfish induced avoidance;
      again, this effect was reversed by injection with chlordiazepoxide. Our results
      demonstrate that crayfish exhibit a form of anxiety similar to that described in
      vertebrates, suggesting the conservation of several underlying mechanisms during
      evolution. Analyses of this ancestral behavior in a simple model reveal a new
      route to understanding anxiety and may alter our conceptions of the emotional
      status of invertebrates. 

PMID- 24926023
TI  - The fun of science.

PMID- 24926025
TI  - Controlling the HIV epidemic with antiretrovirals: moving from consensus to
      implementation.
AB  - The second Controlling the HIV With Antiretrovirals evidence summit was held 22
      24 September 2013, in London, England. This preface summarizes the summit's
      background and key themes, and is an introduction to a series of articles written
      by select summit faculty and featured in this supplement. In many respects, the
      supplement can serve as a roadmap for how to move from general consensus around
      to wider scale implementation of a comprehensive menu of interventions to control
      the HIV epidemic.

PMID- 24926024
TI  - Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration.
AB  - Tissues rely upon stem cells for homeostasis and repair. Recent studies show that
      the fate and multilineage potential of epithelial stem cells can change depending
      on whether a stem cell exists within its resident niche and responds to normal
      tissue homeostasis, whether it is mobilized to repair a wound, or whether it is
      taken from its niche and challenged to de novo tissue morphogenesis after
      transplantation. In this Review, we discuss how different populations of
      naturally lineage-restricted stem cells and committed progenitors can display
      remarkable plasticity and reversibility and reacquire long-term self-renewing
      capacities and multilineage differentiation potential during physiological and
      regenerative conditions. We also discuss the implications of cellular plasticity
      for regenerative medicine and for cancer. 

PMID- 24926026
TI  - A paradigm shift: focus on the HIV prevention continuum.
AB  - The human immunodeficiency virus (HIV) prevention continuum is a framework that
      illustrates the interconnectedness of each step in the spectrum of prevention
      services, while emphasizing that all steps are needed to decrease HIV acquisition
      and transmission. This continuum, similar to the HIV care continuum, begins with
      HIV testing followed by linkage of HIV-uninfected persons to prevention services,
      retention in such services, and adherence to prevention interventions with
      repeated HIV testing to monitor for HIV acquisition. To advance the global goal
      of zero new HIV infections, individuals must receive the entire continuum of
      prevention services, and no partial credit can be given to achievement of one
      step in isolation of all steps in the continuum.

PMID- 24926027
TI  - Modeling scenarios for the end of AIDS.
AB  - At the end of 2012, 3 decades after the human immunodeficiency virus (HIV) was
      first identified, neither a cure nor a fully preventive vaccine was available.
      Despite multiple efforts, the epidemic remains an exceptional public health
      challenge. At the end of 2012, it was estimated that, globally, 35 million people
      were living with HIV, 2.3 million had become newly infected, and 1.6 million had
      died from AIDS-related causes. Despite substantial prevention efforts and
      increases in the number of individuals on highly active antiretroviral therapy
      (HAART), the epidemic burden continues to be high. Here, we provide a brief
      overview of the epidemiology of HIV transmission, the work that has been done to
      date regarding HIV modeling in different settings around the world, and how to
      finance the response to the HIV epidemic. In addition, we suggest discussion
      topics on how to move forward with the prevention agenda and highlight the role
      of treatment as prevention (TasP) in curbing the epidemic.

PMID- 24926029
TI  - Who pays and why? Costs, effectiveness, and feasibility of HIV treatment as
      prevention.
AB  - Treatment as prevention (TasP) has been added to the toolbox of human
      immunodeficiency virus (HIV) prevention technologies, and countries are at
      different stages of TasP deployment. In this article we review some of the cost
      implications and summarize effectiveness data from different settings. Also, we
      reflect on the affordability and feasibility of programmatic deployment as well
      as the multiple challenges of maintaining service quality while HIV treatment
      programs grow in size and complexity. We conclude that in low-resource settings,
      TasP progress will be very incremental with progressively earlier treatment
      initiation while working within the capacity and resource constraints of the
      respective healthcare systems. In the long-term, feasibility will rely on
      complementary interventions to reduce new HIV infections, such as male
      circumcision, and on demand creation for early treatment uptake as well as
      adherence. TasP holds potential for moving us closer to the global goal of ending
      AIDS.

PMID- 24926028
TI  - Addressing the Achilles' heel in the HIV care continuum for the success of a test
      and-treat strategy to achieve an AIDS-free generation.
AB  - Mathematical models and recent data from ecological, observational, and
      experimental studies show that antiretroviral therapy (ART) is effective for both
      treatment and prevention of HIV, validating the treatment as prevention (TasP)
      approach. Data from a variety of settings, including resource-rich and -limited
      sites, show that patient attrition occurs at each stage of the human
      immunodeficiency virus (HIV) treatment cascade, starting with the percent unaware
      of their HIV infection in a population and linkage to care after diagnosis,
      assessment of ART readiness, receipt of ART, and finally long-term virologic
      suppression. Therefore, in order to implement TasP, we must first define
      practical and effective linkage to care, acceptability of treatment, and
      adherence and retention monitoring strategies, as well as the cost-effectiveness
      of such strategies. Ending this pandemic will require the combination of
      political will, resources, and novel effective interventions that are not only
      feasible and cost effective but also likely to be used in combination across
      successive steps on the HIV treatment cascade.

PMID- 24926030
TI  - Leveraging HIV treatment to end AIDS, stop new HIV infections, and avoid the cost
      of inaction.
AB  - We have the tools at our disposal to significantly bend AIDS-related morbidity
      and mortality curves and reduce human immunodeficiency virus (HIV) incidence. It
      is thus essential to redouble our efforts to reach the goal of placing 15 million
      people on life-saving and -enhancing antiretroviral therapy (ART) by 2015. In
      reaching this milestone, we can write a new chapter in the history of global
      health, demonstrating that a robust, multidimensional response can succeed
      against a complex pandemic that presents as many social and political challenges
      as it does medical ones. This milestone is also critical to advance our ultimate
      goal of ending AIDS by maximizing the therapeutic and preventive effects of ART,
      which translates into a world in which AIDS-related deaths and new HIV infections
      are exceedingly rare.

PMID- 24926031
TI  - Bioethical challenges with HIV treatment as prevention.
AB  - To best realize the opportunities afforded by treatment as prevention, important
      ethical challenges must be addressed, including those related to acceptability,
      safety, and effectiveness, as well as alternatives. Absent universal access to
      quality antiretroviral treatment, safety, fairness, and allocation must also be
      considered.

PMID- 24926032
TI  - Treatment as prevention: arriving at community consensus.
AB  - At a satellite meeting preceding the 2013 Controlling the HIV Epidemic With
      Antiretrovirals evidence summit in London, England, a group of organizations and
      advocates discussed and formulated the final draft of a document, the Community
      Consensus Statement on the Use of Antiretroviral Therapy in Preventing HIV
      Transmission, that succinctly outlines a set of principles that should be
      followed in the provision of antiretroviral therapy to people with living with
      human immunodeficiency virus (HIV) for the purposes of preventing HIV,
      particularly as a public health measure. The satellite meeting's conclusions were
      subsequently outlined in a presentation and panel discussion at the evidence
      summit. 

PMID- 24926034
TI  - Antiretroviral chemoprophylaxis: state of evidence and the research agenda.
AB  - Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease
      human immunodeficiency virus (HIV) incidence in studies of men who have sex with
      men, heterosexual men and women, and injecting drug users. One study of
      pericoital tenofovir gel demonstrated that it reduced HIV incidence in South
      African women. However, other studies of African women failed to demonstrate
      protection with either oral tenofovir or tenofovir-emtricitabine, or daily
      tenofovir gel. The magnitude of PrEP protection appears to be highly correlated
      with medication adherence. New studies are evaluating whether different
      antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase
      inhibitors. Different formulations are also being evaluated, including gels,
      films, vaginal rings, and injectable medication. Although PrEP efficacy has been
      demonstrated, and several normative bodies (eg, the US Food and Drug
      Administration) have approved PrEP for clinical use, uptake has been slow.
      Reasons may include lack of sufficient provider and consumer education, residual
      concerns about costs, potential long-term toxicities, and behavioral
      disinhibition. Additional work is under way to determine how to best educate
      consumers and providers about optimal adherence and to use PrEP in conjunction
      with risk mitigation.

PMID- 24926033
TI  - Biomedical prevention: state of the science.
AB  - Preexposure prophylaxis (PrEP) and treatment as prevention (TasP) involve the use
      of antiretroviral (ARV) drugs by human immunodeficiency virus (HIV)-negative and 
      positive individuals to reduce HIV acquisition and transmission, respectively.
      Clinical science has delivered a consistently high effect size for TasP and a
      range from 0%-73% reduction in incidence across placebo-controlled PrEP trials.
      However, the quality of evidence for PrEP compares favorably with evidence for
      postexposure prophylaxis (PEP). It is clear from treatment programs and PrEP
      trials that daily adherence presents challenges to a large proportion of the
      population. Although there are factors associated with inconsistent use (ie,
      younger age), they do not assist clinicians at the point of care. There are
      additional provider concerns about PrEP (covering cost of drug and delivery,
      undermining condom promotion, and facilitating resistant strains) that have
      delayed widespread acceptance. These issues need to be addressed in order to
      realize the full public health potential of antiretrovirals.

PMID- 24926035
TI  - Pharmacology lessons from chemoprophylaxis studies.
AB  - Pharmacological studies in the context of preexposure prophylaxis (PrEP) for
      human immunodeficiency virus (HIV) are fundamental to inform on different drug
      pharmacokinetics, pharmacodynamics, and pharmacogenetics in view of the absence
      of easily measurable surrogate markers of efficacy. Although the combination of
      tenofovir and emtricitabine is the only PrEP agent that was studied and showed
      efficacy in preventing HIV transmission, prospective randomized clinical trials
      have reported varying efficacy due to poor adherence to the drug. Importantly,
      this could be overcome by the introduction of long-acting injectable PrEP agents,
      which may be administered monthly and ensure optimal and prolonged drug exposure
      in HIV target tissues. Notably, clinical pharmacology studies play a central role
      in interpreting drug concentration-responses and optimal drug exposure
      achievement.

PMID- 24926036
TI  - Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of
      evidence.
AB  - Despite considerable discussion and debate about adherence to preexposure
      prophylaxis (PrEP) for human immunodeficiency virus (HIV), scant data are
      available that characterize patterns of adherence to open-label PrEP. The current
      evidence base is instead dominated by research on adherence to placebo-controlled
      investigational drug by way of drug detection in active-arm participants of large
      randomized controlled trials (RCTs). Important differences between the context of
      blinded RCTs and open-label use suggest caution when generalizing from study
      product adherence to real-world PrEP use. Evidence specific to open-label PrEP
      adherence is presently sparse but will expand rapidly over the next few years as
      roll-out, demonstration projects, and more rigorous research collect and present
      findings. The current evidence bases established cannot yet predict uptake,
      adherence, or persistence with open-label effective PrEP. Emerging evidence
      suggests that some cohorts could execute better adherence in open-label use vs
      placebo-controlled research. Uptake of PrEP is presently slow in the United
      States; whether this changes as grassroots and community efforts increase
      awareness of PrEP as an effective HIV prevention option remains to be determined.
      As recommended by multiple guidelines for PrEP use, all current demonstration
      projects offer PrEP education and/or counseling. PrEP support approaches
      generally fall into community-based, technology, monitoring, and integrated
      sexual health promotion approaches. Developing and implementing research that
      moves beyond simple correlates of either study product use or open-label PrEP
      adherence toward more comprehensive models of sociobehavioral and socioecological
      adherence determinants would greatly accelerate progress. Intervention research
      is needed to identify effective models of support for open-label PrEP adherence.

PMID- 24926037
TI  - Global response to HIV: treatment as prevention, or treatment for treatment?
AB  - The concept of "treatment as prevention" has emerged as a means to curb the
      global HIV epidemic. There is, however, still ongoing debate about the evidence
      on when to start antiretroviral therapy in resource-poor settings. Critics have
      brought forward multiple arguments against a "test and treat" approach, including
      the potential burden of such a strategy on weak health systems and a presumed
      lack of scientific support for individual patient benefit of early treatment
      initiation. In this article, we highlight the societal and individual advantages
      of treatment as prevention in resource-poor settings. We argue that the available
      evidence renders the discussion on when to start antiretroviral therapy
      unnecessary and that, instead, efforts should be aimed at offering treatment as
      soon as possible.

PMID- 24926038
TI  - A versatile model of open-fracture infection : a contaminated segmental rat femur
      defect.
AB  - OBJECTIVES: The purpose of this study was to refine an accepted contaminated rat
      femur defect model to result in an infection rate of approximately 50%. This
      threshold will allow examination of treatments aimed at reducing infection in
      open fractures with less risk of type II error. METHODS: Defects were created in
      the stablised femurs of anaethetised rats, contaminated with Staphylococcus
      aureus and then debrided and irrigated six hours later. After 14 days, the bone
      and implants were harvested for separate microbiological analysis. This basic
      model was developed in several studies by varying the quantity of bacterial
      inoculation, introducing various doses of systemic antibiotics with and without
      local antibiotics. RESULTS: The bacterial inoculation associated with a 50%
      infection rate was established as 1 * 10(2) colony forming units (CFU). With an
      initial bacterial inoculum of 1 * 10(5) CFU, the dose of systemic antibiotics
      associated with 50% infection was 5 mg/Kg of cafazolin injected sub-cutaneously
      every 12 hours, starting at the time of the first debridment and continuing for
      72 hours (seven doses). The systemic dose of cafazolin was lowered to 2 mg/Kg
      when antibiotic polymethyl methacrylate beads were used concurrently with the
      same amount of bacterial inoculation. CONCLUSION: This model of open fracture
      infection has been further refined with potential for local and systemic
      antibiotics. This is a versatile model and with the concepts presented herein, it
      can be modified to evaluate various emerging therapies and concepts for open
      fractures. Cite this article: Bone Joint Res 2014;3:187-92.

PMID- 24926039
TI  - Processed and unprocessed red meat consumption and risk of heart failure:
      prospective study of men.
AB  - BACKGROUND: Epidemiological studies of red meat consumption in relation to risk
      of heart failure (HF) are scarce. We examined the associations of unprocessed and
      processed red meat consumption with HF incidence and mortality in men. METHODS
      AND RESULTS: The population-based prospective Cohort of Swedish Men included 37
      035 men, aged 45 to 79 years, with no history of HF, ischemic heart disease, or
      cancer at baseline. Meat consumption was assessed with a self-administered
      questionnaire in 1997. During a mean follow-up of 11.8 years, 2891 incidences and
      266 deaths from HF were ascertained. Consumption of processed meat was
      statistically significant positively associated with risk of HF in both age- and
      multivariable-adjusted models. Men who consumed >=75 g/d processed meat compared
      with those who consumed <25 g/d had a 1.28 (95% confidence interval, 1.10-1.48, P
      trend=0.01) higher risk of HF incidence and 2.43 (95% confidence interval, 1.52
      3.88, P trend<0.001) higher risk of HF mortality. The consumption of unprocessed
      meat was not associated with increased risk of incidence of HF or mortality from
      HF. CONCLUSIONS: Findings from this prospective study of men with low to moderate
      red meat consumption indicate that processed red meat consumption, but not
      unprocessed red meat, is associated with an increased risk of HF.

PMID- 24926040
TI  - A peer-led, community-based rapid HIV testing intervention among untested men who
      have sex with men in China: an operational model for expansion of HIV testing and
      linkage to care.
AB  - OBJECTIVES: To examine outcomes of a peer-led, community-based intervention
      providing rapid HIV testing and case management for linkage to care for untested
      men who have sex with men (MSM) in China. METHODS: Rapid HIV testing was
      performed by trained peer volunteers of a community-based organisation (CBO) in
      three cities of Jiangsu province at MSM-oriented venues. MSM screened positive
      were referred and accompanied to local government health agencies (Centres for
      Disease Control and Prevention (CDC)) for confirmatory HIV testing and provided
      social support for up to 1 month. Data for the programme were compared with
      sentinel surveillance surveys of MSM conducted by the national and provincial CDC
      in the province during the same year to assess differences in the populations
      reached, in HIV positivity, and linkage to HIV care. RESULTS: A total of 512
      previously untested MSM were tested by the CBO programme in 6 months. Compared
      with those in the surveillance surveys, MSM tested by the CBO were significantly
      more likely to be younger, single, non-resident of the province, more educated
      and used condoms less frequently. Higher proportions of HIV-positive MSM screened
      by the CBO received their confirmatory test results (98.1% vs 72.6%, p<0.001) and
      linked to care (90.4% vs 42.0%, p<0.001). CONCLUSIONS: Trained peers providing
      rapid HIV testing with social support and case management through the early
      period following diagnosis can efficiently expand HIV testing and improve linkage
      to care among MSM in China.

PMID- 24926041
TI  - Sex on demand: geosocial networking phone apps and risk of sexually transmitted
      infections among a cross-sectional sample of men who have sex with men in Los
      Angeles County.
AB  - BACKGROUND: Geosocial networking applications (GSN apps) used for meeting sexual
      partners have become increasingly popular with men who have sex with men (MSM)
      since 2009. The current study aimed to determine if self-identified HIV-negative,
      MSM clinic attendees who used GSN apps have an increased incidence of sexually
      transmitted infections (STI) compared to self-identified HIV-negative, MSM
      attendees who met sexual partners via in-person venues, such as bars or clubs or
      through MSM-specific hook-up websites. METHODS: Data were collected between
      August 2011 and January 2013 on all self-identified HIV-negative, MSM clients
      visiting the L.A. Gay & Lesbian Center for STI screening. A total of 7184
      individuals tested for STIs and self-reported behaviours on drug use and social
      networking methods to meet sexual partners. Multivariate logistic regression
      models were used to analyse the results. RESULTS: Individuals who used GSN apps
      for meeting sexual partners had greater odds of testing positive for gonorrhoea
      (OR: 1.25; 95% CI 1.06 to 1.48) and for chlamydia (OR: 1.37; 95% CI 1.13 to 1.65)
      compared to individuals who met partners through in-person methods only. There
      were no significant differences in syphilis and HIV incidence between those who
      met partners via in-person venues only, on the internet or through GSN apps.
      CONCLUSIONS: The present study concludes that sexual health clinic MSM attendees
      who are meeting on GSN apps are at greater risk for gonorrhoea and chlamydia than
      MSM attendees who meet in-person or on the internet. Future interventions should
      explore the use of these novel technologies for testing promotion, prevention and
      education.

PMID- 24926042
TI  - Complete Genome Sequence of Bacillus cereus Sensu Lato Bacteriophage Bcp1.
AB  - Bacillus cereus sensu lato organisms are an ecologically diverse group that
      includes etiologic agents of food poisoning, periodontal disease, and anthrax.
      The recently identified Bcp1 bacteriophage infects B. cereus sensu lato and is
      being developed as a therapeutic decontamination agent and diagnostic
      countermeasure. We announce the complete genome sequence of Bcp1. 

PMID- 24926043
TI  - Identification of a Novel HIV-1 Circulating Recombinant Form (CRF72_BF1) in Deep
      Sequencing Data from Blood Donors in Southeastern Brazil.
AB  - We report the identification of a novel HIV-1 circulating recombinant form
      (CRF72_BF1) in deep sequencing data from peripheral blood mononuclear cells
      (PBMC) of five blood donors in southeastern Brazil. Detection of this circulating
      recombinant form (CRF) confirms the need for effective surveillance to monitor
      the prevalence and distribution of HIV variants in a variety of settings in
      Brazil. 

PMID- 24926044
TI  - Yersinia pseudotuberculosis ST42 (O:1) Strain Misidentified as Yersinia pestis by
      Mass Spectrometry Analysis.
AB  - We report here the draft sequence of strain CEB14_0017, alias HIAD_DUP, recovered
      from a human patient and initially identified as Yersinia pestis by mass
      spectrometry analysis. Genotyping based on tandem repeat polymorphism assigned
      the strain to Yersinia pseudotuberculosis sequence type 42 (ST42). The total
      assembly length is 4,894,739 bp. 

PMID- 24926045
TI  - Draft Genome Sequences of Two Clinical Isolates of Streptococcus mutans.
AB  - We report the draft genome sequences of PKUSS-HG01 and PKUSS-LG01, two clinical
      isolates of Streptococcus mutans from human dental plaque. The genomics
      information will facilitate the study of the mechanisms of pathogenicity and
      evolution of S. mutans. 

PMID- 24926046
TI  - Draft Genome Sequence of Insecticidal Streptomyces sp. Strain PCS3-D2, Isolated
      from Mangrove Soil in Philippines.
AB  - A draft genome sequence of a Streptomyces sp. isolated from mangrove soil in
      Cebu, Philippines, is described here. This isolate produced compounds with
      contact insecticidal activity against important corn pests. The genome contains
      7,479,793 bp (in 27 scaffolds), 6,297 predicted genes, and 29 secondary
      metabolite biosynthetic gene clusters. 

PMID- 24926047
TI  - Genome sequences of porcine epidemic diarrhea virus: in vivo and in vitro
      phenotypes.
AB  - Since the outbreak of porcine epidemic diarrhea virus (PEDV) in May 2013, U.S.
      swine producers have lost almost five million baby pigs. In an attempt to
      understand the evolution of PEDV in the United States and possibly develop a
      control strategy, we compared the genome sequences of a PEDV strain isolated from
      an infected piglet against its in vitro adapted version. The original PEDV strain
      was grown in Vero cells and passed 10 times serially in a MARC145 cell line. The
      sequence analysis of the native PEDV strain and in vitro passaged virus shows
      that the cell culture adaptation specifically modifies PEDV spike protein whereas
      the open reading frame 1a/b (ORF1a/b)-encoded polyprotein, the nucleoprotein,
      NS3B (ORF3), and membrane and envelope proteins remain unchanged. 

PMID- 24926048
TI  - Complete Genome Sequence of Foot-and-Mouth Disease Virus Type A Circulating in
      Bangladesh.
AB  - The complete genome sequence of a foot-and-and mouth disease virus (FMDV) type A
      strain (BAN/GA/Sa-197/2013), isolated from Gazipur in Bangladesh, revealed an 84
      nucleotide insertion within the 5'-untranslated region (UTR), a lengthened
      poly(C) tract, and amino acid substitutions at the VP1 region compared to the
      available genome sequence of the vaccine strain (GenBank accession no. HM854025).

PMID- 24926049
TI  - Genome Sequence of SCB34, a Sequence Type 131 Multidrug-Resistant Escherichia
      coli Isolate Causing Neonatal Early-Onset Sepsis.
AB  - SCB34 is a sequence type 131, highly invasive, multidrug-resistant Escherichia
      coli isolate that produced neonatal bacteremia. Whole-genome sequencing was
      performed using a 250-bp library on the Illumina MiSeq platform; 5,910,264 reads
      were assembled de novo using the A5 assembly pipeline. The total contig length
      was 5,227,742 bp; the RAST server was used for annotation. 

PMID- 24926050
TI  - Genome Sequence of the epsilon-Poly-l-Lysine-Producing Strain Streptomyces
      albulus NK660, Isolated from Soil in Gutian, Fujian Province, China.
AB  - We determined the complete genome sequence of a soil bacterium, Streptomyces
      albulus NK660. It can produce epsilon-poly-l-lysine, which has antimicrobial
      activity against a spectrum of microorganisms. The genome of S. albulus NK660
      contains a 9,360,281-bp linear chromosome and a 12,120-bp linear plasmid. 

PMID- 24926051
TI  - Draft Genome Sequence of Photobacterium halotolerans S2753, Producer of Bioactive
      Secondary Metabolites.
AB  - We report here the whole draft genome sequence of marine isolate Photobacterium
      halotolerans S2753, which produces the known antibiotic holomycin and also
      ngercheumicins and solonamides A and B, which interfere with virulence of
      methicillin-resistant Staphylococcus aureus strains by interacting with the
      quorum-sensing system. 

PMID- 24926052
TI  - Draft Genome Sequence of a Rare Smut Relative, Tilletiaria anomala UBC 951.
AB  - The draft genome sequence of the smut fungus Tilletiaria anomala UBC 951
      (Basidiomycota, Ustilaginomycotina) is presented. The sequenced genome size is
      18.7 Mb, consisting of 289 scaffolds and a total of 6,810 predicted genes. This
      is the first genome sequence published for a fungus in the order
      Georgefisheriales (Exobasidiomycetes). 

PMID- 24926053
TI  - Draft Genome Sequence of Colletotrichum sublineola, a Destructive Pathogen of
      Cultivated Sorghum.
AB  - Colletotrichum sublineola is a filamentous fungus that causes anthracnose disease
      on sorghum. We report a draft whole-genome shotgun sequence and gene annotation
      of the nuclear genome of this fungus using Illumina sequencing. 

PMID- 24926054
TI  - Draft Genome Sequences of Two Genetic Variant Strains of Edwardsiella piscicida,
      JF1305 and RSB1309, Isolated from Olive Flounder (Paralichythys olivaceus) and
      Red Sea Bream (Pagrus major) Cultured in Japan, Respectively.
AB  - Edwardsiella piscicida is a new species discovered within the group of organisms
      traditionally classified as Edwardsiella tarda. We present draft genome sequences
      of two variant strains of E. piscicida, JF1305 and RSB1309. Differences in
      protein-coding sequence between these isolates are associated with virulence,
      disease, and defense, suggesting differences in pathogenicity. 

PMID- 24926055
TI  - Genome Sequence of Thermoanaerobaculum aquaticum MP-01T, the First Cultivated
      Member of Acidobacteria Subdivision 23, Isolated from a Hot Spring.
AB  - Thermoanaerobaculum aquaticum MP-01(T) is currently the only cultivated and
      described member of Acidobacteria subdivision 23. Here, we report the genome
      sequence for this novel microorganism that was isolated from a hot spring. 

PMID- 24926056
TI  - Draft Genome Sequence of Aeromonas hydrophila Strain Ae34, Isolated from a
      Septicemic and Moribund Koi Carp (Cyprinus carpio koi), a Freshwater Aquarium
      Fish.
AB  - Aeromonas hydrophila is an important opportunistic pathogen that infects a
      variety of aquatic and terrestrial animals, including humans. We report here the
      draft genome sequence of A. hydrophila Ae34, a multidrug-resistant isolate from
      the kidney of a moribund koi carp (Ciprinus carpio koi) with signs of hemorrhagic
      septicemia. 

PMID- 24926057
TI  - Complete Genome Sequence of Amino Acid-Utilizing Eubacterium acidaminophilum al-2
      (DSM 3953).
AB  - Eubacterium acidaminophilum is a strictly anaerobic, Gram-positive, rod-shaped
      bacterium which belongs to cluster XI of the Clostridia. It ferments amino acids
      by a Stickland reaction. The genome harbors a chromosome (2.25 Mb) and a
      megaplasmid (0.8 Mb). It contains several gene clusters coding for selenocysteine
      containing, glycine-derived, and amino acid-degrading reductases. 

PMID- 24926058
TI  - Complete genome sequence of pronghorn virus, a pestivirus.
AB  - The complete genome sequence of pronghorn virus, a member of the Pestivirus genus
      of the family Flaviviridae, was determined here. The virus, originally isolated
      from a pronghorn antelope, has a genome of 12,273 nucleotides, with a single open
      reading frame of 11,694 bases encoding 3,897 amino acids. 

PMID- 24926059
TI  - Draft Genome Sequence of Stenotrophomonas maltophilia Strain M30, Isolated from a
      Chronic Pressure Ulcer in an Elderly Patient.
AB  - Stenotrophomonas maltophilia is an emerging opportunistic pathogen with an
      increasing prevalence of multidrug-resistant strains. Here, we report the draft
      genome sequence of S. maltophilia strain M30, isolated from a pressure ulcer in
      an elderly patient. 

PMID- 24926060
TI  - Genome Sequence of Aeromonas taiwanensis LMG 24683T, a Clinical Wound Isolate
      from Taiwan.
AB  - Aeromonas taiwanensis was first described in 2010 on the basis of one clinical
      wound isolate (strain LMG 24683(T) = A2-50(T) = CECT 7403(T)) from Taiwan. We
      present here the genome sequence of A. taiwanensis LMG 24683(T), which carries
      several genes encoding virulence determinants and Ambler class C and D beta
      lactamases. 

PMID- 24926061
TI  - Draft Genome Sequences of Nine Enteropathogenic Escherichia coli Strains from
      Kenya.
AB  - We report here the draft genome sequences of nine enteropathogenic Escherichia
      coli (EPEC) strains isolated from children in Kenya who died during
      hospitalization with diarrhea. Each of the isolates possess the EPEC adherence
      factor (EAF) plasmid encoding the bundle-forming pilus, which is characteristic
      of EPEC. These isolates represent diverse serogroups and EPEC phylogenomic
      lineages. 

PMID- 24926062
TI  - Genome Sequences of Strain ATCC 29281 and Pin and Northern Red Oak Isolates of
      Lonsdalea quercina subsp. quercina.
AB  - Two bacteria identified as Lonsdalea quercina subsp. quercina were isolated from
      oak trees showing symptoms of drippy blight. Here, we present their draft genome
      assemblies, as well as that of the type strain of this species. To our knowledge,
      these are the first published genome sequences of this subspecies of Lonsdalea
      quercina. 

PMID- 24926063
TI  - Genetic Characterization of HIV-1 Subtype D Near-Full-Length Proviral Genomes by
      Illumina Massively Parallel Sequencing Technology.
AB  - This study describes the near-full-length genome deep sequencing of two HIV-1
      subtype D strains identified in blood donors in Rio de Janeiro, Brazil, in what
      seems to have been a small restricted subtype D epidemic in the country. 

PMID- 24926064
TI  - Draft Genome Sequence of Bacillus pumilus 7P, Isolated from the Soil of the
      Tatarstan Republic, Russia.
AB  - Here, we present a draft genome sequence of Bacillus pumilus strain 7P. This
      strain was isolated from soil as an extracellular RNase-producing microorganism.
      The RNase of B. pumilus 7P is considered to be a potential antiviral and
      therapeutic antitumor agent, and it might be appropriate for agriculture and
      academic synthesis of oligoribonucleotides. 

PMID- 24926065
TI  - Paving the road to MRD-guided treatment in CLL.

PMID- 24926066
TI  - An unsung runt 6e isoform for HSC expansion.

PMID- 24926067
TI  - Symptom burden in hematologic malignancies.

PMID- 24926068
TI  - Validation is a dish oft served cold.

PMID- 24926070
TI  - In search of the source of factor VIII.

PMID- 24926071
TI  - JAK inhibitors: a home run for GVHD patients?

PMID- 24926069
TI  - Erythroid DAMPs drive inflammation in SCD.

PMID- 24926075
TI  - Acupuncture for treatment of secondary osteoporosis in patients with spinal cord
      injury: a controlled study.
AB  - OBJECTIVE: We explored the effect of adjunctive acupuncture on secondary
      osteoporosis in patients with spinal cord injury (SCI). METHODS: Patients with
      subacute SCI were recruited and divided into two groups by patient choice: group
      1 patients received standard combination therapy and group 2 patients received
      combination therapy plus acupuncture for 3 months. The concentrations of IgG, IgM
      and tumour necrosis factor alpha (TNFalpha) in serum and the bone mineral density
      were measured before and after treatment. RESULT: The decrease in the
      concentration of TNFalpha and IgM in patients in group 2 compared with those in
      group 1 was statistically significant. The IgG level showed no significant change
      in either group. Bone mineral density increased more after adjunctive
      acupuncture, but the difference was not significant. CONCLUSIONS: Further
      research is needed to determine whether acupuncture as an adjunct to combination
      therapy can reduce osteoporosis in patients with subacute SCI. TRIAL REGISTRATION
      NUMBER: P153-2008-36.

PMID- 24926077
TI  - Team-based learning.

PMID- 24926076
TI  - A critical role for the vascular endothelium in functional neurovascular coupling
      in the brain.
AB  - BACKGROUND: The functional modulation of blood flow in the brain is critical for
      brain health and is the basis of contrast in functional magnetic resonance
      imaging. There is evident coupling between increases in neuronal activity and
      increases in local blood flow; however, many aspects of this neurovascular
      coupling remain unexplained by current models. Based on the rapid dilation of
      distant pial arteries during cortical functional hyperemia, we hypothesized that
      endothelial signaling may play a key role in the long-range propagation of
      vasodilation during functional hyperemia in the brain. Although well
      characterized in the peripheral vasculature, endothelial involvement in
      functional neurovascular coupling has not been demonstrated. METHODS AND RESULTS:
      We combined in vivo exposed-cortex multispectral optical intrinsic signal imaging
      (MS-OISI) with a novel in vivo implementation of the light-dye technique to
      record the cortical hemodynamic response to somatosensory stimulus in rats before
      and after spatially selective endothelial disruption. We demonstrate that
      discrete interruption of endothelial signaling halts propagation of stimulus
      evoked vasodilation in pial arteries, and that wide-field endothelial disruption
      in pial arteries significantly attenuates the hemodynamic response to stimulus,
      particularly the early, rapid increase and peak in hyperemia. CONCLUSIONS:
      Involvement of endothelial pathways in functional neurovascular coupling provides
      new explanations for the spatial and temporal features of the hemodynamic
      response to stimulus and could explain previous results that were interpreted as
      evidence for astrocyte-mediated control of functional hyperemia. Our results
      unify many aspects of blood flow regulation in the brain and body and prompt new
      investigation of direct links between systemic cardiovascular disease and neural
      deficits.

PMID- 24926078
TI  - Do not assume. Information flow and the electronic medical record.

PMID- 24926079
TI  - Pathology consultation on prostate-specific antigen testing.
AB  - OBJECTIVES: To provide clarity on the pros and cons of using prostate-specific
      antigen (PSA) as a screening tool for prostate cancer. METHODS: Case scenarios
      and a literature review of recently published clinical trial data are presented
      to provide evidence of the controversy. RESULTS: PSA is a sensitive biomarker for
      detecting diseases of the prostate, but it is limited in its ability to
      distinguish cancerous from noncancerous conditions or aggressive from indolent
      cancers and has resulted in a considerable amount of overdiagnosis and
      overtreatment. CONCLUSIONS: The analytical methodology for total PSA testing is
      both reliable and cost-effective, but patients should be encouraged to talk to
      their providers to understand the benefits and harms associated with this
      testing.

PMID- 24926080
TI  - The effects of under 6 hours of formalin fixation on hormone receptor and HER2
      expression in invasive breast cancer: a systematic review.
AB  - OBJECTIVES: A systematic review of the literature was performed to identify
      whether minimum formalin fixation time may be reduced for reliable
      immunohistochemical assessment of estrogen receptor (ER), progesterone receptor
      (PR), and human epidermal growth factor receptor 2 (HER2). METHODS: PubMed,
      EMBASE, and the Cochrane Library were systematically searched for studies
      addressing effects of brief tissue fixation (<6 hours) on the analysis of ER, PR,
      or HER2 expression in patients with breast cancer. RESULTS: Five publications
      reported effects of brief fixation on ER, PR, or HER2 expression. Four studies
      showed similar receptor expression of short fixation compared with recommended
      fixation time (6-72 hours). One publication found that a minimum fixation time of
      6 to 8 hours is necessary for reliable ER results. CONCLUSIONS: Available data on
      the effect of brief fixation on receptor status are limited. However, brief
      fixation of very highly expressing breast cancers does not seem to alter ER, PR,
      and HER2 status. Nevertheless, scoring inconsistencies have been observed.
      Further research is required in larger study populations with more low-expressing
      cases for future validation.

PMID- 24926081
TI  - Team-based learning in a pathology residency training program.
AB  - OBJECTIVES: Team-based learning (TBL) has been integrated into undergraduate and
      medical education curricula in many institutions. However, TBL has not been
      widely introduced into postgraduate medical education. Our study aimed to measure
      the effect of TBL on promoting learning and teamwork in the setting of pathology
      residency training. METHODS: Four TBL sessions were held and individual and group
      readiness assurance tests (IRAT/GRATs) were performed; scores were compared using
      Wilcoxon matched-pairs signed rank tests. Residents completed 18-item validated
      team performance surveys measuring the quality of team interactions on a scale of
      0 (none of the time) to 6 (all of the time). Mean and standard deviation were
      calculated for each item. RESULTS: Scores on the IRAT vs GRAT were significantly
      different (P < .05). The team performance survey received mean scores ranging
      from 5.3 +/- 1.1 to 6.0 +/- 0.0. CONCLUSIONS: The use of TBL promotes teamwork
      and learning in a pathology residency program. Residents scored higher on the
      readiness assurance tests when working in teams, demonstrating the effectiveness
      of team learning and achievement. In addition, the Accreditation Council for
      Graduate Medical Education competencies of professionalism and interpersonal and
      communication skills were further enhanced by incorporating TBL into pathology
      residency training.

PMID- 24926083
TI  - Laboratory turnaround times in response to an abrupt increase in specimen testing
      after a natural disaster.
AB  - OBJECTIVES: Understanding how key indicators change during extreme circumstances
      could help laboratories maintain high standards when responding to disasters. We
      assessed the effects of an earthquake on turnaround times (TATs) at a hospital
      laboratory. METHODS: We examined TATs for 709,786 potassium tests and 196,795
      urine cultures from February 2010 to January 2013. Hospital and community data
      were evaluated separately and compared during the transport, registration
      (accessioning), and analysis time phases. RESULTS: After the earthquake, the
      laboratory undertook approximately 70% of the nonacute community specimen
      testing. Initially, community transport times increased by 20 to 27 hours and
      remained 2 to 3 hours above prequake levels. Registration time increased by 10 to
      20 minutes (hospital) and 30 to 45 minutes (community) for a short period. During
      the initial few months, community urine culture analysis time increased by more
      than 50 hours. CONCLUSIONS: The increase in specimen numbers affected short- and
      long-duration test TATs differently. Streamlining and automating processes
      reduced registration and analysis times. Increased transport time was outside the
      control of the laboratory.

PMID- 24926082
TI  - Evaluation of anti-PLA2R1 as measured by a novel ELISA in patients with
      idiopathic membranous nephropathy: a cohort study.
AB  - OBJECTIVES: Autoantibodies against the M-type phospholipase A2 receptor 1 (anti
      PLA2R1) have been demonstrated to be very specific for idiopathic membranous
      nephropathy (MN). We studied a novel enzyme-linked immunosorbent assay (ELISA)
      and compared results with results obtained using an indirect immunofluorescence
      (IIF) and a Western blotting test (WB). METHODS: One-hundred nine patients with
      idiopathic MN were recruited between November 1979 and March 2011. The control
      cohort comprised serum samples from patients with secondary MN (n = 16) and
      nephrotic controls (n = 17). The presence of anti-PLA2R1 in serum samples
      obtained at the time of renal biopsy was determined using ELISA, IIF, and WB.
      RESULTS: With similar specificity (>= 97%), sensitivity varied from 68% (IIF) to
      72% (ELISA, WB). Remarkably, patients who were seronegative for anti-PLA2R1 more
      often entered spontaneous remission (P = .038), whereas seropositive patients
      were more frequently treated with immunosuppressive agents (P < .001).
      CONCLUSIONS: ELISA performs excellently in differentiating idiopathic from
      secondary MN. Furthermore, ELISA shared high agreement with WB and IIF.

PMID- 24926084
TI  - Clinical performance of the BD Onclarity HPV assay using an adjudicated cohort of
      BD SurePath liquid-based cytology specimens.
AB  - OBJECTIVES: To compare the performance of the BD Onclarity HPV Assay (BD
      Diagnostics, Sparks, MD) in BD SurePath liquid-based cytology media with that of
      Hybrid Capture 2 (HC2, Qiagen, Germantown, MD) samples co-collected in specimen
      transport medium in an adjudicated patient cohort. METHODS: The performance of
      the BD Onclarity HPV Assay using BD SurePath media was compared with that of HC2
      samples co-collected in specimen transport medium using 541 archived samples from
      a multicenter US clinical trial with histologically adjudicated cervical biopsy
      specimens. RESULTS: The sensitivity for cervical intraepithelial neoplasia (CIN)
      2 positivity (n - 104) was 90.4% (95% confidence interval [CI], 83-95) and 93.3%
      (95% CI, 87-97) and specificity was 76.9% (95% CI, 73-81) and 77.8% (95% CI, 74
      82) for the BD assay and HC2, respectively. Nine cases of CIN 2+ had results
      discordant with the high-risk HPV assay. All were found to have been correctly
      classified with the BD assay using a novel WAVE denaturing high-performance
      liquid chromatography double-stranded DNA sequencing method. CONCLUSIONS: The
      clinical performance of The BD Onclarity HPV Assay with respect to histology end
      points was similar to HC2. Moreover, discordant analysis revealed improved
      performance of the BD assay with respect to ability to provide extended
      genotyping information and lack of cross-reactivity with low-risk HPV types
      associated with cellular abnormalities. The relative risks for CIN 3 disease for
      HPV 31 and HPV 33/58 (combined) were comparable to that of HPV 18 in this
      population, suggesting that these genotypes may warrant monitoring in future
      studies.

PMID- 24926086
TI  - Are amended surgical pathology reports getting to the correct responsible care
      provider?
AB  - OBJECTIVES: Amended reports (AmRs) need to follow patients to treating
      physicians, to avoid erroneous management based on the original diagnosis. This
      study was undertaken to determine if AmRs followed the patient appropriately.
      METHODS: AmRs with diagnostic changes and discrepancies between ordering and
      treating physicians were tracked. Chart reviews, electronic medical report (EMR)
      reviews, and interviews were conducted to establish receipt of the AmR by the
      correct physician. RESULTS: Seven of 60 AmRs had discrepancies between the
      ordering and treating physicians, all with malignant diagnoses. The AmR was
      present in the treating physician's chart in only one case. Ordering physicians
      indicated that AmRs were not forwarded to treating physicians when corrected
      results arrived after patient referral, under the assumption that the new
      physician was automatically forwarded pathology updates. No harm was documented
      in any of our cases. In one case with a significant amendment, the correct
      information was entered in the patient chart based on a tumor board discussion. A
      review of two electronic health record systems uncovered significant shortcomings
      in each delivery system. CONCLUSIONS: AmRs fail to follow the patient's chain of
      referrals to the correct care provider, and EMR systems lack the functionality to
      address this failure and alert clinical teams of amendments.

PMID- 24926085
TI  - APOA1 mRNA expression in ovarian serous carcinoma effusions is a marker of longer
      survival.
AB  - OBJECTIVES: We previously described the overexpression of APOA1 and GPX3 in
      ovarian/peritoneal serous carcinoma compared with breast carcinoma effusions
      using gene expression array analysis. The objective of the present study was to
      validate this finding and to analyze the association between these genes and
      clinicopathologic parameters, including survival, in advanced-stage ovarian
      serous carcinoma. METHODS: APOA1 and GPX3 mRNA expression using quantitative
      reverse transcriptase polymerase chain reaction (qRT-PCR) was analyzed in 121
      effusions (101 ovarian, 20 breast carcinomas) and 85 solid ovarian carcinoma
      specimens (43 primary carcinomas, 42 metastases). RESULTS: APOA1 and GPX3
      transcript levels were significantly higher in ovarian carcinoma at all anatomic
      sites compared with breast carcinoma effusions (P < .001). GPX3 mRNA levels were
      significantly higher in primary carcinomas and solid metastases from patients who
      received neoadjuvant chemotherapy compared with chemo-naive tumors (P = .016).
      APOA1 and GPX3 mRNA levels in the entire effusion series were unrelated to
      clinicopathologic parameters. However, higher APOA1 mRNA levels in primary
      diagnosis pre-chemotherapy effusions were significantly related to better overall
      survival (P = .045), a finding that retained its significance in Cox multivariate
      analysis (P = .016). CONCLUSIONS: APOA1 and GPX3 mRNA levels on qRT-PCR
      effectively differentiate ovarian from breast carcinoma. APOA1 may be a novel
      prognostic marker in metastatic serous carcinoma.

PMID- 24926087
TI  - Semiquantitative GATA-3 immunoreactivity in breast, bladder, gynecologic tract,
      and other cytokeratin 7-positive carcinomas.
AB  - OBJECTIVES: To evaluate GATA-3 immunohistochemical expression semiquantitatively
      in breast, gynecologic, gastric, pancreatic-biliary tract, urothelial, and
      vulvar/cervical squamous cell carcinomas. METHODS: GATA-3 expression was
      evaluated by immunohistochemistry in 198 invasive breast carcinomas on tissue
      microarrays. Tissue microarrays of other tissues included 144 gynecologic tumors,
      28 bladder carcinomas, 63 cholangiocarcinomas, 20 pancreatic carcinomas, and 62
      gastric carcinomas. Full tissue sections of 10 invasive squamous cell carcinomas
      were also stained. GATA-3 expression was semiquantitatively scored using an H
      score method. H-score greater than 10 was considered a positive result. RESULTS:
      Of 186 breast carcinomas, 95% were positive (mean H-score of 217). GATA-3
      expression was uncommon in 139 nonsquamous gynecologic tumors, with often weak
      reactivity (mean H-score <50) seen in 18% of endocervical, 7% of endometrial, and
      10% of ovarian tumors. Six (60%) of 10 squamous cell carcinomas expressed GATA-3
      (mean H-score of 102). Of 22 urothelial carcinomas, 95% expressed GATA-3 (mean H
      score of 170). A few cholangiocarcinomas (3%), pancreatic adenocarcinomas (10%),
      and gastric carcinomas (2%) weakly expressed GATA-3 (mean H-score <50).
      CONCLUSIONS: Strong GATA-3 expression is a reliable marker of primary breast
      carcinoma in the appropriate clinical context. GATA-3 reactivity in around 70% of
      triple-negative breast carcinomas is also clinically useful. Significant
      reactivity in gynecologic squamous cell carcinomas suggests that GATA-3 alone
      cannot reliably distinguish these tumors from urothelial carcinoma.

PMID- 24926088
TI  - Risk factors for quantity not sufficient sweat collection in infants 3 months or
      younger.
AB  - OBJECTIVES: The purpose is to identify demographic characteristics associated
      with a quantity not sufficient (QNS) sweat collection in infants 3 months or
      younger. METHODS: History of premature birth, infant race and sex, gestational
      age at delivery, and weight of the infant were compared with QNS collection.
      RESULTS: Of 221 sweat collections from 197 infants, 25 were QNS. Infant weight
      less than 3 kg and history of prematurity were associated with QNS collection (P
      < .001). Thirteen (30.2%) of 43 infants weighing less than 3 kg had QNS
      collections compared with 12 (7.9%) of 151 infants 3 kg or more. Twelve (46.2%)
      premature infants had QNS collections compared with 13 (7.6%) term infants. Lower
      birth gestational age and corrected gestational age were associated with QNS
      collections. Six (86%) of seven infants who weighed less than 3 kg, had a history
      of prematurity, and were more than 54 days old at testing had a QNS result. Sex
      and race did not correlate with QNS collections. CONCLUSIONS: Weight less than 3
      kg and history of prematurity are associated with an increased chance of QNS
      sweat collections.

PMID- 24926089
TI  - Relatively restricted migration of polyclonal IgG4 may mimic a monoclonal
      gammopathy in IgG4-related disease.
AB  - OBJECTIVES: IgG4-related disease (IgG4-RD) is an increasingly recognized syndrome
      of unknown etiology that can affect a wide variety of organs. The commonly shared
      features include tumor-like swelling of the involved organs, a lymphoplasmacytic
      infiltrate enriched with polyclonal IgG4-positive plasma cells, variable degree
      of fibrosis, and elevated serum concentrations of polyclonal IgG4. METHODS: In a
      qualitative retrospective study, the electrophoretic characteristics of serum
      from patients with increased polyclonal IgG4 were studied to see if a
      reproducible pattern could be identified. RESULTS: We demonstrate that a
      characteristic focal band bridging the beta and gamma fraction by serum protein
      electrophoresis may be a first serologic indication for IgG4-RD. We further
      demonstrate that significant kappa:lambda skewing can occur in the polyclonal
      IgG4 fraction. CONCLUSIONS: The focal band detected by electrophoresis in sera
      from patients with IgG4-RD can be confirmed as polyclonal by immunofixation or
      immunosubtraction. Because these bands may be predominately of one light chain
      isotype, they could be misinterpreted as monoclonal gammopathies.

PMID- 24926090
TI  - Carbonic anhydrase IX (CAIX) does not differentiate between benign and malignant
      mesothelium.
AB  - OBJECTIVES: To examine carbonic anhydrase IX (CAIX), a marker of renal cell
      carcinoma that recently has been described in malignant effusions. METHODS:
      Pleural and peritoneal fluids with the following diagnoses-reactive (n = 23),
      carcinoma (n = 17), and "suspicious for mesothelioma" (n = 4)-were immunostained
      for CAIX, calretinin, Ber-EP4, and MOC31. A tissue microarray of epithelioid (n =
      27) and sarcomatoid (n = 8) mesotheliomas and three cases of benign mesothelium
      were also immunostained for CAIX. RESULTS: Mesothelial cells in both reactive
      (18/23) and malignant effusions (18/21) were positive for CAIX (P > .05). In
      carcinomatous effusions, CAIX expression was restricted to the mesothelial cells.
      Agreement between CAIX and calretinin expression was present in 89% of cases. In
      tissues, CAIX was positive in 100% of benign and 91% of malignant mesothelium.
      CONCLUSIONS: CAIX can be a useful ancillary marker for identifying mesothelial
      cells. There is no difference in CAIX expression between benign and malignant
      mesothelium. Caution should be exercised while evaluating for metastasis from
      renal cell carcinoma.

PMID- 24926091
TI  - Utility of CD279/PD-1 immunohistochemistry in the evaluation of benign and
      neoplastic T-cell-rich bone marrow infiltrates.
AB  - OBJECTIVES: CD279 expression is used to help identify angioimmunoblastic T-cell
      lymphoma (AITL) or other T-cell lymphomas of T-follicular helper (TFH) cell
      origin; however, its utility in assessing lymphoid infiltrates in the bone marrow
      (BM) is not well established. METHODS: Immunohistochemistry for CD279 was
      performed on normal staging BM and in BM with benign lymphoid aggregates (LAs),
      AITLs, and other T-cell lymphomas. RESULTS: Seven of 10 staging BMs demonstrated
      scattered, usually weakly CD279+ cells. Thirty-four of 38 BMs had scattered
      weakly/variably intense CD279+ cells within LAs, but only four contained 11% to
      25% CD279+ cells. Three of four AITLs were strongly CD279+, but one contained
      only around 10% CD279+ cells. Eleven of the other 38 T-cell lymphomas were
      CD279+, including five possible AITLs; four peripheral T-cell lymphomas, not
      otherwise specified; and two T-cell large granular lymphocytic leukemias.
      CONCLUSIONS: Although useful in assessing selected BM lymphoid infiltrates, CD279
      expression may be limited in AITLs, is not specific for TFH lymphomas, and can be
      seen in benign lymphoid infiltrates, although without extensive strong
      positivity.

PMID- 24926092
TI  - The medium, not the message. How tattoos correlate with early mortality.
AB  - OBJECTIVES: At autopsy, tattoos are recorded as part of the external examination.
      An investigation was undertaken to determine whether negative messages that are
      tattooed on a decedent may indicate a predisposition to certain fatal outcomes.
      METHODS: Tattooed and nontattooed persons were classified by demography and
      forensics. Tattoos with negative or ominous messages were reviewed. Statistical
      comparisons were made. RESULTS: The mean age of death for tattooed persons was 39
      years, compared with 53 years for nontattooed persons (P = .0001). There was a
      significant contribution of negative messages in tattoos associated with
      nonnatural death (P = .0088) but not with natural death. However, the presence of
      any tattoo was more significant than the content of the tattoo. CONCLUSIONS:
      Persons with tattoos appear to die earlier than those without. There may be an
      epiphenomenon between having tattoos and risk-taking behavior such as drug or
      alcohol use. A negative tattoo may suggest a predisposition to violent death but
      is eclipsed by the presence of any tattoo.

PMID- 24926094
TI  - Erythrocyte fatty acids as potential biomarkers in the diagnosis of advanced lung
      adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer.
AB  - OBJECTIVES: To analyze the fatty acid profiles of erythrocyte total lipids from
      patients with advanced squamous cell lung carcinoma (SCC), lung adenocarcinoma
      (ADC), and small cell lung cancer (SCLC) and benign lung diseases (chronic
      obstructive pulmonary disease [COPD] and asthma) to reveal the fatty acids that
      could be used as lung cancer biomarkers. METHODS: Thirty, 20, 15, 17, and 19
      patients with SCC, ADC, SCLC, COPD, and asthma, respectively, and 55 healthy
      participants were enrolled in our study. Fatty acid profiles were investigated
      using gas chromatography/mass spectrometry followed by receiver operating
      characteristic (ROC) curve analysis. Sialic acid (SA) and cytokeratins were
      measured by the thiobarbituric acid and immunoradiometric methods, respectively.
      RESULTS: At least one of the main fatty acids might be used as a biomarker for
      every type of lung cancer: arachidonic (20:4n6), linoleic (18:2n6), and stearic
      (18:0) acids for ADC, SCC, and SCLC, respectively. These fatty acids showed
      diagnostic yields and operating characteristics similar to or higher than the
      commonly used SA or cytokeratin markers. CONCLUSIONS: Fatty acids from
      erythrocyte total lipids might be used as diagnostic biomarkers of lung ADC, SCC,
      and SCLC. Their use in different aspects of the disease process needs to be
      explored.

PMID- 24926093
TI  - Assessment of correlation between p16INK4a staining, specific subtype of human
      papillomavirus, and progression of LSIL/CIN1 lesions: first comparative study.
AB  - OBJECTIVES: To study and compare the effectiveness of p16(INK4a) staining and
      specific human papillomavirus (HPV) subtypes as a prognostic marker in cervical
      intraepithelial neoplasia grade 1 (CIN1; low-grade squamous intraepithelial
      lesions). METHODS: Sixty-four cervical samples diagnosed as CIN1 and stained with
      p16(INK4a), with HPV status assessed by polymerase chain reaction-direct
      sequencing. RESULTS: Of the 34 p16(INK4a)-negative biopsy specimens, 26
      regressed, seven persisted, and one progressed. Of the 20 p16(INK4a) diffusely
      positive biopsy specimens, seven regressed, eight persisted, and five progressed.
      Ten biopsy specimens stained positive only in the lower one-third of the sample,
      of which seven regressed and three persisted. p16(INK4a) diffusely positive CIN1
      lesions were associated with only high-risk HPV subtypes, with the exception of
      one HPV-negative biopsy specimen. Three different high-risk HPV subtypes and one
      low-risk HPV subtype (HPV66) were identified in the six CIN1 lesions that
      progressed. CONCLUSIONS: There is a significant relationship between p16(INK4a)
      immunostaining and follow-up (P = .002). p16(INK4a)-negative specimens or
      positivity in the lower one-third of CIN1 lesions seldom progress to a CIN2-3
      lesion.

PMID- 24926095
TI  - High expression of the mismatch repair protein MSH6 is associated with poor
      patient survival in melanoma.
AB  - OBJECTIVES: The outcome of patients with primary melanoma (PM) cannot be
      completely explained based on currently adopted clinical-histopathologic
      criteria. In this study, we evaluated the potential prognostic value of mismatch
      repair protein expression in PMs. METHODS: We examined the immunohistochemical
      staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs
      and investigated their association with tumor clinicopathologic variables and
      melanoma mortality. RESULTS: Expression of MSH2, MLH1, and PMS2 was high in
      benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was
      absent or extremely low in benign nevi and increased in a subset of PMs. In the
      multivariate analysis, including sex, age, Breslow thickness, and ulceration,
      high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was
      significantly associated with an increased risk of melanoma mortality (relative
      risk, 3.76; 95% confidence interval, 1.12-12.70). CONCLUSIONS: MSH6 protein
      expression can be a valuable marker to improve prognosis assessment in PMs.

PMID- 24926098
TI  - A bisected pupil for studying single-molecule orientational dynamics and its
      application to three-dimensional super-resolution microscopy.
AB  - A phase mask design that we term a "bisected pupil" (BSP) provides several
      advantages for single-molecule optical imaging. When using the BSP with a dual
      polarization optical Fourier processing system, both the position and dipole
      orientation of individual fluorescent molecules may be measured from a single
      camera image. In the context of single-molecule super-resolution microscopy, this
      technique permits one to diagnose, and subsequently to remove imaging artifacts
      resulting from orientation-induced localization errors. If the molecules labeling
      a structure are rotationally mobile, thus mitigating dipole orientation errors,
      this technique enables super-resolution imaging in three dimensions. We present
      simulations and experimental verification.

PMID- 24926097
TI  - Analysis of ultra-high sensitivity configuration in chip-integrated photonic
      crystal microcavity bio-sensors.
AB  - We analyze the contributions of quality factor, fill fraction, and group index of
      chip-integrated resonance microcavity devices, to the detection limit for bulk
      chemical sensing and the minimum detectable biomolecule concentration in
      biosensing. We analyze the contributions from analyte absorbance, as well as from
      temperature and spectral noise. Slow light in two-dimensional photonic crystals
      provide opportunities for significant reduction of the detection limit below 1 *
      10-7 RIU (refractive index unit) which can enable highly sensitive sensors in
      diverse application areas. We demonstrate experimentally detected concentration
      of 1 fM (67 fg/ml) for the binding between biotin and avidin, the lowest reported
      till date.

PMID- 24926099
TI  - Extraction of diffuse correlation spectroscopy flow index by integration of Nth
      order linear model with Monte Carlo simulation.
AB  - Conventional semi-infinite solution for extracting blood flow index (BFI) from
      diffuse correlation spectroscopy (DCS) measurements may cause errors in
      estimation of BFI (alphaDB ) in tissues with small volume and large curvature. We
      proposed an algorithm integrating Nth-order linear model of autocorrelation
      function with the Monte Carlo simulation of photon migrations in tissue for the
      extraction of alphaDB . The volume and geometry of the measured tissue were
      incorporated in the Monte Carlo simulation, which overcome the semi-infinite
      restrictions. The algorithm was tested using computer simulations on four tissue
      models with varied volumes/geometries and applied on an in vivo stroke model of
      mouse. Computer simulations shows that the high-order (N >= 5) linear algorithm
      was more accurate in extracting alphaDB (errors < +/-2%) from the noise-free DCS
      data than the semi-infinite solution (errors: -5.3% to -18.0%) for different
      tissue models. Although adding random noises to DCS data resulted in alphaDB
      variations, the mean values of errors in extracting alphaDB were similar to those
      reconstructed from the noise-free DCS data. In addition, the errors in extracting
      the relative changes of alphaDB using both linear algorithm and semi-infinite
      solution were fairly small (errors < +/-2.0%) and did not rely on the tissue
      volume/geometry. The experimental results from the in vivo stroke mice agreed
      with those in simulations, demonstrating the robustness of the linear algorithm.
      DCS with the high-order linear algorithm shows the potential for the inter
      subject comparison and longitudinal monitoring of absolute BFI in a variety of
      tissues/organs with different volumes/geometries.

PMID- 24926100
TI  - Strategic sophistication of individuals and teams. Experimental evidence.
AB  - Many important decisions require strategic sophistication. We examine
      experimentally whether teams act more strategically than individuals. We let
      individuals and teams make choices in simple games, and also elicit first- and
      second-order beliefs. We find that teams play the Nash equilibrium strategy
      significantly more often, and their choices are more often a best response to
      stated first order beliefs. Distributional preferences make equilibrium play less
      likely. Using a mixture model, the estimated probability to play strategically is
      62% for teams, but only 40% for individuals. A model of noisy introspection
      reveals that teams differ from individuals in higher order beliefs.

PMID- 24926101
TI  - Lead-free solder alloys: Thermodynamic properties of the (Au + Sb + Sn) and the
      (Au + Sb) system.
AB  - The thermodynamic properties of liquid (Au-Sb-Sn) alloys were studied with an
      electromotive force (EMF) method using the eutectic mixture of KCl/LiCl with
      addition of SnCl2 as a liquid electrolyte. Activities of Sn in the liquid alloys
      were measured at three cross-sections with constant molar ratios of Au:Sb = 2:1,
      1:1, and 1:2 with tin in the concentration range between 5 at.% and 90 at.% from
      the liquidus of the samples up to 1073 K. The integral Gibbs excess energies and
      the integral enthalpies at 873 K were calculated by Gibbs-Duhem integration.
      Additionally liquid Au-Sb alloys have been measured at 913 K with the EMF method
      as no reliable data for the Gibbs excess energies have been found in literature.
      The eutectic mixture of KCl/LiCl with addition of SbCl3 has been used as an
      electrolyte for the measurements. The Gibbs excess energies from the (Au + Sb)
      system were necessary for the integration of the thermodynamic properties of the
      ternary (Au + Sb + Sn) system.

PMID- 24926102
TI  - Calorimetric study of the entropy relation in the NaCl-KCl system.
AB  - The heat capacity of one Na-rich and two K-rich samples of the NaCl-KCl (halite
      sylvite) crystalline solution was investigated between 5 and 300 K. It deviated
      positively from ideal behaviour with a maximum at 40 K. The thereby produced
      excess entropy at 298.15 K was described by a symmetric Margules mixing model
      yielding [Formula: see text] = 8.73 J/mol/K. Using enthalpy of mixing data from
      the literature and our data on the entropy, the solvus was calculated for a
      pressure of 105 Pa and compared with the directly determined solvus. The
      difference between them can be attributed to the effect of Na-K short range
      ordering (clustering).

PMID- 24926103
TI  - The vibrational and configurational entropy of alpha-brass.
AB  - The heat capacities of two samples of a fcc Cu-Zn alloy with the composition
      CuZn15 and CuZn34 were measured from T = 5 K to 573 K using relaxation and
      differential scanning calorimetry. Below ~90 K, they are characterised by
      negative excess heat capacities deviating from ideal mixing by up to -0.20 and 
      0.44 J . mol-1 . K-1 for CuZn15 and CuZn34, respectively. The excess heat
      capacities produce excess vibrational entropies, which are less negative compared
      to the excess entropy available from the literature. Since the literature entropy
      data contain both, the configurational and the vibrational part of the entropy,
      the difference is attributed to the excess configurational entropy. The
      thermodynamics of different short-range ordered samples was also investigated.
      The extent of the short-range order had no influence on the heat capacity below T
      = 300 K. Above T = 300 K, where the ordering changed during the measurement, the
      heat capacity depended strongly on the thermal history of the samples. From these
      data, the heat and entropy of ordering was calculated. The results on the
      vibrational entropy of this study were also used to test a relationship for
      estimating the excess vibrational entropy of mixing.

PMID- 24926104
TI  - On Ramsey's conjecture.
AB  - Studying a one-sector economy populated by finitely many heterogeneous households
      that are subject to no-borrowing constraints, we confirm a conjecture by Frank P.
      Ramsey according to which, in the long run, society would be divided into the set
      of patient households who own the entire capital stock and impatient ones without
      any physical wealth. More specifically, we prove (i) that there exists a unique
      steady state equilibrium that is globally asymptotically stable and (ii) that
      along every equilibrium the most patient household owns the entire capital of the
      economy after some finite time. Furthermore, we prove that despite the presence
      of the no-borrowing constraints all equilibria are efficient. Our results are
      derived for the continuous-time formulation of the model that was originally used
      by Ramsey, and they stand in stark contrast to results that - over the last three
      decades - have been found in the discrete-time version of the model.

PMID- 24926105
TI  - Amos-type bounds for modified Bessel function ratios.
AB  - We systematically investigate lower and upper bounds for the modified Bessel
      function ratio [Formula: see text] by functions of the form [Formula: see text]
      in case [Formula: see text] is positive for all [Formula: see text], or
      equivalently, where [Formula: see text] or [Formula: see text] is a negative
      integer. For [Formula: see text], we give an explicit description of the set of
      lower bounds and show that it has a greatest element. We also characterize the
      set of upper bounds and its minimal elements. If [Formula: see text], the minimal
      elements are tangent to [Formula: see text] in exactly one point [Formula: see
      text], and have [Formula: see text] as their lower envelope. We also provide a
      new family of explicitly computable upper bounds. Finally, if [Formula: see text]
      is a negative integer, we explicitly describe the sets of lower and upper bounds,
      and give their greatest and least elements, respectively.

PMID- 24926106
TI  - On Components, Latent Variables, PLS and Simple Methods: Reactions to Rigdon's
      Rethinking of PLS.
AB  - Rigdon (2012) suggests that partial least squares (PLS) can be improved by
      killing it, that is, by making it into a different methodology based on
      components. We provide some history on problems with component-type methods and
      develop some implications of Rigdon's suggestion. It seems more appropriate to
      maintain and improve PLS as far as possible, but also to freely utilize
      alternative models and methods when those are more relevant in certain data
      analytic situations. Huang's (2013) new consistent and efficient PLSe2
      methodology is suggested as a candidate for an improved PLS.

PMID- 24926107
TI  - Aponogeton pollen from the Cretaceous and Paleogene of North America and West
      Greenland: Implications for the origin and palaeobiogeography of the genus.
AB  - The fossil record of Aponogeton (Aponogetonaceae) is scarce and the few reported
      macrofossil findings are in need of taxonomic revision. Aponogeton pollen is
      highly diagnostic and when studied with light microscopy (LM) and scanning
      electron microscopy (SEM) it cannot be confused with any other pollen types. The
      fossil Aponogeton pollen described here represent the first reliable Cretaceous
      and Eocene records of this genus worldwide. Today, Aponogeton is confined to the
      tropics and subtropics of the Old World, but the new fossil records show that
      during the late Cretaceous and early Cenozoic it was thriving in North America
      and Greenland. The late Cretaceous pollen record provides important data for
      future phylogenetic and phylogeographic studies focusing on basal monocots,
      especially the Alismatales. The Eocene pollen morphotypes from North America and
      Greenland differ in morphology from each other and also from the older Late
      Cretaceous North American pollen morphotype, indicating evolutionary trends and
      diversification within the genus over that time period. The presence of
      Aponogeton in the fossil record of North America and Greenland calls for a
      reconsideration of all previous ideas about the biogeographic history of the
      family.

PMID- 24926108
TI  - Concise Synthesis of Functionalized Benzocyclobutenones.
AB  - A concise approach to access functionalized benzocyclobutenones from 3-halophenol
      derivatives is described. This modified synthesis employs a [2+2] cycloaddition
      between benzynes generated from dehydrohalogenation of aryl halides using LiTMP
      and acetaldehyde enolate generated from n-BuLi and THF, followed by oxidation of
      the benzocyclobutenol intermediates to provide benzocyclobutenones. The [2+2]
      reaction can be run on a 10-gram scale with an increased yield. A number of
      functional groups including alkenes and alkynes are tolerated. Coupling of
      benzynes with ketene silyl acetals to give 8-substituted benzocyclobutenones is
      also demonstrated.

PMID- 24926109
TI  - A novel route to organonitrites by Pd-catalyzed cross-coupling of sodium nitrite
      and potassium organotrifluoroborates.
AB  - Microwave irradiated palladium-catalyzed cross-coupling reaction of potassium
      styryltrifluoroborates and sodium nitrite gives the corresponding styryl nitrites
      in high yields. Potassium aryltrifluoroborates also furnish aryl nitrites under
      same reaction condition. This unprecedented cross-coupling is an interesting
      development and has the potential to lead to new nitration protocols.

PMID- 24926110
TI  - "Translating" between survey answer formats.
AB  - Survey research remains the most popular source of market knowledge, yet
      researchers have not yet established one consistent technique for measuring
      responses. Some market research companies offer respondents two answer options;
      others five or seven. Some answer formats use middle points on the answer scales,
      others do not. Some formats verbalize all answer options, some only the
      endpoints. The wide variety of answer formats that market research companies and
      academic researchers use makes comparing results across studies virtually
      impossible. This study offers guidance for market researchers by presenting
      empirical translations for the answer formats they most commonly use, thus
      enabling easier comparisons of results.

PMID- 24926111
TI  - Risk-taking in social settings: Group and peer effects.
AB  - We investigate experimentally the effect of consultation (unincentivized advice)
      on choices under risk in an incentivized investment task. We compare consultation
      to two benchmark treatments: one with isolated individual choices, and a second
      with group choice after communication. Our benchmark treatments replicate
      findings that groups take more risk than individuals in the investment task;
      content analysis of group discussions reveals that higher risk-taking in groups
      is positively correlated with mentions of expected value. In our consultation
      treatments, we find evidence of peer effects: decisions within the peer group are
      significantly correlated. However, average risk-taking after consultation is not
      significantly different from isolated individual choices. We also find that risk
      taking after consultation is not affected by adding a feedback stage in which
      subjects see the choices of their consultation peers.

PMID- 24926112
TI  - Economic probes of mental function and the extraction of computational
      phenotypes.
AB  - Economic games are now routinely used to characterize human cognition across
      multiple dimensions. These games allow for effective computational modeling of
      mental function because they typically come equipped with notions of optimal
      play, which provide quantitatively prescribed target functions that can be
      tracked throughout an experiment. The combination of these games, computational
      models, and neuroimaging tools open up the possibility for new ways to
      characterize normal cognition and associated brain function. We propose that
      these tools may also be used to characterize mental dysfunction, such as that
      found in a range of psychiatric illnesses. We describe early efforts using a
      multi-round trust game to probe brain responses associated with healthy social
      exchange and review how this game has provided a novel and useful
      characterization of autism spectrum disorder. Lastly, we use the multi-round
      trust game as an example to discuss how these kinds of games could produce novel
      bases for representing healthy behavior and brain function and thus provide
      objectively identifiable subtypes within a broad spectrum of mental function.

PMID- 24926113
TI  - Individual based and mean-field modeling of direct aggregation.
AB  - We introduce two models of biological aggregation, based on randomly moving
      particles with individual stochasticity depending on the perceived average
      population density in their neighborhood. In the first-order model the location
      of each individual is subject to a density-dependent random walk, while in the
      second-order model the density-dependent random walk acts on the velocity
      variable, together with a density-dependent damping term. The main novelty of our
      models is that we do not assume any explicit aggregative force acting on the
      individuals; instead, aggregation is obtained exclusively by reducing the
      individual stochasticity in response to higher perceived density. We formally
      derive the corresponding mean-field limits, leading to nonlocal degenerate
      diffusions. Then, we carry out the mathematical analysis of the first-order
      model, in particular, we prove the existence of weak solutions and show that it
      allows for measure-valued steady states. We also perform linear stability
      analysis and identify conditions for pattern formation. Moreover, we discuss the
      role of the nonlocality for well-posedness of the first-order model. Finally, we
      present results of numerical simulations for both the first- and second-order
      model on the individual-based and continuum levels of description.

PMID- 24926114
TI  - Accurate Prediction of Stress in Fibers with Distributed Orientations Using
      Generalized High-Order Structure Tensors.
AB  - The orientation of collagen fibers plays an important role on the mechanics of
      connective tissues. Connective tissues have fibers with different orientation
      distributions. The angular integration formulation used to model the mechanics of
      fibers with distributed orientation is accurate, but computationally expensive
      for numerical methods such as finite elements. This study presents a formulation
      based on pre-integrated Generalized High-Order Structure Tensors (GHOST) which
      greatly improves the accuracy of the predicted stress. Simplifications of the
      GHOST formulation for transversely-isotropic and planar fiber distributions are
      also presented. Additionally, the GHOST and the angular integration formulations
      are compared for different loading conditions, fiber orientation functions,
      strain energy functions and degrees of fiber non-linearity. It was found that the
      GHOST formulation predicted the stress of the fibers with an error lower than 10%
      for uniaxial and biaxial tension. Fiber non-linearity increased the error of the
      GHOST formulation; however, the error was reduced to negligible values by
      considering higher order structure tensors. The GHOST formulation produced lower
      errors when used with an elliptical fiber density function and a binomial strain
      energy function. In conclusion, the GHOST formulation is able to accurately
      predict the stress of fibers with distributed orientation without requiring
      numerous integral calculations. Consequently, the GHOST formulation may reduce
      the computational effort needed to analyze the mechanics of fibrous tissues with
      distributed orientations.

PMID- 24926115
TI  - European Union energy policy integration: A case of European Commission policy
      entrepreneurship and increasing supranationalism.
AB  - Focusing on gas, this article explores the role of the European Commission in the
      process of European Union energy security policy development, and the extent to
      which the policy area is becoming increasingly supranational. Situating the
      article within the literature on agenda-setting and framing, it is argued that a
      policy window was opened as a result of: enlargement to include more energy
      import dependent states, a trend of increasing energy imports and prices, and gas
      supply disruptions. From the mid-2000s, the Commission contributed to a shift in
      political norms, successfully framing import dependency as a problem requiring an
      EU-level solution, based on the institution's pre-existing preferences for a
      diversified energy supply and internal energy market. Whilst Member States retain
      significant sovereignty, the Commission has achieved since 2006 creeping
      competencies in the internal, and to a lesser extent external, dimensions of EU
      energy policy.

PMID- 24926116
TI  - Barriers and incentives to the production of bioethanol from cereal straw: A farm
      business perspective.
AB  - The EU renewable energy directive stipulates a requirement for 10% of transport
      fuels to be derived from renewable sources by 2020. Second generation biofuels
      offer potential to contribute towards this target with cereal straw representing
      a potentially large feedstock source. From an on-farm survey of 240 arable
      farmers, timeliness of crop establishment and benefits of nutrient retention from
      straw incorporation were cited as reasons for straw incorporation. However, two
      thirds (one-third) of farmers would supply wheat (barley) straw for bioenergy.
      The most popular contract length and continuous length of straw supply was either
      1 or 3 years. Contracts stipulating a fixed area of straw supply for a fixed
      price were the most frequently cited preferences, with L50 t-1 the most
      frequently cited minimum contract price that farmers would find acceptable.
      Arable farmers in England would be willing to sell 2.52 Mt of cereal straw for
      bioenergy purposes nationally and 1.65 Mt in the main cereal growing areas of
      Eastern England. Cereal straw would be diverted from current markets or on-farm
      uses and from straw currently incorporated into soil. Policy interventions may be
      required to incentivise farmers to engage in this market, but food and fuel
      policies must increasingly be integrated to meet societal goals.

PMID- 24926117
TI  - Lessons from first generation biofuels and implications for the sustainability
      appraisal of second generation biofuels.
AB  - AIMS: The emergence of second generation (2G) biofuels is widely seen as a
      sustainable response to the increasing controversy surrounding the first
      generation (1G). Yet, sustainability credentials of 2G biofuels are also being
      questioned. Drawing on work in Science and Technology Studies, we argue that
      controversies help focus attention on key, often value-related questions that
      need to be posed to address broader societal concerns. This paper examines
      lessons drawn from the 1G controversy to assess implications for the
      sustainability appraisal of 2G biofuels. SCOPE: We present an overview of key 1G
      sustainability challenges, assess their relevance for 2G, and highlight the
      challenges for policy in managing the transition. We address limitations of
      existing sustainability assessments by exploring where challenges might emerge
      across the whole system of bioenergy and the wider context of the social system
      in which bioenergy research and policy are done. CONCLUSIONS: Key lessons arising
      from 1G are potentially relevant to the sustainability appraisal of 2G biofuels
      depending on the particular circumstances or conditions under which 2G is
      introduced. We conclude that sustainability challenges commonly categorised as
      either economic, environmental or social are, in reality, more complexly
      interconnected (so that an artificial separation of these categories is
      problematic).

PMID- 24926118
TI  - Sub-lethal metal stress response of larvae of Aedes aegypti.
AB  - Aedes aegypti (Diptera: Culicidae) has adapted to urban environments; the
      urbanisation process provides suitable habitats for this disease vector
      subsequently increasing the probability of the transmission of pathogens in high
      density environments. Urban environments provide metal stressed larval habitats.
      However, little is known about the physiological cost of metal stress or how this
      might affect the performance of this mosquito species. This study aims to
      characterise the sub-lethal physiological consequences of metal stress in Aedes
      aegypti. Various parameters of mosquito physiology under larval metal stress are
      assessed including larval metallothionein expression and the effects of larval
      metal stress on adult performance and their progeny. Results show that
      environmentally relevant larval metal stress compromises larval and adult
      development and performance, and results in larval metal tolerance along with an
      increase in lipid consumption. These performance costs are coupled to a dramatic
      increase in metallothionein expression in the midgut. Metal stress results in
      lowered adult body mass and neutral storage lipids at emergence, starvation
      tolerance, fecundity and starvation tolerance of offspring compared to non-metal
      stressed individuals. Ironically, larval metal stress results in increased adult
      longevity. Together, these findings indicate that even low levels of
      environmentally relevant larval metal stress have considerable physiological
      consequences for this important disease vector.

PMID- 24926119
TI  - Biomechanical analysis of stair descent in patients with knee osteoarthritis.
AB  - [Purpose] The purposes of this study were to investigate the lower extremity
      joint kinematics and kinetics of patients with the knee osteoarthritis (knee OA)
      during stair descent and clarify the biomechanical factors related to their
      difficulty in stair descent. [Subjects and Methods] Eight healthy elderly persons
      and four knee OA patients participated in this study. A 3-D motion analysis
      system and force plates were employed to measure lower extremity joint angles,
      ranges of motion, joint moments, joint powers, and ratios of contribution for the
      joint powers while descending stairs. [Results] Knee joint flexion angle,
      extension moment, and negative power during the early stance phase in the knee OA
      group were smaller than those in the healthy subjects group. However, no
      significant changes in these parameters in the ankle joint were observed between
      the two subject groups. [Conclusion] Knee OA patients could not use the knee
      joint to absorb impact during the early stance phase of stair descent. Hence,
      they might compensate for the roles played by the intact knee joint by mainly
      using ipsilateral ankle kinematics and kinetics. 

PMID- 24926120
TI  - The influence of neuromuscular electrical stimulation on the heart rate
      variability in healthy subjects.
AB  - [Purpose] The purpose of this study was to examine the effect of neuromuscular
      electrical stimulation (NMES) on heart rate variability (HRV). [Subjects and
      Methods] Ten healthy subjects participated in the study. All subjects received
      NMES with a pulse duration of 300 us and frequency of 30 Hz at the vastus
      lateralis and vastus medialis for 15 minutes. The stimulation intensity was
      adjusted in the range of 20 to 30 mA. HRV using a pulse oximeter was measured in
      the sitting position before and after NMES. [Results] After the NMES, all HRV
      data slightly increased, but there was no significance between before and after
      data. [Conclusion] We suggest that strengthening exercises using NMES may be
      undertaken safely. 

PMID- 24926121
TI  - Effect of Togu-exercise on Lumbar Back Strength of Women with Chronic Low Back
      Pain.
AB  - [Purpose] The present study analyzed the effect of the Togu exercise program on
      the lumbar back strength of middle-aged women who did not perform regular
      exercise, and presents an effective exercise method for middle-aged women with
      chronic low back pain symptom. [Subjects] The subjects were 16 women with chronic
      low back pain attending N University, Chungcheong-do, Korea. [Methods] Height,
      weight, body fat, and body mass index (BMI) were measured using a body
      composition analyzer (Inbody 720, Biospace, Korea), which utilizes bioelectrical
      impedance analysis. Using isokinetic lumbar muscle strength measurement equipment
      [Isomed 2000, Back system, (Germany)], peak torque/body weight, total work and
      average power of flexion and extension of the lumbar region were measured. For
      lumbar stabilization exercises, an air cushion (Germany), jumper (Germany), and
      aero step (Germany) were employed. First, warm-up exercise was conducted for 10
      minutes, followed by 10 sets of the 3 main exercises using the above tools with
      10-second rest intervals. The main exercise was done for 40 minutes in total.
      [Results] The paired sample t-test showed significant in the Togu exercise group
      peak torque of flexion, peak torque of extension, total work of flexion, total
      work of extension, average power of flexion, average power of extension, after
      the exercise showed a significant difference in the Togu exercise group.
      [Conclusion] The trunk muscle actiation program for middle-aged women had a
      significant effect on muscle strength and low back pain. Therefore the trunk
      muscle activation program is effective at increasing muscular strength of middle
      aged women, and the results suggest improve muscle strength is effectively
      stabilizaties the lumbar region. 

PMID- 24926122
TI  - Correlation of the Y-Balance Test with Lower-limb Strength of Adult Women.
AB  - [Purpose] The purpose of this study was to elucidate the relationship between Y
      balance test (YBT) distance and the lower-limb strength of adult women.
      [Subjects] Forty women aged 45 to 80 years volunteered for this study. [Methods]
      The participants were tested for maximal muscle strength of the lower limbs (hip
      extensors, hip flexors, hip abductors, knee extensors, knee flexors, and ankle
      dorsiflexors) and YBT distances in the anterior, posteromedial, and
      posterolateral directions. Pearson's correlation coefficient was used to quantify
      the linear relationships between YBT distances and lower-limb strength. [Results]
      Hip extensor and knee flexor strength were positively correlated with YBT
      anterior distance. Hip extensor, hip abductor, and knee flexor strength were
      positively correlated with the YBT posteromedial distance. Hip extensor and knee
      flexor strength were positively correlated with YBT posterolateral distance.
      [Conclusion] There was a weak correlation between lower-limb strength (hip
      extensors, hip abductors, and knee flexors) and dynamic postural control as
      measured by the YBT. 

PMID- 24926123
TI  - Effect of Exercise Speed and Isokinetic Feedback on the Middle and Lower Serratus
      Anterior Muscles during Push-up Exercises.
AB  - [Purpose] This study assessed the use of different exercise speeds and isokinetic
      feedback on the middle and lower serratus anterior muscles during push-up
      exercises. [Subjects] Ten male workers voluntarily consented to participate in
      the study. [Methods] The subjects performed push-up exercises under three
      conditions. Surface electrodes were placed on the dominant right side of the
      middle and lower serratus anterior muscles. [Results] The middle and lower SA
      muscle activities under condition 2 were significantly decreased when compared
      with those under conditions 1 and 3. The middle SA activity under condition 3 was
      significantly increased when compared with that under condition 1. [Conclusion]
      This study suggests that proper selection of push-up exercise speed may be
      necessary for selective strengthening of the SA and that isokinetic feedback
      information obtained using an accelerator can help in selective strengthening of
      the middle SA. 

PMID- 24926124
TI  - Pulsed and Continuous Ultrasound Increase Chondrogenesis through the Increase of
      Heat Shock Protein 70 Expression in Rat Articular Cartilage.
AB  - [Purpose] The present study was aimed to investigate the effects of pulsed and
      continuous ultrasound (US) irradiation on heat shock protein (HSP) 70 and mRNA
      levels of chondrogenesis-related gene expression in rat tibial articular
      cartilage. [Subjects and Methods] Forty-eight rats with body weights of 200-250 g
      were randomly divided into three groups. In the control (CON) group, three rats
      were treated with sham sonication. The pulsed US irradiation group was irradiated
      with a pulse rate of 20%, a frequency of 1 MHz, and an intensity of 1.5 W/cm(2)
      for 10 minutes. The continuous US irradiation group was continuously with a
      frequency of 1 MHz and an intensity of 1.5 W/cm(2) for 10 minutes.
      Immunohistochemistry for evaluation of HSP 70 and RT-PCR for expression of the
      chondrogenesis-related mRNA were used. [Results] The expression of HSP70 protein
      was increased in the pulsed and continuous US groups. The increase in the
      continuous US group was more prominent than in the pulsed US group. In addition,
      pulsed and continuous US irradiation increased the expression of Mustn1 and Sox9.
      [Conclusion] The results of this study show that US increases chondrogenesis via
      the increase of HSP 70 and chondrogenesis-related mRNA expressions in rat
      articular cartilage. 

PMID- 24926125
TI  - Effects of a Community-based Fall Prevention Exercise Program on Activity
      Participation.
AB  - This study was conducted to identify the effects of a fall-prevention exercise
      program on the participation and static balance of elderly persons in daily life
      roles. [Subjects] Ten participants over 65 years of age (75.29+/-2.93) who were
      healthy community-dwellers (two men and eight women) were recruited. [Methods]
      The participants exercised three times a week for eight weeks. The exercise
      program was based on the fitness and mobility exercise (FAME) protocol. The
      outcome measures were changes in activity participation level and the fall index.
      [Results] After the exercise, the activity participation level significantly
      increased, and the fall index significantly decreased. [Conclusion] A fall
      prevention exercise program can have a positive effect on participation and
      static balance in older adults. 

PMID- 24926126
TI  - Effects of sling exercise therapy on trunk muscle activation and balance in
      chronic hemiplegic patients.
AB  - Weakening of trunk muscles in stroke patients hinders functional ability, safety
      and balance. To confirm whether strengthening trunk muscles could facilitate
      rehabilitation of stroke patients, we investigated the effectiveness of sling
      exercise therapy (SET) using closed kinetic chain exercises to activate trunk
      muscles and improve balance in stroke patients. [Subjects and Methods] Twenty
      stroke patients with chronic hemiplegia were equally divided into 2 groups, a SET
      group and a control group that performed regular exercises on a mat with the
      assistance of a table. Patients in both groups exercised for 30 min, three times
      per week for 4 weeks. Trunk muscle activity was measured using surface
      electromyography, whereas balance was measured using the Berg Balance Scale,
      Frailty and Injuries Cooperative Studies of Intervention Technique, Timed Up & Go
      test, and BioRescue before and after the 4-week experimental period. [Results]
      Trunk muscle activity and balance before and after intervention in both groups
      were significantly different. However, no significant differences were observed
      between the 2 groups. [Conclusion] Although SET was not more effective than
      regular exercise, significant improvement was observed before and after SET.
      Therefore, SET can be considered effective in strengthening trunk muscles in
      stroke patients with chronic hemiplegia. 

PMID- 24926127
TI  - Relationship between Lower Extremity Tightness and Star Excursion Balance Test
      Performance in Junior High School Baseball Players.
AB  - [Purpose] The purpose of this study was to examine the relationship between lower
      extremity tightness and lower extremity balance, measured by the Star Excursion
      Balance Test (SEBT), in junior high school baseball players. [Subjects] Thirty
      three male students belonging to baseball clubs in 2 junior high schools
      participated in this study. [Methods] For the SEBT, we chose to examine the
      anterior (ANT), posterior (POS), lateral (LAT), and medial (MED) directions.
      Regarding muscle tightness measurement, the angle of each joint of the bilateral
      iliopsoas, quadriceps, hamstring, gastrocnemius, hip internal rotator, and hip
      external rotator was measured. [Results] The ANT direction of the SEBT was
      significantly negatively correlated with gastrocnemius tightness. The MED
      direction of the SEBT was significantly positively correlated with hip internal
      rotator tightness and hamstrings tightness and significantly negatively
      correlated with gastrocnemius tightness. The LAT direction of the SEBT was
      significantly negatively correlated with iliopsoas tightness and gastrocnemius
      tightness. [Conclusion] Since the rate of upper extremity injury is high in these
      subjects and this could be due to tightness and instability of the lower
      extremity from a kinetic viewpoint, the SEBT could be used as a standard
      evaluation test when examining upper extremity injuries in young baseball
      players. 

PMID- 24926128
TI  - Prevalence of Work-related Musculoskeletal Symptoms and Their Associations with
      Job Stress in Female Caregivers Living in South Korea.
AB  - [Purpose] The purpose of this study was to assess the work-related
      musculoskeletal system symptoms and the extent of job stress in female
      caregivers, as well as the interrelationship between these factors. [Subjects and
      Methods] Korea Occupational Safety and Health Agency (KOSHA) Code H-43 of the
      Guidelines for the Examination of Elements Harmful to the Musculoskeletal System
      was used as a tool to measure musculoskeletal symptoms. Caregiver job stress was
      assessed from the Korean Occupational Stress Scale short form. [Results] The
      level of symptoms in the hand/wrist/finger and leg/foot regions had some relation
      to job stress. Job stress scores were mainly shown to be high when pain was
      reported. On the other hand, it was shown that the degree of musculoskeletal
      symptoms by body part was unrelated to conflicts in relationships, job
      instability, or workplace culture. [Conclusion] As for the correlations between
      musculoskeletal symptoms and job stress, it was shown that as job requirements
      increased, most musculoskeletal symptoms also increased. 

PMID- 24926129
TI  - Effect of muscle vibration on spatiotemporal gait parameters in patients with
      Parkinson's disease.
AB  - [Purpose] The purpose of this study was to investigate the effect of muscle
      vibration in the lower extremities in patients with Parkinson's disease (PD)
      during walking. [Subjects] Nine patients with PD participated in this study and
      were tested with and without vibration (vibration at 60 Hz). [Methods] Eight
      oscillators of vibration were attached to the muscle bellies (tibialis anterior,
      gastrocnemius, biceps femoris, and rectus femoris) on both sides of the lower
      extremities with adhesive tape in this study. Spatiotemporal gait parameters were
      measured using a motion analysis system. [Results] Stride length and walking
      speed with vibration were significantly increased compared with those without
      vibration in PD patients. [Conclusion] These results suggest that the application
      of vibration to lower extremity muscles in patients with PD may improve the
      parkinsonian gait pattern. 

PMID- 24926130
TI  - The Effects on Muscle Activation of Flatfoot during Gait According to the
      Velocity on an Ascending Slope.
AB  - [Purpose] This study determined the difference between flatfeet and normal feet
      in humans on an ascending slope using electromyography (EMG). [Subjects] This
      study was conducted on 30 adults having normal feet (n=15) and flatfeet (n=15),
      all of whom were 21 to 30 years old. [Methods] A treadmill (AC5000M, SCIFIT,) was
      used to analyze kinematic features during gait. These features were analyzed at
      slow, normal, and fast gait velocities on an ascending slope. A surface
      electromyogram (TeleMyo 2400T, Noraxon Co., USA) was used to measure muscle
      activity changes. [Results] The activities of most muscles in the subjects with
      flatfeet were significantly different from the muscle activities in the subjects
      with normal feet at different gait velocities on an ascending slope. There were
      significant differences in the vastus medialis and abductor hallucis muscles.
      [Conclusion] Because muscle activation of the vastus medialis in relation to
      stability of the lower extremity has a tendency to increase with an increase in
      gait velocity on an ascending slope, we hypothesized that higher impact transfer
      to the knee joints occurs in subjects with flatfeet due to the lack of a medial
      longitudinal arch and that the abductor halluces muscles, which provide dynamic
      stability to the medial longitudinal arches, do not activate well when they are
      needed in subjects with flatfeet. 

PMID- 24926131
TI  - Effects of tai chi on pain and muscle activity in young males with acute low back
      pain.
AB  - [Purpose] This study was to examine the effects of tai chi on low back pain in
      young males. [Subjects and Methods] Forty males in their 20s with low back pain
      were randomly assigned to two groups. Tai chi was applied to one group, and
      stretching was applied to the other group. The subjects conducted exercise for
      one hour, three times per week for four weeks. They performed warm-up exercises
      for 10 min at the beginning and end of the sessions and conducted the main
      exercise for 40 minutes. Wireless surface electromyography (sEMG) and a visual
      analogue scale (VAS) were employed to measure muscle activity and pain,
      respectively. [Results] There were significant differences between the two groups
      in pain and muscle activity. The tai chi group's VAS decreased from 3.1 to 2.1,
      and its muscle activity decreased from 21.5% maximum voluntary isomeric
      contraction (MVIC) to 16.4% MVIC. The stretching group's VAS decreased from 3.4
      to 2.8, and its muscle activity decreased from 24.1% MVIC to 22.1% MVIC.
      [Conclusion] Tai chi is more effective for low back pain in males in their 20s
      than stretching. Tai chi can be considered an effective method to reduce low back
      pain in males in their 20s. 

PMID- 24926132
TI  - Postural Stability and Subsequent Sports Injuries during Indoor Season of
      Athletes.
AB  - [Purpose] The aim of this study was to analyze stabilometry in athletes during an
      indoor season in order to determine whether injured athletes show different
      stabilometric values before injury than non-injured athletes in two different
      training periods (volume and pre-competition periods). [Subjects] The subjects
      were 51 athletes from Unicaja athletic club who trained regularly. [Methods] At
      the end of the preseason and volume periods, athletes were subjected to bipodal
      and monopodal stabilometry. In addition, all injuries happening in the periods
      after performing stabilometry (volume and pre-competition periods) were tracked.
      [Results] Variance analysis of bipodal stabilometric measurements taken at the
      end of the preseason period showed that athletes with higher values for the
      center-of-pressure spread variables suffered injuries during the volume period.
      The right-leg monopodal stabilometric measurements taken at the end of the volume
      period showed that athletes with higher values in the center-of-pressure position
      variables suffered injuries during the pre-competition period. [Conclusion]
      Athletes showing the worst values for center-of-pressure spread variables are
      more prone to sports injuries in the subsequent training period. In monopodal
      measurements, athletes with poorer mediolateral stability were more prone to
      injuries in the subsequent training period. 

PMID- 24926133
TI  - Correlation of shoulder and elbow injuries with muscle tightness, core stability,
      and balance by longitudinal measurements in junior high school baseball players.
AB  - [Purpose] The present study longitudinally investigated injury occurrences and
      the risk factors for muscle tightness, core stability, and dynamic standing
      balance among junior high school student baseball players. [Subjects] Thirty-nine
      male students, belonging to baseball clubs at 2 junior high schools, participated
      in this study. [Methods] Study measurements were obtained twice, once in the
      early stage of the baseball season (March) and once at the end of the season
      (July). All subjects underwent muscle tightness testing, the Star Excursion
      Balance Test (SEBT), and trunk endurance testing during each measurement session.
      [Results] Fifteen players experienced episodes of elbow or shoulder pain while
      throwing. Players in the pain group demonstrated a significant increase in the
      tightness of their shoulder internal rotators, axis-leg quadriceps, and axis-leg
      hamstrings. There was no clear evidence of differences of changes in core
      stability and dynamic standing balance between the groups. [Conclusion] The
      results of this study suggest that lower extremity muscle tightness early in a
      season and the subsequent decline in the flexibility of the axis-leg quadriceps
      and hamstrings during the season may be due to an increased upper extremity load
      while throwing, thus producing shoulder and elbow pain. 

PMID- 24926134
TI  - Factors increasing physical activity levels in diabetes mellitus: a survey of
      patients after an inpatient diabetes education program.
AB  - [Purpose] The aim of this study was to understand the factors involved in
      increasing physical activity levels in type 2 diabetes mellitus patients for
      improved glycemic control. [Subjects] The subjects were 101 type 2 diabetes
      mellitus patients who had completed an inpatient diabetes education program.
      [Methods] The survey evaluated physical activity levels on the basis of the
      International Physical Activity Questionnaire and a questionnaire listing
      physical and psychosocial factors. [Results] Four variables-participation or non
      participation in farm work, presence or absence of a job, stage of change in
      attitude toward exercise behavior, and social support-accounted for 34% of
      physical activity levels in these diabetes mellitus patients. The Spearman's rank
      correlation coefficient between physical activity level and HbA1c was -0.31.
      [Conclusion] Intervention in terms of practical use of living environments,
      promotion of exercise behavior, and social support may be effective in helping to
      improve glycemic control. 

PMID- 24926135
TI  - Effect of rotational axis position of wheelchair back support on shear force when
      reclining.
AB  - [Purpose] The purpose of this study was to investigate the influence of the
      rotational axis position of a reclining wheelchair's back support on fluctuations
      in the shear force applied to the buttocks while the back support is reclined.
      [Subjects] The subjects were 12 healthy adult men. [Methods] The shear force
      applied to the buttocks was measured using a force plate. This study used two
      different experimental conditions. The rotational axis of the back support was
      positioned at the joint between the seat and the back support for the rear-axis
      condition, and was moved 13 cm forward for the front-axis condition. [Results]
      With the back support fully reclined, the shear forces were 11.2 +/- 0.8%BW and
      14.1 +/- 2.5%BW under the rear-axis and front-axis conditions, respectively. When
      returned to an upright position, the shear forces were 17.1 +/- 3.1%BW and 13.8
      +/- 1.7%BW under the rear-axis and front-axis conditions, respectively.
      Significant differences appeared between the two experimental conditions (p <
      0.01). [Conclusion] These results suggest that the shear force value could be
      changed by altering the position of the back support's rotational axis during
      reclining. 

PMID- 24926136
TI  - The effects of aquatic exercise on pulmonary function in patients with spinal
      cord injury.
AB  - [Purpose] The purpose of this study was to determine the effects of aquatic
      exercise on pulmonary function of patients with spinal cord injury. [Subjects]
      The subjects were randomly allocated to an aqua group (n=10) and a land group
      (n=10). [Methods] Both groups trained for 60 minutes, 3 times a week for 8 weeks.
      Pulmonary function was assessed by measuring the forced vital capacity (FVC),
      forced expiratory flow rate (FER), force expiratory volume at one second (FEV1)
      and force expiratory volume at one second/forced vital capacity (FEV1/FVC).
      [Results] Following the intervention, the aqua group showed significant changes
      in FVC, FER, FEV1, and FEV1/FVC. The land group showed only significant
      differences FER. [Conclusion] The results of this study suggest the effects on
      the aqua group were significantly higher than those on the land group in patients
      with spinal cord injury. 

PMID- 24926137
TI  - Effects of therapeutic ultrasound on range of motion and stretch pain.
AB  - [Purpose] This study aimed to clarify the effects of therapeutic ultrasound on
      range of motion and stretch pain and the relationships between the effects.
      [Subjects] The subjects were 15 healthy males. [Methods] Subjects performed all
      three interventions: (1) ultrasound (US group), (2) without powered ultrasound
      (placebo group), and (3) rest (control group). Ultrasound was applied at 3 MHz
      with an intensity of 1.0 W/cm(2) and a 100% duty cycle for 10 minutes. The
      evaluation indices were active and passive range of motion (ROM), stretch pain
      (visual analog scale; VAS), and skin surface temperature (SST). The experimental
      protocol lasted a total of 40 minutes; this was comprised of 10 minutes before
      the intervention, 10 minutes during the intervention (US, placebo, and control),
      and 20 minutes after the intervention. [Results] ROM and SST were significantly
      higher in the US group than in the placebo and control groups for the 20 minutes
      after ultrasound, though there was no change in stretch pain. [Conclusion] The
      effects of ultrasound on ROM and SST were maintained for 20 minutes after the
      intervention. The SST increased with ultrasound and decreased afterwards.
      Additionally, the SST tended to return to baseline levels within 20 minutes after
      ultrasound exposure. Therefore, these effects were caused by a combination of
      thermal and mechanical effects of the ultrasound. 

PMID- 24926138
TI  - The Influence of Dual Pressure Biofeedback Units on Pelvic Rotation and Abdominal
      Muscle Activity during the Active Straight Leg Raise in Women with Chronic Lower
      Back Pain.
AB  - [Purpose] This study was performed to assess the influence of applying dual
      pressure biofeedback units (DPBUs) on the angle of pelvic rotation and abdominal
      muscle activity during the active straight leg raise (ASLR). [Subjects] Seventeen
      patients with low-back pain (LBP) participated in this study. [Methods] The
      subjects were asked to perform an active straight leg raise (ASLR) without a PBU,
      with a single PBU, and with DPBUs. The angles of pelvic rotation were measured
      using a three-dimensional motion-analysis system, and the muscle activity of the
      bilateral internal oblique abdominis (IO), external oblique abdominis (EO), and
      rectus abdominis (RA) was recorded using surface electromyography (EMG). One-way
      repeated-measures ANOVA was performed to determine the rotation angles and muscle
      activity under the three conditions. [Results] The EMG activity of the
      ipsilateral IO, contralateral EO, and bilateral RA was greater and pelvic
      rotation was lower with the DPBUs than with no PBU or a single PBU. [Conclusion]
      The results of this study suggest that applying DPBUs during ASLR is effective in
      decreasing unwanted pelvic rotation and increasing abdominal muscle activity in
      women with chronic low back pain. 

PMID- 24926139
TI  - Functionality in Women with Breast Cancer: The Use of International
      Classification of Functioning, Disability and Health (ICF) in Clinical Practice.
AB  - [Purpose] The aim of this study was to evaluate the functionality of women
      diagnosed with breast cancer according to the International Classification of
      Functioning, Disability and Health (ICF). [Subjects and Methods] This was a cross
      sectional study. We applied instruments consistent with the summary of ICF codes
      for breast cancer: quality of life questionnaire (WHOQOL), upper limb symptoms
      and function (DASH), social support, physical examination and functional medical
      record data. [Results] The study included 105 women who were 55 years old and
      subjected to surgical treatment within an average of 1.63 year previously. The
      'function' component considered in the WHOQOL, the DASH and physical examination.
      There were high prevalences of positive responses for most codes, and only b130,
      d430, d445, d640, d650, d920 and codes of environmental factors considered by the
      Social Support Questionnaire showed high prevalences of negative responses
      (47.6%, 61%, 43.8%, 63.8%, 56.2%, 52.4%, and 35.2%, respectively). [Conclusion]
      There was a lower prevalence of disability, with the exception of issues related
      to strenuous activity and load. Some findings showed conflicting results between
      different instruments that measure the same code, and studies that propose more
      accurate tools and are able to consider the ICF codes specific to this pathology
      are necessary. 

PMID- 24926140
TI  - The effects of inaccessible visual feedback used concurrently or terminally.
AB  - [Purpose] Concurrent feedback is more detrimental for long-term retention of
      motor skills because learners depend on accessible visual information provided in
      parallel with movements. However, visual information is not always accessible.
      Furthermore, the effects of concurrent feedback vary with aspects of the task
      being performed. We investigated the effects of inaccessible visual feedback used
      concurrently or terminally, focusing on aspects of movement. [Subjects and
      Methods] Fourteen subjects were quasi-randomly assigned to either a concurrent
      feedback group or a terminal feedback group. They practiced a task that involved
      right shoulder flexion with a specific acceleration. Learning achievements were
      assessed by measurement of errors in movement duration, peak timing, and
      strength. [Results] Regarding errors in movement duration, the concurrent
      feedback group was superior to the terminal feedback group during the midterm and
      final sessions. Regarding errors in peak timing, learning occurred in the
      concurrent feedback group, but not in the terminal feedback group because the
      improvement in performance during practice was inadequate. Regarding errors in
      peak strength, learning occurred in both groups. [Conclusion] Concurrent visual
      feedback that is used inaccessibly has learning effects that either equal or
      surpass those of terminal feedback that is used with inaccessible visual
      information for all parameters. 

PMID- 24926141
TI  - Kinetic Relationships between the Hip and Ankle Joints during Gait in Children
      with Cerebral Palsy: A Pilot Study.
AB  - [Purpose] The purpose of this study was to evaluate kinetic relationships between
      the ankle and hip joints during gait, in the late stance, in children with
      spastic cerebral palsy (CP). [Subjects] The subjects were 3 ambulant children
      with spastic hemiplegic CP (aged 10, 13, and 14: CP group) and 3 typically
      developing children with the same ages (control). [Methods] A three-dimensional
      gait analysis including force data was performed to compare the peak moment,
      power, and ankle/hip power ratio between the hemiplegic (uninvolved and
      hemiplegic) and the control groups. In the statistical analysis, mean values from
      5 gait cycles for each of 3 conditions (uninvolved, hemiplegic and control) were
      used. The three conditions were compared by performing a Kruskal-Wallis test and
      Steel-Dwass multiple comparisons. [Results] The peak moments of ankle plantar
      flexors in the 10-year-old case, were significantly lower on the uninvolved and
      hemiplegic sides compared with the control group, respectively. The peak flexion
      moments of the hip on the hemiplegic side were significantly higher compared with
      the control in the 14- and 13-year-old cases. The peak of ankle power generation
      (A2) in the 13- and 10-year-old cases were significantly lower on the uninvolved
      and hemiplegic sides, respectively, compared with the control. The peaks of hip
      flexor power generation (H3) in the 14- and 13-year-old cases were significantly
      higher on the uninvolved and hemiplegic sides, respectively. The A2/H3 ratios
      were significantly lower on the uninvolved and hemiplegic sides compared with the
      control, and the ratio for the hemiplegic side was lower than that for the
      uninvolved side. [Conclusion] This study shows that propulsion of walking is
      generated by hip, rather than the ankle, on both the hemiplegic and involved
      sides. 

PMID- 24926142
TI  - Motor Learning in the Community-dwelling Elderly during Nordic Backward Walking.
AB  - [PURPOSE] THE AIMS OF THIS STUDY WERE: 1) to confirm the motion learning process
      of Nordic backward walking (NBW) in older adult community-dwelling volunteers
      and, 2) to check the change in psychological condition resulting from NBW. This
      study examined whether the learning process and psychological condition become
      more efficient after repeated sessions of NBW. [Methods] The subjects were 19
      community-dwelling elderly individuals between the ages of 64 and 78 years.
      [Results] Significant differences in walking speed during NBW were only found
      between the first and second sessions and between the second and third sessions.
      The walking speed in the sixth session, measured one hour after the fifth
      session, was decreased in comparison with that in the fifth session. Significant
      differences in stride length during NBW were only found between the first and
      second sessions and between the second and third sessions. The stride length in
      the sixth session, measured one hour after the fifth session, was decreased in
      comparison with that in the fifth session. Significant differences in VAS score
      (sense of fear) after NBW were found for each session. VAS score for the sixth
      session, measured one hour after the fifth session, was decreased in comparison
      with that for the fifth session. [Conclusions] The findings in the present study
      suggest that NBW is indeed a novel task and that motor learning occurs as a
      result of practice, leading to a more efficient recruitment of motor units.

PMID- 24926143
TI  - Effect of isometric quadriceps exercise on muscle strength, pain, and function in
      patients with knee osteoarthritis: a randomized controlled study.
AB  - [Purpose] The aim of present study was to investigate the effects of isometric
      quadriceps exercise on muscle strength, pain, and function in knee
      osteoarthritis. [Subjects and Methods] Outpatients (N=42, 21 per group; age range
      40-65 years; 13 men and 29 women) with osteoarthritis of the knee participated in
      the study. The experimental group performed isometric exercises including
      isometric quadriceps, straight leg raising, and isometric hip adduction exercise
      5 days a week for 5 weeks, whereas the control group did not performed any
      exercise program. The outcome measures or dependent variables selected for this
      study were pain intensity, isometric quadriceps strength, and knee function.
      These variables were measured using the Numerical Rating Scale (NRS), strength
      gauge device, and reduced WOMAC index, respectively. All the measurements were
      taken at baseline (week 0) and at the end of the trial at week 5. [Results] In
      between-group comparisons, the maximum isometric quadriceps strength, reduction
      in pain intensity, and improvement in function in the isometric exercise group at
      the end of the 5th week were significantly greater than those of the control
      group (p<0.05). [Conclusion] The 5-week isometric quadriceps exercise program
      showed beneficial effects on quadriceps muscle strength, pain, and functional
      disability in patients with osteoarthritis of the knee. 

PMID- 24926145
TI  - Comparison of Cervical Range of Motion and Cervical FRR between Computer Users in
      Their Early and Late 20s in Korea.
AB  - [Purpose] This study compared the cervical range of motion and cervical FRR
      between computer users in their early and late 20s in Korea. [Subjects] Eleven
      male and 7 female computer users in their early 20s and 10 male and 6 female
      computer users in their late 20s participated in this study. [Methods] All
      cervical ROM measurements were taken with a Cervical Range of Motion Instrument.
      Electromyographic (EMG) data were obtained for analyzing the FR ratio. [Results]
      Cervical extension, right and left lateral flexion, and right and left rotation
      in the late 20s computer users were significantly lower compared with the
      cervical motions in the early 20s computer users. The cervical FRR in the late
      20s computer users was significantly lower compared with the cervical FRR in the
      early 20s computer users. [Conclusion] This study was conducted to be prepared
      that the possibility for young computer generations in Korea could easily develop
      chronic neck pain. 

PMID- 24926144
TI  - Electromyographic Activities of Trunk Muscles Due to Different Exercise
      Intensities during Pulley-based Shoulder Exercises on an Unstable Surface.
AB  - [Purpose] This study examined the relationship between core stability and
      exercise intensity during a pulley-based shoulder exercise (PBSE) on an unstable
      support surface. [Subjects] Twenty healthy college students enrolled in this
      study. [Methods] Surface EMG was carried out in twenty healthy adult men. The
      electromyographic activities of the rectus abdominis (RA), erector spinae (ES),
      exercises with 14 kg or 26 kg of resistance and external oblique (EO) muscles
      during pulley-based shoulder on an unstable support surface (USS) were compared.
      [Results] The EMG signals of the RA, ES, and EO did not increase with increasing
      exercise resistance. [Conclusion] Increasing the exercise intensity to increase
      the core stability during PBSE on a USS may be ineffective. 

PMID- 24926146
TI  - A 3-month Follow-up Study of the Long-term Effects of Direct Stretching of the
      Tensor Fasciae Latae Muscle in Patients with Acute Lumbago Using a Single-case
      Design.
AB  - [Purpose] A 3-month follow-up study was conducted on a patient diagnosed with
      acute nonspecfic lumbago. Direct stretching (DS) of the tensor fasciae latae
      muscle (TFLM) was performed, and an immediate effect was confirmed. [Subjects]
      The case subject was a 60-year-old woman diagnosed with acute nonspecific
      lumbago. [Methods] We used a single-case study design and an AB-type study
      structure, in which the leg was placed in positions that relieved the back pain
      in period A and DS of the TFLM was performed in period B. The evaluation indices
      were the visual analog scale (VAS), finger-to-floor distance (FFD), and posterior
      lumbar flexibility (PLF), which were analyzed using the binomial test. [Results]
      The VAS, FFD, and PLF in period B showed significant improvement when compared
      with period A. Additionally, complaints of lower back pain ceased after 2 weeks,
      and the results of the follow-up study showed no recurrence of back pain during
      the 3 months. [Conclusion] The results of this study suggest that DS of the TFLM
      has an immediate effect on acute nonspecific lumbago in addition to long-term
      pain relief effects. 

PMID- 24926147
TI  - Effects of pelvic adjustment on female university students' gait variables.
AB  - [Purpose] The purpose of this study was to examine the effects of pelvic
      adjustment using Gonstead techniques on posture in female university students.
      [Subjects] In this study, 30 female university students were selected and divided
      into a pelvic adjustment group of 15 subjects as an experimental group and a
      stretching group of 15 subjects as a control group. [Methods] Step length
      difference (SLD), stance phase difference (STPD), swing phase difference (SWPD),
      single support difference (SSD), and step time difference (STD) were evaluated in
      the subjects using an OptoGait. [Results] Whereas the adjustment group showed
      statistically significant differences in SLD, STPD, SWPD, SSD, and STD, the
      stretching group did not show any statistically significant differences in any of
      the items. [Conclusion] Pelvic adjustment can be applied using Gonstead
      techniques as a method of reducing differences in normal gait variables between
      the left and right sides in adults. 

PMID- 24926148
TI  - The effect of ankle taping and balance exercises on postural stability indices in
      healthy women.
AB  - [Purpose] The purpose of this study was to compare the effect of ankle taping and
      balance exercises on postural stability indices in healthy women. [Subjects and
      Methods] Thirty healthy female students were randomly assigned into two equal
      groups: ankle taping and balance exercise. The balance exercise group performed
      balance exercises for 6 weeks, with 3 sessions per week and each session lasting
      40 minutes. Ankle joint taping was performed for 6 weeks and was renewed three
      times a week. Before and after the interventions, overall, anteroposterior, and
      mediolateral stability indices were measured with a Biodex Balance System in
      bilateral and unilateral stance positions with the eyes open and closed.
      [Results] In the taping group during bilateral standing with the eyes closed, the
      overall stability index changed from 6+/-1.4 to 4.8+/-1.3, anteroposterior
      stability index changed from 4.2+/-1.27 to 3.4+/-0.97, and mediolateral stability
      index changed from 3.2+/-0.75 to 2.7+/- 0.7. In the balance exercise group during
      bilateral standing with the eyes closed, the overall stability index changed from
      5.7+/-1.69 to 4.5+/-1.94, anteroposterior stability index changed from 4.1+/-1.61
      to 3+/-1.21, and mediolateral stability index changed from 3.5+/-1.4 to 2.2+/-
      1.3. No significant difference was seen between the two groups regarding any
      study variables. [Conclusion] The results showed that compared with the taping
      technique, balance training increases postural stability in the majority of the
      studied balance situations. 

PMID- 24926149
TI  - Clinical Reasoning of Physical Therapists regarding In-hospital Walking
      Independence of Patients with Hemiplegia.
AB  - [Purpose] Physical therapists must often determine whether hemiparetic patients
      can walk independently. However, there are no criteria, so decisions are often
      left to individual physical therapists. The purpose of this study was to explore
      how physical therapists determine whether a patient with hemiplegia can walk
      independently in a ward. [Methods] The subjects were 15 physical therapists with
      experience of stroke patients' rehabilitation. We interviewed them using semi
      structured interviews related to the criteria of the states of walking in the
      ward of hemiparetic patients. The interviews were transcribed in full, and the
      texts were analyzed by coding and grouping. [Results] From the results of the
      interviews, PTs determined patients' independence of walking in hospital by
      observation of behavior during walking or treatment. The majority of PTs focused
      on the patients' state during walking, higher brain function, and their ability
      to balance. In addition, they often asked ward staff about patients' daily life,
      and self-determination. [Conclusions] We identified the items examined by
      physical therapists when determining the in-hospital walking independence of
      stroke patients. Further investigation is required to examine which of these
      items are truly necessary. 

PMID- 24926150
TI  - Optimal and Maximal Loads during Hip Adduction Exercise by Asymptomatic People.
AB  - [Purpose] The purpose of this study was to provide data for decision making
      regarding the optimal and maximal hip adduction loads for clinical and fitness
      purposes, respectively. [Subjects] Forty-eight (24 males, 24 females)
      asymptomatic adults participated in this study. [Methods] Subjects performed
      optimal and maximal hip adduction loads. Regarding the gender, body weight and
      height variables, a stepwise multiple regression analysis was used to identify
      the most informative variables for predicting the optimal and maximal loads
      during the hip adduction exercise. [Results] The regression model for optimal hip
      adduction load (kg) was: 34.3 + 0.4 * weight - 0.27 * height (r(2)= 0.77); and
      the regression model for maximal hip adduction load (kg) was: 39.5 + 0.5 * weight
      - 0.3 * height (r(2)= 0.75). [Conclusion] These models can aid in deciding the
      optimal and maximal hip adduction loads for clinical and fitness purposes,
      respectively. Thus, the optimal hip adduction load model can be used to
      strengthen the hip adductor muscles or enhance core stability in clinical
      settings. 

PMID- 24926151
TI  - A Cross-sectional Study of Resting Cardio-respiratory and Metabolic Changes in
      Pregnant Women.
AB  - [Purpose] We examined cardiorespiratory and metabolic changes across the 1st
      (G1), 2nd (G2) and 3rd (G3) trimesters in pregnant women. [Subjects and Methods]
      Forty-two healthy, active, non-smoking, pregnant women participated in this
      study. They were divided into G1, G2 and G3 groups depending on their mean
      gestational ages at the time of testing which were 10.5 +/-2.9, 19.2 +/-3.4, and
      33.3 +/-2.4 weeks of gestation, respectively. Cardio-respiratory and metabolic
      variables, VO2 (oxygen consumption), VCO2 (carbon dioxide production), and VE
      (minute ventilation), were measured using indirect calorimetry (IC, gas analyser)
      to estimate ventilatory equivalents of oxygen (VE/VO2) and carbon dioxide
      (VE/VCO2), RER (respiratory exchange ratio) and REE (resting energy expenditure).
      [Results] Women in the late pregnancy period had higher resting VCO2 and RER,
      whereas the VE/VCO2 ratio was significantly lower than in G1 and in G2. Even
      though the values of VO2 and REE increased throughout the course of pregnancy, no
      significant differences were found. [Conclusion] In pregnant women, resting
      cardiorespiratory and metabolic variables continuously changed throughout the 3
      trimesters. Changes in VE/VCO2 and RER indicate shifting metabolic energy
      substrates. In addition, changes in cardiorespiratory variables, in parallel with
      gas exchange, indicate a better gas exchange process. 

PMID- 24926152
TI  - Comparison of the Symmetry of Right and Left Lateral Cervical Flexion and
      Rotation and the Cervical FRR in Young Computer Workers.
AB  - [Purpose] This study compared the symmetry of right and left lateral cervical
      flexion and rotation, and the cervical flexion-relaxation ratio (FRR) in young
      computer workers in Korea. [Subjects and Methods] Twenty computer workers (14
      males and 6 females) participated in this study. We measured their right and left
      lateral cervical flexion, rotation, and FRR. [Results] Right and left lateral
      flexion and right and left rotation showed no significant differences between the
      sides. The left cervical FRR was significantly lower than the right cervical FRR.
      [Conclusion] The cervical FRR, expressed as a numerical value, is a more
      sensitive marker for measuring neuromuscular changes associated with mild
      asymmetry than CROM. 

PMID- 24926153
TI  - Changes in neck muscle thickness due to differences in intermittent cervical
      traction force measured by ultrasonography.
AB  - [Purpose] Many patients receive intermittent cervical traction in a daily
      treatment setting. However, unified settings for traction force, duration, and
      direction have yet to be determined. Therefore, an objective index is required to
      determine changes in traction conditions or to indicate its effectiveness.
      [Subjects] Fifteen healthy males volunteers participated in this study. [Methods]
      The thickness of the trapezius and splenius capitis muscles before and during
      traction were measured using ultrasonography at three traction forces: 5, 8 and
      11 kg. [Results] Significant differences in muscle thickness were observed at 11
      kg in the trapezius, and at 8 kg and 11 kg in the splenius capitis muscles. The
      muscle thickness ratio of the trapezius muscle showed a significant difference
      between 11 kg and 5 and 8 kg, and between 5 kg and 8 and 11 kg, as well as
      between 8 kg and 11 kg for the splenius capitis muscles. [Conclusion] Differences
      in muscle direction between the trapezius and splenius capitis muscles may
      account for the contrasting results obtained at the 8 kg traction force. This
      finding suggests that cervical traction must be performed considering the effects
      on different neck regions. 

PMID- 24926154
TI  - A Review of Signal Transduction of Endothelin-1 and Mitogen-activated Protein
      Kinase-related Pain for Nanophysiotherapy.
AB  - [Purpose] An understanding of pain is very important in the study of
      nanophysiotherapy. In this review, we summarize the mechanisms of endothelin-1
      (ET-1)- and mitogen-activated protein kinase (MAPK)-related pain, and suggest
      their applications in pain physiotherapy. [Method] This review focuses on the
      signal transduction of pain and its mechanisms. [Results] Our reviews show that
      mechanisms of ET-1- and MAPK-related pain exist. [Conclusions] In this review
      article, we carefully discuss the signal transduction in ET-1- and MAPK-related
      pain with reference to pain nanophysiotherapy from the perspective of
      nanoparticle-associated signal transduction. 

PMID- 24926155
TI  - Non-surgical Intervention of Knee Flexion Contracture in Children with Spina
      Bifida: Case Report.
AB  - [Purpose] The purpose of this case report is to describe for the first time, the
      use of serial casting in the management of knee joint flexion contracture for a
      young child with spina bifida. [Case Description] The child was 6 years old, and
      had L3-L4 spina bifida level lesion with quadriceps muscle strength grade 3 +.
      The child had previously received weekly physiotherapy including stretching for
      knee flexion contracture on both lower limbs, but without improvement. [Results]
      The knee flexion contracture, which was not corrected with passive stretching,
      improved with casting from -40 degrees  knee extension to -5 degrees  knee
      extension as measured by a standard goniometer over a period of 4 weeks. Careful
      measures were taken to ensure skin integrity. At follow up after one-year, the
      child could ambulate independently with the help of walking aids. [Conclusion]
      The outcome indicates that using serial casting and follow-up with the use of
      bracing may be useful for enhancing the walking ability of a young child with
      spina bifida with knee flexion contractures. Further investigations of serial
      casting as well as investigation of serial casting with other interventions are
      warranted. 

PMID- 24926156
TI  - The use of propensity scores to assess the generalizability of results from
      randomized trials.
AB  - Randomized trials remain the most accepted design for estimating the effects of
      interventions, but they do not necessarily answer a question of primary interest:
      Will the program be effective in a target population in which it may be
      implemented? In other words, are the results generalizable? There has been very
      little statistical research on how to assess the generalizability, or "external
      validity," of randomized trials. We propose the use of propensity-score-based
      metrics to quantify the similarity of the participants in a randomized trial and
      a target population. In this setting the propensity score model predicts
      participation in the randomized trial, given a set of covariates. The resulting
      propensity scores are used first to quantify the difference between the trial
      participants and the target population, and then to match, subclassify, or weight
      the control group outcomes to the population, assessing how well the propensity
      score-adjusted outcomes track the outcomes actually observed in the population.
      These metrics can serve as a first step in assessing the generalizability of
      results from randomized trials to target populations. This paper lays out these
      ideas, discusses the assumptions underlying the approach, and illustrates the
      metrics using data on the evaluation of a schoolwide prevention program called
      Positive Behavioral Interventions and Supports.

PMID- 24926157
TI  - An analysis of functional shoulder movements during task performance using
      Dartfish movement analysis software.
AB  - PURPOSE: Video-based movement analysis software (Dartfish) has potential for
      clinical applications for understanding shoulder motion if functional measures
      can be reliably obtained. The primary purpose of this study was to describe the
      functional range of motion (ROM) of the shoulder used to perform a subset of
      functional tasks. A second purpose was to assess the reliability of functional
      ROM measurements obtained by different raters using Dartfish software. MATERIALS
      AND METHODS: Ten healthy participants, mean age 29 +/- 5 years, were videotaped
      while performing five tasks selected from the Disabilities of the Arm, Shoulder
      and Hand (DASH). Video cameras and markers were used to obtain video images
      suitable for analysis in Dartfish software. Three repetitions of each task were
      performed. Shoulder movements from all three repetitions were analyzed using
      Dartfish software. The tracking tool of the Dartfish software was used to obtain
      shoulder joint angles and arcs of motion. Test-retest and inter-rater reliability
      of the measurements were evaluated using intraclass correlation coefficients
      (ICC). RESULTS: Maximum (coronal plane) abduction (118 degrees  +/- 16 degrees )
      and (sagittal plane) flexion (111 degrees  +/- 15 degrees ) was observed during
      'washing one's hair;' maximum extension (-68 degrees  +/- 9 degrees ) was
      identified during 'washing one's own back.' Minimum shoulder ROM was observed
      during 'opening a tight jar' (33 degrees  +/- 13 degrees  abduction and 13
      degrees  +/- 19 degrees  flexion). Test-retest reliability (ICC = 0.45 to 0.94)
      suggests high inter-individual task variability, and inter-rater reliability (ICC
      = 0.68 to 1.00) showed moderate to excellent agreement. CONCLUSION: KEY FINDINGS
      INCLUDE: 1) functional shoulder ROM identified in this study compared to similar
      studies; 2) healthy individuals require less than full ROM when performing five
      common ADL tasks 3) high participant variability was observed during performance
      of the five ADL tasks; and 4) Dartfish software provides a clinically relevant
      tool to analyze shoulder function.

PMID- 24926158
TI  - Oxford shoulder score in a normal population.
AB  - BACKGROUND: The function of the asymptomatic normal shoulder may differ according
      to gender and could also deteriorate with age. This may result in a disparity in
      the normal Oxford shoulder score (OSS) according to these variables. If a
      difference were to exist an adjusted OSS, for age and gender, could be calculated
      from the raw score using the expected normal score. AIM: The aim of this study
      was to define a normal OSS in an asymptomatic population according to age and
      gender. MATERIALS AND METHODS: During the study period 202 patients aged from 20
      years to 99 years with subjectively asymptomatic shoulders completed an OSS.
      These patients presented to the study center during a 1 week period for
      management of disorders out with their shoulder girdle. Patients with a known
      prior shoulder pathology, injury, or polyarthropathy were excluded. RESULTS: The
      mean OSS varied according age and gender. There was a significant correlation
      between age and the OSS, with an increasing score (worse) being associated with
      older age (r = 0.62, P < 0.0001). The mean OSS for females was 18.8 (12-42, SD
      5.4) and for males was 16.3 (12-30, SD 4.5), this difference was significant (P =
      0.0001). We propose that a normalized OSS could be calculated as a percentage by
      the using the expected normal for that patient's age and gender as demonstrated
      in this study ((raw score/normal score) * 100). CONCLUSION: Our study provides
      normal data for an urban population presenting to orthopedic services and allows
      for a relative OSS to be calculated from the raw score.

PMID- 24926159
TI  - Single-row, double-row, and transosseous equivalent techniques for isolated
      supraspinatus tendon tears with minimal atrophy: A retrospective comparative
      outcome and radiographic analysis at minimum 2-year followup.
AB  - PURPOSE: The purpose of this study was to measure and compare the subjective,
      objective, and radiographic healing outcomes of single-row (SR), double-row (DR),
      and transosseous equivalent (TOE) suture techniques for arthroscopic rotator cuff
      repair. MATERIALS AND METHODS: A retrospective comparative analysis of
      arthroscopic rotator cuff repairs by one surgeon from 2004 to 2010 at minimum 2
      year followup was performed. Cohorts were matched for age, sex, and tear size.
      Subjective outcome variables included ASES, Constant, SST, UCLA, and SF-12
      scores. Objective outcome variables included strength, active range of motion
      (ROM). Radiographic healing was assessed by magnetic resonance imaging (MRI).
      Statistical analysis was performed using analysis of variance (ANOVA), Mann -
      Whitney and Kruskal - Wallis tests with significance, and the Fisher exact
      probability test <0.05. RESULTS: Sixty-three patients completed the study
      requirements (20 SR, 21 DR, 22 TOE). There was a clinically and statistically
      significant improvement in outcomes with all repair techniques (ASES mean
      improvement P = <0.0001). The mean final ASES scores were: SR 83; (SD 21.4); DR
      87 (SD 18.2); TOE 87 (SD 13.2); (P = 0.73). There was a statistically significant
      improvement in strength for each repair technique (P < 0.001). There was no
      significant difference between techniques across all secondary outcome
      assessments: ASES improvement, Constant, SST, UCLA, SF-12, ROM, Strength, and MRI
      re-tear rates. There was a decrease in re-tear rates from single row (22%) to
      double-row (18%) to transosseous equivalent (11%); however, this difference was
      not statistically significant (P = 0.6). CONCLUSIONS: Compared to preoperatively,
      arthroscopic rotator cuff repair, using SR, DR, or TOE techniques, yielded a
      clinically and statistically significant improvement in subjective and objective
      outcomes at a minimum 2-year follow-up. LEVEL OF EVIDENCE: Therapeutic level 3.

PMID- 24926160
TI  - Bone properties of the humeral head and resistance to screw cutout.
AB  - Surgical treatment of fractures involving the proximal humeral head is hampered
      by complications. Screw cutout is the major pitfall seen in connection with rigid
      plating. We have exploited a bony explanation for this phenomenon. MATERIALS AND
      METHODS: We examined the convex surface of the humeral head looking at the
      density and the topographical strength of the subchondral bone using mechanical
      testing of bone cylinders harvested from the humeral head. We also studied the
      osseous architecture of the subchondral bone and thickness of the boneplate of
      the humeral head using a 3-dimensional serial sectioning technique. RESULTS: The
      bone strength and bone density correlated well and revealed large regional
      variations across the humeral head. Bone strength and stiffness of the trabecular
      bone came to a maximum in the most medial anterior and central parts of the
      humeral head, where strong textural anisotropy was also found. We found in
      particular a lower bone strength and density in the posterior and inferior
      regions of the humeral head. A rapid decline in bone strength within a few mm
      below a relatively thin subchondral plate was also reported. CLINICAL RELEVANCE:
      We have in this paper explored some of the most important factors connected with
      screw stability at the cancellous bone level. We discovered large variations in
      bone density and bone strength across the joint surface rendering certain areas
      of the humeral head less suitable for screw placement. The use of rigid plate
      constructs with divergent screw directions will predictably place screws in areas
      of the humeral head comprising low density and low strength cancellous bone. New
      concepts of plates and plating techniques for the surgical treatment of complex
      fractures of the proximal humerus should take bone distribution, strength, and
      architecture into account.

PMID- 24926161
TI  - Combination of a floating clavicle and a posterior shoulder dislocation: An
      "Unhappy Triad" of the shoulder girdle.
AB  - We present a case of a 31-year-old man who suffered from a floating clavicle in
      combination with a reverse Hill-Sachs lesion of his right shoulder girdle after a
      bicycle accident. Operative treatment was performed using minimal-invasive and
      arthroscopically assisted techniques. We strongly recommend an early CT scan with
      later 3-dimensional reconstruction to detect and fully understand these complex
      injuries. 

PMID- 24926162
TI  - Recurrent Fusobacterium pyogenic myositis of the rotator cuff A case report of
      recurrent Fusobacterium pyogenic myositis of the rotator cuff.
AB  - Pyogenic myositis is uncommon. It normally affects the large muscle groups in the
      lower limb or trunk and the most common causative organism is Staphylococcus
      aureus. We present a case of an immunocompetent man who, unusually, had a
      recurring form of the disease in subscapularis and teres minor. The causative
      organism was also highly unusual (Fusobacterium). 

PMID- 24926163
TI  - Distal humerus shear-fractures: "Built-on" surgical technique.
AB  - When treating a distal humeral shear fracture, comminution of the lateral column
      may preclude the reconstruction of the lateral articular fragments. In this
      article a new strategy for the management lateral column comminuted shear
      fractures (LCCSF) is presented, called the "built-on" surgical technique. Three
      goals are obtained by this technique: (1) Restoration of the lateral column bone
      stock; (2) Provision of a solid scaffold for the repair of the lateral ulnar
      collateral ligament (LUCL); and (3) Provision of a sable platform for the
      reconstruction and fixation of the articular fragments. We will obtain these
      goals through the following surgical steps: 1/ Reconstruction of the lateral
      trochlea. 2/ Reconstruction of the lateral column 3/ Fixation of the Capitellum
      4/ Reconstruction of the LUCL. 

PMID- 24926164
TI  - State of the globe: hepatitis a virus - return of a water devil.

PMID- 24926165
TI  - Investigating a community-wide outbreak of hepatitis a in India.
AB  - BACKGROUND: There was an outbreak of acute hepatitis in Mylapore village, Kollam
      district, Kerala, southern India during February to June 2013. An outbreak
      investigation was initiated with the objective of describing the epidemiological
      features of the hepatitis outbreak. MATERIALS AND METHODS: House-to-house visits
      were undertaken to identify symptomatic cases. The outbreak was described in
      terms of person, place and time. Hypothesis was generated based on findings from
      descriptive study, laboratory investigation of water samples, and environmental
      observations. A case-control study was designed to test the hypothesis. Chi
      square test, univariate analysis, and logistic regression to identify the risk
      factors associated with hepatitis A infection were done. RESULTS: Line list
      generated consisted of 45 cases. Attack rate was the highest among the age group
      15-24 years (4.6%) followed by 5-14 years (3.1%). The geographical distribution
      of the cases suggested a clustering around the water supply through the pipeline
      and epidemic curve showed a sharp rise in cases suggestive of a common source
      outbreak. Water samples collected form pipeline showed evidence of fecal
      contamination and absence of residual chlorine. In the case-control study, having
      consumed water from the pipeline (odds ratio: 9.01 [95% confidence interval: 2.16
      37.61]) was associated with the hepatitis A cases. CONCLUSION: The time frame of
      disease occurrence, environmental observations, anecdotal evidences, laboratory
      results and results of the analytical study indicated the possibility of
      occurrence of hepatitis A outbreak as a result of pipe water contamination
      supplied from a bore well. The study warrants establishment of an efficient water
      quality surveillance system.

PMID- 24926167
TI  - Acute pneumococcal myelitis in an adult patient.
AB  - Pneumococcal meningitis represents the most severe community-acquired bacterial
      meningitis. The disease is frequently associated with various complications. We
      present a case of pneumococcal meningitis in an immunocompetent adult patient
      treated with hypothermia. The disease course was complicated with severe myelitis
      and consequent paraplegia which is an extremely rare complication of pneumococcal
      disease. 

PMID- 24926166
TI  - Hepatic and biliary ascariasis.
AB  - Ascariasis mainly contributes to the global helminthic burden by infesting a
      large number of children in the tropical countries. Hepato-biliary ascariasis
      (HBA) is becoming a common entity now than in the past owing to the frequent
      usage of ultrasonograms and endoscopic diagnostic procedures in the clinical
      practice. There are a variety of manifestations in HBA and diagnosis depends on a
      high index of suspicion in endemic areas coupled with subsequent confirmation by
      sonographic or endoscopic demonstration of the worm. Most of them present with
      acute abdomen and jaundice. Oriental or recurrent pyogenic cholangiopathy is
      possibly the result of HBA, commonly encountered in South-East Asian countries.
      Conservative treatment with anthelminthic agents is used in the majority. Failure
      to respond to medical therapy usually indicates the need for endoscopic or
      surgical interventions. Overall, mortality is low and prognosis is good, but many
      epidemiological and immunological aspects of Ascaris infection are unclear,
      meaning our understanding the disease and infection still remains incomplete.
      Therefore, it is difficult to definitely put down a fixed modality of treatment
      for HBA. This underscores the need for further studies as ascariasis has the
      potential to adversely affect the national socio-economy by compromising the
      health of children and adults alike with its sheer number. 

PMID- 24926168
TI  - Acute pancreatitis complicating severe dengue.
AB  - Dengue is an arthropod borne viral infection endemic in tropical and subtropical
      continent. Severe dengue is life threatening. Various atypical presentations of
      dengue have been documented. But we present a rare and fatal complication of
      severe dengue in form of acute pancreatitis. A 27-year-old male had presented
      with severe dengue in decompensated shock and with pain in abdomen due to
      pancreatitis. The pathogenesis of acute pancreatitis in dengue is not clearly
      understood, but various mechanisms are postulated. The awareness and timely
      recognition of this complication is very important for proper management. 

PMID- 24926169
TI  - Acute arthritis in crimean-congo hemorrhagic Fever.
AB  - Crimean-Congo hemorrhagic fever is a severe viral disease caused by a Nairovirus.
      An atypical manifestation in the form of acute arthritis was found in a confirmed
      Crimean-Congo hemorrhagic fever virus Kosova-Hoti strain positive patient. Acute
      arthritis in Crimean-Congo hemorrhagic fever (CCHF) may be as a result of immune
      mechanisms or the bleeding disorder underlying CCHF. 

PMID- 24926170
TI  - Intravenous immunoglobulin in the treatment of severe clostridium difficile
      colitis.
AB  - Intravenous immunoglobulin (IVIG) has been utilized in patients with recurrent
      and refractory Clostridium difficile colitis. It is increasingly being used in
      patients with initial clinical presentation of severe colitis. Herein, we report
      a case of severe C. Difficile colitis successfully treated with IVIG with a
      review of the medical literature to identify the optimal timing and clinical
      characteristics for this treatment strategy. 

PMID- 24926171
TI  - Splenic infarct due to scrub typhus.
AB  - Scrub typhus is a mite borne infectious disease that has the potential to involve
      multiple organs and can be fatal. Involvement of the abdomen in the form of
      hepatitis, gastric ulcerations and pancreatitis are well-documented, the
      pathology being disseminated vasculitis. However involvement of the spleen in
      scrub typhus is extremely rare and is reported only in a few autopsy studies. We
      report the case of a 50-year-old lady who presented with fever and left upper
      quadrant abdominal pain due to a splenic infarct due to scrub typhus. 

PMID- 24926172
TI  - Tuberculous optochiasmatic arachnoiditis.

PMID- 24926173
TI  - Antimicrobial Susceptibility Pattern of Burkholderia cepacia Isolates from
      Patients with Malignancy.

PMID- 24926174
TI  - Primary Multi Drug Resistant Extra-pulmonary Tuberculosis Presenting as Cervical
      Lymphadenitis.

PMID- 24926175
TI  - Energy Transfer of CdSe/ZnS Nanocrystals Encapsulated with Rhodamine-Dye
      Functionalized Poly(acrylic acid).
AB  - Energy transfer between a CdSe/ZnS nanocrystal (NC) donor and a rhodamine
      isothiocyanate (RITC) acceptor has been achieved via a functionalized
      poly(acrylic acid) (PAA) encapsulating layer over the surface of the NC. The
      modification of PAA with both N-octylamine (OA) and 5-amino-1-pentanol (AP), [PAA
      OA-AP], allows for the simultaneous water-solubilization and functionalization of
      the NCs, underscoring the ease of synthesizing NC-acceptor conjugates with this
      strategy. Photophysical studies of the NC-RITC constructs showed that energy
      transfer is efficient, with kFRET approaching 108 s-1. The ease of the covalent
      conjugation of molecules to NCs with PAA-OA-AP coating, together with efficient
      energy transfer, makes the NCs encapsulated with PAA-OA-AP attractive candidates
      for sensing applications.

PMID- 24926176
TI  - New method for fixation point of tibialis posterior tendon transfer.
AB  - BACKGROUND: The transfer of the tibialis posterior tendon to the dorsum of foot
      can restore the function of theparalyzed dorsiflexor muscles of the foot and
      ankle. In order to reduce the wound complication in the insertionsite of tendon
      to bone by a plantar knop we used a new method of fixation by an absorbable screw
      inserted dorsally. METHODS: we performed this operation on 15 patients in a 3
      years period. All patients had drop foot deformitydue to irreversible lesions of
      the peroneal nerve. The inclusion criteria was the peroneal nerve palsy that
      wasnot improved after 18 months even by using nerve releasing or nerve repairing.
      All patients were evaluatedafter 6 months for ankle function and wound
      complications. RESULT: Of 15 patients one was excluded from study. At 6 month ten
      patients got excellent score (66%) and 4good score (26%) further ankle function.
      There was no wound complication at insertion site. CONCLUSION: This simple
      modification for insertion site fixation had good result in restoring ankle
      functionwhiles eliminated the possibility of plantar pressure sores caused by
      fixation knop.

PMID- 24926177
TI  - Trend of smoking among students of Tehran University of Medical Sciences: results
      from four consecutive surveys from 2006 to 2009.
AB  - BACKGROUND: Smoking within students community of the medical sciences can
      negatively impact the attitudesof the society in future. The objectives of this
      study were to assess the prevalence and trends of smoking amongstudents of Tehran
      University of Medical Sciences. METHOD: This study was conducted in four
      consecutive years from 2006 to 2009. The study sample was takenfrom the first- to
      fourth-year, undergraduate and graduate (doctorate) students of Tehran University
      of MedicalSciences. Census was applied for sampling. Structured questionnaires
      were distributed to students of each class.The study was anonymous and self
      administered. RESULTS: From 2006 to 2009, a total of 1568 to 1761 students
      participated in the study each year. Over thestudy period, i.e. 2006-2009, the
      prevalence of cigarette smoking was decreased (the overall prevalence was12.5% in
      2006, 12.9% in 2007, 10.8% in 2008, and 10.5% in 2009). The corresponding values
      for the onemonth prevalence were 8.2%, 7.8%, 6.1%, and 5.8%, while those for the
      prevalence of daily smoking were3.4%, 4.0%, 2.9%, and 1.8%, respectively. The
      decreasing trend was particularly more significant for femalestudents.
      CONCLUSION: The findings suggest that the prevalence of smoking among students of
      Tehran University ofMedical Sciences was in the lower end of the spectrum, in
      comparison to other universities in Iran and othercountries. Additionally,
      similar to the pattern observed in the developed world, this trend was
      decreasing, particularlyamong girls. Implementing preventive measures for
      accelerating the decreasing trend, as well as continuousmonitoring is
      recommended.

PMID- 24926178
TI  - Trend of diseases among Iranian pilgrims during five consecutive years based on a
      Syndromic Surveillance System in Hajj.
AB  - BACKGROUND: Every year more than 2 million people depart from Iran to Saudi
      Arabia for Hajj ritual whichcan be faced with some different diseases. There are
      not much information about frequencies and trend of diseasesin Hajj. The main
      objective of this study was to determine the trend of prevalent diseases during
      five consecutiveHajj rituals among Iranian pilgrims. METHODS: We established a
      specific surveillance system for all Iranian pilgrims who had participated in
      Hajjfrom 2004 to 2008. We monitored the pilgrims' health status before departure,
      through their journey. The understudieddiseases were 19 selected types of
      diseases in the Hajj. The occurrences of diseases were recorded on aresearchers
      made questionnaire. We used chi-square test for analysis with the alpha lower
      than 5% to reject thenull hypothesis. RESULTS: During 5 consecutive periods, a
      total of 254,823 of Iranian pilgrims were monitored for more commondiseases with
      this system. The most prevalent diseases were as follows: at least one type of
      respiratory involvement(71.26%), common cold like syndrome (47.15%), and
      musculoskeletal disorders (18.67%), The frequencyof respiratory involvement was
      lower in 2006 than other years (p <0.001).There were statistically
      significantdifferences between the numbers of hospitalization and patients who
      were referred back to Iran with theyear of Hajj (p <0.001). CONCLUSION: Health
      managers should be informed about trend and frequency of more prevalent diseases
      inHajj. Easy access to health information via such surveillance system can be
      possible.

PMID- 24926179
TI  - Sellar reconstruction algorithm in endoscopic transsphenoidal pituitary surgery:
      experience with 240 cases.
AB  - BACKGROUND: Proposing a strategy for sellar reconstruction in endoscopic
      transsphenoidal transsellar approachfor pituitary adenoma. METHODS: 240 patients
      with pituitary adenoma underwent pure endoscopic endonasal transsphenoidal
      surgery.Intra-operative CSF leaks were classified as grade 0, no observable leak;
      grade 1, CSF dripping through anarachnoid membrane defect of less than 1 mm; and
      grade 2, CSF flowing through an arachnoid defect of morethan 1 mm. Sellar
      reconstruction was performed according to our staging system; in stage I, the
      defect was coveredwith oxidized cellulose and sphenoid sinus filled up with
      Gelfoam. In stage II, a layer of fat was appliedon the defect and fascia lata
      placed epidurally. In stage III, one or two layers of fascia were used with
      addingsurgical glue and/or lumbar drainage. Mucosa of sphenoid sinuses was kept
      intact as much as possible and approximatedat the end of procedure. RESULT: intra
      operative CSF leaks grade 0, 1 and 2 resulted in 133(55.4%), 78 (32.5%) and
      29(12.1%) patients,respectively. Stage I of reconstruction was used in 126
      patients (52.5%) with no intra-operative CSF leak orsever prolapse of arachnoid
      membrane. Stage II was performed in 80 patients (33.3%) with either leak grade
      1(73 patients) or grade 0 with severe prolapse of the suprasellar components
      induced in the sella (2 cases) or inwhom extra-pseudocapsular dissection
      performed (5 cases). Stage III was performed in 34 cases (14.2%) witheither CSF
      leak grade 2 (29 patients) or grade 1 with simultaneous severe destruction or
      removal of sellar floorlaterally, superiorly or inferiorly (5 patients) which
      made it impossible to place the fascia underlay to the bone.A minimum of 18
      months follow-up showed development of 2 CSF leaks (0.8%), one pneumocephalus
      (0.4%)and 2 meningitis (0.8%) cases. CONCLUSION: Given the low postoperative CSF
      leak rate, we demonstrated that our adopted sellar reconstructionstrategy
      focusing mostly on the adopted intra-operative CSF leak grading system is safe
      and useful forovercoming devastating complications like postoperative CSF leaks.

PMID- 24926180
TI  - Effects of ageing on speed and temporal resolution of speech stimuli in older
      adults.
AB  - BACKGROUND: According to previous studies, most of the speech recognition
      disorders in older adults are theresults of deficits in audibility and auditory
      temporal resolution. In this paper, the effect of ageing on timecompressedspeech
      and auditory temporal resolution by word recognition in continuous and
      interrupted noisewas studied. METHODS: A time-compressed speech test (TCST) was
      conducted on 30 young and 32 older adults with normalhearing thresholds. Lists of
      monosyllabic words were used at three time compression ratios. Auditory
      temporalresolution was determined by measuring the monosyllabic word recognition
      score (WRS), in the presence ofcontinuous and interrupted noise, at three signal
      to-noise ratios (S/Ns). RESULTS: There was a significant difference in TCST
      scores at the three compression ratios within and betweenyoung and older adult
      none (p< 0.001). Similar results were obtained in WRSs at the three S/Ns in the
      presenceof interrupted and continuous noise (p< 0.001), and in the degree of
      auditory temporal resolution(p=0.007). A significant correlation was found
      between the level of test difficulty of TCST with WRSs in bothyoung (r = 0.549,
      P=0.002) and older adults (r= 0.531, P=0.003). CONCLUSION: Our results showed
      that ageing remarkably affects the processing of fast speech stimuli and
      temporalresolving ability. These results are more supportive of the effect of
      ageing on speech perception than onloss of hearing.

PMID- 24926181
TI  - The association between dietary antioxidant intake and semen quality in infertile
      men.
AB  - BACKGROUND: Oxidative stress is detrimental to semen quality and has a
      significant role in the etiology of malesubfertility. METHODS: Dietary intake of
      antioxidants were compared between thirty two men with oligolastheno/
      teratazoospermic(cases) and 32 normospermic volunteers (controls) attending
      fertility clinic in Mirza Koochak-khanHospital in Tehran, Iran. All participants
      were nonsmokers and matched according their age and Body MassIndex (BMI).
      Nutrient consumption was calculated using a semi- quantitative food frequency
      questionnaire.Semen samples were collected and were assessed by measuring volume,
      concentration, motility and morphology. RESULTS: infertile subjects had a
      significantly lower intake of zinc and folate compare to control ones(p<0.001).
      Dietary intake of vitamin C and E was lower than recommended values in 59.4% of
      case group thatwas significantly different from control ones (p<0.05). In control
      group, 36.4 and 40.9% of participants had insufficientdietary intake of vitamin C
      and E, respectively. Significant correlations were found between folate(r=0.5,
      p<0.001), zinc (r=0.6, p<0.001) and percentage of motility and also between
      vitamin E and morphology(r=0.3, p=0.03), zinc and concentration (r=0.4, p=0.004)
      in all participants. CONCLUSION: summary, a low intake of folate, zinc, and
      vitamin E were related to poor sperm concentrationand motility.

PMID- 24926182
TI  - Treatment of segmental vitiligo with normal-hair follicle autograft.
AB  - BACKGROUND: Segmental vitiligo is a small subset albeit persistent form of focal
      vitiligo with dermatomal distributionand resistant to medical therapy. In recent
      years, surgical therapy as hair follicle autograft transplantationhas been a hot
      topic in management of segmental vitiligo. In this study, we evaluated the
      efficacy of thismethod in segmental vitiligo lesions. METHODS: The study
      recruited 10 patients who suffered from resistant segmental vitiligo to evaluate
      the effectof transplantation of pigmented hair follicles on re-pigmentation of
      the affected area. In this method, one or twopunched-biopsy skin sample with a
      diameter of 5mm were harvested from occipital area of the scalps. Graftswere
      trimmed and divided into the follicular segments with at least one follicle in
      the interior and then insertedin the depigmented areas. Follow-up plan studies
      were scheduled to evaluate presence of pigmentation in theperifollicular areas.
      RESULTS: After 2 weeks, re-pigmentation was detectable surrounding the grafted
      hair follicles in 60 % of thecases. After 6 months, all of the patients had
      detectable re-pigmented area of about 2-9 mm. CONCLUSION: giving the surprising
      result of the study, hair follicle autograft transplant is an effective
      treatmentoption in the persistent segmental vitiligo.

PMID- 24926183
TI  - Marjolin's ulcer: clinical and pathologic features of 83 cases and review of
      literature.
AB  - BACKGROUND: Marjolin's ulcer is a rare, aggressive condition that arises on
      chronic skin lesions and diseases. Inthis article, we will report 83 cases of
      this disease. METHODS: Retrospectively, we retrieved 83 records of patients with
      cancer arising from chronic skin conditions.Data concerning demography, type of
      original skin insult, time interval between original lesion and cancer,cancer
      histology, and lymph node involvement were recorded. RESULTS: The mean age was
      55.30 years (range: 21-90). There were 51 males (61.5%) and 32 females
      (38.5%).Foot was the most prevalent site of primary skin lesion (49.4%) followed
      by scalp (15.6%). Original skin insultswere burn (87.9%), osteomyelitis (2.4%),
      radiation (2.4%), electrical burn (1.2%), surgical scar (2.4%),pemphigus (1.2%),
      bite (1.2%), and bed sore (1.2%). Histologic diagnosis were well differentiated
      SCC(38.6%), SCC, differentiation not reported (24.1%), moderately differentiated
      SCC (13.2%), BCC (9.6%), poorlydifferentiated SCC (6.0%), melanoma (2.4%),
      verrucous carcinoma (2.4%), MFH (1.2%), mucoepidermoidcarcinoma (1.2%), and
      leiomyosarcoma (1.2%). Most of the cases occurred more than 20 years after the
      initialskin insult. There were 6 (7.2%) cases that developed within 1 year (acute
      Marjolin's Ulcer). Forty three patients(69.3%) had palpable regional lymph nodes.
      CONCLUSION: Data in this series were in confirmation with many other reports.
      Marjoln's ulcer should be consideredas a significant post-skin injury
      complication.

PMID- 24926184
TI  - Review of the training program of pediatric residents: is it appropriate for
      their future careers?
AB  - BACKGROUND: Training of pediatric residents is a dynamic process which should be
      changed as the nature andepidemiology of pediatric diseases change. In this
      study, we compared the training program of the pediatric residentswith the
      disorders of the pediatric patients who had referred to pediatric offices.
      METHODS: The study was conducted in pediatric offices in Shiraz, South of Iran.
      The main complaints of all thepatients who were referred to these offices in the
      first 3 days of the four seasons of the year were recorded. Finally,descriptive
      statistics was used to determine the frequency of different complaints among
      these patients. RESULTS: There are 58 Pediatrics offices in Shiraz and 37 offices
      completed the questioners (64%). The mostfrequent complaints of the patients were
      related to infections, especially respiratory and gastrointestinal
      ones.Nutritional and growth problems were other frequent complaints. Nonetheless,
      a high number of the patientswere referred due to skin, eye, or ear problems or
      for check up of the baby. CONCLUSION: There is an important training-practice
      problem in the curriculum of pediatric residents. Thus, wesuggest decreasing the
      periods of inpatient subspecialty training and increasing the period of
      outpatient dermatology,ophthalmology, otolaryngology, and well-baby clinics.

PMID- 24926185
TI  - Harlequin ichthyosis in a neonate born with assisted reproductive technology: a
      case report.
AB  - Harlequin ichthyosis is a rare and the most severe form of congenital ichthyosis.
      Although prenatal diagnosis isdifficult for this disorder, recently, this
      obstacle has markedly improved with the use of DNA-based prenataldiagnosis. Here
      in, we presented a neonate with harlequin ichthyosis born by assisted
      reproductive technology(ART). In this case, the diagnosis of harlequin ichthyosis
      was not established by conventional prenatal screening. 

PMID- 24926186
TI  - Multiple lumbar vertebral fractures following a single idiopathic seizure in an
      otherwise healthy patient; a case report.
AB  - It has been reported that fractures are more common in epileptic patients
      relative to the general population.Seizures by repeated muscular contractions can
      increase fracture risk throughout the skeleton, but the reportedpapers about non
      traumatic vertebral fractures following a single episode of seizure are rare and
      mostly locatedin thoracic spine with only one or two vertebral fracture. The case
      we reported here was a 42 year old otherwisehealthy man who had three vertebral
      fractures due to a single idiopathic seizure affected the lumbar region withno
      previous history of underlying disease, trauma, or drug use. 

PMID- 24926188
TI  - Role of matrix metalloproteinases (MMPs) and MMP inhibitors on intracranial
      aneurysms: a review article.
AB  - Cerebrovascular disease is one of the leading causes of death in the world, and
      about one-fourth of cerebrovasculardeaths are due to ruptured cerebral aneurysms
      (CA). Hence it is important to find a way to reduce aneurysmformation and its
      subsequent morbidity and mortality. Proteolytic activity capable of lysing
      gelatin hasbeen shown to be increased in aneurysm tissue and expression of
      plasmin, membrane-type matrix metalloproteinase-1(MT1-MMP), and matrix
      metalloproteinase-2 (MMP-2) in aneurysmal wall is more than what we observein
      normal cerebral arteries. MMP inhibitors such as doxycycline and statins may
      prohibit aneurysm formationand growth. MMPs are important in tissue remodeling
      associated with various physiological and pathologicalprocesses such as
      morphogenesis, angiogenesis, apoptosis and tissue repair. In this article we
      review therole of MMPs and MMP inhibitors in formation of aneurysm. 

PMID- 24926187
TI  - Response-oriented measuring inequalities in Tehran: second round of UrbanHealth
      Equity Assessment and Response Tool (Urban HEART-2), concepts and framework.
AB  - BACKGROUND: Current evidence consistently confirm inequalities in health status
      among socioeconomic none, gender,ethnicity, geographical area and other social
      determinants of health (SDH), which adversely influence health ofthe population.
      SDH refer to a wide range of factors not limited to social component, but also
      involve economic, cultural,educational, political or environmental problems.
      Measuring inequalities, improving daily living conditions, andtackling
      inequitable distribution of resources are highly recommended by international SDH
      commissioners in recentyears to 'close the gaps within a generation'. To measure
      inequalities in socio-economic determinants and core healthindicators in Tehran,
      the second round of Urban Health Equity Assessment and Response Tool (Urban HEART
      2)was conducted in November 2011, within the main framework of WHO Centre for
      Health Development (Kobe Centre). METHOD: For 'assessment' part of the project,
      65 indicators in six policy domains namely 'physical and infrastructure','human
      and social', 'economic', 'governance', 'health and nutrition', and also
      'cultural' domain were targetedeither through a population based survey or using
      routine system. Survey was conducted in a multistage random
      sampling,disaggregated to 22 districts and 368 neighborhoods of Tehran, where
      data of almost 35000 households(118000 individuals) were collected. For
      'response' part of the project, widespread community based development(CBD)
      projects were organized in all 368 neighborhoods, which are being undertaken
      throughout 2013. CONCLUSION: Following the first round of Urban HEART project in
      2008, the second round was conducted to trackchanges over time, to
      institutionalize inequality assessment within the local government, to build up
      community participationin 'assessment' and 'response' parts of the project, and
      to implement appropriate and evidence-based actionsto reduce health inequalities
      within all neighborhoods of Tehran.

PMID- 24926189
TI  - Thermoresponsive Polyphosphazene-Based Molecular Brushes by Living Cationic
      Polymerization.
AB  - A series of polyphosphazenes with molecular brush type structures have been
      prepared with controlled molecular weights and narrow polydispersities. The
      polymers show lower critical solution temperatures (LCST) between 18 and 90 
      degrees C, which can be easily tailored by choice of side-substituent to suit the
      required application. A temperature triggered self-assembly is observed to give
      stable colloidal aggregates with dimensions in the region of 100-300 nm.

PMID- 24926190
TI  - Acquisition of Negation and Quantification: Insights From Adult Production and
      Comprehension.
AB  - Inspired by adult models of language production and comprehension, we investigate
      whether children's nonadult interpretation of ambiguous negative quantified
      sentences reflects their sensitivity to distributional patterns of language use.
      Studies 1 and 2 show that ambiguous negative quantified sentences of the sort
      typically used in acquisition studies are strongly avoided in adult production
      and are judged as poor alternatives by adults. Corpus Studies 3 and 4 show that
      children and adults overwhelmingly use quantifiers and negation in ways that
      promote one interpretation of these ambiguous quantified sentences over others.
      We argue that these patterns guide children's ambiguity resolution processes and
      explain children's interpretations of ambiguous quantified sentences. The origin
      of distributional patterns in adult production processes is discussed.

PMID- 24926191
TI  - Tear film dynamics with evaporation, wetting, and time-dependent flux boundary
      condition on an eye-shaped domain.
AB  - We study tear film dynamics with evaporation on a wettable eye-shaped ocular
      surface using a lubrication model. The mathematical model has a time-dependent
      flux boundary condition that models the cycles of tear fluid supply and drainage;
      it mimics blinks on a stationary eye-shaped domain. We generate computational
      grids and solve the nonlinear governing equations using the OVERTURE
      computational framework. In vivo experimental results using fluorescent imaging
      are used to visualize the influx and redistribution of tears for an open eye.
      Results from the numerical simulations are compared with the experiment. The
      model captures the flow around the meniscus and other dynamic features of human
      tear film observed in vivo.

PMID- 24926192
TI  - Melanocytoma of the ciliary body misdiagnosed as iridodialysis.
AB  - A 62-year-old female presented to our institution with dimness of vision in her
      right eye. On examination, her best corrected visual acuity was 20/100 in the
      right eye. The intraocular pressures were 14 mmHg in both eyes. Slit-lamp
      examination revealed nuclear sclerotic cataracts bilaterally and iridodialysis in
      her right eye. Seven days after the first visit, cataract surgery was performed
      without any complications. One year later, she presented to our institution with
      acute visual loss and ocular pain in the right eye. Best corrected visual acuity
      of the right eye was light perception and the intraocular pressure was 44 mmHg.
      Slit-lamp examination revealed a ciliary body mass with widespread pigment
      dispersion in the anterior segment. Due to no useful vision and uncontrolled
      pain, enucleation of the right eye was performed. Histopathologic examination
      revealed a melanocytoma of the ciliary body. 

PMID- 24926194
TI  - Once-weekly albiglutide in the management of type 2 diabetes: patient
      considerations.
AB  - This review describes the pharmacologic, pharmacokinetic, and pharmacodynamic
      properties of albiglutide, as well as its clinical efficacy and safety.
      Albiglutide is a novel, once-weekly, injectable glucagon-like peptide-1 receptor
      agonist for the treatment of type 2 diabetes. The European Commission recently
      granted marketing authorization for the drug in the European Union and on April
      15, 2014, the US Food and Drug Administration approved albiglutide (TanzeumTM
      [GlaxoSmithKline LLC, Wilmington, DE, USA]) to improve glycemic control in adults
      with type 2 diabetes. Albiglutide has been studied in Phase I, II, and III
      clinical trials. In the Phase III clinical trials, known as the Harmony series,
      weekly dosing of albiglutide demonstrated reductions in fasting plasma glucose,
      postprandial plasma glucose, and glycated hemoglobin, and was associated with
      weight loss. In all phases of the clinical trials, albiglutide administered once
      weekly showed a safety and tolerability profile similar to that of placebo, with
      mild gastrointestinal-related complaints and injection site erythema being the
      most commonly encountered adverse effects. Compared with pioglitazone and
      liraglutide, albiglutide has been shown to be clinically less effective. However,
      it offers the benefit of weight loss that pioglitazone does not, with fewer
      gastrointestinal side effects than liraglutide. As guidelines continue to
      advocate for patient-centered treatment strategies, once-weekly albiglutide will
      be an important addition to the growing armamentarium of treatment options for
      adults with type 2 diabetes needing target glycemic control. 

PMID- 24926195
TI  - Social phobia in Parkinson's disease: Prevalence and risk factors.
AB  - OBJECTIVE: We aimed to investigate the frequency of social phobia in patients
      with Parkinson's disease (PD). In addition, we explored the relationship between
      social phobia and the clinical characteristics of PD, and the frequency of
      comorbid psychiatric disorders in PD patients. METHODS: This study included 80
      consecutive patients with PD admitted to the Parkinson's disease and Movement
      Disorders Clinic at the Erenkoy Research and Training Hospital for Neurologic and
      Psychiatric Disorders, Istanbul, Turkey and used demographic and clinical data.
      The PD patients were evaluated during the "on state", using the Hoehn and Yahr
      scale, the Unified Parkinson's Disease Rating Scale, and the Schwab England
      Activities of Daily Living Scale. Psychiatric evaluations were conducted using
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      structured clinical interview, the Liebowitz Social Anxiety Scale (LSAS), and the
      Hamilton Depression Rating Scale. RESULTS: Social phobia was diagnosed in 42.5%
      of PD patients. Social phobia was comorbid with depression in 20 patients
      (58.8%), generalized anxiety disorder in 18 patients (52.9%), and panic disorder
      in six patients (17.6%). Social phobia was more frequent in males, early-onset
      PD, patients with a long duration of disease, the presence of postural
      instability, and with the use of a high Levodopa equivalent daily dose. A
      logistic regression analysis revealed the predictive factors of social phobia to
      be the sex of the patient (more frequent in males) and the presence of postural
      instability. There was a statistically significantly negative correlation between
      the LSAS score and the age of disease onset (r=-0.503; P=0.002) and a positive
      correlation between LSAS score and the duration of disease (r=0.374; P=0.023).
      CONCLUSION: Social phobia is frequently observed in PD patients. Therefore, the
      assessment of PD patients should always include psychiatric evaluations,
      particularly for social phobia. The early detection and treatment of social
      phobia in PD patients is very important for the quality of life of patients as
      well as caregivers.

PMID- 24926196
TI  - Disease progression model for Clinical Dementia Rating-Sum of Boxes in mild
      cognitive impairment and Alzheimer's subjects from the Alzheimer's Disease
      Neuroimaging Initiative.
AB  - BACKGROUND: The objective of this analysis was to develop a nonlinear disease
      progression model, using an expanded set of covariates that captures the
      longitudinal Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores. These
      were derived from the Alzheimer's Disease Neuroimaging Initiative ADNI-1 study,
      of 301 Alzheimer's disease and mild cognitive impairment patients who were
      followed for 2-3 years. METHODS: The model describes progression rate and
      baseline disease score as a function of covariates. The covariates that were
      tested fell into five groups: a) hippocampal volume; b) serum and cerebrospinal
      fluid (CSF) biomarkers; c) demographics and apolipoprotein Epsilon 4 (ApoE4)
      allele status; d) baseline cognitive tests; and e) disease state and
      comedications. RESULTS: Covariates associated with baseline disease severity were
      disease state, hippocampal volume, and comedication use. Disease progression rate
      was influenced by baseline CSF biomarkers, Trail-Making Test part A score,
      delayed logical memory test score, and current level of impairment as measured by
      CDR-SB. The rate of disease progression was dependent on disease severity, with
      intermediate scores around the inflection point score of 10 exhibiting high
      disease progression rate. The CDR-SB disease progression rate in a typical
      patient, with late mild cognitive impairment and mild Alzheimer's disease, was
      estimated to be approximately 0.5 and 1.4 points/year, respectively. CONCLUSIONS:
      In conclusion, this model describes disease progression in terms of CDR-SB
      changes in patients and its dependency on novel covariates. The CSF biomarkers
      included in the model discriminate mild cognitive impairment subjects as
      progressors and nonprogressors. Therefore, the model may be utilized for
      optimizing study designs, through patient population enrichment and clinical
      trial simulations.

PMID- 24926197
TI  - Nonepileptic seizures under levetiracetam therapy: a case report of forced
      normalization process.
AB  - Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not
      associated with ictal electrical discharges in the brain. NES constitute one of
      the most important differential diagnoses of epilepsy. They have been recognized
      as a distinctive clinical phenomenon for centuries, and
      video/electroencephalogram monitoring has allowed clinicians to make near-certain
      diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the
      preponderance of a psychiatric/psychological context, they may have an iatrogenic
      origin. We report a patient with NES precipitated by levetiracetam therapy; in
      this case, NES was observed during the disappearance of epileptiform discharges
      from the routine video/electroencephalogram. We discuss the possible mechanisms
      underlying NES with regard to alternative psychoses associated with the
      phenomenon of the forced normalization process. 

PMID- 24926198
TI  - Two cases of emotional disorder after middle cerebral artery infarction showing
      distinct responses to antidepressant treatment.
AB  - Many emotional disturbances such as post-stroke depression (PSD) and emotional
      incontinence (EI) commonly occur following cerebrovascular events. The efficacy
      of antidepressants for these conditions has been established but their comorbid
      treatment has not been well characterized. In the current study, the authors
      describe two cases of post-stroke emotional dysregulation; one case with EI; and
      the other with EI complicated by PSD. The authors describe their differential
      responses to treatment. Case 1 developed EI after an infarct due to occlusion of
      the penetrating branches of the left middle cerebral artery (MCA). Case 2
      developed both PSD and EI after right MCA stem occlusion. Both patients were
      initially treated with the selective serotonin reuptake inhibitor (SSRI)
      paroxetine. Case 1 reacted promptly to SSRI treatment. However, Case 2 had only a
      partial response to paroxetine, even after many months of treatment. Adjunctive
      therapy with low-dose aripiprazole was eventually added, resulting in complete
      improvement of both EI and PSD after 2 additional months of treatment. Thus, Case
      2 required a different treatment strategy than Case 1. These findings suggest
      that aripiprazole adjunctive therapy could be effective for some complex post
      stroke emotional disorders. 

PMID- 24926199
TI  - Pixantrone for the treatment of adult patients with relapsed or refractory
      aggressive non-Hodgkin B-cell lymphomas.
AB  - Treatment of patients with relapsed or refractory aggressive non-Hodgkin B-cell
      lymphoma remains an unmet clinical need, and the progressive myocardial toxicity
      related to cumulative, dose-dependent damage induced by anthracyclines represents
      a tricky issue in the planning of therapy. Pixantrone is a promising aza
      anthracenedione with reduced cardiotoxicity and significant antineoplastic
      activity, and has been investigated in solid and hematologic tumors in several
      Phase I, II, and III trials. The aim of this review is to summarize the data
      reported so far on pixantrone as a salvage therapy in relapsed/refractory non
      Hodgkin B-cell lymphoma. 

PMID- 24926200
TI  - Cyclic adenosine monophosphate-responsive element-binding protein activation
      predicts an unfavorable prognosis in patients with hepatocellular carcinoma.
AB  - AIM: To investigate the clinical significance of cyclic adenosine monophosphate
      responsive element-binding (CREB) and phosphorylated CREB (pCREB) expression in
      human hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Immunohistochemistry
      and Western blot analyses were performed to detect the expression and subcellular
      localizations of CREB and pCREB proteins in 130 pairs of HCC and adjacent
      nonneoplastic liver tissues. RESULTS: Both immunohistochemistry and Western blot
      analyses showed that the expression levels of CREB and pCREB proteins in HCC
      tissues were significantly higher than those in the adjacent nonneoplastic liver
      tissues (both P<0.001). In addition, the combined upregulation of CREB and pCREB
      proteins (CREB-high/pCREB-high) was significantly associated with serum alpha
      fetoprotein (P=0.02), tumor stage (P<0.001), and tumor grade (P=0.01). Moreover,
      HCC patients with CREB-high/pCREB-high expression showed shortest 5-year disease
      free survival and 5-year overall survival (both P<0.001). Furthermore, the
      multivariate survival analysis found that the combined upregulation of CREB and
      pCREB proteins may be an independent unfavorable prognostic factor for both 5
      year disease-free survival and 5-year overall survival (both P=0.01) in HCC.
      CONCLUSION: Our data indicate for the first time that the activation of the CREB
      protein may be associated with tumor progression in HCC, and may serve as a
      valuable marker of prognosis for patients with this malignancy.

PMID- 24926201
TI  - Regulation of tumor growth and metastasis: the role of tumor microenvironment.
AB  - The presence of abnormal cells with malignant potential or neoplastic
      characteristics is a relatively common phenomenon. The interaction of these
      abnormal cells with their microenvironment is essential for tumor development,
      protection from the body's immune or defence mechanisms, later progression and
      the development of life-threatening or metastatic disease. The tumor
      microenvironment is a collective term that includes the tumor's surrounding and
      supportive stroma, the different effectors of the immune system, blood platelets,
      hormones and other humoral factors. A better understanding of the interplay
      between the tumor cells and its microenvironment can provide efficient tools for
      cancer management, as well as better prevention, screening and risk assessment
      protocols. 

PMID- 24926202
TI  - Magnitude of HIV infection among older people in Mufindi and Babati districts of
      the Tanzania mainland.
AB  - INTRODUCTION: According to the 2011-2012 HIV and Malaria Indicator Survey, the
      prevalence of HIV infection in Tanzania is 5.1%, with limited information on its
      magnitude among older people, as the community believes that the elderly are not
      at risk. Consequently, little attention is given to the fight against HIV and
      AIDS in this group. The present study investigated the magnitude of HIV and AIDS
      infection among older people in rural and urban areas of the Tanzania mainland.
      SUBJECTS AND METHODS: The study was conducted in Mufindi and Babati districts of
      Iringa and Manyara regions, respectively, through multistage sampling procedures.
      Dried blood spot cards were used to collect blood samples for HIV testing among
      consenting participants. HIV testing was done and retested using different enzyme
      linked immunosorbent assay kits. RESULTS: A total of 720 individuals, 340 (47.2%)
      males and 380 (52.8%) females, were randomly selected, of whom 714 (99.2%)
      consented to HIV testing while six (0.8%) refused to donate blood. The age ranged
      from 50 to 98 years, with a mean age of 64.2 years. Overall, a total of 56 (7.8%)
      participants were HIV-positive. Females had a higher prevalence (8.3%) than males
      (7.4%), with Mufindi district recording the higher rate (11.3%) compared to the
      3.7% of Babati district. The prevalence was higher in the rural population (9.4%)
      compared to 6.4% of their urban counterparts. CONCLUSION: Although HIV/AIDS is
      considered a disease of individuals aged 15-49 years, the overall prevalence
      among the older people aged 50 years and above for Mufindi and Babati districts
      was higher than the national prevalence in the general population. These findings
      point to the need to consider strengthening interventions targeting older
      populations against HIV/AIDS in these districts while establishing evidence
      countrywide to inform policy decisions.

PMID- 24926203
TI  - A new device used in the restoration of kinematics after total facet
      arthroplasty.
AB  - Facet degeneration can lead to spinal stenosis and instability, and often
      requires stabilization. Interbody fusion is commonly performed, but it can lead
      to adjacent-segment disease. Dynamic posterior stabilization was performed using
      a total facet arthroplasty system. The total facet arthroplasty system was
      originally intended to restore the natural motion of the posterior stabilizers,
      but follow-up studies are lacking due to limited clinical use. We studied the
      first 14 cases (long-term follow-up) treated with this new device in our clinic.
      All patients were diagnosed with lumbar stenosis due to hypertrophy of the
      articular facets on one to three levels (maximum). Disk space was of normal
      height. The design of this implant allows its use only at levels L3-L4 and L4-L5.
      We implanted nine patients at the L4-L5 level and four patients at level L3-L4.
      Postoperative follow-up of the patients was obtained for an average of 3.7 years.
      All patients reported persistent improvement of symptoms, visual analog scale
      score, and Oswestry Disability Index score. Functional scores and dynamic
      radiographic imaging demonstrated the functional efficacy of this new implant,
      which represents an alternative technique and a new approach to dynamic
      stabilization of the vertebral column after interventions for spine
      decompression. The total facet arthroplasty system represents a viable option for
      dynamic posterior stabilization after spinal decompression. For the observed
      follow-up, it preserved motion without significant complications or apparent
      intradisk or adjacent-disk degeneration. 

PMID- 24926204
TI  - Stability of external and internal implant connections after a fatigue test.
AB  - OBJECTIVE: The objective of this study was to compare the torque and detorque
      values of screw intermediates of external hexagon, internal hexagon, and Morse
      taper implants in single restorations before and after mechanical cycling.
      MATERIALS AND METHODS: The study sample was divided into three groups (n = 10) as
      follows: group EH - external hexagon implant, group IH - internal hexagon
      implant, and group MT - Morse taper implant. Universal abutments were screwed on
      the implants, and metal crowns were cemented onto the abutment. The samples were
      submitted to a mechanical testing of 1 million cycles, with a frequency of 8
      cycles per second under a 400 N load. The application and registration of the
      screw torque (T0) and detorque (T1) values of the intermediate were performed
      before and after the test. The results were statistically evaluated by analysis
      of variance (ANOVA) and Tukey's test (alpha = 0.05). RESULTS: There was no
      difference between the values of T0 and T1 in the intra-group samples. However,
      the inter-group difference in T0 between the EH (12.8 N cm) and MT (18.6 N cm)
      groups and in T1 between the EH (10.4 N cm) and IH (13.8 N cm), EH and MT (19.4 N
      cm), and MT and IH (P = 0.001) groups were significant. The MT group showed a
      lower variation of T0 and T1. CONCLUSION: The internal implants, particularly MT,
      showed better stability in these cases when used for single restorations.

PMID- 24926205
TI  - Comparative assessment of marginal accuracy of grade II titanium and Ni-Cr alloy
      before and after ceramic firing: An in vitro study.
AB  - OBJECTIVE: The aims of the study are to assess the marginal accuracy of base
      metal and titanium alloy casting and to evaluate the effect of repeated ceramic
      firing on the marginal accuracy of base metal and titanium alloy castings.
      MATERIALS AND METHODS: Twenty metal copings were fabricated with each casting
      material. Specimens were divided into 4 groups of 10 each representing base metal
      alloys castings without (Group A) and with metal shoulder margin (Group B),
      titanium castings without (Group C) and with metal shoulder margin (Group D). The
      measurement of fit of the metal copings was carried out before the ceramic firing
      at four different points and the same was followed after porcelain build-up.
      RESULTS: Significant difference was found when Ni-Cr alloy samples were compared
      with Grade II titanium samples both before and after ceramic firings. The
      titanium castings with metal shoulder margin showed highest microgap among all
      the materials tested. CONCLUSIONS: Based on the results that were found and
      within the limitations of the study design, it can be concluded that there is
      marginal discrepancy in the copings made from Ni-Cr and Grade II titanium. This
      marginal discrepancy increased after ceramic firing cycles for both Ni-Cr and
      Grade II titanium. The comparative statistical analysis for copings with metal
      collar showed maximum discrepancy for Group D. The comparative statistical
      analysis for copings without metal-collar showed maximum discrepancy for Group C.

PMID- 24926206
TI  - Lateral incisor agenesis, canine impaction and characteristics of supernumerary
      teeth in a South European male population.
AB  - OBJECTIVE: To assess the prevalence of lateral incisor agenesis impacted canines
      and supernumerary teeth in a young adult male population. MATERIALS AND METHODS:
      The panoramic radiographs of 1745 military students (mean age: 18.6 +/- 0.52
      years) who attended the Center of Aviation Medicine of the Armed Forces of Greece
      during the period 1997-2011 were initially analyzed for lateral incisor agenesis
      by two observers. After exclusion of the known orthodontic cases, a subgroup of
      1636 examinees (mean age: 18.6 +/- 0.44 years) was evaluated for canine impaction
      and supernumerary teeth. RESULTS: Twenty-eight missing lateral incisors were
      observed in 22 military students, indicating an incidence of 1.3% in the
      investigated population. No lateral incisor agenesis was detected in the
      mandibular arch. A prevalence rate of 0.8% was determined for canine impaction in
      the sample of young adults. The majority of impacted teeth (86.7%) were diagnosed
      in the maxillary arch. Thirty-five supernumerary teeth were observed in 24
      examinees (prevalence rate: 1.5%). The ratio of supernumerary teeth located in
      the maxilla versus the mandible was 2.2:1. The most common type of supernumerary
      tooth was the upper distomolar. CONCLUSION: The prevalence of lateral incisor
      agenesis, canine impaction, and supernumerary teeth ranged from 0.8 to 1.5% in
      the sample of male Greek military students.

PMID- 24926207
TI  - Are the low-shrinking composites suitable for orthodontic bracket bonding?
AB  - PURPOSE: To evaluate the shear bond strength (SBS), adhesive remnant index (ARI),
      and microleakage of low-shrinking and conventional composites used as an
      orthodontic bracket bonding adhesive. MATERIALS AND METHODS: A hundred twenty non
      caries human premolars, extracted for orthodontic purposes, were used in this
      study. Sixty of them were separated into two groups. Brackets were bonded to the
      teeth in the test group with Silorane (3M-Espe) and control group with Transbond
      XT (3M-Unitek). SBS values of these brackets were recorded in MPa using a
      universal testing machine. ARI scores were determined after the failure of
      brackets. The remaining 60 teeth were divided into two groups and microleakage
      was evaluated by the dye penetration method. Statistical analyses were performed
      by Wilcoxon, Pearson Chi-square, and Mann-Whitney U tests at P < 0.05 level.
      RESULTS: The mean SBS for Transbond XT was significantly greater than low
      shrinking composite (P < 0.001). Significant differences (chi(2) =29.60, P <
      0.001) were present between the two groups for the ARI scores. Microleakage
      values were lower in low-shrinking composite than in the control group, and this
      difference was found to be statistically significant (P < 0.001). CONCLUSIONS:
      Although low-shrinking composite produced insufficient SBS and ARI scores,
      microleakage values were lower in low-shrinking composite than in the control
      group on the etched enamel surfaces, when used as a bracket bonding composite.

PMID- 24926208
TI  - Self-etch bonding agent beneath sealant: Bond strength for laser-irradiated
      enamel.
AB  - OBJECTIVES: This study evaluated the in vitro shear bond strength (SBS) of a
      resin-based pit-and-fissure sealant (Fluroshield [F], Dentsply/Caulk) associated
      with either an etch-and-rinse (Adper Single Bond 2 [SB], 3M/ESPE) or a two-step
      self-etch adhesive system (Adper SE Plus [SE], 3M/ESPE) on Er: YAG laser
      irradiated enamel. MATERIALS AND METHODS: Seventeen sound third molar crowns were
      embedded in acrylic resin, and the mesial-distal enamel surfaces were flattened.
      The enamel sites were irradiated with a 2.94-MUm wavelength Er: YAG laser (120
      mJ, 4 Hz, noncontact mode/17 mm, 20 s). The specimens were randomly assigned to
      three groups according to the bonding technique: I - 37% phosphoric acid etching
      + SB + F; II - SE + F and III - F applied to acid-etched enamel, without an
      intermediate layer of bonding agent. In all of the groups, a 3-mm diameter enamel
      bonding site was demarcated and the sealant cylinders were bonded. After 24 hours
      in distilled water, the shear bond strength was tested at a crosshead speed of
      0.5 mm/minute. The data were analyzed by one-way ANOVA and Tukey's test. The
      debonded specimens were examined with a stereomicroscope to assess the failure
      modes. RESULTS: The mean SBS values in MPa were I = 6.39 (+/-1.44); II = 9.50 (+/
      2.79); and III = 5.26 (+/-1.82). No statistically significant differences were
      observed between groups I and III; SE/F presented a significantly higher SBS than
      that of the other groups (P = 0.001). With regard to the failure mode, groups I
      (65%) and II (75%) presented adhesive failures, while group III showed 50%
      adhesive failure. Cohesive failure did not occur. CONCLUSION: The application of
      the two-step self-etch bonding agent (Adper SE Plus) beneath the resin pit-and
      fissure sealant placement resulted in a significantly higher bond strength for
      the Er:YAG laser-irradiated enamel.

PMID- 24926209
TI  - Evaluation of number of roots and root anatomy of permanent mandibular third
      molars in a Korean population, using cone-beam computed tomography.
AB  - OBJECTIVE: The purpose of this study was to investigate the morphology and number
      of roots of Korean mandibular third molars, and to evaluate the prevalence of C
      shaped, two-rooted, and three-rooted mandibular third molars using cone-beam
      computed tomography (CBCT). MATERIALS AND METHODS: Serial axial CBCT images of
      the mandibles were gathered from 137 Korean patients. The total number of roots
      in the mandibular third molars of these patients was measured, and both the
      incidence and the correlations between left- and right-side occurrences, as well
      as between males and females, were analyzed. RESULTS: Most of the mandibular
      third molars either had two roots (56.5%) or one root (37.9%). There was no
      significant difference regarding the incidence of the different types of roots
      according to gender (female versus male) or topology (right versus left side). A
      higher percentage (80.5%) of the patients had similar root morphology on both
      sides. CONCLUSION: The morphology and number of 214 mandibular third molars were
      examined using CBCT. There was a high prevalence of two-rooted mandibular and one
      rooted mandibular third molars from this Korean population. Even though the
      anatomical variations in the mandibular third molars may not be high, these data
      regarding the occurrence and morphology of the roots will provide useful
      information to dentists performing these procedures.

PMID- 24926210
TI  - Quantitative and qualitative analysis of microorganisms in root-filled teeth with
      persistent infection: Monitoring of the endodontic retreatment.
AB  - OBJECTIVE: The aim of this study was to investigate in vivo microorganisms
      detected in root-filled teeth with post-treatment apical periodontitis and
      quantify colony-forming units (CFU) during endodontic retreatment. MATERIALS AND
      METHODS: Fifteen root-filled teeth had their previous gutta-percha removed and
      were randomly instrumented before being divided into three groups and medicated
      with either [Ca(OH)2 + 2% CHX gel], [Ca(OH)2 + 0.9% NaCl] or 2% CHX gel. Samples
      were taken after removal of gutta-percha (S1), after chemomechanical preparation
      using 2% CHX gel (S2), and after inter-appointment dressing (S3) for 7 or 14 days
      later. Cultivable bacteria recovered from infected root canals at the three
      stages were counted and identified by means of culture and PCR assay (16S rDNA).
      Quantitative data were statistically analyzed by using Mann-Whitney test in which
      pairs of groups were compared (P < 0.05). RESULTS: CFU counts decreased
      significantly from S1 to S2 (P < 0.05). No significant difference was found
      between S2 and S3 (P = 0.3093) for all three experimental groups. Chemomechanical
      preparation and intra-canal dressing promoted significant median reductions of
      99.61% and 99.57%, respectively, in the number of bacteria compared to S1
      samples. A total of 110 cultivable isolates were recovered by culture technique
      from 32 different species and 7 different genera. Out of the 13 target species
      specific primer of bacteria analyzed, 11 were detected during endodontic
      retreatment. CONCLUSION: The great majority of taxa found in post-treatment
      samples were Gram-positive bacteria, although Gram-negative bacteria were found
      by molecular methods. Moreover, our results showed that gutta-percha removal and
      chemomechanical preparation are effective for root canal disinfection, whereas
      additional intra-canal dressing did not improve disinfection.

PMID- 24926211
TI  - Effect of dietary boron on 5-fluorouracil induced oral mucositis in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of boron on 5
      fluorouracil (5-FU)-induced oral mucositis in rats. MATERIALS AND METHODS: Sixty
      four male Wistar albino rats were injected with 5-FU on days 1 and 3. The right
      cheek pouch mucosa was scratched with the tip of an 18-G needle, dragged twice in
      a linear movement, on days 3 and 5. The animals were randomly divided into two
      groups of 32: boron group (BG) and control group (CG). Rats in the CG did not
      receive any treatment, whereas the others were fed boron (3 mg.kg(-1).day(-1)) by
      gavage. The animals were sacrificed on day 3 (n = 8), 6 (n = 8), 9 (n = 8), and
      12 (n = 8), and the cheek pouch was removed for histopathological analysis.
      RESULTS: On day 3, both groups showed necrosis and active inflammation, but the
      inflammation was mild in CG and moderate in BG. On day 6, both BG and CG showed
      necrosis; in the CG, there was moderate inflammation, and in the BG, there was
      severe inflammation and granulation tissue around the necrotic area. On day 9, re
      epithelization began in both groups, and there were no differences between
      groups. Re-epithelization was complete in both groups on day 12. CONCLUSION: We
      found no beneficial effect of boron in healing oral mucositis. Additional
      research is warranted to elucidate the pathogenic inflammatory mechanisms
      involved in mucositis and the prophylactic and therapeutic roles of antioxidants.

PMID- 24926212
TI  - Hybridization quality and bond strength of adhesive systems according to
      interaction with dentin.
AB  - OBJECTIVE: To evaluate the hybridization quality and bond strength of adhesives
      to dentin. MATERIALS AND METHODS: Ten human molars were ground to expose the
      dentin and then sectioned in four tooth-quarters. They were randomly divided into
      5 groups according to the adhesive used: Two single-step self-etch adhesives -
      Adper Prompt (ADP) and Xeno III (XE), two two-step self-etching primer systems -
      Clearfil SE Bond (SE) and Adhe SE (ADSE), and one one-step etch-and-rinse system 
      Adper Single Bond (SB). Resin composite (Filtek Z250) crown buildups were made
      on the bonded surfaces and incrementally light-cured for 20 s. The restored tooth
      quarters were stored in water at 37 degrees C for 24 h and then sectioned into
      beams (0.8 mm(2) in cross-section). Maximal microtensile bond strength (MU-TBS)
      was recorded (0.5 mm/min in crosshead speed). The results were submitted to one
      way ANOVA and Tukey's test (alpha = 0.05). Thirty additional teeth were used to
      investigate the hybridization quality by SEM using silver methenamine or
      ammoniacal silver nitrate dyes. RESULTS: SE reached significantly higher MU-TBS
      (P < 0.05); no significance was found between ADSE and XE (P > 0.05), and between
      SB and ADP (P > 0.05); ADSE and XE were significantly higher than SB and ADP (P <
      0.05). The bonding interface of SB showed the most intense silver uptake. SE and
      ADSE showed more favorable hybridization quality than that observed for ADP and
      XE. CONCLUSIONS: The bond strength and hybridization quality were affected by the
      interaction form of the adhesives with dentin. The hybridization quality was
      essential to improve the immediate MU-TBS to dentin.

PMID- 24926213
TI  - Comparative study of surface microhardness of methacrylate-based composite resins
      polymerized with light-emitting diodes and halogen.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of polymerization
      with quartz-tungsten-halogen (QTH) and light-emitting diodes (LED) on the surface
      microhardness of eight commercially available light-polymerized, methacrylate
      based composite resins, with different filler particle composition (microfill,
      minifill, nanohybrids, and microhybrids) immediately after polymerization, after
      24 hours, and after three months of storage. MATERIALS AND METHODS: Eighty disk
      shaped specimens were prepared using a split Teflon mold (6 * 2 mm) and were
      irradiated with either the QTH (Elipar 2500; 600 mW/cm(2)) for 20 seconds or an
      LED (Bluephase G2; 1,200 mW/cm(2)) for 40 seconds. The microhardness values were
      recorded using a Vickers hardness tester at a 300 g load for 15 seconds,
      immediately after polymerization, after 24 hours, and after three months of dark
      aging in distilled water at 37 degrees C. Statistical analysis was performed
      using a two-way analysis of variance (ANOVA) and the Tukey's test. RESULTS: The
      baseline values demonstrated a significant effect of the composite and the
      interaction composite-LCU on the microhardness (P < 0.05). At 24 hours, only the
      composite variable showed a significant effect on the hardness values (P < 0.05).
      After three months, the composite, LCU, and the interaction composite-LCU all
      demonstrated a significant effect on the microhardness (P < 0.05). CONCLUSIONS:
      The effectiveness of polymerization, measured in terms of surface hardness, was
      shown to be dependent not only on the type of light curing unit, but also on the
      type of composite. Moreover, the choice of composite was shown to affect the
      performance of the light curing unit.

PMID- 24926215
TI  - The effect of different organic solvents on the degradation of restorative
      materials.
AB  - OBJECTIVE: To evaluate the solubility of three restorative materials exposed to
      the different endodontic solvents. MATERIALS AND METHODS: The organic solvents
      eucalyptus oil, xylol, chloroform, and orange oil, with distilled water as the
      control group was utilized. The restorative materials light-cured resin (Filtek
      Z250/3M ESPE), light-cured-resin-reinforced glass ionomer (Riva Light Cure
      LC/Southern Dental Industries SDI]) and resin-modified glass ionomer (Vitremer/3M
      ESPE) were analyzed. A total of 50 disks containing specimens (2 mm * 8 mm O)
      were prepared for each of the three classes of restorative materials, which were
      divided into 10 groups (n = 5) for immersion in eucalyptus oil, xylol,
      chloroform, orange oil or distilled water for periods of either 2 min or 10 min.
      The means of restorative material disintegration in solvents were obtained by the
      difference between the original preimmersion weight and the postimmersion weight
      in a digital analytical scale. Data were statistically analyzed by two-way
      analysis of variance while the difference between the materials was analyzed by
      Student-Newman-Keuls test. The significance level set at 0.05. RESULTS: Vitremer
      showed the highest solubility, followed by Riva LC, and these were statistically
      different from eucalyptus oil, xylol, chloroform, and distilled water (P < 0.05).
      Regarding the immersion time in solvents, there were no significant differences
      between the two tested periods (P > 0.05). CONCLUSIONS: The solvents minimally
      degraded the composite resin, although they did influence the degradation of both
      resin-modified glass ionomer resin and resin reinforced with glass ionomer.

PMID- 24926214
TI  - Risk factors and socioeconomic condition effects on periodontal and dental
      health: A pilot study among adults over fifty years of age.
AB  - OBJECTIVE: Observational studies on the association among systemic/general and
      oral cavity indices, tooth loss, periodontal conditions, and socioeconomic
      inequalities are to be still performed in the population of Southern Europe. This
      study aims to determine the extent of this relationship among Italian healthy
      adults 50 years of age and above. MATERIALS AND METHODS: Socioeconomic and
      lifestyle characteristics, cardiovascular indicators, and systemic indices were
      examined by contrasting the dental indices among adult people of Northern Italy.
      Data were processed through correlation analysis, and multivariate analysis was
      carried out using seemingly unrelated regressions. RESULTS: A total of 118 adults
      50 years of age and above, after anamnesis, underwent systemic and dental
      examination. Their socioeconomic status was found to be inversely associated only
      with smoking and dental parameters. Unexpected outcomes between lifestyle and
      risk factors were detected. The statistical analysis showed an uneven correlation
      among dental indices and between those indices and the socioeconomic status, such
      as, a periodontal condition, apparently free from influences, unusually became
      worse as the socioeconomic status enhanced. CONCLUSIONS: The study outcomes
      indicate a relationship between tooth loss and conservative endodontic therapy,
      but they result in alternative choices. Nevertheless, the socioeconomic status
      has an inverse relationship with tooth loss and conservative endodontic therapy,
      but a direct relation with worsening of the periodontal condition. This pilot
      study highlights a need for the public health administration to adopt a
      socioeconomic assessment not only based on the household income, but also to
      accordingly improve its therapeutic course.

PMID- 24926216
TI  - The effects of three different mouth rinses in a 4-day supragingival plaque
      regrowth study.
AB  - OBJECTIVE: This study compares the effects of three different mouth rinses with
      respect to reducing Streptococcus mutans (S. mutans) colony counts on the teeth
      and tongue surfaces. MATERIALS AND METHODS: In this study, comparison tests using
      the alcohol-free 0.1% chlorhexidine mouth rinse, alcohol-containing essential oil
      mouth rinse, and alcohol-free essential oil-containing mouth rinse were
      conducted. Patients were instructed to avoid mechanical cleaning with either a
      toothbrush or toothpick for 4 days. The first samples were collected from teeth
      surfaces and the dorsum of the tongue after a professional cleaning, and the
      second samples were collected after a 4-day plaque re-growth period. The
      supragingival plaque from the buccal surfaces of teeth #11, 14, 31, 34 as well as
      samples from the dorsum of the tongue, were assessed using the Dentocult((r))
      strips. RESULTS: The Listerine((r)) and Ondrohexidine((r)) groups did not show
      any statistically significant differences between the values of the two samples
      (P = 0.734, P = 0.307). The MC((r)) group and the control group showed
      significantly higher results than the first sample values. The effectiveness of
      the mouth rinses on S. mutans colony counts from the teeth surfaces were higher
      in the Listerine((r)), Ondrohexidine((r)), and Mouthwash Concentrate((r)) groups.
      The difference between the first and second samples of the S. mutans colony
      counts from the tongue surface was found to be statistically significant, and S.
      mutans colony counts were higher than the first sample (P = 0.015). CONCLUSION:
      Alcohol and essential oil-containing Listerine((r)) mouth rinse, alcohol-free
      Ondrohexidine((r)), alcohol-free essential oil-containing MC((r)) mouth rinse had
      the same effect on S. mutans counts, higher than the 1% alcohol solution on teeth
      surface. They had the ability to maintain the S. mutans counts at the same level
      for 4 days in patients who did not perform any mechanical oral hygiene regimen.

PMID- 24926217
TI  - Fluid flow evaluation of coronal microleakage intraorifice barrier materials in
      endodontically treated teeth.
AB  - OBJECTIVE: The objective of this study was to compare the coronal microleakage
      intraorifice barrier materials, called CoroSeal (CS), fissur sealant (FS),
      flowable composite FC, and policarboksilate cement (PC), by using the
      computerized fluid filtration method. MATERIALS AND METHODS: Fifty freshly
      extracted, single-canal human maxillary central teeth were used in this study.
      The teeth were decoronated to a standardized root length of 15 mm. After
      preparation and irrigation, all the teeth were obturated with gutta-percha and AH
      Plus. In all teeth, the coronal 2 mm of root filling was removed and replaced
      with one of the intraorifice barriers. According to intraorifice barriers, teeth
      were divided randomly into 4 experimental groups (n = 10) and 2 control groups (n
      = 5). Group 1: CS; Group 2: FS; Group 3: FC; and Group 4: PC. POSITIVE CONTROL
      GROUP: No barrier material was used. NEGATIVE CONTROL GROUP: Roots were
      completely coated with the nail polish, including the orifice. Leakage was
      evaluated by using a computerized fluid filtration model. Differences in fluid
      filtration among groups were subjected to statistical analysis using the Kruskal
      Wallis Test and multiple comparisons test. RESULTS: A value of P < 0.05 was
      statistically significant. Statistical analysis has indicated that the CS leaked
      significantly less than other groups (P < 0.05). There was a significant
      difference between FS and PC (P < 0.05), in contrast there was no significant
      difference between FS and FC (P > 0.05). CONCLUSIONS: Using the CS material as an
      intraorrifice barrier material reduced amount of microleakage as compared with
      FS, FC, and PC.

PMID- 24926218
TI  - Subpontic osseous hyperplasia: Three case reports and literature review.
AB  - Subpontic osseous hyperplasia (SOH) is an ectopic growth of bone occurring on the
      edentulous ridge beneath a fixed partial denture. The aim of this article is to
      present three patients with SOH with long-term follow-up and to make a current
      overview of the literature. Presented maxillary SOH is the second case in the
      dental literature. Intraorally the lesions were bone-hard and painless swellings
      in the subpontic space. Radiographically, the maxillary case was a nodular bone
      growth having similar radiodensity and trabeculation to the adjacent bone with a
      thin radiopaque border. Mandibular cases were bony growths, which were more
      radiopaque than the adjacent alveolar ridge. Follow-up radiographs revealed
      regression in two of the cases. Clinicians should take care not to cause the
      possible etiologies of SOH such as functional stresses and chronic irritation by
      the prosthetic treatments and be aware of SOH does not usually require treatment
      or a biopsy. 

PMID- 24926219
TI  - Shallow localized gingival recession defects treated with modified coronally
      repositioned flap technique: A case series.
AB  - OBJECTIVES: Various coronally repositioned flap (CRF) techniques have been
      proposed for coverage of gingival recession defects. Although CRF has several
      modifications all of them needs vertical or oblique external releasing incisions
      for treatment of localized gingival recession defects. The aim of present article
      was to evaluate the effectiveness of a modification of the new CRF procedure
      without any releasing incision for treatment of shallow localized gingival
      recession defects. CONCLUSION: Shallow localized gingival recession defects can
      be treated with modified coronally repositioned flap technique successfully.

PMID- 24926220
TI  - Galvanic gold plating for fixed dental prosthesis.
AB  - Metal ceramic partial fixed dental prostheses have been commonly used for the
      replacement of missing teeth for many years. Because of an increase in the price
      of gold, base metal alloys have been the choice of alloy for the fabrication of
      metal ceramic restorations in many dental clinics. Some major disadvantages of
      base metals are their corrosion and the dark coloration they may cause at the
      crown margins. This article describes a galvanic gold-plating technique, which is
      used to minimize corrosion and improve the esthetics of metal ceramic
      restorations fabricated with Cr-Co base metal alloys. This technique involves the
      deposition of a 6 MUm to 8 MUm 24 K gold layer directly onto the Cr-Co cast
      prosthesis framework. The technique improves metal surface properties, making
      them more biocompatible and usable, however, requires additional equipment and
      experienced laboratory technicians. Clinical studies should be performed to
      corroborate the long term success of this technique. 

PMID- 24926221
TI  - Bone regeneration with plasma-rich-protein following enucleation of traumatic
      bone cyst.
AB  - Traumatic bone cyst is an uncommon non-epithelium lined cavity and is seen
      frequently in young individuals. The lesion occurs more commonly in the mandible,
      involving the posterior region. It is generally asymptomatic and is diagnosed on
      routine radiographic examination. The cystic cavity is usually empty and there is
      scanty material for histological examination. Surgical curettage is usually done
      and recurrence is rare. A case of traumatic bone cyst occurring in the anterior
      region of mandible in a young boy is presented. Following surgical intervention,
      plasma-rich-protein was placed in the cystic cavity. The lesion showed
      progressive resolution and bone regeneration of the cystic cavity within a short
      period of time. 

PMID- 24926222
TI  - Repair of a fractured implant overdenture gold bar: A clinical and laboratory
      technique report.
AB  - This clinical report explains a convenient, efficient, yet effective alternative
      for management of fractured substructure cast bars for implant-retained
      overdentures. The technique allows the fracture to be repaired at low cost and
      short time without remaking the substructure and the denture and further allowing
      the patient to keep their denture. The report sketches the clinical and
      laboratory procedures involved in the repair. 

PMID- 24926223
TI  - Documenting biomedical research; some bitter aspects.

PMID- 24926224
TI  - The Effect of Maternal Depressive Symptoms and Early Maternal Feeding Behavior on
      Later Infant Feeding Behavior.
AB  - Adaptive maternal feeding behaviors are sensitive and responsive to the infant
      and support the infant's participation in feeding. Adaptive infant behaviors help
      the infant to participate in the feeding within developmental capacities and to
      interact in a positive manner with the mother. Therefore, the purpose of this
      study was to explore the contribution of the adaptiveness of early maternal
      feeding behavior to the adaptiveness of later infant feeding behavior, accounting
      for maternal depressive symptoms and neonatal health. Thirty-seven premature
      infants and their mothers were assessed in the special care nursery just before
      discharge and in their homes at 4 months postterm age. The adaptive quality of
      maternal and infant behavior was assessed using the Parent-Child Early Relational
      Assessment. Maternal depressive symptoms were assessed using the Center for
      Epidemiological Study-Depression Scale. Infant health was assessed using the
      Neonatal Health Index. Linear regression analyses revealed that the adaptiveness
      of maternal feeding behavior before special care nursery discharge contributed
      significantly to the adaptiveness of infant feeding behavior at 4 months postterm
      age, accounting for neonatal health and maternal depressive symptoms. Although
      further study of the relationship is needed, findings support development of
      interventions to enhance the adaptiveness of mothers' early feeding behaviors.

PMID- 24926225
TI  - Mixed Methods Research With Internally Displaced Colombian Gay and Bisexual Men
      and Transwomen.
AB  - We discuss the use of mixed methods research to further understanding of
      displaced Colombian gay and bisexual men and transwomen, a marginalized
      population at risk. Within the framework of communicative action, which calls for
      social change through egalitarian dialog, we describe how our multinational,
      interdisciplinary research team explored the subjective, objective, and social
      worlds of participants through life history interviews and surveys. We also
      describe the unique Colombian context, conscious efforts to establish egalitarian
      relationships among research team members, and efforts to disseminate and reflect
      on findings. Through discussion of our research process and results, we aim to
      demonstrate how mixed methods research can be utilized to facilitate noncoercive
      discourse and contribute to social change.

PMID- 24926226
TI  - Electrochemical characterization of sub-micro-gram amounts of organic
      semiconductors using scanning droplet cell microscopy.
AB  - Scanning droplet cell microscopy (SDCM) uses a very small electrolyte droplet at
      the tip of a capillary which comes in contact with the working electrode. This
      method is particularly interesting for studies on organic semiconductors since it
      provides localized electrochemical investigations with high reproducibility. One
      clear advantage of applying SDCM is represented by the very small amounts of
      material necessary (less than 1 mg). Organic materials can be investigated
      quickly and inexpensively in electrochemical studies with a high throughput. In
      the present study, thin layers of poly(3-hexylthiophene) (P3HT), which is one of
      the most often used material for organic solar cells, were deposited on ITO/glass
      as working electrodes in SDCM studies. The redox reactions in 0.1 M tetra(n
      butyl)ammonium hexafluorophosphate (TBAPF6) dissolved in propylene carbonate were
      studied by cyclic voltammetry and by electrochemical impedance spectroscopy. Two
      reversible, distinct oxidation steps of the P3HT were detected and their kinetics
      were studied in detail. The doping of P3HT increased due to the electrochemical
      oxidation and had resulted in a decrease of the film resistance by a few orders
      of magnitude. Due to localization on the sample various parameter combinations
      can be studied quantitatively and reproducibly.

PMID- 24926227
TI  - Investigation of the reduction process of dopamine using paired pulse
      voltammetry.
AB  - The oxidation of dopamine (DA) around +0.6V potential in anodic sweep and its
      reduction around -0.1V in cathodic sweep at a relatively fast scanning rate (300
      V/s or greater) have been used for identification of DA oxidation in fast-scan
      cyclic voltammetry (FSCV). However, compared to the oxidation peak of DA, the
      reduction peak has not been fully examined in analytical studies, although it has
      been used as one of the representative features to identify DA. In this study,
      the reduction process of DA was investigated using paired pulse voltammetry
      (PPV), which consists of two identical triangle-shaped waveforms, separated by a
      short interval at the holding potential. Especially, the discrepancies between
      the magnitude of the oxidation and reduction peaks of DA were investigated based
      on three factors: (1) the instant desorption of the DA oxidation product
      (dopamine-o-quinone: DOQ) after production, (2) the effect of the holding
      potential on the reduction process, and (3) the rate-limited reduction process of
      DA. For the first test, the triangle waveform FSCV experiment was performed on DA
      with various scanrates (from 400 to 1000 V/s) and durations of switching
      potentials of the triangle waveform (from 0.0 to 6.0 ms) in order to vary the
      duration between the applied oxidation potential at +0.6V and the reduction
      potential at -0.2V. As a result, the ratio of reduction over oxidation peak
      current response decreased as the duration became longer. To evaluate the effect
      of holding potentials during the reduction process, FSCV experiments were
      conducted with holding potential from 0.0V to -0.8V. We found that more negative
      holding potentials lead to larger amount of reduction process. For evaluation of
      the rate-limited reduction process of DA, PPV with a 1Hz repetition rate and
      various delays (2, 8, 20, 40 and 80ms) between the paired scans were utilized to
      determine how much reduction process occurred during the holding potential (
      0.4V). These tests showed that relatively large amounts of DOQ are reduced to DA
      during the holding potential. The rate-limited reduction process was also
      confirmed with the increase of reduction in a lower pH environment. In addition
      to the mechanism of the reduction process of DA, we found that the differences
      between the responses of primary and secondary pulses in PPV were mainly
      dependent on the rate-limited reduction process during the holding potential. In
      conclusion, the reduction process may be one of the important factors to be
      considered in the kinetic analysis of DA and other electroactive species in brain
      tissue and in the design of new types of waveform in FSCV.

PMID- 24926228
TI  - Spontaneous massive necrosis of hepatocellular carcinoma with narrowing and
      occlusion of the arteries and portal veins.
AB  - We herein present the case of a 77-year-old man who had fever and right
      hypochondriac pain. He visited his doctor and underwent contrast computed
      tomography (CT), and he was suspected to have a liver abscess. He received an
      antibiotic treatment and his symptoms soon disappeared, but the tumor did not get
      smaller and its density on contrast CT image got stronger. He underwent biopsy
      and moderately differentiated hepatocellular carcinoma (HCC) was found. Extended
      left hepatic and caudate lobectomy was performed. Histological examination showed
      moderately differentiated HCC with narrowing and occlusion both in the arteries
      and portal veins associated with mild chronic inflammation. The mechanisms of
      spontaneous regression of HCC, such as immunological reactions and tumor hypoxia,
      have been proposed. In our case, histological examination showed the same
      findings. However, the mechanism is complex, and therefore further investigations
      are essential to elucidate it. 

PMID- 24926229
TI  - Obturator hernia with ureteral entrapment.
AB  - Obturator hernia of the ureter is uncommon. Computed tomography of a 77-year-old
      woman with sudden-onset lower left abdominal pain and urinary symptoms showed an
      obturator hernia with ureteral entrapment. Obturator hernia is a diagnostic
      challenge because the hernial mass is very insidious. It should be suspected in
      emaciated, multiparous, elderly women presenting with unexplained pain in the
      groin, hip, thigh or knee. High levels of clinical suspicion of high-risk
      patients and recourse to investigation by computed tomography are important, as
      delay in diagnosis and treatment is associated with increased morbidity and
      mortality. 

PMID- 24926230
TI  - Phonemic restoration in developmental dyslexia.
AB  - The comprehension of fluent speech in one's native language requires that
      listeners integrate the detailed acoustic-phonetic information available in the
      sound signal with linguistic knowledge. This interplay is especially apparent in
      the phoneme restoration effect, a phenomenon in which a missing phoneme is
      "restored" via the influence of top-down information from the lexicon and through
      bottom-up acoustic processing. Developmental dyslexia is a disorder characterized
      by an inability to read at the level of one's peers without any clear failure due
      to environmental influences. In the current study we utilized the phonemic
      restoration illusion paradigm to examine individual differences in phonemic
      restoration across a range of reading ability, from very good to dyslexic
      readers. Results demonstrate that restoration occurs less in those who have high
      scores on measures of phonological processing. Based on these results, we suggest
      that the processing or representation of acoustic detail may not be as reliable
      in poor and dyslexic readers, with the result that lexical information is more
      likely to override acoustic properties of the stimuli. This pattern of increased
      restoration could result from a failure of perceptual tuning, in which unstable
      representations of speech sounds result in the acceptance of non-speech sounds as
      speech. An additional or alternative theory is that degraded or impaired
      phonological processing at the speech sound level may reflect architecture that
      is overly plastic and consequently fails to stabilize appropriately for speech
      sound representations. Therefore, the inability to separate speech and noise may
      result as a deficit in separating noise from the acoustic signal. 

PMID- 24926231
TI  - Direct reticular projections of trigeminal sensory fibers immunoreactive to CGRP:
      potential monosynaptic somatoautonomic projections.
AB  - Few trigeminal sensory fibers project centrally beyond the trigeminal sensory
      complex, with only projections of fibers carried in its sensory anterior
      ethmoidal (AEN) and intraoral nerves described. Fibers of the AEN project into
      the brainstem reticular formation where immunoreactivity against substance P and
      CGRP are found. We investigated whether the source of these peptides could be
      from trigeminal ganglion neurons by performing unilateral rhizotomies of the
      trigeminal root and looking for absence of label. After an 8-14 days survival,
      substance P immunoreactivity in the trigeminal sensory complex was diminished,
      but we could not conclude that the sole source of this peptide in the lateral
      parabrachial area and lateral reticular formation arises from primary afferent
      fibers. Immunoreactivity to CGRP after rhizotomy however was greatly diminished
      in the trigeminal sensory complex, confirming the observations of others.
      Moreover, CGRP immunoreactivity was nearly eliminated in fibers in the lateral
      parabrachial area, the caudal ventrolateral medulla, both the peri-ambiguus and
      ventral parts of the rostral ventrolateral medulla, in the external formation of
      the nucleus ambiguus, and diminished in the caudal pressor area. The nearly
      complete elimination of CGRP in the lateral reticular formation after rhizotomy
      suggests this peptide is carried in primary afferent fibers. Moreover, the
      arborization of CGRP immunoreactive fibers in these areas mimics that of direct
      projections from the AEN. Since electrical stimulation of the AEN induces
      cardiorespiratory adjustments including an apnea, peripheral vasoconstriction,
      and bradycardia similar to those seen in the mammalian diving response, we
      suggest these perturbations of autonomic behavior are enhanced by direct somatic
      primary afferent projections to these reticular neurons. We believe this to be
      first description of potential direct somatoautonomic projections to brainstem
      neurons regulating autonomic activity. 

PMID- 24926232
TI  - Simultaneous EEG-fMRI brain signatures of auditory cue utilization.
AB  - Optimal utilization of acoustic cues during auditory categorization is a vital
      skill, particularly when informative cues become occluded or degraded.
      Consequently, the acoustic environment requires flexible choosing and switching
      amongst available cues. The present study targets the brain functions underlying
      such changes in cue utilization. Participants performed a categorization task
      with immediate feedback on acoustic stimuli from two categories that varied in
      duration and spectral properties, while we simultaneously recorded Blood
      Oxygenation Level Dependent (BOLD) responses in fMRI and electroencephalograms
      (EEGs). In the first half of the experiment, categories could be best
      discriminated by spectral properties. Halfway through the experiment, spectral
      degradation rendered the stimulus duration the more informative cue.
      Behaviorally, degradation decreased the likelihood of utilizing spectral cues.
      Spectrally degrading the acoustic signal led to increased alpha power compared to
      nondegraded stimuli. The EEG-informed fMRI analyses revealed that alpha power
      correlated with BOLD changes in inferior parietal cortex and right posterior
      superior temporal gyrus (including planum temporale). In both areas, spectral
      degradation led to a weaker coupling of BOLD response to behavioral utilization
      of the spectral cue. These data provide converging evidence from behavioral
      modeling, electrophysiology, and hemodynamics that (a) increased alpha power
      mediates the inhibition of uninformative (here spectral) stimulus features, and
      that (b) the parietal attention network supports optimal cue utilization in
      auditory categorization. The results highlight the complex cortical processing of
      auditory categorization under realistic listening challenges. 

PMID- 24926233
TI  - Targeting GTPases in Parkinson's disease: comparison to the historic path of
      kinase drug discovery and perspectives.
AB  - Neurological diseases have placed heavy social and financial burdens on modern
      society. As the life expectancy of humans is extended, neurological diseases,
      such as Parkinson's disease, have become increasingly common among senior
      populations. Although the enigmas of Parkinson's diseases await resolution, more
      vivid pictures on the cause, progression, and control of the illness are emerging
      after years of research. On the molecular level, GTPases are implicated in the
      etiology of Parkinson's disease and are rational pharmaceutical targets for their
      control. However, targeting individual GTPases, which belong to a superfamily of
      proteins containing multiple members with a conserved guanine nucleotide binding
      domain, has proven to be challenging. In contrast, pharmaceutical pursuit of
      inhibition of kinases, which constitute another superfamily of proteins with more
      than 500 members, has been fairly successful. We reviewed the breakthroughs in
      the history of kinase drug discovery to provide guidance for the GTPase field. We
      summarize recent progress made in the regulation of GTPase activity. We also
      present an efficient and cost effective approach to drug screening, which uses
      multiplex flow cytometry and mixture-based positional scanning libraries. These
      methods allow simultaneous measurements of both the activity and the selectivity
      of the screened library. Several GTPase activator clusters were identified which
      showed selectivity against different GTPase subfamilies. While the clusters need
      to be further deconvoluted to identify individual active compounds, the method
      described here and the structure information gathered create a foundation for
      further developments to build upon. 

PMID- 24926234
TI  - Subcircuit-specific neuromodulation in the prefrontal cortex.
AB  - During goal-directed behavior, the prefrontal cortex (PFC) exerts top-down
      control over numerous cortical and subcortical regions. PFC dysfunction has been
      linked to many disorders that involve deficits in cognitive performance,
      attention, motivation, and/or impulse control. A common theme among these
      disorders is that neuromodulation of the PFC is disrupted. Anatomically, the PFC
      is reciprocally connected with virtually all neuromodulatory centers. Recent
      studies of PFC neurons, both in vivo and ex vivo, have found that subpopulations
      of prefrontal projection neurons can be segregated into distinct subcircuits
      based on their long-range projection targets. These subpopulations differ in
      their connectivity, intrinsic properties, and responses to neuromodulators. In
      this review we outline the evidence for subcircuit-specific neuromodulation in
      the PFC, and describe some of the functional consequences of selective
      neuromodulation on behavioral states during goal-directed behavior. 

PMID- 24926235
TI  - Neurotrophins and spinal circuit function.
AB  - Work early in the last century emphasized the stereotyped activity of spinal
      circuits based on studies of reflexes. However, the last several decades have
      focused on the plasticity of these spinal circuits. These considerations began
      with studies of the effects of monoamines on descending and reflex circuits. In
      recent years new classes of compounds called growth factors that are found in
      peripheral nerves and the spinal cord have been shown to affect circuit behavior
      in the spinal cord. In this review we will focus on the effects of neurotrophins,
      particularly nerve growth factor (NGF), brain derived neurotrophic factor (BDNF)
      and neurotrophin-3 (NT-3), on spinal circuits. We also discuss evidence that
      these molecules can modify functions including nociceptive behavior, motor
      reflexes and stepping behavior. Since these substances and their receptors are
      normally present in the spinal cord, they could potentially be useful in
      improving function in disease states and after injury. Here we review recent
      findings relevant to these translational issues. 

PMID- 24926236
TI  - Purines released from astrocytes inhibit excitatory synaptic transmission in the
      ventral horn of the spinal cord.
AB  - Spinal neuronal networks are essential for motor function. They are involved in
      the integration of sensory inputs and the generation of rhythmic motor outputs.
      They continuously adapt their activity to the internal state of the organism and
      to the environment. This plasticity can be provided by different neuromodulators.
      These substances are usually thought of being released by dedicated neurons.
      However, in other networks from the central nervous system synaptic transmission
      is also modulated by transmitters released from astrocytes. The star-shaped glial
      cell responds to neurotransmitters by releasing gliotransmitters, which in turn
      modulate synaptic transmission. Here we investigated if astrocytes present in the
      ventral horn of the spinal cord modulate synaptic transmission. We evoked
      synaptic inputs in ventral horn neurons recorded in a slice preparation from the
      spinal cord of neonatal mice. Neurons responded to electrical stimulation by
      monosynaptic EPSCs (excitatory monosynaptic postsynaptic currents). We used mice
      expressing the enhanced green fluorescent protein under the promoter of the glial
      fibrillary acidic protein to identify astrocytes. Chelating calcium with BAPTA in
      a single neighboring astrocyte increased the amplitude of synaptic currents. In
      contrast, when we selectively stimulated astrocytes by activating PAR-1 receptors
      with the peptide TFLLR, the amplitude of EPSCs evoked by a paired stimulation
      protocol was reduced. The paired-pulse ratio was increased, suggesting an
      inhibition occurring at the presynaptic side of synapses. In the presence of
      blockers for extracellular ectonucleotidases, TFLLR did not induce presynaptic
      inhibition. Puffing adenosine reproduced the effect of TFLLR and blocking
      adenosine A1 receptors with 8-Cyclopentyl-1,3-dipropylxanthine prevented it.
      Altogether our results show that ventral horn astrocytes are responsible for a
      tonic and a phasic inhibition of excitatory synaptic transmission by releasing
      ATP, which gets converted into adenosine that binds to inhibitory presynaptic A1
      receptors. 

PMID- 24926237
TI  - Ascending midbrain dopaminergic axons require descending GAD65 axon fascicles for
      normal pathfinding.
AB  - The Nigrostriatal pathway (NSP) is formed by dopaminergic axons that project from
      the ventral midbrain to the dorsolateral striatum as part of the medial forebrain
      bundle. Previous studies have implicated chemotropic proteins in the formation of
      the NSP during development but little is known of the role of substrate-anchored
      signals in this process. We observed in mouse and rat embryos that midbrain
      dopaminergic axons ascend in close apposition to descending GAD65-positive axon
      bundles throughout their trajectory to the striatum. To test whether such
      interaction is important for dopaminergic axon pathfinding, we analyzed
      transgenic mouse embryos in which the GAD65 axon bundle was reduced by the
      conditional expression of the diphtheria toxin. In these embryos we observed
      dopaminergic misprojection into the hypothalamic region and abnormal projection
      in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos
      revealed that the previously described dopaminergic misprojection in these
      embryos is accompanied by severe alterations in the GAD65 axon scaffold.
      Additional studies with cultured dopaminergic neurons and whole embryos suggest
      that NCAM and Robo proteins are involved in the interaction of GAD65 and
      dopaminergic axons. These results indicate that the fasciculation between
      descending GAD65 axon bundles and ascending dopaminergic axons is required for
      the stereotypical NSP formation during brain development and that known guidance
      cues may determine this projection indirectly by instructing the pathfinding of
      the axons that are part of the GAD65 axon scaffold. 

PMID- 24926238
TI  - The mouse olfactory peduncle. 3. Development of neurons, glia, and centrifugal
      afferents.
AB  - The present series of studies was designed to provide a general overview of the
      development of the region connecting the olfactory bulb to the forebrain. The
      olfactory peduncle (OP) contains several structures involved in processing odor
      information with the anterior olfactory nucleus (cortex) being the largest and
      most studied. Results indicate that considerable growth occurs in the peduncle
      from postnatal day (P)10-P20, with reduced expansion from P20 to P30. No evidence
      was found for the addition of new projection or interneurons during the postnatal
      period. GABAergic cells decreased in both number and density after P10. Glial
      populations exhibited different patterns of development, with astrocytes
      declining in density from P10 to P30, and both oligodendrocytes and microglia
      increasing through the interval. Myelination in the anterior commissure emerged
      between P11 and P14. Dense cholinergic innervation was observed at P10 and
      remained relatively stable through P30, while considerable maturation of
      serotonergic innervation occurred through the period. Unilateral naris occlusion
      from P1 to P30 resulted in about a 30% reduction in the size of the ipsilateral
      peduncle but few changes were observed on the contralateral side. The ipsilateral
      peduncle also exhibited higher densities of GAD67-containing interneurons and
      cholinergic fibers suggesting a delay in normal developmental pruning. Lower
      densities of interneurons expressing CCK, somatostatin, and NPY and in myelin
      basic protein staining were also observed. Understanding variations in
      developmental trajectories within the OP may be an important tool for unraveling
      the functions of the region. 

PMID- 24926239
TI  - Vestibular control of entorhinal cortex activity in spatial navigation.
AB  - Navigation in rodents depends on both self-motion (idiothetic) and external
      (allothetic) information. Idiothetic information has a predominant role when
      allothetic information is absent or irrelevant. The vestibular system is a major
      source of idiothetic information in mammals. By integrating the signals generated
      by angular and linear accelerations during exploration, a rat is able to generate
      and update a vector pointing to its starting place and to perform accurate
      return. This navigation strategy, called path integration, has been shown to
      involve a network of brain structures. Among these structures, the entorhinal
      cortex (EC) may play a pivotal role as suggested by lesion and
      electrophysiological data. In particular, it has been recently discovered that
      some neurons in the medial EC display multiple firing fields producing a regular
      grid-like pattern across the environment. Such regular activity may arise from
      the integration of idiothetic information. This hypothesis would be strongly
      strengthened if it was shown that manipulation of vestibular information
      interferes with grid cell activity. In the present paper we review
      neuroanatomical and functional evidence indicating that the vestibular system
      influences the activity of the brain network involved in spatial navigation. We
      also provide new data on the effects of reversible inactivation of the peripheral
      vestibular system on the EC theta rhythm. The main result is that tetrodotoxin
      (TTX) administration abolishes velocity-controlled theta oscillations in the EC,
      indicating that vestibular information is necessary for EC activity. Since recent
      data demonstrate that disruption of theta rhythm in the medial EC induces a
      disorganization of grid cell firing, our findings indicate that the integration
      of idiothetic information in the EC is essential to form a spatial representation
      of the environment. 

PMID- 24926240
TI  - Acute morphine alters GABAergic transmission in the central amygdala during
      naloxone-precipitated morphine withdrawal: role of cyclic AMP.
AB  - The central amygdala (CeA) plays an important role in opioid addiction.
      Therefore, we examined the effects of naloxone-precipitated morphine withdrawal
      (WD) on GABAergic transmission in rat CeA neurons using whole-cell recordings
      with naloxone in the bath. The basal frequency of miniature inhibitory
      postsynaptic currents (mIPSCs) increased in CeA neurons from WD compared to
      placebo rats. Acute morphine (10 MU M) had mixed effects (>=20% change from
      baseline) on mIPSCs in placebo and WD rats. In most CeA neurons (64%) from
      placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In
      32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had
      no effect on mIPSC frequency. In WD rats, acute morphine significantly increased
      mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In
      45% of cells, acute morphine significantly decreased mIPSC frequency and
      amplitude. Pre-treatment with the cyclic AMP inhibitor (R)-adenosine, cyclic
      3',5'-(hydrogenphosphorothioate) triethylammonium (RP), prevented acute morphine
      induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein
      subunit inhibitor pertussis toxin (PTX) did not prevent the acute morphine
      induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC
      frequencies and amplitudes only in WD rats. The results suggest that inhibition
      of GABAergic transmission in the CeA by acute morphine is mediated by PTX
      insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for
      non-morphine responsive cells; by contrast, potentiation of GABAergic
      transmission is mediated by activated cAMP signaling that also mediates the
      increased basal GABAergic transmission in WD rats. Our data indicate that during
      the acute phase of WD, the CeA opioid and GABAergic systems undergo
      neuroadaptative changes conditioned by a previous chronic morphine exposure and
      dependence. 

PMID- 24926241
TI  - Olfactory bulb encoding during learning under anesthesia.
AB  - Neural plasticity changes within the olfactory bulb are important for olfactory
      learning, although how neural encoding changes support new associations with
      specific odors and whether they can be investigated under anesthesia, remain
      unclear. Using the social transmission of food preference olfactory learning
      paradigm in mice in conjunction with in vivo microdialysis sampling we have shown
      firstly that a learned preference for a scented food odor smelled on the breath
      of a demonstrator animal occurs under isofluorane anesthesia. Furthermore,
      subsequent exposure to this cued odor under anesthesia promotes the same pattern
      of increased release of glutamate and gamma-aminobutyric acid (GABA) in the
      olfactory bulb as previously found in conscious animals following olfactory
      learning, and evoked GABA release was positively correlated with the amount of
      scented food eaten. In a second experiment, multiarray (24 electrodes)
      electrophysiological recordings were made from olfactory bulb mitral cells under
      isofluorane anesthesia before, during and after a novel scented food odor was
      paired with carbon disulfide. Results showed significant increases in overall
      firing frequency to the cued-odor during and after learning and decreases in
      response to an uncued odor. Analysis of patterns of changes in individual neurons
      revealed that a substantial proportion (>50%) of them significantly changed their
      response profiles during and after learning with most of those previously
      inhibited becoming excited. A large number of cells exhibiting no response to the
      odors prior to learning were either excited or inhibited afterwards. With the
      uncued odor many previously responsive cells became unresponsive or inhibited.
      Learning associated changes only occurred in the posterior part of the olfactory
      bulb. Thus olfactory learning under anesthesia promotes extensive, but spatially
      distinct, changes in mitral cell networks to both cued and uncued odors as well
      as in evoked glutamate and GABA release. 

PMID- 24926242
TI  - Disrutpted resting-state functional architecture of the brain after 45-day
      simulated microgravity.
AB  - Long-term spaceflight induces both physiological and psychological changes in
      astronauts. To understand the neural mechanisms underlying these physiological
      and psychological changes, it is critical to investigate the effects of
      microgravity on the functional architecture of the brain. In this study, we used
      resting-state functional MRI (rs-fMRI) to study whether the functional
      architecture of the brain is altered after 45 days of -6 degrees  head-down tilt
      (HDT) bed rest, which is a reliable model for the simulation of microgravity.
      Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days
      of -6 degrees  HDT bed rest. Specifically, we used a commonly employed graph
      based measure of network organization, i.e., degree centrality (DC), to perform a
      full-brain exploration of the regions that were influenced by simulated
      microgravity. We subsequently examined the functional connectivities of these
      regions using a seed-based resting-state functional connectivity (RSFC) analysis.
      We found decreased DC in two regions, the left anterior insula (aINS) and the
      anterior part of the middle cingulate cortex (MCC; also called the dorsal
      anterior cingulate cortex in many studies), in the male volunteers after 45 days
      of -6 degrees  HDT bed rest. Furthermore, seed-based RSFC analyses revealed that
      a functional network anchored in the aINS and MCC was particularly influenced by
      simulated microgravity. These results provide evidence that simulated
      microgravity alters the resting-state functional architecture of the brains of
      males and suggest that the processing of salience information, which is primarily
      subserved by the aINS-MCC functional network, is particularly influenced by
      spaceflight. The current findings provide a new perspective for understanding the
      relationships between microgravity, cognitive function, autonomic neural
      function, and central neural activity. 

PMID- 24926243
TI  - Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via
      systematic novelty exposure: the influence of maternal HPA function.
AB  - In the rat, repeated brief exposures to novelty early in life can induce long
      lasting enhancements in adult cognitive, social, emotional, and neuroendocrine
      function. Family-to-family variations in these intervention effects on adult
      offspring are predicted by the mother's ability to mount a rapid corticosterone
      (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we
      investigated whether neonatal and adulthood novelty exposure, each individually
      and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA)
      regulation. Using a 2 * 2 within-litter design, one half of each litter were
      exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily
      during infancy (PND 1-21) and the other half of the litter remained in the home
      cage (Neo_Home); we further exposed half of these two groups to early adulthood
      (PND 54-63) novelty exposure in an open field and the remaining siblings stayed
      in their home cages. Two aspects of HPA regulation were assessed: the ability to
      maintain a low level of resting CORT (CORTB) and the ability to mount a large
      rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of
      adult offspring's ability to regulate HPA regulation began at 370 days of age. We
      further investigated whether the novelty exposure effects on offspring HPA
      regulation are sensitive to the context of maternal HPA regulation by assessing
      maternal HPA regulation similarly beginning 7 days after her pups were weaned. We
      found that at the population level, rats receiving neonatal, but not early
      adulthood exposure or both, showed a greater rapid CORTE than their home-staying
      siblings. At the individual family level, these novelty effects are positively
      associated with maternal CORTE. These results suggest that early experience of
      novelty can enhance the offspring's ability to mount a rapid response to
      environmental challenge and the success of such early life intervention is
      critically dependent upon the context of maternal HPA regulation. 

PMID- 24926244
TI  - The evolution of leader-follower reciprocity: the theory of service-for-prestige.
AB  - We describe the service-for-prestige theory of leadership, which proposes that
      voluntary leader-follower relations evolved in humans via a process of reciprocal
      exchange that generated adaptive benefits for both leaders and followers. We
      propose that although leader-follower relations first emerged in the human
      lineage to solve problems related to information sharing and social coordination,
      they ultimately evolved into exchange relationships whereby followers could
      compensate leaders for services which would otherwise have been prohibitively
      costly for leaders to provide. In this exchange, leaders incur costs to provide
      followers with public goods, and in return, followers incur costs to provide
      leaders with prestige (and associated fitness benefits). Because whole groups of
      followers tend to gain from leader-provided public goods, and because prestige is
      costly for followers to produce, the provisioning of prestige to leaders requires
      solutions to the "free rider" problem of disrespectful followers (who benefit
      from leader services without sharing the costs of producing prestige). Thus
      service-for-prestige makes the unique prediction that disrespectful followers of
      beneficial leaders will be targeted by other followers for punitive sentiment
      and/or social exclusion. Leader-follower relations should be more reciprocal and
      mutually beneficial when leaders and followers have more equal social bargaining
      power. However, as leaders gain more relative power, and their high status
      becomes less dependent on their willingness to pay the costs of benefitting
      followers, service-for-prestige predicts that leader-follower relations will
      become based more on leaders' ability to dominate and exploit rather than benefit
      followers. We review evidential support for a set of predictions made by service
      for-prestige, and discuss how service-for-prestige relates to social neuroscience
      research on leadership. 

PMID- 24926245
TI  - Defining (trained) grapheme-color synesthesia.

PMID- 24926246
TI  - The modern search for the Holy Grail: is neuroscience a solution?
AB  - Neuroscience has become prevalent in recent years; nevertheless, its value in the
      examination of psychological and philosophical phenomena is still a matter of
      debate. The examples reviewed here suggest that neuroscientific tools can be
      significant in the investigation of such complex phenomena. In this article, we
      argue that it is important to study concepts that do not have a clear
      characterization and emphasize the role of neuroscience in this quest for
      knowledge. The data reviewed here suggest that neuroscience may (1) enrich our
      knowledge; (2) outline the nature of an explanation; and (3) lead to substantial
      empirical and theoretical discoveries. To that end, we review work on hedonia and
      eudaimonia in the fields of neuroscience, psychology, and philosophy. These
      studies demonstrate the importance of neuroscientific tools in the investigation
      of phenomena that are difficult to define using other methods. 

PMID- 24926247
TI  - Proprioceptive drift in the rubber hand illusion is intensified following 1 Hz
      TMS of the left EBA.
AB  - The rubber hand illusion (RHI) is a paradigm used to induce an illusory feeling
      of owning a dummy hand through congruent multisensory stimulation. Thus, it can
      grant insights into how our brain represents our body as our own. Recent research
      has demonstrated an involvement of the extrastriate body area (EBA), an area of
      the brain that is typically implicated in the perception of non-face body parts,
      in illusory body ownership. In this experiment, we sought causal evidence for the
      involvement of the EBA in the RHI. Sixteen participants took part in a sham
      controlled, 1 Hz repetitive transcranial magnetic stimulation (rTMS) experiment.
      Participants received (RHI condition) or asynchronous (control) stroking and were
      asked to report the perceived location of their real hand, as well as the
      intensity and the temporal onset of experienced ownership of the dummy hand.
      Following rTMS of the left EBA, participants misjudged their real hand's location
      significantly more toward the dummy hand during the RHI than after sham
      stimulation. This difference in "proprioceptive drift" provides the first causal
      evidence that the EBA is involved in the RHI and subsequently in body
      representation and further supports the view that the EBA is necessary for
      multimodal integration. 

PMID- 24926248
TI  - Rhythm perception and production predict reading abilities in developmental
      dyslexia.
AB  - Rhythm organizes events in time and plays a major role in music, but also in the
      phonology and prosody of a language. Interestingly, children with developmental
      dyslexia-a learning disability that affects reading acquisition despite normal
      intelligence and adequate education-have a poor rhythmic perception. It has been
      suggested that an accurate perception of rhythmical/metrical structure, that
      requires accurate perception of rise time, may be critical for phonological
      development and subsequent literacy. This hypothesis is mostly based on results
      showing a high degree of correlation between phonological awareness and metrical
      skills, using a very specific metrical task. We present new findings from the
      analysis of a sample of 48 children with a diagnosis of dyslexia, without
      comorbidities. These children were assessed with neuropsychological tests, as
      well as specifically-devised psychoacoustic and musical tasks mostly testing
      temporal abilities. Associations were tested by multivariate analyses including
      data mining strategies, correlations and most importantly logistic regressions to
      understand to what extent the different auditory and musical skills can be a
      robust predictor of reading and phonological skills. Results show a strong link
      between several temporal skills and phonological and reading abilities. These
      findings are discussed in the framework of the neuroscience literature comparing
      music and language processing, with a particular interest in the links between
      rhythm processing in music and language. 

PMID- 24926249
TI  - Amygdala activation during emotional face processing in adolescents with
      affective disorders: the role of underlying depression and anxiety symptoms.
AB  - Depressive and anxiety disorders are often first diagnosed during adolescence and
      it is known that they persist into adulthood. Previous studies often tried to
      dissociate depressive and anxiety disorders, but high comorbidity makes this
      difficult and maybe even impossible. The goal of this study was to use
      neuroimaging to test what the unique contribution is of depression and anxiety
      symptomatology on emotional processing and amygdala activation, and to compare
      the results with a healthy control group. We included 25 adolescents with
      depressive and/or anxiety disorders and 26 healthy adolescents. Participants
      performed an emotional face processing task while in the MRI scanner. We were
      particularly interested in the relation between depression/anxiety symptomatology
      and patterns of amygdala activation. There were no significant differences in
      activation patterns between the control group and the clinical group on whole
      brain level and ROI level. However, we found that dimensional scores on an
      anxiety but not a depression subscale significantly predicted brain activation in
      the right amygdala when processing fearful, happy and neutral faces. These
      results suggest that anxiety symptoms are a better predictor for differentiating
      activation patterns in the amygdala than depression symptoms. Although the
      current study includes a relatively large sample of treatment naive adolescents
      with depression/anxiety disorders, results might be influenced by differences
      between studies in recruitment strategies or methodology. Future research should
      include larger samples with a more equal distribution of adolescents with a
      clinical diagnosis of depression and/or anxiety. To conclude, this study shows
      that abnormal amygdala responses to emotional faces in depression and anxiety
      seems to be more dependent on anxiety symptoms than on depression symptoms, and
      thereby highlights the need for more research to better characterize clinical
      groups in future studies. 

PMID- 24926250
TI  - Do we need a theory-based assessment of consciousness in the field of disorders
      of consciousness?

PMID- 24926251
TI  - Beyond inhibition: a dual-process perspective to renew the exploration of binge
      drinking.
AB  - Binge drinking is a widespread alcohol-consumption pattern in youth and is linked
      to cognitive consequences, mostly for executive functions. However, other crucial
      factors remain less explored in binge drinking and notably the emotional
      automatic processes. Dual-process model postulates that addictive disorders are
      not only due to impaired reflective system (involved in deliberate behaviors),
      but rather to an imbalance between under-activated reflective system and over
      activated affective-automatic one (involved in impulsive behaviors). This
      proposal has been confirmed in alcohol-dependence, but has not been tested in
      binge drinking. The observation of comparable impairments in binge drinking and
      alcohol-dependence led to the "continuum hypothesis," suggesting similar deficits
      across different alcohol-related disorders. In this perspective, applying the
      dual-process model to binge drinking might renew the understanding of this
      continuum hypothesis. A three-axes research agenda will be proposed, exploring:
      (1) the affective-automatic system in binge drinking; (2) the systems'
      interactions and imbalance in binge drinking; (3) the evolution of this imbalance
      in the transition between binge drinking and alcohol-dependence. 

PMID- 24926252
TI  - Automated collection of imaging and phenotypic data to centralized and
      distributed data repositories.
AB  - Accurate data collection at the ground level is vital to the integrity of
      neuroimaging research. Similarly important is the ability to connect and curate
      data in order to make it meaningful and sharable with other investigators.
      Collecting data, especially with several different modalities, can be time
      consuming and expensive. These issues have driven the development of automated
      collection of neuroimaging and clinical assessment data within COINS
      (Collaborative Informatics and Neuroimaging Suite). COINS is an end-to-end data
      management system. It provides a comprehensive platform for data collection,
      management, secure storage, and flexible data retrieval (Bockholt et al., 2010;
      Scott et al., 2011). It was initially developed for the investigators at the Mind
      Research Network (MRN), but is now available to neuroimaging institutions
      worldwide. Self Assessment (SA) is an application embedded in the Assessment
      Manager (ASMT) tool in COINS. It is an innovative tool that allows participants
      to fill out assessments via the web-based Participant Portal. It eliminates the
      need for paper collection and data entry by allowing participants to submit their
      assessments directly to COINS. Instruments (surveys) are created through ASMT and
      include many unique question types and associated SA features that can be
      implemented to help the flow of assessment administration. SA provides an
      instrument queuing system with an easy-to-use drag and drop interface for
      research staff to set up participants' queues. After a queue has been created for
      the participant, they can access the Participant Portal via the internet to fill
      out their assessments. This allows them the flexibility to participate from home,
      a library, on site, etc. The collected data is stored in a PostgresSQL database
      at MRN. This data is only accessible by users that have explicit permission to
      access the data through their COINS user accounts and access to MRN network. This
      allows for high volume data collection and with minimal user access to PHI
      (protected health information). An added benefit to using COINS is the ability to
      collect, store and share imaging data and assessment data with no interaction
      with outside tools or programs. All study data collected (imaging and assessment)
      is stored and exported with a participant's unique subject identifier so there is
      no need to keep extra spreadsheets or databases to link and keep track of the
      data. Data is easily exported from COINS via the Query Builder and study portal
      tools, which allow fine grained selection of data to be exported into comma
      separated value file format for easy import into statistical programs. There is a
      great need for data collection tools that limit human intervention and error
      while at the same time providing users with intuitive design. COINS aims to be a
      leader in database solutions for research studies collecting data from several
      different modalities. 

PMID- 24926253
TI  - Solar elastosis in its papular form: uncommon, mistakable.
AB  - Solar elastosis is a degenerative condition of elastic tissue in the dermis due
      to prolonged sun exposure. There are a variety of clinical manifestations of
      solar elastosis. In its most common form, solar elastosis manifests as yellow,
      thickened, coarsely wrinkled skin. We report two uncommon cases of severe solar
      elastosis with a papular morphology. Its presentation can closely mimic a host of
      cutaneous disorders and thus, although it is helpful to be cognizant of this
      entity, it is still crucial to biopsy these lesions to avoid missing a more
      sinister condition. 

PMID- 24926254
TI  - Bullous mastocytosis mimicking congenital epidermolysis bullosa.
AB  - A 2-month-old female infant was referred to DebRA Mexico from the Regional
      Children's Hospital because of a generalized dermatosis from birth characterized
      by multiple blisters and erosions on the trunk, face and limbs, associated with
      minor trauma. A skin biopsy showing subepidermal blisters associated with a
      dermal infiltrate of Giemsa-positive cells and CD117-positive antibody was
      consistent with the diagnosis of bullous mastocytosis. Treatment with oral
      antihistamines, topical steroids, and antibiotics was initiated, leading to a
      remission of the lesions. 

PMID- 24926255
TI  - Dermatofibrosarcoma protuberans: a case report.
AB  - We present a typical case of dermatofibrosarcoma protuberans with local
      recurrence 2 months after surgery and, motivated by this patient, make a review
      of the most important aspects. This is a rare tumor and we call special attention
      to the fact that its recurrence is extremely frequent, so there is absolute need
      to observe these patients periodically after surgery. 

PMID- 24926256
TI  - Fatal interstitial lung disease after addition of sorafenib to a patient with
      lung adenocarcinoma who had failed to improve with erlotinib alone.
AB  - Interstitial lung disease (ILD) induced by epidermal growth factor receptor
      tyrosine kinase inhibitors has been extensively documented with decreasing
      incidence after appropriate patient selection due to increasing awareness over
      the years. However, ILD induced by sorafenib was mentioned with lower frequency
      only in patients with hepatocellular and renal cell carcinoma living in Japan but
      not in patients with other carcinomas or living outside Japan, and it has been
      overlooked in clinical practice. In the present case, sorafenib was added to the
      treatment of a 60-year-old non-smoking patient with non-small cell lung cancer
      (NSCLC). After his failing to improve with erlotinib alone, erlotinib was
      continued to be given in combination with sorafenib as a salvage therapy.
      Although clinical signs of ILD were observed 2 weeks after the addition of
      sorafenib, the radiological diagnosis of ILD was only made 41 days after the
      initiation of the combination treatment, and the patient died 56 days after
      treatment onset. It was concluded that ILD was indeed induced by sorafenib. This
      is the first report of ILD induced by sorafenib in a patient with NSCLC living
      outside Japan. Oncologists should be aware of this fatal complication for its
      early detection in order to avoid a severe course of ILD leading to a decrease in
      the ILD mortality rate. 

PMID- 24926257
TI  - Long-Term Response in a Patient with del(5q) Myelodysplastic Syndrome Who
      Discontinued Lenalidomide and Obtained a Good Response and Tolerance to
      Rechallenge.
AB  - BACKGROUND: The introduction of the immunomodulatory drug lenalidomide has
      revolutionized the treatment of patients with myelodysplastic syndromes (MDS) and
      deletion of the long arm of chromosome 5. Treatment with lenalidomide results in
      transfusion independence in the majority of patients, but some questions remain
      unresolved, among them the duration of treatment. Moreover, a number of
      unexpected long-term remissions in patients who stopped lenalidomide for various
      reasons have been observed. CASE REPORT: We report the case of a 60-year-old
      Caucasian male with deletion of the long arm of chromosome 5 and International
      Prognostic Scoring System (IPSS)-defined low-risk MDS who was treated with
      lenalidomide, achieving complete cytogenetic remission and erythroid response.
      After tapering off and interrupting the treatment, the patient relapsed and
      showed a new response by lenalidomide retreatment. Six years after the initial
      treatment, we registered a durable erythroid long-term response and good
      tolerance, but there was no evidence of a very profound cytogenetic response
      compared to using lenalidomide as a first-line treatment. Cytogenetic and
      fluorescence in situ hybridization together with hemoglobin level, mean
      corpuscular volume (MCV) and vitamin B12 level helped us to monitor the patient
      response; during the various phases of lenalidomide treatment, MCV and vitamin
      B12 normalization correlated with good response. CONCLUSION: Lenalidomide
      interruption and rechallenge in some 5q- MDS patients, with low risk according to
      the IPSS, is safe and feasible but does not result in a profound cytogenetic
      response.

PMID- 24926258
TI  - Bazex syndrome revealing a gastric cancer.
AB  - We herein report the case of a 73-year-old woman who developed skin and nail
      disorders 2 months before her digestive symptoms started, which lead to the
      diagnosis of gastric adenocarcinoma. The lesions were diagnosed as Bazex
      syndrome, usually seen in squamous cell carcinoma. Under systemic chemotherapy,
      the cutaneous signs improved for some months before worsening when the disease
      progressed. 

PMID- 24926259
TI  - Occurrence and Recurrence of Hepatocellular Carcinoma Were Not Rare Events during
      Phlebotomy in Older Hepatitis C Virus-Infected Patients.
AB  - The use of phlebotomy is relatively common for 'difficult-to-treat by antiviral
      therapies' hepatitis C virus (HCV)-infected patients and for certain patients
      having chronic liver diseases with an iron overload of the liver. In the present
      study, we retrospectively analyzed patients treated with phlebotomy and their
      adverse events. We observed the occurrence and recurrence of hepatocellular
      carcinoma, and the appearance of ascites in some patients infected with HCV as
      well as the reduction of serum ferritin and alanine aminotransferase levels.
      Severe adverse events necessitating a cessation of phlebotomy occurred
      independently of alpha-fetoprotein (>10 ng/ml) in patients infected with HCV
      according to multivariate logistic regression analysis. These findings may serve
      as a basis for phlebotomy especially in older patients with chronic hepatitis C. 

PMID- 24926260
TI  - Malignant Melanoma with Concurrent BRAF E586K and NRAS Q81K Mutations.
AB  - Cutaneous melanoma is an aggressive malignant tumor of melanocytes which accounts
      for 80% of skin cancer-related deaths. A number of driver mutations have been
      identified in melanoma, with the mutually exclusive BRAF V600E and NRAS Q61A
      mutations together accounting for roughly 70% of mutations. Simultaneous BRAF
      V600E and NRAS Q61A mutations in melanoma are rare, with evidence suggesting that
      up to 2.9% (2/69) of primary cutaneous melanomas carry both mutations. Here we
      describe a 42-year-old man with concurrent BRAF E586K and NRAS Q81K driver
      mutations. To our knowledge, this is the first description of these driver
      mutations occurring simultaneously in primary cutaneous melanoma. 

PMID- 24926261
TI  - A case of dural arteriovenous fistula presenting as acute subdural hematoma.
AB  - Dural arteriovenous fistula (AVF) presenting with subdural hematoma is relatively
      rare. We report a case of dural AVF presenting as acute subdural hematoma (ASDH)
      and provide a review of the literature. A 56-year-old man presented with
      disturbance of consciousness. Computed tomography demonstrated a right ASDH and a
      small right occipital subcortical hematoma. Cerebral angiography showed a dural
      AVF on the occipital convexity draining into the cortical veins. Emergent
      endovascular embolization was immediately performed and the shunt flow
      disappeared. Hematoma removal and external decompression were safely conducted.
      Combined therapy successfully recovered the patient's consciousness level. This
      rare case of dural AVF presenting with ASDH was treated with combined treatments
      of endovascular and open surgery. 

PMID- 24926262
TI  - Vocalization in dementia: a case report and review of the literature.
AB  - BACKGROUND: Vocalizations are part of the spectrum of the 'negative' behavioral
      and psychological symptoms of dementia (BPSD). We describe a patient with
      moderate-stage mixed dementia of Alzheimer's disease and cerebrovascular disease
      and a left orbitofrontal lesion exhibiting vocalization. The use of 'redirection'
      has been demonstrated to be an effective nonpharmacological means of controlling
      BPSD, while reducing caregiver distress. CASE REPORT: A 78-year-old right-handed
      African-American female presented with complaints of worsening memory and BPSD,
      causing significant caregiver distress. Throughout the evaluation, she constantly
      vocalized her son's name and made a continuous grunting noise, correlating with
      increased anxiety/agitation. We utilized a redirection technique, which achieved
      the immediate reduction of the vocalization symptoms. Caregiver psychoeducation
      was provided allowing them to use the redirection technique at home. CONCLUSIONS:
      In patients with dementia exhibiting negative symptoms of BPSD, using
      nonpharmacologic techniques (i.e. redirection) may be indicated. Psychotropic
      medications rarely address negative BPSD symptoms, while simultaneously
      decreasing patient's quality of life. Nonpharmacologic approaches are beneficial
      as first-line therapy for negative BPSD.

PMID- 24926263
TI  - Combined ipsilateral oculomotor nerve palsy and contralateral downbeat nystagmus
      in a case of cerebral infarction.
AB  - We report a patient with acute cerebral infarction of the left paramedian
      thalamus, upper mesencephalon and cerebellum who exhibited ipsilateral oculomotor
      nerve palsy and contralateral downbeat nystagmus. The site of the infarction was
      considered to be the paramedian thalamopeduncular and cerebellar regions, which
      are supplied by the superior cerebellar artery containing direct perforating
      branches or both the superior cerebellar artery and the superior mesencephalic
      and posterior thalamosubthalamic arteries. Contralateral and monocular downbeat
      nystagmus is very rare. Our case suggests that the present downbeat nystagmus was
      due to dysfunction of cerebellar-modulated crossed oculovestibular fibers of the
      superior cerebellar peduncle or bilateral downbeat nystagmus with one-sided
      oculomotor nerve palsy. 

PMID- 24926264
TI  - Sudden coma from acute bilateral m1 occlusion: successful treatment with
      mechanical thrombectomy.
AB  - We report a case with acute small infarct of the left middle cerebral artery in a
      72-year-old man with atrial fibrillation documented by MRI and MR angiography.
      One hour later, he lost consciousness and CT with CT angiography revealed
      bilateral hyperdense middle cerebral arteries due to occlusion of the M1
      segments. Mechanical thrombectomy of the right middle cerebral artery was
      successfully performed. During that time, thrombosis on the left side had
      progressed to carotid T occlusion, which was recanalized as well. The patient had
      a good outcome with slight aphasia and mild paresis of the left hand and could be
      transferred to rehabilitation 2 weeks later. 

PMID- 24926265
TI  - A rare case of Parkinson's disease with severe neck pain owing to crowned dens
      syndrome.
AB  - BACKGROUND: Pain is regarded as one of the most common nonmotor symptoms in
      Parkinson's disease (PD). In particular, musculoskeletal pain has been reported
      as the most common type of PD-associated pain. Crowned dens syndrome (CDS),
      related to microcrystalline deposition in the periodontoid process, is the main
      cause of acute or chronic cervical pain. CASE PRESENTATION: This report describes
      the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity,
      gait disturbance and neck pain. Laboratory examination revealed marked elevations
      of white blood cells (10,100/ul) and C-reactive protein (CRP; 8.63 mg/dl). She
      was primarily diagnosed with severe and untreated PD, corresponding to Hoehn and
      Yahr scale score IV, with musculoskeletal pain and urinary tract infection. The
      patient was treated with antiparkinsonism drugs, antibiotic agents and
      nonsteroidal anti-inflammatory drugs, but they had only limited effects. Cervical
      plain computed tomography (CT) scanning detected remarkable crown-like
      calcification surrounding the odontoid process. Based on CT findings, the patient
      was diagnosed as having CDS with PD, and was immediately treated with
      corticosteroid. The severe neck rigidity with pain and the serum CRP level (0.83
      mg/dl) of the patient were drastically improved within a week by the additional
      corticosteroid therapy. CONCLUSION: Severe neck rigidity and bradykinesia in this
      patient might have strengthened the chondrocalcinosis around the odontoid
      process. Cervical plain CT scan is necessary and useful for the definitive
      diagnosis of CDS. CDS should be considered as a differential diagnosis of a
      possible etiology for musculoskeletal pain related to rigidity and bradykinesia
      in PD.

PMID- 24926266
TI  - Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia
      gravis.
AB  - INTRODUCTION: Progressive outer retinal necrosis (PORN) is a rare but devastating
      infectious retinitis associated with varicella zoster virus (VZV) and responsible
      for severe visual loss. CASE REPORT: A 59-year-old man treated for generalized
      myasthenia with oral azathioprine and prednisone presented with severe unilateral
      necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous
      humors was diagnostic for VZV PORN. CONCLUSION: VZV PORN is a severe potential
      ocular complication of immunosuppression, prompting urgent diagnosis and
      appropriate treatment.

PMID- 24926267
TI  - Like iron in the blood of the people: the requirement for heme trafficking in
      iron metabolism.
AB  - Heme is an iron-containing porphyrin ring that serves as a prosthetic group in
      proteins that function in diverse metabolic pathways. Heme is also a major source
      of bioavailable iron in the human diet. While the synthesis of heme has been well
      characterized, the pathways for heme trafficking remain poorly understood. It is
      likely that heme transport across membranes is highly regulated, as free heme is
      toxic to cells. This review outlines the requirement for heme delivery to various
      subcellular compartments as well as possible mechanisms for the mobilization of
      heme to these compartments. We also discuss how these trafficking pathways might
      function during physiological events involving inter- and intra-cellular
      mobilization of heme, including erythropoiesis, erythrophagocytosis, heme
      absorption in the gut, as well as heme transport pathways supporting embryonic
      development. Lastly, we aim to question the current dogma that heme, in toto, is
      not mobilized from one cell or tissue to another, outlining the evidence for
      these pathways and drawing parallels to other well-accepted paradigms for copper,
      iron, and cholesterol homeostasis. 

PMID- 24926268
TI  - Iron, hepcidin, and the metal connection.
AB  - Identification of new players in iron metabolism, such as hepcidin, which
      regulates ferroportin and divalent metal transporter 1 expression, has improved
      our knowledge of iron metabolism and iron-related diseases. However, from both
      experimental data and clinical findings, "iron-related proteins" appear to also
      be involved in the metabolism of other metals, especially divalent cations.
      Reports have demonstrated that some metals may affect, directly or indirectly,
      the expression of proteins involved in iron metabolism. Throughout their lives,
      individuals are exposed to various metals during personal and/or occupational
      activities. Therefore, better knowledge of the connections between iron and other
      metals could improve our understanding of iron-related diseases, especially the
      variability in phenotypic expression, as well as a variety of diseases in which
      iron metabolism is secondarily affected. Controlling the metabolism of other
      metals could represent a promising innovative therapeutic approach. 

PMID- 24926269
TI  - Analysis of homeobox gene action may reveal novel angiogenic pathways in normal
      placental vasculature and in clinical pregnancy disorders associated with
      abnormal placental angiogenesis.
AB  - Homeobox genes are essential for both the development of the blood and lymphatic
      vascular systems, as well as for their maintenance in the adult. Homeobox genes
      comprise an important family of transcription factors, which are characterized by
      a well conserved DNA binding motif; the homeodomain. The specificity of the
      homeodomain allows the transcription factor to bind to the promoter regions of
      batteries of target genes and thereby regulates their expression. Target genes
      identified for homeodomain proteins have been shown to control fundamental cell
      processes such as proliferation, differentiation, and apoptosis. We and others
      have reported that homeobox genes are expressed in the placental vasculature, but
      our knowledge of their downstream target genes is limited. This review highlights
      the importance of studying the cellular and molecular mechanisms by which
      homeobox genes and their downstream targets may regulate important vascular
      cellular processes such as proliferation, migration, and endothelial tube
      formation, which are essential for placental vasculogenesis and angiogenesis. A
      better understanding of the molecular targets of homeobox genes may lead to new
      therapies for aberrant angiogenesis associated with clinically important
      pregnancy pathologies, including fetal growth restriction and preeclampsia. 

PMID- 24926270
TI  - Impaired adenosine-mediated angiogenesis in preeclampsia: potential implications
      for fetal programming.
AB  - Preeclampsia is a pregnancy-specific syndrome, defined by such clinical hallmarks
      as the onset of maternal hypertension and proteinuria after 20 weeks of
      gestation. The syndrome is also characterized by impaired blood flow through the
      utero-placental circulation and relative placental ischemia, which in turn, may
      generate feto-placental endothelial dysfunction. Endothelial dysfunction in
      offspring born from preeclamptic pregnancies has been associated with an
      increased risk of cardiovascular disease, including hypertension, later in life.
      Interestingly, diminished endothelial function, manifested by low angiogenic
      capacity, leads to hypertension in animal studies. Recently, we have shown that
      the adenosine receptor A2A/nitric oxide/vascular endothelial growth factor axis
      is reduced in human umbilical vein endothelial cells derived from preeclamptic
      pregnancies, an effect correlated with gestational age at onset of preeclampsia.
      We and others suggested that impaired vascular function might be associated with
      high cardiovascular risk in offspring exposed to pregnancy diseases. However, we
      are not aware of any studies that examine impaired adenosine-mediated
      angiogenesis as a possible link to hypertension in offspring born from
      preeclamptic pregnancies. In this review, we present evidence supporting the
      hypothesis that reduced adenosine-mediated angiogenesis during preeclamptic
      pregnancies might be associated with development of hypertension in the
      offspring. 

PMID- 24926272
TI  - How intent to interact can affect action scaling of distance: reply to Wilson.

PMID- 24926271
TI  - A distributed effects perspective of dimensionally defined psychiatric disorders:
      and convergent versus core deficit effects in ADHD.
AB  - The focus of psychiatric and psychological research has arguably shifted from
      brain damage and psychosis to more common forms of psychopathology that reflect
      extremes variants of otherwise normal cognitive and behavioral characteristics.
      Now, in addition to trying to understand overtly damaged brain-function (flat
      tire effects), we are also seeking to understand liabilities associated with non
      optimized, but otherwise intact, cognitive and behavioral abilities (poor tuning
      effects). This shift has pushed us to evolve our investigational strategies to
      more broadly consider whole-brain integrated brain systems, as well as seek to
      develop more specific quantifiable indicators of impoverished brain function and
      behavior. This paper discusses such challenges in relation to dimensionally
      defined psychiatric disorders and presents a novel whole-brain integrated
      perspective of ADHD brain function pathology. 

PMID- 24926273
TI  - MEG evidence for conceptual combination but not numeral quantification in the
      left anterior temporal lobe during language production.
AB  - The left anterior temporal lobe (LATL) has risen as a leading candidate for a
      brain locus of composition in language; yet the computational details of its
      function are unknown. Although most literature discusses it as a combinatory
      region in very general terms, it has also been proposed to reflect the more
      specific function of conceptual combination, which in the classic use of this
      term mainly pertains to the combination of open class words with obvious
      conceptual contributions. We aimed to distinguish between these two possibilities
      by contrasting plural nouns in contexts where they were either preceded by a
      color modifier ("red cups"), eliciting conceptual combination, or by a number
      word ("two cups"), eliciting numeral quantification but no conceptual
      combination. This contrast was chosen because within a production task, it allows
      the manipulation of composition type while keeping the physical stimulus
      constant: a display of two red cups can be named as "two cups" or "red cups"
      depending on the task instruction. These utterances were compared to productions
      of two-word number and color lists, intended as non-combinatory control
      conditions. Magnetoencephalography activity was recorded during the planning for
      production, prior to motion artifacts. As expected on the basis of comprehension
      studies, color modification elicited increased LATL activity as compared to color
      lists, demonstrating that this basic combinatory effect is strongly crossmodal.
      However, numeral quantification did not elicit a parallel effect, suggesting that
      the function of the LATL is (i) semantic and not syntactic (given that both color
      modification and numeral quantification involve syntactic composition) and (ii)
      corresponds more closely to the classical psychological notion of conceptual
      combination as opposed to a more general semantic combinatory function. 

PMID- 24926274
TI  - Gated auditory speech perception: effects of listening conditions and cognitive
      capacity.
AB  - This study aimed to measure the initial portion of signal required for the
      correct identification of auditory speech stimuli (or isolation points, IPs) in
      silence and noise, and to investigate the relationships between auditory and
      cognitive functions in silence and noise. Twenty-one university students were
      presented with auditory stimuli in a gating paradigm for the identification of
      consonants, words, and final words in highly predictable and low predictable
      sentences. The Hearing in Noise Test (HINT), the reading span test, and the Paced
      Auditory Serial Attention Test were also administered to measure speech-in-noise
      ability, working memory and attentional capacities of the participants,
      respectively. The results showed that noise delayed the identification of
      consonants, words, and final words in highly predictable and low predictable
      sentences. HINT performance correlated with working memory and attentional
      capacities. In the noise condition, there were correlations between HINT
      performance, cognitive task performance, and the IPs of consonants and words. In
      the silent condition, there were no correlations between auditory and cognitive
      tasks. In conclusion, a combination of hearing-in-noise ability, working memory
      capacity, and attention capacity is needed for the early identification of
      consonants and words in noise. 

PMID- 24926275
TI  - Conscious and unconscious context-specific cognitive control.
AB  - A key feature of the human cognitive system is its ability to deal with an ever
      changing environment. One prototypical example is the observation that we adjust
      our information processing depending on the conflict-likelihood of a context
      (context-specific proportion congruency effect, CSPC, Crump etal., 2006).
      Recently, empirical studies started to question the role of consciousness in
      these strategic adaptation processes (for reviews, see Desender and Van den
      Bussche, 2012; Kunde etal., 2012). However, these studies have not yielded
      unequivocal results (e.g., Kunde, 2003; Heinemann etal., 2009; Van Gaal etal.,
      2010a; Desender etal., 2013; Reuss etal., 2014). In the present study, we aim at
      replicating the experiment of Heinemann etal. (2009) in which the proportion of
      congruent and incongruent trials between different contexts was varied in a
      masked priming task. Their results showed a reduction of the congruency effect
      for the context with more incongruent trials. However, this CSPC effect was only
      observed when the prime-target conflict was conscious, rather than unconscious,
      suggesting that context-specific control operates within the boundaries of
      awareness. Our replication attempt however contrasts these findings. In the first
      experiment we found no evidence for a CSPC effect in reaction times (RTs),
      neither in the conscious nor in the unconscious condition. The error rate
      analysis did show a CSPC effect, albeit not one modulated by consciousness. In
      the second experiment we found an overall CSPC effect in RTs, independent of
      consciousness. The error rates did not display a CSPC pattern. These mixed
      results seem to nuance the findings of Heinemann etal. (2009) and highlight the
      need for replication studies in psychology research. 

PMID- 24926276
TI  - Exploring story grammar structure in the book reading interactions of African
      American mothers and their preschool children: a pilot investigation.
AB  - The aim of this investigation was to identify the book reading behaviors and book
      reading styles of middle class African American mothers engaged in a shared book
      reading activity with their preschool children. To this end, the mothers and
      their children were videotaped reading one of three books, Julius, Grandfather
      and I, or Somewhere in Africa. Both maternal and child behaviors were coded for
      the frequency of occurrence of story grammar elements contained in their stories
      and maternal behaviors were also coded for their use of narrative eliciting
      strategies. In addition, mothers were queried about the quality and quantity of
      book reading/story telling interactions in the home environment. The results
      suggest that there is a great deal of individual variation in how mothers use the
      story grammar elements and narrative eliciting strategies to engage their
      children in a shared book reading activity. Findings are discussed in terms of
      suggestions for additional research and practical applications are offered on
      ways to optimally engage African American preschool children and African American
      families from diverse socioeconomic backgrounds in shared book reading
      interactions. 

PMID- 24926277
TI  - Double threshold in bi- and multilingual contexts: preconditions for higher
      academic attainment in English as an additional language.
AB  - Bi- and multilingualism has been shown to have positive effects on the attainment
      of third and additional languages. These effects, however, depend on the type of
      bi- and multilingualism and the status of the languages involved (Cenoz, 2003;
      Jessner, 2006). In this exploratory trend study, we revisit Cummins' Threshold
      Hypothesis (1979), claiming that bilingual children must reach certain levels of
      attainment in order to (a) avoid academic deficits and (b) allow bilingualism to
      have a positive effect on their cognitive development and academic attainment. To
      this end, we examine the attainment of English as an academic language of 16
      years-old school children from Hamburg (n = 52). Our findings support the
      existence of thresholds for literacy attainment. We argue that language external
      factors may override positive effects of bilingualism. In addition, these factors
      may compensate negative effects attributable to low literacy attainment in German
      and the heritage languages. We also show that low attainment levels in migrant
      children's heritage languages preempt high literacy attainment in additional
      languages. 

PMID- 24926278
TI  - The effect of a career choice guidance on self-reported psychological problems.
AB  - Late adolescents with career choice problems often have psychological problems as
      well. The starting point of this study was the question of career choice
      counselors whether potential clients with career choice problems and
      psychological problems could be accepted in career choice intervention, or
      whether it was better to advise them to seek help for their psychological
      problems. We investigated whether a successful career choice intervention reduced
      psychological problems, and whether this program was equally effective in
      participants with low and with high levels of psychological problems.
      Participants were 45 Dutch students (age 17-24) with career choice problems. They
      had above average levels of self-reported psychological problems before the start
      of the intervention. These problems decreased significantly following the
      intervention. With regard to vocational commitment development, the intervention
      was equally effective for participants with low or average and with (very) high
      levels of psychological problems before the start of the intervention. 

PMID- 24926279
TI  - Evaluating visual and auditory contributions to the cognitive restoration effect.
AB  - It has been suggested that certain real-world environments can have a restorative
      effect on an individual, as expressed in changes in cognitive performance and
      mood. Much of this research builds on Attention Restoration Theory (ART), which
      suggests that environments that have certain characteristics induce cognitive
      restoration via variations in attentional demands. Specifically, natural
      environments that require little top-down processing have a positive effect on
      cognitive performance, while city-like environments show no effect. We
      characterized the cognitive restoration effect further by examining (1) whether
      natural visual stimuli, such as blue spaces, were more likely to provide a
      restorative effect over urban visual stimuli, (2) if increasing immersion with
      environment-related sound produces a similar or superior effect, (3) if this
      effect extends to other cognitive tasks, such as the functional field of view
      (FFOV), and (4) if we could better understand this effect by providing controls
      beyond previous works. We had 202 participants complete a cognitive task battery,
      consisting of a reverse digit span task, the attention network task, and the FFOV
      task prior to and immediately after a restoration period. In the restoration
      period, participants were assigned to one of seven conditions in which they
      listened to natural or urban sounds, watched images of natural or urban
      environments, or a combination of both. Additionally, some participants were in a
      control group with exposure to neither picture nor sound. While we found some
      indication of practice effects, there were no differential effects of restoration
      observed in any of our cognitive tasks, regardless of condition. We did, however,
      find evidence that our nature images and sounds were more relaxing than their
      urban counterparts. Overall, our findings suggest that acute exposure to relaxing
      pictorial and auditory stimulus is insufficient to induce improvements in
      cognitive performance. 

PMID- 24926280
TI  - Implicit learning modulates attention capture: evidence from an item-specific
      proportion congruency manipulation.
AB  - A host of research has now shown that our explicit goals and intentions can, in
      large part, overcome the capture of visual attention by objects that differ from
      their surroundings in terms of size, shape, or color. Surprisingly however, there
      is little evidence for the role of implicit learning in mitigating capture
      effects despite the fact that such learning has been shown to strongly affect
      behavior in a host of other performance domains. Here, we employ a modified
      attention capture paradigm, based on the work of Theeuwes (1991, 1992), in which
      participants must search for an odd-shaped target amongst homogeneous
      distracters. On each trial, there is also a salient, but irrelevant odd-colored
      distracter. Across the experiments reported, we intermix two search contexts: for
      one set of distracters (e.g., squares) the shape singleton and color singleton
      coincide on a majority of trials (high proportion congruent condition), whereas
      for the other set of distracters (e.g., circles) the shape and color singletons
      are highly unlikely to coincide (low proportion congruent condition). Crucially,
      we find that observers learn to allow the capture of attention by the salient
      distracter to a greater extent in the high, compared to the low proportion
      congruent condition, albeit only when search is sufficiently difficult. Moreover,
      this effect of prior experience on search behavior occurs in the absence of
      awareness of our proportion manipulation. We argue that low-level properties of
      the search displays recruit representations of prior experience in a rapid,
      flexible, and implicit manner. 

PMID- 24926281
TI  - French-speaking children's freely produced labels for facial expressions.
AB  - In this study, we investigated the labeling of facial expressions in French
      speaking children. The participants were 137 French-speaking children, between
      the ages of 5 and 11 years, recruited from three elementary schools in Ottawa,
      Ontario, Canada. The facial expressions included expressions of happiness,
      sadness, fear, surprise, anger, and disgust. Participants were shown one facial
      expression at a time, and asked to say what the stimulus person was feeling.
      Participants' responses were coded by two raters who made judgments concerning
      the specific emotion category in which the responses belonged. 5- and 6-year-olds
      were quite accurate in labeling facial expressions of happiness, anger, and
      sadness but far less accurate for facial expressions of fear, surprise, and
      disgust. An improvement in accuracy as a function of age was found for fear and
      surprise only. Labeling facial expressions of disgust proved to be very difficult
      for the children, even for the 11-year-olds. In order to examine the fit between
      the model proposed by Widen and Russell (2003) and our data, we looked at the
      number of participants who had the predicted response patterns. Overall, 88.52%
      of the participants did. Most of the participants used between 3 and 5 labels,
      with correspondence percentages varying between 80.00% and 100.00%. Our results
      suggest that the model proposed by Widen and Russell (2003) is not limited to
      English-speaking children, but also accounts for the sequence of emotion labeling
      in French-Canadian children. 

PMID- 24926282
TI  - Group work as an incentive for learning - students' experiences of group work.
AB  - Group work is used as a means for learning at all levels in educational systems.
      There is strong scientific support for the benefits of having students learning
      and working in groups. Nevertheless, studies about what occurs in groups during
      group work and which factors actually influence the students' ability to learn is
      still lacking. Similarly, the question of why some group work is successful and
      other group work results in the opposite is still unsolved. The aim of this
      article is to add to the current level of knowledge and understandings regarding
      the essence behind successful group work in higher education. This research is
      focused on the students' experiences of group work and learning in groups, which
      is an almost non-existing aspect of research on group work prior to the beginning
      of the 21st century. A primary aim is to give university students a voice in the
      matter by elucidating the students' positive and negative points of view and how
      the students assess learning when working in groups. Furthermore, the students'
      explanations of why some group work ends up being a positive experience resulting
      in successful learning, while in other cases, the result is the reverse, are of
      interest. Data were collected through a study-specific questionnaire, with
      multiple choice and open-ended questions. The questionnaires were distributed to
      students in different study programs at two universities in Sweden. The present
      result is based on a reanalysis and qualitative analysis formed a key part of the
      study. The results indicate that most of the students' experiences involved group
      work that facilitated learning, especially in the area of academic knowledge.
      Three important prerequisites (learning, study-social function, and organization)
      for group work that served as an effective pedagogy and as an incentive for
      learning were identified and discussed. All three abstractions facilitate or
      hamper students' learning, as well as impact their experiences with group work. 

PMID- 24926283
TI  - Temporal dynamics of cerebral blood flow, cortical damage, apoptosis, astrocyte
      vasculature interaction and astrogliosis in the pericontusional region after
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) results in a loss of brain tissue at the moment of
      impact in the cerebral cortex. Subsequent secondary injury involves the release
      of molecular signals with dramatic consequences for the integrity of damaged
      tissue, leading to the evolution of a pericontusional-damaged area minutes to
      days after in the initial injury. The mechanisms behind the progression of tissue
      loss remain under investigation. In this study, we analyzed the spatial-temporal
      profile of blood flow, apoptotic, and astrocytic-vascular events in the cortical
      regions around the impact site at time points ranging from 5 h to 2 months after
      TBI. We performed a mild-moderate controlled cortical impact injury in young
      adult mice and analyzed the glial and vascular response to injury. We observed a
      dramatic decrease in perilesional cerebral blood flow (CBF) immediately following
      the cortical impact that lasted until days later. CBF finally returned to
      baseline levels by 30 days post-injury (dpi). The initial impact also resulted in
      an immediate loss of tissue and cavity formation that gradually increased in size
      until 3 dpi. An increase in dying cells localized in the pericontusional region
      and a robust astrogliosis were also observed at 3 dpi. A strong vasculature
      interaction with astrocytes was established at 7 dpi. Glial scar formation began
      at 7 dpi and seemed to be compact by 60 dpi. Altogether, these results suggest
      that TBI results in a progression from acute neurodegeneration that precedes
      astrocytic activation, reformation of the neurovascular unit to glial scar
      formation. Understanding the multiple processes occurring after TBI is critical
      to the ability to develop neuroprotective therapeutics to ameliorate the short
      and long-term consequences of brain injury. 

PMID- 24926284
TI  - Behavioral and neurophysiological effects of transdermal rotigotine in atypical
      parkinsonism.
AB  - Effective therapies for the so-called atypical parkinsonian syndrome (APS) such
      as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or
      corticobasal syndrome (CBS) are not available. Dopamine agonists (DA) are not
      often used in APS because of inefficacy and in a minority of case, their side
      effects, like dyskinesias, impairment of extrapyramidal symptoms or the
      appearance of psychosis, and REM sleep behavioral disorders (RBD). Transdermal
      rotigotine (RTG) is a non-ergot dopamine agonist indicated for use in early and
      advanced Parkinson's disease with a good tolerability and safety. Moreover, its
      action on a wide range of dopamine receptors, D1, D2, D3, unlike other DA, could
      make it a good option in APS, where a massive dopamine cell loss is documented.
      In this pilot, observational open-label study we evaluate the efficacy and
      tolerability of RTG in patients affected by APS. Thirty-two subjects with
      diagnosis of APS were treated with transdermal RTG. APS diagnosis was: MSA
      parkinsonian type (MSA-P), MSA cerebellar type (MSA-C), PSP, and CBS. Patients
      were evaluated by UPDRS-III, neuropsychiatric inventory, mini mental state
      examination at baseline, and after 6, 12, and 18 months. The titration schedule
      was maintained very flexible, searching the major clinical effect and the minor
      possible adverse events (AEs) at each visit. AEs were recorded. APS patients
      treated with RTG show an overall decrease of UPDRS-III scores without increasing
      behavioral disturbances. Only three patients were dropped out of the study. Main
      AEs were hypotension, nausea, vomiting, drowsiness, and tachycardia. The
      electroencephalographic recording power spectra analysis shows a decrease of
      theta and an increase of low alpha power. In conclusion, transdermal RTG seems to
      be effective and well tolerated in APS patients. 

PMID- 24926285
TI  - The SCFA Receptor GPR43 and Energy Metabolism.
AB  - Free fatty acids (FFAs) are essential nutrients and act as signaling molecules in
      various cellular processes via binding with FFA receptors. Of these receptors,
      GPR43 is activated by short-chain fatty acids (SCFAs; e.g., acetate, propionate,
      and butyrate). During feeding, SCFAs are produced by microbial fermentation of
      dietary fiber in the gut, and these SCFAs become important energy sources for the
      host. The gut microbiota affects nutrient acquisition and energy regulation of
      the host and can influence the development of obesity, insulin resistance, and
      diabetes. Recently, GPR43 has been reported to regulate host energy homeostasis
      in the gastrointestinal tract and adipose tissues. Hence, GPR43 is also thought
      to be a potential drug target for metabolic disorders, such as obesity and
      diabetes. In this review, we summarize the identification, structure, and
      activities of GPR43, with a focus on host energy regulation, and present an
      essential overview of our current understanding of its physiological roles in
      host energy regulation that is mediated by gut microbiota. We also discuss the
      potential for GPR43 as a therapeutic target. 

PMID- 24926286
TI  - Unraveling the plant microbiome: looking back and future perspectives.
AB  - Most eukaryotes develop close interactions with microorganisms that are essential
      for their performance and survival. Thus, eukaryotes and prokaryotes in nature
      can be considered as meta-organisms or holobionts. Consequently, microorganisms
      that colonize different plant compartments contain the plant's second genome. In
      this respect, many studies in the last decades have shown that plant-microbe
      interactions are not only crucial for better understanding plant growth and
      health, but also for sustainable crop production in a changing world. This mini
      review acting as editorial presents retrospectives and future perspectives for
      plant microbiome studies as well as information gaps in this emerging research
      field. In addition, the contribution of this research topic to the solution of
      various issues is discussed. 

PMID- 24926287
TI  - Salty sisters: The women of halophiles.
AB  - A history of halophile research reveals the commitment of scientists to
      uncovering the secrets of the limits of life, in particular life in high salt
      concentration and under extreme osmotic pressure. During the last 40 years,
      halophile scientists have indeed made important contributions to extremophile
      research, and prior international halophiles congresses have documented both the
      historical and the current work. During this period of salty discoveries, female
      scientists, in general, have grown in number worldwide. But those who worked in
      the field when there were small numbers of women sometimes saw their important
      contributions overshadowed by their male counterparts. Recent studies suggest
      that modern female scientists experience gender bias in matters such as
      conference invitations and even representation among full professors. In the
      field of halophilic microbiology, what is the impact of gender bias? How has the
      participation of women changed over time? What do women uniquely contribute to
      this field? What are factors that impact current female scientists to a greater
      degree? This essay emphasizes the "her story" (not "history") of halophile
      discovery. 

PMID- 24926288
TI  - ESCRT-III mediated cell division in Sulfolobus acidocaldarius - a reconstitution
      perspective.
AB  - In the framework of synthetic biology, it has become an intriguing question what
      would be the minimal representation of cell division machinery. Thus, it seems
      appropriate to compare how cell division is realized in different microorganisms.
      In particular, the cell division system of Crenarchaeota lacks certain proteins
      found in most bacteria and Euryarchaeota, such as FtsZ, MreB or the Min system.
      The Sulfolobaceae family encodes functional homologs of the eukaryotic proteins
      vacuolar protein sorting 4 (Vps4) and endosomal sorting complex required for
      transport-III (ESCRT-III). ESCRT-III is essential for several eukaryotic
      pathways, e.g., budding of intraluminal vesicles, or cytokinesis, whereas Vps4
      dissociates the ESCRT-III complex from the membrane. Cell Division A (CdvA) is
      required for the recruitment of crenarchaeal ESCRT-III proteins to the membrane
      at mid-cell. The proteins polymerize and form a smaller structure during
      constriction. Thus, ESCRT-III mediated cell division in Sulfolobus acidocaldarius
      shows functional analogies to the Z ring observed in prokaryotes like Escherichia
      coli, which has recently begun to be reconstituted in vitro. In this short
      perspective, we discuss the possibility of building such an in vitro cell
      division system on basis of archaeal ESCRT-III. 

PMID- 24926289
TI  - Potential of essential oils for protection of grains contaminated by aflatoxin
      produced by Aspergillus flavus.
AB  - Aflatoxin B1 (AFB1) is a highly toxic and carcinogenic metabolite produced by
      Aspergillus species on food and agricultural commodities. Inhibitory effects of
      essential oils of Ageratum conyzoides (mentrasto) and Origanum vulgare (oregano)
      on the mycelial growth and aflatoxin B1 production by Aspergillus flavus have
      been studied previously in culture medium. The aim of this study was to evaluate
      aflatoxin B1 production by Aspergillus flavus in real food systems (corn and
      soybean) treated with Ageratum conyzoides (mentrasto) and Origanum vulgare
      (oregano) essential oils. Samples with 60 g of the grains were treated with
      different volumes of essential oils, 200, 100, 50, and 10 MUL for oregano and 50,
      30, 15, and 10 MUL for mentrasto. Fungal growth was evaluated by disk diffusion
      method. Aflatoxin B1 production was evaluated inoculating suspensions of A.
      flavus containing 1.3 * 10(5) spores/mL in 60 g of grains (corn and soybeans)
      after adjusting the water activity at 0.94. Aflatoxin was quantified by
      photodensitometry. Fungal growth and aflatoxin production were inhibited by
      essential oils, but the mentrasto oil was more effective in soybeans than that of
      oregano. On the other hand, in corn samples, the oregano essential oil was more
      effective than that of mentrasto. Chemical compositions of the essential oils
      were also investigated. The GC/MS oils analysis showed that the main component of
      mentrasto essential oil is precocene I and of the main component of oregano
      essential oil is 4-terpineol. The results indicate that both essential oils can
      become an alternative for the control of aflatoxins in corn and soybeans. 

PMID- 24926290
TI  - Cytometric fingerprints: evaluation of new tools for analyzing microbial
      community dynamics.
AB  - Optical characteristics of individual bacterial cells of natural communities can
      be measured with flow cytometry (FCM) in high throughput. The resulting data are
      visualized in cytometric histograms. These histograms represent individual
      cytometric fingerprints of microbial communities, e.g., at certain time points or
      microenvironmental conditions. Up to now four tools for analyzing the variation
      in these cytometric fingerprints are available but have not yet been
      systematically compared regarding application: Dalmatian Plot, Cytometric
      Histogram Image Comparison (CHIC), Cytometric Barcoding (CyBar), and FlowFP. In
      this article these tools were evaluated concerning (i) the required experience of
      the operator in handling cytometric data sets, (ii) the detection level of
      changes, (iii) time demand for analysis, and (iv) software requirements. As an
      illustrative example, FCM was used to characterize the microbial community
      structure of electroactive microbial biofilms. Their cytometric fingerprints were
      determined, analyzed with all four tools, and correlated to experimental and
      functional parameters. The source of inoculum (four different types of wastewater
      samples) showed the strongest influence on the microbial community structure and
      biofilm performance while the choice of substrate (acetate or lactate) had no
      significant effect in the present study. All four evaluation tools were found
      suitable to monitor structural changes of natural microbial communities. The
      Dalmatian Plot was shown to be most sensitive to operator impact but nevertheless
      provided an overview on community shifts. CHIC, CyBar, and FlowFP showed less
      operator dependence and gave highly resolved information on community structure
      variation on different detection levels. In conclusion, experimental and
      productivity parameters correlated with the biofilm structures and practical
      process integration details were available from cytometric fingerprint analysis. 

PMID- 24926291
TI  - Advances in detection methods for Shiga toxin-producing Escherichia coli (STEC).

PMID- 24926292
TI  - Bdellovibrio bacteriovorus directly attacks Pseudomonas aeruginosa and
      Staphylococcus aureus Cystic fibrosis isolates.
AB  - Bdellovibrio bacteriovorus is a predator bacterial species found in the
      environment and within the human gut, able to attack Gram-negative prey. Cystic
      fibrosis (CF) is a genetic disease which usually presents lung colonization by
      Pseudomonas aeruginosa or Staphylococcus aureus biofilms. Here, we investigated
      the predatory behavior of B. bacteriovorus against these two pathogenic species
      with: (1) broth culture; (2) "static" biofilms; (3) field emission scanning
      electron microscope (FESEM); (4) "flow" biofilms; (5) zymographic technique. We
      had the first evidence of B. bacteriovorus survival with a Gram-positive prey,
      revealing a direct cell-to-cell contact with S. aureus and a new "epibiotic"
      foraging strategy imaged with FESEM. Mean attaching time of HD100 to S. aureus
      cells was 185 s, while "static" and "flow" S. aureus biofilms were reduced by 74
      (at 24 h) and 46% (at 20 h), respectively. Furthermore, zymograms showed a
      differential bacteriolytic activity exerted by the B. bacteriovorus lysates on P.
      aeruginosa and S. aureus. The dual foraging system against Gram-negative
      (periplasmic) and Gram-positive (epibiotic) prey could suggest the use of B.
      bacteriovorus as a "living antibiotic" in CF, even if further studies are
      required to simulate its in vivo predatory behavior. 

PMID- 24926293
TI  - Antigen-Pulsed CpG-ODN-Activated Dendritic Cells Induce Host-Protective Immune
      Response by Regulating the T Regulatory Cell Functioning in Leishmania donovani
      Infected Mice: Critical Role of CXCL10.
AB  - Visceral leishmaniasis (VL), caused by Leishmania donovani, is a systemic
      infection of reticulo-endothelial system. There is currently no protective
      vaccine against VL and chemotherapy is increasingly limited due to appearance of
      drug resistance to first line drugs such as antimonials and amphotericin B. In
      the present study, by using a murine model of leishmaniasis we evaluated the
      function played by soluble leishmanial antigen (SLA)-pulsed CpG-ODN-stimulated
      dendritic cells (SLA-CpG-DCs) in restricting the intracellular parasitic growth.
      We establish that a single dose of SLA-CpG-DC vaccination is sufficient in
      rendering complete protection against L. donovani infection. In probing the
      possible mechanism, we observe that SLA-CpG-DCs vaccination results in the
      significant decrease in Foxp3(+)GITR(+)CTLA4(+)CD4(+)CD25(+) regulatory T cells
      (Treg) cell population in Leishmania-infected mice. Vaccination with these
      antigen-stimulated dendritic cells results in the decrease in the secretion of
      TGF-beta by these Treg cells by possible regulation of the SMAD signaling.
      Moreover, we demonstrate that a CXC chemokine, IFN-gamma-inducible protein 10 (IP
      10; CXCL10), has a direct role in the regulation of CD4(+)CD25(+) Treg cells in
      SLA-CpG-DC-vaccinated parasitized mice as Treg cells isolated from IP-10-depleted
      vaccinated mice showed significantly increased TGF-beta production and
      suppressive activity. 

PMID- 24926294
TI  - A rapid immunization strategy with a live-attenuated tetravalent dengue vaccine
      elicits protective neutralizing antibody responses in non-human primates.
AB  - Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections
      annually and over 3 billion people worldwide are at risk of infection. No dengue
      vaccine is currently available nor is there an antiviral therapy for DENV
      infections. We have developed a tetravalent live-attenuated DENV vaccine
      tetravalent dengue vaccine (TDV) that consists of a molecularly characterized
      attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre
      membrane and envelope genes of DENV-1, -3, and -4 expressed in the context of the
      TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize
      travelers, a simple and rapid immunization strategy (RIS) is preferred. We
      investigated RIS consisting of two full vaccine doses being administered
      subcutaneously or intradermally on the initial vaccination visit (day 0) at two
      different anatomical locations with a needle-free disposable syringe jet
      injection delivery devices (PharmaJet) in non-human primates. This vaccination
      strategy resulted in efficient priming and induction of neutralizing antibody
      responses to all four DENV serotypes comparable to those elicited by the
      traditional prime and boost (2 months later) vaccination schedule. In addition,
      the vaccine induced CD4(+) and CD8(+) T cells producing IFN-gamma, IL-2, and TNF
      alpha, and targeting the DENV-2 NS1, NS3, and NS5 proteins. Moreover, vaccine
      specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins
      of DENV-4. When animals were challenged with DENV-2 they were protected with no
      detectable viremia, and exhibited sterilizing immunity (no increase of
      neutralizing titers post-challenge). RIS could decrease vaccination visits and
      provide quick immune response to all four DENV serotypes. This strategy could
      increase vaccination compliance and would be especially advantageous for
      travelers into endemic areas. 

PMID- 24926295
TI  - When supply does not meet demand-ER stress and plant programmed cell death.
AB  - The endoplasmic reticulum (ER) is the central organelle in the eukaryotic
      secretory pathway. The ER functions in protein synthesis and maturation and is
      crucial for proper maintenance of cellular homeostasis and adaptation to adverse
      environments. Acting as a cellular sentinel, the ER is exquisitely sensitive to
      changing environments principally via the ER quality control machinery. When
      perturbed, ER-stress triggers a tightly regulated and highly conserved, signal
      transduction pathway known as the unfolded protein response (UPR) that prevents
      the dangerous accumulation of unfolded/misfolded proteins. In situations where
      excessive UPR activity surpasses threshold levels, cells deteriorate and
      eventually trigger programmed cell death (PCD) as a way for the organism to cope
      with dysfunctional or toxic signals. The programmed cell death that results from
      excessive ER stress in mammalian systems contributes to several important
      diseases including hypoxia, neurodegeneration, and diabetes. Importantly,
      hallmark features and markers of cell death that are associated with ER stress in
      mammals are also found in plants. In particular, there is a common, conserved set
      of chaperones that modulate ER cell death signaling. Here we review the elements
      of plant cell death responses to ER stress and note that an increasing number of
      plant-pathogen interactions are being identified in which the host ER is targeted
      by plant pathogens to establish compatibility. 

PMID- 24926297
TI  - Cell wall remodeling in mycorrhizal symbiosis: a way towards biotrophism.
AB  - Cell walls are deeply involved in the molecular talk between partners during
      plant and microbe interactions, and their role in mycorrhizae, i.e., the
      widespread symbiotic associations established between plant roots and soil fungi,
      has been investigated extensively. All mycorrhizal interactions achieve full
      symbiotic functionality through the development of an extensive contact surface
      between the plant and fungal cells, where signals and nutrients are exchanged.
      The exchange of molecules between the fungal and the plant cytoplasm takes place
      both through their plasma membranes and their cell walls; a functional
      compartment, known as the symbiotic interface, is thus defined. Among all the
      symbiotic interfaces, the complex intracellular interface of arbuscular
      mycorrhizal (AM) symbiosis has received a great deal of attention since its first
      description. Here, in fact, the host plasma membrane invaginates and proliferates
      around all the developing intracellular fungal structures, and cell wall material
      is laid down between this membrane and the fungal cell surface. By contrast, in
      ectomycorrhizae (ECM), where the fungus grows outside and between the root cells,
      plant and fungal cell walls are always in direct contact and form the interface
      between the two partners. The organization and composition of cell walls within
      the interface compartment is a topic that has attracted widespread attention,
      both in ecto- and endomycorrhizae. The aim of this review is to provide a general
      overview of the current knowledge on this topic by integrating morphological
      observations, which have illustrated cell wall features during mycorrhizal
      interactions, with the current data produced by genomic and transcriptomic
      approaches. 

PMID- 24926296
TI  - The meiotic transcriptome architecture of plants.
AB  - Although a number of genes that play key roles during the meiotic process have
      been characterized in great detail, the whole process of meiosis is still not
      completely unraveled. To gain insight into the bigger picture, large-scale
      approaches like RNA-seq and microarray can help to elucidate the transcriptome
      landscape during plant meiosis, discover co-regulated genes, enriched processes,
      and highly expressed known and unknown genes which might be important for
      meiosis. These high-throughput studies are gaining more and more popularity, but
      their beginnings in plant systems reach back as far as the 1960's. Frequently,
      whole anthers or post-meiotic pollen were investigated, while less data is
      available on isolated cells during meiosis, and only few studies addressed the
      transcriptome of female meiosis. For this review, we compiled meiotic
      transcriptome studies covering different plant species, and summarized and
      compared their key findings. Besides pointing to consistent as well as unique
      discoveries, we finally draw conclusions what can be learned from these studies
      so far and what should be addressed next. 

PMID- 24926298
TI  - Production of viable seeds from the seedling lethal mutant ppi2-2 lacking the
      atToc159 chloroplast protein import receptor using plastic containers, and
      characterization of the homozygous mutant progeny.
AB  - Biogenesis of chloroplasts is essential for plant growth and development. A
      number of homozygous mutants lacking a chloroplast protein exhibit an albino
      phenotype. In general, it is challenging to grow albino Arabidopsis plants on
      soil until they set seeds. Homozygous albino mutants are usually obtained as
      progenies of heterozygous parents. Here, we describe a method of recovering seeds
      from the seedling lethal Arabidopsis mutant ppi2-2, which lacks the atToc159
      protein import receptor at the outer envelope membrane of chloroplast. Using
      plastic containers, we were able to grow homozygous ppi2-2 plants until these set
      seed. Although the germination rate of the harvested seeds was relatively low, it
      was still sufficient to allow us to further analyze the ppi2-2 progeny. Using
      ppi2-2 homozygous seeds, we were able to analyze the role of plastid protein
      import in the light-regulated induction of nuclear genes. We propose that this
      method be applied to other seedling lethal Arabidopsis mutants to obtain
      homozygous seeds, helping us further investigate the roles of plastid proteins in
      plant growth and development. 

PMID- 24926299
TI  - Allele diversity for abiotic stress responsive candidate genes in chickpea
      reference set using gene based SNP markers.
AB  - Chickpea is an important food legume crop for the semi-arid regions, however, its
      productivity is adversely affected by various biotic and abiotic stresses.
      Identification of candidate genes associated with abiotic stress response will
      help breeding efforts aiming to enhance its productivity. With this objective, 10
      abiotic stress responsive candidate genes were selected on the basis of prior
      knowledge of this complex trait. These 10 genes were subjected to allele specific
      sequencing across a chickpea reference set comprising 300 genotypes including 211
      genotypes of chickpea mini core collection. A total of 1.3 Mbp sequence data were
      generated. Multiple sequence alignment (MSA) revealed 79 SNPs and 41 indels in
      nine genes while the CAP2 gene was found to be conserved across all the
      genotypes. Among 10 candidate genes, the maximum number of SNPs (34) was observed
      in abscisic acid stress and ripening (ASR) gene including 22 transitions, 11
      transversions and one tri-allelic SNP. Nucleotide diversity varied from 0.0004 to
      0.0029 while polymorphism information content (PIC) values ranged from 0.01 (AKIN
      gene) to 0.43 (CAP2 promoter). Haplotype analysis revealed that alleles were
      represented by more than two haplotype blocks, except alleles of the CAP2 and
      sucrose synthase (SuSy) gene, where only one haplotype was identified. These
      genes can be used for association analysis and if validated, may be useful for
      enhancing abiotic stress, including drought tolerance, through molecular
      breeding. 

PMID- 24926300
TI  - Attachment of Agrobacterium to plant surfaces.
AB  - Agrobacterium tumefaciens binds to the surfaces of inanimate objects, plants, and
      fungi. These bacteria are excellent colonizers of root surfaces. In addition,
      they also bind to soil particles and to the surface of artificial or man-made
      substances, such as polyesters and plastics. The mechanisms of attachment to
      these different surfaces have not been completely elucidated. At least two types
      of binding have been described unipolarpolysaccharide-dependent polar attachment
      and unipolar polysaccharide-independent attachment (both polar and lateral). The
      genes encoding the enzymes for the production of the former are located on the
      circular chromosome, while the genes involved in the latter have not been
      identified. The expression of both of these types of attachment is regulated in
      response to environmental signals. However, the signals to which they respond
      differ so that the two types of attachment are not necessarily expressed
      coordinately. 

PMID- 24926301
TI  - The evolution of the actin binding NET superfamily.
AB  - The Arabidopsis Networked (NET) superfamily are plant-specific actin binding
      proteins which specifically label different membrane compartments and identify
      specialized sites of interaction between actin and membranes unique to plants.
      There are 13 members of the superfamily in Arabidopsis, which group into four
      distinct clades or families. NET homologs are absent from the genomes of metazoa
      and fungi; furthermore, in plantae, NET sequences are also absent from the genome
      of mosses and more ancient extant plant clades. A single family of the NET
      proteins is found encoded in the club moss genome, an extant species of the
      earliest vascular plants. Gymnosperms have examples from families 4 and 3, with a
      hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In
      addition to NET3 and 4 families, the NET1 and pollen-expressed NET2 families are
      found only as independent sequences in Angiosperms. This is consistent with the
      divergence of reproductive actin. The four families are conserved across Monocots
      and Eudicots, with the numbers of members of each clade expanding at this point,
      due, in part, to regions of genome duplication. Since the emergence of the NET
      superfamily at the dawn of vascular plants, they have continued to develop and
      diversify in a manner which has mirrored the divergence and increasing complexity
      of land-plant species. 

PMID- 24926302
TI  - Mitogen-activated protein kinase signal transduction and DNA repair network are
      involved in aluminum-induced DNA damage and adaptive response in root cells of
      Allium cepa L.
AB  - In the current study, we studied the role of signal transduction in aluminum
      (Al(3+))-induced DNA damage and adaptive response in root cells of Allium cepa L.
      The root cells in planta were treated with Al(3+) (800 MUM) for 3 h without or
      with 2 h pre-treatment of inhibitors of mitogen-activated protein kinase (MAPK),
      and protein phosphatase. Also, root cells in planta were conditioned with Al(3+)
      (10 MUM) for 2 h and then subjected to genotoxic challenge of ethyl methane
      sulfonate (EMS; 5 mM) for 3 h without or with the pre-treatment of the
      aforementioned inhibitors as well as the inhibitors of translation,
      transcription, DNA replication and repair. At the end of treatments, roots cells
      were assayed for cell death and/or DNA damage. The results revealed that Al(3+)
      (800 MUM)-induced significant DNA damage and cell death. On the other hand,
      conditioning with low dose of Al(3+) induced adaptive response conferring
      protection of root cells from genotoxic stress caused by EMS-challenge. Pre
      treatment of roots cells with the chosen inhibitors prior to Al(3+)-conditioning
      prevented or reduced the adaptive response to EMS genotoxicity. The results of
      this study suggested the involvement of MAPK and DNA repair network underlying Al
      induced DNA damage and adaptive response to genotoxic stress in root cells of A.
      cepa. 

PMID- 24926303
TI  - The nucleoid as a site of rRNA processing and ribosome assembly.

PMID- 24926304
TI  - Across a macro-ecological gradient forest competition is strongest at the most
      productive sites.
AB  - We tested the hypothesis that the effect of forest basal area on tree growth
      interacts with macro-ecological gradients of primary productivity, using a large
      dataset of eucalypt tree growth collected across temperate and sub- tropical
      mesic Australia. To do this, we derived an index of inter-tree competition based
      on stand basal area (stand BA) relative to the climatically determined potential
      basal area. Using linear mixed effects modeling, we found that the main effects
      of climatic productivity, tree size, and competition explained 26.5% of the
      deviance in individual tree growth, but adding interactions to the model could
      explain a further 8.9%. The effect of competition on growth interacts with the
      gradient of climatic productivity, with negligible effect of competition in low
      productivity environments, but marked negative effects at the most productive
      sites. We also found a positive interaction between tree size and stand BA, which
      was most pronounced in the most productive sites. We interpret these patterns as
      reflecting intense competition for light amongst maturing trees on more
      productive sites, and below ground moisture limitation at low productivity sites,
      which results in open stands with little competition for light. These trends are
      consistent with the life history and stand development of eucalypt forests: in
      cool moist environments, light is the most limiting resource, resulting in size
      asymmetric competition, while in hot, low rainfall environments are open forests
      with little competition for light but where the amount of tree regeneration is
      limited by water availability. 

PMID- 24926305
TI  - The smoking paradox: impact of smoking on recanalization in the setting of intra
      arterial thrombolysis.
AB  - BACKGROUND: The smoking paradox refers to a better outcome in smokers eligible
      for thrombolytic treatment in myocardial infarction or ischemic stroke. Recent
      findings suggest that current smokers may present higher recanalization rates
      after intravenous (IV) thrombolysis with recombinant tissue plasminogen activator
      (rt-PA). We evaluated the impact of smoking in a consecutive series of patients
      treated with intra-arterial (IA) rt-PA. METHODS: We analyzed data collected
      between April 2007 and December 2012 in our prospective registry. All acute
      ischemic stroke patients with an arterial occlusion treated by IA rt-PA (+/- IV,
      +/- thrombectomy) were included. Arterial status was monitored with conventional
      angiography during the IA procedure. The primary study outcome was a complete
      recanalization achieved immediately after termination of IA rt-PA infusion.
      Secondary outcomes included complete recanalization after the end of the
      endovascular therapy (including complete recanalization achieved after adjunctive
      thrombectomy), favorable outcome (90-day modified Rankin Score <=2), 90-day all
      cause mortality, and any intracerebral hemorrhage. RESULTS: Among the 227
      included patients, 18.5% (n = 42) were current smokers and 16.7% (n = 38) former
      smokers. Compared with nonsmokers, current smokers were younger, more often men,
      had less frequently hypertension, and cardioembolic etiology, whereas former
      smokers were more often men and had more frequently hypercholesterolemia. The
      rate of complete recanalization was 30% (n = 68) after IA rt-PA infusion and 49%
      after adjunctive thrombectomy. A higher complete recanalization rate was found
      both in current smokers (45.2%) and former smokers (42.1%) compared to nonsmokers
      (22.5%). After adjustment for potential confounders, the adjusted odds ratio (OR)
      for complete recanalization associated with ever-smokers was 2.51 [95% confidence
      interval (CI) 1.26-4.99; p = 0.009]. A similar adjusted OR was found when the
      complete recanalization achieved after thrombectomy was included (OR 2.18, 95% CI
      1.13-4.19; p = 0.019). However, smoking status was not independently associated
      with favorable outcome (adjusted OR 1.41, 95% CI 0.62-3.22 for former smokers,
      and adjusted OR 1.35, 95% CI 0.59-3.05 for current smokers), 90-day all-cause
      mortality (adjusted OR 0.68, 95% CI 0.25-1.81 for former smokers, and adjusted OR
      1.55, 95% CI 0.54-4.48 for current smokers) or intracerebral hemorrhage (adjusted
      OR 0.72, 95% CI 0.29-1.76 for former smokers, and adjusted OR 0.80, 95% CI 0.32
      1.96 for current smokers). CONCLUSIONS: IA rt-PA administration was more
      effective to achieve complete arterial recanalization in current as well as
      former smokers. The characterization of the smoking paradox pathophysiology may
      lead to the identification of a patient-target population with a favorable
      response to rt-PA therapy. However, the smoking paradox should not be
      misinterpreted and not be used to promote smoking.

PMID- 24926306
TI  - Aortic arch atherosclerosis in ischaemic stroke of unknown origin affects
      prognosis.
AB  - BACKGROUND: Cerebral infarction of unknown origin at admission accounts for half
      of all cerebral infarction cases in some institutions. However, the factors
      associated with cerebral infarction prognosis have not been sufficiently
      examined. Here, we investigated whether aortic arch plaques (AAPs) on
      transoesophageal echocardiography (TOE) were associated with the prognosis of
      cerebral infarction of unknown origin at admission. METHODS: Of 571 patients who
      were hospitalised between June 2009 and September 2011, 149 (age: 67 +/- 14
      years; 95 men) with cerebral infarctions of unknown origin at admission underwent
      TOE and were enrolled in this study. We examined their clinical characteristics,
      the incidence of intermittent atrial fibrillation detected on 24-hour
      electrocardiography, and the echographic findings of the carotid artery in the
      hospital. A poor prognostic outcome was defined as a modified Rankin Scale score
      of >=3 after 90 days. RESULTS: In all, 110 patients (74%) showed good prognoses
      and 39 patients (26%) showed poor outcomes. A National Institutes of Health
      Stroke Scale score of >6 on admission [odds ratio (OR) = 6.77; 95% confidence
      interval (CI): 2.59-18.8; p < 0.001] and AAPs of >=4 mm (OR = 2.75; 95% CI: 1.19
      6.91; p = 0.024) showed significant associations with a poor prognosis of
      cerebral infarction of unknown origin at admission. CONCLUSIONS: Thick AAPs could
      be a factor in the prediction of a poor prognosis of cerebral infarction of
      unknown origin at admission. The establishment of international standards for
      aortogenic brain embolisms is required. Future prospective studies should examine
      cerebral infarctions of unknown origin.

PMID- 24926307
TI  - Subcortical and Deep Cortical Atrophy in Frontotemporal Dementia due to Granulin
      Mutations.
AB  - BACKGROUND/AIMS: Parkinsonism is often associated with symptoms of frontotemporal
      dementia (FTD), but its pathogenesis has been largely neglected. In genetic
      inherited FTD-related granulin (GRN) mutations, parkinsonism is an early sign,
      and it is more common than in sporadic disorders. Our aim was to study grey
      matter (GM) volume changes in subcortical and deep cortical regions in GRN
      related FTD. METHODS: A total of 33 FTD patients (13 carriers of the GRN
      mutation, GRN+, and 20 non-carriers, GRN-) and 12 healthy controls (HC) were
      included in the study. Each subject underwent an MRI examination (1) for voxel
      based morphometry to study GM differences in cortical and subcortical regions,
      and (2) for a region of interest approach using a probabilistic atlas of
      subcortical regions (caudate nucleus, putamen, thalamus and amygdala) to assess
      the regional differences. RESULTS: The GRN+ group showed greater damage in
      frontotemporal regions than the GRN- group. The FTD patients had greater GM
      atrophy in the caudate nucleus and in the thalamus bilaterally than the HC.
      Damage to these subcortical and deep cortical regions was greater in the GRN+
      than in the GRN- patients. DISCUSSION: Subcortical and deep cortical involvement
      is a key feature of FTD, and more pronounced in GRN-related disease. Damage to
      the caudate region in GRN+ patients may explain the parkinsonism frequently
      associated since the early stages of the disease.

PMID- 24926308
TI  - Decreased motor function is associated with poorer cognitive function in elderly
      with type 2 diabetes.
AB  - BACKGROUND/AIMS: Impaired motor function has been associated with cognitive
      impairment and dementia, but this relationship is poorly understood in elderly
      with type 2 diabetes (T2D). We thus investigated it in a large sample (n = 726)
      of cognitively normal elderly with T2D. METHODS: In this cross-sectional study,
      hierarchical linear regressions assessed correlations of 3 motor measures (timed
      walk, grip strength, and self-reported motor difficulties) with episodic memory,
      attention/working memory, semantic categorization, executive function, and
      overall cognition controlling for demographics. RESULTS: Longer timed walk and
      weaker grip strength were associated with poorer performance in all cognitive
      domains except episodic memory. CONCLUSIONS: Associations of motor and cognitive
      functions in T2D and non-T2D samples are consistent. A lack of association of
      motor function with episodic memory may suggest non-Alzheimer's disease-related
      underlying mechanisms.

PMID- 24926309
TI  - Focal Segmental Glomerulosclerosis Secondary to Juxtaglomerular Cell Tumor during
      Pregnancy: A Case Report.
AB  - Juxtaglomerular cell tumor is a rare renal neoplasm. Secondary hypertension with
      juxtaglomerular cell tumor can be seen in females in their 20s and 30s. We
      present a case of juxtaglomerular cell tumor during pregnancy. A 32-year-old
      female was hospitalized for refractory hypertension and nephrotic syndrome in the
      23rd gestational week. One year before admission, she had been diagnosed with
      hypertension; plasma renin activity at that time had been 2.3 ng/ml/h. Her blood
      pressure was uncontrolled during pregnancy, and proteinuria was detected in the
      12th gestational week despite the administration of antihypertensive medications.
      Laboratory data showed proteinuria, hypokalemia, and hypoalbuminemia. In the 25th
      gestational week, she underwent surgical termination of the pregnancy because of
      congestive heart failure and acute renal injury. After the termination of the
      pregnancy and the delivery of a viable fetus, her hypertension and nephrotic
      syndrome were found to persist with a high plasma renin activity (13 ng/ml/h).
      Ultrasonography showed a 5.5-cm left renal cystic mass with a partially solid
      component at the lower renal pole. The left kidney with the renal mass was
      excised by laparoscopic nephrectomy. Plasma renin activity normalized the next
      day, with a decrease in blood pressure to 120-130/80-90 mm Hg; however,
      proteinuria remained at >=3.5 g/day. On the basis of histopathological findings,
      the patient was diagnosed with a juxtaglomerular cell tumor and focal segmental
      glomerulosclerosis. Juxtaglomerular cell tumor is a rare renin-secreting tumor
      associated with refractory hypertension in young females and is a possible cause
      of hypertension during pregnancy. 

PMID- 24926310
TI  - Dialysis and quality of dialysate in southeast asian developing countries.
AB  - BACKGROUND: The number of dialysis patients has been increasing in Southeast
      Asia, but statistical data about these patients and on the quality of dialysates
      in Southeast Asian dialysis facilities are still imprecise. For this study,
      dialysis-related statistical data were collected in Southeast Asia. METHODS: A
      survey of the quality of dialysates was carried out at 4 dialysis facilities in
      Vietnam and Cambodia. The dialysis patient survey included the numbers of
      dialysis facilities and patients receiving dialysis, a ranking of underlying
      diseases causing the initiation of dialysis, the number of patients receiving
      hemodialysis (HD)/on-line hemodiafiltration/continuous ambulatory peritoneal
      dialysis, the number of HD monitoring devices installed, the cost of each session
      of dialysis (in USD), the percentage of out-of-pocket payments, and the 1-year
      survival rates of the dialysis patients (in percent). The dialysate survey
      covered the endotoxin (ET) level and bacterial count in tap water, in water
      filtered through a reverse osmosis system and in dialysate. RESULTS: In each of
      the countries, the most frequent reason for the initiation of dialysis is
      diabetes mellitus. HD is usually carried out according to the 'reuse' principle.
      The 1-year survival rates are 70% in Myanmar and about 90% in the Philippines and
      Malaysia. The ET levels in standard dialysates were satisfactory at 2 facilities.
      The bacterial counts in dialysates were not acceptable at any of the facilities
      investigated. CONCLUSION: There is an urgent need to teach medical workers
      involved in dialysis how to prepare sterile and ET-free dialysates.

PMID- 24926311
TI  - Kidney Diseases Enhance Expression of Tetraspanin-8: A Possible Protective Effect
      against Tubular Injury.
AB  - BACKGROUND/AIMS: TSPAN8 encoding tetraspanin-8 was identified as a candidate gene
      for immunoglobulin A nephropathy (IgAN) by a genome-wide association study using
      microsatellites in the Japanese population. Tetraspanin-8 is a cell surface
      protein that contributes to the migration and invasion of epithelial cells.
      METHODS: We performed immunohistochemistry for tetraspanin-8 on human renal
      biopsy specimens associated with IgAN, antineutrophil cytoplasmic antibody
      associated nephropathy and interstitial nephritis, as well as normal renal
      tissue. Furthermore, to study the potential function of tetraspanin-8, we
      performed cell migration and invasion assays using human renal tubule cells
      transfected with tetraspanin-8. RESULTS: Tetraspanin-8 was often expressed in
      vascular smooth muscle cells and occasionally in tubule cells in normal kidney.
      In the kidneys of all types of nephropathy, tetraspanin-8 staining in the
      arteries was unaffected, but that in the tubules was enhanced. The degree of
      tubular staining negatively correlated with the estimated glomerular filtration
      rate, independently of the type of nephropathy. Tetraspanin-8-expressing tubule
      cells were found predominantly in distal and collecting tubules, identified by
      cytokeratin 7 or aquaporin 2 staining. In vitro studies using cultured tubule
      cells revealed that tetraspanin-8 promoted migration by 2.7-fold without laminin,
      by 2.8-fold with laminin and invasion into Matrigel by 3.5-fold, suggesting that
      enhanced tetraspanin-8 may be involved in the repair of tubules. CONCLUSION: The
      obtained findings indicate that tetraspanin-8 expression is enhanced in injured
      distal tubules, which may be involved in the repair of tubules by facilitating
      migration and invasion.

PMID- 24926312
TI  - Can Nephrologists Use Ultrasound to Evaluate the Inferior Vena Cava? A Cross
      Sectional Study of the Agreement between a Nephrologist and a Cardiologist.
AB  - BACKGROUND/AIMS: The costs and the need for a specialist impair the
      implementation of ultrasonography for evaluating the inferior vena cava (IVC) to
      assess the volemic status in hemodialysis patients. We investigated whether a
      nephrologist with limited ultrasound training can accurately assess the IVC in
      patients undergoing hemodialysis. METHODS: A cardiologist and a nephrologist
      consecutively measured the indexed IVC expiratory diameter (VCDi) and the IVC
      collapsibility index (IVCCI) of 52 patients during hemodialysis sessions. In
      protocol I, the nephrologist used a regular ultrasound system (RUS) and the
      cardiologist used a cardiovascular ultrasound equipment; in protocol II, the
      machines were interchanged. Pearson and kappa coefficients and the interexaminer
      agreement by the Bland-Altman method were calculated. RESULTS: The VCDi
      measurements showed a strong correlation in both protocols (r = 0.88 and 0.84 in
      protocols I and II, respectively). The volemic classifications were excellent in
      protocol I (kappa = 0.82 and 0.93 by VCDi and IVCCI, respectively) and
      substantial in protocol II (kappa = 0.77 and 0.75 by VCDi and IVCCI,
      respectively). The interexaminer agreement on the VCDi measurements was very good
      in both protocols. CONCLUSIONS: Ultrasound evaluation of the IVC can be performed
      by nephrologists using an RUS to assess the volemic status in hemodialysis
      patients.

PMID- 24926313
TI  - Longevity pathways and memory aging.
AB  - The aging process has been associated with numerous pathologies at the cellular,
      tissue, and organ level. Decline or loss of brain functions, including learning
      and memory, is one of the most devastating and feared aspects of aging. Learning
      and memory are fundamental processes by which animals adjust to environmental
      changes, evaluate various sensory signals based on context and experience, and
      make decisions to generate adaptive behaviors. Age-related memory impairment is
      an important phenotype of brain aging. Understanding the molecular mechanisms
      underlying age-related memory impairment is crucial for the development of
      therapeutic strategies that may eventually lead to the development of drugs to
      combat memory loss. Studies in invertebrate animal models have taught us much
      about the physiology of aging and its effects on learning and memory. In this
      review we survey recent progress relevant to conserved molecular pathways
      implicated in both aging and memory formation and consolidation. 

PMID- 24926314
TI  - Targeting molecular networks for drug research.
AB  - The study of molecular networks has recently moved into the limelight of
      biomedical research. While it has certainly provided us with plenty of new
      insights into cellular mechanisms, the challenge now is how to modify or even
      restructure these networks. This is especially true for human diseases, which can
      be regarded as manifestations of distorted states of molecular networks. Of the
      possible interventions for altering networks, the use of drugs is presently the
      most feasible. In this mini-review, we present and discuss some exemplary
      approaches of how analysis of molecular interaction networks can contribute to
      pharmacology (e.g., by identifying new drug targets or prediction of drug side
      effects), as well as list pointers to relevant resources and software to guide
      future research. We also outline recent progress in the use of drugs for in vitro
      reprogramming of cells, which constitutes an example par excellence for altering
      molecular interaction networks with drugs. 

PMID- 24926315
TI  - Genetic variation in the 3'-UTR of CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and
      UGT2B7: potential effects on regulation by microRNA and pharmacogenomics
      relevance.
AB  - INTRODUCTION: Pharmacogenomics research has concentrated on variation in genes
      coding for drug metabolizing enzymes, transporters and nuclear receptors.
      However, variation affecting microRNA could also play a role in drug response.
      This project set out to investigate potential microRNA target sites in 11 genes
      and the extent of variation in the 3'-UTR of six selected genes; CYP1A2, CYP2B6,
      CYP2D6, CYP3A4, NR1I2, and UGT2B7. METHODS: Fifteen microRNA target prediction
      algorithms were used to identify microRNAs predicted to regulate 11 genes. The 3'
      UTR of the 6 genes which topped the list of potential microRNA targets was
      sequenced in 30 black South Africans. In addition, genetic variants within these
      genes were investigated for interference with mRNA-microRNA interactions.
      Potential effects of observed variants were determined using in silico prediction
      tools. RESULTS: The 11 genes coding for DMEs, transporters and nuclear receptors
      were predicted to be targets of microRNAs with CYP2B6, NR1I2 (PXR), CYP3A4, and
      CYP1A2, interacting with the most microRNAs. The majority of identified genetic
      variants were predicted to interfere with microRNA regulation. For example, the
      variant, rs1054190C in NR1I2 was predicted to result in the presence of a binding
      site for the microRNA miR-1250-5p, while the variant rs1054191G was predicted to
      result in the absence of a recognition site for miR-371b-3p, miR-4258 and miR
      4707-3p. Fifteen of the seventeen, novel variants occurred within microRNA target
      sequences. CONCLUSION: The 3'-UTR harbors variation that is likely to influence
      regulation of specific genes by microRNA. In silico prediction followed by
      functional validation could aid in decoding the contribution of variation in the
      3'-UTR, to some unexplained heritability that affects drug response.
      Understanding the specific role of each microRNA may lead to identification of
      markers for targeted therapy and therefore improve personalized drug treatment.

PMID- 24926316
TI  - Culturing intestinal stem cells: applications for colorectal cancer research.
AB  - Recent advance of sequencing technology has revealed genetic alterations in
      colorectal cancer (CRC). The biological function of recurrently mutated genes has
      been intensively investigated through mouse genetic models and CRC cell lines.
      Although these experimental models may not fully reflect biological traits of
      human intestinal epithelium, they provided insights into the understanding of
      intestinal stem cell self-renewal, leading to the development of novel human
      intestinal organoid culture system. Intestinal organoid culture enabled to expand
      normal or tumor epithelial cells in vitro retaining their stem cell self-renewal
      and multiple differentiation. Gene manipulation of these cultured cells may
      provide an attractive tool for investigating genetic events involved in
      colorectal carcinogenesis. 

PMID- 24926317
TI  - Copulation or sensory cues from the female augment Fos expression in arginine
      vasopressin neurons of the posterodorsal medial amygdala of male rats.
AB  - BACKGROUND: The posterodorsal part of the medial amygdala is essential for
      processing reproductively salient sensory information in rodents. This is the
      initial brain structure where information from olfactory system and male hormones
      intersect. The neurochemical identity of the neurons participating in the sensory
      processing in medial amygdala remains presently undetermined. Many neurons in
      this brain structure express arginine vasopressin in a testosterone-dependent
      manner, suggesting that this neuropeptide is maintained by the androgenic milieu.
      METHOD: Here we use Fos, a protein expressed by recently active neurons, to
      quantify activation of arginine vasopressin neurons after exposure to odor from
      physically inaccessible female. We compare it to mating with accessible female
      and to reproductively innocuous odor. RESULTS: We show that inaccessible female
      activate arginine vasopressin neurons in the male posterodorsal medial amygdala.
      The magnitude of activation is not further enhanced when physical access with
      resultant mating is granted, even though it remains undetermined if same
      population of AVP neurons is activated by both inaccessible female and
      copulation. We also show that arginine vasopressin activation cannot be fully
      accounted for by mere increase in the number of Fos and AVP neurons. CONCLUSION:
      These observations posit a role for the medial amygdala arginine vasopressin in
      reproductive behaviors, suggesting that these neurons serve as integrative node
      between the hormonal status of the animal and the availability of reproductive
      opportunities.

PMID- 24926318
TI  - The effect of compliance to a Rigo System Cheneau brace and a specific exercise
      programme on idiopathic scoliosis curvature: a comparative study: SOSORT 2014
      award winner.
AB  - BACKGROUND: There is controversy as to whether conservative management that
      includes wearing a brace and exercises is effective in stabilising idiopathic
      scoliosis curves. A brace only prevents progression of the curve and has been
      shown to have favourable outcomes when patients are compliant. So the aim of this
      study was to: determine the effect of compliance to the Rigo System Cheneau (RSC)
      brace and a specific exercise programme on Idiopathic Scoliosis curvature; and to
      compare the Quality of Life (QoL) and psychological traits of compliant and non
      compliant subjects. METHODS: A pre/post test study design was used with a post
      study comparison between subjects who complied with the management and those who
      did not. Fifty one subjects, girls aged 12-16 years, Cobb angles 20-50 degrees
      participated in the study. Subjects were divided into two groups, according to
      their compliance, at the end of the study. The compliant group wore the brace 20
      or more hours a day and exercised three or more times per week. The non-compliant
      group wore the brace less than 20 hours a day and exercised less than three times
      per week. Cobb angles, vertebral rotation, scoliometer readings, peak flow,
      quality of life and personality traits were compared between groups, using the
      student's two sample t-test and an analysis of covariance. RESULTS: The compliant
      group, wore the brace 21.5 hours per day and exercised four times a week, and
      significantly improved in all measures compared to non compliant subjects, who
      wore the brace 12 hours per day, exercised 1.7 times a week and significantly
      deteriorated (p < 0.0001). The major Cobb angles in the compliant group improved
      10.19 degrees (+/-5.5) and deteriorated 5.52 degrees (+/-4.3) in the non
      compliant group (p < 0.0001). Compliant subjects had a significantly better QoL
      than the non compliant subjects (p = 0.001). The compliant group were
      significantly more emotionally mature, stable and realistic than the non
      compliant group (p = 0.03). CONCLUSIONS: Good compliance of the RSC brace and a
      specific exercise regime resulted in a significant improvement in curvatures,
      poor compliance resulted in progression/deterioration. A poorer QoL in the non
      compliant group possibly was caused by personality traits of the group, being
      more emotionally immature and unstable.

PMID- 24926319
TI  - Performance of chromosomal microarray for patients with intellectual
      disabilities/developmental delay, autism, and multiple congenital anomalies in a
      Chinese cohort.
AB  - BACKGROUND: Chromosomal microarray (CMA) is currently the first-tier genetic test
      for patients with idiopathic neuropsychiatric diseases in many countries. Its
      improved diagnostic yield over karyotyping and other molecular testing
      facilitates the identification of the underlying causes of neuropsychiatric
      diseases. In this study, we applied oligonucleotide array comparative genomic
      hybridization as the molecular genetic test in a Chinese cohort of children with
      DD/ID, autism or MCA. RESULTS: CMA identified 7 clinically significant
      microduplications and 17 microdeletions in 19.0% (20/105) patients, with size of
      aberrant regions ranging from 11 kb to 10.7 Mb. Fourteen of the pathogenic copy
      number variant (CNV) detected corresponded to well known microdeletion or
      microduplication syndromes. Four overlapped with critical regions of recently
      identified genomic syndromes. We also identified a rare de novo 2.3 Mb deletion
      at 8p21.3-21.2 as a pathogenic submicroscopic CNV. We also identified two novel
      CNVs, one at Xq28 and the other at 12q21.31-q21.33, in two patients (1.9%) with
      unclear clinical significance. Overall, the detection rate of CMA is comparable
      to figures previously reported for accurately detect submicroscopic chromosomal
      imbalances and pathogenic CNVs except mosaicism, balanced translocation and
      inversion. CONCLUSIONS: This study provided further evidence of an increased
      diagnostic yield of CMA and supported its use as a first line diagnostic tool for
      Chinese individuals with DD/ID, ASD, and MCA.

PMID- 24926320
TI  - Prevalence and clinical characteristics of lower limb atherosclerotic lesions in
      newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.
AB  - BACKGROUND: The clinical features of atherosclerotic lesions in ketosis-onset
      diabetes are largely absent. We aimed to compare the characteristics of lower
      limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2
      diabetes. METHODS: A cross-sectional study was performed in newly diagnosed
      Chinese patients with diabetes, including 53 type 1 diabetics with positive islet
      associated autoantibodies, 208 ketosis-onset diabetics without islet-associated
      autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without
      diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb
      atherosclerotic plaque and stenosis were evaluated and compared among the four
      groups based on ultrasonography. The risk factors associated with lower limb
      atherosclerotic plaque were evaluated via binary logistic regression in patients
      with diabetes. RESULTS: After adjusting for age and sex, the prevalence of lower
      limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly
      higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend
      compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no
      difference was observed in comparison to the patients with non-ketotic type 2
      diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73
      +/- 0.17 mm) was markedly greater than that in the control subjects (0.69 +/-
      0.13 mm, p = 0.045) after controlling for age and sex, but no significant
      differences were found between the ketosis-onset diabetics and the type 1
      diabetics (0.71 +/- 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics
      (0.80 +/- 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk
      factors for the presence of lower limb plaque in both the ketosis-onset and non
      ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic
      patients. CONCLUSIONS: The prevalence and risk of lower limb atherosclerotic
      plaque in the ketosis-onset diabetes were remarkably higher than in the control
      subjects without diabetes. The features and risk factors of lower limb
      atherosclerotic lesions in the ketosis-onset diabetes resembled those in the non
      ketotic type 2 diabetes, but different from those in the type 1 diabetes. Our
      findings provide further evidences to support the classification of ketosis-onset
      diabetes as a subtype of type 2 diabetes rather than idiopathic type 1 diabetes.

PMID- 24926321
TI  - Co-benefits of Global Greenhouse Gas Mitigation for Future Air Quality and Human
      Health.
AB  - Actions to reduce greenhouse gas (GHG) emissions often reduce co-emitted air
      pollutants, bringing co-benefits for air quality and human health. Past studies1
      6 typically evaluated near-term and local co-benefits, neglecting the long-range
      transport of air pollutants7-9, long-term demographic changes, and the influence
      of climate change on air quality10-12. Here we simulate the co-benefits of global
      GHG reductions on air quality and human health using a global atmospheric model
      and consistent future scenarios, via two mechanisms: a) reducing co-emitted air
      pollutants, and b) slowing climate change and its effect on air quality. We use
      new relationships between chronic mortality and exposure to fine particulate
      matter13 and ozone14, global modeling methods15, and new future scenarios16.
      Relative to a reference scenario, global GHG mitigation avoids 0.5+/-0.2, 1.3+/
      0.5, and 2.2+/-0.8 million premature deaths in 2030, 2050, and 2100. Global
      average marginal co-benefits of avoided mortality are $50-380 (ton CO2)-1, which
      exceed previous estimates, exceed marginal abatement costs in 2030 and 2050, and
      are within the low range of costs in 2100. East Asian co-benefits are 10-70 times
      the marginal cost in 2030. Air quality and health co-benefits, especially as they
      are mainly local and near-term, provide strong additional motivation for
      transitioning to a low-carbon future.

PMID- 24926322
TI  - Tc1-like transposable elements in plant genomes.
AB  - BACKGROUND: The Tc1/mariner superfamily of transposable elements (TEs) is
      widespread in animal genomes. Mariner-like elements, which bear a DDD triad
      catalytic motif, have been identified in a wide range of flowering plant species.
      However, as the founding member of the superfamily, Tc1-like elements that bear a
      DD34E triad catalytic motif are only known to unikonts (animals, fungi, and
      Entamoeba). RESULTS: Here we report the identification of Tc1-like elements
      (TLEs) in plant genomes. These elements bear the four terminal nucleotides and
      the characteristic DD34E triad motif of Tc1 element. The two TLE families (PpTc1,
      PpTc2) identified in the moss (Physcomitrella patens) genome contain highly
      similar copies. Multiple copies of PpTc1 are actively transcribed and the
      transcripts encode intact full length transposase coding sequences. TLEs are also
      found in angiosperm genome sequence databases of rice (Oryza sativa), dwarf birch
      (Betula nana), cabbage (Brassica rapa), hemp (Cannabis sativa), barley (Hordium
      valgare), lettuce (Lactuta sativa), poplar (Populus trichocarpa), pear (Pyrus x
      bretschneideri), and wheat (Triticum urartu). CONCLUSIONS: This study extends the
      occurrence of TLEs to the plant phylum. The elements in the moss genome have
      amplified recently and may still be capable of transposition. The TLEs are also
      present in angiosperm genomes, but apparently much less abundant than in moss.

PMID- 24926323
TI  - p27 modulates tropism of mesenchymal stem cells toward brain tumors.
AB  - Mesenchymal stem cells (MSCs) have inherent tumor-tropic properties in the brain
      and seem to be a useful tool for cellular therapy for brain tumors. However, the
      mechanisms involved in MSC migration are not fully understood. The tumor
      suppressor p27, an inhibitor of cyclin-dependent kinase complexes, not only plays
      a crucial role in cell cycle regulation but also has cell cycle-independent
      functions, such as differentiation and migration of cells. In fact, p27 has been
      alternatively reported to inhibit or stimulate cell migration in cells of
      different types. Therefore, in the present study, we investigated whether p27 is
      involved in the tumor-tropic activity of MSCs using MSCs from p27-null mice. It
      was found that p27-/- MSCs showed a decreased motility in the wound healing assay
      and displayed increased numbers of stress fibers. To compare the in vivo
      migratory activity of p27-/- and p27+/+ MSCs toward glioma, we injected C6 glioma
      cells into one side of the mouse brain and BrdU-labeled p27-/- or p27+/+ MSCs
      into the other side. Significantly fewer labeled p27-/- MSCs were observed in the
      tumor area compared with p27+/+ MSCs. The present study suggests that p27 works
      as a stimulator of the in vitro and in vivo migration process of MSCs toward
      tumors. These findings are important when the efficacy of stem cell-based
      strategies for glioma therapy is considered.

PMID- 24926324
TI  - Pigmented paravenous retinochoroidal atrophy (Review).
AB  - Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon disease
      characterized by perivenous aggregations of pigment clumps associated with
      peripapillary and radial zones of retinochoroidal atrophy that are distributed
      along the retinal veins. Patients are usually asymptomatic and the disease
      process is non-progressive or slow and subtly progressive. It is commonly
      bilateral and symmetric. The cause of the condition may be unknown or idiopathic,
      although a dysgenetic, degenerative, hereditary etiology or even an inflammatory
      cause has been hypothesized. A non-inflammatory cause is referred to as primary,
      while inflammation-associated PPRCA is referred to as secondary or pseudo PPRCA.
      The present study reviewed and summarized the features of PPRCA.

PMID- 24926325
TI  - Effect of salidroside on lung injury by upregulating peroxisome proliferator
      activated receptor gamma expression in septic rats.
AB  - Successful drug treatment for sepsis-related acute lung injury (ALI) remains a
      major clinical problem. Thus, the aim of the present study was to investigate the
      beneficial effects of salidroside on ameliorating cecal ligation and puncture
      (CLP)-induced lung inflammation. Rats underwent CLP surgery to induce ALI and 800
      mg/kg salidroside (i.v.) was administered 24 h after the CLP challenge.
      Subsequently, biochemical changes in the blood and lung tissues, as well as
      morphological and histological alterations in the lungs, that were associated
      with inflammation and injury were analysed. CLP was shown to significantly
      increase the serum levels of plasma tumour necrosis factor-alpha and interleukin
      6, -1beta and-10. In addition, CLP increased pulmonary oedema, thickened the
      alveolar septa and caused inflammation in the lung cells. These changes were
      ameliorated by the administration of 800 mg/kg salidroside (i.v.) 24 h after the
      CLP challenge. This post-treatment drug administration also significantly
      attenuated the lipopolysaccharide-induced activation of nuclear factor-kappabeta
      and increased the release of peroxisome proliferator-activated receptor gamma in
      the lung tissue. Therefore, salidroside administered following the induction of
      ALI by CLP significantly prevented and reversed lung tissue injuries. The
      positive post-treatment effects of salidroside administration indicated that
      salidroside may be a potential candidate for the management of lung inflammation
      in CLP-induced endotoxemia and septic shock.

PMID- 24926326
TI  - Reduction of left ventricular longitudinal global and segmental systolic
      functions in patients with hypertrophic cardiomyopathy: Study of two-dimensional
      tissue motion annular displacement.
AB  - The early detection of abnormal left ventricular systolic functions in patients
      with hypertrophic cardiomyopathy (HCM) remains a challenge. The aim of this study
      was to identify a novel method for the assessment of left ventricular systolic
      function in patients with HCM. A total of 65 patients with HCM were included in
      this study. The patients were divided into obstructive HCM (HOCM; 16 cases) and
      non-obstructive HCM (NOHCM; 49 cases) groups. The healthy control group comprised
      48 participants. Two-dimensional (2D) speckle-tracking technology was used to
      measure the left ventricular global and segmental longitudinal strains and mitral
      annular displacement (MADs). Compared with healthy control group, the six
      segmental strains and the global strain of the left ventricle (LSglobal)
      increased while six segmental MADs and MADglobal of the mitral annulus decreased
      in the HOCM and NOHCM groups (P<0.05). In addition, the six segmental MADs of the
      mitral annulus were significantly negatively correlated with the six segmental
      strains of the left ventricle (r=-0.744 to -0.647, P<0.001). MADglobal was
      significantly negatively correlated with LSglobal (r=-0.857, P<0.001). The tissue
      motion annular displacement (TMAD) at the midpoint was significantly negatively
      correlated with LSglobal (r=-0.871, P<0.001). The 2D TMAD technique of measuring
      MAD was feasible and practically approachable for rapidly evaluating the left
      ventricular longitudinal global and segmental systolic functions of patients with
      HCM.

PMID- 24926327
TI  - Effect of Cordyceps sinensis and Tripterygium wilfordii polyglycosidium on
      podocytes in rats with diabetic nephropathy.
AB  - The aim of the present study was to investigate the effects of Cordyceps sinensis
      (CS) and Tripterygium wilfordii polyglycosidium (TWP) on podocytes in rats with
      diabetic nephropathy (DN). DN rat models were established and divided randomly
      into normal control (group A), DN (group B), CS (group C), TWP (group D) and CS
      and TWP groups (group E). After 12 weeks, levels of 24-h urinary protein, blood
      urea nitrogen (BUN), serum creatinine (SCR), white blood cells, blood glucose
      (GLU), aspartate aminotransferase, alanine aminotransferase and kidney weight
      (KW)/body weight (BW) were determined. Renal pathological changes were evaluated
      using hematoxylin and eosin staining, whereas the structural changes in the
      podocytes were observed under a transmission electron microscope. The expression
      levels of nephrin and podocin were evaluated using immunofluorescence staining.
      Compared with group A, the SCR and BUN levels in group B were higher (P<0.05) and
      the GLU, KW/BW and the 24-h urine protein were markedly higher (P<0.01).
      Moreover, incidences of glomerular disorders, chronic tubulointerstitial damage
      and glomerular podocyte lesions in groups B, C, D and E were observed, compared
      with group A. The high cortical expression of nephrin and podocin protein
      decreased. Compared with group B, the KW/BW and 24-h urinary protein level in
      groups C, D and E were lower (P<0.01). The glomeruli, tubules and podocytes
      exhibited pathomorphological improvements and the nephrin and podocin protein
      expression levels were higher in the nephridial tissue. A decrease in KW/BW and
      the 24-h urinary protein level, as well as improvements in glomerular disorder,
      chronic tubulointerstitial damage and glomerular podocyte lesions, were observed
      in groups C, D and E. Therefore, the results demonstrated that CS and TWP
      exhibited a protective effect on the podocytes of rats with DN. Moreover, CS
      combined with TWP increased this protective effect.

PMID- 24926328
TI  - Cajan leaf combined with bone marrow-derived mesenchymal stem cells for the
      treatment of osteonecrosis of the femoral head.
AB  - The aim of the present study was to observe the curative effect of traditional
      Chinese cajan leaves, combined with administration of bone marrow-derived
      mesenchymal stem cells (BMSCs), on osteonecrosis of the femoral head (ONFH) in
      rats and to investigate the underlying mechanisms. A total of 40 rat ONFH models
      were established through liquid nitrogen freezing and were subsequently divided
      into groups: A, control; B, treated with cajan leaf; C, treated with BMSCs and D,
      treated with cajan leaf combined with BMSCs. Samples were obtained 30 days
      following treatment, and immunohistochemical staining of vascular endothelial
      growth factor (VEGF) and image analysis were performed. Chondrocytes and vascular
      endothelial cells were stained as a result of immunohistochemical staining and
      group D exhibited markedly deeper staining, and a significantly larger number of
      stained cells, compared with group A. Thus, in the present study, cajan leaf
      combined with BMSCs was shown to promote VEGF expression and improve ONFH repair.

PMID- 24926329
TI  - Krukenberg tumor in a pregnant patient with severe preeclampsia.
AB  - Krukenberg tumors accompanied by gestational hypertension are rare and have a
      poor patient prognosis. A gravida 1, para 0 patient was submitted to Tianjin
      Medical University General Hospital (Tianjin, China) at 32 weeks gestation with
      symptoms of nausea, vomiting and hypertension. Diagnosis from the gastroscopic
      biopsy was of a gastric ulcer. A unilateral ovarian mass was identified with B
      scan ultrasonography and magnetic resonance imaging, but was confirmed
      pathologically as a bilateral Krukenberg tumor. Positron emission tomography
      computed tomography revealed a high radioactive uptake in the lesser curvature
      wall of the stomach, and postoperative pathology revealed poorly differentiated
      adenocarcinoma of the stomach. As Krukenberg tumors are difficult to diagnose,
      exhibit fast progression and have a poor clinical outcome, developing a greater
      understanding of Krukenberg tumors is crucial. Imaging manifestations combined
      with serological examination may aid in early detection, which may lead to
      improved patient management.

PMID- 24926330
TI  - Resolvin E1 reduces hepatic fibrosis in mice with Schistosoma japonicum
      infection.
AB  - The aim of this study was to investigate whether resolvin E1 (RvE1) protects
      against hepatic fibrosis in a murine model of liver fibrosis induced by
      Schistosoma japonicum infection. A total of 30 pathogen-free Kunming mice were
      randomly and equally divided into three groups: Control (uninfected, untreated),
      model (infected, untreated) and RvE1 intervention (infected, RvE1-treated; 100 ng
      daily). The mice were infected with Schistosoma japonicum by inoculating the
      abdominal skin with 20+/-2 cercariae to induce models of liver fibrosis. The area
      and numbers of the granulomas in the livers were assessed through histopathology
      after 70 days of treatment. The levels of tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma were evaluated in the serum by enzyme-linked immunosorbent
      assay (ELISA). The expression levels of TNF-alpha were detected in the hepatic
      tissue by reverse transcription-polymerase chain reaction and western blot
      analysis. The activity levels of alanine aminotransferase and aspartate
      aminotransferase were determined in the serum by ELISA. The expression levels of
      laminin (LN), hyaluronic acid (HA), procollagen type III (PC-III) and type IV
      collagen (IV-C) were detected in the serum by radioimmunoassays. The results
      revealed that the mean area of the granulomas was smaller in the RvE1
      intervention group compared with that in the model group. Following RvE1
      treatment, the serum levels of TNF-alpha were lower than those in the model
      group, while the serum levels of IFN-gamma were higher compared with those in the
      model group. The expression levels of TNF-alpha were lower in the hepatic tissue
      following RvE1 treatment compared with those in the model group. The indicators
      of liver fibrosis, the levels of LN, HA, PC-III and IV-C in the serum, were lower
      following RvE1 treatment than those in the model group. In conclusion, RvE1
      treatment may reduce the growth of granulomas, thereby slowing the process of
      hepatic fibrosis, and this effect may be the result of anti-inflammatory and
      immune system adjustment.

PMID- 24926331
TI  - Antagonistic effect of protein extracts from Streptococcus sanguinis on
      pathogenic bacteria and fungi of the oral cavity.
AB  - An antibacterial substance from Streptococcus sanguinis (S. sanguinis) is known
      to have an inhibitory effect on putative periodontal pathogens, but its
      inhibitory effect on pathogens of oral candidiasis is unknown. In this study,
      intracellular and exocrine proteins were extracted from S. sanguinis. The
      antagonistic effect of the protein extracts on Prevotella intermedia (P.
      intermedia) and Porphyromonas gingivalis (P. gingivalis) was detected by a well
      plate technique, and the effects of the protein extracts on biofilms formed by
      these bacteria were evaluated by confocal laser scanning microscopy. The
      antagonistic effect of the protein extracts on pathogenic fungi was investigated
      using Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis). The
      growth curves of C. albicans and C. tropicalis were determined from ultraviolet
      absorption measurements, their morphological changes following treatment were
      observed by optical microscopy and scanning electron microscopy, and the effects
      of the protein extracts on the thickness of their biofilms and the distribution
      of dead/live bacteria within the biofilms were detected by confocal laser
      scanning microscopy. The results showed significant inhibitory effects of the
      intracellular proteins extracted from S. sanguinis on pathogenic bacteria (P.
      intermedia and P. gingivalis), fungi (C. albicans and C. tropicalis) and the
      biofilms formed by them. Furthermore, the growth curves and morphology of C.
      albicans and C. tropicalis were altered following treatment with the
      intracellular proteins, resulting in disc-like depressions in the surfaces of the
      fungal spores and mycelia. By contrast, the exocrine proteins demonstrated no
      significant inhibitory effect on the pathogenic bacteria, fungi and the biofilms
      formed by them. Thus, it may be concluded that intracellular proteins of S.
      sanguinis have antibacterial activity and exert an antagonistic effect on certain
      pathogenic bacteria and fungi of the oral cavity.

PMID- 24926332
TI  - Analysis of multiple factors involved in acute progressive cerebral infarction
      and extra- and intracranial arterial lesions.
AB  - In order to identify the potential factors involved in the development of acute
      progressive cerebral infarction (PCI), the association between potential risk
      factors and extra- and intracranial arterial lesions was investigated. A total of
      608 patients underwent cerebral angiography to analyze the morphological
      characteristics between the PCI and NPCI groups. In addition, data from numerous
      cases of extra- and intracranial arterial lesions were collected and compared
      with the control groups, and the associations between the severity of arterial
      lesions and the potential influential factors were analyzed. In the blood vessels
      responsible for cerebral infarction, various degrees of atherosclerotic plaques
      and stenosis were observed. Age, high-density lipoprotein (HDL) levels,
      glycosylated hemoglobin and blood pressure affected the degrees of hardening,
      plaques and stenosis. Analysis of cerebral artery stenosis revealed that age,
      diabetes mellitus and plasma fibrinogen were risk factors for cerebral artery
      stenosis, while the HDL/low density lipoprotein ratio was a protective factor.
      Therefore, the results of the present study indicate that the lesions of blood
      vessels are a major pathological change in PCI and multiple factors are involved
      in the pathogenesis.

PMID- 24926333
TI  - Prognostic value of brain natriuretic peptide in patients with heart failure and
      reserved left ventricular systolic function.
AB  - Brain natriuretic peptide (BNP) is used as a prognostic biomarker for patients
      with heart failure (HF) in clinical practice, however, the correlation between
      BNP levels and the prognosis of HF in patients with reserved left ventricular
      systolic function (RLVSF) is not clear. Thus, the aim of the present study was to
      evaluate the added value of BNP in the prognosis of HF patients with RLVSF.
      Inpatients with cardiovascular disease (mean age, 65.7 years; male, 790; female,
      625) admitted to the Division of Cardiology at Jinshan Hospital of Fudan
      University (Shanghai, China) between June 2006 and December 2009 underwent follow
      up examinations. Plasma BNP levels were analyzed and measurements of the left
      ventricular ejection fraction (LVEF) were performed by echocardiography.
      Evaluations of the patients with HF were performed according to the New York
      Heart Association (NYHA) classification system. The duration of the follow-up
      period ranged between 21 and 63 months (average duration, 35.8 months) and key
      events included cardiovascular mortality, readmission due to cardiovascular
      disease or mortality due to other reasons. Survival times decreased with
      increasing BNP levels in all the follow-up patients (Spearman's rho, -0.1877;
      P<0.0001). Among the 1,415 patients, 1,312 underwent echocardiographic detection.
      A total of 395 patients with NYHA classes II-IV and a LVEF >=45% were selected.
      The incidence of compound endpoint events was significantly higher in the
      patients that had BNP levels of >100 pg/ml when compared with the patients that
      had BNP levels of <=100 pg/ml (37.07 vs. 23.93%; relative risk, 1.55);
      consequently the survival times were significantly reduced (P=0.0039). A negative
      correlation was identified between the BNP levels and the survival times in these
      patients (Spearman's rho, -0.1738; P=0.0005). These results indicated that the
      levels of BNP may be used to predict the prognosis of patients with
      cardiovascular disease. The prognoses of patients with higher BNP levels were
      worse compared with the patients with lower BNP levels. Furthermore, significant
      correlations were confirmed in the HF patients with RLVSF.

PMID- 24926334
TI  - Salvia miltiorrhiza extracts protect against retinal injury in a rat glaucoma
      model.
AB  - Glaucoma is a serious progressive degenerative disorder of the eye that leads to
      the continuous loss of retinal ganglion cells. Traditional Chinese medicine
      provides an important source for new drug screening and identification. The
      present study used Salvia miltiorrhiza (Danshen) extracts to examine the
      potential neuroprotective effects for the eye in a rat model of experimental
      glaucoma. The results of the study indicated that Salvia miltiorrhiza extracts
      were unable to prevent intraocular pressure increase in the laser-induced
      glaucoma model, but the treatment did reduce cell loss during glaucoma
      progression. Therefore, the results provide the basis for the development of a
      novel therapeutic agent that exhibits neuroprotective effects against glaucoma.
      In the future, further studies are required to purify the extracts and determine
      the effective bioactive components of Salvia miltiorrhiza.

PMID- 24926335
TI  - Pseudomonas aeruginosa inhibits the growth of pathogenic fungi: In vitro and in
      vivo studies.
AB  - The aim of the present study was to investigate the inhibitory effect of
      Pseudomonas aeruginosa (PA) on pathogenic fungi, including Candida albicans (CA),
      Candida tropicalis (CT), Candida glabrata (CG), Candida parapsilosis (CP) and
      Candida krusei (CK), in vitro and in vivo. In total, 24 PA strains were collected
      from clinical specimens and identified by Gram staining, oxidase production and
      the API 20NE system. Cross-streak, disk diffusion and co-culture methods were
      used to observe the inhibitory effect of PA. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was used to analyze differences in the
      bacterial proteins of PA. A blood infection model in mice was used to evaluate
      the effect of PA on fungi in vivo. The in vitro and in vivo results demonstrated
      that a number of PA isolates exhibited a marked inhibitory effect on pathogenic
      fungi, including CA, CT, CP, CG and CK, while other PA strains exhibited no
      effect. Therefore, PA exhibits an inhibitory effect on pathogenic fungi and this
      activity may be important in the treatment of patients. It was hypothesized that
      PA secretes various types of proteins to suppress the growth of fungal filaments,
      which subsequently inhibits pathogenic fungi.

PMID- 24926336
TI  - Malignant lymphoma of the ureter: A case report and literature review.
AB  - A 38-year-old male was admitted to Renji Hospital (Shanghai, China) with the
      major complaint of back pain due to left hydronephrosis. Imaging analysis
      revealed an area of nodular soft-tissue density in the left ureteral wall. The
      patient's left kidney was non-functional. Thus, a left nephroureterectomy was
      performed for the purpose of pathological diagnosis, and histopathological
      examination revealed follicular lymphoma. The patient received R-CHOP
      chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and
      prednisolone) every three weeks. Following six courses of chemotherapy, positron
      emission tomography-computed tomography revealed that the patient was in complete
      remission. From this case we showed that in cases where a partial ureteral
      stenosis with ureteral wall thickening was observed by imaging analysis, further
      histological examination of tissue samples should be assigned as soon as
      possible.

PMID- 24926337
TI  - A novel animal model of osteonecrosis of the femoral head induced using a
      magnetic resonance imaging-guided argon-helium cryotherapy system.
AB  - The aim of the present study was to establish a novel animal model of
      osteonecrosis of the femoral head (ONFH) using a magnetic resonance imaging (MRI)
      guided argon-helium cryotherapy system. A total of 48 rabbits were used to
      generate the ONFH models. In group I, the left femoral head of the rabbits
      received two cycles of argon-helium freezing-thawing under MRI guidance, while in
      group II, the right femoral head of each rabbit received only one cycle of argon
      helium freezing-thawing. X-ray and histological examinations were performed. The
      percentages of lacunae in the femoral heads of group I at weeks 4, 8 and 12
      following surgery (49.75+/-3.17, 62.06+/-4.12 and 48.25+/-2.76%, respectively)
      were higher than those in group II (39.13+/-4.48, 50.69+/-3.84 and 37.50+/-3.86%,
      respectively). In addition, the percentage of empty lacunae in group I was 62.06%
      at week 8 following surgery. Therefore, an animal model of ONFH was successfully
      established using an argon-helium cryotherapy system. The percentage of empty
      lacunae in group I was higher than that in group II at weeks 4, 8 and 12 after
      surgery.

PMID- 24926338
TI  - Electroacupuncture attenuates cervical spinal cord injury following cerebral
      ischemia/reperfusion in stroke-prone renovascular hypertensive rats.
AB  - Cerebral ischemia induces injury, not only in the ischemic core and surrounding
      penumbra tissues, but also in remote areas such as the cervical spinal cord. The
      aim of the present study was to determine the effects of electroacupuncture (EA)
      on cervical spinal cord injury following cerebral ischemia/reperfusion in stroke
      prone renovascular hypertensive (RHRSP) rats. The results demonstrated that
      neuronal loss, which was assayed by Nissl staining in the cervical spinal cords
      of RHRSP rats subjected to transient middle cerebral artery occlusion (MCAO), was
      markedly decreased by EA stimulation at the GV20 (Baihui) and GV14 (Dazhui)
      acupoints compared with that in rats undergoing sham stimulation. Quantitative
      polymerase chain reaction and western blot analysis demonstrated that EA
      stimulation blocked the MCAO-induced elevated protein expression levels of glial
      fibrillary acidic protein and amyloid precursor protein in the cervical spinal
      cord at days 24 and 48. To further investigate the mechanism underlying the
      neuroprotective role of EA stimulation, the protein expression levels of Nogo-A
      and Nogo-66 receptor-1 (NgR1), two key regulatory molecules for neurite growth,
      were recorded in each group. The results revealed that EA stimulation reduced the
      MCAO-induced elevation of Nogo-A and NgR1 protein levels at day 14 and 28 in
      RHRSP rats. Therefore, the results demonstrated that EA reduced cervical spinal
      cord injury following cerebral ischemia in RHRSP rats, indicating that EA has the
      potential to be developed as a therapeutic treatment agent for cervical spinal
      cord injury following stroke.

PMID- 24926339
TI  - Osteogenesis imperfecta type I: A case report.
AB  - A 15-year-old male patient was admitted to hospital having experienced repeated
      fractures over the previous three years, predominantly due to falling down or
      overexertion. The clinical signs and radiological features, such as recurrent
      fractures, blue sclera and low bone mineral density (BMD) level, all led to the
      diagnosis of a mild form of osteogenesis imperfecta (OI) type I. The patient
      began treatment with a regular intake of calcium (1,000 mg/day), an adequate
      intake of vitamin D (800 U/day) and intravenous pamidronate (60 mg). Following
      four months of treatment, the symptoms and quality of life of the patient
      improved. This patient appears to be a rare case of OI type I.

PMID- 24926340
TI  - BIIB021, an Hsp90 inhibitor, effectively kills a myelodysplastic syndrome cell
      line via the activation of caspases and inhibition of PI3K/Akt and NF-kappaB
      pathway proteins.
AB  - The novel orally available inhibitor of the molecular chaperone heat shock
      protein 90 (Hsp90), BIIB021, induces the apoptosis of various types of tumor cell
      in vitro and in vivo. However, the effects and mechanisms of this agent on
      myelodysplastic syndrome (MDS) cell lines remain unknown. The aim of this study
      was to investigate the effects of BIIB021 on SKM-1 cells (a MDS cell line) and
      examine its mechanisms of action. The results showed that BIIB021 inhibited the
      growth of SKM-1 cells effectively in vitro. The treatment of SKM-1 cells with
      BIIB021 resulted in the inhibition of cell growth through G0/G1-phase cell cycle
      arrest and induced apoptosis by activating caspase-3, -8 and -9. Furthermore,
      this study also demonstrated that the mechanisms of apoptosis in SKM-1 cells were
      associated with the suppression of the phosphatidylinositide 3-kinase/Akt and
      nuclear factor-kappaB signaling pathways. Therefore, the findings indicate a
      novel approach for the treatment of high-risk MDS.

PMID- 24926341
TI  - Septic shock due to community-acquired Pseudomonas aeruginosa necrotizing
      fasciitis: A case report and literature review.
AB  - Necrotizing fasciitis is a rare but fatal infection, characterized by the rapid
      progression of necrosis of the fascia, skin, soft tissue and muscle. The most
      common bacteria associated with necrotizing fasciitis is group A streptococcus,
      although other pathogens have also been implicated. In the present study, a case
      of community-acquired necrotizing fasciitis, complicated with septic shock and
      multiple organ dysfunction syndromes due to Pseudomonas aeruginosa, is presented.
      Despite intensive medical treatment, the condition of the patient deteriorated
      rapidly and the patient subsequently succumbed to multiple organ failure. In view
      of the rapid progression and high mortality rate of this disease, early surgery,
      as well as novel therapeutic approaches for septic shock are required to improve
      the outcome for patients.

PMID- 24926342
TI  - Feasibility of using a dual-promoter recombinant baculovirus vector to coexpress
      EGFP and GDNF in mammalian cells.
AB  - Vectors that are capable of coexpressing two or more exogenous genes for in vitro
      and in vivo gene delivery are being increasingly studied. The aim of the present
      study was to explore the feasibility of using the pFastBacTM Dual vector, under
      the control of two cytomegalovirus (CMV) promoters with opposite directions, to
      coexpress enhanced green fluorescent protein (EGFP) and glial cell line-derived
      neurotrophic factor (GDNF) in the same mammalian cell. In the study, two
      promoters in the pFastBac Dual vector were replaced with CMV-EGFP and CMV-GDNF,
      whose directions were consistent with the initial directions. The pFastBac Dual
      CMV-EGFP-CMV-GDNF plasmid was constructed and then transfected into human
      embryonic kidney (HEK) 293T cells. The recombinant virus, Bac Dual-CMV-EGFP-CMV
      GDNF, was generated with the Bac-to-Bac Baculovirus Expression system and used to
      transduce HeLa cells. Immunofluorescence was applied to examine the coexpression
      of EGFP and GDNF in transfected or transduced mammalian cells, while western blot
      analysis was used to confirm the expression of GDNF in transduced HeLa cells. The
      recombinant plasmid was constructed and the recombinant baculovirus was
      successfully generated. Immunofluorescence observations demonstrated that EGFP
      and GDNF were simultaneously expressed in the same transfected HEK 293T cell and
      in a single transduced HeLa cell. Western blot analysis revealed that GDNF was
      expressed accurately in the transduced cells. Therefore, the pFastBac Dual vector
      is an efficient gene transfer vector that is able to coexpress two target
      proteins in mammalian cells and serve as a platform for combining reporter or/and
      therapy genes used in molecular imaging and dual-gene therapy. Thus, the current
      study presents a new coexpression strategy for dual-gene delivery in vitro and in
      vivo.

PMID- 24926343
TI  - Estrogen preserves split renal function in a chronic complete unilateral ureteral
      obstruction animal model.
AB  - Estrogen may help to preserve renal function in chronic kidney disease. This
      study examined whether estrogen administration or deprivation affected the split
      renal function in rats subjected to chronic unilateral ureteral obstruction
      (UUO). Fifteen adult female Sprague-Dawley rats were randomly divided into three
      groups. Low- and high-estrogen groups were modeled by female castration or
      estrogen intraperitoneal injection, respectively, and the rats in the normal
      estrogen group were untreated. Intermittent split renal function [glomerular
      filtration rate (GFR)] examination was performed on rats on days 2, 6 and 16
      after UUO surgery via single-photon emission computed tomography (SPECT/CT).
      Routine hematoxylin and eosin (H&E) staining, immunohistochemistry, pathology
      examination and electron microscopy were performed to compare the histological
      differences. Low-, normal- and high-estrogen groups were successfully established
      (P<0.001). In the acute stage, the GFR of the contralateral healthy kidney showed
      a greater compensatory rise in the normal- and high-estrogen groups than in the
      low-estrogen group (P<0.05). In the chronic stage, the GFR of the obstructed
      kidney continued to decrease with the GFR of the high-estrogen group being
      significantly better preserved than that of the low-estrogen group (P<0.05). The
      GFR of the contralateral kidney compensated to the greatest extent in the high
      estrogen group (P=0.01), and the total GFR was significantly superior (P<0.05).
      Routine H&E examination showed significant histological changes following
      surgery. The low-estrogen group had significant renal interstitial fibrosis
      compared with the normal- and high-estrogen groups (P<0.05), as observed by
      immunohistochemical (IHC) examination of transforming growth factor-beta (TGF
      beta) and alpha-smooth muscle actin (alpha-SMA). Electron-microscopic (EM)
      examination also differentiated between groups. In conclusion, estrogen
      administration and deprivation significantly affected renal function. Estrogen
      may preserve the split renal function (GFR) in rats with chronic UUO.

PMID- 24926344
TI  - Optimal treatment of multivessel complex coronary artery disease.
AB  - The aim of the present study was to investigate major cardiac events and the
      similarities and differences of medical costs among patients with multivessel
      complex coronary artery disease (MCCAD) during the three-year follow-up. The
      MCCAD patients had undergone single complete revascularization (CR), fractionated
      revascularization (FR) or partial revascularization (PR) and the present study
      aimed to screen the optimal treatment program. A total of 2,309 MCCAD patients
      who had been treated at a single center in the last decade, among which 1,020
      cases underwent single CR, 856 cases successively underwent FR and 433 cases only
      underwent PR, were followed-up for three years. Major cardiac events, including
      all-cause mortality, myocardial infarction, severe heart failure,
      rehospitalization and revascularization (coronary artery bypass grafting and
      coronary stent reimplantation), were set as the end points. In addition, the
      three-year medical costs associated with heart disease were analyzed. The three
      year cardiac event rate in the CR group (17%) was significantly lower compared
      with the other two groups and the average three-year medical costs in the CR
      group (62,100 RMB) were significantly lower than those in the other two groups.
      Therefore, under permissive conditions, single CR is the optimal and most
      economical treatment strategy for patients with MCCAD.

PMID- 24926345
TI  - Correlation between estrogen receptor beta expression and the curative effect of
      endocrine therapy in breast cancer patients.
AB  - The aim of the present study was to investigate the association between the
      expression levels of estrogen receptor (ER)beta and the curative effect of
      endocrine therapy in breast cancer patients. Cancer tissues were collected from
      583 breast cancer patients between January 2000 and December 2010 and used for
      analysis. ERbeta expression levels were determined using immunohistochemical
      staining. The Kaplan-Meier method was used for survival analysis and the log-rank
      test was conducted for difference analysis between survival times. In addition,
      Cox multivariate analysis was performed to analyze prognostic factors for breast
      cancer. In the immunohistochemical staining assay, a positive ERbeta expression
      rate of <10% was defined as ERbeta low expression, while >10% was defined as
      ERbeta high expression. In patients expressing low levels of ERbeta, the median
      tumor-free survival time of the patients who received endocrine therapy was
      significantly higher compared with that of the patients who did not receive
      endocrine therapy. By contrast, in patients with high ERbeta expression levels,
      there was no significant difference in the median tumor-free survival time
      between the patients who received endocrine therapy and those who did not. In
      addition, compared with ERbeta low expression patients, ERbeta high expression
      patients had a significantly lower median tumor-free survival time. Furthermore,
      ERbeta expression, human epidermal growth factor receptor 2 expression, tumor
      size, lymph node metastasis, postoperative chemotherapy, radiotherapy and
      endocrine therapy were identified to be independent prognostic factors for breast
      cancer. Therefore, high ERbeta expression in breast cancer indicates poor
      prognosis for endocrine therapy.

PMID- 24926346
TI  - Evaluating the diagnostic value of vWF:Ag, D-D and FDP in patients with acute
      cerebral infarction using ROC curves.
AB  - Cerebral infarction is usually associated with arteriosclerosis, vascular
      endothelial cell injury and blood flow through the vascular system. The
      diagnostic value of markers, including von Willebrand factor antigen (vWF:Ag), D
      dimer (D-D) and fibrinogen/fibrin degradation product (FDP), have not been
      studied in patients with acute cerebral infarction. Thus, the aim of the present
      study was to use receiver operating characteristic (ROC) curves to evaluate the
      diagnostic significance of vWF:Ag, D-D and FDP in 94 cases of acute cerebral
      infarction. The results revealed that vWF:Ag and D-D concentrations were
      significantly higher in acute cerebral infarction patients as compared with the
      normal controls (P<0.01), whereas no statistically significant difference in FDP
      was observed between the groups (P>0.01). Plasma vWF:Ag and D-D concentrations
      significantly correlated with the National Institute of Health Stroke Scale
      (NIHSS) scores (r=0.625 and 0.582, respectively; P<0.01). In addition, the vWF:Ag
      concentration significantly correlated with the D-D concentration (r=0.320;
      P<0.01), whereas FDP concentration did not correlate with D-D or vWF:Ag
      concentrations or the NIHSS scores (r=0.172, 0.188 and 0.065, respectively;
      P>0.05). The area under the ROC curve using vWF:Ag as a diagnostic marker in
      patients with acute cerebral infarction was 0.900, while for D-D the area was
      0.795 and for FDP the area was 0.465. Logistic regression analysis revealed that
      the odds ratios of vWF:Ag and D-D were 16.727 and 2.324, respectively, which were
      statistically significant (P<0.001 and 0.023, respectively). These results
      indicated that using vWF:Ag as a diagnostic marker is likely to significantly
      improve the sensitivity of diagnosing patients with acute cerebral infarction.
      The diagnostic value of vWF:Ag concentration was significantly higher compared
      with D-D and FDP levels.

PMID- 24926347
TI  - Expression of ERCC1, TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal
      squamous cell carcinoma: A hierarchical clustering analysis.
AB  - The aim of the present study was to investigate the correlation between the
      expression levels of excision repair cross complementing 1 (ERCC1), thymidylate
      synthase (TYMS), class III beta-tubulin (TUBB3), ribonucleoside-diphosphate
      reductase (RRM1) and topoisomerase IIalpha (TOP2A) with the clinical
      characteristics of patients with esophageal squamous cell carcinoma (ESCC). A
      total of 29 ESCC tissue samples were collected from patients that had not
      previously received systematic treatment. The expression levels of ERCC1, TYMS,
      TUBB3, RRM1 and TOP2A were determined using a microarray technique, while
      Spearman's rank correlation analysis was used to determine the strength of the
      correlations between the expression levels of the biomarkers and the pathogenesis
      of esophageal cancer. High expression levels of TYMS and TOP2A were observed in
      24% of the samples and high expression levels of TUBB3 and RRM1 were identified
      in 7% of the samples. Hierarchical clustering analysis of these biomarkers
      enabled the samples to be grouped. Group 1 patients exhibited low expression
      levels of TYMS, RRM1 and TOP2A and high expression of ERCC1 and TUBB3, while
      group 2 samples had low expression levels of ERCC1 and TUBB3 and high expression
      levels of TYMS, RRM1 and TOP2A. Analysis using Fisher's exact test demonstrated a
      statistically significant difference in the severity of carcinoma invasion
      between the two groups (P<0.05), however, no significant differences were
      identified with regard to the clinical stage or lymphatic metastasis (P>0.05).
      Therefore, hierarchical clustering analysis indicated that the expression levels
      of ERCC1, TYMS, TUBB3, RRM1 and TOP2A were closely associated with the clinical
      characteristics of patients with ESCC.

PMID- 24926348
TI  - Novel, fast and efficient image-based 3D modeling method and its application in
      fracture risk evaluation.
AB  - Constructing models based on computed tomography images for finite element
      analysis (FEA) is challenging under pathological conditions. In the present
      study, an innovative method was introduced that uses Siemens syngo(r) 3D software
      for processing models and Mimics software for further modeling. Compared with the
      slice-by-slice traditional manual margin discrimination, the new 3D modeling
      method utilizes automatic tissue margin determination and 3D cutting using syngo
      software. The modeling morphologies of the two methods were similar; however, the
      3D modeling method was 8-10 times faster than the traditional method,
      particularly in cases with osteoporosis and osteophytes. A comparative FEA study
      of the lumbar spines of young and elderly patients, on the basis of the models
      constructed by the 3D modeling method, showed peak stress elevation in the
      vertebrae of elderly patients. Stress distribution was homogeneous in the entire
      vertebrae of young individuals. By contrast, stress redistribution in the
      vertebrae of the elderly was concentrated in the anterior cortex of the
      vertebrae, which explains the high fracture risk mechanism in elderly
      individuals. In summary, the new 3D modeling method is highly efficient, accurate
      and faster than traditional methods. The method also allows reliable FEA in
      pathological cases with osteoporosis and osteophytes.

PMID- 24926349
TI  - Effects of differenta mitomycin C concentrations on laser-assisted subepithelial
      keratectomy.
AB  - The aim of the present study was to determine the effect of different
      concentrations of mitomycin C (MMC) administered intraoperatively during laser
      assisted subepithelial keratectomy (LASEK) surgery. A total of 261 patients (496
      eyes) were randomly divided into two groups: 0.04% MMC treatment group consisting
      of 133 patients (245 eyes) and the 0.02% MMC treatment group consisting of 128
      patients (251 eyes). The MMC solutions were dropped intraoperatively onto the
      ablation region and the duration was dependent on the preoperative refractive
      power of the patient's cornea: <=-3.00 diopters (D), 30 sec; between -3.25 D and 
      6.00 D, 60 sec; between -6.25 D and -9.00 D, 90 sec and >=-9.25 D, 110 sec.
      Postoperative observations included haze formation, visual acuity, changes in
      refractive power, corneal endothelial cell density and incidence of
      complications. The one year postoperative incidence of haze differed
      significantly between the groups (P<0.05). The one week and one year comparisons
      of postoperative visual acuity also differed significantly between the groups
      (P<0.05). Postoperative changes in corneal refractive power at one, six and 12
      months following surgery significantly differed between the groups (P<0.05). No
      statistically significant difference was identified between the density of
      corneal endothelial cells prior to surgery and the density at one, six and 12
      months following surgery (P>0.05). Thus, the intraoperative application of 0.04%
      MMC solution effectively inhibited haze formation and markedly improved the
      efficacy of LASEK surgery, when compared with that of 0.02% MMC.

PMID- 24926350
TI  - Intraocular lens implantation for patients with coloboma of the iris.
AB  - The aim of this study was to analyze the techniques for intraocular lens (IOL)
      implantation in patients with coloboma of the iris. A retrospective cohort study
      was used to analyze the degree of iris coloboma and the characteristics of the
      crystalline lens in 56 patients with iris coloboma. The patients with a lesser
      degree of coloboma of the iris and an intact lens capsule were treated by iris
      suture and IOL implantation into the posterior chamber. Patients with an iris
      coloboma confined to one quadrant, severe iris atrophy and significant lens
      capsule coloboma were treated with an annular suture at the edge of the pupil and
      IOL implantation into the anterior chamber. Patients with a greater degree of
      iris coloboma and an intact lens capsule were treated with an artificial iris and
      IOL implantation. The patients were followed up for between five months and five
      years after surgery. Data relating to vision, photophobia, IOL location,
      postoperative complications and treatment were also obtained at follow-up. The
      vision of the patients was improved to varying degrees following the surgery,
      with the exception of those with amblyopia or serious corneal scars. The
      photophobia of the patients had also improved. The patients' levels of
      satisfaction and comfort were deemed to be satisfactory. Early postoperative
      complications included hyphema, increased intraocular pressure and uveitis.
      However, serious complications such as corneal decompensation and IOL dislocation
      were not observed. Various techniques for IOL implantation were selected based on
      the degree of iris and lens capsule coloboma; these techniques were capable of
      improving the vision and photophobia of the patients.

PMID- 24926351
TI  - Amelioration of insulin resistance in rat cells by Astragalus polysaccharides and
      associated mechanisms.
AB  - The aim of this study was to investigate the function of Astragalus
      polysaccharides (APS) in ameliorating insulin resistance (IR) in rat cells and to
      elucidate the associated mechanisms. Fully differentiated, induced 3T3-L1 rat
      adipocytes were divided into a control group and three intervention groups. The
      intervention groups were incubated in media containing 0.001, 0.1 and 10 MUg/MUl
      APS, respectively, for 48 h. Following treatment, levels of interleukin (IL)-6
      and adiponectin secreted by the cultured adipocytes were measured using enzyme
      linked immunosorbent assay. Levels of adiponectin secreted by the 3T3-L1
      adipocytes in the moderate-concentration intervention group were significantly
      increased compared with those in the control group (P<0.05), whereas levels of
      adiponectin secreted by the 3T3-L1 adipocytes in the low- and high-concentration
      intervention groups were decreased compared with those in the control group
      (P<0.05 and P>0.05, respectively). Levels of IL-6 secreted by the 3T3-L1
      adipocytes in the three intervention groups were lower than those in the control
      group (P>0.05, P<0.05 and P<0.05 for the low- moderate- and high-concentration
      intervention groups, respectively), and demonstrated APS dose-dependence. The
      results indicate that APS are capable of increasing adiponectin secretion and
      reducing IL-6 secretion by 3T3-L1 rat adipocytes in a dose-dependent manner.
      These findings may identify a potential mechanism for ameliorating IR using APS.

PMID- 24926352
TI  - Effects of the combination of methylprednisolone with aminoguanidine on
      functional recovery in rats following spinal cord injury.
AB  - Methylprednisolone (MP), a synthetic glucocorticoid, has been widely used as a
      standard therapeutic agent for the treatment of spinal cord injury (SCI). The
      combination of MP and other pharmacological agents aimed at enhancing functional
      recovery is desirable as the beneficial effects of MP are controversial, due to a
      variety of side-effects. Aminoguanidine (AG), a small water-soluble compound, is
      potentially useful in the treatment of acute SCI. The aim of the present study
      was to determine the effects of MP and AG, administered in combination, following
      SCI in adult rats. In rats with SCI, the combination therapy group treated with
      AG (75 mg/kg) and MP (0.75 mg/kg) exhibited significantly reduced levels of
      cytokine expression and cell apoptosis compared with those in the control group.
      In addition, the data demonstrated that the combination therapy significantly
      enhanced the recovery of limb function. These data clearly suggest that treatment
      with a combination of MP and AG represents a promising strategy of clinically
      applicable pharmacological therapy for the rapid initiation of neuroprotection
      following SCI.

PMID- 24926353
TI  - Resveratrol reverses multidrug resistance in human breast cancer doxorubicin
      resistant cells.
AB  - Although its mechanisms remain unidentified, resveratrol (trans-3,4',5
      trihydroxystilbene; RES), which is an active, low molecular-weight compound,
      possesses a unique antitumor function and is capable of enhancing the
      cytotoxicity of doxorubicin (DOX) within solid tumor cells. RES is hypothesized
      to exert these effects by reversing the multidrug resistance (MDR) of the cancer
      cells in response to chemotherapeutic agents. The aim of the present study was to
      investigate the reversal effect of RES on MDR in human breast cancer DOX
      resistant (MCF-7/DOX) cells and investigate the underlying mechanisms of RES. The
      results demonstrated that RES inhibited the proliferation of MCF-7/DOX and MCF-7
      cells in a dose-dependent manner. Moreover, RES enhanced the cytotoxicity of DOX
      on MCF-7/DOX cells and the reversal index of RES treatment was demonstrated to be
      significantly higher when compared with that of the group without RES treatment.
      In addition, RES was observed to reverse the MDR of the MCF-7/DOX cells and
      elevate the concentration of DOX in the MCF-7/DOX cells. Furthermore, RES was
      identified to significantly downregulate the MDR-1 gene and P-glycoprotein
      expression levels. Reversing MDR, via the downregulation of MDR-1 expression, was
      concluded to be a mechanism of RES, which enables the unique antitumor function
      of this polypeptide. Therefore, the present study indicated that RES may be a
      novel MDR reversal agent for the treatment of breast cancer.

PMID- 24926354
TI  - Plasma orexin-A and ghrelin levels in patients with chronic obstructive pulmonary
      disease: Interaction with nutritional status and body composition.
AB  - Orexin-A and ghrelin are two important polypeptides that stimulate food intake,
      however, there is a lack of sufficient information concerning their plasma levels
      in patients with chronic obstructive pulmonary disease (COPD). The aim of the
      present study was to investigate the association between plasma orexin-A and
      ghrelin levels with food consumption and body composition in patients with stable
      phase COPD. In total, 40 patients (age, 44-80 years; male, 31; female 9) who were
      in the stable phase of COPD were included in the study. Blood samples for plasma
      orexin-A and ghrelin analysis were collected after 8-12 h of fasting; certain
      anthropometric measurements were obtained and a 24-h dietary recall was recorded.
      The mean plasma orexin-A levels in the male and female patients were 1.3+/-0.37
      and 1.4+/-0.13 ng/ml, respectively, while the mean plasma ghrelin levels were
      25.9+/-7.31 and 27.3+/-8.54 ng/ml, respectively. No significant correlation was
      observed between the body mass index and plasma orexin-A and ghrelin levels or
      between the plasma ghrelin levels and dietary nutrient intake (P>0.05). The
      plasma orexin-A levels were demonstrated to be higher in patients with a higher
      dietary total fibre intake (r=0.303, P=0.022). A similar correlation was observed
      between plasma orexin-A levels and dietary intake of soluble (r=0.033, P=0.029)
      and insoluble (r=0.335, P=0.024) fibre, as well as between the daily consumption
      of calcium and the levels of plasma orexin-A (r=0.065, P=0.046). Therefore, the
      results of the present study indicated that a positive correlation existed
      between dietary nutrient intake and plasma orexin-A levels in patients with COPD.

PMID- 24926355
TI  - Effects of ulinastatin administered at different time points on the pathological
      morphologies of the lung tissues of rats with hyperthermia.
AB  - Hyperthermia not only directly induces cell injury of body tissues, but also
      causes the body to release large amounts of inflammatory mediators and cells with
      extensive biological activities to induce a systemic inflammatory response and
      immune dysfunction. Thus, hyperthermia causes systemic inflammatory response
      syndrome, aggravating injuries to various organs. This study aimed to observe the
      effects of ulinastatin (UTI) administered at different time points on the
      cellular morphologies of the lung tissues of rats with systemic hyperthermia. A
      total of 40 male Sprague Dawley rats were randomly divided into five groups: The
      normal control group (C group), the hyperthermia group without medication (H
      group), the hyperthermia and UTI pre-treatment group (HU group), the group
      treated with UTI at 1 h after hyperthermia (HU1 group), and the group treated
      with UTI at 2 h after hyperthermia (HU2 group). The systemic hyperthermia rat
      model was established in a heating chamber with a biological oxygen supply. For
      the HU, HU1 and HU2 groups, UTI (5*104 U/kg) was administered at different time
      points. For the C and H groups, an equivalent volume of normal saline was
      administered. During heating, the respiratory frequency and rectal temperature
      were measured and recorded once every 30 min. After 2.5 h of heating, the wet/dry
      weight (W/D) ratio of the lung tissues of the rats was measured. Additionally,
      the cellular morphologies of the lung tissues were observed under light and
      electron microscopes. The respiratory frequencies and lung tissue W/D ratios of
      the rats in the various hyperthermia groups were significantly higher than those
      of the rats in the C group (all P<0.05). The respiratory frequencies and lung
      tissue W/D values of the HU and HU1 groups were significantly lower than those of
      the H group (all P<0.05). Under the light microscope, the bronchial surrounding
      tissues of the HU and HU1 groups were loose, and the majority of the pulmonary
      alveolar structures were normal; the H and HU2 groups presented a number of
      changes, including pulmonary interstitial hyperemia, alveolar epithelial swelling
      and emphysema. Under the electron microscope, it was observed in the type II
      epithelial cells of the pulmonary alveoli of the H group that the mitochondria
      were swollen, the cell ridges were shortened, the microvilli were thin and
      increased, and the alveolar wall was thickened. Also, an increased number of
      infiltrating neutrophils were visible. In addition, the type II epithelial cells
      of the HU2 group also presented these changes to different extents and the
      changes in the HU and HU1 groups were the mildest. These results indicate that
      the early application of UTI relieves edema and the extent of cell injury of the
      lung tissue in rats with systemic hyperthermia.

PMID- 24926356
TI  - Effects of dexmedetomidine on the deformability of erythrocytes in vitro and in
      anesthesia.
AB  - The current study aimed to evaluate the impact of clinically relevant
      concentrations of dexmedetomidine on the deformability of erythrocytes in vitro
      and the effects of dexmedetomidine on the deformability of erythrocytes in
      patients undergoing laparoscopic cholecystectomy. Erythrocyte suspensions of
      different concentrations were divided into six groups: Control (group C); low,
      medium and high concentrations of dexmedetomidine (groups DL, DM and DH,
      respectively); yohimbine alone (group Y) and yohimbine mixed with dexmedetomidine
      (group YD). The suspensions were incubated in a thermostatic shaking incubator
      (50 rpm, 37 degrees C) for 60 min. The nitric oxide (NO) concentrations and
      endothelial nitric oxide synthase (eNOS) activities of red blood cells and the
      erythrocyte deformability index (EI) were then measured. Patients (n=40)
      scheduled for laparoscopic cholecystectomy were randomly divided into a
      dexmedetomidine group (group A) and a control group (group B). The induction and
      maintenance of anesthesia in the two groups was identical. The EI and hematocrit
      (Hct) were assayed prior to anesthesia (T0) and following the surgery (T1). In
      the in vitro assay, the EI, the activity of eNOS and the NO concentration of the
      erythrocytes were significantly higher in groups DL, DM, DH and YD than in group
      C (P<0.05). In addition, the EI, the eNOS activity and NO concentration of the
      erythrocytes were higher in group DM than in group YD (P<0.05). In the patients,
      the EI value at T1 (0.90+/-0.04) was higher than at T0 (0.81+/-0.06) in group B
      (P<0.05). No statistically significant difference between the EI values at T0 and
      T1 was identified in group A (P>0.05). Dexmedetomidine treatment is able to
      improve the deformability of erythrocytes in vitro and in anesthesia. The
      improvement of erythrocyte deformability by dexmedetomidine may be partially
      associated with adrenergic receptors through activation of eNOS to enhance the
      concentration of NO in red blood cells.

PMID- 24926357
TI  - 3,3'-Diindolylmethane inhibits the invasion and metastasis of nasopharyngeal
      carcinoma cells in vitro and in vivo by regulation of epithelial mesenchymal
      transition.
AB  - Nasopharyngeal carcinoma (NPC) is characterized by silent progression and
      atypical early symptoms. Early metastasis to the neck lymph nodes is common.
      However, conventional chemoradiotherapy is limited and unable to effectively
      control cervical lymph node metastasis of NPC. In addition, toxicities caused by
      chemoradiotherapy often induce damage to normal tissues and organs. Thus, the aim
      of this study was to investigate the ability of 3,3'-diindolylmethane (DIM) to
      inhibit the invasion and metastasis of NPC cells in vitro and in vivo. The
      migration and invasive abilities of the 5-8F human NPC cell line were detected
      using a Transwell assay. Lymph node metastasis in nude mice was observed
      following the implantation of xenograft tumors for 8 weeks. In addition, western
      blot analysis was used to detect the expression levels of epithelial mesenchymal
      transition (EMT)-associated key proteins in NPC cells treated with DIM in vitro
      and in vivo. The results demonstrated that DIM effectively inhibited the
      migration and invasion of NPC cells in vitro and the effect was concentration
      dependent. In addition, DIM significantly delayed and reduced the occurrence of
      lymph node metastasis in the animal model. The expression levels of a number of
      key proteins associated with EMT were affected by DIM treatment. In the animal
      model, there were no signs of toxicity in the vital organs, including the heart,
      liver and kidney, of animals fed a diet containing DIM. Therefore, the results of
      the present study indicate that DIM affects the expression levels of a number of
      EMT-associated key proteins and induces the inhibition of invasion and metastasis
      of NPC cells in vitro and in vivo.

PMID- 24926358
TI  - Inhibitory effect of sodium houttuyfonate on synovial proliferation in vitro in
      cells from a patient with rheumatoid arthritis.
AB  - The aim of the present study was to investigate the inhibitory effect of sodium
      houttuyfonate (SH) on synovial cell proliferation in vitro. Primary cells were
      obtained from the synovial tissue of a patient with rheumatoid arthritis (RA).
      The cells were divided into five treatment groups as follows: the control group
      (group 1), 25 MUg/ml SH-treated group (group 2), 50 MUg/ml SH-treated group
      (group 3), 100 MUg/ml SH-treated group (group 4) and the 200 MUg/ml SH-treated
      group (group 5). Following seven days of treatment, the proliferation rate of the
      synovial cells was then detected using an MTT assay. The expression level of
      proliferative synovial cells markedly decreased in the SH-treated groups in a
      dose-dependent manner compared with the control group. In conclusion, the present
      study demonstrated that SH was able to inhibit the proliferation of synovial
      cells obtained from a patient with RA. These results provide a potential
      theoretical basis for the development of a safe and effective treatment against
      RA in the future.

PMID- 24926359
TI  - Combined electrocardiography, coronary angiography and magnetic resonance imaging
      for the diagnosis of viral myocarditis: A case report.
AB  - Endomyocardial biopsy is the gold standard for diagnosing viral myocarditis.
      However, this method is rarely used as it is more invasive, less sensitive and
      has a higher incidence of complications than other methods. With recent
      developments in myocarditis research, cardiovascular nuclear magnetic resonance
      imaging has been demonstrated to have a marked advantage over endomyocardial
      biopsy, specifically regarding the differential diagnosis of acute coronary
      syndrome, as it is noninvasive, repeatable, highly sensitive and highly specific
      for diagnosing myocarditis. Myocardial edema is characteristic of myocardial
      inflammation, myocardial necrosis and myocardial fibrosis. T2-weighted nuclear
      magnetic resonance imaging sensitively detects myocardial tissue edema and
      additional imaging parameters contribute to the diagnosis of myocarditis.
      Therefore, combining these methods with the current sophisticated
      electrocardiogram and coronary angiography examination methods may facilitate the
      rapid and accurate assessment of viral myocarditis. A 44-year-old male patient
      with symptoms of dyspnea and shortness of breath accompanied by dizziness,
      through electrocardiography, coronary angiography and magnetic resonance imaging,
      was diagnosed viral myocarditis.

PMID- 24926360
TI  - Urantide improves atherosclerosis by controlling C-reactive protein, monocyte
      chemotactic protein-1 and transforming growth factor-beta expression in rats.
AB  - The aim of the present study was to investigate the effects of urantide on the
      expression status of C-reactive protein (CRP) and the inflammatory cytokines
      monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-beta in
      the aortas of rats with atherosclerosis (AS), and to identify its underlying
      mechanisms. The effects of urantide in a rat model of AS and in cultured rat
      vascular smooth muscle cells (VSMCs) were analyzed via hematoxylin and eosin
      staining, immunohistochemical staining and ELISA. The results in vivo
      demonstrated that urantide downregulated the expression of inflammatory mediators
      CRP and MCP-1 and upregulated the expression of TGF-beta. The results in vitro
      indicated that urantide inhibited the proliferation of VSMCs. In addition,
      urantide reduced the expression of CRP and downregulated the secretion of TGF
      beta in the culture supernatant. In conclusion, urantide ameliorated the arterial
      inflammatory damage that was observed in the AS rat model at the cell and tissue
      levels by controlling the expression of CRP and the inflammatory cytokines MCP-1
      and TGF-beta. Therefore, urantide may be a potential agent for the complementary
      treatment of AS.

PMID- 24926362
TI  - Effect of erythropoietin loading chitosan-tripolyphosphate nanoparticles on an
      IgA nephropathy rat model.
AB  - The aim of the present study was to investigate the effect of erythropoietin
      (EPO) loading chitosan-tripolyphosphate (CS-TPP) nanoparticles on an
      immunoglobulin A nephropathy (IgAN) rat model. CS-TPP nanoparticles were produced
      from CS and TPP and EPO was loaded by mixing with the nanoparticles. The IgAN rat
      models were randomly divided into three groups: the CS-TPP-EPO group, CS-TPP
      group and EPO group. Hemoglobin (Hb), blood urea nitrogen (BUN) and creatinine
      (Cr) levels were measured in each group using a Biochemical Analyzer (Hitachi,
      Tokyo, Japan). The average size of nanoparticles was 485+/-12 nm and the
      encapsulation efficiency of EPO was 78.45%. The EPO release curve in CS-TPP-EPO
      nanoparticles exhibited a biphasic distribution in vitro. The levels of BUN and
      Cr in the CS-TPP-EPO group were significantly lower compared with the control
      group (P<0.05); however, the level of Hb in the CS-TPP-EPO group was higher
      compared with the other groups (P<0.05). The changes in Hb, BUN and Cr in the CS
      TPP-EPO group were maintained for less than one week following the end of the
      treatment with CS-TPP-EPO nanoparticles. In conclusion, the CS-TPP-EPO
      nanoparticles had a lower toxicity compared with EPO and CS-TPP treatment.
      Furthermore, CS-TPP-EPO may improve the therapeutic effect in the IgAN model.
      This suggests that CS-TPP-EPO nanoparticles may be a potential therapeutic drug
      for the treatment of patients with IgAN.

PMID- 24926361
TI  - Curcumin suppresses tumor necrosis factor-alpha-induced matrix metalloproteinase
      2 expression and activity in rat vascular smooth muscle cells via the NF-kappaB
      pathway.
AB  - The aim of the present study was to investigate the inhibitory effect of curcumin
      on tumor necrosis factor (TNF)-alpha-induced cell migration and matrix
      metalloproteinase (MMP)-2 expression and activity in rat vascular smooth muscle
      cells (VSMCs), in order to identify whether the effects are mediated by the
      nuclear factor (NF)-kappaB signaling pathway. The VSMCs cells were pretreated
      with curcumin prior to stimulation with TNF-alpha. Reverse transcription
      polymerase chain reaction and western blot analysis were used to determine the
      MMP-2 mRNA and protein expression levels in TNF-alpha-stimulated VSMCs. Activity
      levels of MMP-2 were measured using a gelatin zymography assay. Intracellular
      reactive oxygen species (ROS) generation was also analyzed. Curcumin was found to
      suppress the TNF-alpha-stimulated migration of VSMCs. In addition, curcumin
      inhibited the TNF-alpha-induced induction of MMP-2 activity and expression.
      Curcumin also decreased ROS generation in TNF-alpha-stimulated VSMCs. Signal
      transduction experiments indicated that TNF-alpha-induced MMP-2 expression in
      VSMCs was partly reversed with the application of an NF-kappaB inhibitor (BAY11
      7082). In addition, western blot analysis revealed that curcumin reduced NF
      kappaB p65 protein expression in TNF-alpha-stimulated VSMCs at the concentration
      of 20 and 40 MUM. Therefore, these observations indicated that curcumin
      suppressed TNF-alpha-stimulated VSMC migration and partially prevented TNF-alpha
      induced MMP-2 expression and activity in VSMCs via the NF-kappaB pathway.

PMID- 24926363
TI  - Calcineurin inhibitors may be a reasonable alternative to cyclophosphamide in the
      induction treatment of active lupus nephritis: A systematic review and meta
      analysis.
AB  - Although the accepted standard of care during the induction treatment of active
      lupus nephritis (LN) has been cyclophosphamide (CYC), recent trials suggest that
      calcineurin inhibitors (CNIs), which include cyclosporine A (CsA) and tacrolimus
      (TAC), may be just as, or even more, effective and less toxic than CYC. A
      systematic review and meta-analysis were performed to evaluate the clinical
      effects of CNIs on active LN compared with those of CYC. In the present study,
      clinical trials that compared CNIs with CYC in the induction therapy of active LN
      were searched in the Cochrane Library, Ovid and PubMed databases. The clinical
      data on renal remission and side-effects were collected and analyzed. The
      relative risk (RR) and 95% confidence intervals (CIs) were calculated. As a
      result, six controlled trials involving 265 patients were included in the meta
      analysis, four of which compared TAC (treatment group) with CYC (control group),
      and the other two compared CsA (treatment group) with CYC (control group). CNIs
      were superior to CYC for higher complete remission (RR=1.56, 95% CI 1.14-2.15,
      Z=2.74, P=0.006) and better overall response/total remission (RR=1.23, 95% CI
      1.07-1.42, Z=2.87, P=0.004) and had fewer side-effects. Among the CNIs, TAC
      demonstrated more favorable results than CsA. Therefore, it was concluded that
      CNIs may be a reasonable alternative to CYC in the induction treatment of active
      LN. However, large-scale, multicenter, well-designed clinical trials should be
      adopted to further confirm this conclusion.

PMID- 24926364
TI  - Study of the correlation between serum ferritin levels and the aggregation of
      metabolic disorders in non-diabetic elderly patients.
AB  - The present study aimed to explore the correlation between serum ferritin (SF)
      levels and the aggregation of metabolic disorders in non-diabetic elderly
      patients. A total of 2,600 patients were enrolled in the study. Various
      parameters, including blood pressure (BP), height, weight, lipid profiles, blood
      glucose (BG), body mass index (BMI), fasting insulin (FINS), serum uric acid
      (SUA), the urinary albumin/creatinine ratio (UACR) and SF levels were measured. A
      homeostatic model was used to evaluate insulin resistance (HOMA-IR) and beta-cell
      function (HOMA-beta). The quantitative insulin sensitivity check index (QUICKI)
      and disposition index (DI) were calculated. The QUICKI and DI decreased
      significantly and other parameters increased significantly when the number of
      metabolic disorders increased. Patients with high triglycerides (TG), high total
      cholesterol (TC), high SUA and obesity demonstrated higher SF levels than those
      with normal TG, normal TC, normal SUA and normal weight, respectively (P<0.01).
      Male patients with metabolic disorders (high TG, high TC, high BP, high SUA and
      obesity) had higher SF levels than female patients with the corresponding
      disorders (P<0.01). BG, FINS, BMI, TC, TG, SUA, HOMA-IR and HOMA-beta were
      positively correlated with SF, while DI and QUICKI were negatively correlated
      with SF (P<0.01). Stepwise regression analysis showed that HOMA-IR, BMI, TC, TG
      and SUA were risk factors for elevated SF levels. In conclusion, the SF levels in
      non-diabetic, elderly individuals with metabolic disorders may be significantly
      related to the clustering of the metabolic disorders. Dyslipidemia, obesity,
      disorders of purine metabolism and insulin resistance may be important risk
      factors for higher SF levels in the elderly.

PMID- 24926365
TI  - SB-273005, an antagonist of alphavbeta3 integrin, reduces the production of Th2
      cells and cytokine IL-10 in pregnant mice.
AB  - Pregnancy is associated with complex immunoreactions. In the present study, the
      effect of SB-273005, an antagonist of alphavbeta3 integrin, on the alterations of
      T helper (Th) cells and their derived cytokines that occur during pregnancy was
      investigated in mice. Five non-pregnant mice were used as a negative control.
      Mice were impregnated by co-housing females and males at a ratio of 2:1 overnight
      and pregnancy was confirmed by the appearance of vaginal plugs the following
      morning. Day 1 (D1) pregnant mice were randomly divided into two groups (n=20)
      and were administered either dimethylsulfoxide (mock treatment) or SB-273005 (3
      mg/kg) by gavage at D3, D4 and D5. At D8, the levels of Th1 and Th2 cells and
      interleukin (IL)-2 and IL-10 in the spleen and peripheral blood were determined
      using flow cytometry and enzyme-linked immunosorbent assay. Pregnancy
      significantly increased the ratio of Th2:Th1 cells in the spleen compared with
      that in non-pregnant mice (P<0.01). However, this increase was significantly
      reduced by SB-273005 (P<0.001). Furthermore, whilst pregnancy decreased Th1 cell
      produced IL-2 levels and increased Th2 cell-derived IL-10 levels, SB-273005
      reversed both processes (P<0.05 for IL-2; P<0.01 for IL-10). The results from the
      present study demonstrated that pregnancy induces changes in the spleen,
      including a reduction of IL-2 and an increase in IL-10 production by Th1 and Th2
      cells, respectively, as well as an upregulation of the Th2:Th1 ratio in the
      spleen. These immunological changes are reversed by SB-273005, indicating an
      important role for alphavbeta3 integrin in mediating these immunological
      alterations.

PMID- 24926366
TI  - Effects of ulinastatin on cerebral oxygen metabolism and CRP levels in patients
      with severe traumatic brain injury.
AB  - The aim of the present study was to investigate the effects of ulinastatin on
      cerebral oxygen metabolism and C-reactive protein (CRP) levels in patients with
      severe traumatic brain injury (sTBI). A total of 92 patients with sTBI, admitted
      to the First Affiliated Hospital of Xinxiang Medical University (Xinxiang,
      China), were randomly divided into control and observation groups. The control
      group received conventional therapy plus a placebo (0.9% sodium chloride), while
      the observation group were administered conventional therapy plus 200,000 units
      ulinastatin via intravenous injection twice a day for seven days. Arterial and
      jugular venous blood was collected for blood gas analysis. The jugular venous
      blood lactate (JVBL), jugular venous bulb oxygen saturation (SjvO2),
      arteriovenous oxygen content difference (AVDO2) and cerebral extraction of oxygen
      (CEO2) levels were measured on day 1, 3, 5 and 7, as well as the level of CRP in
      the peripheral blood. In the control group, the level of JVBL decreased as
      compared with the level at day 1, however, no statistically significant
      differences were observed (P>0.05). By contrast, the observation group exhibited
      a significant reduction in the level of JVBL (P<0.05), which was also
      significantly lower compared with the control group (P<0.05). Statistically
      significant differences were observed between the two groups with regard to
      SjvO2, AVDO2 and CEO2 on day 3, 5 and 7. The CRP levels in the two groups
      increased and peaked on day 3. However, the CRP level in the observation group
      significantly decreased on day 5 (35.27+/-15.18 mg/l) and day 7 (22.65+/-10.48
      mg/l), which was lower compared with the control group (56.19+/-13.24 mg/l and
      47.36+/-15.73 mg/l, respectively); statistically significant differences were
      observed (P<0.05). Therefore, ulinastatin effectively improved cerebral oxygen
      metabolism and reduced the CRP level in patients with sTBI.

PMID- 24926367
TI  - Treatment effect of Bushen Huayu extract on postmenopausal osteoporosis in vivo.
AB  - Bushen Huayu extract (BSHY), a traditional Chinese medicine, has been
      demonstrated to treat postmenopausal osteoporosis, however, the underlying
      mechanism remains to be fully elucidated. The aim of the present study was to
      investigate the therapeutic effect of BSHY and the mechanisms underlying this
      effect in an in vivo postmenopausal osteoporosis animal model. A total of 1 g
      BSHY containing 7.12 MUg icariin was prepared. Low-dose BSHY (BSHY-L; 11.1 g/kg),
      medium-dose BSHY (BSHY-M; 22.2 g/kg) and high-dose BSHY (BSHY-H; 44.4 g/kg) was
      administered to oophorectomized rats using intragastric infusion. Estradiol (E2),
      interleukin-6 (IL-6) and serum alkaline phosphatase (ALP) levels, as well as bone
      density, were determined. It was found that the levels of serum ALP in the BSHY
      L, BSHY-M and BSHY-H groups (197.75+/-41.74, 166.63+/-44.83 and 165.63+/-44.90
      IU/l, respectively) were significantly decreased compared with the model group
      (299.13+/-45.79 IU/l; P<0.05), whilst the levels of E2 (16.89+/-1.71, 17.95+/
      1.40 and 18.34+/-1.43 pg/ml, respectively) increased compared with the model
      group (14.54+/-1.61; P<0.05). In addition, the levels of IL-6 decreased in the
      BSHY-L, BSHY-M and BSHY-H groups (91.85+/-14.81, 82.99+/-15.65 and 80.54+/-14.61
      pg/ml, respectively) compared with the model group (105.93+/-16.50 pg/ml;
      P<0.05). Furthermore, it was demonstrated that BSHY increased the bone density in
      the BSHY-L, BSHY-M and BSHY-H groups (0.20+/-0.014, 0.22+/-0.016 and 0.22+/-0.017
      g/cm2, respectively) compared with the model group (0.19+/-0.011 g/cm2; P<0.05).
      BSHY was also found to increase the number of osteoblasts in the BSHY-L, BSHY-M
      and BSHY-H groups (25.38+/-2.17, 29.25+/-2.12 and 30.00+/-2.39, respectively),
      compared with in the model group (14.75+/-2.38; P<0.05), and decrease the number
      of osteoclasts in the BSHY-L, BSHY-M and BSHY-H groups (4.00+/-1.85, 4.25+/-1.39
      and 5.75+/-1.49, respectively) compared with 9.50+/-1.60 observed in the model
      group (P<0.05). These results suggest that BSHY is a potential therapeutic drug
      for the treatment of osteoporosis in vivo. Furthermore, these results suggest
      that the mechanism by which BSHY decreases the serum levels of IL-6 may be by
      regulating E2.

PMID- 24926368
TI  - Inhibition of SENP5 suppresses cell growth and promotes apoptosis in osteosarcoma
      cells.
AB  - SUMOylation is a dynamic and reversible process. Several SUMO-specific proteases
      (SENPs) that remove SUMO from substrates have been shown to be amplified in a
      subset of cancers. SENP5 is required for cell division, as well as maintaining
      mitochondrial morphology and function. SENP5 has been reported to be
      predominantly localized to the cytoplasm of oral squamous cell carcinoma (OSCC)
      and is associated with the differentiation of OSCC. Western blot was used to
      detect the protein expression of SENP5 in osteosarcoma cells and tissue.
      Lentivirus-mediated siRNA was used to silence the expression of SENP5. Cell cycle
      distribution was determined by FACS analysis. The present study showed that SENP5
      is overexpressed in osteosarcoma cells. In addition, lentivirus-mediated small
      interfering RNA (siRNA) of SENP5 significantly inhibited cell growth and induced
      apoptosis in osteosarcoma cells. SENP5 inhibition suppressed the growth and
      colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2.
      Silencing the expression of SENP5 in serum-starved U2OS and Saos-2 cells induced
      an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression.
      These observations indicate that SENP5 is required for cell growth and apoptosis
      and may therefore be a promising drug target for antiosteosarcoma treatment.

PMID- 24926369
TI  - Bitterness intensity prediction of berberine hydrochloride using an electronic
      tongue and a GA-BP neural network.
AB  - The aim of this study was to predict the bitterness intensity of a drug using an
      electronic tongue (e-tongue). The model drug of berberine hydrochloride was used
      to establish a bitterness prediction model (BPM), based on the taste evaluation
      of bitterness intensity by a taste panel, the data provided by the e-tongue and a
      genetic algorithm-back-propagation neural network (GA-BP) modeling method. The
      modeling characteristics of the GA-BP were compared with those of multiple linear
      regression, partial least square regression and BP methods. The determination
      coefficient of the BPM was 0.99965+/-0.00004, the root mean square error of cross
      validation was 0.1398+/-0.0488 and the correlation coefficient of the cross
      validation between the true and predicted values was 0.9959+/-0.0027. The model
      is superior to the other three models based on these indicators. In conclusion,
      the model established in this study has a high fitting degree and may be used for
      the bitterness prediction modeling of berberine hydrochloride of different
      concentrations. The model also provides a reference for the generation of BPMs of
      other drugs. Additionally, the algorithm of the study is able to conduct a rapid
      and accurate quantitative analysis of the data provided by the e-tongue.

PMID- 24926370
TI  - Clinical significance of TLR3 and TLR4 in peripheral blood mononuclear cells from
      children with Henoch-Schonlein purpura nephritis.
AB  - The aim of the present study was to investigate the expression levels and
      clinical significance of Toll-like receptor (TLR) 3 and 4 in peripheral blood
      mononuclear cells (PBMCs) collected from children with Henoch-Schonlein purpura
      (HSP) nephritis. The randomized controlled trial was conducted between August
      2011 and March 2013, and 105 children with a clinical diagnosis of HSP were
      enrolled in the study. According to the 24-h urinary protein measurements and the
      presence of renal damage, the 105 cases were divided into groups A, B and C as
      follows: Group A, children with HSP but without renal damage; group B, children
      with HSP nephritis but without proteinuria; group C, children with HSP nephritis
      and proteinuria. A total of 30 healthy children were enrolled in the normal
      control group (group N). The primary endpoints were the detection of TLR3 and 4
      mRNA and protein expression levels in PBMCs by flow cytometry and quantitative
      polymerase chain reaction. The mRNA and protein expression levels of TLR4 in the
      PBMCs were significantly higher in groups A, B and C when compared with group N.
      In addition, the mRNA and protein expression levels of TLR4 in group C were much
      higher when compared with groups A and B. A positive correlation was identified
      between TLR4 protein expression and 24-h urinary protein levels in group C. The
      expression levels of TLR3 did not significantly differ among the groups. Protein
      and mRNA expression levels of TLR4 in PBMCs significantly increased and exhibited
      a positive correlation with urinary protein excretion. These results indicate
      that aberrant activation of TLR4 may be relevant to the development of HSP
      nephritis.

PMID- 24926371
TI  - Activation of the TLR1/2 pathway induces the shaping of the immune response
      status of peripheral blood leukocytes.
AB  - Toll-like receptors (TLRs) play an essential role in the activation and
      regulation of the innate and adaptive immune responses through the recognition of
      specific components of pathogens. TLR1/2 on the cell surface plays an important
      role in defending against Gram-positive bacteria. The aim of the present study
      was to examine the expressional variation of immunomodulatory molecules in
      peripheral blood leukocytes (PBLs) treated with the TLR1/2 agonist, Pam3Cys. The
      quantitative polymerase chain reaction result showed dramatically increased
      expression of immune-related factors treated with Pam3Cys. Antibody-chip assays
      confirmed that activation of TLR1/2 could induce secretion of four important
      immune factors [interleukin (IL)-6, IL-8, macrophage inflammatory protein-1alpha
      and interferon-beta). Western-blot analysis indicated the upregulation of three
      significant signal kinase proteins (phosphorylated signal transducer and
      activator of transcription 3, extracellular signal-related kinase and c-Jun N
      terminal kinase 2). The study demonstrated that there were numerous molecules
      involved in the immune response of PBLs stimulated by the TLR1/2 ligand. Our
      future studies will focus on the mechanisms of these molecules in the TLR1/2
      agonist-mediated immune response.

PMID- 24926372
TI  - Clinical analysis of pulmonary infection in hemodialysis patients.
AB  - The present study aimed to investigate the pathogen distribution and drug
      resistance of lung infections in hemodialysis to guide clinical empirical
      pharmacy. The clinical data of 116 hemodialysis patients with pulmonary infection
      were analyzed. The majority of the 82 pathogens isolated from the sputa of
      patients were Gram-negative bacteria (accounting for 71.95%). The results of the
      drug sensitivity test suggested that Gram-negative bacilli had low resistance
      rates to piperacillin and tazobactam, imipenem and amikacin, while Gram-positive
      cocci had a low resistance rate to vancomycin. All resistance rates of the
      pathogens to other common antimicrobials were >50%. The pathogens resulting in
      lung infections in hemodialysis patients were mainly Gram-negative bacteria and
      were significantly resistant to various antibacterials. Results of the this study
      demonstrate that pathological examination should be performed as early as
      possible and effective antimicrobial agents should be chosen according to drug
      sensitivity test results.

PMID- 24926373
TI  - Renal tuberculosis and iliopsoas abscess: Two case reports.
AB  - The urinary system is the second most commonly affected site of extrapulmonary
      tuberculosis (TB). Due to the diverse and atypical clinical manifestations of
      urinary TB, the disease is easy to misdiagnose. In the present study, two cases
      of renal TB are reported, which had completely different clinical manifestations.
      The first case is a female who presented with loin pain and fever. Purified
      protein derivative (PPD) and TB antibody tests were negative and computed
      tomography (CT) scans showed a low density focus in the right kidney with an
      iliopsoas abscess. The typical CT findings indicated renal tuberculosis. Anti-TB
      drugs were effective proved the diagnosis. The second case is a male who
      presented with intermittent gross hematuria. Acid-fast bacilli in urine and TB
      antibody tests were positive. CT scans revealed a low density focus in the
      unilateral kidney with a slight expansion of the pelvis, calices and ureter. The
      patients were treated with the anti-TB drugs and the clinical manifestations
      disappeared. The diagnosis of urinary TB is challenging in certain cases; when
      there is no response to the usual antibiotics in patients with fever or gross
      hematuria, TB should be suspected. CT is the mainstay for investigating possible
      urinary TB.

PMID- 24926374
TI  - Association between serum angiotensin-converting enzyme 2 levels and
      postoperative myocardial infarction following coronary artery bypass grafting.
AB  - Myocardial infarction (MI) is a predominant and severe complication in patients
      that undergo aortocoronary bypass surgery. Angiotensin-converting enzyme 2 (ACE2)
      activation is reportedly a protective mechanism in MI; therefore, in the present
      study, the association between serum ACE2 levels and postoperative MI following
      coronary artery bypass grafting (CABG) was investigated. Preoperative and
      postoperative serum ACE2 levels in 136 subjects undergoing CABG were observed and
      the serum ACE2 levels, 1 h post surgery, were divided into quartile categories.
      Following adjustment for age, gender, body mass index, hypertension, previous MI,
      current smoking status, hyperlipidemia, diabetes mellitus, Gensini score, aortic
      clamp time, number of grafts and pre-CABG medications; the risk of developing
      postoperative MI following CABG was observed to be significantly higher in the
      lowest serum ACE2 level quartile than when compared with the highest quartile
      (hazard ratio, 2.94; 95% confidence interval, 1.85-4.16; P=0.009). The subjects
      that exhibited a serum ACE2 level <=1.06 ng/ml showed significantly higher rates
      of postoperative MI, arrhythmia and reduced cardiac output in addition to
      increased instances of in-hospital mortality post CABG, compared with those
      exhibiting a serum ACE2 level >1.06 ng/ml. A significant negative correlation was
      observed between serum ACE2 and serum cardiac troponin I levels, however, no
      significant association was identified between the serum ACE2 level quartiles and
      the ACE2 gene polymorphisms. The present study indicated that a low serum ACE2
      level, 1 h post CABG was independently associated with an increased risk of
      postoperative MI. Thus, the serum ACE2 level may be a potential novel prognostic
      factor for postoperative MI following CABG.

PMID- 24926375
TI  - Efficacy and safety of a new robot-assisted stereotactic system for
      radiofrequency thermocoagulation in patients with temporal lobe epilepsy.
AB  - The aim of the present study was to evaluate the efficacy and safety of a newly
      developed robot-assisted frameless stereotactic system for deep electrode
      implantation and radiofrequency thermocoagulation (RFTC). Deep-electrode
      implantation was performed in the bilateral mesial temporal lobes of seven
      patients. Following the implantation of the deep electrodes through the monitored
      designed path, the epileptogenic zones were determined with the assistance of a
      robot system. Deep electrode electroencephalograms were recorded prior to and
      following RFTC. Treatment outcomes were evaluated by computed tomography scans
      and Engel classification criteria. The procedure was well tolerated by all
      patients with no patients suffered from severe permanent complications. After
      follow-ups for 34-62 months, four patients achieved Engel class I, including
      three patients with Ia classification, two patients were classified as Engel
      class IVa and one patient was classified as Engel class IVc. Therefore, robot
      assisted frameless stereotaxy for deep electrode implantation and RFTC is
      indicated to be a safe and effective method that may be used effectively in
      clinical practice.

PMID- 24926376
TI  - Immunomodulatory effects of Potentilla indica and Dendrophthoe pentandra on mice
      splenocytes and thymocytes.
AB  - Immunomodulators are agents that are able to stimulate or inhibit the immune
      response. The leaf extracts from Potentilla indica and Dendrophthoe pentandra
      were analyzed in vitro for immunomodulatory activity and an MTT colorimetric
      assay was conducted to determine the proliferation of mice splenocytes and
      thymocytes. A bromodeoxyuridine assay was performed to analyze DNA synthesis and
      the Trypan blue exclusion method was conducted to evaluate the changes in total
      cell population. The results indicated that treatment with P. indica and D.
      pentandra produced a time- and dose-dependent increase in cell viability and
      proliferation. Following 72 h of treatment with P. indica and D. pentandra,
      thymocyte proliferation was augmented by 18 and 41%, respectively and splenocyte
      proliferation increased by 35 and 42%, respectively, when compared with untreated
      cells. The present study demonstrated that these extracts may act as potential
      immunostimulants and, thus, represent an alternative source of immunomodulatory
      compounds for the treatment of human immune-mediated diseases.

PMID- 24926377
TI  - Effects of methylthiouracil on the proliferation and apoptosis of rat bone marrow
      stromal cells.
AB  - The aim of the present study was to investigate the effects of methylthiouracil
      (MTU) on the proliferation and apoptosis of rat bone marrow stromal cells
      (BMSCs). Rat BMSCs were isolated, cultured in vitro and treated with various
      concentrations of MTU. Cell growth curves were determined using the Cell Counting
      Kit-8 method and the effect of MTU on BMSCs in a logarithmic growth phase was
      observed. BMSC apoptosis following MTU treatment was detected by flow cytometry.
      The experimental results demonstrated that the proliferation-inhibition effect
      was gradually enhanced with increasing MTU concentrations and the extension of
      treatment time. Statistically significant differences were observed between the
      treatment and the control groups (P<0.05). In addition, the BMSC apoptosis rate
      gradually increased with increasing drug concentrations and treatment time
      extension; statistically significant differences were observed between the
      treatment and the control groups (P<0.05). Therefore, the results of the present
      study demonstrated that MTU inhibited the proliferation of BMSCs and promoted
      apoptosis, indicating the cytotoxic effects of MTU on BMSCs.

PMID- 24926378
TI  - Protective mechanism of Xuebijing injection against heat stroke in rats.
AB  - This study aimed to investigate the protective mechanism of Xuebijing injection
      (XBJ) against heat stroke (HS) in rats. Adult male Sprague Dawley rats were
      randomly divided into normal control (NC), normal saline-treated HS (NS-HS) and
      XBJ-treated HS (XBJ-HS) groups. At 47 and 57 min from the initiation of heat
      stress (42.5-43.5 degrees C), the plasma levels of certain cytokines [interleukin
      (IL)-1beta, IL-6 and tumor necrosis factor-alpha], biochemical indicators
      (creatinine, blood urea nitrogen, aspartate aminotransferase, alanine
      aminotransferase and alkaline phosphatase) and coagulation indicators (activated
      partial thromboplastin time, prothrombin time, fibrinogen degradation products
      and D-dimer) were detected, and microscopy of the liver tissue of the rats was
      conducted. At 47 and 57 min after the initiation of the heat stress, the levels
      of the cytokines, coagulation indicators and biochemical indicators in the NS-HS
      group were significantly higher than those in the NC group (P<0.05). In the NS-HS
      group, the levels of the aforementioned indices were significantly reduced
      compared with those in the NC and NS-HS groups (P<0.05). In the NS-HS group,
      serious liver cell congestion, nuclear swelling and central vein dilation were
      visible, along with the appearance of bubbles in the liver tissue. In the XBJ-HS
      group, only a small number of congestive liver cells were identified, with
      occasional nuclear swelling but no bubbles, which was similar to the observations
      in the NC group. Early intervention treatment of HS with XBJ is able to reduce
      the systemic inflammatory response and coagulation activity and decrease the
      tissue ischemia and injury degree, thus extending the survival time of rats with
      HS.

PMID- 24926379
TI  - Randomized controlled clinical trial of a combination therapy of vildagliptin
      plus an alpha-glucosidase inhibitor for patients with type II diabetes mellitus.
AB  - The aim of this study was to assess the efficacy of a combination therapy of
      vildagliptin plus an alpha-glucosidase inhibitor for patients with type II
      diabetes mellitus. Type II diabetic patients exhibiting poor glycemic control
      following alpha-glucosidase inhibitor treatment for at least two months were
      selected and randomly distributed into vildagliptin and placebo groups. The body
      weight, fasting blood glucose (FBG), postprandial glucose (PPG), glycated
      hemoglobin (HBA1c) and blood lipid levels and hepatorenal functions of the
      patients were determined before and 12 weeks after the trial. Following the
      trial, the FBG, PPG, HbA1c, cholesterol (CHOL) and triglyceride (TG) levels in
      the vildagliptin group were significantly decreased compared with the
      pretreatment levels (P<0.05), whereas only the PPG level in the placebo group
      decreased (P<0.05). The FBG, PPG and HbA1c levels in the vildagliptin group were
      markedly lower than those in the placebo group 12 weeks after the trial. A
      comparison of the body weights and hepatorenal functions before and after the
      trial or between groups did not show statistically significant differences. The
      combination therapy of vildagliptin plus an alpha-glucosidase inhibitor
      effectively reduced the FBG, PPG and HbA1c levels in patients without inducing
      weight gain or hepatorenal dysfunction. However, the therapy may have caused a
      reduction in the blood lipid levels.

PMID- 24926380
TI  - miR-375 inhibits the proliferation of gastric cancer cells by repressing ERBB2
      expression.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the
      expression of targeted genes in a post-transcriptional manner. Increasing
      evidence indicates that miRNAs play important roles in cancer pathogenesis,
      including apoptosis, proliferation and differentiation, as oncogenes or tumor
      suppressors. Previously, miR-375 was shown to be involved in human gastric
      cancer, however, the mechanism remains poorly understood. In the present study,
      miR-375 was shown to be downregulated in gastric cancer tissues, particularly
      human epidermal growth factor receptor 2 (ERBB2)-positive gastric cancer tissues.
      Identified by dual luciferase assays and western blot analysis, ERBB2 was
      demonstrated to be a target gene of miR-375. In addition, miR-375 overexpression
      suppressed the proliferation of human gastric cancer cells in vitro and the
      suppression effect was restored by ERBB2 overexpression. Thus, the results of the
      present study indicate that miR-375 is associated with human gastric
      carcinogenesis by targeting ERBB2. Therefore, miR-375 may be used as a potential
      clinical classification marker and therapeutic target for human gastric cancer.

PMID- 24926381
TI  - Resveratrol affects the expression of glutamate cysteine ligase in the kidneys of
      aged rats.
AB  - The aim of the present study was to evaluate the effect that a dietary intake of
      resveratrol (RSV) had on the expression of glutamate cysteine ligase (GCL) in the
      kidneys of aged rats. Young, middle-aged and aged rats were each randomly divided
      into two groups. The control groups were fed a controlled diet and the
      experimental groups received a controlled diet supplemented with RSV. GCL
      activity levels in the kidneys were determined. Protein content and relative gene
      expression levels of the two subunits of GCL were evaluated by western blot
      analysis and quantitative polymerase chain reaction, respectively. GCL activity
      levels significantly increased in the kidneys of aged rats fed the RSV
      supplemented diet. In addition, RSV markedly increased the protein content and
      relative mRNA expression levels of the GCL subunits in the kidneys of aged rats.
      These observations have important implications for the development of therapeutic
      agents for the kidneys that may enable the elderly population to combat oxidative
      stress.

PMID- 24926382
TI  - JWA regulates human esophageal squamous cell carcinoma and human esophageal cells
      through different mitogen-activated protein kinase signaling pathways.
AB  - The aim of the present study was to investigate whether the JWA gene regulates
      the proliferation, migration and invasion of human esophageal squamous cell
      carcinoma (ESCC) and normal human esophageal cell lines through mitogen-activated
      protein kinase (MAPK) signal transduction pathways. The role of JWA in
      proliferation, migration, invasion and apoptosis was investigated in the Eca109
      human ESCC and HET-1A normal human esophageal cell lines via transfection with
      JWA-small interfering (si)RNA. Western blot analysis was conducted to observe the
      effect of JWA on apoptosis and the regulatory effect of JWA on proliferation was
      determined using a thiazolyl blue tetrazolium bromide (MTT) assay. Cellular
      migration and invasion were analyzed via a Transwell assay. In addition, the
      expression levels of extracellular signal-regulated protein kinases 1 and 2
      (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK following JWA-siRNA
      transfection were detected by western blot analysis and compared with those of
      untreated cells. The downregulation of JWA protein decreased apoptosis and
      increased the proliferation, migration and invasion of the Eca109 and HET-1A cell
      lines. In the Eca109 cell line, the expression levels of phosphorylated (p)
      ERK1/2 and p-JNK, but not those of p-p38, decreased significantly in the JWA
      siRNA group compared with those in the control groups. However, in the HET-1A
      cell line, JWA-siRNA transfection significantly inhibited the expression of p-p38
      and demonstrated no effect on the expression levels of p-ERK1/2 and p-JNK. In
      conclusion, the JWA gene may regulate the ESCC and human esophageal cell lines
      through MAPK signaling pathways via different regulatory mechanisms.

PMID- 24926383
TI  - Combined application of alginate dressing and human granulocyte-macrophage colony
      stimulating factor promotes healing in refractory chronic skin ulcers.
AB  - The aim of the present study was to evaluate the clinical therapeutic effect of
      the combined application of alginate and recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF) on the healing of refractory chronic skin
      ulcers. A single center, three arm, randomized study was performed at Jinan
      Central Hospital (Jinan, Shandong, China). A total of 60 patients with refractory
      chronic skin ulcers, which persisted for >1 month, were enrolled and randomly
      assigned into one of the following three groups: alginate dressing/rhGM-CSF group
      (group A), rhGM-CSF only group (group B) and conventional (vaseline dressing)
      group (group C). The wound area rate was measured, granulation and color were
      observed and pain was evaluated. The data were summarized and statistical
      analysis was performed. The results demonstrated that group A exhibited a
      significantly faster wound healing rate and lower pain score compared with the
      other groups (P<0.01). In conclusion, the combined application of alginate
      dressing and rhGM-CSF for the treatment of refractory chronic skin ulcers
      demonstrated significant advantages. It promoted the growth of granulation
      tissue, accelerated re-epithelialization and also effectively reduced wound pain,
      and thus improved the quality of life for the patient. This suggests that the
      combined application of alginate and rhGM-CSF may be an effective therapeutic
      strategy for the clinical treatment of refractory chronic skin ulcers.

PMID- 24926385
TI  - Upregulated expression levels of ADAM10 and EGFR and downregulated expression
      levels of E-cadherin in hepatocellular carcinomas.

PMID- 24926384
TI  - Understanding the polypharmacological anticancer effects of Xiao Chai Hu Tang via
      a computational pharmacological model.
AB  - Xiao Chai Hu Tang (XCHT), a traditional herbal formula, is widely administered as
      a cancer treatment. However, the underlying molecular mechanisms of its
      anticancer effects are not fully understood. In the present study, a
      computational pharmacological model that combined chemical space mapping,
      molecular docking and network analysis was employed to predict which chemical
      compounds in XCHT are potential inhibitors of cancer-associated targets, and to
      establish a compound-target (C-T) network and compound-compound (C-C) association
      network. The identified compounds from XCHT demonstrated diversity in chemical
      space. Furthermore, they occupied regions of chemical space that were the same,
      or close to, those occupied by drug or drug-like compounds that are associated
      with cancer, according to the Therapeutic Targets Database. The analysis of the
      molecular docking and the C-T network demonstrated that the potential inhibitors
      possessed the properties of promiscuous drugs and combination therapies. The C-C
      network was classified into four clusters and the different clusters contained
      various multi-compound combinations that acted on different targets. The study
      indicated that XCHT has a polypharmacological role in treating cancer and the
      potential inhibitory components of XCHT require further investigation as
      potential therapeutic strategies for cancer patients.

PMID- 24926386
TI  - A novel on-chip three-dimensional micromachined calorimeter with fully enclosed
      and suspended thin-film chamber for thermal characterization of liquid samples.
AB  - A microfabricated calorimeter (MU-calorimeter) with an enclosed reaction chamber
      is presented. The 3D micromachined reaction chamber is capable of analyzing
      liquid samples with volume of 200 nl. The thin film low-stress silicon nitride
      membrane is used to reduce thermal mass of the calorimeter and increase the
      sensitivity of system. The MU-calorimeter has been designed to perform DC and AC
      calorimetry, thermal wave analysis, and differential scanning calorimetry. The MU
      calorimeter fabricated with an integrated heater and a temperature sensor on
      opposite sides of the reaction chamber allows to perform thermal diffusivity and
      specific heat measurements on liquid samples with same device. Measurement
      results for diffusivity and heat capacitance using time delay method and thermal
      wave analysis are presented. 

PMID- 24926387
TI  - Long-term microfluidic glucose and lactate monitoring in hepatic cell culture.
AB  - Monitoring cellular bioenergetic pathways provides the basis for a detailed
      understanding of the physiological state of a cell culture. Therefore, it is
      widely used as a tool amongst others in the field of in vitro toxicology. The
      resulting metabolic information allows for performing in vitro toxicology assays
      for assessing drug-induced toxicity. In this study, we demonstrate the value of a
      microsystem for the fully automated detection of drug-induced changes in cellular
      viability by continuous monitoring of the metabolic activity over several days.
      To this end, glucose consumption and lactate secretion of a hepatic tumor cell
      line were continuously measured using microfluidically addressed electrochemical
      sensors. Adapting enzyme-based electrochemical flat-plate sensors, originally
      designed for human whole-blood samples, to their use with cell culture medium
      supersedes the common manual and laborious colorimetric assays and off-line
      operated external measurement systems. The cells were exposed to different
      concentrations of the mitochondrial inhibitor rotenone and the cellular response
      was analyzed by detecting changes in the rates of the glucose and lactate
      metabolism. Thus, the system provides real-time information on drug-induced liver
      injury in vitro. 

PMID- 24926388
TI  - Enhanced electrohydrodynamic collapse of DNA due to dilute polymers.
AB  - We experimentally demonstrate that addition of small, charge-neutral polymers to
      a buffer solution can promote compression of dilute solutions of single
      electrophoresing DNA. This phenomenon contrasts with the observed extension of
      DNA during capillary electrophoresis in dilute solutions of high molecular weight
      polymers. We propose these discrepancies in micron-scale DNA configurations arise
      from different nano-scale DNA-polymer collision events, controlled by solute
      polymer properties. We build upon theories previously proposed for intermolecular
      DNA aggregation in polymer-free solutions to develop scaling theories that
      describe trends seen in our data for intramolecular DNA compaction in dilute
      polymer solutions. 

PMID- 24926389
TI  - Single cell kinase signaling assay using pinched flow coupled droplet
      microfluidics.
AB  - Droplet-based microfluidics has shown potential in high throughput single cell
      assays by encapsulating individual cells in water-in-oil emulsions. Ordering
      cells in a micro-channel is necessary to encapsulate individual cells into
      droplets further enhancing the assay efficiency. This is typically limited due to
      the difficulty of preparing high-density cell solutions and maintaining them
      without cell aggregation in long channels (>5 cm). In this study, we developed a
      short pinched flow channel (5 mm) to separate cell aggregates and to form a
      uniform cell distribution in a droplet-generating platform that encapsulated
      single cells with >55% encapsulation efficiency beating Poisson encapsulation
      statistics. Using this platform and commercially available Sox substrates (8
      hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a
      high throughput dynamic single cell signaling assay to measure the activity of
      receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface
      ligand binding. The phosphorylation of the substrates resulted in fluorescent
      emission, showing a sigmoidal increase over a 12 h period. The result exhibited a
      heterogeneous signaling rate in individual cells and showed various levels of
      drug resistance when treated with the tyrosine kinase inhibitor, gefitinib. 

PMID- 24926390
TI  - Microfluidic dielectrophoretic sorter using gel vertical electrodes.
AB  - We report the development and results of a two-step method for sorting cells and
      small particles in a microfluidic device. This approach uses a single
      microfluidic channel that has (1) a microfabricated sieve which efficiently
      focuses particles into a thin stream, followed by (2) a dielectrophoresis (DEP)
      section consisting of electrodes along the channel walls for efficient continuous
      sorting based on dielectric properties of the particles. For our demonstration,
      the device was constructed of polydimethylsiloxane, bonded to a glass surface,
      and conductive agarose gel electrodes. Gold traces were used to make electrical
      connections to the conductive gel. The device had several novel features that
      aided performance of the sorting. These included a sieving structure that
      performed continuous displacement of particles into a single stream within the
      microfluidic channel (improving the performance of downstream DEP, and avoiding
      the need for additional focusing flow inlets), and DEP electrodes that were the
      full height of the microfluidic walls ("vertical electrodes"), allowing for
      improved formation and control of electric field gradients in the microfluidic
      device. The device was used to sort polymer particles and HeLa cells,
      demonstrating that this unique combination provides improved capability for
      continuous DEP sorting of particles in a microfluidic device. 

PMID- 24926391
TI  - High-efficiency rare cell identification on a high-density self-assembled cell
      arrangement chip.
AB  - Detection of individual target cells among a large amount of blood cells is a
      major challenge in clinical diagnosis and laboratory protocols. Many researches
      show that two dimensional cells array technology can be incorporated into routine
      laboratory procedures for continuously and quantitatively measuring the dynamic
      behaviours of large number of living cells in parallel, while allowing other
      manipulations such as staining, rinsing, and even retrieval of targeted cells. In
      this study, we present a high-density cell self-assembly technology capable of
      quickly spreading over 300 000 cells to form a dense mono- to triple-layer cell
      arrangement in 5 min with minimal stacking of cells by the gentle incorporation
      of gravity and peripheral micro flow. With this self-assembled cell arrangement
      (SACA) chip technology, common fluorescent microscopy and immunofluorescence can
      be utilized for detecting and analyzing target cells after immuno-staining.
      Validated by experiments with real human peripheral blood samples, the SACA chip
      is suitable for detecting rare cells in blood samples with a ratio lower than
      1/100 000. The identified cells can be isolated and further cultured in-situ on a
      chip for follow-on research and analysis. Furthermore, this technology does not
      require external mechanical devices, such as pump and valves, which simplifies
      operation and reduces system complexity and cost. The SACA chip offers a high
      efficient, economical, yet simple scheme for identification and analysis of rare
      cells. Therefore, potentially SACA chip may provide a feasible and economical
      platform for rare cell detection in the clinic. 

PMID- 24926392
TI  - Paper-based colorimetric enzyme linked immunosorbent assay fabricated by laser
      induced forward transfer.
AB  - We report the Laser Induced Forward Transfer (LIFT) of antibodies from a liquid
      donor film onto paper receivers for application as point-of-care diagnostic
      sensors. To minimise the loss of functionality of the active biomolecules during
      transfer, a dynamic release layer was employed to shield the biomaterial from
      direct exposure to the pulsed laser source. Cellulose paper was chosen as the
      ideal receiver because of its inherent bio-compatibility, liquid transport
      properties, wide availability and low cost, all of which make it an efficient and
      suitable platform for point-of-care diagnostic sensors. Both enzyme-tagged and
      untagged IgG antibodies were LIFT-printed and their functionality was confirmed
      via a colorimetric enzyme-linked immunosorbent assay. Localisation of the printed
      antibodies was exhibited, which can allow the creation of complex 2-d patterns
      such as QR codes or letters for use in a final working device. Finally, a
      calibration curve was determined that related the intensity of the colour
      obtained to the concentration of active antibodies to enable quantitative
      assessment of the device performance. The motivation for this work was to
      implement a laser-based procedure for manufacturing low-cost, point-of-care
      diagnostic devices on paper. 

PMID- 24926393
TI  - Flow-through electroporation of mammalian cells in decoupled flow streams using
      microcapillaries.
AB  - We report on reversible electroporation of cells in a flow-through microfluidic
      device, whereby the required electric field is delivered through a set of
      integrated microcapillaries between a centre stream of cells and side streams of
      liquid electrolytes. The electrolytes are applied with a sine wave voltage and
      cells flow by the microcapillary openings encounter a burst of ac field with a
      duration and strength determined by their average speed and spatial proximity to
      the microcapillary openings, respectively. Effectiveness of the approach is
      presented through numerical simulations and empirical results on electroporation
      efficiency and cell viability against various flow rates (exposure time to the
      field) as well as frequencies and root-mean-square (rms) intensities of the
      field. High frequencies (80-400 kHz) and high intensities (e.g., 1.6 kV/cm, rms)
      are identified with increased electroporation efficiency 61% and viability 86% on
      average. These results suggest that the device demonstrated here with a simple
      design and robust operation offers a viable platform for flow-through
      electroporation. 

PMID- 24926395
TI  - Establishing community advisory boards for clinical trial research in Malawi:
      engendering ethical conduct in research.
AB  - In this article I deal with extending the ethical principles of research to
      include communities through the establishment of Community Advisory Boards
      (CABs). The aim of the project on which this article is based demonstrates the
      need for protecting communities that participate in research in order to
      stimulate ethical conduct in research in Malawi. In the article, I provide an
      overview on the role and functions of CABs. I discuss the establishment of CABs
      in Malawi and present descriptions of the processes and challenges involved. I
      conclude by sharing experiences of some of the key lessons learnt from the
      establishment of CABs. 

PMID- 24926394
TI  - Barriers and disparities in emergency medical services 911 calls for stroke
      symptoms in the United States adult population: 2009 BRFSS Survey.
AB  - INTRODUCTION: This study examines barriers and disparities in the intentions of
      American citizens, when dealing with stroke symptoms, to call 911. This study
      hypothesizes that low socioeconomic populations are less likely to call 911 in
      response to stroke recognition. METHODS: The study is a cross-sectional design
      analyzing data from the Centers for Disease Control's 2009 Behavioral Risk Factor
      Surveillance Survey, collected through a telephone-based survey from 18 states
      and the District of Columbia. The study identified the 5 most evident stroke
      warning symptoms based on those given by the American Stroke Association. We
      conducted appropriate weighting procedures to account for the complex survey
      design. RESULTS: A total of 131,988 respondents answered the following question:
      "If you thought someone was having a heart attack or a stroke, what is the first
      thing you would do?" A majority of those who said they would call 911 were
      insured (85.1%), had good health (84.1%), had no stroke history (97.3%), had a
      primary care physician (PCP) (81.4%), and had no burden of medical costs (84.9%).
      Those less likely to call 911 were found in the following groups: 65 years or
      older, men, other race, unmarried, less than or equal to high school degree, less
      than $25,000 family income, uninsured, no PCP, burden of medical costs, fair/poor
      health, previous history of strokes, or interaction between burden of medical
      costs and less than $50,000 family income (p<0.0001 by X(2) tests). The only
      factors significantly associated with "would call 911" were age, sex,
      race/ethnicity, marital status, and previous history of strokes. CONCLUSION:
      Barriers and disparities exist among subpopulations of different socioeconomic
      statuses. This study suggests that some potential stroke victims could have
      limited access to EMS services. Greater effort targeting certain populations is
      needed to motivate citizens to call 911.

PMID- 24926396
TI  - Safety assessment in primary Mycobacterium tuberculosis smear microscopy centres
      in Blantyre Malawi: a facility based cross sectional survey.
AB  - INTRODUCTION: Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is
      transmitted mainly through aerosolization of infected sputum which puts
      laboratory workers at risk in spite of the laboratory workers' risk of infection
      being at 3 to 9 times higher than the general public. Laboratory safety should
      therefore be prioritized and optimized to provide sufficient safety to laboratory
      workers. OBJECTIVE: To assess the safety for the laboratory workers in TB primary
      microscopy centres in Blantyre urban. METHODOLOGY: TB primary microscopy centers
      in Blantyre urban were assessed in aspects of equipment availability, facility
      layout, and work practice, using a standardized WHO/AFRO ISO 15189 checklist for
      the developing countries which sets the minimum safety score at >=80%. Each
      center was graded according to the score it earned upon assessment. RESULTS: Only
      one (1) microscopy center out nine (9) reached the minimum safety requirement.
      Four (4) centers were awarded 1 star level, four (4) centers were awarded 2 star
      level and only one (1) center was awarded 3 star level. CONCLUSION: In Blantyre
      urban, 89% of the Tuberculosis microscopy centers are failing to provide the
      minimum safety to the laboratory workers. Government and other stake holders
      should be committed in addressing the safety challenges of TB microscopy centres
      in the country to ensure safety for the laboratory workers. RECOMMENDATIONS: It
      is recommended that the study be conducted at the regional or national level for
      both public and private laboratories in order to have a general picture of safety
      in Tb microscopy centres possibly across the country.

PMID- 24926397
TI  - Knowledge and perceptions of quality of obstetric and newborn care of local
      health providers: a cross-sectional study in three districts in Malawi.
AB  - AIM: Quality of service delivery for maternal and newborn health in Malawi is
      influenced by human resource shortages and knowledge and care practices of the
      existing service providers. We assessed Malawian healthcare providers' knowledge
      of management of routine labour, emergency obstetric care and emergency newborn
      care; correlated knowledge with reported confidence and previous study or
      training; and measured perception of the care they provided. METHODS: This study
      formed part of a large-scale quality of care assessment in three districts
      (Kasungu, Lilongwe and Salima) of Malawi. Subjects were selected purposively by
      their role as providers of obstetric and newborn care during routine visits to
      health facilities by a research assistant. Research assistants introduced and
      supervised the self-completed questionnaire by the service providers. Respondents
      included 42 nurse midwives, 1 clinical officer, 4 medical assistants and 5 other
      staff. Of these, 37 were staff working in facilities providing Basic Emergency
      Obstetric Care (BEMoC) and 15 were from staff working in facilities providing
      Comprehensive Emergency Obstetric Care (CEMoC). RESULTS: Knowledge regarding
      management of routine labour was good (80% correct responses), but knowledge of
      correct monitoring during routine labour (35% correct) was not in keeping with
      internationally recognized good practice. Questions regarding emergency obstetric
      care were answered correctly by 70% of respondents with significant variation
      depending on clinicians' place of work. Knowledge of emergency newborn care was
      poor across all groups surveyed with 58% correct responses and high rates of
      potentially life-threatening responses from BEmOC facilities. Reported confidence
      and training had little impact on levels of knowledge. Staff in general reported
      perception of poor quality of care. CONCLUSION: Serious deficiencies in
      providers' knowledge regarding monitoring during routine labour and management of
      emergency newborn care were documented. These may contribute to maternal and
      neonatal deaths in Malawi. The knowledge gap cannot be overcome by simply
      providing more training.

PMID- 24926398
TI  - Therapeutic commitment for general nurses in dealing with mental health problems
      of people living with HIV/AIDS in Blantyre, Malawi.
AB  - INTRODUCTION: Therapeutic commitment of general nurses influences their provision
      of mental health care to clients. It is the general nurses' predisposition for
      working therapeutically with clients who have mental health problems (MHPs). In
      Malawi, general nurses are the majority of health care professionals who care for
      people living with HIV/AIDS (PLWHA) and they are expected to deal with the mental
      health problems of these patients. The provision of mental health care to PLWHA
      is vital because apart from the physical illnesses associated with the virus,
      these people are also affected by mental health problems. However, most general
      nurses, feel neither confident nor competent when dealing with the mental health
      problems of their clients in Malawi. This may negatively influence their
      therapeutic commitment in dealing with mental health problems of PLWHA. However,
      therapeutic commitment of general nurses in providing mental health care to PLWHA
      in Malawi remains unknown. MATERIALS AND METHODS: The study used a quantitative
      descriptive survey design. a convenient sample comprising of 136 general nurses
      was used and data was collected using Mental Health Problems Perception
      Questionnaire. Permission to use the tool in this study was granted by Prof.
      Lauder. Ethical approval to conduct the study was granted by Ethics Committees at
      University of KwaZulu Natal and University of Malawi. Data were analysed using
      Statistical Package for Social Sciences version 15.0. RESULTS: The study findings
      revealed that there is a linear relationship between general nurses' levels of
      knowledge and skills and their therapeutic commitment (r=.40, n=136, p<.05) to
      provide mental health care of PLWHA. CONCLUSION: This study suggests general
      nurses' levels of therapeutic commitment in dealing with MHPs of PLWHA vary and
      their levels of knowledge and skill to deal with MHPs influence their willingness
      to provide mental health care to PLWHA.

PMID- 24926399
TI  - Interpreting and dismissing the relevance of the "wait and wipe" finding from the
      circumcision studies conducted in Africa.
AB  - Some of the secondary findings from the circumcision studies conducted in Africa,
      are both interesting and difficult to explain. This paper focuses on the finding
      that uncircumcised men who waited for ten minutes after sexual intercourse and
      then wiped their penises using a dry cloth, had lower rates of HIV infection
      compared to those who cleaned using a wet cloth or those who cleaned within three
      minutes of having intercourse. The paper also focuses on the finding on men who
      became infected and yet they reported no sexual acts or 100% condom use.
      Interpretations that have been provided so far in trying to explain these two
      interesting findings are somewhat inadequate. Because of the inadequate
      interpretation that has been provided, anti-circumcision lobbyist are presenting
      the "wait and wipe strategy" as an alternative to circumcision for HIV
      prevention. In this paper, we argue that waiting for ten minutes and wiping with
      a dry cloth does not prevent men from becoming infected by HIV. We therefore
      attempt to present some alternative views. 

PMID- 24926400
TI  - Management of diabetic retinopathy.
AB  - Sub-Saharan Africa faces an epidemic of diabetes. Visual loss from diabetic
      retinopathy (DR) is both preventable and treatable. This article reviews the
      epidemiology and clinical features of DR and current evidence-based interventions
      in three areas: primary prevention of retinopathy by optimum medical management,
      early detection of pre-symptomatic disease and management of established
      retinopathy to prevent or mitigate visual loss. There are significant challenges
      to DR care in resource poor environments. Appropriate provision of effective
      interventions by health services can reduce social and economic costs associated
      with patient care. 

PMID- 24926401
TI  - A 6 year-old boy was referred from a district hospital with congestive cardiac
      failure.

PMID- 24926402
TI  - "I have always wondered why there is relatively such a large burden of infectious
      diseases in our part of Africa and the world..." Dr Chisomo Msefula talks to
      Thengo Kavinya on his career.

PMID- 24926403
TI  - Cell Therapy Strategies vs. Paracrine Effect in Huntington's Disease.
AB  - Huntington's disease (HD) is a genetic neurodegenerative disorder. The most
      common symptom of HD is abnormal involuntary writhing movements, called chorea.
      Antipsychotics and tetrabenazine are used to alleviate the signs and symptoms of
      HD. Stem cells have been investigated for use in neurodegenerative disorders to
      develop cell therapy strategies. Recent evidence indicates that the beneficial
      effects of stem cell therapies are actually mediated by secretory molecules, as
      well as cell replacement. Although stem cell studies show that cell
      transplantation provides cellular improvement around lesions in in vivo models,
      further work is required to elucidate some issues before the clinical application
      of stem cells. These issues include the precise mechanism of action, delivery
      method, toxicity and safety. With a focus on HD, this review summarizes cell
      therapy strategies and the paracrine effect of stem cells. 

PMID- 24926404
TI  - The frequency and severity of gastrointestinal symptoms in patients with early
      Parkinson's disease.
AB  - OBJECTIVE: Although gastrointestinal dysfunctions occur in the majority of
      patients with Parkinson's disease (PD), they are often unrecognized because many
      patients remain relatively asymptomatic in the early stage. We investigated the
      frequency of gastrointestinal symptoms in patients with PD using newly developed
      gastrointestinal symptom questionnaires. METHODS: Early PD patients with a
      symptom duration not exceeding 3 years were included in this study. All PD
      patients were evaluated using a questionnaire, which consisted of three relevant
      domains: oropharyngoesophageal (10 items); gastric (3 items); and intestinal
      anorectal (7 items). The frequency of symptoms was calculated as a proportion
      with an item score >= 2. RESULTS: Of the 54 patients enrolled, 48 patients
      (88.9%) responded that bowel symptoms developed before the onset of Parkinsonian
      motor symptoms, and four patients reported that the onset of two types of
      symptoms (i.e., bowel and neurological) occurred approximately simultaneously,
      with only months between them. The frequencies of gastrointestinal symptoms are
      as follows: speech disturbance (40.7%), drooling (24.1%), sense of getting stuck
      (31.5%), choking (27.8%), globus pharyngis (16.7%), repetitive deglutition
      (29.6%), pain during swallowing (5.6%), food regurgitation (3.7%), acid reflux
      (7.4%), nausea/vomiting (11.1%), early satiety (16.7%), postprandial fullness
      (14.8%), epigastric soreness (9.3%), abdominal pain (3.7%), constipation (46.3%),
      excessive strain during defecation (33.3%), fecal incontinence (7.4%), tenesmus
      (20.4%), loose stool or diarrhea (3.7%), and difficulty in relaxing anal
      sphincter (11.1%). Two patients were scored at zero. CONCLUSIONS: Our findings
      confirm that gastrointestinal dysfunction occurs in early PD in relatively high
      frequency.

PMID- 24926405
TI  - Correlation of sleep disturbance and cognitive impairment in patients with
      Parkinson's disease.
AB  - OBJECTIVE: Cognitive impairment is a common nonmotor symptom of Parkinson's
      disease (PD) and is associated with high mortality, caregiver distress, and
      nursing home placement. The risk factors for cognitive decline in PD patients
      include advanced age, longer disease duration, rapid eye movement sleep behavior
      disorder, hallucinations, excessive daytime sleepiness, and nontremor symptoms
      including bradykinesia, rigidity, postural instability, and gait disturbance. We
      conducted a cross-sectional study to determine which types of sleep disturbances
      are related to cognitive function in PD patients. METHODS: A total of 71 PD
      patients (29 males, mean age 66.46 +/- 8.87 years) were recruited. All patients
      underwent the Mini- Mental State Examination (MMSE) and the Korean Version of the
      Montreal Cognitive Assessments (MoCA-K) to assess global cognitive function.
      Sleep disorders were evaluated with the Stanford Sleepiness Scale, Epworth
      Sleepiness Scale, Insomnia Severity Index (ISI), Pittsburg Sleep Quality Index,
      and Parkinson's Disease Sleep Scale in Korea (PDSS). RESULTS: The ISI was
      correlated with the MMSE, and total PDSS scores were correlated with the MMSE and
      the MoCA-K. In each item of the PDSS, nocturnal restlessness, vivid dreams,
      hallucinations, and nocturnal motor symptoms were positively correlated with the
      MMSE, and nocturnal restlessness and vivid dreams were significantly related to
      the MoCA-K. Vivid dreams and nocturnal restlessness are considered the most
      powerful correlation factors with global cognitive function, because they
      commonly had significant correlation to cognition assessed with both the MMSE and
      the MoCA-K. CONCLUSIONS: We found a correlation between global cognitive function
      and sleep disturbances, including vivid dreams and nocturnal restlessness, in PD
      patients.

PMID- 24926406
TI  - Stiff-person syndrome: case series.
AB  - Stiff-person syndrome (SPS) is a rare disorder, characterized by progressive
      fluctuating muscular rigidity and spasms. Glutamic acid decarboxylase (GAD)
      antibody is primarily involved in the pathogenesis of SPS and SPS is strongly
      associated with other autoimmune disease. Here we report three cases of patients
      with classical SPS finally confirmed by high serum level of GAD antibodies. All
      of our patients respond favorably to gamma amino butyric acid-enhancing drugs and
      immunotherapies. 

PMID- 24926407
TI  - Giant middle fossa epidermoid presenting as holmes' tremor syndrome.
AB  - Intracranial dermoids may gradually reach an enormous size before the onset of
      symptoms. Common clinical presentations of intracranial epidermoid include
      headache and seizures. We present a case of a 35-year female patient with giant
      middle fossa epidermoid that presented with Holmes' tremor syndrome, and we
      review the relevant literature. To the best of our knowledge, such a presentation
      has not previously been described in the literature. 

PMID- 24926408
TI  - Rhabdomyolysis related to dyskinesia in Parkinson's disease.
AB  - Rhabdomyolysis is a life threatening syndrome. It accounts for an estimated 8% to
      15% of cases of acute renal failure and is associated with a mortality rate of
      5%. In movement disorders, various causes of rhabdomyolysis have been reported
      including status dystonicus, myoclonus, generalized chorea and parkinsonism
      hyperprexia syndrome in Parkinson's disease (PD). Levodopa-induced dyskinesia
      leading to rhabdomyolysis is a very rare phenomenon in PD. We report a case of 76
      years old PD patient with dyskinesia and rhabdomyolysis. 

PMID- 24926409
TI  - Suppression of myoclonus in corticobasal degeneration by levetiracetam.
AB  - Myoclonus in corticobasal degeneration (CBD) has often been associated with
      severe and difficult to treat disabilities. Levetiracetam is a new antiepileptic
      agent with antimyoclonic effects. Herein, we present a 72-year-old woman with
      clinically probable CBD and with spontaneous rhythmic myoclonus in the right
      foot, which was markedly ameliorated through treatment with levetiracetam. The
      effect of levetiracetam was associated with the decreased amplitude of enlarged
      cortical somatosensory evoked potentials. This result suggests that the
      antimyoclonic effect of levetiracetam might be mediated through the suppression
      of increased cortical excitability. 

PMID- 24926410
TI  - Chemoselective enrichment for natural products discovery.
AB  - Natural products account for a significant proportion of modern day therapeutic
      agents. However, the discovery of novel compounds is hindered by the isolation
      process, which often relies upon extraction and chromatographic separation
      techniques. These methods, which are dependent upon the physicochemical
      properties of the compounds, have a limited ability to both purify and
      concentrate the minor components of a biological extract. We have devised an
      isolation strategy based upon an orthogonal chemical feature, namely, functional
      group composition. Development of a functional group-targeted method is expected
      to achieve exceptional resolution given the large number of distinct moieties
      present in natural product extracts. Here, we describe the generation of
      controllably reversible covalent enrichment tags for the chemoselective isolation
      of alcohol-containing natural products from complex mixtures.

PMID- 24926411
TI  - Resumption of menses in anorexia nervosa during a course of family-based
      treatment.
AB  - BACKGROUND: The resumption of menses (ROM) is considered an important clinical
      marker in weight restoration for patients with anorexia nervosa (AN). The purpose
      of this study was to examine ROM in relation to expected body weight (EBW) and
      psychosocial markers in adolescents with AN. METHODS: We conducted a
      retrospective chart review at The University of Chicago Eating Disorders Program
      from September 2001 to September 2011 (N = 225 females with AN). Eighty-four
      adolescents (Mean age = 15.1, SD = 2.2) with a DSM-IV diagnosis of AN, presenting
      with secondary amenorrhea were identified. All participants had received a course
      of outpatient family-based treatment (FBT), i.e., ~20 sessions over 12 months.
      Weight and menstrual status were tracked at each therapy session throughout
      treatment. The primary outcome measures were weight (percent of expected for sex,
      age and height), and ROM. RESULTS: Mean percent EBW at baseline was 82.0 (SD =
      6.5). ROM was reported by 67.9% of participants (57/84), on average at 94.9 (SD =
      9.3) percent EBW, and after having completed an average of 13.5 (SD = 10.7) FBT
      sessions (~70% of standard FBT). Compared to participants without ROM by
      treatment completion, those with ROM had significantly higher baseline Eating
      Disorder Examination Global scores (p = .004) as well as Shape Concern (p < .008)
      and Restraint (p < .002) subscale scores. No other differences were found.
      CONCLUSIONS: Results suggest that ROM occur at weights close to the reference
      norms for percent EBW, and that high pre-treatment eating disorder
      psychopathology is associated with ROM. Future research will be important to
      better understand these differences and their implications for the treatment of
      adolescents with AN.

PMID- 24926413
TI  - Design and implementation of a randomized controlled trial of genomic counseling
      for patients with chronic disease.
AB  - We describe the development and implementation of a randomized controlled trial
      to investigate the impact of genomic counseling on a cohort of patients with
      heart failure (HF) or hypertension (HTN), managed at a large academic medical
      center, the Ohio State University Wexner Medical Center (OSUWMC). Our study is
      built upon the existing Coriell Personalized Medicine Collaborative (CPMC(r)).
      OSUWMC patient participants with chronic disease (CD) receive eight actionable
      complex disease and one pharmacogenomic test report through the CPMC(r) web
      portal. Participants are randomized to either the in-person post-test genomic
      counseling-active arm, versus web-based only return of results-control arm. Study
      specific surveys measure: (1) change in risk perception; (2) knowledge retention;
      (3) perceived personal control; (4) health behavior change; and, for the active
      arm (5), overall satisfaction with genomic counseling. This ongoing partnership
      has spurred creation of both infrastructure and procedures necessary for the
      implementation of genomics and genomic counseling in clinical care and clinical
      research. This included creation of a comprehensive informed consent document and
      processes for prospective return of actionable results for multiple complex
      diseases and pharmacogenomics (PGx) through a web portal, and integration of
      genomic data files and clinical decision support into an EPIC-based electronic
      medical record. We present this partnership, the infrastructure, genomic
      counseling approach, and the challenges that arose in the design and conduct of
      this ongoing trial to inform subsequent collaborative efforts and best genomic
      counseling practices. 

PMID- 24926414
TI  - Medicare-Medicaid eligible beneficiaries and potentially avoidable
      hospitalizations.
AB  - OBJECTIVE: Potentially avoidable hospitalizations have been identified by experts
      as leading to poor health outcomes and costly care. Potentially avoidable
      hospitalizations are particularly common among full-benefit dual eligible
      beneficiaries. This paper examines potentially avoidable hospitalizations rates
      by setting, state, and medical condition, and the average cost of these events.
      METHODS: This analysis identifies potentially avoidable hospitalizations using
      diagnosis codes identified by an expert panel. Settings of care are determined
      using a timeline file, which assigns an individual to a specific setting on a
      particular day. POPULATION/DATA SOURCE: The analysis uses several different
      datasets from the Chronic Conditions Data Warehouse. The study population
      includes fee-for-service beneficiaries who were eligible for both Medicare and
      full Medicaid benefits for at least one month during the calendar year. The study
      years are 2007 to 2009. RESULTS: In 2009, among our study population, 26 percent
      of hospitalizations were potentially avoidable; and the rate was 133 per 1,000
      person-years. Potentially avoidable hospitalizations were much more likely for
      those beneficiaries who were in institutions--16 percent of beneficiaries in our
      study population were in an institution, yet comprised 45 percent of all
      potentially avoidable hospitalizations. The range in rates across the states was
      considerable, with more than a threefold difference across states. Five
      conditions were responsible for nearly 80 percent of potentially avoidable
      hospitalizations. From 2007 to 2009, the national and state rates were fairly
      consistent. DISCUSSION: This analysis indicates that the potentially avoidable
      hospitalization rate among MME beneficiaries was consistently high from 2007 to
      2009. This bears monitoring in the future to see if the Centers for Medicare &
      Medicaid Services' various initiatives have led to a reduction in rates.

PMID- 24926412
TI  - The child and adolescent athlete: a review of three potentially serious injuries.
AB  - The increased participation of children and adolescents in organized sports
      worldwide is a welcome trend given evidence of lower physical fitness and
      increased prevalence of overweight in this population. However, the increased
      sports activity of children from an early age and continued through the years of
      growth, against a background of their unique vulnerability to injury, gives rise
      to concern about the risk and severity of injury. Three types of injury-anterior
      cruciate ligament (ACL) injury, concussion, and physeal injury - are considered
      potentially serious given their frequency, potential for adverse long-term health
      outcomes, and escalating healthcare costs. Concussion is probably the hottest
      topic in sports injury currently with voracious media coverage and exploding
      research interest. Given the negative cognitive effects of concussion, it has the
      potential to have a great impact on children and adolescents during their
      formative years and potentially impair school achievement and, if concussion
      management is not managed appropriately, there can be long term negative impact
      on cognitive development and ability to resume sports participation. Sudden and
      gradual onset physeal injury is a unique injury to the pediatric population which
      can adversely affect growth if not managed correctly. Although data are lacking,
      the frequency of stress-related physeal injury appears to be increasing. If
      mismanaged, physeal injuries can also lead to long-term complications which could
      negatively affect ability to participate in sports. Management of ACL injuries is
      an area of controversy and if not managed appropriately, can affect long-term
      growth and recovery as well as the ability to participate in sports. This article
      considers the young athlete's vulnerability to injury, with special reference to
      ACL injury, concussion, and physeal injury, and reviews current research on
      epidemiology, diagnosis, treatment, and prevention of these injury types. This
      article is intended as an overview of these injury types for medical students,
      healthcare professionals and researchers. 

PMID- 24926415
TI  - Medicare post-acute care episodes and payment bundling.
AB  - BACKGROUND: The purpose of this paper is to examine service use in an episode of
      acute and post-acute care (PAC) under alternative episode definitions and to look
      at geographic differences in episode payments. DATA AND METHODS: The data source
      for these analyses was a Medicare claims file for 30 percent of beneficiaries
      with an acute hospital initiated episode in 2008 (N = 1,705,794, of which 38.7
      percent went on to use PAC). Fixed length episodes of 30, 60, and 90 days were
      examined. Analyses examined differences in definitions allowing any claim within
      the fixed length period to be part of the episode versus prorating a claim
      extending past the episode endpoint. Readmissions were also examined as an
      episode endpoint. Payments were standardized to allow for comparison of episode
      payments per acute hospital discharge or PAC user across states. RESULTS: The
      results of these analyses provide information on the composition of service use
      under different episode definitions and highlight considerations for providers
      and payers testing different alternatives for bundled payment.

PMID- 24926417
TI  - Salvage therapy with high dose Intravenous Immunoglobulins in acquired Von
      Willebrand Syndrome and unresponsive severe intestinal bleeding.
AB  - A 91-year-old woman affected with acquired Von Willebrand (VW) syndrome and
      intestinal angiodysplasias presented with severe gastrointestinal bleeding
      (hemoglobin 5 g/dl). Despite replacement therapy with VW factor/factor VIII
      concentrate qid, bleeding did not stop (eleven packed red blood cell units were
      transfused over three days). High circulating levels of anti-VW factor
      immunoglobulin M were documented immunoenzimatically. Heart ultrasound showed
      abnormalities of the mitral and aortic valves with severe flow alterations. When
      intravenous immunoglobulins were added to therapy, prompt clinical and laboratory
      responses occurred: complete cessation of bleeding, raise in hemoglobin, VW
      factor antigen, VW ristocetin cofactor and factor VIII levels as well as
      progressive reduction of the anti-VWF autoantibody levels. 

PMID- 24926416
TI  - The impact of Medicaid peer support utilization on cost.
AB  - BACKGROUND: Peer support programs have proliferated over the past decade,
      building on recovery oriented programming, yet relationships between peer support
      services and the costs to public programs have not been well described in
      literature. The purpose of this study is to fill gaps in the literature related
      to peer support programs and cost: lack of comparison groups, small sample sizes,
      and the availability of research examining utilization of Medicaid mental health
      services. METHODS: The study employed a retrospective design with treatment and
      comparison groups created from three administrative databases. Three ordinary
      least squares regression models were constructed to predict crisis stabilization
      cost, psychiatric hospitalization cost, and total Medicaid cost while controlling
      for other factors. The Chronic Illness and Disability Payment System + Rx was
      used to control for illness severity. RESULTS: Peer support was associated with
      $5,991 higher total Medicaid cost (p < .01). Peer support was also associated
      with higher crisis stabilization cost and lower psychiatric hospitalization cost,
      but the relationships were not statistically significant. Peer support was
      associated with $2,100 higher prescription drug cost (p < .01), $5,116 higher
      professional services cost (p < .01), and $1,225 lower facility cost (p < .01).
      CONCLUSIONS: While the implementation of Medicaid financed peer support programs
      may not result in savings from reductions of costly crisis stabilizations and
      psychiatric hospitalizations, it does support the principles of self-direction
      and recovery from severe mental illness. State policy makers must weigh the
      potential higher cost associated with peer support programs with efforts to
      redesign the delivery of mental health services.

PMID- 24926418
TI  - Reduced Specificity in Episodic Future Thinking in Posttraumatic Stress Disorder.
AB  - Posttraumatic stress disorder (PTSD), one of the most common disorders following
      trauma, has been associated with a tendency to remember past personal memories in
      a nonspecific, overgeneral way. The present study investigated whether such a
      bias also applies to projections of future personal events. Trauma survivors (N =
      50) generated brief descriptions of imagined future experiences in response to
      positive and negative cues in a future-based Autobiographical Memory Test.
      Survivors with PTSD imagined fewer specific future events in response to
      positive, but not to negative, cues, compared to those without PTSD. This effect
      was independent of comorbid major depression. Reduced memory specificity in
      response to positive cues was related to appraisals of foreshortened future and
      permanent change. Training to enhance specificity of future projections may be
      helpful in PTSD and protect against potentially toxic effects of autobiographical
      memory overgenerality.

PMID- 24926419
TI  - Geochemical modeling and multivariate statistical evaluation of trace elements in
      arsenic contaminated groundwater systems of Viterbo Area, (Central Italy).
AB  - Contamination of groundwater by naturally occurring arsenic has recently become a
      disturbing environmental problem in Viterbo area, Central Italy. Arsenic
      concentrations in most of the public supply networks exceed the maximum allowable
      limit of 10 MUg/l (WHO) for drinking water. The primary purpose of this paper is
      to obtain a better understanding of the factors contributing to the high levels
      of As in water supply networks. This study focuses on (a) the determination of
      basic hydrochemical characteristics of groundwater, (b) the identification of the
      major sources and processes controlling the As contamination in public supply
      networks, (c) to find out possible relationships among the As and other trace
      elements through principal component analysis (PCA). Groundwater samples from
      public water supply wells and springs were collected and analysed for physico
      chemical parameters and trace elements. Springs and well water samples are
      predominantly of the Na-HCO3, Na -Ca-HCO3 and Ca-HCO3 types and the highest
      arsenic concentrations were observed in Na-HCO3 type water. Eh-pH diagrams reveal
      that H2AsO4 (-) and HAsO4 (2-), As(V) arsenate, are the dominating As species
      highlighting slightly to moderately oxidizing conditions. Geochemical modeling
      indicates that arsenic-bearing phases were undersaturated in the groundwater,
      however most of the samples were saturated with respect to Fe (i.e. magnetite,
      hematite and goethite) and Al (diaspore and boehmite) oxide and hydroxide
      minerals. Concentrations of As, Li, B, Co, Sr, Mo, U and Se are highly correlated
      (r > 0.7) with each other, however in some groundwater samples As show also good
      correlations (r > 0.5) with Fe and Mn elements reflecting the relationships among
      the trace elements result from different geochemical processes. Evaluation of the
      principal component (PCA) analysis and geochemical modeling suggest that the
      occurrence of As and other trace element concentrations in groundwater are
      probably derived from (i) weathering and/or dissolution of volcanic source
      aquifer materials and (ii) adsorption/desorption processes on the Fe and Al oxide
      and hydroxide minerals. 

PMID- 24926420
TI  - Characteristics and chemical compositions of propolis from Ethiopia.
AB  - INTRODUCTION: Propolis is a sticky material mixed by honeybees to utilize it in
      protecting their hives from infection by bacteria and fungi. The therapeutic
      properties of propolis are due to its chemical composition with bio-active
      compounds; therefore, researchers are interested in studying its chemical
      constituents and biological properties. The main objective of this study is to
      determine the chemical compositions, characteristics and relative concentrations
      of organic compounds in the extractable organic matter of propolis samples
      collected from four different areas in Ethiopia. RESULTS: The propolis samples
      were extracted with a mixture of dichloromethane and methanol and analyzed by gas
      chromatography-mass spectrometry (GC-MS).The results showed that the total
      extract yields ranged from 27.2% to 64.2% (46.7 +/- 19.1%). The major compounds
      were triterpenoids (85.5 +/- 15.0% of the total extracts, mainly alpha-, beta
      amyrins and amyryl acetates), n-alkanes (5.8 +/- 7.5%), n-alkenes (6.2 +/-
      7.0%,), methyl n-alkanoates (0.4 +/- 0.2%), and long chain wax esters (0.3 to
      2.1%). CONCLUSION: The chemical compositions of these propolis samples indicate
      that they are potential sources of natural bio-active compounds for biological
      and pharmacological applications.

PMID- 24926421
TI  - fAFLP analysis of Brazilian Bacillus thuringiensis isolates.
AB  - A total of 65 Bacillus thuringiensis (Bt) isolates were subjected to analysis of
      genetic relationship using fAFLP (fluorescent Fragment Length Polymorphism), in
      order to determine the genetic diversity within a group of Bt strains. 26 strains
      from different subspecies were identified as it follows: 9 kindly provided by the
      USDA (United States Department of Agriculture), 9 kindly provided by the
      Institute Pasteur and eight from Embrapa Maize and Sorghum Bt Collection, and 39
      strains with no subspecies information also from Embrapa's Bt Collection. DNA
      sample was double digested with restriction enzymes EcoRI and MseI, and the
      fragments were linked to adapters. Selective amplification reactions were
      performed using five primer combinations and the amplified fragments were
      separated by gel electrophoresis on an ABI377 sequencer. Genetic distances were
      obtained by the complement of the Jaccard coefficient and the groups were
      performed by the UPGMA method. Five primer combinations generated 495 scorable
      fragments and 483 were found to be polymorphic. Out of 26 subspecies, strains 344
      and T09 (B. thuringiensis subsp. tolworthi) showed the highest similarity (15%),
      while isolates HD3 B. thuringiensis subsp finitimus and T24 B. thuringiensis
      subsp neoleonensis were the most genetically distant (92%). B. thuringiensis
      isolates with no subspecies identification, found in samples from Goias State
      showed higher similarity forming a group with an average distance of 6%, and the
      closest subspecies to this group was B. thuringiensis subsp thuringiensis (HD2)
      with 52% of similarity. This similarity may be due to the fact that these
      organism exchange genetic material by conjugation, and it is relatively common to
      have evolutionary characteristics of their ancestors. 

PMID- 24926422
TI  - Identification and cost of adverse events in metastatic breast cancer in taxane
      and capecitabine based regimens.
AB  - PURPOSE: We sought to compare the economic impact of treatment-related adverse
      events (AEs) in patients with metastatic breast cancer (mBC) using taxane- or
      capecitabine-based treatment regimens as either first- or second-line (FL or SL)
      therapy in the US. METHODS: We used healthcare claims data from the Truven Health
      Analytics MarketScan(r) Commercial Databases to conduct a retrospective cohort
      study comparing the economic impact of AEs amongst taxane- and capecitabine
      treated mBC patients in the US. We selected women diagnosed with mBC between 2008
      2010 who received a taxane or capecitabine as first- or second-line (FL or SL)
      chemotherapy. Costs related to hospitalization, outpatient services, emergency
      department visits, chemotherapy and other medications were tabulated and combined
      to determine total healthcare costs. The incremental monthly costs associated
      with the presence of AEs compared to no AEs were estimated using generalized
      linear models, controlling for age and Charlson Comorbidity Index. RESULTS: We
      identified 15,443 mBC patients meeting inclusion criteria. Adjusted total monthly
      costs were significantly higher in those who experienced AEs than in those
      without AEs in both lines of treatment (FL incremental cost: taxanes $1,142,
      capecitabine $1,817; SL incremental cost: taxanes $1,448, capecitabine $4,437).
      Total costs increased with the number of AEs and were primarily driven by
      increased hospitalization amongst those with AEs. CONCLUSIONS: Adverse events in
      taxane- or capecitabine-treated mBC patients are associated with significant
      increases in costs. Selecting treatment options associated with fewer AEs may
      reduce costs and improve outcomes in these patients.

PMID- 24926423
TI  - Colloid stability of iron compounds in groundwater of Western Siberia.
AB  - The paper reports on experimental modeling of the colloid system composition in
      natural groundwater. Iron hydroxide is found to be the main component of natural
      colloid systems. It is shown that silicon compounds and dissolved organic
      substances (DOS) stabilize iron hydroxide (III), forming a stable colloid system,
      and preclude coagulation. The presented results suggest that CaCl2 and AlCl3
      electrolytes affect the coagulation stability of synthesized model colloid
      solutions. 

PMID- 24926424
TI  - 33 Ironman triathlons in 33 days-a case study.
AB  - This case report presents the performance of an athlete who completed for the
      first time in history the total distance of 33 Ironman triathlons within 33
      consecutive days. The athlete finished the total distance of 7,458 km (i.e. 125
      km swimming, 5,940 km cycling and 1,393 km running) within a total time of 410 h
      and a mean time of 12 h 27 min per Ironman distance. During the 33 days, the
      athlete became slower in swimming (r(2) = 0.27, p = 0.0019), transition time 1
      (r(2) = 0.66, p < 0.001), and transition time 2 (r(2) = 0.48, p < 0.0001).
      However, in cycling (r(2) = 0.07, p = 0.13), running (r(2) = 0.04, p = 0.25) and
      overall race time (r(2) = 0.10, p = 0.069), the athlete was able to maintain his
      performance during the 33 days. The coefficients of variation (CV) for the split
      times in swimming, cycling, running and overall race times were very low (i.e.
      2.7%, 3.2%, 4.7%, and 2.7%, respectively) whereas the CV for transition times 1
      and 2 were considerably higher (i.e. 25.5% and 55.5%, respectively). During the
      33 days, body mass decreased from 83.0 kg to 80.5 kg (r(2) = 0.55, p < 0.0001).
      Plasma [Na(+)] remained within the reference range, creatine kinase, blood
      glucose and liver enzymes were minimally elevated above the reference range after
      four of five stages where blood analyses were performed. This case report shows
      that this athlete finished 33 Ironman triathlons within 33 consecutive days with
      minor variations over time (i.e. even pacing) in both split times and overall
      race times. This performance was most probably due to the high experience of the
      athlete, his pacing strategy and the stable environmental conditions. 

PMID- 24926425
TI  - Elevated copper in the amyloid plaques and iron in the cortex are observed in
      mouse models of Alzheimer's disease that exhibit neurodegeneration.
AB  - BACKGROUND: In Alzheimer's disease (AD), alterations in metal homeostasis,
      including the accumulation of metal ions in the plaques and an increase of iron
      in the cortex, have been well documented but the mechanisms involved are poorly
      understood. OBJECTIVE: In this study, we compared the metal content in the
      plaques and the iron speciation in the cortex of three mouse models, two of which
      show neurodegeneration (5xFAD and Tg-SwDI/NOS2-/- (CVN) and one that shows very
      little neurodegeneration (PSAPP). METHODS: The Fe, Cu, and Zn contents and
      speciation were determined using synchrotron X-ray fluorescence microscopy (XFM)
      and X-ray absorption spectroscopy (XAS), respectively. RESULTS: In the mouse
      models with reported significant neurodegeneration, we found that plaques
      contained ~25% more copper compared to the PSAPP mice. The iron content in the
      cortex increased at the late stage of the disease in all mouse models, but iron
      speciation remains unchanged. CONCLUSIONS: The elevation of copper in the plaques
      and iron in the cortex is associated with AD severity, suggesting that these
      redox-active metal ions may be inducing oxidative damage and directly influencing
      neurodegeneration.

PMID- 24926427
TI  - Are the data on quality of life and patient reported outcomes from clinical
      trials of metastatic non-small-cell lung cancer important?
AB  - Majority of the patients with advanced non-small-cell lung cancer (NSCLC)
      experience two or more disease related symptoms, which may have a negative impact
      on their health-related quality of life (HR QOL). These patients prefer a therapy
      that would improve disease related symptoms, as opposed or treatment that
      slightly prolongs their survival without improving symptoms. The improvements of
      the symptoms augment the significance of improved response rates or progression
      free survivals. The choice of the questionnaires to evaluate patients-reported
      outcomes (PROs) and HRQOL benefits and methods of collecting the data and their
      interpretations are very important and are discussed in this manuscript. PROs and
      HR QOL outcomes are important in patients with advanced NSCLC only when the data
      are collected and analyzed correctly. Then they can be viewed as components of
      the total value of a treatment, providing a comprehensive picture of the benefits
      and risks of anticancer therapies. Enabling the patients to feel during the last
      months of their lives more comfortable and not be dependent on their loved ones
      is a very important task in the treatment of advanced NSCLC. 

PMID- 24926426
TI  - Sumoylation and the DNA damage response.
AB  - The cellular response to DNA damage involves multiple pathways that work together
      to promote survival in the face of increased genotoxic lesions. Proteins in these
      pathways are often posttranslationally modified, either by small groups such as
      phosphate, or by protein modifiers such as ubiquitin or SUMO. The recent
      discovery of many more SUMO substrates that are modified at higher levels in
      damage conditions adds weight to the accumulated evidence suggesting that
      sumoylation plays an important functional role in the DNA damage response. Here
      we discuss the significance of DNA damage-induced sumoylation, the effects of
      sumoylation on repair proteins, sumoylation dynamics, and crosstalk with other
      posttranslational modifications in the DNA damage response. 

PMID- 24926428
TI  - Squamous cell carcinoma of the skin: Emerging need for novel biomarkers.
AB  - The incidence of non-melanoma skin cancers (NMSC) is rising worldwide resulting
      in demand for clinically useful prognostic biomarkers for these malignant tumors,
      especially for invasive and metastatic cutaneous squamous cell carcinoma (cSCC).
      Important risk factors for the development and progression of cSCC include
      ultraviolet radiation, chronic skin ulcers and immunosuppression. Due to the role
      of cumulative long-term sun exposure, cSCC is usually a disease of the elderly,
      but the incidence is also growing in younger individuals due to increased
      recreational exposure to sunlight. Although clinical diagnosis of cSCC is usually
      easy and treatment with surgical excision curable, it is responsible for the
      majority of NMSC related deaths. Clinicians treating skin cancer patients are
      aware that certain cSCCs grow rapidly and metastasize, but the underlying
      molecular mechanisms responsible for the aggressive progression of a
      subpopulation of cSCCs remain incompletely understood. Recently, new molecular
      markers for progression of cSCC have been identified. 

PMID- 24926429
TI  - Monitoring adenoviral based gene delivery in rat glioma by molecular imaging.
AB  - AIM: To determine whether endothelial progenitor cells (EPCs) can be used as
      delivery vehicle for adenoviral vectors and imaging probes for gene therapy in
      glioblastoma. METHODS: To use cord blood derived EPCs as delivery vehicle for
      adenoviral vectors and imaging probes for glioma gene therapy, a rat model of
      human glioma was made by implanting U251 cells orthotopically. EPCs were
      transfected with an adenovirus (AD5/carrying hNIS gene) and labeled with iron
      oxide and inoculated them directly into the tumor 14 d following implantation of
      U251 cells. Magnetic resonance imaging (MRI) was used to in vivo track the
      migration of EPCs in the tumor. The expression of gene products was determined by
      in vivo Tc-99m single photon emission computed tomography (SPECT). The findings
      were validated with immunohistochemistry (IHC). RESULTS: EPCs were successfully
      transfected with the adenoviral vectors carrying hNIS which was proved by
      significantly (P < 0.05) higher uptake of Tc-99m in transfected cells. Viability
      of EPCs following transfection and iron labeling was not altered. In vivo imaging
      showed the presence of iron positive cells and the expression of transgene (hNIS)
      product on MRI and SPECT, respectively, all over the tumors following
      administration of transfected and iron labeled EPCs in the tumors. IHC confirmed
      the distribution of EPC around the tumor away from the injection site and also
      showed transgene expression in the tumor. The results indicated the EPCs' ability
      to deliver adenoviral vectors into the glioma upon intratumor injection.
      CONCLUSION: EPCs can be used as vehicle to deliver adenoviral vector to glioma
      and also act as imaging probe at the same time.

PMID- 24926430
TI  - Pulmonary artery sarcoma successfully treated by right pneumonectomy after
      definitive diagnosis.
AB  - Pulmonary artery sarcoma (PAS) is a rare and lethal neoplasm that is usually
      diagnosed during surgery or autopsy. Early diagnosis and radical surgical
      resection offer the only chance for survival. However, making a preoperative
      histopathological diagnosis is quite difficult. We encountered a 57-year-old
      woman presenting a PAS that mimicked a pulmonary thromboembolism. After
      confirming a definitive diagnosis using a catheter suction biopsy, we
      successfully performed a right pneumonectomy via a median sternotomy without
      cardiopulmonary bypass. Eighteen months after surgery, no recurrence was
      observed. 

PMID- 24926431
TI  - The Epicardium and the Development of the Atrioventricular Junction in the Murine
      Heart.
AB  - Insight into the role of the epicardium in cardiac development and regeneration
      has significantly improved over the past ten years. This is mainly due to the
      increasing availability of new mouse models for the study of the epicardial
      lineage. Here we focus on the growing understanding of the significance of the
      epicardium and epicardially-derived cells in the formation of the
      atrioventricular (AV) junction. First, through the process of epicardial
      epithelial-to-mesenchymal transformation (epiEMT), the subepicardial AV
      mesenchyme is formed. Subsequently, the AV-epicardium and epicardially-derived
      cells (EPDCs) form the annulus fibrosus, a structure important for the electrical
      separation of atrial and ventricular myocardium. Finally, the AV-EPDCs
      preferentially migrate into the parietal AV valve leaflets, largely replacing the
      endocardially-derived cell population. In this review, we provide an overview of
      what is currently known about the regulation of the events involved in this
      process.

PMID- 24926432
TI  - The Epicardium in the Embryonic and Adult Zebrafish.
AB  - The epicardium is the mesothelial outer layer of the vertebrate heart. It plays
      an important role during cardiac development by, among other functions,
      nourishing the underlying myocardium, contributing to cardiac fibroblasts and
      giving rise to the coronary vasculature. The epicardium also exerts key functions
      during injury responses in the adult and contributes to cardiac repair. In this
      article, we review current knowledge on the cellular and molecular mechanisms
      underlying epicardium formation in the zebrafish, a teleost fish, which is
      rapidly gaining status as an animal model in cardiovascular research, and compare
      it with the mechanisms described in other vertebrate models. We moreover describe
      the expression patterns of a subset of available zebrafish Wilms' tumor 1
      transgenic reporter lines and discuss their specificity, applicability and
      limitations in the study of epicardium formation.

PMID- 24926433
TI  - Shared and unique proteins in human, mouse and rat saliva proteomes: Footprints
      of functional adaptation.
AB  - The overall goal of our study was to compare the proteins found in the saliva
      proteomes of three mammals: human, mouse and rat. Our first objective was to
      compare two human proteomes with very different analysis depths. The 89 shared
      proteins in this comparison apparently represent a core of highly-expressed human
      salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack
      signal peptides and probably are contaminants instead of less highly-represented
      salivary proteins. We recently published the first rodent saliva proteomes with
      salivas collected from the genome mouse (C57BL/6) and the genome rat
      (BN/SsNHsd/Mcwi). Our second objective was to compare the proteins in the human
      proteome with those we identified in the genome mouse and rat to determine those
      common to all three mammals as well as the specialized rodent subset. We also
      identified proteins unique to each of the three mammals because differences in
      the secreted protein constitutions can provide clues to differences in the
      evolutionary adaptation of the secretions in the three different mammals.

PMID- 24926435
TI  - Analysis of extracellular RNA by digital PCR.
AB  - The transfer of extracellular RNA is emerging as an important mechanism for inter
      cellular communication. The ability for the transfer of functionally active RNA
      molecules from one cell to another within vesicles such as exosomes enables a
      cell to modulate cellular signaling and biological processes within recipient
      cells. The study of extracellular RNA requires sensitive methods for the
      detection of these molecules. In this methods article, we will describe protocols
      for the detection of such extracellular RNA using sensitive detection
      technologies such as digital PCR. These protocols should be valuable to
      researchers interested in the role and contribution of extracellular RNA to tumor
      cell biology. 

PMID- 24926434
TI  - Constraining the Pluripotent Fate of Human Embryonic Stem Cells for Tissue
      Engineering and Cell Therapy - The Turning Point of Cell-Based Regenerative
      Medicine.
AB  - To date, the lack of a clinically-suitable source of engraftable human
      stem/progenitor cells with adequate neurogenic potential has been the major
      setback in developing safe and effective cell-based therapies for regenerating
      the damaged or lost CNS structure and circuitry in a wide range of neurological
      disorders. Similarly, the lack of a clinically-suitable human cardiomyocyte
      source with adequate myocardium regenerative potential has been the major setback
      in regenerating the damaged human heart. Given the limited capacity of the CNS
      and heart for self-repair, there is a large unmet healthcare need to develop stem
      cell therapies to provide optimal regeneration and reconstruction treatment
      options to restore normal tissues and function. Derivation of human embryonic
      stem cells (hESCs) provides a powerful in vitro model system to investigate
      molecular controls in human embryogenesis as well as an unlimited source to
      generate the diversity of human somatic cell types for regenerative medicine.
      However, realizing the developmental and therapeutic potential of hESC
      derivatives has been hindered by the inefficiency and instability of generating
      clinically-relevant functional cells from pluripotent cells through conventional
      uncontrollable and incomplete multi-lineage differentiation. Recent advances and
      breakthroughs in hESC research have overcome some major obstacles in bringing
      hESC therapy derivatives towards clinical applications, including establishing
      defined culture systems for de novo derivation and maintenance of clinical-grade
      pluripotent hESCs and lineage-specific differentiation of pluripotent hESCs by
      small molecule induction. Retinoic acid was identified as sufficient to induce
      the specification of neuroectoderm direct from the pluripotent state of hESCs and
      trigger a cascade of neuronal lineage-specific progression to human neuronal
      progenitors and neurons of the developing CNS in high efficiency, purity, and
      neuronal lineage specificity by promoting nuclear translocation of the neuronal
      specific transcription factor Nurr-1. Similarly, nicotinamide was rendered
      sufficient to induce the specification of cardiomesoderm direct from the
      pluripotent state of hESCs by promoting the expression of the earliest cardiac
      specific transcription factor Csx/Nkx2.5 and triggering progression to cardiac
      precursors and beating cardiomyocytes with high efficiency. This technology
      breakthrough enables direct conversion of pluripotent hESCs into a large supply
      of high purity neuronal cells or heart muscle cells with adequate capacity to
      regenerate CNS neurons and contractile heart muscles for developing safe and
      effective stem cell therapies. Transforming pluripotent hESCs into fate
      restricted therapy derivatives dramatically increases the clinical efficacy of
      graft-dependent repair and safety of hESC-derived cellular products. Such
      milestone advances and medical innovations in hESC research allow generation of a
      large supply of clinical-grade hESC therapy derivatives targeting for major
      health problems, bringing cell-based regenerative medicine to a turning point.

PMID- 24926436
TI  - microRNAs: The Short Link between Cancer and RT-Induced DNA Damage Response.

PMID- 24926437
TI  - How Informative is the Immune Response Against Surrogate Tumor Antigens to Assess
      Antitumor Immunity?

PMID- 24926438
TI  - Visual impairment due to bilateral multifocal choroidal metastasis of parotid
      adenocarcinoma: a case report.
AB  - BACKGROUND: Orbital metastases are an uncommon finding, being present in just 9%
      deceased patients with metastatic cancer. Only a quarter of patients with
      choroidal metastases have bilateral disease. Parotid cancer is not a common form
      of head and neck malignancy. Bilateral multifocal metastases from adenocarcinoma
      ex pleomorphic of parotid gland have been documented just once before in the
      literature. We present a similar case where palliative EBRT was used to gain
      local control with minimal toxicity. CASE PRESENTATION: The case of a 45-year-old
      Caucasian gentleman who presented to his general practitioner with otalgia and
      weight loss. Imaging revealed a mass in the deep lobe of the left parotid gland,
      invading into the medial pterygoid muscle. PET-CT revealed locoregional and
      distant lymphatic involvement plus disseminated skeletal metastases. Lymph node
      examination revealed adenocarcinoma ex pleomorphic histology. Within weeks of
      this diagnosis, the patient developed rapidly progressive visual impairment.
      Ophthalmologists found multifocal uveal masses bilaterally. Palliative fractions
      of external beam radiotherapy were delivered to the orbits before combination
      chemotherapy. We discuss the patient's presentation, histopathology, and
      management, with support from the literature regarding applied and related
      therapies. SUMMARY: In this rare presentation of disseminated malignancy
      affecting the choroid bilaterally, the authors demonstrate the application of
      palliative EBRT to good local effect. Given the nature of this treatment and that
      of the metastases, in the setting of incurable disease orbital morbidity is
      likely to occur again before the patient's death. Awareness of the initial
      symptoms is important to provide prompt care and maintain quality of life.

PMID- 24926439
TI  - Cancer-selective induction of apoptosis by leczyme.
AB  - Sialic acid-binding lectin (SBL) is a multi-functional protein that is isolated
      from oocytes of Rana catesbeiana. It has both lectin and ribonuclease (enzyme)
      properties, and therefore is called leczyme. We examined the anti-tumor effects
      of SBL and discovered that SBL has potential as a new type of anti-cancer drug.
      SBL causes a cancer-selective induction of apoptosis by multiple signaling
      pathways whereby RNA is its target. It is suggested that the mitochondrial
      pathway and endoplasmic reticulum stress-mediated pathway participate in SBL
      induced signaling. The synergistic anti-tumor effects with other molecules, such
      as tumor necrosis factor-related apoptosis ligand and interferon gamma, have been
      reported. In this study, we summarize the effects of SBL and focus on its cancer
      selective apoptotic properties. In addition, we present a possible explanation
      for its cancer specificity. 

PMID- 24926440
TI  - Stressing mitosis to death.
AB  - The final stage of cell division (mitosis), involves the compaction of the
      duplicated genome into chromatid pairs. Each pair is captured by microtubules
      emanating from opposite spindle poles, aligned at the metaphase plate, and then
      faithfully segregated to form two identical daughter cells. Chromatids that are
      not correctly attached to the spindle are detected by the constitutively active
      spindle assembly checkpoint (SAC). Any stress that prevents correct bipolar
      spindle attachment, blocks the satisfaction of the SAC, and induces a prolonged
      mitotic arrest, providing the cell time to obtain attachment and complete
      segregation correctly. Unfortunately, during mitosis repairing damage is not
      generally possible due to the compaction of DNA into chromosomes, and subsequent
      suppression of gene transcription and translation. Therefore, in the presence of
      significant damage cell death is instigated to ensure that genomic stability is
      maintained. While most stresses lead to an arrest in mitosis, some promote
      premature mitotic exit, allowing cells to bypass mitotic cell death. This mini
      review will focus on the effects and outcomes that common stresses have on
      mitosis, and how this impacts on the efficacy of mitotic chemotherapies. 

PMID- 24926441
TI  - Emergence of Ixodes scapularis and Borrelia burgdorferi, the Lyme disease vector
      and agent, in Ohio.
AB  - Lyme disease, the most common vector-borne disease in the United States, is
      caused by a tick-borne infection with Borrelia burgdorferi. Currently, Ohio is
      considered by the Centers for Disease Control and Prevention (CDC) to be non
      endemic for Lyme disease. The low incidence of Lyme disease in this state was
      largely attributed to the absence of the transmitting vector, Ixodes scapularis,
      commonly known as the blacklegged tick. However, a tick surveillance program
      established by Ohio Department of Health indicated that the number of I.
      scapularis in Ohio had increased sharply in recent years, from 0 - 5 ticks per
      year during 1983-2008 to 15 in 2009, 40 in 2010, and 184 in 2011. During the fall
      deer hunting season, examination of deer heads submitted to Ohio Department of
      Agriculture found 29 I. scapularis from 7 counties in 2010 and 1,830 from 25
      counties in 2011. As of 2012, the tick had been found in 57 of the 88 counties of
      Ohio. In addition, all three active stages (larva, nymph, and adult) of I.
      scapularis were found in Tiverton Township of Coshocton County, demonstrating the
      presence of established tick populations at this central Ohio location. Of 530
      nymphal or adult I. scapularis analyzed by quantitative polymerase chain reaction
      (qPCR), 32 (6.1%) tested positive for the B. burgdorferi flaB gene, ranging from
      36 to 390,000 copies per tick. Antibodies to B. burgdorferi antigens were
      detected in 2 of 10 (20%) field-captured Peromyscus leucopus from Tiverton
      Township, and in 41 of 355 (11.5%) dogs residing in Ohio. Collectively, these
      data suggest that the enzootic life cycle of B. burgdorferi has become
      established in Ohio, which poses risk of Lyme disease to people and animals in
      the area. 

PMID- 24926442
TI  - Forward genetic approaches for elucidation of novel regulators of Lyme arthritis
      severity.
AB  - Patients experiencing natural infection with Borrelia burgdorferi display a
      spectrum of associated symptoms and severity, strongly implicating the impact of
      genetically determined host factors in the pathogenesis of Lyme disease. Herein,
      we provide a summary of the host genetic factors that have been demonstrated to
      influence the severity and chronicity of Lyme arthritis symptoms, and a review of
      the resources available, current progress, and added value of a forward genetic
      approach for identification of novel genetic regulators. 

PMID- 24926443
TI  - Atherosclerotic Cardiovascular Disease Risk and Evidence-based Management of
      Cholesterol.
AB  - An elevated level of low-density lipoprotein cholesterol is directly associated
      with development of atherosclerotic cardiovascular disease, which may present as
      coronary heart disease, stroke, and peripheral arterial disease. The new
      cholesterol management guidelines from the American College of Cardiology and the
      American Heart Association aim to address a comprehensive approach to prevent and
      reduce the risk of atherosclerotic cardiovascular disease. The new guidelines
      recommend initiation of heart healthy lifestyle modifications and 3-hydroxy-3
      methylglutaryl coenzyme-A reductase inhibitor ("statin") therapy in individuals
      who are at a high risk for atherosclerotic cardiovascular disease. It is
      estimated that these guidelines could result in "statin" therapy for one in every
      three adults in the United States. This article presents a review of the current
      cholesterol management guidelines, recommendations from relevant randomized
      controlled trials and meta-analyses obtained from the searches in Medline/PubMed
      and Cochrane Database of Systematic Reviews, and publications from the Centers
      for Disease Control and Prevention, the Centers for Medicare and Medicaid
      Service, and the United States Preventive Services Task Force. 

PMID- 24926445
TI  - Modified off-midline closure of pilonidal sinus disease.
AB  - BACKGROUND: Numerous surgical procedures have been described for pilonidal sinus
      disease, but treatment failure and disease recurrence are frequent. Conventional
      off-midline flap closures have relatively favorable surgical outcomes, but
      relatively unfavorable cosmetic outcomes. AIM: The author reported outcomes of a
      new simplified off-midline technique for closure of the defect after complete
      excision of the sinus tracts. PATIENTS AND METHODS: Two hundred patients of both
      sexes were enrolled for modified D-shaped excisions were used to include all
      sinuses and their ramifications, with a simplified procedure to close the defect.
      RESULTS: The overall wound infection rate was 12%, (12.2% for males and 11.1% for
      females). Wound disruption was necessitating laying the whole wound open and
      management as open technique. The overall wound disruption rate was 6%, (6.1% for
      males and 5.5% for females) and the overall recurrence rate was 7%. CONCLUSION:
      Our simplified off-midline closure without flap appeared to be comparable to
      conventional off-midline closure with flap, in terms of wound infection, wound
      dehiscence, and recurrence. Advantages of the simplified procedure include
      potentially reduced surgery complexity, reduced surgery time, and improved
      cosmetic outcome.

PMID- 24926444
TI  - Scientific evidence-based effects of hydrotherapy on various systems of the body.
AB  - The use of water for various treatments (hydrotherapy) is probably as old as
      mankind. Hydrotherapy is one of the basic methods of treatment widely used in the
      system of natural medicine, which is also called as water therapy, aquatic
      therapy, pool therapy, and balneotherapy. Use of water in various forms and in
      various temperatures can produce different effects on different system of the
      body. Many studies/reviews reported the effects of hydrotherapy only on very few
      systems and there is lack of studies/reviews in reporting the evidence-based
      effects of hydrotherapy on various systems. We performed PubMed and PubMed
      central search to review relevant articles in English literature based on
      "effects of hydrotherapy/balneotherapy" on various systems of the body. Based on
      the available literature this review suggests that the hydrotherapy has a
      scientific evidence-based effect on various systems of the body. 

PMID- 24926446
TI  - The impact of the 2008-2009 economic recession on acute myocardial infarction
      occurrences in various socioeconomic areas of raritan bay region, new jersey.
AB  - BACKGROUND: Psychosocial stress is one important risk factor for myocardial
      infarction. AIM: The study was to assess the impact of the 2008-2009 economic
      recession on myocardial infarction occurrences in different socioeconomic areas
      of Raritan Bay region, New Jersey. MATERIALS AND METHODS: The patients, who were
      treated for acute myocardial infarction from January 2006 to June 2012, were
      grouped based on the average incomes of their residence districts in the Raritan
      Bay region. The Spearman Rank Correlation test was used to assess the correlation
      between the monthly occurrences of myocardial infarction and Dow Jones stock
      averages, as well as the correlation between the myocardial infarction
      occurrences and NJ State unemployment rates. RESULTS: Among 1,491 cases that were
      identified, 990 cases resided in areas with income below the state average and
      477 were from areas above the average. After the onset of the recession, the
      myocardial infarction occurrences trended up in the low-income area group but not
      in the high-income area group; and this increasing trend is correlated with the
      rise in NJ State unemployment rates but not with the changes in stock averages.
      CONCLUSION: Our findings suggest that unemployment contributed to an increased
      risk of myocardial infarction among the residents in low socioeconomic areas
      after the 2008-2009 economic recession.

PMID- 24926447
TI  - Preoperative Diagnosis of Tubular Adenoma of Breast - 10 years of experience.
AB  - BACKGROUND: Tubular adenomas are rare benign neoplasms of female breast affecting
      women, predominantly of child-bearing age group. Definitive diagnosis of this
      tumor is usually achieved after histopathological study. Clinical, radiological,
      and even cytological features are often insufficient for accurate diagnosis. AIM:
      The aim of the present study was planned to analyze clinical and radiological
      features of histologically confirmed cases of tubular adenoma of breast to find
      out a clue for accurate preoperative cytological diagnosis. MATERIALS AND
      METHODS: In our 10-year research program, all histologically confirmed tubular
      adenoma cases of breast were studied. Clinico-radio-cytological features, if
      available, were analyzed and tabulated. RESULTS: Thirty-three cases of tubular
      adenoma of breast were studied. Radiological and cytological assessments are
      available for 12 and 26 cases, respectively. Tubular adenoma could be diagnosed
      in only two cases (7.7%) by cytological assessment, but in none by radiological
      assessment. CONCLUSIONS: Clinico-cyto-radiological assessment could identify the
      benign nature of the tumors in most cases, but final confirmation was possible
      only after histopathological study.

PMID- 24926448
TI  - Types and Frequency of Errors during Different Phases of Testing At a Clinical
      Medical Laboratory of a Teaching Hospital in Tehran, Iran.
AB  - BACKGROUND: According to official data, 60-70% of clinical decisions about
      hospitalization and discharge are based on laboratory results. AIMS: The
      objective of this study is to examine the frequency of errors before, during, and
      after analysis in a major medical laboratory. MATERIALS AND METHODS: This
      descriptive, cross-sectional study was conducted throughout 2012 (January
      December 2012). Errors are recorded by the Quality Control Committee in a
      specially designed record. RESULTS: A total of 303,866 samples, 2,430,928 tests
      were received for analysis. The total number of errors was 153,148 (6.3%)
      (116,392 for inpatients and 36,756 for outpatients). Analysis of the results
      revealed that about 65.09% of the errors occur across preanalytical phase,
      whereas 23.2% and 11.68% are related to analytical and postanalytical phase,
      respectively. CONCLUSION: More than half of the laboratory errors are related to
      preanalytical phase; therefore, proper training and knowledge of intervening
      factors are essential for reducing errors and optimizing the quality.

PMID- 24926449
TI  - The journey toward quality and patient safety in laboratory medicine continues.

PMID- 24926450
TI  - DNA extraction from nocardia species for special genes analysis using PCR.
AB  - BACKGROUND: Nocardia species have a complex cell wall structure similar to that
      of mycobacteria, and the extraction of DNA from this bacterium is extremely
      difficult. Currently, to identify Nocardia species particularly, it is essential
      to utilize molecular techniques. AIMS: In the present study, we investigated STET
      (sodium chloride-TRIS-EDTA-triton) buffer for the extraction of high-quality
      genomic DNA from 20 clinical and environmental isolates. MATERIALS AND METHODS:
      The extracted DNA was evaluated for portion of the 16S rRNA, 65-kDa heat-shock
      protein and 16S rRNA genes via polymerase chain reaction. RESULTS: The extracted
      DNA had high molecular mass, and its concentration and purity was suitable when
      tested in 1% agarose gel, and using UV spectrophotometry. Amplification of three
      different genes was successfully performed. CONCLUSION: This paper reveals an
      inexpensive, reproducible and efficient method of DNA extraction from Nocardia
      species, which is appropriate for accurate identification of this bacterium via
      polymerase chain reaction and polymerase chain reaction-restriction fragment
      length polymorphism.

PMID- 24926451
TI  - Spontaneous renal artery thrombosis: an unusual cause of acute abdomen.
AB  - CONTEXT: Spontaneous thrombosis of renal artery is extremely rare. Its
      presentation is that of commonly encountered problem of acute abdomen
      underscoring the need for a clinician to be aware of it. CASE REPORT: We report a
      case of a 56-year-old male with no previous health problems presented with
      complaint of abdominal pain and nausea. Computed tomography angiogram (CTA) of
      the abdomen and pelvis confirmed thrombus in left renal artery. He showed good
      response to the treatment with resolution of the thrombus and improvement in the
      renal perfusion. CONCLUSION: Our case does conform to the others experience of
      good outcome when treatment is initiated in a timely manner. This patient had
      resolution of symptoms and restoration of perfusion with anticoagulation. The
      purpose of this case report is to remind busy practicing physicians to keep
      spontaneous renal thromboembolism in differential diagnosis in a patient with
      acute abdomen.

PMID- 24926452
TI  - Idiopathic retroperitoneal fibrosis: a challenging case in a rare disease.
AB  - CONTEXT: Retroperitoneal fibrosis is a rare but severe disease. The diagnosis is
      usually late when a patient is evaluated for renal insufficiency. Untreated cases
      may develop serious complications or advance to end-stage renal disease. CASE
      REPORT: We report a 66-year-old man who presented with worsening kidney function.
      He was successfully given the diagnosis of idiopathic retroperitoneal fibrosis.
      Prednisone (1 mg/kg per day) was initiated. The patient's symptoms continued to
      improve at 1 month with stable kidney function. CONCLUSION: Clinicians should
      have high index of suspicion for retroperitoneal fibrosis when patients present
      with an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
      and renal insufficiency from obstructive uropathy. The diagnosis of
      retroperitoneal fibrosis is primarily made from imaging by computed tomography
      (CT) scan. Biopsy should be performed in patients who do not have typical
      findings on CT scan and to exclude the possibility of immunoglobulin G4 (IgG4)
      related disease.

PMID- 24926453
TI  - Determining patient preferences in using social media.

PMID- 24926454
TI  - A study of the use of carbamazepine, pregabalin and alpha lipoic acid in patients
      of diabetic neuropathy.
AB  - BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common, symptomatic, long
      term complication of diabetes mellitus. Many of the agents used to treat DN have
      not been compared with each other. This study was, therefore, undertaken to
      compare the efficacy and safety of carbamazepine, pregabalin and alpha-lipoic
      acid in diabetic neuropathy patients. METHODS: This was a prospective,
      observational study. The patients were categorized into three groups, Group I
      included those patients who were prescribed carbamazepine while group II included
      those on pregabalin and group III patients received alpha-lipoic acid. Each
      patient was followed up at every month for total duration of 6 months.
      Demographic details, presenting symptoms, history of diabetes, laboratory values
      pertaining to diabetes (Fasting blood sugar, Post prandial blood sugar and HbA1c)
      were recorded. Intensity of pain, using a visual analogue scale (VAS), diabetic
      neuropathy symptom (DNS) score and diabetic neuropathy examination (DNE) score
      were assessed at baseline and then at each monthly follow-up. Nerve conduction
      velocity (NCV) was also measured at baseline and then at the end of 3 and 6
      months. RESULTS: A total of 101 patients were enrolled out of them 96 completed
      the study. Regarding VAS, the number of patients having pain was reduced
      substantially however, the speed and the quantum of this reduction were best in
      group II (pregabalin). Regarding DNS, also group II showed the best response in
      terms of number of patients as well as the speed of improvement. The results also
      imply that the relief from diabetic neuropathy (as per DNE score) is superior
      with pregabalin administration. However, no improvement in NCV was evident in any
      group. CONCLUSION: Results of this study suggest that treatment with pregabalin
      gives faster and better improvement in diabetic neuropathy.

PMID- 24926455
TI  - Anti-amyloid beta to tau - based immunization: Developments in immunotherapy for
      Alzheimer disease.
AB  - Immunotherapy might provide an effective treatment for Alzheimer disease (AD). A
      unique feature of AD immunotherapies is that an immune response against a self
      antigen needs to be elicited without causing adverse autoimmune reactions.
      Current research is focussed on two possible targets in this regard: One is the
      inhibition of accumulation and deposition of Amyloid beta 1-42 (Abeta42), which
      is one of the major peptides found in senile plaques and the second target is
      hyperphosphorylated tau, which forms neurofibrillary tangles inside the nerve
      cell and shows association with the progression of dementia. Mouse models have
      shown that immunotherapy targeting Abeta42 as well as tau with the respective
      anti-Abeta or anti-tau antibodies can provide significant improvements in these
      mice. While anti-Abeta immunotherapy (active and passive immunizations) is
      already in several stages of clinical trials, tau based immunizations have been
      analyzed only in mouse models. Recently, as a significant correlation of
      progression of dementia and levels of phoshorylated tau was found, high interest
      has again focussed on further development of tau based therapies. While Abeta
      immunotherapy might delay the onset of AD, immunotherapy targeting tau might
      provide benefits in later stages of this disease. And last but not least,
      targeting Abeta and tau simultaneously with immunotherapy might provide
      additional therapeutic effects as these two pathologies are likely synergistic;
      an approach which has not been tested yet. In this review, we will summarize
      animal models used to test possible therapies for AD, some of the facts about
      Abeta42 and tau biology, present on overview on halted, ongoing and upcoming
      clinical trials together with ongoing preclinical studies targeting tau or
      Abeta42.

PMID- 24926456
TI  - Growth hormone treatment in non-growth hormone-deficient children.
AB  - Until 1985 growth hormone (GH) was obtained from pituitary extracts, and was
      available in limited amounts only to treat severe growth hormone deficiency
      (GHD). With the availability of unlimited quantities of GH obtained from
      recombinant DNA technology, researchers started to explore new modalities to
      treat GHD children, as well as to treat a number of other non-GHD conditions.
      Although with some differences between different countries, GH treatment is
      indicated in children with Turner syndrome, chronic renal insufficiency, Prader
      Willi syndrome, deletions/mutations of the SHOX gene, as well as in short
      children born small for gestational age and with idiopathic short stature.
      Available data from controlled trials indicate that GH treatment increases adult
      height in patients with Turner syndrome, in patients with chronic renal
      insufficiency, and in short children born small for gestational age. Patients
      with SHOX deficiency seem to respond to treatment similarly to Turner syndrome.
      GH treatment in children with idiopathic short stature produces a modest mean
      increase in adult height but the response in the individual patient is
      unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial
      also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH
      treatment normalizes growth and improves body composition and cognitive function.
      In any indication the response to GH seems correlated to the dose and the
      duration of treatment. GH treatment is generally safe with no major adverse
      effects being recorded in any condition. 

PMID- 24926458
TI  - Serum vitamin D status in children and adolescence with diabetes according to
      season and age.
AB  - PURPOSE: It is known that children with diabetes have more severe vitamin D
      deficiency than healthy children. This study aimed to investigate serum vitamin D
      status and analyze the relationships between serum vitamin D levels and clinical
      parameters in children with diabetes. METHODS: We checked serum vitamin D levels
      of children with diabetes aged below 18 years who were treated at our Department
      of Pediatrics between December 2011 and February 2012 (winter) as well as between
      June 2012 and August 2012 (summer). We retrospectively analyzed relationships
      between their serum vitamin D levels and clinical parameters. RESULTS: The serum
      25-hydroxyvitamin D level in children with diabetes during winter was markedly
      lower than during summer (10.8+/-5.1 ng/mL vs. 17.6+/-5.6 ng/mL); vitamin D
      deficiency was more prevalent during winter (95% vs. 62%). However, there was no
      difference between children with diabetes and healthy children. In children with
      type I diabetes mellitus, among all the clinical parameters, age had the greatest
      negative correlation with serum vitamin D level. CONCLUSION: In children with
      diabetes, serum vitamin D levels showed marked seasonal variation. However, no
      clear relationship was identified between vitamin D deficiency and diabetes. This
      was because the control group had an equally high vitamin D deficiency rate.
      Additional studies including other clinical parameters after vitamin D
      supplementation in children with diabetes should be considered.

PMID- 24926457
TI  - Iodine and thyroid function.
AB  - Severe iodine deficiency causes hypothyroidism that results in impaired somatic
      growth and motor development in children. Mild and moderate iodine deficiencies
      cause multifocal autonomous growth of thyroid, which results in thyrotoxicosis.
      On the other hand, iodine excess is associated with the development of
      hypothyroidism and thyroid autoimmunity. In areas of iodine deficiency, a sudden
      increase in iodine intake is associated with transient hyperthyroidism. Recent
      studies demonstrated that long-term thyroid function of subjects who experienced
      both iodine deficiency and iodine excess during childhood tended to be abnormal
      despite optimization of their current iodine intake. Iodine status in the Korean
      Peninsula is very unique because people in the Republic of Korea have been shown
      to have predominantly excessive iodine levels, whereas the Democratic People's
      Republic of Korea is known to be an iodine-deficient area. Further research is
      warranted to verify the optimal ranges of iodine intake and to clarify the
      effects of iodine intake on thyroid disorders in the Korean Peninsula. 

PMID- 24926459
TI  - Clinical and radiological findings of incidental Rathke's cleft cysts in children
      and adolescents.
AB  - PURPOSE: In the pediatric population, Rathke's cleft cysts (RCCs) are known to be
      an infrequent cause of headaches, visual disturbances, and pituitary dysfunction.
      We investigated the clinical characteristics of children in whom RCCs were
      incidentally discovered and evaluated whether RCCs influence the treatment
      response of patients with proven endocrinopathy. METHODS: A retrospective
      analysis was conducted in 34 patients with RCCs who were diagnosed between 2006
      and 2013 at Hallym University Medical Center. Their clinical, hormonal, and
      imaging findings were reviewed. We evaluated the clinical outcomes of the
      patients with concomitant RCCs and endocrinopathy compared to matched controls.
      RESULTS: Twenty-six of 34 patients with radiologically proven RCCs had endocrine
      disorders. They were 9 boys and 17 girls, with ages ranging from 4.8 to 17.4
      years at the time of the diagnosis. Of these, 7 (27%) had idiopathic short
      stature, 7 (27%) had growth hormone deficiency (GHD), and 12 (46%) had central
      precocious puberty (CPP). Nineteen of 26 patients (73.1%) showed low signal
      intensities on T1-weighted images (T1WI) and high signal intensities on T2
      weighted images. The incidence of hypointensity on T1WI was higher in the
      patients with RCCs accompanied by endocrinopathy than in those without
      endocrinopathy (P=0.033). The treatment outcomes of the patients with CPP and GHD
      with and without RCCs were similar. CONCLUSION: CPP and GHD patients with a small
      RCC (less than 20 mm) expressing cystic magnetic resonance intensity can be
      managed with medical treatment, although the RCCs need to be closely monitored in
      radiological studies to observe their growth.

PMID- 24926460
TI  - Age of menarche and near adult height after long-term gonadotropin-releasing
      hormone agonist treatment in girls with central precocious puberty.
AB  - PURPOSE: Gonadotropin-releasing hormone agonist (GnRHa) is known for improving
      final adult height in patients with central precocious puberty (CPP). This study
      aimed to investigate the age of menarche and near adult height in girls with CPP
      who had been treated with GnRHa. METHODS: In this retrospective study, we
      reviewed the medical records of 71 Korean girls with CPP who had started menarche
      or reached over 13 years of bone age after long-term GnRHa treatment. We
      estimated near adult height using the Bayley-Pinneau method and identified the
      age of menarche in girls with CPP. RESULTS: Mean chronological and bone age at
      menarche were 11.9+/-0.7 and 12.8+/-0.4 years, respectively. The period between
      menarche and the end of treatment was 14.0+/-5.6 months. Posttreatment near adult
      height was 163.8+/-4.7 cm, which was significantly greater than pretreatment
      predicted adult height (158.7+/-4.1 cm). CONCLUSION: GnRHa treatment in girls
      with CPP could improve final adult height and made the age of menarche close to
      that of the general population.

PMID- 24926461
TI  - Efficacy of growth hormone therapy in adults with childhood-onset growth hormone
      deficiency.
AB  - PURPOSE: Growth hormone (GH) plays a key role in the regulation of body
      composition, lipid metabolism, and quality of life in adults with GH deficiency
      (GHD). This study investigated changes in laboratory findings and body
      composition after GH recommencement for adult GHD and analyzed correlation
      between GH interruption period and endocrine or anthropometric parameters.
      METHODS: A total of 45 patients (17 females and 28 males) diagnosed with
      childhood-onset GHD (CO-GHD) were investigated and all patients had organic brain
      lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age
      20.4+/-5.0 years (18.0-32.1 years). Recombinant human GH was administered at a
      dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height,
      body mass index (BMI), serum insulin-like growth factor 1 (IGF-1), serum total
      cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein
      (LDL) cholesterol, and triglyceride levels, were compared between baseline and 12
      months after treatment using paired t-test. In addition, correlation between GH
      interruption period and clinical parameters including BMI, lipid profile, IGF-1,
      and IGFBP-3, was analyzed. RESULTS: Of 45 patients, 33 patients had GH
      interruption period of 4.3+/-3.6 years (0.7-12.5 years). Serum HDL-cholesterol
      level increased significantly, whereas LDL-cholesterol decreased after 1 year of
      GH replacement therapy. However, body weight and BMI showed no significant
      changes after 1 year of GH replacement therapy. There were no significant
      correlations between GH interruption period and lipid profile or anthropometric
      parameters. CONCLUSION: BMI and body weight were not affected by GH replacement.
      However, GH replacement in adults with GHD offers benefits in lipid metabolism.

PMID- 24926462
TI  - A novel de novo mutation within PHEX gene in a young girl with hypophosphatemic
      rickets and review of literature.
AB  - X-linked hypophosphatemia (XLH) is the most common form of familial
      hypophosphatemic rickets and it is caused by loss-of-function mutations in the
      PHEX gene. Recently, a wide variety of PHEX gene defects in XLH have been
      revealed; these include missense mutations, nonsense mutations, splice site
      mutations, insertions, and deletions. Recently, we encountered a 2-year-9-month
      old female with sporadic hypophosphatemic rickets. She underwent osteotomy,
      dental abscess was evident, and there was severe bowing of the legs. A low serum
      phosphorus level in combination with elevated serum alkaline phosphatase activity
      and normal serum calcium is suggestive of hypophosphatemic rickets. PHEX gene
      analysis revealed a splice acceptor site mutation, c.934-1G>T (IVS8(-1)G>T), at
      the intron8 and exon9 junction. To the best of our knowledge, this mutation is
      novel and has not been reported. The results of this study expand and improve our
      understanding of the clinical and molecular characteristics and the global pool
      of patients with sporadic hypophosphatemic rickets. 

PMID- 24926463
TI  - Mosaic Turner syndrome associated with schizophrenia.
AB  - Turner syndrome is a sex-chromosome disorder; occurring in 1 in 2,500 female
      births. There are sporadic few case reports of concomitant Turner syndrome with
      schizophrenia worldwide. Most Turner females had a 45,X monosomy, whereas the
      majority of comorbidity between Turner syndrome and schizophrenia had a mosaic
      karyotype (45,X/46,XX). We present a case of a 21-year-old woman with Turner
      syndrome, mosaic karyotype (45,X/46,XX), showing mental retardation,
      hypothyroidism, and schizophrenia. HOPA gene within Xq13 is related to mental
      retardation, hypothyroidism, and schizophrenia. Our case may be a potential clue
      which supports the hypothesis for involvement of genes on X chromosome in
      development of schizophrenia. Further studies including comorbid cases reports
      are need in order to discern the cause of schizophrenia in patients having Turner
      syndrome. 

PMID- 24926464
TI  - Giant juvenile fibroadenoma of the breast: a case report and brief literature
      review.
AB  - A girl (age, 12 years 11 months) consulted the pediatric endocrinology clinic
      because of a rapidly growing right breast mass over 13 cm observed during the
      preceding 3 months. A surgical excision was performed, and the mass was diagnosed
      as a giant juvenile fibroadenoma. Giant juvenile fibroadenomas are rare, usually
      occurring between 10 and 18 years of age, and characterized by massive and rapid
      enlargement of an encapsulated mass. The etiology is believed to be an end-organ
      hypersensitivity to normal levels of estrogen. We report a case of giant juvenile
      fibroadenoma and present a review of the diagnostic workup and management of a
      large breast tumor during adolescence. 

PMID- 24926465
TI  - Glycogenic hepatopathy in a Korean girl with poorly controlled type 1 diabetes
      mellitus.
AB  - Glycogenic hepatopathy (GH) is a rare complication of type 1 diabetes mellitus.
      We report the case of a 13-year-old diabetic female with poorly controlled blood
      sugar levels who presented with abdominal pain and distention 1 month in
      duration. She exhibited tender hepatomegaly, an elevated lipid profile, and
      elevated serum transaminase levels. Her liver histology was consistent with GH.
      The pathophysiology and/or underlying genetic background of GH remains unclear.
      The optimum treatment for GH is optimal glycemic control, and the prognosis is
      favorable. Clinicians should be aware of the possibility of GH and observe the
      clinical response to optimal glycemic control prior to invasive investigation. 

PMID- 24926466
TI  - Roles of Long Non-Coding RNAs on Tumorigenesis and Glioma Development.
AB  - More than 98% of eukaryotic tanscriptomes are composed of non-coding RNAs with no
      functional protein-coding capacity. Those transcripts also include tens of
      thousands of long non-coding RNAs (lncRNAs) which are emerging as key elements of
      cellular homeostasis, essentially tumorigenesis steps. However, we are only
      beginning to understand the nature and extent of the involvement of lncRNAs on
      tumorigeneis. Here, we highlight recent progresses that have identified a myriad
      of molecular functions on tumorigenesis for several lncRNAs including metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1), prostate cancer associated
      non-coding RNA 1 (PRNCR1), prostate cancer gene expression marker 1 (PCGEM1),
      H19, and homeobox transcript antisense intergenic RNA (HOTAIR), and several new
      lncRNAs for glioma development. Potential therapeutic approaches for the lncRNAs
      in various human diseases are also discussed. 

PMID- 24926467
TI  - Altered histone modifications in gliomas.
AB  - Gliomas are the most frequently occurring primary brain tumors in adults.
      Although they exist in different malignant stages, including histologically
      benign forms and highly aggressive states, most gliomas are clinically
      challenging for neuro-oncologists because of their infiltrative growth patterns
      and inherent relapse tendency with increased malignancy. Once this disease
      reaches the glioblastoma multiforme stage, the prognosis of patients is dismal:
      median survival time is 15 months. Extensive genetic analyses of glial tumors
      have revealed a variety of deregulated genetic pathways involved in DNA repair,
      apoptosis, cell migration/adhesion, and cell cycle. Recently, it has become
      evident that epigenetic alterations may also be an important factor for glioma
      genesis. Of epigenetic marks, histone modification is a key mark that regulates
      gene expression and thus modulates a wide range of cellular processes. In this
      review, I discuss the neuro-oncological significance of altered histone
      modifications and modifiers in glioma patients while briefly overviewing the
      biological roles of histone modifications. 

PMID- 24926469
TI  - Aberrant CpG islands hypermethylation profiles in malignant gliomas.
AB  - BACKGROUND: The authors analyzed whether the promoter hypermethylation of cancer
      related genes was involved in the tumorigenesis of malignant gliomas. METHODS: A
      total of 29 patients received surgery and histologically confirmed to have
      malignant gliomas from January 2000 to December 2006. The promoter methylation
      status of several genes, which were reported to be frequently methylated in
      malignant gliomas, was investigated using methylation-specific polymerase chain
      reaction. RESULTS: All cases of malignant gliomas represented the promoter
      hypermethylation in at least 2 or more genes tested. Of 29 tumors, 28 (96.55%)
      showed concurrent hypermethylation of 3 or more genes. Ras association domain
      family member 1, epithelial cadherin, O-6 methyl guanine DNA methyltransferase,
      thrombospondin 1, p14 and adenomatous polyposis coli were frequently methylated
      in high grade gliomas including glioblastomas, anaplastic astrocytomas, and
      anaplastic oligodendrogliomas. CONCLUSION: Aberrant hypermethylation profile was
      closely related with malignant gliomas suggesting that epigenetic change may play
      a role in the development of malignant gliomas. Two or three target genes may
      provide useful clues to the development of the useful prognostic as well as
      diagnostic assays for malignant gliomas.

PMID- 24926468
TI  - Proteomic Analysis between U87MG and U343MG-A Cell Lines: Searching for Candidate
      Proteins for Glioma Invasion.
AB  - BACKGROUND: To investigate the molecular basis for invasion of malignant gliomas,
      proteomic analysis approach was carried out using two human glioma cell lines,
      U87MG and U343MG-A that demonstrate different motility and invasiveness in in
      vitro experiments. METHODS: High-resolution two-dimensional gel electrophoresis
      and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry
      analysis were performed. RESULTS: Nine distinct protein spots that were
      recognized with significant alteration between the two cell lines. Five of these
      protein spots were up-regulated in U87MG and four were up-regulated in U343MG-A.
      CONCLUSION: Among these proteins, cathepsin D was shown to be one of the
      important proteins which are related with glioma invasion. However, further
      studies are necessary to reveal the exact role and mechanism of cathepsin D in
      glioma invasion.

PMID- 24926470
TI  - Glioblastoma in a patient with neurofibromatosis type 1: a case report and review
      of the literature.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited familial
      tumor syndrome. Benign tumors such as pilocytic astrocytoma, optic glioma make up
      the majority of intracranial neoplasms in patients with NF1. There have only been
      a handful of cases in which adult glioblastoma presented with NF1. A 32-year-old
      male presented with headache and radiological studies showing a high grade intra
      axial tumor. The patient underwent gross total surgical excision and the
      pathology revealed glioblastoma. After the surgery, he received concomitant chemo
      radiotherapy with temozolomide and adjuvant temozolomide chemotherapy. We report
      a NF1 patient who developed glioblastoma and reviewed related articles. 

PMID- 24926471
TI  - Extradural dermoid cyst located in the lateral sphenoid ridge.
AB  - Dermoid cysts are rare congenital tumors that occur primarily at the midline at a
      characteristic intradural location. However, dermoid cysts located at extradural
      and lateral regions have been rarely reported until now. In the present study,
      the authors demonstrate the unusual instance of an intracranial extradural
      dermoid cyst at the lateral sphenoid ridge. A 53-year-old woman admitted because
      of progressive headache and dizziness. The patient had no neurologic deficits,
      and magnetic resonance imaging with no contrast enhancement revealed a mass at
      the right sphenoid ridge. The mass was accompanied with sphenoid bone erosion
      visible on computed tomography. The patient underwent right pterional craniotomy,
      and the tumor including the capsule was totally resected. Presence of a dermoid
      cyst was confirmed with histopathological examination. The patient had no
      complications during the postoperative period. This study suggests that dermoid
      cyst should be considered for differential diagnosis of extradural and lateral
      intracranial masses. 

PMID- 24926472
TI  - Oculomotor nerve schwannoma: a case report.
AB  - Schwannomas account for about 8% of intracranial tumors and 90% are vestibular
      schwannomas. Oculomotor schwannoma without neurofibromatosis is extremely rare. A
      41-year-old female presented with complaints of blurred vision, and the
      neurologic examination revealed afferent pupillary defect and decreased visual
      acuity of the left side. Brain magnetic resonance image showed an extra axial
      mass in the left superior orbital fissure. The patient underwent major surgery
      via the fronto-temporal approach. The tumor originated from the oculomotor nerve
      and was subtotally removed under microscopic surgery. The pathological findings
      confirmed the tumor as a schwannoma. After surgery, ptosis and medial gaze
      limitation of the left eye was detected, but the symptoms improved gradually. 

PMID- 24926473
TI  - Pediatric sleep surgery.
AB  - Adenotonsillectomy is the most common surgery performed for sleep disordered
      breathing with good outcomes. Children with obesity, craniofacial disorders, and
      neurologic impairment are at risk for persistent sleep apnea after
      adenotonsillectomy. Techniques exist to address obstructive lesions of the
      palate, tongue base, or craniofacial skeleton in children with persistent sleep
      apnea. Children with obstructive sleep apnea have a higher rate of peri-operative
      complications. 

PMID- 24926474
TI  - The role of adipose tissue and obesity in causing treatment resistance of acute
      lymphoblastic leukemia.
AB  - Obesity is responsible for ~90,000 cancer deaths/year, increasing cancer
      incidence and impairing its treatment. Obesity has also been shown to impact
      hematological malignancies, through as yet unknown mechanisms. Adipocytes are
      present in bone marrow and the microenvironments of many types of cancer, and
      have been found to promote cancer cell survival. In this review, we explore
      several ways in which obesity might cause leukemia treatment resistance. Obese
      patients may be at a treatment disadvantage due to altered pharmacokinetics of
      chemotherapy and dosage "capping" based on ideal body weight. The adipose tissue
      provides fuel to cancer cells in the form of amino acids and free fatty acids.
      Adipocytes have been shown to cause cancer cells to resist chemotherapy-induced
      apoptosis. In addition, obese adipose tissue is phenotypically altered, producing
      a milieu of pro-inflammatory adipokines and cytokines, some of which have been
      linked to cancer progression. Given the prevalence of obesity, understanding its
      role and adipose tissue in acute lymphoblastic leukemia treatment is necessary
      for evaluating current treatment regimen and revealing new therapeutic targets. 

PMID- 24926475
TI  - Red man syndrome following intraperitoneal vancomycin in a child with
      peritonitis.
AB  - Red man syndrome (RMS) has frequently been reported to occur with intravenous
      vancomycin therapy. However, there have been few reports of this complication
      during intraperitoneal (IP) treatment with vancomycin. This report describes an
      11-year-old boy with end stage renal disease who developed RMS 45 min into the
      initial loading dose of IP vancomycin for the treatment of bacterial peritonitis
      with a vancomycin level of 38.8 mcg/mL. The patient developed this adverse
      reaction despite appropriate initial loading dose per ISPD guidelines for
      continuous treatment (1000 mg/L). This case emphasizes the importance of
      monitoring for adverse reactions of vancomycin therapy, and raises dosing
      considerations that differ slightly from the currently recommended ISPD
      guidelines for IP vancomycin treatment in the treatment of bacterial peritonitis.

PMID- 24926477
TI  - The Prevention of Mental Disorders has a Bright Future.
AB  - This article takes four looks at the status of prevention in psychiatry. The
      first glance is critical, shaped by disappointment at the slow progress in the
      understanding of psychiatric diseases and the lack of promise in prevention. The
      second look is less humble. It characterizes and acknowledges the efforts made so
      far. The third and the fourth perspectives optimistically announce a new age in
      research and prevention. Breakthroughs, whose contours are already appearing on
      the horizon today, will transform the prevention of psychiatric diseases into a
      success story within the next 10-15 years. 

PMID- 24926476
TI  - Exposure to endocrine disrupting chemicals and male reproductive health.
AB  - Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance
      and may exert adverse consequences on humans. The male reproductive system may be
      susceptible to the effects of such environmental toxicants. This review discusses
      the recent progress in scientific data mainly from epidemiology studies on the
      associations between EDCs and male reproductive health and our understanding of
      possible mechanisms associated with the effects of EDCs on male reproductive
      health. Finally, the review provides recommendations on future research to
      enhance our understanding of EDCs and male reproductive health. The review
      highlights the need for (1) well-defined longitudinal epidemiology studies, with
      appropriately designed exposure assessment to determine potential causal
      relationships; (2) chemical and biochemical approaches aimed at a better
      understanding of the mechanism of action of xenoestrogens with regard to low-dose
      effects, and assessment of identify genetic susceptibility factors associated
      with the risk of adverse effects following exposure to EDCs. 

PMID- 24926478
TI  - Developing suitable buffers to capture transport cycling behavior.
AB  - The association between neighborhood built environment and cycling has received
      considerable attention in health literature over the last two decades, but
      different neighborhood definitions have been used and it is unclear which one is
      most appropriate. Administrative or fixed residential spatial units (e.g., home
      buffer-based neighborhoods) are not necessarily representative for environmental
      exposure. An increased understanding of appropriate neighborhoods is needed. GPS
      cycling tracks from 78 participants for 7 days form the basis for the development
      and testing of different neighborhood buffers for transport cycling. The
      percentage of GPS points per square meter was used as indicator of the
      effectiveness of a series of different buffer types, including home-based network
      buffers, shortest route to city center buffers, and city center-directed ellipse
      shaped buffers. The results show that GPS tracks can help us understand where
      people go and stay during the day, which can help us link built environment with
      cycling. Analysis showed that the further people live from the city center, the
      more elongated are their GPS tracks, and the better an ellipse-shaped directional
      buffer captured transport cycling behavior. In conclusion, we argue that in order
      to be able to link built environment factors with different forms of physical
      activity, we must study the most likely area people use. In this particular
      study, to capture transport cycling, with its relatively large radius of action,
      city center-directed ellipse-shaped buffers yielded better results than
      traditional home-based network buffer types. The ellipse-shaped buffer types
      could therefore be considered an alternative to more traditional buffers or
      administrative units in future studies of transport cycling behavior. 

PMID- 24926480
TI  - Anomaly in the electronic structure of the Na(x)CoO(2-y) cathode as a source of
      its step-like discharge curve.
AB  - In this paper we would like to show a new approach to an explanation of the
      nature of the discharge-charge curve of Na/Na(+)/NaxCoO2-y batteries, which can
      justify the existence of the step-like characteristics. This is still an open
      problem, which until now had no proper description in the literature. On the
      basis of comprehensive experimental studies of physicochemical properties of
      NaxCoO2-y cathode material (XRD, electrical conductivity, thermoelectric power,
      electronic specific heat) supported by calculations performed using the DFT
      method with accounting for chemical disorder, it has been shown that the observed
      step-like character of the discharge curve reflects the variation of the chemical
      potential of electrons (Fermi level) in the density of states of NaxCoO2-y, which
      is anomalously perturbed by the presence of the oxygen vacancy defects and sodium
      ordering. Our studies of structural, electronic and thermal properties of NaxCoO2
      y cathode material as a function of concentration of electrochemically
      intercalated sodium document strong and step-like shift of the position of the
      Fermi level during introduction of electrons in this process. This effect is
      coherently supported by the shape of calculated density of states (DOS) of
      NaxCoO2-y having included oxygen defects and sodium ordering. 

PMID- 24926481
TI  - Interfacial mass transfer by controlled multilayer disassembly.
AB  - We demonstrated the one-pot disassembly of self-propagating molecular assemblies
      (SPMAs) by ligand exchange and the subsequent covalent binding of the molecular
      components to other surfaces. These functionalized surfaces are suitable for
      regenerating the SPMAs. 

PMID- 24926482
TI  - Colloidal core-shell materials with 'spiky' surfaces assembled from gold
      nanorods.
AB  - A series of core-shell materials with 'spiky' surfaces are prepared through the
      self-assembly of gold nanorods onto polystyrene microspheres. Loading of the
      nanorods is finely tuned and the assemblies exhibit surface plasmon resonance
      properties. The 'spiky' surface topography of the assembled structures could
      serve as a versatile substrate for surface-enhanced Raman spectroscopy based
      sensing applications. 

PMID- 24926479
TI  - Translational research in agricultural biology-enhancing crop resistivity against
      environmental stress alongside nutritional quality.

PMID- 24926483
TI  - Construction of fused- and spiro-oxa-[n.2.1] skeletons by a tandem epoxide
      rearrangement/intramolecular [3+2] cycloaddition of cyclopropanes with carbonyls.
AB  - A Lewis acid promoted tandem reaction of epoxide rearrangement and intramolecular
      [3+2] cycloaddition reaction of cyclopropanes with carbonyls formed by epoxide
      rearrangement in situ, which were obtained with difficulty by a general method,
      is reported. A wide variety of fused- and spiro-oxa-[n.2.1] skeletons could be
      efficiently constructed. 

PMID- 24926484
TI  - A novel anode material derived from organic-coated ZIF-8 nanocomposites with high
      performance in lithium ion batteries.
AB  - A general method of preparing nanocomposites from a metal-organic framework
      coated with hydroxyl, pyrrolyl and/or carboxyl functionalized organics is
      introduced. Pyrolysis of these nanocomposites gives anode materials with improved
      discharge capacity (750 mA h g(-1)) and cyclability. They also show enhanced
      Coulombic efficiency over the initial 5-10 cycles and decreased internal
      impedance. 

PMID- 24926485
TI  - The prevalence and predictive value of weak language skills in children with 
      very low birth weight--a longitudinal study.
AB  - AIM: Previous findings regarding the prevalence and predictive value of weak
      language skills in preterm children with very low birth weight (VLBW) are
      unclear. This study analysed the prevalence of weak language skills, the
      predictive value of early weak language skills on later weak language skills, and
      the sensitivity and specificity of cognitive scores for identifying concurrent
      weak language skills in a longitudinal sample of VLBW children (n = 141) and
      their full-term controls (n = 146). METHODS: Data on language skills and
      cognitive development were gathered at two and five years of age. Weak language
      skills were defined by the 10th percentile value of the controls. RESULTS: In
      VLBW children, the prevalence of weak language skills varied between 16% and 18%
      at 2 years of age (controls: 8 to 10%) and between 20% and 27% at 5 years of age
      (controls: 10%). Early weak language skills predicted later weak language skills
      in VLBW children. Cognitive scores were specific, but their sensitivity for
      identifying concurrent weak language skills was low. CONCLUSION: The prevalence
      of weak language skills in VLBW children increased during the follow-up period
      and was higher than the controls. Language-sensitive methods should be used in
      the clinical follow-up of VLBW children.

PMID- 24926487
TI  - Keith Edwards.

PMID- 24926488
TI  - Synthesis of a dialumene-benzene adduct and its reactivity as a synthetic
      equivalent of a dialumene.

PMID- 24926489
TI  - Cardiovascular highlights from non-cardiology journals.

PMID- 24926491
TI  - International journal of urology supplement 3rd International Consultation
      Interstitial Cystitis Japan (ICICJ) and International Society for the Study of
      Bladder Pain Syndrome (ESSIC) Joint Meeting 21-23 March 2013 Kyoto, Japan.
      Preface.

PMID- 24926490
TI  - Motor impairment in very preterm-born children: links with other  developmental
      deficits at 5 years of age.
AB  - AIM: To elucidate the relation between motor impairment and other developmental
      deficits in very preterm-born children without disabling cerebral palsy and term
      born comparison children at 5 years of (corrected) age. METHOD: In a prospective
      cohort study, 165 children (81 very preterm-born and 84 term-born)were assessed
      with the Movement Assessment Battery for Children - 2nd edition, Touwen's
      neurological examination, the Wechsler Preschool and Primary Scale of
      Intelligence, processing speed and visuomotor coordination tasks of the Amsterdam
      Neuropsychological Tasks, and the Strengths and Difficulties Questionnaire.
      RESULTS: Motor impairment (<=15th centile) occurred in 32% of the very preterm
      born children compared with 11% of their term-born peers (p=0.001). Of the very
      preterm-born children with motor impairment, 58% had complex minor neurological
      dysfunctions, 54% had low IQ, 69% had slow processing speed, 58% had visuomotor
      coordination problems, and 27%, 50%,and 46% had conduct, emotional, and
      hyperactivity problems respectively. Neurological outcome (odds ratio [OR]=41.7,
      95% confidence intervals [CI] 7.5-232.5) and Full-scale IQ(OR=7.3, 95% CI 1.9
      27.3) were significantly and independently associated with motor impairment.
      Processing speed (OR=4.6, 95% CI 1.8-11.6) and attention (OR=3.2, 95% CI1.3-7.9)
      were additional variables associated with impaired manual dexterity. These four
      developmental deficits mediated the relation between preterm birth and motor
      impairment. INTERPRETATION: Complex minor neurological dysfunctions, low IQ, slow
      processing speed,and hyperactivity/inattention should be taken into account when
      very preterm-born children are referred for motor impairment.

PMID- 24926493
TI  - Carotid stent deformation: sonographic findings and CT correlation.
AB  - Carotid artery dissection is a rare but potentially serious complication of
      endovascular procedures in the carotid arteries. Stent deformation or incomplete
      expansion may occur following endovascular repair of an iatrogenic carotid artery
      dissection and may mimic stent fracture. We report an unusual case of deformation
      of a common carotid artery open cell design stent following endovascular repair
      of an iatrogenic dissection, which resulted in persistent blood flow between the
      stent and the wall of the common carotid artery. Sonographic features are
      described and correlation with intravascular ultrasound and CT is provided.

PMID- 24926494
TI  - Dropped omental fat post laparoscopy-assisted distal gastrectomy with omentectomy
      mistaken for malignant peritoneal seeding on sonography.
AB  - We report the sonographic findings in a case of dropped omental fat post
      laparoscopy-assisted distal gastrectomy with omentectomy for stomach cancer
      mistaken for malignant intraperitoneal seeding. Gray-scale sonography revealed an
      ovoid-shaped hyperechoic mass with central poorly defined hypoechoic portion in
      the right perihepatic space. Color Doppler sonography showed no blood flow within
      the mass. Contrast-enhanced CT scan of the liver revealed an oval-shaped fatty
      mass with a CT number of -100 HU

PMID- 24926495
TI  - Preface to the proceedings of the Workshop on Eosinophils in Allergy and Related
      Diseases 2013.

PMID- 24926492
TI  - ?N-P63alpha and TA-P63alpha exhibit intrinsic differences in transactivation
      specificities that depend on distinct features of DNA target sites.
AB  - TP63 is a member of the TP53 gene family that encodes for up to ten different TA
      and ?N isoforms through alternative promoter usage and alternative splicing.
      Besides being a master regulator of gene expression for squamous epithelial
      proliferation, differentiation and maintenance, P63, through differential
      expression of its isoforms, plays important roles in tumorigenesis. All P63
      isoforms share an immunoglobulin-like folded DNA binding domain responsible for
      binding to sequence-specific response elements (REs), whose overall consensus
      sequence is similar to that of the canonical p53 RE. Using a defined assay in
      yeast, where P63 isoforms and RE sequences are the only variables, and gene
      expression assays in human cell lines, we demonstrated that human TA- and ?N
      P63alpha proteins exhibited differences in transactivation specificity not
      observed with the corresponding P73 or P53 protein isoforms. These differences 1)
      were dependent on specific features of the RE sequence, 2) could be related to
      intrinsic differences in their oligomeric state and cooperative DNA binding, and
      3) appeared to be conserved in evolution. Sicen genotoxic stress can change
      relative ratio of TA- and ?N-P63alpha protein levels, the different
      transactivation specificity of each P63 isoform could potentially influence
      cellular responses to specific stresses.

PMID- 24926496
TI  - Compassion satisfaction, compassion fatigue, anxiety, depression and stress in
      registered nurses in Australia: phase 2 results.
AB  - AIM: This is the first two-phase Australian study to explore the factors
      impacting upon compassion satisfaction, compassion fatigue, anxiety, depression
      and stress and to describe the strategies nurses use to build compassion
      satisfaction into their working lives. BACKGROUND: Compassion fatigue has been
      found to impact on job satisfaction, the quality of patient care and retention
      within nursing. This study provides new knowledge on the influences of anxiety,
      stress and depression and how they relate to compassion satisfaction and
      compassion fatigue. METHOD: In Phase 2 of the study, 10 nurses from Phase 1 of
      the study participated in individual interviews and a focus group. A semi
      structured interview schedule guided the conversations with the participants.
      RESULT: Data analysis resulted in seven main themes: social networks and
      support;infrastructure and support; environment and lifestyle; learning;
      leadership; stress; and suggestions to build psychological wellness in nurses.
      CONCLUSION: Findings suggest that a nurse's capacity to cope is enhanced through
      strong social and collegial support, infrastructure that supports the provision
      of quality nursing care and positive affirmation. These concepts are strongly
      linked to personal resilience. IMPLICATIONS: for nursing management These
      findings support the need for management to develop appropriate interventions to
      build resilience in nurses.

PMID- 24926497
TI  - A growing problem.

PMID- 24926498
TI  - Good practice.

PMID- 24926499
TI  - Open goal.

PMID- 24926500
TI  - Capacity building: Architects of South American science.

PMID- 24926501
TI  - Fellowships: Turning brain drain into brain circulation.

PMID- 24926502
TI  - Potential Bryde's whale (Balaenoptera edeni) calls recorded in the northern Gulf
      of Mexico.
AB  - Several marine autonomous recording units (MARUs) were deployed in northeastern
      Gulf of Mexico from 2010-2012 to study the acoustic ecology of Bryde's whales
      (Balaenoptera edeni) following the Deepwater Horizon oil spill. However, the
      acoustic repertoire of this sub-population is poorly documented, presently
      limiting the efficacy of acoustic monitoring applications. Numerous stereotyped,
      low-frequency signals from a putative biological sound source were found
      throughout the recordings. Sounds fell into three categories distinguished by
      spectral and temporal properties. Multiple calls overlapped temporally on
      individual MARUs, suggesting that multiple sources produced these sounds. The
      basic features are similar to those from other mysticetes, but they differ from
      any previously published sounds. Since Bryde's whales are the most common
      mysticete in the Gulf and have previously been observed within the recording area
      on multiple occasions, it is likely that Bryde's whales are the most probable
      source of these sounds. These results potentially identify a suite of previously
      undocumented calls from Bryde's whales, which could facilitate future passive
      acoustic monitoring efforts to better understand the population dynamics and
      status of this sub-population.

PMID- 24926504
TI  - A comparison of acoustic and visual metrics of sperm whale longline depredation.
AB  - Annual federal stock assessment surveys for Alaskan sablefish also attempt to
      measure sperm whale depredation by quantifying visual evidence of depredation,
      including lip remains and damaged fish. A complementary passive acoustic method
      for quantifying depredation was investigated during the 2011 and 2012 survey
      hauls. A combination of machine-aided and human analysis counted the number of
      distinct "creak" sounds detected on autonomous recorders deployed during the
      survey, emphasizing sounds that are followed by silence ("creak-pauses"), a
      possible indication of prey capture. These raw counts were then adjusted for
      variations in background noise levels between deployments. Both a randomized
      Pearson correlation analysis and a generalized linear model found that noise
      adjusted counts of "creak-pauses" were highly correlated with survey counts of
      lip remains during both years (2012: r(10) = 0.89, p = 1e-3; 2011: r(39) = 0.72,
      p = 4e-3) and somewhat correlated with observed sablefish damage in 2011 [r(39) =
      0.37, p = 0.03], but uncorrelated with other species depredation. The acoustic
      depredation count was anywhere from 10% to 80% higher than the visual counts,
      depending on the survey year and assumptions employed. The results suggest that
      passive acoustics can provide upper bounds on depredation rates; however, the
      observed correlation breaks down whenever three or more whales are present.

PMID- 24926503
TI  - Spatial release from simultaneous echo masking in bat sonar.
AB  - Big brown bats (Eptesicus fuscus) use biosonar to navigate and locate objects in
      their surroundings. During natural foraging, they often encounter echoes returned
      by a target of interest located to the front while other, often stronger, clutter
      echoes are returned from objects, such as vegetation, located to the sides or
      above. Nevertheless, bats behave as if they do not suffer interference from this
      clutter. Using a two-choice delay discrimination procedure, bats were tested for
      the masking effectiveness of clutter echoes on target echoes when the target
      echoes were delivered from the bat's front while clutter echoes were delivered
      from 90 degrees  overhead, a direction of lowpass filtering by the external ears.
      When clutter echoes are presented from the front at the same delay as target
      echoes, detection performance declines and clutter masking occurs. When the
      clutter echoes are presented at the same delay but from overhead, discrimination
      performance is unaffected and no masking occurs. Thus there is masking release
      for simultaneous off-axis lowpass clutter compared to masking by simultaneous
      clutter from the front. The bat's performance for simultaneous target and clutter
      echoes indicates a new role for the mechanism that separates overlapping echoes
      by decomposing the bat's auditory time-frequency representation.

PMID- 24926505
TI  - Responses of free-living coastal pelagic fish to impulsive sounds.
AB  - The behavior of wild, pelagic fish in response to sound playback was observed
      with a sonar/echo sounder. Schools of sprat Sprattus sprattus and mackerel
      Scomber scombrus were examined at a quiet coastal location. The fish were exposed
      to a short sequence of repeated impulsive sounds, simulating the strikes from a
      pile driver, at different sound pressure levels. The incidence of behavioral
      responses increased with increasing sound level. Sprat schools were more likely
      to disperse and mackerel schools more likely to change depth. The sound pressure
      levels to which the fish schools responded on 50% of presentations were 163.2 and
      163.3 dB re 1 MUPa peak-to-peak, and the single strike sound exposure levels were
      135.0 and 142.0 dB re 1 MUPa(2) s, for sprat and mackerel, respectively,
      estimated from dose response curves. For sounds leading to mackerel responses,
      particle velocity levels were also estimated. The method of observation by means
      of a sonar/echo sounder proved successful in examining the behavior of
      unrestrained fish exposed to different sound levels. The technique may allow
      further testing of the relationship between responsiveness, sound level, and
      sound characteristics for different types of man-made sound, for a variety of
      fish species under varied conditions.

PMID- 24926507
TI  - Mythologising.

PMID- 24926506
TI  - A study on Rayleigh wave dispersion in bone according to Mindlin's Form II
      gradient elasticity.
AB  - The classical elasticity cannot effectively describe bone's mechanical behavior
      since only homogeneous media and local stresses are assumed. Additionally, it
      cannot predict the dispersive nature of the Rayleigh wave which has been reported
      in experimental studies and was also demonstrated in a previous computational
      study by adopting Mindlin's Form II gradient elasticity. In this work Mindlin's
      theory is employed to analytically determine the dispersion of Rayleigh waves in
      a strain gradient elastic half-space. An isotropic semi-infinite space is
      considered with properties equal to those of bone and dynamic behavior suffering
      from microstructural effects. Microstructural effects are considered by
      incorporating four intrinsic parameters in the stress analysis. The results are
      presented in the form of group and phase velocity dispersion curves and compared
      with existing computational results and semi-analytical curves calculated for a
      simpler case of Rayleigh waves in dipolar gradient elastic half-spaces.
      Comparisons are also performed with the velocity of the first-order antisymmetric
      mode propagating in a dipolar plate so as to observe the Rayleigh asymptotic
      behavior. It is shown that Mindlin's Form II gradient elasticity can effectively
      describe the dispersive nature of Rayleigh waves. This study could be regarded as
      a step toward the ultrasonic characterization of bone.

PMID- 24926508
TI  - Lorcaserin. In obesity: unacceptable risks.
AB  - Treatment of obesity and overweight is based primarily on dietary measures and
      physical exercise.There are still no drugs with a favourable harm-benefit balance
      in this setting. Lorcaserin, a "selective" 5HT2C serotonin receptor agonist, has
      been refused marketing authorisation in the European Union despite approval in
      the United States. Clinical evaluation of lorcaserin is based on three placebo
      controlled trials, each lasting one year, in a total of about 6000 patients. Two
      trials involved obese patients, and one obese patients with type 2 diabetes. The
      results of these trials are undermined by the large proportion (40% to 50%) of
      patients who were lost to follow-up before the end of the trial. None of the
      trials examined the impact of lorcaserin on the clinical complications of
      obesity. From an average initial weight of about 100 kg, patients taking
      lorcaserin lost only about 3 kg more than those in the placebo groups.The
      patients put on weight again after lorcaserin was discontinued. Adverse effects
      observed in clinical trials were mainly gastrointestinal (dry mouth, nausea) and
      neuropsychiatric (dizziness, fatigue, headache, euphoria). The incidence of
      cardiac valve disorders was higher with lorcaserin than with placebo. These
      trials were too short in duration to exclude a risk of cancer (breast cancer and
      astrocytoma) that was reported in experimental animals. This serotonin agonist is
      metabolised by the liver, creating a risk of multiple drug interactions. In
      practice, lorcaserin has not been shown to prevent complications of obesity or
      even lead to substantial weight loss.There is therefore no justification for
      exposing patients to the risk of adverse effects.

PMID- 24926509
TI  - "Selectivity": an attractive but often misleading notion.

PMID- 24926510
TI  - Tapentadol. Acute or chronic pain: no therapeutic advance.
AB  - The standard opioids for relieving moderate to severe pain are: codeine as a step
      2 analgesic and morphine for step 3. Tapentadol is an opioid similar to tramadol.
      An immediate-release form has been authorised in France for moderate to severe
      acute pain in adults and a sustained-release form for severe chronic pain in
      adults. It has been evaluated in comparative trials in several types of acute
      pain: pain following orthopaedic or gynaecological surgery or tooth extraction,
      and joint pain. These trials were principally designed to show its analgesic
      effect versus placebo.They did not establish the equianalgesic dose ratios of
      tapentadol to codeine, morphine or oxycodone. In chronic pain, one trial compared
      sustained-release tapentadol versus sustained-release morphine, but only
      unconvincing preliminary results are available.The results of other trials versus
      sustained-release oxycodone are unconvincing, because half of the patients were
      lost to follow-up. The known adverse effects of tapentadolare mainly those
      associated with all opioids, including neuropsychiatric disorders and addiction.
      Aggression and serotonin syndrome are possible reactions that require further
      investigation. Gastrointestinal disorders appeared less common with tapentadol
      than with oxycodone, but the data could well be biased due to the use of a
      relative overdose of oxycodone in the trials. In practice, the evaluation of
      tapentadol was not designed to show whether this drug represents a therapeutic
      advance. Its analgesic efficacy remains unclear, and it provokes the adverse
      effects common to all opioids.

PMID- 24926511
TI  - Tenofovir in HIV-infected children. Antiretroviral efficacy, but beware of
      adverse effects on bone and the kidneys.
AB  - Beware of tenofovir-induced kidney and bone disorders. The granule form carries a
      risk of dosing errors and has a particularly strong, unpleasant taste.

PMID- 24926512
TI  - INN common stem; -cept.

PMID- 24926513
TI  - Nicotine replacement products: poisoning in children.
AB  - Nicotine is widely used in smoking cessation aids. They are marketed in many
      forms, including: chewing gum, sublingual tablets, lozenges, transdermal patches,
      cartridges for oral inhalation, and mouth spray. French poison control and toxico
      vigilance centres identified 318 cases of exposure to nicotine replacement
      products in children under the age of 10 years between 2000 and 2010. The
      exposure provoked symptoms in 62 of these children, about two-thirds of whom were
      under the age of 4 years. A U.S. analysis identified 1768 cases of poisoning in
      children under the age of 6 years involving smokeless tobacco products, reported
      between 2006 and 2008.84% of these cases occurred in children under the age of 3
      years. The first signs of nicotine poisoning are gastrointestinal (vomiting,
      diarrhoea), cardiovascular (tachycardia, hypertension) and neuropsychological
      (tremor of the extremities). With higher doses, these effects are rapidly
      followed by loss of consciousness, convulsions or respiratory failure. In
      children, poisoning can occur after ingestion of 1 mg of nicotine per kilogram of
      body weight. A dose of this magnitude is sometimes fatal in adults. Most cases of
      poisoning involving transdermal patches occur when a child finds an unused patch,
      or a used patch that an adult has discarded in a bin without taking proper
      precautions. Sometimes they involve patches that have become detached from an
      adult's skin. In practice, it is important to warn adults using smoking cessation
      aids containing nicotine that these products are dangerous

PMID- 24926514
TI  - The pharmacology of nicotine in brief.

PMID- 24926515
TI  - Gliptins: severe pancreatic and cutaneous disorders.

PMID- 24926516
TI  - Benfluorex: left heart valve disease very common.

PMID- 24926517
TI  - Antiseptics: sometimes the cause of infection.

PMID- 24926518
TI  - Mirtazapine: rhabdomyolysis.

PMID- 24926519
TI  - Antithrombotic and cytotoxic drugs: too often fatal.

PMID- 24926520
TI  - Bleeding associated with uterine leiomyomas. Tailor treatment to the individual
      patient.
AB  - Uterine leiomyomas are benign, often asymptomatic, tumours of the uterus. When
      they are symptomatic, the most frequent symptom is heavy, prolonged menstrual
      bleeding, which stops at menopause. When this blood loss causes iron-deficiency
      anaemia, iron supplementation is justified. Various treatments aimed at reducing
      uterine blood loss are proposed for women with leiomyoma-related bleeding. As of
      late 2013, what is the harm-benefit balance of these treatments? To answer this
      question, we reviewed the available data using the standard Prescrire
      methodology. Hysterectomy (removal of the uterus) is the most radical treatment
      for the clinical manifestations of uterine leiomyomas. Serious complications
      sometimes occur. Nine randomised trials including a total of 1553 patients found
      no advantage in leaving the cervix intact. Randomised trials in about 4500
      patients showed that the vaginal approach is preferable to an open abdominal or
      laparoscopic approach: in particular, it resulted in fewer infections and less
      bleeding. Myomectomy (selective removal of uterine leiomyomas) is another
      surgical option, especially when the patient wishes to preserve her fertility.
      Its evaluation is mainly based on noncomparative case series. As with
      hysterectomy, it exposes patients to the risk of serious complications. Symptoms
      recur in 4% to 27% of cases.The reintervention rate is 4% to 20%. Injections of
      the gonadorelin agonists leuprorelin or triptorelin reduce bleeding associated
      with leiomyomas, according to several randomised trials. They have not been
      demonstrated to reduce the need for transfusion or to facilitate subsequent
      surgery for leiomyomas.The harm-benefit balance of prolonged use of these drugs
      is unfavourable, due to their numerous adverse effects. The oral progesterone
      receptor antagonist ulipristal reduces excessive bleeding, but has not been
      demonstrated to facilitate subsequent surgery.The effects on the endometrium of
      taking ulipristal for more than 3 months are unknown. The progesterone antagonist
      mifepristone reduced bleeding in small randomised trials, but increased the
      incidence of endometrial hyperplasia. The levonorgestrel-releasing intrauterine
      device has mainly been evaluated in non-comparative studies, which suggest that
      it reduces menstrual bleeding in women with leiomyomas. The risk of expulsion of
      the device in women with leiomyomas appears to be about 20%. Its main adverse
      effects are rare cases of acne, depression, headache, weight gain and breast
      tenderness. Very little evaluation data is available on oral progestins in this
      situation. A progestin, such as norethisterone, taken from the 5th to the 26th
      day of the menstrual cycle seems to reduce menstrual blood loss and has a
      contraceptive effect. Oral progestins expose women to an increased risk of venous
      thromboembolism and possibly increase the risk of breast cancer. Their harm
      benefit balance seems less favourable than that of the levonorgestrel-releasing
      intrauterine device. The thrombotic risk associated with tranexamic acid is
      unclear, but deserves serious consideration given the drug's uncertain efficacy.
      In practice, the treatment should be chosen with the patient, based on various
      factors, including severity of symptoms, age, desire to preserve fertility or the
      uterus, characteristics of the leiomyomas, and patient preference. As of late
      2013, when drug treatment is considered useful in postponing surgery or while
      awaiting menopause, the levonorgestrel-releasing intrauterine device is the first
      choice. Oral progestins are another alternative, although their adverse effects
      are unclear when taken for several months. It is better to avoid exposing
      patients to the other available drugs, and to choose iron supplementation for
      women who develop anaemia.

PMID- 24926521
TI  - Uterine artery embolisation: an alternative to surgery?
AB  - According to comparative evaluation in about 900 patients, uterine artery
      embolisation may expose patients to a lower risk of serious complications than
      surgery. But it reduces fertility.

PMID- 24926522
TI  - Drug packaging in 2013: small changes would reap big benefits.
AB  - Drug packaging is important both in protecting and informing patients. Some
      improvements were made in 2013, but many of the products examined by Prescrire
      still had poor-quality or even dangerous packaging. Problem packaging is a major
      concern for patients who are more vulnerable to adverse effects, particularly
      children and pregnant women. Several problems were noted with products intended
      for self-medication (umbrella brands), oral solutions sold with dosing devices,
      and injectable drugs. Looking back at 20 years of Red Cards that Prescrire has
      issued to products with dangerous packaging reveals several improvements, but too
      many dangers persist. Urgent action needs to be taken by regulatory agencies and
      drug companies: patient leaflets must be more explicit with regard to adverse
      effects, especially those of nonsteroidal anti-inflammatory drugs during
      pregnancy; accidental ingestion by children must be prevented; and companies must
      design safer dosing devices. Healthcare professionals and patients must remain
      vigilant and report all packaging issues to the relevant authorities.

PMID- 24926524
TI  - Porous anodic aluminum oxide: anodization and templated synthesis of functional
      nanostructures.

PMID- 24926523
TI  - Prescrire's red cards for drug packaging, 1991-2012: some improvements, but many
      dangers persist.

PMID- 24926525
TI  - Glycemic response of a carbohydrate-protein bar with ewe-goat whey.
AB  - In this study we examined the glycaemic index (GI) and glycaemic load (GL) of a
      functional food product, which contains ewe-goat whey protein and carbohydrates
      in a 1:1 ratio. Nine healthy volunteers, (age, 23.3 +/- 3.9 years; body mass
      index, 24.2 +/- 4.1 kg.m2; body fat %, 18.6 +/- 10.0) randomly consumed either a
      reference food or amount of the test food both with equal carbohydrate content in
      two visits. In each visit, seven blood samples were collected; the first sample
      after an overnight fast and the remaining six at 15, 30, 45, 60, 90 and 120 min
      after the beginning of food consumption. Plasma glucose concentration was
      measured and the GI was determined by calculation of the incremental area under
      the curve. The GL was calculated using the equation: test food GI/100 g available
      carbohydrates per test food serving. The GI of the test food was found to be 5.18
      +/- 3.27, while the GL of one test food serving was 1.09 +/- 0.68. These results
      indicate that the tested product can be classified as a low GI (<55) and low GL
      (<10) food. Given the health benefits of low glycaemic response foods and whey
      protein consumption, the tested food could potentially promote health beyond
      basic nutrition. 

PMID- 24926526
TI  - Are the dietary guidelines for meat, fat, fruit and vegetable consumption
      appropriate for environmental sustainability? A review of the literature.
AB  - This paper reviews the current literature around the environmental impacts of
      dietary recommendations. The focus of the review is on collating evidence
      relating to environmental impacts of the dietary advice found in the World Health
      Organisation guidelines, and environmental impact literature: reducing the
      consumption of fat, reducing the consumption of meat-based protein and animal
      based foods, and increasing the consumption of fruit and vegetables. The
      environmental impact of reducing dietary fat intake is unclear, although reducing
      consumption of the food category of edible fats and oils appears to have little
      impact. However most, but not all, studies support environmental benefits of a
      reduced consumption of animal-based foods and increased consumption of fruit and
      vegetables. In general, it appears that adhering to dietary guidelines reduces
      impact on the environment, but further study is required to examine the
      environmental impacts of animal-based foods, and fruit and vegetable intake in
      depth. 

PMID- 24926527
TI  - Can mitochondrial dysfunction be a predictive factor for oxidative stress in
      patients with obstructive sleep apnea?
AB  - Mitochondrial dysfunction reflects a lifelong cumulative burden of cellular
      damage, and a decrease in mitochondrial DNA (mtDNA) copy number is associated
      with oxidative stress and chronic inflammation. The goal of this study was to
      assess whether mitochondrial dysfunction and a decrease in mtDNA copy number are
      common features of patients with obstructive sleep apnea syndrome (OSA). We
      compared mtDNA copy number between 20 healthy volunteers and 20 patients with OSA
      and investigated whether a significant attenuation of mtDNA copy number was
      observed in genomic DNA isolated from whole blood of OSA patients. Our
      observations lead to the hypothesis that mtDNA copy number is lower in whole
      blood DNA of OSA subjects and might be related to OSA severity, reflecting
      excessive oxidative stress in patients with OSA.

PMID- 24926528
TI  - Cytotoxicity and chemosensitizing activity of amphiphilic poly(glycerol)
      poly(alkylene oxide) block copolymers.
AB  - All polymeric chemosensitizers proposed thus far have a linear poly(ethylene
      glycol) (PEG) hydrophilic block. To testify whether precisely this chemical
      structure and architecture of the hydrophilic block is a prerequisite for
      chemosensitization, we tested a series of novel block copolymers containing a
      hyperbranched polyglycerol segment as a hydrophilic block (PPO-NG copolymers) on
      multi-drug-resistant (MDR) tumor cells in culture. PPO-NG copolymers inhibited
      MDR of three cell lines, indicating that the linear PEG can be substituted for a
      hyperbranched polyglycerol block without loss of the polymers' chemosensitizing
      activity. The extent of MDR reversal increased with the polymers affinity toward
      the cells and the expression level of P-glycoprotein. In contrast with Pluronic
      L61, which increases viability of tumor cells in the absence of drugs, PPO-NG
      chemosensitizers are completely devoid of this property undesired in cancer
      therapy, making them promising candidates for application as novel MDR reversal
      agents. 

PMID- 24926529
TI  - Pulmonary toxicity in a rabbit model of stereotactic lung radiation therapy:
      efficacy of a radioprotector.
AB  - This study aimed to assess the efficacy of the radioprotector amifostine in
      limiting radiation toxicity in a rabbit model of lung stereotactic body radiation
      therapy (SBRT) by correlating contrast-enhanced magnetic resonance angiography
      (ce-MRA), computed tomography (CT), and helium-3 (He-3) magnetic resonance
      imaging (MRI) with histopathology. Multiple MRI techniques were tested to obtain
      complementing physiologic information. Thirteen rabbits received SBRT to the
      right lower lobe of the lung. Specifically, 4 received 3 * 11 Gray (Gy), 6
      received 3 * 11 Gy and 50 mg/kg of amifostine pre-SRBT, and 3 received 3 * 7, 3 *
      9, or 3 * 13 Gy. Imaging was performed at baseline and 4, 8, 12, and 16 weeks
      post-SBRT. Ce-MRA perfusion difference between lungs in the irradiated group at
      16 weeks post-treatment was statistically significant (P = .04) whereas the
      difference in the irradiated + amifostine group was not (P = .30). Histologically
      observed low red blood cell (RBC) count and CT hypodensity suggests changes were
      primarily related to perfusion; however, structural changes, such as increased
      alveolar size, were also present. No changes in He-3 MRI lung ventilation were
      observed in either group. Although radiation-induced injury detected in rabbits
      as CT hypodensity contrasted with increased density observed in humans/rodents,
      the changes in ce-MRA and CT were still significantly reduced after the addition
      of amifostine to SBRT. Use of CT and selected MRI techniques helped to pinpoint
      primary physiologic changes.

PMID- 24926530
TI  - Effect of brachytherapy on NF-kappaB and VEGF in gastric carcinoma xenografts.
AB  - Iodine-125 (125I) seed irradiation can be used as an important supplementary
      treatment for unresectable advanced gastric cancer. However, the radiobiological
      mechanism underlying brachytherapy remains unclear. Therefore, we investigated
      the influence of continuous and low-energy 125I irradiation on the cell cycle
      distribution, apoptosis, expression of NF-kappaB and VEGF and tumor growth in a
      human gastric cancer xenograft model. To create an animal model of gastric
      cancer, SGC-7901 cells were surgically implanted into mice. The 60 mice bearing
      SGC-7901 gastric cancer xenografts were randomly separated into 2 groups. Sham
      seeds (0 mCi) were implanted into the control group (n=30); 125I seeds (0.6 mCi)
      were implanted into the treatment group (n=30). At 28 days after irradiation,
      apoptosis was detected by flow cytometry. fluorescence micrograph detected
      intense VEGF and NF-kappaB immunofluorescence in the tumor samples, and changes
      in NF-kappaB and VEGF mRNA and protein expression were assessed by real-time PCR
      and western blot analysis, respectively. The tumor volume and weight were
      measured 0-28 days after 125I seed implantation. 125I seed irradiation induced
      significant apoptosis and G2/M phase arrest. Reduction in the intensities of VEGF
      and NF-kappaB immunofluorescence in tumor vessels was observed after treatment.
      NF-kappaB and VEGF mRNA and protein expression levels were substantially lower in
      the implantation treatment group than in the control group. Consequently, 125I
      seed implantation inhibited cancer growth and reduced cancer volume. The present
      study revealed that 125I seed irradiation significantly induced apoptosis and
      cell cycle arrest in the human gastric cancer xenografts. 125I-induced changes in
      NF-kappaB and VEGF expression are suggested as potential mechanisms underlying
      effective brachytherapy.

PMID- 24926532
TI  - Enzyme-responsive hydrogel microparticles for pulmonary drug delivery.
AB  - Poly(ethylene glycol) based hydrogel microparticles were developed for pulmonary
      drug delivery. Hydrogels are particularly attractive for pulmonary delivery
      because they can be size engineered for delivery into the bronchi, yet also swell
      upon reaching their destination to avoid uptake and clearance by alveolar
      macrophages. To develop enzyme-responsive hydrogel microparticles for pulmonary
      delivery a new synthesis method based on a solution polymerization was developed.
      This method produces spherical poly(ethylene glycol) (PEG) microparticles from
      high molecular weight poly(ethylene glycol) diacrylate (PEGDA)-based precursors
      that incorporate peptides in the polymer chain. Specifically, we have synthesized
      hydrogel microparticles that degrade in response to matrix metalloproteinases
      that are overexpressed in pulmonary diseases. Small hydrogel microparticles with
      sizes suitable for lung delivery by inhalation were obtained from solid
      precursors when PEGDA was dissolved in water at a high concentration. The average
      diameter of the particles was between 2.8 and 4 MUm, depending on the molecular
      weight of the precursor polymer used and its concentration in water. The relation
      between the physical properties of the particles and their enzymatic degradation
      is also reported, where an increased mesh size corresponds to increased
      degradation. 

PMID- 24926531
TI  - The DCDC2/intron 2 deletion and white matter disorganization: focus on
      developmental dyslexia.
AB  - INTRODUCTION: The DCDC2 gene is involved in neuronal migration. Heterotopias have
      been found within the white matter of DCDC2-knockdown rats. A deletion in
      DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named 'regulatory
      element associated with dyslexia 1' (READ1), increases the risk for dyslexia. We
      hypothesized that DCDC2d can be associated to alterations of the white matter
      structure in general and in dyslexic brains. METHODS: Based on a full-factorial
      analysis of covariance (ANCOVA) model, we investigated voxel-based diffusion
      tensor imaging (VB-DTI) data of four groups of subjects: dyslexia with/without
      DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects
      upon correlation patterns between fractional anisotropy (FA) and reading scores.
      RESULTS: We found that FA was reduced in the left arcuate fasciculus and splenium
      of the corpus callosum in subjects with versus without DCDC2d, irrespective of
      dyslexia. Subjects with dyslexia and DCDC2d showed reduced FA, mainly in the left
      hemisphere and in the corpus callosum; their counterpart without DCDC2d showed
      similar FA alterations. Noteworthy, a conjunction analysis in impaired readers
      revealed common regions with lower FA mainly in the left hemisphere. When we
      compared subjects with dyslexia with versus without DCDC2d, we found lower FA in
      the inferior longitudinal fasciculus and genu of the corpus callosum,
      bilaterally. Normal readers with versus without DCDC2d had FA increases and
      decreases in both the right and left hemisphere. DISCUSSION: The major
      contribution of our study was to provide evidence relating genes, brain and
      behaviour. Overall, our findings support the hypothesis that DCDC2d is associated
      with altered FA. In normal readers, DCDC2-related anatomical patterns may mark
      some developmental cognitive vulnerability to learning disabilities. In subjects
      with dyslexia, DCDC2d accounted for both common - mainly located in the left
      hemisphere - and unique - a more severe and extended pattern - alterations of
      white matter fibre tracts.

PMID- 24926533
TI  - Metabolites and metals in Metazoa--what role do phytochelatins play in animals?
AB  - Phytochelatins are sulfur-rich metal-binding peptides, and phytochelatin
      synthesis is one of the key mechanisms by which plants protect themselves against
      toxic soft metal ions such as cadmium. It has been known for a while now that
      some invertebrates also possess functional phytochelatin synthase (PCS) enzymes,
      and that at least one species, the nematode Caenorhabditis elegans, produces
      phytochelatins to help detoxify cadmium, and probably also other metal and
      metalloid ions including arsenic, zinc, selenium, silver, and copper. Here, we
      review recent studies on the occurrence, utilization, and regulation of
      phytochelatin synthesis in invertebrates. The phytochelatin synthase gene has a
      wide phylogenetic distribution, and can be found in species that cover almost all
      of the animal tree of life. The evidence to date, though, suggests that the
      occurrence is patchy, and even though some members of particular taxonomic groups
      may contain PCS genes, there are also many species without these genes. For
      animal species that do possess PCS genes, some of them (e.g. earthworms) do
      synthesize phytochelatins in response to potentially toxic elements, whereas
      others (e.g. Schistosoma mansoni, a parasitic helminth) do not appear to do so.
      Just how (and if) phytochelatins in invertebrates complement the function of
      metallothioneins remains to be elucidated, and the temporal, spatial, and metal
      specificity of the two systems is still unknown. 

PMID- 24926534
TI  - High-performance aminated poly(phenylene sulfide)/ZnO nanocomposites for medical
      applications.
AB  - An aminated poly(phenylene sulfide) derivative (PPS-NH2) has been melt-blended
      with different contents of ZnO nanoparticles, and the morphology, thermal,
      mechanical, tribological, antibacterial, and dielectric properties of the
      resulting nanocomposites have been investigated. The nanoparticles were dispersed
      within the matrix without the need for surfactants or coupling agents. A gradual
      rise in the crystallization temperature and the degree of crystallinity was found
      with increasing ZnO loading, confirming that the nanoparticles act as nucleating
      agents for PPS-NH2 crystallization. The nanoparticles reduced the water
      absorption and strongly increased the thermal stability of the matrix, leading to
      an extraordinary increase in the initial degradation temperature of 80  degrees C
      at 8.0 wt % nanoparticle content. The results showed that the stiffness,
      strength, toughness, glass transition, and heat distortion temperature were
      remarkably enhanced, whereas the coefficient of thermal expansion decreased upon
      addition of ZnO, ascribed to strong hydrogen bonding interactions between the
      amino groups of the matrix and the hydroxyl moieties of the nanoparticles.
      Moreover, the nanocomposites retained the tensile properties after being exposed
      to several cycles of steam sterilization. More importantly, an unprecedented drop
      in wear rate of nearly 100-fold was attained in the nanocomposite with the
      highest loading, demonstrating the suitability of these nanoparticles for
      providing wear resistance to the matrix. All the nanocomposites displayed low
      dielectric constant and dielectric loss, hence can be employed as insulating
      materials in electrosurgical applications. They also exhibited active inhibition
      against both Gram-positive and Gram-negative bacteria, which was gradually
      enhanced with increasing ZnO content. These nanocomposites are suitable as
      lightweight high-performance materials in the field of medicine and dentistry. 

PMID- 24926535
TI  - Selective functionalization and loading of biomolecules in crystalline silicon
      nanotube field-effect-transistors.
AB  - Crystalline silicon nanotubes (Si NTs) provide distinctive advantages as
      electrical and biochemical analysis scaffolds through their unique morphology and
      electrical tunability compared to solid nanowires or amorphous/non-conductive
      nanotubes. Such potential is investigated in this report. Gate-dependent four
      probe current-voltage analysis reveals electrical properties such as resistivity
      to differ by nearly 3 orders of magnitude between crystalline and amorphous Si
      NTs. Analysis of transistor transfer characteristics yields a field effect
      mobility of 40.0 cm(2) V(-1) s(-1) in crystalline Si NTs. The hollow morphology
      also allows selective inner/outer surface functionalization and loading
      capability either as a carrier for molecular targets or as a nanofluidic channel
      for biomolecular assays. We present for the first time a demonstration of
      internalization of fluorescent dyes (rhodamine) and biomolecules (BSA) in Si NTs
      as long as 22 MUm in length. 

PMID- 24926536
TI  - Abdominal obesity modifies long-term associations between periodontitis and
      markers of systemic inflammation.
AB  - OBJECTIVE: Periodontitis is considered to promote atherosclerosis and
      cardiovascular diseases through increased low-grade systemic inflammation.
      However, there is no information on the long-term impact of periodontitis on
      systemic inflammation from cohort studies. Thus, this study aims to assess the
      impact of periodontitis on systemic inflammation (fibrinogen and white blood
      cells (WBC)) in a population-based longitudinal survey in north-eastern Germany.
      METHODS: The study sample comprised 2622 subjects from the Study of Health in
      Pomerania with complete 5- and 11-year follow-ups. Periodontitis was assessed by
      probing depth and clinical attachment level. Multilevel regression analyses were
      applied to evaluate associations between periodontitis measures and i)
      fibrinogen/WBC count using 11-year follow-up data and ii) respective z-scores of
      fibrinogen/WBC count using 5- and 11-year follow-up data. We adjusted for common
      cardiovascular risk factors and stratified analyses by abdominal obesity (P for
      interaction <0.10). RESULTS: In lean subjects, beta-coefficients of mean probing
      depth were B = 0.13 (0.08-0.019; P < 0.001) for fibrinogen and B = 0.50 (0.37
      0.64; P < 0.001) for WBC count using 11-year follow-up data only. For lean
      subjects, models using z-scores confirmed that increased mean probing depths were
      associated with increased fibrinogen z-scores (B = 0.14 (0.09-0.18; P < 0.001))
      and increased WBC z-scores (B = 0.16 (0.11-0.20; P < 0.001)). Consistent results
      were found for mean clinical attachment levels. For abdominally obese subjects,
      relations between periodontitis measures and levels of inflammation markers were
      less pronounced or non-significant. CONCLUSION: Modified by abdominal obesity,
      periodontitis affected systemic inflammation in a significant dose-dependent
      manner. Results contribute to the discussion on how periodontitis is linked to
      atherosclerosis and cardiovascular diseases.

PMID- 24926537
TI  - A new piece in the puzzling effect of n-3 fatty acids on atherosclerosis?
AB  - Omega-3 fatty acids (n-3) FA are reported to be protective against cardiovascular
      disease (CVD), notably through their beneficial action on atherosclerosis
      development. In this context dietary intake of long-chain marine eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) is recommended and randomised trials
      largely support that EPA and DHA intake is associated with a reduction of CVD.
      However, mechanisms governing the atheroprotective action of n-3 FA are still
      unclear and numerous studies using mouse models conducted so far do not allow to
      reach a precise view of the cellular and molecular effects of n-3 FA on
      atherosclerosis. In the current issue of Atherosclerosis, Chang et al. provide
      important new information on the anti-atherogenic properties of n-3 FA by
      analysing the incremental replacement of saturated FA by pure fish oil as a
      source of EPA and DHA in Ldlr(-/-) mice fed a high fat/high cholesterol diet. 

PMID- 24926538
TI  - Antifungal amphidinol 18 and its 7-sulfate derivative from the marine
      dinoflagellate Amphidinium carterae.
AB  - Two new polyketides of the amphidinol family, amphidinol 18 (AM18, 1) and its
      corresponding 7-sulfate derivative (AM19, 2), have been isolated from the MeOH
      extract of the dinoflagellate Amphidinium carterae. Structure elucidation of the
      two polyoxygenated molecules has been accomplished by extensive use of
      spectroscopic and spectrometric techniques. AM18 exhibited antifungal activity
      against Candida albicans at 9 MUg/mL. 

PMID- 24926540
TI  - Lung cancer screening using low-dose computed tomography--keeping participants
      out of Harm's way.

PMID- 24926541
TI  - Cigarette smoking and systemic therapy for lung cancer: considering the evidence
      to improve cancer care.

PMID- 24926542
TI  - Effects of cigarette smoking on metabolism and effectiveness of systemic therapy
      for lung cancer.
AB  - INTRODUCTION: Cigarette smoke associated polycyclic aromatic hydrocarbons can
      induce key drug-metabolizing enzymes of cytochrome P450 and isoforms of the
      glucuronyl transferases families. These enzymes metabolize several systemic
      therapies for lung cancer. Induction of these enzymes may lead to accelerated
      clearance with resultant impact on systemic therapy efficacy and toxicity in
      smokers compared with nonsmokers. This article reviews published literature
      regarding the influence of smoking as it relates to alteration of metabolism of
      systemic therapy in lung cancer. METHODS: A structured search of the National
      Library of Medicine's PubMed/MEDLINE identified relevant articles. Data were
      abstracted and analyzed to summarize the findings. RESULTS: Studies that analyzed
      pharmacokinetic data were prospective. Smokers receiving erlotinib exhibited
      rapid clearance, requiring a higher dose to reach equivalent systemic exposure
      compared with nonsmokers. Smokers receiving irinotecan also demonstrated
      increased clearance and lower systemic exposure. There was no difference in
      clearance of paclitaxel or docetaxel in smokers. Chemotherapy-associated
      neutropenia was worse in nonsmokers compared with smokers in patients treated
      with paclitaxel, docetaxel, irinotecan, and gemcitabine. CONCLUSIONS: Systemic
      therapy for lung cancer has a narrow therapeutic index such that small changes in
      plasma concentrations or exposure in smokers may result in suboptimal therapy and
      poor outcomes. Smoking cessation must be emphasized at each clinical visit.
      However, prospective trials should take into consideration the effects of smoking
      history on drug pharmacokinetics and efficacy. The metabolizing enzyme phenotype
      in smokers may require individualized dose algorithms for specific agents.

PMID- 24926543
TI  - Feasibility and potential utility of multicomponent exhaled breath analysis for
      predicting development of radiation pneumonitis after stereotactic ablative
      radiotherapy.
AB  - INTRODUCTION: In this prospective pilot study, we evaluated the feasibility and
      potential utility of measuring multiple exhaled gases as biomarkers of radiation
      pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR)
      for lung tumors. METHODS: Breath analysis was performed for 26 patients receiving
      SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon
      monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured
      before and immediately after each fraction using real-time, infrared laser
      spectroscopy. RP development (CTCAE grade >=2) was correlated with baseline gas
      concentrations, acute changes in gas concentrations after each SABR fraction, and
      dosimetric parameters. RESULTS: Exhaled breath analysis was successfully
      completed in 77% of patients. Five of 20 evaluable patients developed RP at a
      mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations,
      defined as percent changes between each pre-fraction and post-fraction
      measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and
      0.015, respectively). In an exploratory analysis, a combined predictor of
      baseline eNO greater than 24 parts per billion and acute decrease in eCO less
      than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor
      eCO2 concentrations were significantly associated with RP development. Although
      generally higher in patients destined to develop RP, dosimetric parameters were
      not significantly associated with RP development. CONCLUSIONS: The majority of
      SABR patients in this pilot study were able to complete exhaled breath analysis.
      Baseline concentrations and acute changes in concentrations of exhaled breath
      components were associated with RP development after SABR. If our findings are
      validated, exhaled breath analysis may become a useful approach for noninvasive
      identification of patients at highest risk for developing RP after SABR.

PMID- 24926544
TI  - Final efficacy and safety results of pemetrexed continuation maintenance therapy
      in the elderly from the PARAMOUNT phase III study.
AB  - INTRODUCTION: The PARAMOUNT Phase III trial showed that maintenance pemetrexed
      after pemetrexed plus cisplatin induction was well tolerated and effective for
      patients with advanced nonsquamous non-small-cell lung cancer. Approximately 17%
      of patients receiving maintenance therapy in this study were 70 years of age or
      older. Here we report efficacy and safety results from the PARAMOUNT study for
      elderly (>=70 years) and non-elderly (<70 years) patients. METHODS: Final
      efficacy and safety data from the PARAMOUNT study were analyzed post hoc using
      subgroup analyses for elderly and non-elderly patients. RESULTS: The median age
      was 73 years in the elderly subgroup (n = 92) and 60 years in the non-elderly
      subgroup (n = 447). Subgroups had similar baseline characteristics, except for a
      higher percentage of males and patients with a performance status of one in the
      elderly subgroup. For elderly patients, the median PFS was 6.4 months for
      pemetrexed and 3.0 months for placebo; the median OS was 13.7 months for
      pemetrexed and 12.1 months for placebo. For non-elderly patients, the median PFS
      was 4.0 months for pemetrexed and 2.8 months for placebo; the median OS was 13.9
      months for pemetrexed and 10.8 months for placebo. Elderly patients experienced
      similar levels of low-grade toxicities, but had a higher percentage of grade 3/4
      anemia and neutropenia than non-elderly patients, although importantly, this did
      not translate into increased febrile neutropenia. CONCLUSIONS: Continuation
      maintenance pemetrexed had comparable survival and toxicity profiles in the
      elderly and non-elderly subgroups. However, grade 3/4 anemia and neutropenia were
      numerically higher for elderly patients.

PMID- 24926546
TI  - Prognostic factors for cure, recurrence and long-term survival after surgical
      resection of thymoma.
AB  - INTRODUCTION: To determine long-term outcome and risk factors for recurrence
      after thymectomy. METHODS: Patients who underwent thymectomy (n = 262) for a
      thymic tumor (1986-2010) were identified from a prospective database. Patients
      were classified according to World Helath Organization (WHO) histologic
      classification, Masaoka staging system, and completeness of resection. Risk
      factors for recurrence: WHO histology, tumor size, Masaoka stage and completeness
      of resection were analyzed. RESULTS: Of 262 patients, 51% were female, median age
      was 55 years, and 39% had myasthenia gravis. Median follow-up was 7.5 years,
      median tumor size was 5.4 cm, and Masaoka stage distribution was: I (25%), II
      (47%), III (17%), IV (4%), and (7%) not classified. Of 200 patients classified
      under the WHO system, there were (7%) type A, (22%) type AB, and (71%) type B;
      83% had complete resection. One-hundred and sixty-nine patients received adjuvant
      radiotherapy, eight adjuvant chemoradiotherapy and 14 neoadjuvant
      chemoradiotherapy. Overall survival was 95% at 5 years, 91% at 10 years and 91%
      at 15 years. Recurrence occurred in 12 patients and disease-related death in four
      patients. Five patients underwent re-resection for recurrence with survival of 2
      15 years. Only Masaoka stage and tumor size were associated with statistically
      significant risk of recurrence on multivariate analysis. CONCLUSION: Resectable
      thymoma is associated with excellent prognosis. Aggressive resection of recurrent
      disease yielded excellent long-term results. Higher Masaoka stage is associated
      with a greater chance of incomplete resection. Higher Masaoka stage and
      increasing tumor size are independent factors associated with recurrence.

PMID- 24926545
TI  - Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote
      malignant pleural mesothelioma.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is a deadly disease with poor
      prognosis and few treatment options. We characterized and elucidated the roles of
      C-MYC and PVT1 involved in the pathogenesis of MPM. METHODS: We used small
      interfering RNA (siRNA)-mediated knockdown in MPM cell lines to determine the
      effect of C-MYC and PVT1 abrogation on MPM cells undergoing apoptosis,
      proliferation, and cisplatin sensitivity. We also characterized the expression of
      microRNAs spanning the PVT1 region in MPM cell lines. Copy number analysis was
      measured by quantitative polymerase chain reaction and fluorescence in situ
      hybridization. RESULTS: Copy number analysis revealed copy number gains (CNGs) in
      chromosomal region 8q24 in six of 12 MPM cell lines. MicroRNA analysis showed
      high miR-1204 expression in MSTO-211H cell lines with four copies or more of
      PVT1. Knockdown by siRNA showed increased PARP-C levels in MSTO-211H transfected
      with siPVT1 but not in cells transfected with siC-MYC. C-MYC and PVT1 knockdown
      reduced cell proliferation and increased sensitivity to cisplatin. Analysis of
      the expression of apoptosis-related genes in the MSTO-211H cell line suggested
      that C-MYC maintains a balance between proapoptotic and antiapoptotic gene
      expression, whereas PVT1 and, to a lesser extent, miR-1204 up-regulate
      proapoptotic genes and down-regulate antiapoptotic genes. Fluorescence in situ
      hybridization analysis of MPM tumor specimens showed a high frequency of both
      CNGs (11 of 75) and trisomy (three copies; 11 of 75) for the C-MYC locus.
      CONCLUSION: Our results suggest that C-MYC and PVT1 CNG promotes a malignant
      phenotype of MPM, with C-MYC CNG stimulating cell proliferation and PVT1 both
      stimulating proliferation and inhibiting apoptosis.

PMID- 24926547
TI  - Preoperative computed tomography findings predict surgical resectability of
      thymoma.
AB  - INTRODUCTION: The aim of the study was to identify preoperative computed
      tomography (CT) imaging characteristics that correlated with surgical
      resectability. METHODS: We retrospectively reviewed the CT scans of 133 patients
      who underwent surgical resection for thymoma at our institution between July 21,
      1997, and September 22, 2010. Imaging characteristics recorded included tumor
      size, attenuation, contact of mediastinal vessels, tumor morphology, infiltration
      of surrounding fat, changes in the adjacent lung parenchyma, lymphadenopathy, and
      pleural involvement. RESULTS: The study group included 66 men and 67 women, aged
      23-88 years (mean 58.8 years). Eighty patients (60.2%) were Masaoka stage I or II
      and 53 (39.8%) were Masaoka stage III or IV. Twenty-three patients (17.3%) had an
      incomplete surgical resection. Of these, 15 patients had microscopic residual
      disease (11.2%) and eight had gross residual disease (6.0%). The preoperative CT
      characteristics that correlated with an incomplete surgical resection included a
      lobulated tumor contour (p = 0.016), greater than or equal 50% abutment of the
      circumference of an adjacent vessel (p < 0.001), thoracic lymphadenopathy (p =
      0.029), adjacent lung changes (p = 0.005) and pleural nodularity (p = 0.001).
      Tumor size was larger in the incompletely versus completely resected groups, with
      mean values of 9.7 and 6.9 cm (p value 0.013). On multivariate analysis, only
      degree of abutment of adjacent vessels and pleural nodularity were independent
      predictors of incomplete resection. CONCLUSIONS: Preoperative CT findings can
      predict the likelihood of successful surgical resection and could help to
      identify patients who might benefit from neoadjuvant chemotherapy.

PMID- 24926548
TI  - A randomized, phase 2 trial of Docetaxel with or without PX-866, an irreversible
      oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or
      metastatic non-small-cell lung cancer.
AB  - INTRODUCTION: The phosphotidylinositol-3 kinase/serine-threonine kinase
      (AKT)/mammalian target of rapamycin signaling pathway is frequently altered in
      non-small-cell lung cancer (NSCLC). PX-866 is an oral, irreversible, pan-isoform
      inhibitor of phosphotidylinositol-3 kinase. Preclinical models revealed synergy
      with docetaxel and a phase 1 trial demonstrated tolerability of this combination.
      This randomized phase 2 study evaluated PX-866 combined with docetaxel in
      patients with advanced, refractory NSCLC. METHODS: Patients with locally
      advanced, recurrent, or metastatic NSCLC who had received at least one and no
      more than two prior systemic treatment regimens were randomized (1:1) to a
      combination of docetaxel (75 mg/m intravenous every 21 days) with or without PX
      866 (8 mg orally daily; arms A and B, respectively). The primary end point was
      progression-free survival (PFS). Secondary end points included objective response
      rate, overall survival (OS), toxicity, and correlation of biomarker analyses with
      efficacy outcomes. RESULTS: A total of 95 patients were enrolled. Median PFS was
      2 months in arm A and 2.9 months in arm B (p = 0.65). Objective response rates
      were 6% and 0% in arms A and B, respectively (p = 0.4). There was no difference
      in OS between the two arms (7.0 versus 9.2 months; p = 0.9). Grade 3 or higher
      adverse events were infrequent, but more common in the combination arm with
      respect to diarrhea (7% versus 2%), nausea (4% versus 0%), and vomiting (7%
      versus 0%). PIK3CA mutations or PTEN loss were infrequently observed. CONCLUSION:
      The addition of PX-866 to docetaxel did not improve PFS, response rate, or OS in
      patients with advanced, refractory NSCLC without molecular preselection.

PMID- 24926549
TI  - B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid
      histology and poor prognosis.
AB  - INTRODUCTION: B7 homolog 1 (B7-H1; aka programmed cell death 1 ligand 1) is a
      negative costimulatory molecule that is associated with poor prognosis in many
      tumor types. Given the poor prognosis and the limited treatments available for
      mesothelioma, we decided to examine B7-H1 expression and its association with
      survival in patients with mesothelioma. METHODS: Expression of B7-H1 was
      determined in 106 patients using a mouse monoclonal antihuman B7-H1 (clone 5H1
      A3) antibody with immunohistochemistry. Positive expression was defined as >=5%
      positively stained cells. Clinicopathologic features and survival were compared
      between B7-H1-positive and B7-H1-negative groups. RESULTS: Malignant
      mesotheliomas of 42 patients (40%) expressed B7-H1. Patients with B7-H1-postive
      tumors were less likely to be offered or undergo therapeutic surgery (p = 0.03).
      All sarcomatoid mesotheliomas except one desmoplastic subtype expressed B7-H1.
      Survival was significantly decreased for patients whose tumors expressed B7-H1 (5
      months median, 2-9.5 months interquartile range) compared with those whose tumors
      did not (14.5 months, 9.25-19 months; p < 0.0001). In a multivariate model, B7-H1
      expression and sarcomatoid mesothelioma remained significantly associated with
      worse survival (risk ratio 1.71, 95% confidence interval 1.03-2.78 [p = 0.04] and
      risk ratio 2.18, 1.08-4.23 [p = 0.03], respectively). CONCLUSIONS: B7-H1 is
      expressed in a substantial proportion of malignant pleural mesotheliomas and is
      associated with poor survival. Almost all malignant pleural mesotheliomas with
      sarcomatoid differentiation expressed B7-H1. The expression of B7-H1 may have
      important therapeutic implications for the management of malignant pleural
      mesothelioma.

PMID- 24926550
TI  - 9q33.3, a stress-related chromosome region, contributes to reducing lung squamous
      cell carcinoma risk.
AB  - BACKGROUND: Human chromosome 9q33.3 is one of the most important loci for
      pathophysiological stresses with complex genetic traits. We hypothesized that the
      common single-nucleotide polymorphisms on this region may affect non-small-cell
      lung cancer risk. METHODS: We genotyped 43 single-nucleotide polymorphisms that
      span 13 genes on 9q33.3 in two independent cohorts: the discovery study including
      485 cases and 532 controls (North China) and the replicative study including 1063
      cases and 1247 controls (South China). Both of the discovery cohort and the
      replicative cohort were included in the combined study. RESULTS: In the discovery
      study, we identified a potential protective locus rs10118570 in mitogen-activated
      protein kinase associated protein 1 with a lower population attributable risk
      under logistical regression adjusted by age, gender, smoking, and drinking status
      (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI] 0.10-0.71, p = 1.138
      * 10 for genotype GG in lung squamous cell carcinoma). This protective quality
      increased in a dose-dependent manner as genotype GG decreased (ptrend = 9.675 *
      10). Replicative and combined studies showed consistent association for this
      genotype (replicative: adjusted OR 0.36, 95% CI 0.20-0.66, p = 6.109 * 10, ptrend
      = 7.386 * 10; combined: adjusted OR 0.33, 95% CI 0.18-0.55, p = 1.259 * 10,
      ptrend = 7.725 * 10). CONCLUSION: We concluded that mitogen-activated protein
      kinase associated protein 1 rs10118570 may be an important protective factor for
      developing better management strategies in lung squamous cell carcinoma.

PMID- 24926551
TI  - Multiplexed molecular profiling of lung cancer using pleural effusion.
AB  - INTRODUCTION: Pleural effusion is frequently observed in patients with advanced
      lung cancer. Although effusion can be obtained less invasively and repeatedly,
      its use in multiplexed molecular profiling has not been fully investigated.
      METHODS: Between July 2011 and April 2013, pleural effusion samples were obtained
      from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for
      EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET,
      FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes
      using pyrosequensing and/or capillary electrophoresis, quantitative reverse
      transcriptase polymerase chain reaction, and reverse-transcriptase polymerase
      chain reaction, respectively. RESULTS: One hundred and two samples from 84
      patients were analyzed. Adenocarcinoma was the most common histological subtype
      (82%). Genetic abnormalities were detected in 42% of patients. The most common
      abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%),
      KRAS mutation, and EGFR amplification (4%, each). Concordance rates between
      pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%.
      Among 11 patients who provided samples at multiple time points, changes in
      molecular profile over the course of treatment were observed in five patients.
      CONCLUSIONS: The use of pleural effusion for multiplexed molecular testing and
      real-time monitoring in lung cancer was demonstrated.

PMID- 24926552
TI  - Multiple pulmonary chondroid hamartoma.

PMID- 24926553
TI  - Detection of EGFR mutations in the plasma of patients with lung adenocarcinoma
      for real-time monitoring of therapeutic response to tyrosine kinase inhibitors?

PMID- 24926554
TI  - A severe photosensitivity dermatitis caused by crizotinib.

PMID- 24926555
TI  - Palliative radiotherapy for malignant airway obstruction requiring mechanical
      ventilation: answer or anguish?

PMID- 24926556
TI  - Future directions in palliative radiotherapy for malignant airway obstruction
      requiring mechanical ventilation.

PMID- 24926557
TI  - Coexistence of tyrosine kinase inhibitor-sensitizing and resistant EGFR mutations
      in an untreated lung adenocarcinoma patient and response to erlotinib.

PMID- 24926558
TI  - To the editor.

PMID- 24926559
TI  - In response.

PMID- 24926560
TI  - Curcumin increases gelatinase activity in human neutrophils by a p38 mitogen
      activated protein kinase (MAPK)-independent mechanism.
AB  - Curcumin has been found to possess anti-inflammatory activities and neutrophils,
      key players in inflammation, were previously found to be important targets to
      curcumin in a few studies. For example, curcumin was found to induce apoptosis in
      neutrophils by a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism.
      However, the role of curcumin on the biology of neutrophils is still poorly
      defined. To study the role of curcumin on neutrophil degranulation and to
      determine the role of p38 MAPK, human neutrophils were freshly isolated from
      healthy individuals and incubated in vitro with curcumin. Degranulation was
      studied at three levels: surface expression of granule markers by flow cytometry;
      release of matrix metallopeptidase-9 (MMP-9 or gelatinase B) enzyme into
      supernatants by Western blot; and gelatinase B activity by zymography. Activation
      of p38 MAPK was studied by monitoring its tyrosine phosphorylation levels by
      western blot and its role by the utilization of a pharmacological inhibitor. The
      results indicate that curcumin increased the cell surface expression of CD35
      (secretory vesicle), CD63 (azurophilic granules), and CD66b (gelatinase granules)
      in neutrophils. Also, curcumin increased the release and enzymatic activity of
      gelatinase B in the extracellular milieu and activated p38 MAP kinase in these
      cells. However, in contrast to fMLP, curcumin-induced enzymatic activity and
      secretion of gelatinase B were not reversed by use of a p38 inhibitor. Finally,
      it was found that curcumin was able to enhance phagocytosis. Taken together, the
      results here demonstrate that curcumin induced degranulation in human neutrophils
      and that the increased gelatinase activity is not dependent on p38 MAPK
      activation. Therefore, degranulation is another human neutrophil function that
      could be modulated by curcumin, as well as phagocytosis.

PMID- 24926561
TI  - Water is a key factor to alter the structure and electrochemical properties of
      carboxylate-bridged dimanganese(II) complexes.
AB  - The synthesis and physical properties of dimanganese(II) compounds with varying
      numbers of water ligands housed in the four bulky carboxylate motifs, including
      the first complex with a parallelogram core {Mn2(MU-OH2)2(MU-O2CR)}(3+) unit, are
      described. The isolation of these complexes revealed how water could alter the
      structural and electrochemical properties of similar carboxylate-bridged
      dimanganese(II) cores that may occur in a variety of active sites of Mn
      containing metalloenzymes. These studies support the notion that water molecules
      in coordination spheres of active sites of metalloproteins are not a simple
      spectator medium but the modulation factor of structures and functions.

PMID- 24926562
TI  - n->pi* interactions engender chirality in carbonyl groups.
AB  - An n->pi* interaction stems from the delocalization of the electron pair (n) of a
      donor group into the antibonding orbital (pi*) of a carbonyl group.
      Crystallographic analyses of five pairs of diastereoisomers demonstrate that an n
      >pi* interaction can induce chirality in an otherwise planar, prochiral carbonyl
      group. Thus, a subtle delocalization of electrons can have stereochemical
      consequences. 

PMID- 24926563
TI  - Combined effects of asbestos and cigarette smoke on the development of lung
      adenocarcinoma: different carcinogens may cause different genomic changes.
AB  - The carcinogens in cigarette smoke are distinct from asbestos. However, an
      understanding of their differential effects on lung adenocarcinoma development
      remains elusive. We investigated loss of heterozygosity (LOH) and the p53
      mutation in 132 lung adenocarcinomas, for which asbestos body burden (AB; in
      numbers per gram of dry lung) was measured using adjacent normal lung. All cases
      were classified into 9 groups based on a matrix of cumulative smoking (CS in pack
      years; CS=0, 0<CS<25, >=25 CS) and AB (AB=0, 0<AB<1,000, >=1,000 AB). AB=0
      indicates a lower level than the detection limit of ~100. LOH frequency increased
      only slightly with the elevation of CS in the AB=0 groups. In the AB>0 groups,
      LOH frequency increased as AB and/or CS was elevated and was significantly higher
      in the >=1,000 AB, >=25 CS group (p=0.032). p53 mutation frequency was the lowest
      in the AB=0, CS=0 group, increased as AB and/or CS rose, and was significantly
      higher in the >=1,000 AB, >=25 CS group (p=0.039). p53 mutations characteristic
      of smoking were frequently observed in the CS>0 groups contrary to non-specific
      mutations in the CS=0, AB>0 groups. Combined effects of asbestos and smoking were
      suggested by LOH and p53 analyses. Sole exposure to asbestos did not increase LOH
      frequency but increased non-specific p53 mutations. These findings indicate that
      the major carcinogenic mechanism of asbestos may be tumor promotion, acting in an
      additive or synergistic manner, contributing to the genotoxic effect of smoking.
      Since this study was based on a general cancer center's experience, the limited
      sample size did not permit the consideration that the result was conclusive.
      Further investigation with a large sample size is needed to establish the
      mechanism of asbestos-induced lung carcinogenesis.

PMID- 24926565
TI  - A novel flavin derivative reveals the impact of glucose on oxidative stress in
      adipocytes.
AB  - We present the synthesis and characterisation of naphthalimide-flavin redox
      sensor 1 (NpFR1), a novel flavin molecule that is almost non-fluorescent in
      reduced form, but oxidation gives rise to a 125-fold increase in fluorescence.
      Confocal microscopy experiments confirm that is sensitive to redox changes within
      living cells.

PMID- 24926564
TI  - Proteomic quantification and site-mapping of S-nitrosylated proteins using
      isobaric iodoTMT reagents.
AB  - S-Nitrosylation is a redox-based protein post-translational modification in
      response to nitric oxide signaling and is involved in a wide range of biological
      processes. Detection and quantification of protein S-nitrosylation have been
      challenging tasks due to instability and low abundance of the modification. Many
      studies have used mass spectrometry (MS)-based methods with different thiol
      reactive reagents to label and identify proteins with S-nitrosylated cysteine
      (SNO-Cys). In this study, we developed a novel iodoTMT switch assay (ISA) using
      an isobaric set of thiol-reactive iodoTMTsixplex reagents to specifically detect
      and quantify protein S-nitrosylation. Irreversible labeling of SNO-Cys with the
      iodoTMTsixplex reagents enables immune-affinity detection of S-nitrosylated
      proteins, enrichment of iodoTMT-labeled peptides by anti-TMT resin, and
      importantly, unambiguous modification site-mapping and multiplex quantification
      by liquid chromatography-tandem MS. Additionally, we significantly improved anti
      TMT peptide enrichment efficiency by competitive elution. Using ISA, we
      identified a set of SNO-Cys sites responding to lipopolysaccharide (LPS)
      stimulation in murine BV-2 microglial cells and revealed effects of S-allyl
      cysteine from garlic on LPS-induced protein S-nitrosylation in antioxidative
      signaling and mitochondrial metabolic pathways. ISA proved to be an effective
      proteomic approach for quantitative analysis of S-nitrosylation in complex
      samples and will facilitate the elucidation of molecular mechanisms of
      nitrosative stress in disease. 

PMID- 24926566
TI  - Influence of olive leaf processing on the bioaccessibility of bioactive
      polyphenols.
AB  - Olive leaves are rich in bioactive compounds, which are beneficial for humans.
      The objective of this work was to assess the influence of processing conditions
      (drying and extraction) of olive leaves on the extract's bioaccessibility. Thus,
      extracts obtained from dried olive leaves (hot air drying at 70 and 120  degrees
      C or freeze-drying) by means of conventional or ultrasound-assisted extraction
      were subjected to in vitro digestion. Antioxidant capacity, total phenolic
      content, and HPLC-DAD/MS/MS analysis were carried out during digestion. The
      dehydration treatment used for the olive leaves did not have a meaningful
      influence on bioaccessibility. The digestion process significantly (p<0.05)
      affected the composition of the extracts. Oleuropein and verbascoside were quite
      resistant to gastric digestion but were largely degraded in the intestinal phase.
      Nevertheless, luteolin-7-O-glucoside was the most stable polyphenol during the in
      vitro simulation (43% bioaccessibility). Therefore, this compound may be taken
      into consideration in further studies that focus on the bioactivity of olive leaf
      extracts.

PMID- 24926567
TI  - Oxidation of purine nucleotides by Triplet 3,3',4,4'-benzophenone tetracarboxylic
      acid in aqueous solution: pH-dependence.
AB  - The photo-oxidation of purine nucleotides adenosine-5'-monophosphate (AMP) and
      guanosine-5'-monophosphate (GMP) by 3,3',4,4'-benzophenone tetracarboxylic acid
      (TCBP) has been investigated in aqueous solutions using nanosecond laser flash
      photolysis (LFP) and time-resolved chemically induced dynamic nuclear
      polarization (CIDNP). The pH dependences of quenching rate constants and of
      geminate polarization are measured within a wide range of pH values. As a result,
      the chemical reactivity of reacting species in different protonation states is
      determined. In acidic solution (pH < 4.9), the quenching rate constant is close
      to the diffusion-controlled limit: kq = 1.3 * 10(9) M(-1) s(-1) (GMP), and kq =
      1.2 * 10(9) M(-1) s(-1) (AMP), whereas in neutral and basic solutions it is
      significantly lower: kq = 2.6 * 10(8) M(-1) s(-1) (GMP, 4.9 < pH < 9.4), kq = 3.5
      * 10(7) M(-1) s(-1) (GMP, pH > 9.4), kq = 1.0 * 10(8) M(-1) s(-1) (AMP, pH >
      6.5). Surprisingly, the strong influence of the protonation state of the
      phosphoric group on the oxidation of adenosine-5'-monophosphate is revealed: the
      deprotonation of the AMP phosphoric group (6.5) decreases the quenching rate
      constant from 5.0 * 10(8) M(-1) s(-1) (4.9 < pH < 6.5) to 1.0 * 10(8) M(-1) s(-1)
      (pH > 6.5). 

PMID- 24926568
TI  - The effects of anxiety and exercise-induced fatigue on shooting accuracy and
      cognitive performance in infantry soldiers.
AB  - Operational performance in military settings involves physical and mental skills
      that are generally investigated separately in lab settings, leading to reduced
      ecological validity. Therefore, we investigated the effects of anxiety and
      exercise-induced fatigue, separately and in combination, on cognitive and
      shooting performance of 22 soldiers in a real-world setting. Findings indicated
      that soldiers' shooting accuracy and decision-making and mathematical skills
      decreased significantly under anxiety. Whether exercise-induced fatigue was
      beneficial or detrimental to task performance depended on the task at hand. The
      increased arousal levels through exercise prevented shooting accuracy from
      deteriorating in the decision task. In contrast, cognitive performance suffered
      from the increased arousal: participants more often failed to shoot when being
      fired at by an opponent and also math performance seemed to decrease. We conclude
      that anxiety can deteriorate soldier performance and that exercise-induced
      fatigue may improve or deteriorate performance in combination with anxiety
      depending on the nature of the task. PRACTITIONER SUMMARY: Soldiers encounter
      anxiety and exercise-induced fatigue. We investigated to what degree these
      factors influence soldiers' shooting and cognitive performance. Experimental
      manipulation of anxiety and exercise during a representative field course
      indicated decreased performance under anxiety. Exercise prevented shooting
      accuracy from deteriorating under anxiety, although cognitive performance was
      negatively affected after exercise.

PMID- 24926571
TI  - Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis
      progression in rats under unilateral ureteral obstruction.
AB  - The aim of the present study was to examine the protective effects of the urinary
      trypsin inhibitor ulinastatin (UTI) on renal interstitial inflammation and
      fibrosis in rats subjected to unilateral ureteral obstruction (UUO). A total of
      24 male Wistar rats were randomly divided into the three groups; the sham
      operation (SOR) group (n=8), the UUO group (n=8) and the UUO+UTI group (post-UUO
      UTI treatment, n=8). UUO was performed with complete ligation of the left ureter.
      As a medical intervention, saline (4 ml kg-1 d-1) and UTI (40000 units kg-1 d-1)
      were injected, respectively, into the animals of the corresponding groups on day
      one following surgery. The rats in all three groups were euthanized on day seven
      post surgery. Blood samples were harvested for blood urea nitrogen (BUN) and
      serum creatinine (Scr) content measurements. The degree of interstitial
      pathological changes in the tissues from the obstructed kidneys were observed
      through hematoxylin and eosin (H&E) and Masson staining. The CD68+ macrophage
      amount, tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta),
      nuclear factor-kappaB (NF-kappaB), transforming growth factor-beta1 (TGF-beta1)
      and type I collagen (Col-I) levels were examined immunohistochemically. The
      protein expression levels of NF-kappaB were examined using western blot analysis.
      Total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of
      homogenates were measured spectrophotometrically. The results revealed that
      ulinastatin had no statistically significant effect on the BUN and Scr levels
      (P>0.05). However, in comparison with the SOR group, the UUO group exhibited
      significantly more severe renal interstitial pathological injury in terms of
      tubular dilation, epithelial atrophy, renal interstitial inflammatory cell
      infiltration and proliferation of fibrous tissues, as well as significantly
      elevated levels of interstitial CD68+ macrophages, IL-1beta, TNF-alpha, NF
      kappaB, TGF-beta1 and Col-I (P<0.01). UTI treatment significantly reduced UUO
      induced renal interstitial damage with reduced levels of interstitial CD68+
      macrophages, IL-1beta, TNF-alpha, NF-kappaB, TGF-beta1 and Col-I and MDA
      (P<0.05), and increased SOD levels (P<0.05). In conclusion, the present study
      indicated that UTI is able to effectively inhibit UUO-side renal interstitial
      inflammatory reaction and fibrosis in UUO-inflicted rats.

PMID- 24926572
TI  - Efficient asymmetric synthesis of spiro-2(3H)-furanones via phase-transfer
      catalyzed alkynylation.
AB  - Efficient asymmetric synthesis of spiro-2(3H)-furanones was achieved via phase
      transfer-catalyzed highly enantioselective alkynylation of cyclic beta-keto
      esters with hypervalent iodine reagents. 

PMID- 24926574
TI  - Editorial.

PMID- 24926573
TI  - Nonsurgical periocular rejuvenation: advanced cosmetic uses of neuromodulators
      and fillers.
AB  - PURPOSE OF REVIEW: To review the current literature regarding aesthetic
      enhancement using facial neuromodulators and fillers and to present advanced
      techniques using facial injectables for periocular rejuvenation. RECENT FINDINGS:
      The authors provide a summary of traditional periocular locations for the
      injection of neuromodulators and dermal fillers. The authors also present novel
      and advanced techniques utilizing injectables in the periocular region. SUMMARY:
      Minimally invasive procedures with little-to-no recovery time are continuing to
      increase in popularity. Neuromodulators and hyaluronic acid gel fillers have been
      shown to be well tolerated and efficacious nonsurgical alternatives in periocular
      rejuvenation.

PMID- 24926575
TI  - A new philosophy for schizophrenia care.

PMID- 24926576
TI  - Nefazodone: An update.
AB  - Nefazodone is an antidepressant with some novel characteristics in regard to its
      putative mechanism of action. Although the clinical significance of these
      properties is not clear, nefazodone is unique in that it is associated with
      minimal effects on sleep architecture and sexual functioning. Use of nefazodone
      to treat anxiety disorders appears to have promise, although placebo-controlled
      studies are still needed. Nefazodone is a potent inhibitor of CYP3A4, and thus
      numerous potential drug interactions must be carefully considered in order to
      avoid potential therapeutic misadventures. Recent reports indicate that
      nefazodone can cause severe hepatic toxicity. Evaluation of hepatic function
      before, and periodically after, therapy with nefazodone is initiated would be
      prudent. Nefazodone may be an appropriate antidepressant when potential
      anxiolytic activity would be beneficial and there is a need to avoid adverse
      effects on sexual functioning or sleep architecture. 

PMID- 24926577
TI  - The role of genetics in suicide and the link with major depression and
      alcoholism.
AB  - A clear genetic influence in suicide has been established. In addition, both the
      serotonergic and noradrenergic systems appear to have a role in suicide, mood
      disorders and alcoholism. This paper reviews some of the genes that may possibly
      be involved in suicide and their link to major depression and alcoholism. The
      genes that are reviewed act on various enzymes within the serotonergic and
      catecholaminergic systems. With further study, these entities may form a spectrum
      along the same disease process associated with variable expressivity of the
      responsible genes. 

PMID- 24926578
TI  - Depression therapy: Future prospects.
AB  - Current biological approaches to the treatment of depression focus mainly on
      modification of monoaminergic neurotransmission. New agents targeting these
      neurotransmitters are under development. Many novel antidepressant targets are
      however under investigation. These include the neurokinins, glutamate,
      purinoceptors, opioids and trophic factors. While many of these potential targets
      are likely to fail clinical development, exciting novel therapeutic options are
      likely to emerge. 

PMID- 24926579
TI  - The long-term effect of quetiapine (Seroquel TM ) monotherapy on weight in
      patients with schizophrenia.
AB  - INTRODUCTION: Quetiapine (Seroquel TM ) is an atypical antipsychoticdrug with
      demonstrated efficacy and tolerability. In particular, placebo-level
      extrapyramidal symptoms (EPS) across the entire dose range and a low propensity
      to cause sexual dysfunction suggest it may be associated with greater patient
      acceptability than alternative treatments. However, other side-effects, such as
      weight gain, may also have a significant impact on treatment acceptability.
      METHOD: We report the long-term weight changes observed in a cohort of 427
      patients with schizophrenia from controlled and open-label extension (OLE)
      trials, in which quetiapine (mean dose 475 mg/day after 1 year) was the only
      antipsychotic medication during the OLE period. RESULTS: In these patients, there
      was no overall effect on weight across the body mass index (BMI) spectrum. There
      were no dose-related effects on weight, and only one patient withdrew from
      treatment due to an adverse event of weight gain. Quetiapine appeared to have a
      weightneutral or 'normalizing' effect, with a tendency towards favourable shifts
      in bodyweight in underweight patients (BMI<18.5 kg/m 2 ) and severely obese
      patients (BMI>35 kg/m 2 ). CONCLUSION: These results indicate that long-term
      weight changes with quetiapine monotherapy are minimal and potentially
      beneficial, and do not appear to raise the medical concerns associated with some
      other atypical agents.

PMID- 24926580
TI  - The selective noradrenaline re-uptake inhibitor reboxetine has an early onset of
      antidepressant action.
AB  - INTRODUCTION: Most antidepressants take several weeks to demonstrate a
      therapeutic effect. We examined the time to onset of action of reboxetine, a
      unique selective noradrenaline re-uptake inhibitor (selective NRI). METHODS: In a
      multinational, multicentre, double-blind, parallel-group study, 56 inpatients
      with major depression were randomized to receive placebo or reboxetine titrated
      to 10 mg/day for 6 weeks. Efficacy was principally assessed by the Hamilton
      Depression Rating Scale. RESULTS: Reboxetine was associated with a significantly
      greater reduction in mean HAM-D total score from baseline to last assessment when
      compared with placebo. The effect of reboxetine separated from placebo at day 10
      (P=0.006), indicated an early onset. In accordance with this observation,
      individual HAM-D item scores early showed significant improvements among patients
      treated with reboxetine when compared with those who received placebo: mood
      improved by day 10 (P=0.004), insomnia and interest in work and daily activities
      by day 14 (P=0.006 and 0.003, respectively) and somatic symptoms and anxiety by
      day 21 (P<0.001 in both cases). CONCLUSION: Reboxetine is an effective
      antidepressant with an early onset of action. Depressed mood is relieved first,
      followed by an improvement in interest in daily activities.

PMID- 24926581
TI  - The safety and efficacy of zotepine in the treatment of schizophrenia: Results of
      a one-year naturalistic clinical trial.
AB  - INTRODUCTION AND METHOD: The safety and efficacy of zotepine,75 &#45 450 mg/day,
      were evaluated in an open multicentre one-year study in patients suffering from
      acute exacerbation of schizophrenia; total exposure amounted to 152.78 years.
      RESULTS: Mean BPRS total score was reduced from 51.7 at baseline to 40.8 at end
      point (P<0.05). Similar significant reductions at all study time-points were
      recorded for BPRS total and subscores, CGI severity and improvement, BAS total
      scores and SANS total and global scores. Significant improvements in EPMS and
      AIMS were recorded from week 12 to end-point. Clinically significant improvements
      in acute symptoms, detected early in the study, were maintained to end-point.
      CONCLUSION: Zotepine was well tolerated: weight gain, reduced serum uric acid,
      raised liver enzymes and increased heart rate were associated with chronic
      zotepine treatment. Seven patients experienced seizures during the study,
      although concomitant medications and a known historical predisposition to seizure
      are factors likely to have contributed to these events. The improvements in
      negative symptoms and low propensity to cause further extrapyramidal side-effects
      support the importance of zotepine in maintenance treatment.

PMID- 24926582
TI  - Out of sight, out of mind: Female sexuality and the care plan approach in
      psychiatric inpatients.
AB  - INTRODUCTION: This study examines how often issues surrounding sexuality were
      taken into account when managing 56 women inpatients of reproductive age. METHOD:
      Examination of the records of women discharged from the psychiatric wards of a
      hospital. RESULTS: 80% for whom there was no mention of contraceptive usage were
      taking at least one drug that is inadvisable in pregnancy, and 53% of this group
      had an identified sexual partner. There was a lack of recorded data on other
      aspects of sexual health. When children were mentioned in the admitting history,
      details were incomplete. CONCLUSION: It is argued that a thorough approach to
      assessment and care planning is needed in this population.

PMID- 24926583
TI  - Sexual dysfunction in depressed patients undergoing treatment with
      antidepressants.
AB  - INTRODUCTION: To determine the incidence of treatment-induced sexual dysfunction
      in depressed outpatients treated with five different antidepressants. METHODS:
      100 depressed patients (ICD-10 criteria for depressive episode, recurrent
      depressive disorder, and dysthymia) with an active sex life were assessed by the
      MADS, the CGI, and the Sexual Function Questionnaire at baseline and at 1, 2, and
      4 months. RESULTS: Although the sample showed a slight improvement, generally, in
      sexual functioning after 4 months treatment, there were several cases of
      deterioration. CONCLUSIONS: Greatest interefernce with sexual functioning occurs
      with paroxetine, venlafaxine, and clomipramine.

PMID- 24926584
TI  - Relationship of akathisia to aggressive and self-injurious behaviour: A
      prevalence study in a UK tertiary referral centre.
AB  - INTRODUCTION: Akathisia is a common and distressing side-effect associated with
      antipsychotic drug administration. The relationship between akathisia and five
      forms of expressed aggression is investigated. METHOD: Sixty-four mentally
      disordered patients were assessed for the point prevalence of akathisia, using
      Barnes' rating scale for drug-induced akathisia. 1 The five types of aggression
      studied were: verbal abuse/ aggression, threatening behaviour/violence, physical
      aggression, destruction of property and deliberate self-harm, all of which are
      routinely recorded for patients. RESULTS: Fourteen subjects (21.9%) experienced
      akathisia, which was approximately four times more likely to occur in women than
      in men: four (6.3%) had pseudoakathisia. Akathisia was statistically
      significantly associated with threatening behaviour (P<0.05) and physical
      aggression (P<0.05). CONCLUSION: The data provide evidence for a relationship
      between the experience of akathisia and the expression of two forms of aberrant
      behaviour.

PMID- 24926585
TI  - Psychiatric inpatients' satisfaction with services: A pilot study.
AB  - INTRODUCTION: Fifty-three patients admitted to a psychiatric inpatient unit in
      South London were interviewed to ascertain their satisfaction with services
      provided for them. METHOD: The level of satisfaction with various aspects of
      treatment was evaluated using a 45-item questionnaire. RESULTS: Results showed
      that patients were generally satisfied with the staff attitudes and care,
      although two-thirds felt that they had not been sufficiently involved in their
      own treatment planning. Younger patients reported more frequent difficulties in
      the relationship with staff. Patients were generally satisfied with the physical
      environment. Patients with a higher number of previous admissions were more
      satisfied with the planning of care, and they were less often in conflict with
      the staff. Patients admitted compulsorily were less satisfied than voluntary
      patients with the overall quality of the help received and said they would rarely
      re-contact the service in the future. There was virtually no effect of ethnicity
      on the levels of satisfaction in different aspects of care. The only worry
      expressed more frequently by African-Caribbean patients was about re-contacting
      the service in the future, even though they felt the help received in planning
      their discharge was good. CONCLUSION: It would be useful to carry out such
      surveys more often.

PMID- 24926586
TI  - Olanzapine-induced mania.
AB  - This report describes a case of manic symptoms induced by olanzapine in an 85
      year-old female with a 3 year history of delusional disorder. She was treated in
      the past with trifluoperazine and risperidone. Symptoms were severe enough to
      require detention in hospital. Florid manic symptoms resolved two weeks after
      stopping olanzapine while only using 1 mg of haloperidol as required. 

PMID- 24926587
TI  - Oskar Panizza: Psychiatrist, antipsychiatrist, patient The man behind Emil
      Kraepelin's case report on 'paraphrenias'.
AB  - A contemporary of Emil Kraepelin, Oskar Panizza was a psychiatric trainee under
      Bernhard von Gudden at the Oberbayerische Kreisirrenanstalt Munchen. While
      participating in Gudden's famous degeneration studies, Panizza became psychotic.
      He quit his job and became a writer, trying to cope with psychotic episodes by
      publishing literary works. Most of his works were confiscated and Panizza himself
      was locked up and persecuted. His experience of his psychotic symptoms made him
      critical of the psychiatric orthodoxy of the time, and he preached a kind of
      psychological psychiatry that anticipated important features of the
      Antipsychiatry movement of the 1970s. After serving a year in prison for his
      writings, Panizza left Germany and went to Zurich, Switzerland. In 1898 he was
      deported from Switzerland and went to Paris, where his book of poems, Parisiana
      and his money were confiscated. In 1901 he had to return to the Oberbayerische
      Kreisirrenanstalt where a diagnosis of paranoia was made. Then he lived in Paris
      for the next three years, but his psychotic symptoms worsened and he fled back to
      the Oberbayerische Kreisirrenanstalt, where he was examined by Prof. Gudden, Dr.
      Ungemach and by his former colleague Emil Kraepelin, who had become head of
      department. The encounters with Oskar Panizza gave Emil Kraepelin some of the
      ideas on which he developed his concept of 'paraphrenias' and in Lectures on
      Clinical Psychiatry , Kraepelin illustrated the 'systematic paraphrenias', by the
      life of his former colleague Oskar Panizza who died in hospital in Bayreuth in
      1921. 

PMID- 24926588
TI  - A patient who changed my practice: Herb Kern, the first light therapy patient.
AB  - This paper presents the case of Herb Kern, the first patient with clear-cut
      seasonal mood cycles in whom light therapy was used to reverse depression. His
      successful treatment was an inspiration to the author to define the syndrome of
      Seasonal Affective Disorder (SAD) and use light therapy as a systematic
      controlled treatment for this condition. This is an example of how a single
      patient can lead to the recognition of a common condition and a novel treatment
      modality. 

PMID- 24926589
TI  - Chronic fatigue syndrome.

PMID- 24926593
TI  - Structural heterogeneity in transmembrane amyloid precursor protein homodimer is
      a consequence of environmental selection.
AB  - The 99 amino acid C-terminal fragment of amyloid precursor protein (C99),
      consisting of a single transmembrane (TM) helix, is known to form homodimers.
      Homodimers can be processed by gamma-secretase to produce amyloid-beta (Abeta)
      protein, which is implicated in Alzheimer's disease (AD). While knowledge of the
      structure of C99 homodimers is of great importance, experimental NMR studies and
      simulations have produced varying structural models, including right-handed and
      left-handed coiled-coils. In order to investigate the structure of this critical
      protein complex, simulations of the C99(15-55) homodimer in POPC membrane bilayer
      and DPC surfactant micelle environments were performed using a multiscale
      approach that blends atomistic and coarse-grained models. The C99(15-55)
      homodimer adopts a dominant right-handed coiled-coil topology consisting of three
      characteristic structural states in a bilayer, only one of which is dominant in
      the micelle. Our structural study, which provides a self-consistent framework for
      understanding a number of experiments, shows that the energy landscape of the C99
      homodimer supports a variety of slowly interconverting structural states. The
      relative importance of any given state can be modulated through environmental
      selection realized by altering the membrane or micelle characteristics.

PMID- 24926594
TI  - Correspondence.

PMID- 24926595
TI  - Reply: To PMID 23609127.

PMID- 24926596
TI  - Improved 4-chlorophenol dechlorination at biocathode in bioelectrochemical system
      using optimized modular cathode design with composite stainless steel and carbon
      based materials.
AB  - This study developed and optimized a modular biocathode materials design in
      bioelectrochemical system (BES) using composite metal and carbon-based materials.
      The 4-chlorophenol (4-CP) dechlorination could be improved with such composite
      materials. Results showed that stainless steel basket (SSB) filled with graphite
      granules (GG) and carbon brush (CB) (SSB/GG/CB) was optimum for dechlorination,
      followed by SSB/CB and SSB/GG, with rate constant k of 0.0418 +/- 0.0002, 0.0374
      +/- 0.0004, and 0.0239 +/- 0.0002 h(-1), respectively. Electrochemical impedance
      spectroscopy (EIS) demonstrated that the composite materials with metal can
      benefit the electron transfer and decrease the charge transfer resistance to be
      80.4 Omega in BES-SSB/GG/CB, much lower than that in BES-SSB (1674.3 Omega), BES
      GG (387.3 Omega), and BES-CB (193.8 Omega). This modular cathode design would be
      scalable with successive modules for BES scale-up, and may offer useful
      information to guide the selection and design of BES materials towards
      dechlorination improvement in wastewater treatment.

PMID- 24926597
TI  - Ammonia inhibition on Arthrospira platensis in relation to the initial biomass
      density and pH.
AB  - In this study the combined effect of total ammoniacal nitrogen (TAN)
      concentration, initial biomass density and initial pH of the cultivation medium
      on growth of Arthrospira platensis was studied. The results indicate that TAN
      inhibition in relation to the initial biomass in unregulated pH cultures is
      neither a clearly biomass-independent nor biomass-dependent phenomenon. However,
      low biomass densities are more susceptible to ammonia inhibition than higher
      biomass densities. Higher biomass densities seems to mitigate ammonia inhibition
      through rapider assimilation of TAN. In all cases studied the growth rates were
      lower compared to the cultures with nitrate as nitrogen source. It was observed
      that at low TAN concentration, although no ammonia inhibition occured the growth
      rates were decreased due to nitrogen limitation. Low TAN concentration triggered
      the accumulation of carbohydrates affecting thus significantly the biomass
      composition. Ammonia losses from the cultivation system were also determined.
      Ammonia losses ranged between 17% and 80%. 

PMID- 24926598
TI  - Algae harvesting for biofuel production: influences of UV irradiation and
      polyethylenimine (PEI) coating on bacterial biocoagulation.
AB  - There is a pressing need to develop efficient and sustainable separation
      technologies to harvest algae for biofuel production. In this work, two bacterial
      species (Escherichia coli and Rhodococus sp.) were used as biocoagulants to
      harvest Chlorella zofingiensis and Scenedesmus dimorphus. The influences of UV
      irradiation and polyethylenimine (PEI)-coating on the algal harvesting efficiency
      were investigated. Results showed that the UV irradiation could slightly enhance
      bacteria-algae biocoagulation and algal harvesting efficiency. In contrast, the
      PEI-coated E. coli cells noticeably increased the harvesting efficiencies from
      23% to 83% for S. dimorphus when compared to uncoated E. coli cells. Based on the
      soft-particle Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, an energy barrier
      existed between uncoated E. coli cells and algal cells, whereas the PEI coating
      on E. coli cells eliminated the energy barrier, thereby the biocoagulation was
      significantly improved. Overall, this work presented groundwork toward the
      potential use of bacterial biomass for algal harvesting from water. 

PMID- 24926599
TI  - System and method for research-scale outdoor production of microalgae and
      cyanobacteria.
AB  - Eukaryotic microalgae and cyanobacteria have recently reemerged as promising
      organisms in the effort to develop sustainable options for production of food and
      fuel. However, substantial discrepancies consistently arise between laboratory
      and outdoor cultivation, and gains demonstrated using laboratory technologies
      have not paralleled gains observed in field demonstrations. For these reasons, a
      low-maintenance system and process for research-scale outdoor cultivation of a
      variety of both freshwater and marine microalgae and cyanobacteria was developed.
      Nine genera were evaluated in the system, demonstrating cultivation of both
      laboratory model and commercial-production organisms. Hundreds to thousands of
      grams of dry biomass could be produced in a single growth cycle, suitable for a
      variety of uses including inoculum generation, protein production, and biofuel
      applications. Following testing in outdoor stock-ponds, Scenedesmus and
      Nannochloropsis were grown semi-continuously in an 8000 L airlift-driven raceway,
      yielding in total over 8 kg of dry biomass for each strain.

PMID- 24926600
TI  - Combined process for ethanol fermentation at high-solids loading and biogas
      digestion from unwashed steam-exploded corn stover.
AB  - A combined process was designed for the co-production of ethanol and methane from
      unwashed steam-exploded corn stover. A terminal ethanol titer of 69.8 g/kg mass
      weight (72.5%) was achieved when the fed-batch mode was performed at a final
      solids loading of 35.5% (w/w) dry matter (DM) content. The whole stillage from
      high-solids ethanol fermentation was directly transferred in a 3-L anaerobic
      digester. During 52-day single-stage digester operation, the methane productivity
      was 320 mL CH4/g volatile solids (VS) with a maximum VS reduction efficiency of
      55.3%. The calculated overall product yield was 197 g ethanol + 96 g methane/kg
      corn stover. This indicated that the combined process was able to improve overall
      content utilization and extract a greater yield of lignocellulosic biomass
      compared to ethanol fermentation alone.

PMID- 24926601
TI  - Monitoring of thermophilic adaptation of mesophilic anaerobe fermentation of
      sugar beet pressed pulp.
AB  - Anaerobe fermentation of sugar beet pressed pulp was investigated in pilot-scale
      digesters. Thermophilic adaptation of mesophilic culture was monitored using
      chemical analysis and metagenomic characterization of the sludge. Temperature
      adaptation was achieved by increasing the temperature gradually (2  degrees C
      day(-1)) and by greatly decreasing the OLR. During stable run, the OLR was
      increased gradually to 11.29 kg VS m(-3)d(-1) and biogas yield was 5% higher in
      the thermophilic reactor. VFA levels increased in the thermophilic reactor with
      increased OLR (acetic acid 646 mg L(-1), propionic acid 596 mg L(-1)), then VFA
      decreased and the operation was manageable beside the relative high tVFA (1300
      2000 mg L(-1)). The effect of thermophilic adaptation on the microbial
      communities was studied using a sequencing-based metagenomic approach.
      Connections between physico-chemical parameters and populations of bacteria and
      methanogen archaea were revealed.

PMID- 24926602
TI  - Fouling mechanisms of gel layer in a submerged membrane bioreactor.
AB  - The fouling mechanisms underlying gel layer formation and its filtration
      resistance in a submerged membrane bioreactor (MBR) were investigated. It was
      found that gel layer rather than cake layer was more easily formed when soluble
      microbial products content in sludge suspension was relatively high.
      Thermodynamic analyses showed that gel layer formation process should overcome a
      higher energy barrier as compared with cake layer formation process. However,
      when separation distance <2.3 nm, attractive interaction energy of gelling
      foulant-membrane combination was remarkably higher than that of sludge floc
      membrane combination. The combined effects were responsible for gel layer
      formation. Filtration tests showed that specific filtration resistance (SFR) of
      gel layer was almost 100 times higher than that of cake layer. The unusually high
      SFR of gel layer could be ascribed to the gelling propensity and osmotic pressure
      mechanism. These findings shed significant light on fouling mechanisms of gel
      layer in MBRs.

PMID- 24926603
TI  - Pyrolysis condition affected sulfamethazine sorption by tea waste biochars.
AB  - Sulfamethazine (SMT) as a veterinary drug has been detected frequently in the
      environment. In this study, six biochars produced from tea waste (TW) at 300 and
      700  degrees C with or without N2 and steam activation were characterized and
      evaluated for SMT sorption in water. The sorption of SMT was interpreted as a
      function of biochar production condition, SMT concentration, pH and
      physicochemical characteristics of biochar. Distribution coefficient data showed
      high sorption of SMT at low pH (~3) and the highest sorption density of 33.81 mg
      g(-1) was achieved by the steam activated biochar produced at 700  degrees C. The
      steam activation process increased the adsorption capacity by increasing the
      surface area of the biochar. The pi-pi electron donor-acceptor interaction,
      cation-pi interaction and cation exchange at low pH were the primary mechanisms
      governing SMT retention by biochars. Overall, steam activated tea waste biochar
      could be a promising remedy of SMT removal from water.

PMID- 24926604
TI  - Effects of catalysts and solvents on liquefaction of Onopordum heteracanthum for
      production of bio-oils.
AB  - Milled Onopordum heteracanthum stalks were converted to liquid products in
      organic solvents (methanol, ethanol and acetone) with (KOH and ZnCl2) and without
      catalyst in an autoclave at temperatures of 523, 543 and 563 K. Effects of
      liquefaction parameters such as catalyst and solvent were investigated. The
      percentage yields from supercritical methanol, ethanol and acetone conversions
      were 48.2, 50.4 and 66.2 at 563 K in the non-catalytic runs, respectively. In the
      catalytic run with ZnCl2, the highest conversion (70.2%) was obtained in acetone
      at the same temperature. The obtained liquid products at 563 K were analyzed and
      characterized by elemental, Fourier transform infrared spectroscopy, gas
      chromatography-mass spectrometry. 106 different compounds have been identified by
      GC-MS in the liquid products obtained in methanol at 563 K.

PMID- 24926605
TI  - Anaerobic co-digestion of steam-treated Quercus serrata chips and sewage sludge
      under mesophilic and thermophilic conditions.
AB  - The biodegradation of Quercus serrata chips was evaluated by anaerobic digestion
      under various steam explosion conditions. In continuous experiments, untreated
      chips (W0) and chips steam-treated at less than 1.0 MPa (W1) and 2.0 MPa (W4)
      were co-digested with sewage sludge (S1 and S2) taken from two different
      wastewater treatment plants. The apparent methane yield of W1 and W4 co-digested
      with S1 (thermophilic) was 261 dm(3)/kgVS (volatile solids) and 248 dm(3)/kgVS,
      respectively. The apparent methane yield of W4 co-digested with S2 was 258
      dm(3)/kgVS (mesophilic) and 271 dm(3)/kgVS (thermophilic). Methane production was
      inhibited by W0 due to components released during hydrolysis. The methane
      conversion ratio of pretreated chips obtained in batch experiments varied from
      40.5% to 53.8% (mesophilic) and from 49.0% to 63.7% (thermophilic). The methane
      conversion ratio increased with decreasing acid-soluble lignin content in the
      chips.

PMID- 24926606
TI  - Sustainable organic loading rate and energy recovery potential of mesophilic
      anaerobic membrane bioreactor for municipal wastewater treatment.
AB  - The overall performance of a mesophilic anaerobic membrane bioreactor (AnMBR) for
      synthetic municipal wastewater treatment was investigated under a range of
      organic loading rate (OLR). A very steady and high chemical oxygen demand (COD)
      removal (around 98%) was achieved over a broad range of volumetric OLR of 0.8-10
      gCOD/L/d. The sustainable volumetric and sludge OLR satisfying a permeate COD
      below 50 mg/L for general reuse was 6 gCOD/L/d and 0.63 gCOD/gMLVSS (mixed liquor
      volatile suspended solids)/d, respectively. At a high sludge OLR of over 0.6
      gCOD/gMLVSS/d, the AnMBR achieved high methane production of over 300 ml/gCOD
      (even approaching the theoretical value of 382 ml/gCOD). A low biomass production
      of 0.015-0.026 gMLVSS/gCOD and a sustainable flux of 6L/m(2)/h were observed. The
      integration of a heat pump and forward osmosis into the mesophilic AnMBR process
      would be a promising way for net energy recovery from typical municipal
      wastewater in a temperate area.

PMID- 24926607
TI  - Production of adsorbents by pyrolysis of paper mill sludge and application on the
      removal of citalopram from water.
AB  - This work describes the production of alternative adsorbents from industrial
      residues and their application for the removal of a highly consumed
      antidepressant (citalopram) from water. The adsorbents were produced by pyrolysis
      of both primary and biological paper mill sludge at different temperatures and
      residence times. The original sludge and the produced chars were fully
      characterized by elemental and proximate analyses, total organic carbon, specific
      surface area (BET), N2 isotherms, FTIR, (13)C and (1)H solid state NMR and SEM.
      Batch kinetic and equilibrium experiments were carried out to describe the
      adsorption of citalopram onto the produced materials. The fastest kinetics and
      the highest adsorption capacity were obtained using primary sludge pyrolysed at
      800  degrees C during 150 min. The use of pyrolysed paper mill sludge for the
      remediation of contaminated waters might constitute an interesting application
      for the valorization of those wastes.

PMID- 24926608
TI  - Characterization of endolithic cyanobacterial strain, Leptolyngbya sp. ISTCY101,
      for prospective recycling of CO2 and biodiesel production.
AB  - The present investigation evaluates the potential of an endolithic cyanobacterium
      isolated from marble rock to utilize sodium bicarbonate (NaHCO3) as carbon source
      for prospective recycling of CO2 into biodiesel. Microalgae thriving on marble
      were cultured and subjected to increasing NaHCO3 concentration. The most
      competent isolate was identified and characterized in terms of growth, lipid
      content and fatty acid profile. A semicontinuous mesh incubator was designed for
      biofilm development. Isolate ISTCY101 was identified as Leptolyngbya sp. by 16S
      rRNA sequencing. Leptolyngbya ISTCY101 efficiently used BG-11 (50 mM NaHCO3) and
      artificial seawater medium (25 gL(-1) NaCl) with biomass productivity 78.9 and
      75.74 mg L(-1)d(-1), respectively. Maximum areal biomass productivity of 2.01 gm(
      2)d(-1) was recorded in the mesh incubator, with complete exclusion of
      centrifugation for harvesting. Lipid content varied from 16% to 21%, consisting
      predominantly of C16:0, C16:1, C18:0, C18:1 fatty acids (>60%) making promising
      feedstock for biodiesel production.

PMID- 24926609
TI  - Hyperexponential and nonmonotonic retention of polyvinylpyrrolidone-coated silver
      nanoparticles in an Ultisol.
AB  - The increasing application of engineered nanoparticles (ENPs) has heightened the
      concern that these ENPs would eventually be released to the environment and may
      enter into life cycle of living beings. In this regard, it is essential to
      understand how these ENPs transport and retain in natural soils because they are
      considered to be a major repository for ENPs. Herein, transport and retention of
      polyvinylpyrrolidone (PVP)-coated silver nanoparticles (PVP-AgNPs) were
      investigated over a wide range of physicochemical factors in water-saturated
      columns packed with an Ultisol rich in clay-size particles. Higher mobility of
      PVP-AgNPs occurred at larger soil grain size, lower solution ionic strength and
      divalent cation concentration, higher flow rate, and greater PVP concentrations.
      Most breakthrough curves (BTCs) for PVP-AgNPs exhibited significant amounts of
      retardation in the soil due to its large surface area and quantity of retention
      sites. In contrast to colloid filtration theory, the shapes of retention profiles
      (RPs) for PVP-AgNPs were either hyperexponential or nonmonotonic (a peak in
      particle retention down-gradient from the column inlet). The BTCs and
      hyperexponential RPs were successfully described using a 1-species model that
      considered time- and depth-dependent retention. Conversely, a 2-species model
      that included reversibility of retained PVP-AgNPs had to be employed to better
      simulate the BTCs and nonmonotonic RPs. As the retained concentration of species
      1 approached the maximum solid-phase concentration, a second mobile species
      (species 2, i.e., the same PVP-AgNPs that are reversibly retained) was released
      that could be retained at a different rate than species 1 and thus yielded the
      nonmonotonic RPs. Some retained PVP-AgNPs were likely to irreversibly deposit in
      the primary minimum associated with microscopic chemical heterogeneity (favorable
      sites). Transmission electron microscopy and energy-dispersive X-ray spectroscopy
      analysis suggested that these favorable sites were positively charged sites on
      montmorillonite edges and goethite surfaces in the soil. Overall, our study
      highlights that the transport and especially retention of PVP-AgNPs are highly
      sensitive to the physicochemical factors, but mathematical modeling can
      accurately predict the fate of these ENPs in porous media which is important for
      better understanding the fate of these ENPs in point of exit and in the
      environment. 

PMID- 24926610
TI  - Chemical vapor deposition growth of single-walled carbon nanotubes with
      controlled structures for nanodevice applications.
AB  - Single-walled carbon nanotubes (SWNTs), a promising substitute to engineer
      prospective nanoelectronics, have attracted much attention because of their
      superb structures and physical properties. The unique properties of SWNTs rely
      sensitively on their specific chiral structures, including the diameters, chiral
      angles, and handedness. Furthermore, high-performance and integrated circuits
      essentially require SWNT samples with well-aligned arrays, of single conductive
      type and of pure chirality. Although much effort has been devoted to chemical
      vapor deposition (CVD) growth of SWNTs, their structure control, growth
      mechanism, and structural characterizations are still the primary obstacles for
      the fabrication and application of SWNT-based nanodevices. In this Account, we
      focus on our established CVD growth methodology to fulfill the requirements of
      nanodevice applications. A rational strategy was successfully exploited to
      construct complex architectures, selectively enrich semiconducting (s) or
      metallic (m) SWNTs, and control chirality. First, well-aligned and highly dense
      SWNT arrays are beneficial for nanodevice integration. For the directed growth
      mode, anisotropic interactions between the SWNTs and the crystallographic
      structure of substrate are crucial for their growth orientation. Just as crystals
      possess various symmetries, SWNTs with controlled geometries have the
      corresponding turning angles. Their complex architectures come from the
      synergetic effect of lattice and gas flow directed modes. Especially, the aligned
      orientations of SWNTs on graphite are chirality-selective, and their chiral
      angles, handedness, and (n,m) index have been conveniently and accurately
      determined. Second, UV irradiation and sodium dodecyl sulfate (SDS) washing-off
      methods have been explored to selectively remove m-SWNTs, leaving only s-SWNT
      arrays on the surface. Moreover, the UV-assisted technique takes the advantages
      of low cost and high efficiency and it directly produces a high ratio of s-SWNT
      arrays. We also designed a smart scotch tape to sort out the s-SWNTs and m-SWNTs
      from the as-grown mixture with 3-aminopropyl-triethoxysilane and
      triethoxyphenylsilane as glues, respectively. This is analogous to the mechanical
      exfoliation of a graphene sheet. Third, the obtained SWNT intramolecular
      junctions obtained by temperature-mediated CVD indicate that temperature can
      seriously affect the SWNT's chirality during its growth. Importantly, the cloning
      method can validate the chirality-controlled growth of SWNTs, and the cloning
      efficiency is significantly improved on a quartz surface. Well-aligned SWNT
      arrays with a high density and controlled structures are highly desirable for
      carbon nanoelectronics. We hope that the advanced methodology used here will
      promote their controlled preparation and provide insights into the growth
      mechanism of SWNTs.

PMID- 24926611
TI  - Plasmonic color palettes for photorealistic printing with aluminum
      nanostructures.
AB  - We introduce the first plasmonic palette utilizing color generation strategies
      for photorealistic printing with aluminum nanostructures. Our work expands the
      visible color space through spatially mixing and adjusting the nanoscale spacing
      of discrete nanostructures. With aluminum as the plasmonic material, we achieved
      enhanced durability and dramatically reduced materials costs with our
      nanostructures compared to commonly used plasmonic materials such as gold and
      silver, as well as size regimes scalable to higher-throughput approaches such as
      photolithography and nanoimprint lithography. These advances could pave the way
      toward a new generation of low-cost, high-resolution, plasmonic color printing
      with direct applications in security tagging, cryptography, and information
      storage. 

PMID- 24926612
TI  - Does isolated traumatic subarachnoid hemorrhage merit a lower intensity level of
      observation than other traumatic brain injury?
AB  - Evidence is emerging that isolated traumatic subarachnoid hemorrhage (ITSAH) may
      be a milder form of traumatic brain injury (TBI). If true, ITSAH may not benefit
      from intensive care unit (ICU) admission, which would, in turn, decrease resource
      utilization. We conducted a retrospective review of all TBI admissions to our
      institution between February 2010 and November 2012 to compare the presentation
      and clinical course of subjects with ITSAH to all other TBI. We then performed
      descriptive statistics on the subset of ITSAH subjects presenting with a Glasgow
      Coma Score (GCS) of 13-15. Of 698 subjects, 102 had ITSAH and 596 had any other
      intracranial hemorrhage pattern. Compared to all other TBI, ITSAH had
      significantly lower injury severity scores (p<0.0001), lower head abbreviated
      injury scores (p<0.0001), higher emergency department GCS (p<0.0001), shorter ICU
      stays (p=0.007), higher discharge GCS (p=0.005), lower mortality (p=0.003), and
      significantly fewer head computed tomography scans (p<0.0001). Of those ITSAH
      subjects presenting with a GCS of 13-15 (n=77), none underwent placement of an
      intracranial monitor or craniotomy. One subject (1.3%) demonstrated a change in
      exam (worsened headache and dizziness) concomitant with a progression of his
      intracranial injury. His symptoms resolved with readmission to the ICU and
      continued observation. Our results suggest that ITSAH are less-severe brain
      injuries than other TBI. ITSAH patients with GCS scores of 13-15 demonstrate low
      rates of clinical progression, and when progression occurs, it resolves without
      further intervention. This subset of TBI patients does not appear to benefit from
      ICU admission.

PMID- 24926614
TI  - Early exposure of murine embryonic stem cells to hematopoietic cytokines
      differentially directs definitive erythropoiesis and cardiomyogenesis in alginate
      hydrogel three-dimensional cultures.
AB  - HepG2-conditioned medium (CM) facilitates early differentiation of murine
      embryonic stem cells (mESCs) into hematopoietic cells in two-dimensional cultures
      through formation of embryoid-like colonies (ELCs), bypassing embryoid body (EB)
      formation. We now demonstrate that three-dimensional (3D) cultures of alginate
      encapsulated mESCs cultured in a rotating wall vessel bioreactor can be
      differentially driven toward definitive erythropoiesis and cardiomyogenesis in
      the absence of ELC formation. Three groups were evaluated: mESCs in maintenance
      medium with leukemia inhibitory factor (LIF, control) and mESCs cultured with
      HepG2 CM (CM1 and CM2). Control and CM1 groups were cultivated for 8 days in
      early differentiation medium with murine stem cell factor (mSCF) followed by 10
      days in hematopoietic differentiation medium (HDM) containing human
      erythropoietin, m-interleukin (mIL)-3, and mSCF. CM2 cells were cultured for 18
      days in HDM, bypassing early differentiation. In CM1, a fivefold expansion of
      hematopoietic colonies was observed at day 14, with enhancement of erythroid
      progenitors, hematopoietic genes (Gata-2 and SCL), erythroid genes (EKLF and beta
      major globin), and proteins (Gata-1 and beta-globin), although zeta-globin was
      not expressed. In contrast, CM2 primarily produced beating colonies in standard
      hematopoietic colony assay and expressed early cardiomyogenic markers, anti
      sarcomeric alpha-actinin and Gata-4. In conclusion, a scalable, automatable,
      integrated, 3D bioprocess for the differentiation of mESC toward definitive
      erythroblasts has been established. Interestingly, cardiomyogenesis was also
      directed in a specific protocol with HepG2 CM and hematopoietic cytokines making
      this platform a useful tool for the study of erythroid and cardiomyogenic
      development. 

PMID- 24926615
TI  - Glycine receptors control the generation of projection neurons in the developing
      cerebral cortex.
AB  - The development of the cerebral cortex requires coordinated regulation of
      proliferation, specification, migration and differentiation of cortical
      progenitors into functionally integrated neurons. The completion of the
      neurogenic program requires a dynamic interplay between cell intrinsic regulators
      and extrinsic cues, such as growth factor and neurotransmitters. We previously
      demonstrated a role for extrasynaptic glycine receptors (GlyRs) containing the
      alpha2 subunit in cerebral cortical neurogenesis, revealing that endogenous GlyR
      activation promotes interneuron migration in the developing cortical wall. The
      proliferative compartment of the cortex comprises apical progenitors that give
      birth to neurons directly or indirectly through the generation of basal
      progenitors, which serve as amplification step to generate the bulk of cortical
      neurons. The present work shows that genetic inactivation of Glra2, the gene
      coding the alpha2 subunit of GlyRs, disrupts dorsal cortical progenitor
      homeostasis with an impaired capability of apical progenitors to generate basal
      progenitors. This defect results in an overall reduction of projection neurons
      that settle in upper or deep layers of the cerebral cortex. Overall, the
      depletion of cortical neurons observed in Glra2-knockout embryos leads to
      moderate microcephaly in newborn Glra2-knockout mice. Taken together, our
      findings support a contribution of GlyR alpha2 to early processes in cerebral
      cortical neurogenesis that are required later for the proper development of
      cortical circuits. 

PMID- 24926616
TI  - Modulation of p53beta and p53gamma expression by regulating the alternative
      splicing of TP53 gene modifies cellular response.
AB  - In addition to the tumor suppressor p53 protein, also termed p53alpha, the TP53
      gene produces p53beta and p53gamma through alternative splicing of exons 9beta
      and 9gamma located within TP53 intron 9. Here we report that both TG003, a
      specific inhibitor of Cdc2-like kinases (Clk) that regulates the alternative
      splicing pre-mRNA pathway, and knockdown of SFRS1 increase expression of
      endogenous p53beta and p53gamma at mRNA and protein levels. Development of a TP53
      intron 9 minigene shows that TG003 treatment and knockdown of SFRS1 promote
      inclusion of TP53 exons 9beta/9gamma. In a series of 85 primary breast tumors, a
      significant association was observed between expression of SFRS1 and alpha
      variant, supporting our experimental data. Using siRNA specifically targeting
      exons 9beta/9gamma, we demonstrate that cell growth can be driven by modulating
      p53beta and p53gamma expression in an opposite manner, depending on the cellular
      context. In MCF7 cells, p53beta and p53gamma promote apoptosis, thus inhibiting
      cell growth. By transient transfection, we show that p53beta enhanced p53alpha
      transcriptional activity on the p21 and Bax promoters, while p53gamma increased
      p53alpha transcriptional activity on the Bax promoter only. Moreover, p53beta and
      p53gamma co-immunoprecipitate with p53alpha only in the presence of p53
      responsive promoter. Interestingly, although p53beta and p53gamma promote
      apoptosis in MCF7 cells, p53beta and p53gamma maintain cell growth in response to
      TG003 in a p53alpha-dependent manner. The dual activities of p53beta and p53gamma
      isoforms observed in non-treated and TG003-treated cells may result from the
      impact of TG003 on both expression and activities of p53 isoforms. Overall, our
      data suggest that p53beta and p53gamma regulate cellular response to modulation
      of alternative splicing pre-mRNA pathway by a small drug inhibitor. The
      development of novel drugs targeting alternative splicing process could be used
      as a novel therapeutic approach in human cancers. 

PMID- 24926617
TI  - p53-directed translational control can shape and expand the universe of p53
      target genes.
AB  - The increasing number of genome-wide transcriptome analyses focusing on p53
      induced cellular responses in many cellular contexts keeps adding to the already
      numerous p53-regulated transcriptional networks. To investigate post
      transcriptional controls as an additional dimension of p53-directed gene
      expression responses, we performed a translatome analysis through polysomal
      profiling on MCF7 cells upon 16 hours of doxorubicin or nutlin-3a treatment. The
      comparison between the transcriptome and the translatome revealed a considerable
      level of uncoupling, characterized by genes whose transcription variations did
      not correlate with translation variations. Interestingly, uncoupled genes were
      associated with apoptosis, DNA and RNA metabolism and cell cycle functions,
      suggesting that post-transcriptional control can modulate classical p53-regulated
      responses. Furthermore, even for well-established p53 targets that were
      differentially expressed both at the transcriptional and translational levels,
      quantitative differences between the transcriptome, subpolysomal and polysomal
      RNAs were evident. As we searched mechanisms underlying gene expression
      uncoupling, we identified the p53-dependent modulation of six RNA-binding
      proteins, where hnRNPD (AUF1) and CPEB4 are direct p53 transcriptional targets,
      whereas SRSF1, DDX17, YBX1 and TARDBP are indirect targets (genes modulated
      preferentially in the subpolysomal or polysomal mRNA level) modulated at the
      translational level in a p53-dependent manner. In particular, YBX1 translation
      appeared to be reduced by p53 via two different mechanisms, one related to mTOR
      inhibition and the other to miR-34a expression. Overall, we established p53 as a
      master regulator of translational control and identified new p53-regulated genes
      affecting translation that can contribute to p53-dependent cellular responses. 

PMID- 24926619
TI  - Redox-responsive copper(I) metallogel: a metal-organic hybrid sorbent for
      reductive removal of chromium(VI) from aqueous solution.
AB  - Herein, we report a new strategy to remove toxic Cr(VI) ion from aqueous solution
      using metal-organic hybrid gel as sorbent. The gel could be easily synthesized
      from the commercially available organic ligand 2-mercaptobenzimidazole (2-MBIm)
      and copper(II) chloride in alcoholic medium. The synthesis involves one-electron
      reduction of Cu(II) to Cu(I) by 2-MBIm, and then gel formation is triggered
      through Cu(I)-ligand coordination and extensive hydrogen-bonding interactions
      involving the "-NH" protons (of 2-MBIm ligand), solvent molecules, and chloride
      ions. The gel shows entangled network morphology. Different microanalytical
      techniques (FTIR, powder XRD, FESEM, TEM, rheology etc.) have been employed for
      complete characterizations of the gel sample. Both Cu(I) (in situ formed) and Cl(
      ) ions trigger the gel formation as demonstrated from systematic chemical
      analyses. The gel also exhibits its stimuli-responsive behavior toward different
      interfering chemical parameters (pH, selective metal ions and anions, selective
      complexing agents, etc.). Finally the gel shows its redox-responsive nature owing
      to the distinguished presence of Cu(I) metal centers throughout its structural
      backbone. And this indeed helps in the effective removal of Cr(VI) ions from
      aqueous solution. Reduction of Cr(VI) to Cr(III) ions and its subsequent sorption
      take place in the gel matrix. The reductive removal of Cr(VI) has been
      quantitatively interpreted through a set of different kinetic
      measurements/models, and the removal capacity of the gel matrix has been observed
      to be ~331 mg g(-1) at pH ~ 2.7, which is admirably higher than the commonly used
      adsorbents. However, the capacity decreases with the increase in pH of the
      solution. The overall removal mechanism has been clearly demonstrated. Again, the
      gel could also be recycled. Thus, the low-cost and large-scale fabrication of the
      redox-active metallogel makes it an efficient matrix for the toxic ion removal
      and hence indicates the high promise of this new generation hybrid material for
      environmental pollution abatement. 

PMID- 24926618
TI  - Nemo-like kinase is critical for p53 stabilization and function in response to
      DNA damage.
AB  - The DNA damage response (DDR) acts as a protective mechanism for maintaining cell
      homeostasis. Nemo-like kinase (NLK) is a serine/threonine-protein kinase that has
      an important role in many pathways; however, its function in the DDR has not yet
      been defined. In our study, NLK-deficient HCT116 cells were found to be resistant
      to etoposide-induced cell death. We demonstrated that NLK is required for p53
      activation in response to DNA damage. Remarkably, mechanistic studies revealed
      that NLK interacts with p53 and stabilizes p53 by blocking MDM2-mediated p53
      ubiquitination and degradation. Furthermore, NLK enhances p53 activity and
      affects expression downstream of p53. Interestingly, these functions of NLK are
      not related to its kinase activity. Consistent with these results, NLK-deficient
      cells have a resistance effect on DNA damage. Therefore, these findings emphasize
      that NLK is a novel factor in DDR mechanisms. 

PMID- 24926620
TI  - Tuning the thermosensitive properties of hybrid collagen peptide-polymer
      hydrogels.
AB  - A hybrid hydrogel based on collagen-mimetic peptides has been designed with
      tunable thermosensitive properties. By changing the number of POG repeats within
      the collagen peptide sequence, the thermal stability of the triple helical
      physical crosslinks of a peptide-polymer conjugate can be altered, thus tuning
      the stiffness of the hydrogel as a function of temperature. This report focuses
      on three different thermally responsive collagen peptide, PEG-based hydrogels and
      validates their use as stimuli-responsive materials. 

PMID- 24926621
TI  - Life Cycle Assessment for desalination: a review on methodology feasibility and
      reliability.
AB  - As concerns of natural resource depletion and environmental degradation caused by
      desalination increase, research studies of the environmental sustainability of
      desalination are growing in importance. Life Cycle Assessment (LCA) is an ISO
      standardized method and is widely applied to evaluate the environmental
      performance of desalination. This study reviews more than 30 desalination LCA
      studies since 2000s and identifies two major issues in need of improvement. The
      first is feasibility, covering three elements that support the implementation of
      the LCA to desalination, including accounting methods, supporting databases, and
      life cycle impact assessment approaches. The second is reliability, addressing
      three essential aspects that drive uncertainty in results, including the
      incompleteness of the system boundary, the unrepresentativeness of the database,
      and the omission of uncertainty analysis. This work can serve as a preliminary
      LCA reference for desalination specialists, but will also strengthen LCA as an
      effective method to evaluate the environment footprint of desalination
      alternatives. 

PMID- 24926622
TI  - Differentiating enteric Escherichia coli from environmental bacteria through the
      putative glucosyltransferase gene (ycjM).
AB  - This study is to tackle the challenge posed by the "naturalized" Escherichia coli
      population against the worldwide practice of E. coli-based water quality
      monitoring. In the literature, the putative glucosyltransferase gene (ycjM) of E.
      coli has been identified in silico to be one of the 114 genes specific to enteric
      E. coli. Based on the sequence of E. coli K-12 MG1655, a PCR assay (ycjPCR)
      targeting ycjM was developed in this study. As demonstrated by the ycjPCR assay
      using 367 E. coli strains isolated from animal feces, 97.2% of the isolates
      carried the ycjM with variations from 93.9% to 100% among nine different host
      sources, but none of the 17 strains of non-E. coli bacteria and only 23.0% of the
      environment-isolated cryptic Escherichia strains contained the ycjM. These data
      experimentally confirmed ycjM to be enteric specific. Our study also showed that
      the ycjPCR assay was superior to the commonly used tuf- or uidA-based PCR methods
      in differentiating enteric E. coli from beta-D-glucuronidase-positive
      environmental bacteria. Furthermore, study on 190 E. coli isolates from water
      samples, using EPA Method 1603 followed by bacterial identification with Biolog
      MicroStationTM and ycjPCR assay, indicated that the prevalence of ycjM in the E.
      coli water isolates had a significant (p < 0.05, odds ratio ) spatial variation
      from 69.6% to 93.8%. These data suggest that E. coli profile using EPA Method
      1603 or other beta-D-glucuronidase-activity-based methods may need further
      analysis using the ycjM profile to accurately determinate fecal pollution in
      water.

PMID- 24926623
TI  - Current diagnosis and management of achalasia.
AB  - Achalasia is the best characterized primary esophageal motility disorder of the
      esophagus and typically presents with absent peristalsis of the esophageal body
      and a failure of the lower esophageal sphincter to relax upon swallowing on
      manometry, associated with progressively severe dysphagia, regurgitation,
      aspiration, chest pain, and weight loss. The diagnosis is suggested by barium
      swallow and endoscopy, and confirmed by manometry. As there is no curative
      treatment for achalasia, treatment is confined to disruption of the lower
      esophageal sphincter to improve bolus passage. Treatment modalities available for
      this purpose include pneumatic dilation, laparoscopic Heller myotomy and since
      recently peroral endoscopic myotomy or POEM. In this review, we will discuss the
      current diagnosis, management, and treatment options of achalasia.

PMID- 24926624
TI  - Radiofrequency ablation in the treatment of large hepatic hemangiomas: a
      comparison of multitined and internally cooled electrodes.
AB  - OBJECTIVE: Radiofrequency (RF) ablation is an accepted nonsurgical treatment of
      hepatic hemangiomas, but with an appreciable complication rate. Our study aimed
      to assess the safety and efficacy of RF ablation, administered with either
      multitined expandable electrodes or with internally cooled cluster electrodes, in
      the treatment of large (>=10 cm diameter) hepatic hemangiomas. METHODS: We
      retrospectively reviewed our sequential experience of treating 43 large hepatic
      hemangiomas in 42 patients with RF ablation/multitined expandable electrodes or
      with RF ablation/internally cooled electrodes. Twenty-two hemangiomas in 21
      patients were treated with expandable electrode (multitined electrode group), and
      21 hemangiomas in 21 patients were treated with internally cooled cluster
      electrode (internally cooled electrode group). RESULTS: Among the 43 large
      hepatic hemangiomas, 27 subcapsular lesions were treated by a laparoscopic
      approach, and 16 lesions located in liver parenchyma were treated by a computed
      tomography-guided percutaneous approach. In the multitined electrode group, RF
      ablation treatment was performed in all 21 patients in 1 session. In the
      internally cooled electrode group, 18 patients were treated by RF ablation in 1
      session, and 3 patients, with >=14.0-cm single hemangioma, were treated with RF
      ablation in 2 sessions. Complete ablation was achieved in 81.8% (18/22) and 90.5%
      (19/21) in the multitined electrode group and the internally cooled electrode
      group, respectively (P>0.05). Ablation time for single hemangioma was shorter
      with the internally cooled electrode than with the multitined electrode (P<0.05).
      There were 79 complications related to ablation (2 major and 77 minor) in 31
      patients. All 21 patients in the multitined electrode group experienced
      complications, compared with 10 of 21 patients (47.6%) in the internally cooled
      electrode group (P<0.05). Both of the 2 major complications occurred in the
      multitined electrode group. All the complications were treated successfully with
      conservative measures. CONCLUSIONS: RF ablation is a safe and effective treatment
      for large hepatic hemangiomas. Use of the internally cooled cluster electrodes
      and a more defensive treatment algorithm can reduce the complications.

PMID- 24926625
TI  - Neural mechanisms of mental fatigue.
AB  - Fatigue is defined as a decline in the ability and efficiency of mental and/or
      physical activities that is caused by excessive mental and/or physical
      activities. Fatigue can be classified as physical or mental. Mental fatigue
      manifests as potentially impaired cognitive function and is one of the most
      significant causes of accidents in modern society. Recently, it has been shown
      that the neural mechanisms of mental fatigue related to cognitive task
      performance are more complex than previously thought and that mental fatigue is
      not caused only by impaired activity in task-related brain regions. There is
      accumulating evidence supporting the existence of mental facilitation and
      inhibition systems. These systems are involved in the neural mechanisms of mental
      fatigue, modulating the activity of task-related brain regions to regulate
      cognitive task performance. In this review, we propose a new conceptual model:
      the dual regulation system of mental fatigue. This model contributes to our
      understanding of the neural mechanisms of mental fatigue and the regulatory
      mechanisms of cognitive task performance in the presence of mental fatigue.

PMID- 24926626
TI  - Quantification of polyclonal free light chains in clinical samples using a single
      turbidimetric immunoassay.
AB  - BACKGROUND: Elevated polyclonal serum free light chain (FLC) levels have been
      associated with increased mortality and disease activity in many conditions.
      Currently, polyclonal FLC quantification requires summation of individual
      FLCkappa and FLClambda assays. Here we present a single assay for combined FLC
      (cFLC, Combylite) which reduces assay time and eliminates potential imprecision
      errors incurred by summating FLC assays (SigmaFLC). METHODS: Sheep FLCkappa- and
      FLClambda-specific antibodies were conjugated to latex microparticles to quantify
      FLCkappa and FLClambda in a single assay. Combylite results were compared to
      SigmaFLC (Freelite) in 132 healthy controls and 1127 patient samples. The utility
      of cFLC for predicting all-cause mortality in a haematological referral
      population was evaluated. RESULTS: cFLC and SigmaFLC results were highly
      concordant (Passing-Bablok equation y=0.98x-1.59 mg/L, R2=0.96). Combylite assay
      imprecision was low at concentrations around the upper normal range [coefficient
      of variation (CV) 5.5%, 54 mg/L] and the upper limit of the measuring range (CV
      5.5%, 170 mg/L). cFLC levels were significantly raised in disease states compared
      with healthy controls. Additionally, cFLC >65 mg/L was associated with shorter
      overall survival in a haematological referral population (hazard ratio=4.5,
      p<0.001). CONCLUSIONS: cFLC values obtained using Combylite were comparable to
      SigmaFLC results over a wide concentration range, were elevated in diseases
      characterised by B cell activation and were associated with increased mortality
      in a haematological referral population. These observations indicate the
      Combylite assay has value for investigating the role of B cell activation in
      disparate disease groups and could be considered as a surrogate indication of B
      cell function.

PMID- 24926627
TI  - Response to Jacobs: N Latex FLC serum free light-chain assays in patients with
      renal impairment.

PMID- 24926628
TI  - Hypoglycemic effect of Rhizophora mucronata in streptozotocin induced diabetic
      rats.
AB  - Rhizophora mucronata, plant of Mangroove family, found on the coastal region of
      India and used in treatment of various diseases. Different parts of plants are
      used in treatment of diabetes as folkloric medicine. The present study was
      designed to evaluate the hypoglycemic effect of hydro-alcoholic extract of R.
      mucronata. Streptozotocin (STZ)-induced diabetic rats were treated with RME (100
      mg/kg and 200 mg/kg) and glibenclamide (0.5 mg/kg). Blood glucose levels were
      evaluated for the acute and sub-acute studies and body weight of rats were also
      monitored. All the treatments showed the highly significant (p<0.01) hypoglycemic
      effect in both the acute and the sub-acute studies. RME and glibenclamide treated
      rats were maintained the body weight during the study period while as the body
      weight of diabetic rats had gone down. The result of this study scientifically
      proved the hypoglycemic folkloric use of leaves of R. mucronata in treatment of
      diabetes.

PMID- 24926629
TI  - A randomised controlled trial of the effects of Brain Wave Vibration training on
      mood and well-being.
AB  - BACKGROUND: The goal was to investigate the effects of Brain Wave Vibration
      (BWV), a meditation practised in a class involving rhythmic movements of the
      head, neck and body practised with related yoga-style exercises, and to isolate
      the rhythmic effects. METHODS: A randomised controlled trial was conducted with
      assessments pre- and post-trial and immediately before and after each session.
      Thirty-one healthy adults were assessed for mood, sleep, mindfulness, health and
      well-being, and pre- and post-class activation-deactivation. Participants were
      randomly assigned to either BWV in toto or a control group having similar yoga
      exercises without the rhythmic components. Participants completed eight to twelve
      75-min classes of BWV or control training over 8-12 weeks. To control for
      expectation participants were told only that the aim was to compare two subtly
      different styles of Korean yoga. RESULTS: The BWV group had comparatively greater
      improvements in sleep duration and efficiency, although they had higher baseline
      inefficiency, and post-trial they had better global sleep and well-being and
      fewer illness symptoms, and better tiredness and energy post-class. Both groups
      benefitted in mood, mindfulness and vitality post-trial with improved tension and
      calmness post-class. CONCLUSIONS: The participants of both interventions had
      better mood and well-being on the whole following the trial and were more relaxed
      immediately after a class. However, BWV training was unique in its benefits to
      sleep, health, well-being, energy and tiredness, warranting further research.

PMID- 24926630
TI  - [Pharmacology of Raynaud's phenomenon].
AB  - Raynaud's phenomenon (RP) is characterised by transient ischaemia in the
      extremities in response to cold or emotions. It can be primary (idiopathic) or
      secondary to an underlying disease. The pathophysiology of RP is multifactorial
      and complex. Microvascular impairment is a hallmark of the disease. The objective
      of this work is to review the different pharmacological treatments currently used
      in the management of RP, from their mechanism of action to the available evidence
      regarding their efficacy. We also propose to discuss potential pharmacological
      targets such as the potentiation of the nitric oxide pathway, or the inhibition
      of the RhoA-Rho kinase pathway. The last part of this review deals with drug
      induced RP. Among various medications, beta-blockers, interferons, tyrosine
      kinase inhibitors or cytotoxic agents such as bleomycin are involved. 

PMID- 24926631
TI  - [Doxycycline or how to create new with the old?].
AB  - Tetracyclines are broad-spectrum antibiotics that interfere with protein
      synthesis. They were first widely prescribed by dermatologists in the early 1950s
      in the treatment of acne. More recently, their biological actions on
      inflammation, proteolysis, angiogenesis, apoptosis, metal chelation,
      ionophoresis, and bone metabolism were studied. Matrix metalloproteinases (MMPs)
      are a family of proteolytic enzymes that degrade components of the extracellular
      matrix (ECM). MMPs have direct or indirect effects on the vascular endothelium
      and the vascular relaxation/contraction system. The therapeutic effects of
      tetracyclines and analogues were studied in rosacea, bullous dermatoses,
      neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms,
      cancer metastasis, periodontitis and autoimmune diseases autoimmune diseases such
      as rheumatoid arthritis and scleroderma. In addition, downregulation of MMP using
      doxycycline could be beneficial in reducing vascular dysfunction mediated by MMPs
      and progressive damage of the vascular wall. We review the nonantibiotic
      properties of doxycycline and its potential clinical applications. 

PMID- 24926632
TI  - [Baclofen and liver cirrhosis: literature review and safety precautions
      implemented within the system CAMTEA].
AB  - The off-label prescribing of high dose baclofen (HDB) has been recently spreading
      in France. The impact of HDB on subjects with liver cirrhosis remains poorly
      known. The main pharmacodynamic and pharmacokinetic data on baclofen result from
      studies on healthy subjects or using low doses of treatment. The specific
      biodisponibility and elimination of HDB have not been studied yet in cirrhosis.
      National pharmacovigilance reports suggest that a careful use of baclofen or even
      HDB could be possible in compensated cirrhosis. However, theoretical risks of
      baclofen overdose exist in cases of hepatorenal syndrome or portosystemic shunt.
      Baclofen could also induce a specific pharmacological potentiation of hepatic
      encephalopathy and gastropathy. Within CAMTEA, a regional team-based
      multidisciplinary system for delivering and monitoring off-label medications in
      alcohol use disorders, a set of predefined precautions for using baclofen in
      cirrhosis have been implemented, until further information becomes available.
      These precautions notably consist of a protocolized process for declaring adverse
      events, and a hepatologic follow-up associated with the usual multidisciplinary
      care system set up within CAMTEA. 

PMID- 24926633
TI  - [Use of Nadis((r)) software to improve adverse drug reaction reporting of
      antiretroviral drugs: experience in south west of France (midi-pyrenees)].
AB  - OBJECTIVES: To study the value of the module of pharmacovigilance in Nadis(r) to
      improve the antiretroviral (ARV) drugs-induced adverse drug reactions (ADRs)
      reporting. METHODS: We collected the ADRs reported for 17 months from November
      2010 until April 2012. Following data were recorded: characteristics of patients,
      ADRs, ARV drugs. The number of ADRs was compared to those collected in the same
      period (17 months) before use of Nadis(r). RESULTS: The 119 ADRs reported (an
      increase of 183%) for 109 patients ADRs were mainly gastrointestinal (21.8%)
      followed by renal (20.2%), neuro-psychiatric (16.8%), hepatic (13.5%), cutaneous
      (8.4%), metabolic (6.7%) and others (12.6%). The repartition of ARV drugs was:
      nucleoside (31.8%), nucleotide (13.6%) reverse transcriptase inhibitors
      respectively, non-nucleoside reverse transcriptase inhibitors (13.1%), protease
      inhibitors (36.4%), and integrase inhibitors (5.1%). CONCLUSION: Our results show
      the improvement of ARV-induced ADRs reporting by Nadis(r) which could be used to
      reduce the rate of under-reporting in patients exposed to these drugs.

PMID- 24926634
TI  - [New frequent adverse reaction of PPI in older adults: mild hyponatremia].
AB  - Hyponatremia is a rare side effect described in the product characteristics of
      proton pump inhibitors (PPIs). Hyponatremia in the elderly (>65 years) was
      assessed in patients with exposure to PPIs for at least one year compared to
      controls not exposed to PPIs counterparts. Included 145 patients, twenty-four
      patients (16.6%) had moderate hyponatremia ([120-134] mEq/L). Forty-eight
      patients (33.1%) were treated with PPIs. In the end, 31.3% [18.7%-46.3%] of the
      treated population for more than a year by PPI suffered moderate hyponatremia
      against only 9.3% [14.3%-16.9%] in the rest of the population, giving an odds
      ratio of 4.4 ([1.8-11.1], p=0.001). The relationship between hyponatremia dose
      was not significant (R2=0.05, p=0.74). By our study, we show that the risk of
      moderate hyponatremia is increased by chronic use of PPI in the elderly
      population. We also specify a notion of prevalence between 18.7% and 46.3%. 

PMID- 24926635
TI  - [Treatment with erlotinib after gefitinib induced hepatotoxicity: literature
      review and case report].
AB  - Gefitinib and erlotinib are selective epidermal growth factor receptor-tyrosine
      kinase (EGFR-TK) inhibitor. They are approved for the treatment of adults with
      locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating
      mutations of EGFR-TK. We report the case of a hepatitis cytolytic during
      gefitinib treatment with a positive rechallenge. A relay by erlotinib has been
      initiated and doesn't give recurrence of hepatotoxicity. From a literature review
      and this observation, arguments have been provided to justify erlotinib as a safe
      and well-tolered alternative for patients who have to stop gefitinib after a
      severe hepatotoxicity. 

PMID- 24926636
TI  - [How people use the internet to find information on medicines?].
AB  - OBJECTIVE: To quantify and characterize the use of the Internet to search for
      information about medicines. METHODS: A random sample of subjects was interviewed
      in the city of Bordeaux (France) in November 2012 regarding their use of the
      Internet to find information on medicines. RESULTS: Among 103 interviewed
      subjects (median age: 38 years; 53.4% of men), 48 (46.6%) reported using the
      Internet to find information about medicines (58.3% of women). Two-thirds (66.7%)
      declared visiting consumer forums. However, nearly 60% reported to first consult
      a health professional. Three subjects had already bought medicines on the web and
      half (52.0%) of those who never made a purchase on the Internet would not trust
      the quality of the medicine. CONCLUSION: Even if purchasing medicines on the web
      remains rare, this media is frequently used to find information on medicines and
      most often on websites of questionable quality.

PMID- 24926637
TI  - Sirolimus-related systemic thrombotic microangiopathy after renal
      transplantation.
AB  - We describe the case of a renal transplant patient who developed de novo biopsy
      proven thrombotic microangiopathy (TMA) and deep venous thrombosis after
      treatment with sirolimus (SRL). We discuss the clinical course, diagnosis and
      therapeutics of this patient in the context of the literature. 

PMID- 24926638
TI  - [Antidepressants and tamoxifen: an unrecognized interaction].
AB  - The interaction between tamoxifen and antidepressants which are CYP2D6 inhibitors
      is unknown, as shown in our study in which these antidepressants are prescribed
      to 11% of women receiving tamoxifen. 

PMID- 24926639
TI  - Imiquimod and pulmonary embolism: a case report.
AB  - Bilateral pulmonary embolism possibly related due to topically applied imiquimod
      is reported in a 47-year-old male patient with no evidence of risk factors. 

PMID- 24926640
TI  - [Necrotizing fasciitis related to injections of morphine (Skenan((r))) in a HIV
      infected patient].
AB  - We report here a case of necrotizing fasciitis occurred because of intravenous
      misuse of morphine sulfate (Skenan ((r))). Several factors are pertinent: the
      type of infection, rare but severe, the double localization of the necrotizing
      fasciitis, complicated by sepsis, the patient profile (HIV-infected) and the
      injected substance (opiate). 

PMID- 24926643
TI  - Novel chemical synthesis and characterization of CeTi(2)O(6) brannerite.
AB  - Cerium titanate CeTi2O6 was prepared by a new soft chemistry route in aqueous
      solution. A suite of characterization techniques, including X-ray diffraction,
      thermal analysis, vibrational spectroscopy, and scanning and transmission
      electron spectroscopy, were employed to investigate the brannerite structure
      formation and its bulk properties. The synthesized powder formed the brannerite
      crystal structure upon calcination at temperatures as low as 800  degrees C.
      Samples sintered at 1350  degrees C possess a high level of crystallinity. X-ray
      absorption near-edge structure results indicate the presence of six-coordinated
      Ce(4+) in the brannerite samples. 

PMID- 24926641
TI  - [Antipsychotics-induced acute necrotizing enterocolitis: a case report].
AB  - The acute necrotizing enterocolitis (ANE) is a partial or total necrosis of the
      small and large intestine. This is a case report of an antipsychotic induced ANE.

PMID- 24926642
TI  - [Bradykinin mediated angioedema with ACE inhibitor in combination with
      immunosupressive agents].
AB  - We present a serious case of bradykinin mediated angioedema with upper airway
      disorders resulting from drug interaction between angiotensin-converting enzyme
      inhibitors and immunosuppressant agents. 

PMID- 24926644
TI  - Fabrication and characterization of ZnO@CdS core-shell nanostructure using
      acetate precursors: XRD, FESEM, DRS, FTIR studies and effects of cadmium ion
      concentration on band gap.
AB  - ZnO@CdS core-shell nano-structure has been synthesized using zinc acetate
      dihydrate, and cadmium acetate dihydrate as simple precursors in a water-ethanol
      matrix without using any surfactant, ligand or chelating agents. The effect of
      different concentrations of cadmium acetate and sodium sulfide on optical and
      electronic properties of ZnO@CdS core-shell was investigated. The morphology and
      structure of the ZnO@CdS core-shell nano-structures have been confirmed by field
      emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD)
      measurements. The results showed that the ZnO@CdS core-shell nano-structure is
      mixed cubic and hexagonal structures. FESEM results showed the mono-dispersed and
      uniform size of 39nm. Optical properties were studied by UV-visible diffuse
      reflectance spectroscopy (DRS) technique and the results showed that band gaps of
      ZnO@CdS core-shell nanocomposites were red shifted by increasing the cadmium
      concentration. FTIR spectrum of ZnO@CdS core-shell nano-structure showed a band
      at 482cm(-1) correlated to ZnO bond and a band at 630cm(-1) due to the stretching
      frequency of CdS bond. 

PMID- 24926645
TI  - Development of a sigDE-based real-time reverse-transcriptase PCR for the
      detection of viable Salmonella enterica.
AB  - Salmonella is the most common cause of bacterial food poisoning in humans
      worldwide. Thus, rapid and reliable methods for the detection of this pathogen
      are required. Real-time reverse-transcriptase polymerase chain reaction (rt-RT
      PCR), which detects the presence of mRNA (shorter half-life than DNA) has shown
      great potential for detecting viable pathogens. We recently identified a few new
      potential specific DNA sequences for Salmonella enterica using a comparative
      genomics method (Chen et al., 2010). In the present study, we examined the
      expression of the Salmonella-specific sigDE operon (encoding invasion proteins
      within the pathogenicity island 5) under typical growth conditions to determine
      whether sigDE could be a useful viability marker for the bacterium. We then
      assayed sigDE mRNA from cells heat-treated at 60 degrees C, 100 degrees C, and
      121 degrees C (autoclaved), and found that mRNA was degraded in autoclaved
      bacterial samples. These results showed that the sigDE transcript is a suitable
      mRNA target for rt-RT-PCR with samples pretreated at 121 degrees C. Thus, an rt
      RT-PCR using sigDE primers was developed for the detection of viable Salmonella.
      An RNA internal amplification control was constructed by overlap extension PCR,
      synthesized using in vitro transcription with a T7 RNA polymerase promoter, and
      incorporated into the rt-RT-PCR system to eliminate false-negative results. The
      rt-RT-PCR system has the capability of specifically detecting all the tested S.
      enterica serovars, and the detection limit of this assay with cultures of
      Salmonella Typhimurium ATCC 13311 was 10(1) colony-forming units (CFU)/mL. After
      18-h enrichment, sigDE-based rt-RT-PCR could detect as low as 10(0) CFU/mL of
      Salmonella from egg broth and milk.

PMID- 24926646
TI  - The guillotine knife: a novel tool for safe endoscopic cutting of intracranial
      membranes.
AB  - This article describes a new endoscopic cutting tool that acts like a guillotine.
      It enables safe cutting of membranes overlying neurovascular structures because
      the footplate protects these structures from inadvertent injury. The footplate is
      introduced under the membrane, elevating it slightly, and then the membrane is
      cut while pushing the blade down into the footplate. The guillotine knife has
      been used in various endoscopic procedures such as septostomies, arachnoid cyst
      fenestrations, colloid cysts resections, and fenestrations of other
      intraventricular membranes. The authors think that the guillotine knife is a
      useful addition to the neuroendoscopic armamentarium. 

PMID- 24926647
TI  - Worse outcomes for patients undergoing brain tumor and cerebrovascular procedures
      following the ACGME resident duty-hour restrictions.
AB  - OBJECT: On July 1, 2003, the Accreditation Council for Graduate Medical Education
      (ACGME) implemented duty-hour restrictions for resident physicians due to
      concerns for patient and resident safety. Though duty-hour restrictions have
      increased resident quality of life, studies have shown mixed results with respect
      to patient outcomes. In this study, the authors have evaluated the effect of duty
      hour restrictions on morbidity, mortality, length of stay, and charges in
      patients who underwent brain tumor and cerebrovascular procedures. METHODS: The
      Nationwide Inpatient Sample was used to evaluate the effect of duty-hour
      restrictions on complications, mortality, length of stay, and charges by
      comparing the pre-reform (2000-2002) and post-reform (2005-2008) periods.
      Outcomes were compared between nonteaching and teaching hospitals using a
      difference-in-differences (DID) method. RESULTS: A total of 90,648 patients were
      included in the analysis. The overall complication rate was 11.7%, with the rates
      not significantly differing between the pre- and post-duty hour eras (p = 0.26).
      Examination of hospital teaching status revealed that complication rates
      decreased in nonteaching hospitals (12.1% vs 10.4%, p = 0.0004) and remained
      stable in teaching institutions (11.8% vs 11.9%, p = 0.73) in the post-reform
      era. Multivariate analysis demonstrated a significantly higher complication risk
      in teaching institutions (OR 1.33 [95% CI 1.11-1.59], p = 0.0022), with no
      significant change in nonteaching hospitals (OR 1.11 [95% CI 0.91-1.37], p =
      0.31). A DID analysis to compare the magnitude in change between teaching and
      nonteaching institutions revealed that teaching hospitals had a significantly
      greater increase in complications during the post-reform era than nonteaching
      hospitals (p = 0.040). The overall mortality rate was 3.0%, with a significant
      decrease occurring in the post-reform era in both nonteaching (5.0% vs 3.2%, p <
      0.0001) and teaching (3.2% vs 2.3%, p < 0.0001) hospitals. DID analysis to
      compare the changes in mortality between groups did not reveal a significant
      difference (p = 0.40). The mean length of stay for all patients was 8.7 days,
      with hospital stay decreasing from 9.2 days to 8.3 days in the post-reform era (p
      < 0.0001). The DID analysis revealed a greater length of stay decrease in
      nonteaching hospitals than teaching institutions, which approached significance
      (p = 0.055). Patient charges significantly increased in the post-reform era for
      all patients, increasing from $70,900 to $96,100 (p < 0.0001). The DID analysis
      did not reveal a significant difference between the changes in charges between
      teaching and nonteaching hospitals (p = 0.17). CONCLUSIONS: The implementation of
      duty-hour restrictions correlated with an increased risk of postoperative
      complications for patients undergoing brain tumor and cerebrovascular
      neurosurgical procedures. Duty-hour reform may therefore be associated with worse
      patient outcomes, contrary to its intended purpose. Due to the critical condition
      of many neurosurgical patients, this patient population is most sensitive and
      likely to be negatively affected by proposed future increased restrictions.

PMID- 24926648
TI  - Endoscopic approach to colloid cyst: what is the optimal entry point and
      trajectory?
AB  - OBJECTIVES: An optimal entry point and trajectory for endoscopic colloid cyst
      (ECC) resection helps to protect important neurovascular structures. There is a
      large discrepancy in the entry point and trajectory in the neuroendoscopic
      literature. METHODS: Trajectory views from MRI or CT scans used for cranial image
      guidance in 39 patients who had undergone ECC resection between July 2004 and
      July 2010 were retrospectively evaluated. A target point of the colloid cyst was
      extended out to the scalp through a trajectory carefully observed in a 3D model
      to ensure that important anatomical structures were not violated. The relation of
      the entry point to the midline and coronal sutures was established. Entry point
      and trajectory were correlated with the ventricular size. RESULTS: The optimal
      entry point was situated 42.3 +/- 11.7 mm away from the sagittal suture, ranging
      from 19.1 to 66.9 mm (median 41.4 mm) and 46.9 +/- 5.7 mm anterior to the coronal
      suture, ranging from 36.4 to 60.5 mm (median 45.9 mm). The distance from the
      entry point to the target on the colloid cyst varied from 56.5 to 78.0 mm, with a
      mean value of 67.9 +/- 4.8 mm (median 68.5 mm). Approximately 90% of the optimal
      entry points are located 40-60 mm in front of the coronal suture, whereas their
      perpendicular distance from the midline ranges from 19.1 to 66.9 mm. The location
      of the "ideal" entry points changes laterally from the midline as the ventricles
      change in size. CONCLUSIONS: The results suggest that the optimal entry for ECC
      excision be located at 42.3 +/- 11.7 mm perpendicular to the midline, and 46.9 +/
      5.7 mm anterior to the coronal suture, but also that this point differs with the
      size of the ventricles. Intraoperative stereotactic navigation should be
      considered for all ECC procedures whenever it is available. The entry point
      should be estimated from the patient's own preoperative imaging studies if
      intraoperative neuronavigation is not available. An estimated entry point of 4 cm
      perpendicular to the midline and 4.5 cm anterior to the coronal suture is an
      acceptable alternative that can be used in patients with ventriculomegaly.

PMID- 24926649
TI  - A reduction in errors is associated with prospectively recording them.
AB  - OBJECT: Error recording and monitoring is an important component of error
      prevention and quality assurance in the health sector given the huge impact of
      medical errors on the well-being of patients and the financial loss incurred by
      health institutions. With this in mind, assessing the effect of reporting errors
      should be a cause worth pursuing. The object in this study was to examine the
      null hypothesis that recording and publishing errors do not affect error patterns
      in a clinical practice. METHODS: Intraoperative errors and their characteristics
      were prospectively recorded between May 2000 and May 2013 in the neurosurgical
      practice of the senior author (M.B.). The error pattern observed between May 2000
      and August 2006, which has been previously described (Group A), was compared with
      the error pattern observed between September 2006 and May 2013 (Group B).
      RESULTS: A total of 1108 cases in Group A and 974 cases in Group B were
      surgically treated. A total of 2684 errors were recorded in Group A, while 1892
      errors were recorded in Group B. The ratios of cranial to spinal procedures
      performed in Groups A and B were 3:1 and 10:1, respectively, while the ratios of
      general to local anesthesia in the two groups were 2:1 and 1.3:1, respectively (p
      < 0.0001 for both). There was a significantly decreased proportion of cases with
      error (87% to 83%, p < 0.006), mean errors per case (2.4 to 1.9, p < 0.0001),
      proportion of error-related complications (16.7% to 5.5%, p < 0.002), and
      clinical impacts of error (2.7% to 1.0%, p < 0.0001) in Group B compared with
      Group A. Errors in Group B tended to be more preventable than those in Group A
      (85.8% vs 78.5%, p < 0.0001). A significant reduction was also noticed with most
      types of error. A descending trend in the mean errors per case was demonstrated
      from the years 2001 to 2012; however, an increased severity of errors (22.6% to
      29.5%, p < 0.0001) was recorded in Group B compared with Group A. CONCLUSIONS:
      Data in this study showed that the act of recording errors might alter behaviors,
      resulting in fewer errors.

PMID- 24926650
TI  - Descriptive epidemiology of pituitary tumors in the United States, 2004-2009.
AB  - OBJECT: Pituitary tumors are abnormal growths that develop in the pituitary
      gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains
      the largest aggregation of population-based data on the incidence of primary CNS
      tumors in the US. These data were used to determine the incidence of tumors of
      the pituitary and associated trends between 2004 and 2009. METHODS: Using
      incidence data from 49 population-based state cancer registries, 2004-2009, age
      adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3
      (International Classification of Diseases for Oncology, Third Edition) histology
      codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300,
      8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by
      patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual
      percent change (APC) scores and 95% confidence intervals were also calculated
      using Joinpoint to characterize trends in incidence rates over time. Diagnostic
      confirmation by subregion of the US was also examined. The overall annual
      incidence rate increased from 2.52 (95% CI 2.46-2.58) in 2004 to 3.13 (95% CI
      3.07-3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%
      5.61%). When stratifying by patient sex, the annual incidence rate increased from
      2.42 (95% CI 2.33-2.50) to 2.94 (95% CI 2.85-3.03) in men and 2.70 (95% CI 2.62
      2.79) to 3.40 (95% CI 3.31-3.49) in women, with APCs of 4.35% (95% CI 3.21%
      5.51%) and 4.34% (95% CI 2.23%-6.49%), respectively. When stratifying by race,
      the annual incidence rate increased from 2.31 (95% CI 2.25-2.37) to 2.81 (95% CI
      2.74-2.88) in whites, 3.99 (95% CI 3.77-4.23) to 5.31 (95% CI 5.06-5.56) in
      blacks, 1.77 (95% CI 1.26-2.42) to 2.52 (95% CI 1.96-3.19) in American Indians or
      Alaska Natives, and 1.86 (95% CI 1.62-2.13) to 2.03 (95% CI 1.80-2.28) in Asians
      or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%-4.95%), 5.25% (95% CI
      3.19%-7.36%), 5.31% (95% CI -0.11% to 11.03%), and 2.40% (95% CI -3.20% to
      8.31%), respectively. When stratifying by Hispanic ethnicity, the annual
      incidence rate increased from 2.46 (95% CI 2.40-2.52) to 3.03 (95% CI 2.97-3.10)
      in non-Hispanics and 3.12 (95% CI 2.91-3.34) to 4.01 (95% CI 3.80-4.24) in
      Hispanics, with APCs of 4.15% (95% CI 2.67%-5.65%) and 5.01% (95% CI 4.42%
      5.60%), respectively. When stratifying by age at diagnosis, the incidence of
      pituitary tumor was highest for those 65-74 years old and lowest for those 15-24
      years old, with corresponding overall age-adjusted incidence rates of 6.39 (95%
      CI 6.24-6.54) and 1.56 (95% CI 1.51-1.61), respectively. CONCLUSIONS: In this
      large patient cohort, the incidence of pituitary tumors reported between 2004 and
      2009 was found to increase. Possible explanations for this increase include
      changes in documentation, changes in the diagnosis and registration of these
      tumors, improved diagnostics, improved data collection, increased awareness of
      pituitary diseases among physicians and the public, longer life expectancies,
      and/or an actual increase in the incidence of these tumors in the US population.

PMID- 24926651
TI  - Carotid cutdown for surgical retrieval of a guidewire introducer: an unusual
      complication after mitral valve repair.
AB  - With the use of endovascular techniques and indwelling catheters, potential
      complications can include embolization of fragments or components of various
      systems. The authors describe the surgical retrieval of a guidewire introducer
      from the right common carotid artery (CCA). A 64-year-old man was found to have a
      foreign body within the right CCA on CT angiography after he had presented with a
      transient ischemic attack. He had undergone a complex mitral valve repair several
      months before presenting to the authors' facility. That procedure involved a
      femoral artery cutdown and the insertion of an endovascular aortic balloon for
      cardiac bypass. As in most endovascular procedures, guidewire introducers were
      probably used to facilitate the introduction of the guidewire into the system
      during the procedure. Although rare, iatrogenic embolization of the introducer
      probably occurred during use of the guidewire. The guidewire introducer was
      successfully retrieved without complication by using a standard carotid cutdown
      approach. It is extraordinarily unusual for an extracorporeal part of an
      implantable system to embolize to the carotid circulation. To the authors'
      knowledge, this is the only reported case of an embolized guidewire introducer
      and the use of a carotid exposure to retrieve an intraluminal foreign body. This
      case demonstrates that a carotid cutdown approach can be used successfully for
      the retrieval of intraluminal extracranial carotid artery foreign bodies. 

PMID- 24926652
TI  - From Pergamon to Army Base Hospital No. 5: the history and significance of the
      galea aponeurotica in the evolution of neurosurgery.
AB  - The authors trace the etymology and historical significance of galea or
      epicranial aponeurosis. In ancient Greece, galea referred to a helmet worn by
      soldiers, typically made of animal hide or leather. Throughout antiquity,
      physicians referred to all soft tissue between the skin and the skull as
      panniculus, a standard established by Galen of Pergamon. A manual of surgery in
      the Middle Ages referred to the entire scalp as a "great panicle that is called
      pericranium." During the early Renaissance, Leonardo da Vinci famously and
      stylistically analogized the dissection of the cranium with the peeling of an
      onion. Not until 1724 would the tendinous sheath connecting the frontalis and
      occipitalis muscles be defined as "Galea tendinosa cranii." By 1741, the
      convention of referring to the galea as an aponeurosis was well established.
      Harvey Cushing's wartime experiences at Army Base Hospital No. 5 reinforced the
      surgical significance of the galea. Operative mortality was significantly
      diminished due to "closure of the wounds with buried sutures in the galea." This
      operative nuance was then passed from teacher to pupil and has now become one of
      the tenets of modern neurosurgical practice. 

PMID- 24926653
TI  - Stereotactic radiosurgery for sylvian fissure arteriovenous malformations with
      emphasis on hemorrhage risks and seizure outcomes.
AB  - OBJECT: Sylvian fissure arteriovenous malformations (AVMs) present substantial
      management challenges because of the critical adjacent blood vessels and
      functional brain. The authors investigated the outcomes, especially hemorrhage
      and seizure activity, after stereotactic radiosurgery (SRS) of AVMs within or
      adjacent to the sylvian fissure. METHODS: This retrospective single-institution
      analysis examined the authors' experiences with Gamma Knife surgery for AVMs of
      the sylvian fissure in cases treated from 1987 through 2009. During this time, 87
      patients underwent SRS for AVMs in the region of the sylvian fissure. Before
      undergoing SRS, 40 (46%) of these patients had experienced hemorrhage and 36
      (41%) had had seizures. The median target volume of the AVM was 3.85 cm(3) (range
      0.1-17.7 cm(3)), and the median marginal dose of radiation was 20 Gy (range 13-25
      Gy). RESULTS: Over a median follow-up period of 64 months (range 3-275 months),
      AVM obliteration was confirmed by MRI or angiography for 43 patients. The
      actuarial rates of confirmation of total obliteration were 35% at 3 years, 60% at
      4 and 5 years, and 76% at 10 years. Of the 36 patients who had experienced
      seizures before SRS, 19 (53%) achieved outcomes of Engel class I after treatment.
      The rate of seizure improvement was 29% at 3 years, 36% at 5 years, 50% at 10
      years, and 60% at 15 years. No seizures developed after SRS in patients who had
      been seizure free before treatment. The actuarial rate of AVM hemorrhage after
      SRS was 5% at 1, 5, and 10 years. This rate equated to an annual hemorrhage rate
      during the latency interval of 1%; no hemorrhages occurred after confirmed
      obliteration. No permanent neurological deficits developed as an adverse effect
      of radiation; however, delayed cyst formation occurred in 3 patients.
      CONCLUSIONS: Stereotactic radiosurgery was an effective treatment for AVMs within
      the region of the sylvian fissure, particularly for smaller-volume AVMs. After
      SRS, a low rate of hemorrhage and improved seizure control were also evident.

PMID- 24926654
TI  - Jugulotympanic paragangliomas treated with Gamma Knife radiosurgery: a single
      center review of 58 cases.
AB  - OBJECT: Jugulotympanic paragangliomas (JTPs) are rare benign tumors whose
      surgical treatment is usually associated with partial resection of the lesion,
      high morbidity, and even death. Gamma Knife radiosurgery (GKRS) has been reported
      as a useful treatment option. The goal of this retrospective study is to analyze
      the role of GKRS in tumor volume control and clinical outcomes of these patients.
      METHODS: A total of 75 patients with JTPs were treated with GKRS at the authors'
      center from 1995 to 2012. The authors analyzed those treated during this period
      to allow for a minimal observation time of 2 years. The MR images and clinical
      reports of these patients were reviewed to assess clinical and volumetric
      outcomes of the tumors. The radiological and clinical assessments, along with a
      group of prognostic factors measured, were analyzed using descriptive methods.
      The time to volumetric and clinical progression was analyzed using the Kaplan
      Meier method. Prognostic factors were identified using log-rank statistics and
      multivariate Cox regression models. RESULTS: The mean follow-up was 86.4 months.
      The authors observed volumetric tumor control in 94.8% of cases. In 67.2% of
      cases, tumor volume decreased by a mean of 40.1% from the original size. Of
      patients with previous tinnitus, 54% reported complete recovery. Improvement of
      other symptoms was observed in 34.5% of cases. Overall, clinical control was
      achieved in 91.4% of cases. Previous embolization and familial history of
      paraganglioma were selected as significant prognostic factors for volumetric
      response to GKRS treatment in the univariate analysis. In multivariate analysis,
      no factors were significantly correlated with progression-free survival. No
      patient died of side effects related to GKRS treatment or tumor progression.
      CONCLUSIONS: Gamma Knife radiosurgery is an effective, safe, and efficient
      therapeutic option for the treatment of these tumors as a first-line treatment or
      in conjunction with traditional surgery, endovascular treatment, or conventional
      fractionated radiotherapy.

PMID- 24926655
TI  - Vessel perforation during withdrawal of Trevo ProVue stent retriever during
      mechanical thrombectomy for acute ischemic stroke.
AB  - The authors report a case of an intracranial extravasation during the withdrawal
      of a Trevo ProVue stent retriever device in a patient being treated for acute
      ischemic stroke. An 82-year-old woman developed sudden left hemiparesis and
      aphasia during an urgent cardiac catheterization procedure for a non-ST elevation
      myocardial infarction. She had a baseline National Institutes of Health Stroke
      Scale (NIHSS) score of at least 10 and no improvement with intravenous
      administration of tissue plasminogen activator (tPA). Cerebral angiography was
      performed with conscious sedation, confirming an occlusion of the superior
      division of the right middle cerebral artery (MCA). Using standard technique, a
      Trevo thrombectomy device was deployed across the clot. Post-thrombectomy control
      angiography demonstrated complete revascularization of the right MCA. The device
      was then gently withdrawn without difficulty. Immediately afterward the patient's
      blood pressure showed a sudden and significant elevation. Immediate posttreatment
      angiography demonstrated active extravasation from the posterior wall of the
      communicating segment of the right internal carotid artery. Rapid cessation of
      bleeding was achieved with intravenous administration of protamine and induced
      hypotension. Immediate neurological assessment was performed, which showed motor
      improvement. An immediate postintervention CT scan confirmed a moderate-sized
      subarachnoid hemorrhage and contrast in the prepontine cistern. The patient was
      discharged home on postoperative Day 3 with an NIHSS score of zero. At 6-month
      follow-up in the neurointerventional clinic, her NIHSS and modified Rankin Scale
      scores were both zero. Endovascular stent retriever devices are increasingly
      being used as first-line thrombectomy devices in acute embolic strokes. A unique
      and previously undescribed complication is vessel perforation during withdrawal
      of a stent retriever. Conservative treatment options and reversal of
      anticoagulation should be the first line of treatment for such complications. In
      the authors' case, performing the procedure without anesthesia was helpful in
      assessing the patient's neurological status. 

PMID- 24926658
TI  - Developing an Adaptive Treatment Strategy for Peer-Related Social Skills for
      Children With Autism Spectrum Disorders.
AB  - The purpose of this study was to understand the trajectories of children's
      response to an intervention prior to the end of the treatment in order to inform
      adaptive treatment models for future studies. Participants with autism spectrum
      disorder (ASD) were drawn from a randomized controlled trial comparing 2
      different social skills interventions at children's schools. We excluded children
      with ASD who entered the study with at least 80% time engaged (the average time
      of neurotypical children in the same classes) in order to examine only those who
      were engaged below the typical developing peers' average percentage of time
      engaged. The final sample included 92 children with ASD (82% male, average age =
      8.14 years, average IQ = 89.6). We explored whether playground engagement scores
      measured at entry and midpoint of treatment predicted their engagement scores at
      end of treatment using the Classification and Regression Tree (CART) method.
      Using the CART approach, 4 meaningful subgroups based on children's playground
      engagement scores measured at entry and changes from entry to midpoint were
      identified. These data suggest that measurements of children's behavior midstudy
      can be used to predict children's treatment outcomes. Such data may be used to
      inform decisions to augment or alter programming prior to treatment end in order
      to tailor intervention to best meet the needs of individual children.

PMID- 24926659
TI  - Alternation of flavonoid accumulation under drought stress in Arabidopsis
      thaliana.
AB  - Plants have developed mechanisms to protect themselves against both biotic and
      abiotic environmental stress. Specialized/secondary metabolism is one of the
      stress response mechanisms. Recently, we reported that flavonoids, a class of
      specialized metabolites, including flavonols and anthocyanins with strong radical
      scavenging activity contributed to the mitigation of oxidative and drought stress
      in Arabidopsis thaliana (Arabidopsis). However, the behavior of flavonoids during
      drought stress is still not well-documented. Herein we investigated the time
      series alternation of flavonoids in the aerial part of Arabidopsis (wild type,
      Col-0) during drought stress by LC-QTOF-MS. The drastic alternation of 5
      flavonols and 5 anthocyanins was revealed together with changes in marker
      metabolites of drought stress, e.g., proline, raffinose, and galactinol. These
      findings indicate that flavonols and anthocyanins can mitigate drought stress.

PMID- 24926657
TI  - Comparative transcriptome analysis of four prymnesiophyte algae.
AB  - Genomic studies of bacteria, archaea and viruses have provided insights into the
      microbial world by unveiling potential functional capabilities and molecular
      pathways. However, the rate of discovery has been slower among microbial
      eukaryotes, whose genomes are larger and more complex. Transcriptomic approaches
      provide a cost-effective alternative for examining genetic potential and
      physiological responses of microbial eukaryotes to environmental stimuli. In this
      study, we generated and compared the transcriptomes of four globally-distributed,
      bloom-forming prymnesiophyte algae: Prymnesium parvum, Chrysochromulina
      brevifilum, Chrysochromulina ericina and Phaeocystis antarctica. Our results
      revealed that the four transcriptomes possess a set of core genes that are
      similar in number and shared across all four organisms. The functional
      classifications of these core genes using the euKaryotic Orthologous Genes (KOG)
      database were also similar among the four study organisms. More broadly, when the
      frequencies of different cellular and physiological functions were compared with
      other protists, the species clustered by both phylogeny and nutritional modes.
      Thus, these clustering patterns provide insight into genomic factors relating to
      both evolutionary relationships as well as trophic ecology. This paper provides a
      novel comparative analysis of the transcriptomes of ecologically important and
      closely related prymnesiophyte protists and advances an emerging field of study
      that uses transcriptomics to reveal ecology and function in protists. 

PMID- 24926660
TI  - Association of admission serum calcium levels and in-hospital mortality in
      patients with acute ST-elevated myocardial infarction: an eight-year, single
      center study in China.
AB  - OBJECTIVE: The relationship between admission serum calcium levels and in
      hospital mortality in patients with acute ST-segment elevation myocardial
      infarction (STEMI) has not been well definitively explored. The objective was to
      assess the predictive value of serum calcium levels on in-hospital mortality in
      STEMI patients. METHODS: From 2003 to 2010, 1431 consecutive STEMI patients
      admitted to the First Affiliated Hospital of Nanjing Medical University were
      enrolled in the present study. Patients were stratified according to quartiles of
      serum calcium from the blood samples collected in the emergency room after
      admission. Between the aforementioned groups,the baseline characteristics, in
      hospital management, and in-hospital mortality were analyzed. The association of
      serum calcium level with in-hospital mortality was calculated by a multivariable
      Cox regression analysis. RESULTS: Among 1431 included patients, 79% were male and
      the median age was 65 years (range, 55-74). Patients in the lower quartiles of
      serum calcium, as compared to the upper quartiles of serum calcium, were older,
      had more cardiovascular risk factors, lower rate of emergency
      revascularization,and higher in-hospital mortality. According to univariate Cox
      proportional analysis, patients with lower serum calcium level (hazard ratio
      0.267, 95% confidence interval 0.164-0.433, p<0.001) was associated with higher
      in-hospital mortality. The result of multivariable Cox proportional hazard
      regression analyses showed that the Killip's class>=3 (HR = 2.192, p = 0.026),
      aspartate aminotransferase (HR = 1.001, p<0.001), neutrophil count (HR = 1.123,
      p<0.001), serum calcium level (HR = 0.255, p = 0.001), and emergency
      revascularization (HR = 0.122, p<0.001) were significantly and independently
      associated with in-hospital mortality in STEMI patients. CONCLUSIONS: Serum
      calcium was an independent predictor for in-hospital mortality in patients with
      STEMI. This widely available serum biochemical index may be incorporated into the
      current established risk stratification model of STEMI patients. Further studies
      are required to determine the actual mechanism and whether patients with
      hypocalcaemia could benefit from calcium supplement.

PMID- 24926661
TI  - Overexpression of nuclear apoptosis-inducing factor 1 altered the proteomic
      profile of human gastric cancer cell MKN45 and induced cell cycle arrest at G1/S
      phase.
AB  - Nuclear apoptosis-inducing factor 1 (NAIF1) was previously reported to induce
      apoptosis. Moreover, the expression of NAIF1 was significantly down-regulated in
      human gastric cancer tissues compared to adjacent normal tissues. However, the
      mechanism by which the NAIF1 gene induces apoptosis is not fully understood. Our
      results show that NAIF1 was minimally expressed in all the tested gastric cancer
      cell lines. Our data also demonstrates that NAIF1 is localized in the nuclei of
      cells as detected by monitoring the green fluorescence of NAIF1-GFP fusion
      protein using fluorescent confocal microscopy. Next, a comparative proteomic
      approach was used to identify the differential expression of proteins between
      gastric cancer cell lines MKN45/NAIF1 (-) and MKN45/NAIF1 (+). We found five
      proteins (proteasome 26S subunit 2, proteasome 26S subunit 13, NADH dehydrogenase
      Fe-S protein 1, chaperonin containing TCP1 subunit 3 and thioredoxin reductase 1)
      that were up-regulated and three proteins (ribonuclease inhibitor 1, 14-3-3
      protein epsilon isoform and apolipoprotein A-I binding protein) that were down
      regulated in the MKN45 cells overexpressing NAIF1. We also discovered that NAIF1
      could induce cell cycle arrest at G1/S phase by altering the expression of cell
      cycle proteins cyclinD1, cdc2 and p21. The differentially expressed proteins
      identified here are related to various cellular programs involving cell cycle,
      apoptosis, and signal transduction regulation and suggest that NAIF1 may be a
      tumor suppressor in gastric cancer. Our research provides evidence that
      elucidates the role of how NAIF1 functions in gastric cancer. 

PMID- 24926662
TI  - lnCeDB: database of human long noncoding RNA acting as competing endogenous RNA.
AB  - Long noncoding RNA (lncRNA) influences post-transcriptional regulation by
      interfering with the microRNA (miRNA) pathways, acting as competing endogenous
      RNA (ceRNA). These lncRNAs have miRNA responsive elements (MRE) in them, and
      control endogenous miRNAs available for binding with their target mRNAs, thus
      reducing the repression of these mRNAs. lnCeDB provides a database of human
      lncRNAs (from GENCODE 19 version) that can potentially act as ceRNAs. The
      putative mRNA targets of human miRNAs and the targets mapped to AGO clipped
      regions are collected from TargetScan and StarBase respectively. The lncRNA
      targets of human miRNAs (up to GENCODE 11) are downloaded from miRCode database.
      miRNA targets on the rest of the GENCODE 19 lncRNAs are predicted by our
      algorithm for finding seed-matched target sites. These putative miRNA-lncRNA
      interactions are mapped to the Ago interacting regions within lncRNAs. To find
      out the likelihood of an lncRNA-mRNA pair for actually being ceRNA we take
      recourse to two methods. First, a ceRNA score is calculated from the ratio of the
      number of shared MREs between the pair with the total number of MREs of the
      individual candidate gene. Second, the P-value for each ceRNA pair is determined
      by hypergeometric test using the number of shared miRNAs between the ceRNA pair
      against the number of miRNAs interacting with the individual RNAs. Typically, in
      a pair of RNAs being targeted by common miRNA(s), there should be a correlation
      of expression so that the increase in level of one ceRNA results in the increased
      level of the other ceRNA. Near-equimolar concentration of the competing RNAs is
      associated with more profound ceRNA effect. In lnCeDB one can not only browse for
      lncRNA-mRNA pairs having common targeting miRNAs, but also compare the expression
      of the pair in 22 human tissues to estimate the chances of the pair for actually
      being ceRNAs. AVAILABILITY: Downloadable freely from http://gyanxet
      beta.com/lncedb/.

PMID- 24926663
TI  - Low birth weight male guinea pig offspring display increased visceral adiposity
      in early adulthood.
AB  - Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR)
      predisposes individuals to adult visceral obesity. We postulated that low birth
      weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a
      visceral adipose lipogenic molecular signature involving altered gene expression,
      phosphorylation status of proteins of the lipid synthesis pathway and microRNA
      (miR) expression profile, occurring in association with increased visceral
      adiposity. Normal birth weight (NBW) and LBW (obtained by uterine artery
      ablation) male guinea pig pups were fed a control diet from weaning to 145 days
      and sacrificed. Despite being lighter at birth, LBW pups displayed body weights
      similar to NBW offspring at 145 days. At this age, which represents young
      adulthood, the relative weights of LBW epididymal white adipose tissue (EWAT) and
      lipid content were increased; which was consistent with adipocyte hypertrophy in
      the LBW offspring. Additionally, the mRNA expression of lipid synthesis-related
      genes including acetyl-CoA carboxylase 1 (ACC1), diglyceride acyltransferase 2
      (DGAT2) and peroxisome proliferator-activated receptor gamma 1 (PPARgamma1), was
      increased in LBW EWAT. Further, LBW EWAT displayed decreased phospho-ACC (Ser79)
      and phospho-PPARgamma (Ser273) proteins. Moreover, the mRNA expression of hormone
      sensitive lipase (HSL) and fatty acid binding protein 4 (FABP4), both involved in
      promoting adipose lipid storage, was increased in LBW EWAT. Finally, miR-24 and
      miR-103-2, miRs related to adipocyte development, were both increased in LBW
      EWAT. These findings indicate that, following an adverse in utero environment,
      lipid synthesis-related genes and miR expression, along with phosphorylation
      status of key regulators of lipid synthesis, appear to be chronically altered and
      occur in association with increased visceral adiposity in young adult IUGR male
      offspring. 

PMID- 24926664
TI  - Whole exome sequencing identifies new causative mutations in Tunisian families
      with non-syndromic deafness.
AB  - Identification of the causative mutations in patients affected by autosomal
      recessive non syndromic deafness (DFNB forms), is demanding due to genetic
      heterogeneity. After the exclusion of GJB2 mutations and other mutations
      previously reported in Tunisian deaf patients, we performed whole exome
      sequencing in patients affected with severe to profound deafness, from four
      unrelated consanguineous Tunisian families. Four biallelic non previously
      reported mutations were identified in three different genes: a nonsense mutation,
      c.208C>T (p.R70X), in LRTOMT, a missense mutation, c.5417T>C (p.L1806P), in
      MYO15A and two splice site mutations, c.7395+3G>A, and c.2260+2T>A, in MYO15A and
      TMC1 respectively. We thereby provide evidence that whole exome sequencing is a
      powerful, cost-effective screening tool to identify mutations causing recessive
      deafness in consanguineous families. 

PMID- 24926666
TI  - Molecular characterisation, evolution and expression of hypoxia-inducible factor
      in Aurelia sp.1.
AB  - The maintenance of physiological oxygen homeostasis is mediated by hypoxia
      inducible factor (HIF), a key transcriptional factor of the PHD-HIF system in all
      metazoans. However, the molecular evolutionary origin of this central
      physiological regulatory system is not well characterized. As the earliest
      eumetazoans, Cnidarians can be served as an interesting model for exploring the
      HIF system from an evolutionary perspective. We identified the complete cDNA
      sequence of HIF-1alpha (ASHIF) from the Aurelia sp.1, and the predicted HIF
      1alpha protein (pASHIF) was comprised of 674 amino acids originating from 2,025
      bp nucleotides. A Pairwise comparison revealed that pASHIF not only possessed
      conserved basic helix-loop-helix (bHLH) and Per-Arnt-Sim (PAS) domains but also
      contained the oxygen dependent degradation (ODD) and the C-terminal
      transactivation domains (C-TAD), the key domains for hypoxia regulation. As
      indicated by sequence analysis, the ASHIF gene contains 8 exons interrupted by 7
      introns. Western blot analysis indicated that pASHIF that existed in the polyps
      and medusa of Aurelia. sp.1 was more stable for a hypoxic response than normoxia.

PMID- 24926667
TI  - Health literacy level of Hispanic college students.
AB  - OBJECTIVES: The purpose of this study was to assess the health literacy levels of
      Hispanic college students. METHODS: Participants were students at a major
      Hispanic-serving university in the southwestern United States. The design was
      cross-sectional, and data were collected using the Newest Vital Sign in English.
      Analyses included frequencies and descriptive statistics, simple and multiple
      logistic regression, and chi(2)/Fisher exact tests. RESULTS: A total of 331
      students participated. The overall Newest Vital Sign mean score was 5.1 (standard
      deviation 1.18); more than 90% (n = 299) obtained a score equivalent to an
      "always adequate literacy." A lower percentage than that found by a national
      survey scored at the "below adequate literacy" level. Language spoken at home was
      the only covariate that significantly affected test scores (P = 0.01).
      CONCLUSIONS: The overall health literacy level of the participants was higher
      than the general Hispanic adult population. Investing in the education of
      Hispanics may help to address disparities in health literacy.

PMID- 24926665
TI  - RNA-Seq transcriptome profiling identifies CRISPLD2 as a glucocorticoid
      responsive gene that modulates cytokine function in airway smooth muscle cells.
AB  - Asthma is a chronic inflammatory respiratory disease that affects over 300
      million people worldwide. Glucocorticoids are a mainstay therapy for asthma
      because they exert anti-inflammatory effects in multiple lung tissues, including
      the airway smooth muscle (ASM). However, the mechanism by which glucocorticoids
      suppress inflammation in ASM remains poorly understood. Using RNA-Seq, a high
      throughput sequencing method, we characterized transcriptomic changes in four
      primary human ASM cell lines that were treated with dexamethasone--a potent
      synthetic glucocorticoid (1 uM for 18 hours). Based on a Benjamini-Hochberg
      corrected p-value <0.05, we identified 316 differentially expressed genes,
      including both well known (DUSP1, KLF15, PER1, TSC22D3) and less investigated
      (C7, CCDC69, CRISPLD2) glucocorticoid-responsive genes. CRISPLD2, which encodes a
      secreted protein previously implicated in lung development and endotoxin
      regulation, was found to have SNPs that were moderately associated with inhaled
      corticosteroid resistance and bronchodilator response among asthma patients in
      two previously conducted genome-wide association studies. Quantitative RT-PCR and
      Western blotting showed that dexamethasone treatment significantly increased
      CRISPLD2 mRNA and protein expression in ASM cells. CRISPLD2 expression was also
      induced by the inflammatory cytokine IL1beta, and small interfering RNA-mediated
      knockdown of CRISPLD2 further increased IL1beta-induced expression of IL6 and
      IL8. Our findings offer a comprehensive view of the effect of a glucocorticoid on
      the ASM transcriptome and identify CRISPLD2 as an asthma pharmacogenetics
      candidate gene that regulates anti-inflammatory effects of glucocorticoids in the
      ASM.

PMID- 24926668
TI  - Vitamin D insufficiency/deficiency management.
AB  - OBJECTIVES: In recent years, vitamin D deficiency has been recognized
      increasingly often in patients, and different supplement regimens have been
      prescribed to treat it. There has been no consensus on treatment regimens. This
      study was conducted to determine the management of vitamin D
      deficiency/insufficiency in outpatient adults in northeast Tennessee. METHODS: A
      retrospective record review was conducted in an internal medicine teaching clinic
      for patients seen from July 2007-July 2008 in Johnson City, Tennessee. A total of
      626 nonelectronic charts listed with vitamin D measurements were used in the
      analysis. Data regarding the level of vitamin D, whether treatment was
      prescribed, dose and duration of treatment prescribed, and repeat levels of
      vitamin D, if any were ordered, were collected. Vitamin D deficiency was defined
      as levels <20 ng/mL; vitamin D insufficiency was defined as levels ranging from
      20 to 29.9 ng/mL. RESULTS: Of the 626 patients, 325 (52%) were vitamin D
      deficient or insufficient. Of these 325 patients, 184 were given a low-dose
      supplement and 54 received a high-dose supplement. Eighty-seven were either not
      prescribed any replacement or the dose was unknown (not documented in the chart).
      The mean change in serum vitamin D levels was significantly different for the
      high dose compared with the low dose prescribed. There was no significant sex
      difference in response to the dose given. On average, those who were vitamin D
      deficient experienced a greater change than those who were insufficient and a
      greater change, on average, was observed in those who received a higher dose.
      CONCLUSIONS: Vitamin D deficiency and insufficiency are highly prevalent.
      Clinicians tended to prescribe a high dose of treatment for lower levels of serum
      vitamin D. The response is higher in high-dose treatment. Documentation regarding
      whether vitamin D supplements were given or the dose of supplements was given and
      followed up with repeat levels of vitamin D after treatment was poor.

PMID- 24926669
TI  - Commentary on "vitamin D insufficiency/deficiency management".

PMID- 24926670
TI  - Risk stratification in acute pulmonary embolism: frequency and impact on
      treatment decisions and outcomes.
AB  - OBJECTIVES: Guidelines have recommended that risk stratification be performed in
      patients diagnosed with an acute pulmonary embolism (PE). No study has described
      the use of risk stratification in routine clinical practice. The purpose of this
      study was to measure the frequency and impact of risk stratification on treatment
      decisions and outcomes in patients admitted with acute PE. METHODS: A
      retrospective cohort study was conducted of all of the patients admitted with
      acute PE at two Geisinger community-based teaching hospitals between 2006 and
      2011. Baseline demographics, vital signs, and relevant clinical variables were
      recorded. The Pulmonary Embolism Severity Index was calculated for each patient.
      Risk stratification was defined as the measurement of either a biomarker or an
      echocardiogram within 24 hours of admission. The outcomes measured were short
      term adverse events (in-hospital mortality or need for intensive care) and 30-day
      mortality. RESULTS: The mean age for the study cohort (n = 889) was 61 +/- 17
      years and 52% were men. Overall, 59% of study subjects were risk stratified. The
      frequency of risk stratification did not change over time. Risk stratification
      was associated with assignment to a higher acuity of care and increased use of
      thrombolysis and inferior vena cava filter placement. When controlling for
      severity of illness, risk stratification was a significant predictor of worsened
      short-term adverse outcome (odds ratio 3.43, 95% confidence interval 1.75-6.74, P
      < 0.001) but was not associated with improved 30-day mortality (odds ratio 1.14,
      95% confidence interval 0.66-1.95, P = 0.64). CONCLUSIONS: Risk stratification is
      frequently performed in patients admitted with acute PE and has had a stable
      prevalence during a 5-year period. The use of risk stratification in acute PE is
      associated with assignment to higher levels of care and with more advanced
      treatments. Despite more intense treatment, risk stratification does not improve
      either short-term outcomes or 30-day mortality.

PMID- 24926671
TI  - HSV-1 and HSV-2 seroprevalence in the united states among asymptomatic women
      unaware of any herpes simplex virus infection (Herpevac Trial for Women).
AB  - OBJECTIVES: Recent evidence suggests that the epidemiology of herpes simplex
      viruses (HSVs) is changing because fewer HSV-1 infections are acquired in
      childhood and increased sexual transmission of HSV-1 is reported. The objective
      of the study was to assess the seroprevalence of type-specific antibodies to HSV
      1 and HSV-2 in the United States. METHODS: We used the Western blot antibody
      screening data from a large phase III vaccine efficacy trial (Herpevac Trial for
      Women) to assess the seroprevalence of type-specific antibodies to HSV-1 and HSV
      2 in the United States. RESULTS: The antibody status of 29,022 women (>31,000
      women interviewed and then had their blood drawn for the HSV testing [29,022
      women]) between the ages of 18 and 30 years in the United States revealed that
      increasing age was associated with increasing seroprevalence to HSV. Overall, in
      asymptomatic women unaware of any HSV infection, HSV-1/-2 status was
      positive/negative in 45%, negative/positive in 5%, positive/positive in 7%,
      negative/negative in 38%, and indeterminate in 5%. HSV-1 infections were more
      common in Hispanic and non-Hispanic black women and in the US northeast and in
      individuals living in urban areas. HSV-2 was more common in non-Hispanic black
      women, the US south, and in urban areas. CONCLUSIONS: Seronegative status for
      both HSV-1 and HSV-2 was the second most common finding after positive antibody
      to HSV-1 but negative antibody to HSV-2. Despite recent changes in genital herpes
      epidemiology, most women acquired HSV-1 but not HSV-2 infections before 18 years
      of age. Among participants screened for study participation and who were unaware
      of any HSV infection, progressively higher prevalence of the HSV-1 or HSV-2
      antibody was observed in older subjects. Many women who test positive for HSV-1
      and/or HSV-2 are unaware of their status.

PMID- 24926672
TI  - Commentary on "HSV-1 and HSV-2 seroprevalence in the United States among
      asymptomatic women unaware of any herpes simplex virus infection (Herpevac Trial
      for Women)".

PMID- 24926673
TI  - Access to primary care physicians differs by health insurance coverage in
      Mississippi.
AB  - OBJECTIVES: The objective of the study was to measure how access to primary
      health care in Mississippi varies by type of health insurance. METHODS: We called
      primary care physician (general practitioner, family practice, internal medicine,
      obstetrics/gynecology, and pediatric) offices in Mississippi three times, citing
      different types of health insurance coverage in each call, and asked for a new
      patient appointment with a physician. RESULTS: Of all of the offices contacted,
      7% of offices were not currently accepting new patients who had private
      insurance, 15% of offices were not currently accepting new Medicare patients, 38%
      were not currently accepting new Medicaid patients, and 9% to 21% of office calls
      were unresolved in one telephone call to the office. CONCLUSIONS: Access to
      health insurance does not ensure access to primary health care; access varies by
      type of health insurance coverage.

PMID- 24926674
TI  - Commentary on "Access to primary care physicians differs by health insurance
      coverage in Mississippi".

PMID- 24926675
TI  - Antibody immunodeficiency diseases.
AB  - Among primary immunodeficiencies, antibody deficiencies are the most common.
      Patients often are examined first by multiple medical providers by whom the
      diagnosis may be missed or delayed, because signs and symptoms are usually
      sinopulmonary in origin, simulate common respiratory infections or respiratory
      allergies, and are usually responsive to symptomatic antimicrobial treatment.
      Because these diseases can be treated effectively, it is important to recognize
      them before complications occur. We have provided updated information on the more
      common antibody deficiency syndromes, their diagnostic assessment, and advances
      in treatment.

PMID- 24926676
TI  - Endovascular (intraarterial) treatment of acute ischemic stroke: efficacy not
      supported by clinical trials.
AB  - Intravenous tissue plasminogen activator (IV tPA, alteplase) provides a
      statistically and clinically significant improvement in clinical outcome for
      carefully selected patients with acute ischemic stroke when administered within
      4.5 hours of onset; however, even within the 4.5-hour window, outcome is poor for
      some eligible patients, including those with occlusions of large arteries
      (internal carotid, middle cerebral, and basilar) and many patients do not meet
      the stringent eligibility criteria, especially the time requirement.
      Intraarterial (also known as endovascular or neurointerventional) therapies have
      been developed to address these needs. This review summarizes the current
      evidence for the efficacy of endovascular treatments in acute ischemic stroke.
      Randomized controlled clinical trials of acute ischemic stroke do not show any
      added clinical benefit of endovascular treatment over IV tPA alone in IV tPA
      eligible patients, even in patients with persistent large-artery occlusion, nor
      have these trials provided evidence of clinical benefit in patients ineligible
      for IV tPA because they are >4.5 hours from onset, even if selected by
      sophisticated neuroimaging. The new stent retrievers, however, were rarely used
      in these trials. It remains to be determined from trials with direct head-to-head
      comparisons whether these new devices are superior to standard nonendovascular
      therapy. If there is a role for endovascular treatment of acute ischemic stroke,
      it is for patients who can be treated under 4.5 hours but who are ineligible for
      IV tPA because of increased hemorrhage risk from systemic thrombolytic drug
      effects, although this remains unproven.

PMID- 24926677
TI  - Nitrofurantoin-induced hepatotoxicity: a rare yet serious complication.
AB  - Nitrofurantoin is a commonly prescribed antibiotic for the treatment of recurrent
      uncomplicated urinary tract infections. Its importance has been emphasized by the
      current international clinical practice guidelines for the management of
      uncomplicated cystitis. Since its introduction into clinical practice,
      nitrofurantoin has been associated with various adverse effects, including
      hepatotoxicity. We searched the English-language literature using PubMed and
      SCOPUS for the period 1961 through the end of February 2013. Key search terms
      included "nitrofurantoin AND hepatotoxicity" as well as "nitrofurantoin AND
      hepatitis." When studies or case reports were found, we assessed articles cited
      in those publications. A broad spectrum of liver toxicity associated with
      nitrofurantoin use has been reported, ranging from acute hepatitis, granulomatous
      reaction, cholestasis, or autoimmune-mediated hepatitis to chronic active
      hepatitis that could lead to cirrhosis or death. The mechanism of hepatotoxicity
      is poorly understood, but it is believed to be the result of an immunologic
      process or a direct cytotoxic reaction. It has been postulated that prolonged
      exposure to nitrofurantoin, female sex, advanced age, and reduced renal function
      increase the risk of developing hepatotoxicity. For the management of severe
      cases, corticosteroids have been used along with nitrofurantoin discontinuation.
      Because of mixed results, the utility of corticosteroids has not been proven and
      should be used judiciously. Given the severity and seriousness of the adverse
      effect of hepatotoxicity, clinicians should weigh the risks and benefits of
      nitrofurantoin before initiating therapy, especially in long-term prophylaxis in
      high-risk patients. Clinicians also should be well versed in recognizing and
      managing liver injury associated with nitrofurantoin.

PMID- 24926678
TI  - Sports concussions and traumatic brain injury.

PMID- 24926679
TI  - Sports concussion management: part I.
AB  - Concussion is a popular clinical topic that has been the subject of unprecedented
      recent media coverage. As concerns about the potential short- and long-term
      implications of repetitive head injury in sports such as football continue to
      mount, the proper clinical management of concussion seems to increase in
      importance. The days of ignoring the "ding" on the sideline are definitely over.
      A series of updated clinical evaluation and management recommendations from
      international experts are highlighted in this review. The clinical presentation
      of an acute concussion, both the typical and more subtle variations, may be
      evaluated with new validated sideline evaluation tools (eg, Sports Concussion
      Assessment Tool 2). In addition, the role of computerized neuropsychological and
      balance testing in the acute and ongoing evaluation are discussed, along with how
      they contribute to the return-to-play decision. Same-day return to play is
      outdated, and the relative insensitivity of current neuroimaging modalities to
      demonstrate structural damage is highlighted. New therapeutic interventions such
      as amantadine and cognitive rest may improve recovery time. The appropriate
      management of concussion typically results in a normal functional and
      neurocognitive outcome. The recommendations in this article may guide clinicians,
      with varying degrees of prior experience managing concussion, to increase the
      likelihood of an excellent outcome.

PMID- 24926680
TI  - Sports Concussion Management: part II.
AB  - Millions of concussions occur every year in the United States. The public
      interest in concussion has increased after a number of high-profile deaths in
      high school athletes from sports-related head trauma and in some professional
      athletes from chronic traumatic encephalopathy. One of the most active areas of
      research in sports medicine during the last decade has been the evaluation and
      management of concussion. In this second article of a two-part series, we provide
      an overview of the latest scientific advances in concussion research. This
      overview includes an update on the pathobiological changes that occur during
      concussion and the results of biomechanical studies. In addition, to aid the
      practicing clinician, we review the literature on proven and currently studied
      concussion risk factors, including a history of concussion, fatigue, and age.
      Genetic polymorphisms and biomarkers may provide risk-prediction capability, but
      at present the research remains inconclusive. Diffusion tensor imaging and
      functional magnetic resonance imaging are promising technologies that reveal more
      sophisticated data about the impact of concussion on the brain. We review the
      existing literature on the application of these neuroimaging modalities to sports
      concussion. An update from the Fourth International Conference on Concussion in
      Sport, with highlights of new recommendations, and the presentation of the third
      edition of the Sports Concussion Assessment Tool to evaluate acute concussion,
      concludes our review.

PMID- 24926681
TI  - Commentary on "Sports concussion management: parts I and II".

PMID- 24926683
TI  - Perivascular adipose tissue inhibits endothelial function of rat aortas via
      caveolin-1.
AB  - Perivascular adipose tissue (PVAT)-derived factors have been proposed to play an
      important role in the pathogenesis of atherosclerosis. Caveolin-1 (Cav-1),
      occupying the calcium/calmodulin binding site of endothelial NO synthase (eNOS)
      and then inhibiting nitric oxide (NO) production, is also involved in the
      development of atherosclerosis. Thus, we investigated whether PVAT regulated
      vascular tone via Cav-1 and/or endothelial NO pathways. Isometric tension studies
      were carried out in isolated thoracic aortas from Wistar rats in the presence and
      absence of PVAT. Concentration-response curves of phenylephrine, acetylcholine,
      and sodium nitroprusside were illustrated to examine the vascular reactivity and
      endothelial function. The protein expressions of eNOS and Cav-1 were also
      examined in aortic homogenates. Our results demonstrated that PVAT significantly
      enhanced vasoconstriction and inhibited vasodilatation via endothelium-dependent
      mechanism. The aortic NO production was diminished after PVAT treatment, whereas
      protein expression and activity of eNOS were not significantly affected. In
      addition, Cav-1 protein expression was significantly increased in aortas with
      PVAT transfer. Furthermore, a caveolae depleter methyl-beta-cyclodextrin
      abolished the effect of PVAT on the enhancement of vasoconstriction, and reversed
      the impairment of aortic NO production. In conclusion, unknown factor(s) released
      from PVAT may inhibit endothelial NO production and induce vasocontraction via an
      increase of Cav-1 protein expression. 

PMID- 24926684
TI  - Certain adenylated non-coding RNAs, including 5' leader sequences of primary
      microRNA transcripts, accumulate in mouse cells following depletion of the RNA
      helicase MTR4.
AB  - RNA surveillance plays an important role in posttranscriptional regulation.
      Seminal work in this field has largely focused on yeast as a model system,
      whereas exploration of RNA surveillance in mammals is only recently begun. The
      increased transcriptional complexity of mammalian systems provides a wider array
      of targets for RNA surveillance, and, while many questions remain unanswered,
      emerging data suggest the nuclear RNA surveillance machinery exhibits increased
      complexity as well. We have used a small interfering RNA in mouse N2A cells to
      target the homolog of a yeast protein that functions in RNA surveillance (Mtr4p).
      We used high-throughput sequencing of polyadenylated RNAs (PA-seq) to quantify
      the effects of the mMtr4 knockdown (KD) on RNA surveillance. We demonstrate that
      overall abundance of polyadenylated protein coding mRNAs is not affected, but
      several targets of RNA surveillance predicted from work in yeast accumulate as
      adenylated RNAs in the mMtr4KD. microRNAs are an added layer of transcriptional
      complexity not found in yeast. After Drosha cleavage separates the pre-miRNA from
      the microRNA's primary transcript, the byproducts of that transcript are
      generally thought to be degraded. We have identified the 5' leading segments of
      pri-miRNAs as novel targets of mMtr4 dependent RNA surveillance. 

PMID- 24926686
TI  - Differential expression of granulopoiesis related genes in neutrophil subsets
      distinguished by membrane expression of CD177.
AB  - OBJECTIVE: Differential gene expression in CD177+ and CD177- neutrophils was
      investigated, in order to detect possible differences in neutrophil function
      which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV).
      METHODS: Neutrophils were isolated from healthy controls (HC) with high, negative
      or bimodal CD177 expression, and sorted into CD177+ and CD177- subpopulations.
      Total RNA was screened for expression of 24,000 probes with Illumina Ref-8
      Beadchips. Genes showing differential expression between CD177+ and CD177-
      subsets in microarray analysis were re-assessed using quantitative-PCR. CD177
      expression on neutrophil precursors in bone marrow was analyzed using
      quantitative PCR and flowcytometry. RESULTS: The proportion of CD177+ cells
      increased during neutrophil maturation in bone marrow. Fold change analysis of
      gene expression profile of sorted CD177+ and CD177- neutrophils resulted in 14
      genes with fold change (fc) >3 difference in expression. Interestingly, 10 of
      these genes have been reported to change significantly in expression during
      neutrophil maturation, and most of these genes were granule protein (GP) coding
      genes. mRNA expression levels measured by RT-PCR of a number of these GP, and of
      PR3 and MPO were higher in the CD177- neutrophil subset in HC, however,
      particular granule protein amounts were comparable between CD177+ and CD177-
      neutrophil subsets. AAV patients had higher amounts of CD177+ neutrophils, but
      contrary to neutrophils from HC expression of GP-genes was increased, possibly
      due to activation. CONCLUSION: The neutrophil population can be distinguished by
      membrane expression of CD177 into subsets that are different in expression of GP
      mRNA but not in GP protein production. GP gene expression is also elevated in AAV
      patients, which is not explained by skewed distribution of CD177+ and CD177-
      subsets but may be associated with neutrophil activation during on-going
      inflammation.

PMID- 24926685
TI  - Peroxisome proliferator-activated receptor alpha activation induces hepatic
      steatosis, suggesting an adverse effect.
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic
      triglyceride accumulation, ranging from steatosis to steatohepatitis and
      cirrhosis. NAFLD is a risk factor for cardiovascular diseases and is associated
      with metabolic syndrome. Antihyperlipidemic drugs are recommended as part of the
      treatment for NAFLD patients. Although fibrates activate peroxisome proliferator
      activated receptor alpha (PPARalpha), leading to the reduction of serum
      triglyceride levels, the effects of these drugs on NAFLD remain controversial.
      Clinical studies have reported that PPARalpha activation does not improve hepatic
      steatosis. In the present study, we focused on exploring the effect and mechanism
      of PPARalpha activation on hepatic triglyceride accumulation and hepatic
      steatosis. Male C57BL/6J mice, Pparalpha-null mice and HepG2 cells were treated
      with fenofibrate, one of the most commonly used fibrate drugs. Both low and high
      doses of fenofibrate were administered. Hepatic steatosis was detected through
      oil red O staining and electron microscopy. Notably, in fenofibrate-treated mice,
      the serum triglyceride levels were reduced and the hepatic triglyceride content
      was increased in a dose-dependent manner. Oil red O staining of liver sections
      demonstrated that fenofibrate-fed mice accumulated abundant neutral lipids.
      Fenofibrate also increased the intracellular triglyceride content in HepG2 cells.
      The expression of sterol regulatory element-binding protein 1c (SREBP-1c) and the
      key genes associated with lipogenesis were increased in fenofibrate-treated mouse
      livers and HepG2 cells in a dose-dependent manner. However, the effect was
      strongly impaired in Pparalpha-null mice treated with fenofibrate. Fenofibrate
      treatment induced mature SREBP-1c expression via the direct binding of PPARalpha
      to the DR1 motif of the SREBP-1c gene. Taken together, these findings indicate
      the molecular mechanism by which PPARalpha activation increases liver
      triglyceride accumulation and suggest an adverse effect of fibrates on the
      pathogenesis of hepatic steatosis. 

PMID- 24926687
TI  - Intestinal parasitic infections among prison inmates and tobacco farm workers in
      Shewa Robit, north-central Ethiopia.
AB  - BACKGROUND: Intestinal parasitic infections (IPIs) particularly soil-transmitted
      helminthiasis (STH) and schistosomiasis are among neglected tropical diseases
      (NTDs) globally. Apart from being associated with anemia, malabsorption and
      retarded cognitive development these diseases are complicating the clinical
      picture of more serious infections like HIV, TB and malaria. Renewed and up-to
      date information on the epidemiology of IPIs in more vulnerable groups such as
      irrigated-farm workers and prisoners would significantly contribute towards
      improving the health condition of such at-risk groups. METHODS: A cross-sectional
      survey was conducted to determine the prevalence of IPIs among prison inmates and
      tobacco farm workers in Shewa-Robit, north-central Ethiopia in November 2008. A
      total of 236 fecal samples were examined microscopically to detect helminths
      and/or protozoa using direct-smear and formol-ether concentration methods.
      RESULTS: Overall, 8 intestinal parasite species have been recovered singly or in
      combinations from 146 (61.8 %) samples. The prevalence in prison population
      (88/121 = 72.7%) was significantly higher than that in tobacco farm (58/115 =
      50.4%). There were no significant differences in the prevalence of IPI by most
      socio-demographics. Except for hookworm there was no significant difference in
      parasite prevalence between different age-groups though the frequency of
      individual parasites slightly varied between the age-groups. Multivariate
      logistic regression analysis showed that inmates were more likely to acquire IPIs
      than tobacco-farm workers (Odds Ratio (OR) = 2.62, 95% confidence interval (CI) =
      1.52-4.5). In addition, participants who did not report past treatment for IPIs
      were more likely to acquire IPIs than participants who self-reported treatment
      for IPIs in the past twelve months (OR = 3.25, 95% CI = 1.75-6.06). All other
      socio-demographics were not significantly associated with IPIs in univariate
      analysis. Entamoeba histolytica/dispar/moshkovskii was the most frequently
      encountered species in both study sites accounting for 48.8 and 51.7 percent of
      the positives in prison and tobacco farm population respectively. Other
      intestinal parasites detected, with slight variation in prevalence in the two
      study areas, were hookworm, Ascaris lumbricoides, Trichuris trichiura,
      Schistosoma mansoni, Strongyloides stercolaris, Hymenolepis nana and Taenia sp.
      35.5 and 33.0 percent of the total positive cases were mixed infections in Shewa
      Robit prison and tobacco farm, respectively. CONCLUSION: The results show that
      IPIs are common health problems in the studied populations.

PMID- 24926688
TI  - Magnetic resonance imaging and computed tomography characteristics of renal cell
      carcinoma associated with Xp11.2 translocation/TFE3 gene fusion.
AB  - PURPOSE: To characterize Xp11.2 translocation renal cell carcinoma (RCC) using
      magnetic resonance imaging (MRI) and computed tomography (CT). METHODS: This
      study retrospectively collected the MRI and CT data of twelve patients with
      Xp11.2 translocation RCC confirmed by pathology. Nine cases underwent dynamic
      contrast-enhanced MRI (DCE-MRI) and 6 cases underwent CT, of which 3 cases
      underwent MRI and CT simultaneously. The MRI and CT findings were analyzed in
      regard to tumor position, size, hemorrhagic, cystic or necrotic components,
      calcification, tumor density, signal intensity and enhancement features. RESULTS:
      The age of the 12 patients ranged from 13 to 46 years (mean age: 23 years). T2WI
      revealed heterogeneous intensity, hyper-intensity, and slight hypo-intensity in 6
      cases, 2 cases, and 1 case, respectively. On DCE-MR images, mild, moderate, and
      marked rim enhancement of the tumor in the corticomedullary phase (CMP) were
      observed in 1, 6, and 2 cases, respectively. The tumor parenchyma showed iso
      attenuation (n = 4) or slight hyper-attenuation (n = 1) compared to the normal
      renal cortex on non-contrast CT images. Imaging findings were suggestive of
      hemorrhage (n = 4) or necrosis (n = 8) in the tumors, and there was evidence of
      calcification in 8 cases by CT (n = 3) and pathology (n = 8). On dynamic contrast
      enhanced CT images, 3 cases and 1 case manifested moderate and strong CMP
      enhancement, respectively. Nine tumors by MRI and 4 tumors by CT showed prolonged
      enhancement. Three neoplasms presented at stage I, 2 at stage II, 3 at stage III,
      and 4 at stage IV according the 2010 AJCC staging criteria. CONCLUSIONS: XP11.2
      translocation RCC should be considered when a child or young adult patient
      presents with a renal tumor with heterogeneous features such as hemorrhage,
      necrosis, cystic changes, and calcification on CT and MRI and/or is accompanied
      by metastatic evidence.

PMID- 24926691
TI  - Phenotype and genotype analysis in patients with macular corneal dystrophy.
AB  - AIM: The aim of this study was to analyse corneal morphological organisation and
      identify mutations in the carbohydrate sulfotransferase 6 gene (CHST6) in
      patients with macular corneal dystrophy originating in a Polish population.
      METHODS: Macular corneal dystrophy was diagnosed in 24 patients based on the slit
      lamp exam, confocal microscopy, 1310 nm time domain and 840 nm spectral domain
      optical coherence tomography. 10 corneal buttons obtained from penetrating
      keratoplasty were processed for light microscopy. Genetic analysis of the CHST6
      gene was performed, followed by a study of the sequencing results. RESULTS:
      Highly reflective, diffuse corneal deposits and a general increase in
      reflectivity were revealed with optical coherence tomography and confocal
      microscopy. The deposits extended from the Bowman layer to the Descemet membrane
      and correlated with the Alcian blue-positive granular-filamentous material into
      and around the stromal keratocytes confirmed by structural analysis of the
      corneal buttons. The genetic analysis of the blood samples identified the
      following mutations and single nucleotide polymorphisms: novel P64L
      (heterozygous), Y110C (homozygous), R162G and L200R, and M1L (heterozygous and
      homozygous). CONCLUSIONS: Genetic mutation heterogeneity was revealed. No
      phenotype heterogeneity was revealed among patients with in vivo corneal
      morphology assessment or histological analysis.

PMID- 24926690
TI  - Differences in muscle transcriptome among pigs phenotypically extreme for fatty
      acid composition.
AB  - BACKGROUND: Besides having an impact on human health, the porcine muscle fatty
      acid profile determines meat quality and taste. The RNA-Seq technologies allowed
      us to explore the pig muscle transcriptome with an unprecedented detail. The aim
      of this study was to identify differentially-expressed genes between two groups
      of 6 sows belonging to an Iberian * Landrace backcross with extreme phenotypes
      according to FA profile. RESULTS: We sequenced the muscle transcriptome acquiring
      787.5 M of 75 bp paired-end reads. About 85.1% of reads were mapped to the
      reference genome. Of the total reads, 79.1% were located in exons, 6.0% in
      introns and 14.9% in intergenic regions, indicating expressed regions not
      annotated in the reference genome. We identified a 34.5% of the intergenic
      regions as interspersed repetitive regions. We predicted a total of 2,372
      putative proteins. Pathway analysis with 131 differentially-expressed genes
      revealed that the most statistically-significant metabolic pathways were related
      with lipid metabolism. Moreover, 18 of the differentially-expressed genes were
      located in genomic regions associated with IMF composition in an independent GWAS
      study in the same genetic background. Thus, our results indicate that the lipid
      metabolism of FAs is differently modulated when the FA composition in muscle
      differs. For instance, a high content of PUFA may reduce FA and glucose uptake
      resulting in an inhibition of the lipogenesis. These results are consistent with
      previous studies of our group analysing the liver and the adipose tissue
      transcriptomes providing a view of each of the main organs involved in lipid
      metabolism. CONCLUSIONS: The results obtained in the muscle transcriptome
      analysis increase the knowledge of the gene regulation of IMF deposition, FA
      profile and meat quality, in terms of taste and nutritional value. Besides, our
      results may be important in terms of human health.

PMID- 24926692
TI  - Smartphone-based hearing screening in noisy environments.
AB  - It is important and recommended to detect hearing loss as soon as possible. If it
      is found early, proper treatment may help improve hearing and reduce the negative
      consequences of hearing loss. In this study, we developed smartphone-based
      hearing screening methods that can ubiquitously test hearing. However,
      environmental noise generally results in the loss of ear sensitivity, which
      causes a hearing threshold shift (HTS). To overcome this limitation in the
      hearing screening location, we developed a correction algorithm to reduce the HTS
      effect. A built-in microphone and headphone were calibrated to provide the
      standard units of measure. The HTSs in the presence of either white or babble
      noise were systematically investigated to determine the mean HTS as a function of
      noise level. When the hearing screening application runs, the smartphone
      automatically measures the environmental noise and provides the HTS value to
      correct the hearing threshold. A comparison to pure tone audiometry shows that
      this hearing screening method in the presence of noise could closely estimate the
      hearing threshold. We expect that the proposed ubiquitous hearing test method
      could be used as a simple hearing screening tool and could alert the user if they
      suffer from hearing loss. 

PMID- 24926693
TI  - Defect profile estimation from magnetic flux leakage signal via efficient
      managing particle swarm optimization.
AB  - In this paper, efficient managing particle swarm optimization (EMPSO) for high
      dimension problem is proposed to estimate defect profile from magnetic flux
      leakage (MFL) signal. In the proposed EMPSO, in order to strengthen exchange of
      information among particles, particle pair model was built. For more efficient
      searching when facing different landscapes of problems, velocity updating scheme
      including three velocity updating models was also proposed. In addition, for more
      chances to search optimum solution out, automatic particle selection for re
      initialization was implemented. The optimization results of six benchmark
      functions show EMPSO performs well when optimizing 100-D problems. The defect
      simulation results demonstrate that the inversing technique based on EMPSO
      outperforms the one based on self-learning particle swarm optimizer (SLPSO), and
      the estimated profiles are still close to the desired profiles with the presence
      of low noise in MFL signal. The results estimated from real MFL signal by EMPSO
      based inversing technique also indicate that the algorithm is capable of
      providing an accurate solution of the defect profile with real signal. Both the
      simulation results and experiment results show the computing time of the EMPSO
      based inversing technique is reduced by 20%-30% than that of the SLPSO-based
      inversing technique. 

PMID- 24926694
TI  - Respiratory monitoring by a field ionization sensor based on Trichel pulses.
AB  - In this paper, a novel method for respiratory monitoring is presented. The method
      is based on Trichel pulses (TPs) using a simple field ionization sensor which
      consists of a needle electrode and a plate electrode. Experiments have been
      conducted to demonstrate that different respiratory patterns, including normal,
      ultra-fast, deep breaths, and apnea could be easily monitored in real time by
      detecting the changes in the TP frequency. The vital capacity could also be
      assessed by calculating the variation of TP frequency. It is found that the
      operation principle of the proposed sensor is based on the effects of breath
      airflow and the atomized water in exhaled air on the TP frequency by changing the
      ionization process and the dynamics of charged particles in the short gap. The
      influences of applied voltage and ambient parameters have also been investigated.

PMID- 24926695
TI  - The use of screen-printed electrodes in a proof of concept electrochemical
      estimation of homocysteine and glutathione in the presence of cysteine using
      catechol.
AB  - Screen printed electrodes were employed in a proof of concept determination of
      homocysteine and glutathione using electrochemically oxidized catechol via a 1,4
      Michael addition reaction in the absence and presence of cysteine, and each
      other. Using cyclic voltammetry, the Michael reaction introduces a new adduct
      peak which is analytically useful in detecting thiols. The proposed procedure
      relies on the different rates of reaction of glutathione and homocysteine with
      oxidized catechol so that at fast voltage scan rates only homocysteine is
      detected in cyclic voltammetry. At slower scan rates, both glutathione and
      homocysteine are detected. The combination of the two sets of data provides
      quantification for homocysteine and glutathione. The presence of cysteine is
      shown not to interfere provided sufficient high concentrations of catechol are
      used. Calibration curves were determined for each homocysteine and glutathione
      detection; where the sensitivities are 0.019 uA . uM(-1) and 0.0019 uA . uM(-1)
      and limit of detections are ca. 1.2 uM and 0.11 uM for homocysteine and
      glutathione, respectively, within the linear range. This work presents results
      with potential and beneficial use in re-useable and/or disposable point-of-use
      sensors for biological and medical applications.

PMID- 24926696
TI  - Using [18F]FBAU for imaging brain tumor progression in an F98/tk-luc glioma
      bearing rat model.
AB  - 1-(2-Deoxy-2-[18F]fluoro-beta-D-arabinofuranosyl)-5-bromouracil ([18F]FBAU), a
      substitute for thymine, has been reported as an effective reporter probe by which
      to trace cellular metabolism with its positron emission. In the present study, a
      rat xenograft model bearing F98 glioma transfected with dual reporter genes,
      herpes simplex virus type 1 thymidine kinase (HSV1-tk) and firefly luciferase
      (luc) was used for monitoring tumor progression by multimodalities of molecular
      imaging using [18F]FBAU and D-luciferase as probes. Rat F98 glioma cells were
      transfected with the pC1-tk-IRES-luc vectors. The selected stable clone was
      renamed as the F98/tk-luc cell line. Fischer 344 male rats bearing orthotropic
      F98/tk-luc gliomas in the left brain were used. On day 13 post tumor inoculation,
      biodistribution, positron emission tomography (PET), magnetic resonance imaging
      (MRI) and ex vivo autoradiography were performed. The surviving fraction of
      F98/tk-luc cells treated with 15 uM ganciclovir (GCV) was 15.9%, and the uptake
      of [131I]FIAU in these cells was significantly enhanced when compared with F98
      cells. The correlation coefficient of tumor volume vs. the bioluminescence in the
      F98/tk-luc glioma-bearing rats was 0.90. The biodistribution showed that the
      accumulation ratios of [18F]FBAU for glioma-to-normal brain were 9.16, 14.24, 5.7
      and 13.7 at 30, 60, 90 and 120 min post i.v. injection, respectively. Consistent
      tumor enhancement of [18F]FBAU/PET imaging was also noted from 30-90 min post
      injection. Ex vivo autoradiography also confirmed significant [18F]FBAU uptake in
      tumors. In conclusion, [18F]FBAU may be used as a PET probe for monitoring glioma
      progression in animal models and may have potential for clinical use as well.

PMID- 24926697
TI  - Congenital cataracts due to a novel 2-bp deletion in CRYBA1/A3.
AB  - Congenital cataracts, which are a clinically and genetically heterogeneous group
      of eye disorders, lead to visual impairment and are a significant cause of
      blindness in childhood. A major proportion of the causative mutations for
      congenital cataracts are found in crystallin genes. In the present study, a novel
      deletion mutation (c.590-591delAG) in exon 6 of CRYBA1/A3 was identified in a
      large family with autosomal dominant congenital cataracts. An increase in local
      hydrophobicity was predicted around the mutation site; however, further studies
      are required to determine the exact effect of the mutation on betaA1/A3
      crystallin structure and function. To the best of our knowledge, this is the
      first report of an association between a frameshift mutation in exon 6 of
      CRYBA1/A3 and congenital cataracts. 

PMID- 24926698
TI  - Fusion of HepG2 cells with mesenchymal stem cells increases cancer-associated and
      malignant properties: an in vivo metastasis model.
AB  - In the present study, we have tested the hypothesis that fusion between an
      altered cell and a mesenchymal stem cell produces a hybrid cell with enhanced
      characteristics associated with metastatic cancer cells, and we have developed a
      flexible model for investigating the mechanisms of metastasis. Human HepG2 cells
      with low metastatic potential were induced to fuse with rat bone marrow
      mesenchymal stem cells, and the progeny were compared with the parental cells for
      possession of enhanced in vitro and in vivo characteristics of malignant cells.
      Compared to the parental cells, the fused cells exhibited enhanced expression of
      E-cadherin, vimentin, Twist, Snail, matrix metalloproteinase 2 and 9 activities,
      aneuploidy and enhanced in vitro invasion and migration. In an in vivo xenograft
      assay, the fused cells generated increased numbers of metastatic liver and lung
      lesions. This model system is a flexible tool for investigation of the mechanisms
      of stem cell fusion in carcinogenesis and metastasis and for the discovery of new
      therapeutic targets to inhibit metastasis.

PMID- 24926699
TI  - What's new in Shock? July 2014.

PMID- 24926700
TI  - Orchestration of transplantation tolerance by regulatory dendritic cell therapy
      or in-situ targeting of dendritic cells.
AB  - PURPOSE OF REVIEW: Extensive research in murine transplant models over the past
      two decades has convincingly demonstrated the ability of regulatory dendritic
      cells (DCregs) to promote long-term allograft survival. We review important
      considerations regarding the source of therapeutic DCregs (donor or recipient)
      and their mode of action, in-situ targeting of DCregs, and optimal therapeutic
      regimens to promote DCreg function. RECENT FINDINGS: Recent studies have defined
      protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient
      origin subvert allogeneic T-cell responses and promote long-term organ transplant
      survival. Particular interest has focused on how donor antigen is acquired,
      processed and presented by autologous dendritic cells, on the stability of
      DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic
      function. New evidence of the therapeutic efficacy of DCregs in a clinically
      relevant nonhuman primate organ transplant model and production of clinical grade
      DCregs support early evaluation of DCreg therapy in human graft recipients.
      SUMMARY: We discuss strategies currently used to promote dendritic cell
      tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells,
      with a view to improved understanding of underlying mechanisms and identification
      of the most promising strategies for therapeutic application.

PMID- 24926702
TI  - Reinventing the health services researcher.

PMID- 24926701
TI  - Homeostatic expansion as a barrier to lymphocyte depletion strategies.
AB  - PURPOSE OF REVIEW: Following lymphodepletion, lymphocytes repopulate the immune
      space both through enhanced thymopoiesis and proliferation of residual
      nondepleted peripheral lymphocytes. The term homeostatic proliferation
      (alternatively homeostatic expansion or lymphopenia-induced proliferation) refers
      to the latter process. Homeostatic proliferation is especially relevant to
      reconstitution of the lymphocyte compartment following immunodepletion therapy in
      transplantation. Repopulating lymphocytes can skew toward an effector memory type
      capable of inducing graft rejection, autoimmunity, or, in the case of allogeneic
      bone marrow transplantation, graft versus host disease. Here we review recent
      studies exploring the biologic mechanisms underlying homeostatic proliferation
      and explore implications for therapy in transplantation. RECENT FINDINGS: Two
      immune-depleting agents, alemtuzumab and rabbit antithymocyte globulin, have been
      well characterized in their abilities to induce an effector-memory phenotype in
      repopulating lymphocytes. Additionally, we have gained new understandings of the
      mechanisms by which the cytokines interleukin-7 and interleukin-15 regulate this
      process. Recent studies have also explored the functions of noncytokine and
      signaling molecules in lymphopenia-induced proliferation. Finally, we have seen
      the promise and limitations of several therapeutic approaches, including
      recombinant interleukin-7 therapy, CD8-targeted antibodies, and peri-transplant
      cyclophosphamide, to treat posttransplant lymphopenia and reduce the risks of
      immune dysregulation following homeostatic proliferation. SUMMARY: Immune
      dysfunction following homeostatic proliferation is a special challenge in
      transplantation. A deeper understanding of the underlying biology has led to a
      number of promising new therapies to overcome this problem.

PMID- 24926703
TI  - Clinical and policy perspectives on the adoption of active surveillance for low
      risk prostate cancer.

PMID- 24926704
TI  - Perceptions of Active Surveillance and Treatment Recommendations for Low-risk
      Prostate Cancer: Results from a National Survey of Radiation Oncologists and
      Urologists.
AB  - BACKGROUND: With the growing concerns about overtreatment in prostate cancer, the
      extent to which radiation oncologists and urologists perceive active surveillance
      (AS) as effective and recommend it to patients are unknown. OBJECTIVE: To assess
      opinions of radiation oncologists and urologists about their perceptions of AS
      and treatment recommendations for low-risk prostate cancer. RESEARCH DESIGN:
      National survey of specialists. PARTICIPANTS: Radiation oncologists and
      urologists practicing in the United States. MEASURES: A total of 1366 respondents
      were asked whether AS was effective and whether it was underused nationally,
      whether their patients were interested in AS, and treatment recommendations for
      low-risk prostate cancer. Pearson's chi test and multivariate logistic regression
      were used to test for differences in physician perceptions on AS and treatment
      recommendations. RESULTS: Overall, 717 (52.5%) of physicians completed the survey
      with minimal differences between specialties (P=0.92). Although most physicians
      reported that AS is effective (71.9%) and underused in the United States (80.0%),
      71.0% stated that their patients were not interested in AS. For low-risk prostate
      cancer, more physicians recommended radical prostatectomy (44.9%) or
      brachytherapy (35.4%); fewer endorsed AS (22.1%). On multivariable analysis,
      urologists were more likely to recommend surgery [odds ratio (OR): 4.19; P<0.001]
      and AS (OR: 2.55; P<0.001), but less likely to recommend brachytherapy (OR: 0.13;
      P<0.001) and external beam radiation therapy (OR: 0.11; P<0.001) compared with
      radiation oncologists. CONCLUSIONS AND RELEVANCE: Most prostate cancer
      specialists in the United States believe AS effective and underused for low-risk
      prostate cancer, yet continue to recommend the primary treatments their
      specialties deliver.

PMID- 24926705
TI  - Development of a pharmacy-based comorbidity index for patients with cancer.
AB  - OBJECTIVE: We aimed to develop and validate a pharmacy-based instrument to
      measure comorbidity among cancer patients. METHODS: Patients diagnosed with
      colorectal, breast, gynecologic, stomach/liver, or renal/bladder cancers were
      identified from the New Zealand Cancer Registry between July 2006 and June 2008
      for a development cohort (n=14096) and from July 2008 to December 2009 for a
      validation cohort (n=11014). Nineteen conditions were identified using community
      pharmaceutical data collected in the year before cancer diagnosis; 10 conditions
      were validated against hospital record data. A pharmacy-based comorbidity index
      (PBCI) was developed with each identified condition weighted according to their
      log hazard ratios from age-adjusted and stage-adjusted Cox regression models with
      noncancer death as the outcome. For each individual the weights were summed to
      give a score. Predictive abilities of PBCI were compared with the Charlson and C3
      (hospitalization-based) comorbidity indices. RESULTS: Kappa coefficients for
      conditions identified in notes review compared with pharmaceutical data ranged
      from 0.83 (diabetes) to 0.26 (anxiety/depression). Correlation coefficients with
      the Charlson ranged from 0.37 to 0.45 across cancers. All comorbidity indices
      were significant predictors of mortality, and differences between models were
      small. The PBCI generally performed as well or better than the Charlson index for
      predicting noncancer death within all cancer sites and slightly outperformed
      other indices in predicting noncancer mortality for breast cancer. CONCLUSIONS:
      The PBCI provides a valid alternative to measuring comorbidity in cancer
      patients. Researchers can use either hospitalization-based or pharmacy-based
      comorbidity measures for risk adjustment purposes.

PMID- 24926706
TI  - Annual patient time costs associated with medical care among cancer survivors in
      the United States.
AB  - BACKGROUND: Although patient time costs are recommended for inclusion in cost
      effectiveness analyses, these data are not routinely collected. We used
      nationally representative data and a medical service-based approach to estimate
      the annual patient time costs among cancer survivors. METHODS: We identified
      adult 6699 cancer survivors and 86,412 individuals without a cancer history ages
      18 years or more from 2008-2011 Medical Expenditure Panel Survey (MEPS). Service
      use was categorized as hospitalizations, emergency room use, provider visits,
      ambulatory surgery, chemotherapy, and radiation therapy. Service time estimates
      were applied to frequencies for each service category and the US median wage rate
      in 2011 was used to value time. We evaluated the association between cancer
      survivorship and service use frequencies and patient time costs with
      multivariable regression models, stratified by age group (18-64 and 65+ y).
      Sensitivity analyses evaluated different approaches for valuing time. RESULTS:
      Cancer survivors were more likely to have hospitalizations, emergency room
      visits, ambulatory surgeries, and provider visits in the past year than
      individuals without a cancer history in adjusted analyses (P<0.05). Annual
      patient time was higher for cancer survivors than individuals without a cancer
      history among those aged 18-64 years (30.2 vs. 13.6 h; P<0.001) and 65+ years
      (55.1 vs. 36.6 h; P<0.001), as were annual patient time costs (18-64 y: $500 vs.
      $226; P<0.001 and 65+ y: $913 vs. $607; P<0.001). CONCLUSIONS: Cancer survivors
      had greater annual medical service use and patient time costs than individuals
      without a cancer history. This medical service-based approach for estimating
      annual time costs can also be applied to other conditions.

PMID- 24926707
TI  - Emergency department crowding predicts admission length-of-stay but not mortality
      in a large health system.
AB  - BACKGROUND: Emergency department (ED) crowding has been identified as a major
      threat to public health. OBJECTIVES: We assessed patient transit times and ED
      system crowding measures based on their associations with outcomes. RESEARCH
      DESIGN: Retrospective cohort study. SUBJECTS: We accessed electronic health
      record data on 136,740 adults with a visit to any of 13 health system EDs from
      January 2008 to December 2010. MEASURES: Patient transit times (waiting,
      evaluation and treatment, boarding) and ED system crowding [nonindex patient
      length-of-stay (LOS) and boarding, bed occupancy] were determined. Outcomes
      included individual inpatient mortality and admission LOS. Covariates included
      demographic characteristics, past comorbidities, severity of illness, arrival
      time, and admission diagnoses. RESULTS: No patient transit time or ED system
      crowding measure predicted increased mortality after control for patient
      characteristics. Index patient boarding time and lower bed occupancy were
      associated with admission LOS (based on nonoverlapping 95% CI vs. the median
      value). As boarding time increased from none to 14 hours, admission LOS increased
      an additional 6 hours. As mean occupancy decreased below the median (80%
      occupancy), admission LOS decreased as much as 9 hours. CONCLUSIONS: Measures
      indicating crowded ED conditions were not predictive of mortality after case-mix
      adjustment. The first half-day of boarding added to admission LOS rather than
      substituted for it. Our findings support the use of boarding time as a measure of
      ED crowding based on robust prediction of admission LOS. Interpretation of
      measures based on other patient ED transit times may be limited to the timeliness
      of care.

PMID- 24926708
TI  - National trends in hospitalizations for sickle cell disease in the United States
      following the FDA approval of hydroxyurea, 1998-2008.
AB  - BACKGROUND: Patients with sickle cell disease (SCD) can suffer frequent hospital
      admissions for painful vasoocclusive crises. Hydroxyurea was approved by the FDA
      in 1998 to decrease the morbidity of SCD, but nationwide hospitalizations for SCD
      in the United States since 1998 have not been evaluated. We hypothesized that the
      availability of hydroxyurea for SCD would be associated with a decrease in
      hospitalizations for SCD over time. OBJECTIVE: To assess trends in
      hospitalization and length-of-stay in hospital for SCD in the United States, 1998
      through 2008. RESEARCH DESIGN: Retrospective cohort study of SCD-related hospital
      discharges in the Nationwide Inpatient Sample of US hospital discharges.
      SUBJECTS: All discharges in the Nationwide Inpatient Sample associated with a
      principal diagnosis of SCD in blacks, 1998 through 2008. MEASURES: Trends in
      hospitalization rates and average length-of-stay in hospital for SCD. RESULTS: We
      found 216 (95% confidence interval, 173.3-258.7) SCD-related hospitalizations per
      100,000 US blacks in 1998 and 178.4 (95% confidence interval, 144.2-212.5) in
      2008, but no consistent yearly decrease, 1998 through 2008 (P=0.30). Conversely,
      the length-of-stay in hospital in 1998 was 5.38 days and in 2008 was 5.18 days,
      an absolute change of 0.2 days and a downward trend that was statistically
      significant. CONCLUSIONS: Between 1998 and 2008, there was not a steady decrease
      in hospitalization rates for the population of SCD in the United States. On the
      contrary, there was a decline in length-of-stay in hospital over this time.
      Hydroxyurea underuse is well documented. Efforts to increase hydroxyurea use may
      help to reduce hospitalization rates.

PMID- 24926709
TI  - Are comparisons of patient experiences across hospitals fair? A study in Veterans
      Health Administration hospitals.
AB  - BACKGROUND: Surveys are increasingly used to assess patient experiences with
      health care. Comparisons of hospital scores based on patient experience surveys
      should be adjusted for patient characteristics that might affect survey results.
      Such characteristics are commonly drawn from patient surveys that collect little,
      if any, clinical information. Consequently some hospitals, especially those
      treating particularly complex patients, have been concerned that standard
      adjustment methods do not adequately reflect the challenges of treating their
      patients. OBJECTIVES: To compare scores for different types of hospitals after
      making adjustments using only survey-reported patient characteristics and using
      more complete clinical and hospital information. RESEARCH DESIGN: We used
      clinical and survey data from a national sample of 1858 veterans hospitalized for
      an initial acute myocardial infarction (AMI) in a Department of Veterans Affairs
      (VA) medical center during fiscal years 2003 and 2004. We used VA administrative
      data to characterize hospitals. The survey asked patients about their experiences
      with hospital care. The clinical data included 14 measures abstracted from
      medical records that are predictive of survival after an AMI. RESULTS:
      Comparisons of scores across hospitals adjusted only for patient-reported health
      status and sociodemographic characteristics were similar to those that also
      adjusted for patient clinical characteristics; the Spearman rank-order
      correlations between the 2 sets of adjusted scores were >0.97 across 9 dimensions
      of inpatient experience. CONCLUSIONS: This study did not support concerns that
      measures of patient care experiences are unfair because commonly used models do
      not adjust adequately for potentially confounding patient clinical
      characteristics.

PMID- 24926710
TI  - Spillover effects of community uninsurance on awareness, treatment, and control
      of hypertension among insured adults.
AB  - BACKGROUND: Although studies have shown that a high rate of uninsurance in a
      community reduces access to and satisfaction with health care among the insured
      population, little is known about whether the community uninsurance rate also
      affects quality of care and clinical outcomes among the insured. OBJECTIVE: To
      assess the spillover effects of the rate of uninsurance in a community on the
      awareness, treatment, and control of hypertension, a chronic condition
      responsible for substantial morbidity and mortality in the United States, among
      insured adults. RESEARCH DESIGN: NHANES III (1988-1994) and the 1999-2010 NHANES
      were linked to data from the Current Population Survey, Area Resource File, and
      InterStudy Competitive Edge. Multivariate probit regression models used 2
      alternative estimation approaches: (1) maximum likelihood estimation, and (2) 2
      stage residual inclusion estimation, an instrumental variables method. MAIN
      OUTCOME MEASURES: Six dichotomous outcomes included: awareness among all subjects
      with hypertension; treatment among all subjects with hypertension and among
      subjects who were aware of their condition; and control among all subjects with
      hypertension, among subjects who were aware of their condition, and among
      subjects receiving treatment. RESULTS: A 10 percentage point increase in the
      community uninsurance rate reduced the probability of receiving antihypertensive
      medications by 4.2 percentage points among insured hypertensive adults and by 5.5
      percentage points among insured hypertensive adults who were aware of their
      hypertension. A 10 percentage point increase in the community uninsurance rate
      also resulted in a 6.8 percentage point decline in the probability of blood
      pressure control among insured hypertensive adults who were aware of their
      condition. CONCLUSIONS: Nationally, the Affordable Care Act is expected to reduce
      the number of uninsured by >30 million by 2016, although changes will be
      experienced by communities to a greater or lesser extent depending on the
      existing numbers and characteristics of the uninsured in the area and the ways in
      which health care reform is implemented. Our results suggest that reductions in
      the community uninsurance rate have the potential to improve quality of care and
      clinical outcomes among the insured.

PMID- 24926711
TI  - Impact of regional clinical pathways on the length of stay in hospital among
      stroke patients in Japan.
AB  - BACKGROUND: Clinical pathways are care plans used by health providers to describe
      essential steps in the care of patients with specific medical conditions.
      Clinical implementation of the regional clinical pathways in Japan has spread,
      and the 2008 fee schedule included a new "regional inter-provider care planning
      fee" for stroke. However, no evidence regarding the efficacy of the regional
      clinical pathways for stroke has appeared. OBJECTIVES: We examined the
      association of regional clinical pathways on the length of in-hospital stay in
      patients with stroke. We also examined whether a variation in the length of in
      hospital stay for stroke patients between hospitals exists, and if so, the impact
      of regional clinical pathways on this variation. RESEARCH DESIGN: Cross-sectional
      analysis using the Diagnosis Procedure Combination database for the period April
      2011 to March of 2012. SUBJECTS: A total of 117,180 patients with the diagnosis
      "cerebral infarction," coded as I63 in ICD10. MEASURES: Associations of the use
      of a regional clinical pathway with the length of in-hospital stay (LOS) were
      estimated by multilevel regression models using a 2-level structure of
      individuals nested within the 1011 hospitals. The models added both patient-level
      factors and hospital-level factors that are potentially associated with LOS.
      RESULTS: Hospitals administering a regional clinical pathway had a significantly
      shorter LOS (9.1 d) than hospitals that did not. Approximately 12% of the
      variation in LOS between hospitals is possibly explained by whether hospitals
      implement regional clinical pathways. Application of regional clinical pathways
      at the individual level is associated with a 7.2-day decrease in LOS at the
      individual level. CONCLUSIONS: These findings suggest that the regional clinical
      pathways are potentially effective in improving the management of stroke patients
      and in promoting the consistency of care between hospitals.

PMID- 24926712
TI  - Trends in family ratings of experience with care and racial disparities among
      Maryland nursing homes.
AB  - BACKGROUND: Providing equitable and patient-centered care is critical to ensuring
      high quality of care. Although racial/ethnic disparities in quality are widely
      reported for nursing facilities, it is unknown whether disparities exist in
      consumer experiences with care and how public reporting of consumer experiences
      affects facility performance and potential racial disparities. METHODS: We
      analyzed trends of consumer ratings publicly reported for Maryland nursing homes
      during 2007-2010, and determined whether racial/ethnic disparities in experiences
      with care changed during this period. Multivariate longitudinal regression models
      controlled for important facility and county characteristics and tested changes
      overall and by facility groups (defined based on concentrations of black
      residents). Consumer ratings were reported for: overall care; recommendation of
      the facility; staff performance; care provided; food and meals; physical
      environment; and autonomy and personal rights. RESULTS: Overall ratings on care
      experience remained relatively high (mean=8.3 on a 1-10 scale) during 2007-2010.
      Ninety percent of survey respondents each year would recommend the facility to
      someone who needs nursing home care. Ratings on individual domains of care
      improved among all nursing homes in Maryland (P<0.01), except for food and meals
      (P=0.827 for trend). However, site-of-care disparities existed in each year for
      overall ratings, recommendation rate, and ratings on all domains of care (P<0.01
      in all cases), with facilities more predominated by black residents having lower
      scores; such disparities persisted over time (P>0.2 for trends in disparities).
      CONCLUSIONS: Although Maryland nursing homes showed maintained or improved
      consumer ratings during the first 4 years of public reporting, gaps persisted
      between facilities with high versus low concentrations of minority residents.

PMID- 24926713
TI  - Trends in childbirth before 39 weeks' gestation without medical indication.
AB  - BACKGROUND: There is increasing attention to labor induction and cesarean
      delivery occurring at 37 0/7-38 6/7 weeks' gestation (early-term) without medical
      indication. OBJECTIVE: To measure prevalence, change over time, patient
      characteristics, and infant outcomes associated with early-term nonindicated
      births. RESEARCH DESIGN AND SUBJECTS: Retrospective analysis using linked
      hospital discharge and birth certificate data for the 7,296,363 uncomplicated
      births (>37 0/7 wk' gestation) between 1995 and 2009 in 3 states. MEASURES: Early
      term nonindicated birth is calculated using diagnosis codes and birth certificate
      records. Secondary outcomes included infant prolonged length of stay and
      respiratory distress. RESULTS: Across uncomplicated term births, the early-term
      nonindicated birth rate was 3.18%. After adjustment, the risk of nonindicated
      birth before 39 0/7 weeks was 86% higher in 2009 than in 1995 [hazard ratio
      (HR)=1.86; 95% confidence interval (CI), 1.81-1.90], peaking in 2006 (HR=2.03;
      P<0.001). Factors independently associated with higher odds included maternal
      age, higher education levels, private health insurance, and delivering at smaller
      volume or nonteaching hospitals. Black women had higher risk of nonindicated
      cesarean birth (HR=1.29; 95% CI, 1.27-1.32), which was associated with greater
      odds of prolonged length of stay [adjusted odds ratio (AOR)=1.60; 95% CI, 1.57
      1.64] and infant respiratory distress (AOR=2.44; 95% CI, 2.37-2.50) compared with
      births after 38 6/7 weeks. Early-term nonindicated induction was also associated
      with comparatively greater odds of prolonged length of stay (AOR=1.20; 95% CI,
      1.17-1.23). CONCLUSIONS: Nearly 4% of all uncomplicated births to term infants
      occurred before 39 0/7 weeks' gestation without medical indication. These births
      were associated with adverse infant outcomes.

PMID- 24926714
TI  - The burden of overweight and obesity on long-term care and Medicaid financing.
AB  - BACKGROUND: The obesity rate among the elderly long-term care (LTC) residents in
      the United States is increasing rapidly. However, there is a paucity of research
      investigating the burden of obesity on LTC and Medicaid financing. The purpose of
      this study is to fill the knowledge gap by estimating the burden of overweight
      and obesity on LTC and Medicaid financing. METHODS: Using nationally
      representative Cost and Use Files of Medicare Current Beneficiary Survey from
      1997 to 2005, we used 2-part model and cohort-based simulation to evaluate the
      effect of overweight and obesity on LTC days and Medicaid expenditures across the
      lifespan among the current elderly population. Combining the per capita estimates
      with 2010 census, we project future aggregate burden of obesity on LTC demand and
      Medicaid cost among baby boomers. RESULTS: Obesity and related chronic diseases
      lead to higher probability to enter LTC facility in a younger age, more LTC days
      before death, and higher lifetime LTC cost reimbursed by Medicaid. However, such
      effect is only statistically significant among women, not significant among men.
      At the population level, we project that overweight and obesity will induce 1.3
      billion or more LTC patient days and $68 billion or more Medicaid costs (in 2012
      value) among baby boomers. CONCLUSIONS: Overweight and obesity among the elderly
      will bring tremendous burden to LTC providers and Medicaid. Policy makers should
      keep the burden of obesity on LTC in mind when planning LTC and Medicaid policy
      reform.

PMID- 24926715
TI  - Privacy-preserving analytic methods for multisite comparative effectiveness and
      patient-centered outcomes research.
AB  - BACKGROUND: For privacy and practical reasons, it is sometimes necessary to
      minimize sharing of individual-level information in multisite studies. However,
      individual-level information is often needed to perform more rigorous statistical
      analysis. OBJECTIVES: To compare empirically 3 analytic methods for multisite
      studies that only require sharing of summary-level information to perform
      statistical analysis that have traditionally required access to detailed
      individual-level data from each site. RESEARCH DESIGN, SUBJECTS, AND MEASURES: We
      analyzed data from a 7-site study of bariatric surgery outcomes within the
      Scalable Partnering Network. We compared the long-term risk of rehospitalization
      between adjustable gastric banding and Roux-en-y gastric bypass procedures using
      a stratified analysis of propensity score (PS)-defined strata, a case-centered
      analysis of risk set data, and a meta-analysis of site-specific effect estimates.
      Their results were compared with the result from a pooled individual-level data
      analysis. RESULTS: The study included 1327 events (18.1%) among 7342 patients.
      The adjusted hazard ratio was 0.71 (95% CI, 0.59, 0.84) comparing adjustable
      gastric banding with Roux-en-y gastric bypass in the individual-level data
      analysis. The corresponding effect estimate was 0.70 (0.59, 0.83) in the PS
      stratified analysis, 0.71 (0.59, 0.84) in the case-centered analysis, and 0.71
      (0.60, 0.84) in both the fixed-effect and random-effects meta-analysis.
      CONCLUSIONS: In this empirical study, PS-stratified analysis, case-centered
      analysis, and meta-analysis produced results that are identical or highly
      comparable with the result from a pooled individual-level data analysis. These
      methods have the potential to be viable analytic alternatives when sharing of
      individual-level information is not feasible or not preferred in multisite
      studies.

PMID- 24926716
TI  - Did HEDIS get it right? Evaluating the quality of a quality measure: adherence to
      beta-blockers and cardiovascular outcomes after myocardial infarction.
AB  - BACKGROUND: As an example of the process that could be used to evaluate and
      optimize the performance of quality measures in routine practice, we evaluated
      whether the Healthcare Effectiveness Data and Information Set (HEDIS) measure
      assessing the "persistence of beta-blocker treatment after a heart attack"
      correlates with post-myocardial infarction (MI) outcomes and whether or not there
      are alternative specifications of this construct which are better predictors
      and/or may be more easily applied. RESEARCH DESIGN: The study included a
      retrospective cohort of 8672 post-MI patients 18 years old and above. We assessed
      the strength of the association between the different adherence measures and the
      composite clinical outcome using multivariable Cox models. We compared the
      predictive capacity of each adherence definition model to one that did not
      contain adherence by computing the change in C-statistics and the continuous net
      reclassification improvement indices (NRIs). RESULTS: Adherence was associated
      with clinical outcome reductions, with hazard ratios ranging from 0.48 (95% CI,
      0.27-0.85) to 0.81 (95% CI, 0.67-0.99). None of the adherence measures, including
      the HEDIS definition, significantly changed the C-statistic relative to a model
      that did not include adherence. However, the short-term adherence measure (having
      72 d covered during the first 90 d postdischarge) showed a large change in NRI
      (correctly reclassifying 12% of cases and 16% of noncases; NRI: 28%; 95% CI, 22%
      38%), although did not significantly differ from the change in NRI with the HEDIS
      measure. CONCLUSIONS: We identified an adherence measure that showed a predictive
      ability as good as that of the HEDIS definition to measure beta-blocker use after
      MI, halving the time of assessment required, and thus, allowing for the
      implementation of quality improvement interventions in a more timely manner.

PMID- 24926717
TI  - Surgical anatomy of the facial nerve relating to facial rejuvenation surgery.
AB  - The aim of this review was to familiarize the reader with critical facial nerve
      anatomy relating to facial rejuvenation surgeries. The temporal branch to the
      upper orbicularis oculi muscle (OOM): The temporal branch was under the
      temporoparietal fascia above the zygomatic arch and divided into 2 to 4 branches.
      The highest level of the twigs that entered the OOM on the x axis and the y axis
      with the origin of the lateral canthus is +2.51 +/- 0.23 cm and +2.70 +/- 0.35
      cm; and the lowest, 0 cm and +2.68 +/- 0.32 cm, respectively. The zygomatic and
      the buccal branch to the lower OOM: All pretarsal and preseptal OOMs were
      innervated by 5 to 7 terminal twigs of the zygomatic branches of the facial nerve
      that approached the muscle at a right angle. The medial portion of the lower OOM
      was innervated by 1 to 2 terminal twigs of the buccal branch, and the middle
      portion was innervated with 2 to 3 twigs of the zygomatic branch. The lateral
      portion was supplied by the uppermost zygomatic branch, which split into 2 to 4
      twigs. The temporal branch to the corrugator supercilii muscle: A plexus mainly
      from the inferior ramus partly from the middle ramus of the temporal branch of
      the facial nerve enters the corrugator supercilii muscle in the supraorbital
      area. The temporal branch has as many as 4 to 7 rami, with interconnection among
      them. The buccal branch to the procerus muscle: The buccal branch crosses the
      intercanthal line (the nasion to the medial canthus) at approximately one third
      laterally. The nerve entrance was within a circle with a diameter of 5 mm, and
      its center was located 9 mm lateral and 10 mm superior from the nasion. It was
      approximately at the midpoint of the lateral half of the intercanthal line and
      the lower one third between the intercanthal line and the tangential line of the
      supraorbital rim. The buccal branch, the buccal fat pad, and the parotid duct:
      The buccal branches and the parotid duct crossed each other within a semicircle
      with a 30-mm radius. The base (diameter) was parallel to a horizontal line
      passing the corner of the mouth and 12 mm above. Its center was located 53 mm
      lateral to it. The buccal branches of the facial nerve have 2 locations at the
      buccal fat pad: type I, branches crossing superficial to the buccal fat pad in 14
      (73.7%) of 19 specimens, and type II, 2 twigs passing through the buccal
      extension of the buccal fat pad in 5 (26.3%) of 19 specimens. The buccal branch
      to the upper orbicularis oris muscle: Approximately 4 branches (4.06 +/- 0.83)
      entering the pars marginalis were found. Most ramifying points (14/17, 82%) were
      located within a circle with a 5-mm radius, and the center was 12 mm lateral and
      26 mm superior to the mouth corner. The mandibular branch according to the neck
      position: At the one-fourth point, the border-nerve distance decreased (4.32 +/-
      2.60 mm) with the neck in ipsilateral rotation and the border-nerve distance
      increased (5.97 +/- 2.62 mm) with the neck in contralateral rotation. We hope
      that this knowledge will aid surgeons in achieving successful outcomes.

PMID- 24926718
TI  - A rare case of an asymptomatic third molar showing a dentigerous cyst with
      ameloblastomatous changes.

PMID- 24926719
TI  - Vocal cord hemangioma: a rare entity.

PMID- 24926720
TI  - Stabilization of premaxilla repositioned during secondary bone grafting in
      complete bilateral cleft lip and palate patients.
AB  - Secondary bone grafting simultaneous to premaxillary repositioning is a well
      recognized surgical procedure for the management of bilateral cleft lip and
      palate patients. Proper stabilization of the repositioned premaxilla is
      considered as a key factor for the success of secondary bone grafting because the
      mobility of the premaxillary segment jeopardizes graft integration. This case
      series reports a reliable method of premaxillary stabilization that incorporated
      the intrasurgical application of resin bone cement to cover and reinforce the
      arch bars or orthodontic brackets applied on the maxillary teeth. Occlusal loads
      were reduced by application of posterior bite blocks on the mandibular teeth. The
      stabilization method was performed on 7 patients (5 women and 2 men) with a mean
      age of 12.4 years. During postsurgery follow-ups, the repositioned premaxillary
      segments did not show mobility in any of the patients. The palatal fistulae were
      completely closed. Panoramic radiographies taken 2 months after surgery
      demonstrated acceptable graft integration. The patients have now been followed up
      to 5 years. No evidence of relapse has been observed. This technique seemed to be
      undemanding, included minimal laboratory procedure, and maintained the labial
      mucosa overlying the repositioned segment intact. 

PMID- 24926721
TI  - Surgical therapy of a vertebral artery aneurysm with saccular and fusiform
      segments.
AB  - Vertebral artery aneurysms form a group of aneurysms having high rates of
      rebleeding, morbidity, and mortality, poor treatment outcomes, as well as low
      rate of surgical treatment. Examinations for subarachnoid bleeding revealed a
      vertebral artery aneurysm with a diameter of 12 mm in a 67-year-old man who
      presented with headache. The vertebral artery aneurysm with saccular and fusiform
      segments was shrunk and clipped via lateral left suboccipital approach. No
      neurologic deficit was present at the postoperative period. Control digital
      subtraction angiography showed complete shrinkage of aneurysm with continued
      blood flow and no residue. Clinical findings, treatments, and surgical approaches
      of VA aneurysms are different from anterior and posterior circulation aneurysms.
      Microneurosurgical clipping is the most effective treatment of vertebral artery
      aneurysms in suitable cases. Although endovascular intervention is commonly
      applied as therapeutic modality for patients with vertebral artery aneurysm,
      researchers have also emphasized that saccular vertebral aneurysms with fusiform
      extension can also be surgically treated in suitable cases.

PMID- 24926722
TI  - Duret hemorrhage after lumbar drainage.
AB  - Lumbar drainage (LD) is considered as a simple and effective procedure for the
      treatment of intracerebral hemorrhage with ventricular involvement. However,
      cerebrospinal fluid overdrainage and hypovolemia due to LD could induce severe
      fatal complications, which include transtentorial herniation and infratentorial
      hemorrhage. Here, we describe a 63-year-old man with transtentorial herniations
      and Duret hemorrhage attributable to LD after the operation of thalamic hematoma
      removal. This is probably the first reported case of severe complications of LD.
      Thus, complications related to transtentorial herniations and Duret hemorrhage
      should be kept in mind while performing LD. 

PMID- 24926723
TI  - Lipofibromatous hamartoma of a cranial nerve.
AB  - Lipofibromatous hamartomas (LFHs) are rare benign tumors that typically present
      as slow-growing firm masses in the subcutaneous soft tissue of the extremities.
      These often develop in young adults on the volar aspects of the hands, wrists,
      and forearms along major nerves and their branches. Only a single case of LFH
      growth along a cranial nerve has been reported. A 41-year-old man presented with
      a subcutaneous soft mass of the cheek. Histologically, the mass consisted of a
      proliferating fibrofatty tissue that surrounded and infiltrated the nerve
      structure and it was confirmed to be an LFH. After surgical excision, the patient
      experienced mild facial numbness and motor disturbance on the side ipsilateral to
      the resection. Because complete excision of the mass can cause sensory or motor
      disturbances, an accurate diagnosis and proper subsequent treatment, such as
      partial decompression, are necessary.

PMID- 24926725
TI  - Facial nerve function preservation with vacuum-assisted closure.
AB  - IMPORTANCE: Laboratory and clinical studies have shown that vacuum-assisted
      closure (VAC) therapy increases wound blood flow and granulation tissue formation
      and decreases accumulation of fluid and bacteria. Many publications outline the
      use of VAC dressings in the treatment of sternal, sacral, upper and lower
      extremity, perineal, and abdominal wounds, but few describe its use in the head
      and neck region. No report to date has addressed the use of VAC therapy in
      helping to preserve facial nerve integrity. OBSERVATIONS: We present a case of a
      64-year-old woman who underwent tissue debridement for necrotizing fasciitis of
      the left face, neck, and upper chest. She subsequently had exposed facial nerve
      that was covered with a VAC dressing and demonstrated complete granulation by
      postoperative day 7 with preservation of function. CONCLUSIONS AND RELEVANCE:
      This case highlights the effectiveness of VAC in eliminating infectious material
      and promoting granulation tissue formation. This is the first time that VAC
      therapy has been shown to maintain neural function when placed directly on
      functioning cranial nerves.

PMID- 24926726
TI  - Soft tissue response after chin advancement using two different genioplasty
      techniques: a preliminary technical comparative study.
AB  - PURPOSE: The aim of this study was to evaluate soft tissue response after chin
      advancement using 2 different genioplasty techniques. METHODS: The study included
      8 adult patients who were divided equally into 2 groups: group 1 was surgically
      treated by sliding genioplasty, and group 2 was surgically treated by chin shield
      genioplasty for the correction of retruded or deficient chin. Lateral
      cephalograms were taken twice: immediately preoperative and 6 months
      postoperative. RESULTS: The mean (SD) change of soft tissue pogonion (Pg') was
      4.7 (0.3) mm in group 1, whereas in group 2, the mean (SD) change of soft tissue
      pogonion (Pg') was 6.2 (4.8) mm. The mean (SD) change in the labiomental depth in
      group 1 was 0.9 (0.3) mm, whereas in group 2, it was 0.2 (0.5) mm. So in group 2,
      chin shield genioplasty contributed to a less labiomental fold depth. The ratio
      of soft tissue response to bony movement in the sliding genioplasty technique was
      1:0.83, whereas in the chin shield genioplasty technique, it was 1:0.99.
      CONCLUSIONS: In the chin shield genioplasty technique, the increase in
      labiomental fold depth was less than in the sliding genioplasty technique.

PMID- 24926727
TI  - Impact-generated endolithic habitat within crystalline rocks of the Haughton
      impact structure, Devon Island, Canada.
AB  - The colonization of rocks by endolithic communities is an advantageous trait,
      especially in environments such as hot or cold deserts, where large temperature
      ranges, low water availability, and high-intensity ultraviolet radiation pose a
      significant challenge to survival and growth. On Mars, similar conditions (albeit
      more extreme) prevail. In these environments, meteorite impact structures could
      provide refuge for endolithic organisms. Though initially detrimental to biology,
      an impact event into a rocky body can favorably change the availability and
      habitability of a substrate for endolithic organisms, which are then able to
      (re)colonize microfractures and pore spaces created during the impact. Here, we
      show how shocked gneisses from the Haughton impact structure, Devon Island,
      Canada, offer significant refuge for endolithic communities. A total of 28 gneiss
      samples representing a range of shock states were analyzed, collected from in
      situ, stable field locations. For each sample, the top centimeter of rock was
      examined with confocal scanning laser microscopy, scanning electron microscopy,
      and bright-field microscopy to investigate the relationship of biomass with shock
      level, which was found to correlate generally with increased shock state and
      particularly with increased porosity. We found that gneisses, which experienced
      pressures between 35 and 60 GPa, provide the most ideal habitat for endolithic
      organisms.

PMID- 24926729
TI  - A note on breast cancer trials with pCR-based accelerated approval.
AB  - Accelerated approval by the Food and Drug Administration (FDA), under the
      agency's Fast Track review designation, allows early approval of drugs to treat
      serious diseases and fill an unmet medical need based on a surrogate endpoint. In
      May 2012, FDA issued a draft Guidance for Industry on the accelerated approval of
      breast cancer drugs based on the surrogate endpoint "pathologic complete
      response" (pCR). The research reported in this article investigates potential
      issues in designing clinical studies for pCR-based accelerated approval. The
      correlation between pCR and long-term survival was investigated. Two sample
      comparisons based on a conditional survival model under different assumptions
      were performed and are discussed along with simulation results. The findings from
      this research may shed some light on the implementation of the FDA draft
      guidance. 

PMID- 24926730
TI  - Regulation of silicosis formation by lysophosphatidic acid and its receptors.
AB  - Silicosis is a serious occupational disease characterized by lung fibrosis that
      is caused by long-term inhalation of silica-containing fine particles.
      Lysophosphatidic acid (LPA) and LPA1/3 plays a role in lung fibrosis. Until
      recently, there has been little research investigating the role of LPA and LPA
      receptors (LPAR) in silica-induced development of pulmonary fibrosis. In this
      study, we evaluated the hypothesis that LPA and LPA1/3 may play a role in
      silicosis pathogenesis using rat silicosis models induced by intratracheal
      instillation of silica, and randomly divided into control, silica, and VPC-12249
      groups. LPA serum and bronchoalveolar lavage fluid (BALF) levels were quantified
      by ELISA. alpha-smooth muscle actin (alpha-SMA), type I and III collagen protein
      expression was quantified by western blotting (WB), and type I and III collagen
      mRNAs detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Lung
      hydroxyproline (HYP) levels were detected using alkaline hydrolysis, with
      hematoxylin and eosin (H&E) and picrosirius red staining used for pathological
      examination. In vitro experiments showed that LPA stimulated fibroblasts
      proliferated in a time and dose-dependent manner and promoted expression of alpha
      SMA, and type I and III collagen. Moreover, LPA serum and BALF levels increased
      in silica-instilled rats. In vivo and in vitro experiments revealed that alpha
      SMA expression and collagen deposition reduced significantly after VPC-12249
      treatment, and histopathological results show VPC-12249 alleviates silicosis
      progression. In conclusion, our findings suggest that LPA promotes the
      proliferation, transformation, and collagen synthesis of fibroblasts, and that
      LPA-LPA1/3 are involved in the development of silicosis and may serve as novel
      therapeutic targets for treatment.

PMID- 24926731
TI  - An investigation into the use of 3G mobile communications to provide telehealth
      services in rural KwaZulu-Natal.
AB  - BACKGROUND: We investigated the use of third-generation (3G) mobile
      communications to provide telehealth services in remote health clinics in rural
      KwaZulu-Natal, South Africa. MATERIALS AND METHODS: We specified a minimal set of
      services as our use case that would be representative of typical activity and to
      provide a baseline for analysis of network performance. Services included
      database access to manage chronic disease, local support and management of
      patients (to reduce unnecessary travel to the hospital), emergency care (up to 8
      h for an ambulance to arrive), e-mail, access to up-to-date information (Web),
      and teleclinics. We made site measurements at a representative set of health
      clinics to determine the type of coverage (general packet radio service
      [GPRS]/3G), its capabilities to support videoconferencing (H323 and SkypeTM
      [Microsoft, Redmond, WA]) and audio (Skype), and throughput for transmission
      control protocol (TCP) to gain a measure of application performance. RESULTS: We
      found that none of the remote health clinics had 3G service. The GPRS service
      provided typical upload speed of 44 kilobits per second (Kbps) and download speed
      of 64 Kbps. This was not sufficient to support any form of videoconferencing. We
      also observed that GPRS had significant round trip time (RTT), in some cases in
      excess of 750 ms, and this led to slow start-up for TCP applications.
      CONCLUSIONS: We found audio was always so broken as to be unusable and further
      observed that many applications such as Web access would fail under conditions of
      very high RTT. We found some health clinics were so remote that they had no
      mobile service. 3G, where available, had measured upload speed of 331 Kbps and
      download speed of 446 Kbps and supported videoconferencing and audio at all
      sites, but we frequently experienced 3G changing to GPRS. We conclude that mobile
      communications currently provide insufficient coverage and capability to provide
      reliable clinical services and would advocate dedicated wireless services where
      reliable communication is essential and use of store and forward for mobile
      applications.

PMID- 24926732
TI  - Medication persistence and discontinuation of rivaroxaban versus warfarin among
      patients with non-valvular atrial fibrillation.
AB  - OBJECTIVES: To compare real-world persistence and discontinuation among non
      valvular atrial fibrillation (NVAF) patients on rivaroxaban and warfarin in the
      US. RESEARCH DESIGN AND METHODS: A large nationally representative US claims
      database was used to conduct a retrospective cohort analysis of patients with
      NVAF treated with rivaroxaban or warfarin from 1 July 2010 through 31 March 2013.
      Index date was the date of the first prescription of rivaroxaban or warfarin. All
      patients were followed until the earliest of inpatient death, end of continuous
      enrollment, or end of study period. Rivaroxaban patients were matched 1:1 by
      propensity scores. Medication persistence was defined as absence of refill gap of
      >= 60 days. Discontinuation was defined as no additional refill for at least 90
      days and until the end of follow-up. Cox proportional hazards models were
      estimated to examine the adjusted hazard ratios (aHRs) of rivaroxaban vs.
      warfarin on non-persistence and discontinuation. RESULTS: A total of 32,886 NVAF
      patients on rivaroxaban or warfarin met the study inclusion criteria. Each of the
      7259 rivaroxaban patients identified were matched 1:1 to warfarin patients.
      Patients on rivaroxaban had a significantly better rate of persistence (aHR:
      0.63, 95% CI 0.59-0.68) and lower rate of discontinuation (aHR: 0.54, 95% CI 0.49
      0.58) compared to warfarin recipients. LIMITATIONS: Claims data may have
      contained inaccuracies and miscoding. Confounding may remain even after
      propensity score matching and additional adjustments in model. Refill data may
      not fully reflect actual medication use. Longer follow-up may produce more
      precise estimates of persistence and discontinuation. CONCLUSION: This matched
      cohort analysis indicated that rivaroxaban was associated with significantly
      higher medication persistence and lower discontinuation rates compared to
      warfarin.

PMID- 24926733
TI  - Action plans to reduce hospitalizations for chronic obstructive pulmonary disease
      exacerbations: focus on oral corticosteroids.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with a huge
      burden of suffering and healthcare expenditures. Patients hospitalized due to
      COPD have increased risk of death. Starting in 2015, reimbursements by the
      Centers for Medicaid Medicare Services will be significantly reduced to hospitals
      with excess 30 day readmissions for COPD. Oral corticosteroid (OCS) therapy is
      established in improving outcomes in COPD patients treated in the emergency
      department and hospital. The objective of this article is to review the evidence
      evaluating home OCS treatment of COPD exacerbations as part of a comprehensive
      self-management action plan. METHODS: We reviewed the English literature via
      PubMed, Embase, and Scopus using the search terms: chronic obstructive pulmonary
      disease exacerbations AND: oral corticosteroids, prednisone, prednisolone,
      methylprednisolone, treatment, self-management, disease management, written
      action plans. When pertinent articles were found, we reviewed the relevant
      articles cited. FINDINGS: Two randomized trials enrolling 933 patients provide
      evidence of reduced rates of hospitalization by using comprehensive COPD action
      plans, including OCS therapy. Three trials with 790 patients enrolled did not
      reveal reduced rates of hospitalization. Among all five trials together, there
      were no differences in deaths (76 in the intervention groups [home action plans];
      81 in the usual care groups). Additional studies not assessing hospitalizations
      have found home use of OCSs increases time to the next exacerbation and decreases
      recovery time. CONCLUSION: Further randomized trials are needed to establish that
      home use of OCS therapy, as part of a comprehensive action plan, reduces the rate
      of hospitalizations. Such action plans should include structured patient
      education, early initiation of OCSs, oral antibiotics, and frequent telephone
      reinforcement and support from case management.

PMID- 24926734
TI  - Tapentadol at medium to high doses in patients previously receiving strong
      opioids for the management of cancer pain.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of
      tapentadol (TP) for a period of 4 weeks in patients who were already treated by
      opioids. METHODS: A convenience sample of 30 patients was selected for a
      prospective observational cohort study. Cancer patients who were receiving at
      least 60 mg of oral morphine equivalents were selected. Patients discontinued
      their previous opioid analgesics before starting TP, in doses calculated
      according the previous opioid consumption (1:3.3 ratio with oral morphine
      equivalents). The subsequent doses were changed according to the patients' needs
      for a period of 4 weeks. Oral morphine was offered as a breakthrough pain
      medication. Pain and symptom intensity were recorded at weekly intervals.
      Distress score (DS) was calculated from the sum of symptom intensities. TP opioid
      escalation indexes (TPEI) for the study period were calculated. RESULTS: Nineteen
      patients were male, and the mean age was 63.5 years (+/-11.5). The mean Karnofsky
      status was 62.9 (+/-10). The mean dose of oral morphine equivalents before
      switching to TP was 112 mg (+/-57) and the initial mean dose of TP was 343 mg (+/
      150). Pain intensity significantly decreased. Tapentadol escalation index in
      percentage was 1.26 (TPEI% +/- 2.6) and Tapentadol escalation index in mg was
      2.76 (TPEImg +/- 4.96). No significant relationships were found with primary
      tumor (TPEI%, p = 0.204; TPEImg, p = 0.180), pain mechanism (TPEI%, p = 0.863;
      TPEImg, p = 0.846), age (TPEI%, p = 0.882; TPEImg, p = 0.884), or gender (TPEI%,
      p = 0.287; TPEImg, p = 0.325). DS decreased, but non-significantly (p = 0.1). Ten
      patients did not complete the study period: five patients discontinued TP for
      uncontrolled pain, despite increasing doses of TP over 600 mg/day. Two patients
      discontinued TP for adverse effects and three patients dropped out, one patient
      for poor compliance and two patients for unrecorded reasons. CONCLUSION: In our
      sample, TP used in doses of 350-450 mg/day was well tolerated and effective in
      opioid tolerant patients with cancer pain and could be considered as a flexible
      drug to be used for the management of moderate to severe cancer pain. Like most
      studies in patients with cancer pain, it was limited by its open-label,
      uncontrolled design, the number of patients lost in follow-up, and
      discontinuation of the treatment for several reasons. Further studies in a large
      number of patients should confirm these preliminary results.

PMID- 24926735
TI  - Predictive value of a serum-based proteomic test in non-small-cell lung cancer
      patients treated with epidermal growth factor receptor tyrosine kinase
      inhibitors: a meta-analysis.
AB  - OBJECTIVE: Several studies have demonstrated that a serum-based proteomic test
      (VeriStrat * ) is able to predict the clinical outcome of non-small-cell lung
      cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs). However, these studies have limited power to draw
      a precise conclusion because of their small sample sizes and inconsistent
      results. Therefore, a meta-analysis was carried out in an attempt to provide more
      persuasive evidence. RESEARCH DESIGN AND METHODS: Electronic searches for
      relevant articles in PubMed, Embase, Medline, and Web of Science published up to
      May 2013 were conducted. Stata Statistical Software version 12.0 was applied for
      statistical analysis. The combined hazard ratio (HR) and 95% confidence interval
      (CI) were estimated using fixed-effects models. RESULTS: Eleven cohorts involving
      706 patients collected from seven studies were subjected to final analysis. This
      serum-based proteomic test's 'good' status predicted a better clinical outcome
      with a pooled HR of 0.40 (95% CI 0.32 to 0.49; p < 0.001) for overall survival
      (OS), and 0.49 (95% CI 0.39 to 0.60; p < 0.001) for progression-free survival
      (PFS). There was no significant heterogeneity, but a slight publication bias in
      this study. CONCLUSIONS: Our meta-analysis demonstrated that this serum-based
      proteomic test has a predictive value for NSCLC patients treated with EGFR-TKIs.
      Future data are needed to validate and update our results.

PMID- 24926737
TI  - Effects of music therapy on patient satisfaction and health-related quality of
      life of hospital inpatients.
AB  - The matched-case control study investigated the effect of inpatient music therapy
      (MT), including the gift of a compact disc, on patient satisfaction and quality
      of life. Overall rating of the hospital and likelihood to recommend it (n = 210),
      and SF-12 quality of life scores (n = 160) were compared between groups. Although
      no significant difference in overall hospital rating was found, MT patients'
      recommendation scores were higher (p =.02). The MT patients had marginally better
      quality of life pain scores (p =.06). Integration of MT with inpatient care can
      improve the likelihood that patients will recommend the hospital and may impact
      their perception of pain.

PMID- 24926736
TI  - Optimizing the OR: a bottom-up approach.
AB  - Efficiency in the operating room (OR) has important implications on finances,
      access, and patient and staff satisfaction. UC Davis Medical Center (UCDMC)
      launched an initiative to increase OR efficiency by using multidisciplinary staff
      based teams. The initiative freed up 5,500 annual hours-about 1 hr per operating
      room per day-in the OR by improving the percentage of first case on-time starts,
      reducing OR turnover times, improving scheduling predictability and reducing the
      number of controllable cancellations. Importantly, the process also engrained a
      continuous quality improvement mentality into the medical center's culture.

PMID- 24926738
TI  - The society's view of nursing in Turkey.
AB  - This study was conducted in order to ensure the educational transformation of a
      school of health at a state university, within the scope of the Bologna Process.
      A review of the literature suggests that dependent functions of nursing are
      studied more often than its independent functions, but independent functions of
      nursing are not properly understood by society. The population consisted of 458
      people in Duzce. They were chosen using a stratified sampling method. The
      researchers developed a questionnaire form to use as the data collection tool.
      The data were evaluated by means of descriptive statistics. People living in
      Duzce region believed that nurses primarily perform care activities, that they
      act as assistants to doctors. Nurses who perform practical tasks were given
      positive ratings for their interpersonal communication skills, but the
      participants also expected nursing school to improve educational structuring to
      help nursing students acquire communication skills. Nursing education programs
      must be restructured to improve nursing students' communication skills. It is the
      first step for structuring education program to know what is nursing image within
      society. In light of this approach nursing program can be restructured to local
      tendencies.

PMID- 24926739
TI  - The accountable care organization summit: a white paper on findings, outcomes,
      and challenges.
AB  - The authors sought to explore the implications of the Patient Protection and
      Affordable Care Act's establishment of Accountable Care Organizations (ACO).
      Summit participants, who discussed best practices and issues to be addressed when
      designing and implementing ACOs. Healthcare leaders from across the country in
      charge of running, developing, and/or implementing ACOs for health systems.
      Participants were asked to consider the challenges, benefits, and strategies to
      ACO implementation.

PMID- 24926740
TI  - Effect of salt on the formation of salt-bridges in beta-hairpin peptides.
AB  - Salt-bridges ubiquitously form between oppositely charged moieties in proteins.
      Here we quantify changes in population of salt-bridged beta-hairpin peptides due
      to added salt, and determine the thermodynamic driving forces and cooperativity
      of salt-bridge formation under these conditions. We find only a fraction of salt
      bridged folded conformations at physiologically relevant salt concentrations. 

PMID- 24926742
TI  - Molybdenum disulfide/pyrolytic carbon hybrid electrodes for scalable hydrogen
      evolution.
AB  - The electrochemical generation of hydrogen fuel via the proton reduction in the
      Hydrogen Evolution Reaction (HER) in aqueous media is currently dependent on the
      use expensive noble metal catalysts for which alternatives must be sought.
      Molybdenum disulfide (MoS2) has shown great promise as a suitable electrocatalyst
      in this regard. While many lab-scale experiments on the HER activity of this
      material have demonstrated its viability and explored some fundamental
      mechanistic features of HER at MoS2, these experimental techniques are often ill
      suited to large scale production of such electrodes. In this study we present
      work on the fabrication of MoS2/pyrolytic carbon (PyC) electrodes via vapour
      phase sulfurization of Mo thin films. These hybrid electrodes combine the
      catalytic activity of MoS2 with the conductivity and stability of PyC, whilst
      using industrially compatible processing techniques. Structural defects in the
      sulfur lattice were found to be key catalytically active sites for HER and
      thinner MoS2 films displayed a higher quantity of these defects and, hence, an
      improved HER activity. The observed Tafel slope of 95 mV decade(-1) is comparable
      to previous literature works on MoS2 HER performance.

PMID- 24926741
TI  - Sca-1+ cardiac progenitor cells and heart-making: a critical synopsis.
AB  - The identification, in the adult, of cardiomyocyte turnover events and of cardiac
      progenitor cells (CPCs) has revolutionized the field of cardiovascular medicine.
      However, the low rate of CPCs differentiation events reported both in vitro and
      in vivo, even after injury, raised concerns on the biological significance of
      these subsets. In this Comprehensive Review, we discuss the current understanding
      of cardiac Lin(-)Sca-1(+) cells in light of what is also known for cellular
      compartments with similar phenotypes in other organs. The Lin(-)Sca-1(+) heart
      subset is heterogeneous and displays a mesenchymal profile, characterized by a
      limited ability to generate cardiomyocytes in vitro and in vivo, even after
      injury. There is no evidence for Sca-1 expression in embryonic cardiovascular
      progenitors. In other organs, Sca-1 expression is mainly observed on mesoderm
      derived cells, although it is not restricted to stem/progenitor cell populations.
      It is urgent to determine, at a single cell level, to which extent cardiac Lin(
      )Sca-1(+) cells overlap with the fibroblast compartment. 

PMID- 24926743
TI  - Vitamin D deficiency and adult asthma exacerbations.
AB  - OBJECTIVES: There is growing evidence indicating a connection between vitamin D
      deficiency and the severity of asthma exacerbations. This study seeks to assess
      the relationship between vitamin D deficiency and the number and severity of
      asthma exacerbation in adults. METHODS: A retrospective analysis was conducted in
      92 patients being treated for asthma at the University of New Mexico Adult Asthma
      Clinic. Serum 25-hydroxyvitamin D3 levels were analyzed in adults with mild to
      severe persistent asthma. Using multi-variant modeling, the relationship was
      examined between serum vitamin D levels and the odds of asthma exacerbations
      ranging in severity from moderate to severe over the span of five years. RESULTS:
      This study demonstrates that vitamin D sufficiency was significantly associated
      with a decreased total number of asthma exacerbations (incidence rate ratio
      [IRR]: 0.61, 95% confidence interval [CI]: 0.44-0.84, p = 0.002), decreased total
      severe asthma exacerbations (IRR: 0.41, 95% CI: 0.24-0.72, p = 0.002) and
      decreased emergency room visits (IRR: 0.42, 95% CI: 0.20-0.88, p = 0.023).
      CONCLUSION: Vitamin D deficiency may be linked to the risk of severe asthma
      exacerbations in adults.

PMID- 24926744
TI  - Electrochemical reduction of dioxygen by copper complexes with pyridylalkylamine
      ligands dissolved in aqueous buffer solution: the relationship between activity
      and redox potential.
AB  - The Cu(II)/Cu(I) redox properties and electrochemical O2 reduction activity of a
      series of Cu(II)-complexes with pyridylalkylamine ligands were investigated in a
      neutral buffer solution. The relationship between Cu(II)/Cu(I) redox properties
      and O2 reduction activity was clearly demonstrated by voltammetric analyses. 

PMID- 24926747
TI  - Editorial.

PMID- 24926746
TI  - A comparative study of Ru(II) cyclometallated complexes versus thiocyanated
      heteroleptic complexes: thermodynamic force for efficient dye regeneration in dye
      sensitized solar cells and how low could it be?
AB  - Four novel Ru(II) bipyridyl complexes MH12-15 were synthesized and characterized
      for dye-sensitized solar cells (DSSCs). Their photovoltaic performance including
      incident photon-to-current conversion efficiency (IPCE), total solar-to-power
      conversion efficiency (eta%) and ground and excited state oxidation potentials
      and photoelectrochemical properties were evaluated on mesoporous nanocrystalline
      TiO2 and compared with the benchmark N719-dye under the same experimental
      conditions. MH12-15 showed stronger MLCT with significantly higher molar
      extinction coefficient for the lower energy absorption bands at 553 nm (27,500 M(
      1) cm(-1)), 554 nm (34,605 M(-1) cm(-1)), 577 nm (23,300 M(-1) cm(-1)), and 582
      nm (39,000 M(-1) cm(-1)), respectively, than that of N719 (14,200 M(-1) cm(-1)).
      The introduction of a cyclometallated ligand in dyes MH14 and 15 improved the
      optical properties and red-shifts of 24 nm and 28 nm, respectively, compared to
      the non-cyclometallated analogs MH12 and 13. The red shift in the UV-Vis spectra
      of MH14 and 15 can be attributed to the destabilization of the HOMO t2g of
      Ru(II). However, the destabilization of the HOMO furnished an upward shift of the
      ground state oxidation potentials (GSOPs) of MH14 and 15 at -5.44 eV and -5.36 eV
      against vacuum, respectively, which resulted in a driving force of only 0.22 and
      0.16 eV for regeneration of dyes MH14 and 15, respectively. In the case of NCS
      analogs, MH12 and 13, the GSOPs, however, were -5.56 and -5.51 eV, respectively,
      which produced a driving force of more than 0.25 eV for dye regeneration. The
      nanosecond transient absorbance measurements showed that the time needed for the
      oxidized forms of MH12-MH15 to regenerate the neutral dye is 6 MUs, 4 MUs, 13 MUs
      and 18 MUs, respectively, compared to N719 (2.3 MUs). These kinetic data
      confirmed that the weak thermodynamic force, small negative free energy (
      DeltaG), for regeneration of MH14 and 15 neutral dyes makes the dye regeneration
      process kinetically sluggish, which contributed significantly to the loss of both
      photocurrent and photovoltage. This study clearly elucidated that although
      cyclometallation may produce significantly better light harvesting, the driving
      force of less than 0.25 eV is not sufficiently enough for effective dye
      regeneration.

PMID- 24926745
TI  - Identification of aluminium transport-related genes via genome-wide phenotypic
      screening of Saccharomyces cerevisiae.
AB  - Genome-wide screening using gene deletion mutants has been widely carried out
      with numerous toxicants including oxidants and metal ions. The focus of such
      studies usually centres on identifying sensitive phenotypes against a given
      toxicant. Here, we screened the complete collection of yeast gene deletion
      mutants (5047) with increasing concentrations of aluminium sulphate (0.4, 0.8,
      1.6 and 3.2 mM) in order to discover aluminium (Al(3+)) tolerant phenotypes.
      Fifteen genes were found to be associated with Al(3+) transport because their
      deletion mutants exhibited Al(3+) tolerance, including lem3Delta, hal5Delta and
      cka2Delta. Deletion of CKA2, a catalytic subunit of tetrameric protein kinase
      CK2, gives rise to the most pronounced resistance to Al(3+) by showing
      significantly higher growth compared to the wild type. Functional analysis
      revealed that both molecular regulation and endocytosis are involved in Al(3+)
      transport for yeast. Further investigations were extended to all the four
      subunits of CK2 (CKA1, CKA2, CKB1 and CKB2) and the other 14 identified mutants
      under a spectrum of metal ions, including Al(3+), Zn(2+), Mn(2+), Fe(2+), Fe(3+),
      Co(3+), Ga(3+), Cd(2+), In(3+), Ni(2+) and Cu(2+), as well as hydrogen peroxide
      and diamide, in order to unravel cross-tolerance amongst metal ions and the
      effect of the oxidants. Finally, the implication of the findings in Al(3+)
      transport for the other species like plants and humans is discussed. 

PMID- 24926748
TI  - Anabolic steroid misuse: How much should we know?
AB  - The misuse of anabolic androgenic steroids (AAS) and other performance enhancing
      (ergogenic) drugs remains largely unrecognized by many health professionals. The
      real extent of the problem is unknown, probably as a result of a combination of
      various methodological difficulties. Examples include poor definition of cases,
      obstacle in recruiting large enough samples for longitudinal follow-up, ethical
      issues as AAS are obtained from the black market and the covert nature of the
      problem itself. Our review attempts to alert psychiatrists and mental health
      professionals to the risks associated with these compounds. We cover the
      pharmacology, epidemiology, the use and misuse and relevant complications. 

PMID- 24926749
TI  - Personality disorder ? The rules of engagement.
AB  - This paper sets out the size and pressing nature of the problem of personality
      disorder and attempts to provide clinicians with a coherent strategy for the
      assessment of personality disorder, with special emphasis on determining who
      should be taken on for treatment. 

PMID- 24926750
TI  - A naturalistic study on the criteria of choice of second-generation
      antidepressants: A comparison of venlafaxine and SSRIs in depressed inpatients.
AB  - INTRODUCTION: The objective of this study was to compare, in a naturalistic
      setting, the efficacy and tolerability of selective serotonin reuptake inhibitors
      (paroxetine, sertraline, citalopram) and venlafaxine, in 120 depressed
      inpatients. This paper attempts to review which variables may influence a
      physician's choice of a specific antidepressant for a specific patient. METHOD:
      Patients were assessed using the Hamilton Psychiatric Rating Scale for Depression
      (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical
      Global Impression (CGI) and the Symptoms Check List (SCL-90). The two groups
      under assessment were comparable in all socio-demographic characteristics. We
      used logistic regression analyses to identify variables that differentiate the
      two groups at baseline. This, in turn, would represent those variables with the
      potential to influence a physician's selection of an antidepressant. RESULTS:
      Venlafaxine patients reported significantly worse scores on MADRS at baseline,
      but any difference was no longer present at discharge. We found no significant
      variation in the efficacy of the antidepressants under study and there were no
      differences in the incidence and profiles of adverse events between the groups of
      patients. CONCLUSION: The degree of severity of the actual depressive picture
      appears to influence choice in favour of venlafaxine. However, it appears that
      the choice of SSRIs is more closely linked to patients who present a previous
      history of non-mood psychiatric symptoms.

PMID- 24926751
TI  - The clinical value of risperidone and olanzapine: A meta-analysis of efficacy and
      safety.
AB  - INTRODUCTION: Since 1990 novel antipsychotics have been available to treat
      schizophrenia. Risperidone and olanzapine have emerged as the two most popular
      members of this class. The current report aims to synthesize the clinical trial
      data currently available on these two novel antipsychotics and compare them with
      conventional products in terms of efficacy and safety. METHODS: Published
      randomized clinical trials, which included a risperidone or olanzapine arm, were
      sought through the MEDLINE, EMBASE and PSYCLIT databases. Trials were only
      excluded due to reporting failures or design incompatibilities (not randomized).
      A random effects approach was applied to compare information across trials, and
      meta-regression was used to compare product categories and gain insight into
      patient factors related to clinical outcomes. Outcome variables measured were
      total Positive and Negative Symptom Scale (PANSS) score, withdrawals due to
      inefficacy and use of medication for extrapyramidal symptoms (EPS). RESULTS:
      Risperidone and olanzapine offer advantages over conventional products in terms
      of both efficacy and safety. Of the two novel antipsychotics studied, the
      benefits of risperidone were clearer than those with olanzapine in terms of
      efficacy; this could not be assessed for safety due to inconsistencies in the
      reporting of extrapyramidal symptoms between studies. CONCLUSION: Patients
      receiving novel antipsychotics, particularly risperidone, are likely to gain
      improved control of symptoms of schizophrenia and are less likely to require
      medication to counteract extrapyramidal symptoms than patients receiving
      conventional neuroleptics.

PMID- 24926752
TI  - Ventricular measurements in computed tomography of responders and non-responders
      to donepezil in the treatment of Alzheimer's disease.
AB  - INTRODUCTION: We attempt to see whether the ventricular measurements in routine
      CT scans performed prior to commencing donepezil differed in patients who duly
      responded well and those who did not, and to explore the potential application of
      the findings in clinical practice. METHOD: The study included all patients who
      were prescribed donepezil during a 2-year period in Warrington ( n =59). Two
      groups of patients were compared in respect of their baseline CT scan ventricular
      measurements: those who improved or remained stable cognitively on donepezil ( n
      =43) and those who declined while on donepezil (MMSE < 10) during the study
      period ( n =16). RESULTS: Significant differences in means between the two groups
      were found in relation to the bicaudate span and bicaudate ratio. Of ventricular
      measurements, only the bicaudate parameters were significantly correlated with
      the baseline Mini Mental State Examination (MMSE) score as well as the rate of
      decline in cognitive function during the study period ( P < 0.05). CONCLUSION:
      Baseline bicaudate diameter and ratio may be of some value if included in the
      initial assessment of patients on donepezil. These measurements, in conjunction
      with other cognitive and functional assessments, may prove helpful in deciding
      whether to commence treatment, and give a rough guide to the outcome. Future
      studies, with sufficient statistical power, are necessary to explore the use of
      ventricular parameters in predicting and monitoring patients' response to current
      and future pharmacological treatment in Alzheimer's disease.

PMID- 24926753
TI  - The onset and longitudinal course of a man-made post-traumatic morbidity:
      Survivors of the Sivas disaster.
AB  - INTRODUCTION: This study examined the onset and 18-month longitudinal course of
      post-traumatic stress disorder morbidity in 79 people who were exposed to the man
      mad "Sivas disaster" in Turkey, which caused 37 deaths and more than 60 injuries.
      METHODS: The people who experienced the trauma were stratified into three groups,
      according to the extent of exposure to the disaster, to find out if the extent
      (severity) of trauma was the main predictor of onset and chronicity. Another aim
      of the study was to detect different patterns of post-traumatic morbidity and to
      see how Post-Traumatic Stress Disorder (PTSD) fluctuates in response to related
      stimuli such as the anniversary of the event and the result of the court hearings
      related to the event. RESULTS: Contrary to theoretical knowledge and
      expectations, there were no significant differences in the emergence of acute
      PTSD between the three groups: that is, PTSD emerged in all the groups, and
      higher extent of trauma did not predict higher onset of acute PTSD. Differences
      emerged throughout further stages of the study; higher extent of trauma resulted
      in a higher number of chronic cases and thus extent of trauma was one of the
      predictors of chronicity. Interestingly, up to ten patterns (subgroups) of PTSD
      against the expectation of only three (acute, chronic and delayed) emerged during
      the course of the study. Contrary to expectations, the delayed pattern of
      morbidity was more common than the chronic and acute forms in one of the study
      groups.

PMID- 24926754
TI  - Natural history of affective disorders: Comorbidity as a predictor of suicide
      attempts.
AB  - OBJECT: Comorbidity of psychiatric illnesses and substance misuse can lead to an
      increase in suicide attempts. METHOD: Retrospective data collection from case
      notes of 81 consecutive admissions to an acute psychiatric ward. Previous
      diagnoses, substance misuse and suicidal attempts were all examined. RESULTS: The
      rate of suicide attempts among all groups was 40.7%. Alcohol abuse or use of
      illegal drugs was reported in 69.7% of suicide attempters. More than half of the
      patients (66.7%) overconsumed alcohol. CONCLUSION: Clinical implication of the
      effect of comorbidity on suicidal behaviour and length of stay are discussed.

PMID- 24926755
TI  - Reboxetine in a patient with seasonal bulimia resistant to SSRIs and light
      therapy.
AB  - There is a phenomenological similarity between seasonal affective disorder and
      bulimia nervosa, as sufferers from both show increased appetite and carbohydrate
      craving and probably share a common dysfunction in brain serotonergic systems.
      Serotonergic compounds and bright light therapy have proven to be an effective
      treatment for both disorders. We describe the case of a woman who suffered from
      seasonal affective disorder and nonpurging bulimia nervosa for 16 years and was
      resistant to treatment regimens with selective serotonin re-uptake inhibitors and
      bright light therapy. She was successfully treated with the selective
      noradrenaline re-uptake inhibitor reboxetine. The authors want to encourage
      clinicians to make attempts to treat seasonal and non-seasonal bulimia with
      selective noradrenergic compounds. 

PMID- 24926756
TI  - Neuroleptic malignant syndrome: Possible induction by olanzapine in a case with
      relapsing catatonia.
AB  - Neuroleptic malignant syndrome is a serious medical condition with a significant
      mortality risk. Although it is less common with the atypical than the typical
      agents, it is described in association with clozapine and olanzapine. This report
      documents a case of possible induction of NMS in a patient with relapsing
      catatonia. 

PMID- 24926757
TI  - Successful treatment of severe parasomnias with paroxetine in a 12-year-old boy.
AB  - Night terrors and somnambulism are parasomnias associated with non-REM sleep.
      Medical treatment is only considered in severe cases with persistent and extended
      symptoms where there is a high risk of self-injury. We report the case of a 12
      year-old boy with severe night terrors and somnambulism whose symptoms completely
      remitted under medication with the selective serotonin re-uptake inhibitor
      paroxetine. Its impact on sleep remains unclear as we were not able to show any
      significant changes in the polysomnographic sleep macroarchitecture. Paroxetine
      might be an alternative to benzodiazepines or tricyclic antidepressants because
      it permits subchronic medication, necessitates little dose titration and is well
      tolerated, with few side-effects, and, in particular, has low sedating
      properties. 

PMID- 24926758
TI  - Acute akathisia and sodium valproate.
AB  - Akathisia is a common and distressing side-effect of a number of psychotropic
      drugs, including neuroleptic medication. We report the case of a 38-year-old
      woman who suffers from bipolar affective disorder and developed acute akathisia
      following the introduction of sodium valproate as a mood stabilizer. The
      medication regimen at the onset of her akathisia is described and discussed with
      particular reference to the aetiology of her akathisia. It is not possible to say
      with certainty if her acute akathisia developed as a sole consequence of sodium
      valproate treatment or as a consequence of a possible synergistic effect of her
      other psychotropic medication, but a sodium-valproate-induced functional
      dopaminergic antagonism mediating her acute akathisia appears likely. 

PMID- 24926759
TI  - Topics in contemporary psychiatric practice: Diagnosing Bipolar Disorder.

PMID- 24926762
TI  - Editorial.

PMID- 24926763
TI  - The relationship between sleep disturbance and depression.
AB  - This paper focuses on several aspects of the relationship between sleep and
      depression, with particular attention to objective factors and subjective
      perceptions. It does not address the effect that antidepressants have on sleep,
      nor does it explore the wider implications of the types and course of depression,
      age, or other psychiatric conditions. "Normal sleep" is explored, examining
      typical sleep architecture in individuals without sleep disorders, psychiatric
      conditions or physical illness. Sleep disorders are reviewed and examined to
      present the nature of the disturbance and the role that they may play in
      depression, with particular attention paid to insomnia. Studies have identified a
      sub-group of insomnia patients (highly distressed poor sleepers), who appear to
      be less satisfied with their sleep quality than "low distressed poor sleepers",
      even though they did not differ on sleep timing perceptions. Recent work has
      shown that depressed individuals to be less satisfied with sleep quality than
      healthy controls, even though they did not differ on sleep timing perceptions.
      The evidence presented here supports the view that subjective sleep perceptions
      play an important role in depression. Poor subjective perceptions of sleep in
      depression may be associated with faulty cognitions. This has been found
      extensively in insomnia, but is under-researched in depression. 

PMID- 24926764
TI  - A review on hyponatremia associated with SSRIs, reboxetine and venlafaxine.
AB  - Hyponatremia, defined as serum sodium below 135 mmol/l, is a potentially life
      threatening condition and was shown to be more frequent in elderly and
      psychiatric patients. In the last years numerous case reports on SSRI- and
      venlafaxine-induced hyponatremia were published indicating a higher incidence
      than previously thought. Only few studies have been performed and the incidence
      reported varies widely from 4.6/1000 people to 25%. It is still unclear if any
      single SSRI shows a higher incidence of hyponatremia than the others. Some data
      suggest that venlafaxine may have a stronger association to hyponatremia than
      SSRIs. Risk factors include age, female sex, low body mass index, severe physical
      illness, history of former hyponatremia and co-medications known to induce
      hyponatremia, especially thiazide diuretics. Symptoms of hyponatremia are usually
      neuropsychiatric (e.g. restlessness, lethargy, cognitive impairment), and any
      worsening in psychiatric symptoms in patients with a corresponding risk-profile
      receiving SSRIs or venlafaxine should give cause to check serum electrolytes.
      Usually SSRI-induced hyponatremia occurs within approximately 30 days and is
      reported to improve after withdrawal of the drug. Further controlled studies to
      confirm the true incidence of hyponatremia due to SSRI or venlafaxine and to
      define predictors more precisely are needed. 

PMID- 24926765
TI  - Comparison between the SCOFF Questionnaire and the Eating Attitudes Test in
      patients with eating disorders.
AB  - OBJECTIVE: The SCOFF was developed as a simple, five-question screening tool for
      eating disorders to be used in primary care. The aim of this study was to examine
      the appropriateness of each question in comparison with the Eating Attitudes Test
      26. METHODS: The SCOFF and the EAT-26 were administered to 80 patients with
      eating disorders who had received treatment from May through October 2003 in
      Japan. RESULTS: The scores of the SCOFF and those of the EAT-26 were positively
      correlated (P<0.001), and each question of the SCOFF was strongly associated with
      different items of the EAT-26. The detection rates with the SCOFF of the patients
      with anorexia nervosa or bulimia nervosa and that of the patients with eating
      disorders not otherwise specified (EDNOS) were 96.2 and 48.1%, respectively. The
      scores of the SCOFF and the values of body mass index were significantly
      correlated (P=0.041), and the detection rate with the SCOFF of patients with low
      body weight and EDNOS was low (10%). CONCLUSION: Each question of the SCOFF has
      been selected appropriately for reflecting characteristics of eating disorders,
      although one question about body weight loss should be modified to detect
      patients with anorexia nervosa more accurately.

PMID- 24926766
TI  - Comorbid personality disorders in subjects with bipolar I disorder.
AB  - Objective. The purpose of this study was to present the frequencies of
      personality disorders in a sample of bipolar I patients and to investigate
      whether the presence of comorbid personality disorders affect the course of
      bipolar illness. METHODS: Seventy euthymic bipolar I patients were assessed using
      the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID
      II). Bipolar patients with comorbid personality disorder were compared with those
      of without personality disorder comorbidity on demographic and clinical
      variables. RESULTS: Forty bipolar I patients (57%) had at least one comorbid
      personality disorder. The most common personality disorder cluster was cluster C
      (36%), followed by cluster B (17%) and cluster A (17%) personality disorders. The
      most prevalent personality disorder in the whole group was obsessive-compulsive
      personality disorder (21%). Patients with comorbid personality disorders had an
      earlier age of onset than those of without comorbidity. CONCLUSION: Although the
      rates of comorbid personality disorders are high in bipolar I patients, the
      presence of comorbidity has no relevant impact on the course of bipolar I
      patients except for earlier age of onset of bipolar I disorder.

PMID- 24926767
TI  - Relapse prevention in schizophrenia: does group family psychoeducation matter?
      One-year prospective follow-up field study.
AB  - Objectives. Relapse prevention is one of the most important goals of long-term
      schizophrenia management, as relapse is both distressing and costly. Family
      intervention supplementation to standard treatment could reduce the relapse rate.
      This study assessed the influence of a short-term, clinically based, and
      profesionally led family psychoeducation programme on a 1-year relapse rate.
      Methods. A total of 120 patients were recruited upon discharge from two
      psychiatric hospitals in Prague: (1) Site A (N=86), where family psychoeducation
      is offered to all patients with schizophrenia, schizoaffective disorder, and
      acute psychotic episode with schizophrenic symptoms; and (2) Site B (N=34), where
      no such programme was offered. Results. Compared to nonparticipants,
      psychoeducation participants had a shorter average length of rehospitalization
      stay (5.89 vs. 17.78 days, P=0.045) in a 1-year follow-up after discharge. The
      probability of rehospitalization during a 1-year follow-up was higher for
      patients from the site that did not provide psychoeducation. Conclusions. A
      shorter average length of rehospitalization of psychoeducation participants, a
      high turnout of first-episode patients, and positive responses of psychoeducation
      participants suggest that family psychoeducation should be supplemented early in
      the course of the illness to achieve favourable treatment outcomes and minimize
      adverse health and the social consequences of schizophrenia. 

PMID- 24926768
TI  - Validation of the 13-Item Beck Depression Inventory in alcohol-dependent people.
AB  - Aims. To validate a self-administered questionnaire (the 13-item Beck Depression
      Inventory) as an instrument for assessing depressive symptoms in alcohol
      dependent people. Design, setting and participants. One hundred and eight
      treatment-seeking alcohol-dependent patients were recruited from a teaching
      hospital substance misuse facility. Measures. The Beck Depression Inventory,
      Montgomery Asberg Depression Rating Scale and Hamilton Rating Scale for
      Depression were administered. Scores from each instrument were compared using
      correlation coefficients. Findings. Correlation between the Beck Depression
      Inventory and Montgomery Asberg Depression Rating Scale was 0.763. The Beck
      Depression Inventory achieved a high degree of consistency/reliability
      (Cronbach's alpha=0.8847). Receiver operated curve analysis gave an optimal cut
      off on the 13-item Beck Depression Inventory of 18/19 out of 39 as a screening
      tool to identify cases with moderate or severe depression. This cut-off gave a
      sensitivity of 79% and a specificity of 79% compared to the Montgomery Asberg
      Depression Rating Scale. The diagnostic efficient was 82% for moderate to severe
      depression compared to the Montgomery Asberg Depression Rating and 85% compared
      to Hamilton Depression Rating Scale. Conclusions. The self-administered Beck
      Depression Inventory is a feasible, valid and reliable alternative to the
      interview for detecting change in depressive symptoms in alcohol-dependent
      people. This would be particularly useful in services with very limited staffing
      time such as primary care. 

PMID- 24926769
TI  - Prevalence of insomnia symptoms: results from an urban district in Ankara, Turkey
      1.
AB  - Objective. Characteristics of insomnia symptoms in Turkey are not well
      established. The goal of this study was to determine the prevalence of insomnia
      and related symptoms in an urban district of Turkey. Method. The study was
      carried out in Ankara, in an urban district with a population of 2665. Out of the
      1332 people in the sample, 1034 in the 15-65 age range were included in the
      study. Interviews were conducted according to the "Sleep Disorders Assessment
      Questionnaire" developed by the researchers. The Insomnia Severity Index (ISI)
      was also given to the subjects with a sleep problem to measure the subjective
      quality and quantity of insomnia symptoms. Results and conclusion. A total of
      29.4% of all participants reported a sleep problem, out of which 23.7% defined
      one or more of the insomnia symptoms which included difficulty initiating sleep
      (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), non
      restorative sleep (NRS) and sleep deprivation (SD). Insomnia risk was found to be
      significantly increased with age, female sex, smoking and chronic medical
      illness. A total of 75.9% of participants who reported insomnia symptoms did not
      seek medical help for their complaint. According to the ISI, among the subjects
      with insomnia symptoms, 79 (32.2%) had subthreshold insomnia, 43 (17.6%) had
      clinical insomnia, 12 (4.9%) had severe clinical insomnia, while 88 (35.9%) did
      not score in the range indicating insomnia. The findings are discussed in the
      light of previous research and in relation to sociocultural factors emphasizing
      the need for public education on sleep disorders as medical conditions. 

PMID- 24926770
TI  - Trends and characteristics of deliberate self-harm hospital presentations in an
      English County.
AB  - Background. This study investigates deliberate self-harm (DSH) presentations to
      Southern Derbyshire hospitals from 1990 to 1997. Methods. Retrospective
      evaluation of deliberate self-harm rates and socio-demographic variables
      associated with DSH in 9961 consecutive attendances at Derby's two district
      general hospitals. Results. A significant rise in the rates of DSH in Derbyshire
      was noted (82%). The gender ratio has changed, with rising numbers of DSH
      episodes in males. The ratio of DSH episodes to the total Accident & Emergency
      (A&E) attendances changed from 1.54 to 2.42, with a 36% (95% CI 32-40%) rise in
      DSH presentations. Overdose remains the most common method of DSH (F = 85%, M =
      78%). Two-thirds of the DSH presentations were first DSH attempts. Conclusions.
      Overall DSH rates are increasing especially in men. In contrast, official suicide
      rates have reduced during the same period. The increase in DSH rates has
      implications for already overworked A&E Departments, as well as other emergency
      and psychiatric services. Service provision and organisation should be reviewed
      in light of this increasing demand. 

PMID- 24926771
TI  - Allergy to drugs: is there an association with mental ill-health?
AB  - Objectives. Hypersensitivity reactions to drugs are not infrequent. A certain of
      anxiety, aggression or depression should be expected in patients with drug
      allergies, as they could experience symptoms ranging from mild to life
      threatening reactions following consumption of drug. However, a literature search
      resulted in very limited data. This study was designed to evaluate the
      psychological status of patients with drug allergy and to assess the
      relationships between psychological evaluations of the patients and, duration of
      drug allergy, type of allergic reaction, hypersensitivity reaction of the type of
      drug involved. Methods. The study group comprised 61 patients (43 F, 18 M), age
      ranging from 16 to 75 years, with reliable history of drug allergy. A total of 55
      healthy subjects (39F, 16M) age ranging from 17 to 70 years served as control
      group. Assessment tools consisted of Beck Depression Inventory (BDI), and
      Speilberger's State-Trait Anxiety Inventory (STAI Tx-2). Results. The prevalence
      of depression and anxiety among patients with drug allergies was not greater than
      that of the controls. There were no associations between the scores of these
      psychological assessments and duration of drug allergy, type of allergic
      reaction, type of drug. Conclusions. Our data suggest that follow-up studies
      including high numbers of patients and patients with specific and potentially
      life-threatening clinical pictures of drug allergies are needed to detect
      clinically relevant associations. 

PMID- 24926772
TI  - Psychiatric characteristics of 100 nonviolent suicide attempters in Hungary.
AB  - BACKGROUND: Previous international and Hungarian studies have shown that around
      90% of persons making suicide attempts had at least one current mental disorder.
      The aim of this study was to investigate the current prevalence of DSM-IV Axis I
      psychiatric diagnoses among nonviolent suicide attempters in Budapest, Hungary.
      METHODS: Using a structured interview (Mini International Neuropsychiatric
      Interview) determining DSM-IV Axis I diagnoses, the authors examined 100
      consecutively contacted nonviolent suicide attempters (68 females and 32 males),
      aged between 14 and 66 (mean: 36.3 years). RESULTS: A total of 64% of the
      subjects were repeated attempters, and the most common method was drug overdose
      (96%), in 21% of cases in combination with alcohol ingestion. A total of 92% of
      the attempters had at least one current DSM-IV Axis I psychiatric diagnosis. In
      87% it was depressive disorder (59% unipolar major depression, 14% bipolar II
      depression and 12% bipolar I depression, 2% dysthymic disorder), in 46% anxiety
      disorders, in 27% substance-use disorder and in 2% psychotic disorder. Sixty
      percent of the attempters received two or more current Axis I diagnoses (35%
      depressive + anxiety disorder only, 15% depressive + substance-related disorder
      only, and 10% depressive + anxiety + substance-related disorder). LIMITATIONS:
      Nonviolent suicide attempters are not representative of all persons with
      attempted suicide and subthreshold Axis I diagnoses were not investigated.
      CONCLUSION: This study supports previous international and Hungarian findings on
      the high prevalence and comorbidity of Axis I mental disorders among persons with
      recent nonviolent suicide attempt.

PMID- 24926773
TI  - Massive uvula oedema during lithium therapy and resolution after lithium
      discontinuation.
AB  - Acute oedema of the uvula is relatively rare, and often idiopathic. There are
      only a few cases reported up to date. This is the first case of oedema in the
      uvula that occurred during lithium treatment of a patient with bipolar-I manic
      disorder. 

PMID- 24926774
TI  - Photostabilization of endogenous porphyrins: excited state quenching by fused
      ring cyanoacrylates.
AB  - Endogenous chromophores in human skin, when exposed to sunlight, generate harmful
      reactive oxygen species (ROS). Protoporphyrin IX (PpIX) is one of the common
      chromophores in human tissue. A series of aromatic cyanoacrylates were tested as
      quenchers of excited singlet and triplet states of PpIX. While the diaryl
      cyanoacrylate () did not quench excited singlet or triplet states of PpIX, some
      cyanoacrylates with fused aromatic rings showed excited singlet state quenching
      rate constants as high as 5 * 10(9) M(-1) s(-1) (acetonitrile solution). In
      addition, one of the fused ring cyanoacrylates () quenches PpIX triplet states
      with a rate constant of 3 * 10(9) M(-1) s(-1). The observed quenching rate
      constants correlated well with the suppression of singlet oxygen generation from
      PpIX under visible light exposure in the presence of dissolved oxygen. This
      photostabilization of endogenous chromophores can prevent or reduce ROS
      generation and perhaps constitute a new approach to mitigating cutaneous
      oxidative stress. 

PMID- 24926776
TI  - The versatility of the temporoparietal fascial graft (TPFG) in orbital implant
      exposure.
AB  - BACKGROUND: The use of TPFGs for hydroxyapatite, porous polyethylene and silicone
      implant exposure has been described previously. To the authors' knowledge, this
      is the first description of this technique for acrylic implant exposure and
      paediatric patients. PURPOSE: To demonstrate the versatility of the TPFG in
      orbital implant exposures of varying duration, implant types and patient age as
      well as for recurrent exposure. METHODS: Retrospective, interventional, non
      comparative case series. RESULTS: Twelve patients (13 grafts) are presented with
      a mean follow-up of 9.5 months. The duration of exposure prior to grafting ranged
      from 1-11 months occurring in bioceramic, hydroxyapatite, porous polyethylene and
      acrylic implant types. There were 2 graft failures (success rate 84.6%), one of
      which was treated with a 2nd TPFG. Two of the cases were from the paediatric age
      group. CONCLUSION: This study provides further supporting evidence for the safety
      and efficacy of the TPFG and demonstrates the use of this graft in a variety of
      different clinical situations.

PMID- 24926775
TI  - Parenting Behavior Mediates the Intergenerational Association of Parent and Child
      Offspring ADHD Symptoms.
AB  - Although there are likely to be multiple mechanisms underlying parent attention
      deficit/hyperactivity disorder (ADHD) symptoms as a key risk factor for offspring
      ADHD, potential explanatory factors have yet to be reliably identified. Given
      that parent ADHD symptoms independently predict parenting behavior and child ADHD
      symptoms, we tested whether individual differences in multiple dimensions of
      positive and negative parenting behavior (i.e., corporal punishment, inconsistent
      discipline, positive parenting behavior, observed negative talk, and observed
      praise) mediated the association between parental and offspring ADHD. We used a
      prospective design that featured predictors (i.e., parent ADHD symptoms) and
      mediators (i.e., parenting behavior) that temporally preceded the outcome (i.e.,
      offspring ADHD symptoms). Using a well-characterized sample of 120 children with
      and without ADHD (ages 5-10 at Wave 1, 7-12 at Wave 2) and their biological
      parents, we examined multimethod (i.e., observed, self-report) measures of
      positive and negative parenting behavior as simultaneous mediators of the
      association of Wave 1 parent and Wave 2 offspring ADHD symptoms. Using a multiple
      mediation framework, consisting of rigorous bootstrapping procedures and
      controlling for parent depression, child's baseline ADHD and oppositional defiant
      disorder, and child's age, corporal punishment significantly and uniquely
      mediated the association of Wave 1 parent ADHD symptoms and Wave 2 offspring
      ADHD. We consider the role of parenting behavior in the intergenerational
      transmission of ADHD as well as implications of these findings for the
      intervention and prevention of childhood ADHD. 

PMID- 24926777
TI  - Individualizing the use of medications in children: making Goldilocks happy.
AB  - To date, implementation of precision medicine for children has been limited.
      Extrapolation of adult experience streamlines pediatric drug development
      programs, and physiologically based pharmacokinetic models aid pediatric dose
      selection on a population basis. To achieve clinically viable individualization
      of drug therapy, genotype-stratified pharmacokinetic studies can efficiently
      characterize the extremes of the dose-exposure relationship. Reducing variability
      in exposure through genotype-based dosing may improve identification of genetic
      factors contributing to response, ultimately improving drug therapy for children.

PMID- 24926778
TI  - Functional gene variants of CYP3A4.
AB  - Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more drugs in
      clinical use than any other foreign compound-metabolizing enzyme in humans.
      Recently, increasing evidence has been found showing that variants in the CYP3A4
      gene have functional significance and--in rare cases--lead to loss of activity,
      implying tremendous consequences for patients. This review article highlights the
      functional consequences of all CYP3A4 variants recognized by the Human Cytochrome
      P450 (CYP) Allele Nomenclature Database.

PMID- 24926779
TI  - Pulmonary penetration of piperacillin and tazobactam in critically ill patients.
AB  - Pulmonary infections in critically ill patients are common and are associated
      with high morbidity and mortality. Piperacillin-tazobactam is a frequently used
      therapy in critically ill patients with pulmonary infection. Antibiotic
      concentrations in the lung reflect target-site antibiotic concentrations in
      patients with pneumonia. The aim of this study was to assess the plasma and
      intrapulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill
      patients administered standard piperacillin-tazobactam regimens. A population PK
      model was developed to describe plasma and intrapulmonary piperacillin and
      tazobactam concentrations. The probability of piperacillin exposures reaching
      pharmacodynamic end points and the impact of pulmonary permeability on
      piperacillin and tazobactam pulmonary penetration was explored. The median
      piperacillin and tazobactam pulmonary penetration ratios were 49.3 and 121.2%,
      respectively. Pulmonary piperacillin and tazobactam concentrations were
      unpredictable and negatively correlated with pulmonary permeability. Current
      piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by
      piperacillin-tazobactam-susceptible organisms in some critically ill patients. 

PMID- 24926780
TI  - Response to "The failing right heart: the neglected ventricle?".

PMID- 24926781
TI  - A rule-based prognostic model for type 1 diabetes by identifying and synthesizing
      baseline profile patterns.
AB  - OBJECTIVE: To identify the risk-predictive baseline profile patterns of
      demographic, genetic, immunologic, and metabolic markers and synthesize these
      patterns for risk prediction. RESEARCH DESIGN AND METHODS: RuleFit is used to
      identify the risk-predictive baseline profile patterns of demographic,
      immunologic, and metabolic markers, using 356 subjects who were randomized into
      the control arm of the prospective Diabetes Prevention Trial-Type 1 (DPT-1)
      study. A novel latent trait model is developed to synthesize these baseline
      profile patterns for disease risk prediction. The primary outcome was Type 1
      Diabetes (T1D) onset. RESULTS: We identified ten baseline profile patterns that
      were significantly predictive to the disease onset. Using these ten baseline
      profile patterns, a risk prediction model was built based on the latent trait
      model, which produced superior prediction performance over existing risk score
      models for T1D. CONCLUSION: Our results demonstrated that the underlying disease
      progression process of T1D can be detected through some risk-predictive patterns
      of demographic, immunologic, and metabolic markers. A synthesis of these patterns
      provided accurate prediction of disease onset, leading to more cost-effective
      design of prevention trials of T1D in the future.

PMID- 24926782
TI  - Usefulness of intestinal fatty acid-binding protein in predicting strangulated
      small bowel obstruction.
AB  - BACKGROUND: The level of intestinal fatty acid-binding protein (I-FABP) is
      considered to be useful diagnostic markers of small bowel ischemia. The purpose
      of this retrospective study was to investigate whether the serum I-FABP level is
      a predictive marker of strangulation in patients with small bowel obstruction
      (SBO). METHODS: A total of 37 patients diagnosed with SBO were included in this
      study. The serum I-FABP levels were retrospectively compared between the patients
      with strangulation and those with simple obstruction, and cut-off values for the
      diagnosis of strangulation were calculated using a receiver operating
      characteristic curve. In addition, the sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) were calculated.
      RESULTS: Twenty-one patients were diagnosed with strangulated SBO. The serum I
      FABP levels were significantly higher in the patients with strangulation compared
      with those observed in the patients with simple obstruction (18.5 vs. 1.6 ng/ml
      p<0.001). Using a cut-off value of 6.5 ng/ml, the sensitivity, specificity, PPV
      and NPV were 71.4%, 93.8%, 93.8% and 71.4%, respectively. An I-FABP level greater
      than 6.5 ng/ml was found to be the only independent significant factor for a
      higher likelihood of strangulated SBO (P =  0.02; odds ratio: 19.826; 95%
      confidence interval: 2.1560 - 488.300). CONCLUSIONS: The I-FABP level is a useful
      marker for discriminating between strangulated SBO and simple SBO in patients
      with SBO.

PMID- 24926783
TI  - Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic
      athletes and non-athletes and are associated with bone density and strength
      estimates.
AB  - Irisin and FGF21 are novel hormones implicated in the "browning" of white fat,
      thermogenesis, and energy homeostasis. However, there are no data regarding these
      hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared
      with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and
      FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore,
      because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may
      directly impact bone, we hypothesized that bone density, structure and strength
      would be positively associated with these hormones in athletes and non-athletes.
      To test our hypotheses, we studied 85 females, 14-21 years [38 AA, 24 EA and 23
      non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body
      composition and bone density were assessed using dual energy X-ray
      absorptiometry, bone microarchitecture using high resolution peripheral
      quantitative CT, strength estimates using finite element analysis, resting energy
      expenditure (REE) using indirect calorimetry and time spent exercising/week by
      history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA.
      AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and
      lean mass. Across subjects, irisin was positively associated with REE and bone
      density Z-scores, volumetric bone mineral density (total and trabecular),
      stiffness and failure load. FGF21 was negatively associated with hours/week of
      exercise and cortical porosity, and positively with fat mass and cortical
      volumetric bone density. Associations of irisin (but not FGF21) with bone
      parameters persisted after controlling for potential confounders. In conclusion,
      irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently
      associated with bone density and strength in athletes. 

PMID- 24926785
TI  - On the crucial cerebellar wound healing-related pathways and their cross-talks
      after traumatic brain injury in Danio rerio.
AB  - Upon injury, the direct damage and the subsequent secondary injury in the brain
      often result in chronic neurological disorders. Due to multifactorial nature of
      secondary injury and subsequent complex cellular responses, much of the
      underlying mechanisms are unclear. This study used an adult zebrafish cerebellum
      injury model to investigate the phenotypes and the secondary injury responses for
      recovery mechanisms of injured brain. Using the time course microarray analysis,
      a candidate protein-protein interaction (PPI) network was refined as cerebellar
      wound healing PPI network by dynamic modeling and big data mining. Pathway
      enrichment and ontological analysis were incorporated into the refined network to
      highlight the main molecular scheme of cerebellar wound healing. Several
      significant pathways, including chemokine, Phosphatidylinositide 3-kinases, and
      axon guidance signaling pathway and their cross-talks through PI3K, PAK2, and
      PLXNA3 were identified to coordinate for neurogenesis and angiogenesis, which are
      essential for the restoration of the injured brain. Our finding provides an
      insight into the molecular restoration mechanisms after traumatic brain injury,
      and open up new opportunity to devise the treatment for traumatic brain injury in
      human. 

PMID- 24926786
TI  - Global genome response of Escherichia coli O157?H7 Sakai during dynamic changes
      in growth kinetics induced by an abrupt temperature downshift.
AB  - Escherichia coli O157?H7 is a mesophilic food-borne pathogen. We investigated the
      growth kinetics of E. coli O157?H7 Sakai during an abrupt temperature downshift
      from 35 degrees C to either 20 degrees C, 17 degrees C, 14 degrees C or 10
      degrees C; as well as the molecular mechanisms enabling growth after cold stress
      upon an abrupt downshift from 35 degrees C to 14 degrees C in an integrated
      transcriptomic and proteomic analysis. All downshifts caused a lag period of
      growth before growth resumed at a rate typical of the post-shift temperature. Lag
      and generation time increased with the magnitude of the shift or with the final
      temperature, while relative lag time displayed little variation across the test
      range. Analysis of time-dependent molecular changes revealed, in keeping with a
      decreased growth rate at lower temperature, repression of genes and proteins
      involved in DNA replication, protein synthesis and carbohydrate catabolism.
      Consistent with cold-induced remodelling of the bacterial cell envelope,
      alterations occurred in the expression of genes and proteins involved in
      transport and binding. The RpoS regulon exhibited sustained induction confirming
      its importance in adaptation and growth at 14 degrees C. The RpoE regulon was
      transiently induced, indicating a potential role for this extracytoplasmic stress
      response system in the early phase of low temperature adaptation during lag
      phase. Interestingly, genes previously reported to be amongst the most highly up
      regulated under oxidative stress were consistently down-regulated. This
      comprehensive analysis provides insight into the molecular mechanisms operating
      during adaptation of E. coli to growth at low temperature and is relevant to its
      physiological state during chilling in foods, such as carcasses. 

PMID- 24926787
TI  - Axl receptor tyrosine kinase is a novel target of apigenin for the inhibition of
      cell proliferation.
AB  - The Axl receptor tyrosine kinase (RTK), along with Tyro 3 and Mer, belongs to the
      TAM subfamily that promotes survival, stimulates proliferation and/or inhibits
      apoptosis. In various types of human cancer, including breast, lung and prostate
      cancer, Axl expression is increased and correlates with an advanced clinical
      stage. In this study, we examined whether apigenin has an effect on Axl
      expression, which in turn can affect cell proliferation. The treatment of the non
      small cell lung cancer (NSCLC) cells, A549 and H460, with apigenin decreased Axl
      mRNA and protein expression in a dose-dependent manner. Axl promoter activity was
      also inhibited by apigenin, indicating that apigenin suppressed Axl expression at
      the transcriptional level. Upon treatment with apigenin, the viability of both
      the A549 and H460 cells was gradually decreased and the anti-proliferative
      effects were further confirmed by the dose-dependent decrease in the clonogenic
      ability of the apigenin-treated cells. Subsequently, we found that the viability
      and clonogenic ability of the cells treated with apigenin was less or more
      affected by transfection of the cells with a Axl-expressing plasmid or Axl
      targeting siRNA, compared to transfection with the empty vector or control siRNA,
      respectively. In addition, apigenin increased the expression of p21, a cyclin
      dependent kinase inhibitor, but reduced the expression of X-linked inhibitor of
      apoptosis protein (XIAP). These cell cycle arrest and pro-apoptotic effects of
      apigenin were also attenuated or augmented by the up- or downregulation of Axl
      expression, respectively, which suggests that Axl is a novel target of apigenin
      through which it exerts its inhibitory effects on cell proliferation. Taken
      together, our data indicate that apigenin downregulates Axl expression, which
      subsequently results in the inhibition of NSCLC cell proliferation through the
      increase and decrease of p21 and XIAP expression, respectively.

PMID- 24926788
TI  - N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein
      response and results in hypometabolism and tolerance to hypothermia.
AB  - AIM: N-acyl dopamines (NADD) are gaining attention in the field of inflammatory
      and neurological disorders. Due to their hydrophobicity, NADD may have access to
      the endoplasmic reticulum (ER). We therefore investigated if NADD induce the
      unfolded protein response (UPR) and if this in turn influences cell behaviour.
      METHODS: Genome wide gene expression profiling, confirmatory qPCR and reporter
      assays were employed on human umbilical vein endothelial cells (HUVEC) to
      validate induction of UPR target genes and UPR sensor activation by N-octanoyl
      dopamine (NOD). Intracellular ATP, apoptosis and induction of thermotolerance
      were used as functional parameters to assess adaptation of HUVEC. RESULTS: NOD,
      but not dopamine dose dependently induces the UPR. This was also found for other
      synthetic NADD. Induction of the UPR was dependent on the redox activity of NADD
      and was not caused by selective activation of a particular UPR sensor. UPR
      induction did not result in cell apoptosis, yet NOD strongly impaired cell
      proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of
      HUVEC with low NOD concentration showed decreased intracellular ATP concentration
      paralleled with activation of AMPK. These cells were significantly more resistant
      to cold inflicted injury. CONCLUSIONS: We provide for the first time evidence
      that NADD induce the UPR in vitro. It remains to be assessed if UPR induction is
      causally associated with hypometabolism and thermotolerance. Further
      pharmacokinetic studies are warranted to address if the NADD concentrations used
      in vitro can be obtained in vivo and if this in turn shows therapeutic efficacy.

PMID- 24926789
TI  - Global metabolomic analyses of the hemolymph and brain during the initiation,
      maintenance, and termination of pupal diapause in the cotton bollworm,
      Helicoverpa armigera.
AB  - A strategy known as diapause (developmental arrest) has evolved in insects to
      increase their survival rate under harsh environmental conditions. Diapause
      causes a dramatic reduction in the metabolic rate and drastically extends
      lifespan. However, little is known about the mechanisms underlying the metabolic
      changes involved. Using gas chromatography-mass spectrometry, we compared the
      changes in the metabolite levels in the brain and hemolymph of nondiapause- and
      diapause-destined cotton bollworm, Helicoverpa armigera, during the initiation,
      maintenance, and termination of pupal diapause. A total of 55 metabolites in the
      hemolymph and 52 metabolites in the brain were detected. Of these metabolites, 21
      and 12 metabolite levels were altered in the diapause pupal hemolymph and brain,
      respectively. During diapause initiation and maintenance, the number of
      metabolites with increased levels in the hemolymph of the diapausing pupae is far
      greater than the number in the nondiapause pupae. These increased metabolites
      function as an energy source, metabolic intermediates, and cryoprotectants. The
      number of metabolites with decreased levels in the brain of diapausing pupae is
      far greater than the number in the nondiapause pupae. Low metabolite levels are
      likely to directly or indirectly repress the brain metabolic activity. During
      diapause termination, most of the metabolite levels in the hemolymph of the
      diapausing pupae rapidly decrease because they function as energy and metabolic
      sources that promote pupa-adult development. In conclusion, the metabolites with
      altered levels in the hemolymph and brain serve as energy and metabolic resources
      and help to maintain a low brain metabolic activity during diapause. 

PMID- 24926790
TI  - Demographic status and genetic tagging of endangered capercaillie in NW Spain.
AB  - Counting rare and elusive animals and evaluating their demographic status, are
      fundamental yet challenging aspects of population ecology and conservation
      biology. We set out to estimate population size (Nc), genetic effective
      population size (Ne gen), sex ratio, and movements based on genetic tagging for
      the threatened Cantabrian capercaillie. We used 9 microsatellite loci to genotype
      134 droppings collected at 34 display areas during the breeding season. Using
      genetic capture-mark-recapture, we estimated 93 individuals (Nc, 95% CI: 70-116)
      in an area of about 500 km2, with sex ratio biased towards males (1?1.6).
      Estimated Ne gen (35.5) was 38% of Nc, notably higher than the published average
      in wild populations. This capercaillie population is small and well within
      concern in terms of population viability. By genetic tagging, we detected mostly
      short movements; just a few males were recaptured between contiguous display
      areas. Non-invasive surveys of endangered populations have a great potential, yet
      adequate sample size and location are key to obtain reliable information on
      conservation status. 

PMID- 24926791
TI  - Functional molecular lumino-materials to probe serum albumins: solid phase
      selective staining through noncovalent fluorescent labeling.
AB  - Selective staining of human serum albumin protein in gel electrophoresis over
      wide range of other protein(s) is extremely important because it contains more
      than 60% volume of serum fluid in human body. Given the nonexistence of suitable
      dye materials for selective staining of serum albumins in gel electrophoresis, we
      report a new class of easy synthesizable and low molecular weight staining agents
      based on 3-amino-N-alkyl-carbazole scaffold for selective staining of serum
      albumins in solid phase. A detailed structure-efficiency relationship (SER) study
      enabled us to develop two such potent functional molecular probes which stain
      both human and bovine serum albumin selectively in gel electrophoresis in the
      presence of other proteins and enzymes. The present gel staining process was
      found to be very simple and less time-consuming as compared to the conventional
      coomassie blue staining which in turn makes these probes a new class of serum
      albumin-specific staining materials in proteome research. Moreover, these
      molecular lumino-materials can detect serum albumins at subnanomolar level in the
      presence of broad spectrum of other proteins/enzymes in aqueous buffer (99.9%
      water, pH = 7.3) keeping the protein secondary structure intact. Our experimental
      and the docking simulation results show that these probes bind preferentially at
      'binding site I' of both the serum proteins. 

PMID- 24926792
TI  - Increased tolerance and resistance to virus infections: a possible factor in the
      survival of Varroa destructor-resistant honey bees (Apis mellifera).
AB  - The honey bee ectoparasitic mite, Varroa destructor, has a world-wide
      distribution and inflicts more damage than all other known apicultural diseases.
      However, Varroa-induced colony mortality is more accurately a result of secondary
      virus infections vectored by the mite. This means that honey bee resistance to
      Varroa may include resistance or tolerance to virus infections. The aim of this
      study was to see if this is the case for a unique population of mite-resistant
      (MR) European honey bees on the island of Gotland, Sweden. This population has
      survived uncontrolled mite infestation for over a decade, developing specific
      mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored
      late season virus infections, Varroa mite infestation and honey bee colony
      population dynamics in the Gotland MR population and compared this to mite
      susceptible (MS) colonies in a close by apiary. From summer to autumn the
      deformed wing virus (DWV) titres increased similarly between the MR and MS
      populations, while the black queen cell virus (BQCV) and sacbrood virus (SBV)
      titres decreased substantially in the MR population compared to the MS population
      by several orders of magnitude. The MR colonies all survived the following winter
      with high mite infestation, high DWV infection, small colony size and low
      proportions of autumn brood, while the MS colonies all perished. Possible
      explanations for these changes in virus titres and their relevance to Varroa
      resistance and colony winter survival are discussed. 

PMID- 24926793
TI  - AKAP5 keeps L-type channels and NFAT on their toes.
AB  - In this issue of Cell Reports, Murphy et al. and Dittmer et al. present exciting
      new insight into the regulation of Ca2+ influx via the L-type Ca2+ channel Cav1.2
      and how increased Ca2+ influx translates into localized activation of the nuclear
      transcription factor NFAT upon depolarization in neurons.

PMID- 24926794
TI  - Lewis base catalyzed, enantioselective, intramolecular sulfenoamination of
      olefins.
AB  - A method for the enantioselective, intramolecular sulfenoamination of various
      olefins has been developed using a chiral BINAM-based selenophosphoramide, Lewis
      base catalyst. Terminal and trans disubstituted alkenes afforded pyrrolidines,
      piperidines, and azepanes in high yields and high enantiomeric ratios via
      enantioselective formation and subsequent stereospecific capture of the
      thiiranium intermediate with the pendant tosyl-protected amine. 

PMID- 24926795
TI  - Gli1 contributes to cellular resistance to cisplatin through altered cellular
      accumulation of the drug.
AB  - Cellular resistance to platinum anticancer compounds is governed by no less than
      two molecular processes; DNA repair and cellular accumulation of drug. Gli1 is an
      upstream regulator of nucleotide excision repair, effecting this process through
      c-jun. We, therefore, investigated whether Gli1 plays a role in cellular
      accumulation of cisplatin. Using a Gli1-specific shRNA, we explored the role of
      Gli1 in the cellular accumulation and efflux of cisplatin, in cisplatin-resistant
      A2780-CP70 human ovarian cancer cells. When Gli1 is inhibited, cellular uptake of
      cisplatin was approximately 33% of the level of uptake under control conditions.
      When Gli1 is inhibited, cellular efflux of cisplatin was completely abrogated,
      over a 12-h period of observation. We assayed nuclear lysates from these cells,
      for the ability to bind the DNA sequence that is the Gli-binding site (GBS) in
      the 5'UTR for each of five known cisplatin transmembrane transporters. Four of
      these transporters are active in cisplatin uptake; and, one is active in
      cisplatin efflux. In each case, nuclear lysate from A2780-CP70 cells binds the
      GBS of the respective cisplatin transport gene. We conclude that Gli1 plays a
      strong role in total cellular accumulation of cisplatin in these cells; and, that
      the combined effects on cellular accumulation of drug and on DNA repair may
      indicate a role for Gli1 in protecting cellular DNA from lethal types of DNA
      damage. 

PMID- 24926796
TI  - Extreme heterogeneity in parasitism despite low population genetic structure
      among monarch butterflies inhabiting the Hawaiian Islands.
AB  - Host movement and spatial structure can strongly influence the ecology and
      evolution of infectious diseases, with limited host movement potentially leading
      to high spatial heterogeneity in infection. Monarch butterflies (Danaus
      plexippus) are best known for undertaking a spectacular long-distance migration
      in eastern North America; however, they also form non-migratory populations that
      breed year-round in milder climates such as Hawaii and other tropical locations.
      Prior work showed an inverse relationship between monarch migratory propensity
      and the prevalence of the protozoan parasite, Ophryocystis elektroscirrha. Here,
      we sampled monarchs from replicate sites within each of four Hawaiian Islands to
      ask whether these populations show consistently high prevalence of the protozoan
      parasite as seen for monarchs from several other non-migratory populations.
      Counter to our predictions, we observed striking spatial heterogeneity in
      parasite prevalence, with infection rates per site ranging from 4-85%. We next
      used microsatellite markers to ask whether the observed variation in infection
      might be explained by limited host movement and spatial sub-structuring among
      sites. Our results showed that monarchs across the Hawaiian Islands form one
      admixed population, supporting high gene flow among sites. Moreover, measures of
      individual-level genetic diversity did not predict host infection status, as
      might be expected if more inbred hosts harbored higher parasite loads. These
      results suggest that other factors such as landscape-level environmental
      variation or colonization-extinction processes might instead cause the extreme
      heterogeneity in monarch butterfly infection observed here. 

PMID- 24926797
TI  - Vibronic Raman scattering at the quantum limit of plasmons.
AB  - We record sequences of Raman spectra at a plasmonic junction formed by a gold AFM
      tip in contact with a silver surface coated with 4,4'-dimercaptostilbene (DMS). A
      2D correlation analysis of the recorded trajectories reveals that the observable
      vibrational states can be divided into subsets, by virtue of the symmetry of DMS
      (C2h). The first set comprises the totally symmetric vibrations of DMS (ag) that
      are neither correlated with each other nor with the fluctuating background,
      assigned to the signature of charge-transfer plasmons mediated by DMS. The second
      set consists of bu modes, which are correlated both with each other and with the
      background. Our findings are rationalized on the basis of the charge-transfer
      theory of Raman scattering and illustrate how current carrying plasmons modulate
      the vibronic coupling terms from which the intensities of the bu states are
      derived. In effect, this study identifies gateway molecular modes for mediating
      charge shuttling across a plasmonic gap. 

PMID- 24926799
TI  - Evaluation of the lethal potency of scorpion and snake venoms and comparison
      between intraperitoneal and intravenous injection routes.
AB  - Scorpion stings and snake bites are major health hazards that lead to suffering
      of victims and high mortality. Thousands of injuries associated with such stings
      and bites of venomous animals occur every year worldwide. In North Africa, more
      than 100,000 scorpion stings and snake bites are reported annually. An
      appropriate determination of the 50% lethal doses (LD50) of scorpion and snake
      venoms appears to be an important step to assess (and compare) venom toxic
      activity. Such LD50 values are also commonly used to evaluate the neutralizing
      capacity of specific anti-venom batches. In the present work, we determined
      experimentally the LD50 values of reference scorpion and snake venoms in Swiss
      mice, and evaluated the influence of two main venom injection routes (i.e.,
      intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50
      values obtained with three collected scorpion venoms indicates that Androctonus
      mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector
      (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo).
      Similar analysis of three representative snake venoms of the Viperidae family
      shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba)
      or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra
      snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in
      agreement with the known severity of cobra-related envenomation. Also, our data
      showed that viper venoms are about three-times less toxic when injected IP as
      compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity
      when injected IP or IV. Overall, this study clearly highlights the usefulness of
      procedure standardization, especially regarding the administration route, for
      evaluating the relative toxicity of individual animal venoms. It also evidenced a
      marked difference in lethal activity between venoms of cobra and vipers, which,
      apart from the nature of toxins, might be attributed to the rich composition of
      high molecular weight enzymes in the case of viper venoms.

PMID- 24926798
TI  - The evolution and appearance of C3 duplications in fish originate an exclusive
      teleost c3 gene form with anti-inflammatory activity.
AB  - The complement system acts as a first line of defense and promotes organism
      homeostasis by modulating the fates of diverse physiological processes. Multiple
      copies of component genes have been previously identified in fish, suggesting a
      key role for this system in aquatic organisms. Herein, we confirm the presence of
      three different previously reported complement c3 genes (c3.1, c3.2, c3.3) and
      identify five additional c3 genes (c3.4, c3.5, c3.6, c3.7, c3.8) in the zebrafish
      genome. Additionally, we evaluate the mRNA expression levels of the different c3
      genes during ontogeny and in different tissues under steady-state and
      inflammatory conditions. Furthermore, while reconciling the phylogenetic tree
      with the fish species tree, we uncovered an event of c3 duplication common to all
      teleost fishes that gave rise to an exclusive c3 paralog (c3.7 and c3.8). These
      paralogs showed a distinct ability to regulate neutrophil migration in response
      to injury compared with the other c3 genes and may play a role in maintaining the
      balance between inflammatory and homeostatic processes in zebrafish. 

PMID- 24926800
TI  - 2014 update on atopic dermatitis in children.
AB  - PURPOSE OF REVIEW: The prevalence of pediatric atopic dermatitis (AD) has
      increased throughout the world, now ranging from 10 to 20% in developed
      countries. Pediatric patients with AD make up a substantial proportion of
      patients seen by general pediatricians, allergists, dermatologists, and other
      specialists. As such, there is a need to optimize understanding and management of
      AD. RECENT FINDINGS: The traditional atopic comorbidities of AD have now expanded
      to include associations with nonatopic conditions such as attention deficit
      hyperactivity disorder. Furthermore, with insights from basic, translational, and
      clinical research, experts have a more comprehensive knowledge of the genetic,
      immunological, and environmental factors influencing the development of AD. With
      this new perception, innovative approaches to the management of AD have developed
      with an emphasis on preventive rather than reactive care. The role of biological
      agents in the treatment of this common, yet chronic, disease of the skin has not
      been clearly elucidated. SUMMARY: There have been several recent breakthroughs in
      the diagnosis, pathophysiology, and management of AD. Despite these advances,
      much work is still needed in order to ensure optimal care for AD sufferers.

PMID- 24926801
TI  - The modulation of the symbiont/host interaction between Wolbachia pipientis and
      Aedes fluviatilis embryos by glycogen metabolism.
AB  - Wolbachia pipientis, a maternally transmitted bacterium that colonizes
      arthropods, may affect the general aspects of insect physiology, particularly
      reproduction. Wolbachia is a natural endosymbiont of Aedes fluviatilis, whose
      effects in embryogenesis and reproduction have not been addressed so far. In this
      context, we investigated the correlation between glucose metabolism and
      morphological alterations during A. fluviatilis embryo development in Wolbachia
      positive (W+) and Wolbachia-negative (W-) mosquito strains. While both strains do
      not display significant morphological and larval hatching differences, larger
      differences were observed in hexokinase activity and glycogen contents during
      early and mid-stages of embryogenesis, respectively. To investigate if glycogen
      would be required for parasite-host interaction, we reduced Glycogen Synthase
      Kinase-3 (GSK-3) levels in adult females and their eggs by RNAi. GSK-3 knock-down
      leads to embryonic lethality, lower levels of glycogen and total protein and
      Wolbachia reduction. Therefore, our results suggest that the relationship between
      A. fluviatilis and Wolbachia may be modulated by glycogen metabolism. 

PMID- 24926803
TI  - Direct synthesis of pentafluoroethyl copper from pentafluoropropionate as an
      economical C2F5 source: application to pentafluoroethylation of arylboronic acids
      and aryl bromides.
AB  - The direct synthesis of pentafluoroethyl copper (CuC2F5) from a cuprate reagent
      and ethyl pentafluoropropionate as one of the most economical and useful
      pentafluoroethyl sources was accomplished. The advantages of this method are; all
      the reagents employed are low-cost and operationally simple, and the CuC2F5
      reagent is prepared in virtually quantitative yield. Furthermore, the CuC2F5
      reagent prepared was successfully applied to two types of pentafluoroethylations
      with arylboronic acids and aryl bromides to provide the pentafluoroethylated
      aromatic products in good-to-excellent yields, including large scale operations. 

PMID- 24926802
TI  - Transient receptor potential channels as targets for phytochemicals.
AB  - To date, 28 mammalian transient receptor potential (TRP) channels have been
      cloned and characterized. They are grouped into six subfamilies on the basis of
      their amino acid sequence homology: TRP Ankyrin (TRPA), TRP Canonical (TRPC), TRP
      Melastatin (TRPM), TRP Mucolipin (TRPML), TRP Polycystin (TRPP), and TRP
      Vanilloid (TRPV). Most of the TRP channels are nonselective cation channels
      expressed on the cell membrane and exhibit variable permeability ratios for
      Ca(2+) versus Na(+). They mediate sensory functions (such as vision, nociception,
      taste transduction, temperature sensation, and pheromone signaling) and
      homeostatic functions (such as divalent cation flux, hormone release, and
      osmoregulation). Significant progress has been made in our understanding of the
      specific roles of these TRP channels and their activation mechanisms. In this
      Review, the emphasis will be on the activation of TRP channels by phytochemicals
      that are claimed to exert health benefits. Recent findings complement the
      anecdotal evidence that some of these phytochemicals have specific receptors and
      the activation of which is responsible for the physiological effects. Now, the
      targets for these phytochemicals are being unveiled; a specific hypothesis can be
      proposed and tested experimentally to infer a scientific validity of the claims
      of the health benefits. The broader and pressing issues that have to be addressed
      are related to the quantities of the active ingredients in a given preparation,
      their bioavailability, metabolism, adverse effects, excretion, and systemic
      versus local effects.

PMID- 24926804
TI  - Near-infrared light responsive synthetic c-di-GMP module for optogenetic
      applications.
AB  - Enormous potential of cell-based therapeutics is hindered by the lack of
      effective means to control genetically engineered cells in mammalian tissues.
      Here, we describe a synthetic module for remote photocontrol of engineered cells
      that can be adapted for such applications. The module involves photoactivated
      synthesis of cyclic dimeric GMP (c-di-GMP), a stable small molecule that is not
      produced by higher eukaryotes and therefore is suitable for orthogonal
      regulation. The key component of the photocontrol module is an engineered
      bacteriophytochrome diguanylate cyclase, which synthesizes c-di-GMP from GTP in a
      light-dependent manner. Bacteriophytochromes are particularly attractive
      photoreceptors because they respond to light in the near-infrared window of the
      spectrum, where absorption by mammalian tissues is minimal, and also because
      their chromophore, biliverdin IXalpha, is naturally available in mammalian cells.
      The second component of the photocontrol module, a c-di-GMP phosphodiesterase,
      maintains near-zero background levels of c-di-GMP in the absence of light, which
      enhances the photodynamic range of c-di-GMP concentrations. In the E. coli model
      used in this study, the intracellular c-di-GMP levels could be upregulated by
      light by >50-fold. Various c-di-GMP-responsive proteins and riboswitches
      identified in bacteria can be linked downstream of the c-di-GMP-mediated
      photocontrol module for orthogonal regulation of biological activities in mammals
      as well as in other organisms lacking c-di-GMP signaling. Here, we linked the
      photocontrol module to a gene expression output via a c-di-GMP-responsive
      transcription factor and achieved a 40-fold photoactivation of gene expression. 

PMID- 24926805
TI  - Cardio-oncology issues among pediatric cancer and stem cell transplant survivors.
AB  - Improvements in the survival of children and adolescents diagnosed with cancer
      have resulted in a growing population of childhood, adolescent and adult cancer
      and stem cell transplant survivors. Approximately two thirds of these survivors
      will experience at least 1 late effect of their treatment, and about one third
      will experience a late effect that is severe or life threatening. Childhood
      cancer survivors are at high risk for development of severe cardiac disease,
      particularly after anthracycline and/or radiation exposure. Cardiotoxicity can
      present as early cardiac dysfunction during or shortly after therapy or as
      chronic impairment of cardiac function several years after treatment. Attempts to
      minimize serious adverse effects have included reduction of high-dose
      chemotherapy, particularly anthracycline dosing to <350 mg/m, use of
      cardioprotective agents such as dexrazoxane and decreased radiation dosing and
      radiation fields. There have been no convincing data showing medical
      interventions that can reliably slow or reverse cardiotoxicity in treated
      patients, which therefore warrants further studies looking at the use of beta
      blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, or newer agents either prior to or following the discovery of heart
      damage. Emphasis on the prevention of further damage is critical and can be
      accomplished through aggressive surveillance, including screening for lipid
      abnormalities, cardiac biomarkers such as troponins and B-type natriuretic
      peptides, hypertension, diabetes and obesity as well as the use of
      echocardiography and cardiac magnetic resonance imaging to identify abnormalities
      early in their course. Here, we provide an overview of the field of cardio
      oncology to stimulate interest among cardiologists. 

PMID- 24926806
TI  - Cardiovascular disease and hepatitis C virus infection: an irrelevant statement
      or a hot relationship?
AB  - Hepatitis C virus (HCV) is well known for being the leading cause of
      hepatocellular carcinoma and cirrhosis, contributing to a devastating array of
      metabolic dysfunctions associated with hepatic failure. However, the cardiac
      manifestations of HCV and chronic hepatitis C (CHC) are being explored, thus
      illuminating the connection between HCV infection and cardiac disease. Although
      not all studies agree, the evidence in favor of CHC promoting major risk factors
      for cardiovascular disease such as hypertension, insulin resistance, diabetes
      mellitus, and atherosclerosis is compelling. Similarly, properly warranted
      attention is being guided towards CHC as an independent risk factor for the
      development of atherosclerotic heart disease and cardiomyopathy. This review
      provides a synopsis on the relationship between (HCV) infection and cardiac
      disease, emphasizing on some of the key possible mechanisms and population
      derived data. 

PMID- 24926807
TI  - Jatrophane diterpenes as inhibitors of chikungunya virus replication: structure
      activity relationship and discovery of a potent lead.
AB  - Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia
      amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led
      to the isolation of six new (1-4, 9, and 10) and six known (5-7, 8, 11, and 12)
      jatrophane esters. Their planar structures and relative configurations were
      determined by extensive spectroscopic analysis, and their absolute configurations
      by X-ray analysis. These compounds were investigated for selective antiviral
      activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus,
      and HIV-1 and HIV-2 viruses. Compound 3 was found to be the most potent and
      selective inhibitor of the replication of CHIKV and of HIV-1 and HIV-2 (EC50 =
      0.76, IC50 = 0.34 and 0.043 MUM, respectively). A preliminary structure-activity
      relationship study demonstrated that potency and selectivity are very sensitive
      to the substitution pattern on the jatrophane skeleton. Although replication
      strategies of CHIK and HIV viruses are quite different, the mechanism of action
      by which these compounds act may involve a similar target for both viruses. The
      present results provide additional support for a previous hypothesis that the
      anti-CHIKV activity could involve a PKC-dependent mechanism. 

PMID- 24926808
TI  - Decreased immunoglobulin E (IgE) binding to cashew allergens following sodium
      sulfite treatment and heating.
AB  - Cashew nut and other nut allergies can result in serious and sometimes life
      threatening reactions. Linear and conformational epitopes within food allergens
      are important for immunoglobulin E (IgE) binding. Methods that disrupt allergen
      structure can lower IgE binding and lessen the likelihood of food allergy
      reactions. Previous structural and biochemical data have indicated that 2S
      albumins from tree nuts and peanuts are potent allergens, and that their
      structures are sensitive to strong reducing agents such as dithiothreitol. This
      study demonstrates that the generally regarded as safe (GRAS) compound sodium
      sulfite effectively disrupted the structure of the cashew 2S albumin, Ana o 3, in
      a temperature-dependent manner. This study also showed that sulfite is effective
      at disrupting the disulfide bond within the cashew legumin, Ana o 2.
      Immunoblotting and ELISA demonstrated that the binding of cashew proteins by
      rabbit IgG or IgE from cashew-allergic patients was markedly lowered following
      treatment with sodium sulfite and heating. The results indicate that
      incorporation of sodium sulfite, or other food grade reagents with similar redox
      potential, may be useful processing methods to lower or eliminate IgE binding to
      food allergens. 

PMID- 24926809
TI  - Effects of interaction between temperature conditions and copper exposure on
      immune defense and other life-history traits of the blow fly Protophormia
      terraenovae.
AB  - Environmental pollution is considered one of the major threats to organisms.
      Direct effects of heavy metal pollution on various life-history traits are well
      recognized, while the effects of potential interactions between two distinct
      environmental conditions on different traits are poorly understood. Here, we have
      tested the effects of interactions between temperature conditions and heavy metal
      exposure on innate immunity and other life-history traits. Maggots of the blow
      fly Protophormia terraenovae were reared on either copper-contaminated or
      uncontaminated food, under three different temperature environments.
      Encapsulation response, body mass, and development time were measured for adult
      flies that were not directly exposed to copper. We found that the effects of
      copper exposure on immunity and other traits are temperature-dependent,
      suggesting that the ability to regulate toxic compounds in body tissues might
      depend on temperature conditions. Furthermore, we found that temperature has an
      effect on sex differences in immune defense. Males had an encapsulation response
      at higher temperatures stronger than that of females. Our results indicate that
      the effects of environmental conditions on different traits are much more
      intricate than what can be predicted. This is something that should be considered
      when conducting immunological experiments or comparing results of previous
      studies. 

PMID- 24926810
TI  - Recombinant Neisseria surface protein A is a potential vaccine candidate against
      Neisseria meningitides serogroup B.
AB  - Neisseria meningitidis is the pathogen of epidemic encephalomyelitis and is
      responsible for permanent damage to the brain and nervous system. In the present
      study, the prokaryotic expression vector pGEX-6p-1/neisseria surface protein A
      (NspA) was constructed and the immune protective effect was investigated with the
      purified recombinant rNspA. Female BALB/c mice were immunized by intraperitoneal
      inoculation of rNspA, glutathione S-transferase (GST) or phosphate-buffered
      saline (PBS). The protection experiment in mice demonstrated that the protection
      rate of the rNspA group was 85% against the N. meningitidis strain MC58, and a
      serum bactericidal assay in vitro revealed that the serum bactericidal titer of
      the rNspA group reached 1:64 following three immunizations. The levels of
      specific immunoglobulin (Ig) A (SIgA), IgG, IgG1, IgG2a, IgG2b and IgG3 of mice
      in the rNspA group peaked at week six and were higher than those in the mice in
      the GST and PBS groups. The levels of stimulation index, interleukin-4 and
      interferon-gamma in the culture supernatant of the spleen lymphocytes of the
      rNspA group increased in a time-dependent manner and were higher than those of
      the mice in the GST and PBS groups over the same period. The results suggested
      that rNspA may induce increased specific humoral and cellular immune responses,
      and that it is effectively protective against N. meningitidis serogroup B in
      mice. The present study offered novel evidence that may lead to the development
      of a novel effective N. meningitidis serogroup B vaccine. 

PMID- 24926811
TI  - Screening for geriatric depression in residential care facilities: a systematic
      narrative review.
AB  - Studies in residential care facilities suggest that routine screening can assist
      in the early detection of geriatric depression. However, the effectiveness of
      screening instruments in residential care in the US and Canada has not been
      adequately evaluated. We conducted a systematic narrative review of the English
      language literature published between 2000 and 2010 on screening instruments used
      for depression detection in older adults living in residential care facilities.
      The review yielded nine scales and their modifications tested in residential
      care, which we evaluated. We provide specific recommendations for the use of
      effective scales and discuss implications for practice, policy and research. 

PMID- 24926812
TI  - High-resolution solid-state oxygen-17 NMR of actinide-bearing compounds: an
      insight into the 5f chemistry.
AB  - A massive interest has been generated lately by the improvement of solid-state
      magic-angle spinning (MAS) NMR methods for the study of a broad range of
      paramagnetic organic and inorganic materials. The open-shell cations at the
      origin of this paramagnetism can be metals, transition metals, or rare-earth
      elements. Actinide-bearing compounds and their 5f unpaired electrons remain
      elusive in this intensive research area due to their well-known high
      radiotoxicity. A dedicated effort enabling the handling of these highly
      radioactive materials now allows their analysis using high-resolution MAS NMR
      (>55 kHz). Here, the study of the local structure of a series of actinide
      dioxides, namely, ThO2, UO2, NpO2, PuO2, and AmO2, using solid-state (17)O MAS
      NMR is reported. An important increase of the spectral resolution is found due to
      the removal of the dipolar broadening proving the efficiency of this technique
      for structural analysis. The NMR parameters in these systems with numerous and
      unpaired 5f electrons were interpreted using an empirical approach. Single-ion
      model calculations were performed for the first time to determine the z component
      of electron spin on each of the actinide atoms, which is proportional to the
      shifts. A similar variation thereof was observed only for the heavier actinides
      of this study. 

PMID- 24926813
TI  - Short linear motifs: ubiquitous and functionally diverse protein interaction
      modules directing cell regulation.

PMID- 24926814
TI  - Relation between cognition and neural connection from injured cingulum to
      brainstem cholinergic nuclei in chronic patients with traumatic brain injury.
AB  - BACKGROUND: This study investigated the relation between cognition and the neural
      connection from injured cingulum to brainstem cholinergic nuclei in patients with
      traumatic brain injury (TBI), using diffusion tensor tractography (DTT). METHODS:
      Among 353 patients with TBI, 20 chronic patients who showed discontinuation of
      both anterior cingulums from the basal forebrain on DTT were recruited for this
      study. The Wechsler Intelligence Scale and the Memory Assessment Scale (MAS;
      short-term, verbal, visual and total memory) were used for assessment of
      cognition. Patients were divided into two groups according to the presence of a
      neural connection between injured cingulum and brainstem cholinergic nuclei.
      RESULTS: Eight patients who had a neural connection between injured cingulum and
      brainstem cholinergic nuclei showed better short-term memory on MAS than 12
      patients who did not (p < 0.05). However, other results of neuropsychological
      testing showed no significant difference (p > 0.05). CONCLUSIONS: Better short
      term memory in patients who had the neural connection between injured cingulum
      and brainstem cholinergic nuclei appears to have been attributed to the presence
      of cholinergic innervation to the cerebral cortex through the neural connection
      instead of the injured anterior cingulum. The neural connection appears to
      compensate for the injured anterior cingulum in obtaining cholinergic
      innervation.

PMID- 24926815
TI  - A mobile phone-based, community health worker program for referral, follow-up,
      and service outreach in rural Zambia: outcomes and overview.
AB  - BACKGROUND: Mobile health (m-health) utilizes widespread access to mobile phone
      technologies to expand health services. Community health workers (CHWs) provide
      first-level contact with health facilities; combining CHW efforts with m-health
      may be an avenue for improving primary care services. As part of a primary care
      improvement project, a pilot CHW program was developed using a mobile phone-based
      application for outreach, referral, and follow-up between the clinic and
      community in rural Zambia. MATERIALS AND METHODS: The program was implemented at
      six primary care sites. Computers were installed at clinics for data entry, and
      data were transmitted to central servers. In the field, using a mobile phone to
      send data and receive follow-up requests, CHWs conducted household health
      surveillance visits, referred individuals to clinic, and followed up clinic
      patients. RESULTS: From January to April 2011, 24 CHWs surveyed 6,197 households
      with 33,304 inhabitants. Of 15,539 clinic visits, 1,173 (8%) had a follow-up
      visit indicated and transmitted via a mobile phone to designated CHWs. CHWs
      performed one or more follow-ups on 74% (n=871) of active requests and obtained
      outcomes on 63% (n=741). From all community visits combined, CHWs referred 840
      individuals to a clinic. CONCLUSIONS: CHWs completed all planned aspects of
      surveillance and outreach, demonstrating feasibility. Components of this pilot
      project may aid clinical care in rural settings and have potential for
      epidemiologic and health system applications. Thus, m-health has the potential to
      improve service outreach, guide activities, and facilitate data collection in
      Zambia.

PMID- 24926816
TI  - Retinal Imaging through Phakic Iris-Claw IOL.
AB  - BACKGROUND: Phakic anterior chamber iris-fixated IOL (PIOL) are established for
      the correction of high myopia. These patients require attention to macular
      pathologies. This study was to evaluate the quality of imaging through the PIOLs.
      METHODS: 54 eyes of 31 myopic and hyperopic patients with Verisyse, Verisyse
      toric, and Veriflex phakic iris-fixated IOL were included. Mean preoperative
      refraction was -11.0 D and +5.7 D, respectively; mean follow-up time was 7.4
      years (5-11 years). A matched control group was formed without PIOL implantation.
      OCT scans were performed and evaluated qualitatively and quantitatively. RESULTS:
      In 52 eyes of 31 patients (96%), a 3D-OCT image and fundus photo could be
      obtained in good quality. Foveal thickness was significantly thicker in the
      myopic patients, whereas all other sectors and total volume had no significant
      difference. CONCLUSIONS: It proved possible to obtain high-resolution scans and
      digital photos of the same quality as without additional phakic IOL.

PMID- 24926817
TI  - Behavior of temperature-responsive copolymer microgels at the oil/water
      interface.
AB  - Herein, we investigate the interfacial behavior of temperature-sensitive aqueous
      microgels on the toluene/water interface. Copolymer microgels based on N
      vinylcaprolactam (VCL) and two acrylamides, N-isopropylacrylamide (NIPAm) and N
      isopropylmethacrylamide (NIPMAm), with various copolymer compositions were used
      in this study. It is revealed that these copolymer microgels have the similar
      internal structure, regardless of the chemical composition. A classic kinetics of
      interfacial tension with three distinct regimes is found in the dynamic
      interfacial tension plots of copolymer microgels, which is similar to inorganic
      nanoparticles and proteins. The influences of the copolymer composition and the
      temperature on the interfacial behavior of microgels are investigated. The
      results show that the interfacial behavior of copolymer microgels at the
      toluene/water interface follows exactly the trend of the volume phase behavior of
      microgels but, on the other hand, strongly depends upon the chemical compositions
      of copolymer microgels. In contrast, with respect to the size range of microgels
      studied here (50-500 nm), the size of the microgel has no influence on the
      interfacial tension. Below the volume phase transition temperature (VPTT), the
      equilibrium interfacial tensions of all microgel systems decrease as the
      temperature increases. Above VPTT, the equilibrium interfacial tension remains at
      a certain level for poly(N-vinylcaprolactam) (PVCL)- and poly(N
      isopropylmethacrylamide) (PNIPMAm)-rich microgel systems and increases slightly
      for poly(N-isopropylacrylamide) (PNIPAm)-rich microgel systems. The evolution of
      dynamic interfacial tension for microgel solutions against toluene at T < VPTT is
      faster than that at T > VPTT, because of the reduced deformability of the
      microgel with the increase of the temperature. The softer microgels with lower
      cross-linking degrees exhibit faster kinetics of reduction of interfacial tension
      compared to those with more cross-linked degrees, which strongly supports the
      deformation-controlled interfacial behavior of microgels. 

PMID- 24926818
TI  - Economic burden of brain metastases among patients with metastatic melanoma in a
      USA managed care population.
AB  - Malignant melanoma patients frequently relapse with metastases in the brain,
      making it the third most common cancer-causing brain metastases in the USA.
      Management of brain metastases remains challenging because of the rapid
      progression of disease and ineffectiveness of conventional therapies. This
      retrospective study, with a 'pre/post' design, quantifies the economic burden of
      brain metastases among melanoma patients in the USA. A large managed-care
      insurance claims database (2000 Q1-2011 Q3) was used to identify patients with
      melanoma and brain metastases. The preperiod was defined as the 6 months before
      the index date (diagnosis of first observed brain metastases) and postperiod as
      the period following the index date up to 12 months. All-cause and brain
      metastasis-related healthcare resource utilization and healthcare costs were
      compared on a per-patient-per-month (PPPM) basis between preperiods and
      postperiods. The study included 6076 patients (mean age 63.4 years); 57.6% were
      men. Significant differences (P<0.0001) were observed between the postperiods and
      preperiods in the mean all-cause and brain metastasis-related PPPM
      hospitalizations and emergency department and outpatient visits. Significant
      postperiod versus preperiod differences were also observed in the PPPM mean
      (standard error) all-cause healthcare costs [total: $14 489 ($231) vs. $7277
      ($116); inpatient: $6330 ($195) vs. $1900 ($69); outpatient: $6609 ($102) vs.
      $4449 ($79); P<0.0001 for all] and brain metastasis-related costs [total: $6542
      ($145) vs. $1933 ($62); inpatient: $2976 ($118) vs. $472 ($39); outpatient: $3451
      ($76) vs. $1413 ($47); P<0.0001 for all]. Radiotherapy was the most common
      treatment. The economic burden associated with brain metastases in melanoma is
      significant and underscores the need for newer therapies to improve outcomes in
      these patients. 

PMID- 24926819
TI  - Increased risk of developing cutaneous malignant melanoma is associated with
      variation in pigmentation genes and VDR, and may involve epistatic effects.
AB  - Cutaneous malignant melanoma (CMM) is a malicious human skin cancer that
      primarily affects individuals with light pigmentation and heavy sun exposure, but
      also has a known familial association. Multiple genes and polymorphisms have been
      reported as low-penetrance susceptibility loci for CMM. Here, we examined 33
      candidate polymorphisms located in 11 pigmentation genes and the vitamin D
      receptor gene (VDR) in a population of 130 cutaneous melanoma patients and 707
      healthy controls. The genotypes obtained were evaluated for main association
      effects and potential gene-gene interactions. MC1R, TYR, VDR and SLC45A2 genes
      were found to be associated with CMM in our population. The results obtained for
      major function MC1R mutations were the most significant [with odds ratio
      (OR)=1.787, confidence interval (CI)=1.320-2.419 and P=1.715(-4)], followed by
      TYR (rs1393350) (with OR=1.569, CI=1.162-2.118, P=0.003), VDR (GCCC haplotype in
      rs2238136-rs4516035-rs7139166-rs11568820 block) (with OR=5.653, CI=1.794-17.811,
      P=0.003) and SLC45A2 (rs16891982) (with OR=0.238, CI=0.057-0.987, P=0.048). The
      study also detected significant intermolecular epistatic effects between MC1R and
      TYR, SLC45A2 and VDR, HERC2 and VDR, OCA2 and TPCN2, as well as intramolecular
      interactions between variants within the genes MC1R and VDR. In the final
      multivariate logistic regression model for CMM development, only the gene-gene
      interactions discovered remained significant, showing that epistasis may be an
      important factor in the risk of melanoma.

PMID- 24926820
TI  - Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid
      in a cellular model of Cushing's disease mediates the inhibition of cell
      proliferation and ACTH secretion without a complete corticotroph-to-melanotroph
      transdifferentiation.
AB  - Cushing's disease (CD) is a rare condition in which hypercortisolemia is
      secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is
      associated with significant morbidity and mortality, and a safe therapy that
      effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and
      dopamine agonists (DAs) have recently been considered as monotherapy in CD
      patients, and satisfactory results have been reported, albeit in a limited number
      of patients. Given the permissive role of RA on the dopamine receptor type-2
      (DRD2), the aim of the present study was to see whether a combination of 9-cis RA
      and the DA bromocriptine (Br) might represent a possible treatment for CD. Here
      we show that 9-cis RA induces a functional DRD2 in the pituitary corticotroph
      cell line AtT20, and increases cell sensitivity to Br via a mechanism only
      partially related to corticotroph-to-melanotroph transdifferentiation. In
      addition, 9-cis RA and Br act synergistically to modulate cell viability, with
      favorable implications for clinical use. In nearly 45% of corticotropinoma
      derived primary cultures, the combined administration of 9-cis RA and Br lowered
      the steady-state level of the ACTH precursor proopiomelanocortin (POMC) more
      efficiently than either of the drugs alone. In conclusion, the effects of a
      combination of 9-cis RA and Br on ACTH synthesis/secretion and cell viability in
      AtT20, and on POMC transcriptional activity in human corticotropinomas might
      represent a suitable starting point for assessing the potential of this treatment
      regimen for ACTH-secreting pituitary adenomas. This study thus has potentially
      important implications for novel therapeutic approaches to CD. 

PMID- 24926821
TI  - The prostate cancer TMPRSS2:ERG fusion synergizes with the vitamin D receptor
      (VDR) to induce CYP24A1 expression-limiting VDR signaling.
AB  - A number of preclinical studies have shown that the activation of the vitamin D
      receptor (VDR) reduces prostate cancer (PCa) cell and tumor growth. The majority
      of human PCas express a transmembrane protease serine 2 (TMPRSS2):erythroblast
      transformation-specific (ETS) fusion gene, but most preclinical studies have been
      performed in PCa models lacking TMPRSS2:ETS in part due to the limited
      availability of model systems expressing endogenous TMPRSS2:ETS. The level of the
      active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3 (1,25D), is
      controlled in part by VDR-dependent induction of cytochrome P450, family 24,
      subfamily 1, polypeptide1 (CYP24A1), which metabolizes 1,25D to an inactive form.
      Because ETS factors can cooperate with VDR to induce rat CYP24A1, we tested
      whether TMPRSS2:ETS would cause aberrant induction of human CYP24A1 limiting the
      activity of VDR. In TMPRSS2:ETS positive VCaP cells, depletion of TMPRSS2:ETS
      substantially reduced 1,25D-mediated CYP24A1 induction. Artificial expression of
      the type VI+72 TMPRSS2:ETS isoform in LNCaP cells synergized with 1,25D to
      greatly increase CYP24A1 expression. Thus, one of the early effects of
      TMPRSS2:ETS in prostate cells is likely a reduction in intracellular 1,25D, which
      may lead to increased proliferation. Next, we tested the net effect of VDR action
      in TMPRSS2:ETS containing PCa tumors in vivo. Unlike previous animal studies
      performed on PCa tumors lacking TMPRSS2:ETS, EB1089 (seocalcitol) (a less
      calcemic analog of 1,25D) did not inhibit the growth of TMPRSS2:ETS containing
      VCaP tumors in vivo, suggesting that the presence of TMPRSS2:ETS may limit the
      growth inhibitory actions of VDR. Our findings suggest that patients with
      TMPRSS2:ETS negative tumors may be more responsive to VDR-mediated growth
      inhibition and that TMPRSS2:ETS status should be considered in future clinical
      trials. 

PMID- 24926822
TI  - ROS are critical for endometrial breakdown via NF-kappaB-COX-2 signaling in a
      female mouse menstrual-like model.
AB  - Progesterone withdrawal triggers endometrial breakdown and shedding during
      menstruation. Menstruation results from inflammatory responses; however, the role
      of reactive oxygen species (ROS) in menstruation remains unclear. In this study,
      we explored the role of ROS in endometrial breakdown and shedding. We found that
      ROS levels were significantly increased before endometrial breakdown in a mouse
      menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and
      endometrial histology examination showed that a broad range of ROS scavengers
      significantly inhibited endometrial breakdown in this model. Furthermore, Western
      blot and immunohistochemical analysis showed that the intracellular translocation
      of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers
      and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was
      decreased by ROS scavengers. Similar changes also occurred in human stromal cells
      in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS,
      hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the
      cytoplasm to the nucleus and increased COX-2 mRNA expression along with
      progesterone maintenance. The nuclear factor kappaB inhibitor MG132 reduced the
      occurrence of these changes in human stromal cells in vitro. Viewed as a whole,
      our results provide evidence that certain ROS are important for endometrial
      breakdown and shedding in a mouse menstrual-like model and function at least
      partially via nuclear factor-kappaB/COX-2 signaling. Similar changes observed in
      human stromal cells could also implicate ROS as important mediators of human
      menstruation. 

PMID- 24926824
TI  - On the time course, generality, and regulation of plasma progesterone release in
      male rats by stress exposure.
AB  - Although progesterone is most commonly regarded in terms of its role in the
      female estrous cycle, reproductive behavior, and pregnancy, progesterone is also
      a precursor to corticosterone (CORT) and is released from the adrenal glands of
      both sexes in response to stress. However, the relationship between plasma CORT
      and progesterone during times of stress has not been well established. To better
      characterize dynamic changes in progesterone release as a result of stressor
      exposure, plasma progesterone levels were measured using enzyme immunoassay under
      multiple conditions, including after stress exposure (footshock, restraint, and
      forced swim), manipulations of the hypothalamic-pituitary-adrenal axis (injection
      of metyrapone or dexamethasone, or adrenalectomy), and in response to CRH and
      ACTH injections. When plasma levels of ACTH, CORT, and progesterone were analyzed
      across studies, CORT and progesterone were found to be highly correlated and
      rarely dissociated. Additionally, it appears that in male rats, the adrenal
      glands are the principle source of circulating progesterone in response to
      stress. Interestingly, a detailed time course indicated lack of a circadian
      rhythm of progesterone secretion, despite a robust rhythm of circulating CORT.
      The current studies provide critical new information on the coincident release of
      progesterone and CORT in response to stress and their somewhat paradoxical
      dissociation across the circadian rhythm. These findings provide an important
      foundation for future studies that will examine the role of stress-induced
      progesterone in behavioral, neuroimmune, and neuroendocrine responses to stress. 

PMID- 24926823
TI  - Large litter rearing improves leptin sensitivity and hypothalamic appetite
      markers in offspring of rat dams fed high-fat diet during pregnancy and
      lactation.
AB  - Maternal high-fat (HF) diet has long-term consequences on the offspring's
      metabolic phenotype. Here, we determined the effects of large litter (LL) rearing
      in offspring of rat dams fed HF diet during gestation and lactation. Pregnant
      Sprague-Dawley rats were maintained on standard chow (CHOW) or HF diet throughout
      gestation and lactation. Pups were raised in normal litters (NLs) (10 pups/dam)
      or LLs (16 pups/dam) during lactation, resulting in 4 groups: CHOW-NL, CHOW-LL,
      HF-NL, and HF-LL. The offspring were weaned onto to either CHOW or HF diet on
      postnatal day 21. Male and female pups with maternal HF diet (HF-NL) had greater
      body weight and adiposity, higher plasma leptin levels, impaired glucose
      tolerance, abnormal hypothalamic leptin signaling pathways (lower leptin receptor
      b [OB-Rb] and signal transducer and activator of transcription 3, higher
      suppressor of cytokine signaling 3 mRNA expression) and appetite markers (lower
      neuropeptide Y and Agouti-related peptide mRNA expression), and reduced phospho
      signal transducer and activator of transcription 3 level in response to leptin in
      the arcuate nucleus at weaning, whereas LL rearing normalized these differences.
      When weaned onto CHOW diet, adult male offspring from HF diet-fed dams continued
      to have greater adiposity, higher leptin levels, and lower hypothalamic OB-Rb,
      and LL rearing improved them. When weaned onto HF diet, both adult male and
      female offspring with maternal HF diet had greater body weight and adiposity,
      higher leptin levels, impaired glucose tolerance, lower OB-Rb, and higher
      suppressor of cytokine signaling 3 in hypothalamus compared with those of CHOW
      dams, whereas LL rearing improved most of them except male OB-Rb expression. Our
      data suggest that LL rearing improves hypothalamic leptin signaling pathways and
      appetite markers in an age- and sex-specific manner in this model. 

PMID- 24926826
TI  - Influence of intention to adhere, beliefs and satisfaction about medicines on
      adherence in solid organ transplant recipients.
AB  - INTRODUCTION: Nonadherence to immunosuppressive (IS) therapy is associated with
      poor outcomes. Identifying factors predicting poor adherence is therefore
      essential. The primary objective of this study was to test whether parameters of
      a model adapted from the theory of planned behavior, and more specifically
      attitudes that are influenced by beliefs and satisfaction with medication, could
      predict adherence in solid organ transplant patients. METHODS: Adherence was
      assessed with a self-reported medication adherence scale and IS blood trough
      concentrations over 6 months, in four transplant units. Satisfaction and beliefs
      were assessed using the Treatment Satisfaction with Medicines Questionnaire
      (SATMED-Q) and Beliefs about Medicines Questionnaire (BMQ), respectively. Theory
      of planned behavior was assessed with a specific questionnaire exploring
      intentions, subjective norms, attitudes and perceived behavioral control.
      Treatment characteristics and socioeconomic data were also collected. RESULTS:
      One hundred and fifty-three solid organ transplant patients were enrolled,
      including lung (n=33), heart (n=43), liver (n=42), and kidney (n=44) patients.
      Satisfaction and positive beliefs about medication were higher in adherent than
      those in nonadherent patients. Factors independently associated with an increased
      risk of nonadherence were negative general beliefs about medications (odds ratio
      [OR]=0.89 [0.83-0.97]), living alone (OR=2.78 [1.09-7.09]), heart transplantation
      (OR=3.49 [1.34-9.09]), and being on everolimus (OR=5.02 [1.21-20.8]). CONCLUSION:
      Negative beliefs toward medications were shown to be an independent risk factor
      of poor adherence. Therefore, the BMQ could be an effective, easy to implement
      tool, for use in everyday practice, to identify patients needing interventions to
      improve adherence to IS.

PMID- 24926825
TI  - Characterization of neural estrogen signaling and neurotrophic changes in the
      accelerated ovarian failure mouse model of menopause.
AB  - Accelerated ovarian failure (AOF) can be induced in young mice with low doses of
      4-vinylcyclohexene diepoxide (VCD), modeling the hormone changes observed across
      menopause. We assessed markers of synaptic plasticity in the hippocampus, anxiety
      like behavior, and spatial learning longitudinally at 4 time points across the
      AOF model: premenopause, early perimenopause, late perimenopause, and
      postmenopause (POST). As others have shown, VCD administration decreased ovarian
      follicle counts and increased acyclicity as the model progressed to POST but with
      no impact on organ or body weights. The morphology of Iba1 immunoreactive
      microglia did not differ between vehicle- and VCD-administered mice. Hippocampal
      postsynaptic density 95 levels were minimally altered across the AOF model but
      decreased at POST in CA3b 24 hours after exogenous estradiol benzoate (EB). In
      contrast, hippocampal phosphorylated AKT levels transiently decreased in
      premenopause but increased at POST after 24 hours of EB in select subregions.
      Electron microscopy revealed fewer estrogen receptor alpha containing dendritic
      spines and terminals in CA1 stratum radiatum at POST. mRNA levels of most brain
      derived neurotrophic factor exons (except V and VI) were lower in POST compared
      with ovariectomized mice. Exon V was sensitive to 24 hours of EB administration
      in POST-VCD. Anxiety-like behavior was unaffected at any menopause phase. Spatial
      learning was unaffected in all groups, but POST-VCD mice performed below chance.
      Our results suggest that the AOF model is suitable for longitudinal studies of
      neurobiological changes across the menopause transition in mice. Our findings
      also point to complex interactions between estrogen receptors and pathways
      involved in synaptic plasticity. 

PMID- 24926827
TI  - How is health economics relevant to transplant clinicians?
AB  - Decision making is complex and difficult in clinical practice. Clinicians are
      often faced with a large range of possible alternative decision options, each
      with their own consequences and trade-offs. Health economics methods enable
      informed decision making on how best to allocate limited resources that could
      lead to most health gains. Economic evaluation in particular is highly relevant
      in transplantation medicine. Transplantation is an expensive intervention, but it
      improves the quality of life and survival of people with chronic diseases. The
      balance between health care resource use and the optimal health gains is useful
      not only to decision-makers, but also to consumers, clinicians, and researchers.
      This article is an overview of the concepts of economic evaluation in the setting
      of transplantation and highlights the applicability of these concepts in clinical
      transplantation.

PMID- 24926828
TI  - Rapamycin represses myotube hypertrophy and preserves viability of C2C12 cells
      during myogenesis in vitro.
AB  - BACKGROUND: Rapamycin (RAPA) has been successfully used for myoblast
      allotransplantation in X chromosome-linked muscular dystrophy mice. However, the
      mechanism of skeletal myogenesis, particularly in starved condition by RAPA,
      remains elusive. For this reason, we investigated the effect of RAPA on C2C12
      myogenesis in serum-starved condition. METHODS: Serum-free treated C2C12 cells
      were mimicked as skeletal myogenesis in nutrition shortage microenvironment. A
      methylthiazoletetrazolium (MTT) assay was used to investigate different RAPA
      concentrations on serum-free treated C2C12 cells and the following assays were
      used to detect the characteristic of C2C12 myogenesis by RAPA in vitro. RESULTS:
      We found that 150 ng/mL of RAPA did not significantly suppress the viability of
      C2C12 differentiated cells by MTT assay. The RAPA concentration could protect
      myoblast serum-starved cells effectively from apoptosis through flow cytometry
      and retain myogenic regulatory factors through quantitative polymerase chain
      reaction analysis. However, RAPA significantly suppressed cell migration in wound
      healing assay (P<0.05). Morphological analyses indicated that RAPA also
      significantly suppressed myotube hypertrophy in serum-starved C2C12 cells.
      Western blot analysis revealed that the ratio of phosphate extracellular signal
      regulated kinase/extracellular signal-regulated kinase and the protein level of p
      Akt decreased in the proliferation medium and in the differentiation medium,
      respectively. CONCLUSION: These findings suggest that myoblast cells are
      sensitive to RAPA under a serum-starved microenvironment. As an immunosuppressive
      agent, RAPA shall be used as a considering dosage and as a safe strategy for
      future myoblast allotransplantation.

PMID- 24926829
TI  - Tolerance: one transplant for life.
AB  - Recently, The Transplantation Society convened a workshop to address the
      question, "What do we need to have in place to make tolerance induction protocols
      a 'standard of care' for organ transplant recipients over the next decade?" In a
      productive 2-day meeting, there was wide-ranging discussion on a broad series of
      topics, resulting in five consensus recommendations as follows: (1) establish a
      registry of results for patients enrolled in tolerance trials; (2) establish
      standardized protocols for sample collection and storage; (3) establish
      standardized biomarkers and assays; (4) include children 12 years and older in
      protocols that have been validated in adults; and (5) establish a task force to
      engage third-party payers in discussions of how to fund tolerance trials. Future
      planned workshops will focus on progress in implementing these recommendations
      and identifying other steps that the community needs to take.

PMID- 24926830
TI  - Therapeutic effects of a non-beta cell bioartificial pancreas in diabetic mice.
AB  - BACKGROUND: Cell-based insulin therapies can potentially improve glycemic
      regulation in insulin-dependent diabetic patients. Enteroendocrine cells
      engineered to secrete recombinant insulin have exhibited glycemic efficacy, but
      have been primarily studied as uncontrollable growth systems in immune
      incompetent mice. Furthermore, reports suggest that suboptimal insulin secretion
      remains a barrier to expanded application. METHODS: Genetic and tissue
      engineering strategies were applied to improve recombinant insulin secretion from
      intestinal L-cells on both a per-cell and per-graft basis. Transduction of
      insulin-expressing GLUTag L-cells with lentivirus carrying an additional human
      insulin gene-enhanced secretion twofold. We infected cells with lentivirus
      expressing a luciferase reporter gene to track cell survival in vivo. To provide
      a growth-controlled and immune protective environment without affecting secretory
      capacity, cells were microencapsulated in barium alginate. Approximately 9*10(7)
      microencapsulated cells were injected intraperitoneally in immune competent
      streptozotocin-induced diabetic mice for therapeutic efficacy evaluation.
      RESULTS: Graft insulin secretion was increased to 16 to 24 mU insulin per day.
      Transient normoglycemia was achieved in treated mice two days after
      transplantation, and endogenous insulin was sufficient to sustain body weights of
      treated mice receiving minimal supplementation. CONCLUSION: Glycemic efficacy of
      a bioartificial pancreas based on insulin-secreting enteroendocrine cells is
      insufficient as a standalone therapy, despite enhancement of graft insulin
      secretion capacity. Supplemental strategies to alleviate secretion limitations
      should be pursued.

PMID- 24926831
TI  - Understanding the influence of ethnicity and socioeconomic factors on graft and
      patient survival after kidney transplantation.
AB  - BACKGROUND: Studies on the influence of socioeconomic factors and ethnicity on
      the results of kidney transplantation have led to various outcomes. In this
      study, we analyzed the influence of a combination of these factors on graft and
      patient survival in a population of kidney transplant recipients. METHODS: This
      retrospective study included all 1,338 patients who received a kidney transplant
      between 2000 and 2011 (825 living, 513 deceased donor transplantations). Both
      clinical and socioeconomic variables were studied. Clinical variables were
      recipient age, gender, ethnicity, original disease, maximum and current panel
      reactive antibodies, ABO blood type, retransplants, pretreatment, time on
      dialysis, comorbidity, transplant year, total number of HLA mismatches, donor
      type (living or deceased), age and gender, and calcineurin inhibitor treatment.
      Each recipient's postal code was linked to a postal code area information
      database to extract information on housing value, income, percentage non
      Europeans in the area, and urbanization level. RESULTS: In multivariable
      analysis, graft survival censored for death was significantly influenced by
      recipient age, maximum panel reactive antibodies, HLA mismatches, donor type,
      donor age, and calcineurin inhibitor treatment. Patient survival was
      significantly influenced by recipient age, comorbidity, transplant year, and
      donor type. Socioeconomic factors and ethnicity did not have a significant
      influence on graft and patient survival. CONCLUSIONS: Though ethnicity and
      socioeconomic factors do not influence survival after kidney transplantation, the
      favorable influence of living donor type is of paramount importance. As non
      Europeans and patients with unfavorable socioeconomic variables less often
      receive a living donor kidney transplant, their survival may be unfavorable after
      all.

PMID- 24926832
TI  - Left ventricular mass changes after renal transplantation: influence of dietary
      sodium and change in serum uric acid.
AB  - BACKGROUND: We hypothesized that dietary sodium may modulate the effect of
      systolic blood pressure and other nonhemodynamic factors, such as high uric acid
      and renal dysfunction, on changes in the left ventricular mass after renal
      transplantation. The objective of the present 3-year follow-up longitudinal study
      was to assess the concomitant influence of these factors on changes in the left
      ventricular mass after renal transplantation. METHODS: Twenty-four-hour urinary
      sodium excretion, glomerular filtration rate (isotopic clearance), and left
      ventricular mass (echocardiography) assessment were done in 165 renal transplant
      patients during the first year and after a follow-up of 3 years after renal
      transplantation. RESULTS: At follow-up, therapy of hypertension was associated
      with normalization of blood pressure in 64% and a decrease in the prevalence of
      left ventricular hypertrophy from 66% to 56%. At baseline and follow-up, systolic
      blood pressure, sodium intake, and serum uric acid emerged as independent and
      significant determinants of the final left ventricular mass index. When the
      population was divided according to sex-specific tertiles of the final 24-hr
      urinary sodium excretion, the relationship between change in serum uric acid
      during follow-up, final left ventricular mass index, and final glomerular
      filtration rate was significant only on the highest tertile of 24-hr urinary
      sodium excretion. CONCLUSION: The decrease in the prevalence of left ventricular
      hypertrophy after renal transplantation is blunted by high sodium intake.
      Persistence of the left ventricular hypertrophy may result from the combined
      adverse influences of excessive dietary sodium intake and increased serum uric
      acid during follow-up despite pharmacological control of blood pressure.

PMID- 24926833
TI  - In memoriam--Carl-Gustav Groth 1933-2014.

PMID- 24926834
TI  - Advantages and disadvantages of conditional systems for characterization of
      essential genes in Toxoplasma gondii.
AB  - The dissection of apicomplexan biology has been highly influenced by the genetic
      tools available for manipulation of parasite DNA. Here, we describe different
      techniques available for the generation of conditional mutants. Comparison of the
      advantages and disadvantages of the three most commonly used regulation systems:
      the tetracycline inducible system, the regulation of protein stability and site
      specific recombination are discussed. Using some previously described examples we
      explore some of the pitfalls involved in gene-function analysis using these
      systems that can lead to wrong or over-interpretation of phenotypes. We will also
      mention different options to standardize the application of these techniques for
      the characterization of gene function in high-throughput.

PMID- 24926835
TI  - Monolithic NPG nanoparticles with large surface area, tunable plasmonics, and
      high-density internal hot-spots.
AB  - Plasmonic metal nanostructures have shown great potential in sensing,
      photovoltaics, imaging and biomedicine, principally due to the enhancement of
      local electric field by light-excited surface plasmons, i.e., collective
      oscillation of conduction band electrons. Thin films of nanoporous gold have
      received a great deal of interest due to the unique 3-dimensional bicontinuous
      nanostructures with high specific surface area. However, in the form of semi
      infinite thin films, nanoporous gold exhibits weak plasmonic extinction and
      little tunability in the plasmon resonance, because the pore size is much smaller
      than the wavelength of light. Here we show that by making nanoporous gold in the
      form of disks of sub-wavelength diameter and sub-100 nm thickness, these
      limitations can be overcome. Nanoporous gold disks not only possess large
      specific surface area but also high-density, internal plasmonic "hot-spots" with
      impressive electric field enhancement, which greatly promotes plasmon-matter
      interactions as evidenced by spectral shifts in the surface plasmon resonance. In
      addition, the plasmonic resonance of nanoporous gold disks can be easily tuned
      from 900 to 1850 nm by changing the disk diameter from 300 to 700 nm.
      Furthermore, nanoporous gold disks can be fabricated as either bound on a surface
      or as non-aggregating colloidal suspension with high stability. 

PMID- 24926836
TI  - Younger age at the time of first metastasis in BRAF-mutated compared to BRAF wild
      type melanoma patients.
AB  - The relationship between BRAF mutations and the patient clinical profile is still
      under question. The objective of the present study was to correlate the BRAF
      mutation status in primary and metastatic melanomas with the clinicopathological
      profile, disease-free (DFS) and overall survival (OS). A total of 367 melanoma
      samples from 278 patients were screened for their BRAF status using a combination
      of allele-specific amplification and DNA sequencing. Two or three tissue samples
      from the same patient were available for 74 patients. The clinicopathological
      characteristics were tested for their association with the BRAF mutation using
      the Fisher's or Pearson's chi2 test. Log-rank tests and Cox models were used for
      survival analyses. BRAF mutation was found in 152 samples (41.4%). Ten of the 74
      patients with several tissue samples (13.5%) had discordant BRAF mutation
      results. BRAF-mutated patients were significantly younger at the time of primary
      melanoma and first diagnosis of metastasis than BRAF wild-type patients but with
      no difference in DFS and OS. According to our results, a primary melanoma with
      BRAF mutation is not associated with a more aggressive illness.

PMID- 24926838
TI  - Role of consultation-liaison psychiatry toward shortening of length of stay for
      medically ill patients with depression.
AB  - Depression in physically ill patients is often encountered in consultation-
      liaison psychiatry. First, this investigation examined the relationship between
      length of stay (LOS) and depression comorbidity. Physically ill patients with
      depression stayed significantly longer than those without. Second, the change of
      LOS with and without antidepressant treatment for depression in medically ill
      patients has been investigated, which showed that LOS in physically ill patients
      with depression could be shortened by effective antidepressant treatment. This
      study also revealed that the early detection and antidepressant treatment are
      important for physically ill patients with depression that could lead to the
      shortening of LOS. 

PMID- 24926839
TI  - Anxiety and mood disorders in primary care practice.
AB  - Anxiety and mood disorders are common conditions in primary health care service.
      Primary care physicians (PCPs) have a privileged role in the early recognition of
      these conditions. In this study, the prevalence rates of threshold and
      subthreshold mood and anxiety disorders were surveyed among 1815 primary care
      attendees in 12 PCPs' offices in Budapest, using the Diagnostic Interview
      Schedule (DIS). The 1-year prevalence of DIS/DSM-III-R anxiety and/or mood
      disorders was 16.8%, and the 1-month prevalence was 12.5%. The occurrence rates
      of subthreshold anxiety and/or depression were 25.7 and 13.1%, respectively. The
      impact of threshold anxiety and mood disorders on work performance was
      considerably higher than the impact of subthreshold symptoms. At the time of the
      interview, 6.7% of the patients received mood and/or anxiety disorder diagnoses
      by their PCPs. The measure of agreement between the diagnoses generated by the
      DIS and the ones given by the PCPs was low. The presence of an acute or chronic
      physical illness made it more difficult for the PCPs to recognize a psychiatric
      disorder. Conversely, patients' psychological complaints significantly improved
      the recognition of anxiety and/or mood disorders. The use of the Beck Depression
      Inventory (BDI) brief version would help the patients to reveal their
      psychological symptoms, and the physicians to recognize an underlying psychiatric
      disorder. 

PMID- 24926840
TI  - Patterns of Axis-II comorbidity in a Turkish OCD sample.
AB  - OBJECTIVE Obsessive-compulsive disorder (OCD) patients frequently present with
      Axis-II disorders, particularly Cluster C (anxiety spectrum) and Cluster A
      (schizophrenic spectrum) personality disorders. The present study examined
      patterns of Axis-II comorbidity in a Turkish OCD sample. In addition, we explored
      the impact of personality disorder symptoms on OCD-symptom severity and symptom
      profile. METHOD Structured psychiatric interviews and self-report measures of OCD
      symptoms and Axis-II disorders were administered to patients with OCD and control
      subjects. RESULTS Patients with OCD obtained significantly higher scores on
      measures of Cluster A and Cluster C personality disorders. Patients with OCD also
      achieved significantly higher scores on the BPD Subscale; however, they did not
      obtain significantly higher scores on other Cluster B subscales. Group
      differences on measures of Cluster A and C disorders were marked. CONCLUSIONS
      Findings are consistent with prior work demonstrating an increased incidence of
      Axis-II disorders among patients with OCD. 

PMID- 24926837
TI  - Involvement of dopamine D2 receptors in addictive-like behaviour for
      acetaldehyde.
AB  - Acetaldehyde, the first metabolite of ethanol, is active in the central nervous
      system, where it exerts motivational properties. Acetaldehyde is able to induce
      drinking behaviour in operant-conflict paradigms that resemble the core features
      of the addictive phenotype: drug-intake acquisition and maintenance, drug
      seeking, relapse and drug use despite negative consequences. Since acetaldehyde
      directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of
      this study was the investigation of dopamine D2-receptors' role in the onset of
      the operant drinking behaviour for acetaldehyde in different functional stages,
      by the administration of two different D2-receptor agonists, quinpirole and
      ropinirole. Our results show that acetaldehyde was able to induce and maintain a
      drug-taking behaviour, displaying an escalation during training, and a
      reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant
      drinking behaviour involved D2-receptor signalling: in particular, quinpirole
      administration at 0.03 mg/kg, induced a significant decrease in the number of
      lever presses both in extinction and in relapse. Ropinirole, administered at 0.03
      mg/kg during extinction, did not produce any modification but, when administered
      during abstinence, induced a strong decrease in acetaldehyde intake in the
      following relapse session. Taken together, our data suggest that acetaldehyde
      exerts its own motivational properties, involving the dopaminergic transmission:
      indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction
      and relapse, negatively affects operant behaviour for acetaldehyde, likely
      decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic
      D2-receptors by ropinirole, during abstinence, decreases the motivation to the
      consecutive reinstatement of acetaldehyde drinking behaviour, likely
      counteracting the reduction in the dopaminergic tone typical of withdrawal. These
      data further strengthen the evidence that acetaldehyde may play a crucial role as
      mediator of ethanol's central effects. 

PMID- 24926841
TI  - Predictors of antidepressant response: A selective review.
AB  - Modern antidepressant drugs have response rates in the 65% range. Considerable
      effort has been made to predict which patients would be more likely to respond to
      antidepressant treatment. Some progress has been made, more in finding
      psychological predictors than biological predictors of antidepressant response.
      In spite of slow progress, these findings have made a valuable contribution
      towards the understanding of antidepressant response. In future it may be
      possible for psychiatrists to use a more broad-based approach, tailoring
      therapies to the clinical profile of individuals. 

PMID- 24926842
TI  - Sexual dysfunction in Saudi depressed male patients.
AB  - INTRODUCTION Sexual dysfunction is common among depressed male patients; however,
      its causes are complex and multifactorial. The aim of this study is to identify
      risk factors for sexual dysfunction associated with depression. METHODS One
      hundred and twenty-five consecutive depressed male patients were interviewed at
      Jeddah Psychiatric Hospital. They were divided in to two groups, on the basis of
      whether they had sexual dysfunction or not. These two groups were then compared
      on a number of potential risk factors, using chi-square and odds ratio. RESULTS
      The majority of patients had not previously been asked about sexual dysfunction.
      Seventy-seven (62%) presented with sexual dysfunction and 48 (38%) without.
      Marital difficulties, hypertension, diabetes, severity of depression and
      tricyclic antidepressants were significant risk factors. No association was found
      with demographic origin, occupation, education or marital status. These results
      are similar in some aspects to those reported in western studies. CONCLUSIONS (a)
      The majority of doctors do not take a sexual history despite its high prevalence.
      (b) Physical illness and overall severity of depression were important risk
      factors. 

PMID- 24926843
TI  - Effects of milnacipran on driving vigilance.
AB  - BACKGROUND Many psychotropic drugs modify sensory and/or psychomotor functions
      involved in car driving and as such they can be a causative factor in road
      accidents. AIM To investigate the effects of the administration of milnacipran, a
      serotonin and noradrenaline dual-action antidepressant, on the sensory and
      psychomotor skills implicated in car driving and to determine any possible
      interactions with the effect of alcohol. METHODS Double-blind, placebo-controlled
      four-sequence cross-over design with 12 healthy volunteers. Laboratory tests
      designed to explore motor responses to auditory and visual stimuli and
      equilibrium on a sensory platform, as well as tests in a real on-road car driving
      situation, were carried out before the drug administration (control) and at the
      end of each sequence. RESULTS There was no significant difference in the results
      of laboratory tests between groups receiving milnacipran compared to placebo. In
      a real driving situation there were no significant effects of milnacipran. In
      addition, milnacipran did not accentuate the negative effects of alcohol.
      CONCLUSIONS Milnacipran, administered at 50 mg b.i.d. to healthy volunteers, does
      not modify the psychomotor skills required for driving. 

PMID- 24926844
TI  - Training health professionals in the recognition, assessement and management of
      suicide risk.
AB  - OBJECTIVES To set up and evaluate a multidisciplinary suicide assessment training
      course for "front-line" clinical staff. METHODS We looked at the impact of two
      types of training courses: full day Workshops with actors role-playing patients;
      and a half-day Lecture. Outcome measures included the Suicide Intervention
      Response Inventory Form 2, a reliable and valid measure of the ability to
      intervene with suicidal clients, and confidence in clinical management scales.
      RESULTS One hundred and seven trainees from different disciplines attended the
      courses. Both types of course led to improvements in the skills and confidence of
      the trainees which were sustained at the two month follow up. CONCLUSION Although
      using actors to role play was more expensive, trainees commented positively on
      their use. The better attendance and feedback at the sessions with actors suggest
      the extra expense involved in using them is worthwhile. We have shown it is
      feasible to run a reasonably inexpensive educational course in a Mental Health
      facility that provides effective training in suicide prevention to a large number
      of trainees. 

PMID- 24926845
TI  - Akathisia treated with olanzapine: Three case reports.
AB  - There have been reports of clozapine being used in the treatment of neuroleptic
      induced akathisia. However, due to clozapine's side effects, its use has been
      limited. Olazapine has been shown to have a similar receptor occupancy to that of
      clozapine and also a similar chemical structure. We present three case histories
      where the commencement of olanzapine has had a dramatic improvement of in the
      symptoms of akathisia induced by other neuroleptics. 

PMID- 24926846
TI  - Recurrent, persisting panic attacks after sudden discontinuation of mirtazapine
      treatment: A case report.
AB  - A 53-year-old woman with depressive symptoms and sleep problems, diagnosed as
      adjustment disorder with depressive reaction (ICD-10, F43.2), was treated with
      mirtazapine at a dose of 30 mg/day for a period of 10 weeks. In view of an
      imminent surgical intervention, the medication was than abruptly stopped. On the
      second day after discontinuation of mirtazapine, the patient developed a typical
      panic attack crisis with symptoms of palpitations, dyspnoea, retro-sternal pain,
      dizziness and nausea, blurred vision, anguish and fear of dying. During the next
      5 days the patient suffered from severe, similar attacks recurring every 1-2 h,
      with each attack lasting about 20 min. Upon hospitalization and minor surgical
      intervention, the frequency and severity of symptoms regressed progressively, but
      the patient remained, with about one attack per week, not symptom free until the
      restitution of mirtazapine treatment at a dose of 30 mg/day. After re
      introduction of mirtazapine panic attacks vanished, and during the entire follow
      up period the patient remained symptom free. This case illustrates the risk of
      abrupt withdrawal of mirtazapine and indicates that, even after a medium-long
      therapy (10 weeks) with mirtazapine, progressive tapering-off of medication is
      advisable. 

PMID- 24926847
TI  - Successful use of intravenous clomipramine in depressive-catatonic state
      associated with corticosteroid treatment.
AB  - We report two female patients who deteriorated to depressive-catatonic state
      after interepisode recovery from a hypomanic episode induced by corticosteroid
      treatment. Their symptoms developed during maintenance treatment with a low dose
      of prednisolone in Case 1 and after discontinuation of betamethasone in Case 2.
      Intravenous clomipramine successfully relieved their symptoms including reduction
      in contact and reactivity, immobility and mutism. These two patients showed no
      schizophrenic symptoms such as hallucinations and delusions. Corticosteroid
      induced mood disorder can deteriorate into depressive stupor, severe depressive
      episode with catatonic features in DSM-IV. Clomipramine, a tricyclic
      antidepressant with relatively stronger serotonin reuptake inhibition, is one of
      the useful treatment options for corticosteroid-induced depression even in severe
      cases. 

PMID- 24926848
TI  - Adaptive sequential testing for multiple comparisons.
AB  - We propose a Markov process theory-based adaptive sequential testing procedure
      for multiple comparisons. The procedure can be used for confirmative trials
      involving multi-comparisons, including dose selection or population enrichment.
      Dose or subpopulation selection and sample size modification can be made at any
      interim analysis. Type I error control is exact. 

PMID- 24926849
TI  - The relationship between direct to consumer advertising (DTCA) and asthma-related
      emergency department use among Medicaid-enrolled children.
AB  - OBJECTIVE: Asthma is a leading cause of emergency department (ED) visits. There
      has been much debate on the impact of direct to consumer advertising (DTCA) on
      healthcare. This study seeks to examine the association between DTCA expenditure
      and asthma-related ED use. STUDY DESIGN: In this study, we combined Medicaid
      administrative data and a national advertising data on asthma medications. The
      sample size consisted of 180,584 Medicaid-enrolled children between the ages of 5
      and 18 years who had an asthma diagnosis. Twenty percent of the Medicaid-enrolled
      children in the sample had asthma-related ED visits. RESULTS: We found that DTCA
      expenditure is associated with a decrease in asthma-related ED visits (OR = 0.75;
      CI: 0.64-0.89). However, at higher levels of DTCA expenditure, the likelihood of
      asthma-related ED visits increases (OR = 1.25; CI: 1.05-1.49), indicating a
      decreased relationship between DTCA and asthma-related ED visits. CONCLUSIONS:
      Our findings suggest that DTCA may be associated with improved health outcomes
      for Medicaid-enrolled children with asthma.

PMID- 24926851
TI  - Biosynthesis of natural products containing beta-amino acids.
AB  - Covering: up to January, 2014. We focus here on beta-amino acids as components of
      complex natural products because the presence of beta-amino acids produces
      structural diversity in natural products and provides characteristic
      architectures beyond those of ordinary alpha-L-amino acids, thus generating
      significant and unique biological functions in nature. In this review, we first
      survey the known bioactive beta-amino acid-containing natural products including
      nonribosomal peptides, macrolactam polyketides, and nucleoside-beta-amino acid
      hybrids. Next, the biosynthetic enzymes that form beta-amino acids from alpha
      amino acids and the de novo synthesis of beta-amino acids are summarized. Then,
      the mechanisms of beta-amino acid incorporation into natural products are
      reviewed. Because it is anticipated that the rational swapping of the beta-amino
      acid moieties with various side chains and stereochemistries by biosynthetic
      engineering should lead to the creation of novel architectures and bioactive
      compounds, the accumulation of knowledge regarding beta-amino acid-containing
      natural product biosynthetic machinery could have a significant impact in this
      field. In addition, genome mining of characteristic beta-amino acid biosynthetic
      genes and unique beta-amino acid incorporation machinery could lead to the
      discovery of new beta-amino acid-containing natural products.

PMID- 24926850
TI  - Growth arrest-specific transcript 5 associated snoRNA levels are related to p53
      expression and DNA damage in colorectal cancer.
AB  - BACKGROUND: The growth arrest-specific transcript 5 gene (GAS5) encodes a long
      noncoding RNA (lncRNA) and hosts a number of small nucleolar RNAs (snoRNAs) that
      have recently been implicated in multiple cellular processes and cancer. Here, we
      investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to
      gain further insight into the potential role of this locus in cell survival and
      oncogenesis both in vivo and in vitro. METHODS: We used quantitative techniques
      to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the
      relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal,
      pre-malignant, and malignant human colorectal tissue and used biological
      techniques to suggest potential roles for these snoRNAs in the DNA damage
      response. RESULTS: GAS5-derived snoRNA expression was induced by DNA damage in a
      p53-dependent manner in colorectal cancer cell lines and their levels were not
      affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived
      snoRNA expression in colorectal tissue. CONCLUSIONS: In aggregate, these data
      suggest that the GAS5-derived snoRNAs are under control of p53 and that they have
      an important role in mediating the p53 response to DNA damage, which may not
      relate to their function in the ribosome. We suggest that these snoRNAs are not
      processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like
      functions, but their precise role requires further evaluation. Furthermore, since
      GAS5 host snoRNAs are often used as endogenous controls in qPCR quantifications
      we show that their use as housekeeping genes in DNA damage experiments can lead
      to inaccurate results.

PMID- 24926852
TI  - Mixing the spacers in azacryptands: effects on halide recognition.
AB  - In this work, we report on two new asymmetric dicopper cryptates, characterized
      by alternate furanyl and p-xylyl spacers. The results of the potentiometric, UV
      vis and X-ray diffraction studies are discussed. In particular, for one of the
      cages in the octaprotonated form, the crystal structure of the complex with
      nitrate is described. From the point of view of the anion binding in water, the
      new dicopper cryptates display stronger similarities to each other than to the
      symmetric analogues (i.e. p-xylyl and furan cryptates). The substitution of even
      only one spacer modifies the distance between the metal ions. This prevents the
      development of the CT band, typically accompanying the binding of halides by the
      furan cryptate, and favors the formation of complexes of different stoichiometry
      with the linear azide anion, not observed for the symmetric cryptates. The
      obtained results may be very helpful in the design of new molecular receptors
      based on dimetallic cryptates, in particular for the tuning of the sensitivity
      towards specific anionic substrates. 

PMID- 24926853
TI  - The nature of chlorine-inhibition of photocatalytic degradation of dichloroacetic
      acid in a TiO2-based microreactor.
AB  - Photocatalytic degradation of dichloroacetic acid (DCA) was studied in a
      continuous-flow set-up using a titanium microreactor with an immobilized double
      layered TiO2 nanoparticle/nanotube film. Chloride ions, formed during the
      degradation process, negatively affect the photocatalytic efficiency and at a
      certain concentration (approximately 0.5 mM) completely stop the reaction in the
      microreactor. Two proposed mechanisms of inhibition with chloride ions,
      competitive adsorption and photogenerated-hole scavenging, have been proposed and
      investigated by adsorption isotherms and electron paramagnetic resonance (EPR)
      measurements. The results show that chloride ions block the DCA adsorption sites
      on the titania surface and reduce the amount of adsorbed DCA molecules. The
      scavenging effect of chloride ions during photocatalysis through the formation of
      chlorine radicals was not detected. 

PMID- 24926854
TI  - Polymorphisms in PDE4D are associated with a risk of COPD in non-emphysematous
      Koreans.
AB  - Despite extensive effort, only a few chronic obstructive pulmonary disease (COPD)
      associated genes have been suggested, indicating that there must be additional
      risk-associated loci. Here we aimed to identify additional COPD-associated SNPs
      and to explore the potential relationship between COPD subgroups and the SNPs in
      the Korean population. We performed a genome-wide association study (GWAS) with
      990 Korean individuals; 102 COPD cases and 544 controls for GWAS using Affymetrix
      SNP array 5.0, and 173 COPD cases and 171 controls for replication. After
      validating the candidate single nucleotide polymorphisms (SNP), we performed
      subgroup analysis by disease phenotype. Through GWAS, we identified a novel SNP
      in the phosphodiesterase-4D (PDE4D) gene [rs16878037 (C>T), p = 1.66 ? 10(-6)]
      that was significantly associated with COPD. This signal in PDE4D was
      successfully replicated in the independent set (p = 0.041). When we combined the
      discovery and replication data, the association signal became more significant (p
      = 5.69 ? 10(-7)). In the COPD subgroup analysis, the T allele of rs16878037 was
      significantly more frequent in COPD patients without severe diffusion capacity
      impairment (mild mixed and obstruction-dominant group) than in patients with
      severe impairment (severe mixed and emphysema-dominant groups). This result
      supports that PDE4D polymorphisms might be involved in the susceptibility to COPD
      especially in non-emphysematous individuals and that they could also affect the
      responsiveness of the PDE4 inhibitor treatment.

PMID- 24926856
TI  - Genetic testing for the susceptibility to alcohol dependence: interest and
      concerns in an African American population.
AB  - BACKGROUND: The search to identify genes for the susceptibility to alcohol
      dependence (AD) is generating interest for genetic risk assessment. The purpose
      of this study is to examine the level of interest and concerns for genetic
      testing for susceptibility to AD. METHODS: Three hundred four African American
      adults were recruited through public advertisement. All participants were
      administered the Genetic Psycho-Social Implication (GPSI) questionnaire, which
      surveyed their interests in hypothetical genetic testing for AD, as well as their
      perception of ethical and legal concerns. RESULTS: Over 85% of participants were
      interested in susceptibility genetic testing; however, persons with higher
      education (p=0.002) and income (p=0.008) were less willing to receive testing.
      Perception of AD as a deadly disease (48.60%) and wanting to know for their
      children (47.90%) were the strongest reasons for interest in testing. Among those
      not interested in testing, the belief that they were currently acting to lower
      their risk was the most prevalent. The most widely expressed concern in the
      entire sample was the accuracy of testing (35.50%). Other notable concerns, such
      as issues with the method of testing, side effects of venipuncture, falsely
      reassuring results, and lack of guidelines on "what to do next" following test
      results, were significantly associated with willingness to receive testing.
      CONCLUSION: Although an overwhelming majority of participants expressed an
      interest in genetic testing for AD, there is an understandable high level of
      methodological and ethical concerns. Such information should form the basis of
      policies to guide future genetic testing of AD.

PMID- 24926857
TI  - Apoptotic death of prostate cancer cells by a gonadotropin-releasing hormone-II
      antagonist.
AB  - Gonadotropin-releasing hormone-I (GnRH-I) has attracted strong attention as a
      hormonal therapeutic tool, particularly for androgen-dependent prostate cancer
      patients. However, the androgen-independency of the cancer in advanced stages has
      spurred researchers to look for new medical treatments. In previous reports, we
      developed the GnRH-II antagonist Trp-1 to inhibit proliferation and stimulate the
      autophagic death of various prostate cancer cells, including androgen-independent
      cells. We further screened many GnRH-II antagonists to identify molecules with
      higher efficiency. Here, we investigated the effect of SN09-2 on the growth of
      PC3 prostate cancer cells. SN09-2 reduced the growth of prostate cancer cells but
      had no effect on cells derived from other tissues. Compared with Trp-1, SN09-2
      conspicuously inhibited prostate cancer cell growth, even at low concentrations.
      SN09-2-induced PC3 cell growth inhibition was associated with decreased membrane
      potential in mitochondria where the antagonist was accumulated, and increased
      mitochondrial and cytosolic reactive oxygen species. SN09-2 induced lactate
      dehydrogenase release into the media and annexin V-staining on the PC3 cell
      surface, suggesting that the antagonist stimulated prostate cancer cell death by
      activating apoptotic signaling pathways. Furthermore, cytochrome c release from
      mitochondria to the cytosol and caspase-3 activation occurred in a concentration-
      and time-dependent manner. SN09-2 also inhibited the growth of PC3 cells
      xenotransplanted into nude mice. These results demonstrate that SN09-2 directly
      induces mitochondrial dysfunction and the consequent ROS generation, leading to
      not only growth inhibition but also apoptosis of prostate cancer cells. 

PMID- 24926858
TI  - An examination of the relationship between hotspots and recombination associated
      with chromosome 21 nondisjunction.
AB  - Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy
      among live-born infants and is caused mainly by nondisjunction of chromosome 21
      within oocytes. Risk factors for nondisjunction depend on the parental origin and
      type of meiotic error. For errors in the oocyte, increased maternal age and
      altered patterns of recombination are highly associated with nondisjunction.
      Studies of normal meiotic events in humans have shown that recombination clusters
      in regions referred to as hotspots. In addition, GC content, CpG fraction,
      Poly(A)/Poly(T) fraction and gene density have been found to be significant
      predictors of the placement of sex-averaged recombination in the human genome.
      These observations led us to ask whether the altered patterns of recombination
      associated with maternal nondisjunction of chromosome 21 could be explained by
      differences in the relationship between recombination placement and recombination
      related genomic features (i.e., GC content, CpG fraction, Poly(A)/Poly(T)
      fraction or gene density) on 21q or differential hot-spot usage along the
      nondisjoined chromosome 21. We found several significant associations between our
      genomic features of interest and recombination, interestingly, these results were
      not consistent among recombination types (single and double proximal or distal
      events). We also found statistically significant relationships between the
      frequency of hotspots and the distribution of recombination along nondisjoined
      chromosomes. Collectively, these findings suggest that factors that affect the
      accessibility of a specific chromosome region to recombination may be altered in
      at least a proportion of oocytes with MI and MII errors. 

PMID- 24926859
TI  - Illustrating consistency of different experimental approaches to probe the buried
      polymer/metal interface using sum frequency generation vibrational spectroscopy.
AB  - In this paper, we demonstrate our ability to directly probe the molecular
      structures of the buried polymer/metal interface using sum frequency generation
      (SFG) vibrational spectroscopy. Spectroscopic data from different experimental
      approaches were compared and analyzed to deduce the molecular ordering
      information at a buried polymer/metal interface, i.e. the poly(n-butyl
      methylacrylate) (PBMA)/silver (Ag) interface. Solid spectroscopic evidence
      suggested that we successfully detected the molecular vibrational signals
      generated from the buried PBMA/Ag interface. It was found that the side butyl
      methyl groups at the PBMA/Ag interface are polar-ordered and have different
      orientational ordering from those at the PBMA surface in air. We believe that
      this study will provide a useful experimental and analytical framework for the
      SFG spectroscopy to probe the buried polymer/metal interfaces in the future. 

PMID- 24926860
TI  - Effects of sample treatments on genome recovery via single-cell genomics.
AB  - Single-cell genomics is a powerful tool for accessing genetic information from
      uncultivated microorganisms. Methods of handling samples before single-cell
      genomic amplification may affect the quality of the genomes obtained. Using three
      bacterial strains we show that, compared to cryopreservation, lower-quality
      single-cell genomes are recovered when the sample is preserved in ethanol or if
      the sample undergoes fluorescence in situ hybridization, while sample
      preservation in paraformaldehyde renders it completely unsuitable for sequencing.

PMID- 24926861
TI  - From community approaches to single-cell genomics: the discovery of ubiquitous
      hyperhalophilic Bacteroidetes generalists.
AB  - The microbiota of multi-pond solar salterns around the world has been analyzed
      using a variety of culture-dependent and molecular techniques. However, studies
      addressing the dynamic nature of these systems are very scarce. Here we have
      characterized the temporal variation during 1 year of the microbiota of five
      ponds with increasing salinity (from 18% to >40%), by means of CARD-FISH and
      DGGE. Microbial community structure was statistically correlated with several
      environmental parameters, including ionic composition and meteorological factors,
      indicating that the microbial community was dynamic as specific phylotypes
      appeared only at certain times of the year. In addition to total salinity,
      microbial composition was strongly influenced by temperature and specific ionic
      composition. Remarkably, DGGE analyses unveiled the presence of most phylotypes
      previously detected in hypersaline systems using metagenomics and other molecular
      techniques, such as the very abundant Haloquadratum and Salinibacter
      representatives or the recently described low GC Actinobacteria and
      Nanohaloarchaeota. In addition, an uncultured group of Bacteroidetes was present
      along the whole range of salinity. Database searches indicated a previously
      unrecognized widespread distribution of this phylotype. Single-cell genome
      analysis of five members of this group suggested a set of metabolic
      characteristics that could provide competitive advantages in hypersaline
      environments, such as polymer degradation capabilities, the presence of retinal
      binding light-activated proton pumps and arsenate reduction potential. In
      addition, the fairly high metagenomic fragment recruitment obtained for these
      single cells in both the intermediate and hypersaline ponds further confirm the
      DGGE data and point to the generalist lifestyle of this new Bacteroidetes group. 

PMID- 24926863
TI  - Highly efficient exciplex formation via radical ion pair recombination in X
      irradiated alkane solutions for luminophores with short fluorescence lifetimes.
AB  - X-irradiation of alkane solutions of N,N-dimethylaniline with various organic
      luminophores produces characteristic emission bands ascribed to the corresponding
      exciplexes. In contrast to optical generation, which requires diffusion
      controlled quenching of excited states, an additional channel of exciplex
      formation via irreversible recombination of radical ion pairs is operative here,
      which produces exciplexes in solution with high efficiency even for p-terphenyl
      and diphenylacetylene having fluorescence decay times of 0.95 ns and 8 ps,
      respectively. The exciplex emission band is sensitive to an external magnetic
      field and exerts a very large observed magnetic field effect of up to 20%, the
      maximum possible value under the conditions of the described experiment. 

PMID- 24926862
TI  - Biodiversity acts as insurance of productivity of bacterial communities under
      abiotic perturbations.
AB  - Anthropogenic disturbances are detrimental to the functioning and stability of
      natural ecosystems. Critical ecosystem processes driven by microbial communities
      are subjected to these disturbances. Here, we examine the stabilizing role of
      bacterial diversity on community biomass in the presence of abiotic perturbations
      such as addition of heavy metals, NaCl and warming. Bacterial communities with a
      diversity gradient of 1-12 species were subjected to the different treatments,
      and community biomass (OD600) was measured after 24 h. We found that initial
      species richness and phylogenetic structure impact the biomass of communities.
      Under abiotic perturbations, the presence of tolerant species in community
      largely contributed in community biomass production. Bacterial diversity
      stabilized the biomass across the treatments, and differential response of
      bacterial species to different perturbations was the key reason behind these
      effects. The results suggest that biodiversity is crucial for maintaining the
      stability of ecosystem functioning and acts as ecological insurance under abiotic
      perturbations. Biodiversity in natural ecosystems may also uphold the ecosystem
      functioning under anthropogenic disturbance.

PMID- 24926865
TI  - OCD: Towards DSM-V.

PMID- 24926864
TI  - First molecular characterization of a Hepatozoon species (Apicomplexa:
      Hepatozoidae) infecting birds and description of a new species infecting storm
      petrels (Aves: Hydrobatidae).
AB  - During a survey of blood parasites in a population of Leach's and black storm
      petrels ( Oceanodroma leucorhoa and Oceanodroma melania) in Mexico, infection by
      a Hepatozoon species in erythrocytes of several birds was noted. Here we describe
      the species as Hepatozoon peircei sp. nov. Some species of Hepatozoon described
      from birds have been identified as lankesterellids when DNA molecular analyses
      were conducted. However, a sequence of 1,774 bp of the parasite found infecting
      storm petrels in this study clearly show the parasite is a species of the genus
      Hepatozoon. This is the first Hepatozoon species infecting birds to be
      characterized at the molecular level and the first found infecting erythrocytes
      and not leucocytes.

PMID- 24926866
TI  - Anxiety and OC spectrum disorders over life cycle.
AB  - The developmental trajectory of anxiety disorders over the life span is an area
      of increasing interest. Obsessive-compulsive disorder (OCD), traditionally
      considered an anxiety disorder, is a disabling and chronic condition that is
      associated with considerable negative impact on numerous aspects of daily
      functioning. Lifetime prevalence has been estimated at 1.6%. OCD, like other
      anxiety disorders, is frequently associated with comorbid depression. Unlike
      depression, anxiety disorders begin early in life, often early in the teenage
      years. Thus, the total duration of symptoms may be nearly lifelong. Although a
      variety of pharmacological and behavioral treatments have proven effective, many
      patients fail to respond, and for some of those who do respond, response may be
      incomplete. Patients with these disorders deserve early and rigorous treatment,
      but the best way of achieving this goal is unclear. The Cape Town Consensus
      Statement reflects the opinions of an international expert working group who
      convened to review what is known about OCD and to suggest directions for future
      research. In their view, phenomenonological, clinical, and neurobiological
      features of OCD do not justify continued placement in the category of anxiety
      disorders. It has been suggested that OCD might better be placed in a separate
      category of obsessive-compulsive related disorders (OCRDs). Phenomenology,
      demographics, epidemiology, course of illness, comorbidity, endophenotyping and
      treatment response are factors that may influence the definition of the
      boundaries and relationships between these disorders. Endophenotyping
      characteristics include brain circuitry, neurocognitive factors, genetics, and
      immune function. Incorporation of a dimensional approach to the existing
      categorical approach to diagnosis may help to enrich the diagnostic specificity
      of the approach to OC behaviors. 

PMID- 24926867
TI  - The Cape Town Consensus Statement on obsessive-compulsive disorder.
AB  - The Cape Town Consensus Statement provides an up-to-date summary of the
      literature and clinical recommendations for healthcare professionals with regard
      to the currently available scientific data relating to the symptomatology,
      diagnosis, neurobiology and treatment of obsessive-compulsive disorder (OCD).
      This review outlines some of these issues covered by the Consensus Statement.
      Current differing classifications of OCD do not take the same approach to
      conceptualizing this condition. There is biological and clinical evidence to
      suggest that OCD should be classified separately from anxiety disorders and the
      next revision of current nosology may be more consistent with our understanding
      of the psychobiology of OCD. Indeed, the psychobiological basis of some OCD
      subtypes such as early-onset OCD, and OCD spectrum disorders such as Tourette's
      syndrome, is increasingly understood. Serotonin selective reuptake inhibitors
      (SSRIs) and cognitive behavioral therapy (CBT) are the treatments of choice for
      children and adults with OCD and several OCD spectrum disorders, although gaps in
      our knowledge regarding treatment remain. 

PMID- 24926868
TI  - The importance of serotonin and noradrenaline in anxiety.
AB  - The therapeutics of obsessive-compulsive disorder (OCD) involves the serotonergic
      system in the brain; the selective serotonin reuptake inhibitors (SSRIs) are the
      only class of drugs to be consistently effective for this disorder. Preclinical
      studies in the orbito-frontal cortex - a brain area known to be involved in
      mediation of OCD symptoms - show that sustained administration of SSRI for 2
      months leads to enhanced 5-HT release. Initially, raised 5-HT levels, resulting
      from serotonin (5-HT) reuptake inhibition, over-activates the cell body 5-HT1A
      autoreceptor, which has an inhibitory effect on the neuronal firing rate.
      However, after long-term administration of SSRIs, these 5-HT1A autoreceptors
      become desensitized to the raised extracellular 5-HT levels, and increase 5-HT
      transmission. The recovery of neuronal firing rate is faster with escitalopram
      (the active S-enantiomer of citalopram) than with citalopram, which may be due to
      different mechanisms of action. The 5-HT system has reciprocal interactions with
      the noradrenaline (NA) system. Although not a major mediator in the treatment of
      OCD symptomatology, patients with anxiety disorders such as panic disorder have
      increased NA reactivity and/or tone. Long-term SSRI administration reduces the
      firing rate of NA neurones, unlike 5-HT neurones. Evidence indicates that accrued
      5-HT levels have an inhibitory modulatory effect on NA transmission, thus
      indicating the clinical relevance of SSRI treatment for anxiety disorders. The
      different effectiveness of the SSRIs escitalopram and citalopram in enhancing
      synaptic 5-HT levels may be due to the inhibitory action of the R-enantiomer in
      racemic citalopram on S-enantiomer binding to the 5-HT transporter. This allows
      escitalopram to produce higher extracellular 5-HT levels than can be achieved by
      the equivalent S-enantiomer dose of citalopram. Escitalopram is therefore a
      viable front-line treatment option for people with anxiety disorders, and
      possibly for those who have failed to respond to conventional SSRI therapies. 

PMID- 24926869
TI  - New treatment options for OCD.
AB  - Pharmacological management of obsessive-compulsive disorder (OCD) is achieved
      using drugs that inhibit the synaptic uptake of serotonin, such as clomipramine,
      a tricyclic antidepressant, and the selective serotonin reuptake inhibitors
      (SSRIs). Recent studies suggest that the improved tolerability profile of the
      SSRIs relative to clomipramine may offer a more suitable treatment choice.
      Escitalopram, the therapeutically active S-enantiomer of citalopram, is the most
      selective SSRI currently available. In a 24-week randomized, placebo-controlled,
      double-blind study, escitalopram (20 mg) was associated with significantly lower
      symptom scores at 12 weeks (P<0.01) and increased response rate (Yale-Brown
      Obsessive-compulsive Scale [Y-BOCS]) (70.2%) compared with placebo (50.4%).
      Escitalopram (10 mg) was more effective in reducing symptom scores than placebo
      at 24 weeks (P=0.052). Escitalopram 20 mg was also associated with improved
      remitter status (Y-BOCS total score <=10) compared with paroxetine (40 mg) or
      placebo from week 12. In a relapse-prevention study, 10 and 20 mg escitalopram
      showed a statistically significant superior effect relative to placebo on time to
      relapse of OCD with a hazard ratio of 2.74. Escitalopram was well-tolerated by
      patients with OCD. In conclusion, escitalopram provides significant symptom
      relief and prevention of relapse during long-term use and deserves consideration
      as a first-line agent in the long-term pharmacotherapy of OCD. 

PMID- 24926870
TI  - Evidence base on outpatient behavioral treatments for adolescent substance use:
      updates and recommendations 2007-2013.
AB  - This article updates the evidence base on outpatient behavioral treatments for
      adolescent substance use (ASU) since publication of the previous review completed
      for this journal by Waldron and Turner ( 2008 ). It first summarizes the Waldron
      and Turner findings as well as those from more recent literature reviews and meta
      analytic studies of ASU treatment. It then presents study design and methods
      criteria used to select 19 comparative studies subjected to Journal of Clinical
      Child & Adolescent Psychology level of support evaluation. These 19 studies are
      grouped by study category (efficacy or effectiveness) and described for sample
      characteristics, methodological quality, and substance use outcomes. Cumulative
      level of support designations are then made for each identified treatment
      approach: ecological family-based treatment, group cognitive-behavioral therapy,
      and individual cognitive-behavioral therapy are deemed Well Established;
      behavioral family-based treatment and motivational interviewing are deemed
      Probably Efficacious; drug counseling is deemed Possibly Efficacious; and four
      integrated treatment models combining more than one approach are deemed Well
      Established or Probably Efficacious. The remainder of the article (a) articulates
      fidelity, mediator, and moderator effects reported for evidence-based approaches
      since 2008 and (b) recommends four enhancements to the prevailing business model
      of ASU outpatient services to accelerate penetration of evidence-based approaches
      into the underserved consumer base: pursue partnerships with influential
      governmental systems, utilize web-based technology to extend reach and control
      costs, adapt effective methods for linking services across sectors of care, and
      promote uptake and sustainability by emphasizing return on investment. 

PMID- 24926871
TI  - Lymph fasciocutaneous lateral thoracic artery flap: anatomical study and clinical
      use.
AB  - BACKGROUND:  The lateral thoracic flap was first studied in the mid-1970s but its
      use has been limited because of pedicle anatomical variations. However, after the
      development of lymph node transfer surgery, the axilla/upper lateral thorax
      presented as a promising donor area. Through a detailed anatomical study, the
      lateral thoracic flap was evaluated regarding its vascularization and
      composition. Later, it was used for pedicle and free flap reconstructions.
      METHODS:  A total of 40 flaps were dissected in fresh cadavers and the
      characteristics of the lateral thoracic pedicle and its relationship to the upper
      lateral thoracic axillary lymph nodes (LTLN) were analyzed. We performed six
      pedicle flap reconstructions around the shoulder area and a free lymph node
      transfer for lower limb lymphedema. RESULTS:  In the cadaveric dissections, the
      lateral thoracic pedicle branched off the axillary vessels and was found to be a
      primary level I axillary lymph node irrigator before reaching the skin. The
      cutaneous portion of the artery was present in 87.5% of the dissections. Arterial
      caliber was an average of 1.3 and venous, 2.6 mm. Five to seven lymph nodes were
      isolated with each pedicle and a lymph fasciocutaneous flap could be designed. In
      seven clinical cases, all of the flaps survived. Functioning lymph nodes were
      visualized on lymphoscintigraphy after their transfer to the ankle. Donor area
      had an inconspicuous evolution. CONCLUSION:  Lateral thoracic flap is a feasible
      flap with low donor area morbidity in a concealed region that can be harvested
      with upper LTLN for transplantation.

PMID- 24926873
TI  - Influence of vegetation restoration on topsoil organic carbon in a small
      catchment of the loess hilly region, China.
AB  - Understanding effects of land-use changes driven by the implementation of the
      "Grain for Green" project and the corresponding changes in soil organic carbon
      (SOC) storage is important in evaluating the environmental benefits of this
      ecological restoration project. The goals of this study were to quantify the
      current soil organic carbon density (SOCD) in different land-use types
      [cultivated land, abandoned land (cessation of farming), woodland, wild grassland
      and orchards] in a catchment of the loess hilly and gully region of China to
      evaluate the benefits of SOC sequestration achieved by vegetation restoration in
      the past 10 years as well as to discuss uncertain factors affecting future SOC
      sequestration. Based on soil surveys (N = 83) and laboratory analyses, the
      results show that the topsoil (0-20 cm) SOCD was 20.44 Mg/ha in this catchment.
      Using the SOCD in cultivated lands (19.08 Mg/ha) as a reference, the SOCD in
      woodlands and abandoned lands was significantly higher by 33.81% and 8.49%,
      respectively, whereas in orchards, it was lower by 10.80%. The correlation
      analysis showed that SOC and total nitrogen (TN) were strongly correlated (R2 =
      0.98) and that the average C?N (SOC?TN) ratio was 9.69. With increasing years
      since planting, the SOCD in woodlands showed a tendency to increase; however, no
      obvious difference was observed in orchards. A high positive correlation was
      found between SOCD and elevation (R2 = 0.395), but a low positive correlation was
      found between slope and SOCD (R2 = 0.170, P = 0.127). In the past 10 years of
      restoration, SOC storage did not increase significantly (2.74% or 3706.46 t) in
      the catchment where the conversion of cultivated land to orchards was the primary
      restoration pattern. However, the potential contribution of vegetation
      restoration to SOC sequestration in the next several decades would be massive if
      the woodland converted from the cropland is well managed and maintained. 

PMID- 24926874
TI  - Characteristics of mesenchymal stem cells originating from the bilateral inferior
      turbinate in humans with nasal septal deviation.
AB  - BACKGROUND AND OBJECTIVES: Nasal septal deviation (NSD) is often associated with
      overgrowth of the unilateral inferior turbinate. In vivo and in vitro studies
      indicate that human mesenchymal stem cells (MSCs) are able to differentiate into
      multiple cell types, including osteoblasts. We tested the hypothesis that
      turbinate size affects human turbinate-derived MSC (hTMSCs) quantity,
      proliferation, and differentiation into osteogenic lineages, and that
      hypertrophic turbinates may predispose to NSD on the contralateral side. SUBJECTS
      AND METHODS: The hypertrophic and contralateral inferior turbinate tissues used
      in our study were obtained and cultured from the tissue discarded from 10
      patients who underwent septoplasty and partial turbinectomy. After isolating the
      hTMSCs from both turbinates, the cells were enumerated using an automated cell
      counter. The expression of surface markers for MSCs over four passages was
      assessed by fluorescent-activated cell sorting analysis (FACS), and cell
      proliferation was assessed using a cell counting kit (CCK)-8 according to
      turbinate size. In addition, osteogenic differentiation of hTMSCs was identified
      using alkaline phosphatase (ALP) and alizarin red S staining, after which
      osteoblastic gene expression was evaluated. RESULTS: There was no significant
      difference in the number of hTMSCs. FACS analysis revealed that the hTMSCs were
      negative for CD14, CD19, CD34, and HLA-DR, and positive for CD29, CD73, and CD90,
      representing a characteristic MSC phenotype, with no significant difference
      between the two groups. The cellular proliferation and osteogenic differentiation
      potential of the hTMSCs were also not significantly different between the two
      groups. CONCLUSIONS: We conclude that turbinate size does not affect the
      characterization, proliferation, and osteogenic differentiation potential of
      hTMSCs in vitro test, and therefore should not affect the clinical decision of
      whether to use autologous or allogenic hTMSCs. However, more experiments are
      required to definitively state the relationship of hTMSCs with turbinate size or
      the process NSD in humans.

PMID- 24926875
TI  - Bovine collagen peptides compounds promote the proliferation and differentiation
      of MC3T3-E1 pre-osteoblasts.
AB  - OBJECTIVE: Collagen peptides (CP) compounds, as bone health supplements, are
      known to play a role in the treatment of osteoporosis. However, the molecular
      mechanisms of this process remain unclear. This study aimed to investigate the
      effects of bovine CP compounds on the proliferation and differentiation of MC3T3
      E1 cells. METHODS: Mouse pre-osteoblast cell line MC3T3-E1 subclone 4 cells were
      treated with bovine CP compounds. Cell proliferation was analyzed by MTT assays
      and the cell cycle was evaluated by flow cytometry scanning. Furthermore, MC3T3
      E1 cell differentiation was analyzed at the RNA level by real-time PCR and at the
      protein level by western blot analysis for runt-related transcription factor 2
      (Runx2), a colorimetric p-nitrophenyl phosphate assay for alkaline phosphatase
      (ALP), and ELISA for osteocalcin (OC). Finally, alizarin red staining for
      mineralization was measured using Image Software Pro Plus 6.0. RESULTS: Cell
      proliferation was very efficient after treatment with different concentrations of
      bovine CP compounds, and the best concentration was 3 mg/mL. Bovine CP compounds
      significantly increased the percentage of MC3T3-E1 cells in G2/S phase. Runx2
      expression, ALP activity, and OC production were significantly increased after
      treatment with bovine CP compounds for 7 or 14 days. Quantitative analyses with
      alizarin red staining showed significantly increased mineralization of MC3T3-E1
      cells after treatment with bovine CP compounds for 14 or 21 days. CONCLUSIONS:
      Bovine CP compounds increased osteoblast proliferation, and played positive roles
      in osteoblast differentiation and mineralized bone matrix formation. Taking all
      the experiments together, our study indicates a molecular mechanism for the
      potential treatment of osteoarthritis and osteoporosis.

PMID- 24926876
TI  - Organizational factors and long-term mortality after hip fracture surgery. A
      cohort study of 6143 consecutive patients undergoing hip fracture surgery.
AB  - OBJECTIVE: In hospital and health care organizational factors may be changed to
      reduce postoperative mortality. The aim of this study is to evaluate a possible
      association between mortality and 'length of hospital stay', 'priority of
      surgery', 'time of surgery', or 'surgical delay' in hip fracture surgery. DESIGN:
      Observational cohort study. SETTING: Prospectively and consecutively reported
      data from the Danish Anaesthesia Database were linked to The Danish National
      Registry of Patients and The Civil Registration System. Records on vital status,
      admittance, discharges, codes of diagnosis, anaesthetic and surgical procedures
      were retrieved. PARTICIPANTS: 6143 patients aged more than 65 years undergoing
      hip fracture surgery. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: The
      one year mortality was 30% (28-31%, 95% Confidence interval (CI)). In a
      multivariate model 'length of hospital stay' less than 10 days and more than 20
      days are associated with mortality with hazard ratios of 1.34 (1.20-1.53 CI,
      p<0.001) and 1.27 (1.06-1.51 CI, p<0.001), respectively. 'Priority of surgery'
      categorized as 'non-scheduled' is associated with mortality with a hazard ratio
      of 1.31 (1.13-1.50 CI, p<0.001). Surgical delay and time of surgery are not
      significantly associated with mortality. CONCLUSION: Non-scheduled surgery and
      length of hospital stay were associated with increased mortality. Confounding by
      indication may bias observational studies evaluating early and late discharge as
      well as priority; therefore cluster randomized clinical trials comparing
      different clinical set ups may be warranted evaluating health care organizational
      factors.

PMID- 24926877
TI  - The effect of silver nanoparticles on seasonal change in arctic tundra bacterial
      and fungal assemblages.
AB  - The impact of silver nanoparticles (NPs) and microparticles (MPs) on bacterial
      and fungal assemblages was studied in soils collected from a low arctic site. Two
      different concentrations (0.066% and 6.6%) of Ag NPs and Ag MPs were tested in
      microcosms that were exposed to temperatures mimicking a winter to summer
      transition. Toxicity was monitored by differential respiration, phospholipid
      fatty acid analysis, polymerase chain reaction-denaturing gradient gel
      electrophoresis and DNA sequencing. Notwithstanding the effect of Ag MPs,
      nanosilver had an obvious, additional impact on the microbial community,
      underscoring the importance of particle size in toxicity. This impact was
      evidenced by levels of differential respiration in 0.066% Ag NP-treated soil that
      were only half that of control soils, a decrease in signature bacterial fatty
      acids, and changes in both richness and evenness in bacterial and fungal DNA
      sequence assemblages. Prominent after Ag NP-treatment were Hypocreales fungi,
      which increased to 70%, from only 1% of fungal sequences under control
      conditions. Genera within this Order known for their antioxidant properties
      (Cordyceps/Isaria) dominated the fungal assemblage after NP addition. In
      contrast, sequences attributed to the nitrogen-fixing Rhizobiales bacteria
      appeared vulnerable to Ag NP-mediated toxicity. This combination of
      physiological, biochemical and molecular studies clearly demonstrate that Ag NPs
      can severely disrupt the natural seasonal progression of tundra assemblages. 

PMID- 24926878
TI  - Nucleosomal histone proteins of L. donovani: a combination of recombinant H2A,
      H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic
      efficacy against Leishmania challenge in hamsters.
AB  - The present study includes cloning and expression of recombinant Leishmania
      donovani histone proteins (rLdH2B, rLdH3, rLdH2A and rLdH4), assessment of their
      immunogenicity in Leishmania infected cured patients/endemic contacts as well as
      in cured hamsters and finally evaluation of their prophylactic efficacy in
      hamsters against L. donovani challenge. All recombinant proteins were expressed
      and purified from the heterologous bacterial host system. Leishmania infected
      cured patients/endemic contacts as well as cured hamsters exhibited significantly
      higher proliferative responses to individual recombinant histones and their
      pooled combination (rLdH2B+rLdH3+rLdH2A+rLdH4) than those of L.donovani infected
      hosts. The L.donovani soluble antigens (SLD) stimulated PBMCs of cured/exposed
      and Leishmania patients to produce a mixed Thl/Th2-type cytokine profile, whereas
      rLdH2B, rLdH3, rLdH2A, rLdH4 and pooled combination (rLdH2-4) stimulated the
      production of Th1 cytokines IFN-gamma, IL-12 and TNF-alpha but not Th2 cytokines
      IL-4 or IL-10. The immunogenicity of these histone proteins along with their
      combination was also checked in cured hamsters where they stimulated higher
      lymphoproliferation and Nitric oxide production in lymphocytes of cured hamsters
      than that of infected controls. Moreover, significantly increased IgG2 response,
      an indicative of cell mediated immunity, was observed in cured hamsters against
      these individual proteins and their combination as compared to infected hamsters.
      Further, it was demonstrated that rLdH2B, rLdH3, rLdH2A and rLdH4 and pooled
      combination were able to provide considerable protection for hamsters against L.
      donovani challenge. The efficacy was supported by the increased inducible Nitric
      Oxide Synthase (iNOS) mRNA transcripts and Th1-type cytokines--IFN-gamma, IL-12
      and TNF-alpha and down-regulation of IL-4, IL-10 and TGF-beta. Hence, it is
      inferred that pooled rLdH2-4 elicits Thl-type of immune responses exclusively and
      confer considerable protection against experimental Visceral Leishmaniasis.

PMID- 24926879
TI  - Self-sterility in Camellia oleifera may be due to the prezygotic late-acting self
      incompatibility.
AB  - In this report, self-sterility in Camellia oleifera was explored by comparing
      structural and statistical characteristics following self-pollination (SP) and
      cross-pollination (CP). Although slightly delayed pollen germination and pollen
      tube growth in selfed ovaries compared to crossed ovaries was observed, there was
      no significant difference in the percentages of pollen that germinated and pollen
      tubes that grew to the base of the style. There was also no difference in
      morphological structure after the two pollination treatments. However, the
      proportions of ovule penetration and double fertilization in selfed ovules were
      significantly lower than in crossed ovules, indicating that a prezygotic late
      acting self-incompatible mechanism may exist in C. oleifera. Callose deposition
      was observed in selfed abortive ovules, but not in normal. Ovules did not show
      differences in anatomic structure during embryonic development, whereas
      significant differences were observed in the final fruit and seed set. In
      addition, aborted ovules in selfed ovaries occurred within 35 days after SP and
      prior to zygote division. However, this process did not occur continuously
      throughout the life cycle, and no zygotes were observed in the selfed abortive
      ovules. These results indicated that the self-sterility in C. oleifera may be
      caused by prezygotic late-acting self-incompatibility (LSI). 

PMID- 24926880
TI  - Characterization of side population cells isolated from the colon cancer cell
      line SW480.
AB  - Side population (SP) cells may play a crucial role in tumorigenesis and the
      recurrence of cancer. Many types of cell lines and tissues have demonstrated the
      presence of SP cells, including colon cancer cell lines. This study aimed to
      identify cancer stem cells (CSCs) in the SP of the colon cancer cell line SW480.
      SP cells were isolated by fluorescence-activated cell sorting (FACS), followed by
      serum-free medium (SFM) culture. The self-renewal, differentiated progeny, clone
      formation, proliferation, invasion ability, cell cycle, chemosensitivity and
      tumorigenic properties in SP and non-SP (NSP) cells were investigated through in
      vitro culture and in vivo serial transplantation. The expression profiles of ATP
      binding cassette (ABC) protein transporters and stem cell-related genes were
      examined by RT-PCR and western blot analysis. The human colon cancer cell lines
      SW480, Lovo and HCT116 contain 1.1 +/- 0.10, 0.93 +/- 0.11 and 1.33 +/- 0.05% SP
      cells, respectively. Flow cytometry analysis revealed that SP cells could
      differentiate into SP and NSP cells. SP cells had a higher proliferation potency
      and CFE than NSP cells. Compared to NSP cells, SP cells were also more resistant
      to CDDP and 5-FU, and were more invasive and displayed increased tumorigenic
      ability. Moreover, SP cells showed higher mRNA and protein expression of ABCG2,
      MDR1, OCT-4, NANOG, SOX-2, CD44 and CD133. SP cells isolated from human colon
      cancer cell lines harbor CSC properties that may be related to the invasive
      potential and therapeutic resistance of colon cancer.

PMID- 24926882
TI  - Artificial solid electrolyte interphase to address the electrochemical
      degradation of silicon electrodes.
AB  - Electrochemical degradation on silicon (Si) anodes prevents them from being
      successfully used in lithium (Li)-ion battery full cells. Unlike the case of
      graphite anodes, the natural solid electrolyte interphase (SEI) films generated
      from carbonate electrolytes do not self-passivate on Si, causing continuous
      electrolyte decomposition and loss of Li ions. In this work, we aim at solving
      the issue of electrochemical degradation by fabricating artificial SEI films
      using a solid electrolyte material, lithium phosphorus oxynitride (Lipon), which
      conducts Li ions and blocks electrons. For Si anodes coated with Lipon of 50 nm
      or thicker, a significant effect is observed in suppressing electrolyte
      decomposition, while Lipon of thinner than 40 nm has a limited effect. Ionic and
      electronic conductivity measurements reveal that the artificial SEI is effective
      when it is a pure ionic conductor, but electrolyte decomposition is only
      partially suppressed when the artificial SEI is a mixed electronic-ionic
      conductor. The critical thickness for this transition in conducting behavior is
      found to be 40-50 nm. This work provides guidance for designing artificial SEI
      films for high-capacity Li-ion battery electrodes using solid electrolyte
      materials. 

PMID- 24926881
TI  - Vitamin D deficiency causes defective resistance to Aspergillus fumigatus in mice
      via aggravated and sustained inflammation.
AB  - BACKGROUND: Vitamin D plays an important role in pulmonary resistance and
      immunity, and its deficiency has been linked to various respiratory infections.
      Little is known about the effect of vitamin D deficiency on host pulmonary
      defense to Aspergillus fumigatus (A. fumigatus). METHODS: Mice raised on vitamin
      D sufficient or deficient diets were infected intratracheally with A. fumigatus
      conidia. Mortality, fungal growth, weight loss and lung histology were monitored.
      Alveolar macrophages (AMs) were stimulated with A. fumigatus conidia in vitro.
      The kinetics of pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6),
      chemokines (CXCL1, CCL3), and pattern recognition receptors (Toll-like receptor
      [TLR] 2, TLR 4 and dectin-1) expression in the lungs and AMs were measured.
      RESULTS: Upon A. fumigatus infection, vitamin D deficient mice showed higher
      mortality, greater fungal load, and more weight loss than its sufficient
      counterparts. Vitamin D deficient mice demonstrated aggravated and prolonged
      histological evidence of lung inflammation as well as enhanced BAL cell counts,
      dominated by neutrophils after A. fumigatus inoculation. Increased basal levels
      of pro-inflammatory cytokines in the lungs and AMs from naive vitamin D deficient
      mice were observed. Upon A. fumigatus exposure, vitamin D deficiency led to
      enhanced and sustained expression of TNF-alpha, IL-1beta, IL-6, CXCL1 and CCL3
      both in vivo and in vitro. Up-regulation of TLR2, TLR4 and dectin-1was observed
      in the lungs and AMs from vitamin D deficient mice both at baseline and after A.
      fumigatus exposure. CONCLUSIONS: Vitamin D deficiency causes defective pulmonary
      resistance to A. fumigatus in mice, possibly by the enhanced basal expression of
      pattern recognition receptors and pro-inflammatory cytokines, which induced
      excessive inflammatory response in response to A. fumigatus challenge.

PMID- 24926883
TI  - Serum progesterone elevation adversely affects cumulative live birth rate in
      different ovarian responders during in vitro fertilization and embryo transfer: a
      large retrospective study.
AB  - In order to explore the relationship between serum progesterone (P) level on the
      day of human chorionic gonadotrophin (HCG) administration and cumulative live
      birth rate in patients with different ovarian response during in vitro
      fertilization (IVF), we carried out this retrospective cohort study including a
      total of 4,651 patients undergoing their first IVF cycles from January 2011 to
      December 2012. All patients with a final live birth outcome (4,332 patients) were
      divided into three groups according to ovarian response: poor ovarian responder
      (<=5 oocytes, 785 patients), intermediate ovarian responder (6-19 oocytes, 3065
      patients) and high ovarian responder (>=20 oocytes, 482 patients). The thresholds
      for serum P elevation were 1.60 ng/ml, 2.24 ng/ml, and 2.50 ng/ml for poor,
      intermediate, and high ovarian responders, respectively. Cumulative live birth
      rate per oocyte retrieval cycle was calculated in each group. The relationship
      between serum P level and cumulative live birth rate was evaluated by both
      univariate and multivariate logistic regression analysis. Cumulative live birth
      rate per oocyte retrieval cycle was inversely associated with serum P level in
      patients with different ovarian response. For all responders, patients with
      elevated P level had significantly higher number of oocytes retrieved, but lower
      high quality embryo rate, and lower cumulative live birth rate compared with
      patients with normal serum P level. In addition, serum P level adversely affected
      cumulative live birth rate by both univariate and multivariate logistic
      regression analysis, independent of ovarian response. Serum P elevation on the
      day of HCG administration adversely affects cumulative live birth rate per oocyte
      retrieval cycle in patients with different ovarian response. 

PMID- 24926884
TI  - Nanowire waveguides launching single photons in a Gaussian mode for ideal fiber
      coupling.
AB  - Quantum communication as well as integrated photonic circuits require single
      photons propagating in a well-defined Gaussian mode. However, tailoring the
      emission mode to a Gaussian remains an unsolved challenge for solid-state quantum
      emitters due to their random positioning in the host material or photonic
      structure. Here, we overcome these limitations by embedding a semiconductor
      quantum dot in a tapered nanowire waveguide. Owing to the deterministic
      positioning of the emitter in the waveguide, we demonstrate a Gaussian emission
      profile in the far field. Hence, we further couple the emission into a single
      mode optical fiber with a record efficiency of 93%, thereby addressing a major
      hurdle for practical implementation of single photon sources in emerging photonic
      technologies. 

PMID- 24926885
TI  - Resistance of oral squamous cell carcinoma cells to cetuximab is associated with
      EGFR insensitivity and enhanced stem cell-like potency.
AB  - Cetuximab, a specific anti-epidermal growth factor receptor (EGFR) monoclonal
      antibody, is used in cancer treatment. Although development of resistance to
      cetuximab is well recognized, the underlying mechanisms remain unclear. In the
      present study, we characterized cetuximab-resistant oral squamous cell carcinoma
      (OSCC) cell lines. The human OSCC cell lines HSC3, HSC4 and SAS were used in the
      present study. Effects of inhibitors including cetuximab on growth in cells were
      assessed by MTT assays. Southern blotting and immunofluorescence analysis were
      performed to examine protein expression and localization. Sphere formation was
      used to characterize stem cell-like properties. Floating aggregation culture was
      used for anchorage-independent growth. Cetuximab inhibited proliferation of HSC3
      and HSC4 cells, but not SAS cells. Proliferation of all three cell lines was
      inhibited by the EGFR/ErbB2/ErbB4 inhibitor II. The EGFR inhibitor AG1478
      strongly inhibited HSC3 and HSC4 proliferation, but that of SAS cells only
      moderately. EGFR proteins were localized on cell surface and phosphorylated in
      all three cell lines. SAS cells could proliferate in serum-free monolayer culture
      and formed spheres from single cells in floating culture. HSC3 and HSC4 could not
      proliferate under serum-free culture conditions and could not form spheres.
      Growth of SAS spheres required serum, and was inhibited by both AG1478 and
      cetuximab. Thus, cetuximab-resistant SAS cells not only engaged in EGFR
      independent growth but also exhibited stem cell-like properties. However, growth
      was EGFR-dependent in aggregation culture, and the SAS cell aggregates became
      cetuximab-sensitive. This suggests that cetuximab sensitivity is not only cell
      type-dependent but is also affected by the growth microenvironment.

PMID- 24926887
TI  - Stereoselective alpha-fluorination of N-acyloxazolidinones at room temperature
      within 1 h.
AB  - A direct alpha-fluorination of N-acyloxazolidinones based on the unique
      reactivity of group IVa metal enolates has been developed. The reaction is an
      experimentally simple, low-cost, quick, and energy-efficient alternative for
      asymmetric alpha-fluorination of N-acyloxazolidinones. Preliminary studies have
      shown compatibility with alkyl, alkenyl, and alkynyl, aromatic, and several
      heteroaromatic substituents. High diastereoselectivities have been achieved with
      most substrates tested, and the reaction is typically complete within 1 h at
      ambient temperature. 

PMID- 24926886
TI  - Offroad re-entry catheter system for subintimal recanalization of chronic total
      occlusions in femoropopliteal arteries: primary safety and effectiveness results
      of the re-route trial.
AB  - AIM: Aim of the study was to provide additional clinical data regarding the
      safety and technical success of the OffRoad Re-Entry Catheter System (Boston
      Scientific, Natick, MA, USA) for subintimal recanalization of chronic total
      occlusions (CTO) in the femoropopliteal arteries. METHODS: A total of 92 patients
      (mean age 70.3+/-10.6 years; 70% male) were enrolled in this prospective, single
      arm, post-market study conducted at 12 European centers. Patients were required
      to have claudication or critical limb ischemia and a CTO lesion in a native
      femoropopliteal artery. The primary safety endpoint was the composite rate of
      device-related major adverse events (MAEs; i.e., death, perforation requiring
      intervention, clinically significant peripheral embolism, and major amputation of
      the treated lower limb) at 30 days. Effectiveness was based on device technical
      success, defined as placement of a guidewire in the true lumen distal to a CTO.
      RESULTS: Ninety patients were evaluable for the primary safety endpoint. The 30
      day device-related MAE rate was 3.3% (3/90), with an upper confidence bound of
      6.5%, which was lower than the prespecified performance goal of 15%. All 3 events
      were clinically significant peripheral emboli. Technical success was 84.8%
      (78/92) with a lower confidence bound of 78.6%, which exceeded the prespecified
      performance goal of 76%. A decrease of >=1 Rutherford category was observed in
      75% (65/87) of patients at the 30 day visit. CONCLUSION: The Re-ROUTE trial
      results demonstrate acceptable performance of the OffRoad system in terms of
      safety and technical success for the recanalization of femoropopliteal CTOs.

PMID- 24926888
TI  - Structure and dynamics of the HIV-1 frameshift element RNA.
AB  - The HIV-1 ribosomal frameshift element is highly structured, regulates
      translation of all virally encoded enzymes, and is a promising therapeutic
      target. The prior model for this motif contains two helices separated by a three
      nucleotide bulge. Modifications to this model were suggested by SHAPE chemical
      probing of an entire HIV-1 RNA genome. Novel features of the SHAPE-directed model
      include alternate helical conformations and a larger, more complex structure.
      These structural elements also support the presence of a secondary frameshift
      site within the frameshift domain. Here, we use oligonucleotide-directed
      structure perturbation, probing in the presence of formamide, and in-virion
      experiments to examine these models. Our data support a model in which the
      frameshift domain is anchored by a stable helix outside the conventional domain.
      Less stable helices within the domain can switch from the SHAPE-predicted to the
      two-helix conformation. Translational frameshifting assays with frameshift domain
      mutants support a functional role for the interactions predicted by and specific
      to the SHAPE-directed model. These results reveal that the HIV-1 frameshift
      domain is a complex, dynamic structure and underscore the importance of analyzing
      folding in the context of full-length RNAs. 

PMID- 24926889
TI  - Silver-catalyzed highly regioselective formal hydroboration of alkynes.
AB  - A silver(I)-N-heterocyclic carbene complex has proven to be a potent catalyst for
      formal hydroboration of alkynes, providing a variety of borylalkenes in regio-
      and stereoselective manners. Under the silver catalysis, allenes also undergo
      regioselective hydroboration to give borylalkenes. 

PMID- 24926890
TI  - Biophysical, mutational, and functional investigation of the chromophore-binding
      pocket of light-oxygen-voltage photoreceptors.
AB  - As light-regulated actuators, sensory photoreceptors underpin optogenetics and
      numerous applications in synthetic biology. Protein engineering has been applied
      to fine-tune the properties of photoreceptors and to generate novel actuators.
      For the blue-light-sensitive light-oxygen-voltage (LOV) photoreceptors, mutations
      near the flavin chromophore modulate response kinetics and the effective light
      responsiveness. To probe for potential, inadvertent effects on receptor activity,
      we introduced these mutations into the engineered LOV photoreceptor YF1 and
      determined their impact on light regulation. While several mutations severely
      impaired the dynamic range of the receptor (e.g., I39V, R63K, and N94A), residue
      substitutions in a second group were benign with little effect on regulation
      (e.g., V28T, N37C, and L82I). Electron paramagnetic resonance and absorption
      spectroscopy identified correlated effects for certain of the latter mutations on
      chromophore environment and response kinetics in YF1 and the LOV2 domain from
      Avena sativa phototropin 1. Carefully chosen mutations provide a powerful means
      to adjust the light-response function of photoreceptors as demanded for diverse
      applications. 

PMID- 24926891
TI  - Polyketides from the cultured lichen mycobiont of a Vietnamese Pyrenula sp.
AB  - A spore-derived mycobiont of a crustose Pyrenula sp. lichen collected in Vietnam
      was cultivated on a malt-yeast extract medium supplemented with 10% sucrose.
      Chemical investigation of the cultivated colonies led to the isolation of eight
      new alkylated decalin-type polyketides (1-8) along with three known compounds.
      The structures of these compounds were elucidated by spectroscopic and chemical
      means. This is the first instance of this type of polyketide being isolated from
      a cultured lichen mycobiont. The isolated polyketides 1 and 7 exhibited
      inhibitory activities against mammalian DNA polymerases alpha and beta with IC50
      values ranging from 8.1 to 19.5 MUM. Compound 1 showed cytotoxic effects against
      the HCT116 human colon carcinoma cultured cell line with an IC50 value of 6.4 +/-
      0.7 MUM. 

PMID- 24926892
TI  - Transcatheter pulmonary valve replacement by hybrid approach using a novel
      polymeric prosthetic heart valve: proof of concept in sheep.
AB  - BACKGROUND: Since 2000, transcatheter pulmonary valve replacement has steadily
      advanced. However, the available prosthetic valves are restricted to
      bioprosthesis which have defects like poor durability. Polymeric heart valve is
      thought as a promising alternative to bioprosthesis. In this study, we introduced
      a novel polymeric transcatheter pulmonary valve and evaluated its feasibility and
      safety in sheep by a hybrid approach. METHODS: We designed a novel polymeric
      trileaflet transcatheter pulmonary valve with a balloon-expandable stent, and the
      valve leaflets were made of 0.1-mm expanded polytetrafluoroethylene (ePTFE)
      coated with phosphorylcholine. We chose glutaraldehyde-treated bovine pericardium
      valves as control. Pulmonary valve stents were implanted in situ by a hybrid
      transapical approach in 10 healthy sheep (8 for polymeric valve and 2 for bovine
      pericardium valve), weighing an average of 22.5+/-2.0 kg. Angiography and cardiac
      catheter examination were performed after implantation to assess immediate
      valvular functionality. After 4-week follow-up, angiography, echocardiography,
      computed tomography, and cardiac catheter examination were used to assess early
      valvular function. One randomly selected sheep with polymeric valve was
      euthanized and the explanted valved stent was analyzed macroscopically and
      microscopically. FINDINGS: Implantation was successful in 9 sheep. Angiography at
      implantation showed all 9 prosthetic valves demonstrated orthotopic position and
      normal functionality. All 9 sheep survived at 4-week follow-up. Four-week follow
      up revealed no evidence of valve stent dislocation or deformation and normal
      valvular and cardiac functionality. The cardiac catheter examination showed the
      peak-peak transvalvular pressure gradient of the polymeric valves was 11.9+/-5.0
      mmHg, while that of two bovine pericardium valves were 11 and 17 mmHg. Gross
      morphology demonstrated good opening and closure characteristics. No thrombus or
      calcification was seen macroscopically. CONCLUSIONS: This design of the novel
      ePTFE transcatheter pulmonary valve is safe and effective to deploy in sheep by
      hybrid approach, and the early valvular functionality is good.

PMID- 24926894
TI  - Efficient optical trapping of CdTe quantum dots by femtosecond laser pulses.
AB  - The development in optical trapping and manipulation has been showing rapid
      progress, most of it is in the small particle sizes in nanometer scales,
      substituting the conventional continuous-wave lasers with high-repetition-rate
      ultrashort laser pulse train and nonlinear optical effects. Here, we evaluate two
      photon absorption in optical trapping of 2.7 nm-sized CdTe quantum dots (QDs)
      with high-repetition-rate femtosecond pulse train by probing laser intensity
      dependence of both Rayleigh scattering image and the two-photon-induced
      luminescence spectrum of the optically trapped QDs. The Rayleigh scattering
      imaging indicates that the two-photon absorption (TPA) process enhances trapping
      ability of the QDs. Similarly, a nonlinear increase of the two-photon-induced
      luminescence with the incident laser intensity fairly indicates the existence of
      the TPA process. 

PMID- 24926893
TI  - Reference genes for quantitative gene expression studies in multiple avian
      species.
AB  - Quantitative real-time PCR (qPCR) rapidly and reliably quantifies gene expression
      levels across different experimental conditions. Selection of suitable reference
      genes is essential for meaningful normalization and thus correct interpretation
      of data. In recent years, an increasing number of avian species other than the
      chicken has been investigated molecularly, highlighting the need for an
      experimentally validated pan-avian primer set for reference genes. Here we report
      testing a set for 14 candidate reference genes (18S, ABL, GAPDH, GUSB, HMBS,
      HPRT, PGK1, RPL13, RPL19, RPS7, SDHA, TFRC, VIM, YWHAZ) on different tissues of
      the mallard (Anas platyrhynchos), domestic chicken (Gallus gallus domesticus),
      common crane (Grus grus), white-tailed eagle (Haliaeetus albicilla), domestic
      turkey (Meleagris gallopavo f. domestica), cockatiel (Nymphicus hollandicus),
      Humboldt penguin (Sphenicus humboldti), ostrich (Struthio camelus) and zebra
      finch (Taeniopygia guttata), spanning a broad range of the phylogenetic tree of
      birds. Primer pairs for six to 11 genes were successfully established for each of
      the nine species. As a proof of principle, we analyzed expression levels of 10
      candidate reference genes as well as FOXP2 and the immediate early genes, EGR1
      and CFOS, known to be rapidly induced by singing in the avian basal ganglia. We
      extracted RNA from microbiopsies of the striatal song nucleus Area X of adult
      male zebra finches after they had sang or remained silent. Using three different
      statistical algorithms, we identified five genes (18S, PGK1, RPS7, TFRC, YWHAZ)
      that were stably expressed within each group and also between the singing and
      silent conditions, establishing them as suitable reference genes. In conclusion,
      the newly developed pan-avian primer set allows accurate normalization and
      quantification of gene expression levels in multiple avian species. 

PMID- 24926896
TI  - Mindfulness, self-compassion, and empathy among health care professionals: a
      review of the literature.
AB  - The relationship between mindfulness and self-compassion is explored in the
      health care literature, with a corollary emphasis on reducing stress in health
      care workers and providing compassionate patient care. Health care professionals
      are particularly vulnerable to stress overload and compassion fatigue due to an
      emotionally exhausting environment. Compassion fatigue among caregivers in turn
      has been associated with less effective delivery of care. Having compassion for
      others entails self-compassion. In Kristin Neff's research, self-compassion
      includes self-kindness, a sense of common humanity, and mindfulness. Both
      mindfulness and self-compassion involve promoting an attitude of curiosity and
      nonjudgment towards one's experiences. Research suggests that mindfulness
      interventions, particularly those with an added lovingkindness component, have
      the potential to increase self-compassion among health care workers. Enhancing
      focus on developing self-compassion using MBSR and other mindfulness
      interventions for health care workers holds promise for reducing perceived stress
      and increasing effectiveness of clinical care. 

PMID- 24926895
TI  - A general pairwise interaction model provides an accurate description of in vivo
      transcription factor binding sites.
AB  - The identification of transcription factor binding sites (TFBSs) on genomic DNA
      is of crucial importance for understanding and predicting regulatory elements in
      gene networks. TFBS motifs are commonly described by Position Weight Matrices
      (PWMs), in which each DNA base pair contributes independently to the
      transcription factor (TF) binding. However, this description ignores correlations
      between nucleotides at different positions, and is generally inaccurate:
      analysing fly and mouse in vivo ChIPseq data, we show that in most cases the PWM
      model fails to reproduce the observed statistics of TFBSs. To overcome this
      issue, we introduce the pairwise interaction model (PIM), a generalization of the
      PWM model. The model is based on the principle of maximum entropy and explicitly
      describes pairwise correlations between nucleotides at different positions, while
      being otherwise as unconstrained as possible. It is mathematically equivalent to
      considering a TF-DNA binding energy that depends additively on each nucleotide
      identity at all positions in the TFBS, like the PWM model, but also additively on
      pairs of nucleotides. We find that the PIM significantly improves over the PWM
      model, and even provides an optimal description of TFBS statistics within
      statistical noise. The PIM generalizes previous approaches to interdependent
      positions: it accounts for co-variation of two or more base pairs, and predicts
      secondary motifs, while outperforming multiple-motif models consisting of
      mixtures of PWMs. We analyse the structure of pairwise interactions between
      nucleotides, and find that they are sparse and dominantly located between
      consecutive base pairs in the flanking region of TFBS. Nonetheless, interactions
      between pairs of non-consecutive nucleotides are found to play a significant role
      in the obtained accurate description of TFBS statistics. The PIM is
      computationally tractable, and provides a general framework that should be useful
      for describing and predicting TFBSs beyond PWMs. 

PMID- 24926897
TI  - Overview of qualitative research.
AB  - Qualitative research methods are a robust tool for chaplaincy research questions.
      Similar to much of chaplaincy clinical care, qualitative research generally works
      with written texts, often transcriptions of individual interviews or focus group
      conversations and seeks to understand the meaning of experience in a study
      sample. This article describes three common methodologies: ethnography, grounded
      theory, and phenomenology. Issues to consider relating to the study sample,
      design, and analysis are discussed. Enhancing the validity of the data, as well
      reliability and ethical issues in qualitative research are described. Qualitative
      research is an accessible way for chaplains to contribute new knowledge about the
      sacred dimension of people's lived experience. 

PMID- 24926899
TI  - Theoretical studies on anatase and less common TiO2 phases: bulk, surfaces, and
      nanomaterials.

PMID- 24926900
TI  - Identification of photosynthesis inhibitors of pelagic marine algae using 96-well
      plate microfractionation for enhanced throughput in effect-directed analysis.
AB  - Because of large-scale production and use of an increasing diversity of chemicals
      in modern society, estuarine and coastal waters may be contaminated with numerous
      substances. Some of these compounds have the potential to affect microalgae at
      the base of the pelagic food chain. Therefore, we identified the main chemical
      stressors that negatively affect the effective photosystem II efficiency
      (phiPSII) in marine microalgae of the Dutch estuarine and coastal waters. An
      enhanced effect-directed analysis (EDA) was carried out by combining reversed
      phase ultra performance liquid chromatography fractionation of extracts from
      passive samplers, followed by effect assessment using the pulse amplitude
      modulation fluorometry assay and chemical analysis of biologically active
      fractions using high-resolution mass spectrometry. This study focuses on a novel
      microfractionation technique using 96-well plates to enhance throughput in EDA,
      structure elucidation, and the analytical and effect confirmation of the
      compounds that are identified. Although there are numerous unknown compounds
      present in estuarine and coastal waters, our EDA study shows that atrazine,
      diuron, irgarol, isoproturon, terbutryn, and terbutylazine are the main
      contributors to the observed effect on the phiPSII of marine microalgae. 

PMID- 24926901
TI  - Response rate and factors affecting the outcome of a fixed dose of RAI-131
      therapy in Graves' disease: a 10-year Egyptian experience.
AB  - The aim of this study was to evaluate response and compare the success rate of
      two different doses of iodine-131 ((131)I) therapy in the treatment of Graves'
      disease and investigate the factors that may affect outcome. A retrospective
      analysis was carried out on 321 patients treated with (131)I for Graves' disease.
      Group 1 (155 patients) received 8 mCi and group 2 (166 patients) received 12 mCi.
      The therapy was considered successful if euthyroidism or hypothyroidism was
      achieved within 1 year of therapy. The outcome was compared with multiple
      parameters. A significant difference in the outcome between the two groups was
      found in favor of the second group (P<0.001). Logistic regression analysis showed
      that lower dose, technetium-99m pertechnetate thyroid uptake greater than 20.9%,
      and moderate and marked goiter were independent variables associated
      significantly with a lower response rate (odds ratio 2.601, 4.023, and 3.309,
      respectively), whereas previous surgical treatment was associated with a higher
      response rate (odds ratio 3.071). No correlation was found between outcome and
      age, presence of exophthalmos, previous treatment with methimazole, and its
      duration. The response rate to the second dose was significantly increased
      compared with the first one by 27.8%; there was no correlation among the above
      mentioned factors and its outcome. The third dose controlled the disease in 81.3%
      of the remaining patients and control was achieved in the rest after the fourth
      dose. (131)I is a very effective therapy for Graves' disease, with a cure rate of
      100% after four doses. Higher first dose activity is recommended in the presence
      of poor prognostic factors. The second dose is not necessarily increased in the
      nonresponders.

PMID- 24926902
TI  - Optimization and application of TiO2/Ti-Pt photo fuel cell (PFC) to effectively
      generate electricity and degrade organic pollutants simultaneously.
AB  - A TiO2/Ti-Pt photo fuel cell (PFC) was established to generate electricity and
      degrade organic pollutants simultaneously. The electricity generation was
      optimized through investigation the influences of photoanode calcination
      temperature and dissolve oxygen on the resistances existing in PFC. TiO2 light
      quantum yield was also improved in PFC which resulted in a higher PC degradation
      efficiency. Two kinds of real textile wastewaters were also employed in this PFC
      system, 62.4% and 50.0% Coulombic efficiency were obtained for 8 h treatment.
      These refractory wastewaters with high salinity may become good fuels in PFC
      because a) TiO2 has no selectivity and can degrade nearly any organic substance,
      b) no more electrolyte is needed due to the high salinity, c) the energy in
      wastes can be recovered to generate electricity. The electricity generated by the
      PFC was further applied on a TiO2/Ti rotating disk photoelectrocatalytic reactor.
      A bias voltage between 0.6 and 0.75 V could be applied and the PC degradation
      efficiency was significantly improved. This result was similar with that obtained
      by a 0.7 V DC power.

PMID- 24926904
TI  - A case of feline gastrointestinal eosinophilic sclerosing fibroplasia mimicking
      metastatic neoplasia.
AB  - CASE HISTORY: A 7-year-old cat developed sporadic vomiting, reduced appetite, and
      weight loss over the previous 3 months. CLINICAL FINDINGS: Palpation revealed a
      large mid-abdominal mass and the cat had marked eosinophilia. The cat
      progressively lost weight over the next 7 weeks when euthanasia was performed.
      PATHOLOGICAL FINDINGS: Necropsy revealed a 3 cm diameter firm white intramural
      mass in the colon and another in the pylorus. Mesenteric and cranial mediastinal
      lymph nodes were firm, pale, and enlarged. Histopathological examination revealed
      foci of necrosis surrounded by thick dense collagen trabeculae and predominantly
      eosinophilic inflammation within the intestine and lymph nodes. Marked
      eosinophilic infiltration of the liver was also present. DIAGNOSIS: The lesions
      were consistent with gastrointestinal eosinophilic sclerosing fibroplasia
      (FGESF). CLINICAL RELEVANCE: This is the first report of FGESF in a New Zealand
      cat and the first time lesions of FGESF have been observed in extra-abdominal
      tissues. Intestinal neoplasia can be clinically identical to FGESF and
      histopathology is required for differentiation. Evidence suggests that FGESF has
      a more favourable prognosis than intestinal neoplasia.

PMID- 24926903
TI  - The challenge of producing ubiquitinated proteins for structural studies.
AB  - Protein ubiquitination is an important post-translational modification involved
      in several essential signalling pathways. It has different effects on the target
      protein substrate, i.e., it can trigger the degradation of the protein in the
      proteasome, change the interactions of the modified protein with its partners, or
      affect its localization and activity. In order to understand the molecular
      mechanisms underlying the consequences of protein ubiquitination, scientists have
      to face the challenging task of producing ubiquitinated proteins for structural
      characterization with X-ray crystallography and/or nuclear magnetic resonance
      (NMR) spectroscopy. These techniques require milligrams of homogeneous samples of
      high purity. The strategies proposed so far for the production of ubiquitinated
      proteins can be divided into two groups, i.e., chemical (or non-enzymatic) and
      enzymatic methodologies. In this review, we summarize the still very sparse
      examples available in the literature that describe successful production of
      ubiquitinated proteins amenable for biochemical and structural studies, and
      discuss advantages and disadvantages of the techniques proposed. We also give a
      perspective of the direction in which the field might evolve. 

PMID- 24926905
TI  - The insight interview: a new tool for measuring deficits in awareness after
      traumatic brain injury.
AB  - OBJECTIVE: Awareness deficits are common after traumatic brain injury (TBI);
      however, relatively little is known of awareness deficits in the early stages
      post-injury. This study outlines the development of a new tool, 'The Insight
      Interview', designed to measure awareness across different domains (awareness of
      change, severity of deficits, current and future functional consequences) from 3
      months post-TBI. METHODS: Forty-three patients with at least a severe TBI, their
      nominated family member and treating clinician were all administered different
      versions of the Insight Interview during the patient's inpatient stay. Awareness
      was measured; (1) by calculating a discrepancy score between the patient's and
      their family informant's and/or clinician's ratings of the patient's abilities
      and (2) using interviewer-based ratings of the patients' responses to interview
      questions. RESULTS: Awareness differed depending upon the domain being assessed,
      with patients demonstrating greatest awareness in the current functional
      consequences domain. Evidence for a distinction between awareness of current and
      future functional consequences of impairments was also seen. Discrepancy scores
      and interviewer-based ratings showed good concordance. Adequate reliability and
      validity was demonstrated. CONCLUSION: The Insight Interview is a useful and
      valid tool for measuring awareness in the acute stages following TBI and
      highlights that awareness depends on domain assessed.

PMID- 24926906
TI  - Fantasy sports, real money: exploration of the relationship between fantasy
      sports participation and gambling-related problems.
AB  - Participation in fantasy sports increases annually. Wagering on fantasy sports is
      a form of gambling and researchers have found that fantasy sports participants
      are more likely to engage in other forms of sports betting than non-fantasy
      players; however, no published studies have examined whether there is a
      relationship between fantasy sports participation and gambling-related problems.
      Our study examined whether fantasy sports participation is associated with
      gambling-related problems among college students. We assessed fantasy sports
      participation and endorsement of DSM-5 gambling disorder (GD) criteria among a
      large convenience sample (N=1556) of college students via an online health
      survey. We found that 11.5% of respondents participated in fantasy sports in the
      past year, the majority of which were males. Logistic regression analyses
      indicated that males who play fantasy sports for money and females who play
      fantasy sports (for money or not) were more likely to experience gambling-related
      problems. 

PMID- 24926907
TI  - Risk perception and intention to quit among a tri-ethnic sample of nondaily,
      light daily, and moderate/heavy daily smokers.
AB  - INTRODUCTION: Although the relationship between risk perceptions and quit
      intentions has been established, few studies explore the potential impact of
      smoking level on these associations, and none have done so among diversely-aged
      samples of multiple ethnicities. METHODS: Participants, ranging in age from 25 to
      81, were 1133 nondaily smokers (smoked >=1 cigarette on 4 to 24days in the past
      30days), 556 light daily smokers (<=10 cigarettes per day), and 585 moderate to
      heavy daily smokers (>10 cigarettes per day). Each smoking level comprised
      approximately equal numbers of African Americans, Latinos, and Whites. A logistic
      regression analysis, adjusted for sociodemographics, self-rated health, time to
      the first cigarette of the day and smoking level, was used to examine the
      association between risk perception (perceived risk of acquiring lung cancer,
      lung disease, and heart disease) and intention to quit (<=6months versus
      >6months/never). A second adjusted model tested moderation by smoking level with
      an interaction term. RESULTS: Greater risk perception was associated with a
      higher odds of planning to quit within 6months (AOR=1.34, CI.95=1.24, 1.45).
      Smoking level did not moderate this association (p=.85). CONCLUSIONS: Results
      suggest that educating all smokers, irrespective of their smoking level, about
      increased risk of developing smoking-related diseases might be a helpful strategy
      to enhance their intention to make a smoking quit attempt.

PMID- 24926908
TI  - Pathways of family influence: alcohol use and disordered eating in daughters.
AB  - Models of addiction etiology and treatment emphasize the influence of family-of
      origin experiences. Using two addiction-related coping behaviors (ARCBs) common
      among college women (i.e., problematic alcohol use, disordered eating), we
      examined whether ARCBs in parents related to matching ARCBs in college women
      offspring. We expected that matching parental ARCBs would relate more strongly to
      the ARCBs in offspring than more distal/general family factors. A total of 197
      college women completed measures of family dynamics, parental difficulties with
      alcohol, family focus on appearance and weight, personal difficulties with
      alcohol use, and disordered eating. A significant indirect effect for family
      dysfunction on disordered eating and alcohol-related problems was found. That is,
      family relationship difficulties predicted parents' ARCBs, which predicted
      matching ARCBs in participants (e.g., parental alcohol problems predicted
      participant alcohol problems). Matched parental ARCBs were better predictors of
      participants' ARCBs than more general/distal family factors and non-matched
      ARCBs. Specifically, path analysis and testing of beta weights supported
      specificity of parental ARCBs for predicting matching offspring ARCBs.
      Implications of study findings for tailoring prevention efforts are discussed. 

PMID- 24926910
TI  - Range of motion, postural alignment, and LESS score differences of those with and
      without excessive medial knee displacement.
AB  - OBJECTIVE: To determine range of motion (ROM), postural alignment, and dynamic
      motion differences between those with and without medial knee displacement (MKD)
      during the overhead squat (OHS). We hypothesized those with MKD would have
      restricted ROM, differing postural alignment, and poorer quality dynamic motion
      than those without MKD. DESIGN: Observational. SETTING: University Research
      Laboratory. PARTICIPANTS: Ninety-seven healthy recreationally active college-aged
      individuals. INDEPENDENT VARIABLES: Groups were determined by the presence (MKD
      group) or absence (control group) of MKD during an OHS. MAIN OUTCOME MEASURES:
      Range of motion measures were active and passive ankle dorsiflexion with the knee
      straight and bent, hip internal and external rotation, and hip abduction.
      Postural alignment measures were Q angle, navicular drop, and genu recurvatum.
      Quality of dynamic motion was measured using total Landing Error Scoring System
      (LESS) score. RESULTS: The MKD group had significantly less active (P = 0.017)
      and passive (P = 0.045) ankle dorsiflexion with the knee straight, as well as
      significantly increased Q angle (P = 0.004) and decreased navicular drop (P =
      0.009). There were no significant differences in total LESS score or the other
      outcome measures. CONCLUSIONS: There is select ROM, such as ankle dorsiflexion,
      and postural measures clinicians can screen for that may be related to increased
      MKD and theoretically elevated risk of injury.

PMID- 24926909
TI  - Posttraumatic stress disorder, smoking, and cortisol in a community sample of
      pregnant women.
AB  - BACKGROUND: The prevalence of posttraumatic stress disorder (PTSD) in the United
      States is higher among pregnant women than women generally. PTSD is related to
      adverse birth outcomes via physiological and behavioral alterations, such as
      smoking. METHODS: We utilize salivary cortisol measures to examine how traumatic
      stress, smoking and the hypothalamic-pituitary-adrenal axis interact. Pregnant
      women (n=395) gave cortisol specimens as part of a cohort study of PTSD and
      pregnancy at three health systems in the Midwestern United States. Women were
      divided into three groups: nonsmokers, quitters (who stopped smoking during
      pregnancy), and pregnancy smokers. Mean cortisol values at three points,
      sociodemographics, trauma history, and PTSD were compared across groups. We
      assessed the association of smoking group and PTSD with late afternoon cortisol
      levels. RESULTS: Smokers, quitters, and nonsmokers differed on demographic risk
      factors and PTSD symptom load. Late afternoon and bedtime cortisol measures were
      significantly positively correlated with smoking in pregnancy, with smokers with
      PTSD presenting the highest cortisol levels. Regression analysis showed that
      smoking in pregnancy was associated with higher late afternoon cortisol in an
      additive manner with PTSD symptoms. CONCLUSIONS: Smoking appears to have a
      different relationship with cortisol level for those with and without PTSD. This
      is the first study to show additive effects of smoking and PTSD on cortisol
      levels in pregnant women. Since high cortisol, smoking, and PTSD have been shown
      to adversely affect perinatal outcomes, and since those continuing to smoke in
      pregnancy had the highest PTSD symptom load, PTSD-specific smoking cessation
      programs in maternity settings are warranted.

PMID- 24926911
TI  - A closer look at overuse injuries in the pediatric athlete.
AB  - OBJECTIVE: To examine male-female differences in pediatric overuse sports
      injuries. STUDY DESIGN: Cross-sectional epidemiological study. SETTING: Tertiary
      level sports medicine division in a large academic pediatric medical center.
      PARTICIPANTS: Five percent probability sample of patients 5 to 17 years seen from
      January 1, 2000 to December 31, 2009. About 3813 charts reviewed. Final study
      cohort included 1614 patients. INTERVENTION: Nonlinear decomposition analysis of
      male-female differences in overuse injuries. MAIN OUTCOME MEASURES: Age, body
      mass index, history of previous injury, and activity type (contact/collision,
      team vs individual, "high overuse"). RESULTS: Females sustained approximately
      half of the total injuries. Fifty-two percent of the injuries were overuse, 61%
      to the lower extremity. A high proportion of tennis players, swimmers, dancers,
      track athletes, runners, gymnasts, and cheerleaders were seen for overuse
      injuries. Females sustained more overuse injuries versus males (63% and 40%,
      respectively). Males playing team sports have a 5.3 times higher likelihood of
      being seen for an overuse injury compared with males not playing team sports (P <
      0.01). High-overuse sport participation increased overuse injury odds by a factor
      of 10 for males versus 3.6 for females (P <= 0.01 for males and females). Forty
      six percent of the male-female difference in overuse injuries could be attributed
      to sport/activity characteristics-contact/collision, team, and high overuse.
      CONCLUSIONS: A large proportion of the sex discrepancy in overuse injuries in
      this cohort was attributed to compositional differences in sports played. Future
      research is needed to investigate the independent effect of sex on risk for
      pediatric sports injuries. CLINICAL RELEVANCE: This study provides a unique
      analysis of male-female differences in pediatric sports injuries and is the first
      study to estimate the impact of the different characteristics (ie, collision,
      team, high overuse) of sports children play on overuse injuries sustained by
      young athletes. The findings will help guide future prevention efforts.

PMID- 24926912
TI  - Stress fracture of the supracondylar process of the humerus in a professional
      tennis player.
AB  - The supracondylar process of the humerus is an anatomic variant present in 1% of
      the population associated with a fibrous band, the ligament of Struthers that
      attaches it to the medial epicondyle, and may serve as a proximal origin of a
      fascicle of the pronator teres. Fractures of the supracondylar process of the
      humerus are extremely rare. To the best of our knowledge, this is the first
      report of a stress fracture of the supracondylar process. We present the case of
      a professional tennis player with a stress fracture of the supracondylar process
      who underwent surgery to avoid possible displacement and neurovascular
      complications. Clinicians should consider the diagnosis of a supracondylar
      process fracture with or without neurovascular compression when examining
      athletes with otherwise unexplained arm or elbow pain. Stress fracture of the
      supracondylar process may be secondary to the excessive traction of the pronator
      teres.

PMID- 24926913
TI  - Exercise addiction in men is associated with lower fat-adjusted leptin levels.
AB  - OBJECTIVE: To test a hypothesized association between resting leptin levels
      (adjusted for body fat percentage) and symptoms of primary exercise addiction.
      DESIGN: Cross-sectional design. SETTING: Habitual amateur exercisers
      participating in running, fitness, weight training, and biking. PARTICIPANTS:
      Twenty men with exercise addiction as defined by the Exercise Addiction Inventory
      (EAI scores 24-30) and 20 men in an exercise control group (EAI scores 6-16)
      matched on body mass index. MAIN OUTCOME MEASURES: Plasma leptin and sex hormones
      were measured in blood samples collected under fasting and resting conditions.
      Body composition was assessed by dual-energy x-ray absorptiometry. Eating
      disorder symptoms were identified by the Eating Disorder Inventory 2. RESULTS:
      The exercise addiction group had significantly (P < 0.001) lower leptin levels
      (1.1 MUg/L, SD = 1.3) than controls (4.3 MUg/L, SD = 2.9). Even when adjusted for
      body fat percentage, the addiction group had significantly (P < 0.001) lower
      leptin levels (0.1 MUg/L, SD = 0.1) than the controls (0.2 MUg/L, SD = 0.1). Body
      fat-adjusted leptin correlated with free bioavailable testosterone, but it was
      only significant in nonaddictive exercisers. None of the exercisers seemed to
      suffer from an eating disorder. CONCLUSIONS: This is the first study showing that
      excessive training in exercise addiction is associated with low levels of body
      fat-adjusted leptin levels. CLINICAL RELEVANCE: Hypoleptinemia could be involved
      in the pathogenesis of exercise addiction. However, further studies are needed to
      explore the potential causal relationship.

PMID- 24926914
TI  - Simultaneous solvent and J-modulation suppression in PGSTE-based diffusion
      experiments.
AB  - The most favourable solvent suppression methods that have been applied to PGSTE
      experiments for the measurement of diffusion are WATERGATE and excitation
      sculpting. However, both methods come with significant J-modulation line-shape
      distortions on multiplets, a phenomenon that is known to be of particular concern
      for DOSY data processing. Here, two new PGSTE experiments are proposed that
      suppress both the solvent peak and J-modulation based on the perfect echo
      WATERGATE sequence. This allows narrow suppression bandwidths and thus
      measurement of diffusion on peaks close to the solvent peak. Both sequences
      perform admirably and the better option depends on the priority one puts on the
      quality of the solvent suppression or signal loss due to T2 weighting. Gradient
      based solvent suppression in PGSTE experiments can often be compromised by the
      variable, diffusion-encoding gradient pulses. Special emphasis is put on how to
      maximise the robustness of the solvent suppression. 

PMID- 24926915
TI  - Nitrate anion templated synthesis of a [2]catenane for nitrate recognition in
      organic-aqueous solvent media.
AB  - The first example of a catenane synthesised using a nitrate anion template is
      demonstrated. Removal of the templating anion reveals a mechanically interlocked
      molecular host system which is capable of recognising nitrate selectively over a
      range of more basic mono-anionic oxoanions in a competitive organic-aqueous
      solvent mixture. 

PMID- 24926916
TI  - Effects of surface-passivating ligands and ultrasmall CdSe nanocrystal size on
      the delocalization of exciton confinement.
AB  - Here we report an unprecedentedly large and controllable decrease in the optical
      band gap (up to 107 nm, 610 meV) of molecule-like ultrasmall CdSe nanocrystals
      (diameters ranging from 1.6 to 2.0 nm) by passivating their surfaces with
      conjugated ligands (phenyldithiocarbamates, PDTCs) containing a series of
      electron-donating and -withdrawing functional groups through a ligand-exchange
      reaction on dodecylamine (DDA)-coated nanocrystals. This band-edge absorption
      shift is due to the delocalization of the strongly confined excitonic hole from
      nanocrystals to the ligand molecular orbitals and not from nanocrystal growth or
      dielectric constant effects. (1)H NMR analysis confirmed that the nanocrystal
      surface contained a mixed ligation of DDA and PDTC. The effects of the
      nanocrystal size on the extent of exciton delocalization were also studied and
      found to be smaller for larger nanocrystals. Modulating the energy level of
      ligand-passivated ultrasmall nanocrystals and controlling the electronic
      interaction at the nanocrystal-passivating ligand interface are very important to
      the fabrication of solid-state devices. 

PMID- 24926917
TI  - Association between environmental tobacco smoke and periodontal disease: a
      systematic review.
AB  - The aim of the present study was to systematically review the association between
      environmental tobacco smoke (ETS) and periodontal disease. The addressed focused
      question was "Is there a relationship between ETS and periodontal disease?"
      PubMed/MEDLINE and Google-Scholar databases were searched from 1987 up to March
      2014 using different combinations of the following keywords: "Environmental
      tobacco smoke", "passive", "periodontal disease", "secondhand" and "smoking".
      Letters to the Editor, review articles, commentaries, case-reports and articles
      published in languages other than English were excluded. Thirteen studies were
      included. Nine studies were clinical and 4 studies were performed in-vitro. Five
      studies reported the odds ratios for periodontal disease to be significantly
      higher among individuals exposed to ETS than controls (non-smoking individuals
      unexposed to ETS). In 2 studies, ETS exposure showed no association with
      periodontal disease. In 2 studies, salivary aspartate aminotransferase,
      lactoferrin and albumin levels were reported to be significantly higher in
      individuals exposed to ETS than controls. In one study, levels of salivary
      interleukin-1beta were reported to be significantly higher in individuals exposed
      to ETS than controls. The in-vitro studies reported ETS exposure to enhance the
      production of proinflammatory proteins and phagocytic activity of salivary
      polymorphonuclear leukocytes thereby contributing to periodontal disease. The
      association between ETS and periodontal disease remains debatable and requires
      further investigations. 

PMID- 24926918
TI  - Natural vs synthetic auxin: studies on the interactions between plant hormones
      and biological membrane lipids.
AB  - Analysis of the interactions between two representatives of plant hormones:
      synthetic (1-naphthaleneacetic acid, NAA) as well as natural (indole-3-acetic
      acid, IAA) and phospholipids occurring in biological membrane of both plant and
      animal cells was the subject of present studies. The aim of undertaken
      experiments was to elucidate the problem of direct influence of these plant
      growth regulators on phosphatidylcholines (PCs) and phosphatidylethanolamines
      (PEs) in monolayers at the air/water solution interface. The studied
      phospholipids differ not only as regards the structure of polar head-groups but
      also in the length of hydrophobic chains as well as their saturation degree.
      These differences result also in the main properties and functions of these
      phospholipids in biomembranes. The analysis of the results was based on the
      characteristics of the surface pressure (pi)--area (A) isotherms registered for
      monolayers spread on the subphase containing plant hormone and as a reference on
      the surface of pure water. Moreover, as a complementary technique, Brewster angle
      microscopy was applied for the direct visualization of the investigated surface
      films. The obtained results revealed that auxins effectively influence
      phospholipids monolayers, regardless of the lipid structure, at the concentration
      of 10(-4)M. It was found that for this concentration, the influence of auxins was
      visibly larger in the case of PCs as compared to PEs. On the other hand, in the
      case of auxins solution of <= 10(-5)M, the observed trend was opposite.
      Generally, our studies showed that the natural plant hormone (IAA) interacts with
      the investigated lipid monolayers stronger than its synthetic derivative (NAA).
      The reason of these differences connects with the steric properties of both
      auxins; namely, the naphthalene ring of NAA molecule occupies larger space than
      the indole system of IAA. Therefore molecules of the latter compound penetrate
      easier into the region of phospholipids' polar head-groups. Moreover, the NH
      group of the indole moiety is capable of hydrogen bond formation with the
      acceptor groups in the polar fragment of lipid molecules. We proved also that
      among the investigated phospholipids, the highest susceptibility toward auxin
      influence show these lipids, for which during compression, surface film increases
      the degree of condensation.

PMID- 24926919
TI  - Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a
      population-based sample.
AB  - Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are
      known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl
      hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in
      a population sample were related to genetic variation in the genes encoding these
      CYPs. In the population-based Prospective Investigation of the Vasculature in
      Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1,
      CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by
      high-resolution chromatography coupled to high-resolution mass spectrometry
      (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1,
      CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that
      captures >80% of the variation of all PCBs measured, only the relationship
      between CYP1A1 rs2470893 was significantly related to PCB118 levels following
      strict adjustment for multiple testing (p=0.00011). However, there were several
      additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant
      associations with PCB118 levels (p-values in the 0.003-0.05 range). Further,
      several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p
      values in the 0.005-0.05 range. Very few associations with p<0.05 were seen for
      PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to
      circulating PCB118 levels in the general elderly population. Genetic variation in
      CYP1A2 and CYP1B1 might also be associated with other PCBs. 

PMID- 24926921
TI  - How detection of epigenetic alterations of blood-borne DNA could improve melanoma
      diagnosis.
AB  - Detection in blood of the genetic and epigenetic changes present in metastatic
      cancers is opening up new possibilities in molecular diagnostics. A number of
      methodological and clinical issues await resolution before serum epigenetic
      biomarkers can be considered a routine part of the management of melanoma
      patients following primary excision. However, there is every possibility that
      blood testing for the presence of methylated DNA will become an integral part of
      the clinical follow-up of such patients. The ability to identify patients with
      subclinical (asymptomatic) metastatic melanoma, combined with new, highly active
      targeted and immunomodulatory agents, may lead to further improvements in
      outcomes for this patient population. 

PMID- 24926920
TI  - Fish consumption behavior and rates in native and non-native people in Saudi
      Arabia.
AB  - Fish are a healthy source of protein and nutrients, but contaminants in fish may
      provide health risks. Determining the risk from contaminants in fish requires
      site-specific information on consumption patterns. We examine consumption rates
      for resident and expatriates in the Jeddah region of Saudi Arabia, by species of
      fish and fishing location. For Saudis, 3.7% of males and 4.3% of females do not
      eat fish; for expatriates, the percent not eating fish is 6.6% and 6.1%
      respectively. Most people eat fish at home (over 90%), and many eat fish at
      restaurants (65% and 48%, respectively for Saudis and expatriates). Fish eaten at
      home comes from local fish markets, followed by supermarkets. Saudis included
      fish in their diets at an average of 1.4 +/- 1.2 meals/week at home and 0.8 +/-
      0.7 meals/week at restaurants, while expats ate 2.0 +/- 1.7 meals/week at home
      and 1.1 +/- 1.1 meals/week in restaurants. Overall, Saudis ate 2.2 fish
      meals/week, while expats ate 3.1 meals/week. Grouper (Epinephelus and
      Cephalopholis) were eaten by 72% and 60% respectively. Plectropomus pessuliferus
      was the second favorite for both groups and Hipposcarus harid and Lethrinus
      lentjan were in 3rd and 4th place in terms of consumption. Average meal size was
      68 g for Saudis and 128 g for expatriates. These data can be used by health
      professionals, risk assessors, and environmental regulators to examine potential
      risk from contaminants in fish, and to compare consumption rates with other
      sites.

PMID- 24926922
TI  - An electrospun nanowire-based triboelectric nanogenerator and its application in
      a fully self-powered UV detector.
AB  - A new kind of triboelectric nanogenerator (TENG) is developed based on
      electrospun PVDF and nylon nanowires. This nanogenerator exhibits the remarkable
      characteristics of easy fabrication, low cost and high output. Its open-circuit
      voltage and short-circuit current density respectively reach up to 1163 V and
      11.5 MUA cm(-2) driven by the vibration with a triggering frequency of 5 Hz and
      an amplitude of 20 mm. The peak power density is 26.6 W m(-2). It directly
      powered a DC motor without an energy storage system for the first time. By
      harvesting energy from the environment using this TENG, a fully self-powered UVR
      detection device is developed to show the level of UVR directly without
      additional components. 

PMID- 24926923
TI  - Janus-compartmental alginate microbeads having polydiacetylene liposomes and
      magnetic nanoparticles for visual lead(II) detection.
AB  - Janus-compartmental alginate microbeads having two divided phases of sensory
      polydiacetylene (PDA) liposomes and magnetic nanoparticles were fabricated for
      facile sensory applications. The sensory liposomes are composed of PDA for label
      free signal generation and 1,2-dipalmitoyl-sn-glycero-3-galloyl (DPGG) lipids
      whose galloyl headgroup has specific interactions with lead(II). The second phase
      having magnetic nanoparticles is designed for convenient handling of the
      microbeads, such as washing, solvent exchange, stirring, and detection, by
      applying magnetic field. Selective and convenient colorimetric detection of
      lead(II) and efficient removal of lead(II) by alginate matrix at the same time
      are demonstrated. 

PMID- 24926924
TI  - Gastric perforation by a foreign body presenting as a pancreatic pseudotumour.
AB  - INTRODUCTION: Foreign body ingestion rarely causes complications, though it can
      pose a significant diagnostic challenge. Perforation, particularly of more
      muscular viscera, can present insidiously with a wide range of differential
      diagnoses. PRESENTATION OF CASE: Here we present a case of 75 year-old woman
      presenting with chest and epigastric pain. Initial imaging suggested a pancreatic
      lesion. Despite appropriate treatment she deteriorated clinically, and following
      urgent laparotomy a duck bone fragment was found to have perforated the lesser
      curvature of the stomach and embedded within the liver causing subhepatic abscess
      formation and associated inflammation. DISCUSSION: There are a number of examples
      of insidious presentations of gastrointestinal perforation. However, we have
      found only one other case of a perforation presenting as a pancreatic
      pseudotumour, and ours is the first to have been successfully managed by removal
      of the foreign body and drainage of the abscess alone. CONCLUSION: A high level
      of suspicion is required to make the correct diagnosis in cases such as these
      where the symptoms are not clear-cut. Thorough review and discussion of imaging
      prior to surgical treatment is essential to prevent unnecessary intervention.

PMID- 24926925
TI  - Cauda equina schwannoma presenting with intratumoral hemorrhage and intracranial
      subarachnoid hemorrhage.
AB  - The authors report the case of a spinal intradural schwannoma presenting with
      intracranial subarachnoid hemorrhage (SAH). Cerebral angiography did not show any
      intracranial lesion; however, MRI revealed two separate tumors in the lower
      segment of the spinal cord. The proximal lesion arising from the conus medullaris
      was well circumscribed and homogeneously enhanced, whereas the tumor in the cauda
      equina revealed hemorrhagic signals on MRI. This case also illustrates an unusual
      presentation of intracranial SAH simultaneously with intratumoral hemorrhage in a
      spinal cord schwannoma. The absence of hemorrhagic changes in the lesion arising
      proximal to the cauda equina region supports the mechanical theory proposed for
      the pathogenesis of hemorrhagic complications in spinal cord tumors. 

PMID- 24926926
TI  - Outcomes following attempted en bloc resection of cervical chordomas in the C-1
      and C-2 region versus the subaxial region: a multiinstitutional experience.
AB  - OBJECT: Chordomas involving the mobile spine are ideally managed via en bloc
      resection with reconstruction to optimize local control and possibly offer cure.
      In the cervical spine, local anatomy poses unique challenges, limiting the
      feasibility of aggressive resection. The authors present a multi-institutional
      series of 16 cases of cervical chordomas removed en bloc. Particular attention
      was paid to clinical outcome, complications, and recurrence. In addition,
      outcomes were assessed according to position of tumor at the C1-2 level versus
      the subaxial (SA) spine (C3-7). METHODS: The authors reviewed cases involving
      patients who underwent en bloc resection of cervical chordoma at 4 large spine
      centers. Patients were included if the lesion epicenter involved the C-1 to C-7
      vertebral bodies. Demographic data and details of surgery, follow-up course,
      exposure to adjuvant therapy, and complications were obtained. Outcome was
      correlated with presence of tumor in C1-2 versus subaxial spine via a Student t
      test. RESULTS: Sixteen patients were identified (mean age at presentation 55 +/-
      14 years). Seven cases (44%) cases involved C1-2, and 16 involved the subaxial
      spine. Median survival did not differ significantly different between the C1-2
      (72 months) and SA (60 months) groups (p = 0.65). A combined (staged
      anteroposterior) approach was used in 81% of the cases. Use of the combined
      approach was significantly more common in treatment of subaxial than C1-2 tumors
      (100% vs 57%, p = 0.04). En bloc resection was attempted via an anterior approach
      in 6% of cases (C1-2: 14.3%; SA: 0%; p = 0.17) and a posterior approach in 13% of
      cases (C1-2: 29%; SA: 0%; p = 0.09). The most commonly reported margin
      classification was marginal (56% of cases), followed by violated (25%) and wide
      (19%). En bloc excision of subaxial tumors was significantly more likely to
      result in marginal margins than excision of C1-2 tumors (C1-2: 29%; SA: 78%; p =
      0.03). C1-2 tumors were associated with significantly higher rates of
      postoperative complications (C1-2: 71%; SA: 22%; p = 0.03). Both local and
      distant tumor recurrence was greatest for C1-2 tumors (local C1-2: 29%; local SA:
      11%; distant C1-2: 14%; distant SA: 0%). Statistical analysis of tumor recurrence
      based on tumor location was not possible due to the small number of cases. There
      was no between-groups difference in exposure to postoperative adjuvant
      radiotherapy. There was no difference in median survival between groups receiving
      proton beam radiotherapy or intensity-modulated radiotherapy versus no radiation
      therapy (p = 0.8). CONCLUSIONS: Compared with en bloc resection of chordomas
      involving the subaxial cervical spine, en bloc resection of chordomas involving
      the upper cervical spine (C1-2) is associated with poorer outcomes, such as less
      favorable margins, higher rates of complications, and increased tumor recurrence.
      Data from this cohort do not support a statistically significant difference in
      survival for patients with C1-2 versus subaxial disease, but larger studies are
      needed to further study survival differences.

PMID- 24926927
TI  - Safety and efficacy of pedicle screw placement using intraoperative computed
      tomography: consecutive series of 1148 pedicle screws.
AB  - OBJECT: A number of imaging techniques have been introduced to minimize the risk
      of pedicle screw placement. Intraoperative CT has been recently introduced to
      assist in spinal instrumentation. The aim of this study was to study the
      effectiveness of intraoperative CT in enhancing the safety and accuracy of
      pedicle screw placement. METHODS: The authors included all cases from December
      2009 through July 2012 in which intraoperative CT scanning was used to confirm
      pedicle screw placement. RESULTS: A total of 203 patients met the inclusion
      criteria. Of 1148 screws, 103 screws (8.97%) were revised intraoperatively in 72
      patients (35.5%): 14 (18.42%) were revised in the cervical spine (C-2 or C-7), 25
      (7.25%) in the thoracic spine, and 64 (8.80%) in the lumbar spine. Compared with
      screws in the thoracic and lumbar regions, pedicle screws placed in the cervical
      region were statistically more likely to be revised (p = 0.0061). Two patients
      (0.99%) required reoperations due to undetected misplacement of pedicle screws.
      CONCLUSIONS: The authors describe one of the first North American experiences
      using intraoperative CT scanning to confirm the placement of pedicle screws.
      Compared with a similar cohort of patients from their institution who had pedicle
      screws inserted via the free-hand technique with postoperative CT, the authors
      found that the intraoperative CT lowers the threshold for pedicle screw revision,
      resulting in a statistically higher rate of screw revision in the thoracic and
      lumbar spine (p < 0.0001). During their 2.5-year experience with the
      intraoperative CT, the authors did not find a reduction in rates of reoperation
      for misplaced pedicle screws.

PMID- 24926928
TI  - Primary malignant peripheral nerve sheath tumor of the spine with acute
      hydrocephalus: a rare clinical entity.
AB  - Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in
      patients without a history of neurofibromatosis; only 18 cases have been reported
      in the English-language literature to this point. The authors report their
      experience with 1 new case of a primary MPNST. A 33-year-old woman presented with
      low-back pain radiating to the right calf that progressed over 1 year. Magnetic
      resonance imaging of the spine revealed an intradural extramedullary lesion at
      the T12-L1 level. The patient was diagnosed with primary MPNST, underwent two
      surgical excisions and radiation therapy, and developed leptomeningeal metastases
      as well as brain metastases. The patient revisited the emergency room with sudden
      loss of consciousness. A brain CT scan displayed bilateral lateral ventricle
      enlargement, for which a ventriculoperitoneal shunt was inserted. These symptoms
      have not been described in any previous report. Primary spinal MPNST is an
      exceedingly rare entity, and the overall prognosis is very poor. To the authors'
      knowledge, no standard of care for primary spinal MPNSTs has yet been
      established. All 19 cases of primary spinal MPNSTs are reviewed, and the authors
      discuss their clinical, radiological, and therapeutic features and outcomes. 

PMID- 24926929
TI  - Arthroplasty for cervical spondylotic myelopathy: similar results to patients
      with only radiculopathy at 3 years' follow-up.
AB  - OBJECT: Cervical arthroplasty has been accepted as a viable option for surgical
      management of cervical spondylosis or degenerative disc disease (DDD). The best
      candidates for cervical arthroplasty are young patients who have radiculopathy
      caused by herniated disc with competent facet joints. However, it remains
      uncertain whether arthroplasty is equally effective for patients who have
      cervical myelopathy caused by DDD. The aim of this study was to compare the
      outcomes of arthroplasty for patients with cervical spondylotic myelopathy (CSM)
      and patients with radiculopathy without CSM. METHODS: A total of 151 consecutive
      cases involving patients with CSM or radiculopathy caused by DDD and who
      underwent one- or two-level cervical arthroplasty were included in this study.
      Clinical outcome evaluations and radiographic studies were reviewed. Clinical
      outcome measurements included the Visual Analog Scale (VAS) of neck and arm pain,
      Japanese Orthopaedic Association (JOA) scores, and the Neck Disability Index
      (NDI) in every patient. For patients with CSM, Nurick scores were recorded for
      evaluation of cervical myelopathy. Radiographic studies included lateral dynamic
      radiographs and CT for detection of the formation of heterotopic ossification .
      RESULTS: Of the 151 consecutive patients with cervical DDD, 125 (82.8%; 72
      patients in the myelopathy group and 53 in the radiculopathy group) had at least
      24 months of clinical and radiographic follow-up. The mean duration of follow-up
      in these patients was 36.4 months (range 24-56 months). There was no difference
      in sex distribution between the 2 groups. However, the mean age of the patients
      in the myelopathy group was approximately 6 years greater than that of the
      radiculopathy group (53.1 vs 47.2 years, p < 0.001). The mean operation time,
      mean estimated blood loss, and the percentage of patients prescribed
      perioperative analgesic agents were similar in both groups (p = 0.754, 0.652, and
      0.113, respectively). There were significant improvements in VAS neck and arm
      pain, JOA scores, and NDI in both groups. Nurick scores in the myelopathy group
      also improved significantly after surgery. In radiographic evaluations, 92.5% of
      patients in the radiculopathy group and 95.8% of those in the radiculopathy group
      retained spinal motion (no significant difference). Evaluation of CT scans showed
      heterotopic ossification in 34 patients (47.2%) in the myelopathy group and 25
      patients (47.1%) in the radiculopathy group (p = 0.995). At a mean of over 3
      years postoperatively, no secondary surgery was reported in either group.
      CONCLUSIONS: The severity of myelopathy improves after cervical arthroplasty in
      patients with CSM caused by DDD. At 3-year follow-up, the clinical and
      radiographic outcomes of cervical arthroplasty in DDD patients with CSM are
      similar to those patients who have only cervical radiculopathy. Therefore,
      cervical arthroplasty is a viable option for patients with CSM caused by DDD who
      require anterior surgery. However, comparison with the standard surgical
      treatment of anterior cervical discectomy and fusion is necessary to corroborate
      the outcomes of arthroplasty for CSM.

PMID- 24926930
TI  - A comparative analysis of minimally invasive and open spine surgery patient
      education resources.
AB  - OBJECT: The Internet has become a widespread source for disseminating health
      information to large numbers of people. Such is the case for spine surgery as
      well. Given the complexity of spinal surgeries, an important point to consider is
      whether these resources are easily read and understood by most Americans. The
      average national reading grade level has been estimated to be at about the 7th
      grade. In the present study the authors strove to assess the readability of open
      spine surgery resources and minimally invasive spine surgery resources to offer
      suggestions to help improve the readability of patient resources. METHODS: Online
      patient education resources were downloaded in 2013 from 50 resources
      representing either traditional open back surgery or minimally invasive spine
      surgery. Each resource was assessed using 10 scales from Readability Studio
      Professional Edition version 2012.1. RESULTS: Patient education resources
      representing traditional open back surgery or minimally invasive spine surgery
      were all found to be written at a level well above the recommended 6th grade
      level. In general, minimally invasive spine surgery materials were written at a
      higher grade level. CONCLUSIONS: The readability of patient education resources
      from spine surgery websites exceeds the average reading ability of an American
      adult. Revisions may be warranted to increase quality and patient comprehension
      of these resources to effectively reach a greater patient population.

PMID- 24926931
TI  - Cervical spine injury from gunshot wounds.
AB  - OBJECT: Gunshot wounds (GSWs) to the cervical spine have been examined in a
      limited number of case series, and operative management of this traumatic disease
      has been sparsely discussed. The current literature supports and the authors
      hypothesize that patients without neurological deficit need neither surgical
      fusion nor decompression. Patients with GSWs and neurological deficits, however,
      pose a greater management challenge. The authors have compiled the experience of
      the R Adams Cowley Shock Trauma Center in Baltimore, Maryland, over the past 12
      years, creating the largest series of such injuries, with a total number of 40
      civilian patients needing neurosurgical evaluation. The current analysis examines
      presenting bone injury, surgical indication, presenting neurological examination,
      and neurological outcome. In this study, the authors characterize the incidence,
      severity, and recovery potential of cervical GSWs. The rate of unstable fractures
      requiring surgical intervention is documented. A detailed discussion of surgical
      indications with a treatment algorithm for cervical instability is offered.
      METHODS: A total of 144 cervical GSWs were retrospectively reviewed. Of these
      injuries, 40 had documented neurological deficits. No neurosurgical consultation
      was requested for patients without deficit. Epidemiological and clinical
      information was collected on patients with neurological deficit, including age,
      sex, timing, indication, type of surgery, initial examination after
      resuscitation, follow-up examination, and imaging data. RESULTS: Twenty-eight
      patients (70%) presented with complete neurological deficits and 12 patients
      (30%) presented with incomplete injuries. Fourteen (35%) of the 40 patients
      underwent neurosurgical intervention. Twelve patients (30%) required intervention
      for cervical instability. Seven patients required internal fixation involving 4
      anterior fusions, 2 posterior fusions, and 1 combined approach. Five patients
      were managed with halo immobilization. Two patients underwent decompression alone
      for neurological deterioration and persistent compressive injury, both of whom
      experienced marked neurological recovery. Follow-up was obtained in 92% of cases.
      Three patients undergoing stabilization converted at least 1 American Spinal
      Injury Association (ASIA) Impairment Scale (AIS) grade and the remaining
      operative cases experienced small ASIA motor score improvement. Eighteen patients
      underwent inpatient MRI. No patient suffered complications or neurological
      deterioration related to retained metal. Three of 28 patients presenting with AIS
      Grade A improved to Grade B. For those 12 patients with incomplete injury, 1
      improved from AIS Grade C to D, and 3 improved from Grade D to E. CONCLUSIONS:
      Spinal cord injury from GSWs often results in severe neurological deficits. In
      this series, 30% of these patients with deficits required intervention for
      instability. This is the first series that thoroughly documents AIS improvement
      in this patient population. Adherence to the proposed treatment algorithm may
      optimize neurological outcome and spine stability.

PMID- 24926932
TI  - In vivo 3D kinematic changes in the cervical spine after laminoplasty for
      cervical spondylotic myelopathy.
AB  - OBJECT: Cervical laminoplasty is an effective procedure for decompressing the
      spinal cord at multiple levels, but restriction of neck motion is one of the well
      known complications of the procedure. Although many authors have reported on
      cervical range of motion (ROM) after laminoplasty, they have focused mainly on 2D
      flexion and extension on lateral radiographs, not on 3D motion (including coupled
      motion) nor on precise intervertebral motion. The purpose of this study was to
      clarify the 3D kinematic changes in the cervical spine after laminoplasty
      performed to treat cervical spondylotic myelopathy. METHODS: Eleven consecutive
      patients (6 men and 5 women, mean age 68.1 years, age range 57-79 years) with
      cervical spondylotic myelopathy who had undergone laminoplasty were included in
      the study. All patients underwent 3D CT of the cervical spine in 5 positions
      (neutral, 45 degrees  head rotation left and right, maximum head flexion, and
      maximum head extension) using supporting devices. The scans were performed
      preoperatively and at 6 months after laminoplasty. Segmental ROM from Oc-C1 to C7
      T1 was calculated both in flexion-extension and in rotation, using a voxel-based
      registration method. RESULTS: Mean C2-7 flexion-extension ROM, equivalent to
      cervical ROM in all previous studies, was 45.5 degrees  +/- 7.1 degrees 
      preoperatively and 35.5 degrees  +/- 8.2 degrees  postoperatively, which was a
      statistically significant 33% decrease. However, mean Oc-T1 flexion-extension
      ROM, which represented total cervical ROM, was 71.5 degrees  +/- 8.3 degrees 
      preoperatively and 66.5 degrees  +/- 8.3 degrees  postoperatively, an
      insignificant 7.0% decrease. In focusing on each motion segment, the authors
      observed a statistically significant 22.6% decrease in mean segmental ROM at the
      operated levels during flexion-extension and a statistically insignificant 10.2%
      decrease during rotation. The most significant decrease was observed at C2-3.
      Segmental ROM at C2-3 decreased 24.2% during flexion-extension and 21.8% during
      rotation. However, a statistically insignificant 37.2% increase was observed at
      the upper cervical spine (Oc-C2) during flexion-extension. The coupling pattern
      during rotation did not change significantly after laminoplasty. CONCLUSIONS: In
      this first accurate documentation of 3D segmental kinematic changes after
      laminoplasty, Oc-T1 ROM, which represented total cervical ROM, did not change
      significantly during either flexion-extension or rotation by 6 months after
      laminoplasty despite a significant decrease in C2-7 flexion-extension ROM. This
      is thought to be partially because of a compensatory increase in segmental ROM at
      the upper cervical spine (Oc-C2).

PMID- 24926933
TI  - En bloc hemisacrectomy and internal hemipelvectomy via the posterior approach.
AB  - OBJECT: Traditionally, hemisacrectomy and internal hemipelvectomy procedures have
      required both an anterior and a posterior approach. A posterior-only approach has
      the potential to complete an en bloc tumor resection and spinopelvic
      reconstruction while reducing surgical morbidity. METHODS: The authors describe 3
      cases in which en bloc resection of the hemisacrum and ilium and subsequent
      lumbopelvic and pelvic ring reconstruction were performed from a posterior-only
      approach. Two more traditional anterior and posterior staged procedures are also
      included for comparison. RESULTS: In all 3 cases, an oncologically appropriate
      surgery and spinopelvic reconstruction were performed through a posterior-only
      approach. CONCLUSIONS: The advantage of a midline posterior approach is the
      ability to perform a lumbosacral reconstruction, necessary in cases in which the
      S-1 body is iatrogenically disrupted during tumor resection.

PMID- 24926934
TI  - Computed tomography and pedicle screws.

PMID- 24926935
TI  - Characteristics and surgical results of the distal type of cervical spondylotic
      amyotrophy.
AB  - OBJECT: Cervical spondylosis that causes upper-extremity muscle atrophy without
      gait disturbance is called cervical spondylotic amyotrophy (CSA). The distal type
      of CSA is characterized by weakness of the hand muscles. In this retrospective
      analysis, the authors describe the clinical features of the distal type of CSA
      and evaluate the results of surgical treatment. METHODS: The authors performed a
      retrospective review of 17 consecutive cases involving 16 men and 1 woman (mean
      age 56.3 years) who underwent surgical treatment for the distal type of CSA. The
      condition was diagnosed on the basis of cervical spondylosis in the presence of
      muscle impairment of the upper extremity (intrinsic muscle and/or finger
      extension muscles) without gait disturbance, and the presence of a compressive
      lesion involving the anterior horn of the spinal cord, the nerve root at the
      foramen, or both sites as seen on axial and sagittal views of MRI or CT
      myelography. The authors assessed spinal cord or nerve root impingement by MRI or
      CT myelography and evaluated surgical outcomes. RESULTS: The preoperative
      duration of symptoms averaged 11.8 months. There were 14 patients with
      impingement of the anterior horn of the spinal cord and 3 patients with both
      anterior horn and nerve root impingement. Twelve patients were treated with
      laminoplasty (plus foraminotomy in 1 case), 3 patients were treated with anterior
      cervical discectomy and fusion, and 2 patients were treated with posterior spinal
      fixation. The mean manual muscle testing grade was 2.4 (range 1-4) preoperatively
      and 3.4 (range 1-5) postoperatively. The surgical results were excellent in 7
      patients, good in 2, and fair in 8. CONCLUSIONS: Most of the patients in this
      series of cases of the distal type of CSA suffered from impingement of the
      anterior horn of the spinal cord, and surgical outcome was fair in about half of
      the cases.

PMID- 24926936
TI  - Isolated central canal rupture of spinal dermoid. Report of 3 cases.
AB  - Spinal dermoid tumors are rare, benign, slow-growing tumors. Rupture of spinal
      dermoids, in contrast to cranial dermoids, is rarely reported. Rupture in the
      central canal alone is even more rare, with only a few cases reported in the
      literature. The presence of fat droplets within the central canal is unusual
      because the central canal is rudimentary in adults. The authors report 3 such
      cases and review the pertinent literature. 

PMID- 24926937
TI  - The emergence of "groupitizing" in children's numerical cognition.
AB  - Improvements in enumeration abilities that emerge over late childhood are
      primarily thought to reflect perceptual developments such as increases in
      subitizing limits for small sets and faster shifting of attention associated with
      serially counting larger sets. Contributions of conceptual knowledge development,
      such as the growing appreciation of how whole numbers are composed of subsets of
      whole numbers, are not as well understood. This study examined the emergence of a
      process referred to as "groupitizing," which captures how children may capitalize
      on grouping information to facilitate enumeration processes. We examined
      enumeration speed in a cross-sectional sample of children (N=378), spanning
      kindergarten through third grade, using arrays of dots. Arrays were either
      unstructured or grouped by proximity into subsets in the subitizing range (i.e.,
      three subgroups of 1-3 items). Kindergarten children showed no evidence of
      grouping structure on enumeration. First-grade children enumerated grouped arrays
      faster than unstructured arrays. This structure effect grew progressively
      stronger in subsequent grades. Enumeration speed for unstructured arrays
      increased with set size, yet for grouped arrays the impact of set size was
      dependent on grade level. For kindergartners, the grouping manipulation had no
      impact on the effect of set size. For older children, the grouping manipulation
      reduced the effect of set size on enumeration. Furthermore, individual
      differences in how set size affected enumeration of grouped arrays showed unique
      patterns of association with performance on standardized symbolic arithmetic
      fluency tests, suggesting a unique role for the construct of groupitizing in the
      development of enumeration fluency and symbolic math skills. 

PMID- 24926938
TI  - Synthesis of beta-Mg(2)C(3): a monoclinic high-pressure polymorph of magnesium
      sesquicarbide.
AB  - A new monoclinic variation of Mg2C3 was synthesized from the elements under high
      pressure (HP), high-temperature (HT) conditions. Formation of the new compound,
      which can be recovered to ambient conditions, was observed in situ using X-ray
      diffraction with synchrotron radiation. The structural solution was achieved by
      utilizing accurate theoretical results obtained from ab initio evolutionary
      structure prediction algorithm USPEX. Like the previously known orthorhombic Pnnm
      structure (alpha-Mg2C3), the new monoclinic C2/m structure (beta-Mg2C3) contains
      linear C3(4-) chains that are isoelectronic with CO2. Unlike alpha-Mg2C3, which
      contains alternating layers of C3(4-) chains oriented in opposite directions, all
      C3(4-) chains within beta-Mg2C3 are nearly aligned along the crystallographic c
      axis. Hydrolysis of beta-Mg2C3 yields C3H4, as detected by mass spectrometry,
      while Raman and NMR measurements show clear C?C stretching near 1200 cm(-1) and
      (13)C resonances confirming the presence of the rare allylenide anion. 

PMID- 24926939
TI  - Effects of work zone configurations and traffic density on performance variables
      and subjective workload.
AB  - This paper investigates the effect of changing work zone configurations and
      traffic density on performance variables and subjective workload. Data regarding
      travel time, average speed, maximum percent braking force and location of lane
      changes were collected by using a full size driving simulator. The NASA-TLX was
      used to measure self-reported workload ratings during the driving task.
      Conventional lane merge (CLM) and joint lane merge (JLM) were modeled in a
      driving simulator, and thirty participants (seven female and 23 male), navigated
      through the two configurations with two levels of traffic density. The mean
      maximum braking forces was 34% lower in the JLM configuration, and drivers going
      through the JLM configuration remained in the closed lane longer. However, no
      significant differences in speed were found between the two merge configurations.
      The analysis of self-reported workload ratings show that participants reported
      15.3% lower total workload when driving through the JLM. In conclusion, the
      implemented changes in the JLM make it a more favorable merge configuration in
      both high and low traffic densities in terms of optimizing traffic flow by
      increasing the time and distance cars use both lanes, and in terms of improving
      safety due to lower braking forces and lower reported workload. 

PMID- 24926940
TI  - Photoprotective effect of arctiin against ultraviolet B-induced damage in HaCaT
      keratinocytes is mediated by microRNA expression changes.
AB  - Human keratinocytes are located in the outermost skin layer and thus particularly
      vulnerable to ultraviolet B (UVB) radiation exposure. Previous studies have
      focused on the cellular and molecular perspectives of UVB-induced keratinocyte
      damage. In the present study, it was demonstrated that pretreatment with the
      phytochemical arctiin, one of the lignin compounds, protects human HaCaT
      keratinocytes from UVB-mediated damage. Biochemical assays revealed that UVB
      induced cytotoxicity and cell death were significantly reduced in arctiin
      pretreated HaCaT cells. In addition, arctiin promoted the wound healing and DNA
      repair properties of keratinocytes. The photoprotective effects of arctiin were
      associated with changes in the expression levels of specific microRNAs (miRNAs)
      in HaCaT cells. A bioinformatics analysis demonstrated that the miRNAs were
      functionally involved in cancer, cell cycle, and Wnt and mitogen-activated
      protein kinase signaling pathways. In the present study, the results from the
      cellular and molecular assays demonstrated a novel role for arctiin in UVB
      protection in keratinocytes, which is mediated by miRNA responses and the
      suppression of UVB-induced cell death. Furthermore, arctiin is implicated as a
      potential chemopreventive agent through UVB protection of keratinocytes. 

PMID- 24926941
TI  - Enhancing trial integrity by protecting the independence of data monitoring
      committees in clinical trials.
AB  - Data monitoring committees (DMCs) have important roles in safeguarding patient
      interests and enhancing trial integrity and credibility. To effectively fulfill
      their responsibilities, DMCs should be independent of study sponsors, study
      investigators, and caregivers managing study participants. Unfortunately, in real
      world settings where DMCs are in place, there are some practices that threaten to
      diminish the level of independence of these committees. To address this, some
      important approaches should be considered: A DMC charter should outline the roles
      and responsibilities of the DMC without appearing to be a legal contract; the
      meetings of the DMC should be led by its chair, ideally with a meeting format
      that ensures independence from the investigators and sponsor; the DMC and those
      having leadership roles in the monitoring process should have adequate training
      and experience; procedures should be in place to enable the DMC to have access to
      interim safety and efficacy data that are accurate, current, and comprehensive;
      these data should be presented to the DMC unblinded by treatment group, while
      being kept confidential from all others; DMC recommendations should be developed
      through consensus development rather than by casting votes; creative approaches
      are needed for the engagement of DMC members to increase the transparency such
      that they are neither employees of nor consultants to the sponsor of the trial;
      meaningful conflicts of interest should be identified and addressed; and finally,
      members of DMCs should have adequate indemnification that provides effective
      protection. 

PMID- 24926942
TI  - The relationship of depression to antiepileptic drug adherence and quality of
      life in epilepsy.
AB  - We sought to examine the impact of depression upon antiepileptic drug (AED)
      adherence in patients with epilepsy. We administered the Center for Epidemiologic
      Studies Depression Scale (CES-D), Neurological Disorders Depression Inventory for
      Epilepsy (NDDI-E), Seizure Severity Questionnaire (SSQ), and Quality of Life in
      Epilepsy-10 (QOLIE-10) and measured AED adherence by utilizing the medication
      possession ratio (MPR) in adult patients with epilepsy identified through a
      pharmacy claims database. From a sampling frame of over 10,000 patients
      identified in claims, 2750 were randomly selected and contacted directly by mail
      to participate in the cross-sectional survey. A total of 465 eligible patients
      completed a survey. Survey data were combined with administrative claims data for
      analysis. We conducted a path analysis to assess the relationships between
      depression, adherence, seizure severity, and quality of life (QOL). Patients with
      depression scored significantly worse on measures of seizure severity (p=.003),
      QOL (p<.001), and adherence (p=.001). On path analysis, depression and QOL and
      seizure severity and QOL were related, but only the NDDI-E scores had a
      significant relationship with medication adherence (p=.001). Depression as
      measured by the NDDI-E was correlated with an increased risk of AED nonadherence.
      Depression or seizure severity adversely impacted QOL. These results demonstrate
      yet another important reason to screen for depression in epilepsy. 

PMID- 24926943
TI  - Longitudinal analysis of hippocampal T2 relaxometry in FMTLE.
AB  - PURPOSE: To investigate the degree of T2 relaxometry changes over time in groups
      of patients with familial mesial temporal lobe epilepsy (FMTLE) and asymptomatic
      relatives. METHODS: We conducted both cross-sectional and longitudinal analyses
      of T2 relaxometry with Aftervoxel, an in-house software for medical image
      visualization. The cross-sectional study included 35 subjects (26 with FMTLE and
      9 asymptomatic relatives) and 40 controls; the longitudinal study was composed of
      30 subjects (21 with FMTLE and 9 asymptomatic relatives; the mean time interval
      of MRIs was 4.4 +/- 1.5 years) and 16 controls. To increase the size of our
      groups of patients and relatives, we combined data acquired in 2 scanners (2T and
      3T) and obtained z-scores using their respective controls. General linear model
      on SPSS21(r) was used for statistical analysis. RESULTS: In the cross-sectional
      analysis, elevated T2 relaxometry was identified for subjects with seizures and
      intermediate values for asymptomatic relatives compared to controls. Subjects
      with MRI signs of hippocampal sclerosis presented elevated T2 relaxometry in the
      ipsilateral hippocampus, while patients and asymptomatic relatives with normal
      MRI presented elevated T2 values in the right hippocampus. The longitudinal
      analysis revealed a significant increase in T2 relaxometry for the ipsilateral
      hippocampus exclusively in patients with seizures. CONCLUSIONS: The longitudinal
      increase of T2 signal in patients with seizures suggests the existence of an
      interaction between ongoing seizures and the underlying pathology, causing
      progressive damage to the hippocampus. The identification of elevated T2
      relaxometry in asymptomatic relatives and in patients with normal MRI suggests
      that genetic factors may be involved in the development of some mild hippocampal
      abnormalities in FMTLE.

PMID- 24926944
TI  - Large scale production of 51Cr for medical application in a medium flux research
      reactor: a comparative investigation of Szilard-Chalmers process and direct
      (n,gamma) route.
AB  - The present article reports a systematic assessment on the reactor production of
      (51)Cr using the Szilard-Chalmers process as well as (50)Cr(n,gamma)(51)Cr
      routes. In an attempt to select the most convenient path to undertake large-scale
      production of (51)Cr, the effectiveness of both the production routes on the
      basis of target selection, irradiated target processing, yield and specific
      activity of (51)Cr, was evaluated. An optimized (50)Cr(n,gamma)(51)Cr production
      scheme offering (51)Cr of requisite purity is the positive outcome. 

PMID- 24926945
TI  - Evaluation of different production routes for the radio medical isotope 203Pb
      using TALYS 1.4 and EMPIRE 3.1 code calculations.
AB  - (203)Pb radio-medical isotope has found great field of applications in nuclear
      medicine over the last decades. The previously measured excitation functions for
      the production of this isotope from different reactions were discussed, in order
      to confirm the most reasonable ones. Fitting curves were given for some reactions
      leading to the production of this isotope. The theoretical models TALYS 1.4, and
      EMPIRE 3.1 were used to construct the excitation functions for protons,
      deuterons, helium-3 and helium-4 induced reactions on Tl and Hg targets. The
      results of different models were compared with each other as well as with the
      collected experimental results, using the mean weighted deviation (F), and the
      relative variance (D) statistical parameters. Thick target yields were estimated,
      based on the discussed excitation functions, and compared with some measured
      values. 

PMID- 24926946
TI  - Activation cross sections of alpha-particle induced nuclear reactions on hafnium
      and deuteron induced nuclear reaction on tantalum: production of 178W/(178m)Ta
      generator.
AB  - In the frame of a systematic study of charged particle production routes of
      medically relevant radionuclei, the excitation function for indirect production
      of (178m)Ta through (nat)Hf(alpha,xn)(178)W-(178m)Ta nuclear reaction was
      measured for the first time up to 40 MeV. In parallel, the side reactions
      (nat)Hf(alpha,x)(179,177,176,175)W, (183,182,178g,177,176,175)Ta,
      (179m,177m,175)Hf were also assessed. Stacked foil irradiation technique and
      gamma-ray spectrometry were used. New experimental cross section data for the
      (nat)Ta(d,xn)(178)W reaction are also reported up to 40 MeV. The measured
      excitation functions are compared with the results of the ALICE-IPPE, and EMPIRE
      nuclear reaction model codes and with the TALYS 1.4 based data in the TENDL-2013
      library. The thick target yields were deduced and compared with yields of other
      charged particle ((p,4n), (d,5n) and ((3)He,x)) production routes for (178)W.

PMID- 24926947
TI  - Ternary complex formation and IGFBP-3 proteolytic activity during childhood: age
      dependent changes.
AB  - BACKGROUND: IGF-I is mainly sequestered in a 150-kDa ternary complex with IGF
      binding protein (IGFBP)-3 and the acid-labile subunit. Data on complex formation
      and factors influencing formation have not been established. Dissociation of IGF
      I from the ternary complex is in part regulated by proteolysis of IGFBP-3, which
      reduces its affinity for IGF-I. Short small for gestational age (SGA) children
      have lower IGF-I and IGFBP-3 levels compared with healthy peers. OBJECTIVE: The
      objective of the study was to determine complex formation in healthy normal
      statured children and assess variables influencing complex formation. Second, we
      determined complex formation in short SGA children. DESIGN/METHODS: Complex
      formation was assessed using (125)I-hIGF-I column chromatography in 70 controls
      (40 boys), median age 10.6 years, and 40 short SGA children (25 boys), median age
      8.6 years. IGFBP-3 was determined by Western immunoblotting. RESULTS: (125)I-hIGF
      I complex formation showed an age-specific pattern in healthy controls. Variables
      positively influencing ternary complex formation were higher serum IGF-I levels
      compared with IGFBP-3 levels (P < .001) and lower serum IGF-II (P < .001) and
      IGFBP-1 levels (P < .001). In addition, a higher presence of proteolyzed IGFBP-3
      negatively influenced 150-kDa complex formation (P = .006). At a young age,
      healthy children showed considerable IGFBP-3 proteolytic activity, which declined
      with aging (P < .001). IGFBP-3 proteolytic activity was negatively correlated
      with IGF-I levels (P < .001). Compared with healthy controls, short SGA children
      showed reduced IGF-I levels (-1.3 vs 0.1 SD score) and increased proteolyzed
      IGFBP-3 (35.1% vs 12.2%). CONCLUSION: Age-specific normative values for (125)I
      hIGF-I 150-kDa ternary complex formation are presented. A decrease in IGF-I and
      an increase in IGF-II, IGFBP-1, and IGFBP-3 proteolytic activity associate with
      reduced (125)I-hIGF-I ternary complex formation. Our results suggest that in
      conditions in which IGF-I levels are low, such as young age and in short SGA
      children, IGFBP-3 proteolytic activity is increased to ensure IGF-I
      bioavailability.

PMID- 24926948
TI  - Adiposity, chronic inflammation, and the prepubertal decline of sex hormone
      binding globulin in children: evidence for associations with the timing of
      puberty (Earlybird 58).
AB  - BACKGROUND: The regulation and role of SHBG in children are poorly defined. Here
      we investigated whether adiposity-related mechanisms regulate SHBG and whether
      SHBG levels are associated with the age of puberty. METHODS: Longitudinal
      modelling of annual physiological and endocrine measurements from age 5 to 15
      years in a cohort of 347 Plymouth schoolchildren. RESULTS: SHBG levels were
      highest at age 5 years and then declined. Mean (SE) SHBG levels were higher in
      boys than girls at age 5 years [mean (SE) difference 7.68 (3.80) nmol/L; P =
      .045] but lower in boys by age 15 years [difference 12.19 (3.4) nmol/L; P <
      .001]. SHBG correlated inversely with adiposity [body mass index SD score (BMI
      SDS)], insulin, IGF-I, C-reactive protein (CRP), and leptin and positively with
      adiponectin but not with dehydroepiandrosterone sulphate, androstenedione, or T.
      In linear mixed models, five adiposity-related covariates (insulin, leptin,
      adiponectin, IGF-I, and CRP) all exerted significant main effects on SHBG (boys P
      = .04 to < .001; girls P = .007 to < .001). However, the further addition of BMI
      SDS rendered the effects of leptin, insulin, and adiponectin nonsignificant,
      whereas CRP and IGF-I remained significant. In separate models, the individual
      effects on SHBG of insulin, leptin, IGF-I, and adiponectin, but not CRP, were
      displaced by BMI SDS. Finally, in linear regression, BMI SDS little affected R(2)
      resulting from the five adiposity-related signals. Girls with lower SHBG levels
      at age 5 years reached Tanner stage 2 earlier, tended to have earlier LH
      secretion, and earlier age at peak height velocity and menarche. In contrast,
      boys with lower SHBG levels at age 5 years reached Tanner stage 2 earlier, but
      there were no relationships between SHBG and earlier onset of LH secretion or age
      at peak height velocity. CONCLUSIONS: Adiposity-related endocrine mechanisms and
      chronic inflammation were associated with the prepubertal decline of SHBG, and
      lower SHBG levels anticipated earlier puberty. These findings may be relevant to
      the occurrence of earlier puberty in recent decades.

PMID- 24926949
TI  - Maintenance of optimal vitamin D status in children and adolescents with
      inflammatory bowel disease: a randomized clinical trial comparing two regimens.
AB  - CONTEXT: Vitamin D promotes bone health and regulates the immune system, both
      important actions for pediatric patients with inflammatory bowel disease (IBD).
      The supplementation dose that would maintain optimal serum 25-hydroxyvitamin D
      concentration (25OHD >= 32 ng/mL) is unknown. OBJECTIVE: The objective of the
      study was to compare two supplementation regimens' efficacy and safety in
      maintaining optimal 25OHD in children with IBD. DESIGN: This was a randomized,
      not blinded, controlled trial. SETTING: The trial was conducted in the Boston
      Children's Hospital Clinical and Translational Study Unit. PARTICIPANTS: Sixty
      three patients, aged 8-18 years with IBD and baseline 25OHD greater than 20 ng/mL
      were enrolled; 48 completed the study, and one withdrew for adverse events.
      INTERVENTION: Arm A received 400 IU of oral vitamin D2 daily (n = 32). Arm B
      received 1000 IU daily in the summer/fall and 2000 IU in the winter/spring (n =
      31). MAIN OUTCOME: The main outcome was the probability of maintaining 25OHD of
      32 ng/mL or greater in all trimonthly visits for 12 months. RESULTS: Three
      participants in arm A (9.4%) and three in arm B (9.7%) achieved the primary
      outcome (P = .97). The incidence of adverse events, all minor, did not differ.
      More participants in arm A developed C-reactive protein level of 1 mg/dL or
      greater (31% vs 10%, P = .04) and IL-6 greater than 3 pg/mL (54% vs 27%, P =
      .05). CONCLUSIONS: Daily oral vitamin D2 doses up to 2000 IU were inadequate to
      maintain optimal 25OHD but were well tolerated. The finding of lower incidence of
      elevated inflammatory markers and cytokines among participants receiving higher
      vitamin D2 doses merits further study.

PMID- 24926950
TI  - 36-month treatment experience of two doses of leuprolide acetate 3-month depot
      for children with central precocious puberty.
AB  - CONTEXT: We have recently demonstrated short-term (6-month) efficacy and safety
      of leuprolide acetate 3-month depot 11.25 and 30 mg in children with central
      precocious puberty (CPP). OBJECTIVE: To assess long-term (36-month) hypothalamic
      pituitary-gonadal axis suppression and safety of leuprolide acetate 3-month depot
      11.25 and 30 mg in children with CPP. DESIGN: Open-label, 36-month extension.
      SETTING: Twenty pediatric endocrine centers. PATIENTS: Seventy-two children (mean
      age, 8.5 +/- 1.6 y; 65 females) with CPP completed and showed maintenance of LH
      suppression after a 6-month lead-in study. INTERVENTION: Leuprolide acetate depot
      (11.25 or 30 mg) administered im every 3 months. MAIN OUTCOME MEASURES: Peak
      stimulated LH, estradiol, T, growth rate, pubertal progression, and adverse
      events (AEs). RESULTS: Twenty-nine of 34 subjects in the 11.25-mg group and 36 of
      38 subjects in the 30-mg group had LH values < 4 mIU/mL after day 1 at all time
      points. All seven subjects who escaped LH suppression at any time still
      maintained sex steroid concentrations at prepubertal levels and showed no signs
      of pubertal progression. AEs were comparable between groups, with injection site
      pain being the most common (26.4% overall). No AE led to discontinuation of study
      drug. The safety profile over 36 months was comparable to that observed during
      the 6-month pivotal study. CONCLUSIONS: The two doses of leuprolide acetate 3
      month depot were associated with an acceptable safety profile and provided
      maintenance of LH suppression in the majority of children with CPP during the 36
      months of the study or until readiness for puberty.

PMID- 24926951
TI  - A comparison of fat and lean body mass index to BMI for the identification of
      metabolic syndrome in children and adolescents.
AB  - CONTEXT: The use of body mass index (BMI) to assess risk for cardiometabolic
      disease in the pediatric population may be limited by a failure to differentiate
      between fat and lean body mass. OBJECTIVES: The objectives of the study were to
      identify biologically based criteria for the definition of obesity using fat
      (FMI) and lean body mass index (LBMI) and to compare the ability of FMI and LBMI
      to BMI to identify the presence of metabolic syndrome (MetSyn). DESIGN: This was
      a cross-sectional study using National Health and Nutrition Examination Survey
      1999-2006 data. PARTICIPANTS: A total of 3004 participants aged 12-20 years with
      dual-energy X-ray absorptiometry body composition and fasting laboratory data
      participated in the study. MAIN OUTCOME MEASURES: Adjusted odds ratios for MetSyn
      according to FMI and LBMI status and area under the curve for the identification
      of MetSyn were measured. RESULTS: Receiver-operating characteristic curve
      analyses identified the 80th percentile for FMI and the 74th percentile for LBMI
      as the optimal cut points for the identification of MetSyn. There was no
      difference in the area under the curve for FMI [0.867; 95% confidence interval
      (CI) 0.838-0.891] vs BMI (0.868; 95% CI 0.837-0.894) Z-scores for MetSyn
      discrimination. Separate multivariate regression models identified odds ratios
      for the identification of MetSyn of 6.2 (95% CI 3.3-11.5) for BMI-Z, 6.4 (95% CI
      3.7-11.1) for FMI-Z, and 4.6 (95% CI 3.0-7.1) for LBMI-Z. Models containing both
      FMI-Z and LBMI-Z revealed that greater LBMI-Z was associated with greater odds of
      low high-density lipoprotein (1.5; 95% CI 1.2-1.9), high blood pressure (1.8; 95%
      CI 1.1-2.9), and insulin resistance (1.8; 95% CI 1.4-2.5), independent of FMI-Z.
      CONCLUSIONS: The use of FMI and LBMI does not improve upon BMI for the
      identification of MetSyn in the pediatric population. Unexpectedly, higher LBMI
      was associated with greater odds of multiple cardiometabolic risk factors
      independent of FMI. The use of FMI and LBMI allow for the independent evaluation
      of relationships between body compartments and disease and warrants future
      research.

PMID- 24926952
TI  - Association of adenovirus 36 infection with adiposity and inflammatory-related
      markers in children.
AB  - CONTEXT: Although animal studies suggest that adenovirus 36 (Ad36) infection is
      linked to obesity and systemic inflammation, human data are scant and equivocal.
      OBJECTIVE: Associations of Ad36 infection with total body adiposity and
      inflammatory-related markers were determined in 291 children aged 9-13 years (50%
      female, 49% black). DESIGN: Fasting blood samples were measured for presence of
      Ad36-specific antibodies and TNF-alpha, IL-6, vascular endothelial growth factor
      (VEGF), and monocyte chemoattractant protein-1 (MCP-1). Fat mass and fat-free
      soft tissue mass were measured by dual-energy X-ray absorptiometry. RESULTS: The
      overall prevalence of Ad36 seropositivity [Ad36(+)] was 42%. There was a higher
      percentage of Ad36(+) children in the highest tertiles of TNF-alpha and IL-6
      compared with their respective middle and lowest tertiles (both P < .03). There
      was also a trend toward a higher prevalence of Ad36(+) children in the highest
      tertile of VEGF compared with tertiles 1 and 2 (P = .05). Multinomial logistic
      regression, adjusting for age, race, sex, and fat-free soft tissue mass, revealed
      that compared with children with the lowest TNF-alpha, IL-6, and VEGF levels
      (tertile 1), the adjusted odds ratios for Ad36(+) were 2.2 [95% confidence
      interval (CI) 1.2-4.0], 2.4 (95% CI 1.4-4.0), and 1.8 (95% CI 1.0-3.3),
      respectively, for those in the highest TNF-alpha, IL-6, and VEGF levels (tertile
      3). No association was observed between Ad36(+) and greater levels of fat mass or
      MCP-1 (all P > .05). CONCLUSIONS: In children, our data suggest that Ad36(+) may
      be associated with biomarkers implicated in inflammation but not with greater
      levels of fat mass.

PMID- 24926953
TI  - Lipid regulation in lipodystrophy versus the obesity-associated metabolic
      syndrome: the dissociation of HDL-C and triglycerides.
AB  - CONTEXT: There is an inverse relationship between triglycerides and high-density
      lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in
      insulin resistance decreases triglycerides and increases HDL-C. Patients with
      lipodystrophy have extreme insulin resistance with high triglycerides and low HDL
      C. Leptin replacement in lipodystrophy leads to a marked decrease in
      triglycerides (~60%). OBJECTIVE: Our objective was to study the effects of
      metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in
      triglycerides and HDL-C in interventions for the obesity-associated metabolic
      syndrome. DESIGN, SETTING, AND PATIENTS: This open-label nonrandomized study at
      the National Institutes of Health included 82 patients with various forms of
      lipodystrophy. INTERVENTION: Metreleptin (0.06-0.24 mg/kg/d) was administered for
      24 months in lipodystrophy. MAIN OUTCOME MEASURES: Serum triglycerides and HDL-C
      were measured. RESULTS: At baseline, lipodystrophy patients had low HDL-C (30 +/-
      1 mg/dL) and high triglycerides (961 +/- 220 mg/dL) with an inverse relationship
      between the two (R = -0.37, P = .0006). There was no change in HDL-C with
      metreleptin despite major improvement in triglycerides, and individual changes in
      triglycerides only weakly predicted HDL-C change. On linear regression, in
      obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2
      mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in
      log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C.
      CONCLUSIONS: The normal reciprocal relationship between triglyceride and HDL-C
      change seen in response to interventions for the obesity-associated metabolic
      syndrome is quantitatively different from that seen in lipodystrophy in response
      to metreleptin. Further work is needed to understand HDL-C regulation in this
      condition.

PMID- 24926954
TI  - Effects of intraduodenal infusion of L-tryptophan on ad libitum eating,
      antropyloroduodenal motility, glycemia, insulinemia, and gut peptide secretion in
      healthy men.
AB  - CONTEXT: Changes in gut motor and hormonal function contribute to the eating
      inhibitory and glucose-lowering effects of protein. The effect of amino acids,
      the digestive products of protein, on gastrointestinal function, eating, and
      glycemia has not been investigated comprehensively. OBJECTIVE: We tested the
      hypothesis that L-tryptophan (L-Trp) stimulates gastrointestinal motor and
      hormonal functions, inhibits eating, and modulates glycemia. Design, Settings,
      Participants, and Intervention: Ten healthy, normal-weight men were studied in
      randomized, double-blind fashion, each receiving a 90-minute intraduodenal
      infusion of L-Trp at 0.075 (total 6.75 kcal) or 0.15 (total 13.5 kcal) kcal/min
      or saline (control). MAIN OUTCOME MEASURES: Antropyloroduodenal motility, plasma
      ghrelin, cholecystokinin, glucagon-like peptide-1, peptide tyrosine tyrosine,
      insulin, glucagon, blood glucose, and appetite perceptions were measured. Food
      intake was quantified from a buffet meal after the infusion. RESULTS:
      Intraduodenal L-Trp suppressed antral pressures (P < .05) and stimulated pyloric
      pressures (P < .01) and markedly increased cholecystokinin and glucagon (both P <
      .001). Glucagon-like peptide-1 and peptide tyrosine tyrosine increased modestly
      (both P < .001), but there was no effect on total ghrelin. Insulin increased
      slightly (P < .05) without affecting blood glucose. Plasma L-Trp increased
      substantially (P < .001). All effects were dose-related and associated with
      increased fullness and substantially decreased energy intake (P < .001). There
      was a strong inverse correlation between energy intake and plasma L-Trp (r = 
      0.70; P < .001). CONCLUSIONS: Low caloric intraduodenal loads of L-Trp affect gut
      motor and hormonal function and markedly reduce energy intake. A strong inverse
      correlation between energy intake and plasma L-Trp suggests that, beyond gut
      mechanisms, direct effects of circulating L-Trp mediate its eating-inhibitory
      effect.

PMID- 24926956
TI  - Increased visceral adiposity and cortisol to cortisone ratio in adults with
      congenital lifetime isolated GH deficiency.
AB  - CONTEXT: Adult-onset GH deficiency (GHD) increases visceral adiposity and the
      activity of the enzyme 11beta-hydroxysteroid dehydrogenase, which converts
      cortisone (E) to cortisol (F), both linked to insulin resistance and increased
      cardiovascular risk. Conversely, we reported that adults with congenital isolated
      GHD (IGHD) have increased insulin sensitivity. OBJECTIVE: To assess the type of
      fat distribution and the amount of visceral and sc fat and to correlate them to
      the F/E ratio in adults with untreated IGHD due to a mutation in the GHRH
      receptor gene. METHODS: Body composition was assessed by dual-energy x-ray
      absorptiometry, thickness of sc and visceral fat was measured by sonography, and
      serum F and E were measured in 23 IGHD subjects and 21 age-matched controls.
      RESULTS: Waist/hip ratio (WHR), trunk fat, and trunk/extremity fat (TR/EXT) ratio
      were higher in IGHD subjects. Visceral fat index (VFI) (but not sc fat index
      [SFI]) was higher in IGHD. F and F/E ratio were also higher in IGHD. In all 44
      individuals, WHR correlated with TR/EXT ratio, thickness of visceral fat, VFI/SFI
      ratio, F, and F/E ratio. TR/EXT ratio correlated with visceral fat thickness,
      VFI/SFI ratio, and F. Age had a significant effect on VFI and on F/E ratio. Body
      mass index SD score and WHR have a similar significant effect on TR/EXT ratio and
      on F/E ratio. CONCLUSIONS: Lifetime congenital untreated IGHD causes increased
      visceral adiposity with a high F/E ratio. However, the increased insulin
      sensitivity suggests that visceral adiposity needs a minimal GH secretion to
      translate into increased insulin resistance.

PMID- 24926955
TI  - Compromised bone microarchitecture and estimated bone strength in young adults
      with cystic fibrosis.
AB  - CONTEXT: Young adults with cystic fibrosis (CF) are at risk for low bone density
      and fractures, but the underlying alterations in bone microarchitecture that may
      contribute to their increased fracture risk are currently unknown. OBJECTIVE: The
      main goal of this study was to use high-resolution peripheral quantitative
      computed tomography (HR-pQCT) to characterize the bone microarchitecture,
      volumetric bone mineral density (vBMD), and estimated strength of the radius and
      tibia in young adults with CF compared with healthy volunteers. DESIGN AND
      SETTING: This was a cross-sectional study at an outpatient clinical research
      center within a tertiary academic medical center. PARTICIPANTS: Thirty young
      adults with CF, 18 to 40 years of age, were evaluated and compared with 60
      healthy volunteers matched by age (+/-2 years), gender, and race. MAIN OUTCOME
      MEASURES: The primary outcomes were HR-pQCT-derived cortical and trabecular vBMD,
      bone microarchitecture, and estimates of bone strength. RESULTS: At the radius
      and tibia, young adults with CF had smaller bone cross-sectional area and lower
      vBMD. Cortical and trabecular microarchitecture were compromised at both sites,
      most notably involving the trabecular bone of the tibia. These differences
      translated into lower estimated bone strength both at the radius and tibia. After
      accounting for body mass index differences, young adults with CF had lower bone
      area and estimated bone strength at the radius and had compromised trabecular
      microarchitecture and lower total and trabecular vBMD and estimated bone strength
      at the tibia. Alterations in trabecular bone density and microarchitecture and
      estimated strength measures of the tibia were also greater than expected based on
      dual-energy x-ray absorptiometry-derived areal BMD differences. CONCLUSIONS:
      Young adults with CF have compromised bone microarchitecture and lower estimated
      bone strength at both the radius and tibia, even after accounting for their
      smaller body size. These skeletal deficits likely explain the higher fracture
      risk observed in young adults with CF.

PMID- 24926957
TI  - Specialized home palliative care for adults and children: differences and
      similarities.
AB  - OBJECTIVE: To compare the provision of specialized home palliative care (SHPC) by
      the adult and pediatric SHPC teams at the Munich University Hospital. METHODS:
      All patients treated by one of the SHPC teams and their primary caregivers were
      eligible for the prospective nonrandomized survey. We analyzed the demographics,
      the underlying diseases, duration and impact of SHPC on symptom control and
      quality of life (QOL) as well as the caregivers' burden and QOL. RESULTS: Between
      April 2011 and June 2012, 100 adult and 43 pediatric patients were treated
      consecutively; 60 adults (median age, 67.5 years; 55% male) and 40 children
      (median age, 6 years, 57% male) were included in the study. Oncologic diseases
      were dominant only in the adult cohort (87 versus 25%, p<0.001). The median
      period of care was higher in the pediatric sample (11.8 versus 4.3 weeks; NS).
      Ninety-five percent of adult and 45% of pediatric patients died by the end of the
      study (p<0.001), 75% and 90% of them at home, respectively. The numbers of
      significant others directly affected by the patient's disease was higher in
      children (mean 3.4 versus 1.2; p<0.001). The QOL of adult patients and children
      (p<0.05 for both), as well as of their primary caregivers (p<0.001 for both)
      improved during SHPC, while the caregivers' burden was lowered (p<0.001 for
      both). CONCLUSIONS: Our results show important differences in several clinically
      relevant parameters between adults and children receiving SHPC. This should
      assist in the development of age-group specific SHPC concepts that effectively
      address the specific needs of each patient population.

PMID- 24926958
TI  - Evaluation of common type 2 diabetes risk variants in a South Asian population of
      Sri Lankan descent.
AB  - INTRODUCTION: Most studies seeking common variant associations with type 2
      diabetes (T2D) have focused on individuals of European ancestry. These
      discoveries need to be evaluated in other major ancestral groups, to understand
      ethnic differences in predisposition, and establish whether these contribute to
      variation in T2D prevalence and presentation. This study aims to establish
      whether common variants conferring T2D-risk in Europeans contribute to T2D
      susceptibility in the South Asian population of Sri Lanka. METHODOLOGY: Lead
      single nucleotide polymorphism (SNPs) at 37 T2D-risk loci attaining genome-wide
      significance in Europeans were genotyped in 878 T2D cases and 1523 normoglycaemic
      controls from Sri Lanka. Association testing was performed by logistic regression
      adjusting for age and sex and by the Cochran-Mantel-Haenszel test after
      stratifying according to self-identified ethnolinguistic subgroup. A weighted
      genetic risk score was generated to examine the combined effect of these SNPs on
      T2D-risk in the Sri Lankan population. RESULTS: Of the 36 SNPs passing quality
      control, sixteen showed nominal (p<0.05) association in Sri Lankan samples,
      fifteen of those directionally-consistent with the original signal. Overall,
      these association findings were robust to analyses that accounted for membership
      of ethnolinguistic subgroups. Overall, the odds ratios for 31 of the 36 SNPs were
      directionally-consistent with those observed in Europeans (p = 3.2*10(-6)).
      Allelic odds ratios and risk allele frequencies in Sri Lankan subjects were not
      systematically different to those reported in Europeans. Genetic risk score and
      risk of T2D were strongly related in Sri Lankans (per allele OR 1.10 [95%CI 1.08
      1.13], p = 1.2*10(-17)). CONCLUSION: Our data indicate that most T2D-risk
      variants identified in Europeans have similar effects in South Asians from Sri
      Lanka, and that systematic difference in common variant associations are unlikely
      to explain inter-ethnic differences in prevalence or presentation of T2D.

PMID- 24926960
TI  - Cu-Ni nanoparticle-decorated graphene based photodetector.
AB  - We report a simple and straight forward approach for the synthesis of Cu-Ni
      graphene hybrid nano-composites. These nano-composites have been characterized
      using AFM, XRD, FTIR spectroscopy and HRTEM. The characterization data clearly
      shows uniform decoration of Cu-Ni nanoparticles on graphene layers. A thin film
      of these nano-composites was found to exhibit unique electrical and photoresponse
      properties, which may be attributed to photothermoelectric and photovoltaic
      effects. The photocurrent measurements indicate superior light absorption and
      long lifetime of this device. 

PMID- 24926959
TI  - Quantification of functionalised gold nanoparticle-targeted knockdown of gene
      expression in HeLa cells.
AB  - INTRODUCTION: Gene therapy continues to grow as an important area of research,
      primarily because of its potential in the treatment of disease. One significant
      area where there is a need for better understanding is in improving the
      efficiency of oligonucleotide delivery to the cell and indeed, following
      delivery, the characterization of the effects on the cell. METHODS: In this
      report, we compare different transfection reagents as delivery vehicles for gold
      nanoparticles functionalized with DNA oligonucleotides, and quantify their
      relative transfection efficiencies. The inhibitory properties of small
      interfering RNA (siRNA), single-stranded RNA (ssRNA) and single-stranded DNA
      (ssDNA) sequences targeted to human metallothionein hMT-IIa are also quantified
      in HeLa cells. Techniques used in this study include fluorescence and confocal
      microscopy, qPCR and Western analysis. FINDINGS: We show that the use of
      transfection reagents does significantly increase nanoparticle transfection
      efficiencies. Furthermore, siRNA, ssRNA and ssDNA sequences all have comparable
      inhibitory properties to ssDNA sequences immobilized onto gold nanoparticles. We
      also show that functionalized gold nanoparticles can co-localize with
      autophagosomes and illustrate other factors that can affect data collection and
      interpretation when performing studies with functionalized nanoparticles.
      CONCLUSIONS: The desired outcome for biological knockdown studies is the
      efficient reduction of a specific target; which we demonstrate by using ssDNA
      inhibitory sequences targeted to human metallothionein IIa gene transcripts that
      result in the knockdown of both the mRNA transcript and the target protein.

PMID- 24926962
TI  - Experimental ruminant models for bovine neosporosis: what is known and what is
      needed.
AB  - At present, bovine neosporosis is an important worldwide concern because of its
      wide geographic distribution and economic impact. Abortion is the main clinical
      sign of bovine neosporosis in both dairy and beef cattle. Ruminant challenge
      models are critical to evaluate potential vaccine candidates to help tackle
      bovine neosporosis and to study pathogenesis and host responses to infection.
      Several research groups have developed ruminant models of Neospora caninum
      infection independently of others, resulting in a high degree of variability due
      to the use of different species of animals, breeds, strains/isolates of N.
      caninum, doses, routes and times of inoculation. Standardization is greatly
      needed to advance research in a more collaborative, timely and efficient manner.
      In the absence of widely accepted international guidelines, this manuscript
      serves to summarize and discuss the different models and parameters currently in
      use. Parameters essential for the development of non-pregnant and pregnant
      ruminant models are outlined and the main knowledge gaps are identified. This
      information could act as the basis to develop a consensus for international
      standard guidelines for ruminant models of neosporosis that would be helpful for
      researchers in this field worldwide.

PMID- 24926961
TI  - PP2A inhibitors suppress migration and growth of PANC-1 pancreatic cancer cells
      through inhibition on the Wnt/beta-catenin pathway by phosphorylation and
      degradation of beta-catenin.
AB  - Cantharidin is an active constituent of mylabris, a traditional Chinese medicine,
      and presents strong anticancer activity in various cell lines. Cantharidin is a
      potent and selective inhibitor of serine/threonine protein phosphatase 2A (PP2A).
      Our previous studies revealed the prospect of application of cantharidin, as well
      as other PP2A inhibitors, in the treatment of pancreatic cancer. However, the
      mechanisms involved in the anticancer effect of PP2A inhibitors have not been
      fully explored. The Wnt/beta-catenin pathway is involved in cell migration and
      proliferation and participates in the progression of pancreatic cancer. If beta
      catenin is phosphorylated and degraded, the Wnt/beta-catenin pathway is blocked.
      PP2A dephosphorylates beta-catenin and keeps the Wnt/beta-catenin pathway active.
      In the present study, we found that PP2A inhibitor treatment induced
      phosphorylation and degradation of beta-catenin. The suppression on the migration
      and growth of PANC-1 pancreatic cancer cells could be attenuated by pretreatment
      with FH535, a beta-catenin pathway inhibitor. Microarray showed that PP2A
      inhibitor treatment induced expression changes in 13 of 138 genes downstream of
      the beta-catenin pathway. Real-time PCR further confirmed that FH535 attenuated
      the expression changes induced by PP2A inhibitors in 6 of these 13 candidate
      genes. These 6 genes, VEGFB, Dkk3, KRT8, NRP1, Cacnalg and WISP2, have been
      confirmed to participate in the migration and/or growth regulation in previous
      studies. Thus, the phosphorylation- and degradation-mediated suppression on beta
      catenin participates in the cytotoxicity of PP2A inhibitors. Our findings may
      provide insight into the treatment of pancreatic cancer using a targeting PP2A
      strategy.

PMID- 24926963
TI  - Two single-nucleotide polymorphisms in the DKK1 gene are associated with
      developmental dysplasia of the hip in the Chinese Han female population.
AB  - AIMS: Developmental dysplasia of the hip (DDH) is a common congenital or acquired
      skeletal disease characterized by subluxation, dislocation, or dysplasia of the
      hip joint. This study aimed to explore the potential impact of Dickkopf-1 (DKK1)
      gene polymorphisms on embryonic hip joint development and the course of DDH.
      METHODS: One hundred ninety-two unrelated Chinese Han female DDH patients and 191
      unrelated, healthy, ethnically matched female controls were recruited and
      genotyped for two tag single-nucleotide polymorphisms (SNPs) of DKK1 using the
      Sequenom method. RESULTS: One of the two DKK1 tag SNPs, rs11001560, was not shown
      to be significantly statistically different in allele frequency between DDH
      patients and control groups (chi(2)=0.898, df=1, p=0.343). However, a significant
      difference in genotype distribution was observed (chi(2)=21.987, df=2, p<0.0001).
      For SNP rs1569198, significant differences were observed in both allele frequency
      and genotype distribution between the DDH group and control group (chi(2)=31.484,
      df=1, p<0.0001 and chi(2)=30.323, df=2, p<0.0001). The A allele frequency of
      rs1569198 has a significant association to increased risk of DDH development
      (odds ratio [OR]=3.032, 95% confidence interval [95% CI]: 2.034-4.519).
      CONCLUSION: In conclusion, the association between two tag SNPs of the DKK1 gene
      and DDH development reached statistical significance in our study population; the
      results of our genetic association analysis indicated that DKK1 may be a good
      candidate responsible for DDH development in the Chinese Han female population.

PMID- 24926964
TI  - A rare example of nickel(ii) chains based on a heteroscorpionate-like ligand with
      quadruple imidazolyl interactions.
AB  - The first nickel(ii) complex with the heteroscorpionate-like bridging ligand
      DIMMAL (2-di1H-2-imidazolylmethylmalonate), [Ni(DIMMAL)(H2O)3]n.3nH2O (1), is a
      one-dimensional coordination polymer whose structure shows regular Ni(ii) chains
      with H-bonding inter-chain interactions and a rare example of a Quadruple
      Imidazolyl Embrace (QIE). The Ni(ii) chain shows a weak antiferromagnetic
      interaction that can be modelled with a regular S = 1 chain model including a
      zero field splitting with g = 2.270, J = -1.5 cm(-1) and D = -2.26 cm(-1). 

PMID- 24926965
TI  - Recent advances in zinc-air batteries.
AB  - Zinc-air is a century-old battery technology but has attracted revived interest
      recently. With larger storage capacity at a fraction of the cost compared to
      lithium-ion, zinc-air batteries clearly represent one of the most viable future
      options to powering electric vehicles. However, some technical problems
      associated with them have yet to be resolved. In this review, we present the
      fundamentals, challenges and latest exciting advances related to zinc-air
      research. Detailed discussion will be organized around the individual components
      of the system - from zinc electrodes, electrolytes, and separators to air
      electrodes and oxygen electrocatalysts in sequential order for both primary and
      electrically/mechanically rechargeable types. The detrimental effect of CO2 on
      battery performance is also emphasized, and possible solutions summarized.
      Finally, other metal-air batteries are briefly overviewed and compared in favor
      of zinc-air. 

PMID- 24926966
TI  - Solidification of a colloidal hard sphere like model system approaching and
      crossing the glass transition.
AB  - We investigated the process of vitrification and crystallization in a model
      system of colloidal hard spheres. The kinetics of the solidification process was
      measured using time resolved static light scattering, while the time evolution of
      the dynamic properties was determined using time resolved dynamic light
      scattering. By performing further analysis we confirm that solidification of hard
      sphere colloids is mediated by precursors. Analyzing the dynamic properties we
      can show that the long time dynamics and thus the shear rigidity of the
      metastable melt is highly correlated with the number density of solid clusters
      (precursors) nucleated. In crystallization these objects convert into highly
      ordered crystals whereas in the case of vitrification this conversion is blocked
      and the system is (temporarily) locked in the metastable precursor state. From
      the early stages of solidification one cannot clearly conclude whether the melt
      will crystallize or vitrify. Furthermore our data suggests that colloidal hard
      sphere glasses can crystallize via homogeneous nucleation. 

PMID- 24926967
TI  - Electrochemistry provides a point-of-care approach for the marker indicative of
      Pseudomonas aeruginosa infection of cystic fibrosis patients.
AB  - It has recently been demonstrated that 2-aminoacetophenone (2-AA) is a chemical
      indicator in exhaled air/breath of Pseudomonas aeruginosa infection associated
      with progressive life threatening decline of lung function in cystic fibrosis
      sufferers [Scott-Thomas et al., BMC Pulm. Med., 2010, 10, 56]. Currently the
      detection of 2-AA involves laboratory based instrumentation such as mass
      spectrometry and a hand-held point-of-care type breath device would be ideal in
      providing real-time results within seconds to accelerate patient care decision
      making processes. To this end, we demonstrate proof-of-concept that the chemical
      marker 2-AA, indicative of Pseudomonas aeruginosa infection, can be measured
      using electrochemical based sensing strategies. A range of commercially available
      electrode substrates are explored demonstrating for the first time that 2-AA is
      electrochemically active within aqueous based solutions providing an
      (electro)analytical signal. Glassy carbon, boron-doped diamond and platinum
      electrodes have been explored towards the electrochemical oxidation of 2-AA.
      Electrode fouling is observed requiring pre-treatment in the form of mechanical
      polishing between voltammetric scans and measurements. To alleviate this, screen
      printed graphite electrodes are shown to be a more viable option for
      implementation into breath sensing devices and overcome the fouling problem since
      due to their low cost and disposable nature, a new electrode can be used for each
      measurement. The analytical utility of the platinum, screen-printed and boron
      doped diamond electrodes were found to correspond to 6.85, 7.66 and 4.86 mM
      respectively. The challenges associated with the electrochemical sensing of 2-AA
      in breath that need to be overcome are discussed. This generic approach where
      electrochemical based technology is used to provide measurements for chemical
      markers in exhaled air/breath for medical diagnostics termed electrochemical
      breathprints (ec-breathprints), has the potential to be developed into a hand
      held point-of-care breath diagnostic tool for identifying Pseudomonas aeruginosa
      infection in exhaled air/breath. 

PMID- 24926968
TI  - Structurational divergence theory as explanation for troublesome outcomes in
      nursing communication.
AB  - Structurational divergence (SD) theory captures negative communication cycles
      resulting from interpenetration of incompatible meaning structures. It is
      estimated that 12-15% of practicing nurses suffer from a problematic level of SD.
      With a sample of 713 nurses (57 departments) in a large hospital, this study
      tests a model positing SD as a root explanation of nursing job satisfaction and
      turnover. A number of variables long presumed to be explanations for job
      satisfaction and turnover were hypothesized as mediators between SD and those
      outcomes. Path analysis showed support for burnout, role conflict, bullying, and
      organizational identification as useful mediators, explaining 68% of the variance
      in job satisfaction, and 45% in intentions to leave. The study also explores
      relationships between SD and hospital quality indicators. SD is a concern because
      it powerfully explains a number of poor outcomes and provides an underlying
      explanation for a number of factors that predict job satisfaction and turnover. 

PMID- 24926969
TI  - Acalvaria.
AB  - Acalvaria is a rare congenital malformation characterized by an absence of skin
      and skull. The authors describe a newborn at an estimated 38 weeks gestational
      age who was delivered via cesarean section from a 32-year-old mother. Upon
      delivery, the child was noted to have a frontal encephalocele and an absence of
      calvaria including skull and skin overlying the brain. A thin membrane
      representing dura mater was overlying the cortical tissue. After multiple
      craniofacial operations, including repair of the encephalocele and application of
      cultured keratinocytes over the rostral defect, the patient demonstrated
      significant closure of the calvarial defect and was alive at an age of more than
      17 months with near-average development. 

PMID- 24926970
TI  - The pathological spectrum of solid CNS metastases in the pediatric population.
AB  - OBJECT: Collectively, metastatic tumors are the most common malignancy
      encountered in the adult central nervous system (CNS), arising most often from
      lung, breast, skin, and gastrointestinal tract carcinomas. Limited information is
      available in the literature regarding solid nonhematopoietic CNS metastases in
      children. The authors carried out a retrospective study of pediatric metastatic
      neoplasms to the CNS treated in a 30-year period to characterize their frequency,
      common histological subtypes, and sites of origin. METHODS: The archival
      pathology files were searched (1981-2011) for metastatic tumors to the CNS in
      patients 21 years of age and younger. Pathology material was reviewed, tumors
      were classified by site of origin and histological subtype, and survival was
      evaluated. RESULTS: The authors identified 26 patients with solid
      nonhematopoietic CNS metastases out of 1135 pediatric CNS tumors diagnosed from
      1981 to 2011. Patients ranged in age from 1.5 to 20.3 years and were equally
      divided between sexes. Most CNS metastases were supratentorial (85%) and solitary
      (65%). The mean interval from primary malignant diagnosis to CNS metastasis was
      27 months. Sites of origin included kidney/adrenal, bone/soft tissue, gonads,
      head and neck, lung, and liver. Mean survival after CNS involvement was 36.6
      months. Overall 1-year and 5-year survival rates were 52% and 16%, respectively.
      CONCLUSIONS: In neuropathology practice, nonhematopoietic pediatric CNS
      metastases are far less common than are nonhematopoietic adult CNS metastases,
      accounting for approximately 2% of all pediatric CNS tumors. The most common
      tumors to exhibit CNS metastasis are of kidney/adrenal origin, followed by those
      from bone/soft tissue. As expected, prognosis is dismal, despite aggressive
      therapy.

PMID- 24926971
TI  - Factors associated with ventricular catheter movement and inaccurate catheter
      location: post hoc analysis of the hydrocephalus clinical research network
      ultrasound-guided shunt placement study.
AB  - OBJECT: Shunt survival may improve when ventricular catheters are placed into the
      frontal horn or trigone of the lateral ventricle. However, techniques for
      accurate catheter placement have not been developed. The authors recently
      reported a prospective study designed to test the accuracy of catheter placement
      with the assistance of intraoperative ultrasound, but the results were poor
      (accurate placement in 59%). A major reason for the poor accurate placement rate
      was catheter movement that occurred between the time of the intraoperative
      ultrasound image and the first postoperative scan (33% of cases). The control
      group of non-ultrasound using surgeons also had a low rate of accurate placement
      (accurate placement in 49%). The authors conducted an exploratory post hoc
      analysis of patients in their ultrasound study to identify factors associated
      with either catheter movement or poor catheter placement so that improved
      surgical techniques for catheter insertion could be developed. METHODS: The
      authors investigated the following risk factors for catheter movement and poor
      catheter placement: age, ventricular size, cortical mantle thickness, surgeon
      experience, surgeon experience with ultrasound prior to trial, shunt entry site,
      shunt hardware at entry site, ventricular catheter length, and use of an
      ultrasound probe guide for catheter insertion. Univariate analysis followed by
      multivariate logistic regression models were used to determine which factors were
      independent risk factors for either catheter movement or inaccurate catheter
      location. RESULTS: In the univariate analyses, only age < 6 months was associated
      with catheter movement (p = 0.021); cortical mantle thickness < 1 cm was near
      significant (p = 0.066). In a multivariate model, age remained significant after
      adjusting for cortical mantle thickness (OR 8.35, exact 95% CI 1.20-infinity).
      Univariate analyses of factors associated with inaccurate catheter placement
      showed that age < 6 months (p = 0.001) and a posterior shunt entry site (p =
      0.021) were both associated with poor catheter placement. In a multivariate
      model, both age < 6 months and a posterior shunt entry site were independent risk
      factors for poor catheter placement (OR 4.54, 95% CI 1.80-11.42, and OR 2.59, 95%
      CI 1.14-5.89, respectively). CONCLUSIONS: Catheter movement and inaccurate
      catheter placement are both more likely to occur in young patients (< 6 months).
      Inaccurate catheter placement is also more likely to occur in cases involving a
      posterior shunt entry site than those involving an anterior shunt entry site.
      Future clinical studies aimed at improving shunt placement techniques must
      consider the effects of young age and choice of entry site on catheter location.

PMID- 24926972
TI  - Thirty-day outcomes of cerebrospinal fluid shunt surgery: data from the National
      Surgical Quality Improvement Program-Pediatrics.
AB  - OBJECT: Cerebrospinal fluid shunts are the mainstay of the treatment of
      hydrocephalus. In past studies, outcomes of shunt surgery have been analyzed
      based on follow-up of 1 year or longer. The goal of the current study is to
      characterize 30-day shunt outcomes, to identify clinical risk factors for shunt
      infection and failure, and to develop statistical models that might be used for
      risk stratification. METHODS: Data for 2012 were obtained from the National
      Surgical Quality Improvement Program-Pediatrics (NSQIP-P) of the American College
      of Surgeons. Files with index surgical procedures for insertion or revision of a
      CSF shunt composed the study set. Returns to the operating room within 30 days
      for shunt infection and for shunt failure without infection were the study end
      points. Associations with a large number of potential clinical risk factors were
      analyzed on a univariate basis. Logistic regression was used for multivariate
      analysis. RESULTS: There were 1790 index surgical procedures analyzed. The
      overall rates of shunt infection and shunt failure without infection were 2.0%
      and 11.5%, respectively. Male sex, steroid use in the preceding 30 days, and
      nutritional support at the time of surgery were risk factors for shunt infection.
      Cardiac disease was a risk factor for shunt failure without infection, and
      initial shunt insertion, admission during the second quarter, and neuromuscular
      disease appeared to be protective. There was a weak association of increasing age
      with shunt failure without infection. Models based on these factors accounted for
      no more than 6% of observed variance. Construction of stable statistical models
      with internal validity for risk adjustment proved impossible. CONCLUSIONS: The
      precision of the NSQIP-P dataset has allowed identification of risk factors for
      shunt infection and for shunt failure without infection that have not been
      documented previously. Thirty-day shunt outcomes may be useful quality metrics,
      possibly even without risk adjustment. Whether important variation in 30-day
      outcomes exists among institutions or among neurosurgeons is yet unknown.

PMID- 24926975
TI  - Editorial.

PMID- 24926973
TI  - Socioeconomic patterning in the incidence and survival of children and young
      people diagnosed with malignant melanoma in northern England.
AB  - Previous studies have found marked increases in melanoma incidence. The increase
      among young people in northern England was especially apparent among females.
      However, overall 5-year survival has greatly improved. The present study aimed to
      determine whether socioeconomic factors may be involved in both etiology and
      survival. All 224 cases of malignant melanoma diagnosed in patients aged 10-24
      years during 1968-2003 were extracted from a specialist population-based regional
      registry. Negative binomial regression was used to examine the relationship
      between incidence and area-based measures of socioeconomic deprivation and small
      area population density. Cox regression was used to analyze the relationship
      between survival and deprivation and population density. There was significantly
      decreased risk associated with living in areas of higher unemployment (relative
      risk per 1% increase in unemployment=0.93; 95% confidence interval (CI) 0.90
      0.96, P<0.001). Survival was better in less deprived areas (hazard ratio (HR) per
      tertile of household overcrowding=1.52; 95% CI 1.05-2.20; P=0.026), but this
      effect was reduced in the period 1986-2003 (HR=0.61; 95% CI 0.40-0.92; P=0.018).
      This study found that increased risk of melanoma was linked with some aspects of
      greater affluence. In contrast, worse survival was associated with living in a
      more deprived area. 

PMID- 24926976
TI  - Serotonin and gender-specific psychiatric disorders.
AB  - The serotonergic system has been linked to the etiology of several, albeit
      disparate, psychiatric disorders. The accumulation of many lines of evidence
      support the view that there are gender differences in the serotonergic system in
      humans. It is further proposed that a gender differentiated serotonergic system
      acts as the nidus for the development of gender-specific psychiatric disorders.
      Depression, anxiety and eating disorders are largely seen in females, whereas
      alcoholism, aggressivity and suicide predominate in males. Evidence from both
      animal and human studies suggesting that the serotonergic system mediates between
      social-environmental experience and biological states is presented and reviewed.
      A reconceptualization of the serotonergic system as a gender-specific
      psychobiological interface is proposed. (Int J Psych Clin Prac 1997; 1: 3-13). 

PMID- 24926977
TI  - Muscarinic therapies in Alzheimer's disease; from palliative treatments to
      disease modification.
AB  - Cholinergic therapies for Alzheimer's disease (AD) have been developed following
      painstaking neuropathological and neurochemical studies. Drugs based upon this
      approach are in development and it is hoped that these compounds will be of some
      use as palliative therapy. However, increasing evidence from molecular biology
      suggests that increasing cholinergic neurotransmission might not only alter
      cognition but also modify disease progression. The evidence that muscarinic
      induced increases in protein kinase C activity favourably alter amyloid precursor
      protein metabolism and tau phosphorylation is reviewed. A unifying hypothesis of
      AD pathogenesis brings together plaque and tangle formation, suggesting that
      cholinergic therapies in development may have far-reaching implications as
      treatments for AD. (Int J Psych Clin Pract 1997; 1: 15-20). 

PMID- 24926978
TI  - New aspects of diagnosis and pharmacotherapy of eating disorders.
AB  - This paper points out recent diagnostic features of bulimia and anorexia nervosa
      and of the recently defined 'binge eating disorder'. The pharmacologic treatment
      approaches for these conditions will be reviewed by discussing the results of
      randomized controlled studies. For anorexia nervosa (AN), the outcome of
      pharmacotherapy has been poor, in contrast to bulimia nervosa (BN) and binge
      eating disorder (BED), where pharmacological treatment, primarily with
      antidepressants, has proved to be effective, at least in the short run. However,
      long-term outcome studies are still awaited. (MJ Psych Clin Pract 1997; 1: 21
      35). 

PMID- 24926979
TI  - Chewing and spitting out food in eating disorder.
AB  - The case of a 19-year-old woman with an eating disorder is presented, whose prime
      symptom was chewing and spitting out food. She intentionally chose this behaviour
      as the best strategy to avoid gaining weight while enjoying the taste of large
      quantities of food. (IntJ Psych Clin Pract 1997; 1: 37-38). 

PMID- 24926980
TI  - Prevention of depression and suicide by education and medication: impact on male
      suicidality. An update from the Gotland study.
AB  - Depression is an endemic disease with high morbidity, and a high mortality in
      depression-related suicide. Suicidal tendencies, especially among males, are
      increasing today in East European countries. General practitioners are considered
      to have a very important role in the prevention and treatment of depression.
      Matters of depression are more openly discussed in society. Patients showing up
      in primary care are nowadays less reluctant to see depression as a causative
      factor behind their symptoms. Taboos concerning the stigma of depression and
      suicidality are weaker. In spite of this, important problems still exist
      regarding poor diagnostic and treatment routines in primary care and the
      inability of depressive and suicidal men to seek for help or to be recognized. In
      the years 1983-1984, the Swedish Committee for Prevention and Treatment of
      Depression (PTD) offered an educational programme to all general practitioners
      (GPs) on the Swedish island of Gotland. During the 1980s this education was shown
      to lead to a significant decrease in inpatient care, morbidity, suicide,
      mortality and costs of depressive illness on the island. The use of anxiolytic
      and sedative medication decreased and that of antidepressant medication
      increased. This all showed that an educational programme in primary care on
      depression and suicide was effective. However, the effects faded and,
      unexpectedly, the number of male suicides was almost unaffected by the
      educational programme and by the GPs' ability to diagnose and treat depression.
      Repeated educational activities during the 1990s again led to a decrease in
      suicides, mainly in females. Also, the increase in antidepressant prescriptions
      following GP education in the 1990s was mostly in the treatment of female
      patients. One of the reasons was that few suicidal males are known to the medical
      services although many of these people are known to the police and social welfare
      services. The reasons why depressed and suicidal men do not show up in the
      medical services are discussed, and found to lie in the differences between the
      male and the female depressive syndrome, leading to difficulties in reaching,
      diagnosing and treating these patients. Strategies for finding and treating
      suicidal depressives are discussed. One conclusion is that males are as often
      depressed as females, but in different ways, and that one of the reasons behind
      the dramatic over-representation of males amongst suicide victims may be found in
      the low rate of diagnosis and treatment of the male depressive syndrome, (hit J
      Psych Clin Pract 1997; 1: 39-46). 

PMID- 24926981
TI  - Effects of antidepressant drugs on sexual function.
AB  - Adequate sexual expression is an essential part of human relationships, enhancing
      quality of life and providing a sense of physical, psychological and social well
      being. Unfortunately, depression is associated with impairments of sexual
      function and satisfaction. These problems can worsen a quality of life that is
      already reduced by the effects of depressive illness. The existing antidepressant
      drugs are far from ideal, most having adverse effects on sexual function.
      Unfortunately, the exact incidence of sexual dysfunction during treatment with
      many antidepressants is not known. Disturbances of sexual interest and
      performance will only be detected in a reliable fashion when systematic enquiries
      are made during the course of the standard clinical interview. Growing awareness
      of the adverse effects of many antidepressants on sexual function has led to some
      re-evaluation of the earlier claims for the good tolerability of many of the
      newer drugs. There is a clear need for further well-designed controlled studies
      of the effects of antidepressants on sexual function, so that this aspect of the
      tolerability of differing drugs can be assessed more reliably. (IntJ Psych Clin
      Pract 1997; 1: 47-58). 

PMID- 24926982
TI  - The value of selective serotonin re-uptake inhibitors (SSRIs) in the treatment of
      panic disorder with and without agoraphobia.
AB  - Many promising medical and psychotherapeutic treatment approaches have been
      developed for panic disorder with or without agoraphobia in recent years.
      Previously, good results have been seen with the TCAs (imipramine, clomipramine)
      and alprazolam. This review represents a comprehensive survey of all existing
      studies of the efficacy of the selective serotonin re-uptake inhibitors (SSRIs)
      paroxetine and fluvoxamine. There is conclusive evidence that the effectiveness
      of these drugs-paroxetine in particular-can be regarded as proven. Moreover,
      there are indications that a quicker response and better tolerability can be
      achieved than with TCA. A phased therapy model demonstrates how SSRIs can amplify
      and therefore improve the treatment of panic disorder. Reference is also made to
      differential indications with regard to the severity and the duration of the
      disorder. (Int J Psych Clin Pract 1997; 1: 59-67). 

PMID- 24926983
TI  - National Confidential Inquiry into Suicide and Homicide by People with Mental
      Illness: recent developments.
AB  - The National Confidential Inquiry into Suicide and Homicide by People with Mental
      Illness, originally established in 1992, was relocated to Manchester in 1996 with
      the aim of studying homicides and suicides by people with mental illness in the
      UK. The Inquiry collects a comprehensive national sample of homicides and
      suicides, using data from the Home Office and court reports in the case of
      homicide, and from public health mortality files for suicide. When there has been
      contact with specialist mental health services, mental health teams are asked to
      provide further information in a standard questionnaire. The Inquiry is
      particularly interested in final contact with services prior to death and
      collects detailed information on various priority groups and the process of risk
      assessment. The findings will be the basis of recommendations on to clinical
      practice and training, with the aim of reducing avoidable deaths resulting from
      mental illness (Int J Psych Clin Pract 1997; 1: 69-71). 

PMID- 24926984
TI  - Psychiatric aspects of irritable bowel syndrome.
AB  - The considerable psychiatric comorbidity in patients with irritable bowel
      syndrome (IBS) is noted and the concept of depressive spectrum disorder is
      briefly discussed. The results of a recently published study examining the effect
      of psychiatric comorbidity on the outcome of IBS are presented and discussed.
      Finally, details of a double-blind, placebo-controlled trial of Nefazodone in the
      treatment of patients with IBS, which has recently begun in South Wales, are
      discussed. (Int J Psych Clin Pract 1997; 1: 73-74). 

PMID- 24926985
TI  - Capsaicin-induced activation of p53-SMAR1 auto-regulatory loop down-regulates
      VEGF in non-small cell lung cancer to restrain angiogenesis.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Despite
      decades of research, the treatment options for lung cancer patients remain
      inadequate, either to offer a cure or even a substantial survival advantage owing
      to its intrinsic resistance to chemotherapy. Our results propose the
      effectiveness of capsaicin in down-regulating VEGF expression in non-small cell
      lung carcinoma (NSCLC) cells in hypoxic environment. Capsaicin-treatment re
      activated p53-SMAR1 positive feed-back loop in these cells to persuade p53
      mediated HIF-1alpha degradation and SMAR1-induced repression of Cox-2 expression
      that restrained HIF-1alpha nuclear localization. Such signal-modulations
      consequently down regulated VEGF expression to thwart endothelial cell migration
      and network formation, pre-requisites of angiogenesis in tumor micro-environment.
      The above results advocate the candidature of capsaicin in exclusively targeting
      angiogenesis by down-regulating VEGF in tumor cells to achieve more efficient and
      cogent therapy of resistant NSCLC. 

PMID- 24926987
TI  - Risky business.

PMID- 24926986
TI  - Correlation of intra-tumor 18F-FDG uptake heterogeneity indices with perfusion CT
      derived parameters in colorectal cancer.
AB  - METHODS: Thirty patients with proven colorectal cancer prospectively underwent
      integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT
      blood flow parametric maps and PET images were analyzed. Correlations between PET
      heterogeneity and perfusion CT were assessed by Spearman's rank correlation
      analysis. RESULTS: Blood flow visualization provided by DCE-CT images was
      significantly correlated with 18F-FDG PET metabolically active tumor volume as
      well as with uptake heterogeneity for patients with stage III/IV tumors
      (|rho|:0.66 to 0.78; p-value<0.02). CONCLUSION: The positive correlation found
      with tumor blood flow indicates that intra-tumor heterogeneity of 18F-FDG PET
      accumulation reflects to some extent tracer distribution and consequently
      indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with
      physiological processes such as tumor vascularization.

PMID- 24926988
TI  - Re: Lange R, Hoerer J, Schreiber C. What are the obstacles to training in surgery
      for congenital heart disease in Germany? Thorac Cardiovasc Surg 2013; 61: 273
      277.

PMID- 24926989
TI  - Potentiostatic reversible photoelectrochromism: an effect appearing in nanoporous
      TiO2/Ni(OH)2 thin films.
AB  - In the field of energy saving, finding composite materials with the ability of
      coloring upon both illumination and change of the applied electrode potential
      keeps on being an important goal. In this context, chemical bath deposition of
      Ni(OH)2 into nanoporous TiO2 thin films supported on conducting glass leads to
      electrodes showing both conventional electrochromic behavior (from colorless to
      dark brown and vice versa) together with photochromism at constant applied
      potential. The latter phenomenon, reported here for the first time, is
      characterized by fast and reversible coloration upon UV illumination. The
      bleaching kinetics shows first order behavior with respect to the Ni(III) centers
      in the film, and an order 1.2 with respect to electrons in the TiO2 film. From a
      more applied point of view, this study opens up the possibility of having two
      mode smart windows showing not only conventional electrochromism but also
      reversible darkening upon illumination. 

PMID- 24926990
TI  - Dislocated double-layer metal gratings: an efficient unidirectional coupler.
AB  - We propose theoretically and demonstrate experimentally a dislocated double-layer
      metal grating structure, which operates as a unidirectional coupler capable of
      launching surface plasmon polaritons in a desired direction under normal
      illumination. The structure consists of a slanted dielectric grating sandwiched
      between two gold gratings. The upper gold grating has a nonzero lateral relative
      displacement with respect to the lower one. Numerical simulations show that a
      grating structure with 7 periods can convert 49% of normally incident light into
      surface plasmons with a contrast ratio of 78 between the powers of the surface
      plasmons launched in two opposite directions. We explain the unidirectional
      coupling phenomenon by the dislocation-induced interference of the diffracted
      waves from the upper and lower gold gratings. Furthermore, we developed a simple
      and cost-effective technique to fabricate the structure via tilted two-beam
      interference lithography and subsequent shadow deposition of gold. The
      experimental results demonstrate a coupling efficiency of 36% and a contrast
      ratio of 43. The relatively simple periodic nature of our structure lends itself
      to large-scale low-cost fabrication and simple theoretical analysis. Also, unlike
      the previous unidirectional couplers based on aperiodic structures, the design
      parameters of our unidirectional coupler can be determined analytically.
      Therefore, this structure can be an important component for surface-plasmon-based
      nanophotonic circuits by providing an efficient interface between free-space and
      surface plasmon waves. 

PMID- 24926991
TI  - Targeting the NF-E2-related factor 2 pathway: a novel strategy for glioblastoma
      (review).
AB  - Glioblastoma is the most common and malignant subtype among all brain tumors.
      Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential component of
      cellular defense against a variety of endogenous and exogenous stresses. A marked
      increase in research over the past few decades focusing on Nrf2 and its role in
      regulating glioblastoma has revealed the potential value of Nrf2 in the treatment
      of glioblastoma. In the present review, we discuss a novel framework of Nrf2 in
      the regulation of glioblastoma and the mechanisms regarding the downregulation of
      Nrf2 in treating glioblastoma. The candidate mechanisms include direct and
      indirect means. Direct mechanisms target tumor molecular pathways in order to
      overcome resistance to chemotherapy and radiotherapy, to inhibit proliferation,
      to block invasion and migration, to induce apoptosis, to promote differentiation,
      to enhance autophagy and to target glioblastoma stem cells. Indirect mechanisms
      target the reaction between glioblastoma cells and the surrounding
      microenvironment. Overall, the value of the Nrf2 pathway in glioblastoma provides
      a promising opportunity for new approaches by which to treat glioblastoma.

PMID- 24926992
TI  - Light-dependent control of redox balance and auxin biosynthesis in plants.
AB  - Auxin, indole-3-acetic acid (IAA), plays a crucial role for morphogenesis,
      development, growth, and tropisms in many plant species. Auxin biosynthesis is
      accomplished via specific pathways depending on several enzymes starting from
      amino acid, tryptophan. Auxin biosynthesis in maize is particularly active at the
      tip of coleoptile expressing abundant YUCCA (YUC) protein, which is essential for
      auxin biosynthesis. In vitro experiment demonstrated that precursor of auxin
      molecule; indole-3-acetaldehyde (IAAld) was generated by illumination of the
      mixture of tryptophan and flavin in non-enzymatic manner. In addition, we have
      detected immediate production of reactive oxygen species (ROS) in illuminated
      Arabidopsis root cells. In this perspective, we are proposing the non-enzymatic
      regulation of redox homeostasis and auxin biosynthesis throughout the plant body
      under variable environmental light conditions.

PMID- 24926993
TI  - Assessing the accuracy and feasibility of a refractive error screening program
      conducted by school teachers in pre-primary and primary schools in Thailand.
AB  - INTRODUCTION: As part of the development of a system for the screening of
      refractive error in Thai children, this study describes the accuracy and
      feasibility of establishing a program conducted by teachers. OBJECTIVE: To assess
      the accuracy and feasibility of screening by teachers. METHODS: A cross-sectional
      descriptive and analytical study was conducted in 17 schools in four provinces
      representing four geographic regions in Thailand. A two-staged cluster sampling
      was employed to compare the detection rate of refractive error among eligible
      students between trained teachers and health professionals. Serial focus group
      discussions were held for teachers and parents in order to understand their
      attitude towards refractive error screening at schools and the potential success
      factors and barriers. RESULTS: The detection rate of refractive error screening
      by teachers among pre-primary school children is relatively low (21%) for mild
      visual impairment but higher for moderate visual impairment (44%). The detection
      rate for primary school children is high for both levels of visual impairment
      (52% for mild and 74% for moderate). The focus group discussions reveal that both
      teachers and parents would benefit from further education regarding refractive
      errors and that the vast majority of teachers are willing to conduct a school
      based screening program. CONCLUSION: Refractive error screening by health
      professionals in pre-primary and primary school children is not currently
      implemented in Thailand due to resource limitations. However, evidence suggests
      that a refractive error screening program conducted in schools by teachers in the
      country is reasonable and feasible because the detection and treatment of
      refractive error in very young generations is important and the screening program
      can be implemented and conducted with relatively low costs.

PMID- 24926994
TI  - Inhibition of exotoxin production by mobile genetic element SCCmec-encoded psm
      mec RNA is conserved in staphylococcal species.
AB  - Staphylococcal species acquire antibiotic resistance by incorporating the mobile
      genetic element SCCmec. We previously found that SCCmec-encoded psm-mec RNA
      suppresses exotoxin production as a regulatory RNA, and the psm-mec translation
      product increases biofilm formation in Staphylococcus aureus. Here, we examined
      whether the regulatory role of psm-mec on host bacterial virulence properties is
      conserved among other staphylococcal species, S. epidermidis and S. haemolyticus,
      both of which are important causes of nosocomial infections. In S. epidermidis,
      introduction of psm-mec decreased the production of cytolytic toxins called
      phenol-soluble modulins (PSMs) and increased biofilm formation. Introduction of
      psm-mec with a stop-codon mutation that did not express PSM-mec protein but did
      express psm-mec RNA also decreased PSM production, but did not increase biofilm
      formation. Thus, the psm-mec RNA inhibits PSM production, whereas the PSM-mec
      protein increases biofilm formation in S. epidermidis. In S. haemolyticus,
      introduction of psm-mec decreased PSM production, but did not affect biofilm
      formation. The mutated psm-mec with a stop-codon also caused the same effect.
      Thus, the psm-mec RNA also inhibits PSM production in S. haemolyticus. These
      findings suggest that the inhibitory role of psm-mec RNA on exotoxin production
      is conserved among staphylococcal species, although the stimulating effect of the
      psm-mec gene on biofilm formation is not conserved. 

PMID- 24926995
TI  - Allele-specific silencing of mutant huntingtin in rodent brain and human stem
      cells.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      resulting from polyglutamine expansion in the huntingtin (HTT) protein and for
      which there is no cure. Although suppression of both wild type and mutant HTT
      expression by RNA interference is a promising therapeutic strategy, a selective
      silencing of mutant HTT represents the safest approach preserving WT HTT
      expression and functions. We developed small hairpin RNAs (shRNAs) targeting
      single nucleotide polymorphisms (SNP) present in the HTT gene to selectively
      target the disease HTT isoform. Most of these shRNAs silenced, efficiently and
      selectively, mutant HTT in vitro. Lentiviral-mediated infection with the shRNAs
      led to selective degradation of mutant HTT mRNA and prevented the apparition of
      neuropathology in HD rat's striatum expressing mutant HTT containing the various
      SNPs. In transgenic BACHD mice, the mutant HTT allele was also silenced by this
      approach, further demonstrating the potential for allele-specific silencing.
      Finally, the allele-specific silencing of mutant HTT in human embryonic stem
      cells was accompanied by functional recovery of the vesicular transport of BDNF
      along microtubules. These findings provide evidence of the therapeutic potential
      of allele-specific RNA interference for HD. 

PMID- 24926996
TI  - Evolution of enzymatic activities in the enolase superfamily: galactarate
      dehydratase III from Agrobacterium tumefaciens C58.
AB  - The genome of Agrobacterium tumefaciens C58 encodes 12 members of the enolase
      superfamily (ENS), eight of which are members of the mandelate racemase (MR)
      subgroup and, therefore, likely to be acid sugar dehydratases. Using a library of
      77 acid sugars for high-throughput screening, one protein (UniProt entry A9CG74;
      locus tag Atu4196) showed activity with both m-galactarate and d-galacturonate.
      Two families of galactarate dehydratases had been discovered previously in the
      ENS, GalrD/TalrD [Yew, W. S., et al. (2007) Biochemistry 46, 9564-9577] and GalrD
      II [Rakus, J. F., et al. (2009) Biochemistry 48, 11546-11558]; these have
      different active site acid/base catalysis and have no activity with d
      galacturonate. A9CG74 dehydrates m-galactarate to form 2-keto-3-deoxy-galactarate
      but does not dehydrate d-galacturonate as expected. Instead, when A9CG74 is
      incubated with d-galacturonate, 3-deoxy-d-xylo-hexarate or 3-deoxy-d-lyxo
      hexarate is formed. In this reaction, instead of abstracting the C5 proton alpha
      to the carboxylate group, the expected reaction for a member of the ENS, the
      enzyme apparently abstracts the proton alpha to the aldehyde group to form 3
      deoxy-d-threo-hexulosuronate that undergoes a 1,2-hydride shift similar to the
      benzylic acid rearrangement to form the observed product. A. tumefaciens C58 does
      not utilize m-galactarate as a carbon source under the conditions tested in this
      study, although it does utilize d-galacturonate, which is a likely precursor to m
      galactarate. The gene encoding A9CG74 and several genome proximal genes were
      upregulated with d-galacturonate as the carbon source. One of these, a member of
      the dihydrodipicolinate synthase superfamily, catalyzes the dehydration and
      subsequent decarboxylation of 2-keto-3-deoxy-d-galactarate to alpha-ketoglutarate
      semialdehyde, thereby providing a pathway for the conversion of m-galactarate to
      alpha-ketoglutarate semialdehyde. 

PMID- 24926997
TI  - Expansion of the preimmune antibody repertoire by junctional diversity in Bos
      taurus.
AB  - Cattle have a limited range of immunoglobulin genes which are further diversified
      by antigen independent somatic hypermutation in fetuses. Junctional diversity
      generated during somatic recombination contributes to antibody diversity but its
      relative significance has not been comprehensively studied. We have investigated
      the importance of terminal deoxynucleotidyl transferase (TdT) -mediated
      junctional diversity to the bovine immunoglobulin repertoire. We also searched
      for new bovine heavy chain diversity (IGHD) genes as the information of the
      germline sequences is essential to define the junctional boundaries between gene
      segments. New heavy chain variable genes (IGHV) were explored to address the gene
      usage in the fetal recombinations. Our bioinformatics search revealed five new
      IGHD genes, which included the longest IGHD reported so far, 154 bp. By genomic
      sequencing we found 26 new IGHV sequences that represent potentially new IGHV
      genes or allelic variants. Sequence analysis of immunoglobulin heavy chain cDNA
      libraries of fetal bone marrow, ileum and spleen showed 0 to 36 nontemplated N
      nucleotide additions between variable, diversity and joining genes. A maximum of
      8 N nucleotides were also identified in the light chains. The junctional base
      profile was biased towards A and T nucleotide additions (64% in heavy chain VD,
      52% in heavy chain DJ and 61% in light chain VJ junctions) in contrast to the
      high G/C content which is usually observed in mice. Sequence analysis also
      revealed extensive exonuclease activity, providing additional diversity. B
      lymphocyte specific TdT expression was detected in bovine fetal bone marrow by
      reverse transcription-qPCR and immunofluorescence. These results suggest that TdT
      mediated junctional diversity and exonuclease activity contribute significantly
      to the size of the cattle preimmune antibody repertoire already in the fetal
      period. 

PMID- 24926998
TI  - Insights from computational modeling in inflammation and acute rejection in limb
      transplantation.
AB  - Acute skin rejection in vascularized composite allotransplantation (VCA) is the
      major obstacle for wider adoption in clinical practice. This study utilized
      computational modeling to identify biomarkers for diagnosis and targets for
      treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin
      and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants
      without immunosuppression [n = 10] and allografts treated with tacrolimus [n =
      10] were assessed by multiplexed analysis technology. Hierarchical Clustering
      Analysis, Principal Component Analysis, Random Forest Classification and
      Multinomial Logistic Regression models were used to segregate experimental
      groups. Based on Random Forest Classification, Multinomial Logistic Regression
      and Hierarchical Clustering Analysis models, IL-4, TNF-alpha and IL-12p70 were
      the best predictors of skin rejection and identified rejection well in advance of
      histopathological alterations. TNF-alpha and IL-12p70 were the best predictors of
      muscle rejection and also preceded histopathological alterations. Principal
      Component Analysis identified IL-1alpha, IL-18, IL-1beta, and IL-4 as principal
      drivers of transplant rejection. Thus, inflammatory patterns associated with
      rejection are specific for the individual tissue and may be superior for early
      detection and targeted treatment of rejection. 

PMID- 24926999
TI  - Effects of a community intervention on HIV prevention behaviors among men who
      experienced childhood sexual or physical abuse in four African settings: findings
      from NIMH Project Accept (HPTN 043).
AB  - BACKGROUND: There is increased focus on HIV prevention with African men who
      report experiencing childhood sexual (CSA) or physical abuse (CPA). OBJECTIVE: To
      better understand the effects of a community-based intervention (Project Accept
      HPTN 043) on HIV prevention behaviors among men who report CSA or CPA
      experiences. METHODS: Project Accept compared a community-based voluntary mobile
      counseling and testing (CBVCT) intervention with standard VCT. The intervention
      employed individual HIV risk reduction planning with motivational interviewing in
      34 African communities (16 communities at 2 sites in South Africa, 10 in
      Tanzania, and 8 in Zimbabwe). Communities were randomized unblinded in matched
      pairs to CBVCT or SVCT, delivered over 36 months. The post-intervention
      assessment was conducted using a single, cross-sectional random survey of 18-32
      year-old community members (total N = 43,292). We analyzed the effect of the
      intervention on men with reported CSA or CPA across the African sites. Men were
      identified with a survey question asking about having experienced CSA or CPA
      across the lifespan. The effect of intervention on considered outcomes of the
      preventive behavior was statistically evaluated using the logistic regression
      models. RESULTS: Across the sites, the rates of CSA or CPA among men indicated
      that African men reflected the global prevalence (20%) with a range of 13-24%.
      The statistically significant effect of the intervention among these men was seen
      in their increased effort to receive their HIV test results (OR 2.71; CI: (1.08,
      6.82); P: 0.034). The intervention effect on the other designated HIV prevention
      behaviors was less pronounced. CONCLUSION: The effect of the intervention on
      these men showed increased motivation to receive their HIV test results. However,
      more research is needed to understand the effects of community-based
      interventions on this group, and such interventions need to integrate other keys
      predictors of HIV including trauma, coping strategies, and intimate partner
      violence.

PMID- 24927000
TI  - Lignans from the fruit of Schisandra glaucescens with antioxidant and
      neuroprotective properties.
AB  - Two rare 7,8-seco-lignans (1, 2), three new lignan glycosides (3, 4a, 4b), and 10
      known lignans (5-14) were isolated from the fruit of Schisandra glaucescens
      Diels. The absolute configurations of 1 and 2 were determined by comparing their
      experimental and calculated electronic circular dichroism spectra. The molecular
      structures of the new compounds (3, 4a, and 4b), including their absolute
      configurations, were determined using various spectroscopic methods and
      hydrolysis reactions. The antioxidant activities of the isolated compounds were
      tested using 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power
      assays. Compounds 4, 7, 8, 10, 11, and 12 exhibited antioxidant activities of
      varying potential in both assays. Of these compounds, 7 showed the strongest 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, with IC50 values of
      15.7 (150 MUM DPPH) and 34.6 MUM (300 MUM DPPH), respectively, and 4, 12, and 7
      displayed higher total antioxidant activities than Trolox in the ferric reducing
      antioxidant power assay. The neuroprotective effects of these compounds against
      Abeta25-35-induced cell death in SH-SY5Y cells were also investigated. Compounds
      1, 2, 6, 7, 8, 11, and 12 exhibited statistically significant neuroprotective
      effects against Abeta25-35-induced SH-SY5Y cell death compared with the group
      treated only with Abeta25-35. 

PMID- 24927001
TI  - Fibrohistiocytic tumors in a lung transplant patient taking oral capecitabine for
      nonmelanoma skin cancer chemoprevention.

PMID- 24927005
TI  - Long-term efficacy and quality of life assessment for treatment of axillary
      hyperhidrosis with a microwave device.

PMID- 24927008
TI  - Open access sclerotherapy: an alternative technique to treat complex venous
      malformations.

PMID- 24927012
TI  - A rare case of quadruple extramammary Paget's disease including an umbilical
      lesion.

PMID- 24927014
TI  - Computational analysis of cyclophane-based bisthiourea-catalyzed Henry reactions.
AB  - The Henry reaction between benzaldehyde and nitromethane catalyzed by a
      cyclophane-based bisthiourea has been studied with density functional theory [M06
      2X-D3/def2-TZVPP/IEFPCM//TPSS-D2/6-31G(d)/IEFPCM]. The results of our study
      reveal that the transformation involves the reaction of a thiourea-nitronate
      complex with the uncoordinated aldehyde. On the basis of our calculations, the
      formation of the major stereoisomer is kinetically preferred. Employing smaller
      model systems, we show that the observed stereoselectivity arises primarily from
      differences in hydrogen bonding in diastereomeric transition states. 

PMID- 24927013
TI  - Enantiospecific, nickel-catalyzed cross-couplings of allylic pivalates and
      arylboroxines.
AB  - We have developed an enantiospecific, nickel-catalyzed cross-coupling of
      unsymmetric 1,3-disubstituted allylic pivalates with arylboroxines. The success
      of this reaction relies on the use of BnPPh2 as a supporting ligand for the
      nickel(0) catalyst and NaOMe as a base. This method shows excellent functional
      group tolerance and broad scope in both the allylic pivalate and arylboroxine,
      enabling the preparation of 1,3-diaryl allylic products in high yields with
      excellent levels of regioselectivity and stereochemical fidelity. 

PMID- 24927015
TI  - Coinfection with HIV-1 alleviates iron accumulation in patients with chronic
      hepatitis C virus infection.
AB  - Most chronically-infected hepatitis C virus (HCV) patients have increased levels
      of iron in the liver. Iron overload reduces sustained responses to antiviral
      therapy, leading to more rapid progression to liver cirrhosis and the development
      of hepatocellular carcinoma. However, it is still unclear how HIV-1 infection
      affects iron status in patients chronically infected with HCV. The present study
      recruited 227 patients from a village in central China. These patients were
      either monoinfected with HCV (n = 129) or coinfected with HCV/HIV-1 (n = 98).
      Healthy controls (n = 84) were also recruited from the same village. Indicators
      of iron status, such as serum levels of iron, ferritin, and transferrin, total
      iron-binding capacity (TIBC), transferrin saturation (Tfs), and hepcidin, were
      analyzed and compared across the three groups. The results showed that serum
      levels of iron (p = 0.001) and ferritin (p = 0.009) and the Tfs (p = 0.002) were
      significantly higher in HCV-monoinfected patients than in the healthy controls;
      however, there were no differences in iron levels and Tfs between HCV/HIV-1
      coinfected patients and healthy controls. Additionally, although serum hepcidin
      levels in HCV-monoinfected and HCV/HIV-1-coinfected patients were lower (p<0.001)
      than those in health controls, the levels in coinfected patients were higher (p =
      0.025) than those in HCV-monoinfected patients. Serum iron and ferritin levels in
      HCV-monoinfected patients were positively correlated with serum ALT/AST. Serum
      transferrin levels were negatively correlated with ALT/AST levels. The levels of
      iron in the serum of coinfected patients with a CD4+T-cell count <500/ul were
      lower than those in patients with a CD4+T-cell count >=500/ul, whereas serum
      hepcidin levels showed the opposite trend. Taken together, these results suggest
      that coinfection with HIV-1 alleviates iron accumulation caused by chronic HCV
      infection. Our study indicated that determining the status of serum iron and
      other iron-associated parameters will be helpful to understand the complexity of
      alternations in iron distribution in HCV/HIV-1-coinfected patients. 

PMID- 24927016
TI  - The influence of photoreceptor size and distribution on optical sensitivity in
      the eyes of lanternfishes (Myctophidae).
AB  - The mesopelagic zone of the deep-sea (200-1000 m) is characterised by
      exponentially diminishing levels of downwelling sunlight and by the predominance
      of bioluminescence emissions. The ability of mesopelagic organisms to detect and
      behaviourally react to downwelling sunlight and/or bioluminescence will depend on
      the visual task and ultimately on the eyes and their capacity for detecting low
      levels of illumination and intermittent point sources of bioluminescent light. In
      this study, we investigate the diversity of the visual system of the lanternfish
      (Myctophidae). We focus specifically on the photoreceptor cells by examining
      their size, arrangement, topographic distribution and contribution to optical
      sensitivity in 53 different species from 18 genera. We also examine the
      influence(s) of both phylogeny and ecology on these photoreceptor variables using
      phylogenetic comparative analyses in order to understand the constraints placed
      on the visual systems of this large group of mesopelagic fishes at the first
      stage of retinal processing. We report great diversity in the visual system of
      the Myctophidae at the level of the photoreceptors. Photoreceptor distribution
      reveals clear interspecific differences in visual specialisations (areas of high
      rod photoreceptor density), indicating potential interspecific differences in
      interactions with prey, predators and/or mates. A great diversity in
      photoreceptor design (length and diameter) and density is also present. Overall,
      the myctophid eye is very sensitive compared to other teleosts and each species
      seems to be specialised for the detection of a specific signal (downwelling light
      or bioluminescence), potentially reflecting different visual demands for
      survival. Phylogenetic comparative analyses highlight several relationships
      between photoreceptor characteristics and the ecological variables tested (depth
      distribution and luminous tissue patterns). Depth distribution at night was a
      significant factor in most of the models tested, indicating that vision at night
      is of great importance for lanternfishes and may drive the evolution of their
      photoreceptor design. 

PMID- 24927017
TI  - A highly tunable system for the simultaneous expression of multiple enzymes in
      Saccharomyces cerevisiae.
AB  - Control of the expression levels of multiple enzymes in transgenic yeasts is
      essential for the effective production of complex molecules through fermentation.
      Here, we propose a tunable strategy for the control of expression levels based on
      the design of terminator regions and other gene-expression control elements in
      Saccharomyces cerevisiae. Our genome-integrated system, which is capable of
      producing high expression levels over a wide dynamic range, will broadly enable
      metabolic engineering and synthetic biology. We demonstrated that the activities
      of multiple cellulases and the production of ethanol were doubled in a transgenic
      yeast constructed with our system compared with those achieved with a standard
      expression system. 

PMID- 24927019
TI  - The importance of small saphenous vein reflux on chronic venous disease clinic.
AB  - AIM: It is estimated that between 5% to 20% of the adult population in developed
      countries is affected by chronic venous insufficiency (CVI), thus being the most
      frequent vascular disorder. Recent studies show that, in most CVI patients, their
      junctions are competent and the correlated superficial reflux is present along
      the saphenous vein. Objective of the study was to correlate the presence and
      distribution of reflux in the saphenous vein with the signs and symptoms of CVI,
      through CEAP, in female patients. METHODS: Record review of patients with CVI
      signs and symptoms who underwent clinical and ultrasound examinations in order to
      classify them according to CEAP. The sample was divided into three groups
      according to the presence of saphenous vein insufficiency: Group I-SSV, Group II
      GSV, and Group III-SSV and GSV. RESULTS: A total of 312 lower limbs of 259 female
      patients aged between 15 and 85 years were examined. The most prevalent clinical
      classes in the three groups were C2 (44.55%) and C3 (46.48%). Four patterns of
      reflux were identified in isolated SSV, with the highest incidence of proximal
      reflux (69.23%). SPJ impairment was most likely to occur in clinical cases of
      greater severity. Five patterns of reflux were identified in GSV, with the
      proximal one the most prevalent (64.42%). CONCLUSION: There is a correlation
      between the clinical severity of CVI and the reflux along the SSV in association
      with GSV; the risk of moderate to high clinical severity in group III was 3.6
      times higher than in group I and 4.6 times higher than group II.

PMID- 24927018
TI  - Evaluation of the therapeutic potential of bone marrow-derived myeloid suppressor
      cell (MDSC) adoptive transfer in mouse models of autoimmunity and allograft
      rejection.
AB  - Therapeutic use of immunoregulatory cells represents a promising approach for the
      treatment of uncontrolled immunity. During the last decade, myeloid-derived
      suppressor cells (MDSC) have emerged as novel key regulatory players in the
      context of tumor growth, inflammation, transplantation or autoimmunity. Recently,
      MDSC have been successfully generated in vitro from naive mouse bone marrow cells
      or healthy human PBMCs using minimal cytokine combinations. In this study, we
      aimed to evaluate the potential of adoptive transfer of such cells to control
      auto- and allo-immunity in the mouse. Culture of bone marrow cells with GM-CSF
      and IL-6 consistently yielded a majority of CD11b+Gr1hi/lo cells exhibiting
      strong inhibition of CD8+ T cell proliferation in vitro. However, adoptive
      transfer of these cells failed to alter antigen-specific CD8+ T cell
      proliferation and cytotoxicity in vivo. Furthermore, MDSC could not prevent the
      development of autoimmunity in a stringent model of type 1 diabetes. Rather,
      loading the cells prior to injection with a pancreatic neo-antigen peptide
      accelerated the development of the disease. Contrastingly, in a model of skin
      transplantation, repeated injection of MDSC or single injection of LPS-activated
      MDSC resulted in a significant prolongation of allograft survival. The beneficial
      effect of MDSC infusions on skin graft survival was paradoxically not explained
      by a decrease of donor-specific T cell response but associated with a systemic
      over-activation of T cells and antigen presenting cells, prominently in the
      spleen. Taken together, our results indicate that in vitro generated MDSC bear
      therapeutic potential but will require additional in vitro factors or adjunct
      immunosuppressive treatments to achieve safe and more robust immunomodulation
      upon adoptive transfer. 

PMID- 24927020
TI  - Endovenous laser treatment of saphenous veins: is there clinical difference using
      different endovenous laser wavelenghts?
AB  - Endovenous laser treatment (EVLT) is an efficient method to treat incompetent
      saphenous veins with high occlusion rates. Major side effects reported with 810
      nm and 980 nm diode laser are postoperative pain and bruising. Recently laser
      systems with higher wavelengths (WSLWs), associated with new energy delivery
      devices, seem to reduce some side effects previously reported. Aim of this study
      is to verify if there are real clinical advantages in the use of WSLWs, reviewing
      the comparison studies present in the literature. After a search on MEDLINE
      database, a review of all papers concerning WSLWs, was made. Five studies of
      comparison between different wavelength, 810 vs.. 980 nm, 940 vs.. 1320 nm, 810
      vs.. 1320 nm, 980 vs.. 1500 nm and 980 vs.. 1470 nm were found. These studies
      report similar results: the WSLWs produce fewer side effects. New optical fibers
      have also been developed; WSLWs with the use of these new fibers dramatically
      changed the postoperative period, with a reduction of pain and bruising. There is
      no scientific evidence that WSLWs have any effect on long-term outcome, although
      short-term differences have been found for some side effects. Other parameters
      are also important: in particular, LEED and cold tumescent anesthesia are
      critical points. Laser fiber design probably has a significant effect on
      treatment success in the performance of EVLT and also how the energy is delivered
      (pulsing or continuous mode) and the pull-back rate of the laser fiber are
      possible factors affecting complication ratios and pain scores, regardless of the
      type of wavelength used. 

PMID- 24927021
TI  - Computational estimation of the influence of the main body-to-iliac limb length
      ratio on the displacement forces acting on an aortic endograft. Theoretical
      application to Bolton Treovance(r) Abdominal Stent-Graft.
AB  - AIM: The influence of the relative iliac limb length of an endograft (EG) on the
      displacements forces (DF) predisposing to adverse effects are under-appreciated
      in the literature. Therefore, we conducted a computational study to estimate the
      magnitude of the DF acting over an entire reconstructed EG and its counterparts
      for a range of main body-to-iliac limb length (L1/L2) ratios. METHODS: A
      customary bifurcated 3D model was computationally created and meshed using the
      commercially available ANSYS ICEM (Ansys Inc., Canonsburg, PA, USA) software.
      Accordingly, Fluid Structure Interaction was used to estimate the DF. The total
      length of the EG was kept constant, while the L1/L2 ratio ranged from 0.3 to 1.5.
      RESULTS: The increase in L1/L2 slightly affected the DF on the EG (ranging from
      3.8 to 4.1 N) and its bifurcation (4.0 to 4.6 N). However, the forces exerted at
      the iliac sites were strongly affected by the L1/L2 values (ranging from 0.9 to
      2.2 N), showing a parabolic pattern with a minimum for 0.6 ratio. CONCLUSION: It
      is suggested that the hemodynamic effect of the relative limb lengths should not
      be considered negligible. A high main body-to-iliac limb length ratio seems to
      favor hemodynamically a low bifurcation but it attenuates the main body-iliac
      limbs modular stability. Further clinical studies should investigate the relevant
      value of these findings. The Bolton Treovance((r)) device is presented as a
      representative, improved stent-graft design that takes into account these
      hemodynamic parameters in order to achieve a promising, improved clinical
      performance.

PMID- 24927022
TI  - Time course analysis of brachial artery flow mediated dilatation in subjects with
      gingival inflammation.
AB  - AIM: Several investigations report an inverse association between periodontal
      disease and endothelial function measured by brachial artery Flow-Mediated
      Dilatation (FMD) technique. These studies examined endothelial function by using
      the traditional approach to FMD calculation, that is from diameters assessed at
      60 seconds after deflation. Nevertheless, possible relationship between gingival
      inflammation and endothelial dysfunction observed over this temporal threshold
      remains still unexplored. The purpose of our study was to explore the
      relationship between gingival inflammation and endothelial function, by
      considering the time course of brachial FMD. METHODS: Forty-six free-living white
      subjects, participating in a cardiovascular disease prevention campaign, were
      enrolled. FMD was measured at 60s and at 2 and 3 min after forearm ischemia.
      Maximal FMD was calculated (Peak FMD), for each patient. Gingival Index (GI) was
      evaluated as measure of gingival inflammation. RESULTS: In univariate analyses,
      GI was associated with both FMD at 60 sec (r=-0.30, P=0.038) and Peak FMD (r=
      0.41, P=0.004). In multiple regression analyses including GI, age, gender, and
      known risk factors for atherosclerosis, only GI and age were independently and
      inversely associated with Peak FMD and FMD at 60 s, but this association was
      stronger with Peak FMD. Moreover, when we divided subjects on the basis of GI
      value, patients with GI > 1 presented lower Peak FMD and higher prevalence of
      absent FMD. CONCLUSION: The present study extends previous observations about the
      negative effects of periodontal disease on endothelial function, highlighting the
      importance of the evaluation of time course of vascular reactivity.

PMID- 24927023
TI  - Effective management of acute deep vein thrombosis: direct oral anticoagulants.
AB  - Deep vein thrombosis (DVT) is a manifestation of venous thromboembolism (VTE) and
      accounts for most venous thromboembolic events. Although DVT is not directly life
      threatening, thrombi in the proximal veins of the leg can embolize to the lungs
      to form a pulmonary embolism, which may prove rapidly fatal. If untreated, DVT
      can also lead to significant morbidity, including development of post-thrombotic
      syndrome. Among many risk factors, surgery, hospitalization, older age and active
      cancer increase the risk of VTE, and a previous event increases the risk of
      recurrence. Early detection and effective clot resolution are vital in managing
      DVT. Conventional approaches to acute treatment of VTE involve initial fast
      acting parenteral heparin overlapping with and followed by vitamin K antagonist
      therapy. However, vitamin K antagonists have a narrow therapeutic window, require
      regular monitoring, and have multiple food and drug interactions. Results from
      phase III clinical studies involving direct Factor Xa and IIa inhibitors suggest
      that these agents provide an alternative therapeutic option that overcomes some
      of the complications associated with conventional treatment with predictable
      pharmacological properties and convenient dosing schedules. Analysis of data from
      the rivaroxaban EINSTEIN studies also suggests that these agents have the
      potential to improve patient-reported treatment satisfaction and reduce the
      length of hospital stay compared with conventional therapy. This review considers
      these treatment options, suitable treatment durations to prevent recurrence, and
      the management of DVT treatment in challenging patient groups. 

PMID- 24927024
TI  - Effects of a low level laser on periodontal tissue in hypofunctional teeth.
AB  - Malocclusions, such as an open bite and high canines, are often encountered in
      orthodontic practice. Teeth without occlusal stimuli are known as hypofunctional
      teeth, and numerous atrophic changes have been reported in the periodontal
      tissue, including reductions in blood vessels in the periodontal ligament (PDL),
      heavy root resorption, and reduced bone mineral density (BMD) in the alveolar
      bone. Low Level Laser (LLL) has been shown to have a positive effect on bone
      formation and the vasculature. Although the recovery of hypofunctional teeth
      remains unclear, LLL is expected to have a positive influence on periodontal
      tissue in occlusal hypofunction. The aim of the present study was to elucidate
      the relationship between LLL and periodontal tissue in occlusal hypofunction.
      Twenty-four male rats aged 5 weeks were randomly divided into control and
      hypofunctional groups. An anterior metal cap and bite plate were attached to the
      maxillary and mandibular incisors in the hypofunctional group to simulate
      occlusal hypofunction in the molars. LLL irradiation was applied to the maxillary
      first molar through the gingival sulcus in half of the rats. Rats were divided
      into four groups; control, control+LLL, hypofunctional, and hypofunctional+LLL.
      Exposure to LLL irradiation was performed for 3 minutes every other day for 2
      weeks. Animals were examined by Micro-CT at 5 and 7 weeks and were subsequently
      sacrificed. Heads were resected and examined histologically and
      immunohistologically. The hypofunctional group had obvious stricture of the PDL.
      However, no significant differences were observed in the PDL and alveolar bone
      between the hypofunctional+LLL and the control groups. In addition, the
      expression of basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF)-positive cells were higher in the hypofunctional + LLL group
      than in the hypofunctional group. These results indicated that LLL enhanced the
      production of bFGF and VEGF in the periodontal tissue of hypofunctional teeth. 

PMID- 24927025
TI  - Investment in seed physical defence is associated with species' light requirement
      for regeneration and seed persistence: evidence from Macaranga species in Borneo.
AB  - The seed stage is often critical in determining the regeneration success of
      plants. Seeds must survive an array of seed predators and pathogens and germinate
      under conditions favourable for seedling establishment. To maximise recruitment
      success plants protect seeds using a diverse set of chemical and physical
      defences. However, the relationship between these defence classes, and their
      association with other life history traits, is not well understood. Data on seed
      coat thickness and fracture resistance, and the abundance and diversity of
      potential defensive compounds were collected for 10 tree species of Macaranga
      from Borneo. The data were used to test whether there is a trade-off in physical
      versus chemical defence investment, and to determine how investment varies with
      seed mass, and light requirement for regeneration. Across species there was no
      correlation between seed coat thickness and abundance of potential defensive
      compounds, indicating the absence of a direct trade-off between defence classes.
      While chemical defences were not correlated to other traits, physical defences
      were positively correlated with light requirement for regeneration. For a subset
      of five Macaranga species we evaluated the relative investment in chemical and
      physical defence to seed persistence in the soil, measured as the time to half
      initial seed viability (seed half-life). Half-life was negatively related to the
      ratio of potential defensive compound abundance to seed coat thickness,
      suggesting that species with long persistence invested in physical defence more
      than stored chemical defences. These results indicate that investment in seed
      defences are associated with species' light requirements for regeneration, rather
      than scaling positively with seed mass. Furthermore, chemical defences, although
      highly variable among species, do not appear to be critical to long term
      persistence of Macaranga seeds, and may be important in defending seeds from
      natural enemies distinct from those found in the soil. 

PMID- 24927026
TI  - An international perspective and review of cocaine-induced psychosis: a call to
      action.
AB  - Cocaine use can induce transient psychotic symptoms that include suspiciousness,
      paranoia, hallucinations, and other cocaine-related behaviors. In this
      commentary, the authors provide an international perspective while reviewing the
      recent advances in epidemiology, clinical features, and risk factors related to
      cocaine-induced psychosis exhibited by patients with cocaine use disorders. In
      some settings, the occurrence of cocaine-induced psychosis has been shown to be
      as high as 86.5%. Many risk factors have been linked with cocaine-induced
      psychosis, including the quantity of cocaine consumed, lifetime amount of cocaine
      use, onset of cocaine dependence, years of use, routes of administration, other
      substance use disorder comorbidity, weight, gender, comorbidity with other
      medical and mental health disorders, genetics, and pharmacological interactions.
      Research has shown that the evaluation of cocaine-induced psychosis in patients
      with cocaine use is clinically relevant, especially in those patients who consume
      high amounts of cocaine, have a cannabis dependence history, have antisocial
      personality disorder, use administration routes other than intranasal, or exhibit
      attention-deficit/hyperactivity disorder (ADHD) comorbidity. Currently, the
      literature lacks information regarding the evolution of cocaine dependence or
      cocaine-dependent patients' risk for developing schizophrenia or other psychotic
      disorders. Furthermore, clinicians still do not have an evidence-based
      pharmacological approach to management of cocaine dependence available to them.
      Additional research is also needed regarding risk factors such as neurobiological
      markers and personality traits. Finally, we recommend the development of an
      integrative model including all of the risk factors and protective factors for
      cocaine-induced psychosis.

PMID- 24927028
TI  - Angiolipoma of the Orbit: A Rare Tumor in an Unusual Location.
AB  - Despite their relatively frequent occurrence on the trunk and extremities,
      lipomas rarely present in the orbit. Rarer still are variants of lipoma such as
      fibrolipoma, myxoid lipoma, and angiolipoma. The authors report a 66-year-old
      woman who presented with a large, slowly growing tumor of the forehead and orbit.
      The case presentation conforms to the tenets of the Declaration of Helsinki and
      is HIPAA compliant. Clinical and radiographic evidence suggested a lipomatous
      type of tumor, and excisional biopsy revealed adipose proliferation with numerous
      small vessels and fibrin thrombi consistent with angiolipoma. The tumor was
      completely excised without ophthalmic sequelae or recurrence in 6 months of
      follow up. To the authors' knowledge, this tumor represents only the second
      reported case of this type of highly vascularized lipomatous lesion within the
      orbit. This case is a novel entity in the differential diagnosis of orbital
      tumors and demonstrates the value of total excision in such cases. 

PMID- 24927027
TI  - Increased prevalence of chronic lymphocytic thyroiditis in Korean patients with
      papillary thyroid cancer.
AB  - BACKGROUND: In recent years, some reports have suggested that papillary thyroid
      cancers are more frequently associated with lymphocytic thyroiditis or
      Hashimoto's thyroiditis. This study investigated a potential increase in the
      prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer
      patients. MATERIALS AND METHODS: We used national epidemiological survey data on
      thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective
      medical record survey was conducted by representative sampling of a national
      cancer incidence database. The analysis included 5,378 papillary thyroid cancer
      patients aged 20-79 years. We calculated the age-standardized prevalence and age
      adjusted prevalence ratios using a binomial regression model with a log link for
      the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer
      patients by sex for each year. RESULTS: The prevalence of chronic lymphocytic
      thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men
      and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008,
      respectively. Between 1999 and 2008, the age-standardized prevalence of chronic
      lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in
      female patients with papillary thyroid cancer. The prevalence of other thyroid
      diseases, however, did not increase in either gender. CONCLUSIONS: Among Korean
      papillary thyroid cancer patients, the prevalence of chronic lymphocytic
      thyroiditis increased between 1999 and 2008, whereas the prevalence of other
      thyroid disorders did not change.

PMID- 24927029
TI  - Lateral tarsoconjunctival onlay flap lower eyelid suspension in facial nerve
      paresis.
AB  - PURPOSE: To evaluate the efficacy of a lateral tarsoconjunctival flap suspension
      procedure to improve paralytic eyelid malposition. METHODS: Retrospective chart
      review (with photograph and videographic data) of consecutive patients between
      2008 and 2013 with permanent unilateral paralytic eyelid malposition treated with
      a far lateral tarsoconjunctival flap lower eyelid suspension alone or in
      conjunction with lateral canthoplasty. Upper and lower eyelid position,
      lagophthalmos, ocular surface disease, patient satisfaction, and cosmesis were
      recorded before and after intervention. Postoperative complications and
      subsequent management were also recorded. RESULTS: A total of 110 patients were
      identified. Lagophthalmos, ocular surface exposure, exposure keratopathy, and
      eyelid retraction (both upper and lower) improved in all cases. All patients
      described an improvement in eye irritation, epiphora, and cosmesis. Patients with
      a good Bell's reflex exhibited some dynamic function to the lower eyelid on
      videography. Three (2.7%) eyelids had flap dehiscence that was successfully
      treated with repeat suturing. Seven (6.4%) patients had symptomatic temporal
      peripheral vision requiring partial flap takedown. Five (4.5%) patients had
      pyogenic granulomas excised. Seven (6.4%) patients later had a supplemental
      medial tarsorrhaphy for medial lagophthalmos. CONCLUSIONS: The lateral
      tarsoconjunctival flap suspension was highly effective in this series of patients
      with paralytic eyelid malposition. Improved eyelid position and cosmesis were
      universal although some patients benefitted from an additional medial
      tarsorrhaphy. Return of natural upward lower eyelid movement upon eyelid closure
      was a further benefit in some patients. Temporal vision obstruction was an
      infrequent side effect and flap dehiscence and granulomas were rare
      complications.

PMID- 24927030
TI  - The natural history of orbital cavernous hemangiomas.
AB  - PURPOSE: Orbital cavernous hemangiomas (OCH) often present as incidentally found
      asymptomatic lesions, and it has been reported that such lesions do not grow. The
      authors' own experience has been different. They describe the natural history of
      OCH in a cohort with asymptomatic incidentally found lesions and compare them
      with patients with symptomatic OCH to identify any characteristics that might
      predict those which enlarge and produce symptoms. METHODS: This was a
      retrospective comparative case series from 3 tertiary referral orbital centers in
      Australia. There were 104 patients with OCH, 31 of whom presented with
      incidentally found lesions. For patients with incidental lesions, only those with
      a minimum follow-up period of 12 months were included. Outcome measures included
      demographic features, clinical features at presentation and during follow up,
      anatomical location of the OCH, change in maximal linear dimensions of the OCH
      over time, follow-up period, and requirement for treatment in the follow-up
      period. RESULTS: There were 104 patients included in the study. Thirty-one had an
      asymptomatic, incidental OCH on imaging performed for other indications. Seventy
      nine patients had treatment, and 11 of these had presented with an incidental,
      asymptomatic OCH that enlarged and produced symptoms or new clinical findings. In
      the 20 other patients with incidentally found OCH, there was no or minimal change
      in the follow-up period of 1.2 to 20 years (mean 5.8 years, standard deviation
      [SD] 4.6 years). None of the factors analyzed in the study were able to predict
      those patients with an incidental OCH that enlarged and required treatment.
      Patients with incidental lesions that did not grow over several years did not
      change over much longer periods of time. When considering all patients with OCH,
      both incidentally diagnosed and symptomatic, there were 4 factors that predicted
      whether someone with an OCH would require treatment. These were maximal linear
      dimension, male gender, extraconal location (increased risk of requiring
      treatment), and being an incidental finding (decreased risk of requiring
      treatment). CONCLUSIONS: OCH may present as an incidental finding. A significant
      number will grow over time and require treatment. The authors could not identify
      any factor that would predict those lesions that enlarge over time and require
      treatment. If an incidental OCH does not change over several years, it is very
      unlikely to do so in longer periods of follow up.

PMID- 24927031
TI  - Postoperative changes in olfactory function after transcanalicular diode laser
      dacryocystorhinostomy.
AB  - PURPOSE: Transcanalicular diode laser dacryocystorhinostomy (TCL-DCR) is used
      much in recent years for the surgery of nasolacrimal duct obstruction (NLDO).
      Although TCL-DCR is accepted to be minimally invasive, safe, and effective, there
      is no report focusing on postoperative changes in olfactory function after this
      procedure. Hence, the aim of this current study was to investigate the changes in
      olfactory function after TCL-DCR procedure. MATERIALS AND METHODS: This study was
      carried out in 42 volunteers (16 men and 26 women) between the ages of 20 and 81
      years. All participants received detailed lateralized olfactory tests
      preoperatively and at the postoperative first week, first month, third month, and
      sixth month. After lateralized olfactory tests were performed, the results were
      grouped according to the side of the nasal passage where the operation was
      performed for NLDO: the nonoperated side served as the control. RESULTS: The
      current investigation produced 2 major findings: (1) olfactory function decreased
      significantly after TCL-DCR procedure at the operated side of the nose compared
      with the nonoperated side; (2) olfactory abilities of the patients returned to
      normal within 3 months. CONCLUSION: The results of this study showed that
      transcanalicular diode laser could be used safely in terms of olfactory function
      for dacryocystorhinostomy. Temporary decrease of olfactory function on the side
      having TCL-DCR should be taken into account when obtaining informed patient
      consent.

PMID- 24927032
TI  - Contribution of the acetate anion to CO2 solubility in ionic liquids: theoretical
      method development and experimental study.
AB  - A new theoretical method was developed to compute the Henry's law constant for
      gas absorption in a solvent through strong nonphysical interactions. The new
      method was created by expanding the test particle insertion method typically
      applied to physisorbing systems to account for the strong intermolecular
      interactions present in chemisorbing systems. By using an ab initio (AI)-based
      Boltzmann-averaged potential to model the interaction between CO2 and the tetra-n
      butylphosphonium acetate ([P4444][CH3COO]) ionic liquid, the total Henrys's law
      constant at 298 K was computed to be 0.011 to 0.039 bar, reasonably comparable to
      the experimental value of 0.18 bar measured in this work. Three different AI
      potentials were used to verify the applicability of this approach. In contrast,
      when a classical force field (FF) was used to describe the interaction between
      CO2 and [P4444][CH3COO], the Henry's law constant was computed to be 27 bar,
      significantly larger than the experimental value. The classical FF underestimates
      the CO2-[P4444][CH3COO] interaction compared with the AI calculations, which in
      turn leads to the smaller simulated CO2 solubility. Simulations further indicate
      that the CO2 interaction with the [CH3COO](-) anion is much stronger than with
      the [P4444](+) cation. This result strongly suggests that the large CO2
      solubility in [P4444][CH3COO] is due to the strong CO2-[CH3COO](-) interaction. 

PMID- 24927033
TI  - Design, synthesis and glucose uptake activity of some novel glitazones.
AB  - Herein, we report a library consisting of some novel glitazones containing
      thiazolidinedione and its bioisosteres, rhodanine and oxadiazolidine ring
      structures as their basic scaffold for their antidiabetic activity. Twelve novel
      glitazones with diverse chemical structures were designed and synthesized by
      adopting appropriate synthetic schemes and analyzed. Later, subjected to in vitro
      glucose uptake assay in the absence and presence of insulin to confirm their
      antidiabetic activity using rat hemi-diaphragm. The titled compounds exhibited
      glucose uptake activity ranging weak to significant activity. Compounds 4, 5, 9,
      11, 15, 16, 19 and 20 showed considerable glucose uptake activity apart from
      rosiglitazone, a standard drug. Compound 16 happens to be the candidate compound
      from this study to investigate further. The illustration about their design,
      synthesis, analysis and glucose uptake activity is reported here along with the
      in vitro and in silico study based structure-activity relationships. 

PMID- 24927034
TI  - Anammox growth on pretreated municipal wastewater.
AB  - Autotrophic nitrogen removal from municipal wastewater enables development of
      energy autarkic wastewater treatment plants. In this study we report the
      evaluation of the anammox process in a granular sludge fluidized bed lab-scale
      reactor continuously fed with the actual effluent of the A-stage of the WWTP of
      Dokhaven, Rotterdam. The reactor was anoxic, and nitrite was dosed continuously
      to support anammox activity only. The system was operated for more than ten
      months at temperatures between 20 and 10  degrees C. COD was also consumed during
      the process, but heterotrophs could not outcompete anammox bacteria. Volumetric N
      removal rates obtained were comparable or higher than those of conventional N
      removal systems, with values higher than 0.4 g-N L(-1) d(-1) when operated at 10 
      degrees C. The biomass specific N-removal rate at 10  degrees C was on average
      50+/-7 mg-N g-VSS(-1) d(-1) during the last month of operations, almost two times
      higher than previously reported activities at this temperature. FISH analysis
      revealed that the dominant anammox species was Candidatus Brocadia Fulgida
      throughout the experimentation. Evidence for growth of anammox bacteria at
      mainstream conditions was demonstrated for the entire temperature range tested
      (10-20  degrees C), and new granules were shown to be actively formed and
      efficiently retained in the system.

PMID- 24927035
TI  - Engaging with peri-urban woodlands in England: the contribution to people's
      health and well-being and implications for future management.
AB  - In this paper we engage with debates concerning people and their contact with the
      natural environment as part of everyday life drawing on Irwin's ideas of co
      construction and Gibson's theory of affordances. We focus on peri-urban woodlands
      in England as important places where people can interact with nature for health
      and well-being. Qualitative data were collected in situ via walks in the woods,
      focus group discussions and photo elicitation, with a sample of 49 people. These
      methods provide rich data on the wide range of meanings associated with woodlands
      that can have a perceived impact on people's health and well-being. The findings
      link to contemporary debates about health, well-being and ecosystem services. We
      explore the inter-play between attributes of the physical environment and the
      range of facilities provided to enable access, social interactions and the
      benefits people attribute to their woodland experiences. We conclude that peri
      urban woodlands can clearly contribute to self-reported health and well-being in
      multiple ways, and that organized activities can be important for those who face
      barriers to accessing woodlands. A strong message emerging from the research is
      the opportunity afforded by woodlands for social connections with others, as well
      as the provision of a range of sensory benefits and opportunities to observe and
      enjoy seasonal change in woodlands. Mental restoration via connection with nature
      also emerged as important, confirming previous research. 

PMID- 24927036
TI  - Dietary phthalate exposure in pregnant women and the impact of consumer
      practices.
AB  - Phthalates are ubiquitous endocrine-disrupting chemicals that are contaminants in
      food and contribute to significant dietary exposures. We examined associations
      between reported consumption of specific foods and beverages and first trimester
      urinary phthalate metabolite concentrations in 656 pregnant women within a
      multicenter cohort study, The Infant Development and Environment Study (TIDES),
      using multivariate regression analysis. We also examined whether reported use of
      ecofriendly and chemical-free products was associated with lower phthalate
      biomarker levels in comparison to not following such practices. Consumption of
      one additional serving of dairy per week was associated with decreases of 1% in
      the sum of di-2-ethylhexyl phthalate (DEHP) metabolite levels (95% CI: -2.0, 
      0.2). Further, participants who reported sometimes eating homegrown food had
      monoisobutyl phthalate (MiBP) levels that were 16.6% lower (95% CI: -29.5, -1.3)
      in comparison to participants in the rarely/never category. In contrast to
      rarely/never eating frozen fruits and vegetables, participants who reported
      sometimes following this practice had monobenzyl phthalate (MBzP) levels that
      were 21% higher (95% CI: 3.3, 41.7) than rarely/ever respondents. Future study on
      prenatal dietary phthalate exposure and the role of consumer product choices in
      reducing such exposure is needed. 

PMID- 24927038
TI  - Patients' perspective of the design of provider-patients electronic communication
      services.
AB  - Information Delivery is one the most important tasks in healthcare practice. This
      article discusses patient's tasks and perspectives, which are then used to design
      a new Effective Electronic Methodology. The system design methods applicable to
      electronic communication in the healthcare sector are also described. The
      architecture and the methodology for the healthcare service portal are set out in
      the proposed system design. 

PMID- 24927037
TI  - A study of handling cytotoxic drugs and risk of birth defects in offspring of
      female veterinarians.
AB  - We examined the association of occupational exposure to handling cytotoxic drugs
      at work with risk of birth defects among a cohort of female veterinarians. This
      study is a follow up survey of 321 female participants (633 pregnancies) who
      participated in the Health Risks of Australian Veterinarian project. Data on
      pregnancies and exposure during each pregnancy was obtained by self-administered
      mailed questionnaire. Female veterinarians handling cytotoxic drugs during their
      pregnancy had a two-fold increased risk of birth defects in their offspring (RR =
      2.08, 95% CI (1.05-4.15)). Results were consistent in subgroup analysis of those
      who graduated during the period of 1961 to 1980 (RR = 5.04, 95% CI (1.81, 14.03)
      and in those working specifically in small and large animal practice. There was
      no increased risk in the subgroup that graduated after 1980. Women with unplanned
      pregnancies were more likely to handle cytotoxic drugs on a daily basis (RR =
      1.86, 95% CI, 1.00-3.48) and had a higher increased risk of birth defects than
      those who planned their pregnancies in recent graduates and in those who worked
      specifically in small animal practice (RR = 2.53, 95% CI, 1.18-5.42). This study
      suggests that the adverse effects of handling cytotoxic drugs in pregnant women
      may include an increased risk of birth defects. Pregnancy intention status is an
      important health behavior and should be considered in prenatal programs. 

PMID- 24927039
TI  - Effect-directed analysis for estrogenic compounds in a fluvial sediment sample
      using transgenic cyp19a1b-GFP zebrafish embryos.
AB  - Xenoestrogens may persist in the environment by binding to sediments or suspended
      particulate matter serving as long-term reservoir and source of exposure,
      particularly for organisms living in or in contact with sediments. In this study,
      we present for the first time an effect-directed analysis (EDA) for identifying
      estrogenic compounds in a sediment sample using embryos of a transgenic reporter
      fish strain. In the tg(cyp19a1b-GFP) transgenic zebrafish strain, the expression
      of GFP (green fluorescent protein) in the brain is driven by an oestrogen
      responsive element in the promoter of the cyp19a1b (aromatase) gene. The selected
      sediment sample of the Czech river Bilina had already been analysed in a previous
      EDA using the yeast oestrogen screening assay and had revealed fractions
      containing estrogenic compounds. When normal phase HPLC (high performance liquid
      chromatography) fractionation was used for the separation of the sediment sample,
      the biotest with transgenic fish embryos revealed two estrogenic fractions.
      Chemical analysis of candidate compounds in these sediment fractions suggested
      alkylphenols and estrone as candidate compounds responsible for the observed
      estrogenic effect. Alkylphenol concentrations could partially explain the
      estrogenicity of the fractions. However, xenoestrogens below the analytical
      detection limit or non-targeted estrogenic compounds have probably also
      contributed to the sample's estrogenic potency. The results indicated the
      suitability of the tg(cyp19a1b-GFP) fish embryo for an integrated chemical
      biological analysis of estrogenic effects. 

PMID- 24927041
TI  - Bayesian common spatial patterns for multi-subject EEG classification.
AB  - Multi-subject electroencephalography (EEG) classification involves algorithm
      development for automatically categorizing brain waves measured from multiple
      subjects who undergo the same mental task. Common spatial patterns (CSP) or its
      probabilistic counterpart, PCSP, is a popular discriminative feature extraction
      method for EEG classification. Models in CSP or PCSP are trained on a subject-by
      subject basis so that inter-subject information is neglected. In the case of
      multi-subject EEG classification, however, it is desirable to capture inter
      subject relatedness in learning a model. In this paper we present a nonparametric
      Bayesian model for a multi-subject extension of PCSP where subject relatedness is
      captured by assuming that spatial patterns across subjects share a latent
      subspace. Spatial patterns and the shared latent subspace are jointly learned by
      variational inference. We use an infinite latent feature model to automatically
      infer the dimension of the shared latent subspace, placing Indian Buffet process
      (IBP) priors on our model. Numerical experiments on BCI competition III IVa and
      IV 2a dataset demonstrate the high performance of our method, compared to PCSP
      and existing Bayesian multi-task CSP models. 

PMID- 24927040
TI  - Quantitative analysis of signaling networks across differentially embedded tumors
      highlights interpatient heterogeneity in human glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain
      tumor, with a dismal mean survival even with the current standard of care.
      Although in vitro cell systems can provide mechanistic insight into the
      regulatory networks governing GBM cell proliferation and migration, clinical
      samples provide a more physiologically relevant view of oncogenic signaling
      networks. However, clinical samples are not widely available and may be embedded
      for histopathologic analysis. With the goal of accurately identifying activated
      signaling networks in GBM tumor samples, we investigated the impact of embedding
      in optimal cutting temperature (OCT) compound followed by flash freezing in LN2
      vs immediate flash freezing (iFF) in LN2 on protein expression and
      phosphorylation-mediated signaling networks. Quantitative proteomic and
      phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact
      of the different sample processing strategies and highlighted the large
      interpatient heterogeneity present in these tumors. Correlation analyses of the
      differentially processed tumor sections identified activated signaling networks
      present in selected tumors and revealed the differential expression of
      transcription, translation, and degradation associated proteins. This study
      demonstrates the capability of quantitative mass spectrometry for identification
      of in vivo oncogenic signaling networks from human tumor specimens that were
      either OCT-embedded or immediately flash-frozen. 

PMID- 24927042
TI  - Renal fibromuscular dysplasia with malignant hypertension cured by balloon
      angioplasty with stenting.
AB  - We presented a 31-year-old female patient with a history of hypertension and
      severe pulsing headache for about 3 months. The patient had pulsing headaches
      over the past 3 months with increased very high blood pressure (BP = 220/130
      mmHg), sometimes with blurred vision, nausea and vomiting, with no known
      pathological conditions in her medical history or family background. A digital
      subtraction angiography confirmed tight stenosis (90%) in the middle segment of
      the right renal artery. Balloon angioplasty with a stent was the treatment of
      choice. Blood pressure dropped to normal after treatment.

PMID- 24927043
TI  - Fluid resuscitation in trauma patients: what should we know?
AB  - PURPOSE OF REVIEW: Fluid resuscitation in trauma patients could reduce organ
      failure, until blood components are available and hemorrhage is controlled.
      However, the ideal fluid resuscitation strategy in trauma patients remains a
      debated topic. Different types of trauma can require different types of fluids
      and different volume of infusion. RECENT FINDINGS: There are few randomized
      controlled trials investigating the efficacy of fluids in trauma patients. There
      is no evidence that any type of fluids can improve short-term and long-term
      outcome in these patients. The main clinical evidence emphasizes that a
      restrictive fluid resuscitation before surgery improves outcome in patients with
      penetrating trauma. Fluid management of blunt trauma patients, in particular with
      coexisting brain injury, remains unclear. SUMMARY: In order to focus on the state
      of the art about this topic, we review the current literature and guidelines.
      Recent studies have underlined that the correct fluid resuscitation strategy can
      depend on the type of trauma condition: penetrating, blunt, brain injury or a
      combination of them. Of course, further studies are needed to investigate the
      impact of a specific fluid strategy on different type and severity of trauma.

PMID- 24927044
TI  - Lung-protective ventilation in abdominal surgery.
AB  - PURPOSE OF REVIEW: To provide the most recent and relevant clinical evidence
      regarding the use of prophylactic lung-protective mechanical ventilation in
      abdominal surgery. RECENT FINDINGS: Evidence is accumulating, suggesting an
      association between intraoperative mechanical ventilation strategy and
      postoperative pulmonary complications in patients undergoing abdominal surgery.
      Nonprotective ventilator settings, especially high tidal volume (>10-12 ml/kg),
      very low level of positive end-expiratory pressure (PEEP, <5 cm H2O), or no PEEP,
      may cause alveolar overdistension and repetitive tidal recruitment leading to
      ventilator-associated lung injury in patients with healthy lungs. Stimulated by
      the previous findings in patients with acute respiratory distress syndrome, the
      use of lower tidal volume ventilation is becoming increasingly more common in the
      operating room. However, lowering tidal volume, though important, is only part of
      the overall multifaceted approach of lung-protective mechanical ventilation.
      Recent data provide compelling evidence that prophylactic lung-protective
      mechanical ventilation using lower tidal volume (6-8 ml/kg of predicted body
      weight), moderate PEEP (6-8 cm H2O), and recruitment maneuvers is associated with
      improved functional or physiological and clinical postoperative outcome in
      patients undergoing abdominal surgery. SUMMARY: The use of prophylactic lung
      protective ventilation can help in improving the postoperative outcome.

PMID- 24927045
TI  - Development of near infrared reflectance spectroscopy to predict chemical
      composition with a wide range of variability in beef.
AB  - A total of 182 beef samples were minced and divided into calibration set (n=140)
      and independent validation set (n=42). Calibration models of NIRS (1000-1800nm)
      were built using partial least squares regression (PLSR) on the calibration set
      of samples. Both the coefficient of determination in calibration (R(2)C) and the
      coefficient of determination in prediction (R(2)P) were over 0.98 for all
      chemical compositions. The ratio performance deviation (RPD) was 17.37, 5.12 and
      10.43 for fat, protein and moisture, respectively. The results of the present
      study indicate the outstanding ability of NIRS to predict chemical composition in
      beef. 

PMID- 24927046
TI  - Epidemiological evidence for the association between red and processed meat
      intake and colorectal cancer.

PMID- 24927049
TI  - Utility of a redox-active pyridine(diimine) chelate in facilitating two electron
      oxidative addition chemistry at uranium.
AB  - Exposure of the uranium(IV) complex, Cp(P)U((Mes)PDI(Me)) (1) ((Mes)PDI(Me) = 2,6
      ((Mes)N=CMe)2-C5H3N; Mes = 2,4,6-trimethylphenyl; Cp(P) = 1-(7,7
      dimethylbenzyl)cyclopentadienyl), which contains a [(Mes)PDI(Me)](3-) chelate, to
      I2, Cl2, PhSeCl, and PhEEPh (E = S, Se, Te) results in oxidative addition to form
      the uranium(IV) family, Cp(P)U(XX')((Mes)PDI(Me)) (X = X' = I, Cl, EPh; X = SePh,
      X' = Cl). Spectroscopic and structural studies support products with
      [(Mes)PDI(Me)](1-), indicating the reducing equivalents derive from this redox
      active chelate.

PMID- 24927048
TI  - Temperature induced denaturation of myosin: evidence of structural alterations of
      myosin subfragment-1.
AB  - Denaturation of myofibrillar proteins in porcine longissimus thoracis et lumborum
      muscle was investigated after pre-rigor temperature incubation at 20, 30 and 40
      degrees C. At 24h myofibrils were isolated and myosin was further cleaved by
      chymotrypsin. High temperature pre-rigor induced release of myosin S1
      (subfragment-1), less (P < 0.05) Ca(2+)-ATPase activity and structural
      alterations of the region of the myosin molecule that harbors S1. Surface
      hydrophobicity of myofibrils from the 40 degrees C group increased (P<0.001),
      suggesting a temperature-induced structural rearrangement exposing hydrophobic
      groups on the surface of myofibrils which in turn may explain the reduced water
      holding of PSE meat. 

PMID- 24927047
TI  - Effect of dietary supplementation with red wine extract or vitamin E, in
      combination with linseed and fish oil, on lamb meat quality.
AB  - Thirty lambs were assigned to the following treatments: control diet (C) rich in
      omega-3 fatty acids; C plus 900ppm red wine extract (RWE), or C plus 300ppm
      vitamin E (VE). Oxidative stability and sensory properties of chops stored in MAP
      (70% O2/30% CO2) during 12days were evaluated. Chops from the VE group showed
      lower lipid oxidation (p<0.001) and protein carbonylation (p<0.05), stable omega
      3 fatty acids proportions and overall liking sensory scores (p<0.05). Dietary RWE
      supplementation did not influence oxidative stability of chops, however levels of
      C20:5n-3 were greater (p<0.05) and n-6/n-3 ratio (p<0.01) was lower, relative to
      controls. 

PMID- 24927050
TI  - Theoretical characterization and design of highly efficient iridium (III)
      complexes bearing guanidinate ancillary ligand.
AB  - A density functional theory/time-depended density functional theory was used to
      investigate the synthesized guanidinate-based iridium(III) complex
      [(ppy)2Ir{(N(i)Pr)2C(NPh2)}] (1) and two designed derivatives (2 and 3) to
      determine the influences of different cyclometalated ligands on photophysical
      properties. Except the conventional discussions on geometric relaxations,
      absorption and emission properties, many relevant parameters, including spin
      orbital coupling (SOC) matrix elements, zero-field-splitting parameters,
      radiative rate constants (kr) and so on were quantitatively evaluated. The
      results reveal that the replacement of the pyridine ring in the 2-phenylpyridine
      ligand with different diazole rings cannot only enlarge the frontier molecular
      orbital energy gaps, resulting in a blue-shift of the absorption spectra for 2
      and 3, but also enhance the absorption intensity of 3 in the lower-energy region.
      Furthermore, it is intriguing to note that the photoluminescence quantum
      efficiency (PhiPL) of 3 is significantly higher than that of 1. This can be
      explained by its large SOC value<T1|HSO|Sn>(n=3-4) and large transition electric
      dipole moment (MUS3), which could significantly contribute to a larger kr.
      Besides, compared with 1, the higher emitting energy (ET1) and smaller
      <S0|HSO|T1>(2) value for 3 may lead to a smaller non-radiative decay rate.
      Additionally, the detailed results also indicate that compared to 1 with pyridine
      ring, 3 with imidazole ring performs a better hole injection ability. Therefore,
      the designed complex 3 can be expected as a promising candidate for highly
      efficient guanidinate-based phosphorescence emitter for OLEDs applications. 

PMID- 24927051
TI  - Synthesis, biological evaluation and docking study of 3-aroyl-1-(4
      sulfamoylphenyl)thiourea derivatives as 15-lipoxygenase inhibitors.
AB  - A series of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives containing
      sulfonamide moiety were designed and synthesized as 15-lipoxygenase (15-LOX)
      inhibitors. Most synthesized compounds showed potent activity against soybean 15
      LOX with IC50 values less than 25 MUM. The most potent compound 4c (3
      methylbenzoyl derivative) with IC50 value of 1.8 MUM was 10-fold more potent than
      quercetin. Interestingly, compound 4c also showed the highest antioxidant
      activity, as determined by ferric reducing antioxidant power (FRAP) assay. Its
      capacity for reducing ferric ion was more than ascorbic acid. The viability assay
      of the selected compound 4c against oxidative stress-induced cell death in
      differentiated PC12 cells revealed that compound 4c significantly protected
      neurons against cell death in low concentrations.

PMID- 24927053
TI  - 1-Substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their isosteric
      analogs: A new class of selective antitubercular agents active against drug
      susceptible and multidrug-resistant mycobacteria.
AB  - In this work, a new class of highly potent antituberculosis agents, 1-substituted
      5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their oxa and selanyl analogs,
      is described. The minimal inhibitory concentration (MIC) values reached 1 MUM
      (0.36-0.44 MUg/mL) against Mycobacterium tuberculosis CNCTC My 331/88 and 0.25-1
      MUM against six multidrug-resistant clinically isolated strains of M.
      tuberculosis. The antimycobacterial effects of these compounds were highly
      specific because they were ineffective against all eight bacterial strains and
      eight fungal strains studied. Furthermore, these compounds exhibited low in vitro
      toxicity in four mammalian cell lines (IC50 > 30 MUM). We also examined the
      structure-activity relationships of the compounds, particularly the effects on
      antimycobacterial activity of the number and position of the nitro groups, the
      linker between tetrazole and benzyl moieties, and the tetrazole itself.
      Relatively high variability of substituent R(1) on the tetrazole in the absence
      of negative effects on antimycobacterial activity allows further structural
      optimization with respect to toxicity and the ADME properties of the 1
      substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles lead compounds.

PMID- 24927052
TI  - Design, synthesis and biological evaluation of brain targeting l-ascorbic acid
      prodrugs of ibuprofen with "lock-in" function.
AB  - A novel brain targeting l-ascorbic acid derivatives with "lock-in" function were
      designed and synthesized as prodrugs to achieve the effective delivery of
      ibuprofen to brain by glucose transporter 1 (GLUT1) and the Na(+)-dependent
      vitamin C transporter SVCT2. Ibuprofen-loaded four prodrugs were tested in the
      animals. Results from the in vivo distribution study after i.v. administration of
      these four prodrugs and naked ibuprofen indicated that four prodrugs exhibited
      excellent transport ability across the BBB and significantly increased the level
      of ibuprofen in brain. Among them, prodrugs 4 showed higher brain concentration.
      Both biodistribution data and pharmacokinetic parameters suggested that l
      ascorbic acid thiamine disulfide delivery system was a promising carrier to
      enhance CNS drug's delivery ability into brain.

PMID- 24927054
TI  - The use of hairpin DNA duplexes as HIV-1 fusion inhibitors: synthesis,
      characterization, and activity evaluation.
AB  - Discovery of new drugs for the treatment of AIDS that possess unique structures
      associated with novel mechanisms of action are of great importance due the
      rapidity with which drug-resistant HIV-1 strains evolve. Recently we reported on
      a novel class of DNA duplex-based HIV-1 fusion inhibitors modified with
      hydrophobic groups. The present study describes a new category of hairpin fusion
      inhibitor DNA duplexes bearing a 3 nucleotide loop located at either the
      hydrophobic or hydrophilic end. The new loop structures were designed to link 2
      separate duplex-forming oligodeoxynucleotides (ODNs) to make helix-assembly
      easier and more thermally stable resulting in a more compact form of DNA duplex
      based HIV-1 fusion inhibitors. A series of new hairpin duplexes were tested for
      anti-HIV-1 cell-cell membrane fusion activity. In addition, Tm, CD, fluorescent
      resonance energy transfer assays, and molecular modeling analyses were carried
      out to define their structural activity relationships and possible mechanisms of
      action. 

PMID- 24927055
TI  - Multifunctionalization of magnetic nanoparticles for controlled drug release: a
      general approach.
AB  - In this study, a general approach for the multifunctionalization of magnetic
      nanoparticles (MNPs) with drugs (Doxorubicin and Gemcitabine) and targeting
      moieties (Nucant pseudopeptide) for controlled and selective release is
      described. The functionalization is achieved by the formation of disulfide bonds
      between MNPs and drugs derivatives synthesized in this work. Our strategy
      consists in the introduction of a pyridyldisulfide moiety to the drugs that react
      efficiently with sulfhydryl groups of pre-activated MNPs. This approach also
      allows the quantification of the covalently immobilized drug by measuring the
      amount of the 2-pyridinethione released during the process. The linkers developed
      here allow the release of drugs without any chemical modification. This process
      is triggered under highly reducing environment, such as that present inside the
      cells. Complete release of drugs is achieved within 5-8 h under intracellular
      conditions whereas negligible percentage of release is observed in extracellular
      conditions. We propose here a modular general approach for the functionalization
      of nanoparticles that can be used for different types of drugs and targeting
      agents.

PMID- 24927056
TI  - Evaluation of the antiprion activity of 6-aminophenanthridines and related
      heterocycles.
AB  - Series of 6-aminophenanthridines and related heterocyclic compounds such as
      benzonaphtyridines were prepared. Reduction of one of the three aromatic rings
      was also performed. The compounds were first tested for their antiprion activity
      in a previously described yeast-based colourimetric prion assay. The most potent
      derivatives were then assayed ex vivo against the mammalian prion PrP(Sc) in a
      cell-based assay. Several of the new compounds were found more potent than the
      parent lead 6-aminophenanthridine. The most promising compounds against yeast and
      mammalian prions were 8-azido-6-aminophenanthridine (3m), and 7,10
      dihydrophenanthridin-6-amine (14). In the mammalian cell-based assay, the IC50 of
      these two compounds were around 5 MUM and 1.8 MUM, respectively.

PMID- 24927057
TI  - Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido
      complexes.
AB  - Novel Pt(II) complexes of general formula [PtI2(L(1-3))], (C1-C3): where L(1-3)
      are isobutyl, n-pentyl and isopentyl esters of (S,S)-1,3-propanediamine-N,N'-di-2
      (3-cyclohexyl)propanoic acid has been synthesized and characterized by elemental
      analysis, UV/Vis, IR, ((1)H, (13)C and HSQC, Pt) NMR spectroscopy and ESI mass
      spectrometry. Spectroscopic data and computational studies have shown the usual
      square planar coordination geometry of synthesized complexes, with coordination
      of ligands via nitrogen donor atoms. The cytotoxic activity of novel ligands and
      corresponding complexes were investigated on a palette of different cells line.
      Complexes C1-C3 exhibited activity comparable to cisplatin, with IC50 values
      (MUM) ranging from 4.6 +/- 0.6 to 17.2 +/- 2, and showed the highest potential in
      HeLa, LS-174 and EA.hy.926 cells. Ligands L1-L3 exhibited two- to four-times less
      activity than corresponding complexes. Analysis of the mode of action in HeLa
      cells, by ICP-MS study, showed markedly higher intracellular accumulation and DNA
      binding affinity of C1-C3 versus cisplatin, after 4 h and 20 h post-treatment.
      Annexin-V-FITC assay, flow cytometry and fluorescence microscopy study
      demonstrated occurrence of cell death through both apoptotic and necrotic
      changes. Tested complexes, at corresponding IC50 concentrations, caused
      considerable "sub-G1" peak, without other substantial alterations of cell cycle,
      while only C1 induced higher level of phosphatidylserine externalization (11.7%),
      comparing to ligand L1 (4.9%) and cisplatin (8.4%). Structure-activity comparison
      indicated variations of C1-C3 cytotoxicity, related to the drug/ligand
      lipophilicity (C log P value), while intracellular platinum content and DNA
      platination increased on increase of length and branching of ester chain, in
      sequence: C1 (isobutyl) < C2 (n-pentyl) < C3 (isopentyl).

PMID- 24927058
TI  - Plasma high mobility group box 1 protein reflects fibrosis in pediatric
      nonalcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) affects 3-12% of the general pediatric
      population. HMGB1 protein is presently considered a potent inflammatory mediator
      in several liver diseases, even if its role in NAFLD is still unknown in clinical
      studies. Here we investigated the relationships between circulating HMGB1, TGF
      beta and MCP-1 and liver damage in pediatric NAFLD. HMGB1, TGF-beta and MCP-1
      plasma levels were measured in 110 obese children with biopsy-proven NAFLD and 40
      age-matched obese controls. HMGB1, TGF-beta and MCP-1, ALT, AST and cholesterol
      plasma levels were significantly higher in NAFLD than in control children. A
      significant association between increased levels of HMGB1, TGF-beta and MCP-1 and
      high degrees of fibrosis was found. In this study, we showed for the first time
      that circulating levels of HMGB1 were raised in children with NAFLD and strongly
      correlated with fibrosis and systemic inflammation. 

PMID- 24927059
TI  - Multivalent agents containing 1-substituted 2,3,4-trihydroxyphenyl moieties as
      novel synthetic polyphenols directed against HIV-1.
AB  - The synthesis and the assessment of the anti-HIV activity of a set of molecules
      inspired by the multivalent structures of some naturally-occurring polyphenols
      (tannins) are reported. Different multibranched scaffolds have been derived from
      pentaerythritol as the central core which distribute spatially synthetic
      polyphenolic subunits based on 1-substituted 2,3,4-trihydroxyphenyl moieties. A
      tetrapodal compound () bearing four N-(2,3,4-trihydroxyphenyl)amide groups,
      exhibits remarkable selective activity against HIV-1 with EC50 values in the
      micromolar scale, in the same range as those reported for the most representative
      anti-HIV tannins. Preliminary SAR studies emphasize the importance of the 1
      substituted 2,3,4-trihydroxyphenyl moiety, the presence of an amide as the linker
      and the multivalent architecture of these molecules, since the anti-HIV activity
      increases with the number of polyphenolic moieties. The data support the interest
      in synthetic polyphenols and represent a promising starting point for further
      design and development of selective HIV-1 inhibitors. 

PMID- 24927061
TI  - Degradability and cytocompatibility of tricalcium phosphate/poly(amino acid)
      composite as bone tissue implants in orthopaedic surgery.
AB  - In this study, a tricalcium phosphate (TCP) and poly (amino acid) copolymer (PAA)
      biocomposite were fabricated for bone repair and characterized. The results show
      that the compressive strength of the TCP/PAA composites increased with an
      increase in the TCP content at TCP contents less than 40 w%. The weight loss of
      the composite after soaking in phosphate buffered saline for 12 weeks
      significantly increased with an increase in the TCP content, revealing its good
      degradability. In addition, the composite maintained adequate mechanical strength
      during the degradation period because it underwent a surface erosion process. In
      vitro MG63 cell culture experiments showed that the composite is non-cytotoxic
      and thus allows cells to adhere, proliferate and differentiate. Osteoid formation
      was evidenced on the composite surfaces 12 weeks after its implantation into the
      femoral bone of dogs. Furthermore, the composite combined directly with the host
      bone tissue without fibrous capsule tissue, and no inflammatory responses were
      found, showing the good biocompatibility of the composite. It is expected that
      the composite may be used for the development of bone implants for orthopaedic
      surgery.

PMID- 24927062
TI  - Structural diversity and physical properties of paramagnetic molecular conductors
      based on bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) and the
      tris(chloranilato)ferrate(III) complex.
AB  - Electrocrystallization of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) in the
      presence of the tris(chloranilato)ferrate(III) [Fe(Cl2An)3](3-) paramagnetic
      chiral anion in different stoichiometric ratios and solvent mixtures afforded
      three different hybrid systems formulated as [BEDT-TTF]3[Fe(Cl2An)3].3CH2Cl2.H2O
      (1), delta-[BEDT-TTF]5[Fe(Cl2An)3].4H2O (2), and alpha'''-[BEDT
      TTF]18[Fe(Cl2An)3]3.3CH2Cl2.6H2O (3). Compound 1 presents an unusual structure
      without the typical alternating organic and inorganic layers, whereas compounds 2
      and 3 show a segregated organic-inorganic crystal structure where layers formed
      by Lambda and Delta enantiomers of the paramagnetic complex, together with
      dicationic BEDT-TTF dimers, alternate with layers where the donor molecules are
      arranged in the delta (2) and alpha''' (3) packing motifs. Compound 1 behaves as
      a semiconductor with a much lower conductivity due to the not-layered structure
      and strong dimerization between the fully oxidized donors, whereas 2 and 3 show
      semiconducting behaviors with high room-temperature conductivities of ca. 2 S cm(
      1) and 8 S cm(-1), respectively. The magnetic properties are dominated by the
      paramagnetic S = 5/2 [Fe(Cl2An)3](3-) anions whose high-spin character is
      confirmed by electron paramagnetic resonance and magnetic susceptibility
      measurements. The correlation between crystal structure and conductivity behavior
      was studied by means of tight-binding band structure calculations, which support
      the observed conducting properties. 

PMID- 24927060
TI  - Evaluating potential response-modifying factors for associations between ozone
      and health outcomes: a weight-of-evidence approach.
AB  - BACKGROUND: Epidemiologic and experimental studies have reported a variety of
      health effects in response to ozone (O3) exposure, and some have indicated that
      certain populations may be at increased or decreased risk of O3-related health
      effects. OBJECTIVES: We sought to identify potential response-modifying factors
      to determine whether specific groups of the population or life stages are at
      increased or decreased risk of O3-related health effects using a weight-of
      evidence approach. METHODS: Epidemiologic, experimental, and exposure science
      studies of potential factors that may modify the relationship between O3 and
      health effects were identified in U.S. Environmental Protection Agency's 2013
      Integrated Science Assessment for Ozone and Related Photochemical Oxidants.
      Scientific evidence from studies that examined factors that may influence risk
      were integrated across disciplines to evaluate consistency, coherence, and
      biological plausibility of effects. The factors identified were then classified
      using a weight-of-evidence approach to conclude whether a specific factor
      modified the response of a population or life stage, resulting in an increased or
      decreased risk of O3-related health effects. DISCUSSION: We found "adequate"
      evidence that populations with certain genotypes, preexisting asthma, or reduced
      intake of certain nutrients, as well as different life stages or outdoor workers,
      are at increased risk of O3-related health effects. In addition, we identified
      other factors (i.e., sex, socioeconomic status, and obesity) for which there was
      "suggestive" evidence that they may increase the risk of O3-related health
      effects. CONCLUSIONS: Using a weight-of-evidence approach, we identified a
      diverse group of factors that should be considered when characterizing the
      overall risk of health effects associated with exposures to ambient O3.

PMID- 24927064
TI  - The role of lymph node irradiation in the pathogenesis of acquired lymphedema.

PMID- 24927063
TI  - Radix Hedysari polysaccharide suppresses lipid metabolism dysfunction in a rat
      model of non-alcoholic fatty liver disease via adenosine monophosphate-activated
      protein kinase pathway activation.
AB  - Oxidative stress and excess hepatic lipid accumulation contribute to non
      alcoholic fatty liver disease. Radix Hedysari polysaccharides (RHP) have
      attracted interest due to their antioxidant properties and immunomodulatory
      effects. However, the effect of RHP on hepatic lipid metabolism remains to be
      elucidated. In the present study, the response of Sprague-Dawley rat livers to a
      high-fat diet and RHP treatment was investigated by evaluating body weight, liver
      histology, hepatic lipid content, adenosine monophosphate-activated protein
      kinase (AMPK) activity and lipid metabolism gene transcriptional profiles. The
      present study demonstrated that RHP ameliorated lipid metabolism disorders,
      regulated hepatic lipid content, improved liver inflammation and damage,
      activated AMPK via phosphorylation, upregulated peroxisome proliferator-activated
      receptor alpha and downregulated the mRNA expression of sterol regulatory element
      binding protein-1c in rat livers, which reduced lipogenesis and increased
      lipolysis. Taken together, these results suggested that RHP effectively
      ameliorates lipid metabolism disorders in rat livers; thus, RHP may be a
      potential therapeutic agent in the prevention of hepatic steatosis.

PMID- 24927065
TI  - The effectiveness of intermittent pneumatic compression in long-term therapy of
      lymphedema of lower limbs.
AB  - BACKGROUND: The manual lymphatic drainage in lymphedema has proved to be
      successful; however, this method cannot be applied to millions of patients around
      the world. The only solution is to offer inexpensive, easily accessible
      mechanical devices for pneumatic compression (IPC). These devices should be
      designed on parameters of edema fluid hydromechanics. Recent data point to high
      pressures and long time of compression. AIM: To validate the effects of 3 years
      daily high pressure, long inflation time IPC therapy in terms of decrease of limb
      circumference/volume, tissue elasticity, histological changes, and incidental
      complications. METHODS: A group of 18 patients with unilateral leg lymphedema
      stage II to IV was treated for a period of 3 years using an 8-chamber sleeve,
      sequential inflation of chambers to 100-120 mmHg for 50 sec (total 400 sec). Limb
      circumference and tissue tonicity were measured at monthly intervals. Correlation
      between decrease in calf and thigh circumference and increase in elasticity was
      done. RESULTS: The treatment revealed durable permanent decrease of limb
      circumference and increased elasticity of tissues. The improvement was most
      expressed in the calf above the ankle and mid-calf. No complications as thigh
      ring or chronic genital edema were observed. There was no direct correlation
      between the decrease in limb circumference and increase in elasticity, most
      likely due to different mass of fibrous tissue. CONCLUSIONS: IPC takes over the
      permanently missing function of the obliterated lymphatics by squeezing edema
      tissue fluid to the regions with normal lymphatic drainage. The limb
      circumference is decreased or at least does not further increase, elasticity of
      tissue is increased and maintained. No complications in limb tissues were
      observed. The long-term, high pressure IPC, long inflation timed therapy can be
      safely be recommended to patients with lower limb lymphedema.

PMID- 24927068
TI  - Complementary clinical effects of topical tightening treatment in conjunction
      with a radiofrequency procedure.
AB  - Abstract Background: Skin laxity and cellulite on the buttocks and thighs are two
      common cosmetic concerns. Skin tightening with radiofrequency (RF) devices has
      become increasingly popular. OBJECTIVE: The purpose of this study is to evaluate
      the efficacy and safety of a topical skin laxity tightening agent when used in
      combination with an RF device. METHODS: A double-blinded, randomized clinical
      trial enrolled twenty females with mild-to-moderate skin laxity on the posterior
      thighs/buttocks. Each subject underwent two monthly treatments with an RF source
      (Alma Accent) to both legs. Subjects were then randomized to apply a topical
      agent (Skinceuticals Body Tightening Concentrate) twice daily to only one
      designated thigh/buttock throughout the eight-week duration of the study. All
      subjects were evaluated for improvement in lifting, skin tone, radiance,
      firmness/tightness, skin texture, and overall appearance based on photographic
      evaluation by blinded investigators at 12 weeks following the final RF treatment.
      RESULTS: A statistically significant improvement was found in the overall
      appearance on both sides treated with the RF device when compared to baseline.
      However, the area treated with the topical agent showed a statistically
      significantly greater degree of improvement than the side where no topical agent
      was applied. No adverse effects were reported. CONCLUSION: The use of a novel
      skin tightening agent used after RF procedures is both safe and effective for
      treatment of skin laxity on the buttocks and thighs. Combined therapy leads to a
      better result.

PMID- 24927069
TI  - Na+/K+-ATPase beta1-subunit is recruited in Na-K-2Cl co-transporter isoform 2
      multiprotein complexes in rat kidneys: possible role in blood pressure
      regulation.
AB  - OBJECTIVE: The progression from prehypertensive to hypertensive state in
      spontaneous hypertensive rats (SHRs) is accompanied by a significant increase in
      membrane expression of Na-K-2Cl co-transporter isoform 2 (NKCC2), suggesting that
      the altered NKCC2 trafficking and activity are directly related with the
      development of hypertension in this strain. The aim of this work is to gain
      insights on the molecular mechanism that underlies this phenomenon. METHODS: We
      performed a comparative analysis of NKCC2 multiprotein complexes (MPCs) in the
      kidney of SHRs versus Wistar Kyoto rats by Blue Native difference gel
      electrophoresis combined with mass spectrometry. RESULTS: We found that the
      recruitment of the beta-subunit isoform 1 of the Na(+)-K(+)-ATPase (beta1NK) in
      NKCC2 MPCs was significantly increased in the kidneys of SHR compared with Wistar
      Kyoto rat control strain. Co-immunoprecipitation experiments showed that beta1NK
      actually interacts with NKCC2 in the native tissue. The analysis of the
      physiological role of beta1NK-NKCC2 interaction in human embryonic kidney cells
      showed that beta1NK increased the steady-state membrane expression and activity
      of NKCC2 enhancing NKCC2 trafficking toward the plasma membrane. CONCLUSION: We
      identify a new NKCC2-interacting partner involved in the modulation of NKCC2
      intracellular trafficking and possibly involved in the regulation of blood
      pressure.

PMID- 24927070
TI  - Impact of a hospice emergency kit for veterans and their caregivers: a
      prospective cohort study.
AB  - BACKGROUND: Although hospice emergency kits (HEKs) are provided by many home
      hospice agencies, little is known about their use, side effects, and perceived
      impact. OBJECTIVE: To evaluate HEK medication utilization, side effects, and
      impact as perceived by home hospice patients and their caregivers. METHODS: We
      conducted a prospective longitudinal cohort study. Participants included 43
      veterans and their family/caregivers referred to community home hospices with a
      Veterans Affairs (VA)-provided HEK. Measurements included patient/family reports
      based on weekly telephone interviews, electronic medical record (EMR) review, and
      after-death caregiver interviews. RESULTS: The HEK was used by 27 of 43
      patients/caregivers (62.8%). In 11 cases, they reported using the kit on more
      than one occasion. The most commonly used medications were morphine concentrate
      (30.2% of patients), lorazepam (20.9%), and levofloxacin (16.3%). In 15 cases
      (34.9%), the family thought the HEK may have helped the patient stay at home.
      Nineteen of the 43 patients made at least one visit to the emergency department
      (ED) and 22 were hospitalized. Most admissions through the ED were due to
      uncontrolled pain and/or gastrointestinal problems, such as nausea or bowel
      obstruction. In after-death interviews, opinions of the HEK were uniformly
      positive. Respondents described the HEK's usefulness and felt supported and
      empowered by its presence in the home. Minor side effects were reported in four
      cases. CONCLUSIONS: Findings provide promising evidence that HEKs are a feasible
      and well-tolerated method for achieving timely relief of emergent symptoms in
      home hospice patients and possibly avoiding unwanted ED visits and
      hospitalizations.

PMID- 24927071
TI  - Extraction of light trapped due to total internal reflection using porous high
      refractive index nanoparticle films.
AB  - TiO2 nanoparticle layers composed of columnar TiO2 nanoparticle piles separated
      with nanoscale pores were fabricated on the bottom surface of the hemispherical
      glass prism by performing gas phase cluster beam deposition at glancing
      incidence. The porosity as well as the refractive index of the nanoparticle layer
      was precisely tuned by the incident angle. Effective extraction of the light
      trapped in the substrate due to total internal reflection with the TiO2
      nanoparticle layers was demonstrated and the extraction efficiency was found to
      increase with the porosity. An enhanced Rayleigh scattering mechanism, which
      results from the columnar aggregation of the nanoparticles as well as the strong
      contrast in the refractive index between pores and TiO2 nanoparticles in the
      nanoporous structures, was proposed. The porous TiO2 nanoparticle coatings were
      fabricated on the surface of GaN LEDs to enhance their light output. A nearly 92%
      PL enhancement as well as a 30% EL enhancement was observed. For LED
      applications, the enhanced light extraction with the TiO2 nanoparticle porous
      layers can be a supplement to the microscale texturing process for light
      extraction enhancement.

PMID- 24927072
TI  - ShRNA targeting Bmi-1 sensitizes CD44+ nasopharyngeal cancer stem-like cells to
      radiotherapy.
AB  - Accumulating evidence indicates that cancer stem cells (CSCs) are involved in
      resistance to radiation therapy (RT). Bmi-1, a member of the Polycomb family of
      transcriptional repressors, is essential for maintaining the self-renewal
      abilities of stem cells and overexpression of Bmi-1 correlates with cancer
      therapy failure. Our previous study identified that the CD44+ nasopharyngeal
      cancer (NPC) cells may be assumed as one of markers of nasopharyngeal carcinoma
      cancer stem cell-like cells (CSC-LCs) and Bmi-1 is overexpressed in CD44+ NPC. In
      the present study, we used RNA interference technology to knock down the
      expression of Bmi-1 in CD44+ NPC cells, and then measured the radiation response
      by clonogenic cell survival assay. DNA repair was monitored by gammaH2AX foci
      formation. Bmi-1 downstream relative gene and protein expression of p16, p14, p53
      were assessed by western blotting and real-time PCR. Cell cycle and apoptosis
      were detected by flow cytometry assays. We found that Bmi-1 knockdown prolonged
      G1 and enhanced the radiation-induced G2/M arrest, inhibited DNA damage repair,
      elevated protein p16, p14 and p53 expression, leading to increased apoptosis in
      the radiated CD44+ cells. These data suggest that Bmi-1 downregulation increases
      the radiosensitivity to CD44+ NPC CSC-LCs. Bmi-1 is a potential target for
      increasing the sensitivity of NPC CSCs to radiotherapy.

PMID- 24927074
TI  - Stakeholders' perceptions of integrated community case management by community
      health workers: a post-intervention qualitative study.
AB  - BACKGROUND: Integrated community case management (iCCM) involves delivery of
      simple medicines to children with pneumonia, diarrhea and/or malaria by community
      health workers (CHWs). Between 2010 and 2012, an iCCM intervention trial was
      implemented by Healthy Child Uganda. This study used qualitative tools to assess
      whether project stakeholders perceived that iCCM improved access to care for
      children under five years of age. METHODS: The intervention involved training and
      equipping 196 CHWs in 98 study villages in one sub-county in Uganda in iCCM.
      During the eight-month intervention, CHWs assessed sick children, provided
      antimalarials (coartem) for fever, antibiotics (amoxicillin) for cough and fast
      breathing, oral rehydration salts/zinc for diarrhea, and referred very sick
      children to health facilities. In order to examine community perceptions and
      acceptability of iCCM, post-intervention focus groups and key respondent
      interviews involving caregivers, health workers, CHWs and local leaders were
      carried out by experienced facilitators using semi-structured interview guides.
      Data were analyzed using thematic analysis techniques. RESULTS: Respondents
      reported increased access to health care for children as a result of iCCM. Access
      was reportedly closer to home, available more hours in a day, and the
      availability of CHWs was perceived as more reliable. CHW care was reported to be
      trustworthy and caring. Families reported saving money especially due to reduced
      transportation costs, and less time away from home. Respondents also perceived
      better health outcomes. Linkages between health facilities and communities were
      reportedly improved by the iCCM intervention due to the presence of trained CHWs
      in the community. CONCLUSIONS: iCCM delivered by CHWs may improve access to
      health care and is acceptable to families. Policymakers should continue to seek
      opportunities to implement and support iCCM, particularly in remote communities
      where there are health worker shortages.

PMID- 24927075
TI  - Effects of long-term postoperative oral contraceptive use for the prevention of
      endometrioma recurrence on bone mineral density in young women.
AB  - Concerns for negative effects of oral contraceptives (OCs) on bone mineral
      density (BMD) in long-term users have been raised, since OCs suppress the
      hypothalamic-pituitary-ovarian axis. However, there have been still limited data
      regarding the effects of long-term OC use on BMD in young women in the twenties.
      We investigated the effects of long-term OC use for the prevention of
      endometrioma recurrence on BMD in young women. Ninety-two women aged 20-30 years
      who underwent conservative surgery for endometrioma and used postoperative OC for
      at least 12 months to prevent the recurrence were included for this cross
      sectional study, and BMDs after OC use were analyzed. The mean age at starting OC
      and duration of OC use was 25.6 +/- 2.9 years and 40.7 +/- 28.5 months,
      respectively. No correlation was found between BMDs and age at starting OC at all
      sites. In addition, BMDs were also not correlated with the duration of OC use,
      and were comparable according to the dose of OC (20 versus 30 MUg). In
      conclusion, long-term use of OCs has no adverse effect on BMD in post-adolescent
      young women.

PMID- 24927073
TI  - The gatekeeper residue and beyond: homologous calcium-dependent protein kinases
      as drug development targets for veterinarian Apicomplexa parasites.
AB  - Specific roles of individual CDPKs vary, but in general they mediate essential
      biological functions necessary for parasite survival. A comparative analysis of
      the structure-activity relationships (SAR) of Neospora caninum, Eimeria tenella
      and Babesia bovis calcium-dependent protein kinases (CDPKs) together with those
      of Plasmodium falciparum, Cryptosporidium parvum and Toxoplasma gondii was
      performed by screening against 333 bumped kinase inhibitors (BKIs). Structural
      modelling and experimental data revealed that residues other than the gatekeeper
      influence compound-protein interactions resulting in distinct sensitivity
      profiles. We subsequently defined potential amino-acid structural influences
      within the ATP-binding cavity for each orthologue necessary for consideration in
      the development of broad-spectrum apicomplexan CDPK inhibitors. Although the BKI
      library was developed for specific inhibition of glycine gatekeeper CDPKs
      combined with low inhibition of threonine gatekeeper human SRC kinase, some
      library compounds exhibit activity against serine- or threonine-containing CDPKs.
      Divergent BKI sensitivity of CDPK homologues could be explained on the basis of
      differences in the size and orientation of the hydrophobic pocket and specific
      variation at other amino-acid positions within the ATP-binding cavity. In
      particular, BbCDPK4 and PfCDPK1 are sensitive to a larger fraction of compounds
      than EtCDPK1 despite the presence of a threonine gatekeeper in all three CDPKs.

PMID- 24927076
TI  - Assessment of ovarian reserve after unilateral diathermy with thermal doses
      adjusted to ovarian volume.
AB  - Women with polycystic ovary syndrome seem to have a larger ovarian reserve.
      However, regardless of a greater reserve, diminished ovarian reserve has been
      reported after laparoscopic diathermy. The aim of this article was to determine
      whether the doses adjusted unilateral laparoscopic ovarian drilling with
      diathermy (ULOD) diminishes ovarian reserve to compare with bilateral
      laparoscopic ovarian drilling with diathermy (BLOD). Ninety-six women were
      assigned in two groups. One group underwent ULOD receiving thermal doses (0-840 J
      per ovary) adjusted to volume one ovary. The other group underwent BLOD receiving
      fixed doses (600 J per ovary). Ovarian reserve markers [anti-Mullerian hormone
      (AMH); antral follicle count (AFC) and ovarian volume] were measured before and
      after surgery (1 and 6 months). Both groups showed a decrease in AMH after
      surgery, but it was significantly more distinct in the BLOD versus ULOD group
      (2.0 ng/mL versus 1.3 ng/mL; p = 0.018) in the first follow-up month and remained
      significantly different through the sixth follow-up month (1.9 ng/mL versus 1.15
      ng/mL; p = 0.023). In contrast, in the sixth month, the ULOD versus BLOD showed a
      significantly greater increase AFC (p < 0.001) and volume (p = 0.013). Our
      findings evidenced that the dose-adjusted unilateral diathermy (60 J/cm(3)) does
      not have significant and long-term effects on ovarian reserve.

PMID- 24927077
TI  - A new case of maternal phenylketonuria treated with sapropterin dihydrochloride
      (6R-BH4).
AB  - PURPOSE: A woman with phenylketonuria (PKU) was diagnosed through neonatal
      screening, her PAH mutation was p.V388M/p.I65T, for which she received treatment
      with phenylalanine restriction, and was administered oral sapropterin
      dihydrochloride (6R-BH(4)) from the age of thirty. The purpose of this article is
      to describe the treatment with BH4 during her pregnancy and to evaluate a plan
      for its use. METHODS: The patient had an unplanned pregnancy at 34 years of age,
      for which she received a phenylalanine-free supplement enriched with essential
      fatty acids, vitamins and trace elements. RESULTS: The dose of 6R-BH(4) was
      reduced from 500 mg/day to 100 mg/day until its suspension in the 28th week of
      gestation, and was well tolerated. Blood phenylalanine control was easily
      accomplished during this pregnancy, and no nutritional deficiency was seen.
      CONCLUSION: The pregnancy had a normal outcome, and so we consider that
      adaptation of the dose of 6R-BH(4) to the prenatal periods aided a greater
      efficiency and a lower risk in the treatment of maternal PKU.

PMID- 24927078
TI  - Follicular fluid and serum vascular endothelial growth factor, interleukin (IL)
      1beta and glycodelin concentrations: comparison between long-gonadotropin
      releasing hormone (GnRH)-agonist and GnRH-antagonist cycles: a randomized
      controlled trial.
AB  - In this randomized controlled trial, we aimed to examine whether differences
      exist among patients who underwent assisted reproductive technology treatment
      with a long-GnRH-agonist compared to a GnRH-antagonist protocol in terms of
      levels of follicular fluid (FF) and serum concentrations of vascular endothelial
      growth factor (VEGF), glycodelin and interleukin (IL)-1beta on the day of oocyte
      pick-up (OPU). In 80 infertile couple with male factor or unexplained
      infertility, 40 women stimulated with GnRH-antagonist protocol and 40 women with
      the long-GnRH-agonist protocol. FF and blood serum samples were obtained
      simultaneously from 80 women during the OPU procedure and the concentrations of
      VEGF, IL-1beta and glycodelin were measured with commercially available kits.
      Concentrations of FF VEGF, IL-1beta and glycodelin were not significantly
      different in the long-GnRH-agonist and GnRH-antagonist groups, and neither were
      serum concentrations of VEGF, IL-1beta and glycodelin. According to our results
      in at least, we can say that minor differences between these protocols in terms
      of clinical pregnancy do not depend on VEGF, glycodelin or IL-1beta.

PMID- 24927079
TI  - Elevated serum chemerin in Chinese women with hyperandrogenic PCOS.
AB  - OBJECTIVES: To compare serum chemerin levels between women with classic
      hyperandrogenic PCOS, euandrogenic PCOS and matched control subjects. RESEARCH
      DESIGN AND METHODS: This study was carried out at the Second XiangYa Hospital
      between July 2012 and April 2013. Sixty-seven women with PCOS and 20 controls
      were included. Blood pressure, body mass index (BMI), waist to hip ratio (WHR),
      fasting insulin, fasting plasma glucose and blood serum hormone and blood lipid
      were measured. Transvaginal ultrasound was performed. Serum chemerin was measured
      by ELISA. RESULTS: Serum chemerin was significantly higher in classic
      hyperandrogenic PCOS compared with euandrogenic PCOS and controls (311.07 +/-
      141.87 ng/mL versus 228.03 +/- 119.66 ng/mL and 225.87 +/- 86.44 ng/mL, p <
      0.05). Serum chemerin was positively related to follicle count, ovarian volume,
      the level of testosterone, luteinizing hormone/follicle-stimulating hormone, low
      density lipoprotein, triglycerides, fasting blood insulin, insulin resistance by
      homeostasis model assessment, WHR and BMI, while negatively related to the level
      of high-density lipoprotein. Multiple linear regression analyses revealed ovarian
      volumes and WHR were the significant influencing factors of chemerin (p < 0.05).
      The area under the receiver operating characteristic curve for chemerin reached a
      value of 0.684 (0.572-0.796, 95% confidence interval). The best compromise
      between sensitivity (80.0%) and specificity (47.6%) was obtained with a cutoff
      value of 200.94 ng/mL. CONCLUSIONS: Serum chemerin level was increased in Chinese
      women with classic hyperandrogenic PCOS. Serum chemerin measurement offers a
      relatively moderate diagnostic potency with a sensitivity of 80.0% and a
      specificity of 47.6% at 200.94 ng/mL. This suggested that chemerin may be
      involved in the development of the metabolic syndrome of classic PCOS.

PMID- 24927080
TI  - Insulin and body weight but not hyperandrogenism seem involved in seasonal serum
      25-OH-vitamin D3 levels in subjects affected by PCOS.
AB  - PCOS patients were frequently characterized by lower plasma vitamin D levels. The
      mechanisms involved in this dysfunction remains still debated, therefore we
      evaluated the role of androgen, insulin and body weight on the serum VitD levels
      in women with or without PCOS. Eighty one patients 18-42 yrs old were studied
      into "SUMMER" and "WINTER" seasonal period: thirty seven PCOS, seventeen no
      ovarian hyperandrogenic (noPCOS), twelve functional hypothalamic amenorrhea (FHA)
      and finally fifteen healthy (Con). Patients were further divided into: lean (L),
      obese (O), normo- (nINS) and hyperinsulinemic (hINS). All hormonal and metabolic
      parameters were measured at 1-7 days of the menstrual cycle. Our results show
      that VitD levels were lower in PCOS and in noPCOS than in FHA and Con, in
      particular in (O) and (hINS) PCOSs. Both in summer and in winter, PCOSs had basal
      VitD levels significantly lower than FHA and Con, whereas they were similar to
      noPCOS. Yet, LhINS and OPCOS had VitD levels lower than Con and noPCOS. VitD
      levels were comparable in LnINS PCOS and Con. In conclusion, PCOSs had levels of
      VitD lower than controls. Weight and hyperinsulinemia had a significant influence
      on these values. Finally, over 70% of our healthy patients had VitD deficiency.

PMID- 24927082
TI  - Directional properties of fluorenylidene moieties in unsymmetrically substituted
      N-heterocyclic carbenes. Unexpected CH activation of a methylfluorenyl group with
      palladium. Use in palladium catalysed Suzuki-Miyaura cross coupling of aryl
      chlorides.
AB  - Benzimidazolium salts having their two nitrogen atoms substituted by different 9
      alkylfluorenyl groups ( and , alkyl(1)/alkyl(2) = Me/Et, Me/Pr, Me/n-Bu, Me/i-Pr,
      Me/Bn, Me/CH2SMe have been synthesised in high yields in two or three steps from
      N,N'-bis(9H-fluoren-9-ylidene)benzene-1,2-diamine (). The imidazolium salts were
      converted readily into the corresponding PEPPSI-type palladium complexes (PEPPSI
      = pyridine-enhanced precatalyst preparation stabilisation and initiation), while
      reaction of the methylthioether-substituted salt with PdCl2/K2CO3/pyridine
      afforded the palladacycle resulting from metallation of the methyl group attached
      to the fluorenylidene moiety. NMR and X-ray diffraction studies revealed that the
      carbene ligands in behave as clamp-like ligands, the resulting metal confinement
      arising from a combination of the orientational properties of the fluorenylidene
      moieties that push the alkyl groups towards the metal centre and attractive
      anagostic interactions involving CH2(fluorenyl) groups. Complexes were assessed
      in Suzuki-Miyaura cross-coupling reactions. Like their symmetrical analogues they
      displayed high activity in the coupling of phenyl boronic acid with p
      tolylchloride but their performance remained slightly inferior to that of the
      related, symmetrical Et/Et complex . 

PMID- 24927084
TI  - Editorial.

PMID- 24927081
TI  - Early nephrology referral reduces the economic costs among patients who start
      renal replacement therapy: a prospective cohort study in Korea.
AB  - BACKGROUND: The nature of cost-saving effects of early referral to a nephrologist
      in patients with chronic kidney disease (CKD) is not fully evaluated. We
      evaluated the health care costs before and after dialysis according to the
      referral time. METHODS: A total of 879 patients who were newly diagnosed as
      having end-stage renal disease from August 2008 to June 2011 were prospectively
      enrolled. The early referral (ER) group was defined as patients who were referred
      to a nephrologist more than a year before dialysis and had visited a nephrology
      clinic 2 or more times. Patients whose referral time was less than a year were
      considered the late referral (LR) group. Information about medical costs was
      acquired from the claim data of the Korea Health Insurance Review and Assessment
      Service. RESULTS: The total medical costs during the first 12 months after the
      initiation of dialysis were not different between the 526 ER patients and the 353
      LR patients. However, the costs of the ER patients during the first month were
      significantly lower than those of the LR patients (ER vs. LR: 3029 +/- 2219 vs.
      3438 +/- 2821 US dollars [USD], P = 0.025). The total 12-month health care costs
      before the initiation of dialysis were significantly lower in the ER group (ER
      vs. LR: 6206 +/- 5873 vs. 8610 +/- 7820 USD, P<0.001). In the multivariate
      analysis, ER significantly lowered the health care costs during the 12 months
      before (2534.0 +/- 436.2 USD, P<0.001) and the first month (428.5 +/- 172.3 USD,
      P = 0.013) after the initiation of dialysis. CONCLUSIONS: The ER of patients with
      CKD to a nephrologist is associated with decreased medical costs during the
      pretreatment period of renal replacement therapy and the early period of dialysis
      initiation.

PMID- 24927083
TI  - Detection of ozone based on its striking inhibition of tris(1,10
      phenanthroline)ruthenium(II)/glyoxal electrochemiluminescence.
AB  - Ozone unexpectedly dramatically suppresses the electrochemiluminescence (ECL) of
      Ru(phen)3(2+)/glyoxal at an ozone/glyoxal ratio of less than 0.5%. Moreover, a
      sensitive, simple and fast ECL method for ozone detection is developed, with a
      detection time within 1 min and a limit of detection of 20 nM. 

PMID- 24927085
TI  - Focus on social functioning in depression.
AB  - Depressive disorders represent a significant global health burden. By the year
      2020 the contribution of psychiatric and neurological conditions to the global
      burden of disease is predicted to reach 15%. Despite this, depression is
      frequently unrecognized and undertreated; most depressed people do not seek
      treatment for their depression, and of those who do, most do not receive adequate
      treatment. Depression is a debilitating condition and the effects of the illness
      extend beyond the classically defined symptoms to almost every facet of an
      individual's life, including their social interactions; and even beyond the
      individual, to close relatives. The treatment of impaired social functioning has
      not been widely adopted as a therapeutic principle in depression, although it is
      recognized as an important part of the treatment of schizophrenia. However,
      depressed individuals experience more functional impairment than patients with
      other chronic medical conditions such as diabetes and hypertension. Early studies
      have suggested that antidepressants, in addition to improving the core symptoms
      of depression, are effective in the treatment of impaired social functioning; but
      few studies have directly compared different classes of antidepressants. This
      paper seeks to raise awareness of the key issues relating to the treatment of
      impaired social functioning in depression and to provide a basis for wider
      discussion of the topic prior to the establishment of treatment guidelines. 

PMID- 24927086
TI  - Working with the effects of traumatic bereavement by uxoricide (spouse killing)
      on young children's attachment behaviour.
AB  - This is a clinical description of the work of the Traumatic Stress Clinic, London
      with children where one parent kills the other, paying special attention to the
      disorder of attachment which occurs in a majority of the young children. It is
      suggested that this arises from the combination of the extreme trauma of
      witnessing the homicide, the frequent changes of carer, and the relative lack of
      therapeutic help. 

PMID- 24927087
TI  - Combination therapy with nefazodone and lithium: Safety and tolerability in
      fourteen patients.
AB  - Fourteen patients with major depression, resistant to previous pharmacotherapies,
      were treated by the addition of lithium (target range 0.6-0.8 mmol/l) to
      nefazodone (>=400 mg/day) and were prospectively monitored for 6 weeks to assess
      safety and tolerability. There were 42 emergent adverse events-most commonly
      headache, nausea, gastro-intestinal disturbances, tremor, polyuria/polydipsia,
      dry mouth and tiredness. Information on ten additional patients receiving
      combined treatment with lithium and nefazodone was collected by retrospective
      chart review, and it was found that similar adverse events (tremor, dry mouth and
      tiredness) had occurred in these patients. We conclude that when lithium is added
      to nefazodone, new adverse events do occur, but that the treatment is safe and
      tolerable. 

PMID- 24927088
TI  - Comparative efficacy and tolerability among different selective serotonin re
      uptake inhibitors and venlafaxine in a naturalistic setting.
AB  - The objective of this study was to compare, in a naturalistic setting, the
      efficacy and tolerability of currently available Selective Serotonin Reuptake
      Inhibitors (SSRIs) and venlafaxine in outpatients at a primary psychiatric care
      centre in Spain. The sample was composed of 194 patients with mood disorders
      (major depressive disorder or dysthymic disorder according to the DSM-TV
      criteria) who began treatment either with an SSRI (fluoxetine, fluvoxamine,
      paroxetine, sertraline, and citalopram) or with venlafaxine. Baseline severity of
      the mood disorder was assessed using the Hamilton Depression Rating Scale and
      State-Trait Anxiety Inventory, and therapeutic response was measured with the
      Clinical Global Impression for Therapeutic Improvement. Tolerability was assessed
      by recording spontaneously reported adverse experiences. There were no
      significant differences in the efficacy of the antidepressants under study, but
      there were differences in the incidence and profiles of adverse events.
      Fluoxetine was associated with the lowest incidence of adverse effects, in a
      logistical regression model, but particular events seemed to be associated with
      certain treatments: gastrointestinal discomfort (fluvoxamine), tremor
      (sertraline), dry mouth and dizziness (venlafaxine) and sweating and nervousness
      (citalopram). We conclude that in clinical practice there are differences in the
      tolerability of these antidepressants. Studies with bigger samples are needed to
      confirm these findings. 

PMID- 24927089
TI  - Prevalence of severe depression in private practice depressed outpatients.
AB  - The prevalence of severe depression, defined by a score of 50 or less on the
      Global Assessment of Functioning (GAF) scale, and comparisons between severe and
      non-severe depression, were studied in 203 consecutive unipolar and bipolar
      depressed outpatients presenting for treatment of depression in private practice.
      The prevalence of severe degression was 42%. Of the variables investigated
      (unipolar/bipolar diagnosis, age at baseline/onset, gender, atypical features,
      psychotic features, comorbidity, chronicity, recurrences, duration of illness,
      baseline severity), a bipolar I diagnosis and psychotic features were
      significantly more common in severe depression, while comorbidity and recurrences
      were significantly more common in non-severe depression. Contrary to the
      hypothesis that an affective disorder is a progressive illness, the pattern of
      severe depression did not show more recurrences, more chronicity, or a longer
      duration of illness than non-severe depression. The findings might be related to
      the sample studied, as private patients are usually less severely ill than
      patients in public or university hospitals. 

PMID- 24927090
TI  - The QT interval and the atypical antipsychotic, sertindole.
AB  - Sertindole is a limbic-selective antipsychotic agent with a strong affinity for
      D2, 5-HT2 and alpha1-adrenergic receptors. Prolongation of the QT interval and
      other adverse cardiac or cardiovascular reactions are known effects of most
      antipsychotic drugs. For this reason such effects have been extensively monitored
      during clinical trials of sertindole. A small proportion of sertindole-treated
      patients were found to exhibit an increase in QT interval. Detailed analysis
      revealed no increased risk with sertindole of lethal complications due to an
      increase in QT interval. Nevertheless, as with other antipsychotics,
      electrocardiogram (ECG) recordings should be made prior to starting and during
      treatment with sertindole. 

PMID- 24927091
TI  - Is rehospitalization a measure of the efficacy of neuroleptics in the treatment
      of schizophrenia?
AB  - This study was undertaken to evaluate the efficacy of standard neuroleptic
      treatment versus depot neuroleptic treatment. The major criterion for evaluation
      was the number of patients hospitalized. Patients were chosen on the basis of
      their rating by the ICD-10 classification for schizophrenic disorders. The first
      study period was defined as the time when patients were treated with standard
      neuroleptics; the second was when patients were treated with depot neuroleptics.
      There were 231 hospitalizations during the first period, which involved 48
      patients, i.e. 4.8 hospitalizations per patient. The mean total duration of these
      hospitalizations was 5.2 years, i.e. it was on average 5 years before the patient
      was treated with a depot neuroleptic, with 0.93 hospitalizations per year. The
      duration of the second period was the same as the first. Only 44 patients
      remained in the study during this period; their mean number of hospitalizations
      was 7.2 per patient. The mean number of hospitalizations per year per patient was
      1.25. The results suggest that the number of hospitalizations is only a partially
      satisfactory way of evaluating the efficacy of neuroleptic treatments, and
      questions the relative efficacy of depot neuroleptics compared with standard
      neuroleptic treatment. 

PMID- 24927092
TI  - Diagnostic yield of brain CT in a limited-access environment.
AB  - It is not clear why brain CT continues to be used in psychiatric patients in
      spite of reports of a low yield of useful information. Hypoihetically, in
      circumstances (such as in Israel) where access to CT is more limited, clinicians
      will use brain CT more judiciously, resulting in a higher yield. To test this
      hypothesis, we retrieved and reviewed brain CT results and discharge summaries
      for 23 patients with abnormal brain scans, from 91 scans performed at two
      psychiatric inpatient facilities, in order to determine if the brain CT had a
      significant effect on the diagnosis or treatment of the patient. We found no
      indication that the abnormal CT findings had a significant effect on the
      diagnosis or treatment of any of the patients. 

PMID- 24927093
TI  - Anaesthesia in ECT.
AB  - In this retrospective study, the effect of ECT treatment of 53 patients who
      received either propofol or methohexitone for the induction of anaesthesia was
      reviewed. There was no evidence to suggest that patients who received ECT under
      propofol required additional ECT applications, despite the fact that the duration
      of seizure was significantly shorter than with methohexitone. Differences in the
      recorded clinical outcome following ECT course were not statistically
      significant. As propofol is known to result in less cognitive impairment post
      anaesthesia (hence its suitability in day surgery cases), a major problem is how
      to assess this benefit, in the light of the increased cognitive impairment
      produced by having a higher stimulus. 

PMID- 24927094
TI  - An empirical operationalization study of DSM-IV diagnostic criteria for premature
      ejaculation.
AB  - The DSM-IV diagnostic criteria for premature ejaculation remain to be
      investigated by a clinical study. A prospective study was therefore conducted to
      investigate the DSM-IV definition and to provide an empirical operationalization
      of premature ejaculation. In this study 140 men suffering from lifelong premature
      ejaculation were interviewed separately from their partners. Various means of
      assessing the intravaginal ejaculation latency time (IELT) were compared:
      assessment by spontaneous answer, by questionnaire, by imagining foreplay and
      intercourse and estimating the ejaculation time without a clock or with a clock,
      and by stop-watch measurement at home over a one-month period. The number of
      thrusts and feelings of control during foreplay and intercourse were also
      assessed. A total of 110 men used the stop-watch method. Ninety percent of all
      the subjects ejaculated within one minute of intromission, with 80% actually
      ejaculating within 30 seconds. The age of the men and duration of their
      relationship were not correlated with IELT; however, the IELT tended to be longer
      for couples who had a higher frequency of intercourse. There was only a moderate
      correlation between the various methods of assessing IELT. The results suggest
      that premature ejaculation could be operationally defined as an IELT < 1 min in
      more than 90% of episodes of sexual intercourse, independent of age and duration
      of relationship. 

PMID- 24927095
TI  - Should parents take charge of their child's eating disorder? Some preliminary
      findings and suggestions for future research.
AB  - The treatment of children and young adolescents with anorexia nervosa is
      facilitated, relative to the treatment of adult patients, by the possibility of
      enlisting parents as allies in gaining control over eating behaviour. Experience
      at Rhodes Farm Clinic suggests that the capacity for parents to be firm with
      their child enhances weight maintenance following inpatient treatment. Our
      treatment approach is outlined, and illustrated with some clinical material. A
      pilot study of 59 cases (58 females, 1 male) strongly confirms that weight
      maintenance is positively associated with parental firmness, and also negatively
      associated with age on admission to the Clinic. 

PMID- 24927096
TI  - Depression and porphyria: Safe use of fluoxetine in a woman with learning
      disabilities.
AB  - Many antipsychotic and antidepressant drugs can precipitate life-threatening
      porphyric crisis in individuals with the underlying condition. However, when
      people with porphyria develop mental illness, they require treatment in order to
      maintain their quality of life. For this reason, although the condition is rare,
      psychiatrists need information regarding the safety profile of psychotropic drugs
      when used in people with porphyria. This case report describes the safe use of
      fluoxetine to treat depression in a woman with severe learning disabilities and
      porphyria, who failed to respond to non-pharmacological approaches. 

PMID- 24927097
TI  - Adapting to needs in old-age psychiatry.
AB  - The patient described is a 56-year-old man presenting with chronic depression and
      eventually found to have Alzheimer's disease. Issues in the diagnosis and
      evolution of early dementia are discussed. The importance of long-term
      psychological support to the dementing patient, as well as their carers, is
      emphasized. 

PMID- 24927098
TI  - A patient who changed my practice: The lady with a plumher in her roof.
AB  - The psychotic elderly patient described in this paper resisted treatment because
      her delusional beliefs gave her life some purpose and meaning. This case
      illustrates that clinicians need to be mindful that psychotic symptoms can serve
      an adaptive function for patients, and their removal may leave them with a void
      in their lives that they find difficult to tolerate. 

PMID- 24927101
TI  - Structural features and antioxidant activities of lignins from steam-exploded
      bamboo (Phyllostachys pubescens).
AB  - An environmentally friendly steam explosion process of bamboo, followed by alkali
      and alkaline ethanol delignification, was developed to fractionate lignins.
      Results showed that after steam explosion the lignins isolated showed relatively
      low carbohydrate contents (0.55-1.76%) and molecular weights (780-1050 g/mol).
      For each steam-exploded sample, alkali-extracted lignins presented higher
      phenolic OH values (1.41-1.82 mmol/g), p-coumaric acid to ferulic acid ratios
      (pCA/FA ratios 4.5-14.1), and syringyl to guaiacyl ratios (S/G ratios 5.0-8.5)
      than those from alkaline ethanol-extracted lignins (phenolic OH 0.85-1.35 mmol/g,
      pCA/FA ratios 1.6-5.2, and S/G ratios 3.5-4.8). The lignins obtained consisted
      mainly of beta-O-4' linkages combined with small amounts of beta-beta', beta-5',
      and alpha-O-4/beta-O-4 linkages. Antioxidant activities of the lignins obtained
      were tested by the 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azobis(3
      ethylbenzothiazoline-6-sulfonic acid), and ferric reducing activity power
      methods. It was found that alkali-extracted lignins obtained during the initial
      extraction process had higher antioxidant activities than alkaline ethanol
      extracted lignins obtained during the second extraction process. 

PMID- 24927100
TI  - ROP18 is a key factor responsible for virulence difference between Toxoplasma
      gondii and Neospora caninum.
AB  - Toxoplasma gondii (T. gondii) and Neospora caninum (N. caninum) are both obligate
      intracellular protozoan parasites and share many common morphological and
      biological features. Despite these similarities the two parasites differ
      dramatically in virulence in mice, but the factors involved in virulence
      differences between the two parasites remain unknown. A secreted serine-threonine
      kinase called rhoptry protein 18 (ROP18) was identified to play a crucial role on
      virulence differences among different T. gondii clonal lineages. Intriguingly, we
      found that ROP18 in Nc1 strain of N. caninum (NcROP18) is a pseudogene due to
      several interrupting stop codons in the sequence in our previous studies. We
      assume that the difference of ROP18 leads to virulence difference between T.
      gondii and N. caninum. We constructed a transgenic N. caninum Nc1 stain by
      transfecting the TgROP18 from the T. gondii RH strain. Phenotype and virulence
      assays showed that the expression of TgROP18 in N. caninum did not affect the
      motility and cell invasion, but resulted in a significant increase in
      intracellular parasite proliferation and virulence in mice. Immunity-Related
      GTPase (IRG) phosphorylation assay showed that the transgenic parasite Nc1
      TgROP18 was able to phosphorylate IRGs as T. gondii did. The present study
      indicated that the ROP18 plays a crucial role in virulence of the closely related
      parasites T. gondii and N. caninum and it is indeed a key factor responsible for
      the virulence difference between T. gondii and N. caninum. 

PMID- 24927103
TI  - Yellow/orange emissive heavy-metal complexes as phosphors in monochromatic and
      white organic light-emitting devices.
AB  - Owing to the electron spin-orbit coupling (SOC) and fast intersystem crossing
      (ISC), heavy-metal complexes (such as iridium(III), platinum(II) and osmium(II)
      complexes, etc.) are phosphorescent emitters at room temperature. Since 1998,
      heavy-metal complexes as phosphors have received considerable academic and
      industrial attention in the field of organic light-emitting diodes (OLEDs),
      because they can harvest both the singlet (25%) and triplet (75%) excitons for
      emission during the electro-generated processes. Among all the visible colors
      (blue, green, yellow, orange and red), the yellow/orange heavy-metal complexes
      play an important role for realizing full-color OLEDs as well as high-efficiency
      white OLEDs, and thus the development of highly efficient yellow/orange heavy
      metal complexes is a pressing concern. In this article, we will review the
      progress on yellow/orange heavy-metal complexes as phosphors in OLEDs. The
      general principles and useful tactics for designing the yellow/orange heavy-metal
      complexes will be systematically summarized. The structure-property relationship
      and electrophosphorescence performance of the yellow/orange heavy-metal complexes
      in monochromatic phosphorescent OLEDs (PhOLEDs) and white OLEDs (WOLEDs) will be
      comprehensively surveyed and discussed.

PMID- 24927102
TI  - TCDD promotes lung tumors via attenuation of apoptosis through activation of the
      Akt and ERK1/2 signaling pathways.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species
      carcinogen that induces cancer in multiple organs. The molecular mechanisms
      underlying TCDD-induced lung tumorigenesis remain unclear. In the present study,
      a two-stage lung tumorigenesis model was established by administrating a single
      low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with
      TCDD to female A/J mice. The results indicated that TCDD combined with low-dose
      NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK
      alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one
      of the tumor-promoting mechanisms regulated by TCDD. We performed an additional
      series of experiments in the normal human bronchial epithelial cell line Beas2B
      cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our
      in vitro results confirmed that TCDD could rescue cells from apoptosis induced by
      staurosporine. The inhibition of apoptosis is likely mediated by the activation
      of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway
      specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In
      conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and
      revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part,
      through the Akt and ERK1/2 signaling pathways. 

PMID- 24927105
TI  - Determination of flowable liquid retention potential of aluminometasilicate
      carrier for liquisolid systems preparation.
AB  - Abstract Context: Liquisolid systems are modern formulations used to increase the
      bioavailability of poorly water-soluble drugs. Their preparation is based on the
      sorption of a drug in liquid state onto a carrier with a high adsorption
      capacity. The carrier particles are subsequently coated with material having a
      large surface area to form free-flowing powder. The main principle of
      bioavailability increasing is based on the presence of the dissolved drug, which
      is ready for immediate absorption in GI tract. Objective: Determination of
      capability of aluminometasilicate carrier Neusilin(r) US2 to adsorb different
      solvents. Materials and methods: The maximum amounts of polyethylene glycol 200
      (PEG 200), polyethylene glycol 400 and propylene glycol (PG), which can be sorbed
      by Neusilin(r) US2, while maintaining an acceptable flowability of the powder
      mixture, were evaluated using determination of the flowable liquid retention
      potential. Results and discussion: From the evaluation of liquisolid powder
      mixtures, it could be observed that 1 g of Neusilin(r) US2 can retain up to 1.00
      g of PG, 1.16 g of polyethylene glycol 400 and 1.48 g of PEG 200, while
      maintaining acceptable flowing properties. Conclusion: Large specific surface
      area in combination with a high absorption capacity makes Neusilin(r) US2
      suitable carrier for liquisolid system preparation.

PMID- 24927104
TI  - HBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and
      increased expression of hBD-2 by DNA demethylation and gene transfection inhibits
      cell proliferation and invasion.
AB  - Human beta-defensin-2 (hBD-2) is a type of epithelial antimicrobial peptide. The
      expression level of hBD-2 mRNA is lower in oral carcinoma cells (OCCs) than in
      healthy oral epithelium. Yet, it is still unknown how hBD-2 expression is
      downregulated in OCCs. The present study investigated DNA hypermethylation of hBD
      2 in OCCs and the effect of the demethylation and increased expression of hBD-2
      on cell proliferation and invasion. Six different types of oral carcinoma cell
      lines (OSC-19, BSC-OF, SAS, HSC-2, HSC-4 and HSY) and normal oral keratinocytes
      (NOKs) were used. The expression levels of hBD-2 in all OCCs were significantly
      lower than that in the NOKs. Treatment with DNA methyltransferase inhibitor, 5
      aza-dC, at the concentration of 50 uM significantly induced upregulation of
      expression of hBD-2 in the OCCs. Using methylation-specific PCR, DNA
      hypermethylation was observed in all OCCs. These results suggest that DNA
      hypermethylation is, at least in part, involved in the decreased expression of
      hBD-2 in OCCs. We examined the effect of 5-aza-dC on the cell proliferation and
      invasive ability of OCCs. The cell invasion assays showed that the number of OCCs
      treated with 5-aza-dC on the filters was significantly lower than that of the
      controls. We examined whether increased expression of hBD-2 generated by gene
      transfection inhibited the proliferation and invasion of SAS cells. The number of
      SAS cells exhibiting increased expression of hBD-2 on the filters in the invasion
      assay were significantly lower on day 7 when compared with the control. hBD-2 may
      function as a tumor suppressor. Increased expression of hBD-2 induced by
      demethylation or increased expression generated by gene transfection may be
      useful therapeutic methods for oral carcinoma. 

PMID- 24927106
TI  - A New Sonographic Weight Estimation Formula for Fetuses with Congenital
      Diaphragmatic Hernia.
AB  - PURPOSE: The accuracy of the sonographic weight estimation (WE) of fetuses with
      congenital diaphragmatic hernia (CDH) is significantly lower than that of fetuses
      without any malformations. The objective of this study was to develop and
      evaluate the first specific sonographic weight formula for fetuses with CDH.
      MATERIALS AND METHODS: In a retrospective, multicenter, cohort study, a
      statistical estimation technique known as "multivariable fractional polynomial
      regression" was applied to a group of 146 fetuses with CDH. Each fetus underwent
      an ultrasound examination with complete biometric parameters within 7 days of
      delivery. A new formula was derived using the obtained data and was then compared
      with other commonly used equations. The accuracy of the different formulas was
      compared using means of signed percentage errors (SPE), medians of absolute
      percentage errors (MAPE), and fractions of estimates within prespecified error
      bounds. RESULTS: The new derived formula is: EFW = 10^(4.6729 107 371 + 0.2365
      011 768 * HC + 0.2228 897 682 * FL^2 - 0.0129 895 773 * FL^3 - 1.0470 039 072 *
      (FL * HC)^0.5 + 0.0004 314 661 * (AC * HC) - [in case of liver herniation] 0.0062
      112 122), where EFW is the estimated fetal weight, HC is the head circumference,
      AC is the abdominal circumference, and FL is the femur length. The new formula
      proved to be superior to other established equations, showing both the lowest
      median absolute percentage error (MAE: 6.97) and mean signed percentage error
      (SPE: 0.40), and the best distribution of absolute percentage errors within
      prespecified error bounds. CONCLUSION: This new formula significantly improves
      weight estimation in fetuses with CDH.

PMID- 24927107
TI  - Virtue training in medical schools: the perspective of behavioral science course
      directors.
AB  - Although the multidisciplinary research on physician socialization has focused on
      areas such as developments in learners' ideological commitments and ethics
      knowledge and skills, the literature on physician virtues has been anecdotal. To
      contribute empirical knowledge of virtue development during socialization, I
      performed constant comparisons on interviews with 20 directors of preclinical
      behavioral science courses. In discussing their courses, participants revealed
      foci on virtues involved in making intimate connections with patients (e.g.,
      empathy) and "being professional" with colleagues (e.g., trustworthiness). To
      cultivate virtues for intimate connections, participants used the strategies of
      learner engagement with patients' narratives of illness, service in underserved
      communities, and shadowing and observing role models. To develop virtues for
      being professional, participants used the strategy of small learner groups, which
      consisted of discussions, project collaborations, and group evaluations. I
      conclude with implications for training students of various health sciences and
      managing health care teams. 

PMID- 24927108
TI  - Diabetes and the Affordable Care Act.
AB  - The Affordable Care Act--"Obamacare"--is the most important federal medical
      legislation to be enacted since Medicare. Although the goal of the Affordable
      Care Act is to improve healthcare coverage, access, and quality for all
      Americans, people with diabetes are especially poised to benefit from the
      comprehensive reforms included in the act. Signed into law in 2010, this massive
      legislation will slowly be enacted over the next 10 years. In the making for at
      least a decade, it will affect every person in the United States, either directly
      or indirectly. In this review, we discuss the major changes in healthcare that
      will take place in the next several years, including (1) who needs to purchase
      insurance on the Web-based exchange, (2) the cost to individuals and the rebates
      that they may expect, (3) the rules and regulations for purchasing insurance, (4)
      the characteristics of the different "metallic" insurance plans that are
      available, and (5) the states that have agreed to participate. With both tables
      and figures, we have tried to make the Affordable Care Act both understandable
      and appreciated. The goal of this comprehensive review is to highlight aspects of
      the Affordable Care Act that are of importance to practitioners who care for
      people with diabetes by discussing both the positive and the potentially negative
      aspects of the program as they relate to diabetes care.

PMID- 24927109
TI  - Capturing the optical phase response of nanoantennas by coherent second-harmonic
      microscopy.
AB  - The ultrafast coherent control of light localization in resonant plasmonic
      nanostructures is intricately related to the phase response of the involved
      plasmon resonances. In this work, we exploit the second harmonic signal generated
      by single optical nanoantennas subject to broadband phase-controlled femtosecond
      pulses to study and tailor the coherent resonance response. Our results reveal
      that both the spectral phase and the amplitude components associated with the
      plasmon resonance of arbitrary individual nanoantennas can be accurately
      determined. 

PMID- 24927111
TI  - Preparation and characterization of TiO2 barrier layers for dye-sensitized solar
      cells.
AB  - A TiO2 barrier layer is critical in enhancing the performance of dye-sensitized
      solar cells (DSSCs). Two methods to prepare the TiO2 barrier layer on fluorine
      doped tin dioxide (FTO) surface were systematically studied in order to minimize
      electron-hole recombination and electron backflow during photovoltaic processes
      of DSSCs. The film structure and materials properties were correlated with the
      photovoltaic characteristics and electrochemical properties. In the first
      approach, a porous TiO2 layer was deposited by wet chemical treatment of the
      sample with TiCl4 solution for time periods varying from 0 to 60 min. The N719
      dye molecules were found to be able to insert into the porous barrier layers. The
      20 min treatment formed a nonuniform but intact TiO2 layer of ~100-300 nm in
      thickness, which gave the highest open-circuit voltage VOC, short-circuit
      photocurrent density JSC, and energy conversion efficiency. But thicker TiO2
      barrier layers by this method caused a decrease in JSC, possibly limited by lower
      electrical conductance. In the second approach, a compact TiO2 barrier layer was
      created by sputter-coating 0-15 nm Ti metal films on FTO/glass and then oxidizing
      them into TiO2 with thermal treatment at 500  degrees C in the air for 30 min.
      The dye molecules were found to only attach at the outer surface of the barrier
      layer and slightly increased with the layer thickness. These two kinds of barrier
      layer showed different characteristics and may be tailored for different DSSC
      studies. 

PMID- 24927110
TI  - Enterobactin-mediated delivery of beta-lactam antibiotics enhances antibacterial
      activity against pathogenic Escherichia coli.
AB  - The design, synthesis, and characterization of enterobactin-antibiotic
      conjugates, hereafter Ent-Amp/Amx, where the beta-lactam antibiotics ampicillin
      (Amp) and amoxicillin (Amx) are linked to a monofunctionalized enterobactin
      scaffold via a stable poly(ethylene glycol) linker are reported. Under conditions
      of iron limitation, these siderophore-modified antibiotics provide enhanced
      antibacterial activity against Escherichia coli strains, including uropathogenic
      E. coli CFT073 and UTI89, enterohemorrhagic E. coli O157:H7, and enterotoxigenic
      E. coli O78:H11, compared to the parent beta-lactams. Studies with E. coli K-12
      derivatives defective in ferric enterobactin transport reveal that the enhanced
      antibacterial activity observed for this strain requires the outer membrane
      ferric enterobactin transporter FepA. A remarkable 1000-fold decrease in minimum
      inhibitory concentration (MIC) value is observed for uropathogenic E. coli CFT073
      relative to Amp/Amx, and time-kill kinetic studies demonstrate that Ent-Amp/Amx
      kill this strain more rapidly at 10-fold lower concentrations than the parent
      antibiotics. Moreover, Ent-Amp and Ent-Amx selectively kill E. coli CFT073 co
      cultured with other bacterial species such as Staphylococcus aureus, and Ent-Amp
      exhibits low cytotoxicity against human T84 intestinal cells in both the apo and
      iron-bound forms. These studies demonstrate that the native enterobactin platform
      provides a means to effectively deliver antibacterial cargo across the outer
      membrane permeability barrier of Gram-negative pathogens utilizing enterobactin
      for iron acquisition. 

PMID- 24927112
TI  - miR-137 regulates the migration of human umbilical vein endothelial cells by
      targeting ephrin-type A receptor 7.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs, which negatively regulate gene
      expression. Post-transcriptional regulation by miRNAs is important for organism
      development. In addition, endothelial cells are key regulators of angiogenesis.
      By using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),
      migration and gelatin sponge-chorioallantoic membrane assays, it was demonstrated
      that when miR-137 was overexpressed, cell viability and migration decreased. In
      addition, it was observed that blocking endogenous miR-137 increased cell
      viability and migration. Bioinformatics analysis indicated that the 3'
      untranslated region (3'UTR) of the ephrin type-A receptor 7 (EPHA7) has a
      putative binding site for miR-137. miR-137 is able to directly bind to the EPHA7
      3'UTR and negatively regulate the expression of EPHA7. miR-137 is also able to
      decrease the growth and migration of human umbilical vein endothelial cells
      (HUVECs). The identification of the function of miR-137 and its target gene EPHA7
      in HUVECs may provide novel insights into the mechanisms of angiogenesis.

PMID- 24927113
TI  - Ru(II) dyads derived from 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline:
      versatile photosensitizers for photodynamic applications.
AB  - Combining the best attributes of organic photosensitizers with those of
      coordination complexes is an elegant way to achieve prolonged excited state
      lifetimes in Ru(II) dyads. Not only do their reduced radiative and nonradiative
      rates provide ample time for photosensitization of reactive oxygen species at low
      oxygen tension but they also harness the unique properties of (3)IL states that
      can act as discrete units or in concert with (3)MLCT states. The imidazo[4,5
      f][1,10]phenanthroline framework provides a convenient tether for linking pi
      expansive ligands such as pyrene to a Ru(II) scaffold, and the stabilizing
      coligands can fine-tune the chemical and biological properties of these
      bichromophoric systems. The resulting dyads described in this study exhibited
      nanomolar light cytotoxicities against cancer cells with photocytotoxicity
      indices exceeding 400 for some coligands employed. This potency extended to
      bacteria, where concentrations as low as 10 nM destroyed 75% of a bacterial
      population. Notably, these dyads remained extremely active against biofilm with
      light photocytotoxicities against these more resistant bacterial populations in
      the 10-100 nM regime. The results from this study demonstrate the versatility of
      these highly potent photosensitizers in destroying both cancer and bacterial
      cells and expand the scope of compounds that utilize low-lying (3)IL states for
      photobiological applications. 

PMID- 24927114
TI  - Randomised trial support for orthopaedic surgical procedures.
AB  - We investigated the proportion of orthopaedic procedures supported by evidence
      from randomised controlled trials comparing operative procedures to a non
      operative alternative. Orthopaedic procedures conducted in 2009, 2010 and 2011
      across three metropolitan teaching hospitals were identified, grouped and ranked
      according to frequency. Searches of the Cochrane Central Register of Controlled
      Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the
      Database of Abstracts of Reviews of Effects (DARE) were performed to identify
      RCTs evaluating the most commonly performed orthopaedic procedures. Included
      studies were categorised as "supportive" or "not supportive" of operative
      treatment. A risk of bias analysis was conducted for included studies using the
      Cochrane Collaboration's Risk of Bias tool. A total of 9,392 orthopaedic
      procedures were performed across the index period. 94.6% (8886 procedures) of the
      total volume, representing the 32 most common operative procedure categories,
      were used for this analysis. Of the 83 included RCTs, 22.9% (19/83) were
      classified as supportive of operative intervention. 36.9% (3279/8886) of the
      total volume of procedures performed were supported by at least one RCT showing
      surgery to be superior to a non-operative alternative. 19.6% (1743/8886) of the
      total volume of procedures performed were supported by at least one low risk of
      bias RCT showing surgery to be superior to a non-operative alternative. The level
      of RCT support for common orthopaedic procedures compares unfavourably with other
      fields of medicine. 

PMID- 24927116
TI  - Evaluation of the humoral immune response to human leukocyte antigens in
      Brazilian renal transplant candidates.
AB  - Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor
      for graft failure. Studies of the immunological profile related to anti-HLA
      antibodies in Brazilian renal transplant candidates are few. In this study, we
      evaluated the humoral immune response to HLA antigens in 269 renal transplant
      candidates, in Parana State, Brazil. The HLA typing was performed by the
      polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO)
      combined with Luminex technology, using an SSO-LABType commercial kit (One
      Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies
      (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA
      and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted
      of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The
      two groups differed significantly only with respect to gender. Females were the
      most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were
      positive for class I and negative for class II, 39 (21.4%) were negative for
      class I and positive for class II, and 81 (44.5%) were positive for both classes
      I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and
      DRB1*03 allele groups were the most frequent. The specificities of anti-HLA
      antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This
      study documented the profile of anti-HLA antibodies in patients with chronic
      renal failure who were on waiting lists for an organ in Parana, and found high
      sensitization to HLA antigens in the samples. 

PMID- 24927117
TI  - Characterization of the integration and modular excision of the integrative
      conjugative element PAISt in Streptomyces turgidiscabies Car8.
AB  - PAISt is a large genomic island located in the chromosome of the plant pathogen
      Streptomyces turgidiscabies Car8. The island carries clustered virulence genes,
      transfers to other Streptomyces species, and integrates by site-specific
      recombination at the 8 bp palindrome TTCATGAA. The palindrome is located at the
      3' end of the bacitracin resistance gene (bacA). We demonstrate that PAISt is
      able to excise in modules by recombination of one internal and two flanking
      palindromic direct repeats. The gene intSt located at the 3( end of PAISt encodes
      a tyrosine recombinase. Site-specific recombination activity of intSt was tested
      and confirmed by heterologous expression in Streptomyces coelicolor. Comparative
      analysis of PAISt homologues in Streptomyces scabies 87-22 and Streptomyces
      acidiscabies 84-104 indicates that these islands have been fixed by sequence
      erosion of intSt and the recombination sites. 

PMID- 24927118
TI  - Bispectral index guided titration of sevoflurane in on-pump cardiac surgery
      reduces plasma sevoflurane concentration and vasopressor requirements: a
      prospective, controlled, sequential two-arm clinical study.
AB  - BACKGROUND: Electroencephalographic-based monitoring systems such as the
      bispectral index (BIS) may reduce anaesthetic overdose rates. OBJECTIVE: We
      hypothesised that goal-directed sevoflurane administration (guided by BIS
      monitoring) could reduce the sevoflurane plasma concentration (SPC) and
      intraoperative vasopressor doses during on-pump cardiac surgery. DESIGN: A
      prospective, controlled, sequential two-arm clinical study. SETTING: German
      university medical centre with more than 2500 cardiac surgery interventions per
      year. PATIENTS: Sixty elective on-pump cardiac surgery patients. INTERVENTION: In
      group Sevo1.8% (n = 29), the sedation depth was maintained with a sustained
      inspired concentration of sevoflurane 1.8% before and during cardiopulmonary
      bypass (CPB). In group SevoBIS (n = 31), the inspired sevoflurane concentration
      was titrated to maintain a BIS target between 40 and 60. OUTCOME MEASURES: SPC
      during CPB and the intraoperative administration of noradrenaline. Additional
      analyses were performed on intraoperative awareness, postoperative blood lactate
      concentration, duration of mechanical ventilation, intensive care unit length of
      stay and kidney injury. RESULTS: Mean inspired sevoflurane concentration was 0.8%
      in group SevoBIS, representing a 57.1% reduction (P < 0.001) compared with group
      Sevo1.8%. The mean SPC was 42.3 MUg ml(-1) [95% confidence interval (CI) 40.0 to
      44.6] in group Sevo1.8% and 21.0 MUg ml(-1) (95% CI 18.8 to 23.3) in group
      SevoBIS, representing a 50.2% reduction (P < 0.001). During CPB, the mean
      cumulative dose of noradrenaline administered was 13.48 MUg kg(-1) (95% CI 10.52
      to 17.19) in group Sevo1.8% and 4.06 MUg kg(-1) (95% CI 2.67 to 5.97) in group
      SevoBIS (P < 0.001). Pearson's correlation coefficient (between the cumulative
      applied dosage of sevoflurane calculated from the area under the curve of the SPC
      over time and the administered cumulative noradrenaline dose) was 0.607 (P <
      0.001). No intraoperative awareness signs were detected. CONCLUSION: BIS-guided
      titration of sevoflurane reduces the SPC and decreases noradrenaline
      administration compared with routine care during on-pump cardiac surgery.

PMID- 24927119
TI  - Oncogene dependency and the potential of targeted RNAi-based anti-cancer therapy.
AB  - Cancers arise through the progression of multiple genetic and epigenetic defects
      that lead to deregulation of numerous signalling networks. However, the last
      decade has seen the development of the concept of 'oncogene addiction', where
      tumours appear to depend on a single oncogene for survival. RNAi has provided an
      invaluable tool in the identification of these oncogenes and oncogene-dependent
      cancers, and also presents great potential as a novel therapeutic strategy
      against them. Although RNAi therapeutics have demonstrated effective killing of
      oncogene-dependent cancers in vitro, their efficacy in vivo is severely limited
      by effective delivery systems. Several virus-based RNAi delivery strategies have
      been explored, but problems arose associated with high immunogenicity, random
      genome integration and non-specific targeting. This has directed efforts towards
      non-viral formulations, including delivery systems based on virus-like particles,
      liposomes and cationic polymers, which can circumvent some of these problems by
      immunomasking and the use of specific tumour-targeting ligands. This review
      outlines the prevalence of oncogene-dependent cancers, evaluates the potential of
      RNAi-based therapeutics and assesses the relative strengths and weaknesses of
      different approaches to targeted RNAi delivery. 

PMID- 24927120
TI  - Mechanisms of transcriptional regulation by WT1 (Wilms' tumour 1).
AB  - The WT1 (Wilms' tumour 1) gene encodes a zinc finger transcription factor and RNA
      binding protein that direct the development of several organs and tissues. WT1
      manifests both tumour suppressor and oncogenic activities, but the reasons behind
      these opposing functions are still not clear. As a transcriptional regulator, WT1
      can either activate or repress numerous target genes resulting in disparate
      biological effects such as growth, differentiation and apoptosis. The complex
      nature of WT1 is exemplified by a plethora of isoforms, post-translational
      modifications and multiple binding partners. How WT1 achieves specificity to
      regulate a large number of target genes involved in diverse physiological
      processes is the focus of the present review. We discuss the wealth of the
      growing molecular information that defines our current understanding of the
      versatility and utility of WT1 as a master regulator of organ development, a
      tumour suppressor and an oncogene. 

PMID- 24927121
TI  - Genome-wide profiling reveals a role for T-cell intracellular antigens TIA1 and
      TIAR in the control of translational specificity in HeLa cells.
AB  - TIA (T-cell intracellular antigens)-knockdown HeLa cells show an increase in
      ribosomes and translational machinery components. This increase correlates with
      specific changes in translationally up-regulated mRNAs involved in cell-cycle
      progression and DNA repair, as shown in polysomal profiling analysis. Our data
      support the hypothesis that a concerted activation of both global and selective
      translational rates leads to the transition to a more proliferative status in TIA
      knockdown HeLa cells. 

PMID- 24927122
TI  - Altered expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its
      regulatory genes in gastric cancer tissues.
AB  - Tissue hypoxia induces reprogramming of cell metabolism and may result in normal
      cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF
      1alpha), the key transcription factor, plays an important role in gastric cancer
      development and progression. This study aimed to investigate the underlying
      regulatory signaling pathway in gastric cancer using gastric cancer tissue
      specimens. The integration of gene expression profile and transcriptional
      regulatory element database (TRED) was pursued to identify HIF-1alpha <->
      NFkappaB1 -> BRCA1 -> STAT3 <- STAT1 gene pathways and their regulated genes. The
      data showed that there were 82 differentially expressed genes that could be
      regulated by these five transcription factors in gastric cancer tissues and these
      genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2,
      FCGR3A, IRF1, FAS, and TFF3) were hub molecules that are regulated at least by
      two of these five transcription factors simultaneously and were associated with
      hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed
      increasing of HIF-1alpha in mRNA and protein levels as well as TIMP1, TFF3 in
      mRNA levels in gastric cancer tissues. The data are the first study to
      demonstrate HIF-1alpha-regulated transcription factors and their corresponding
      network genes in gastric cancer. Further study with a larger sample size and more
      functional experiments is needed to confirm these data and then translate into
      clinical biomarker discovery and treatment strategy for gastric cancer. 

PMID- 24927123
TI  - Signaling mechanisms that suppress the cytostatic actions of rapamycin.
AB  - While rapamycin and the "rapalogs" Everolimus and Temsirolimus have been approved
      for clinical use in the treatment of a number of forms of cancer, they have not
      met overarching success. Some tumors are largely refractory to rapamycin
      treatment, with some even undergoing an increase in growth rates. However the
      mechanisms by which this occurs are largely unknown. The results presented here
      reveal novel cell-signaling mechanisms that may lead to this resistance. The
      absence of TGFbeta signaling results in resistance to rapamycin. Additionally, we
      observed that treatment of some cancer cell lines with rapamycin and its analogs
      not only potentiates mitogenic signaling and proliferation induced by HGF, but
      also stimulates the pro-survival kinase Akt. Together, the data show that the
      effectiveness of rapamycin treatment can be influenced by a number of factors and
      bring to light potential biomarkers for the prediction of responsiveness to
      treatment, and suggest combination therapies to optimize rapalog anticancer
      efficacy. 

PMID- 24927124
TI  - Modification of diet in renal disease (MDRD) study and CKD epidemiology
      collaboration (CKD-EPI) equations for Taiwanese adults.
AB  - BACKGROUND: Estimated glomerular filtration rate (eGFR) using the Modification of
      Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we
      developed modified eGFR equations for Taiwanese adults. METHODS: This cross
      sectional study compared the Taiwanese eGFR equations, the MDRD study, and the
      CKD-EPI equations with inulin clearance (Cin). A total of 695 adults including
      259 healthy volunteers and 436 CKD patients were recruited. Participants from the
      Kaohsiung Medical University Hospital were used as the development set (N = 556)
      to develop the Taiwanese eGFR equations, whereas participants from the National
      Taiwan University Hospital were used as the validation set (N = 139) for external
      validation. RESULTS: The Taiwanese eGFR equations were developed by using the
      extended Bland-Altman plot in the development set. The Taiwanese MDRD equation
      was 1.309 * MDRD0.912, Taiwanese CKD-EPI was 1.262*CKD-EPI0.914 and Taiwanese
      four-level CKD-EPI was 1.205 * four-level CKD-EPI0.914. In the validation set,
      the Taiwanese equations had the lowest bias, the Taiwanese equations and the
      Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the
      Japanese equations had the best precision and the highest P30 among all
      equations. However, the Taiwanese MDRD equation had higher concordance
      correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and
      the Japanese equations. Moreover, only the Taiwanese equations had no
      proportional bias among all of the equations. Finally, the Taiwanese MDRD
      equation had the best diagnostic performance in terms of ordinal logistic
      regression among all of the equations. CONCLUSION: The Taiwanese MDRD equation is
      better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and
      Taiwanese four-level CKD-EPI equations for Taiwanese adults.

PMID- 24927125
TI  - Diabetes mellitus and risk of thyroid cancer: a meta-analysis.
AB  - INTRODUCTION: Diabetes mellitus (DM) is an important risk factor for endocrine
      cancers; however, the association with thyroid cancer is not clear. We performed
      a systematic review and meta-analysis to clarify the association between thyroid
      cancer and DM. METHODS: We searched MEDLINE, PUBMED and EMBASE databases through
      July 2012, using search terms related to diabetes mellitus, cancer, and thyroid
      cancer. We conducted a meta-analysis of the risk of incidence of thyroid cancer
      from pre-existing diabetes. Of 2,123 titles initially identified, sixteen
      articles met our inclusion criteria. An additional article was identified from a
      bibliography. Totally, 14 cohort and 3 case-control studies were selected for the
      meta-analysis. The risks were estimated using random-effects model and
      sensitivity test for the studies which reported risk estimates and used different
      definition of DM. RESULTS: Compared with individuals without DM, the patients
      with DM were at 1.34-fold higher risk for thyroid cancer (95% CI 1.11-1.63).
      However, there was heterogeneity in the results (p<0.0001). Sensitivity tests and
      studies judged to be high quality did not show heterogeneity and DM was
      associated with higher risk for thyroid cancer in these sub-analyses (both of RRs
      = 1.18, 95% CIs 1.08-1.28). DM was associated with a 1.38-fold increased risk of
      thyroid cancer in women (95% CI 1.13-1.67) after sensitivity test. Risk of
      thyroid cancer in men did not remain significant (RR 1.11, 95% CI 0.80-1.53).
      CONCLUSIONS: Compared with their non-diabetic counterparts, women with pre
      existing DM have an increased risk of thyroid cancer.

PMID- 24927126
TI  - Development of a highly sensitive glycan microarray for quantifying AFP-L3 for
      early prediction of hepatitis B virus-related hepatocellular carcinoma.
AB  - The alpha-fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant
      cells and incorporates a fucosylated oligosaccharide, has been investigated as a
      diagnostic and prognostic marker for hepatocellular carcinoma (HCC).
      Quantification of AFP-L3 by conventional enzyme-linked immunosorbent assay
      (ELISA) has not always produced reliable results for serum samples with low AFP,
      and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and
      highly sensitive glycan microarray assay. Sera from 9 patients with chronic
      hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested
      for AFP-L3 level using the glycan microarray. Additionally, we compared receiver
      operator characteristic curves for the ELISA and glycan microarray methods for
      determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was
      calculated for 8 HCC patients who underwent transarterial embolization therapy
      pre- or post-treatment with AFP-L3. Glycan microarrays showed that the AFP-L3
      ratio of HBV-related HCC patients was significantly higher than that measured for
      chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC
      samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under
      the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was
      strongly associated with HCC progression. Following one month of transarterial
      embolization therapy, the relative mean AFP-L3% decreased significantly. In
      addition, we compared Fut8 gene expression between paired tumor and non-tumor
      tissues from 24 patients with HBV-related HCC. The Fut8 mRNA expression was
      significantly increased in tumorous tissues in these patients than that in non
      tumor tissue controls. Higher expression of Fut8 mRNA in tumorous tissues in
      these patients was associated with poor differentiation than well and moderate
      differentiation. Our results describe a new glycan microarray for the sensitive
      and rapid quantification of fucosylated AFP; this method is potentially
      applicable to screening changes in AFP-L3 level for assessment of HCC
      progression. 

PMID- 24927127
TI  - Nature and pattern of cricket injuries: the Asian Cricket Council Under-19, Elite
      Cup, 2013.
AB  - Cricket has over the years gained much popularity in Asia, thus the number of
      cricket players has also grown in tandem. However, cricket players are not as
      fortunate as other athletes as they do not always have a standard cricket
      infrastructure to practice; therefore, the injury prevalence is expected to be
      high. Unfortunately, very few studies have been conducted to investigate the
      nature and pattern of cricket injuries prevalent to cricketers in this region.
      Therefore, a prospective cohort injury surveillance study was conducted during
      the Asian Cricket Council (ACC) Under-19 Elite Cup held in June 2013 in order to
      gather more data on the type of injuries sustained by cricket players. Overall,
      31 injuries occurred to 28 players throughout the tournament, of which 7 injuries
      happened during practice sessions. The overall injury incidence rate (IIR) was
      292.0 per 10,000 player hours (95% CI 176.9-407.1) and 10.4 per 10,000 balls
      faced and 2.6 per 1000 overs bowled delivered during batting and bowling,
      respectively. Injuries to the lower limb (IIR: 146; 95% CI 1.8-98.2) were the
      most frequent, followed by injuries to the upper limb (97.3;95% CI 30.2-164.5)
      and to the trunk and back (IIR: 36.5;95% CI 0.0-77.7). Sprain/strains (IIR
      109.5;95% CI 38.4-180.7) to muscle/tendon and joint/ligament were the most
      commonly reported nature of injury. This is the first study investigating injury
      incidence among the players of the ACC. It provides an overview of injuries
      sustained by elite players' under-19 years of age from 10 Asian countries. The
      overall IIR is similar to earlier studies conducted in well-established cricket
      playing nations.

PMID- 24927129
TI  - Selection of optimal auxiliary soil nutrient variables for Cokriging
      interpolation.
AB  - In order to explore the selection of the best auxiliary variables (BAVs) when
      using the Cokriging method for soil attribute interpolation, this paper
      investigated the selection of BAVs from terrain parameters, soil trace elements,
      and soil nutrient attributes when applying Cokriging interpolation to soil
      nutrients (organic matter, total N, available P, and available K). In total, 670
      soil samples were collected in Fuyang, and the nutrient and trace element
      attributes of the soil samples were determined. Based on the spatial
      autocorrelation of soil attributes, the Digital Elevation Model (DEM) data for
      Fuyang was combined to explore the coordinate relationship among terrain
      parameters, trace elements, and soil nutrient attributes. Variables with a high
      correlation to soil nutrient attributes were selected as BAVs for Cokriging
      interpolation of soil nutrients, and variables with poor correlation were
      selected as poor auxiliary variables (PAVs). The results of Cokriging
      interpolations using BAVs and PAVs were then compared. The results indicated that
      Cokriging interpolation with BAVs yielded more accurate results than Cokriging
      interpolation with PAVs (the mean absolute error of BAV interpolation results for
      organic matter, total N, available P, and available K were 0.020, 0.002, 7.616,
      and 12.4702, respectively, and the mean absolute error of PAV interpolation
      results were 0.052, 0.037, 15.619, and 0.037, respectively). The results
      indicated that Cokriging interpolation with BAVs can significantly improve the
      accuracy of Cokriging interpolation for soil nutrient attributes. This study
      provides meaningful guidance and reference for the selection of auxiliary
      parameters for the application of Cokriging interpolation to soil nutrient
      attributes. 

PMID- 24927128
TI  - Pharmacological preconditioning with vitamin C attenuates intestinal injury via
      the induction of heme oxygenase-1 after hemorrhagic shock in rats.
AB  - Pre-induction of heme oxygenase (HO)-1, which is regarded as an effective method
      of "organ preconditioning", exerts beneficial effects during hemorrhagic shock
      (HS). However, the available HO-1 inducers exhibit disadvantages such as toxicity
      or complex technical requirements. Therefore, a safe and convenient HO-1 inducer
      would be promising and could be exploited in the treatment of foreseeable
      hemorrhaging, such as prior to major surgery. Here we investigated the effect of
      vitamin C (VitC), a common antioxidant, on intestinal HO-1 expression and
      examined whether VitC pretreatment prevented HS related intestinal tissue
      injuries after HO-1 induction. First, we conducted an in vitro study and found
      that HO-1 expression in rat intestinal epithelial cells (IEC-6) was induced by
      non-toxic VitC in a time and concentration dependent manner, and the mechanism
      was related to the activation of extracellular signal-regulated kinase 1/2
      (ERK1/2). Next, we conducted an in vivo study and found that VitC induced
      intestinal HO-1 protein expression (mainly observed in the intestinal epithelial
      cells) and HO-1 activity in normal SD rats, and that these HO-1 levels were
      further enhanced by VitC in a rat model of HS. The HS related intestinal
      injuries, including histological damage, pro-inflammatory cytokine levels (tumor
      necrosis factor and interleukin-6), neutrophil infiltration and apoptosis
      decreased after VitC pretreatment, and this alleviating of organ injuries was
      abrogated after the inhibition of HO-1 activity by zinc protoporphyrin-IX. It was
      of note that VitC did little histological damage to the intestine of the sham
      rats. These data suggested that VitC might be applied as a safe inducer of
      intestinal HO-1 and that VitC pretreatment attenuated HS related intestinal
      injuries via the induction of HO-1. 

PMID- 24927130
TI  - Daily changes in temperature, not the circadian clock, regulate growth rate in
      Brachypodium distachyon.
AB  - Plant growth is commonly regulated by external cues such as light, temperature,
      water availability, and internal cues generated by the circadian clock. Changes
      in the rate of growth within the course of a day have been observed in the
      leaves, stems, and roots of numerous species. However, the relative impact of the
      circadian clock on the growth of grasses has not been thoroughly characterized.
      We examined the influence of diurnal temperature and light changes, and that of
      the circadian clock on leaf length growth patterns in Brachypodium distachyon
      using high-resolution time-lapse imaging. Pronounced changes in growth rate were
      observed under combined photocyles and thermocycles or with thermocycles alone. A
      considerably more rapid growth rate was observed at 28 degrees C than 12 degrees
      C, irrespective of the presence or absence of light. In spite of clear circadian
      clock regulated gene expression, plants exhibited no change in growth rate under
      conditions of constant light and temperature, and little or no effect under
      photocycles alone. Therefore, temperature appears to be the primary cue
      influencing observed oscillations in growth rate and not the circadian clock or
      photoreceptor activity. Furthermore, the size of the leaf meristem and final cell
      length did not change in response to changes in temperature. Therefore, the
      nearly five-fold difference in growth rate observed across thermocycles can be
      attributed to proportionate changes in the rate of cell division and expansion. A
      better understanding of the growth cues in B. distachyon will further our ability
      to model metabolism and biomass accumulation in grasses. 

PMID- 24927131
TI  - Alkynyl crown ethers as a scaffold for hyperconjugative assistance in
      noncatalyzed azide-alkyne click reactions: ion sensing through enhanced
      transition-state stabilization.
AB  - Our recent work has provided an alternative strategy for acceleration of
      azide/alkyne cycloadditions via selective transition state (TS) stabilization.
      Optimization of hyperconjugative assistance, provided by the antiperiplanar
      arrangement of propargylic sigma-acceptors relative to the forming bonds, is
      predicted to relieve strain in cyclooctynes while providing large acceleration to
      the cycloaddition. The present work investigates this strategy in alkynyl crown
      ethers, where propargylic C-O bonds contained within the macrocycle are
      constrained close to proper alignment for hyperconjugative assistance.
      Preorganization of sigma-acceptors into the optimal arrangement for
      hyperconjugative interactions may alleviate a portion of the entropic penalty for
      reaching the TS. Optimal alignment can be reinforced, and transition-state
      stabilization can be further amplified by binding positively charged ions to the
      crown ether core, highlighting the potential for applications in ion sensing. 

PMID- 24927132
TI  - Beware of multiple traumas in PTSD assessment: the role of reactivation mechanism
      in intrusive and hyper-arousal symptoms.
AB  - OBJECTIVES: Post-traumatic stress disorder (PTSD) is a major public health
      problem defined by three symptom clusters: intrusion thoughts, avoidance
      mechanisms and hyper-arousal. Several authors have emphasized, that some or all
      of these symptoms related to a past traumatic experience could be reactivated,
      even after long asymptomatic periods. This study investigates the role of an
      additional trauma in the reactivation of a childhood trauma among a group of
      former hidden children (n = 65), the Jewish youths who spent World War II in
      various hideaway shelters in Nazi-occupied Europe. They were compared with a
      control group. METHOD: The presence or absence of an additional trauma in
      adulthood was assessed and PTSD symptoms were measured by using the Impact of
      Event Scale-Revised. RESULTS: An additional trauma reactivates PTSD symptoms of
      intrusion thoughts and, marginally, symptoms of hyper-arousal. At the opposite,
      symptoms of avoidance were not reactivated. CONCLUSION: Our results confirm the
      role of an additional trauma in the reactivation of traumatic memories, related
      to an earlier trauma, in later life. Clinical and theoretical implications are
      discussed and perspectives are proposed.

PMID- 24927133
TI  - A sensitive luminescent assay for the histone methyltransferase NSD1 and other
      SAM-dependent enzymes.
AB  - A major focus of our pediatric cancer research is the discovery of chemical
      probes to further our understanding of the biology of leukemia harboring fusion
      proteins arising from chromosomal rearrangements, and to develop novel
      specifically targeted therapies. The NUP98-NSD1 fusion protein occurs in a highly
      aggressive subtype of acute myeloid leukemia after rearrangement of the genes
      NUP98 and NSD1. The methyltransferase activity of NSD1 is retained in the fusion,
      and it gives rise to abnormally high levels of methylation at lysine 36 on
      histone 3, enforcing oncogene activation. Therefore, inhibition of the
      methyltransferase activity of NUP98-NSD1 may be considered a viable therapeutic
      strategy. Here, we report the development and validation of a highly sensitive
      and robust luminescence-based assay for NSD1 and other methyltransferases that
      use S-adenosylmethionine (SAM) as a methyl donor. The assay quantifies S
      adenosylhomocysteine (SAH), which is produced during methyl transfer from SAM.
      SAH is converted enzymatically to adenosine monophosphate (AMP); in the process,
      adenosine triphosphate (ATP) is consumed and the amount of ATP remaining is
      measured using a luminescent assay kit. The assay was validated by pilot high
      throughput screening (HTS), dose-response confirmation of hits, and elimination
      of artifacts through counterscreening against SAH detection in the absence of
      NSD1. The known methyltransferase inhibitor suramin was identified, and profiled
      for selectivity against the histone methyltransferases EZH2, SETD7, and PRMT1.
      HTS using the luminescent NSD1 assay described here has the potential to deliver
      selective NSD1 inhibitors that may serve as leads in the development of targeted
      therapies for NUP98-NSD1-driven leukemias.

PMID- 24927135
TI  - Brominated flame retardants in matched serum samples from Swedish first-time
      mothers and their toddlers.
AB  - Tri-decabrominated diphenyl ethers and 21 other flame retardants were determined
      in matched serum samples from 24 Swedish mothers (Uppsala county) and their
      toddlers (11-15 months of age). The median concentrations of individual
      polybrominated diphenyl ethers (PBDEs) ranged from 0.036 to 0.95 ng/g lipid in
      mothers and from 0.057 to 1.5 ng/g lipid in toddlers. BDE-209 was detected in all
      but one sample. BDE-153 was the predominant congener in the mothers while in
      toddlers, BDE-209 was found in the highest concentrations. The levels of BDE-47, 
      100, -207, -208, and -209 in toddlers were significantly higher (p < 0.05) than
      those in their mothers. Dechlorane Plus (anti- and syn-) and alpha- and beta
      tetrabromoethylcyclohexane were detected in a few (2-4) serum samples from both
      mothers and toddlers. This study also reports concentrations of alpha-HBCD and
      eight emerging brominated flame retardants (EBFRs) in the standard reference
      material serum (SRM 1958, NIST). Lack of correlations between the matched serum
      samples indicate different exposure routes for octa-decaBDEs in mothers versus
      toddlers. Congener-to-congener correlations within the mother or toddler cohorts
      suggest diet as an important exposure pathway for tetra-nonaBDEs for mothers,
      breastfeeding as a predominant exposure pathway for tetra-hexaBDEs, and dust for
      octa-decaBDEs for toddlers. 

PMID- 24927134
TI  - Evaluation of cytotoxicity and DNA damage response with analysis of intracellular
      ATM signaling pathways.
AB  - Maintenance of genome integrity by preventing and overcoming DNA damage is
      critical for cell survival. Deficiency or aberrancy in the DNA damage response,
      for example, through ataxia telangiectasia mutated (ATM) signaling, lead to
      pathophysiological perturbations in organs throughout the body. Therefore,
      control of DNA damage is of major interest for development of therapeutic agents.
      Such efforts will greatly benefit from convenient and simple diagnostic and/or
      drug development tools to demonstrate whether ATM and related genes have been
      activated and to then determine whether these have been returned to normal levels
      of activity because pathway members sense and also repair DNA damage. To overcome
      difficulties in analyzing differences in multitudinous ATM pathway members
      following DNA damage, we measured ATM promoter activity with a fluorescent td
      Tomato reporter gene to interrogate the global effects of ATM signaling pathways.
      In cultured HuH-7 cell line derived from human hepatocellular carcinoma, cis
      platinum, acetaminophen, or hydrogen peroxide caused DNA strand breaks and ATM
      pathway activation as shown by gammaH2AX expression, which in turn, led to rapid
      and sustained increases in ATM promoter activity. This assay of ATM promoter
      activity identified biological agents capable of controlling cellular DNA damage
      in toxin-treated HuH-7 cells and in mice after onset of drug-induced acute liver
      failure. Therefore, the proposed assay of ATM promoter activity in HuH-7 cells
      was appropriately informative for treating DNA damage. High-throughput screens
      using ATM promoter activation will be helpful for therapeutic development in DNA
      damage-associated abnormal ATM signaling in various cell types and organs.

PMID- 24927137
TI  - Objectively determined refraction improves peripheral vision.
AB  - PURPOSE: The purpose of this study was twofold: to verify a fast, clinically
      applicable method for determining off-axis refraction and to assess the impact of
      objectively obtained off-axis refractive correction on peripheral low-contrast
      visual acuity. METHODS: We measured peripheral low-contrast resolution acuity
      with Gabor patches both with and without off-axis correction at 20 degrees in the
      nasal visual field of 10 emmetropic subjects; the correction was obtained using a
      commercial open-field Hartmann-Shack wavefront sensor, the COAS-HD VR
      aberrometer. Off-axis refractive errors were calculated for a 5-mm circular pupil
      inscribed within the elliptical wavefront by COAS using the instruments' inbuilt
      "Seidel sphere" method. RESULTS: Most of the subjects had simple myopic
      astigmatism, at 20 degrees in the nasal visual field ranging from -1.00 to -2.00
      DC, with axis orientations generally near 90 degrees. The mean uncorrected and
      corrected low-contrast resolution acuities for all subjects were 0.92 and 0.86
      logMAR, respectively (an improvement of 0.06 logMAR). For subjects with a scalar
      power refractive error of 1.00 diopters or more, the average improvement was 0.1
      logMAR. The observed changes in low-contrast resolution acuity were strongly
      correlated with off-axis astigmatism (Pearson r = 0.95; p < 0.0001), the J180
      cross-cylinder component (Pearson r = 0.82; p = 0.0034), and power scalar
      (Pearson r = -0.75; p = 0.0126). CONCLUSIONS: The results suggest that there are
      definite benefits in correcting even moderate amounts of off-axis refractive
      errors; in this study, as little as -1.50 DC of off-axis astigmatism gave
      improvements of up to a line in visual acuity. It may be even more pertinent for
      people who rely on optimal peripheral visual function, specifically those with
      central visual field loss; the use of open-field aberrometers could be clinically
      useful in rapidly determining off-axis refractive errors specifically for this
      patient group who are generally more challenging to refract.

PMID- 24927136
TI  - The bigaussian nature of ocular biometry.
AB  - PURPOSE: To study how the leptokurtic shape of the refractive distribution can be
      derived from ocular biometry by means of a multivariate Gaussian model. METHODS:
      Autorefraction and optical biometry data (Scheimpflug and partial coherence
      interferometry) were obtained for 1136 right eyes of healthy white subjects
      recruited by various European ophthalmological centers participating in Project
      Gullstrand. These biometric data were fitted with linear combinations of
      multivariate Gaussians to create a Monte Carlo simulation of the biometry, from
      which the corresponding refraction was calculated. These simulated data were then
      compared with the original data by histogram analysis. RESULTS: The distribution
      of the ocular refraction more closely resembled a bigaussian than a single
      Gaussian function (F test, p < 0.001). This also applied to the axial length,
      which caused the combined biometry data to be better represented by a linear
      combination of two multivariate Gaussians rather than by a single one (F test, p
      < 0.001). Corneal curvature, anterior chamber depth, and lens power, on the other
      hand, displayed a normal distribution. All distributions were found to gradually
      change with age. The statistical descriptors of these two subgroups were compared
      and found to differ significantly in average and SD for the refraction, axial
      length, and anterior chamber depth. All distributions were also found to change
      significantly with age. CONCLUSIONS: The bigaussian model provides a more
      accurate description of the data from the original refractive distribution and
      suggests that the general population may be composed of two separate subgroups
      with different biometric properties.

PMID- 24927138
TI  - Lack of association between LUM rs3759223 polymorphism and high myopia.
AB  - PURPOSE: Previous evidence has indicated that the lumican (LUM) gene is a
      candidate susceptibility gene of high myopia; however, the association between
      LUM promoter regions rs3759223 polymorphism and high myopia remains controversial
      and ambiguous. This study performed a meta-analysis to clarify the association
      between the rs3759223 polymorphism and high myopia risk. METHODS: Eligible
      studies were identified by comprehensive search of PubMed, EMBASE, Web of
      Science, and Chinese Biomedical Literature database. The crude odds ratios (ORs)
      and their corresponding 95% confidence intervals (CIs) were used to estimate the
      association between the rs3759223 polymorphism and high myopia susceptibility.
      Meta-regression and subgroup analyses were performed to identify the source of
      heterogeneity. RESULTS: Finally, six studies including 1238 cases and 1059
      healthy controls were included. Meta-analyses showed no association between
      rs3759223 polymorphism and high myopia susceptibility in all genetic models (CC
      vs. TT, OR = 1.089; 95% CI, 0.690 to 1.718; CT vs. TT, OR = 0.865; 95% CI, 0.646
      to 1.157; CC + CT vs. TT, OR = 1.202; 95% CI, 0.730 to 1.980; CC vs. CT + TT, OR
      = 0.914; 95% CI, 0.771 to 1.083) and no significance in subgroup analyses
      according to the definition of high myopia (based on more myopic than -6.00
      diopters vs. not based on more myopic than -6.00 diopters). Publication bias was
      not evident in this study. CONCLUSIONS: This meta-analysis has suggested that
      there is a lack of association of the rs3759223 polymorphism with high myopia
      risk. However, further large and well-designed studies with the consideration of
      LUM gene locus interactions and gene-gene and gene-environment interactions are
      still required to further evaluate high myopia risk.

PMID- 24927139
TI  - Acquired pseudoduplication of the optic disc in pathologic myopia.
AB  - PURPOSE: To elucidate the mechanism of acquired pseudoduplication of the optic
      disc and its association with pathologic myopia. METHODS: The prevalence of
      pseudoduplication of the optic disc was estimated by reviewing 128 consecutive
      patients diagnosed as having pathologic myopia between January 2010 and December
      2012. The pseudodisc was investigated at the scleral level using enhanced depth
      imaging spectral-domain optical coherence tomography to elucidate pathologic
      changes. Fluorescein angiography or indocyanine green angiography was performed
      to identify the vessel origin. RESULTS: Among 128 patients with pathologic
      myopia, 3 patients (2.3%) showed pseudoduplication of the optic disc. Enhanced
      depth imaging optical coherence tomography showed chorioretinal atrophy and focal
      scleral excavation in the area showing the pseudodisc. The round scleral
      excavation gave the underlying visible peribulbar tissue a pinkish appearance,
      which could be mistaken as the optic disc. Fluorescein angiography or indocyanine
      green angiography showed that the vessel within the pseudodisc was the short
      posterior ciliary artery. CONCLUSIONS: Although not a common presentation,
      scleral excavation associated with pathologic myopia accompanied by a ciliary
      artery penetrating the excavation's center could make a lesion mimicking
      pseudoduplication of the optic disc.

PMID- 24927140
TI  - Patient tobacco use in optometric practice: a Canada-wide study.
AB  - PURPOSE: A national census survey of optometrists in Canada measured knowledge of
      ocular diseases associated with smoking cigarettes and current practice behaviors
      related to addressing tobacco use with patients, including prevention and
      cessation. Optometrists were also asked to identify tools to assist addressing
      tobacco use with patients. METHODS: An online bilingual (English/French) survey
      was developed and an e-mail with a link to the survey was sent to all 4528
      optometrists registered in Canada. No participation incentives were provided.
      Frequency data were tabulated for survey items. Logistic regression models were
      fit to understand respondent characteristics associated with discussing tobacco
      use prevention and cessation with patients. RESULTS: The response rate was 19%
      (850 responses). Almost all respondents (98%) believed that smoking cigarettes
      was a risk factor for developing age-related macular degeneration; approximately
      half (55%) assessed the smoking status of patients during their initial visit; 7%
      reported that they discussed the benefits of tobacco use prevention with patients
      younger than 19 years; and 33% reported that they always or regularly assess
      their patients' interest in quitting smoking. Respondents who completed the
      survey in English were more likely (odds ratio, 2.4; 95% confidence interval,
      1.01 to 5.65) to deliver prevention messaging, compared with respondents who
      completed the survey in French. Male respondents were less likely to assess
      patients' interest in quitting (odds ratio, 0.7; 95% confidence interval, 0.50 to
      0.97) than female respondents. Most respondents (90%) were interested in a
      continuing education program about the impact of smoking on vision and eye health
      as well as strategies for discussing tobacco cessation and prevention.
      CONCLUSIONS: Optometrists are aware of the impact of smoking on ocular health;
      however, most respondents do not systematically engage in tobacco use prevention
      and cessation practices. Providing optometrists with tools, including continuing
      education, may help support patient conversations about the risks of tobacco use
      and improve public health.

PMID- 24927141
TI  - Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma.
AB  - PURPOSE: To identify the spectrum of somatic mutations in an Asian Indian patient
      with uveal melanoma (UM) without metastasis using exome sequencing. CASE REPORT:
      A 49-year-old man from India was diagnosed as having cilio-choroidal (uveal)
      melanoma (UM), without metastasis, in his right eye with the help of magnetic
      resonance imaging. This was later confirmed by histopathological evaluation. Two
      individuals from India with non-neoplastic blind eyes were recruited as controls.
      The affected eyes from the UM patient and the two control individuals were
      enucleated, and uveal tissues were collected. DNA was extracted from uveal
      tissue, and the matched blood sample from each of the three individuals was
      followed by exome sequencing. Statistical and bioinformatic analyses were done to
      identify somatic mutations and their putative associations with UM. Thirty-one
      somatic mutations (25 amino acid altering) in protein-coding (exonic) regions
      were detected in the UM patient. Of the amino acid-altering somatic mutations, 16
      mutations were predicted to be candidate mutations relevant to UM. Somatic
      mutations, putatively causal for UM, were identified in GNAQ, SF3B1, and SOX10.
      CONCLUSIONS: Somatic mutations in GNAQ and SF3B1 genes were probable drivers of
      UM in the Indian patient; these were also reported earlier in some White
      patients. In addition, a frameshift deletion of 20 base pairs has been identified
      in SOX10 in the UM patient. Somatic mutations in SOX10, a transcription factor,
      which acts upstream of microphthalmia-associated transcription factor and
      synergizes with microphthalmia-associated transcription factor, was identified in
      some melanoma cell lines. The transcription factor SOX10 was found to have an
      essential role in melanocyte development and pigmentation. Our finding of the
      frameshift deletion (p.H387fs) in exon 4 of SOX10 in UM provides an important
      insight and complements earlier findings of mutations in GNAQ and SF3B1 on the
      genomic basis of UM.

PMID- 24927142
TI  - Utility of theoretical Hirschberg ratio for gaze position calibration.
AB  - PURPOSE: Gaze position is calibrated in first Purkinje image-based eye trackers
      using the population-average Hirschberg ratio (HR) that is prone to inaccuracies
      or using the individual's HR that is cumbersome to obtain empirically. This study
      investigated (1) the agreement between HR calculated theoretically from the
      individual's corneal curvature and anterior chamber (AC) depth and those obtained
      empirically and (2) the contribution of corneal curvature and AC depth in the
      intersubject variance of the two HRs. METHODS: Twenty-four subjects (mean +/- SD
      age, 23.6 +/- 3.5 years) fixated monocularly on a light-emitting diode array
      spanning +/-24 degrees of horizontal or vertical gaze angle, in 4-degree steps,
      at 95 cm viewing distance. Empirical HR was determined using a custom-designed
      infrared eye tracker as the magnitude of separation between Purkinje image
      position and entrance pupil center per unit change in angular eccentricity.
      Theoretical HR was calculated from the subject's corneal curvature and AC depth
      using the model of Brodie (1987). RESULTS: Empirical and theoretical HRs for
      horizontal and vertical gaze directions were well correlated (r >= 0.83) and not
      significantly different from each other (p >= 0.23; mean difference [+/-95%
      limits of agreement], -0.35 [0.85 to -1.55] degrees/mm for horizontal HR and 
      0.16 [1.01 to -1.33] degrees/mm for vertical HR). Corneal curvature and AC depth
      together accounted for greater than or equal to 80% and greater than or equal to
      91% of intersubject variance in empirical and theoretical HR, respectively (p <
      0.001). Hirschberg ratios changed at -2.3 to -2.8 degrees/mm per millimeter
      change in corneal curvature and at 2.0 to 2.4 degrees/mm per millimeter change in
      AC depth. CONCLUSIONS: Theoretical HR calculated from the individual's corneal
      curvature and AC depth can be used in lieu of the empirical HR for gaze position
      calibration to within approximately 2 degrees/mm of accuracy. Gaze position
      accuracy significantly improves by using the theoretical HR, relative to the
      population-average HR. Corneal curvature and AC depth combined explain the
      majority of intersubject variability in HR.

PMID- 24927143
TI  - Changes in macular function after ozurdex for retinal vein occlusion.
AB  - PURPOSE: To investigate changes in macular function after intravitreal
      dexamethasone implant (Ozurdex) for macular edema (ME) secondary to retinal vein
      occlusion (RVO). METHODS: Nineteen treatment-naive patients with RVO-related ME
      were treated with intravitreal Ozurdex and followed up to 6 months to evaluate
      functional outcomes, by means of best-corrected visual acuity, microperimetry,
      and multifocal electroretinography, and their correlations with morphological
      parameters by enhanced depth imaging optical coherence tomography. RESULTS:
      Nineteen eyes of 19 patients were included for analysis. At 1 month, mean best
      corrected visual acuity, retinal sensitivity, and central macular thickness (CMT)
      improved from 0.50 +/- 0.34 LogMAR, 10.51 +/- 4.31 dB, and 762 +/- 259 MUm
      (baseline) to 0.38 +/- 0.34 LogMAR (p = 0.043), 12.28 +/- 5.06 dB (p = 0.025),
      and 385 +/- 191 MUm (p = 0.001), respectively. At 3 months, improvement of mean
      retinal sensitivity and CMT was still significant (11.62 +/- 5.05 dB [p = 0.047]
      and 518 +/- 251 MUm [p = 0.006]). Multifocal electroretinography measurements
      also showed (nonsignificant) improvement. No significant changes in choroidal
      thickness were recorded. Improvements recorded during the first 3 months were no
      longer significant from month 4. At each time point, we found a negative
      significant correlation between CMT and retinal sensitivity. Interestingly, 7
      eyes did not undergo retreatment of less than 6 months; these eyes showed a
      significantly better baseline retinal sensitivity than eyes requiring retreatment
      of less than 6 months (12.27 +/- 3.52 dB vs. 9.48 +/- 4.53 dB [p = 0.038]).
      CONCLUSIONS: In eyes with ME secondary to RVO, intravitreal dexamethasone implant
      provides functional benefits as soon as 1 month after treatment. In most cases,
      the optimum retreatment interval is less than 6 months from first intravitreal
      Ozurdex. Microperimetry is a very useful tool to characterize macular function.
      Baseline macular sensitivity may predict the need for early (<6 months)
      retreatment.

PMID- 24927144
TI  - Mitigating the effects of Xuebijing injection on hematopoietic cell injury
      induced by total body irradiation with gamma rays by decreasing reactive oxygen
      species levels.
AB  - Hematopoietic injury is the most common side effect of radiotherapy. However, the
      methods available for the mitigating of radiation injury remain limited.
      Xuebijing injection (XBJ) is a traditional Chinese medicine used to treat sepsis
      in the clinic. In this study, we investigated the effects of XBJ on the survival
      rate in mice with hematopoietic injury induced by gamma ray ionizing radiation
      (IR). Mice were intraperitoneally injected with XBJ daily for seven days after
      total body irradiation (TBI). Our results showed that XBJ (0.4 mL/kg)
      significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This
      effect may be attributable to improved preservation of white blood cells (WBCs)
      and hematopoietic cells, given that bone marrow (BM) cells from XBJ-treated mice
      produced more granulocyte-macrophage colony forming units (CFU-GM) than that in
      the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species
      (ROS) by increasing glutathione (GSH) and superoxide dismutase (SOD) levels in
      serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In
      conclusion, these findings suggest that XBJ enhances the survival rate of
      irradiated mice and attenuates the effects of radiation on hematopoietic injury
      by decreasing ROS production in BM cells, indicating that XBJ may be a promising
      therapeutic candidate for reducing hematopoietic radiation injury. 

PMID- 24927145
TI  - Biochemical properties of a new cold-active mono- and diacylglycerol lipase from
      marine member Janibacter sp. strain HTCC2649.
AB  - Mono- and di-acylglycerol lipase has been applied to industrial usage in oil
      modification for its special substrate selectivity. Until now, the reported mono-
      and di-acylglycerol lipases from microorganism are limited, and there is no
      report on the mono- and di-acylglycerol lipase from bacteria. A predicted lipase
      (named MAJ1) from marine Janibacter sp. strain HTCC2649 was purified and
      biochemical characterized. MAJ1 was clustered in the family I.7 of
      esterase/lipase. The optimum activity of the purified MAJ1 occurred at pH 7.0 and
      30  degrees C. The enzyme retained 50% of the optimum activity at 5  degrees C,
      indicating that MAJ1 is a cold-active lipase. The enzyme activity was stable in
      the presence of various metal ions, and inhibited in EDTA. MAJ1 was resistant to
      detergents. MAJ1 preferentially hydrolyzed mono- and di-acylglycerols, but did
      not show activity to triacylglycerols of camellia oil substrates. Further, MAJ1
      is low homologous to that of the reported fungal diacylglycerol lipases,
      including Malassezia globosa lipase 1 (SMG1), Penicillium camembertii lipase U
      150 (PCL), and Aspergillus oryzae lipase (AOL). Thus, we identified a novel cold
      active bacterial lipase with a sn-1/3 preference towards mono- and di
      acylglycerides for the first time. Moreover, it has the potential, in oil
      modification, for special substrate selectivity. 

PMID- 24927146
TI  - The role of circulating microRNA-126 (miR-126): a novel biomarker for screening
      prediabetes and newly diagnosed type 2 diabetes mellitus.
AB  - Recent studies suggested an association of endothelial microRNA-126 (miR-126)
      with type 2 diabetes mellitus (T2DM). In the current study, we examined whether
      circulating miR-126 is associated with T2DM and pre-diabetic syndrome. The study
      included 82 subjects with impaired glucose tolerance (IGT), 75 subjects with
      impaired fasting glucose (IFG), 160 patients with newly diagnosed T2DM, and 138
      healthy individuals. Quantitative polymerase chain reaction (qPCR) was used to
      examine serum miR-126. Serum miR-126 was significantly lower in IGT/IFG subjects
      and T2DM patients than in healthy controls (p<0.05). After six months of
      treatment (diet control and exercise in IGT/IFG subjects, insulin plus diet
      control and exercise in T2DM patients), serum miR-126 increased significantly
      (p<0.05). An analysis based on serum miR-126 in the sample revealed a
      significantly higher odds ratio (OR) for the subjects with the lowest 1/3 of
      serum miR-126 for T2DM (OR: 3.500, 95% confidence interval: 1.901-6.445, p<0.05)
      than subjects within the highest 1/3 of serum miR-126. Such an association was
      still apparent after adjusting for other major risk factors. The area under the
      curve (AUC) for the receiver-operating characteristic (ROC) analysis was 0.792
      (95% confidence interval: 0.707-0.877, p<0.001). These results encourage the use
      of serum miR-126 as a biomarker for pre-diabetes and diabetes mellitus, as well
      as therapeutic response.

PMID- 24927148
TI  - Genistein inhibits osteoclastic differentiation of RAW 264.7 cells via regulation
      of ROS production and scavenging.
AB  - Genistein, a phytoestrogen, has been demonstrated to have a bone-sparing and
      antiresorptive effect. Genistein can inhibit the osteoclast formation of receptor
      activator of nuclear factor-kappaB ligand (RANKL)-induced RAW 264.7 cells by
      preventing the translocation of nuclear factor-kappaB (NF-kappaB), a redox
      sensitive factor, to the nucleus. Therefore, the suppressive effect of genistein
      on the reactive oxygen species (ROS) level during osteoclast differentiation and
      the mechanism associated with the control of ROS levels by genistein were
      investigated. The cellular antioxidant capacity and inhibitory effect of
      genistein were confirmed. The translation and activation of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase 1 (Nox1), as well as the disruption of the
      mitochondrial electron transport chain system were obviously suppressed by
      genistein in a dose-dependent manner. The induction of phase II antioxidant
      enzymes, such as superoxide dismutase 1 (SOD1) and heme oxygenase-1 (HO-1), was
      enhanced by genistein. In addition, the translational induction of nuclear factor
      erythroid 2-related factor 2 (Nrf2) was notably increased by genistein. These
      results provide that the inhibitory effects of genistein on RANKL-stimulated
      osteoclast differentiation is likely to be attributed to the control of ROS
      generation through suppressing the translation and activation of Nox1 and the
      disruption of the mitochondrial electron transport chain system, as well as ROS
      scavenging through the Nrf2-mediated induction of phase II antioxidant enzymes,
      such as SOD1 and HO-1. 

PMID- 24927150
TI  - Marine natural products-inspired phenylmethylene hydantoins with potent in vitro
      and in vivo antitumor activities via suppression of Brk and FAK signaling.
AB  - Breast and prostate cancers are among the most common cancers worldwide with
      devastating statistics for the metastatic, chemotherapy- and radiotherapy
      resistant phenotypes. Novel therapies interfering with new and/or multiple
      pathways involved in the pathology of cancer are urgently needed. Preliminary
      results showed that the marine natural product Z-4-hydroxyphenylmethylene
      hydantoin (PMH, ) and its 4-ethylthio-analog (SEth, ) promoted tight junction
      formation and showed anti-invasive and anti-migratory activities in vitro against
      metastatic prostate cancer cells and inhibited tumor growth and micrometastases
      in distant organs in orthotopic and transgenic mice models. This study focuses on
      the design and synthesis of second-generation PMHs with enhanced antitumor
      activities. A series of substituted benzaldehydes was selected based on earlier
      SAR studies and reacted with hydantoin to yield 11 new compounds . Compounds were
      evaluated for their antiproliferative, antimigratory and anti-invasive properties
      in vitro against the human mammary and prostate cancer cell lines MDA-MB-231 and
      PC-3, respectively. A Western blot analysis of the most active analog showed its
      ability to suppress the expression of the total levels of c-Met and FAK, with
      subsequent reduction of their phosphorylated (activated) levels in MDA-MB-231
      cells. In addition, also inhibited Brk, paxillin and Rac1 phosphorylation. was
      formulated using hydroxypropyl beta-cyclodextrin (HPCD) to improve its solubility
      and was further evaluated in a nude mice xenograft model using MDA-MB-231/GFP
      cells. PMH reduced breast tumor growth and suppressed Ki-67, CD31, p-Brk and p
      FAK expression in tumor samples. Thus, is a potential lead for the control of
      invasive breast malignancies. 

PMID- 24927151
TI  - Clostridium difficile infection in solid organ transplant recipients.
AB  - PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is one of the most
      common healthcare-associated infections, and the threat associated with CDI
      continues to grow in all patient populations. There is increasing evidence that
      CDI has a substantial impact on the morbidity and mortality in solid organ
      transplant (SOT) recipients. Furthermore, new diagnostic and treatment options
      and strategies for CDI have emerged over the last decade. The purpose of this
      review is to provide a general understanding of CDI and its evidence-based
      diagnosis and management strategies, with a focus on SOT recipients. RECENT
      FINDINGS: The incidence and severity of CDI have significantly increased since
      the year 2000. Studies have identified novel risk factors for CDI, and a new
      epidemic strain, the NAP1/BI/027, has emerged. Despite the development of newer
      testing methods and approaches, including nucleic acid amplification tests and
      testing algorithms, the optimal method for diagnosing CDI is an area of
      controversy. New agents for treating CDI are being developed, and the use of
      fecal microbiota transplantation to treat recurrent CDI in SOT recipients is also
      evolving. SUMMARY: CDI is a significant problem for SOT recipients. Further
      studies on diagnostic and therapeutic strategies with a focus on SOT recipients
      are needed to further improve patient outcomes.

PMID- 24927147
TI  - Molecular mechanism and treatment of viral hepatitis-related liver fibrosis.
AB  - Hepatic fibrosis is a wound-healing response to various chronic stimuli,
      including viral hepatitis B or C infection. Activated myofibroblasts,
      predominantly derived from the hepatic stellate cells (HSCs), regulate the
      balance between matrix metalloproteinases and their tissue inhibitors to maintain
      extracellular matrix homeostasis. Transforming growth factor-beta and platelet
      derived growth factor are classic profibrogenic signals that activate HSC
      proliferation. In addition, proinflammatory cytokines and chemokines coordinate
      macrophages, T cells, NK/NKT cells, and liver sinusoidal endothelial cells in
      complex fibrogenic and regression processes. In addition, fibrogenesis involves
      angiogenesis, metabolic reprogramming, autophagy, microRNA, and epigenetic
      regulations. Hepatic inflammation is the driving force behind liver fibrosis;
      however, host single nucleotide polymorphisms and viral factors, including the
      genotype, viral load, viral mutation, and viral proteins, have been associated
      with fibrosis progression. Eliminating the underlying etiology is the most
      crucial antifibrotic therapy. Growing evidence has indicated that persistent
      viral suppression with antiviral therapy can result in fibrosis regression,
      reduced liver disease progression, decreased hepatocellular carcinoma, and
      improved chances of survival. Preclinical studies and clinical trials are
      currently examining several investigational agents that target key fibrogenic
      pathways; the results are promising and shed light on this debilitating illness. 

PMID- 24927149
TI  - On the influence of crosslinker on template complexation in molecularly imprinted
      polymers: a computational study of prepolymerization mixture events with
      correlations to template-polymer recognition behavior and NMR spectroscopic
      studies.
AB  - Aspects of the molecular-level basis for the function of ethylene glycol
      dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic
      acid copolymers molecularly imprinted with (S)-propranolol have been studied
      using a series of all-component and all-atom molecular dynamics studies of the
      corresponding prepolymerization systems. The crosslinking agents were observed to
      contribute to template complexation, and the results were contrasted with
      previously reported template-recognition behavior of the corresponding polymers.
      Differences in the extent to which the two crosslinkers interacted with the
      functional monomer were identified, and correlations were made to polymer-ligand
      recognition behavior and the results of nuclear magnetic resonance spectroscopic
      studies studies. This study demonstrates the importance of considering the
      functional monomer-crosslinker interaction when designing molecularly imprinted
      polymers, and highlights the often neglected general contribution of crosslinker
      to determining the nature of molecularly imprinted polymer-template selectivity. 

PMID- 24927152
TI  - Development and assessment of a novel Arxula adeninivorans androgen screen (A
      YAS) assay and its application in analysis of cattle urine.
AB  - The novel A-YAS assay for the detection of androgenic activity in liquid samples
      such as urine has been developed and assessed. The assay is based on transgenic
      Arxula adeninivorans yeast cells as the bio-component. The cells were engineered
      to co-express the human androgen receptor (hAR) gene and the inducible phytase
      reporter gene (phyK, derived from Klebsiella sp. ASR1), under the control of an
      Arxula derived glucoamylase (GAA) promoter, which had been modified by the
      insertion of hormone-responsive elements (HREs). The Arxula
      transformation/expression platform Xplor(r)2 was used to select stable mitotic
      resistance marker free transformants and the most suitable cells were
      characterized for performance as a sensor bio-component. The assay is easy-to
      use, fast (6-25 h) and is currently the most sensitive yeast-based androgen
      screen with an EC50, limit of detection and of quantification values for 5alpha
      dihydrotestosterone (DHT) of 277.1+/-53.0, 56.5+/-4.1 and 76.5+/-6.7 ng L(-1),
      respectively. Furthermore, the assay allows the determination of androgenic and
      anti-androgenic activity of various compounds such as naturally occurring
      androgens and estrogens, pharmaceuticals and biocides. The robustness of the A
      YAS assay enables it to be used for analysis of complex samples such as urine.
      The results of the analysis of a number of cattle urine samples achieved by the A
      YAS assay correlate well with GC-MS analysis of the same samples.

PMID- 24927153
TI  - Protein electrochemistry using graphene-based nano-assembly: an ultrasensitive
      electrochemical detection of protein molecules via nanoparticle-electrode
      collisions.
AB  - We describe a new electrochemical detection approach towards single protein
      molecules (microperoxidase-11, MP-11), which are attached to the surface of
      graphene nanosheets. The non-covalently functionalized graphene nanosheets
      exhibit enhanced electroactive surface area, where amplified redox current is
      produced when graphene nanosheets collide with the electrode. 

PMID- 24927155
TI  - Peptides on the surface. PELDOR data for spin-labeled alamethicin F50/5 analogues
      on organic sorbent.
AB  - The PELDOR technique was used to obtain the spectra of distances between spin
      labels for mono and double TOAC substituted analogues of [Glu(OMe)(7,18,19)]
      alamethicin F50/5 (Alm') peptaibiotic on the surface of the organic sorbent Oasis
      HLB and in ethanol solution at 77 K. For the double-labeled Alm', the free
      radical probes are at positions 1 and 16 (Alm'1,16). The intra- and
      intermolecular contributions to the PELDOR time traces were separated, with
      regard to the fractality of the system studied. We established that on HLB the
      labeled Alm' molecules are prone to aggregation. The distance spectra for
      Alm'1,16 show that, in both adsorbed state and in ethanol solution, the
      peptaibiotic is predominantly folded in the alpha-helix conformation. We assign
      the asymmetry of the distance spectrum in both cases to the occurrence of an
      admixture of more elongated alpha/3(10)-helical conformers. The portion of these
      conformers is higher for the peptide adsorbed on HLB. We speculate that both the
      broadening of the basic spectrum line at r(max) = 2.0 nm and the increase in the
      contribution of elongated conformers might be associated with the spread of the
      peptaibiotic adsorption sites on HLB as compared with the more uniform Alm'1,16
      trap structure in frozen ethanol solution. The aggregates of mono-labeled Alm'1
      and Alm'16 also studied. The intermolecular distance spectrum for Alm'1 on HLB is
      shifted toward longer distances as compared with those of Alm'16. This result
      suggests that in the aggregates Alm' molecules are preferentially oriented with
      their C-terminal regions in the vicinity.

PMID- 24927154
TI  - Characterization of plasmids carrying oqxAB in bla(CTX-M)-negative Escherichia
      coli isolates from food-producing animals.
AB  - To study the characteristics of plasmids harboring oqxAB among bla(CTX-M)
      negative Escherichia coli isolates and search for oqxAB-harboring plasmids
      similar to plasmids carrying oqxAB-bla(CTX-M) reported previously, conjugation
      experiment was performed for 115 randomly selected oqxAB-positive but bla(CTX-M)
      negative E. coli isolates from diseased animals in Guangdong, China. S1 nuclease
      pulsed-field gel electrophoresis (PFGE) and southern blotting experiments were
      performed to investigate the location of oqxAB and other resistance genes. The
      EcoRI digestion profiles of the plasmids with oqxAB were also analyzed. The
      clonal relatedness of donor isolates was investigated by PFGE. In this study, 32
      oqxAB transconjugants were successfully obtained and most transconjugants showed
      multidrug resistances. Eleven replicon combination types were found in these
      transconjugants. floR and oqxAB were found on the same plasmids in all nine
      transconjugants resistant to florfenicol. The sequences between floR and oqxAB
      were identical in most transconjugants and the two genes were both linked with
      tnp in insertion sequences. Nine F18:A-:B1 plasmids with only oqxAB shared
      identical EcoRI digestion profiles and the profiles were also identical with that
      of a plasmid carrying oqxAB-bla(CTX-M) found previously. Co-transfer of plasmids
      carrying oqxAB and fosA3, respectively, was also observed in one isolate. This
      study demonstrates the dissemination of oqxAB among bla(CTX-M)-negative E. coli
      isolates was mainly mediated by identical F18:A-:B1 plasmids. A novel arrangement
      of regions between floR and oqxAB might play an important role in the
      dissemination of floR-oqxAB. This is the first description of the genetic
      environment of the relationship between oqxAB and floR in E. coli.

PMID- 24927156
TI  - Protective immunity and safety of a genetically modified influenza virus vaccine.
AB  - Recombinant influenza viruses are promising viral platforms to be used as antigen
      delivery vectors. To this aim, one of the most promising approaches consists of
      generating recombinant viruses harboring partially truncated neuraminidase (NA)
      segments. To date, all studies have pointed to safety and usefulness of this
      viral platform. However, some aspects of the inflammatory and immune responses
      triggered by those recombinant viruses and their safety to immunocompromised
      hosts remained to be elucidated. In the present study, we generated a recombinant
      influenza virus harboring a truncated NA segment (vNA-Delta) and evaluated the
      innate and inflammatory responses and the safety of this recombinant virus in
      wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired
      (RAG -/-) immune responses. Infection using truncated neuraminidase influenza
      virus was harmless regarding lung and systemic inflammatory response in wild type
      mice and was highly attenuated in KO mice. We also demonstrated that vNA-Delta
      infection does not induce unbalanced cytokine production that strongly
      contributes to lung damage in infected mice. In addition, the recombinant
      influenza virus was able to trigger both local and systemic virus-specific
      humoral and CD8+ T cellular immune responses which protected immunized mice
      against the challenge with a lethal dose of homologous A/PR8/34 influenza virus.
      Taken together, our findings suggest and reinforce the safety of using NA deleted
      influenza viruses as antigen delivery vectors against human or veterinary
      pathogens. 

PMID- 24927157
TI  - Energy metabolism in Mycobacterium gilvum PYR-GCK: insights from transcript
      expression analyses following two states of induction.
AB  - Mycobacterium gilvum PYR-GCK, a pyrene degrading bacterium, has been the subject
      of functional studies aimed at elucidating mechanisms related to its outstanding
      pollutant bioremediation/biodegradation activities. Several studies have
      investigated energy production and conservation in Mycobacterium, however, they
      all focused on the pathogenic strains using their various hosts as induction
      sources. To gain greater insight into Mycobacterium energy metabolism, mRNA
      expression studies focused on respiratory functions were performed under two
      different conditions using the toxic pollutant pyrene as a test substrate and
      glucose as a control substrate. This was done using two transcriptomic
      techniques: global transcriptomic RNA-sequencing and quantitative Real-Time PCR.
      Growth in the presence of pyrene resulted in upregulated expression of genes
      associated with limited oxygen or anaerobiosis in M. gilvum PYR-GCK. Upregulated
      genes included succinate dehydrogenases, nitrite reductase and various electron
      donors including formate dehydrogenases, fumarate reductases and NADH
      dehydrogenases. Oxidative phosphorylation genes (with respiratory chain complexes
      I, III -V) were expressed at low levels compared to the genes coding for the
      second molecular complex in the bacterial respiratory chain (fumarate reductase);
      which is highly functional during microaerophilic or anaerobic bacterial growth.
      This study reveals a molecular adaptation to a hypoxic mode of respiration during
      aerobic pyrene degradation. This is likely the result of a cellular oxygen
      shortage resulting from exhaustion of the oxygenase enzymes required for these
      degradation activities in M. gilvum PYR-GCK.

PMID- 24927159
TI  - Vibrational lifetimes of cyanide ion in aqueous solution from molecular dynamics
      simulations: intermolecular vs intramolecular accepting modes.
AB  - The lifetimes of the first vibrational state of (12)C(14)N(-) and (13)C(15)N(-)
      dissolved in H2O or D2O were calculated. The calculations were based on the
      Landau-Teller formula that puts the vibrational lifetimes in terms of the
      autocorrelation function of the force exerted on the C-N stretch by the remaining
      degrees of freedom. The force autocorrelation functions were calculated from
      classical molecular dynamics simulations of the four cyanide/water isotopomer
      combinations ((12)C(14)N(-)/H2O, (12)C(14)N(-)/D2O, (13)C(15)N(-)/H2O,
      (13)C(15)N(-)/D2O). The cyanide ion was described by a polarizable force field,
      and the water was described by either the rigid SPC/E model or the flexible
      SPC/Fw model, in order to compare two different types of accepting modes, namely,
      (1) intermolecular (translational and rotational) solvent accepting modes (rigid
      SPC/E water) and (2) intramolecular (vibrational) solvent accepting modes
      (flexible SPC/Fw water). Since quantum effects are expected to increase in size
      with increasing frequency mismatch between relaxing and accepting modes,
      different quantum correction factors were employed depending on the identity of
      the accepting modes, more specifically, the harmonic/Schofield quantum correction
      factor in the case of intermolecular accepting modes and the standard quantum
      correction factor in the case of intramolecular accepting modes. The lifetimes
      with either the rigid SPC/E or flexible SPC/Fw water models were found to be in
      good quantitative agreement with the experimentally measured values for all
      isotopomer combinations. Our results suggest that taking into account quantum
      effects on the vibrational energy relaxation of cyanide in aqueous solution can
      make the intermolecular pathway at least as likely as the intramolecular pathway.

PMID- 24927158
TI  - Scale-invariant neuronal avalanche dynamics and the cut-off in size
      distributions.
AB  - Identification of cortical dynamics strongly benefits from the simultaneous
      recording of as many neurons as possible. Yet current technologies provide only
      incomplete access to the mammalian cortex from which adequate conclusions about
      dynamics need to be derived. Here, we identify constraints introduced by sub
      sampling with a limited number of electrodes, i.e. spatial 'windowing', for well
      characterized critical dynamics-neuronal avalanches. The local field potential
      (LFP) was recorded from premotor and prefrontal cortices in two awake macaque
      monkeys during rest using chronically implanted 96-microelectrode arrays.
      Negative deflections in the LFP (nLFP) were identified on the full as well as
      compact sub-regions of the array quantified by the number of electrodes N (10
      95), i.e., the window size. Spatiotemporal nLFP clusters organized as neuronal
      avalanches, i.e., the probability in cluster size, p(s), invariably followed a
      power law with exponent -1.5 up to N, beyond which p(s) declined more steeply
      producing a 'cut-off' that varied with N and the LFP filter parameters. Clusters
      of size s<=N consisted mainly of nLFPs from unique, non-repeated cortical sites,
      emerged from local propagation between nearby sites, and carried spatial
      information about cluster organization. In contrast, clusters of size s>N were
      dominated by repeated site activations and carried little spatial information,
      reflecting greatly distorted sampling conditions. Our findings were confirmed in
      a neuron-electrode network model. Thus, avalanche analysis needs to be
      constrained to the size of the observation window to reveal the underlying scale
      invariant organization produced by locally unfolding, predominantly feed-forward
      neuronal cascades. 

PMID- 24927160
TI  - Exploiting intrinsic nanoparticle toxicity: the pros and cons of nanoparticle
      induced autophagy in biomedical research.

PMID- 24927161
TI  - Immobilization of hyaluronic acid on plasma-sprayed porous titanium coatings for
      improving biological properties.
AB  - In the present study, hyaluronic acid (HyA) was covalently immobilized onto
      titanium coatings to improve their biological properties. Diffuse reflectance
      Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were
      employed to characterize the HyA-modified titanium coating. HyA-modified titanium
      coatings possess better cell-material interaction, and human mesenchymal stem
      cells present good adhesive morphologies on the surface of TC-AAH. The results of
      subsequent cellular evaluation showed that the immobilization of HyA on titanium
      coatings could improve hMSC attachment, proliferation, and differentiation. In
      vivo evaluation of implants in rabbit femur condyle defect model showed
      improvements of early osseointegration and bone-to-implant contact of TC-AAH. In
      conclusion, immobilization of HyA could improve biological properties of titanium
      coatings. 

PMID- 24927162
TI  - Predictions for the future of kallikrein-related peptidases in molecular
      diagnostics.
AB  - Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine
      proteases. This multigene family hosts the most widely used cancer biomarker that
      is PSA-KLK3, with millions of tests performed annually worldwide. The present
      report provides an overview of the biomarker potential of the extended KLK family
      (KLK1-KLK15) in various disease settings and envisages approaches that could lead
      to additional KLK-driven applications in future molecular diagnostics. Particular
      focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels
      that provide enhanced diagnostic, prognostic and/or predictive accuracy in
      several human malignancies. Such panels have been described so far for prostate,
      ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non
      malignant disease settings, such as Alzheimer's disease and multiple sclerosis,
      is also commented upon. Predictions are given on the challenges and future
      directions regarding clinically oriented KLK research. 

PMID- 24927163
TI  - Cancer stem cell differentiation: TGFbeta1 and versican may trigger molecules for
      the organization of tumor spheroids.
AB  - Cancer stem cells (CSCs) have the ability to self-renew similar to normal stem
      cells. This process is linked with metastasis and resistance to chemotherapy and
      radiotherapy. In the present study, we constructed an in vitro differentiation
      model for CSCs. CSCs isolated and proliferated for one passage were maintained as
      monolayers or spheroid-forming cells with serum included media for
      differentiation process. Differentiation of adhesion molecules and cellular
      ultrastructural properties were investigated and compared in both monolayer and
      spheroid cultures. CD133+/CD44+ cancer-initiating cells were isolated from DU-145
      human prostate cancer cell line monolayer cultures and propagated as tumor
      spheroids and compared with the remaining heterogeneous cancer cell bulk
      population. Microarray-based gene expression analysis was applied to determine
      genes with differential expression and protein expression levels of candidates
      were analyzed by immunohistochemistry. Electron microscopy showed detailed
      analysis of morphology. TGFbeta1 was found to be significantly upregulated in
      monolayer CSCs. High expression levels of VCAN, COL7A1, ITGbeta3, MMP16, RPL13A,
      COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected
      when CSCs were maintained as serum-grown prostate CSC spheroids.
      Immunohistochemistry supported increased immunoreactivity of TGFbeta1 in
      monolayer cultures and VCAN in spheroids. CSCs were found to possess
      multipotential differentiation capabilities through upregulation and/or
      downregulation of their markers. TGFbeta1 is a triggering molecule, it stimulates
      versican, Col7A1, ITGbeta3 and, most importantly, the upregulation of versican
      was only detected in CSCs. Our data support a model where CSCs must be engaged by
      one or more signaling cascades to differentiate and initiate tumor formation.
      This mechanism occurs with intracellular and extracellular signals and it is
      possible that CSCc themselves may be a source for extracellular signaling. These
      molecules functioning in tumor progression and differentiation may help develop
      targeted therapy.

PMID- 24927164
TI  - Hospital economic impact from hemostatic matrix usage in cardiac surgery.
AB  - OBJECTIVE: Improved health outcomes can result in economic savings for hospitals
      and payers. While effectiveness of topical hemostatic agents in cardiac surgery
      has been demonstrated, evaluations of their economic benefit are limited. This
      study quantifies the cost consequences to hospitals, based on clinical outcomes,
      from using a flowable hemostatic matrix vs non-flowable topical hemostatic agents
      in cardiac surgery. RESEARCH DESIGN AND METHODS: Applying clinical outcomes from
      a prospective randomized clinical trial, a cost consequence framework was
      utilized to model the economic impact of comparator groups. From that study,
      clinical outcomes were obtained and analyzed for a flowable hemostatic matrix
      (FLOSEAL, Baxter Healthcare Corporation) vs non-flowable topical hemostats
      (SURGICEL Nu-Knit, Ethicon-Johnson & Johnson; GELFOAM, Pfizer). Costing analyses
      focused on the following outcomes: complications, blood transfusions, surgical
      revisions, and operating room (OR) time. Cardiac surgery costs were analyzed and
      expressed in 2012 US dollars based on available literature searches and US data.
      Comparator group variability in cost consequences (i.e., cost savings) was
      calculated based on annualized impact and scenario testing. RESULTS: RESULTS
      suggest that if a flowable hemostatic matrix (rather than a non-flowable
      hemostat) was utilized exclusively in 600 mixed cardiac surgeries annually, a
      hospital could improve patient outcomes by a reduction of 33 major complications,
      76 minor complications, 54 surgical revisions, 194 transfusions, and 242 h of OR
      time. These outcomes correspond to a net annualized cost consequence savings of
      $5.38 million, with complication avoidance as the largest contributor.
      CONCLUSIONS: This cost consequence framework and supportive modeling was used to
      evaluate the hospital economic impact of outcomes resulting from the usage of
      various hemostatic agents. These analyses support that cost savings can be
      achieved from routine use of a flowable hemostatic matrix, rather than a non
      flowable topical hemostat, in cardiac surgery.

PMID- 24927165
TI  - Vulnerability of breeding waterbirds to climate change in the Prairie Pothole
      Region, U.S.A.
AB  - The Prairie Pothole Region (PPR) of the north-central U.S. and south-central
      Canada contains millions of small prairie wetlands that provide critical habitat
      to many migrating and breeding waterbirds. Due to their small size and the
      relatively dry climate of the region, these wetlands are considered at high risk
      for negative climate change effects as temperatures increase. To estimate the
      potential impacts of climate change on breeding waterbirds, we predicted current
      and future distributions of species common in the PPR using species distribution
      models (SDMs). We created regional-scale SDMs for the U.S. PPR using Breeding
      Bird Survey occurrence records for 1971-2011 and wetland, upland, and climate
      variables. For each species, we predicted current distribution based on climate
      records for 1981-2000 and projected future distributions to climate scenarios for
      2040-2049. Species were projected to, on average, lose almost half their current
      habitat (-46%). However, individual species projections varied widely, from +8%
      (Upland Sandpiper) to -100% (Wilson's Snipe). Variable importance ranks indicated
      that land cover (wetland and upland) variables were generally more important than
      climate variables in predicting species distributions. However, climate variables
      were relatively more important during a drought period. Projected distributions
      of species responses to climate change contracted within current areas of
      distribution rather than shifting. Given the large variation in species-level
      impacts, we suggest that climate change mitigation efforts focus on species
      projected to be the most vulnerable by enacting targeted wetland management,
      easement acquisition, and restoration efforts. 

PMID- 24927167
TI  - Assessment of bacterial bph gene in Amazonian dark earth and their adjacent
      soils.
AB  - Amazonian Anthrosols are known to harbour distinct and highly diverse microbial
      communities. As most of the current assessments of these communities are based on
      taxonomic profiles, the functional gene structure of these communities, such as
      those responsible for key steps in the carbon cycle, mostly remain elusive. To
      gain insights into the diversity of catabolic genes involved in the degradation
      of hydrocarbons in anthropogenic horizons, we analysed the bacterial bph gene
      community structure, composition and abundance using T-RFLP, 454-pyrosequencing
      and quantitative PCR essays, respectively. Soil samples were collected in two
      Brazilian Amazon Dark Earth (ADE) sites and at their corresponding non
      anthropogenic adjacent soils (ADJ), under two different land use systems,
      secondary forest (SF) and manioc cultivation (M). Redundancy analysis of T-RFLP
      data revealed differences in bph gene structure according to both soil type and
      land use. Chemical properties of ADE soils, such as high organic carbon and
      organic matter, as well as effective cation exchange capacity and pH, were
      significantly correlated with the structure of bph communities. Also, the
      taxonomic affiliation of bph gene sequences revealed the segregation of community
      composition according to the soil type. Sequences at ADE sites were mostly
      affiliated to aromatic hydrocarbon degraders belonging to the genera
      Streptomyces, Sphingomonas, Rhodococcus, Mycobacterium, Conexibacter and
      Burkholderia. In both land use sites, shannon's diversity indices based on the
      bph gene data were higher in ADE than ADJ soils. Collectively, our findings
      provide evidence that specific properties in ADE soils shape the structure and
      composition of bph communities. These results provide a basis for further
      investigations focusing on the bio-exploration of novel enzymes with potential
      use in the biotechnology/biodegradation industry. 

PMID- 24927168
TI  - Enduring effects of evidence-based psychotherapies in acute depression and
      anxiety disorders versus treatment as usual at follow-up--a longitudinal meta
      analysis.
AB  - OBJECTIVE: This meta-analysis examined the enduring efficacy of evidence-based
      psychotherapies (EBP) in comparison to treatment as usual (TAU) by examining
      effects from termination to follow-up for acute anxiety and depression in an
      adult outpatient population. It was hypothesized that EBPs might extend their
      efficacy at follow-up assessment (Tolin, 2010). METHOD: Longitudinal multilevel
      meta-analyses were conducted that examined the magnitude of difference between
      EBP and TAU. Targeted (disorder-specific) outcomes were examined, along with
      dropout rates at follow-up assessments. RESULTS: A total of 15 comparisons
      (including 30 repeated effect sizes [ES]) were included in this meta-analysis
      (average of 8.9 month follow-up). Small to moderate ES differences were found to
      be in favor of EBPs at 0-4 month assessments (Hedges' g=0.40) and up to 12-18
      month assessments (g=0.20), indicating no extended efficacy at follow-up.
      However, the TAU-conditions were heterogeneous, ranging from absence of minimal
      mental health treatment to legitimate psychotherapeutic interventions provided by
      trained professionals, the latter of which resulted in smaller ES differences.
      Furthermore, samples where substance use comorbidities were not actively excluded
      indicated smaller ES differences. TAU-conditions produced slightly higher dropout
      rates than EBP-conditions. CONCLUSION: Findings indicate small and no extended
      superiority of EBP for acute depression and anxiety disorders in comparison to
      TAU at follow-up assessment. There are a limited number of studies investigating
      the transportability and lasting efficacy of EBP compared to TAU, especially to
      TAU with equivalent conditions between treatment groups.

PMID- 24927169
TI  - Efficacy and safety of Tai Chi for Parkinson's disease: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVE: In Parkinson's disease (PD), wearing off and side
      effects of long-term medication and complications pose challenges for
      neurologists. Although Tai Chi is beneficial for many illnesses, its efficacy for
      PD remains uncertain. The purpose of this review was to evaluate the efficacy and
      safety of Tai Chi for PD. METHODS: Randomized controlled trials (RCTs) of Tai Chi
      for PD were electronically searched by the end of December 2013 and identified by
      two independent reviewers. The tool from the Cochrane Handbook 5.1 was used to
      assess the risk of bias. A standard meta-analysis was performed using RevMan 5.2
      software. RESULTS: Ten trials with PD of mild-to-moderate severity were included
      in the review, and nine trials (n = 409) were included in the meta-analysis. The
      risk of bias was generally high in the blinding of participants and personnel.
      Improvements in the Unified Parkinson's Disease Rating Scale Part III (mean
      difference (MD) -4.34, 95% confidence interval (CI) -6.67--2.01), Berg Balance
      Scale (MD: 4.25, 95% CI: 2.83-5.66), functional reach test (MD: 3.89, 95% CI:
      1.73-6.04), Timed Up and Go test (MD: -0.75, 95% CI: -1.30--0.21), stride length
      (standardized MD: 0.56, 95% CI: 0.03-1.09), health-related quality of life
      (standardized MD: -1.10, 95% CI: -1.81--0.39) and reduction of falls were greater
      after interventions with Tai Chi plus medication. Satisfaction and safety were
      high. Intervention with Tai Chi alone was more effective for only a few balance
      and mobility outcomes. CONCLUSIONS: Tai Chi performed with medication resulted in
      promising gains in mobility and balance, and it was safe and popular among PD
      patients at an early stage of the disease. This provides a new evidence for PD
      management. More RCTs with larger sample size that carefully address blinding and
      prudently select outcomes are needed. PROSPERO registration number
      CRD42013004989.

PMID- 24927170
TI  - Alitretinoin: a useful agent in the treatment of hidradenitis suppurativa,
      especially in women of child-bearing age.
AB  - AIM: Despite a better insight into its pathogenesis, hidradenitis suppurativa
      (HS) remains very frustrating to treat. Acitretin has been described as one of
      the agents with the highest effective profile. Acitretin however, due to its
      teratogenicity and prolonged half-life (up to three years) is not an option in
      young women of fertile age who, unfortunately, are the target of this disease.
      Alitretinoin has a similar pharmacology action to acitretin, but much shorter
      half-life (only four weeks), making it a far much more attractive option compared
      to acitretin for women of child-bearing age. The aim of this paper was to
      evaluate the use of alitretinoin in treating recalcitrant cases of HS, which have
      not been responsive to standard treatments. METHODS: Fourteen patients (all
      female, of child-bearing age), who persistently failed traditional treatments,
      were treated with alitretinoin 10 mg/day for 24 weeks. The disease trend was
      evaluated by using both Sartorius and Dermatology Life Quality Index scores at
      time 0, at week 12 and at week 24. RESULTS: A significant improvement was
      recorded in 78.5% of the cases. CONCLUSION: Although more studies are necessary,
      this preliminary study shows that alitretinoin may have a role in the treatment
      of HS specifically in women of fertile age.

PMID- 24927171
TI  - Health-related quality of life in adult atopic dermatitis and psoriatic patients
      matched by disease severity.
AB  - BACKGROUND: Atopic dermatitis (AD) and psoriasis have significant negative impact
      on patients' lives. Objective of this study was to compare the impact of
      psoriasis and AD in adult patients matched by disease severity and to perform
      further validation of the Ukrainian versions of the DLQI and Skindex-16 in these
      skin conditions. METHODS: Sixty-three adult AD and 63 psoriatic patients matched
      by disease severity according to SCORAD and PASI were enrolled. Patients
      completed the Ukrainian versions of the DLQI and Skindex-16 questionnaires.
      Cronbach's alpha was used to measure internal consistency of the Ukrainian
      versions of the DLQI and Skindex-16. RESULTS: All three scales of Skindex-16 and
      the DLQI were internally reliable. Mean DLQI was 10.63 +/- 6.15 for AD patients
      and 11.59 +/- 7.18 for psoriatic patients (P=0.43). The highest scored question
      of the DLQI concerned symptoms tends the highest scored item for Skindex-16 was
      "frustration about skin condition". The DLQI item on treatment was scored higher
      by psoriatic patients (1.32 +/- 0.98 and AD = 0.73+/-0.79, P<0.001).
      "Functioning" scale of Skindex-16 was assessed higher by psoriatic patients in
      all clinical subgroups and "Emotions" scale in subgroup with mild disease
      severity. Skindex-16 item on itching was assessed higher by AD patients (3.65 +/-
      2.03 for AD and 2.92 +/- 1.95 for psoriatic patients, P<0.05) meanwhile, two
      other separate Skindex-16 items had higher impact on psoriatic patients: the
      effect of skin condition on desire to be with people (3.51 +/- 2.18 for psoriatic
      patients and 2.29 +/- 2.09 for AD patients, P<0.05) and skin condition making it
      hard to show the affection (3.51 +/- 2.18 for psoriatic patients and 2.24 +/-
      2.09 for AD patients, P<0.05). CONCLUSION: Psoriasis has higher effect on desire
      to be with people, showing affection and cause more problems with the treatment,
      meanwhile in AD itching cause higher negative impact on QoL. Even psoriatic
      patients with mild disease often may have large negative effect on their QoL that
      is not typical for AD patients.

PMID- 24927172
TI  - Early activation of fibroblasts during PDT treatment in leg ulcers.
AB  - BACKGROUND: This pilot study was aimed to assess the variations of some
      microscopical parameters in skin ulcers, caused by chronic venous insufficiency
      of the lower extremities (chronic leg ulcers), in 15 patients refractory to
      previous conventional treatments during photodynamic therapy (PDT). METHODS:
      Samples of control, wounded and PDT treated skin were taken and analyzed by
      immunohistochemistry. RESULTS: The cellular infiltrate, as well as the thickness
      of epidermis, vascularization, mast cell and fibroblast numbers, were increased
      in chronic wounds as compared to healthy skin. After completion of PDT,
      fibroblasts appeared further increased in number. Mast cells, closely clustered
      with fibroblasts, also showed an increase in their numbers, degranulation index
      and expression of basic fibroblast growth factor. CONCLUSIONS: The present
      findings support a primary role of fibroblasts in the wound healing process upon
      PDT treatment, given their early and intense reaction to injury. Mast cells seem
      to play an accessory yet important role, on the basis of their number and
      degranulation index variations and expression of basic FGF. In addition, the
      clustering of mast cells with fibroblasts around blood vessels suggest that these
      cells may stimulate angiogenesis and, in parallel, fibroblasts to secrete
      extracellular matrix during PDT therapy.

PMID- 24927173
TI  - Data sharing reveals complexity in the westward spread of domestic animals across
      Neolithic Turkey.
AB  - This study presents the results of a major data integration project bringing
      together primary archaeozoological data for over 200,000 faunal specimens
      excavated from seventeen sites in Turkey spanning the Epipaleolithic through
      Chalcolithic periods, c. 18,000-4,000 cal BC, in order to document the initial
      westward spread of domestic livestock across Neolithic central and western
      Turkey. From these shared datasets we demonstrate that the westward expansion of
      Neolithic subsistence technologies combined multiple routes and pulses but did
      not involve a set 'package' comprising all four livestock species including
      sheep, goat, cattle and pig. Instead, Neolithic animal economies in the study
      regions are shown to be more diverse than deduced previously using quantitatively
      more limited datasets. Moreover, during the transition to agro-pastoral economies
      interactions between domestic stock and local wild fauna continued. Through
      publication of datasets with Open Context (opencontext.org), this project
      emphasizes the benefits of data sharing and web-based dissemination of large
      primary data sets for exploring major questions in archaeology (Alternative
      Language Abstract S1). 

PMID- 24927174
TI  - Support vector machine classification of streptavidin-binding aptamers.
AB  - BACKGROUND: Synthesizing and characterizing aptamers with high affinity and
      specificity have been extensively carried out for analytical and biomedical
      applications. Few publications can be found that describe structure-activity
      relationships (SARs) of candidate aptamer sequences. METHODOLOGY: This paper
      reports pattern recognition with support vector machine (SVM) classification
      techniques for the identification of streptavidin-binding aptamers as "low" or
      "high" affinity aptamers. The SVM parameters C and gamma were optimized using
      genetic algorithms. Four descriptors, the topological descriptor PW4 (path/walk 4
      -Randic shape index), the connectivity index X3A (average connectivity index chi
      3), the topological charge index JGI2 (mean topological charge index of order 2),
      and the free energy E of the secondary structure, were used to describe the
      structures of candidate aptamer sequences from SELEX selection (Schutze et al.
      (2011) PLoS ONE (12):e29604). CONCLUSIONS: The predicted fractions of winning
      streptavidin-binding aptamers for ten rounds of SELEX conform to the aptamer
      evolutionary principles of SELEX-based screening. The feasibility of applying
      pattern recognition based on SVM and genetic algorithms for streptavidin-binding
      aptamers has been demonstrated.

PMID- 24927175
TI  - Tazarotene induces apoptosis in human basal cell carcinoma via activation of
      caspase-8/t-Bid and the reactive oxygen species-dependent mitochondrial pathway.
AB  - Previous studies suggest that tazarotene, a new member of the acetylenic class of
      RARbeta/gamma selective retinoids which is approved to treat a variety of skin
      diseases, exhibits an anti-proliferative effect in human basal cell carcinoma
      (BCC) by triggering caspase-dependent apoptosis. However, the detailed molecular
      mechanisms underlying the anti-tumor activity of tazarotene are poorly
      understood. This study aims at investigating the molecular mechanisms of
      tazarotene-induced apoptosis in human BCC cells. Our results are the first to
      demonstrate that tazarotene induces mitochondria-dependent cleavage of caspase-9
      and -3 and PARP in BCC cells by producing reactive oxygen species (ROS) and
      activating caspase-8 through both ROS and death receptor signaling. These events
      are accompanied by a decrease in BCL-2 and BCL-xl anti-apoptotic proteins as well
      as by survivin and XIAP, two IAP family members. Furthermore, our results
      presented for the first time that tazarotene triggers a convergence of the
      intrinsic and extrinsic apoptotic pathways via the caspase-8-truncated Bid
      signaling pathway. Collectively, these data provide insights into the molecular
      mechanisms underlying tazarotene-induced apoptosis in human BCC cells, suggesting
      that this compound is a potential anti-skin cancer drug. 

PMID- 24927176
TI  - TRAIL enhances apoptosis of human hepatocellular carcinoma cells sensitized by
      hepatitis C virus infection: therapeutic implications.
AB  - Hepatitis C virus (HCV) infection causes chronic liver diseases leading to
      hepatocellular carcinoma (HCC) and liver failure. We have previously shown that
      HCV sensitizes hepatocytes to mitochondrial apoptosis via the TRAIL death
      receptors DR4 and DR5. Although TRAIL and its receptors are selective targets for
      cancer therapy, their potential against HCC with chronic HCV infection has not
      been explored yet. Here we show that HCV induces DR4/DR5-dependent activation of
      caspase-8 leading to elevation of apoptotic signaling in infected cells and also
      present TRAIL effect in HCV-induced apoptotic signaling. HCV induced proteolytic
      cleavage of caspase-9 by stimulating DR4 and DR5, resulting in subsequent
      cleavage of caspase-3. Further, HCV-induced proteolytic cleavage in caspase-8,
      caspase-9, and caspase-3 was enhanced in the presence of recombinant TRAIL. HCV
      induced cleavage in caspase-9 and increase in caspase-3/7 activity was completely
      suppressed by silencing of either DR4 or DR5. Perturbing DR4/DR5-caspase-8
      signaling complex by silencing DR4 and DR5 or by chemical inhibitor specific to
      caspase-8 led to decrease of HCV-induced cleavage of poly(ADP-ribose) polymerase
      (PARP), a substrate for caspase-3 during apoptosis, indicating the functional
      role of caspase-8 in HCV-induced apoptotic signaling network. Furthermore, TRAIL
      enhanced PARP cleavage in apoptotic response induced by HCV infection, indicating
      the effect of TRAIL for the induction of selective apoptosis of HCC cells
      infected with HCV. Given the importance of apoptosis in HCC development, our data
      suggest that HCV-induced DR4 and DR5 may be considered as an attractive target
      for TRAIL therapy against HCC with chronic HCV infection. 

PMID- 24927177
TI  - A colorimetric and luminescent dual-modal assay for Cu(II) ion detection using an
      iridium(III) complex.
AB  - A novel iridium(III) complex-based chemosensor bearing the 5,6
      bis(salicylideneimino)-1,10-phenanthroline ligand receptor was developed, which
      exhibited a highly sensitive and selective color change from colorless to yellow
      and a visible turn-off luminescence response upon the addition of Cu(II) ions.
      The interactions of this iridium(III) complex with Cu2+ ions and thirteen other
      cations have been investigated by UV-Vis absorption titration, emission
      titration, and 1H NMR titration. 

PMID- 24927178
TI  - A RG-II type polysaccharide purified from Aconitum coreanum alleviates
      lipopolysaccharide-induced inflammation by inhibiting the NF-kappaB signal
      pathway.
AB  - Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum
      coreanum (Levl.) Rapaics have shown anti-inflammatory activity, which is strongly
      influenced by their chemical structures and chain conformations. However, the
      mechanisms of the anti-inflammatory effect by these polysaccharides have yet to
      be elucidated. A RG-II polysaccharide (KMPS-2E, Mw 84.8 kDa) was isolated from
      KMPS and its chemical structure was characterized by FT-IR and NMR spectroscopy,
      gas chromatography-mass spectrometry and high-performance liquid chromatography.
      The backbone of KMPS-2E consisted of units of [->6) -beta-D-Galp (1->3)-beta-L
      Rhap-(1->4)-beta-D-GalpA-(1->3)-beta-D-Galp-(1->] with the side chain ->5)-beta-D
      Arap (1->3, 5)-beta-D-Arap (1-> attached to the backbone through O-4 of (1->3,4)
      L-Rhap. T-beta-D-Galp is attached to the backbone through O-6 of (1->3,6)-beta-D
      Galp residues and T-beta-D-Ara is connected to the end group of each chain. The
      anti-inflammatory effects of KMPS-2E and the underlying mechanisms using
      lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and carrageenan-induced
      hind paw edema were investigated. KMPS-2E (50, 100 and 200 ug/mL) inhibits iNOS,
      TLR4, phospho-NF-kappaB-p65 expression, phosphor-IKK, phosphor-IkappaB-alpha
      expression as well as the degradation of IkappaB-alpha and the gene expression of
      inflammatory cytokines (TNF-alpha, IL-1beta, iNOS and IL-6) mediated by the NF
      kappaB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced
      activation of NF-kappaB as assayed by electrophorectic mobility shift assay
      (EMSA) in a dose-dependent manner and it reduced NF-kappaB DNA binding affinity
      by 62.1% at 200 ug/mL. In rats, KMPS-2E (200 mg/kg) can significantly inhibit
      carrageenan-induced paw edema as ibuprofen (200 mg/kg) within 3 h after a single
      oral dose. The results indicate that KMPS-2E is a promising herb-derived drug
      against acute inflammation.

PMID- 24927179
TI  - Development and evaluation of small peptidomimetic ligands to protease-activated
      receptor-2 (PAR2) through the use of lipid tethering.
AB  - Protease-activated receptor-2 (PAR2) is a G-Protein Coupled Receptor (GPCR)
      activated by proteolytic cleavage to expose an attached, tethered ligand
      (SLIGRL). We evaluated the ability for lipid-tethered-peptidomimetics to activate
      PAR2 with in vitro physiological and Ca2+ signaling assays to determine minimal
      components necessary for potent, specific and full PAR2 activation. A known PAR2
      activating compound containing a hexadecyl (Hdc) lipid via three polyethylene
      glycol (PEG) linkers (2at-LIGRL-PEG3-Hdc) provided a potent agonist starting
      point (physiological EC50 = 1.4 nM; 95% CI: 1.2-2.3 nM). In a set of truncated
      analogs, 2at-LIGR-PEG3-Hdc retained potency (EC50 = 2.1 nM; 1.3-3.4 nM) with
      improved selectivity for PAR2 over Mas1 related G-protein coupled receptor type
      C11, a GPCR that can be activated by the PAR2 peptide agonist, SLIGRL-NH2. 2at
      LIG-PEG3-Hdc was the smallest full PAR2 agonist, albeit with a reduced EC50 (46
      nM; 20-100 nM). 2at-LI-PEG3-Hdc retained specific activity for PAR2 with reduced
      EC50 (310 nM; 260-360 nM) but displayed partial PAR2 activation in both
      physiological and Ca2+ signaling assays. Further truncation (2at-L-PEG3-Hdc and
      2at-PEG3-Hdc) eliminated in vitro activity. When used in vivo, full and partial
      PAR2 in vitro agonists evoked mechanical hypersensitivity at a 15 pmole dose
      while 2at-L-PEG3-Hdc lacked efficacy. Minimum peptidomimetic PAR2 agonists were
      developed with known heterocycle substitutes for Ser1 (isoxazole or
      aminothiazoyl) and cyclohexylalanine (Cha) as a substitute for Leu2. Both
      heterocycle-tetrapeptide and heterocycle-dipeptides displayed PAR2 specificity,
      however, only the heterocycle-tetrapeptides displayed full PAR2 agonism. Using
      the lipid-tethered-peptidomimetic approach we have developed novel structure
      activity relationships for PAR2 that allows for selective probing of PAR2
      function across a broad range of physiological systems.

PMID- 24927180
TI  - Towards a quantitative OCT image analysis.
AB  - BACKGROUND: Optical coherence tomography (OCT) is an invaluable diagnostic tool
      for the detection and follow-up of retinal pathology in patients and experimental
      disease models. However, as morphological structures and layering in health as
      well as their alterations in disease are complex, segmentation procedures have
      not yet reached a satisfactory level of performance. Therefore, raw images and
      qualitative data are commonly used in clinical and scientific reports. Here, we
      assess the value of OCT reflectivity profiles as a basis for a quantitative
      characterization of the retinal status in a cross-species comparative study.
      METHODS: Spectral-Domain Optical Coherence Tomography (OCT), confocal Scanning
      Laser Ophthalmoscopy (SLO), and Fluorescein Angiography (FA) were performed in
      mice (Mus musculus), gerbils (Gerbillus perpadillus), and cynomolgus monkeys
      (Macaca fascicularis) using the Heidelberg Engineering Spectralis system, and
      additional SLOs and FAs were obtained with the HRA I (same manufacturer).
      Reflectivity profiles were extracted from 8-bit greyscale OCT images using the
      ImageJ software package (http://rsb.info.nih.gov/ij/). RESULTS: Reflectivity
      profiles obtained from OCT scans of all three animal species correlated well with
      ex vivo histomorphometric data. Each of the retinal layers showed a typical
      pattern that varied in relative size and degree of reflectivity across species.
      In general, plexiform layers showed a higher level of reflectivity than nuclear
      layers. A comparison of reflectivity profiles from specialized retinal regions
      (e.g. visual streak in gerbils, fovea in non-human primates) with respective
      regions of human retina revealed multiple similarities. In a model of Retinitis
      Pigmentosa (RP), the value of reflectivity profiles for the follow-up of
      therapeutic interventions was demonstrated. CONCLUSIONS: OCT reflectivity
      profiles provide a detailed, quantitative description of retinal layers and
      structures including specialized retinal regions. Our results highlight the
      potential of this approach in the long-term follow-up of therapeutic strategies.

PMID- 24927182
TI  - Endometrial ossification causing secondary infertility.

PMID- 24927183
TI  - The crown initiative: journal editors invite researchers to develop core outcomes
      in women's health.

PMID- 24927184
TI  - 34 weeks of gestation-lost in translation.

PMID- 24927181
TI  - Genome-wide association study identifies three novel susceptibility loci for
      severe Acne vulgaris.
AB  - Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo
      sebaceous unit. Here we perform a genome-wide association analysis in the United
      Kingdom, comparing severe cases of acne (n=1,893) with controls (n=5,132). In a
      second stage, we genotype putative-associated loci in a further 2,063 acne cases
      and 1,970 controls. We identify three genome-wide significant associations:
      11q13.1 (rs478304, Pcombined=3.23 * 10(-11), odds ratio (OR) = 1.20), 5q11.2
      (rs38055, P(combined) = 4.58 * 10(-9), OR = 1.17) and 1q41 (rs1159268,
      P(combined) = 4.08 * 10(-8), OR = 1.17). All three loci contain genes linked to
      the TGFbeta cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of
      OVOL1 and TFGB2 have decreased expression in affected compared with normal skin.
      Collectively, these data support a key role for dysregulation of TGFbeta-mediated
      signalling in susceptibility to acne.

PMID- 24927185
TI  - Test uptake and case detection of syphilis, HIV, and hepatitis C among women
      undergoing prenatal screening in British Columbia, 2007 to 2011.
AB  - OBJECTIVE: Test uptake and case detection trends for rubella, syphilis, HIV, and
      hepatitis C (HCV) were compared among the 2007 to 2011 cohort of women undergoing
      prenatal testing in British Columbia. Analysis involved linkage of provincially
      centralized laboratory and surveillance data to assess prenatal test uptake and
      rates of newly diagnosed versus prevalent infections. METHODS: We included
      prenatal specimens submitted from BC women aged 16 to 45 years in 2007 to 2011.
      Laboratory records were linked to provincial surveillance systems to identify
      confirmed maternal syphilis and HIV cases. Previous positive status was
      determined for HIV and HCV if a prior confirmed case was identified from
      laboratory records. We determined rates of HIV and HCV newly identified at
      prenatal screening (new diagnoses per 100 000 per year). Prevalence for HIV and
      HCV was the sum of all new and prior diagnoses (prevalence per 100 000 per year).
      RESULTS: Of 233 203 women, 96.9% were screened for rubella, 93.3% for syphilis,
      93.8% for HIV, and 21.5% for HCV. From 2007 to 2011, the overall rates of new
      diagnoses were 15.4, 5.1, and 82.8 cases per 100 000 per year for syphilis, HIV,
      and HCV, respectively. The overall prevalence was 45.9 and 551.5 cases per 100
      000 per year for HIV and HCV, respectively (0.05% and 0.6%). From 2007 to 2011,
      new diagnoses of HCV decreased 40% from 106.0 to 62.1 cases per 100 000 per year.
      HCV prevalence did not change and increased with maternal age. CONCLUSION: This
      study links surveillance and laboratory data to provide a provincial picture of
      prenatal screening test uptake and case detection, with the advantage of
      distinguishing new from prior diagnoses. This information can help guide prenatal
      communicable disease screening policy.

PMID- 24927186
TI  - Evaluation of the NovaSure endometrial ablation procedure in women with uterine
      cavity length over 10 cm.
AB  - OBJECTIVE: To evaluate procedure-related adverse events, post-procedure menstrual
      bleeding status, and surgical re-intervention in women with a sounded uterine
      length > 10 cm compared to women with a sounded uterine length <= 10 cm who
      underwent the NovaSure endometrial ablation procedure. METHODS: We conducted a
      retrospective cohort study of 188 women from a Canadian community-based
      gynaecology practice. Eighty-seven women had a sounded uterine length > 10 cm,
      and 101 patients had a sounded length <= 10 cm. Procedure-related adverse events,
      post-procedure menstrual bleeding status, and surgical re-interventions were
      compared between groups. RESULTS: Mean uterine sounding lengths were 11.0 +/- 0.6
      cm and 8.9 +/- 0.8 cm in the > 10 cm and <= 10 cm groups, respectively. There
      were no differences between the groups in demographic characteristics or
      gynaecologic history, with the exception of higher BMI in the > 10 cm group and a
      greater prevalence of dysmenorrhea in the <= 10 cm group. Overall, 44.1% of all
      participants had been unsuccessfully treated with hormonal therapy, and 20.7% had
      failed non-hormonal treatment before the ablation procedure. The remaining 35.2%
      of participants had declined alternative therapy and proceeded directly to
      endometrial ablation. No serious procedure-related adverse events occurred in
      either group. Menstrual bleeding status at follow-up at 30.4 +/- 15.3 months (>
      10 cm group) and 30.5 +/- 15.5 months (<= 10 cm group) was not different between
      the groups (P = 0.85). In women who did not undergo surgical re-intervention
      after the initial ablation, amenorrhea was reported by 51.9% in the > 10 cm group
      and 65.9% in the <= 10 cm group. CONCLUSION: The NovaSure endometrial ablation
      procedure was associated with successful menstrual bleeding outcomes in women
      with sounded uterine length > 10 cm. No serious procedure-related adverse events
      occurred, and the need for surgical re-intervention was low. There was no
      significant difference in bleeding rates between the > 10 cm and <= 10 cm uterine
      length cohorts.

PMID- 24927187
TI  - Massive hemorrhage following thrombolysis for postpartum pulmonary embolism with
      cardiac arrest.
AB  - BACKGROUND: Cardiac arrest following a massive pulmonary embolism in pregnancy or
      the puerperium is a rare and catastrophic event. CASE: We describe a case of
      massive pulmonary embolism with cardiac arrest in a 36-year-old patient,
      presenting 48 hours postpartum. She was treated with thrombolytic therapy and
      suffered a massive hemorrhage thereafter, which was compounded by disseminated
      intravascular coagulation. Following an emergency hysterectomy and massive blood
      product transfusion, she survived with no neurological sequelae. The medical team
      present had participated in two simulation sessions with similar scenarios in the
      weeks before the event. CONCLUSION: To our knowledge, this is only the fifth case
      reported in the literature on thrombolytic therapy in the postpartum period, and
      of these has the most severe hemorrhagic complication. An effective
      multidisciplinary approach to such a complex situation can be acquired through
      simulation-based training.

PMID- 24927188
TI  - Concurrent parathyroidectomy and caesarean section in the third trimester.
AB  - BACKGROUND: Primary hyperparathyroidism is the most common cause of hypercalcemia
      in the general population. It is a rare complication of pregnancy that is
      difficult for clinicians to recognize, yet it can have important and devastating
      effects for both mother and baby. CASE: A 27-year-old primigravida at 32+3 weeks'
      gestation had a serum calcium level in excess of 2.75 mmol/L and evidence of
      HELLP syndrome. She underwent concurrent parathyroidectomy and Caesarean section.
      Neither the mother nor the neonate developed hypocalcemia postoperatively. The
      mother's parathyroid tissue was pathologically atypical, and a left
      hemithyroidectomy was performed at three months postpartum. CONCLUSION: When
      hyperparathyroidism is diagnosed in the third trimester, concurrent
      parathyroidectomy and Caesarean section is a safe and reasonable option for
      management. This should be performed by a multidisciplinary team with careful
      monitoring of the calcium levels of both mother and neonate after surgery.

PMID- 24927189
TI  - The fetal safety of statins: a systematic review and meta-analysis.
AB  - Although an initial case series suggested that use of statins in pregnancy
      carried teratogenic risk, a recent meta-analysis of controlled observational
      studies has failed to corroborate this. A large number of potentially beneficial
      uses of statins in pregnant women have prompted a new evaluation of the risk
      benefit ratio of these agents in pregnancy. 

PMID- 24927190
TI  - Fake it till you make it: Policymaking and assisted human reproduction in Canada.
AB  - The Assisted Human Reproduction Act (AHR Act) came into effect in 2004. The AHR
      Act stipulates in s.12 that no reimbursement of expenditures incurred in the
      course of donating gametes, maintaining or transporting in vitro embryos, or
      providing surrogacy services is permitted, except in accordance with the
      regulations and with receipts. Ten years later, Health Canada still has not
      drafted the regulations governing reimbursement. Section 12 is therefore still
      not in force. Health Canada and others have asserted that there is a Health
      Canada policy on reimbursement and that reimbursement with receipts is legally
      permissible. We dispute the existence of such a policy and its legitimacy (if it
      exists). We also challenge the decision by Health Canada not to produce
      regulations and thereby make it possible for Parliament to bring s.12 into force.
      This intentional lack of action is worrisome on at least two fronts. First, it
      sidesteps the processes required for regulations and thereby ducks the
      Parliamentary oversight very deliberately built into the AHR Act. Second, it
      leaves Canadians who provide and who access assisted human reproduction uncertain
      about what is and is not permitted, and therefore fearful of, or at risk of,
      prosecution. We conclude that Health Canada should take the steps necessary to
      put regulations in front of Parliament so that Parliament will then be able to
      pass regulations and bring s.12 into force. Canadians should demand no less. 

PMID- 24927191
TI  - Assisted reproductive therapy in women with higher body mass index.

PMID- 24927192
TI  - Non-invasive prenatal testing: ethics and policy considerations.
AB  - New technologies analyzing fetal DNA in maternal blood have led to the wide
      commercial availability of non-invasive prenatal testing (NIPT). We present here
      for clinicians the ethical and policy issues related to an emerging practice
      option. Although NIPT presents opportunities for pregnant women, particularly
      women who are at increased risk of having a baby with an abnormality or who are
      otherwise likely to access invasive prenatal testing, NIPT brings significant
      ethics and policy challenges. The ethical issues include multiple aspects of
      informed decision-making, such as access to counselling about the possible
      results of the test in advance of making a decision about participation in NIPT.
      Policy considerations include issues related to offering and promoting a
      privately available medical strategy in publicly funded institutions. Ethics and
      policy considerations merge in NIPT with regard to sex selection and support for
      persons living with disabilities. 

PMID- 24927194
TI  - Characterization of EGFR family gene aberrations in cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a highly lethal malignancy of the biliary tract with
      very few treatment options. Epidermal growth factor receptor (EGFR) and human
      epidermal growth factor receptor (HER2) have been considered as potential
      therapeutic targets in CCA. In the present study, we attempted to clarify the
      clinicopathological significance of all EGFR family members, EGFR, HER2, HER3 and
      HER4, across the full spectrum of CCAs. Immunohistochemistry and FISH were
      performed to validate expressions and genetic aberrations of these molecules
      retrospectively in 175 CCA patients. EGFR, HER3 and HER4 were overexpressed in 20
      (30.8%), 8 (12.3%) and 41 (63.1%) of the 65 intrahepatic cholangiocarcinomas
      (IHCCs), and in 23 (20.9%), 13 (11.8%) and 62 (56.4%) of the 110 extrahepatic
      cholangiocarcinomas (EHCCs), respectively. Overexpression of HER2 was exclusively
      identified in EHCCs, among which the rate was 4.5% (5/110). A significant
      association was identified between EGFR amplification and EGFR overexpression
      (P=0.002). Similarly, HER2 amplification was strongly associated with HER2
      overexpression (P<0.001). Multivariate analysis suggested that EGFR
      overexpression is an independent prognostic factor in IHCC, but not in EHCC cases
      [HR (95% CI): 3.689 (1.253-10.587), P=0.018]. Notably, for the first time, we
      demonstrated HER4 expression is a prognostic factor in EGFR-negative IHCC
      patients. In vitro data further suggested a tumor-suppressor role of HER4 in CCA.
      siRNA knockdown of HER4 significantly increased RBE cell migration and invasion.
      By contrast, HER4 overexpression decreased proliferation of HuCCT-1 cells and
      their migratory and invasive capacity. In summary, our results revealed
      expression of the EGFR family members in CCA development and progression. CCAs
      differentially express HER2 protein based on tumor location. HER4 expression
      status allows stratification of CCA patients into different survival categories.

PMID- 24927193
TI  - Venous thromboembolism and antithrombotic therapy in pregnancy.
AB  - OBJECTIVE: To present an approach, based on current evidence, for the diagnosis,
      treatment, and thromboprophylaxis of venous thromboembolism in pregnancy and
      postpartum. EVIDENCE: Published literature was retrieved through searches of
      PubMed, Medline, CINAHL, and The Cochrane Library from November 2011 to July 2013
      using appropriate controlled vocabulary (e.g. pregnancy, venous thromboembolism,
      deep vein thrombosis, pulmonary embolism, pulmonary thrombosis) and key words
      (e.g., maternal morbidity, pregnancy complications, thromboprophylaxis,
      antithrombotic therapy). Results were restricted to systematic reviews,
      randomized control trials/controlled clinical trials, and observational studies
      published in English or French. There were no date restrictions. Grey
      (unpublished) literature was identified through searching the websites of
      clinical practice guideline collections, clinical trial registries, and national
      and international medical specialty societies. VALUES: The quality of evidence in
      this document was rated using the criteria described in the Report of the
      Canadian Task Force on Preventative Health Care (Table 1).

PMID- 24927196
TI  - Catalytic, nucleophilic allylation of aldehydes with 2-substituted allylic
      acetates: carbon-carbon bond formation driven by the water-gas shift reaction.
AB  - The ruthenium-catalyzed allylation of aldehydes with allylic acetates has been
      expanded to incorporate substituents at the 2-position of the allylic components.
      Allylic acetates bearing a variety of substituents (CO2-t-Bu, COMe, Ph, CH(OEt)2,
      and Me) undergo high-yielding additions with aromatic, alpha,beta-unsaturated,
      and aliphatic aldehydes. The conditions of the reaction were found to be mild (75
      degrees C, 24-48 h) and only required the use of 2-3 mol % of the triruthenium
      dodecacarbonyl catalyst under 40-80 psi of CO. The stoichiometries of water and
      allylic acetate employed were found to be critical to reaction efficiency. 

PMID- 24927195
TI  - Epidemiology of road traffic incidents in Peru 1973-2008: incidence, mortality,
      and fatality.
AB  - BACKGROUND: The epidemiological profile and trends of road traffic injuries
      (RTIs) in Peru have not been well-defined, though this is a necessary step to
      address this significant public health problem in Peru. The objective of this
      study was to determine trends of incidence, mortality, and fatality of RTIs in
      Peru during 1973-2008, as well as their relationship to population trends such as
      economic growth. METHODS AND FINDINGS: Secondary aggregated databases were used
      to estimate incidence, mortality and fatality rate ratios (IRRs) of RTIs. These
      estimates were standardized to age groups and sex of the 2008 Peruvian
      population. Negative binomial regression and cubic spline curves were used for
      multivariable analysis. During the 35-year period there were 952,668 road traffic
      victims, injured or killed. The adjusted yearly incidence of RTIs increased by
      3.59 (95% CI 2.43-5.31) on average. We did not observe any significant trends in
      the yearly mortality rate. The total adjusted yearly fatality rate decreased by
      0.26 (95% CI 0.15-0.43), while among adults the fatality rate increased by 1.25
      (95% CI 1.09-1.43). Models fitted with splines suggest that the incidence follows
      a bimodal curve and closely followed trends in the gross domestic product (GDP)
      per capita. CONCLUSIONS: The significant increasing incidence of RTIs in Peru
      affirms their growing threat to public health. A substantial improvement of
      information systems for RTIs is needed to create a more accurate epidemiologic
      profile of RTIs in Peru. This approach can be of use in other similar low and
      middle-income settings to inform about the local challenges posed by RTIs.

PMID- 24927199
TI  - Editorial.

PMID- 24927197
TI  - Systemic sclerosis immunoglobulin induces growth and a pro-fibrotic state in
      vascular smooth muscle cells through the epidermal growth factor receptor.
AB  - OBJECTIVE: It has been suggested that autoantibodies in systemic sclerosis (SSc)
      may induce the differentiation of cultured fibroblasts into myofibroblasts
      through platelet-derived growth factor receptor (PDGFR) activation. The present
      study aims to characterize the effects of SSc IgG on vascular smooth muscle cells
      (VSMCs) and to determine if stimulatory autoantibodies directed to the PDGFR can
      be detected, and whether they induce a profibrotic response in primary cultured
      VSMCs. METHODS: Cultured VSMCs were exposed to IgG fractions purified from SSc
      patient or control sera. VSMC responses were then analyzed for ERK1/2 and Akt
      phosphorylation, PDGFR immunoprecipitation, cellular proliferation, protein
      synthesis, and pro-fibrotic changes in mRNA expression. RESULTS: Stimulatory
      activity in IgG fractions was more prevalent and intense in the SSc samples. SSc
      IgG immunoprecipitated the PDGFR with greater avidity than control IgG.
      Interestingly, activation of downstream signaling events (e.g. Akt, ERK1/2) was
      independent of PDGFR activity, but required functional EGFR. We also detected
      increased protein synthesis in response to SSc IgG (p<0.001) and pro-fibrotic
      changes in gene expression (Tgfb1 +200%; Tgfb2 -23%; p<0.001)) in VSMCs treated
      with SSc IgG. CONCLUSION: When compared to control IgG, SSc IgG have a higher
      stimulation index in VSMCs. Although SSc IgG interact with the PDGFR, the
      observed remodeling signaling events occur through the EGFR in VSMC. Our data
      thus favour a model of transactivation of the EGFR by SSc-derived PDGFR
      autoantibodies and suggest the use of EGFR inhibitors in future target
      identification studies in the field of SSc.

PMID- 24927198
TI  - Long-term exposure to low-level arsenic in drinking water and diabetes incidence:
      a prospective study of the diet, cancer and health cohort.
AB  - BACKGROUND: Established causes of diabetes do not fully explain the present
      epidemic. High-level arsenic exposure has been implicated in diabetes risk, but
      the effect of low-level arsenic exposure in drinking water remains unclear.
      OBJECTIVE: We sought to determine whether long-term exposure to low-level arsenic
      in drinking water in Denmark is associated with an increased risk of diabetes
      using a large prospective cohort. METHODS: During 1993-1997, we recruited 57,053
      persons. We followed each cohort member for diabetes occurrence from enrollment
      until 31 December 2006. We traced and geocoded residential addresses of the
      cohort members and used a geographic information system to link addresses with
      water-supply areas. We estimated individual exposure to arsenic using all
      addresses from 1 January 1971 until the censoring date. Cox proportional hazards
      models were used to model the association between arsenic exposure and diabetes
      incidence, separately for two definitions of diabetes: all cases and a more
      strict definition in which cases of diabetes based solely on blood glucose
      results were excluded. RESULTS: Over a mean follow-up period of 9.7 years for
      52,931 eligible participants, there were a total of 4,304 (8.1%) diabetes cases,
      and 3,035 (5.8%) cases of diabetes based on the more strict definition. The
      adjusted incidence rate ratios (IRRs) per 1-MUg/L increment in arsenic levels in
      drinking water were as follows: IRR = 1.03 (95% CI: 1.01, 1.06) and IRR = 1.02
      (95% CI: 0.99, 1.05) for all and strict diabetes cases, respectively.
      CONCLUSIONS: Long-term exposure to low-level arsenic in drinking water may
      contribute to the development of diabetes.

PMID- 24927200
TI  - Limitations of epidemiological field data for mental health policy decisions.

PMID- 24927201
TI  - Pharmacological treatment of schizophrenia resistant to first-line treatment: a
      critical systematic review and meta-analysis.
AB  - Schizophrenia resistance to conventional antipsychotics is a common phenomenon.
      In 5-25% of cases, satisfactory treatment response is not achieved, and
      intolerance to conventional antipsychotics occurs in 5-20% of patients. Numerous
      reasons for refractoriness have been proposed. However, up to now only a few
      pharmacological agents have been found useful in the treatment of schizophrenia
      resistant to conventional antipsychotics. This paper critically reviews quality
      assessed trials on the pharmacological treatment of refractory schizophrenia.
      Randomized blinded trials of conventional antipsychotics at high doses, atypical
      antipsychotics, lithium, propranolol, and agents not traditionally used in the
      treatment of schizophrenia are reviewed. On the basis of the methodologically
      sound studies included, we conclude that only clozapine has proved to be
      clinically effective in the treatment of refractory schizophrenia. In the short
      term, the odds ratio for clinical improvement on clozapine treatment when
      compared to conventional treatment is calculated to be 2.4 (95% confidence
      interval [CI] 1.7-3.5) and the number of patients needed to treat (NNT) is 7 (95%
      CI 5-13). In single inconclusive trials, olanzapine and risperidone have been
      found as effective as clozapine. In order to establish the usefulness of other
      pharmacological treatments, more randomized clinical trials are needed. 

PMID- 24927202
TI  - Antidepressant treatment of juvenile depression.
AB  - Although depression is increasingly recognized in children and adolescents, these
      groups have responded to conventional tricyclic antidepressants less robustly
      than depressed adults. Emerging research suggests that juvenile depression may
      respond better to serotonergic and atypical pharmacologic agents, so guidelines
      for selection and administration of these agents are provided. 

PMID- 24927203
TI  - A longitudinal study of positive symptoms in schizo-affective and paranoid
      schizophrenia.
AB  - The purpose of our work was studying the evolution of positive psychopathological
      symptoms in patients who had suffered from schizo-affective (N=146) and paranoid
      schizophrenia (N=74) (according to ICD-9CM) for at least 5 years. Using the list
      of syndromes taken from the Present State Examination, we retrospectively
      analyzed 2118 relapses registered in these patients' life during their illness
      (mean 18.1 years). According to our data, when the course of schizo-affective and
      paranoid schizophrenia incorporates definite periods of remission, there is a
      tendency towards a simplification of positive symptoms: 1.for 26.4% of the
      patients, the illness manifested itself in infrequent relapses (once in 4-5 years
      or less); 2. in 45.9% of the patients (those who displayed prominent regressive
      tendencies) psychotic symptoms were replaced by symptoms of affective, primarily
      depressive, type; 3. in 18.6% of the patients the illness took the form of
      recurring uniform attacks; 4. only in a mere 9.1% of the patients was the
      disorder diagnosed as progressive; and 5. a tendency to improvement and favorable
      prognosis was more pronounced in schizo-affective schizophrenia patients than in
      patients with paranoid schizophrenia (69.9% vs 54.1%, P<0.05). 

PMID- 24927204
TI  - Birth distribution of schizophrenic patients in Japan (Tochigi).
AB  - The monthly birth distribution of schizophrenic inpatients was examined in the
      Tochigi prefecture, Japan. A significant excess (26%) above the expected birth
      counts was found for patients born in the winter months (December-February).
      These data are consistent with the previous reports from European and North
      American countries. 

PMID- 24927205
TI  - A memory clinic in a department of old-age psychiatry: Its role in clinical and
      academic research.
AB  - Memory clinics are specialist outpatient services offering assessment and
      evaluation in clinical practice. Memory clinics have been criticized for being
      preoccupied with research. We analysed the outcomes of 405 referrals to a memory
      clinic, providing a framework for discussion of the contributions of research to
      clinical practice. Of the 80% of referrals receiving a formal diagnosis, one
      third were recruited on to treatment studies, contributing to clinical research.
      The remaining two-thirds of patients referred were followed up by specialized
      care services, and findings from assessment procedures were used to contribute
      towards academic research. These findings are discussed with reference to the
      role of research for a memory clinic in clinical practice. The benefits of
      clinical research are noted, in relation to the percentage of patients involved.
      The nature of academic research is clarified; it is a dual process, with findings
      both aiding clinical research and contributing to the body of knowledge about
      dementia as a possible disease process. It is concluded that memory clinics, as
      specialized outpatient services, are concerned with research as well as clinical
      practice, and it is essentially this research which enables clinical practice to
      develop. 

PMID- 24927206
TI  - A possible clinical classification for the psychopathology of suicidal intent
      among psychiatric inpatients committing suicide.
AB  - Mental health professionals are poor at predicting suicides. A study of inpatient
      suicides over 21 years allowed an opportunity to develop a potentially useful
      clinical classification of the psychopathology of Suicidal intent. One hundred
      and three inpatient suicides in a large mental hospital were examined. Although
      case notes of 93 suicide patients were available for detailed examination, only
      33 case notes had sufficient data for classification of suicidal intent. Possible
      categories for classifying suicidal intent were developed, and four were
      identified: ambivalent, concealed, mixed and continuous. Evidence for the face
      validity of these concepts was provided by the clinical case-histories. The
      classification was reviewed in the context of the existing literature, which
      provided further evidence in support of its validity. This classification, if
      replicated, would be clinically helpful and might assist further improvement in
      the management of psychiatric inpatients. 

PMID- 24927207
TI  - Effective treatment of schizophrenia with quetiapine in a 34-year-old Caucasian
      man.
AB  - This case history reports on the sustained clinical efficacy of quetiapine in a
      34-year-old man with chronic paranoid schizophrenia, who was a partial responder
      to traditional therapy. Quetiapine was found to be effective against both
      positive and negative symptoms of schizophrenia, and had an excellent safety
      profile. The patient, who had also suffered from alcohol dependency, decreased
      his alcohol consumption as a result of responding to therapy, and successfully
      became re-integrated into society. 

PMID- 24927208
TI  - Paranoid psychosis in an 11-year-old boy following cardiac transplantation.
AB  - This is the first reported case of psychotic illness following pediatric cardiac
      transplantation. The case highlights diagnostic issues, and indicates a need for
      monitoring the psychological effects of cardiac transplantation in children. 

PMID- 24927209
TI  - Adjunctive use of olanzapine in the treatment of mania.
AB  - Olanzapine is an atypical antipsychotic which is licensed only for the treatment
      of schizophrenia. Two cases are described in which olanzapine was used (IS an
      adjunct to lithium in treating mania in patients with bipolar disorder. In both
      cases the lithium-olanzapine combination was more effective and better tolerated
      than a previous combination of lithium with a traditional antipsychotic.
      Olanzapine may offer significant advantages over traditional antipsychotics in
      the treatment of mania, but controlled trials are needed to confirm this. 

PMID- 24927210
TI  - Childhood hyperkinetic disorder/attention deficit disorder grown up.
AB  - There is growing evidence for the validity of the diagnosis of Attention Deficit
      Hyperkinetic Disorder (ADHD) in adults, as well as evidence that conduct disorder
      in adolescents and dissocial personality disorder in adult life are linked to
      ADHD in childhood. Methylphenidate is an effective treatment of ADHD in
      adolescents and young adults and it is possible that dissocial personality
      disorder will respond to methylphenidate. There is no evidence that
      methylphenidate reduces symptoms of conduct disorder in adolescents or of
      dissocial personality disorder in young adults, because no studies have evaluated
      methylphenidate in these conditions. We recorded a dramatic improvement in
      symptoms, predominantly of conduct disorder, in an adolescent with a previous
      history of ADHD. Trials of methylphenidate are required in adolescents with
      conduct disorder and young people with dissocial personality disorder, when there
      is a past history of probable ADHD. 

PMID- 24927211
TI  - Topics in contemporary psychiatric practice: Risk.

PMID- 24927214
TI  - Neutral color tuning of polymer electrochromic devices using an organic dye.
AB  - Herein, we present a facile, one-step method to color tune electrochromic devices
      (ECDs) that switch between two neutral colors via in situ electrochemical
      polymerization of electroactive monomers in the presence of a small molecule
      organic yellow dye using all commercially available materials. These devices
      exhibited photopic contrasts of ca. 30% without background correction when
      assembled on flexible PET-ITO substrates. In addition, devices exhibited
      switching speeds as low as 1 second, color uniformity, and stability. Large
      defect free ECDs of 100 cm(2) were fabricated exceeding the active switch area
      required for goggles, lenses, and small display applications. 

PMID- 24927215
TI  - First oxido-bridged cubo-octahedral hexanuclear rhenium clusters.
AB  - The first discrete hexanuclear metal clusters with cores adopting the M6(MU-O)12
      cubo-octahedral topology have been synthesized in the course of a simple one-pot
      reaction. We present a new class of rhenium clusters which are the first
      hexanuclear rhenium complexes with 12 bridging ligands and the first clusters
      with octahedrally arranged Re atoms bridged only by O atoms forming a unique cube
      like Re6(MU-O)12 unit. Our synthetic strategy demonstrates a new approach to the
      syntheses of polynuclear rhenium complexes under mild conditions. We discovered
      that the [Re6(MU-O)12(3-Mepy)6]BPh4 cluster compound has the ability to undergo
      reversible or/and quasireversible redox reactions without changing spatial
      structure and overall geometry. Subsequently, a reduction reaction of [Re6(MU
      O)12(3-Mepy)6]BPh4 was performed successfully and almost quantitatively resulting
      in the formation of the molecular [Re6(MU-O)12(3-Mepy)6] complex. 

PMID- 24927216
TI  - Bundled assembly of helical nanostructures in polymeric micelles loaded with
      platinum drugs enhancing therapeutic efficiency against pancreatic tumor.
AB  - Supramolecular assemblies of amphiphilic block copolymers having polypeptide
      segments offer significant advantages for tailoring spatial arrangement based on
      secondary structures in their optically active backbones. Here, we demonstrated
      the critical effect of alpha-helix bundles in cisplatin-conjugated poly(L- (or D
      )glutamate) [P(L(or D)Glu)-CDDP] segment on the packaging of poly(ethylene
      glycol) (PEG)-P(L(or D)Glu)-CDDP block copolymers in the core of polymeric
      micelles (CDDP/m) and enhanced micelle tolerability to harsh in vivo conditions
      for accomplishing appreciable antitumor efficacy against intractable pancreatic
      tumor by systemic injection. CDDP/m prepared from optically inactive PEG-poly(D,L
      glutamate) (P(D,LGlu)), gradually disintegrated in the bloodstream, resulting in
      increased accumulation in liver and spleen and reduced antitumor efficacy.
      Alternatively, CDDP/m from optically active PEG-P(L(or D)Glu) maintained micelle
      structure during circulation, and eventually attained selective tumor
      accumulation while reducing nonspecific distribution to liver and spleen.
      Circular dichroism and small-angle X-ray scattering measurements indicated
      regular bundled assembly of alpha-helices in the core of CDDP/m from PEG-P(L(or
      D)Glu), which is suggested to stabilize the micelle structure against dilution in
      physiological condition. CDDP/m suffered corrosion by chlorides in medium, yet
      the optically active micelles with alpha-helix bundles kept the micelle structure
      for prolonged time, with slowly releasing unimers and dimers from the surface of
      the bundled core in an erosion-like process, as verified by ultracentrifugation
      analysis. This is in sharp contrast with the abrupt disintegration of CDDP/m from
      PEG-P(D,LGlu) without secondary structures. The tailored assembly in the core of
      the polymeric micelles through regular arrangement of constituting segments is
      key to overcome their undesirable disintegration in bloodstream, thereby
      achieving efficient delivery of loaded drugs into target tissues.

PMID- 24927217
TI  - The PI3K/mTOR dual inhibitor NVP-BEZ235 reduces the growth of ovarian clear cell
      carcinoma.
AB  - Patients with clear cell carcinoma of the ovary (OCCC) have poor survival due to
      resistance to standard chemotherapy. OCCC has frequent activating mutations of
      the PIK3CA gene. The present study was conducted to clarify the efficacy of the
      inhibition of the PI3K-AKT-mTOR pathway in OCCC. We used 8 OCCC cell lines and 5
      ovarian serous adenocarcinoma (OSAC) cell lines. The mutation status of the
      PIK3CA and KRAS genes was examined by direct sequencing. The IC50 values of NVP
      BEZ235 (BEZ235) and temsirolimus were determined by WST-8 assay. Protein
      expression levels of PI3K-AKT-mTOR pathway molecules were examined by western
      blotting. Cell cycle distribution was analyzed by flow cytometry. Annexin V
      staining was used for detecting apoptosis. We also investigated the effects of
      BEZ235 on OCCC tumor growth in a nude mouse xenograft model. Four of the 8 OCCC
      cell lines showed a PIK3CA mutation while none of the 5 OSAC cell lines showed a
      mutation. The IC50 values of BEZ235 for the OCCC cell lines were lower than these
      values for the OSAC cell lines. The IC50 value of temsirolimus was higher than
      BEZ235 in the OCCC cell lines. The PIK3CA mutation was more frequently noted in
      OCCC than OSAC cells, but the sensitivity of these cell lines to BEZ235 or
      temsirolimus was not related to the mutation status. pHER3 and pAkt proteins were
      expressed more frequently in OCCC compared with OSAC. However, protein expression
      levels were distributed widely, and were not related to the sensitivity.
      Treatment with BEZ235 suppressed expression of pAkt, although treatment with
      temsirolimus did not. OCCC cells exhibited G1 phase arrest after treatment with
      BEZ235 and apoptosis with a higher concentration of the agent. BEZ235
      significantly inhibited tumor growth in mice bearing OVISE and TU-OC-1 cell
      tumors. The present study indicated that the PI3K-AKT-mTOR pathway is a potential
      target for OCCC, and that BEZ235 warrants investigation as a therapeutic agent.

PMID- 24927218
TI  - Exploring ultrafast dynamics of pyrazine by time-resolved photoelectron imaging.
AB  - We present the simulation of time-resolved photoelectron imaging spectra of
      pyrazine in the gas phase. The approach we have adopted is based on the
      combination of the ab initio nonadiabatic molecular dynamics "on the fly" with an
      approximate treatment of the photoionization process using Dyson orbitals and
      Coulomb functions to describe the bound and ionized states of the photoelectron.
      The method has been implemented (Humeniuk, A.; et al. J. Chem. Phys 2013, 139,
      134104) in the framework of the time-dependent density functional theory and has
      been applied here to interrogate the ultrafast internal conversion between the S2
      and S1 states in pyrazine. Conventional time-resolved photoelectron spectra
      without angular resolution fail to locate the S2 -> S1 internal conversion,
      because the ionization potentials relevant for the photoionization channels S2 ->
      D1 (pi(-1)) and S1 -> D0 (n(-1)) are almost identical. Introducing the angular
      resolution in the photoelectron spectra reveals evidence of such ultrafast
      internal conversion and provides a more detailed picture of the overall dynamics.
      The simulated time- and energy-dependent anisotropy map obtained within the
      Dyson/time-dependent density functional theory approach is in good agreement with
      its experimental counterpart provided by Horio et al. (Horio, T.; et al. J. Am.
      Chem. Soc. 2009, 131, 10932). Our theoretical approach represents a general tool
      for mapping the time- and angle-resolved photoelectron spectra in complex systems
      and thus can be used to investigate the ultrafast relaxation processes occurring
      in isolated molecules. 

PMID- 24927219
TI  - Trianionic pincer and pincer-type metal complexes and catalysts.
AB  - Trianionic pincer and pincer-type ligands are the focus of this review. Metal
      ions from across the periodic table, from main group elements, transition metals,
      and the rare earths, are combined with trianionic pincer ligands to produce some
      of the most interesting complexes to appear in the literature over the past
      decade. This review provides a comprehensive examination of the synthesis,
      characterization, properties, and catalytic applications of trianionic pincer
      metal complexes. Some of the interesting applications employing trianionic pincer
      and pincer-type complexes include: (1) catalyzed aerobic oxidation, (2) alkene
      isomerization, (3) alkene and alkyne polymerization, (4) nitrene and carbene
      group transfer, (5) fundamental transformations such as oxygen-atom transfer, (6)
      nitrogen-atom transfer, (7) O2 activation, (8) C-H bond activation, (9) disulfide
      reduction, and (10) ligand centered storage of redox equivalents (i.e. redox
      active ligands). Expansion of the architecture, type of donor atoms, chelate ring
      size, and steric and electronic properties of trianionic pincer ligands has
      occurred rapidly over the past ten years. This review is structured according to
      the type of pincer donor atoms that bind to the metal ion. The type of donor
      atoms within trianionic pincer and pincer-type ligands to be discussed include:
      NCN(3-), OCO(3-), CCC(3-), redox active NNN(3-), NNN(3-), redox active ONO(3-),
      ONO(3-), and SNS(3-). Since this is the first review of trianionic pincer and
      pincer-type ligands, an emphasis is placed on providing the reader with in-depth
      discussion of synthetic methods, characterization data, and highlights of these
      complexes as catalysts. 

PMID- 24927220
TI  - Dimethylsilyl bis(amidinate)actinide complexes: synthesis and reactivity towards
      oxygen containing substrates.
AB  - The reactivity of the monoanionic amidinate ligand [(CH3)3CNC(Ph)NSiMe2NC(Ph)
      NHC(CH3)3]Li (1) with a silyl amido side arm towards the early actinides, uranium
      and thorium, was investigated. While the salt metathesis reaction with
      ThCl4(thf)3 afforded the bis(amidinate)thorium(iv) dichloride complex
      [(CH3)3CNC(Ph)NSi(CH3)2NC(Ph)-NHC(CH3)3]ThCl2 (2) in high yield, the reaction of
      ligand 1 with UCl4 leads to a Lewis acid supported nucleophilic attack of an
      incoming ligand unit, yielding the trichloro uranium complex
      [(CH3)3CNC(Ph)Si(CH3)2-N(C(CH3)3)C(Ph)NSi(CH3)2NC(Ph)N-(C(CH3)3]UCl3 (4). The
      exposure of in situ formed complex 2 to wet THF solutions (<1% w of water), gave
      the mono(amidinate)Th(iv)(chloro)(bis-hydroxo) dimeric complex
      [(CH3)3CNC(Ph)NSiMe2NC(Ph)NHC(CH3)3Th(OH)2(Cl)]2.(3) as bright red needles,
      exhibiting extremely short Th-OH bond distances (1.741(5) A and 1.737(5) A). The
      reactivity of the thorium complex 2 in the ring opening polymerization (ROP) was
      studied, showing high activity. Thermodynamic and kinetic measurements were
      performed to shed light on the mechanism for the ROP. 

PMID- 24927221
TI  - Surface asymmetry of coated spherical nanoparticles.
AB  - We validate the nonspherical grafting arrangement of isotropically coated
      spherical nanoparticles as very recently proposed. We utilize localized surface
      plasmon resonance enhanced dynamic polarized and depolarized light scattering
      from Au nanoparticles, the spherical symmetry of which was revealed by single
      particle dark-field spectroscopy. The same Au nanospheres are grafted with
      ligands of different chemistry and length. The wavelength dependent
      depolarization ratio and the two transport coefficients of these nanoparticles,
      obtained from the dynamic light scattering experiment, can only be reconciled
      with the TEM data, the single UV/vis extinction spectrum, and the dark-field
      spectroscopy experiments if their coating is described as asymmetric. Spatially
      anisotropic graft distribution on spherical nanoparticles impacts their assembly
      and understanding its origin will help control the structure and properties of
      polymer nanocomposites. 

PMID- 24927222
TI  - A novel 2-step culture model for long-term in vitro maintenance of human
      pancreatic acinar cells.
AB  - OBJECTIVES: Because of rapid loss of functional differentiation that regularly
      occurs in vitro, culture systems permitting long-term studies on pancreatic
      acinar cells pose a major technical challenge. We recently described a method for
      long-term cultivation of mouse acinar cells. Here, we introduce a novel 2-step
      culture system for human pancreatic acinar cells. METHODS: The system involves 2
      successive culture phases, which are as follows: primary organotypic culture of
      isolated acinar clusters under soft Matrigel (BD Biosciences, Bedford, Mass;
      range, 2-3 days) followed by dissociation and secondary monolayer culture of
      acinar cells (4 days). Basal and agonist-induced amylase secretion was used to
      assess the secretory capability. RESULTS: Acinar clusters showed excellent
      morphology and stable basal amylase secretion throughout primary culture.
      Carbachol (0.1 mM/L) increased amylase secretion 1.4-fold (P = 0.021) versus
      basal in 3 independent 4-day secondary cultures. Despite the controversy about
      the presence and roles of cholecystokinin receptors in human acinar cells, one of
      them also responded to 0.1 and 10 nM/L concentrations of caerulein with 1.9- and
      1.4-fold increases in the rate of amylase secretion, respectively. CONCLUSIONS:
      Our technique allows cultured human acinar cells to maintain secretory
      differentiation for a minimum of 7 days. The technique provides novel prospects
      for in vitro modeling of the human exocrine pancreas.

PMID- 24927223
TI  - Porphodilactones as synthetic chlorophylls: relative orientation of beta
      substituents on a pyrrolic ring tunes NIR absorption.
AB  - Porphodilactones represent the porphyrin analogues, in which the peripheral bonds
      of two pyrrole rings are replaced by lactone moieties. They provide an
      opportunity to investigate how beta-substituent orientation of porphyrinoids
      modulates the electronic structures and optical properties, in a manner similar
      to what is observed with naturally occurring chlorophylls. In this work, a
      comprehensive description of the synthesis, characterization, and optical
      properties of meso-tetrakispentafluorophenylporphodilactone isomers is first
      reported. The beta-dilactone moieties are found to lie at opposite pyrrole
      positions (trans- and cis-configurations are defined by the relative orientations
      of the carbonyl group when one lactone moiety is fixed), in accordance with
      earlier computational predictions (Gouterman, M. J. Am. Chem. Soc. 1989, 111,
      3702). The relative orientation of the beta-dilactone moieties has a significant
      influence on the electronic structures and photophysical properties. For example,
      the Qy band of trans-porphodilactone is red-shifted by 19 nm relative to that of
      the cis-isomer, and there is a 2-fold increase in the absorption intensity, which
      resembles the similar trends that have been reported for natural chlorophyll f
      and d. An in depth analysis of magnetic circular dichroism spectral data and TD
      DFT calculations at the B3LYP/6-31G(d) level of theory demonstrates that the
      trans- and cis-orientations of the dilactone moieties have a significant effect
      on the relative energies of the frontier pi-molecular orbitals. Importantly, the
      biological behaviors of the isomers reveal their different photocytotoxicity in
      NIR region (>650 nm). The influence of the relative orientation of the beta
      substituents on the optical properties in this context provides new insights into
      the electronic structures of porphyrinoids which could prove useful during the
      development of near-infrared absorbing photosensitizers. 

PMID- 24927224
TI  - Learning curve for endoscopic submucosal dissection of gastric submucosal tumors:
      is it more difficult than it may seem?
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD), as a minimally invasive
      technique, is gaining wide acceptance for treating epithelial neoplasms. More
      recently, some pioneers have developed ESD for the treatment of submucosal tumors
      (SMTs), but characterization of the learning curve is lacking. In this study we
      aimed to evaluate the learning curve for ESD of gastric SMTs. SUBJECTS AND
      METHODS: From September 2008 to April 2011, ESD was performed in 50 consecutive
      patients with gastric SMTs by a single experienced endoscopist at our high-volume
      institution. The cumulative sum (CUSUM) method was performed to analyze the
      shifts in operative time (OT) and consequently to investigate the learning curve.
      RESULTS: Analysis of the OT using the CUSUM method identified two distinct
      phases: Phase 1 (the initial 32 cases) and Phase 2 (the remaining 18 cases).
      Phase 1 represented the initial learning period, whereas Phase 2 showed the more
      skilled and higher proficiency period, with a significant reduction in OT (90+/
      29 minutes versus 55+/-20 minutes; P<.0001). The two phases did not differ
      significantly with respect to patient characteristics and other perioperative
      parameters. CONCLUSIONS: Mastery of operative technique for ESD of SMTs is
      evident by a decrease in OT identified by CUSUM graphs. For endoscopists
      competent in basic endoscopic intervention skills, the learning curve should be
      achieved after approximately 32 cases. Offering this minimally invasive
      endoscopic intervention does not result in increased complication rate even in
      the early phase of the learning curve.

PMID- 24927225
TI  - The effect of out-of-home activity intervention delivered by volunteers on
      depressive symptoms among older people with severe mobility limitations: a
      randomized controlled trial.
AB  - OBJECTIVES: To examine the effects of an individualized outdoor activity
      intervention carried out by volunteers on depressive symptoms among community
      living older people with severe mobility limitations who have difficulties
      accessing the outdoors independently. METHODS: Secondary analyses of the
      'Volunteering, Access to Outdoor Activities and Wellbeing in Older People' (VOW)
      data (ISRCTN56847832). VOW was a randomized single blinded two-arm controlled
      trial conducted in Jyvaskyla, Finland, in 2009-2011. At baseline, 121 people aged
      67-92 years with severe mobility limitations were interviewed at home and
      randomized into either an intervention or waiting list control group. Volunteers
      (n = 47) had retired from regular work and were trained for the study. A
      volunteer assisted the participant in attending recreational out-of-home
      activities once a week for three months. Depressive symptoms were assessed using
      the Center for the Epidemiological Studies Depression Scale (CES-D). RESULTS: In
      the intervention group the CES-D score did not change during the intervention
      (from 15.1 +/- standard error 0.9 to 15.1 +/- 0.9), while in the control group it
      increased from 17.0 +/- 1.3 to 19.1 +/- 1.4 (intervention effect p = .096). Among
      the subgroups with minor depressive symptoms at baseline (CES-D score 16-20), the
      CES-D score decreased in the intervention group and increased in the control
      group (p = .025). CONCLUSION: A three-month outdoor activity intervention may
      improve mood among older people with severe mobility limitations. More randomized
      controlled trials of the topic are needed.

PMID- 24927226
TI  - Improved light absorption and charge transport for perovskite solar cells with
      rough interfaces by sequential deposition.
AB  - Recently, highly efficient solar cells based on organic-inorganic perovskites
      have been intensively reported for developing fabricating methods and device
      structures. Additional power conversion efficiency should be gained without
      increasing the thickness and the complexity of the devices to accord with
      practical applications. In this paper, a rough interface between perovskite and
      HTM was fabricated in perovskite solar cells to enhance the light scattering
      effect and improve the charge transport. The parameters related to the morphology
      have been systematically investigated by sequential deposition. Simultaneous
      enhancements of short-circuit current and power conversion efficiency were
      observed in both CH3NH3PbI3 and CH3NH3PbI3-xClx devices containing the rough
      interface, with power conversion efficiencies of 10.2% and 10.8%, respectively.
      Our finding provides an efficient and universal way to control the morphology and
      further optimize perovskite solar cells for devices by sequential deposition with
      various structures.

PMID- 24927228
TI  - Templated homoepitaxial growth with atomic layer deposition of single-crystal
      anatase (101) and rutile (110) TiO2.
AB  - Homoepitaxial growth of highly ordered and pure layers of rutile on rutile
      crystal substrates and anatase on anatase crystal substrates using atomic layer
      deposition (ALD) is reported. The epilayers grow in a layer-by-layer fashion at
      low deposition temperatures but are still not well ordered on rutile. Subsequent
      annealing at higher temperatures produces highly ordered, terraced rutile
      surfaces that in many cases have fewer electrically active defects than the
      substrate crystal. The anatase epitaxial layers, grown at 250  degrees C, have
      much fewer electrically active defects than the rather impure bulk crystals.
      Annealing the epilayers at higher temperatures increased band gap photocurrents
      in both anatase and rutile. 

PMID- 24927227
TI  - Quinone and hydroquinone metabolites from the ascidians of the genus Aplidium.
AB  - Ascidians of the genus Aplidium are recognized as an important source of chemical
      diversity and bioactive natural products. Among the compounds produced by this
      genus are non-nitrogenous metabolites, mainly prenylated quinones and
      hydroquinones. This review discusses the isolation, structural elucidation, and
      biological activities of quinones, hydroquinones, rossinones, longithorones,
      longithorols, floresolides, scabellones, conicaquinones, aplidinones,
      thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral
      data of these compounds is also presented. 

PMID- 24927229
TI  - Silencing of hypoxia-inducible adrenomedullin using RNA interference attenuates
      hepatocellular carcinoma cell growth in vivo.
AB  - Adrenomedullin (ADM) is an angiogenic peptide that has been shown to increase the
      risk of endometrial hyperplasia and to promote tumor cell survival following
      hypoxia. ADM may induce microvessel proliferation and partially decrease hypoxia
      in solid tumors, thus contributing to the proliferation of tumor cells, as well
      as tumor invasion and metastasis. However, the impact of hypoxia-induced ADM
      expression on hepatocellular carcinoma (HCC) cells requires further elucidation.
      In the present study it was found that the levels of ADM mRNA in tumor tissue
      from patients with HCC were significantly increased compared with the mRNA levels
      in adjacent non-tumorous liver tissue. Under hypoxic conditions, the mRNA and
      protein levels of ADM, as well as those of the cancer-promoting genes vascular
      endothelial growth factor and hypoxia-inducible factor 1alpha, were significantly
      elevated in a time-dependent manner in three human HCC cell lines. In addition,
      knockdown of ADM expression using short hairpin RNA (shRNA) in SMMC-7721 cells
      resulted in apoptosis that was not observed in untransfected cells. Furthermore,
      combined treatment with cisplatin and ADM-shRNA significantly decreased tumor
      growth in vivo compared with treatment with cisplatin or ADM-shRNA alone. These
      data demonstrate that ADM acts as a critical promoter of cell cycle progression
      in HCC and that the inhibition of ADM may be an effective interventional
      therapeutic strategy in HCC.

PMID- 24927230
TI  - Convergent approach to the tetracyclic core of the apparicine class of indole
      alkaloids via a key intermolecular nitrosoalkene conjugate addition.
AB  - Readily available methyl 3-formylindol-2-ylacetate and N-tosyl-4-chloro-3
      piperidone oxime have been used to construct the tetracyclic skeleton of the
      apparicine class of monoterpene indole alkaloids in only four steps in 80%
      overall yield. Key transformations in this convergent approach involve use of an
      intermolecular ester enolate/nitrosoalkene conjugate addition to form the C-15/16
      bond, followed by a reductive cyclization to construct the C-ring of the
      tetracycle. 

PMID- 24927231
TI  - Binding properties of herbicide chlorpropham to DNA: spectroscopic, chemometrics
      and modeling investigations.
AB  - The binding properties of chlorpropham (CIPC) to calf thymus DNA (ctDNA) were
      investigated in vitro by UV-vis absorption, fluorescence, circular dichroism (CD)
      and Fourier transform infrared (FT-IR) spectroscopy coupled with molecular
      modeling method. The results obtained from UV-vis absorption, fluorescence and CD
      spectroscopic methods as well as DNA viscosity and melting measurements indicated
      that the binding of CIPC to ctDNA was an intercalative mode. The FT-IR analysis
      and molecular modeling showed that CIPC mainly bound to guanine base of ctDNA.
      The association constant of the ctDNA-CIPC complex was determined to be in the
      order of 10(4) L mol(-1) by fluorescence titration. The calculated enthalpy
      change and entropy change suggested that hydrophobic forces and hydrogen bonds
      played prominent roles in the binding process. Furthermore, multivariate curve
      resolution-alternating least squares (MCR-ALS) approach was used to analyze the
      combined UV-vis absorption data matrix from the CIPC-ctDNA reaction system. The
      concentration profiles of the reaction components (CIPC, ctDNA and CIPC-ctDNA
      complex) and their pure spectra were successfully obtained to monitor the process
      of CIPC interaction with ctDNA. This study may contribute to the understanding of
      the CIPC-ctDNA interaction mechanism and toxicological effect of CIPC at the
      molecular level.

PMID- 24927232
TI  - Effect of a combination of green and blue monochromatic light on broiler immune
      response.
AB  - Our previous study suggested that green light or blue light would enhance the
      broiler immune response; this study was conducted to evaluate whether a
      combination of green and blue monochromatic light would result in improved immune
      response. A total of 192 Arbor Acre male broilers were exposed to white light,
      red light, green light, and blue light from 0 to 26 days. From 27 to 49 days,
      half of the broilers in green light and blue light were switched to blue light (G
      B) and green light (B-G), respectively. The levels of anti-Newcastle disease
      virus (NDV) and anti-bovine serum albumin (BSA) IgG in G-B group were elevated by
      11.9-40.3% and 17.4-48.7%, respectively, compared to single monochromatic lights
      (P<0.05). Moreover, the proliferation of peripheral blood T and B lymphocytes and
      the IL-2 concentration in the G-B groups increased by 10.4-36.2%, 10.0-50.0% and
      24.7-60.3% (P<0.05), respectively, compared with the single monochromatic light
      groups. However, the serum TNF-alpha concentration in the G-B group was reduced
      by 3.64-40.5% compared to other groups, and no significant difference was found
      between the G-B and B-G groups in any type of detection index at the end of the
      experiment. These results suggested that the combination of G-B and B-G
      monochromatic light could effectively enhance the antibody titer, the
      proliferation index of lymphocytes and alleviate the stress response in broilers.
      Therefore, the combination of green and blue monochromatic light can improve the
      immune function of broilers.

PMID- 24927233
TI  - Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative
      stress in hairless mice and exhibits antioxidant activity in vitro.
AB  - Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation
      dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is
      an antioxidant and inhibits nuclear factor-kappaB (NF-kappaB) activation. In the
      present study, the mechanisms of PDTC were investigated in cell free
      oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB
      induced NFkappaB activation in keratinocytes. PDTC presented the ability to
      scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS),
      2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also
      efficiently inhibited iron-dependent and -independent lipid peroxidation as well
      as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced
      skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory
      cytokine interleukin-1beta (IL-1beta), matrix metalloproteinase-9 (MMP-9),
      increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin
      tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also
      reduced UVB-induced IkappaB degradation in keratinocytes. These results
      demonstrate that PDTC presents antioxidant and anti-inflammatory effects in
      vitro, which line up well with the PDTC inhibition of UVB irradiation-induced
      skin inflammation and oxidative stress in mice. These data suggest that treatment
      with PDTC may be a promising approach to reduce UVB irradiation-induced skin
      damages and merits further pre-clinical and clinical studies. 

PMID- 24927235
TI  - Isolation of monovalent quantum dot-nucleic acid conjugates using magnetic beads.
AB  - Control of the valency that is achieved in the decoration of quantum dots (QDs)
      remains a challenge due to the high surface area of nanoparticles. A population
      distribution of conjugates is formed even when reactions involve use of one-to
      one molar equivalents of the ligand and QD. Monovalent conjugates are of
      particular interest to enable the preparation of multinanoparticle constructs
      that afford improved analytical functionality. Herein, a facile method for the
      formation and purification of QD-DNA monoconjugates (i.e., 1 DNA per QD) is
      described. Using diethylaminoethyl (DEAE) functionalized magnetic beads, a
      protocol was developed and optimized to selectively isolate QD-DNA monoconjugates
      from a mixture. Monoconjugates prepared with oligonucleotides as short as 19
      bases and as long as 36 bases were successfully isolated. The monoconjugates were
      isolated in less than 5 min with isolation efficiencies between 68% and 93%,
      depending on the length of oligonucleotide that was used. The versatility of the
      method was demonstrated by purifying monoconjugates prepared from commercially
      available, water-soluble QDs. The isolation of monoconjugates was confirmed using
      agarose gel electrophoresis and single molecule fluorescence spectroscopy.
      Examples are provided comparing the analytical performance of monoconjugates to
      collections of nanoparticles of mixed valencies, indicating the significance of
      this separation method to prepare nanomaterials for bioassay design. 

PMID- 24927236
TI  - PCR-RFLP detection of point mutations A2143G and A2142G in 23S rRNA gene
      conferring resistance to clarithromycin in Helicobacter pylori strains.
AB  - BACKGROUND: The occurrence of clarithromycin resistance among Helicobacter pylori
      strains is a major cause of the treatment failure. Resistance to this drug is
      conferred by point mutations in 23S rRNA gene and the most prevalent mutations
      are A2143G and A2142G. The aim of the study was to evaluate the occurrence of
      A2143G and A2142G mutations in a group of H. pylori strains resistant to
      clarithromycin. MATERIALS AND METHODS: The study included 21 clarithromycin
      resistant H. pylori strains collected between 2006 and 2009 in southern Poland.
      Resistance to clarithromycin was quantitatively tested with the E-test to
      determine the minimal inhibitory concentration (MIC value). The point mutations
      of H. pylori isolates were detected by PCR followed by RFLP analysis. RESULTS:
      The MIC values for clarithromycin for the analyzed strains ranged from 1.5 mg/L
      to 64 mg/L. Nine H. pylori strains exhibited A2143G mutation and A2142G mutation
      was found in 9 isolates as well. The results of RFLP analysis of 3 clarithromycin
      resistant strains were negative for both mutations. The average MIC values for
      A2143G and A2142G mutants were 6 and 30 mg/L, respectively. CONCLUSIONS:
      Frequencies of A2143G and A2142G mutations were the same in all isolates tested.
      Strains with A2143G mutation exhibited lower MIC values than A2142G mutants.
      Application of PCR-RFLP method for detection of clarithromycin resistance allows
      for better and more efficient management of H. pylori infections.

PMID- 24927237
TI  - Application of molecular techniques for the assessment of microorganism diversity
      on cultural heritage objects.
AB  - As a result of their unpredictable ability to adapt to varying environmental
      conditions, microorganisms inhabit different types of biological niches on Earth.
      Owing to the key role of microorganisms in many biogeochemical processes, trends
      in modern microbiology emphasize the need to know and understand the structure
      and function of complex microbial communities. This is particularly important if
      the strategy relates to microbial communities that cause biodeterioration of
      materials that constitute our cultural heritage. Until recently, the detection
      and identification of microorganisms inhabiting objects of cultural value was
      based only on cultivation-dependent methods. In spite of many advantages, these
      methods provide limited information because they identify only viable organisms
      capable of growth under standard laboratory conditions. However, in order to
      carry out proper conservation and renovation, it is necessary to know the
      complete composition of microbial communities and their activity. This paper
      presents and characterizes modern techniques such as genetic fingerprinting and
      clone library construction for the assessment of microbial diversity based on
      molecular biology. Molecular methods represent a favourable alternative to
      culture-dependent methods and make it possible to assess the biodiversity of
      microorganisms inhabiting technical materials and cultural heritage objects. 

PMID- 24927234
TI  - Clinical mechanism of the cystic fibrosis transmembrane conductance regulator
      potentiator ivacaftor in G551D-mediated cystic fibrosis.
AB  - RATIONALE: Ivacaftor is a cystic fibrosis transmembrane conductance regulator
      (CFTR) potentiator recently approved for patients with CF age 6 and older with
      the G551D mutation. OBJECTIVES: To evaluate ivacaftor in a postapproval setting
      and determine mechanism of action and response of clinically relevant markers.
      METHODS: We conducted a longitudinal cohort study in 2012-2013 in G551D CF
      patients age 6 and older with no prior exposure to ivacaftor. Study assessments
      were performed at baseline, 1, 3, and 6 months after ivacaftor initiation.
      Substudies evaluated mucociliary clearance, beta-adrenergic sweat secretion rate,
      gastrointestinal pH, and sputum inflammation and microbiology Measurements and
      Main Results: A total of 151 of 153 subjects were prescribed ivacaftor and 88%
      completed the study through 6 months. FEV1 % predicted improved from baseline to
      6 months (mean absolute change, 6.7%; P < 0.001). Similarly, body mass index
      improved from baseline to 6 months (mean change, 0.8 kg/m(2); P < 0.001). Sweat
      chloride decreased from baseline to 6 months (mean change, -53.8 mmol/L; 95%
      confidence interval, -57.7 to -49.9; P < 0.001), reflecting augmented CFTR
      function. There was significant improvement in hospitalization rate (P < 0.001)
      and Pseudomonas aeruginosa burden (P < 0.01). Significant improvements in
      mucociliary clearance (P < 0.001), gastrointestinal pH (P = 0.001), and
      microbiome were also observed, providing clinical mechanisms underlying the
      therapeutic benefit of ivacaftor. CONCLUSIONS: Significant clinical and
      physiologic improvements were observed on initiation of ivacaftor in a broad
      patient population, including reduced infection with P. aeruginosa. Biomarker
      studies substantially improve the understanding of the mechanistic consequences
      of CFTR modulation on pulmonary and gastrointestinal physiology.

PMID- 24927238
TI  - SpaCBA sequence instability and its relationship to the adhesion efficiency of
      Lactobacillus casei group isolates to Caco-2 cells.
AB  - The ability to adhere to enterocytes is one of the key features of probiotics.
      This process involves a number of factors, among which the important role of pili
      was demonstrated. Some Lactobacillus species are confirmed to have heterotrimeric
      spaCBA type pili. The aim of this study was to identify spaCBA pili in strains of
      selected Lactobacillus spp. and assess the impact of their presence and sequence
      polymorphism on the adhesion of these strains to enterocytes. Total 20 bacterial
      strains of L. rhamnosus, L. casei and L. paracasei were tested. The presence of
      pilus specific proteins coding genes spaA, spaB and spaC was verified by PCR in
      order to identify the presence of sequence polymorphism in the genes possibly
      affecting the structure of the spaCBA pilus. To correlate spaCBA polymorphism to
      adhesion capability the adhesion assay was carried out using Caco-2 cell line.
      The effectiveness of the adhesion was measured using a scintillation counter. The
      Lactobacillus strains analyzed showed the adhesion to Caco-2 enterocytes
      capability from 0.6% to 19.6%. The presence of spaCBA pili is a factor increasing
      the adhesion efficiency of Lactobacillus spp. to Caco-2 enterocytes. Lack of
      these structures on the surface of bacterial cells results in the reduction in
      adhesion efficiency, indicating its important role in the adhesion process. But
      not in all cases the correlation between the presence of protein spaCBA
      structures and adhesion efficiency was observed, what may indicate the important
      role of other factors in adhesion of analyzed strains to Caco-2 cells. 

PMID- 24927239
TI  - FDG-PET and amyloid-PET imaging: the diverging paths.
AB  - PURPOSE OF REVIEW: The availability of PET neuroimaging tools for the in-vivo
      assessment of metabolic dysfunction and amyloid burden in Alzheimer's disease has
      opened important methodological and practical issues in the diagnostic design and
      the conduct of new clinical trials. This review, addressing the different
      molecular information that the amyloid-PET and fluorodeoxyglucose-PET (FDG-PET)
      tools can provide, highlights their diverging paths in Alzheimer's disease and
      possible new perspectives in research and clinical applications. RECENT FINDINGS:
      Senile plaques and neurofibrillary tangles are prominent neuropathological
      hallmarks in Alzheimer's disease and are considered to be targets for therapeutic
      intervention and biomarkers for diagnostic in-vivo imaging agents. Alzheimer's
      disease is a slowly progressing disorder, in which pathophysiological
      abnormalities, detectable in vivo by PET biomarkers, precede clinical symptoms by
      many years to decades. The unitary view of Alzheimer's disease as a sequential
      pathological pathway, with beta-amyloid (Abeta) as the only initial and causal
      event (the 'amyloid cascade hypothesis'), is likely to be progressively replaced
      by a more complex picture, also on the basis of recent PET imaging findings
      showing that neuronal injury biomarkers and tau pathology can be independent of
      beta-amyloid deposition. SUMMARY: The different molecular paths that PET in-vivo
      biomarkers can reveal in the timeframe of Alzheimer's disease progression reflect
      the events leading to deposition of Abeta and phosphorylated tau, neuronal injury
      and neurodegeneration, which can run in parallel instead of in a sequential
      manner. The amyloid and neuronal injury paths may diverge along the Alzheimer's
      disease cascade and bear separate relationships with Alzheimer's disease symptoms
      and clinical phenotypes. All these evidences are crucial for the diagnosis and
      the development of new drugs aimed at slowing or preventing dementia.

PMID- 24927240
TI  - Examining the media portrayal of obesity through the lens of the Common Sense
      Model of Illness Representations.
AB  - This study examined the Irish media discourse on obesity by employing the Common
      Sense Model of Illness Representations. A media sample of 368 transcripts was
      compiled from newspaper articles (n = 346), radio discussions (n = 5), and online
      news articles (n = 17) on overweight and obesity from the years 2005, 2007, and
      2009. Using the Common Sense Model and framing theory to guide the investigation,
      a thematic analysis was conducted on the media sample. Analysis revealed that the
      behavioral dimensions of diet and activity levels were the most commonly cited
      causes of and interventions in obesity. The advertising industry was blamed for
      obesity, and there were calls for increased government action to tackle the
      issue. Physical illness and psychological consequences of obesity were prevalent
      in the sample, and analysis revealed that the economy, regardless of its state,
      was blamed for obesity. These results are discussed in terms of expectations of
      audience understandings of the issue and the implications of these dominant
      portrayals and framings on public support for interventions. The article also
      outlines the value of a qualitative analytical framework that combines the Common
      Sense Model and framing theory in the investigation of illness narratives. 

PMID- 24927241
TI  - Age-related difference in relationships between cognitive processing speed and
      general cognitive status.
AB  - General cognitive status (GCS) is a composite of cognitive abilities reflecting
      full function. The literature suggests a relationship between cognitive
      processing speed and GCS, as well as age-related changes of processing speed on
      cognitive performance. Therefore, this study recruited 34 younger and 39 older
      adults to verify age-related differences in relationships between cognitive
      processing speed and GCS. We measured cognitive processing speed with the
      Processing Speed Index of the Wechsler Adult Intelligence Scale. Findings
      indicated that cognitive processing speed predicted GCS in older but not younger
      adults. Future research may be needed to verify the training effect of processing
      speed on GCS. This study also further examined cognitive factors related to
      processing speed in aging and the relationships between cognitive processing
      speed and verbal fluency, cognitive inhibition, and divided attention. A stepwise
      regression analysis indicated that only verbal fluency contributed significantly
      to cognitive processing speed in older adults, accounting for 21% of the
      variance. These observations suggest that age-related changes of prefrontal
      regions may not fully explain age-related decline in cognitive processing speed. 

PMID- 24927242
TI  - Intensive upconversion luminescence of Na-codoped rare-earth oxides with a novel
      RE-Na heterometallic complex as precursor.
AB  - Four novel heterometallic RE-Na-organic frameworks, [(RE)Na3(PZTC)2(H2O)4].2H2O
      (RE = Yb (1), Ho (2), Er (3), Y (4); PZTC = pyrazine-2,3,5-tricarboxylate), were
      synthesized via solvothermal reactions and characterized by IR, elemental
      analysis, and single-crystal X-ray diffraction. The results show that the four
      complexes are isostructural. In the frameworks, the trinuclear Na cluster and RE
      ion acting as nodes are bridged by the multifunctional PZTC ligand to give a 3-D
      framework. Codoping in the frameworks was realized due to their isostructural
      characteristics. The codoped complexes were calcinated at 800  degrees C to give
      rise to the corresponding oxides. Investigation of their photophysical properties
      shows that the upconversion luminescence (UCL) of the Ho system is green while
      that of the Er system is red upon excitation at 980 nm. With regard to the
      luminescence color and intensity, the Er system is preferable to the Ho system
      for application in bioimaging. Both the red and the green UCL of the Ho(3+) and
      Er(3+) systems involve a two-photon process. In addition, the UCL mechanism is
      given. The UCL comparison of Na-doped oxides with non-Na-doped oxides indicates
      that doping Na can greatly enhance the UCL of the Er system. 

PMID- 24927243
TI  - Impaired nerve conduction velocity in MPTP-treated mouse model of Parkinson's
      disease.
AB  - Electrophysiological examination can provide valuable information on functional
      abnormalities in patients with Parkinson's disease (PD). Although there are
      numerous reports on biochemical and molecular alterations in 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced experimental parkinsonism in mice, the
      mode of electrophysiology in this animal model of PD is not clear. This study
      provides a comparative evaluation of corticomotor evoked potential (CMEP),
      compound muscle action potential (CMAP) and motor nerve conduction velocity (NCV)
      in mice treated with MPTP (30 mg/kg, ip, daily for 4 days) or saline (control
      group). Although the CMEP latencies were similar in both the groups, the CMEP
      amplitude was non-significantly decreased in MPTP-treated mice. There was a
      significant increase in the CMAP latency (1.37 +/- 0.03 versus 1.20 +/- 0.02 ms)
      and decrease in CMAP amplitude (4.50 +/- 0.89 versus 8.31 +/- 0.86 mV) in MPTP
      treated mice as compared with control group. This prolonged conduction time
      resulted in a significant decrease in NCV in MPTP-treated mice (21.98 +/- 0.54
      m/s) as compared with control mice (24.47 +/- 0.33 m/s). There was a significant
      depletion of striatal dopamine in MPTP-treated animals. These findings
      demonstrate that systemic administration of MPTP significantly impairs both the
      central and peripheral nervous systems in mice. However, the resemblance of this
      neurophysiological status with idiopathic PD or other animal models of PD is not
      clear and requires additional studies.

PMID- 24927244
TI  - Combination therapy utilizing ketamine and transcranial magnetic stimulation for
      treatment-resistant depression: a case report.
AB  - In the present article, we report on the case of a 23-year-old woman with a
      history of treatment-resistant depression who achieved significant symptom
      improvement with a novel treatment consisting of ketamine, a dissociative
      anesthetic, and external neuromodulation with transcranial magnetic stimulation
      (TMS). This case highlights the need for further investigation of treatments
      pairing external neuromodulation with dissociative anesthetics. 

PMID- 24927245
TI  - Comparing robotic surgery with conventional laparoscopy and laparotomy for
      cervical cancer management.
AB  - OBJECTIVE: The aim of this study was to compare the outcomes of robotic surgery,
      laparoscopy, and laparotomy for the surgical treatment of stage IA to IIB
      cervical cancer. METHODS: This retrospective study was carried out in a
      university-affiliated teaching hospital. A total of 100 women with an initial
      diagnosis of stage IA to IIB cervical cancer, without preoperative brachytherapy
      or chemotherapy, were included in this study. With selection of the cases, 44
      patients received laparotomy surgery, 32 patients received laparoscopic surgery,
      and 24 patients received robotic surgery. The perioperative parameters measured
      included operation time, blood loss, transfusion rate, lymph node yield, adhesion
      score, laparotomy conversion rate, postoperative and 24-hour pain scores, time to
      full diet resumption, and hospital stay. The perioperative complication and
      disease-free survival were also evaluated. RESULTS: The robotic group showed a
      shorter operation time, less blood loss, lower transfusion rate, and lower
      laparotomy conversion rate than the laparoscopic or laparotomy group. As for the
      postoperative parameters, the robotic group showed reduced postoperative and 24
      hour pain scores, shortened length of hospital stay, and decreased time to full
      diet resumption compared with the other 2 surgical groups. No significant
      differences were found between the groups in perioperative complication rate or
      disease-free survival. CONCLUSIONS: The data suggested that robotic surgery is a
      feasible and potentially optimal option for the treatment of stage IA to IIB
      cervical cancer with favorable short-term surgical outcomes.

PMID- 24927247
TI  - Impact of body mass index on surgical outcomes and analysis of disease recurrence
      for patients with endometrial cancer undergoing robotic-assisted staging.
AB  - OBJECTIVE: This study aimed to evaluate the impact of body mass index (BMI) on
      the short- and long-term outcomes of patients with endometrial cancer who
      underwent robotic-assisted staging and to analyze disease recurrence and
      recurrence-free survival (RFS). MATERIALS AND METHODS: The charts of all
      consecutive patients with endometrial cancer who underwent robotic surgery from
      March 2007 to October 2012 were analyzed. Patients with follow-up less than 12
      months after surgery were censored from the RFS analysis. RESULTS: Mean (SD) age
      for the 364 patients was 63.6 (10) years, and mean (SD) BMI was 34.8 (10.1) kg/m.
      Conversions were in 3 (0.8%) of 364 cases. The mean (SD) operative time was 162.3
      (54.6) minutes. Mean (SD) postoperative hospitalization was 1.6 (1.9) days.
      Histology included 80.5% endometrioid and 19.5% clear cell, serous, and
      carcinosarcomas. Mean (SD) pelvic and paraaortic lymph node counts were 15.9
      (8.2) and 3.6 (4.3), respectively. Metastatic disease was diagnosed in 58 (16%)
      of 364 patients. The median follow-up was 29.3 months. The recurrence rates were
      4.1% for the patients with endometrioid carcinoma and 14.1% for nonendometrioid
      histologies. Recurrences in patients with BMI less than 30 kg/m accounted for
      68.2% of all recurrences (15/22 patients). The rest of recurrences (7/22
      patients, 31.8%) were in obese patients. Moreover, when analyzed for each
      histologic subtype, recurrence rates were consistently higher for patients with
      BMI less than 30 kg/m when compared with patients with BMI greater than 30 kg/m.
      The 3-year overall survival was 98.2%, and the 3-year RFS was 92%. CONCLUSIONS:
      Obesity and morbid obesity did not affect adversely the operative outcomes for
      patients with endometrial cancer who were operated on using the robotic system.
      The recurrence rates were lower for patients with BMI greater than 30 kg/m
      compared with patients with BMI less than 30 kg/m for both endometrioid and
      nonendometrioid cancers.

PMID- 24927246
TI  - Quality of life, body mass index, and physical activity among uterine cancer
      patients.
AB  - OBJECTIVE: The purpose of this study was to assess the independent and joint
      effects of body mass index (BMI) and physical activity (PA) on overall quality of
      life (QoL) in survivors of uterine cancer. METHODS: We conducted a survey among
      uterine cancer patients who received curative therapy at the University of
      Pennsylvania between 2006 and 2010. Surveys assessed the weight, height, PA
      (college alumnus survey), and QoL (Functional Assessment of Cancer Therapy
      Gynecologic Oncology Group). RESULTS: The response rate to the survey was 43%.
      Among 213 patients, the mean (SD) BMI was 31.1 (8.9) kg/m, and 48% reported
      greater than or equal to 150 min.wk of PA. Higher BMI was independently
      associated with poorer overall QoL (P = 0.050), including physical (P = 0.002)
      and functional well-being (P = 0.008). Higher min.wk of PA was not independently
      associated with any QoL outcome. However, among patients who engaged in greater
      than or equal to 150 min.wk of PA, the negative association between BMI and
      overall QoL was attenuated (P = 0.558), whereas among patients who engaged in
      less than 150 min.wk of PA, the negative association between BMI and overall QoL
      persisted (P = 0.025). Among patients who engaged in greater than or equal to 150
      min.wk of PA, the negative association between BMI and physical and functional
      well-being was attenuated (P = 0.765 and P = 0.284), whereas among patients who
      engaged in less than 150 min.wk of PA, the negative association between BMI and
      physical and functional well-being persisted (P < 0.001 and P = 0.010),
      respectively. CONCLUSIONS: Body mass index is associated with poorer QoL among
      uterine cancer patients. The findings from this cross-sectional study are
      consistent with the hypothesis that endometrial cancer survivors who are able to
      perform 150 min/wk of PA may be protected from the negative effects of BMI on
      QoL.

PMID- 24927248
TI  - Preoperative ultrasound-guided needle biopsy of 63 uterine tumors having high
      signal intensity upon T2-weighted magnetic resonance imaging.
AB  - OBJECTIVE: The differential diagnosis between uterine sarcoma and benign
      leiomyoma is difficult when made only by magnetic resonance imaging (MRI); it
      usually requires an additional preoperative diagnostic procedure. We report our
      results using ultrasound-guided needle biopsy for these types of uterine tumors.
      METHODS: Ultrasound-guided needle biopsy was performed on 63 patients with
      uterine smooth muscle tumors suspected of malignancy by MRI. We compared the
      results of presurgical biopsy against the postsurgical pathology of the tumor.
      RESULTS: Among 63 patients with a high signal intensity of the uterine tumor on
      T2-weighted MRI (1 case was undetermined), 12 cases (19.3%) were diagnosed by the
      needle biopsy as malignant, and 51 cases (80.6%) were benign. Among the 12
      diagnosed as malignant tumors, 11 had surgery performed, and one was treated with
      chemotherapy. Among the 51 patients diagnosed with a benign tumor, 27 had surgery
      performed, and 24 were put on a wait-and-see clinical follow-up schedule. One of
      the 27 surgical patients with a benign tumor had a postsurgical diagnosis of a
      low-grade endometrial stromal sarcoma. In the 38 cases where surgery was
      performed, we found the sensitivity, specificity, and the positive and negative
      predictive values of the needle biopsy were 91.7%, 100%, 100%, and 96.2%,
      respectively. CONCLUSIONS: Ultrasound-guided needle biopsy may be a reliable
      preoperative diagnostic procedure for uterine tumors with suspected malignancy.

PMID- 24927249
TI  - Sentinel lymph node detection using 99mTc combined with methylene blue cervical
      injection for endometrial cancer surgical management: a prospective study.
AB  - OBJECTIVE: The aim of this study is to evaluate the effectiveness of a combined
      technique for sentinel lymph node (SLN) localization and surgical staging of
      endometrial carcinoma. METHODS: This is a single-center prospective observational
      study carried out from September 2011 to December 2013 including women with a
      diagnosis of endometrial cancer and scheduled for surgery. A regional lymph node
      mapping was obtained using SPECT-CT (cervical injection of Tc) the day before
      surgery. On the day of surgery, methylene blue was injected in the cervical
      tissue. The SLNs were identified intraoperatively guided both by a gamma-probe
      and visual inspection of the blue dye. A pelvic and/or para-aortic
      lymphadenectomy was completed. A histological analysis was performed on all the
      removed lymph nodes. We calculated the detection rate for SLN and its negative
      predictive value (NPV) for malignancy. RESULTS: Fifty patients underwent surgery.
      The SLN was isolated in 46 patients with detection rate of 92% (95% confidence
      interval, 80.77-97.78). The mean number of detected SLNs per patient was 1.54
      (range, 1-5); the average number of non-SLNs removed was 17 (5-34) per patient.
      The most common SLN location was the external iliac lymph node chain, 33
      (46.47%). Five SLNs (7.1%) were isolated in the para-aortic chain. Three SLN
      cases (5.9%) were positive for malignant cells; the totality of the remaining non
      SLNs was negative. The NPV of the SLN was 100% (95% confidence interval, 89.79
      99.79). Finally, pathologic findings were 42 endometrioid types (84%), 3
      carcinosarcomas (6%), 4 clear cell (8%), and 1 serous papillary tumor (2%).
      CONCLUSIONS: The SLN analysis may be useful to assess the presence or absence of
      lymph node metastases. Its high NPV may be used as criteria to avoid unnecessary
      lymphadenectomies in endometrial cancer patients.

PMID- 24927250
TI  - New orally active dual enkephalinase inhibitors (DENKIs) for central and
      peripheral pain treatment.
AB  - Protecting enkephalins, endogenous opioid peptides released in response to
      nociceptive stimuli, is an innovative approach for acute and neuropathic pain
      alleviation. This is achieved by inhibition of their enzymatic degradation by two
      membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and
      aminopeptidase N (APN, EC 3.4.11.2). Selective and efficient inhibitors of both
      enzymes, designated enkephalinases, have been designed that markedly increase
      extracellular concentrations and half-lives of enkephalins, inducing potent
      antinociceptive effects. Several chemical families of Dual ENKephalinase
      Inhibitors (DENKIs) have previously been developed but devoid of oral activity.
      We report here the design and synthesis of new pro-drugs, derived from co-drugs
      combining a NEP and an APN inhibitor through a disulfide bond with side chains
      improving oral bioavailability. Their pharmacological properties were assessed in
      various animal models of pain targeting central and/or peripheral opioid systems.
      Considering its efficacy in acute and neuropathic pain, one of these new DENKIs,
      19-IIIa, was selected for clinical development. 

PMID- 24927251
TI  - Exploring mutasynthesis to increase structural diversity in the synthesis of
      highly oxygenated polyketide lactones.
AB  - The enantioselective synthesis of (2R,3R,4E,8E)-3-hydroxy-2,4,8-trimethyldeca-4,8
      dienolide (5) by ring-closing metathesis is described. This compound is an
      analogue of 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (4) which is a rare 11
      membered lactone produced by the fungus, Botrytis cinerea. Mutasynthetic studies
      with compound 5 using two mutants of B. cinerea led to the isolation of four new
      highly oxygenated 11-membered lactones (11-14) in which compound 5 has been
      stereoselectively epoxidized and hydroxylated at sites that were not easily
      accessible by classical synthetic chemistry. 

PMID- 24927252
TI  - Synergistic effects of ultrasound and sodium hypochlorite (NaOCl) on reducing
      Listeria monocytogenes ATCC19118 in broth, stainless steel, and iceberg lettuce.
AB  - This study was performed in order to determine whether a combined treatment of
      ultrasound and sodium hypochlorite (NaOCl) is more effective than individual
      treatment on reducing Listeria monocytogenes ATCC19118 on stainless steel and
      iceberg lettuce. The bactericidal effect of ultrasound and NaOCl was investigated
      in tryptic soy broth (TSB), on stainless steel and iceberg lettuce. Various
      concentrations of NaOCl (50, 100, 150, and 200 ppm) were tested along with
      various ultrasound treatment times (5, 20, 40, 60, 80, and 100 min). The combined
      treatment of ultrasound and NaOCl resulted in greater bacterial reductions than
      either treatment alone, without causing any significant changes in lettuce
      texture. The synergistic values of combined ultrasound and NaOCl treatments in
      TSB, on stainless steel, and on iceberg lettuce were 0.01-0.99 log10 colony
      forming units (CFU)/mL, 0.01-0.62 log 10 CFU/g, and 0.12-1.66 log10 CFU/g,
      respectively. These results suggest that the combination of ultrasound and NaOCl
      was more effective than each treatment against Listeria monocytogenes, and that
      this combination can effectively sanitize fresh products such as iceberg lettuce.

PMID- 24927253
TI  - Ad-endostatin treatment combined with low-dose irradiation in a murine lung
      cancer model.
AB  - Radiation therapy is a conventional strategy for treating advanced lung cancer
      yet is accompanied by serious side-effects. Its combination with other
      strategies, such as antiangiogenesis and gene therapy, has shown excellent
      prospects. As one of the potent endogenous vascular inhibitors, endostatin has
      been widely used in the antiangiogenic gene therapy of tumors. In the present
      study, LL/2 cells were infected with a recombinant adenovirus encoding endostatin
      (Ad-endostatin) to express endostatin. The results showed that LL/2 cells
      infected with the Ad-endostatin efficiently and longlastingly expressed
      endostatin. In order to further explore the role of Ad-endostatin combined with
      irradiation in the treatment of cancer, a murine lung cancer model was
      established and treated with Ad-endostatin combined with low-dose irradiation.
      The results showed that the combination treatment markedly inhibited tumor growth
      and metastasis, and prolonged the survival time of the tumor-bearing mice.
      Furthermore, this significant antitumor activity was associated with lower levels
      of microvessel density and anoxia factors in the Ad-Endo combined with
      irradiation group, and with an increased apoptotic index of tumor cells. In
      addition, no serious side-effects were noted in the combination group. Based on
      our findings, Ad-endostatin combined with low-dose irradiation may be a rational
      alternative treatment for lung cancer and other solid tumors. 

PMID- 24927255
TI  - A plutonium-based single-molecule magnet.
AB  - The magnetic properties of the 5f(5) [tris-(tri-1-pyrazolylborato)
      plutonium(III)] complex have been investigated by ac susceptibility measurements,
      showing it to be the first plutonium single-molecule magnet; its magnetic
      relaxation slows down with decreasing temperature through a thermally activated
      mechanism followed by a quantum tunnelling regime below 5 K.

PMID- 24927256
TI  - Direct osmolyte-macromolecule interactions confer entropic stability to folded
      states.
AB  - Protective osmolytes are chemical compounds that shift the protein
      folding/unfolding equilibrium toward the folded state under osmotic stresses. The
      most widely considered protection mechanism assumes that osmolytes are depleted
      from the protein's first solvation shell, leading to entropic stabilization of
      the folded state. However, recent theoretical and experimental studies suggest
      that protective osmolytes may directly interact with the macromolecule. As an
      exemplary and experimentally well-characterized system, we herein discuss poly(N
      isopropylacrylamide) (PNiPAM) in water whose folding/unfolding equilibrium shifts
      toward the folded state in the presence of urea. On the basis of molecular
      dynamics simulations of this specific system, we propose a new microscopic
      mechanism that explains how direct osmolyte-macromolecule interactions confer
      stability to folded states. We show that urea molecules preferentially accumulate
      in the first solvation shell of PNiPAM driven by attractive van der Waals
      dispersion forces with the hydrophobic isopropyl groups, leading to the formation
      of low entropy urea clouds. These clouds provide an entropic driving force for
      folding, resulting in preferential urea binding to the folded state and a
      decrease of the lower folding temperature in agreement with experiment. The
      simulations further indicate that thermodynamic nonideality of the bulk solvent
      opposes this driving force and may lead to denaturation, as illustrated by
      simulations of PNiPAM in aqueous solutions with dimethylurea. The proposed
      mechanism provides a new angle on relations between the properties of protecting
      and denaturing osmolytes, salting-in or salting-out effects, and solvent
      nonidealities. 

PMID- 24927257
TI  - On reproductive justice: 'domestic violence', rights and the law in India.
AB  - In this paper we draw attention to the difficulty of accessing reproductive
      rights in the absence of effective state and legal guarantees for gender equity
      and citizenship, and argue that if reproductive rights are to be meaningful
      interventions on the ground, they must be reframed in terms of reproductive
      justice. Drawing on multi-sited ethnographic fieldwork conducted in Rajasthan,
      Northwest India, we track two dynamic legal aid interventions on reproductive
      health rights in India, concerned with domestic violence and maternal mortality
      respectively, that have sought to fill this existing gap between ineffective
      state policies and the rhetoric on reproductive rights. Through an analysis of
      these interventions, we propose that requirements of reproductive justice cannot
      be met through discrete or private, albeit creative legal initiatives, pursued by
      individuals or civil society organisations but must involve comprehensive
      policies as well as strategies and alliances between state, non-state,
      transnational organisations and progressive political groups. 

PMID- 24927258
TI  - Increased growth-inhibitory and cytotoxic activity of arsenic trioxide in head
      and neck carcinoma cells with functional p53 deficiency and resistance to EGFR
      blockade.
AB  - BACKGROUND AND PURPOSE: Mutations in the p53 gene are frequently observed in
      squamous cell carcinoma of the head and neck region (SCCHN) and have been
      associated with drug resistance. The potential of arsenic trioxide (ATO) for
      treatment of p53-deficient tumor cells and those with acquired resistance to
      cisplatin and cetuximab was determined. MATERIAL AND METHODS: In a panel of 10
      SCCHN cell lines expressing either wildtype p53, mutated p53 or which lacked p53
      by deletion the interference of p53 deficiency with the growth-inhibitory and
      radiosensitizing potential of ATO was determined. The causal relationship between
      p53 deficiency and ATO sensitivity was evaluated by reconstitution of wildtype
      p53 in p53-deficient SCCHN cells. Interference of ATO treatment with cell cycle,
      DNA repair and apoptosis and its efficacy in cells with acquired resistance to
      cisplatin and cetuximab was evaluated. RESULTS: Functional rather than structural
      defects in the p53 gene predisposed tumor cells to increased sensitivity to ATO.
      Reconstitution of wt p53 in p53-deficient SCCHN cells rendered them less
      sensitive to ATO treatment. Combination of ATO with irradiation inhibited
      clonogenic growth in an additive manner. The inhibitory effect of ATO in p53
      deficient tumor cells was mainly associated with DNA damage, G2/M arrest,
      upregulation of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)
      receptors and apoptosis. Increased activity of ATO was observed in cetuximab
      resistant SCCHN cells whereas cisplatin resistance was associated with cross
      resistance to ATO. CONCLUSIONS: Addition of ATO to treatment regimens for p53
      deficient SCCHN and tumor recurrence after cetuximab-containing regimens might
      represent an attractive strategy in SCCHN.

PMID- 24927259
TI  - The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm
      infants to improve neurodevelopmental outcome: a randomized controlled trial-
      BARTrial.
AB  - BACKGROUND AND OBJECTIVE: High bilirubin/albumin (B/A) ratios increase the risk
      of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition
      to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We
      aimed to assess whether the additional use of B/A ratios in the management of
      hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.
      METHODS: In a prospective, randomized controlled trial, 615 preterm infants of 32
      weeks' gestation or less were randomly assigned to treatment based on either B/A
      ratio and TSB thresholds (consensus-based), whichever threshold was crossed
      first, or on the TSB thresholds only. The primary outcome was neurodevelopment at
      18 to 24 months' corrected age as assessed with the Bayley Scales of Infant
      Development III by investigators unaware of treatment allocation. Secondary
      outcomes included complications of preterm birth and death. RESULTS: Composite
      motor (100 +/- 13 vs. 101 +/- 12) and cognitive (101 +/- 12 vs. 101 +/- 11)
      scores did not differ between the B/A ratio and TSB groups. Demographic
      characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes
      were similar. The rates of death and/or severe neurodevelopmental impairment for
      the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus
      1.4% (P = 0.62) for birth weights <= 1000 g and 1.8% versus 5.8% (P = 0.03) and
      4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g. CONCLUSIONS: The
      additional use of B/A ratio in the management of hyperbilirubinemia in preterm
      infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION:
      Controlled-Trials.com ISRCTN74465643.

PMID- 24927261
TI  - "There's a higher power, but He gave us a free will": socioeconomic status and
      the intersection of agency and fatalism in infertility.
AB  - Existing literature characterizes fatalism as a passive reaction to health in the
      face of powerlessness and constructs agency as a more activist perspective based
      in self-efficacy and control. Frequently studied together, researchers extol
      agency as the appropriate approach to decision-making around health, while
      discouraging fatalistic outlooks. Despite associating such beliefs with social
      classes-agency with high socioeconomic status (SES) groups and fatalism with low
      SES groups-there is little research that compares health beliefs across class
      groups. By examining the medicalized condition of infertility among women of both
      high and low SES, this study examines how social class shapes reactions to health
      and illness. Through 58 in-depth interviews with infertile women in the U.S., we
      reveal the complexity of fatalism and agency and the reasons behind that
      complexity. We first examine the commonalities among SES groups and their mutual
      use of fatalism. We then demonstrate the nuance and continuity between the health
      beliefs themselves-fatalism can be agentic and agency can be achieved through
      fatalism. In other words, we disrupt the binary construction of health beliefs,
      their conflation with social class, and the static application of health beliefs
      as psychological attributes, ultimately exposing the classist basis of the
      concepts. Doing so can result in improved patient care and reduced health
      inequalities. 

PMID- 24927262
TI  - Letter from the editor.

PMID- 24927260
TI  - Perceived stress latent factors and the burnout subtypes: a structural model in
      dental students.
AB  - BACKGROUND: Students of health-professions suffer high levels of stress and
      burnout. The aim of the present study was to evaluate the relationship between
      perceived stress latent factors ('tenseness' and 'frustration') and the features
      ('overload', 'lack of development' and 'neglect') of the three burnout subtypes
      ('frenetic', 'under-challenged' and 'worn-out', respectively), in a sample of
      Spanish dental students. METHODS: The study employed a cross-sectional design. A
      sample of Spanish dental students (n = 314) completed the 'Perceived Stress
      Questionnaire' and the 'Burnout Clinical Subtype Questionnaire Student Survey'.
      The associations among variables were observed by means of structural equation
      modelling using the unweighted least squares method from polychoric correlations.
      RESULTS: Strong associations among perceived stress factors and the burnout
      characteristics were observed, although a distinct pattern of relations was
      observed for each burnout subtype. The 'overload' was moderately and positively
      associated with both 'tenseness' (0.45), and 'frustration' (0.38) dimensions of
      perceived stress; the 'lack of development' was positively associated with the
      'frustration' dimension (0.72), but negatively associated with 'tenseness' (
      0.69); the 'neglect' showed a weaker positive associated with 'frustration'
      (0.41), and a small negative association with 'tenseness' (-0.20). The model was
      a very good fit to the data (GFI  =  0.96; RSMR  =  0.07; AGFI = 0.96; NFI =
      0.95; RFI = 0.95). CONCLUSIONS: The stress factors of 'frustration' and
      'tenseness' seems to be related in a distinct way to the burnout subtypes in
      Spanish dental students. This finding suggests that intervention programs
      specifically tailored to these subtypes may be a promising future direction.

PMID- 24927263
TI  - Targeted therapies for treatment of recurrent ovarian cancer.
AB  - Ovarian cancer remains the leading cause of death among women with gynecologic
      malignancies in the United States. Most women with epithelial ovarian cancer
      present with advanced disease. Despite good response rates to initial surgery and
      chemotherapy, the majority of patients experience relapse and ultimately die of
      their disease. A better understanding of the molecular differences underlying the
      histologic subtypes of epithelial ovarian cancer has led to recent advances in
      targeted therapeutic strategies. Here we review the most promising targeted
      therapeutics currently being used for the treatment of recurrent ovarian cancer. 

PMID- 24927254
TI  - Chemical basis of interactions between engineered nanoparticles and biological
      systems.

PMID- 24927264
TI  - Treatment selection in metastatic renal cell carcinoma: more confusion or a path
      forward?
AB  - Meaningful progress has been realized in the treatment of metastatic renal cell
      carcinoma with the recent approval of a number of new agents; more new agents are
      on the horizon. Despite the recent completion of many clinical trials that have
      changed or will change practice, many questions remain. In this manuscript, we
      highlight the most noteworthy developments in the first- and second-line
      treatment of metastatic renal cell carcinoma, as these are the areas of greatest
      change. We also emphasize ongoing trials and those areas that are most in need of
      study in order to move the field forward. Although more data are needed, exciting
      progress is being made. 

PMID- 24927265
TI  - The clinical management of chronic myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) is an aggressive malignancy characterized
      by peripheral monocytosis and ineffective hematopoiesis. It has been historically
      classified as a subtype of the myelodysplastic syndromes (MDSs) but was recently
      demonstrated to be a distinct entity with a distinct natural history.
      Nonetheless, clinical practice guidelines for CMML have been inferred from
      studies designed for MDSs. It is imperative that clinicians understand which
      elements of MDS clinical practice are translatable to CMML, including which
      evidence has been generated from CMML-specific studies and which has not. This
      allows for an evidence-based approach to the treatment of CMML and identifies
      knowledge gaps in need of further study in a disease-specific manner. This review
      discusses the diagnosis, prognosis, and treatment of CMML, with the task of
      divorcing aspects of MDS practice that have not been demonstrated to be
      applicable to CMML and merging those that have been shown to be clinically
      similar. 

PMID- 24927267
TI  - Iron chelation for iron overload secondary to transfusions of packed red blood
      cells.

PMID- 24927266
TI  - Update on proteasome inhibitors in multiple myeloma.

PMID- 24927268
TI  - Aspirin, the new targeted therapy in colorectal cancer.

PMID- 24927269
TI  - Genetic engineering of T cells in leukemia and lymphoma.

PMID- 24927270
TI  - The evolutionary psychology of human mating: a response to Buller's critique.
AB  - In this paper, I critique arguments made by philosopher David Buller against
      central evolutionary-psychological explanations of human mating. Specifically, I
      aim to rebut his criticisms of Evolutionary Psychology regarding (1) women's long
      term mating preferences for high-status men; (2) the evolutionary rationale
      behind men's provisioning of women; (3) men's mating preferences for young women;
      (4) women's adaptation for extra-pair sex; (5) the sex-differentiated
      evolutionary theory of human jealousy; and (6) the notion of mate value. In sum,
      I aim to demonstrate that Buller's arguments contra Evolutionary Psychologists
      are left wanting. 

PMID- 24927271
TI  - A new tool for monoclonal antibody analysis: application of IdeS proteolysis in
      IgG domain-specific characterization.
AB  - Monoclonal antibody (mAb) products are extraordinarily heterogeneous due to the
      presence of a variety of enzymatic and chemical modifications, such as
      deamidation, isomerization, oxidation, glycosylation, glycation, and terminal
      cyclization. The modifications in different domains of the antibody molecule can
      result in different biological consequences. Therefore, characterization and
      routine monitoring of domain-specific modifications are essential to ensure the
      quality of the therapeutic antibody products. For this purpose, a rapid and
      informative methodology was developed to examine the heterogeneity of individual
      domains in mAb products. A recently discovered endopeptidase, IdeS, cleaves heavy
      chains below the hinge region, producing F(ab') 2 and Fc fragments. Following
      reduction of disulfide bonds, three antibody domains (LC, Fd, and Fc/2) can be
      released for further characterization. Subsequent analyses by liquid
      chromatography/mass spectrometry, capillary isoelectric focusing, and glycan
      mapping enable domain-specific profiling of oxidation, charge heterogeneity, and
      glycoform distribution. When coupled with reversed phase chromatography, the
      unique chromatographic profile of each molecule offers a simple strategy for an
      identity test, which is an important formal test for biopharmaceutical quality
      control purposes. This methodology is demonstrated for a number of IgGs of
      different subclasses (IgG1, IgG2, IgG4), as well as an Fc fusion protein. The
      presented technique provides a convenient platform approach for scientific and
      formal therapeutic mAb product characterization. It can also be applied in
      regulated drug substance batch release and stability testing of antibody and Fc
      fusion protein products, in particular for identity and routine monitoring of
      domain-specific modifications. 

PMID- 24927272
TI  - O-glycosylation of glycine-serine linkers in recombinant Fc-fusion proteins:
      attachment of glycosaminoglycans and other intermediates with phosphorylation at
      the xylose sugar subunit.
AB  - A xylose-based glycosaminoglycan (GAG) core was recently identified at a Ser
      residue in the linker sequence of a recombinant Fc fusion protein. The linker
      sequence, G-S-G-G-G-G, and an upstream acidic residue were serving as a substrate
      for O-xylosyltransferase, resulting in a major glycan composed of Xyl-Gal-Gal
      GlcA and other minor intermediates. In this paper, a portion of an unrelated
      protein was fused to the C-terminus of an IgG Fc domain using the common (G4S) 4
      linker repeat. This linker resulted in a heterogenous population of xylose-based
      glycans all containing at least a core Xyl. Commonly observed glycan structures
      include GAG-related di-, tri-, tetra-, and penta-saccharides (e.g., Xyl-Gal, Xyl
      Gal-Gal, Xyl-Gal-Gal-GlcA, and Xyl-Gal-Gal-GlcA-HexNAc), as well as Xyl-Gal
      Neu5Ac. Following alkaline phosphatase or sialidase treatment combined with CID
      fragmentation, low-level glycans with a mass addition of 79.9 Da were confirmed
      to be a result of phosphorylated xylose. A minute quantity of phosphorylated GAG
      pentasaccharides may also be sulfated (also 79.9 Da), possibly at the HexNAc
      moiety due to non-reactivity to alkaline phosphatase. The xylose moiety may be
      randomly incorporated in one of the three G-S-G sequence motifs; and the linker
      peptide shows evidence for multiple additions of xylose at very low levels. 

PMID- 24927273
TI  - Highly parallel characterization of IgG Fc binding interactions.
AB  - Because the variable ability of the antibody constant (Fc) domain to recruit
      innate immune effector cells and complement is a major factor in antibody
      activity in vivo, convenient means of assessing these binding interactions is of
      high relevance to the development of enhanced antibody therapeutics, and to
      understanding the protective or pathogenic antibody response to infection,
      vaccination, and self. Here, we describe a highly parallel microsphere assay to
      rapidly assess the ability of antibodies to bind to a suite of antibody
      receptors. Fc and glycan binding proteins such as FcgammaR and lectins were
      conjugated to coded microspheres and the ability of antibodies to interact with
      these receptors was quantified. We demonstrate qualitative and quantitative
      assessment of binding preferences and affinities across IgG subclasses, Fc domain
      point mutants, and antibodies with variant glycosylation. This method can serve
      as a rapid proxy for biophysical methods that require substantial sample
      quantities, high-end instrumentation, and serial analysis across multiple binding
      interactions, thereby offering a useful means to characterize monoclonal
      antibodies, clinical antibody samples, and antibody mimics, or alternatively, to
      investigate the binding preferences of candidate Fc receptors. 

PMID- 24927275
TI  - Modulatory effect of acupuncture at Waiguan (TE5) on the functional connectivity
      of the central nervous system of patients with ischemic stroke in the left basal
      ganglia.
AB  - OBJECTIVE: To study the influence of acupuncture at Waiguan (TE5) on the
      functional connectivity of the central nervous system of patients with ischemic
      stroke. METHODS: Twenty-four patients with ischemic stroke in the left basal
      ganglia were randomized based on gender to receive TE5 acupuncture (n = 12) or
      nonacupoint acupuncture (n = 12). Each group underwent sham acupuncture and then
      verum acupuncture while being scanned with functional magnetic resonance imaging.
      Six regions of interest (ROI) were defined, including bilateral motor,
      somatosensory, and bilateral basal ganglia areas. The functional connectivity
      between these ROIs and all voxels of the brain was analyzed in Analysis of
      Functional NeuroImages (AFNI) to explore the differences between verum
      acupuncture and sham acupuncture at TE5 and between TE5 acupuncture and
      nonacupoint acupuncture. The participants were blinded to the allocation. RESULT:
      The effect of acupuncture on six seed-associated networks was explored. The
      result demonstrated that acupuncture at Waiguan (TE5) can regulate the
      sensorimotor network of the ipsilesional hemisphere, stimulate the contralesional
      sensorimotor network, increase cooperation of bilateral sensorimotor networks,
      and change the synchronization between the cerebellum and cerebrum. Furthermore,
      a lot of differences of effect existed between verum acupuncture and sham
      acupuncture at TE5, but there was little difference between TE5 acupuncture and
      nonacupoint acupuncture. CONCLUSION: The modulation of synchronizations between
      different regions within different brain networks might be the mechanism of
      acupuncture at Waiguan (TE5). Stimulation of the contralesional sensorimotor
      network and increase of cooperation of bilateral hemispheres imply a compensatory
      effect of the intact hemisphere, whereas changes in synchronization might
      influence the sensorimotor function of the affected side of the body. TRIAL
      REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ONRC-08000255.

PMID- 24927277
TI  - g-Jitter mixed convective slip flow of nanofluid past a permeable stretching
      sheet embedded in a Darcian porous media with variable viscosity.
AB  - The unsteady two-dimensional laminar g-Jitter mixed convective boundary layer
      flow of Cu-water and Al2O3-water nanofluids past a permeable stretching sheet in
      a Darcian porous is studied by using an implicit finite difference numerical
      method with quasi-linearization technique. It is assumed that the plate is
      subjected to velocity and thermal slip boundary conditions. We have considered
      temperature dependent viscosity. The governing boundary layer equations are
      converted into non-similar equations using suitable transformations, before being
      solved numerically. The transport equations have been shown to be controlled by a
      number of parameters including viscosity parameter, Darcy number, nanoparticle
      volume fraction, Prandtl number, velocity slip, thermal slip, suction/injection
      and mixed convection parameters. The dimensionless velocity and temperature
      profiles as well as friction factor and heat transfer rates are presented
      graphically and discussed. It is found that the velocity reduces with velocity
      slip parameter for both nanofluids for fluid with both constant and variable
      properties. It is further found that the skin friction decreases with both Darcy
      number and momentum slip parameter while it increases with viscosity variation
      parameter. The surface temperature increases as the dimensionless time increases
      for both nanofluids. Nusselt numbers increase with mixed convection parameter and
      Darcy numbers and decreases with the momentum slip. Excellent agreement is found
      between the numerical results of the present paper with published results. 

PMID- 24927276
TI  - Binocular neurons in parastriate cortex: interocular 'matching' of receptive
      field properties, eye dominance and strength of silent suppression.
AB  - Spike-responses of single binocular neurons were recorded from a distinct part of
      primary visual cortex, the parastriate cortex (cytoarchitectonic area 18) of
      anaesthetized and immobilized domestic cats. Functional identification of neurons
      was based on the ratios of phase-variant (F1) component to the mean firing rate
      (F0) of their spike-responses to optimized (orientation, direction, spatial and
      temporal frequencies and size) sine-wave-luminance-modulated drifting grating
      patches presented separately via each eye. In over 95% of neurons, the
      interocular differences in the phase-sensitivities (differences in F1/F0 spike
      response ratios) were small (<= 0.3) and in over 80% of neurons, the interocular
      differences in preferred orientations were <= 10 degrees . The interocular
      correlations of the direction selectivity indices and optimal spatial
      frequencies, like those of the phase sensitivies and optimal orientations, were
      also strong (coefficients of correlation r >= 0.7005). By contrast, the
      interocular correlations of the optimal temporal frequencies, the diameters of
      summation areas of the excitatory responses and suppression indices were weak
      (coefficients of correlation r <= 0.4585). In cells with high eye dominance
      indices (HEDI cells), the mean magnitudes of suppressions evoked by stimulation
      of silent, extra-classical receptive fields via the non-dominant eyes, were
      significantly greater than those when the stimuli were presented via the dominant
      eyes. We argue that the well documented 'eye-origin specific' segregation of the
      lateral geniculate inputs underpinning distinct eye dominance columns in primary
      visual cortices of mammals with frontally positioned eyes (distinct eye dominance
      columns), combined with significant interocular differences in the strength of
      silent suppressive fields, putatively contribute to binocular stereoscopic
      vision.

PMID- 24927278
TI  - Determination of irinotecan and its metabolite SN-38 in rabbit plasma and tumors
      using a validated method of tandem mass spectrometry coupled with liquid
      chromatography.
AB  - New tandem mass spectrometric method coupled with liquid chromatography (LC
      MS/MS) has been developed to determine the total concentration of camptothecin
      derivatives (irinotecan and SN-38) regardless of inter-conversion phenomenon
      between carboxylate and lactone forms. At first, all sample solutions were
      acidified for 1h in order to completely convert CPT derivatives into their
      lactone forms and then CPT derivatives were extracted with organic solution
      containing diethyl ether and ethyl acetate (2:1, v/v) just after alkalization in
      the range pH 8.0-8.5 in acid-treated solutions. Analytes were separated on a
      reverse phase C18 column (150*2.1mm) and eluted isocratically with a mobile phase
      which consisted of acetonitrile-methanol-buffer (0.1% formic acid, 5mM ammonium
      formate) (3:4:3, v/v). CPT derivatives were monitored by tandem mass spectrometry
      in electrospay-positive ionization and multiple reaction mode programmed to the
      following transitions (m/z): '587.6->167.2' of CPT-11, '393.6->349.3' of SN-38
      and '349.4-> 305.2' of CPT. The method was validated to have the proper linearity
      (r(2)>0.99) over the range of 5-1000ng/ml of CPT-11 and 1-250ng/ml of SN-38 with
      good accuracy (89.8-114.3%) and precision (less than 10%). In all stability
      tests, concentration of CPT-11 and SN-38 had been left in the acceptable range of
      88.8-110.7% when sample solutions were acidified before determination of CPT
      derivatives. Newly developed LC-MS/MS method was suitable for the determination
      of CPT derivatives of both rabbit plasma and tumor tissues in the pharmacokinetic
      study. 

PMID- 24927279
TI  - Enactment versus observation: item-specific and relational processing in goal
      directed action sequences (and lists of single actions).
AB  - What are the memory-related consequences of learning actions (such as "apply the
      patch") by enactment during study, as compared to action observation? Theories
      converge in postulating that enactment encoding increases item-specific
      processing, but not the processing of relational information. Typically, in the
      laboratory enactment encoding is studied for lists of unrelated single actions in
      which one action execution has no overarching purpose or relation with other
      actions. In contrast, real-life actions are usually carried out with the
      intention to achieve such a purpose. When actions are embedded in action
      sequences, relational information provides efficient retrieval cues. We
      contrasted memory for single actions with memory for action sequences in three
      experiments. We found more reliance on relational processing for action-sequences
      than single actions. To what degree can this relational information be used after
      enactment versus after the observation of an actor? We found indicators of
      superior relational processing after observation than enactment in ordered pair
      recall (Experiment 1A) and in emerging subjective organization of repeated recall
      protocols (recall runs 2-3, Experiment 2). An indicator of superior item-specific
      processing after enactment compared to observation was recognition (Experiment
      1B, Experiment 2). Similar net recall suggests that observation can be as good a
      learning strategy as enactment. We discuss possible reasons why these findings
      only partly converge with previous research and theorizing. 

PMID- 24927280
TI  - Multiparametric MRI analysis for the identification of high intensity focused
      ultrasound-treated tumor tissue.
AB  - PURPOSE: In this study endogenous magnetic resonance imaging (MRI) biomarkers for
      accurate segmentation of High Intensity Focused Ultrasound (HIFU)-treated tumor
      tissue and residual or recurring non-treated tumor tissue were identified.
      METHODS: Multiparametric MRI, consisting of quantitative T1, T2, Apparent
      Diffusion Coefficient (ADC) and Magnetization Transfer Ratio (MTR) mapping, was
      performed in tumor-bearing mice before (n = 14), 1 h after (n = 14) and 72 h (n =
      7) after HIFU treatment. A non-treated control group was included (n = 7).
      Cluster analysis using the Iterative Self Organizing Data Analysis (ISODATA)
      technique was performed on subsets of MRI parameters (feature vectors). The
      clusters resulting from the ISODATA segmentation were divided into a viable and
      non-viable class based on the fraction of pixels assigned to the clusters at the
      different experimental time points. ISODATA-derived non-viable tumor fractions
      were quantitatively compared to histology-derived non-viable tumor volume
      fractions. RESULTS: The highest agreement between the ISODATA-derived and
      histology-derived non-viable tumor fractions was observed for feature vector {T1,
      T2, ADC}. R1 (1/T1), R2 (1/T2), ADC and MTR each were significantly increased in
      the ISODATA-defined non-viable tumor tissue at 1 h after HIFU treatment compared
      to viable, non-treated tumor tissue. R1, ADC and MTR were also significantly
      increased at 72 h after HIFU. CONCLUSIONS: This study demonstrates that non
      viable, HIFU-treated tumor tissue can be distinguished from viable, non-treated
      tumor tissue using multiparametric MRI analysis. Clinical application of the
      presented methodology may allow for automated, accurate and objective evaluation
      of HIFU treatment.

PMID- 24927281
TI  - Genetic architecture of winter hardiness and frost tolerance in triticale.
AB  - Abiotic stress experienced by autumn-sown crops during winter is of great
      economic importance as it can have a severe negative impact on yield. In this
      study, we investigated the genetic architecture of winter hardiness and frost
      tolerance in triticale. To this end, we used a large mapping population of 647 DH
      lines phenotyped for both traits in combination with genome-wide marker data.
      Employing multiple-line cross QTL mapping, we identified nine main effect QTL for
      winter hardiness and frost tolerance of which six were overlapping between both
      traits. Three major QTL were identified on chromosomes 5A, 1B and 5R. In
      addition, an epistasis scan revealed the contribution of epistasis to the genetic
      architecture of winter hardiness and frost tolerance in triticale. Taken
      together, our results show that winter hardiness and frost tolerance are complex
      traits that can be improved by phenotypic selection, but also that genomic
      approaches hold potential for a knowledge-based improvement of these important
      traits in elite triticale germplasm. 

PMID- 24927282
TI  - On the importance of relative salience: comparing overt selection behavior of
      single versus simultaneously presented stimuli.
AB  - The goal of the current study was to investigate time-dependent effects of the
      number of targets presented and its interaction with stimulus salience on
      oculomotor selection performance. To this end, observers were asked to make a
      speeded eye movement to a target orientation singleton embedded in a homogeneous
      background of vertically oriented lines. In Experiment 1, either one or two
      physically identical targets were presented, whereas in Experiment 2 an
      additional orientation-based salience manipulation was performed. The results
      showed that the probability of a singleton being available for selection is
      reduced in the presence of an identical singleton (Experiment 1) and that this
      effect is modulated by the salience of the other singleton (Experiment 2). While
      the absolute orientation contrast of a target relative to the background
      contributed to the probability that it is available for selection, the crucial
      factor affecting selection was the relative salience between singletons. These
      findings are incompatible with a processing speed account, which highlights the
      importance of visibility and claims that a certain singleton identity has a
      unique speed with which it can be processed. In contrast, the finding that the
      number of targets presented affected a target's availability suggests an
      important role of the broader display context in determining oculomotor selection
      performance. 

PMID- 24927283
TI  - Role of nicotine dependence in the association between the dopamine receptor gene
      DRD3 and major depressive disorder.
AB  - BACKGROUND: The aims of this study were to analyze associations of dopamine
      receptor genes (DRD1-5) with Major Depressive Disorder (MDD) and nicotine
      dependence (ND), and to investigate whether ND moderates genetic influences on
      MDD. METHODS: The sample was ascertained from the Finnish Twin Cohort. Twin pairs
      concordant for smoking history were recruited along with their family members, as
      part of the multisite Nicotine Addiction Genetics consortium. Genetic association
      analyses were based on 1428 adults. Total of 70 tagging single nucleotide
      polymorphisms within the dopamine receptor genes were genotyped and analyzed for
      association with MDD, ND, and MD-ND co-morbidity. Individual level logistic
      regression analyses were based on 1296 adults with data on ND and MDD diagnoses,
      as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use.
      Four independent samples, such as population-based and case-control samples, were
      used for replication. RESULTS: Rs2399496, located 1.5 kb downstream of DRD3,
      showed suggestive association for MDD (p = 0.00076) and significant association
      for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND
      interaction justified analyses by genetic risk variant and ND status. Individuals
      with ND and two minor alleles (AA) of rs2399496 had almost six-fold risk for MDD
      (OR 5.74, 95%CI 3.12-10.5, p = 9.010e-09) compared to individuals without ND and
      with two major alleles (TT). CONCLUSIONS: Significant association between a
      variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our
      results further suggest that nicotine dependence may potentiate the influence of
      the DRD3 genetic variant on MDD.

PMID- 24927286
TI  - 24(S)-Saringosterol from edible marine seaweed Sargassum fusiforme is a novel
      selective LXRbeta agonist.
AB  - Dietary phytosterols have been successfully used for lowering cholesterol levels,
      which correlates with the fact that some phytosterols are able to act as liver X
      receptor (LXR) agonists. Sargassum fusiforme is an edible marine seaweed well
      known for its antiatherosclerotic function in traditional Chinese medicine. In
      this study, seven phytosterols including fucosterol (1), saringosterol (2), 24
      hydroperoxy-24-vinyl-cholesterol (3), 29-hydroperoxy-stigmasta-5,24(28)-dien
      3beta-ol (4), 24-methylene-cholesterol (5), 24-keto-cholesterol (6), and
      5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (7) were purified and evaluated
      for their actions on LXR-mediated transcription using a reporter assay. Among
      these phytosterols, 2 was the most potent compound in stimulating the
      transcriptional activities of LXRalpha by (3.81+/-0.15)-fold and LXRbeta by
      (14.40+/-1.10)-fold, respectively. Two epimers of 2, 24(S)-saringosterol (2a) and
      24(R)-saringosterol (2b), were subsequently separated by semipreparative high
      performance liquid chromatography. Interestingly, 2a was more potent than 2b in
      LXRbeta-mediated transactivation ((3.50+/-0.17)-fold vs (1.63+/-0.12)-fold)
      compared with control. Consistently, 2a induced higher expression levels of LXR
      target genes including key players in reverse cholesterol transport in six cell
      lines. These data along with molecular modeling suggested that 2a acts as a
      selective LXRbeta agonist and is a potent natural cholesterol-lowering agent.
      This study also demonstrated that phytosterols in S. fusiforme contributed to the
      well-known antiatherosclerotic function.

PMID- 24927287
TI  - "Mobile" medicine: a surprise encounter with placenta percreta.

PMID- 24927288
TI  - The long and winding road.

PMID- 24927285
TI  - The multiple roles of hypothetical gene BPSS1356 in Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is an opportunistic pathogen and the causative agent of
      melioidosis. It is able to adapt to harsh environments and can live
      intracellularly in its infected hosts. In this study, identification of
      transcriptional factors that associate with the beta' subunit (RpoC) of RNA
      polymerase was performed. The N-terminal region of this subunit is known to
      trigger promoter melting when associated with a sigma factor. A pull-down assay
      using histidine-tagged B. pseudomallei RpoC N-terminal region as bait showed that
      a hypothetical protein BPSS1356 was one of the proteins bound. This hypothetical
      protein is conserved in all B. pseudomallei strains and present only in the
      Burkholderia genus. A BPSS1356 deletion mutant was generated to investigate its
      biological function. The mutant strain exhibited reduced biofilm formation and a
      lower cell density during the stationary phase of growth in LB medium. Electron
      microscopic analysis revealed that the DeltaBPSS1356 mutant cells had a shrunken
      cytoplasm indicative of cell plasmolysis and a rougher surface when compared to
      the wild type. An RNA microarray result showed that a total of 63 genes were
      transcriptionally affected by the BPSS1356 deletion with fold change values of
      higher than 4. The expression of a group of genes encoding membrane located
      transporters was concurrently down-regulated in DeltaBPSS1356 mutant. Amongst the
      affected genes, the putative ion transportation genes were the most severely
      suppressed. Deprivation of BPSS1356 also down-regulated the transcriptions of
      genes for the arginine deiminase system, glycerol metabolism, type III secretion
      system cluster 2, cytochrome bd oxidase and arsenic resistance. It is therefore
      obvious that BPSS1356 plays a multiple regulatory roles on many genes. 

PMID- 24927289
TI  - The effect on perioperative bleeding of placental extraction from an exteriorized
      uterus during caesarean section.
AB  - OBJECTIVE: To evaluate the effect on perioperative bleeding of an alternative
      technique for Caesarean section, in which placental extraction is performed while
      the uterus is exteriorized. METHODS: We performed a retrospective matched cohort
      study using data obtained through chart review. Group 1 included women who had CS
      performed using the technique of placental removal while the uterus was
      exteriorized, and group 2 included women who had CS performed using the
      conventional method of placental removal from a non-exteriorized uterus. Women in
      each group were matched for number of previous Caesarean sections, indications
      for CS, and gestational age. The primary outcome was the difference between
      preoperative and postoperative hemoglobin concentrations. Secondary outcomes
      included the incidence of blood transfusion, estimated blood loss (EBL),
      operative time, the incidence of postoperative endometritis, and length of
      hospital stay. RESULTS: A total of 90 charts were reviewed (45 per group).
      Baseline clinical characteristics were similar in both groups. The mean decrease
      in hemoglobin concentration was 22% less in women who had placental extraction
      from an exteriorized uterus than in those who had the conventional placental
      extraction (13.2g/L vs. 16.9 g/L, P=0.016). Among secondary outcomes, women in
      group 1 had a lower mean EBL (531.1 mL vs. 691.1 mL, P<0.05) and a shorter mean
      duration of surgery (28.0 minutes vs. 40.5 minutes, P<0.05). CONCLUSION:
      Exteriorizing the uterus prior to removal of the placenta during CS may decrease
      intraoperative and immediate postoperative bleeding compared with the
      conventional technique. Further studies on this technique are indicated.

PMID- 24927290
TI  - Predicting the spontaneous onset of labour in post-date pregnancies: a population
      based retrospective cohort study.
AB  - OBJECTIVE: To estimate the probability of spontaneous onset of labour (SOL) among
      women with uncomplicated pregnancies who have reached 41+0 weeks and to examine
      the influence of maternal characteristics on this event. METHODS: We conducted a
      population-based retrospective cohort study of women with uncomplicated singleton
      pregnancies in cephalic presentation between 41+0 and 42+0 weeks' gestation.
      Detailed clinical information was obtained from the British Columbia Perinatal
      Data Registry. We determined the time from 41+0 weeks to the exact day and time
      of SOL, pre-labour Caesarean section, or onset of labour following induction. A
      Kaplan-Meier curve was created to estimate the probability of SOL. A Cox
      regression model was used to assess the independent influence of maternal age,
      parity, BMI, and pregnancy weight gain on the SOL, and to assess the extent to
      which prediction of SOL could be individualized according to a woman's
      characteristics. RESULTS: Among 15 253 women undelivered at 41+0 weeks, there was
      a 67.6% (95% CI 66.4% to 68.7%) chance of SOL by 41+6 weeks. Although SOL was
      statistically more likely in younger women, higher parity, lower BMI, and lower
      weight gain (P<0.01), the multivariable model's predictive ability was poor (c
      statistic 0.56). CONCLUSION: Maternal characteristics were not a strong
      determinant for successful individualized prediction of SOL in women with
      uncomplicated pregnancies reaching 41+0 weeks of gestation. Our population-based
      estimates of the daily occurrence of SOL can be used to inform discussions with
      women on when to offer induction of labour.

PMID- 24927291
TI  - Informed reproductive decision-making: the impact of providing fertility
      information on fertility knowledge and intentions to delay childbearing.
AB  - OBJECTIVE: To examine the impact of providing fertility information on personal
      levels of fertility knowledge and intentions to delay childbearing. METHODS:
      Participants (n=69 young childless women) were randomly assigned to either an
      experimental (fertility-related) or control (alcohol-related) informational
      intervention group. Subsequent to the exposure to information, participants
      completed a questionnaire measuring fertility knowledge and intentions for
      reproduction. We predicted that the provision of fertility-related information
      would result in greater fertility knowledge and less intention to delay
      childbearing among young childless women. RESULTS: The young women exposed to the
      brief fertility information intervention were significantly more likely to
      respond correctly to questions testing their fertility knowledge, and reported
      less intention to delay childbearing than the young women in the control group.
      CONCLUSION: This study provided evidence that providing fertility-related
      information contributes to greater reproductive knowledge and may affect
      childbearing intentions. Future research is warranted to examine the influence of
      fertility information on reproductive decision-making within a theoretical
      framework in order to ensure that subsequent information interventions maximize
      their effectiveness.

PMID- 24927284
TI  - The impact of the metabotropic glutamate receptor and other gene family
      interaction networks on autism.
AB  - Although multiple reports show that defective genetic networks underlie the
      aetiology of autism, few have translated into pharmacotherapeutic opportunities.
      Since drugs compete with endogenous small molecules for protein binding, many
      successful drugs target large gene families with multiple drug binding sites.
      Here we search for defective gene family interaction networks (GFINs) in 6,742
      patients with the ASDs relative to 12,544 neurologically normal controls, to find
      potentially druggable genetic targets. We find significant enrichment of
      structural defects (P <= 2.40E-09, 1.8-fold enrichment) in the metabotropic
      glutamate receptor (GRM) GFIN, previously observed to impact attention deficit
      hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of
      genes, previously implicated in cancer, is significantly enriched (P <= 3.83E-23,
      2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P
      <= 4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium
      activated action potentials at the neuronal synapse. We find that multiple
      defective gene family interactions underlie autism, presenting new translational
      opportunities to explore for therapeutic interventions.

PMID- 24927292
TI  - Do multiple attempts at embryo transfer affect clinical pregnancy rates?
AB  - OBJECTIVE: During an in vitro fertilization treatment cycle, having embryos
      retained in the catheter after embryo transfer is a relatively uncommon and
      frustrating event. The reported incidence of retained embryos varies between 1%
      and 8%. It can be difficult to explain this unwanted event to patients. We wished
      to determine the incidence and the effect on pregnancy rates of having embryos
      retained in the transfer catheter, followed by immediate completion of transfer.
      METHODS: We performed a retrospective chart review of all IVF cycles with embryos
      retained in the transfer catheter, followed by repeat transfer, between October
      2009 and March 2012. We reviewed IVF cycles with or without ICSI, and included
      fresh and frozen embryo transfer cycles. All embryos were transferred on the
      third day after oocyte retrieval. Transabdominal ultrasound was used for guidance
      during the embryo transfer. RESULTS: A total of 49 IVF treatment cycles with
      retained embryos that required re-transfer were identified. This represented 7.5%
      (49/652) of all IVF cycles with embryo transfer during that period. The clinical
      pregnancy rate in the repeat transfer group was 30.6% (15/49). The clinical
      pregnancy rate in all cycles in the same time period was 34.8% (227/652). These
      rates were not significantly different (P=0.521). CONCLUSION: Having to re
      transfer embryos retained in the transfer catheter does not have any significant
      effect on clinical pregnancy rates during IVF treatment cycles.

PMID- 24927293
TI  - Customized charts and their role in identifying pregnancies at risk because of
      fetal growth restriction.
AB  - Customized growth charts reduce complexity in antenatal care for the expectant
      mother and her clinicians by improving the distinction between physiological and
      pathological variation in fetal size. Their application in large databases has
      improved our understanding of the importance of intrauterine growth restriction
      and its antenatal recognition. Their implementation into clinical practice,
      together with the appropriate training and referral protocols, has been shown to
      reduce the risk of stillbirth. 

PMID- 24927294
TI  - Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy:
      executive summary.
AB  - OBJECTIVE: This executive summary presents in brief the current evidence assessed
      in the clinical practice guideline prepared by the Canadian Hypertensive
      Disorders of Pregnancy Working Group and published by Pregnancy Hypertension
      (http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext) to
      provide a reasonable approach to the diagnosis, evaluation, and treatment of the
      hypertensive disorders of pregnancy. EVIDENCE: Published literature was retrieved
      through searches of Medline, CINAHL, and The Cochrane Library in March 2012 using
      appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia,
      pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification,
      prediction, prevention, prognosis, treatment, postpartum follow-up). Results were
      restricted to systematic reviews, randomized control trials, controlled clinical
      trials, and observational studies published in French or English between January
      2006 and February 2012. Searches were updated on a regular basis and incorporated
      in the guideline to September 2013. Grey (unpublished) literature was identified
      through searching the websites of health technology assessment and health
      technology-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      VALUES: The quality of evidence in the guideline summarized here was rated using
      the criteria described in the Report of the Canadian Task Force on Preventative
      Health Care (Table 1).

PMID- 24927295
TI  - Paternal and maternal concerns for their very low-birth-weight infants
      transitioning from the NICU to home.
AB  - This study examines qualitatively the concerns and coping mechanisms of fathers
      and mothers of very low-birth-weight (VLBW; <1500 g) neonatal intensive care unit
      (NICU) infants as they transition to home from the NICU. In-depth, semistructured
      phone interviews were conducted with a sample of fathers and mothers of VLBW NICU
      infants in the Chicago area who had transitioned home, and parental concerns were
      examined during the transition to home. Phone interviews lasting 30 to 60 minutes
      were transcribed verbatim, and all interviews were coded using content and
      narrative analysis. Twenty-five parents (10 fathers, 15 mothers) of 16 VLBW
      infants who had an average gestational age of 29.5 weeks and an average NICU stay
      of 58.38 days completed the interview. Overriding concerns included pervasive
      uncertainty, lingering medical concerns, and partner-related adjustment concerns
      that differed by gender. A variety of resilient coping methods during this
      stressful transition are also described. Fathers and mothers of VLBW NICU
      graduates have evolving but often differing concerns as they transition from the
      NICU to home. Many of these concerns can be addressed with improved discharge
      information exchanges and anticipatory guidance. Supporting parents during this
      stressful and often difficult transition may lead to decreased family stress,
      improved care, and better infant outcomes.

PMID- 24927297
TI  - One-step synthesis of unsymmetrical N-alkyl-N'-aryl perylene diimides.
AB  - An efficient and facile protocol for the synthesis of unsymmetrical N-alkyl-N'
      aryl perylene diimides is reported that circumvents the need for multiple
      reaction steps. A number of unsymmetrical perylene diimides containing a
      solubilizing swallowtail alkyl group and a variety of substituted aryl groups can
      be prepared in a single step from a simple mixture of amines. 

PMID- 24927296
TI  - Differential promoter methylation of kinesin family member 1a in plasma is
      associated with breast cancer and DNA repair capacity.
AB  - Methylation alterations of CpG islands, CpG island shores and first exons are key
      events in the formation and progression of human cancer, and an increasing number
      of differentially methylated regions and genes have been identified in breast
      cancer. Recent studies of the breast cancer methylome using deep sequencing and
      microarray platforms are providing a novel insight on the different roles
      aberrant methylation plays in molecular subtypes of breast cancer. Accumulating
      evidence from a subset of studies suggests that promoter methylation of tumor
      suppressor genes associated with breast cancer can be quantified in circulating
      DNA. However, there is a paucity of studies that examine the combined presence of
      genetic and epigenetic alterations associated with breast cancer using blood
      based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor
      for breast cancer that has been measured in lymphocytes. We isolated plasma DNA
      from 340 participants in a breast cancer case control project to study promoter
      methylation levels of five genes previously shown to be associated with breast
      cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL.
      Methylation of at least one gene was found in 49% of the cases compared to 20% of
      the controls. Three of the four genes had receiver characteristic operator curve
      values of >= 0.50: MAL (0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promoter
      methylation was associated with breast cancer and inversely associated with DRC.
      This is the first evidence of a significant association between genetic and
      epigenetic alterations in breast cancer using blood-based tests. The potential
      diagnostic utility of these biomarkers and their relevance for breast cancer risk
      prediction should be examined in larger cohorts.

PMID- 24927298
TI  - Versatile synthesis of thiol- and amine-bifunctionalized silica nanoparticles
      based on the ouzo effect.
AB  - In this article, we report a novel, nanoprecipitation-based method for preparing
      silica nanoparticles with thiol and amine cofunctionalization. (3
      Mercaptopropyl)trimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS)
      were used as the organosilane precursors, which were subjected to acid-catalyzed
      polycondensation in an organic phase containing a water-miscible solvent (e.g.,
      dimethyl sulfoxide). A pale colloidal solution could be immediately formed when
      the preincubated organic phase was directly injected into water. The initial
      composition ratio between MPTMS and APTMS is an important factor governing the
      formation of nanoparticles. Specifically, large, unstable micrometer-sized
      particles were formed for preparation using MPTMS as the sole silane source. In
      contrast, when APTMS was used alone, no particles could be formed. By reducing
      the fraction of APTMS (or increasing that of MPTMS) in the initial mixture of
      organosilanes, the formation of nanometer-sized particles occurred at a critical
      fraction of APTMS (i.e., 25%). Remarkably, a tiny fraction (e.g., 1%) of APTMS
      was sufficient to produce stable nanoparticles with a hydrodynamic diameter of
      about 200 nm. Other factors that would also affect particle formation were
      determined. Moreover, an interesting temperature effect on particle formation was
      observed. The TEM micrographs show spherical nanospheres with mean sizes of 130
      150 nm in diameter. The solid-state (29)Si NMR spectra demonstrate that the
      hybrid silica materials contain fully and partially condensed silicon structures.
      The bifunctionalized silica nanoparticles have positive zeta potentials whose
      magnitudes are positively correlated with the amount of APTMS. The total thiol
      content, however, is negatively correlated with the amount of APTMS. The cationic
      nanoparticles can bind an antisense oligonucleotide in a composition-dependent
      manner. 

PMID- 24927300
TI  - Enantiomeric guests with the same signs of chiral optical responses.
AB  - The circular dichroism of non-racemic molecules, being guests of co-crystalline
      phases of s-PS films, has been studied. Unexpectedly, the chiral response of non
      racemic guest molecules does not depend on their R or S molecular chirality but
      essentially only on the polymer host supramolecular chirality. 

PMID- 24927301
TI  - Principles of practice from the European expert panel on the contemporary
      treatment of schizophrenia.
AB  - Providing optimal treatment for people with schizophrenia is a difficult long
      term problem for clinicians and healthcare providers. Over the years a variety of
      approaches to treatment have evolved and, until now, there have been no widely
      accepted standards for care. To determine the principles underpinning the best
      practice for schizophrenia treatment, an Expert Panel of European psychiatrists
      and psychologists has worked to distil current theory, collective practical
      experiences and published literature into 17 basic Principles of Practice . These
      are not intended to duplicate or replace local treatment policies or guidelines.
      Instead, they describe best practice in diagnosis, patient assessment and long
      term treatment of schizophrenia as it exists at the beginning of the 21st century
      and is likely to exist in the near future. The Principles of Practice broadly
      fall into four main categories: (1) assessment, diagnosis and care provision; (2)
      treatment in day-to-day practice; (3) building a positive therapeutic alliance;
      and (4) a long-term clinical commitment. Running through all the Principles are
      several common threads - the fundamental importance of the therapeutic alliance
      between the clinician and the patient, the need to plan both for treatment
      efficacy and avoidance of side-effects and the importance of long-term treatment
      planning. It is intended that psychiatrists and other healthcare professionals
      can use the Principles as a benchmark for optimum patient management, and as a
      tool when negotiating the future of local and national schizophrenia management
      services. Furthermore, the Principles of Practice represent a first step in the
      development of a new patient-centred philosophy for the care of people with
      schizophrenia. 

PMID- 24927302
TI  - Editorial.

PMID- 24927299
TI  - Effectiveness of a web- and mobile phone-based intervention to promote physical
      activity and healthy eating in middle-aged males: randomized controlled trial of
      the ManUp study.
AB  - BACKGROUND: The high number of adult males engaging in low levels of physical
      activity and poor dietary practices, and the health risks posed by these
      behaviors, necessitate broad-reaching intervention strategies. Information
      technology (IT)-based (Web and mobile phone) interventions can be accessed by
      large numbers of people, yet there are few reported IT-based interventions
      targeting males' physical activity and dietary practices. OBJECTIVE: This study
      examines the effectiveness of a 9-month IT-based intervention (ManUp) to improve
      the physical activity, dietary behaviors, and health literacy in middle-aged
      males compared to a print-based intervention. METHODS: Participants, recruited
      offline (eg, newspaper ads), were randomized into either an IT-based or print
      based intervention arm on a 2:1 basis in favor of the fully automated IT-based
      arm. Participants were adult males aged 35-54 years living in 2 regional cities
      in Queensland, Australia, who could access the Internet, owned a mobile phone,
      and were able to increase their activity level. The intervention, ManUp, was
      based on social cognitive and self-regulation theories and specifically designed
      to target males. Educational materials were provided and self-monitoring of
      physical activity and nutrition behaviors was promoted. Intervention content was
      the same in both intervention arms; only the delivery mode differed. Content
      could be accessed throughout the 9-month study period. Participants' physical
      activity, dietary behaviors, and health literacy were measured using online
      surveys at baseline, 3 months, and 9 months. RESULTS: A total of 301 participants
      completed baseline assessments, 205 in the IT-based arm and 96 in the print-based
      arm. A total of 124 participants completed all 3 assessments. There were no
      significant between-group differences in physical activity and dietary behaviors
      (P>=.05). Participants reported an increased number of minutes and sessions of
      physical activity at 3 months (exp(beta)=1.45, 95% CI 1.09-1.95; exp(beta)=1.61,
      95% CI 1.17-2.22) and 9 months (exp(beta)=1.55, 95% CI 1.14-2.10; exp(beta)=1.51,
      95% CI 1.15-2.00). Overall dietary behaviors improved at 3 months
      (exp(beta)=1.07, 95% CI 1.03-1.11) and 9 months (exp(beta)=1.10, 95% CI 1.05
      1.13). The proportion of participants in both groups eating higher-fiber bread
      and low-fat milk increased at 3 months (exp(beta)=2.25, 95% CI 1.29-3.92;
      exp(beta)=1.65, 95% CI 1.07-2.55). Participants in the IT-based arm were less
      likely to report that 30 minutes of physical activity per day improves health
      (exp(beta)=0.48, 95% CI 0.26-0.90) and more likely to report that vigorous
      intensity physical activity 3 times per week is essential (exp(beta)=1.70, 95% CI
      1.02-2.82). The average number of log-ins to the IT platform at 3 and 9 months
      was 6.99 (SE 0.86) and 9.22 (SE 1.47), respectively. The average number of self
      monitoring entries at 3 and 9 months was 16.69 (SE 2.38) and 22.51 (SE 3.79),
      respectively. CONCLUSIONS: The ManUp intervention was effective in improving
      physical activity and dietary behaviors in middle-aged males with no significant
      differences between IT- and print-based delivery modes. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry: ACTRN12611000081910;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261100008191
      (Archived by WebCite at http://www.webcitation.org/6QHIWad63).

PMID- 24927303
TI  - Post-traumatic stress disorder: Hypotheses from clinical neuropsychology and
      psychopharmacology research.
AB  - Characteristic features of post-traumatic stress disorder (PTSD) include
      intrusive memories, avoidance, memory and concentration difficulties, and
      hyperalertness. Neuropsychological investigations of individuals with PTSD have
      suggested global and specific impairments of performance on standardized tests of
      memory. The use of the Emotional Stroop test has shown that trauma-related words
      are a sensitive measure of clinical state in PTSD patients. The Stroop paradigm
      has also shown that patients with PTSD appear to be characterized by implicit,
      explicit and autobiographical memory impairment. Available treatments for chronic
      post-traumatic stress disorder include cognitive-behaviour therapy, psychodynamic
      therapy and pharmacotherapy. Whereas drug treatment alone can rarely alleviate
      the suffering in PTSD, it appears to be most useful as an adjunct to
      psychotherapy. Tricyclic antidepressants are generally thought to be effective in
      alleviating symptoms, including nightmares, depression, sleep disorders and
      startle reactions, but are less able to relieve numbing. On the other hand,
      selective re-uptake blockers may be effective in decreasing numbing. However,
      rigorous clinical trials with double-blind placebo-controlled designs need to be
      performed to confirm these results. With new scientific discoveries in the
      understanding of PTSD, a new generation of pharmacological treatment is likely to
      emerge. (Int J Psych Clin Pract 2000; 4:3-18). 

PMID- 24927304
TI  - The challenges of diagnosis and continuing patient assessment.
AB  - The adoption of operational diagnostic principles, embodied in the current ICD
      and DSM methodologies, which are firmly based on the objective assessment of
      symptoms, has improved the reliability of schizophrenic diagnosis to levels
      roughly comparable with those of many other medical conditions of unknown
      aetiology. However, the differences between schizophrenia and the major affective
      disorders in terms of aetiology, pathology, course and outcome, and treatment
      response now appear less obvious than perhaps previously considered, bringing the
      validity of the current dichotomous classification of 'non-organic' psychoses
      into question. While this is an important area of current debate, it is
      imperative that present theorizing should not pull psychiatry back into the chaos
      of conflicting diagnostic ideologies which characterized thinking and practice
      for much of the 20th century. Despite some differences, the major diagnostic
      systems, ICD and DSM, have in their principles little to chose between them and
      can share credit in bringing about advantages that have been hard won. These
      systems should be used routinely in establishing a diagnosis of schizophrenia in
      everyday clinical practice. As stated in the Principles of Practice, establishing
      diagnosis is a key function of the clinician, but it is only one step in the
      complex process of patient evaluation, and one whose prominence may decline with
      increasing time and certainty. While the emphasis may vary over time, effective
      and comprehensive care should incorporate regular multidimensional, 'needs-based'
      and risk assessments covering a wide range of parameters, ensuring that the
      effects of variation in the individual patient over time can be understood and
      put into context in treatment planning. This may be best achieved in the context
      of a positive, stable and lasting relationship between the psychiatrist and
      patient. Establishing such a trusting and therapeutic relationship responsive to
      changing needs that will extend over years, represents both one of the greatest
      challenges and one of the most rewarding aspects of clinical medicine. 

PMID- 24927305
TI  - The efficacy of zotepine in schizophrenia: A meta-analysis of BPRS and
      improvement scale scores.
AB  - OBJECT: To assess the efficacy of the antipsychotic drug zotepine in the
      treatment of the global psychopathology of schizophrenia. METHOD: Fifteen
      randomized placebo- or antipsychotic comparator- controlled trials were analysed,
      using the Brief Psychiatric Rating Scale (BPRS) or other improvement scales. A
      meta-analysis of standardized treatment differences and a test for homogeneity
      were performed on four comparator groups: all placebo-controlled trials, all
      antipsychotic comparator-controlled trials, conventional antipsychotic comparator
      controlled trials, and antipsychotic comparator-controlled trials excluding those
      in which the dosage for zotepine exceeded 75-300 mg/day (the recommended dose in
      the UK). The outcome measure used in the meta-analysis was the change in rating
      score. RESULTS: Meta-analysis of the placebo-controlled trials showed that a
      significantly greater reduction in BPRS occurred with zotepine therapy than with
      placebo therapy. The reduction in rating score was also greater with zotepine
      therapy than with antipsychotic comparators. Exclusion of the high-dose zotepine
      studies did not alter these conclusions. Only in one trial, in which zotepine was
      compared with the atypical antipsychotic clozapine, was there a greater reduction
      in rating score with the comparator than with zotepine (not statistically
      significant). All tests of homogeneity failed to reach significance,
      demonstrating that the data were not influenced by inter-study heterogeneity.
      CONCLUSION: Zotepine is at least as effective against all psychopathological
      symptoms of schizophrenia as conventional antipsychotics. (Int J Psych Clin Pract
      2000; 4:19-27).

PMID- 24927306
TI  - From first episode to long-term care: The need for sustained clinical commitment.
AB  - There is considerable evidence to suggest that many patients experience
      difficulties in gaining access to treatment after the onset of significant
      symptoms and social disability. Delay in obtaining appropriate support and
      treatment can have profound effects on both the patient and their family and may
      also be associated with a poorer long-term outcome. As stated in the Principles
      of Practice, prompt and comprehensive clinical assessment, by a clinician
      experienced in the recognition and treatment of severe mental illness, is
      therefore important for achieving the best possible outcome for the patient. The
      primary objectives of early-stage treatment for schizophrenia are to achieve a
      full improvement in psychopathological symptoms and a recovery of premorbid
      levels of function. However, even with optimal treatment, the reality for many
      patients is that their symptoms and impairment continue. Many patients can
      therefore be regarded as only partially responsive, or even resistant, to
      treatment. When assessing the utility of an antipsychotic treatment regimen for
      such patients, clinicians should not just consider the objective manifestations
      of the disorder but also the subjective experience of the patient. Relapse of
      illness is also a common and serious problem for many patients with
      schizophrenia, despite continual treatment. Prevention and management of relapse
      are two of the main challenges in the effective treatment of schizophrenia. The
      optimal use of antipsychotic treatment and the adherence by patients to that
      treatment offer valuable protection against relapse. Symptoms of depression or
      low mood affect a high proportion of patients with schizophrenia at some point in
      their illness and are also associated with an increased risk of relapse.
      Treatment objectives in the early stages may need to be modified if a pattern of
      partial response or resistance to treatment, a cycle of relapse of the illness or
      the presence of depressive symptoms, develops. Clinicians should continue to
      offer a sustained and positive clinical commitment to all. 

PMID- 24927307
TI  - The importance of treatment acceptability to patients.
AB  - Antipsychotic drug treatment plays a central role in the care of patients with
      schizophrenia. The chronic nature of the illness means that most patients are
      likely to require long-term antipsychotic medication to alleviate symptoms and to
      prevent recurrence of an acute psychotic episode. Unfortunately, a high
      proportion of patients with schizophrenia do not comply with medication and this
      has profound consequences in terms of the number and severity of relapse
      episodes, rehospitalization rates, worsening of residual symptoms and social
      costs, including substance misuse, homelessness and the burden on carers.
      Ensuring that antipsychotic treatment is acceptable to the patient is fundamental
      to managing adherence. Side-effects, particularly mental and extrapyramidal
      symptoms (EPS), are the cause of much distress to patients and dissatisfaction
      with treatment, so a treatment regimen with a low side effect profile will help
      to improve adherence to the treatment. Such regimens have unmasked many of the
      other side-effects of treatment that were previously viewed as subsidiary to EPS;
      but the physical and psychological consequences of side-effects such as
      antipsychotic-induced sexual dysfunction or weight gain are highly distressing to
      the patient, and as likely as EPS to trigger non-adherence to medication.
      Consequently, careful selection of antipsychotic agent and dose regimens is
      essential to maximize the efficacy of the antipsychotic and to minimize the
      overall burden of side-effects. Satisfaction also depends very much on the extent
      to which the patient understands the treatment and its side-effects. Therefore, a
      close therapeutic alliance between the patient and the psychiatrist must underpin
      all attempts to increase the acceptability of treatment. This will allow the
      clinician to determine how the illness and its treatment are affecting all
      aspects of the life of the patient, and then to tailor the treatment continuously
      to obtain the best possible outcome for the patient. 

PMID- 24927308
TI  - Sexuality and quality of life of patients with schizophrenia.
AB  - Patients with schizophrenia continue to have sexual lives despite the nature of
      their illness. Sexuality, sexual relationships and sexual functioning are all
      important quality-of-life issues for these patients. Clinicians should be aware
      of this and not be hesitant to inquire as to the patient's experience and
      functioning in these areas. The importance of the patient's sexual life should be
      reflected in our quality of life questionnaires, and be incorporated as part of
      psychiatric rehabilitation programs through formal sex education. (Int J Psych
      Clin Pract 2000; 4:29-33). 

PMID- 24927309
TI  - Adult Attention Deficit Hyperactivity Disorder and comorbidity.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a chronic and incapacitating
      mental disorder characterized by overactivity, inattention and impulsiveness. The
      syndrome is usually diagnosed in childhood and it continues into adulthood.
      However, because the symptoms of ADHD frequently overlap with other categories of
      psychopathology, in adults it is often underdiagnosed or neglected, and left
      untreated. This paper emphasizes the importance of recognizing this syndrome in
      adulthood. To this end, we provide a review of the literature and four
      illustrative cases of our own. Appropriate treatment is also discussed. (Int J
      Psych Clin Pract 2000; 4:35-39). 

PMID- 24927310
TI  - The importance of psychosocial interventions and patient involvement in the
      treatment of schizophrenia.
AB  - The multifactorial nature of schizophrenia and the wide-ranging impact of the
      illness on the patient, their family, carers and healthcare providers mean that
      clinicians must be prepared to take a holistic approach to treatment. It is
      widely recognized that a patient's beliefs about their treatment and their
      experiences of schizophrenia can be very important in determining both attitude
      towards treatment compliance and behaviour in response to symptoms of the illness
      and environmental stress. Antipsychotic therapy remains the cornerstone of
      treatment for schizophrenia. However, there is now growing evidence to support
      the benefits of non-pharmacological interventions, when used in combination with
      antipsychotic treatment, in relieving symptoms, improving occupational and social
      functioning and reducing the risk of relapse. In particular, these interventions
      appear to provide benefits in coping skills and social and vocational
      functioning, as reflected in a greater ability to function independently and an
      improvement in quality of life. Systematic assessment of non-pharmacological
      therapies in schizophrenia is still a relatively new science, but there is good
      evidence that psychosocial therapies, such as family intervention therapy,
      cognitive-behaviour therapy and compliance therapy can markedly change a
      patient's behaviour and improve adherence to treatment and hence interaction with
      families, carers and healthcare providers. Psychosocial interventions can be
      implemented from the first episode of psychosis onwards and can contribute to an
      improved overall outcome in schizophrenia, to patients being more satisfied with
      their treatment, and to a better quality of life for the patient and their
      family. Initial comprehensive assessment will involve regular contact with the
      patient and opens channels for an ongoing dialogue. It is important that these
      discussions with the patients and their families and carers not only cover the
      need for social, emotional and behavioural support but include regular discussion
      of the acceptability and side-effects of antipsychotic treatment so that problems
      can be identified and addressed promptly. While the importance of non
      pharmacological interventions in improving the quality of patient care is
      becoming widely accepted, access to psychological, psycho-educational and family
      support is by no means universal in current clinical practice. It is important
      that these services, provided by appropriately trained personnel, are made
      available to all patients for whom they may be appropriate. 

PMID- 24927311
TI  - A prescription survey of the use of atypical antipsychotics for hospital
      inpatients in the United Kingdom.
AB  - OBJECT: Available efficacy data for atypical antipsychotics relate almost
      entirely to the use of atypicals alone. Previous surveys have, however, shown
      that typical antipsychotics are often co-prescribed alongside atypical drugs. We
      sought to evaluate prescribing of atypical antipsychotics to inpatients during
      one week of June 1998. METHOD: Requests for information were sent out to 229 UK
      centres which employed psychiatric pharmacists. From these, 143 (62%) responses
      were received, providing information on 3685 patients prescribed atypical
      antipsychotics. Data on patients prescribed an atypical for longer than 6 weeks
      were used as the primary indicator of prescribing practice. RESULTS: For all
      atypicals examined, co-prescription of typical drugs was commonplace. The
      proportions of patients receiving an atypical as the sole antipsychotic were:
      clozapine 56.5%, risperidone 27.6%, sertindole 27.1%, olanzapine 18.9%,
      quetiapine 9.7% and amisulpride 7.1%. Patients prescribed regular typical
      antipsychotics alongside atypical drugs were significantly more likely to be
      prescribed regular anticholinergic medication, indicating higher rates of acute
      extrapyramidal effects in those receiving antipsychotic polypharmacy. Atypical
      antipsychotics were prescribed alone in a minority of patients. CONCLUSIONS:
      Whilst there is some support for antipsychotic polypharmacy in certain cases,
      judging by strict evidence-based criteria the prescribing of atypical
      antipsychotics in our survey was poor. (Int J Psych Clin Pract 2000; 4:41-46).

PMID- 24927312
TI  - Sertindole is associated with a low level of extrapyramidal symptoms in
      schizophrenic patients: Results of a phase III trial.
AB  - OBJECT: The objective of this double-blind, multicentre study was to evaluate
      four doses of sertindole and haloperidol 10 mg. METHOD: The 617 schizophrenic
      patients were randomized to receive sertindole 8, 16, 20 or 24 mg/day or
      haloperidol 10 mg/day. Patients were assessed for extrapyramidal symptoms (EPS)
      using the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS), and for
      movement disorders using the Abnormal Involuntary Movement Scale (AIMS). RESULTS:
      Patients receiving haloperidol experienced significantly more EPS than patients
      receiving sertindole, supporting observations made in previous studies. The
      incidence of adverse events was similar for all doses of sertindole. SAS and BAS
      scores were significantly worse in the haloperidol group than in the sertindole
      groups. There were significantly greater increases in mean QT c interval in the
      sertindole groups than in the haloperidol group. Sertindole did not cause
      sedation. CONCLUSIONS: Sertindole is well tolerated and does not cause the
      debilitating EPS associated with traditional antipsychotic drugs. (Int J Psych
      Clin Pract 2000; 4:47-54).

PMID- 24927313
TI  - Opportunities and challenges presented by the new generation antipsychotics.
AB  - The widespread availability of the new generation of atypical antipsychotics
      offers the clinician valuable new opportunities to prescribe effective and well
      tolerated drug treatments for schizophrenia. As a group, the atypical
      antipsychotics are distinguished from the conventional agents by their lower
      propensity to induce extrapyramidal symptoms (EPS). In addition, some of these
      agents seem to be less likely to cause hyperprolactinaemia; this may contribute
      to a lower incidence of sexual and hormonal side-effects than with standard
      treatment regimens. EPS and sexual difficulties cause considerable distress to
      patients; there are grounds for predicting that better tolerability will lead to
      better compliance with treatment and thereby better long-term outcome. There is
      accumulating evidence that the atypical antipsychotics are more efficacious than
      the standard treatments; this may reflect greater tolerability and enhanced
      compliance with treatment, in addition to intrinsic efficacy. But, at the same
      time, the new treatments pose fresh challenges to the clinician. These agents
      differ from one another and the traditional antipsychotics in their pharmacology,
      side-effects and dosing requirements; clinicians are thus required to develop new
      treatment strategies, if these drugs are to be deployed to best effect. In
      particular, it is important that the new treatments are given rationally.
      Polypharmacy should be avoided, as this is unlikely to be more effective, and may
      lead to the tolerability benefits of the new agents being lost. Although
      clozapine is, rightly, reserved for treatment-resistant patients, on grounds of
      haematological safety, the practice of reserving other atypical antipsychotics
      for specific groups of patients, such as those with severe illness or established
      EPS, is misguided and results in the advantages of the atypical agents being
      denied to many patients who might otherwise have benefited greatly. These newer
      agents are best used within the setting of a strong therapeutic alliance between
      clinician and patient, in which an ongoing dialogue regarding symptoms, side
      effects and treatment expectations is an important element. Used rationally, they
      offer new opportunities for clinicians and renewed hope to many patients. 

PMID- 24927314
TI  - Sertindole improves both the positive and negative symptoms of schizophrenia:
      Results of a phase III trial.
AB  - OBJECTS: This large multicentre, double-blind, randomized study was designed to
      evaluate four doses of sertindole and haloperidol 10 mg in the treatment of
      patients with DSM-III-R schizophrenia. METHOD: 617 patients were randomized, of
      whom 595 were included in an intention-to-treat analysis. 375 patients completed
      the study. Patients were randomized to receive sertindole 8 mg/day, sertindole 16
      mg/day, sertindole 20 mg/day, sertindole 24 mg/day or haloperidol 10 mg/day for
      56days. Efficacy was assessed through the changes in score on the Positive and
      Negative Syndrome Scale (PANSS), and the Clinical Global Impressions (CGI) scale.
      Improvement in all end-points was observed for all treatment groups. RESULTS:
      Sertindole 16 mg showed significantly greater efficacy against negative symptoms
      than haloperidol 10 mg. The optimal dose of sertindole was 16 mg/day. Sertindole
      8 mg appeared to be suboptimal with respect to efficacy, and increasing the dose
      of sertindole above 20 mg did not appear to offer any additional benefit.
      Sertindole at all doses caused significantly fewer extrapyramidal symptoms than
      haloperidol. CONCLUSION: Sertindole is effective against positive and negative
      symptoms of schizophrenia within the dose range 12-24 mg daily, with an optimal
      starting dose of 16 mg daily. Efficacy is comparable to 10 mg of haloperidol with
      no difference in the time course of treatment response. The dose response
      relationship for efficacy with sertindole seems to plateau at about 16 mg daily
      with no demonstrable difference in increasing doses above this point. (Int J
      Psych Clin Pract 2000; 4:55-62).

PMID- 24927315
TI  - A time of opportunity in schizophrenia.
AB  - The European Expert Panel on the contemporary treatment of schizophrenia set out
      to create a document that would enhance the clinical practice of schizophrenia
      across Europe. Drawing on the interests and strengths of the multinational group,
      the Panel took a new look at the current management of schizophrenia and
      identified areas where common practice and best practice currently diverge.
      Thorough analysis of the literature plus critical clinical judgement has resulted
      in the Principles of Practice , which represent a new philosophy for the care of
      people with schizophrenia. This 17-point statement covers the entire range of
      schizophrenia management, from diagnosis and assessment of the first episode,
      through to long-term care of the patient with chronic illness. Much of the
      literature that informed the Panel discussion is presented in the papers that
      form this Supplement. 

PMID- 24927316
TI  - The relationship between objective sleep variables and subjective sleep
      estimation in schizophrenia.
AB  - AIM: Few investigations of sleep structure in schizophrenia have concentrated on
      the relationship between objective and subjective sleep variables. The aim of
      this study was to assess objective sleep variables and subjective estimation of
      sleep duration and sleep quality. METHODS: Polysomnography was performed in 20
      chronic patients with schizophrenia during three consecutive nights. After final
      awakenings subjects answered questions concerning subjective estimations of sleep
      duration, sleep latency, number of awakenings, and sleep depth. Pearson
      correlations between ranged subjective reports and objective sleep variables were
      performed. RESULTS: The results showed a high positive correlation between
      objective sleep latency and its subjective estimation; a positive correlation
      between subjective estimation of sleep depth and percentage of slow wave sleep
      (SWS%); a positive correlation between eye movement (EM) density and subjective
      estimation of wakefulness during the night; and a negative correlation between EM
      density and dream reports. CONCLUSION: We concluded that objective sleep
      variables are related to subjective sleep estimation in schizophrenic patients.
      In these patients, EM activity in REM sleep is related to the subjective feeling
      of wakefulness. (Int J Psych Clin Pract 2000; 4:63-67).

PMID- 24927317
TI  - Clomipramine-induced allergic hepatitis: A case report.
AB  - We describe a case history of a 41-year-old woman who developed an allergic
      hepatitis with massive eosinophilia and elevated hepatic transaminases secondary
      to clomipramine, a tricyclic antidepressant (TCA) drug. Although drug-induced
      allergic hepatitis during tricyclic antidepressant therapy is very rare, one
      should consider this diagnosis in the case of (right-sided) abdominal pain and
      fever whenever a TCA is used, especially during the second month of treatment.
      (Int J Psych Clin Pract 2000; 4:69-71). 

PMID- 24927318
TI  - Bullying and depression: A case report.
AB  - Bullying is common in schools and is often seen as an inevitable part of school
      life. Children who are bullied tend to be more anxious and insecure than their
      peers. We report the case of a 13-year-old boy who was bullied from the age of 9
      and presented to the local Child and Adolescent Mental Health Team (CAMHS) with a
      psychotic depression. Clinical improvement and re-integration into school was
      achieved by use of psychotropic medication and work on building self-esteem so
      that the patient could assert himself, both with peers and adults. There is
      evidence suggesting that children and adolescents who are bullied have increased
      rates of referral to the CAMHS, particularly with symptoms of depression. (Int J
      Psych Clin Pract 2000; 4:73-75). 

PMID- 24927320
TI  - Topics in contemporary psychiatric practice: Compliance in major psychoses.

PMID- 24927319
TI  - Long-term efficacy and safety of quetiapine in treatment-refractory
      schizophrenia: A case report.
AB  - The recent advent of atypical antipsychotics has provided new clinical options
      and set higher expectations for the treatment of schizophrenia. Such agents might
      more effectively prevent relapse because they are more effective against the full
      spectrum of schizophrenic symptoms, as well as having improved tolerability and
      leading to improved medication compliance. Quetiapine fumarate ('Seroquel') is a
      new dibenzothiazepine antipsychotic agent with a greater affinity for serotonin
      receptors than for dopamine receptors and with a lower propensity for producing
      extrapyramidal symptoms or increasing prolactin levels. It has recently been
      approved for the treatment of psychotic disorders; however, the long-term
      efficacy and safety of quetiapine for treating treatment-refractory schizophrenia
      is still being investigated. We present a case of a 58-year-old man suffering
      from chronic therapy-resistant schizophrenia, with both positive and negative
      symptoms, who was successfully treated with quetiapine for 5 years. To the best
      of our knowledge, this is the first report of such long beneficial use of
      quetiapine in a hospital clinical practice. (Int J Psych Clin Pract 2000; 4:77
      80). 

PMID- 24927323
TI  - Changes in histone H3 lysine 36 methylation in porcine oocytes and
      preimplantation embryos.
AB  - Histone H3 lysine 36 (H3K36) methylation is known to be associated with
      transcriptionally active genes, and is considered a genomic marker of active
      loci. To investigate the changes in H3K36 methylation in pig, we determined the
      mono-, di-, and tri-methylations of H3K36 (H3K36me1, H3K36me2 and H3K36me3,
      respectively) in porcine fetal fibroblasts, oocytes and preimplantation embryos
      by immunocytochemistry using specific antibodies and confocal microscopy. These
      analyses revealed that only H3K36me3 in porcine fetal fibroblasts consistently
      colocalized with transcription sites identified as actively synthesizing RNA
      based on fluorouridine (FU) incorporation. Treatment of cells with flavopiridol,
      which blocks transcription elongation, completely abrogated both H3K36me3 signals
      and RNA synthesis. All three types of H3K36 methylation were present and did not
      significantly differ during oocyte maturation. In parthenogenetic embryos,
      H3K36me1 and -me2 were detected in 1-cell through blastocyst-stage embryos. In
      contrast, H3K36me3 was not detected in most 1-cell stage embryos. H3K36me3
      signals became detectable in 2-cell stage embryos, peaked at the 4-cell stage,
      decreased at the 8-cell stage, and then became undetectable at blastocyst stages
      in both parthenogenetic and in vitro-fertilized (IVF) embryos. Unlike the case in
      IVF embryos, H3K36me3 could not be demethylated completely during the 1-cell
      stage in somatic cell nuclear transfer (SCNT) embryos. These results collectively
      indicate that H3K36me3, but not H3K36me1 or -me2, is associated with
      transcription elongation in porcine fetal fibroblasts. H3K36me3 is
      developmentally regulated and may be a histone mark of embryonic gene activation
      in pig. Aberrant H3K36 tri-methylation occurred during the nuclear reprogramming
      of SCNT embryos. 

PMID- 24927324
TI  - The 'stolen generations' of mothers and daughters: child apprehension and
      enhanced HIV vulnerabilities for sex workers of Aboriginal ancestry.
AB  - OBJECTIVES: The number of children in care of the state continues to grow in BC,
      Canada with a historical legacy of child apprehension among criminalized and
      marginalized populations, particularly women of Aboriginal ancestry and sex
      workers. However, there is a paucity of research investigating child apprehension
      experiences among marginalized mothers. The objective of the current analysis is
      to examine the prevalence and correlates of child apprehensions among female sex
      workers in Vancouver, Canada. METHODS: Analyses were drawn from the AESHA (An
      Evaluation of Sex Workers Health Access, 2010-present), a prospective cohort of
      street and off-street SWs, through outreach and semi-annual visits to the
      research office. Bivariate and multivariate logistic regression were used to
      examine correlates of child apprehension. RESULTS: Of a total of 510 SWs, 350
      women who had given birth to at least one child were included in the analyses
      (median age = 37 yrs: IQR: 31-44 yrs). The prevalence of child apprehension among
      mothers was 38.3%, with 37.4% reporting having been apprehended themselves by
      child welfare services. In multivariable analysis, servicing clients in outdoor
      public spaces (versus formal sex work establishments or informal indoor settings)
      (adjusted odds ratio, (aOR) = 2.73; 95%CI 1.27-5.90), history of injecting drugs
      (aOR  = 2.53; 95%CI 1.42-4.49), Aboriginal ancestry (aOR = 1.66; 95%CI 1.01-2.74)
      were associated with increased odds of child apprehension.
      DISCUSSION/CONCLUSIONS: Child apprehension rates are high, particularly among the
      most marginalized sex workers, including sex workers who use drugs and sex
      workers of Aboriginal ancestry. Structural reforms to child protection are
      urgently needed, that support family-based care address the historical legacy of
      colonization affecting Aboriginal peoples.

PMID- 24927325
TI  - Effect of MRE11 loss on PARP-inhibitor sensitivity in endometrial cancer in
      vitro.
AB  - AIM OF THE STUDY: To evaluate the frequency of MRE11/RAD50/NBS1 (MRN)-complex
      loss of protein expression in endometrial cancers (EC) and to determine whether
      loss of MRE11 renders the cancer cells sensitive to Poly(ADP-ribose) polymerase
      (PARP)-inhibitory treatment. METHODS: MRN expression was examined in 521 samples
      of endometrial carcinomas and in 10 cancer cell lines. A putative mutation
      hotspot in the form of an intronic poly(T) allele in MRE11 was sequenced in
      selected cases (n = 26). Sensitivity to the PARP-inhibitor, BMN673 was tested in
      colony formation assays before and after MRE11 silencing using siRNA. Homologous
      recombination (HR) DNA repair was evaluated by RAD51-foci formation assay upon
      irradiation and drug treatment. RESULTS: Loss of MRE11 protein was found in 30.7%
      of EC tumours and significantly associated with loss of RAD50, NBS1 and mismatch
      repair protein expression. One endometrial cell line showed a markedly reduced
      MRE11 expression due to a homozygous poly(T) mutation of MRE11, thereby
      exhibiting an increased sensitivity to BMN673. MRE11 depletion sensitizes MRE11
      expressing EC cell lines to the treatment with BMN673. The increased sensitivity
      to PARP-inhibition correlates with reduced RAD51 foci formation upon ionizing
      radiation in MRE11-depleted cells. CONCLUSION: Loss of the MRE11 protein predicts
      sensitivity to PARP-inhibitor sensitivity in vitro, defining it as an additional
      synthetic lethal gene with PARP. The high incidence of MRE11 loss in ECs can be
      potentially exploited for PARP-inhibitor therapy. Furthermore, MRE11 protein
      expression using immunohistochemistry could be investigated as a predictive
      biomarker for PARP-inhibitor treatment.

PMID- 24927326
TI  - Idiopathic pulmonary fibrosis: CT and risk of death.
AB  - PURPOSE: To investigate the prognostic value of quantitative computed tomographic
      (CT) scoring for the extent of fibrosis or emphysema in the context of a clinical
      model that includes the gender, age, and physiology ( GAP gender, age, and
      physiology model) of the patient. MATERIALS AND METHODS: Study cohorts were
      approved by local institutional review boards, and all patients provided written
      consent. This was a retrospective cohort study that included 348 patients (246
      men, 102 women; mean age, 69 years +/- 9) with idiopathic pulmonary fibrosis from
      two institutions. Fibrosis and emphysema visual scores were independently
      determined by two radiologists. Models were based on competing risks regression
      for death and were evaluated by using the C index and reclassification
      improvement. RESULTS: The CT- GAP gender, age, and physiology model (a
      modification of the original GAP gender, age, and physiology model that replaces
      diffusion capacity of carbon monoxide with CT fibrosis score) had accuracy
      comparable to that of the original GAP gender, age, and physiology model, with a
      C index of 70.3 (95% confidence interval: 66.4, 74.0); difference in C index
      compared with the GAP gender, age, and physiology model of -0.4 (95% confidence
      interval: -2.2, 3.4). The performance of the original GAP gender, age, and
      physiology model did not change significantly with the simple addition of
      fibrosis score, with a change in C index of 0.0 (95% confidence interval: -1.8,
      0.5) or of emphysema score, with a change in C index of 0.0 [95% confidence
      interval: -1.3, 0.4]). CONCLUSION: CT fibrosis score can replace diffusion
      capacity of carbon monoxide test results in a modified GAP gender, age, and
      physiology model (the CT- GAP gender, age, and physiology model) with comparable
      performance. This may be a useful alternative model in situations where CT
      scoring is more reliable and available than diffusion capacity of carbon
      monoxide.

PMID- 24927327
TI  - Treatment of metastatic posterior vertebral body osseous tumors by using a
      targeted bipolar radiofrequency ablation device: technical note.
AB  - PURPOSE: To evaluate the feasibility of use and safety of a targeted
      radiofrequency ablation (RFA) device for metastatic posterior vertebral body
      tumors. MATERIALS AND METHODS: This retrospective study was institutional review
      board approved and HIPAA compliant. Consent was waived for retrospective
      participation. Fluoroscopic or computed tomography-guided targeted RFA was
      performed in 26 patients (47 tumors) with painful metastatic posterior vertebral
      body tumors, some of which were radiation therapy resistant, by using a newly
      developed spinal tumor ablation system that contains an articulating bipolar
      extensible electrode. In 14 women and 12 men aged 44-85 years (mean age, 62
      years), the most common primary tumor was lung cancer in seven patients (27%) and
      renal cell carcinoma and sarcoma in five patients each (19%). Other tumors
      included breast cancer and melanoma in two patients each (8%) and colon cancer,
      multiple myeloma, neuroendocrine tumor, head and neck squamous cell carcinoma,
      and unknown primary tumor in one patient each (4%). Ablation was performed with
      device thermocouples that permitted real-time monitoring of the periphery of the
      ablation zones to determine ablation size. Sequential postprocedural pain scores
      were obtained. Thirteen patients underwent follow-up imaging, and one underwent
      subsequent biopsy of a treated area. A paired two-tailed Student t test was used
      to evaluate significance of postoperative visual analog scale scores of pain at 1
      week and 1 month. RESULTS: Four of 26 patients developed transient radicular
      symptoms after ablation, which resolved with transforaminal blocks. No permanent
      neurologic injuries resulted from the procedure. Intraprocedural imaging
      demonstrated that the articulating bipolar instrument could be navigated into the
      posterior vertebral body tumors with a transpedicular approach. Postablation
      imaging confirmed necrosis within the ablation zone. Three patients showed
      progression of disease at the treated levels at follow-up. Systemic therapy was
      not interrupted to perform the procedures. CONCLUSION: Targeted RFA with a newly
      developed articulating device is both feasible and safe for the treatment of
      painful posterior vertebral body metastatic tumors.

PMID- 24927328
TI  - Peptide-loaded nanoparticles and radionuclide imaging for individualized
      treatment of myocardial ischemia.
AB  - PURPOSE: To determine whether chitosan hydrogel nanoparticles loaded with
      vascular endothelial growth factor (VEGF) peptides (81-91 fragments) capable of
      targeting the ischemic myocardium enhance angiogenesis and promote therapeutic
      effects and whether radionuclide image-guided dosage control is feasible.
      MATERIALS AND METHODS: Experimental procedures and protocols were approved by the
      Institutional Animal Care and Use Committee. Rats (n = 32, eight per group) were
      subjected to myocardial ischemia (control group) and received chitosan hydrogel
      nanoparticles with VEGF165 proteins (chitosan VEGF) or VEGF81-91 peptides
      (chitosan peptides) via apical puncture. Ischemic hearts receiving chitosan
      without angiogenic factors served as the chitosan control. Myocardial perfusion
      was examined 7 days after surgery by using technetium 99m ((99m)Tc) tetrofosmin
      (37 MBq) autoradiography, and changes in vascular density with
      immunohistochemical staining were reviewed. Kruskal-Wallis test and Bonferroni
      corrected Mann-Whitney U test were used for multiple comparisons. Wilcoxon signed
      rank test was used to compare myocardial retention of (99m)Tc chitosan. RESULTS:
      Thirty minutes of myocardial ischemia resulted in perfusion defects (median, 54%;
      interquartile range [IQR], 41%-62%). Chitosan VEGF decreased perfusion defect
      extent (median, 68%; IQR, 63%-73%; P = .006 vs control) and increased vascular
      density (median, 81 vessels per high-power field; IQR, 72-100; P = .009 vs
      control). Administration of chitosan peptides reduced the degree of perfusion
      defects (median, 66%; IQR, 62%-73%; P = .006 vs control) and increased vascular
      density (median, 82 vessels; IQR, 78-92; P = .006 vs control). The effects of
      chitosan peptides on perfusion and vascular density were comparable to those seen
      with chitosan VEGF proteins (P = .713 and P = .833, respectively). Chitosan
      radiolabeled with (99m)Tc was administered twice at reperfusion with a 1-hour
      interval to determine whether image-guided dosage control is feasible. The hearts
      initially retained 4.6% (IQR, 4.1%-5.0%) of (99m)Tc chitosan administered and
      9.2% (IQR, 6.6%-12.7%; P = .068) with subsequent injection. CONCLUSION: VEGF
      peptides have angiogenic potential and resulted in therapeutic effectiveness.
      Adjunct use of single photon emission computed tomography was also demonstrated
      for individualized treatment of myocardial ischemia by further tailoring the
      therapeutic dosing. Online supplemental material is available for this article.

PMID- 24927330
TI  - Association of matrix metalloproteinase inducer (EMMPRIN) with the expression of
      matrix metalloproteinases-1, -2 and -9 during periapical lesion development.
AB  - OBJECTIVE: To evaluate the expression of matrix metalloproteinase inducer
      (EMMPRIN) and its correlation with the expression of matrix metalloproteinases
      (MMPs)-1, -2 and -9 during the development of periapical lesion in mice. METHODS:
      Periapical lesions were induced in the lower first molars of mice and after 7,
      14, 21 and 42 days the mandibles were removed. The periapical lesions were
      measured by micro-computed tomography. The expression of EMMPRIN, MMPs-1, -2, and
      -9 genes were determined by real-time RT-PCR. The location and expression of
      EMMPRIN and MMPs were evaluated by immunohistochemistry. RESULTS: At 14 days, the
      periapical lesion area was higher than at 7 days. At 21 and 42 days no
      statistically significant bone loss was observed in comparison to 14 days. The
      control group showed discrete and occasional EMMPRIM, MMP-1, -2 and -9
      immunostaining in the periodontal ligament fibroblasts. At 7, 14, 21 and 42 days
      intense immunoexpression was observed for EMMPRIN, MMPs-1, -2 and -9 in the
      region adjacent to the apical foramen. The EMMPRIN immunoexpression was higher at
      7, 14, 21 and 42 days compared with the control. There was a positive correlation
      between gene expression of EMMPRIN and MMPs in the active phase of periapical
      lesion development. CONCLUSION: There is a high expression of EMMPRIM mainly by
      the inflammatory infiltrate in the region adjacent to the apical foramen during
      periapical lesion development. Furthermore, the positive correlation with MMP-1, 
      2, and -9 during the first days after periapical lesion induction indicates that
      EMMPRIM may be involved in the active phase of periapical lesions development.

PMID- 24927329
TI  - Image-guided tumor ablation: standardization of terminology and reporting
      criteria--a 10-year update.
AB  - Image-guided tumor ablation has become a well-established hallmark of local
      cancer therapy. The breadth of options available in this growing field increases
      the need for standardization of terminology and reporting criteria to facilitate
      effective communication of ideas and appropriate comparison among treatments that
      use different technologies, such as chemical (eg, ethanol or acetic acid)
      ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused
      ultrasound, and cryoablation) and newer ablative modalities such as irreversible
      electroporation. This updated consensus document provides a framework that will
      facilitate the clearest communication among investigators regarding ablative
      technologies. An appropriate vehicle is proposed for reporting the various
      aspects of image-guided ablation therapy including classification of therapies,
      procedure terms, descriptors of imaging guidance, and terminology for imaging and
      pathologic findings. Methods are addressed for standardizing reporting of
      technique, follow-up, complications, and clinical results. As noted in the
      original document from 2003, adherence to the recommendations will improve the
      precision of communications in this field, leading to more accurate comparison of
      technologies and results, and ultimately to improved patient outcomes. Online
      supplemental material is available for this article .

PMID- 24927331
TI  - Hydrogen sulfide synergistically upregulates Porphyromonas gingivalis
      lipopolysaccharide-induced expression of IL-6 and IL-8 via NF-kappaB signalling
      in periodontal fibroblasts.
AB  - OBJECTIVES: The periodontal pathogen Porphyromonas gingivalis produces hydrogen
      sulfide (H2S). H2S in the oral cavity is positively correlated with periodontitis
      but the mechanism by which H2S contributes to periodontal diseases is obscure. We
      investigated the effect of H2S in combination with P. gingivalis
      lipopolysaccharide (LPS) on expression of the pro-inflammatory cytokines
      interleukin (IL)-6 and IL-8 in periodontal fibroblasts and the underlying
      mechanism of action. MATERIAL AND METHODS: Gingival fibroblasts (GFs) and
      periodontal ligament cells (PDLCs) were treated with different concentrations of
      the H2S donor NaHS in the presence/absence of P. gingivalis LPS for different
      time periods. Expression of IL-6 and IL-8 was detected by real-time PCR and
      ELISA. The activity of nuclear factor-kappa B (NF-kappaB) signalling was
      investigated using western blotting, EMSA and pathway blockade assays. RESULTS:
      Real-time PCR and ELISA results showed that H2S not only upregulated expression
      of IL-6 and IL-8 at mRNA and protein levels in a dose- and time-dependent manner,
      but also aggravated P. gingivalis LPS-induced expression of IL-6 and IL-8 in GFs
      and PDLCs. Western blotting and EMSA showed that NF-kappaB signalling was
      activated by NaHS, P. gingivalis LPS, and both, which was in accordance with the
      expression levels of IL-6 and IL-8 in GFs and PDLCs. These results were confirmed
      using a NF-kappaB pathway blockade assay. CONCLUSIONS: H2S synergistically
      upregulated P. gingivalis LPS-induced expression of IL-6 and IL-8 in GFs and
      PDLCs via activation of NF-kappaB signalling, which could promote the development
      of periodontitis.

PMID- 24927334
TI  - Catalytic effect of water, formic acid, or sulfuric acid on the reaction of
      formaldehyde with OH radicals.
AB  - In this paper, for the hydrogen abstraction reaction of HCHO by OH radicals
      assisted by water, formic acid, or sulfur acid, the possible reaction mechanisms
      and kinetics have been investigated theoretically using quantum chemistry methods
      and transition-state theory. The potential energy surfaces calculated at the
      CCSD(T)/6-311++G(df,pd)//MP2(full)/6-311++G(df,pd) levels of theory reveal that,
      due to the formation of strong hydrogen bond(s), the relative energies of the
      transition states involving catalyst are significantly reduced compared to that
      reaction without catalyst. However, the kinetics calculations show that the rate
      constants are smaller by about 3, 9, or 10 orders of magnitude for water, formic
      acid, or sulfur acid assisted reactions than that uncatalyzed reaction,
      respectively. Consequently, none of the water, formic acid, or sulfur acid can
      accelerate the title reaction in the atmosphere. 

PMID- 24927332
TI  - MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of
      differential expression across cancer cell line proteomes.
AB  - Multiplexed quantitation via isobaric chemical tags (e.g., tandem mass tags (TMT)
      and isobaric tags for relative and absolute quantitation (iTRAQ)) has the
      potential to revolutionize quantitative proteomics. However, until recently the
      utility of these tags was questionable due to reporter ion ratio distortion
      resulting from fragmentation of coisolated interfering species. These interfering
      signals can be negated through additional gas-phase manipulations (e.g., MS/MS/MS
      (MS3) and proton-transfer reactions (PTR)). These methods, however, have a
      significant sensitivity penalty. Using isolation waveforms with multiple
      frequency notches (i.e., synchronous precursor selection, SPS), we coisolated and
      cofragmented multiple MS2 fragment ions, thereby increasing the number of
      reporter ions in the MS3 spectrum 10-fold over the standard MS3 method (i.e.,
      MultiNotch MS3). By increasing the reporter ion signals, this method improves the
      dynamic range of reporter ion quantitation, reduces reporter ion signal variance,
      and ultimately produces more high-quality quantitative measurements. To
      demonstrate utility, we analyzed biological triplicates of eight colon cancer
      cell lines using the MultiNotch MS3 method. Across all the replicates we
      quantified 8,378 proteins in union and 6,168 proteins in common. Taking into
      account that each of these quantified proteins contains eight distinct cell-line
      measurements, this data set encompasses 174,704 quantitative ratios each measured
      in triplicate across the biological replicates. Herein, we demonstrate that the
      MultiNotch MS3 method uniquely combines multiplexing capacity with quantitative
      sensitivity and accuracy, drastically increasing the informational value
      obtainable from proteomic experiments.

PMID- 24927333
TI  - Anchorage-independent growth of Ewing sarcoma cells under serum-free conditions
      is not associated with stem-cell like phenotype and function.
AB  - Novel treatment strategies for Ewing sarcoma aim to eliminate residual tumor
      cells that have maintained the capacity to reinitiate tumor growth after
      intensive conventional therapy. Preclinical models that more closely mimic in
      vivo tumor growth than standard monolayer cultures are needed. Sphere formation
      under anchorage-independent, serum-free conditions has been proposed to enrich
      for cells with tumor-initiating, stem cell-like properties in various solid
      cancers. In the present study, we assessed the phenotype and functional stem cell
      characteristics of Ewing sarcoma spheres. Spheres were generated under serum-free
      culture conditions from four Ewing sarcoma cell lines and four relapse tumor
      biopsies. Standard monolayer cultures were established as controls. Median levels
      of surface expression of the Ewing sarcoma marker CD99 as well as the supposed
      stem cell marker CD133 and the neural crest marker CD57 were comparable between
      spheres and monolayers. Ewing sarcoma spheres from individual tumors failed to
      continuously self-renew by secondary sphere formation. They contained variable
      proportions of side populations (SPs). Sphere culture did not enhance the in vivo
      tumorigenicity of Ewing sarcoma cells in a murine xenograft model. We conclude
      that sphere formation under serum-free conditions is not a reliable tool to
      enrich for cells with stem cell characteristics in Ewing sarcoma. By mimicking
      the anchorage-independent, multicellular growth of Ewing sarcoma micrometastases,
      in vitro sphere growth may still add value as a preclinical tool to evaluate the
      efficacy of novel therapeutics.

PMID- 24927335
TI  - World Health Day 2014: an opportunity to promote research on vectors & vector
      borne diseases.

PMID- 24927336
TI  - A brief history of vaccines & vaccination in India.
AB  - The challenges faced in delivering lifesaving vaccines to the targeted
      beneficiaries need to be addressed from the existing knowledge and learning from
      the past. This review documents the history of vaccines and vaccination in India
      with an objective to derive lessons for policy direction to expand the benefits
      of vaccination in the country. A brief historical perspective on smallpox disease
      and preventive efforts since antiquity is followed by an overview of 19 th
      century efforts to replace variolation by vaccination, setting up of a few
      vaccine institutes, cholera vaccine trial and the discovery of plague vaccine.
      The early twentieth century witnessed the challenges in expansion of smallpox
      vaccination, typhoid vaccine trial in Indian army personnel, and setting up of
      vaccine institutes in almost each of the then Indian States. In the post
      independence period, the BCG vaccine laboratory and other national institutes
      were established; a number of private vaccine manufacturers came up, besides the
      continuation of smallpox eradication effort till the country became smallpox free
      in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal
      Immunization Programme (UIP) (1985) were launched in India. The intervening
      events since UIP till India being declared non-endemic for poliomyelitis in 2012
      have been described. Though the preventive efforts from diseases were practiced
      in India, the reluctance, opposition and a slow acceptance of vaccination have
      been the characteristic of vaccination history in the country. The operational
      challenges keep the coverage inequitable in the country. The lessons from the
      past events have been analysed and interpreted to guide immunization efforts. 

PMID- 24927337
TI  - Role of neural modulation in the pathophysiology of atrial fibrillation.
AB  - Atrial-fibrillation (AF) is the most common clinically encountered arrhythmia
      affecting over 1 per cent of population in the United States and its prevalence
      seems to be moving only in forward direction. A recent systemic review estimates
      global prevalence of AF to be 596.2 and 373.1 per 100,000 population in males and
      females respectively. Multiple mechanisms have been put forward in the
      pathogenesis of AF, however; multiple wavelet hypothesis is the most accepted
      theory so far. Similar to the conduction system of the heart, a neural network
      exists which surrounds the heart and plays an important role in formation of the
      substrate of AF and when a trigger is originated, usually from pulmonary vein
      sleeves, AF occurs. This neural network includes ganglionated plexi (GP) located
      adjacent to pulmonary vein ostia which are under control of higher centers in
      normal people. When these GP become hyperactive owing to loss of inhibition from
      higher centers e.g. in elderly, AF can occur. We can control these hyperactive GP
      either by stimulating higher centers and their connections, e.g. vagus nerve
      stimulation or simply by ablating these GP. This review provides detailed
      information about the different proposed mechanisms underlying AF, the exact role
      of autonomic neural tone in the pathogenesis of AF and the possible role of
      neural modulation in the treatment of AF. 

PMID- 24927338
TI  - Tobacco cessation outcomes in a cohort of patients attending a chest medicine
      outpatient clinic in Bangalore city, southern India.
AB  - BACKGROUND & OBJECTIVES: Nicotine dependence is a widely prevalent and harmful
      chronic addictive disorder. Quitting tobacco use is however, uncommon in India.
      We present long-term treatment outcomes of out-patient, tobacco cessation
      treatments from a specialty clinic setting in southern India. METHODS: Patients
      seen in a tobacco cessation clinic were characterized for tobacco use, nicotine
      dependence and motivation for quitting and offered pharmacologic/non
      pharmacologic treatment. They were subsequently contacted telephonically at a
      mean (+/-standard deviation) of 24 (+/-9.1) months to assess tobacco cessation
      outcome defined as 'point prevalence of 1-month abstinence' by self-reporting.
      RESULTS: The mean age of participants was 48.0 +/-14.0 yr. Tobacco use
      distribution was: beedis only (22%), cigarettes only (49%), beedis and cigarettes
      (18%), chewing only (2%), and smoking and chewing (9%). Two-thirds had high level
      of nicotine dependence. Of the 189 patients enrolled, only 15 per cent attended
      follow up clinics. Only 106 (56%) patients were successfully contacted
      telephonically and 83 (44%) were lost to follow up. Self-reported point
      prevalence abstinence was 5 per cent by 'intent-to-treat' analysis and 10 per
      cent by 'responder' analysis. Two clinical parameters - high level of nicotine
      dependence [estimated by the heaviness of smoking index (HSI)] and the absence of
      vascular or other chronic disease were found to be associated with successful
      quitting; these were however, not significant on multivariate analysis.
      INTERPRETATION & CONCLUSIONS: Our study has identified low quit-rates in a cohort
      of patients attending a hospital-based tobacco cessation clinic. In the absence
      of clear-cut predictors of cessation with low quit-rates, there should be
      continued efforts to improve cessation outcomes and identify predictors for
      action.

PMID- 24927339
TI  - Physical state & copy number of high risk human papillomavirus type 16 DNA in
      progression of cervical cancer.
AB  - BACKGROUND & OBJECTIVES: High-risk human papilloma virus (HR-HPV) infection and
      its integration in host genome is a key event in malignant transformation of
      cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to
      analyze if viral load and physical state of the virus correlated with each other
      in the absence of other confounding variables and examined their potential as
      predictors of progressive cervical lesions. METHODS: Both, viral load and
      integration status of HPV16 were determined by real time URR PCR and estimation
      of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected
      cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30) and
      high grade (HSIL, 30), and invasive carcinoma, (squamous cell carcinoma SCC, 70)
      cases. RESULTS: Investigation of DNA samples revealed a gradual increase in HPV16
      viral load over several magnitudes and increased frequency of integration from
      LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions
      in monotypic HPV16-infected cervical tissues. In a substantial number of
      precancer (11/60) and cancer cases (29/70), HPV16 was detected in concomitant
      mixed form. The concomitant form of HPV16 genome carried significantly higher
      viral load. INTERPRETATION & CONCLUSIONS: Overall, viral load and integration
      increased with disease severity and could be useful biomarkers in disease
      progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.

PMID- 24927341
TI  - Bioevaluation of (125) I Ocu-Prosta seeds for application in prostate cancer
      brachytherapy.
AB  - BACKGROUND & OBJECTIVES: In recent years, brachytherapy involving permanent
      radioactive seed implantation has emerged as an effective modality for the
      management of cancer of prostate. 125 I-Ocu-Prosta seeds were indigenously
      developed and studies were carried out to assess the safety of the indigenously
      developed 125 I-Ocu-Prosta seeds for treatment of prostate cancer. METHODS:
      Animal experiments were performed to assess the likelihood of in vivo release of
      125 I from radioactive seeds and migration of seeds implanted in the prostate
      gland of the rabbit. In vivo release of 125 I activity was monitored by serial
      blood sampling from the auricular vein and subsequent measurement of 125 I
      activity. Serial computed tomography (CT) scans were done at regular intervals
      till 6 months post implant to assess the physical migration of the seeds.
      RESULTS: The laser welded seeds maintained their hermeticity and prevented the in
      vivo release of 125 I activity into the blood as no radioactivity was detected
      during follow up blood measurements. Our study showed that the miniature 125 I
      seeds were clearly resolved in CT images. Seeds remained within the prostate
      gland during the entire study period. Moreover, the seed displacement was minimal
      even within the prostate gland. INTERPRETATION & CONCLUSIONS: Our findings have
      demonstrated that indigenously developed 125 I-Ocu-Prosta seeds may be suitable
      for application in treatment of prostate cancer.

PMID- 24927340
TI  - An approach for conjugation of (177) Lu- DOTA-SCN- Rituximab (BioSim) & its
      evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins
      lymphoma patients.
AB  - BACKGROUND & OBJECTIVES: The prerequisite of radioimmunotherapy is stable binding
      of a radionuclide to monoclonal antibodies, which are specific to the tumour
      associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of
      the tumour cells, making it a suitable target for therapeutic radioactive
      monoclonal antibodies. In the present study, the immunoconjugate of biosimilar
      Rituximab (RedituxTM) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and
      radiolabelled with Lutetium-177 followed by quality control procedures. METHODS:
      Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and
      incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was
      evaluated by determining the number of chelators per antibody molecule. This
      conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The
      quality control parameters like pH, clarity, radiochemical purity, in vitro
      stability and sterility were studied. Immunoreactivity of 177 Lu-DOTA-Rituximab
      (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after
      stringent quality assurance was injected in three patients and the
      biodistribution profile was analysed. RESULTS: An average of 4.25 +/- 1.04 p-SCN
      Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab
      (BioSim).The radiochemical purity of the labelled antibody was > 95 per cent with
      preserved affinity for CD20 antigen. The final preparation was stable up to about
      120 h when tested under different conditions. A favourable biodistribution
      profile was observed with liver showing the maximum uptake of the RIC.
      INTERPRETATION & CONCLUSIONS: A favourable radiochemical purity, stability and
      biodistribution of the radiolabelled immunoconjugate indicate that clinical
      trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody
      Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma
      can be considered.

PMID- 24927342
TI  - Downregulated inhibitor of growth 3 (ING3) expression during colorectal
      carcinogenesis.
AB  - BACKGROUND & OBJECTIVES: ING3 (inhibitor of growth protein 3) overexpression
      decreased S-phase cell population and colony-forming efficiency, and induced
      apoptosis at a p53-mediated manner. The aim of this study was to investigate the
      clinicopathological and prognostic significance of ING3 expression in colorectal
      carcinogenesis and subsequent progression. METHODS: ING3 expression was examined
      by immunohistochemistry on tissue microarray containing colorectal non-neoplastic
      mucosa (NNM), adenoma and adenocarcinoma. Colorectal carcinoma tissue and cell
      lines were studied for ING3 expression by Western blot or RT-PCR. RESULTS: ING3
      mRNA was differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT
      29, KM-12, SW480, SW620 and WiDr cells. Carcinomas showed significantly lower
      ING3 expression than matched NNM at mRNA level (P< 0.05), but not at protein
      level. Immunohistochemically, ING3 expression was significantly decreased from
      NNM, adenoma to adenocarcinoma (P< 0.05). ING3 expression was not correlated with
      age, sex, tumour size, depth of invasion, lymphatic or venous invasion, lymph
      node metastasis, tumour- node- metastasis staging or differentiation. Kaplan
      Meier analysis indicated that ING3 protein expression was not associated the
      prognosis of the patients with colorectal carcinoma (P< 0.05). INTERPRETATION &
      CONCLUSIONS: Our study showed that downregulated ING3 expression might play an
      important role in colorectal adenoma-adenocarcinoma sequence. Further studies are
      required to understand the mechanism.

PMID- 24927343
TI  - Role of oxidative stress & antioxidant defence in ulcerative colitis patients
      from north India.
AB  - BACKGROUND & OBJECTIVES: Oxidative stress contributes to severity of ulcerative
      colitis (UC) but the status of erythrocyte antioxidant defence remains unknown.
      The present study was aimed to study the role of oxidative stress and antioxidant
      levels in erythrocytes of UC patients from north India. METHODS: A total of 81
      adult UC patients and 85 age and sex matched apparently healthy controls were
      included in this study. Levels of lipid peroxidation (LPO), reduced glutathione
      (GSH), catalase and superoxide dismutase (SOD) were measured in erythrocytes.
      RESULTS: Mean age of UC patients was 43.5 yr (range 18-64 yr) while in the
      control group this was 45.3 yr (range 20-64 yr). LPO, catalase and SOD levels in
      UC patients were significantly increased (P< 0.05) compared to healthy controls,
      while GSH levels in UC patients were significantly decreased (P< 0.05) compared
      to healthy controls Ulcerative colitis activity score (UCAI) was 157.4+/-27.6 in
      UC patients. INTERPRETATION & CONCLUSIONS: Increased levels of LPO, SOD, catalase
      and a decreased level of GSH represent that oxidative stress plays a significant
      role in pathophysiology of UC. Further, the levels of LPO, GSH, catalase and SOD
      remained same during different UCAI.

PMID- 24927344
TI  - CYP4F2 1347 G > A & GGCX 12970 C > G polymorphisms: frequency in north Indians &
      their effect on dosing of acenocoumarol oral anticoagulant.
AB  - BACKGROUND & OBJECTIVES: CYP4F2 and gamma-glutamyl carboxylase (GGCX) have small
      but significant roles in the maintenance dose of coumarinic oral anticoagulants
      (COAs). CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms have been used in
      the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese
      populations. India has a large population with multiple ethnic groups but there
      are no reports about the frequencies of these polymorphisms in north Indians. In
      the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G
      > A and GGCX 12970 C > G polymorphisms in a north Indian population and relate
      these to daily maintenance drug dose requirements of COA. METHODS: CYP4F2 1347 G
      > A and GGCX 12970 C > G polymorphisms were genotyped by polymerase chain
      reaction - restriction fragment length polymorphism (PCR-RFLP) protocols and
      Taqman SNP discrimination assays in healthy volunteers (n=102) and patients
      (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve
      replacement surgery. RESULTS: In healthy volunteers, the allele frequencies for
      CYP4F2 1347 G > A and GGCX 12970 C > G were 43.14 and 1.43 per cent,
      respectively. No significant differences in mean weight normalized doses of
      acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic
      regression analysis revealed no significant association of any of the genotypes
      or alleles with the dosing phenotypes for both the SNPs. INTERPRETATION &
      CONCLUSIONS: We report distinct frequencies of CYP4F2 1347 G > A and GGCX 12970 C
      > G polymorphisms in north Indians but these polymorphisms did not have
      significant bearing on maintenance dose of acenocoumarol oral anticoagulant in
      cardiac valve replacement patients.

PMID- 24927345
TI  - Blood count in new onset atrial fibrillation after acute myocardial infarction -
      a hypothesis generating study.
AB  - BACKGROUND & OBJECTIVES: Atrial fibrillation (AF) is a common complication after
      acute myocardial infarction (AMI) and associated with increased morbidity and
      mortality. Previous studies identified high white and red blood cell count as
      potential risk factors for new onset AF. The objective of this retrospective,
      nested case-control study was to examine the association of different parameters
      of the blood count with the development of new onset of AF after AMI. METHODS: A
      total of 66 consecutive patients with new onset AF after AMI and 132 sex and age
      matched controls were enrolled into the study and analyzed whether parameters of
      the blood count, including leukocytes, platelets, haemoglobin, haematocrit or
      erythrocyte count, are associated with the occurrence of AF after AMI. All AMI
      patients had undergone coronary angiography. RESULTS: Patients with post-AMI AF
      displayed significantly higher levels of haemoglobin (14.2 g/dl, IQR 12.4-15 vs.
      12.9 g/dl, IQR 11.7-13.8; P< 0.001), haematocrit (41.7 %, IQR 36.6-44.3 vs. 38.7
      %, IQR 34.7-41.5; P 0.0015), and erythrocyte count (4.6 T/l, IQR 4.1-5 vs. 4.2
      T/l, IQR 3.9-4.65; P< 0.001). In the unadjusted and adjusted logistic regression
      analysis, the blood parameters most strongly associated with the outcome were
      serum haemoglobin (crude OR 2.20, 95% CI 1.40- 3.47, P 0.001; adjusted OR 3.82,
      95% CI 1.71- 8.54, P 0.001) and erythrocyte count (crude OR 2.10, 95% CI 1.36
      3.22, P 0.001; adjusted OR 3.79, 95% CI 1.73- 8.33, P 0.001), whereas haematocrit
      did not reach statistical significance. INTERPRETATION & CONCLUSIONS: This study
      shows a significant independent association between serum haemoglobin,
      haematocrit, erythrocyte count and occurrence of AF after AMI. However, the
      pathophysiologic mechanism underlying these associations and its potential
      clinical applicability need to be further elucidated.

PMID- 24927346
TI  - Pasteurization of bone for tumour eradication prior to reimplantation - an in
      vitro & pre-clinical efficacy study.
AB  - BACKGROUND & OBJECTIVES: In current era of limb-salvage therapy, pasteurization
      of bone sarcomas is receiving growing attention as a potential extracorporeal
      treatment and cost-effective alternative to allografts and radiation before
      surgical reimplantation. Detailed in vitro and in vivo pre-clinical study to
      evaluate efficacy of pasteurization to eradicate malignant cells has not been
      reported yet. The present study was carried out to assess the efficacy of
      pasteurization to kill tumour cells both in vitro and in vivo. METHODS:
      Surgically resected specimens of osteosarcomas (n=4) were cut into equal halves
      and one section was pasteurized by heating at 60 degrees C to 65 degrees C for 40
      min. Paired samples before and after pasteurization were studied in vitro for DNA
      ploidy, evaluation of histological change and elimination of mitotic activity.
      These tissues were transplanted in immune-deficient NOD-SCID mice to evaluate
      effect on tumour-generating ability, presence of human nuclei, osteopontin and
      cytokine/chemokines released in tumour-transplanted mice. RESULTS: Non
      pasteurized tumour samples had viable tumour cells which exhibited significant
      growth in culture, increased proliferative ability and clonogenic potential while
      respective pasteurized tumour tissues did not grow in culture and did not exhibit
      clonogenicity. Flow cytometry revealed that propidium iodide positive dead cells
      increased significantly (P< 0.01) post pasteurization. Seven of 12 non
      pasteurized tumour transplanted mice demonstrated tumour-forming ability as
      against 0 of 12 in pasteurized tumour transplanted mice. Solid tumour xenografts
      exhibited strong expression of anti-human nuclei and osteopontin by
      immunohistochemistry as well as secretary human interluekin-6 (IL-6) while
      pasteurized mice failed to express these markers. INTERPRETATION & CONCLUSIONS:
      This study has provided a basis to establish pasteurization as being efficacious
      in ensuring tumour eradication from resected bone tumour specimens. Pasteurized
      tumour bearing bone can thus safely be used to reconstruct large defects after
      tumour resection.

PMID- 24927347
TI  - Age related secretary pattern of growth hormone, insulin-like growth factor-I &
      insulin-like growth factor binding protein-3 in postmenopausal women.
AB  - BACKGROUND & OBJECTIVES: After menopause in women, loss of bone density increases
      rapidly with estrogen deficiency. Evidence has revealed that this deficiency may
      be directly correlated with growth hormone (GH) level declining with age. The
      present study was designed to evaluate the age dependant patterns of GH, insulin
      like growth factor-1 (IGF1-1) and insulin-like growth factor binding protein-3
      (IGFBP-3) endogenous secretion in postmenopausal women. METHODS: During this
      prospective study in a 12-month period, 150 postmenopausal women were enrolled
      who were referred to the densitometry unit of bone research centre of Tabriz
      University of Medical Sciences for assessing bone mineral density. Serum levels
      of basal and clonidine stimulated GH were measured using radioimmunoassay while
      IGF-1 and IGFBP-3 were measured by ELISA. Post stimulation over 3 to 6 fold
      increase in GH over the baseline level was considered normal response and less
      increase was considered abnormal. RESULTS: There were no significant differences
      in the mean levels of GH0, GH60 and GH90 in different age groups of
      postmenopausal women. No significant difference in the mean IGFBP-3 and IGF-1
      levels was seen in different age groups of postmenopausal women. The number of
      postmenopausal women with abnormal response to stimulation by clonidine in 61-70
      and > 70 yr age groups was higher than in other groups (P< 0.05). INTERPRETATION
      & CONCLUSIONS: Despite the higher rate of abnormal response to stimulation by
      clonidine in women aged more than 60 yr, the current study showed no significant
      correlation between age, and the basal and stimulated GH secretion rate and serum
      levels of IGF-1 and IGFBP-3 in postmenopausal women.

PMID- 24927348
TI  - Covalent immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase
      & horseradish peroxidase onto plasticized polyvinyl chloride (PVC) strip & its
      application in serum triglyceride determination.
AB  - BACKGROUND & OBJECTIVES: Reusable biostrip consisting enzymes immobilized onto
      alkylamine glass beads affixed on plasticized PVC strip for determination of
      triglyceride (TG) suffers from high cost of beads and their detachments during
      washings for reuse, leading to loss of activity. The purpose of this study was to
      develop a cheaper and stable biostrip for investigation of TG levels in serum.
      METHODS: A reusable enzyme-strip was prepared for TG determination by co
      immobilizing lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and
      peroxidase (HRP) directly onto plasticized polyvinyl chloride (PVC) strip through
      glutaraldehyde coupling. The method was evaluated by studying its recovery,
      precision and reusability. RESULTS: The enzyme-strip showed optimum activity at
      pH 7.0, 35 o C and a linear relationship between its activity and triolein
      concentration in the range 0.1 to 15 mM. The strip was used for determination of
      serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of
      added triolein was 96 per cent. Within and between batch coefficients of
      variation (CV) were 2.2 and 3.7 per cent, respectively. A good correlation
      (r=0.99) was found between TG values by standard enzymic colrimetric method
      employing free enzymes and the present method. The strip lost 50 per cent of its
      initial activity after its 200 uses during the span of 100 days, when stored at 4
      o C. INTERPRETATION & CONCLUSIONS: The nitrating acidic treatment of plasticized
      PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic
      colourimetric determination of serum TG. The strip provided 200 reuses of enzymes
      with only 50 per cent loss of its initial activity. The method could be used for
      preparation of other enzyme strips also.

PMID- 24927349
TI  - Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on
      brain cerebrum, liver & kidney in rats.
AB  - BACKGROUND & OBJECTIVES: Sidh Makardhwaj (SM) is a mercury based Ayurvedic
      formulation used in rheumatoid arthritis and neurological disorders. However,
      toxicity concerns due to mercury content are often raised. Therefore, the present
      study was carried out to evaluate the effect of SM on brain cerebrum, liver and
      kidney in rats. METHODS: Graded doses of SM (10, 50, 100 mg/kg), mercuric
      chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats
      for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using
      Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and
      kidney function tests were done on day 28. Animals were sacrificed and brain
      cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced
      glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of
      mercury in brain cerebrum, liver and kidney were estimated and histopathology of
      these tissues was also performed. RESULTS: SM in the doses used did not cause
      significant change in neurobehavioural parameters, brain cerebrum AChE activity,
      liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function
      tests as compared to control. The levels of mercury in brain cerebrum, liver, and
      kidney were found to be raised in dose dependent manner. However, the levels of
      MDA and GSH in these tissues did not show significant changes at doses of 10 and
      50 mg/kg. Also, there was no histopathological change in cytoarchitecture of
      brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg.
      INTERPRETATION & CONCLUSIONS: The findings of the present study suggest that Sidh
      Makardhwaj upto five times the equivalent human dose administered for 28 days did
      not show any toxicological effects on rat brain cerebrum, liver and kidney.

PMID- 24927350
TI  - Effect of active immunization against angiotensin II type 1 (AT1) receptor on
      hypertension & arterial remodelling in spontaneously hypertensive rats (SHR).
AB  - BACKGROUND & OBJECTIVES: a0 ngiotensin II receptor type 1 (AT1) is known to be
      involved in the pathogenesis of hypertension. t0 his study was undertaken to
      explore the effect of active immunization against AT1 receptor on blood pressure
      and small artery remodelling in spontaneously hypertensive rat (SHR). METHODS:
      Male SHR and Wistar rats aged two months were actively immunized with different
      peptides (ATR12185??ATR10014 and ATR12181) corresponding to particular sequences
      of rat AT1 receptor, while another SHR group was given losartan (10 mg/kg/day)
      orally once a day. Anti-AT1 receptor antibodies were detected by ELISA and blood
      pressure was measured. The effect of the antibodies on the artery and vascular
      smooth muscle cells (VSMCs) proliferation was studied. RESULTS: all immunized
      animals produced antibodies against the particular peptides. The systolic blood
      pressure was decreased in the SHR immunized with peptide-ATR12181 compared with
      the control. However, no changes were observed in the SHR immunized with other
      two peptides. The Wistar rats immunized with the three peptides did not show any
      changes in blood pressure. The media/lumen area ratio of the mesenteric artery
      was reduced in SHR immunized with ATR12181 and similar to that of the SHR treated
      with losartan. The antibody from SHR immunized with ATR12181 had no effect on the
      proliferation of VSMC. But it could inhibit the proliferation caused by
      angiotensin II and its effect at the titre of 1:40 was similar to that of 1umol/l
      losartan. INTERPRETATION & CONCLUSIONS: Our findings demonstrated that the
      antibody from SHR immunized with ATR12181 had the effect of reducing blood
      pressure and target organ protection similar to losartan. Active immunization
      against AT1 receptor may be a promising strategy in future for the treatment of
      hypertension.

PMID- 24927351
TI  - Phenotypic identification & molecular detection of bla (ndm-1) gene in multidrug
      resistant Gram-negative bacilli in a tertiary care centre.
AB  - BACKGROUND & OBJECTIVES: Carbapenemase-producing Enterobacteriaceae isolates have
      been increasingly identified worldwide. Though molecular data regarding New Delhi
      metallo-beta-lactamase-1 (NDM-1) producers are available, data regarding their
      rate of infection in a hospital setting and percentage among different clinical
      isolates are scarce. Hence, this study was undertaken to determine the occurrence
      of bla NDM-1 gene among clinical isolates of multidrug resistant Gram-negative
      bacilli (MDRGNB) in a tertiary care centre in Bangalore, Karnataka, India.
      METHODS: A total of 74 MDRGNB isolates were studied. These were screened for MBL
      production by phenotypic assays such as double disk synergy test (DDST) and
      Modified Hodge's test (MHT). PCR was performed for the molecular detection of the
      gene and antibiograms were confirmed by automated bacteriology system. RESULTS:
      Of the 74 MDRGNB isolates, 34 were positive for bla NDM-1 gene. All isolates were
      resistant to aztreonam and two isolates were resistant to tigecycline. Complete
      resistance to the tested carbapenems was seen in 28 (82.35%) of the positive
      isolates whereas variable carbapenem resistance was seen in six (17.64%) of the
      positive clinical isolates. Of the total 34 PCR positive isolates, 33 (97.05%)
      NDM-1 producers were identified by DDST and 26 (76.47%) by MHT as producers of
      MBL. INTERPRETATION & CONCLUSIONS: A high percentage of plasmid encoded NDM was
      noted in MDRGNB. Phenotypic and molecular screening should be employed along with
      routine antimicrobial susceptibility testing to reflect the true number of
      metallo-beta-lactamase producers.

PMID- 24927352
TI  - Detection & characterization of necrotoxin producing Escherichia coli (NTEC) from
      patients with urinary tract infection (UTI).
AB  - BACKGROUND & OBJECTIVES: Urinary tract infections (UTI) are a serious health
      problem affecting millions of people each year. Although appreciable work on
      various aspects of UTI including aetiology per se has been done, information on
      the emerging pathogens like necrotoxigenic Escherichia coli (NTEC) is largely
      lacking in India. In the present study E. coli isolates from patients with
      urinary tract infection from northeastern India were investigated for detection
      and characterization of NTEC. METHODS: E. coli isolated and identified from urine
      samples of patients with UTI were serotyped. Antibiogram was determined by disc
      diffusion test. Plasmid profile was also determined. Virulence genes of NTEC
      (cnf1, cnf2, pap, aer, sfa, hly, afa) were detected by PCR assay. E.coli isolates
      carrying cnf gene (s) were identified as NTEC. RESULTS: A total of 550 E. coli
      were isolated and tested for the presence of cnf genes. Of these, 84 (15.27%)
      belonged to NTEC. The cnf1 gene was present in 52 (61.9%) isolates, cnf2 in 23
      (27.4%) and 9 (10.7%) carried both cnf1 and cnf2 genes. All the NTEC strains were
      found to harbour the pap and aer genes. Serogroup O4 was found to be the most
      common among the 12 serogroups identified amongst the NTEC isolates. Majority of
      the isolates (96.4%) were sensitive to furazolidone and were highly resistant to
      ampicillin. NTEC were found to harbour different numbers of plasmids (1 to 7). No
      association was observed between the number of plasmids and the antibiotic
      resistance of the isolates. INTERPRETATION & CONCLUSIONS: The results of the
      present study showed that about 15 per cent of E. coli isolates associated with
      UTI belonged to NTEC. More studies need to be done from other parts of the
      country.

PMID- 24927353
TI  - Predictors of quitting behaviour with special reference to nicotine dependence
      among adult tobacco-users in a slum of Burdwan district, West Bengal, India.
AB  - BACKGROUND & OBJECTIVES: Information on predictors of quitting behaviour in adult
      tobacco users is scarce in Indian context. Hence, this study was undertaken to
      assess the intention of tobacco-users towards quitting and its predictors with
      reference to nicotine dependence. METHODS: A community-based observational, cross
      sectional study was conducted on 128 adult tobacco-users (89.8% male) with mean
      age of 41.1 +/- 15.7 yr selected by complete enumeration method. Data were
      collected by interview using pre-designed, pre-tested schedule. Nicotine
      dependence was assessed by Fagerstrphim Test for Nicotine Dependence (FTND)
      questionnaire. RESULT: Of the 128 users, 63.3 per cent had intention to quit.
      Majority of the tobacco users who did not intend to quit belonged to the age
      group of > 40 yr (66.0%), were illiterate (55.3%), started tobacco use at 11 - 15
      yr of age (57.4%), had been using tobacco for 20 yr or more (70.2%), were daily
      tobacco users (91.5%), and highly dependent on nicotine (80.9%). Tobacco users
      having high FTND score and who started tobacco use early in life were 1.83 and
      3.30 times more unintended to quit, respectively. INTERPRETATION & CONCLUSIONS:
      Suitable plan for quitting should be developed depending on the FTND score of an
      individual, the most important determinant of quitting that would be beneficial
      for categorization of the treatment leading to successful quitting.

PMID- 24927354
TI  - Multi-drug resistance in clinical isolates of Gram-negative bacilli in a tertiary
      care hospital of Assam.

PMID- 24927355
TI  - Susceptibility testing of Staphylococaus aureus.

PMID- 24927356
TI  - Potter's syndrome - a fatal constellation of anomalies.

PMID- 24927357
TI  - Queyrat erythroplasia accompanied by bladder cancer in a circumcised male.

PMID- 24927358
TI  - Gated molecular baskets.
AB  - In this review, we describe the construction of gated molecular baskets, discuss
      their mechanism of action in regulating the exchange of guests and illustrate the
      potential of these concave hosts to act as catalysts for controlling chemical
      reactions. Importantly, a number of computational and experimental studies have
      suggested that gated baskets ought to unfold their gates at the rim for
      permitting the passage of guests to/from their inner space. These dynamic hosts
      are therefore offered as useful models for investigating the process of gating in
      artificial systems. Furthermore, gated baskets should permit examining the
      benefit of controlling the rate by which reactants access a gated catalyst for
      promoting chemical reactions occurring in its confined space. 

PMID- 24927359
TI  - Monitoring and assessing the impact of wastewater treatment on release of both
      antibiotic-resistant bacteria and their typical genes in a Chinese municipal
      wastewater treatment plant.
AB  - Wastewater treatment plants (WWTPs) are important hotspots for the spread of
      antibiotic resistance. However, the release and impact factors of both antibiotic
      resistant bacteria and the relevant genes over long periods in WWTPs have rarely
      been investigated. In this study, the fate of bacteria and genes resistant to six
      commonly used antibiotics was assessed over a whole year. In WWTP effluent and
      biosolids, a high prevalence of heterotrophic bacteria resistant to vancomycin,
      cephalexin, sulfadiazine and erythromycin were detected, each with a proportion
      of over 30%. The corresponding genes (vanA, ampC, sulI and ereA) were all
      detected in proportions of (2.2 +/- 0.8) * 10(-10), (6.2 +/- 3.2) * 10(-9), (1.2
      +/- 0.8) * 10(-7) and (7.6 +/- 4.8) * 10(-8), respectively, in the effluent. The
      sampling season imposed considerable influence on the release of all ARB. High
      release loads of most ARB were detected in the spring, while low release loads
      were generally found in the winter. In comparison, the ARG loads changed only
      slightly over various seasons. No statistical relevance was found between all ARB
      abundances and their corresponding genes over the long-term investigation period.
      This inconsistent behavior indicates that bacteria and genes should both be
      considered when exploring resistance characteristics in wastewater. A redundancy
      analysis was adopted to assess the impact of wastewater quality and operational
      conditions on antibiotic resistance. The results indicated that most ARB and ARG
      proportions were positively related to the COD and turbidity of the raw sewage,
      while negatively related to those of the effluent. DO and temperature exhibited
      strong negative relevance to most ARB prevalence.

PMID- 24927360
TI  - The effects of profound hypothermia on pancreas ischemic injury: a new
      experimental model.
AB  - OBJECTIVE: Pancreatic ischemia-reperfusion (IR) has a key role in pancreas
      surgery and transplantation. Most experimental models evaluate the normothermic
      phase of the IR. We proposed a hypothermic model of pancreas IR to evaluate the
      benefic effects of the cold ischemic phase. METHODS: We performed a reproducible
      model of hypothermic pancreatic IR. The ischemia was induced in the pancreatic
      tail portion (1-hour ischemia, 4-hour reperfusion) in 36 Wistar rats. They are
      divided in 3 groups as follows: group 1 (control), sham; group 2, normothermic
      IR; and group 3, hypothermic IR. In group 3, the temperature was maintained as
      close to 4.5 degrees C. After reperfusion, serum amylase and lipase levels,
      inflammatory mediators (tumor necrosis factor alpha, interleukin 6), and pancreas
      histology were evaluated. RESULTS: In pancreatic IR groups, amylase, cytokines,
      and histological damage were significantly increased when compared with group 1.
      In the group 3, we observed a significant decrease in tumor necrosis factor alpha
      (P = 0.004) and interleukin 6 (P = 0.001) when compared with group 2. We did not
      observe significant difference in amylase (P = 0.867), lipase (P = 0.993), and
      histology (P = 0.201). CONCLUSIONS: In our experimental model, we reproduced the
      cold phase of pancreas IR, and the pancreas hypothermia reduced the inflammatory
      mediators after reperfusion.

PMID- 24927361
TI  - Advances in gold nanoparticle-liquid crystal composites.
AB  - We present the advancement in the research of the dispersion of gold
      nanoparticles (GNPs) in thermotropic calamitic liquid crystals. The
      formation/behavior of surface plasmon resonance (SPR) in GNPs is briefly
      described. The uniform dispersion of GNPs into liquid crystals along with two
      important aspects, i.e. tuning of GNP properties by liquid crystal and vice
      versa, are widely discussed. Overall, the article highlights the advances in the
      research into GNP-liquid crystal composites in terms of their scientific and
      technological aspects. 

PMID- 24927362
TI  - Intramolecular redox-active ligand-to-substrate single-electron transfer: radical
      reactivity with a palladium(II) complex.
AB  - Coordination of the redox-active tridentate NNO ligand L(H2) to Pd(II) yields the
      paramagnetic iminobenzosemiquinonato complex 3. Single-electron reduction of 3
      yields diamagnetic amidophenolato complex 4, capable of activating aliphatic
      azide 5. Experimental and computational studies suggest a redox-noninnocent
      pathway wherein the redox-active ligand facilitates intramolecular ligand-to
      substrate single-electron transfer to generate an open-shell singlet "nitrene
      substrate radical, ligand radical", enabling subsequent radical-type C-H
      amination reactivity with Pd(II). 

PMID- 24927363
TI  - Intrahepatic glissonian approach for single-port laparoscopic liver resection.
AB  - BACKGROUND: Minimal access surgery is moving toward reduced size and fewer ports.
      The aim of this article is to describe our experience with the intrahepatic
      Glissonian approach for single-port laparoscopic left lateral sectionectomy.
      SUBJECTS AND METHODS: We have performed this procedure on 8 consecutive patients.
      A transumbilical incision is performed, and a single-incision platform is
      introduced. The operation begins with ultrasound examination of the liver.
      Intrahepatic Glissonian access of the portal pedicle from segments 2 and 3 is
      performed, and the pedicle is divided with a stapler. The liver is transected,
      and the left hepatic vein is divided with a stapler. A surgical specimen is
      retrieved through the single umbilical incision. No drains are left in place.
      RESULTS: The median operative time was 68 minutes, and there was minimal
      bleeding. The median hospital stay was 1 day. Six patients were operated on for
      liver adenoma. There was no morbidity or mortality. During follow-up (median, 12
      months), no patient developed incisional hernia. The cosmetic appearance of the
      incision was excellent in all cases. CONCLUSIONS: Single-port laparoscopic left
      lateral sectionectomy is feasible and can be safely performed in specialized
      centers.

PMID- 24927364
TI  - Redox-neutral alpha-sulfenylation of secondary amines: ring-fused N,S-acetals.
AB  - Secondary amines react with thiosalicylaldehydes in the presence of catalytic
      amounts of acetic acid to generate ring-fused N,S-acetals in redox-neutral
      fashion. A broad range of amines undergo alpha-sulfenylation, including
      challenging substrates such morpholine, thiomorpholine, and piperazines.
      Computational studies employing density functional theory indicate that acetic
      acid reduces the energy barriers of two separate steps, both of which involve
      proton transfer. 

PMID- 24927365
TI  - Complexity and uniqueness of the aromatic profile of smoked and unsmoked Herreno
      cheese.
AB  - In this work, the volatile fraction of unsmoked and smoked Herreno cheese, a type
      of soft cheese from the Canary Islands, has been characterized for the first
      time. In order to evaluate if the position in the smokehouse could influence the
      volatile profile of the smoked variety, cheeses smoked at two different heights
      were studied. The volatile components were extracted by Solid Phase
      Microextraction using a divinylbenzene/carboxen/ polydimethylsiloxane fiber,
      followed by Gas Chromatography/Mass Spectrometry. In total, 228 components were
      detected. The most numerous groups of components in the unsmoked Herreno cheese
      were hydrocarbons, followed by terpenes and sesquiterpenes, whereas acids and
      ketones were the most abundant. It is worth noticing the high number of aldehydes
      and ketones, and the low number of alcohols and esters in this cheese in relation
      to others, as well as the presence of some specific unsaturated hydrocarbons,
      terpenes, sesquiterpenes and nitrogenated derivatives. The smoking process
      enriches the volatile profile of Herreno cheese with ketones and diketones,
      methyl esters, aliphatic and aromatic aldehydes, hydrocarbons, terpenes,
      nitrogenated compounds, and especially with ethers and phenolic derivatives.
      Among these, methylindanones or certain terpenes like alpha-terpinolene, have not
      been detected previously in other types of smoked cheese. Lastly, the results
      obtained suggest a slightly higher smoking degree in the cheeses smoked at a
      greater height. 

PMID- 24927366
TI  - FACE analysis as a fast and reliable methodology to monitor the sulfation and
      total amount of chondroitin sulfate in biological samples of clinical importance.
AB  - Glycosaminoglycans (GAGs) due to their hydrophilic character and high anionic
      charge densities play important roles in various (patho)physiological processes.
      The identification and quantification of GAGs in biological samples and tissues
      could be useful prognostic and diagnostic tools in pathological conditions.
      Despite the noteworthy progress in the development of sensitive and accurate
      methodologies for the determination of GAGs, there is a significant lack in
      methodologies regarding sample preparation and reliable fast analysis methods
      enabling the simultaneous analysis of several biological samples. In this report,
      developed protocols for the isolation of GAGs in biological samples were applied
      to analyze various sulfated chondroitin sulfate- and hyaluronan-derived
      disaccharides using fluorophore-assisted carbohydrate electrophoresis (FACE).
      Applications to biologic samples of clinical importance include blood serum, lens
      capsule tissue and urine. The sample preparation protocol followed by FACE
      analysis allows quantification with an optimal linearity over the concentration
      range 1.0-220.0 ug/mL, affording a limit of quantitation of 50 ng of
      disaccharides. Validation of FACE results was performed by capillary
      electrophoresis and high performance liquid chromatography techniques. 

PMID- 24927367
TI  - Antidepressant-like effects of the ethyl acetate soluble fraction of the root
      bark of Morus alba on the immobility behavior of rats in the forced swim test.
AB  - In this study, the antidepressant-like effects of Morus alba fractions in rats
      were investigated in the forced swim test (FST). Male Wistar rats (9-week-old)
      were administered orally the M. alba ethyl acetate (EtOAc 30 and 100 mg/kg) and
      M. alba n-butanol fractions (n-BuOH 30 and 100 mg/kg) every day for 7 consecutive
      days. On day 7, 1 h after the final administration of the fractions, the rats
      were exposed to the FST. M. alba EtOAc fraction at the dose of 100 mg/kg induced
      a decrease in immobility behavior (p < 0.01) with a concomitant increase in both
      climbing (p < 0.05) and swimming (p < 0.05) behaviors when compared with the
      control group, and M. alba EtOAc fraction at the dose of 100 mg/kg decreased the
      hypothalamic-pituitary-adrenal (HPA) axis response to the stress, as indicated by
      an attenuated corticosterone response and decreased c-fos immunoreactivity in the
      hippocampal and hypothalamic paraventricular nucleus (PVN) region. These findings
      demonstrated that M. alba EtOAc fraction have beneficial effects on depressive
      behaviors and restore both altered c-fos expression and HPA activity. 

PMID- 24927368
TI  - Polymerization degrees, molecular weights and protein-binding affinities of
      condensed tannin fractions from a Leucaena leucocephala hybrid.
AB  - Condensed tannins (CTs) form insoluble complexes with proteins and are able to
      protect them from degradation, which could lead to rumen bypass proteins.
      Depending on their degrees of polymerization (DP) and molecular weights, CT
      fractions vary in their capability to bind proteins. In this study, purified
      condensed tannins (CTs) from a Leucaena leucocephala hybrid were fractionated
      into five different molecular weight fractions. The structures of the CT
      fractions were investigated using 13C-NMR. The DP of the CT fractions were
      determined using a modified vanillin assay and their molecular weights were
      determined using Q-TOF LC-MS. The protein-binding affinities of the respective CT
      fractions were determined using a protein precipitation assay. The DP of the five
      CT fractions (fractions F1-F5) measured by the vanillin assay in acetic acid
      ranged from 4.86 to 1.56. The 13C-NMR results showed that the CT fractions
      possessed monomer unit structural heterogeneity. The number-average molecular
      weights (Mn) of the different fractions were 1265.8, 1028.6, 652.2, 562.2, and
      469.6 for fractions F1, F2, F3, F4, and F5, respectively. The b values
      representing the CT quantities needed to bind half of the maximum precipitable
      bovine serum albumin increased with decreasing molecular weight--from fraction F1
      to fraction F5 with values of 0.216, 0.295, 0.359, 0.425, and 0.460,
      respectively. This indicated that higher molecular weight fractions of CTs from
      L. leucocephala have higher protein-binding affinities than those with lower
      molecular weights.

PMID- 24927369
TI  - Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer
      patients survival.
AB  - The disruption of the circadian timing system (CTS), which rhythmically controls
      cellular metabolism and proliferation, accelerated experimental cancer
      progression. A measure of CTS function in cancer patients could thus provide
      novel prediction information for outcomes, and help to identify novel specific
      therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS
      biomarker, which was monitored using a wrist watch accelerometer for 2 days in
      436 patients with metastatic colorectal cancer. The relative percentage of
      activity in-bed versus out-of-bed (I < O) constituted the tested CTS measure,
      whose prognostic value for overall survival (OS) and progression-free survival
      (PFS) was determined in a pooled analysis of three patient cohorts with different
      treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I <
      O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for
      those with a lower I < O (Log-rank p < 0.001). Multivariate analyses retained
      continuous I < O as a joint predictor of both OS and PFS, with respective hazard
      ratios (HR) of 0.954 (p < 0.001) and 0.970 (p < 0.001) for each 1% increase in I
      < O. HRs had similar values in all the patient subgroups tested. The circadian
      physiology biomarker I < O constitutes a robust and independent quantitative
      predictor of cancer patient outcomes, that can be easily and cost-effectively
      measured during daily living. Interventional studies involving 24-h schedules of
      clock-targeted drugs, light intensity, exercise and/or meals are needed for
      testing the relevance of circadian synchronization for the survival of patients
      with disrupted rhythms.

PMID- 24927370
TI  - Chronotype, gender, and time for sex.
AB  - The study aimed at testing chronotype and gender differences in the time of day
      when humans feel the greatest need for sex and the time of day they actually
      undertake sexual activity. A Polish sample of 565 participants aged between 18
      and 57 was tested. In females, regardless of chronotype, the greatest need for
      sex occurred between 18:00 and 24:00, but a secondary peak appeared only in
      morning types at 6:00-9:00. In males, the greatest need for sex occurred either
      in the morning or evening hours: in evening types at 9:00-12:00 and 18:00-3:00;
      in neither types at 6:00-9:00 and 18:00-24:00; in morning types at 6:00-12:00 and
      18:00-24:00. Considering time of day when subjects were undertaking sexual
      activity most frequently, this appeared between 18:00 and 24:00 for all the
      participants, and prolonged until 3:00 at night in evening type males.
      Morningness preference was more strongly related to the timing of need for sex
      than to the timing of actual sexual activity (r = -0.275 vs. r = -0.174), while
      the timing of desire and the timing of sexual activity were positively, but
      moderately related (r = 0.320).

PMID- 24927371
TI  - Multivariate modular metabolic engineering for pathway and strain optimization.
AB  - Despite the potential in utilizing microbial fermentation for chemical
      production, the field of industrial biotechnology still lacks a standard,
      universally applicable principle for strain optimization. A key challenge has
      been in finding and applying effective ways to address metabolic flux imbalances.
      Strategies based on rational design require significant a priori knowledge and
      often fail to take a holistic view of cellular metabolism. Combinatorial
      approaches enable more global searches but require a high-throughput screen.
      Here, we present the recent advances and promises of a novel approach to
      metabolic pathway and strain optimization called multivariate modular metabolic
      engineering (MMME). In this technique, key enzymes are organized into distinct
      modules and simultaneously varied based on expression to balance flux through a
      pathway. Because of its simplicity and broad applicability, MMME has the
      potential to systematize and revolutionize the field of metabolic engineering and
      industrial biotechnology. 

PMID- 24927372
TI  - One-pot synthesis of metal-carbon nanotubes network hybrids as highly efficient
      catalysts for oxygen evolution reaction of water splitting.
AB  - Oxygen evaluation reaction (OER) is the most important reaction in hydrogen
      production from water splitting. Here we developed metal-carbon nanotubes (M
      CNTs) hybrids with high metal oxide catalyst loading synthesized by arc-discharge
      and chemical vapor deposition (CVD) methods as electrocatalysts for OER in
      alkaline solutions. The M-CNTs hybrids produced by arc-discharge (M-CNTs-Arc) and
      CVD (M-CNTs-CVD) exhibit a core-shell-like structure, in which metal
      nanoparticles (NPs) encapsulated by graphite shells are connected by carbon
      nanotubes (CNTs), forming M-CNTs network hybrids. M-CNTs-Arc has NiCo0.16Fe0.34
      metal core and shows very high activity and superior stability for OER, achieving
      100 A g(-1) at an overpotential (eta) of 0.29 V and 500 A g(-1) at eta = 0.37 V
      in 1 M KOH solution. This is probably the highest activity reported for OER in
      alkaline solutions. The reaction follows the first-order kinetics with respect to
      OH(-) concentration and Tafel slope of 34 mV dec(-1). The results demonstrate a
      highly efficient, scalable, and low-cost one-step synthesis method for developing
      highly active and stable catalysts for electrochemical water splitting in
      alkaline solutions. 

PMID- 24927373
TI  - Nucleolin identified by comparative mass-spectra analysis is a potential marker
      for invasive progression of hepatocellular carcinoma.
AB  - At present, the diagnosis and prognosis of hepatocellular carcinoma (HCC)
      metastasis remains poor. Recently, a number of proteins associated with the
      metastasis and invasion of HCC were identified; however, the effective markers
      require further elucidation. In the current study, a nucleolin expression was
      observed in MHCC97L and HCCLM9 HCC cell lines, with low and high metastatic
      potentials respectively, using comparative proteomics. The data indicated that
      nucleolin expression in the nucleus was significantly higher in HCCLM9 cells, and
      it primarily influenced the migration of HCC cells in vitro. Thus, to the best of
      our knowledge this is the first study to hypothesize that nucleolin may be a
      novel marker for HCC invasive progression.

PMID- 24927374
TI  - Risk of current asthma among adult smokers with respiratory syncytial virus
      illnesses in early life.
AB  - RATIONALE: Risk of subsequent asthma-like symptoms after early-life lower
      respiratory illness (LRI) caused by respiratory syncytial virus (RSV) is
      increased during the first decade of childhood and diminished thereafter by
      adolescence. OBJECTIVES: To determine the relation of early-life RSV-LRI on adult
      asthma-like symptoms and its interactive role with adult smoking. METHODS: A
      total of 1,246 nonselected infants were enrolled at birth and prospectively
      followed. Virologically confirmed RSV-LRIs were assessed during the first 3 years
      of life. At age 22, 24, 26, and 29 years, current asthma and smoking behavior
      were evaluated by questionnaire. Peak flow variability was assessed at age 26 and
      expressed as amplitude % mean. A longitudinal analysis was used to investigate
      the relation of RSV-LRI and active smoking to adult outcomes. MEASUREMENTS AND
      MAIN RESULTS: Neither RSV-LRI nor active smoking were directly associated with
      increased current adult asthma or peak flow variability. However, there was a
      significant interaction between RSV-LRI and active smoking in relation to current
      asthma (P for interaction = 0.004) and peak flow variability (P for interaction =
      0.04). Among subjects with early RSV-LRI, those who actively smoked were 1.7
      times more likely to have current asthma (95% confidence interval, 1.2-2.3; P =
      0.003) and had greater amplitude % mean (10.0% vs. 6.4%; P = 0.02) than
      nonsmokers. Among subjects without early RSV-LRI, there was no difference in
      asthma risk or peak flow variability between active smokers and nonsmokers.
      CONCLUSIONS: Smoking is associated with increased risk of having asthma in young
      adults who had RSV-LRI in early life but not among subjects without these
      illnesses.

PMID- 24927375
TI  - Long-term/bioinert labeling of rat mesenchymal stem cells with PVA-Gd conjugates
      and MRI monitoring of the labeled cell survival after intramuscular
      transplantation.
AB  - Noninvasive in vivo imaging of transplanted stem cells is an effective method to
      clarify the mechanisms involved in stem cell transplantation therapy. We labeled
      rat mesenchymal stem cells (MSCs) with water-soluble magnetic resonance imaging
      (MRI) contrast agent poly(vinyl alcohol)-gadolinium (PVA-Gd) in order to
      ascertain the fate of transplanted MSCs in vivo. PVA-Gd was retained and
      localized in the cytosolic compartment of MSCs for a longer period of time. The
      effect of PVA-Gd labeling on MSC proliferation was much less than that of the
      commercially available contrast agent ProHance, and the labeled MSCs were found
      to have osteoblastic differentiation ability. To study the MSC lifetime in vivo,
      MSCs were seeded and trapped in the cytocompatible three-dimensional porous
      scaffolds of Spongel and transplanted. The MRI signal attributed to MSCs was
      eliminated from the transplanted site in 14 days. Because free PVA-Gd was rapidly
      eliminated from the site, this signal reduction indicated MSC death in the
      transplantation site. The low efficiency of MSC transplantation for ischemic
      tissue may be due to their short lifetime, making it important to develop highly
      effective stem cell transplantation systems that address cell number, injection
      position, and cell formulation (suspension, sheet, and aggregates). Our cell
      survival tracking system would be a very powerful tool to this end and would be
      applicable in clinical cell therapies. 

PMID- 24927376
TI  - Does prone positioning improve oxygenation and reduce mortality in patients with
      acute respiratory distress syndrome?

PMID- 24927377
TI  - Making an accurate diagnosis of chronic hypersensitivity pneumonitis.
AB  - Chronic hypersensitivity pneumonitis (HP) arises from repeated exposure to
      causative antigens. Although HP can be challenging to diagnose, it is important
      to differentiate from idiopathic pulmonary fibrosis and idiopathic nonspecific
      interstitial pneumonia. HP has a unique management approach and portends a unique
      prognosis. The present article summarizes the recent published literature on
      chronic HP and highlights the features that may be helpful in distinguishing it
      from other chronic interstitial lung diseases.

PMID- 24927378
TI  - Imbalance of different types of CD4(+)Foxp3(+) T cells in renal transplant
      recipients.
AB  - AIMS: To determine the number of CD4(+)CD25(-)Foxp3(+), CD4(+)CD25(+)Foxp3(+) and
      CD4(+)CXCR5(+)Foxp3(+) T cells in renal transplant recipients that are
      transplanted stable (TS), or experiencing accelerated rejection (ALR), or acute
      rejection (AR). METHODS: Renal transplantation was conducted in 28 patients with
      end-stage renal failure (ESRF). The number of peripheral CD4(+)CD25(-)Foxp3(+),
      CD4(+)CD25(+)Foxp3(+), or CD4(+)CXCR5(+)Foxp3(+) T cells and the serum levels of
      interleukin-10 (IL-10) were measured in pre- and post-transplant patients and
      these results were compared to 10 healthy controls (HC). Correlation between
      CD4(+)CD25(+)Foxp3(+) and estimated glomerular filtration rate (eGFR),
      CD4(+)CD25(-)Foxp3(+) and serum creatinine (Cr) levels, or Cr and IL-10 levels in
      TS patients was also determined. RESULTS: The number of CD4(+)CD25(-)Foxp3(+) T
      cells was significantly increased in patients with ESRF, as compared to HC.
      Stratification analysis demonstrated that TS patients contained greater numbers
      of CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells, higher levels of
      serum IL-10, and fewer numbers of CD4(+)CD25(-)Foxp3(+) T cells than ESRF
      patients. In contrast, ALR and AR patients contained fewer numbers of
      CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells, greater numbers of
      CD4(+)CD25(-)Foxp3(+) T cells, and lower levels of serum IL-10 than ESRF
      patients. In TS patients, the numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(
      )Foxp3(+) T cells were positively correlated with eGFR and serum Cr levels,
      respectively. CONCLUSION: An imbalance of different types of CD4(+)Foxp3(+) T
      cells might be involved in renal transplant rejection.

PMID- 24927379
TI  - Latest trends in minimally invasive synostosis surgery: a review.
AB  - PURPOSE OF REVIEW: To present the current surgical options for minimally invasive
      surgery for treatment of craniosynostosis. RECENT FINDINGS: Minimally invasive
      procedures are well tolerated treatment options for patients with
      craniosynostosis. Suturectomy and helmet therapy is a treatment option for
      scaphocephaly with minimal blood loss and length of hospital stay. Spring
      mediated cranioplasty is, in addition, a well tolerated and effective treatment
      option for scaphocephaly. SUMMARY: In patients with multiple suture
      craniosynostosis, surgical techniques that utilize spring-assisted surgery can
      provide decreased morbidity with better bone formation made available for a
      second operation. Continued basic science research and clinical studies will
      expand the use and provide further minimally invasive procedures to infants with
      craniosynostosis.

PMID- 24927380
TI  - Trait impulsivity predicts D-KEFS tower test performance in university students.
AB  - The present study examined a widely used self-report index of trait impulsiveness
      in relation to performance on a well-known neuropsychological executive function
      test in 70 university undergraduate students (50 women, 20 men) aged 18 to 24
      years old. Participants completed the Barratt Impulsiveness Scale (BIS-11) and
      the Frontal Systems Behavior Scale (FrSBe), after which they performed the Tower
      Test of the Delis-Kaplan Executive Function System. Hierarchical linear
      regression showed that after controlling for gender, current alcohol consumption,
      age at onset of weekly alcohol use, and FrSBe scores, BIS-11 significantly
      predicted Tower Test Achievement scores, beta = -.44, p < .01. The results
      indicate that self-reported impulsiveness is associated with poorer executive
      cognitive performance even in a sample likely to be characterized by relatively
      high general cognitive functioning (i.e., university students). The results also
      support the role of inhibition as a key aspect of executive task performance.
      Elevated scores on the BIS-11 and FrSBe are known to be linked to risky drinking
      in young adults as confirmed in this sample; however, only BIS-11 predicted Tower
      Test performance.

PMID- 24927381
TI  - Kinetics and mechanism of styrene epoxidation by chlorite: role of chlorine
      dioxide.
AB  - An investigation of the kinetics and mechanism for epoxidation of styrene and
      para-substituted styrenes by chlorite at 25  degrees C in the pH range of 5-6 is
      described. The proposed mechanism in water and water/acetonitrile includes seven
      oxidation states of chlorine (-I, 0, I, II, III, IV, and V) to account for the
      observed kinetics and product distributions. The model provides an unusually
      detailed quantitative mechanism for the complex reactions that occur in mixtures
      of chlorine species and organic substrates, particularly when the strong oxidant
      chlorite is employed. Kinetic control of the reaction is achieved by the addition
      of chlorine dioxide to the reaction mixture, thereby eliminating a substantial
      induction period observed when chlorite is used alone. The epoxidation agent is
      identified as chlorine dioxide, which is continually formed by the reaction of
      chlorite with hypochlorous acid that results from ClO produced by the epoxidation
      reaction. The overall stoichiometry is the result of two competing chain
      reactions in which the reactive intermediate ClO reacts with either chlorine
      dioxide or chlorite ion to produce hypochlorous acid and chlorate or chloride,
      respectively. At high chlorite ion concentrations, HOCl is rapidly eliminated by
      reaction with chlorite, minimizing side reactions between HOCl and Cl2 with the
      starting material. Epoxide selectivity (>90% under optimal conditions) is
      accurately predicted by the kinetic model. The model rate constant for direct
      reaction of styrene with ClO2(aq) to produce epoxide is (1.16 +/- 0.07) * 10(-2)
      M(-1) s(-1) for 60:40 water/acetonitrile with 0.20 M acetate buffer. Rate
      constants for para substituted styrenes (R = -SO3(-), -OMe, -Me, -Cl, -H, and 
      NO2) with ClO2 were determined. The results support the radical
      addition/elimination mechanism originally proposed by Kolar and Lindgren to
      account for the formation of styrene oxide in the reaction of styrene with
      chlorine dioxide. 

PMID- 24927382
TI  - Large-area, transparent, and flexible infrared photodetector fabricated using P-N
      junctions formed by N-doping chemical vapor deposition grown graphene.
AB  - Graphene is a highly promising material for high speed, broadband, and multicolor
      photodetection. Because of its lack of bandgap, individually gated P- and N
      regions are needed to fabricate photodetectors. Here we report a technique for
      making a large-area photodetector on the basis of controllable fabrication of
      graphene P-N junctions. Our selectively doped chemical vapor deposition (CVD)
      graphene photodetector showed a ~5% modulation of conductance under global IR
      irradiation. By comparing devices of various geometries, we identify that both
      the homogeneous and the P-N junction regions contribute competitively to the
      photoresponse. Furthermore, we demonstrate that our two-terminal graphene
      photodetector can be fabricated on both transparent and flexible substrates
      without the need for complex fabrication processes used in electrically gated
      three-terminal devices. This represents the first demonstration of a fully
      transparent and flexible graphene-based IR photodetector that exhibits both good
      photoresponsivity and high bending capability. This simple approach should
      facilitate the development of next generation high-performance IR photodetectors.

PMID- 24927384
TI  - Role of wild bird and rodents in the epidemiology of subclinical salmonellosis in
      finishing pigs.
AB  - Wild birds and rodents may play an important role in the dynamics of subclinical
      pig salmonellosis, either as the introducers of the bacteria into the farm or as
      receptors of an infection already established in the farm. We tried to gain
      further insight into the epidemiology of this infection by studying the
      phenotypic (i.e., serotype and antimicrobial resistance patterns) and molecular
      characteristics of Salmonella strains isolated from samples collected from pigs
      and wildlife captured in the vicinity of pig farms. Salmonella-positive pig fecal
      samples were identified in 56.1% of the 41 farms investigated. Birds shedding
      Salmonella spp. were detected in 21.4% of the farms despite the low numbers of
      birds captured in many farms. Most Salmonella isolates from birds (74%) did not
      show any antimicrobial resistance (AR) pattern and belonged to phage types rarely
      seen in the pig population (U310, DT56, DT137, DT164), supporting the likely
      avian source of infection for most birds. The proportion of farms showing
      Salmonella-infected rodents was higher (46.2%), with Salmonella isolates showing
      a high homology with those likely originated from pigs. Salmonella-positive
      environmental samples were found in >50% of the farms, and the characteristics of
      these Salmonella strains supported the idea of pigs as a major source of
      Salmonella contamination of the farm environment. Dissemination of Salmonella in
      pig farms from areas of high Salmonella prevalence appeared to depend to some
      extent upon rodents and wild birds present in the farm, but the role of rodents
      in its maintenance seemed to be somewhat more relevant than that of birds. In
      conclusion, activities aimed at reducing the contact of these wild species with
      pigs will probably assist in the control of pig salmonellosis. Strict hygienic
      measures should be considered in areas of high prevalence of infection to lower
      the high load of environmental contamination.

PMID- 24927383
TI  - The acute phase of mild traumatic brain injury is characterized by a distance
      dependent neuronal hypoactivity.
AB  - The consequences of mild traumatic brain injury (TBI) on neuronal functionality
      are only now being elucidated. We have now examined the changes in sensory
      encoding in the whisker-recipient barrel cortex and the brain tissue damage in
      the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving
      surgery only (n=5). Injury was induced using the lateral fluid percussion injury
      method, which causes a mixture of focal and diffuse brain injury. Both population
      and single cell neuronal responses evoked by both simple and complex whisker
      stimuli revealed a suppression of activity that decreased with distance from the
      locus of injury both within a hemisphere and across hemispheres, with a greater
      extent of hypoactivity in ipsilateral barrel cortex compared with contralateral
      cortex. This was coupled with an increase in spontaneous output in Layer 5a, but
      only ipsilateral to the injury site. There was also disruption of axonal
      integrity in various regions in the ipsilateral but not contralateral hemisphere.
      These results complement our previous findings after mild diffuse-only TBI
      induced by the weight-drop impact acceleration method where, in the same acute
      post-injury phase, we found a similar depth-dependent hypoactivity in sensory
      cortex. This suggests a common sequelae of events in both diffuse TBI and mixed
      focal/diffuse TBI in the immediate post-injury period that then evolve over time
      to produce different long-term functional outcomes.

PMID- 24927385
TI  - Speciation of methylmercury in market seafood by thermal degradation,
      amalgamation and atomic absorption spectroscopy.
AB  - Sample thermal decomposition followed by mercury amalgamation and atomic
      absorption has been employed for the determination of methylmercury (MeHg) in
      fish. The method involves HBr leaching of MeHg, extraction into toluene, and back
      extraction into an aqueous l-cysteine solution. Preliminary studies were focused
      on the extraction efficiency, losses, contaminations, and species interconversion
      prevention. The limit of detection was 0.018ugg(-1) (dry weight). The intraday
      precision for three replicate analysis at a concentration of 4.2ugg(-1) (dry
      weight) was 3.5 percent, similar to the interday precision according to analysis
      of variance (ANOVA). The accuracy was guaranteed by the use of fortified samples
      involving 83-105 percent recoveries, and certified reference materials TORT-2
      (lobster hepatopancreas) and DORM-3 (dogfish liver), providing 107 and 98 percent
      recovery of certified values. The greenness of the method was also evaluated with
      the analytical eco-scale being obtained a final score of 73 points which means an
      acceptable green analysis. The method was applied to fifty-seven market samples
      of different fish acquired from local markets in several sampling campaigns. The
      content of MeHg found varied between 0.0311 and 1.24ugg(-1) (wet weight), with
      values that involve 33-129 percent of the total mercury content. Some
      considerations about food safety were also done taking into account data about
      Spanish fish consume and Tolerable Weekly Intake (TWI) established for MeHg. 

PMID- 24927386
TI  - Bioconcentration of mercury by mushroom Xerocomus chrysenteron from the spatially
      distinct locations: levels, possible intake and safety.
AB  - Concentrations of mercury were determined in specimens of Red Cracking Bolete
      (Xerocomus chrysenteron) (Bull.) Quel. and overlying soil (0-10cm) collected from
      22 spatially distributed sites in Poland during 1996-2013 to assess the potential
      of this species to bioconcentrate Hg and possible intake by humans. The mean Hg
      concentrations ranged from 80 to 630 for caps and from 28 to 380ng/g dry matter
      (dm) for stipes. Decrease in the potential of this mushroom species to
      bioconcentrate Hg both in caps and stipes was observed when the Hg content in
      soil substratum increased from 15 to 75-94ng/g dm. A maximum median value for
      bioconcentration factor (BCF) of Hg determined for caps was 18 for soil with Hg
      content at 15ng/g dm and decreased to 0.97-3.8 for soils that contained Hg at 37
      94ng/g dm. Caps of X. chrysenteron consumed at a volume of 300g daily in a week
      can yield an exposure amount of Hg at 0.0168-0.1323mg (0.00024 to 0.00189mg/kg
      body mass); these values are well below the provisionally tolerated weekly intake
      (PTWI) for inorganic Hg.

PMID- 24927387
TI  - Biomarkers of environmental stress in gills of ribbed mussel Aulacomya atra atra
      (Nuevo Gulf, Northern Patagonia).
AB  - In this study, we assessed in gills of native ribbed mussels Aulacomya atra atra
      from three sites within Nuevo Gulf (Northern Patagonia) several biomarkers such
      as reactive oxygen species (ROS), lipid radicals (LR), malondialdehyde (MDA),
      superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and
      metallothionein (MT). Furthermore, concentrations of main trace metals (Fe, Al,
      Zn, Cu, Cd and Pb) were quantified in mussel tissue. Results showed significant
      induction of SOD, GST, MT and MDA, as well as, higher concentration of Fe, Al and
      Cd in winter than in summer. The high MDA content measured in mussels from Folias
      Wreck seemed to be caused by the very high levels of Fe that would come from the
      corrosion of the vessel. Mussels from the control site Punta Cuevas presented the
      lowest levels of Cd and the highest of Al in winter. Despite positive
      correlations were found between Al and GST and MT, no spatial differentiation was
      detected in those biomarkers. On the other hand, MT was only related to Al been
      most likely influenced by environmental variables than by the trace metals. It
      has to be highlighted that the relationship detected among water temperature,
      nutrients and antioxidant responses in gills is probably related to the fact that
      this tissue is in direct contact with water and it is sensitive to its
      fluctuations. Taking into account that mussel gill is a tissue actively
      proliferating and the first target of contaminants present in water, so that
      changes in its antioxidant system can provide an earlier warning signal than in
      other tissues. 

PMID- 24927388
TI  - Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme
      activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase
      (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.
AB  - Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on
      enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO),
      catalase (CAT), glutathione-S-transferase (GST) and protein content were measured
      in different tissues of two Indian air-breathing teleosts, Anabas testudineus
      (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days
      under laboratory condition. AChE activity was significantly increased in all the
      investigated tissues of both fish species and maximum elevation was observed in
      brain of H. fossilis, while spinal cord of A. testudineus showed minimum
      increment. Fishes showed significant increase LPO levels in all the tissues;
      highest was observed in gill of A. testudineus but lowest LPO level was observed
      in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST
      activity in liver diminished substantially and minimum was observed in liver of
      A. testudineus. Total protein content showed decreased value in all the tissues,
      maximum reduction was observed in liver and minimum in brain of A. testudineus
      and H. fossilis respectively. The results indicated that Excel Mera 71 caused
      serious alterations in the enzyme activities resulting into severe deterioration
      of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of
      herbicidal toxicity. 

PMID- 24927389
TI  - Phytoplankton blooms: an overlooked marine source of natural endocrine disrupting
      chemicals.
AB  - BACKGROUND: We had previously reported high androgenic and estrogenic activities
      in seawaters in confined clusters close to Singapore. Further investigations
      revealed a hitherto unsuspected link between estrogenic/androgenic activity and
      net phytoplankton count. OBJECTIVE: The primary objective of this study was to
      investigate the cause of a correlation between net phytoplankton and endocrine
      activity, and corroborate this observation, and rule out other possible
      confounding factors. Our secondary objective was to study if these estrogenic
      secretions can impact human health. METHODS: Five species of phytoplankton,
      Gymnodinium catenatum, Prorocentrum minimum, Alexandrium leei, Chattonella
      marina, and Fibrocapsa japonica, were isolated from Singapore waters and mass
      cultured and the cells and culture media screened for estrogenic and androgenic
      activity using human cell-based bioassays. RESULTS: The raphidophytes C. marina
      and F. japonica displayed significant estrogenic activity whilst the
      dinoflagellates G. catenatum and P. minimum displayed significant androgenic
      activity in both the cell extracts and the cell culture media extract.
      CONCLUSIONS: Our data shows that selected phytoplankton isolates are potent
      secretors of estrogenic and androgenic substances, which are potential endocrine
      disrupting chemicals (EDCs). As the harmful nature of EDCs is largely due to
      their bioaccumulation in the aquatic food chain our findings imply that the
      impact of these phytoplankton secretions needs to be investigated especially for
      seafoods, which are only a single trophic level away from phytoplankton.
      Alternatively, should these phytoplankton-origin EDCs not accumulate through
      marine food chains to significantly impact humans or marine mammals, our results
      indicate that functional assays could greatly over-estimate the risk from
      naturally occurring EDCs produced by marine phytoplankton. It remains to be
      determined if these EDCs affect zooplankton and other organisms that directly
      feed on marine phytoplankton, or if the secreted EDCs can directly impact other
      marine fauna.

PMID- 24927390
TI  - Genetic damage in coal miners evaluated by buccal micronucleus cytome assay.
AB  - During coal mining activities, large quantities of coal dust, ashes, polycyclic
      aromatic hydrocarbons and metals are released into the environment. This complex
      mixture presents one of the most important occupational hazards for health of
      workers. The aim of the present study was to evaluate the genetic damage together
      with the presence of inorganic elements, in an exposed workers population to coal
      mining residues of Guajira-Colombia. Thus, 100 exposed workers and 100 non
      exposed control individuals were included in this study. To determine genetic
      damage we assessed the micronucleus (MN) frequencies and nuclear buds in buccal
      mucosa samples (BMCyt) assay, which were significantly higher in the exposed
      group than non-exposed control group. In addition, karyorrhectic and karyolytic
      cells were also significantly higher in the exposed group (cell death). No
      significant difference was observed between the exposed groups engaged in
      different mining activities. No correlation between age, alcohol consumption,
      time of service and MN assay data were found in this study. However, the content
      of inorganic elements in blood samples analyzed by a Particle-induced X-ray
      emission technique (PIXE) showed higher values of silicon (Si) and aluminum (Al)
      in the exposed group. In this study we discuss the possibility of DNA damage
      observed in the mine workers cells be a consequence of oxidative damage.

PMID- 24927391
TI  - Multivariate geostatistical analyses of heavy metals in soils: spatial multi
      scale variations in Wulian, Eastern China.
AB  - The objective of this study was to examine spatial multi-scale variability of six
      heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) in relation to environmental factors in
      Wulian, Eastern China. Factorial kriging analysis (FKA) was applied to a data set
      consisting of 432 topsoils. We found that most of the heavy metal contents in
      soils did not exceed the guideline values of Environmental Quality Standard for
      Soils (EQSS) in China. Through linear model of coregionalization (LMC) fitting,
      spatial variation in six heavy metals could be grouped into one nugget effect,
      and two sphere structures with ranges of 6km (local scale) and 14km (regional
      scale). Spatial correlations among six heavy metals depended on local or regional
      scales. The high correlations between Cr, Ni and among Cd, Cu, Pb, Zn were found
      regardless of the spatial scale, while correlations of Cr and Ni with other four
      metals decreased with increasing spatial scale. Spatial variation of Cr and Ni
      was related to parent material at both local and regional scales, and was derived
      from natural sources. Mining activity was observed to affect the spatial
      variation of Cd, Cu, Pb and Zn at local scale, while parent material dominated
      spatial variation of those metals at regional scale. However, agricultural
      practices and human activity in urban area did not alter spatial variation of
      heavy metals in soils. It could be concluded that human influence on heavy metals
      variation was noted on local scale, and parent material had greater influence on
      spatial variation of heavy metals at both local and regional scales.

PMID- 24927392
TI  - Ecotoxicological impact of Zequanox(r), a novel biocide, on selected non-target
      Irish aquatic species.
AB  - Effective, species-specific zebra mussel control is needed urgently for Ireland's
      freshwater bodies, which became infested with non-native zebra mussels in the
      1990s. Zequanox(r), a newly commercialized product for zebra and quagga mussel
      control, is composed of dead Pseudomonas fluorescens CL 145A cells. This paper
      describes ecotoxicology tests on three representative native Irish freshwater
      species: Anodonta (duck mussel), Chironomus plumosus (non-biting midge), and
      Austropotamobius pallipes (white-clawed crayfish). The species were exposed to
      Zequanox in a 72-h static renewal toxicity test at concentrations of 100-750mg
      active ingredient per liter (mga.i./L). Water quality parameters were measured
      every 12-24h before and after water and product renewal. After 72h, endpoints
      were reported as LC10, LC50, and LC100. The LC50 values derived were (1)
      Anodonta: >=500mga.i./L (2) C. plumosus: 1075mga.i./L, and (3) A. pallipes:
      >=750mga.i./L. These results demonstrate that Zequanox does not negatively affect
      these organisms at the concentration required for >80percent zebra mussel
      mortality (150mg a.i/L) and the maximum allowable treatment concentration in the
      United Sates (200mga.i./L). They also show the overall species-specificity of
      Zequanox, and support its use in commercial facilities and open waters.

PMID- 24927393
TI  - The structure of 3-(diethylborylethynyl)pyridine: a nonplanarly arranged cyclic
      trimer.
AB  - 3-(Diethylborylethynyl)pyridines 2 assemble into a cyclic trimer stabilized via
      intermolecular boron-nitrogen coordination bonds both in solution and in the
      crystalline state. The outstanding structural features of the methoxy derivative
      2b in the crystalline state are that (1) two pyridine rings (P1 and P2) of the
      cyclic trimer of 2b are almost coplanar, and the third pyridine ring (P3) is
      largely bent away from P1 and P2, and (2) P3 of the cyclic trimer stacks in a
      face-to-face fashion with one of the pyridine rings (P3') of an adjacent cyclic
      trimer. The crystallographic study revealed that the conformation of the cyclic
      trimer is flexible enough to be affected by the crystal packing.

PMID- 24927394
TI  - Establishment of NOD/SCID mouse model of central nervous system leukemia.
AB  - In the present study, we successfully established a NOD/SCID mouse model of
      central nervous system leukemia by injection of acute monocytic leukemia cell
      line SHI-1 cells into the lateral ventricle. Immunohistochemistry was used to
      detect human leukocyte common antigen in brain slices. Nested PCR assay was used
      to detect MLL/AF6 fusion gene expression. After injection, the condition of the
      mice gradually progressed to cachexia and death (median survival time, 25 days).
      Leukemic cells were identified in the lung, bone marrow, and lymph node of one
      mouse. Brain tissue sections showed invasion into the subdural space, pia mater,
      arachnoid, along the Virchow-Robin space and into the deep brain parenchyma. In
      summary, a central nervous system leukemia (CNSL) model was established in
      NOD/SCID mice.

PMID- 24927395
TI  - A novel Affibody bioconjugate for dual-modality imaging of ovarian cancer.
AB  - An Affibody based dual imaging probe (PET and optical imaging) has been
      successfully developed. Dendrimer PAMAM G0 was used as a platform to assemble an
      NIRF dye, a metal chelator, and Affibody for dual modality imaging of ovarian
      cancer. Excellent tumor imaging quality was achieved in both modalities in the
      living tumor mice models. 

PMID- 24927396
TI  - Tryptophan and ATTO 590: mutual fluorescence quenching and exciplex formation.
AB  - Investigation of fluorescence quenching of probes, such as ATTO dyes, is becoming
      an increasingly important topic owing to the use of these dyes in super
      resolution microscopies and in single-molecule studies. Photoinduced electron
      transfer is their most important nonradiative pathway. Because of the increasing
      frequency of the use of ATTO and related dyes to investigate biological systems,
      studies are presented for inter- and intramolecular quenching of ATTO 590 with
      tryptophan. In order to examine intramolecular quenching, an ATTO 590-tryptophan
      conjugate was synthesized. It was determined that tryptophan is efficiently
      quenching ATTO 590 fluorescence by excited-state charge transfer and two charge
      transfer complexes are forming. In addition, it was discovered that an exciplex
      (whose lifetime is 5.6 ns) can be formed between tryptophan and ATTO 590, and it
      is suggested that the possibility of such exciplex formation should be taken into
      account when protein fluorescence is monitored in a system tagged with ATTO dyes.

PMID- 24927397
TI  - Strategies to enhance high pressure inactivation of murine norovirus in
      strawberry puree and on strawberries.
AB  - Due to the increasing concern of viral infection related to berries, this study
      investigated strategies to enhance high hydrostatic pressure (HHP) inactivation
      of murine norovirus 1 (MNV-1), a human norovirus (HuNoV) surrogate, on
      strawberries and in strawberry puree. Strawberry puree was inoculated with
      ~10(6)PFU/g of MNV-1 and treated at 350 MPa for 2 min at initial sample
      temperatures of 0, 5, 10 and 20 degrees C. MNV-1 became more sensitive to HHP as
      initial sample temperature decreased from 20 to 0 degrees C. To determine the
      effect of pressure cycling on MNV-1 inactivation, inoculated puree samples were
      treated at 300 MPa and 0 degrees C with 1, 2 and 4 cycles. Pressure cycling
      offered no distinct advantage over continuous HHP treatment. To determine the
      effect of presence of water during HHP on MNV-1 inactivation, strawberries
      inoculated with ~ 4 * 10(5)PFU/g of MNV-1 were either pressure-treated directly
      (dry state) or immersed in water during pressure treatment. MNV-1 was very
      resistant to pressure under the dry state condition, but became sensitive to
      pressure under the wet state condition. The inactivation curves of MNV-1 in
      strawberry puree and on strawberries were obtained at 300 and 350 MPa and initial
      sample temperature of 0 degrees C. Except for the curve of strawberries treated
      at 350 MPa which had a concave downward shape, the other three curves were almost
      linear with R(2) value of 0.99. The fate of MNV-1 in the un-treated and pressure
      treated strawberries and strawberry puree during frozen storage was determined.
      The virus was relatively stable and only reduced by <1.2 log during the 28-day
      frozen storage. In all, this study provides practical insights of designing
      strategies using HHP to inactivate HuNoV on strawberries and in strawberry puree
      assuming that HuNoV behaved similarly to MNV-1 when treated by HHP.

PMID- 24927398
TI  - Monitoring psychrotrophic lactic acid bacteria contamination in a ready-to-eat
      vegetable salad production environment.
AB  - A study monitoring lactic acid bacteria contamination was conducted in a company
      producing fresh, minimally processed, packaged and ready-to-eat (RTE) vegetable
      salads (stored at 4 degrees C) in order to investigate the reason for high
      psychrotrophic LAB levels in the products at the end of shelf-life. Initially,
      high microbial counts exceeding the established psychrotrophic thresholds (>10(7)
      10(8)CFU/g) and spoilage manifestations before the end of the shelf-life (7days)
      occurred in products containing an assortment of sliced and diced vegetables, but
      within a one year period these spoilage defects became prevalent in the entire
      processing plant. Environmental sampling and microbiological analyses of the raw
      materials and final products throughout the manufacturing process highlighted the
      presence of high numbers of Leuconostoc spp. in halved and unseeded, fresh sweet
      bell peppers provided by the supplier. A combination of two DNA fingerprinting
      techniques facilitated the assessment of the species diversity of LAB present in
      the processing environment along with the critical point of their introduction in
      the production facility. Probably through air mediation and surface adhesion,
      mainly members of the strictly psychrotrophic species Leuconostoc gelidum subsp.
      gasicomitatum and L. gelidum subsp. gelidum were responsible for the cross
      contamination of every vegetable handled within the plant. 

PMID- 24927399
TI  - High-throughput detection of food-borne pathogenic bacteria using oligonucleotide
      microarray with quantum dots as fluorescent labels.
AB  - Bacterial pathogens are mostly responsible for food-borne diseases, and there is
      still substantial room for improvement in the effective detection of these
      organisms. In the present study, we explored a new method to detect target
      pathogens easily and rapidly with high sensitivity and specificity. This method
      uses an oligonucleotide microarray combined with quantum dots as fluorescent
      labels. Oligonucleotide probes targeting the 16SrRNA gene were synthesized to
      create an oligonucleotide microarray. The PCR products labeled with biotin were
      subsequently hybridized using an oligonucleotide microarray. Following incubation
      with CdSe/ZnS quantum dots coated with streptavidin, fluorescent signals were
      detected with a PerkinElmer Gx Microarray Scanner. The results clearly showed
      specific hybridization profiles corresponding to the bacterial species assessed.
      Two hundred and sixteen strains of food-borne bacterial pathogens, including
      standard strains and isolated strains from food samples, were used to test the
      specificity, stability, and sensitivity of the microarray system. We found that
      the oligonucleotide microarray combined with quantum dots used as fluorescent
      labels can successfully discriminate the bacterial organisms at the genera or
      species level, with high specificity and stability as well as a sensitivity of 10
      colony forming units (CFU)/mL of pure culture. We further tested 105 mock
      contaminated food samples and achieved consistent results as those obtained from
      traditional biochemical methods. Together, these results indicate that the
      quantum dot-based oligonucleotide microarray has the potential to be a powerful
      tool in the detection and identification of pathogenic bacteria in foods. 

PMID- 24927400
TI  - Reciprocal regulation of adipocyte and osteoblast differentiation of mesenchymal
      stem cells by Eupatorium japonicum prevents bone loss and adiposity increase in
      osteoporotic rats.
AB  - Pathological increases in adipogenic potential with decreases in osteogenic
      differentiation occur in osteoporotic bone marrow cells. Previous studies have
      shown that bioactive materials isolated from natural products can reciprocally
      regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we
      showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid
      accumulation and inhibited the expression of adipocyte markers in multipotent
      C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline
      phosphatase activity and induced the expression of osteoblast markers in
      C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of
      EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone
      mineral density decrease. Finally, activity-guided fractionation led to the
      identification of coumaric acid and coumaric acid methyl ester as bioactive anti
      adipogenic and pro-osteogenic components in EJE. Taken together, our data
      indicate a promising possibility of E. japonicum as a functional food and as a
      therapeutic intervention for preventing osteoporosis and bone fractures.

PMID- 24927401
TI  - Cycle to cycle variability in a repetitive upper extremity task.
AB  - The purpose of this study was to examine the variability in muscle activity at
      rest and work during a repetitive task. A total of 20 participants performed a
      bimanual push task using three frequencies (4, 8, 16 pushes/min), three loads (1
      kg, 2 kg, 4 kg) and two grip conditions (no grip, 30% maximum). The coefficient
      of variation (CoV) of muscle activity was determined for the anterior deltoid,
      biceps brachii, extensor digitorum and flexor digitorum superficialis. Faster
      push frequencies and heavier loads had lower work-rest ratio CoV and higher mean
      muscle activity (p < 0.01). Sixteen pushes per minute produced the lowest CoV for
      the anterior deltoid (p < 0.01), while the 1- kg load produced the lowest CoV for
      the extensor digitorum and flexor digitorum superficialis (p < 0.01). Changes
      were driven by the rest phase rather than by the work phase, except for grip
      decreasing forearm muscle CoV. These findings underscore the importance of
      variability at rest and indicate that low variability of muscle activity is
      associated with ergonomic risk factors. PRACTITIONER SUMMARY: Decreased motor
      variability has been associated with pain and injury. A cyclical push task,
      evaluated in terms of work and rest phases, found that greater workloads
      increased variability primarily due to changes in the rest phase. Muscle
      variability, especially for the rest phase, may provide insight into injury risk.

PMID- 24927403
TI  - Detection of whitening agents in illegal cosmetics using attenuated total
      reflectance-infrared spectroscopy.
AB  - Cosmetic products containing illegal whitening agents are still found on the
      European market. They represent a considerable risk to public health, since they
      are often characterised by severe side effects when used chronically. The
      detection of such products at customs is not always simple, due to misleading
      packaging and the existence of products containing only legal components.
      Therefore there is a need for easy to use equipment and techniques to perform an
      initial screening of samples. The use of attenuated total reflectance-infrared
      (ATR-IR) spectroscopy, combined with chemometrics, was evaluated for that
      purpose. It was found that the combination of ATR-IR with the simple chemometric
      technique k-nearest neighbours gave good results. A model was obtained in which a
      minimum of illegal samples was categorised as legal. The correctly classified
      illegal samples could be attributed to the illegal components present. 

PMID- 24927402
TI  - Quantification of OSU-2S, a novel derivative of FTY720, in mouse plasma by liquid
      chromatography-tandem mass spectrometry.
AB  - OSU-2S is a novel anti-cancer and immune modulatory agent designed specifically
      to avert the immunosuppressive effects and related toxicities observed in
      clinical studies with its predecessor analog, FTY720. To characterize its
      preclinical pharmacokinetics, a liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method was developed and validated for the quantification of OSU-2S in
      mouse plasma. Ethyl acetate extraction of samples containing OSU-2S and the
      internal standard, Sph-17, was followed by separation with a 6min gradient
      (water/0.1% formic acid and methanol/0.1% formic acid) on a reverse-phase C18
      column at room temperature. Selected reaction monitoring was used for detection
      on a triple quadrupole mass spectrometer with positive ionization. The assay was
      linear over the concentration range 3-3000ng/mL with accuracy ranging from 103 to
      111%, and both within- and between-run precision (CV%) <=11%. All stability
      samples were within +/-15% of nominal values, and replicates were within 15% CV.
      The assay was successfully applied to a mouse pharmacokinetic study of OSU-2S
      with intravenous and intraperitoneal administration. OSU-2S non-compartmental
      pharmacokinetic parameters, area under the concentration-time curve, clearance,
      and elimination half-life were estimated at 1522hMUg/L, 3.06L/h/kg and 15.6h,
      respectively, for intravenous injection. Systemic availability after
      intraperitoneal injection was approximately 46%. These data demonstrate the OSU
      2S compound displays acceptable pharmacokinetic properties for further in vivo
      pharmacologic evaluation, which can be facilitated by the validated LC-MS/MS
      assay. 

PMID- 24927404
TI  - Modulatory effect of nano TiO2on Pb in Hoplias malabaricus trophically exposed.
AB  - This study investigated the hepatic and neural effects of TiO2 nanoparticle and
      Pb in Hoplias malabaricus trophically exposed. The alanine transaminase activity
      was altered at the high dose of exposed group to Pb and at the lowest doses of co
      exposed groups. It may reflect the hepatic effects of TiO2 on Pb toxicity, but
      the aspatate transaminase activity was not altered. The decreased injury index
      observed at the highest dose of co-exposed group compared to TiO2 may be related
      to the increased energy demand and can explain the more pronounced toxic effects
      observed in this group. The liver authomethallography revealed the metals
      presence at high dose groups. Serotonin concentration increased at the Pb lowest
      dose and at the highest dose of co-exposed group compare to control. Most
      importantly, when associated the contaminants were able to interact and altered
      some biomarkers. However, further studies, about action mechanisms of this co
      exposure are needed.

PMID- 24927405
TI  - Neurobehavioral and cytotoxic effects of vanadium during oligodendrocyte
      maturation: a protective role for erythropoietin.
AB  - Vanadium exposure has been known to lead to lipid peroxidation, demyelination and
      oligodendrocytes depletion. We investigated behaviour and glial reactions in
      juvenile mice after early neonatal exposure to vanadium, and examined the direct
      effects of vanadium in oligodendrocyte progenitor cultures from embryonic mice.
      Neonatal pups exposed to vanadium via lactation for 15 and 22 days all had lower
      body weights. Behavioural tests showed in most instances a reduction in locomotor
      activity and negative geotaxis. Brain analyses revealed astrocytic activation and
      demyelination in the vanadium exposed groups compared to the controls. In cell
      culture, exposure of oligodendrocytes to 300 MUM sodium metavanadate
      significantly increased cell death. Expression of the oligodendrocyte specific
      proteins, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and
      oligodendrocyte specific protein (OSP/Claudin) were reduced upon vanadium
      treatment while simultaneous administration of erythropoietin (EPO; 4-12 U/ml)
      counteracted vanadium-toxicity. The data suggest that oligodendrocyte damage may
      explain the increased vulnerability of the juvenile brain to vanadium and support
      a potential for erythropoietin as a protective agent against vanadium-toxicity
      during perinatal brain development and maturation.

PMID- 24927406
TI  - Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM
      model.
AB  - Despite evidence that deregulated Notch signalling is a master regulator of
      multiple myeloma (MM) pathogenesis, its contribution to myeloma bone disease
      remains to be resolved. Notch promotes survival of human MM cells and triggers
      human osteoclast activity in vitro. Here, we show that inhibition of Notch
      through the gamma-secretase inhibitor XII (GSI XII) induces apoptosis of murine
      MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine
      osteoclast differentiation of receptor activator of NF-kappaB ligand (RANKL)
      stimulated RAW264.7 cells in vitro. In the murine MOPC315.BM myeloma model GSI
      XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by
      diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and
      quantitative assessment of bone structure changes via high-resolution
      microcomputed tomography scans. Thus, we suggest that Notch inhibition through
      GSI XII controls myeloma bone disease mainly by targeting Notch in MM cells and
      possibly in osteoclasts in their microenvironment. We conclude that Notch
      inhibition is a valid therapeutic strategy in MM. 

PMID- 24927407
TI  - Distribution and levels of cell surface expression of CD33 and CD123 in acute
      myeloid leukemia.
AB  - Owing to the more recent positive results with the anti-CD33 immunotoxin
      gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting
      CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was
      studied by flow cytometry in a cohort of 319 patients with detailed information
      on French-American-British/World Health Organization (FAB/WHO) classification,
      cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would
      therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs
      express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be
      either targeted via CD33 or CD123. Simultaneous presence of both antigens was
      observed in 69.5% of patients. Most importantly, even AMLs with adverse
      cytogenetics express CD33 and CD123 levels comparable to those with favorable and
      intermediate subtypes. Some patient groups with unfavorable alterations, such as
      FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations,
      high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by
      high expression of CD33 and CD123. In addition, blasts of patients with mutant
      nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression
      pointing toward the possibility of minimal residual disease-guided interventions
      in mutated NPM1-positive AMLs. These results stimulate the development of novel
      concepts to redirect immune effector cells toward CD33- and CD123-expressing
      blasts using bi-specific antibodies or engineered T cells expressing chimeric
      antigen receptors. 

PMID- 24927409
TI  - Effects of chronic exposure to Aspergillus fumigatus on epidermal growth factor
      receptor expression in the airway epithelial cells of asthmatic rats.
AB  - Epidemiologic studies suggest that increased concentrations of airborne spores of
      Aspergillus fumigatus closely relate to asthma aggravation. Chronic exposure to
      A. fumigatus aggravates airway inflammation, remodeling, and airway
      hyperresponsiveness in asthmatic rats. The effects of chronic exposure to A.
      fumigatus on epidermal growth factor receptor (EGFR) expression in the airway
      epithelial cells of asthmatic rats remain unclear. This study aimed to
      investigate the effects of chronic exposure to A. fumigatus on injury and
      shedding of airway epithelium, goblet cell metaplasia, and EGFR expression in the
      airway epithelial cells of asthmatic rats. A rat model of chronic asthma was
      established using ovalbumin (OVA) sensitization and challenge. Rats with chronic
      asthma were then exposed to long-term inhalation of spores of A. fumigatus, and
      the dynamic changes in injury and shedding of airway epithelium, goblet cell
      metaplasia, and EGFR expression were observed and analyzed. Chronic exposure to
      A. fumigatus could aggravate airway epithelial cell damage, upregulate the
      expression of EGFR and its ligands EGF and TGF-alpha, promote goblet cell
      metaplasia, and increase airway responsiveness in rats with asthma. Chronic
      exposure to A. fumigatus upregulates the expression of EGFR and its ligands in
      asthmatic rats. The EGFR pathway may play a role in asthma aggravation induced by
      exposure to A. fumigatus.

PMID- 24927408
TI  - The novel immunotoxin HM1.24-ETA' induces apoptosis in multiple myeloma cells.
AB  - Despite new treatment modalities, the clinical outcome in a substantial number of
      patients with multiple myeloma (MM) has yet to be improved. Antibody-based
      targeted therapies for myeloma patients could make use of the HM1.24 antigen
      (CD317), a surface molecule overexpressed on malignant plasma cells and
      efficiently internalized. Here, a novel immunotoxin, HM1.24-ETA', is described.
      HM1.24-ETA' was generated by genetic fusion of a CD317-specific single-chain Fv
      (scFv) antibody and a truncated variant of Pseudomonas aeruginosa exotoxin A
      (ETA'). HM1.24-ETA' inhibited growth of interleukin 6 (IL-6)-dependent and 
      independent myeloma cell lines. Half-maximal growth inhibition was observed at
      concentrations as low as 0.3 nM. Target cell killing occurred via induction of
      apoptosis and was unaffected in co-culture experiments with bone marrow stromal
      cells. HM1.24-ETA' efficiently triggered apoptosis of freshly
      isolated/cryopreserved cells of patients with plasma cell leukemia and MM and was
      active in a preclinical severe combined immunodeficiency (SCID) mouse xenograft
      model. Importantly, HM1.24-ETA' was not cytotoxic against CD317-positive cells
      from healthy tissue (monocytes, human umbilical vein endothelial cells). These
      results indicate that CD317 may represent a promising target structure for
      specific and efficient immunotoxin therapy for patients with plasma cell tumors. 

PMID- 24927410
TI  - A HRM real-time PCR assay for rapid and specific identification of the emerging
      pest spotted-wing drosophila (Drosophila suzukii).
AB  - Spotted wing drosophila (Drosophila suzukii) is an emerging pest that began
      spreading in 2008 and its distribution now includes 13 countries across two
      continents. Countries where it is established have reported significant economic
      losses of fresh produce, such as cherries due to this species of fly. At larval
      stages, it is impossible to identify due to its striking similarities with other
      cosmopolitan and harmless drosophilids. Molecular methods allow identification
      but the current technique of DNA barcoding is time consuming. We developed and
      validated a rapid, highly sensitive and specific assay based on real-time PCR and
      high resolution melt (HRM) analysis using EvaGreen DNA intercalating dye
      chemistry. Performance characteristics of this qualitative assay, validation and
      applicability in a New Zealand quarantine framework are discussed. Application of
      this robust and independently validated assay across the spectrum of key food
      production and border protection industries will allow us to reduce the further
      spread of this damaging species worldwide. 

PMID- 24927411
TI  - Novel telomere-anchored PCR approach for studying sexual stage telomeres in
      Aspergillus nidulans.
AB  - Telomere length varies between germline and somatic cells of the same organism,
      leading to the hypothesis that telomeres are lengthened during meiosis. However,
      little is known about the meiotic telomere length in many organisms. In the
      filamentous fungus Aspergillus nidulans, the telomere lengths in hyphae and
      asexual spores are invariant. No study using existing techniques has determined
      the telomere length of the sexual ascospores due to the relatively low abundance
      of pure meiotic cells in A. nidulans and the small quantity of DNA present. To
      address this, we developed a simple and sensitive PCR strategy to measure the
      telomere length of A. nidulans meiotic cells. This novel technique, termed
      "telomere-anchored PCR," measures the length of the telomere on chromosome II-L
      using a small fraction of the DNA required for the traditional terminal
      restriction fragment (TRF) Southern analysis. Using this approach, we determined
      that the A. nidulans ascospore telomere length is virtually identical to
      telomeres of other cell types from this organism, approximately 110 bp,
      indicating that a surprisingly strict telomere length regulation exists in the
      major cell types of A. nidulans. When the hyphal telomeres were measured in a
      telomerase reverse transcriptase (TERT) knockout strain, small decreases in
      length were readily detected. Thus, this technique can detect telomeres in
      relatively rare cell types and is particularly sensitive in measuring
      exceptionally short telomeres. This rapid and inexpensive telomere-anchored PCR
      method potentially can be utilized in other filamentous fungi and types of
      organisms. 

PMID- 24927412
TI  - Evaluation of reference genes for quantitative real-time PCR in oil palm elite
      planting materials propagated by tissue culture.
AB  - BACKGROUND: The somatic embryogenesis tissue culture process has been utilized to
      propagate high yielding oil palm. Due to the low callogenesis and embryogenesis
      rates, molecular studies were initiated to identify genes regulating the process,
      and their expression levels are usually quantified using reverse transcription
      quantitative real-time PCR (RT-qPCR). With the recent release of oil palm genome
      sequences, it is crucial to establish a proper strategy for gene analysis using
      RT-qPCR. Selection of the most suitable reference genes should be performed for
      accurate quantification of gene expression levels. RESULTS: In this study, eight
      candidate reference genes selected from cDNA microarray study and literature
      review were evaluated comprehensively across 26 tissue culture samples using RT
      qPCR. These samples were collected from two tissue culture lines and media
      treatments, which consisted of leaf explants cultures, callus and embryoids from
      consecutive developmental stages. Three statistical algorithms (geNorm,
      NormFinder and BestKeeper) confirmed that the expression stability of novel
      reference genes (pOP-EA01332, PD00380 and PD00569) outperformed classical
      housekeeping genes (GAPDH, NAD5, TUBULIN, UBIQUITIN and ACTIN). PD00380 and
      PD00569 were identified as the most stably expressed genes in total samples, MA2
      and MA8 tissue culture lines. Their applicability to validate the expression
      profiles of a putative ethylene-responsive transcription factor 3-like gene
      demonstrated the importance of using the geometric mean of two genes for
      normalization. CONCLUSIONS: Systematic selection of the most stably expressed
      reference genes for RT-qPCR was established in oil palm tissue culture samples.
      PD00380 and PD00569 were selected for accurate and reliable normalization of gene
      expression data from RT-qPCR. These data will be valuable to the research
      associated with the tissue culture process. Also, the method described here will
      facilitate the selection of appropriate reference genes in other oil palm tissues
      and in the expression profiling of genes relating to yield, biotic and abiotic
      stresses.

PMID- 24927414
TI  - Diversity of killer cell immunoglobulin-like receptor (KIR) genotypes and
      KIR2DL2/3 variants in HCV treatment outcome.
AB  - The aim of this study was to analyse the distribution of KIR haplotypes and the
      KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the
      influence on the response to pegylated interferon plus ribavirin classical
      treatment. The alleles study of previously associated KIR2DL2/3 showed that
      KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and
      KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%,
      p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs.
      45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned
      on the basis of previous studies. The centromeric A/A genotype was more frequent
      in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to
      be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic
      regression model showed the importance of KIR genes in predicting the response to
      combined treatment, since the positive predictive value (PPV) was improved (from
      55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3
      rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for
      predicting the combined treatment response in patients with chronic HCV infection
      in association with the determination of IFNL3 polymorphism. 

PMID- 24927415
TI  - The expression of the hepatocyte SLAMF3 (CD229) receptor enhances the hepatitis C
      virus infection.
AB  - Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer
      worldwide. We recently characterized for the first time the expression of
      Signaling Lymphocyte Activating Molecule 3 (SLAMF3) in human hepatocytes and
      here, we report that SLAMF3 interacts with the HCV viral protein E2 and is
      implicated in HCV entry process. We found a strong correlation between SLAMF3
      expression level and hepatocyte susceptibility to HCV infection. The use of
      specific siRNAs to down-modulate SLAMF3 expression and SLAMF3-blocking antibodies
      both decreased the hepatocytes susceptibility to HCV infection. Moreover, SLAMF3
      over-expression significantly increased susceptibility to HCV infection.
      Interestingly, experiments with peptides derived from each SLAMF3 domain showed
      that the first N-terminal extracellular domain is essential for interaction with
      HCV particles. Finally, we showed that recombinant HCV envelop protein E2 can
      bind SLAMF3 and that anti-SLAMF3 antibodies inhibited specifically this
      interaction. Overall, our results revealed that SLAMF3 plays a role during HCV
      entry, likely by enhancing entry of viral particle within hepatocytes. 

PMID- 24927417
TI  - Quantitative analyses of CTP-499 and five major metabolites by core-structure
      analysis.
AB  - CTP-499 is a novel oral multi-subtype selective inhibitor of PDEs that is
      currently in clinical testing, in combination with angiotensin modulators, as a
      potentially first-in-class treatment for diabetic kidney disease. The compound
      was discovered and developed by using Concert's proprietary DCE Platform((r)) in
      which deuterium was incorporated at select positions of 1-((S)-5-hydroxyhexyl)
      3,7-dimethylxanthine (HDX). CTP-499 metabolizes to five major metabolites: C
      21256, D-M2, D-M3, D-M4 and M5, of which all contains deuterium except M5. During
      in vivo metabolism, however, H/D exchange takes place. As a result, each analyte,
      except M5, has multiple molecular masses. To accurately quantify the analytes, we
      developed an LC-MS/MS method focusing on the core structures of the molecules,
      termed "core-structure analyses". The core-structure analyses method was then
      validated under GLP guidance in dog, rat and rabbit plasma, with a sample volume
      of 50 MUL. Results demonstrated that this approach accurately quantifies each of
      the six analytes despite partial exchange of deuterium with hydrogen atoms in the
      in vivo samples. The validation parameters included accuracy, precision,
      sensitivity, stability, dilution integrity, hemolysis, matrix effect,
      selectivity, and recovery. Acceptable intra-run and inter-run assay precision
      (%CV <= 5.5%) and accuracy (90.1-106.7%) were achieved over a linear range of 10
      5,000 ng/mL of each analyte. Various stability tests, including bench-top,
      freeze/thaw, stock solution, and long-term storage, were also performed. All
      stability results met acceptance criteria. The robustness of the methods was
      demonstrated by the incurred sample reproducibility (ISR) tests. After
      validation, the method was successfully used in support of multiple toxicological
      studies of CTP-499.

PMID- 24927416
TI  - Incretin receptor null mice reveal key role of GLP-1 but not GIP in pancreatic
      beta cell adaptation to pregnancy.
AB  - Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional
      receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide
      (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in
      islet and beta cell area, numbers of medium/large sized islets, with positive
      effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic
      insulin content. Alpha cell area and glucagon content were unchanged but
      prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1
      and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet
      adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This
      was associated with abolition of normal pregnancy-induced increases in plasma
      GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate
      that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related
      adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1. 

PMID- 24927418
TI  - An improved method to extract and purify cystatin from hen egg white.
AB  - Hen egg white cystatin, an inhibitor of cysteine proteinase, may have wide
      applications for improving human health. However, its pricy cost associated with
      extraction and preparation has hurdled its further utilization. The objective was
      to develop an improved method to extract and purify cystatin from egg white.
      After removal of ovomucin, a fraction containing cystatin was obtained by cation
      exchange chromatography, and further purified by affinity chromatography using a
      cm-papain-Sepharose column. The prepared cystatin was then characterized by SDS
      PAGE, Western-Blot, and LC-MS/MS, and its purity was determined by HPLC method
      instead of the conventional immunodiffusion method. The protein content of
      cystatin extract was 66.4 +/- 2.3%. In comparison with the conventional method,
      the purity of cystatin was improved from 56.6 +/- 1.7% to 93.3 +/- 4.0%, and its
      yield was improved from 21.3 +/- 1.2% to 33.6 +/- 1.5%. Relative activities of
      cystatin to inhibit papain prepared by our method and the conventional method
      were determined to be 88 +/- 7% and 91 +/- 4% respectively, against a cystatin
      standard from Sigma. This suggested no significant loss of activity during the
      separation process.

PMID- 24927419
TI  - Simultaneous determination of bioactive components of Radix Angelicae Sinensis
      Radix Paeoniae Alba herb couple in rat plasma and tissues by UPLC-MS/MS and its
      application to pharmacokinetics and tissue distribution.
AB  - A highly sensitive and rapid ultra performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous
      quantification of seven components in rat plasma and five components in rat
      tissues after oral administration of the extracts of different combination Radix
      Angelicae Sinensis-Radix Paeoniae Alba herb couple and has been applied to
      compare the different pharmacokinetics and tissue distribution properties of
      these bioactive components. The extracts of Radix Angelicae Sinensis (RAS), Radix
      Paeoniae Alba (RPA) and Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple
      (RRHC) were orally administrated to rats, respectively. The concentrations of
      ferulic acid, caffeic acid, vanillic acid, ligustilide, paeoniflorin, albiflorin
      and oxypaeoniflorin in rat plasma and the concentrations of ferulic acid,
      vanillic acid, paeoniflorin, albiflorin and oxypaeoniflorin in tissues were
      determined by UPLC-MS/MS. The plasma samples were pretreated by protein
      precipitation with methanol and the tissue samples were homogenated with water
      and pretreated by protein precipitation with methanol. Chromatographic separation
      was performed on a C18 column using 0.1% formic acid-acetonitrile as mobile phase
      for gradient elution. A triple quadrupole (TQ) tandem mass spectrometry equipped
      with an electrospray ionization source was used as detector operating both in
      positive and negative ionization mode and operated by multiple-reaction
      monitoring (MRM) scanning. Noncompartmental pharmacokinetic parameters were
      calculated by DAS 2.0 program. The differences between each group were compared
      by SPSS 16.0 with Independent-Samples T-test. The pharmacokinetic parameters
      (such as Cmax, Tmax, T1/2, AUC0-T, MRT0-T, Vz/F or CLz/F) of all the detected
      components between the single herb (RAS or RPA) and herb pair (RRHP) showed
      significant differences (P<0.05). It indicated that the compatibility of RAS and
      RPA could alter the pharmacokinetics features of each component. Tissue
      distribution results showed that ferulic acid, vanillic acid, paeoniflorin,
      albiflorin and oxypaeoniflorin mostly distributed in liver and kidney both in
      herb couple and single herb distributed most in liver and kidney. Compared with
      single herb, RRHC could increase or decrease the concentrations of five
      components at different time points compared with the sing herb. The results
      indicated the method was successfully applied to the comparative study on
      pharmacokinetics and tissue distribution of different combination of RRHC in
      rats. The compatibility of two Chinese herbs could alter the pharmacokinetics and
      tissue distribution properties of major bio-active components in the single herb.
      The results might be helpful for further investigation of compatibility mechanism
      of RRHC.

PMID- 24927420
TI  - Sedimentation field flow fractionation monitoring of in vitro enrichment in
      cancer stem cells by specific serum-free culture medium.
AB  - The development of methods to enrich cell populations for cancer stem cells (CSC)
      is urgently needed to help understand tumor progression, therapeutic escape and
      to evaluate new drugs, in particular for colorectal cancer (CRC). In this work,
      we describe the in vitro use of OncoMiD for colon, a CRC-specific primary cell
      culture medium, to enrich CRC cell lines in CSC. Sedimentation field flow
      fractionation (SdFFF) was used to monitor the evolution of subpopulations
      composition. In these models, medium induced a loss of adherence properties
      associated with a balance between proliferation and apoptosis rates and, more
      important, an increased expression of relevant CSC markers, leading to specific
      SdFFF elution profile changes. 

PMID- 24927421
TI  - Attitudinal and behavioral characteristics predict high risk sexual activity in
      rural Tanzanian youth.
AB  - The incidence of HIV infection in rural African youth remains high despite
      widespread knowledge of the disease within the region and increasing funds
      allocated to programs aimed at its prevention and treatment. This suggests that
      program efficacy requires a more nuanced understanding of the profiles of the
      most at-risk individuals. To evaluate the explanatory power of novel
      psychographic variables in relation to high-risk sexual behaviors, we conducted a
      survey to assess the effects of psychographic factors, both behavioral and
      attitudinal, controlling for standard predictors in 546 youth (12-26 years of
      age) across 8 villages in northern Tanzania. Indicators of high-risk sexual
      behavior included HIV testing, sexual history (i.e., virgin/non-virgin), age of
      first sexual activity, condom use, and number of lifetime sexual partners.
      Predictors in the statistical models included standard demographic variables,
      patterns of media consumption, HIV awareness, and six new psychographic features
      identified via factor analyses: personal vanity, family-building values, ambition
      for higher education, town recreation, perceived parental strictness, and
      spending preferences. In a series of hierarchical regression analyses, we find
      that models including psychographic factors contribute significant additional
      explanatory information when compared to models including only demographic and
      other conventional predictors. We propose that the psychographic approach used
      here, in so far as it identifies individual characteristics, aspirations, aspects
      of personal life style and spending preferences, can be used to target
      appropriate communities of youth within villages for leading and receiving
      outreach, and to build communities of like-minded youth who support new patterns
      of sexual behavior. 

PMID- 24927422
TI  - Transcriptome profiling to discover putative genes associated with paraquat
      resistance in goosegrass (Eleusine indica L.).
AB  - BACKGROUND: Goosegrass (Eleusine indica L.), a serious annual weed in the world,
      has evolved resistance to several herbicides including paraquat, a non-selective
      herbicide. The mechanism of paraquat resistance in weeds is only partially
      understood. To further study the molecular mechanism underlying paraquat
      resistance in goosegrass, we performed transcriptome analysis of susceptible and
      resistant biotypes of goosegrass with or without paraquat treatment. RESULTS: The
      RNA-seq libraries generated 194,716,560 valid reads with an average length of
      91.29 bp. De novo assembly analysis produced 158,461 transcripts with an average
      length of 1153.74 bp and 100,742 unigenes with an average length of 712.79 bp.
      Among these, 25,926 unigenes were assigned to 65 GO terms that contained three
      main categories. A total of 13,809 unigenes with 1,208 enzyme commission numbers
      were assigned to 314 predicted KEGG metabolic pathways, and 12,719 unigenes were
      categorized into 25 KOG classifications. Furthermore, our results revealed that
      53 genes related to reactive oxygen species scavenging, 10 genes related to
      polyamines and 18 genes related to transport were differentially expressed in
      paraquat treatment experiments. The genes related to polyamines and transport are
      likely potential candidate genes that could be further investigated to confirm
      their roles in paraquat resistance of goosegrass. CONCLUSION: This is the first
      large-scale transcriptome sequencing of E. indica using the Illumina platform.
      Potential genes involved in paraquat resistance were identified from the
      assembled sequences. The transcriptome data may serve as a reference for further
      analysis of gene expression and functional genomics studies, and will facilitate
      the study of paraquat resistance at the molecular level in goosegrass.

PMID- 24927423
TI  - Future oceanic warming and acidification alter immune response and disease status
      in a commercial shellfish species, Mytilus edulis L.
AB  - Increases in atmospheric carbon dioxide are leading to physical changes in marine
      environments including parallel decreases in ocean pH and increases in seawater
      temperature. This study examined the impacts of a six month exposure to combined
      decreased pH and increased temperature on the immune response and disease status
      in the blue mussel, Mytilus edulis L. Results provide the first confirmation that
      exposure to future acidification and warming conditions via aquarium-based
      simulation may have parallel implications for bivalve health. Collectively, the
      data suggests that temperature more than pH may be the key driver affecting
      immune response in M. edulis. Data also suggests that both increases in
      temperature and/or lowered pH conditions may lead to changes in parasite
      abundance and diversity, pathological conditions, and bacterial incidence in M.
      edulis. These results have implications for future management of shellfish under
      a predicted climate change scenario and future sustainability of shellfisheries.
      Examination of the combined effects of two stressors over an extended exposure
      period provides key preliminary data and thus, this work represents a unique and
      vital contribution to current research efforts towards a collective understanding
      of expected near-future impacts of climate change on marine environments. 

PMID- 24927424
TI  - Preference for different anchor descriptors on visual analogue scales among
      Japanese patients with chronic pain.
AB  - CONTEXT: Although many previous studies have examined the preference of patients
      for different pain measurement scales, preference for anchor descriptors has not
      been thoroughly discussed. OBJECTIVES: To examine (1) the preferred end-phrases
      used in the VAS as anchor labels for Japanese patients with chronic pain, and (2)
      whether the preference differs according to factors such as age, sex, educational
      level, duration of pain, and pain intensity. METHODS: We performed an
      observational study in patients suffering from non-cancer chronic pain for more
      than 3 months at a pain center in Japan. The patients were asked to rate their
      pain intensity using four types of VAS that used the following different anchor
      descriptors: "worst pain" ("Worst"), "worst pain bearable" ("Bearable"), "worst
      pain imaginable" ("Imaginable"), and "worst pain you have ever experienced"
      ("Experienced"). They were also asked to rank the four scales according to ease
      of responding, and asked which descriptor best reflected their perceived pain.
      RESULTS: In total, 183 patients participated in the study. They consisted of 119
      (65.0%) women and 64 (35.0%) men aged 18-84 years with the mean age of 56.9
      years. "Experienced" was most preferred (69.8%), followed by "Bearable" (66.3%),
      "Worst" (48.8%), and "Imaginable" (16.9%). Factors such as age, sex, educational
      background, duration of pain, and pain intensity did not significantly affect the
      results. In 83.1% of patients, the preferred descriptor corresponded to the
      descriptor that best reflected patients' perceived pain. CONCLUSION: The
      frequently used expression "worst pain imaginable" is considered to be difficult
      to understand for most patients. Widely preferred descriptors, such as "worst
      pain you have ever experienced" and "worst pain bearable", should be used when
      evaluating perceived pain. The preference of anchor descriptors was not
      significantly affected by the factors such as age, sex, educational level,
      duration of pain, and pain intensity.

PMID- 24927426
TI  - MHC-matched induced pluripotent stem cells can attenuate cellular and humoral
      immune responses but are still susceptible to innate immunity in pigs.
AB  - Recent studies have revealed negligible immunogenicity of induced pluripotent
      stem (iPS) cells in syngeneic mice and in autologous monkeys. Therefore, human
      iPS cells would not elicit immune responses in the autologous setting. However,
      given that human leukocyte antigen (HLA)-matched allogeneic iPS cells would
      likely be used for medical applications, a more faithful model system is needed
      to reflect HLA-matched allogeneic settings. Here we examined whether iPS cells
      induce immune responses in the swine leukocyte antigen (SLA)-matched setting. iPS
      cells were generated from the SLA-defined C1 strain of Clawn miniature swine,
      which were confirmed to develop teratomas in mice, and transplanted into the
      testes (n = 4) and ovary (n = 1) of C1 pigs. No teratomas were found in pigs on
      47 to 125 days after transplantation. A Mixed lymphocyte reaction revealed that T
      cell responses to the transplanted MHC-matched (C1) iPS cells were significantly
      lower compared to allogeneic cells. The humoral immune responses were also
      attenuated in the C1-to-C1 setting. More importantly, even MHC-matched iPS cells
      were susceptible to innate immunity, NK cells and serum complement. iPS cells
      lacked the expression of SLA class I and sialic acids. The in vitro cytotoxic
      assay showed that C1 iPS cells were targeted by NK cells and serum complement of
      C1. In vivo, the C1 iPS cells developed larger teratomas in NK-deficient NOG (T-B
      NK-) mice (n = 10) than in NK-competent NOD/SCID (T-B-NK+) mice (n = 8) (p<0.01).
      In addition, C1 iPS cell failed to form teratomas after incubation with the
      porcine complement-active serum. Taken together, MHC-matched iPS cells can
      attenuate cellular and humoral immune responses, but still susceptible to innate
      immunity in pigs. 

PMID- 24927428
TI  - [Etiology of anti-N-methyl-D-aspartate receptor encephalitis].
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of newly
      recognized autoimmune encephalitis which is commonly seen in children, but its
      precise etiology is still uncertain. To reveal the etiology of anti-NMDAR
      encephalitis is very necessary for understanding its pathology, and for starting
      immune-related therapy as early as possible to improve its prognosis. In the
      initial literature, tumor, especially teratoma is more related with the anti
      NMDAR encephalitis. In recent research, its etiology is related to infection and
      heredity. This article reviews the recognition and variation of the etiology of
      anti-NMDAR encephalitis. 

PMID- 24927427
TI  - An active poroelastic model for mechanochemical patterns in protoplasmic droplets
      of Physarum polycephalum.
AB  - Motivated by recent experimental studies, we derive and analyze a two-dimensional
      model for the contraction patterns observed in protoplasmic droplets of Physarum
      polycephalum. The model couples a description of an active poroelastic two-phase
      medium with equations describing the spatiotemporal dynamics of the intracellular
      free calcium concentration. The poroelastic medium is assumed to consist of an
      active viscoelastic solid representing the cytoskeleton and a viscous fluid
      describing the cytosol. The equations for the poroelastic medium are obtained
      from continuum force balance and include the relevant mechanical fields and an
      incompressibility condition for the two-phase medium. The reaction-diffusion
      equations for the calcium dynamics in the protoplasm of Physarum are extended by
      advective transport due to the flow of the cytosol generated by mechanical
      stress. Moreover, we assume that the active tension in the solid cytoskeleton is
      regulated by the calcium concentration in the fluid phase at the same location,
      which introduces a mechanochemical coupling. A linear stability analysis of the
      homogeneous state without deformation and cytosolic flows exhibits an oscillatory
      Turing instability for a large enough mechanochemical coupling strength.
      Numerical simulations of the model equations reproduce a large variety of wave
      patterns, including traveling and standing waves, turbulent patterns, rotating
      spirals and antiphase oscillations in line with experimental observations of
      contraction patterns in the protoplasmic droplets. 

PMID- 24927429
TI  - [Research advances in pathogenesis of anti-N-methyl-D-aspartate receptor
      encephalitis].
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most prevalent
      type of encephalitis. Investigating the pathogenesis of anti-NMDAR encephalitis
      will enhance our understanding of this disease and play a central part in
      providing reasonable treatment for the patients. The pathogenesis is elucidated
      as follows: (1) the findings of the relationship between anti-NMDAR encephalitis
      and tumors; (2) further research on the relationship between anti-NMDAR
      encephalitis and tumors; (3) NMDAR epitopes and the autoimmunity of patients; (4)
      the interaction between antibody and NMDAR; (5) the pathogenesis of anti-NMDAR
      encephalitis without tumors. This review gives a brief introduction to the
      methodology and way of finding out the valuable clinical problems and making a
      clear and explicit explanation of them by exhibiting the process of discovering
      the disease, disclosing its relationship with tumors, and investigating its
      pathological and molecular mechanism. Current studies have demonstrated that anti
      NMDAR encephalitis is an autoimmune disease of the nervous system that is closely
      associated with tumors, particularly ovarian teratoma. 

PMID- 24927430
TI  - [Clinical presentations of pediatric anti-N-methyl-D-aspartate receptor
      encephalitis].
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common
      autoimmune encephalitis in children with characterized clinical features. Here we
      review clinical presentations of typical and atypical anti-NMDAR encephalitis and
      characteristics of clinical presentations of pediatric anti-NMDAR encephalitis. 

PMID- 24927431
TI  - [Diagnosis and differential diagnosis of anti-N-methyl-D-aspartate receptor
      encephalitis in children].
AB  - Autoimmune encephalitis is rare and has various clinical manifestations, which
      may hamper the correct diagnosis. Therefore, the pediatrician should be familiar
      with the clinical symptoms, signs, laboratory features, neuroimaging changes,
      immunological characteristics, and differential diagnosis of this disease. In
      order to correctly diagnose anti-N-methyl-D-aspartate receptor (NMDAR)
      encephalitis, cerebrospinal fluid (CSF) examinations including detection of
      oligoclonal bands, brain MRI scanning, and routine EEG and/or 24 hours video EEG
      should be performed in children. For highly suspected cases, particularly
      children presenting with psychiatric symptoms and epileptic seizures,
      examinations should be done to detect anti-NMDAR antibodies (Abs) in serum and
      CSF. A notable feature in children is the EEG pattern named "extreme delta
      brush", which may help confirm the clinical diagnosis. Anti-NMDAR Abs in CSF is
      the diagnostic "gold-standard" for this disease. The differential diagnosis of
      anti-NMDAR encephalitis is broad. In pediatric patients, the differential
      diagnosis should be made mainly with herpes simplex virus encephalitis, other
      autoimmune encephalitis, and psychosis. 

PMID- 24927432
TI  - [Management of anti-N-methyl-D-aspartate receptor encephalitis in children].
AB  - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a new category of
      severe, potentially treatable autoimmune encephalitis and can appear in patients
      of all ages, but more frequently in children. It is a highly characteristic
      syndrome evolving in five stages: the prodromal phase (viral infection-like
      symptoms), psychotic phase, unresponsive phase, hyperkinetic phase, and gradual
      recovery phase. The treatment for this disorder includes first-line immunotherapy
      (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy
      (rituximab, cyclophosphamide), and tumor removal. Hereby the progresses,
      selections and shortcomings of the treatment protocols for this disease are
      introduced. 

PMID- 24927433
TI  - [Types of acute hypoxic-ischemic brain injury due to perinatal sentinel events in
      neonates].
AB  - OBJECTIVE: To investigate the clinical and imaging characteristics of acute
      hypoxic-ischemic brain injury (HIBI) due to perinatal sentinel events in
      neonates. METHODS: Forty-six neonates with acute HIBI who were admitted between
      January 2004 and May 2013, and who had a history of major cardiopulmonary
      resuscitation, were enrolled in the study. They were classified into full-term
      and preterm infants to analyze the clinical and imaging characteristics. RESULTS:
      Among full-term infants, the incidence rates of white matter injury, cortical
      injury, basal ganglia /thalamic injury, and brain stem injury were 95%, 90%, 75%,
      and 65%, respectively; among preterm infants, the incidence rates of white matter
      injury, cortical injury, basal ganglia/thalamic injury, and brain stem injury
      were 73%, 23%, 19%, and 15%, respectively. Compared with full-term infants,
      preterm infants had a significantly lower incidence of gray matter injury in the
      cortex, basal ganglia/thalamus, and brain stem (P<0.05). About 46% of all
      subjects had multiple organ dysfunction. The 20 full-term infants with HIBI had
      typical clinical manifestations; 19 (95%) of them had moderate or severe neonatal
      encephalopathy, with mixed lesions on magnetic resonance imaging (MRI), and
      moderate or severe basal ganglia/thalamic injury was found in 68% of these
      patients. Multiple organ dysfunction, various abnormal neurological
      manifestations, and arterial blood pH less than 7.1 were closely related to
      moderate or severe brain injury. CONCLUSIONS: White matter injury is the most
      common type of HIBI. Gray matter injury can be found in preterm infants, but the
      incidence is lower than that in full-term infants. Moderate or severe neonatal
      encephalopathy is mainly manifested as basal ganglia/thalamic injury on MRI.
      Evaluation of multiple organ dysfunction and abnormal neurological manifestations
      and early blood gas analysis are very important for the diagnosis of neonatal
      HIBI.

PMID- 24927434
TI  - [Analysis of survival and prognostic factors in extremely preterm infants].
AB  - OBJECTIVE: To investigate the survival rate, complications during
      hospitalization, and prognostic factors in extremely preterm infants (gestational
      age less than 28 weeks) in the neonatal intensive care unit (NICU). METHODS: A
      retrospective analysis was performed on 90 extremely preterm infants who were
      admitted to the NICU between January 2011 and March 2013 to investigate the
      perinatal data, delivery and resuscitation, ventilation/oxygen supply during
      hospitalization, mortality, and the incidence of severe (grade III/IV)
      intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy
      of prematurity (ROP), patent ductus arteriosus (PDA), and septicemia. RESULTS:
      Among the 90 extremely preterm infants, the gestational age, birth weight,
      overall survival rate, mortality, and withdrawal rate were 26+/-1 weeks, 898+/
      165 g, 57%, 9%, and 34%, respectively. The incidence rates of neonatal
      respiratory distress syndrome, BPD, PDA, ROP, and grade III/IV IVH were 88%, 85%,
      69%, 68%, and 31%, respectively. The surviving infants had a mean length of
      hospital stay of 83+/-18 days and a mean weight at discharge of 2 419+/-300 g.
      The multivariate logistic regression analysis showed that grade III/IV IVH and
      pulmonary hemorrhage were high-risk factors for death or withdrawal, while
      antenatal corticosteroids were the protective factor for outcome (P<0.05).
      CONCLUSIONS: The survival rate of extremely preterm infants is still much lower
      than that in developed countries. grade III/IV IVH, and pulmonary hemorrhage are
      important prognostic factors.

PMID- 24927435
TI  - [Prognostic factors in very low birth weight infants and extremely low birth
      weight infants].
AB  - OBJECTIVE: To analyze the clinical data of very low birth weight infants (VLBWIs)
      and extremely low birth weight infants (ELBWIs) (birth weight <=1 200 g) and to
      provide prewarning indicators for prognostic evaluation and clinical
      intervention. METHODS: A retrospective analysis was performed on the clinical
      data of 108 VLBWIs and ELBWIs to investigate the maternal history of diseases
      during pregnancy, neonatal birth status, the process of diagnosis and treatment,
      and prognosis. Unconditional logistic regression analysis was used to determine
      prognostic factors. RESULTS: Of the 108 preterm infants, 15 had a birth weight of
      <800 g, 29 had a birth weight of 800-999 g, and 64 had a birth weight of 1000
      1200 g. The mortality was 33.3% (36/108). Placenta previa and Apgar score <=3 at
      5 minutes were the main risk factors for death within 24 hours of birth;
      premature rupture of membrane, Apgar score <=3 at 5 minutes, and pulmonary
      hemorrhage were the main risk factors for death between 24 hours and 7 days after
      birth; late-onset sepsis caused by invasive fungal infection was an independent
      risk factor for death over 7 days after birth, while pregnancy-induced
      hypertension syndrome was a protective factor. CONCLUSIONS: The mortality in
      VLBWIs and ELBWIs is relatively high, and the prognostic factors vary between
      preterm infants of different ages. Clinicians should discuss management options
      for the infants on the basis of these findings to increase the survival of
      preterm infants.

PMID- 24927436
TI  - [Effect of oral administration of probiotics on intestinal colonization with drug
      resistant bacteria in preterm infants].
AB  - OBJECTIVE: To evaluate the effect of oral administration of probiotics on
      intestinal colonization with drug-resistant bacteria among preterm infants in the
      neonatal intensive care unit (NICU). METHODS: A double-blind, randomized, placebo
      controlled trial was carried out in the preterm infants who were transferred to
      the NICU immediately after birth. These infants were stratified by whether they
      were breastfed and then randomized into test group and control group. The test
      group was given probiotics from the day when enteral feeding began, while the
      control group was treated conventionally without probiotics. The two groups were
      compared in terms of the colonization with extended-spectrum beta-lactamase
      producing bacteria, as assessed by rectal swabs on days 1, 3, 7, and 14 after
      birth, and the incidence of diseases. RESULTS: Rectal colonization with drug
      resistant bacteria was found in the test group (n=119) and control group (n=138)
      on days 1, 3, 7, and 14 after birth. There were no significant differences in the
      incidence of late-onset sepsis and necrotizing enterocolitis between the two
      groups (P>0.05). Among non-breastfed infants, the test group had significantly
      decreased rectal colonization with drug-resistant bacteria compared with the
      control group on day 14 after birth (71.1% vs 88.9%; P=0.04). No probiotic
      related adverse events were observed in the study. CONCLUSIONS: Oral
      administration of probiotics may reduce rectal colonization with drug-resistant
      bacteria in preterm infants under certain conditions and shows good safety.

PMID- 24927437
TI  - [Risk factors for the failure of the InSure method in very preterm infants with
      respiratory distress syndrome].
AB  - OBJECTIVE: To study the risk factors for the failure of the InSure method in very
      preterm infants with respiratory distress syndrome (RDS). METHODS: Seventy-one
      very preterm infants with RDS treated with InSure method were enrolled. These
      infants were categorized into two groups: InSure success (42 cases) and InSure
      failure (29 cases). The differences in basic information were compared between
      the two groups, and logistic regression analysis was used to identify the risk
      factors for InSure failure. RESULTS: The failure rate of the InSure method was
      41%. The failure group were much lower in the birth weight, the antenatal
      steroids utilization rate and the vaginal delivery rate than the success group
      (P<0.05). The incidence of patent ductus arteriosus in the failure group was
      significantly higher than in the success group (P<0.05). PaO2, PaO2/FiO2 and
      PaO2/PAO2 in the failure group were significantly lower than in the success group
      (P<0.05). PaCO2 in the failure group was much higher than in the success group
      (P<0.05). Further logistic regression analysis showed that birth weight <1 150 g
      (OR=22.240 95%CI=2.124-232.901), PaCO2>54 mm Hg(OR=9.360, 95%CI=1.958-44.741, and
      PaO2/FiO2 <195 (OR=6.570, 95%CI=1.027-42.003), were the independmend risk factors
      for InSure failure. Furthermore, the duration of oxygen therapy, the total time
      of hospitalization and the incidence of BPD in the failure group were much longer
      and higher than in the success group (P<0.05). CONCLUSIONS: Low birth weight,
      elevated PaCO2 and low PaO2/PiO2 ratio are the risk factors for the failure of
      the InSure method in very preterm infants.

PMID- 24927438
TI  - [Expression of SIRT1 in bone marrow biopsy tissues and its clinical significance
      among children with acute myeloid leukemia].
AB  - OBJECTIVE: To determine the expression level of silent mating-type information
      regulation 2 homologue 1 (SIRT1) in bone marrow biopsy tissues among children
      with acute myeloid leukemia (AML) and analyze its relationship with the prognosis
      of AML patients. METHODS: A retrospective analysis was performed on the clinical
      data of 54 children who were diagnosed with AML between July 2009 and April 2012
      and who underwent bone marrow biopsy at diagnosis. The expression of SIRT1 in
      bone marrow was measured by immunohistochemistry. The 54 patients were divided
      into two groups according to the expression of SIRT1: SIRT1-negative (n=10) and
      SIRT1-positive (n=44). The SIRT1-positive group was further divided into three
      subgroups: SIRT1(+) (n=8), SIRT1(++) (n=7) and SIRT1(+++) (n=29) according to the
      expression levels of SIRT1. Cox multivariate regression analysis was used to
      determine the unfavorable factors for long survival in children with AML.
      RESULTS: The SIRT1(+++) subgroup had a significantly higher mortality than the
      SIRT1-negative group (P<0.05). Compared with the SIRT1-negative group, the SIRT1
      positive group had a significantly lower 2-year overall survival rate (P<0.05)
      and a significantly lower 2-year event-free survival rate (P<0.05). Cox
      multivariate regression analysis showed that positive expression of SIRT1 was an
      unfavorable factor for long-term survival in children with AML, with a risk
      coefficient of 2.071 (95% CI: 1.017-4.219; P=0.045). CONCLUSIONS: SIRT1 is
      overexpressed in some of pediatric AML patients, and the overexpression of SIRT1
      is associated with poor prognosis.

PMID- 24927439
TI  - [ZO-1 gene methylation status and its clinical significance in children with non
      Hodgkin lymphoma].
AB  - OBJECTIVE: To investigate the methylation status of zonula occludens-1 (ZO-1)
      gene promoter and its clinical significance in children with stage IV non-Hodgkin
      lymphoma (NHL) and to provide a basis for further etiological study and early
      diagnosis of this disease. METHODS: Fifty-five children with a confirmed
      diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected
      as the case group, and 20 children with diseases other than hematologic
      malignancies were selected as the control group. Bone marrow samples were
      collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to
      evaluate the methylation status of ZO-1 gene promoter, and the integrated optical
      density (IOD) was determined. RT-PCR was used to measure the mRNA expression of
      ZO-1. RESULTS: MS-PCR showed that the methylated bands of ZO-1 gene promoter were
      found in 39 (70.9%) of 55 patients in the case group before treatment, while no
      ZO-1 gene promoter methylation was detected in the control group. With close
      tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15
      cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment
      were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no
      significant changes in methylation rate in the early and middle phases of
      chemotherapy (P>0.05), but they showed significant changes in methylation rate in
      the late phase of chemotherapy (P<0.05). RT-PCR showed that the NHL cases
      carrying methylated ZO-1 gene had no mRNA expression of ZO-1, while all children
      in the control group had mRNA expression of ZO-1. There was no linear
      relationship between the total number of peripheral blood leukocytes and ZO-1
      gene IOD (r=0.093, P=0.575); a positive correlation was found between the number
      of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, P<0.001).
      CONCLUSIONS: ZO-1 gene shows a hypermethylation status in children with NHL, and
      the methylation level is positively correlated with the number of malignant cells
      in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis,
      outcome assessment, prognostic evaluation, and detection of minimal residual
      disease.

PMID- 24927440
TI  - [Clinical and ATP7A gene analysis of three infants with Menkes disease and
      prenatal diagnosis for a fetus at risk].
AB  - Menkes disease is a rare X-linked recessive disorder characterized by multi
      systemic disorder of copper deficiency caused by ATP7A gene mutation. In this
      study, the clinical and laboratory features of three patients with Menkes disease
      were analyzed. Prenatal diagnosis had been performed for a fetus of a family.
      Three patients were admitted at the age of 8-9 months due to severe epilepsies
      and marked delayed psychomotor development. Significantly light complexion, pudgy
      cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging,
      cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the
      intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2,
      73.5 and 81 mg/L, significantly lower than normal range (210-530 mg/L). c.3914A>G
      (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation,
      c.3265G>T (p.G1089X) was found in case 3. Both of them were firstly found in
      Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks
      of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed
      for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G
      mutation on ATP7A gene was showed. Postnatal genetic analysis and normal
      development confirmed the prenatal diagnosis. 

PMID- 24927441
TI  - [A preliminary study of plasma microRNA levels in children with methylmalonic
      acidemia].
AB  - OBJECTIVE: To screen out differentially expressed microRNAs (miRNAs) in the
      plasma of children with methylmalonic acidemia (MMA), to determine the expression
      of miR-9-1 in plasma and to preliminarily evaluate the significance of miR-9-1 as
      a biomarker in MMA. METHODS: Plasma was obtained from 17 MMA children, 10
      hyperhomocysteinemia (HHcy) children without MMA (HHcy group), and 10 normal
      controls. Of 17 MMA children, 12 had HHcy (MMA+HHcy group), and 5 had no HHcy
      (MMA group). The differentially expressed miRNAs were screened out by miRNA
      microarray. Differentially expressed miR-9-1 was selected, and plasma miR-9-1
      levels were determined by RT-PCR. Urine was collected from MMA patients who
      received vitamin B12 treatment, and plasma miR-9-1 levels were determined by RT
      PCR after treatment. RESULTS: The miRNA microarray analysis showed that 26 miRNAs
      were differentially expressed, among which 16 miRNAs (including miR-9-1) were
      down-regulated over 2 times, while 10 miRNAs were up-regulated over 2 times. The
      MMA+HHcy , MMA and HHcy groups had significantly down-regulated miR-9-1 compared
      with the normal control group (P<0.01). The patients who showed a good response
      to vitamin B12 treatment had significantly increased plasma miR-9-1 levels,
      without significant difference compared with the normal control group.
      CONCLUSIONS: Plasma miR-9-1 is significantly down-regulated in MMA patients, but
      it is significantly up-regulated after vitamin B12 treatment, suggesting that miR
      9-1 may act as a biomarker in monitoring the progression of MMA.

PMID- 24927442
TI  - [Orthogonal factor analysis of metabolic syndrome components in children and
      adolescents in the Xiaoshan District of Hangzhou, China].
AB  - OBJECTIVE: To study the relationship between various metabolic syndrome (MS)
      components in children and adolescents and to explore its potential
      pathophysiological mechanism. METHODS: A total of 1 550 children and adolescents
      aged 7-14 years from the Xiaoshan District of Hangzhou, China were enrolled in
      March 2010. The anthropometric parameters such as height, weight, waist
      circumference (WC), and hip circumference, as well as blood pressure, were
      measured; after adjustment for age and sex, body mass index z score (BMI-z),
      waist circumference z score (WC-z), waist-to-hip ratio (WHp), and waist-to-height
      ratio (WHt) were calculated. Fasting blood samples were collected for
      determination of fasting plasma glucose (FPG), total cholesterol (CHOL),
      triglyceride (TG), high-density lipoproteins (HDL), and low-density lipoproteins
      (LDL). Principal component analysis was used for extraction of factors. RESULTS:
      Principal component analysis revealed 5 uncorrelated factors that cumulatively
      explained 77.76% of the observed variance. Adiposity factor, which accounted for
      23.56% of the variance, was the primary factor; it consisted of 3 variables,
      i.e., WC-z, WHt, and BMI-z, in which WC-z had the highest loading. The remaining
      factors identified were blood lipid factor 1 (TG, CHOL, and LDL), blood pressure
      factor, blood lipid factor 2 (TG and HDL), and blood glucose and WHp factor (FPG
      and WHp). CONCLUSIONS: More than one pathophysiological mechanism could account
      for the development of MS in children and adolescents. Obesity, especially
      central obesity, is the most important factor in the development of MS.
      Dyslipidemia may not fully explain insulin resistance; they may work together in
      MS.

PMID- 24927443
TI  - [Establishment and application of Chinese Pediatric Evaluation of Disability
      Inventory norms in Chongqing, China].
AB  - OBJECTIVE: To establish the Chinese Pediatric Evaluation of Disability Inventory
      (PEDI) norms in Chongqing, China. METHODS: PEDI (English version) was translated
      into Chinese and proof read by back-translation. A total of 1 140 children
      stratified by age were randomly selected from Chongqing and evaluated by the
      Chinese version of the PEDI. The obtained data were statistically analyzed.
      RESULTS: Of 1 140 questionnaires, 1 075 (94.3%) were valid. The data showed that
      the raw and scale scores of PEDI increased with age, but the standard scores did
      not increase with age. The raw, scale, and standard scores on self-care and
      social function scales were significantly lower than American PEDI norms in some
      age periods (P<0.05), but the raw, scale, and standard scores on mobility scale
      were not significantly different from American norms (P>0.05). CONCLUSIONS: The
      PEDI norms in Chongqing have been successfully established, and can be used to
      assess the daily function in children, judge the degree of daily function
      impairment, evaluate the effect of rehabilitation training, and make the
      rehabilitation plan for disabled children.

PMID- 24927444
TI  - [Effect of parental feeding behavior on eating behavior of children aged 1-3
      years].
AB  - OBJECTIVE: To investigate the relationship between the eating behavior of
      children aged 1-3 years and parental feeding behavior and the effect of family
      status on feeding behavior. METHODS: With stratified random sampling, 2 324
      children aged 1-3 years were selected from Shanghai. Questionnaires were filled
      out by their parents or feeders to investigate the basic family information,
      parental feeding behavior, the eating behavior of children, and the basic
      information on children. RESULTS: The eating behavior of children was positively
      correlated with eating environment (r=0.223) and parental monitoring behavior
      (r=0.245) but negatively correlated with parental compulsive behavior (r=-0.264)
      (P<0.01). Moreover, the food preferences of children were negatively correlated
      with parental compulsive behavior (r=-0.569) but positively correlated with
      parental monitoring behavior (r=0.615) and eating environment (r=0.621). The
      emotional undereating of children was positively correlated with parental
      emotional feeding (r=0.259) and parental compulsive behavior (r=0.279). Parental
      monitoring behavior showed significant differences between different families
      (P<0.05). CONCLUSIONS: Parental feeding behavior is closely related to the eating
      behavior of children. Parental feeding behavior may vary across different family
      status.

PMID- 24927445
TI  - [Relationship between Hes-1 and airway inflammation and remodeling in a rat model
      of asthma].
AB  - OBJECTIVE: To study the changes of Hes-1, the target gene of Notch signaling
      pathway, and its relationship with airway inflammation and remodeling in a rat
      model of asthma. METHODS: Forty-eight rats were randomly divided into an asthma
      group and a control group. The rats in the asthma group were sensitized and
      challenged by ovalbumin (OVA), and normal saline was used in the control group.
      Two groups were further divided into 3 subgroups according to time points after
      challenging, i.e. 4 weeks, 8 weeks and 12 weeks (n=8 rats each). Pathological
      changes of lungs were observed by light microscopy and the thickness of bronchial
      smooth muscle layer (Wam) was measured. The levels of IL-4 and INF-gamma in rat
      serum and bronchoalveolar lavage fluids (BALF) were measured using ELISA.
      Expression levels of Hes-1 protein and mRNA were determined by
      immunohistochemistry and quantitative real-time PCR respectively. RESULTS:
      Together with the extension of challenging, the Wam of rats in the asthma group
      increased, a decrease of INF-gamma level and an increase of IL-4 level in serum
      and BALF were also observed, and the differences were statistically significant
      compared with those in the corresponding control group (P<0.05). Hes-1 protein
      and mRNA levels also increased gradually after OVA challenging and were higher
      than those in the control group (P<0.05). The levels of Hes-1 protein and mRNA
      were positively correlated with Wam and IL-4 in serum and BALF, but were
      inversely correlated with INF-gamma in serum and BALF (P<0.05). CONCLUSIONS:
      Levels of Hes-1 protein and mRNA increased, which were closely related with the
      levels of airway inflammatory factors and remodeling of airway smooth muscle. Hes
      1 may play an important role in the pathogenesis of asthma.

PMID- 24927446
TI  - [Febrile infection-related epilepsy syndrome in two children].

PMID- 24927447
TI  - [Atipical meningococcal meningitis in an infant].

PMID- 24927448
TI  - [Thyroid storm in a newborn infant].

PMID- 24927449
TI  - Efficient sample preparation from complex biological samples using a sliding lid
      for immobilized droplet extractions.
AB  - Sample preparation is a major bottleneck in many biological processes.
      Paramagnetic particles (PMPs) are a ubiquitous method for isolating analytes of
      interest from biological samples and are used for their ability to thoroughly
      sample a solution and be easily collected with a magnet. There are three main
      methods by which PMPs are used for sample preparation: (1) removal of fluid from
      the analyte-bound PMPs, (2) removal of analyte-bound PMPs from the solution, and
      (3) removal of the substrate (with immobilized analyte-bound PMPs). In this
      paper, we explore the third and least studied method for PMP-based sample
      preparation using a platform termed Sliding Lid for Immobilized Droplet
      Extractions (SLIDE). SLIDE leverages principles of surface tension and patterned
      hydrophobicity to create a simple-to-operate platform for sample isolation
      (cells, DNA, RNA, protein) and preparation (cell staining) without the need for
      time-intensive wash steps, use of immiscible fluids, or precise pinning
      geometries. Compared to other standard isolation protocols using PMPs, SLIDE is
      able to perform rapid sample preparation with low (0.6%) carryover of
      contaminants from the original sample. The natural recirculation occurring within
      the pinned droplets of SLIDE make possible the performance of multistep cell
      staining protocols within the SLIDE by simply resting the lid over the various
      sample droplets. SLIDE demonstrates a simple easy to use platform for sample
      preparation on a range of complex biological samples. 

PMID- 24927451
TI  - Editorial.

PMID- 24927450
TI  - Chondroitin sulfate coatings display low platelet but high endothelial cell
      adhesive properties favorable for vascular implants.
AB  - This study highlights the advantages of chondroitin sulfate (CS) as a sublayer
      combining selective low-fouling properties, low-platelet adhesion and pro
      adhesive properties on endothelial cells, making CS promising for vascular graft
      applications. These properties were evaluated by comparing CS with well-known low
      fouling coatings such as poly(ethylene glycol) (PEG) and carboxymethylated
      dextran (CMD), which were covalently grafted on primary amine-rich plasma
      polymerized (LP) films. Protein adsorption studies by quartz crystal microbalance
      with dissipation monitoring (QCM-D) and fluorescence measurements showed that CS
      is as effective as PEG in reducing fibrinogen adsorption (~90% reduction). CS
      also largely reduced adsorption of bovine serum albumin (BSA) as well as fetal
      bovine serum (FBS) but to a lower extent than PEG and CMD surfaces (72% vs 85%
      for BSA and 66% vs 89% for FBS). Whole blood perfusion assays indicated that,
      while LP surfaces were highly reactive with platelets, PEG, CMD, and CS grafted
      surfaces drastically decreased platelet adhesion and activation to levels
      significantly lower than polyethylene terephthalate (PET) surfaces. Finally,
      while human umbilical vein endothelial cell (HUVEC) adhesion and growth were
      found to be very limited on PEG and CMD, they were significantly increased on CS
      compared to that on bare PET and reached similar values as those for tissue
      culture polystyrene positive controls. Interestingly, HUVEC retention during
      perfusion with blood was found to be excellent on CS but poor on PET. Overall,
      our results suggest that the CS surface has the advantage of promoting HUVEC
      growth and resistance to flow-induced shear stress while preventing fibrinogen
      and platelet attachment. Such a nonthrombogenic but endothelial-cell adhesive
      surface is thus promising to limit vascular graft occlusion.

PMID- 24927452
TI  - Pharmacotherapy of mania: A review.
AB  - The management of mania is an important and common clinical challenge. A wide
      array of psychopharmacological alternatives is available, diverse in their
      mechanism of action. They include lithium, the antipsychotics, anticonvulsants
      and others. With the exception of lithium, all these agents have been borrowed
      from other indications. The wide variety of therapeutic options does not help to
      clarify the primary pathophysiological mechanisms operative in bipolar disorder.
      While the development of novel therapeutic agents increases the available
      armamentarium, there is little clarity as to the place of the novel agents in
      treatment regimens. A further issue in the treatment of mania is the significant
      divergence of opinion as to choice of first-line antimanic therapy. This paper
      attempts to review the evidence of efficacy of the various antimanic agents, with
      a focus on the novel anticonvulsant and neuroleptic drugs, and to discuss the
      data available on these novel therapeutic options. ( Int J Psych Clin Pract 2000;
      4: 171 - 193). 

PMID- 24927453
TI  - Recurrent brief depression: A frequent syndrome in clinical practice.
AB  - Recurrent brief depression (RBD) is not a new artificial group of depression
      syndromes, but an important, frequently overlooked and clearly identified
      subcategory of depressive disorders. The symptoms do not differ from major
      depression; however, the duration of the brief episodes usually lasts 1 &#45 3
      days. The patient can suffer from both brief and longer manifestations of
      depression and therefore qualify for both diagnoses: major depression on the one
      hand/or RBD on the other. If the patient suffers from both conditions the case is
      more severe, with higher social impairment and higher suicidal risk.
      Epidemiological studies carried out in different parts of the world indicated a
      prevalence rate of RBD of between 5% and 10% of patients seeking help in general
      practice. Unfortunately there is no clear treatment as yet established for RBD,
      although about 50% of these patients are given psychotropic drugs by
      practitioners. Controlled trials with antidepressants did not show a beneficial
      effect and there is no hint in the literature as to whether psychological
      therapies might be helpful. There is a need for further treatment studies in this
      important form of depression, which is categorizable within the depressive
      spectrum. ( Int J Psych Clin Pract 2000; 4: 195-199). 

PMID- 24927454
TI  - Reboxetine, the first selective noradrenaline reuptake inhibitor antidepressant:
      Efficacy and tolerability in 2613 patients.
AB  - INTRODUCTION: Reboxetine is the first available selective noradrenaline re-uptake
      inhibitor (selective NRI). This paper gives an overview of its antidepressant
      efficacy and tolerability in eight randomized double-blind, multicentre clinical
      trials. The clinical profile of reboxetine is also compared with that of the
      tricyclic antidepressants (TCAs) desipramine and imipramine and the selective
      serotonin re-uptake inhibitor (SSRI) fluoxetine. METHODS: Pooled data were
      analysed from seven short-term (4 &#45 8 weeks) and one long-term (up to 1 year)
      trials comparing reboxetine with placebo, imipramine, desipramine or fluoxetine.
      The tolerability of reboxetine was evaluated in 2613 patients with major
      depression or dysthymia. Data from 1959 patients with major depressive disorder
      were included to assess drug efficacy. Efficacy was principally assessed using
      the Hamilton Depression Rating Scale (HAM-D). RESULTS: Reboxetine was more
      effective than placebo in three of four short-term trials, and it was as
      effective as fluoxetine, imipramine and desipramine. In long-term treatment,
      reboxetine was more effective than placebo in preventing relapse ( &#83 50%
      increase in HAM-D) and recurrence (HAM-D total score &#104 10). In a subset of
      severely depressed patients, reboxetine was as effective as imipramine and
      significantly more effective than fluoxetine. Reboxetine was as effective as
      imipramine in the elderly, but better tolerated. The most common adverse events
      among the 1503 patients (adults and elderly) who received reboxetine were dry
      mouth (22%), constipation (15%), sweating (12%) and insomnia (11%). Overall,
      reboxetine was well tolerated, as well as the SSRI fluoxetine and better than the
      TCAs imipramine and desipramine. CONCLUSIONS: Reboxetine is effective and well
      tolerated in the short and long-term treatment of depression. It is as well
      tolerated as fluoxetine and better than imipramine and desipramine. ( Int J Psych
      Clin Pract 2000; 4: 201 - 208).

PMID- 24927455
TI  - The efficacy of zotepine in treating acute negative symptoms of schizophrenia:
      The results of a meta-analysis.
AB  - INTRODUCTION: Zotepine is a unique antipsychotic drug, having effects which are
      both antiserotonergic and antidopaminergic that may make it more effective in the
      treatment of negative symptoms of schizophrenia than more conventional agents.
      METHOD: A meta-analysis was performed on the effect of zotepine on the negative
      symptoms in seven double-blind studies, as measured by the SANS scale. RESULTS:
      Of the trials selected for this meta-analysis, one showed significant improvement
      in acute negative symptoms in favour of zotepine. Negative symptoms measured in
      the other trials showed trends in favour of zotepine, except for one study where
      the trend was in favour of perazine. The meta-analysis showed zotepine to be
      significantly better then either placebo or conventional antipsychotic
      comparators using the standardized treatment difference methodology, and it
      confirmed the results from a previous study using patients with predominantly
      negative symptoms. CONCLUSION: Zotepine may have a place in the treatment of this
      group of patients where conventional antipsychotic drugs have had little effect.
      ( Int J Psych Clin Pract 2000; 4: 209 - 214).

PMID- 24927456
TI  - Do depressive patients with family history of dementia constitute a separate
      group? A case report study.
AB  - INTRODUCTION: Recently it has been suggested that patients with both depression
      and a family history of dementia are seven times as likely to develop Alzheimer's
      disease as are controls. METHOD: Fifty patients aged 21 &#45 60 years suffering
      from DSM-IV Major Depression entered the study; three of them (6%) had a positive
      family history of dementia. Diagnosis was by SCAN v 2.0. The family history
      method was used to record family history. All depressed patients were
      investigated with the Dexamethasone Suppression Test (DST), brain SPECT, electro
      oculogram (EOG), flash-electroretinogram (f-ERG) and Pattern-Reversal Visual
      Evoked Potentials (PR-VEPs). Student's t-test was used to analyse the results.
      All patients with positive family history had atypical features. RESULTS: Two of
      them suffered from borderline personality disorder, in comparison to eight in the
      remainder of the sample and five in the rest of the atypicals. The age of onset
      of depression was lower. DST, SPECT, EOG and PR-VEPs findings were similar
      between groups. The only significant finding concerned the latency of the bs wave
      of the scotopic ERG (P < 0.01), but even in this, patients with positive history
      did not differ from the rest of the atypical patients. CONCLUSION: The present
      study provided limited data connecting atypical features of depression,
      personality traits, psychological stressors, hypercortisolaemia and family
      history of dementia. Further research with larger samples is essential. ( Int J
      Psych Clin Pract 2000; 4: 215 - 222).

PMID- 24927457
TI  - Transcranial magnetic stimulation is effective in the treatment of relapse of
      depression.
AB  - INTRODUCTION: The aim of this preliminary report is to demonstrate the efficacy
      of rapid transcranial magnetic stimulation (rTMS) in the treatment of relapsed
      major depressive disorder (MDD) patients. METHODS: Four patients with major
      depressive disorder who were successfully treated with rTMS received a second
      course of rTMS treatment. Patients were evaluated with the Hamilton Depression
      Rating Scale &#45 21 items, the Brief Psychiatric Rating Scale, the Global
      Depression Scale and the Global Assessment Scale in both trials. The statistical
      analysis was performed with paired t-tests and chi squares. RESULTS: Clinical
      ratings demonstrated a significant improvement at the end of both trials. No
      significant differences were found between the ratings at the end of the
      treatment courses. CONCLUSION: rTMS was successfully used in the treatment of
      relapsed MDD patients who had previously responsed to rTMS. ( Int J Psych Clin
      Pract 2000; 4: 223 - 226).

PMID- 24927458
TI  - Private psychiatry in Switzerland.
AB  - INTRODUCTION: Two-thirds of Swiss psychiatrists are engaged, either exclusively
      or partially, in private practice, a proportion that is higher than in other
      countries. METHOD: A questionnaire survey of 1000 psychiatrists was carried out.
      RESULTS: Psychiatrists in private practice display a greater degree of clinical
      activity, mainly with individuals, than do psychiatrists employed by public
      institutions; and they work principally within two practice profiles,
      psychoanalytical and generalist, and much less in the biological profile. They
      show a preference for the psychological model, mostly in a psychoanalytical
      orientation. Psychiatrists who have a mixed privatepublic practice &#45 more than
      half of them &#45 are even more psychoanalytically oriented than psychiatrists
      working exclusively in private practice. They act as an interface between the
      public and private sectors, playing a pivotal role as guardians of
      psychoanalysis, proclaiming its principles to psychiatric residents. CONCLUSION:
      With the transformations taking place in the health care system, new care
      concepts are being developed, there is a wider variety of theoretical
      orientations, and the profession is therefore undergoing substantial changes. (
      Int J Psych Clin Pract 2000; 4: 227 - 232).

PMID- 24927459
TI  - How urgent is urgent? Analysing urgent out-patient referrals to an adult
      psychiatric service.
AB  - INTRODUCTION: It was noticed that over some years the number of referrals to the
      outpatient clinic (from various sources) which were marked 'urgent' had
      increased. We aimed to examine who makes these urgent referrals and the clinical
      factors associated with 'urgent' status. METHODS: A sample of 201 referrals over
      a 26-month period was examined. Details of the referral requests were collected
      using a specially designed form. After each 'urgent' assessment, the referral was
      scored for appropriateness. This gave an indication of the agreement between
      referrer and clinic doctor as to what should constitute an &#164 urgent'
      referral. RESULTS: The majority of urgent referrals were from community
      psychiatric nurses, who, together with psychiatric social workers, make the most
      appropriate referrals. The more appropriate referrals clearly specified the
      clinical factors associated with urgent need for review. Patients regarded as
      suicidal were not associated with significantly higher appropriateness scores.
      CONCLUSION: Referrers should try and make 'urgent' outpatient requests as
      specific as possible: more clinical detail gives a clearer picture to the clinic
      doctor. Telephone consultations with general practitioners may help to ascertain
      a clearer picture of urgent requests if detail is lacking. Health professionals
      may all benefit from education in suicidal risk assessment. ( Int J Psych Clin
      Pract 2000; 4: 233 - 235).

PMID- 24927460
TI  - Priapism associated with risperidone treatment.
AB  - Priapism is the occurrence of sustained and painful erection that does not result
      from sexual desire and fails to subside despite orgasm. It is often accompanied
      by pain and tenderness. The aetiologies are idiopathic, alcohol abuse, drug
      therapy, perinatal trauma and sickle-cell anaemia. It is a very rare adverse
      effect of psychotropic medications, due to alphaadrenergic receptor blockade.
      Priapism is reported in a 19-year-old physically healthy mental patient after 4
      days of risperidone treatment 2 mg/day. ( Int J Psych Clin Pract 2000; 4: 237 -
      239). 

PMID- 24927461
TI  - Risperidone treatment of neuroleptic-induced tardive extrapyramidal symptoms.
AB  - Tardive extrapyramidal symptoms (EPS) induced by neuroleptic treatment, and
      particularly EPS which persist after withdrawal of the drugs, are clinically
      serious problems. We describe a patient with four types of tardive and persistent
      EPS such as dystonia, dyskinesia, choreatic movement and myoclonus, induced by
      haloperidol. These EPS were remarkably inhibited by 3 mg/day risperidone. This is
      the first published case demonstrating simultaneous development of these four
      types of tardive EPS induced by a neuroleptic and then reduced by low-dose
      risperidone treatment. ( Int J Psych Clin Pract 2000; 4: 241 - 243). 

PMID- 24927462
TI  - Delusional misidentification secondary to perceptual abnormality: An unusual case
      of Capgras syndrome.
AB  - Capgras syndrome is the commonest of the delusional misidentification syndromes,
      occurring in 1 &#45 5% of psychotic patients. This case of a Capgras syndrome was
      secondary to an abnormal percept (auditory hallucination). Capgras syndrome is
      not a symptom specific to abnormalities of face recognition. ( Int J Psych Clin
      Pract 2000; 4: ). 

PMID- 24927463
TI  - Risperidone for non-cognitive symptoms of dementia.
AB  - A case of a 95-year-old man suffering from dementia and additional noncognitive
      symptoms is reported. Sleep disturbances and restlessness were treated with
      several psychotropics including polycyclic antidepressants and conventional
      neuroleptics without success. Receiving this treatment, the patient became
      increasingly confused and markedly aggressive. In addition, he developed marked
      extrapyramidal side-effects and became severely sedated during the day. Swtiching
      to risperidone resulted in a reduction of many of these symptoms. Finally,
      receiving risperidone, all non-cognitive symptoms and all side-effects completely
      disappeared. Further, this case shows the importance of an adequate
      psychopharmacologic training for non-psychiatric physicians who often treat
      elderly mentally ill in nursing homes and general hospitals. ( Int J Psych Clin
      Pract 2000; 4: 249 - 251). 

PMID- 24927464
TI  - A patient who changed my practice: The case for patient-based evidence versus
      trial-based evidence.
AB  - A patient who has an unequivocal psychotic illness within the schizoaffective
      spectrum is described. Over the course of the past 10 years she has convinced me
      that her way of looking at her own illness, particularly her refusal to take
      medication, has merits that cannot be dismissed as the overwrought workings of a
      disturbed mind. Her experience has helped me to understand that it is still
      possible to be an advocate of evidence-based medicine and yet accommodate the
      wishes of patients in a way that sometimes elevates personal patient-based
      evidence above that of external criteria. ( Int J Psych Clin Pract 2000; 4: 253 -
      255). 

PMID- 24927467
TI  - Clinical evidence of the relationship between aspirin and breast cancer risk
      (review).
AB  - In the search for new therapeutic alternatives against cancer, either as a
      preventive treatment or for advanced stages, it is common to appeal to well-known
      drugs used for the treatment of other diseases that may interfere with the
      metabolic pathways involved in carcinogenesis. Non-steroidal anti-inflammatory
      drugs (NSAIDs) display anticancer activity through the inhibition of the COX-2
      enzyme, triggering processes such as apoptosis, a reduction in proliferation and
      inhibition of carcinogenesis. Breast cancer is a neoplasm with the highest
      incidence and mortality rate among young women worldwide. Epidemiologic data have
      shown that drugs such as NSAIDs, particularly aspirin, reduce the relative risk
      of breast cancer. However, in the subgroup of responsive patients, dose, time and
      frequency of use have not yet been established. Here, we review the reports
      published during the last 10 years regarding the relationship between breast
      cancer and aspirin. 

PMID- 24927468
TI  - Molecular dynamics study of the diffusivity of a hydrophobic drug Cucurbitacin B
      in pseudo-poly(ethylene oxide-b-caprolactone) micelle environments.
AB  - Isobaric-isothermal molecular dynamics simulation was used to study the diffusion
      of a hydrophobic drug Cucurbitacin B (CuB) in pseudomicelle environments
      consisting of poly(ethylene oxide-b-caprolactone) (PEO-b-PCL) swollen by various
      amounts of water. Two PEO-b-PCL configurations, linear and branched, with the
      same total molecular weight were used. For the branched configuration, the block
      copolymer contained one linear block of PEO with the same molecular weight as
      that of the PEO block used in the linear configuration but with one end
      connecting to three PCL blocks with the same chain length, hereafter denoted PEO
      b-3PCL. Regardless of the configuration, the simulation results showed that the
      diffusivity of CuB was insensitive to the water concentration up to ~8 wt % while
      that of water decreased with an increasing water concentration. The diffusivity
      of CuB (10(-8) cm(2)/s) was 3 orders of magnitude lower than that of water (10(
      5) cm(2)/s). This is attributed to the fact that CuB relied on the wiggling
      motion of the block copolymers to diffuse while water molecules diffused via a
      hopping mechanism. The rates at which CuB and water diffused into PEO-b-PCL were
      twice those in PEO-b-3PCL because the chain mobility and the degree of swelling
      are higher and there are fewer intermolecular hydrogen bonds in the case of PEO-b
      PCL. The velocity autocorrelation functions of CuB show that the free volume
      holes formed by PEO-b-3PCL are more rigid than those formed by PEO-b-PCL, making
      CuB exhibit higher-frequency collision motion in PEO-b-3PCL than in PEO-b-PCL,
      and the difference in frequency is insensitive to water concentration. 

PMID- 24927469
TI  - Effect of lignin content and subunit composition on digestibility in clones of
      timothy (Phleum pratense L.).
AB  - Lignin amount and subunit composition were analyzed from stems and leaf sheaths
      of timothy (Phleum pratense L.) clones of different in vitro digestibility.
      Lignin concentration in stems and leaf sheaths was higher in clones of low
      digestibility than those of high digestibility. No change in lignin concentration
      occurred in stems as digestibility decreased. Intriguingly, the lignin
      concentration was lower and the syringyl/guaiacyl (S/G) ratio was higher in stems
      compared to leaf sheaths at all developmental stages studied. The developmental
      associated decrease in digestibility correlated with the increase in S units in
      lignin in stems and leaf sheaths and in the amounts of p-coumaric acid and
      ferulic acid residues in the cell wall of stems. Yields of copper oxidation
      products increased in stems during maturation indicating qualitative changes in
      the lignin structure. This correlated strongly with the developmentally linked
      decrease in digestibility. The information obtained is valuable for breeding and
      for DNA marker development. 

PMID- 24927471
TI  - Online CBT for preschool anxiety disorders: a randomised control trial.
AB  - The aim of this study was to investigate the efficacy of an internet-based,
      therapist assisted, parent-focussed, CBT program for preschoolers with anxiety
      disorders. Fifty-two children aged 3-6 years were randomly allocated into
      internet treatment (NET) and waitlist control (WLC) groups. Parents completed
      diagnostic interviews and online questionnaires at pre-treatment, post-treatment
      and 6-month follow-up. Results at post-treatment showed a significantly greater
      reduction in clinical severity, anxiety symptoms and internalising behaviour, as
      well as a greater increase in overall functioning for children in the NET
      compared to the WLC condition. However, group differences were not evident from
      pre- to post-treatment on the percentages of children who lost their primary
      anxiety diagnosis or who lost all anxiety diagnoses. At post-treatment for the
      completer sample, 39.1% of the NET children compared to 25.9% of the WLC were
      free of their primary diagnosis. At 6-month follow-up, treatment gains were
      maintained in the case of overall functioning and further improved upon with
      respect to clinical severity, anxiety symptoms and internalising behaviour. By 6
      month follow-up for the completer sample, 70.6% of children were free of their
      primary diagnosis. The results suggest that an internet program for preschool
      anxiety is feasible, efficacious and well received by parents. AUSTRALIAN
      CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12612000139875.

PMID- 24927470
TI  - Exploring design requirements for repurposing dental virtual patients from the
      web to second life: a focus group study.
AB  - BACKGROUND: Since their inception, virtual patients have provided health care
      educators with a way to engage learners in an experience simulating the
      clinician's environment without danger to learners and patients. This has led
      this learning modality to be accepted as an essential component of medical
      education. With the advent of the visually and audio-rich 3-dimensional multi
      user virtual environment (MUVE), a new deployment platform has emerged for
      educational content. Immersive, highly interactive, multimedia-rich, MUVEs that
      seamlessly foster collaboration provide a new hotbed for the deployment of
      medical education content. OBJECTIVE: This work aims to assess the suitability of
      the Second Life MUVE as a virtual patient deployment platform for undergraduate
      dental education, and to explore the requirements and specifications needed to
      meaningfully repurpose Web-based virtual patients in MUVEs. METHODS: Through the
      scripting capabilities and available art assets in Second Life, we repurposed an
      existing Web-based periodontology virtual patient into Second Life. Through a
      series of point-and-click interactions and multiple-choice queries, the user
      experienced a specific periodontology case and was asked to provide the optimal
      responses for each of the challenges of the case. A focus group of 9
      undergraduate dentistry students experienced both the Web-based and the Second
      Life version of this virtual patient. The group convened 3 times and discussed
      relevant issues such as the group's computer literacy, the assessment of Second
      Life as a virtual patient deployment platform, and compared the Web-based and
      MUVE-deployed virtual patients. RESULTS: A comparison between the Web-based and
      the Second Life virtual patient revealed the inherent advantages of the more
      experiential and immersive Second Life virtual environment. However, several
      challenges for the successful repurposing of virtual patients from the Web to the
      MUVE were identified. The identified challenges for repurposing of Web virtual
      patients to the MUVE platform from the focus group study were (1) increased case
      complexity to facilitate the user's gaming preconception in a MUVE, (2) necessity
      to decrease textual narration and provide the pertinent information in a more
      immersive sensory way, and (3) requirement to allow the user to actuate the
      solutions of problems instead of describing them through narration. CONCLUSIONS:
      For a successful systematic repurposing effort of virtual patients to MUVEs such
      as Second Life, the best practices of experiential and immersive game design
      should be organically incorporated in the repurposing workflow (automated or
      not). These findings are pivotal in an era in which open educational content is
      transferred to and shared among users, learners, and educators of various open
      repositories/environments.

PMID- 24927472
TI  - Volume and mass doubling times of persistent pulmonary subsolid nodules detected
      in patients without known malignancy.
AB  - PURPOSE: To evaluate volume doubling time (VDT) and mass doubling time (MDT) of
      persistent pulmonary subsolid nodules (SSNs) followed-up with low-dose (LD)
      computed tomography (CT) in patients without a history of malignancy. MATERIALS
      AND METHODS: This retrospective institutional review board-approved study, with
      waiver of patient informed consent, included 97 SSNs in 97 patients (45 men, 52
      women; median age, 58 years; range, 37-87 years) in whom at least two LD CT scans
      were obtained, with 3-month or longer follow-up interval and median follow-up of
      633 days. SSNs were categorized into pure ground-glass nodules (GGNs) (group A),
      part-solid GGNs with solid components of 5 mm or smaller (group B), and part
      solid GGNs with solid components larger than 5 mm (group C). Three-dimensional
      manual segmentation for all SSNs was performed on initial and latest follow-up LD
      CT scans; subsequently, VDTs and MDTs were calculated and were compared among
      groups by using Kruskal-Wallis test, followed by the Dunn procedure with
      Bonferroni correction for volume-growing SSNs and mass-growing SSNs. RESULTS:
      Volume growth was thus: 12 of 63 SSNs (19%), group A; nine of 23 SSNs (39%),
      group B; and eight of 11 SSNs (73%), group C. Median VDT was thus: 1832.3 days
      (range, 1230.7-4537.3 days), group A; 1228.5 days (range, 934.7-4617.7 days),
      group B; and 759.0 days (range, 376.4-941.5 days), group C. Mass growth was thus:
      17 of 63 SSNs (27%), group A; 11 of 23 SSNs (48%), group B; and nine of 11 SSNs
      (82%), group C. Median MDT was 1556.1 days (range, 642.5-3564.5 days) for group
      A, 1199.9 days (range, 838.6-2578.7 days) for group B, and 627.7 days (range,
      340.0-921.2 days) for group C. Median VDTs and MDTs of groups A and B were
      significantly longer than those of group C (P < .01). CONCLUSION: Pure GGNs and
      part-solid GGNs with solid components of 5 mm or smaller show significantly
      longer VDTs and MDTs than do part-solid GGNs with solid components larger than 5
      mm. Online supplemental material is available for this article.

PMID- 24927473
TI  - Regional but not global brain damage contributes to fatigue in multiple
      sclerosis.
AB  - PURPOSE: To use magnetic resonance (MR) imaging and advanced analysis to assess
      the role of lesions in normal-appearing white matter ( NAWM normal-appearing
      white matter ) and gray matter ( GM gray matter ) damage, global versus regional
      damage, and atrophy versus microstructural abnormalities in the pathogenesis of
      fatigue in multiple sclerosis ( MS multiple sclerosis ). MATERIALS AND METHODS:
      Local ethics committee approval and written informed consent were obtained. Dual
      echo, double inversion-recovery, high-resolution T1-weighted and diffusion-tensor
      ( DT diffusion tensor ) MR was performed in 31 fatigued patients, 32 nonfatigued
      patients, and 35 control subjects. Global and regional atrophy and DT diffusion
      tensor MR measures of damage to lesions, NAWM normal-appearing white matter , and
      GM gray matter were compared (analysis of variance). RESULTS: Lesional, atrophy,
      and DT diffusion tensor MR measures of global damage to brain, white matter ( WM
      white matter ), and GM gray matter did not differ between fatigued and
      nonfatigued patients. Compared with nonfatigued patients and control subjects,
      fatigued patients experienced atrophy of the right side of the accumbens (mean
      volume +/- standard deviation, 0.37 mL +/- 0.09 in control subjects; 0.39 mL +/-
      0.1 in nonfatigued patients; and 0.33 mL +/- 0.09 in fatigued patients), right
      inferior temporal gyrus ( ITG inferior temporal gyrus ) (Montreal Neurological
      Institute [ MNI Montreal Neurological Institute ] coordinates: 51, -51, -11; t
      value, 4.83), left superior frontal gyrus ( MNI Montreal Neurological Institute
      coordinates: -10, 49, 24; t value, 3.40), and forceps major ( MNI Montreal
      Neurological Institute coordinates: 11, -91, 18; t value, 3.37). They also had
      lower fractional anisotropy ( FA fractional anisotropy ) of forceps major ( MNI
      Montreal Neurological Institute coordinates: -17, -78, 6), left inferior fronto
      occipital fasciculus ( MNI Montreal Neurological Institute coordinates: -25, 2, 
      11), and right anterior thalamic radiation ( ATR anterior thalamic radiation ) (
      MNI Montreal Neurological Institute coordinates: 11, 2, -6) (P < .05, corrected).
      More lesions were found at T2-weighted imaging in fatigued patients.
      Multivariable model was used to identify right ITG inferior temporal gyrus
      atrophy (odds ratio, 0.83; 95% confidence interval [ CI confidence interval ]:
      0.82, 0.97; P = .009) and right ATR anterior thalamic radiation FA fractional
      anisotropy (odds ratio, 0.74; 95% CI confidence interval : 0.61, 0.90; P = .003)
      as covariates independently associated with fatigue (C statistic, 0.85).
      CONCLUSION: Damage to strategic brain WM white matter and GM gray matter regions,
      in terms of microstructural abnormalities and atrophy, contributes to
      pathogenesis of fatigue in MS multiple sclerosis , whereas global lesional, WM
      white matter , and GM gray matter damage does not seem to have a role.

PMID- 24927474
TI  - Characteristic electronic perturbation by asymmetric arrangements of p
      aminophenyl substituents in free-base porphyrins.
AB  - We have investigated the perturbed electronic properties of meso-substituted free
      base porphyrins with symmetric and asymmetric arrangements of substituents using
      time-resolved spectroscopic measurements and theoretical calculations. The extent
      of electronic perturbation by substituents in meso-substituted porphyrins is
      mainly affected by the isoenergetic condition of frontier MOs of porphine and
      substituent units, nonorthogonal geometry, and geometrical arrangement of
      substituents. By using the asymmetric arrangements of p-aminophenyl and
      pentafluorophenyl substituents, we can induce the electron-rich condition on the
      porphine unit and the intramolecular charge transfer character in the excited
      state. On the basis of this work, we can gain further insight into the energetic
      and geometric factors of substituents, the interaction between porphine and
      substituent units, and the perturbed photophysical and electronic properties by
      substituents, which provides a firm basis for further understanding of the
      catalytic activities or photophysical properties of porphyrins in porphyrin-based
      molecular catalysts and electronics. 

PMID- 24927475
TI  - Structured syncope care pathways based on lean six sigma methodology optimises
      resource use with shorter time to diagnosis and increased diagnostic yield.
AB  - AIMS: To conduct a pilot study on the potential to optimise care pathways in
      syncope/Transient Loss of Consciousness management by using Lean Six Sigma
      methodology while maintaining compliance with ESC and/or NICE guidelines.
      METHODS: Five hospitals in four European countries took part. The Lean Six Sigma
      methodology consisted of 3 phases: 1) Assessment phase, in which baseline
      performance was mapped in each centre, processes were evaluated and a new
      operational model was developed with an improvement plan that included best
      practices and change management; 2) Improvement phase, in which optimisation
      pathways and standardised best practice tools and forms were developed and
      implemented. Staff were trained on new processes and change-management support
      provided; 3) Sustaining phase, which included support, refinement of tools and
      metrics. The impact of the implementation of new pathways was evaluated on number
      of tests performed, diagnostic yield, time to diagnosis and compliance with
      guidelines. One hospital with focus on geriatric populations was analysed
      separately from the other four. RESULTS: With the new pathways, there was a 59%
      reduction in the average time to diagnosis (p = 0.048) and a 75% increase in
      diagnostic yield (p = 0.007). There was a marked reduction in repetitions of
      diagnostic tests and improved prioritisation of indicated tests. CONCLUSIONS:
      Applying a structured Lean Six Sigma based methodology to pathways for syncope
      management has the potential to improve time to diagnosis and diagnostic yield.

PMID- 24927476
TI  - Evaluation of the role of dynamic contrast-enhanced MR imaging for patients with
      BI-RADS 3-4 microcalcifications.
AB  - OBJECTIVE: The purpose of study was to prospectively evaluate the diagnostic
      performance of dynamic contrast-enhanced MR imaging in the differentiation of
      malignant lesions from benign ones in patients with BI-RADS 3-4
      microcalcifications detected by mammography. MATERIALS AND METHODS: 93 women with
      100 microcalcifications had undergone breast MRI from June 2010 to July 2013.
      Subsequently, 91 received open biopsy and 2 received stereotactic vacuum-assisted
      biopsy. All results were compared with histological findings. The PPV, NPV and
      area under curve (AUC) of the mammography and breast MRI were calculated.
      RESULTS: There were 31 (31.0%) BI-RADS 3 microcalcifications and 69 (69.0%) BI
      RADS 4. The PPV and NPV of mammography is 65.2% (45/69) and 90.3% (28/31). The
      PPV and NPV of breast MRI was 90.2% (46/51) and 95.9% (47/49). Among 31 BI-RADS 3
      microcalcifications, the PPV and NPV of breast MRI was 100% (3/3) and 100%
      (28/28). Among 69 BI-RADS 4 microcalcifications, the PPV and NPV of breast MRI
      was 89.6% (43/48) and 90.5% (19/21). The AUC of mammography and breast MRI
      assessment were 0.738 (95% CI, 0.639-0.837) and 0.931 (95% CI, 0.874-0.988)
      (p<0.05). CONCLUSION: Dynamic contrast-enhanced MR imaging of breast is able to
      be applied to predict the risk of malignance before follow-up for BI-RADS 3
      microcalcifications and biopsy for BI-RADS 4 microcalcifications.

PMID- 24927477
TI  - RAMClust: a novel feature clustering method enables spectral-matching-based
      annotation for metabolomics data.
AB  - Metabolomic data are frequently acquired using chromatographically coupled mass
      spectrometry (MS) platforms. For such datasets, the first step in data analysis
      relies on feature detection, where a feature is defined by a mass and retention
      time. While a feature typically is derived from a single compound, a spectrum of
      mass signals is more a more-accurate representation of the mass spectrometric
      signal for a given metabolite. Here, we report a novel feature grouping method
      that operates in an unsupervised manner to group signals from MS data into
      spectra without relying on predictability of the in-source phenomenon. We
      additionally address a fundamental bottleneck in metabolomics, annotation of MS
      level signals, by incorporating indiscriminant MS/MS (idMS/MS) data implicitly:
      feature detection is performed on both MS and idMS/MS data, and feature-feature
      relationships are determined simultaneously from the MS and idMS/MS data. This
      approach facilitates identification of metabolites using in-source MS and/or
      idMS/MS spectra from a single experiment, reduces quantitative analytical
      variation compared to single-feature measures, and decreases false positive
      annotations of unpredictable phenomenon as novel compounds. This tool is released
      as a freely available R package, called RAMClustR, and is sufficiently versatile
      to group features from any chromatographic-spectrometric platform or feature
      finding software. 

PMID- 24927479
TI  - Highly porous conjugated polymers for selective oxidation of organic sulfides
      under visible light.
AB  - High surface area porous conjugated polymers were synthesized via the high
      internal phase emulsion polymerization technique and micropore engineering as
      efficient heterogeneous photocatalysts for highly selective oxidation of organic
      sulfides to sulfoxides under visible light. 

PMID- 24927478
TI  - Whole genome wide expression profiles on germination of Verticillium dahliae
      microsclerotia.
AB  - Verticillium dahliae is a fungal pathogen causing Verticillium wilt on a range of
      economically important crops. Microsclerotia are its main survival and dormancy
      structures and serve as the primary inoculum on many hosts. Studies were
      conducted to determine the effect of temperature (5 to 50 degrees C), pH (2 to
      12) and nutrient regimes on microsclerotia germination. The optimal condition for
      microsclerotium germination was 20 degrees C with pH 8.0 whereas nutrient regimes
      had no significant effect on its germination. The whole genome wide expression
      profiles during microsclerotium germination were characterized using the Illumina
      sequencing technology. Approximately 7.4 million of 21-nt cDNA tags were
      sequenced in the cDNA libraries derived from germinated and non-germinated
      microsclerotia. About 3.9% and 2.3% of the unique tags were up-regulated and down
      regulated at least five-fold, respectively, in the germinated microsclerotia
      compared with the non-germinated microsclerotia. A total of 1654 genes showing
      differential expression were identified. Genes that are likely to have played
      important roles in microsclerotium germination include those encoding G-protein
      coupled receptor, lipase/esterase, cyclopentanone 1,2-monooxygenase, H(+)/hexose
      cotransporter 1, fungal Zn(2)-Cys(6) binuclear cluster domain, thymus-specific
      serine protease, glucan 1,3-beta-glucosidase, and alcohol dehydrogenase. These
      genes were mainly up-regulated or down-regulated only in germinated
      microsclerotia, compared with non-germinated microsclerotia. The differential
      expression of genes was confirmed by qRT-PCR analysis of 20 randomly selected
      genes from the 40 most differentially expressed genes. 

PMID- 24927480
TI  - KRAS NF-kappaB is involved in the development of zinc resistance and reduced
      curability in prostate cancer.
AB  - Zinc(II) ions are important components of many proteins and are involved in
      numerous cellular processes such as apoptosis or drug resistance. Prostate cancer
      has a unique relationship with zinc(II) ions. However, the relationship was
      examined only in short-term zinc(II) treatments. Therefore, the aim of this study
      was to create zinc-resistant prostatic cell lines at various stages of the
      disease (22Rv1 and PC-3) and a normal prostate epithelium (PNT1A) using a long
      term zinc exposure. Consequently, the expression profile of the following genes
      was analyzed: BAX, Bcl-2, Beclin-1, CFLAR, HIF1alpha, KRAS, mTOR, MT1A, MT2A, NF
      kappaB1, p53, survivin, ZIP1, ZnT-1. The resistance was verified using the MTT
      test; on average a 1.35-fold lower zinc(II) toxicity (higher IC50) was determined
      in zinc(II)-resistant cells. The associated resistance to cisplatin was also
      determined; IC50 for cisplatin was 1.52-fold higher. With regard to the gene
      expression profiles, our results indicate that differential mechanisms
      participate in the short-term zinc toxicity regulation and long-term resistance;
      the short-term treatment was associated with MT2A (p < 0.001), ZnT-1 (p < 0.001),
      and MT1A (p < 0.03) and the long-term resistance was associated particularly with
      NF-kappaB1 (p < 0.001), CFLAR (p < 0.001), KRAS (p < 0.001), p53 (p < 0.002),
      survivin (p = 0.02), ZIP1 (p = 0.002), BAX (p = 0.005), and HIF1alpha (p = 0.05).
      Therefore, the KRAS-PI3K-NF-kappaB pathway is expected to play a crucial role in
      the regulation of zinc resistance. In summary, compared to previous studies,
      identical mechanisms of resistance were demonstrated on multiple cell lines, both
      non-tumor and tumorous, derived both from primary and advanced secondary sites.

PMID- 24927482
TI  - The efficacy of subcostal-approach laparoscopic cholecystectomy in patients with
      previous midline incisions: comparative analysis with conventional laparoscopic
      cholecystectomy.
AB  - BACKGROUND: In patients with previous abdominal surgery, difficulties in
      laparoscopic cholecystectomy (LC) are associated with adhesions from the previous
      surgery. We reported the efficacy of a subcostal-approach LC (SALC) in patients
      with previous midline incisions. SUBJECTS AND METHODS: Thirty-five patients with
      previous upper midline incision who underwent SALC from 2009 to 2013 at Korea
      University Medical Center (Seoul, Korea) were included. In SALC, a subcostal
      incision instead of an umbilical one was used to avoid adhesion in the midline
      scar. We compared the clinical outcomes of SALC with those of conventional LC in
      patients with previous midline incisions. RESULTS: In the SALC group, there were
      25 men and 10 women. The mean age was 64 years. Median operative time was 60
      minutes, and the median length of postoperative hospital stay was 2 days. Most of
      the patients underwent three-port cholecystectomy. Three patients underwent
      conversion to open surgery. The SALC group had a significantly shorter
      postoperative hospital stay and shorter operation time compared with the
      conventional LC (with supraumbilical incision) group. CONCLUSIONS: SALC is a safe
      and effective procedure for patients who have had a previous midline incision
      that can help prevent unnecessary adhesiolysis.

PMID- 24927483
TI  - N,N'-Bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine based d(10)
      transition metal complexes and their utilization in co-sensitized solar cells.
AB  - N,N'-Bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine based four
      coordinated d(10) transition metal complexes (named ML, M = Zn, Cd, Hg) were
      synthesized and employed as co-sensitizers and co-adsorbents in combination with
      a ruthenium complex N719 in dye sensitized solar cells. After co-sensitization,
      not only the incident-photon-to-current conversion efficiency is enhanced but
      also the dark current is reduced. A short circuit current density of 14.46 mA cm(
      2), an open circuit voltage of 0.74 V and a fill factor of 0.62 corresponding to
      an overall conversion efficiency of 6.65% under AM 1.5 G solar irradiation were
      achieved when ZnL was used as a co-sensitizer, which are much higher than that
      for DSSCs only sensitized by N719 (5.22%) under the same conditions. The
      improvement in efficiency is attributed to the fact that N,N'-bis((6
      methoxylpyridin-2-yl)methylene)-p-phenylenediimine coordinated complexes overcome
      the deficiency of N719 absorption in the low wavelength region of the visible
      spectrum, prevent its aggregation, offset competitive visible light absorption of
      I3(-) and reduce charge recombination due to formation of an effective cover
      layer of the dye molecules on the TiO2 surface. As a result, the synthesized
      complexes are promising candidates as co-adsorbents and co-sensitizers for highly
      efficient DSSCs. 

PMID- 24927484
TI  - Size-controlled nanoparticle-guided assembly of block copolymers for convex lens
      shaped particles.
AB  - The tuning of interfacial properties at selective and desired locations on the
      particles is of great importance to create the novel structured particles by
      breaking the symmetry of their surface property. Herein, a dramatic transition of
      both the external shape and internal morphology of the particles of polystyrene-b
      poly(4-vinylpyridine) (PS-b-P4VP) was induced by precise positioning of size
      controlled Au nanoparticle surfactants (Au NPs). The size-dependent assembly of
      the Au NPs was localized preferentially at the interface between the P4VP domain
      at the particle surface and the surrounding water, which generated a balanced
      interfacial interaction between two different PS/P4VP domains of the BCP
      particles and water, producing unique convex lens-shaped BCP particles. In
      addition, the neutralized interfacial interaction, in combination with the
      directionality of the solvent-induced ordering of the BCP domains from the
      interface of the particle/water, generated defect-free, vertically ordered porous
      channels within the particles. The mechanism for the formation of these novel
      nanostructures was investigated systemically by varying the size and the volume
      fraction of the Au NPs. Furthermore, these convex lens-shaped particles with
      highly ordered channels can be used as a microlens, in which the light can be
      concentrated toward the focal point with enhanced near-field signals. And, these
      particles can possess additional optical properties such as unique distribution
      of light scattering as a result of the well-ordered Au cylinders that filled into
      the channels, which hold great promise for use in optical, biological-sensing,
      and imaging applications. 

PMID- 24927485
TI  - In situ study of oxidative etching of palladium nanocrystals by liquid cell
      electron microscopy.
AB  - Oxidative etching has widely prevailed in the synthesis of a crystal and played a
      critical role in determining the final growth behavior. In this Letter, we report
      an in situ microscopic study on the oxidative etching of palladium cubic
      nanocrystals by liquid cell scanning transmission electron microscopy. The
      etching was realized with oxidative radiation reactants from electron-water
      interaction in the presence of Br(-) ions. Dissolution dynamics of monodispersed
      and aggregated nanocrystals were both investigated and compared. Analyses on the
      dissolution kinetics of nanocrystals and the diffusion kinetics of the dissolved
      agents were carried out based on the scanning transmission electron microscopy
      characterizations. The results presented here pave a way toward the quantitative
      understanding of the oxidative etching reaction and its application in the
      functionally orientated fabrication of nanocrystals with certain sizes,
      structures, and morphologies. 

PMID- 24927486
TI  - Hybrid bio-organic interfaces with matchable nanoscale topography for durable
      high extracellular electron transfer activity.
AB  - Here, we developed a novel hybrid bio-organic interface with matchable nano-scale
      topography between a polypyrrole nanowire array (PPy-NA) and the bacterium
      Shewanella, which enabled a remarkably increased extracellular electron transfer
      (EET) current from genus Shewanella over a rather long period. PPy-NA thus
      exhibited outstanding performance in mediating bacterial EET, which was superior
      to normal electrodes such as carbon plates, Au and tin-doped In2O3. It was
      proposed that the combined effect of the inherent electrochemical nature of PPy
      and the porous structured bacterial network that was generated on the PPy-NA
      enabled long-term stability, while the high efficiency was attributed to the
      enhanced electron transfer rate between PPy-NA and microbes caused by the
      enhanced local topological interactions.

PMID- 24927487
TI  - Inhibitory effects of Picrasma quassioides (D.Don) Benn. on airway inflammation
      in a murine model of allergic asthma.
AB  - Picrasma quassioides (D.Don) Benn. (PQ) is used in traditional medicine for the
      treatment of inflammatory conditions, including gastritis. This study aimed to
      evaluate the inhibitory effects of PQ on the inflammatory responses in mice with
      allergic asthma induced by ovalbumin (OVA) and in lipopolysaccharide (LPS)
      stimulated RAW264.7 cells. To induce allergic asthma, the mice underwent OVA
      sensitization on days 0 and 14 and then were challenged with OVA from days 21-23.
      The mice were administered 15 and 30 mg/kg doses of PQ 1 h prior to the OVA
      challenge. The PQ treatment decreased the inflammatory cell count in the
      bronchoalveolar lavage fluid of the mice and reduced the levels of interleukin
      (IL)-4, IL-5, IL-13 and immunoglobulin (Ig)E when compared with those in the OVA
      group. The PQ treatment also reduced the airway hyperresponsiveness induced by
      the OVA challenge, attenuated the recruitment of inflammatory cells and the mucus
      production in the airways of the mice. In the LPS-stimulated RAW264.7 cells, the
      PQ treatment reduced the overexpression of inducible nitric oxide synthase
      (iNOS). The results indicated that PQ inhibits inflammatory responses in mice
      with OVA-sensitized/challenged allergic asthma and in LPS-stimulated RAW264.7
      cells. These effects were considered to be associated with the suppression of
      iNOS expression. Therefore, PQ may have the potential to treat airway
      inflammatory diseases, including allergic asthma.

PMID- 24927488
TI  - Associations between gender, coping patterns and functioning for individuals with
      chronic pain: a systematic review.
AB  - BACKGROUND: Developing strategies for coping with chronic pain is an integral
      part of successfully living with this often debilitating health condition. While
      gender differences in pain coping strategies have long been investigated, the
      relationship between gender-specific engagement in coping and associated
      functioning in individuals experiencing chronic pain is yet to be clearly
      understood. OBJECTIVE: The present systematic review focused on studies that
      address these relationships to critically evaluate the available evidence.
      METHODS: A systematic search was conducted using MEDLINE via Ovid, EMBASE,
      PsycINFO and CINAHL, with 7247 titles retrieved. To be included, studies had to
      be in English, focus on adult participants, consider chronic nonmalignant pain,
      use measures of coping and functioning (or disability), report on gender-specific
      outcomes (for coping and functioning [or disability]), and investigate a
      relationship among gender, coping and functioning. One researcher screened
      abstracts and full-text articles, and extracted and tabulated data, while two
      researchers independently assessed potential articles for eligibility and
      methodological quality. RESULTS: Only seven studies met the inclusion criteria -
      six of high quality and one of moderate quality. The presented findings suggest
      that women in pain are more likely to use coping strategies considered to be
      maladaptive, resulting in poorer functioning, while men tend to engage in coping
      strategies considered to be adaptive, leading to better functional outcomes.
      CONCLUSIONS: While there is some evidence supporting gender-specific engagement
      in coping and associated functioning, future research is necessary to expand
      understanding of these interrelations.

PMID- 24927491
TI  - IL-17A concentration of seminal plasma and follicular fluid in infertile men and
      women with various clinical diagnoses.
AB  - Seminal plasma and follicular fluid (FF) cytokine analysis are valuable tools for
      diagnoses and validation of therapeutic approaches for improving the chance of
      conception. Despite the initial discovery over a decade ago, the IL-17 family has
      not received much attention in the case of infertility. In this study, we
      analyzed the level of IL-17A in seminal plasma, follicular fluid and blood serum
      of infertile patients with different clinical diagnoses by Enzyme Linked
      Immunosorbent Assay (ELISA). The results showed that the level of IL-17A was
      higher in seminal plasma and blood serum of varicocele patients than the control
      group. The level of this cytokine was higher in follicular fluid of
      endometriosis, polycystic ovary syndrome (PCOS) and tubal factor patients than
      the control group. A similar elevation in IL-17A level was observed in blood
      serum of these patients. Furthermore, there was a correlation between the numbers
      of meiosis I (MI) oocytes and the level of blood serum and follicular fluid IL
      17A in PCOS patients. Our data suggest a putative role of IL-17A in mediating
      these conditions and may have possible applications in the development of more
      effective diagnostic tools and therapeutic treatments for human reproductive
      disorders. 

PMID- 24927490
TI  - Axon guidance and injury-lessons from Wnts and Wnt signaling.
AB  - Many studies in the past decade have revealed the role and mechanisms of Wnt
      signaling in axon guidance during development and the reinduction of Wnt
      signaling in adult central nervous system axons upon traumatic injury, which has
      profound influences on axon regeneration. With 19 Wnts and 14 known receptors (10
      Frizzleds (Fzds), Ryk, Ror1/2 and PTK7), the Wnt family signaling proteins
      contribute significantly to the wiring specificity of the complex brain and
      spinal cord circuitry. Subsequent investigation into the signaling mechanisms
      showed that conserved cell polarity pathways mediate growth cone steering. These
      cell polarity pathways may unveil general principles of growth cone guidance. The
      reappeared Wnt signaling system after spinal cord injury limits the regrowth of
      both descending and ascending motor and sensory axons. Therefore, the knowledge
      of Wnt signaling mechanisms learned from axon development can be applied to axon
      repair in adulthood. 

PMID- 24927492
TI  - Isolation and structure elucidation of cystargamide, a lipopeptide from
      Kitasatospora cystarginea.
AB  - A new lipopeptide, cystargamide (1) was isolated from the fermentation broth of
      the actinomycete Kitasatospora cystarginea. The bacterial strain was selected
      from a set of 12 Kitasatospora spp. using a secondary metabolomics approach
      combining liquid chromatography/high-resolution mass spectrometry (LC-HRMS) with
      principal component analysis (PCA). Cystargamide (1) was purified by reversed
      phase HPLC, and the structure elucidation was achieved by interpreting mass
      spectrometry and NMR data. Cystargamide (1) contains rare structural features
      including a 5-hydroxy tryptophan residue and a 2,3-epoxydecanoyl fatty acid
      group. 

PMID- 24927493
TI  - Effect of the piperazine unit and metal-binding site position on the solubility
      and anti-proliferative activity of ruthenium(II)- and osmium(II)- arene complexes
      of isomeric indolo[3,2-c]quinoline-piperazine hybrids.
AB  - In this study, the indoloquinoline backbone and piperazine were combined to
      prepare indoloquinoline-piperazine hybrids and their ruthenium- and osmium-arene
      complexes in an effort to generate novel antitumor agents with improved aqueous
      solubility. In addition, the position of the metal-binding unit was varied, and
      the effect of these structural alterations on the aqueous solubility and
      antiproliferative activity of their ruthenium- and osmium-arene complexes was
      studied. The indoloquinoline-piperazine hybrids L(1-3) were prepared in situ and
      isolated as six ruthenium and osmium complexes [(eta(6)-p-cymene)M(L(1-3))Cl]Cl,
      where L(1) = 6-(4-methylpiperazin-1-yl)-N-(pyridin-2-yl-methylene)-11H-indolo[3,2
      c]quinolin-2-N-amine, M = Ru ([1a]Cl), Os ([1b]Cl), L(2) = 6-(4-methylpiperazin-1
      yl)-N-(pyridin-2-yl-methylene)-11H-indolo[3,2-c]quinolin-4-N-amine, M = Ru
      ([2a]Cl), Os ([2b]Cl), L(3) = 6-(4-methylpiperazin-1-yl)-N-(pyridin-2-yl
      methylene)-11H-indolo[3,2-c]quinolin-8-N-amine, M = Ru ([3a]Cl), Os ([3b]Cl). The
      compounds were characterized by elemental analysis, one- and two-dimensional NMR
      spectroscopy, ESI mass spectrometry, IR and UV-vis spectroscopy, and single
      crystal X-ray diffraction. The antiproliferative activity of the isomeric
      ruthenium and osmium complexes [1a,b]Cl-[3a,b]Cl was examined in vitro and showed
      the importance of the position of the metal-binding site for their cytotoxicity.
      Those complexes containing the metal-binding site located at the position 4 of
      the indoloquinoline scaffold ([2a]Cl and [2b]Cl) demonstrated the most potent
      antiproliferative activity. The results provide important insight into the
      structure-activity relationships of ruthenium- and osmium-arene complexes with
      indoloquinoline-piperazine hybrid ligands. These studies can be further utilized
      for the design and development of more potent chemotherapeutic agents. 

PMID- 24927495
TI  - Progress in the synthesis and transformations of alkylidenecyclopropanes and
      alkylidenecyclobutanes.

PMID- 24927494
TI  - HIV-positive men's experiences with integrated family planning and HIV services
      in western Kenya: integration fosters male involvement.
AB  - A growing body of evidence indicates that integrating family planning (FP)
      services into HIV care is effective at improving contraceptive uptake among HIV
      positive women in resource-poor settings, yet little research has examined HIV
      positive men's experiences with such integration. We conducted in-depth
      interviews with 21 HIV-positive men seeking care at HIV clinics in Nyanza, Kenya.
      All clinics were intervention sites for a FP/HIV service integration cluster
      randomized trial. Grounded theory was used to code and analyze the data. Our
      findings highlight men's motivations for FP, reasons why men prefer obtaining
      their FP services, which include education, counseling, and commodities, at HIV
      care clinics, and specific ways in which integrated FP/HIV services fostered male
      inclusion in FP decision-making. In conclusion, men appear invested in FP and
      their inclusion in FP decision-making may bolster both female and male agency.
      Men's positive attitudes towards FP being provided at HIV care clinics supports
      the programmatic push towards integrated delivery models for FP and HIV services.

PMID- 24927496
TI  - Chemiexcitation induced proton transfer: enolate oxyluciferin as the firefly
      bioluminophore.
AB  - Firefly bioluminescence is a phenomenon that attracts attention from the research
      community because of complex challenges for fundamental investigation, as well as
      diverse opportunities for practical application. Here we have studied the
      potential deprotonation of firefly oxyluciferin by using a theoretical approach
      in an enzymatic-like microenvironment in chemiexcited proton transfer involving
      adenosine 5'-monophosphate. We have uncovered a reaction route that links the
      evidence that the light-emitter is an anionic molecule while it is chemiexcited
      in its neutral form. Moreover, the results indicated that the anionic
      bioluminophore is the enolate anion and not the ketonic one. Further calculations
      supported this identification of the light-emitter: the spectrum of resulting
      enolate anion covers the entire yellow-green/red bioluminescence range, which is
      in line with the experimental findings regarding firefly multicolor
      bioluminescence. 

PMID- 24927497
TI  - Narrative Focus Predicts Symptom Change Trajectories in Group Treatment for
      Traumatized and Bereaved Adolescents.
AB  - Growing evidence supports the effectiveness of Trauma and Grief Component Therapy
      for Adolescents (TGCT-A) in reducing posttraumatic stress disorder (PTSD)
      symptoms and maladaptive grief (MG) reactions. This pilot study explored whether
      the specific focus of students' narratives (i.e., focus on trauma vs. focus on
      loss) as shared by TGCT-A group members would predict initial pretreatment
      levels, as well as pre- to posttreatment change trajectories, of PTSD symptoms
      and MG reactions. Thirty-three adolescents from three middle schools completed a
      17-week course of group-based TGCT-A. PTSD and MG symptoms were assessed at
      pretreatment, twice during treatment, and at posttreatment. The focus (trauma vs.
      loss) of each student's narrative was coded using transcripts of members'
      narratives as shared within the groups. The reliable change index showed that 61%
      of students reported reliable pre-post improvement in either PTSD symptoms or MG
      reactions. Students whose narratives focused on loss both reported higher
      starting levels and showed steeper rates of decline in MG reactions than students
      whose narratives focused on trauma. In contrast, students whose narratives
      focused on trauma reported higher starting levels of PTSD than students who
      narrated loss experiences. However, narrative focus was not significantly linked
      to the rate at which PTSD symptoms declined over the course of treatment. This
      study provides preliminary evidence that TGCT-A treatment components are
      associated with reduced PTSD symptoms and MG reactions. Loss-focused narratives,
      in particular, appear to be associated with greater decreases in MG reactions. 

PMID- 24927498
TI  - Effect of mobile telephones on sperm quality: a systematic review and meta
      analysis.
AB  - Mobile phones are owned by most of the adult population worldwide. Radio
      frequency electromagnetic radiation (RF-EMR) from these devices could potentially
      affect sperm development and function. Around 14% of couples in high- and middle
      income countries have difficulty conceiving, and there are unexplained declines
      in semen quality reported in several countries. Given the ubiquity of mobile
      phone use, the potential role of this environmental exposure needs to be
      clarified. A systematic review was therefore conducted, followed by meta-analysis
      using random effects models, to determine whether exposure to RF-EMR emitted from
      mobile phones affects human sperm quality. Participants were from fertility
      clinic and research centres. The sperm quality outcome measures were motility,
      viability and concentration, which are the parameters most frequently used in
      clinical settings to assess fertility. We used ten studies in the meta-analysis,
      including 1492 samples. Exposure to mobile phones was associated with reduced
      sperm motility (mean difference -8.1% (95% CI -13.1, -3.2)) and viability (mean
      difference -9.1% (95% CI -18.4, 0.2)), but the effects on concentration were more
      equivocal. The results were consistent across experimental in vitro and
      observational in vivo studies. We conclude that pooled results from in vitro and
      in vivo studies suggest that mobile phone exposure negatively affects sperm
      quality. Further study is required to determine the full clinical implications
      for both sub-fertile men and the general population. 

PMID- 24927499
TI  - Australia's leading public health body delays action on the revision of the
      public health goal for blood lead exposures.
AB  - Globally, childhood blood lead levels have fallen precipitously in developed
      countries since the 1970s following action by international bodies such as the
      WHO and Food and Agricultural Organization (FAO) of the United Nations. These
      reductions have been affected by the activities of national agencies such as the
      US EPA and US Centers for Disease Control and Prevention in the establishment of
      air lead and blood lead standards, the introduction of legislation to remove lead
      from petrol, paint and consumer products and tighter restrictions on lead
      emissions. The outcome of recent major international reviews of research into the
      effects of low-level lead exposures (e.g. by WHO, USA health and environmental
      agencies, German and Canadian health bodies) has resulted in recommendations to
      reduce and eliminate lead exposures. By contrast, Australian policy responses to
      the incontrovertible evidence that adverse neurocognitive and behavioural effects
      that occur at levels well below the current national goal of 10MUg/dL have
      stalled. The delayed response by Australia occurs at a time when blood lead
      levels in two of Australia's three primary lead mining and smelting cities: Port
      Pirie, South Australia and Broken Hill, New South Wales, are rising. In the third
      city, Mount Isa, Queensland, there is still no systematic, annual testing of
      childhood blood lead values. This is despite the fact that Mount Isa has the
      highest lead (and other toxic metals such as cadmium and arsenic) emissions to
      the environment (120tonnes of lead in 2011/12) from any single point source in
      Australia. It is clear that both state and national policy approaches to the
      ongoing risks of lead exposure need to be revised urgently and in line with
      contemporary international standards. Recommended changes should include a new
      lower blood lead intervention level of no more than 5MUg/dL, with a national goal
      for all children under 5years of age to have a blood lead level of below 1MUg/dL
      by 2020. In order to achieve any new lower exposure goals other relevant lead
      standards including air, dust, soil and water must also be revised downwards. 

PMID- 24927500
TI  - Selection and expression profiles of reference genes in mouse preimplantation
      embryos of different ploidies at various developmental stages.
AB  - Real-time reverse transcription quantitative polymerase chain reaction (qPCR) has
      become the most frequently used system for studies of gene expression. Many
      studies have provided reliable evidence that the transcription levels of
      reference genes are not constant at different developmental stages and in
      different experimental conditions. However, suitable reference genes which are
      stably expressed in polyploid preimplantation embryos of different developmental
      stages have not yet been identified. Therefore, it is critical to verify
      candidate reference genes to analyze gene expression accurately in both diploid
      and polyploid embryos. We examined the expression levels of 12 candidate
      reference genes in preimplantation embryos of four different ploidies at six
      developmental stages. Stability analysis of the reference genes was performed by
      four independent software programs, and the stability of three genes was
      evaluated by comparison with the Oct4 expression level during preimplantation
      development in diploid embryos. The expression levels of most genes in the
      polyploid embryos were higher than that in the diploid embryos, but the
      increasing degree were disproportionate with the ploidies. There were no
      significant difference in reference gene expressions among embryos of different
      ploidies when they reached the morula stage, and the expression level remained
      flat until the blastocyst stage. Ubc, Ppia, and Pgk1 were the three most stable
      reference genes in diploid and polyploid embryos.

PMID- 24927501
TI  - C-terminal region of MAP7 domain containing protein 3 (MAP7D3) promotes
      microtubule polymerization by binding at the C-terminal tail of tubulin.
AB  - MAP7 domain containing protein 3 (MAP7D3), a newly identified microtubule
      associated protein, has been shown to promote microtubule assembly and stability.
      Its microtubule binding region has been reported to consist of two coiled coil
      motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus
      and belongs to the microtubule associated protein 7 (MAP7) family. The MAP7
      domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of
      MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of
      MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule
      binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to
      microtubules as well as enhanced the assembly of microtubules in vitro.
      Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD) with
      the C-terminal tail (CT) of the protein promoted microtubule polymerization to a
      greater extent than MD and CT individually. MDCT stabilized microtubules against
      dilution induced disassembly. MDCT bound to reconstituted microtubules with an
      apparent dissociation constant of 3.0 +/- 0.5 uM. An immunostaining experiment
      showed that MDCT localized along the length of the preassembled microtubules.
      Competition experiments with tau indicated that MDCT shares its binding site on
      microtubules with tau. Further, we present evidence indicating that MDCT binds to
      the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa
      cell extract. Here, we report a microtubule binding region in the C-terminal
      region of MAP7D3 that may have a role in regulating microtubule assembly
      dynamics.

PMID- 24927502
TI  - Postoperative recovery of visual function after macula-off rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To determine which factors affect the recovery of visual function in
      macula off rhegmatogenous retinal detachment (RRD). METHODS: In a prospective
      study of forty-five patients with a primary macula-off RRD of 24 hours to 6 weeks
      duration, the height of the macular detachment was determined by ultrasonography.
      At 12 months postoperatively, best corrected visual acuity (BCVA), contrast
      acuity, and color confusion indexes (CCI) were obtained. RESULTS: Macular
      detachment was present for 2-32 (median 7) days before repair. A shorter duration
      of macular detachment was correlated with a better CCI sature (p = 0.0026) and
      lower LogMAR BCVA (better Snellen visual acuity) (p = 0.012). Also, a smaller
      height of macular detachment was correlated with a lower LogMAR BCVA (p =
      0.0034). A younger age and lower pre-operative LogMAR BCVA at presentation were
      both correlated with better postoperative contrast acuity in the total group
      (age: p = 1.7*10(-4) and pre-operative LogMAR BCVA: p = 0.0034). CONCLUSION:
      Functional recovery after macula-off RRD is affected by the duration and the
      height of the macular detachment. Recovery of contrast acuity is also affected by
      age and BCVA at presentation. MEETING PRESENTATION: ARVO annual meeting 2013, May
      7, Seattle, Washington, United States of America. TRIAL REGISTRATION:
      trialregister.nl NTR839.

PMID- 24927503
TI  - Genome-wide binding of MBD2 reveals strong preference for highly methylated loci.
AB  - MBD2 is a subunit of the NuRD complex that is postulated to mediate gene
      repression via recruitment of the complex to methylated DNA. In this study we
      adopted an MBD2 tagging-approach to study its genome wide binding
      characteristics. We show that in vivo MBD2 is mainly recruited to CpG island
      promoters that are highly methylated. Interestingly, MBD2 binds around 1 kb
      downstream of the transcription start site of a subset of ~ 400 CpG island
      promoters that are characterized by the presence of active histone marks, RNA
      polymerase II (Pol2) and low to medium gene expression levels and H3K36me3
      deposition. These tagged-MBD2 binding sites in MCF-7 show increased methylation
      in a cohort of primary breast cancers but not in normal breast samples,
      suggesting a putative role for MBD2 in breast cancer.

PMID- 24927504
TI  - [Use of generic high dose buprenorphine (HDB): about a qualitative survey].
AB  - OBJECTIVE: Analyze the factors of the low use of buprenorphine (HDB) generic in
      France, studying heath care professionals' and patients' attitudes towards this
      substitution. METHODS: A qualitative method based on the realization of semi
      directive conversations was held. 14 health care professionals and 10 patients
      were interviewed. RESULTS: Generic drug of HDB presents undeniable economic
      benefits and galenic advantages. Physicians suggest this generic at first
      prescription or with stabilized patients. The switch princeps/generic is more
      difficult with patients who diverted the product, or when they are accustomed to
      the brand product. Some patients prefer brand product because of its galenics, or
      of the perception of greater efficiency. CONCLUSION: There is a certain distrust
      compared to this generic. It is necessary to properly support the prescription of
      this drug in order to help health care professionals and patients (therapeutic
      education, medical information, creating a climate of trust).

PMID- 24927505
TI  - Better defining target populations for drugs with a view to reimbursement.
AB  - Reimbursement of drugs by public or private insurance systems is increasingly
      problematic, including in supposedly "rich" countries. There is an international
      consensus to consider the benefit of a Health technology assessment to clarify
      decisions on reimbursement by the collectivity, and this includes taking account
      of the target population of the new drug. The authors debate about the urgent
      need of a better quantification of the target population, which must include a
      qualitative description of this target population and a scientific extrapolation
      of the target population, which is certainly the most challenging problem. 

PMID- 24927506
TI  - [mediEVAL: a new evaluating tool for the medication-use system].
AB  - PURPOSES: A new methodology to evaluate the medication-use system based on a risk
      cartography tool, has been developed. This work has been promoted by the
      Observatoire du medicament et des dispositifs medicaux steriles et de
      l'innovation therapeutique (OMEDIT) from Provence-Alpes-Cote d'Azur (PACA)-Corse
      regions. METHODS: This new methodology has been developed with Excel
      (Microsoft((r))) and has led to the mediEVAL tool. It consists in two categories
      of Excel files: evaluating Excel files (1 for each job of the medication-use
      system) and synthesis Excel files which allow to compile a group of evaluating
      files for a defined area (department, hospital...). RESULTS AND CONCLUSION:
      mediEVAL is a new tool to evaluate quality and risk management of the entire
      medication-use system which has to be used by private or public hospitals of PACA
      and Corsica areas in their appropriate medication-use contract. Then, the OMEDIT
      can get data to provide an inventory of fixtures of the PACA-Corse area
      medication-use system situation.

PMID- 24927507
TI  - Lichen associated with metformin.
AB  - We report an exceptional case of bullous lichen induced by metformin in a patient
      with diabetes mellitus. 

PMID- 24927508
TI  - [Adverse drug reactions reporting is helping "non substituable" prescription!].
AB  - In August 2012, general practitioners of Haute- Garonne received a letter from
      Health insurance system, informing that prescriptions could be endorsed by "not
      substituable" after reporting an adverse drug reactions (ADR). Compared to an
      equivalent period before this letter, we observed an increase of ADRs reports for
      generics, mainly concerning gastrointestinal ADR and lack of efficacy. 

PMID- 24927510
TI  - Tunable swelling and rolling of microgel membranes.
AB  - The tunable swelling and rolling of films assembled via layer-by-layer (LbL)
      methods from poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc)
      microgels and poly(ethylenimine) (PEI) have been systematically studied.
      Microgel/PEI films assembled at pH 7.4 display a high degree of in-plane swelling
      at low pH that dramatically increases the film area and drives self-delamination
      from the substrate to form a free-standing film. The degree of film swelling can
      be controlled by the size of microgels used in film fabrication. Taking advantage
      of this feature, self-rolled scrolls can be easily obtained from microgel/PEI
      films prepared from microgels of two different sizes. The rolling direction can
      be controlled by the assembly of different size microgels in different film
      strata, and the final shape of the scrolls can be controlled by scratching the
      desired film edges. The present work contributes to a deeper understanding of
      microgel/PEI film swelling properties and introduces a facile and novel method to
      prepare free-standing films and self-rolled scrolls. 

PMID- 24927511
TI  - An eHealth Intervention for Patients in Rural Areas: Preliminary Findings From a
      Pilot Feasibility Study.
AB  - BACKGROUND: eHealth facilitation of chronic disease management has potential to
      increase engagement and effectiveness and extend access to care in rural areas.
      OBJECTIVE: The objective of this study was to demonstrate the feasibility and
      acceptability of an eHealth system for the management of chronic conditions in a
      rural setting. METHODS: We developed an online management program which
      incorporated content from the Flinders Chronic Condition Management Program
      (Flinders Program) and used an existing software platform (goACT), which is
      accessible by patients and health care workers using either Web-enabled mobile
      phone or Internet, enabling communication between patients and clinicians. We
      analyzed the impact of this eHealth system using qualitative and simple
      quantitative methods. RESULTS: The eHealth system was piloted with 8 recently
      hospitalized patients from rural areas, average age 63 (SD 9) years, each with an
      average of 5 chronic conditions and high level of psychological distress with an
      average K10 score of 32.20 (SD 5.81). Study participants interacted with the
      eHealth system. The average number of logins to the eHealth system by the study
      participants was 26.4 (SD 23.5) over 29 weeks. The login activity was higher
      early in the week. CONCLUSIONS: The pilot demonstrated the feasibility of
      implementing and delivering a chronic disease management program using a Web
      based patient-clinician application. A qualitative analysis revealed burden of
      illness and low levels of information technology literacy as barriers to patient
      engagement.

PMID- 24927512
TI  - Acceptably aware during general anaesthesia: 'dysanaesthesia'--the uncoupling of
      perception from sensory inputs.
AB  - This review makes the case for 'dysanaesthesia', a term encompassing states of
      mind that can arise in the course of anaesthesia during surgery, characterised by
      an uncoupling of sensation and perceptual experience. This is reflected in a
      macroscopic, functional model of anaesthetically-relevant consciousness. Patients
      in this state can be aware of events but in a neutral way, not in pain, sometimes
      personally dissociated from the experiences. This makes events associated with
      surgery peripheral to their whole experience, such that recall is less likely and
      if it exists, makes any spontaneous report of awareness unlikely. This state of
      perception-sensation uncoupling is therefore broadly acceptable (a minimum
      requirement for acceptable anaesthesia) but since it is likely a dose-related
      phenomenon, may also represent a precursor for awareness with adverse recall.
      This hypothesis uniquely explains the often inconsistent responses seen during
      the experimental paradigm of the 'isolated forearm technique', wherein apparently
      anaesthetised patients exhibit a positive motor response to verbal command, but
      no spontaneous movement to surgery. The hypothesis can also explain the
      relatively high incidence of positive response to relatively direct questions for
      recall (e.g., using the Brice questionnaire; ~1:500; the vast majority of these
      being neutral reports) versus the very low incidence of spontaneous reports of
      awareness (~1:15,000; a higher proportion of these being adverse recollections).
      The hypothesis is consistent with relevant notions from philosophical discussions
      of consciousness, and neuroscientific evidence. Dysanaesthesia has important
      implications for research and also for the development of appropriate monitoring.

PMID- 24927513
TI  - Analysis of different European hazelnut (Corylus avellana L.) cultivars:
      authentication, phenotypic features, and phenolic profiles.
AB  - Hazelnuts exhibit functional properties due to their content in fatty acids and
      phenolic compounds that could positively affect human health. The food industry
      requires precise traits for morphological, chemical, and physical kernel features
      so that some cultivars could be more suitable for specific industrial processing.
      In this study, agronomical and morphological features of 29 hazelnut cultivars
      were evaluated and a detailed structural characterization of kernel polyphenols
      was performed, confirming the presence of protocatechuic acid, flavan-3-ols such
      as catechin, procyanidin B2, six procyanidin oligomers, flavonols, and one
      dihydrochalcone in all the analyzed cultivars. In addition, an innovative
      methodology based on the MALDI-TOF mass spectrometric analysis of peptide/protein
      components extracted from kernels was developed for the authentication of the
      most valuable cultivars. The proposed method is rapid, simple, and reliable and
      holds the potential to be applied in quality control processes. These results
      could be useful in hazelnut cultivar evaluation and choice for growers, breeders,
      and food industry. 

PMID- 24927514
TI  - Solid state parameters, structure elucidation, High Resolution X-Ray Diffraction
      (HRXRD), phase matching, thermal and impedance analysis on L-Proline
      trichloroacetate (L-PTCA) NLO single crystals.
AB  - Nonlinear optical single crystal of L-Proline trichloroacetate (L-PTCA) was
      successfully grown by Slow Evaporation Solution Technique (SEST). The grown
      crystals were subjected to single crystal X-ray diffraction analysis to confirm
      the structure. From the single crystal XRD data, solid state parameters were
      determined for the grown crystal. The crystalline perfection has been evaluated
      using high resolution X-ray diffractometer. The frequencies of various functional
      groups were identified from FTIR spectral analysis. The percentage of
      transmittance was obtained from UV Visible spectral analysis. TGA-DSC
      measurements indicate the thermal stability of the crystal. The dielectric
      constant, dielectric loss and ac conductivity were measured by the impedance
      analyzer. The DC conductivity was calculated by the cole-cole plot method.

PMID- 24927515
TI  - Social support and mastery influence the association between stress and poor
      physical health in parents caring for children with developmental disabilities.
AB  - To date, much of the research linking the stress of caring for children with
      developmental disabilities (e.g. Autism & Down syndrome) with parental health
      outcomes have tended to concentrate on mental health with less attention paid to
      the physical health consequences. Thus, this study sought to explore the
      psychosocial predictors of poor physical health in these caring parents. One
      hundred and sixty-seven parents (109 caregivers and 58 control parents) completed
      measures of stress, child problem behaviours, social support, mastery and
      physical health. Parents of children with developmental disabilities had poorer
      physical health compared to control parents. Stress and mastery, but not social
      support and problem behaviours, were significant predictors of poor physical
      health within caring parents for children with developmental disabilities.
      However, the association between mastery and physical health was mediated by
      perceived stress such that those parents who were higher on mastery reported less
      stress and better physical health; furthermore, the association between stress
      and physical health was moderated by social support; those parents high on social
      support and low in stress had better physical health. These results indicate that
      the paths between psychosocial factors and poor physical health in the caring
      parents are working synergistically rather than in isolation. They also
      underscore the importance of providing multi-component interventions that offer a
      variety of psychosocial resources to meet the precise needs of the parents. 

PMID- 24927516
TI  - Differences in the intellectual profile of children with intellectual vs.
      learning disability.
AB  - The WISC-IV was used to compare the intellectual profile of two groups of
      children, one with specific learning disorders (SLDs), the other with
      intellectual disabilities (ID), with a view to identifying which of the four main
      factor indexes and two additional indexes can distinguish between the groups. We
      collected information on WISC-IV scores for 267 children (Mage=10.61 [SD=2.51],
      range 6-16 years, females=99) with a diagnosis of either SLD or ID. Children with
      SLD performed better than those with ID in all measures. Only the SLD children,
      not the ID children, revealed significant differences in the four main factor
      indexes, and their scores for the additional General Ability Index (GAI) were
      higher than for the Cognitive Proficiency Index (CPI). Children with a diagnosis
      of SLD whose Full-Scale Intelligence Quotient (FSIQ) was <85 showed a similar
      pattern. Our findings confirm the hypothesis that children with SLD generally
      obtain high GAI scores, but have specific deficiencies relating to working memory
      and processing speed, whereas children with ID have a general intellectual
      impairment. These findings have important diagnostic and clinical implications
      and should be considered when making diagnostic decisions in borderline cognitive
      cases.

PMID- 24927517
TI  - Examining related influential factors for dental calculus scaling utilization
      among people with disabilities in Taiwan, a nationwide population-based study.
AB  - Limited studies with large samples have been conducted on the utilization of
      dental calculus scaling among people with physical or mental disabilities. This
      study aimed to investigate the utilization of dental calculus scaling among the
      national disabled population. This study analyzed the utilization of dental
      calculus scaling among the disabled people, using the nationwide data between
      2006 and 2008. Descriptive analysis and logistic regression were performed to
      analyze related influential factors for dental calculus scaling utilization. The
      dental calculus scaling utilization rate among people with physical or mental
      disabilities was 16.39%, and the annual utilization frequency was 0.2 times.
      Utilization rate was higher among the female and non-aboriginal samples.
      Utilization rate decreased with increased age and disability severity while
      utilization rate increased with income, education level, urbanization of
      residential area and number of chronic illnesses. Related influential factors for
      dental calculus scaling utilization rate were gender, age, ethnicity (aboriginal
      or non-aboriginal), education level, urbanization of residence area, income,
      catastrophic illnesses, chronic illnesses, disability types, and disability
      severity significantly influenced the dental calculus scaling utilization rate. 

PMID- 24927518
TI  - Using tablet assisted Social StoriesTM to improve classroom behavior for
      adolescents with intellectual disabilities.
AB  - The present study examined the use of tablet assisted Social StoriesTM
      intervention for three high school students with severe intellectual disabilities
      whose problem behavior interfered with their learning and caused classroom
      disruptions. A multiple probe design across participants was employed to test the
      impact of the tablet assisted SS on the participants' target behaviors. During
      intervention, the participants read the Social Stories that were created on Prezi
      and accessed via Quick Response (QR) codes using a Galaxy Tap smart tablet before
      participating in an academic period. Data indicated that the SS intervention
      decreased disruptive behavior and increased academic engagement in all three
      participants. All three demonstrated generalization of behaviors to a nontargeted
      academic period and maintenance of improved behaviors at the 2-week follow-up. 

PMID- 24927519
TI  - Sculpting the apples of science.

PMID- 24927521
TI  - Inner workings: Spraying to see cancer cells.

PMID- 24927523
TI  - TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion
      and hepatic lipid droplet content.
AB  - Genome-wide association studies have identified a locus on chromosome 19
      associated with plasma triglyceride (TG) concentration and nonalcoholic fatty
      liver disease. However, the identity and functional role of the gene(s)
      responsible for these associations remain unknown. Of 19 expressed genes
      contained in this locus, none has previously been implicated in lipid metabolism.
      We performed gene expression studies and expression quantitative trait locus
      analysis in 206 human liver samples to identify the putative causal gene.
      Transmembrane 6 superfamily member 2 (TM6SF2), a gene with hitherto unknown
      function, expressed predominantly in liver and intestine, was identified as the
      putative causal gene. TM6SF2 encodes a protein of 351 amino acids with 7-10
      predicted transmembrane domains. Otherwise, no other protein features were
      identified which could help to elucidate the function of TM6SF2. Protein
      subcellular localization studies with confocal microscopy demonstrated that
      TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate
      compartment of human liver cells. Functional studies for secretion of TG-rich
      lipoproteins (TRLs) and lipid droplet content were performed in human hepatoma
      Huh7 and HepG2 cells using confocal microscopy and siRNA inhibition and
      overexpression techniques. In agreement with the genome-wide association data, it
      was found that TM6SF2 siRNA inhibition was associated with reduced secretion of
      TRLs and increased cellular TG concentration and lipid droplet content, whereas
      TM6SF2 overexpression reduced liver cell steatosis. We conclude that TM6SF2 is a
      regulator of liver fat metabolism with opposing effects on the secretion of TRLs
      and hepatic lipid droplet content. 

PMID- 24927525
TI  - Antigen expression level threshold tunes the fate of CD8 T cells during primary
      hepatic immune responses.
AB  - CD8 T-cell responses to liver-expressed antigens range from deletional tolerance
      to full effector differentiation resulting in overt hepatotoxicity. The reasons
      for these heterogeneous outcomes are not well understood. To identify factors
      that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we
      exploited recombinant adenoassociated viral vectors that enabled us to vary
      potential parameters determining these outcomes in vivo. Our findings reveal a
      threshold of antigen expression within the liver as the dominant factor
      determining T-cell fate, irrespective of T-cell receptor affinity or antigen
      cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate
      antigen, high-affinity T cells developed and maintained effector function,
      whereas, at a high percentage, they became functionally exhausted and silenced.
      Exhaustion was not irreversibly determined by initial activation, but was
      maintained by high intrahepatic antigen load during the early phase of the
      response; cytolytic function was restored when T cells primed under high antigen
      load conditions were transferred into an environment of low-level antigen
      expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T
      cells during hepatic immune responses, and provides an explanation for the
      different immune outcomes observed in a variety of immune-mediated liver
      pathologic conditions. 

PMID- 24927526
TI  - Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning
      and memory in a transgenic mouse model.
AB  - The role of the nuclear receptor TLX in hippocampal neurogenesis and cognition
      has just begun to be explored. In this study, we generated a transgenic mouse
      model that expresses TLX under the control of the promoter of nestin, a neural
      precursor marker. Transgenic TLX expression led to mice with enlarged brains with
      an elongated hippocampal dentate gyrus and increased numbers of newborn neurons.
      Specific expression of TLX in adult hippocampal dentate gyrus via lentiviral
      transduction increased the numbers of BrdU(+) cells and BrdU(+)NeuN(+) neurons.
      Furthermore, the neural precursor-specific expression of the TLX transgene
      substantially rescued the neurogenic defects of TLX-null mice. Consistent with
      increased neurogenesis in the hippocampus, the TLX transgenic mice exhibited
      enhanced cognition with increased learning and memory. These results suggest a
      strong association between hippocampal neurogenesis and cognition, as well as
      significant contributions of TLX to hippocampal neurogenesis, learning, and
      memory. 

PMID- 24927527
TI  - Human memory T cells from the bone marrow are resting and maintain long-lasting
      systemic memory.
AB  - In the bone marrow, a population of memory T cells has been described that
      promotes efficient secondary immune responses and has been considered to be
      preactivated, owing to its expression of CD69 and CD25. Here we show that human
      bone marrow professional memory T cells are not activated but are resting in
      terms of proliferation, transcription, and mobility. They are in the G0 phase of
      the cell cycle, and their transcriptome is that of resting T cells. The
      repertoire of CD4(+) bone marrow memory T cells compared with CD4(+) memory T
      cells from the blood is significantly enriched for T cells specific for
      cytomegalovirus-pp65 (immunodominant protein), tetanus toxoid, measles, mumps,
      and rubella. It is not enriched for vaccinia virus and Candida albicans-MP65
      (immunodominant protein), typical pathogens of skin and/or mucosa. CD4(+) memory
      T cells specific for measles are maintained nearly exclusively in the bone
      marrow. Thus, CD4(+) memory T cells from the bone marrow provide long-term memory
      for systemic pathogens. 

PMID- 24927528
TI  - Pituitary tumor-transforming gene 1 regulates the patterning of retinal mosaics.
AB  - Neurons are commonly organized as regular arrays within a structure, and their
      patterning is achieved by minimizing the proximity between like-type cells, but
      molecular mechanisms regulating this process have, until recently, been
      unexplored. We performed a forward genetic screen using recombinant inbred (RI)
      strains derived from two parental A/J and C57BL/6J mouse strains to identify
      genomic loci controlling spacing of cholinergic amacrine cells, which is a
      subclass of retinal interneuron. We found conspicuous variation in mosaic
      regularity across these strains and mapped a sizeable proportion of that
      variation to a locus on chromosome 11 that was subsequently validated with a
      chromosome substitution strain. Using a bioinformatics approach to narrow the
      list of potential candidate genes, we identified pituitary tumor-transforming
      gene 1 (Pttg1) as the most promising. Expression of Pttg1 was significantly
      different between the two parental strains and correlated with mosaic regularity
      across the RI strains. We identified a seven-nucleotide deletion in the Pttg1
      promoter in the C57BL/6J mouse strain and confirmed a direct role for this motif
      in modulating Pttg1 expression. Analysis of Pttg1 KO mice revealed a reduction in
      the mosaic regularity of cholinergic amacrine cells, as well as horizontal cells,
      but not in two other retinal cell types. Together, these results implicate Pttg1
      in the regulation of homotypic spacing between specific types of retinal neurons.
      The genetic variant identified creates a binding motif for the transcriptional
      activator protein 1 complex, which may be instrumental in driving differential
      expression of downstream processes that participate in neuronal spacing. 

PMID- 24927529
TI  - Structural and functional insight into TAF1-TAF7, a subcomplex of transcription
      factor II D.
AB  - Transcription factor II D (TFIID) is a multiprotein complex that nucleates
      formation of the basal transcription machinery. TATA binding protein-associated
      factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the
      regulation of eukaryotic transcription initiation and play key roles in
      preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a
      dissociable inhibitor of TAF1 histone acetyltransferase activity and that this
      event ensures appropriate assembly of the RNA polymerase II-mediated PIC before
      transcriptional initiation. Here, we report the 3D structure of a complex of
      yeast TAF1 with TAF7 at 2.9 A resolution. The structure displays novel
      architecture and is characterized by a large predominantly hydrophobic
      heterodimer interface and extensive cofolding of TAF subunits. There are no
      obvious similarities between TAF1 and known histone acetyltransferases. Instead,
      the surface of the TAF1-TAF7 complex contains two prominent conserved surface
      pockets, one of which binds selectively to an inhibitory trimethylated histone H3
      mark on Lys27 in a manner that is also regulated by phosphorylation at the
      neighboring H3 serine. Our findings could point toward novel roles for the TAF1
      TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks. 

PMID- 24927530
TI  - An evolving autoimmune microenvironment regulates the quality of effector T cell
      restimulation and function.
AB  - Defining the processes of autoimmune attack of tissues is important for
      inhibiting continued tissue destruction. In type 1 diabetes, it is not known how
      cytotoxic effector T cell responses evolve over time in the pancreatic islets
      targeted for destruction. We used two-photon microscopy of live, intact,
      individual islets to investigate how progression of islet infiltration altered
      the behavior of infiltrating islet-specific CD8(+) T cells. During early-islet
      infiltration, T-cell interactions with CD11c(+) antigen-presenting cells (APCs)
      were stable and real-time imaging of T cell receptor (TCR) clustering provided
      evidence of TCR recognition in these stable contacts. Early T cell-APC encounters
      supported production of IFN-gamma by T effectors, and T cells at this stage also
      killed islet APCs. At later stages of infiltration, T-cell motility accelerated,
      and cytokine production was lost despite the presence of higher numbers of
      infiltrating APCs that were able to trigger T-cell signaling in vitro. Using
      timed introduction of effector T cells, we demonstrate that elements of the
      autoimmune-tissue microenvironment control the dynamics of autoantigen
      recognition by T cells and their resulting pathogenic effector functions. 

PMID- 24927532
TI  - Assessing the implications on air pollution of an alternative control-based
      criterion.

PMID- 24927531
TI  - Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits
      predisposition to atrial fibrillation.
AB  - The molecular mechanisms underlying atrial fibrillation, the most common
      sustained cardiac arrhythmia, remain poorly understood. Genome-wide association
      studies uncovered a major atrial fibrillation susceptibility locus on human
      chromosome 4q25 in close proximity to the paired-like homeodomain transcription
      factor 2 (Pitx2) homeobox gene. Pitx2, a target of the left-sided Nodal signaling
      pathway that initiates early in development, represses the sinoatrial node
      program and pacemaker activity on the left side. To address the mechanisms
      underlying this repressive activity, we hypothesized that Pitx2 regulates
      microRNAs (miRs) to repress the sinoatrial node genetic program. MiRs are small
      noncoding RNAs that regulate gene expression posttranscriptionally. Using an
      integrated genomic approach, we discovered that Pitx2 positively regulates miR-17
      92 and miR-106b-25. Intracardiac electrical stimulation revealed that both miR-17
      92 and miR-106b-25 deficient mice exhibit pacing-induced atrial fibrillation.
      Furthermore electrocardiogram telemetry revealed that mice with miR-17-92 cardiac
      specific inactivation develop prolonged PR intervals whereas mice with miR-17-92
      cardiac-specific inactivation and miR-106b-25 heterozygosity develop sinoatrial
      node dysfunction. Both arrhythmias are risk factors for atrial fibrillation in
      humans. Importantly, miR-17-92 and miR-106b-25 directly repress genes, such as
      Shox2 and Tbx3, that are required for sinoatrial node development. Together, to
      our knowledge, these findings provide the first genetic evidence for an miR loss
      of-function that increases atrial fibrillation susceptibility. 

PMID- 24927534
TI  - Condensation and localization of the partitioning protein ParB on the bacterial
      chromosome.
AB  - The ParABS system mediates chromosome segregation and plasmid partitioning in
      many bacteria. As part of the partitioning mechanism, ParB proteins form a
      nucleoprotein complex at parS sites. The biophysical basis underlying ParB-DNA
      complex formation and localization remains elusive. Specifically, it is unclear
      whether ParB spreads in 1D along DNA or assembles into a 3D protein-DNA complex.
      We show that a combination of 1D spreading bonds and a single 3D bridging bond
      between ParB proteins constitutes a minimal model for a condensed ParB-DNA
      complex. This model implies a scaling behavior for ParB-mediated silencing of
      parS-flanking genes, which we confirm to be satisfied by experimental data from
      P1 plasmids. Furthermore, this model is consistent with experiments on the
      effects of DNA roadblocks on ParB localization. Finally, we show experimentally
      that a single parS site is necessary and sufficient for ParB-DNA complex
      formation in vivo. Together with our model, this suggests that ParB binding to
      parS triggers a conformational switch in ParB that overcomes a nucleation
      barrier. Conceptually, the combination of spreading and bridging bonds in our
      model provides a surface tension ensuring the condensation of the ParB-DNA
      complex, with analogies to liquid-like compartments such as nucleoli in
      eukaryotes. 

PMID- 24927535
TI  - An alcohol-sensing site in the calcium- and voltage-gated, large conductance
      potassium (BK) channel.
AB  - Ethanol alters BK (slo1) channel function leading to perturbation of physiology
      and behavior. Site(s) and mechanism(s) of ethanol-BK channel interaction are
      unknown. We demonstrate that ethanol docks onto a water-accessible site that is
      strategically positioned between the slo1 calcium-sensors and gate. Ethanol only
      accesses this site in presence of calcium, the BK channel's physiological
      agonist. Within the site, ethanol hydrogen-bonds with K361. Moreover,
      substitutions that hamper hydrogen bond formation or prevent ethanol from
      accessing K361 abolish alcohol action without altering basal channel function.
      Alcohol interacting site dimensions are approximately 10.7 * 8.6 * 7.1 A,
      accommodating effective (ethanol-heptanol) but not ineffective (octanol, nonanol)
      channel activators. This study presents: (i) to our knowledge, the first
      identification and characterization of an n-alkanol recognition site in a member
      of the voltage-gated TM6 channel superfamily; (ii) structural insights on ethanol
      allosteric interactions with ligand-gated ion channels; and (iii) a first step
      for designing agents that antagonize BK channel-mediated alcohol actions without
      perturbing basal channel function. 

PMID- 24927536
TI  - Targeted inversion and reversion of the blood coagulation factor 8 gene in human
      iPS cells using TALENs.
AB  - Hemophilia A, one of the most common genetic bleeding disorders, is caused by
      various mutations in the blood coagulation factor VIII (F8) gene. Among the
      genotypes that result in hemophilia A, two different types of chromosomal
      inversions that involve a portion of the F8 gene are most frequent, accounting
      for almost half of all severe hemophilia A cases. In this study, we used a
      transcription activator-like effector nuclease (TALEN) pair to invert a 140-kbp
      chromosomal segment that spans the portion of the F8 gene in human induced
      pluripotent stem cells (iPSCs) to create a hemophilia A model cell line. In
      addition, we reverted the inverted segment back to its normal orientation in the
      hemophilia model iPSCs using the same TALEN pair. Importantly, we detected the F8
      mRNA in cells derived from the reverted iPSCs lines, but not in those derived
      from the clones with the inverted segment. Thus, we showed that TALENs can be
      used both for creating disease models associated with chromosomal rearrangements
      in iPSCs and for correcting genetic defects caused by chromosomal inversions.
      This strategy provides an iPSC-based novel therapeutic option for the treatment
      of hemophilia A and other genetic diseases caused by chromosomal inversions. 

PMID- 24927537
TI  - Mycobacterium tuberculosis supports protein tyrosine phosphorylation.
AB  - Reversible protein phosphorylation determines growth and adaptive decisions in
      Mycobacterium tuberculosis (Mtb). At least 11 two-component systems and 11
      Ser/Thr protein kinases (STPKs) mediate phosphorylation on Asp, His, Ser, and
      Thr. In contrast, protein phosphorylation on Tyr has not been described
      previously in Mtb. Here, using a combination of phospho-enrichment and highly
      sensitive mass spectrometry, we show extensive protein Tyr phosphorylation of
      diverse Mtb proteins, including STPKs. Several STPKs function as dual-specificity
      kinases that phosphorylate Tyr in cis and in trans, suggesting that dual
      specificity kinases have a major role in bacterial phospho-signaling. Mutation of
      a phosphotyrosine site of the essential STPK PknB reduces its activity in vitro
      and in live Mtb, indicating that Tyr phosphorylation has a functional role in
      bacterial growth. These data identify a previously unrecognized phosphorylation
      system in a human pathogen that claims ~ 1.4 million lives every year.

PMID- 24927538
TI  - Requirements and limits for life in the context of exoplanets.
AB  - The requirements for life on Earth, its elemental composition, and its
      environmental limits provide a way to assess the habitability of exoplanets.
      Temperature is key both because of its influence on liquid water and because it
      can be directly estimated from orbital and climate models of exoplanetary
      systems. Life can grow and reproduce at temperatures as low as -15  degrees C,
      and as high as 122  degrees C. Studies of life in extreme deserts show that on a
      dry world, even a small amount of rain, fog, snow, and even atmospheric humidity
      can be adequate for photosynthetic production producing a small but detectable
      microbial community. Life is able to use light at levels less than 10(-5) of the
      solar flux at Earth. UV or ionizing radiation can be tolerated by many
      microorganisms at very high levels and is unlikely to be life limiting on an
      exoplanet. Biologically available nitrogen may limit habitability. Levels of O2
      over a few percent on an exoplanet would be consistent with the presence of
      multicellular organisms and high levels of O2 on Earth-like worlds indicate
      oxygenic photosynthesis. Other factors such as pH and salinity are likely to vary
      and not limit life over an entire planet or moon. 

PMID- 24927539
TI  - Marker for type VI secretion system effectors.
AB  - Bacteria use diverse mechanisms to kill, manipulate, and compete with other
      cells. The recently discovered type VI secretion system (T6SS) is widespread in
      bacterial pathogens and used to deliver virulence effector proteins into target
      cells. Using comparative proteomics, we identified two previously unidentified
      T6SS effectors that contained a conserved motif. Bioinformatic analyses revealed
      that this N-terminal motif, named MIX (marker for type six effectors), is found
      in numerous polymorphic bacterial proteins that are primarily located in the T6SS
      genome neighborhood. We demonstrate that several MIX-containing proteins are T6SS
      effectors and that they are not required for T6SS activity. Thus, we propose that
      MIX-containing proteins are T6SS effectors. Our findings allow for the
      identification of numerous uncharacterized T6SS effectors that will undoubtedly
      lead to the discovery of new biological mechanisms. 

PMID- 24927540
TI  - Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common
      occurrence of nonmodular enzymes.
AB  - Nonribosomal peptides and polyketides are a diverse group of natural products
      with complex chemical structures and enormous pharmaceutical potential. They are
      synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide
      synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we
      report the widespread occurrence of NRPS and PKS genetic machinery across the
      three domains of life with the discovery of 3,339 gene clusters from 991
      organisms, by examining a total of 2,699 genomes. These gene clusters display
      extraordinarily diverse organizations, and a total of 1,147 hybrid NRPS/PKS
      clusters were found. Surprisingly, 10% of bacterial gene clusters lacked modular
      organization, and instead catalytic domains were mostly encoded as separate
      proteins. The finding of common occurrence of nonmodular NRPS differs
      substantially from the current classification. Sequence analysis indicates that
      the evolution of NRPS machineries was driven by a combination of common descent
      and horizontal gene transfer. We identified related siderophore NRPS gene
      clusters that encoded modular and nonmodular NRPS enzymes organized in a
      gradient. A higher frequency of the NRPS and PKS gene clusters was detected from
      bacteria compared with archaea or eukarya. They commonly occurred in the phyla of
      Proteobacteria, Actinobacteria, Firmicutes, and Cyanobacteria in bacteria and the
      phylum of Ascomycota in fungi. The majority of these NRPS and PKS gene clusters
      have unknown end products highlighting the power of genome mining in identifying
      novel genetic machinery for the biosynthesis of secondary metabolites. 

PMID- 24927541
TI  - Primary cilia control hedgehog signaling during muscle differentiation and are
      deregulated in rhabdomyosarcoma.
AB  - The primary cilium acts as a cellular antenna, transducing diverse signaling
      pathways, and recent evidence suggests that primary cilia are important in
      development and cancer. However, a role for cilia in normal muscle development
      and rhabdomyosarcoma (RMS) has not been explored. Here we implicate primary cilia
      in proliferation, hedgehog (Hh) signaling, and differentiation of skeletal muscle
      cells. Cilia and Hh signaling are highly dynamic during the differentiation of
      myoblasts. We show that cilia are assembled during the initial stages of myogenic
      differentiation but disappear as cells progress through myogenesis, concomitant
      with the destruction of proteins critical for cilia assembly and shortly after
      the Hh effector, Gli3, leaves the cilium. Importantly, we show that ablation of
      primary cilia strongly suppresses Hh signaling and myogenic differentiation while
      enhancing proliferation. Interestingly, our data further indicate that both cilia
      assembly and Hh signaling are deregulated in RMS, and cilia respond to Hh ligand
      in certain subsets of RMS cells but not others. Together, these findings provide
      evidence for an essential role for both primary cilia assembly and disassembly in
      the control of Hh signaling and early differentiation in muscle cells. We suggest
      that the temporally orchestrated destruction of centrosomal and ciliary proteins
      is a necessary antecedent for removal of the primary cilium and cessation of Hh
      signaling during myogenic differentiation. Additionally, our results further
      stratify RMS populations and highlight cilia assembly and disassembly as
      potential RMS drug targets. 

PMID- 24927542
TI  - DNA double-strand breaks promote methylation of histone H3 on lysine 9 and
      transient formation of repressive chromatin.
AB  - Dynamic changes in histone modification are critical for regulating DNA double
      strand break (DSB) repair. Activation of the Tip60 acetyltransferase by DSBs
      requires interaction of Tip60 with histone H3 methylated on lysine 9 (H3K9me3).
      However, how H3K9 methylation is regulated during DSB repair is not known. Here,
      we demonstrate that a complex containing kap-1, HP1, and the H3K9
      methyltransferase suv39h1 is rapidly loaded onto the chromatin at DSBs. Suv39h1
      methylates H3K9, facilitating loading of additional kap-1/HP1/suv39h1 through
      binding of HP1's chromodomain to the nascent H3K9me3. This process initiates
      cycles of kap-1/HP1/suv39h1 loading and H3K9 methylation that facilitate
      spreading of H3K9me3 and kap-1/HP1/suv39h1 complexes for tens of kilobases away
      from the DSB. These domains of H3K9me3 function to activate the Tip60
      acetyltransferase, allowing Tip60 to acetylate both ataxia telangiectasia-mutated
      (ATM) kinase and histone H4. Consequently, cells lacking suv39h1 display
      defective activation of Tip60 and ATM, decreased DSB repair, and increased
      radiosensitivity. Importantly, activated ATM rapidly phosphorylates kap-1,
      leading to release of the repressive kap-1/HP1/suv39h1 complex from the
      chromatin. ATM activation therefore functions as a negative feedback loop to
      remove repressive suv39h1 complexes at DSBs, which may limit DSB repair.
      Recruitment of kap-1/HP1/suv39h1 to DSBs therefore provides a mechanism for
      transiently increasing the levels of H3K9me3 in open chromatin domains that lack
      H3K9me3 and thereby promoting efficient activation of Tip60 and ATM in these
      regions. Further, transient formation of repressive chromatin may be critical for
      stabilizing the damaged chromatin and for remodeling the chromatin to create an
      efficient template for the DNA repair machinery. 

PMID- 24927543
TI  - Antibody repertoire deep sequencing reveals antigen-independent selection in
      maturing B cells.
AB  - Antibody repertoires are known to be shaped by selection for antigen binding.
      Unexpectedly, we now show that selection also acts on a non-antigen-binding
      antibody region: the heavy-chain variable (VH)-encoded "elbow" between variable
      and constant domains. By sequencing 2.8 million recombined heavy-chain genes from
      immature and mature B-cell subsets in mice, we demonstrate a striking gradient in
      VH gene use as pre-B cells mature into follicular and then into marginal zone B
      cells. Cells whose antibodies use VH genes that encode a more flexible elbow are
      more likely to mature. This effect is distinct from, and exceeds in magnitude,
      previously described maturation-associated changes in heavy-chain complementarity
      determining region 3, a key antigen-binding region, which arise from junctional
      diversity rather than differential VH gene use. Thus, deep sequencing reveals a
      previously unidentified mode of B-cell selection. 

PMID- 24927544
TI  - Abrogation of alpha-synuclein-mediated dopaminergic neurodegeneration in LRRK2
      deficient rats.
AB  - Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause
      late-onset Parkinson disease. Past studies have provided conflicting evidence for
      the protective effects of LRRK2 knockdown in models of Parkinson disease as well
      as other disorders. These discrepancies may be caused by uncertainty in the
      pathobiological mechanisms of LRRK2 action. Previously, we found that LRRK2
      knockdown inhibited proinflammatory responses from cultured microglia cells.
      Here, we report LRRK2 knockout rats as resistant to dopaminergic
      neurodegeneration elicited by intracranial administration of LPS. Such resistance
      to dopaminergic neurodegeneration correlated with reduced proinflammatory myeloid
      cells recruited in the brain. Additionally, adeno-associated virus-mediated
      transduction of human alpha-synuclein also resulted in dopaminergic
      neurodegeneration in wild-type rats. In contrast, LRRK2 knockout animals had no
      significant loss of neurons and had reduced numbers of activated myeloid cells in
      the substantia nigra. Although LRRK2 expression in the wild-type rat midbrain
      remained undetected under nonpathological conditions, LRRK2 became highly
      expressed in inducible nitric oxide synthase (iNOS)-positive myeloid cells in the
      substantia nigra in response to alpha-synuclein overexpression or LPS exposures.
      Our data suggest that knocking down LRRK2 may protect from overt cell loss by
      inhibiting the recruitment of chronically activated proinflammatory myeloid
      cells. These results may provide value in the translation of LRRK2-targeting
      therapeutics to conditions where neuroinflammation may underlie aspects of
      neuronal dysfunction and degeneration. 

PMID- 24927545
TI  - Plant roots use a patterning mechanism to position lateral root branches toward
      available water.
AB  - The architecture of the branched root system of plants is a major determinant of
      vigor. Water availability is known to impact root physiology and growth; however,
      the spatial scale at which this stimulus influences root architecture is poorly
      understood. Here we reveal that differences in the availability of water across
      the circumferential axis of the root create spatial cues that determine the
      position of lateral root branches. We show that roots of several plant species
      can distinguish between a wet surface and air environments and that this also
      impacts the patterning of root hairs, anthocyanins, and aerenchyma in a
      phenomenon we describe as hydropatterning. This environmental response is
      distinct from a touch response and requires available water to induce lateral
      roots along a contacted surface. X-ray microscale computed tomography and 3D
      reconstruction of soil-grown root systems demonstrate that such responses also
      occur under physiologically relevant conditions. Using early-stage lateral root
      markers, we show that hydropatterning acts before the initiation stage and likely
      determines the circumferential position at which lateral root founder cells are
      specified. Hydropatterning is independent of endogenous abscisic acid signaling,
      distinguishing it from a classic water-stress response. Higher water availability
      induces the biosynthesis and transport of the lateral root-inductive signal auxin
      through local regulation of tryptophan aminotransferase of Arabidopsis 1 and PIN
      formed 3, both of which are necessary for normal hydropatterning. Our work
      suggests that water availability is sensed and interpreted at the suborgan level
      and locally patterns a wide variety of developmental processes in the root.

PMID- 24927546
TI  - Evolution of TNF-induced apoptosis reveals 550 My of functional conservation.
AB  - The Precambrian explosion led to the rapid appearance of most major animal phyla
      alive today. It has been argued that the complexity of life has steadily
      increased since that event. Here we challenge this hypothesis through the
      characterization of apoptosis in reef-building corals, representatives of some of
      the earliest animals. Bioinformatic analysis reveals that all of the major
      components of the death receptor pathway are present in coral with high-predicted
      structural conservation with Homo sapiens. The TNF receptor-ligand superfamilies
      (TNFRSF/TNFSF) are central mediators of the death receptor pathway, and the
      predicted proteome of Acropora digitifera contains more putative coral TNFRSF
      members than any organism described thus far, including humans. This high
      abundance of TNFRSF members, as well as the predicted structural conservation of
      other death receptor signaling proteins, led us to wonder what would happen if
      corals were exposed to a member of the human TNFSF (HuTNFalpha). HuTNFalpha was
      found to bind directly to coral cells, increase caspase activity, cause apoptotic
      blebbing and cell death, and finally induce coral bleaching. Next, immortalized
      human T cells (Jurkats) expressing a functional death receptor pathway (WT) and a
      corresponding Fas-associated death domain protein (FADD) KO cell line were
      exposed to a coral TNFSF member (AdTNF1) identified and purified here. AdTNF1
      treatment resulted in significantly higher cell death (P < 0.0001) in WT Jurkats
      compared with the corresponding FADD KO, demonstrating that coral AdTNF1
      activates the H. sapiens death receptor pathway. Taken together, these data show
      remarkable conservation of the TNF-induced apoptotic response representing 550 My
      of functional conservation. 

PMID- 24927547
TI  - Vesiculoviral matrix (M) protein occupies nucleic acid binding site at
      nucleoporin pair (Rae1 * Nup98).
AB  - mRNA export factor 1 (Rae1) and nucleoporin 98 (Nup98) are host cell targets for
      the matrix (M) protein of vesicular stomatitis virus (VSV). How Rae1 functions in
      mRNA export and how M protein targets both Rae1 and Nup98 are not understood at
      the molecular level. To obtain structural insights, we assembled a 1:1:1 complex
      of M*Rae1*Nup98 and established a crystal structure at 3.15-A resolution. We
      found that the M protein contacts the Rae1*Nup98 heterodimer principally by two
      protrusions projecting from the globular domain of M like a finger and thumb.
      Both projections clamp to the side of the beta-propeller of Rae1, with the finger
      also contacting Nup98. The most prominent feature of the finger is highly
      conserved Methionine 51 (Met51) with upstream and downstream acidic residues. The
      complementary surface on Rae1 displays a deep hydrophobic pocket, into which
      Met51 fastens like a bolt, and a groove of basic residues on either side, which
      bond to the acidic residues of the finger. Notably, the M protein competed for in
      vitro binding of various oligonucleotides to Rae1*Nup98. We localized this
      competing activity of M to its finger using a synthetic peptide. Collectively,
      our data suggest that Rae1 serves as a binding protein for the phosphate backbone
      of any nucleic acid and that the finger of M mimics this ligand. In the context
      of mRNA export, we propose that a given mRNA segment, after having been
      deproteinated by helicase, is transiently reproteinated by Nup98-tethered Rae1.
      We suggest that such repetitive cycles provide cytoplasmic stopover sites
      required for ratcheting mRNA across the nuclear pore. 

PMID- 24927548
TI  - Taxodione and arenarone inhibit farnesyl diphosphate synthase by binding to the
      isopentenyl diphosphate site.
AB  - We used in silico methods to screen a library of 1,013 compounds for possible
      binding to the allosteric site in farnesyl diphosphate synthase (FPPS). Two of
      the 50 predicted hits had activity against either human FPPS (HsFPPS) or
      Trypanosoma brucei FPPS (TbFPPS), the most active being the quinone methide
      celastrol (IC50 versus TbFPPS ~ 20 uM). Two rounds of similarity searching and
      activity testing then resulted in three leads that were active against HsFPPS
      with IC50 values in the range of ~ 1-3 uM (as compared with ~ 0.5 uM for the
      bisphosphonate inhibitor, zoledronate). The three leads were the quinone methides
      taxodone and taxodione and the quinone arenarone, compounds with known
      antibacterial and/or antitumor activity. We then obtained X-ray crystal
      structures of HsFPPS with taxodione+zoledronate, arenarone+zoledronate, and
      taxodione alone. In the zoledronate-containing structures, taxodione and
      arenarone bound solely to the homoallylic (isopentenyl diphosphate, IPP) site,
      not to the allosteric site, whereas zoledronate bound via Mg(2+) to the same site
      as seen in other bisphosphonate-containing structures. In the taxodione-alone
      structure, one taxodione bound to the same site as seen in the
      taxodione+zoledronate structure, but the second located to a more surface-exposed
      site. In differential scanning calorimetry experiments, taxodione and arenarone
      broadened the native-to-unfolded thermal transition (Tm), quite different to the
      large increases in DeltaTm seen with biphosphonate inhibitors. The results
      identify new classes of FPPS inhibitors, diterpenoids and sesquiterpenoids, that
      bind to the IPP site and may be of interest as anticancer and antiinfective drug
      leads.

PMID- 24927549
TI  - Plasticity of hydrogen bond networks regulates mechanochemistry of cell adhesion
      complexes.
AB  - Mechanical forces acting on cell adhesion receptor proteins regulate a range of
      cellular functions by formation and rupture of noncovalent interactions with
      ligands. Typically, force decreases the lifetimes of intact complexes ("slip
      bonds"), making the discovery that these lifetimes can also be prolonged ("catch
      bonds") a surprise. We created a microscopic analytic theory by incorporating the
      structures of selectin and integrin receptors into a conceptual framework based
      on the theory of stochastic equations, which quantitatively explains a wide range
      of experimental data (including catch bonds at low forces and slip bonds at high
      forces). Catch bonds arise due to force-induced remodeling of hydrogen bond
      networks, a finding that also accounts for unbinding in structurally unrelated
      integrin-fibronectin and actomyosin complexes. For the selectin family,
      remodeling of hydrogen bond networks drives an allosteric transition resulting in
      the formation of the maximum number of hydrogen bonds determined only by the
      structure of the receptor and independent of the ligand. A similar transition
      allows us to predict the increase in the number of hydrogen bonds in a particular
      allosteric state of alpha5beta1 integrin-fibronectin complex, a conformation
      which is yet to be crystallized. We also make a testable prediction that a single
      point mutation (Tyr51Phe) in the ligand associated with selectin should
      dramatically alter the nature of the catch bond compared with the wild type. Our
      work suggests that nature uses a ductile network of hydrogen bonds to engineer
      function over a broad range of forces. 

PMID- 24927550
TI  - Genetically engineering Synechocystis sp. Pasteur Culture Collection 6803 for the
      sustainable production of the plant secondary metabolite p-coumaric acid.
AB  - p-Coumaric acid is the precursor of phenylpropanoids, which are plant secondary
      metabolites that are beneficial to human health. Tyrosine ammonia lyase catalyzes
      the production of p-coumaric acid from tyrosine. Because of their photosynthetic
      ability and biosynthetic versatility, cyanobacteria are promising candidates for
      the production of certain plant metabolites, including phenylpropanoids. Here, we
      produced p-coumaric acid in a strain of transgenic cyanobacterium Synechocystis
      sp. Pasteur Culture Collection 6803 (hereafter Synechocystis 6803). Whereas a
      strain of Synechocystis 6803 genetically engineered to express sam8, a tyrosine
      ammonia lyase gene from the actinomycete Saccharothrix espanaensis, accumulated
      little or no p-coumaric acid, a strain that both expressed sam8 and lacked
      slr1573, a native hypothetical gene shown here to encode a laccase that oxidizes
      polyphenols, produced ~82.6 mg/L p-coumaric acid, which was readily purified from
      the growth medium. 

PMID- 24927551
TI  - Differential expression of APE1 and APE2 in germinal centers promotes error-prone
      repair and A:T mutations during somatic hypermutation.
AB  - Somatic hypermutation (SHM) of antibody variable region genes is initiated in
      germinal center B cells during an immune response by activation-induced cytidine
      deaminase (AID), which converts cytosines to uracils. During accurate repair in
      nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving
      abasic sites that are incised by AP endonuclease (APE) to create single-strand
      breaks, and the correct nucleotide is reinserted by DNA polymerase beta. During
      SHM, for unknown reasons, repair is error prone. There are two APE homologs in
      mammals and, surprisingly, APE1, in contrast to its high expression in both
      resting and in vitro-activated splenic B cells, is expressed at very low levels
      in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency
      has very little effect on SHM. In contrast, the less efficient homolog, APE2, is
      highly expressed and contributes not only to the frequency of mutations, but also
      to the generation of mutations at A:T base pair (bp), insertions, and deletions.
      In the absence of both UNG and APE2, mutations at A:T bp are dramatically
      reduced. Single-strand breaks generated by APE2 could provide entry points for
      exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known
      association of APE2 with proliferating cell nuclear antigen could recruit
      translesion polymerases to create mutations at AID-induced lesions and also at
      A:T bp. Our data provide new insight into error-prone repair of AID-induced
      lesions, which we propose is facilitated by down-regulation of APE1 and up
      regulation of APE2 expression in germinal center B cells. 

PMID- 24927552
TI  - Oxytocin promotes social bonding in dogs.
AB  - Recent evidence suggests that enduring social bonds have fitness benefits.
      However, very little is known about the neural circuitry and neurochemistry
      underlying the formation and maintenance of stable social bonds outside
      reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the
      hypothalamus in mammals, regulates many complex forms of social behavior and
      cognition in both human and nonhuman animals. Animal research, however, has
      concentrated on monogamous mammals, and it remains unknown whether OT also
      modulates social bonds in nonreproductive contexts. In this study we provide
      behavioral evidence that exogenous OT promotes positive social behaviors in the
      domestic dog toward not only conspecifics but also human partners. Specifically,
      when sprayed with OT, dogs showed higher social orientation and affiliation
      toward their owners and higher affiliation and approach behaviors toward dog
      partners than when sprayed with placebo. Additionally, the exchange of socio
      positive behaviors with dog partners triggered the release of endogenous OT,
      highlighting the involvement of OT in the development of social relationships in
      the domestic dog. These data provide new insight into the mechanisms that
      facilitate the maintenance of close social bonds beyond immediate reproductive
      interest or genetic ties and complement a growing body of evidence that
      identifies OT as one of the neurochemical foundations of sociality in mammalian
      species. 

PMID- 24927553
TI  - Proterozoic oxygen rise linked to shifting balance between seafloor and
      terrestrial weathering.
AB  - A shift toward higher atmospheric oxygen concentration during the late
      Proterozoic has been inferred from multiple indirect proxies and is seen by many
      as a prerequisite for the emergence of complex animal life. However, the
      mechanisms controlling the level of oxygen throughout the Proterozoic and its
      eventual rise remain uncertain. Here we use a simple biogeochemical model to show
      that the balance between long-term carbon removal fluxes via terrestrial silicate
      weathering and ocean crust alteration plays a key role in determining atmospheric
      oxygen concentration. This balance may be shifted by changes in terrestrial
      weatherability or in the generation rate of oceanic crust. As a result, the
      terrestrial chemical weathering flux may be permanently altered--contrasting with
      the conventional view that the global silicate weathering flux must adjust to
      equal the volcanic CO2 degassing flux. Changes in chemical weathering flux in
      turn alter the long-term supply of phosphorus to the ocean, and therefore the
      flux of organic carbon burial, which is the long-term source of atmospheric
      oxygen. Hence we propose that increasing solar luminosity and a decrease in
      seafloor spreading rate over 1,500-500 Ma drove a gradual shift from seafloor
      weathering to terrestrial weathering, and a corresponding steady rise in
      atmospheric oxygen. Furthermore, increased terrestrial weatherability during the
      late Neoproterozoic may explain low temperature, increases in ocean phosphate,
      ocean sulfate, and atmospheric oxygen concentration at this time.

PMID- 24927554
TI  - Cofactor-dependent conformational heterogeneity of GAD65 and its role in
      autoimmunity and neurotransmitter homeostasis.
AB  - The human neuroendocrine enzyme glutamate decarboxylase (GAD) catalyses the
      synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) using
      pyridoxal 5'-phosphate as a cofactor. GAD exists as two isoforms named according
      to their respective molecular weights: GAD65 and GAD67. Although cytosolic GAD67
      is typically saturated with the cofactor (holoGAD67) and constitutively active to
      produce basal levels of GABA, the membrane-associated GAD65 exists mainly as the
      inactive apo form. GAD65, but not GAD67, is a prevalent autoantigen, with
      autoantibodies to GAD65 being detected at high frequency in patients with
      autoimmune (type 1) diabetes and certain other autoimmune disorders. The
      significance of GAD65 autoinactivation into the apo form for regulation of
      neurotransmitter levels and autoantibody reactivity is not understood. We have
      used computational and experimental approaches to decipher the nature of the holo
      -> apo conversion in GAD65 and thus, its mechanism of autoinactivation. Molecular
      dynamics simulations of GAD65 reveal coupling between the C-terminal domain,
      catalytic loop, and pyridoxal 5'-phosphate-binding domain that drives structural
      rearrangement, dimer opening, and autoinactivation, consistent with limited
      proteolysis fragmentation patterns. Together with small-angle X-ray scattering
      and fluorescence spectroscopy data, our findings are consistent with apoGAD65
      existing as an ensemble of conformations. Antibody-binding kinetics suggest a
      mechanism of mutually induced conformational changes, implicating the flexibility
      of apoGAD65 in its autoantigenicity. Although conformational diversity may
      provide a mechanism for cofactor-controlled regulation of neurotransmitter
      biosynthesis, it may also come at a cost of insufficient development of immune
      self-tolerance that favors the production of GAD65 autoantibodies. 

PMID- 24927555
TI  - Medically important differences in snake venom composition are dictated by
      distinct postgenomic mechanisms.
AB  - Variation in venom composition is a ubiquitous phenomenon in snakes and occurs
      both interspecifically and intraspecifically. Venom variation can have severe
      outcomes for snakebite victims by rendering the specific antibodies found in
      antivenoms ineffective against heterologous toxins found in different venoms. The
      rapid evolutionary expansion of different toxin-encoding gene families in
      different snake lineages is widely perceived as the main cause of venom
      variation. However, this view is simplistic and disregards the understudied
      influence that processes acting on gene transcription and translation may have on
      the production of the venom proteome. Here, we assess the venom composition of
      six related viperid snakes and compare interspecific changes in the number of
      toxin genes, their transcription in the venom gland, and their translation into
      proteins secreted in venom. Our results reveal that multiple levels of regulation
      are responsible for generating variation in venom composition between related
      snake species. We demonstrate that differential levels of toxin transcription,
      translation, and their posttranslational modification have a substantial impact
      upon the resulting venom protein mixture. Notably, these processes act to varying
      extents on different toxin paralogs found in different snakes and are therefore
      likely to be as important as ancestral gene duplication events for generating
      compositionally distinct venom proteomes. Our results suggest that these
      processes may also contribute to altering the toxicity of snake venoms, and we
      demonstrate how this variability can undermine the treatment of a neglected
      tropical disease, snakebite.

PMID- 24927556
TI  - Origins of caprine herding.

PMID- 24927557
TI  - How season and serotype determine dengue transmissibility.

PMID- 24927558
TI  - Recovery of consciousness is mediated by a network of discrete metastable
      activity states.
AB  - It is not clear how, after a large perturbation, the brain explores the vast
      space of potential neuronal activity states to recover those compatible with
      consciousness. Here, we analyze recovery from pharmacologically induced coma to
      show that neuronal activity en route to consciousness is confined to a low
      dimensional subspace. In this subspace, neuronal activity forms discrete
      metastable states persistent on the scale of minutes. The network of transitions
      that links these metastable states is structured such that some states form hubs
      that connect groups of otherwise disconnected states. Although many paths through
      the network are possible, to ultimately enter the activity state compatible with
      consciousness, the brain must first pass through these hubs in an orderly
      fashion. This organization of metastable states, along with dramatic
      dimensionality reduction, significantly simplifies the task of sampling the
      parameter space to recover the state consistent with wakefulness on a
      physiologically relevant timescale. 

PMID- 24927559
TI  - Nod/Ripk2 signaling in dendritic cells activates IL-17A-secreting innate lymphoid
      cells and drives colitis in T-bet-/-.Rag2-/- (TRUC) mice.
AB  - T-bet(-/-).Rag2(-/-) (TRUC) mice spontaneously develop microbiota-driven, TNF
      mediated large bowel inflammation that resembles human ulcerative colitis. We
      show here that IL-23 and IL-1-dependent secretion of IL-17A by innate lymphoid
      cells (ILCs; defined as CD45(+)lin(-)Thy1(hi)NKp46(-)) is a second critical
      pathway in this model. Using an in vitro coculture system of bone marrow-derived
      dendritic cells (DCs) and freshly isolated FACS-purified ILCs, we demonstrate
      that IL-23 and IL-1 secreted by DCs in response to microbial stimulation work
      together to induce IL-17A production by ILCs. TNF is not required for IL-17A
      secretion by ILCs in vitro but synergizes with IL-17A to induce the expression of
      neutrophil-attracting chemokines. Upstream, activation of the IL-23/IL-17A axis
      is regulated by nucleotide-binding oligomerization domain containing
      (Nod)/receptor-interacting serine-threonine kinase 2 (Ripk2) signals in DCs.
      Genetic ablation of the Nod/Ripk2 signaling pathway protects TRUC mice from
      developing colitis without affecting the colitogenicity of the intestinal
      microbiota. Our data provide insight into the complex network of interactions
      between IL-17A-secreting ILCs and other components of the innate immune system in
      the development of colitis. 

PMID- 24927560
TI  - Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing
      antibodies and confers heterologous protection.
AB  - Influenza hemagglutinin (HA) is the primary target of the humoral response during
      infection/vaccination. Current influenza vaccines typically fail to elicit/boost
      broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy.
      Although several bnAbs bind to the conserved stem domain of HA, focusing the
      immune response to this conserved stem in the presence of the immunodominant,
      variable head domain of HA is challenging. We report the design of a
      thermotolerant, disulfide-free, and trimeric HA stem-fragment immunogen which
      mimics the native, prefusion conformation of HA and binds conformation specific
      bnAbs with high affinity. The immunogen elicited bnAbs that neutralized highly
      divergent group 1 (H1 and H5 subtypes) and 2 (H3 subtype) influenza virus strains
      in vitro. Stem immunogens designed from unmatched, highly drifted influenza
      strains conferred robust protection against a lethal heterologous A/Puerto
      Rico/8/34 virus challenge in vivo. Soluble, bacterial expression of such designed
      immunogens allows for rapid scale-up during pandemic outbreaks. 

PMID- 24927561
TI  - Self-assembly of amphiphilic Janus dendrimers into uniform onion-like
      dendrimersomes with predictable size and number of bilayers.
AB  - A constitutional isomeric library synthesized by a modular approach has been used
      to discover six amphiphilic Janus dendrimer primary structures, which self
      assemble into uniform onion-like vesicles with predictable dimensions and number
      of internal bilayers. These vesicles, denoted onion-like dendrimersomes, are
      assembled by simple injection of a solution of Janus dendrimer in a water
      miscible solvent into water or buffer. These dendrimersomes provide mimics of
      double-bilayer and multibilayer biological membranes with dimensions and number
      of bilayers predicted by the Janus compound concentration in water. The simple
      injection method of preparation is accessible without any special equipment,
      generating uniform vesicles, and thus provides a promising tool for fundamental
      studies as well as technological applications in nanomedicine and other fields. 

PMID- 24927562
TI  - Targeting and in vivo imaging of non-small-cell lung cancer using nebulized
      multimodal contrast agents.
AB  - One of the main reasons for the dismal prognosis of lung cancer is related to the
      late diagnosis of this pathology. In this work, we evaluated the potential of
      optimized lung MRI techniques and nebulized ultrasmall multimodal gadolinium
      based contrast agents [ultrasmall rigid platforms (USRPs)] as a completely
      noninvasive approach for non-small-cell lung cancer (NSCLC) in vivo detection. A
      mouse model of NSCLC expressing the luciferase gene was developed. Ultrashort
      echo-time free-breathing MRI acquisitions were performed before and after i.v. or
      intrapulmonary administration of the nanoparticles to identify and segment the
      tumor. After orotracheal or i.v. administration of USRPs, an excellent
      colocalization of the position the tumor with MRI, bioluminescence and
      fluorescence reflectance imaging, and histology was observed in all mice.
      Significantly higher signal enhancements and contrast-to-noise ratios were
      observed with orotracheal administration using lower doses, reducing the toxicity
      issues and the interobserver variability in tumor detection. The observations
      suggested the existence of an unknown original mechanism (different from the
      enhanced permeability and retention effect) responsible for this phenomenon. MRI
      and USRPs were shown to be powerful imaging tools able to detect, quantify, and
      longitudinally monitor the development of submillimetric NSCLCs. The absence of
      ionizing radiation and high resolution MRI, along with the complete
      noninvasiveness and good reproducibility of the proposed protocol, make this
      technique potentially translatable to humans. To our knowledge this is the first
      time that the advantages of an orotracheal administration route are demonstrated
      for the investigation of the pathomorphological changes due to NSCLCs. 

PMID- 24927564
TI  - Linear integration of spine Ca2+ signals in layer 4 cortical neurons in vivo.
AB  - Sensory information reaches the cortex through synchronously active thalamic
      axons, which provide a strong drive to layer 4 (L4) cortical neurons. Because of
      technical limitations, the dendritic signaling processes underlying the rapid and
      efficient activation of L4 neurons in vivo remained unknown. Here we introduce an
      approach that allows the direct monitoring of single dendritic spine Ca(2+)
      signals in L4 spiny stellate cells of the vibrissal mouse cortex in vivo. Our
      results demonstrate that activation of N-methyl-D-aspartate (NMDA) receptors is
      required for sensory-evoked action potential (AP) generation in these neurons. By
      analyzing NMDA receptor-mediated Ca(2+) signaling, we identify whisker
      stimulation-evoked large responses in a subset of dendritic spines. These sensory
      stimulation-activated spines, representing predominantly thalamo-cortical input
      sites, were denser at proximal dendritic regions. The amplitude of sensory-evoked
      spine Ca(2+) signals was independent of the activity of neighboring spines,
      without evidence for cooperativity. Furthermore, we found that spine Ca(2+)
      signals evoked by back-propagating APs sum linearly with sensory-evoked synaptic
      Ca(2+) signals. Thus, our results identify in sensory information-receiving L4
      cortical neurons a linear mode of dendritic integration that underlies the rapid
      and reliable transfer of peripheral signals to the cortical network. 

PMID- 24927563
TI  - Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer.
AB  - The transcription factor c-MYC is stabilized and activated by phosphorylation at
      serine 62 (S62) in breast cancer. Protein phosphatase 2A (PP2A) is a critical
      negative regulator of c-MYC through its ability to dephosphorylate S62. By
      inactivating c-MYC and other key signaling pathways, PP2A plays an important
      tumor suppressor function. Two endogenous inhibitors of PP2A, I2PP2A, Inhibitor-2
      of PP2A (SET oncoprotein) and cancerous inhibitor of PP2A (CIP2A), inactivate
      PP2A and are overexpressed in several tumor types. Here we show that SET is
      overexpressed in about 50-60% and CIP2A in about 90% of breast cancers. Knockdown
      of SET or CIP2A reduces the tumorigenic potential of breast cancer cell lines
      both in vitro and in vivo. Treatment of breast cancer cells in vitro or in vivo
      with OP449, a novel SET antagonist, also decreases the tumorigenic potential of
      breast cancer cells and induces apoptosis. We show that this is, at least in
      part, due to decreased S62 phosphorylation of c-MYC and reduced c-MYC activity
      and target gene expression. Because of the ubiquitous expression and tumor
      suppressor activity of PP2A in cells, as well as the critical role of c-MYC in
      human cancer, we propose that activation of PP2A (here accomplished through
      antagonizing endogenous inhibitors) could be a novel antitumor strategy to
      posttranslationally target c-MYC in breast cancer. 

PMID- 24927565
TI  - Distinct phases in the positive selection of CD8+ T cells distinguished by
      intrathymic migration and T-cell receptor signaling patterns.
AB  - Positive selection of CD8 T cells in the thymus is thought to be a multistep
      process lasting 3-4 d; however, the discrete steps involved are poorly
      understood. Here, we examine phenotypic changes, calcium signaling, and
      intrathymic migration in a synchronized cohort of MHC class I-specific thymocytes
      undergoing positive selection in situ. Transient elevations in intracellular
      calcium concentration ([Ca(2+)]i) and migratory pauses occurred throughout the
      first 24 h of positive selection, becoming progressively briefer and accompanied
      by a gradual shift in basal [Ca(2+)]i over time. Changes in chemokine-receptor
      expression and relocalization from the cortex to medulla occurred between 12 and
      24 h after the initial encounter with positive-selecting ligands, a time frame at
      which the majority of thymocytes retain CD4 and CD8 expression and still require
      T-cell receptor (TCR) signaling to efficiently complete positive selection. Our
      results identify distinct phases in the positive selection of MHC class I
      specific thymocytes that are distinguished by their TCR-signaling pattern and
      intrathymic location and provide a framework for understanding the multistep
      process of positive selection in the thymus. 

PMID- 24927566
TI  - Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity
      carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide.
AB  - We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530
      (a retinoic acid receptor gamma selective agonist), and the combination of these
      two drugs for the prevention of oral carcinogenesis induced by the carcinogen 4
      nitroquinoline 1-oxide (4-NQO) in a mouse model of human oral-cavity and
      esophageal squamous-cell carcinoma previously generated in our laboratory. We
      observed decreased numbers of neoplastic tongue lesions and reduced lesion
      severity in the 4-NQO plus CD1530 (4N+C) and 4-NQO plus bexarotene plus CD1530
      (4N+B+C) groups compared with the 4-NQO group. RNA-Seq analyses showed increases
      in transcripts in cell proliferation/cell cycle progression pathways in the 4-NQO
      vs. the untreated group. In addition, beta-catenin and matrix metallopeptidase 9
      (MMP9) protein levels and reactive oxygen species (ROS), as assessed by 4
      hydroxynonenal (4-HNE) staining, were elevated in tongue tissues 17 wk after the
      termination of the 4-NQO treatment. The 4N+B, 4N+C, and 4N+B+C groups showed
      dramatically lower levels of beta-catenin, MMP9, and 4-HNE staining compared with
      the 4-NQO group. The major reduction in 4-HNE staining in the retinoid treatment
      groups suggests a novel mechanism of action, reduction of ROS, by which
      bexarotene and CD1530 inhibit carcinogenesis. 

PMID- 24927567
TI  - The endocannabinoid 2-AG controls skeletal muscle cell differentiation via CB1
      receptor-dependent inhibition of Kv7 channels.
AB  - Little is known of the involvement of endocannabinoids and cannabinoid receptors
      in skeletal muscle cell differentiation. We report that, due to changes in the
      expression of genes involved in its metabolism, the levels of the endocannabinoid
      2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in
      vitro from murine C2C12 myoblasts and during mouse muscle growth in vivo. The
      endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide,
      prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1
      antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG
      also inhibits differentiation of primary human satellite cells. Muscle fascicles
      from CB1 knockout embryos contain more muscle fibers, and postnatal mice show
      muscle fibers of an increased diameter relative to wild-type littermates.
      Inhibition of Kv7.4 channel activity, which plays a permissive role in myogenesis
      and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the
      effects of 2-AG. We find that CB1 stimulation reduces both total and Kv7.4-bound
      PIP2 levels in C2C12 cells and inhibits Kv7.4 currents in transfected CHO cells.
      We suggest that 2-AG is an endogenous repressor of myoblast differentiation via
      CB1-mediated inhibition of Kv7.4 channels. 

PMID- 24927568
TI  - Probing nuclear pore complex architecture with proximity-dependent biotinylation.
AB  - Proximity-dependent biotin identification (BioID) is a method for identifying
      protein associations that occur in vivo. By fusing a promiscuous biotin ligase to
      a protein of interest expressed in living cells, BioID permits the labeling of
      proximate proteins during a defined labeling period. In this study we used BioID
      to study the human nuclear pore complex (NPC), one of the largest macromolecular
      assemblies in eukaryotes. Anchored within the nuclear envelope, NPCs mediate the
      nucleocytoplasmic trafficking of numerous cellular components. We applied BioID
      to constituents of the Nup107-160 complex and the Nup93 complex, two conserved
      NPC subcomplexes. A strikingly different set of NPC constituents was detected
      depending on the position of these BioID-fusion proteins within the NPC. By
      applying BioID to several constituents located throughout the extremely stable
      Nup107-160 subcomplex, we refined our understanding of this highly conserved
      subcomplex, in part by demonstrating a direct interaction of Nup43 with Nup85.
      Furthermore, by using the extremely stable Nup107-160 structure as a molecular
      ruler, we defined the practical labeling radius of BioID. These studies further
      our understanding of human NPC organization and demonstrate that BioID is a
      valuable tool for exploring the constituency and organization of large protein
      assemblies in living cells. 

PMID- 24927569
TI  - Notch regulation of myogenic versus endothelial fates of cells that migrate from
      the somite to the limb.
AB  - Multipotent Pax3-positive (Pax3(+)) cells in the somites give rise to skeletal
      muscle and to cells of the vasculature. We had previously proposed that this cell
      fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this
      study, we report that the Notch pathway promotes vascular versus skeletal muscle
      cell fates. Overactivating the Notch pathway specifically in Pax3(+) progenitors,
      via a conditional Pax3(NICD) allele, results in an increase of the number of
      smooth muscle and endothelial cells contributing to the aorta. At limb level,
      Pax3(+) cells in the somite give rise to skeletal muscles and to a subpopulation
      of endothelial cells in blood vessels of the limb. We now demonstrate that in
      addition to the inhibitory role of Notch signaling on skeletal muscle cell
      differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes
      the endothelial versus myogenic cell fate, before migration to the limb, in
      multipotent Pax3(+) cells in the somite of the mouse embryo. 

PMID- 24927570
TI  - A piggyBac route to transgenic honeybees.

PMID- 24927571
TI  - Topologically protected states in one-dimensional continuous systems and Dirac
      points.
AB  - We study a class of periodic Schrodinger operators on R that have Dirac points.
      The introduction of an "edge" via adiabatic modulation of a periodic potential by
      a domain wall results in the bifurcation of spatially localized "edge states,"
      associated with the topologically protected zero-energy mode of an asymptotic one
      dimensional Dirac operator. The bound states we construct can be realized as
      highly robust transverse-magnetic electromagnetic modes for a class of photonic
      waveguides with a phase defect. Our model captures many aspects of the phenomenon
      of topologically protected edge states for 2D bulk structures such as the
      honeycomb structure of graphene. 

PMID- 24927572
TI  - GroEL from the endosymbiont Buchnera aphidicola betrays the aphid by triggering
      plant defense.
AB  - Aphids are sap-feeding plant pests and harbor the endosymbiont Buchnera
      aphidicola, which is essential for their fecundity and survival. During plant
      penetration and feeding, aphids secrete saliva that contains proteins predicted
      to alter plant defenses and metabolism. Plants recognize microbe-associated
      molecular patterns and induce pattern-triggered immunity (PTI). No aphid
      associated molecular pattern has yet been identified. By mass spectrometry, we
      identified in saliva from potato aphids (Macrosiphum euphorbiae) 105 proteins,
      some of which originated from Buchnera, including the chaperonin GroEL. Because
      GroEL is a widely conserved bacterial protein with an essential function, we
      tested its role in PTI. Applying or infiltrating GroEL onto Arabidopsis
      (Arabidopsis thaliana) leaves induced oxidative burst and expression of PTI early
      marker genes. These GroEL-induced defense responses required the known coreceptor
      BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1. In addition, in
      transgenic Arabidopsis plants, inducible expression of groEL activated PTI marker
      gene expression. Moreover, Arabidopsis plants expressing groEL displayed reduced
      fecundity of the green peach aphid (Myzus persicae), indicating enhanced
      resistance against aphids. Furthermore, delivery of GroEL into tomato (Solanum
      lycopersicum) or Arabidopsis through Pseudomonas fluorescens, engineered to
      express the type III secretion system, also reduced potato aphid and green peach
      aphid fecundity, respectively. Collectively our data indicate that GroEL is a
      molecular pattern that triggers PTI. 

PMID- 24927573
TI  - Energy landscape of self-assembled superlattices of PbSe nanocrystals.
AB  - Self-assembly of nanocrystals (NCs) into superlattices is an intriguing
      multiscale phenomenon that may lead to materials with novel collective
      properties, in addition to the unique properties of individual NCs compared with
      their bulk counterparts. By using different dispersion solvents, we synthesized
      three types of PbSe NC superlattices--body-centered cubic (bcc), body-centered
      tetragonal (bct), and face-centered cubic (fcc)--as confirmed by synchrotron
      small-angle X-ray scattering. Solution calorimetric measurements in hexane show
      that the enthalpy of formation of the superlattice from dispersed NCs is on the
      order of -2 kJ/mol. The calorimetric measurements reveal that the bcc
      superlattice is the energetically most stable polymorph, with the bct being 0.32
      and the fcc 0.55 kJ/mol higher in enthalpy. This stability sequence is consistent
      with the decreased packing efficiency of PbSe NCs from bcc (17.2%) to bct (16.0%)
      and to fcc (15.2%). The small enthalpy differences among the three polymorphs
      confirm a closely spaced energy landscape and explain the ease of formation of
      different NC superlattices at slightly different synthesis conditions.

PMID- 24927574
TI  - Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA-like
      structural element in the ribosomal decoding center.
AB  - In cap-dependent translation initiation, the open reading frame (ORF) of mRNA is
      established by the placement of the AUG start codon and initiator tRNA in the
      ribosomal peptidyl (P) site. Internal ribosome entry sites (IRESs) promote
      translation of mRNAs in a cap-independent manner. We report two structures of the
      ribosome-bound Taura syndrome virus (TSV) IRES belonging to the family of
      Dicistroviridae intergenic IRESs. Intersubunit rotational states differ in these
      structures, suggesting that ribosome dynamics play a role in IRES translocation.
      Pseudoknot I of the IRES occupies the ribosomal decoding center at the aminoacyl
      (A) site in a manner resembling that of the tRNA anticodon-mRNA codon. The
      structures reveal that the TSV IRES initiates translation by a previously unseen
      mechanism, which is conceptually distinct from initiator tRNA-dependent
      mechanisms. Specifically, the ORF of the IRES-driven mRNA is established by the
      placement of the preceding tRNA-mRNA-like structure in the A site, whereas the
      40S P site remains unoccupied during this initial step. 

PMID- 24927575
TI  - Mechanism of staphylococcal multiresistance plasmid replication origin assembly
      by the RepA protein.
AB  - The staphylococcal multiresistance plasmids are key contributors to the alarming
      rise in bacterial multidrug resistance. A conserved replication initiator, RepA,
      encoded on these plasmids is essential for their propagation. RepA proteins
      consist of flexibly linked N-terminal (NTD) and C-terminal (CTD) domains. Despite
      their essential role in replication, the molecular basis for RepA function is
      unknown. Here we describe a complete structural and functional dissection of RepA
      proteins. Unexpectedly, both the RepA NTD and CTD show similarity to the
      corresponding domains of the bacterial primosome protein, DnaD. Although the RepA
      and DnaD NTD both contain winged helix-turn-helices, the DnaD NTD self-assembles
      into large scaffolds whereas the tetrameric RepA NTD binds DNA iterons using a
      newly described DNA binding mode. Strikingly, structural and atomic force
      microscopy data reveal that the NTD tetramer mediates DNA bridging, suggesting a
      molecular mechanism for origin handcuffing. Finally, data show that the RepA CTD
      interacts with the host DnaG primase, which binds the replicative helicase. Thus,
      these combined data reveal the molecular mechanism by which RepA mediates the
      specific replicon assembly of staphylococcal multiresistant plasmids. 

PMID- 24927576
TI  - Structural and mechanistic studies of polymerase eta bypass of phenanthriplatin
      DNA damage.
AB  - Platinum drugs are a mainstay of anticancer chemotherapy. Nevertheless, tumors
      often display inherent or acquired resistance to platinum-based treatments,
      prompting the search for new compounds that do not exhibit cross-resistance with
      current therapies. Phenanthriplatin, cis
      diamminephenanthridinechloroplatinum(II), is a potent monofunctional platinum
      complex that displays a spectrum of activity distinct from those of the
      clinically approved platinum drugs. Inhibition of RNA polymerases by
      phenanthriplatin lesions has been implicated in its mechanism of action. The
      present study evaluates the ability of phenanthriplatin lesions to inhibit DNA
      replication, a function disrupted by traditional platinum drugs. Phenanthriplatin
      lesions effectively inhibit DNA polymerases nu, zeta, and kappa and the Klenow
      fragment. In contrast to results obtained with DNA damaged by cisplatin, all of
      these polymerases were capable of inserting a base opposite a phenanthriplatin
      lesion, but only Pol eta, an enzyme efficient in translesion synthesis, was able
      to fully bypass the adduct, albeit with low efficiency. X-ray structural
      characterization of Pol eta complexed with site-specifically platinated DNA at
      both the insertion and +1 extension steps reveals that phenanthriplatin on DNA
      interacts with and inhibits Pol eta in a manner distinct from that of cisplatin
      DNA adducts. Unlike cisplatin and oxaliplatin, the efficacies of which are
      influenced by Pol eta expression, phenanthriplatin is highly toxic to both Pol
      eta+ and Pol eta- cells. Given that increased expression of Pol eta is a known
      mechanism by which cells resist cisplatin treatment, phenanthriplatin may be
      valuable in the treatment of cancers that are, or can easily become, resistant to
      cisplatin. 

PMID- 24927577
TI  - Packing density of rigid aggregates is independent of scale.
AB  - Large planetary seedlings, comets, microscale pharmaceuticals, and nanoscale soot
      particles are made from rigid, aggregated subunits that are compacted under low
      compression into larger structures spanning over 10 orders of magnitude in
      dimensional space. Here, we demonstrate that the packing density (thetaf) of
      compacted rigid aggregates is independent of spatial scale for systems under weak
      compaction. The thetaf of rigid aggregated structures across six orders of
      magnitude were measured using nanoscale spherical soot aerosol composed of
      aggregates with ~ 17-nm monomeric subunits and aggregates made from uniform
      monomeric 6-mm spherical subunits at the macroscale. We find thetaf = 0.36 +/-
      0.02 at both dimensions. These values are remarkably similar to thetaf observed
      for comet nuclei and measured values of other rigid aggregated systems across a
      wide variety of spatial and formative conditions. We present a packing model that
      incorporates the aggregate morphology and show that thetaf is independent of both
      monomer and aggregate size. These observations suggest that the thetaf of rigid
      aggregates subject to weak compaction forces is independent of spatial dimension
      across varied formative conditions.

PMID- 24927578
TI  - Evidence for elevated and spatially variable geothermal flux beneath the West
      Antarctic Ice Sheet.
AB  - Heterogeneous hydrologic, lithologic, and geologic basal boundary conditions can
      exert strong control on the evolution, stability, and sea level contribution of
      marine ice sheets. Geothermal flux is one of the most dynamically critical ice
      sheet boundary conditions but is extremely difficult to constrain at the scale
      required to understand and predict the behavior of rapidly changing glaciers.
      This lack of observational constraint on geothermal flux is particularly
      problematic for the glacier catchments of the West Antarctic Ice Sheet within the
      low topography of the West Antarctic Rift System where geothermal fluxes are
      expected to be high, heterogeneous, and possibly transient. We use airborne radar
      sounding data with a subglacial water routing model to estimate the distribution
      of basal melting and geothermal flux beneath Thwaites Glacier, West Antarctica.
      We show that the Thwaites Glacier catchment has a minimum average geothermal flux
      of ~ 114 +/- 10 mW/m(2) with areas of high flux exceeding 200 mW/m(2) consistent
      with hypothesized rift-associated magmatic migration and volcanism. These areas
      of highest geothermal flux include the westernmost tributary of Thwaites Glacier
      adjacent to the subaerial Mount Takahe volcano and the upper reaches of the
      central tributary near the West Antarctic Ice Sheet Divide ice core drilling
      site.

PMID- 24927579
TI  - Anthropogenic changes in sodium affect neural and muscle development in
      butterflies.
AB  - The development of organisms is changing drastically because of anthropogenic
      changes in once-limited nutrients. Although the importance of changing
      macronutrients, such as nitrogen and phosphorus, is well-established, it is less
      clear how anthropogenic changes in micronutrients will affect organismal
      development, potentially changing dynamics of selection. We use butterflies as a
      study system to test whether changes in sodium availability due to road salt
      runoff have significant effects on the development of sodium-limited traits, such
      as neural and muscle tissue. We first document how road salt runoff can elevate
      sodium concentrations in the tissue of some plant groups by 1.5-30 times. Using
      monarch butterflies reared on roadside- and prairie-collected milkweed, we then
      show that road salt runoff can result in increased muscle mass (in males) and
      neural investment (in females). Finally, we use an artificial diet manipulation
      in cabbage white butterflies to show that variation in sodium chloride per se
      positively affects male flight muscle and female brain size. Variation in sodium
      not only has different effects depending on sex, but also can have opposing
      effects on the same tissue: across both species, males increase investment in
      flight muscle with increasing sodium, whereas females show the opposite pattern.
      Taken together, our results show that anthropogenic changes in sodium
      availability can affect the development of traits in roadside-feeding herbivores.
      This research suggests that changing micronutrient availability could alter
      selection on foraging behavior for some roadside-developing invertebrates.

PMID- 24927581
TI  - QnAs with Thomas Jessell.

PMID- 24927580
TI  - Perilipins 2 and 3 lack a carboxy-terminal domain present in perilipin 1 involved
      in sequestering ABHD5 and suppressing basal lipolysis.
AB  - Lipid droplets (LDs) are a conserved feature of most organisms. Vertebrate
      adipocytes have evolved to efficiently store and release lipids for the whole
      organism from a single droplet. Perilipin 1, the most abundant lipid-coat protein
      in adipocytes, plays a key role in regulating lipolysis. In other tissues such as
      liver and muscle, LDs serve very different biological functions, buffering
      surplus lipids for subsequent oxidation or export. These tissues express
      perilipins 2 or 3, rather than perilipin 1. We sought to understand the role of
      perilipins 2 and 3 in regulating basal lipolysis. Bimolecular fluorescence
      complementation studies suggested that whereas perilipin 1 prevents the
      activation of adipose tissue triacylglycerol lipase by its coactivator, AB
      hydrolase domain containing-5 (ABHD5), perilipins 2 and 3 do so less effectively.
      These differences are mediated by a conserved region within the carboxy terminus
      of perilipin 1 that binds and stabilizes ABHD5 by retarding its degradation by
      the proteosome. Chimeric proteins generated by fusing the carboxy terminus of
      perilipin 1 to the amino terminus of perilipins 2 or 3 stabilize ABHD5 and
      suppress basal lipolysis more effectively than WT perilipins 2 or 3. Furthermore,
      knockdown of perilipin 1 in adipocytes leads to replacement of perilipin 2 on
      LDs. In these cells we observed reduced ABHD5 expression and LD localization and
      a corresponding increase in basal lipolysis. Collectively these data suggest that
      whereas perilipin 1 potently suppresses basal lipolysis in adipocytes, perilipins
      2 and 3 facilitate higher rates of basal lipolysis in other tissues where
      constitutive traffic of fatty acids via LDs is a necessary step in their
      metabolism. 

PMID- 24927582
TI  - Correcting direct effects of ethanol on translation and transcription machinery
      confers ethanol tolerance in bacteria.
AB  - The molecular mechanisms of ethanol toxicity and tolerance in bacteria, although
      important for biotechnology and bioenergy applications, remain incompletely
      understood. Genetic studies have identified potential cellular targets for
      ethanol and have revealed multiple mechanisms of tolerance, but it remains
      difficult to separate the direct and indirect effects of ethanol. We used
      adaptive evolution to generate spontaneous ethanol-tolerant strains of
      Escherichia coli, and then characterized mechanisms of toxicity and resistance
      using genome-scale DNAseq, RNAseq, and ribosome profiling coupled with specific
      assays of ribosome and RNA polymerase function. Evolved alleles of metJ, rho, and
      rpsQ recapitulated most of the observed ethanol tolerance, implicating
      translation and transcription as key processes affected by ethanol. Ethanol
      induced miscoding errors during protein synthesis, from which the evolved rpsQ
      allele protected cells by increasing ribosome accuracy. Ribosome profiling and
      RNAseq analyses established that ethanol negatively affects transcriptional and
      translational processivity. Ethanol-stressed cells exhibited ribosomal stalling
      at internal AUG codons, which may be ameliorated by the adaptive inactivation of
      the MetJ repressor of methionine biosynthesis genes. Ethanol also caused aberrant
      intragenic transcription termination for mRNAs with low ribosome density, which
      was reduced in a strain with the adaptive rho mutation. Furthermore, ethanol
      inhibited transcript elongation by RNA polymerase in vitro. We propose that
      ethanol-induced inhibition and uncoupling of mRNA and protein synthesis through
      direct effects on ribosomes and RNA polymerase conformations are major
      contributors to ethanol toxicity in E. coli, and that adaptive mutations in metJ,
      rho, and rpsQ help protect these central dogma processes in the presence of
      ethanol. 

PMID- 24927583
TI  - Global metaanalysis of the nonlinear response of soil nitrous oxide (N2O)
      emissions to fertilizer nitrogen.
AB  - Nitrous oxide (N2O) is a potent greenhouse gas (GHG) that also depletes
      stratospheric ozone. Nitrogen (N) fertilizer rate is the best single predictor of
      N2O emissions from agricultural soils, which are responsible for ~ 50% of the
      total global anthropogenic flux, but it is a relatively imprecise estimator.
      Accumulating evidence suggests that the emission response to increasing N input
      is exponential rather than linear, as assumed by Intergovernmental Panel on
      Climate Change methodologies. We performed a metaanalysis to test the
      generalizability of this pattern. From 78 published studies (233 site-years) with
      at least three N-input levels, we calculated N2O emission factors (EFs) for each
      nonzero input level as a percentage of N input converted to N2O emissions. We
      found that the N2O response to N inputs grew significantly faster than linear for
      synthetic fertilizers and for most crop types. N-fixing crops had a higher rate
      of change in EF (DeltaEF) than others. A higher DeltaEF was also evident in soils
      with carbon >1.5% and soils with pH <7, and where fertilizer was applied only
      once annually. Our results suggest a general trend of exponentially increasing
      N2O emissions as N inputs increase to exceed crop needs. Use of this knowledge in
      GHG inventories should improve assessments of fertilizer-derived N2O emissions,
      help address disparities in the global N2O budget, and refine the accuracy of N2O
      mitigation protocols. In low-input systems typical of sub-Saharan Africa, for
      example, modest N additions will have little impact on estimated N2O emissions,
      whereas equivalent additions (or reductions) in excessively fertilized systems
      will have a disproportionately major impact.

PMID- 24927584
TI  - Evolutionary developmental transcriptomics reveals a gene network module
      regulating interspecific diversity in plant leaf shape.
AB  - Despite a long-standing interest in the genetic basis of morphological diversity,
      the molecular mechanisms that give rise to developmental variation are
      incompletely understood. Here, we use comparative transcriptomics coupled with
      the construction of gene coexpression networks to predict a gene regulatory
      network (GRN) for leaf development in tomato and two related wild species with
      strikingly different leaf morphologies. The core network in the leaf
      developmental GRN contains regulators of leaf morphology that function in global
      cell proliferation with peripheral gene network modules (GNMs). The BLADE-ON
      PETIOLE (BOP) transcription factor in one GNM controls the core network by
      altering effective concentration of the KNOTTED-like HOMEOBOX gene product.
      Comparative network analysis and experimental perturbations of BOP levels suggest
      that variation in BOP expression could explain the diversity in leaf complexity
      among these species through dynamic rewiring of interactions in the GRN. The
      peripheral location of the BOP-containing GNM in the leaf developmental GRN and
      the phenotypic mimics of evolutionary diversity caused by alteration in BOP
      levels identify a key role for this GNM in canalizing the leaf morphospace by
      modifying the maturation schedule of leaves to create morphological diversity. 

PMID- 24927586
TI  - Correlating the motion of electrons and nuclei with two-dimensional electronic
      vibrational spectroscopy.
AB  - Multidimensional nonlinear spectroscopy, in the electronic and vibrational
      regimes, has reached maturity. To date, no experimental technique has combined
      the advantages of 2D electronic spectroscopy and 2D infrared spectroscopy,
      monitoring the evolution of the electronic and nuclear degrees of freedom
      simultaneously. The interplay and coupling between the electronic state and
      vibrational manifold is fundamental to understanding ensuing nonradiative
      pathways, especially those that involve conical intersections. We have developed
      a new experimental technique that is capable of correlating the electronic and
      vibrational degrees of freedom: 2D electronic-vibrational spectroscopy (2D-EV).
      We apply this new technique to the study of the 4-(di-cyanomethylene)-2-methyl-6
      p-(dimethylamino)styryl-4H-pyran (DCM) laser dye in deuterated dimethyl sulfoxide
      and its excited state relaxation pathways. From 2D-EV spectra, we elucidate a
      ballistic mechanism on the excited state potential energy surface whereby
      molecules are almost instantaneously projected uphill in energy toward a
      transition state between locally excited and charge-transfer states, as evidenced
      by a rapid blue shift on the electronic axis of our 2D-EV spectra. The change in
      minimum energy structure in this excited state nonradiative crossing is evident
      as the central frequency of a specific vibrational mode changes on a many
      picoseconds timescale. The underlying electronic dynamics, which occur on the
      hundreds of femtoseconds timescale, drive the far slower ensuing nuclear motions
      on the excited state potential surface, and serve as a excellent illustration for
      the unprecedented detail that 2D-EV will afford to photochemical reaction
      dynamics. 

PMID- 24927585
TI  - Probing the paramyxovirus fusion (F) protein-refolding event from pre- to
      postfusion by oxidative footprinting.
AB  - To infect a cell, the Paramyxoviridae family of enveloped viruses relies on the
      coordinated action of a receptor-binding protein (variably HN, H, or G) and a
      more conserved metastable fusion protein (F) to effect membrane fusion and allow
      genomic transfer. Upon receptor binding, HN (H or G) triggers F to undergo an
      extensive refolding event to form a stable postfusion state. Little is known
      about the intermediate states of the F refolding process. Here, a soluble form of
      parainfluenza virus 5 F was triggered to refold using temperature and was
      footprinted along the refolding pathway using fast photochemical oxidation of
      proteins (FPOP). Localization of the oxidative label to solvent-exposed side
      chains was determined by high-resolution MS/MS. Globally, metastable prefusion F
      is oxidized more extensively than postfusion F, indicating that the prefusion
      state is more exposed to solvent and is more flexible. Among the first peptides
      to be oxidatively labeled after temperature-induced triggering is the hydrophobic
      fusion peptide. A comparison of peptide oxidation levels with the values of
      solvent-accessible surface area calculated from molecular dynamics simulations of
      available structural data reveals regions of the F protein that lie at the heart
      of its prefusion metastability. The strong correlation between the regions of F
      that experience greater-than-expected oxidative labeling and epitopes for
      neutralizing antibodies suggests that FPOP has a role in guiding the development
      of targeted therapeutics. Analysis of the residue levels of labeled F
      intermediates provides detailed insights into the mechanics of this critical
      refolding event. 

PMID- 24927587
TI  - Let's exploit available knowledge on vegetation fluorescence.

PMID- 24927588
TI  - Resting GABA and glutamate concentrations do not predict visual gamma frequency
      or amplitude.
AB  - Gamma band oscillations arise in neuronal networks of interconnected GABAergic
      interneurons and excitatory pyramidal cells. A previous study found a correlation
      between visual gamma peak frequency, as measured with magnetoencephalography, and
      resting GABA levels, as measured with magnetic resonance spectroscopy (MRS), in
      12 healthy volunteers. If true, this would allow studies in clinical populations
      testing modulation of this relationship, but this finding has not been
      replicated. We addressed this important question by measuring gamma oscillations
      and GABA, as well as glutamate, in 50 healthy volunteers. Visual gamma activity
      was evoked using an established gratings paradigm, and we applied a beamformer
      spatial filtering technique to extract source-reconstructed gamma peak frequency
      and amplitude from the occipital lobe. We determined gamma peak frequency and
      amplitude from the location with maximal activation and from the location of the
      MRS voxel to assess the relationship of GABA with gamma. Gamma peak frequency was
      estimated from the highest value of the raw spectra and by a Gaussian fit to the
      spectra. MRS data were acquired from occipital cortex. We did not replicate the
      previously found correlation between gamma peak frequency and GABA concentration.
      Calculation of a Bayes factor provided strong evidence in favor of the null
      hypothesis. We also did not find a correlation between gamma activity and
      glutamate or between gamma and the ratio of GABA/glutamate. Our results suggest
      that cortical gamma oscillations do not have a consistent, demonstrable
      relationship to excitatory/inhibitory network activity as proxied by MRS
      measurements of GABA and glutamate. 

PMID- 24927589
TI  - Badger responses to small-scale culling may compromise targeted control of bovine
      tuberculosis.
AB  - Where wildlife disease requires management, culling is frequently considered but
      not always effective. In the British Isles, control of cattle tuberculosis (TB)
      is hindered by infection in wild badger (Meles meles) populations. Large-scale
      badger culling can reduce the incidence of confirmed cattle TB, but these
      benefits are undermined by culling-induced changes in badger behavior (termed
      perturbation), which can increase transmission among badgers and from badgers to
      cattle. Test-vaccinate/remove (TVR) is a novel approach that entails testing
      individual badgers for infection, vaccinating test-negative animals, and killing
      test-positive animals. Imperfect capture success, diagnostic sensitivity, and
      vaccine effectiveness mean that TVR would be expected to leave some infected and
      some susceptible badgers in the population. Existing simulation models predict
      that TVR could reduce cattle TB if such small-scale culling causes no
      perturbation, but could increase cattle TB if considerable perturbation occurs.
      Using data from a long-term study, we show that past small-scale culling was
      significantly associated with four metrics of perturbation in badgers: expanded
      ranging, more frequent immigration, lower genetic relatedness, and elevated
      prevalence of Mycobacterium bovis, the causative agent of TB. Though we could not
      reject the hypothesis that culling up to three badgers per social group might
      avoid perturbation, we also could not reject the hypothesis that killing a single
      badger prompted detectable perturbation. When considered alongside existing model
      predictions, our findings suggest that implementation of TVR, scheduled for 2014,
      risks exacerbating the TB problem rather than controlling it. Ongoing illegal
      badger culling is likewise expected to increase cattle TB risks. 

PMID- 24927590
TI  - Seamless modification of wild-type induced pluripotent stem cells to the natural
      CCR5Delta32 mutation confers resistance to HIV infection.
AB  - Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp
      deletions (CCR5Delta32) are resistant to HIV-1 infection. In this study, we
      generated induced pluripotent stem cells (iPSCs) homozygous for the naturally
      occurring CCR5Delta32 mutation through genome editing of wild-type iPSCs using a
      combination of transcription activator-like effector nucleases (TALENs) or RNA
      guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9
      together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9-mediated
      double-strand DNA breaks resulted in up to 100% targeting of the colonies on one
      allele of which biallelic targeting occurred at an average of 14% with TALENs and
      33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced
      exactly the naturally occurring CCR5Delta32 mutation without detectable exogenous
      sequences. We differentiated these modified iPSCs into monocytes/macrophages and
      demonstrated their resistance to HIV-1 challenge. We propose that this strategy
      may provide an approach toward a functional cure of HIV-1 infection. 

PMID- 24927591
TI  - Maritime route of colonization of Europe.
AB  - The Neolithic populations, which colonized Europe approximately 9,000 y ago,
      presumably migrated from Near East to Anatolia and from there to Central Europe
      through Thrace and the Balkans. An alternative route would have been island
      hopping across the Southern European coast. To test this hypothesis, we analyzed
      genome-wide DNA polymorphisms on populations bordering the Mediterranean coast
      and from Anatolia and mainland Europe. We observe a striking structure
      correlating genes with geography around the Mediterranean Sea with characteristic
      east to west clines of gene flow. Using population network analysis, we also find
      that the gene flow from Anatolia to Europe was through Dodecanese, Crete, and the
      Southern European coast, compatible with the hypothesis that a maritime coastal
      route was mainly used for the migration of Neolithic farmers to Europe. 

PMID- 24927593
TI  - Social identification moderates the effect of crowd density on safety at the
      Hajj.
AB  - Crowd safety is a major concern for those attending and managing mass gatherings,
      such as the annual Hajj or pilgrimage to Mecca (also called Makkah). One threat
      to crowd safety at such events is crowd density. However, recent research also
      suggests that psychological membership of crowds can have positive benefits. We
      tested the hypothesis that the effect of density on safety might vary depending
      on whether there is shared social identification in the crowd. We surveyed 1,194
      pilgrims at the Holy Mosque, Mecca, during the 2012 Hajj. Analysis of the data
      showed that the negative effect of crowd density on reported safety was moderated
      by social identification with the crowd. Whereas low identifiers reported reduced
      safety with greater crowd density, high identifiers reported increased safety
      with greater crowd density. Mediation analysis suggested that a reason for these
      moderation effects was the perception that other crowd members were supportive.
      Differences in reported safety across national groups (Arab countries and Iran
      compared with the rest) were also explicable in terms of crowd identification and
      perceived support. These findings support a social identity account of crowd
      behavior and offer a novel perspective on crowd safety management. 

PMID- 24927592
TI  - Regulation of cell proliferation and migration by p62 through stabilization of
      Twist1.
AB  - The selective autophagy substrate p62 serves as a molecular link between
      autophagy and cancer. Suppression of autophagy causes p62 accumulation and
      thereby contributes to tumorigenesis. Here we demonstrate that autophagy
      deficiency promotes cell proliferation and migration through p62-dependent
      stabilization of the oncogenic transcription factor Twist1. p62 binds to Twist1
      and inhibits degradation of Twist1. In mice, p62 up-regulation promotes tumor
      cell growth and metastasis in a Twist1-dependent manner. Our findings demonstrate
      that Twist1 is a key downstream effector of p62 in regulation of cell
      proliferation and migration and suggest that targeting p62-mediated Twist1
      stabilization is a promising therapeutic strategy for prevention and treatment of
      cancer. 

PMID- 24927594
TI  - Sources and sinks of carbonyl sulfide in an agricultural field in the Southern
      Great Plains.
AB  - Net photosynthesis is the largest single flux in the global carbon cycle, but
      controls over its variability are poorly understood because there is no direct
      way of measuring it at the ecosystem scale. We report observations of ecosystem
      carbonyl sulfide (COS) and CO2 fluxes that resolve key gaps in an emerging
      framework for using concurrent COS and CO2 measurements to quantify terrestrial
      gross primary productivity. At a wheat field in Oklahoma we found that in the
      peak growing season the flux-weighted leaf relative uptake of COS and CO2 during
      photosynthesis was 1.3, at the lower end of values from laboratory studies, and
      varied systematically with light. Due to nocturnal stomatal conductance, COS
      uptake by vegetation continued at night, contributing a large fraction (29%) of
      daily net ecosystem COS fluxes. In comparison, the contribution of soil fluxes
      was small (1-6%) during the peak growing season. Upland soils are usually
      considered sinks of COS. In contrast, the well-aerated soil at the site switched
      from COS uptake to emissions at a soil temperature of around 15  degrees C. We
      observed COS production from the roots of wheat and other species and COS uptake
      by root-free soil up to a soil temperature of around 25  degrees C. Our dataset
      demonstrates that vegetation uptake is the dominant ecosystem COS flux in the
      peak growing season, providing support of COS as an independent tracer of
      terrestrial photosynthesis. However, the observation that ecosystems may become a
      COS source at high temperature needs to be considered in global modeling studies.

PMID- 24927595
TI  - Economic scarcity alters the perception of race.
AB  - When the economy declines, racial minorities are hit the hardest. Although
      existing explanations for this effect focus on institutional causes, recent
      psychological findings suggest that scarcity may also alter perceptions of race
      in ways that exacerbate discrimination. We tested the hypothesis that economic
      resource scarcity causes decision makers to perceive African Americans as
      "Blacker" and that this visual distortion elicits disparities in the allocation
      of resources. Studies 1 and 2 demonstrated that scarcity altered perceptions of
      race, lowering subjects' psychophysical threshold for seeing a mixed-race face as
      "Black" as opposed to "White." In studies 3 and 4, scarcity led subjects to
      visualize African American faces as darker and more "stereotypically Black,"
      compared with a control condition. When presented to naive subjects, face
      representations produced under scarcity elicited smaller allocations than control
      condition representations. Together, these findings introduce a novel perceptual
      account for the proliferation of racial disparities under economic scarcity. 

PMID- 24927596
TI  - Immersive audiomotor game play enhances neural and perceptual salience of weak
      signals in noise.
AB  - All sensory systems face the fundamental challenge of encoding weak signals in
      noisy backgrounds. Although discrimination abilities can improve with practice,
      these benefits rarely generalize to untrained stimulus dimensions. Inspired by
      recent findings that action video game training can impart a broader spectrum of
      benefits than traditional perceptual learning paradigms, we trained adult humans
      and mice in an immersive audio game that challenged them to forage for hidden
      auditory targets in a 2D soundscape. Both species learned to modulate their
      angular search vectors and target approach velocities based on real-time changes
      in the level of a weak tone embedded in broadband noise. In humans, mastery of
      this tone in noise task generalized to an improved ability to comprehend spoken
      sentences in speech babble noise. Neural plasticity in the auditory cortex of
      trained mice supported improved decoding of low-intensity sounds at the training
      frequency and an enhanced resistance to interference from background masking
      noise. These findings highlight the potential to improve the neural and
      perceptual salience of degraded sensory stimuli through immersive computerized
      games. 

PMID- 24927597
TI  - Integration of bacterial lytic polysaccharide monooxygenases into designer
      cellulosomes promotes enhanced cellulose degradation.
AB  - Efficient conversion of cellulose into soluble sugars is a key technological
      bottleneck limiting efficient production of plant-derived biofuels and chemicals.
      In nature, the process is achieved by the action of a wide range of cellulases
      and associated enzymes. In aerobic microrganisms, cellulases are secreted as free
      enzymes. Alternatively, in certain anaerobic microbes, cellulases are assembled
      into large multienzymes complexes, termed "cellulosomes," which allow for
      efficient hydrolysis of cellulose. Recently, it has been shown that enzymes
      classified as lytic polysaccharide monooxygenases (LPMOs) were able to strongly
      enhance the activity of cellulases. However, LPMOs are exclusively found in
      aerobic organisms and, thus, cannot benefit from the advantages offered by the
      cellulosomal system. In this study, we designed several dockerin-fused LPMOs
      based on enzymes from the bacterium Thermobifida fusca. The resulting chimeras
      exhibited activity levels on microcrystalline cellulose similar to that of the
      wild-type enzymes. The dockerin moieties of the chimeras were demonstrated to be
      functional and to specifically bind to their corresponding cohesin partner. The
      chimeric LPMOs were able to self-assemble in designer cellulosomes alongside an
      endo- and an exo-cellulase also converted to the cellulosomal mode. The resulting
      complexes showed a 1.7-fold increase in the release of soluble sugars from
      cellulose, compared with the free enzymes, and a 2.6-fold enhancement compared
      with free cellulases without LPMO enhancement. These results highlight the
      feasibility of the conversion of LPMOs to the cellulosomal mode, and that these
      enzymes can benefit from the proximity effects generated by the cellulosome
      architecture. 

PMID- 24927598
TI  - An iron-regulated and glycosylation-dependent proteasomal degradation pathway for
      the plasma membrane metal transporter ZIP14.
AB  - Protein degradation is instrumental in regulating cellular function. Plasma
      membrane proteins targeted for degradation are internalized and sorted to
      multivesicular bodies, which fuse with lysosomes, where they are degraded. ZIP14
      is a newly identified iron transporter with multitransmembrane domains. In an
      attempt to dissect the molecular mechanisms by which iron regulates ZIP14 levels,
      we found that ZIP14 is endocytosed, extracted from membranes, deglycosylated, and
      degraded by proteasomes. This pathway did not depend on the retrograde
      trafficking to the endoplasmic reticulum and thus did not involve the well
      defined endoplasmic reticulum-associated protein degradation pathway. Iron
      inhibited membrane extraction of internalized ZIP14, resulting in higher steady
      state levels of ZIP14. Asparagine-linked (N-linked) glycosylation of ZIP14,
      particularly the glycosylation at N102, was required for efficient membrane
      extraction of ZIP14 and therefore is necessary for its iron sensitivity. These
      findings highlight the importance of proteasomes in the degradation of
      endocytosed plasma membrane proteins. 

PMID- 24927600
TI  - Compositional landscape for glass formation in metal alloys.
AB  - A high-resolution compositional map of glass-forming ability (GFA) in the Ni-Cr
      Nb-P-B system is experimentally determined along various compositional planes.
      GFA is shown to be a piecewise continuous function formed by intersecting
      compositional subsurfaces, each associated with a nucleation pathway for a
      specific crystalline phase. Within each subsurface, GFA varies exponentially with
      composition, wheres exponential cusps in GFA are observed when crossing from one
      crystallization pathway to another. The overall GFA is shown to peak at multiple
      exponential hypercusps that are interconnected by ridges. At these compositions,
      quenching from the high-temperature melt yields glassy rods with diameters
      exceeding 1 cm, whereas for compositions far from these cusps the critical rod
      diameter drops precipitously and levels off to 1 to 2 mm. The compositional
      landscape of GFA is shown to arise primarily from an interplay between the
      thermodynamics and kinetics of crystal nucleation, or more precisely, from a
      competition between driving force for crystallization and liquid fragility. 

PMID- 24927602
TI  - Predicting outcome in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune liver disease
      that may ultimately result in liver failure and premature death. Predicting
      outcome is of key importance in clinical management and an essential requirement
      for patients counselling and timing of diagnostic and therapeutic interventions.
      The following factors are associated with progressive disease and worse outcome:
      young age at diagnosis, male gender, histological presence of cirrhosis,
      accelerated marked uctopenia in relation to the amount of fibrosis, high serum
      bilirubin, low serum albumin levels, high serum alkaline phosphatase levels,
      esophageal varices, hepatocellular carcinoma (HCC) and lack of biochemical
      response to ursodeoxycholic acid (UDCA). The prognostic significance of symptoms
      at diagnosis is uncertain. UDCA therapy and liver transplantation have a
      significant beneficial effect on the outcome of the disease. The Mayo risk score
      in PBC can be used for estimating individual prognosis. The Newcastle Varices in
      PBC Score may be a useful clinical tool to predict the risk for development of
      esophageal varices. Male gender, cirrhosis and non-response to UDCA therapy in
      particular, are risk factors for development of HCC.

PMID- 24927603
TI  - What is changing in indications and treatment of hepatic hemangiomas. A review.
AB  - Hepatic cavernous hemangioma accounts for 73% of all benign liver tumors with a
      frequency of 0.4-7.3% at autopsy and is the second most common tumor seen in the
      liver after metastases. Patients affected by hemangioma usually have their tumor
      diagnosed by ultrasound abdominal examination for a not well defined pain, but
      pain persist after treatment of the hemangioma. The causes of pain can be various
      gastrointestinal pathologies including cholelithiasis and peptic ulcer
      disease.The malignant trasformation is practically inexistent. Different imaging
      modalities are used to diagnosis liver hemangioma including ultrasonography,
      computed tomography (CT), magnetic resonance (MR) imaging, and less frequently
      scintigraphy, positronemission tomography combined with CT (PET/CT) and
      angiography. Imaging-guided biopsy of hemangioma is usually not resorted to
      except in extremely atypical cases. The right indications for surgery remain
      rupture, intratumoral bleeding, Kasabach-Merritt syndrome and organ or vessels
      compression (gastric outlet obstruction, Budd-Chiari syndrome, etc.) represents
      the valid indication for surgery and at the same time they are all complications
      of the tumor itself. The size of the tumor do not represent a valid indication
      for treatment. Liver hemangiomas, when indication exist, have to be treated
      firstly by surgery (hepatic resection or enucleation, open, laproscopic or
      robotic), but in the recent years other therapies like liver transplantation,
      radiofrequency ablation, radiotherapy, trans-arterial embolization, and
      chemotherapy have been applied. 

PMID- 24927599
TI  - High-throughput comparison, functional annotation, and metabolic modeling of
      plant genomes using the PlantSEED resource.
AB  - The increasing number of sequenced plant genomes is placing new demands on the
      methods applied to analyze, annotate, and model these genomes. Today's annotation
      pipelines result in inconsistent gene assignments that complicate comparative
      analyses and prevent efficient construction of metabolic models. To overcome
      these problems, we have developed the PlantSEED, an integrated, metabolism
      centric database to support subsystems-based annotation and metabolic model
      reconstruction for plant genomes. PlantSEED combines SEED subsystems technology,
      first developed for microbial genomes, with refined protein families and
      biochemical data to assign fully consistent functional annotations to orthologous
      genes, particularly those encoding primary metabolic pathways. Seamless
      integration with its parent, the prokaryotic SEED database, makes PlantSEED a
      unique environment for cross-kingdom comparative analysis of plant and bacterial
      genomes. The consistent annotations imposed by PlantSEED permit rapid
      reconstruction and modeling of primary metabolism for all plant genomes in the
      database. This feature opens the unique possibility of model-based assessment of
      the completeness and accuracy of gene annotation and thus allows computational
      identification of genes and pathways that are restricted to certain genomes or
      need better curation. We demonstrate the PlantSEED system by producing consistent
      annotations for 10 reference genomes. We also produce a functioning metabolic
      model for each genome, gapfilling to identify missing annotations and proposing
      gene candidates for missing annotations. Models are built around an extended
      biomass composition representing the most comprehensive published to date. To our
      knowledge, our models are the first to be published for seven of the genomes
      analyzed. 

PMID- 24927604
TI  - Long term changes in liver histology following treatment of chronic hepatitis C
      virus.
AB  - BACKGROUND AND AIMS: The histologic hallmarks of chronic HCV include inflammation
      and fibrosis. The impact of interferon therapy on liver histology was evaluated.
      MATERIAL AND METHODS: The study population consisted of 348 patients with chronic
      HCV who underwent a baseline liver biopsy, received either no treatment or a
      single course of interferon based therapy, were followed for 5 years without any
      treatment or additional treatment and then underwent a repeat liver biopsy. The
      patients were divided into 3 groups; deferred treatment (NoTx = 47), received
      interferon based therapy but failed to achieve SVR (NoSVR = 189) and achieved SVR
      (SVR = 112). RESULTS: Patients with NoTx and NoSVR had significant increases in
      mean inflammation scores (from 4.3 to 6.3 and 5.4 to 6.7 respectively; p < 0.001
      for both) and fibrosis scores (from 0.9 to 1.8 and 1.9 to 2.5; p < 0.001 for
      both). The amounts by which inflammation, fibrosis and rate of fibrosis
      progression increased were not significantly different between the two groups.
      Increases in total inflammation and the piecemeal necrosis sub-score over time
      were strongly associated with fibrosis progression. Patients with SVR had a
      significant decline in mean inflammation and fibrosis scores (from 6.7 to 2.2 and
      3.3 to 1.8; p < 0.001 for both); 40% of patients resolved all fibrosis and 50% of
      patients resolved cirrhosis. CONCLUSION: Increases in inflammation are associated
      with fibrosis progression and in the absence of SVR interferon treatment does not
      appear to affect the long term natural history of this process. Patients with SVR
      have resolution of inflammation and fibrosis and many resolve cirrhosis.

PMID- 24927605
TI  - Peginterferon alpha-2b plus ribavirin for chronic hepatitis C virus mixed
      genotype infection.
AB  - BACKGROUND AND AIM: The treatment efficacy of peginterferon plus ribavirin for
      patients with HCV genotype 1 is inferior to that in patients with HCV genotype 2,
      but the efficacy among patients with mixed HCV genotype 1 + 2 is less clear. We
      compared the treatment outcome of peginterferon alpha-2b plus ribavirin among
      naive chronic hepatitis C patients in Taiwan with HCV genotype 1 and 2, and mixed
      genotype 1 + 2. MATERIAL AND METHODS: In this retrospective cohort study, 150
      patients were treated with peginterferon alpha-2b once weekly, plus ribavirin,
      for 24 weeks. The endpoint was sustained virological response after receiving at
      least one dose of the study medication. RESULTS: There were no differences in
      clinical characteristics among the 3 groups. There were significant differences
      in rapid virological response rate between patients with genotype 1 and genotype
      2 (64.7 vs. 85.5%, respectively; p < 0.05) and a sustained virological response
      rate (55.9 vs. 83.6%, respectively; p = 0.001). The rapid virological response
      rate differed between the genotype 1 and mixed genotype 1 + 2 groups (64.7 vs.
      85.2%, respectively; p < 0.05), but the sustained virological response rate was
      similar (55.9 vs. 74.1%; p = 0.101). CONCLUSIONS: Using peginterferon alpha-2b
      plus ribavirin for 24 weeks to treat patients with HCV genotype 1 + 2 achieved a
      74.1% sustained virological response rate; the treatment efficacy was not
      inferior to patients with HCV genotype 1, but the percentage of liver cirrhosis
      in mixed genotype 1 + 2 group was higher to 22%, it is worth to be appropriately
      valued and studied.

PMID- 24927606
TI  - PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in
      hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) is associated with a higher prevalence of
      steatosis compared to the general population. AIM: Our aim was to assess the
      impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients. MATERIAL AND
      METHODS: We included 474 HCV patients treated with peginterferon plus ribavirin.
      PNPLA3 rs738409 was genotyped and patients were classified according to alleles
      and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed
      by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using
      Real Time-PCR. RESULTS: PNPLA3 allele-G was associated with steatosis [54.1%
      (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to
      steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3
      [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with
      steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p =
      0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442).
      Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84
      (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017],
      HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72
      (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC
      from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with
      JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 +/- 0.2),
      while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5
      +/- 0.2). CONCLUSION: PNPLA3 allele-G modulated the development of steatosis,
      particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not
      associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3
      regulated. Gene interaction may result in differential PNPLA3 gene expression
      levels in HCV infection.

PMID- 24927607
TI  - A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin
      for chronic HCV.
AB  - OBJECTIVES: Filibuvir is a non-nucleoside inhibitor of hepatitis C virus (HCV)
      polymerase. This study evaluated the safety and efficacy of filibuvir plus
      pegylated interferon alfa-2a (pegIFN)/ribavirin. MATERIAL AND METHODS: Treatment
      naive, HCV genotype-1 patients were randomized to receive filibuvir 300 or 600 mg
      twice daily (BID) or placebo plus pegIFN (180 MUg/wk) and ribavirin (1,000/1,200
      mg BID) for 24 weeks. Filibuvir patients who achieved defined response through
      week 24 discontinued therapy at week 24. All other patients continued on open
      label pegIFN/ribavirin through week 48. The primary endpoint was the proportion
      of patients who achieved sustained virologic response (SVR) defined as HCV RNA <
      15 IU/mL at end of treatment (weeks 24 or 48) and week 72. RESULTS: Overall, 288
      patients were randomized and treated. SVR was achieved by 41.7, 39.6, and 45.8%
      of patients in the filibuvir 300 mg, 600 mg, and placebo arms, respectively.
      While the addition of filibuvir to pegIFN/ribavirin improved on-treatment
      virologic response parameters, this did not translate into improved SVR rates due
      to a high rate of virologic relapse following completion of therapy (300 mg:
      35.9%; 600 mg: 42.9%; placebo: 25.4%). The most commonly reported adverse events
      were nausea, fatigue, headache, and insomnia, and were reported at similar rates
      across arms. CONCLUSIONS: Filibuvir plus pegIFN/ribavirin did not improve the
      percentage of patients achieving SVR compared with administration of
      pegIFN/ribavirin alone. However, the agent was well tolerated and was associated
      with higher on-treatment virologic response parameters. Further evaluation of
      filibuvir in combination with other direct-acting antiviral agents may be
      considered.

PMID- 24927608
TI  - Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B
      HBeAg negative genotype D patients and risk for hepatocellular carcinoma.
AB  - BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide
      (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg
      negative genotype D patients has not been adequately studied in real-life
      cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables
      on HCC incidence in this population of patients. Of 745 patients with chronic
      hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in
      this study. All patients received treatment with NUC for at least 18 months.
      Patients with CHB or compensated cirrhosis were included. Patients with HCC
      diagnosed before or during the first 18 months of NUC therapy were excluded.
      RESULTS: HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients
      (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis
      revealed that HCC risk was independently associated with age >= 60 years (OR =
      6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39
      to 106.2; p = 0.02), but not with virological response (VR), and previous
      resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients
      revealed that only age >= 60 years was an independent risk factor associated with
      HCC (p = 0.003). CONCLUSIONS: Liver cirrhosis and age >= 60 years are the
      stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous
      resistance to NUC in patients that achieved a VR after rescue therapy was not a
      predictive factor regarding HCC. VR does not appear to significantly reduce the
      overall incidence of HCC when a patient has already progressed to liver
      cirrhosis.

PMID- 24927609
TI  - Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort.
AB  - BACKGROUND AND AIM: The lack of information about hepatocellular carcinoma (HCC)
      in Brazil weakens health policy in preventing deaths from the illness. The aim of
      this study was to establish the cumulative incidence and the risk factors for
      hepatocellular carcinoma development in patients under a surveillance program.
      MATERIAL AND METHODS: 884 patients with compensated cirrhosis were prospectively
      followed up for at least five years, from August 1998 until August 2008, with at
      least one annual ultrasonography liver examination and serum alpha fetoprotein
      (AFP) measurement. RESULTS: Among 884 patients, 72 (8.1%) developed a tumor with
      a median follow up of 21.4 months. In the hepatocellular carcinoma group,
      hepatitis C virus infection was the major etiological factor (65.3%), 56.9%
      (41/72) were male and the mean average age was 57 +/- 10 years. The annual
      incidence of hepatocellular carcinoma was 2.9%. 79.2% (57/72) of HCCs were
      detected within Milan Criteria, and the mean survival time was 52.3 months,
      significantly higher than for those outside Milan, with a mean time of 40.6
      months (p = 0.0003). CONCLUSION: The annual incidence of HCC among this large
      series of Brazilian cirrhotic patients was around 2.9% with a detection rate of
      8.1%, or a cumulative incidence rate over five years of 14.3%. The three
      variables related to HCC risk were low serum albumin [HR: 0.518 (0.46-0.78)],
      high AFP > 20 ng/mL [HR: 3.16 (1.86-5.38)], and ethnicity (Brazilian-East Asian
      descendants vs. other mixed Brazilian ethnicities) [HR: 2.86 (1.48-5.53)].

PMID- 24927610
TI  - Preoperative transcatheter arterial chemoembolization for resectable
      hepatocellular carcinoma: a single center analysis.
AB  - BACKGROUND AND AIM: The effect of preoperative transcatheter arterial
      chemoembolization (TACE) on the short- and long-term outcome of resectable
      hepatocellular carcinoma (HCC) is controversial. We conducted a retrospective
      evaluation of this aspect using data from our center. MATERIAL AND METHODS: A
      total of 656 consecutive patients who underwent curative resection of HCC were
      divided into two groups based on the preoperative TACE: the liver resection (LR)
      group (405 cases) and the TACE-LR group (183 cases). Overall and disease-free
      survival curves were constructed using the Kaplan-Meier method and compared with
      the log-rank test. The significance of differences in survival was tested using a
      log-rank test. Univariate and multivariate analyses were used to identify the
      factors that best predicted overall survival or tumor free survival. RESULTS:
      Although the cost of LR showed no difference between groups, the overall cost was
      significantly higher in the combined group than in the LR group (P < 0.001). The
      complication rate after resection was also comparable between the two groups. In
      regard to long-term outcome, the 1-, 3-, and 5-year overall survival rates were
      83.7, 68.9 and 57.5%, respectively, after direct liver resection and 80.9, 65.0
      and 54.1%, respectively, after combined TACE and resection (P = 0.739). The 1-, 3
      , and 5-year recurrence- free survival rates were also comparable between two
      groups (P = 0.205). Both univariate analysis and multivariate analysis showed
      that macro-vascular invasion was the factor that best predicted overall survival
      or tumor-free survival rate. CONCLUSION: Preoperative TACE has comparable
      intraoperative and short-term outcomes but more overall cost due to repeated
      TACE, and the procedure did not significantly improve the overall or tumor-free
      survival rate. Preoperative TACE should not, therefore, be recommended as a
      routine procedure before resection for resectable HCCs particularly in cases due
      to underlying hepatitis B virus (HBV).

PMID- 24927611
TI  - Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose
      tolerance and diabetes mellitus. A prospective study.
AB  - AIMS: To define if there is an imbalance in plasma levels of proinflammatory,
      fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and
      impaired glucose tolerance (IGT) or diabetes mellitus (DM). MATERIAL AND METHODS:
      We randomly selected 54 out of 100 patients with LC who had normal fasting plasma
      glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance
      test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma
      levels of cytokines were measured: TNF- alpha, soluble tumor necrosis factor
      receptor 1 (sTNF-R1), leptin, TGF-beta1, and hepatocyte growth factor (HGF).
      Also, fasting plasma insulin (FPI) levels were determined and HOMA2-IR was
      calculated. Results were compared with those of a control group of 18 patients
      without liver disease nor DM. Intergroup comparison was performed using non
      parametric tests. RESULTS: Significantly higher sTNF-R1 and lower TGF-beta1 were
      found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF
      alpha levels showed no significant differences. According to Child-Pugh
      classification all cytokines levels were impaired in groups B or C as compared to
      group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin
      and HOMA2-IR were found. CONCLUSIONS: IGT and DM were associated with
      abnormalities of sTNF-R1 and TGF-beta1 compared to non cirrhotic controls. Among
      cirrhotic patients impairment of all cytokines were more marked in advanced liver
      disease. Finally, sTNF-R1 and leptin correlated with IR. These findings suggest
      that IGT and DM may be causally implicated with liver inflammation process.

PMID- 24927612
TI  - Right atrial pressure may impact early survival of patients undergoing
      transjugular intrahepatic portosystemic shunt creation.
AB  - PURPOSE: To elucidate the impact of right atrial (RA) pressure on early mortality
      after transjugular intrahepatic portosystemic shunt (TIPS). MATERIAL AND METHODS:
      In this single institution retrospective study, 125 patients (M:F = 75:50, mean
      age 55 years) who underwent TIPS with recorded intra-procedural RA pressures
      between 1999-2012 were studied. Demographic (age, gender), liver disease (Child
      Pugh, Model for End Stage Liver Disease or MELD score), and procedure
      (indication, urgency, Stent type, portosystemic gradient or PSG reduction,
      baseline and post-TIPS RA pressure) data were identified, and the influence of
      these parameters on 30- and 90-day mortality was assessed using binary logistic
      regression. RESULTS: TIPS were created for variceal hemorrhage (n = 55) and
      ascites (n = 70). Hemodynamic success rate was 99% (124/125) and mean PSG
      reduction was 13 mmHg. 30- and 90-day mortality rates were 18% (19/106) and 28%
      (29/106). Baseline and final RA pressure were significantly associated with 30-
      (12 vs. 15 mmHg, P = 0.021; 18 vs. 21 mmHg, P = 0.035) and 90-day (12 vs. 14
      mmHg, P = 0.022; 18 vs. 20 mmHg, P = 0.024) survival on univariate analysis.
      Predictive usefulness of RA pressure was not confirmed in multivariate analyses.
      Area under receiver operator characteristic (AUROC) curve analysis revealed good
      pre- and post-TIPS RA pressure predictive capacity for 30- (0.779, 0.810) and 90
      day (0.813, 0.788) mortality among variceal hemorrhage patients at 14.5 and 21.5
      mm Hg thresholds. CONCLUSION: Intra-procedural RA pressure may have predictive
      value for early post-TIPS mortality. Pre-procedure consideration and optimization
      of patient cardiac status may enhance candidate selection, risk stratification,
      and clinical outcomes, particularly in variceal hemorrhage patients.

PMID- 24927613
TI  - Hemodynamic effect of carvedilol vs. propranolol in cirrhotic patients:
      Systematic review and meta-analysis.
AB  - BACKGROUND: Carvedilol appears to be more effective than propranolol in the
      treatment of portal hypertension in cirrhotic patients. Aim. To compare the
      effects of carvedilol vs. propranolol on systemic and splanchnic haemodynamics
      and to evaluate the adverse events associated with these treatments. MATERIAL AND
      METHODS: We performed a systematic review following the Cochrane and PRISMA
      recommendations. Randomised controlled trials comparing carvedilol versus
      propranolol, in the treatment of portal hypertension in cirrhotic patients with
      oesophageal varices, with or without bleeding history were included. The primary
      outcome measure was the haemodynamic response to treatment. RESULTS: Four
      randomised trials and 153 patients were included; 79 patients received carvedilol
      (6.25-50 mg/d) and 74 patients received propranolol (10-320 mg/d). The hepatic
      vein pressure gradient (HVPG) decreased more with carvedilol than with
      propranolol (MD -2.21; 95% CI: -2.83 to -1.60, I(2) = 0%, P < 0.00001).
      Carvedilol was superior to propranolol for reducing HVPG by >= 20% from the
      baseline value or to <= 12 mmHg (OR: 2.93; 95% CI: 1.50 to 5.74, I(2) = 22%, P =
      0.002). Overall adverse events did not differ between. In conclusion, there is
      limited evidence suggesting that carvedilol is more effective than propranolol
      for improving the haemodynamic response in cirrhotic patients with portal
      hypertension. Long-term randomized controlled trials are needed to confirm this
      information.

PMID- 24927614
TI  - Adult human liver contains intermediate-type proteasomes with different enzymatic
      properties.
AB  - BACKGROUND: The 20S proteasome is the proteolytic core of the major intracellular
      protein degradative system, the ubiquitin-proteasome system. Since little is
      known about proteasomes of human liver, we have investigated the proteasome
      spectrum in adult human liver. MATERIAL AND METHODS: 20S proteasomes were
      chromatographically purified from adult human liver and from HuH7 cells. They
      were divided into subpopulations and subtypes and characterized with regard to
      their proteolytic activities using short fluorogenic oligo- and long poly-peptide
      substrates. Their subunit composition was studied by immunoblotting. RESULTS:
      Proteasomes from adult human liver tissue can be separated into three
      subpopulations (I, II, III), each of which is composed of several subtypes, which
      total to a spectrum of 14 different subtypes. Two minor subtypes contain only the
      immuno-subunits beta1i and beta5i but not their standard counterparts; all others
      are intermediate subtypes containing beta1 and beta5 standard- and beta1i and
      beta5i immuno-subunits in various compositions. With regard to the proteolytic
      activities we observed that a decreasing content of subunit beta1i in the
      subtypes goes along with a decreasing ratio of chymotrypsin-like/caspase-like
      activity, whereas the degradation rate of a 30 mer polypeptide substrate
      increased with decreasing beta1i content. By comparison, 20S proteasomes from
      HuH7 cells do not contain immuno-subunits but are pure standard proteasomes,
      which can be separated into three subtypes. CONCLUSION: These findings suggest
      that adult human liver contains a spectrum of 14 different 20S proteasome
      subtypes with different enzymatic properties reflecting most probably an adaptive
      response of liver cell functions to challenging factors during lifetime.

PMID- 24927615
TI  - Deep sequencing analysis of microRNA expression in porcine serum-induced hepatic
      fibrosis rats.
AB  - AIM: Recent studies have suggested miRNA dysregulation in liver tissue mediates
      the pathogenesis of various liver diseases especially liver fibrosis, but the
      microRNA changes during PS-induced hepatic fibrosis are still unknown. The
      purpose of this study was to screen the miRNA differences in rat liver fibrosis
      model and clarify the relationship of miRNAs with the development of PS-induced
      liver fibrosis. MATERIAL AND METHODS: Two fibrotic and two normal liver tissues
      from 20 Sprague-Dawley rats were collected and sequenced. MiRNA profiling results
      and fibrosis-related genes were validated by quantitative real-time polymerase
      chain reaction (qRT-PCR) and bioinformatics was used to predict miRNA targets.
      RESULTS: In total, 48 miRNAs were detected to be aberrantly expressed in fibrosis
      tissue compared to normal tissue. Further functional analysis of the deregulated
      miRNA targets revealed the miRNAs are involved in several biological functions
      and pathways. In addition, the expression level of miR-27a and miR-146b and
      fibrosis-related genes were significantly up-regulated by using qRT-PCR in
      fibrotic liver tissues when compared to the normal liver tissues. CONCLUSION: PS
      induced hepatic fibrosis results in up-regulation of the miR-27a and miR-146b in
      liver tissues, suggestingmiR-27a and miR-146b would be associated with the
      development of PS-induced liver fibrosis and be potential therapeutic targets
      during hepatic fibrosis.

PMID- 24927616
TI  - Hepatocellular adenoma: different entities for a single lesion.

PMID- 24927617
TI  - Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir
      and simvastatin.
AB  - A 46-year old man with a chronic hepatitis C virus infection received triple
      therapy with ribavirin, pegylated interferon and telaprevir. The patient also
      received simvastatin. One month after starting the antiviral therapy, the patient
      was admitted to the hospital because he developed rhabdomyolysis. At admission
      simvastatin and all antiviral drugs were discontinued because toxicity due to a
      drug-drug interaction was suspected. The creatine kinase peaked at 62,246 IU/L
      and the patient was treated with intravenous normal saline. The patient's renal
      function remained unaffected. Fourteen days after hospitalization, creatine
      kinase level had returned to 230 IU/L and the patient was discharged. Telaprevir
      was considered the probable causative agent of an interaction with simvastatin
      according to the Drug Interaction Probability Scale. The interaction is due to
      inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin plasma
      concentration increased 30 times in this patient and statin induced muscle
      toxicity is related to the concentration of the statin in blood. In conclusion,
      with this case we illustrate that telaprevir as well as statins are susceptible
      to clinical relevant drug-drug interactions.

PMID- 24927618
TI  - Persistent hepatic encephalopathy secondary to portosystemic shunt occluded with
      Amplatzer device.
AB  - Hepatic encephalopathy is a frequent complication of cirrhosis, when this event
      becomes persistent, treatment compliance should be verified and any precipitating
      factor need to be identified. Also the presence of portosystemic shunts, which
      are a rare cause of decompensation or persistence hepatic encephalopathy need to
      be ruled out. In this paper we report the case of a 57 year old man with
      persistent hepatic encephalopathy secondary to the presence of a porto-onfalo
      femoral shunt successfully closed with the placement of an Amplatzer device.

PMID- 24927619
TI  - Hepatitis B reactivation in patients with multiple myeloma and isolated positive
      hepatitis B core antibody: a call for greater cognizance.
AB  - Hepatitis B virus (HBV) reactivation is a well-established complication of severe
      immunosuppression in patients with hematologic malignancy and positive hepatitis
      B surface antigen (HBsAg). Patients who receive high-dose chemotherapy,
      corticosteroids, rituximab, or have a bone marrow transplant are particularly at
      increased risk for HBV reactivation. However, limited information is available in
      the literature regarding HBV reactivation in patients with isolated anti-HBc,
      particularly in the setting of multiple myeloma (MM). We report two cases of HBV
      reactivation in MM patients with isolated anti-HBc positive with a rather
      atypical presentation. In conclusion, our cases highlight that clinicians need to
      be cognizant about this potentially fatal but preventable complication of
      chemotherapy and immunosuppression.

PMID- 24927620
TI  - Severe aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome in a patient
      with non-A-E hepatitis virus infection.

PMID- 24927621
TI  - Hepatopulmonary syndrome: Is it time to redefine the MELD exception score for
      better organ allocation and outcomes?

PMID- 24927623
TI  - Ionization of acids on the quasi-liquid layer of ice.
AB  - The ice quasi-liquid layer (QLL) forms on ice surfaces below the bulk ice melting
      temperature. It is abundant in the atmosphere, and its importance for atmospheric
      chemistry is recognized. In the present work, we have studied the microscopic
      mechanisms of acid ionization on the QLL using ab initio molecular dynamics. The
      model system QLL is established by nanosecond time scale simulations with
      empirical force fields, while the reactivity of the QLL is studied using ab
      initio molecular dynamics. Our ab initio simulations reveal that QLL is reactive,
      exhibiting stable crystalline point defects, which contribute to efficient acid
      solvation, ionization, and proton transfer. We study in detail deuterated
      hydrogen iodide (DI) and nitric acid (DNO3). Ionization in both cases benefits
      from the abundance of weakly bonded hydrogen-bond single-acceptor double-donor
      water molecular species available on the QLL in high relative concentration.
      Picosecond time scale ionization is demonstrated for both molecular species. Our
      results suggest efficient reactivity of acid ionization and proton transfer at
      temperature ranges appropriate for the upper troposphere and lower stratosphere. 

PMID- 24927622
TI  - Estimating the optimal threshold for a diagnostic biomarker in case of complex
      biomarker distributions.
AB  - BACKGROUND: Estimating the optimal threshold (and especially the confidence
      interval) of a quantitative biomarker to be used as a diagnostic test is
      essential for medical decision-making. This is often done with simple methods
      that are not always reliable. More advanced methods work well but only for
      biomarkers with very simple distributions. In fact, biomarker distributions are
      often complex because of a natural heterogeneity in marker expression and other
      heterogeneities due to various disease stages, laboratory equipments, etc.
      Methods are required to estimate a biomarker optimal threshold in case of
      heterogeneity and complex distributions. METHODS: A previously described Bayesian
      method developed for normally distributed biomarkers is applied to two flexible
      distributions; namely, a Student-t and a mixture of Dirichlet processes. Here,
      numerical studies assess the adequacy of the previous method with both
      distributions. Two applications are presented: the diagnosis of treatment failure
      after prostate cancer treated by ultrasound and the early diagnosis of cancers of
      the upper aerodigestive tract. RESULTS: Bayesian inference provided reliable
      credible intervals in terms of bias and coverage probability. The two
      distributions analysed gave meaningful clinical interpretations in both
      applications. CONCLUSIONS: Reliable methods can be used to estimate a biomarker
      optimal threshold, even in case of complex distributions.

PMID- 24927624
TI  - Outcome of proximal femoral fractures caused by cycling in the young and mid
      aged.
AB  - BACKGROUND: Cycling is gaining more popularity both as a sport, on and off-road
      and also as a means of commute. Cycling accidents harbour significant injury
      risks including fractures. Proximal femoral fractures are uncommonly associated
      with cycling in the young adult population. The purpose of this study is to
      describe this unique pattern of injury as well as the outcome of proximal femoral
      fractures caused by cycling in the young to mid age population. METHODS:  STUDY
      DESIGN: retrospective cohort study. 23 fractures in 22 patients were available
      for analysis. 11 were femoral neck fractures, with six displaced ones, and the
      rest trochanteric fractures. 21 patients were male patients, and the average age
      was 42 (range 27-60). All patients but two were operated within 24 h from
      admission. Radiographic analysis included reduction quality, fracture
      classification and arthritic changes. Clinical outcome was measured using SF-12
      and Oxford hip scores. RESULTS: All fractures healed. Two patients with displaced
      femoral neck fractures developed avascular necrosis requiring arthroplasty. One
      patient developed an AVN 2 years after a stable trochanteric fracture but did not
      require an arthroplasty as of yet. Eight patients required hardware removal due
      to symptoms. 77% of patients had resumed cycling at the pre-injury level. Mean SF
      12 score was 47.1 +/- 11.7 for the physical component and 53.7 +/- 6.3 for the
      mental component. Mean oxford hip score as was 40.1 +/- 12.2. Radiographic
      analysis revealed good to acceptable reduction quality. Fracture type, age,
      cycling type and reduction were not significantly associated with outcome.
      CONCLUSION: Proximal femoral fractures caused by cycling in young to mid-aged
      adults are an emerging pattern of injury. Overall favourable result can be
      expected in the majority of cases, with displaced femoral neck fractures having a
      risk for AVN. Further delineation of the exact cause for this phenomenon is
      required with possible intervention for injury prevention.

PMID- 24927625
TI  - A new technique for stabilization of injuries at C2-C3 in young children.
AB  - BACKGROUND: Reported surgical treatment for injuries and instabilities of the
      paediatric cervical spine most commonly involves posterior fusion with internal
      fixation, usually posterior wiring. PURPOSE: To present a new simple technique of
      stabilization without fusion of the upper cervical spine of young children. STUDY
      DESIGN: A technical report. METHODS: Detailed description of the surgical
      procedure carried out for stabilizing an unstable flexion-distraction injury in a
      23 month-old toddler, with severe head injury and pneumothorax is presented.
      RESULTS: A rare unstable flexion-distraction injury in the upper cervical spine
      of a toddler was successfully treated with a posterior Number 2 Vicryl
      (polyglactin 910) suture fixation, with good healing of the ligaments and
      endplates, without fusion. Preservation of motion was achieved without obvious
      instability at 63 months post-surgery. CONCLUSIONS: In selected cases of cervical
      spine injuries in the young paediatric population, a limited approach to the
      injured spinal segments and simple stabilization using suitable degradable
      sutures, can provide sufficient stability until healing occurs. ADVANTAGES:
      fusion is avoided, growth disturbances are prevented and spinal motion
      maintained.

PMID- 24927626
TI  - Trade as a structural driver of dietary risk factors for noncommunicable diseases
      in the Pacific: an analysis of household income and expenditure survey data.
AB  - BACKGROUND: Noncommunicable diseases are a health and development challenge.
      Pacific Island countries are heavily affected by NCDs, with diabetes and obesity
      rates among the highest in the world. Trade is one of multiple structural drivers
      of NCDs in the Pacific, but country-level data linking trade, diets and NCD risk
      factors are scarce. We attempted to illustrate these links in five countries. The
      study had three objectives: generate cross-country profiles of food consumption
      and expenditure patterns; highlight the main 'unhealthy' food imports in each
      country to inform targeted policymaking; and demonstrate the potential of HCES
      data to analyze links between trade, diets and NCD risk factors, such as obesity.
      METHODS: We used two types of data: obesity rates as reported by WHO and
      aggregated household-level food expenditure and consumption from Household Income
      and Expenditure Survey reports. We classified foods in HIES data into four
      categories: imported/local, 'unhealthy'/'healthy', nontraditional/traditional,
      processed/unprocessed. We generated cross-country profiles and cross-country
      regressions to examine the relationships between imported foods and unhealthy
      foods, and between imported foods and obesity. RESULTS: Expenditure on imported
      foods was considerable in all countries but varied across countries, with highest
      values in Kiribati (53%) and Tonga (52%) and lowest values in Solomon Islands and
      Vanuatu (30%). Rice and sugar accounted for significant amounts of imported foods
      in terms of expenditure and calories, ranking among the top 3 foods in most
      countries. We found significant or near-significant associations in expenditure
      and caloric intake between 'unhealthy' and imported foods as well as between
      imported foods and obesity, though inferences based on these associations should
      be made carefully due to data constraints. CONCLUSIONS: While additional research
      is needed, this study supports previous findings on trade as a structural driver
      of NCD risk and identifies the top imported foods that could serve as policy
      targets. Moreover, this analysis is proof-of-concept that the methodology is a
      cost-effective way for countries to use existing data to generate policy-relevant
      evidence on links between trade and NCDs. We believe that the methodology is
      replicable to other countries globally. A user-friendly Excel tool is available
      upon request to assist such analyses.

PMID- 24927627
TI  - Ultrastructure of the lung in a murine model of malaria-associated acute lung
      injury/acute respiratory distress syndrome.
AB  - BACKGROUND: The mechanisms through which infection with Plasmodium spp. result in
      lung disease are largely unknown. Recently a number of mouse models have been
      developed to research malaria-associated lung injury but no detailed
      ultrastructure studies of the disease in its terminal stages in a murine model
      have yet been published. The goal was to perform an ultrastructural analysis of
      the lungs of mice that died with malaria-associated acute lung injury/acute
      respiratory distress syndrome to better determine the relevancy of the murine
      models and investigate the mechanism of disease. METHODS: DBA/2 mice were
      infected with Plasmodium berghei strain ANKA. Mice had their lungs removed
      immediately after death, processed using standard methods and viewed by
      transmission electron microscopy (TEM). RESULTS: Infected red blood
      cell:endothelium contact, swollen endothelium with distended cytoplasmic
      extensions and thickening of endothelium basement membrane were observed. Septa
      were thick and filled with congested capillaries and leukocytes and the alveolar
      spaces contained blood cells, oedema and cell debris. CONCLUSION: Results show
      that the lung ultrastructure of P. berghei ANKA-infected mice has similar
      features to what has been described in post-mortem TEM studies of lungs from
      individuals infected with Plasmodium falciparum. These data support the use of
      murine models to study malaria-associated acute lung injury.

PMID- 24927628
TI  - Psychosocial work environment, job mobility and gender differences in turnover
      behaviour: a prospective study among the Swedish general population.
AB  - BACKGROUND: Throughout the literature, substantial evidence supports associations
      between poor psychosocial work characteristics and a variety of ill-health
      outcomes. Yet, few reports strategies workers carry out to improve detrimental
      work conditions and consequently their health, such as changing jobs. The aim of
      this study was to examine if adverse psychosocial work exposure, as measured with
      the job demand-control and effort-reward imbalance models, could predict job
      mobility over a 5 years observation period. METHOD: Participants were working men
      and women (n = 940; 54.3% women), aged 24-60 years from the population of
      Gothenburg and surrounding metropolitan area. Job demand-control and effort
      reward variables were compared with independent t-tests and chi2-test in persons
      with and without job mobility. Multivariate logistic regression was used to
      analyse whether psychosocial factors could predict job mobility. All regression
      analyses were stratified by gender. RESULTS: Exposure to a combination of high
      demands-low control or high imbalance between effort and reward was related to
      increased odds of changing jobs (OR 1.63; CI 1.03-2.59 and OR 1.46; CI 1.13-1.89
      respectively). When analysing men and women separately, men had a higher OR of
      changing jobs when exposed to either high demands-low control (OR 2.72; CI 1.24
      5.98) or high effort-reward imbalance (OR 1.74; CI 1.11-2.72) compared to
      reference values. The only significant associations for women was slightly
      decreased odds for turnover in high reward jobs (OR 0.96; CI 0.92-0.99).
      CONCLUSIONS: The results indicate that workers will seek to improve poor work
      environment by changing jobs. There were notable gender differences, where men
      tended to engage in job mobility when exposed to adverse psychosocial factors,
      while women did not. The lack of measures for mechanisms driving job mobility was
      a limitation of this study, thus preventing conclusions regarding psychosocial
      factors as the primary source for job mobility.

PMID- 24927629
TI  - Potato chips and childhood: what does the science say? An unrecognized threat?
AB  - With recent rapid progress in technology and advancing lifestyle associated with
      modernization, individuals are consuming increasing quantities of unhealthy food,
      a major risk factor for the onset of a variety of diseases. In particular, fried
      potato chips (FPCs), are the most commonly consumed snack, especially by
      children. However, research in the field of nutrition demonstrated that FPCs
      encompass significant quantities of acrylamide, a known carcinogen and
      neurotoxin. Thus, frequent intake of FPC, especially at younger age, might
      generate cumulative amounts of acrylamide in the body, thereby silently
      increasing the risk for various diseases. Although intake of a balanced diet can
      prevent this scenario, further measures should be set to overcome the oxidative
      damage from fried food. This review outlines existing scientific evidence
      suggesting an urgent need for systematic study regarding the health effects of
      consumption of FPC and French fries in the general population. 

PMID- 24927630
TI  - Refractory hypoglycemia and subsequent cardiogenic shock in starvation and
      refeeding: report of three cases.
AB  - OBJECTIVE: Although starvation is associated with high in-hospital mortality, its
      related cardiac complications are not sufficiently understood. The aim of this
      study was to determine the clinical course and pathogenesis of cardiac
      complications in malnourished patients. METHODS: We reviewed three cases of
      hypoglycemia and hypotriglyceridemia with cardiac complications in starvation.
      RESULTS: This report concerns three patients, respectively suffering from
      anorexia nervosa, esophageal carcinoma, and Parkinson's disease. Their ages
      ranged from 18 to 70 y, body mass index was 11.5 +/- 1.5 kg/m2 (mean +/- SD), and
      the main symptom was coma. The average blood glucose level was 15.7 +/- 7.8 mg/dL
      without any history of insulin use or diabetes mellitus. In all cases,
      hypoglycemia was refractory and repetitive so that continuous glucose
      administration was required to maintain euglycemia. Serum triglyceride and non
      esterified fatty acid levels were also very low (7 +/- 4 mg/dL and 10 +/- 9.1
      MUEq/L, respectively). Levels of serum potassium, phosphate, and magnesium were
      almost normal at admission. The main cardiac complications included Takotsubo
      cardiomyopathy and cardiac arrest. All patients survived as a result of intensive
      treatment. CONCLUSIONS: Repetitive severe hypoglycemia without known background
      causes should be viewed as an important sign. Once this occurs, the
      administration of a much higher caloric input than usual accompanied by intensive
      monitoring will be required to maintain appropriate glucose levels. The early
      identification of such patients seems to be essential to reduce the high risk for
      cardiac complications during starvation and refeeding.

PMID- 24927632
TI  - [Severe lactic acidosis revealing hematologic malignancy].
AB  - A 75-year-old woman is hospitalised for sepsis. The diagnosis of cholecystitis is
      made and an antibiotic therapy is debuted. The clinical worsening leads to
      realise an urgent cholecystectomy. A sepsis like shock persisted. The
      antibiotherapy was changed and a second abdominal look made. A severe lactic
      acidosis persisted since the cholecystectomy despite a continuous hemofiltration.
      The diagnosis of type B lactic acidosis secondary to malignancy was suspected. An
      osteomedullar biopsy revelled B-cell lymphoma EBV induced. 

PMID- 24927631
TI  - Mechanisms of acquired resistance to androgen receptor targeting drugs in
      castration-resistant prostate cancer.
AB  - After initial response to androgen receptor (AR) targeting drugs abiraterone or
      enzalutamide, most patients develop progressive disease and therefore, castration
      resistant prostate cancer remains a terminal disease. Multiple mechanisms
      underlying acquired resistance have been postulated. Intratumoral androgen
      synthesis may resume after abiraterone treatment. A point mutation in the ligand
      binding domain of AR may confer resistance to enzalutamide. Emergence of AR
      splice variants lacking the ligand-binding domain may mediate resistance to
      abiraterone and enzalutamide. Steroid receptors such as glucocorticoid receptor
      may substitute for AR. Drugs with novel mechanisms of action or combination
      therapy, along with biomarkers for patient selection, may be needed to improve
      the therapy of castration resistant prostate cancer. 

PMID- 24927633
TI  - Upregulation of heme oxygenase-1 in colorectal cancer patients with increased
      circulation carbon monoxide levels, potentially affects chemotherapeutic
      sensitivity.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) and its major product carbon monoxide (CO)
      are known to be involved in the development and progression of many tumors. The
      present study was to elucidate the expression and function of HO-1 in colorectal
      cancer (CRC), specially focusing on the circulation CO levels in CRC patients and
      the possible roles of HO-1 in chemoresistance of colon cancer cells. METHODS: One
      hundred and eighteen patients received resection for colorectal cancer and polyps
      at China Medical University Sheng Jing Hospital, were collected in this study. HO
      1 expression in CRC tissues was analyzed by immnuohistochemical staining;
      circulation CO levels as carboxyhemoglobin (COHb) in CRC patients were analyzed
      by an ABL800 FLEX blood gas analyzer. HO-1 expression in murine colon cells C26
      and human colon cancer cells HT29 and DLD1 under HO-1 inducer hemin and
      anticancer drug pirarubicin (THP) treatment was examined by RT-PCR, and the cell
      viability after each treatment was investigated by MTT assay. Data were analyzed
      by student's t-test or one-way ANOVA followed by Bonferroni t-test or Fisher's
      exact test. RESULTS: HO-1 expression in tumor tissues of CRC (61.0%) was
      significantly higher than in normal colorectal tissues and polyps tissues (29.7%,
      P < 0.01); well-differentiated CRC seemed to express more HO-1 (81.5%) than
      moderately/poorly-differentiated cancers (59.5%, P < 0.05). However, the nuclear
      HO-1 expression is apparently higher in moderately/poorly differentiated CRC than
      well-differentiated CRC probably suggesting a new mechanism of function involved
      in HO-1 in cancer. In parallel with HO-1 expression, circulation CO levels in CRC
      patients also significantly accelerated. Moreover, HO-1 expression/induction also
      related to the chemosensitivity of colon cells; HO inhibitor zinc protoporphyrin
      significantly increased cytotoxicities of THP (i.e., 2.6 - 5.3 folds compared to
      cells without zinc protoporphyrin treatment). CONCLUSIONS: These findings
      strongly suggested HO-1/COHb is a useful diagnostic and prognostic indicator for
      CRC, and inhibition of HO-1 may be a option to enhance the chemotherapeutic
      effects of conventional anticancer drugs toward CRC.

PMID- 24927634
TI  - Breastfeeding and sucking habits in children enrolled in a mother-child health
      program.
AB  - BACKGROUND: Early weaning can cause changes in posture and strength of the
      phonoarticulatory organs, favoring the installation of undesirable oral habits.
      The objective of the research was to evaluate the relationship between the
      practice of exclusive breastfeeding and its influence on the development of
      deleterious oral habits in children. This was a cross sectional observational
      study with 252 children of both sexes, between 30 and 48 months of age, attending
      a program of dental care for mothers and newborns. As an instrument of data
      collection was a questionnaire semistructured mothers of children with questions
      about the form and duration of breastfeeding and non-nutritive oral habits in
      children. RESULTS: In this sample, 48.4% of the children were exclusively
      breastfed for six months; 20.2% exhibited sucking habits involving the use of a
      pacifier, which was more frequent among the girls. As factors associated with the
      decreasing of the occurrence of non-nutritive sucking habits, are a longer
      exclusive breastfeeding, predominant breastfeeding and breastfeeding. Children
      who were breastfed for six months until twelve months in an exclusive way
      decreased by 69.0% chances of coming to have non-nutritive sucking habits when
      compared with those who were breastfed up to one month. CONCLUSION: The longer
      the duration of breastfeeding, that is, exclusive, predominant or breastfeeding,
      the lower are the chances of children develop non-nutritive sucking habits.

PMID- 24927636
TI  - Prevalence, determinants, and management of chronic kidney disease in Karachi,
      Pakistan - a community based cross-sectional study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasing being recognized as a
      global public health problem. However, there is dearth of information on the
      prevalence, determinants, and management of CKD from low- and middle-income
      countries. The objectives of the study were to determine the 1) prevalence of
      CKD; 2) socio-demographic and clinical factors associated with CKD; and 3) the
      existing management of these patients with regards to blood pressure control, and
      use of antihypertensive medications. METHODS: We conducted a cross-sectional
      study on 2873 participants aged >= 40 years in 12 representative communities in
      Karachi, Pakistan. The primary outcome was clinically significant CKD defined as
      estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 estimated by CKD
      EPI (CKD Epidemiology Collaboration) Pakistan equation (0.686 * CKD-EPI1.059) or
      urinary albumin to creatinine ratio >= 3 mg/mmol (i.e. KDOQI CKD stage G3, A2 or
      worse). RESULTS: The overall prevalence (95% CI) of CKD was 12.5% (11.4 - 13.8%).
      The factors independently associated with CKD were older age, hypertension,
      diabetes, elevated systolic blood pressure, raised fasting plasma glucose, raised
      triglycerides, and history of stroke (p<0.05 for each). About 267 (74.4%, 69.5 -
      78.8%) adults with CKD had concomitant hypertension. Of these, 130 (48.7%, 42.6 -
      54.9%) were on antihypertensive medications, and less than 20% had their BP
      controlled to conventional target of <= 140/90 mm Hg, and only 16.9% (12.6 -
      21.9%) were on blockers of renin-angiotensin system alone or in combination with
      other drugs. CONCLUSIONS: Clinically significant CKD is common among Pakistani
      adults. The conventional risk factors for CKD and poor control of blood pressure
      among patients with CKD highlight the need to integrate CKD prevention and
      management in the primary care infrastructure in Pakistan, and possibly
      neighbouring countries.

PMID- 24927635
TI  - Pathognomonic oral profile of Enamel Renal Syndrome (ERS) caused by recessive
      FAM20A mutations.
AB  - Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group
      of inherited dental enamel defects. Commonly described as an isolated trait, it
      may be observed concomitantly with other orodental and/or systemic features such
      as nephrocalcinosis in Enamel Renal Syndrome (ERS, MIM#204690), or gingival
      hyperplasia in Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome (AIGFS,
      MIM#614253). Patients affected by ERS/AIGFS present a distinctive orodental
      phenotype consisting of generalized hypoplastic AI affecting both the primary and
      permanent dentition, delayed tooth eruption, pulp stones, hyperplastic dental
      follicles, and gingival hyperplasia with variable severity and calcified nodules.
      Renal exam reveals a nephrocalcinosis which is asymptomatic in children affected
      by ERS. FAM20A recessive mutations are responsible for both syndromes. We suggest
      that AIGFS and ERS are in fact descriptions of the same syndrome, but that the
      kidney phenotype has not always been investigated fully in AIGFS. The aim of this
      review is to highlight the distinctive and specific orodental features of
      patients with recessive mutations in FAM20A. We propose ERS to be the preferred
      term for all the phenotypes arising from recessive FAM20A mutations. A
      differential diagnosis has to be made with other forms of AI, isolated or
      syndromic, where only a subset of the clinical signs may be shared. When ERS is
      suspected, the patient should be assessed by a dentist, nephrologist and clinical
      geneticist. Confirmed cases require long-term follow-up. Management of the
      orodental aspects can be extremely challenging and requires the input of multi
      disciplinary specialized dental team, especially when there are multiple
      unerupted teeth.

PMID- 24927637
TI  - Methotrexate-associated lymphoproliferative disorders of the tongue developing in
      patients with rheumatoid arthritis: a report of 2 cases and a review.
AB  - Incidences of lymphoproliferative disorders (LPDs) in patients with compromised
      immune systems associated with immunosuppressants such as methotrexate (MTX)
      administered for the treatment of rheumatoid arthritis (RA) are reportedly
      increasing. Although extranodal lesions develop in half of the patients with MTX
      associated LPDs, only a few studies have reported on intraoral lesions. We
      evaluated 2 elderly women with MTX-associated LPDs who had received MTX for the
      treatment of RA and presented with atypical ulceration of the tongue. Biopsy
      specimens demonstrated polymorphous B-cell LPD, probably associated with MTX.
      Epstein-Barr virus (EBV) was identified by immunohistochemistry for latent
      membrane protein 1 and by EBV-encoded RNA in situ hybridization. After MTX
      withdrawal, in both cases, ulcers showed complete regression at 8 weeks, and no
      subsequent treatment was required. Close monitoring of LPDs is mandatory, because
      recurrence within 10 months has been reported in half of the patients in whom
      LPDs had initially regressed. 

PMID- 24927638
TI  - Glucose and glutamine metabolism in oral squamous cell carcinoma: insight from a
      quantitative metabolomic approach.
AB  - OBJECTIVE: To characterize the metabolic system of oral squamous cell carcinoma
      (OSCC) by metabolome analysis. STUDY DESIGN: The metabolome profiles, including
      the Embden-Meyerhof-Parnas pathway (EMPP), the pentose phosphate pathway, the
      tricarboxylic acid cycle (TCAC), and amino acids, were obtained from OSCC and its
      surrounding normal tissues (32 patients) using capillary electrophoresis and a
      time-of-flight mass spectrometer. RESULTS: Enhancement of glucose consumption and
      lactate production (Warburg effect) was observed in OSCC tissues. The decrease of
      glucose along with the decrease of the downstream intermediates in the EMPP
      suggests that incorporated glucose is mainly consumed for biosynthesis. Glutamine
      consumption with the increase of the intermediates in the last half of the TCAC
      suggests the involvement of glutaminolysis, in which glutamine is converted to
      lactate via the last half of the TCAC. CONCLUSIONS: It is suggested that OSCC
      tissues show the Warburg effect, which stems from the combined enhancement of
      glucose consumption and glutaminolysis.

PMID- 24927639
TI  - Estimation of health-related utility (EQ-5D index) in subjects with seasonal
      allergic rhinoconjunctivitis to evaluate health gain associated with sublingual
      grass allergen immunotherapy.
AB  - BACKGROUND: Grass allergen immunotherapy (AIT) reduces symptom severity in
      seasonal allergic rhinoconjunctivitis (ARC) but its impact on general health
      related utility has not been characterised for the purposes of economic
      evaluation. The aim of this study was to model the preferred measure of utility,
      EQ-5D index, from symptom severity and estimate incremental quality adjusted life
      years (QALYs) associated with SQ-standardised grass immunotherapy tablet
      (GRAZAX(r), 75,000 SQ-T/2,800 BAU, ALK, Denmark). METHODS: Data were analysed
      from five consecutive pollen seasons in a randomised placebo controlled trial of
      GRAZAX(r). Binomial and Gaussian mixed effects modelling related weekly EQ-5D
      index score to daily symptom and medication scores (DSS & DMS respectively). In
      turn, daily EQ-5D index was estimated from ARC symptoms and medication use.
      RESULTS: DSS and DMS were the principal predictors of 'perfect' health (EQ-5D =
      1.000; binomial) and 'imperfect' health (EQ-5D < 1.000; Gaussian). Each unit
      increase in DSS and DMS reduced the odds of 'perfect' health (EQ-5D = 1.000) by
      27% and 16% respectively, and reduced 'imperfect' health by 0.17 and 0.13,
      respectively. Gender remained the only other significant main fixed effect (Male
      odds ratio [OR] = 1.82). Incremental estimated EQ-5D index utility for GRAZAX(r)
      was observed from day -30 to day +70 of the pooled pollen season; mean daily
      utility for GRAZAX(r) = 0.938 units (95%CI 0.932-0.943) vs. 0.914 (0.907-0.921)
      for placebo, an incremental difference of 0.0238 (p < 0.001). This translates
      into an incremental 0.0324 Quality Adjusted Life Years over the five year study
      period. CONCLUSIONS: ARC symptoms and medication use are the main predictors of
      EQ-5D index. The incremental QALYs observed for GRAZAX(r) may not fully describe
      the health benefits of this treatment, suggesting that economic modelling may be
      conservative.

PMID- 24927640
TI  - Validation of the Greek OSD-6 quality of life questionnaire in children
      undergoing polysomnography.
AB  - OBJECTIVE: OSD-6 is a disease specific questionnaire for pediatric obstructive
      sleep apnea (OSA). The aims of this study were to validate OSD-6 in Greek
      language and correlate OSD-6 with polysomnography results. STUDY DESIGN:
      Prospective study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: OSD-6
      questionnaire was translated to Greek and back to English. A prospective study
      was conducted on children undergoing overnight polysomnography due to snoring and
      disrupted sleep. Test-retest evaluation was carried out. Internal consistency and
      test-retest reliability were evaluated. Validity was assessed by exploring
      correlations between OSD-6 scores and apnea-hypopnea index (AHI), and by
      comparing total scores of OSA and non-OSA groups. Responsiveness was assessed by
      comparing preoperative to postoperative total scores in OSA children who
      underwent adenotonsillectomy. RESULTS: Test-retest evaluation of 91 subjects
      showed good internal consistency (Cronbach's alpha 0.860 for test and 0.873 for
      retest) and reliability (Pearson's correlation coefficients between test and
      retest scores: 0.751-0.546; p<0.01). Total and domains' OSD-6 scores and AHI were
      significantly correlated (Spearman's correlation coefficients: 0.277-0.630;
      p<0.01), while children with OSA had higher total OSD-6 score than those without
      OSA (median (interquartile range): 16 (11) vs. 10 (7), respectively; p<0.01),
      indicating good validity. Postoperative OSD-6 scores were significantly lower
      than preoperative (2.84 +/- 3.21 vs. 15.42 +/- 6.48, respectively; p<0.001),
      suggesting good responsiveness. CONCLUSION: The Greek version of the OSD-6
      questionnaire proved to be a valid instrument with satisfactory internal
      consistency, reliability, validity and responsiveness. Furthermore, in our study
      OSD-6 was significantly correlated to polysomnography results.

PMID- 24927641
TI  - Understanding drug resistance in malaria parasites: basic science for public
      health.
AB  - The worlds of basic scientists and those involved in treating patients and making
      public health decisions do not always intersect. Yet, assuring that when patients
      are treated, they are efficiently and completely cured, and that public health
      decisions are based on solid evidence requires a broad foundation of up to date
      basic research. Research on the malaria parasite, Plasmodium falciparum provides
      a useful illustration of the role that basic scientific studies have played in
      the very long relationship between humans and this deadly parasite. Drugs have
      always been a principal tool in malaria treatment. The ongoing struggle between
      evolution of resistance to antimalarials by the parasite and public health
      responses is used here as an illustration of the key contributions of basic
      scientists to this long history. 

PMID- 24927642
TI  - Self-processing of a barley subtilase expressed in E. coli.
AB  - The barley protease BAJ93208 belongs to the subtilase family of serine proteases.
      We have expressed BAJ93208 in the cytoplasm of the Escherichiacoli strain SHuffle
      C3030 using a rhamnose-inducible promoter. The expression construct included a
      (His)6-tag at the N-terminus and a strep-tag at the C-terminus. Western blot
      analysis revealed that the protein was processed at the N- and C-terminus. To
      exclude that this processing was due to contaminating E. coli proteases, a
      mutated BAJ93208 protease was constructed. This inactive mutant was not
      processed, demonstrating that the processing was an autocatalytic process. To
      define the exact cleavage sites mass spectrometry was used which detected four
      differently processed versions of the protease. At the N-terminus, the self
      processing removed the internal inhibitor and an additional 19 amino acids. At
      the C-terminus there was a cleavage site after Ala(765) which also removed the
      strep-tag. This explained the inability to detect the purified (His)6-BAJ93208
      strep protease with an anti-strep-tag antibody. Finally, an additional alanine
      was removed either at the N-terminus (Ala(119)) or at the C-terminus (Ala(764)). 

PMID- 24927643
TI  - Biophysical characterization of the outer membrane polysaccharide export protein
      and the polysaccharide co-polymerase protein from Xanthomonas campestris.
AB  - This study investigated the structural and biophysical characteristics of GumB
      and GumC, two Xanthomonas campestris membrane proteins that are involved in
      xanthan biosynthesis. Xanthan is an exopolysaccharide that is thought to be a
      virulence factor that contributes to bacterial in planta growth. It also is one
      of the most important industrial biopolymers. The first steps of xanthan
      biosynthesis are well understood, but the polymerization and export mechanisms
      remain unclear. For this reason, the key proteins must be characterized to better
      understand these processes. Here we characterized, by biochemical and biophysical
      techniques, GumB, the outer membrane polysaccharide export protein, and GumC, the
      polysaccharide co-polymerase protein of the xanthan biosynthesis system. Our
      results suggested that recombinant GumB is a tetrameric protein in solution. On
      the other hand, we observed that both native and recombinant GumC present
      oligomeric conformation consistent with dimers and higher-order oligomers. The
      transmembrane segments of GumC are required for GumC expression and/or stability.
      These initial results provide a starting point for additional studies that will
      clarify the roles of GumB and GumC in the xanthan polymerization and export
      processes and further elucidate their functions and mechanisms of action.

PMID- 24927644
TI  - Gross and microscopic pathology of hard and soft corals in New Caledonia.
AB  - We surveyed the reefs of Grande Terre, New Caledonia, for coral diseases in 2010
      and 2013. Lesions encountered in hard and soft corals were systematically
      described at the gross and microscopic level. We sampled paired and normal
      tissues from 101 and 65 colonies in 2010 and 2013, respectively, comprising 51
      species of corals from 27 genera. Tissue loss was the most common gross lesion
      sampled (40%) followed by discoloration (28%), growth anomalies (13%), bleaching
      (10%), and flatworm infestation (1%). When grouped by gross lesions, the
      diversity of microscopic lesions as measured by Shannon-Wiener index was highest
      for tissue loss, followed by discoloration, bleaching, and growth anomaly. Our
      findings document an extension of the range of certain diseases such as Porites
      trematodiasis and endolithic hypermycosis (dark spots) to the Western Pacific as
      well as the presence of a putative cnidarian endosymbiont. We also expand the
      range of species infected by cell-associated microbial aggregates, and confirm
      the trend that these aggregates predominate in dominant genera of corals in the
      Indo-Pacific. This study highlights the importance of including histopathology as
      an integral component of baseline coral disease surveys, because a given gross
      lesion might be associated with multiple potential causative agents. 

PMID- 24927645
TI  - High prevalence of toxin producing enteropathogenic Vibrios among estuarine crab
      in Ganges delta of West Bengal, India.

PMID- 24927646
TI  - Beneficial effects of phlorizin on diabetic nephropathy in diabetic db/db mice.
AB  - AIMS: This study observes the effects of phlorizin on diabetic nephrology in
      db/db diabetic mice and explores possible underlying mechanisms. METHODS: Sixteen
      diabetic db/db mice and eight age-matched db/m mice were divided into three
      groups: vehicle-treated diabetic group (DM group), diabetic group treated with
      phlorizin (DMT group) and normal control group (CC group). Phlorizin was given in
      normal saline solution by intragastric administration for 10 weeks.
      Differentially expressed proteins in three groups were identified using iTRAQ
      quantitative proteomics and the data were further analyzed with ingenuity pathway
      analysis. RESULTS: The body weight and serum concentrations of fasting blood
      glucose (FBG), advanced glycation end products (AGEs), total cholesterol,
      triglycerides, blood urea nitrogen, creatinine and 24-h urine albumin were
      increased in the DM group compared to those of the CC group (P<0.05), and they
      were decreased by treatment with phlorizin (P<0.05). Morphologic observations
      showed phlorizin markedly attenuated renal injury. Phlorizin prevented diabetic
      nephropathy by regulating the expression of a series of proteins involved in
      renal and urological disease, molecular transport, free radical scavenging, and
      lipid metabolism. CONCLUSIONS: Phlorizin protects mice from diabetic nephrology
      and thus may be a novel therapeutic approach for the treatment of diabetic
      nephrology.

PMID- 24927648
TI  - Establishment of hormone reference intervals for infants born < 30 weeks'
      gestation.
AB  - OBJECTIVE: Preterm infants, especially those born very preterm (<32 weeks'
      gestation), suffer a number of morbidities. Immaturity of the endocrine system
      and its potential impact on morbidity is the subject of numerous studies. Hormone
      concentrations are sometimes measured in very preterm infants, however there are
      little normative data available to be able to interpret the results. The aim of
      this study was to describe age appropriate hormone reference intervals for babies
      born less than 30 weeks' gestation. STUDY DESIGN: Samples were collected at 1, 4,
      7, 14, 21, 28 and 42 days after birth from babies born 23-29 weeks' gestation.
      The serum was analyzed for seven hormones by automated chemiluminescent
      immunoassay (Siemens Immulite 2000). Results from the 107 infants who survived
      beyond 40 weeks' corrected gestational age were included in the data analysis.
      RESULTS: Cortisol, dehydroepiandrosterone sulfate, growth hormone and
      progesterone levels were highest during the first seven days with levels up to
      10,801nmol/L; 26.6MUmol/L; 343mU/L; and >63.6nmol/L respectively. Free thyroxine
      levels were as low as <2.6pmol/L for the first 28 days with the nadir at 7days.
      Estradiol levels ranged from <73 to 1626pmol/L over the six weeks. Reference
      intervals for IGF-1 could not be established as the levels were below the
      analyzer's sensitivity. There were no differences in reference intervals between
      male and female infants. CONCLUSIONS: We describe gestation appropriate reference
      intervals for six hormones measured in babies born <30 weeks' gestation.
      Utilization of these reference intervals permits the correct and timely
      interpretation of results to the clinician.

PMID- 24927649
TI  - The use of biomechanics across sports science and sports medicine.

PMID- 24927647
TI  - Serum phospholipid omega-3 polyunsaturated fatty acids and insulin resistance in
      type 2 diabetes mellitus and non-alcoholic fatty liver disease.
AB  - AIMS: To investigate the relationship between serum phospholipid omega-3
      polyunsaturated fatty acids (omega-3 PUFAs) and insulin resistance (IR) in
      patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver
      disease (NAFLD). METHODS: 51 patients with T2DM and NAFLD (T2DM+NAFLD group), 50
      with T2DM alone (T2DM group), 45 with NAFLD alone (NAFLD group), and 42 healthy
      control subjects (NC group) were studied. Serum omega-3 PUFA profiles were
      analyzed by gas chromatography, and alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), gamma-glutamyltransferase (GGT), and serum lipid
      concentrations were measured. Insulin resistance was assessed by the homeostasis
      model assessment method (HOMA-IR). RESULTS: HOMA-IR levels were higher in the
      T2DM+NAFLD group than in the T2DM, NAFLD and NC groups (p<0.05), as were ALT,
      AST, GGT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C),
      and triglyceride (TG) concentrations (p<0.05). Conversely, serum omega-3 PUFA
      levels were significantly lower in the T2DM+NAFLD group than in the other groups
      (p<0.05). The omega-3 PUFA level was negatively correlated with HOMA-IR, TC, LDL
      C and TG. CONCLUSIONS: Serum phospholipid omega-3 PUFA levels were significantly
      decreased in patients with T2DM and NAFLD, and were negatively related with
      insulin resistance. Thus, reduced omega-3 PUFAs may play an important role in the
      development of T2DM and NAFLD.

PMID- 24927650
TI  - [Post-term pregnancy in the broad ligament].
AB  - Post-term pregnancy in the broad ligament is rarely described in the literature.
      A 33-year-old woman, grava 2 para 1, not followed-up during gestation was
      admitted at 44 weeks of gestation. The fetus was dead and in transversal
      position, as shown by ultrasound. A cesarean section was performed and the fetus
      was extracted from the right broad ligament. The placenta was inserted on the
      surface of the posterior wall of the uterus. Blood loss was estimated at 1200 mL
      and the patient received isogroup total blood. There was no major complication.

PMID- 24927651
TI  - [Diagnosis, treatment, and follow-up of cesarean scar pregnancy].
AB  - OBJECTIVES: Cesarean scar pregnancy is a rare entity. This situation may induce
      uterine rupture and/or a massive life-threatening hemorrhage. The standard
      treatment is laparotomy surgery, but in situ injections to replace invasive
      surgery. The objective of this study was to focus on the diagnosis, optimal
      management and long-term follow-up of the patients. PATIENTS AND METHODS: Data
      from 6 patients with diagnosis of cesarean scar pregnancy between 2007 and 2013
      at Lariboisiere hospital were retrospectively collected. RESULTS: Endovaginal
      ultrasound succeeded to diagnose all cases. Four patients were treated with in
      situ injection of methotrexate performing a vaginal way (n=2) or laparoscopy
      (n=2) and two others using systemic injection. One patient was complicated by
      hemorrhagic shock requiring iterative embolizations. Three patients achieved a
      new pregnancy, with one recurrent scar pregnancy complicated by massive
      hemorrhage. DISCUSSION AND CONCLUSION: Diagnosis and treatment of cesarean scar
      pregnancies must be done precociously because of high hemorrhage risks.
      Endovaginal ultrasound is the gold standard exam. Treatment is non-consensual,
      but methotrexate in situ injection is effective and safer. Monitoring the
      decrease of HCG levels and ultrasonography supervision of gestational sac size
      and its vascularization must be performed. Due to the risk of recurrence, any
      subsequent pregnancy shows a high risk of complications.

PMID- 24927652
TI  - Assessment and refinement of eukaryotic gene structure prediction with gene
      structure-aware multiple protein sequence alignment.
AB  - BACKGROUND: Accurate computational identification of eukaryotic gene organization
      is a long-standing problem. Despite the fundamental importance of precise
      annotation of genes encoded in newly sequenced genomes, the accuracy of predicted
      gene structures has not been critically evaluated, mostly due to the scarcity of
      proper assessment methods. RESULTS: We present a gene-structure-aware multiple
      sequence alignment method for gene prediction using amino acid sequences
      translated from homologous genes from many genomes. The approach provides rich
      information concerning the reliability of each predicted gene structure. We have
      also devised an iterative method that attempts to improve the structures of
      suspiciously predicted genes based on a spliced alignment algorithm using
      consensus sequences or reliable homologs as templates. Application of our methods
      to cytochrome P450 and ribosomal proteins from 47 plant genomes indicated that 50
      ~ 60 % of the annotated gene structures are likely to contain some defects.
      Whereas more than half of the defect-containing genes may be intrinsically
      broken, i.e. they are pseudogenes or gene fragments, located in unfinished
      sequencing areas, or corresponding to non-productive isoforms, the defects found
      in a majority of the remaining gene candidates can be remedied by our iterative
      refinement method. CONCLUSIONS: Refinement of eukaryotic gene structures mediated
      by gene-structure-aware multiple protein sequence alignment is a useful strategy
      to dramatically improve the overall prediction quality of a set of homologous
      genes. Our method will be applicable to various families of protein-coding genes
      if their domain structures are evolutionarily stable. It is also feasible to
      apply our method to gene families from all kingdoms of life, not just plants.

PMID- 24927654
TI  - An evaluation of the Head and Neck Cancer Patient Concerns Inventory across the
      Merseyside and Cheshire Network.
AB  - The Patient Concerns Inventory (PCI-H&N) is a carefully designed 57-item
      checklist specifically for use in routine follow-up clinics for patients with
      head and neck cancer. Although developmental work at one hospital has been very
      positive, its use had not been evaluated across a wider network. The aim of this
      project was to evaluate use of the inventory across the Merseyside and Cheshire
      cancer network. Patients from 5 hospitals were included and 66 patients, 8
      doctors, and 6 nurse specialists took part. Almost all patients found the
      inventory easy or very easy to complete and it caused no notable problems with
      the running of appointments. Two-thirds felt that all or most of the items
      mentioned were talked about in the consultations and no patient felt that the
      consultation had been made worse. Two-thirds felt that it had helped them
      communicate with the doctor, while some felt that communication was already
      excellent and beyond improvement. Only a small minority (12%) thought that it
      could or definitely would lead to disappointment because needs might not be met.
      Most patients definitely wanted to continue using the inventory and only 5%
      definitely did not. Most of the doctors and specialist nurses saw its potential
      benefit in clinical practice. However, some practical, administrative, and
      educational aspects need to be addressed before it can be used more widely. It is
      likely that the inventory will be incorporated into practice at each clinic and
      locality in different ways.

PMID- 24927653
TI  - The American cranberry: first insights into the whole genome of a species adapted
      to bog habitat.
AB  - BACKGROUND: The American cranberry (Vaccinium macrocarpon Ait.) is one of only
      three widely-cultivated fruit crops native to North America- the other two are
      blueberry (Vaccinium spp.) and native grape (Vitis spp.). In terms of taxonomy,
      cranberries are in the core Ericales, an order for which genome sequence data are
      currently lacking. In addition, cranberries produce a host of important
      polyphenolic secondary compounds, some of which are beneficial to human health.
      Whereas next-generation sequencing technology is allowing the advancement of
      whole-genome sequencing, one major obstacle to the successful assembly from short
      read sequence data of complex diploid (and higher ploidy) organisms is
      heterozygosity. Cranberry has the advantage of being diploid (2n = 2x = 24) and
      self-fertile. To minimize the issue of heterozygosity, we sequenced the genome of
      a fifth-generation inbred genotype (F >= 0.97) derived from five generations of
      selfing originating from the cultivar Ben Lear. RESULTS: The genome size of V.
      macrocarpon has been estimated to be about 470 Mb. Genomic sequences were
      assembled into 229,745 scaffolds representing 420 Mbp (N50 = 4,237 bp) with 20X
      average coverage. The number of predicted genes was 36,364 and represents 17.7%
      of the assembled genome. Of the predicted genes, 30,090 were assigned to
      candidate genes based on homology. Genes supported by transcriptome data totaled
      13,170 (36%). CONCLUSIONS: Shotgun sequencing of the cranberry genome, with an
      average sequencing coverage of 20X, allowed efficient assembly and gene calling.
      The candidate genes identified represent a useful collection to further study
      important biochemical pathways and cellular processes and to use for marker
      development for breeding and the study of horticultural characteristics, such as
      disease resistance.

PMID- 24927655
TI  - See-and-treat surgery for facial skin cancer.
AB  - See-and-treat surgery has been described as an efficient means of streamlining
      specialist diagnosis and treatment, and is commonly employed in gynaecology to
      reduce the delay between cytological screening and definitive treatment of
      cervical neoplasia. Relatively young patients with predominantly benign skin
      lesions have been treated in see-and-treat clinics but only in the context of
      referrals from primary care. The author describes the treatment of tertiary
      referrals for facial skin malignancies under local anaesthesia at these clinics,
      and analyses their acceptability to patients. A total of 100 consecutive patients
      were included. Data on age, coexisting conditions, diagnosis, site and size of
      lesion, operation, and outcomes including complications and completeness of
      excision, were collected. A questionnaire seeking patients' opinions was also
      used. Ninety patients were treated and 98 lesions were removed, 94% of which were
      malignant. The complete excision rate was 95%. There were no complications, and
      98% of patients were satisfied with the service. See-and-treat surgery is an
      effective, safe, and acceptable means of providing surgical management of facial
      skin malignancies.

PMID- 24927656
TI  - Cardiac dysrhythmias in pediatric patients during general anesthesia.

PMID- 24927657
TI  - [Multiple myeloma].

PMID- 24927658
TI  - [Radiological diagnostics of multiple myeloma].
AB  - CLINICAL/METHODICAL ISSUE: Robust and reliable imaging methods are required to
      estimate the skeletal tumor load in multiple myeloma, as well as for the
      diagnosis of extraskeletal manifestations. Imaging also plays an essential role
      in the assessment of fracture risk and of vertebral fractures. STANDARD
      RADIOLOGICAL METHODS: The conventional skeletal survey has been the gold standard
      in the imaging of multiple myeloma for many years. METHODICAL INNOVATIONS: Other
      modalities which have been investigated and are in use are whole-body computed
      tomography (WBCT), 18F-fluorodeoxyglucose positron emission tomography computed
      tomography (FDG PET-CT) and whole-body magnetic resonance imaging (WBMRI). These
      techniques are able to depict both mineralized bone and the bone marrow with a
      high sensitivity for myeloma lesions. PERFORMANCE: Several studies have shown
      that cross-sectional imaging is superior to the skeletal survey in the detection
      of myeloma lesions and WBMRI has been shown to be significantly more sensitive
      than WBCT for the detection of focal myeloma lesions as well as for diffuse
      infiltration. The FDG PET-CT technique has a sensitivity comparable to WBMRI.
      ACHIEVEMENTS: Due to the higher sensitivity in the detection of myeloma lesions
      WBCT and WBMRI should replace the skeletal survey. PRACTICAL RECOMMENDATIONS: A
      WBCT should be performed if there is suspicion of multiple myeloma. If no focal
      lesions are found WBMRI or at least MRI of the spine and pelvis should be
      additionally performed if available. If WBMRI has been initially performed and
      focal lesions are present, an additional WBCT may be performed to assess the
      extent of bone destruction and fracture risk. In cases of monoclonal gammopathy
      of undetermined significance (MGUS), solitary and smoldering myeloma, a WBMRI, if
      available, should be performed in addition to WBCT.

PMID- 24927659
TI  - [Imaging in smoldering (asymptomatic) multiple myeloma. Past, present and
      future].
AB  - CLINICAL ISSUE: Emerging clinical trial data support treatment of high-risk
      smoldering multiple myeloma (SMM) upon diagnosis, and not only at the time of
      progression to symptomatic complications (multiple myeloma). Early detection of
      bone and/or bone marrow involvement by sensitive imaging modalities may help
      define SMM patients at a high risk of progression. STANDARD RADIOLOGICAL METHODS:
      Current (2011) consensus guidelines recognize skeletal survey as a cornerstone
      modality for assessment of bone involvement at initial diagnosis and during
      follow-up of SMM. Skeletal survey has severe limitations related to
      underdetection of bone lesions and also provides no information on bone marrow
      abnormalities. METHODICAL INNOVATIONS: Modern imaging strategies such as
      fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT) and MRI, in
      conjunction with functional innovations, provide improved estimates of global
      abnormalities in the bone marrow and bone compartments. These methods have the
      potential to objectively quantify early transformation from SMM to multiple
      myeloma. PERFORMANCE: Although frequently used for staging and risk
      prognostication in multiple myeloma, modern imaging techniques have only been
      evaluated to a limited extent in SMM. Scant data in SMM indicate the prognostic
      value of two or more MRI-detected focal bone marrow abnormalities, which, if
      present, predict rapid progression to multiple myeloma. Data evaluating the role
      of FDG PET/CT in detecting early bone marrow abnormalities as an aid to
      predicting risk or directing treatment in SMM is currently lacking. ACHIEVEMENTS:
      The superior specificity and sensitivity of modern imaging techniques compared to
      skeletal survey suggest that these should have a place in standard practice
      management of patients at a high risk of SMM progression. The model imaging of
      the future should be an all-in-one strategy offering high diagnostic performance
      for bone marrow abnormalities and low-volume bone lesions, as well as allowing
      monitoring by minimizing radiation exposure and the need for contrast agents.
      PRACTICAL RECOMMENDATIONS: Newer imaging techniques need to be validated in
      prospective clinical trials assessing the SMM to multiple myeloma transition,
      with the aim of enabling appropriate management decisions. Efforts are also
      needed to improve the costs and availability of whole-body MRI and/or FDG PET/CT,
      in order to facilitate their widespread adoption as first-line detection
      modalities. Future clinical trials of therapeutic agents using earlier detection
      strategies will have to be carefully designed and take into consideration the
      risk of lead-time and length-time biases, which might falsely demonstrate longer
      overall survival. The English full text version of this article is available at
      SpringerLink (under "Supplemental").

PMID- 24927660
TI  - [Morphological and functional cartilage imaging].
AB  - Excellent morphological imaging of cartilage is now possible and allows the
      detection of subtle cartilage pathologies. Besides the standard 2D sequences, a
      multitude of 3D sequences are available for high-resolution cartilage imaging.
      The first part therefore deals with modern possibilities of morphological
      imaging. The second part deals with functional cartilage imaging with which it is
      possible to detect changes in cartilage composition and thus early osteoarthritis
      as well as to monitor biochemical changes after therapeutic interventions.
      Validated techniques such as delayed gadolinium-enhanced magnetic resonance
      imaging of cartilage (dGEMRIC) and T2 mapping as well the latest techniques, such
      as the glycosaminoglycan chemical exchange-dependent saturation transfer
      (gagCEST) technique will be discussed. 

PMID- 24927661
TI  - Permanent central diabetes insipidus as a complication of sphenoid sinus
      mucocele.
AB  - Although mucocele is a benign lesion, its unavoidable expansions may result in
      irreversible damages in adjacent organs. In spheno-ethmoid mucoceles which are
      extremely rare, this condition may cause more severe problems. Central diabetes
      insipidus, developed secondary to sphenoid sinus mucocele, was detected in a 54
      year-old male patient, who underwent endoscopic sinus surgery 2 times due to
      nasal polyposis. Endoscopic sphenoid mucocele marsupialization was performed to
      the patient, but despite partial regression in the 1-year follow up, complete
      recovery was not observed. 

PMID- 24927662
TI  - Multiple relapses of visceral leishmaniasis in a patient with HIV in India: a
      treatment challenge.
AB  - Visceral Leishmaniasis (VL) is an opportunistic infection amongst HIV-infected
      people in several endemic countries, and the clinical management of this co
      infection poses several challenges. Here we describe a co-infected patient in
      India who failed to respond to miltefosine monotherapy and subsequently relapsed
      following two further (different) regimens of liposomal amphotericin B. He was
      then successfully treated with a combination of 30 mg/kg liposomal amphotericin B
      and 14 days of 100mg/day oral miltefosine.

PMID- 24927663
TI  - Epidemiology characteristics of respiratory viruses found in children and adults
      with respiratory tract infections in southern China.
AB  - BACKGROUND: The World Health Organization (WHO) ranks respiratory tract infection
      (RTI) as the second leading cause of death worldwide for children under 5 years
      of age. The aim of this work was to evaluate the epidemiology characteristics of
      respiratory viruses found in children and adults with RTI from July 2009 to June
      2012 in southern China. METHODS: In this work, a total of 14 237 nasopharyngeal
      swabs (14 237 patients from 25 hospitals) were analyzed, and seven respiratory
      viruses (influenza virus, respiratory syncytial virus, parainfluenza virus,
      adenovirus, human metapneumovirus, human coronavirus, human bocavirus) were
      detected using PCR/RT-PCR from nasopharyngeal swabs. RESULTS: The demographic
      characteristics, viral prevalence, age distribution, seasonal distribution, and
      pathogen spectrum of the patients with RTIs were analyzed. Co-infection was
      observed in 483 specimens, but it was more common in male patients, inpatients,
      children, and young adults. It varied by season, being more prevalent in the
      spring and summer and less so in the winter. Human coronavirus and human
      bocavirus were the most common pathogens, tending to occur in co-infection with
      other respiratory viruses. CONCLUSIONS: This work adds to our knowledge of the
      epidemiology characteristics of these seven common respiratory viruses among
      patients with RTI in southern China. The detection of the specific viral causes
      of infection provides a useful starting point for an understanding of illness
      attributable to respiratory infection, and might also provide data relevant to
      the development of prevention strategies.

PMID- 24927664
TI  - Usefulness of broad-range PCR plus sequencing for the diagnosis of bacteremia due
      to a lung abscess.
AB  - The early detection and treatment of sepsis in patients is essential for a
      positive outcome. Microbiological analysis of blood cultures, as the gold
      standard for diagnosis, is rather slow. However, more rapid methods like PCR have
      become available recently and are being evaluated clinically. We present data
      from the monitoring of a patient with sepsis who was on anti-infective treatment.
      The patient was positive for Streptococcus pneumoniae by broad-range PCR and
      sequence analysis in a blood sample and resected lung tissue specimen, the latter
      embedded in paraffin, while blood culture diagnostics remained negative. 

PMID- 24927665
TI  - Mini review: current molecular methods for the detection and quantification of
      hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1.
AB  - The detection of acute human immunodeficiency virus (HIV), hepatitis B virus
      (HBV), and hepatitis C virus (HCV) infection is vital for controlling the spread
      of HIV, HBV, and HCV to uninfected individuals. Considering that these viruses
      have high replication rates and are undetectable by serological markers, early
      detection upon transmission is crucial. Various nucleic acid assays have been
      developed for diagnostics and therapeutic monitoring of infections. In the past
      decade, rapid and sensitive molecular techniques such as PCR have revolutionized
      the detection of a variety of infectious viruses, including HIV, HCV, and HBV.
      Here, we describe two of the most commonly used licensed methods for the
      detection and quantification of HIV, HCV, and HBV: the cobas TaqScreen MPX (PCR)
      test and the Tigris System. We used transcription-mediated amplification to
      review and compare the development and efficiency of these technologies. 

PMID- 24927666
TI  - Comparative expression profiles of genes related to oocyte development in goats
      after long-term feeding with biodiesel castor industry residues.
AB  - The aim of this study was to determine whether the consumption of detoxified
      castor meal (DCM) by goats over a long period of time affects mRNA levels in
      oocytes, and in mural granulosa and cumulus cells. A total of 41 adult does were
      supplemented (DCM group, n=21) or not (control group, n=20) with detoxified
      castor meal (DCM) for a period of 500 days. Then, 13 and 12 does were randomly
      selected for slaughter from the DCM and control treatments groups, respectively,
      for the determination of the number of visible ovarian follicles, retrieved
      cumulus-oocyte complexes (COCs), and viable and non-viable oocytes. The relative
      expression levels for distinct genes were determined by quantitative PCR in
      viable immature oocytes prior to in vitro maturation (IVM), in oocytes attaining
      or not the metaphase stage after IVM, as well as in granulosa cells obtained upon
      oocyte collection, and in cumulus cells obtained after IVM. The number of
      follicles >=4 mm did not differ between treatments (overall mean 23.3 +/- 2.0)
      and no significant differences were observed in the recovery of viable, non
      viable, or total mean numbers of oocytes (control group: 44.7 +/- 4.6, DCM group:
      54.9 +/- 5.9, respectively) between control and DCM fed goats. The maturation
      rate was significantly higher for control than DCM oocytes (58.0% vs. 45.3%;
      P<0.05). The mRNA levels in immature COC for controls were significantly higher
      for GLUT1 and lower for HSP70 (P<0.05) than for DCM. Following maturation, MII
      oocytes from both treatments had mRNA levels that were significantly higher for
      GDF9 and lower for BMP15 than for NC oocytes (P<0.05). In cumulus cells, the mRNA
      levels were significantly higher for LHR, FSHR, LeptinR, and IGF1, and lower for
      MnSOD in the control group compared with the DCM group (P<0.05). In conclusion,
      the inclusion of DCM in goat feed for long periods of time changed gene
      expression in immature oocytes and in cumulus cells. This was reflected by a
      decrease in the in vitro oocyte maturation rate.

PMID- 24927667
TI  - Regulation of gene expression by tobacco product preparations in cultured human
      dermal fibroblasts.
AB  - Skin fibroblasts comprise the first barrier of defense against wounds, and
      tobacco products directly contact the oral cavity. Cultured human dermal
      fibroblasts were exposed to smokeless tobacco extract (STE), total particulate
      matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to
      those found in these extracts for 1h or 5h. Differences were identified in
      pathway-specific genes between treatments and vehicle using qRT-PCR. At 1h,
      IL1alpha was suppressed significantly by TPM and less significantly by STE.
      Neither FOS nor JUN was suppressed at 1h by tobacco products. IL8, TNFalpha,
      VCAM1, and NFkappaB1 were suppressed after 5h with STE, whereas only TNFalpha and
      NFkappaB1 were suppressed by TPM. At 1h with TPM, secreted levels of IL10 and
      TNFalpha were increased. Potentially confounding effects of nicotine were
      exemplified by genes such as ATF3 (5h), which was increased by nicotine but
      suppressed by other components of STE. Within 2h, TPM stimulated nitric oxide
      production, and both STE and TPM increased reactive oxygen species. The
      biological significance of these findings and utilization of the gene expression
      changes reported herein regarding effects of the tobacco product preparations on
      dermal fibroblasts will require additional research. 

PMID- 24927669
TI  - Impact of anti-tacking agents on properties of gas-entrapped membrane and
      effervescent floating tablets.
AB  - Tackiness caused by the gas-entrapped membrane (Eudragit((r))RL 30D) was usually
      observed during storage of the effervescent floating tablets, leading to failure
      in floatation and sustained release. In this work, common anti-tacking agents
      (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem.
      The impact of anti-tacking agent on the properties of free films and
      corresponding floating tablets was investigated. GMS was more effective than talc
      in reducing tackiness of the film. Addition and increasing amount of anti-tacking
      agents lowered the film mechanical strength, but the coating films were still
      strong and flexible enough to resist the generated gas pressure inside the
      floating tablet. Wettability and water vapor permeability of the film decreased
      with increasing level of anti-tacking agents as a result of their hydrophobicity.
      No interaction between anti-tacking agents and polymer was observed as confirmed
      by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and
      differential scanning calorimetry studies. Increasing amount of anti-tacking
      agents decreased time to float and tended to retard drug release of the floating
      tablets. Floating properties and drug release were also influenced by type of
      anti-tacking agents. The obtained floating tablets still possessed good floating
      properties and controlled drug release even though anti-tacking agent had some
      effects. The results demonstrated that the tackiness problem of the floating
      tablets could be solved by incorporating anti-tacking agent into the gas
      entrapped membrane.

PMID- 24927668
TI  - Nanoparticle ligand presentation for targeting solid tumors.
AB  - Among the many scientific advances to come from the study of nanoscience, the
      development of ligand-targeted nanoparticles to eliminate solid tumors is
      predicted to have a major impact on human health. There are many reports
      describing novel designs and testing of targeted nanoparticles to treat cancer.
      While the principles of the technology are well demonstrated in controlled lab
      experiments, there are still many hurdles to overcome for the science to mature
      into truly efficacious targeted nanoparticles that join the arsenal of agents
      currently used to treat cancer in humans. One of these hurdles is overcoming
      unwanted biodistribution to the liver while maximizing delivery to the tumor.
      This almost certainly requires advances in both nanoparticle stealth technology
      and targeting. Currently, it continues to be a challenge to control the loading
      of ligands onto polyethylene glycol (PEG) to achieve maximal targeting.
      Nanoparticle cellular uptake and subcellular targeting of genes and siRNA also
      remain a challenge. This review examines the types of ligands that have been most
      often used to target nanoparticles to solid tumors. As the science matures over
      the coming decade, careful control over ligand presentation on nanoparticles of
      precise size, shape, and charge will likely play a major role in achieving
      success. 

PMID- 24927671
TI  - An increased risk of ovarian cancer associated with polymorphism in BRCC5 gene in
      Caucasian populations.
AB  - Several reports on the association between the BRCC5 gene polymorphism and
      ovarian cancer risk have been published recently, but the estimates of the risk
      vary widely. We thus performed a meta-analysis in an effort to determine the
      association. To identify the eligible studies, we searched the PubMed, Embase,
      and CNKI databases, and reviewed all original studies retrieved as well as their
      citations. The risk of ovarian cancer was estimated using odds ratio (OR) and its
      95 % confidence interval (CI). Meta-analysis of seven comparisons revealed an
      obvious rise in the risk of ovarian cancer under the CC vs. GG contrast model (OR
      = 1.52, 95 % CI = 1.07-2.16, P OR = 0.020). A similar increase was also indicated
      in the CC vs. GC + GG model (OR = 2.10, 95 % CI = 1.51-2.93, P OR < 0.001). Our
      meta-analysis indicates that the BRCC5 polymorphism may be a candidate modifier
      of ovarian cancer risk in Caucasians.

PMID- 24927670
TI  - Exercise intervention studies in patients with peripheral neuropathy: a
      systematic review.
AB  - INTRODUCTION: Peripheral neuropathies (PNPs) encompass a large group of disorders
      of heterogeneous origin which can manifest themselves with sensory and/or motor
      deficits depending on the predominantly affected nerve fiber modality. It
      represents a highly prevalent disease group which can be associated with
      significant disability and poor recovery. Exercise has the potential to improve
      side effects of PNP. OBJECTIVE: Our objective in this systematic review was to
      analyze exercise interventions for neuropathic patients in order to evaluate the
      possible benefits of exercise. METHODS: Three independent reviewers used PubMed,
      MEDPILOT (MEDLINE), Cochrane, and relevant reference lists to obtain the data.
      Relevant studies were graded according to the Oxford Levels of Evidence. RESULTS:
      Eighteen studies (ten randomized controlled trials and eight controlled clinical
      trials) met all inclusion criteria. Three (diabetic) studies were ranked very
      high quality [1b (A)], nine high quality (four diabetes, one cancer, four others)
      [2b (B)], while six (four diabetes, two others) showed low quality (4/C). Current
      data suggests that exercise is a feasible, safe, and promising supportive measure
      for neuropathic patients. This is best documented for patients with diabetic
      peripheral neuropathy (DPN), suggesting that endurance training has the potential
      to prevent the onset of and reduce the progression of DPN. In general, balance
      exercises showed the highest effect on the motor as well as sensory symptoms in
      all types of PNP. CONCLUSION: Overall, balance training appears to be the most
      effective exercise intervention. Studies focusing exclusively on strength, or a
      combination of endurance and strength, appear to have a lower impact. For
      metabolically-induced neuropathies, endurance training also plays an important
      role. Further research with high methodological quality needs to be conducted in
      order to establish evidence-based clinical recommendations for neuropathic
      patients.

PMID- 24927672
TI  - High expression of CASK correlates with progression and poor prognosis of
      colorectal cancer.
AB  - Calcium/calmodulin-dependent serine protein kinase (CASK), which localizes at
      cell-cell adhesion sites and binds to the heparan sulfate proteoglycan syndecan
      2, is involved in cell proliferation, cytoskeletal remodeling, and cell
      migration. To demonstrate the role of CASK in colorectal cancer (CRC)
      carcinogenesis, we examined the expression of CASK and its binding protein
      syndecan-2 in human CRC tissues. The expression of CASK was measured in CRC
      specimens and the controls from adenomas and normal mucosae by
      immunohistochemical staining and Western blot analysis. Syndecan-2 protein level
      was tested in CRC samples and the controls by Western blot analysis. The
      correlations between CASK expression and clinicopathological variables, including
      disease-free survival (DFS) and overall survival (OS), were analyzed. Compared to
      the controls, both CASK and syndecan-2 expression were enhanced in CRC tissues.
      Furthermore, high expression of CASK and syndecan-2 was significantly correlated
      with advanced tumor stage, lymphatic invasion, lymph node metastasis, vascular
      invasion, liver metastasis, and unresectable metastatic CRC. Survival analysis
      showed that patients with low CASK staining had a significantly better survival
      compared to patients with high CASK staining. In multivariate analysis, CASK
      overexpression, advanced tumor stage, lymph node metastasis, vasvular invasion,
      and liver metastasis were independent prognostic factors of poor DFS and OS. Our
      present study indicates that CASK overexpression is associated with an
      unfavorable prognosis. CASK is an independent prognostic factor for CRC, which
      suggests that it is a novel and crucial predictor for CRC metastasis.

PMID- 24927673
TI  - Quantitative assessment of the associations between CD28 T > C polymorphism
      (rs3116496) and cancer risk.
AB  - Many studies have examined the association between CD28 T > C polymorphism
      (rs3116496) and cancer risk in various populations. However, results remained
      controversial. To assess this relationship more precisely, a meta-analysis was
      performed. A comprehensive literature search was performed using the PubMed
      database for relevant articles published (updated to January 1, 2014). Odds
      ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength
      of the association. A total of nine studies were selected for this meta-analysis,
      including 3,878 cases and 4,424 controls. The results indicated that CD28 T > C
      polymorphism (rs3116496) was not associated with the risk of cancer in overall
      population (CC + CT vs. TT, OR = 1.17, 95 %CI = 0.94-1.47, P H = 0.00; CC vs. CT
      + TT, OR = 1.26, 95 %CI = 0.92-1.73, P H = 0.86; CC vs. TT, OR = 1.27, 95 %CI =
      0.92-1.74, P H = 0.85; CT vs. TT, OR = 1.15, 95 %CI = 0.91-1.46, P H = 0.00; and
      C vs. T, OR = 1.17, 95 %CI = 0.97-1.41, P H = 0.00). In subgroup analysis
      according to cancer type, no significant association was found in cervical cancer
      or other cancer. However, in the subgroup analysis by ethnicity, the significant
      risk was found among Asians (CC + CT vs. TT, OR = 1.51, 95 %CI = 1.24-1.83, P H =
      0.05; C vs. T, OR = 1.46, 95 %CI = 1.22-1.74, P H = 0.11), but not among
      Caucasians. The result of this meta-analysis suggested that CD28 T > C
      polymorphism (rs3116496) may have an increased risk of cancer in Asians.

PMID- 24927674
TI  - Arthroscopic assessment of medial malleolar reduction.
AB  - INTRODUCTION: Ankle fractures treated with open reduction internal fixation are
      fixed in an effort to reestablish anatomic bony alignment and avoid a malunion,
      thereby diminishing the risk of post-traumatic arthritis. For a medial malleolar
      fracture, an articular step-off is likely more related to the risk of post
      traumatic arthritis than is a cortical step-off. However, the external cortical
      alignment is often used to judge the adequacy of reduction, as the articular
      component of the fracture is not as readily visualized. Arthroscopy has been used
      in various articular fractures as an aid to diagnosis and treatment. The current
      study prospectively assessed both the quality of medial malleolar reduction on
      the articular side using arthroscopy and the adequacy of using cortical cues to
      guide the articular reduction. METHODS: Twelve consecutive patients were enrolled
      in this prospective diagnostic study. All patients had medial malleolar fractures
      that required fixation. The outcome variables of interest were extra-articular
      fracture displacement and articular surface displacement. RESULTS: After
      reduction and provisional fixation, 10 of the 12 patients had an anatomic
      reduction based on cortical cues. On arthroscopy 7 of the 12 patients had an
      anatomic reduction. Four of the patients had a slight gap (<1 mm) at the anterior
      edge of the fracture. The last patient had an anterior gap just under 2 mm. Two
      patients had impaction of the medial malleolus that made reduction difficult and
      was recognized during arthroscopy after obtaining a reduction based on cortical
      cues. CONCLUSION: The cortical reduction of the medial malleolus often matched up
      with the articular reduction. However, in some patients, impaction of the medial
      malleolus made it so that the two did not match up. There are some cases in which
      extra-articular cues are insufficient to evaluate for intra-articular reduction.

PMID- 24927676
TI  - [Not Available].

PMID- 24927677
TI  - [Not Available].

PMID- 24927675
TI  - MPFL reconstruction using a quadriceps tendon graft: part 2: operative technique
      and short term clinical results.
AB  - BACKGROUND: We describe the preliminary clinical results of a new operative
      technique for MPFL reconstruction using a strip of quadriceps tendon (QT).
      METHODS:  PATIENTS: 17 patients (7 male, 10 female; mean age 21.5 years +/- 3.9)
      have been operated on with this technique. All patients were evaluated
      clinically, radiologically and with subjective questionnaires (Tegner-, Lysholm-,
      Kujala Score) pre-operatively and post-operatively at 6 and 12 months (m).
      SURGICAL TECHNIQUE: A 10 to 12 mm wide, 3mm thick and 8 to 10 cm long strip from
      the central aspect of quadriceps tendon is harvested subcutaneously. The tendon
      strip is then dissected distally on the patella, left attached, diverged 90
      degrees  medially underneath the medial prepatellar tissue and fixed with 2
      sutures. The graft is fixed in 20 degrees  of knee flexion with a bioabsorbable
      interference screw. RESULTS: Lysholm score at 6m was 81.9 +/- 11.7 and at 12 m
      88.1 +/- 10.9, Kujala score at 12 m was 89.2 +/- 7.1 and Tegner Score was 4.9 +/-
      2.0 (6m) and 5.0 +/- 1.9 (12 m). Two patients had a positive apprehension test at
      12 months. There was no re-dislocation during the follow-up period. CONCLUSION:
      MPFL reconstruction with a strip of QT harvested in a minimal invasive technique
      was found to be associated with good short term clinical results. We think that
      this technique presents a valuable alternative to common hamstring techniques for
      primary MPFL reconstruction in children and adults, as well as for MPFL revision
      surgery. LEVEL OF EVIDENCE: IV, prospective case series.

PMID- 24927678
TI  - [Not Available].

PMID- 24927679
TI  - Tough and flexible CNT-polymeric hybrid scaffolds for engineering cardiac
      constructs.
AB  - In the past few years, a considerable amount of effort has been devoted toward
      the development of biomimetic scaffolds for cardiac tissue engineering. However,
      most of the previous scaffolds have been electrically insulating or lacked the
      structural and mechanical robustness to engineer cardiac tissue constructs with
      suitable electrophysiological functions. Here, we developed tough and flexible
      hybrid scaffolds with enhanced electrical properties composed of carbon nanotubes
      (CNTs) embedded aligned poly(glycerol sebacate):gelatin (PG) electrospun
      nanofibers. Incorporation of varying concentrations of CNTs from 0 to 1.5% within
      the PG nanofibrous scaffolds (CNT-PG scaffolds) notably enhanced fiber alignment
      and improved the electrical conductivity and toughness of the scaffolds while
      maintaining the viability, retention, alignment, and contractile activities of
      cardiomyocytes (CMs) seeded on the scaffolds. The resulting CNT-PG scaffolds
      resulted in stronger spontaneous and synchronous beating behavior (3.5-fold lower
      excitation threshold and 2.8-fold higher maximum capture rate) compared to those
      cultured on PG scaffold. Overall, our findings demonstrated that aligned CNT-PG
      scaffold exhibited superior mechanical properties with enhanced CM beating
      properties. It is envisioned that the proposed hybrid scaffolds can be useful for
      generating cardiac tissue constructs with improved organization and maturation. 

PMID- 24927680
TI  - The effect of a polyurethane coating incorporating both a thrombin inhibitor and
      nitric oxide on hemocompatibility in extracorporeal circulation.
AB  - Nitric oxide (NO) releasing (NORel) materials have been extensively investigated
      to create localized increases in NO concentration by the proton driven
      diazeniumdiolate-containing polymer coatings and demonstrated to improve
      extracorporeal circulation (ECC) hemocompatibility. In this work, the NORel
      polymeric coating composed of a diazeniumdiolated dibutylhexanediamine (DBHD
      N2O2)-containing hydrophobic Elast-eonTM (E2As) polyurethane was combined with a
      direct thrombin inhibitor, argatroban (AG), and evaluated in a 4 h rabbit
      thrombogenicity model without systemic anticoagulation. In addition, the
      immobilizing of argatroban to E2As polymer was achieved by either a polyethylene
      glycol-containing (PEGDI) or hexane methylene (HMDI) diisocyanate linker. The
      combined polymer film was coated on the inner walls of ECC circuits to yield
      significantly reduced ECC thrombus formation compared to argatroban alone ECC
      control after 4 h blood exposure (0.6 +/- 0.1 AG/HMDI/NORel vs 1.7 +/- 0.2 cm(2)
      AG/HMDI control). Platelet count (2.8 +/- 0.3 AG/HMDI/NORel vs 1.9 +/- 0.1 *
      10(8)/ml AG/HMDI control) and plasma fibrinogen levels were preserved after 4 h
      blood exposure with both the NORel/argatroban combination and the AG/HMDI control
      group compared to baseline. Platelet function as measured by aggregometry
      remained near normal in both the AG/HMDI/NORel (63 +/- 5%) and AG/HMDI control
      (58 +/- 7%) groups after 3 h compared to baseline (77 +/- 1%). Platelet P
      selectin mean fluorescence intensity (MFI) as measured by flow cytometry also
      remained near baseline levels after 4 h on ECC to ex vivo collagen stimulation
      (16 +/- 3 AG/HMDI/NORel vs 11 +/- 2 MFI baseline). These results suggest that the
      combined AG/HMDI/NORel polymer coating preserves platelets in blood exposure to
      ECCs to a better degree than AG/PEGDI/NORel, NORel alone or AG alone. These
      combined antithrombin, NO-mediated antiplatelet effects were shown to improve
      thromboresistance of the AG/HMDI/NORel polymer-coated ECCs and move potential
      nonthrombogenic polymers closer to mimicking vascular endothelium. 

PMID- 24927681
TI  - Osteoclast resorption of beta-tricalcium phosphate controlled by surface
      architecture.
AB  - A resorbable bone graft substitute should mimic native bone in its capacity to
      support bone formation and be remodeled by osteoclasts (OCl) or other
      multinucleated cells such as foreign body giant cells (FBGC). We hypothesize that
      by changing the scale of surface architecture of beta-tricalcium phosphate (TCP),
      cellular resorption can be influenced. CD14(+) monocyte precursors were isolated
      from human peripheral blood (n = 4 independent donors) and differentiated into
      OCl or FBGC on the surface of TCP discs comprising either submicron- or micron
      scale surface topographical features (TCPs and TCPb, respectively). On
      submicrostructured TCPs, OCl survived, fused, differentiated, and extensively
      resorbed the substrate; however, on microstructured TCPb, OCl survival, TRAP
      activation, and fusion were attenuated. Importantly, no resorption was observed
      on microstructured TCPb. By confocal microscopy, OCl formed on TCPs contained
      numerous actin rings allowing for resorption, but not on TCPb. In comparison,
      FBGC could not resorb either TCP material, suggesting that osteoclast-specific
      machinery is necessary to resorb TCP. By tuning surface architecture, it appears
      possible to control osteoclast resorption of calcium phosphate. This approach
      presents a useful strategy in the design of resorbable bone graft substitutes. 

PMID- 24927682
TI  - Articular chondrocytes and mesenchymal stem cells seeded on biodegradable
      scaffolds for the repair of cartilage in a rat osteochondral defect model.
AB  - This work investigated the ability of co-cultures of articular chondrocytes and
      mesenchymal stem cells (MSCs) to repair articular cartilage in osteochondral
      defects. Bovine articular chondrocytes and rat MSCs were seeded in isolation or
      in co-culture onto electrospun poly(E-caprolactone) (PCL) scaffolds and implanted
      into an osteochondral defect in the trochlear groove of 12-week old Lewis rats.
      Additionally, a blank PCL scaffold and untreated defect were investigated. After
      12 weeks, the extent of cartilage repair was analyzed through histological
      analysis, and the extent of bone healing was assessed by quantifying the total
      volume of mineralized bone in the defect through microcomputed tomography.
      Histological analysis revealed that the articular chondrocytes and co-cultures
      led to repair tissue that consisted of more hyaline-like cartilage tissue that
      was thicker and possessed more intense Safranin O staining. The MSC, blank PCL
      scaffold, and empty treatment groups generally led to the formation of
      fibrocartilage repair tissue. Microcomputed tomography revealed that while there
      was an equivalent amount of mineralized bone formation in the MSC, blank PCL, and
      empty treatment groups, the defects treated with chondrocytes or co-cultures had
      negligible mineralized bone formation. Overall, even with a reduced number of
      chondrocytes, co-cultures led to an equal level of cartilage repair compared to
      the chondrocyte samples, thus demonstrating the potential for the use of co
      cultures of articular chondrocytes and MSCs for the in vivo repair of cartilage
      defects. 

PMID- 24927683
TI  - Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated
      multifunctional dendrimer-entrapped gold nanoparticles.
AB  - Development of multifunctional theranostic nanoplatforms for targeted cancer
      imaging and therapy still remains a great challenge. Herein, we report the use of
      multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) covalently
      linked with alpha-tocopheryl succinate (alpha-TOS) as a platform for targeted
      cancer computed tomography (CT) imaging and therapy. In this study, amine
      terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) conjugated with
      fluorescein isothiocyanate (FI), polyethylene glycol (PEG)-modified alpha-TOS,
      and PEGylated folic acid (FA) were used as templates to synthesize Au DENPs,
      followed by acetylation of the remaining dendrimer terminal amines. The formed
      multifunctional Au DENPs were characterized via different techniques. We show
      that the Au DENPs conjugated with approximately 9.8 alpha-TOS molecules per
      dendrimer and with an Au core size of 3.3 nm are water-dispersible, and stable
      under different pH and temperature conditions and in different aqueous media. The
      FA modification onto the Au DENPs enables efficient targeting of the particles to
      cancer cells overexpressing FA receptors (FAR), and effective targeted CT imaging
      of the cancer cells in vitro and the xenografted tumor model in vivo. Likewise,
      the covalent conjugation of alpha-TOS does not compromise its therapeutic
      activity, instead significantly improves its water solubility. Importantly,
      thanks to the role of FA-directed targeting, the formed multifunctional Au DENPs
      are able to exert the specific therapeutic efficacy of alpha-TOS to the FAR
      overexpressing cancer cells in vitro and the xenografted tumor model in vivo. The
      developed multifunctional Au DENPs may hold a great promise to be used as a
      unique theranostic nanoplatform for targeted CT imaging and therapy of different
      types of cancer. 

PMID- 24927684
TI  - Amphiphilic carboxymethyl chitosan-quercetin conjugate with P-gp inhibitory
      properties for oral delivery of paclitaxel.
AB  - An amphiphilic carboxymethyl chitosan-quercetin (CQ) conjugate was designed and
      synthesized for oral delivery of paclitaxel (PTX) to improve its oral
      bioavailability by increasing its water solubility and bypassing the P-gp drug
      efflux pumps. CQ conjugate had low critical micelle concentration (55.14 MUg/mL),
      and could self assemble in aqueous condition to form polymeric micelles (PMs).
      PTX-loaded CQ PMs displayed a particle size of 185.8 +/- 4.6 nm and
      polydispersity index (PDI) of 0.134 +/- 0.056. The drug-loading content (DL) and
      entrapment efficiency (EE) were 33.62 +/- 1.34% and 85.63 +/- 1.26%,
      respectively. Moreover, PTX-loaded CQ PMs displayed similar sustained-release
      profile in simulated gastrointestinal fluids (pH 1.2/pH 6.8) and PBS (pH 7.4). In
      situ intestinal absorption experiment showed that PTX-loaded CQ PMs significantly
      improved the effective permeability of PTX as compared to verapamil (P < 0.01).
      Likewise, PTX-loaded CQ PMs significantly enhanced the oral bioavailability of
      PTX, resulting in strong antitumor efficacy against tumor xenograft models with
      better safety profile as compared to Taxol((r)) and Taxol((r)) with verapamil.
      Overall, the results implicate that CQ PMs are promising vehicles for the oral
      delivery of water-insoluble anticancer drugs. 

PMID- 24927685
TI  - Pattern of brain activation during social cognitive tasks is related to social
      competence in siblings discordant for schizophrenia.
AB  - Measures of social competence are closely related to actual community functioning
      in patients with schizophrenia. However, the neurobiological mechanisms
      underlying competence in schizophrenia are not fully understood. We hypothesized
      that social deficits in schizophrenia are explained, at least in part, by
      abnormally lateralized patterns of brain activation in response to tasks engaging
      social cognition, as compared to healthy individuals. We predicted such patterns
      would be partly heritable, and therefore affected in patients' nonpsychotic
      siblings as well. We used a functional magnetic resonance image paradigm to
      characterize brain activation induced by theory of mind tasks, and two tests of
      social competence, the Test of Adaptive Behavior in Schizophrenia (TABS), and the
      Social Skills Performance Assessment (SSPA) in siblings discordant for
      schizophrenia and comparable healthy controls (n = 14 per group). Healthy
      individuals showed the strongest correlation between social competence and
      activation of right hemisphere structures involved in social cognitive
      processing, whereas in patients, the correlation pattern was lateralized to left
      hemisphere areas. Unaffected siblings of patients exhibited a pattern
      intermediate between the other groups. These results support the hypothesis that
      schizophrenia may be characterized by an abnormal functioning of nondominant
      hemisphere structures involved in the processing of socially salient information.

PMID- 24927686
TI  - Environmental and phylogeographical determinants of the distribution of the Old
      World screwworm fly in Indonesia.
AB  - The Old World screwworm (OWS) fly, Chrysomya bezziana, is an obligate parasite of
      livestock, and the myiasis caused by its larval infestations is economically
      important in Indonesia. The current spatial distribution of such a pest depends
      on two main factors: the current environmental conditions in which it can
      survive; and, its ability to occupy those environments by dispersal, which can be
      inferred from phylogeography and population genetics. These indicate that all OWS
      flies in Indonesia have mitochondrial cytochrome b (cyt b) haplotypes of the
      Asian lineage, and the regional separation of its four sub-lineages is the result
      of infrequent long-distance dispersal. We report the first investigation to
      associate regional cyt b sub-lineages of the OWS fly with environmental
      variables. Principal Components Analysis was used to demonstrate that these sub
      lineages are associated with very similar macro-climates throughout Indonesia.
      Then, a species distribution model for the OWS fly in Indonesia was obtained by
      using the Maxent program. This indicated that elevation captured information not
      given by other environmental variables, and cattle density provided the most
      useful information by itself. The results of our study provide some important
      leads for future research, which will require better, stratified sampling. 

PMID- 24927687
TI  - Obacunone exhibits anti-proliferative and anti-aromatase activity in vitro by
      inhibiting the p38 MAPK signaling pathway in MCF-7 human breast adenocarcinoma
      cells.
AB  - Overexpression of the aromatase enzyme CYP19 has been implicated in the onset of
      estrogen-dependent breast carcinogenesis. Obacunone, a natural compound present
      in citrus fruits, has been demonstrated for various biological activities
      including anti-cancer and anti-inflammatory properties. In the present study, we
      have isolated obacunone and obacunone glucoside (OG) from lemon seeds, then
      fractionated these compounds using chromatographic techniques and characterized
      them by HPLC, LC-MS, and 2D NMR spectral analysis. To investigate the mechanism
      of anti-cancer and anti-aromatase activities of limonoids, their cytotoxic effect
      was tested on human breast cancer (MCF-7) and non-malignant (MCF-12F) breast
      cells. MTT assays confirmed that obacunone was strongly inhibited MCF-7 cell
      proliferation without affecting non-malignant breast cells. Treatment with
      obacunone increased apoptosis by up-regulating expression of the pro-apoptotic
      protein Bax and down-regulating the anti-apoptotic protein Bcl2, as well as
      inducing G1 cell cycle arrest. In addition, obacunone significantly inhibited
      aromatase activity in an in vitro enzyme assay. Exposure of MCF-7 breast cancer
      cells to obacunone down-regulated expression of inflammatory molecules including
      nuclear factor-kappa B (NF-kappaB) and cyclooxygenase-2 (COX-2). Furthermore, we
      found that obacunone inhibited COX-2 and NF-kappaB by activation of the p38
      mitogen-activated protein kinase (MAPK). Finally, the uptake level of obacunone
      into MCF-7 cells was measured by HPLC and its structure was confirmed by LC-HR
      MS. This study demonstrated that obacunone may have the potential to prevent
      estrogen-responsive breast cancer through inhibition of the aromatase enzyme and
      inflammatory pathways, as well as activation of apoptosis. 

PMID- 24927688
TI  - Another step closer to better understanding of renal cell carcinoma - the new
      roles of alkaline phosphatase unravelled.

PMID- 24927689
TI  - Serum levels of sclerostin, Dickkopf-1, and secreted frizzled-related protein-4
      are not changed in individuals with high bone mass causing mutations in LRP5.
AB  - SUMMARY: We compared circulating levels of Wnt inhibitors among patients with
      high bone mass mutations in LRP5, unaffected kindred, and unrelated normal
      controls. Inhibitors were unchanged in affected and unaffected kindred. We saw no
      meaningful differences between controls and affected individuals. LRP5 signaling
      may not influence circulating levels of these inhibitors. INTRODUCTION: It is
      thought that gain-of-function mutations in LRP5 result in high bone mass
      syndromes because these allelic variants confer resistance to the actions of
      endogenous inhibitors of Wnt signaling. We therefore attempted to determine if
      circulating levels of Wnt inhibitors are altered in patients with gain-of
      function mutations in LRP5. METHODS: This is a cross-sectional study in a
      university research center. Serum was collected from consented volunteers known
      to have either the G171V or N198S gain-of-function mutations in LRP5, kindred
      members affected with either mutation, unrelated kindred, and unrelated normal
      age-matched controls. BMD was provided or measured on site. RESULTS: There were
      no significant differences found in the serum levels of sclerostin (SOST),
      Dickkopf-1 (Dkk-1), or secreted frizzled-related protein-4 (SFRP-4) in affected
      vs. unaffected individuals from different kindreds or when compared to age
      matched unrelated normal individuals. Mean serum SOST values in affected and
      unaffected kindred members and unrelated normal controls were 52.7 +/- 6.1, 36.5
      +/- 9.6, and 54.8 +/- 5.4, respectively. For Dkk-1, the values were 25.9 +/- 3.4,
      25.7 +/- 3.0, and 17.3 +/- 2.3 and for SFRP-4, 38.1 +/- 2.3, 39.8 +/- 3.6, and
      28.5 +/- 1.7. Serum levels of RANKL and osteoprotegerin (OPG) were not different
      in the three groups. CONCLUSIONS: Circulating levels of endogenous Wnt inhibitors
      do not change in patients with gain-of-function mutations in LRP5 including Dkk1,
      which is suppressed by Wnt signaling. It may be that circulating levels of Wnt
      inhibitors do not reflect changes in target tissues. It is also possible that
      other mechanisms besides or in addition to resistance in Wnt inhibitors explains
      the skeletal effects of these mutations.

PMID- 24927690
TI  - Roux-en Y gastric bypass is superior to duodeno-jejunal bypass in improving
      glycaemic control in Zucker diabetic fatty rats.
AB  - BACKGROUND: Whilst weight loss results in many beneficial metabolic consequences,
      the immediate improvement in glycaemia after Roux-en-Y Gastric bypass (RYGB)
      remains intriguing. Duodenal jejunal bypass (DJB) induces similar glycaemic
      effects, while not affecting calorie intake or weight loss. We studied diabetic
      ZDF(fa/fa) rats to compare the effects of DJB and RYGB operations on glycaemia.
      METHODS: Male ZDF(fa/fa) rats, aged 12 weeks underwent RYGB, DJB or sham
      operations. Unoperated ZDF(fa/fa) and ZDF(fa/+w)ere used as controls. Body
      weight, food intake, fasting glucose, insulin and gut hormones were measured at
      baseline and on postoperative days 2, 10 and 35. An oral glucose tolerance test
      (OGTT) was performed on days 12 and 26. RESULTS: DJB had similar food intake and
      body weight to sham-operated and unoperated control ZDF(fa/fa) rats (p = NS), but
      had lower fasting glucose (p < 0.05). RYGB had lower food intake, body weight and
      fasting glucose compared to all groups (p < 0.001). DJB prevented the progressive
      decline in fasting insulin observed in the sham-operated or unoperated ZDF(fa/fa)
      rats, while RYGB with normalized glycaemia reduced the physiological requirement
      for raised fasting insulin. CONCLUSIONS: Bypassing the proximal small bowel with
      the DJB has mild to moderate body weight independent effects on glucose
      homeostasis and preservation of fasting insulin levels in the medium term. These
      effects might be further amplified by the additional anatomical and physiological
      changes after RYGB.

PMID- 24927691
TI  - Caloric intake capacity as measured by a standard nutrient drink test helps to
      predict weight loss after bariatric surgery.
AB  - BACKGROUND: Instruments that enable to select individuals that will benefit most
      from bariatric surgery (BS) are necessary to increase its cost-efficiency. Our
      goal was to assess if intake capacity, measured with a standardized test,
      predicts response to BS. METHODS: Patients with criteria for BS were randomly
      allocated to laparoscopic gastric bypass (LRYGB) or sleeve gastrectomy (LSG). We
      measured caloric intake capacity before and 1 year after surgery using a
      standardized nutrient drink test. We evaluated if pre-surgery satiation could
      predict satiation and weight loss (%) 1 year after surgery using multiple
      regression modeling. Descriptive statistics are given as mean +/- SD. RESULTS:
      Fourteen women (48 +/- 9 years old, BMI 41 +/- 3 kg/m(2)) were evaluated before
      and 11 +/- 2.6 months after surgery (seven LRYGB, seven LSG). Caloric intake
      capacity diminished after surgery (-950 +/- 85 kcal on average [70 +/- 8 %
      decrease over basal intake capacity]; p=0.002) and similarly in both LRYGB (72 +/
      7 % decrease) and LSG groups (68 +/- 8 % decrease); p=0.5. There was a
      significant weight reduction after surgery (-32 +/- 10 kg [30 +/- 8 % of total
      basal weight]) with a mean post-surgery BMI of 29 +/- 2 kg/m(2). The best
      predictive model of weight loss (%) after surgery (R (2)=89 %, p=0.0009)
      included: BMI (p=0.0004), surgery type (p=0.01) and pre-surgery intake capacity
      (p=0.006). Weight loss was higher in heavier patients and those undergoing LRYGB.
      Patients with higher intake capacity had a poorer outcome independently of basal
      BMI and surgery type. CONCLUSIONS: Caloric intake capacity, as measured by a
      standard nutrient drink test, helps to predict weight loss after bariatric
      surgery. This test might be useful in algorithms of obesity treatment decision.

PMID- 24927692
TI  - Coronary calcium scores 6 years after bariatric surgery.
AB  - BACKGROUND: Obesity is associated with elevated coronary artery calcium (CAC), a
      marker of coronary atherosclerosis that is strongly predictive of cardiovascular
      events. We evaluated the effects of marked weight loss achieved through Roux-en-Y
      gastric bypass surgery (GBS) on CAC scores. METHODS: We performed
      echocardiography and computed tomography of the heart in 149 subjects 6 years
      after enrollment in a prospective registry evaluating the cardiovascular effects
      of GBS. Coronary calcium scores, left ventricular ejection fraction, and left
      ventricular mass were measured. RESULTS: At baseline, most coronary risk factors
      were similar between the GBS and nonsurgical groups including current smoking,
      systolic blood pressure, LDL-C, HDL-C, and TG. However, GBS patients were younger
      (4.7 years), less likely to be diabetic, and less likely to be postmenopausal. At
      6 years after enrollment, CAC score was significantly lower in patients who
      underwent GBS than those without surgery (p < 0.01). GBS subjects had a lower
      likelihood of having measureable coronary calcium (odds ratio of CAC > 0 = 0.39;
      95 % CI of (0.17, 0.90)). Significant predictors of 0 CAC were GBS, female
      gender, younger age, baseline BMI, and baseline LDL-C. Substituting change in BMI
      for group status as a predictor variable showed that BMI change also predicted
      CAC (p = 0.045). Changes in LDL-C did not predict the CAC differences between
      groups (p = 0.67). CONCLUSIONS: Sustained weight loss achieved through bariatric
      surgery is associated with less coronary calcification. This effect, which
      appears to be independent of changes in LDL-C, may contribute to lower cardiac
      mortality in patients with successful GBS.

PMID- 24927693
TI  - Revisional bariatric surgery following failed primary laparoscopic sleeve
      gastrectomy: a systematic review.
AB  - Revisional bariatric surgery following laparoscopic sleeve gastrectomy (LSG)
      failure presents a clinical challenge for the bariatric surgeon. Limited evidence
      exists in selecting the appropriate revisional operation: laparoscopic gastric
      bypass (LGB), laparoscopic re-sleeve gastrectomy (LRSG), or other surgical
      intervention (OSI), to address weight regain. We systematically reviewed the
      literature to assess the efficacy of existing revisional surgery. A comprehensive
      search of electronic databases (e.g., Medline, Embase, Scopus, Web of Science,
      and the Cochrane Library) was completed. All randomized controlled trials, non
      randomized comparison study, and case series were included. Eleven primary
      studies (218 patients) were identified and included in the systematic review.
      Studies were grouped into three main categories: LGB, LRSG, and OSI. Preoperative
      body mass index (BMI) was 41.9 kg/m(2) (LGB), 38.5 kg/m(2) (LRSG), and 44.4
      kg/m(2) (OSI). After conversion to LGB, BMI decreased to 33.7 and 35.7 kg/m(2) at
      12 and 24 months of follow-up, respectively. Excess weight loss (EWL) was 60 and
      48 % over the same periods. After LRSG, BMI decreased to 30.4 and 35.3 kg/m(2)
      with corresponding EWL of 68 and 44 %, at 12 and 24 months, respectively. After
      OSI, BMI decreased to 27.3 kg/m(2) with an EWL of 75 % at 24-month follow-up but
      could not be analyzed due to incomplete data collection in primary studies. Both
      LGB and LRSG achieve effective weight loss following failed LSG. The less
      technically challenging nature of LRSG may be more widely applicable. Further
      research is required to elicit sustainability in long-term weight loss benefits.

PMID- 24927695
TI  - Isolation and characterization of a thermotolerant ene reductase from Geobacillus
      sp. 30 and its heterologous expression in Rhodococcus opacus.
AB  - Rhodococcus opacus B-4 cells are adhesive to and even dispersible in water
      immiscible hydrocarbons owing to their highly lipophilic nature. In this study,
      we focused on the high operational stability of thermophilic enzymes and applied
      them to a biocatalytic conversion in an organic reaction medium using R. opacus B
      4 as a lipophilic capsule of enzymes to deliver them into the organic medium. A
      novel thermo- and organic-solvent-tolerant ene reductase, which can catalyze the
      enantioselective reduction of ketoisophorone to (6R)-levodione, was isolated from
      Geobacillus sp. 30, and the gene encoding the enzyme was heterologously expressed
      in R. opacus B-4. Another thermophilic enzyme which catalyzes NAD(+)-dependent
      dehydrogenation of cyclohexanol was identified from the gene-expression library
      of Thermus thermophilus and the gene was coexpressed in R. opacus B-4 for
      cofactor regeneration. While the recombinant cells were not viable in the mixture
      due to high reaction temperature, 634 mM of (6R)-levodione could be produced with
      an enantiopurity of 89.2 % ee by directly mixing the wet cells of the recombinant
      R. opacus with a mixture of ketoisophorone and cyclohexanol at 50  degrees C. The
      conversion rate observed with the heat-killed recombinant cells was considerably
      higher than that obtained with a cell-free enzyme solution, demonstrating that
      the accessibility between the substrates and enzymes could be improved by
      employing R. opacus cells as a lipophilic enzyme capsule. These results imply
      that a combination of thermophilic enzymes and lipophilic cells can be a
      promising approach for the biocatalytic production of water-insoluble chemicals. 

PMID- 24927696
TI  - Removal of endocrine disruptors and non-steroidal anti-inflammatory drugs through
      wastewater chlorination: the effect of pH, total suspended solids and humic acids
      and identification of degradation by-products.
AB  - Endocrine disrupting chemicals (EDCs) and non-steroidal anti-inflammatory drugs
      (NSAIDs) are two groups of emerging pollutants the significance of which rests on
      their persistent detection in the aquatic environment and their possible adverse
      effects. Wastewater treatment plants are one of the major ways for transporting
      such chemicals in the aquatic environment. Chlorination is usually the last stage
      of treatment before wastewater being disposed to the aquatic environment. This
      work focuses on the evaluation of the effect of chlorine dose and specific
      wastewater characteristics (pH, total suspended solids and humic acids) on the
      removal of target EDCs and NSAIDs through chlorination. Another objective of this
      study is the identification of chlorination by-products of specific EDCs and
      NSAIDs and their dependence on contact time. Based on the results it is concluded
      that the effect of chlorine dose and humic acids concentration on the degradation
      of target compounds during chlorination is minimal. On the contrary, pH is a
      critical parameter which highly affects process performance. Moreover, it is
      concluded that not only the free available chlorine species, but also the
      properties of EDCs and NSAIDs under different pH conditions can affect
      chlorination process performance. The effect of TSS on the degradation of the
      target compounds during chlorination is more profound for chemicals with high Kow
      values and therefore higher affinity to partition to the particulate phase (i.e.
      nonylphenols, triclosan). Several degradation by-products were identified through
      chlorination of nonylphenol, bisphenol A and diclofenac. The dependence of these
      by-products on chlorination contact time is also demonstrated. 

PMID- 24927694
TI  - Parallels between major depressive disorder and Alzheimer's disease: role of
      oxidative stress and genetic vulnerability.
AB  - The thesis of this review is that oxidative stress is the central factor in major
      depressive disorder (MDD) and Alzheimer's disease (AD). The major elements
      involved are inflammatory cytokines, the hypothalamic-pituitary axis, the
      hypothalamic-pituitary gonadal, and arginine vasopressin systems, which induce
      glucocorticoid and "oxidopamatergic" cascades when triggered by psychosocial
      stress, severe life-threatening events, and mental-affective and somatic
      diseases. In individuals with a genomic vulnerability to depression, these
      cascades may result in chronic depression-anxiety-stress spectra, resulting in
      MDD and other known depressive syndromes. In contrast, in subjects with genomic
      vulnerability to AD, oxidative stress-induced brain damage triggers specific
      antioxidant defenses, i.e., increased levels of amyloid-beta (Abeta) and
      aggregation of hyper-phosphorylated tau, resulting in paired helical filaments
      and impaired functions related to the ApoEepsilon4 isoform, leading to complex
      pathological cascades culminating in AD. Surprisingly, all the AD-associated
      molecular pathways mentioned in this review have been shown to be similar or
      analogous to those found in depression, including structural damage, i.e.,
      hippocampal and frontal cortex atrophy. Other interacting molecular signals,
      i.e., GSK-3beta, convergent survival factors (brain-derived neurotrophic factor
      and heat shock proteins), and transition redox metals are also mentioned to
      emphasize the vast array of intermediates that could interact via comparable
      mechanisms in both MDD and AD. 

PMID- 24927698
TI  - Is there a relationship between dietary MSG and [corrected] obesity in animals or
      humans?
AB  - The sodium salt of glutamate (monosodium glutamate; MSG) imparts a savory/meaty
      taste to foods, and has been used as a flavoring agent for millennia. Past
      research on MSG/glutamate has evaluated its physiologic, metabolic and behavioral
      actions, and its safety. Ingested MSG has been found to be safe, and to produce
      no remarkable effects, except on taste. However, some recent epidemiologic and
      animal studies have associated MSG use with obesity and aberrations in fat
      metabolism. Reported effects are usually attributed to direct actions of ingested
      MSG in brain. As these observations conflict with past MSG research findings, a
      symposium was convened at the 13th International Congress on Amino Acids,
      Peptides and Proteins to discuss them. The principal conclusions were: (1) the
      proposed link between MSG intake and weight gain is likely explained by co
      varying environmental factors (e.g., diet, physical activity) linked to the
      "nutrition transition" in developing Asian countries. (2) Controlled intervention
      studies adding MSG to the diet of animals and humans show no effect on body
      weight. (3) Hypotheses positing dietary MSG effects on body weight involve
      results from rodent MSG injection studies that link MSG to actions in brain not
      applicable to MSG ingestion studies. The fundamental reason is that glutamate is
      metabolically compartmentalized in the body, and generally does not passively
      cross biologic membranes. Hence, almost no ingested glutamate/MSG passes from gut
      into blood, and essentially none transits placenta from maternal to fetal
      circulation, or crosses the blood-brain barrier. Dietary MSG, therefore, does not
      gain access to brain. Overall, it appears that normal dietary MSG use is unlikely
      to influence energy intake, body weight or fat metabolism. 

PMID- 24927697
TI  - Metabolomic analysis of amino acid and energy metabolism in rats supplemented
      with chlorogenic acid.
AB  - This study was conducted to investigate effects of chlorogenic acid (CGA)
      supplementation on serum and hepatic metabolomes in rats. Rats received daily
      intragastric administration of either CGA (60 mg/kg body weight) or distilled
      water (control) for 4 weeks. Growth performance, serum biochemical profiles, and
      hepatic morphology were measured. Additionally, serum and liver tissue extracts
      were analyzed for metabolomes by high-resolution (1)H nuclear magnetic resonance
      based metabolomics and multivariate statistics. CGA did not affect rat growth
      performance, serum biochemical profiles, or hepatic morphology. However,
      supplementation with CGA decreased serum concentrations of lactate, pyruvate,
      succinate, citrate, beta-hydroxybutyrate and acetoacetate, while increasing serum
      concentrations of glycine and hepatic concentrations of glutathione. These
      results suggest that CGA supplementation results in perturbation of energy and
      amino acid metabolism in rats. We suggest that glycine and glutathione in serum
      may be useful biomarkers for biological properties of CGA on nitrogen metabolism
      in vivo. 

PMID- 24927699
TI  - A novel highly sensitive and selective fluorescent sensor for imaging copper (II)
      in living cells.
AB  - In this work, we designed and synthesized a novel quinolin-based derivative which
      exhibited signaling behaviors for Cu(2+). Upon the addition of Cu(2+) to the
      solution of the molecule, it displayed an obvious fluorescence quenching in a
      linear fashion due to the formation of a 1:1 metal-ligand complex. This
      fluorescent sensor exhibited a rare sensitivity toward Cu(II) (the level of
      magnitude could be 6 * 10(-8)), a rapid response (<10 s) and also high
      selectivity toward Cu(2+) over other metal ions such as Na(+), K(+), Ca(2+),
      Mg(2+), Ba(2+), Fe(3+), Mn(2+), Hg(2+), Pb(2+), Cd(2+), Cr(3+), Co(2+), Zn(2+)
      and Al(3+). Simultaneously, the cell imaging experiments and filter paper test
      demonstrated its extensive applicability. 

PMID- 24927700
TI  - Subgroups of Alzheimer's disease: stability of empirical clusters over time.
AB  - Although episodic memory impairment is usually the earliest sign of Alzheimer's
      disease (AD), there are up to 15% of patients presenting with early impairment in
      non-memory cognitive functions (i.e., atypical AD). Stratifying patients with AD
      may aid clinical trials. Previous studies divided patients by cognitive profile,
      focusing on cross-sectional analyses without testing stability of clusters over
      time. We used principal component analysis followed by cluster analyses in 127
      patients with AD based on 24 cognitive scores at 0, 6, 12, and 24 months follow
      up. We investigated the definition of clusters and their stability over time as
      well as interactions of cluster assignment and disease severity. At each time
      point, six distinct factors and four distinct clusters were extracted that did
      not differ substantially between time points. Clusters were defined by cognitive
      profile rather than disease severity. 85% of patients fell into the same cluster
      twice, 42% three times, and 17% four times. Subjects with focal semantic
      impairment progressed significantly faster than the other cluster.
      Longitudinally, focal deficits increased relatively rather than tending toward
      average disease severity. The observed similar cluster definitions at each time
      point indicate the validity of the approach. Cluster-specific longitudinal
      increases of focal impairments and significant between-cluster differences in
      disease progression make this approach useful for stratified inclusion into
      clinical trials. 

PMID- 24927701
TI  - Is anterior communicating artery syndrome related to fornix lesions?
AB  - Anterior communicating artery (ACoA) syndrome, which may occur after rupture of
      ACoA aneurysms, consists of anterograde memory problems, executive dysfunctions,
      confabulations, and personality changes. Recently, the employment of diffusion
      tensor tractography (DTT) has related ACoA to microstructural lesions in the
      cingulum and the fornix, but an accurate characterization of these subjects
      should be provided. We report the clinical and neuropsychological findings of a
      patient who developed a severe and persistent amnesia together with significant
      behavioral changes, as well as her imaging results, where the sole evidence of
      brain damage was that of the fornix demonstrated by DTT. The four-year
      neuropsychological follow-up of the subject allows exclusion of other causes.
      This case demonstrates that microstructural lesions of fornix may lead to
      persistent amnesia, executive impairments, and behavioral changes and contributes
      to the knowledge of its role in cognition. 

PMID- 24927702
TI  - Evaluation of whole brain health in aging and Alzheimer's disease: a standard
      procedure for scoring an MRI-based brain atrophy and lesion index.
AB  - BACKGROUND: The Brain Atrophy and Lesion Index (BALI), a semi-quantitative rating
      scale, has been developed to evaluate whole brain structural changes in aging and
      Alzheimer's disease (AD). OBJECTIVE: This study describes a standard procedure to
      score the BALI and train new raters for reliable BALI evaluation following this
      procedure. METHODS: Structural MRI of subjects in the Alzheimer's Disease
      Neuroimaging Initiative dataset who had 3.0T, T1, and T2 weighted MRI scans at
      baseline and at 6, 12, and 24 month follow-ups were retrieved (n = 122, including
      24 AD, 51 mild cognitive impairment patients, and 47 healthy control subjects).
      Images were evaluated by four raters following training with a step-by-step BALI
      process. Seven domains of structural brain changes were evaluated, and a total
      score was calculated as the sum of the sub-scores. RESULTS: New raters achieved
      >90% accuracy after two weeks of training. Reliability was shown in both intra
      rater correlation coefficients (ICC >= 0.92, p < 0.001) and inter-rater
      correlation coefficients (ICC >=0.88, p < 0.001). Mean BALI total scores differed
      by diagnosis (F >= 2.69, p <= 0.049) and increased consistently over two years.
      CONCLUSION: The BALI can be introduced using a standard procedure that allows new
      users to achieve highly reliable evaluation of structural brain changes. This can
      advance its potential as a robust method for assessing global brain health in
      aging, AD, and mild cognitive impairment.

PMID- 24927704
TI  - PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach.
AB  - Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of
      y-secretase, which is responsible for sequential proteolytic cleavages of amyloid
      precursor proteins and the subsequent formation of amyloid-beta peptides. 150 RNA
      samples from the entorhinal cortex, auditory cortex and hippocampal regions of
      individuals with Alzheimer's disease (AD) and controls elderly subjects were
      analyzed with using real-time rtPCR. There were no differences between groups for
      PSEN1 expression. PSEN2 was significantly downregulated in the auditory cortex of
      AD patients when compared to controls and when compared to other brain regions of
      the patients. Alteration in PSEN2 expression may be a risk factor for AD. 

PMID- 24927706
TI  - Nutraceuticals: a novel concept in prevention and treatment of Alzheimer's
      disease and related disorders.
AB  - Alzheimer's disease is a growing health problem worldwide. The pharmaceutical
      industry has not recently developed any new drugs that have had a significant
      impact on the natural history of the disease, so considerable attention has been
      given to nutraceuticals and nutritional bioactive compounds that can be obtained
      directly from diet or supplementation. These compounds may be able to modify
      physiopathological processes responsible for neurodegeneration and/or to have pro
      cognitive properties. Here, we review current knowledge on the role of diet
      modifications, lipid and carbohydrates consumption, vitamin supplementation, and
      the possible effects of antioxidant and nutraceutical compounds with
      neuroprotective activity, in the prevention and treatment of Alzheimer's disease
      and related disorders. 

PMID- 24927705
TI  - Positive florbetapir PET amyloid imaging in a subject with frequent cortical
      neuritic plaques and frontotemporal lobar degeneration with TDP43-positive
      inclusions.
AB  - Abnormal neuronal accumulation and modification of TAR DNA binding protein 43
      (TDP-43) have recently been discovered to be defining histopathological features
      of particular subtypes of frontotemporal dementia and amyotrophic lateral
      sclerosis, and are also common in aging, particularly coexisting with hippocampal
      sclerosis and Alzheimer's disease pathology. This case report describes a 72 year
      old Hispanic male with no family history of neurological disease, who presented
      at age 59 with obsessive behavior, anxiety, agitation, and dysphasia. Positron
      emission tomography imaging using the amyloid ligand 18F florbetapir (Amyvid) was
      positive. Postmortem examination revealed frequent diffuse and neuritic amyloid
      plaques throughout the cerebral cortex, thalamus, and striatum, Braak stage II
      neurofibrillary degeneration, and frequent frontal and temporal cortex TDP-43
      positive neurites with rare nuclear inclusions. The case is unusual and
      instructive because of the co-existence of frequent cortical and diencephalic
      amyloid plaques with extensive TDP-43-positive histopathology in the setting of
      early-onset dementia and because it demonstrates that a positive cortical amyloid
      imaging signal in a subject with dementia does not necessarily establish that
      Alzheimer's disease is the sole cause.

PMID- 24927708
TI  - The partial volume effect in the quantification of 1H magnetic resonance
      spectroscopy in Alzheimer's disease and aging.
AB  - 1H-MRS variability increases due to normal aging and also as a result of atrophy
      in grey and white matter caused by neurodegeneration. In this work, an automatic
      process was developed to integrate data from spectra and high-resolution
      anatomical images to quantify metabolites, taking into account tissue partial
      volumes within the voxel of interest avoiding additional spectra acquisitions
      required for partial volume correction. To evaluate this method, we use a cohort
      of 135 subjects (47 male and 88 female, aged between 57 and 99 years) classified
      into 4 groups: 38 healthy participants, 20 amnesic mild cognitive impairment
      patients, 22 multi-domain mild cognitive impairment patients, and 55 Alzheimer's
      disease patients. Our findings suggest that knowing the voxel composition of
      white and grey matter and cerebrospinal fluid is necessary to avoid partial
      volume variations in a single-voxel study and to decrease part of the variability
      found in metabolites quantification, particularly in those studies involving
      elder patients and neurodegenerative diseases. The proposed method facilitates
      the use of 1H-MRS techniques in statistical studies in Alzheimer's disease,
      because it provides more accurate quantitative measurements, reduces the inter
      subject variability, and improves statistical results when performing group
      comparisons. 

PMID- 24927707
TI  - Synaptophysin and synaptojanin-1 in Down syndrome are differentially affected by
      Alzheimer's disease.
AB  - Adults with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by
      40 years of age. Synaptophysin (SYN) consistently declines with age and is
      further reduced with sporadic AD. Thus, we hypothesized that SYN would be reduced
      in DS with AD. The gene for synaptojanin-1 (SYNJ1), involved in synaptic vesicle
      recycling, is on chromosome 21. We measured SYN and SYNJ1 in an autopsy series of
      39 cases with DS and 28 without DS, along with 7 sporadic AD cases. SYN was
      significantly lower in DSAD compared with DS alone and similar to sporadic AD.
      Reduced SYN is associated with AD neuropathology and with Abeta levels in DS, as
      is seen in sporadic AD. SYNJ1 was significantly higher in DS and correlated with
      several measures of Abeta. SYNJ1 was higher in DSAD and significantly higher than
      SYNJ1 in sporadic AD. Although significantly higher in DS, SYNJ1 is further
      increased with AD neuropathology suggesting interesting differences in a synapse
      associated protein that is overexpressed in trisomy 21. 

PMID- 24927709
TI  - Non-pharmacological interventions for patients with mild cognitive impairment: a
      meta-analysis of randomized controlled trials of cognition-based and exercise
      interventions.
AB  - BACKGROUND: Non-pharmacological interventions, including cognition-based
      intervention and physical exercise, are available for mild cognitive impairment
      (MCI), but their efficacy remains uncertain. OBJECTIVE: To evaluate efficacy of
      cognition-based intervention and physical exercise on cognitive domains in
      patients with MCI. METHODS: We searched MEDLINE, EMBASE, the Cochrane library,
      and BIOSIS previews to identify randomized controlled trials (RCTs) that involved
      cognition-based intervention and physical exercise for persons who were diagnosed
      with MCI. The pooled weight mean difference or standard mean difference (SMD)
      were calculated using a random-effect model. RESULTS: We found significant
      effects of cognition-based intervention on global cognitive function (SMD 0.37
      [0.07, 0.68] p = 0.02). Besides, cognition-based intervention produced
      significant effects on executive function reported with TMT-B (SMD 0.8 [0.09,
      1.5] p = 0.03) and delayed memory (SMD 0.31 [0.01, 0.61] p = 0.05). A beneficial
      improvement in global cognitive function was also seen in the exercise group
      compared to the control group (SMD 0.25 [0.08, 0.41] p = 0.003). CONCLUSIONS:
      Both of cognition-based intervention and physical exercise had the potential to
      improve global cognitive function. Weak evidence of improvements was also
      observed for the domains of executive function and delayed memory following
      cognition-based intervention. Nevertheless, future standard RCTs are still needed
      to identify the clinical value of our results.

PMID- 24927710
TI  - Early neuronal loss and axonal/presynaptic damage is associated with accelerated
      amyloid-beta accumulation in AbetaPP/PS1 Alzheimer's disease mice subiculum.
AB  - The progressive cognitive decline leading to dementia in Alzheimer's disease (AD)
      patients is the consequence of a severe loss of synapses and neurons affecting
      particular cell subpopulations in selected brain areas, with the subiculum being
      one of the earliest regions displaying severe atrophy and pathology. The lack of
      significant neuronal loss in most AD models is, in fact, the major shortcoming
      for the preclinical evaluation of drugs that could have greater potential in
      patients to alleviate or prevent this disease. In this study, using
      immunohistochemical and stereological approaches, we have analyzed the
      histopathological events in the subiculum of AbetaPP751SwedLondon/PS1M146L mice,
      a transgenic model that displays neuronal vulnerability at early ages in
      hippocampus and entorhinal cortex. Our results indicate that the subiculum is the
      earliest affected region in the hippocampus, showing a selective early loss of
      both principal neurons (28%) and SOM-positive interneurons (69%). In addition,
      our data demonstrate the existence of an early axonal and synaptic pathology,
      which may represent the beginning of the synaptic disruption and loss. These
      neurodegenerative processes occur in parallel, and closely related, with the
      onset and accelerated progression of the extracellular amyloid-beta deposition,
      thus suggesting plaques as major contributors of neuronal/axonal damage. Data
      reported here indicate that this AD model displays a selective AD-like
      neurodegenerative phenotype in highly vulnerable regions, including the
      subiculum, and therefore can be a very useful model for testing the therapeutic
      ability of potential compounds to protect neurons and ameliorate disease
      symptoms. 

PMID- 24927711
TI  - The effects of impaired cerebral circulation on Alzheimer's disease pathology:
      evidence from animal studies.
AB  - Persistent systemic hypoxia, a direct consequence of alterations in vascular
      function, can compromise the brain by increasing the risk of developing dementias
      such as Alzheimer's disease (AD). Vascular contributions to cognitive impairment
      and AD in aged individuals are common, and several vascular risk factors for AD
      are linked to hypoxia. Clinical evidence confirms that structural and functional
      changes characteristic of AD pathology also occur following hypoxic-ischemic
      events such as stroke and traumatic brain injury. Studies with transgenic and non
      transgenic mouse models reliably show that hypoxia increases the levels of
      amyloid-beta peptides that form the characteristic plaques in AD brains.
      Moreover, some studies suggest that vascular lesions also promote tau
      phosphorylation, modulate apolipoprotein E expression, and have more profound
      effects in aged animals, but additional evidence is needed to establish these
      findings. Although the mechanisms underlying hypoxia-related effects remain
      unclear, controlled animal studies continue to reveal mechanistic aspects of the
      relationship between hypoxia and AD pathology that are necessary for therapeutic
      developments. The present review summarizes evidence from rodent studies
      regarding the effects of hypoxia on AD-related pathology and evaluates its impact
      on understanding human disease.

PMID- 24927713
TI  - Hand-held medical robots.
AB  - Medical robots have evolved from autonomous systems to tele-operated platforms
      and mechanically-grounded, cooperatively-controlled robots. Whilst these
      approaches have seen both commercial and clinical success, uptake of these robots
      remains moderate because of their high cost, large physical footprint and long
      setup times. More recently, researchers have moved toward developing hand-held
      robots that are completely ungrounded and manipulated by surgeons in free space,
      in a similar manner to how conventional instruments are handled. These devices
      provide specific functions that assist the surgeon in accomplishing tasks that
      are otherwise challenging with manual manipulation. Hand-held robots have the
      advantages of being compact and easily integrated into the normal surgical
      workflow since there is typically little or no setup time. Hand-held devices can
      also have a significantly reduced cost to healthcare providers as they do not
      necessitate the complex, multi degree-of-freedom linkages that grounded robots
      require. However, the development of such devices is faced with many technical
      challenges, including miniaturization, cost and sterility, control stability,
      inertial and gravity compensation and robust instrument tracking. This review
      presents the emerging technical trends in hand-held medical robots and future
      development opportunities for promoting their wider clinical uptake. 

PMID- 24927712
TI  - Prevalence of HIV, syphilis, and other sexually transmitted infections among MSM
      from three cities in Panama.
AB  - Respondent-driven sampling (RDS) was used to conduct a biobehavioral survey among
      men who have sex with men (MSM) in three cities in the Republic of Panama. We
      estimated the prevalence of HIV, syphilis, and other sexually transmitted
      infections (STIs), sociodemographic characteristics, and sexual risk behaviors.
      Among 603 MSM recruited, RDS-adjusted seroprevalences (95 % confidence intervals)
      were: HIV-David 6.6 % (2.2-11.4 %), Panama 29.4 % (19.7-39.7 %), and Colon 32.6 %
      (18.0-47.8 %); active syphilis-David 16.0 % (8.9-24.2 %), Panama 24.7 % (16.7
      32.9 %), Colon 31.6 % (14.8-47.5 %); resolved HBV infection-David 10.0 % (4.8
      16.8 %), Panama 29.4 % (20.0-38.3 %), and Colon 40.6 % (21.9-54.4 %); herpes
      simplex virus type 2-David 38.4 % (27.9-48.9 %), Panama 62.6 % (52.8-71.0 %), and
      Colon 72.9 % (57.4-85.8 %). At least a third of MSM in each city self-identified
      as heterosexual or bisexual. HIV prevalence is concentrated among MSM. Preventive
      interventions should focus on increasing HIV and syphilis testing, and increasing
      promotion of condom awareness and use. 

PMID- 24927714
TI  - WITHDRAWN: Effect of anti-coagulant choice on cord blood processing results.

PMID- 24927715
TI  - Mechanism of mesenchymal stem cell-induced neuron recovery and anti-inflammation.
AB  - BACKGROUND AIMS: After ischemic or hemorrhagic stroke, neurons in the penumbra
      surrounding regions of irreversible injury are vulnerable to delayed but
      progressive damage as a result of ischemia and hemin-induced neurotoxicity. There
      is no effective treatment to rescue such dying neurons. Mesenchymal stem cells
      (MSCs) hold promise for rescue of these damaged neurons. In this study, we
      evaluated the efficacy and mechanism of MSC-induced neuro-regeneration and immune
      modulation. METHODS: Oxygen-glucose deprivation (OGD) was used in our study. M17
      neuronal cells were subjected to OGD stress then followed by co-culture with
      MSCs. Rescue effects were evaluated using proliferation and apoptosis assays.
      Cytokine assay and quantitative polymerase chain reaction were used to explore
      the underlying mechanism. Antibody and small molecule blocking experiments were
      also performed to further understand the mechanism. RESULTS: We showed that M17
      proliferation was significantly decreased and the rate of apoptosis increased
      after exposure to OGD. These effects could be alleviated via co-culture with
      MSCs. Tumor necrosis factor-alpha was found elevated after OGD stress and was
      back to normal levels after co-culture with MSCs. We believe these effects
      involve interleukin-6 and vascular endothelial growth factor signaling pathways.
      DISCUSSION: Our studies have shown that MSCs have anti-inflammatory properties
      and the capacity to rescue injured neurons.

PMID- 24927717
TI  - Pharmacoeconomic impact of up-front use of plerixafor for autologous stem cell
      mobilization in patients with multiple myeloma.
AB  - BACKGROUND AIMS: Stem cell collection can be a major component of overall cost of
      autologous stem cell transplantation (ASCT). Plerixafor is an effective agent for
      mobilization; however, it is often reserved for salvage therapy because of its
      high cost. We present data on the pharmacoeconomic impact of the use of
      plerixafor as an up-front mobilization in patients with multiple myeloma (MM).
      METHODS: Patients with MM who underwent ASCT between January 2008 and April 2011
      at the Mount Sinai Medical Center were reviewed retrospectively. In April 2010,
      practice changes were instituted for patients with MM to delay initiation of
      granulocyte-colony-stimulating factor (G-CSF) support from day 0 to day +5 and to
      add plerixafor to G-CSF as an up-front autologous mobilization. Targets of
      collection were 5-10 * 10(6) CD34(+) cells/kg. RESULTS: Of 50 adults with MM who
      underwent ASCT, 25 received plerixafor/filgrastim and 25 received G-CSF alone as
      an up-front mobilization. Compared with the control, plerixafor mobilization
      yielded higher CD34(+) cell content (16.1 versus 8.4 * 10(6) CD34(+) cells/kg; P
      = 0.0007) and required fewer sessions of apheresis (1.9 versus 3.1; P = 0.0001).
      In the plerixafor group, the mean number of plerixafor doses required per patient
      was 1.8. Although the overall cost of medications was higher in the plerixafor
      group, the cost for blood products and overall cost of hospitalization were
      similar between the two groups. CONCLUSIONS: Up-front use of plerixafor is an
      effective mobilization strategy in patients with MM and does not have a
      substantial pharmacoeconomic impact in overall cost of hospitalization combined
      with the apheresis procedure.

PMID- 24927716
TI  - Multi-site evaluation of the BD Stem Cell Enumeration Kit for CD34(+) cell
      enumeration on the BD FACSCanto II and BD FACSCalibur flow cytometers.
AB  - BACKGROUND AIMS: Evaluation of the BD Stem Cell Enumeration Kit was conducted at
      four clinical sites with flow cytometry CD34(+) enumeration to assess agreement
      between two investigational methods: (i) the BD FACSCanto II and BD FACSCalibur
      systems and (ii) the predicate method (Beckman Coulter StemKit and StemTrol,
      Immunotech SAS, Beckman Coulter, Marseille Cedex 9, France). METHODS: Leftover
      and delinked specimens (n = 1032) from clinical flow cytometry testing were
      analyzed on the BD FACSCanto II (n = 918) and BD FACSCalibur (n = 905) in normal
      and mobilized blood, frozen and thawed bone marrow and leucopheresis and cord
      blood anticoagulated with citrate phosphate dextrose, anticoagulant citrate
      dextrose-solution A, heparin and ethylenediaminetetraacetate, alone or in
      combination. Fresh leucopheresis analysis addressed site equivalency for sample
      preparation, testing and analysis. RESULTS: The mean relative bias showed
      agreement within predefined parameters for the BD FACSCanto II (-2.81 to 4.31 +/
      7.1) and BD FACSCalibur (-2.69 to 5.2 +/-7.9). Results are reported as absolute
      and relative differences compared with the predicate for viable CD34(+),
      percentage of CD34(+) in CD45(+) and viable CD45(+) populations (or gates). Bias
      analyses of the distribution of the predicate low, mid and high bin values were
      done using BD FACSCanto II optimal gating and BD FACSCalibur manual gating for
      viable CD34(+), percentage of CD34(+) in CD45(+) and viable CD45(+). Bias results
      from both investigational methods show agreement. Deming regression analyses
      showed a linear relationship with R(2) > 0.92 for both investigational methods.
      DISCUSSION: In conclusion, the results from both investigational methods
      demonstrated agreement and equivalence with the predicate method for enumeration
      of absolute viable CD34(+), percentage of viable CD34(+) in CD45(+) and absolute
      viable CD45(+) populations.

PMID- 24927718
TI  - Human platelet lysate is a feasible candidate to replace fetal calf serum as
      medium supplement for blood vascular and lymphatic endothelial cells.
AB  - BACKGROUND AIMS: As angiogenic and lymphangiogenic key players, endothelial cells
      (ECs) are promising candidates for vascular regenerative therapies. To culture
      ECs in vitro, fetal calf serum (FCS) is most often used. However, some critical
      aspects of FCS usage, such as possible internalization of xenogeneic proteins and
      prions, must be considered. Therefore, the aim of this project was to determine
      if human platelet lysate (hPL) is a suitable alternative to FCS as medium
      supplement for the culture of blood vascular and lymphatic endothelial cells.
      METHODS: The usability of hPL was tested by analysis of endothelial surface
      marker expression, metabolic activity and vasculogenic potential of outgrowth ECs
      (OECs), human umbilical vein ECs (HUVECs), and lymphatic ECs (LECs). RESULTS:
      Expression of EC markers CD31, VEGFR2, VE-cadherin and CD146 did not differ
      significantly between the EC types cultured in FCS or hPL. In addition, OECs,
      HUVECs and LECs formed tube-like structures on Matrigel when cultured in hPL and
      FCS. With the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid
      assays, we found that the metabolic activity of OECs and LECs was slightly
      decreased when hPL was used. However, HUVECs and LECs did not show a significant
      decrease in metabolic activity, and HUVECs showed a slightly higher activity at
      low seeding densities. CONCLUSIONS: The use of hPL on different EC types did not
      reveal any substantial negative effects on EC behavior. Thus, hPL appears to be a
      favorable candidate to replace FCS as a medium supplement in the culture of ECs.

PMID- 24927719
TI  - Interrelation between genotypes of the vitamin D receptor gene and serum sex
      hormone concentrations in the Polish elderly population: the PolSenior study.
AB  - AIM: Vitamin D co-regulates the synthesis of sex hormones. Therefore, the aim of
      this study was to determine whether the presence of certain genotypes of the
      vitamin D receptor gene (VDR) is associated with the serum levels of sex hormones
      in the elderly Polish population. MATERIALS AND METHODS: The rs10735810,
      rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum levels of
      testosterone and estradiol, as well as free estrogen index (FEI) and free
      androgen index (FAI) were evaluated in 360 women and 400 men aged 65-90years
      selected from 5695 respondents of the PolSenior survey. RESULTS: Only the
      rs1544410 VDR polymorphism was associated with the serum levels of sex hormones.
      The prevalence of rs1544410 genotypes was 38% BB, 46% Bb, and 16% bb in women and
      41% BB, 44% Bb, and 15% bb in men. In women the frequency of the B allele was
      p=0.61 and b allele q=0.39, while in men it was p=0.63 and q=0.37, respectively.
      We found significant differences in the serum testosterone level (p<0.0004) and
      FAI (p<0.0015) between the rs1544410 genotypes in women but not in men. Higher
      mean testosterone level and higher mean FAI were observed in women with a rare bb
      genotype in comparison to a common BB genotype. CONCLUSION: We hypothesize that
      in women the increase in VDR expression associated with a rare genotype of the
      rs1544410 polymorphism of this gene may be associated with an increase in
      testosterone and FAI levels.

PMID- 24927721
TI  - Meconium drug testing in multiple births in the USA.
AB  - Little is published about newborn drug testing in multiple gestations. The
      objective of this study was to review the results of meconium drug screening in
      multiple births to compare drug(s) and/or drug metabolite(s) detected. A
      retrospective analysis was conducted using data from a national reference
      laboratory and an academic medical center. The data were de-identified for the
      reference laboratory dataset. For the academic center data, a detailed chart
      review of the newborn and mother's medical record was performed on cases for
      which one or more drug(s) and/or metabolites(s) were identified and confirmed in
      meconium. Meconium was analyzed for amphetamine, methamphetamine, barbiturates,
      benzodiazepines, cannabinoid metabolites, cocaine metabolites, methadone,
      opiates, oxycodone, phencyclidine and propoxyphene. One hundred and forty-two of
      1,084 sets of twins and 2 of 20 sets of triplets had mismatched results. The
      incidence of mismatched results among the individual drug or drug classes tested
      was 0.9% (208 of 23,848 total results). For the panel of drug testing performed,
      mismatches were seen in 13% (142 of 1,084) sets of twins and 10% (2 of 20) sets
      of triplets. Barbiturates (33%), opiates (30%) and benzodiazepines (28%) were the
      most common mismatches in the national reference laboratory dataset.
      Benzodiazepines (89%) and opiates (51%) were most common in the academic medical
      center dataset with most explained by iatrogenic medications administered to one
      infant but not the other. Mismatches for cannabinoids most often occurred when
      tetrahydrocannabinol metabolites were present at a low concentration (near lower
      reporting limit) in one infant but not the other. Mismatched results of meconium
      drug testing in multiples not explainable by differences in prescribed
      medications are uncommon and most often occur when an analyte is barely above
      reporting cutoff in only one infant. Administration of iatrogenic medications to
      one infant but not the other(s) is another frequent cause of such mismatches. 

PMID- 24927720
TI  - Connectivity-based parcellation of the human frontal polar cortex.
AB  - The frontal pole corresponds to Brodmann area (BA) 10, the largest single
      architectonic area in the human frontal lobe. Generally, BA10 is thought to
      contain two or three subregions that subserve broad functions such as
      multitasking, social cognition, attention, and episodic memory. However, there is
      a substantial debate about the functional and structural heterogeneity of this
      large frontal region. Previous connectivity-based parcellation studies have
      identified two or three subregions in the human frontal pole. Here, we used
      diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy
      subjects and delineated subregions based on this connectivity. This allowed us to
      determine the correspondence of structurally based subregions with the scheme
      previously defined functionally. Three subregions could be defined in each
      subject. However, these three subregions were not spatially consistent between
      subjects. Therefore, we accepted a solution with two subregions that encompassed
      the lateral and medial frontal pole. We then examined resting-state functional
      connectivity of the two subregions and found significant differences between
      their connectivities. The medial cluster was connected to nodes of the default
      mode network, which is implicated in internally focused, self-related thought,
      and social cognition. The lateral cluster was connected to nodes of the executive
      control network, associated with directed attention and working memory. These
      findings support the concept that there are two major anatomical subregions of
      the frontal pole related to differences in functional connectivity. 

PMID- 24927722
TI  - Mixture models of nucleotide sequence evolution that account for heterogeneity in
      the substitution process across sites and across lineages.
AB  - Molecular phylogenetic studies of homologous sequences of nucleotides often
      assume that the underlying evolutionary process was globally stationary,
      reversible, and homogeneous (SRH), and that a model of evolution with one or more
      site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is
      enough to accurately model the evolution of data over the whole tree. However, an
      increasing body of data suggests that evolution under these conditions is an
      exception, rather than the norm. To address this issue, several non-SRH models of
      molecular evolution have been proposed, but they either ignore heterogeneity in
      the substitution process across sites (HAS) or assume it can be modeled
      accurately using the distribution. As an alternative to these models of
      evolution, we introduce a family of mixture models that approximate HAS without
      the assumption of an underlying predefined statistical distribution. This family
      of mixture models is combined with non-SRH models of evolution that account for
      heterogeneity in the substitution process across lineages (HAL). We also present
      two algorithms for searching model space and identifying an optimal model of
      evolution that is less likely to over- or underparameterize the data. The
      performance of the two new algorithms was evaluated using alignments of
      nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25
      tipped tree. The algorithms were found to be very successful, identifying the
      correct HAL model with a 75% success rate (the average success rate for assigning
      rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model,
      identifying the correct HAS model with a 98% success rate. Finally, parameter
      estimates obtained under the correct HAL-HAS model were found to be accurate and
      precise. The merits of our new algorithms were illustrated with an analysis of 42
      337 second codon sites extracted from a concatenation of 106 alignments of
      orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S.
      paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus,
      and Candida albicans. Our results show that second codon sites in the ancestral
      genome of these species contained 49.1% invariable sites, 39.6% variable sites
      belonging to one rate category (V1), and 11.3% variable sites belonging to a
      second rate category (V2). The ancestral nucleotide content was found to differ
      markedly across these three sets of sites, and the evolutionary processes
      operating at the variable sites were found to be non-SRH and best modeled by a
      combination of eight edge-specific rate matrices (four for V1 and four for V2).
      The number of substitutions per site at the variable sites also differed
      markedly, with sites belonging to V1 evolving slower than those belonging to V2
      along the lineages separating the seven species of Saccharomyces. Finally, sites
      belonging to V1 appeared to have ceased evolving along the lineages separating S.
      cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying
      that they might have become so selectively constrained that they could be
      considered invariable sites in these species.

PMID- 24927723
TI  - Pharmacological management of pain in Australian Aged Care Facilities.
AB  - BACKGROUND: up to 80% of residents in aged care facilities (ACFs) experience
      pain, and previous studies have found that older patients with pain are often
      undertreated. Few studies have been conducted in Australia evaluating the use of
      analgesic therapy in ACF residents. OBJECTIVE: to explore the use of analgesics
      among ACF residents, including independent predictors of analgesic use, evaluate
      analgesic use against pain management guidelines and identify potential
      medication management issues. METHODS: a retrospective analysis of 7,309
      medicines reviews conducted on Australian ACF residents was undertaken.
      Medication use was compared with published guidelines relating to the management
      of pain in elderly patients or ACF residents. Multiple variable logistic
      regression was used to identify independent predictors of analgesic use. RESULTS:
      nearly 91% of residents were prescribed analgesics. Of those, 2,057 residents
      were taking regular opioids (28.1%). Only 50% of those taking regular opioids
      received regular paracetamol at doses of 3-4 g/day. The concurrent use of
      sedatives was high, with 48.4% of those taking regular opioids also taking an
      anxiolytic/hypnotic. CONCLUSION: there is a need to optimise the prescribing and
      administration of regular paracetamol as a first line and continuing therapy for
      pain management in ACF residents, to potentially improve pain management and
      reduce opioid requirements. Furthermore, with the risk of falls and fractures
      increased by concurrent use of opioids and sedatives, the widespread use of these
      drugs in a population already at high risk was concerning, indicating a need for
      better education of health professionals in this area.

PMID- 24927724
TI  - Motivators for women to attend cervical screening: the influential role of GPs.
AB  - BACKGROUND: Participation in organized cervical cancer screening has declined
      recently. While research has focussed on barriers to screening participation,
      less attention has been paid to what motivates women to attend. Moreover, little
      is known about health care provider/practitioner-level barriers and facilitators
      to participation. Better understanding of these issues could help inform
      strategies to improve participation. OBJECTIVES: To explore the role of GPs in
      influencing women's cervical screening behaviours and investigate other
      motivators for women to attend for a cervical smear. METHODS: Ten focus groups
      were conducted in Ireland, shortly before the launch of a national cervical
      screening programme. Discussions were audio-recorded, transcribed verbatim and
      transcripts were analysed thematically. RESULTS: GPs greatly influence women's
      screening behaviours and can have a positive or negative impact on women's
      participation in screening. Four major subthemes emerged in relation to this: the
      attitude of the GP; prompting by the GP; trust in the GP and women's
      relationships with their GP. Two main motivators to screening participation were
      identified: personal reasons/benefits (e.g. potential of smears to be life
      saving); and practical issues/convenience. Women's also expressed desires for
      what they would like to see incorporated in the national screening programme
      (e.g. an 'out-of-hours' service). CONCLUSION: GPs can impact positively and
      negatively on women's cervical screening participation. Providing on-going
      support to GPs around their cervical screening practices is essential to maximize
      screening attendance. Targeted information materials that focus on the personal
      reasons and benefits of having smear tests could help stimulate women to
      participate.

PMID- 24927725
TI  - Factors associated with adherence to glaucoma pharmacotherapy in the primary care
      setting.
AB  - BACKGROUND: Primary open-angle glaucoma is a leading cause of irreversible
      blindness. OBJECTIVES: To identify factors associated with adherence to glaucoma
      pharmacotherapy in the primary care setting, focusing on physicians' role.
      METHODS: Patients were recruited from primary care clinics and telephone
      interviewed using a structured questionnaire that addressed patient-, medication
      , environment- and physicians-related factors. Patients' data on pharmacy claims
      were retrieved to calculate the medication possession ratio for measuring
      adherence. RESULTS: Seven hundred thirty-eight glaucoma patients were
      interviewed. The multivariate analysis identified eight variables that were
      associated independently with adherence. Barriers to adherence were found to be
      low income, believing that 'It makes no difference to my vision whether I take
      the drops or not' and relying on someone else for drop instillation (exp(B) =
      1.91, P = 0.002; exp(B) = 2.61, P < 0.0001; exp(B) = 2.17, P = 0.001,
      respectively). Older age, having a glaucoma patient among close acquaintances,
      taking a higher number of drops per day, taking a prostaglandin drug and
      reporting that the ophthalmologist had discussed the importance of taking eye
      drops as prescribed, were found to promote adherence (exp(B) = 0.96, P < 0.0001;
      exp(B) = 0.54, P = 0.014; exp(B) = 0.81, P = 0.001; exp(B) = 0.37, P < 0.0001;
      exp(B) = 0.60, P = 0.034, respectively). No association was found between the
      patient's relationship with the family physician and adherence to glaucoma
      treatment. CONCLUSION: Adherence to glaucoma pharmacotherapy is associated with
      patient-related, medication-related, physician-related and environmental factors.
      Ophthalmologists have a significant role in promoting adherence. However, the
      potential role of family physicians is unfulfilled and unrecognized.

PMID- 24927726
TI  - Ionizing radiation affects the expression of Toll-like receptors 2 and 4 in human
      monocytic cells through c-Jun N-terminal kinase activation.
AB  - Pattern recognition receptors recognize pathogen-associated molecular patterns.
      Among these, Toll-like receptors (TLRs) have well-characterized roles in
      antibacterial and antiviral immunity. In the present study, the effects of
      ionizing radiation on the expression of TLRs and cellular responses to ligands
      were investigated in THP1 monocytes (human monocytic leukemia cells) and THP1
      derived macrophage cells (macrophage-like cells), which are induced by culturing
      in the presence of phorbol 12-myristate 13-acetate. TLR2 and TLR4 expression was
      detected in THP1 and macrophage-like cells. X-irradiation caused increased
      expression of these TLRs in THP1 and decreased expression in macrophage-like
      cells. Responses to FSL-1 (TLR2 ligand) and lipopolysaccharide (LPS, TLR4 ligand)
      were estimated by determining the induction of tumor necrosis factor-alpha (TNF
      alpha). After FSL-1 or LPS stimulation, TNF-alpha induction was greater in X
      irradiated THP1 monocytes than in non-irradiated cells. However, although TNF
      alpha expression was not affected by X-irradiation in macrophage-like cells, the
      expression of LPS-inducible interferon-beta was lower following X-irradiation of
      macrophage-like cells. To clarify the mechanisms of TLR2 and TLR4 regulation by X
      irradiation, expression of mitogen-activated protein kinase was investigated.
      These experiments showed that c-Jun N-terminal kinase (JNK) mediated increases in
      TLR expression in X-irradiated THP1 monocytes and decreases in TLR expression in
      X-irradiated macrophage-like cells. This study demonstrates that ionizing
      radiation modulates ligand-responsive TLR expression through the JNK pathway,
      depending on differentiation state. 

PMID- 24927727
TI  - Dosimetric comparison of three different treatment modalities for total scalp
      irradiation: the conventional lateral photon-electron technique, helical
      tomotherapy, and volumetric-modulated arc therapy.
AB  - The aim of this study was to compare lateral photon-electron (LPE), helical
      tomotherapy (HT), and volumetric-modulated arc therapy (VMAT) plans for total
      scalp irradiation. We selected a single adult model case and compared the
      dosimetric results for the three plans. All plans mainly used 6-MV photon beams,
      and the prescription dose was 60 Gy in 30 fractions. First, we compared the LPE,
      HT and VMAT plans, with all plans including a 1-cm bolus. We also compared HT
      plans with and without the bolus. The conformity indices for LPE, HT and VMAT
      were 1.73, 1.35 and 1.49, respectively. The HT plan showed the best conformity
      and the LPE plan showed the worst. However, the plans had similar homogeneity
      indexes. The dose to the hippocampus was the highest in the VMAT plan, with a
      mean of 6.7 Gy, compared with 3.5 Gy in the LPE plan and 4.8 Gy in the HT plan.
      The doses to the optical structures were all within the clinically acceptable
      range. The beam-on time and monitor units were highest in the HT plan. The HT
      plans with and without a bolus showed similar target coverage and organ-at-risk
      (OAR) sparing. The HT plan showed the best target coverage and conformity, with
      low doses to the brain and hippocampus. This plan also had the advantage of not
      necessarily requiring a bolus. Although the VMAT plan showed better conformity
      than the LPE plan and acceptable OAR sparing, the dose to the hippocampus should
      be considered when high doses are prescribed.

PMID- 24927728
TI  - Hsp90 modulates PPARgamma activity in a mouse model of nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent complication of
      obesity, yet cellular mechanisms that lead to its development are not well
      defined. Previously, we have documented hepatic steatosis in mice carrying a
      mutation in the Sec61a1 gene. Here we examined the mechanism behind NAFLD in
      Sec61a1 mutant mice. Livers of mutant mice exhibited upregulation of Pparg and
      its target genes Cd36, Cidec, and Lpl, correlating with increased uptake of fatty
      acid. Interestingly, these mice also displayed activation of the heat shock
      response (HSR), with elevated levels of heat shock protein (Hsp) 70, Hsp90, and
      heat shock factor 1. In cell lines, inhibition of Hsp90 function reduced
      Ppargamma signaling and protein levels. Conversely, overexpression of Hsp90
      increased Ppargamma signaling and protein levels by reducing degradation. This
      may occur via a physical interaction as Hsp90 and Ppargamma coimmunoprecipitated
      in vivo. Furthermore, inhibition of Hsp90 in Sec61a1 mutant hepatocytes also
      reduced Ppargamma protein levels and signaling. Finally, overexpression of Hsp90
      in liver cell lines increased neutral lipid accumulation, and this accumulation
      was blocked by Hsp90 inhibition. Our results show that the HSR and Hsp90 play an
      important role in the development of NAFLD, opening new avenues for the
      prevention and treatment of this highly prevalent disease. 

PMID- 24927730
TI  - Influence of coronary vessel dominance on short- and long-term outcome in
      patients after ST-segment elevation myocardial infarction.
AB  - AIMS: Prognostic importance of coronary vessel dominance in patients with ST
      elevation myocardial infarction (STEMI) remains uncertain. The aim of this study
      was to assess influence of coronary vessel dominance on the short- and long-term
      outcome after STEMI. METHODS AND RESULTS: Coronary angiographic images of
      consecutive patients presenting with first STEMI were retrospectively reviewed to
      assess coronary vessel dominance. Patients were followed after STEMI during a
      median period of 48 (IQR38-61) months for the occurrence of all-cause mortality
      and the composite of reinfarction and cardiac death. The population comprised
      1131 patients of which 971 (86%) patients had a right dominant, 102 (9%) a left
      dominant, and 58 (5%) a balanced system. After 5 years of follow-up, the
      cumulative incidence of all-cause mortality was significantly higher in patients
      with a left dominant system, compared with a right dominant and balanced system
      (log-rank P = 0.013). Moreover, a left dominant system was an independent
      predictor for 30-day mortality (OR 2.51, 95% CI 1.11-5.67, P = 0.027) and the
      composite of reinfarction and cardiac death within 30-days after STEMI (OR 2.25,
      95% CI 1.09-4.61, P = 0.028). In patients surviving first 30-days post-STEMI,
      coronary vessel dominance had no influence on long-term outcome. CONCLUSIONS: A
      left dominant coronary artery system is associated with a significantly increased
      risk of 30-day mortality and early reinfarction after STEMI. After surviving the
      first 30-days post-STEMI, coronary vessel dominance had no influence on long-term
      outcome.

PMID- 24927729
TI  - Structural characterization of human cholesterol 7alpha-hydroxylase.
AB  - Hepatic conversion to bile acids is a major elimination route for cholesterol in
      mammals. CYP7A1 catalyzes the first and rate-limiting step in classic bile acid
      biosynthesis, converting cholesterol to 7alpha-hydroxycholesterol. To identify
      the structural determinants that govern the stereospecific hydroxylation of
      cholesterol, we solved the crystal structure of CYP7A1 in the ligand-free state.
      The structure-based mutation T104L in the B' helix, corresponding to the nonpolar
      residue of CYP7B1, was used to obtain crystals of complexes with cholest-4-en-3
      one and with cholesterol oxidation product 7-ketocholesterol (7KCh). The
      structures reveal a motif of residues that promote cholest-4-en-3-one binding
      parallel to the heme, thus positioning the C7 atom for hydroxylation. Additional
      regions of the binding cavity (most distant from the access channel) are involved
      to accommodate the elongated conformation of the aliphatic side chain. Structural
      complex with 7KCh shows an active site rigidity and provides an explanation for
      its inhibitory effect. Based on our previously published data, we proposed a
      model of cholesterol abstraction from the membrane by CYP7A1 for metabolism.
      CYP7A1 structural data provide a molecular basis for understanding of the
      diversity of 7alpha-hydroxylases, on the one hand, and cholesterol-metabolizing
      enzymes adapted for their specific activity, on the other hand. 

PMID- 24927731
TI  - Iron deficiency defined as depleted iron stores accompanied by unmet cellular
      iron requirements identifies patients at the highest risk of death after an
      episode of acute heart failure.
AB  - AIM: Acute heart failure (AHF) critically deranges haemodynamic and metabolic
      homoeostasis. Iron is a key micronutrient for homoeostasis maintenance. We
      hypothesized that iron deficiency (ID) defined as depleted iron stores
      accompanied by unmet cellular iron requirements would in this setting predict the
      poor outcome. METHODS AND RESULTS: Among 165 AHF patients (age 65 +/- 12 years,
      81% men, 31% de novo HF), for ID diagnosis we prospectively applied: low serum
      hepcidin reflecting depleted iron stores (<14.5 ng/mL, the 5th percentile in
      healthy peers), and high-serum soluble transferrin receptor (sTfR) reflecting
      unmet cellular iron requirements (>=1.59 mg/L, the 95th percentile in healthy
      peers). Concomitance of low hepcidin and high sTfR (the most profound ID) was
      found in 37%, isolated either high sTfR or low hepcidin was found in 29 and 9% of
      patients, and 25% of subjects demonstrated preserved iron status. Patients with
      low hepcidin and high sTfR had peripheral oedema, high NT-proBNP, high uric acid,
      low haemoglobin (P < 0.05), and 5% in-hospital mortality (0% in remaining
      patients). During the 12-month follow-up, 33 (20%) patients died. Those with low
      hepcidin and high sTfR had the highest 12-month mortality [(41% (95% CI: 29-53%)]
      when compared with those with isolated high sTfR [15% (5-25%)], isolated low
      hepcidin [7% (0-19%)] and preserved iron status (0%) (P < 0.001). Analogous
      mortality patterns were seen separately in anaemics and non-anaemics. CONCLUSION:
      Iron deficiency defined as depleted body iron stores and unmet cellular iron
      requirements is common in AHF, and identifies those with the poor outcome. Its
      correction may be an attractive therapeutic approach.

PMID- 24927732
TI  - Lifetime and current prevalence of common DSM-IV mental disorders, their
      demographic correlates, and association with service utilisation and disability
      in older Australian adults.
AB  - OBJECTIVE: To describe lifetime and 12 month prevalence of common DSM-IV mental
      disorders, their demographic correlates, and association with service utilisation
      and disability in Australians aged 65-85 years of age. METHODS: The sample
      included Australian residents aged 65-85 years who participated in the 2007
      Australian National Survey of Mental Health and Well-being (n=1905). The
      prevalence of DSM-IV mental disorders was estimated using the lay-interviewer
      administered World Mental Health version of the Composite International
      Diagnostic Interview. RESULTS: Eight percent had experienced an affective
      disorder, 10% an anxiety disorder, and 12% a substance use disorder at some point
      in their life. Sex, age, and marital status were significant correlates of any
      lifetime mental disorder. Approximately, 2%, 4%, and 1% of old age respondents
      met criteria for mood, anxiety, and substance use disorders in the past 12
      months, respectively. The presence of physical disorder, disability, and greater
      treatment service use were associated with any mental disorder in the past 12
      months. Prevalence of lifetime and 12 month disorders by age band revealed a
      decrease as age increased. CONCLUSIONS: A substantial number of community
      dwelling old age Australians have experienced a mental disorder in their
      lifetime. Demographic correlates of mental disorder were relatively consistent
      between lifetime and 12 month prevalence of disorders, although sex made less of
      an impact and the presence of physical disorders more of an impact in recent
      disorders. Twelve month prevalence data suggest that a high proportion of old age
      Australians still experience mental disorders, predominantly anxiety and major
      depression.

PMID- 24927733
TI  - Continuation of clozapine in a patient with lymphoma.

PMID- 24927734
TI  - Longitudinal trends in the dispensing of psychotropic medications in Australia
      from 2009-2012: focus on children, adolescents and prescriber specialty.
AB  - OBJECTIVE: Longitudinal trends in the dispensing of antidepressant, antipsychotic
      and ADHD medications from 2009-2012 were examined according to age and gender of
      patient and prescriber speciality. Of particular interest were changing trends in
      the prescription of psychotropic medications to children, adolescents and young
      adults. METHOD: Dispensing data for government-subsidised antidepressant,
      antipsychotic and ADHD medications were obtained from the database maintained by
      the Department of Human Services. Results were expressed in terms of number of
      prescriptions dispensed. RESULTS: Over the four- year study period, the
      dispensing of antidepressants, antipsychotics and ADHD medications showed overall
      increases of 16.1%, 22.7% and 26.1% respectively. The most rapid percentage
      increases in antidepressant and antipsychotic dispensing occurred in children
      aged 10-14 (35.5% and 49.1% respectively), while ADHD medication dispensing rose
      most rapidly in those aged 20-24 (70.9%). Dispensing to males was more common
      during childhood for all investigated classes while two-thirds of adult
      antidepressant prescribing was to female patients. The most commonly prescribed
      antidepressants varied by age and were as follows: fluoxetine (3-19 year olds),
      desvenlafaxine (20-24 years) and venlafaxine (>25 years). Risperidone was the
      most common antipsychotic dispensed to children under 15, quetiapine to
      adolescents and young adults (15-24 years), and olanzapine to adults.
      Methylphenidate was the most common ADHD medication in those aged under 25, and
      dexamphetamine the most common in adults. Most antidepressants and antipsychotics
      were prescribed by GPs (89.9% and 70.6% respectively), while the majority of ADHD
      medications were prescribed by paediatricians (59.1%). CONCLUSIONS: Dispensing of
      psychotropic medications increased markedly from 2009 to 2012, with notable age
      specific trends. General adherence to treatment guidelines is apparent, yet
      concerns exist regarding rapid increases in serotonin noradrenaline reuptake
      inhibitor (SNRI) antidepressant prescribing, the likely overmedication of persons
      with mild psychological distress, and the increasing use of powerful psychotropic
      medications in younger populations despite uncertain risk-benefit profiles.

PMID- 24927735
TI  - The recovery model and anorexia nervosa.
AB  - OBJECTIVE: Treatments in anorexia nervosa (AN) have not been wholly effective
      and, accordingly, practices need to be reviewed. The recovery model is an
      approach to treatment that has become a guiding principle for mental health
      policy worldwide that might provide promise for AN treatment. The model has
      received much attention in recent years; however, there is a dearth of literature
      exploring how useful this model is for AN. The aim of the current article was to
      consider the relevance of this model in AN. METHODS: This article provides a
      summary of the recovery model and reviews the literature to establish whether it
      is compatible with AN. The possible utility of the approach in AN is explored and
      suggestions are made as to how the model might be implemented in treatment.
      RESULTS: Qualitative studies examining the patient's perspective of AN support
      the recovery model. Many evidenced-based treatments currently used in AN have
      elements that are consistent with a recovery model approach. Treatments that are
      most consistent with recovery approaches have been effective for those with
      chronic AN. CONCLUSION: It is proposed that the model might offer a way in which
      to add to current practice and might have particular relevance for those with
      chronic AN. Future research is required to better understand how the model can
      best be utilised in AN.

PMID- 24927737
TI  - Novel genetic associations with serum level metabolites identified by phenotype
      set enrichment analyses.
AB  - Availability of standardized metabolite panels and genome-wide single-nucleotide
      polymorphism data endorse the comprehensive analysis of gene-metabolite
      association. Currently, many studies use genome-wide association analysis to
      investigate the genetic effects on single metabolites (mGWAS) separately. Such
      studies have identified several loci that are associated not only with one but
      with multiple metabolites, facilitated by the fact that metabolite panels often
      include metabolites of the same or related pathways. Strategies that analyse
      several phenotypes in a combined way were shown to be able to detect additional
      genetic loci. One of those methods is the phenotype set enrichment analysis
      (PSEA) that tests sets of metabolites for enrichment at genes. Here we applied
      PSEA on two different panels of serum metabolites together with genome-wide data.
      All analyses were performed as a two-step identification-validation approach,
      using data from the population-based KORA cohort and the TwinsUK study. In
      addition to confirming genes that were already known from mGWAS, we were able to
      identify and validate 12 new genes. Knowledge about gene function was supported
      by the enriched metabolite sets. For loci with unknown gene functions, the
      results suggest a function that is interrelated with the metabolites, and hint at
      the underlying pathways. 

PMID- 24927739
TI  - The Westgate Service and Related Referral, Assessment, and Treatment Processes.
AB  - The formerly named "Dangerous and Severe Personality Disorder" (DSPD) units are
      no longer standalone services within the criminal justice system in England and
      Wales. These sites now provide personality disorder treatment services in the
      high-security prison estate as part of the new national Offender Personality
      Disorder (OPD) Pathway Strategy. The OPD Pathway intends to take responsibility
      for the assessment, treatment, and management of offenders who are likely to have
      a personality disorder and who present a high risk of re-offending (men and
      women) and serious harm to others (men). Further PD treatment and progression
      services are being commissioned in lower security prisons and in the community as
      part of the new PD Strategy. While the suitability criteria for the two male high
      security PD treatment sites are the same, the individual units have their own
      assessment and treatment methods. This article aims to communicate the referral,
      assessment, and treatment methods employed within the prison-based Westgate
      Personality Disorder Treatment Service, HMP Frankland. 

PMID- 24927738
TI  - Grasping nettles: cellular heterogeneity and other confounders in epigenome-wide
      association studies.
AB  - Platform technologies for measurement of CpG methylation at multiple loci across
      the genome have made ambitious epigenome-wide association studies affordable and
      practicable. In contrast to genetic studies, which estimate the effects of
      structural changes in DNA, and transcriptomic studies, which measure genomic
      outputs, epigenetic studies can access states of regulation of genome function in
      particular cells and in response to specific stimuli. Although many factors
      complicate the interpretation of epigenetic variation in human disease, cell
      specific methylation patterns and the cellular heterogeneity present in
      peripheral blood and tissue biopsies are anticipated to cause the most problems.
      In this review, we suggest that the difficulties may be exaggerated and we
      explore how cellular heterogeneity may be embraced with appropriate study designs
      and analytical tools. We further suggest that systematic mapping of the loci
      influenced by age, sex and genetic polymorphisms will bring important biological
      insights as well as improved control of epigenome-wide association studies. 

PMID- 24927740
TI  - Improving Agreement About Intervention Plans in Probation by Decision Support.
AB  - Reliability in decision making about intervention plans is a necessary condition
      for evidence-based probation work and equal treatment of offenders. Structuring
      decision making can improve agreement between clinical decision makers. In a
      former study however, we found that in Dutch probation practice structured risk
      and needs assessment did not result in acceptable agreement about intervention
      plans. The Dutch probation services subsequently introduced a tool for support in
      decision making on intervention plans. This article addresses the question
      whether the use of this tool results in better agreement between probation
      officers. A significant and meaningful improvement in agreement was found on all
      domains of the intervention plan. Implications for probation practice are
      discussed. 

PMID- 24927741
TI  - Examining the Direct and Indirect Effects of Fear and Anger on Criminal Decision
      Making Among Known Offenders.
AB  - Deterrence represents the central theoretical core of the American criminal
      justice system, yet relatively little attention has been paid to how emotions
      like fear and anger may relate to deterrence. Psychological research has debated
      whether negative emotions each have similar impacts on decision making (valence
      approaches) or if distinct emotions have unique impacts (appraisal tendency
      approaches). This study explores the direct and indirect influences of fear and
      anger on hypothetical drunk driving likelihood, including their impact on cost
      perceptions. Surveys were administered to 1,013 male and female incarcerated
      felony offenders in the Southwestern United States. Using a multivariate path
      model and controlling for a number of other individual factors, current fear
      related to increased cost perceptions and anger to decreased costs. Anger also
      maintained a direct influence on drunk driving, whereas fear did not. Despite
      their shared negative valence, fear and anger appear to have dissimilar
      influences on cost perceptions and criminal decision making. A better
      understanding of these processes may lead to improved crime prevention
      approaches. 

PMID- 24927742
TI  - Reliability and Validity of the Chinese Version of the LSI-R With Probationers.
AB  - The Level of Service Inventory-Revised (LSI-R) is an instrument used world-wide
      for offender risk/need assessment, and the predominant samples for the LSI-R
      literature were Caucasian participants. This study is the first attempt to
      examine the reliability and validity of a Chinese version of the LSI-R with 305
      probationers (269 males, 36 females) in Guangzhou, China. Factor analysis was
      conducted using principal component analysis. The internal consistency was
      estimated by Cronbach's alpha for the total and subscales. Under the cross
      sectional design, technical violation (TV) was used as a dependent variable for
      bivariate correlations and binary logistic regression model to investigate the
      concurrent validity of the Chinese version of LSI-R, controlling the age. Results
      offered support to this instrument by sound internal consistency. Significant
      gender differences were apparent on the total scores, and subscales of Criminal
      History, Family/Marital, and Companions. Bivariate correlations and binary
      logistic regression analyses supported the concurrent validity of the LSI-R total
      score for technical violations, and the subscales of Criminal History and
      Education/Employment were significantly associated with technical violations,
      which are consistent with the LSI-R literature. Overall, the LSI-R, which has
      been translated into Chinese, is a reliable risk/need assessment instrument for
      technical violations for probationers in Guangzhou, China. Further studies with
      follow-up data for different offender groups are needed. Discussions about the
      results, implications, limitations, and further research were presented. 

PMID- 24927743
TI  - Clinicians in management: a qualitative study of managers' use of influence
      strategies in hospitals.
AB  - BACKGROUND: Combining a professional and managerial role can be challenging for
      doctors and nurses. We aimed to explore influence strategies used by doctors and
      nurses who are managers in hospitals with a model of unitary and profession
      neutral management at all levels. METHODS: We did a study based on data from
      interviews and observations of 30 managers with a clinical background in
      Norwegian hospitals. RESULTS: Managers with a nursing background argued that
      medical doctors could more easily gain support for their views. Nurses reported
      deliberately not disclosing their professional background, and could use a doctor
      as their agent to achieve a strategic advantage. Doctors believed that they had
      to use their power as experts to influence peers. Doctors attempted to be medical
      role models, while nurses spoke of being a role model in more general terms.
      Managers who were not able to influence the system directly found informal
      workarounds. We did not identify horizontal strategies in the observations and
      accounts given by the managers in our study. CONCLUSIONS: Managers' professional
      background may be both a resource and constraint, and also determine the
      influence strategies they use. Professional roles and influence strategies should
      be a theme in leadership development programs for health professionals.

PMID- 24927736
TI  - Genetic variation in mitotic regulatory pathway genes is associated with breast
      tumor grade.
AB  - Mitotic index is an important component of histologic grade and has an etiologic
      role in breast tumorigenesis. Several small candidate gene studies have reported
      associations between variation in mitotic genes and breast cancer risk. We
      measured associations between 2156 single nucleotide polymorphisms (SNPs) from
      194 mitotic genes and breast cancer risk, overall and by histologic grade, in the
      Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42
      106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence
      interval (CI) 1.16-1.33, P = 4.2 * 10(-10)) and EIF3H (rs799890: OR = 1.07, 95%
      CI 1.04-1.11, P = 8.7 * 10(-6)) were significantly associated with risk of low
      grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI
      1.07-1.23, P = 7.9 * 10(-5)) after adjustment for breast cancer risk SNPs in the
      nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide
      significant genetic risk locus for low-grade breast cancer. While no SNPs were
      individually associated with high-grade disease, a pathway-level gene set
      analysis showed that variation across the 194 mitotic genes was associated with
      high-grade breast cancer risk (P = 2.1 * 10(-3)). These observations will provide
      insight into the contribution of mitotic defects to histological grade and the
      etiology of breast cancer. 

PMID- 24927744
TI  - Can authorities appreciably enhance the prescribing of oral generic risperidone
      to conserve resources? Findings from across Europe and their implications.
AB  - BACKGROUND: Generic atypical antipsychotic drugs offer health authorities
      opportunities for considerable savings. However, schizophrenia and bipolar
      disorders are complex diseases that require tailored treatments. Consequently,
      generally there have been limited demand-side measures by health authorities to
      encourage the preferential prescribing of generics. This is unlike the situation
      with hypertension, hypercholaesterolaemia or acid-related stomach disorders.The
      objectives of this study were to compare the effect of the limited demand-side
      measures in Western European countries and regions on the subsequent prescribing
      of risperidone following generics; to utilise the findings to provide future
      guidance to health authorities; and where possible, to investigate the
      utilisation of generic versus originator risperidone and the prices for generic
      risperidone. METHODS: Principally, this was a segmented regression analysis of
      retrospective time-series data of the effect of the various initiatives in
      Belgium, Ireland, Scotland and Sweden following the introduction of generic
      risperidone. The study included patients prescribed at least one atypical
      antipsychotic drug up to 20 months before and up to 20 months after generic
      risperidone. In addition, retrospective observational studies were carried out in
      Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary
      care organisation (Bury Primary Care Trust (PCT)). RESULTS: There was a
      consistent steady reduction in risperidone as a percentage of total selected
      atypical antipsychotic utilisation following generics. A similar pattern was seen
      in Austria and Spain, with stable utilisation in one English PCT. However, there
      was considerable variation in the utilisation of generic risperidone, ranging
      from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the
      price of generic risperidone varied considerably. In Scotland, generic
      risperidone was only 16% of pre-patent loss prices versus 72% in Ireland.
      CONCLUSION: Consistent findings of no increased prescribing of risperidone post
      generics with limited specific demand-side measures suggests no 'spillover'
      effect from one class to another encouraging the preferential prescribing of
      generic atypical antipsychotic drugs. This is exacerbated by the complexity of
      the disease area and differences in the side-effects between treatments. There
      appeared to be no clinical issues with generic risperidone, and prices inversely
      reflected measures to enhance their utilisation.

PMID- 24927745
TI  - Mobile health for non-communicable diseases in Sub-Saharan Africa: a systematic
      review of the literature and strategic framework for research.
AB  - BACKGROUND: Mobile health (mHealth) approaches for non-communicable disease (NCD)
      care seem particularly applicable to sub-Saharan Africa given the penetration of
      mobile phones in the region. The evidence to support its implementation has not
      been critically reviewed. METHODS: We systematically searched PubMed, Embase, Web
      of Science, Cochrane Central Register of Clinical Trials, a number of other
      databases, and grey literature for studies reported between 1992 and 2012
      published in English or with an English abstract available. We extracted data
      using a standard form in accordance with Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines. RESULTS: Our search yielded 475 citations
      of which eleven were reviewed in full after applying exclusion criteria. Five of
      those studies met the inclusion criteria of using a mobile phone for non
      communicable disease care in sub-Saharan Africa. Most studies lacked comparator
      arms, clinical endpoints, or were of short duration. mHealth for NCDs in sub
      Saharan Africa appears feasible for follow-up and retention of patients, can
      support peer support networks, and uses a variety of mHealth modalities. Whether
      mHealth is associated with any adverse effect has not been systematically
      studied. Only a small number of mHealth strategies for NCDs have been studied in
      sub-Saharan Africa. CONCLUSIONS: There is insufficient evidence to support the
      effectiveness of mHealth for NCD care in sub-Saharan Africa. We present a
      framework for cataloging evidence on mHealth strategies that incorporates health
      system challenges and stages of NCD care. This framework can guide approaches to
      fill evidence gaps in this area. Systematic review registration: PROSPERO
      CRD42014007527.

PMID- 24927746
TI  - Suicidal behaviour across the African continent: a review of the literature.
AB  - BACKGROUND: Suicide is a major cause of premature mortality worldwide, but data
      on its epidemiology in Africa, the world's second most populous continent, are
      limited. METHODS: We systematically reviewed published literature on suicidal
      behaviour in African countries. We searched PubMed, Web of Knowledge, PsycINFO,
      African Index Medicus, Eastern Mediterranean Index Medicus and African Journals
      OnLine and carried out citation searches of key articles. We crudely estimated
      the incidence of suicide and suicide attempts in Africa based on country-specific
      data and compared these with published estimates. We also describe common
      features of suicide and suicide attempts across the studies, including
      information related to age, sex, methods used and risk factors. RESULTS: Regional
      or national suicide incidence data were available for less than one third (16/53)
      of African countries containing approximately 60% of Africa's population; suicide
      attempt data were available for <20% of countries (7/53). Crude estimates suggest
      there are over 34,000 (inter-quartile range 13,141 to 63,757) suicides per year
      in Africa, with an overall incidence rate of 3.2 per 100,000 population. The
      recent Global Burden of Disease (GBD) estimate of 49,558 deaths is somewhat
      higher, but falls within the inter-quartile range of our estimate. Suicide rates
      in men are typically at least three times higher than in women. The most
      frequently used methods of suicide are hanging and pesticide poisoning. Reported
      risk factors are similar for suicide and suicide attempts and include
      interpersonal difficulties, mental and physical health problems, socioeconomic
      problems and drug and alcohol use/abuse. Qualitative studies are needed to
      identify additional culturally relevant risk factors and to understand how risk
      factors may be connected to suicidal behaviour in different socio-cultural
      contexts. CONCLUSIONS: Our estimate is somewhat lower than GBD, but still clearly
      indicates suicidal behaviour is an important public health problem in Africa.
      More regional studies, in both urban and rural areas, are needed to more
      accurately estimate the burden of suicidal behaviour across the continent.
      Qualitative studies are required in addition to quantitative studies.

PMID- 24927747
TI  - Remotely-sensed, nocturnal, dew point correlates with malaria transmission in
      Southern Province, Zambia: a time-series study.
AB  - BACKGROUND: Plasmodium falciparum transmission has decreased significantly in
      Zambia in the last decade. The malaria transmission is influenced by
      environmental variables. Incorporation of environmental variables in models of
      malaria transmission likely improves model fit and predicts probable trends in
      malaria disease. This work is based on the hypothesis that remotely-sensed
      environmental factors, including nocturnal dew point, are associated with malaria
      transmission and sustain foci of transmission during the low transmission season
      in the Southern Province of Zambia. METHODS: Thirty-eight rural health centres in
      Southern Province, Zambia were divided into three zones based on transmission
      patterns. Correlations between weekly malaria cases and remotely-sensed nocturnal
      dew point, nocturnal land surface temperature as well as vegetation indices and
      rainfall were evaluated in time-series analyses from 2012 week 19 to 2013 week
      36. Zonal as well as clinic-based, multivariate, autoregressive, integrated,
      moving average (ARIMAX) models implementing environmental variables were
      developed to model transmission in 2011 week 19 to 2012 week 18 and forecast
      transmission in 2013 week 37 to week 41. RESULTS: During the dry, low
      transmission season significantly higher vegetation indices, nocturnal land
      surface temperature and nocturnal dew point were associated with the areas of
      higher transmission. Environmental variables improved ARIMAX models. Dew point
      and normalized differentiated vegetation index were significant predictors and
      improved all zonal transmission models. In the high-transmission zone, this was
      also seen for land surface temperature. Clinic models were improved by adding dew
      point and land surface temperature as well as normalized differentiated
      vegetation index. The mean average error of prediction for ARIMAX models ranged
      from 0.7 to 33.5%. Forecasts of malaria incidence were valid for three out of
      five rural health centres; however, with poor results at the zonal level.
      CONCLUSIONS: In this study, the fit of ARIMAX models improves when environmental
      variables are included. There is a significant association of remotely-sensed
      nocturnal dew point with malaria transmission. Interestingly, dew point might be
      one of the factors sustaining malaria transmission in areas of general aridity
      during the dry season.

PMID- 24927748
TI  - Doppler ultrasound findings correlate with tissue vascularity and inflammation in
      surgical pathology specimens from patients with small intestinal Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is routinely evaluated using clinical symptoms,
      laboratory variables, and the CD activity index (CDAI). However, clinical
      parameters are often nonspecific and do not precisely reflect the actual activity
      of CD small-intestinal lesions. The purposes of this prospective study were to
      compare color Doppler ultrasound (US) findings with histological findings from
      surgically resected specimens and confirm the hypothesis that color Doppler US
      can distinguish tissue inflammation and fibrosis. METHODS: Among 1764 consecutive
      patients who underwent color Doppler US examinations, 10 patients with CD (12
      small-intestinal CD lesions) who underwent US examinations before elective small
      intestine resection were evaluated in the present study. Areas of thickened
      intestinal walls were evaluated in terms of blood flow using color Doppler US
      imaging. The blood flow was semiquantitatively classified as "hyper-flow" and
      "hypo-flow" according to the Limberg score. Resected lesions were macroscopically
      and histopathologically processed. Inflammatory cell infiltration, fibrosis and
      vascularity were evaluated by myeloperoxidase (granulocytes), CD163
      (macrophages), CD79a (B cells), CD3 (T cells), Masson's trichrome (fibrosis), and
      factor VIII staining (vascular walls). All histopathological images were entered
      into virtual slide equipment and quantified using a quantitative microscopy
      integrated system (TissueMorphTM). RESULTS: There were no significant differences
      in disease features or laboratory findings between "hypo-flow" lesions (n = 4)
      and "hyper-flow" lesions (n = 8). Histopathologically, "hyper-flow" lesions
      showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and
      inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T
      cells, and CD79a B cells (p = 0.043), than did "hypo-flow" lesions. There was no
      apparent association between the blood flow and CDAI. CONCLUSIONS: In this study,
      active CD lesions were macroscopically visible in surgical specimens of patients
      with increased blood flow on preoperative color Doppler US imaging. Additionally,
      these CD lesions exhibited significantly greater vascularity and numbers of
      inflammatory leukocytes microscopically. Color Doppler US may predict tissue
      inflammation and fibrosis in small-intenstinal CD lesions.

PMID- 24927749
TI  - RITA (Reactivating p53 and Inducing Tumor Apoptosis) is efficient against
      TP53abnormal myeloma cells independently of the p53 pathway.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of the p53
      reactivating drugs RITA and nutlin3a in killing myeloma cells. METHODS: A large
      cohort of myeloma cell lines (n = 32) and primary cells (n = 21) was used for
      this study. This cohort contained cell lines with various TP53 statuses and
      primary cells with various incidences of deletion of chromosome 17. Apoptosis was
      evaluated using flow cytometry with Apo2.7 staining of the cell lines or via the
      loss of the myeloma-specific marker CD138 in primary cells. Apoptosis was further
      confirmed by the appearance of a subG1 peak and the activation of caspases 3 and
      9. Activation of the p53 pathway was monitored using immunoblotting via the
      expression of the p53 target genes p21, Noxa, Bax and DR5. The involvement of p53
      was further studied in 4 different p53-silenced cell lines. RESULTS: Both drugs
      induced the apoptosis of myeloma cells. The apoptosis that was induced by RITA
      was not related to the TP53 status of the cell lines or the del17p status of the
      primary samples (p = 0.52 and p = 0.80, respectively), and RITA did not commonly
      increase the expression level of p53 or p53 targets (Noxa, p21, Bax or DR5) in
      sensitive cells. Moreover, silencing of p53 in two TP53(mutated) cell lines
      failed to inhibit apoptosis that was induced by RITA, which confirmed that RITA
      induced apoptosis in myeloma cells was p53 independent. In contrast, apoptosis
      induced by nutlin3a was directly linked to the TP53 status of the cell lines and
      primary samples (p < 0.001 and p = 0.034, respectively) and nutlin3a increased
      the level of p53 and p53 targets in a p53-dependent manner. Finally, we showed
      that a nutlin3a-induced DR5 increase (>= 1.2-fold increase) was a specific and
      sensitive marker (p < 0.001) for a weak incidence of 17p deletion within the
      samples (<= 19%). CONCLUSION: These data show that RITA, in contrast to nutlin3a,
      effectively induced apoptosis in a subset of MM cells independently of p53. The
      findings and could be of interest for patients with a 17p deletion, who are
      resistant to current therapies.

PMID- 24927751
TI  - Differential expression of p42.3 in low- and high-grade gliomas.
AB  - BACKGROUND: Malignant gliomas are the most common form of primary malignant brain
      tumor. It has recently been suggested that genetic changes are involved in the
      progression of malignant gliomas. In previous studies, a novel gene, p42.3, was
      characterized as a tumor-specific gene that encodes a mitosis phase-dependent
      expression protein which is expressed in gastric cancer, but not in matched
      normal tissues. METHODS: In a series of 200 human brain gliomas and 13 normal
      tissues, we performed RT-PCR and mRNA in situ hybridization for analysis of p42.3
      gene expression in gliomas, including astrocytoma (grade 2), oligoastrocytomas
      (grade 2), anaplastic oligoastrocytomas (grade 3), glioblastomas (grade 4) and
      normal tissues. Also, the mRNA expression was detected in gliomas by in situ
      hybridization. After producing polyclonal antibody to p42.3, we further tested
      p42.3 protein expression in astrocytomas and glioblastomas by
      immunohistochemistry and Western blot analysis. RESULTS: Our results demonstrated
      that overexpression of the p42.3 gene is detected in gliomas, but not in normal
      brain tissues. Importantly, p42.3 mRNA expression is correlated with the
      pathological features of gliomas. In addition, p42.3 protein is expressed in both
      the cytoplasm and the nucleus in astrocytomas, whereas this protein appeared in
      the cytoplasm in glioblastomas. CONCLUSIONS: These results indicate that p42.3
      might be involved in carcinogenesis as a potential molecular marker for malignant
      gliomas.

PMID- 24927750
TI  - Documentation of guideline adherence in antenatal records across maternal weight
      categories: a chart review.
AB  - BACKGROUND: Documentation in medical records fulfills key functions, including
      management of care, communication, quality assurance and record keeping. We
      sought to describe: 1) rates of standard prenatal care as documented in medical
      charts, and given the higher risks with excess weight, whether this documentation
      varied among normal weight, overweight and obese women; and 2) adherence to
      obesity guidelines for obese women as documented in the chart. METHODS: We
      conducted a chart review of 300 consecutive charts of women who delivered a live
      singleton at an academic tertiary centre from January to March 2012, computing
      Analysis of Variance and Chi Square tests. RESULTS: The proportion of completed
      fields on the mandatory antenatal forms varied from 100% (maternal age) to 52.7%
      (pre-pregnancy body mass index). Generally, documentation of care was similar
      across all weight categories for maternal and prenatal genetic screening tests,
      ranging from 54.0% (documentation of gonorrhea/chlamydia tests) to 85.0%
      (documentation of anatomy scan). Documentation of education topics varied widely,
      from fetal movement in almost all charts across all weight categories but
      discussion of preterm labour in only 20.6%, 12.7% and 13.4% of normal weight,
      overweight and obese women's charts (p = 0.224). Across all weight categories,
      documentation of discussion of exercise, breastfeeding and pain management
      occurred in less than a fifth of charts. CONCLUSION: Despite a predominance of
      excess weight in our region, as well as increasing perinatal risks with
      increasing maternal weight, weight-related issues and other elements of prenatal
      care were suboptimally documented across all maternal weight categories, despite
      an obesity guideline.

PMID- 24927752
TI  - Pulmonary alveolar proteinosis in children on La Reunion Island: a new inherited
      disorder?
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a
      few small series have been published, with little information about long-term
      progression. The objective of our study was to describe the clinical,
      radiological and pathological features, and the long-term course of PAP in a
      cohort of 34 children from La Reunion Island. METHODS: Data were retrospectively
      collected from medical files. Radiological and pathological elements were
      reviewed by two pediatric radiologists and three pathologists, respectively.
      RESULTS: Thirteen cases were familial and 32/34 (94%) cases were family
      connected. Disease onset occurred in the first six months of life in 82% of the
      patients. Thoracic computed tomography scans showed the typical "crazy-paving"
      pattern in 94% of cases. Respiratory disease was associated with a liver
      disorder, with the detection of liver enlargement at diagnosis in 56% of cases.
      The course of the disease was characterized by frequent progression to chronic
      respiratory insufficiency, accompanied by the appearance of cholesterol
      granulomas and pulmonary fibrosis. Overall prognosis was poor, with a mortality
      of 59% and an overall five-year survival rate from birth of 64%. Whole-lung
      lavages were performed in 21 patients, with no significant effect on survival.
      Liver disease progressed to cirrhosis in 18% of children, with no severe
      complication. CONCLUSIONS: PAP in children from la Reunion Island is
      characterized by an early onset, associated liver involvement, poor prognosis and
      frequent progression to lung fibrosis, despite whole-lung lavages treatment. The
      geographic clustering of patients and the detection of many familial links
      between most of the cases strongly suggest a genetic etiology, with an autosomal
      recessive mode of inheritance.

PMID- 24927753
TI  - A three-dimensional analysis of the morphological evolution and locomotor
      behaviour of the carnivoran hind limb.
AB  - BACKGROUND: The shape of the appendicular bones in mammals usually reflects
      adaptations towards different locomotor abilities. However, other aspects such as
      body size and phylogeny also play an important role in shaping bone design.We
      used 3D landmark-based geometric morphometrics to analyse the shape of the hind
      limb bones (i.e., femur, tibia, and pelvic girdle bones) of living and extinct
      terrestrial carnivorans (Mammalia, Carnivora) to quantitatively investigate the
      influence of body size, phylogeny, and locomotor behaviour in shaping the
      morphology of these bones. We also investigated the main patterns of
      morphological variation within a phylogenetic context. RESULTS: Size and
      phylogeny strongly influence the shape of the hind limb bones. In contrast,
      adaptations towards different modes of locomotion seem to have little influence.
      Principal Components Analysis and the study of phylomorphospaces suggest that the
      main source of variation in bone shape is a gradient of slenderness-robustness.
      CONCLUSION: The shape of the hind limb bones is strongly influenced by body size
      and phylogeny, but not to a similar degree by locomotor behaviour. The slender
      robust "morphological bipolarity" found in bone shape variability is probably
      related to a trade-off between maintaining energetic efficiency and withstanding
      resistance to stresses. The balance involved in this trade-off impedes the
      evolution of high phenotypic variability. In fact, both morphological extremes
      (slender/robust) are adaptive in different selective contexts and lead to a
      convergence in shape among taxa with extremely different ecologies but with
      similar biomechanical demands. Strikingly, this "one-to-many mapping" pattern of
      evolution between morphology and ecology in hind limb bones is in complete
      contrast to the "many-to-one mapping" pattern found in the evolution of
      carnivoran skull shape. The results suggest that there are more constraints in
      the evolution of the shape of the appendicular skeleton than in that of skull
      shape because of the strong biomechanical constraints imposed by terrestrial
      locomotion.

PMID- 24927754
TI  - Effect of seasonal variation on hospital admission due to cardiovascular disease 
      findings from an observational study in a divisional hospital in Bangladesh.
AB  - BACKGROUND: Seasonal variation in the hospital admission due to cardiovascular
      disease (CVDs) has been widely reported. However, very limited data on Bangladesh
      is available regarding this matter. The aim of the current study was to
      investigate the effect of seasonal variation on hospital admission due to CVDs in
      a leading hospital of Bangladesh. METHODS: Over a period of two years (from May
      2010 to April 2012), the number of patients hospitalized due to various CVDs and
      number of death among these hospitalized patients were recorded on a day-to-day
      basis. The data were recorded according to the chief reason of hospital admission
      such as myocardial infarction or MI (acute, old and non-ST elevation), unstable
      angina (UA), exaggeration of stable angina, acute left ventricular failure (LVF),
      cardiomyopathy (ischemic and dilated) or heart failure, syncope and arrhythmia.
      The data were cumulated and analyzed on month-wise and season-wise manner.
      RESULTS: A total of 8371 patients were admitted over the study period (5909 male
      and 2462 female; M/F ratio - 2.4:1). The highest number of patients were admitted
      during winter (n = 2839, 33.9%) and lowest during summer (n = 1648, 19.7%). The
      hospital admission was also significantly higher in winter compared to other
      seasons (p-value versus summer, autumn and spring was 0.018, 0.020 and 0.023
      respectively). Acute MI (n = 2374), Acute LVF (n = 1582) and UA (n = 1277) were
      the top three reasons for hospitalization. Number of death also significantly
      higher in winter compared to other seasons (p-value versus summer, winter and
      spring was 0.044, 0.050 and 0.014 respectively). CONCLUSION: A seasonal variation
      in the hospital admission due to CVDs with a peak in winter was clearly
      demonstrated in the study. These data could be useful to improve causative
      prevention measures, therapeutic management, and educational strategies.

PMID- 24927755
TI  - Non-motor symptoms profile and burden in drug naive versus long-term Parkinson's
      disease patients.
AB  - BACKGROUND: Recent studies have demonstrated that, contrary to common perception
      non-motor symptoms (NMS) occur and may dominate early and untreated stage of
      Parkinson's disease (PD). OBJECTIVE: The aim of this ongoing study was to
      describe the overall NMS profile and burden in drug naive PD patients (DNPD)
      compared to a group of long-term PD patients (LTPD, disease duration >=15 years).
      METHODS: Cross sectional UK data from a multicenter (16 sites) collaboration were
      obtained and specifically NMS dataset from validated scales were analysed in DNPD
      and LTPD patients. The NMS scale (NMSS) was used as the primary outcome variable.
      RESULTS: Out of a current database of 468 PD patients, 57 were DNPD (58% males,
      mean age 64.8 years, median Hoehn and Yahr stage 1) and 25 were LTPD (44%, mean
      age 67.6 years, median Hoehn and Yahr stage 3). DNPD patients had a significantly
      lower (p = 0.001) NMSS score (mean 45.5, range 1-150) compared to the LTPD
      patients (mean 74.0, range 6-155), but 26.3% had severe and 19.3% had very severe
      burden of NMSS using NMSS cutoff scores. In comparison, 20.0% of the LTPD
      patients had severe and 60.0% very severe burden of NMS (p = 0.003). CONCLUSIONS:
      NMS are common in DNPD patients and over 45% may have severe to very severe
      burden of NMS, which is a key determinant of quality of life. In LTPD patients
      not only the burden of "very severe" NMS is significantly higher, but there are
      also differences in the profile of expression of NMS.

PMID- 24927756
TI  - Metabolite and peptide levels in plasma and CSF differentiating healthy controls
      from patients with newly diagnosed Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive, multi-focal
      neurodegenerative disease for which there is no effective disease modifying
      treatment. A critical requirement for designing successful clinical trials is the
      development of robust and reproducible biomarkers identifying PD in preclinical
      stages. OBJECTIVE: To investigate the potential for a cluster of biomarkers
      visualized with multiple analytical platforms to provide a clinically useful
      tool. METHODS: Gas Chromatography-Mass Spectrometry (GC-TOFMS) based metabolomics
      and immunoassay-based protein/peptide analyses on samples from patients with PD
      diagnosed in Northern Sweden. Low molecular weight compounds from both plasma and
      cerebrospinal fluid (CSF) from 20 healthy subjects (controls) and 20 PD patients
      at the time of diagnosis (baseline) were analyzed. RESULTS: In plasma, we found a
      significant increase in several amino acids and a decrease in C16-C18 saturated
      and unsaturated fatty acids in patients as compared to control subjects. We also
      observed an increase in plasma levels of pyroglutamate and 2-oxoisocaproate
      (ketoleucine) that may be indicative of increased metabolic stress in patients.
      In CSF, there was a generally lower level of metabolites in PD as compared to
      controls, with a specific decrease in 3-hydroxyisovaleric acid, tryptophan and
      creatinine. Multivariate analysis and modeling of metabolites indicates that
      while the PD samples can be separated from control samples, the list of detected
      compounds will need to be expanded in order to define a robust predictive model.
      CSF biomarker immunoassays of candidate peptide/protein biomarkers revealed a
      significant decrease in the levels of Abeta-38 and Abeta-42, and an increase in
      soluble APPalpha in CSF of patients. Furthermore, these peptides showed
      significant correlations to each other, and positive correlations to the CSF
      levels of several 5- and 6-carbon sugars. However, combining these metabolites
      and proteins/peptides into a single model did not significantly improve the
      statistical analysis. CONCLUSIONS: Together, this metabolomics study has detected
      significant alterations in plasma and CSF levels of a cluster of amino acids,
      fatty acids and sugars based on clinical diagnosis and levels of known protein
      and peptide biomarkers.

PMID- 24927757
TI  - Ferromagnetic Spin Coupling through the 3,4'-Biphenyl Moiety in Arylamine
      Oligomers-Experimental and Computational Study.
AB  - This report describes the study of a dimer d2+ and a linear trimer t3+ of
      amminium radical cations coupled by 3,4'-biphenyl spin coupling units. The
      synthesis of the parent diamine and triamine and their optical and
      electrochemical properties obtained by UV-visible and cyclic voltammetry are
      presented. The chemical doping of the parent diamine d and triamine t was
      performed quantitatively to obtain samples containing the corresponding dimer d2+
      and trimer t3+ in almost pure high-spin states as evidenced by pulsed EPR
      nutation spectroscopy. The J coupling constants of the corresponding S = 1 and S
      = 3/2 spin states were measured (J/k = 135 K) and compared quantitatively to DFT
      calculations.

PMID- 24927759
TI  - Health diplomacy: a new approach to the Muslim world?
AB  - Three years ago, the Lancet's frontispiece stated "Health is now the most
      important foreign policy issue of our time" and last year, the Director-General
      of WHO, Margaret Chan, in her opening address, to the Executive Board at its
      132nd Session said "health diplomacy works". The nascent field of health
      diplomacy provides a political framework which aims to deliver the dual goals of
      improved health in target populations and enhanced governmental relations between
      collaborating countries. Any government that offered tangible health improvement
      as a component of aid to a nation with whom they wished to develop stronger
      diplomatic links would have an advantage in developing a deeper relationship with
      its citizens.Here we suggest several different mechanisms through which such
      links could be developed or enhanced, including: provision of relevant health
      solutions, applied research, cultural alignment and the development of
      collaborative networks. The Islamic tradition promotes the practice of medicine
      as a service to humanity. Physical and spiritual wellbeing are intimately related
      in popular Muslim consciousness. Thoughtful Health Diplomacy therefore has the
      potential to bridge the perceived divides between Western and predominantly
      Muslim nations. 

PMID- 24927758
TI  - Drug costs in the management of metastatic castration-resistant prostate cancer
      in Canada.
AB  - BACKGROUND: For Canadian men, prostate cancer (PCa) is the most common cancer and
      the 3rd leading cause of cancer mortality. Men dying of PCa do so after failing
      castration. The management of metastatic castration-resistant prostate cancer
      (mCRPC) is complex and the associated drug treatments are increasingly costly.
      The objective of this study was to estimate the cost of drug treatments over the
      mCRPC period, in the context of the latest evidence-based approaches. METHODS:
      Two Markov models with Monte-Carlo microsimulations were developed in order to
      simulate the management of the disease and to estimate the cost of drug
      treatments in mCRPC, as per Quebec's public healthcare system. The models include
      recently approved additional lines of treatment after or before docetaxel (i.e.
      abiraterone and cabazitaxel). Drug exposure and survival were based on clinical
      trial results and clinical practice guidelines found in a literature review. All
      costs were assigned in 2013 Canadian dollars ($). Only direct drug costs were
      estimated. RESULTS: The mean cost of mCRPC drug treatments over an average period
      of 28.1 months was estimated at $48,428 per patient (95% Confidence Interval:
      $47,624 to $49,232). The mean cost increased to $104,071 (95% CI: $102,373 -
      $105,770) per patient when one includes abiraterone initiation prior to docetaxel
      therapy. Over the mCRPC period, luteinizing hormone-releasing hormone agonists
      (LHRHa) prescribed to maintain castrate testosterone levels accounted for 20.4%
      of the total medication cost, whereas denosumab prescribed to decrease bone
      related events accounted for 30.5% of costs. When patients received cabazitaxel
      in sequence after abiraterone and docetaxel, the mCRPC medications cost per
      patient per month increased by 60.2%. The total cost of medications for the
      treatment of each annual Canadian cohort of 4,000 mCRPC patients was estimated at
      $ 193.6 million to $416.3 million. CONCLUSIONS: Our study estimates the direct
      drug costs associated with mCRPC treatments in the Canadian healthcare system.
      Recently identified effective yet not approved therapies will become part of the
      spectrum of mCRPC treatments, and may potentially increase the cost.

PMID- 24927760
TI  - An expert-based job exposure matrix for large scale epidemiologic studies of
      primary hip and knee osteoarthritis: the Lower Body JEM.
AB  - BACKGROUND: When conducting large scale epidemiologic studies, it is a challenge
      to obtain quantitative exposure estimates, which do not rely on self-report where
      estimates may be influenced by symptoms and knowledge of disease status. In this
      study we developed a job exposure matrix (JEM) for use in population studies of
      the work-relatedness of hip and knee osteoarthritis. METHODS: Based on all 2227
      occupational titles in the Danish version of the International Standard
      Classification of Occupations (D-ISCO 88), we constructed 121 job groups
      comprising occupational titles with expected homogeneous exposure patterns in
      addition to a minimally exposed job group, which was not included in the JEM. The
      job groups were allocated the mean value of five experts' ratings of daily
      duration (hours/day) of standing/walking, kneeling/squatting, and whole-body
      vibration as well as total load lifted (kg/day), and frequency of lifting loads
      weighing >=20 kg (times/day). Weighted kappa statistics were used to evaluate
      inter-rater agreement on rankings of the job groups for four of these exposures
      (whole-body vibration could not be evaluated due to few exposed job groups). Two
      external experts checked the face validity of the rankings of the mean values.
      RESULTS: A JEM was constructed and English ISCO codes were provided where
      possible. The experts' ratings showed fair to moderate agreement with respect to
      rankings of the job groups (mean weighted kappa values between 0.36 and 0.49).
      The external experts agreed on 586 of the 605 rankings. CONCLUSION: The Lower
      Body JEM based on experts' ratings was established. Experts agreed on rankings of
      the job groups, and rankings based on mean values were in accordance with the
      opinion of external experts.

PMID- 24927761
TI  - Adjudin protects against cerebral ischemia reperfusion injury by inhibition of
      neuroinflammation and blood-brain barrier disruption.
AB  - Neuroinflammation mediated by activation of microglia and interruption of the
      blood-brain barrier (BBB) is an important factor that contributes to neuron death
      and infarct area diffusion in ischemia reperfusion injury. Finding novel
      molecules to regulate neuroinflammation is of significant clinical value. We have
      previously shown that adjudin, a small molecule compound known to possess
      antispermatogenic function, attenuates microglia activation by suppression of the
      NF-kappaB pathway. In this study we continued to explore whether adjudin could be
      neuroprotective by using the transient middle cerebral artery occlusion (tMCAO)
      model. Adjudin treatment after reperfusion significantly decreased the infarction
      volume and neuroscore compared to the vehicle group. Staining of CD11b showed
      that adjudin markedly inhibited microglial activation in both the cortex and the
      striatum, accompanied by a reduction in the expression and release of cytokines
      TNF-alpha, IL-1beta and IL-6. Concomitantly, adjudin noticeably prevented BBB
      disruption after ischemia and reperfusion, as indicated by the reduction of IgG
      detection in the brain cortex and striatum versus the vehicle group. This finding
      was also corroborated by immunofluorescence staining and immunoblotting of tight
      junction-related proteins ZO-1, JAM-A and Occludin, where the reduction of these
      proteins could be attenuated by adjudin treatment. Moreover, adjudin obviously
      inhibited the elevated MMP-9 activity after stroke. Together these data
      demonstrate that adjudin protects against cerebral ischemia reperfusion injury,
      and we present an effective neuroinflammation modulator with clinical potential. 

PMID- 24927762
TI  - Placental infections with histologically confirmed Plasmodium falciparum are
      associated with adverse birth outcomes in India: a cross-sectional study.
AB  - BACKGROUND: Few studies have assessed placental malaria infections from low
      transmission areas by histopathology to define their impact and underlying
      mechanisms. METHODS: Peripheral smears and rapid diagnostic tests (RDTs),
      placental smears and histological samples, birth weight and gestational age were
      collected from 2,282 deliveries in three hospitals during a one-year (2006-2007)
      continuous cross-sectional survey in Madhya Pradesh. Placental histopathology
      included all 50 cases positive by microscopy or RDT plus 456 randomly selected
      samples of women negative for malaria by microscopy or RDT. Histological
      examination included parasites, inflammatory cells, pigment in fibrin, and
      morphological changes. RESULTS: There were 52 histology-positive cases; 38
      (73.1%) active (acute and chronic) and 14 past infections. Intervillous
      parasitaemia was low (60% had < 1% parasitaemia) and monocytosis mostly mild
      (63%). Compared with uninfected placentas, acute Plasmodium falciparum infections
      were associated with stillbirth (RR 3.8, 95% CI 1.2-12.1), lower maternal
      haemoglobin (mean difference: 1.5 g/dL, 95% CI 0.5-2.5), lower birth weight (mean
      difference 451 g, 95% CI 169-609) and shorter gestation (mean difference 0.8
      weeks, 95% CI 0.2-1.4). Chronic or past infections were not associated with these
      outcomes. Among the 11 peripheral Plasmodium vivax cases, placental parasites
      were absent, but they were associated with increased placental polymorphonuclear
      cells. CONCLUSIONS: Malaria associated stillbirth and low birth weight in women
      with low protective immunity may result, at least in part, from a shortened
      gestation triggered by acute infection, stressing the importance of early malaria
      detection.

PMID- 24927764
TI  - Unit of observation versus unit of analysis.

PMID- 24927763
TI  - Evidence based medicine: a movement in crisis?

PMID- 24927765
TI  - Afghanistan: a healthy future?

PMID- 24927766
TI  - Patients are deceived over benefits and risks of screening, MPs hear.

PMID- 24927767
TI  - Commissioners in Bristol agree to procurement policy changes after legal
      challenge.

PMID- 24927768
TI  - Melioidosis presenting as lymphadenitis: a case report.
AB  - BACKGROUND: Melioidosis is an infection caused by the facultative intracellular
      gram-negative bacterium; Burkholderia pseudomallei. It gives rise to protean
      clinical manifestations and has a varied prognosis. Although it was rare in Sri
      Lanka increasing numbers of cases are being reported with high morbidity and
      mortality. Here we report a case of melioidosis presenting with lymphadenitis
      which was diagnosed early and treated promptly with a good outcome. CASE
      PRESENTATION: A 53-year-old Sinhalese woman with diabetes presented with fever
      and left sided painful inguinal lymphadenitis for one month. She had undergone
      incision and drainage of a thigh abscess three months previously and had been
      treated with a short course of antibiotics. There was no record that abscess
      material was tested microbiologically.She had neutrophil leukocytosis and
      elevated inflammatory markers. Initial pus culture revealed a scanty growth of
      "Pseudomonas sp." and Escherichia coli which were sensitive to ceftazidime and
      resistant to gentamicin.Due to the history of diabetes, recurrent abscess
      formation and the suggestive sensitivity pattern of the bacterial isolates, we
      actively investigated for melioidosis. The bacterial isolate was subsequently
      identified as B. pseudomallei by polymerase chain reaction and antibodies to
      melioidin antigen were found to be raised at a titre of 1:160.The patient was
      treated with high dose intravenous ceftazidime for four weeks followed by
      eradication therapy with cotrimoxazole and doxycycline. As the patient was
      intolerant to cotrimoxazole, the antibiotics were changed to a combination of co
      amoxyclav and doxycycline and continued for 12 weeks. The patient was well after
      6 months without any relapse. CONCLUSIONS: Melioidosis is an emerging infection
      in South Asia. It may present with recurrent abscesses. Therefore it is very
      important to send pus for culture whenever an abscess is drained. However, it
      should be noted that the reporting laboratory may be unfamiliar with this
      bacterium and the isolate may be misidentified as Pseudomonas or even E. coli.
      Melioidosis should be suspected when an isolate with the typical antibiotic
      sensitivity pattern of ceftazidime sensitivity and gentamicin resistance is
      cultured, especially in a patient with diabetes. This will expedite diagnosis and
      prompt treatment leading to an excellent prognosis.

PMID- 24927769
TI  - Prevalence of self-reported early glaucoma eye drop bottle exhaustion and
      associated risk factors: a patient survey.
AB  - BACKGROUND: One barrier to patient adherence with chronic topical glaucoma
      treatment is an inadequate amount of medication available between prescription
      refills. We examined the self-reported prevalence of early exhaustion of glaucoma
      eye drops prior to a scheduled refill, and associated risk factors. METHODS: This
      cross-sectional survey was performed at a University-based clinical practice.
      Glaucoma patients at the University of Washington who were experienced with eye
      drop application and were on a steady regimen of self-administered glaucoma drops
      in both eyes took a survey at the time of clinic examination. The main outcome
      measure was self-reported early eye drop bottle exhaustion. RESULTS: 236 patients
      were eligible and chose to participate. In general, patients included were
      relatively healthy (mean 2.3 comorbid medical conditions). Sixty patients (25.4%)
      reported any problem with early exhaustion of eye drop bottles, and this was
      associated with visual acuity <= 20/70 in the better eye (P = .049). Twelve
      patients (5.1%) reported that they "often" (5-7 times per year), "usually" (8-11
      times per year) or "always" ran out of eye drops prior to a scheduled refill.
      Patients affected by this higher level (>= 5 times yearly) of eye drop bottle
      exhaustion were more likely to have poor visual acuity in their worse eye <= 
      20/70 (P = .015) and had significantly lower worse-eye logMAR (P = .043).
      CONCLUSIONS: Self-reported early glaucoma bottle exhaustion regularly affected 5%
      of patients in our population and 25% reported early exhaustion at least once;
      the main risk factor was poor vision in at least one eye. These results may not
      be generalizable to a broad patient population, or to those inexperienced with
      eye drop self-administration. However, this pilot study compels further
      evaluation and consideration of early eye drop bottle exhaustion in glaucoma
      patients.

PMID- 24927771
TI  - Risk of thyroid dysfunction in patients with solid tumors treated with VEGF
      receptor tyrosine kinase inhibitors: a critical literature review and meta
      analysis.
AB  - We performed a systematic review and meta-analysis of thyroid function
      abnormalities associated with seven vascular endothelial growth factor receptor
      (VEGFR) targeted tyrosine kinase inhibitors (sorafenib, sunitinib, axitinib,
      cediranib, pazopanib, regorafenib and vandetanib). Eligible studies included
      randomized Phase II and III trials of patients with solid tumors on sorafenib OR
      sunitinib OR axitinib OR cediranib OR pazopanib OR regorafenib OR vandetanib;
      describing events of hypothyroidism or hyperthyroidism. Our search strategy
      yielded 195 potentially relevant citations on the seven agents from
      Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After
      exclusion of ineligible studies, a total of 12 clinical trials were considered
      eligible for the meta-analysis, including six sunitinib studies, four cediranib
      studies and two axitinib studies. Patients treated with these agents had a
      significantly increased risk of all-grade hypothyroidism and the relative risk
      (RR) of all-grade hypothyroidism was 3.59 (95% CI = 2.40-5.38, p <= 0.0001).
      Exploratory subgroup analysis showed no effect of tumor types or agent used on
      the RR of hypothyroidism. Our meta-analysis has demonstrated that these three
      agents are associated with a significantly increased risk of all-grade
      hypothyroidism; with no difference - on subgroup analysis - between sunitinib and
      cediranib. Clinicians should be aware of these risks and perform regular thyroid
      function monitoring. 

PMID- 24927770
TI  - MicroRNA response to hypoxic stress in soft tissue sarcoma cells: microRNA
      mediated regulation of HIF3alpha.
AB  - BACKGROUND: Hypoxia is often encountered in solid tumors and known to contribute
      to aggressive tumor behavior, radiation- and chemotherapy resistance resulting in
      a poor prognosis for the cancer patient. MicroRNAs (miRNAs) play a role in the
      regulation of the tumor cell response to hypoxia, however, not much is known
      about the involvement of miRNAs in hypoxic signalling pathways in soft tissue
      sarcomas (STS). METHOD: A panel of twelve STS cell lines was exposed to
      atmospheric oxygen concentrations (normoxia) or 1% oxygen (hypoxia) for up to 48
      h. Hypoxic conditions were verified and miRNA expression profiles were assessed
      by LNATM oligonucleotide microarrays and RT-PCR after 24 h. The expression of
      target genes regulated by hypoxia responsive miRNAs is examined by end-point PCR
      and validated by luciferase reporter constructs. RESULTS: Exposure of STS cell
      lines to hypoxic conditions gave rise to upregulation of Hypoxia Inducible Factor
      (HIF) 1alpha protein levels and increased mRNA expression of HIF1 target genes
      CA9 and VEGFA. Deregulation of miRNA expression after 24 h of hypoxia was
      observed. The most differentially expressed miRNAs (p<0.001) in response to
      hypoxia were miR-185-3p, miR-485-5p, miR-216a-5p (upregulated) and miR-625-5p
      (downregulated). The well-known hypoxia responsive miR-210-3p could not be
      reliably detected by the microarray platform most likely for technical reasons,
      however, its upregulation upon hypoxic stress was apparent by qPCR. Target
      prediction algorithms identified 11 potential binding sites for miR-485-5p and a
      single putative miR-210-3p binding site in the 3'UTR of HIF3alpha, the least
      studied member of the HIF family. We showed that HIF3alpha transcripts,
      expressing a 3'UTR containing the miR-485-5p and miR-210-3p target sites, are
      expressed in all sarcoma cell lines and upregulated upon hypoxia. Additionally,
      luciferase reporter constructs containing the 3'UTR of HIF3alpha were used to
      demonstrate regulation of HIF3alpha by miR-210-3p and miR-485-5p. CONCLUSION:
      Here we provide evidence for the miRNA mediated regulation of HIF3alpha by
      hypoxia responsive miRNAs in STS, which may help to tightly regulate and fine
      tune the hypoxic response. This provides a better insight into the mechanisms
      underlying the hypoxic response in STS and may ultimately yield information on
      novel prognostic and predictive markers or targets for treatment.

PMID- 24927772
TI  - Source and regulation of flux variability in Escherichia coli.
AB  - BACKGROUND: Metabolic responses are essential for the adaptation of
      microorganisms to changing environmental conditions. The repertoire of flux
      responses that the metabolic network can display in different external conditions
      may be quantified applying flux variability analysis to genome-scale metabolic
      reconstructions. RESULTS: A procedure is developed to classify and quantify the
      sources of flux variability. We apply the procedure to the latest Escherichia
      coli metabolic reconstruction, in glucose minimal medium, with an additional
      constraint to account for the mechanism coordinating carbon and nitrogen
      utilization mediated by alpha-ketoglutarate. Flux variability can be decomposed
      into three components: internal, external and growth variability. Unexpectedly,
      growth variability is the only significant component of flux variability in the
      physiological ranges of glucose, oxygen and ammonia uptake rates. To obtain
      substantial increases in metabolic flexibility, E. coli must decrease growth rate
      to suboptimal values. This growth-flexibility trade-off gives a straightforward
      interpretation to recent work showing that most overall cell-to-cell flux
      variability in a population of E. coli can be attained sampling a small number of
      enzymes most likely to constrain cell growth. Importantly, it provides an
      explanation for the global reorganization occurring in metabolic networks during
      adaptations to environmental challenges. The calculations were repeated with a
      pathogenic strain and an old reconstruction of the commensal strain, having less
      than 50% of the reactions of the latest reconstruction, obtaining the same
      general conclusions. CONCLUSIONS: In E. coli growing on glucose, growth
      variability is the only significant component of flux variability for all
      physiological conditions explored. Increasing flux variability requires reducing
      growth to suboptimal values. The growth-flexibility trade-off operates in
      physiological and evolutionary adaptations, and provides an explanation for the
      global reorganization occurring during adaptations to environmental challenges.
      The results obtained do not rely on the knowledge of kinetic and regulatory
      details of the system and are highly robust to incomplete or incorrect knowledge
      of the reaction network.

PMID- 24927774
TI  - Allele-specific expression and eQTL analysis in mouse adipose tissue.
AB  - BACKGROUND: The simplest definition of cis-eQTLs versus trans, refers to genetic
      variants that affect expression in an allele specific manner, with implications
      on underlying mechanism. Yet, due to technical limitations of expression
      microarrays, the vast majority of eQTL studies performed in the last decade used
      a genomic distance based definition as a surrogate for cis, therefore exploring
      local rather than cis-eQTLs. RESULTS: In this study we use RNAseq to explore
      allele specific expression (ASE) in adipose tissue of male and female F1 mice,
      produced from reciprocal crosses of C57BL/6J and DBA/2J strains. Comparison of
      the identified cis-eQTLs, to local-eQTLs, that were obtained from adipose tissue
      expression in two previous population based studies in our laboratory, yields
      poor overlap between the two mapping approaches, while both local-eQTL studies
      show highly concordant results. Specifically, local-eQTL studies show ~60%
      overlap between themselves, while only 15-20% of local-eQTLs are identified as
      cis by ASE, and less than 50% of ASE genes are recovered in local-eQTL studies.
      Utilizing recently published ENCODE data, we also find that ASE genes show
      significant bias for SNPs prevalence in DNase I hypersensitive sites that is ASE
      direction specific. CONCLUSIONS: We suggest a new approach to analysis of allele
      specific expression that is more sensitive and accurate than the commonly used
      fisher or chi-square statistics. Our analysis indicates that technical
      differences between the cis and local-eQTL approaches, such as differences in
      genomic background or sex specificity, account for relatively small fraction of
      the discrepancy. Therefore, we suggest that the differences between two eQTL
      mapping approaches may facilitate sorting of SNP-eQTL interactions into true cis
      and trans, and that a considerable portion of local-eQTL may actually represent
      trans interactions.

PMID- 24927775
TI  - High-throughput, automated quantification of white matter neurons in mild
      malformation of cortical development in epilepsy.
AB  - INTRODUCTION: In epilepsy, the diagnosis of mild Malformation of Cortical
      Development type II (mMCD II) predominantly relies on the histopathological
      assessment of heterotopic neurons in the white matter. The exact diagnostic
      criteria for mMCD II are still ill-defined, mainly because findings from previous
      studies were contradictory due to small sample size, and the use of different
      stains and quantitative systems. Advance in technology leading to the development
      of whole slide imaging with high-throughput, automated quantitative analysis
      (WSA) may overcome these differences, and may provide objective, rapid, and
      reliable quantitation of white matter neurons in epilepsy. This study quantified
      the density of NeuN immunopositive neurons in the white matter of up to 142
      epilepsy and control cases using WSA. Quantitative data from WSA was compared to
      two other systems, semi-automated quantitation, and the widely accepted method of
      stereology, to assess the reliability and quality of results from WSA. RESULTS:
      All quantitative systems showed a higher density of white matter neurons in
      epilepsy cases compared to controls (P = 0.002). We found that, in particular,
      WSA with user-defined region of interest (manual) was superior in terms of larger
      sampled size, ease of use, time consumption, and accuracy in region selection and
      cell recognition compared to other methods. Using results from WSA manual, we
      proposed a threshold value for the classification of mMCD II, where 78% of
      patients now classified with mMCD II were seizure-free at the second post
      operatively follow up. CONCLUSION: This study confirms the potential role of WSA
      in future quantitative diagnostic histology, especially for the histopathological
      diagnosis of mMCD.

PMID- 24927776
TI  - High-sensitive troponin T assay for the diagnosis of acute myocardial infarction:
      an economic evaluation.
AB  - BACKGROUND: Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI)
      has a major adverse impact on prognosis in terms of both morbidity and mortality.
      Since conventional cardiac Troponin assays have a low sensitivity for diagnosing
      AMI in the first hours after myocardial necrosis, high-sensitive assays have been
      developed. The aim of this study was to assess the cost effectiveness of a high
      sensitive Troponin T assay (hsTnT), alone or combined with the heart-type fatty
      acid-binding protein (H-FABP) assay in comparison with the conventional cardiac
      Troponin (cTnT) assay for the diagnosis of AMI in patients presenting to the
      hospital with chest pain. METHODS: We performed a cost-utility analysis (quality
      adjusted life years-QALYs) and a cost effectiveness analysis (life years gained
      LYGs) based on a decision analytic model, using a health care perspective in the
      Dutch context and a life time time-horizon. The robustness of model predictions
      was explored using one-way and probabilistic sensitivity analyses. RESULTS: For a
      life time incremental cost of 30.70 Euros, use of hsTnT over conventional cTnT
      results in gain of 0.006 Life Years and 0.004 QALY. It should be noted here that
      hsTnT is a diagnostic intervention which costs only 4.39 Euros/test more than the
      cTnT test. The ICER generated with the use of hsTnT based diagnostic strategy
      comparing with the use of a cTnT-based strategy, is 4945 Euros per LYG and 7370
      Euros per QALY. The hsTnT strategy has the highest probability of being cost
      effective at thresholds between 8000 and 20000 Euros per QALY. The combination of
      hsTnT and h-FABP strategy's probability of being cost effective remains lower
      than hsTnT at all willingness to pay thresholds. CONCLUSION: Our analysis
      suggests that hsTnT assay is a very cost effective diagnostic tool relative to
      conventional TnT assay. Combination of hsTnT and H-FABP does not offer any
      additional economic and health benefit over hsTnT test alone.

PMID- 24927777
TI  - Evidence for the use of glomerulomegaly as a surrogate marker of glomerular
      damage and for alpha-linolenic acid-rich oils in the treatment of early obesity
      related glomerulopathy in a diet-induced rodent model of obesity.
AB  - Obesity-related glomerulopathy (ORG) is a unique and emerging condition that can
      lead to renal failure. Early detection, aided by an earlier diagnostic marker,
      would improve patient outcomes; this could be facilitated by an accurate model.
      Such a model would be useful to examine interventions like dietary fatty acids,
      which are known to influence renal diseases in later stages. In this study, obese
      prone rats were provided high-fat (55% of energy) diets for 12 weeks to generate
      a model of diet-induced obesity. The rats were subsequently provided dietary oils
      with various levels of alpha-linolenic acid (ALA) and linoleic acid (LA) for 8
      weeks, as follows: (g ALA:LA per 100 g oil): canola/flax (20:18), canola (8:18),
      soy (9:53), high-oleic canola/canola (5:16), high-oleic canola (2:15), lard/soy
      (1:8), and safflower (0.2:73). The model developed obesity, glomerulomegaly,
      proteinuria, and scarce glomerular damage with an indolent course. Morphometry
      and histology revealed glomerulomegaly as the first renal structural alteration.
      The utility of this marker as a predictor for the presence of ORG and renal
      injury was evidenced by its correlation to visceral adiposity (p < 0.0001, r =
      0.44), proteinuria (p < 0.0001, rho = 0.55), change in proteinuria (p = 0.0092,
      rho = 0.42), and glomerular damage (p < 0.0001, rho = 0.48). Renal triglyceride
      ALA:LA was strongly correlated with dietary ALA:LA (p < 0.0005, rho = 0.96), and
      inversely associated with mean glomerular volume (p = 0.02, rho = -0.82). The
      diet-induced obese model accurately represents early ORG, and implicates
      glomerulomegaly as an early surrogate diagnostic marker. Early intervention with
      ALA-rich dietary oils slowed glomerular enlargement; these findings warrant
      further clinical investigation to promote optimal patient outcomes. 

PMID- 24927773
TI  - Molecular aspects of development and regulation of endometriosis.
AB  - Endometriosis is a common and painful condition affecting women of reproductive
      age. While the underlying pathophysiology is still largely unknown, much
      advancement has been made in understanding the progression of the disease. In
      recent years, a great deal of research has focused on non-invasive diagnostic
      tools, such as biomarkers, as well as identification of potential therapeutic
      targets. In this article, we will review the etiology and cellular mechanisms
      associated with endometriosis as well as the current diagnostic tools and
      therapies. We will then discuss the more recent genomic and proteomic studies and
      how these data may guide development of novel diagnostics and therapeutics. The
      current diagnostic tools are invasive and current therapies primarily treat the
      symptoms of endometriosis. Optimally, the advancement of "-omic" data will
      facilitate the development of non-invasive diagnostic biomarkers as well as
      therapeutics that target the pathophysiology of the disease and halt, or even
      reverse, progression. However, the amount of data generated by these types of
      studies is vast and bioinformatics analysis, such as we present here, will be
      critical to identification of appropriate targets for further study. 

PMID- 24927778
TI  - Description of gas-phase ion/neutral interactions in differential ion mobility
      spectrometry: CV prediction using calibration runs.
AB  - Differential ion mobility spectrometry (DMS) coupled to mass spectrometry is
      increasingly used in both quantitative analyses of biological samples and as a
      means of removing background interferences for enhanced selectivity and improved
      quality of mass spectra. However, DMS separation efficiency using dry inert gases
      often lacks the required selectivity to achieve baseline separation. Polar gas
      phase modifiers such as alcohols are therefore frequently employed to improve
      selectivity via clustering/declustering processes. The choice of an optimal
      modifier currently relies on trial and error experiments, making method
      development a tedious activity. It was the goal of this study to establish a
      means of CV prediction for compounds using a homologous series of alcohols as gas
      phase modifiers. This prediction was based on linear regression of compensation
      voltages of two calibration runs for the alcohols with the lowest and the highest
      molecular weights and readily available descriptors such as proton affinity and
      gas phase acidity of the modifier molecules. All experiments were performed on a
      commercial quadrupole linear ion trap mass spectrometer equipped with a DMS
      device between electrospray ionization source and entrance quadrupole lens. We
      evaluated our approach using a homologous series of 4-alkylbenzoic acids and a
      selection of 23 small molecules of high chemical diversity. Predicted CV values
      typically deviated from the experimentally determined values by less than 0.5 V.
      Several test compounds changed their ion mobility behavior for the investigated
      gas phase modifiers (e.g., from type B to type A) and thus could thus not be
      evaluated. 

PMID- 24927779
TI  - [Management and prevention of complications in open urethral surgery. End-to-end
      anastomosis and buccal mucosa urethroplasty].
AB  - Open operative procedures for urethral reconstruction (i.e. stricture resection
      with primary end-to-end anastomosis and buccal mucosa urethroplasty) are
      established and proven techniques with a low complication profile and high
      success rates. The aim of this operative technique is removal of the urethral
      obstruction to avoid far-reaching complications for the whole urinary tract.
      Despite excellent long-term results, complications are not completely avoidable
      in both techniques. A successful complication management requires the complete
      spectrum of reconstructive techniques in addition to appropriate operative
      expertise in order to be able to achieve the optimal result even in cases of
      complications. Simultaneously the recognition of potential risks contributes to a
      further reduction of early and delayed complications both in the approach to the
      operative intervention as well as intraoperatively. 

PMID- 24927780
TI  - Pregnancy outcomes in older women.

PMID- 24927781
TI  - Message from the Editor-in-Chief.

PMID- 24927782
TI  - A comparison of maternal and neonatal outcomes of pregnancy with mental
      disorders: results of an analysis using propensity score-based weighting.
AB  - PURPOSE: To assess and compare maternal and neonatal outcomes of pregnancy with
      or without mental disorders. METHODS: We performed a retrospective cohort study
      of births at our institution from January 2009 to December 2011, which included
      all live singleton births during these 3 years. Women emergently transferred to
      our institution in the middle of their pregnancies were excluded. Associations
      between mental disorders and perinatal outcomes were estimated using statistical
      analysis, and multivariable analysis was performed using propensity score-based
      weighting. RESULTS: A total of 1,166 women were included, 152 (13.0 %) of whom
      had mental disorders. Comparison of maternal characteristics showed that women
      with mental disorders were significantly more likely to be multiparous, smokers,
      recipients of public assistance, unmarried, and to have inadequate perinatal
      care. Comparison of perinatal outcomes showed that preterm births (PTB) before 37
      weeks were significantly increased in women with mental disorders (10.5 vs. 6.0
      %, P = 0.037). There were no significant differences in low birth weight (LBW),
      pregnancy-induced hypertension, and gestational diabetes mellitus. Multivariable
      analysis using propensity score weighting showed that after adjusting for other
      factors, women with mental disorders were more likely than women without mental
      disorders to have PTB before 34 weeks [adjusted odds ratio (OR) 4.79, 95 %
      confidence interval (CI) 1.49-15.4; P = 0.009], PTB before 37 weeks (adjusted OR
      2.46, 95 % CI 1.62-3.69; P < 0.001), or LBW (adjusted OR 1.83; 95 % CI 1.32-2.55;
      P < 0.001). CONCLUSION: Maternal mental disorders were associated with adverse
      birth outcomes and socioeconomic disadvantage.

PMID- 24927783
TI  - Impact of Qigong on quality of life, pain and depressive symptoms in older adults
      admitted to an intermediate care rehabilitation unit: a randomized controlled
      trial.
AB  - BACKGROUND AND AIMS: Qigong has been used as a complementary therapy to improve
      different health-related problems. This study aims to test the effects of Qigong
      on quality of life, pain and depressive symptoms in older hospitalized patients.
      METHODS: In this randomized controlled single blind study, we randomized 58 >=50
      years adults admitted to a post-acute intermediate care rehabilitation facility,
      to receive a 90 min, bi-weekly, 4-week structured Qigong intervention plus usual
      care and rehabilitation (N = 29) or usual care and rehabilitation alone (N = 29).
      Outcomes included quality of life (0-100 points visual analogical scale), pain (0
      10 points scale), and depressive symptoms (5-item modified Yesavage Geriatric
      Depression Scale). We also evaluated participants' compliance and safety.
      RESULTS: Of the enrolled 58 participants (mean age +/- SD = 74.3 +/- 8.2 years,
      88 % women) we dropped-out four in the control group. No statistically
      significant differences in baseline characteristics were shown between groups,
      including age, gender, marital status, education, comorbidity and functional
      status, main diagnostic at admission and number of rehabilitation sessions. In an
      intention-to-treat analysis (repeated measures ANOVA) the intervention group
      experienced a significant improvement in quality of life (mean increase of 19
      points vs 2.6 points for controls, p = 0.002). Pain and depressive symptoms
      improved in both groups. Adherence was good (79 % of participants completed the
      whole program). No adverse events were reported. CONCLUSIONS: According to our
      results, a structured Qigong intervention, together with usual care, might
      contribute to improve quality of life of patients admitted to a post-acute
      intermediate care rehabilitation unit, compared to usual care.

PMID- 24927784
TI  - Economic evaluation of surgical insertion of ventilation tubes for the management
      of persistent bilateral otitis media with effusion in children.
AB  - BACKGROUND: The surgical insertion of Ventilation Tubes (VTs) for the management
      of persistent bilateral Otitis Media with Effusion (OME) in children remains a
      contentious issue due to the varying opinions regarding the risks and benefits of
      this procedure. The aim of this study was to evaluate the economic impact of VTs
      insertion for the management of persistent bilateral OME in children, providing
      an additional perspective on the management of one of the commonest medical
      conditions of childhood. METHODS: A decision-tree model was constructed to assess
      the cost-effectiveness of VTs strategy compared with the Hearing Aids (HAs) alone
      and HAs plus VTs strategies. The model used data from published sources, and
      assumed a 2-year time horizon and UK NHS perspective for costs. Outcomes were
      computed as Quality-Adjusted Life-Years (QALYs) by attaching a utility value to
      the total potential gains in Hearing Level in decibels (dBHL) over 12 and 24
      months. Modelling uncertainty in the specification of decision-tree probabilities
      and QALYs was performed through Monte Carlo simulation. Expected Value of Perfect
      Information (EVPI) and partial EVPI (EVPPI) analyses were conducted to estimate
      the potential value of future research and uncertainty associated with the key
      parameters. RESULTS: The VTs strategy was more effective and less costly when
      compared with the HAs plus VTs strategy, while the incremental cost-effectiveness
      ratio for the VTs strategy compared with the HAs strategy was L 5,086 per QALY
      gained. At the willingness-to-pay threshold of L 20,000 per QALY, the probability
      that the VTs strategy is likely to be more cost-effective was 0.58. The EVPI
      value at population level of around L 9.5 million at the willingness-to-pay
      threshold of L 20,000 indicated that future research in this area is potentially
      worthwhile, while the EVPPI analysis indicated considerable uncertainty
      surrounding the parameters used for computing the QALYs for which more precise
      estimates would be most valuable. CONCLUSIONS: The VTs strategy is a cost
      effective option when compared with the HAs alone and HAs plus VTs strategies,
      but the need for additional information from future study is evident to inform
      this surgical treatment choice. Future studies of surgical and non-surgical
      treatment of OME in childhood should evaluate the economic impact of pertinent
      interventions to provide greater context.

PMID- 24927786
TI  - Maternal perceptions of social context and adherence to maternal and child health
      (MCH) clinic recommendations among marginalized Bedouin mothers.
AB  - National maternal and child health (MCH) care systems often deliver universal
      health care recommendations that do not take into consideration the social
      context of infant care (IC) for marginalized groups. We examined associations
      between maternal perceptions of social context (MPSC) and adherence by minority
      Bedouin mothers in Israel to three commonly recommended IC practices. We
      conducted personal interviews with 464 mothers visiting 14 MCH clinics using a
      structured questionnaire based on findings from a previous focus-group study, and
      guided by constructs of the Health Beliefs Model. Items were tested for validity
      and reliability. We used multivariate analysis to identify MPSC constructs
      associated with adherence to MCH clinic recommendations (timely postnatal first
      visit, sustaining breastfeeding, and use of infant car seat). Social context,
      when perceived as a barrier to IC, was negatively associated with adherence to
      timely first postnatal MCH clinic visit (odds ratio, 95 %, confidence intervals
      (OR 1.45, 95 % CI 1.24, 1.70) and use of infant car seat (OR 1.43, 95 % CI 1.21,
      1.69). However, social context was positively associated with sustained
      breastfeeding (OR 0.54, 95 % CI 0.37, 0.79). Perceptions of the severity of
      infant health problems, and family financial and relationship problems had less
      significant associations with adherence to MCH clinic recommendations. Adherence
      by marginalized mothers to MCH clinic recommendations is related to their
      perceptions of social context. When there are higher financial and other living
      conditions barriers mothers tend toward lower adherence to these recommendations.
      MCH policy makers and service providers must consider MPSC in planning and
      delivery of MCH recommendations.

PMID- 24927785
TI  - No association between identified multiple sclerosis non-MHC risk loci and
      neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) and multiple sclerosis (MS) are both autoimmune
      inflammatory and demyelinating disorders of the central nervous system. Recently,
      more than 50 MS-susceptibility single-nucleotide polymorphisms (SNPs) have been
      detected outside the major histocompatibility complex (MHC) region. In this
      study, we aimed to evaluate the association of these identified non-MHC MS risk
      loci with Chinese patients with NMO. Thirty-five non-MHC SNPs were selected and
      genotyped by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) in 110 NMO patients and 332 controls from
      southeastern China. Among the 35 SNPs, only one, rs1800693 in the TNFRSF1A locus,
      was nominally associated with NMO (P = 0.045, OR = 1.550, 95% CI = 1.007-2.384).
      However, none of the 35 SNPs was associated with NMO after Bonferroni correction.
      Our results showed no association between these identified non-MHC MS risk loci
      and NMO, suggesting there are genetic differences in the etiology of NMO and MS.

PMID- 24927787
TI  - Utilisation of health services and geography: deconstructing regional differences
      in barriers to facility-based delivery in Nepal.
AB  - While established that geographical inaccessibility is a key barrier to the
      utilisation of health services, it remains unknown whether disparities are driven
      only by limited access to these services, or are also attributable to health
      behaviour. Significant disparities exist in health outcomes and the coverage of
      many critical health services between the mountains region of Nepal and the rest
      of the country, yet the principal factors driving these regional disparities are
      not well understood. Using national representative data from the 2011 Nepal
      Demographic and Health Survey, we examine the extent to which observable factors
      explain the overall differences in the utilisation of maternal health services.
      We apply nonlinear Blinder-Oaxaca-type decomposition methods to quantify the
      effect that differences in measurable characteristics have on the regional
      coverage gap in facility-based delivery. The mean coverage of facility-based
      deliveries was 18.6 and 36.3 % in the mountains region and the rest of Nepal,
      respectively. Between 54.8 and 74.1 % of the regional coverage gap was explained
      by differences in observed characteristics. Factors influencing health behaviours
      (proxied by mothers' education, TV viewership and tobacco use, and household
      wealth) and subjective distance to the health facility were the major factors,
      contributing between 52.9 and 62.5 % of the disparity. Mothers' birth history was
      also noteworthy. Policies simultaneously addressing access and health behaviours
      appear necessary to achieve greater coverage and better health outcomes for women
      and children in isolated areas.

PMID- 24927788
TI  - Tongxinluo attenuates neuronal loss and enhances neurogenesis and angiogenesis in
      the ipsilateral thalamus and improves neurological outcome after focal cortical
      infarction in hypertensive rats.
AB  - PURPOSE: Tongxinluo, a well-known traditional Chinese medicine complex, has been
      widely used for the treatment of cerebrovascular diseases in China. The present
      study was to explore whether treatment with tongxinluo could improve neurological
      function and alleviate secondary damage in the ipsilateral thalamus after focal
      cortical infarction in hypertensive rats. METHODS: Tongxinluo was given through
      oral gavage starting 24 h after distal middle cerebral artery occlusion (MCAO).
      Neurological function was assessed and then rats were sacrificed 7 and 14 days
      after MCAO. Brains were harvested for examining infarction volume, Nissl staining
      and immunofluorescence analysis. RESULTS: Compared with vehicle treatment,
      tongxinluo remarkably improved neurological function without reducing infarction
      volume, attenuated neuronal loss and astrocyte activation in the ipsilateral
      thalamus 7 and 14 days after MCAO (all p < 0.05). Also, tongxinluo markedly
      increased the number of BrdU+/nestin+ and BrdU+/NeuN+ cells 14 days after MCAO.
      Moreover, vascular density, the number of BrdU+ vascular endothelial cells, and
      vascular perimeter in the ipsilateral thalamus were markedly increased in the
      tongxinluo group relative to that of the vehicle group (all p < 0.05).
      CONCLUSION: Administration of tongxinluo 24 h after cortical infarction may
      promote neurogenesis and angiogenesis in the ipsilateral thalamus and improves
      neurological function after cortical infarction in rats.

PMID- 24927789
TI  - In vitro glucuronidation kinetics of deoxynivalenol by human and animal
      microsomes and recombinant human UGT enzymes.
AB  - The mycotoxin deoxynivalenol (DON), formed by Fusarium species, is one of the
      most abundant mycotoxins contaminating food and feed worldwide. Upon ingestion,
      the majority of the toxin is excreted by humans and animal species as glucuronide
      conjugate. First in vitro data indicated that DON phase II metabolism is strongly
      species dependent. However, kinetic data on the in vitro metabolism as well as
      investigations on the specific enzymes responsible for DON glucuronidation in
      human are lacking. In the present study, the DON metabolism was investigated
      using human microsomal fractions and uridine-diphosphoglucuronyltransferases
      (UGTs) as well as liver microsomes from five animal species. Only two of the
      twelve tested human recombinant UGTs led to the formation of DON glucuronides
      with a different regiospecificity. UGT2B4 predominantly catalyzed the formation
      of DON-15-O-glucuronide (DON-15GlcA), while for UGT2B7 the DON-3-O-glucuronide
      (DON-3GlcA) metabolite prevailed. For human UGTs, liver, and intestinal
      microsomes, the glucuronidation activities were low. The estimated apparent
      intrinsic clearance (Clapp,int) for all human UGT as well as tissue homogenates
      was <1 mL/min mg protein. For the animal liver microsomes, moderate Clapp,int
      between 1.5 and 10 mL/min mg protein were calculated for carp, trout, and porcine
      liver. An elevated glucuronidation activity was detected for rat and bovine liver
      microsomes leading to Clapp,int between 20 and 80 mL/min mg protein. The obtained
      in vitro data points out that none of the animal models is suitable for
      estimating the human DON metabolism with respect to the metabolite pattern and
      formation rate.

PMID- 24927790
TI  - The use of equivalent radiation dose in the evaluation of late effects after
      childhood cancer treatment.
AB  - PURPOSE: In epidemiologic research radiation-associated late effects after
      childhood cancer are usually analyzed without considering fraction dose.
      According to radiobiological principles, fraction dose is an important
      determinant of late effects. We aim to provide the rationale for using equivalent
      dose in 2-Gy fractions (EQD2(alpha/beta)) as the measure of choice rather than
      total physical dose as prescribed according to the clinical protocol. METHODS:
      Between 1966 and 1996, 597 (43.8%) children in our cohort of 1,362 5-year
      childhood cancer survivors (CCS) received radiotherapy before the age of 18 years
      as part of their primary cancer treatment. Detailed information from individual
      patients' charts was collected and physical doses were converted into the
      EQD2(alpha/beta), which includes total dose, fraction dose, and the tissue
      specific alpha/beta ratio. The use of EQD2(alpha/beta) is illustrated in examples
      studies describing different analyses using EQD2(alpha/beta) and physical dose.
      RESULTS: Radiotherapy information was obtained for 510 (85.4%) CCS. Multivariable
      analyses rendered different risk estimates for total body irradiation in
      EQD2(alpha/beta)-based vs. physical-dose-based models. For other radiotherapy
      regimens, risk estimates were similar. CONCLUSIONS: Using the total physical dose
      is not adequate for advanced analyses of radiation-associated late effects in
      CCS. Therefore, it is advised that for future studies the EQD2(alpha/beta) is
      used, because the EQD2(alpha/beta) incorporates the fraction dose, and the tissue
      specific alpha/beta ratio. Furthermore, it enables comparisons across
      fractionation regimens and allows for summing doses delivered by various
      contemporary and future radiation modalities. IMPLICATIONS FOR CANCER SURVIVORS:
      Risk estimates of radiation-associated side effects expressed in EQD2(alpha/beta)
      provide more precise, clinically relevant information for cancer survivor
      screening guidelines.

PMID- 24927791
TI  - The Rodin-Ohno hypothesis that two enzyme superfamilies descended from one
      ancestral gene: an unlikely scenario for the origins of translation that will not
      be dismissed.
AB  - BACKGROUND: Because amino acid activation is rate-limiting for uncatalyzed
      protein synthesis, it is a key puzzle in understanding the origin of the genetic
      code. Two unrelated classes (I and II) of contemporary aminoacyl-tRNA synthetases
      (aaRS) now translate the code. Observing that codons for the most highly
      conserved, Class I catalytic peptides, when read in the reverse direction, are
      very nearly anticodons for Class II defining catalytic peptides, Rodin and Ohno
      proposed that the two superfamilies descended from opposite strands of the same
      ancestral gene. This unusual hypothesis languished for a decade, perhaps because
      it appeared to be unfalsifiable. RESULTS: The proposed sense/antisense alignment
      makes important predictions. Fragments that align in antiparallel orientations,
      and contain the respective active sites, should catalyze the same two reactions
      catalyzed by contemporary synthetases. Recent experiments confirmed that
      prediction. Invariant cores from both classes, called Urzymes after Ur =
      primitive, authentic, plus enzyme and representing ~20% of the contemporary
      structures, can be expressed and exhibit high, proportionate rate accelerations
      for both amino-acid activation and tRNA acylation. A major fraction (60%) of the
      catalytic rate acceleration by contemporary synthetases resides in segments that
      align sense/antisense. Bioinformatic evidence for sense/antisense ancestry
      extends to codons specifying the invariant secondary and tertiary structures
      outside the active sites of the two synthetase classes. Peptides from a designed,
      46-residue gene constrained by Rosetta to encode Class I and II ATP binding sites
      with fully complementary sequences both accelerate amino acid activation by ATP
      ~400 fold. CONCLUSIONS: Biochemical and bioinformatic results substantially
      enhance the posterior probability that ancestors of the two synthetase classes
      arose from opposite strands of the same ancestral gene. The remarkable
      acceleration by short peptides of the rate-limiting step in uncatalyzed protein
      synthesis, together with the synergy of synthetase Urzymes and their cognate
      tRNAs, introduce a new paradigm for the origin of protein catalysts, emphasize
      the potential relevance of an operational RNA code embedded in the tRNA acceptor
      stems, and challenge the RNA-World hypothesis.

PMID- 24927792
TI  - Ectopic ACTH-secreting pituitary adenomas within the sphenoid sinus.
AB  - Ectopic pituitary adenomas are defined by the presence of adenomatous pituitary
      tissue outside the sella and distinctly separate from the pituitary gland.
      Ectopic ACTH-secreting pituitary adenomas (EAPAs) are a rare cause of Cushing's
      syndrome. Detecting these radiologically can prove difficult, in part, due to
      their typically small size and unpredictable anatomical location. In ACTH
      dependent Cushing's syndrome, if, despite comprehensive testing, the source of
      excess ACTH remains occult (including negative work up for ectopic ACTH syndrome)
      thought should be given to the possibility of the patient harboring an EAPA. In
      most cases, ectopic ACTH pituitary adenomas within the sphenoid sinus will
      manifest with symptoms of hormonal excess, have an obvious sphenoid sinus mass on
      pre-operative imaging and will demonstrate resolution of hypercortisolism after
      surgical excision if located and removed. Twenty cases of EAPAs have been
      reported in the literature to date. This paper will review the current literature
      on all previously reported EAPAs within the sphenoid sinus in addition to the
      current case. 

PMID- 24927793
TI  - Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their
      BRAF V600E mutation status.
AB  - Promoter hypermethylation of multiple genes have been identified to play a role
      in thyroid cancers and most prominent among them is TSHR gene promoter
      hypermethylation in particular showing a close association with BRAF gene-altered
      status. Thus, the aim of this study was to analyze the TSHR gene promoter
      hypermethylation in a series of thyroid tumor tissues in the backdrop of their
      BRAF gene mutational status. Methylation-specific PCR (MS-PCR) was used for
      detection of promoter methylation while BRAF gene mutational status was analyzed
      by PCR followed by DNA sequencing in the same series of 60 thyroid tumor tissues.
      The promoter region of TSHR gene was found to be methylated in 25 % (15 of 60) of
      the thyroid cancer patients. Patients having elevated TSH levels showed strong
      association with methylation (OR = 4.0, P = 0.02). BRAF V600E mutation was found
      in 25 % (15 of 60) patients and among them TSHR promoter was methylated in 73.3 %
      (11 of 15) patients and only 26.7 % (4 of 15) patients with mutated BRAF showed
      the absence of TSHR promoter methylation. We found a significant association
      between the presence of methylation in TSHR with the BRAF V600E mutation-positive
      cases (P < 0.05). In conclusion, our study showed a high implication of TSHR gene
      methylation and its significant association with BRAF V600E mutation in thyroid
      tumors, depicting a positive connection between TSHR pathway and MAP Kinase
      pathway.

PMID- 24927795
TI  - Prediction of open urinary tract in laparoscopic partial nephrectomy by virtual
      resection plane visualization.
AB  - BACKGROUND: The purpose of this study is presenting a method to predict the
      presence of an open urinary tract and the position of the opening in laparoscopic
      partial nephrectomy from three dimensional (3D) computed tomography (CT) images
      by using novel image segmentation and visualization techniques. METHODS: From CT
      images of patients who underwent laparoscopic partial nephrectomy, 3D regions of
      the kidney, urinary tract, and tumor were segmented. For each patient, multiple
      virtual resection planes of the kidney with different surgical margins (1 mm to 5
      mm, every 1 mm) were generated and the presence of an open urinary tract and the
      position of the opening were predicted from the images. RESULTS: We compared the
      predictions with actual operations in 5 cases by using recorded video of the
      operations and operative notes. In terms of the presence of an open urinary
      tract, agreement of the predictions and the intraoperative results was obtained
      in all patients. The expected positions of the openings were close to those in
      the actual operations. CONCLUSIONS: We have developed a method to virtually
      visualize the resection plane of laparoscopic partial nephrectomy. Image
      segmentation methods used in this study were precise and effective. The
      comparison indicated that our method accurately predicted the presence of an open
      urinary tract and the position of the opening and provided useful preoperative
      information.

PMID- 24927794
TI  - The association between diabetes and depression: a very disabling condition.
AB  - Rates of depression are significantly increased in diabetic patients, and even
      more in the elderly. About 20-30% of patients with diabetes suffer from
      clinically relevant depressive disorders, 10% of which being affected by the
      major depression disorder. Moreover, people with depression seem to be more prone
      to develop an associated diabetes mellitus, and depression can worsen glycemic
      control in diabetes, with higher risk to develop complications and adverse
      outcomes, whereas improving depressive symptoms is generally associated with a
      better glycemic control. Thus, the coexistence of depression and diabetes has a
      negative impact on both lifestyle and quality of life, with a reduction of
      physical activity and an increase in the request for medical care and
      prescriptions, possibly increasing the healthcare costs and the susceptibility to
      further diseases. These negative aspects are particularly evident in the elderly,
      with further decrease in the mobility, worsening of disability, frailty,
      geriatric syndromes and increased mortality. Healthcare providers should be aware
      of the possible coexistence of depression and diabetes and of the related
      consequences, to better manage the patients affected by these two pathological
      conditions.

PMID- 24927796
TI  - Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 by
      macrophages and increases the resistance of mice against infections.
AB  - BACKGROUND: Palmitoylethanolamide (PEA), an endogenous lipid and a congener of
      anandamide, possesses a wide range of effects related to metabolic and cellular
      homeostasis including anti-inflammatory and neuroprotective properties. METHODS:
      In vitro, we studied the ability of macrophages to phagocytose Escherichia coli
      K1 after stimulation with increasing doses of PEA. In vivo, wild-type mice were
      treated with PEA intraperitoneally 12 hours and 30 minutes before infection.
      Meningoencephalitis or sepsis was induced by intracerebral or intraperitoneal
      infection with E. coli K1. RESULTS: Stimulation of macrophages with PEA for 30
      minutes increased the phagocytosis of E. coli K1 without inducing the release of
      TNFalpha or CXCL1. Intracellular killing of E. coli K1 was higher in PEA
      stimulated than in unstimulated peritoneal macrophages and microglial cells. Pre
      treatment with PEA significantly increased survival of mice challenged
      intracerebrally or intraperitoneally with E. coli K1. This effect was associated
      with a decreased production of CXCL1, IL-1beta and IL-6 in homogenates of spleen
      and cerebellum in mice treated with PEA. CONCLUSIONS: Our observations suggest
      that these protective effects of PEA in mice can increase the resistance to
      bacterial infections without the hazard of collateral damage by excessive
      stimulation of phagocytes.

PMID- 24927797
TI  - The combination of FDG PET and dynamic contrast-enhanced MRI improves the
      prediction of disease-free survival in patients with advanced breast cancer after
      the first cycle of neoadjuvant chemotherapy.
AB  - PURPOSE: The aim of this study was to investigate the potential of FDG PET/CT and
      MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy
      (NAC) and surgery in patients with advanced breast cancer. METHODS: The analysis
      included 54 women with advanced breast cancer. All patients received three cycles
      of NAC, underwent curative surgery, and then received three cycles of additional
      chemotherapy. Before and after the first cycle of NAC, all patients underwent
      sequential PET/CT and MRI. All patients were analysed using a diverse range of
      parameters. including maximal standardized uptake value (SUV), percent change in
      SUV (DeltaSUV), initial slope of the enhancement curve (MRslope), apparent
      diffusion coefficient (ADC), tumour size, change in MRslope (DeltaMRslope),
      change in ADC (DeltaADC), change in tumour size (Deltasize) and other
      clinicopathological parameters]. The relationships between covariates and DFS
      after surgery were analysed using the Kaplan-Meier method and the multivariate
      Cox proportional hazards model. Time-dependent receiver operating characteristic
      curves were used to determine the optimal cut-off values of imaging parameters
      for DFS. RESULTS: Of the 54 patients, 13 (24 %) experienced recurrence at a
      median follow-up of 38 months (range 25 - 45 months). Univariate and multivariate
      analyses showed that a lesser decline in SUV, a lesser decline in MRslope, a
      lesser increase in ADC, and ER negativity were significantly associated with a
      poorer DFS (P = 0.0006, DeltaSUV threshold -41 %; P = 0.0016, DeltaMRslope
      threshold -6 %; P = 0.011, DeltaADC threshold 11 %; and P = 0.0086, ER status,
      respectively). Patients with a combination of DeltaSUV >-41 % and DeltaMRslope >
      6 % showed a significantly higher recurrence rate (77.8 %) than the remaining of
      patients (13.3 %, P < 0.0001). CONCLUSION: Functional parameters of both FDG PET
      and MRI after the first cycle of NAC are useful for predicting DFS in patients
      with advanced breast cancer. This approach could lead to an improvement in
      patient care because ineffective NAC agents could be avoided and more aggressive
      therapy could be used in high-risk patients.

PMID- 24927799
TI  - A case of recurrent intestinal ganglioneuromatous polyposis accompanied with
      mesenteric schwannoma.

PMID- 24927798
TI  - Molecular mechanism of acute radiation enteritis revealed using proteomics and
      biological signaling network analysis in rats.
AB  - BACKGROUND AND AIMS: Radiation enteritis (RE) has emerged as a significant
      complication that can progress to severe gastrointestinal disease and the
      mechanisms underlying its genesis remain poorly understood. The aim of this study
      was to identify temporal changes in protein expression potentially associated
      with acute inflammation and to elucidate the mechanism underlying radiation
      enteritis genesis. METHODS: Male Sprague-Dawley rats were irradiated in the
      abdomen with a single dose of 10 Gy to establish an in vivo model of acute
      radiation enteritis. Two-dimensional fluorescence difference gel electrophoresis,
      matrix-assisted laser desorption/ionization time-of-flight spectrometer (MALDI
      TOF) tandem mass spectrometry, and peptide mass fingerprinting were used to
      determine differentially expressed proteins between normal and inflamed
      intestinal mucosa. Additionally, differentially expressed proteins were evaluated
      by KO Based Annotation System to find the biological functions associated with
      acute radiation enteritis. RESULTS: Intensity changes of 86 spots were detected
      with statistical significance (ratio >= 1.5 or <= 1.5, P < 0.05). Sixty one of
      the 86 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. These
      radiation-induced proteins with biological functions showed that the FAS pathway
      and glycolysis signaling pathways were significantly altered using the KOBAS
      tool. CONCLUSIONS: Our results reveal an underlying mechanism of radiation
      induced acute enteritis, which may help clarify the pathogenesis of RE and point
      to potential targets for therapeutic interventions.

PMID- 24927800
TI  - Diverticulosis and the risk of interval colorectal cancer.
AB  - BACKGROUND: Diverticulosis, a prevalent condition at screening colonoscopy, has
      been associated with colorectal cancers that develop after a clearing
      colonoscopy, or interval cancers. AIMS: To quantify the overall risk of
      diverticulosis in the development of interval cancers and examine this
      association in relevant subgroups. METHODS: Using a linked database containing
      SEER tumor registry data and Medicare claims, we identified patients aged >=69
      years with colorectal cancer who underwent colonoscopy within 6 months of
      diagnosis. Patients with an additional colonoscopy from 36 to 6 months prior to
      cancer diagnosis were characterized as having interval cancers. We compared
      characteristics of patients with interval cancers and detected cancers according
      to a diagnosis of diverticulosis not associated with a colonoscopy procedure from
      1991 through the date of the most recent colonoscopy in both univariate and
      multivariate models. RESULTS: A previous diagnosis of diverticulosis was
      documented in 14,452 (26.9 %) patients with detected cancers compared to 2,905
      (69.3 %) patients with interval cancers (p < 0.001); these results were
      consistent in multivariable analysis. Moreover, the association was found as well
      in the proximal colon (OR 2.88, 95 % CI 2.66, 3.12), distal colon (OR 3.56, 95 %
      CI 3.09, 4.11), and rectum (OR 4.07, 95 % CI 3.34, 4.95). The vast majority of
      diverticulosis diagnoses were without complications such as hemorrhage or
      diverticulitis. CONCLUSIONS: Diverticulosis was strongly associated with interval
      colorectal cancers in all segments of the colon. Given its known predominance in
      the left colon, the findings argue against impaired visualization of lesions at
      colonoscopy as the only pathogenic factor.

PMID- 24927801
TI  - Endoscopic resection as a first therapy for gastric epithelial atypia: is it
      reasonable?
AB  - BACKGROUND AND AIMS: Gastric atypical cell (GAC), an indefinite pathologic
      finding, often requires repeated biopsy or other diagnostic treatments, such as
      endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or
      operation (OP). The aim of this study was to analyze the initial endoscopic and
      histologic findings of GAC and to discuss the necessity of EMR/ESD at
      establishing a correct diagnosis. METHODS: This retrospective study enrolled 96
      patients proven as GAC on index forceps biopsy. ESD (17/96, 17.7%), EMR (5/96,
      5.2%), OP (20/96, 20.8%), and other treatment or follow-up (54/96, 56.3%) were
      performed. We analyzed the initial endoscopic and histologic characteristics of
      GAC lesions, predictive of neoplasm. RESULTS: After diagnostic modalities, the
      final pathologic diagnoses were cancer (36/96, 37.6%), dysplasia (9/96, 9.4%),
      and non-neoplasm (51/96, 53.0%). In univariate analysis, age [odds ratio (OR)
      1.04, 95% confidence interval (CI) 1.01-1.07], lesion size of 10 mm or greater
      (OR 3.94, 95% CI 1.61-9.61), lesion with depressed type (OR 2.50, 95% CI 1.09
      5.72), and presence of H. pylori (OR 2.83, 95% CI 1.11-7.25) were risk factors
      for neoplasm. In multivariate analysis, lesion size of 10 mm or greater (OR 3.63,
      95% CI 1.23-10.66), lesion with depressed type (OR 2.86, 95% CI 1.11-7.38) were
      independent risk factors for cancer. CONCLUSION: Considering the neoplastic risk
      of GAC, which could be missed on biopsy, more comprehensive tissue sampling via
      EMR/ESD might be necessary to establish a definite diagnosis.

PMID- 24927802
TI  - Information-seeking and sharing behavior following genomic testing for diabetes
      risk.
AB  - As the practice of medicine has become more patient-driven, patients are
      increasingly seeking health information within and outside of their doctor's
      office. Patients looking for information and support are often turning to the
      Internet as well as family and friends. As part of a study to understand the
      impact of delivery method of genomic testing for type 2 diabetes risk on
      comprehension and health-related behaviors, we assessed participants' information
      seeking and sharing behaviors after receiving their results in-person with a
      genetic counselor or online through the testing company's website. We found that
      32.6 % of participants sought information after receiving the genomic test
      results for T2DM; 80.8 % of those that did seek information turned to the
      Internet. Eighty-eight percent of participants reported that they shared their
      T2DM risk results, primarily with their spouse/partner (65 %) and other family
      members (57 %) and children (19 %); 14 % reported sharing results with their
      health provider. Sharing was significantly increased in those who received
      results in-person from the genetic counselor (p = 0.0001). Understanding
      patients' interests and needs for additional information after genomic testing
      and with whom they share details of their health is important as more information
      and clinical services are available and accessed outside the clinician's office.
      Genetic counselors' expertise and experience in creating educational materials
      and promoting sharing of genetic information can facilitate patient engagement
      and education. 

PMID- 24927803
TI  - The link between ethnicity, social disadvantage and mental health problems in a
      school-based multiethnic sample of children in The Netherlands.
AB  - To investigate to what extent differences in prevalence and types of mental
      health problems between ethnic minority and majority youth can be explained by
      social disadvantage. Mental health problems were assessed in a sample of 1,278
      schoolchildren (55% Dutch, 32% Moroccan and 13% Turkish; mean age: 12.9 +/- 1.8)
      using the Strengths and Difficulties Questionnaire self-report and teacher
      report. Measures of family socioeconomic status, neighbourhood deprivation,
      perceived discrimination, family structure, repeating a school year, housing
      stability and neighbourhood urbanization were used as indicators of social
      disadvantage, based on which a cumulative index was created. Ethnic minority
      youth had more externalizing and fewer internalizing problems than majority
      youth. Perceived discrimination and living in an unstable social environment were
      associated with mental health problems, independent of ethnicity. A dose-response
      relationship was found between social disadvantage and mental health problems.
      The adjusted odds ratio for mental health problems was 4.16 (95% CI 2.49-6.94)
      for more than four compared with zero indicators of social disadvantage. Social
      disadvantage was more common in ethnic minority than in majority youth,
      explaining part of the differences in prevalence of mental health problems.
      Ethnic minority youth in the Netherlands have a different profile of mental
      health problems than majority youth. In all ethnic groups, the risk of mental
      health problems increases with the degree of social disadvantage. The higher
      prevalence of externalizing problems among ethnic minority youth is explained
      partly by their disadvantaged social position. The findings suggest that social
      factors associated with ethnicity are likely to explain mental health problems in
      ethnic groups.

PMID- 24927805
TI  - Inequalities in multiple health outcomes by education, sex, and race in 93 US
      counties: why we should measure them all.
AB  - INTRODUCTION: Regular reporting of health inequalities is essential to monitoring
      progress of efforts to reduce health inequalities. While reporting of population
      health became increasingly common, reporting of a subpopulation group breakdown
      of each indicator of the health of the population is rarely a standard practice.
      This study reports education-, sex-, and race-related inequalities in four health
      outcomes in each of the selected 93 counties in the United States in a systematic
      and comparable manner. METHODS: This study is a cross-sectional analysis of
      large, publicly available data, 2008, 2009, and 2010 Behavioral Risk Factor
      Surveillance System (BRFSS) Selected Metropolitan/Micropolitan Area Risk Trends
      (SMART) and 2008, 2009, and 2010 United States Birth Records from the National
      Vital Statistics System. The study population is American adults older than 25
      years of age residing in the selected 93 counties, representing about 30% of the
      US population, roughly equally covering all geographic regions of the country.
      Main outcome measures are: (1) Attribute (group characteristic)-specific
      inequality: education-, sex-, or race-specific inequality in each of the four
      health outcomes (poor or fair health, poor physical health days, poor mental
      health days, and low birthweight) in each county; (2) Overall inequality: the
      average of these three attribute-specific inequalities for each health outcome in
      each county; and (3) Summary inequality in total morbidity: the weighted average
      of the overall inequalities across the four health outcomes in each county.
      RESULTS: The range of inequality across the counties differed considerably by
      health outcome; inequality in poor or fair health had the widest range and the
      highest median among inequalities in all health outcomes. In more than 70% of the
      counties, education-specific inequality was the largest in all health outcomes
      except for low birthweight. CONCLUSIONS: It is feasible to extend population
      health reporting to include reporting of a subpopulation group breakdown of each
      indicator of the health of the population at a small jurisdictional level using
      publicly available data. No single group characteristic or health outcome
      represents the whole picture of health inequalities in a population. Examining
      multiple group characteristics and outcomes in a comparable manner is essential
      in reporting health inequalities.

PMID- 24927806
TI  - Vascular and interventional radiology radiofrequency ablation of benign thyroid
      nodules and recurrent thyroid cancers: literature review.
AB  - Thermal radiofrequency ablation is a relatively new, minimally invasive modality
      employed as an alternative to surgery in patients with benign thyroid nodules and
      recurrent thyroid cancers. Different recommendations are necessary for the
      optimal use of radiofrequency ablation for thyroid nodules. These recommendations
      are based on a comprehensive analysis of the current literature, the results of
      multicenter studies, and expert consensus. 

PMID- 24927807
TI  - Vitamin d in the general population of young adults with autism in the faroe
      islands.
AB  - Vitamin D deficiency has been proposed as a possible risk factor for developing
      autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were
      examined in a cross-sectional population-based study in the Faroe Islands. The
      case group consisting of a total population cohort of 40 individuals with ASD
      (aged 15-24 years) had significantly lower 25(OH)D3 than their 62 typically
      developing siblings and their 77 parents, and also significantly lower than 40
      healthy age and gender matched comparisons. There was a trend for males having
      lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various
      subcategories of ASD and Autism Diagnostic Observation Schedule score were also
      investigated, however, no association was found. The very low 25(OH)D3 in the ASD
      group suggests some underlying pathogenic mechanism. 

PMID- 24927808
TI  - Irradiated tumor cells of lipopolysaccharide stimulation elicit an enhanced anti
      tumor immunity.
AB  - PURPOSE: Lipopolysaccharide (LPS) is a major component of the outer surface
      membrane of Gram-negative bacteria which has been proved an effective immune
      enhancer. Here, we investigated the anti-tumor effect of irradiated tumor cells
      that stimulated by LPS in mouse xenografts models. METHODS: Tumor cells were
      irradiated after stimulation with 1 MUg/mL LPS for 48 h. The C57BL/6 mice were
      immunized subcutaneously with irradiated tumor cells. The anti-tumor effect of
      lymphocytes of immunized mice was investigated. The cytotoxicity of spleen
      lymphocytes from immunized mice was determined by a standard (51)Cr-release
      assay. The roles of immune cell subsets in anti-tumor activity were assessed by
      injected intraperitoneally with monoclonal antibodies. RESULTS: We observed that
      the vaccine of irradiated tumor cell with LPS-stimulated elicited a stronger
      protective anti-tumor immunity than other controls. Adoptive transfer of
      lymphocytes of immunized mice showed that the cellular immune response was
      involved in the anti-tumor effect. And this effect was achieved by activation of
      antigen-specific CD8(+) T cell response and reduction of myeloid-derived
      suppressor cells (MDSCs, Gr1(+) CD11b (+) ), which were confirmed by depletion of
      immune cell subsets and flow cytometry analysis. CONCLUSIONS: In summary, our
      study showed that stimulation of LPS was able to enhance anti-tumor immunity of
      vaccination with tumor cells after irradiation treatment, which might be a new
      strategy for cancer therapy.

PMID- 24927810
TI  - The threat of the dyscompetent resident: A plea to make the implicit more
      explicit!
AB  - Although several examples of frameworks dealing with students' unprofessional
      behaviour are available, guidance on how to deal locally or regionally with
      dysfunctional residents is limited (Hickson et al. in Acad Med 82(11):1040-1048,
      2007b; Leape and Fromson in Ann Intern Med 144(2):107-115, 2006). Any 'rules' are
      mostly unwritten, and often emerge by trial and error within the specialty
      training programme (Stern and Papadakis in N Engl J Med 355(17):1794-1799, 2006).
      It is nevertheless of utmost importance that objectives, rules and guidelines
      comparable to those existing in undergraduate training (Project Team Consilium
      Abeundi van Luijk in Professional behaviour: teaching, assessing and coaching
      students. Final report and appendices. Mosae Libris, 2005; van Mook et al. in
      Neth J Crit Care 16(4):162-173, 2010a) are developed for postgraduate training.
      And that implicit rules are made explicit. This article outlines a framework
      based on the lessons learned from contemporary postgraduate medical training
      programmes.

PMID- 24927809
TI  - Cultivation of Rickettsia amblyommii in tick cells, prevalence in Florida lone
      star ticks (Amblyomma americanum).
AB  - BACKGROUND: Rickettsia amblyommii is a bacterium in the spotted fever group of
      organisms associated with the lone star tick (LST), Amblyomma americanum. The LST
      is the most commonly reported tick to parasitize humans in the southeastern US.
      Within this geographic region, there have been suspected cases of Rocky Mountain
      spotted fever (RMSF) where the causative agent, R. rickettsii, was not identified
      in the local tick population. In these areas, patients with clinical signs of
      RMSF had low or no detectable antibodies to R. rickettsii, resulting in an
      inability to confirm a diagnosis. METHODS: R. amblyommii was cultivated from host
      seeking LSTs trapped in Central Florida and propagated in ISE6 (Ixodes
      scapularis) and AAE2 (A. americanum) cells. Quantitative PCR targeting the 17-kD
      gene of Rickettsia spp. identified the genus of the organism in culture. Variable
      regions of groEL, gtlA and rompA genes were amplified and sequenced to confirm
      the species. The prevalence of R. amblyommii in LSTs within the geographic region
      was determined by qPCR followed by conventional PCR and direct sequencing.
      RESULTS: Analyses of amplified sequences from the cultured organism were 100%
      homologous to R. amblyommii. The overall prevalence of Rickettsia spp. in the
      local population of LSTs was 57.1% and rompA sequence analysis identified only R.
      amblyommii in LSTs. CONCLUSIONS: A Florida strain of R. amblyommii was
      successfully cultivated in two tick cell lines. Further evaluation of the new
      strain and comparisons to the other geographic strains is needed. The prevalence
      of this SFG organism in the tick population warrants further investigation into
      the organism's ability to cause clinical disease in mammalian species.

PMID- 24927811
TI  - A prospective observational study to assess the diagnostic accuracy of clinical
      decision rules for children presenting to emergency departments after head
      injuries (protocol): the Australasian Paediatric Head Injury Rules Study
      (APHIRST).
AB  - BACKGROUND: Head injuries in children are responsible for a large number of
      emergency department visits. Failure to identify a clinically significant
      intracranial injury in a timely fashion may result in long term neurodisability
      and death. Whilst cranial computed tomography (CT) provides rapid and definitive
      identification of intracranial injuries, it is resource intensive and associated
      with radiation induced cancer. Evidence based head injury clinical decision rules
      have been derived to aid physicians in identifying patients at risk of having a
      clinically significant intracranial injury. Three rules have been identified as
      being of high quality and accuracy: the Canadian Assessment of Tomography for
      Childhood Head Injury (CATCH) from Canada, the Children's Head Injury Algorithm
      for the Prediction of Important Clinical Events (CHALICE) from the UK, and the
      prediction rule for the identification of children at very low risk of clinically
      important traumatic brain injury developed by the Pediatric Emergency Care
      Applied Research Network (PECARN) from the USA. This study aims to prospectively
      validate and compare the performance accuracy of these three clinical decision
      rules when applied outside the derivation setting. METHODS/DESIGN: This study is
      a prospective observational study of children aged 0 to less than 18 years
      presenting to 10 emergency departments within the Paediatric Research in
      Emergency Departments International Collaborative (PREDICT) research network in
      Australia and New Zealand after head injuries of any severity. Predictor
      variables identified in CATCH, CHALICE and PECARN clinical decision rules will be
      collected. Patients will be managed as per the treating clinicians at the
      participating hospitals. All patients not undergoing cranial CT will receive a
      follow up call 14 to 90 days after the injury. Outcome data collected will
      include results of cranial CTs (if performed) and details of admission,
      intubation, neurosurgery and death. The performance accuracy of each of the rules
      will be assessed using rule specific outcomes and inclusion and exclusion
      criteria. DISCUSSION: This study will allow the simultaneous comparative
      application and validation of three major paediatric head injury clinical
      decision rules outside their derivation setting. TRIAL REGISTRATION: The study is
      registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)-
      ACTRN12614000463673 (registered 2 May 2014).

PMID- 24927812
TI  - A multi-year assessment of the environmental impact of transgenic Eucalyptus
      trees harboring a bacterial choline oxidase gene on biomass, precinct vegetation
      and the microbial community.
AB  - A 4-year field trial for the salt tolerant Eucalyptus globulus Labill. harboring
      the choline oxidase (codA) gene derived from the halobacterium Arthrobacter
      globiformis was conducted to assess the impact of transgenic versus non
      transgenic trees on biomass production, the adjacent soil microbial communities
      and vegetation by monitoring growth parameters, seasonal changes in soil microbes
      and the allelopathic activity of leaves. Three independently-derived lines of
      transgenic E. globulus were compared with three independent non-transgenic lines
      including two elite clones. No significant differences in biomass production were
      detected between transgenic lines and non-transgenic controls derived from same
      seed bulk, while differences were seen compared to two elite clones. Significant
      differences in the number of soil microbes present were also detected at
      different sampling times but not between transgenic and non-transgenic lines. The
      allelopathic activity of leaves from both transgenic and non-transgenic lines
      also varied significantly with sampling time, but the allelopathic activity of
      leaves from transgenic lines did not differ significantly from those from non
      transgenic lines. These results indicate that, for the observed variables, the
      impact on the environment of codA-transgenic E. globulus did not differ
      significantly from that of the non-transformed controls on this field trial. 

PMID- 24927814
TI  - Unusual implant-related soft tissue reaction presenting as a swollen leg: a case
      report.
AB  - INTRODUCTION: There are several causes of peri-implant edema, pain, and swelling
      around implants after orthopedic fixation device application for fracture repair.
      The most common and well-known reason is infection, however, granulomas
      associated with foreign body reactions are rarely seen. In this report we present
      a case of a granulomatous reaction mimicking a hydatid cyst and sarcoma. We
      emphasize the importance of differential diagnosis in triggering appropriate
      management of the patient. Our case was unusual; to the best of our knowledge no
      similar clinical or pathological findings have been reported in current
      literature. CASE PRESENTATION: A 56-year-old Turkish man who had been treated for
      a right femoral fracture via a plate fixation 10 years prior underwent an
      operation to treat pain and swelling around the plate. A hydatid cyst-like mass
      was observed during surgery, but subsequent examination revealed that no hydatid
      cyst was present; both malignancy and infection were also absent. CONCLUSIONS:
      Although infection is generally the first possibility that should be considered
      in a patient complaining of pain and swelling in the vicinity of an implant,
      malignancies, hydatid cysts, and (finally) foreign body reactions should also be
      kept in mind as differential diagnoses. A soft-tissue reaction around a
      previously implanted plate should be managed carefully. Pre-operative
      radiological assessment, and biopsy to allow pathological and microbiological
      examination, should be considered in all suspected cases.

PMID- 24927813
TI  - Genetic inhibition of the atypical kinase Wee1 selectively drives apoptosis of
      p53 inactive tumor cells.
AB  - BACKGROUND: Tumorigenesis is the result of genomic or epigenomic insults and
      subsequent loss of the proper mechanisms to respond to these alterations leading
      to unscheduled growth. Tumors arising from these mutations often have altered
      cell cycles that offer proliferative advantages and lead to the accumulation of
      additional mutations that can lead to more aggressive phenotypes. Nevertheless,
      tumor cells must still adhere to the basic tenets of the cell cycle program to
      ensure their survival by DNA duplication, chromosomal segregation and
      cytokinesis. The atypical tyrosine kinase Wee1 plays a key role in regulating the
      cell cycle at the DNA synthesis and mitotic checkpoints via phosphorylation and
      subsequent inactivation of cyclin-dependent kinases (CDKs) in both healthy and
      tumorigenic cells. METHODS: To assess the role of Wee1 in tumor cell
      proliferation we performed small interfering RNA (siRNA) experiments in a panel
      of diverse cell lines derived from various tissue origins. We also tested the
      hypothesis that any potential effects would be as a result of the kinase activity
      of Wee1 by siRNA rescue studies with wild-type or kinase-dead versions of Wee1.
      RESULTS: We find that, in general, cells with wild-type p53 activity are not
      susceptible to loss of Wee1 protein via siRNA. However, Wee1 siRNA treatment in
      tumor cells with an inherent loss of p53 activity results in a deregulated cell
      cycle that causes simultaneous DNA synthesis and premature mitosis and that these
      effects are kinase dependent. These cumulative effects lead to potent inhibition
      of cellular proliferation and ultimately caspase-dependent apoptosis in the
      absence of co-treatment with cytotoxic agents. CONCLUSIONS: These results suggest
      that, while Wee1 acts as a tumor suppressor in the context of normal cell growth
      and its functional loss can be compensated by p53-dependent DNA damage repairing
      mechanisms, specific inhibition of Wee1 has deleterious effects on the
      proliferation and survival of p53 inactive tumors. In total, targeting the
      atypical kinase Wee1 with an siRNA-based therapeutic or a selective ATP
      competitive small molecule inhibitor would be a feasible approach to targeting
      p53 inactive tumors in the clinic.

PMID- 24927815
TI  - Liquid oral suspension adefovir dipivoxil (GS-02-526): an update on treatments
      for hepatitis B infection.
AB  - Though the global epidemiology of hepatitis B virus infection has declined due to
      effective immunization, chronic hepatitis B (CHB) remains a serious public health
      problem and there is still a need for more treatment options that are efficient,
      safe and simple for different kinds of CHB patients. Adefovir dipivoxil (ADV)
      liquid suspension (GS-02-526), as a new form of oral ADV, not only has competent
      antiviral efficacy, but is also more convenient for patients with swallowing
      difficulties or patients with impaired renal function requiring dosage
      adjustment. The clinical data evaluating the safety, tolerability and antiviral
      activity of liquid suspension of ADV as well as its tablet are summarized in this
      article. The availability of liquid oral suspension of ADV would allow more
      patients to receive timely and reasonable antiviral treatments. 

PMID- 24927816
TI  - Strengthening the capacity of managers in pharmaceutical services based on
      Primary Health Care (PHC) at different levels of the health system.
AB  - INTRODUCTION: Distance learning methods have been widely used because of their
      advantages to continuing professional development processes. The Primary Health
      Care (PHC) is a strategy which has been implemented in order to improve the
      efficiency of health systems. Due to the need for access to medicines and
      technologies regardless of the strengthening of health systems, a new approach
      that better integrates both pharmaceutical services and health systems has been
      implemented. CASE DESCRIPTION: This is a case study which consists of describing
      the process of restructuring, developing and implementing the second version of
      the Virtual Course on Primary Health Care-based Pharmaceutical Services for
      managers (CVSERVFAPS-12). The main objective is to strengthen the capacity of
      managers in pharmaceutical services, based on PHC at different levels of the
      health system, in order to support the restructuring and empowering of these
      services and, consequently, the health systems in the American region. DISCUSSION
      AND EVALUATION: Many evaluation tools were applied to identify the
      achievement/improvement of planned competencies. The intervention proposals were
      collectively built and intended to be more than an academic exercise, looking
      forward to being implemented as a strategic intervention to promote changes in
      the pharmaceutical services of the American region. The main strengths identified
      for the second version of the course were related to the quality of the didactic
      material and content. Additionally, the tutors' support was commented upon as a
      positive aspect. The main challenges faced in this rebuilding process related to
      the due dates of the activities and lectures as well as the time to capture and
      assimilate the content. CONCLUSIONS: The CVSERVFAPS-Pilot was reformulated and
      CVSERVFAPS-12 is consistent with the issues raised in the pilot course's
      evaluation in 2011, which were successfully implemented. The use of the distance
      learning strategy, through a virtual environment, for the application of the
      Virtual Course on PHC- based pharmaceutical services for managers, is appropriate
      and confirmed its role in public policy promotion through effective retention and
      distribution of health workers.

PMID- 24927817
TI  - Improving analysis of transcription factor binding sites within ChIP-Seq data
      based on topological motif enrichment.
AB  - BACKGROUND: Chromatin immunoprecipitation (ChIP) coupled to high-throughput
      sequencing (ChIP-Seq) techniques can reveal DNA regions bound by transcription
      factors (TF). Analysis of the ChIP-Seq regions is now a central component in gene
      regulation studies. The need remains strong for methods to improve the
      interpretation of ChIP-Seq data and the study of specific TF binding sites
      (TFBS). RESULTS: We introduce a set of methods to improve the interpretation of
      ChIP-Seq data, including the inference of mediating TFs based on TFBS motif over
      representation analysis and the subsequent study of spatial distribution of
      TFBSs. TFBS over-representation analysis applied to ChIP-Seq data is used to
      detect which TFBSs arise more frequently than expected by chance. Visualization
      of over-representation analysis results with new composition-bias plots reveals
      systematic bias in over-representation scores. We introduce the BiasAway
      background generating software to resolve the problem. A heuristic procedure
      based on topological motif enrichment relative to the ChIP-Seq peaks' local
      maximums highlights peaks likely to be directly bound by a TF of interest. The
      results suggest that on average two-thirds of a ChIP-Seq dataset's peaks are
      bound by the ChIP'd TF; the origin of the remaining peaks remaining undetermined.
      Additional visualization methods allow for the study of both inter-TFBS spatial
      relationships and motif-flanking sequence properties, as demonstrated in case
      studies for TBP and ZNF143/THAP11. CONCLUSIONS: Topological properties of TFBS
      within ChIP-Seq datasets can be harnessed to better interpret regulatory
      sequences. Using GC content corrected TFBS over-representation analysis, combined
      with visualization techniques and analysis of the topological distribution of
      TFBS, we can distinguish peaks likely to be directly bound by a TF. The new
      methods will empower researchers for exploration of gene regulation and TF
      binding.

PMID- 24927818
TI  - Characterization of tau oligomeric seeds in progressive supranuclear palsy.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy
      which is primarily defined by the deposition of tau into globose-type
      neurofibrillary tangles (NFT). Tau in its native form has important functions for
      microtubule dynamics. Tau undergoes alternative splicing in exons 2, 3, and 10
      which results in six different isoforms. Products of splicing on exon 10 are the
      most prone to mutations. Three repeat (3R) and four repeat (4R) tau, like other
      disease-associated amyloids, can form oligomers which may then go on to further
      aggregate and form fibrils. Recent studies from our laboratory and others have
      provided evidence that tau oligomers, not NFTs, are the most toxic species in
      neurodegenerative tauopathies and seed the pathological spread of tau. RESULTS:
      Analysis of PSP brain sections revealed globose-type NFTs, as well as both
      phosphorylated and unphosphorylated tau oligomers. Analysis of PSP brains via
      Western blot and ELISA revealed the presence of increased levels of tau oligomers
      compared to age-matched control brains. Oligomers were immunoprecipitated from
      PSP brain and were capable of seeding the oligomerization of both 3R and 4R tau
      isoforms. CONCLUSIONS: This is the first time tau oligomers have been
      characterized in PSP. These results indicate that tau oligomers are an important
      component of PSP pathology, along with NFTs. The ability of PSP brain-derived tau
      oligomers to seed 3R and 4R tau suggests that these oligomers represent the
      pathological species responsible for disease propagation and the presence of
      oligomers in a pure neurodegenerative tauopathy implies a common
      neuropathological process for tau seen in diseases with other amyloid proteins.

PMID- 24927819
TI  - National targets, process transformation and local consequences in an NHS
      emergency department (ED): a qualitative study.
AB  - BACKGROUND: In the attempt to reduce waiting times in emergency departments,
      various national health services have used benchmarking and the optimisation of
      patient flows. The aim of this study was to examine staff attitudes and
      experience of providing emergency care following the introduction of a 4 hour
      wait target, focusing on clinical, organisational and spatial issues. METHODS: A
      qualitative research design was used and semi-structured interviews were
      conducted with 28 clinical, managerial and administrative staff members working
      in an inner-city emergency department. A thematic analysis method was employed
      and NVivo 8 qualitative data analysis software was used to code and manage the
      emerging themes. RESULTS: The wait target came to regulate the individual and
      collective timescales of healthcare work. It has compartmentalised the previous
      unitary network of emergency department clinicians and their workspace. It has
      also speeded up clinical performance and patient throughput. It has disturbed
      professional hierarchies and facilitated the development of new professional
      roles. A new clinical information system complemented these reconfigurations by
      supporting advanced patient tracking, better awareness of time, and continuous,
      real-time management of emergency department staff. The interviewees had concerns
      that this target-oriented way of working forces them to have a less personal
      relationship with their patients. CONCLUSIONS: The imposition of a wait-target in
      response to a perceived "crisis" of patients' dissatisfaction led to the
      development of a new and sophisticated way of working in the emergency
      department, but with deep and unintended consequences. We show that there is a
      dynamic interrelation of the social and the technical in the complex environment
      of the ED. While the 4 hour wait target raised the profile of the emergency
      department in the hospital, the added pressure on clinicians has caused some
      concerns over the future of their relationships with their patients and
      colleagues. To improve the sustainability of such sudden changes in policy
      direction, it is important to address clinicians' experience and satisfaction.

PMID- 24927820
TI  - Whole-genome QTL analysis for MAGIC.
AB  - KEY MESSAGE: An efficient whole genome method of QTL analysis is presented for
      Multi-parent advanced generation integrated crosses. Multi-parent advanced
      generation inter-cross (MAGIC) populations have been developed for mice and
      several plant species and are useful for the genetic dissection of complex
      traits. The analysis of quantitative trait loci (QTL) in these populations
      presents some additional challenges compared with traditional mapping approaches.
      In particular, pedigree and marker information need to be integrated and founder
      genetic data needs to be incorporated into the analysis. Here, we present a
      method for QTL analysis that utilizes the probability of inheriting founder
      alleles across the whole genome simultaneously, either for intervals or markers.
      The probabilities can be found using three-point or Hidden Markov Model (HMM)
      methods. This whole-genome approach is evaluated in a simulation study and it is
      shown to be a powerful method of analysis. The HMM probabilities lead to low
      rates of false positives and low bias of estimated QTL effect sizes. An
      implementation of the approach is available as an R package. In addition, we
      illustrate the approach using a bread wheat MAGIC population.

PMID- 24927821
TI  - Marker-assisted introgression of a QTL region to improve rust resistance in three
      elite and popular varieties of peanut (Arachis hypogaea L.).
AB  - KEY MESSAGE: Successful introgression of a major QTL for rust resistance, through
      marker-assisted backcrossing, in three popular Indian peanut cultivars generated
      several promising introgression lines with enhanced rust resistance and higher
      yield. Leaf rust, caused by Puccinia arachidis Speg, is one of the major
      devastating diseases in peanut (Arachis hypogaea L.). One QTL region on linkage
      group AhXV explaining upto 82.62 % phenotypic variation for rust resistance was
      validated and introgressed from cultivar 'GPBD 4' into three rust susceptible
      varieties ('ICGV 91114', 'JL 24' and 'TAG 24') through marker-assisted
      backcrossing (MABC). The MABC approach employed a total of four markers including
      one dominant (IPAHM103) and three co-dominant (GM2079, GM1536, GM2301) markers
      present in the QTL region. After 2-3 backcrosses and selfing, 200 introgression
      lines (ILs) were developed from all the three crosses. Field evaluation
      identified 81 ILs with improved rust resistance. Those ILs had significantly
      increased pod yields (56-96 %) in infested environments compared to the
      susceptible parents. Screening of selected 43 promising ILs with 13 markers
      present on linkage group AhXV showed introgression of the target QTL region from
      the resistant parent in 11 ILs. Multi-location field evaluation of these ILs
      should lead to the release of improved varieties. The linked markers may be used
      in improving rust resistance in peanut breeding programmes.

PMID- 24927822
TI  - Effects of stacked quantitative resistances to downy mildew in lettuce do not
      simply add up.
AB  - KEY MESSAGE: In a stacking study of eight resistance QTLs in lettuce against
      downy mildew, only three out of ten double combinations showed an increased
      resistance effect under field conditions. Complete race nonspecific resistance to
      lettuce downy mildew, as observed for the nonhost wild lettuce species Lactuca
      saligna, is desired in lettuce cultivation. Genetic dissection of L. saligna's
      complete resistance has revealed several quantitative loci (QTL) for resistance
      with field infection reductions of 30-50 %. To test the effect of stacking these
      QTL, we analyzed interactions between homozygous L. saligna CGN05271 chromosome
      segments introgressed into the genetic background of L. sativa cv. Olof. Eight
      different backcross inbred lines (BILs) with single introgressions of 30-70 cM
      and selected predominately for quantitative resistance in field situations were
      intercrossed. Ten developed homozygous lines with stacked introgression segments
      (double combinations) were evaluated for resistance in the field. Seven double
      combinations showed a similar infection as the individual most resistant parental
      BIL, revealing epistatic interactions with 'less-than-additive' effects. Three
      double combinations showed an increased resistance level compared to their
      parental BILs and their interactions were additive, 'less-than-additive'
      epistatic and 'more-than-additive' epistatic, respectively. The additive
      interaction reduced field infection by 73 %. The double combination with a 'more
      than-additive' epistatic effect, derived from a combination between a susceptible
      and a resistant BIL with 0 and 30 % infection reduction, respectively, showed an
      average field infection reduction of 52 %. For the latter line, an attempt to
      genetically dissect its underlying epistatic loci by substitution mapping did not
      result in smaller mapping intervals as none of the 22 substitution lines reached
      a similar high resistance level. Implications for breeding and the inheritance of
      L. saligna's complete resistance are discussed.

PMID- 24927823
TI  - Enantioselective one-pot synthesis of dihydroquinolones via BINOL-derived Lewis
      acid catalysis.
AB  - A high-yielding and diastereoselective route to biologically significant 2-aryl-
      and 2-alkyl-3-amido dihydroquinolones has been developed in up to 90 : 10 e.r. by
      employing a novel Lewis acidic BINOL-derived copper(ii) catalyst. 

PMID- 24927824
TI  - cGMP: transition from bench to bedside: a report of the 6th International
      Conference on cGMP Generators, Effectors and Therapeutic Implications.
AB  - Essential physiological homeostatic processes such as vascular tone, fluid
      balance, cardiorenal function, and sensory processes are regulated by the second
      messenger cyclic guanosine 3', 5'-monophosphate (cGMP). Dysregulation of cGMP
      dependent pathways plays an important role in cardiovascular diseases such as
      hypertension, pulmonary hypertension, heart failure, or erectile dysfunction.
      Thus, the cGMP pathway consisting of the cGMP-generating guanylyl cyclases,
      protein kinases, and phosphodiesterases (PDE) has evolved to an important drug
      target and is the focus of a wide variety of research fields ranging from
      unraveling mechanisms on the molecular level to understanding the regulation of
      physiological and pathophysiological processes by cGMP. Based on the results from
      basic and preclinical research, therapeutic drugs have been developed which
      modulate the cGMP pathway and are investigated in clinical trials. Riociguat, a
      nitric oxide (NO)-independent soluble guanylyl cyclase stimulator; recombinant B
      type natriuretic peptide (BNP); or recombinant atrial natriuretic peptide (ANP)
      and PDE5 inhibitors are cGMP-modulating drugs that are already available for the
      treatment of pulmonary hypertension, acute heart failure, and erectile
      dysfunction, respectively. The latest results from basic to clinical research on
      cGMP were presented on the 6th International Conference on cGMP in Erfurt,
      Germany, and are summarized in this article. 

PMID- 24927826
TI  - Biologically-related or emotionally-connected: who would be the better surrogate
      decision-maker?
AB  - As an incapacitated patient is unable to make decisions regarding their care,
      physicians turn to next-of-kin when appointing a surrogate decision-maker in the
      absence of an advanced directive. With the increasing complexity of modern
      families, physicians are facing new ethical dilemmas when choosing the individual
      to make end-of-life decisions for their patients. Legal definitions and
      hierarchies are no longer adhering to the purpose of a surrogate-decision maker,
      which is to maintain a patient's autonomy. Moral criteria for surrogates, which
      emphasize the importance of making decisions that align with the patient's
      desires and wishes and negate biological relationships over emotional
      connections, are becoming much more important. This paper explores a case study
      in which physicians must appoint a surrogate decision-maker for an incapacitated
      patient, forced to choose between a biological relationship and a strong
      emotional connection. 

PMID- 24927825
TI  - Neurocognitive impairment associated with predominantly early stage HIV infection
      in Abuja, Nigeria.
AB  - Detailed neuropsychological testing was performed on 133 human immunodeficiency
      virus (HIV) seropositive (SP) and 77 HIV seronegative (SN) individuals, 86 % with
      early stage HIV infection in Nigeria, to determine the frequency of HIV-related
      neurocognitive impairment among the HIV-infected group. The tests were
      administered to assess the following seven ability domains: speed of information
      processing, attention/working memory, executive functioning, learning, memory,
      verbal fluency, and motor function motor. Demographically corrected individual
      test scores and scores for each domain or reflecting a global deficit (a global
      deficit score, or GDS) were compared for the SP and SN groups. SP participants
      were older, had fewer years of education, were more likely to be married,
      differed in ethnicity, and had higher depression scores than SN individuals.
      Within the seven ability domains, SP performed worse than SN with respect to
      speed of information processing, executive function, learning, memory, and verbal
      fluency and also on the global measure. SP were also more frequently impaired on
      tests of SIP, and there was a borderline increase in the frequency of global
      impairment. On the individual tests, SP performed worse than SN on four tests
      that assessed learning, verbal fluency, memory, and motor function (the Timed
      Gait). SP subjects, however, performed better than SN on the Finger-tapping test,
      also a motor task. Performance by SP subjects was not associated on the timed
      gait which showed a borderline statistically significant correlation with CD4
      counts. However, there were significant correlations between viral load
      measurements and individual tests of speed of information processing, executive
      function, learning, and verbal fluency and with overall executive function and a
      borderline correlation with the GDS. Depression scores for SP were associated
      with impairment on only a single test of executive function. These results
      demonstrate the ability of these assessments to identify areas of impairment that
      may be specifically linked to a history of HIV infection among individuals in
      Nigeria. Confirmation of these findings awaits analyses using data from a larger
      number of control subjects.

PMID- 24927827
TI  - Effects of repetitive exposure to anesthetics and analgesics in the Tg2576 mouse
      Alzheimer's model.
AB  - The use of anesthetics and sedatives has been suggested to be a contributor to
      Alzheimer's disease neuropathogenesis. We wanted to address the in vivo relevance
      of those substances in the Tg2576 Alzheimer's mouse model. Tg7526 mice were
      anesthesia-sedated for 90 min once a week for 4 weeks. Y maze, Congo Red, and
      amyloid beta (Abeta) immunochemistry were performed. We did not find any
      significant change in the navigation behavior of the exposed mice compared to the
      controls. Significantly less deposition of Abeta in the CA1 area of the
      hippocampus and frontal cortex of mice exposed to isoflurane, propofol, diazepam,
      ketamine, and pentobarbital was observed. In the dentate gyrus, Abeta deposition
      was significantly greater in the group treated with pentobarbital. Congo Red
      staining evidenced significantly fewer fibrils in the cortex of mice exposed to
      diazepam, ketamine, or pentobarbital. The adopted repetitive exposure did not
      cause a significant detriment in Tg7526 mouse. 

PMID- 24927828
TI  - Absorbable and nonabsorbable packing after functional endoscopic sinus surgery:
      systematic review and meta-analysis of outcomes.
AB  - The purpose of the study was to perform a systematic review and meta-analysis of
      the literature to compare the efficacy (and other postoperative outcomes) of
      nonabsorbable versus absorbable nasal packing after functional endoscopic sinus
      surgery (FESS) for the treatment of chronic rhinosinusitis. Studies were
      considered for inclusion if they were published in English language, were
      randomized clinical trials, and reported on outcomes following postoperative
      synechia. The primary outcome for meta-analysis was the incidence of
      postoperative synechia; pooled odds ratios (ORs) and 95 % confidence intervals
      (CIs) were calculated using fixed-effects models. Five studies, involving 241
      nasal cavities in each treatment group, were included in the systematic review.
      The prevalence of synechia ranged from 4.6 to 8.0 % in the absorbable groups and
      from 8.0 to 35.7 % in the nonabsorbable groups. Postoperative bleeding was lower
      in the absorbable groups, whereas there was no clear finding regarding
      postoperative pain. Postoperative edema was generally similar between groups.
      There were no consistent findings regarding bleeding and pain on packing removal.
      Two studies using the same type of packing material were included in the meta
      analysis. The combined OR (0.33, 95 % CI 0.04-2.78) for postoperative synechia
      did not significantly favor (P = 0.308) absorbable packing over nonabsorbable
      packing. Although there is some evidence in the available literature that
      absorbable nasal packing may provide superior outcomes to nonabsorbable packing
      after FESS, the lack of homogeneity between studies makes definitive conclusions
      impossible. Further randomized clinical trials are needed to compare the efficacy
      of different types of absorbable nasal packing for preventing synechia after
      FESS.

PMID- 24927829
TI  - Facial and lower cranial nerve function preservation in lateral approach for
      craniocervical schwannomas.
AB  - The purpose of this study was to discuss surgical approach selection, surgical
      procedures, and treatment strategy for preservation of the facial and lower
      cranial nerve function in craniocervical schwannomas surgery. Between 2002 and
      2011, 44 craniocervical schwannomas were operated in Xinhua hospital of Shanghai,
      China by the same surgical team. The records were reviewed retrospectively
      regarding clinical presentation, radiographic assessment, surgical approaches
      selection, surgical procedures and facial and lower cranial nerve follow-up
      outcomes. Headache or neck pain was present in 30 patients (68.2 %) and cervical
      mass in 9 patients (20.5 %). Cranial nerve impairments, mainly involving the
      vagus nerve, were present in 19 patients (43.2 %) and hypoglossal nerve in five
      patients (11.4 %). 22 tumors were intra- and extracranial, 10 were intra-cranial
      and 12 were extra-cranial. According to the tumor region, infratemporal fossa
      type A approach, petrous occipital transsigmoid approach and transcervial
      approach were selected for tumor removal. Gross-total resection was achieved in
      40 patients (90.9 %). Adjunctive radiosurgery was used in the management of
      residual tumor in two patients; tumor control was ultimately obtained in all
      cases. During follow-up period, good facial function was obtained in 42 patients
      (95.5 %) and complete compensation of lower cranial nerve function was achieved
      in all patients. The preoperative estimation of tumor in nature is of great
      importance in the determination of proper surgical planning of craniaocervical
      schwannomas. Facial nerve and lower cranial nerve function can be preserved in
      maximal degree by proper surgical approaches and careful operative manipulation.
      Initial surgical resection followed by radiosurgery may be an effective option
      for some special patients.

PMID- 24927830
TI  - Detecting protein-protein interactions/complex components using mass spectrometry
      coupled techniques.
AB  - Proteins play important roles in biochemical processes. Most biological functions
      are realized through protein-protein interactions (PPI). Co-immunoprecipitation
      is the most straightforward method to detect PPI. With the development of modern
      mass spectrometry (MS), throughput, sensitivity, and confidence for the detection
      of PPI can be readily achieved by scaling up traditional antibody-based
      strategies. Herein, we describe a typical workflow for general PPI detection
      using mass spectrometry coupled techniques, covering from Co-immunoprecipitation
      (Co-IP), to gel display, in-gel digestion, liquid chromatography mass
      spectrometry (LC-MS) analysis, as well as result interpretation and statistic
      filtering. This protocol provides an overview of the technique as well as
      practical tips. 

PMID- 24927831
TI  - Analysis of transcription factor networks using IVV method.
AB  - We have developed a simple and totally in vitro selection procedure based on cell
      free cotranslation using a highly stable and efficient in vitro virus (IVV). Cell
      free cotranslation of tagged bait and prey proteins is advantageous for the
      formation of protein complexes and allows high-throughput analysis of protein
      protein interactions (PPI) as a result of providing in vitro instead of in vivo
      preparation of bait proteins. The use of plural selection rounds and a two-step
      purification of the IVV selection, followed by in vitro post-selection, is
      advantageous for decreasing false positives. This simple IVV selection system
      based on cell-free cotranslation is applicable to high-throughput and
      comprehensive analysis of transcription factor networks. 

PMID- 24927832
TI  - Next-generation sequencing coupled with a cell-free display technology for
      reliable interactome of translational factors.
AB  - Next-generation sequencing (NGS) has been applied to various kinds of omics
      studies, resulting in many biological and medical discoveries. However, high
      throughput protein-protein interactome datasets derived from detection by
      sequencing are scarce, because protein-protein interaction analysis requires many
      cell manipulations to examine the interactions. The low reliability of the high
      throughput data is also a problem. Here, we describe a cell-free display
      technology combined with NGS that can improve both the coverage and reliability
      of interactome datasets. This in vitro method is suitable for exploring the
      interactome networks of transcription factors. 

PMID- 24927833
TI  - Chromatin immunoprecipitation protocol for mammalian cells.
AB  - The genomic approach (ChIP-seq) we introduce here is now a widely used powerful
      tool to explore protein-DNA interaction at genome-wide level in high resolution.
      This technology opens up the way to understand how local event mediated by
      protein-protein or protein-DNA interactions lead to the dynamic changes of
      overall chromosome structure and how variety of proteins make a regulatory
      network for the faithful execution of various chromosomal functions (i.e.,
      transcription, replication, recombination, repair, and partition). 

PMID- 24927834
TI  - Detecting protein-DNA interactions using a modified yeast one-hybrid system.
AB  - The yeast one-hybrid (Y1H) system has been among the methods of choice to detect
      protein-DNA interactions. However, conventional Y1H systems with a single
      auxotrophic reporter gene often suffer from high incidence of false positives to
      demonstrate a limited power in large-scale screenings. Here we describe a refined
      Y1H system that uses two independent bait sequences, each controlling a distinct
      reporter gene integrated in the host genome. With these modifications and a
      method of targeted DNA methylation, we succeeded in efficient isolation of clones
      for methylated DNA-binding proteins from mammalian cDNA libraries. 

PMID- 24927835
TI  - RNA sequencing: from sample preparation to analysis.
AB  - The introduction of RNA sequencing (RNA-seq), as a direct result of rapid
      progression of next-generation sequencing technologies, has revolutionized the
      world of transcriptomics. It enables quantification of the complete set of RNA
      with all its isoforms in a given cell, in far greater accuracy than before. Here,
      we provide a step-by-step guide to the sample preparation in RNA-seq and an
      overview of the bioinformatic analysis that is required following the cDNA
      sequencing. 

PMID- 24927836
TI  - Detecting expressed genes using CAGE.
AB  - Cap analysis of gene expression (CAGE) provides accurate high-throughput
      measurement of RNA expression. By the large-scale analysis of 5' end of
      transcripts using CAGE method, it enables not only determination of the
      transcription start site but also prediction of promoter region. Here we provide
      a protocol for the construction of no-amplification non-tagging CAGE libraries
      for Illumina next-generation sequencers (nAnT-iCAGE). We have excluded the
      commonly used PCR amplification and cleavage of restriction enzyme to eliminate
      any potential biases. As a result, we achieved less biased simple preparation
      process. 

PMID- 24927837
TI  - A tutorial to identify nonlinear associations in gene expression time series
      data.
AB  - The study of gene regulatory networks is the basis to understand the biological
      complexity of several diseases and/or cell states. It has become the core of
      research in the field of systems biology. Several mathematical methods have been
      developed in the last decade, especially in the analysis of time series gene
      expression data derived from microarrays and sequencing-based methods. Most of
      the models available in the literature assumes linear associations among genes
      and do not infer directionality in these connections or uses a priori biological
      knowledge to set the directionality. However, in several cases, a priori
      biological information is not available. In this context, we describe a
      statistical method, namely nonlinear vector autoregressive model to estimate
      nonlinear relationships and also to infer directionality at the edges of the
      network by using the temporal information of the time series gene expression data
      without a priori biological information. 

PMID- 24927838
TI  - Inference of TFRNs (2).
AB  - This chapter introduces to a study aiming at comprehensively understanding the
      transcription factor regulatory networks (TFRNs) that govern the process of a
      cell differentiation. Here we focus on the adipocyte differentiation. For the
      cell differentiation, we inferred its TFRN using the Bayesian network (BN)
      method. BNs have been widely used to estimate TFRNs. Many BN methods have been
      developed to estimate networks from TF expression data. However, BN-based methods
      require huge computational time to estimate large-scale networks. This chapter
      introduces to a BN-based deterministic method with reduced computational time.
      This approach generates all the combinational subnetworks of three TFs, estimates
      networks of the subnetworks by BN, and unites the networks into a single large
      network. This method decreases the search space of predicting TFRNs without
      degrading the solution accuracy compared with the greedy hill climbing (GHC)
      method. This chapter also presents a massively parallel implementation for the BN
      based inference of TFRNs. The system enables us to estimate large-scale (>10,000
      transcripts) multiple TFRNs from expression profiles of various tissues and
      conditions. The comparison among estimated TFRNs of adipose tissues with stimulus
      induction is conducted. The various regulations to Ucp1 (uncoupled protein 1) in
      those networks may reflect different responses of the tissues under the stimulus
      induction. 

PMID- 24927839
TI  - Identification of the minimal connected network of transcription factors by
      transcriptomic and genomic data integration.
AB  - Thanks to high-throughput experiments, biological conditions can be investigated
      at both the entire genomic and transcriptomic levels. In addition, protein
      protein interaction (PPI) data are widely available for well-studied organisms,
      such as human. In this chapter, we will present an integrative approach that
      makes use of these data to find the PPI module involving the key regulated
      transcription factors shared by a number of given conditions. These conditions
      could be for instance different cancer types. Briefly, for the studied
      conditions, we need to identify commonly affected chromosomal regions subjected
      to copy number alterations together with the identification of differentially
      expressed list of genes in each condition. Transcription factor activity will be
      inferred from these regulated gene lists. Then, we will define TFs, for which the
      activity could be explained by an associative effect of both loci copy number
      alteration and gene expression levels of their coding genes. PPI networks could
      be mined, afterwards, using appropriate algorithms to find the significant module
      that connect those TFs together. This module could be viewed as the minimal
      connected network of TFs, the regulation of which is shared between the
      investigated conditions. 

PMID- 24927840
TI  - Modeling and simulation using CellDesigner.
AB  - In silico modeling and simulation are effective means to understand how the
      regulatory systems function in life. In this chapter, we explain how to build a
      model and run the simulation using CellDesigner, adopting the standards such as
      SBML and SBGN. 

PMID- 24927841
TI  - Human genome network platform: a resource for TFRN analysis.
AB  - Genome Network Project (GNP) (Carninci et al., Science 309:1559-1563, 2005)
      Platform was developed as an integrated database, opening to the public the
      research findings within the GNP initiatives. Since the first release in 2006, it
      has gained a large amount of access from all over the world with public favor.
      The platform is unique and useful in that various types of experimental data for
      transcriptome analysis are intensively collected, organized, integrated, and
      visualized with major public datasets; and it can be freely accessed through a
      single interface with advanced search functionalities. This chapter describes the
      outline of GNP Platform, mainly elaborating on gene description model GNP
      Platform employed, major functionalities the platform provides, and a few
      examples of exploring the GNP Platform. 

PMID- 24927842
TI  - Identification of transcription factors activated in thymic epithelial cells
      during embryonic thymus development.
AB  - Differentiation of many immune-related cells is controlled by the expression
      levels and the activation status of transcription factors (TFs). We here describe
      a method to identify candidate TFs activated during the development of thymic
      epithelial cells (TECs) in the embryo. RNAs are isolated from fetal thymic organ
      cultures of wild-type and mutant mice and are subsequently analyzed by using a
      combination of comprehensive expression analysis and in silico data analysis in
      order to predict the TFs that might be activated. 

PMID- 24927843
TI  - Analysis of NFATc1-centered transcription factor regulatory networks in
      osteoclast formation.
AB  - Osteoclasts are bone-resorbing cells that differentiate from the
      macrophage/monocyte lineage. The master transcription factor NFATc1 has a central
      role in the process of this differentiation. Thus, it is important to understand
      the NFATc1-centered transcription factor regulatory networks (TFRNs) in terms of
      the mechanisms of NFATc1 expression and activation as well as the gene expression
      regulated by NFATc1. The Genome Network Project has provided a unique opportunity
      for the analysis of NFATc1-centered TFRNs in osteoclasts. Here we introduce a
      report on the application of the methods established by the project for
      osteoclast biology and a summarization of the results obtained in this project
      thus far. 

PMID- 24927844
TI  - Transcriptional regulation in adipogenesis through PPARgamma-dependent and 
      independent mechanisms by prostaglandins.
AB  - Adipogenesis is controlled by complex mechanisms, and transcription factors are
      involved in its regulation. PPARgamma is a ligand-dependent transcription factor
      and the most important one for adipogenesis. Although prostaglandin (PG) D2
      metabolites have been reported as being the ligands of PPARgamma, the endogenous
      PPARgamma ligand in adipocytes remains unclear. Here, we show the methods for the
      general analysis of adipocyte differentiation and the protocols for promoter
      analysis, fluorescence EMSA, and chromatin immunoprecipitation assay for the
      transcriptional regulation of the SREBP-1c-activated lipocalin-type PGD synthase
      gene in adipocytes. Moreover, we describe that PGD2 and its metabolites are
      involved in the regulation of adipogenesis through PPARgamma-dependent and 
      independent mechanisms. 

PMID- 24927845
TI  - Analysis of TFRNs associated with steroid hormone-related cancers.
AB  - Estrogen and androgen are important endocrine hormones that control physiological
      functions in reproductive organs and play roles in the generation and/or
      progression of steroid hormone-related cancers. Their cognate receptors function
      as hormone-dependent transcription factors, which directly regulate the
      expression of their target genes. Genome-wide analysis of hormone receptor
      related networks will provide new insights into the understanding of the
      molecular mechanism orchestrated by estrogen and androgen receptors, and will
      enable the development of new methods for the diagnosis and treatment of steroid
      hormone-related cancers. 

PMID- 24927846
TI  - Repositioning monocyte TFRN into fibroblasts.
AB  - Repositioning of cell-specific Transcription Factor Regulatory Networks (TFRNs)
      into another cell type is a pragmatic approach to elicit desired functions in
      impaired cells and also to investigate transcription regulations underlying
      cellular functions. However, a systematic method to identify a set of
      transcription factors (TFs) which can efficiently promote TFRN in a foreign cell
      type is lacking. Here, we demonstrate a perturbation-matrix method for the
      identification and repositioning of monocyte TFRNs in dermal fibroblasts. 

PMID- 24927847
TI  - An estimate of the cost of burnout on early retirement and reduction in clinical
      hours of practicing physicians in Canada.
AB  - BACKGROUND: Interest in the impact of burnout on physicians has been growing
      because of the possible burden this may have on health care systems. The
      objective of this study is to estimate the cost of burnout on early retirement
      and reduction in clinical hours of practicing physicians in Canada. METHODS:
      Using an economic model, the costs related to early retirement and reduction in
      clinical hours of physicians were compared for those who were experiencing
      burnout against a scenario in which they did not experience burnout. The January
      2012 Canadian Medical Association Masterfile was used to determine the number of
      practicing physicians. Transition probabilities were estimated using 2007-2008
      Canadian Physician Health Survey and 2007 National Physician Survey data.
      Adjustments were also applied to outcome estimates based on ratio of actual to
      planned retirement and reduction in clinical hours. RESULTS: The total cost of
      burnout for all physicians practicing in Canada is estimated to be $213.1 million
      ($185.2 million due to early retirement and $27.9 million due to reduced clinical
      hours). Family physicians accounted for 58.8% of the burnout costs, followed by
      surgeons for 24.6% and other specialists for 16.6%. CONCLUSION: The cost of
      burnout associated with early retirement and reduction in clinical hours is
      substantial and a significant proportion of practicing physicians experience
      symptoms of burnout. As health systems struggle with human resource shortages and
      expanding waiting times, this estimate sheds light on the extent to which the
      burden could be potentially decreased through prevention and promotion activities
      to address burnout among physicians.

PMID- 24927848
TI  - Imaging mimics of primary malignant tumors of the central nervous system (CNS).
AB  - Imaging has become a central part of the evaluation of lesions of the central
      nervous system. Despite patterns of the appearances of several types of central
      nervous system malignancies and improving resolution of imaging techniques, there
      are other processes that can display similar characteristics. Time and again,
      vascular, inflammatory, and vascular lesions will mimic a neoplastic process,
      requiring tissue diagnosis. With the introduction of advanced magnetic resonance
      imaging (MRI) and positron emission tomography (PET) imaging in the evaluation of
      the brain tumor, there has been improvement in determining whether a lesion is
      neoplastic, and further advances may lead to noninvasive pathological and
      molecular diagnoses. 

PMID- 24927849
TI  - The anti-lymphoma activities of anti-CD137 monoclonal antibodies are enhanced in
      FcgammaRIII(-/-) mice.
AB  - Agonistic monoclonal antibodies (mAbs) directed against the co-signaling molecule
      CD137 (4-1BB) elicit potent anti-tumor immunity in mice. This anti-tumor immunity
      has traditionally been thought to result from the ability of the Fab portion of
      anti-CD137 to function as an analog for CD137L. Although binding of CD137 by anti
      CD137 mAbs has the potential to cross-link the Fc fragments, enabling Fc
      engagement of low to moderate affinity Fc gamma receptors (FcgammaR), the
      relative import of such Fc-FcgammaR interactions in mediating anti-CD137
      associated anti-tumor immunity is unknown. We studied the ability of a rat anti
      mouse CD137 mAb (2A) to mediate the anti-tumor response against the EL4E7
      lymphoma in WT and FcgammaR(-/-) strains. 2A-treated FcRgamma(-/-) mice had
      improved anti-tumor immunity against EL4E7, which could be completely
      recapitulated in FcgammaRIII(-/-) animals. These improved anti-tumor responses
      were associated with increased splenic CD8beta T cell and dendritic cell (DC)
      populations. Furthermore, there was an increase in the number of DCs expressing
      high levels of the CD40, CD80, and CD86 molecules that are associated with more
      effective antigen presentation. Our results demonstrate an unexpected inhibitory
      role for FcgammaRIII in the anti-tumor function of anti-CD137 and underscore the
      need to consider antibody isotype when engineering therapeutic mAbs. 

PMID- 24927850
TI  - Prostate cancer outcomes in France: treatments, adverse effects and two-year
      mortality.
AB  - BACKGROUND: This very large population-based study investigated outcomes after a
      diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and
      adverse effects. METHODS: Among the 11 million men aged 40 years and over covered
      by the general national health insurance scheme, those with newly managed PCa in
      2009 were followed for two years based on data from the national health insurance
      information system (SNIIRAM). Patients were identified using hospitalisation
      diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects
      of PCa treatments were identified by using hospital diagnoses, specific
      procedures and drug refunds. RESULTS: The age-standardised two-year all-cause
      mortality rate among the 43,460 men included in the study was 8.4%, twice that of
      all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had
      undergone prostatectomy, 36% had been treated by hormone therapy, 29% by
      radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of
      treatment-related adverse effects varied according to age and type of treatment.
      Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were
      treated for erectile dysfunction and 24% were treated for urinary disorders. The
      frequency of treatment for these disorders decreased during the second year
      compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders:
      9% vs 20%). The frequencies of these treatments among men treated by external
      beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and
      69 years with treated PCa, 46% received treatments for erectile dysfunction and
      22% for urinary disorders. For controls without PCa but treated surgically for
      benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively.
      CONCLUSIONS: We report high survival rates two years after a diagnosis of PCa,
      but a high frequency of PCa treatment-related adverse effects. These frequencies
      remain underestimated, as they are based on treatments for erectile dysfunction
      and urinary disorders and do not reflect all functional outcomes. These results
      should help urologists and general practitioners to inform their patients about
      outcomes at the time of screening and diagnosis, and especially about potential
      treatment-related adverse effects.

PMID- 24927853
TI  - Effect of particle geometry on triple line motion of nano-fluid drops and deposit
      nano-structuring.
AB  - We illustrate the importance of particle geometry on droplet contact line
      pinning, 'coffee-stain' formation and nano-structuring within the resulting
      rings. We present the fundamentals of pure liquid droplet evaporation and then
      discuss the effect of particles on the evaporation process. The resulting coffee
      stain patterns and particle structuring within them are presented and discussed.
      In the second part, we turn our attention to the effect of particle geometry on
      the evaporation process. A wide range of particle shapes, categorised according
      to aspect ratio, from the simple shape of a sphere to the highly irregular shapes
      of platelets and tubes is discussed. Particle geometry effect on evaporation
      behaviour was quantified in terms of change in contact angle and contact radius
      for the stick-slip cases. Consequently the hysteretic energy barrier pinning the
      droplets was estimated, showing an increasing trend with particle aspect ratio.
      The three-phase contact line (TL) motion kinetics are complemented with analysis
      of the nano-structuring behaviour of each shape, leading to the identification of
      the two main parameters affecting nanoparticle self-assembly behaviour at the
      wedge. Flow velocity and wedge constraints were found to have antagonist effects
      on particle deposition, although these varied with particle shape. This
      description should help in understanding the drying behaviour of more complex
      fluids. Furthermore, knowing the fundamentals of this simple and inexpensive
      surface patterning technique should permit its tailoring to the needs of many
      potential applications. 

PMID- 24927851
TI  - Cost effectiveness of group follow-up after structured education for type 1
      diabetes: a cluster randomised controlled trial.
AB  - BACKGROUND: This study examines the cost effectiveness of group follow-up after
      participation in the Dose Adjustment for Normal Eating (DAFNE) structured
      education programme for type 1 diabetes. METHODS: Economic evaluation conducted
      alongside a cluster randomised controlled trial involving 437 adults with type 1
      diabetes in Ireland. Group follow-up involved two group education 'booster'
      sessions post-DAFNE. Individual follow-up involved two standard one-to-one
      hospital clinic visits. Incremental costs, quality-adjusted life years (QALYs)
      gained and cost effectiveness were estimated at 18 months. Uncertainty was
      explored using sensitivity analysis and by estimating cost effectiveness
      acceptability curves. RESULTS: Group follow-up was associated with a mean
      reduction in QALYs gained of 0.04 per patient (P value, 0.052; 95% CI, -0.08 to
      0.01, intra-class correlation (ICC), 0.033) and a mean reduction in total
      healthcare costs of ?772 (P value, 0.020; 95% CI, -1,415 to -128: ICC, 0.016) per
      patient. At alternative threshold values of ?5,000, ?15,000, ?25,000, ?35,000,
      and ?45,000, the probability of group follow-up being cost effective was
      estimated to be 1.000, 0.762, 0.204, 0.078, and 0.033 respectively. CONCLUSIONS:
      The results do not support implementation of group follow-up as the sole means of
      follow-up post-DAFNE. Given the reported cost savings, future studies should
      explore the cost effectiveness of alternative models of group care for diabetes.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN79759174 (assigned: 9
      February 2007).

PMID- 24927852
TI  - Effective suppression of dengue virus using a novel group-I intron that induces
      apoptotic cell death upon infection through conditional expression of the Bax C
      terminal domain.
AB  - INTRODUCTION: Approximately 100 million confirmed infections and 20,000 deaths
      are caused by Dengue virus (DENV) outbreaks annually. Global warming and rapid
      dispersal have resulted in DENV epidemics in formally non-endemic regions.
      Currently no consistently effective preventive measures for DENV exist, prompting
      development of transgenic and paratransgenic vector control approaches.
      Production of transgenic mosquitoes refractory for virus infection and/or
      transmission is contingent upon defining antiviral genes that have low
      probability for allowing escape mutations, and are equally effective against
      multiple serotypes. Previously we demonstrated the effectiveness of an anti-viral
      group I intron targeting U143 of the DENV genome in mediating trans-splicing and
      expression of a marker gene with the capsid coding domain. In this report we
      examine the effectiveness of coupling expression of DeltaN Bax to trans-splicing
      U143 intron activity as a means of suppressing DENV infection of mosquito cells.
      RESULTS: Targeting the conserved DENV circularization sequence (CS) by U143
      intron trans-splicing activity appends a 3' exon RNA encoding DeltaN Bax to the
      capsid coding region of the genomic RNA, resulting in a chimeric protein that
      induces premature cell death upon infection. TCID50-IFA analyses demonstrate an
      enhancement of DENV suppression for all DENV serotypes tested over the identical
      group I intron coupled with the non-apoptotic inducing firefly luciferase as the
      3' exon. These cumulative results confirm the increased effectiveness of this
      alphaDENV-U143-DeltaN Bax group I intron as a sequence specific antiviral that
      should be useful for suppression of DENV in transgenic mosquitoes. Annexin V
      staining, caspase 3 assays, and DNA ladder observations confirm DCA-DeltaN Bax
      fusion protein expression induces apoptotic cell death. CONCLUSION: This report
      confirms the relative effectiveness of an anti-DENV group I intron coupled to an
      apoptosis-inducing DeltaN Bax 3' exon that trans-splices conserved sequences of
      the 5' CS region of all DENV serotypes and induces apoptotic cell death upon
      infection. Our results confirm coupling the targeted ribozyme capabilities of the
      group I intron with the generation of an apoptosis-inducing transcript increases
      the effectiveness of infection suppression, improving the prospects of this
      unique approach as a means of inducing transgenic refractoriness in mosquitoes
      for all serotypes of this important disease.

PMID- 24927854
TI  - [Two cases of sinus histiocytosis with massive cervical lymphadenopathy
      (Destombes-Rosai-Dorfman disease)].
AB  - INTRODUCTION: Sinus histiocytosis with massive lymphadenopathy is a rare disease.
      Its location is ubiquitous, but the most frequent is cervical lymph nodes.
      OBSERVATION: We report 2 cases of sinus histiocytosis with massive
      lymphadenopathy. The patients were respectively 9 and 30 years of age. They both
      presented with bilateral cervical polylymphadenopathy with a cervical compression
      syndrome in the first patient. The diagnosis was made histologically by
      demonstrating histiocyte emperipolesis, in the first case, and by immuno
      histochemistry in the second. The treatment was corticosteroids, resulting in an
      almost total involution. DISCUSSION: Sinus histiocytosis with massive
      lymphadenopathy is a clinical and a specific pathology, but its etiopathogenesis
      remains to be elucidated. The cervical localization is common. The definitive
      diagnosis is histological. There is currently no codified treatment. The outcome
      is usually favorable, apart from mechanical and systemic complications that are
      important prognostic factors.

PMID- 24927855
TI  - First direct comparison of clinical outcomes between European and Asian cohorts
      in transcatheter aortic valve implantation: the Massy study group vs. the PREVAIL
      JAPAN trial.
AB  - BACKGROUND: The efficacy and safety of transcatheter aortic valve implantation
      (TAVI) in Asian populations were unknown. The purpose of this study was to
      compare directly the clinical outcomes of the first Japanese trial and a European
      single-center experience after TAVI. METHODS AND RESULTS: Between April 2010 and
      October 2011, 64 patients were included in the PREVAIL JAPAN multicenter trial
      which was set up to evaluate the safety and efficacy of the Edwards SAPIEN XTTM
      (Edwards Lifesciences, Irvine, CA, USA) in high-risk Japanese patients with
      severe aortic stenosis. Between March 2010 and January 2012, 237 consecutive
      patients treated with TAVI using the Edwards SAPIEN XTTM prosthesis at Institut
      Cardiovasculaire Paris Sud were prospectively included in the Massy cohort. We
      compared the clinical outcomes of these two cohorts. Patients were of similar age
      (83.4+/-6.6 years vs. 84.5+/-6.1 years, p=0.25), but logistic EuroSCORE was
      higher in the Massy cohort (20.2+/-11.7% vs. 15.6+/-8.0%, p<0.01). Body surface
      area was smaller in the PREVAIL JAPAN cohort (1.41+/-0.14m(2) vs. 1.72+/
      0.18m(2); p<0.01) as was the annulus diameter (20.4+/-1.46mm vs. 22.0+/-1.84mm,
      p<0.01). The transfemoral approach was used in 57.8% in the Japanese cohort vs.
      51.5% in the Massy cohort. Device success was similar (89.1% vs. 94.1%, p=0.21,
      respectively), as well as 30-day and 6-month survival rates (92.2% vs. 90.7% and
      89.1% vs. 83.1%, p=0.71 and p=0.25, respectively). The incidence of major
      vascular complications was not significantly different between the two groups
      (9.4% vs. 5.9%, p=0.23, respectively). A higher post-procedural mean pressure
      gradient was observed in the PREVAIL JAPAN cohort (12.7+/-11.4mmHg vs. 10.1+/
      3.6mmHg, p=0.01), but satisfactory improvement in 6-month functional status was
      obtained in both cohorts (76.5% vs. 77.2%, p=0.91). CONCLUSIONS: Clinical
      outcomes after TAVI in the patients included in the PREVAIL JAPAN trial were
      acceptable and as safe as that of a single-center European cohort.

PMID- 24927856
TI  - Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIRTM
      therapeutic protein, in combination with rituximab and bendamustine in relapsed
      indolent lymphoma patients.
AB  - PURPOSE: CD37 is cell surface tetraspanin present on normal and malignant B
      cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic
      that triggers direct caspase independent apoptosis of malignant B cells and
      induces antibody-dependent cell-mediated cytotoxicity. This study evaluated the
      safety, pharmacokinetics, and efficacy of otlertuzumab administered in
      combination with rituximab and bendamustine to patients with relapsed, indolent B
      cell non-Hodgkin Lymphoma (NHL). METHODS: Patients with relapsed or refractory
      NHL received otlertuzumab (10 or 20 mg/kg) intravenously (IV) on days 1 and 15,
      bendamustine (90 mg/m(2)) on days 1 and 2, and rituximab (375 mg/m(2)) on day 1
      for up to six 28 day cycles. Responses were determined using standard criteria.
      RESULTS: Twelve patients were treated with 6 patients at each dose level; median
      age was 57 years (range, 51-79), and median number of prior regimens was 3
      (range, 1-4). All patients had relapsed after prior rituximab including 7
      refractory to their most recent previous treatment. In the 10 and 20 mg/kg dose
      cohorts, the mean half-life was 8 and 10 days following the first dose, and 12 or
      14 days following 12 doses of otlertuzumab, respectively. Overall response rate
      was 83% (10/12) with 4 CRs (32%). The most frequent adverse events were
      neutropenia, nausea, fatigue, leukopenia, and insomnia; most were grade 1 or 2.
      CONCLUSIONS: Otlertuzumab in combination with rituximab and bendamustine was well
      tolerated and induced responses in the majority of patients with relapsed
      indolent B-NHL. NCI Clinical Trials Network registration: NCT01317901.

PMID- 24927858
TI  - Esterase mediated resistance against synthetic pyrethroids in field populations
      of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in Punjab districts of
      India.
AB  - Detection of resistance levels against cypermethrin and deltamethrin, the most
      commonly used synthetic pyrethroids (SP), in Rhipicephalus (Boophilus) microplus
      collected from thirteen districts of Punjab (India) was carried out using adult
      immersion test. The regression graphs of probit mortality of ticks plotted
      against log values of concentrations of drugs were utilized for the determination
      of slope of mortality, lethal concentration for 50% (LC50), 95% (LC95) and
      resistance factor (RF). On the basis of the data generated on variables
      (mortality, egg mass weight, reproductive index and percentage inhibition of
      oviposition) the resistance levels were categorized. Against cypermethrin RFs of
      1.48-11.22 were recorded in 12 isolates whereas, one isolate was susceptible.
      Resistance factors against deltamethrin were 2.4-38.54 and all 13 isolates were
      found to be resistant. Quantitative analysis of general esterase activity
      (measured by the production of the metabolite naphthol) revealed a range of 3.34
      +/- 0.30-13.75 +/- 1.33 and 1.31 +/- 0.15-8.09 +/- 0.68 MUmol/min/mg protein for
      alpha and beta-esterase activity, respectively in different field isolates.
      Further, multiple pairwise comparisons of the mean values with susceptible strain
      (Tukey, P = 0.05) revealed significant elevated levels of both alpha-esterase and
      beta-esterase in nine tick isolates resistant to both deltamethrin and
      cypermethrin. The data generated on acaricide resistant status and esterase
      mediated mechanism in ticks will help in formulating tick control strategy for
      the region.

PMID- 24927857
TI  - Novel antitumour indole alkaloid, Jerantinine A, evokes potent G2/M cell cycle
      arrest targeting microtubules.
AB  - Natural products play a pivotal role in the treatment of cancer; identification
      of compounds such as taxanes and the vinca alkaloids were seminal landmarks in
      natural product drug discovery. Jerantinine A, a novel Aspidosperma alkaloid
      isolated from plant species Tabernaemontana corymbosa, was previously reported to
      possess cytotoxic activity against vincristine-resistant nasopharyngeal carcinoma
      cells and is therefore an ideal candidate for biological investigation.
      Furthermore, Tabernaemontana corymbosa, has been placed in the endangered list of
      threatened species by the International Union for Conservation of Nature thus
      making it a priority to elucidate the biological activity of this alkaloid.
      Herein, we report detailed biological evaluation of jerantinine A on various
      human-derived carcinoma cell lines. Our preliminary screens showed that
      significant inhibition of cell growth and colony formation accompanied time- and
      dose-dependent induction of apoptosis in human cancer cell lines after treatment
      with jerantinine A. Dose-dependent accumulations of cleaved PARP and caspase 3
      further confirmed apoptosis. Profound G2/M cell cycle arrest was observed 24 h
      after treatment in all cell lines. Characteristics of mitotic arrest including
      inhibition of tubulin polymerisation, microtubule disruption, aneuploidy, and
      cyclin B1 down-regulation were clearly observed. The potent anti-proliferative,
      pro-apoptotic, and tubulin-destabilising activities of jerantinine A warrant
      further development of this molecule as a potential chemotherapeutic agent.

PMID- 24927859
TI  - Defect reconstruction over the olecranon with the distally extended lateral arm
      flap.
AB  - Defect reconstruction over the olecranon should be reliable, quick, relatively
      simple and with minimal complications. More recently, perforator flaps have been
      described with the benefit of minimal donor site morbidity when compared with
      muscle flaps or flaps relying on the major arteries of the upper extremity. So
      far, most of these flaps were harvested on the upper arm and rotated 180 degrees 
      into the defect. The aim of the present study was to analyse the results with the
      proximally based, distally extended lateral arm flap for soft-tissue
      reconstruction over the olecranon. The subcutaneous tissue layer in this area is
      thinner than in the upper arm, and less rotation of the pedicle is necessary. The
      location of the perforator just proximal to the lateral epicondyle and the
      precise territory of the flap are well known. Nine consecutive male patients with
      a mean age of 57+/-27 years presenting with soft-tissue defects after surgical
      treatment of bursitis (eight cases) or a pressure sore (one case) were operated
      on. The mean operation time was 60+/-15 min. In eight of the nine cases, the flap
      healed uneventfully or with a minor complication (fistula). One patient underwent
      revision surgery due to marginal flap necrosis. The defect was closed with a
      local advancement flap. In conclusion, the flap was reliable, relatively simple
      and quick to harvest, and yielded acceptable aesthetic results with minimal
      bulging over the olecranon. Postoperative recovery was relatively painless and
      short.

PMID- 24927860
TI  - The use of computed tomography for the estimation of DIEP flap weights in breast
      reconstruction: a simple mathematical formula.
AB  - BACKGROUND: Estimation of the volume of abdominal tissue is desirable when
      planning autologous abdominal based breast reconstruction. However, this can be
      difficult clinically. The aim of this study was to develop a simple, yet reliable
      method of calculating the deep inferior epigastric artery perforator flap weight
      using the routine preoperative computed tomography angiogram (CTA) scan. METHODS:
      Our mathematical formula is based on the shape of a DIEP flap resembling that of
      an isosceles triangular prism. Thus its volume can be calculated with a standard
      mathematical formula. Using bony landmarks three measurements were acquired from
      the CTA scan to calculate the flap weight. This was then compared to the actual
      flap weight harvested in both a retrospective feasibility and prospective study.
      RESULTS: In the retrospective group 17 DIEP flaps in 17 patients were analyzed.
      Average predicted flap weight was 667 g (range 293-1254). The average actual flap
      weight was 657 g (range 300-1290) giving an average percentage error of 6.8% (p
      value for weight difference 0.53). In the prospective group 15 DIEP flaps in 15
      patients were analyzed. Average predicted flap weight was 618 g (range 320-925).
      The average actual flap weight was 624 g (range 356-970) giving an average
      percentage error of 6.38% (p-value for weight difference 0.57). CONCLUSIONS: This
      formula is a quick, reliable and accurate way of estimating the volume of
      abdominal tissue using the preoperative CTA scan.

PMID- 24927861
TI  - Lymphatic drainage patterns from primary cutaneous tumours of the forehead:
      refining the recommendations for selective neck dissection.
AB  - BACKGROUND: Recommended selective neck dissections for primary cutaneous tumours
      on the head and neck are based largely on clinical recurrence data acquired prior
      to the era of lymphatic mapping and sentinel lymph node (SLN) biopsy. This study
      aimed to examine lymphatic drainage patterns from the forehead in order to
      provide evidence upon which to base recommendations regarding the extent of neck
      dissection. METHODS: Data were collected prospectively from all patients
      undergoing lymphoscintigraphy following diagnosis of a primary cutaneous tumour
      on the forehead. The site of injection of radioisotope was documented using a co
      ordinate-based mapping system. The forehead was divided into glabellar, supra
      orbital and anterior temple zones. The location of all SLNs was recorded and
      drainage patterns were analysed. RESULTS: Between 1994 and 2006, 152 patients
      underwent lymphoscintigraphy for primary cutaneous tumours on the forehead.
      Drainage was to 3.0 SLNs in 2.1 lymph node fields (mean values). Drainage was to
      ipsilateral SLNs in 85% of cases. Between zones there were significant
      differences in drainage patterns and the frequency of bilateral drainage. From
      the glabellar zone, drainage was more frequently to a higher number of SLNs and
      SLN fields, and to level I nodes. CONCLUSIONS: The forehead can be divided into
      zones with patterns of lymphatic drainage that vary significantly in terms of
      number of SLNs, number of SLN sites, likelihood of drainage to contralateral SLNs
      and predictability of drainage pattern. Drainage to level 1 nodes from the
      anterior temple is rare, suggesting that it may be safe to exclude this level
      when performing a selective neck dissection for tumours in this zone.

PMID- 24927862
TI  - Correction of the hypertrophic conchal bowl without cartilage excision.
AB  - We present our technique for conchal bowl reduction. The procedure is fast, easy
      to learn and reproducible. The technique has now been used in a consecutive
      series of 208 ears. We describe the steps taken and the outcomes. The main aims
      of this procedure were; the preservation of conchal bowl width and avoidance of
      cartilage excision. This cartilage can then be used for grafting if a rhinoplasty
      is considered in the future. 

PMID- 24927863
TI  - Immediate breast reconstruction with acellular dermal matrix: factors affecting
      outcome.
AB  - BACKGROUND: The use of acellular dermal matrix (ADM) for coverage of the lower
      pole in immediate implant-based breast reconstruction has changed surgeons'
      practice. We present our experience using a porcine ADM (Strattice), focusing on
      short-term outcomes, patient selection, and technique adaptations that may
      influence outcome. METHODS: A two-center, retrospective, cohort study was
      performed from December 2008 to October 2012 at Guy's and St. Thomas' Hospitals,
      London, and Clinic Pyramide, Zurich. The study period was divided into two
      periods: Period 1 which spanned from December 2008 to October 2010 and Period 2
      from January 2011 to October 2012 wherein technique adaptations were introduced.
      Short-term complications after reconstructive surgery were compared between
      Periods 1 and 2. RESULTS: A total of 149 patients underwent 200 reconstructions
      (110 one-stage and 90 two-stage) following oncologic (134 breasts) or
      prophylactic (66 breasts) mastectomy. The mean follow-up was 22.2 months. The
      total complication rate was 32.5%, including infection, 11.5%; hematoma, 5%;
      seroma, 10.5%; skin necrosis, 3.5%; and serious wound breakdowns with implant
      exposure, 1.5%. Complications resulted in 3% requiring an early exchange of
      implant/expander and in 12.5% requiring explantation. A significant reduction in
      total complications, infection, implant exposure, and implant loss were noted in
      Period 2. Multivariate analysis showed time period of surgery (Period 1), single
      stage reconstruction, and patient characteristics (mastectomy weight>600 g, or
      body mass index (BMI)>30, or smoking) to be statistically significant risk
      factors for the development of postoperative complications. Neoadjuvant
      chemotherapy showed a trend towards higher complication rates. CONCLUSION: The
      high rate of early complications in this study was mostly related to patient
      characteristics and learning curves and highlights the importance of patient
      selection and technique principles in optimizing the outcome.

PMID- 24927864
TI  - Vacuum-assisted lipectomy technique for optimized skin flap defatting.

PMID- 24927865
TI  - The primary excision of benign dermal cylindroma on the scalp in the correct
      layer is crucial to avoid recurrence with cranial bone erosion.

PMID- 24927866
TI  - Cement in cement revision of the femoral component using a collarless triple
      taper: a midterm clinical and radiographic assessment.
AB  - This study describes the midterm clinical and radiological results of the cement
      in cement technique for the femur using a collarless triple taper. Radiographic
      assessment was made retrospectively from 44 patients at two time points. Clinical
      outcomes included the Oxford Hip Score, EQ5D and Self Reported Patient
      Satisfaction Scale. Implant and patient survival were also recorded. The mean
      clinical follow up period was 5years 3months and the radiological follow up
      2years 10months. The mean OHS was 34, the mean EQ5D 0.814 and the mean SAPS 94.
      Kaplan-Meier survival with revision, as the end point was 95.2% at 11years with a
      survivorship of 76.5% with death as the end point. Cement in cement revision
      using a collarless triple tapered stem demonstrates promising results both
      clinically and radiologically at midterm follow up.

PMID- 24927867
TI  - High failure rates of the Spectron EF stem at a minimum of 10 year's follow-up.
AB  - We prospectively followed 112 hips, undergoing THA with a Spectron EF stem. At
      mean follow-up of 11.2years, 21 patients had died. We obtained radiological
      follow-up in 99% and clinical follow-up in 100% of the surviving 91 hips. Fifty
      four percent demonstrated osteolysis in at least one Gruen zone. Twenty-two hips
      required revision for all causes, with a further five stems radiologically loose.
      With endpoint being stem revision for aseptic loosening or radiological failure,
      survivorship at 11years was 0.783. We believe the addition of a rougher surface
      finish has contributed to the high levels of osteolysis and stem failure seen
      with the Spectron EF.

PMID- 24927868
TI  - Risk factors for manipulation after total knee arthroplasty: a pooled electronic
      health record database study.
AB  - A commercially available software platform, Explorys (Explorys, Inc., Cleveland,
      OH), was used to mine a pooled electronic healthcare database consisting of the
      medical records of more than 27 million patients. A total of 229,420 patients had
      undergone a total knee arthroplasty; 3470 (1.51%) patients were identified to
      have undergone manipulation under anesthesia. Individual risk factors of being
      female, African American race, age less than 60, BMI >30 and nicotine dependence
      were determined to have relative risk of 1.25, 2.20, 3.46, 1.33 and 1.32
      respectively. Depressive disorder, diabetes mellitus, opioid abuse/dependence and
      rheumatoid arthritis were not significant risk factors. African Americans under
      the age of 60 at time of TKA had the greatest incidence of MUA (5.17%) and
      relative risk of 3.73 (CI: 3.36, 4.13).

PMID- 24927869
TI  - Comparison of health care costs between aseptic and two stage septic hip
      revision.
AB  - The number of septic and aseptic total hip arthroplasty (THA) revisions will
      increase, which involves a greater financial burden. We here provide a
      retrospective consecutive analysis of the major variable direct costs involved in
      revision THA for aseptic and septic failure. A total of 144 patients (30 septic,
      114 aseptic) treated between January 1, 2009 and March 31, 2012 was included. The
      management of septic THA loosening is much more expensive than that of aseptic
      loosening ($14,379.8 vs. $5,487.4). This difference is mainly attributable to the
      two-stage exchange technique used for septic failure (hospital stay: 40.2 vs.
      15.6 days) and significantly higher implant costs ($3,930.9 vs. $2,298.2). The
      septic implantation part is on average $3,384.6 more expensive than aseptic
      procedures (P < .001). 

PMID- 24927870
TI  - First Evidence of Comorbidity of Problem Gambling and Other Psychiatric Problems
      in a Representative Urban Sample of South Africa.
AB  - We investigate the extent to which problem gambling in a recent South African
      sample, as measured by the Problem Gambling Severity Index (PGSI), is comorbid
      with depression, anxiety and substance abuse. Data are from the 2010 South
      African National Urban Prevalence Study of Gambling Behavior. A representative
      sample of the urban adult population in South Africa (N = 3,000). Responses to
      the 9-item PGSI and ratings on the Beck Depression Index, the Beck Anxiety
      Inventory, and the World Health Organization Alcohol, Smoking and Substance
      Involvement Screening Tool (WHO ASSIST). Cross tabulations and Chi square
      analyses along with logistic regression analyses with and without controls for
      socio-demographic and/or socio-economic variables were used to identify
      comorbidities. The prevalence of depression, anxiety, alcohol and substance use
      were clearly higher among the sample at risk for problem gambling. Black African
      racial status and living in areas characterized by migrant mining workers was
      associated with increased risk of problem gambling and comorbidities. There is
      strong evidence that findings of comorbidities between pathological gambling and
      depression, anxiety and substance abuse in developed countries generalize to the
      developing country of South Africa. Historical context, however, gives those
      comorbidities a unique demographic distribution.

PMID- 24927871
TI  - Dendritic cells transduced with CPEB4 induced antitumor immune response.
AB  - Much evidence leads to the exploration of immunologic approaches for eliminating
      tumor cells. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is
      considered to be a novel therapeutical target for glioblastoma. In this study, we
      transduced DCs with CPEB4 to explore the immune response in vivo. We found that
      DCs transduced with recombinant adenovirus encoding CPEB4 could induce specific
      cytotoxic T lymphocytes (CTLs) to lyse glioma cells and augment the number of IFN
      gamma secreting T-cells in mice. In addition, the modified DCs could effectively
      protect mice from lethal challenges against glioma cells, reduce tumor growth and
      increase the mice life span. These results suggest that the DC transduced with
      CPEB4 may induce anti-tumor immunity against glioma cells and might be used as an
      efficient tumor vaccine in clinical applications. 

PMID- 24927872
TI  - Automated processing of fluorescence in-situ hybridization slides for HER2
      testing in breast and gastro-esophageal carcinomas.
AB  - BACKGROUND: HER2 fluorescence in-situ hybridization (FISH) is used in breast and
      gastro-esophageal carcinoma for determining HER2 gene amplification and patients'
      eligibility for HER2 targeted therapeutics. Traditional manual processing of the
      FISH slides is labor intensive because of multiple steps that require hands on
      manipulation of the slides and specifically timed intervals between steps. This
      highly manual processing also introduces inter-run and inter-operator variability
      that may affect the quality of the FISH result. Therefore, we sought to
      incorporate an automated processing instrument into our FISH workflow. METHODS:
      Twenty-six cases including breast (20) and gastro-esophageal (6) cancer
      comprising 23 biopsies and three excision specimens were tested for HER2 FISH
      (Pathvysion, Abbott) using the Thermobrite Elite (TBE) system (Leica). Up to 12
      slides can be run simultaneously. All cases were previously tested by the
      Pathvysion HER2 FISH assay with manual preparation. Twenty cells were counted by
      two observers for each case; five cases were tested on three separate runs by
      different operators to evaluate the precision and inter-operator variability.
      RESULTS: There was 100% concordance in the scoring between the manual and TBE
      methods as well as among the five cases that were tested on three runs. Only one
      case failed due to poor probe hybridization. In total, seven cases were positive
      for HER2 amplification (HER2:CEP17 ratio >2.2) and the remaining 19 were negative
      (HER2:CEP17 ratio <1.8) utilizing the 2007 ASCO/CAP scoring criteria. Due to the
      automated denaturation and hybridization, for each run, there was a reduction in
      labor of 3.5h which could then be dedicated to other lab functions. CONCLUSION:
      The TBE is a walk away pre- and post-hybridization system that automates FISH
      slide processing, improves work flow and consistency and saves approximately 3.5h
      of technologist time. The instrument has a small footprint thus occupying minimal
      counter space. TBE processed slides performed exceptionally well in comparison to
      the manual technique with no disagreement in HER2 amplification status.

PMID- 24927873
TI  - Complex/variant translocations in chronic myelogenous leukemia (CML): genesis and
      prognosis with 4 new cases.
AB  - In 5-10% of cases with CML, variant or complex translocations (CT) are seen that
      may result in atypical fluorescence in situ hybridization signal patterns. Dual
      color, dual fusion fluorescence in situ hybridization (D-FISH) patterns are
      instrumental in identifying the genesis of these CT, but their prognostic
      implications remain controversial. The most common mechanism is a two-step
      process in which a standard two-way translocation (9;22) is followed by
      subsequent rearrangements involving other chromosomes. The second common
      mechanism is the one-step process wherein breakage occurs simultaneously on
      different chromosomes leading to CT. The typical D-FISH pattern seen with the one
      step mechanism is 1F2G2R, while the pattern for the two-step mechanism can be
      variable (2F1G1R, 1F1G1R, 1F1G2R, 1F2G1R, etc.). We have studied 4 cases of CT
      using metaphase FISH with triple color, dual fusion ASS1, ABL1 and BCR probes to
      understand the genesis of these CT. All the patients were treated with imatinib,
      but only patients 3 and 4 showed remission. Our results indicate that the CT in
      cases 1, 3 and 4 arose from a one-step mechanism and case 2 from a multi-step
      mechanism. Response to imatinib varied from full remission to no response. Long
      term follow-up is necessary to evaluate the prognostic implications of these CT. 

PMID- 24927874
TI  - JK1 (FAM134B) represses cell migration in colon cancer: a functional study of a
      novel gene.
AB  - BACKGROUND: JK1 is a novel cancer-related gene with unknown functional role in
      carcinogenesis. The aim of this study is to investigate the role of JK1 gene in
      carcinogenesis in an in vitro cell proliferation and migration analysis model.
      METHODS: Small hairpin RNAs (shRNA) were designed to knock-down JK1 expression in
      colon cancer cell line (SW480) using transduction ready lentiviral particles.
      Cell proliferation and cell migration assays were performed on multiple
      extracellular matrices to investigate the cellular effects of JK1 in colon cancer
      cells. A non-cancer colonic epithelial cell line (FHC) was used to compare the
      expression of JK1 in cancer cell line. RESULTS: JK1 knock-down did not affect
      cellular proliferation or survival in colon cancer. However, the manipulation
      increased cancer cell migration rates on collagen and fibronectin substrates.
      CONCLUSIONS: JK1 was shown for the first time to have a functional role in the
      pathogenesis of colon cancer. The results imply that JK1 represses the capacity
      of cancer cells to migrate within their tissue. They also concurred with the
      previous findings of JK1 activity correlations with clinical and pathological
      features in colon cancer. The capacity may have utility as a means to prevent
      cancer cells forming metastases.

PMID- 24927875
TI  - Advances in treating amyotrophic lateral sclerosis: insights from
      pathophysiological studies.
AB  - Amyotrophic lateral sclerosis (ALS) is the most frequently occurring of the
      neuromuscular degenerative disorders, with a median survival time of 3-5 years.
      The pathophysiological mechanisms underlying ALS are multifactorial, with a
      complex interaction between genetic factors and molecular pathways. To date 16
      genes and loci have been associated with ALS, with mutations in DNA/RNA
      regulating genes including the recently described c9orf72 (chromosome 9 open
      reading frame 72) gene, suggesting an important role for dysregulation of RNA
      metabolism in ALS pathogenesis. Further, dysfunction of molecular pathways,
      including glutamate-mediated excitotoxicity, has been identified in sporadic and
      familial ALS, indicating the existence of a common pathogenic pathway. These
      pathophysiological insights have suggested novel therapeutic approaches,
      including stem cell and genetics-based strategies, providing hope for feasible
      treatment of ALS. 

PMID- 24927877
TI  - Assembling more O2 uptake responses: is it possible to merely stack the repeated
      transitions?
AB  - Kinetic parameters for pulmonary O2 uptake at exercise onset are estimated by non
      linear regression on repeated responses assembled together. The native data
      contain the information, thus the "stacking" of the responses should provide
      correct values and uncertainties. Kinetic parameters and corresponding
      uncertainties (computed from the asymptotic standard errors; ASE) were estimated
      on 10(4) simulated noisy responses (with time constant tau=25s), repeated 10
      times and assembled over an increasing number of repetitions (Nr) by "stacking"
      or ensemble averaging the responses processed to obtain 1s bins ("1-s-bins").
      Independent of the assembling method, the average estimated tau amounted to
      ~25.05 s. Independent of Nr, the "1-s-bins" and the "stacking" yielded an ASE/SD
      ratio for tau amounting to ~0.52 and ~0.98, respectively, resulting in a
      probability of including tau=25s within the estimated uncertainty from an
      individual kinetics amounting to ~70% and >94% for the "1-s-bins" and the
      "stacking", respectively. In conclusion, the "stacking" allowed obtaining, also
      for individual kinetics, coherent estimated parameters and associated
      uncertainties.

PMID- 24927876
TI  - Elevated expression levels of miR-143/5 in saphenous vein smooth muscle cells
      from patients with Type 2 diabetes drive persistent changes in phenotype and
      function.
AB  - Type 2 diabetes (T2DM) promotes premature atherosclerosis and inferior prognosis
      after arterial reconstruction. Vascular smooth muscle cells (SMC) respond to
      patho/physiological stimuli, switching between quiescent contractile and
      activated synthetic phenotypes under the control of microRNAs (miRs) that
      regulate multiple genes critical to SMC plasticity. The importance of miRs to SMC
      function specifically in T2DM is unknown. This study was performed to evaluate
      phenotype and function in SMC cultured from non-diabetic and T2DM patients, to
      explore any aberrancies and investigate underlying mechanisms. Saphenous vein SMC
      cultured from T2DM patients (T2DM-SMC) exhibited increased spread cell area,
      disorganised cytoskeleton and impaired proliferation relative to cells from non
      diabetic patients (ND-SMC), accompanied by a persistent, selective up-regulation
      of miR-143 and miR-145. Transfection of premiR-143/145 into ND-SMC induced
      morphological and functional characteristics similar to native T2DM-SMC;
      modulating miR-143/145 targets Kruppel-like factor 4, alpha smooth muscle actin
      and myosin VI. Conversely, transfection of antimiR-143/145 into T2DM-SMC
      conferred characteristics of the ND phenotype. Exposure of ND-SMC to transforming
      growth factor beta (TGFbeta) induced a diabetes-like phenotype; elevated miR
      143/145, increased cell area and reduced proliferation. Furthermore, these
      effects were dependent on miR-143/145. In conclusion, aberrant expression of miR
      143/145 induces a distinct saphenous vein SMC phenotype that may contribute to
      vascular complications in patients with T2DM, and is potentially amenable to
      therapeutic manipulation. 

PMID- 24927878
TI  - Racial and ethnic diversity in studies of late-life mental health.

PMID- 24927879
TI  - Fear of aging moderates post-traumatic stress disorder symptoms among older
      adults exposed to Hurricane Sandy.

PMID- 24927880
TI  - Genomic characterization and expression pattern of Bf/C2 and C4 in miiuy croaker
      and molecular evolution analysis on mammals and fishes.
AB  - The complement system plays an important role in both innate and adaptive host
      defense against the invading microorganisms in vertebrates. It can be activated
      by three pathways: the classical, alternative and lectin pathways. Bf/C2 and C4,
      as members of complement, play a pivotal role in the activation of the complement
      system. In our study, we identified Bf/C2 and C4 genes and genomic structure in
      miiuy croaker, and expression patterns of Bf/C2 and C4 genes was analyzed. In
      healthy miiuy croaker tissues, Bf/C2 and C4 genes were found to be ubiquitously
      expressed in all ten tested tissues. Analysis of expression of Bf/C2 and C4 genes
      after bacterial infection showed a significant up-regulated in liver. The
      evolutionary analysis showed that the ancestral lineages of Bf/C2 and C4 genes in
      mammals and fishes experienced positive selection indicated that the ancestors of
      mammals and fishes had further evolved to adapt to their environment,
      respectively. A series of maximum likelihood (ML) methods were used to study the
      evolution on vertebrates' Bf/C2 and C4 genes. One and five positive selection
      sites were found in mammals of Bf/C2 and C4 genes, but no positive selection site
      was found in fishes of Bf/C2 and C4 genes, indicating that Bf/C2 and C4 genes in
      mammals and fishes underwent different evolutionary patterns.

PMID- 24927881
TI  - Stability of severely stiff elbows after complete open release: treatment by
      ligament repair with suture anchors and hinged external fixator.
AB  - BACKGROUND: Instability is a crucial issue in severe post-traumatic elbow
      stiffness during complete-release surgery. This study aimed to evaluate the
      efficacy of ligament repair using a suture anchor in the operative treatment of
      severely stiff elbows for which a hinged external fixator was indicated. METHODS:
      We retrospectively reviewed 46 cases of severely stiff elbows (flexion arc <60
      degrees ) undergoing open release. During the operation, all 46 elbows were noted
      to have instability. Suture anchors were applied to restore the ligament if it
      was impossible to repair the ligament directly, and a hinged external fixator was
      simultaneously applied to protect the vulnerable ligament and facilitate
      rehabilitation. No allograft or autograft was used in any of our cases. The
      stability, arc of motion, Mayo Elbow Performance Score, ulnar nerve symptoms, and
      radiographs were evaluated. RESULTS: At a mean follow-up of 24.3 months, the
      postoperative Mayo Elbow Performance Score was 91 points, as compared with 63
      points preoperatively. The mean flexion arc improved from 25 degrees  to 126
      degrees . Three patients presented with moderate elbow instability when the
      hinged external fixator was removed; however, all of them regained stability by
      the last follow-up. Furthermore, 7 cases of new-onset nerve palsy were noted;
      however, all of them resolved with conservative management. None of the patients
      required secondary surgery for any reason. CONCLUSIONS: Repair of an avulsed
      collateral ligament with suture anchors and hinged external fixation was
      effective in restoring functional mobility in patients with severe post-traumatic
      elbow stiffness after complete release. This could be an option for treating
      ankylosed, severely or very severely stiff elbows.

PMID- 24927882
TI  - Is resection of the tendon edge necessary to enhance the healing process? An
      evaluation of the homeostasis of apoptotic and inflammatory processes in the
      distal 1 cm of a torn supraspinatus tendon: part I.
AB  - BACKGROUND: We hypothesize that the expression of proapoptotic and antiapoptotic
      molecules and cytokines is dependent on the distance from the torn supraspinatus
      tendon edge and this expression may influence its potential for healing. The aim
      of this work is to evaluate the expression of proapoptotic Bax molecule and
      caspases 3, 8, and 9; antiapoptotic Bcl-2 molecule; and proinflammatory tumor
      necrosis factor (TNF) alpha and anti-inflammatory interleukin 10 (IL-10) in 3
      sections taken from a 1-cm section of the edge of a torn supraspinatus tendon: 3
      mm distal and 3 mm proximal, as well as the remaining 4-mm middle section between
      them. METHODS: Nine patients, with a mean age of 58 years, were included in the
      study. All fulfilled strict inclusion criteria regarding the morphology of the
      tear and reconstruction technique. Samples were taken from the ruptured
      supraspinatus tendon at the time of arthroscopic repair. Quantitative real-time
      polymerase chain reaction assay was used for analysis. RESULTS: The expression of
      caspases 9, 8 and 3; Bax; and TNF-alpha significantly decreased from the distal
      to the proximal parts of the tendon edge (P < .05). However, a significant
      increase in Bcl-2 and IL-10 expression was also found in the same direction (P <
      .05). CONCLUSIONS: Tenocytes can reduce the expression of proapoptotic caspases
      3, 8, and 9 and Bax, as well as proinflammatory TNF-alpha, by increasing the
      expression of Bcl-2 and IL-10 within 1 cm of the supraspinatus edge in a distal
      to proximal direction. Resection 4 to 7 mm from the edge of the torn
      supraspinatus tendon may enhance the healing process by reaching a reasonable
      compromise between molecular homeostasis of apoptotic and inflammatory processes
      and mechanical aspects of rotator cuff reconstruction.

PMID- 24927883
TI  - Reverse shoulder arthroplasty for malignant tumors of proximal humerus.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) provides an alternative for
      shoulder girdle reconstruction after wide transarticular resection of the
      proximal humerus for malignant tumor. The aim of this study was to evaluate
      midterm outcomes of this therapeutic option. METHODS: Ten patients with RSA were
      included and reviewed with 24 months of minimum follow-up. Proximal resection of
      malignant tumor included the "V" deltoid insertion in 4 patients. The humeral
      stem was coated (with an allograft in 2 patients and a cement mantel in 3) or
      left uncoated (5 patients). RESULTS: At a mean follow-up of 42 months, among 8
      prosthesis available for evaluation (2 patients died), the Constant and Murley
      score averaged 52 points, the 11-item version of the Disabilities of the Arm,
      Shoulder and Hand (QuickDASH) score averaged 29.5 points, the Subjective Shoulder
      Value averaged 58%, and the Musculoskeletal Tumor Society score averaged 20.25
      points. Mean forward active elevation reached 122 degrees , external rotation at
      side was -2 degrees , and internal rotation was to L4. Three prostheses were
      unstable. The involvement of "V" deltoid insertion at surgery trended to worsen
      the clinical outcome. Atrophy of the anterior deltoid occurred in most of
      patients who had a previous transdeltoid biopsy. Radiographic evaluation found 1
      stem loosening, 1 stem at risk, and 3 scapular notches without glenoid loosening.
      CONCLUSION: Use of RSA after resection of a malignant tumor of the proximal
      humerus seems to be an acceptable option to preserve function. However,
      radiographic evolution is worrisome, and long-term study remains necessary to
      validate this therapeutic option with follow-up.

PMID- 24927884
TI  - Diagnostic accuracy of magnetic resonance imaging for subscapularis tendon tears
      using radial-slice magnetic resonance images.
AB  - BACKGROUND: Magnetic resonance imaging has low diagnostic accuracy for
      subscapularis tendon tears. This study investigated the utility of radial-slice
      magnetic resonance images for diagnosing subscapularis tendon tears. MATERIALS
      AND METHODS: We investigated 55 shoulders in 54 patients with rotator cuff tears
      evident during arthroscopic shoulder surgery. The intraoperative finding of a
      subscapularis tendon tear was compared with the identification of a subscapularis
      tendon tear on preoperative radial, transverse, and oblique sagittal images using
      a 3.0-T system. The sensitivity and specificity of diagnostic images generated
      using different imaging methods for subscapularis tendon tears were investigated.
      RESULTS: A subscapularis tendon tear was present in 38 shoulders (69.1%). When
      the diagnostic accuracy of the magnetic resonance images was compared with the
      arthroscopic findings, the radial images had 94.7% sensitivity and 82.4%
      specificity, the transverse images had 57.9% sensitivity and 100% specificity,
      and the oblique sagittal images had 60.5% sensitivity and 100% specificity.
      CONCLUSION: Radial-slice magnetic resonance images have high sensitivity for
      subscapularis tendon tears and are useful for diagnosing these lesions. In
      particular, the sensitivity for tears in the superior part of the subscapularis
      tendon is higher than that of conventional methods.

PMID- 24927885
TI  - Regulating cell death at, on, and in membranes.
AB  - Bcl-2 family proteins are central regulators of apoptosis. Various family members
      are located in the cytoplasm, endoplasmic reticulum, and mitochondrial outer
      membrane in healthy cells. However during apoptosis most of the interactions
      between family members that determine the fate of the cell occur at the membranes
      of intracellular organelles. It has become evident that interactions with
      membranes play an active role in the regulation of Bcl-2 family protein
      interactions. Here we provide an overview of various models proposed to explain
      how the Bcl-2 family regulates apoptosis and discuss how membrane binding affects
      the structure and function of each of the three categories of Bcl-2 proteins (pro
      apoptotic, pore-forming, and anti-apoptotic). We also examine how the Bcl-2
      family regulates other aspects of mitochondrial and ER physiology relevant to
      cell death. 

PMID- 24927896
TI  - Transcriptional regulation of Drosophila gonad formation.
AB  - The formation of the Drosophila embryonic gonad, involving the fusion of clusters
      of somatic gonadal precursor cells (SGPs) and their ensheathment of germ cells,
      provides a simple and genetically tractable model for the interplay between cells
      during organ formation. In a screen for mutants affecting gonad formation we
      identified a SGP cell autonomous role for Midline (Mid) and Longitudinals lacking
      (Lola). These transcriptional factors are required for multiple aspects of SGP
      behaviour including SGP cluster fusion, germ cell ensheathment and gonad
      compaction. The lola locus encodes more than 25 differentially spliced isoforms
      and we have identified an isoform specific requirement for lola in the gonad
      which is distinct from that in nervous system development. Mid and Lola work in
      parallel in gonad formation and surprisingly Mid overexpression in a lola
      background leads to additional SGPs at the expense of fat body cells. Our
      findings support the idea that although the transcription factors required by
      SGPs can ostensibly be assigned to those being required for either SGP
      specification or behaviour, they can also interact to impinge on both processes. 

PMID- 24927897
TI  - Biopsy-proven acute interstitial nephritis, 1993-2011: a case series.
AB  - BACKGROUND: Acute interstitial nephritis (AIN) is an important cause of acute
      kidney injury, especially in hospitalized patients. The cause and outcome of AIN,
      particularly that due to drugs, is changing with prevalent medication use. The
      effectiveness of steroids for treatment of AIN is debated. STUDY DESIGN: Case
      series. SETTING & PARTICIPANTS: 133 patients with biopsy-proven AIN from 1993
      through 2011 at a single center. OUTCOMES: Recovery of kidney function by 6
      months, either complete, partial, or none. Complete recovery was defined as
      improvement in serum creatinine level to within 25% of baseline (or < 1.4 mg/dL),
      and partial recovery, as a >= 50% decrease in serum creatinine level from its
      peak value but not reaching within 25% of its baseline value. RESULTS: Causes of
      AIN included drugs (70%), autoimmune diseases (20%), and infections (4%). Drug
      induced AIN was due to antibiotics in 49%, proton pump inhibitors (PPIs) in 14%,
      and nonsteroidal anti-inflammatory drugs (NSAIDs) in 11%. Overall, the top 3 drug
      causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%). Patients
      with drug-induced compared to non-drug-induced AIN were older and had higher
      baseline kidney function, but more severe acute kidney injury. Patients with PPI
      induced AIN were older, were less symptomatic, and had longer durations of drug
      exposure and longer delays in getting kidney biopsy and steroids than for
      antibiotic-induced or NSAID-induced AIN. At 6 months postbiopsy, 49% of patients
      with drug-induced AIN treated with steroids achieved complete recovery; 39%,
      partial recovery; and 12%, no recovery. Correlates of poor recovery included a
      longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and
      no recovery, respectively; P = 0.04) and longer delay in starting steroid therapy
      (8 vs 11 vs 35 days, respectively; P = 0.05). LIMITATIONS: Retrospective study,
      selection bias in patients who had kidney biopsy, single-center experience.
      CONCLUSIONS: The cause of AIN may be shifting; PPIs are emerging as an important
      contributor to this disease. Delays in discontinuation of the culprit drug and in
      initiating steroid treatment adversely affect recovery of kidney function.

PMID- 24927898
TI  - First-year outcomes of incident peritoneal dialysis patients in the United
      States.
AB  - BACKGROUND: Patterns of early outcomes in peritoneal dialysis (PD) are not well
      studied and dialysis providers need to establish a baseline of key outcomes for
      continuous quality improvement initiatives. STUDY DESIGN: Retrospective cohort
      study. SETTING & PARTICIPANTS: Incident PD patients from Fresenius Medical Care,
      North America from January 1 through December 31, 2009. FACTORS: Case-mix,
      comorbid illness, and baseline laboratory values. OUTCOMES: Death,
      hospitalization, peritonitis, and switch to hemodialysis (HD) within the first
      year on PD therapy. MEASUREMENTS: Event rates and outcome predictors. RESULTS: Of
      1,677 incident PD patients, 1,313 started on PD therapy and 367 switched from HD
      therapy within the first 90 days. Normalized first-year event rates for
      mortality, switch to HD therapy, peritonitis, and hospitalization were 10, 27,
      42, and 128 per 100 patient-years, respectively. 336 of 463 (72.6%) first
      peritonitis episodes and 637 of 939 (67.8%) first hospitalizations occurred
      within the first 6 months of PD treatment. Black race, higher body mass index,
      non-Hispanic ethnicity, peripheral vascular disease, and low weekly Kt/V
      associated with peritonitis risk. Dialysis vintage, female sex, diabetes,
      congestive heart failure, peripheral vascular disease, and history of limb
      amputation along with lower laboratory values for albumin, hemoglobin, and
      phosphorus and weekly Kt/V associated with hospitalization. Switchers to HD
      therapy (n=350) used central venous catheters 81.4% of the time as initial access
      (still 78.3% at 90 days later) because of lack of permanent access. LIMITATIONS:
      Residual confounding from unmeasured variables and exclusion of patients with a
      training day but who never started home PD therapy. CONCLUSIONS: Despite low
      first-year mortality, incident PD patients had high morbidity, particularly
      within the first 3-6 months. Increased focus to identify patients at greatest
      risk for peritonitis and hospitalization, as well as evaluation of care processes
      and implementation of preventive strategies, is required. Access planning for
      transition to HD therapy needs more attention, even during the first PD year.

PMID- 24927899
TI  - Optimized dosing of cefazolin in patients treated with nocturnal home
      hemodialysis.

PMID- 24927900
TI  - Natural-focal diseases: mapping experience in Russia.
AB  - BACKGROUND: Natural-focal diseases constitute a serious hazard for human health.
      Agents and vectors of such diseases belong to natural landscapes. The aim of this
      study is to identify the diversity and geography of natural-focal diseases in
      Russia and to develop cartographic approaches for their mapping, including
      mathematical-cartographical modeling. Russian medico-geographical mapping of
      natural-focal diseases is highly developed regionally and locally but extremely
      limited at the national level. To solve this problem, a scientific team of the
      Faculty of Geography at Lomonosov Moscow State University has developed and
      implemented a project of a medico-geographical Atlas of Russia "Natural-Focal
      Diseases". METHODS: The mapping is based on medical statistics data. The Atlas
      contains a series of maps on disease incidence, long-term dynamics of disease
      morbidity, etc. In addition, other materials available to the authors were used:
      mapping of the natural environment, field data, archival materials, analyzed
      satellite images, etc. The maps are processed using ArcGIS (ESRI) software
      application. Different methods of rendering of mapped phenomena are used
      (geographical ranges, diagrams, choropleth maps etc.). RESULTS: A series of
      analytical, integrated, and synthetic maps shows disease incidence in the
      population at both the national and regional levels for the last 15 years. Maps
      of the mean annual morbidity of certain infections and maps of morbidity dynamics
      and nosological profiles allow for a detailed analysis of the situation for each
      of 83 administrative units of the Russian Federation. The degree of epidemic
      hazard in Russia by natural-focal diseases is reflected in a synthetic medico
      geographical map that shows the degree of epidemic risks due to such diseases in
      Russia and allows one to estimate the risk of disease manifestation in a given
      region. CONCLUSIONS: This is the first attempt at aggregation and public
      presentation of diverse and multifaceted information about natural-focal diseases
      in Russia. Taken in entirety, the maps that have been prepared for the Atlas will
      enable researchers to evaluate the stability of epidemic manifestation of
      individual diseases and the susceptibility of a given territory to disease
      transmission. The results can be used for sanitary monitoring and disease
      prevention.

PMID- 24927901
TI  - Subject-specific real-time respiratory liver motion compensation method for
      ultrasound-MRI/CT fusion imaging.
AB  - PURPOSE: Ultrasound-MRI/CT fusion imaging is widely used in minimal invasive
      surgeries, such as liver biopsy and tumor ablation. However, respiration-induced
      quasi-periodic liver motion and deformation cause unacceptable misalignment of
      the fusion images (i.e., fusion error). A subject-specific liver motion model
      based on skin-mounted position sensor and corresponding ultrasound liver image
      sequence was developed to compensate for liver motion. METHODS: External
      surrogate respiratory motion signal is used to predict internal liver motion. An
      electromagnetic position sensor fixed on abdominal skin is introduced to track
      the respiratory motion, and 2D ultrasound images are used to track the liver
      motion synchronously. Based on these measurements, a subject-specific model
      describing the relationship of respiratory skin motion and internal liver motion
      is built and applied in real time (ultrasound-MRI/CT fusion imaging system) to
      predict and to compensate for the liver motion due to respiratory movement.
      Feasibility experiments and clinical trials were carried out on a phantom and
      eight volunteers. RESULTS: Qualitative and quantitative analyses and visual
      inspections performed by experienced clinicians show that the proposed model
      could effectively compensate for the liver motion, and the ratio of motion
      compensated fusion error to the original varied from 10 % (0.96/9.40 mm) to 28 %
      (2.90/10.22 mm). CONCLUSIONS: An online liver motion modeling and compensation
      method was developed that provides surgeons with stable and accurate
      multimodality fusion images in real time.

PMID- 24927902
TI  - A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a
      prognostic indicator of poor survival.
AB  - Sox2 overlapping transcript (Sox2ot) is a long noncoding RNA (lncRNA), localized
      on human chromosome 3q26.33, which is frequently amplified in lung squamous cell
      carcinomas (SCCs). However, its roles in lung cancer remain under investigation.
      In this study, we found that Sox2ot was up-regulated over two folds in 53.01% of
      human primary lung cancers (44/83). The expression level of Sox2ot is
      significantly higher in SCCs than that in adenocarcinomas (ADCs) of the lung.
      Further study found high Sox2ot expression predicted poor survival in lung cancer
      patients (P=0.0053), implying Sox2ot is a novel prognostic factor. In two human
      lung cancer cell lines, HCC827 and SK-MES-1, knocking down Sox2ot inhibited cell
      proliferation by inducing G2/M arrest, with a concomitant decrease of cells in S
      phase. Reduced protein levels of Cyclin B1 and Cdc2 were also observed.
      Importantly, knocking down Sox2ot decreased EZH2 expression and reintroduction of
      EZH2 allowed Sox2ot knockdown cells progressed through G2/M phase, which
      correlates with the restoration of Cyclin B1 and Cdc2 expressions. Altogether,
      our data suggested that Sox2ot plays an important role in regulating lung cancer
      cell proliferation, and may represent a novel prognostic indicator for the
      disease. 

PMID- 24927903
TI  - Preparation and sonodynamic activities of water-soluble tetra-alpha-(3
      carboxyphenoxyl) zinc(II) phthalocyanine and its bovine serum albumin conjugate.
AB  - Sonodynamic therapy (SDT) is a new approach for cancer treatment, involving the
      synergistic effect of ultrasound and certain chemical compounds termed as
      sonosensitizers. A water-soluble phthalocyanine, namely tetra-alpha-(3
      carboxyphenoxyl) zinc(II) phthalocyanine (ZnPcC4), has been prepared and
      characterized. The interactions between ZnPcC4 and bovine serum albumin (BSA)
      were also investigated by absorption and fluorescence spectroscopy. It was found
      that there were strong interactions between ZnPcC4 and BSA with a binding
      constant of 6.83*10(7)M(-1). A non-covalent BSA conjugate of ZnPcC4 (ZnPcC4-BSA)
      was prepared. Both ZnPcC4 and ZnPcC4-BSA exhibited efficient sonodynamic
      activities against HepG2 human hepatocarcinoma cells. Compared with ZnPcC4,
      conjugate ZnPcC4-BSA showed a higher sonodynamic activity with an IC50 value of
      7.5MUM. Upon illumination with ultrasound, ZnPcC4-BSA can induce an increase of
      intracellular reactive oxygen species (ROS) level, resulting in cellular
      apoptosis. The results suggest that the albumin conjugates of zinc(II)
      phthalocyanines functionalized with carboxyls can serve as promising
      sonosensitizers for sonodynamic therapy. 

PMID- 24927904
TI  - Ultrasound-assisted extraction of amino acids from grapes.
AB  - Recent cultivar techniques on vineyards can have a marked influence on the final
      nitrogen content of grapes, specifically individual amino acid contents.
      Furthermore, individual amino acid contents in grapes are related to the final
      aromatic composition of wines. A new ultrasound-assisted method for the
      extraction of amino acids from grapes has been developed. Several extraction
      variables, including solvent (water/ethanol mixtures), solvent pH (2-7),
      temperature (10-70 degrees C), ultrasonic power (20-70%) and ultrasonic frequency
      (0.2-1.0s(-)(1)), were optimized to guarantee full recovery of the amino acids
      from grapes. An experimental design was employed to optimize the extraction
      parameters. The surface response methodology was used to evaluate the effects of
      the extraction variables. The analytical properties of the new method were
      established, including limit of detection (average value 1.4mmolkg(-)(1)), limit
      of quantification (average value 2.6mmolkg(-)(1)), repeatability (average
      RSD=12.9%) and reproducibility (average RSD=15.7%). Finally, the new method was
      applied to three cultivars of white grape throughout the ripening period. 

PMID- 24927905
TI  - International Conference on Nutrition and the Brain--Preface.

PMID- 24927906
TI  - Critical levels of brain atrophy associated with homocysteine and cognitive
      decline.
AB  - Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of
      beneficial effects on cognition in older adults with cognitive impairment or
      Alzheimer's disease. This article reviews the role of Hcy in cognitive decline.
      It also considers some reasons why meta-analyses have failed to find effects of B
      vitamin treatment. Findings from the successful VITACOG trial are examined from a
      new perspective of critical levels of Hcy and brain atrophy that may impact on
      the efficacy of B-vitamin treatment. It appears that there is a critical level of
      brain shrinkage, possibly mediated by elevated Hcy, which when reached, results
      in cognitive decline, especially in episodic memory performance. Supplements,
      food sources, and effects of folic acid fortification are discussed in relation
      to B12 deficiency. 

PMID- 24927907
TI  - Diffuse alveolar hemorrhage as a presentation of acute poststreptococcal
      glomerulonephritis.

PMID- 24927908
TI  - Sarcoidosis presenting with pancytopenia.

PMID- 24927909
TI  - Clinical outcomes with beta-blockers for myocardial infarction: a meta-analysis
      of randomized trials.
AB  - BACKGROUND: Debate exists about the efficacy of beta-blockers in myocardial
      infarction and their required duration of usage in contemporary practice.
      METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials
      evaluating beta-blockers in myocardial infarction enrolling at least 100
      patients. The primary outcome was all-cause mortality. Analysis was performed
      stratifying trials into reperfusion-era (> 50% undergoing reperfusion or
      receiving aspirin/statin) or pre-reperfusion-era trials. RESULTS: Sixty trials
      with 102,003 patients satisfied the inclusion criteria. In the acute myocardial
      infarction trials, a significant interaction (Pinteraction = .02) was noted such
      that beta-blockers reduced mortality in the pre-reperfusion (incident rate ratio
      [IRR] 0.86; 95% confidence interval [CI], 0.79-0.94) but not in the reperfusion
      era (IRR 0.98; 95% CI, 0.92-1.05). In the pre-reperfusion era, beta-blockers
      reduced cardiovascular mortality (IRR 0.87; 95% CI, 0.78-0.98), myocardial
      infarction (IRR 0.78; 95% CI, 0.62-0.97), and angina (IRR 0.88; 95% CI, 0.82
      0.95), with no difference for other outcomes. In the reperfusion era, beta
      blockers reduced myocardial infarction (IRR 0.72; 95% CI, 0.62-0.83) (number
      needed to treat to benefit [NNTB] = 209) and angina (IRR 0.80; 95% CI, 0.65-0.98)
      (NNTB = 26) at the expense of increase in heart failure (IRR 1.10; 95% CI, 1.05
      1.16) (number needed to treat to harm [NNTH] = 79), cardiogenic shock (IRR 1.29;
      95% CI, 1.18-1.41) (NNTH = 90), and drug discontinuation (IRR 1.64; 95% CI, 1.55
      1.73), with no benefit for other outcomes. Benefits for recurrent myocardial
      infarction and angina in the reperfusion era appeared to be short term (30 days).
      CONCLUSIONS: In contemporary practice of treatment of myocardial infarction, beta
      blockers have no mortality benefit but reduce recurrent myocardial infarction and
      angina (short-term) at the expense of increase in heart failure, cardiogenic
      shock, and drug discontinuation. The guideline authors should reconsider the
      strength of recommendations for beta-blockers post myocardial infarction.

PMID- 24927910
TI  - Hypoglycemic hemiparesis: the stroke masquerader.

PMID- 24927911
TI  - Improving adherence for management of acute exacerbation of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Clinical practice guidelines recommend 40-60 mg of prednisone
      equivalent for 10-14 days for patients with acute exacerbations of chronic
      obstructive pulmonary disease (COPD). However, the amount of corticosteroid
      prescribed varies widely in clinical practice. Using the electronic health
      record, we implemented an evidence-based order set to standardize treatment of
      patients hospitalized with acute exacerbations of COPD. METHODS: This is a pre-
      and post-intervention study on patients hospitalized between January 1, 2009 and
      September 30, 2012 with primary discharge diagnosis of COPD (International
      Classification of Diseases, 9(th) Revision code: 491.xx, 492.xx, and 496) and
      receipt of at least one dose of corticosteroid at our tertiary care hospital.
      Data on baseline demographics, dose of corticosteroid in prednisone equivalent
      administered during the first 48 hours and during the entire hospitalizations
      were collected from the electronic health record. Evidence-based guidelines were
      used to build and implement acute exacerbations of COPD management electronic
      ordersets in our electronic health record, Epic (Verona, WI). We divided the
      study into 2 time periods (January 1, 2009 through February 28, 2011 as pre- [n =
      203] and March 1, 2011 through September 30, 2012 as post-intervention periods [n
      = 217]). The primary outcome measure was corticosteroid dose administered in the
      first 48 hours. Secondary outcome measures were corticosteroid dosage during the
      entire hospitalization, length of stay, hospital follow-up rates, and 30-day
      readmission rates. RESULTS: A total of 420 patients with acute exacerbations of
      COPD were included in the study. In the post-intervention period, the median
      amount of corticosteroid used in the first 48 hours was significantly reduced
      (306.2 mg vs 156.25 mg, P < .0001), as was that used during the entire
      hospitalization (352.5 mg vs 175 mg, P < .0001). There was no difference in
      hospital follow-up rates, length of stay, or 30-day readmission rates between the
      2 periods. CONCLUSIONS: Evidence-based electronic ordersets improve compliance
      with clinical practice guidelines and reduce the total dose of corticosteroid
      administered in patients hospitalized with acute exacerbations of COPD.

PMID- 24927912
TI  - Serious and commonly overlooked side effect of prolonged use of PPI.

PMID- 24927913
TI  - Age-specific bone tumour incidence rates are governed by stem cell exhaustion
      influencing the supply and demand of progenitor cells.
AB  - Knudson's carcinogenic model, which simulates incidence rates for retinoblastoma,
      provides compelling evidence for a two-stage mutational process. However, for
      more complex cancers, existing multistage models are less convincing. To fill
      this gap, I hypothesize that neoplasms preferentially arise when stem cell
      exhaustion creates a short supply of progenitor cells at ages of high
      proliferative demand. To test this hypothesis, published datasets were employed
      to model the age distribution of osteochondroma, a benign lesion, and
      osteosarcoma, a malignant one. The supply of chondrogenic stem-like cells in
      femur growth plates of children and adolescents was evaluated and compared with
      the progenitor cell demand of longitudinal bone growth. Similarly, the supply of
      osteoprogenitor cells from birth to old age was compared with the demands of bone
      formation. Results show that progenitor cell demand-to-supply ratios are a good
      risk indicator, exhibiting similar trends to the unimodal and bimodal age
      distributions of osteochondroma and osteosarcoma, respectively. The hypothesis
      also helps explain Peto's paradox and the finding that taller individuals are
      more prone to cancers and have shorter lifespans. The hypothesis was tested, in
      the manner of Knudson, by its ability to convincingly explain and demonstrate,
      for the first time, a bone tumour's bimodal age-incidence curve. 

PMID- 24927915
TI  - Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor
      cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways.
AB  - Human endothelial progenitor cells (hEPCs) derived from bone marrow play a
      crucial in the prevention of ischemic injuries in the course of postnatal
      neovasculogenesis. Frequent fish oil (FO) consumption is reportedly associated
      with a significantly lower incidence of cardiovascular disease. However, the
      molecular mechanisms of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)
      are not well elucidated, and the beneficial effect of FO consumption on
      neovasculogenesis has not been demonstrated yet. In the current study, we
      investigated the effects of EPA/DHA and FO consumption on neovasculogenesis by
      using vascular tube formation assay, Western blotting, real-time polymerase chain
      reaction, immunohistochemical staining and Doppler imaging in both in vitro and
      in vivo models. The results demonstrate that EPA and DHA dose-dependently enhance
      the neovasculogenesis and cell migration of hEPCs in vitro. The mechanisms of
      action included up-regulation of the c-kit protein as well as the phosphorylation
      of the ERK1/2, Akt and endothelial nitric oxide synthase signaling molecules in
      hEPCs. Furthermore, EPA significantly suppressed the expression of microRNA 221
      in vitro. In experimental animal models, FO consumption significantly induced the
      formation of new blood vessels (neovasculogenesis) and prevented ischemia. Taken
      together, it is suggested that FO consumption enhances neovasculogenesis mainly
      through the effects of EPA in hEPCs, thereby exerting a preventive effect against
      ischemic injury.

PMID- 24927914
TI  - Inflammation-induced fetal growth restriction in rats is associated with altered
      placental morphometrics.
AB  - INTRODUCTION: Evidence links alterations in placental shape and size to fetal
      growth restriction (FGR). Here we determined whether alterations in placental
      morphometrics are linked to FGR induced by abnormal maternal inflammation.
      METHODS: We used an inflammation-induced model of FGR in which pregnant rats
      receive lipopolysaccharide (LPS) on gestational days (GD) 13.5-16.5. Fetal
      weights were matched to various parameters of placental morphometrics including
      weight, area, minor and major axes lengths and thickness. RESULTS: Compared with
      saline administration, LPS administration was associated with altered placental
      morphometrics, including reduced placental weight, decreased placental area and a
      trend towards reduced placental thickness. When data were dichotomized as FGR or
      normal-sized fetuses within treatment groups, a significant increase in the
      placental-weight-to-fetal-weight ratio and placental thickness was observed only
      in the saline-associated FGR subgroup. Multivariable linear regression revealed
      that the lengths of the major and minor placental axes were predictors of fetal
      weight, regardless of treatment modality. Subgroup regression analysis by
      treatment revealed that the lengths of the major and minor placental axes were
      predictors of fetal weight in the saline-treatment group while only the minor
      placental axis was a predictor of fetal weight in the LPS cohort. Finally,
      placental area and the length of the minor placental axis were correlated with
      implantation site location only in the saline-treatment group.
      DISCUSSION/CONCLUSION: These findings indicate that inflammation-induced FGR is
      associated with alterations in placental morphometrics. Our data reveal that the
      mechanisms leading to inflammation-induced FGR may be different from the
      mechanisms leading to idiopathic FGR.

PMID- 24927917
TI  - Prickle1 is necessary for the caudal migration of murine facial branchiomotor
      neurons.
AB  - Facial branchiomotor neurons (FBMs) of vertebrates typically develop in
      rhombomere 4 (r4), and in mammals and several other vertebrate taxa, migrate
      caudally into r6 and subsequently laterally and ventrally to the pial surface.
      How similar or dissimilar these migratory processes between species are at a
      molecular level remains unclear. In zebrafish and mouse, mutations in certain PCP
      genes disrupt normal caudal migration of FBMs. Zebrafish prickle1a (prickle-like
      1a) and prickle1b, two orthologs of Prickle1, act non-cell-autonomously and cell
      autonomously, respectively, to regulate FBM migration. Here, we show that, in
      Prickle1 (C251X/C251X) mice which have reduced Prickle1 expression, the caudal
      migration of FBMs is affected. Most FBM neurons do not migrate caudally along the
      floor plate. However, some neurons perform limited caudal migration such that the
      neurons eventually lie near the pial surface from r4 to anterior r6. FBMs in
      Prickle1 (C251X/C251X) mice survive until P0 and form an ectopic nucleus dorsal
      to the olivo-cochlear efferents of r4. Ror2, which modifies the PCP pathway in
      other systems, is expressed by the migrating mouse FBMs, but is not required for
      FBM caudal migration. Our results suggest that, in mice, Prickle1 is part of a
      molecular mechanism that regulates FBM caudal migration and separates the FBM and
      the olivo-cochlear efferents. This defective caudal migration of FBMs in
      Prickle1C251X mutants resembles Vangl2 mutant defects. In contrast to other
      developing systems that show similar defects in Prickle1, Wnt5a and Ror2, the
      latter two only have limited or no effect on FBM caudal migration. 

PMID- 24927919
TI  - Phenotypic characterization of craniofacial bone marrow stromal cells: unique
      properties of enhanced osteogenesis, cell recruitment, autophagy, and apoptosis
      resistance.
AB  - Previous studies have shown that craniofacial bone marrow stromal cells (MSCs)
      have greater osteogenic potential than appendicular bone MSCs. However, detailed
      phenotypic characterization of MSCs from bone marrow in the different sites
      remains unclear. To investigate bone repair and regeneration of craniofacial MSCs
      and the regulatory mechanisms underlying their unique properties, we compared
      osteogenesis, cell recruitment, autophagy, and apoptosis resistance of MSCs from
      the mandible (M-MSCs) to those from tibia (T-MSCs) in vitro and in vivo. Compared
      with T-MSCs, M-MSCs formed more colonies, possessed stronger proliferation
      activity, exhibited higher expression of pluripotency genes such as Oct4 and
      Nanog, and held stronger osteogenic differentiation in osteogenic medium.
      Moreover, M-MSCs had greater autophagy and anti-apoptotic capacities than T-MSCs
      under hypoxia and serum deprivation conditions. M-MSCs were found to be more
      capable of recruiting more MSCs than T-MSCs. When these MSCs were transplanted
      into mandible critical-sized defects, more bone formed in the M-MSC-treated
      animals than in their T-MSC counterparts. Collectively, these findings reveal
      that MSCs have unique characteristics and bone-repairing properties from the
      mandible as compared with those from tibia, presumably by enhanced osteogenic
      potential, cell recruitment, autophagy and apoptosis resistance. 

PMID- 24927918
TI  - Characterization and evaluation of mesenchymal stem cells derived from human
      embryonic stem cells and bone marrow.
AB  - Embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have been studied
      for years as primary cell sources for regenerative biology and medicine. MSCs
      have been derived from cell and tissue sources, such as bone marrow (BM), and
      more recently from ESCs. This study investigated MSCs derived from BM, H1- and H9
      ESC lines in terms of morphology, surface marker and growth factor receptor
      expression, proliferative capability, modulation of immune cell growth and
      multipotency, in order to evaluate ESC-MSCs as a cell source for potential
      regenerative applications. The results showed that ESC-MSCs exhibited spindle
      shaped morphology similar to BM-MSCs but of various sizes, and flow cytometric
      immunophenotyping revealed expression of characteristic MSC surface markers on
      all tested cell lines except H9-derived MSCs. Differences in growth factor
      receptor expression were also shown between cell lines. In addition, ESC-MSCs
      showed greater capabilities for cell proliferation, and suppression of leukocyte
      growth compared to BM-MSCs. Using standard protocols, induction of ESC-MSC
      differentiation along the adipogenic, osteogenic, or chondrogenic lineages was
      less effective compared to that of BM-MSCs. By adding bone morphogenetic protein
      7 (BMP7) into transforming growth factor beta 1 (TGFbeta1)-supplemented induction
      medium, chondrogenesis of ESC-MSCs was significantly enhanced. Our findings
      suggest that ESC-MSCs and BM-MSCs show differences in their surface marker
      profiles and the capacities of proliferation, immunomodulation, and most
      importantly multi-lineage differentiation. Using modified chondrogenic medium
      with BMP7 and TGFbeta1, H1-MSCs can be effectively induced as BM-MSCs for
      chondrogenesis. 

PMID- 24927920
TI  - Kruppel-like factor 4 expression in osteoblasts represses osteoblast-dependent
      osteoclast maturation.
AB  - Kruppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor with a
      restricted expression pattern during skeletal development. We have previously
      shown that KLF4 represses osteoblast mineralization concomitant with a down
      regulation in the expression of a number of osteoblastic genes, both in vivo and
      in vitro. In addition to the cell-autonomous effects of KLF4 in osteoblasts,
      transgenic osteoblastic-KLF4 mice show severe defects in osteoclast maturation.
      Wild-type bone-marrow-derived macrophages co-cultured with KLF4-expressing
      osteoblasts exhibit reduced formation of multinuclear osteoclasts as compared
      with control cultures overexpressing green fluorescent protein. Significantly,
      the transduction of Runx2, a master regulator of osteoblastogenesis, together
      with KLF4 into osteoblasts restores the reduction in osteoclastogenesis induced
      by KLF4 alone. Various extracellular matrix molecules are down-regulated by KLF4
      overexpression but this down-regulation can be partially restored by the co
      transduction of Runx2. These results suggest that osteoblastic-KLF4 affects
      osteoclast maturation by regulating cell-matrix interactions and reinforce the
      importance of the regional down-regulation of KLF4 expression in the subset of
      osteoblasts for normal skeletal modeling and remodeling. 

PMID- 24927922
TI  - A critical ACR appropriateness Criteria omission.

PMID- 24927921
TI  - Dose perturbation due to catheter materials in high-dose-rate interstitial
      (192)Ir brachytherapy.
AB  - PURPOSE: Catheters made of either metal or plastic are currently used in
      brachytherapy treatment to insert radiative sources into patients. However, the
      radiation dose perturbations due to catheter attenuation are not taken into
      account in treatment planning. The purpose of this work is to quantify the
      effects of catheter composition on dose distribution and study their impacts on
      the overall treatment with high-dose-rate (192)Ir sources. METHODS AND MATERIALS:
      Dose perturbations are first studied in a simplified case consisting of two
      parallel catheters. The catheter wall is either composed of stainless steel or
      polyoxymethylene. The attenuations are studied as the distance between the two
      catheters is varied from 5 to 30 mm. Dose perturbations resulting from
      irradiation are evaluated with a Monte Carlo GEANT4 dose calculation algorithm.
      The dose differences are further investigated with seven typical high-dose-rate
      prostate treatment plans involving 17 catheters. RESULTS: The dose differences
      compared with water in the simplified case reach -4.3 +/- 0.1% for stainless
      steel and 1.7 +/- 0.5% for polyoxymethylene at 10 mm above the source when the
      catheters are separated by a distance of 5 mm. Dose perturbations are reduced in
      real treatment plans because of the contributions of the many dwell positions.
      Stainless steel and polyoxymethylene catheters induce on an average a dose
      difference of -1.3 +/- 0.3% and 0.1 +/- 0.2%, respectively in the target.
      CONCLUSIONS: The dose differences reported in this work do not warrant any
      changes in the clinical procedures.

PMID- 24927923
TI  - Response to Dr Sabater.

PMID- 24927924
TI  - Novel BCR-ABL1 fusion identified by targeted next-generation sequencing in a
      patient with an atypical myeloproliferative neoplasm.
AB  - An unusual case of a BCR-ABL1-positive myeloproliferative neoplasm is presented
      with discordant molecular and cytogenetic characterization at diagnosis. More
      extensive molecular characterization of the fusion messenger RNA transcript using
      a next-generation sequencing approach identified a novel BCR-calcineurin-binding
      protein 1-ABL1 variant, which has not been described previously. This case
      highlights the potential utility of next-generation sequencing for a single
      target application to resolve rare and unusual tumor genetic variants when
      standard molecular diagnostic methods are inconclusive. Although the relationship
      of this novel BCR-ABL1 fusion to the atypical pathologic features and initially
      suboptimal therapeutic response profile remains speculative, this case indicates
      that accurate molecular characterization of rare variants has diagnostic and
      potentially prognostic relevance.

PMID- 24927925
TI  - Prediction of adaptation difficulties by country of origin, cumulate psychosocial
      stressors and attitude toward integrating: a Swedish study of first-generation
      immigrants from Somalia, Vietnam and China.
AB  - BACKGROUND: Different types of accumulated stress have been found to have
      negative consequences for immigrants' capacity to adapt to the new environment.
      It remains unclear which factors have the greatest influence. AIMS: The study
      investigated whether immigrants' experience of great difficulty in adapting to a
      new country could best be explained by (1) country of origin, (2) exposure to
      accumulated stressors before arrival or (3) after arrival in the new country
      and/or (4) reserved attitude toward integrating into the new society. METHODS:
      The 119 first-generation immigrants from Somalia, Vietnam and China, living in
      Malmo, Sweden, were interviewed in a standardized manner. RESULTS: Experiencing
      great difficulty in adapting to Sweden was independent of length of residence,
      but significantly related to all four influences, studied one at a time. Country
      of origin was also related to stressors and attitude. When the effects of the
      other influences were mutually controlled for, only exposure to accumulated
      stressors in Sweden (and especially experiencing
      discrimination/xenophobia/racism) accounted for great adaptation difficulty.
      Stressors in Sweden had a greater effect if the immigrant had been exposed to
      stressors earlier. CONCLUSIONS: Immigrants' long-term experiences of great
      difficulty in adapting to a new country were explained primarily by exposure to
      accumulated stressors while moving to and living in the new country, rather than
      by their backgrounds or attitudes toward integrating. This suggests promoting
      strategies to avoid discrimination and other stressors in the host country.

PMID- 24927926
TI  - Results of a pragmatic effectiveness-implementation hybrid trial of the Family
      Check-up in community mental health agencies.
AB  - This study reports the results of a pragmatic effectiveness-implementation hybrid
      trial of the Family Check-Up (FCU) conducted in three community mental health
      agencies with 40 participating therapists. Seventy-one families with children
      between 5 and 17 years of age participated. Intervention fidelity and level of
      adoption were acceptable; families reported high service satisfaction; and
      therapists reported high acceptability. Families in the FCU condition experienced
      significantly reduced youth conduct problems in comparison to usual care and
      completion of the FCU resulted in larger effects. This study provides promising
      evidence that implementing the FCU in community mental health agencies has the
      potential to improve youth behavior outcomes. 

PMID- 24927927
TI  - Dopamine D(2)/D(3) receptor binding of [(123)I]epidepride in risperidone
      treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT
      neuroimaging.
AB  - INTRODUCTION: Epidepride is a compound with an affinity in picomolar range for
      D2/D3 receptors. The aim of this work was designed to investigate the diagnostic
      possibility of [(123)I]epidepride imaging platform for risperidone-treatment
      chronic MK-801-induced rat schizophrenia model. METHODS: Rats received repeated
      administration of MK-801 (dissolved in saline, i.p., 0.3 mg/kg/day) or saline for
      4 weeks. After 1-week administration of MK-801, rats in MK-801+risperidone group
      received risperidone (0.5 mg/kg/day) intraperitoneally 15 min prior to MK-801
      administration for the rest of 3-week treatment. We obtained serial
      [(123)I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of
      specific binding in striatum and midbrain. RESULTS: Risperidone reversed chronic
      MK-801-induced decrease in social interaction duration. IHC and ELISA analysis
      showed consistent results that chronic MK-801 treatment significantly decreased
      striatal and midbrain D2R expression but repeated risperidone administration
      reversed the effect of MK-801 treatment. In addition, [(123)I]epidepride
      nanoSPECT/CT neuroimaging revealed that low specific [(123)I]epidepride binding
      ratios caused by MK-801 in striatum and midbrain were statistically alleviated
      after 1- and 2-week risperidone administration, respectively. CONCLUSIONS: We
      established a rat schizophrenia model by chronic MK-801 administration for 4
      weeks. [(123)I]Epidepride nanoSPECT neuroimaging can trace the progressive
      alteration of D2R expression in striatum and midbrain caused by long-lasting MK
      801 treatment. Besides diagnosing illness stage of disease, [(123)I]epidepride
      can be a useful tool to evaluate therapeutic effects of antipsychotic drug in
      chronic MK-801-induced rat schizophrenia model.

PMID- 24927928
TI  - Risk-adjusted outcome prediction with initial post-cardiac arrest illness
      severity: implications for cardiac arrest survivors being considered for early
      invasive strategy.
AB  - BACKGROUND: Early CATH is recommended for cardiac arrest survivors with STEMI or
      suspicion for coronary ischemia. Comatose patients are at risk of death from
      neurologic injury irrespective of CATH, but post-procedural mortality data do not
      distinguish between causes of death. Pittsburgh Post Cardiac Arrest Category
      (PCAC) is a validated, early post-cardiac arrest illness severity score based on
      initial cardiopulmonary dysfunction and neurologic examination. We evaluated the
      association between early coronary angiography (CATH) and patient outcome after
      adjusting for initial post-cardiac arrest illness severity. METHODS:
      Retrospective study of a prospective cardiac arrest database at a single site. We
      included 1011 adult survivors of non-traumatic in-hospital or out-of-hospital
      cardiac arrest from 2005 to 2012, then stratified by PCAC and immediate CATH.
      Logistic regression tested the association between immediate CATH and patient
      outcomes, adjusting for PCAC. RESULTS: Overall, 273 (27%) received immediate
      CATH. Patients with immediate CATH had higher proportions of good outcome in all
      but the most severe stratum of illness severity (11% vs. 6%; p=0.11). The primary
      mode of death was neurologic for all but the least severe stratum. Adjusting for
      PCAC, immediate CATH was associated with favorable discharge disposition (OR
      1.92; 95%CI 1.20, 3.07; p=0.006) and modified Rankin scale (OR 1.95; 95%CI 1.12,
      3.38; p=0.02). CONCLUSIONS: The benefit of CATH is less clear in the most severe
      stratum of illness, in which the high risk of mortality is primarily from
      neurologic causes. PCAC is a risk-stratification tool that provides pre
      procedural risk-adjusted outcome prediction for post-cardiac arrest patients
      being evaluated for immediate CATH.

PMID- 24927929
TI  - ESHRE task force on ethics and Law22: preimplantation genetic diagnosis.
AB  - This Task Force document discusses some relatively unexplored ethical issues
      involved in preimplantation genetic diagnosis (PGD). The document starts from the
      wide consensus that PGD is ethically acceptable if aimed at helping at-risk
      couples to avoid having a child with a serious disorder. However, if understood
      as a limit to acceptable indications for PGD, this 'medical model' may turn out
      too restrictive. The document discusses a range of possible requests for PGD that
      for different reasons fall outwith the accepted model and argues that instead of
      rejecting those requests out of hand, they need to be independently assessed in
      the light of ethical criteria. Whereas, for instance, there is no good reason for
      rejecting PGD in order to avoid health problems in a third generation (where the
      second generation would be healthy but faced with burdensome reproductive choices
      if wanting to have children), using PGD to make sure that one's child will have
      the same disorder or handicap as its parents, is ethically unacceptable. 

PMID- 24927930
TI  - Resident involvement in postoperative conversations: an underused opportunity.
AB  - BACKGROUND: Because of established attending-patient and family relationships and
      time constraints, residents are often excluded from the immediate postoperative
      conversation with family. Interpersonal and communication skills are a core
      competency, and the postoperative conversation is an opportunity to develop these
      skills. Our objective is to assess attitudes, experience, and comfort regarding
      resident participation during postoperative conversations with families.
      MATERIALS AND METHODS: Residents and attending surgeons in an academic surgery
      center were surveyed regarding resident involvement in the postoperative
      conversation with families. Paper surveys were administered anonymously.
      Nonparametric statistics compared responses. RESULTS: There were 45 survey
      respondents (23 residents, 22 attendings). All residents rated postoperative
      conversations with families, as "important" or "very important". Residents
      reported being "comfortable" or "very comfortable" with postoperative
      conversations. However, on average, residents reported fewer than 10
      postoperative conversation experiences per year. Feedback was received by <30% on
      postoperative communication skills, but 88% wanted feedback. Most attendings
      reported it is "important" or "very important" for residents to communicate well
      with families during postoperative conversations, but rated residents'
      performance as significantly lower than the residents' self-assessments (P <
      0.001). Attendings on average were only "somewhat comfortable" or "moderately
      comfortable" with residents conducting postoperative conversations with families,
      and only 68% reported allowing residents to do so. When bad news was involved,
      only 27% allowed resident participation. Most attendings (86%) believed residents
      need more opportunities with postoperative conversations. CONCLUSIONS: Although
      most residents reported being comfortable with postoperative conversations, these
      survey results indicate that they have few opportunities. Developing a workshop
      on communication skills focused on the postoperative conversations with families
      may be beneficial.

PMID- 24927931
TI  - Cortical and Clonal Contribution of Tbr2 Expressing Progenitors in the Developing
      Mouse Brain.
AB  - The individual contribution of different progenitor subtypes towards the mature
      rodent cerebral cortex is not fully understood. Intermediate progenitor cells
      (IPCs) are key to understanding the regulation of neuronal number during cortical
      development and evolution, yet their exact contribution is much debated.
      Intermediate progenitors in the cortical subventricular zone are defined by
      expression of T-box brain-2 (Tbr2). In this study we demonstrate by using the
      Tbr2(Cre) mouse line and state-of-the-art cell lineage labeling techniques, that
      IPC derived cells contribute substantial proportions 67.5% of glutamatergic but
      not GABAergic or astrocytic cells to all cortical layers including the earliest
      generated subplate zone. We also describe the laminar dispersion of clonally
      derived cells from IPCs using a recently described clonal analysis tool (CLoNe)
      and show that pair-generated cells in different layers cluster closer (142.1 +/-
      76.8 MUm) than unrelated cells (294.9 +/- 105.4 MUm). The clonal dispersion from
      individual Tbr2 positive intermediate progenitors contributes to increasing the
      cortical surface. Our study also describes extracortical contributions from Tbr2+
      progenitors to the lateral olfactory tract and ventromedial hypothalamic nucleus.

PMID- 24927932
TI  - Roles of MAPKAPK-2 and HSP27 in the reduction of renal ischemia-reperfusion
      injury by ischemic postconditioning in rats.
AB  - PURPOSE: Ischemic postconditioning is a procedure during which intermittent
      reperfusions are performed in the early phase of reperfusion to protect organs
      from ischemia/reperfusion injury. And in this study, we mainly investigated the
      injury-alleviative role of mitogen-activated protein kinase-activating protein
      kinase-2 (MAPKAPK-2) and heat shock protein 27 (HSP27) in renal ischemic
      reperfusion injury during the procedure of ischemic postconditioning. METHODS:
      Sprague-Dawley rats were randomly divided into four groups. The injury models
      were prepared by clipping the left renal pedicle of rats after ligating the right
      renal pedicle for 60 min. In the ischemic postconditioning group, sequential
      reperfusions were done for 10 s and another ischemia for 10 s for six cycles
      after kidney ischemia for 60 min. In addition, the specific inhibitor SB203580
      was injected through caudal vein before ischemia. Serum creatinine, blood urea
      nitrogen and the expression of HSP27 and MAPKAPK-2 were detected 1, 3, 6 and 24 h
      later after reperfusion. Furthermore, phosphorylation of HSP27 and MAPKAPK-2
      protein contents, histological changes and apoptosis were compared 24 h later
      after reperfusion. RESULTS: Our data showed that ischemic postconditioning
      attenuated the renal dysfunction and cell apoptosis induced by I/R and increased
      phosphorylation of MAPKAPK-2 and HSP27. The results indicated that ischemic
      postconditioning decreased apoptosis and improved renal function. CONCLUSIONS:
      Taken together, it is suggested that the renal protective effect may be related
      to the levels of HSP27 and MAPKAPK-2 activation.

PMID- 24927933
TI  - Environmental and stressful factors affecting the occurrence of kidney stones and
      the kidney colic.
AB  - The first renal disease described from Hippocrates is nephrolithiasis with renal
      colic, which is the pain of stone passage and is also a common renal problem with
      easily recognizable characteristics. There has been much written about dietary
      factors, which have unequivocally been proved to play an important role in the
      formation of kidney stones. In this regard, it is of interest that the
      contribution of factors such as stressful events, life style, or occupation in
      the formation of kidney stones has not been well studied. This review examines
      the clinical evidence of the stressful events and other environmental factors
      affecting the occurrence of kidney stones. 

PMID- 24927934
TI  - Posterior instrumentation after a failed balloon kyphoplasty in the thoracolumbar
      junction: a case report.
AB  - INTRODUCTION: Balloon kyphoplasty provides symptomatic relief of vertebral
      compression fractures in elderly patients. Peri-operative complications are rare;
      however, they can potentially be devastating. To the best of our knowledge,
      complications during balloon kyphoplasty have not been described previously in
      published case reports. CASE PRESENTATION: A 66-year-old man who was a farmer of
      Caucasian origin presented with a 6-month history of back pain after a fall. We
      discovered a significant T12 wedge compression fracture, so we performed a T12
      balloon kyphoplasty. Approximately 2 weeks after being discharged from our
      hospital, the patient presented with increasing back pain. He presented for a
      second time with excruciating pain on the left side of his thoracolumbar region,
      so he was admitted to our ward. X-rays did not show any further fractures or
      compromise, but magnetic resonance imaging showed extensive edema in the T11 and
      L1 vertebral bodies as well as fluid tracking from the T11-T12 disc into the
      vertebral body. Nine days after being discharged, the patient presented to the
      outpatient clinic with severe back pain. Magnetic resonance imaging at that visit
      showed edema at the levels above and below the T11/T12 disc. He was put into a
      brace and given 300mg of morphine, which did not provide any pain resolution.
      Posterior instrumentation from T9 to L2 (pedicle fixation of T9-T10 as well as L1
      L2, rods in between and a crosslink above T11-T12) was performed as the final
      treatment, and the patient was discharged uneventfully. CONCLUSION: Patients
      presenting with residual pain over a previous balloon kyphoplasty level should
      raise high suspicion for a fracture or complication involving the levels above
      and/or below the balloon kyphoplasty. The best way to treat fractures that
      develop after a failed balloon kyphoplasty is to instrument and fuse posteriorly.
      Our present case report shows that a high level of suspicion for possible new
      fractures should be maintained for all similar cases.

PMID- 24927935
TI  - The identification of wadB, a new glycosyltransferase gene, confirms the branched
      structure and the role in virulence of the lipopolysaccharide core of Brucella
      abortus.
AB  - Brucellosis is a worldwide extended zoonosis caused by Brucella spp. These gram
      negative bacteria are not readily detected by innate immunity, a virulence
      related property largely linked to their surface lipopolysaccharide (LPS). The
      role of the LPS lipid A and O-polysaccharide in virulence is well known.
      Moreover, mutation of the glycosyltransferase gene wadC of Brucella abortus,
      although not affecting O-polysaccharide assembly onto the lipid-A core section
      causes a core oligosaccharide defect that increases recognition by innate
      immunity. Here, we report on a second gene (wadB) encoding a LPS core
      glycosyltransferase not involved in the assembly of the O-polysaccharide-linked
      core section. As compared to wild-type B. abortus, a wadB mutant was sensitive to
      bactericidal peptides and non-immune serum, and was attenuated in mice and
      dendritic cells. These observations show that as WadC, WadB is also involved in
      the assembly of a branch of Brucella LPS core and support the concept that this
      LPS section is a virulence-related structure.

PMID- 24927936
TI  - Cardiopathogenic mediators generated by GATA4 signaling upon co-activation with
      endothelin-1 and Trypanosoma cruzi infection.
AB  - Trypanosoma cruzi (Tc), the etiological agent of Chagas disease, triggers
      multiple responses in the myocardium, a central organ of infection and pathology
      in the host. Parasite-driven induction of diverse regulators of cardiovascular
      function, including the vasoconstrictor endothelin-1 (ET-1), the inducible form
      of nitric oxide synthase (iNOS) and the B-type natriuretic peptide (BNP), has
      been linked to the development of severe chagasic cardiomyopathy. Our current
      goal was to analyze the participation of the zinc finger transcription factor
      GATA4, critically implicated in pathological cardiac hypertrophic response, in
      the generation of key mediators involved in the pathogenesis of Tc-elicited heart
      dysfunction. In this study, we found that the combined effects of Tc and ET-1 on
      atrial myocytes promoted the protein expression, phosphorylation and DNA-binding
      activity of GATA4, leading to augmented protein levels of iNOS and increased
      nitric oxide release. Moreover, Tc- and ET-1-co-activation of cardiomyocytes
      resulted in enhanced GATA4-dependent secretion of BNP. Accordingly, mice with
      chronic chagasic cardiomyopathy showed increased expression of GATA4, iNOS and
      BNP at inflammatory lesions in cardiac muscle. Our findings support a role for
      the GATA4 signaling pathway in the myocardial production of pathogenic mediators
      associated with Chagas heart disease, and may help define novel therapeutic
      targets. 

PMID- 24927937
TI  - Acceptance of controlled drinking among treatment specialists of alcohol
      dependence in Japan.
AB  - AIMS: This study evaluated the acceptance of controlled drinking (CD) goals among
      physicians specializing in the treatment of alcohol dependence (AD) in Japan.
      METHODS: A mailed questionnaire survey was sent to physician members of the
      Japanese Society of Alcohol-Related Problems (n = 232) who were specialists in
      the treatment of AD in Japan. The evaluated items included the acceptance of CD
      goals, the definition of CD, the reasons for accepting or rejecting CD and the
      patient factors used to make treatment-goal decisions. RESULTS: CD as an interim
      goal on the way toward abstinence was accepted by about two-thirds of the
      specialists, while CD as a final goal was accepted by about one-third of
      specialists. Specialists supported harm-free drinking and a satisfactory quality
      of life, rather than alcohol consumption limits, as the definition of CD. Of
      note, a significantly higher percentage of specialists who rejected CD, compared
      with those who accepted CD, supported the disease model of AD as grounds for
      their decision. Specialists who accepted CD relied mostly on factors such as the
      severity of dependence, attitude toward CD and abstinence, and the level of
      psychological dependence and social stability, when making treatment-goal
      decisions. CONCLUSION: CD was accepted as an interim goal by two-thirds and as a
      final goal by one-third of Japanese physician specialists. Despite differences in
      drinking cultures and treatment circumstances, great similarities were found
      between this study and those conducted in Europe and North America with regard to
      the reasoning of treatment providers and the use of patient characteristics to
      make treatment-goal decisions.

PMID- 24927939
TI  - Cancer survivors face substantial financial burdens, US report says.

PMID- 24927938
TI  - Combination treatment with doxorubicin and gamitrinib synergistically augments
      anticancer activity through enhanced activation of Bim.
AB  - BACKGROUND: A common approach to cancer therapy in clinical practice is the
      combination of several drugs to boost the anticancer activity of available drugs
      while suppressing their unwanted side effects. In this regard, we examined the
      efficacy of combination treatment with the widely-used genotoxic drug doxorubicin
      and the mitochondriotoxic Hsp90 inhibitor gamitrinib to exploit disparate stress
      signaling pathways for cancer therapy. METHODS: The cytotoxicity of the drugs as
      single agents or in combination against several cancer cell types was analyzed by
      MTT assay and the synergism of the drug combination was evaluated by calculating
      the combination index. To understand the molecular mechanism of the drug
      synergism, stress signaling pathways were analyzed after drug combination. Two
      xenograft models with breast and prostate cancer cells were used to evaluate
      anticancer activity of the drug combination in vivo. Cardiotoxicity was assessed
      by tissue histology and serum creatine phosphokinase concentration. RESULTS:
      Gamitrinib sensitized various human cancer cells to doxorubicin treatment, and
      combination treatment with the two drugs synergistically increased apoptosis. The
      cytotoxicity of the drug combination involved activation and mitochondrial
      accumulation of the proapoptotic Bcl-2 family member Bim. Activation of Bim was
      associated with increased expression of the proapoptotic transcription factor
      C/EBP-homologous protein and enhanced activation of the stress kinase c-Jun N
      terminal kinase. Combined drug treatment with doxorubicin and gamitrinib
      dramatically reduced in vivo tumor growth in prostate and breast xenograft models
      without increasing cardiotoxicity. CONCLUSIONS: The drug combination showed
      synergistic anticancer activities toward various cancer cells without aggravating
      the cardiotoxic side effects of doxorubicin, suggesting that the full therapeutic
      potential of doxorubicin can be unleashed through combination with gamitrinib.

PMID- 24927940
TI  - An open-pollinated design for mapping imprinting genes in natural populations.
AB  - With the increasing recognition of its role in trait and disease development, it
      is crucial to account for genetic imprinting to illustrate the genetic
      architecture of complex traits. Genetic mapping can be innovated to test and
      estimate effects of genetic imprinting in a segregating population derived from
      experimental crosses. Here, we describe and assess a design for imprinting
      detection in natural plant populations. This design is to sample maternal plants
      at random from a natural population and collect open-pollinated (OP) seeds
      randomly from each maternal plant and germinate them into seedlings. A two-stage
      hierarchical platform is constructed to jointly analyze maternal and OP progeny
      markers. Through tracing the segregation and transmission of alleles from the
      parental to progeny generation, this platform allows parent-of-origin-dependent
      gene expression to be discerned, providing an avenue to estimate the effect of
      imprinting genes on a quantitative trait. The design is derived to estimate
      imprinting effects expressed at the haplotype level. Its usefulness and
      utilization were validated through computer simulation. This OP-based design
      provides a tool to detect the genomic distribution and pattern of imprinting
      genes as an important component of heritable variation that is neglected in
      traditional genetic studies of complex traits. 

PMID- 24927941
TI  - Acceptability of self-collection sampling for HPV-DNA testing in low-resource
      settings: a mixed methods approach.
AB  - BACKGROUND: Vaginal self-sampling with HPV-DNA tests is a promising primary
      screening method for cervical cancer. However, women's experiences, concerns and
      the acceptability of such tests in low-resource settings remain unknown. METHODS:
      In India, Nicaragua, and Uganda, a mixed-method design was used to collect data
      from surveys (N = 3,863), qualitative interviews (N = 72; 20 providers and 52
      women) and focus groups (N = 30 women) on women's and providers' experiences with
      self-sampling, women's opinions of sampling at home, and their future needs.
      RESULTS: Among surveyed women, 90% provided a self- collected sample. Of these,
      75% reported it was easy, although 52% were initially concerned about hurting
      themselves and 24% were worried about not getting a good sample. Most surveyed
      women preferred self-sampling (78%). However it was not clear if they responded
      to the privacy of self-sampling or the convenience of avoiding a pelvic
      examination, or both. In follow-up interviews, most women reported that they
      didn't mind self-sampling, but many preferred to have a provider collect the
      vaginal sample. Most women also preferred clinic-based screening (as opposed to
      home-based self-sampling), because the sample could be collected by a provider,
      women could receive treatment if needed, and the clinic was sanitary and provided
      privacy. Self-sampling acceptability was higher when providers prepared women
      through education, allowed women to examine the collection brush, and were
      present during the self-collection process. Among survey respondents, aids that
      would facilitate self-sampling in the future were: staff help (53%), additional
      images in the illustrated instructions (31%), and a chance to practice beforehand
      with a doll/model (26%). CONCLUSION: Self-and vaginal-sampling are widely
      acceptable among women in low-resource settings. Providers have a unique
      opportunity to educate and prepare women for self-sampling and be flexible in
      accommodating women's preference for self-sampling.

PMID- 24927942
TI  - A simple and efficient synthesis of fused morpholine pyrrolidines/piperdines with
      potential insecticidal activities.
AB  - A simple and efficient synthesis of fused morpholine pyrrolidine/piperdine core
      structures was accomplished via a Petasis-borono Mannich reaction of cyclic amino
      alcohols, glyoxal and arylboronic acids with moderate to good yields. The
      bioassay data showed that the synthesized compounds displayed selective
      insecticidal activities against armyworm and root-knot nematode. 

PMID- 24927943
TI  - Reinstating salience effects over time: the influence of stimulus changes on
      visual selection behavior over a sequence of eye movements.
AB  - Recently, we showed that salience affects initial saccades only in a static
      stimulus environment; subsequent saccades were unaffected by salience but,
      instead, were directed in line with task requirements (Siebold, van Zoest, &
      Donk, PLoS ONE 6(9): e23552, 2011). Yet multiple studies have shown that people
      tend to fixate salient regions more often than nonsalient ones when they are
      looking at images--in particular, when salience is defined by dynamic changes.
      The goal of the present study was to investigate how oculomotor selection beyond
      an initial saccade is affected by salience as derived from changing, as opposed
      to static, stimuli. Observers were presented with displays containing two
      fixation dots, one target, one distractor, and multiple background elements. They
      were instructed to fixate on one of the fixation dots and make a speeded eye
      movement to the target, either directly or preceded by an initial eye movement to
      the other fixation dot. In Experiment 1, target and distractor differed in
      orientation contrast relative to the background, such that one was more salient
      than the other, whereas in Experiments 2 and 3, the orientation contrast between
      the two elements was identical. Here, salience was implemented by a continuous
      luminance flicker or by a difference in luminance contrast, respectively, which
      was presented either simultaneously with display onset or contingent upon the
      first saccade. The results showed that in all experiments, initial saccades were
      strongly guided by salience, whereas second saccades were consistently goal
      directed if the salience manipulation was present from display onset. However, if
      the flicker or luminance contrast was presented contingent upon the initial
      saccade, salience effects were reinstated. We argue that salience effects are
      short-lived but can be reinstated if new information is presented, even when this
      occurs during an eye movement.

PMID- 24927944
TI  - Gaze direction and the extraction of egocentric distance.
AB  - The angular declination of a target with respect to eye level is known to be an
      important cue to egocentric distance when objects are viewed or can be assumed to
      be resting on the ground. When targets are fixated, angular declination and the
      direction of the gaze with respect to eye level have the same objective value.
      However, any situation that limits the time available to shift gaze could leave
      to-be-localized objects outside the fovea, and, in these cases, the objective
      values would differ. Nevertheless, angular declination and gaze declination are
      often conflated, and the role for retinal eccentricity in egocentric distance
      judgments is unknown. We report two experiments demonstrating that gaze
      declination is sufficient to support judgments of distance, even when
      extraretinal signals are all that are provided by the stimulus and task
      environment. Additional experiments showed no accuracy costs for extrafoveally
      viewed targets and no systematic impact of foveal or peripheral biases, although
      a drop in precision was observed for the most retinally eccentric targets. The
      results demonstrate the remarkable utility of target direction, relative to eye
      level, for judging distance (signaled by angular declination and/or gaze
      declination) and are consonant with the idea that detection of the target is
      sufficient to capitalize on the angular declination of floor-level targets
      (regardless of the direction of gaze). 

PMID- 24927945
TI  - Slope estimation and viewing distance of the observer.
AB  - The overestimation of geographical slant is one of the most sizable visual
      illusions. However, in some cases estimates of close-by slopes within the range
      of the observer's personal space have been found to be rather accurate. We
      propose that the seemingly diverse findings can be reconciled when taking the
      viewing distance of the observer into account. The latter involves the distance
      of the observer from the slope (personal space, action space, and vista space)
      and also the eye-point relative to the slope. We separated these factors and
      compared outdoor judgments to those collected with a three-dimensional (3D) model
      of natural terrain, which was within arm's reach of the observer. Slope was
      overestimated in the outdoors at viewing distances between 2 m and 138 m. The 3D
      model reproduced the errors in monocular viewing; however, performance was
      accurate with stereoscopic viewing. We conclude that accurate slant perception
      breaks down as soon as the situation exits personal space, be it physically or be
      it by closing one eye.

PMID- 24927946
TI  - The impact of immigration and visible minority status on psychosis symptom
      profile.
AB  - PURPOSE: Immigrants have heightened risks of psychotic disorders, and it is
      proposed that migration influences symptom profiles. The purpose of this study
      was to investigate if either migration experience and/or visible minority status
      affected symptom profiles, using a cross-culturally validated five-factor model
      of the Positive and Negative Syndrome Scale (PANSS), in patients with broadly
      defined psychotic disorders. METHODS: PANSS was assessed in a large catchment
      area based sample of patients with psychotic disorders verified with the
      Structured Clinical Interview for DSM-IV (n = 1,081). Symptom profiles based on
      Wallwork et al. five-factor model were compared for Norwegians (73 %), white
      immigrants (10.5 %), and visible minority groups (16.5 %). RESULTS: Visible
      minorities were significantly younger, had less education, more often a
      schizophrenia diagnosis and higher PANSS positive, negative and
      disorganized/concrete factor scores than Norwegians and white immigrants. After
      controlling for confounders only the items "Delusions" and "Difficulty in
      abstract thinking" differed between groups. Multivariate analyses indicated that
      these items were not associated with immigration per se, but rather belonging to
      a visible minority. CONCLUSION: We found mostly similarities in psychotic
      symptoms between immigrants and Norwegians when using a cross-culturally
      validated five-factor model of the PANSS. Immigration did not directly influence
      psychotic symptom profiles but visible minority groups had higher levels of
      "Delusions" and "Difficulty in abstract thinking", both symptoms that are
      partially context dependent.

PMID- 24927947
TI  - How equitable are psychological therapy services in South East London now? A
      comparison of referrals to a new psychological therapy service with participants
      in a psychiatric morbidity survey in the same London borough.
AB  - PURPOSE: Psychological therapy services are sometimes characterised as being
      small and inequitable, with an over-representation of white middle class women.
      The 'Improving Access to Psychological Therapies (IAPT)' initiative is a
      programme in England that attempts to make evidence-based therapies accessible to
      more people more equitably. The aim of this study is to assess whether an IAPT
      service is delivering an equitable service a London borough. Patients using
      services at the Southwark IAPT service (n = 4,781) were compared with a sub-group
      of participants in the South East London Community Health study (SELCOH) with
      diagnosable mental health problems and who were also resident in Southwark (n =
      196). METHODS: We compared Southwark IAPT patients and SELCOH participants on
      equity criteria of age, gender, ethnicity, occupational status and benefits
      status. To investigate if referral pathways influenced equity, patients referred
      by their general practitioner (GP pathway) (n = 3,738) or who self-referred (self
      referral pathway) (n = 482) were compared with SELCOH participants. RESULTS:
      Southwark IAPT patients significantly differed from SELCOH participants on all
      our equity criteria and similar differences were found with GP pathway patients.
      However, self-referrals did not differ from the SELCOH group on age, gender,
      ethnicity and benefit status. CONCLUSIONS: When compared to a community sample
      with diagnosable mental disorders, health disparities were found with the overall
      Southwark IAPT service and with GP pathway patients. Although unemployed people
      did access IAPT, fewer disparities were found with the self-referral pathway
      patients, suggesting that the IAPT self-referral pathway may be important in
      reducing inequitable access to services.

PMID- 24927948
TI  - Patient, psychiatrist and family carer experiences of community treatment orders:
      qualitative study.
AB  - PURPOSE: Current literature on personal experiences of community treatment orders
      (CTO) is limited. This paper examines participants' experiences of the mechanisms
      via which the CTO was designed to work: the conditions that form part of the
      order and the power of recall. We also report an emergent dimension, legal clout
      and participants' impressions of CTO effectiveness. This paper will contribute to
      a fuller picture of how the law is implemented and how CTOs operate in practice.
      METHODS: In-depth qualitative interviews were conducted with a purposive sample
      of 26 patients, 25 psychiatrists and 24 family carers about their experiences and
      views of CTOs. Data were analysed using the constant comparative method. RESULTS:
      All three sample groups perceived the chief purpose of CTOs to be medication
      enforcement and that its legal clout was central to achieving medication
      adherence. Understanding of how the inbuilt mechanisms of the CTO work varied
      considerably: participants expressed uncertainty regarding the enforceability of
      discretionary conditions and the criteria for recall. We found mixed evidence
      regarding whether recall simplified responses to relapse or risk. The range of
      experiences and views identified within each group suggests that there is no
      single definitive experience or view of CTOs. CONCLUSIONS: The (perceived) focus
      of the CTO on medication adherence combined with the variations in understanding
      within and across groups might not only have consequences for how CTOs are viewed
      and subsequently experienced, but also for broader goals in patient care and
      patient and carer involvement.

PMID- 24927951
TI  - Prevalence of portal vein thrombosis in Egyptian patients with Budd-Chiari
      syndrome.

PMID- 24927949
TI  - Genomic and phenotypic attributes of novel salinivibrios from stromatolites,
      sediment and water from a high altitude lake.
AB  - BACKGROUND: Salinivibrios are moderately halophilic bacteria found in salted
      meats, brines and hypersaline environments. We obtained three novel conspecific
      Salinivibrio strains closely related to S. costicola, from Socompa Lake, a high
      altitude hypersaline Andean lake (approx. 3,570 meters above the sea level).
      RESULTS: The three novel Salinivibrio spp. were extremely resistant to arsenic
      (up to 200 mM HAsO42-), NaCl (up to 15%), and UV-B radiation (19 KJ/m2,
      corresponding to 240 minutes of exposure) by means of phenotypic tests. Our
      subsequent draft genome ionsequencing and RAST-based genome annotation revealed
      the presence of genes related to arsenic, NaCl, and UV radiation resistance. The
      three novel Salinivibrio genomes also had the xanthorhodopsin gene cluster
      phylogenetically related to Marinobacter and Spiribacter. The genomic taxonomy
      analysis, including multilocus sequence analysis, average amino acid identity,
      and genome-to-genome distance revealed that the three novel strains belong to a
      new Salinivibrio species. CONCLUSIONS: Arsenic resistance genes, genes involved
      in DNA repair, resistance to extreme environmental conditions and the possible
      light-based energy production, may represent important attributes of the novel
      salinivibrios, allowing these microbes to thrive in the Socompa Lake.

PMID- 24927950
TI  - Acid-fast bacilli culture positivity and drug resistance in abdominal
      tuberculosis in Mumbai, India.
AB  - BACKGROUND AND AIM: Culture positivity for Mycobacterium tuberculosis complex
      (MTB) in abdominal tuberculosis (TB) using Lowenstein Jensen medium and Bactec
      system varies from 25 % to 36 %. Data on the prevalence of drug resistance in
      primary abdominal TB is scant. Our aim was to study the acid-fast bacilli (AFB)
      culture positivity rate in primary abdominal TB using Bactec Mycobacterial Growth
      Indicator Tubes (MGIT) system and the prevalence of drug resistance in these
      patients. METHOD: Records of patients with abdominal TB (diagnosed on clinical
      features, endoscopy, histology, microbiology) seen during the period 2008 to 2013
      were retrieved from the Gastroenterology and Microbiology departments. Patients
      with extra-abdominal TB (five pulmonary, two nodal), adnexal (one), and HIV (one)
      were excluded from analysis. RESULTS: Of 61 patients, 31 (50.8 %) had a positive
      AFB culture. In the 30 culture-negative patients, histology showed non-caseating
      granulomas in 25 patients. Drug sensitivity pattern was analyzed in 18 patients;
      resistance was detected in eight (14.3 % of all patients and 44.4 % of patients
      in whom drug sensitivity was done) including three (5.4 % of all subjects and
      16.6 % in whom drug sensitivity was available) who were multidrug-resistant.
      CONCLUSIONS: The rate of AFB culture positivity in primary abdominal TB was 50.8
      % using Bactec MGIT. Likelihood of drug resistance was seen in 14.3 %, of whom
      5.4 % were multidrug-resistant.

PMID- 24927952
TI  - Spectrum of small bowel perforation in a tertiary care hospital of south India:
      predictors of morbidity and mortality.

PMID- 24927953
TI  - Use of oral gadobenate dimeglumine to visualise the oesophagus during magnetic
      resonance angiography in patients with atrial fibrillation prior to catheter
      ablation.
AB  - BACKGROUND: Atrio-oesophageal fistula was first reported as a fatal complication
      of surgical endocardial and percutaneous endocardial radiofrequency ablation for
      atrial fibrillation, with an incidence after catheter ablation between 0.03% and
      0.5%. Magnetic resonance angiography (MRA) was usually performed to obtain pre
      procedural 3D images, used to merging into an electro-anatomical map, guiding
      step-by-step ablation strategy of AF. Our aim was to find an easy, safe and cost
      effective way to enhance the oesophagus during MRA. METHODS: In 105 consecutive
      patients, a right-left phase encoding, free breathing, 3D T1 MRA sequence was
      performed in the axial plane, >24 hours before catheter ablation, using an
      intravenous injection of gadobenate dimeglumine contrast medium. The oesophagus
      was enhanced using an oral gel solution of 0.7 mL gadobenate dimeglumine contrast
      medium mixed with approximately 40 mg thickened water gel, which was swallowed by
      the patients on the scanning table, immediately before the MRA sequence
      acquisition. RESULTS: The visualisation of the oesophagus was obtained in 104/105
      patients and images were successfully merged, as left atrium and pulmonary veins,
      into an electro-anatomical map, during percutaneous endocardial radiofrequency
      ablation. All patients tolerated the study protocol and no immediate or late
      complication was observed with the oral contrast agent administration. The free
      breathing MRA sequence used in our protocol took 7 seconds longer than MRA breath
      hold conventional sequence. CONCLUSION: Oesophagus visualization with oral
      gadobenate dimeglumine is feasible for integration of oesophagus anatomy images
      into the electro-anatomical map during AF ablation, without undesirable side
      effects and without significantly increasing cost or examination time.

PMID- 24927954
TI  - Predictors of burnout: results from a prospective community study.
AB  - The possible link between work strain and subsequent mental disorders has
      attracted public attention in many European countries. Burnout has become a
      favored concept within this context. Most burnout research has concentrated on
      various professional groups and less so on ordinary community samples. We
      analyzed the data collected from a 30-year community sample during seven
      measuring occasions, beginning in 1978. In the last assessment (2008), we
      included for the first time the Maslach Burnout Inventory (MBI). Making the
      diagnosis of a lifetime mental disorder a predictor for burnout required us to
      compile the cumulative prevalence rate over all seven occasions. We also
      evaluated various psycho-social predictors of burnout over the life cycle of our
      sample. Concurrent associations of the MBI with subscales from the SCL-90-R were
      also investigated. The relationship of burnout with several SCL-90-R subscales
      demonstrated that, in all dimensions, burnout is associated with significant
      psychopathology. Persons with a lifetime mood disorder, and especially those with
      a combination of mood and anxiety disorders, had a higher risk for subsequent
      burnout. Various partnership problems were another predictor for burnout. In
      conclusion, the role of mental disorder as an occupational illness remains
      controversial. Various forms of such disorders as well as some psycho-social
      predictors can predispose to burnout. By contrast, work-related predictors appear
      to be less important. 

PMID- 24927955
TI  - Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate
      concentrations in Chinese children with acute lymphoblastic leukemia.
AB  - MicroRNAs (miRNAs) are a class of short non-coding RNA that can specially bind to
      the 3'-untranslated region of target mRNAs and regulate gene expression at the
      posttranscriptional level. This study investigated the effects of a miRNA binding
      site polymorphism (rs1051296) in solute carrier family 19, member 1 (SLC19A1) on
      serum methotrexate (MTX) concentrations in Chinese children with acute
      lymphoblastic leukemia (ALL). Genotyping for SLC19A1 rs1051296 G>T in 131
      children with ALL was performed using the Sequenom MassArray system. A total of
      131 patients received high-dose MTX treatment, and serum MTX concentrations were
      measured by a fluorescence polarization immunoassay 24 (MTX C24h) and 42 h (MTX
      C42h) after administration. The frequency of the rs1051296 T allele observed in
      this study (46.2 %) was significantly lower than that previously observed in a
      European population (60.7 %, P = 0.002). There was significant association
      between rs1051296 G>T and MTX C24h (29.97, 32.34, and 39.01 umol/L for GG, GT,
      and TT genotypes, respectively, P = 0.04). The percentage of patients with an MTX
      concentration above the therapeutic threshold (40 MUmol/L) was significantly
      lower in GG carriers compared with that in GT and TT carriers (8.6 % for GG
      genotype vs. 26.8 and 40.0 % for CT and TT genotypes, respectively, P = 0.02).
      Delayed elimination of MTX (C42h > 1 MUmol/L) was less frequent in GG carriers
      than in GT and TT carriers. Rs1051296 G>T was associated with MTX plasma
      concentration, suggesting that miRNAs might be involved in the post
      transcriptional regulation of SLC19A1.

PMID- 24927956
TI  - Value of neutrophil lymphocyte ratio in patients with hepatocellular carcinoma
      undergoing TAE combined with Sorafenib.

PMID- 24927957
TI  - Prognostic impact of circulating monocytes and lymphocyte-to-monocyte ratio on
      previously untreated metastatic non-small cell lung cancer patients receiving
      platinum-based doublet.
AB  - The link between circulating lymphocyte-to-monocyte ratio (LMR) and newly
      diagnosed metastatic non-small cell lung cancer (NSCLC) is not fully defined. The
      study was conducted to evaluate the prognostic impact of LMR on survival outcomes
      in previously untreated metastatic NSCLC patients receiving platinum-based
      doublet. Chemotherapy-naive metastatic NSCLC patients undergoing platinum-based
      doublet were retrospectively enrolled. Clinical features regarding gender, age,
      Eastern Cooperative Oncology Group (ECOG) performance status, histology, absolute
      lymphocyte count (ALC), absolute monocyte count (AMC) and LMR were collected to
      determinate their prognostic impact on progression-free survival (PFS) and
      overall survival (OS). Up to 370 patients were eligible for the study. By
      univariate analysis, ECOG performance status, histology, ALC, AMC and LMR were
      showed to be significantly associated with PFS and OS. In subsequent Cox
      multivariate analysis, non-squamous cell carcinoma, ALC >= 2.45 * 10(9)/L, AMC
      <0.45 * 10(9)/L and LMR >= 4.56 were demonstrated to be independently correlated
      with better PFS. In addition, independent favorable prognostic factors for OS
      were only limited to LMR >= 4.56 and non-squamous cell carcinoma, whereas ECOG
      performance status of 2 and AMC >= 0.45 * 10(9)/L remained as independently
      inferior prognostic indicators for OS. Our findings implicate that circulating
      AMC and LMR are regarded as independent prognostic factors for PFS and OS in
      previously untreated metastatic NSCLC patients receiving platinum-based doublet.

PMID- 24927958
TI  - What factors determine Belgian general practitioners' approaches to detecting and
      managing substance abuse? A qualitative study based on the I-Change Model.
AB  - BACKGROUND: General practitioners (GPs) are considered to play a major role in
      detecting and managing substance abuse. However, little is known about how or why
      they decide to manage it. This study investigated the factors that influence GP
      behaviours with regard to the abuse of alcohol, illegal drugs, hypnotics, and
      tranquilisers among working Belgians. METHODS: Twenty Belgian GPs were
      interviewed. De Vries' Integrated Change Model was used to guide the interviews
      and qualitative data analyses. RESULTS: GPs perceived higher levels of substance
      abuse in urban locations and among lower socioeconomic groups. Guidelines, if
      they existed, were primarily used in Flanders. Specific training was unevenly
      applied but considered useful. GPs who accepted abuse management cited strong
      interpersonal skills and available multidisciplinary networks as facilitators.GPs
      relied on their clinical common sense to detect abuse or initiate management.
      Specific patients' situations and their social, psychological, or professional
      dysfunctions were cited as cues to action.GPs were strongly influenced by their
      personal representations of abuse, which included the balance between their
      professional responsibilities toward their patients and the patients'
      responsibilities in managing their own health as well the GPs' abilities to cope
      with unsatisfying patient outcomes without reaching professional exhaustion. GPs
      perceived substance abuse along a continuum ranging from a chronic disease (whose
      management was part of their responsibility) to a moral failing of untrustworthy
      people. Alcohol and cannabis were more socially acceptable than other drugs.
      Personal experiences of emotional burdens (including those regarding substance
      abuse) increased feelings of empathy or rejection toward
      patients.Multidisciplinary practices and professional experiences were cited as
      important factors with regard to engaging GPs in substance abuse management. Time
      constraints and personal investments were cited as important
      barriers.Satisfaction with treatment was rare. CONCLUSIONS: Motivational factors,
      including subjective beliefs not supported by the literature, were central in
      deciding whether to manage cases of substance abuse. A lack of theoretical
      knowledge and training were secondary to personal attitudes and motivation.
      Personal development, emotional health, self-awareness, and self-care should be
      taught to and fostered among GPs to help them maintain a patient-centred focus.
      Health authorities should support collaborative care.

PMID- 24927959
TI  - Control of Japanese encephalitis in Asia: the time is now.
AB  - Japanese encephalitis (JE) virus is the most common vaccine-preventable cause of
      encephalitis in Asia. Recent progress in the development and availability of
      improved JE vaccines has revitalized the prospects for JE control. There now are
      a number of safe and effective vaccines, two WHO prequalified vaccines available
      for pediatric use, at least one vaccine considered affordable for use in lower
      income countries, and a GAVI Alliance commitment to provide financial support to
      eligible countries for campaigns for children aged 9 months through 14 years.
      While challenges remain, this tremendous progress means there is a better
      opportunity than at any time in the past to prevent the substantial morbidity and
      mortality from this disease. 

PMID- 24927960
TI  - Diabetic cardiomyopathy is associated with defective myocellular copper
      regulation and both defects are rectified by divalent copper chelation.
AB  - BACKGROUND: Heart disease is the leading cause of death in diabetic patients, and
      defective copper metabolism may play important roles in the pathogenesis of
      diabetic cardiomyopathy (DCM). The present study sought to determine how
      myocardial copper status and key copper-proteins might become impaired by
      diabetes, and how they respond to treatment with the Cu (II)-selective chelator
      triethylenetetramine (TETA) in DCM. METHODS: Experiments were performed in Wistar
      rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment.
      Cardiac function was analyzed in isolated-perfused working hearts, and myocardial
      total copper content measured by particle-induced x-ray emission spectroscopy
      (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative
      expression (mRNA and protein) and/or activity of key proteins that mediate LV
      tissue-copper binding and transport, were analyzed by combined RT-qPCR, western
      blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical
      analysis was performed using Student's t-tests or ANOVA and p-values of < 0.05
      have been considered significant. RESULTS: Left-ventricular (LV) copper levels
      and function were severely depressed in rats following 16-weeks' diabetes, but
      both were unexpectedly normalized 8-weeks after treatment with TETA was
      instituted. Localized myocardial copper deficiency was accompanied by decreased
      expression and increased polymerization of the copper-responsive transition-metal
      binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant
      defences and elevated susceptibility to pro-oxidant stress. Levels of the high
      affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with
      impaired membrane copper uptake, and were not modified by TETA which,
      contrastingly, renormalized myocardial copper and increased levels and cell
      membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes
      also lowered indexes of intracellular (IC) copper delivery via the copper
      chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide
      dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which
      normalized SOD1 activity with consequent bolstering of anti-oxidant defenses.
      Furthermore, diabetes depressed levels of additional intracellular copper
      transporting proteins, including antioxidant-protein-1 (ATOX1) and copper
      transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1
      (ATP7A). CONCLUSIONS: Myocardial copper deficiency and defective cellular copper
      transport/trafficking are revealed as key molecular defects underlying LV
      impairment in diabetes, and TETA-mediated restoration of copper regulation
      provides a potential new class of therapeutic molecules for DCM.

PMID- 24927962
TI  - rTRM-web: a web tool for predicting transcriptional regulatory modules for ChIP
      seq-ed transcription factors.
AB  - Transcription factors (TFs) bind to specific DNA regions, although their binding
      specificities cannot account for their cell type-specific functions. It has been
      shown in well-studied systems that TFs combine with co-factors into
      transcriptional regulatory modules (TRMs), which endow them with cell type
      specific functions and additional modes of regulation. Therefore, the prediction
      of TRMs can provide fundamental mechanistic insights, especially when
      experimental data are limiting or when no regulatory proteins have been
      identified. Our method rTRM predicts TRMs by integrating genomic information from
      TF ChIP-seq data, cell type-specific gene expression and protein-protein
      interaction data. Here we present a freely available web interface to rTRM
      (http://www.rTRM.org/) supporting all the options originally described for rTRM
      while featuring flexible display and network calculation parameters, publication
      quality figures as well as annotated information on the list of genes
      constituting the TRM. 

PMID- 24927963
TI  - The 10-year trend of periprocedural complication following carotid artery
      stenting; single center experience.
AB  - PURPOSE: Carotid endarterectomy and stenting are used to treat carotid stenosis,
      with the volume of carotid artery procedures increasing over the past decade. We
      investigated the 10-year trend of periprocedural complications with an increasing
      procedure volume of carotid stenting at a single tertiary hospital. METHODS: We
      collected 416 consecutive cases (384 patients) of carotid artery stenting
      performed for either symptomatic (231 cases, 55.5 %) or asymptomatic (185 cases,
      44.5 %) internal carotid artery stenosis at a single center. Periprocedural
      complication was defined as any stroke, myocardial infarction, or death.
      Procedure-related outcome included any dissection, hemodynamic event, or
      periprocedural complication. RESULTS: The mean age was 68.8 years (82.8 % males;
      range of 20-89 years); 23.9 % were older than 75 years. Before the procedure,
      99.3 and 56.0 % of patients received antiplatelet and lipid-lowering medication,
      respectively. The overall periprocedural complication rate was 3.6 % (1.6 and 5.2
      % in the asymptomatic and symptomatic group, respectively). The composite outcome
      of any stroke or death was 3.4 %. Periprocedural complication and procedure
      related outcome showed a decremental trend with increasing procedure volume, and
      this trend remained after adjusting for confounders. CONCLUSIONS: Our study
      suggests that carotid stenting at an experienced center might reduce the
      periprocedural complications. Our periprocedural complication rate of carotid
      artery stenting may be comparable to, or somewhat lower than, that reported in
      other clinical trials.

PMID- 24927961
TI  - Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong
      diabetes registry.
AB  - BACKGROUND: In patients with type 2 diabetes, chronic kidney disease (CKD) is
      associated with increased risk of hypoglycaemia and death. Yet, it remains
      uncertain whether hypoglycaemia-associated mortality is modified by CKD. METHODS:
      Type 2 diabetic patients, with or without CKD at enrolment were observed between
      1995 and 2007, and followed up till 2009 at hospital medical clinics. We used
      additive interaction, estimated by relative excess risk due to interaction (RERI)
      and attributable proportion due to interaction (AP) to examine possible
      synergistic effects between CKD and severe hypoglycaemia (defined as
      hospitalisations due to hypoglycaemia in the 12 months prior to enrolment) on the
      risk of death. RESULTS: In this cohort of 8,767 type 2 diabetic patients [median
      age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11)
      years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of
      6.66 years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had
      severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15
      patients had both). In multivariable analysis and using patients without severe
      hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients),
      severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in
      781 patients) were associated with increased risk of death [Hazard ratio, HR:
      1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk
      factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91
      (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p
      values < 0.05). CONCLUSIONS: Severe hypoglycaemia and CKD interact to increase
      risk of death in type 2 diabetes patients.

PMID- 24927964
TI  - Intrahepatic flow redistribution in patients treated with radioembolization.
AB  - INTRODUCTION: In planning Yttrium-90 ((90)Y)-radioembolizations, strategy
      problems arise in tumours with multiple arterial supplies. We aim to demonstrate
      that tumours can be treated via one main feeding artery achieving flow
      redistribution by embolizing accessory vessels. METHODS: One hundred (90)Y
      radioembolizations were performed on 90 patients using glass microspheres. In 19
      lesions/17 patients, accessory branches were found feeding a minor tumour portion
      and embolized. In all 17 patients, the assessment of the complete perfusion was
      obtained by angiography and single photon emission computerized tomography
      computerized tomography (SPECT-CT). Dosimetry, toxicity, and tumor response rate
      of the patients treated after flow redistribution were compared with the 83
      standard-treated patients. Seventeen lesions in 15 patients with flow
      redistribution were chosen as target lesions and evaluated according to mRECIST
      criteria. RESULTS: In all patients, the complete tumor perfusion was assessed
      immediately before radioembolization by angiography in all patients and after the
      (90)Y-infusion by SPECT-CT in 15 of 17 patients. In the 15 assessable patients,
      the response rate in their 17 lesions was 3 CR, 8 PR, and 6 SD. Dosimetric and
      toxicity data, as well tumour response rate, were comparable with the 83 patients
      with regular vasculature. CONCLUSIONS: All embolization procedures were performed
      successfully with no complications, and the flow redistribution was obtained in
      all cases. Results in term of toxicity, median dose administered, and
      radiological response were comparable with standard radioembolizations. Our
      findings confirmed the intratumoral flow redistribution after embolizing the
      accessory arteries, which makes it possible to treat the tumour through its
      single main feeding artery.

PMID- 24927965
TI  - Comment to: update with level 1 studies of the European Hernia Society guidelines
      on the treatment of inguinal hernia in adult patients, Miserez M et al. DOI
      10.1007/s10029-014-1236-6.

PMID- 24927966
TI  - Preperitoneal femoral hernioplasty: an "umbrella" technique.
AB  - INTRODUCTION: Tension-free inguinal mesh-plug hernioplasty is well established.
      However, femoral hernia repair remains challenging and controversial. We aimed to
      evaluate a preperitoneal approach of tension-free hernioplasty for femoral hernia
      upon the anatomy rationality. METHODS: A prospective study of 62 patients between
      October 1999 and June 2011 received femoral hernioplasty in our hospital. This
      repair method involved a preperitoneal approach accomplished under regional or
      local anesthesia with mesh and plug; the emphasis was put on fulfilling the
      abdominal defect, i.e., the myopectineal orifice, with the plug flattened like an
      "umbrella", above the femoral ring but not to fill the femoral ring. RESULTS: All
      cases receiving preperitoneal tension-free hernioplasty had a smooth recovery.
      There were no severe complications, and no recurrences were detected within a 0.5
      to 4-year follow-up. No specific restrictions with regard to activity were
      placed on the patients after surgery. All cases were able to return to normal
      life, including work, within 2 weeks. CONCLUSIONS: The preperitoneal tension-free
      hernioplasty may be a more effective method of femoral hernia repair; meanwhile,
      we must re-understand the anatomy of femoral hernia correctly so as to restore
      the anatomic and physiologic functions at this region optimally.

PMID- 24927968
TI  - Prenatal hydronephrosis: postnatal evaluation and management.
AB  - Congenital hydronephrosis is one of the most common anomalies identified on
      antenatal ultrasound. The underlying etiology of congenital hydronephrosis is
      multifold, ranging from transient hydronephrosis in utero to clinically
      significant congenital anomalies of the kidney and urinary tract. While
      traditional management of hydronephrosis was aimed at relieving symptoms, the
      advent of routine prenatal ultrasound has led to a shift in the goal of treatment
      to prevention of renal injury in the asymptomatic patient. However, despite this
      focus on renal preservation, the diagnostic criteria for identification of
      children "at risk" for renal damage that can be alleviated by surgical treatment
      remain a subject of debate. Both antenatal and postnatal imaging studies have
      been evaluated as indicators for potential reversible renal damage and have been
      used as potential indicators of the need for surgical intervention. The aim of
      this review is to discuss the current literature regarding the role of postnatal
      clinical and radiographic evaluation to identify children who may benefit from
      early surgical intervention. 

PMID- 24927969
TI  - Effect of renin-angiotensin system inhibitors on long-term survival in patients
      treated with beta blockers and antiplatelet agents after acute myocardial
      infarction (from the MONICA/KORA Myocardial Infarction Registry).
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor
      blockers (ARBs) have shown to decrease mortality and cardiovascular morbidity
      especially in high-risk patients after acute myocardial infarction (AMI). Aim of
      this study was to assess the association between ACEI or ARB treatment (ACEI/ARB)
      at hospital discharge and long-term survival after AMI in real-life patient care.
      From a German population-based AMI registry, 3,544 patients (75.4% men), aged 28
      to 74 years, hospitalized with an incident AMI between 2000 and 2008, surviving
      at least 24 hours and treated with beta blockers and antiplatelet agents at
      discharge were included in this study. All data were collected by standardized
      interviews and chart review. End point of this study was all-cause mortality at 3
      follow-up periods: 1, 3, and 5 years after AMI. Mortality was assessed for all
      registered patients in 2010. Survival analyses and multivariable Cox regression
      analyses were conducted. Of the 3,544 patients, 83.7% received ACEI/ARB and 90.1%
      were treated with statins at hospital discharge. During a median follow-up period
      of 5.0 years (interquartile range 1.0 years), 9.3% patients died. In the
      multivariable Cox models adjusting for a number of covariates, use of ACEI/ARB
      showed a significantly inverse relation with 1-, 3-, and 5-year mortality (e.g.,
      5-year mortality: hazard ratio 0.74, 95% confidence interval 0.59 to 0.94, p =
      0.015), and the hazard ratios for mortality did not differ significantly between
      the 3 examined follow-up periods. In conclusion, use of ACEI/ARB at hospital
      discharge is independently associated with long-term survival benefit in patients
      with incident AMI already treated with other guideline-recommended cardiovascular
      drugs. 

PMID- 24927971
TI  - Long-term survival with revascularization in South Asians admitted with an acute
      coronary syndrome (from the Alberta Provincial Project for Outcomes Assessment in
      Coronary Heart Disease Registry).
AB  - People of South Asian (SA) descent are particularly susceptible to acute coronary
      syndromes (ACS). Yet, little information exists regarding their overall
      prognosis. The purpose of this study was to compare short- and long-term clinical
      outcomes of SA and European Canadians admitted with an ACS. Using the Alberta
      Provincial Project for Outcomes Assessment in Coronary Heart Disease registry,
      63,393 patients with ACS were reviewed (January 1999 to March 2012). After
      excluding Chinese patients, 1,825 SAs were compared with 60,791 European
      Canadians. Both groups were propensity matched, and outcomes were compared.
      Adjustment was performed using a 3:1 propensity matching technique. Adjusted 30
      day and 1-year mortality rates were similar between SA and European patients with
      ACS (2.6% vs 2.7%, p = 0.93; 5.0% vs 4.8%, respectively, p = 0.75). Repeat
      angiography did not differ (9.9% vs 9.2%, p = 0.35), yet repeat revascularization
      within 1 year was greater in SA patients (9.8% vs 7.6%, p <0.01). Improved long
      term survival (median 64 months, interquartile range 66 months) was noted with SA
      patients (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.71 to 0.95). In
      particular, long-term survival was observed in SA patients receiving coronary
      artery bypass grafting (HR 0.75, 95% CI 0.52 to 1.08) and percutaneous coronary
      intervention (HR 0.75, 95% CI 0.59 to 0.96). In conclusion, SA patients treated
      with revascularization appear to have improved long-term survival after ACS,
      compared with European Canadians. As such, clinicians should be cognitive of
      ethnic-based outcomes when determining therapeutic strategies in patient
      management. 

PMID- 24927970
TI  - Impact of trimetazidine on incidence of myocardial injury and contrast-induced
      nephropathy in diabetic patients with renal dysfunction undergoing elective
      percutaneous coronary intervention.
AB  - Trimetazidine is an anti-ischemic agent with antioxidant activity. This study
      evaluated the effect of periprocedural administration of trimetazidine on the
      incidence of percutaneous coronary intervention (PCI)-induced myocardial injury
      and contrast-induced nephropathy (CIN) in diabetic patients with mild-to-moderate
      renal dysfunction. One hundred patients with a mean glomerular filtration rate of
      48 +/- 16 (ml/min/1.73 m(2)) were prospectively enrolled, then randomly assigned
      to receive (50 patients; trimetazidine group) or not receive (50 patients;
      control group) periprocedural trimetazidine (70 mg/day) for 72 hours. The serum
      creatinine level was measured pre-PCI, 72 hours, and 10 days thereafter. An
      increase in the serum creatinine level by >0.5 mg/dl or 0.25% of the baseline
      value is considered as CIN. Cardiac troponin I levels were measured before and 6,
      12, and 24 hours after PCI. Mean age of the study cohort was 59 +/- 6 years (men
      68%). The serum creatinine level in the control group increased significantly 3
      days after PCI and decreased on the tenth day. However, it showed no significant
      change in the trimetazidine group. Incidence of CIN was 12% in the trimetazidine
      group and 28% in the control group (p <0.05). Cardiac troponin I levels were
      significantly reduced in the trimetazidine group (6 hours: 8 +/- 0.3 vs 16 +/-
      0.2 pg/ml, 12 hours: 13 +/- 0.9 vs 24 +/- 0.8 pg/ml, 24 hours: 7 +/- 0.7 vs 14 +/
      0.3 pg/ml, p <0.001). In conclusion, trimetazidine intake before elective PCI in
      diabetic patients with mild-to-moderate renal dysfunction is associated with
      decreased incidence of CIN and myocardial injury. 

PMID- 24927972
TI  - In-hospital complications associated with reoperations of implantable
      cardioverter defibrillators.
AB  - Repeat implantable cardioverter defibrillator (ICD) procedures are increasing and
      may be associated with higher risks for complications. To provide more
      information for clinical decision making, especially in light of recent
      defibrillator advisories, we examined a large national cohort to characterize
      repeat ICD procedural outcomes. Using data from the National Cardiovascular Data
      Registry (ICD Registry), we compared patient characteristics, reasons for ICD
      implantation, and associated in-hospital adverse events among 92,751 patients
      receiving their first device and 81,748 patients who underwent repeat procedures
      with (n = 31,057) and without (n = 50,691) lead involvement. Hierarchical
      multivariable logistic regression was used to determine the predictors of in
      hospital complications. Complication rates were higher in those who underwent
      repeat ICD procedures with lead involvement (lead implantation or revision),
      compared with patients who underwent initial implants (3.2% vs 2.6%, p <0.001) or
      versus those with pocket-only (e.g., generator change only) procedures (3.2% vs
      0.6%, p <0.001). There were significantly more in-hospital deaths, lead
      dislodgements, and infections requiring antibiotics in the lead involvement
      cohort. Compared with those who had a pocket-only procedure, the multivariable
      adjusted odds ratio of any complication were increased at 4.20 (95% confidence
      interval: 3.66 to 4.82, p <0.001) in patients who underwent repeat procedures
      with lead involvement excluding lead extraction or 7.11 (95% confidence interval:
      5.96 to 8.48, p <0.001) in procedures involving lead extractions. In conclusion,
      repeat ICD procedures, when involving the addition or revision of a lead with or
      without concurrent lead extraction, are associated with higher complication rates
      compared with initial implants and with those who underwent pocket-only
      procedures. 

PMID- 24927973
TI  - Relation of contrast-induced nephropathy to long-term mortality after
      percutaneous coronary intervention.
AB  - There is little information on the effect of contrast-induced nephropathy (CIN)
      on long-term mortality after percutaneous coronary intervention in patients with
      or without chronic kidney disease (CKD). Of 4,371 patients who had paired serum
      creatinine (SCr) measurements before and after percutaneous coronary intervention
      and were discharged alive in the Coronary REvascularization Demonstrating Outcome
      Study in Kyoto registry, the incidence of CIN (an increase in SCr of >=0.5 mg/dl
      from the baseline) was 5% in our study cohort. The rate of CIN in patients with
      CKD was 11%, although it was 2% without CKD (p <0.0001). During a median follow
      up of 42.3 months after discharge, 374 patients (8.6%) died. After adjustment for
      prespecified confounders, CIN was significantly correlated with long-term
      mortality in the entire cohort (hazard ratio [HR] 2.26, 95% confidence interval
      [CI] 1.62 to 2.29, p <0.0001) and in patients with CKD (HR 2.62, 95% CI 1.91 to
      3.57, p <0.0001) but not in patients without CKD (HR 1.23, 95% CI 0.47 to 2.62, p
      = 0.6). Sensitivity analyses confirmed these results using the criteria defined
      as elevations of the SCr by >=25% and 0.3 mg/dl from the baseline, respectively.
      In conclusion, CIN was significantly correlated with long-term mortality in
      patients with CKD but not in those without CKD. 

PMID- 24927974
TI  - The positive inside rule is stronger when followed by a transmembrane helix.
AB  - The translocon recognizes transmembrane helices with sufficient level of
      hydrophobicity and inserts them into the membrane. However, sometimes less
      hydrophobic helices are also recognized. Positive inside rule, orientational
      preferences of and specific interactions with neighboring helices have been shown
      to aid in the recognition of these helices, at least in artificial systems. To
      better understand how the translocon inserts marginally hydrophobic helices, we
      studied three naturally occurring marginally hydrophobic helices, which were
      previously shown to require the subsequent helix for efficient translocon
      recognition. We find no evidence for specific interactions when we scan all
      residues in the subsequent helices. Instead, we identify arginines located at the
      N-terminal part of the subsequent helices that are crucial for the recognition of
      the marginally hydrophobic transmembrane helices, indicating that the positive
      inside rule is important. However, in two of the constructs, these arginines do
      not aid in the recognition without the rest of the subsequent helix; that is, the
      positive inside rule alone is not sufficient. Instead, the improved recognition
      of marginally hydrophobic helices can here be explained as follows: the positive
      inside rule provides an orientational preference of the subsequent helix, which
      in turn allows the marginally hydrophobic helix to be inserted; that is, the
      effect of the positive inside rule is stronger if positively charged residues are
      followed by a transmembrane helix. Such a mechanism obviously cannot aid C
      terminal helices, and consequently, we find that the terminal helices in multi
      spanning membrane proteins are more hydrophobic than internal helices. 

PMID- 24927975
TI  - Pattern of drug overdose and chemical poisoning among patients attending an
      emergency department, western Saudi Arabia.
AB  - Poisoning is a medical emergency that represent a major health problem all over
      the world. Studies on drug overdose and chemical poisoning are very limited in
      Saudi Arabia (SA). We aimed to describe the current pattern and assess risk
      factors of drug overdose and chemical poisoning in King Khalid National Guard
      hospital, Jeddah, SA. Medical records of patients attended emergency department
      in King Khalid National Guard hospital during the period from January 2008 to
      December 2012 due to drug overdose and chemical poisoning were reviewed. A total
      of 129 cases were included in the study. The majority of the population was Saudi
      (97.7 %), and almost half of them were females (54.3 %). Children under 12 years
      were the most affected age group (44.2 %). Drug overdose was the most common
      cause of poisoning (92.2 %). Analgesics and non-steroidal anti-inflammatory drugs
      represented the highest percentage of used medications (20.4 %). The most
      commonly reported symptoms were symptoms of the central nervous system (57.4 %)
      followed by GIT symptoms (41.9 %). Intentional poisoning was reported in 34 cases
      (26.4 %). Female patients were significantly more likely to attempt suicide than
      male patients (OR = 7.22, 95 % CI = 1.70, 30.62). Children continue to be at high
      risk for medication and chemical poisoning. Accessibility to medications at homes
      encountered for most of poisoning cases among children. Implementing methods to
      raise public awareness and minimize children access to medications would
      significantly contribute to reducing burden of this problem on the community.

PMID- 24927976
TI  - Physicians' tobacco intervention counseling in a tertiary care hospital of South
      India.
AB  - The tobacco epidemic is one of the biggest public health threats in the present
      world with a substantial contribution to mortality and morbidity. Patients'
      visits to their doctors for illnesses and health check-ups offer a great
      opportunity to screen them for tobacco use and also counsel them to quit tobacco
      use. This cross sectional study was carried out in out-patient departments of
      General Medicine and Pulmonary Medicine of a tertiary care medical college
      teaching hospital in Dakshina Kannada district of Karnataka state of India
      between April 2012 and July 2012 among the patients aged 18 years or above who
      were diagnosed as suffering from tobacco related diseases. Exit interview was
      conducted on the patients after obtaining a written informed consent using a pre
      designed semi-structured questionnaire. Data was entered, analyzed using SPSS v17
      and Descriptive statistics, Fisher Exact test, Bivariate and multivariable
      logistic regression analyses were used. The present study reveals that 305 (87.1
      %), 281 (80.3 %) and 257 (73.1 %) of the 350 participants were asked, assessed
      and advised respectively by the treating physicians to quit tobacco use where as
      only 18 (15.1 %) were assisted in their efforts to quit tobacco. Physician's
      counseling inventions were significantly associated with patient's age, sex,
      education, marital status and socio economic status of the patients as well as
      the treating physician's experience of more than 3 years. There is a need to
      incorporate tobacco history taking as a vital sign during medical history taking
      and this should be made as a routine in medical schools.

PMID- 24927977
TI  - An outbreak of pertussis in rural Texas: an example of the resurgence of the
      disease in the United States.
AB  - During 2012, an increase in the number of pertussis cases or outbreaks was
      reported among most states within the United States. The majority of these cases
      included previously vaccinated children between the ages of 7-10 years. This
      underscores the growing concern regarding current immunization practices and
      vaccine efficacy, especially as it pertains to pertussis prevention within this
      age group. In the fall of 2012, an outbreak of pertussis occurred within a school
      district in a rural Texas county that was reflective of this national pattern.
      Our objective is to describe this outbreak, highlight the similarities with the
      national trend, and identify strategies for better disease prevention. The cases
      in this outbreak were interviewed and laboratory testing done. Information
      regarding exposure and immunization history among cases was obtained.
      Immunization audits of the affected institutions were also conducted. We
      performed a descriptive analysis of the collected data using EPI-INFO software
      v.3.5.3. A total of 34 cases were identified in this outbreak, of which 23 were
      PCR confirmed and 11 were epidemiologically linked. Ages ranged from 5 months to
      12 years, and 62 % were among children aged 7-10 years. All cases were up-to-date
      on their pertussis vaccinations. Immunization coverage rate was over 90 % within
      each of the affected institutions. The characteristics of this outbreak bear
      striking similarities to the current national trend in terms of age groups and
      immunization status of the affected cases. Increased focus on this vulnerable
      target group, including heightened scrutiny of vaccine efficacy and delivery, is
      indicated.

PMID- 24927978
TI  - Secondary traumatic stress among emergency nurses: a cross-sectional study.
AB  - Emergency department nurses are required to deal with emotional trauma issues on
      a daily basis, which may result in them experiencing symptoms of secondary
      traumatic stress, a consequence of stress experienced when helping or wanting to
      help a person traumatised or suffering. This study measured emergency department
      nurses' self-reported levels of secondary traumatic stress. Registered nurses (n
      = 117) working at three emergency departments in the Western geographical region
      of Ireland were invited to complete the secondary traumatic stress scale (STSS).
      A response rate of 90% (n = 105) was achieved. Most participants (n = 67/64%) met
      the criteria for secondary traumatic stress. A statistically significant finding
      was that the highest proportion (82%) of secondary traumatic stress existed in
      the staff nurse group (p = 0.042). Moreover, for those nurses reporting secondary
      traumatic stress, statistical significance was found for the variables 'change of
      career considered' (p = 0.017) and 'finds alcohol helpful in alleviating work
      related stress' (p = 0.004), when compared with nurses not reporting secondary
      traumatic stress. The findings suggest the need to examine current crisis
      management interventions and to introduce new systems to support nurses in Irish
      emergency departments. Moreover, because different types of traumatic events in
      the ED require different types of interventions, the prevention and management of
      STS among emergency department nurses must be tackled using a variety of
      approaches.

PMID- 24927979
TI  - The effect of static muscle forces on the fracture strength of the intact distal
      radius in vitro in response to simulated forward fall impacts.
AB  - The distal radius fracture (DRF) is a particularly dominant injury of the wrist,
      commonly resulting from a forward fall on an outstretched hand. In an attempt to
      reduce the prevalence, costs, and potential long-term pain/deformities associated
      with this injury, in vivo and in vitro investigations have sought to classify the
      kinematics and kinetics of DRFs. In vivo forward fall work has identified a
      preparatory muscle contraction that occurs in the upper extremity prior to peak
      impact force. The present investigation constitutes the first attempt to
      systematically determine the effect of static muscle forces on the fracture
      threshold of the distal radius in vitro. Paired human cadaveric forearm specimens
      were divided into two groups, one that had no muscle forces applied (i.e., right
      arms) and the other that had muscle forces applied to ECU, ECRL, FCU and FCR
      (i.e., left arms), with magnitudes based on peak muscle forces and in vivo lower
      bound forward fall activation patterns. The specimens were secured in a custom
      built pneumatic impact loading device and subjected to incremental impacts at pre
      fracture (25 J) and fracture (150 J) levels. Similar fracture forces (6565 (866)N
      and 8665 (5133)N), impulses (47 (6)Ns and 57 (30)Ns), and energies (152 (38)J and
      144 (45)J) were observed for both groups of specimens (p>0.05). Accordingly, it
      is suggested that, at the magnitudes presently simulated, muscle forces have
      little effect on the way the distal radius responds to forward fall initiated
      impact loading.

PMID- 24927980
TI  - Photophysical characterisation and studies of the effect of palladium(II)
      5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin on isometric contraction of
      isolated human mesenteric artery: good news for photodynamic therapy.
AB  - BACKGROUND: Considering the important roles of porphyrins in biological systems
      and their promising use in photodynamic therapy (PDT), the present work
      investigated the photophysical properties of palladium(II) 5,10,15,20-tetrakis-(4
      sulfonatophenyl)-porphyrin (PdTSPP) and the effects of non-activated by light
      form of this porphyrin on contractile behaviour of isolated healthy endothelium
      denuded human mesenteric arteries. METHODS: The photophysical characterisation of
      PdTSPP: the formation of the triplet states and the singlet oxygen were studied
      using laser flash photolysis. The effect of PdTSPP on the isometric contraction
      of artery segments from human mesentery was assessed utilising the precise method
      of artery isometric tension recording using Mulvany-Halpern wire myograph.
      RESULTS: We found that PdTSPP had a high lifetime of the triplet states
      tauT=270MUs. The calculated Stern Volmer rate constant kq=1.7*10(9)M(-1)s(-1)
      showed an efficient quenching by oxygen that indicated formation of singlet
      oxygen, O2((1)Deltag). The photophysical parameters of PdTSPP, in particular its
      ability to generate O2((1)Deltag) has defined it as an exceptionally interesting
      molecule for PDT. The results of the contraction study showed that PdTSPP applied
      in increasing concentrations (1-100MUM) had no effect on the basal tone of human
      mesenteric artery under isometric condition. Furthermore, PdTSPP failed to
      potentiate or to attenuate the isometric contraction of the artery preparations
      precontracted with high extracellular potassium (42mM KCl) or with 1nM endothelin
      1. CONCLUSIONS: The excellent photophysical properties of PdTSPP as well as the
      lack of an effect on the contractility of human vasculature in vitro characterise
      PdTSPP as a suitable compound for potential medical applications.

PMID- 24927981
TI  - Fertility preservation by photodynamic therapy combined with conization in young
      patients with early stage cervical cancer: a pilot study.
AB  - BACKGROUND: Vaginal radical trachelectomy (VRT) is the standard fertility
      preserving procedure for early stage cervical cancer patients. There have been
      reports in the literature, however, that VRT to be too radical procedure for
      early stage cervical cancer, as its post-operative obstetric morbidity was high.
      In this study, PDT with Loop electrosurgical excision procedure (LEEP) or
      conization was investigated as a less radical fertility preserving treatment
      alternative to VRT for early stage cervical cancer patients. METHODS: We analyzed
      data of 21 patients with early stage cervical cancer (stages IA-IIA) who
      underwent PDT with LEEP/conization from 2003 to 2012. LEEP or conization was
      performed before PDT in every case. For patients in stage IB1 or above, only
      those who were confirmed to be free of malignancy in frozen section by pelvic
      lymph node dissection received PDT. Surface photoillumination with red laser
      light at a wavelength of 630nm was applied to the cervix and the endocervical
      canal 48h after intravenous injection of 2mg/kg of photosensitizer. RESULTS:
      Median age of the 21 patients was 31 years old (range: 22-43), 19 patients
      (90.5%) of whom were nulliparous. Majority of the lesions were at stage IA1
      (47.6%) or IB1 (42.9%). Histologically, 80.9% were squamous cell carcinoma. 5
      patients (23.8%) had a lesion of 2cm or larger in diameter. There was one
      recurrence (4.7%) and no death during 52.6 months (6-114 months). Of the 13 women
      who attempted to get pregnant, 10 (76.9%) women conceived a total of 11
      pregnancies. The first and second trimester miscarriages were 2 and 1
      respectively, and 7 (70%) of the pregnancies reached the third trimester, of
      which 5 delivered at term. No tumor-related deaths or PDT-related severe adverse
      effects were noted. CONCLUSION: PDT combined with LEEP/conization could be an
      effective fertility sparing conservative treatment for young patients with early
      stage cervical cancer.

PMID- 24927982
TI  - Quantitative evaluation and visualization of size effect on cellular uptake of
      gold nanoparticles by multiphoton imaging-UV/Vis spectroscopic analysis.
AB  - With ever-increasing applications of nanoscale materials in the biomedical field,
      the impact of nanoparticle size on cellular uptake efficiency, dynamics, and
      mechanism has attracted numerous interests but still leaves many open questions.
      A combined "multiphoton imaging-UV/Vis spectroscopic analysis" method was applied
      for the first time for quantitative visualization and evaluation of the cellular
      uptake process of different-sized (15-, 30-, 50-, and 80-nm) gold nanoparticles
      (AuNPs). Quantitative analysis of the size effect on cellular uptake behavior of
      AuNPs from a stack of three-dimensional multiphoton laser scanning microscopy
      images is obtained. The technique allows for differentiating AuNPs present in
      external and internal subcellular components, giving detailed information for
      elucidating cellular uptake dynamics without particle labeling. The data show
      that the internalization extent of AuNPs is highly dependent on particles' sizes
      and incubation time. Due to sedimentation, 50- and 80-nm AuNPs are taken up to a
      greater extent than 15- and 30-nm particles after exposure for 24 h. However, the
      smaller particles' uptake velocity is significantly faster in the first 10 h,
      indicating a disparity in uptake kinetics for different-sized AuNPs. The finding
      from this study will improve our understanding of the cellular uptake mechanisms
      of different-sized nanoparticles and has great implications in developing AuNP
      based drug carriers with various sizes for different purposes.

PMID- 24927983
TI  - Difficult peripheral venous access: clinical evaluation of a catheter inserted
      with the Seldinger method under ultrasound guidance.
AB  - PURPOSE: A preliminary observational study was undertaken to evaluate the risk of
      failure of ultrasound-guided peripheral intravenous catheterization of a deep arm
      vein for a maximum of 7 days, after peripheral intravenous (PIV) cannulation
      failure. METHODS: This prospective study included patients referred to the
      intensive care unit for placement of a central line, a polyurethane cannula
      commercialized for arterial catheterization was used for peripheral venous
      cannulation. Catheter length and diameter were chosen based on preliminary
      ultrasound measurements of vein diameter and skin-vein distance. RESULTS:
      Catheterization was successful for all 29 patients. Mean vein diameter was 0.42
      +/- 0.39 cm; mean vein depth was 0.94 +/- 0.52 cm. Mean catheter duration was 6
      (median 7) days. Two occluded catheters were removed prematurely. No
      thrombophlebitis, catheter infection, or extravasation was observed. CONCLUSION:
      Our results suggest that catheters inserted with the Seldinger method are adapted
      to prolonged peripheral deep-vein infusion. Ultrasound can play a role in
      catheter monitoring by identifying early thrombosis formation.

PMID- 24927984
TI  - Early reversible acute kidney injury is associated with improved survival in
      septic shock.
AB  - INTRODUCTION: The fact that acute kidney injury (AKI) is associated with worse
      clinical outcomes forms the basis of most AKI prognostic scoring systems.
      However, early reversibility of renal dysfunction in acute illness is not
      considered in such systems. We sought to determine whether early (<=24 hours
      after shock documentation) reversibility of AKI was independently associated with
      in-hospital mortality in septic shock. METHODS: Patient information was derived
      from an international database of septic shock cases from 28 different
      institutions in Canada, the United States and Saudi Arabia. Data from a final
      cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009
      was analyzed. The following 4 definitions were used in regards to AKI status: (1)
      reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or
      incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI
      = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post
      shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock
      diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at
      6 hours post followed by improvement of AKI severity across at least one RIFLE
      category over the first 24 hours. Cox proportional hazards were used to determine
      the association between AKI status and in-hospital mortality. RESULTS: During the
      first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new
      AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was
      associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no
      AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR,
      1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across
      any RIFLE category associated with a significant decrease in mortality (HR, 0.53;
      95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute
      Physiology and Chronic Health Evaluation II score, lower age, and a smaller
      number of failed organs (excluding renal) on the day of shock as well as
      community-acquired infection were independently associated with reversible AKI.
      CONCLUSION: In septic shock, reversible AKI within the first 24 hours of
      admission confers a survival benefit compared to no, new, or persistent AKI.
      Prognostic AKI classification schemes should consider integration of early AKI
      reversibility into the scoring system.

PMID- 24927985
TI  - Frequency of acute changes found on head computed tomographies in critically ill
      patients: a retrospective cohort study.
AB  - PURPOSE: The frequency of positive findings on computed tomography (CT) of the
      head in critically ill patients who develop neurologic dysfunction is not known.
      MATERIALS AND METHODS: Cohort study of head CTs for patients admitted to 3
      intensive care units from 2005 to 2010. We documented the frequency of acute
      changes for all head CTs and for the subgroup of patients with altered mental
      status (AMS). We also examined associations between patient characteristics or
      medications administered before head CT and the odds of an acute change on head
      CT using multivariate logistic regression. RESULTS: During 11 338 intensive care
      unit admissions, there were 901 eligible head CTs on 706 patients (6% of
      patients). Among head CTs, 155 (17.2%) assessed concern of new focal deficit, 99
      (11.0%) concern for a seizure, and 635 (70.5%) for AMS. Acute changes were found
      on 109 (12.1%; 95% confidence interval [CI], 10.0%-14.2%) of all head CTs, and
      30% (22.4%-36.9%) of patients with focal deficits, 16.2% (8.8%-23.5%) of patients
      with seizures but only 7.4% (5.4%-9.4%) for patients with AMS. A diagnosis of
      sepsis was associated with a decreased odds of an acute change on head CT for all
      head CTs (odds ratio 0.61; 95% CI, 0.40-0.95; P = .028) but was not significantly
      associated with a decreased risk among the cohort of head CTs for AMS (odds ratio
      0.82; 95% CI, 0.41-1.62; P = .56). No other factors were associated with an
      altered risk of acute change on head CT for all patients in our cohort or for
      those with AMS. CONCLUSIONS: Acute changes on head CTs performed for concern
      regarding new focal neurologic deficit or seizures are frequent compared with
      those performed for AMS with a nonfocal examination. No specific patient
      characteristics or medications were associated with a large change in the
      likelihood of finding an acute change for patients with AMS.

PMID- 24927986
TI  - The handyman's brain: a neuroimaging meta-analysis describing the similarities
      and differences between grip type and pattern in humans.
AB  - BACKGROUND: Handgrip is a ubiquitous human movement that was critical in our
      evolution. However, the differences in brain activity between grip type (i.e.
      power or precision) and pattern (i.e. dynamic or static) are not fully
      understood. In order to address this, we performed Activation Likelihood
      Estimation (ALE) analysis between grip type and grip pattern using functional
      magnetic resonance imaging (fMRI) data. ALE provides a probabilistic summary of
      the BOLD response in hundreds of subjects, which is often beyond the scope of a
      single fMRI experiment. METHODS: We collected data from 28 functional magnetic
      resonance data sets, which included a total of 398 male and female subjects.
      Using ALE, we analyzed the BOLD response during power, precision, static and
      dynamic grip in a range of forces and age in right handed healthy individuals
      without physical impairment, cardiovascular or neurological dysfunction using a
      variety of grip tools, feedback and experimental training. RESULTS: Power grip
      generates unique activation in the postcentral gyrus (areas 1 and 3b) and
      precision grip generates unique activation in the supplementary motor area (SMA,
      area 6) and precentral gyrus (area 4a). Dynamic handgrip generates unique
      activation in the precentral gyrus (area 4p) and SMA (area 6) and of particular
      interest, both dynamic and static grip share activation in the area 2 of the
      postcentral gyrus, an area implicated in the evolution of handgrip. According to
      effect size analysis, precision and dynamic grip generates stronger activity than
      power and static, respectively. CONCLUSION: Our study demonstrates specific
      differences between grip type and pattern. However, there was a large degree of
      overlap in the pre and postcentral gyrus, SMA and areas of the frontal-parietal
      cerebellar network, which indicates that other mechanisms are potentially
      involved in regulating handgrip. Further, our study provides empirically based
      regions of interest, which can be downloaded here within, that can be used to
      more effectively study power grip in a range of populations and conditions.

PMID- 24927987
TI  - Syntax gradually segregates from semantics in the developing brain.
AB  - An essential computational component of the human language faculty is syntax as
      it regulates how words are combined into sentences. Although its neuroanatomical
      basis is well-specified in adults, its emergence in the maturing brain is not yet
      understood. Using event-related functional magnetic resonance imaging (fMRI) in a
      cross-sectional design, we discovered, that in contrast to what is known about
      adults 3-to-4- and 6-to-7-year-old children do not process syntax independently
      from semantics at the neural level already before these two types of information
      are integrated for the interpretation of a sentence. It is not until the end of
      the 10th year of life that children show a neural selectivity for syntax,
      segregated and gradually independent from semantics, in the left inferior frontal
      cortex as in the adult brain. Our results indicate that it takes until early
      adolescence for the domain-specific selectivity of syntax within the language
      network to develop. 

PMID- 24927988
TI  - Evaluation of viability-qPCR detection system on viable and dead Salmonella
      serovar Enteritidis.
AB  - The propidium monoazide (PMA) coupled with PCR (viability PCR) is used in
      foodborne pathogen detection in order to detect only viable bacteria. Originally
      presented to fully remove the signal of dead bacteria, the limits of the
      viability PCR rapidly came out in the literature. In this study, the use of PMA
      in a viability-qPCR (v-qPCR) was assessed on viable and dead cells of Salmonella
      enterica subsp. enterica serovar Enteritidis. The PMA treatment protocol was
      modified (dark incubation duration, concentration of PMA) to evaluate if a
      complete negative signal of dead Salmonella was possible. However, none of these
      modifications was found to improve the removal of the remaining qPCR signal
      observed in the presence of dead bacteria. The present research also underlines
      that PMA may unexpectedly decrease the qPCR signal observed on living S.
      Enteritidis at low concentration. Finally, the use of S. Enteritidis cells killed
      by processes altering or not the cell-wall/membrane gives us a clue to answering
      the question about the non-total extinction of the signal of dead cells sample in
      the v-qPCR assay. Indeed, the data strongly indicate that the remaining qPCR
      signal observed in non-culturable cells does not only depend on the cell
      wall/membrane integrity of the bacteria. According to these results, the authors
      suggest that for a rapid and reliable foodborne bacteria detection system, an
      enrichment followed by a qPCR analysis should be preferred to a v-qPCR. 

PMID- 24927989
TI  - Direct and fast detection of Alexandrium minutum algae by using high frequency
      microbalance.
AB  - In this paper, a simple detection of a toxic algae, Alexandrium minutum, was
      developed using highly sensitive quartz crystal microbalance. In terms of
      performance, compared with other conventional analytical tools, the main interest
      of our immunosensor is based on a fast and direct detection of these living
      cells. This system requires the use of one monoclonal antibody directed against
      the surface antigen of A. minutum. We demonstrate that the whole living and
      motile algae are caught and detected. The high specificity of the biosensor is
      also demonstrated by testing several other dinoflagellate species. The frequency
      shift is correlated to the A. minutum cell concentration. This simple system is
      potentially promising for environmental monitoring purposes. 

PMID- 24927990
TI  - Reconstructive surgery after burns: a 10-year follow-up study.
AB  - BACKGROUND: There is minimal insight into the prevalence of reconstructive
      surgery after burns. The objective of this study was to analyse the prevalence,
      predictors, indications, techniques and medical costs of reconstructive surgery
      after burns. METHODS: A retrospective cohort study was conducted in the three
      Dutch burn centres. Patients with acute burns, admitted from January 1998 until
      December 2001, were included. Data on patient and injury characteristics and
      reconstructive surgery details were collected in a 10-year follow-up period.
      RESULTS: In 13.0% (n=229/1768) of the patients with burns, reconstructive surgery
      was performed during the 10-year follow-up period. Mean number of reconstructive
      procedure per patient were 3.6 (range 1-25). Frequently reconstructed locations
      were hands and head/neck. The most important indication was scar contracture and
      the most applied technique was release plus random flaps/skin grafting. Mean
      medical costs of reconstructive surgery per patient over 10-years were ?8342.
      CONCLUSIONS: With this study we elucidated the reconstructive needs of patients
      after burns. The data presented can be used as reference in future studies that
      aim to improve scar quality of burns and decrease the need for reconstructive
      surgery.

PMID- 24927991
TI  - Inpatient peer support for adult burn survivors-a valuable resource: a
      phenomenological analysis of the Australian experience.
AB  - Peer support has long been recognised as an essential component of a supportive
      network for people facing adversity. In particular, burn survivor peer support is
      a valuable and credible resource available to those rehabilitating from a severe
      burn. The aim of this study was to explore burn survivors' experiences of
      providing and receiving inpatient peer support to develop an in-depth
      understanding of the influence during the rehabilitation journey. In 2011, twenty
      one burn survivors were recruited from four severe burn units across Australia. A
      qualitative phenomenological methodology was used to construct themes depicting
      survivors' experiences. Participants were selected through purposeful sampling,
      and data collected through in-depth individual semi-structured interviews. Data
      were analysed using Colaizzi's phenomenological method of data analysis. Central
      to burn rehabilitation was the notion of peer support having a significant impact
      on burn survivors' psychosocial rehabilitation. The emergent theme 'Burn Survivor
      Peer Support' identified five cluster themes: (1) Encouragement, inspiration and
      hope (2) Reassurance (3) The Importance of Timing (4) The Same Skin (5)
      Appropriate Matching. These findings demonstrate that peer support assists with
      fostering reassurance, hope and motivation in burn rehabilitation. A national
      network based on a clinician led inpatient burn survivor peer support programme
      could provide burn survivors across Australia, and in particular remote access
      locations, with the benefits of peer support necessary to endure the
      rehabilitation journey. 

PMID- 24927992
TI  - High effectiveness of triptolide, an active diterpenoid triepoxide, in
      suppressing Kir-channel currents from human glioma cells.
AB  - Triptolide (Trip), a diterpene triepoxide isolated from medicinal vine
      Trypterygium wilfordii Hook. F. possessed multiple biological activities
      including antineoplastic actions. However, no report concerning its effects on
      ion currents has been published. In this study, we attempted to determine whether
      this compound has any effects on ion currents in malignant glioma cells. The mRNA
      expression of KCNJ10 (Kir4.1) was detected in U373 glioma cells. The inwardly
      rectifying K(+) currents (IK(IR)) in U373 cells were almost fully blocked by
      BaCl2 (1mM). Trip (30 nM-10 MUM) effectively decreased the amplitude of IK(IR) in
      a concentration-dependent manner with an IC50 value of 0.72 MUM. In chlorotoxin
      treated U373 cells, Trip-mediated block of IK(IR) remained effective. Addition of
      Trip (3 MUM) slightly inhibited the amplitude of Ca(2+)-activated K(+) current
      and sustained K(+) outward current in U373 cells. In cell-attached configuration,
      when Trip was added to the bath, the activity of inwardly rectifying K(+) (Kir)
      channels diminished with no change in single-channel conductance. Its suppression
      of Kir channels was accompanied by a reduction in the slow component of mean open
      time. Under current-clamp conditions, addition of Trip depolarized the membrane
      along with changes in frequency histogram of resting potential. Block by this
      component of Kir4.1 channels may be an important mechanism underlying its actions
      on the functional activity of glioma cells. Targeting at Kir4.1 channels may be
      clinically useful as an adjunctive regimen to anti-cancer drugs.

PMID- 24927993
TI  - The influence of selected antihypertensive drugs on zinc, copper, and iron status
      in spontaneously hypertensive rats.
AB  - Mineral homeostasis in hypertensive patients may be affected by hypotensive
      drugs. The aim of this study was to assess the influence of selected
      antihypertensive drugs on mineral homeostasis in a rat model of hypertension.
      Eight-week-old male spontaneously hypertensive rats (SHRs) were treated with
      perindopril, metoprolol, indapamide, amlodipine, or no drug for 45 days. In
      another experiment, the SHRs were treated with indapamide or amlodipine in the
      presence of zinc and copper gluconate supplement. Lipids, glucose, and insulin
      levels along with superoxide dismutase and catalase activities were assayed in
      serum. Iron, zinc, and copper concentrations in serum, erythrocytes, and tissues
      were determined using the flame atomic absorption spectrometry. Blood pressure
      was measured using a tail-cuff plethysmograph. Treatment with indapamide and
      amlodipine was found to significantly lower zinc levels in serum, erythrocytes,
      livers, and spleens of the SHRs, as well as copper levels in the kidneys,
      compared with the control no-drug group. A markedly higher concentration of
      glucose was found in the indapamide-treated rats. Supplementing the indapamide
      treated SHRs with zinc and copper gluconate resulted in a significant decrease in
      both systolic and diastolic blood pressure, and also lowered serum glucose and
      triglyceride concentrations and HOMA (homeostasis model assessment-insulin
      resistance) values. The results show that indapamide and amlodipine disturb zinc
      and copper homeostasis in SHRs. Supplementation with zinc and copper restores
      mineral homeostasis in SHRs treated with indapamide and amlodipine, and also
      corrects metabolic imbalances while improving the antihypertensive efficiency of
      indapamide. 

PMID- 24927994
TI  - Inhibition of cardiac two-pore-domain K+ (K2P) channels--an emerging
      antiarrhythmic concept.
AB  - Effective and safe pharmacological management of cardiac arrhythmia still
      constitutes a major clinical challenge. Outward potassium currents mediated by
      two-pore-domain potassium (K2P) channels promote repolarization of excitable
      cells. In the heart, inhibition or genetic inactivation of K2P currents results
      in action potential prolongation. Human K2P3.1 (TASK-1) channels are
      predominantly expressed in the atria and represent targets for the treatment of
      atrial fibrillation. In addition, stretch-sensitive K2P2.1 (TREK-1) channels are
      implicated in mechanoelectrical feedback and arrhythmogenesis in atrial and
      ventricular tissue. K2P current inhibition by clinically used antiarrhythmic
      drugs indicates a role of the channels as potential drug targets. This work
      summarizes the current knowledge on function, pharmacology, and significance of
      cardiac K2P channels. Therapeutic implications with emphasis on atrial
      fibrillation are highlighted. 

PMID- 24927995
TI  - Prenatal lipopolysaccharide disrupts maternal behavior, reduces nest odor
      preference in pups, and induces anxiety: studies of F1 and F2 generations.
AB  - The present study analyzed the transgenerational effects of lipopolysaccharide
      (LPS; 100 MUg/kg) administration on gestational day 18 (GD18) of parental
      generation on maternal-pups interaction of F1 and F2 generations. Also the long
      term behavioral effects were observed in male of F2 generation. In F1 generation,
      the reproductive performance, maternal behavior, maternal aggressive behavior,
      and general activity in the open field in adulthood were analyzed. In F2
      generation, body weight at birth and at weaning, nest odor preference, and
      general activity in the open field and elevated plus maze in adulthood were
      assessed. Compared to controls, results showed that in the F1 generation,
      prenatal LPS exposure (1) increased the latency to full maternal behavior, but
      all of the females grouped the pups and presented full maternal behavior, (2)
      reduced the total time boxing and fighting, increased the frequency of retrieving
      the pups, and increased the number of bites, and (3) did not affect reproductive
      performance or general activity. In F2 generation, compared with controls, the
      LPS group exhibited (1) a decrease in body weight at weaning, (2) a decrease in
      nest odor preference, (3) a decrease in the percentage of time spent in the open
      arms, a decrease in the percentage of time spent in the center, and an increase
      in the time spent in the closed arms in the elevated plus maze, and (Huang et
      al.) no affect behavior in the open field. Prenatal LPS exposure improved
      maternal care in the F1 generation with regard to nursing and pup survival but
      did not improve the motivational parameters of maternal behavior likely because
      of a reduction of maternal stimulation by the pups. In the F2 generation, the
      reduction of nest odor preference in the pups suggests a less maternal
      recognition. In adulthood, these rats exhibited increased anxiety-like behavior.
      These data did not result from motor alterations because rats in both the F1 and
      F2 generations did not show alterations in open field behavior. This transfer of
      information across generations likely occurred through nongenetic means because
      the endotoxin was administered at the end of pregnancy. These results may have
      implications for clinical therapeutics in human disorders and evolution.

PMID- 24927997
TI  - Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2.
AB  - G protein-coupled receptor kinase 2 (GRK2) is an important serine/threonine
      kinase regulating different membrane receptors and intracellular proteins.
      Attenuation of Drosophila Gprk2 in embryos or adult flies induced a defective
      differentiation of somatic muscles, loss of fibers, and a flightless phenotype.
      In vertebrates, GRK2 hemizygous mice contained less but more hypertrophied
      skeletal muscle fibers than wild-type littermates. In C2C12 myoblasts,
      overexpression of a GRK2 kinase-deficient mutant (K220R) caused precocious
      differentiation of cells into immature myotubes, which were wider in size and
      contained more fused nuclei, while GRK2 overexpression blunted differentiation.
      Moreover, p38MAPK and Akt pathways were activated at an earlier stage and to a
      greater extent in K220R-expressing cells or upon kinase downregulation, while the
      activation of both kinases was impaired in GRK2-overexpressing cells. The
      impaired differentiation and fewer fusion events promoted by enhanced GRK2 levels
      were recapitulated by a p38MAPK mutant, which was able to mimic the inhibitory
      phosphorylation of p38MAPK by GRK2, whereas the blunted differentiation observed
      in GRK2-expressing clones was rescued in the presence of a constitutively active
      upstream stimulator of the p38MAPK pathway. These results suggest that balanced
      GRK2 function is necessary for a timely and complete myogenic process. 

PMID- 24927996
TI  - FW-04-806 inhibits proliferation and induces apoptosis in human breast cancer
      cells by binding to N-terminus of Hsp90 and disrupting Hsp90-Cdc37 complex
      formation.
AB  - BACKGROUND: Heat shock protein 90 (Hsp90) is a promising therapeutic target and
      inhibition of Hsp90 will presumably result in suppression of multiple signaling
      pathways. FW-04-806, a bis-oxazolyl macrolide compound extracted from China
      native Streptomyces FIM-04-806, was reported to be identical in structure to the
      polyketide Conglobatin. METHODS: We adopted the methods of chemproteomics,
      computational docking, immunoprecipitation, siRNA gene knock down, Quantitative
      Real-time PCR and xenograft models on the research of FW-04-806 antitumor
      mechanism, through the HER2-overexpressing breast cancer SKBR3 and HER2
      underexpressing breast cancer MCF-7 cell line. RESULTS: We have verified the
      direct binding of FW-04-806 to the N-terminal domain of Hsp90 and found that FW
      04-806 inhibits Hsp90/cell division cycle protein 37 (Cdc37) chaperone/co
      chaperone interactions, but does not affect ATP-binding capability of Hsp90,
      thereby leading to the degradation of multiple Hsp90 client proteins via the
      proteasome pathway. In breast cancer cell lines, FW-04-806 inhibits cell
      proliferation, caused G2/M cell cycle arrest, induced apoptosis, and
      downregulated Hsp90 client proteins HER2, Akt, Raf-1 and their phosphorylated
      forms (p-HER2, p-Akt) in a dose and time-dependent manner. Importantly, FW-04-806
      displays a better anti-tumor effect in HER2-overexpressed SKBR3 tumor xenograft
      model than in HER2-underexpressed MCF-7 model. The result is consistent with cell
      proliferation assay and in vitro apoptosis assay applied for SKBR-3 and MCF-7.
      Furthermore, FW-04-806 has a favorable toxicity profile. CONCLUSIONS: As a novel
      Hsp90 inhibitor, FW-04-806 binds to the N-terminal of Hsp90 and inhibits
      Hsp90/Cdc37 interaction, resulting in the disassociation of Hsp90/Cdc37/client
      complexes and the degradation of Hsp90 client proteins. FW-04-806 displays
      promising antitumor activity against breast cancer cells both in vitro and in
      vivo, especially for HER2-overexpressed breast cancer cells.

PMID- 24927998
TI  - [Potential role of CRELD1 gene in the pathogenesis of atrioventricular septal
      defect].
AB  - OBJECTIVE: To screen potential mutation of the CRELD1 gene in congenital
      atrioventricular septal defect (AVSD) and explore its functional implications.
      METHODS: Fragments encompassing the 11 coding exons of CRELD1 gene, including at
      least 50 bp of flanking intronic regions, were amplified with PCR and subjected
      to DNA sequencing. Results of sequencing were compared with predicted sequence
      from the GenBank database. Eukaryotic expression vector pcDNA3.1CRELD1 containing
      the mutational sequence was constructed. Western blotting and real-time
      fluorescent quantitative reverse transcription polymerase chain reaction (FQ RT
      PCR) was applied to examine the expression of CRELD1, Tenascin C and Aggrecan.
      RESULTS: C857G was identified in a girl with an isolated partial AVSD. The
      mutation has resulted in a substitution of Alanine for Proline at amino acid 286
      in the first cbEGF domain. Western blotting and FQ RT-PCR confirmed that the
      P286R missense mutation has been a gain-of-function mutation. Compared with the
      unloaded control, the Aggrecan mRNA expression was downregulated for both wild
      type and mutant type samples (t=140.27 vs. 26.36, P < 0.01). The downregulation
      was more significant in mutant type (t=25.69, P=0.002). There was no significant
      difference of the Tenascin C expression between wild-type and the unload control
      (t=1.167, P> 0.05), whilst the Tenascin C expression was up-regulated in mutant
      type (t=6.66, P=0.022). CONCLUSION: Mutation of the CRELD1 gene may increase the
      risk for AVSD rather than being directly causative. The P286R mutation of CRELD1
      can downregulate the expression of Aggrecan and upregulates the expression of
      Tenascin C protein, both of which are crucial to extracellular matrix in the
      formation of the atrioventricular septum. The P286R mutation of CRELD1 may be
      correlated to the occurrence of AVSD.

PMID- 24927999
TI  - [Genetic analysis of ASS1, ASL and SLC25A13 in citrullinemia patients].
AB  - OBJECTIVE: To detect potential mutations of Y9ASS1, ASL and SLC25A13 genes in
      four patients manifesting citrullinemia. METHODS: Genomic DNA was extracted from
      peripheral blood leukocytes. Exons and their flanking sequences of the three
      genes were amplified with polymerase chain reaction and subjected to direct DNA
      sequencing. RESULTS: Based on DNA sequence analysis, one case was diagnosed with
      argininosuccinate synthetase deficiency, and the mutation type (ASS1 gene) was
      c.236C>T (p.S79F) + c.431C>G (p.P144R). Two cases were diagnosed with
      argininosuccinic aciduria (ASL gene), and their gene mutations were c.434A>G
      (p.D145G) + c.1366C>T (p.R456W) and c.331C>T (p.R111W) + IVS8+2insT,
      respectively. A thirteen months boy who carried a heterozygous 851del4 mutation
      (SLC25A13 gene) was diagnosed with citrullinemia adult-onset type II. CONCLUSION:
      Through analysis of relevant pathogenic genes, four patients have been diagnosed.

PMID- 24928000
TI  - [Analysis of FGFR2 gene mutations in two Chinese families with Crouzon syndrome].
AB  - OBJECTIVE: To detect potential mutations of fibroblast growth factor receptor 2
      gene (FGFR2) in two Chinese families with Crouzon syndrome. METHODS: Genomic DNA
      was extracted from peripheral blood leukocytes of 20 members from two affected
      families. All of the 18 exons of the FGFR2 gene were amplified with polymerase
      chain reaction and sequenced after purification. RESULTS: A missense mutation
      c.868T>C (p.W290R) in exon 8 of the FGFR2 gene was found solely in 2 affected
      members from family 1. Another missense mutation c.833G>T (p.C278F) in exon 8 was
      found solely in 5 affected members of family 2. CONCLUSION: The missense
      mutations of the FGFR2 gene are responsible for the Crouzon syndrome in the two
      families. The c.868T>C missense mutation is reported for the first time in
      Chinese population.

PMID- 24928001
TI  - [Identification of a pathogenic microduplication in a Chinese split-hand/split
      foot malformation family].
AB  - OBJECTIVE To identify the potential pathogenic mutation in a Chinese family with
      split hand/foot malformation (SHFM). METHODS Affymetrix SNP 6.0 array was used to
      perform a genome-wide copy number variations scan, and quantitative real-time PCR
      (qPCR) was applied to validate the identified genomic duplication. RESULTS A ~560
      kb microduplication on the chromosome 10q24 was identified. The qPCR assay
      confirmed the presence of this microduplication in all the available affected
      family members. CONCLUSION The ~560 kb microduplication is probably the
      pathogenic mutation underlying the SHFM phenotype in the studied family. 

PMID- 24928002
TI  - [Genetic analysis and prenatal diagnosis of two Chinese families with split hand
      foot malformation].
AB  - OBJECTIVE: To identify genomic aberrations underlying pathogenesis of split hand
      foot malformation (SHFM) in two Chinese families, and to provide genetic
      counseling and prenatal diagnosis for them. METHODS: Two sets of peripheral blood
      and amniotic fluid samples were collected from the patients. One was processed
      with routine culture and karyotype analysis. For another set, DNA was extracted
      and analyzed with array-based comparative genomic hybridization (array-CGH).
      RESULTS: Karyotype analysis of peripheral blood samples for both probands was
      normal. Karyotype analysis of the amniotic fluid from family 1 has found no
      abnormality. However, analysis of amniotic fluid samples from the second family
      showed del(7)(q21q22.1). By array-CGH analysis, both blood and amniotic fluid
      samples from the first family showed a 662.3 kb dup(10q24.31q24.32). Array-CGH
      analysis of the blood sample from the second family was normal, whilst analysis
      of amniotic fluid sample revealed a 19.97 Mb del(7q11.23q21.3). CONCLUSION: Array
      CGH features high resolution, high accuracy and rapid diagnosis for unbalanced
      chromosomal aberration. The dup(10q24.31q24.32) and 19.97 Mb del(7q11.23q21.3)
      have been the cause of SHFM in the two families. Genetic counseling and prenatal
      diagnosis have been provided for both families in order to prevent this birth
      defect.

PMID- 24928003
TI  - [Genetic analysis for a family with Cockayne syndrome].
AB  - OBJECTIVE: To identify potential mutations among three sisters from a Chinese
      family suspected with Cockayne syndrome for growth and psychomotor retardation,
      and to offer genetic counseling and prenatal diagnosis for the family. METHODS: G
      banded karyotyping, microarray comparative genomic hybridization (CM-CGH), whole
      genome exon high-throughput sequencing and Sanger sequencing were employed to
      identify potential genetic variations for the three patients and their parents.
      RESULTS: Whole exome sequencing has identified two novel missense mutations,
      i.e., c.1595A>G (p.Asp532Gly) and c.1607T>G (p.Leu536Trp), in exon 7 of excision
      repair cross-complementing rodent repair deficiency, complementation group 6
      (ERCC6) gene. Sanger sequencing confirmed that all of the three sisters have
      inherited one of the mutations (c.1607T>G) from their father and another
      (c.1595A>G) from their mother. CONCLUSION: Three sisters have all been identified
      as double heterozygote for mutations c.1607T>G and c.1595A>G and were diagnosed
      with Cockayne syndrome.

PMID- 24928004
TI  - [Analysis of CYP21A2 gene mutations in two families with 21-hydroxylase
      deficiency].
AB  - OBJECTIVE: To analyze CYP21A2 gene mutation in two families with 21-hydroxylase
      deficiency (21-OHD) and to explore the correlation between genotype and clinical
      phenotype. METHODS: Two patients with 21-OHD and their families were
      investigated. CYP21A2 gene mutation was analyzed by PCR and direct sequencing.
      RESULTS: The probands from family 1 and 2 have been respectively diagnosed with
      simple virilizing and non-classical 21-OHD. Both showed increased baseline serum
      17hydroxyprogesterone, testosterone and adrenocorticotropic hormone (ACTH), but
      had no evidence of salt loss. Computer tomography revealed bilateral adrenal
      hyperplasia in both patients. After 1 year treatment, both had conceived
      successfully. DNA sequencing revealed that the proband of family 1 had compound
      heterozygous mutations for IVS2 13 A>G and Ile172Asn. Her father was heterozygous
      for Ile172Asn, whilst her mother and brother were heterozygous for IVS213A/C>G.
      In family 2, the proband was heterozygous for Arg341Trp and Gln318X. Her father,
      sister and nephew were heterozygous for Arg341Trp, whilst her mother was
      heterozygous for Gln318X. her brother and niece were non-affected. Carriers of
      single heterozygous mutations in both families had no clinical sign. CONCLUSION:
      In both families, the disease has been caused by compound heterozygous mutations,
      for which there has been a good genotype-phenotype agreement. Screening of
      CYP21A2 gene can facilitate both diagnosis and genetic counseling.

PMID- 24928005
TI  - [Mutation analysis of STK11 gene in a Chinese family with Peutz-Jeghers
      syndrome].
AB  - OBJECTIVE: To investigate STK11 gene mutation in a pedigree with Peutz-Jeghers
      syndrome (PJS). METHODS: A pedigree of PJS was investigated. DNA was extracted
      from peripheral blood samples from affected and unaffected members of the
      pedigree and 100 unrelated healthy controls. PCR was performed to amplify all of
      the 9 coding exons of STK11 gene. PCR products were directly sequenced to detect
      mutation. RESULTS: A missense mutation p.F354L (c.1062C>G) in exon 8 of the STK11
      gene has been identified in all patients with PJS, but was not found in normal
      individuals from the pedigree and 100 unrelated controls. CONCLUSION: A missense
      mutation p.F354L of STK11 gene probably underlies the disease in this pedigree.

PMID- 24928006
TI  - [Study of mutations of presenilin 1 gene in early-onset familial Alzheimers
      disease].
AB  - OBJECTIVE: Mutations of presenilin 1 (PSEN1) gene are the most frequent cause for
      familial Alzheimers disease (AD). This study was set to explore potential
      mutation of PSEN1 gene in a Chinese family featuring early-onset Alzheimers
      disease (FAD). METHODS: DNA was isolated from peripheral blood samples from 17
      members of the FAD family as well as 10 patients with sporadic Alzheimers disease
      and 100 healthy subjects. With polymerase chain reaction (PCR) and Sanger
      sequencing, exons 113 of the PSEN1 gene were analyzed. RESULTS: DNA sequencing
      has revealed a heterozygous point mutation from G to A at position 1133
      (Gly378Glu) of exon 11 of PSEN1 gene in 6 members from the family, among whom 5
      were patients with dementia, whilst the remaining 1 was clinically normal but
      under onset age. The same mutation was not found in all other patients and the
      normal controls. CONCLUSION: A novel missense mutation of the PSEN1 gene,
      Gly378Glu, probably underlies the autosomal dominant early-onset FAD in this
      Chinese family.

PMID- 24928007
TI  - [Array comparative genomic hybridization analysis of early-stage arrested human
      embryos].
AB  - OBJECTIVE: To investigate chromosomal euploidies in early-stage arrested human
      embryos. METHODS: To determine the euploidy status of the 24 chromosomes, 13
      embryos were analyzed, which included 5 arrested at 4-cell stage, 4 arrested at 8
      cell stage, and 4 embryos at blastocyst stage regardless of their morphological
      scores. All embryos were subjected to biopsy, whole genome amplification, and
      array comparative genome hybridization analysis. RESULTS: Chromosome euploidies
      of the arrested embryos can be normal, aberrant and chaotic. Mosaicism is
      prevalent in early stage cleavage, whilst most of the blastocysts, even with poor
      morphology, are normal diploid. CONCLUSION: Arrested embryo may have normal
      chromosomes euploidy. Mosaicism is common in cleavage stage embryos. Early stage
      embryo arrest may not be solely attributable to chromosomal aneuploidies and
      needs further research.

PMID- 24928008
TI  - [Relationship between Line 1 methylation and clinical data of non-small cell lung
      cancer].
AB  - OBJECTIVE: To explore the impact of Line-1 methylation on clinical features of
      non-small cell lung cancer and its connection with smoking and other living
      habits. METHODS: Pyrosequencing was used to determine the extent of Line-1
      methylation in cancer and adjacent tissues derived from 197 patients with primary
      non-small cell lung cancer. Non-conditional logistic regression analysis was
      performed to correlate the level of Line-1 methylation with clinical features and
      living habits of the patients. RESULTS: Line-1 methylation for cancer tissue and
      adjacent tissue has measured 68.20+/-11.63 and 78.90+/-2.09, respectively (P <
      0.01), and has been associated with TNM staging, smoking history and
      histopathological types. CONCLUSION: Lung cancer tissue Line-1 methylation level
      is closely related with clinical features and smoking. There is also a
      correlation between histopathological types of lung cancer and relative
      hypomethylation of Line-1.

PMID- 24928009
TI  - [Effect of PARP1 inhibitor PJ34 on multi-drug resistance in human multiple
      myeloma cell line and its relationship with FA/BRCA pathway].
AB  - OBJECTIVE: To investigate the effect of PARP1 inhibitor PJ34 on multi-drug
      resistance in a human multiple myeloma cell line and its connection with FA/BRCA
      pathway in DNA damage repair. METHODS: A CCK8 assay was used to measure the
      inhibition rate. Real-time quantitative PCR was used to detect expression changes
      of DNA repair genes involved in the FA/BRCA pathway. Western blotting assay was
      used to detect expression of key protein FANCD2 in the FA/BRCA pathway. Annexin
      VFITC/PI double staining flow cytometry was used to measure cell apoptosis
      induced by PJ34. A COMET assay was used to detect the effect of PJ34 on DNA
      damage repair. RESULTS: PJ34 could significantly enhance the sensitivity of
      RPMI8226/R cells to melphalan. The IC50 value of melphalan was dropped from 20.43
      mol/L to 7.8 mol/L. PJ34 could inhibit the DNA damage repair, and the effect was
      related with the inhibition of FA/BRCA pathway. PJ34 and melphalan showed a
      synergistic effect in promoting the apoptosis of RPMI8226/R cells. CONCLUSION:
      PJ34 can reverse the resistance of RPMI8226/R cells to melphalan by inhibiting
      the FA/BRCA pathway, which in turn can induce suppression of DNA damage repair.
      Therefore, PJ34 may have clinical value in overcoming the multi-drug resistance
      of multiple myeloma.

PMID- 24928010
TI  - [Expression of peroxisome proliferators-activated receptor in glioma and its
      effect on the growth of human glioma cells].
AB  - OBJECTIVE: To study the expression of peroxisome proliferators-activated receptor
      (PPAR) in human glioma tissue and its influence on tumor growth. METHODS:
      Expression of PPAR mRNA in glioma tissue was determined by real-time reverse
      transcription polymerase chain reaction (RT-PCR). Subsequently, MTT (3-(4, 5)
      dimethylthiahiazo(-z-y1)-3, 5-di-phenytetrazoliumromide) assay, flow cytometry,
      reactive oxygen species assay kit and Western blotting were used to assay U87
      cells with agonist activity of PPAR. RESULTS: The data demonstrated that the
      expression of PPAR in glioma was low and negatively correlated with its
      pathological grade. Activation of PPAR suppresses tumor cell proliferation,
      delays the cell cycle at G1 phrase, and induces apoptosis and accumulation of
      reactive oxygen species (ROS) in U87 cells. CONCLUSION: The expression of PPAR
      mRNA in human glioma was low. PPAR protein plays a critical role in the
      progression of glioma via the PPAR signal pathway.

PMID- 24928011
TI  - [Identification of a NFB responsive element within the dimethylarginine
      dimethylaminohydrolase 2 gene promoter].
AB  - OBJECTIVES: To identify a NFB responsive element within the dimethylarginine
      dimethylaminohydrolase 2 gene (DDAH) promoter and demonstrate its role in DDAH2
      transactivation. METHODS: DDAH2 promoter was analyzed with software to identify
      potential binding sites of transcription factors. A series of truncated DDAH2
      promoter luciferase reporter plasmids were constructed and transfected into human
      embryonic kidney derived HEK293 cells. Luciferase assays were carried out to
      analyze the activity of the promoter. Electrophoresis mobility shift assay (EMSA)
      and chromatin immunoprecipitation (ChIP) were used to identify the NFB responsive
      element in vitro and in vivo. DDAH2 promoter luciferase reporter plasmid with
      mutated NFB site was constructed and transfected into cells, and its activity was
      compared with that of the wild-type plasmid. RESULTS: Potential bindings sites of
      many transcription factors were found within the DDAH2 promoter. The
      transcription activity of the DDAH2 promoter was high, and -530 to -437 was a
      positive regulating region. -476 to -469 of the DDAH2 promoter was a NFB
      responsive element, to which NFB can specifically bind. Mutation of the NFB
      element could significantly decrease the DDAH2 promoter activity. CONCLUSION: 
      476 to -469 of the DDAH2 promoter was a NFB responsive element and is important
      for the transactivation of DDAH2.

PMID- 24928012
TI  - [Advances in research based on twins reared apart].
AB  - The design of twins reared apart, very rare genetic epidemiological resources has
      been hailed as fascinating experiment of nature. However, not so many studies
      have been based on it due to the difficulty in recruiting the participants. It
      also makes the only existing research on twins raised apart particularly
      valuable. How to utilize these resources fully will be the focus of this research
      area. This review will overview its design background, basic hypothesis, and
      current status of research and give advice for the research in this field in
      China. 

PMID- 24928013
TI  - [Recent advances of study on hereditary diffuse leukoencephalopathy with
      spheroids].
AB  - Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a
      rare autosomal dominant leukoencephalopathy disease, and colony stimulating
      factor 1 receptor (CSF1R) is the only gene in which mutations are known to cause
      HDLS. HDLS should be suspected in individuals with progressive neurological
      decline, characteristic MR imaging findings, and positive family history. This
      article reviews recent advance in imaging findings, clinical manifestations,
      genetic counseling and management in HDLS. 

PMID- 24928014
TI  - [Advance in studies on dopamine system related genetic polymorphisms associated
      with nicotine dependence].
AB  - Nicotine is the main component for smoking addiction. It is widely believed that
      nicotine dependence is heritable. Many studies are committed to study the effects
      of specific gene polymorphisms connect with nicotine dependence. Release of
      dopamine has been considered the most important channel for nicotine dependence.
      This paper provides a review for recent advance in studies on dopamine system
      related genetic polymorphisms associated with nicotine dependence. 

PMID- 24928015
TI  - [Genetic diagnosis of Duchenne/Becker muscular dystrophy by MLPA].
AB  - OBJECTIVE: To assess the value of multiplex ligation-dependent probe
      amplification (MLPA) for the genetic and prenatal diagnosis of Duchenne/Becker
      muscular dystrophy (DMD/BMD). METHODS: Forty seven patients clinically diagnosed
      or suspected with DMD/BMD were recruited. Deletion or duplication of the 79 exons
      of the DMD gene were detected by MLPA. PCR and sequencing were used to detect
      single exon deletion. MLPA was also used for identifying carriers. For cases
      requesting prenatal diagnosis, short tandem repeat (STR) capillary
      electrophoresis, linkage analysis and MLPA were applied to determine fetal DMD
      gene. RESULTS: Among the 47 patients, deletions and duplications encompassing one
      or more exons were identified in 31 and 7 cases with MLPA, respectively. Seven
      patients had single exon deletions. However, one of which was actually a point
      mutation in the probe-conjugated region and was confirmed by PCR and sequencing.
      Of the 23 mothers with MLPA positive sons, 13 were found to carry either
      deletions or duplications. Prenatal diagnosis has identified 2 male affected
      fetuses and 3 female carrier fetuses in the 13 cases examined, which was in
      conformity with linkage analysis. CONCLUSION: Our data demonstrated that MLPA is
      a rapid, direct and reliable method for detecting deletions or duplications of
      the DMD gene. It can also indicate small changes within the sequences detected by
      the probe. Combing MLPA with PCR, sequencing and linkage analysis could make the
      genetic diagnosis of DMD/BMD more accurate.

PMID- 24928016
TI  - [Screening and analysis of a new mutation of COL1A1 gene in a family with
      osteogenesis imperfecta].
AB  - OBJECTIVE: To investigate mutation of COL1A1 gene and analyze the relationship
      between genotype and clinical phenotype in a family with osteogenesis imperfecta
      (OI). METHODS: The family history of an OI pedigree, along with clinical data,
      was collected. Blood samples from the proband and his families, as well as 50
      normal controls, were collected. Mutation of COL1A1 gene was screened using PCR
      high resolution melting (PCR-HRM) and validated by sequencing. RESULTS: PCR HRM
      method showed an abnormal result in proband COL1A133_34 exons, which Tm was
      87.7C, in contrast to the normal control (wt) Tm of 87.9+/-0.06C. There was a
      significant difference between the proband and the normal control with the
      standardization curve and the difference curves. DNA sequencing showed that
      Y9COL1A1 gene exons 33_34 has lost a C base (c.2321delC), which resulted in a
      frameshift mutation and caused an premature termination codon (UAA) at amino acid
      334, i.e., p.Pro774LeufsX334 The father and grandfather of the proband, both
      suffered from OI, were verified to be heterozygous for the same mutation. The
      same mutation was not found in 50 normal controls. Database search confirmed this
      to be a novel mutation. Pedigree analysis suggested that it has an autosomal
      dominant inheritance. The proband and patients from the family were clinically
      diagnosed as OI type I. CONCLUSION: The study has identified a novel mutation of
      COL1A1 gene, c.2321delC. This frameshift mutation has caused a premature stop
      codon and reduced collagen type synthesis, characterized by a lighter OI clinical
      phenotype.

PMID- 24928017
TI  - [A family with interphalangeal synarthrophysis].

PMID- 24928018
TI  - [Multiple endocrine neoplasia type 2A caused by a p.C618R RET proto-oncogene
      mutation in a Chinese pedigree].
AB  - OBJECTIVE: To explore the clinical characteristics and significance of RET proto
      oncogene screening in multiple endocrine neoplasia type 2A (MEN2A). METHODS:
      Comprehensive medical history was obtained for 5 members from a 3-generation
      family from southern China. Clinical investigations have included biochemical
      testing, imaging, and screening of germline RET proto-oncogene mutations.
      RESULTS: Genetic screening has revealed a missense mutation at codon 618(TGC>CGC)
      of exon 10 in 3 patients(p.C618R), which was consistent with their clinical
      manifestations. For the 3 individuals, the age at diagnosis was 21, 26 and 36 yr,
      and the maximum diameter of medullary thyroid carcinoma was 22, 25 and 39 cm,
      respectively. The 36-year-old female patient initially underwent right total
      thyroidectomy plus right neck lymph node dissection. Four years later, she again
      underwent left adrenal tumorectomy and left total thyroidectomy plus left neck
      lymph node dissection. The 21-year-old male patient underwent right total
      thyroidectomy plus right modified neck dissection. The follow-up was respectively
      146 and 26 months following the initial operation. Two patients still presented
      elevated calcitonin and had bilateral neck lymph node masses and/or left thyroid
      masses on imaging examination. The 26-year-old female patient, who presented
      bilateral thyroid masses and elevated calcitonin, has refused thyroidectomy.
      CONCLUSION: Combined family survey and RET gene screening can facilitate early
      diagnosis and surgical treatment to improve the prognosis.

PMID- 24928019
TI  - [Screening of variation in the promoter of PPARGC1A gene and study of its
      association with the risk of type 2 diabetes in ethnic Hans from Beijing].
AB  - OBJECTIVE: To study the baseline distribution of polymorphisms in the promoter of
      peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in
      ethnic Hans from Beijing, and to assess their association with type 2 diabetes
      (T2DM). METHODS: A 2-stage study was designed. Firstly, the promoter region of
      PPAGC1A gene was screened with PCRRFLP in a small population (n=216,
      T2DM/control: 104/112), which was followed by a replication study of a larger
      group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood
      lipid, height, weight, waist circumference, and blood pressure were measured in
      all subjects. Potential association was assessed by logistic regression. Linkage
      disequilibrium and haplotype analysis were conducted with Haploview software.
      RESULTS: Five polymorphisms were identified with Sanger sequencing, among which T
      2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included
      for genotypic analysis based on their moderate levels of heterozygosity. No
      significant difference was found between the two groups. When adjusted for age
      and gender confounding, we have combined the OR values from population 1 and
      population 2 based on Mantel-Haenszel fixed model, and recognized a mild
      contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM
      (P=0.03, OR=118). No haplotype was associated with T2DM after permutation
      correction. CONCLUSION: The C allele of -1999C/G ( rs2946386) in the promoter
      region of the PPARGC1A gene is mildly associated with T2DM. Variations in the
      promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our
      population.

PMID- 24928020
TI  - [Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han
      population].
AB  - OBJECTIVE: To assess the association of neural development-related genes LIS1and
      TSNAX with bipolar disorder in a Chinese Han population. METHODS: Three hundred
      and eight five patients (including 188 males and 197 females) from Guangzhou
      Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual
      of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from
      the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of
      the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an
      Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes
      were performed with Plink 1.07 software. RESULTS: Analysis of the total sample
      has failed to find any association of SNP or haplotype of the two genes with BDI
      (P> 0.05). When patients were divided into subgroups with or without psychotic
      symptom, no significant association of the two genes was found with psychotic BDI
      or non-psychotic BDI (P> 0.05). No significant association was found between any
      SNP and haplotype of two genes and female BDI or male BDI, nor were significant
      association found between age of onset and LIS1 and TSNAX gene polymorphisms.
      CONCLUSION: Our results indicated that LIS1 and TSNAX genes are not associated
      with susceptibility to bipolar I disorder in Chinese Han population.

PMID- 24928021
TI  - [Association of programmed cell death 1 gene polymorphisms with dilated
      cardiomyopathy in Chinese Han population].
AB  - OBJECTIVE: To investigate the association between programmed death 1 (PDCD1) gene
      polymorphism and dilated cardiomyopathy (DCM). METHODS: Two single nucleotide
      polymorphisms (SNPs) of the PDCD1 gene, rs2227981, rs2227982, were genotyped and
      detected in 340 DCM patients and 401 healthy controls using the method of
      polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP). The
      genotype frequencies and allele frequencies of SNPs were compared between DCM
      patients and normal controls. RESULTS: The genotype and allele distributions of
      rs2227982 were significantly different between the patients with DCM and the
      controls. The frequencies of TT genotype and T allele of rs2227982 were higher in
      the patients than those in the controls (35.3% vs. 23.4%, P < 0.01, OR=2.37,
      95%CI: 1.57-3.57; 58.5% vs. 47.4%, P < 0.01, OR=1.58, 95%CI: 1.28-1.93,
      respectively). No association was observed for rs2227981 between the DCM patients
      and the controls. CONCLUSION: rs2227982 in PDCD1 gene is association with DCM in
      Chinese Han population, which supported PDCD1 as a susceptibility gene for DCM.
      TT genotypes and T allele in rs2227982 may be associated with significantly
      increased risk of DCM.

PMID- 24928022
TI  - [Impact of six genetic polymorphisms on Warfarin maintenance dose variation in
      Chinese Han population].
AB  - OBJECTIVE: To evaluate the effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2
      gene polymorphisms on Warfarin maintenance dose variation in Chinese Han
      Population. METHODS: Four hundred eighty-eight patients with prosthetic heart
      valves, atrial fibrillation or pulmonary thromboembolism and achieved stable
      Warfarin dose were enrolled. TaqMan probe or direct sequencing were used to
      genotype Y9VKORC1, CYP2C9, GGCX, EPHX1 and CYP4F2 gene polymorphisms. Demographic
      characteristics, stable therapeutic dose of Warfarin and concomitant medications
      were collected for all patients. The effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1
      and CYP4F2 gene polymorphisms, demographic characteristics and concomitant
      medications on Warfarin daily maintenance dose were analyzed with statistical
      method. RESULTS: VKORC1 and CYP2C9 gene polymorphisms could explain more than 50%
      Warfarin maintenance dose variation in recruited patients, while CYP4F2 gene
      polymorphisms could only explain 1%. GGCX, PROC and EPHX1 gene polymorphisms had
      no impact no Warfarin maintenance dose. VKORC1 and CYP2C9 gene polymorphisms have
      a greater impact on Warfarin maintenance dose compared with demographic
      characteristics and concomitant medications. CONCLUSION: VKORC1 and CYP2C9 gene
      polymorphisms have a significant impact on Warfarin maintenance dose in Chinese
      Han population.

PMID- 24928023
TI  - [Characterization of muscular involvement in patients with Duchenne muscular
      dystrophy by magnetic resonance imaging].
AB  - OBJECTIVE: To study the order and degree of muscular affection in patients with
      Duchenne muscular dystrophy (DMD) during the course of disease. METHODS:
      Multiplex ligation dependent probe amplification (MLPA) was used to detect
      potential mutation of dystrophin gene. Magnetic resonance imaging (MRI) was used
      to scan the anteromedial aspect of thigh muscles. RESULTS: All of the 6 patients
      were found to have deletion or duplication mutations. The order of affection has
      been gluteus maximus, adductor magnus, quadriceps femoris, rectus femoris and
      biceps muscle of the thigh, while semimembranous muscle, semitendinosus,
      sartorius muscle and musculus gracilis are selectively affected and in a
      decreasing order. CONCLUSION: MRI can reflect the order, extent and degree of
      skeletal muscle involvement in patients with DMD, and can reflect pathological
      changes of damaged skeletal muscle at each stage, which may provide an important
      means for patient examination and diagnosis. No apparent correlation between the
      severity of disease and the nature of mutations was noted.

PMID- 24928024
TI  - [Value of second-time invasive prenatal diagnosis in the current circumstances].
AB  - OBJECTIVE: To assess the safety of repeated invasive prenatal diagnosis primarily
      due to failed culture of amniotic cells. METHODS: Between January 2000 and
      October 2012, 167 cases required repeated invasive prenatal diagnosis among a
      total of 5304 amniocentesis cases. Clinical outcome and karyotypes were analyzed
      to calculate the rate of fetal loss. RESULTS: For the 167 re-sampled cases, the
      indications have included failed amniocyte culture (121 cases), chromosome
      mosaicisms (23 cases), failed amniocentesis (21 cases), and request for
      confirmation (2 cases). No fetal loss has occurred. All samples were cultured
      successfully. Fourteen cases (8.38%) have been found with an abnormal karyotype.
      Four mosaic trisomic cases (2 mosaic trisomy 16, 1 mosaic trisomy 20, and 1
      mosaic trisomy 8) were verified to be normal. CONCLUSION: Repeated invasive
      prenatal diagnosis does not increase the rate of fetal loss. It can be
      recommended to cases with failed amniocyte culture. Caution should be undertaken
      when counseling prenatally detected mosaicism trisomies.

PMID- 24928025
TI  - [Predictive value of HLA-DRB1 gene for the treatment of unexplained recurrent
      spontaneous abortion with paternal lymphocyte alloimmunization therapy in Henan
      Hans].
AB  - OBJECTIVE: To explore the value of HLA-DRB1 gene in predicting the outcome of
      unexplained recurrent spontaneous abortion (URSA) treated with paternal
      lymphocyte alloimmunization therapy (PLAT) in Henan Hans. METHODS: Three hundred
      URSA patients were recruited. Following PLAT treatment, they were divided into
      two groups according to the outcome of pregnancy. Polymerase chain reaction
      sequence specific primer (PCR-SSP) were conducted to analyze the HLA-DRB1 gene.
      RESULTS: For those who have received PLAT treatment, the frequency of HLA-DRB1*11
      was significantly lower in successfully treated cases than those with abortion
      (0.052 vs. 0.110, P < 0.05, OR=0448), whilst the frequency of HLA-DRB1*15 was
      significantly greater in the former (0.207 vs. 0.100, P < 0.05, OR=2.352).
      CONCLUSION: For patients who have received PLAT treatment, those with HLA-DRB1*15
      are more likely to conceive that those with HLA-DRB1*11.

PMID- 24928026
TI  - [Development of a method for the separation of HLA-A, -B and -C haploid using
      biotinylated probe and streptavidin magnetic beads].
AB  - OBJECTIVE: To develop a method for separating the human leukocyte antigen (HLA)
      A, -B and -C haploid using biotinylated probes and streptavidin magnetic beads in
      order to solve ambiguous HLA genotyping results. METHODS: Based on sequence
      information of HLA alleles from the IMGT/HLA database, the 5-biotinylated probes
      were designed. The probe was mixed and extended with corresponding genomic DNA,
      and incubated with streptavidin magnetic beads, which could form a streptavidin
      magnetic beads-biotin-probe DNA complex. The unique DNA haploid binding to
      corresponding probe was isolated after washes and elution. The separated haploid
      genomic DNA was used as template for HLA-A, -B and -C loci amplification and
      sequencing analysis. RESULTS: Among the 12 HLA-A probes, 19 HLA-B probes and 13
      HLA-C probes, DNA sequencing has confirmed that 9 HLA-A probes, 9 HLA-B probes
      and 5 HLA-C probes could successfully separate the haploid from genomic DNA
      samples. CONCLUSION: The developed method for HLA-A, -B and -C haploid separation
      is reliable, which can solve certain ambiguity and improve the accuracy of HLA
      genotyping.

PMID- 24928027
TI  - [Study of genetic polymorphisms of 12 short tandem repeats on X chromosome in
      ethnic Han population from Hebei Province].
AB  - OBJECTIVE: To investigate genetic polymorphisms of 12 X chromosome short tandem
      repeat (X-STR) loci in ethnic Hebei Han population using an Investigator Argus X
      12 amplification kit. METHODS: DNA was extracted for 198 unrelated individuals
      (96 males and 102 females) and amplified with a fluorescence labeled multiplex
      PCR system. PCR products were separated and genotyped with capillary array
      electrophoresis. RESULTS: Only DXS10103 and DXS10101 showed significant linkage
      disequilibrium at the 12 X-STR loci. One hundred and forty-eight alleles,
      including 22 off-ladder (OL) alleles, were observed at the 12 X-STR loci in the
      population. The heterozygosity and polymorphic information content (PIC) were
      0.5074-0.9143 and 0.4377-0.9079, respectively. The power of discrimination (PD)
      was 0.5074-0.9143 in males and 0.6876-0.9863 in females. The mean exclusion
      chance was 0.4377-0.9079 in the trios cases and 0.2984-0.8373 in the duo cases,
      respectively. CONCLUSION: The Investigator Argus X12 amplification system is
      highly polymorphic in ethnic Han population from Hebei and is useful for personal
      identification and paternity testing.

PMID- 24928028
TI  - [Facioscapulohumeral muscular dystrophy - twelve cases from two pedigrees].

PMID- 24928029
TI  - [Osteopoikilosis - a family with five cases].

PMID- 24928030
TI  - Drug development and discovery: challenges and opportunities.

PMID- 24928031
TI  - Prognostic and predictive relevance of circulating tumor cells in patients with
      non-small-cell lung cancer.

PMID- 24928032
TI  - Mortality in Parkinson's disease is not associated with the severity of early
      dopaminergic defect.
AB  - BACKGROUND: Although there is a relationship between the extent of striatal
      dopaminergic defect and the severity of motor symptoms in Parkinson's disease
      (PD), studies investigating associations between dopamine and mortality in PD
      have been scarce. If a relationship were established, dopamine restoring
      neuroprotective treatments could be used to decrease mortality. The objective of
      this study was to determine whether the initial degree of hypodopaminergic
      defect, as measured by 6-[(18)F]fluoro-L-DOPA positron emission tomography (FDOPA
      PET), can predict patient survival. METHODS: The study population included a
      cohort of 88 recently diagnosed and untreated patients with PD who were
      clinically examined and scanned with FDOPA-PET between the years 1998 and 2000.
      The date of exit for the survival analysis was in April 2013 with a follow-up
      interval of 13-15 years. The survival model included FDOPA uptake, age, sex and
      symptom severity as explaining factors. Death certificates of the patients were
      obtained, and causes of death were analyzed. RESULTS: Mortality rate was 56.8%.
      Although higher age (p < 0.001) and greater motor symptom severity (p < 0.05)
      were associated with increased mortality, there was no association between
      survival and FDOPA uptake in any striatal subregion (p > 0.48). CONCLUSION:
      Unlike age and early motor symptom severity, dopamine synthesis capacity, as
      measured with PET, does not predict survival in PD.

PMID- 24928033
TI  - Varicella zoster virus DNA does not accumulate in infected human neurons.
AB  - Varicella zoster virus (VZV) is an exclusively human neurotropic
      alphaherpesvirus. It is unclear why human neurons infected in vitro with VZV at
      low multiplicity of infection do not exhibit a cytopathic effect (CPE) even
      though all VZV genes are transcribed, VZV proteins from all kinetic classes are
      translated and minimal infectious virus is produced. Here, we show that the lack
      of VZV-induced CPE correlates with the low abundance of viral DNA. 

PMID- 24928034
TI  - Downregulation of IRF4 induces lytic reactivation of KSHV in primary effusion
      lymphoma cells.
AB  - Primary effusion lymphoma (PEL), associated with the latent infection by KSHV,
      constitutively expresses interferon-regulatory factor 4 (IRF4). We recently
      showed that IRF4 differentially regulates expression of cellular interferon
      stimulated genes (ISGs) and viral genes (Forero et al., 2013). Here, using
      inducible IRF4 knockdown, we demonstrate that IRF4 silencing results in enhanced
      transcription of KSHV replication transactivator RTA. As a result viral
      transcription is increased leading to virus reactivation. Taken together, our
      results show that IRF4 helps maintain the balance between latency and KSHV
      reactivation in PEL cells. 

PMID- 24928035
TI  - Increased Serpin A5 levels in the cervicovaginal fluid of HIV-1 exposed
      seronegatives suggest that a subtle balance between serine proteases and their
      inhibitors may determine susceptibility to HIV-1 infection.
AB  - HIV-exposed seronegative individuals (HESNs) are persons who remain seronegative
      despite repeated exposure to HIV, suggesting an in vivo resistance mechanism to
      HIV. Elucidation of endogenous factors responsible for this phenomenon may aid in
      the development of new classes of microbicides and therapeutics. We compared
      cervicovaginal protein abundance profiles between high-risk HESN and two control
      groups: low-risk HESN and HIV-positives. Four iTRAQ-based quantitative
      experiments were performed using samples classified based on presence/absence of
      particular gynaecological conditions. After statistical analysis, two proteins
      were shown to be differentially abundant between high-risk HESNs and control
      groups. Serpin A5, a serine proteinase inhibitor and Myeloblastin, a serine
      protease, were up- and downregulated, respectively. Commercially available ELISA
      assays were used to confirm differential Serpin A5 levels. These results suggest
      that HIV resistance in CVF of HESNs is the result of a delicate balance between
      two complementary mechanisms: downregulation of serine proteinases and
      upregulation of their inhibitors. 

PMID- 24928036
TI  - Cell entry of lymphocytic choriomeningitis virus is restricted in myotubes.
AB  - In mice persistently infected since birth with the prototypic arenavirus
      lymphocytic choriomeningitis viurs, viral antigen and RNA are readily detected in
      most organs and cell types but remarkably absent in skeletal muscle. Here we
      report that mouse C2C12 myoblasts that are readily infected by LCMV, become
      highly refractory to LCMV infection upon their differentiation into myotubes.
      Myotube's resistance to LCMV was not due to an intracellular restriction of virus
      replication but rather an impaired cell entry mediated by the LCMV surface
      glycoprotein. Our findings provide an explanation for the observation that in
      LCMV carrier mice myotubes, which are constantly exposed to blood-containing
      virus, remain free of viral antigen and RNA despite myotubes express high levels
      of the LCMV receptor alpha dystroglycan and do not pose an intracellular blockade
      to LCMV multiplication.

PMID- 24928037
TI  - The R35 residue of the influenza A virus NS1 protein has minimal effects on
      nuclear localization but alters virus replication through disrupting protein
      dimerization.
AB  - The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in
      the amino terminal region. This NLS overlaps sequences that are important for RNA
      binding as well as protein dimerization. To assess the significance of the NS1
      NLS on influenza virus replication, the NLS amino acids were individually mutated
      to alanines and recombinant viruses encoding these mutations were rescued.
      Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed
      minimal changes in replication or NS1 protein nuclear localization. Recombinant
      viruses encoding NS1 R35A were not recovered but viruses containing second site
      mutations at position D39 in addition to the R35A mutation were isolated. The
      mutations at position 39 were shown to partially restore NS1 protein dimerization
      but had minimal effects on nuclear localization. These data indicate that the
      amino acids in the NS1 NLS region play a more important role in protein
      dimerization compared to nuclear localization. 

PMID- 24928038
TI  - Position of the kissing-loop interaction associated with PTE-type 3'CITEs can
      affect enhancement of cap-independent translation.
AB  - The Panicum mosaic virus-like translation enhancer (PTE) functions as a cap
      independent translation enhancer (3'CITE) in members of several Tombusviridae
      genera including 7/19 carmoviruses. For nearly all PTE, a kissing-loop connects
      the element with a hairpin found in several conserved locations in the genomic
      RNA (5' terminal hairpin or ~100 nt from the 5' end) and small subgenomic RNA
      (~63 nt from the 5' end). Moving the interaction closer to the 5' end in reporter
      mRNAs using Saguaro cactus virus (SCV) sequences had either a minimal or
      substantial negative effect on translation. Movement of the kissing loop from
      position 104 to the SCV 5' terminal hairpin also reduced translation by 4-fold.
      These results suggest that relocating the PTE kissing loop closer to the 5' end
      reduces PTE efficiency, in contrast to results for the Barley yellow dwarf BTE
      and Tomato bushy stunt virus Y-shaped 3'CITEs, suggesting that different 3'CITEs
      have different bridging requirements.

PMID- 24928040
TI  - The application of multiple miRNA response elements enables oncolytic
      adenoviruses to possess specificity to glioma cells.
AB  - Adenovirus-mediated virotherapy is one of the promising therapeutic approaches
      for glioma treatment. However, its replication efficiency and specificity still
      failed to meet the requirements for clinical treatment. To improve the anti-tumor
      activity and specificity of oncolytic adenoviruses (OA), we applied multiple
      miRNA response elements (MREs) of miR-124, miR-128, miR-146b and miR-218, whose
      expressions were downregulated in glioma cells, to enable OA to be specific to
      glioma. Adenoviral E1A protein regulated by these 4 MREs (OA-4MREs) was shown to
      be highly expressed in glioma cells, but not in normal cells. The selective E1A
      expression led to glioma-specific replication and cytotoxicity of OA-4MREs.
      Animal experiments also showed that OA-4MREs exhibited improved anti-tumor
      activities for both subcutaneous and intracranial glioma xenografts, without
      significant toxicity to normal brain and liver tissues. Collectively, we
      demonstrated that oncolytic adenovirus, whose replication was regulated by MREs,
      may be promising biological agents for glioma treatment. 

PMID- 24928039
TI  - Identification and characterization of a macrophage-tropic SIV envelope
      glycoprotein variant in blood from early infection in SIVmac251-infected
      macaques.
AB  - Macrophages play an important role in HIV/SIV pathogenesis by serving as a
      reservoir for viral persistence in brain and other tissues. Infected macrophages
      have been detected in brain early after infection, but macrophage-tropic viruses
      are rarely isolated until late-stage infection. Little is known about early
      variants that establish persistent infection in brain. Here, we characterize a
      unique macrophage-tropic SIV envelope glycoprotein (Env) variant from two weeks
      post-infection in blood of an SIVmac251-infected macaque that is closely related
      to sequences in brain from animals with neurological disease. SIVmac251 clones
      expressing this Env are highly fusogenic, and replicate efficiently in T cells
      and macrophages. N173 and N481 were identified as novel determinants of
      macrophage tropism and neutralization sensitivity. These results imply that
      macrophage-tropic SIV capable of establishing viral reservoirs in brain can be
      present in blood during early infection. Furthermore, these SIVmac251 clones will
      be useful for studies on pathogenesis, eradication, and vaccines. 

PMID- 24928041
TI  - DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer.
AB  - The C-type lectin receptors (CLRs) expressed on dendritic cells (DCs), in
      particular DC-SIGN and DCIR, likely play an important role in HIV-1 early
      infection. Here, we systematically compared the capture and transfer capability
      of DC-SIGN and DCIR using a wide range of HIV-1 isolates. Our results indicated
      that DC-SIGN plays a stronger role than DCIR in DC-mediated HIV-1 capture and
      transfer. This was further strengthened by the data from transient and stable
      transfectants, showing that DC-SIGN had better capability, compared with DCIR in
      HIV-1 capture and transfer. Following constructing and analyzing a series of
      soluble DC-SIGN and DCIR truncates and chimeras, we demonstrated that the neck
      domain, but not the CRD, renders DC-SIGN higher binding affinity to gp120 likely
      via the formation of tetramerization. Our findings provide insights into CLR
      mediated HIV-1 capture and transfer, highlighting potential targets for
      intervention strategies against gp120-CLR interactions. 

PMID- 24928042
TI  - The nuclear retention signal of HPV16 L2 protein is essential for incoming viral
      genome to transverse the trans-Golgi network.
AB  - The Human papillomavirus (HPV) capsid is composed of the major and minor capsid
      proteins, L1 and L2, respectively. Infectious entry requires a complex series of
      conformational changes in both proteins that lead to uptake and allow uncoating
      to occur. During entry, the capsid is disassembled and host cyclophilins
      dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16
      L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi
      network (TGN) but fails to egress. Our data provide further evidence that HPV16
      traffics through the TGN and demonstrates that L2 is essential for TGN egress.
      Furthermore, we show that cyclophilin activity is required for the L2/DNA complex
      to be transported to the TGN which is accompanied by a reduced L1 protein levels.

PMID- 24928043
TI  - Mapping of the exchangeable and dispensable domains of the RNA 2-encoded 2A(HP)
      protein of arabis mosaic nepovirus.
AB  - The N-terminal domains of the RNA 2-encoded 2A(HP) proteins of the arabis mosaic
      (ArMV) and grapevine fanleaf (GFLV) nepoviruses were shown to be highly variable
      and a hotspot for intra- and inter-species recombination events. Chimeric ArMV-NW
      clones in which the N-terminal domain of 2A(HP) or the entire 2A(HP) of GFLV
      isolates replaced the corresponding domains of ArMV retained their infectivity,
      showing that the 2A(HP) proteins of ArMV-NW and GFLV are exchangeable. ArMN-NW
      clones with deletions of the N-terminal, core, or C-terminal domains of the ArMV
      NW 2A(HP) were infectious in Chenopodium quinoa although viral RNA (especially
      RNA 2) accumulated at reduced levels. In contrast, deletion of the entire 2A(HP)
      protein or of the C-terminal two thirds of the protein abolished infectivity of
      the ArMV-NW clones. These results suggest that multiple functional domains are
      distributed throughout the 2A(HP) protein and are essential for the accumulation
      of viral RNA 2. 

PMID- 24928044
TI  - Diversity of the murine antibody response targeting influenza A(H1N1pdm09)
      hemagglutinin.
AB  - We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted
      with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B
      cells. Based on the redundancy in germline gene utilization, we inferred that
      between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the
      anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were
      employed most frequently. A representative panel of antibodies were cloned and
      expressed to confirm reactivity with H1N1pdm09 HA. The majority of the
      recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09
      hemagglutination. Three of these antibodies were subtype-specific cross-reactive,
      binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with
      A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of
      the influenza anti-HA antibody repertoire profile induced following infection and
      vaccination, which may facilitate the development of influenza vaccines that are
      more protective and broadly neutralizing. IMPORTANCE: Protection against
      influenza viruses is mediated mainly by antibodies, and in most cases this
      antibody response is narrow, only providing protection against closely related
      viruses. In spite of this limited range of protection, recent findings indicate
      that individuals immune to one influenza virus may contain antibodies (generally
      a minority of the overall response) that are more broadly reactive. These
      findings have raised the possibility that influenza vaccines could induce a more
      broadly protective response, reducing the need for frequent vaccine strain
      changes. However, interpretation of these observations is hampered by the lack of
      quantitative characterization of the antibody repertoire. In this study, we used
      single-cell cloning of influenza HA-specific B cells to assess the diversity and
      nature of the antibody response to influenza hemagglutinin in mice. Our findings
      help to put bounds on the diversity of the anti-hemagglutinin antibody response,
      as well as characterizing the cross-reactivity, affinity, and molecular nature of
      the antibody response.

PMID- 24928045
TI  - Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4.
AB  - Coronaviruses replicate their genomes in association with rearranged cellular
      membranes. The coronavirus nonstructural integral membrane proteins (nsps) 3, 4
      and 6, are key players in the formation of the rearranged membranes. Previously,
      we demonstrated that nsp3 and nsp4 interact and that their co-expression results
      in the relocalization of these proteins from the endoplasmic reticulum (ER) into
      discrete perinuclear foci. We now show that these foci correspond to areas of
      rearranged ER-derived membranes, which display increased membrane curvature.
      These structures, which were able to recruit other nsps, were only detected when
      nsp3 and nsp4 were derived from the same coronavirus species. We propose, based
      on the analysis of a large number of nsp3 and nsp4 mutants, that interaction
      between the large luminal loops of these proteins drives the formation of
      membrane rearrangements, onto which the coronavirus replication-transcription
      complexes assemble in infected cells. 

PMID- 24928046
TI  - Biogenesis of non-structural protein 1 (nsp1) and nsp1-mediated type I interferon
      modulation in arteriviruses.
AB  - Type I interferons (IFNs-alpha/beta) play a key role for the antiviral state of
      host, and the porcine arterivirus; porcine reproductive and respiratory syndrome
      virus (PRRSV), has been shown to down-regulate the production of IFNs during
      infection. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral
      IFN antagonist, and the nsp1alpha subunit of nsp1 has been shown to degrade the
      CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus
      resulting in the suppression of IFN production. The study was expanded to other
      member viruses in the family Arteriviridae: equine arteritis virus (EAV), murine
      lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus
      (SHFV). While PRRSV-nsp1 and LDV-nsp1 were auto-cleaved to produce the nsp1alpha
      and nsp1beta subunits, EAV-nsp1 remained uncleaved. SHFV-nsp1 was initially
      predicted to be cleaved to generate three subunits (nsp1alpha, nsp1beta, and
      nsp1gamma), but only two subunits were generated as SHFV-nsp1alphabeta and SHFV
      nsp1gamma. The papain-like cysteine protease (PLP) 1alpha motif in nsp1alpha
      remained inactive for SHFV, and only the PLP1beta motif of nsp1beta was
      functional to generate SHFV-nsp1gamma subunit. All subunits of arterivirus nsp1
      were localized in the both nucleus and cytoplasm, but PRRSV-nsp1beta, LDV
      nsp1beta, EAV-nsp1, and SHFV-nsp1gamma were predominantly found in the nucleus.
      All subunits of arterivirus nsp1 contained the IFN suppressive activity and
      inhibited both interferon regulatory factor 3 (IRF3) and NF-kappaB mediated IFN
      promoter activities. Similar to PRRSV-nsp1alpha, CBP degradation was evident in
      cells expressing LDV-nsp1alpha and SHFV-nsp1gamma, but no such degradation was
      observed for EAV-nsp1. Regardless of CBP degradation, all subunits of arterivirus
      nsp1 suppressed the IFN-sensitive response element (ISRE)-promoter activities.
      Our data show that the nsp1-mediated IFN modulation is a common strategy for all
      arteriviruses but their mechanism of action may differ from each other. 

PMID- 24928047
TI  - Processing bodies accumulate in human cytomegalovirus-infected cells and do not
      affect viral replication at high multiplicity of infection.
AB  - Translationally silenced mRNAs are recruited to two major classes of RNA granules
      in the cytoplasm, processing bodies (PBs) and stress granules (SGs). We show that
      PBs accumulated after human cytomegalovirus (HCMV) infection. PB assembly after
      HCMV infection was also detected in the presence of the protein synthesis
      inhibitor, cycloheximide, but required active RNA synthesis. UV-inactivated HCMV
      virions were sufficient to induce PB accumulation in HFF cells treated with
      cycloheximide. Viral IE1 RNA did not colocalize with PBs, and we could not detect
      an effect of PB accumulation on viral growth. These results may indicate that
      HCMV inhibits the colocalization of IE1 mRNA with PBs, preventing IE1 mRNA decay
      and translational inhibition. 

PMID- 24928048
TI  - Porcine reproductive and respiratory syndrome virus infection activates NOD2-RIP2
      signal pathway in MARC-145 cells.
AB  - Nucleotide-binding oligomerization domains (NOD)-like receptors (NLRs) evolve as
      a group of germline-encoded receptors that detect cytosolic pathogen-associated
      molecular patterns. Porcine reproductive and respiratory syndrome virus (PRRSV)
      is an Arterivirus that has been devastating the swine industry worldwide. By
      examining the expression kinetics of ten selected NLRs, NOD2 and NLRP3 were found
      to be continuously up-regulated in PRRSV-infected MARC-145 cells during 48 h of
      post-infection. Further study revealed that PRRSV infection enhanced the
      expression and phosphorylation of RIP2. Knockdown of NOD2 and RIP2 by siRNA
      significantly decreased PRRSV-induced phosphorylation of NF-kappaB subunit p65,
      JNK, Erk and p38 MAPK, as well as the expression of IL-6, IL-8, TNF-alpha, and
      RANTES in MARC-145 cells. Moreover, increased expression of NOD2 and RIP2 mRNA
      were observed in alveolar macrophages isolated from PRRSV-challenged piglets at
      3, 7 and 10 day post-challenge. Collectively, our results revealed that PRRSV
      infection activates NOD2-RIP2 signaling pathway to induce pro-inflammatory
      response.

PMID- 24928049
TI  - Modulation of innate immune signaling by the secreted form of the West Nile virus
      NS1 glycoprotein.
AB  - West Nile virus (WNV) employs several different strategies to escape the innate
      immune response. We have previously demonstrated that the WNV NS1 protein
      interferes with signal transduction from Toll-like receptor 3 (TLR3). NS1 is a
      glycoprotein that can be found intracellularly or associated with the plasma
      membrane. In addition, NS1 is secreted to high levels during flavivirus
      infections. We investigated whether the secreted form of NS1 inhibits innate
      immune signaling pathways in uninfected cells. Secreted NS1 (sNS1) was purified
      from supernatants of cells engineered to express the protein. Purified sNS1
      associated with and repressed TLR3-induced cytokine production by HeLa cells, and
      inhibited signaling from TLR3 and other TLRs in bone marrow-derived macrophages
      and dendritic cells. Footpad administration of sNS1 showed the protein associated
      predominantly with macrophages and dendritic cells in the draining lymph node.
      Additionally, sNS1 significantly reduced TLR3 signaling and WNV replicon particle
      mediated cytokine transcription in popliteal lymph nodes. 

PMID- 24928050
TI  - Mutational profiling of the variability of individual amino acid positions in the
      hepatitis B virus matrix domain.
AB  - The hepatitis B virus (HBV) is formed by budding. A stretch of 22 amino acids
      (aa) (matrix domain, MD, R103 - S124) in the large envelope protein L is crucial
      for virion formation and probably establishes contact to the nucleocapsid. Here,
      we assess the impact of sequence variations at numerous individual aa positions
      within the MD on virion formation. We generated panels of L mutants covering all
      19 possible aa for 11 positions and tested the capacity of these mutants to
      rescue virus production by an L-defective HBV genome. At four positions (L112,
      R113, P117, W122), any replacement of the wild type (WT) aa reduced virus
      assembly to undetectable levels. Virus production was strongly diminished by
      substitutions at five other positions (R103, T106, S115, H116, A119). Only two
      tested positions (D114, Q118) tolerated several substitutions. The restricted
      positions may represent promising targets for the development of novel antiviral
      strategies. 

PMID- 24928051
TI  - Production and characterization of high-titer serum-free cell culture grown
      hepatitis C virus particles of genotype 1-6.
AB  - Recently, cell culture systems producing hepatitis C virus particles (HCVcc) were
      developed. Establishment of serum-free culture conditions is expected to
      facilitate development of a whole-virus inactivated HCV vaccine. We describe
      generation of genotype 1-6 serum-free HCVcc (sf-HCVcc) from Huh7.5 hepatoma cells
      cultured in adenovirus expression medium. Compared to HCVcc, sf-HCVcc showed 0.6
      2.1 log10 higher infectivity titers (4.7-6.2 log10 Focus Forming Units/mL),
      possibly due to increased release and specific infectivity of sf-HCVcc. In
      contrast to HCVcc, sf-HCVcc had a homogeneous single-peak density profile. Entry
      of sf-HCVcc depended on HCV co-receptors CD81, LDLr, and SR-BI, and clathrin
      mediated endocytosis. HCVcc and sf-HCVcc were neutralized similarly by chronic
      phase patient sera and by human monoclonal antibodies targeting conformational
      epitopes. Thus, we developed serum-free culture systems producing high-titer
      single-density sf-HCVcc, showing similar biological properties as HCVcc. This
      methodology has the potential to advance HCV vaccine development and to
      facilitate biophysical studies of HCV.

PMID- 24928052
TI  - A two-center retrospective review of the hematologic evaluation and laboratory
      abnormalities in suspected victims of non-accidental injury.
AB  - Investigation for bleeding disorders in the context of suspected non-accidental
      injury (NAI) is inconsistent. We reviewed the hematologic evaluation of children
      who presented with symptoms of bleeding and/or bruising suspicious for NAI to
      determine the frequency of hematologic tests, abnormal hematologic laboratory
      results, and hematologic diagnoses. A retrospective cohort study design was
      employed at two freestanding academic children's hospitals. ICD-9 codes for NAI
      were used to identify 427 evaluable patients. Medical records were queried for
      the details of clinical and laboratory evaluations at the initial presentation
      concerning for NAI. The median age for the population was 326 days (range 1 day
      14 years), 58% were male. Primary bleeding symptoms included intracranial
      hemorrhage (31.8%) and bruising (68.2%). Hematologic laboratory tests performed
      included complete blood cell count in 62.3%, prothrombin time (PT) in 55.0%, and
      activated partial thromboplastin time (aPTT) in 53.6%; fibrinogen in 27.6%;
      factor activity in 17.1%; von Willebrand disease evaluation in 14.5%; and
      platelet function analyzer in 11.7%. Prolonged laboratory values were seen in
      22.5% of PT and 17.4% of aPTT assays; 66.0% of abnormal PTs and 87.5% of abnormal
      aPTTs were repeated. In our cohort, 0.7% (3 of 427) of the population was
      diagnosed with a condition predisposing to bleeding. In children with bleeding
      symptoms concerning for NAI, hemostatic evaluation is inconsistent. Abnormal
      tests are not routinely repeated, and investigation for the most common bleeding
      disorder, von Willebrand disease, is rare. Further research into the extent and
      appropriate timing of the evaluation is warranted. 

PMID- 24928053
TI  - The effects of apple pomace, bentonite and calcium superphosphate on swine manure
      aerobic composting.
AB  - The effects of additives such as apple pomace, bentonite and calcium
      superphosphate on swine manure composting were investigated in a self-built
      aerated static box (90 L) by assessing their influences on the transformation of
      nitrogen, carbon, phosphorous and compost maturity. The results showed that
      additives all prolonged the thermophilic stage in composting compared to control.
      Nitrogen losses amounted to 34-58% of the initial nitrogen, in which ammonia
      volatilization accounted for 0.3-4.6%. Calcium superphosphate was helpful in
      facilitating composting process as it significantly reduced the ammonia
      volatilization during thermophilic stage and increased the contents of total
      nitrogen and phosphorous in compost, but bentonite increased the ammonia
      volatilization and reduced the total nitrogen concentration. It suggested that
      calcium superphosphate is an effective additive for keeping nitrogen during swine
      manure composting.

PMID- 24928054
TI  - Efficacy of ovarian tissue cryopreservation in a major European center.
AB  - PURPOSE: To evaluate the effect of cryopreservation and thawing of ovarian tissue
      from oncological patients opting for fertility preservation on ovarian tissue
      viability. METHODS: In this prospective cohort study, the ovarian tissue
      viability before and after cryopreservation and thawing was measured for 25 newly
      diagnosed oncological patients who had their ovarian tissue cryopreserved.
      Outcome measures were follicle integrity (histology), follicle viability (Calcein
      viability assay), steroid hormone production (estradiol and progesterone
      production in vitro) and overall tissue viability (glucose uptake in vitro). This
      study was conducted at a Cryobank for storage of ovarian tissue in a university
      hospital. RESULTS: Cryopreserved/thawed ovarian tissue showed a decreased glucose
      uptake when compared to tissue that had not been cryopreserved. In addition, a
      diminished E2 and P4 production was observed after cryopreservation and thawing,
      despite the fact that numbers of viable follicles as determined by the Calcein
      viability assay were comparable. Histological examination revealed a higher
      percentage of degenerated follicles after cryopreservation and thawing.
      CONCLUSIONS: Ovarian tissue cryopreservation and thawing impairs the viability of
      ovarian tissue in oncological patients opting for fertility preservation.

PMID- 24928055
TI  - Expression of the estrogen receptors and steroidogenic enzymes involved in
      estradiol formation in the monkey vagina.
AB  - OBJECTIVE: Estrogens are well recognized to have beneficial effects on
      vulvovaginal atrophy because of menopause. The distribution of estrogen receptors
      and enzymes responsible for estradiol (E2) formation within the vagina may
      provide insight into how dehydroepiandrosterone, a precursor of both estrogens
      and androgens, improves vulvovaginal atrophy. STUDY DESIGN: The purpose of the
      study was to determine where the steroidogenic enzymes responsible for E2
      formation as well as estrogen receptors are localized in vaginal specimens
      collected from cynomolgus monkeys (Macaca fascicularis), the closest model to the
      human. HSD3B1, HSD17B1, HSD17B5, HSD17B12, aromatase (CYP19A1), estrogen receptor
      (ER)-alpha, and ER-beta were measured or localized by quantitative real-time
      polymerase chain reaction, immunohistochemistry, and immunofluorescence.
      Estrogens were quantified by liquid chromatography/tandem mass spectrometry.
      RESULTS: All steroidogenic enzymes and estrogen receptors are localized mainly in
      the superficial layer of the stratified squamous epithelium, blood vessel walls,
      and muscle fibers of the vagina. Immunolabeling of HSD17B5 and HSD17B12 shows
      that these enzymes are uniformly distributed from the basal membrane to the
      superficial keratinized cells, whereas HSD3B1 and aromatase are particularly
      localized in the outer (external) portion of the epithelial layer. ER-alpha and
      ER-beta are also distributed within the vaginal epithelium, with expression
      especially elevated at the basal membrane level. CONCLUSION: The enzymes
      responsible for E2 formation as well as ERs are expressed mainly in the
      superficial layer of the stratified epithelium as well as the muscle layer of the
      vagina. The present data provide morphologic and biochemical support for the role
      of local dehydroepiandrosterone transformation into estrogens in regulating
      epithelial cell maturation, pH, fluid secretion, smooth muscle activity, and
      blood flow regulation in the primate vagina.

PMID- 24928057
TI  - Modelling beyond data is uninformative: a comment on "State-space modelling
      reveals proximate causes of harbour seal population declines" by Matthiopoulos et
      al.
AB  - Detailed models have the potential to reveal important processes underlying
      patterns in data. However, model fitting depends on the availability of
      sufficient data, and the results obtained from the models depend on detailed
      assumptions. In a recent paper, Matthiopoulos et al. fitted Bayesian state space
      models to a limited dataset and attempted to explain the recent trajectory of the
      harbour seal population in the Moray Firth, in northern Scotland. They went on to
      suggest that the results could help explain recent declines in other nearby
      populations. This Comment describes the implications of understating the
      uncertainty that the model required for convergence, questions the robustness of
      the results, highlights the differences between the areas, and cautions against
      extrapolating across these populations. The distinction between models that can
      be fitted to a dataset and those that provide useful information about the
      systems that generated the data is also considered. 

PMID- 24928058
TI  - Electrically conducting silver/guar gum/poly(acrylic acid) nanocomposite.
AB  - This article describes the synthesis of an electrically conducting silver/guar
      gum/poly(acrylic acid) nanocomposite hydrogel. The synthesis process started with
      grafting acrylic acid monomers onto the natural polymer guar gum by the use of
      ammonium persulphate as a free radical initiator in acid medium. Guar
      gum/poly(acrylic acid) graft copolymer was separated from the polymerization
      medium, purified and subjected to crosslinking treatment, using alkaline
      epichlorohydrin as a crosslinking agent. Silver nitrate solution was added during
      the crosslinking treatment in varying concentrations, that the reaction
      conditions affect crosslinking of guar gum/poly(acrylic acid) graft copolymer to
      a hydrogel, as well as reduction of silver nitrate to silver nanoparticles,
      giving rise to the formation of silver/guar gum/poly(acrylic acid) nanocomposite.
      Factors affecting the grafting reaction as well as those affecting the
      crosslinking/reduction treatment were optimized. The so synthesized nanocomposite
      hydrogel samples were fully characterized, regarding their contents of silver
      nanoparticles and swelling ratio. The electrical conductivity of the
      nanocomposite hydrogel was studied and it was found to be affected by the
      swelling ratio of the hydrogel as well as its content of silver nanoparticles. 

PMID- 24928056
TI  - Calcium-activated chloride channels anoctamin 1 and 2 promote murine uterine
      smooth muscle contractility.
AB  - OBJECTIVE: To determine the presence of calcium activated chloride channels
      anoctamin 1 (ANO1) and 2 (ANO2) in human and murine uterine smooth muscle (MUSM)
      and evaluate the physiologic role for these ion channels in murine myometrial
      contractility. STUDY DESIGN: We performed reverse transcription polymerase chain
      reaction to determine whether ANO1 and 2 are expressed in human and murine
      uterine tissue to validate the study of this protein in mouse models.
      Immunohistochemical staining of ANO1 and 2 was then performed to determine
      protein expression in murine myometrial tissue. The function of ANO1 and 2 in
      murine uterine tissue was evaluated using electrophysiologic studies, organ bath,
      and calcium flux experiments. RESULTS: ANO1 and 2 are expressed in human and MUSM
      cells. Functional studies show that selective antagonism of these channels
      promotes relaxation of spontaneous MUSM contractions. Blockade of ANO1 and 2
      inhibits both agonist-induced and spontaneous transient inward currents and
      abolishes G-protein coupled receptor (oxytocin) mediated elevations in
      intracellular calcium. CONCLUSION: The calcium activated chloride channels ANO1
      and 2 are present in human and murine myometrial tissue and may provide novel
      potential therapeutic targets to achieve effective tocolysis.

PMID- 24928059
TI  - Patient satisfaction: opportunities for quality improvement.

PMID- 24928060
TI  - Re: "counterpoint: overdiagnosis in breast cancer screening".

PMID- 24928061
TI  - Are we Spain?

PMID- 24928062
TI  - Evaluation of the bioactivity of influenza vaccine strains in vitro suggests that
      the introduction of new strains in the 2010 Southern Hemisphere trivalent
      influenza vaccine is associated with adverse events.
AB  - In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there
      was an unexpected increase in post-marketing adverse event reports of febrile
      seizures (FS) in children under 5 years of age shortly after vaccination with the
      CSL trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs
      and other licensed 2010 SH TIVs. The present study describes the outcomes of a
      series of in vitro experiments directed at elucidating the root cause. The
      scientific investigations found that a subset of paediatric donors displayed
      elevated cytokine/chemokine responses to the CSL 2010 SH TIV but not to previous
      CSL TIVs nor other 2010 SH TIVs. The induction of elevated cytokines/chemokines
      in paediatric whole blood correlated with elevated NF-kappaB activation in a
      HEK293 cell reporter assay. The data indicate that the introduction of the
      B/Brisbane/60/2008 strain within the CSL manufacturing process (such as occurred
      in the preceding 2009/10 NH season) appears to have raised the pyrogenic
      potential of the CSL 2009/10 NH TIV but that this was insufficient to elicit FS
      in children <5 years. The 2010 SH season coincided with the first introduction of
      the H1N1 A/California/07/2009 in combination with the B/Brisbane/60/2008 strain.
      Our data demonstrates that the introduction of the H1N1 A/California/07/2009 (and
      to a much lesser degree, H3N2 A/Wisconsin/15/2009) in combination with
      B/Brisbane/60/2008 (as expressed through the CSL method of manufacture) combined
      and likely compounded the bioactivity of the CSL 2010 SH TIV. This was associated
      with stronger immune responses, which in a proportion of children <5 years were
      associated with FS. The assays and systems developed during these investigations
      should greatly assist in determining the bioactivity of new influenza strains,
      and thus aid with the manufacture of CSL TIVs indicated for use in the paediatric
      population. 

PMID- 24928063
TI  - Effect of Asian sand dust on Japanese cedar pollinosis.
AB  - OBJECTIVE: Asian sand dust (ASD), originating in the deserts of Mongolia and
      China, spreads over large areas and is associated with adverse effects on human
      health in East Asia, including asthma, heart disease, and some allergic diseases.
      However, the effect of ASD on patients with seasonal allergic rhinitis caused by
      Japanese cedar pollen (SAR-JCP), the most common form of allergic rhinitis,
      remains unclear. The aim of this study was to investigate the effect of ASD on
      SAR-JCP patients. METHODS: A total of 41 patients with SAR-JCP recorded nasal and
      ocular allergic symptom scores in a diary. We assessed the influence of ASD
      events on patients with SAR-JCP during the JCP season and before and after the
      JCP season. RESULTS: ASD events did not influence nasal and ocular allergy
      symptoms during the JCP season. Scores for sneezing and runny nose were
      significantly increased by ASD events in the pre-JCP season. Ocular symptom
      scores were significantly increased by ASD events in the post-JCP season.
      CONCLUSION: Our results suggest that ASD may exacerbate allergy symptoms even
      before mass scattering of JCP, which usually does not cause allergic symptoms in
      patients with SAR-JCP. ASD also induced conjunctivitis symptoms after the JCP
      season. However, we did not observe any adverse effects of ASD on allergic
      symptoms during the JCP season.

PMID- 24928064
TI  - Expression of claudin-3 in the esophagus and larynx of rat reflux model.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      laryngeal expression of claudin-3 and laryngopharyngeal reflux (LPR) in a rat
      reflux model. METHODS: Eight Wistar rats were divided into two groups. Four rats
      underwent total esophageal myectomy to induce reflux, and the remainder underwent
      a sham operation as a control. All animals were sacrificed 12 weeks after surgery
      to perform tissue histology and Western blot analysis. RESULTS: Lymphocyte
      infiltration increased significantly in the study group in both esophageal and
      laryngeal samples (P=0.001, 0.002, respectively). Both esophageal and laryngeal
      expressions of claudin-3 were significantly lower in the study group when
      compared with that in the control group (P=0.045, 0.037, respectively).
      CONCLUSION: The results of this study suggest that a decrease in claudin-3 could
      be a sensitive indicator of reflux laryngitis in rats.

PMID- 24928065
TI  - Relationship between positive bacterial culture in maxillary sinus and surgical
      outcomes in chronic rhinosinusitis with nasal polyps.
AB  - OBJECTIVES: There are many studies on clinical prognosis following endoscopic
      sinus surgery (ESS) for the treatment of chronic rhinosinusitis with nasal polyp
      (CRSwNP). However, there are no independent reports on bacterial infection as a
      factor that influences surgical outcomes. We investigated the association between
      bacterial infection and surgical outcomes following ESS. METHODS: This
      retrospective review of medical records was performed on 71 patients with CRSwNP
      that was refractory to medical treatment and who were diagnosed between July 2007
      and June 2012. The extent of the polyps and the Lund-Mackay CT score (L-M score)
      were preoperatively evaluated in all the patients. For this analysis, patients
      were classified into three groups (normal flora, culture-positive, and culture
      negative) according to their intraoperative bacterial culture results. We
      compared the objective endoscopic findings between these groups at 6-months
      postsurgery. RESULTS: Bacteria were cultured in 55 of the 71 patients (77%). Of
      these, 43 patients (61%) demonstrated endoscopic improvement at the 6-month
      follow-up examination. The preoperative L-M score and polyp grade demonstrated no
      significant statistical differences in terms of surgical outcome, but the cure
      rate was statistically higher in culture-negative patients in comparison with
      normal flora and culture-positive patients (87.5% vs. 46.2% vs. 54.8,
      respectively). CONCLUSION: Intraoperative culture results can be a prognostic
      factor for the clinical outcomes of ESS in CRSwNP patients. Hence, the
      intraoperative culturing of pathologic secretions and the postoperative
      administration of susceptible antibiotics could improve surgical results.

PMID- 24928066
TI  - Exploratory associations with tumor necrosis factor-alpha, disinhibition and
      suicidal endorsement after traumatic brain injury.
AB  - PURPOSE: To examine the relationship of Tumor Necrosis Factor (TNF)-alpha to
      disinhibition and suicidal endorsement after traumatic brain injury (TBI).
      PARTICIPANTS: Adults with moderate to severe TBI (acute serum levels: n=48, n=543
      samples; acute CSF levels: n=37, n=389 samples; chronic serum levels: n=48, n=326
      samples). MAIN MEASURES: TNFalpha levels (CSF, Serum) from time of injury to 12
      months post-injury; Frontal Systems Behavior Scale - Disinhibition Subscale at 6
      and 12 months post-injury; Patient Health Questionnaire at 6 and 12 months post
      injury. RESULTS: Participants with TBI had significantly higher CSF and serum
      TNFalpha levels than healthy controls (p<0.05). Acute and chronic serum TNFalpha
      was significantly associated with disinhibition at 6 months post-injury (p=0.009,
      p=0.029 respectively), and 6 month disinhibition was associated with suicidal
      endorsement at both 6 and 12 months (p=0.045, p=0.033 respectively) and
      disinhibition at 12 months post-injury (p<0.001). CONCLUSION: These preliminary
      data suggest a biological to behavioral pathway of suicidality after TBI, from
      TNFalpha to disinhibition to suicidal endorsement. Future investigation is
      warranted to validate these findings and clarify what biological mechanisms might
      underlie these relationships.

PMID- 24928067
TI  - Gut expansion and contraction in the predatory soil mite Pergamasus longicornis
      (Mesostigmata: Parasitidae): a stiff system.
AB  - Mite digestive processes are inferred from gut expansion and contraction time in
      the free-living predatory soil mite Pergamasus longicornis (Berlese), estimated
      using a temporal series of histological sections. Gut regions (bar the rectal
      vesicle) behave broadly in unison for rapid initial filling (ingestion half-life
      about 2-3 min; max 8 min), but behave heterogeneously when slowly emptying
      (digestion/egestion half-life from about 2-3 h; max 8.5 h). Anterior gut regions
      fill and empty the earliest. Posterior gut regions take the longest to fill and
      to empty. Switching first from filling-predominating to emptying-predominating in
      the gut occurs around 2 h from the start of feeding. Median time for the initial
      completion of gut filling and for the commencement of gut emptying is 10 min and
      12.5 h, respectively, from the start of feeding. Three phases of gut changes are
      critically discussed: rapid filling, concentration by fluid loss (via coxal
      glands), and slow emptying. Independent corroboration of coxal droplet formation
      is included. Predictions to confirm or refute postulated mechanisms of salivary,
      coxal or rectal water balance are given. Overall total gut filling (ingestion)
      plus gut emptying (digestion/egestion) time in this poikilotherm is approximately
      29-52.5 h (1+ - 2+ days) at room temperature from the start of feeding on large
      dipteran prey ([Formula: see text] gut emptyings per day). Pergamasus longicornis
      exhibits the stiff digestive system of an intermittent 'bolus' feeder.

PMID- 24928068
TI  - Towards plant wires.
AB  - In experimental laboratory studies we evaluate a possibility of making electrical
      wires from living plants. In scoping experiments we use lettuce seedlings as a
      prototype model of a plant wire. We approximate an electrical potential transfer
      function by applying direct current voltage to the lettuce seedlings and
      recording output voltage. We analyse oscillation frequencies of the output
      potential and assess noise immunity of the plant wires. Our findings will be used
      in future designs of self-growing wetware circuits and devices, and integration
      of plant-based electronic components into future and emergent bio-hybrid systems.

PMID- 24928069
TI  - An uncommon presentation of eosinophilic granulomatosis with polyangiitis: a case
      report.
AB  - INTRODUCTION: Eosinophilic granulomatosis with polyangiitis is a rare and
      potentially fatal disease if not readily diagnosed. Cerebral involvement is
      extremely rare and clinical presentation as hemorrhagic stroke is even rarer.
      CASE PRESENTATION: A 58-year-old Caucasian man was admitted to our medical unit
      because of a computed tomography-diagnosed hemorrhagic stroke with right-sided
      hemiparesis and fever. A chest computed tomography scan also revealed multiple
      bilateral pulmonary infiltrates; coronary artery, and carotid and left vertebral
      artery calcifications were also observed. Empiric antimicrobial therapy with
      cephalosporins was promptly undertaken; low-molecular-weight heparin was
      introduced as prophylaxis for venous thromboembolism. Over the following days,
      magnetic resonance imaging scans showed a regression of the hemorrhagic
      framework, also revealing hypoxic areas consistent with acute ischemic lesions.
      With a computed tomography scan showing a worsening of his pulmonary framework,
      antimicrobial therapy was modified and corticosteroids were introduced. A new
      blood cell count revealed further increased leukocytosis (17.49 * 10(3) MUL),
      characterized by a surprising rise of eosinophilic cells (32.8%). Angiography of
      the coronary arteries found diffuse dilatations with severe signs of endothelial
      damage. Such an unexpected framework induced a strong suspicion that the stroke
      was the expression of a systemic vasculitis, which had triggered his cerebral,
      coronary, and pulmonary frameworks. The search for antineutrophil cytoplasmic
      antibody was positive for perinuclear antineutrophil cytoplasmic antibody, and
      eosinophilic granulomatosis with polyangiitis was diagnosed. Explaining to the
      patient the rarity of his disease, and what the most typical presentations of
      eosinophilic granulomatosis with polyangiitis were, he revealed that before
      admission he had had scalp injuries, in the nuchal region, and had taken
      corticosteroids as self-medication, with subsequent disappearance of the lesions.
      Therefore, high-dose corticosteroid treatment was started, and at discharge he
      was in good clinical condition with a slight right-sided hyposthenia.
      CONCLUSIONS: A diagnosis of eosinophilic granulomatosis with polyangiitis is
      often difficult, but we are convinced that intake of corticosteroids on a self
      prescribed basis may have obscured the clinical presentation. Therefore, this
      case also suggests how the growing phenomenon of self-medication can be harmful,
      and that a careful investigation of clinical history is still an act of paramount
      importance.

PMID- 24928071
TI  - Special issue on photosynthesis research for sustainability.

PMID- 24928070
TI  - A human-specific allelic group of the MHC DRB1 gene in primates.
AB  - BACKGROUND: Diversity among human leukocyte antigen (HLA) molecules has been
      maintained by host-pathogen coevolution over a long period of time. Reflecting
      this diversity, the HLA loci are the most polymorphic in the human genome. One
      characteristic of HLA diversity is long-term persistence of allelic lineages,
      which causes trans-species polymorphisms to be shared among closely related
      species. Modern humans have disseminated across the world after their exodus from
      Africa, while chimpanzees have remained in Africa since the speciation event
      between humans and chimpanzees. It is thought that modern humans have recently
      acquired resistance to novel pathogens outside Africa. In the present study, we
      investigated HLA alleles that could contribute to this local adaptation in humans
      and also studied the contribution of natural selection to human evolution by
      using molecular data. RESULTS: Phylogenetic analysis of HLA-DRB1 genes identified
      two major groups, HLA Groups A and B. Group A formed a monophyletic clade
      distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a
      human-specific allelic group. Our estimates of divergence time suggested that
      seven HLA-DRB1 Group A allelic lineages in humans have been maintained since
      before the speciation event between humans and chimpanzees, while chimpanzees
      possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to
      Group A. Experimental data showed that some Group A alleles bound to peptides
      derived from human-specific pathogens. Of the Group A alleles, three exist at
      high frequencies in several local populations outside Africa. CONCLUSIONS: HLA
      Group A alleles are likely to have been retained in human lineages for a long
      period of time and have not expanded since the divergence of humans and
      chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have
      been lost in the chimpanzee due to differences in selective pressures. The
      presence of alleles with high frequency outside of Africa suggests these HLA
      molecules result from the local adaptations of humans. Our study helps elucidate
      the mechanism by which the human adaptive immune system has coevolved with
      pathogens over a long period of time.

PMID- 24928072
TI  - Energetic and nutritional constraints on infant brain development: implications
      for brain expansion during human evolution.
AB  - The human brain confronts two major challenges during its development: (i)
      meeting a very high energy requirement, and (ii) reliably accessing an adequate
      dietary source of specific brain selective nutrients needed for its structure and
      function. Implicitly, these energetic and nutritional constraints to normal brain
      development today would also have been constraints on human brain evolution. The
      energetic constraint was solved in large measure by the evolution in hominins of
      a unique and significant layer of body fat on the fetus starting during the third
      trimester of gestation. By providing fatty acids for ketone production that are
      needed as brain fuel, this fat layer supports the brain's high energy needs well
      into childhood. This fat layer also contains an important reserve of the brain
      selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other
      primates. Foremost amongst the brain selective minerals are iodine and iron, with
      zinc, copper and selenium also being important. A shore-based diet, i.e., fish,
      molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the
      richest known dietary sources of brain selective nutrients. Regular access to
      these foods by the early hominin lineage that evolved into humans would therefore
      have helped free the nutritional constraint on primate brain development and
      function. Inadequate dietary supply of brain selective nutrients still has a
      deleterious impact on human brain development on a global scale today,
      demonstrating the brain's ongoing vulnerability. The core of the shore-based
      paradigm of human brain evolution proposes that sustained access by certain
      groups of early Homo to freshwater and marine food resources would have helped
      surmount both the nutritional as well as the energetic constraints on mammalian
      brain development. 

PMID- 24928073
TI  - Validation of Hill-type muscle models in relation to neuromuscular recruitment
      and force-velocity properties: predicting patterns of in vivo muscle force.
AB  - We review here the use and reliability of Hill-type muscle models to predict
      muscle performance under varying conditions, ranging from in situ production of
      isometric force to in vivo dynamics of muscle length change and force in response
      to activation. Muscle models are frequently used in musculoskeletal simulations
      of movement, particularly when applied to studies of human motor performance in
      which surgically implanted transducers have limited use. Musculoskeletal
      simulations of different animal species also are being developed to evaluate
      comparative and evolutionary aspects of locomotor performance. However, such
      models are rarely validated against direct measures of fascicle strain or
      recordings of muscle-tendon force. Historically, Hill-type models simplify
      properties of whole muscle by scaling salient properties of single fibers to
      whole muscles, typically accounting for a muscle's architecture and series
      elasticity. Activation of the model's single contractile element (assigned the
      properties of homogenous fibers) is also simplified and is often based on
      temporal features of myoelectric (EMG) activation recorded from the muscle.
      Comparison of standard one-element models with a novel two-element model and with
      in situ and in vivo measures of EMG, fascicle strain, and force recorded from the
      gastrocnemius muscles of goats shows that a two-element Hill-type model, which
      allows independent recruitment of slow and fast units, better predicts temporal
      patterns of in situ and in vivo force. Recruitment patterns of slow/fast units
      based on wavelet decomposition of EMG activity in frequency-time space are
      generally correlated with the intensity spectra of the EMG signals, the strain
      rates of the fascicles, and the muscle-tendon forces measured in vivo, with
      faster units linked to greater strain rates and to more rapid forces. Using
      direct measures of muscle performance to further test Hill-type models, whether
      traditional or more complex, remains critical for establishing their accuracy and
      essential for verifying their applicability to scientific and clinical studies of
      musculoskeletal function. 

PMID- 24928074
TI  - Neurolymphomatosis: a case series of clinical manifestations, treatments, and
      outcomes.
AB  - BACKGROUND: Neurolymphomatosis (NL) is a rare clinical entity characterized by
      infiltration of malignant lymphocytes into the peripheral nervous system. We
      analyzed the clinicoradiological features, treatments, and outcomes in NL
      patients. METHODS: We identified six patients with NL seen at The University of
      Texas MD Anderson Cancer Center from 01/2010 to 10/2012. We extracted clinical
      presentations, imagings, CSF cytology, and electrodiagnostic studies from medical
      records. One patient had a nerve biopsy. We defined therapy response as clinical
      improvement of neurological deficits. FINDINGS: The mean age at onset was 57.1
      years. Most were predominantly men with non-Hodgkin lymphoma. Positron emission
      tomography (PET) was positive in five patients. Nerve conduction demonstrated
      mononeuritis multiplex, plexopathy, demyelination, and axonal
      polyradiculoneuropathy, whereas electromyography was nonspecific. All patients
      received systemic chemotherapy, four intrathecal chemotherapy, and three
      intravenous immunoglobulin, plasma exchange or both. One patient who received
      intravenous immunoglobulin showed mild neurological improvement. Two patients
      responded, and the median overall survival was 15 months. CONCLUSIONS: NL is an
      increasingly recognized complication of NHL and leukemia. A high clinical
      suspicion is necessary for correct diagnosis. In the present series, patients
      with leukemia had mononeuritis multiplex, whereas those with lymphoma had
      plexopathy. Electrodiagnosis and PET scans were useful diagnostic tools. No
      factors correlated with poorer prognosis. International collaborative studies
      will help to better determine the risk factors of NL, response to treatment and
      outcomes.

PMID- 24928075
TI  - Psychological distress after subarachnoid hemorrhage: patient support groups can
      help us better detect it.
AB  - INTRODUCTION: One-quarter of subarachnoid hemorrhage (SAH) survivors develop
      psychological distress. This impedes recovery. Limitations to existing care
      pathways mean that distress often goes undetected. We need to know how to better
      identify it. OBJECTIVES: Support groups for SAH exist in many countries. No
      research has been conducted on them. Distressed patients might be concentrated
      amongst them. If true, this could offer a low-cost way to help better identify
      distress. We conducted the first study to determine which survivors access such
      groups, their needs and compared them to the wider SAH population. METHODS: 414
      UK SAH survivors affiliated with national support groups were recruited. They
      completed a questionnaire, including validated measures of anxiety, depression
      and posttraumatic stress, and asked whether they had been examined or treated for
      distress post-SAH. Regression established factors associated with treatment.
      RESULTS: Participants' mean age at SAH was 44.6 and 312 (75%) were female. Most
      (68.4%) reported a cerebral aneurysm as their SAH's cause and were treated with
      coiling. Median years since SAH were three. Over three-quarters of participants
      were experiencing clinical distress. Regression found distressed participants
      were twice as likely to have been examined and treated for distress.
      Nevertheless, 47% of distressed participants had not been examined for distress
      post-SAH and 55% had not been offered treatment. CONCLUSION: Psychological
      distress is overrepresented amongst support groups. Members also tend to be
      younger and female. Establishing referral pathways from support groups to health
      systems might improve detection of distress and allow the benefits of improved
      survival from SAH to be fully realized.

PMID- 24928076
TI  - Paraneoplastic downbeat nystagmus associated with cerebellar hypermetabolism
      especially in the nodulus.
AB  - A 52-year-old man with vertigo and imbalance for two weeks showed spontaneous
      downbeat (DBN), horizontal gaze-evoked, and positional apogeotropic nystagmus
      along with severe limb and truncal ataxia. Gadolinium-enhanced brain MRI was
      normal, but whole body and brain 2-deoxy-2-[F18]fluoro-d-glucose-positron
      emission tomography revealed hypermetabolism in the right lower lobe of the lung
      and the cerebellum, especially in the nodulus. The lesion in the lung was
      confirmed as mixed cell carcinoma. Paraneoplastic DBN may be associated with
      cerebellar hypermetabolism, especially in the nodulus.

PMID- 24928077
TI  - Antisecretory factor (AF) exerts no effects on intracranial pressure (ICP) waves
      and ICP in patients with idiopathic normal pressure hydrocephalus and idiopathic
      intracranial hypertension.
AB  - BACKGROUND: Antisecretory factor (AF) and derivates thereof counteract brain
      edema and inflammation, and normalize ICP dynamics. The aim of the present study
      was to assess whether AF normalized the abnormal ICP waves, indicative of
      impaired intracranial compliance, seen in patients with idiopathic normal
      pressure hydrocephalus (iNPH) and idiopathic intracranial hypertension (IIH). The
      hypothesis was that brain swelling contributes to the abnormal ICP waves.
      METHODS: The study enrolled patients undergoing diagnostic ICP wave monitoring
      for either iNPH or IIH. The ICP waves and ICP were recorded continuously before
      and after oral administration of Salovum(r) (0.5 g/kg body weight/day divided by
      three doses), a freeze-dried egg yolk enriched in AF activity. Mean ICP wave
      amplitude (MWA), mean ICP wave rise time coefficient (MWRTC), and mean ICP were
      compared before and after Salovum(r) administration. RESULTS: A total of 10 iNPH
      patients and 8 IIH patients were included. No significant changes in the ICP wave
      indices or ICP were seen after Salovum(r) administration. Neither any significant
      time-dependent effect was observed. CONCLUSION: The lack of effect of Salovum(r)
      on ICP wave indices and ICP in iNPH and IIH may provide indirect evidence that
      brain swelling does not play a crucial role in the ICP wave indices or ICP of
      these conditions.

PMID- 24928078
TI  - A case of adult-onset reducing body myopathy presenting a novel clinical feature,
      asymmetrical involvement of the sternocleidomastoid and trapezius muscles.
AB  - We herein report a 32-year-old woman with adult-onset reducing body myopathy
      (RBM) who had a mutation in the four-and-a-half LIM domain 1 gene (FHL1) and
      showed a marked asymmetrical involvement of sternocleidomastoid and trapezius
      muscles. At 30 years of age she noticed bilateral foot drop, and over the next
      two years developed difficulty raising her right arm. At 32 years of age she was
      admitted to our hospital for a diagnostic evaluation. Neurological examination
      showed moderate weakness and atrophy of her right sternocleidomastoid muscle,
      right trapezius muscle, and bilateral upper proximal muscles. There were severe
      weakness and atrophy of her bilateral tibialis anterior muscles. Her deep tendon
      reflexes were hypoactive in her upper extremities. Her serum creatine kinase
      level was mildly increased. Muscle biopsy specimens from the left tibialis
      anterior muscle revealed marked variation in fiber size, some necrotic or
      regenerating fibers, and reducing bodies. Gene analysis of FHL1 demonstrated a
      mutation: a heterozygous missense mutation of c.377G>A (p. C126T) in FHL1.
      Compared with previous adult-onset RBM cases harboring mutations in FHL1, our
      case was characterized by asymmetrical atrophy of the sternocleidomastoid and
      trapezius muscles.

PMID- 24928079
TI  - Sudden death in Parkinson's disease: a retrospective autopsy study.
AB  - The aim of this paper is to reveal the causes of death and to verify sudden death
      of Parkinson's disease (PD) in an autopsy study. We reviewed the clinical data
      and the causes of death in 16 PD patients who had postmortem examinations. Prior
      to autopsy, nine patients died of known causes: five patients died of aspiration
      pneumonia, two of myocardial infarction, one of asphyxia, and one of dilated
      cardiomyopathy. Autopsy confirmed that the putative causes of death were
      compatible with the pathological ones. The remaining seven patients died suddenly
      of unknown causes. Autopsy revealed that the causes of death were asphyxia in two
      patients and perforation of a duodenal ulcer in one patient. Autopsy did not
      determine the causes of unknown death in the remaining four patients.
      Consequently, autopsy revealed that eight patients died of swallowing problems
      such as aspiration pneumonia and asphyxia, four of sudden death, three of cardiac
      problems, and one of a gastrointestinal problem. Although there was a bias that
      all patients had a postmortem examination, our study revealed that several PD
      patients died of sudden death without any satisfactory causes of death determined
      even by autopsy. Therefore, we propose that a non-negligible number of PD
      patients die of sudden death. 

PMID- 24928080
TI  - Natural course of LGI1 encephalitis: 3-5 years of follow-up without
      immunotherapy.
AB  - Antibodies against LGI1 (leucin-rich glioma-inactivated 1 protein) are associated
      with limbic encephalitis (LE), which is characterized by a favorable outcome
      following immunotherapy. Here, we present two cases, where antibodies against
      LGI1 were detected in the sera 36 and 53 months after acute LE, respectively, and
      none of the patients received immunotherapy. LE showed characteristics of LGI1
      encephalitis in both cases, including low sodium content in the sera;
      disorientation, hallucination, short-term memory loss; and epileptic seizures.
      One patient had faciobrachial tonic seizures. MRI indicated bilateral
      inflammation of the hippocampus in one case. We reviewed longitudinal clinical
      and MRI data covering 53 and 36 months after LE without immunotherapy,
      respectively. Both patients became seizure-free and spontaneously recovered with
      mild/moderate cognitive impairment. No relapses have been observed. Follow-up
      brain MRI indicated early hippocampal sclerosis and global brain atrophy in one
      case characterized by more pronounced cognitive deficit. Memory and verbal
      fluency were affected most during the natural course of LGI1 encephalitis. LGI1
      encephalitis had a monophasic course and spontaneously improved, suggesting that
      a relatively benign natural course may contribute to the favorable outcome
      observed after immunotherapy. Our data also indicate that LGI1 antibodies can be
      present in the sera without clinical disease activity.

PMID- 24928081
TI  - Tau protein, beta-amyloid1-42 and clusterin CSF levels in the differential
      diagnosis of Parkinsonian syndrome with dementia.
AB  - BACKGROUND: Parkinson's disease (PD), PD with dementia (PDD) and Lewy body
      dementia (DLB) are synucleinopathies. PDD and DLB are sometimes considered a
      transition between PD and Alzheimer dementia (AD). Finding in vivo markers or
      their combination could help in the differential diagnosis of these
      neurodegenerative (ND) diseases. OBJECTIVE: The aim of this study was to assess
      cerebrospinal fluid (CSF) levels of tau protein, betaamyloid1-42 and clusterin
      and to compare these levels among patients with probable PD, PDD, DLB and AD.
      METHODS: CSF levels of ND markers were assessed in 96 patients (27 patients with
      PD, 14 with PDD, 14 with DLB, 17 with AD and 24 subjects as a control group).
      RESULTS: In all of the groups of patients, beta-amyloid1-42 levels were
      decreasing in the order PD>PDD>DLB>AD, whereas tau protein and the tau
      protein/beta-amyloid1-42 index were increasing in the same order (PD<PDD<AD),
      except for DLB. In paired group comparisons, higher levels of clusterin in PD
      patients (p=0.005) and PDD patients (p=0.052) compared to the CG were found.
      CONCLUSION: The results of the present study support the role of clusterin in PD
      pathogenesis. The decreasing CSF beta-amyloid1-42 levels in the order PDD, DLB
      and AD may relate to the increasing presence of AD pathology in these disorders.

PMID- 24928082
TI  - Two cases of dural arteriovenous fistula presenting with parkinsonism and
      progressive cognitive dysfunction.
AB  - Dural arteriovenous fistula (DAVF) is a rare type of cerebral arteriovenous
      malformation. The occurrence of parkinsonism together with progressive cognitive
      dysfunction caused by DAVF has been rarely reported. The probable underlying
      pathophysiology could be due to venous hypertension caused by DAVF which leads to
      basal ganglia and cortical dysfunction. Here, two DAVF cases were reported
      presenting with parkinsonism and progressive cognitive dysfunction. A 54-year-old
      man (case 1) and a 75-year-old man (case 2) presented with bradykinesia, gait
      disturbances and cognitive dysfunction who were initially misdiagnosed as having
      Parkinson's disease. Case 1 exhibited a characteristic type of subcortical
      calcification on CT scan, while case 2 had specific resting tremor and
      intracranial hypertension. Both cases showed transient response to the
      dopaminergic treatment. After 3D time-of-flight (TOF) magnetic resonance
      arteriography (MRA) or digital subtraction arteriography (DSA), they were
      diagnosed as having DAVF. This report suggests the possibility of DAVF in
      patients presenting with parkinsonism and progressive cognitive dysfunction,
      which requires further attention to be paid, especially in those with transient
      response to levodopa. Early 3D TOF MRA or DSA is recommended for the diagnosis of
      DAVF. 

PMID- 24928084
TI  - The wide gulf between stage III and stage IV colon cancer.

PMID- 24928085
TI  - Disparity of anemia prevalence and associated factors among rural to urban
      migrant and the local children under two years old: a population based cross
      sectional study in Pinghu, China.
AB  - BACKGROUND: Number of internal rural to urban migrant children in China increased
      rapidly. The disparity of anemia prevalence among them and children of local
      permanent residents has been reported, both in big and middle-size cities. There
      has been no population-based study to explore the associated factors on feeding
      behaviors in small size cities of China. This study aimed to identify whether
      there was a difference in the prevalence of anemia between children of rural to
      urban migrant families and local children under 2 years old in a small coastal
      city in China, and to identify the associated factors of any observed difference.
      METHODS: A community-based, cross-sectional survey was conducted in Pinghu, a
      newly-developing city in Zhejiang Province, China, among the caregivers of 988
      children (667 who were identified as children of migrants and 321 locals) aged 6
      23 months. Disparity of anemia prevalence were reported. Association between
      anemia prevalence and socio-economic status and feeding behaviors were explored
      among two groups respectively. RESULTS: Anemia prevalence among the migrant and
      local children was 36.6% and 18.7% respectively (aPR 1.86, 95% CI 1. 40 to 2.47).
      Results from adjusted Poisson models revealed: having elder sibling/s were found
      as an associated factor of anemia with the aPR 1.47 (95% CI 1.16 to 1.87) among
      migrant children and 2.58 (95% CI 1.37 to 4.58) among local ones; anemia status
      was associated with continued breastfeeding at 6 months (aPR = 1.57, 95% CI 1.15
      to 2.14) and lack of iron-rich and/or iron-fortified foods (aPR = 0.68, 95% CI
      0.50 to 0.89) among the migrant children but not among local ones. CONCLUSION:
      Anemia was more prevalent among migrant children, especially those aged 6-11
      months. Dislike their local counterparts, migrant children were more vulnerable
      at early life and seemed sensitive to feeding behaviors, such as, over reliance
      on breastfeeding for nutrition after aged 6 months, lack of iron-rich and/or iron
      fortified foods. Future strategies to narrow the gap of anemia prevalence between
      the migrant and local children should target more susceptible groups and through
      improvement of feeding practices among younger children in those kinds of newly
      developing areas of China.

PMID- 24928086
TI  - Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous
      carcinoma cells.
AB  - BACKGROUND: Oral squamous cell carcinoma is an aggressive neoplasm with serious
      morbidity and mortality, which typically spreads through local invasive growth.
      Lysophosphatidic acid (LPA) is involved in a number of biological processes, and
      may have a role in cancer cell migration and invasiveness. LPA is present in most
      tissues and can activate cells through six different LPA receptors (LPAR1-6).
      Although LPA is predominantly promigratory, some of the receptors may have
      antimigratory effects in certain cells. The signalling mechanisms of LPA are not
      fully understood, and in oral carcinoma cells the specific receptors and pathways
      involved in LPA-stimulated migration are unknown. METHODS: The oral carcinoma
      cell lines E10, SCC-9, and D2 were investigated. Cell migration was studied in a
      scratch wound assay, and invasion was demonstrated in organotypic three
      dimensional co-cultures. Protein and mRNA expression of LPA receptors was studied
      with Western blotting and qRT-PCR. Activation of signalling proteins was examined
      with Western blotting and isoelectric focusing, and signalling mechanisms were
      further explored using pharmacological agents and siRNA directed at specific
      receptors and pathways. RESULTS: LPA stimulated cell migration in the two oral
      carcinoma cell lines E10 and SCC-9, but was slightly inhibitory in D2. The
      receptor expression profile and the effects of specific pharmacological
      antagonist and agonists indicated that LPA-stimulated cell migration was mediated
      through LPAR3 in E10 and SCC-9. Furthermore, in both these cell lines, the
      stimulation by LPA was dependent on PKC activity. However, while LPA induced
      transactivation of EGFR and the stimulated migration was blocked by EGFR
      inhibitors in E10 cells, LPA did not induce EGFR transactivation in SCC-9 cells.
      In D2 cells, LPA induced EGFR transactivation, but this was associated with
      slowing of a very high inherent migration rate in these cells. CONCLUSION: The
      results demonstrate LPA-stimulated migration in oral carcinoma cells through
      LPAR3, mediated further by PKC, which acts either in concert with or
      independently of EGFR transactivation.

PMID- 24928088
TI  - Neuroprotective role of BNIP3 under oxidative stress through autophagy in
      neuroblastoma cells.
AB  - Reactive oxygen species (ROS) are produced due to oxidative stress which has wide
      range of affiliation with different diseases including cancer, heart failure,
      diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's
      disease, ischemic and hemorrhagic diseases. This study shows the involvement of
      BNIP3 in the amplification of metabolic pathways related to cellular quality
      control and cellular self defence mechanism in the form of autophagy. We used
      conventional methods to induce autophagy by treating the cells with H2O2. MTT
      assay was performed to observe the cellular viability in stressed condition. MDC
      staining was carried out for detection of autophagosomes formation which
      confirmed the autophagy. Furthermore, expression of BNIP3 was validated by
      western blot analysis with LC3 antibody. From these results it is clear that
      BNIP3 plays a key role in defence mechanism by removing the misfolded proteins
      through autophagy. These results enhance the practical application of BNIP3 in
      neuroblastoma cells and are helpful in reducing the chances of neurodegenerative
      diseases. Although, the exact mode of action is still unknown but these findings
      unveil a molecular mechanism for the role of autophagy in cell death and provide
      insight into complex relationship between ROS and non-apoptotic programmed cell
      death. 

PMID- 24928087
TI  - Estrogen receptor alpha (ERS1) SNPs c454-397T>C (PvuII) and c454-351A>G (XbaI)
      are risk biomarkers for breast cancer development.
AB  - There are several risk factors related to Breast Cancer (BC) risks and response
      to chemotherapy with SERMs. Recently some single nucleotide polymorphisms (SNPs)
      on ESR1 gene have been associated to this disease. However, data are still
      inconclusive. The present study aimed to investigate the association of SNPs c454
      397T>C (also called PvuII) and c454-351A>G (so called XbaI) to incidence of
      sporadic BC; ERalpha expression in BC; tamoxifen hormonetherapy (HT-TMX)
      responsiveness. To do so, a cohort of BC patients was analyzed through
      retrospective data collection, immunohistochemistry to ERalpha protein, and
      genotyping for PvuII and XbaI SNPs by PCR-RFLP, confirmed by sequencing.
      Significant difference in PvuII alleles frequencies were found BC patients when
      compared to control samples. Patients with P allele have a 5.14-fold increased BC
      risk. We found higher P and X alleles frequencies in ERalpha positive BC and the
      pp and xx genotypes were observed exclusively in patients with HT-TMX-responsive
      BC. Taken together, data indicates that P allele as a novel sporadic BC biomarker
      whereas p and x alleles enhanced chemotherapy responsiveness. 

PMID- 24928089
TI  - Analysis of circulating microRNAs that are specifically increased in
      hyperlipidemic and/or hyperglycemic sera.
AB  - MicroRNAs (miRNAs) are small non-coding RNA sequences that regulate gene
      expression post-transcriptionally by translation inhibition or mRNA degradation.
      The aim of the present study was to analyze serum miRNAs modulated by
      hyperlipidemia and/or hyperglycemia and to correlate them with biochemical
      parameters within lipid metabolism. Five selected circulating miRNAs (miR-125a
      5p, miR-146a, miR-10a, miR-21 and miR-33a) were individually analyzed by TaqMan
      miRNA assays along with lipid and inflammation parameters in sera from 20
      hyperlipidemic (HL) and/or hyperglycemic (HG) patients, and compared with data
      from five normolipidemic/normoglycemic subjects. Results showed: (1) the levels
      of all the analyzed circulating miRNA were increased in HL sera and correlated
      positively with sera's lipid and inflammatory parameters; (2) circulating miR
      125a-5p and miR-146a levels were increased in HG and/or HL sera; (3) all selected
      miRNAs were detected in alpha-lipoprotein fraction from sera, and miR-33a was
      also present in beta-lipoprotein fraction; (4) miRNA concentrations were
      increased in the alpha-lipoprotein fraction from HL sera. These data show a
      statistically significant correlation of the analyzed miRNA with increased
      lipids, specifically with alpha- and beta-lipoproteins, and CRP and IL-1beta
      levels in HL and/or HG sera, suggesting a contribution of these miRNAs to the
      atherosclerotic process.

PMID- 24928091
TI  - Optimal decision making in heterogeneous and biased environments.
AB  - The issue of optimal performance in speeded two-choice tasks has played a
      substantial role in the development and evaluation of decision making theories.
      For difficulty-homogeneous environments, the means to achieve optimality are
      prescribed by the sequential probability ratio test (SPRT), or equivalently, by
      the drift diffusion model (DDM). Biases in the external environments are easily
      accommodated into these models by adopting a prior integration bias. However, for
      difficulty-heterogeneous environments, the issue is more elusive. I show that in
      such cases, the SPRT and the DDM are no longer equivalent and both are
      suboptimal. Optimality is achieved by a diffusion-like accumulation of evidence
      while adjusting the choice thresholds during the time course of a trial. In the
      second part of the paper, assuming that decisions are made according to the
      popular DDM, I show that optimal performance in biased environments mandates
      incorporating a dynamic-bias component (a shift in the drift threshold) in
      addition to the prior bias (a shift in the starting point) into the model. These
      conclusions support a conjecture by Hanks, Mazurek, Kiani, Hopp, and Shadlen,
      (The Journal of Neuroscience, 31(17), 6339-6352, 2011) and contradict a recent
      attempt to refute this conjecture by arguing that optimality is achieved with the
      aid of prior bias alone (van Ravenzwaaij et al., 2012). The psychological
      plausibility of such "mathematically optimal" strategies is discussed. The
      current paper contributes to the ongoing effort to understand optimal behavior in
      biased and heterogeneous environments and corrects prior conclusions with respect
      to optimality in such conditions. 

PMID- 24928092
TI  - Long-term semantic representations moderate the effect of attentional refreshing
      on episodic memory.
AB  - The McCabe effect (McCabe, Journal of Memory and Language 58:480-494, 2008)
      refers to an advantage in episodic memory (EM) retrieval for memoranda studied in
      complex span versus simple span tasks, particularly for memoranda presented in
      earlier serial positions. This finding has been attributed to the necessity to
      refresh memoranda during complex span tasks that, in turn, promotes content
      context binding in working memory (WM). Several frameworks have conceptualized WM
      as being embedded in long-term memory. Thus, refreshing may be less efficient
      when memoranda are not well-established in long-term semantic memory (SM). To
      investigate this, we presented words and nonwords in simple and complex span
      trials in order to manipulate the long-term semantic representations of the
      memoranda with the requirement to refresh the memoranda during WM. A recognition
      test was administered that required participants to make a remember-know decision
      for each memorandum recognized as old. The results replicated the McCabe effect,
      but only for words, and the beneficial effect of refreshing opportunities was
      exclusive to recollection. These results extend previous research by indicating
      that the predictive relationship between WM refreshing and long-term EM is
      specific to recollection and, furthermore, moderated by representations in long
      term SM. This supports the predictions of WM frameworks that espouse the
      importance of refreshing in content-context binding, but also those that view WM
      as being an activated subset of and, therefore, constrained by the contents of
      long-term memory. 

PMID- 24928083
TI  - Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients
      with resected stage III colon cancer (PETACC-8): an open-label, randomised phase
      3 trial.
AB  - BACKGROUND: Since the 1990s, fluorouracil-based adjuvant chemotherapy has
      significantly reduced the risk of tumour recurrence in patients with stage III
      colon cancer. We aimed to assess whether the addition of cetuximab to standard
      adjuvant oxaliplatin, fluorouracil, and leucovorin chemotherapy (FOLFOX4) in
      patients with stage III colon cancer improved disease-free survival (DFS).
      METHODS: For this open-label, randomised phase 3 study done in nine European
      countries, we enrolled patients through an interactive voice response system to
      the central randomisation centre, with a central stratified permuted block
      randomisation procedure. We randomly assigned patients with resected (R0) stage
      III disease (1:1) to receive 12 cycles of FOLFOX4 twice a week with or without
      cetuximab. Patients were stratified by N-status (N1 vs N2), T-status (T1-3 vs
      T4), and obstruction or perforation status (no obstruction and no perforation vs
      obstruction or perforation or both). A protocol amendment (applied in June, 2008,
      after 2096 patients had been randomly assigned to treatment-restricted enrolment
      to patients with tumours wild-type at codons 12 and 13 in exon 2 of the KRAS gene
      (KRAS exon 2 wild-type). The primary endpoint was DFS. Analysis was intention to
      treat in all patients with KRAS exon 2 wild-type tumours. The study is registered
      at EudraCT, number 2005-003463-23. FINDINGS: Between Dec 22, 2005, and Nov 5,
      2009, 2559 patients from 340 sites in Europe were randomly assigned. Of these
      patients, 1602 had KRAS exon 2 wild-type tumours (intention-to-treat population),
      791 in the FOLFOX4 plus cetuximab group and 811 in the FOLFOX4 group. Median
      follow-up was 3.3 years (IQR 3.2-3.4). In the experimental and control groups,
      DFS was similar in the intention-to-treat population (hazard ratio [HR] 1.05; 95%
      CI 0.85-1.29; p=0.66), and in patients with KRAS exon 2/BRAF wild-type (n=984, HR
      0.99; 95% CI 0.76-1.28) or KRAS exon 2-mutated tumours (n=742, HR 1.06; 95% CI
      0.82-1.37). We noted heterogeneous responses to the addition of cetuximab in
      preplanned subgroup analyses. Grade 3 or 4 acne-like rash (in 209 of 785 patients
      [27%] vs four of 805 [<1%]), diarrhoea (113 [14%] vs 70 [9%]), mucositis (63 [8%]
      vs 10 [1%]), and infusion-related reactions (55 [7%] vs 30 [4%]) were more
      frequent in patients treated with FOLFOX4 plus cetuximab than in those patients
      who received FOLFOX4 alone. INTERPRETATION: The addition of cetuximab to FOLFOX4
      did not improve DFS compared with FOLFOX4 alone in patients with KRAS exon 2 wild
      type resected stage III colon cancer. This trial cannot conclude on the benefit
      of cetuximab in the studied population, but the heterogeneity of response
      suggests that further investigation of the role of FOLFOX4 plus cetuximab in
      specific patient subgroups is warranted. FUNDING: Federation Francophone de
      Cancerologie Digestive (FFCD), Merck KGaA, and Sanofi-Aventis.

PMID- 24928093
TI  - Enhanced neutrophil extracellular trap generation in rheumatoid arthritis:
      analysis of underlying signal transduction pathways and potential diagnostic
      utility.
AB  - INTRODUCTION: Neutrophil extracellular traps (NETs) have recently been implicated
      in a number of autoimmune conditions, including rheumatoid arthritis (RA). We
      examined the underlying signaling pathways triggering enhanced NETosis in RA and
      ascertained whether the products of NETosis had diagnostic implications or
      usefulness. METHODS: Neutrophils were isolated from RA patients with active
      disease and from controls. Spontaneous NET formation from RA and control
      neutrophils was assessed in vitro with microscopy and enzyme-linked immunosorbent
      assay (ELISA) for NETosis-derived products. The analysis of the signal
      transduction cascade included reactive oxygen species (ROS) production,
      myeloperoxidase (MPO), neutrophil elastase (NE), peptidyl arginine deiminase 4
      (PAD4), and citrullinated histone 3 (citH3). NET formation was studied in
      response to serum and synovial fluid and immunoglobulin G (IgG) depleted and
      reconstituted serum. Serum was analyzed for NETosis-derived products, for which
      receiver operator characteristic (ROC) curves were calculated. RESULTS:
      Neutrophils from RA cases exhibited increased spontaneous NET formation in vitro,
      associated with elevated ROS production, enhanced NE and MPO expression, nuclear
      translocation of PAD4, PAD4-mediated citrullination of H3, and altered nuclear
      morphology. NET formation in both anti-citrullinated peptide antibody (ACPA)
      positive and -negative RA was abolished by IgG depletion, but restored only with
      ACPA-positive IgG. NETosis-derived products in RA serum demonstrated diagnostic
      potential, the ROC area under the curve for cell-free nucleosomes being >97%,
      with a sensitivity of 91% and a specificity of 92%. No significant difference was
      observed between ACPA-positive and -negative cases. CONCLUSIONS: Signaling
      elements associated with the extrusion of NETs are significantly enhanced to
      promote NETosis in RA compared with healthy controls. NETosis depended on the
      presence of ACPA in ACPA-positive RA serum. The quantitation of NETosis-derived
      products, such as cell-free nucleosomes in serum, may be a useful complementary
      tool to discriminate between healthy controls and RA cases.

PMID- 24928094
TI  - Organochlorine pesticide level differences among female inhabitants from
      Veracruz, Puebla and Tabasco, Mexico.
AB  - Organochlorine pesticides have been used in Mexico in malaria control programs
      and against ectoparasites. The objective of this study was to compare the levels
      of organochlorine pesticides: HCB, alpha-beta-gamma-HCH, pp'-DDE, op'-DDT and pp'
      DDT in adipose tissue of female inhabitants from three Mexican states: Veracruz,
      Puebla and Tabasco. Data analyses indicated higher beta-HCH levels in Puebla
      inhabitants. When comparing the mean values of the pp'-DDE concentrations among
      the three states, no statistically significant differences were noted. A trend of
      increasing concentrations of op'-DDT from Veracruz to Puebla and Tabasco was
      observed. Significantly higher pp'-DDT concentrations in Veracruz as compared to
      Puebla and Tabasco were determined. Using factorial analysis of three age
      categories (>30, 31-50, <51) organochlorine pesticide concentrations increases
      with age of participants, indicating time of exposure as a principal factor of
      organochlorine pesticides accumulation in adipose tissue. 

PMID- 24928095
TI  - Government says Public Health England should challenge it over health issues when
      necessary.

PMID- 24928096
TI  - Diabetes and oral implant failure: a systematic review.
AB  - The aim of this systematic review and meta-analysis was to investigate whether
      there are any effects of diabetes mellitus on implant failure rates,
      postoperative infections, and marginal bone loss. An electronic search without
      time or language restrictions was undertaken in March 2014. The present review
      followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines. Eligibility criteria included clinical human studies. The
      search strategy resulted in 14 publications. The I (2) statistic was used to
      express the percentage of total variation across studies due to heterogeneity.
      The inverse variance method was used for the random effects model when
      heterogeneity was detected or for the fixed effects model when heterogeneity was
      not detected. The estimates of an intervention for dichotomous outcomes were
      expressed in risk ratio and in mean difference in millimeters for continuous
      outcomes, both with a 95% confidence interval. There was a statistically
      significant difference (p = .001; mean difference = 0.20, 95% confidence interval
      = 0.08, 0.31) between diabetic and non-diabetic patients concerning marginal bone
      loss, favoring non-diabetic patients. A meta-analysis was not possible for
      postoperative infections. The difference between the patients (diabetic vs. non
      diabetic) did not significantly affect implant failure rates (p = .65), with a
      risk ratio of 1.07 (95% confidence interval = 0.80, 1.44). Studies are lacking
      that include both patient types, with larger sample sizes, and that report the
      outcome data separately for each group. The results of the present meta-analysis
      should be interpreted with caution because of the presence of uncontrolled
      confounding factors in the included studies. 

PMID- 24928097
TI  - Reactionary Dentinogenesis and Neuroimmune Response in Dental Caries.
AB  - Reactionary dentin formation is an adaptive secretory response mediated by
      odontoblasts to moderate dentin injury. The implications of this process for
      neuroimmune interactions operating to contain pathogens have not been fully
      appreciated. The purpose of the present study was to describe the relationship
      between reactionary dentinogenesis, the neurogenic changes of dental pulp
      innervation, and dendritic cell recruitment to caries progression, using a
      comparative immunohistochemical approach in human teeth from young adult
      individuals. Reactionary dentin formation during dentin caries progression is
      associated with changes in the integrity of junctional complexes within the
      odontoblast layer. Diminished coexpression of Cx43 and zonula occludens 1 implies
      a reduced level of intercellular connectivity between odontoblasts. Dentin caries
      also causes overexpression of growth-associated protein 43, a modulator of neural
      plasticity that promotes extensive sprouting of nerve endings into the
      reactionary dentin matrix. At the same time, an elevated number of HLA-DR
      positive dendritic cells infiltrate the odontoblast layer and subsequently invade
      reactionary dentin formed underneath the early caries-affected regions.
      Simultaneous odontoblast layer remodeling, nerve fiber sprouting, and activation
      of dendritic cells during caries progression suggest a coordinated neuroimmune
      response to fight caries pathogen invasion and to promote dentin-pulp healing. We
      propose that reactionary dentin formation hinders pathogen invasion and supports
      defensive neuroimmune interactions against infection. The eventual understanding
      of this complex scenario may contribute to the development of novel approaches to
      dental caries treatment. 

PMID- 24928098
TI  - The human miRNA repertoire of different blood compounds.
AB  - BACKGROUND: MiRNAs from body fluids gain more and more attraction as biomarker
      candidates. Besides serum, patterns from whole blood are increasingly considered
      as markers for human pathologies. Usually, the contribution of different cell
      types to the respective signature remains however unknown. In this study we
      provide insights into the human miRNome of different compounds of the blood
      including CD3, CD14, CD15, CD19, CD56 positive cells as well as exosomes.
      METHODS: We measured the miRNA repertoire for each cell type and whole blood for
      two individuals at three time points over the course of one year in order to
      provide evidence that the cell type miRNomes can be reproducibly detected.
      RESULTS: For measurements repeated after 24 hours we found on average correlation
      of 0.97, even after one year profiles still correlated with 0.96, demonstrating
      the enormous stability of the cell type specific miRNomes. Highest correlation
      was found for CD15 positive cells, exceeding Pearson correlation of 0.99. For
      exosomes a significantly higher variability of miRNA expression was detected. In
      order to estimate the complexity and variability of the cell type specific
      miRNomes, we generated profiles for all considered cell types in a total of seven
      unaffected individuals. While CD15 positive cells showed the most complex miRNome
      consisting of 328 miRNAs, we detected significantly less miRNAs (186, p = 1.5*10(
      5)) in CD19 positive cells. Moreover, our analysis showed functional enrichment
      in many relevant categories such as onco-miRNAs and tumor miRNA suppressors.
      Interestingly, exosomes were enriched just for onco-miRNAs but not for miRNA
      tumor suppressors. CONCLUSION: In sum, our results provide evidence that blood
      cell type specific miRNomes are very consistent between individuals and over
      time.

PMID- 24928099
TI  - Transcatheter closure of a pulmonary arteriovenous malformation in a patient with
      hereditary hemorrhagic telangiectasia.
AB  - Pulmonary arteriovenous malformations (PAVM) are rare pulmonary vascular
      anomalies. Over 50 % of the cases are associated with hereditary hemorrhagic
      telangiectasia or Osler-Weber-Rendu Syndrome. Untreated PAVMs progressively
      enlarge and can cause significant right-to-left shunting. Surgical- and catheter
      based approaches have been used in the management of PAVM. We report a case of a
      74-year-old man who presented with dyspnea and hypoxia and was found to have a
      large right-sided PAVM. He underwent percutaneous closure of the PAVM with an
      Amplatzer device with significant improvement of his symptoms. 

PMID- 24928100
TI  - Time Course of Calcium Concentrations and Risk Factors for Hypocalcemia in
      Patients Receiving Denosumab for the Treatment of Bone Metastases From Cancer.
AB  - BACKGROUND: Severe hypocalcemia sometimes develops during denosumab treatment for
      bone metastases from cancer and is, therefore, an important issue. However,
      limited information is available on the risk factors for hypocalcemia and the
      appropriate interval for monitoring serum calcium concentration. OBJECTIVE: The
      present study aimed to identify the risk factors for grade >=2 hypocalcemia and
      to investigate the time course of serum calcium concentrations in patients
      receiving denosumab for bone metastases from cancer. METHOD: The medical records
      of 66 cancer patients treated with denosumab between April 2012 and August 2013
      were retrospectively reviewed. RESULT: Of the 66 enrolled patients, 11, 5, and 1
      developed grade 1, 2, and 3 hypocalcemia, respectively. All 4 patients with a
      baseline estimated glomerular filtration rate (eGFR) of <30 mL/min developed
      hypocalcemia. Hypocalcemia occurred in only 20%, 24%, and 15% of patients with an
      eGFR of 30 to 59, 60 to 89, and >=90 mL/min, respectively. Multivariate logistic
      regression analysis revealed that lower eGFR values (odds ratio, 1.72 per 10
      mL/min decrease, P = 0.02) were significantly associated with grade >=2
      hypocalcemia. In 11 patients who developed hypocalcemia during the first
      treatment course, the mean calcium concentrations decreased from 9.8 mg/dL at
      baseline to 8.4 mg/dL during the first week and reached a nadir of 8.1 mg/dL
      during the second week. CONCLUSION: Our results support more frequent monitoring
      of serum calcium concentrations at baseline and during the first 2 weeks of
      treatment in patients receiving denosumab, especially those with an eGFR <30
      mL/min.

PMID- 24928101
TI  - Association of deep-vein thrombosis (DVT) with missed doses of prophylactic
      antithrombotic medications in ICU patients: a case-control study.
AB  - BACKGROUND: Medications for prevention of venous thromboembolism (VTE) are
      routinely prescribed in critically ill patients. OBJECTIVE: To identify any
      association between missed doses of VTE prophylaxis medications and acute, in
      hospital deep-vein thrombosis (DVT). METHODS: Case-control study in hospitalized
      adult patients at high risk for developing VTE, defined as an ICU length of stay
      (LOS) of at least 24 hours. Cases were defined as patients with acute DVT during
      hospitalization, and controls were patients with no documented DVT. Multivariate
      logistic regression was used to assess the odds of acute DVT in patients with any
      missed dose of prophylactic antithrombotic medication. RESULTS: Of 920 patients,
      59 (6.4%) experienced an acute, in-hospital DVT. Overall, 64% of patients missed
      at least 1 dose of VTE prophylaxis medication, and 33% missed more than 3 doses.
      In the univariate analysis, there was no significant association between any
      missed dose of prophylaxis medication and acute DVT (odds ratio [OR] = 0.96; CI =
      0.56-1.7). Multivariate logistic regression modeling confirmed no association
      between missed doses of pharmacological VTE medications and acute DVT (OR = 0.69
      [0.39-1.2]; P = 0.21). Prolonged hospital LOS was associated with increased odds
      of acute DVT (LOS = 4-6 days; OR = 0.75 [0.21-2.6]; LOS = 7-13 days; OR = 2.3
      [0.9-5.9]; and LOS = >=14 days; OR = 6.4 [2.6-15.9]). CONCLUSION: We found no
      evidence of a relationship between any missed dose of prophylactic antithrombotic
      medication and development of acute DVT. The odds of acute DVT increased in
      patients with prolonged hospital LOS.

PMID- 24928102
TI  - Comparison of Glucose Measures in Patients Receiving Concomitant Paroxetine and
      Pravastatin to Other SSRI/Statin Combinations.
AB  - BACKGROUND: An analysis of the US Food and Drug Administration's Adverse Event
      Reporting System database found evidence suggesting that the combination of the
      cholesterol-lowering drug pravastatin and the antidepressant paroxetine, produced
      a significant increase in average blood glucose measures. OBJECTIVE: Our intent
      was to investigate the reproducibility of these findings by conducting a similar
      analysis of administrative and prescription claims data from patients receiving
      primary care at the Palo Alto Medical Foundation. METHOD: We conducted an
      observational, retrospective review of 2149 adult patient records to compare mean
      measures of blood glucose between groups receiving concomitant paroxetine and
      pravastatin with the pooled means of those receiving 19 different combinations of
      a statin and a selective serotonin reuptake inhibitor (SSRI) antidepressant.
      Analysis of covariance (ANCOVA) was used to compare random glucose, fasting
      glucose, and glycosylated hemoglobin mean values, while adjusting for the
      covariates of age, gender, body mass index, and weight in patients with and
      without a diagnosis of diabetes mellitus. RESULT: A total of 65 observations were
      analyzed from patients receiving concomitant paroxetine and pravastatin and 2084
      from those receiving 19 other statin-SSRI pairs. The ANCOVA showed that
      significant covariate relationships included the diagnosis of diabetes mellitus,
      male gender, and body weight. After adjusting for covariates, no significant
      difference was found between the 3 mean glucose measures of the pravastatin
      paroxetine pair groups and the corresponding means of the pooled statin-SSRI pair
      groups (P > 0.05). CONCLUSION: Outpatients receiving concomitant pravastatin and
      paroxetine did not have significantly different mean glucose measures as compared
      with those receiving other statin-SSRI drug combinations.

PMID- 24928103
TI  - Paclitaxel-Induced Fingerprints Loss.

PMID- 24928104
TI  - Association of 24 bp duplication of human CHIT1 gene with asthma in a
      heterozygous population of north India: a case-control study.
AB  - PURPOSE: CHIT1 is expressed by pulmonary macrophages, which is typically the site
      of entry for many environmental fungi that may increase the risk of pulmonary
      fungal infection and lead to hypersensitivity. The conserved expression of this
      gene in humans suggests its physiological importance in the mammalian lung.
      METHODS: The present study was conducted with a total of 964 subjects, including
      483 healthy controls and 481 asthma patients. DNA samples were extracted from
      blood, and the genotyping was done using polymerase chain reaction method.
      RESULTS: Statistical analysis revealed that the 24 bp duplication in CHIT1 gene
      polymorphism shows highly significant association in heterozygous (wild/dup)
      genotype with OR 1.74, 95 % CI (1.29-2.36), and p = 0.000. However, the
      homozygous mutant genotype (dup/dup) was found to be non-significant with OR
      1.06, 95% CI (0.69-1.63), and p = 0.786. The combination of both wild/dup and
      dup/dup was also found to be highly significant with OR 1.57, 95% CI (1.18-2.11),
      and p = 0.002. CONCLUSIONS: This is the first study conducted in India which
      reports a significant association between 24 bp duplication in CHIT1 gene
      polymorphism and asthma in the studied North Indian population.

PMID- 24928105
TI  - Types of food and nutrient intake in India: a literature review.
AB  - Nowadays India is undergoing an impressive economic growth accompanied by a very
      slow decline, almost stagnation, in malnutrition levels. In developing countries,
      studies on dietary patterns and their relationship with nutritional status are
      scarce. Over the years some nutritional studies have been performed to explore
      different types of food consumed in various Indian regions, among different
      social samples. The aim of the present paper is to review and describe trends in
      food and nutrition intake patterns in the different states of India. The review
      was carried out in PubMed, using the advanced research criteria: [food* OR ("meal
      pattern*") OR ("eating pattern*")] AND ("nutrient intake") AND India*. PubMed
      research gave back 84 results and out of these, 7 papers due to their focus on
      food intake and consumption levels in India have been included in this study.
      Food intake patterns showed that most of the Indians are vegetarians and that
      food items rich in micronutrients (pulses, other vegetables, fruits, nuts,
      oilseeds and animal foods) are generally consumed less frequently. Poor and
      monotonous cereals-based diet may promote inadequate nutrition intakes according
      to Recommended Daily Allowance (RDA) standards. 

PMID- 24928106
TI  - Current status of NICUs in India: a nationwide survey and the way forward.
AB  - The number of Neonatal Intensive Care Units (NICUs) and Special Care Newborn
      Units (SCNUs) in the country has increased exponentially. However, their current
      status of functioning is not known. A structured questionnaire survey of 70 NICUs
      spread across the country was conducted to assess their infrastructure, staffing,
      equipment, patient profile and their involvement in research and training.
      Majority of the units were well staffed and led by neonatologists trained in
      India and abroad. All had facilities for mechanical ventilation and were equipped
      with sophisticated imported equipment. Yet, availability of in-house blood gas
      and X-ray, microbiology facility, invasive blood pressure monitoring and support
      of ophthalmologist was not universal. More than half had published papers in
      scientific journals and were having recognized training programs in neonatology.
      Though tremendous progress is visible since the last surveys, the number of NICUs
      is still grossly insufficient. The current and future gap in trained manpower is
      however daunting, and intensive efforts for expanding the in-service training
      programs and innovative approaches to training are required. There is an urgent
      need to improve the quality of care by launching collaborative quality
      improvement programs and mandatory periodic accreditation managed by independent
      empowered organizations. The focus has to move forward from simply 'survival till
      discharge' to 'intact complete life survival'. Simultaneously, the NICU care has
      to stay available and affordable for the masses.

PMID- 24928107
TI  - Occult HBV infection in multi transfused thalassemia patients.
AB  - OBJECTIVE: To determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C
      virus (HCV) infection in multitransfused thalassemic patients, with an aim to
      further highlight the need for donor screening strategy with supplementary
      molecular diagnostic tools for high risk population. METHODS: The study was
      conducted in 174 thalassemic subjects from Thalassemia unit of Central Red Cross
      Blood Bank, Cuttack, Odisha, India. Sero molecular diagnosis was followed to
      detect antigen, antibody and DNA in the study subjects. RESULTS: Prevalence of
      antibody to Hepatitis C, HBsAg, Anti HBs and Anti HBc were found to be 3.4 %, 0.5
      %, 30.4 % and 21.8 % respectively. HBV seropositivity increased with increase in
      number of transfusions. Anti HBc was 12 %, 26.8 % and 71.4 % in subjects who
      received <40, 40-80 and >80 units of transfusions respectively. HBV DNA was
      detected in 50 % (3/6) of subjects having anti HBc as the only marker (Occult HBV
      infection). More so, it was detected in 16.12 % (5/31) of cases who were sero
      positive for both Anti HBs and Anti HBc. CONCLUSIONS: These results indicate that
      thalassemic subjects need detailed screening of transfusion products. Fifty
      percent of occult HBV infection is a major concern suggesting inclusion of viral
      DNA amplification test along with antigen/antibody detection.

PMID- 24928108
TI  - Panoramic radiography and cone-beam computed tomography findings in preoperative
      examination of impacted mandibular third molars.
AB  - BACKGROUND: Preoperative radiographic examination of impacted mandibular third
      molars (IMTM) is essential to prevent inferior alveolar nerve injury during
      extraction. The purpose of this study was to evaluate the correlation between
      cone-beam computed tomography (CBCT) and digital panoramic radiography (DPR)
      findings in preoperative examination of IMTM. METHODS: This retrospective study
      included 298 teeth in 191 individuals. The relationship between the inferior
      alveolar canal (IAC) and the IMTM (buccal, lingual, interradicular or inferior),
      the position of the IMTM with respect to the IAC (contact, no contact), the
      morphologic shape of the mandible in the IMTM region (round, lingual extended,
      lingual concave), the type of IMTM (vertical, horizontal or angular) and the
      number of roots of the IMTM were evaluated on CBCT images. DPR images were
      evaluated for the number of roots of the IMTM and for the most common
      radiographic findings indicating a relationship between the IAC and the IMTM
      (darkening of the roots, diversion of the IAC, narrowing of the IAC and
      interruption of the white line). Data were statistically analyzed with Cramer V
      coefficient, Kappa statistic, chi-square and Fisher's exact test. RESULTS: There
      was a significant difference in number of roots detected on DPR versus CBCT
      images. There was a significant association between the type of IMTM and the
      morphologic shape of the mandible on CBCT images. Darkening of the roots and
      interruption of the white line on DPR images were significantly associated with
      the presence of contact between the IMTM and the IAC on CBCT images. CONCLUSIONS:
      Panoramic radiography is inadequate, whereas CBCT is useful to detect multiple
      roots of IMTM. When darkening of the roots and interruption of the white line are
      observed on panoramic images, there is increased likelihood of contact between
      the IMTM and the IAC. CBCT is required in these cases.

PMID- 24928109
TI  - Intestinal obstruction due to dual gastrointestinal atresia in infants: diagnosis
      and management of 3 cases.
AB  - BACKGROUND: Several types of congenital lesions can cause complete or incomplete
      obstruction of the intestine. Our purpose is to present 3 neonates with dual
      intestinal type I atresia, i.e., simultaneous obstructive lesions at 2 locations
      in which the atresia manifested as diaphragm-like tissue. CASE PRESENTATION: All
      3 cases were female infants ranging in age from 2 to 14 months. The common
      symptom in all cases was intermittent persistent vomiting. In some cases the
      vomitus was bilious, and other symptoms included abdominal distention and delayed
      meconium passage. Prior surgeries at another hospital were unsuccessful at
      relieving the symptoms in one case. One case had dual lesions in the colon, one
      dual lesions in the duodenum, and one atresia at both the distal portion of the
      ileum and the descending colon. Surgical exploration and removal of the lesions
      at our hospital was successful in all cases, and the infants were discharged in
      good condition. CONCLUSIONS: Type I atresia can manifest as a diaphragm-like
      tissue obstructing the continuity of gastrointestinal tract, and in rare cases
      multiple areas may be present. Base on the intermittent nature of the associated
      symptoms, diagnosis can be difficult and is often delayed. Physicians should be
      aware of this condition during the work-up of an infant with persistent
      intermittent vomiting.

PMID- 24928112
TI  - Analytical chemistry and the Chemical Weapons Convention.

PMID- 24928110
TI  - Adherence inhibition of Cronobacter sakazakii to intestinal epithelial cells by
      lactoferrin.
AB  - Cronobacter sakazakii is now recognized as an opportunistic pathogen and has been
      implicated in rare but severe cases of necrotizing enterocolitis, meningitis, and
      sepsis in neonates. The first step in bacterial pathogenesis requires that the
      organism adheres to host cells surfaces; therefore, agents that inhibit adherence
      might be useful for preventing infections. Lactoferrin, an iron binding protein
      found in milk, has been shown to inhibit bacterial adherence by direct
      interaction and disruption of bacterial surfaces. Therefore, the goal of this
      research was to assess the ability of two different types of bovine lactoferrin,
      alone and in combination with a 1:1 blend of galactooligosaccharides and
      polydextrose, to inhibit adherence of C. sakazakii to a HEp-2 human cell line.
      Results showed that the adherence of C. sakazakii was significantly reduced at a
      minimum lactoferrin concentration of 10 mg/ml. However, in combination with the
      oligosaccharide blend, no synergistic effect was observed in adherence
      inhibition. These results suggest that lactoferrin might interact with C.
      sakazakii and directly inhibit adhesion to tissue culture cells. 

PMID- 24928113
TI  - Development and validation of an ELISA kit for the detection of ricin toxins from
      biological specimens and environmental samples.
AB  - Ricin is a toxin that can be easily extracted from seeds of Ricinus communis
      plants. Ricin is considered to be a major bio-threat as it can be freely and
      easily acquired in large quantities. A deliberate release of such toxin in
      civilian populations would very likely overwhelm existing public health systems,
      resulting in public fear and social unrest. There is currently no commercially
      available or FDA-approved prophylaxis such as vaccines, or therapeutic antitoxins
      or antidotes, available for ricin intoxication. Patient treatment is typically
      supportive care based on symptoms, often designed to reinforce the body's natural
      response. This paper describes the development and validation of a robust ELISA
      test kit, which can be used to screen for ricin in biological specimens such as
      whole blood and faeces. Faecal specimens are shown in this study to have better
      diagnostic sensitivity and a wider diagnostic window compared to whole blood.
      From these results, it is concluded that faeces is the most suitable clinical
      specimen for diagnosis of ricin poisoning via the oral route. The ELISA test kit
      can also detect ricin in environmental samples. An advantage of this ELISA kit
      over other commercial off-the-shelf (COTS) detection kits currently on the market
      that are developed to screen environmental samples only is its ability to
      diagnose ricin poisoning from clinical specimens as well as detect ricin from
      environmental samples. 

PMID- 24928114
TI  - Model system for targeted drug release triggered by immune-specific signals.
AB  - A new sense-and-act system was realized by integrating a biocatalytic/bioaffinity
      electrode responding to immune signals represented by an antibody and a polymer
      modified electrode loaded with drug-mimicking species. The release of the drug
      mimicking species was achieved specifically in response to a signal antibody,
      thus demonstrating for the first time an immune-induced drug-releasing process.
      The present approach promises new options for future applications in controlled
      drug release and personalized medicine. 

PMID- 24928115
TI  - A new ELISA for the quantification of equine procalcitonin in plasma as potential
      inflammation biomarker in horses.
AB  - In human medicine, procalcitonin (PCT) is a very common and well-established
      biomarker for sepsis. Even though sepsis is also a leading cause of death in
      foals and adult horses, up to now, no data about the role of equine PCT in septic
      horses has been available. Based on monoclonal antibodies targeted against human
      PCT, we report here the development of a sandwich ELISA for the quantification of
      equine PCT in equine plasma samples. The ELISA was characterized for intra- and
      interassay variance and a working range from 25 to 1,000 ng mL(-1) was defined as
      within this range; both intra- and interassay variances were below 15 %. The
      target recovery ranged between 73 and 106 %. The ELISA was used to determine the
      equine PCT concentration in 24 healthy and 5 septic horses to show the potential
      for clinical evaluation of equine PCT. Significantly different (P = 0.0006) mean
      equine PCT concentrations were found for the healthy control group and the sepsis
      group (47 and 8,450 ng mL(-1)). 

PMID- 24928116
TI  - Determination of Tuta absoluta pheromones in water and tomato samples by
      headspace-gas chromatography-mass spectrometry.
AB  - Tuta absoluta is a tomato pest which is originally from South America. This pest
      was detected in eastern Spain in 2006 and it rapidly invaded various European
      countries and spread throughout the Mediterranean basin. The usual detection of
      this pest is based on the physical evaluation of the crops and in the exhaustive
      count of potential insects in dedicated traps. The early detection of that pest
      on the basis of more objective or measurable indicators is desirable. In this
      case, the combination of headspace and gas chromatography with mass spectrometric
      detection is proposed for the identification of Tuta absoluta pest using two of
      its pheromone components as markers. These components, namely: (3E,8Z,11Z)
      tetradecatrien-1-yl acetate and (3E,8Z)-tetradecadien-1-yl acetate, are
      characteristic of Tuta absoluta and they are not present in other insect
      pheromones. The developed combination allows the determination of both components
      in water and tomato samples with limits of detection in the range from 25-32 ng/L
      to 89-111 ng/kg, respectively. The precision, expressed as relative standard
      deviation, was better than 4.6% for water samples and better than 7.1% when
      tomato samples were analyzed. The relative recovery values varied in the interval
      94-100 and 83-99% for water and tomato samples.

PMID- 24928117
TI  - Active and progressive: a new duality of MS classification.

PMID- 24928118
TI  - Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma.
AB  - OBJECTIVES: To investigate the relevance of bevacizumab (BEV)-induced diffusion
      restricted lesions and T1-hyperintense lesions in patients with recurrent
      glioblastoma. METHODS: We prospectively screened 74 BEV-treated patients with
      recurrent glioblastoma for (1) diffusion-restricted lesions and/or, (2) lesions
      with a hyperintense signal on precontrast T1-weighted images. We further
      evaluated overall survival (OS), histopathology of the lesions, and patterns of
      progression. RESULTS: Twenty-five of 74 patients (34%) developed T1-hyperintense
      lesions, whereas diffusion-restricted lesions could be detected in 35 of 74
      patients (47%). In 21 of 74 patients (28%), the lesions displayed both features
      ("double-positive"). OS for patients with double-positive lesions was 13.0
      months; patients with neither of these lesions had an OS of 6.6 months (p <
      0.005). Histologic evaluation of double-positive lesions revealed extensive
      calcified necrosis in 4 of 4 patients. Notably, these double-positive lesions
      were rarely involved in further tumor progression. However, they were associated
      with an increase in distant recurrences at BEV failure. CONCLUSIONS: BEV-induced
      double-positive MRI lesions are a predictive imaging marker associated with a
      substantial survival benefit and with improved local control in patients with
      recurrent glioblastoma. Our data suggest that these lesions are the result of a
      sustained focal antitumor activity of BEV.

PMID- 24928119
TI  - Ataxia plus myoclonus in a 23-year-old patient due to STUB1 mutations.

PMID- 24928120
TI  - RoPE: a safety line but tangles remain.

PMID- 24928121
TI  - White matter changes with age utilizing quantitative diffusion MRI.
AB  - OBJECTIVE: To investigate the relationship between older age and mean cerebral
      white matter fiber bundle lengths (FBLs) in specific white matter tracts in the
      brain using quantified diffusion MRI. METHODS: Sixty-three healthy adults older
      than 50 years underwent diffusion tensor imaging. Tractography tracings of
      cerebral white matter fiber bundles were derived from the diffusion tensor
      imaging data. RESULTS: Results revealed significantly shorter FBLs in the
      anterior thalamic radiation for every 1-year increase over the age of 50 years.
      CONCLUSIONS: We investigated the effects of age on FBL in specific white matter
      tracts in the brains of healthy older individuals utilizing quantified diffusion
      MRI. The results revealed a significant inverse relationship between age and FBL.
      Longitudinal studies of FBL across a lifespan are needed to examine the specific
      changes to the integrity of white matter.

PMID- 24928122
TI  - Comment: challenges in defining the clinical spectrum of neurogenetic disorders.

PMID- 24928123
TI  - Recurrent stroke predictors differ in medically treated patients with pathogenic
      vs. other PFOs.
AB  - OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs
      a low likelihood of having an incidental patent foramen ovale (PFO) as defined by
      the Risk of Paradoxical Embolism (RoPE) score. METHODS: Patients in the RoPE
      database with cryptogenic stroke (CS) and PFO were classified as having a
      probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of
      <=6 points, n = 677). We tested 15 clinical, 5 radiologic, and 3
      echocardiographic variables for associations with stroke recurrence using Cox
      survival models with component database as a stratification factor. An
      interaction with RoPE score was checked for the variables that were significant.
      RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years.
      Overall, a higher recurrence risk was associated with an index TIA. For all other
      predictors, effects were significantly different in the 2 RoPE score categories.
      For the low RoPE score group, but not the high RoPE score group, older age and
      antiplatelet (vs warfarin) treatment predicted recurrence. Conversely,
      echocardiographic features (septal hypermobility and a small shunt) and a prior
      (clinical) stroke/TIA were significant predictors in the high but not low RoPE
      score group. CONCLUSION: Predictors of recurrence differ when PFO relatedness is
      classified by the RoPE score, suggesting that patients with CS and PFO form a
      heterogeneous group with different stroke mechanisms. Echocardiographic features
      were only associated with recurrence in the high RoPE score group.

PMID- 24928124
TI  - Symptom onset in autosomal dominant Alzheimer disease: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To identify factors influencing age at symptom onset and disease
      course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based
      criteria for predicting symptom onset in ADAD. METHODS: We have collected
      individual-level data on ages at symptom onset and death from 387 ADAD pedigrees,
      compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer
      Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and
      Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275
      individuals, of whom 1,307 were affected by ADAD with known age at symptom onset.
      We assessed the relative contributions of several factors in influencing age at
      onset, including parental age at onset, age at onset by mutation type and family,
      and APOE genotype and sex. We additionally performed survival analysis using data
      on symptom onset collected from 183 ADAD mutation carriers followed
      longitudinally in the DIAN Study. RESULTS: We report summary statistics on age at
      onset and disease course for 174 ADAD mutations, and discover strong and highly
      significant (p < 10(-16), r2 > 0.38) correlations between individual age at
      symptom onset and predicted values based on parental age at onset and mean ages
      at onset by mutation type and family, which persist after controlling for APOE
      genotype and sex. CONCLUSIONS: Significant proportions of the observed variance
      in age at symptom onset in ADAD can be explained by family history and mutation
      type, providing empirical support for use of these data to estimate onset in
      clinical research.

PMID- 24928126
TI  - Neural control of the heart: recent concepts and clinical correlations.

PMID- 24928125
TI  - Prevalence of fatigue in Parkinson disease and its clinical correlates.
AB  - OBJECTIVE: To assess in a noninterventional setting the prevalence and severity
      of fatigue in patients with Parkinson disease (PD). METHODS: This was a cross
      sectional study conducted in Italian patients with PD. Objectives included the
      evaluation of the current prevalence and severity of fatigue in patients with PD
      measured using the 16-item Parkinson Fatigue Scale (PFS-16), distressing fatigue
      (defined as a PFS-16 mean score >=3.3), and assessment of its clinical
      correlates. RESULTS: A total of 402 patients were enrolled and 394 patients
      completed the PFS-16 questionnaire with a PFS-16 mean (+/-SD) score of 2.87 +/-
      0.99. Of these, 136 patients (33.8%) reported distressing fatigue (PFS-16 mean
      score >=3.3). Patients with distressing fatigue were older (p = 0.044) and had a
      longer duration of PD (p < 0.0001) than those without distressing fatigue. The
      presence of distressing fatigue was associated with higher total Unified
      Parkinson's Disease Rating Scale (UPDRS) scores, poorer quality of life (39-item
      Parkinson's Disease Questionnaire [PDQ-39]), worse social and psychological
      behaviors, a higher severity of depressive symptoms, and a higher prevalence of
      sleep disorders (all p < 0.001). Logistic regression analyses revealed that
      higher total UPDRS scores, female sex, depression, sleep disorders, as well as
      higher UPDRS activities of daily living scores and PDQ-39 mobility scores
      increase the likelihood of distressing fatigue in patients with PD. CONCLUSIONS:
      Approximately one-third of patients with PD have distressing fatigue, which is
      significantly associated with depression and sleep disorders. The fact that the
      presence of fatigue worsens patient quality of life supports the need to better
      diagnose and treat this debilitating symptom.

PMID- 24928127
TI  - PRRT2 and hemiplegic migraine: a complex association.

PMID- 24928128
TI  - High-dose methotrexate with or without rituximab in newly diagnosed primary CNS
      lymphoma.
AB  - OBJECTIVE: To evaluate the efficacy of rituximab (R) when added to high-dose
      methotrexate (HD-MTX) in patients with newly diagnosed immunocompetent primary
      CNS lymphomas (PCNSLs). METHODS: Immunocompetent adults with newly diagnosed
      PCNSL treated at The Johns Hopkins Hospital between 1995 and 2012 were
      investigated. From 1995 to 2008, patients received HD-MTX monotherapy (8 g/m2
      initially every 2 weeks and after complete response [CR] monthly to complete 12
      months of therapy). From 2008 to 2012, patients received the same HD-MTX with
      rituximab (375 mg/m2) with each HD-MTX treatment. CR rates and median overall and
      progression-free survival were analyzed for each patient cohort in this single
      institution, retrospective study. RESULTS: A total of 81 patients were
      identified: 54 received HD-MTX (median age 66 years) while 27 received HD-MTX/R
      (median age 65 years). CR rates were 36% in the HD-MTX cohort and 73% in the HD
      MTX/R cohort (p = 0.0145). Median progression-free survival was 4.5 months in the
      HD-MTX cohort and 26.7 months in the HD-MTX/R cohort (p = 0.003). Median overall
      survival was 16.3 months in the HD-MTX cohort and has not yet been reached in the
      HD-MTX/R cohort (p = 0.01). CONCLUSIONS: The addition of rituximab to HD-MTX
      appears to improve CR rates as well as overall and progression-free survival in
      patients with newly diagnosed PCNSL. Comparisons of long-term survival in the 2
      cohorts await further maturation of the data. CLASSIFICATION OF EVIDENCE: This
      study provides Class III evidence that in immunocompetent patients with PCNSL, HD
      MTX plus rituximab compared with HD-MTX alone improves CR and overall survival
      rates.

PMID- 24928129
TI  - Fabrication of polyelectrolyte multilayered vesicles as inhalable dry powder for
      lung administration of rifampicin.
AB  - A polyelectrolyte complex based on chitosan and carrageenan was used to coat
      rifampicin-loaded vesicles and obtain a dry powder for inhalation by spray
      drying. The polymer complexation on vesicle surface stabilized them and improved
      their adhesion on airways and epithelia cells. Uncoated liposomes were small in
      size, negatively charged and able to incorporate large amounts of rifampicin
      (70%). Coated vesicles were still able to load adequate amounts of drug (~70%)
      but the coating process produced larger particles (1 MUm) that were positively
      charged and with a spherical shape. Aerosol performances, evaluated using the
      next-generation impactor, showed that coated vesicles reached the 50% of fine
      particle fraction and the smallest mass median aerodynamic diameter (2 MUm).
      Rifampicin-loaded uncoated and coated vesicles slowly reduced the A549 cell
      viability over a 48-h incubation time. Moreover, in vitro coated formulations had
      a strong ability to be easily internalized and to greatly prolong the residence
      time of their components in A549 cells compared to uncoated liposomes that were
      rapidly internalized and just as quickly removed.

PMID- 24928130
TI  - Controlled-release triple anti-inflammatory therapy based on novel
      gastroretentive sponges: characterization and magnetic resonance imaging in
      healthy volunteers.
AB  - The current work aimed to develop novel composite sponges of chitosan (CH)
      chondroitin sulfate (CS) as a low-density gastroretentive delivery system for
      lornoxicam (LOR). This triple anti-inflammatory therapy-loaded matrices are
      expected to expand and float upon contact with gastric fluids for prolonged
      times. CH and CS solutions (3%, w/w) were prepared, mixed in different ratios,
      lyophilized, coated with magnesium stearate and compressed. The CH:CS
      interpolymer complex (IPC) was evaluated via FT-IR, DSC, and XRD. The compressed
      sponges were evaluated for appearance, structure, porosity, pore diameter,
      density, wetting-time, floating characteristics, adhesion-retention, and LOR
      release. The gastroretentivity of the best achieved magnetite-loaded sponges was
      monitored in healthy volunteers via MRI. The interaction between CH (protonated
      amino groups) and CS (anionic carboxylate/sulfate groups) proved IPC formation.
      DSC and XRD studies confirmed loss of LOR crystallinity. The sponges possessed
      interconnecting porous-network structures. The porosity, mean pore diameter, and
      bulk density of CH:CS (10:3) IPC sponges were 11.779%, 25.4 nm, and 0.670 g/mL,
      respectively. They showed complete wetting within seconds, gradual size-expansion
      within minutes and prolonged adhesion for hours. Controlled LOR-release profiles
      were tailored over 12h to satisfy individual patient needs. Monitoring of sponges
      via MRI proved their gastroretentivity for at least 5h.

PMID- 24928131
TI  - Microfluidics-assisted engineering of polymeric microcapsules with high
      encapsulation efficiency for protein drug delivery.
AB  - In this study, microfluidic technology was employed to develop protein
      formulations. The microcapsules were produced with a biphasic flow to create
      water-oil-water (W/O/W) double emulsion droplets with ultrathin shells. Optimized
      microcapsule formulations containing 1% (w/w) bovine serum albumin (BSA) in the
      inner phase were prepared with poly(vinyl alcohol), polycaprolactone and
      polyethylene glycol. All the particles were found to be intact and with a
      particle size of 23-47 MUm. Furthermore, the particles were monodisperse, non
      porous and stable up to 4 weeks. The encapsulation efficiency of BSA in the
      microcapsules was 84%. The microcapsules released 30% of their content within 168
      h. This study demonstrates that microfluidics is a powerful technique for
      engineering formulations for therapeutic proteins.

PMID- 24928132
TI  - Validation of the combined ATR-FTIR/tape stripping technique for monitoring the
      distribution of surfactants in the stratum corneum.
AB  - The physical presence of surfactants in the skin is linked to their skin
      irritation potential. Combined ATR-FTIR spectroscopy and tape stripping
      experiments in vitro on porcine ear skin were used to investigate the spatial
      distribution of sodium lauryl ether sulfate (SLES) in the stratum corneum and to
      assess its effects on conformational order of stratum corneum intercellular
      lipids, secondary structure of keratin and skin hydration. It was possible to
      monitor the spatial distribution of SLES in the stratum corneum for the first
      time by subtracting spectra of untreated from treated skin samples and without
      the need of a perdeuterated form. This method of analysis was evaluated by
      addressing potential error sources such as differences in removed amounts of
      corneocytes and intra-individual changes in stratum corneum composition as a
      function of depth. The obtained results indicate a penetration of SLES into deep
      layers of the stratum corneum. Furthermore, SLES treatment led to significantly
      decreased skin hydration levels, whereas the secondary structure of keratin
      remained nearly unaffected. The reliability of this semi-quantitative method of
      analysis was confirmed by receiving a coefficient of determination of 0.9963
      after making a correlation of deep depended absorbances of two different
      characteristic bands with different absorption coefficients. 

PMID- 24928133
TI  - Enhancement in corneal permeability of riboflavin using calcium sequestering
      compounds.
AB  - Ethylenediaminetetraacetic acid, ethylenediamine-N,N'-disuccinic acid and
      ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid are
      polyaminocarboxylic acids that are able to sequester metal ions. Calcium is
      implicated in maintenance of intercellular matrix, zonula occludens (tight
      junctions) and zonula adherens of epithelium and endothelium cells. Corneal
      epithelium is impervious to many aqueous formulations due to it being lipophilic,
      whereby transcellular drug transit is resisted, whilst tight junctions restrict
      access via the paracellular route. Research has shown that integrity of tight
      junctions breaks down through loss of Ca(2+) for endothelial and epithelial
      cells. This study investigates different Ca(2+) sequestering compounds and their
      effect on corneal permeability of riboflavin at physiological pH. Riboflavin is a
      topically administered ocular drug applied during UV-induced corneal cross
      linking for the treatment of keratoconus. 

PMID- 24928134
TI  - Enhancement of the in vitro penetration of quercetin through pig skin by combined
      microneedles and lipid microparticles.
AB  - Silicon microneedle patches were investigated, alone or in combination with lipid
      microparticles (LMs), as a system to improve the in vitro skin penetration of the
      antioxidant flavonoid, quercetin. LMs loaded with quercetin were prepared by melt
      emulsification and sonication. The flavonoid content of LMs was 11.7+/-0.3% and
      their mean diameter and polydispersity index were 8.1 MUm and 0.66, respectively.
      Emulsions containing quercetin, free or microencapsulated, were applied to
      untreated- or microneedle-treated pig skin mounted in Franz diffusion cells. The
      amount of flavonoid penetrated into the stratum corneum and viable epidermis were
      measured by HPLC, after validated tape-stripping and bead mill homogenization
      procedures, respectively. Compared to intact skin, a marked increase in quercetin
      levels permeated into the stratum corneum (from 1.19 +/- 0.12 MUg/cm(2) to 2.23
      +/- 0.54 MUg/cm(2)) and viable epidermis (from 0.10 +/- 0.01 MUg/cm(2) to 0.56 +/
      0.27 MUg/cm(2)) was achieved when skin was treated with the flavonoid-loaded LMs
      in combination with microneedle arrays. Conversely, perforation of the cutaneous
      surface by microneedles did not produce any significant improvement in the skin
      penetration of non-encapsulated quercetin. The enhanced (5.5-fold) intra
      epidermal delivery of quercetin attained by the LM/microneedle strategy described
      here, is particularly relevant since the main quercetin site of action is in the
      epidermis.

PMID- 24928135
TI  - Development of novel benznidazole formulations: physicochemical characterization
      and in vivo evaluation on parasitemia reduction in Chagas disease.
AB  - This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to
      improve its solubility and bioavailability properties. Low-substituted
      hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as
      carriers. BZN solid dispersions containing different ratios of carrier were
      prepared by a freeze-drying process and characterized by SEM, powder X-ray
      diffraction (XRD), differential scanning calorimetry (DSC) and dissolution
      studies. The reduced BNZ crystallinity in the new formulations was confirmed by
      XRD, and supported by DSC. BNZ:L-HPC solid dispersion at a 1:3 ratio (w/w) (SD
      1:3 L-HPC) improved the BNZ dissolution rate (85% at 5 min) in comparison with
      BNZ raw material (23% at 5 min). However, NaDC formulations showed a prolonged
      release (24% at 30 min for SD-1:3 NaDC), due to the formation of a sustained
      release matrix in acidic medium. In vivo studies performed in a murine model of
      Chagas disease showed that the formulation achieving the highest parasitemia
      suppression at a low dose of 25mg/kg/day after five days of treatment was SD-1:3
      L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ),
      suggesting that BNZ:L-HPC systems enhance the bioavailability of the drug.

PMID- 24928136
TI  - The effect of palmitoylation on the conformation and physical stability of a
      model peptide hormone.
AB  - Peptides are ideal drug candidates due to their potency and specificity, but
      suffer from a short half-life and low membrane permeability. Acylation can
      overcome these limitations but the consequences to stability under different
      formulation conditions and stresses are largely unreported. Using synchrotron
      radiation circular dichroism (SRCD), we show that palmitoylation of a 28 amino
      acid peptide hormone (pI 9.82) induced a structural transition from 310-helix to
      alpha-helix, irrespective of buffer type and pH investigated (5.5-8.0) when
      compared to the non acylated analogues. These conformational preferences were
      retained in the presence of non-ionic micelles but not anionic micelles, which
      induced an alpha-helical structure for all peptides. Palmitoylation promoted an
      irreversible peptide denaturation under thermal stress at pH >= 6.5 and increased
      the propensity for loss of helical structure under high photon flux (here used as
      a novel accelerated photostability test). The presence of either ionic or non
      ionic micelles did not recover these conformational changes over the same
      irradiation period. These results demonstrate that acylation can change peptide
      conformation and decrease thermal-/photo-stability, with important consequences
      for drug-development strategies.

PMID- 24928137
TI  - Chitosan-coated liposomes for topical vaginal therapy: assuring localized drug
      effect.
AB  - The choice of drug therapy in pregnant patients suffering from vaginal infections
      is limited by the safety profile of the drug. Assuring the efficient topical
      therapy to avoid systemic absorption is considered the best therapy option.
      Chitosan-coated liposomes have been developed and optimized to assure localized
      therapy of clotrimazole. Chitosan was selected as mucoadhesive polymer both to
      prolong system's retention at the vaginal site and act on biofilms responsible
      for high recurrence of infections. Sonicated liposomes were coated with chitosan
      in three different concentrations, namely 0.1, 0.3 and 0.6% (w/v). Clotrimazole
      containing (22 MUg/mg lipid) chitosan-coated liposomes were in the size range of
      100-200 nm. The in vitro release studies confirmed prolonged release of
      clotrimazole from both non-coated and chitosan-coated liposomes as compared to
      control. The ex vivo penetration experiments performed on the pregnant sheep
      vaginal tissue showed that coated liposomes assured increased clotrimazole tissue
      retention and reduced its penetration as compared to the control. Mucin studies
      revealed that the coating with lower chitosan concentration increased the
      system's mucoadhesive potential, as compared to coating with higher
      concentrations. These results provide a good platform for further in vivo animal
      studies on mucoadhesive liposomes destined to localized vaginal therapy.

PMID- 24928138
TI  - Effect of crystal habits on the surface energy and cohesion of crystalline
      powders.
AB  - The role of surface properties, influenced by particle processing, in particle
      particle interactions (powder cohesion) is investigated in this study. Wetting
      behaviour of mefenamic acid was found to be anisotropic by sessile drop contact
      angle measurements on macroscopic (>1cm) single crystals, with variations in
      contact angle of water from 56.3 degrees  to 92.0 degrees . This is attributed to
      variations in surface chemical functionality at specific facets, and confirmed
      using X-ray photoelectron spectroscopy (XPS). Using a finite dilution inverse gas
      chromatography (FD-IGC) approach, the surface energy heterogeneity of powders was
      determined. The surface energy profile of different mefenamic acid crystal habits
      was directly related to the relative exposure of different crystal facets.
      Cohesion, determined by a uniaxial compression test, was also found to relate to
      surface energy of the powders. By employing a surface modification (silanisation)
      approach, the contribution from crystal shape from surface area and surface
      energy was decoupled. By "normalising" contribution from surface energy and
      surface area, needle shaped crystals were found to be ~2.5* more cohesive
      compared to elongated plates or hexagonal cuboid shapes crystals.

PMID- 24928139
TI  - Use of chemostat cultures mimicking different phases of wine fermentations as a
      tool for quantitative physiological analysis.
AB  - BACKGROUND: Saccharomyces cerevisiae is the most relevant yeast species
      conducting the alcoholic fermentation that takes place during winemaking.
      Although the physiology of this model organism has been extensively studied,
      systematic quantitative physiology studies of this yeast under winemaking
      conditions are still scarce, thus limiting the understanding of fermentative
      metabolism of wine yeast strains and the systematic description, modelling and
      prediction of fermentation processes. In this study, we implemented and validated
      the use of chemostat cultures as a tool to simulate different stages of a
      standard wine fermentation, thereby allowing to implement metabolic flux analyses
      describing the sequence of metabolic states of S. cerevisae along the wine
      fermentation. RESULTS: Chemostat cultures mimicking the different stages of
      standard wine fermentations of S. cerevisiae EC1118 were performed using a
      synthetic must and strict anaerobic conditions. The simulated stages corresponded
      to the onset of the exponential growth phase, late exponential growth phase and
      cells just entering stationary phase, at dilution rates of 0.27, 0.04, 0.007 h-1,
      respectively. Notably, measured substrate uptake and product formation rates at
      each steady state condition were generally within the range of corresponding
      conversion rates estimated during the different batch fermentation
      stages.Moreover, chemostat data were further used for metabolic flux analysis,
      where biomass composition data for each condition was considered in the
      stoichiometric model. Metabolic flux distributions were coherent with previous
      analyses based on batch cultivations data and the pseudo-steady state assumption.
      CONCLUSIONS: Steady state conditions obtained in chemostat cultures reflect the
      environmental conditions and physiological states of S. cerevisiae corresponding
      to the different growth stages of a typical batch wine fermentation, thereby
      showing the potential of this experimental approach to systematically study the
      effect of environmental relevant factors such as temperature, sugar
      concentration, C/N ratio or (micro) oxygenation on the fermentative metabolism of
      wine yeast strains.

PMID- 24928140
TI  - Access to health services for undocumented immigrants in Apulia.
AB  - This paper, part of a larger epidemiological study carried out between 2004 and
      2010, analyzed immigrants frequenting the largest Apulian regional hospital (Bari
      Policlinico). Our aim was to evaluate the perception on the part of undocumented
      immigrants of their rights of access to the National Health Care services and
      whether this privilege is actually utilized. An anonymous multi-language
      questionnaire was distributed to all patients with STP (code number for temporary
      presence of foreigners) at the immigrant outpatient Infectious Diseases Clinic of
      Bari from June 2009 to June 2010. Questions were related to nationality, date of
      arrival in Italy, use of health facilities in the 2 years prior to the
      compilation of the questionnaire, and their understanding of STP. The patients
      were also screened for infectious diseases (HIV-Ab, HBsAg, HCV-Ab, VDRL, TPHA and
      Mantoux). A total of 256/272 patients completed the questionnaire; the meaning of
      STP was unknown to 156/256 (60.9%) patients, only 54/256 (21%) knew the exact
      meaning of STP and only 42/54 (76.6%) of the latter knew how long STP was valid.
      Moreover, 128/256 (50.7%) were aware that doctors from the emergency unit were
      not allowed to notify police regarding presence of illegal immigrants. Regarding
      clinical data 3% were HIV+ (8/256), 5% (13 patients) positive for TPHA, 5% for
      HBsAg, 2% were HCV (five patients). A >10 mm diameter infiltrate of Mantoux test
      was noted for 44% of patients. A lower prevalence than expected for infections
      such as HIV, HBV or HCV was noted for immigrants compared to data from their
      countries of origin. At present, large-scale political solutions to the
      challenges of facilitating access to health facilities for undocumented
      immigrants are lacking in Italy. The development of communication systems is
      fundamental to improving access to health services and to creating links between
      immigrants and the healthcare system.

PMID- 24928141
TI  - Influences of smoking and caffeine consumption on trigeminal pain processing.
AB  - BACKGROUND: Many human and animal studies have shown the influence of nicotine
      and caffeine on pain perception and processing. This study aims to investigate
      whether smoking or caffeine consumption influences trigeminal pain processing.
      METHODS: Sixty healthy subjects were investigated using simultaneous recordings
      of the nociceptive blink reflex (nBR) and pain related evoked potentials (PREP)
      following nociceptive electrical stimulation on both sides of the forehead (V1).
      Thirty subjects were investigated before and after smoking a cigarette, as well
      as before and after taking a tablet of 400 mg caffeine. RESULTS: After smoking
      PREP showed decreased N2 and P2 latencies indicating central facilitation at
      supraspinal (thalamic or cortical) level. PREP amplitudes were not changed. NBR
      showed a decreased area under the curve (AUC) indicating central inhibition at
      brainstem level. After caffeine intake no significant changes were observed
      comparing nBR and PREP results before consumption. CONCLUSIONS: Smoking
      influences trigeminal pain processing on supraspinal and brainstem level. In the
      investigated setting, caffeine consumption does not significantly alter
      trigeminal pain processing. This observation might help in the further
      understanding of the pathophysiology of pain disorders that are associated with
      excessive smoking habits such as cluster headache. Previous smoking has to be
      taken into account when performing electrophysiological studies to avoid bias of
      study results.

PMID- 24928142
TI  - Peripheral administration of morphine attenuates postincisional pain by
      regulating macrophage polarization through COX-2-dependent pathway.
AB  - BACKGROUND: Macrophage infiltration to inflammatory sites promotes wound repair
      and may be involved in pain hypersensitivity after surgical incision. We recently
      reported that the development of hyperalgesia during chronic inflammation is
      regulated by macrophage polarity, often referred to as proinflammatory (M1) or
      anti-inflammatory (M2) macrophages. Although opioids such as morphine are known
      to alter the inflammatory milieu of incisional wounds through interactions with
      immunocytes, the macrophage-mediated effects of morphine on the development of
      postincisional pain have not been well investigated. In this study, we examined
      how morphine alters pain hypersensitivity through phenotypic shifts in local
      macrophages during the course of incision-induced inflammation. RESULTS: Local
      administration of morphine in the early phase, but not in the late phase
      alleviated mechanical hyperalgesia, and this effect was reversed by clodronate
      induced peripheral depletion of local macrophages. At the morphine-injected
      incisional sites, the number of pro-inflammatory F4/80+iNOS+M1 macrophages was
      decreased during the course of pain development whereas increased infiltration of
      wound healing F4/80+CD206+M2 macrophages was observed during the early phase.
      Morphine increased the gene expression of endogenous opioid, proenkephalin, and
      decreased the pronociceptive cytokine, interleukin-1beta. Heme oxygenase (HO)-1
      promotes the differentiation of macrophages to the M2 phenotype. An inhibitor of
      HO-1, tin protoporphyrin reversed morphine-induced analgesic effects and the
      changes in macrophage phenotype. However, local expression levels of HO-1 were
      not altered by morphine. Conversely, cyclooxygenase (COX)-2, primarily produced
      from peripheral macrophages in acute inflammation states, was up-regulated in the
      early phase at morphine-injected sites. In addition, the analgesic effects and a
      phenotype switching of infiltrated macrophages by morphine was reversed by local
      administration of a COX inhibitor, indomethacin. CONCLUSIONS: Local
      administration of morphine alleviated the development of postincisional pain,
      possibly by altering macrophage polarity at the incisional sites. A morphine
      induced shift in macrophage phenotype may be mediated by a COX-2-dependent
      mechanism. Therefore, MU-opioid receptor signaling in macrophages may be a
      potential therapeutic target during the early phase of postincisional pain
      development.

PMID- 24928143
TI  - ZebRA: An overview of retinoic acid signaling during zebrafish development.
AB  - Retinoic acid (RA), the main active vitamin A derivative, is crucial for embryo
      development, regulating cellular processes, embryo patterning and organogenesis.
      Many studies performed in mammalian or avian models have successfully undertaken
      the investigation of the role played by RA during embryogenesis. Since the early
      1980s, the zebrafish (Danio rerio) has emerged as a powerful developmental model
      to study the in vivo role of RA during embryogenesis. Unlike mammalian models,
      zebrafish embryogenesis is external, not only allowing the observation of the
      translucent embryo from the earliest steps but also providing an easily
      accessible system for pharmacological treatment or genetic approaches. Therefore,
      zebrafish research largely participates in deciphering the role of RA during
      development. This review aims at illustrating different concepts of RA signaling
      based on the research performed on zebrafish. Indeed, RA action relies on a
      multitude of cross-talk with other signaling pathways and requires a coordinated,
      dynamic and fine-regulation of its level and activity in both temporal and
      spatial dimensions. This review also highlights major advances that have been
      discovered using zebrafish such as the observation of the RA gradient in vivo for
      the first time, the effects of RA signaling in brain patterning, its role in
      establishing left-right asymmetry and its effects on the development of a variety
      of organs and tissues including the heart, blood, bone and fat. This review
      demonstrates that the zebrafish is a convenient and powerful model to study
      retinoic acid signaling during vertebrate embryogenesis. This article is part of
      a Special Issue entitled: Nuclear receptors in animal development. 

PMID- 24928145
TI  - Novel recessive myotilin mutation causes severe myofibrillar myopathy.
AB  - We identified the first homozygous and hence recessive mutation in the myotilin
      gene (MYOT) in a family affected by a severe myofibrillar myopathy (MFM). MFM is
      a rare, progressive and devastating disease of human skeletal muscle with
      distinct histopathological pattern of protein aggregates and myofibrillar
      degeneration. So far, only heterozygous missense mutations in MYOT have been
      associated with autosomal dominant myofibrillar myopathy, limb-girdle muscular
      dystrophy type 1A and distal myopathy. Myotilin itself is highly expressed in
      skeletal and cardiac muscle and is localized at the Z-disc and therefore
      interacts in sarcomere assembly. We performed whole-exome sequencing in a German
      family clinically diagnosed with MFM and identified a homozygous mutation in exon
      2, c.16C > G (p.Arg6Gly). Using laser microdissection followed by quantitative
      mass spectrometry, we identified the myotilin protein as one component showing
      the highest increased abundance in the aggregates in the index patient. We
      suggest that the combined approach has a high potential as a new tool for the
      confirmation of unclassified variants which are found in whole-exome sequencing
      approaches. 

PMID- 24928144
TI  - 'Neuroinflammation' differs categorically from inflammation: transcriptomes of
      Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases
      compared.
AB  - 'Neuroinflammation' has become a widely applied term in the basic and clinical
      neurosciences but there is no generally accepted neuropathological tissue
      correlate. Inflammation, which is characterized by the presence of perivascular
      infiltrates of cells of the adaptive immune system, is indeed seen in the central
      nervous system (CNS) under certain conditions. Authors who refer to microglial
      activation as neuroinflammation confuse this issue because autoimmune
      neuroinflammation serves as a synonym for multiple sclerosis, the prototypical
      inflammatory disease of the CNS. We have asked the question whether a data
      driven, unbiased in silico approach may help to clarify the nomenclatorial
      confusion. Specifically, we have examined whether unsupervised analysis of
      microarray data obtained from human cerebral cortex of Alzheimer's, Parkinson's
      and schizophrenia patients would reveal a degree of relatedness between these
      diseases and recognized inflammatory conditions including multiple sclerosis. Our
      results using two different data analysis methods provide strong evidence against
      this hypothesis demonstrating that very different sets of genes are involved.
      Consequently, the designations inflammation and neuroinflammation are not
      interchangeable. They represent different categories not only at the
      histophenotypic but also at the transcriptomic level. Therefore, non-autoimmune
      neuroinflammation remains a term in need of definition. 

PMID- 24928146
TI  - The Functional Reach Test: strategies, performance and the influence of age.
AB  - BACKGROUND: The Functional Reach Test (FRT) is a clinical assessment of the risk
      of falls in elderly or disabled subjects. However, the FRT is complex (involving
      the leg, hip and trunk joints) and previous studies have shown that several
      different strategies can be used to complete the test. OBJECTIVES: To describe
      the strategies used by healthy, adult subjects when performing the FRT and to
      assess the influence of age on choice of the strategy. METHOD: This was a pilot
      study in which 29 non-fallers (18 under-50s and 11 over-75s) were asked to
      perform the FRT on a force platform in a motion analysis laboratory. A total of
      18 reflective markers were placed on the body. The main outcome measures were the
      FRT score, the centre of pressure (CoP) excursion, and kinetic and kinematic test
      data. The two age groups were compared using a non-parametric, two-sample Mann
      Whitney U test. A cluster analysis of the entire population grouped subjects
      together according to their functional similarities. RESULTS: The older subjects
      displayed a smaller CoP anteroposterior displacement (P<0.01), greater backwards
      displacement of the pelvis (P<0.05) and less trunk rotation during the FRT
      (P=0.024) than the younger subjects. The cluster analysis split the population
      into two groups, which differed in terms of age, FRT score, pelvis translation,
      and CoP displacement. CONCLUSION: Our results suggest that at the moment of trunk
      flexion, elderly subjects use pelvic translation in order to limit forward
      displacement of the CoP and prevent forward imbalance.

PMID- 24928148
TI  - Innate and intrinsic antiviral immunity in skin.
AB  - As the body's most exposed interface with the environment, the skin is constantly
      challenged by potentially pathogenic microbes, including viruses. To sense the
      invading viruses, various types of cells resident in the skin express many
      different pattern-recognition receptors (PRRs) such as C-type lectin receptors
      (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain
      (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like
      receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen
      associated molecular patterns (PAMPs) of the viruses. The detection of viral
      PAMPs initiates two major innate immune signaling cascades: the first involves
      the activation of the downstream transcription factors, such as interferon
      regulatory factors (IRFs), nuclear factor kappa B (NF-kappaB) and activator
      protein 1 (AP-1), which cooperate to induce the transcription of type I
      interferons and pro-inflammatory cytokines. The second signaling pathway involves
      the caspase-1-mediated processing of IL-1beta and IL-18 through the formation of
      an inflammasome complex. Cutaneous innate immunity including the production of
      the innate cytokines constitutes the first line of host defence that limits the
      virus dissemination from the skin, and also plays an important role in the
      activation of adaptive immune response, which represents the second line of
      defence. More recently, the third immunity "intrinsic immunity" has emerged, that
      provides an immediate and direct antiviral defense mediated by host intrinsic
      restriction factors. This review focuses on the recent advances regarding the
      antiviral immune systems, highlighting the innate and intrinsic immunity against
      the viral infections in the skin, and describes how viral components are
      recognized by cutaneous immune systems. 

PMID- 24928147
TI  - Reprogramming approaches in cardiovascular regeneration.
AB  - OPINION STATEMENT: Reconstitution of cardiac muscle as well as blood vessels to
      provide sufficient oxygenation and nutrients to the myocardium is an important
      component of any therapeutic approach for cardiac repair after injury. Recent
      reports of reprogramming somatic cells directly to cells of another lineage
      raised the possibility of using cell reprogramming for cardiac regenerative
      therapy. Here, we provide an overview of the current reprogramming strategies to
      generate cardiomyocytes (CMs), endothelial cells (ECs) and smooth muscle cells
      (SMCs), and the implications of these methods for cardiac regeneration. We also
      discuss the challenges and limitations that need to be addressed for the
      development of future therapies.

PMID- 24928149
TI  - Effect of pressure on the chromatographic separation of enantiomers under
      reversed-phase conditions.
AB  - Commercially available ultra high pressure liquid chromatography (UHPLC)
      equipment offers the ability to explore the influence of backpressure on
      chromatographic separations. However, the influence of pressure on the
      chromatographic separation of enantiomers on chiral stationary phases remains
      largely unexplored. In this investigation we surveyed the effects of pressure on
      the separation of enantiomers using several reversed-phase chiral stationary
      phases. The experiments were conducted at constant flow rate and column
      temperature, using isocratic conditions. The only variable parameter was
      pressure, which was adjusted using a post-column backpressure regulator. For the
      separation of enantiomers on chiral stationary phases, an increase in pressure
      from approximately 2,000 psi (138 bar) to approximately 8,000 psi (552 bar) at
      constant flow rate and temperature led to an increase of retention factors for
      some analytes and a decrease for others. Achiral separations on a C-18 stationary
      phase always led only to an increase of retention factor. Interestingly, changes
      in pressure led to small changes in enantioselectivity during reversed-phase
      chiral separation of enantiomers, suggesting that such studies may be of value
      for better understanding the mechanisms underlying chromatographic
      enantioseparation.

PMID- 24928150
TI  - From cultural traditions to cumulative culture: parameterizing the differences
      between human and nonhuman culture.
AB  - Diverse species exhibit cultural traditions, i.e. population-specific profiles of
      socially learned traits, from songbird dialects to primate tool-use behaviours.
      However, only humans appear to possess cumulative culture, in which cultural
      traits increase in complexity over successive generations. Theoretically, it is
      currently unclear what factors give rise to these phenomena, and consequently why
      cultural traditions are found in several species but cumulative culture in only
      one. Here, we address this by constructing and analysing cultural evolutionary
      models of both phenomena that replicate empirically attestable levels of cultural
      variation and complexity in chimpanzees and humans. In our model of cultural
      traditions (Model 1), we find that realistic cultural variation between
      populations can be maintained even when individuals in different populations
      invent the same traits and migration between populations is frequent, and under a
      range of levels of social learning accuracy. This lends support to claims that
      putative cultural traditions are indeed cultural (rather than genetic) in origin,
      and suggests that cultural traditions should be widespread in species capable of
      social learning. Our model of cumulative culture (Model 2) indicates that both
      the accuracy of social learning and the number of cultural demonstrators interact
      to determine the complexity of a trait that can be maintained in a population.
      Combining these models (Model 3) creates two qualitatively distinct regimes in
      which there are either a few, simple traits, or many, complex traits. We suggest
      that these regimes correspond to nonhuman and human cultures, respectively. The
      rarity of cumulative culture in nature may result from this interaction between
      social learning accuracy and number of demonstrators. 

PMID- 24928151
TI  - Memory effects in biochemical networks as the natural counterpart of extrinsic
      noise.
AB  - We show that in the generic situation where a biological network, e.g. a protein
      interaction network, is in fact a subnetwork embedded in a larger "bulk" network,
      the presence of the bulk causes not just extrinsic noise but also memory effects.
      This means that the dynamics of the subnetwork will depend not only on its
      present state, but also its past. We use projection techniques to get explicit
      expressions for the memory functions that encode such memory effects, for generic
      protein interaction networks involving binary and unary reactions such as complex
      formation and phosphorylation. Remarkably, in the limit of low intrinsic copy
      number noise such expressions can be obtained even for nonlinear dependences on
      the past. We illustrate the method with examples from a protein interaction
      network around epidermal growth factor receptor (EGFR), which is relevant to
      cancer signalling. These examples demonstrate that inclusion of memory terms is
      not only important conceptually but also leads to substantially higher
      quantitative accuracy in the predicted subnetwork dynamics. 

PMID- 24928152
TI  - Transmission of intra-cellular genetic information: a system proposal.
AB  - One of the great challenges of the scientific community on theories of genetic
      information, genetic communication and genetic coding is to determine a
      mathematical structure related to DNA sequences. In this paper we propose a model
      of an intra-cellular transmission system of genetic information similar to a
      model of a power and bandwidth efficient digital communication system in order to
      identify a mathematical structure in DNA sequences where such sequences are
      biologically relevant. The model of a transmission system of genetic information
      is concerned with the identification, reproduction and mathematical
      classification of the nucleotide sequence of single stranded DNA by the genetic
      encoder. Hence, a genetic encoder is devised where labelings and cyclic codes are
      established. The establishment of the algebraic structure of the corresponding
      codes alphabets, mappings, labelings, primitive polynomials (p(x)) and code
      generator polynomials (g(x)) are quite important in characterizing error
      correcting codes subclasses of G-linear codes. These latter codes are useful for
      the identification, reproduction and mathematical classification of DNA
      sequences. The characterization of this model may contribute to the development
      of a methodology that can be applied in mutational analysis and polymorphisms,
      production of new drugs and genetic improvement, among other things, resulting in
      the reduction of time and laboratory costs. 

PMID- 24928153
TI  - Modeling forest ecosystem responses to elevated carbon dioxide and ozone using
      artificial neural networks.
AB  - Rising atmospheric levels of carbon dioxide and ozone will impact productivity
      and carbon sequestration in forest ecosystems. The scale of this process and the
      potential economic consequences provide an incentive for the development of
      models to predict the types and rates of ecosystem responses and feedbacks that
      result from and influence of climate change. In this paper, we use phenotypic and
      molecular data derived from the Aspen Free Air CO2 Enrichment site (Aspen-FACE)
      to evaluate modeling approaches for ecosystem responses to changing conditions.
      At FACE, it was observed that different aspen clones exhibit clone-specific
      responses to elevated atmospheric levels of carbon dioxide and ozone. To identify
      the molecular basis for these observations, we used artificial neural networks
      (ANN) to examine above and below-ground community phenotype responses to elevated
      carbon dioxide, elevated ozone and gene expression profiles. The aspen community
      models generated using this approach identified specific genes and subnetworks of
      genes associated with variable sensitivities for aspen clones. The ANN model also
      predicts specific co-regulated gene clusters associated with differential
      sensitivity to elevated carbon dioxide and ozone in aspen species. The results
      suggest ANN is an effective approach to predict relevant gene expression changes
      resulting from environmental perturbation and provides useful information for the
      rational design of future biological experiments. 

PMID- 24928154
TI  - Photoacoustic resonance spectroscopy for biological tissue characterization.
AB  - By "listening to photons," photoacoustics allows the probing of chromosomes in
      depth beyond the optical diffusion limit. Here we report the photoacoustic
      resonance effect induced by multiburst modulated laser illumination, which is
      theoretically modeled as a damped mass-string oscillator and a resistor-inductor
      capacitor (RLC) circuit. Through sweeping the frequency of multiburst modulated
      laser, the photoacoustic resonance effect is observed experimentally on phantoms
      and porcine tissues. Experimental results demonstrate different spectra for each
      phantom and tissue sample to show significant potential for spectroscopic
      analysis, fusing optical absorption and mechanical vibration properties. Unique
      RLC circuit parameters are extracted to quantitatively characterize phantom and
      biological tissues.

PMID- 24928155
TI  - Development of a prediction method for skin sensitization using novel cysteine
      and lysine derivatives.
AB  - INTRODUCTION: The Direct Peptide Reactivity Assay (DPRA) was developed as an
      alternative simple and versatile method for predicting skin sensitization. Here,
      we describe a novel Amino acid Derivative Reactivity Assay (ADRA) involving 2
      amino acid derivatives: N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC) and alpha-N-(2
      (1-naphthyl)acetyl)-l-lysine (NAL), in which each amino-terminal residue is
      introduced into a naphthalene ring. ADRA measurements were conducted at 281nm,
      which improved baseline stability, and were less influenced by other substances
      in the reaction solutions than DPRA measurements that are conducted at 220nm.
      METHODS: Chemically synthesized NAC and NAL were dissolved in phosphate buffers
      of pH9.5 and 12.0, respectively. Each solution, test chemical solution, and
      phosphate buffer, were mixed in 96-well microplates and incubated in the dark for
      24h at 25 degrees C. Following incubation, samples were diluted 10 times with a
      mixed solution of 25% acetonitrile/0.5% trifluoroacetic acid (TFA) in water, and
      NAC and NAL levels were quantified in each sample and control using a high
      performance liquid chromatography (HPLC) system. The reactivity of NAC/NAL was
      calculated as the percent depletion based on the decrease in the non-reacted
      NAC/NAL concentration in the samples relative to the average concentration in the
      control; the average NAC/NAL reduction score was calculated. A 2-class
      classification model was developed using ADMEWORKS/ModelBuilder, and an optimal
      average score that could discriminate between sensitizers and non-sensitizers was
      determined. RESULTS: A total of 82 test chemicals were applied to ADRA for
      comparison against DPRA. The prediction accuracy of ADRA was 88%, which was
      similar to that of DPRA. DISCUSSION: ADRA was used to quantify NAC/NAL at 281nm,
      which showed high accuracy for the prediction of skin sensitization, similar to
      that of DPRA. Therefore, ADRA could be used to expand the range of chemicals
      tested in skin sensitization analyses.

PMID- 24928156
TI  - Radiology education: keeping pace with changing times, new technology, and
      increased challenges.

PMID- 24928157
TI  - Radiology resident mammography training: interpretation difficulty and error
      making patterns.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to better understand the
      concept of mammography difficulty and how it affects radiology resident
      performance. MATERIALS AND METHODS: Seven radiology residents and three expert
      breast imagers reviewed 100 mammograms, consisting of bilateral medial lateral
      oblique and craniocaudal views, using a research workstation. The cases consisted
      of normal, benign, and malignant findings. Participants identified abnormalities
      and scored the difficulty and malignant potential for each case. Resident
      performance (sensitivity, specificity, and area under the receiver operating
      characteristic curve [AUC]) was calculated for self- and expert-assessed high and
      low difficulties. RESULTS: For cases classified by self-assessed difficulty, the
      resident AUCs were 0.667 for high difficulty and 0.771 for low difficulty cases
      (P = .010). Resident sensitivities were 0.707 for high and 0.614 for low
      difficulty cases (P = .113). Resident specificities were 0.583 for high and 0.905
      for low difficulty cases (P < .001). For cases classified by expert-assessed
      difficulty, the resident AUCs were 0.583 for high and 0.783 for low difficulty
      cases (P = .001). Resident sensitivities were 0.558 for high and 0.796 for low
      difficulty cases (P < .001). Resident specificities were 0.714 for high and 0.740
      for low difficulty cases (P = .807). CONCLUSIONS: Increased self- and expert
      assessed difficulty is associated with a decrease in resident performance in
      mammography. However, while this lower performance is due to a decrease in
      specificity for self-assessed difficulty, it is due to a decrease in sensitivity
      for expert-assessed difficulty. These trends suggest that educators should
      provide a mix of self- and expert-assessed difficult cases in educational
      materials to maximize the effect of training on resident performance and
      confidence.

PMID- 24928159
TI  - A tissue phantom model for training residents in ultrasound-guided liver biopsy.
AB  - RATIONALE AND OBJECTIVES: The apprenticeship model for training of percutaneous
      liver biopsy has limitations, and costs of commercially available simulation
      models can be prohibitive. We created an inexpensive tissue phantom for liver
      biopsy simulation and evaluated the utility of this model for training radiology
      residents. MATERIALS AND METHODS: A bovine-porcine tissue phantom was devised as
      a simulation model and consisted of bovine liver with a porcine rib layer and
      inserted pimento olives simulating target lesions. Training sessions (a 20-minute
      didactic lecture and a 90-minute practice session) were offered to all residents
      in a diagnostic radiology residency. Effect of training was assessed by
      questionnaire before and after training. Level of knowledge of topics covered in
      the didactic session, confidence in technical skills, and anxiety level were
      evaluated on a five-point scale (1, poor to 5, excellent). RESULTS: Thirty-five
      of 38 residents received training on the models (~$40). Mean reported value score
      for training was 4.88/5. Improvement was greatest for knowledge of technique (2.3
      4.1/5, P < .001) and knowledge of postprocedure care (2.2-4.1/5, P < .001).
      Technical confidence increased (2.4-3.8/5, P < .001) and anxiety related to
      performing liver biopsy improved (2.7-3.7/5, P < .001). Residents with no prior
      experience in liver biopsy (n = 21) had significantly greater increases in all
      categories than residents with prior experience (n = 14), except for knowledge
      about obtaining informed consent and anxiety levels. CONCLUSIONS: Utilization of
      an inexpensively created bovine/porcine liver biopsy simulation model was well
      perceived by radiology residents and can be used as an educational tool during
      residency.

PMID- 24928158
TI  - Teaching point of care ultrasound skills in medical school: keeping radiology in
      the driver's seat.
AB  - RATIONALE AND OBJECTIVES: Ultrasound is used increasingly in medical practice as
      a tool for focused bedside diagnosis and technical assistance during procedures.
      Widespread availability of small portable units has put this technology into the
      hands of many physicians and medical students who lack dedicated training,
      leaving the education and introduction of this key modality increasingly to
      physicians from other specialties. We developed a radiology-led program to teach
      ultrasound skills to preclinical medical students. MATERIALS AND METHODS: To
      develop this new ultrasound program we 1) established a program leader, 2)
      developed teaching materials, 3) created a hands-on interactive program, and 4)
      recruited the necessary instructors. The program was piloted with the first-year
      medical student class of 154 students. The introductory session was assessed by
      pre- and post-activity Likert scale-based surveys. RESULTS: Of 154 (68.8%)
      students, 106 completed a voluntary online survey before starting the program and
      145 students (94.2%) completed a voluntary survey after the session. Students
      found the program educationally valuable (4.64 of 5) and reported that it
      improved their understanding of ultrasound imaging (4.7 of 5). Students' reported
      confidence in identifying abdominal organs, intra-abdominal fluid, and Morison
      pouch that was significantly higher on the postactivity survey compared to the
      presurvey (P < .001 for all). CONCLUSIONS: We piloted a radiology-led program to
      teach ultrasound skills to preclinical medical students. Students found the
      experience enjoyable and educationally valuable.

PMID- 24928160
TI  - Residents' ability to interpret radiology images: development and improvement of
      an assessment tool.
AB  - RATIONALE AND OBJECTIVES: Despite increasing radiology coverage, nonradiology
      residents continue to preliminarily interpret basic radiologic studies
      independently, yet their ability to do so accurately is not routinely assessed.
      MATERIALS AND METHODS: An online test of basic radiologic image interpretation
      was developed through an iterative process. Educational objectives were
      established, then questions and images were gathered to create an assessment. The
      test was administered online to first-year interns (postgraduate year [PGY] 1)
      from 14 different specialties, as well as a sample of third- and fourth-year
      radiology residents (PGY3/R2 and PGY4/R3). RESULTS: Over a 2-year period, 368
      residents were assessed, including PGY1 (n = 349), PGY3/R2 (n = 14), and PGY4/R3
      (n = 5) residents. Overall, the test discriminated effectively between interns
      (average score = 66%) and advanced residents (R2 = 86%, R3 = 89%; P < .05). Item
      analysis indicated discrimination indices ranging from -0.72 to 48.3 (mean =
      3.12, median 0.58) for individual questions, including four questions with
      negative discrimination indices. After removal of the negatively indexed
      questions, the overall predictive value of the instrument persisted and
      discrimination indices increased for all but one of the remaining questions
      (range 0.027-70.8, mean 5.76, median 0.94). CONCLUSIONS: Validation of an initial
      iteration of an assessment of basic image-interpretation skills led to revisions
      that improved the test. The results offer a specific test of radiologic reading
      skills with validation evidence for residents. More generally, results
      demonstrate a principled approach to test development.

PMID- 24928161
TI  - The key image and case log application: new radiology software for teaching file
      creation and case logging that incorporates elements of a social network.
AB  - RATIONALE AND OBJECTIVES: To create novel radiology key image software that is
      easy to use for novice users, incorporates elements adapted from social
      networking Web sites, facilitates resident and fellow education, and can serve as
      the engine for departmental sharing of interesting cases and follow-up studies.
      MATERIALS AND METHODS: Using open-source programming languages and software,
      radiology key image software (the key image and case log application, KICLA) was
      developed. This system uses a lightweight interface with the institutional
      picture archiving and communications systems and enables the storage of key
      images, image series, and cine clips. It was designed to operate with minimal
      disruption to the radiologists' daily workflow. Many features of the user
      interface have been inspired by social networking Web sites, including image
      organization into private or public folders, flexible sharing with other users,
      and integration of departmental teaching files into the system. We also review
      the performance, usage, and acceptance of this novel system. RESULTS: KICLA was
      implemented at our institution and achieved widespread popularity among
      radiologists. A large number of key images have been transmitted to the system
      since it became available. After this early experience period, the most commonly
      encountered radiologic modalities are represented. A survey distributed to users
      revealed that most of the respondents found the system easy to use (89%) and fast
      at allowing them to record interesting cases (100%). Hundred percent of
      respondents also stated that they would recommend a system such as KICLA to their
      colleagues. CONCLUSIONS: The system described herein represents a significant
      upgrade to the Digital Imaging and Communications in Medicine teaching file
      paradigm with efforts made to maximize its ease of use and inclusion of
      characteristics inspired by social networking Web sites that allow the system
      additional functionality such as individual case logging.

PMID- 24928162
TI  - Radiology resident recruitment: A study of the impact of web-based information
      and interview day activities.
AB  - RATIONALE AND OBJECTIVES: Residency recruitment is a critical and expensive
      process. A program's Web site may improve recruitment, but little is known about
      how applicants use program sites or what constitutes optimal content. The
      importance of an interview day and interactions with a program's residents has
      been described, but candidate preferences for various activities and schedules
      have not been widely reported. We investigated contemporary use and perceived
      utility of information provided on radiology program Web sites, as well as
      preferences for the interview day experience. MATERIALS AND METHODS: Using an
      anonymous cross-sectional survey, we studied 111 candidates who were interviewed
      between November 1, 2012 and January 19, 2013 for a diagnostic radiology
      residency position at our institution. Participation in this institutional review
      board-approved study was entirely voluntary, and no identifying information was
      collected. Responses were sealed and not analyzed until after the match. RESULTS:
      A total of 70 candidates returned a completed survey (63% response rate). Optimal
      content considered necessary for a "complete" Web site was identified. The most
      important factor in deciding where to apply was geographical connection to a
      program. "AuntMinnie" was the most popular source of program information on
      social media. Candidates overwhelmingly preferred one-on-one faculty interviews
      but had no preference between a Saturday and weekday schedule. The ideal
      interview experience should include a "meet and greet" with residents off campus
      and a personal interview with the program director. The overall "feel" or
      "personality" of the program was critical to a candidate's rank order decision.
      CONCLUSIONS: Our findings offer insight into what factors make programs appealing
      to radiology applicants. This information will be useful to medical educators
      engaged in career counseling and recruitment.

PMID- 24928163
TI  - Residents' performance in the interpretation of on-call "triple-rule-out" CT
      studies in patients with acute chest pain.
AB  - RATIONALE AND OBJECTIVES: To evaluate the performance of radiology residents in
      the interpretation of on-call, emergency "triple-rule-out" (TRO) computed
      tomographic (CT) studies in patients with acute chest pain. MATERIALS AND
      METHODS: The study was institutional review board-approved and Health Insurance
      Portability and Accountability Act compliant. Data from 617 on-call TRO studies
      were analyzed. Dedicated software enables subspecialty attendings to grade
      discrepancies in interpretation between preliminary trainee reports and their
      final interpretation as "unlikely to be significant" (minor discrepancies) or
      "likely to be significant" for patient management (major discrepancies). The
      frequency of minor, major and all discrepancies in resident's TRO interpretations
      was compared to 609 emergent non-electrocardiography (ECG)-synchronized chest CT
      studies using Pearson chi(2) test. RESULTS: Minor discrepancies occurred more
      often in the TRO group (9.1% vs. 3.9%, P < .001), but there was no difference in
      the frequency of major discrepancies (2.1% vs. 2.8%, P = .55). Minor
      discrepancies in the TRO group most commonly resulted from missed extrathoracic
      findings with missed liver lesions being the most frequent. Major discrepancies
      mostly encompassed cardiac and extracardiac vascular findings but did not result
      in unnecessary interventions, significant immediate changes in management, or
      adverse patient outcomes. CONCLUSIONS: On-call resident interpretation of TRO CT
      studies in patients with acute chest pain is congruent with final subspecialty
      attending interpretation in the overwhelming majority of cases. The rate of
      discrepancies likely to affect patient management in this domain is not different
      from emergent non-ECG-synchronized chest CT.

PMID- 24928164
TI  - Radiology 101: Water.

PMID- 24928165
TI  - Engineered aggregation inhibitor fusion for production of highly amyloidogenic
      human islet amyloid polypeptide.
AB  - Human islet amyloid polypeptide (IAPP) is the major component of pancreatic
      amyloid deposits in type 2 diabetes. The structural conversion of IAPP from a
      monomeric state into amyloid assemblies is the subject of intense research.
      Recombinant production of IAPP is, however, difficult due to its extreme
      aggregation propensity. Here we describe a novel strategy for expression of IAPP
      in Escherichia coli, based on an engineered protein tag, which sequesters IAPP
      monomers and prevents IAPP aggregation. The IAPP-binding protein HI18 was
      selected by phage display from a beta-wrapin library. Fusion of HI18 to IAPP
      enabled the soluble expression of the construct. IAPP was cleaved from the fusion
      construct and purified to homogeneity with a yield of 3mg of isotopically labeled
      peptide per liter of culture. In the monomeric state, IAPP was largely disordered
      as evidenced by far-UV CD and liquid-state NMR spectroscopy but competent to form
      amyloid fibrils according to atomic force microscopy. These results demonstrate
      the ability of the engineered beta-wrapin HI18 for shielding the hydrophobic
      sequence of IAPP during expression and purification. Fusion of aggregation
      inhibiting beta-wrapins is a suitable approach for the recombinant production of
      aggregation-prone proteins. 

PMID- 24928166
TI  - Animal welfare and society concerns finding the missing link.
AB  - Young adults in developed countries are distanced from agriculture and the meat
      industry needs to do a better job of communicating with them. A major welfare
      concern is slaughter without stunning. Other concerns, such as poor stunning or
      high levels of bruising, can be easily corrected by management who is committed
      to maintaining high standards. Another concern is biological system overload,
      occurring when animals are bred for more productivity. Researchers and industry
      need to determine optimum production levels instead of maximums. Retailers are
      major drivers of animal welfare standards enforcement and they respond to
      pressure from both activists and consumers. 

PMID- 24928167
TI  - Editor's choice--The effect of supervision on walking distance in patients with
      intermittent claudication: a meta-analysis.
AB  - BACKGROUND: A number of reviews have reported the influence of exercise therapy
      (ET) for the treatment of intermittent claudication (IC). However, a complete
      overview of different types of ET is lacking. The aim of this meta-analysis was
      to study the effect of supervision on walking capacity in patients with IC. It
      was hypothesized that there was a positive treatment effect in relation to the
      intensity of supervision and improvement in walking capacity (i.e., a "dose
      response" hypothesis). METHODS: A systematic search in the Cochrane Central
      Register of Controlled Trials, MEDLINE, and EMBASE databases was performed. Only
      randomized controlled trials (RCTs) evaluating the efficacy of an ET in IC were
      included. Type of supervision, treadmill protocol, length of ET, total training
      volume, and change in walking distance were extracted. RCTs were categorised
      according to type of support: no exercise, walking advice, home-based exercise
      (HB-ET), and supervised exercise therapy (SET). A standardised mean difference
      between pre- and post-training maximal walking distance (MWD) and pain-free
      walking distance (PFWD) was calculated for all subgroups at 6 weeks, and 3 and 6
      months of follow up. RESULTS: Thirty studies involving 1406 patients with IC were
      included. The overall quality was moderate-to-good, although number of included
      patients varied widely (20-304). The intensity of supervision was directly
      related to MWD and PFWD. SET was superior to other conservative treatment
      regimens with respect to improvement in walking distances at all follow-ups.
      However, the difference between HB-ET and SET at 6 months of follow up was not
      significant. CONCLUSION: Supervised exercise therapy for intermittent
      claudication is superior to all other forms of exercise therapy. Intensity of
      supervision is related to improved walking distance.

PMID- 24928169
TI  - Use of animals in research and reporting of animal experiments -- the need for
      improvement.

PMID- 24928168
TI  - Identification and genetic characterization of avian-origin H3N2 canine influenza
      viruses isolated from the Liaoning province of China in 2012.
AB  - A total of 158 serum samples and 510 nasal swab specimens were collected between
      September 2010 and May 2012, from dogs exhibiting respiratory symptoms, in order
      to investigate the epidemiology of H3N2 canine influenza viruses (CIVs) in the
      Liaoning province of China. Serological surveillance demonstrated that 10.8 %
      (17/158) of serum samples were positive for H3N2 canine influenza. Two H3N2
      influenza viruses, A/canine/Liaoning/27/2012 and A/canine/Liaoning/H6/2012, were
      isolated from pet dogs in 2012. Phylogenetic analysis indicated that the genes
      from these two viruses were closely related to those of avian-origin, H3N2
      subtype CIVs from China and Thailand. Genetic analysis of eight genes revealed
      that these two H3N2 canine influenza isolates were highly similar (99.2-99.8 %)
      to the current common strains in Asia. Analysis of the genotype demonstrated that
      each gene of the two strains in this study had the same genotype (K, G, E, 3B, F,
      2D, F, 1E) as those prevalent in H3N2 CIVs. Our findings further confirm that
      avian-origin H3N2 canine influenza has become established in China. Conducting
      extensive serological and epidemiological surveillance is necessary to develop an
      effective vaccine against this disease. 

PMID- 24928170
TI  - Fatal infection with Taenia martis metacestodes in a ring-tailed lemur (Lemur
      catta) living in an Italian zoological garden.
AB  - A case of fatal infection caused by larval forms of Taenia martis in a ring
      tailed lemur (Lemur catta) living in the Rome zoological garden is described. The
      animal, living in a semi-natural pen with other 15 conspecific individuals and
      being fed with fresh fruit and vegetables, yoghurt and eggs, was transported to
      the Istituto Zooprofilattico of Rome for post-mortem examination. The anamnesis
      included, ten days before the death, apathy, lack of appetite, abdominal
      distension and diarrhoea. A severe exudative fibrinous-purulent peritonitis with
      numerous adhesions between the abdominal wall and the bowel loops was detected.
      After intestine removal, two free and viable, 4 cm long, whitish, leaf-like
      parasitic forms were pinpointed. Macroscopic examination of the two parasites
      allowed their identification as larval stages of cestodes, identified via
      molecular analysis as T. martis metacestodes. This report represents the first
      record of T. martis infection in the host species and in a zoological garden and
      for the pathological relevance of the infection.

PMID- 24928172
TI  - The military physician and contested medical humanitarianism: a dueling identity?
AB  - A critical issue in the study of humanitarianism is who counts as a medical
      humanitarian. Military physicians are often characterized as caught between the
      potentially incompatible roles of physician and military professional. Medical
      NGOs, such as Medecins Sans Frontieres (MSF), have also vociferously rejected
      military medical humanitarianism: questioning the mandate, skills, and
      appropriateness of military involvement in humanitarian medicine as well as the
      potential impact on 'humanitarian space'. Yet many military doctors contest this.
      Consequently this study examines the ways in which primarily British military
      physicians identify and manage their identities as both medical humanitarians and
      soldiers. The research utilized a mixed method, grounded theory approach
      involving systematic document searches/expert identification of a core literature
      of 300 policy and peer reviewed documents, plus grey literature and 53 formal
      medical post operational reports from units serving in Iraq and Afghanistan
      between 2004 and 2012. Semi structured interviews involved purposive sampling (34
      respondents) ranging from a former Surgeon General to more junior staff. Methods
      also included an analysis of the original data and literature from the 2003
      Medical Services Delphi study (involving an additional 40 experts and an
      extensive literature review) on military medical identity/future roles as well as
      direct observation of military doctors in Iraq and Afghanistan (two, 2 month
      research trips). The research concluded that military physicians conceived of
      themselves as autonomous medical humanitarians with an individual morality rooted
      in civilian medical ethics that facilitated resistance to the potentially
      hegemonic military identity. Nevertheless military physicians were part of a
      medical organization with fundamentally different priorities from those of
      civilian humanitarian physicians. Furthermore, the perceived emergence of
      multiple civilian 'humanitarianisms' has legitimated a space for the military
      physician alongside other variants of humanitarianism. This study contributes to
      the growing body of work on the self-identity of health professionals as
      humanitarians in conflict settings and demonstrates how the military medical
      identity fits into a fragmented civilian humanitarianism. 

PMID- 24928171
TI  - Providing male rats deficient in iron and n-3 fatty acids with iron and alpha
      linolenic acid alone affects brain serotonin and cognition differently from
      combined provision.
AB  - BACKGROUND: We recently showed that a combined deficiency of iron (ID) and n-3
      fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces
      greater memory deficits than ID or n-3 FAD alone. Providing these double
      deficient rats with either iron (Fe) or preformed docosahexaenoic acid
      (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways
      differently from combined repletion and even exacerbated cognitive deficits
      associated with double-deficiency. Iron is a co-factor of the enzymes responsible
      for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the
      provision of ALA with Fe might be more effective in restoring brain EPA and DHA
      and improving cognition in double-deficient rats than ALA alone. METHODS: In this
      study we examined whether providing double-deficient rats with ALA and Fe, alone
      or in combination, can correct deficits in monoamine metabolism and cognition
      associated with double-deficiency. Using a 2 * 2 design, male rats with
      concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n
      3 FAD diet for 5 weeks (postnatal day 56-91). Biochemical measures, and spatial
      working and reference memory (using the Morris water maze) were compared to age
      matched controls. RESULTS: In the hippocampus, we found a significant Fe * ALA
      interaction on DHA: Compared to the group receiving ALA alone, DHA was
      significantly higher in the Fe + ALA group. In the brain, we found significant
      antagonistic Fe * ALA interactions on serotonin concentrations. Provision of ALA
      alone impaired working memory compared with age-matched controls, while in the
      reference memory task ALA provided with Fe significantly improved performance.
      CONCLUSION: These results indicate that providing either iron or ALA alone to
      double-deficient rats affects serotonin pathways and cognitive performance
      differently from combined provision. This may be partly explained by the
      enhancing effect of Fe on the conversion of ALA to EPA and DHA.

PMID- 24928173
TI  - The in vitro and in vivo profile of aclidinium bromide in comparison with
      glycopyrronium bromide.
AB  - This study characterised the in vitro and in vivo profiles of two novel long
      acting muscarinic antagonists, aclidinium bromide and glycopyrronium bromide,
      using tiotropium bromide and ipratropium bromide as comparators. All four
      antagonists had high affinity for the five muscarinic receptor sub-types (M1-M5);
      aclidinium had comparable affinity to tiotropium but higher affinity than
      glycopyrronium and ipratropium for all receptors. Glycopyrronium dissociated
      faster from recombinant M3 receptors than aclidinium and tiotropium but more
      slowly than ipratropium; all four compounds dissociated more rapidly from M2
      receptors than from M3 receptors. In vitro, aclidinium, glycopyrronium and
      tiotropium had a long duration of action at native M3 receptors (>8 h versus 42
      min for ipratropium). In vivo, all compounds were equi-potent at reversing
      acetylcholine-induced bronchoconstriction. Aclidinium, glycopyrronium and
      ipratropium had a faster onset of bronchodilator action than tiotropium.
      Aclidinium had a longer duration of action than glycopyronnium (time to 50%
      recovery of effect [t1/2 offset] = 29 h and 13 h, respectively); these compare
      with a t1/2 offset of 64 h and 8 h for tiotropium and ipratropium, respectively.
      Aclidinium was less potent than glycopyrronium and tiotropium at inhibiting
      salivation in conscious rats (dose required to produce half-maximal effect [ED50]
      = 38, 0.74 and 0.88 MUg/kg, respectively) and was more rapidly hydrolysed in rat,
      guinea pig and human plasma compared with glycopyrronium or tiotropium. These
      results indicate that while aclidinium and glycopyrronium are both potent
      antagonists at muscarinic receptors with similar kinetic selectivity for M3
      receptors versus M2, aclidinium has a longer dissociation half-life at M3
      receptors and a longer duration of bronchodilator action in vivo than
      glycopyrronium. The rapid plasma hydrolysis of aclidinium, coupled to its kinetic
      selectivity, may confer a reduced propensity for systemic anticholinergic side
      effects with aclidinium versus glycopyrronium and tiotropium. 

PMID- 24928174
TI  - Don't fuel the fire: decreasing intravenous haloperidol use in high risk patients
      via a customized electronic alert.
AB  - Delivering useful clinical decision support to providers who are ordering high
      risk drugs for high risk patients is imperative for safe pharmacotherapy. This
      paper presents a focused electronic clinical decision support intervention
      designed to decrease the risk of corrected QT interval (QTc) related adverse drug
      events in a high risk patient population. Results showed that a customized alert
      can both decrease the number of alerts sent to providers while still improving
      the safety of prescribing practices for intravenous haloperidol. The alert
      leveraged components of the electronic health record to significantly decrease
      the rate of inappropriate prescription of intravenous haloperidol in patients
      with QTc >500 ms from 50% to 14%. The results also suggest providers may abandon
      the appropriate prescription of a medication in response to an alert. The
      findings support the necessity of careful targeting of electronic alerts and
      monitoring for unintended consequences when implementing these types of
      electronic alerts. 

PMID- 24928175
TI  - Tweeting it off: characteristics of adults who tweet about a weight loss attempt.
AB  - OBJECTIVE: The purpose of this study was to describe adults who use Twitter
      during a weight loss attempt and to compare the positive and negative social
      influences they experience from their offline friends, online friends, and family
      members. MATERIALS AND METHODS: Participants (N=100, 80% female, mean age=37.65,
      SD=8.42) were recruited from Twitter. They completed a brief survey about their
      experiences discussing their weight loss attempt with their online and offline
      friends and provided responses to open-ended questions on the benefits and
      drawbacks of discussing weight on Twitter, Facebook, and weight-specific social
      networks. RESULTS: Participants rated their connections on Twitter and weight
      loss-specific social networks to be significantly greater sources of positive
      social influence for their weight loss (F(3)=3.47; p<0.001) and significantly
      lesser sources of negative social influence (F(3)=40.39 and F(3)=33.68 (both
      p<0.001)) than their offline friends, family, and Facebook friends. Greater
      positive social influence from Twitter and Facebook friends was associated with
      greater weight loss in participants' most recent weight loss attempt (r=0.30,
      r=0.32; p<0.01). The most commonly reported benefits of tweeting about weight
      loss include social support, information, and accountability. The most common
      drawbacks reported are that interactions were too brief and lacked personal
      connection. DISCUSSION: People who discuss their weight loss on Twitter report
      more social support and less negativity from their Twitter friends than their
      Facebook friends and in-person relationships. CONCLUSIONS: Online social networks
      should be explored as a tool for connecting patients who lack weight loss social
      support from their in-person relationships.

PMID- 24928176
TI  - Temporal trends of hemoglobin A1c testing.
AB  - OBJECTIVE: The study of utilization patterns can quantify potential overuse of
      laboratory tests and find new ways to reduce healthcare costs. We demonstrate the
      use of distributional analytics for comparing electronic health record (EHR)
      laboratory test orders across time to diagnose and quantify overutilization.
      MATERIALS AND METHODS: We looked at hemoglobin A1c (HbA1c) testing across 119,000
      patients and 15 years of hospital records. We examined the patterns of HbA1c
      ordering before and after the publication of the 2002 American Diabetes
      Association guidelines for HbA1c testing. We conducted analyses to answer three
      questions. What are the patterns of HbA1c ordering? Do HbA1c orders follow the
      guidelines with respect to frequency of measurement? If not, how and why do they
      depart from the guidelines? RESULTS: The raw number of HbA1c orderings has
      steadily increased over time, with a specific increase in low-measurement
      orderings (<6.5%). There is a change in ordering pattern following the 2002
      guideline (p<0.001). However, by comparing ordering distributions, we found that
      the changes do not reflect the guidelines and rather exhibit a new practice of
      rapid-repeat testing. The rapid-retesting phenomenon does not follow the 2009
      guidelines for diabetes diagnosis either, illustrated by a stratified HbA1c value
      analysis. DISCUSSION: Results suggest HbA1c test overutilization, and
      contributing factors include lack of care coordination, unexpected values
      prompting retesting, and point-of-care tests followed by confirmatory laboratory
      tests. CONCLUSIONS: We present a method of comparing ordering distributions in an
      EHR across time as a useful diagnostic approach for identifying and assessing the
      trend of inappropriate use over time.

PMID- 24928178
TI  - More light behind gene expression.
AB  - Light-regulated gene expression, mediated by photoreceptors, acts as a
      multifaceted regulator to control the abundance of functional genes at different
      levels. Two recent genome-wide studies by Wu et al. and Liu et al. show that
      light controls gene expression at post-transcriptional and translational level
      through alternative splicing and translational regulation, respectively. 

PMID- 24928177
TI  - Applying MetaMap to Medline for identifying novel associations in a large
      clinical dataset: a feasibility analysis.
AB  - OBJECTIVE: We describe experiments designed to determine the feasibility of
      distinguishing known from novel associations based on a clinical dataset
      comprised of International Classification of Disease, V.9 (ICD-9) codes from 1.6
      million patients by comparing them to associations of ICD-9 codes derived from
      20.5 million Medline citations processed using MetaMap. Associations appearing
      only in the clinical dataset, but not in Medline citations, are potentially
      novel. METHODS: Pairwise associations of ICD-9 codes were independently
      identified in both the clinical and Medline datasets, which were then compared to
      quantify their degree of overlap. We also performed a manual review of a subset
      of the associations to validate how well MetaMap performed in identifying
      diagnoses mentioned in Medline citations that formed the basis of the Medline
      associations. RESULTS: The overlap of associations based on ICD-9 codes in the
      clinical and Medline datasets was low: only 6.6% of the 3.1 million associations
      found in the clinical dataset were also present in the Medline dataset. Further,
      a manual review of a subset of the associations that appeared in both datasets
      revealed that co-occurring diagnoses from Medline citations do not always
      represent clinically meaningful associations. DISCUSSION: Identifying novel
      associations derived from large clinical datasets remains challenging. Medline as
      a sole data source for existing knowledge may not be adequate to filter out
      widely known associations. CONCLUSIONS: In this study, novel associations were
      not readily identified. Further improvements in accuracy and relevance for tools
      such as MetaMap are needed to realize their expected utility.

PMID- 24928179
TI  - Diversity and ancestry of flatworms infecting blood of nontetrapod craniates
      "fishes".
AB  - We herein review all published molecular studies (life history, taxonomy, and
      phylogeny) and summarize all GenBank sequences and primer sets for the "fish
      blood flukes". Further, by analysing new and all available sequence data for the
      partial D1-D2 domains of 28S from 83 blood fluke taxa, we explore the
      evolutionary expansion of flatworm parasitism in the blood of craniates. Based on
      this analysis, the blood flukes infecting marine bony fishes (Euteleostei) are
      monophyletic. The clade comprising the chondrichthyan blood fluke plus the marine
      euteleost blood flukes is the sister group to tetrapod blood flukes (spirorchiids
      and schistosomes). The innominate blood fluke cercariae from freshwater
      gastropods were monophyletic and sister to the clade comprising spirorchiids and
      schistosomes, but low nodal support indicated that they may represent a distinct
      blood fluke lineage with phylogenetic affinities also to fish blood flukes. Blood
      flukes that utilize gastropod intermediate hosts were monophyletic (unidentified
      gastropod cercariae+tetrapod blood flukes) and those utilizing bivalves and
      polychaetes were monophyletic (marine fish blood flukes). Low or no taxon
      sampling among blood flukes of basal fish lineages and primary division
      freshwater fish lineages are significant data gaps needing closure. We also note
      that no record of an infection exists in a hagfish (Myxiniformes), lamprey
      (Petromyzontiformes), or nontetrapod sarcopterygiian, i.e., coelacanth
      (Coelacanthimorpha) or lungfish (Dipnoi). The present phylogenetic analysis
      reiterated support for monophyly of Schistosomatidae and paraphyly of
      spirorchiids, with the blood flukes of freshwater turtles basal to those of
      marine turtles and schistosomes. 

PMID- 24928180
TI  - Techniques for the diagnosis of Fasciola infections in animals: room for
      improvement.
AB  - The common liver fluke, Fasciola hepatica, causes fascioliasis, a significant
      disease in mammals, including livestock, wildlife and humans, with a major
      socioeconomic impact worldwide. In spite of its impact, and some advances towards
      the development of vaccines and new therapeutic agents, limited attention has
      been paid to the need for practical and reliable methods for the diagnosis of
      infection or disease. Accurate diagnosis is central to effective control,
      particularly given an emerging problem with drug resistance in F. hepatica.
      Traditional coprological techniques have been widely used, but are often
      unreliable. Although there have been some advances in establishing immunologic
      techniques, these tools can suffer from a lack of diagnostic specificity and/or
      sensitivity. Nonetheless, antigen detection tests seem to have considerable
      potential, but have not yet been adequately evaluated in the field. Moreover,
      advanced nucleic acid-based methods appear to offer the most promise for the
      diagnosis of current infection. This chapter (i) provides a brief account of the
      biology and significance of F. hepatica/fascioliasis, (ii) describes key
      techniques currently in use, (iii) compares their advantages/disadvantages and
      (iv) reviews polymerase chain reaction-based methods for specific diagnosis
      and/or the genetic characterization of Fasciola species. 

PMID- 24928181
TI  - Reevaluating the evidence for Toxoplasma gondii-induced behavioural changes in
      rodents.
AB  - The ubiquitous protozoan parasite Toxoplasma gondii has been associated with
      behavioural changes in various hosts, including humans. In rodents, these
      behavioural changes are thought to represent adaptive manipulation by T. gondii
      to enhance transmission from intermediate hosts to the feline definitive host. In
      this review, we have tabulated evidence of changes in motor coordination,
      learning, memory, locomotion, anxiety, response to novelty and aversion to feline
      odour in rodents experimentally infected with T. gondii. In general, there was no
      consistent indication of the direction or magnitude of behavioural changes in
      response to infection. This may be due to the use, in these experimental studies,
      of different T. gondii strains, different host species and sexes and/or different
      methodologies to measure behaviour. A particular problem with studies of
      behavioural manipulation is likely to be the validity of behavioural tests, that
      is, whether they are actually measuring the traits that they were designed to
      measure. We suggest that future studies can be improved in three major ways.
      First, they should use multiple tests of behaviour, followed by multivariate data
      analysis to identify behavioural constructs such as aversion, anxiety and
      response to novelty. Second, they should incorporate longitudinal measurements on
      the behaviour of individual hosts before and after infection, so that within
      individual and between-individual variances and covariances in behavioural traits
      can be estimated. Finally, they should investigate how variables such as parasite
      strain, host species and host sex interact with parasite infection to alter host
      behaviour, in order to provide a sound foundation for research concerning the
      proximate and ultimate mechanism(s) responsible for behavioural changes. 

PMID- 24928183
TI  - Left ventricular diastolic performance at rest is essential for exercise capacity
      in patients with non-complicated myocardial infarction.
AB  - INTRODUCTION: In patients with recent myocardial infarction (MI) limited exercise
      capacity during physical activity is an important symptom and the base for future
      treatment. The myocardial injury after MI leads to both systolic and diastolic
      left ventricular (LV) dysfunction. OBJECTIVE: The aim of this study was to assess
      the relevance of systolic and diastolic LV function for cardiopulmonary exercise
      capacity in patients with prior MI. METHODS: Sixty-five consecutive patients
      after first MI without signs and symptoms of heart failure, aged 52 +/- 6 years,
      were included in the study. The following echo parameters were evaluated: LV
      ejection fraction (LVEF), peak early and late diastolic velocities (E, A),
      deceleration time of E wave (dec t E), ratio of early trans-mitral to early
      annular diastolic velocities (E/e'), velocity propagation of early filling (Vp),
      and diameters and volumes of LV and left atrium (LA). CPET variables included:
      oxygen uptake at peak exercise (peak VO2), oxygen pulse (VO2 HR), VE/VCO2 slope,
      circulatory power (CP) and recovery half time (T1/2). RESULTS: Significant
      correlations were demonstrated between peak VO2 and E/e' (p < 0.001), peak VO2
      and dec t E (p < 0.001), VO2 HR and E/e' (p = 0.002) and between VE/VCO2 and E/e'
      (p < 0.001). Twenty patients with elevated LV filling pressure achieved
      significantly lower peak VO2 (1624 vs. 1932 ml, p = 0.027) VO2 HR (11.70 vs.
      14.05, p = 0.011) and CP (287,073 vs. 361,719, p = 0.014). By using multivariate
      regression model we found that only E/e' (p = 0.001) and dec t E (p = 0.008)
      significantly contributed to peak VO2. CONCLUSIONS: Diastolic dysfunction,
      particularly LV filling pressure, determine exercise capacity, despite
      differences in LV ejection fraction in patients with prior MI.

PMID- 24928184
TI  - Unresolved pulmonary embolism leading to a diagnosis of pulmonary artery sarcoma.
AB  - Pulmonary artery sarcomas (PAS) are rare tumors with a poor prognosis. They are
      often misdiagnosed as pulmonary embolism (PE) leading to futile anticoagulation
      treatment and delay in proper diagnosis. We present a case of a patient who was
      initially misdiagnosed and anticoagulated for presumed pulmonary embolism.
      Progressive symptoms and additional imaging led to the diagnosis of intimal
      pulmonary artery sarcoma for which he underwent surgical resection. This case
      serves as a reminder to consider pulmonary artery sarcoma in the differential
      diagnosis of patients with dyspnea and filling defects on CT pulmonary angiogram
      offering the potential for resection prior to metastasis. 

PMID- 24928185
TI  - Testing a novel pictorial medication sheet to improve adherence in veterans with
      heart failure and cognitive impairment.
AB  - OBJECTIVES: (a) To evaluate efficacy of a pictorial medication sheet to improve
      adherence in veterans with heart failure (HF) and cognitive impairment (CI); (b)
      to describe acceptance of the intervention. BACKGROUND: CI is prevalent in HF and
      is associated with worsened medication adherence. The Veteran's Administration
      has developed a medication image library; however, use of images to improve
      adherence has not been tested. METHODS: Thirty-six veterans with HF and CI were
      enrolled and provided pictorial medication sheets and an optional alarmed
      pillbox. Adherence pre-and post-intervention was determined by 30-day pill
      counts. Acceptance was assessed from interviews. RESULTS: Twenty-seven veterans
      (75%) completed the study. Overall medication adherence was poor, however there
      was significant improvement from pre-intervention (M = 79.74, SD = +/-16.98) to
      post-intervention (M = 84.74, SD = +/-10.00) adherence (t(26) = 2.16, p < .05,
      Cohen's d = .42). CONCLUSIONS: This pilot study provides preliminary evidence
      that medication images improve adherence with complex medication regimens. The
      intervention was well received by patients.

PMID- 24928186
TI  - Positron emission tomography (PET) has limited utility in the staging of
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Positron emission tomography (PET) as an adjunct to conventional
      imaging in the staging of pancreatic adenocarcinoma is controversial. Herein, we
      assess the utility of PET in identifying metastatic disease and evaluate the
      prognostic potential of standard uptake value (SUV). METHODS: Imaging and follow
      up data for patients diagnosed with pancreatic adenocarcinoma were reviewed
      retrospectively. Resectability was assessed based on established criteria, and
      sensitivity, specificity, and accuracy of PET were compared to those of
      conventional imaging modalities. RESULTS: For 123 patients evaluated 2005-2011,
      PET and CT/MRI were concordant in 108 (88 %) cases; however, PET identified
      occult metastatic lesions in seven (5.6 %). False-positive PETs delayed surgery
      for three (8.3 %) patients. In a cohort free of metastatic disease in 78.9 % of
      cases, the sensitivity and specificity of PET for metastases were 89.3 and 85.1
      %, respectively, compared with 62.5 and 93.5 % for CT and 61.5 and 100.0 % for
      MRI. Positive predictive value and negative predictive value of PET were 64.1 and
      96.4 %, respectively, compared with 75.0 and 88.9 % for CT and 100.0 and 91.9 %
      for MRI. Average difference in maximum SUV of resectable and unresectable lesions
      was not statistically significant (5.65 vs. 6.5, p = 0.224) nor was maximum SUV a
      statistically significant predictor of survival (p = 0.18). CONCLUSION: PET is
      more sensitive in identifying metastatic lesions than CT or MRI; however, it has
      a lower specificity, lower positive predictive value, and in some cases, can
      delay definitive surgical management. Therefore, PET has limited utility as an
      adjunctive modality in staging of pancreatic adenocarcinoma.

PMID- 24928187
TI  - Measuring surgical quality: a national clinical registry versus administrative
      claims data.
AB  - BACKGROUND: This study compared postoperative complications of patients who
      underwent pancreaticoduodenectomy (PD) recorded in the National Surgical Quality
      Improvement Program (NSQIP) to patients who underwent PD recorded in the
      Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS).
      METHODS: Data included 8,822 PD cases recorded in NSQIP and 9,827 PD cases
      recorded in NIS performed between 2005 and 2010. Eighteen postoperative adverse
      outcomes were identified in NSQIP and then matched to corresponding International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes
      in NIS. Using logistic regression, the relationship between database and
      postoperative complications was determined while accounting for patient factors.
      RESULTS: Patients undergoing PD in the NIS were more likely to have several
      adverse outcomes, including urinary tract infection (odds ratio (OR) = 1.42, p <
      0.001), pneumonia (OR = 1.51, p < 0.001), renal insufficiency (OR = 2.39, p <
      0.001), renal failure (OR = 1.67, p = 0.005), graft/prosthetic failure (OR =
      9.35, p < 0.001), and longer length of stay (1.1 days, p < 0.001). They were less
      likely to have cardiac arrest (OR = 0.45, p = 0.002), postoperative sepsis (OR =
      0.38, p < 0.001), deep vein thrombosis (OR = 0.18, p < 0.001), and
      cerebrovascular accident (OR = 0.04, p = 0.003). CONCLUSIONS: There is
      considerable discordance between NSQIP and NIS in the assessment of postoperative
      complications following PD, which underscores the value of recognizing the
      capabilities and limitations of each data source.

PMID- 24928188
TI  - FreeSolv: a database of experimental and calculated hydration free energies, with
      input files.
AB  - This work provides a curated database of experimental and calculated hydration
      free energies for small neutral molecules in water, along with molecular
      structures, input files, references, and annotations. We call this the Free
      Solvation Database, or FreeSolv. Experimental values were taken from prior
      literature and will continue to be curated, with updated experimental references
      and data added as they become available. Calculated values are based on
      alchemical free energy calculations using molecular dynamics simulations. These
      used the GAFF small molecule force field in TIP3P water with AM1-BCC charges.
      Values were calculated with the GROMACS simulation package, with full details
      given in references cited within the database itself. This database builds in
      part on a previous, 504-molecule database containing similar information.
      However, additional curation of both experimental data and calculated values has
      been done here, and the total number of molecules is now up to 643. Additional
      information is now included in the database, such as SMILES strings, PubChem
      compound IDs, accurate reference DOIs, and others. One version of the database is
      provided in the Supporting Information of this article, but as ongoing updates
      are envisioned, the database is now versioned and hosted online. In addition to
      providing the database, this work describes its construction process. The
      database is available free-of-charge via
      http://www.escholarship.org/uc/item/6sd403pz . 

PMID- 24928189
TI  - Defining dose-limiting toxicity for phase 1 trials of molecularly targeted
      agents: results of a DLT-TARGETT international survey.
AB  - INTRODUCTION: It is increasingly clear that definitions of dose-limiting toxicity
      (DLT) established for phase 1 trials of cytotoxic agents are not suitable for
      molecularly targeted agents because of specific toxicity profiles. An
      international survey collected expertise on the definition of DLT, as part of an
      initiative aimed at presenting new guidelines for phase 1 trials of targeted
      agents. METHODS: A 15-question survey was sent to corresponding authors of phase
      1 reports. Questions involved: duration of the DLT assessment period,
      incorporation of specific grade 1 (G1) or G2 toxicity and their minimum duration
      to qualify as DLT, exclusion of specific G3 and inclusion of dose
      modification/delay. RESULTS: Among the 400 investigators contacted, 93 replied of
      whom 65 completed the questionnaires. A total of 87% opted for an extended DLT
      assessment period beyond cycle 1, with the proviso not to delay patient accrual.
      Reanalysis at the end of the study of all safety data was proposed in order to
      recommend the phase 2 dose. Most respondents (92%) suggested including dose
      modification in the definition of DLT when dose intensity was decreased to 70%.
      Whilst moderate toxicity was deemed relevant by 70%, the G1/2 toxicities selected
      to define DLT however varied. CONCLUSION: The majority of experts favoured a
      longer DLT assessment period as well as incorporation of specific G2 toxicities
      into the DLT definition. However, no clear consensus existed on a re-definition
      of DLT. Therefore analyses of a large international data warehouse were also used
      to develop guidelines presented in a companion paper.

PMID- 24928190
TI  - Review of therapeutic drug monitoring of anticancer drugs part two--targeted
      therapies.
AB  - Most of oral targeted therapies are tyrosine kinase inhibitors (TKIs). Oral
      administration generates a complex step in the pharmacokinetics (PK) of these
      drugs. Inter-individual PK variability is often large and variability observed in
      response is influenced not only by the genetic heterogeneity of drug targets, but
      also by the pharmacogenetic background of the patient (e.g. cytochome P450 and
      ABC transporter polymorphisms), patient characteristics such as adherence to
      treatment and environmental factors (drug-drug interactions). Retrospective
      studies have shown that targeted drug exposure, reflected in the area under the
      plasma concentration-time curve (AUC) correlates with treatment response
      (efficacy/toxicity) in various cancers. Nevertheless levels of evidence for
      therapeutic drug monitoring (TDM) are however heterogeneous among these agents
      and TDM is still uncommon for the majority of them. Evidence for imatinib
      currently exists, others are emerging for compounds including nilotinib,
      dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin
      (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best
      be reserved for particular situations including lack of therapeutic response,
      severe or unexpected toxicities, anticipated drug-drug interactions and/or
      concerns over adherence treatment. Interpatient PK variability observed with
      monoclonal antibodies (mAbs) is comparable or slightly lower to that observed
      with TKIs. There are still few data with these agents in favour of TDM
      approaches, even if data showed encouraging results with rituximab, cetuximab and
      bevacizumab. At this time, TDM of mAbs is not yet supported by scientific
      evidence. Considerable effort should be made for targeted therapies to better
      define concentration-effect relationships and to perform comparative randomised
      trials of classic dosing versus pharmacokinetically-guided adaptive dosing. 

PMID- 24928191
TI  - Effects of spray and stretch on postneedling soreness and sensitivity after dry
      needling of a latent myofascial trigger point.
AB  - OBJECTIVES: To investigate (1) the effect of spray and stretch versus control on
      reducing postneedling soreness of 1 latent myofascial trigger point (MTrP) and
      (2) whether higher levels of psychological distress are associated with increased
      postneedling pain intensity. DESIGN: A 72-hour follow-up, single-blind randomized
      controlled trial. SETTING: University community. PARTICIPANTS: Healthy volunteers
      (N=70; 40 men, 30 women) aged 18 to 36 years (mean age, 21+/-4y) with latent MTrP
      in 1 upper trapezius muscle. INTERVENTION: All subjects received a dry needling
      application over the upper trapezius muscle. Then, participants were randomly
      divided into 2 groups: an intervention group, which received spray and stretch
      over the needled trapezius muscle, and a control group, which did not receive any
      intervention. MAIN OUTCOME MEASURES: Visual analog scale (at postneedling,
      posttreatment, and 6, 12, 24, 48, and 72h after needling), pressure pain
      threshold (at preneedling, postneedling, and 24 and 48h after needling).
      Psychological distress was evaluated by using the Symptom Checklist-90-Revised.
      RESULTS: Repeated-measures analysis of variance demonstrated a significant
      interaction between group and time (F3,204.8=3.19; P<.05; etap(2)=.04) for
      changes in postneedling soreness. Between-group differences were significant only
      immediately after intervention (P=.002), and there were no differences found
      between groups after 6 hours of the intervention (P>.05). Repeated measures of
      covariance showed that none of the psychological covariates affected these
      results. Somatization, anxiety, interpersonal sensitivity, and hostility were
      significantly correlated (P<.05) with postneedling pain intensity. Repeated
      measures analysis of variance did not show a significant effect of spray and
      stretch on mechanical hyperalgesia (F2.6,175=1.9; P=.131; etap(2)=.02).
      CONCLUSIONS: The spray and stretch had a short-term (<6h) effect in reducing
      postneedling soreness of a latent MTrP. Pressure pain threshold did not
      significantly change after spray and stretch. Psychological factors are related
      to postneedling pain.

PMID- 24928192
TI  - Deoxyribonucleotides as genetic and metabolic regulators.
AB  - For >35 yr, we have known that the accuracy of DNA replication is controlled in
      large part by the relative concentrations of the 4 canonical deoxyribonucleoside
      5'-triphosphates (dNTPs) at the replisome. Since this field was last reviewed, ~8
      yr ago, there has been increased understanding of the mutagenic pathways as they
      occur in living cells. At the same time, aspects of deoxyribonucleotide
      metabolism have been shown to be critically involved in processes as diverse as
      cell cycle control, protooncogene expression, cellular defense against HIV
      infection, replication rate control, telomere length control, and mitochondrial
      function. Evidence supports a relationship between dNTP pools and microsatellite
      repeat instability. Relationships between dNTP synthesis and breakdown in
      controlling steady-state pools have become better defined. In addition, new
      experimental approaches have allowed definitive analysis of mutational pathways
      induced by dNTP pool abnormalities, both in Escherichia coli and in yeast.
      Finally, ribonucleoside triphosphate (rNTP) pools have been shown to be critical
      determinants of DNA replication fidelity. These developments are discussed in
      this review article.

PMID- 24928193
TI  - Taking steps to increase the trustworthiness of scientific research.
AB  - To enjoy the public's trust, the research community must first be clear about
      what it is expected to do and then avoid the incidents that prevent it from
      meeting those expectations. Among other things, there are expectations that
      published scientific results will be reliable, that research has the potential to
      contribute to the common good, and that research will be conducted ethically.
      Consequently, the scientific community needs to avoid lapses that prevent it from
      meeting these three expectations. This requires a strong commitment to
      trustworthy research practices, as well as mechanisms that diminish lapses that
      inevitably occur in complex endeavors such as scientific research. The author
      presents a model to assess the strength of commitment to trustworthy research and
      explores proven quality assurance mechanisms that can diminish lapses in research
      injurious to the public's trust. Some mechanisms identify in advance ways that
      things can go wrong so that steps can be taken to prevent them from going wrong
      in the first place. Other mechanisms investigate past errors or near misses to
      discover their causes so that they can be addressed to avoid similar future
      instances. The author explains why such methods are useful to efforts to promote
      research worthy of the public's trust.

PMID- 24928194
TI  - Sources of error in the retracted scientific literature.
AB  - Retraction of flawed articles is an important mechanism for correction of the
      scientific literature. We recently reported that the majority of retractions are
      associated with scientific misconduct. In the current study, we focused on the
      subset of retractions for which no misconduct was identified, in order to
      identify the major causes of error. Analysis of the retraction notices for 423
      articles indexed in PubMed revealed that the most common causes of error-related
      retraction are laboratory errors, analytical errors, and irreproducible results.
      The most common laboratory errors are contamination and problems relating to
      molecular biology procedures (e.g., sequencing, cloning). Retractions due to
      contamination were more common in the past, whereas analytical errors are now
      increasing in frequency. A number of publications that have not been retracted
      despite being shown to contain significant errors suggest that barriers to
      retraction may impede correction of the literature. In particular, few cases of
      retraction due to cell line contamination were found despite recognition that
      this problem has affected numerous publications. An understanding of the errors
      leading to retraction can guide practices to improve laboratory research and the
      integrity of the scientific literature. Perhaps most important, our analysis has
      identified major problems in the mechanisms used to rectify the scientific
      literature and suggests a need for action by the scientific community to adopt
      protocols that ensure the integrity of the publication process.

PMID- 24928195
TI  - Intestinal deletion of leptin signaling alters activity of nutrient transporters
      and delayed the onset of obesity in mice.
AB  - The importance of B-isoform of leptin receptor (LEPR-B) signaling in the
      hypothalamus, pancreas, or liver has been well characterized, but in the
      intestine, a unique site of entry for dietary nutrition into the body, it has
      been relatively ignored. To address this question, we characterized a mouse model
      deficient for LEPR-B specifically in intestinal epithelial cells (IECs).
      (IEC)LEPR-B-knockout (KO) and wild-type (WT) mice were generated by Cre-Lox
      strategy and fed a normal or high-fat diet (HFD). The analyses of the animals
      involved histology and immunohistochemistry of intestinal mucosa, indirect
      calorimetric measurements, whole-body composition, and expression and activities
      of nutrient transporters. (IEC)LEPR-B-KO mice exhibited a 2-fold increase in
      length of jejunal villi and have normal growth on a normal diet but were less
      susceptible (P<0.01) to HFD-induced obesity. No differences occurred in energy
      intake and expenditure between (IEC)LEPR-B-WT and -KO mice, but (IEC)LEPR-B-KO
      mice fed an HFD showed increased excreted fats (P<0.05). Activities of the
      Na(+)/glucose cotransporter SGLT-1 and GLUT2 were unaffected in LEPR-B-KO
      jejunum, while GLUT5-mediated fructose transport and PepT1-mediated peptide
      transport were substantially reduced (P<0.01). These data demonstrate that
      intestinal LEPR-B signaling is important for the onset of diet-induced obesity.
      They suggest that intestinal LEPR-B could be a potential per os target for
      prevention against obesity.

PMID- 24928196
TI  - Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet
      fed dams are not "reprogrammed" by regular chow diet in rats.
AB  - This study aimed to determine whether epigenetic malprogramming induced by high
      fat diet (HFD) has an obesogenic effect on nonmated and mated female rats and
      their offspring. Further, it aimed to reprogram offspring's epigenetic
      malprogramming and phenotype by providing normal diet after weaning. Body weight
      (BW) was measured, and plasma and hypothalamic arcuate nuclei were collected for
      analysis of hormones, mRNA, and DNA CpG methylation of the promoter of Pomc, a
      key factor in control of food intake. In nonmated females, HFD decreased
      Pomc/leptin ratio by ~38%. This finding was associated with Pomc promoter
      hypermethylation. While heavier during pregnancy, during lactation HFD dams
      showed sharper BW decrease (2.5-fold) and loss of Pomc promoter hypermethylation.
      Moreover, their weight loss was correlated with demethylation (r=-0.707) and with
      gadd45b mRNA expression levels (r=0.905). Even though offspring of HFD dams ate
      standard chow from weaning, they displayed increased BW, Pomc promoter
      hypermethylation, and vulnerability to HFD challenge (3-fold kilocalorie intake
      increase). These findings demonstrate a long-term effect of maternal HFD on CpG
      methylation of the Pomc promoter in the offspring, which was not reprogrammed by
      standard chow from weaning. Further, the results suggest a possible mechanism of
      demethylation of the Pomc promoter following pregnancy and lactation.

PMID- 24928197
TI  - Diminished skeletal muscle microRNA expression with aging is associated with
      attenuated muscle plasticity and inhibition of IGF-1 signaling.
AB  - Older individuals have a reduced capacity to induce muscle hypertrophy with
      resistance exercise (RE), which may contribute to the age-induced loss of muscle
      mass and function, sarcopenia. We tested the novel hypothesis that dysregulation
      of microRNAs (miRNAs) may contribute to reduced muscle plasticity with aging.
      Skeletal muscle expression profiling of protein-coding genes and miRNA was
      performed in younger (YNG) and older (OLD) men after an acute bout of RE. 21
      miRNAs were altered by RE in YNG men, while no RE-induced changes in miRNA
      expression were observed in OLD men. This striking absence in miRNA regulation in
      OLD men was associated with blunted transcription of mRNAs, with only 42 genes
      altered in OLD men vs. 175 in YNG men following RE, demonstrating a reduced
      adaptability of aging muscle to exercise. Integrated bioinformatics analysis
      identified miR-126 as an important regulator of the transcriptional response to
      exercise and reduced lean mass in OLD men. Manipulation of miR-126 levels in
      myocytes, in vitro, revealed its direct effects on the expression of regulators
      of skeletal muscle growth and activation of insulin growth factor 1 (IGF-1)
      signaling. This work identifies a mechanistic role of miRNA in the adaptation of
      muscle to anabolic stimulation and reveals a significant impairment in exercise
      induced miRNA/mRNA regulation with aging.

PMID- 24928199
TI  - Obesity, hypertension and diabetes mellitus affect complication rate of different
      nephrectomy techniques.
AB  - INTRODUCTION: To investigate whether obesity, hypertension, and diabetes mellitus
      (DM) would increase post-nephrectomy complication rates using standardized
      classification method. METHODS: We retrospectively included 843 patients from
      March 2006 to November 2012, of whom 613 underwent radical nephrectomy (RN) and
      229 had partial nephrectomy (PN). Modified Clavien classification system was
      applied to quantify complication severity of nephrectomy. Fisher's exact or chi
      square test was used to assess the relationship between complication rates and
      obesity, hypertension, as well as DM. RESULTS: The prevalence of obesity,
      hypertension, and DM was 11.51%, 30.84%, 8.78%, respectively. The overall
      complication rate was 19.31%, 30.04%, 35.71% and 36.36% for laparoscopic radical
      nephrectomy (LRN), open-RN, LPN and open-PN respectively. An increasing trend of
      low grade complication rate as BMI increased was observed in LRN (P=.027) and
      open-RN (P<.001). Obese patients had greater chance to have low grade
      complications in LRN (OR=4.471; 95% CI: 1.290-17.422; P=0.031) and open-RN
      (OR=2.448; 95% CI: 1.703-3.518; P<.001). Patients with hypertension were more
      likely to have low grade complications, especially grade ii complications in open
      RN (OR=1.526; 95% CI: 1.055-2.206; P=.026) and open PN (OR=2.032; 95% CI: 1.199
      3.443; P=.009). DM was also associated with higher grade i complication rate in
      open-RN (OR=2.490; 95% CI: 331-4.657; P=.016) and open-PN (OR=4.425; 95% CI:
      1.815-10.791; P=.013). High grade complication rates were similar in comparison.
      CONCLUSIONS: Obesity, hypertension, and DM were closely associated with increased
      post-nephrectomy complication rates, mainly low grade complications.

PMID- 24928198
TI  - RLIP76 regulates HIF-1 activity, VEGF expression and secretion in tumor cells,
      and secretome transactivation of endothelial cells.
AB  - This study was undertaken to reveal the mechanisms by which RLIP76 regulates
      endothelial cell angiogenic responses. RLIP76 is an effector of the angiogenic
      modulator, R-Ras. RLIP76 is overexpressed in many tumors, required for tumor
      angiogenesis, and blockade of RLIP76 results in tumor regression in multiple
      models. We report here that RLIP76 was required for expression and secretion of
      vascular endothelial growth factor (VEGF) in carcinoma and melanoma cells.
      Conditioned medium derived from RLIP76-depleted tumor cells, but not control
      knockdown cells, could not stimulate proliferation, migration, or Matrigel cord
      formation in endothelial cell cultures, which indicates that RLIP76 regulates
      angiogenic components of the tumor cell secretome. Recombinant VEGF added to
      conditioned medium from RLIP76-knockdown tumor cells restored these endothelial
      cell functions. Transcriptional activity of hypoxia-inducible factor 1 (HIF-1),
      which drives VEGF expression, was blocked in RLIP76-depleted tumor cells. RLIP76
      was required for PI3-kinase activation, known to regulate HIF-1, in these cells.
      However, HIF-1alpha expression and nuclear localization were unaffected by RLIP76
      knockdown, which suggests that RLIP76 regulates HIF-1 at the functional level.
      Thus, RLIP76 regulates tumor cell transactivation of endothelial cells via
      control of VEGF expression and secretion, providing a new important link in the
      mechanism of tumor cell induction of angiogenesis.

PMID- 24928200
TI  - Combining De Ley-Doudoroff and methylerythritol phosphate pathways for enhanced
      isoprene biosynthesis from D-galactose.
AB  - An engineered Escherichia coli strain was developed for enhanced isoprene
      production using D-galactose as substrate. Isoprene is a valuable compound that
      can be biosynthetically produced from pyruvate and glyceraldehyde-3-phosphate
      (G3P) through the methylerythritol phosphate pathway (MEP). The Leloir and De Ley
      Doudoroff (DD) pathways are known existing routes in E. coli that can supply the
      MEP precursors from D-galactose. The DD pathway was selected as it is capable of
      supplying equimolar amounts of pyruvate and G3P simultaneously. To exclusively
      direct D-galactose toward the DD pathway, an E. coli DeltagalK strain with
      blocked Leloir pathway was used as the host. To obtain a fully functional DD
      pathway, a dehydrogenase encoding gene (gld) was recruited from Pseudomonas
      syringae to catalyze D-galactose conversion to D-galactonate. Overexpressions of
      endogenous genes known as MEP bottlenecks, and a heterologous gene, were
      conducted to enhance and enable isoprene production, respectively. Growth test
      confirmed a functional DD pathway concomitant with equimolar generation of
      pyruvate and G3P, in contrast to the wild-type strain where G3P was limiting.
      Finally, the engineered strain with combined DD-MEP pathway exhibited the highest
      isoprene production. This suggests that the equimolar pyruvate and G3P pools
      resulted in a more efficient carbon flux toward isoprene production. This
      strategy provides a new platform for developing improved isoprenoid producing
      strains through the combined DD-MEP pathway. 

PMID- 24928201
TI  - 4R-cembranoid protects against diisopropylfluorophosphate-mediated
      neurodegeneration.
AB  - Many organophosphorous esters synthesized for applications in industry,
      agriculture, or warfare irreversibly inhibit acetylcholinesterase, and acute
      poisoning with these compounds causes life-threatening cholinergic
      overstimulation. Following classical emergency treatment with atropine, an oxime,
      and a benzodiazepine, surviving victims often suffer brain neurodegeneration.
      Currently, there is no pharmacological treatment to prevent this brain injury.
      Here we show that a cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene
      4,6-diol (4R) ameliorates the damage caused by diisopropylfluorophosphate (DFP)
      in the hippocampal area CA1. DFP has been frequently used as a surrogate for the
      warfare nerve agent sarin. In rats, DFP is lethal at the dose used to cause brain
      damage. Therefore, to observe brain damage in survivors, the death rate was
      reduced by pre-administration of the peripherally acting antidotes pyridostigmine
      and methyl atropine or its analog ipratropium. Pyridostigmine bromide, methyl
      atropine nitrate, and ipratropium bromide were dissolved in saline and injected
      intramuscularly at 0.1mg/kg, 20mg/kg, and 23mg/kg, respectively. DFP (9mg/kg)
      dissolved in cold water was injected intraperitoneally. 4R (6mg/kg) dissolved in
      DMSO was injected subcutaneously, either 1h before or 5 or 24h after DFP.
      Neurodegeneration was assessed with Fluoro-Jade B and amino cupric silver
      staining; neuroinflammation was measured by the expression of nestin, a marker of
      activated astrocytes. Forty-eight hours after DFP administration, 4R decreased
      the number of dead neurons by half when injected before or after DFP. 4R also
      significantly decreased the number of activated astrocytes. These data suggest
      that 4R is a promising new drug that could change the therapeutic paradigm for
      acute poisoning with organophosphorous compounds by the implementation of a
      second-stage intervention after the classical countermeasure treatment. 

PMID- 24928202
TI  - A sore spot: central or peripheral generation of chronic neuropathic spontaneous
      pain?

PMID- 24928203
TI  - Pre-activated blood platelets and a pro-thrombotic phenotype in APP23 mice
      modeling Alzheimer's disease.
AB  - Platelet activation and thrombus formation play a critical role in primary
      hemostasis but also represent a pathophysiological mechanism leading to acute
      thrombotic vascular occlusions. Besides, platelets modulate cellular processes
      including inflammation, angiogenesis and neurodegeneration. On the other hand,
      platelet activation and thrombus formation are altered in different diseases
      leading to either bleeding complications or pathological thrombus formation. For
      many years platelets have been considered to play a role in neuroinflammatory
      diseases such as Alzheimer's disease (AD). AD is characterized by deposits of
      amyloid-beta (Abeta) and strongly related to vascular diseases with platelets
      playing a critical role in the progression of AD because exposure of platelets to
      Abeta induces platelet activation, platelet Abeta release, and enhanced platelet
      adhesion to collagen in vitro and at the injured carotid artery in vivo. However,
      the molecular mechanisms and the relation between vascular pathology and amyloid
      beta plaque formation in the pathogenesis of AD are not fully understood.
      Compelling evidence is suggestive for altered platelet activity in AD patients.
      Thus we analyzed platelet activation and thrombus formation in aged AD transgenic
      mice (APP23) known to develop amyloid-beta deposits in the brain parenchyma and
      cerebral vessels. As a result, platelets are in a pre-activated state in blood of
      APP23 mice and showed strongly enhanced integrin activation, degranulation and
      spreading kinetics on fibrinogen surfaces upon stimulation. This enhanced
      platelet signaling translated into almost unlimited thrombus formation on
      collagen under flow conditions in vitro and accelerated vessel occlusion in vivo
      suggesting that these mice are at high risk of arterial thrombosis leading to
      cerebrovascular and unexpectedly to cardiovascular complications that might be
      also relevant in AD patients.

PMID- 24928204
TI  - Formation of singlet oxygen and protection against its oxidative damage in
      Photosystem II under abiotic stress.
AB  - Photosystem II (PSII) is exposed to various abiotic stresses associated with
      adverse environmental conditions such as high light, heat, heavy metals or
      mechanical injury. Distinctive functional response to adverse environmental
      conditions is formation of singlet oxygen ((1)O2). In this review, recent
      progress on mechanistic principles on (1)O2 formation under abiotic stresses is
      summarized. Under high light, (1)O2 is formed by excitation energy transfer from
      triplet chlorophylls to molecular oxygen formed by the spin conversion via
      photosensitization Type II reaction in the PSII antenna complex or by the
      recombination of (1)[P680(+)Pheo(-)] radical pair in the PSII reaction center.
      Apart from well-described (1)O2 formation by excitation energy transfer, (1)O2
      formation by decomposition of dioxetane and tetroxide is summarized as a
      potential source of (1)O2 in PSII under heat, heavy metals and mechanical stress.
      The description of mechanistic principles on (1)O2 formation under abiotic stress
      allows us to understand how plants respond to adverse environmental conditions in
      vivo. 

PMID- 24928206
TI  - Influence of birth weight and gender on lipid status and adipose tissue gene
      expression in lambs.
AB  - Intrauterine growth restriction (IUGR) is a risk factor for obesity, particularly
      when offspring are born into an unrestricted nutritional environment. In this
      study, we investigated the impact of IUGR and gender on circulating lipids and on
      expression of adipogenic, lipogenic and adipokine genes in perirenal adipose
      tissue. Singleton lambs born to overnourished adolescent dams were normal birth
      weight (N) or IUGR (32% lower birth weight due to placental insufficiency). IUGR
      lambs exhibited increased fractional growth rates but remained smaller than N
      lambs at necropsy (d77). At 48 days, fasting plasma triglycerides, non-esterified
      fatty acids and glycerol were elevated predominantly in IUGR males. Body fat
      content was independent of prenatal growth but higher in females than in males.
      In perirenal fat, relative to male lambs, females had larger adipocytes; higher
      lipoprotein lipase, fatty acid synthase and leptin and lower IGF1, IGF2, IGF1R,
      IGF2R and hormone-sensitive lipase mRNA expression levels, and all were
      independent of prenatal growth category; peroxisome proliferator-activated
      receptor gamma and glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression
      were not affected by IUGR or gender. Adiposity indices were inversely related to
      G3PDH mRNA expression, and for the population as a whole the expression of IGF
      system genes in perirenal fat was negatively correlated with plasma leptin, fat
      mass and adipocyte size, and positively correlated with circulating IGF1 levels.
      Higher plasma lipid levels in IUGR males may predict later adverse metabolic
      health and obesity, but in early postnatal life gender has the dominant influence
      on adipose tissue gene expression, reflecting the already established sexual
      dimorphism in body composition. 

PMID- 24928205
TI  - The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage
      response and autophagy in cancer cells.
AB  - Chemotherapy- or radiotherapy-induced DNA damage activates the Chk1-dependent DNA
      damage response (DDR) and cell cycle checkpoints to facilitate cell survival.
      Numerous attempts have been made to identify specific Chk1 inhibitors to enhance
      the efficiency of chemotherapy or radiotherapy. In this study, we investigated
      the molecular mechanisms underlying the antitumor activity of LY2603618, a potent
      and selective small molecule inhibitor of Chk1 protein kinase, in human lung
      cancer cells. Treatment of cancer cells with LY2603618 caused cell cycle arrest
      in the G2/M phase. A marked induction of DDR, including the phosphorylation of
      ATM, Chk2, p53 and histone H2AX, was observed after LY2603618 treatment.
      LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage
      mediated Chk1 phosphorylation (S345 Chk1). In addition, LY2603618-treated lung
      cancer cells transitioned from LC3-I to LC3-II, a hallmark of autophagy. Blocking
      autophagy with chloroquine (CQ) further enhanced LY2603618's inhibitory effect on
      cell viability/proliferation. LY2603618 also significantly increased p38 and c
      Jun N-terminal kinase (JNK) phosphorylation. Pretreatment with the JNK inhibitor
      reduced cleavage of caspase-3 and PARP levels in LY2603618-treated cells. These
      results suggest the following: (i) the biological consequences of LY2603618 in
      lung cancer cells is associated with both inhibition of Chk1 phosphorylation on
      S296 and activation of the DNA damage response network; and (ii) the anticancer
      property of LY2603618 might be increased by inhibiting autophagy. 

PMID- 24928207
TI  - Molecular mechanisms involved in mammalian primary sex determination.
AB  - Sex determination refers to the developmental decision that directs the
      bipotential genital ridge to develop as a testis or an ovary. Genetic studies on
      mice and humans have led to crucial advances in understanding the molecular
      fundamentals of sex determination and the mutually antagonistic signaling
      pathway. In this review, we summarize the current molecular mechanisms of sex
      determination by focusing on the known critical sex determining genes and their
      related signaling pathways in mammalian vertebrates from mice to humans. We also
      discuss the underlying delicate balance between testis and ovary sex
      determination pathways, concentrating on the antagonisms between major sex
      determining genes. 

PMID- 24928209
TI  - NetBioV: an R package for visualizing large network data in biology and medicine.
AB  - SUMMARY: NetBioV (Network Biology Visualization) is an R package that allows the
      visualization of large network data in biology and medicine. The purpose of
      NetBioV is to enable an organized and reproducible visualization of networks by
      emphasizing or highlighting specific structural properties that are of biological
      relevance. AVAILABILITY AND IMPLEMENTATION: NetBioV is freely available for
      academic use. The package has been tested for R 2.14.2 under Linux, Windows and
      Mac OS X. It is available from Bioconductor.

PMID- 24928208
TI  - Neuropathic pain in osteoarthritis: a review of pathophysiological mechanisms and
      implications for treatment.
AB  - OBJECTIVES: Osteoarthritis (OA) is the leading cause of musculoskeletal pain and
      functional disability worldwide, affecting a growing number of individuals in the
      western society. Despite various conservative and interventional treatment
      approaches, the overall management of the condition is problematic, and pain-the
      major clinical problem of the disease-remains sub-optimally controlled. The
      objectives of this review are to present the pathophysiologic mechanisms
      underlying the complexity of pain in OA and to discuss the challenges for new
      treatment strategies aiming to translate experimental findings into daily
      clinical practice. METHODS: A narrative literature review of studies
      investigating the existence of a neuropathic component in OA pain was conducted.
      We searched PubMed, Embase and Scopus for English language publications. A hand
      search of reference lists of relevant studies was also performed. RESULTS: Recent
      advances have shed additional light on the pathophysiology of osteoarthritic
      pain, highlighting the contribution of central pain pathways together with the
      sensitisation of peripheral joint receptors and changes of the nociceptive
      process induced by local joint inflammation and structural bone tissue changes.
      Thus, a neuropathic pain component may be predominant in individuals with minor
      joint changes but with high levels of pain refractory to analgesic treatment,
      providing an alternative explanation for osteoarthritic pain perception.
      CONCLUSION: A growing amount of evidence suggests that the pain in OA has a
      neuropathic component in some patients. The deeper understanding of multiple
      mechanisms of OA pain has led to the use of centrally acting medicines that may
      have a benefit on alleviating osteoarthritic pain. The ineffective pain
      management and the increasing rates of disability associated with OA mandate for
      change in our treatment paradigm.

PMID- 24928210
TI  - Detecting differential protein expression in large-scale population proteomics.
AB  - MOTIVATION: Mass spectrometry (MS)-based high-throughput quantitative proteomics
      shows great potential in large-scale clinical biomarker studies, identifying and
      quantifying thousands of proteins in biological samples. However, there are
      unique challenges in analyzing the quantitative proteomics data. One issue is
      that the quantification of a given peptide is often missing in a subset of the
      experiments, especially for less abundant peptides. Another issue is that
      different MS experiments of the same study have significantly varying numbers of
      peptides quantified, which can result in more missing peptide abundances in an
      experiment that has a smaller total number of quantified peptides. To detect as
      many biomarker proteins as possible, it is necessary to develop bioinformatics
      methods that appropriately handle these challenges. RESULTS: We propose a
      Significance Analysis for Large-scale Proteomics Studies (SALPS) that handles
      missing peptide intensity values caused by the two mechanisms mentioned above.
      Our model has a robust performance in both simulated data and proteomics data
      from a large clinical study. Because varying patients' sample qualities and
      deviating instrument performances are not avoidable for clinical studies
      performed over the course of several years, we believe that our approach will be
      useful to analyze large-scale clinical proteomics data. AVAILABILITY AND
      IMPLEMENTATION: R codes for SALPS are available at
      http://www.stanford.edu/%7eclairesr/software.html.

PMID- 24928211
TI  - BioBlend.objects: metacomputing with Galaxy.
AB  - SUMMARY: BioBlend.objects is a new component of the BioBlend package, adding an
      object-oriented interface for the Galaxy REST-based application programming
      interface. It improves support for metacomputing on Galaxy entities by providing
      higher-level functionality and allowing users to more easily create programs to
      explore, query and create Galaxy datasets and workflows. AVAILABILITY AND
      IMPLEMENTATION: BioBlend.objects is available online at
      https://github.com/afgane/bioblend. The new object-oriented API is implemented by
      the galaxy/objects subpackage.

PMID- 24928212
TI  - Aortic stiffness is an indicator of cognitive dysfunction before and after aortic
      valve replacement for aortic stenosis.
AB  - OBJECTIVES: Post-cardiac surgical cognitive dysfunction occurs more commonly
      following valvular procedures. Cognitive function has been related to vascular
      health status; however, the relation between pre-existent arterial stiffness and
      perioperative cognitive dysfunction is yet to be defined. The objective of this
      study was to assess whether aortic stiffness is related to cognitive dysfunction
      in surgical aortic stenosis (AS) pre- and postoperatively. METHODS: Between June
      2010 and August 2012, patients undergoing aortic valve replacement (AVR) for AS
      were recruited for inclusion in this prospective observational study. Aortic
      pulse wave velocity (PWV) was used as a measure of aortic stiffness and cognitive
      function was assessed using the computerized Cambridge Neuropsychological Test
      Automated Battery (CANTAB) preoperatively and (409 +/- 159 days) post-AVR.
      RESULTS: Fifty-six patients (age 71 +/- 8.4 years) were recruited. Of the total,
      50 (89%) completed postoperative follow-up. Pre- and postoperatively, patients
      with normal PWV (PWV-norm) had significantly superior delayed memory, sustained
      visual attention and executive function compared with those with high PWV (PWV
      high). Immediate memory and decision-making were similar between groups.
      Postoperatively, improvement in cognitive function was more marked in PWV-high
      compared with PWV-norm patients. In two models of multiple regression analysis,
      PWV as a continuous variable was independently related to all preoperative main
      cognitive components as well as postoperative executive function. PWV as a
      dichotomous variable was independently related to all pre- and postoperative main
      cognitive function components. CONCLUSIONS: AVR may not be associated with an
      independent or homogeneous effect on cognitive decline. Aortic PWV might be
      useful as an additional indicator for cognitive dysfunction before and after
      surgical intervention for AS.

PMID- 24928213
TI  - Effects of specified performance criterion and performance feedback on staff
      behavior: a component analysis.
AB  - The present study isolated the effects of frequently used staff training
      intervention components to increase communication between direct care staff and
      clinicians working on an inpatient behavioral unit. Written "protocol review"
      quizzes developed by clinicians were designed to assess knowledge about a
      patient's behavioral protocols. Direct care staff completed these at the
      beginning of each day and evening shift. Clinicians were required to score and
      discuss these protocol reviews with direct care staff for at least 75% of shifts
      over a 2-week period. During baseline, only 21% of clinicians met this
      requirement. Completing and scoring of protocol reviews did not improve following
      additional in-service training (M = 15%) or following an intervention aimed at
      decreasing response effort combined with prompting (M = 28%). After implementing
      an intervention involving specified performance criterion and performance
      feedback, 86% of clinicians reached the established goal. Results of a component
      analysis suggested that the presentation of both the specified performance
      criterion and supporting contingencies was necessary to maintain acceptable
      levels of performance. 

PMID- 24928214
TI  - Intermediate and C-terminal regions of leptospiral adhesin Lsa66 are responsible
      for binding with plasminogen and extracellular matrix components.
AB  - Leptospirosis, a worldwide zoonotic infection, is an important human and
      veterinary health problem. We have previously identified a leptospiral
      multipurpose adhesin, Lsa66, capable of binding extracellular matrix (ECM)
      components and plasminogen (PLG). In this work, we report the cloning,
      expression, purification and characterization of three fragments derived from the
      full-length Lsa66: N-terminal, intermediate and C-terminal regions. We employed
      Escherichia coli BL21-SI as expression cells. The recombinant fragments tagged
      with N-terminal His6 were purified by metal-charged chromatography to major
      protein bands that were recognized by anti-His-tag mAbs. The recombinant
      fragments were evaluated for their capacity to attach to ECM components and to
      PLG. The intermediate region bound to laminin, plasma fibronectin and PLG.
      Laminin also bound to the C-terminal region. Antibodies in leptospirosis-positive
      serum samples recognized Lsa66, being the immune epitopes located at the N
      terminal and intermediate fragments. The data confirm that Lsa66 is expressed
      during infection and that this protein might have a role in bacterial infection. 

PMID- 24928215
TI  - A Galleria mellonella infection model reveals double and triple antibiotic
      combination therapies with enhanced efficacy versus a multidrug-resistant strain
      of Pseudomonas aeruginosa.
AB  - The aim of this study was to compare the inhibitory effect of antibiotic
      combinations in vitro with efficacy in Galleria mellonella larvae in vivo to
      identify efficacious combinations that target Pseudomonas aeruginosa. P.
      aeruginosa NCTC 13437, a multidrug-resistant strain resistant to beta-lactams and
      aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem,
      amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was
      measured in vitro via a 24 h time-kill assay. In vitro results were then compared
      with the efficacy of the same dual or triple antibiotic combinations versus G.
      mellonella larvae infected with P. aeruginosa. G. mellonella haemolymph burden of
      P. aeruginosa was determined over 96 h post-infection and treatment with the most
      potent combination therapies. Many dual and triple combinations of antibiotics
      displayed synergistic inhibition of multidrug-resistant P. aeruginosa in vitro.
      There was little correlation between combinations that were synergistic in vitro
      and those that showed enhanced efficacy in vivo versus infected G. mellonella
      larvae. The most potent dual and triple combinations in vivo were cefotaxime plus
      piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer
      combinations were found to offer enhanced therapeutic benefit in vivo compared
      with in vitro. The therapeutic benefit arising from treatment with antibiotic
      combinations in vivo correlated with reduced larval burden of P. aeruginosa. This
      study has identified antibiotic combinations that merit further investigation for
      their clinical potential and has demonstrated the utility of using G. mellonella
      to screen for novel antibiotic treatments that demonstrate efficacy in vivo. 

PMID- 24928216
TI  - Epidemiology and microbiology of Shiga toxin-producing Escherichia coli other
      than serogroup O157 in England, 2009-2013.
AB  - The implementation of direct testing of clinical faecal specimens for
      gastrointestinal (GI) pathogens by PCR offers a sensitive and comprehensive
      approach for the detection of Shiga toxin-producing Escherichia coli (STEC). The
      introduction of a commercial PCR assay, known as GI PCR, for the detection of GI
      pathogens at three frontline hospital laboratories in England between December
      2012 and December 2013 led to a significant increase in detection of STEC other
      than serogroup O157 (non-O157 STEC). In 2013, 47 isolates were detected in
      England, compared with 57 in the preceding 4 years (2009-2012). The most common
      non-O157 STEC serogroup detected was O26 (23.2 %). A total of 47 (47.5 %) STEC
      isolates had stx2 only, 28 (28.3 %) carried stx1 and stx2, and the remaining 24
      (24.2 %) had stx1 only. Stx2a (64.0 %) was the most frequently detected Stx2
      subtype. The eae (intimin) gene was detected in 52 (52.5 %) non-O157 STEC
      isolates. Six strains of STEC O104 had aggR, but this gene was not detected in
      any other STEC serogroups in this study. Haemolytic ureamic syndrome was
      significantly associated with STEC strains possessing eae [odds ratio (OR) 5.845,
      P = 0.0235] and/or stx2a (OR 9.56, P = 0.0034) subtypes. A matched case-control
      analysis indicated an association between non-O157 STEC cases and contact with
      farm animals. Widespread implementation of the PCR approach in England will
      determine the true incidence of non-O157 STEC infection, highlight the burden in
      terms of morbidity and mortality, and facilitate the examination of risk factors
      to indicate whether there are niche risk exposures for particular strains. 

PMID- 24928217
TI  - SLIMMER: a randomised controlled trial of diabetes prevention in Dutch primary
      health care: design and methods for process, effect, and economic evaluation.
AB  - BACKGROUND: Implementation of interventions in real-life settings requires a
      comprehensive evaluation approach. The aim of this article is to describe the
      evaluation design of the SLIMMER diabetes prevention intervention in a Dutch real
      life setting. METHODS/DESIGN: The SLIMMER study is a randomised, controlled
      intervention study including subjects aged 40 through 70 years with impaired
      fasting glucose or high risk of diabetes. The 10-month SLIMMER intervention
      involves a dietary and physical activity intervention, including case management
      and a maintenance programme. The control group receives usual health care and
      written information about a healthy lifestyle. A logic model of change is
      composed to link intervention activities with intervention outcomes in a logical
      order. Primary outcome is fasting insulin. Measurements are performed at baseline
      and after 12 and 18 months and cover quality of life, cardio-metabolic risk
      factors (e.g. glucose tolerance, serum lipids, body fatness, and blood pressure),
      eating and physical activity behaviour, and behavioural determinants. A process
      evaluation gives insight in how the intervention was delivered and received by
      participants and health care professionals. The economic evaluation consists of a
      cost-effectiveness analysis and a cost-utility analysis. Costs are assessed from
      both a societal and health care perspective. DISCUSSION: This study is expected
      to provide insight in the effectiveness, including its cost-effectiveness, and
      delivery of the SLIMMER diabetes prevention intervention conducted in Dutch
      primary health care. Results of this study provide valuable information for
      primary health care professionals, researchers, and policy makers. TRIAL
      REGISTRATION: The SLIMMER study is registered with ClinicalTrials.gov
      (NCT02094911) since March 19, 2014.

PMID- 24928218
TI  - Rationale and design of a randomized controlled trial of varenicline directly
      observed therapy delivered in methadone clinics.
AB  - BACKGROUND: Tobacco cessation medication adherence is one of the few factors
      shown to improve smoking cessation rates among methadone-maintained smokers, but
      interventions to improve adherence to smoking cessation medications have not yet
      been tested among methadone treatment patients. Methadone clinic-based, directly
      observed therapy (DOT) programs for HIV and tuberculosis improve adherence and
      clinical outcomes, but have not been evaluated for smoking cessation. We describe
      a randomized controlled trial to evaluate whether a methadone clinic-based,
      directly observed varenicline therapy program increases adherence and tobacco
      abstinence among opioid-dependent drug users receiving methadone treatment.
      METHODS/DESIGN: We plan to enroll 100 methadone-maintained smokers and randomize
      them to directly observed varenicline dispensed with daily methadone doses or
      treatment as usual (self-administered varenicline) for 12 weeks. Our outcome
      measures are: 1) pill count adherence and 2) carbon monoxide-verified tobacco
      abstinence. We will assess differences in adherence and abstinence between the
      two treatment arms using repeated measures models. DISCUSSION: This trial will
      allow for rigorous evaluation of the efficacy of methadone clinic-based, directly
      observed varenicline for improving adherence and smoking cessation outcomes. This
      detailed description of trial methodology can serve as a template for the
      development of future DOT programs and can guide protocols for studies among
      opioid-dependent smokers receiving methadone treatment. TRIAL REGISTRATION:
      clinicaltrials.gov NCT01378858.

PMID- 24928219
TI  - Ionic nature of burn-induced variation potential in wheat leaves.
AB  - Variation potential (VP) in higher plants cells is a transitory depolarization of
      the plasma membrane occurring in response to external damage. The effects of VP
      on different physiological processes are actively studied, but little is known
      about their ionic nature, which limits the interpretation of VP-induced
      functional changes. It is thought that VP generation is based on transient
      inactivation of plasma membrane proton pumps and is not connected to passive
      ionic fluxes. To study burn-induced VP in wheat seedlings, we measured membrane
      electric potential and cell input resistance. Cell input resistance decreased
      during VP generation, indicating that ionic channels were activated. In addition,
      VP amplitude decreased when the extracellular calcium concentration was lowered.
      When anion channels were blocked by ethacrynic acid addition, the VP had poor
      depolarization speed and amplitude. A decrease in the chlorine gradient by
      extracellular chlorine concentration shift leads to lowering of the VP amplitude
      and depolarization speed. This result indicates the role of chlorine efflux in
      depolarization phase formation. The VP repolarization is connected to potassium
      ion efflux, that is confirmed by repolarization suppression under addition of the
      potassium channel blocker tetraethylammonium (TEA) and an increase in the
      extracellular potassium concentration. We also showed that the addition of a
      proton pump inhibitor leads to membrane potential depolarization and inhibition
      of VP generation. These results suggest that the VP may be formed not only by
      transient suppression of proton pumps but also by passive ionic fluxes through
      the membrane. 

PMID- 24928220
TI  - Ectopic expression of the human MutT-type Nudix hydrolase, hMTH1, confers
      enhanced tolerance to oxidative stress in arabidopsis.
AB  - Oxidized nucleotides produced by oxidative stress cause DNA mutations and the
      production of abnormal proteins. Thus, mammalian cells have developed multiple
      MutT-type Nudix hydrolases that exhibit pyrophosphohydrolase activity toward
      oxidized nucleotides in the cytosol, mitochondria and nucleus. On the other hand,
      AtNUDX1 is the only MutT-type Nudix hydrolase in the cytosol of Arabidopsis
      plants. To clarify the physiological significance of the defenses against
      oxidatively induced DNA damage in plant organelles, we analyzed the effects of
      the ectopic expression of the human MutT-type Nudix hydrolase, hMTH1, which was
      localized in the cytosol (cyt-hMTH1), chloroplasts (chl-hMTH1) and mitochondria
      (mit-hMTH1) of Arabidopsis cells, on tolerance to oxidative stress. Tolerance to
      oxidative stress caused by heating and paraquat (PQ) treatment was higher in the
      mit-hMTH1 and chl-hMTH1 plants than in the control and cyt-hMTH1 plants. The
      accumulation of H2O2 and the frequency of dead cells were lower in the mit-hMTH1
      and chl-hMTH1 plants under stressful conditions. The poly(ADP-ribosyl)ation (PAR)
      reaction, which regulates repair systems for damaged DNA, was activated in the
      mit-hMTH1 and chl-hMTH1 plants under heat stress and PQ treatment. Furthermore,
      DNA fragmentation, which caused programmed cell death, was clearly suppressed in
      the mit-hMTH1 and chl-hMTH1 plants under heat stress. These results demonstrated
      that the ectopic expression of hMTH1 in the chloroplasts and mitochondria of
      Arabidopsis enhanced oxidative stress tolerance by activating the PAR reaction
      and suppressing programmed cell death. 

PMID- 24928221
TI  - A new mutation of the PCNT gene in a Colombian patient with microcephalic
      osteodysplastic primordial dwarfism type II: a case report.
AB  - INTRODUCTION: Microcephalic osteodysplastic primordial dwarfism is a syndrome
      characterized by the presence of intrauterine growth restriction, post-natal
      growth deficiency and microcephaly. Microcephalic osteodysplastic primordial
      dwarfism type II is the most distinctive syndrome in this group of entities.
      Individuals affected by this disease present at an adult height of less than 100
      cm, a post-pubertal head circumference of 40 cm or less, mild mental retardation,
      an outgoing personality and bone dysplasia. CASE PRESENTATION: We report the
      first case of a five-year-old Colombian boy of mixed race ancestry (mestizo),
      with clinical features of microcephaly, prominent and narrow nose, arched palate,
      amelogenesis imperfecta, short stature, tall and narrow pelvis, disproportionate
      shortening of fore-arms and legs, and mild coxa vara. Analysis of the PCNT gene
      by sequencing showed the presence of a nucleotide change in exon 10, c. 1468C>T,
      evidencing a new mutation not reported in the literature for microcephalic
      osteodysplastic primordial dwarfism. CONCLUSION: The new mutation identified in
      this case could be associated with the severity of the phenotypic expression of
      the disease, resulting in the extreme short stature of the patient. Further
      studies are required to reach an explanation that can justify such findings, and
      it is vital to emphasize the importance of detection and follow-up by the
      epidemiological surveillance groups in birth defects and rare diseases.

PMID- 24928222
TI  - The effects of 3 weeks of rTMS treatment on P200 amplitude in patients with
      depression.
AB  - Previous studies have reported that repetitive transcranial magnetic stimulation
      (rTMS) induces neuronal plasticity in the brain. Although event-related potential
      (ERP) is an exploration tool, the rTMS effects on ERPs in patients with major
      depression have not been fully explored. We demonstrated that rTMS treatment
      induces changes in brain function in patients with medication-resistant major
      depression using the ERP. Eighteen patients with medication-resistant major
      depression (five males and 13 females) participated in this study. The patients
      received rTMS treatment for 3 weeks. All patients completed clinical scales,
      including the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Scale
      (HAM-A), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (SAI,
      TAI), Ruminative Response Scale, Emotion Regulation Questionnaire, and Cognitive
      Emotion Regulation Questionnaire (CERQ), as well as the ERP auditory oddball
      task, at their first visit (baseline) and at the 3-week visit (3-weeks). The HAM
      D, HAM-A, BDI, SAI, and "blaming others" scale of the CERQ decreased
      significantly after rTMS treatment. In ERP auditory oddball task, when FP1, FP2,
      FZ, FCZ, CZ, and PZ channels were analyzed, P200 amplitudes showed a main effect
      for time of measurement and increased after 3 weeks of rTMS treatment.
      Standardized low-resolution brain electromagnetic tomography showed significant
      activation in the left middle frontal gyrus by 3 weeks of rTMS treatment. The
      results suggest that relatively longer rTMS treatment induces changes in brain
      function in patients with medication-resistant major depression, which can be
      identified using ERP. 

PMID- 24928223
TI  - Fast determination of MMN and P3a responses to linguistically and emotionally
      relevant changes in pseudoword stimuli.
AB  - We developed a new multi-feature mismatch negativity (MMN) paradigm with two
      improvements: Firstly, the standard tone, a pseudoword /ta-ta/ was presented with
      equal probability to the nine linguistically relevant deviants, reducing the
      recording time by 45%. Secondly, three rare, emotionally valenced stimuli: happy,
      angry, and sad utterances of the standard pseudoword were included in the
      sequence. MMN signals reflecting the perceptual properties of the sounds were
      observed for all stimuli. In addition, P3a signals were observed for the rare
      emotionally uttered pseudowords. This 28-min paradigm allows a multi-dimensional
      evaluation of central speech-sound representations (MMN), and attention
      allocation (P3a) to emotional information content of speech. We recommend this
      paradigm for studies on subject groups with impairments in language or emotional
      information processing, such as autism spectrum disorders, attention disorders,
      and alexithymia. 

PMID- 24928224
TI  - The effect of low frequency stimulation of the pedunculopontine tegmental nucleus
      on basal ganglia in a rat model of Parkinson's disease.
AB  - The pedunculopontine nucleus (PPN) has recently been introduced as an alternative
      target to the subthalamic nucleus (STN) or globus pallidus internus (GPi) for the
      treatment of advanced Parkinson's disease with severe and medically intractable
      axial symptoms such as gait and postural impairment. However, it is little known
      about how electrical stimulation of the PPN affects control of neuronal
      activities between the PPN and basal ganglia. We examined how low frequency
      stimulation of the pedunculopontine tegmental nucleus (PPTg) affects control of
      neuronal activities between the PPN and basal ganglia in 6-OHDA lesioned rats. In
      order to identify the effect of low frequency stimulation on the PPTg, neuronal
      activity in both the STN and substantia nigra par reticulata (SNr) were recorded
      and subjected to quantitative analysis, including analysis of firing rates and
      firing patterns. In this study, we found that the firing rates of the STN and SNr
      were suppressed during low frequency stimulation of the PPTg. However, the firing
      pattern, in contrast to the firing rate, did not exhibit significant changes in
      either the STN or SNr of 6-OHDA lesioned rats during low frequency stimulation of
      the PPTg. In addition, we also found that the firing rate of STN and SNr neurons
      displaying burst and random pattern were decreased by low frequency stimulation
      of PPTg, while the neurons displaying regular pattern were not affected. These
      results indicate that low frequency stimulation of the PPTg affects neuronal
      activity in both the STN and SNr, and may represent electrophysiological efficacy
      of low frequency PPN stimulation. 

PMID- 24928225
TI  - Neuroglobin increases brain fitness: Commentary to: "Neuroglobin overexpression
      improves sensorimotor outcomes in a mouse model of traumatic brain injury".

PMID- 24928226
TI  - Resting Energy Expenditure in Critically Ill Patients With Spontaneous
      Intracranial Hemorrhage.
AB  - BACKGROUND: Data on energy requirements of patients with spontaneous intracranial
      hemorrhage (SICH) are scarce. The objective of this study was to determine the
      resting energy expenditure (REE) in critically ill patients with SICH and to
      compare it with the predicted basal metabolic rate (BMR). METHODS: In 30
      nonseptic patients with SICH, the REE was measured during the 10 first
      posthemorrhage days with the use of indirect calorimetry (IC). Predicted BMR was
      also evaluated by the Harris-Benedict (HB) equation. Bland-Altman analysis was
      used to evaluate the agreement between measured and predicted values. The
      possible effect of confounding factors (demographics, disease, and severity of
      illness score) on the evolution of continuous variables was also tested. RESULTS:
      mean predicted BMR, calculated by the HB equation, was 1580.3 +/- 262 kcal/d,
      while measured REE was 1878.9 +/- 478 kcal/d (117.5% BMR). Compared with BMR,
      measured REE values showed a statistically significant increase at all studied
      points (P < .005). Measured and predicted values showed a good correlation (r =
      0.73, P < .001), but the test of agreement between the 2 methods with the Bland
      Altman analysis showed a mean bias (294.6 +/- 265.6 kcal/d) and limits of
      agreement (-226 to 815.29 kcal/d) that were beyond the clinically acceptable
      range. REE values presented a trend toward increase over time (P = .077),
      reaching significance (P < .005) after the seventh day. Significant correlation
      was found between REE and temperature (P = .002, r = 0.63), as well as between
      REE and cortisol level (P = .017, r = 0.62) on the 10th day. No correlation was
      identified between REE and depth of sedation, as well as Acute Physiology and
      Chronic Health Evaluation II, Glasgow Coma Scale, and Hunt and Hess scores.
      CONCLUSIONS: During the early posthemorrhagic stage, energy requirements of
      critically ill patients with SICH are increased, presenting a trend toward
      increase over time. Compared with IC, the HB equation underestimates energy
      requirements and is inefficient in detecting individual variability of REE in
      this group of patients.

PMID- 24928227
TI  - Antioxidant capacity of Ugni molinae fruit extract on human erythrocytes: an in
      vitro study.
AB  - Ugni molinae is an important source of molecules with strong antioxidant activity
      widely used as a medicinal plant in Southern Chile-Argentina. Total phenol
      concentration from its fruit extract was 10.64 +/- 0.04 mM gallic acid
      equivalents. Analysis by means of HPLC/MS indicated the presence of the
      anthocyanins cyanidin and peonidin, and the flavonol quercitin, all in
      glycosylated forms. Its antioxidant properties were assessed in human
      erythrocytes in vitro exposed to HClO oxidative stress. Scanning electron
      microscopy showed that HClO induced an alteration in erythrocytes from a normal
      shape to echinocytes; however, this change was highly attenuated in samples
      containing U. molinae extracts. It also had a tendency in order to reduce the
      hemolytic effect of HClO. In addition, X-ray diffraction experiments were
      performed in dimyristoylphosphatidylcholine (DMPC) and
      dimyristoylphosphatidylethanolamine bilayers, classes of lipids preferentially
      located in the outer and inner monolayers, respectively, of the human erythrocyte
      membrane. It was observed that U. molinae only interacted with DMPC. Results by
      fluorescence spectroscopy on DMPC large unilamellar vesicles and isolated
      unsealed human erythrocyte membranes also showed that it interacted with the
      erythrocyte membrane and DMPC. It is possible that the location of U. molinae
      components into the membrane outer monolayer might hinder the diffusion of HClO
      and of free radicals into cell membranes and the consequent decrease of the
      kinetics of free radical reactions.

PMID- 24928229
TI  - An initial experience with 85 consecutive robotic-assisted rectal dissections:
      improved operating times and lower costs with experience.
AB  - BACKGROUND: Data are limited about the robotic platform in rectal dissections,
      and its use may be perceived as prohibitively expensive or difficult to learn. We
      report our experience with the initial robotic-assisted rectal dissections
      performed by a single surgeon, assessing learning curve and cost. METHODS:
      Following IRB approval, a retrospective chart review was conducted of the first
      85 robotic-assisted rectal dissections performed by a single surgeon between
      9/1/2010 and 12/31/2012. Patient demographic, clinicopathologic, procedure, and
      outcome data were gathered. Cost data were obtained from the University
      HealthSystem Consortium (UHC) database. The first 43 cases (Time 1) were compared
      to the next 42 cases (Time 2) using multivariate linear and logistic regression
      models. RESULTS: Indications for surgery were cancer for 51 patients (60 %),
      inflammatory bowel disease for 18 (21 %), and rectal prolapse for 16 (19 %). The
      most common procedures were low anterior resection (n = 25, 29 %) and
      abdominoperineal resection (n = 21, 25 %). The patient body mass index (BMI) was
      statistically different between the two patient groups (Time 1, 26.1 kg/m(2) vs.
      Time 2, 29.4 kg/m(2), p = 0.02). Complication and conversion rates did not differ
      between the groups. Mean operating time was significantly shorter for Time 2 (267
      min vs. 224 min, p = 0.049) and remained significant in multivariate analysis.
      Though not reaching statistical significance, the mean observed direct hospital
      cost decreased ($17,349 for Time 1 vs. $13,680 for Time 2, p = 0.2). The
      observed/expected cost ratio significantly decreased (1.47 for Time 1 vs. 1.05
      for Time 2, p = 0.007) but did not remain statistically significant in
      multivariate analyses. CONCLUSIONS: Over the series, we demonstrated a
      significant improvement in operating times. Though not statistically significant,
      direct hospital costs trended down over time. Studies of larger patient groups
      are needed to confirm these findings and to correlate them with procedure volume
      to better define the learning curve process.

PMID- 24928228
TI  - Upregulation of excitatory amino acid transporters by coexpression of Janus
      kinase 3.
AB  - Janus kinase 3 (JAK3) contributes to cytokine receptor signaling, confers cell
      survival and stimulates cell proliferation. The gain of function mutation
      JAK3(A572V) is found in acute megakaryoplastic leukemia. Replacement of ATP
      coordinating lysine by alanine yields inactive JAK3(K855A). Most recent
      observations revealed the capacity of JAK3 to regulate ion transport. This study
      thus explored whether JAK3 regulates glutamate transporters EAAT1-4, carriers
      accomplishing transport of glutamate and aspartate in a variety of cells
      including intestinal cells, renal cells, glial cells, and neurons. To this end,
      EAAT1, 2, 3, or 4 were expressed in Xenopus oocytes with or without additional
      expression of mouse wild-type JAK3, constitutively active JAK3(A568V) or inactive
      JAK3(K851A), and electrogenic glutamate transport was determined by dual
      electrode voltage clamp. Moreover, Ussing chamber was employed to determine
      electrogenic glutamate transport in intestine from mice lacking functional JAK3
      (jak3(-/-)) and from corresponding wild-type mice (jak3(+/+)). As a result, in
      EAAT1, 2, 3, or 4 expressing oocytes, but not in oocytes injected with water,
      addition of glutamate to extracellular bath generated an inward current (Ig),
      which was significantly increased following coexpression of JAK3. Ig in oocytes
      expressing EAAT3 was further increased by JAK3(A568V) but not by JAK3(K851A). Ig
      in EAAT3 + JAK3 expressing oocytes was significantly decreased by JAK3 inhibitor
      WHI-P154 (22 uM). Kinetic analysis revealed that JAK3 increased maximal Ig and
      significantly reduced the glutamate concentration required for half maximal Ig
      (Km). Intestinal electrogenic glutamate transport was significantly lower in
      jak3(-/-) than in jak3(+/+) mice. In conclusion, JAK3 is a powerful regulator of
      excitatory amino acid transporter isoforms.

PMID- 24928230
TI  - Endoscopic papillectomy, single-centre experience.
AB  - BACKGROUND: Endoscopic removal of benign tumours of papilla is increasing. Our
      aim was to evaluate the outcome of endoscopic resection of papillary tumours.
      METHODS: In the years 2000-2012, 61 papillectomies were performed in Helsinki
      University Central Hospital. The cases were analysed retrospectively. RESULTS:
      There were 35 patients with benign tumour of papilla without familial adenomatous
      polyposis (FAP), 16 patients with FAP and 10 patients with ampullary cancer.
      Jaundice and bile duct dilation were risk factors for malignancy (p < 0.001). In
      benign tumours, the recurrence rate was 25.5 %. In 5/51 benign tumour cases (9.8
      %), a pancreaticoduodenectomy was performed. The remaining cases were treated
      endoscopically. Neither tumour size, resection in one piece or piecemeal
      technique, nor coagulation of resection margins had an effect on the development
      of residual tumour. The total complication rate was 24.6 %. Pancreatitis
      developed in six patients (9.8 %, 3 mild and 3 moderate). In benign tumour cases,
      pancreatic stent decreased pancreatitis rate (p = 0.045). In cases where only a
      pancreatic sphincterotomy was performed, the risk of pancreatitis was high 4/7
      (57 %). Bleeding was the most common complication (18 %). Only one patient was
      operated due to complication, a post-papillectomy bleeding. In six out of seven
      non-operated cancer patients, the disease progressed. CONCLUSION: Endoscopic
      papillectomy is an effective procedure for treating benign papillary tumours.
      Jaundice and bile duct dilation are more common in malignant tumours. Pancreatic
      stent decreases the risk of post-papillectomy pancreatitis. Pancreatic
      sphincterotomy without stenting carries a high risk of pancreatitis. For
      papillary cancer, surgery is recommended.

PMID- 24928231
TI  - Laparoscopy-assisted versus open colectomy for treatment of colon cancer in the
      elderly: morbidity and mortality outcomes in 545 patients.
AB  - BACKGROUND: Advanced age is a risk factor of major abdominal surgery due to
      diminished functional reserve and increased comorbidity. Laparoscopy-assisted
      colectomy is a well-established procedure in colon cancer surgery. The aim of
      this study was to compare early outcome of elective laparoscopy surgery and open
      colectomy in colon cancer patients according to age. METHODS: A total of 545
      patients with colonic adenocarcinoma underwent elective surgery between 2005 and
      2009. There were 277 patients in the laparoscopic group and 268 in the open.
      Patient characteristics in both groups were homogeneous and further stratified
      into three subgroups by age: <75, between 75-84, and >= 85 years. Main outcome
      measures were early morbidity, mortality, and hospital stay. RESULTS: Open
      surgery group showed a higher overall morbidity rate (37.3 vs. 21.6%, P = 0.001),
      medical complications (16.4 vs. 10.5%, P = 0.033), surgical complications (23.5
      vs. 15.5%, P = 0.034), and mortality (6.7 vs. 3.2%, P = 0.034). The overall
      morbidity rate difference between open and laparoscopy approach disappeared in
      the oldest group (>= 85 years old). Surgical site infections rate was inferior
      for patients <75 years old in laparoscopy group compared with open. Mortality was
      also significantly inferior in laparoscopy group in younger patients (<75 years,
      0 vs. 3%, P = 0.038). Mean hospital stay was shorter for patients in <75 and 75
      84 groups with laparoscopic approach (7.8 vs. 11.4 days and 10 vs. 14.3,
      respectively, P = 0.001) as compared with those who underwent open surgery, but
      these differences disappeared in patients aged >= 85 years. CONCLUSION:
      Laparoscopy-assisted colectomy in patients underwent elective surgical resections
      for colon cancer showed advantages in rate of early complications in patients
      younger than 85 years of age and was found to be as safe and well tolerated as
      open surgery in patients over 85 years of age.

PMID- 24928232
TI  - Comparative assessment of surgeons' task performance and surgical ergonomics
      associated with conventional and modified flank positions: a simulation study.
AB  - BACKGROUND: Flank position is extensively used in retroperitoneoscopic urological
      practice. Most surgeons follow the patients' position in open approaches.
      However, surgical ergonomics of the conventional position in the
      retroperitoneoscopic surgery is poor. We introduce a modified position and
      evaluated task performance and surgical ergonomics of both positions with
      simulated surgical tasks. METHODS: Twenty-one novice surgeons were recruited to
      perform four tasks: bead transfer, ring transfer, continuous suturing, and
      cutting a circle. The conventional position was simulated by setting an endo
      surgical simulator parallel to the long axis of a surgical desk. The modified
      position was simulated by rotating the simulator 30 degrees  with respect to the
      long axis of the desk. The outcome measurements include task performance
      measures, kinematic measures for body alignment, surface electromyography,
      relative loading between feet, and subjective ratings of fatigue. RESULTS: We
      observed significant improvements in both task performance and surgical
      ergonomics parameters under the modified position. For all four tasks, subjects
      finished tasks faster with higher accuracy (p < 0.005 or < 0.001). For ergonomics
      part: (1) The angle between the upper body and the head was decreased by 7.4 +/-
      1.7 degrees ; (2) The EMG amplitude collected from shoulders and left lumber was
      significantly lower (p < 0.05); (3) Relative loading between feet was more
      balanced (p < 0.001); (4) Manual-action muscles and postural muscles are rated
      less fatiguing according to the questionnaire (p < 0.05). CONCLUSIONS:
      Conventional position of patient in retroperitoneoscopic upper urinary tract
      surgery is associated with poor surgical ergonomics. With a simulated surgery, we
      demonstrated that our modified position could significantly improve task
      performance and surgical ergonomics. Further studies are still warranted to
      validate these benefits for both patients and surgeons.

PMID- 24928233
TI  - Ergonomic analysis of robot-assisted and traditional laparoscopic procedures.
AB  - INTRODUCTION: Many laparoscopic surgeons report musculoskeletal symptoms that are
      thought to be related to the ergonomic stress of performing laparoscopy. Robotic
      surgical systems may address many of these limitations. To date, however, there
      have been no studies exploring the quantitative ergonomics of robotic surgery. In
      this study, we sought to compare the activation of bilateral biceps, triceps,
      deltoid, and trapezius muscle groups during traditional laparoscopic surgery
      (TLS) and robot-assisted laparoscopic surgery (RALS) procedures, as quantified by
      surface electromyography (sEMG). METHODS: One surgeon with expertise in TLS and
      RALS performed 18 operative procedures (13 TLS, 5 RALS) while sEMG measurements
      were obtained from bilateral biceps, triceps, deltoid, and trapezius muscles.
      sEMG measurements were normalized to the maximum voluntary contraction of each
      muscle (%MVC). We compared mean %MVC values for each muscle group during TLS and
      RALS with unpaired t-tests and considered differences with a p value <0.05 to be
      statistically significant. RESULTS: Muscle activation was higher during TLS
      compared to RALS in bilateral biceps (L Biceps RALS:1.01%MVC, L Biceps TLS:3.14,
      p = 0.01; R Biceps RALS:1.81%MVC, R Biceps TLS:4.53, p = 0.0002). Muscle
      activation was higher during TLS compared to RALS in bilateral triceps (L Triceps
      RALS:1.73%MVC, L Triceps TLS:3.58, p = 0.04; R Triceps RALS:1.59%MVC, R Triceps
      TLS:5.11, p = 0.02). Muscle activation was higher during TLS compared to RALS in
      bilateral deltoids (L Deltoid RALS:1.50%MVC, L Deltoid TLS:3.68, p = 0.03; R
      Deltoid RALS:1.19%MVC, R Deltoid TLS:2.57, p = 0.01). Significant differences
      were not detected in the bilateral trapezius muscles (L Trapezius RALS:1.50 %MVC,
      L Trapezius TLS:3.68, p = 0.03; R Trapezius RALS:1.19%MVC, R Trapezius TLS:2.57,
      p = 0.01). DISCUSSION: We have quantitatively examined the ergonomics of TLS and
      RALS and shown that in a single surgeon, TLS procedures are associated with
      significantly elevated biceps, triceps, and deltoid activation bilaterally when
      compared to RALS procedures.

PMID- 24928234
TI  - How do risk factors for mortality and overall complication rates following
      laparoscopic and open colectomy differ between inpatient and post-discharge
      phases of care? A retrospective cohort study from NSQIP.
AB  - BACKGROUND: Risk factors for complications differ between laparoscopic (LC) and
      open colectomy (OC) patients, given the selection bias between these groups. How
      risk factors for these outcomes differ between inpatient and post-discharge
      phases of care requires further study. METHODS: A retrospective cohort study
      (2005-2010) using NSQIP data was performed comparing OC and LC patients.
      Multivariable logistic regression was used to compare covariates associated with
      mortality and overall complication rates both before and after hospital
      discharge. RESULTS: Patients in the LC cohort were younger (64.2 vs. 62.5 years;
      P < 0.0001) with a lower incidence of comorbidities. OC was associated with a
      higher incidence of mortality compared to LC among inpatients (3.3 vs. 0.61%, P <
      0.0001) and following discharge (0.88 vs. 0.29%, P < 0.0001). OC also
      demonstrated a higher incidence of overall complication rates for both inpatients
      (22.32 vs. 9.36%, P < 0.0001) and following discharge (8.83 vs. 7.24%, P <
      0.0001). Risk factors (P < 0.05) for mortality following LC included age and
      emergency procedures for inpatients; pre-operative SIRS was associated with
      mortality occurring after discharge. For the OC cohort, risk for mortality was
      increased with smoking and contaminated/dirty wounds for inpatients; pre
      operative weight loss was associated with death following discharge. Factors
      associated with increased risk of morbidity following LC included smoking history
      for inpatients and pre-operative steroid therapy following discharge. Following
      OC, morbidity was strongly associated with ASA scores for inpatients; pre
      operative steroid therapy was a risk factor following discharge. Obesity was
      strongly associated with non-mortal complications in both cohorts following
      discharge. CONCLUSIONS: (1) LC is associated with a lower incidence of post
      operative mortality and complications. (2) Risk factors associated with adverse
      post-operative outcomes change during the post-operative period; surveillance for
      these outcomes should be tailored by operative technique and phase of post
      operative care (3) Obesity is an underappreciated risk for complications
      following discharge for both LC and OC.

PMID- 24928235
TI  - Accuracy of preoperative automatic measurement of the liver volume by CT-scan
      combined to a 3D virtual surgical planning software (3DVSP).
AB  - BACKGROUND: Liver volumetry is a critical component of safe hepatic surgery, in
      order to minimize the risk of postoperative liver failure. Liver volumes can be
      calculated routinely using the time-consuming gold standard method of manual
      volumetry. The current work sought to evaluate an alternative automatic technique
      based on a novel 3D virtual planning software, and to compare it to the manual
      technique. METHODS: A prospective study of patients undergoing liver resection
      was conducted. Every patient had a pre and 2-day postoperative CT-scan. For each
      patient, total, remnant and resected volumes were calculated manually and
      automatically. Planes of resection were verified by a hepatobiliary surgeon and
      compared with postoperative volumes. Paired t-tests and correlation coefficients
      were calculated. RESULTS: A major hepatectomy was carried out in 36/43 patients.
      The automatic TLV (1,759 mL) and the manual TLV (1,832 mL) were significantly
      different (p < 0.001), but extremely highly correlated (r = 0.989). The
      percentages of preoperative RLV (manual 58.5%, automatic 58.9%) were similar,
      with an excellent correlation of 0.917. The preoperative RLV were matched with
      the 2-day postoperative RLV showing a significant difference (p = 0.0301). The
      resected volumes using both techniques (871 and 832 mL) were compared with the
      resected specimen volume (670 mL), showing a significant difference (p < 0.001)
      but a high degree of correlation (r = 0.874). CONCLUSION: The 3D virtual surgical
      planning software is accurate and reliable in determining the total liver and
      future remnant liver volumes. This technique demonstrates a good correlation with
      the manual technique. Future work will be required to confirm these findings and
      to evaluate the clinical value of the three-dimensional planning platform.

PMID- 24928236
TI  - Sounding the death knell for microbes?
AB  - Over the past 5 years, several studies showed that ultrasound, which is sound
      with a frequency>20 kHz, is able to kill bacteria by activating molecules termed
      sonosensitizers (SS) to produce reactive oxygen species, which are toxic to
      microbes. It is our opinion that this work opens up the potential for the
      development of a novel form of ultrasound-mediated antimicrobial therapy. Termed
      sonodynamic antimicrobial chemotherapy (SACT), we define this therapy as a regime
      where a SS is selectively delivered to target microbial cells and activated by
      ultrasound to induce the death of those microbial cells. Here, we review recent
      work on SACT, current understanding of its mechanisms, and future prospects for
      SACT as a therapeutically viable antimicrobial regime.

PMID- 24928237
TI  - A novel scale predicting postoperative delirium (POD) in patients undergoing
      cerebrovascular surgery.
AB  - PURPOSE: The purpose of this study was to develop and test a scale for predicting
      POD in patients undergoing cerebrovascular surgery. METHODS: The predictive scale
      for POD was composed of 32 items reflecting the strongest risk factors as
      determined by a literature review. The NEECHAM Confusion Scale determined POD
      onset and severity. RESULTS: Delirium developed in 38 (31.1%) of the 122 patients
      in our sample. Logistic regression revealed the following risk factors:
      dehydration, age, disturbance of consciousness, underlying illness, and anxiety
      or depression. The final scale was weighted by referring to odds ratios. The area
      under the curve was 0.844 (95% CI=0.766-0.921). The possible total score on this
      scale was 20 points. A cutoff score of 11 was set for risk of POD (patients
      scoring over 12 were considered at higher risk). The median score was 8 (range: 4
      9) in the non-delirium group and 13 (range: 9-16) in the delirium group (U=499.0;
      df=120; p<0.001). Scale scores were moderately correlated with delirium duration
      (rho=0.532; p<0.001). CONCLUSION: The present scale is a promising a tool for
      predicting POD but needs to be studied further.

PMID- 24928238
TI  - Inhibition of c-Jun N-terminal kinase ameliorates early brain injury after
      subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis
      pathway.
AB  - Nur77 is a potent pro-apoptotic member of the orphan nuclear receptor
      superfamily. Our previous study revealed Nur77-mediated apoptotic also involved
      in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH).
      Previous researches show that c-Jun N-terminal kinase (JNK) positively regulates
      Nur77 nuclear export and apoptosis by phosphorylating Nur77. To determine whether
      activation of JNK is directly associated with Nur77 dependent apoptosis pathway.
      We hypothesized that SP600125, a chemical inhibitor of JNK, may effectively
      ameliorate EBI by inhibiting Nur77 phosphorylation and its transcriptional
      activity. Hence, in this study was designed to explore the neuroprotective
      effects of SP600125 in EBI after SAH. Adult male SD rats were randomly assigned
      to four groups: control; SAH + DMSO; SAH + SP10 and SAH + SP30, a dose of 10 and
      30 mg/kg SP600125 was directly administered intraperitoneally 30 min before and 2
      h after SAH induction. SP600125 markedly decreased expressions of p-JNK, p-Nur77,
      Bcl-2, cyto C, caspase-3 and inhibited apoptosis. Improvement of neurological
      deficit, alleviation of brain edema and amelioration of EBI were obtained after
      treatment of SP600125. Transferase-mediated dUTP nick end labeling-positive cells
      were reduced markedly in brain cortex by SP600125. Our studies indicate JNK plays
      important roles in Nur77 activation. These findings strongly support the
      hypothesis that SP600125 treatment can ameliorate EBI after experimentally
      induced SAH by inhibiting a Nur77-dependent apoptotic pathway. 

PMID- 24928239
TI  - Off-line hyphenation of boronate affinity monolith-based extraction with matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry for
      efficient analysis of glycoproteins/glycopeptides.
AB  - Boronate affinity materials have attracted increasing attentions as sample
      enrichment platforms for glycoproteomic analysis in recent years. However, most
      of the boronate affinity materials that have already employed for proteomic
      analysis are suffering from apparent disadvantages, such as alkaline pH for
      binding, weak affinity, and relatively poor selectivity. Benzoboroxoles are a
      unique class of boronic acids which have showed excellent binding properties for
      the recognition of cis-diol-containing compounds. Recently, a 3-carboxy
      benzoboroxole-functionalized monolithic column had been reported and it had
      exhibited the best selectivity and affinity as well as the lowest binding pH
      among all reported boronate affinity monolithic columns. In this study, an off
      line hyphenation of this boronate affinity monolithic column-based extraction
      with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) was developed and the powerfulness of this hyphenated approach in
      the analysis of glycoproteins and glycopeptides in complex samples was
      investigated. The approach was first applied to the analysis of glycopeptides in
      the tryptic digest of horseradish peroxidase (HRP). Totally 22 glycopeptides were
      identified. To the best of our knowledge, this is the best performance among all
      the boronic acid-functionalized materials. We further employed this approach to
      the analysis of intact proteins in human saliva. Totally 6 intact glycoproteins
      were successfully identified. As comparison, when the samples were analyzed
      without extraction, only a few glycopeptides were identified from the tryptic
      digest of HRP while no glycoproteins were found from the saliva samples.

PMID- 24928240
TI  - Electrochemistry/mass spectrometry as a tool in metabolism studies-a review.
AB  - The combination of electrochemistry (EC) and mass spectrometry (MS) has become a
      more and more frequently used approach in metabolism studies in the last decade.
      This review provides insight into the importance of metabolism studies during the
      drug development process and gives a short overview about the conventionally used
      methods since electrochemistry is often intended to substitute or minimize animal
      based studies. The optimization of the electrochemical conditions is of great
      importance for a successful comparison with in vitro approaches. The type of
      metabolism reactions, which can be simulated by EC, has been extended with new
      cell types and working electrodes. Although the mechanism differs from the enzyme
      catalyzed turnover, electrochemistry can be used to simulate a significant number
      of the respective reactions. An expanded set-up consisting of EC, a
      chromatographic separation and MS allows to distinguish between an electrospray
      ionization (ESI) in-source and an electrochemical oxidation and provides
      information on the polarity of the electrogenerated compounds. A main advantage
      of EC for metabolite generation is the possibility to isolate reactive species
      because of the purely instrumental approach. Especially when a preparative
      electrochemical cell with a larger working electrode surface is used, metabolites
      can be generated in sufficient quantities for their subsequent structure
      elucidation. Besides, the compounds can also be used for selective trapping
      experiments with different cell components such as small peptides, proteins or
      DNA bases. Current and possible future developments and applications of EC are
      presented and discussed as well. 

PMID- 24928241
TI  - Spherical silica particles decorated with graphene oxide nanosheets as a new
      sorbent in inorganic trace analysis.
AB  - Graphene oxide (GO) is a novel material with excellent adsorptive properties.
      However, the very small particles of GO can cause serious problems is solid-phase
      extraction (SPE) such as the high pressure in SPE system and the adsorbent loss
      through pores of frit. These problems can be overcome by covalently binding GO
      nanosheets to a support. In this paper, GO was covalently bonded to spherical
      silica by coupling the amino groups of spherical aminosilica and the carboxyl
      groups of GO (GO@SiO2). The successful immobilization of GO nanosheets on the
      aminosilica was confirmed by scanning electron microscopy and X-ray photoelectron
      spectroscopy. The spherical particle covered by GO with crumpled silk wave-like
      carbon sheets are an ideal sorbent for SPE of metal ions. The wrinkled structure
      of the coating results in large surface area and a high extractive capacity. The
      adsorption bath experiment shows that Cu(II) and Pb(II) can be quantitatively
      adsorbed at pH 5.5 with maximum adsorption capacity of 6.0 and 13.6 mg g(-1),
      respectively. Such features of GO nanosheets as softness and flexibility allow
      achieving excellent contact with analyzed solution in flow-rate conditions. In
      consequence, the metal ions can be quantitatively preconcentrated from high
      volume of aqueous samples with excellent flow-rate. SPE column is very stable and
      several adsorption-elution cycles can be performed without any loss of adsorptive
      properties. The GO@SiO2 was used for analysis of various water samples by flame
      atomic absorption spectrometry with excellent enrichment factors (200-250) and
      detection limits (0.084 and 0.27 ng mL(-1) for Cu(II) and Pb(II), respectively).

PMID- 24928242
TI  - Sensitive and selective cocaine electrochemical detection using disposable
      sensors.
AB  - This paper describes the voltammetric determination of cocaine in presence of
      three different interferences that could be found in street samples using
      disposable sensors. The electrochemical analysis of this alkaloid can be affected
      by the presence of codeine, paracetamol or caffeine, whose oxidation peaks may
      overlap and lead to false positives. This work describes two different solutions
      to this problem. On one hand, the modification of disposable carbon sensors with
      carbon nanotubes allows the voltammetric quantification of cocaine by using
      ordinary least squares regressions in the concentration range from 10 to 155
      MUmol L(-1), with a reproducibility of 5.6% (RSD, n = 7. On the other hand,
      partial least squares regressions are used for the resolution of the overlapped
      voltammetric signals when using screen-printed carbon electrodes without any
      modification. Both procedures have been successfully applied to the evaluation of
      the purity of cocaine street samples.

PMID- 24928243
TI  - Voltammetric detection of ovalbumin using a peptide labeled with an electroactive
      compound.
AB  - For this study, a new method was developed to electrochemically detect ovalbumin
      via its binding with the peptide-1(RNRCKGTDVQAW) in lysozymes. The peptide that
      exists at the C-terminal of a lysozyme was combined with ovalbumin. When an
      electroactive compound was introduced to the N-terminal side of the peptide
      through ethylene gycolbis(sulfosuccinimidyl succinate), the labeled peptide-1
      served as a probe for the detection of ovalbumin. The electrode responses of
      labeled peptide-1 were measured after the labeled peptide-1 and ovalbumin were
      incubated in a 0.1 M phosphate buffer (pH 5.6). As a result, the electrode
      response decreased as the concentration of ovalbumin increased. The detection
      limit of ovalbumin was 2.3 * 10(-11) M as estimated at 3-fold the standard
      deviation (3sigma) (n = 5). Because the steric structure of the peptide and some
      of the amino acid residues were related to the binding, we prepared a peptide-2,
      to which the N- and C-terminals of peptide-1 were alternated. The decrease in the
      response for the labeled peptide-2 was less than that for the labeled peptide-1.
      In addition, the peak current of a peptide-3, for which the D of peptide-1 was
      replaced with S, was hardly changed with or without ovalbumin. Therefore, it was
      clear that the binding was influenced by the steric factors and by the sequence
      of the peptide. However, a peptide-1 with bis(sulfosuccinimidyl) suberate was
      designed to investigate the hydrophobic influences on the probe. The change in
      the peak current was smaller than that of peptide-1 with ethylene
      gycolbis(sulfosuccinimidyl succinate), which was due to the hydrophobic
      properties of the alkyl chain between the peptide and the ovalbumin. The proposed
      method could be applied to the determination of ovalbumin in egg whites.
      Consequently, the concept becomes an electrochemical sensing method for proteins
      based on the protein-peptide interaction.

PMID- 24928244
TI  - A pseudo triple-enzyme electrochemical aptasensor based on the amplification of
      Pt-Pd nanowires and hemin/G-quadruplex.
AB  - Our present work aimed at developing a pseudo triple-enzyme cascade
      electrocatalytic electrochemical aptasensor for determination of thrombin with
      the amplification of alcohol dehydrogenase (ADH)-Pt-Pd nanowires bionanocomposite
      and hemin/G-quadruplex structure that simultaneously acted as NADH oxidase and
      HRP-mimicking DNAzyme. With the addition of ethanol to the electrolyte, the ADH
      immobilized on the Pt-Pd nanowires catalyzed ethanol to acetaldehyde accompanied
      by NAD(+) being converted to NADH. Then the hemin/G-quadruplex firstly served as
      NADH oxidase, converting the produced NADH to NAD(+) with the concomitant local
      formation of high concentration of H2O2. Subsequently, the hemin/G-quadruplex
      acted as HRP-mimicking DNAzyme, bioelectrocatalyzing the produced H2O2. At the
      same time, the Pt-Pd nanowires employed in our strategy not only provided a large
      surface area for immobilizing thrombin binding aptamer (TBA) and ADH, but also
      served as HRP-mimicking DNAzyme which rapidly bioelectrocatalyzed the reduction
      of the produced H2O2. Thus, such a pseudo triple-enzyme cascade electrochemical
      aptasensor could greatly promote the electron transfer of hemin and resulted in
      the dramatic enhancement of electrochemical signal. As a result, a wide dynamic
      concentration linear range from 0.2 pM to 20 nM with a low detection limit of
      0.067 pM for thrombin (TB) determination was obtained. The excellent performance
      indicated that our strategy was a promising way for ultrasensitive assays in
      electrochemical aptasensors.

PMID- 24928245
TI  - A luminescence-based probe for sensitive detection of hydrogen peroxide in
      seconds.
AB  - Here, we present a fast and simple hydrogen peroxide assay that is based on time
      resolved fluorescence. The emission intensity of a complex consisting of terbium
      ions (Tb(3+)) and phthalic acid (PA) in HEPES buffer is quenched in the presence
      of H2O2 and this quenching is concentration-dependent. The novel PATb assay
      detects hydrogen peroxide at a pH range from 7.5 to 8.5 and with a detection
      limit of 150 nmol L(-1) at pH 8.5. The total assay time is less than 1 min. The
      linear range of the assay can be adapted by a pH adjustment of the aqueous buffer
      and covers a concentration range from 310 nmol L(-1) to 2.56 mmol L(-1) in total
      which encompasses four orders of magnitude. The assay is compatible with high
      concentrations of all 47 tested inorganic and organic compounds. The PATb assay
      was applied to quantify H2O2 in polluted river water samples. In conclusion, this
      fast and easy-to-use assay detects H2O2 with high sensitivity and precision.

PMID- 24928246
TI  - New procedure of selected biogenic amines determination in wine samples by HPLC.
AB  - A new procedure for determination of biogenic amines (BA): histamine,
      phenethylamine, tyramine and tryptamine, based on the derivatization reaction
      with 2-chloro-1,3-dinitro-5-(trifluoromethyl)-benzene (CNBF), is proposed. The
      amines derivatives with CNBF were isolated and characterized by X-ray
      crystallography and (1)H, (13)C, (19)F NMR spectroscopy in solution. The novelty
      of the procedure is based on the pure and well-characterized products of the
      amines derivatization reaction. The method was applied for the simultaneous
      analysis of the above mentioned biogenic amines in wine samples by the reversed
      phase-high performance liquid chromatography. The procedure revealed correlation
      coefficients (R(2)) between 0.9997 and 0.9999, and linear range: 0.10-9.00 mg L(
      1) (histamine); 0.10-9.36 mg L(-1) (tyramine); 0.09-8.64 mg L(-1) (tryptamine)
      and 0.10-8.64 mg L(-1) (phenethylamine), whereas accuracy was 97%-102% (recovery
      test). Detection limit of biogenic amines in wine samples was 0.02-0.03 mg L(-1),
      whereas quantification limit ranged 0.05-0.10 mg L(-1). The variation
      coefficients for the analyzed amines ranged between 0.49% and 3.92%. Obtained BA
      derivatives enhanced separation the analytes on chromatograms due to the
      inhibition of hydrolysis reaction and the reduction of by-products formation.

PMID- 24928247
TI  - G2-block after irradiation of cells with different p53 status.
AB  - BACKGROUND: Although it is clear that functional p53 is not required for
      radiation-induced G2 block, certain experimental findings suggest a role for p53
      in this context. For instance, as we also confirm here, the maximum accumulation
      in the G2 compartment after X-ray exposure occurs much later in p53 mutants than
      in wild types. It remains to be seen, however, whether this difference is due to
      a longer block in the G2 phase itself. MATERIAL AND METHODS: We observed the
      movement of BrdU-labeled cells through G2 and M into G1. From an analysis of the
      fraction of labeled cells that entered the second posttreatment cell cycle, we
      were able to determine the absolute duration of the G2 and M phases in
      unirradiated and irradiated cells. RESULTS: Our experiments with four cell lines,
      two melanomas and two squamous carcinomas, showed that the radiation-induced
      delay of transition through the G2 and M phases did not correlate with p53
      status. CONCLUSION: We conclude that looking at the accumulation of cells in the
      G2 compartment alone is misleading when differences in the G2 block are
      investigated and that the G2 block itself is indeed independent of functional
      p53.

PMID- 24928248
TI  - FET-PET-based reirradiation and chloroquine in patients with recurrent
      glioblastoma: first tolerability and feasibility results.
AB  - BACKGROUND: Treatment of recurrent glioblastoma (rGBM) remains an unsolved
      clinical problem. Reirradiation (re-RT) can be used to treat some patients with
      rGBM, but as a monotherapy it has only limited efficacy. Chloroquine (CQ) is an
      anti-malaria and immunomodulatory drug that may inhibit autophagy and increase
      the radiosensitivity of GBM. PATIENTS AND METHODS: Between January 2012 and
      August 2013, we treated five patients with histologically confirmed rGBM with re
      RT and 250 mg CQ daily. RESULTS: Treatment was very well tolerated; no CQ-related
      toxicity was observed. At the first follow-up 2 months after finishing re-RT, two
      patients achieved partial response (PR), one patient stable disease (SD), and one
      patient progressive disease (PD). One patient with reirradiated surgical cavity
      did not show any sign of PD. CONCLUSION: In this case series, we observed
      encouraging responses to CQ and re-RT. We plan to conduct a CQ dose escalation
      study combined with re-RT.

PMID- 24928249
TI  - Evaluation of the prognostic role of tumor cell podoplanin expression in locally
      advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND AND PURPOSE: To investigate the potential prognostic role of tumor
      cell podoplanin expression in patients treated with resection followed by
      irradiation or chemoradiotherapy for locally advanced squamous cell carcinoma of
      the head and neck (SCCHN). MATERIALS AND METHODS: Podoplanin expression (<=10 %
      versus > 10 %) and 12 other factors were evaluated in 160 patients for their
      association with locoregional control (LRC), metastases-free (MFS) and overall
      survival (OS). Other factors were age, gender, Eastern Cooperative Oncology Group
      (ECOG) performance status, preradiotherapy (pre-RT) hemoglobin level, tumor site,
      histological grading, T category, N category, American Joint Committee on Cancer
      (AJCC) stage, human papillomavirus (HPV) status, extent of resection and
      concurrent chemotherapy. RESULTS: In multivariate analysis, ECOG performance
      status 0-1 (risk ratio, RR: 3.01; 95 % confidence interval, CI: 1.42-7.14; p =
      0.003), pre-RT hemoglobin levels >= 7.45 mmol/l (12 g/dl; RR: 2.03; 95 % CI: 1.04
      3.94; p = 0.038), oropharyngeal cancer (RR: 1.25; 95 % CI: 1.01-1.55; p = 0.038)
      and T category T1-2 (RR: 1.81; 95 % CI: 1.24-2.79; p = 0.002) were significantly
      associated with improved LRC. T category T1-2 (RR: 1.90; 95 % CI: 1.25-3.06; p =
      0.002) and N category N0-2a (RR: 5.22; 95 % CI: 1.96-18.09; p < 0.001) were
      significantly associated with better MFS. Pre-RT hemoglobin levels >= 7.45 mmol/l
      (RR: 2.44; 95 % CI: 1.27-4.74; p = 0.007), T category T1-2 (RR: 1.97; 95 % CI:
      1.36-3.04; p < 0.001) and N category N0-2a (RR: 2.87; 95 % CI: 1.37-6.61; p =
      0.005) were significantly associated with improved OS. Podoplanin expression <=
      10 % showed a trend towards improved OS on both univariate (p = 0.050) and
      multivariate analysis (RR: 1.86; 95 % CI: 0.96-3.59; p = 0.07). CONCLUSION:
      Treatment outcomes were significantly associated with performance status, pre-RT
      hemoglobin level, tumor site and tumor stage. Tumor cell expression of podoplanin
      <= 10 % showed a trend towards improved OS when compared to podoplanin expression
      of > 10 %.

PMID- 24928250
TI  - Bibliometrics of intraoperative radiotherapy: analysis of technology, practice
      and publication tendencies.
AB  - PURPOSE: To analyze the performance and quality of intraoperative radiation
      therapy (IORT) publications identified in medical databases during a recent
      period in terms of bibliographic metrics. MATERIALS AND METHODS: A bibliometric
      search was conducted for IORT papers published in the PubMed database between
      1997 and 2013. Publication rate was used as a quantity indicator; the 2012
      Science Citation Index Impact Factor as a quality indicator. Furthermore, the
      publications were stratified in terms of study type, scientific topic reported,
      year of publication, tumor type and journal specialty. We performed a one-way
      analysis of variance (ANOVA) to determine differences between the means of the
      analyzed groups. RESULTS: Among the total of 207 journals, articles were reported
      significantly more frequently in surgery (n = 399, 41 %) and radiotherapy
      journals (n = 273, 28 %; p < 0.01). The highest impact factor was achieved by
      clinical oncology journals (p < 0.01). The majority of identified articles were
      retrospective cohort reports (n = 622, 64 %), followed by review articles (n =
      204, 21 %; p < 0.001). Regarding primary topic, reports on cancer outcome
      following specific tumor therapy were most frequently published (n = 661, 68 %; p
      < 0.001) and gained the highest mean impact factor (p < 0.01). Gastrointestinal
      tumor reports were represented most frequently (n = 456, 47 %; p < 0.001) and the
      mean superior impact factor was earned by breast and gynecologic publications (p
      < 0.01). CONCLUSION: We identified a consistent and sustained scientific
      productivity of international IORT expert groups. Most publications appeared in
      journals with surgical and radiooncological content. The highest impact factor
      was achieved by medical oncology journals.

PMID- 24928251
TI  - Treatment options for thyroid eye disease.
AB  - OPINION STATEMENT: Patients with thyroid eye disease (TED) experience hypertrophy
      of their extraocular muscles and an increase in intraorbital fat volume leading
      to eyelid retraction, proptosis, double vision, and optic nerve compression.
      These orbital changes are thought to be due to a cross-reaction of thyroid
      stimulating hormone (TSH) with antigens in the orbit. Therefore, the key to
      treatment is achievement of a euthyroid state in patients with abnormal thyroid
      function. Cigarette smoking is the strongest modifiable risk factor linked with
      progression and poor response to treatment. All TED patients should be counseled
      and offered help with smoking cessation. The treatment of TED symptoms must be
      customized to each patient, as the degree of orbital involvement can vary. During
      the active state, evaluation of sight-threatening compressive optic neuropathy
      and treatment of corneal exposure by an ophthalmologist is crucial to avoid
      irreversible damage. In most patients, local therapy with artificial tears, gels,
      and ointments can offer symptomatic relief of irritation and dryness. In
      addition, antioxidant therapy with selenium has been shown to improve quality of
      life in patients with mild orbital involvement. Some patients will require
      systemic oral or IV steroids at the onset of an active inflammatory state.
      However, approximately one third of patients will not be responsive to steroid
      therapy alone. In these patients, the addition of orbital radiation or use of
      immune modulation has shown value. Orbital decompression surgery should be
      considered for cases of vision-threatening optic neuropathy despite maximal
      medical therapy. Approximately 3-6 months after cessation of the active state and
      stabilization of symptoms, rehabilitative treatment may be offered. Treatment is
      offered in a 3-stage surgical approach with orbital decompression surgery,
      followed by strabismus surgery for any resultant binocular diplopia, and finally
      eyelid surgery to address eyelid retraction. Meanwhile, symptomatic diplopia may
      be addressed with monocular patching or prisms.

PMID- 24928252
TI  - An investigation of preschool teachers' recognition of possible child abuse and
      neglect in Izmir, Turkey.
AB  - Child abuse and neglect have a potentially deleterious impact on children's
      physical, social, and psychological development. Preschool teachers may play a
      crucial role in the protection, early detection, and the intervention of child
      abuse and neglect, as they have the opportunity to establish a close contact with
      the families and to observe day-to-day changes in pupils' behavior. The main
      purpose of this study is to investigate preschool teachers' experiences and
      characteristics in relation to their awareness of possible child abuse and
      neglect signs. A questionnaire survey was designed and administered to 197
      preschool teachers who work for the public preschools in the Izmir province of
      Turkey. In addition to the questionnaire items, a 34-item Likert-type scale
      measuring the level of familiarity with possible signs of child abuse and neglect
      was developed. This scale had an internal consistency of 0.94. The results
      revealed that 10.65% of preschool teachers had training regarding violence
      against children and 2.03% of them had training in child abuse and neglect.
      Overall, 35% of all teachers reported that they had prior experience with pupils
      who were exposed to child abuse and neglect. Moreover, statistical analyses
      indicated that being a parent and having training in child abuse and neglect,
      having experience with maltreated children, and having higher job status were
      significant factors in preschool teachers' ability to recognize the possible
      signs of child abuse and neglect. Our results support that teacher training in
      child abuse and neglect can play an important role in preschool teachers'
      awareness of the possible signs of child abuse and neglect. 

PMID- 24928253
TI  - The relationship between hegemonic norms of masculinity and men's
      conceptualization of sexually coercive acts by women in South Africa.
AB  - While sexual abuse against women and girls in South Africa has generated much
      deserved attention, the awareness of men's experiences of sexual coercion is
      limited, and often restricted to a homosexual context. This article illuminates
      men's experiences of pressurized sex in a heterosexual context, which were
      revealed in a broader men's sexual health study. Fifty sexual history narrative
      interviews were conducted with men purposively sampled from three age categories:
      (18-24, 25-54, and 55+), a wide range of cultural and racial backgrounds, and in
      urban and rural sites across five provinces in South Africa. Narrative interviews
      began with accounts of early knowledge of sex and sexual experimentation and
      explored the range of sexual relationships and experiences through adulthood. The
      narratives privileged the diversity of men's conceptualizations of and the impact
      of reportedly sexually coercive experiences by women. Many men described feeling
      unready for their first sexual experiences but pressured to do so by their peers
      and female partners, who were often older. There were also some instances of
      sexual coercion by women against men, some of which would constitute a criminal
      offense in South Africa. Due to the pressure for men to always be responsive to
      women's sexual desires, these experiences were often not framed as sexual
      coercion. Nevertheless, for many of these men, such experiences were
      uncomfortable and unrewarding. Men's negative responses to such experiences
      appeared to be linked to the fact that they did not fit social stereotypes of
      masculine sexuality as being initiative and dominant. Such coercive experiences
      could influence men's sexual risk-taking, including their use of sexual coercion
      against women. Research on sexual abuse should not be limited to male against
      male sexual abuse, but needs to explore the meanings and experiences associated
      with reported coercion against men by women to more comprehensively prevent and
      respond to sexual violence. 

PMID- 24928254
TI  - School bullying, low self-control, and opportunity.
AB  - The theory of low self-control has been shown to be a valid predictor of a wide
      variety of criminal and deviant behaviors. However, a limited number of studies
      were conducted to understand the relationship between low self-control and
      bullying and the effects of opportunity factors (i.e., parental supervision,
      association with other bullies, negative school environment, and disciplinary
      measures used by teachers) on bullying in the context of low self-control theory.
      The present study, using a sample of nearly 300 youths, examined the effects of
      low self-control and opportunity factors on various types of bullying behaviors.
      Results indicated that youths with low self-control were likely to physically and
      psychologically bully, consistent with the theory's prediction. When opportunity
      measures were introduced, they were stronger explanations of bullying than low
      self-control, especially association with other bullies and youth who experienced
      disciplinary measures by their teacher. Negative school environment was a
      significant predictor of psychological bullying but not for physical bullying.
      Theoretical and policy implications are discussed. 

PMID- 24928255
TI  - Cardiovascular function in children who had chronic lung disease of prematurity.
AB  - OBJECTIVES: Although increased pulmonary arterial pressure is common in infancy
      in preterm infants who develop chronic lung disease of prematurity (CLD), it is
      unknown if the increase persists into childhood. We, therefore, assessed if 8-12
      year-old children with documented CLD in infancy had evidence of right
      ventricular dysfunction or pulmonary arterial hypertension at rest or in response
      to acute hypoxia when compared to preterm and term-born controls. METHODS: We
      studied 90 children: 60 born at <=32 weeks of gestation (28 with CLD and 32
      preterm controls), and 30 term-born controls. All had echocardiography including
      myocardial velocity imaging, at rest and while breathing 15% oxygen and 12%
      oxygen for 20 min each. RESULTS: Baseline oxygen saturation, heart rate, blood
      pressure and echocardiographic markers of left and right ventricular function
      were similar in all three groups. While breathing 12% oxygen, the oxygen
      saturation decreased to 81.9% in the CLD group compared to 85.1% (p<0.05) and
      84.7% (p<0.01) in the preterm and term controls, respectively. In response to
      hypoxia, all three groups showed increases in velocity of tricuspid
      regurgitation, end-diastolic velocity of pulmonary regurgitation, and right
      ventricular relaxation time; and decreases in pulmonary arterial acceleration
      time and the ratio of right ventricular acceleration time to ejection time.
      However, there were no differences between groups. CONCLUSIONS: Childhood
      survivors of CLD have comparable left and right ventricular function at 8-12
      years of age to preterm and term-born children, and no evidence of increased
      pulmonary arterial pressure even after hypoxic exposure.

PMID- 24928256
TI  - Involved-node proton therapy in combined modality therapy for Hodgkin lymphoma:
      results of a phase 2 study.
AB  - PURPOSE: This study describes the early clinical outcomes of a prospective phase
      2 study of consolidative involved-node proton therapy (INPT) as a component of
      combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with
      mediastinal involvement. METHODS AND MATERIALS: Between September 2009 and June
      2013, 15 patients with newly diagnosed HL received INPT after completing
      chemotherapy in an institutional review board-approved protocol comparing the
      dosimetric impact of PT with those of three-dimensional conformal radiation
      therapy (3DCRT) and intensity modulated RT. Based on (18)F-Fluorodeoxyglucose
      positron emission tomography/computed tomography ((18)F-FDG PET/CT) response, 5
      children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4
      cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone,
      Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone
      chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles
      of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely
      evaluated for toxicity during and after treatment, using Common Terminology
      Criteria for Adverse Events, version 3.0, and for relapse by physical examination
      and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS)
      rates were calculated using the Kaplan-Meier method from the time of diagnosis.
      RESULTS: The median follow-up was 37 months (range, 26-55). Two events occurred
      during follow-up: 1 relapse (inside and outside the targeted field) and 1
      transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS
      rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3
      nonhematologic toxicities were observed. CONCLUSIONS: Although decades of follow
      up will be needed to realize the likely benefit of PT in reducing the risk of
      radiation-induced late effects, PT following chemotherapy in patients with HL is
      well-tolerated, and disease outcomes were similar to those of conventional photon
      therapy.

PMID- 24928257
TI  - Late consequential surgical bed soft tissue necrosis in advanced oropharyngeal
      squamous cell carcinomas treated with transoral robotic surgery and postoperative
      radiation therapy.
AB  - PURPOSE: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC)
      managed with transoral robotic surgery (TORS) and postoperative radiation therapy
      (PORT) developed soft tissue necrosis (STN) in the surgical bed months after
      completion of PORT. We investigated the frequency and risk factors. MATERIALS AND
      METHODS: This retrospective analysis included 170 consecutive OP-SCC patients
      treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up.
      STN was defined as ulceration of the surgical bed >6 weeks after completion of
      PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. RESULTS: A total
      of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more
      susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of
      66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0
      5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation
      dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy,
      respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median
      time to STN was 2.5 months after PORT. All patients had resolution of STN after a
      median of 3.7 months. Multivariate analysis identified tonsillar primary (odds
      ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation
      dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis
      (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing
      aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8%
      (2 of 26 patients) experienced STN (all grade 2). CONCLUSIONS: A subset of OP-SCC
      patients treated with TORS and PORT are at risk for developing late consequential
      surgical bed STN. Risk factors include tonsillar location, depth of resection,
      radiation dose to the surgical bed, and severe mucositis. STN risk is
      significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day
      to the surgical bed.

PMID- 24928258
TI  - Effect of inoculation method on the determination of decontamination efficacy
      against Bacillus spores.
AB  - Decontamination studies investigating the effectiveness of products and processes
      for the inactivation of Bacillus species spores have traditionally utilized
      metering viable spores in a liquid suspension onto test materials (coupons). The
      current study addresses the representativeness of studies using this type of
      inoculation method compared to when coupons are dosed with a metered amount of
      aerosolized spores. The understanding of this comparability is important in order
      to assess the representativeness of such laboratory-based testing when deciding
      upon decontamination options for use against Bacillus anthracis spores. Temporal
      inactivation of B. anthracis surrogate (B. subtilis) spores on representative
      materials using fumigation with chlorine dioxide, spraying of a pH-adjusted
      bleach solution, or immersion in the solution was investigated as a function of
      inoculation method (liquid suspension or aerosol dosing). Results indicated that
      effectiveness, measured as log reduction, was statistically significantly lower
      when liquid inoculation was used for some material and decontaminant
      combinations. Differences were mostly noted for the materials observed to be more
      difficult to decontaminate (i.e., wood and carpet). Significant differences in
      measured effectiveness were also noted to be a function of the pH-adjusted bleach
      application method used in the testing (spray or immersion). Based upon this work
      and the cited literature, it is clear that inoculation method, decontaminant
      application method, and handling of non-detects (i.e., or detection limits) can
      have an impact on the sporicidal efficacy measurements.

PMID- 24928259
TI  - Optimization of submerged fermentation conditions for immunosuppressant
      mycophenolic acid production by Penicillium roqueforti isolated from blue-molded
      cheeses: enhanced production by ultraviolet and gamma irradiation.
AB  - Mycophenolic acid (MPA) is a promising drug owing to its immunosuppressive and
      biological activities. In this study, two strains of Penicillium roqueforti
      designated as AG101 and LG109 were selected among several strains isolated from
      Roquefort cheese samples on the basis of their activity for MPA-producing
      ability. The appropriate fermentation conditions necessary for MPA biosynthesis
      by the two respective fungal strains were investigated. These conditions included
      selection of the cultivation medium, agitation rate, incubation temperature,
      fermentation time, pH value, inoculum size, and fermentation medium volume.
      Maximum MPA productivities were maintained when the fermentation process was
      carried out using a medium composed of (g l(-1)): Sucrose, 30; peptone, 5.0;
      KH2PO4, 1.0; MgSO4.7H2O, 0.5 and KCl, 0.5; pH 6.0, inoculated with an inoculum
      size of 6.0 % (v/v), and incubated at 25  degrees C for 10 days at 120 rpm. The
      potentiality of both P. roqueforti strains for further improvement of MPA
      production was applied by mutagenesis through exposure to irradiation by
      ultraviolet rays (UV, 254 nm) for different periods of time and gamma rays at
      various doses (KGy). The dry cell weight of both irradiated fungal strains showed
      a greater reduction when irradiated either with UV or gamma rays. However, the
      MPA yield of both strains was increased by 1.27-1.39 fold when irradiated with UV
      rays and by 2.11-2.33 fold when irradiated with gamma rays, as compared with the
      respective controls (non-irradiated cultures). These findings indicate the future
      possibility to reduce the cost of producing fermentation-based drugs.

PMID- 24928260
TI  - Isolation and identification of an endophytic fungus Pezicula sp. in Forsythia
      viridissima and its secondary metabolites.
AB  - In a survey of endophytic fungal biodiversity, an antimicrobial endophytic
      isolate zjwcf069 was obtained from twigs of Forsythia viridissima, Zhejiang
      Province, Southeast China. Zjwcf069 was then identified as Pezicula sp. through
      combination of morphological and phylogenetic analysis based on ITS-rDNA.
      Zjwcf069 here represented the first endophytic fungus in Pezicula isolated from
      host F. viridissima. From the fermentation broth, four compounds were obtained
      through silica gel column chromatography and Sephadex LH-20 under the guide of
      bioassay. Their structures were elucidated by spectroscopic analysis as mellein
      (1), ramulosin (2), butanedioic acid (3), and 4-methoxy-1(3H)-isobenzofuranone
      (4). Compound 4 here stood for the very first time as natural product from
      microbes. In vitro antifungal assay showed that compound 1 displayed growth
      inhibition against 9 plant pathogenic fungi, especially Botrytis cinerea and
      Fulvia fulva with EC50 values below 50 MUg/mL. Endophytic fungi in medicinal
      plants were good resources for bioactive secondary metabolites.

PMID- 24928261
TI  - Individual differences in field independence influence the ability to determine
      accurate needle angles.
AB  - OBJECTIVE: "Field dependence" is used in cognitive psychology to describe an
      individual's tendency to be visually distracted by the surrounding environment.
      Notwithstanding the role of field dependence in contexts in which spatial
      judgment is important, such as piloting an aircraft, to date, studies linking
      field dependence to surgical skills have been limited. We evaluated whether field
      dependence correlates with an ability to anticipate appropriate needle angles in
      a simulated setting. METHODS: Trainees underwent field dependence testing and
      then participated in a surgical skills exercise. Correlations between field
      dependence and surgical skill were computed. Specifically, cardiothoracic surgery
      residents (n=11) took a battery of cognitive examinations to assess general
      reasoning and visuospatial judgment. Two written tests, the Rod and Frame test
      and the Judgment of Line Orientation test, measured the degree of field
      dependence. The subjects then underwent surgical skills testing. Using a standard
      needle driver, the participants placed curved needles into a cylindrical silicone
      mitral valve model with 10 premarked needle entry and exit sites. The components
      assessed included the ability to load a needle on driver at the appropriate
      angle. RESULTS: The test results showed a parametric distribution, with internal
      cognitive testing controls demonstrating valid testing techniques and methods.
      Performance on the cognitive tests measuring spatial judgment and field
      dependence correlated significantly with skill at determining the appropriate
      needle angle load in an inverse fashion (Judgment of Line Orientation test,
      r=0.61, P<.05; Rod and Frame test, r=-0.52, P=.05), suggesting that residents who
      were not distracted by surrounding objects performed better. Performance on the
      cognitive examinations did not correlate with resident training level.
      CONCLUSIONS: Although our study was of a small cohort, the findings suggest that
      individuals described as field independent (not easily distracted by external
      visual cues) might possess improved ability to determine appropriate needle angle
      loads compared with field-dependent individuals. Additional studies examining the
      role field dependence might play in the acquisition and execution of surgical
      tasks are warranted.

PMID- 24928262
TI  - Increased late mortality after coronary artery bypass surgery complicated by
      isolated new-onset atrial fibrillation: a comprehensive propensity-matched
      analysis.
AB  - OBJECTIVES: The association of new-onset postoperative atrial fibrillation (POAF)
      and late death after coronary artery bypass grafting (CABG) has been confounded
      by the frequent concomitant serious complications that co-occur with POAF. We
      aimed to define the magnitude and time dependence of the effect of isolated POAF
      on late survival after uncomplicated CABG to comprehensively account for
      comorbidity and perioperative confounding factors. METHODS: Nonsalvage CABG
      patients with no history of AF, no concomitant aortic or valvular surgery, and no
      perioperative complications other than POAF were studied (n=6305). Patients were
      divided into AF (n=1211, 68 years old, 72% male) and no-AF (n=5094, 63 years old,
      70% male) groups. Propensity matching was done using 55 patient variables,
      including coronary grafts, completeness of revascularization, and transfusion
      data. The AF effect was quantified using time-segmented hazard ratios by Cox
      regression analysis. RESULTS: Single (1-to-1), double (1-to-2), and triple (1-to
      3) propensity matching of the AF and no-AF was achieved for 1196, 993, and 719
      cases, respectively. The AF group showed significantly worse, yet time-varying, 0
      to 18-year survival: 0 to 1 year, HR, 1.18 (95% confidence interval, 0.77-1.81);
      1 to 6 years, HR, 1.37 (95% confidence interval, 1.12 to 1.67); and 6 to 17
      years, HR, 1.25 (95% confidence interval, 1.05 to 1.49). CONCLUSIONS: Isolated
      POAF was associated with a time-varying increase in mortality after CABG. Given
      these findings and the high incidence of POAF, efforts to reduce POAF should be
      pursued to potentially improve resource usage, morbidity, and mortality.

PMID- 24928263
TI  - Emotional connotations of words related to authority and community.
AB  - We present a database of 858 German words from the semantic fields of authority
      and community, which represent core dimensions of human sociality. The words were
      selected on the basis of co-occurrence profiles of representative keywords for
      these semantic fields. All words were rated along five dimensions, each measured
      by a bipolar semantic-differential scale: Besides the classic dimensions of
      affective meaning (valence, arousal, and potency), we collected ratings of
      authority and community with newly developed scales. The results from cluster,
      correlational, and multiple regression analyses on the rating data suggest a
      robust negativity bias for authority valuation among German raters recruited via
      university mailing lists, whereas community ratings appear to be rather unrelated
      to the well-established affective dimensions. Furthermore, our data involve a
      strong overall negative correlation-rather than the classical U-shaped
      distribution-between valence and arousal for socially relevant concepts. Our
      database provides a valuable resource for research questions at the intersection
      of cognitive neuroscience and social psychology. It can be downloaded as
      supplemental materials with this article. 

PMID- 24928264
TI  - Patient and hospital-level characteristics associated with the use of do-not
      resuscitate orders in patients hospitalized for sepsis.
AB  - BACKGROUND: Identifying factors associated with do-not-resuscitate (DNR) orders
      is an informative step in developing strategies to improve their use. As such, a
      descriptive analysis of the factors associated with the use of DNR orders in the
      early and late phases of hospitalizations for sepsis was performed. METHODS: A
      retrospective cohort of adult patients hospitalized for sepsis was identified
      using a statewide administrative database. DNR orders placed within 24 h of
      hospitalization (early DNR) and after 24 h of hospitalization (late DNR) were the
      primary outcome variables. Multivariable logistic regression analysis was used to
      identify patient, hospital, and healthcare system-related factors associated with
      the use of early and late DNR orders. RESULTS: Among 77,329 patients hospitalized
      for sepsis, 27.5 % had a DNR order during their hospitalization. Among the cases
      with a DNR order, 75.5 % had the order within 24 h of hospitalization. Smaller
      hospital size and the absence of a teaching program increased the likelihood of
      an early DNR order being written. Additionally, greater patient age, female
      gender, White race, more medical comorbidities, Medicare payer status and
      admission from a skilled nursing facility were all significantly associated with
      the likelihood of having an early DNR. The strength of association between these
      factors and the use of late DNR orders was weaker. In contrast, the greater the
      burden of medical comorbidities, the more likely a patient was to receive a late
      DNR order. CONCLUSION: Multiple patient, hospital, and healthcare system-related
      factors are associated with the use of DNR orders in sepsis, many of which appear
      to be independent of a patient's clinical status. Over the course of the
      hospitalization, the burden of medical illness shows a stronger association
      relative to other variables. The influence of these multi-level factors needs to
      be recognized in strategies to improve the use of DNR orders. .

PMID- 24928265
TI  - Capsule commentary on Frank et al., increased hospital and emergency department
      utilization by individuals with recent criminal justice involvement: results of a
      national survey.

PMID- 24928266
TI  - Fluoroquinolone resistant rectal colonization predicts risk of infectious
      complications after transrectal prostate biopsy.
AB  - PURPOSE: Infection after transrectal prostate biopsy has become an increasing
      concern due to fluoroquinolone resistant bacteria. We determined whether
      colonization identified by rectal culture can identify men at high risk for post
      transrectal prostate biopsy infection. MATERIALS AND METHODS: Six institutions
      provided retrospective data through a standardized, web based data entry form on
      patients undergoing transrectal prostate biopsy who had rectal culture performed.
      The primary outcome was any post-transrectal prostate biopsy infection and the
      secondary outcome was hospital admission 30 days after transrectal prostate
      biopsy. We used chi-square and logistic regression statistical analysis. RESULTS:
      A total of 2,673 men underwent rectal culture before transrectal prostate biopsy
      from January 1, 2007 to September 12, 2013. The prevalence of fluoroquinolone
      resistance was 20.5% (549 of 2,673). Fluoroquinolone resistant positive rectal
      cultures were associated with post-biopsy infection (6.6% vs 1.6%, p <0.001) and
      hospitalization (4.4% vs 0.9%, p <0.001). Fluoroquinolone resistant positive
      rectal culture increased the risk of infection (OR 3.98, 95% CI 2.37-6.71, p
      <0.001) and subsequent hospital admission (OR 4.77, 95% CI 2.50-9.10, p <0.001).
      If men only received fluoroquinolone prophylaxis, the infection and
      hospitalization proportion increased to 8.2% (28 of 343) and 6.1% (21 of 343),
      with OR 4.77 (95% CI 2.50-9.10, p <0.001) and 5.67 (95% CI 3.00-10.90, p <0.001),
      respectively. The most common fluoroquinolone resistant bacteria isolates were
      Escherichia coli (83.7%). Limitations include the retrospective study design,
      nonstandardized culture and interpretation of resistance methods. CONCLUSIONS:
      Colonization of fluoroquinolone resistant organisms in the rectum identifies men
      at high risk for infection and subsequent hospitalization from prostate biopsy,
      especially in those with fluoroquinolone prophylaxis only.

PMID- 24928267
TI  - H2O2 generation by bacillus Calmette-Guerin induces the cellular oxidative stress
      response required for bacillus Calmette-Guerin direct effects on urothelial
      carcinoma biology.
AB  - PURPOSE: Exposure of urothelial carcinoma cells to bacillus Calmette-Guerin
      affects cellular redox status and tumor cell biology but the mechanism(s) remain
      unclear. We examined free radical production by bacillus Calmette-Guerin in tumor
      cells in response to the bacillus using global profiling of reactive oxygen
      species/reactive nitrogen species. The relationship between free radical
      generation and downstream cellular events was evaluated. MATERIALS AND METHODS:
      Using fluorescent probes we performed global profiling of reactive oxygen
      species/reactive nitrogen species in heat killed and viable bacillus Calmette
      Guerin, and in the 253J and T24 urothelial carcinoma cell lines after exposure to
      the bacillus. Inhibition of bacillus Calmette-Guerin internalization and H2O2
      pharmacological scavenging were studied for their effect on cellular reactive
      oxygen species/reactive nitrogen species generation and various physiological end
      points. RESULTS: Viable bacillus Calmette-Guerin produced H2O2 and O2(-) but
      nitric oxide was not generated. Loss of viability decreased H2O2 production by
      50% compared to viable bacillus. Bacillus Calmette-Guerin internalization was
      necessary for the bacillus to induce reactive oxygen species/reactive nitrogen
      species generation in urothelial carcinoma cells. Pharmacological H2O2 scavenging
      reversed reactive oxygen species/reactive nitrogen species mediated signaling in
      urothelial carcinoma cells. Bacillus Calmette-Guerin dependent alterations in
      tumor biology, including intracellular signaling, gene expression and
      cytotoxicity, depended on free radical generation. CONCLUSIONS: This study
      demonstrates the importance of free radical generation by bacillus Calmette
      Guerin and intracellular generation of cellular oxidative stress on the
      urothelial carcinoma cell response to the bacillus. Manipulating the cellular
      oxidative stress induced by bacillus Calmette-Guerin represents a potential
      target to increase the efficacy of the bacillus.

PMID- 24928268
TI  - Impact of complications and hospital-free days on health related quality of life
      1 year after radical cystectomy.
AB  - PURPOSE: We determined the extent to which complications as well as number of
      hospital-free days within 30 and 90 days of surgery predicted health related
      quality of life 1 year after radical cystectomy. MATERIALS AND METHODS: We used
      data from a prospective health related quality of life study using a validated
      instrument, the Vanderbilt Cystectomy Index-15. Complications were graded by the
      Clavien system, and hospital length of stay and length of stay during
      readmissions were used to calculate 30 and 90-day hospital-free days,
      respectively. We compared the number of hospital-free days among patients with
      varying levels of complications. Multivariate analysis was performed to determine
      predictors of Vanderbilt Cystectomy Index-15 score 1 year after surgery adjusting
      for demographic (age, gender, comorbidities) and clinical variables (stage and
      diversion type). RESULTS: A total of 100 patients with complete baseline and 1
      year followup health related quality of life data were included in the analysis.
      Median (IQR) 30 and 90-day hospital-free days were 24 (22-25) and 84 (82-85),
      respectively. Patients who experienced any complications had significantly fewer
      30-day hospital-free days (22 vs 24 days, p <0.01) and 90-day hospital-free days
      (81 vs 84 days, p <0.01), and patients with higher grade complications had fewer
      hospital-free days than those with lower grade or no complications (p <0.01). On
      multivariate analysis female gender and baseline Vanderbilt Cystectomy Index-15
      score independently predicted higher 1-year health related quality of life
      scores. CONCLUSIONS: Patients who experience complications after radical
      cystectomy have fewer 30 and 90-day hospital-free days. However, neither predicts
      health related quality of life at 1 year. Instead, long-term health related
      quality of life appears to be driven largely by baseline health related quality
      of life and gender.

PMID- 24928269
TI  - Prospective study of polydimethylsiloxane vs dextranomer/hyaluronic acid
      injection for treatment of vesicoureteral reflux.
AB  - PURPOSE: Endoscopic injection of a bulking agent is becoming a first-line
      treatment for low grade vesicoureteral reflux. We prospectively compared the
      efficacy of 2 such products commercially available in Canada. MATERIALS AND
      METHODS: A total of 275 patients with documented grade I to V vesicoureteral
      reflux were prospectively enrolled in a comparative study between April 2005 and
      February 2011 to be randomly treated endoscopically with either
      polydimethylsiloxane (Macroplastique(r)) or dextranomer/hyaluronic acid copolymer
      (Deflux(r)). Of the ureters 202 were treated with polydimethylsiloxane and 197
      with dextranomer/hyaluronic acid copolymer. Patients were followed with voiding
      cystourethrography at 3 months and renal ultrasonography at 3 months and at 1
      year. Median followup was 4.3 years. The primary outcome was surgical success
      (resolution vs nonresolution), and secondary outcomes included occurrence of
      adverse events. RESULTS: Vesicoureteral reflux was fully corrected in 182 of 202
      ureters (90%) treated with polydimethylsiloxane, compared to 159 of 197 (81%)
      treated with dextranomer/hyaluronic acid copolymer (p <0.05). Obstruction was
      found in 5 ureters. Univariate and multivariate analyses did not allow
      identification of any characteristics that could explain the significant
      difference in the success rates except for the type of product used. CONCLUSIONS:
      We present the largest known prospective evaluation comparing 2 bulking agents
      for the treatment of vesicoureteral reflux. Endoscopic injection of
      polydimethylsiloxane resulted in a better success rate than
      dextranomer/hyaluronic acid copolymer. The rate of resolution obtained with the
      latter is lower than those previously published due to the inclusion of high
      grade reflux.

PMID- 24928270
TI  - Advanced treatment of biologically pretreated coal gasification wastewater by a
      novel integration of heterogeneous catalytic ozonation and biological process.
AB  - Advanced treatment of biologically pretreated coal gasification wastewater (CGW)
      was investigated employing heterogeneous catalytic ozonation integrated with
      anoxic moving bed biofilm reactor (ANMBBR) and biological aerated filter (BAF)
      process. The results indicated that catalytic ozonation with the prepared
      catalyst (i.e. MnOx/SBAC, sewage sludge was converted into sludge based activated
      carbon (SBAC) which loaded manganese oxides) significantly enhanced performance
      of pollutants removal by generated hydroxyl radicals. The effluent of catalytic
      ozonation process was more biodegradable and less toxic than that in ozonation
      alone. Meanwhile, ANMBBR-BAF showed efficient capacity of pollutants removal in
      treatment of the effluent of catalytic ozonation at a shorter reaction time,
      allowing the discharge limits to be met. Therefore, the integrated process with
      efficient, economical and sustainable advantages was suitable for advanced
      treatment of real biologically pretreated CGW. 

PMID- 24928271
TI  - [Implementation of the EndoCert system for certification of arthroplasty centers.
      Experiences from the pilot phase].
AB  - BACKGROUND: EndoCert is an initiative of the Deutschen Gesellschaft fur
      Orthopadie und Orthopadische Chirurgie (DGOOC, German Society for Orthopedics and
      Orthopedic Surgery) which has been available since October 2012 and is the first
      system worldwide for certification of specialized arthroplasty centers. Before
      implementation of this certification concept two sequential pilot phases were
      carried out with representative treatment institutions. The results from these
      pilot clinics are presented with respect to quality improvement effects.
      NONCONFORMITIES: Early effects on the quality of treatment have been achieved by
      rectification of nonconformities determined in the audit with respect to
      structural and process quality. A total of 172 nonconformities found in the 23
      participating pilot clinics could be rectified. Long-term effects on the quality
      of results will in future be analyzed in cooperation with the German
      endoprosthesis register (EPRD) and by accompanying evaluations. FEEDBACK: A close
      feedback of the collated experiences and results to the certification committee,
      which is responsible for the procedure together with the DGOOC, allows continuous
      further development of the system CONCLUSION: EndoCert represents a substantial
      step towards a nationwide safety and improvement of the quality in arthroplasty
      treatment within the preoperative, perioperative and postoperative framework and
      can in future represent a decisive tool together with the EPRD in quality
      management.

PMID- 24928274
TI  - Short-term moderate hypothermia stimulates alkaline phosphatase activity and
      osteocalcin expression in osteoblasts by upregulating Runx2 and osterix in vitro.
AB  - Exposure of Normal Human Osteoblast cells (NHOst) to a period of hypothermia may
      interrupt their cellular functions, lead to changes in bone matrix and disrupt
      the balance between bone formation and resorption, resulting in bone loss or
      delayed fracture healing. To investigate this possibility, we exposed NHOst cells
      to moderate (35  degrees C) and severe (27  degrees C) hypothermia for 1, 12, 24
      and 72 h. The effects of hypothermia with respect to cell cytoskeleton
      organization, metabolic activity and the expression of cold shock chaperone
      proteins, osteoblast transcription factors and functional markers, were examined.
      Our findings showed that prolonged moderate hypothermia retained the
      polymerization of the cytoskeletal components. NHOst cell metabolism was affected
      differently according to hypothermia severity. The osteoblast transcription
      factors Runx2 and osterix were necessary for the transcription and translation of
      bone matrix proteins, where alkaline phosphatase (Alp) activity and osteocalcin
      (OCN) bone protein were over expressed under hypothermic conditions.
      Consequently, bone mineralization was stimulated after exposure to moderate
      hypothermia for 1 week, indicating bone function was not impaired. The cold shock
      chaperone protein Rbm3 was significantly upregulated (p<0.001) during the
      cellular stress adaption under hypothermic conditions. We suggest that Rbm3 has a
      dual function: one as a chaperone protein that stabilizes mRNA transcripts and a
      second one in enhancing the transcription of Alp and Ocn genes. Our studies
      demonstrated that hypothermia permitted the in vitro maturation of NHOst cells
      probably through an osterix-dependent pathway. For that reason, we suggest that
      moderate hypothermia can be clinically applied to counteract heat production at
      the fracture site that delays fracture healing.

PMID- 24928273
TI  - Aim24 stabilizes respiratory chain supercomplexes and is required for efficient
      respiration.
AB  - The mitochondrial respiratory chain is essential for the conversion of energy
      derived from the oxidation of metabolites into the membrane potential, which
      drives the synthesis of ATP. The electron transporting complexes bc1 complex and
      the cytochrome c oxidase assemble into large supercomplexes, allowing efficient
      energy transduction. Currently, we have only limited information about what
      determines the structure of the supercomplex. Here, we characterize Aim24 in
      baker's yeast as a protein, which is integrated in the mitochondrial inner
      membrane and is required for the structural integrity of the supercomplex.
      Deletion of AIM24 strongly affects activity of the respiratory chain and induces
      a growth defect on non-fermentable medium. Our data indicate that Aim24 has a
      function in stabilizing the respiratory chain supercomplexes. 

PMID- 24928272
TI  - Role of IL-17A and IL-10 in the antigen induced inflammation model by Mycoplasma
      pneumoniae.
AB  - BACKGROUND: Mycoplasma pneumoniae is one of the causative organisms of community
      acquired pneumonia which is found commonly in younger patients. Extrapulmonary
      complications similar to autoimmune disease are caused by M. pneumoniae following
      the initial infection. The mechanism and pathology of onset is not clear, but it
      is considered that excessive host immunoreactions play a part in the onset of
      mycoplasmal pneumonia and its extrapulmonary complications. In this study, we
      investigated the participation of the immune response, excluding the
      participation of Th1 and Th2 which has previously been investigated. RESULTS: In
      this study, the host immune response of an antigen induced inflammation model
      using SPF mice repeatedly sensitized with M. pneumoniae antigens was analyzed.
      The specificity of M. pneumoniae antigens in the Th17 response of murine
      lymphocytes in vitro was also examined. Frequent and concentrated sensitization
      induced exacerbation of lung inflammation immunologically and pathologically, and
      evoked intrapulmonary IL-17A and IL-10 production. M. pneumoniae antigen
      stimulation induced proliferation of mouse lymphocytes and caused production of
      IL-17A and IL-10. In addition, it was shown that IL-17A and IL-10 production was
      increased in the presence of IL-6 and TGF-beta1. CONCLUSIONS: It was shown that
      M. pneumoniae antigens induced potent immunoreaction and enhanced the Th17 cell
      response both in vivo and in vitro, and that both Treg and IL-10 are involved in
      the suppression of IL-17A production. This raises the possibility that breakdown
      of the immune balance may be part of the process leading to subsequent
      development of extrapulmonary mycoplasmal pneumonia.

PMID- 24928275
TI  - Genetic link between Cabeza, a Drosophila homologue of Fused in Sarcoma (FUS),
      and the EGFR signaling pathway.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that
      causes progressive muscular weakness. Fused in Sarcoma (FUS) that has been
      identified in familial ALS is an RNA binding protein that is normally localized
      in the nucleus. However, its function in vivo is not fully understood. Drosophila
      has Cabeza (Caz) as a FUS homologue and specific knockdown of Caz in the eye
      imaginal disc and pupal retina using a GMR-GAL4 driver was here found to induce
      an abnormal morphology of the adult compound eyes, a rough eye phenotype. This
      was partially suppressed by expression of the apoptosis inhibitor P35. Knockdown
      of Caz exerted no apparent effect on differentiation of photoreceptor cells.
      However, immunostaining with an antibody to Cut that marks cone cells revealed
      fusion of these and ommatidia of pupal retinae. These results indicate that Caz
      knockdown induces apoptosis and also inhibits differentiation of cone cells,
      resulting in abnormal eye morphology in adults. Mutation in EGFR pathway-related
      genes, such as rhomboid-1, rhomboid-3 and mirror suppressed the rough eye
      phenotype induced by Caz knockdown. Moreover, the rhomboid-1 mutation rescued the
      fusion of cone cells and ommatidia observed in Caz knockdown flies. The results
      suggest that Caz negatively regulates the EGFR signaling pathway required for
      determination of cone cell fate in Drosophila. 

PMID- 24928276
TI  - Molecular cloning, regulation, and functional analysis of two GHS-R genes in
      zebrafish.
AB  - Mammalian ghrelin is derived from stomach and regulates growth hormone release
      and appetite by modulating GHS-R (Growth hormone secretagogue receptor) activity.
      Zebrafish has been developed as a forward genetic screening model system and
      previous screening identified a number of genes involved in multiple signaling
      pathways. In this system, ghrelin has been identified and its function and
      regulation have been shown to be highly conserved to that of mammals. Here, we
      identified three isoforms of zGHS-R1 and one of zGHS-R2 (zGHS-R2a), and
      characterized their expression, regulation and function. Three isoforms of zGHS
      R1, which we named zGHS-R1a, zGHS-R1b, and zGHS-R1c, are generated by alternative
      splicing. The expression of zGHS-R1 is highly enriched in brain, intestine
      tissue, and skin tissues. Compared to zGHS-R1, the expression pattern of zGHS-R2a
      is rather evenly distributed. A 15 day fasting elevated expression of zGHS-R1 and
      zGHS-R2 transcripts in anterior intestine tissues, but not in brain. Whereas zGHS
      R1a, zGHS-R1c, and zGHS-R2a appear to be presented on the plasma membrane, the
      localization of zGHS-R1b seems to be restricted in the intracellular region.
      Treatment of ghrelin agonist, L692,585 or goldfish ghrelin peptides but not rat
      ghrelin, elevated intracellular Ca(2+) level and phosphorylation of ERK in HEK
      293 cells expressing zGHS-R1a, but not zGHS-R1b, zGHS-R1c, or zGHS-R2a. It
      appears that besides core ghrelin peptide sequence of GS/TSF additional amino
      acids are required for the activation of zGHS-R1a, as rat ghrelin induces neither
      intracellular Ca(2+) mobilization nor ERK phosphrylation. These results suggest
      that ghrelin system in zebrafish is highly conserved to that of mammals, and thus
      is an ideal in vivo model for dissecting ghrelin system. 

PMID- 24928277
TI  - Induction of galectin-1 by TGF-beta1 accelerates fibrosis through enhancing
      nuclear retention of Smad2.
AB  - Fibrosis is one of the most serious side effects in cancer patients undergoing
      radio-/ chemo-therapy, especially of the lung, pancreas or kidney. Based on our
      previous finding that galectin-1 (Gal-1) was significantly increased during
      radiation-induced lung fibrosis in areas of pulmonary fibrosis, we herein
      clarified the roles and action mechanisms of Gal-1 during fibrosis. Our results
      revealed that treatment with TGF-beta1 induced the differentiation of fibroblast
      cell lines (NIH3T3 and IMR-90) to myofibroblasts, as evidenced by increased
      expression of the fibrotic markers smooth muscle actin-alpha (alpha-SMA),
      fibronectin, and collagen (Col-1). We also observed marked and time-dependent
      increases in the expression level and nuclear accumulation of Gal-1. The TGF
      beta1-induced increases in Gal-1, alpha-SMA and Col-1 were decreased by
      inhibitors of PI3-kinase and p38 MAPK, but not ERK. Gal-1 knockdown using shRNA
      decreased the phosphorylation and nuclear retention of Smad2, preventing the
      differentiation of fibroblasts. Gal-1 interacted with Smad2 and phosphorylated
      Smad2, which may accelerate fibrotic processes. In addition, up-regulation of Gal
      1 expression was demonstrated in a bleomycin (BLM)-induced mouse model of lung
      fibrosis in vivo. Together, our results indicate that Gal-1 may promote the TGF
      beta1-induced differentiation of fibroblasts by sustaining nuclear localization
      of Smad2, and could be a potential target for the treatment of pulmonary fibrotic
      diseases. 

PMID- 24928278
TI  - Understanding conduct disorder: The ways in which mothers attempt to make sense
      of their children's behaviour.
AB  - 'Disruptive behaviour disorders' are the most common reason for referral to Child
      and Adolescent Mental Health Services (CAMHS). Current treatment guidelines focus
      on parent-training programmes. Difficulties are often reported when engaging
      families, with parental attributions and attitudes towards help-seeking proposed
      as influential factors. Previous research has tended to privilege pre-existing
      frameworks; this study utilised qualitative methods to add to the current
      understanding of the ways in which parents make sense of their children's
      behaviour. Semi-structured interviews were carried out with six mothers,
      recruited through CAMHS. Interpretative Phenomenological Analysis (IPA) revealed
      four master themes: 'Understanding the Emotional Child', 'The Emotional Parent',
      'Getting Help' and 'The Journey'. Participants used a variety of explanations in
      order to make sense of their children's behaviour, including the impact of loss
      and trauma. Help-seeking was associated with feelings of shame, and services were
      often viewed as inconsistent and stigmatising. In contrast, positive experiences
      were those which were characterised as being non-judgemental, normalising and
      took into account the wider family context, including mothers' own emotional
      needs. These findings were discussed in relation to existing research and
      implications for clinical practice. 

PMID- 24928279
TI  - Psychometric properties of the Turkish version of the child PTSD symptom scale.
AB  - OBJECTIVE: Psychometric properties of the Turkish version of the Child PTSD
      Symptom Scale (CPSS) were examined in a sample of young individuals who
      experienced a severe earthquake. METHOD: Subjects were 479 children and
      adolescents recruited from schools after 18 months of Van earthquake. Mean age
      was 12.83 (SD+/-1.88), ranging from 8 to 18. RESULTS: Psychometric features were
      generally good for the CPSS. The original three-factor structure was replicated
      in this study. Internal consistency of the scale was good (ranged from alpha=.70
      to alpha=.89 for total and subscale scores). The CPSS demonstrated good
      convergent validity with Child Post-Traumatic Stress Disorder Reaction Index
      scores as well as good divergent validity with the State and Trait Anxiety
      Inventory for Children and Child Depression Inventory. As an evidence for a good
      discriminant validity, the CPSS successfully distinguished high PTSD individuals
      from low PTSD individuals. CONCLUSION: The CPSS had sound psychometric properties
      in a Turkish youth population.

PMID- 24928280
TI  - Diagnostic performance of dual-energy contrast-enhanced subtracted mammography in
      dense breasts compared to mammography alone: interobserver blind-reading
      analysis.
AB  - PURPOSE: To analyse the accuracy of dual-energy contrast-enhanced spectral
      mammography in dense breasts in comparison with contrast-enhanced subtracted
      mammography (CESM) and conventional mammography (Mx). MATERIALS AND METHODS: CESM
      cases of dense breasts with histological proof were evaluated in the present
      study. Four radiologists with varying experience in mammography interpretation
      blindly read Mx first, followed by CESM. The diagnostic profiles, consistency and
      learning curve were analysed statistically. RESULTS: One hundred lesions (28
      benign and 72 breast malignancies) in 89 females were analysed. Use of CESM
      improved the cancer diagnosis by 21.2 % in sensitivity (71.5 % to 92.7 %), by
      16.1 % in specificity (51.8 % to 67.9 %) and by 19.8 % in accuracy (65.9 % to
      85.8 %) compared with Mx. The interobserver diagnostic consistency was markedly
      higher using CESM than using Mx alone (0.6235 vs. 0.3869 using the kappa ratio).
      The probability of a correct prediction was elevated from 80 % to 90 % after 75
      consecutive case readings. CONCLUSION: CESM provided additional information with
      consistent improvement of the cancer diagnosis in dense breasts compared to Mx
      alone. The prediction of the diagnosis could be improved by the interpretation of
      a significant number of cases in the presence of 6 % benign contrast enhancement
      in this study. KEY POINTS: * DE-CESM improves the cancer diagnosis in dense
      breasts compared with mammography. * DE-CESM shows greater consistency than
      mammography alone by interobserver blind reading. * Diagnostic improvement of DE
      CESM is independent of the mammographic reading experience.

PMID- 24928281
TI  - Reengineering Biomedical Translational Research with Engineering Ethics.
AB  - It is widely accepted that translational research practitioners need to acquire
      special skills and knowledge that will enable them to anticipate, analyze, and
      manage a range of ethical issues. While there is a small but growing literature
      that addresses the ethics of translational research, there is a dearth of
      scholarship regarding how this might apply to engineers. In this paper we examine
      engineers as key translators and argue that they are well positioned to ask
      transformative ethical questions. Asking engineers to both broaden and deepen
      their consideration of ethics in their work, however, requires a shift in the way
      ethics is often portrayed and perceived in science and engineering communities.
      Rather than interpreting ethics as a roadblock to the success of translational
      research, we suggest that engineers should be encouraged to ask questions about
      the socio-ethical dimensions of their work. This requires expanding the
      conceptual framework of engineering beyond its traditional focus on "how" and
      "what" questions to also include "why" and "who" questions to facilitate the
      gathering of normative, socially-situated information. Empowering engineers to
      ask "why" and "who" questions should spur the development of technologies and
      practices that contribute to improving health outcomes. 

PMID- 24928282
TI  - Preparedness for a major incident: creation of an epidemiology protocol for a
      health protection register in England.
AB  - Large incidents and natural disasters are on the increase globally. They can have
      a major impact lasting many years or decades; and can affect large groups of
      people including those that are more susceptible to adverse consequences.
      Following a major incident, it may be considered necessary to establish a
      register of those people affected by the incident to provide appropriate advice
      on relevant immediate and longer-term public health interventions that may be
      required, provide reassurance to the public that their care is paramount, to
      reassure the worried well to avoid them inappropriately overwhelming local
      services, and to facilitate epidemiological investigations. Arrangements for the
      prompt follow-up of populations after large incidents or disasters have been
      agreed in England and a protocol for establishing a register of individuals
      potentially affected by a large incident has been developed. It is important for
      countries to have a protocol for implementing a health register if the
      circumstances require one to be in place, and are supported by Public Health
      Authorities. Health registers facilitate the initial descriptive epidemiology of
      exposure and provide the opportunity of carrying out long term analytical studies
      on the affected population. Such epidemiological studies provide a greater
      understanding of the impact that a large incident can have on health, which in
      turn helps in the planning of health care provision. Registers can also assist
      more directly in providing access to individuals in need of physical and mental
      health interventions. The challenge that still remains is to formally pilot the
      register in the field and refine it based on that experience. 

PMID- 24928284
TI  - Effects of omega3 supplementation in elderly patients with acute myocardial
      infarction: design of a prospective randomized placebo controlled study.
AB  - BACKGROUND: Both epidemiological and randomized clinical studies suggest that
      supplementation with very-long-chain marine polyunsaturated n-3 fatty acids (n-3
      PUFA) have cardioprotective effects, however these results are not without
      controversy. Study population, sample-size, type of supplementation and type of
      endpoint have all varied widely accross different studies.Therefore, the aims of
      the present study are to evaluate the effect of 2 years supplementation with
      capsules of very-long chain marine n-3 PUFA on top of standard therapy in elderly
      patients after acute myocardial infarction (AMI).In addition, special
      characteristics of this population with regard to prediction of clinical outcome
      will be investigated. The hypothesis is that this supplementation on top of
      modern therapy will reduce the occurence of major cardiovascular events (MACE).
      We present the design of the OMEMI (OMega-3 fatty acids in Elderly patients with
      Myocardial Infarction) study. METHODS/DESIGN: The OMEMI study is designed as a
      randomized, placebo-controlled double-blind multicenter trial.Included are
      patients >=70-82 years of age who have sustained AMI. Patients of either gender
      are eligible. Sample size calculation based on existing literature has resulted
      in the need for 1400 patients followed for 2 years, based on the assumption that
      the n-3 PUFA supplementation will reduce MACE with 30%. The study medication is
      Pikasol(r) Axellus AS, Norway, 3 capsules (1.8 g eicosapentaenoic acid (EPA) +
      docohexaenoic acid (DHA)) per day, and matching placebo is corn oil. The Primary
      end-point is the composite of total mortality, first non-fatal recurring AMI,
      stroke and revascularization. Secondary end-point is the occurrence of new onset
      atrial fibrillation. Extensive biobanking will be performed, including adipose
      tissue biopsies. Compliance will be assessed by measurements of the fatty acid
      profile in serum, sampled at inclusion, after 12 months and at the end of study.
      DISCUSSION: The OMEMI study is scheduled to terminate when the last included
      patient has been followed for 2 years. To the best of our knowledge, the OMEMI
      study is the first to evaluate the effect of n-3 PUFAs on CVDs and mortality in a
      high risk elderly population having suffered an acute myocardial infarction.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT01841944.

PMID- 24928285
TI  - The two sides of warfare: an extended model of altruistic behavior in ancestral
      human intergroup conflict.
AB  - Building on and partially refining previous theoretical work, this paper presents
      an extended simulation model of ancestral warfare. This model (1) disentangles
      attack and defense, (2) tries to differentiate more strictly between selfish and
      altruistic efforts during war, (3) incorporates risk aversion and deterrence, and
      (4) pays special attention to the role of brutality. Modeling refinements and
      simulation results yield a differentiated picture of possible evolutionary
      dynamics. The main observations are: (a) Altruism in this model is more likely to
      evolve for defenses than for attacks. (b) Risk aversion, deterrence, and the
      interplay of migration levels and brutality can change evolutionary dynamics
      substantially. (c) Unexpectedly, one occasional simulation outcome is a
      dynamically stable state of "tolerated intergroup theft," raising the question as
      to whether corresponding patterns also exist in real intergroup conflicts.
      Finally, possible implications for theories of the coevolution of bellicosity and
      altruism in humans are discussed. 

PMID- 24928286
TI  - Intramuscular midazolam versus intravenous diazepam for treatment of seizures in
      the pediatric emergency department: a randomized clinical trial.
AB  - AIM: To compare the therapeutic efficacy of intramuscular midazolam (MDZ-IM) with
      that of intravenous diazepam (DZP-IV) for seizures in children. DESIGN:
      Randomized clinical trial. SETTING: Pediatric emergency department. PATIENTS:
      Children aged 2 months to 14 years admitted to the study facility with seizures.
      INTERVENTION: Patients were randomized to receive DZP-IV or MDZ-IM. MAIN
      MEASUREMENTS: Groups were compared with respect to time to treatment start (min),
      time from drug administration to seizure cessation (min), time to seizure
      cessation (min), and rate of treatment failure. Treatment was considered
      successful when seizure cessation was achieved within 5min of drug
      administration. RESULTS: Overall, 32 children (16 per group) completed the study.
      Intravenous access could not be obtained within 5min in four patients (25%) in
      the DZP-IV group. Time from admission to active treatment and time to seizure
      cessation was shorter in the MDZ-IM group (2.8 versus 7.4min; p<0.001 and 7.3
      versus 10.6min; p=0.006, respectively). In two children per group (12.5%),
      seizures continued after 10min of treatment, and additional medications were
      required. There were no between-group differences in physiological parameters or
      adverse events (p=0.171); one child (6.3%) developed hypotension in the MDZ-IM
      group and five (31%) developed hyperactivity or vomiting in the DZP-IV group.
      CONCLUSION: Given its efficacy and ease and speed of administration,
      intramuscular midazolam is an excellent option for treatment of childhood
      seizures, enabling earlier treatment and shortening overall seizure duration.
      There were no differences in complications when applying MDZ-IM or DZP-IV.

PMID- 24928287
TI  - Editorial commentary: Trichomonas vaginalis testing and screening in a high-risk
      population: is this a glimpse into the future?

PMID- 24928289
TI  - Editorial commentary: some perspectives regarding risk factors for a(H7N9)
      influenza virus infection in humans.

PMID- 24928290
TI  - Vertical transmission of hepatitis C virus: systematic review and meta-analysis.
AB  - BACKGROUND: We conducted a systematic review of estimates of hepatitis C virus
      (HCV) vertical transmission risk to update current estimates published more than
      a decade ago. METHODS: PubMed and Embase were searched and 109 articles were
      included. Pooled estimates of risk were generated for children born to HCV
      antibody-positive and viremic women, aged >=18 months, separately by maternal
      human immunodeficiency virus (HIV) coinfection. RESULTS: Meta-analysis of the
      risk of vertical HCV infection to children of HCV antibody-positive and RNA
      positive women was 5.8% (95% confidence interval [CI], 4.2%-7.8%) for children of
      HIV-negative women and 10.8% (95% CI, 7.6%-15.2%) for children of HIV-positive
      women. The adjusted meta-regression model explained 51% of the between-study
      variation in the 25 included risk estimates. Maternal HIV coinfection was the
      most important determinant of vertical transmission risk (adjusted odds ratio,
      2.56 [95% CI, 1.50-4.43]). Additional methodological (follow-up rate and
      definition of infection in children) and risk factors independently predicted HCV
      infection and need to be captured and reported by future studies of vertical
      transmission. Studies assessing the contribution of nonvertical exposures in
      early childhood to HCV prevalence among children at risk of vertical transmission
      are needed. CONCLUSIONS: More than 1 in every 20 children delivered by HCV
      chronically infected women are infected, highlighting that vertical transmission
      likely constitutes the primary transmission route among children. These updated
      estimates are a basis for decision making in prioritization of research into risk
      reducing measures, and inform case management in clinical settings, especially
      for HIV-positive women in reproductive age.

PMID- 24928291
TI  - Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients
      with streptococcal toxic shock syndrome: a comparative observational study.
AB  - BACKGROUND: Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis
      are the 2 most severe invasive manifestations caused by group A Streptococcus
      (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive
      treatment with a beneficial effect on mortality. However the clinical evidence is
      limited. Here we aim to further document the clinical efficacy of administered
      IVIG therapy in a comparative observational study of well-defined patients with
      STSS. METHODS: The effect of IVIG was evaluated in patients with STSS
      prospectively identified in a nationwide Swedish surveillance study conducted
      between April 2002 and December 2004. Detailed data on symptoms, severity of
      disease, treatment, and outcome were obtained from 67 patients. Crude and
      adjusted analyses with logistic regression were performed. RESULTS: Twenty-three
      patients received IVIG therapy compared with 44 who did not. No significant
      difference in comorbidities, severity of disease, organ failures, or sex was
      seen, but the IVIG group was slightly younger and had a higher degree of
      necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival.
      Adjusted analysis revealed that factors influencing survival in STSS were
      Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007),
      clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). CONCLUSIONS: This
      comparative observational study of prospectively identified STSS patients
      demonstrates that both IVIG and clindamycin therapy contribute to a significantly
      improved survival in STSS.

PMID- 24928292
TI  - Added benefit of nucleic acid amplification testing for the diagnosis of
      Trichomonas vaginalis among men and women attending a sexually transmitted
      diseases clinic.
AB  - BACKGROUND: Trichomonas vaginalis (TV) is the most common nonviral sexually
      transmitted infection (STI) in the world. However, TV is not a reportable STI
      and, with the exception of HIV-positive women, there are no guidelines for
      screening in women or men. The objective of this study was to determine the added
      value of nucleic acid amplification tests (NAATs) for detection of TV in men and
      women at high risk for infection as well as correlates of infection. METHODS:
      This was a review of clinical and laboratory data of men and women presenting to
      the Jefferson County Department of Health Sexually Transmitted Diseases (STD)
      Clinic and receiving a TV NAAT. RESULTS: During 2012-2013, 6335 patients (3821
      women and 2514 men) received a TV NAAT on endocervical, urethral, or urine
      specimens. Overall TV prevalence was 20.2%; 27.0% in women and 9.8% in men.
      Correlates of TV among men included age >40 years, African American race, and >=5
      polymorphonuclear cells per high-power field on urethral Gram stain. Age >40
      years, African American race, leukorrhea on wet mount, elevated vaginal pH,
      positive whiff test, and concurrent gonococcal infection were positively
      associated with TV among women. TV NAAT detected approximately one-third more
      infections among women than wet mount alone. CONCLUSIONS: TV prevalence among men
      and women was high in this study, suggesting that both groups should be routinely
      screened, including those aged >40 years. Improved detection of TV by routine
      implementation of NAATs should result in better control of this common, treatable
      STI.

PMID- 24928293
TI  - Risk factors for influenza A(H7N9) disease--China, 2013.
AB  - BACKGROUND: The majority of human cases of novel avian influenza A(H7N9), which
      emerged in China in spring 2013, include reported exposure to poultry. However,
      specific host and exposure risk factors for disease are unknown, yet critical to
      design prevention measures. METHODS: In April-June 2013, we conducted a case
      control study in 8 Chinese provinces. Patients with laboratory-confirmed A(H7N9)
      (n = 89) were matched by age, sex, and neighborhood to controls (n = 339).
      Subjects completed a questionnaire on medical history and potential exposures,
      including poultry markets and other poultry exposure. We used conditional
      logistic regression to calculate matched and adjusted odds ratios (ORs) for the
      association of A(H7N9) virus infection with potential risk factors. RESULTS:
      Fifty-five percent of patients compared with 31% of controls reported any contact
      with poultry (matched OR [mOR], 7.8; 95% confidence interval [CI], 3.3-18.8).
      Sixty-seven percent of patients compared with 35% of controls visited a live
      poultry market (mOR, 5.4; CI, 3.0-9.7). Visiting live poultry markets increased
      risk of infection even after adjusting for poultry contact and other confounders
      (adjusted OR, 3.4; CI, 1.8-6.7). Backyard poultry were not associated with
      increased risk; 14% of cases did not report any poultry exposure or market visit.
      Obesity (mOR, 4.7; CI, 1.8-12.4), chronic obstructive pulmonary disease (mOR,
      2.7; CI, 1.1-6.9), and immunosuppressive medications (mOR, 9.0; CI, 1.7-47.2)
      were associated with A(H7N9) disease. CONCLUSION: Exposures to poultry in markets
      were associated with A(H7N9) virus infection, even without poultry contact. China
      should consider permanently closing live poultry markets or aggressively pursuing
      control measures to prevent spread of this emerging pathogen.

PMID- 24928294
TI  - Hospital-wide rollout of antimicrobial stewardship: a stepped-wedge randomized
      trial.
AB  - Our objective was to rigorously evaluate the impact of an antimicrobial
      stewardship audit-and-feedback intervention, via a stepped-wedge randomized
      trial. An effective intensive care unit (ICU) audit-and-feedback program was
      rolled out to 6 non-ICU services in a randomized sequence. The primary outcome
      was targeted antimicrobial utilization, using a negative binomial regression
      model to assess the impact of the intervention while accounting for secular and
      seasonal trends. The intervention was successfully transitioned, with high
      volumes of orders reviewed, suggestions made, and recommendations accepted. Among
      patients meeting stewardship review criteria, the intervention was associated
      with a large reduction in targeted antimicrobial utilization (-21%, P = .004);
      however, there was no significant change in targeted antibiotic use among all
      admitted patients (-1.2%, P = .9), and no reductions in overall costs and
      microbiologic outcomes. An ICU day 3 audit-and-feedback program can be
      successfully expanded hospital-wide, but broader benefits on non-ICU wards may
      require interventions earlier in the course of treatment. 

PMID- 24928295
TI  - Syphilis predicts HIV incidence among men and transgender women who have sex with
      men in a preexposure prophylaxis trial.
AB  - BACKGROUND: Syphilis infection may potentiate transmission of human
      immunodeficiency virus (HIV). We sought to determine the extent to which HIV
      acquisition was associated with syphilis infection within an HIV preexposure
      prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified
      that association. METHODS: The Preexposure Prophylaxis Initiative (iPrEx) study
      randomly assigned 2499 HIV-seronegative men and transgender women who have sex
      with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at
      screening and incidence during follow-up were measured. Hazard ratios for the
      effect of incident syphilis on HIV acquisition were calculated. The effect of
      FTC/TDF on incident syphilis and HIV acquisition was assessed. RESULTS: Of 2499
      individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening;
      333 (92.5%) had a positive confirmatory test, which did not differ between the
      arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the
      trial was 7.3 cases per 100 person-years. There was no difference in syphilis
      incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs
      6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by
      incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases
      per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6
      (95% confidence interval, 1.6-4.4; P < .001). There was no evidence for
      interaction between randomization to the FTC/TDF arm and incident syphilis on HIV
      incidence. CONCLUSIONS: In HIV-seronegative MSM, syphilis infection was
      associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should
      prompt providers to offer PrEP unless otherwise contraindicated.

PMID- 24928296
TI  - Highly efficient energy transfer from a carbonyl carotenoid to chlorophyll a in
      the main light harvesting complex of Chromera velia.
AB  - We report on energy transfer pathways in the main light-harvesting complex of
      photosynthetic relative of apicomplexan parasites, Chromera velia. This complex,
      denoted CLH, belongs to the family of FCP proteins and contains chlorophyll (Chl)
      a, violaxanthin, and the so far unidentified carbonyl carotenoid related to
      isofucoxanthin. The overall carotenoid-to-Chl-a energy transfer exhibits
      efficiency over 90% which is the largest among the FCP-like proteins studied so
      far. Three spectroscopically different isofucoxanthin-like molecules were
      identified in CLH, each having slightly different energy transfer efficiency that
      increases from isofucoxanthin-like molecules absorbing in the blue part of the
      spectrum to those absorbing in the reddest part of spectrum. Part of the energy
      transfer from carotenoids proceeds via the ultrafast S2 channel of both the
      violaxanthin and isofucoxanthin-like carotenoid, but major energy transfer
      pathway proceeds via the S1/ICT state of the isofucoxanthin-like carotenoid. Two
      S1/ICT-mediated channels characterized by time constants of ~0.5 and ~4ps were
      found. For the isofucoxanthin-like carotenoid excited at 480nm the slower channel
      dominates, while those excited at 540nm employs predominantly the fast 0.5ps
      channel. Comparing these data with the excited-state properties of the
      isofucoxanthin-like carotenoid in solution we conclude that, contrary to other
      members of the FCP family employing carbonyl carotenoids, CLH complex suppresses
      the charge transfer character of the S1/ICT state of the isofucoxanthin-like
      carotenoid to achieve the high carotenoid-to-Chl-a energy transfer efficiency. 

PMID- 24928297
TI  - Predicting the influence of multiple components on microbial inhibition using a
      logistic response model--a novel approach.
AB  - BACKGROUND: There are several synergistic methods available. However, there is a
      vast discrepancy in the interpretation of the synergistic results. Also, these
      synergistic methods do not assess the influence the tested components (drugs,
      plant and natural extracts), have upon one another, when more than two components
      are combined. METHODS: A modified checkerboard method was used to evaluate the
      synergistic potential of Heteropyxis natalensis, Melaleuca alternifolia, Mentha
      piperita and the green tea extract known as TEAVIGOTM. The synergistic
      combination was tested against the oral pathogens, Streptococcus mutans,
      Prevotella intermedia and Candida albicans. Inhibition data obtained from the
      checkerboard method, in the form of binary code, was used to compute a logistic
      response model with statistically significant results (p < 0.05). This
      information was used to construct a novel predictive inhibition model. RESULTS:
      Based on the predictive inhibition model for each microorganism, the oral
      pathogens tested were successfully inhibited (at 100% probability) with their
      respective synergistic combinations. The predictive inhibition model also
      provided information on the influence that different components have upon one
      another, and on the overall probability of inhibition. CONCLUSIONS: Using the
      logistic response model negates the need to 'calculate' synergism as the results
      are statistically significant. In successfully determining the influence multiple
      components have upon one another and their effect on microbial inhibition, a
      novel predictive model was established. This ability to screen multiple
      components may have far reaching effects in ethnopharmacology, agriculture and
      pharmaceuticals.

PMID- 24928298
TI  - [Arterial hypertension in Dakar: Prevalence, awareness, treatment, and control].
AB  - The aim of this study was to determine prevalence, awareness, treatment, and
      control of hypertension, and its risk factors in Dakar. Six hundred people aged
      20 and older, living in the city of Dakar were interviewed. This sample was
      constructed using the combined quota method in order to strive to
      representativeness of the target population. Prevalence of hypertension was
      27.50%. Quarter of those suffering from high blood pressure were aware of their
      problem, and among the latter, 61% said they were on treatment. However, of
      these, only 32% had controlled arterial blood pressure, that is less than 6% of
      those suffering from hypertension. Two factors were associated with hypertension,
      awareness, and treatment: age and the frequency of doctor visits. These results
      indicate that hypertension already constitutes a major health concern in the
      Senegalese capital. Detection can be considerably improved given that only a
      quarter of the hypertensives are aware of this problem. Compliance with
      treatments also appears particularly problematic. Public health policies should
      be quickly set up to minimize the consequences of this emerging burden. 

PMID- 24928299
TI  - Childhood leukemia mortality and farming exposure in South Korea: A national
      population-based birth cohort study.
AB  - OBJECTIVES: The aim of this study was to evaluate the relationship between
      leukemia mortality and exposure to farming among children in South Korea.
      METHODS: A retrospective cohort study of South Korean children was conducted
      using data collected by the national birth register between 1995 and 2006; these
      data were then individually linked to death data. A cohort of 6,479,406 children
      was followed from birth until either their death or until December 31, 2006. For
      surrogate measures of pesticide exposure, we used residence at birth, paternal
      occupation, and month of conception from the birth certificate. Farming and
      pesticide exposure indexes by county were calculated using information derived
      from the 2000 agricultural census. Poisson regression analyses were used to
      calculate rate ratios (RRs) of childhood leukemia deaths according to indices of
      exposure to agricultural pesticides after adjustment for potential confounders.
      RESULTS: In total 585 leukemia deaths were observed during the study period.
      Childhood leukemia mortality was significantly elevated in children born in rural
      areas (RR=1.43, 95%CI 1.09-1.86) compared to those in metropolises, and in
      counties with both the highest farming index (RR=1.33, 95%CI 1.04-1.69) and
      pesticide exposure index (RR=1.30, 95%CI 1.02-1.66) compared to those in the
      reference group. However, exposure-response associations were significant only in
      relation to the farming index. When the analyses were limited to rural areas, the
      risk of death from leukemia among boys conceived between spring and fall
      increased over those conceived in winter. CONCLUSIONS: Our results show an
      increase in mortality from childhood leukemia in rural areas; however, further
      studies are warranted to investigate the environmental factors contributing to
      the excess mortality from childhood leukemia in rural areas.

PMID- 24928300
TI  - Semi-adiabatic Shinnar-Le Roux pulses and their application to diffusion tensor
      imaging of humans at 7T.
AB  - The adiabatic Shinnar-Le Roux (SLR) algorithm for radiofrequency (RF) pulse
      design enables systematic control of pulse parameters such as bandwidth, RF
      energy distribution and duration. Some applications, such as diffusion-weighted
      imaging (DWI) at high magnetic fields, would benefit from RF pulses that can
      provide greater B1 insensitivity while adhering to echo time and specific
      absorption rate (SAR) limits. In this study, the adiabatic SLR algorithm was
      employed to generate 6-ms and 4-ms 180 degrees  semi-adiabatic RF pulses which
      were used to replace the refocusing pulses in a twice-refocused spin echo (TRSE)
      diffusion-weighted echo planar imaging (DW-EPI) sequence to create two versions
      of a twice-refocused adiabatic spin echo (TRASE) sequence. The two versions were
      designed for different trade-offs between adiabaticity and echo time. Since a
      pair of identical refocusing pulses is applied, the quadratic phase imposed by
      the first is unwound by the second, preserving the linear phase created by the
      excitation pulse. In vivo images of the human brain obtained at 7Testa (7T)
      demonstrate that both versions of the TRASE sequence developed in this study
      achieve more homogeneous signal in the diffusion-weighted images than the
      conventional TRSE sequence. Semi-adiabatic SLR pulses offer a more B1-insensitive
      solution for diffusion preparation at 7T, while operating within SAR constraints.
      This method may be coupled with any EPI readout trajectory and parallel imaging
      scheme to provide more uniform coverage for diffusion tensor imaging at 7T and
      3T. 

PMID- 24928301
TI  - A SVM-based quantitative fMRI method for resting-state functional network
      detection.
AB  - Resting-state functional magnetic resonance imaging (fMRI) aims to measure
      baseline neuronal connectivity independent of specific functional tasks and to
      capture changes in the connectivity due to neurological diseases. Most existing
      network detection methods rely on a fixed threshold to identify functionally
      connected voxels under the resting state. Due to fMRI non-stationarity, the
      threshold cannot adapt to variation of data characteristics across sessions and
      subjects, and generates unreliable mapping results. In this study, a new method
      is presented for resting-state fMRI data analysis. Specifically, the resting
      state network mapping is formulated as an outlier detection process that is
      implemented using one-class support vector machine (SVM). The results are refined
      by using a spatial-feature domain prototype selection method and two-class SVM
      reclassification. The final decision on each voxel is made by comparing its
      probabilities of functionally connected and unconnected instead of a threshold.
      Multiple features for resting-state analysis were extracted and examined using an
      SVM-based feature selection method, and the most representative features were
      identified. The proposed method was evaluated using synthetic and experimental
      fMRI data. A comparison study was also performed with independent component
      analysis (ICA) and correlation analysis. The experimental results show that the
      proposed method can provide comparable or better network detection performance
      than ICA and correlation analysis. The method is potentially applicable to
      various resting-state quantitative fMRI studies. 

PMID- 24928302
TI  - Multiplicative intrinsic component optimization (MICO) for MRI bias field
      estimation and tissue segmentation.
AB  - This paper proposes a new energy minimization method called multiplicative
      intrinsic component optimization (MICO) for joint bias field estimation and
      segmentation of magnetic resonance (MR) images. The proposed method takes full
      advantage of the decomposition of MR images into two multiplicative components,
      namely, the true image that characterizes a physical property of the tissues and
      the bias field that accounts for the intensity inhomogeneity, and their
      respective spatial properties. Bias field estimation and tissue segmentation are
      simultaneously achieved by an energy minimization process aimed to optimize the
      estimates of the two multiplicative components of an MR image. The bias field is
      iteratively optimized by using efficient matrix computations, which are verified
      to be numerically stable by matrix analysis. More importantly, the energy in our
      formulation is convex in each of its variables, which leads to the robustness of
      the proposed energy minimization algorithm. The MICO formulation can be naturally
      extended to 3D/4D tissue segmentation with spatial/sptatiotemporal
      regularization. Quantitative evaluations and comparisons with some popular
      softwares have demonstrated superior performance of MICO in terms of robustness
      and accuracy. 

PMID- 24928304
TI  - Vascular manifestations of pulmonary adenocarcinoma: a case report.

PMID- 24928303
TI  - Elevated C-reactive protein is associated with lower increase in knee muscle
      strength in patients with knee osteoarthritis: a 2-year follow-up study in the
      Amsterdam Osteoarthritis (AMS-OA) cohort.
AB  - INTRODUCTION: The aim of this study was to examine the associations of elevated
      serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with
      change in muscle strength in patients with established knee osteoarthritis (OA),
      at 2 years. METHODS: Data from 186 patients with knee OA were gathered at
      baseline and at 2-year follow-up. CRP (in milligrams per liter) and ESR (in
      millimeters per hour) were measured in serum from patients' blood. Strength of
      quadriceps and hamstrings muscles was assessed by using an isokinetic
      dynamometer. The association of inflammatory markers with change in knee muscle
      strength was analyzed by using uni- and multi-variate linear regression models.
      RESULTS: Patients with elevated CRP values at both baseline and 2-year follow-up
      exhibited a lower increase in knee muscle strength for a period of 2 years (beta
      = -0.22; P = 0.01) compared with the group with non-elevated levels at both times
      of assessment. The association persisted after adjustment for relevant
      confounders. Elevated ESR values at both times of assessment were not
      significantly associated with change in knee muscle strength (beta = -0.05; P =
      0.49). CONCLUSIONS: Our results indicate that elevated CRP values are related to
      a lower gain in muscle strength over time in patients with established knee OA.
      Although the mechanism to explain this relationship is not fully elucidated,
      these results suggest inflammation as a relevant factor influencing muscle
      strength in this group of patients.

PMID- 24928305
TI  - The open access movement: a chance to re-evaluate the peer review process?

PMID- 24928306
TI  - A cross-sectional questionnaire assessing patient and physician use of short-term
      prophylaxis for hereditary angioedema.
AB  - BACKGROUND: Current guidelines recommend short-term prophylaxis (STP) before
      invasive procedures to prevent hereditary angioedema (HAE) attacks; however,
      adherence to these guidelines may be variable because this indication lacks Food
      and Drug Administration approval in the United States. OBJECTIVE: To ascertain
      the STP experiences of patients with HAE and HAE-treating physicians. METHODS:
      Online questionnaires focusing on STP experiences were distributed by the US
      Hereditary Angioedema Association to the first 250 patients with HAE and to
      registered HAE-treating physicians. SAS 9.3 was used to perform descriptive
      statistics and to test the difference between patients who underwent procedures
      and those who did not using Pearson chi(2) test, Fisher exact test, and 2-sample
      t test. RESULTS: For the patient survey, 219 respondents met the criteria for HAE
      type 1 and 2; 37 (17%) underwent 66 invasive procedures, and all reported
      receiving STP. Eight patients (22%) reported failed STP, but only 3 required on
      demand therapy. For STP, anabolic steroids and plasma-derived C1 inhibitor were
      the most and second-most commonly used, respectively. For the physician survey,
      37 physicians reported caring for 433 patients with HAE. Depending on the
      procedure, 19% to 54% of physicians used STP and 30% to 86% prescribed on-demand
      therapy; 69% and 78% of physicians prescribed plasma-derived C1 inhibitor as STP
      for minimally invasive and invasive procedures, respectively. Physicians reported
      excellent efficacy for the STP treatments used. CONCLUSION: Physicians reported
      excellent outcomes using primarily newer STP therapies, namely plasma-derived C1
      inhibitor, which was discordant to patient-reported outcomes using older STP
      therapies, namely anabolic steroids. Well-controlled STP studies are needed to
      clarify use for patients with HAE in the United States.

PMID- 24928307
TI  - Perceptions regarding injection number and technique.

PMID- 24928308
TI  - Soluble DPP4 induces inflammation and proliferation of human smooth muscle cells
      via protease-activated receptor 2.
AB  - DPP4 is an ubiquitously expressed cell-surface protease that is shedded to the
      circulation as soluble DPP4 (sDPP4). We recently identified sDPP4 as a novel
      adipokine potentially linking obesity to the metabolic syndrome. The aim of this
      study was to investigate direct effects of sDPP4 on human vascular smooth muscle
      cells (hVSMCs) and to identify responsible signaling pathways. Using
      physiological concentrations of sDPP4, we could observe a concentration-dependent
      activation of ERK1/2 (3-fold) after 6h, which remained stable for up to 24h.
      Additionally, sDPP4 treatment induced a 1.5-fold phosphorylation of the NF-kappaB
      subunit p65. In accordance with sDPP4-induced stress and inflammatory signaling,
      sDPP4 also stimulates hVSMC proliferation. Furthermore we could observe an
      increased expression and secretion of pro-inflammatory cytokines like interleukin
      (IL)-6, IL-8 and MCP-1 (2.5-, 2.4- and 1.5-fold, respectively) by the sDPP4
      treatment. All direct effects of sDPP4 on signaling, proliferation and
      inflammation could completely be prevented by DPP4 inhibition. Bioinformatic
      analysis and signaling signature induced by sDPP4 suggest that sDPP4 might be an
      agonist for PAR2. After the silencing of PAR2, the sDPP4-induced ERK activation
      as well as the proliferation was totally abolished. Additionally, the sDPP4
      induced upregulation of IL-6 and IL-8 could completely be prevented by the PAR2
      silencing. In conclusion, we show for the first time that sDPP4 directly
      activates the MAPK and NF-kappaB signaling cascade involving PAR2 and resulting
      in the induction of inflammation and proliferation of hVSMC. Thus, our in vitro
      data might extend the current view of sDPP4 action and shed light on
      cardiovascular effects of DPP4-inhibitors. 

PMID- 24928310
TI  - A review of novel therapies for melanoma.
AB  - This review summarizes results from major recent trials regarding novel
      therapeutic agents in melanoma. The topics discussed include targeted therapy
      with BRAF (V-RAF murine sarcoma viral oncogene homolog B) inhibitors (vemurafenib
      and dabrafenib), MEK (mitogen-activated protein kinase kinase) inhibitors
      (trametinib), bcr-abl/c-kit/PDGF-R inhibitors (imatinib), and angiogenesis
      inhibitors (bevacizumab and aflibercept), as well as immunotherapy with anti-CTLA
      4 (anti-cytotoxic T-lymphocyte antigen-4) antibodies (ipilimumab), anti-PD (anti
      programmed death receptor) antibodies (nivolumab and lambrolizumab), and anti-PD
      L (anti-programmed death ligand) antibodies. Various combinations of these
      agents, as well as adjunctive GM-CSF (granulocyte-macrophage colony-stimulating
      factor), T-VEC (talimogene laherparepvec) oncolytic viruses, and novel
      chemotherapeutic agents, are also described. Despite the tremendous advances that
      these novel treatments have created, optimal therapeutic agent selection remains
      a highly individualized decision. Melanoma therapy has vastly progressed since
      the days when dacarbazine was the sole option for advanced melanoma patients. The
      molecular understanding of melanoma pathogenesis has yielded a brighter future
      for advanced melanoma patients.

PMID- 24928309
TI  - Netrin-1 improves post-injury cardiac function in vivo via DCC/NO-dependent
      preservation of mitochondrial integrity, while attenuating autophagy.
AB  - Reperfusion injury of the heart is a severe complication of angioplasty treatment
      of acute myocardial ischemia, for which no therapeutics are currently available.
      The present study aimed to identify whether and how a novel protein, netrin-1,
      induces cardioprotection in vivo during ischemia/reperfusion (I/R) injury. Wild
      type (WT) C57BL6/J mice were subjected to a 30 min coronary occlusion followed by
      a 24h reperfusion with vehicle (normal saline), netrin-1, UO126 (MEK1/2
      inhibitor), PTIO (nitric oxide/NO scavenger), netrin-1/UO126 or netrin-1/PTIO
      intraventricularly. Some were injected of netrin-1 via tail vein. Netrin-1 at
      5MUg/kg induced a substantial reduction in infarct size (19.7 +/- 5.0% from 41.3
      +/- 1.8% in the controls), and markedly improved cardiac function as measured by
      ejection fraction and fractional shortening from echocardiography. Experiments
      with mice deficient in netrin-1 receptor DCC (deleted in colorectal cancer, DCC+/
      ), or reperfusion with netrin-1/UO126 or netrin-1/PTIO, attenuated the protective
      effects of netrin-1, implicating intermediate roles of DCC, ERK1/2 and NO. Netrin
      1 induced phosphorylation of ERK1/2 and eNOS was abolished in DCC+/-mice.
      Electron spin resonance (ESR) determination of NO production from isolated left
      ventricles demonstrated that netrin-1 improves NO bioavailability, which was
      attenuated by UO126 or in DCC+/-mice, suggesting upstream roles of DCC and ERK1/2
      in NO production. Netrin-1 further reduced mitochondrial swelling and
      mitochondrial superoxide production, which was absent when co-treated with PTIO
      or UO126, or in DCC+/-mice, indicating critical roles of DCC, ERK1/2 and NO in
      preserving mitochondrial integrity. In a permanent coronary ligation model of
      myocardial infarction (MI) to assess post-MI remodeling, netrin-1 abolished the
      marked increase in autophagy. In summary, our data demonstrate robust
      cardioprotective effect of netrin-1 in vivo, as shown by reduced infarct size and
      improved cardiac function. Mechanistically, this protection is mediated by netrin
      1 receptor DCC, and NO dependent preservation of mitochondria. This work clearly
      establishes a therapeutic potential of netrin-1 for acute treatment of MI,
      perhaps also for chronic post-MI remodeling. This article is part of a Special
      Issue entitled: Autophagy and protein quality control in cardiometabolic
      diseases.

PMID- 24928311
TI  - Antibiotic treatment patterns across Europe in patients with complicated skin and
      soft-tissue infections due to meticillin-resistant Staphylococcus aureus: a plea
      for implementation of early switch and early discharge criteria.
AB  - This retrospective observational medical chart review aimed to describe country
      specific variations across Europe in real-world meticillin-resistant
      Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI)
      treatment patterns, antibiotic stewardship activity, and potential opportunities
      for early switch (ES) from intravenous (i.v.) to oral formulations and early
      discharge (ED) from hospital using standardised data collection and criteria and
      economic implications of these opportunities. Patients were randomly sampled from
      12 countries (Austria, Czech Republic, France, Germany, Greece, Ireland, Italy,
      Poland, Portugal, Slovakia, Spain and the UK), aged >=18 years, with documented
      MRSA cSSTI, hospitalised between 1 July 2010 and 30 June 2011, discharged alive
      by 31 July 2011. Of 1502 patients, 1468 received MRSA-targeted therapy.
      Intravenous-to-oral switch rates ranged from 2.0% to 20.2%, i.v. length of
      therapy from 10.1 to 18.6 days and hospital length of stay (LoS) from 15.2 to
      25.0 days across Europe. Of 341 sites, 82.9% had antibiotic steering committees,
      23.7% had i.v.-to-oral switch antibiotic protocols and 12.9% had ED protocols for
      MRSA cSSTI. ES and ED eligibility ranged from 12.0% (Slovakia) to 56.3% (Greece)
      and from 10% (Slovakia) to 48.2% (Portugal), respectively. Potential cost savings
      per ED-eligible patient ranged from ?414 (Slovakia) to ?2703 (France). MRSA cSSTI
      treatment patterns varied widely across countries, but further reductions in i.v.
      therapy, hospital LoS and associated costs could be realised. These data provide
      insight into clinical practice patterns across diverse European healthcare
      systems and identify potential opportunities for local clinicians and policy
      makers to improve clinical care and cost-effectiveness of this therapeutic area. 

PMID- 24928312
TI  - The lone S41 family C-terminal processing protease in Staphylococcus aureus is
      localized to the cell wall and contributes to virulence.
AB  - Staphylococcus aureus is a versatile pathogen of humans and a continued public
      health concern due to the rise and spread of multidrug-resistant strains. As part
      of an ongoing investigation into the pathogenic mechanisms of this organism we
      previously demonstrated that an intracellular N-terminal processing protease is
      required for S. aureus virulence. Following on from this, here we examine the
      role of CtpA, the lone C-terminal processing protease of S. aureus. CtpA, a
      member of the S41 family, is a serine protease whose homologues in Gram-negative
      bacteria have been implicated in a range of biological functions, including
      pathogenesis. We demonstrate that S. aureus CtpA is localized to the bacterial
      cell wall and expression of the ctpA gene is maximal upon exposure to conditions
      encountered during infection. Disruption of the ctpA gene leads to decreased heat
      tolerance and increased sensitivity when exposed to components of the host immune
      system. Finally we demonstrate that the ctpA(-) mutant strain is attenuated for
      virulence in a murine model of infection. Our results represent the first
      characterization of a C-terminal processing protease in a pathogenic Gram
      positive bacterium and show that it plays a critical role during infection. 

PMID- 24928314
TI  - High spatial resolution in vivo magnetic resonance imaging of the human eye,
      orbit, nervus opticus and optic nerve sheath at 7.0 Tesla.

PMID- 24928313
TI  - Vesicular stomatitis virus replicon expressing the VP2 outer capsid protein of
      bluetongue virus serotype 8 induces complete protection of sheep against
      challenge infection.
AB  - Bluetongue virus (BTV) is an arthropod-borne pathogen that causes an often fatal,
      hemorrhagic disease in ruminants. Different BTV serotypes occur throughout many
      temperate and tropical regions of the world. In 2006, BTV serotype 8 (BTV-8)
      emerged in Central and Northern Europe for the first time. Although this outbreak
      was eventually controlled using inactivated virus vaccines, the epidemic caused
      significant economic losses not only from the disease in livestock but also from
      trade restrictions. To date, BTV vaccines that allow simple serological
      discrimination of infected and vaccinated animals (DIVA) have not been approved
      for use in livestock. In this study, we generated recombinant RNA replicon
      particles based on single-cycle vesicular stomatitis virus (VSV) vectors.
      Immunization of sheep with infectious VSV replicon particles expressing the outer
      capsid VP2 protein of BTV-8 resulted in induction of BTV-8 serotype-specific
      neutralizing antibodies. After challenge with a virulent BTV-8 strain, the
      vaccinated animals neither developed signs of disease nor showed viremia. In
      contrast, immunization of sheep with recombinant VP5 - the second outer capsid
      protein of BTV - did not confer protection. Discrimination of infected from
      vaccinated animals was readily achieved using an ELISA for detection of
      antibodies against the VP7 antigen. These data indicate that VSV replicon
      particles potentially represent a safe and efficacious vaccine platform with
      which to control future outbreaks by BTV-8 or other serotypes, especially in
      previously non-endemic regions where discrimination between vaccinated and
      infected animals is crucial.

PMID- 24928316
TI  - Factors associated with voice-related quality of life among teachers with voice
      complaints.
AB  - This study evaluates whether the scores on the voice-related quality of life (V
      RQOL) and voice activity and participation profile (VAPP) instruments show
      similar associations with socio-demographic characteristics, voice complaint
      characteristics, work-related factors, health conditions and consequences of
      voice complaints; and to assess agreement between V-RQOL and VAPP. In 12 primary
      and secondary public schools in Bogota, we conducted a cross-sectional study
      among 438 Colombian school teachers with voice complaints. Participants filled
      out a questionnaire on socio-demographic characteristics, voice complaint
      characteristics, work-related factors, health conditions, economic consequences
      of voice complaints, and voice-related quality of life, which was assessed using
      the V-RQOL and the VAPP. The factors associated with the scores on the V-RQOL and
      VAAP were analysed using multiple linear regression. Assessment of agreement
      between the V-RQOL and VAPP scores was performed using the Bland-Altman plot.
      Simple linear regression analysis was used to examine the relationship between
      VAPP and V-RQOL. Results showed that individual and work-related factors that
      were associated with the scores derived from the questionnaires were similar for
      the two instruments, namely severity of voice complaints, auditory symptoms,
      hearing impairment, class size, and poor acoustics in the workplace. The
      associations between the score and the economic consequences of voice complaints
      were also similar for the two instruments. The V-RQOL and VAPP scores were
      strongly associated with one another and showed high agreement with regard to
      teachers' perception of quality of life. These findings suggest that factors
      identified as being associated with the scores on the V-RQOL and VAPP are shared
      by the two instruments, showing that their approaches to quality-of-life
      assessment are similar. Both scales were strongly associated with one another and
      showed high agreement. LEARNING OUTCOMES: Identify factors associated with scores
      on voice-related quality of life (V-RQOL) and voice activity and participation
      profile (VAPP). Identify whether the scores on V-RQOL and VAPP show similar
      associations with individual and work-related factors. Explain agreement between
      the scores on V-RQOL and VAPP.

PMID- 24928315
TI  - Neuroprotective effects of C3 exoenzyme in excitotoxic retinopathy.
AB  - The purpose of this study is to evaluate the neuroprotective effects of C3
      exoenzyme (C3) on N-methyl-d-aspartate (NMDA)-induced retinopathy in rats. C3 was
      expressed in Escherichia. coli and purified by affinity chromatography.
      Immunofluorescence was performed in NIH 3T3 cells treated with C3 to verify the
      cellular uptake of the protein. NMDA was injected intravitreally into rat eyes
      with or without C3. At various time points after injection, eyes were enucleated.
      Hematoxylin/eosin staining was performed on retina cross-sections for
      morphological analysis. Survival and apoptosis of cells in the ganglion cell
      layer (GCL) were assessed by cresyl violet staining and terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) on retina flat-mounts. RhoA levels in
      retina cells were evaluated by Western blot to detect C3 uptake in vivo. The
      cellular uptake of C3 was verified by immunofluorescence. Damage including a
      decrease in inner plexiform layer (IPL) thickness and reduction of cell density
      in the GCL, corresponding to apoptosis of neurons, was induced by intravitreal
      injection of NMDA. Protection against this damage was observed following co
      injection of C3 and NMDA. RhoA ADP-ribosylation induced by C3 was confirmed by
      Western blot. Our results suggest that C3 exerts neuroprotective effects against
      excitotoxic damage induced by NMDA. 

PMID- 24928317
TI  - Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis
      is driven by high synovial activation and reflected by S100A8/A9 serum levels.
AB  - OBJECTIVE: Synovitis is evident in a substantial subpopulation of patients with
      osteoarthritis (OA) and is associated with development of pathophysiology.
      Recently we have shown that adipose-derived stem cells (ASC) inhibit joint
      destruction in collagenase-induced experimental OA (CIOA). In the current study
      we explored the role of synovitis and alarmins S100A8/A9 in the immunomodulatory
      capacity of ASCs in experimental OA. METHOD: CIOA, characterized by synovitis,
      and surgical DMM (destabilization of medial meniscus) OA were treated locally
      with ASCs. Synovial activation, cartilage damage and osteophyte size were
      measured on histological sections. Cytokines in synovial washouts and serum were
      determined using Luminex or enzyme-linked immunosorbent assay (S100A8/A9), mRNA
      levels with reverse-transcriptase (RT)-qPCR. RESULTS: Local administration of
      ASCs at various time-points (days 7 or 14) after DMM induction had no effect on
      OA pathology. At day 7 of CIOA, already 6 h after ASC injection mRNA expression
      of pro-inflammatory mediators S100A8/A9, interleukin-1beta (IL-1beta) and KC was
      down-regulated in the synovium. IL-1beta protein, although low, was down
      regulated by ASC-treatment of CIOA. S100A8/A9 protein levels were very high at 6
      and 48 h and were decreased by ASC-treatment. The protective action of ASC
      treatment in CIOA was only found when high synovial inflammation was present at
      the time of deposition which was reflected by high serum S100A8/A9 levels.
      Finally, successful treatment resulted in significantly lower levels of serum
      S100A8/A9. CONCLUSION: Our study indicates that synovial activation rapidly
      drives anti-inflammatory and protective effects of intra-articularly deposited
      ASCs in experimental OA which is reflected by decreased S100A8/A9 levels.

PMID- 24928318
TI  - Effect of interval-training exercise on subchondral bone in a chemically-induced
      osteoarthritis model.
AB  - OBJECTIVES: The role of subchondral bone in osteoarthritis (OA) development is
      well admitted. Cross-talk between subchondral bone and cartilage may be disrupted
      in OA, leading to altered subchondral bone remodeling. Osteocytes are involved in
      bone remodeling control and could play a key role in OA progression. Our purpose
      of this study was to evaluate the preventive effect of interval-training exercise
      on subchondral bone and osteocyte in monosodium iodoacetate (MIA) model of
      experimental OA. METHODS: At baseline, 48 male Wistar rats (8 weeks old) were
      separated into two groups: interval-training exercise or no exercise for 10
      weeks. After this training period, each group was divided into two subgroups: MIA
      injected knee (1 mg/100 MUl saline) and saline-injected knee. Four weeks later,
      rats were sacrificed and carefully dissected. Evaluated parameters were:
      cartilage degeneration by OA scoring, bone mineral density (BMD) by Dual energy X
      ray Absorptiometry (DXA), trabecular subchondral bone microarchitecture by micro
      computed tomography (MUCT), cortical subchondral bone lacunar osteocyte occupancy
      (by Toluidine Blue staining) and cleaved caspase-3 positive apoptosis (by
      epifluorescence). RESULTS: Our results showed deleterious effects of MIA on
      cartilage. OA induced a decrease in proximal tibia (PT) BMD which was prevented
      by exercise. Exercise induced increase in full osteocyte lacunae surface and
      osteocyte occupancy (+60%) of cortical subchondral bone independently of OA.
      Osteocyte apoptosis (<1%) in cortical subchondral bone was not different whatever
      the group at sacrifice. CONCLUSION: Our results suggest that preliminary interval
      training improved BMD and osteocytes lacunar occupancy in subchondral bone. Our
      interval-training did not prevent MIA-induced cartilage degeneration.

PMID- 24928319
TI  - Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and
      future therapeutic strategies.
AB  - Currently, osteoarthritis (OA) is considered a disease of the entire joint, which
      is not simply a process of wear and tear but rather abnormal remodelling and
      joint failure of an organ. The bone-cartilage interface is therefore a
      functioning synergistic unit, with a close physical association between
      subchondral bone and cartilage suggesting the existence of biochemical and
      molecular crosstalk across the OA interface. The crosstalk at the bone-cartilage
      interface may be elevated in OA in vivo and in vitro. Increased vascularisation
      and formation of microcracks associated with abnormal bone remodelling in joints
      during OA facilitate molecular transport from cartilage to bone and vice versa.
      Recent reports suggest that several critical signalling pathways and biological
      factors are key regulators and activate cellular and molecular processes in
      crosstalk among joint compartments. Therapeutic interventions including
      angiogenesis inhibitors, agonists/antagonists of molecules and drugs targeting
      bone remodelling are potential candidates for this interaction. This review
      summarised the premise for the presence of crosstalk in bone-cartilage interface
      as well as the current knowledge of the major signalling pathways and molecular
      interactions that regulate OA progression. A better understanding of crosstalk in
      bone-cartilage interface may lead to development of more effective strategies for
      treating OA patients. 

PMID- 24928320
TI  - Endothelial dysfunction in conduit arteries and in microcirculation. Novel
      therapeutic approaches.
AB  - The vascular endothelium not only is a single monolayer of cells between the
      vessel lumen and the intimal wall, but also plays an important role by
      controlling vascular function and structure mainly via the production of nitric
      oxide (NO). The so called "cardiovascular risk factors" are associated with
      endothelial dysfunction, that reduces NO bioavailability, increases oxidative
      stress, and promotes inflammation contributing therefore to the development of
      atherosclerosis. The significant role of endothelial dysfunction in the
      development of atherosclerosis emphasizes the need for efficient therapeutic
      interventions. During the last years statins, angiotensin-converting enzyme
      inhibitors, angiotensin-receptor antagonists, antioxidants, beta-blockers and
      insulin sensitizers have been evaluated for their ability to restore endothelial
      function (Briasoulis et al., 2012). As there is not a straightforward
      relationship between therapeutic interventions and improvement of endothelial
      function but rather a complicated interrelationship between multiple cellular and
      sub-cellular targets, research has been focused on the understanding of the
      underlying mechanisms. Moreover, the development of novel diagnostic invasive and
      non-invasive methods has allowed the early detection of endothelial dysfunction
      expanding the role of therapeutic interventions and our knowledge. In the current
      review we present the available data concerning the contribution of endothelial
      dysfunction to atherogenesis and review the methods that assess endothelial
      function with a view to understand the multiple targets of therapeutic
      interventions. Finally we focus on the classic and novel therapeutic approaches
      aiming to improve endothelial dysfunction and the underlying mechanisms. 

PMID- 24928321
TI  - A novel cell-penetrating peptide to facilitate intercellular transport of fused
      proteins.
AB  - Cell-based delivery of cell penetrating peptides (CPPs) could represent a new
      platform for intracellular peptide delivery to local tissues. Expressed CPPs,
      coupled to a secretory signal peptide (SP), can support intercellular transport.
      However, low secretion efficiency, which may correlate with the positive charge
      of most CPPs, has emerged as one of the main impediments for efficient
      intercellular transport. We have reported that a modified Tat-based CPP (Tatm)
      with reduced positive charge is secreted efficiently, but its transduction
      activity was greatly reduced. We now show that a triple repeat of Tatm (Tatm3x)
      with an elongated alpha-helical amphipathic structure enhances transduction
      activity and simultaneously retains its secretion efficacy, although passage
      through the secretory pathway reduces its cell-penetrating activity. SP-Tatm3x
      supports intercellular transport of fused fluorescent proteins, as well as cell
      entry and function of a pro-apoptotic peptide. In addition, SP-Tatm3x largely
      escapes RNA inhibition, which is identified as another potential impediment to
      CPP-mediated intercellular transport. Expression of SP-Tatm3x in heparan sulfate
      proteoglycan-negative cells further improves its transduction activity. These
      results demonstrate the feasibility of intercellular transport of proteins, but
      further work is needed to better understand the reduction of cell-penetrating
      activity associated with secretion of CPP-fusion proteins. 

PMID- 24928322
TI  - IRF5-mediated signaling and implications for SLE.
AB  - Transcription of the type I IFN genes is regulated by members of the Interferon
      Regulatory Factor (IRF) family of transcription factors, composed in humans of 9
      distinct proteins. In addition to IRF3 and IRF7, the transcription factor IRF5
      has been shown to be involved in type I IFN production and interestingly,
      polymorphisms of the IRF5 gene in humans can result in risk or protective
      haplotypes with regard to SLE susceptibility. In addition to regulation of type I
      IFN expression, IRF5 is involved in other signaling pathways, including IgG
      switching in B cells, macrophage polarization and apoptosis, and its role in SLE
      pathogenesis may therefore not be limited to dysregulated control of IFN
      expression. In this review we will comprehensively discuss the role of IRF5 in
      immune-mediated responses and its potential multifaceted role in conferring SLE
      susceptibility. 

PMID- 24928323
TI  - A phase I study of PRO131921, a novel anti-CD20 monoclonal antibody in patients
      with relapsed/refractory CD20+ indolent NHL: correlation between clinical
      responses and AUC pharmacokinetics.
AB  - PRO131921 is a third-generation, humanized anti-CD20 monoclonal antibody with
      increased antibody-dependent cytotoxicity and complement-dependent cytotoxicity
      compared to rituximab. In this phase I study, PRO131921 was administered as a
      single agent to patients with CD20+, relapsed or refractory, indolent non-Hodgkin
      lymphoma (NHL) who had been treated with a prior rituximab-containing regimen.
      The primary aim of this study was safety and tolerability of PRO131921. The
      secondary aim of the study, and focus of this report, was to determine the
      pharmacokinetics (PK) profile of PRO131921 and establish a correlation between
      drug exposure and clinical efficacy. Patients were treated with PRO131921 by
      intravenous infusion weekly for 4 weeks and the dose was escalated based on
      safety in a 3+3 design. Twenty-four patients were treated with PRO131921 at doses
      from 25mg/m(2) to 800 mg/m(2). Analysis of PK data demonstrated a correlation
      between higher normalized drug exposure (normalized AUC) and tumor shrinkage (p =
      .0035). Also, normalized AUC levels were higher among responders and subjects
      displaying tumor shrinkage versus subjects progressing or showing no regression
      (p = 0.030). In conclusion, PRO131921 demonstrated clinical activity in rituximab
      relapsed and refractory indolent NHL patients. The observation that higher
      normalized AUC may be associated with improved clinical responses has potential
      implications in future trials of monoclonal antibody-based therapies, and
      emphasizes the importance of early PK studies to optimize antibody efficacy.

PMID- 24928324
TI  - Systemic injection of TLR1/2 agonist improves adoptive antigen-specific T cell
      therapy in glioma-bearing mice.
AB  - Adoptive immunotherapy is an attractive strategy for glioma treatment. However,
      some obstacles still need be overcome. In this study, GL261-bearing mice treated
      with adoptively transferred antigen-specific T cells and systemic injection of
      bacterial lipoprotein (BLP), a TLR1/2 agonist, got a long-term survival and even
      immune protection. By analyzing adoptive T cells, it was found that BLP
      maintained T cell survival, proliferation and anti-tumor efficacy in the brains
      of tumor-bearing hosts. Moreover, tumor microenvironment was modified by up
      regulating IFN-gamma-secreting CD8+ T cells and down-regulating MDSC, which might
      be related with high CXCL10 and low CCL2 expression. In addition, TLR2 deficiency
      abrogated therapeutic effect with increased MDSC accumulation and decreased IFN
      gamma-secreting CD8+ T cells in the brains. Thus, the systemic injection of BLP
      could improve the adoptive T cell therapy by maintaining T cell persistence,
      modifying the tumor microenvironment and even inducing systemic anti-tumor
      immunity, which might offer a clinically promising immunotherapeutic strategy for
      glioma. 

PMID- 24928325
TI  - The lectin pathway of complement: advantage or disadvantage in HIV pathogenesis?
AB  - The pattern recognition molecules of the lectin complement pathway are important
      components of the innate immune system with known functions in host-virus
      interactions. This paper summarizes current knowledge of how these intriguing
      molecules, including mannose-binding lectin (MBL), Ficolin-1, -2 and -3, and
      collectin-11 (CL-11) may influence HIV-pathogenesis. It has been demonstrated
      that MBL is capable of binding and neutralizing HIV and may affect host
      susceptibility to HIV infection and disease progression. In addition, MBL may
      cause variations in the host immune response against HIV. Ficolin-1, -2 and -3
      and CL-11 could have similar functions in HIV infection as the ficolins have been
      shown to play a role in other viral infections, and CL-11 resembles MBL and the
      ficolins in structure and binding capacity. 

PMID- 24928326
TI  - Morphometric sex estimation from 3D computed tomography os coxae model and its
      validation in skeletal remains.
AB  - In the last decade, the advances in imaging technologies have intensified the use
      of multislice computed tomography (MSCT) for anthropological purposes. The
      published literature has proved it to be a suitable tool for establishing
      sexually dimorphic characteristics in different anatomical areas. In this
      context, the main purpose of the present study was to explore the accuracy of
      traditional morphometric method when applied to data acquired in three
      dimensional (3D) reconstructed os coxae of living Spanish population, to develop
      a series of statistically robust patterns for sex assessment and to test their
      validity in innominate remains. For this purpose, 150 volume-rendered innominate
      CT scans were selected to examine nine interlandmark linear distances by means of
      descriptive statistics and discriminant function analyses (DFA) employing the
      jackknife procedure for cross-validations. Five measurements were sexually
      dimorphic. Acetabular diameter was the single most accurate predictor. This,
      combined with innominate height and innominate breadth, contributed very
      significantly to sex estimation. Overall, classification accuracies were 89.3
      95.3 % (89.3-94.7 % after cross-validation), with a sex-bias lower than 5 %. The
      second validation approach performed on a sample of 96 individuals from another
      contemporary Spanish reference collection comprising dry bones showed the high
      percentage of accurate classification (83.3-95.8 %). In conclusion, the
      assessment of sex using cross-sectional MSCT images of the os coxae is possible
      and the discriminant functions obtained on Spanish living individuals can also be
      effective for estimating sex from skeletal remains.

PMID- 24928327
TI  - Applications of sensory feedback in motorized upper extremity prosthesis: a
      review.
AB  - Dexterous hand movement is possible due to closed loop control dependent on
      efferent motor output and afferent sensory feedback. This control strategy is
      significantly altered in those with upper limb amputation as sensations of touch
      and movement are inherently lost. For upper limb prosthetic users, the absence of
      sensory feedback impedes efficient use of the prosthesis and is highlighted as a
      major factor contributing to user rejection of myoelectric prostheses. Numerous
      sensory feedback systems have been proposed in literature to address this gap in
      prosthetic control; however, these systems have yet to be implemented for long
      term use. Methodologies for communicating prosthetic grasp and touch information
      are reviewed, including discussion of selected designs and test results. With a
      focus on clinical and translational challenges, this review highlights and
      compares techniques employed to provide amputees with sensory feedback.
      Additionally, promising future directions are discussed and highlighted.

PMID- 24928328
TI  - Polymorphic variants of adrenoceptors: pharmacology, physiology, and role in
      disease.
AB  - The human genome encodes nine different adrenoceptor genes. These are grouped
      into three families, namely, the alpha1-, alpha2-, and beta-adrenoceptors, with
      three family members each. Adrenoceptors are expressed by most cell types of the
      human body and are primary targets of the catecholamines epinephrine and
      norepinephrine that are released from the sympathetic nervous system during its
      activation. Upon catecholamine binding, adrenoceptors change conformation, couple
      to and activate G proteins, and thereby initiate various intracellular signaling
      cascades. As the primary receivers and transducers of sympathetic activation,
      adrenoceptors have a central role in human physiology and disease and are
      important targets for widely used drugs. All nine adrenoceptor subtypes display
      substantial genetic variation, both in their coding sequence as well as in
      adjacent regions. Despite the fact that some of the adrenoceptor variants range
      among the most frequently studied genetic variants assessed in pharmacogenetics
      to date, their functional relevance remains ill defined in many cases. A
      substantial fraction of the associations reported from early candidate gene
      approaches have not subsequently been confirmed in different cohorts or in genome
      wide association studies, which have increasingly been conducted in recent years.
      This review aims to provide a comprehensive overview of all adrenoceptor variants
      that have reproducibly been detected in the larger genome sequencing efforts. We
      evaluate these variants with respect to the modulation of receptor function and
      expression and discuss their role in physiology and disease. 

PMID- 24928329
TI  - The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in
      models of disease.
AB  - The P2X7 receptor is a trimeric ATP-gated cation channel found predominantly, but
      not exclusively, on immune cells. P2X7 activation results in a number of
      downstream events, including the release of proinflammatory mediators and cell
      death and proliferation. As such, P2X7 plays important roles in various
      inflammatory, immune, neurologic and musculoskeletal disorders. This review
      focuses on the use of P2X7 antagonists in rodent models of neurologic disease and
      injury, inflammation, and musculoskeletal and other disorders. The cloning and
      characterization of human, rat, mouse, guinea pig, dog, and Rhesus macaque P2X7,
      as well as recent observations regarding the gating and permeability of P2X7, are
      discussed. Furthermore, this review discusses polymorphic and splice variants of
      P2X7, as well as the generation and use of P2X7 knockout mice. Recent evidence
      for emerging signaling pathways downstream of P2X7 activation and the growing
      list of negative and positive modulators of P2X7 activation and expression are
      also described. In addition, the use of P2X7 antagonists in numerous rodent
      models of disease is extensively summarized. Finally, the use of P2X7 antagonists
      in clinical trials in humans and future directions exploring P2X7 as a
      therapeutic target are described. 

PMID- 24928330
TI  - Whither core outcome sets?

PMID- 24928331
TI  - Simultaneous splenectomy during liver transplantation augments anti-viral therapy
      in patients infected with hepatitis C virus.
AB  - BACKGROUND: Simultaneous splenectomy in liver transplantation (LT) is selectively
      indicated because of splenoportal venous thromboses and increased sepsis.
      Therefore, its impact should be further investigated. METHODS: Of the 160 liver
      transplant patients, only 40 underwent simultaneous splenectomy.
      Clinicopathologic characteristics and outcomes were compared between the
      splenectomy and non-splenectomy group using retrospective analysis. RESULTS:
      Although the groups were similar and had no significant difference in the intra-
      and postoperative data, non-splenectomy group had more male patients. However,
      splenectomy group showed significantly higher platelet and leukocyte counts at 1
      month and 6 months after the transplantation and higher hepatitis C virus anti
      viral therapy completion. Furthermore, 3 patients developed portal or splenic
      vein thrombosis during the postoperative follow-up, but the overall survival rate
      did not significantly differ between these groups. CONCLUSION: Simultaneous
      splenectomy in LT can be safely performed, particularly in patients with
      hepatitis C virus cirrhosis, small-for-size grafts, hypersplenism, and ABO blood
      group incompatible (ABO - incompatible) LT.

PMID- 24928332
TI  - The physiological effects of hyperosmolar resuscitation: 5% vs 3% hypertonic
      saline.
AB  - BACKGROUND: Use of 5% normal saline (NS) is gaining renewed interest. The primary
      aim of our study was to compare the physiological effects after the
      administration of different concentrations of hypertonic saline (3% vs 5%NS) in
      the initial resuscitation of trauma. METHODS: We performed a retrospective
      analysis of a prospectively collected database of all trauma patients who
      received hypertonic saline during initial resuscitation. Medical records were
      reviewed for serum electrolytes and serum osmolarity, coagulation parameters,
      complications, and mortality. RESULTS: A total of 212 patients were included in
      the study, of which 170 patients received 5%NS and 42 patients received 3%NS.
      Both groups were similar in age (41.16 +/- 19 vs 44.17 + 23.6; P = .45) and ISS
      score (26 [17 to 29] vs 25 [16 to 27]; P = .6). Mean serum osmolarity (316 +/-
      20.3 vs 294 +/- 22.5; P = .02) and serum sodium levels (143 +/- 8.6 vs 137 +/-
      10.9; P < .001) remained higher in the 5%NS group within 72 hours of admission.
      The pH was lower in the 5%NS group compared with the 3%NS group at 24 hours (7.29
      +/- .12 vs 7.33 +/- .12; P = .01); however, at 48 and 72 hours (7.40 +/- .07 vs
      7.41 +/- .07; P = .7), no difference was found. There was no difference in blood
      products requirement (1,734 vs 2,253 mL; P = .11) between the 2 groups.
      CONCLUSIONS: The 5%NS has sustained higher serum osmolarity and serum sodium
      concentration within the first 72 hours without any increase in adverse effects
      in comparison with 3%NS.

PMID- 24928333
TI  - Splenectomy in trauma patients is associated with an increased risk of
      postoperative type II diabetes: a nationwide population-based study.
AB  - BACKGROUND: Animal studies indicate that splenocytes may act as precursors of
      beta-islet secretory cells in the pancreas. This study aimed to assess the risk
      of postoperative type II diabetes after splenectomy in trauma patients. METHODS:
      We used data from the Taiwan National Health Insurance hospitalized claims. Study
      1 included 3,723 patients receiving splenectomy and 3,723 matched patients
      receiving other types of abdominal surgery. Study 2 included 5,996 patients with
      spleen injury and 5,996 matched patients with other types of abdominal injury.
      The hazard ratio for diabetes was estimated using the matched Cox proportional
      hazard regression model. RESULTS: In trauma patients after surgery, those who
      received splenectomy had a 2-fold higher risk of diabetes compared with patients
      without splenectomy after a 3-year follow-up period. In the nonoperative group,
      there was no difference in diabetes risk between patients with splenic injury and
      those with other types of injury. CONCLUSIONS: Splenectomy was associated with an
      increased risk of postoperative type II diabetes in trauma patients. Thus, there
      may be a role for the spleen in the development of diabetes.

PMID- 24928334
TI  - Early thromboembolic prophylaxis in patients with blunt solid abdominal organ
      injuries undergoing nonoperative management: is it safe?
AB  - BACKGROUND: The aim of this study was to compare the safety of early (<=48
      hours), intermediate (48 to 72 hours), and late (>=72 hours) venous
      thromboembolism prophylaxis in patients with blunt abdominal solid organ injury
      managed nonoperatively. METHODS: We performed a 6-year (2006 to 2011)
      retrospective review of all trauma patients with blunt abdominal solid organ
      injuries. Patients were matched using propensity score matching in a 2:1:1
      (early:intermediate:late) for age, gender, systolic blood pressure, Glasgow Coma
      Scale, Injury Severity Score, and type and grade of organs injured. Our primary
      outcome measures were: hemorrhage complications and need for intervention
      (operative intervention and/or angioembolization). RESULTS: A total of 116
      patients (58 early, 29 intermediate, and 29 late) were included. There were no
      differences in age (P = .5), Injury Severity Score (P = .6), type (P = .1), and
      grade of injury of the organ (P = .6) between the 3 groups. There were 67 liver
      (43.2%), 63 spleen (40.6%), 49 kidney (31.6%), and 24 multiple solid organ
      (15.4%) injuries. There was no difference in operative intervention (P = .8) and
      postprophylaxis blood transfusion (P = .3) between the 3 groups. CONCLUSIONS:
      Early enoxaparin-based anticoagulation may be a safe option in trauma patients
      with blunt solid organ injury. This study showed no significant correlation
      between early anticoagulation and development of bleeding complications.

PMID- 24928335
TI  - Relationship between homocysteine and coronary artery disease. Results from a
      large prospective cohort study.
AB  - BACKGROUND: Coronary artery disease (CAD) still represents the major cause of
      mortality in developed countries. Large research programs have been focused on
      the identification of new risk factors to prevent CAD, with special attention to
      homocysteine (Hcy), due to the known associated increased thrombogenicity,
      oxidative stress status and endothelial dysfunction. However, controversy still
      exists on the association between Hcy and CAD. Therefore, aim of the current
      study was to investigate the association of Hcy with the prevalence and extent of
      CAD in a large consecutive cohort of patients undergoing coronary angiography.
      METHODS: Our population is represented by a total of 3056 consecutive patients
      undergoing coronary angiography between at the Azienda Ospedaliera "Maggiore
      della Carita", Novara, Italy. Fasting samples were collected for homocysteine
      levels assessment. Coronary disease was defined for at least 1 vessel
      stenosis>50% as evaluated by QCA. RESULTS: Study population was divided according
      to Hcy tertiles (<13,3, 13,3-18.2, >18.2nmol/ml). High plasmatic level of
      homocysteine was related with age (p<0.001), male gender (p<0.001), hypertension
      (p<0.001) renal failure (p<0.001), family history of CAD (p<0.001), previous
      cerebrovascular accident (p<0.001), previous MI (p=0.002), previous CABG
      (p=0.003), ejection fraction (p<0.001), higher baseline creatinine (p<0.001), in
      treatment with nitrates (p<0.001), calcium antagonists (p<0.001), diuretics
      (p<0.001), Ace inhibitors (ACE-I) (p=0.006), Clopidogrel (p=0.05), haemoglobin
      (p=0.001), white blood cells (WBC) count (p=0.008), total cholesterol (p=0.04),
      Low-Density Lipoproteins (LDL) (p=0.01). A significant relationship was found
      between Hcy levels and the extent of coronary artery disease (71.8% vs 77.8% vs
      77.4%, OR[95%CI]=1.18[1.11-1.252.], p<0.001 and severe CAD (23.6% vs 29.5% vs
      32.1%, OR [95%CI]=1.275 [1.209-1.344], p<0.001). Elevated Hcy was significantly
      associated with increased risk of CAD (adjusted OR[95%CI]=1.087[1.009-1.171],
      p=0.02 and severe CAD (adjusted OR [95%CI]=1.07 [1.01-1.16, P=0.04]). The results
      were confirmed in the majority of high risk subsets of patients. CONCLUSIONS:
      This study showed that high levels of plasmatic Hcy are independently associated
      with CAD. Further large studies are certainly needed to explore the adjunctive
      benefits from vitamin administration in patients with elevated Hcy to prevent the
      occurrence and progression of CAD.

PMID- 24928337
TI  - Pupil-expansion ring implantation through a 0.9 mm incision.
AB  - Disposable square and hexagonal Bhattacharjee pupil-expansion rings are made of 5
      0 nylon, have notches at the corners, and flanges at the sides in a single 0.1 mm
      thin plane. To insert the ring, a flange is held with a 23-gauge forceps and the
      ring is inserted through a 0.9 mm (20-gauge) or larger main- or side-port
      incision. Alternate flanges are tucked under the iris using a Kuglen hook. A 23
      gauge forceps and an iris hook can also be used to tuck the flanges bimanually.
      The ring is removed by disengaging 2 notches and pulling it out of a 0.9 mm (20
      gauge) incision. No snagging of the incision occurs at insertion or removal. No
      injector is required. The device is useful in standard coaxial
      phacoemulsification, femtosecond laser-assisted cataract surgery, biaxial
      microincision cataract surgery (MICS), coaxial sub-2.0 mm MICS, and small-pupil
      microincision vitreous surgery and in eyes with shallow anterior chambers.
      FINANCIAL DISCLOSURE: Dr. Bhattacharjee has a pending international patent
      application (PCT-WIPO) for the pupil-expansion devices.

PMID- 24928338
TI  - Comparison of vilanterol, a novel long-acting beta2 agonist, with placebo and a
      salmeterol reference arm in asthma uncontrolled by inhaled corticosteroids.
AB  - BACKGROUND: Current maintenance therapies for asthma require twice-daily dosing.
      Vilanterol (VI) is a novel long-acting beta2 agonist, under development in
      combination with fluticasone furoate, a new inhaled corticosteroid (ICS).
      Findings from a previous 4-week study suggested that VI has inherent 24-hour
      activity and is therefore suitable for once-daily dosing. The study described
      here was a double-blind, double-dummy, randomised, placebo-controlled trial, the
      aim of which was to assess the efficacy of once-daily VI compared with placebo in
      patients with persistent asthma. The primary endpoint was change from baseline in
      24-hour weighted mean forced expiratory volume in 1 second after 12 weeks of
      treatment vs. placebo. An active control arm received salmeterol (SAL) twice
      daily. All patients were maintained on a stable background dose of ICS. RESULTS:
      Patients (n = 347) received VI, placebo or SAL (1:1:1). For the primary endpoint,
      substantial improvements in lung function were seen with VI (359 ml), SAL (283
      ml) and placebo (289 ml). There were no statistically significant treatment
      differences between either the VI (70 ml, P = 0.244) or SAL (-6 ml, P = 0.926)
      groups and placebo. Both active treatments were well tolerated, with similarly
      low rates of treatment-related adverse events compared with placebo. No treatment
      related serious adverse events occurred. CONCLUSIONS: This study failed to show a
      treatment difference between VI and placebo for the primary endpoint, in the
      presence of a placebo response of unforeseen magnitude. Because the placebo
      response was so large, it is not possible to draw meaningful conclusions from the
      data. The reason for this magnitude of effect is unclear but it may reflect
      increased compliance with the anti-inflammatory therapy regimen during the
      treatment period. TRIAL REGISTRATION: NCT01181895 at ClinicalTrials.gov.

PMID- 24928339
TI  - Trends in leisure time physical activity, smoking, body mass index and alcohol
      consumption in Danish adults with and without diabetes: a repeat cross-sectional
      national survey covering the years 2000 to 2010.
AB  - AIMS: In recent decades there has been an increased focus on non-pharmacological
      treatment of diabetes. The aim of this study was to investigate trends in leisure
      time physical activity (PA), smoking, body mass index (BMI), and alcohol
      consumption reported in 2000, 2005 and 2010 by Danish subjects with diabetes.
      METHODS: Data comprised level of leisure time PA (inactive; moderate active;
      medium active; high active); smoking; BMI; and alcohol consumption, provided by
      The Danish Health and Morbidity Surveys. Participants older than 45 years with or
      without diabetes were included from cross-sectional analyses from 2000, 2005 and
      2010. RESULTS: In participants with diabetes, leisure time PA levels increased
      from 2000 to 2010: The percentage of those that were physically active increased
      from 53.5% to 78.2% (p<0.001; women) and from 67.8% to 79.1% (p=0.01; men). The
      prevalence of daily smokers was reduced from 27.2% to 16.4%, p=0.015, in women
      with diabetes. In men with diabetes, BMI increased from 27.2 +/- 4.0 to 28.6 +/-
      5.1 kgm(-2), p=0.003, and men who exceeded the maximum recommendation for alcohol
      consumption increased from 9.4% to 19.0%, p=0.007. The leisure time PA level was
      reduced in participants with diabetes compared to participants without diabetes
      throughout the study. CONCLUSIONS: The percentage of physically active Danish
      participants older than 45 years with diabetes increased from 2000 to 2010, and
      the most beneficial trends in life style were observed among the women. These
      trends may have serious implications for cardiovascular risk in Danish patients
      with diabetes.

PMID- 24928340
TI  - Ectodysplasin research--where to next?
AB  - Ectodysplasin (Eda) is the most studied tumor necrosis ligand in the field of
      developmental biology. In all vertebrates studied so far, inactivating germline
      mutations in Eda lead to the genetic disease called hypohidrotic ectodermal
      dysplasia (HED). In humans, HED is a life-threatening condition in particular in
      infants due to absent or severely reduced sweating leading to hyperthermia. HED
      is also characterized by sparse hair, and oligo- or anodontia. Research of the
      Eda pathway has not only increased our knowledge on ectodermal appendage
      development and etiology of developmental disorders, but also on evolution of
      several vertebrate species including humankind. Studies on mouse and dog models
      of HED has led to one of the most stunning breakthroughs in applied developmental
      biology research by showing that a short-term treatment of neonates with a
      synthetic ligand corrects many of the HED-associated traits. Eighteen years after
      the identification of EDA as the causative gene in HED, a phase II trial aiming
      at permanent correction of the disease is now ongoing. This review summarizes the
      latest discoveries in the Eda field and points to areas that need further
      investigation such as the possible involvement of Eda in cell migration, stem
      cell maintenance, or cancer. 

PMID- 24928341
TI  - The impact of inflammatory rheumatic diseases on the presentation, severity, and
      outcome of acute coronary syndrome.
AB  - Patients with inflammatory rheumatic diseases (IRD) have a high burden of
      cardiovascular disease (CVD), leading to increased mortality and morbidity.
      However, it is not clear whether increased CVD mortality in IRD is due to a
      higher incidence or worse outcome of cardiovascular events (higher case
      fatality). In this observational case-control study, we assessed the outcome of
      acute coronary syndrome (ACS) in patients with IRDs compared to matched controls
      without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS),
      a large, national, real-life registry detailing the extent, severity, and outcome
      of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified
      with IRD, including 11 patients with rheumatoid arthritis, five patients with
      systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis
      (AS), and one patient with psoriatic arthritis (PsA). The study patients were
      compared to 120 matched control patients (adjusted for age and risk factors for
      CVD) without IRD. Compared to controls, IRD patients had similar clinical
      presentation and similar type of ACS and received identical initial treatment at
      the ER. The two groups had comparable rates of complications including major
      adverse cardiovascular events (death, recurrent myocardial infarction, stroke,
      major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and
      control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%,
      respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%,
      respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in
      patients with IRD is not worse than that of control, supporting the higher
      prevalence of CVD in this population as the cause for their excess mortality.

PMID- 24928342
TI  - Cardiac autonomic functions in children with familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory
      disease in the world. The long-term effects of subclinical inflammation in FMF
      are not well recognized. Some studies have suggested that FMF is associated with
      cardiac autonomic dysfunction in adult FMF patients. The objective of this study
      was to investigate the cardiac autonomic functions in pediatric FMF patients by
      using several autonomic tests. Thirty-five patients with FMF and 35 healthy
      controls were enrolled in this cross-sectional study. Demographic data, disease
      specific data, and orthostatic symptoms were recorded. In all participants, 12
      lead electrocardiography (ECG), 24 h ambulatory electrocardiographic monitoring,
      transthoracic echocardiography, treadmill exercise test, and head upright tilt
      table (HUTT) test were performed. The heart rate recovery (HRR) indices of the
      two groups were similar. Also, chronotropic response was similar in both groups.
      The time-domain parameters of heart rate variability (HRV) were similar in both
      groups, except mean RR (p = 0.024). Frequencies of ventricular and
      supraventricular ectopic stimuli were similar in both groups. There were no
      statistically significant differences between the groups in average QT and
      average corrected QT interval length, average QT interval dispersion, and average
      QT corrected dispersion. There was no significant difference between the two
      groups regarding the ratio of clinical dysautonomic reactions on HUTT. However,
      we observed a significantly higher rate of dysautonomic reactions on HUTT in
      patients with exertional leg pain than that in patients without (p = 0.013). When
      the fractal dimension of time curves were compared, FMF patients exhibited
      significantly lower diastolic blood pressure parameters than controls in response
      to HUTT. Cardiovascular autonomic dysfunction in children with FMF is not
      prominent. Particularly, patients with exertional leg pain are more prone to have
      dysautonomic features. Further studies are needed to elucidate the exact
      mechanisms leading to impaired cardiac autonomic functions in FMF. 

PMID- 24928343
TI  - Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis:
      DIANA study.
AB  - Autonomic neuropathy (AN) is a risk predictor for sudden cardiac death in
      rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, the impact of
      most commonly employed disease-modifying anti-rheumatic drug (DMARD) therapy on
      autonomic neuropathy in rheumatic diseases is not known. Hence, we investigated
      the efficacy of DMARDs on autonomic neuropathy in RA and AS. We performed
      autonomic function assessment in 60 patients in this open-label, 12-week pilot
      study including 42 patients with RA, 18 with AS, and 30 aged-matched healthy
      subjects. The methodology included assessment of cardiovascular autonomic reflex
      tests according to Ewing. Parasympathetic dysfunction was established by
      performing three tests: heart rate response to deep breathing, standing, and
      Valsalva tests. Sympathetic dysfunction was examined by applying two tests: blood
      pressure response to standing and handgrip tests. Sudomotor function was assessed
      by Sudoscan. Cardiovascular reflex tests were impaired significantly among the
      patients as compared to healthy subjects (p < 0.05). Autonomic neuropathy was
      more pronounced in biologic-naive RA and AS patients. After treatment with
      combination synthetic DMARDs, parasympathetic, and sudomotor dysfunction
      significantly (p < 0.05) improved in RA and AS. Biologic DMARDs significantly
      improved parasympathetic, sympathetic and peripheral sympathetic autonomic
      neuropathy (p < 0.05) in biologic-naive RA and AS patients. In conclusion,
      synthetic DMARDs improved parasympathetic and sudomotor dysfunction in both DMARD
      naive RA and AS patients. However, biologic DMARDs improved parasympathetic,
      sympathetic and sudomotor dysfunction to a greater extent than synthetic DMARDs
      in both RA and AS patients.

PMID- 24928344
TI  - Interleukin-6 promotes systemic lupus erythematosus progression with Treg
      suppression approach in a murine systemic lupus erythematosus model.
AB  - Our aim is to reveal the role of interleukin 6 (IL-6) in the pathogenesis of
      systemic lupus erythematosus (SLE) in a murine model of SLE. Normal female
      C57BL/6 mice were immunized with syngeneic-activated lymphocyte-derived DNA (ALD
      DNA) to induce SLE. Non-immunized mice were used as control. SLE-associated
      markers, including anti-double-stranded DNA (anti-dsDNA) Abs, urine protein, and
      kidney histopathology, were assayed to ensure the induction of the disease.
      Compared with control mice, ALD-DNA immunized mice exhibited high levels of anti
      dsDNA Abs, IL-6 expression in vivo and in vitro. We also found that IL-6 knockout
      (IL-6KO) mice were resistant to ALD-DNA-induced SLE. The activation of CD4(+) T
      cells in immunized IL-6KO mice was lower than in immunized wild-type (Wt) mice.
      Intracellular cytokine staining showed that Foxp3 expression in immunized IL-6KO
      mice was higher than in immunized Wt mice, which might be associated with the
      disease severity. We further discovered that ALD-DNA-stimulated dendritic cells
      supernatants could result in higher IL-6 and TNF-alpha expression and could
      suppress Foxp3 expression. In addition, blocking IL-6 could up-regulate Foxp3
      expression. Therefore, our findings show that IL-6 promotes the progression of
      SLE via suppressing Treg differentiation. 

PMID- 24928345
TI  - Adalimumab decreases aortic stiffness independently of its effect in disease
      activity in patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity
      and mortality attributed to traditional cardiovascular risk factors and/or the
      chronic systemic inflammation. We investigated the effect of a TNF antagonist
      (adalimumab-ADA) on aortic stiffness in RA patients. We studied 18 RA patients
      with active disease despite therapy with disease modifying antirheumatic drugs
      (DMARDs), treated with ADA (alone or in combination with DMARDs) for 12 weeks.
      Disease activity markers as well as aortic stiffness indices (carotid-femoral
      pulse wave velocity-PWV, augmentation index-AIx), were measured at baseline and
      at the end of treatment. Eighteen RA patients treated with methotrexate (MTX)
      were included as controls. Patients were categorized as responders (decrease of
      Disease Activity Score-DAS28 > 1.2) or nonresponders. There was a statistically
      significant decrease in PWV (from 8.18 +/- 2.03 to 7.01 +/- 1.78 m/s, p =
      0.00006) and DAS28 (from 6.65 +/- 1.22 to 4.69 +/- 1.46, p = 0.00007) in RA
      patients treated with ADA. The decrease in PWV was observed both in responders (n
      = 12) and nonresponders (n = 6). Multivariate analysis showed that the decrease
      of PWV was independent of changes in disease activity or other parameters. There
      was no significant change in PWV in patients treated with MTX (from 8.87 +/- 1.91
      to 8.41 +/- 2.17, p = 0.29). No significant change in AIx or traditional
      cardiovascular risk factors was observed. Treatment with ADA significantly
      reduced aortic stiffness in RA patients regardless of their response to therapy.
      These findings imply a direct protective effect of ADA in vascular wall in RA
      patients.

PMID- 24928346
TI  - Induction of vitiligo after imiquimod treatment of condylomata acuminata.
AB  - BACKGROUND: Condylomata acuminata (genital warts) is the most common sexually
      transmitted disease, and imiquimod is the sole FDA-approved medication for
      combating this condition. Vitiligo associated with imiquimod treatment of
      condylomata acuminata is rare. CASE PRESENTATION: A 28-year-old male with
      condylomata acuminata of the penis presented to our clinic. After removing his
      condylomata acuminata, we advised him to use imiquimod 5% cream to prevent
      relapse. When he presented to our clinic again about 12 weeks later, he
      complained of vitiligo patches on his penis and scrotum. Physical examination
      showed vitiligo patches involving the glans penis, shaft of the penis, and
      scrotum, and remaining pigmented areas within the plaques of vitiligo.A skin
      biopsy of the dorsal surface of the penis showed a complete absence of
      melanocytes and melanin granules in the basal layer; the dermis was normal.
      CONCLUSION: This is the first report of a case of imiquimod-induced vitiligo
      diagnosed by histopathological examination. This adverse effect should be
      considered when dermatologists prescribe this medication.

PMID- 24928347
TI  - Analysis of thermal and structural properties of germanate glasses co-doped with
      Yb(3+)/Tb(3+) ions.
AB  - In the work the new glass compositions in the GeO2-GaO-BaO system have been
      prepared and thermal, structural properties of in germanate glasses co-doped with
      Yb(3+)/Tb(3+)ions were studied. Glasses were obtained by conventional high
      temperature melt-quenching technique. The study of the crystallization kinetics
      processes of glasses co-doped with 0.7Yb2O3:0.7Tb2O3 was performed with DSC
      measurements. The activation energies have been calculated using Freedman
      analysis and verified with the Flynn-Wall-Ozawa method. In this order, the DSC
      curves have been registered with different heating rates, between 5 and 15
      degrees/min. The structure of fabricated glasses has been studied by infrared and
      Raman spectroscopes. The effect of heat treatment on the structural properties
      was determined. In all glass samples the dominated infrared absorbance band at
      800cm(-1) corresponds to asymmetric stretching motions of GeO4 tetrahedra
      containing bridging (Ge-O(Ge)) and non-bridging (Ge-O(-)) oxygens. Additionally,
      the influence of heat treatment on the luminescent properties was evaluated.
      Strong luminescence at 489, 543, 586 and 621nm corresponding to (5)D4->(7)FJ
      (J=6, 5, 4, 3) transitions was measured. The highest upconversion emission
      intensity was obtained in the germanate glass co-doped with 0.7Yb2O3/0.7Tb2O3. 

PMID- 24928348
TI  - Evidence for the healthy immigrant effect in older Chinese immigrants: a cross
      sectional study.
AB  - BACKGROUND: Previous work has found that first-generation immigrants to developed
      nations tend to have better health than individuals born in the host country. We
      examined the evidence for the healthy immigrant effect and convergence of health
      status between Chinese immigrants (n = 147) and U.S. born whites (n = 167)
      participating in the cross-sectional Community Assessment of Freeway Exposure and
      Health study and residing in the same neighborhoods. METHODS: We used bivariate
      and multivariate models to compare disease prevalence and clinical biomarkers.
      RESULTS: Despite an older average age and lower socioeconomic status, Chinese
      immigrants were less likely to have asthma (OR = 0.20, 95% CI = 0.09-0.48) or
      cardiovascular disease (OR = 0.44, 95% CI = 0.20-0.94), had lower body mass index
      (BMI), lower inflammation biomarker levels, lower average sex-adjusted low
      density lipoprotein (LDL) cholesterol, and higher average sex-adjusted high
      density lipoprotein (HDL) cholesterol. However, there was no significant
      difference in the prevalence of diabetes or hypertension. Duration of time in the
      U.S. was related to cardiovascular disease and asthma but was not associated with
      diabetes, hypertension, BMI, HDL cholesterol, LDL cholesterol, socioeconomic
      status, or health behaviors. CONCLUSIONS: The lower CVD and asthma prevalence
      among the Chinese immigrants may be partially attributed to healthier diets, more
      physical activity, lower BMI, and less exposure to cigarette smoke. First
      generation immigrant status may be protective even after about two decades.

PMID- 24928349
TI  - Purinergic signaling negatively regulates activity of an olfactory receptor in an
      odorant-dependent manner.
AB  - Extracellular purines and pyrimidines are important signaling molecules that
      mediate diverse biological functions via cell surface purinergic receptors.
      Although purinergic modulation to olfactory activity has been reported, cell
      specific expression and action of purinergic receptors deserve further
      exploration. We physiologically characterized expression of purinergic receptors
      in a set of olfactory sensory neurons that are responsive to both acetophenone
      and benzaldehyde (AB-OSNs). Sparsely distributed in the most ventral olfactory
      receptor zone, AB-OSNs were activated by P2 purinergic receptor agonists but not
      by P1 purinergic receptor agonist adenosine. Both P2X-selective agonist
      alpha,beta-methylene ATP and P2Y-selective agonist uridine 5'-triphosphate (UTP)
      were stimulatory to AB-OSNs, indicating expression of both P2X and P2Y purinergic
      receptors in AB-OSNs. Pharmacological characterization of receptor specificity
      using various P2X and P2Y agonists and antagonists illustrated that P2X1 and P2Y2
      receptors played major roles in purinergic signaling in AB-OSNs. Interestingly,
      the results of purinergic modulation to acetophenone-evoked responses were
      different from those to benzaldehyde-evoked responses within the same neurons.
      Activation of P2X1 receptors had more profound inhibitory effects on benzaldehyde
      evoked intracellular calcium elevation than on acetophenone-evoked responses
      within the same neurons, and the reverse was true when P2Y2 receptors were
      activated. Cross-adaptation data showed that acetophenone and benzaldehyde bound
      to the same olfactory receptor. Thus, our study has demonstrated that purinergic
      signaling of P2X and P2Y receptors has different effects on olfactory
      transduction mediated by a defined olfactory receptor and the consequences of
      purinergic modulation of olfactory activity might depend on stereotypic
      structures of the odorant-receptor complex. 

PMID- 24928350
TI  - The auditory-evoked arousal modulates motor cortex excitability.
AB  - Arousal enhances the readiness to process sensory information and respond to it.
      Rapid increment of arousal, referred to as arousal reaction or startle, increases
      the level of attention and the chance of survival. Arousal reaction is known to
      originate from the brainstem ascending reticular activating system and to
      modulate neuronal activity throughout the central nervous system. In the present
      study we investigated the effect of arousal on the central motor system by
      synchronizing transcranial magnetic stimulation (TMS) with acoustically evoked
      N100 potential. Because of the widespread cortical distribution of N100 to a
      sudden acoustic stimulus it is thought to be related to arousal reaction. Eight
      healthy subjects participated in this study. TMS was focused on the primary motor
      cortex utilizing neuronavigation. Trains of four identical loud tones repeated at
      1-s intervals were delivered to the right ear and TMS was randomly placed after
      one tone in the train. The motor-evoked potentials (MEPs) were measured from the
      contralateral first dorsal interosseous muscle. The MEPs evoked by TMS timed at
      N100 after the first tone in train were significantly (p<.001) larger in
      comparison with the control stimulation without a preceding sound or stimulation
      placed after the N100, i.e., 120% of the N100 interstimulus interval. Also, the
      MEPs following the second tone were significantly weaker (p<.05) when compared
      with the MEPs following the first tone. Our findings suggest that acoustic
      arousal reaction facilitates, not only the activation of sensory cortices, but
      also simultaneously the central motor system. 

PMID- 24928351
TI  - Generation of induced neurons by direct reprogramming in the mammalian cochlea.
AB  - Primary auditory neurons (ANs) in the mammalian cochlea play a critical role in
      hearing as they transmit auditory information in the form of electrical signals
      from mechanosensory cochlear hair cells in the inner ear to the brainstem. Their
      progressive degeneration is associated with disease conditions, excessive noise
      exposure and aging. Replacement of ANs, which lack the ability to regenerate
      spontaneously, would have a significant impact on research and advancement in
      cochlear implants in addition to the amelioration of hearing impairment. The aim
      of this study was to induce a neuronal phenotype in endogenous non-neural cells
      in the cochlea, which is the essential organ of hearing. Overexpression of a
      neurogenic basic helix-loop-helix transcription factor, Ascl1, in the cochlear
      non-sensory epithelial cells induced neurons at high efficiency at embryonic,
      postnatal and juvenile stages. Moreover, induced neurons showed typical
      properties of neuron morphology, gene expression and electrophysiology. Our data
      indicate that Ascl1 alone or Ascl1 and NeuroD1 is sufficient to reprogram
      cochlear non-sensory epithelial cells into functional neurons. Generation of
      neurons from non-neural cells in the cochlea is an important step for the
      regeneration of ANs in the mature mammalian cochlea. 

PMID- 24928352
TI  - IL-17A contributes to brain ischemia reperfusion injury through calpain-TRPC6
      pathway in mice.
AB  - Interleukin (IL)-17A plays an important role in the cerebral ischemia/reperfusion
      (I/R) injury. However, the mechanisms are still largely unknown. Calpain
      transient receptor potential canonical (subtype) 6 (TRPC6) signaling pathway has
      been recently found to be implicated in brain I/R injury. However, their
      relationships with IL-17A remain unknown. This study aims to test whether this
      important signaling has correlation with IL-17A and how they led to the neuronal
      damage in I/R injury. In the present study, mice were subjected to middle
      cerebral artery occlusion (60 min) followed by reperfusion for different times.
      Infarct volumes and neurological deficits were examined. Real-time PCR (RT-PCR)
      and Western blotting were conducted to detect IL-17A expression in the penumbral
      brain tissue. Activation of calpain and expression of TRPC6 were also studied. We
      found that cerebral I/R significantly increased the levels of IL-17A at 1, 3 and
      6 days after reperfusion in the penumbral area. IL-17A knockout or anti-IL-17A
      monoclonal antibody (mAb) significantly reduced whereas recombinant mouse-IL-17A
      (rIL-17A) increased the activation of calpain at 3 days after reperfusion. The
      calpain specific inhibitor calpeptin significantly increased TRPC6 expression.
      Brain injury and neurological deficits were largely abrogated by IL-17A knockout,
      anti-IL-17A mAb or calpeptin. Recombinant IL-17A treatment markedly increased I/R
      injury. In conclusion, IL-17A may promote brain I/R injury through the increase
      of calpain-mediated TRPC6 proteolysis. These results further outline a novel
      neuroprotective strategy with increased effectiveness for the inhibition of
      excess brain IL-17A in cerebral I/R injury.

PMID- 24928353
TI  - Enhanced excitatory synaptic network activity following transient group I
      metabotropic glutamate activation.
AB  - Prolonged activation of group I metabotropic glutamate receptors (mGluRs) using
      the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces long-lasting changes
      in the CA3 region of the hippocampal slice. Changes in CA3 pyramidal neuron
      excitability that follow DHPG exposure result in abnormal network activity
      manifest by epileptiform activity that consists of interictal and longer lasting
      ictal epileptiform discharges. In this study we evaluated changes in synaptic
      activity of CA3 neurons in rat hippocampal slices that occurred after exposure to
      DHPG. Whole-cell voltage-clamp recordings were made from visually identified CA3
      neurons in control artificial cerebrospinal fluid at times greater than 1h after
      DHPG exposure. Compared to control slices, neurons from slices exposed to DHPG
      showed enhanced amplitude and frequency of spontaneously occurring excitatory
      postsynaptic currents (EPSCs) without a concurrent change in inhibitory
      postsynaptic current (IPSC) amplitude or frequency. Miniature EPSCs were not
      affected by DHPG exposure but mIPSCs occurred less frequently and were of reduced
      amplitude. IPSCs recorded in the presence of ionotropic glutamate receptor
      blockade occurred less frequently in neurons that had been exposed to DHPG.
      Monosynaptic-evoked IPSPs were also reduced in amplitude in neurons that had been
      exposed to DHPG. Taken together, these findings demonstrated an enhanced network
      excitability of the CA3 region and failure of compensatory synaptic inhibition.
      We propose that prolonged activation of group I mGluR that may occur under
      conditions of pathological glutamate release results in long-lasting changes in
      CA3 synaptic network activity and epileptiform activity driven by excessive
      synaptic excitation. 

PMID- 24928354
TI  - Heterochromatin variants in human karyotypes: a possible association with
      reproductive failure.
AB  - Heterochromatin variants are commonly found during cytogenetic examinations, and
      chromosomes 1, 9, 16 and Y are commonly involved in these variations. These
      variants are believed to be clinically insignificant variations in human
      karyotypes. Nevertheless, reproductive failure has been frequently discussed as
      possibly being associated with these variants. Various authors have reported a
      significantly elevated incidence of these variants in individuals with idiopathic
      reproductive failure compared with individuals with no such history. This study
      compared the incidence of heterochromatin variants in individuals with idiopathic
      reproductive failure (n=1036) with that of a control group of healthy fetuses
      (n=995) indicated for prenatal karyotype examination solely based on the advanced
      ages of their mothers. The heterochromatin variants occurred more frequently in
      the reproductive failure group than in the controls (P=0.006). Regarding
      individual chromosomes, chromosome 9 variants were most frequently found in the
      study and control groups, and they also occurred more frequently in the
      reproductive failure group. The most significant difference between the study and
      control groups was found for the 9qh+ variant (P=0.026), and although the results
      are statistically significant, the cause of this phenomenon remains unknown.

PMID- 24928355
TI  - Early trophoblast invasion and placentation in women with different PCOS
      phenotypes.
AB  - This study evaluated the impact of different phenotypes of polycystic ovary
      syndrome (PCOS) on early trophoblast invasion and placentation. Pregnant patients
      with different PCOS phenotypes and healthy pregnant women, matched for age and
      body mass index, were enrolled. Histological analysis of trophoblastic and
      decidual tissue and macroscopic and microscopic assessment of the placentas were
      performed. Implantation-site vessels with endovascular trophoblast differed
      significantly among PCOS phenotypes. Placental weight, thickness, density and
      fetal-placental weight ratio were significantly different in the full-blown and
      non-polycystic ovary (PCO) phenotypes versus the ovulatory and non
      hyperandrogenic phenotypes. The incidence of macroscopic placental lesions was
      only significantly different between controls and the full-blown and non-PCO
      phenotypes. The overall incidence of microscopic placental lesions was
      significantly different among PCOS phenotypes and was significantly higher in the
      full-blown and non-PCO phenotypes than in the ovulatory and non-hyperandrogenic
      phenotypes. The rates of chorionic villitis and intervillositis were
      significantly higher in full-blown and non-PCO phenotypes than in ovulatory and
      non-hyperandrogenic phenotypes. In conclusion, alterations in early trophoblast
      invasion and placentation observed in PCOS vary widely according to phenotype. 

PMID- 24928356
TI  - Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases
      the risk of idiopathic male infertility.
AB  - N-acetyltransferase (NAT2) is a phase-II xenobiotic-metabolizing enzyme
      participating in the detoxification of toxic arylamines, aromatic amines and
      hydrazines. The present study was designed to investigate whether two common
      single-nucleotide polymorphisms (SNP) of the NAT2 gene (481C>T, rs1799929;
      590G>A, rs1799930) are associated with susceptibility to idiopathic male
      infertility and to assess if the risk is modified by oxidant and antioxidant
      exposures. A total 430 DNA samples (203 infertile patients and 227 fertile men)
      were genotyped for the polymorphisms by PCR and restriction fragment length
      polymorphism. No association was found between the NAT2 polymorphisms and
      idiopathic male infertility. However, gene-environment interaction analysis
      revealed that a low-acetylation genotype, 590GA, was significantly associated
      with increased disease risk in men who had environmental risk factors such as
      cigarette smoking (OR 1.71, 95% CI 1.02-2.87, P = 0.042), alcohol abuse (OR 2.14,
      95% CI 1.08-4.27, P = 0.029) and low fruit/vegetable intake (OR 1.68, 95% CI 1.01
      2.79, P = 0.04). This pilot study found, as far as is known for the first time,
      that the polymorphism 590G>A of NAT2 is a novel genetic marker for susceptibility
      to idiopathic male infertility, but the risk is potentiated by exposure to
      various environmental oxidants. 

PMID- 24928357
TI  - [Fair use of tests in health sciences].
AB  - Standardized measurement instruments (tests) have become an essential tool in
      health sciences. The concept of equity in the development, adaptation and
      administration of psychometric tests was first introduced in "Standards for
      Educational and Psychological Testing" published in 1999 by the American
      Educational Research Association, the American Psychological Association, and the
      National Council on Measurement in Education. Despite its importance, this
      concept has been scarcely used in epidemiology and public health. Consequently,
      this methodological note aims to explain the concept of equity in testing and to
      provide tools and indications to detect and solve their inequitable use.

PMID- 24928358
TI  - Tuberculous botryomycosis of the hand: case report.
AB  - We report a case of a 17-year-old boy who presented with botryoid lesions of both
      hands. These lesions resembled those of cutaneous botryomycosis. We treated him
      with surgical debridement and were unable to isolate infective agents initially.
      However, 3 months later Mycobacterium tuberculosis grew in the culture. One year
      of antituberculous drug therapy resulted in healing of the lesions. 

PMID- 24928359
TI  - Comparison of arthroplasties with or without bone tunnel creation for thumb basal
      joint arthritis: a randomized controlled trial.
AB  - PURPOSE: To compare the results for treatment of basal thumb osteoarthritis with
      and without the use of a bone tunnel at the base of the first metacarpal.
      METHODS: Women aged 40 years or older with stage IV osteoarthritis were
      randomized to 1 of 2 treatments. Patients were evaluated preoperatively and
      postoperatively at 3 and 12 months by assessing pain, outcome function measures,
      range of motion, strength, time to return to work or activities, satisfaction
      with the results, and complication rate. RESULTS: A total of 79 patients were
      enrolled in this study. Three months after surgery, Patient-Rated Wrist and Hand
      Evaluation pain and total scores were significantly improved in the bone tunnel
      group compared with the tunnel-free group. At 12 months, however, we found no
      significant differences for all outcome scores between groups. In addition, we
      observed no significant differences between groups in strength, duration to
      return to work or activities, patient satisfaction, and complication rates.
      CONCLUSIONS: After the bone tunnel technique, patients have better function and
      less pain 3 months after surgery than do those in the non-bone tunnel group,
      which indicates faster recovery. However, 12 months after surgery, the functional
      outcome was similar. Because of faster recovery, we prefer the bone tunnel
      technique in the treatment of stage IV osteoarthritis. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic I.

PMID- 24928360
TI  - Effect of non-symmetric waveform on conduction block induced by high-frequency
      (kHz) biphasic stimulation in unmyelinated axon.
AB  - The effect of a non-symmetric waveform on nerve conduction block induced by high
      frequency biphasic stimulation is investigated using a lumped circuit model of
      the unmyelinated axon based on Hodgkin-Huxley equations. The simulation results
      reveal that the block threshold monotonically increases with the stimulation
      frequency for the symmetric stimulation waveform. However, a non-monotonic
      relationship between block threshold and stimulation frequency is observed when
      the stimulation waveform is non-symmetric. Constant activation of potassium
      channels by the high-frequency stimulation results in the increase of block
      threshold with increasing frequency. The non-symmetric waveform with a positive
      pulse 0.4-0.8 MUs longer than the negative pulse blocks axonal conduction by
      hyperpolarizing the membrane and causes a decrease in block threshold as the
      frequency increases above 12-16 kHz. On the other hand, the non-symmetric
      waveform with a negative pulse 0.4-0.8 MUs longer than the positive pulse blocks
      axonal conduction by depolarizing the membrane and causes a decrease in block
      threshold as the frequency increases above 40-53 kHz. This simulation study is
      important for understanding the potential mechanisms underlying the nerve block
      observed in animal studies, and may also help to design new animal experiments to
      further improve the nerve block method for clinical applications. 

PMID- 24928361
TI  - Assessment of early and late dysphagia using videofluoroscopy and quality of life
      questionnaires in patients with head and neck cancer treated with radiation
      therapy.
AB  - BACKGORUND: The aim of this study was to evaluate dysphagia in patients with head
      and neck cancer (HNC) undergoing three-dimensional conformal radiation therapy
      using objective and subjective tools simultaneously and to associate the clinical
      correlates of dysphagia with dosimetric parameters. METHODS: Twenty patients were
      included in the study. The primary tumor and the involved lymph nodes (LN) were
      treated with 66-70 Gy, the uninvolved LN were treated with 46-50 Gy. Six
      swallowing structures were identified: the superior pharyngeal constrictor muscle
      (SPCM), the middle pharyngeal constrictor muscle (MPCM), the inferior pharyngeal
      constrictor muscle (IPCM), the base of tongue (BOT), the larynx and the proximal
      esophageal sphincter (PES). Dysphagia was evaluated using videofluoroscopy and
      European Organization for Research and Treatment of Cancer (EORTC) QoL
      questionnaire (QLQ-C30) and supplemental EORTC QoL module for HNC (QLQ-H&N35).
      The evaluations were performed before treatment, at 3 months and at 6 months
      following treatment. RESULTS: On objective evaluation, the Dmax for the larynx
      and the sub-structures of the PCM were correlated with impaired lingual movement,
      BOT weakness and proximal esophageal stricture at 3 months, whereas the V65, the
      V70and the Dmax for the larynx was correlated with BOT weakness and the V65, the
      V70, the Dmax or the Dmean for the sub-structures of the PCM were correlated with
      impaired lingual movement, BOT weakness, reduced laryngeal elevation, reduced
      epiglottic inversion and aspiration at 6 months following treatment. On
      subjective evaluation, the V60, the Dmax and the Dmean for SPCM were correlated
      with QoL scores for HNSO at 3 months, whereas the V70 for SPCM were correlated
      with QoL scores for HNPA and the V60, the V65, the V70, the Dmax and the Dmean
      for SPCM were correlated with QoL scores for HNSO at 6 months following
      treatment. CONCLUSIONS: The use of multiple dysphagia-related endpoints to
      complement eachother rather than to overlap with one another, as well as the use
      of multiple evaluations over time to represent a scale of early to late findings
      might provide a better insight in terms of the association of the clinical
      correlates of dysphagia with the dose-volume data for the dysphagia-related
      anatomical structures.

PMID- 24928363
TI  - From the cell of Schwann to schwannoma--a century's fruition.
AB  - The word "schwannoma" is pervasive throughout the neurosurgical community.
      However, little is known about the origin of the cell of "Schwann cell," the
      manifestation of the tumor's nomenclature, or the prominent physicians who
      studied its etiopathogenesis. Schwann was a founding father of cellular theory
      and one of the greatest scientists of the 19th century. He not only proposed cell
      theory but also discovered the "secondary" nerve cell and hypothesized its
      possible function in myelination. It took a century to confirm Schwann's
      hypothesis. In 1954, Geren, aided by the electron microscope, demonstrated that
      the cell of Schwann is responsible for nerve myelination. Concurrently,
      researchers worked to understand the etiology and pathogenesis of peripheral
      nerve neoplasms. Several attempts were made; Older, Virchow, and von
      Recklinghausen were the first pioneers who worked on the classification of these
      neoplasms. However, Masson first used the word "schwannoma" to describe
      peripheral nerve neoplasms other than neuromas. His French colleague Nageotte
      used the term "peripheral-glioma" to denote these tumors. These schwannomas were
      considered to have a malignant course. In 1932, Penfield attempted to classify
      peripheral nerve neoplasms into 3 categories: peripheral fibroblastoma,
      peripheral glioma, and neurofibroma of von Recklinghausen. He classified
      "Verocay's neurinoma," "Masson's schwannoma," and "cerebellopontine angle" tumors
      as perineural fibroblastoma. He believed that these tumors have a non-nerve cell,
      non-Schwann cell origin. He classified the tumors arising from the Schwann cell
      sheath as peripheral gliomas and articulated, "If any tumors are to be called
      schwannomas, these should be." The neurofibroma of von Recklinghausen was
      recognized as a separate entity, as described by von Recklinghausen himself.
      Murray and Stout proposed that schwannomas are essentially benign in nature
      clarifying the abstruseness of the benign or malignant nature of schwannoma. 

PMID- 24928362
TI  - Delayed failure of laser-induced interstitial thermotherapy for postradiosurgery
      brain metastases.

PMID- 24928364
TI  - Above and below: anterior fossa meningioma resection.

PMID- 24928365
TI  - Oral delivery of glucagon like peptide-1 by a recombinant Lactococcus lactis.
AB  - PURPOSE: To develop a live oral delivery system of Glucagon like peptide-1 (GLP
      1), for the treatment of Type-2 Diabetes. METHODS: LL-pUBGLP-1, a recombinant
      Lactococcus lactis (L. lactis)) transformed with a plasmid vector encoding GLP-1
      cDNA was constructed and was used as a delivery system. Secretion of rGLP-1 from
      LL-pUBGLP-1 was characterized by ELISA. The bioactivity of the rGLP-1 was
      examined for its insulinotropic activity on HIT-T15 cells. Transport of rGLP-1
      across MDCK cell monolayer when delivered by LL-pUBGLP-1 was studied. The
      therapeutic effect of LL-pUBGLP-1 after oral administration was investigated in
      ZDF rats. RESULTS: DNA sequencing and ELISA confirmed the successful construction
      of the LL-pUBGLP-1 and secretion of the active form of rGLP-1. In vitro
      insulinotropic studies demonstrated that LL-pUBGLP-1 could significantly (p <
      0.05) stimulate HIT-T15 cells to secrete insulin as compared to the controls.
      When delivered by LL-pUBGLP-1, the GLP-1 transport rate across the MDCK cell
      monolayer was increased by eight times (p < 0.01) as compared to the free
      solution form. Oral administration of LL-pUBGLP-1 in ZDF rats resulted in a
      significant decrease (10-20%, p < 0.05) in blood glucose levels during 2-11 h
      post dosing and a significant increase in insulin AUC0-11h (2.5 times, p < 0.01)
      as compared to the free solution. CONCLUSION: The present study demonstrates that
      L. lactis when genetically modified with a recombinant plasmid can be used for
      the oral delivery of GLP-1.

PMID- 24928366
TI  - Cell-free microfluidic determination of P-glycoprotein interactions with
      substrates and inhibitors.
AB  - The membrane protein P-glycoprotein (P-gp) plays key roles in the oral
      bioavailability of drugs, their blood brain barrier passage as well as in
      multidrug resistance. For new drug candidates it is mandatory to study their
      interaction with P-gp, according to FDA and EMA regulations. The vast majority of
      these tests are performed using confluent cell layers of P-gp overexpressing cell
      lines that render these tests laborious. In this study, we introduce a cell-free
      microfluidic assay for the rapid testing of drug- P-gp interactions. Cell-derived
      vesicles are prepared from MDCKII-MDR1 overexpressing cells and immobilized on
      the surface of a planar microfluidic device. The drug is delivered continuously
      to the vesicles and calcein accumulation is monitored by means of a fluorescence
      assay and total internal reflection fluorescence (TIRF) microscopy. Only small
      amounts of compounds (~10 MUl) are required in concentrations of 5, 25 and 50 MUM
      for a test that provides within 5 min information on the apparent dissociation
      constant of the drug and P-gp. We tested 10 drugs on-chip, 9 of which are
      inhibitors or substrates of P-glycoprotein and one negative control. We
      benchmarked the measured apparent dissociation constants against an alternative
      assay on a plate reader and reference data from FDA. These comparisons revealed
      good correlations between the logarithmic apparent dissociation constants (R(2) =
      0.95 with ATPase assay, R(2) = 0.93 with FDA data) and show the reliability of
      the rapid on-chip test. The herein presented assay has an excellent screening
      window factor (Z'-factor) of 0.8, and is suitable for high-throughput testing. 

PMID- 24928367
TI  - Neuroprotective effects of corn silk maysin via inhibition of H2O2-induced
      apoptotic cell death in SK-N-MC cells.
AB  - AIMS: Neuroprotective effects of maysin, which is a flavone glycoside that was
      isolated from the corn silk (CS, Zea mays L.) of a Korean hybrid corn
      Kwangpyeongok, against oxidative stress (H2O2)-induced apoptotic cell death of
      human neuroblastoma SK-N-MC cells were investigated. MAIN METHODS: Maysin
      cytotoxicity was determined by measuring cell viability using MTT and lactate
      dehydrogenase (LDH) assays. Intracellular reactive oxygen species (ROS) were
      measured using a 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Apoptotic cell
      death was monitored by annexin V-FITC/PI double staining and by a TUNEL assay.
      Antioxidant enzyme mRNA levels were determined by real-time PCR. The cleavage of
      poly (ADP-ribose) polymerase (PARP) was measured by western blotting. KEY
      FINDINGS: Maysin pretreatment reduced the cytotoxic effect of H2O2 on SK-N-MC
      cells, as shown by the increase in cell viability and by reduced LDH release.
      Maysin pretreatment also dose-dependently reduced the intracellular ROS level and
      inhibited PARP cleavage. In addition, DNA damage and H2O2-induced apoptotic cell
      death were significantly attenuated by maysin pretreatment. Moreover, maysin
      pretreatment (5-50 MUg/ml) for 2h significantly and dose-dependently increased
      the mRNA levels of antioxidant enzymes (CAT, GPx-1, SOD-1, SOD-2 and HO-1) in
      H2O2 (200 MUM)-insulted cells. SIGNIFICANCE: These results suggest that CS maysin
      has neuroprotective effects against oxidative stress (H2O2)-induced apoptotic
      death of human brain SK-N-MC cells through its antioxidative action. This report
      is the first regarding neuroprotective health benefits of corn silk maysin by its
      anti-apoptotic action and by triggering the expression of intracellular
      antioxidant enzyme systems in SK-N-MC cells.

PMID- 24928368
TI  - Effects of dietary glucose and fructose upon cannabinoid CB1 receptor
      functionality in the rat brain: a pilot study.
AB  - AIMS: A high consumption of fructose leads not only to peripheral changes in
      insulin sensitivity and vascular function, but also to central changes in several
      brain regions. Given the role of the endogenous cannabinoid system in the control
      of energy intake, we undertook a pilot study to determine whether a high fructose
      diet produced changes in brain CB1 receptor functionality. MAIN METHODS: Male
      rats given access ad libitum to normal chow were given either water, glucose or
      fructose solutions to drink. CB1 receptor functionality was measured
      autoradiographically as the increase in [(35)S]GTPgammaS binding produced by the
      agonist CP55,940. KEY FINDINGS: Seven regions were investigated: the prefrontal
      cortex, caudate-putamen, hippocampal CA1-CA3, dentate gyrus, amygdala, and
      dorsomedial and ventromedial hypothalami. Two-way robust Wilcoxon analyses for
      each brain region indicated that the dietary treatment did not produce
      significant main effects upon agonist-stimulated [(35)S]GTPgammaS binding in any
      of the regions, in contrast to a significant main effect upon both leptin and
      adiponectin levels in the blood. However, a MANCOVA of the data controlling for
      leptin and adiponectin as co-variables identified a significant effect of glucose
      and fructose treatment for five weeks upon the [(35)S]GTPgammaS response in the
      ventromedial hypothalamus, a region of importance for regulation of appetite.
      SIGNIFICANCE: It is concluded from this pilot study that palatable solutions do
      not produce overt changes in brain CB1 receptor functionality, although subtle
      changes in discrete brain regions may occur.

PMID- 24928369
TI  - Medial patellofemoral ligament reconstruction as an isolated or combined
      procedure for recurrent patellar instability.
AB  - PURPOSE: The principal aim of this study was to report the outcomes of medial
      patellofemoral ligament (MPFL) reconstruction, used as either an isolated
      procedure or in combination with another stabilization procedure, for the primary
      treatment of recurrent patellar instability. METHODS: Between 2007 and 2012, 45
      patients with recurrent patellar instability and no prior stabilization surgery
      had an MPFL reconstruction by a single surgeon, either as an isolated procedure
      or in combination with another stabilization procedure. Questionnaires detailing
      patellar instability since surgery, knee pain, ability to negotiate stairs, and
      sports participation were completed, and data regarding examination and
      radiological findings were collected from the medical record. RESULTS: A total of
      36 (80%) patients completed the questionnaire at a mean of 3.1 years (minimum 1
      year), whilst a further 11% had clinical follow-up of greater than 1 year. Four
      patients were excluded due to lack of adequate follow-up. Thirty-one patients had
      an isolated MPFL reconstruction and none had further patellar instability. Of the
      ten patients who had a combined procedure, one experienced recurrent instability.
      Return to sport rates were 81 and 57% for the isolated and combined groups,
      respectively, with the majority returning to strenuous sport (81 and 57%,
      respectively). Most patients (96 and 80%) could negotiate stairs without
      difficulty, whilst 38 and 40% reported some degree of anterior knee pain.
      CONCLUSIONS: This study shows that satisfactory results can be obtained using
      MPFL reconstruction either in isolation or in combination to treat recurrent
      patellar instability. Whether the indications for an isolated MPFL can be
      extended further remains unclear. LEVEL OF EVIDENCE: III.

PMID- 24928370
TI  - Effect of open wedge high tibial osteotomy on the lateral tibiofemoral
      compartment in sheep. Part III: analysis of the microstructure of the subchondral
      bone and correlations with the articular cartilage and meniscus.
AB  - PURPOSE: First, to evaluate whether medial open wedge high tibial osteotomy (HTO)
      induces alterations of the microstructure of the lateral tibial subchondral bone
      plate of sheep. Second, to test the hypothesis that specific correlations exist
      between topographical structural alterations of the subchondral bone, the
      cartilage and the lateral meniscus. METHODS: Three experimental groups received
      biplanar osteotomies of the right proximal tibiae: (a) closing wedge HTO (4.5
      degrees  of tibial varus), (b) opening wedge HTO (4.5 degrees  tibial valgus;
      standard correction) and (c) opening wedge HTO (9.5 degrees  of valgus;
      overcorrection), each of which was compared to the non-osteotomised contralateral
      proximal tibiae. After 6 months, subchondral bone structure indices were measured
      by computed tomography. Correlations between the subchondral bone, the articular
      cartilage and the lateral meniscus were determined. RESULTS: Increased loading by
      valgus overcorrection led to an enlarged specific bone surface (BS/BV) in the
      subarticular spongiosa compared with unloading by varisation. The subchondral
      bone plate was 3.9-fold thicker in the central region of the lateral tibial
      plateau than in the submeniscal periphery. Its thickness in the central region
      significantly correlated with the thickness of the articular cartilage. In the
      submeniscal region, such correlation did not exist. In general, a higher degree
      of osteoarthritis (OA) correlated with alterations of the subchondral bone plate
      microstructure. OA of the submeniscal articular cartilage also correlated with
      worse matrix staining of the lateral meniscus. CONCLUSION: Osteoarthritis changes
      are associated with alterations of the subchondral bone plate microstructure.
      Specific topographical relationships exist in the central region between the
      articular cartilage and subchondral bone plate thickness, and in the submeniscal
      periphery between and the articular cartilage and lateral meniscus. From a
      clinical perspective, the combined follow-up data from this and the previous two
      investigations suggest that open wedge valgus HTO is a safe procedure for the
      lateral compartment to manage medial osteoarthritis of the knee with varus
      malalignment in the short term.

PMID- 24928371
TI  - Cryotherapy on postoperative rehabilitation of joint arthroplasty.
AB  - PURPOSE: The effectiveness of cryotherapy on joint arthroplasty recovery remains
      controversial. This systematic review was conducted to assess the effectiveness
      of cryotherapy in patients after joint arthroplasty. METHODS: Comprehensive
      literature searches of several databases including Cochrane Library (2013),
      MEDLINE (1950-2013), and Embase (1980-2013) were performed. We sought randomised
      controlled trials that compared the experimental group received any form of
      cryotherapy with any control group after joint arthroplasty. The main outcomes
      were postoperative blood loss, adverse events, and pain. Analyses were performed
      with Revman 5.0. Results were shown as mean differences (MD) and standard
      deviations or as risk difference and 95 % confidence intervals (CIs). RESULTS:
      Ten trials comprised 660 total knee arthroplastys and three trials comprised 122
      total hip arthroplastys (THAs) met the inclusion criteria. Blood loss was
      significantly decreased by cryotherapy (MD = -109.68; 95 % CI -210.92 to -8.44; P
      = 0.03). Cryotherapy did not increase the risk of adverse effect (n.s.).
      Cryotherapy decreased pain at the second day of postoperative (MD = -1.32; 95 %
      CI -2.37 to -0.27; P = 0.0003), but did not decreased pain at the first and third
      day of postoperative (n.s.). CONCLUSIONS: Cryotherapy appears effective in these
      selected patients after joint arthroplasty. The benefits of cryotherapy on blood
      loss after joint arthroplasty were obvious. However, the subgroup analysis
      indicated that cryotherapy did not decreased blood loss after THA. Cryotherapy
      did not increase the risk of adverse effect. Cryotherapy decreased pain at the
      second day of postoperative, but did not decreased pain at the first and third
      day of postoperative. LEVEL OF EVIDENCE: II.

PMID- 24928372
TI  - [Laparoscopic surgery for colon cancer: quality requirements for (extended) right
      hemicolectomy].
AB  - The current S3 guidelines on the surgical treatment of colorectal cancer note
      that with a suitable patient selection and expertise of the surgeon the same
      oncological results can be achieved laparoscopically as with the open procedure.
      This requires that the same quality requirements have to be provided for both
      methods. The most important quality parameters of right sided (extended)
      hemicolectomy are central ligation of the supplying arteries (ileocolic artery,
      right branch of the middle colic artery and middle colic artery) flush to the
      central origin of the vessel (superior mesenteric artery or middle colic artery)
      and the sharp dissection of the mesocolon without any preparation tears. The
      photographic documentation of the fresh surgical specimens for categorizing the
      preparation quality as well as to determine the pedicle of the vessel can capture
      this quality well and is also currently the best surrogate parameter to evaluate
      the oncological quality of the operation. At present, there are still
      considerable widespread deficits not only with the laparoscopic approach but also
      in open surgery which must be urgently fixed. 

PMID- 24928373
TI  - Factors associated with in utero demise of fetuses that have underlying cardiac
      pathologies.
AB  - Factors associated with in utero fetal demise (IUFD) of fetuses that have
      underlying cardiac pathologies are largely unknown. This case-control study aimed
      to define the prevalence of IUFD in fetuses with a diagnosis of cardiac
      pathologies and to identify prenatal predictors of IUFD. Between January 2004 and
      December 2010, 74 IUFD cases [4.6 %; 95 % confidence interval (CI) 3.7-5.8 %]
      were identified from 1,584 cases with a diagnosis of structural or functional
      cardiac lesions in the Hospital for Sick Children database. The cases were
      divided into right-sided (N = 28), left-sided (N = 23), great artery (N = 8), and
      miscellaneous (N = 15) groups. The control subjects (1:1 ratio) were fetuses that
      had cardiac pathology diagnosed within 48 h of the IUFD case. Multivariable
      regression models were used to determine echocardiographic predictors of IUFD.
      The prevalence of IUFD was greatest in hypertrophic cardiomyopathy (8/16, 50 %)
      and Ebstein's anomaly/tricuspid dysplasia (4/15, 27 %) and lowest in
      transposition of the great arteries (2/85, 1 %). The findings showed IUFD to be
      associated with hydrops in 17 (23 %) of the 74 cases and arrhythmia in 11 (15 %)
      of the 74 cases. The factors identified by univariable logistic regression
      analyses were right ventricular dysfunction [odds ratio (OR) 2.7; p = 0.001],
      left ventricular dysfunction (OR 1.8; p = 0.007), umbilical vein pulsations (OR
      10.9; p = 0.002), and abnormal ductus venosus flow (OR 3.3; p = 0.01). The
      factors associated with IUFD in multivariable logistic regression models were
      cardiomegaly (OR 5.6; p = 0.01), hydrops (OR 29.5; p = 0.001), pericardial
      effusion (OR 4.1; p = 0.06), and extracardiac abnormalities (OR 7.2; p < 0.001).
      The prevalence of IUFD is greatest in conditions affecting the ventricular
      myocardium. The onset of IUFD appears to be related initially to right
      ventricular dysfunction. Closer surveillance is recommended for lesions at risk
      of IUFD.

PMID- 24928374
TI  - Changes in the transcriptional profile in response to overexpression of the
      osteopontin-c splice isoform in ovarian (OvCar-3) and prostate (PC-3) cancer cell
      lines.
AB  - BACKGROUND: Especially in human tumor cells, the osteopontin (OPN) primary
      transcript is subject to alternative splicing, generating three isoforms termed
      OPNa, OPNb and OPNc. We previously demonstrated that the OPNc splice variant
      activates several aspects of the progression of ovarian and prostate cancers. The
      goal of the present study was to develop cell line models to determine the impact
      of OPNc overexpression on main cancer signaling pathways and thus obtain insights
      into the mechanisms of OPNc pro-tumorigenic roles. METHODS: Human ovarian and
      prostate cancer cell lines, OvCar-3 and PC-3 cells, respectively, were stably
      transfected to overexpress OPNc. Transcriptomic profiling was performed on these
      cells and compared to controls, to identify OPNc overexpression-dependent changes
      in gene expression levels and pathways by qRT-PCR analyses. RESULTS: Among 84
      genes tested by using a multiplex real-time PCR Cancer Pathway Array approach, 34
      and 16, respectively, were differentially expressed between OvCar-3 and PC-3 OPNc
      overexpressing cells in relation to control clones. Differentially expressed
      genes are included in all main hallmarks of cancer, and several interacting
      proteins have been identified using an interactome network analysis. Based on
      marked up-regulation of Vegfa transcript in response to OPNc overexpression, we
      partially validated the array data by demonstrating that conditioned medium (CM)
      secreted from OvCar-3 and PC-3 OPNc-overexpressing cells significantly induced
      endothelial cell adhesion, proliferation and migration, compared to CM secreted
      from control cells. CONCLUSIONS: Overall, the present study elucidated
      transcriptional changes of OvCar-3 and PC-3 cancer cell lines in response to OPNc
      overexpression, which provides an assessment for predicting the molecular
      mechanisms by which this splice variant promotes tumor progression features.

PMID- 24928375
TI  - Predictors of short-term recovery of urinary continence after radical
      prostatectomy.
AB  - PURPOSE: To evaluate treatment variables for early urinary continence status 6
      weeks following radical prostatectomy. METHODS: In this retrospective analysis,
      4,028 consecutive patients underwent open radical retropubic (RRP) or robot
      assisted transperitoneal prostatectomy (RARP) at a single academic institution
      (07/2003-07/2013). After discharge, patients were offered 3-week treatment in a
      rehabilitation facility. Patients who opted for rehabilitation (n = 2,998, 74.4%)
      represent our study cohort. Exclusion criteria were acute urinary retention after
      catheter removal (n = 55, 1.4%), incomplete datasets (n = 50, 1.2%) or refusal of
      rehabilitation (n = 925, 23.0%). Results of urinary continence were evaluated
      from final rehabilitation reports. Twenty-two clinical and oncological variables
      were statistically analysed in uni- and multivariable analyses to determine
      whether they were associated with early urinary continence status six weeks after
      radical prostatectomy. Odds ratios and 95% CI as well as p values were
      calculated. A p level of 0.05 was considered as significant. RESULTS: Six weeks
      after surgery, 1,962 (65.4%) patients were continent (<=1 pad/day) and 1,036
      (34.6%) patients were considered incontinent. Age, clinical stage, PSA, ASA
      score, prior TURP, seminal vesicle invasion, Gleason score, nerve-sparing status,
      intraoperative blood loss, catheterisation time, OR time, surgical caseload
      >1,000 and the surgeon were associated with continence status on univariable
      analysis (p < 0.05). On multivariable analysis, nerve-sparing procedure (NS),
      clinical stage, individual surgeon, patient age, surgical procedure (RARP vs.
      RRP) and duration of catheterisation were independent predictors (p < 0.05) of
      incontinence status. CONCLUSIONS: Strategies that can ensure NS procedures and
      early catheter removal should be applied to enable early recovery of urinary
      continence.

PMID- 24928376
TI  - Effects of quercetin on hedgehog signaling in chronic myeloid leukemia KBM7
      cells.
AB  - OBJECTIVE: To investigate the effects of quercetin on Hedgehog (Hh) signaling in
      chronic myeloid leukemia KBM7 cells. METHODS: The KBM7 cells were treated with
      50, 100 and 200 MUmol/L quercetin for 48 h respectively. And then the trypan blue
      assay was used to examine the proliferative inhibition of quercetin. Apoptotic
      cells and cell cycle were measured by flow cytometry. The mRNA and protein
      expression were detected by quantitative real-time polymerase chain reaction
      (PCR) and Western blot, respectively. RESULTS: Quercetin significantly inhibited
      KBM7 cell proliferation, induced cell apoptosis, and blocked cell cycle at G1
      phase, which were in dose-dependent manners. The mRNA and protein expression of
      Smoothened and Glioma1 (Gli1), the members of Hh pathway decreased after
      treatment with quercetin. The Bcl-2 and Cyclin D1, targets of Hh signaling, also
      decreased after treatment with quercetin, respectively. Quercetin also could
      increase p53 and Caspase-3 expression. Bcr-abl mRNA copies decreased, but no
      changes of phosphorylated Bcr-abl and Bcr-abl proteins were observed, after
      treatment with quercetin. CONCLUSION: Quercetin could inhibit Hh signaling and
      its downstream targets in the KBM7 cells. And it might be one of mechanisms of
      inducing apoptosis and inhibiting cell cycle by quercetin.

PMID- 24928377
TI  - Effects of acupuncture on the tissue distribution of Paclitaxel in lung carcinoma
      mice.
AB  - OBJECTIVE: To study whether acupuncture affects the tissue distribution of
      Paclitaxel in mouse lung carcinoma. METHODS: Totally 90 mice were divided into
      Paclitaxel group, Paclitaxel + Feishu (BL13) group, and Paclitaxel + Lingtai
      (DU10) group. Each group was consisted of 30 mice. After Paclitaxel injection,
      the mice received electro-acupuncture at Feishu or Lingtai acupoints once a day
      for 8 days. The effect of acupuncture on the tissue distribution of Paclitaxel
      was evaluated using high-performance liquid chromatography at 1, 2, and 3 h,
      respectively. The lung, liver, spleen, and kidney were examined for the
      concentration of Paclitaxel seperately. RESULTS: Paclitaxel was widely
      distributed in various organs, particularly in the lung, liver, and kidney.
      Acupuncture at Lingtai or Feishu acupoints resulted in an obvious decrease of
      Paclitaxel distribution in kidney and delayed Paclitaxel distribution in liver.
      Meanwhile, it increased the time of metabolism. Acupuncture at Feishu acupoint
      facilitated the delivery of Paclitaxel to lung more effectively than did
      acupuncture at Lingtai acupoint. CONCLUSIONS: Applying acupuncture at particular
      acupoints can influence tissue distribution of Paclitaxel. Tissue distribution
      change might be one of the mechanisms of acupuncture treatment during
      chemotherapy.

PMID- 24928378
TI  - Photocatalytic degradation of molinate in aqueous solutions.
AB  - In this study, the degradation of molinate through heterogeneous photocatalysis,
      using two different types of the semiconductor TiO2 as photocatalyst, as well as
      through homogeneous treatment, applying the photo-Fenton reaction, has been
      investigated. As far as heterogeneous photocatalysis is concerned, the
      degradation of the pesticide follows apparent first-order kinetics, while the
      type of the catalyst and the pH value of the solution affect the degradation
      rate. The effect of the addition of electron scavengers (H2O2 and K2S2O8) was
      also studied. In the case of photo-Fenton-assisted system, the degradation also
      follows pseudo-first-order kinetics. Parameters such as iron's and electron
      scavenger's concentration and inorganic ions strongly affect the degradation
      rate. The extent of pesticide mineralization was investigated using dissolved
      organic carbon (DOC) measurements. The toxicity of the treated solution was
      evaluated using the Microtox test based on the luminescent bacteria Vibrio
      fischeri. The detoxification and mineralization efficiency was found to be
      dependent on the system studied, and although it did not follow the rate of
      pesticide disappearance, it took place in considerable extent. The study of the
      photodegradation treatment was completed by the determination of the intermediate
      by-products formed during the process, which was carried out using LC-MS/MS
      technique and led to similar compounds with both processes.

PMID- 24928379
TI  - A reactive transport model for mercury fate in soil--application to different
      anthropogenic pollution sources.
AB  - Soil systems are a common receptor of anthropogenic mercury (Hg) contamination.
      Soils play an important role in the containment or dispersion of pollution to
      surface water, groundwater or the atmosphere. A one-dimensional model for
      simulating Hg fate and transport for variably saturated and transient flow
      conditions is presented. The model is developed using the HP1 code, which couples
      HYDRUS-1D for the water flow and solute transport to PHREEQC for geochemical
      reactions. The main processes included are Hg aqueous speciation and
      complexation, sorption to soil organic matter, dissolution of cinnabar and liquid
      Hg, and Hg reduction and volatilization. Processes such as atmospheric wet and
      dry deposition, vegetation litter fall and uptake are neglected because they are
      less relevant in the case of high Hg concentrations resulting from anthropogenic
      activities. A test case is presented, assuming a hypothetical sandy soil profile
      and a simulation time frame of 50 years of daily atmospheric inputs. Mercury fate
      and transport are simulated for three different sources of Hg (cinnabar, residual
      liquid mercury or aqueous mercuric chloride), as well as for combinations of
      these sources. Results are presented and discussed with focus on Hg
      volatilization to the atmosphere, Hg leaching at the bottom of the soil profile
      and the remaining Hg in or below the initially contaminated soil layer. In the
      test case, Hg volatilization was negligible because the reduction of Hg(2+) to
      Hg(0) was inhibited by the low concentration of dissolved Hg. Hg leaching was
      mainly caused by complexation of Hg(2+) with thiol groups of dissolved organic
      matter, because in the geochemical model used, this reaction only had a higher
      equilibrium constant than the sorption reactions. Immobilization of Hg in the
      initially polluted horizon was enhanced by Hg(2+) sorption onto humic and fulvic
      acids (which are more abundant than thiols). Potential benefits of the model for
      risk management and remediation of contaminated sites are discussed.

PMID- 24928380
TI  - Influence of operating conditions on nitrous oxide formation during nitritation
      and nitrification.
AB  - Nitrous oxide (N2O), a strong greenhouse gas, can be produced by ammonium
      oxidizing bacteria (AOB) as a by-product of ammonium oxidation and can
      potentially be formed in all types of nitrification processes. However, partial
      nitritation has been reported to cause significantly higher N2O emissions than
      complete nitrification. In the study presented here, the mechanisms and factors
      that drive N2O formation by AOB were investigated with respect to different
      operational strategies to achieve nitrite accumulation base on combined
      evaluation of oxygen uptake rate (OUR) and N2O formation rate. On the one hand,
      N2O formation during partial nitritation and nitrification in a continuously
      stirred tank reactor (CSTR) with continuous aerobic conditions was observed. On
      the other hand, the effect of intermittent aeration on N2O formation during
      nitrification was investigated. The presence of nitrite, the extend of sludge
      specific ammonium loading, low oxygen concentration, and transition from aerobic
      to anoxic conditions significantly increased N2O formation in this reactor
      independently from each other, indicating that different formation pathways,
      supposedly via nitrite or hydroxylamine, were active. 

PMID- 24928381
TI  - Toxicity of atrazine and its bioaccumulation and biodegradation in a green
      microalga, Chlamydomonas mexicana.
AB  - This study evaluated the toxicity of herbicide atrazine, along with its
      bioaccumulation and biodegradation in the green microalga Chlamydomonas mexicana.
      At low concentration (10 MUg L(-1)), atrazine had no profound effect on the
      microalga, while higher concentrations (25, 50, and 100 MUg L(-1)) imposed
      toxicity, leading to inhibition of cell growth and chlorophyll a accumulation by
      22 %, 33 %, and 36 %, and 13 %, 24 %, and 27 %, respectively. Atrazine 96-h EC50
      for C. mexicana was estimated to be 33 MUg L(-1). Microalga showed a capability
      to accumulate atrazine in the cell and to biodegrade the cell-accumulated
      atrazine resulting in 14-36 % atrazine degradation at 10-100 MUg L(-1).
      Increasing atrazine concentration decreased the total fatty acids (from 102 to 75
      mg g(-1)) and increased the unsaturated fatty acid content in the microalga.
      Carbohydrate content increased gradually with the increase in atrazine
      concentration up to 15 %. This study shows that C. mexicana has the capability to
      degrade atrazine and can be employed for the remediation of atrazine-contaminated
      streams.

PMID- 24928382
TI  - Enhancing soluble phosphorus removal within buffer strips using industrial by
      products.
AB  - Using industrial by-products (IBPs) in conjunction with buffer strips provides a
      potentially new strategy for enhancing soluble phosphorus (P) removal from
      agricultural runoff. Here, we investigate the feasibility of this approach by
      assessing the P sorption properties of IBPs at different solution-IBPs contact
      time (1-120 min) and solution pH (3, 5.5, 7.5), as well as possible adverse
      environmental effects including P desorption or heavy metal mobilisation from
      IBPs. Batch experiments were carried out on two widely available IBPs in the UK
      that demonstrated high P sorption capacity but different physicochemical
      characteristics, specifically ochre and Aluminium (Al) based water treatment
      residuals (Al-WTR). A series of kinetic sorption-desorption experiments alongside
      kinetic modelling were used to understand the rate and the mechanisms of P
      removal across a range of reaction times. The results of the kinetic experiments
      indicated that P was initially sorbed rapidly to both ochre and Al-WTR, followed
      by a second phase characterised by a slower sorption rate. The excellent fits of
      kinetic sorption data to a pseudo-second order model for both materials suggested
      surface chemisorption as the rate-controlling mechanism. Neither ochre nor Al-WTR
      released substantial quantities of either P or heavy metals into solution,
      suggesting that they could be applied to buffer strip soils at recommended rates
      (<=30 g kg(-1) soil) without adverse environmental impact. Although the rate of P
      sorption by freshly-generated Al-WTR applied to buffer strips reduced following
      air-drying, this would not limit its practical application to buffer strips in
      the field if adequate contact time with runoff was provided.

PMID- 24928383
TI  - Turning waste into valuable resource: potential of electric arc furnace dust as
      photocatalytic material.
AB  - This paper explores the potential of a hazardous waste of difficult management,
      electric arc furnace dust (EAFD), as photocatalytic material. Starting from a
      real waste coming from a Spanish steel factory, chemical, mineralogical, and
      optical characterizations have been carried out. Direct trials on EAFD and mortar
      containing this waste have been performed to evaluate its potential as
      photocatalyst itself and within a cementitious material. The analysis of
      photocatalytic properties has been done by two different methods: degradation of
      NO x and degradation of rhodamine (RhB). As a result, it can be said that EAFD
      exhibited photocatalytic activity for both configurations with UV and visible
      light, having the mortar enhanced photocatalytic activity for NO x with respect
      to the EAFD itself. Additionally, in direct trials on the EAFD, it has been able
      to degrade RhB even in the dark, which has been attributed to transfer of
      electrons between the adsorbed RhB and the conduction band of some oxides in the
      dust.

PMID- 24928384
TI  - Response to the authors of the article "Enhanced recovery after scheduled colo
      rectal surgery" published in the Journal de Chirurgie.

PMID- 24928385
TI  - Mitofusin 2 decreases intracellular lipids in macrophages by regulating
      peroxisome proliferator-activated receptor-gamma.
AB  - Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying
      mechanism remains elusive. This study aims to reveal how Mfn2 functions in the
      atherosclerosis. Mfn2 expression was found to be significantly reduced in
      arterial atherosclerotic lesions of both mice and human compared with healthy
      counterparts. Here, we observed that Mfn2 increased cellular cholesterol
      transporter expression in macrophages by upregulating peroxisome proliferator
      activated receptor-gamma, an effect achieved at least partially by inhibiting
      extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated
      protein kinases (MAPKs) pathway. These findings provide insights into potential
      mechanisms of Mfn2-mediated alterations in cholesterol transporter expression,
      which may have significant implications for the treatment of atherosclerotic
      heart disease. 

PMID- 24928386
TI  - An automated mass spectrometry-based screening method for analysis of sulfated
      glycosaminoglycans.
AB  - Glycosaminoglycans (GAGs) are linear polysaccharides, consisting of repeated
      disaccharide units, attached to core proteins in all multicellular organisms.
      Chondroitin sulfate (CS) and dermatan sulfate (DS) constitute a subgroup of
      sulfated GAGs for which the degree of sulfation varies between species and
      tissues. One major goal in GAG characterization is to correlate structure to
      function. A common approach is to exhaustively degrade the GAG chains and
      thereafter determine the amount of component disaccharide units. In large-scale
      studies, there is a need for high-throughput screening methods since existing
      methods are either very time- or samples consuming. Here, we present a new
      strategy applying MALDI-TOF MS in positive ion mode for semi-qualitative and
      quantitative analysis of CS/DS derived disaccharide units. Only a few picomoles
      of sample are required per analysis and 10 samples can be analyzed in 25 min,
      which makes this approach an attractive alternative to many established assay
      methods. The total CS/DS concentration in 19 samples derived from Caenorhabditis
      elegans and mammalian tissues and cells was determined. The obtained results were
      well in accordance with concentrations determined by a standard liquid
      chromatography-based method, demonstrating the applicability of the method for
      samples from various biological matrices containing CS/DS of different sulfation
      degrees.

PMID- 24928387
TI  - Secreted meningeal chemokines, but not VEGFA, modulate the migratory properties
      of medulloblastoma cells.
AB  - Leptomeningeal metastasis is a cause of morbidity and mortality in
      medulloblastoma, but the understanding of molecular mechanisms driving this
      process is nascent. In this study, we examined the secretory chemokine profile of
      medulloblastoma cells (DAOY) and a meningothelial cell line (BMEN1). Conditioned
      media (CM) of meningothelial cells increased adhesion, spreading and migration of
      medulloblastoma. VEGFA was identified at elevated levels in the CM from BMEN1
      cells (as compared to DAOY CM); however, recombinant VEGFA alone was insufficient
      to enhance medulloblastoma cell migration. In addition, bevacizumab, the VEGFA
      scavenging monoclonal antibody, did not block the migratory phenotype induced by
      the CM. These results reveal that paracrine factors secreted by meningothelial
      cells can influence migration and adherence of medulloblastoma tumor cells, but
      VEGFA may not be a specific target for therapeutic intervention in this context. 

PMID- 24928388
TI  - Non-viral reprogramming of fibroblasts into induced pluripotent stem cells by
      Sleeping Beauty and piggyBac transposons.
AB  - The generation of induced pluripotent stem (iPS) cells represents a promising
      approach for innovative cell therapies. The original method requires viral
      transduction of several reprogramming factors, which may be associated with an
      increased risk of tumorigenicity. Transposition of reprogramming cassettes
      represents a recent alternative to viral approaches. Since binary transposons can
      be produced as common plasmids they provide a safe and cost-efficient alternative
      to viral delivery methods. Here, we compared the efficiency of two different
      transposon systems, Sleeping Beauty (SB) and piggyBac (PB), for the generation of
      murine iPS. Murine fibroblasts derived from an inbred BL/6 mouse line carrying a
      pluripotency reporter, Oct4-EGFP, and fibroblasts derived from outbred NMRI mice
      were employed for reprogramming. Both transposon systems resulted in the
      successful isolation of murine iPS cell lines. The reduction of the core
      reprogramming factors to omit the proto-oncogene c-Myc was compatible with iPS
      cell line derivation, albeit with reduced reprogramming efficiencies. The
      transposon-derived iPS cells featured typical hallmarks of pluripotency,
      including teratoma growth in immunodeficient mice. Thus SB and PB transposons
      represent a promising non-viral approach for iPS cell derivation. 

PMID- 24928389
TI  - Functional proteomics revealed IL-1beta amplifies TNF downstream protein signals
      in human synoviocytes in a TNF-independent manner.
AB  - IL-1beta is readily detectable in numerous joint inflammations. It can change the
      transcriptomic signature of fibroblast-like synoviocytes (FLS) of arthritis
      toward promoting migration and invasion that are relevant to arthritis
      progression. We hypothesize that IL-1beta partially contributes to the onset of
      osteoarthritis (OA). We compared the tissue samples from OA and fracture subjects
      and found that IL-1beta expression was significantly higher in the OA synovium,
      while TNF-alpha expression showed no significance. We demonstrated that IL-1beta
      significantly increases the IL-6 and IL-8 secretions of human normal FLS;
      however, IL-1beta does not induce TNF secretion. With metabolic labeling based
      proteomics and pathway analysis, we found that IL-1beta significantly increases
      the TNF downstream protein expression in FLS even with complete absence of TNF
      and/or blocking of the NF-kappaB pathway. Among these proteins, we verified that
      p62 can differentiate the OA from fracture synovitis. In conclusion, we
      demonstrated that IL-1beta can amplify the TNF downstream protein signals in
      human synoviocytes in a TNF-independent manner; in addition, p62 is a potential
      FLS biomarker for synovitis. 

PMID- 24928390
TI  - IKK regulates the deubiquitinase CYLD at the postsynaptic density.
AB  - K63-linked polyubiquitination of proteins regulates their trafficking into
      specific cellular pathways such as endocytosis and autophagy. CYLD, a
      deubiquitinase specific for K63-linked polyubiquitins, is present in high
      quantities at the postsynaptic density (PSD). It was previously shown that, under
      excitatory conditions, CaMKII activates CYLD in a Ca(2+)-dependent manner. The
      observation that CYLD can also be phosphorylated in the absence of Ca(2+) in
      isolated PSDs led us to further explore the regulation of CYLD under basal
      conditions. A possible involvement of the autonomous form of CaMKII and IKK, both
      kinases known to be localized at the PSD, was examined. A CaMKII inhibitor CN21
      had no effect on CYLD phosphorylation in the absence of Ca(2+), but two different
      IKK inhibitors, IKK16 and tatNEMO, inhibited its phosphorylation. Immuno-electron
      microscopy on hippocampal cultures, using an antibody for CYLD phosphorylated at
      S-418, revealed that the phosphorylated form of CYLD is present at the PSD under
      basal conditions. Phosphorylation of CYLD under basal conditions was inhibited by
      IKK16. NMDA treatment further promoted phosphorylation of CYLD at the PSD, but
      IKK16 failed to block the NMDA-induced effect. In vitro experiments using
      purified proteins demonstrated direct phosphorylation and activation of CYLD by
      the beta catalytic subunit of IKK. Activation of IKK in isolated PSDs also
      promoted phosphorylation of CYLD and an increase in endogenous deubiquitinase
      activity for K63-linked polyubiquitins. Altogether, the results suggest that in
      the absence of excitatory conditions, constitutive IKK activity at the PSD
      regulates CYLD and maintains basal levels of K63-linkage specific
      deubiquitination at the synapse. 

PMID- 24928391
TI  - Vascular endothelial cells promote cortical neurite outgrowth via an integrin
      beta3-dependent mechanism.
AB  - The interaction of neurons with their non-neuronal milieu plays a crucial role in
      the formation of neural networks, and wide variety of cell-contact-dependent
      signals that promote neurite elongation have been identified. In this study, we
      found that vascular endothelial cells promote neurite elongation in an integrin
      beta3-dependent manner. Vascular endothelial cells from the cerebral cortex
      promoted neurite elongation of cortical neurons in a cell contact-dependent
      manner. This effect was mediated by arginine-glycine-aspartic acid (RGD), a major
      recognition sequence for integrins. Pharmacological blockade of integrin beta3
      abolished the neurite elongation effect induced by the endothelial cells.
      Immunocytochemical analysis revealed that integrin beta3 was expressed on
      cultured cortical neurons. These results demonstrate that the neurite elongation
      promoted by vascular endothelial cells requires integrin beta3. Vascular
      endothelial cells may therefore play a role in the development and repair of
      neural networks in the central nervous system. 

PMID- 24928392
TI  - A PerR-like protein involved in response to oxidative stress in the extreme
      bacterium Deinococcus radiodurans.
AB  - Response and defense systems against reactive oxygen species (ROS) contribute to
      the remarkable resistance of Deinococcus radiodurans to oxidative stress induced
      by oxidants or radiation. However, mechanisms involved in ROS response and
      defense systems of D. radiodurans are not well understood. Fur family proteins
      are important in ROS response. Only a single Fur homolog is predicted by sequence
      similarity in the current D. radiodurans genome database. Our bioinformatics
      analysis demonstrated an additional guanine nucleotide in the genome of D.
      radiodurans that is not in the database, leading to the discovery of another Fur
      homolog DrPerR. Gene disruption mutant of DrPerR showed enhanced resistance to
      hydrogen peroxide (H2O2) and increased catalase activity in cell extracts. Real
      time PCR results indicated that DrPerR functions as a repressor of the catalase
      gene katE. Meanwhile, derepression of dps (DNA-binding proteins from starved
      cells) gene under H2O2 stress by DrPerR point to its regulatory role in metal
      ions hemostasis. Thus, DrPerR might function as a Fur homolog protein which is
      involved in ROS response and defense. These results help clarify the complicated
      regulatory network that responds to ROS stress in D. radiodurans. 

PMID- 24928393
TI  - Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a
      zebrafish model.
AB  - Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel member of the M1
      family of zinc metallopeptidases, which has been reported to play a crucial role
      in angiogenesis. In the present study, we conducted a target-based screening of
      natural products and synthetic chemical libraries using the purified enzyme to
      search novel inhibitors of A-LAP. Amongst several hits isolated, a natural
      product purpurin was identified as one of the most potent inhibitors of A-LAP
      from the screening. In vitro enzymatic analyses demonstrated that purpurin
      inhibited A-LAP activity in a non-competitive manner with a Ki value of 20 M. In
      addition, purpurin showed a strong selectivity toward A-LAP versus another member
      of M1 family of zinc metallopeptidase, aminopeptidase N (APN). In angiogenesis
      assays, purpurin inhibited the vascular endothelial growth factor (VEGF)-induced
      invasion and tube formation of human umbilical vein endothelial cells (HUVEC).
      Moreover, purpurin inhibited in vivo angiogenesis in zebrafish embryo without
      toxicity. These data demonstrate that purpurin is a novel specific inhibitor of A
      LAP and could be developed as a new anti-angiogenic agent.

PMID- 24928394
TI  - A heterocyclic molecule kartogenin induces collagen synthesis of human dermal
      fibroblasts by activating the smad4/smad5 pathway.
AB  - Declined production of collagen by fibroblasts is one of the major causes of
      aging appearance. However, only few of compounds found in cosmetic products are
      able to directly increase collagen synthesis. A novel small heterocyclic compound
      called kartogenin (KGN) was found to stimulate collagen synthesis of mesenchymal
      stem cells (MSCs). So, we hypothesized and tested that if KGN could be applied to
      stimulate the collagen synthesis of fibroblasts. Human dermal fibroblasts in
      vitro were treated with various concentrations of KGN, with dimethyl sulfoxide
      (DMSO) serving as the negative control. Real-time reverse-transcription
      polymerase chain reaction, Western blot, and immunofluorescence analyses were
      performed to examine the expression of collagen and transforming growth factor
      beta (TGF-beta) signaling pathway. The production of collagen was also tested in
      vivo by Masson's trichrome stain and immunohistochemistry in the dermis of mice
      administrated with KGN. Results showed that without obvious influence on
      fibroblasts' apoptosis and viability, KGN stimulated type-I collagen synthesis of
      fibroblasts at the mRNA and protein levels in a time-dependent manner, but KGN
      did not induce expression of alpha-skeletal muscle actin (alpha-sma) or matrix
      metallopeptidase1 (MMP1), MMP9 in vitro. Smad4/smad5 of the TGF-beta signaling
      pathway was activated by KGN while MAPK signaling pathway remained unchanged. KGN
      also increased type-I collagen synthesis in the dermis of BALB/C mice. Our
      results indicated that KGN promoted the type-I collagen synthesis of dermal
      fibroblasts in vitro and in the dermis of mice through activation of the
      smad4/smad5 pathway. This molecule could be used in wound healing, tissue
      engineering of fibroblasts, or aesthetic and reconstructive procedures. 

PMID- 24928395
TI  - Adipogenesis stimulates the nuclear localization of EWS with an increase in its O
      GlcNAc glycosylation in 3T3-L1 cells.
AB  - Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and
      cytosol and is associated with the cell membrane, the regulatory mechanisms of
      its subcellular localization are still unclear. Here we found that adipogenic
      stimuli induce the nuclear localization of EWS in 3T3-L1 cells. Tyrosine
      phosphorylation in the C-terminal PY-nuclear localization signal of EWS was
      negative throughout adipogenesis. Instead, an adipogenesis-dependent increase in
      O-linked beta-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed.
      Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear
      localization of EWS. Our findings suggest that the nuclear localization of EWS is
      partly regulated by the glycosylation. 

PMID- 24928396
TI  - Activation of activin type IB receptor signals in pancreatic beta cells leads to
      defective insulin secretion through the attenuation of ATP-sensitive K+ channel
      activity.
AB  - In studies of gene-ablated mice, activin signaling through activin type IIB
      receptors (ActRIIB) and Smad2 has been shown to regulate not only pancreatic beta
      cell mass but also insulin secretion. However, it still remains unclear whether
      gain of function of activin signaling is involved in the modulation of pancreatic
      beta cell mass and insulin secretion. To identify distinct roles of activin
      signaling in pancreatic beta cells, the Cre-loxP system was used to activate
      signaling through activin type IB receptor (ActRIB) in pancreatic beta cells. The
      resultant mice (pancreatic beta cell-specific ActRIB transgenic (Tg) mice;
      ActRIBCAbetaTg) exhibited a defect in glucose-stimulated insulin secretion (GSIS)
      and a progressive impairment of glucose tolerance. Patch-clamp techniques
      revealed that the activity of ATP-sensitive K(+) channels (KATP channels) was
      decreased in mutant beta cells. These results indicate that an appropriate level
      of activin signaling may be required for GSIS in pancreatic beta cells, and that
      activin signaling involves modulation of KATP channel activity. 

PMID- 24928397
TI  - Structure and regulatory targets of SCO3201, a highly promiscuous TetR-like
      regulator of Streptomyces coelicolor M145.
AB  - SCO3201, a regulator of the TetR family, is a strong repressor of both
      morphological differentiation and antibiotic production when overexpressed in
      Streptomyces coelicolor. Here, we report the identification of 14 novel putative
      regulatory targets of this regulator using in vitro formaldehyde cross-linking.
      Direct binding of purified His6-SCO3201 was demonstrated for the promoter regions
      of 5 regulators (SCO1716, SCO1950, SCO3367, SCO4009 and SCO5046), a putative
      histidine phosphatase (SCO1809), an acetyltransferase (SCO0988) and the
      polyketide synthase RedX (SCO5878), using EMSA. Reverse transcriptional analysis
      demonstrated that the expression of the transcriptional regulators SCO1950,
      SCO4009, SCO5046, as well as of SCO0988 and RedX was down regulated, upon SCO3201
      overexpression, whereas the expression of SCO1809 and SCO3367 was up regulated. A
      consensus binding motif was derived via alignment of the promoter regions of the
      genes negatively regulated. The positions of the predicted operator sites were
      consistent with a direct repressive effect of SCO3201 on 5 out of 7 of these
      promoters. Furthermore, the 2.1A crystal structure of SCO3201 was solved, which
      provides a possible explanation for the high promiscuity of this regulator that
      might account for its dramatic effect on the differentiation process of S.
      coelicolor. 

PMID- 24928398
TI  - Discovery of alkoxyl biphenyl derivatives bearing dibenzo[c,e]azepine scaffold as
      potential dual inhibitors of P-glycoprotein and breast cancer resistance protein.
AB  - We recently reported alkoxyl biphenyl derivatives bearing dibenzo[c,e]azepine
      scaffold as novel P-glycoprotein (P-gp, ABCB1) inhibitors. In this study, their
      ability to reverse breast cancer resistance protein (BCRP, ABCG2)-mediated
      multidrug resistance was tested in HEK293/BCRP cells which was BCRP-transfected
      stable HEK293 cells. It was observed that compounds 4d, 4h, 4i increased
      mitoxantrone accumulation in HEK293/BCRP cells via inhibiting BCRP efflux
      function. Notably, the inhibitory activity of 4i was comparable to that of the
      classical BCRP inhibitor Ko143 at an equimolar concentration. Interestingly, 4i
      had little inhibitory effect on multidrug resistance-associated protein 1 (MRP1,
      ABCC1), another drug efflux transporter. These results, together with the
      previous findings, suggest that 4i may be a dual inhibitor of P-gp and BCRP to
      warrant further investigation. 

PMID- 24928399
TI  - Synthesis and antiproliferative activity of aromatic and aliphatic
      bis[aminomethylidene(bisphosphonic)] acids.
AB  - A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was
      synthesized in the reaction of triethylphosphite with isonitriles followed by
      hydrolysis or dealkylation. The in vitro anti-proliferative effect of all
      synthesized tetraphosphonic acids against MCF-7 breast cancer cells, J774E
      macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic
      derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative
      activity than zoledronic acid. 

PMID- 24928400
TI  - Structure-activity relationships of oxysterol-derived pharmacological chaperones
      for Niemann-Pick type C1 protein.
AB  - Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major
      cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal
      polytopic membrane protein required for intracellular cholesterol trafficking.
      One prevalent mutation (I1061T) has been shown to cause a folding defect, which
      results in failure of endosomal localization of the protein, leading to loss-of
      function phenotype. We have previously demonstrated that several oxysterols and
      their derivatives act as pharmacological chaperones; binding of these compounds
      to NPC1(I1061T) mutant protein corrects the localization/maturation defect of the
      mutant protein. Here, we disclose detailed structure-activity relationships of
      oxysterol derivatives as pharmacological chaperones for NPC1(I1061T) mutant. 

PMID- 24928401
TI  - Design, synthesis and antioxidant activity evaluation of novel beta-elemene
      derivatives.
AB  - Forty beta-elemene derivatives were prepared and their antioxidant activity in
      H2O2-treated human umbilical vein endothelial cells (HUVECs) was first
      investigated. Among which, the dimer compounds 5r and 5s exhibited the most
      potent antioxidant activity against reactive oxygen species production.
      Meanwhile, 5r and 5s led to a significant increase in superoxide dismutase and
      nitric oxide levels and decrease in malonyldialdehyde and lactate dehydrogenase
      contents. Furthermore, MTT assay showed that 5r and 5s did not produce obvious
      cytotoxicity and had significantly cytoprotective effects against oxidative
      damage on HUVECs. 

PMID- 24928402
TI  - Phenylpropanoid acid esters from Korean propolis and their antioxidant
      activities.
AB  - Ten phenylpropanoic acid esters were isolated from an ethanolic extract of Korean
      propolis. Their structures were elucidated by spectroscopic methods including NMR
      and ESI-MS. Caffeic acid esters with catechol moiety exhibited significant ABTS
      and DPPH radical scavenging activity and protective effect against DNA damage by
      a Fenton reaction. 

PMID- 24928403
TI  - Evaluation of the neuroprotective activity of stansin 6, a resin glycoside from
      Ipomoea stans.
AB  - Stansin 6 a tetrasaccharide resin glycoside isolated from the root of Ipomoea
      stans was evaluated as anticonvulsant and neuroprotective in kainic acid-induced
      seizures of rats. Intraperitoneal injection of kainic acid (10 mg/kg) induced
      typical behavioral seizures such as wet dog shakes and limbic seizures, and
      histopathological changes in the hippocampus (degeneration and loss of pyramidal
      cells in CA1 to CA4 areas). Stansin 6 (10-80 mg/kg) had no effect on the behavior
      of rats and did not induce hippocampal damage. Pretreatment with stansin 6
      inhibited convulsions in rats from kainic acid-induced seizures, reduced the
      degeneration pattern in the CA3 region, decreased astrocytic reactivity, and
      reduced the expression of IL-1beta and TNF-alpha induced by kainic acid. These
      results suggest that stansin 6 possesses neuroprotective and anticonvulsant
      activities.

PMID- 24928406
TI  - A new clandestine route of ethanol administration? Volume of vodka absorbed in
      commercially available tampons. An in vitro study.

PMID- 24928404
TI  - Anti-cancer activity of carbamate derivatives of melampomagnolide B.
AB  - Melampomagnolide B (MMB) is a natural sesquiterpene structurally related to
      parthenolide (PTL). We have shown that MMB exhibits anti-leukemic properties
      similar to PTL. Unlike PTL, the presence of a primary hydroxyl group in the MMB
      molecule allows the opportunity for examining the biological activity of a
      variety of conjugated analogs of MMB. We have now synthesized a series of
      carbamate analogs of MMB and evaluated these derivatives for anti-cancer activity
      against a panel of sixty human cancer cell lines. Analogs 6a and 6e exhibited
      promising anti-leukemic activity against human leukemia cell line CCRF-CEM with
      GI50 values of 680 and 620 nM, respectively. Analog 6a also showed GI50 values of
      1.98 and 1.38 MUM respectively, against RPMI-8226 and SR leukemia cell lines and
      GI50 values of 460 and 570 nM against MDA-MB-435 melanoma and MDA-MB-468 breast
      cancer cell lines, respectively. Analog 6e had GI50 values of 650 and 900 nM
      against HOP-92 non-small cell lung and RXF 393 renal cancer cell lines.

PMID- 24928405
TI  - Antioxidant effects of the highly-substituted carbazole alkaloids and their
      related carbazoles.
AB  - Antioxidant activities of 3-oxygenated and 3,4-dioxygenated carbazole alkaloids
      and their related carbazoles were comprehensively evaluated. In all assay
      systems, the 3,8-dihydroxycarbazoles carbazomadurin A (2) and B (3), and their
      synthetic precursors 2a and 3a exhibited higher antioxidant activities than the 3
      monohydroxycarbazoles carazostatin (1), and the synthetic precursors 4a and 4b of
      carquinostatin A (4). In particular, 2a and 3a exhibited strong scavenging
      activities due to the reducing ability of formyl group at the C-5 position of
      carbazoles. The results suggest that these compounds could serve as useful clues
      for designing and developing novel antioxidants. 

PMID- 24928407
TI  - A comparison of the supraclavicular and infraclavicular views for imaging the
      subclavian vein with ultrasound.
AB  - INTRODUCTION: Ultrasound guidance for central line placement in the subclavian
      vein (SCV) is more efficient and safer than landmark-based technique. The
      supraclavicular (SC) approach is an alternative to the infraclavicular (IC)
      approach, but the research is sparse. The objective was to determine which
      approach provides the best view. METHODS: This was a prospective anatomical
      survey of voluntary normovolemic patients. Four experienced emergency physicians
      and 1 resident scanned the right and left SCVs from SC and IC approaches. They
      assigned a score for the views obtained on a 5-point Likert scale. RESULTS:
      Ninety-eight patients were enrolled. Mean Likert scores for the 4 views were:
      right SC, 4.06 (95% confidence interval [CI], 0.22); right IC, 3.07 (95% CI,
      0.25); left SC, 3.82 (95% CI, 0.23); left IC, 3.12 (95% CI, 0.25). When combining
      data from right and left, the mean score for the SC view was significantly higher
      than the mean score for the IC view: 3.94 (95% CI, 0.16) vs 3.10 (95% CI, 0.18).
      The following ratings were obtained: right SC view was good or excellent in
      71.5%; left SC view was good or excellent in 66.3%; right IC view was good or
      excellent in 37.8%; and left IC view was good or excellent in 38.8%. CONCLUSION:
      The SC approach allows for a better view of the SCV on ultrasound than the IC
      approach. Future research should determine if this translates to a greater
      success rate when placing central lines in the SCV.

PMID- 24928408
TI  - Implementation of a clinical pathway based on a computerized physician order
      entry system for ischemic stroke attenuates off-hour and weekend effects in the
      ED.
AB  - BACKGROUND: Admission on weekends and off-hours has been associated with poor
      outcomes and mortality from acute stroke. The purpose of this study was to
      investigate whether an organized clinical pathway (CP) for ischemic stroke can
      effectively reduce the time from arrival to evaluation and treatment in the
      emergency department (ED) and improve outcomes, regardless of the time from
      arrival in the ED. METHODS: We conducted a retrospective analysis of all
      consecutive patients included in the prospective registry database in the Brain
      Salvage through Emergency Stroke Therapy program, which uses the computerized
      physician order entry (CPOE) system. Patients were classified based on their time
      of arrival in the ED: group 1, normal working hours on weekdays; group 2, off
      hours on weekdays; group 3, normal working hours on weekends; and group 4, off
      hours on weekends. Clinical outcomes were categorized according to 30 days in
      hospital mortality, in-hospital mortality, and the modified Rankin score during a
      single length of stay (LOS). RESULTS: No time intervals differed significantly
      among the 4 patient groups who received intravenous administration of tissue
      plasminogen activator (IV-tPA). Use of IV-tPA (P = .5110) was not affected by
      arrival in the ED on off-days or weekends. The overall mortality rate was 3.9%,
      and the median LOS was 7 days (Interquartile range (IQR), 5-10). By Kaplan-Meier
      analysis, the cumulative probability of mortality and survival did not differ
      significantly among the 4 groups over 30 days (P = .1557). CONCLUSION: An
      organized CP, based on CPOE, for ischemic stroke can effectively attenuate
      disparities in the time interval between ED arrival to evaluation and treatment
      regardless of ED arrival time. This pathway may also help to eliminate off-hour
      and weekend effects on outcomes from ischemic stroke.

PMID- 24928409
TI  - Prognostic evaluation of the troponin I elevation after multiple spontaneous
      shocks of the implantable cardioverter/defibrillator.
AB  - BACKGROUND: Multiple shocks of the implantable cardioverter/defibrillator (ICD)
      can cause myocardial injury, contributing to the progression of underlying heart
      disease. The aim was to evaluate if the elevation of troponin I after multiple
      ICD shocks has impact on the prognostic of these patients. METHODS: We evaluated
      patients with multiple ICD shocks (>3 shocks) in the last 24 hours. Troponin I
      was measured around 12 hours after the last shock. After this episode, these
      patients were followed; and events of death or heart failure hospitalization were
      recorded. RESULTS: Twenty-six patients were included in the study. Elevation of
      troponin I occurred in 16 patients (62%), who had received a higher number of
      shocks (14 +/- 9 vs 7 +/- 4, P = .03) and greater cumulative total voltage (455
      +/- 345 J vs 141 +/- 62 J, P = .03) compared to the group without elevation of
      this biomarker. We observed a positive correlation between troponin I and number
      of shocks (r = 0.70; P = .0001). Patients with troponin I elevation after
      multiple ICD shocks had higher risk of death or heart failure hospitalization
      (hazard ratio, 7.0; 95% confidence interval, 1.2-16.0; P = .03) compared with the
      group without elevation of this biomarker. After adjustment for age, sex, and
      number of shocks, the elevation of this biomarker remained as predictor of these
      events (hazard ratio, 16.0; 95% confidence interval, 1.7-151.0; P = .02).
      CONCLUSION: A large proportion of patients with multiple ICD shocks have troponin
      I elevation, and these patients have a higher risk of death or hospitalization
      due to heart failure.

PMID- 24928410
TI  - Cardiopulmonary arrest due to early hyperkalemia after liver injury.
AB  - Hyperkalemia due to crush syndrome after trauma is a well known fatal clinical
      condition, but early hyperkalemia with hemorrhage after trauma is a rare
      phenomenon. We report on a 5-year-old boy who bruised from the lumbers, had
      cardiopulmonary arrest caused by hyperkalemia, and underwent perihepatic packing
      twice before being discharged without any neurologic deficits. Clinicians should
      be vigilant for signs of hyperkalemia accompanying hemorrhagic shock, even in the
      early phase of trauma.

PMID- 24928411
TI  - Association of blood glucose at admission with outcomes in patients treated with
      therapeutic hypothermia after cardiac arrest.
AB  - BACKGROUND: It is well known that hyperglycemia is associated with poor outcomes
      in critically ill patients. We investigated the association between blood glucose
      level at admission and the outcomes of patients treated with therapeutic
      hypothermia (TH) after cardiac arrest. METHODS: A total of 883 cardiac arrest
      patients who were treated with TH were analyzed from the Korean Hypothermia
      Network retrospective registry. We examined the association of blood glucose at
      admission with survival and neurologic outcomes at hospital discharge. Favorable
      neurologic outcomes were defined as Cerebral Performance Category scores of 1 and
      2. RESULTS: The mean age of the sample was 56.7 +/- 16.2 years, 69.5% of subjects
      were male, and the mean blood glucose at admission was 14.1 +/- 7.0 mmol/L. After
      adjustment for sex, age, history of diabetes mellitus, hypertension, renal
      disease and stroke, time from arrest to return of spontaneous circulation,
      initial rhythm, witness status, bystander cardiopulmonary resuscitation, cause of
      arrest, and cumulative dose of adrenaline, the associations between glucose and
      outcomes were as follows: for favorable neurologic outcomes, an odds ratio of
      0.955 (95% confidence interval, 0.918-0.994); and for survival, an odds ratio of
      0.974 (95% confidence interval, 0.952-0.996). CONCLUSION: These results show that
      blood glucose level at admission is associated with survival and favorable
      neurologic outcomes at hospital discharge in patients treated with TH after
      cardiac arrest. Blood glucose level at admission could be a surrogate marker of
      ischemic insult severity during cardiac arrest. However, randomized, controlled
      evidence is needed to address the significance of tight glucose control during TH
      after cardiac arrest.

PMID- 24928412
TI  - CORR Insights((r)): Which Variables Are Associated With Patient-reported Outcomes
      After Discectomy? Review of SPORT Disc Herniation Studies.

PMID- 24928413
TI  - Associations of work-related factors and work engagement with mental and physical
      health: a 1-year follow-up study among older workers.
AB  - PURPOSE: The goals of this study were to determine whether, among older
      employees, unfavourable physical and psychosocial work-related factors were
      associated with poorer mental and physical health and whether high work
      engagement buffered the associations between unfavourable work-related factors
      and poorer health. METHODS: A 1-year longitudinal study with employed persons
      aged 45-64 was conducted within the Study on Transitions in Employment, Ability
      and Motivation (n = 8,837). Using an online questionnaire, work-related factors
      (physical: physical load; psychosocial: psychological job demands, autonomy, and
      support) and work engagement were measured at baseline and health at baseline and
      1-year follow-up. General linear models were used to assess associations of work
      related factors and work engagement with health. Tests of interaction terms
      assessed whether work engagement buffered the work-related factor-health
      associations. RESULTS: Unfavourable psychosocial work-related factors at baseline
      were associated with poorer mental health at follow-up. Higher physical load,
      higher psychological job demands, and lower autonomy at baseline were associated
      with poorer physical health at follow-up. Higher work engagement at baseline was
      related to better physical and especially better mental health during the 1-year
      follow-up. Work engagement had a small effect on the associations between work
      related factors and health. CONCLUSIONS: Among older employees, especially the
      promotion of a high work engagement and, to a lesser extent, favourable work
      related factors can be beneficial for mental health in particular.

PMID- 24928414
TI  - MicroRNAs and their applications in kidney diseases.
AB  - MicroRNAs (miRNAs) are short, non-coding RNAs that employ classic Watson-Crick
      base-pairing to identify their target genes, ultimately resulting in
      destabilization of their target mRNAs and/or inhibition of their translation. The
      role of miRNAs in a wide range of human diseases, including those afflicting the
      kidney, has been intensely investigated. However, there is still a vast dearth of
      knowledge regarding their specific mode of action and therapeutic effects in
      various kidney diseases. This review discusses the latest efforts to further our
      understanding of the basic biology of miRNAs, their impact on various kidney
      diseases and their potential as novel biomarkers and therapeutic agents. We
      initially provide an overview of miRNA biology and the canonical pathway
      implicated in their biogenesis. We then discuss commonly employed experimental
      strategies for miRNA research and highlight some of the newly described state-of
      the-art technologies to identify miRNAs and their target genes. Finally, we
      carefully examine the emerging role of miRNAs in the pathogenesis of various
      kidney diseases. 

PMID- 24928415
TI  - The biological effects of higher and lower positive end-expiratory pressure in
      pulmonary and extrapulmonary acute lung injury with intra-abdominal hypertension.
AB  - INTRODUCTION: Mechanical ventilation with high positive end-expiratory pressure
      (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS)
      and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung
      injury remains controversial. We hypothesized that in the presence of acute lung
      injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and
      minimize lung injury; and 2) the biological effects of higher PEEP are more
      effective in extrapulmonary (exp) than pulmonary (p) ALI. METHODS: In 48 adult
      male Wistar rats, ALIp and ALIexp were induced by Escherichia coli
      lipopolysaccharide intratracheally and intraperitoneally, respectively. After 24
      hours, animals were anesthetized and mechanically ventilated (tidal volume of 6
      mL/kg). IAH (15 mmHg) was induced and rats randomly assigned to PEEP of 5
      (PEEP5), 7 (PEEP7) or 10 (PEEP10) cmH2O for 1 hour. RESULTS: In both ALIp and
      ALIexp, higher PEEP levels improved oxygenation. PEEP10 increased alveolar
      hyperinflation and epithelial cell damage compared to PEEP5, independent of ALI
      etiology. In ALIp, PEEP7 and PEEP10 increased lung elastance compared to PEEP5
      (4.3 +/- 0.7 and 4.3 +/- 0.9 versus 3.1 +/- 0.3 cmH2O/mL, respectively, P <0.01),
      without changes in alveolar collapse, interleukin-6, caspase-3, type III
      procollagen, receptor for advanced glycation end-products, and vascular cell
      adhesion molecule-1 expressions. Moreover, PEEP10 increased diaphragmatic injury
      compared to PEEP5. In ALIexp, PEEP7 decreased lung elastance and alveolar
      collapse compared to PEEP5 (2.3 +/- 0.5 versus 3.6 +/- 0.7 cmH2O/mL, P <0.02, and
      27.2 (24.7 to 36.8) versus 44.2 (39.7 to 56.9)%, P <0.05, respectively), while
      PEEP7 and PEEP10 increased interleukin-6 and type III procollagen expressions, as
      well as type II epithelial cell damage compared to PEEP5. CONCLUSIONS: In the
      current models of ALI with IAH, in contrast to our primary hypothesis, higher
      PEEP is more effective in ALIp than ALIexp as demonstrated by the activation of
      biological markers. Therefore, higher PEEP should be used cautiously in the
      presence of IAH and ALI, mainly in ALIexp.

PMID- 24928416
TI  - Differential efficiency in exogenous DNA acquisition among closely related
      Salmonella strains: implications in bacterial speciation.
AB  - BACKGROUND: Acquisition of exogenous genetic material is a key event in bacterial
      speciation. It seems reasonable to assume that recombination of the incoming DNA
      into genome would be more efficient with higher levels of relatedness between the
      DNA donor and recipient. If so, bacterial speciation would be a smooth process,
      leading to a continuous spectrum of genomic divergence of bacteria, which,
      however, is not the case as shown by recent findings. The goal of this study was
      todetermine if DNA transfer efficiency is correlated with the levels of sequence
      identity. RESULTS: To compare the relative efficiency of exogenous DNA
      acquisition among closely related bacteria, we carried out phage-mediated
      transduction and plasmid-mediated transformation in representative Salmonella
      strains with different levels of relatedness. We found that the efficiency was
      remarkably variable even among genetically almost identical bacteria. Although
      there was a general tendency that more closely related DNA donor-recipient pairs
      had higher transduction efficiency, transformation efficiency exhibited over a
      thousand times difference among the closely related Salmonella strains.
      CONCLUSION: DNA acquisition efficiency is greatly variable among bacteria that
      have as high as over 99% identical genetic background, suggesting that bacterial
      speciation involves highly complex processes affected not only by whether
      beneficial exogenous DNA may exist in the environment but also the "readiness" of
      the bacteria to accept it.

PMID- 24928417
TI  - Learning in an exotic social wasp while relocating a food source.
AB  - In this paper we review several studies on Vespulagermanica behavioral plasticity
      while relocating a food source in natural environments. This exotic social wasp,
      which has become established in many parts of the world, displays diverse
      cognitive abilities when foraging. Given its successful invasiveness worldwide,
      our initial hypothesis was that this species has great behavioral plasticity,
      which enables it to face environmental uncertainty. In our work we have analyzed
      foraging behavior associated with undepleted resources. Throughout several
      experiments, rapid learning was observed in this species; after few learning
      experiences they associate diverse contextual cues with a food source. However,
      by exploring wasp behavior when food suddenly disappeared, either because it had
      been removed or displaced, we found that they continued searching over a no
      longer rewarding site for a considerable period of time, suggesting that past
      experience can hinder new learning. Particularly surprising is the fact that when
      food was displaced nearby, wasps persisted in searching over the empty dish,
      ignoring the presence of food close by. We propose that this species could be a
      suitable model for studying cognitive plasticity in relation to environmental
      uncertainty. 

PMID- 24928419
TI  - Acute kidney injury in adults receiving extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill
      patients such as patients with postcardiotomy cardiogenic shock or life
      threatening respiratory failure. Acute kidney injury (AKI) that develops during
      ECMO is associated with a very poor outcome, possibly because of accumulated
      extravascular water causing interstitial overload, impaired oxygen transport
      through tissues, and increased extravascular lung water volume with impaired O(2)
      transport. Increased water is associated with subsequent organ dysfunction,
      particularly of the heart, lungs, and brain. Based on single-center studies, the
      incidence of AKI is 70-85% in ECMO patients. Therefore, renal replacement therapy
      is required in approximately 50% of these patients. This review summarizes three
      modalities that can be used to introduce renal replacement therapy to patients on
      ECMO, the pathophysiology of AKI in ECMO, and the impact of AKI on mortality.
      This review also identifies specific research-focused questions that need to be
      addressed to predict AKI early and to improve outcomes in this at-risk adult
      population.

PMID- 24928418
TI  - Effectiveness and safety of extracranial carotid stent placement: a nationwide
      self-controlled case-series study.
AB  - BACKGROUND: Carotid angioplasty and stent (CAS) placement has emerged as an
      attractive revascularization strategy for patients with internal carotid artery
      stenosis. However, the effectiveness and safety of CAS were not fully evaluated,
      mainly because of methodological difficulties in finding an appropriate
      comparison group. METHODS: Patients who underwent CAS were identified from
      Taiwan's National Health Insurance claims database between 2005 and 2008. The
      incidence rate of ischemic stroke after CAS was compared with that of the year
      prior to the procedure using a self-controlled case series analysis and a
      conditional Poisson regression model. Logistic regression was conducted to
      identify factors associated with poor outcome. RESULTS: A total of 1258 patients
      who had undergone CAS were included, and 73 cases (5.8%) of death or ischemic
      stroke occurred during the index hospitalization. Within 1 year after CAS, 74
      patients died and 80 experienced an ischemic stroke. Of the 1184 patients who
      were followed for 360 days, the rate ratio for ischemic stroke decreased to 0.21
      (95% CI: 0.08-0.51) between 31 and 180 days, and 0.10 (95% CI: 0.03-0.32) between
      181 and 360 days. Statin therapy was associated with a reduced risk of death or
      ischemic stroke in the 1(st) month (odds ratio of 0.53; 95% CI: 0.32-0.90).
      Conversely, the use of nonsteroidal anti-inflammatory agents, possibly histamine
      2 receptor blockers, and CAS performed by low-volume operators were associated
      with a twofold increased risk. CONCLUSION: CAS reduced the long-term risk for
      ischemic stroke. Self-controlled case series analysis might be an appropriate
      design for evaluating device safety and effectiveness.

PMID- 24928420
TI  - Why peer assessment helps to improve clinical performance in undergraduate
      physical therapy education: a mixed methods design.
AB  - BACKGROUND: Peer Assessment (PA) in health professions education encourages
      students to develop a critical attitude towards their own and their peers'
      performance. We designed a PA task to assess students' clinical skills (including
      reasoning, communication, physical examination and treatment skills) in a role
      play that simulated physical therapy (PT) practice. Students alternately
      performed in the role of PT, assessor, and patient. Oral face-to-face feedback
      was provided as well as written feedback and scores.This study aims to explore
      the impact of PA on the improvement of clinical performance of undergraduate PT
      students. METHODS: The PA task was analyzed and decomposed into task elements. A
      qualitative approach was used to explore students' perceptions of the task and
      the task elements. Semi-structured interviews with second year students were
      conducted to explore the perceived impact of these task elements on performance
      improvement. Students were asked to select the elements perceived valuable, to
      rank them from highest to lowest learning value, and to motivate their choices.
      Interviews were transcribed verbatim and analyzed, using a phenomenographical
      approach and following template analysis guidelines. A quantitative approach was
      used to describe the ranking results. RESULTS: Quantitative analyses showed that
      the perceived impact on learning varied widely. Performing the clinical task in
      the PT role, was assigned to the first place (1), followed by receiving expert
      feedback (2), and observing peer performance (3). Receiving peer feedback was not
      perceived the most powerful task element.Qualitative analyses resulted in three
      emerging themes: pre-performance, true-performance, and post-performance triggers
      for improvement. Each theme contained three categories: learning activities,
      outcomes, and conditions for learning.Intended learning activities were reported,
      such as transferring prior learning to a new application context and unintended
      learning activities, such as modelling a peer's performance. Outcomes related to
      increased self-confidence, insight in performance standards and awareness of
      improvement areas. Conditions for learning referred to the quality of peer
      feedback. CONCLUSIONS: PA may be a powerful tool to improve clinical performance,
      although peer feedback is not perceived the most powerful element. Peer assessors
      in undergraduate PT education use idiosyncratic strategies to assess their peers'
      performance.

PMID- 24928421
TI  - Comparison of the immunoperoxidase monolayer assay and three commercial ELISAs
      for detection of antibodies against porcine circovirus type 2.
AB  - The aim of this study was to compare and correlate antibody titres against
      porcine circovirus type 2 (PCV2) in porcine sera (n = 1270) obtained by
      immunoperoxidase monolayer assay (IPMA) with the results of three commercial
      ELISAs (designated E1, E2 and E3). The correlation between IPMA and ELISA results
      was excellent (r(2) >= 0.90). Compared to IPMA, E2 had the highest sensitivity
      (93.0%), followed by E3 (90.1%) and E1 (85.0%); the specificity was 100% for all
      tests. All three commercial ELISAs had predictive values similar to those of IPMA
      and could be used to monitor antibody responses against PCV2 infection and/or
      vaccination.

PMID- 24928422
TI  - Viral causes of feline lymphoma: retroviruses and beyond.
AB  - The most widely recognised cause of feline lymphoma is the gammaretrovirus feline
      leukaemia virus (FeLV). Research into the mechanisms of cellular transformation
      employed by FeLV and other oncogenic retroviruses has provided as much
      information on the regulation of eukaryotic cell growth and differentiation as it
      has about cancer. The recognition that a cancer has a viral cause opens up the
      possibility of novel treatments that spare the host from cytotoxic side-effects
      by specifically targeting the virus, or the host's immune response to it. The
      ultimate prize for viral-associated cancers is their prevention. Vaccination and
      changes in management practices have seen the global prevalence of FeLV infection
      fall and, with it, the incidence of FeLV-related cancers. Remarkably, in the face
      of this success, the prevalence of feline lymphoma remains high. At least one
      other virus, the lentivirus feline immunodeficiency virus (FIV), accounts for
      some of these cases. Transformation by FIV involves incompletely understood
      mechanisms that are distinct from those employed by FeLV. This review will focus
      on the current understanding of FeLV-associated and FIV-associated lymphoma and
      consider whether yet more viral aetiologies could be waiting to be discovered.

PMID- 24928423
TI  - Headache in sleep apnea syndrome: epidemiology and pathophysiology.
AB  - This review investigates the relation between obstructive sleep apnea and sleep
      apnea headache, migraine and tension-type headache. Focus is made on studies from
      the general population with interviews conducted by a physician and obstructive
      sleep apnea confirmed by polysomnography. Obstructive sleep apnea syndrome is
      observed in 3% of the middle-aged population. The prevalence of sleep apnea
      headache in this population is 12%-18%, while morning headache with similar
      symptomatology as sleep apnea headache occur in 5%-8% of the general population.
      People with sleep apnea headache did have significantly more minutes below 90%
      oxygen saturation (23.1 min vs. 1.9 min, p = 0.002), higher level of average
      oxygen desaturation (5.9% vs. 4.5%, p < 0.001) and lower average of the lowest
      oxygen saturation (80.9% vs. 88.5%, p < 0.001) than people with morning headache.
      A comparison of those with obstructive sleep apnea with or without sleep apnea
      headache showed no significant differences. Thus, oxygen desaturation alone
      cannot explain the pathophysiology of sleep apnea headache. Obstructive sleep
      apnea and migraine, and obstructive sleep apnea and tension-type headache are not
      related in the general population. The cause of sleep apnea headache remains to
      be elucidated.

PMID- 24928424
TI  - Can classic moral stories promote honesty in children?
AB  - The classic moral stories have been used extensively to teach children about the
      consequences of lying and the virtue of honesty. Despite their widespread use,
      there is no evidence whether these stories actually promote honesty in children.
      This study compared the effectiveness of four classic moral stories in promoting
      honesty in 3- to 7-year-olds. Surprisingly, the stories of "Pinocchio" and "The
      Boy Who Cried Wolf" failed to reduce lying in children. In contrast, the
      apocryphal story of "George Washington and the Cherry Tree" significantly
      increased truth telling. Further results suggest that the reason for the
      difference in honesty-promoting effectiveness between the "George Washington"
      story and the other stories was that the former emphasizes the positive
      consequences of honesty, whereas the latter focus on the negative consequences of
      dishonesty. When the "George Washington" story was altered to focus on the
      negative consequences of dishonesty, it too failed to promote honesty in
      children. 

PMID- 24928425
TI  - Differences in the tissue tropism to chicken oviduct epithelial cells between
      avian coronavirus IBV strains QX and B1648 are not related to the sialic acid
      binding properties of their spike proteins.
AB  - The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major
      poultry pathogen. A characteristic feature of IBV is the occurrence of many
      different strains belonging to different serotypes, which makes a complete
      control of the disease by vaccinations a challenging task. Reasons for
      differences in the tissue tropism and pathogenicity between IBV strains, e.g. a
      predilection for the kidneys or the oviduct are still an open question. Strains
      of the QX genotype have been major pathogens in poultry flocks in Asia, Europe
      and other parts of the world. They are the cause of severe problems with kidney
      disease and reproductive tract disorders. We analysed infectivity and binding
      properties of the QX strain and compared them with those of the nephropathogenic
      strain B1648. As most IBV strains do not infect permanent cell lines and show
      infection only in primary chicken cells of the target organs, we developed a
      culture system for chicken oviduct explants. The epithelial cells of the oviduct
      showed a high susceptibility to infection by the QX strain and were almost
      resistant to infection by the nephropathogenic B1648 strain. Binding tests with
      isolated primary oviduct epithelial cells and soluble S1 proteins revealed that
      S1 proteins of two IBV strains bound with the same efficiency to oviduct
      epithelial cells. This attachment was sialic acid dependent, indicating that the
      sugar binding property of IBV spike proteins is not the limiting factor for
      differences in infection efficiency for the oviduct of the corresponding viruses.

PMID- 24928426
TI  - Basidioascus persicus sp. nov., a yeast-like species of the order
      Geminibasidiales isolated from soil.
AB  - A novel species of basidiomycetes was isolated from kitchen garden soil in
      Shahryar city, Tehran province, Iran. Molecular and conventional methods were
      employed to identify and classify this single isolate. Morphologically, the
      isolate was considered yeast-like with hyaline and oval cells reproducing by
      monopolar budding, forming ballistoconidia, hyphae, arthroconidia and
      didymospores. Basidia and basidiospores resembling those produced by Basidioascus
      species were observed. Sequencing and Bayesian phylogenetic analysis of rRNA
      genes and the internal transcribed spacer region revealed its sister relationship
      to described species of the genus Basidioascus. Assimilation and fermentation
      tests, cell-wall carbohydrate analysis and enzyme activity tests were performed
      to provide insight into the metabolism of the isolate. Based on morphology,
      physiology and phylogeny of rRNA gene sequences, the isolate was shown to
      represent a novel species of the genus Basidioascus, described as Basidioascus
      persicus sp. nov. (holotype IBRC P1010180(T) = ex-type IBRC M30078(T) = isotype
      CBS 12808(T)). The MycoBank number of the novel species is MB 804703. An emended
      description of the genus Basidioascus is also provided. 

PMID- 24928427
TI  - Morphology and phylogenetic analysis of two oxytrichid soil ciliates from China,
      Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam,
      1983 (Protista, Ciliophora, Hypotrichia).
AB  - The morphology and infraciliature of two hypotrichous ciliates, Oxytricha
      paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983,
      collected respectively from the surface of a sandy soil in the Huguang mangrove
      forest, Zhanjiang, China, and the surface of soil in a forest beside Ziwu Road,
      Xian, north-west China, were examined. O. paragranulifera n. sp. is characterized
      by an elongate body with slightly tapered anterior end, two macronuclear nodules
      and two micronuclei, paroral and endoral in Stylonychia-pattern, colourless
      cortical granules distributed in clusters or irregular short rows, adoral zone
      occupying 37 % of the body length, marginal rows almost confluent posteriorly,
      six dorsal kineties and three caudal cirri, caudal cirri and dorsal bristles
      almost indistinguishable when viewed in vivo. The well-known O. granulifera
      Foissner and Adam, 1983 was also redescribed and can be separated from the novel
      species by having cortical granules arranged along dorsal kineties and marginal
      rows on both sides (vs grouped in clusters as well as in short irregular rows),
      paroral and endoral in Oxytricha-pattern (vs in Stylonychia-pattern),
      macronuclear nodules obviously detached (vs adjacent) and a non-saline
      terrestrial habitat (vs saline terrestrial). The separation of these two taxa is
      also firmly supported by the molecular data, which show a significant difference
      between the two in their SSU rRNA gene sequences (similarity 97.1 %).
      Phylogenetic analyses based on SSU rRNA gene sequence data suggest a close
      relationship within the Oxytrichidae assemblage between O. paragranulifera n. sp.
      and O. granulifera. 

PMID- 24928428
TI  - Paenibacillus lupini sp. nov., isolated from nodules of Lupinus albus.
AB  - A bacterial strain designated RLAHU15(T) was isolated from root nodules of
      Lupinus albus in Spain. Phylogenetic analyses based on 16S rRNA gene sequences
      placed the isolate in the genus Paenibacillus, with its closest relatives being
      Paenibacillus catalpae D75(T), Paenibacillus glycanilyticus DS-1(T),
      Paenibacillus endophyticus PECAE04(T) and Paenibacillus xinjiangensis B538(T)
      with 98.8 %, 98.9 %, 97.4 % and 97.4 % similarity, respectively. DNA-DNA
      hybridization studies showed values lower than 45 % between the strain RLAHU15(T)
      and any of these species. The isolate was a Gram-stain positive, motile and
      sporulating rod. Catalase activity was weak and oxidase activity was positive.
      Casein and starch were hydrolysed but gelatin was not. Growth was supported by
      many carbohydrates and organic acids as carbon sources. MK-7 was the only
      menaquinone detected and anteiso-C15 : 0 and iso-C16 : 0 were the major fatty
      acids. The major polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, three unidentified phospholipids
      and an unidentified lipid. meso-Diaminopimelic acid was detected in the
      peptidoglycan. The DNA G+C content was 54.4 mol%. Phylogenetic, chemotaxonomic
      and phenotypic analyses showed that strain RLAHU15(T) represents a novel species
      of the genus Paenibacillus, for which the name Paenibacillus lupini sp. nov. is
      proposed. The type strain is RLAHU15(T) ( = LMG 27296(T) = CECT 8235(T)). 

PMID- 24928429
TI  - Shape and position of the node and notochord along the bilateral plane of
      symmetry are regulated by cell-extracellular matrix interactions.
AB  - The node and notochord (and their equivalents in other species) are essential
      signaling centers, positioned along the plane of bilateral symmetry in developing
      vertebrate embryos. However, genes and mechanisms regulating morphogenesis of
      these structures and their placement along the embryonic midline are not well
      understood. In this work, we provide the first evidence that the position of the
      node and the notochord along the bilateral plane of symmetry are under genetic
      control and are regulated by integrin alpha5beta1 and fibronectin in mice. We
      found that the shape of the node is often inverted in integrin alpha5-null and
      fibronectin-null mutants, and that the positioning of node and the notochord is
      often skewed away from the perceived plane of embryonic bilateral of symmetry.
      Our studies also show that the shape and position of the notochord are dependent
      on the shape and embryonic placement of the node. Our studies suggest that
      fibronectin regulates the shape of the node by affecting apico-basal polarity of
      the nodal cells. Taken together, our data indicate that cell-extracellular matrix
      interactions mediated by integrin alpha5beta1 and fibronectin regulate the
      geometry of the node as well as the placement of the node and notochord along the
      plane of bilateral symmetry in the mammalian embryo. 

PMID- 24928430
TI  - Fission yeast mtr1p regulates interphase microtubule cortical dwell-time.
AB  - The microtubule cytoskeleton plays important roles in cell polarity, motility and
      division. Microtubules inherently undergo dynamic instability, stochastically
      switching between phases of growth and shrinkage. In cells, some microtubule
      associated proteins (MAPs) and molecular motors can further modulate microtubule
      dynamics. We present here the fission yeast mtr1(+), a new regulator of
      microtubule dynamics that appears to be not a MAP or a motor. mtr1-deletion
      (mtr1Delta) primarily results in longer microtubule dwell-time at the cell tip
      cortex, suggesting that mtr1p acts directly or indirectly as a destabilizer of
      microtubules. mtr1p is antagonistic to mal3p, the ortholog of mammalian EB1,
      which stabilizes microtubules. mal3Delta results in short microtubules, but can
      be partially rescued by mtr1Delta, as the double mutant mal3Delta mtr1Delta
      exhibits longer microtubules than mal3Delta single mutant. By sequence homology,
      mtr1p is predicted to be a component of the ribosomal quality control complex.
      Intriguingly, deletion of a predicted ribosomal gene, rps1801, also resulted in
      longer microtubule dwell-time similar to mtr1Delta. The double-mutant mal3Delta
      rps1801Delta also exhibits longer microtubules than mal3Delta single mutant
      alone. Our study suggests a possible involvement of mtr1p and the ribosome
      complex in modulating microtubule dynamics. 

PMID- 24928432
TI  - The STAFF studies of the first 5 minutes of percutaneous coronary angioplasty
      balloon occlusion in man.
AB  - The Staff Studies comprise a database of 228 patients undergoing elective 5
      minute coronary artery balloon occlusion angioplasty at a single center in the
      pre-stent era in whom standard and high-frequency electrocardiographic and
      nuclear information was obtained immediately before, during and after balloon
      occlusion. The data were then analyzed by multiple investigators at different
      international academic centers from different perspectives. Simulating in a
      clinical setting the first 5 minutes of a heart attack, this database, now in
      digital format, is the largest database to date documenting standard and high
      frequency ECG changes from the onset and for 5 minutes during acute coronary
      artery occlusion, with resting and occlusion imaging in a subset of these
      patients. The history, methodology, and legacy of these studies are discussed in
      this paper.

PMID- 24928431
TI  - Role of the miR-17~92 cluster family in cerebellar and medulloblastoma
      development.
AB  - The miR-17~92 cluster family is composed of three members encoding microRNAs that
      share seed sequences. To assess their role in cerebellar and medulloblastoma (MB)
      development, we deleted the miR-17~92 cluster family in Nestin-positive neural
      progenitors and in mice heterozygous for the Sonic Hedgehog (SHH) receptor
      Patched 1 (Ptch1(+/-)). We show that mice in which we conditionally deleted the
      miR-17~92 cluster (miR-17~92(floxed/floxed); Nestin-Cre(+)) alone or together
      with the complete loss of the miR-106b~25 cluster (miR-106b~25(-/-)) were born
      alive but with small brains and reduced cerebellar foliation. Remarkably,
      deletion of the miR-17~92 cluster abolished the development of SHH-MB in Ptch1(+/
      ) mice. Using an orthotopic transplant approach, we showed that granule neuron
      precursors (GNPs) purified from the cerebella of postnatal day 7 (P7) Ptch1(+/-);
      miR-106b~25(-/-) mice and overexpressing Mycn induced MBs in the cortices of
      naive recipient mice. In contrast, GNPs purified from the cerebella of P7
      Ptch1(+/-); miR-17~92(floxed/floxed); Nestin-Cre(+) animals and overexpressing
      Mycn failed to induce tumors in recipient animals. Taken together, our findings
      demonstrate that the miR-17~92 cluster is dispensable for cerebellar development,
      but required for SHH-MB development. 

PMID- 24928433
TI  - Fasting plasma glucose and incident heart failure risk: a population-based cohort
      study and new meta-analysis.
AB  - BACKGROUND: There remains uncertainty regarding the association between fasting
      plasma glucose (FPG) and risk of heart failure (HF) in individuals without a
      history of diabetes. METHODS AND RESULTS: We assessed the association between FPG
      and HF risk in a population-based cohort of 1,740 men aged 42-61 years who were
      free from HF or diabetes at baseline. During a mean follow-up of 20.4 years, 146
      participants developed HF. In age-adjusted analysis, the hazard ratio (HR) for HF
      per 1 mmol/L increase in FPG was 1.34 (95% confidence interval 1.22-1.48). This
      association persisted after adjusting for established HF risk factors: HR 1.27,
      95% confidence interval 1.14-1.42. The findings remained consistent across
      several clinical subgroups and in analyses excluding incident coronary heart
      disease or diabetes during follow-up. In a meta-analysis of 10 prospective
      studies involving 4,213 incident HF cases, the HR for HF per 1 mmol/L increase in
      FPG level was 1.11 (95% confidence interval 1.04-1.17), with evidence of
      heterogeneity between studies (I(2) = 79%; 95% confidence interval 63%-89%; P <
      .001). The corresponding HR was 1.12 (95% confidence interval 1.08-1.18) on
      exclusion of the single study that accounted for the heterogeneity. CONCLUSIONS:
      There exists a positive, continuous, and independent association between FPG and
      risk for HF. Studies are warranted to evaluate the causal relevance of these
      findings.

PMID- 24928434
TI  - A method to enhance the magnitude of tactile hypersensitivity following spinal
      nerve ligation in rats.
AB  - BACKGROUND: The rat L5/L6 spinal nerve ligation model (SNL) has been widely used
      to investigate putative analgesics. Pursuit of novel therapies in preclinical
      settings requires models with consistent and reproducible phenotypes. NEW METHOD:
      We assessed the effects of repetitive stimulation of the hindpaws of SNL and Sham
      surgery rats during the 2 weeks immediately after surgery on the overall rate of
      achieving tactile hypersensitivity, as well as the magnitude of the
      hypersensitivity compared to unprimed rats. Beginning on day 2 post-surgery, and
      continuing on alternate days for a total of seven sessions, animals underwent
      light brushing/tapping (termed priming) of the hindpaws ipsilateral and
      contralateral to surgery. RESULTS: Priming the ipsilateral hindpaw enhanced the
      magnitude of tactile hypersensitivity such that the baseline withdrawal threshold
      (BWT) for primed SNL animals was significantly lower than unprimed SNL animals
      over post-surgical days 15-29. BWT was not different between primed and unprimed
      Sham rats. The percentage of SNL primed animals meeting the a priori criterion
      for tactile hypersensitivity of paw withdrawal threshold less than 2.0 grams was
      98.9%+/-1.1%. COMPARISON WITH EXISTING METHOD: SNL rats that did not receive
      stimulation (unprimed) showed significantly higher baseline hypersensitivity when
      evaluated on days 15-29, exemplified by only 34.5%+/-7.2% meeting the established
      <2.0g criterion. CONCLUSION: Our data indicate that tactile priming during the 2
      weeks immediately after SNL surgery enhances the magnitude of tactile
      hypersensitivity in the SNL model, and provide an optimized assay for evaluating
      putative analgesics.

PMID- 24928435
TI  - Do we know how much we put on the plate? Assessment of the accuracy of self
      estimated versus weighed vegetables and whole grain portions using an Intelligent
      Buffet at the FoodScape Lab.
AB  - The aim of this study was to assess the accuracy of self-estimated vegetable and
      whole grain serving sizes in a self-served buffet meal. The study took place in a
      laboratory setting where an Intelligent Buffet was used to register the exact
      weight of each food type that was self-served by each participant. The initial
      sample consisted of 58 participants recruited from Aalborg University in
      Copenhagen, of which 52 participants (59% male) provided complete estimates on
      the weight of whole grains and 49 participants (63% male) provided complete
      estimates on the weight of vegetable servings in their meal. The majority of the
      participants were students aged 20-29 years (85% for whole grain responses and
      82% for vegetable responses). Significant differences between self-estimated and
      actual portion size estimates were observed for both vegetables and whole grains
      (P < 0.001). The mean self-estimated weight of a vegetable serving was 218(+/
      134) g compared to the mean actual weight of 74(+/-44) g. The mean self-estimated
      and mean actual weights of a whole grain serving were 36(+/-34) g and 10(+/-9) g,
      respectively. There was no significant correlation between self-estimated and
      actual weights for each food group (P > 0.05). In conclusion, the participants'
      ability to accurately assess the serving size of vegetables and whole grains in a
      self-served meal did not correspond with the actual amount served. This may have
      implications for consumer interpretation of dietary recommendations used in
      nutrition interventions in Denmark. 

PMID- 24928436
TI  - Enhancing single-molecule fluorescence with nanophotonics.
AB  - Single-molecule fluorescence spectroscopy has become an important research tool
      in the life sciences but a number of limitations hinder the widespread use as a
      standard technique. The limited dynamic concentration range is one of the major
      hurdles. Recent developments in the nanophotonic field promise to alleviate these
      restrictions to an extent that even low affinity biomolecular interactions can be
      studied. After motivating the need for nanophotonics we introduce the basic
      concepts of nanophotonic devices such as zero mode waveguides and nanoantennas.
      We highlight current applications and the future potential of nanophotonic
      approaches when combined with biological systems and single-molecule
      spectroscopy. 

PMID- 24928437
TI  - In vitro activation of NAD-dependent alcohol dehydrogenases by Nudix hydrolases
      is more widespread than assumed.
AB  - In the Gram-positive methylotroph Bacillus methanolicus, methanol oxidation is
      catalyzed by an NAD-dependent methanol dehydrogenase (Mdh) that belongs to the
      type III alcohol dehydrogenase (Adh) family. It was previously shown that the in
      vitro activity of B. methanolicus Mdh is increased by the endogenous activator
      protein Act, a Nudix hydrolase. Here we show that this feature is not unique, but
      more widespread among type III Adhs in combination with Act or other Act-like
      Nudix hydrolases. In addition, we studied the effect of site directed mutations
      in the predicted active site of Mdh and two other type III Adhs with regard to
      activity and activation by Act. 

PMID- 24928438
TI  - Nanopores formed by DNA origami: a review.
AB  - Nanopores have emerged over the past two decades to become an important technique
      in single molecule experimental physics and biomolecule sensing. Recently DNA
      nanotechnology, in particular DNA origami, has been used for the formation of
      nanopores in insulating materials. DNA origami is a very attractive technique for
      the formation of nanopores since it enables the construction of 3D shapes with
      precise control over geometry and surface functionality. DNA origami has been
      applied to nanopore research by forming hybrid architectures with solid state
      nanopores and by direct insertion into lipid bilayers. This review discusses
      recent experimental work in this area and provides an outlook for future avenues
      and challenges. 

PMID- 24928439
TI  - MicroRNAs function as cis- and trans-acting modulators of peripheral circadian
      clocks.
AB  - Based on their extracellular expression and targeting of the clock gene Bmal1,
      miR-142-3p and miR-494 were analyzed for evidence of vesicle-mediated
      communication between cells and intracellular functional activity. Our studies
      demonstrate that: miR-142-3p+miR-494 overexpression decreases endogenous BMAL1
      levels, increases the period of Per2 oscillations, and increases extracellular
      miR-142-3p/miR-494 abundance in conditioned medium; miRNA-enriched medium
      increases intracellular expression of miR-142-3p and represses Bmal1 3'-UTR
      activity in naive cells; and inhibitors of vesicular trafficking modulate
      intercellular communication of these miRNAs and ensemble Per2 rhythms. Thus, miR
      142-3p and miR-494 may function as cis- and trans-acting signals contributing to
      local temporal coordination of cell-autonomous circadian clocks. 

PMID- 24928440
TI  - Challenges in quantitative single molecule localization microscopy.
AB  - Single molecule localization microscopy (SMLM), which can provide up to an order
      of magnitude improvement in spatial resolution over conventional fluorescence
      microscopy, has the potential to be a highly useful tool for quantitative
      biological experiments. It has already been used for this purpose in varied
      fields in biology, ranging from molecular biology to neuroscience. In this review
      article, we briefly review the applications of SMLM in quantitative biology, and
      also the challenges involved and some of the solutions that have been proposed.
      Due to its advantages in labeling specificity and the relatively low overcounting
      caused by photoblinking when photo-activable fluorescent proteins (PA-FPs) are
      used as labels, we focus specifically on Photo-Activated Localization Microscopy
      (PALM), even though the ideas presented might be applicable to SMLM in general.
      Also, we focus on the following three quantitative measurements: single molecule
      counting, analysis of protein spatial distribution heterogeneity and co
      localization analysis. 

PMID- 24928441
TI  - The polycomb group protein EZH2 inhibits lung cancer cell growth by repressing
      the transcription factor Nrf2.
AB  - EZH2 is a key component of the polycomb PRC2 complex and functions as a histone
      H3 Lys27 (H3K27) trimethyltransferase. Here we show that EZH2 is down-regulated
      in human non-small cell lung cancer and low EZH2 expression predicts poor
      survival. Further we demonstrate that EZH2 inhibits lung cancer cell
      proliferation and colony formation in vitro and growth in vivo. We found that
      EZH2 binds to the promoter of Nrf2, where it increases H3K27me3 and represses
      Nrf2 expression. Finally, Nrf2 seems to be essential for the hyper proliferation
      of lung cancer cells in the absence of EZH2. 

PMID- 24928442
TI  - miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human
      mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) have self-renewal and differentiation
      capabilities but the regulatory mechanisms of MSC fate determination remain
      poorly understood. Here, we aimed to identify microRNAs enriched in hMSCs that
      modulate differentiation commitments. Microarray analysis revealed that miR-140
      5p is commonly enriched in undifferentiated hMSCs from various tissue sources.
      Moreover, bioinformatic analysis and luciferase reporter assay validated that miR
      140-5p directly represses bone morphogenic protein 2 (BMP2). Furthermore,
      blocking miR-140-5p in hMSCs increased the expression of BMP signaling components
      and critical regulators of osteogenic differentiation. We propose that miR-140-5p
      functionally inhibits osteogenic lineage commitment in undifferentiated hMSCs. 

PMID- 24928443
TI  - Assay for characterizing the recovery of vertebrate cells for adhesion
      measurements by single-cell force spectroscopy.
AB  - Single-cell force spectroscopy (SCFS) is becoming a widely used method to
      quantify the adhesion of a living cell to a substrate, another cell or tissue.
      The high sensitivity of SCFS permits determining the contributions of individual
      cell adhesion molecules (CAMs) to the adhesion force of an entire cell. However,
      to prepare adherent cells for SCFS, they must first be detached from tissue
      culture flasks or plates. EDTA and trypsin are often applied for this purpose.
      Because cellular properties can be affected by this treatment, cells need to
      recover before being further characterized by SCFS. Here we introduce atomic
      force microscopy (AFM)-based SCFS to measure the mechanical and adhesive
      properties of HeLa cells and mouse embryonic kidney fibroblasts while they are
      recovering after detachment from tissue-culture. We find that mechanical and
      adhesive properties of both cell lines recover quickly (<10 min) after detachment
      using EDTA, while trypsin-detached fibroblasts require >60 min to fully recover.
      Our assay introduced to characterize the recovery of mammalian cells after
      detachment can in future be used to estimate the recovery behavior of other
      adherent cell types.

PMID- 24928444
TI  - Nucleases in homologous recombination as targets for cancer therapy.
AB  - Genomic DNA is constantly challenged from endogenous as well as exogenous
      sources. The DNA damage response (DDR) mechanism has evolved to combat these
      challenges and ensure genomic integrity. In this review, we will focus on repair
      of DNA double-strand breaks (DSB) by homologous recombination and the role of
      several nucleases and other recombination factors as suitable targets for cancer
      therapy. Their inactivation as well as overexpression have been shown to
      sensitize cancer cells by increasing toxicity to DNA-damaging agents and
      radiation or to be responsible for resistance of cancer cells. These factors can
      also be used in targeted cancer therapy by taking advantage of specific genetic
      abnormalities of cancer cells that are not present in normal cells and that
      result in cancer cell lethality. 

PMID- 24928446
TI  - Inhibition of constitutive TNF production is associated with PACAP-mediated
      differentiation in PC12 cells.
AB  - The pituitary adenylate cyclase-activating polypeptide (PACAP) is a trophic
      neuropeptide that promotes cell survival and neuritogenesis in the central and
      peripheral nervous system. Our previous transcriptomic studies revealed the down
      regulation of the cytokine tumor necrosis factor (TNF) during PACAP-induced PC12
      cell differentiation. Here we show that TNF is constitutively expressed in PC12
      cells in a manner dependent on NF-kappaB transcription factor, and that PACAP
      rapidly inhibits TNF expression and secretion. The inhibition occurs through
      suppression of RelB subunit of NF-kappaB, and is likely to prevent the
      deleterious effects of the cytokine on survival and neurite outgrowth during PC12
      cell differentiation. 

PMID- 24928447
TI  - Targeting cytokine networks in KRAS-driven tumorigenesis.
AB  - KRAS is one of the most commonly mutated oncogenes in human tumors, and is
      typically associated with aggressive disease. Despite intensive study and years
      of effort, KRAS has remained refractory to targeted inhibition. Given the
      challenge of inhibiting KRAS directly, current approaches to KRAS targeted
      therapy have involved the disruption of downstream signaling pathways. However,
      combinations of drugs that target RAF/MEK and PI3K/AKT signaling have failed to
      live up to expectations in the clinic. Here we summarize the evidence that the
      cytokine signaling circuitry of KRAS-driven tumors represents an equally
      tractable drug target. Indeed, the incorporation of novel therapeutics that
      disrupts these cytokine signaling networks may hold the key to overcoming this
      seemingly impenetrable treatment barrier. 

PMID- 24928445
TI  - Regulation of autophagy: modulation of the size and number of autophagosomes.
AB  - Autophagy as a conserved degradation and recycling process in eukaryotic cells,
      occurs constitutively, but is induced by stress. A fine regulation of autophagy
      in space, time, and intensity is critical for maintaining normal energy
      homeostasis and metabolism, and to allow for its therapeutic modulation in
      various autophagy-related human diseases. Autophagy activity is regulated in both
      transcriptional and post-translational manners. In this review, we summarize the
      cytosolic regulation of autophagy via its molecular machinery, and nuclear
      regulation by transcription factors. Specifically, we consider Ume6-ATG8 and
      Pho23-ATG9 transcriptional regulation in detail, as examples of how nuclear
      transcription factors and cytosolic machinery cooperate to determine
      autophagosome size and number, which are the two main mechanistic factors through
      which autophagy activity is regulated. 

PMID- 24928448
TI  - Automatic construction of a large-scale and accurate drug-side-effect association
      knowledge base from biomedical literature.
AB  - Systems approaches to studying drug-side-effect (drug-SE) associations are
      emerging as an active research area for drug target discovery, drug
      repositioning, and drug toxicity prediction. However, currently available drug-SE
      association databases are far from being complete. Herein, in an effort to
      increase the data completeness of current drug-SE relationship resources, we
      present an automatic learning approach to accurately extract drug-SE pairs from
      the vast amount of published biomedical literature, a rich knowledge source of
      side effect information for commercial, experimental, and even failed drugs. For
      the text corpus, we used 119,085,682 MEDLINE sentences and their parse trees. We
      used known drug-SE associations derived from US Food and Drug Administration
      (FDA) drug labels as prior knowledge to find relevant sentences and parse trees.
      We extracted syntactic patterns associated with drug-SE pairs from the resulting
      set of parse trees. We developed pattern-ranking algorithms to prioritize drug-SE
      specific patterns. We then selected a set of patterns with both high precisions
      and recalls in order to extract drug-SE pairs from the entire MEDLINE. In total,
      we extracted 38,871 drug-SE pairs from MEDLINE using the learned patterns, the
      majority of which have not been captured in FDA drug labels to date. On average,
      our knowledge-driven pattern-learning approach in extracting drug-SE pairs from
      MEDLINE has achieved a precision of 0.833, a recall of 0.407, and an F1 of 0.545.
      We compared our approach to a support vector machine (SVM)-based machine learning
      and a co-occurrence statistics-based approach. We show that the pattern-learning
      approach is largely complementary to the SVM- and co-occurrence-based approaches
      with significantly higher precision and F1 but lower recall. We demonstrated by
      correlation analysis that the extracted drug side effects correlate positively
      with both drug targets, metabolism, and indications. 

PMID- 24928450
TI  - Persistent sexual, emotional, and cognitive impairment post-finasteride: a survey
      of men reporting symptoms.
AB  - Finasteride is a synthetic 5-alpha reductase inhibitor, which prevents the
      conversion of testosterone to dihydrotestosterone and has been used for more than
      20 years in the treatment of male pattern hair loss. Randomized, controlled
      trials have associated finasteride with both reversible and persistent adverse
      effects. In this pilot study, we sought to characterize sexual and nonsexual
      adverse effects that men reported experiencing at least 3 months after stopping
      the medication. Based on previous research on persistent side effects of
      finasteride, we constructed an Internet survey targeting six domains: physical
      symptoms, sexual libido, ejaculatory disorders, disorders of the penis and
      testes, cognitive symptoms, and psychological symptoms and was e-mailed to
      patients who reported experiencing symptoms of side effects of finasteride.
      Responses from 131 generally healthy men (mean age, 24 years) who had taken
      finasteride for male pattern hair loss was included in the analysis. The most
      notable finding was that adverse effects persisted in each of the domains,
      indicating the possible presence of a "post-finasteride syndrome."

PMID- 24928451
TI  - High estrogen in men after injectable testosterone therapy: the low T experience.
AB  - Testosterone replacement improves quality of life and is aromatized in men in
      adipose tissues to estrogen. Hyperestrogenism is believed to be harmful to male
      sexuality. This is a description of our experience of screening 34,016 men in the
      Low T Centers, of which approximately 50% were converted to treatment. Men were
      treated with injectable testosterone, and we have available data from 2009 to
      2014. The data were extracted from our electronic health record (AdvancedMD) of
      35 Low T Centers across the United States. In all, 7,215 (20.2%) out of the
      34,016 patients had high estradiol levels defined as >=42.6 pg/ml. Estradiol was
      measured using electro-chemiluminescence immunoassay. Of the patients who had
      high estradiol levels, the age distribution was as follows: 132/989 (13.3%) were
      older than 65 years, 3,753/16,955 (22.1%) were between 45 and 65 years;
      2,968/15,857 (18.7%) were between 25 and 44 years, 7/215 (3.3%) were younger than
      25 years. The difference between extreme age groups (<25 and >=65) was
      statistically significant using a chi-square test (p = .013). The correlation
      coefficient of serum estradiol to age was .53, SD = 8.21. It was observed that
      practitioners used aromatase inhibitor and selective estrogen receptor modulator
      to treat symptoms of hyperestrogenism, irrespective of blood estradiol levels.
      Gynecomastia was rarely documented as a reason for the prescription. Our finding
      was that high estradiol levels were not associated with higher rates of low
      libido but established higher rates of documented low libido with those with
      normal or lower estradiol levels. The difference was statistically significant (p
      < .05).

PMID- 24928452
TI  - [Not Available].

PMID- 24928453
TI  - Validation of the self-reported hearing questions in the Irish Longitudinal Study
      on Ageing against the Whispered Voice Test.
AB  - BACKGROUND: Self report questions are often used in population studies to assess
      sensory efficacy and decline. These questions differ in their validity in
      assessing sensory impairment depending on the wording of the question and the
      characteristics of the population. We tested the validity of the self-report
      questions on hearing efficacy (self reported hearing, ability in following a
      conversation, use of a telephone and use of hearing aids) used in The Irish
      Longitudinal Study on Ageing (TILDA). METHODS: We tested sensitivity and
      specificity, positive and negative predictive values of each question against the
      Whispered Voice Test, a relatively easy to administer and cost effective
      alternative to the standard audiometric test. RESULTS: In this population the
      question 'Is your hearing (with or without a hearing appliance)/ Excellent/Very
      Good/Good/Fair/Poor?' showed the best diagnostic value in relation to the other
      questions (sensitivity 55.56% and specificity 94.67%). The question 'Can you use
      a normal telephone?' was deemed ineffective because of a very poor sensitivity
      (5.56%) and was proposed for exclusion from subsequent waves of TILDA.
      CONCLUSIONS: We showed that this validity check was useful to select the
      questions that most effectively assess hearing deficits and provided crucial
      information for the subsequent waves. We argue that longitudinal studies using
      self-reports of sensory efficacy would benefit from a similar check.

PMID- 24928454
TI  - Depletion and biodegradation of hydrocarbons in dispersions and emulsions of the
      Macondo 252 oil generated in an oil-on-seawater mesocosm flume basin.
AB  - Physically and chemically (Corexit 9500) generated Macondo 252 oil dispersions,
      or emulsions (no Corexit), were prepared in an oil-on-seawater mesocosm flume
      basin at 30-32  degrees C, and studies of oil compound depletion performed for up
      to 15 days. The use of Corexit 9500 resulted in smaller median droplet size than
      in a physically generated dispersion. Rapid evaporation of low boiling point oil
      compounds (C?15) appeared in all the experiments. Biodegradation appeared to be
      an important depletion process for compounds with higher boiling points in the
      dispersions, but was negligible in the surface emulsions. While n-alkane
      biodegradation was faster in chemically than in physically dispersed oil no such
      differences were determined for 3- and 4-ring PAH compounds. In the oil
      dispersions prepared by Corexit 9500, increased cell concentrations, reduction in
      bacterial diversity, and a temporary abundance of bacteria containing an alkB
      gene were associated with oil biodegradation.

PMID- 24928455
TI  - Capacitive deionization of seawater effected by nano Ag and Ag@C on graphene.
AB  - Drinking water shortage has become worse in recent decades. A new capacitive
      deionization (CDI) method for increasing water supplies through the effective
      desalination of seawater has been developed. Silver as nano Ag and Ag@C which was
      prepared by carbonization of the Ag(+)-beta-cyclodextrin complex at 573 K for 30
      min can add the antimicrobial function into the CDI process. The Ag@C and Ag
      nanoparticles dispersed on reduced graphene oxide (Ag@C/rGO and nano Ag/rGO) were
      used as the CDI electrodes. The nano Ag/rGO and Ag@C/rGO electrodes can reduce
      the charging resistant, and enhance the electrosorption capability. Better CDI
      efficiencies with the nano Ag/rGO and Ag@C/rGO electrodes can therefore be
      obtained. When reversed the voltage, the electrodes can be recovered up to 90%
      within 5 min. This work presents the feasibility for the nano Ag and Ag@C on rGO
      electrodes applied in CDI process to produce drinking water from seawater or
      saline water.

PMID- 24928456
TI  - Sulfonamide antibiotics in the Northern Yellow Sea are related to resistant
      bacteria: implications for antibiotic resistance genes.
AB  - Antibiotic resistance gene (ARG) residues and the mode of transmission in marine
      environments remain unclear. The sulfonamide (SAs) concentrations, different
      genes and total bacterial abundance in seawater and sediment of the Northern
      Yellow Sea were analyzed. Results showed the genes sul I and sul II were present
      at relatively high concentrations in all samples, whereas the gene sul III was
      detected fewer. The ARGs concentrations in the sediment were 10(3) times higher
      than those in water, which indicated sediment was essential ARG reservoir.
      Statistical analysis revealed the total antibiotic concentration was positively
      correlated with the relative abundance of the gene sul I and sul II. The relative
      abundances of the gene sul I and the gene sul II were also correlated positively
      with those of the gene int1. This correlation demonstrated that SAs exerted
      selective pressure on these ARGs, whereas the gene int1 could be implicated in
      the propagation of the genes sul I and sul II in marine environments. 

PMID- 24928457
TI  - Triclosan causes toxic effects to algae in marine biofilms, but does not inhibit
      the metabolic activity of marine biofilm bacteria.
AB  - Effects of the antimicrobial agent triclosan to natural periphyton communities
      (biofilms, comprising primarily microalgae and bacteria) were assessed in two
      independent experiments during spring and summer. For that purpose a semi-static
      test system was used in which periphyton was exposed to a concentration range of
      5-9054 nmol/L triclosan. Effects on algae were analyzed as content and
      composition of photosynthetic pigments. The corresponding EC50 values were 39.25
      and 302.45 nmol/L for the spring and summer experiment, respectively. Effects on
      periphytic bacteria were assessed as effects on carbon utilization patterns,
      using Biolog Ecoplates. No inhibition of either total carbon utilization or
      functional diversity was observed, indicating a pronounced triclosan tolerance of
      the marine bacteria. In contrast, a small stimulation of the total carbon
      utilization was observed at triclosan concentrations exceeding 100 nmol/L.

PMID- 24928458
TI  - Ballast water: a threat to the Amazon Basin.
AB  - Ballast water exchange (BWE) is the most efficient measure to control the
      invasion of exotic species from ships. This procedure is being used for merchant
      ships in national and international voyages. The ballast water (BW) salinity is
      the main parameter to evaluate the efficacy of the mid-ocean ballast water
      exchange. The vessels must report to the Port State Control (PSC), via ballast
      water report (BWR), where and how the mid-ocean BWE was performed. This measure
      allows the PSC to analyze this information before the ship arrives at the port,
      and to decide whether or not it should berth. Ship BW reporting forms were
      collected from the Captaincy of Santana and some ships were visited near the Port
      of Santana, located in Macapa (Amazon River), to evaluate the BW quality onboard.
      We evaluated data submitted in these BWR forms and concluded that the BWE
      efficacy might be compromised, because data contained in these BWR indicate that
      some ships did not change their BW. We found mistakes in filling the BWR forms
      and lack of information. Moreover, these ships had discharged BW with high level
      of salinity, Escherichia coli and total coliforms into the Amazon River. We
      concluded that the authorities of the Amazon Region need to develop more
      efficient proceedings to evaluate the ballast water reporting forms and BW
      quality, as there is potential risk of future invasion of exotic species in
      Brazilian ports. 

PMID- 24928459
TI  - Complete penile amputation during ritual neonatal circumcision and successful
      replantation using postoperative leech therapy.
AB  - Circumcision is the most common surgical procedure in males in the United States,
      and minor complications are not uncommon. Major complications like partial penile
      amputations have been reported with successful replantation. Complete penile
      amputations in adult males have been described, and successful replantation has
      been reported with increasing success. We report a case of complete penile
      amputation at the penopubic junction using a Mogen clamp in a 7-day-old neonate
      with replantation using postoperative leech therapy. To our knowledge this is the
      first time leech therapy has been used postoperatively for neonatal penile
      amputation. 

PMID- 24928460
TI  - Editorial comment.

PMID- 24928461
TI  - Reply: To PMID 24928460.

PMID- 24928462
TI  - Diagnostic and management approaches to pediatric and adolescent varicocele: a
      survey of pediatric urologists.
AB  - OBJECTIVE: To assess current diagnosis and management of adolescent varicoceles
      by pediatric urologists. METHODS: Online questionnaires assessing diagnosis and
      management approaches to pediatric and adolescent varicocele were distributed
      electronically to a national listing of pediatric urologists. RESULTS: Of 242
      pediatric urologists surveyed, 131 (54%) responded to the survey. Only 3% of
      respondents operate on varicoceles at diagnosis, whereas 14% observe, and 83%
      base treatment on further indications. Varicocelectomy is most commonly performed
      for decreased ipsilateral testicular size (96%), testicular pain (79%), and
      altered semen analysis parameters (39%), with the mean age for varicocelectomy
      being 12.5 +/- 3.1 years. Most physicians use ultrasonography (US) or Doppler US
      to aid in the diagnosis of varicoceles, and half of physicians would not repair
      incidental findings of varicocele on US. In an otherwise asymptomatic patient
      with a varicocele, 28% of physicians would consider varicocelectomy depending on
      varicocele grade. The most common surgical approaches to varicocelectomy were
      laparascopic (38%), subinguinal microsurgical (28%), inguinal (14%), and
      retroperitoneal (13%), and most physicians used loupes for these procedures. The
      most common complication experienced after adolescent varicocelectomy was
      hydrocele followed by hematoma, testicular atrophy, chronic pain, paresthesia,
      and varicocele recurrence or persistence. Only 58% of physicians had follow-up
      data on their varicocele patients, and 89% did not know whether patients
      developed infertility. Of patients who developed infertility, 39% had undergone
      varicocele repair. CONCLUSION: Significant variation in diagnostic approaches,
      decision to treat, and operative approaches exists among pediatric urologists,
      and combined with a dearth of objective data, limits development of management
      guidelines.

PMID- 24928463
TI  - A useful tip for open laparoscopy.

PMID- 24928464
TI  - [High blood pressure and physical exercise].
AB  - High blood pressure is a frequent pathology with many cardiovascular
      complications. As highlighted in guidelines, the therapeutic management of
      hypertension relies on non-pharmacological measures, which are diet and regular
      physical activity, but both patients and physicians are reluctant to physical
      activity prescription. To acquire the conviction that physical activity is
      beneficial, necessary and possible, we can take into account some fundamental and
      clinical studies, as well as the feedback of our clinical practice. Physical
      inactivity is a major risk factor for cardiovascular morbidity and mortality, and
      hypertension contributes to increase this risk. Conversely, regular practice of
      physical activity decreases very significantly the risk by up to 60%. The acute
      blood pressure changes during exercise and post-exercise hypotension differs
      according to the dynamic component (endurance or aerobic and/or strength
      exercises), but the repetition of the sessions leads to the chronic hypotensive
      benefit of physical activity. Moreover, physical activity prescription must take
      into account the assessment of global cardiovascular risk, the control of the
      hypertension, and the opportunities and desires of the patient in order to
      promote good adherence and beneficial lifestyle change. 

PMID- 24928465
TI  - [Medical practice in support of hypertension as risk factor kidney in general
      medical practice, and primary prevention in children in schools, and the pregnant
      woman in Annaba (Algeria)].
AB  - OBJECTIVE: To study medical practice in the management of hypertension as a
      factor in renal risk in general medical practice and primary prevention in
      children at school, and pregnant women under prenatal monitoring. METHOD: The
      longitudinal study, observational over a year, focused on medical practice in
      schools, maternal health and medical practice among 100 physicians (general
      practitioner and specialist practitioner) in Annaba (Algeria). RESULTS: In
      children in schools, measurement of blood pressure is never done on the grounds
      because this gesture is considered unnecessary in 100% of cases. In pregnant
      women, the measurement of blood pressure is not performed in more than 26% of
      pregnant women because it is deemed unnecessary by the midwife in 89% of pregnant
      women and default material in 11% of they. In current medical practice, 69% of
      doctors routinely take blood pressure. For the rest, represented mainly by
      specialists, it is the patient who does not justify. Sixty-two percent of
      physicians, that is hypertension, above 140/90mmHg, and 15% of physicians that is
      hypertension, above 145/95mmHg. Among the physicians, 58.7% did not use urinary
      strip, either, because they think that this review should be done in a laboratory
      (64.8%), or because the urinary strip are not available at even consulting
      (35.2%). CONCLUSION: Inadequacies in the coverage (care) of the HTA are real.
      Their effects on the progress of prevalence of the renal insufficiency chronic
      terminal treated are possibly important.

PMID- 24928466
TI  - Significant impairment of health-related quality of life in mainland Chinese
      patients with chronic hepatitis B: a cross-sectional survey with pair-matched
      healthy controls.
AB  - OBJECTIVE: Few studies have evaluated health-related quality of life (HRQoL) of
      patients with chronic hepatitis B (CHB) in mainland China. We aimed at
      characterizing the impact of CHB on HRQoL in mainland Chinese and finding out
      factors associated with HRQoL. METHODS: 460 CHB patients (323 with CHB only, 54
      with compensated cirrhosis and 83 with decompensated cirrhosis) and 460 pair
      matched healthy controls were recruited in Xi'an city. They answered a structured
      questionnaire including the Short Form 36 version 2 (SF-36v2), the Chronic Liver
      Disease Questionnaire (CLDQ) (only for patients), and questions on socio
      demographic and clinical characteristics. A blood sample was collected from each
      of patients for liver function tests. SF-36v2 scores were compared between
      patients and controls overall and by groups by paired-samples t-test, and CLDQ
      scores and paired differences of SF-36v2 scores were compared among three patient
      groups by one-way ANOVA or Kruskal-Wallis test. Multi-variable linear regression
      analyses were performed to identify determinants of HRQoL in patients. RESULTS:
      Patients, overall and by groups had significantly lower SF-36v2 scores than
      controls on all summaries and domains, with differences higher than the suggested
      minimally important difference values. Both the SF-36v2 and the CLDQ showed that
      HRQoL of patients with cirrhosis further deteriorated, but compensated and
      decompensated cirrhosis patients had similar total HRQoL impairments. The
      gradually increasing impairment with disease progression was confirmed only on
      physical components. Impaired liver function and currently taken anti-viral
      treatment were associated with lower HRQoL. Education attainment and annual per
      capita household income had a positive effect on HRQoL. CONCLUSIONS: Mainland
      Chinese CHB patients suffered significant HRQoL impairment on all health
      dimensions, and the impairment reached a high level on mental health at initial
      stage of illness and increased gradually on physical health with disease
      progression. Attention should be paid to the reduction of patients' treatment
      cost burden and the provision of early health education accompanied with proper
      treatments.

PMID- 24928467
TI  - Review of Guidance for Health Care Ethics Committees.

PMID- 24928468
TI  - Red blood cell alloimmunization mitigation strategies.
AB  - Hemolytic transfusion reactions due to red blood cell (RBC) alloantibodies are a
      leading cause of transfusion-associated death. In addition to reported deaths,
      RBC alloantibodies also cause significant morbidity in the form of delayed
      hemolytic transfusion reactions. These alloantibodies may also cause morbidity in
      the form of anemia, with compatible RBC units at times being unable to be located
      for highly alloimmunized patients, or in the form of hemolytic disease of the
      newborn. Thus, preventing RBC alloantibodies from developing in the first place,
      or mitigating the dangers of existing RBC alloantibodies, would decrease
      transfusion-associated morbidity and mortality. A number of human studies have
      evaluated the impact on RBC alloimmunization rates of providing partially
      phenotypically or genotypically matched RBCs for transfusion, and a number of
      animal studies have evaluated the impact of single variables on RBC
      alloimmunization. The goal of this review is to take a comprehensive look at
      existing human and animal data on RBC alloimmunization, focusing on strategies
      that may mitigate this serious hazard of transfusion. Potential factors that
      impact initial RBC alloimmunization, on both the donor and recipient sides, will
      be discussed. These factors include, but are not limited to, exposure to the
      antigen and an ability of the recipient's immune system to present that antigen.
      Beyond these basic factors, coexisting "danger signals," which may come from the
      donor unit itself or which may be present in the recipient, also likely play a
      role in determining which transfusion recipients may become alloimmunized after
      RBC antigen exposure. In addition, to better understanding factors that influence
      the development of RBC alloantibodies, this review will also briefly discuss
      strategies to decrease the dangers of existing RBC alloantibodies. 

PMID- 24928469
TI  - Circulating microRNA profiling in patients with advanced non-squamous NSCLC
      receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at
      progression (SAKK 19/05).
AB  - OBJECTIVES: Molecular subclassification of non small-cell lung cancer (NSCLC) is
      essential to improve clinical outcome. This study assessed the prognostic and
      predictive value of circulating micro-RNA (miRNA) in patients with non-squamous
      NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research)
      trial 19/05, receiving uniform treatment with first-line bevacizumab and
      erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND
      METHODS: Fifty patients with baseline and 24 h blood samples were included from
      SAKK 19/05. The primary study endpoint was to identify prognostic (overall
      survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA
      8x60K microarrays, each glass slide formatted with eight high-definition 60K
      arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data
      preprocessing included quantile normalization using robust multi-array average
      (RMA) algorithm. Prognostic and predictive miRNA expression profiles were
      identified by Spearman's rank correlation test (percentage tumor shrinkage) or
      log-rank testing (for time-to-event endpoints). RESULTS: Data preprocessing kept
      49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly
      associated with OS, with hsa-miR-29a being the strongest prognostic marker
      (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a
      significantly lower survival at 10 months compared to patients with a low
      expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542
      5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to
      perturbations according to jackknife cross-validation on their HR for OS. The
      respective principal component analysis (PCA) defined a meta-miRNA signature
      including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82).
      CONCLUSION: Cell-free circulating miRNA-profiling successfully identified a
      highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC.
      Circulating miRNA profiling should further be validated in external cohorts for
      the selection and monitoring of systemic treatment in patients with advanced
      NSCLC.

PMID- 24928470
TI  - Motion of the shoulder complex in individuals with isolated acromioclavicular
      osteoarthritis and associated with rotator cuff dysfunction: part 2 - muscle
      activity.
AB  - This study aimed to compare muscle activity in individuals with isolated
      acromioclavicular osteoarthritis (ACO), ACO associated with rotator cuff disease
      (ACO+RCD), and controls. Seventy-four participants (23 isolated ACO, 25 ACO+RCD,
      26 controls) took part in this study. Disability was assessed with the
      Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Muscle activity
      of the upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and
      anterior deltoid (AD) was collected during arm elevation in the sagittal and
      scapular planes. Pain during motion was assessed with the numerical pain rating
      scale. Analysis of the DASH, pain and kinematics were reported in part 1 of this
      study. For each muscle, separate 2-way linear mixed-model ANOVAs were performed
      to compare groups. ACO+RCD group had more UT and AD activity than the the
      isolated ACO and control other groups, more AD activity than the isolated ACO
      group during the ascending phase, and more AD activity than the ACO and control
      groups during the descending phase in both planes. Isolated ACO group had less SA
      activity than the control group only in the sagittal plane. Alterations in
      shoulder muscle activity are present in individuals with isolated ACO and with
      ACO+RCD and should be considered in rehabilitation. 

PMID- 24928471
TI  - Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma
      leakage in patients with acute dengue virus infection.
AB  - BACKGROUND: Endothelial cell dysfunction is believed to play an important role in
      the pathogenesis of plasma leakage in patients with acute dengue virus (DENV)
      infection. Several factors, produced by activated endothelial cells, have been
      associated with plasma leakage or severe disease in patients with infectious
      diseases. OBJECTIVES: The aim of this study was to investigate which of these
      markers could serve as a surrogate marker for the occurrence of plasma leakage in
      patients with acute DENV infection. STUDY DESIGN: A case-control study was
      performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage
      was detected with X-ray and/or ultrasound examination at admission. Serum levels
      of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2,
      MMP-9, TIMP-1 and TIMP-2 were determined using commercially available ELISAs.
      RESULTS: Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased
      levels of soluble VEGFR-2 were significantly associated with the occurrence of
      plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2
      and soluble VEGFR-2 were strongly associated with clinical apparent vascular
      leakage. CONCLUSION: Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate
      markers for the occurrence of plasma leakage in patients with acute DENV
      infection.

PMID- 24928472
TI  - Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA
      deposition based upon heterogeneity in the composition of immune complexes in IgA
      nephropathy.
AB  - BACKGROUND: Although serum under-O-glycosylated IgA1 in IgA nephropathy (IgAN)
      patients may deposit more preferentially in glomeruli than heavily-O-glycosylated
      IgA1, the relationship between the glomerular IgA deposition level and the O
      glycan profiles of serum IgA1 remains obscure. METHODS: Serum total under-O
      glycosylated IgA1 levels were quantified in 32 IgAN patients by an enzyme-linked
      immunosorbent assay (ELISA) with Helix aspersa (HAA) lectin. Serum under-O
      glycosylated polymeric IgA1 (pIgA1) was selectively measured by an original
      method using mouse Fcalpha/MU receptor (mFcalpha/MUR) transfectant and flow
      cytometry (pIgA1 trap). The percentage area of IgA deposition in the whole
      glomeruli (Area-IgA) was quantified by image analysis on the immunofluorescence
      of biopsy specimens. Correlations were assessed between the Area-IgA and data
      from HAA-ELISA or pIgA1 trap. The relationships between clinical parameters and
      data from HAA-ELISA or pIgA1 trap were analyzed by data mining approach. RESULTS:
      While the under-O-glycosylated IgA1 levels in IgAN patients were significantly
      higher than those in healthy controls when measured (p<0.05), there was no
      significant difference in under-O-glycosylated pIgA1. There was neither a
      correlation observed between the data from HAA-ELISA and pIgA1 trap (r2=0.09) in
      the IgAN patients (r2=0.005) nor was there a linear correlation between Area-IgA
      and data from HAA-ELISA or the pIgA1 trap (r2=0.005, 0.03, respectively). Contour
      plots of clinical parameters versus data from HAA-ELISA and the pIgA1 trap
      revealed that patients with a high score in each clinical parameter concentrated
      in specific areas, showing that patients with specific O-glycan profiles of IgA1
      have similar clinical parameters. A decision tree analysis suggested that
      dominant immune complexes in glomeruli were consisted of: 1) IgA1-IgG and
      complements, 2) pIgA1 and complements, and 3) monomeric IgA1-IgA or aggregated
      monomeric IgA1. CONCLUSIONS: Serum under-O-glycosylated IgA1 levels are not
      correlated with glomerular IgA deposition based upon heterogeneity in the
      composition of glomerular immune complexes in IgAN patients.

PMID- 24928473
TI  - Maintenance and manipulation of object sequences in working memory: a lifespan
      study.
AB  - Many studied reported that working memory components receive remarkable changes
      during lifespan. In order to better investigate this, we evaluated working memory
      components on human subjects belonging to five groups (10 subjects each) at
      different ages 6, 8 and 10 years old, young adult (age) and old adult (age). Our
      pattern of results shows a major transition in object sequence manipulation
      performance between ages 8 and 10 years. If related to young adults results, both
      10-year-old children and old adults differed in accuracy and RT (specificare cosa
      significa) in both maintenance and manipulation conditions. In particular, young
      adults and old adults differ in RTs in the manipulation condition. Our results
      also suggest that a change in response strategy from 6 to 8 years of age, to
      prioritize accuracy may be present. Our findings appear consistent with recent
      neuroscientific findings, and lead to novel predictions.

PMID- 24928474
TI  - Breakfast patterns among low-income, ethnically-diverse 4th-6th grade children in
      an urban area.
AB  - BACKGROUND: Increasing school breakfast participation has been advocated as a
      method to prevent childhood obesity. However, little is known about children's
      breakfast patterns outside of school (e.g., home, corner store). Policies that
      increase school breakfast participation without an understanding of children's
      breakfast habits outside of school may result in children consuming multiple
      breakfasts and may undermine efforts to prevent obesity. The aim of the current
      study was to describe morning food and drink consumption patterns among low
      income, urban children and their associations with relative weight. METHODS: A
      cross-sectional analysis was conducted of data obtained from 651 4th-6th graders
      (51.7% female, 61.2% African American, 10.7 years) in 2012. Students completed
      surveys at school that included all foods eaten and their locations that morning.
      Height and weight were measured by trained research staff. RESULTS: On the day
      surveyed, 12.4% of youth reported not eating breakfast, 49.8% reported eating one
      breakfast, 25.5% reported eating two breakfasts, and 12.3% reported eating three
      or more breakfasts. The number of breakfasts consumed and BMI percentile showed a
      significant curvilinear relationship, with higher mean BMI percentiles observed
      among children who did not consume any breakfast and those who consumed >= 3
      breakfasts. Sixth graders were significantly less likely to have consumed
      breakfast compared to younger children. A greater proportion of obese youth had
      no breakfast (18.0%) compared to healthy weight (10.1%) and overweight youth
      (10.7%, p = .01). CONCLUSIONS: When promoting school breakfast, policies will
      need to be mindful of both over- and under-consumption to effectively address
      childhood obesity and food insecurity. CLINICAL TRIAL REGISTRATION: NCT01924130
      from http://clinicaltrials.gov/.

PMID- 24928475
TI  - Steroidal saponins from Dioscorea preussii.
AB  - Three new steroidal saponins, named diospreussinosides A-C (1-3), along with two
      known ones (4, 5) were isolated from rhizomes of Dioscorea preussii. Their
      structures were elucidated mainly by 1D and 2D NMR spectroscopic analysis and
      mass spectrometry as (25S)-17alpha,25-dihydroxyspirost-5-en-3beta-yl-O-alpha-L
      rhamnopyranosyl-(1->4)-alpha-L-rhamnopyranosyl-(1->4)-beta-D-glucopyranoside (1),
      (25S)-17alpha,25-dihydroxyspirost-5-en-3beta-yl-O-alpha-L-rhamnopyranosyl-(1->4)
      alpha-L-rhamnopyranosyl-(1->4)-[alpha-L-rhamnopyranosyl-(1->2)]-beta-D
      glucopyranoside (2), and (24S,25R)-17alpha,24,25-trihydroxyspirost-5-en-3beta-yl
      O-alpha-L-rhamnopyranosyl-(1->4)-alpha-L-rhamnopyranosyl-(1->4)-[alpha-L
      rhamnopyranosyl-(1->2)]-beta-D-glucopyranoside (3). The spirostane-type skeleton
      of compound 3 possessing an unusual dihydroxylation pattern on the F-ring is
      reported for the first time. Cytotoxicity of compounds 2-5 was evaluated against
      two human colon carcinoma cell lines (HT-29 and HCT 116).

PMID- 24928476
TI  - Scrotal pop off in a congenital anterior urethral diverticulum.
AB  - INTRODUCTION AND OBJECTIVE: Congenital anterior urethral diverticulum is a rare
      entity. This teaching video shows the scrotal pop-off mechanism for an anterior
      urethral diverticulum and the unique voiding pattern of a boy who empties his
      bladder by compression of his scrotum. The findings during urethroscopy and open
      reconstruction are also demonstrated. PATIENT AND METHODS: A four-year-old boy
      presented to the clinic with a poor urinary stream and scrotal swelling during
      voiding. Physical examination during voiding revealed a dumbbell-shaped anterior
      urethral diverticulum with scrotal pop off and preserved renal function. RESULTS:
      Open excision of the scrotal part of diverticulum was performed. Urethroplasty
      was conducted using a de-epithelialised diverticular wall flap from the
      penobulbar urethra. On follow up the boy voided with a good flow and resolution
      of symptoms. CONCLUSION: Scrotal pop off with completion of voiding by manual
      compression of the diverticulum may preserve bladder and renal function. The
      preferred treatment of anterior urethral diverticulum is open excision of the
      diverticulum and reconstruction. The wall of the diverticulum may be used to
      reinforce the repair ventrally, where the corpus spongiosum is deficient.

PMID- 24928477
TI  - Hair ethyl glucuronide as a biomarker of alcohol consumption in alcohol-dependent
      patients: role of gender differences.
AB  - BACKGROUND: Ethyl glucuronide (EtG) is a minor alcohol metabolite that
      accumulates in hair and is proposed as a stable marker for the detection of
      chronic and excessive alcohol consumption above a cut-off level of 30pg/mg hair.
      A correlation between drinking behavior and EtG hair concentrations is observed,
      but large variability exists. AIMS: To investigate the correlation between
      alcohol consumption and hair EtG concentrations in alcohol dependent patients,
      and the effect of gender differences as a factor for the variability on this
      correlation. METHODS: EtG was measured by gas chromatography coupled to mass
      spectrometry in the hairs (first 3cm) of 36 alcohol dependent patients (25
      males/11 females) starting and alcohol detoxification program. Factors that
      possibly influence EtG content in hair (except age and gender) were excluded.
      Detailed retrospective alcohol consumption was obtained over the last 3 months
      using the Timeline Follow Back interview. RESULTS: Median total alcohol
      consumption over 3 months was 13,050g pure alcohol (range 60-650g/day). Hair EtG
      concentrations varied between 32 and 662pg/mg. There was a statistically
      significant linear and positive correlation between hair EtG and amounts of
      alcohol consumed (Pearson r=0.83; p<0.001), in both males (Pearson r=0.83;
      p<0.001) and females (Pearson r=0.76; p=0.007). CONCLUSIONS: There is a linear
      correlation, with no significant effect of gender, between hair EtG
      concentrations and amounts of alcohol consumed in alcohol-dependent individuals.
      Analysis of EtG in hair can be applied to estimate retrospective alcohol
      consumption in both male and female alcohol dependent subjects using the same cut
      off.

PMID- 24928478
TI  - The role of participants' self-selected future smoking goals in adolescent
      smoking cessation interventions.
AB  - BACKGROUND: There is an implicit assumption that abstinence is the treatment goal
      of young smokers that deliberately participate in cessation interventions, but
      this may not always be the case. To gain information on subgroups of adolescent
      intervention participants, we compare participants who want to achieve smoking
      abstinence (Abst) with those stating a non-abstinence future smoking goal
      (NAbst), with regard to baseline characteristics, reasons for participation, quit
      motivation, retention, goal attainment, and smoking abstinence. METHODS: The
      sample consisted of 202 adolescent smokers (49.5% female). At baseline, 118
      (58.4%) indicated abstinence as future smoking goal and 84 (41.6%) indicated non
      abstinence. All participants received a behavioral smoking cessation
      intervention. Assessments took place before, during, and after treatment, and at
      6-month follow-up. Regression analyses were conducted. RESULTS: Abst and NAbst
      participants reported similar baseline characteristics. Abst participants,
      however, were more likely to report a previous quit attempt and indicated a
      higher quit motivation before and during treatment. Abst participants were more
      likely to participate based on own initiative and NAbst participants because of
      participating friends. Both groups attended a similar number of intervention
      sessions and were equally likely to attain their self-selected smoking goal.
      However, more Abst participants reported a successful quit attempt during
      treatment and abstinence at post-treatment and follow-up. CONCLUSIONS: NAbst
      participants may represent a substantial subgroup in smoking cessation
      interventions for adolescents. Results indicate that future smoking goals can
      influence treatment outcomes. NAbst participants in treatment may benefit from
      additional information on the negative health consequences of light smoking.

PMID- 24928479
TI  - Treatment with modafinil and escitalopram, alone and in combination, on cocaine
      induced effects: a randomized, double blind, placebo-controlled human laboratory
      study.
AB  - BACKGROUND: Concurrent administration of dopamine and serotonin reuptake
      inhibitors reduces cocaine self-administration in monkeys. Consonant with this,
      clinical trials assessing modafinil and selective serotonin reuptake inhibitors
      alone show some efficacy as potential pharmacotherapies for cocaine dependence.
      We hypothesized that combining modafinil with escitalopram would attenuate the
      euphoric effects of cocaine to a greater degree than modafinil alone. METHODS: In
      a randomized, double blind, parallel groups design participants received either
      placebo (0mg/day; n=16), modafinil (200mg/day; n=16), escitalopram (20mg/day;
      n=17), or modafinil+escitalopram (200+20mg/day; n=15) for 5 days. On day 5,
      during separate sessions participants received an intravenous sample of cocaine
      (0 or 20mg; randomized) and five $1 bills. Participants rated the subjective
      effects of the infusions and subsequently made choices to either return $1 and
      receive another infusion or keep $1 and receive no infusion. RESULTS: Compared to
      saline, cocaine (20mg) significantly (p<=0.008) increased most ratings, including
      "good effects", "stimulated", and "high". Relative to placebo, modafinil
      significantly (p<=0.007) attenuated subject-rated increases of "any drug effect",
      "high", "good effects", and "stimulated" produced by cocaine. Compared to saline,
      participants chose cocaine infusions significantly more; however, no treatment
      significantly reduced choices for cocaine infusions. Escitalopram did not enhance
      the efficacy of modafinil to reduce any measure. CONCLUSIONS: Modafinil
      attenuated many positive subjective effects produced by cocaine; however,
      escitalopram combined with modafinil did not enhance the efficacy of modafinil to
      reduce cocaine effects.

PMID- 24928480
TI  - Frequent marijuana use is associated with greater nicotine addiction in
      adolescent smokers.
AB  - BACKGROUND: Marijuana and tobacco are the substances used most commonly by
      adolescents and co-occurring use is common. Use of one substance may potentiate
      the addictive properties of the other. The current study examined the severity of
      nicotine addiction among teen smokers as a function of co-occurring marijuana
      use. METHODS: Participants were 165 adolescents (13-17 years old) who reported
      smoking at least 1 cigarette per day (CPD) in the past 30 days. General linear
      models examined the association of marijuana use with multiple measures of
      nicotine addiction including the Modified Fagerstrom Tolerance Questionnaire
      (mFTQ), Hooked on Nicotine Checklist (HONC), ICD-10, and the Nicotine Dependence
      Syndrome Scale (NDSS). RESULTS: The adolescent sample (mean age=16.1 years,
      SD=0.95) averaged 3.0 CPD (SD=3.0) for 1.98 years (SD=1.5). Most (79.5%) also
      smoked marijuana in the past 30 days. In models controlling for age, daily
      smoking status, and years of tobacco smoking, frequency of marijuana use
      accounted for 25-44% of the variance for all four measures of adolescent nicotine
      dependence. CONCLUSIONS: Marijuana use was associated with greater reported
      nicotine addiction among adolescent smokers. The findings suggest a role of
      marijuana in potentiating nicotine addiction and underscore the need for
      treatments that address both smoked substances.

PMID- 24928482
TI  - The European Association for Cancer Education (EACE) 2014 meeting report.

PMID- 24928481
TI  - Cervical Cancer Prevention Knowledge and Abnormal Pap Test Experiences Among
      Women Living with HIV/AIDS.
AB  - Cervical cancer prevention knowledge deficits persist among women living with
      HIV/AIDS (WLHA) despite increased risk of developing cervical dysplasia/cancer.
      We examined associations between WLHA's cervical cancer prevention knowledge and
      abnormal Pap test history. We recruited 145 urban and rural WLHA from Ryan White
      funded clinics and AIDS service organizations located in the southeastern USA
      between March 2011 and April 2012. For this analysis, women who reported a
      history of cervical cancer (n = 3) or had a complete hysterectomy (n = 14) and
      observations with missing data (n = 22) were excluded. Stata/IC 13 was used to
      perform cross-tabulations and chi-squared tests. Our sample included 106
      predominantly non-Hispanic Black (92%) WLHA. Mean age was 46.3 +/- 10.9 years.
      Half (50%) had <= high school education. One third (37%) had low health literacy.
      The majority (83 %) had a Pap test <1 year ago, and 84 % knew that WLHA should
      have a Pap test every year, once two tests are normal. Many (68%) have had an
      abnormal Pap test. Abnormal Pap test follow-up care knowledge varied. While 86%
      knew follow-up care could include a repeat Pap test, only 56% knew this could
      also include an HPV test. Significantly, more women who had an abnormal Pap test
      knew follow-up care could include a biopsy (p = 0.001). For WLHA to make
      informed/shared decisions about their cervical health, they need to be
      knowledgeable about cervical cancer care options across the cancer control
      continuum. Providing WLHA with prevention knowledge beyond screening
      recommendations seems warranted given their increased risk of developing cervical
      dysplasia/neoplasia.

PMID- 24928483
TI  - Influence of cardioversion on asymptomatic cerebral lesions following atrial
      fibrillation ablation.
AB  - PURPOSE: Asymptomatic cerebral lesions detected by diffusion-weighted magnetic
      resonance imaging (MRI) following atrial fibrillation (AF) ablation were reported
      in recent years. It was reported that cardioversion during the procedure of AF
      ablation was one independent risk factor of asymptomatic cerebral lesions.
      However, in some studies, the similar association between asymptomatic cerebral
      lesions and intraprocedural cardioversion was not observed. Given the
      inconsistent results, we did a meta-analysis to explore the influence of
      intraprocedural cardioversion on the asymptomatic cerebral lesions detected by
      MRI following AF ablation. METHODS: Studies exploring the association between
      cardioversion during AF ablation and asymptomatic cerebral lesions following AF
      ablation were systematically searched in PubMed, Web of Science and the Cochrane
      Library Databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      pooled. Subgroup and sensitivity analyses were performed to explore the source of
      heterogeneity. RESULTS: Nine studies involving 813 participants were included in
      the present meta-analysis. When we pooled data from nine studies using fixed
      effects model, we found cardioversion during the procedure significantly
      increased the risk of asymptomatic cerebral lesions detected by MRI following AF
      ablation (pooled OR = 1.793, 95% CI 1.201-2.678, I (2) = 38.8%, P heterogeneity =
      0.109). CONCLUSIONS: Cardioversion during AF ablation significantly increased the
      risk of asymptomatic cerebral lesions on MRI following the procedure. Additional
      studies are required to further verify the association.

PMID- 24928484
TI  - MediGuide-impact on catheter ablation techniques and workflow.
AB  - Since the introduction of percutaneous intervention in modern medical science,
      specifically cardiovascular medicine fluoroscopy has remained the gold standard
      for navigation inside the cardiac structures. As the complexity of the procedures
      continue to increase with advances in interventional electrophysiology, the
      procedural times and fluoroscopy times have proportionately increased and the
      risks of radiation exposure both to the patients as well as the operator continue
      to rise. 3D electroanatomic mapping systems have to some extent complemented
      fluoroscopic imaging in improving catheter navigation and forming a solid
      platform for exploring the electroanatomic details of the target substrate. The
      3D mapping systems are still limited as they continue to be static
      representations of a dynamic heart without being completely integrated with
      fluoroscopy. The field needed a technological solution that could add a dynamic
      positioning system that can be successfully incorporated into fluoroscopic
      imaging as well as electroanatomic imaging modalities. MediGuide is one such
      innovative technology that exploits the geo-positioning system principles. It
      employs a transmitter mounted on the X-ray panel that emits an electromagnetic
      field within which sensor-equipped diagnostic and ablation catheters are tracked
      within prerecorded fluoroscopic images. MediGuide is also integrated with NavX
      mapping system and helps in developing better 3D images by field scaling-a
      process that reduces field distortions that occur from impedance mapping alone.
      In this review, we discuss about the principle of MediGuide technology, the
      catheter ablation techniques, and the workflow in the EP lab for different
      procedures. 

PMID- 24928485
TI  - Outflow tract premature ventricular depolarizations after atrial fibrillation
      ablation may reflect autonomic influences.
AB  - PURPOSE: Autonomic modulation following catheter ablation of atrial fibrillation
      may promote the development of catecholamine-sensitive arrhythmias, such as
      outflow tract (OT) ventricular premature depolarizations (VPDs). The purpose of
      this study was to determine the incidence and prognostic significance of OT VPDs
      occurring in patients after atrial fibrillation (AF) ablation. METHODS: We
      prospectively examined 53 consecutive patients undergoing wide-area
      circumferential antral pulmonary vein (PV) isolation; no patients had evidence of
      OT VPDs on 24 h of preprocedural telemetry monitoring. Cases (OT+) had
      postprocedure telemetry monitoring with >30 continuous beats or >3/min OT VPDs.
      Clinical follow-up included transtelephonic monitoring at 6 weeks, 6 months, and
      1 year. RESULTS: The incidence of OT VPDs in this population was 11% (6/53).
      There was no difference in AF recurrence at 1 year between those with or without
      OT VPDs (17 vs 28%, p = 0.6). There was a strong association with higher
      immediate postprocedure heart rate (HR) in OT+ compared to OT- patients (86 vs
      76, p = 0.03); this difference persisted at 1 year (79 vs 60, p < 0.01). OT VPDs
      resolved in 5/6 of the OT+ patients over the 1-year follow-up. In a multivariable
      linear regression model, OT VPDs were associated with higher HR (odds ratio (OR)
      1.14 [1.10-1.18], p < 0.001) despite adjustment for medication dose. CONCLUSIONS:
      A minority of patients undergoing antral PV isolation develops OT VPDs associated
      with a sustained increase in mean heart rate; this effect may result from the
      modulation of adjacent autonomic ganglia.

PMID- 24928486
TI  - Late-occurring left atrial appendage thrombus after ligation using LARIAT.

PMID- 24928487
TI  - Implantable cardioverter-defibrillators in patients with arrhythmogenic right
      ventricular cardiomyopathy: the course of electronic parameters, clinical
      features, and complications during long-term follow-up.
AB  - PURPOSE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive
      cardiomyopathy characterized by myocardial atrophy and fibro-fatty replacement of
      the right ventricle (RV) and ventricular tachyarrhythmias in young patients. Our
      aim was to evaluate clinical course and electronic parameters in patients with
      implantable cardioverter-defibrillator (ICD) and ARVC, during long-term follow
      up. METHODS AND RESULTS: We report on 12 patients with ARVC (mean age 40 +/- 13
      years) who were treated with ICD implantation in our center. Although several RV
      sites were tested for proper lead positions, the amplitude of R-wave at
      implantation was quite low (7.4 +/- 3.0 mV). After a mean follow-up of 91 +/- 28
      months, R-wave amplitude significantly decreased to a mean value of 5.4 +/- 2.5
      mV (p=0.03). We also found a noticeable, nearly significant increase in pacing
      threshold (p=0.052) and a moderate increase in defibrillation impedance (p=0.07).
      Six patients (46 %) experienced at least one appropriate ICD therapy; three
      patients (23 %) experienced inappropriate ICD shocks secondary to the
      supraventricular tachycardia, T-wave oversensing, and electromagnetic
      interference. CONCLUSIONS: ICD in patients with ARVC has been demonstrated to be
      feasible and safe. In our case series, we found low R-wave amplitudes at
      implantation and a significant R-wave decrease during follow-up; a considerable
      and nearly significant increase in pacing threshold was also observed. These
      findings may be related to the progressive fibro-fatty replacement of RV
      myocardium. Multiple sites should be tested in the right ventricle if sensing or
      pacing values are not optimal, and all the electronic parameters should be
      carefully monitored throughout the entire follow-up.

PMID- 24928488
TI  - One size does not fit all: the influence of age at surgery on outcomes following
      Norwood operation.
AB  - BACKGROUND: Given our large catchment area that often results in later
      presentation age, we sought to understand our institutional outcomes for the
      Norwood operation in the context of published data. Specifically, we studied
      whether operative and late death post-Norwood are dependent on age at operation.
      METHODS: Retrospective review of 105 consecutive infants undergoing Norwood (2004
      2011) at our institution. Patients were divided into those undergoing Norwood <=
      7 days of age (N = 43; 41%) and those undergoing Norwood > 7 days of age (N = 63;
      59%). Operative mortality (>=30 days), interstage mortality (between Norwood and
      superior bidirectional Glenn), STS-mortality (operative death + in-hospital
      death), and late mortality, occurring any time following hospital discharge were
      compared among groups. Multivariable factors for mortality at each time-point
      were compared using logistic regression models. RESULTS: Underlying diagnosis was
      HLHS in 67 (64%) with the remainder (N = 38; 36%) being other single ventricle
      variants. Median age at surgery was 8 days (range 1-63 days) and mean weight at
      surgery was 3.2 +/- 0.6 kg. Pulmonary blood flow was provided by a right
      ventricle-pulmonary artery conduit in 94% (N = 99). Overall operative survival
      was 92%, with 73% (N = 66) undergoing bidirectional Glenn. Median age was higher
      for operative survivors compared to non-survivors (12 days vs. 5 days; P =
      0.036), with operative mortality higher for infants <=7 days at Norwood compared
      to infants >7 days at Norwood (14% vs. 3%; P = 0.04). After censoring for in
      hospital death, age <= 7 days was also associated with increased risk for late
      death (26% vs. 5%; P = 0.005). CONCLUSIONS: In contrast to other institutional
      series, infants at our center undergoing Norwood operation at an earlier age have
      worse outcomes. Adoption of published practice patterns could lead to different
      local outcomes because of intangible center-specific effects, underscoring the
      principle that results from one institution may not be generalizable to others.
      Targeted center-specific internal review, if possible, should precede externally
      recommended changes in practice.

PMID- 24928489
TI  - On the left anterior negativity (LAN) in electrophysiological studies of
      morphosyntactic agreement: a commentary on "grammatical agreement processing in
      reading: ERP findings and future directions" by Molinaro et al., 2014.

PMID- 24928490
TI  - Chromate alters root system architecture and activates expression of genes
      involved in iron homeostasis and signaling in Arabidopsis thaliana.
AB  - Soil contamination by hexavalent chromium [Cr(VI) or chromate] due to
      anthropogenic activities has become an increasingly important environmental
      problem. To date few studies have been performed to elucidate the signaling
      networks involved on adaptive responses to (CrVI) toxicity in plants. In this
      work, we report that depending upon its concentration, Cr(VI) alters in different
      ways the architecture of the root system in Arabidopsis thaliana seedlings. Low
      concentrations of Cr (20-40 uM) promoted primary root growth, while
      concentrations higher than 60 uM Cr repressed growth and increased formation of
      root hairs, lateral root primordia and adventitious roots. We analyzed global
      gene expression changes in seedlings grown in media supplied with 20 or 140 uM
      Cr. The level of 731 transcripts was significantly modified in response to Cr
      treatment with only five genes common to both Cr concentrations. Interestingly,
      23 genes related to iron (Fe) acquisition were up-regulated including IRT1, YSL2,
      FRO5, BHLH100, BHLH101 and BHLH039 and the master controllers of Fe deficiency
      responses PYE and BTS were specifically activated in pericycle cells. It was also
      found that increasing concentration of Cr in the plant correlated with a decrease
      in Fe content, but increased both acidification of the rhizosphere and activity
      of the ferric chelate reductase. Supply of Fe to Cr-treated Arabidopsis allowed
      primary root to resume growth and alleviated toxicity symptoms, indicating that
      Fe nutrition is a major target of Cr stress in plants. Our results show that low
      Cr levels are beneficial to plants and that toxic Cr concentrations activate a
      low-Fe rescue system. 

PMID- 24928491
TI  - Characterization of five subgroups of the sieve element occlusion gene family in
      Glycine max reveals genes encoding non-forisome P-proteins, forisomes and
      forisome tails.
AB  - P-proteins are structural phloem proteins discussed to be involved in the rapid
      sealing of injured sieve elements. P-proteins are found in all dicotyledonous and
      some monocotyledonous plants, but additional crystalloid P-proteins, known as
      forisomes, have evolved solely in the Fabaceae. Both types are encoded by members
      of the sieve element occlusion (SEO) gene family, which comprises seven
      phylogenetic subgroups. The Fabaceae-specific subgroup 1 contains genes encoding
      forisome subunits in e.g. Medicago truncatula, Vicia faba, Dipteryx panamensis
      and Canavalia gladiata whereas basal subgroup 5 encodes P-proteins in Nicotiana
      tabacum (tobacco) and Arabidopsis thaliana. The function of remaining subgroups
      is still unknown. We chose Glycine max (soybean) as a model to investigate SEO
      proteins representing different subgroups in one species. We isolated native P
      proteins to determine the SEO protein composition and analyzed the expression
      pattern, localization and structure of the G. max SEO proteins representing five
      of the subgroups. We found that subgroup 1 GmSEO genes encode forisome subunits,
      a member of subgroup 5 encodes a non-forisome P-protein and subgroup 2 GmSEO
      genes encode the components of forisome tails, which are present in a restricted
      selection of Fabaceaen species. We therefore present the first molecular
      characterization of a Fabaceae non-forisome P-protein and the first evidence that
      forisome tails are encoded by a phylogenetically-distinct branch of the SEO gene
      family. 

PMID- 24928493
TI  - Osteopontin binds multiple calcium ions with high affinity and independently of
      phosphorylation status.
AB  - Osteopontin (OPN) is an acidic, intrinsically disordered extracellular matrix
      protein with a capacity to modulate biomineralization in vitro and in vivo. The
      role of posttranslational modification of osteopontin has been intensively
      studied. Phosphorylation of OPN has been demonstrated to play a role in
      inhibition of biomineral formation and growth in vitro. Here, we used isothermal
      titration calorimetry (ITC) to investigate the ability of OPN to bind the
      divalent cations Ca(2+) and Mg(2+), both essential components of inorganic
      minerals in vivo. We found, that bovine OPN binds ~10 Ca(2+) ions with an
      apparent affinity ~50-fold tighter than Mg(2+), both regardless of OPN
      phosphorylation, and with affinities significantly stronger than previously
      reported. These results were confirmed using human derived OPN. This implies that
      a majority of the acidic residues within OPN must be engaged in calcium
      interaction under physiological conditions. 

PMID- 24928492
TI  - Imaging and quantifying solute transport across periosteum: implications for
      muscle-bone crosstalk.
AB  - Muscle and bone are known to act as a functional unit and communicate
      biochemically during tissue development and maintenance. Muscle-derived factors
      (myokines) have been found to affect bone functions in vitro. However, the
      transport times of myokines to penetrate into bone, a critical step required for
      local muscle-bone crosstalk, have not been quantified in situ or in vivo. In this
      study, we investigated the permeability of the periosteum, a major barrier to
      muscle-bone crosstalk by tracking and modeling fluorescent tracers that mimic
      myokines under confocal microscopy. Periosteal surface boundaries and tracer
      penetration within the boundaries were imaged in intact murine tibiae using
      reflected light and time-series xz confocal imaging, respectively. Four
      fluorescent tracers including sodium fluorescein (376Da) and dextrans (3kDa,
      10kDa and 40kDa) were chosen because they represented a wide range of molecular
      weights (MW) of myokines. We found that i) murine periosteum was permeable to the
      three smaller tracers while the 40kDa could not penetrate beyond 40% of the outer
      periosteum within 8h, suggesting that periosteum is semi-permeable with a cut-off
      MW of approximately 40kDa, and ii) the characteristic penetration time through
      the periosteum (~60MUm thick) increased with tracer MW and fit well with a
      relationship tcs=-4.43*10(4)-0.57*MWDa-4*10(4)-8.65*10(8)MWDa-4*10(4), from
      which, the characteristic penetration times of various myokines were
      extrapolated. To achieve effective muscle-bone crosstalk, likely signaling
      candidates should have shorter penetration time than their bioactive time, which
      we assumed to be 5 times of the molecule's half-lifetime in the body. Myokines
      such as PGE2, IGF-1, IL-15 and FGF-2 were predicted to satisfy this requirement.
      In summary, a novel imaging approach was developed and used to investigate the
      transport of myokine mimicking-tracers through the periosteum, enabling further
      quantitative studies of muscle-bone communication in physiologically normal and
      pathological conditions. 

PMID- 24928494
TI  - Effects of Activin A on the phenotypic properties of human periodontal ligament
      cells.
AB  - Periodontal ligament (PDL) tissue plays an important role in tooth preservation
      by structurally maintaining the connection between the tooth root and the bone.
      The mechanisms involved in the healing and regeneration of damaged PDL tissue,
      caused by bacterial infection, caries and trauma, have been explored.
      Accumulating evidence suggests that Activin A, a member of the transforming
      growth factor-beta (TGF-beta) superfamily and a dimer of inhibinbetaa,
      contributes to tissue healing through cell proliferation, migration, and
      differentiation of various target cells. In bone, Activin A has been shown to
      exert an inhibitory effect on osteoblast maturation and mineralization. However,
      there have been no reports examining the expression and function of Activin A in
      human PDL cells (HPDLCs). Thus, we aimed to investigate the biological effects of
      Activin A on HPDLCs. Activin A was observed to be localized in HPDLCs and rat PDL
      tissue. When PDL tissue was surgically damaged, Activin A and IL-1beta expression
      increased and the two proteins were shown to be co-localized around the lesion.
      HPDLCs treated with IL-1beta or TNF-alpha also up-regulated the expression of the
      gene encoding inhibinbetaa. Activin A promoted chemotaxis, migration and
      proliferation of HPDLCs, and caused an increase in fibroblastic differentiation
      of these cells while down-regulating their osteoblastic differentiation. These
      osteoblastic inhibitory effects of Activin A, however, were only noted during the
      early phase of HPDLC osteoblastic differentiation, with later exposures having no
      effect on differentiation. Collectively, our results suggest that Activin A could
      be used as a therapeutic agent for healing and regenerating PDL tissue in
      response to disease, trauma or surgical reconstruction. 

PMID- 24928495
TI  - Quantitative relationships between microdamage and cancellous bone strength and
      stiffness.
AB  - Microscopic tissue damage (microdamage) is an aspect of bone quality associated
      with impaired bone mechanical performance. While it is clear that bone tissue
      submitted to more severe loading has greater amounts of microdamage (as measured
      through staining), how microdamage influences future mechanical performance of
      the bone has not been well studied, yet is necessary for understanding the
      mechanical consequences of the presence of microdamage. Here we determine how
      stained microdamage generated by a single compressive overload affects subsequent
      biomechanical performance of cancellous bone. Human vertebral cancellous bone
      specimens (n=47) from 23 donors (14 males, 9 females, 64-92years of age) were
      submitted to a compressive overload, stained for microdamage, then reloaded in
      compression to determine the relationship between the amount of microdamage
      caused by the initial load and reductions in mechanical performance during the
      reload. Damage volume fraction (DV/BV) caused by the initial overload was related
      to reductions in Young's modulus, yield strength, ultimate strength, and yield
      strain upon reloading (p<0.05, R(2)=0.18-0.34). The regression models suggest
      that, on average, relatively small amounts of microdamage are associated with
      large reductions in reload mechanical properties: a 1.50% DV/BV caused by a
      compressive overload was associated with an average reduction in Young's modulus
      of 41.0+/-3.2% (mean+/-SE), an average reduction in yield strength of 63.1+/-4.5%
      and an average reduction in ultimate strength of 52.7+/-4.0%. Specimens loaded
      beyond 1.2% (1.2-4.0% apparent strain) demonstrated a single relationship between
      reload mechanical properties (Young's modulus, yield strength, and ultimate
      strength) and bone volume fraction despite a large range in amounts of
      microdamage. Hence, estimates of future mechanical performance of cancellous bone
      can be achieved using the bone volume fraction and whether or not a specimen was
      previously loaded beyond ultimate strain. The empirical relationships provided in
      this study make it possible to estimate the degree of impaired mechanical
      performance resulting from an observed amount of stained microdamage. 

PMID- 24928497
TI  - Increased fracture callus mineralization and strength in cathepsin K knockout
      mice.
AB  - Cathepsin K (CatK) is a cysteine protease, expressed predominantly in osteoclasts
      (OC) which degrades demineralized bone matrix. Novel selective inhibitors of CatK
      are currently being developed for the treatment of postmenopausal osteoporosis.
      Pharmacological inhibition of CatK reduces OC resorption activity while
      preserving bone formation in preclinical models. Disruption of the CatK gene in
      mice also results in high bone mass due to impaired bone resorption and elevated
      formation. Here, we assessed mid-shaft femoral fracture healing in 8-10week old
      CatK knock-out (KO) versus wild type (WT) mice. Fracture healing and callus
      formation were determined in vivo weekly via X-ray, and ex vivo at days 14, 18,
      28 and 42 post-fracture by radiographic scoring, micro-computed tomography
      (MUCT), histomorphometry and terminal mechanical four point bend strength
      testing. Radiological evaluation indicated accelerated bone healing and
      remodeling for CatK KO animals based on increased total radiographic scores that
      included callus opacity and bridging at days 28 and 42 post-fracture. Micro-CT
      based total callus volume was similar in CatK KO and WT mice at day 14. Callus
      size in CatK KO mice was 25% smaller than that in WT mice at day 18,
      statistically significant by day 28 and exhibited significantly higher
      mineralized tissue volume and volumetric BMD as compared to WT by day 18 onward.
      Osteoclast surface and osteoid surface trended higher in CatK KO calluses at all
      time-points and osteoblast number was also significantly increased at day 28.
      Increased CatK KO callus mineral density was reflected in significant increases
      in peak load and stiffness over WT at day 42 post-fracture. Regression analysis
      indicated a positive correlation (r=0.8671; p<0.001) between callus BMC and peak
      load indicating normal mineral properties in CatK KO calluses. Taken together,
      gene deletion of cathepsin K in mice accelerated callus size resolution,
      significantly increased callus mineralized mass, and improved mechanical strength
      as compared to wild type mice. 

PMID- 24928496
TI  - Reduced diaphyseal strength associated with high intracortical vascular porosity
      within long bones of children with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The
      mechanisms behind this fragility are not well understood. In addition to
      characteristic bone mass deficiencies, research suggests that bone material
      properties are compromised in individuals with this disorder. However, little
      data exists regarding bone properties beyond the microstructural scale in
      individuals with this disorder. Specimens were obtained from long bone diaphyses
      of nine children with osteogenesis imperfecta during routine osteotomy
      procedures. Small rectangular beams, oriented longitudinally and transversely to
      the diaphyseal axis, were machined from these specimens and elastic modulus,
      yield strength, and maximum strength were measured in three-point bending.
      Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density,
      and volumetric tissue mineral density were determined by synchrotron micro
      computed tomography, and relationships among these mechanical properties and
      structural parameters were explored. Modulus and strength were on average 64-68%
      lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model).
      Vascular porosity ranged between 3 and 42% of total bone volume. Longitudinal
      properties were associated negatively with porosity (P<=0.006, linear
      regressions). Mechanical properties, however, were not associated with osteocyte
      lacuna density or volumetric tissue mineral density (P>=0.167). Bone properties
      and structural parameters were not associated significantly with donor age
      (P>=0.225, linear mixed models). This study presents novel data regarding bone
      material strength in children with osteogenesis imperfecta. Results confirm that
      these properties are anisotropic. Elevated vascular porosity was observed in most
      specimens, and this parameter was associated with reduced bone material strength.
      These results offer insight toward understanding bone fragility and the role of
      intracortical porosity on the strength of bone tissue in children with
      osteogenesis imperfecta. 

PMID- 24928498
TI  - Magnetic resonance imaging assessed cortical porosity is highly correlated with
      MUCT porosity.
AB  - Cortical bone is typically regarded as "MR invisible" with conventional clinical
      magnetic resonance imaging (MRI) pulse sequences. However, recent studies have
      demonstrated that free water in the microscopic pores of cortical bone has a
      short T2* but a relatively long T2, and may be detectable with conventional
      clinical spin echo (SE) or fast spin echo (FSE) sequences. In this study we
      describe the use of a conventional two-dimensional (2D) FSE sequence to assess
      cortical bone microstructure and measure cortical porosity using a clinical 3T
      scanner. Twelve cadaveric human cortical bone samples were studied with MRI and
      microcomputed tomography (MUCT) (downsampled to the same spatial resolution).
      Preliminary results show that FSE-determined porosity is highly correlated
      (R(2)=0.83; P<0.0001) with MUCT porosity. Bland-Altman analysis suggested a good
      agreement between FSE and MUCT with tight limit of agreement at around 3%. There
      is also a small bias of -2% for the FSE data, which suggested that the FSE
      approach slightly underestimated MUCT porosity. The results demonstrate that
      cortical porosity can be directly assessed using conventional clinical FSE
      sequences. The clinical feasibility of this approach was also demonstrated on six
      healthy volunteers using 2D FSE sequences as well as 2D ultrashort echo time
      (UTE) sequences with a minimal echo time (TE) of 8MUs, which provide high
      contrast imaging of cortical bone in vivo. 

PMID- 24928500
TI  - Emerging from the PAC: studying zebrafish lymphatic development.
AB  - Recently the zebrafish has emerged as a promising vertebrate model of lymphatic
      vasculature development. The establishment of numerous transgenic lines that
      label the lymphatic endothelium in the zebrafish has allowed the fine examination
      of the developmental timing and the anatomy of their lymphatic vasculature.
      Although many questions remain, studying lymphatic development in the zebrafish
      has resulted in the identification and characterization of novel and established
      mediators of lymphatic development and lymphangiogenesis. Here, we review the
      main stages involved in the development of the lymphatic vasculature in the
      zebrafish from its origins in the embryonic veins to the formation of the primary
      lymphatic vessels and highlight some of the key molecules necessary for these
      stages. 

PMID- 24928499
TI  - Molecular and cellular mechanisms of lymphatic vascular maturation.
AB  - Lymphatic vasculature is necessary for maintaining fluid homeostasis in
      vertebrates. During embryogenesis lymphatic endothelial cells originate from the
      veins as a homogeneous population. These cells undergo a series of changes at the
      morphological and molecular levels to become mature lymphatic vasculature that
      consists of lymphatic capillaries, collecting lymphatic vessels and valves. In
      this article we summarize our current knowledge about these steps and highlight
      some black boxes that require further clarification. 

PMID- 24928501
TI  - Transurethral excision of prolapsed ureterocele.
AB  - INTRODUCTION: A ureterocele is a cystic dilation of the terminal ureter. The
      incidence ranges from 1/500 to 1/1,200. Ureteroceles are more commonly diagnosed
      in women; 10% are bilateral, and 80% are associated with the upper pole of a
      duplicated system. A prolapsed ureterocele is one that extends to or beyond the
      urethral meatus, and the incidence is unknown. Managing prolapsed ureterocele in
      adult women is not well described in the literature. METHODS: The aim of this
      video is to demonstrate the technique of transurethral excision of a prolapsed
      ureterocele associated with a normal kidney in an adult woman, which eliminates
      the ureterocele while avoiding the morbidity of open surgical excision. RESULTS:
      The patient initially underwent transurethral incision of the ureterocele, after
      which her obstructive symptoms improved. However, she still complained of a mass
      protruding from her urethra. The patient subsequently underwent transurethral
      excision of the ureterocele. On the 18-month follow-up, she was voiding without
      difficulty and had no residual urethral mass. She is being followed clinically,
      and upper urinary tract imaging will be performed to rule out hydronephrosis or
      vesicoureteral reflux, as indicated. Pathology revealed urothelial mucosa.
      CONCLUSION: Transurethral incision of a prolapsed ureterocele can be attempted as
      first-line treatment due to the low morbidity of the procedure. If the patient
      still has lower urinary tract symptoms, transurethral excision can successfully
      treat a large prolapsed ureterocele.

PMID- 24928502
TI  - Mobility impairments and pelvic health disorders in women: the need for
      innovative treatment and research.

PMID- 24928503
TI  - Treatment-seeking behaviour and social status of women with pelvic organ
      prolapse, 4th-degree obstetric tears, and obstetric fistula in western Uganda.
AB  - INTRODUCTION AND HYPOTHESIS: This study looks at a trilogy of women's health
      issues including severe pelvic organ prolapse, unrepaired 4th degree obstetric
      tears and obstetric fistula, all of which can cause significant suffering in the
      lives of women and their families. METHODS: Women undergoing surgery for severe
      pelvic organ prolapse, unrepaired 4th degree obstetric tears and obstetric
      fistulae, were interviewed to assess their perceptions of what caused their
      condition, subsequent impact on their social situation and sexual activity, and
      whether they had sought treatment previously. RESULTS: One hundred fifty women
      participated in the survey, including 69 undergoing surgery for genito-urinary
      fistula, 25 with faecal incontinence only (including 24 women with unrepaired 4th
      degree obstetric tears and 1 woman with an isolated rectovaginal fistula), and 56
      women with severe pelvic organ prolapse. All groups of women were exposed to
      abandonment by their families with 42 % of women with genito-urinary fistula, 21
      % with unrepaired 4th degree obstetric tear, and 25 % of women with severe pelvic
      organ prolapse rejected by their husbands. Most of the women had actively sought
      treatment for their condition with no success due to unavailability of treatment
      or misinformation. CONCLUSIONS: This study confirms the social stigma associated
      with obstetric fistula, however also highlights the social stigma faced by women
      suffering with severe pelvic organ prolapse and unrepaired 4th degree obstetric
      tears in western Uganda. There is an urgent need for education and training in
      obstetric management and pelvic organ prolapse management in such areas of
      limited resources.

PMID- 24928504
TI  - Norovirus translation requires an interaction between the C Terminus of the
      genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.
AB  - Viruses have evolved a variety of mechanisms to usurp the host cell translation
      machinery to enable translation of the viral genome in the presence of high
      levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man,
      have evolved a mechanism that relies on the interaction of translation initiation
      factors with the virus-encoded VPg protein covalently linked to the 5' end of the
      viral RNA. To further characterize this novel mechanism of translation
      initiation, we have used proteomics to identify the components of the norovirus
      translation initiation factor complex. This approach revealed that VPg binds
      directly to the eIF4F complex, with a high affinity interaction occurring between
      VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is
      important for the VPg-eIF4G interaction; viruses with mutations that alter or
      disrupt this interaction are debilitated or non-viable. Our results shed new
      light on the unusual mechanisms of protein-directed translation initiation. 

PMID- 24928505
TI  - Mechanistic insight into the enzymatic reduction of truncated hemoglobin N of
      Mycobacterium tuberculosis: role of the CD loop and pre-A motif in electron
      cycling.
AB  - Many pathogenic microorganisms have evolved hemoglobin-mediated nitric oxide (NO)
      detoxification mechanisms, where a globin domain in conjunction with a partner
      reductase catalyzes the conversion of toxic NO to innocuous nitrate. The
      truncated hemoglobin HbN of Mycobacterium tuberculosis displays a potent NO
      dioxygenase activity despite lacking a reductase domain. The mechanism by which
      HbN recycles itself during NO dioxygenation and the reductase that participates
      in this process are currently unknown. This study demonstrates that the NADH
      ferredoxin/flavodoxin system is a fairly efficient partner for electron transfer
      to HbN with an observed reduction rate of 6.2 MUM/min(-1), which is nearly 3- and
      5-fold faster than reported for Vitreoscilla hemoglobin and myoglobin,
      respectively. Structural docking of the HbN with Escherichia coli NADH-flavodoxin
      reductase (FdR) together with site-directed mutagenesis revealed that the CD loop
      of the HbN forms contacts with the reductase, and that Gly(48) may have a vital
      role. The donor to acceptor electron coupling parameters calculated using the
      semiempirical pathway method amounts to an average of about 6.4 10(-5) eV, which
      is lower than the value obtained for E. coli flavoHb (8.0 10(-4) eV), but still
      supports the feasibility of an efficient electron transfer. The deletion of Pre-A
      abrogated the heme iron reduction by FdR in the HbN, thus signifying its
      involvement during intermolecular interactions of the HbN and FdR. The present
      study, thus, unravels a novel role of the CD loop and Pre-A motif in assisting
      the interactions of the HbN with the reductase and the electron cycling, which
      may be vital for its NO-scavenging function.

PMID- 24928506
TI  - Sphingosine, a modulator of human translesion DNA polymerase activity.
AB  - Translesion (TLS) DNA polymerases are specialized, error-prone enzymes that
      synthesize DNA across bulky, replication-stalling DNA adducts. In so doing, they
      facilitate the progression of DNA synthesis and promote cell proliferation. To
      potentiate the effect of cancer chemotherapeutic regimens, we sought to identify
      inhibitors of TLS DNA polymerases. We screened five libraries of ~ 3000 small
      molecules, including one comprising ~ 600 nucleoside analogs, for their effect on
      primer extension activity of DNA polymerase eta (Pol eta). We serendipitously
      identified sphingosine, a lipid-signaling molecule that robustly stimulates the
      activity of Pol eta by ~ 100-fold at low micromolar concentrations but inhibits
      it at higher concentrations. This effect is specific to the Y-family DNA
      polymerases, Pols eta, kappa, and iota. The addition of a single phosphate group
      on sphingosine completely abrogates this effect. Likewise, the inclusion of other
      sphingolipids, including ceramide and sphingomyelin to extension reactions does
      not elicit this response. Sphingosine increases the rate of correct and incorrect
      nucleotide incorporation while having no effect on polymerase processivity.
      Endogenous Pol eta activity is modulated similarly as the recombinant enzyme.
      Importantly, sphingosine-treated cells exhibit increased lesion bypass activity,
      and sphingosine tethered to membrane lipids mimics the effects of free
      sphingosine. Our studies have uncovered sphingosine as a modulator of TLS DNA
      polymerase activity; this property of sphingosine may be associated with its
      known role as a signaling molecule in regulating cell proliferation in response
      to cellular stress.

PMID- 24928507
TI  - Ror2 receptor mediates Wnt11 ligand signaling and affects convergence and
      extension movements in zebrafish.
AB  - The receptor-tyrosine kinase Ror2 acts as an alternative receptor or co-receptor
      for Wnt5a and mediates Wnt5a-induced convergent extension movements during
      embryogenesis in mice and Xenopus as well as the polarity and migration of
      several cell types during development. However, little is known about whether
      Ror2 function is conserved in other vertebrates or is involved in other non
      canonical Wnt ligands in vivo. In this study we demonstrated that overexpression
      of dominant-negative ror2 (ror2-TM) mRNA in zebrafish embryos resulted in
      convergence and extension defects and incompletely separated eyes, which is
      consistent with observations from slb/wnt11 mutants or wnt11 knockdown morphants.
      Moreover, the co-injection of ror2-TM mRNA and a wnt11 morpholino or the
      coexpression of ror2 and wnt11 in zebrafish embryos synergetically induced more
      severe convergence and extension defects. Transplantation studies further
      demonstrated that the Ror2 receptor responded to the Wnt11 ligand and regulated
      cell migration and cell morphology during gastrulation. DnRor2 inhibited the
      action of Wnt11, which was revealed by a decreased percentage of Wnt11-induced
      convergence and extension defects. Ror2 physically interacts with Wnt11.
      Theintracellular Tyr-647andSer-863 sites ofRor2are essential for mediating the
      action of Wnt11. Dishevelled and RhoA act downstream of Wnt11-Ror2 to regulate
      convergence and extension movements. Overall, our data suggest an important role
      of Ror2 in mediating Wnt11 signaling and in regulating convergence and extension
      movements in zebrafish.

PMID- 24928508
TI  - Low concentrations of metformin suppress glucose production in hepatocytes
      through AMP-activated protein kinase (AMPK).
AB  - Metformin is a first-line antidiabetic agent taken by 150 million people across
      the world every year, yet its mechanism remains only partially understood and
      controversial. It was proposed that suppression of glucose production in
      hepatocytes by metformin is AMPK-independent; however, unachievably high
      concentrations of metformin were employed in these studies. In the current study,
      we find that metformin, via an AMP-activated protein kinase (AMPK)-dependent
      mechanism, suppresses glucose production and gluconeogenic gene expression in
      primary hepatocytes at concentrations found in the portal vein of animals (60-80
      MUM). Metformin also inhibits gluconeogenic gene expression in the liver of mice
      administered orally with metformin. Furthermore, the cAMP-PKA pathway negatively
      regulates AMPK activity through phosphorylation at Ser-485/497 on the alpha
      subunit, which in turn reduces net phosphorylation at Thr-172. Because diabetic
      patients often have hyperglucagonemia, AMPKalpha phosphorylation at Ser-485/497
      is a therapeutic target to improve metformin efficacy.

PMID- 24928509
TI  - An adenosine receptor-Kruppel-like factor 4 protein axis inhibits adipogenesis.
AB  - Adipogenesis represents a key process in adipose tissue development and
      remodeling, including during obesity. Exploring the regulation of adipogenesis by
      extracellular ligands is fundamental to our understanding of this process.
      Adenosine, an extracellular nucleoside signaling molecule found in adipose tissue
      depots, acts on adenosine receptors. Here we report that, among these receptors,
      the A2b adenosine receptor (A2bAR) is highly expressed in adipocyte progenitors.
      Activation of the A2bAR potently inhibits differentiation of mouse stromal
      vascular cells into adipocytes, whereas A2bAR knockdown stimulates adipogenesis.
      The A2bAR inhibits differentiation through a novel signaling cascade involving
      sustained expression of Kruppel-like factor 4 (KLF4), a regulator of stem cell
      maintenance. Knockdown of KLF4 ablates the ability of the A2bAR to inhibit
      differentiation. A2bAR activation also inhibits adipogenesis in a human primary
      preadipocyte culture system. We analyzed the A2bARKLF4 axis in adipose tissue of
      obese subjects and, intriguingly, found a strong correlation between A2bAR and
      KLF4 expression in both subcutaneous and visceral human fat. Hence, our study
      implicates the A2bAR as a regulator of adipocyte differentiation and the A2bAR
      KLF4 axis as a potentially significant modulator of adipose biology.

PMID- 24928510
TI  - Glucose activates TORC2-Gad8 protein via positive regulation of the cAMP/cAMP
      dependent protein kinase A (PKA) pathway and negative regulation of the Pmk1
      protein-mitogen-activated protein kinase pathway.
AB  - The target of rapamycin (TOR) kinase belongs to the highly conserved eukaryotic
      family of phosphatidylinositol 3-kinase-related kinases. TOR proteins are found
      at the core of two evolutionary conserved complexes, known as TORC1 and TORC2. In
      fission yeast, TORC2 is dispensable for proliferation under optimal growth
      conditions but is required for starvation and stress responses. TORC2 has been
      implicated in a wide variety of functions; however, the signals that regulate
      TORC2 activity have so far remained obscure. TORC2 has one known direct
      substrate, the AGC kinase Gad8, which is related to AKT in human cells. Gad8 is
      phosphorylated by TORC2 at Ser-546 (equivalent to AKT Ser-473), leading to its
      activation. Here, we show that glucose is necessary and sufficient to induce Gad8
      Ser-546 phosphorylation in vivo and Gad8 kinase activity in vitro. The glucose
      signal that activates TORC2-Gad8 is mediated via the cAMP/PKA pathway, a major
      glucose-sensing pathway. By contrast, Pmk1, similar to human extracellular signal
      regulated kinases and a major stress-induced mitogen activated protein kinase
      (MAPK) in fission yeast, inhibits TORC2-dependent Gad8 phosphorylation and
      activation. Inhibition of TORC2-Gad8 also occurs in response to ionic or osmotic
      stress, in a manner dependent on the cAMP/PKA and Pmk1-MAPK signaling pathways.
      Our findings highlight the significance of glucose availability in regulation of
      TORC2-Gad8 and indicate a novel link between the cAMP/PKA, Pmk1/MAPK, and TORC2
      Gad8 signaling. 

PMID- 24928511
TI  - Epidermal growth factor receptor (EGFR) signaling regulates global metabolic
      pathways in EGFR-mutated lung adenocarcinoma.
AB  - Genetic mutations in tumor cells cause several unique metabolic phenotypes that
      are critical for cancer cell proliferation. Mutations in the tyrosine kinase
      epidermal growth factor receptor (EGFR) induce oncogenic addiction in lung
      adenocarcinoma (LAD). However, the linkage between oncogenic mutated EGFR and
      cancer cell metabolism has not yet been clearly elucidated. Here we show that
      EGFR signaling plays an important role in aerobic glycolysis in EGFR-mutated LAD
      cells. EGFR-tyrosine kinase inhibitors (TKIs) decreased lactate production,
      glucose consumption, and the glucose-induced extracellular acidification rate
      (ECAR), indicating that EGFR signaling maintained aerobic glycolysis in LAD
      cells. Metabolomic analysis revealed that metabolites in the glycolysis, pentose
      phosphate pathway (PPP), pyrimidine biosynthesis, and redox metabolism were
      significantly decreased after treatment of LAD cells with EGFRTKI. On a molecular
      basis, the glucose transport carried out by glucose transporter 3 (GLUT3) was
      downregulated in TKI-sensitive LAD cells. Moreover, EGFR signaling activated
      carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
      (CAD), which catalyzes the first step in de novo pyrimidine synthesis. We
      conclude that EGFR signaling regulates the global metabolic pathway in EGFR
      mutated LAD cells. Our data provide evidence that may link therapeutic response
      to the regulation of metabolism, which is an attractive target for the
      development of more effective targeted therapies to treat patients with EGFR
      mutated LAD.

PMID- 24928512
TI  - High mobility group box-1 (HMGB1) participates in the pathogenesis of alcoholic
      liver disease (ALD).
AB  - Growing clinical and experimental evidence suggests that sterile inflammation
      contributes to alcoholic liver disease (ALD). High mobility group box-1 (HMGB1)
      is highly induced during liver injury; however, a link between this alarmin and
      ALD has not been established. Thus, the aim of this work was to determine whether
      HMGB1 contributes to the pathogenesis of ALD. Liver biopsies from patients with
      ALD showed a robust increase in HMGB1 expression and translocation, which
      correlated with disease stage, compared with healthy explants. Similar findings
      were observed in chronic ethanol-fed wild-type (WT) mice. Using primary cell
      culture, we validated the ability of hepatocytes from ethanol-fed mice to secrete
      a large amount of HMGB1. Secretion was time- and dose-dependent and responsive to
      prooxidants and antioxidants. Selective ablation of Hmgb1 in hepatocytes
      protected mice from alcohol-induced liver injury due to increased carnitine
      palmitoyltransferase-1, phosphorylated 5'AMP-activated protein kinase-alpha, and
      phosphorylated peroxisome proliferator-activated receptor-alpha expression along
      with elevated LDL plus VLDL export. Native and post-translationally modified
      HMGB1 were detected in humans and mice with ALD. In liver and serum from control
      mice and in serum from healthy volunteers, the lysine residues within the
      peptides containing nuclear localization signals (NLSs) 1 and 2 were non
      acetylated, and all cysteine residues were reduced. However, in livers from
      ethanol-fed mice, in addition to all thiol/non-acetylated isoforms of HMGB1, we
      observed acetylated NLS1 and NLS2, a unique phosphorylation site in serine 35,
      and an increase in oxidation of HMGB1 to the disulfide isoform. In serum from
      ethanol-fed mice and from patients with ALD, there was disulfide-bonded
      hyperacetylated HMGB1, disulfide-bonded non-acetylated HMGB1, and HMGB1
      phosphorylated in serine 35. Hepatocytes appeared to be a major source of these
      HMGB1 isoforms. Thus, hepatocyte HMGB1 participates in the pathogenesis of ALD
      and undergoes post-translational modifications (PTMs) that could condition its
      toxic effects. 

PMID- 24928513
TI  - Uric acid and thiocyanate as competing substrates of lactoperoxidase.
AB  - The physiological function of urate is poorly understood. It may act as a danger
      signal, an antioxidant, or a substrate for heme peroxidases. Whether it reacts
      sufficiently rapidly with lactoperoxidase (LPO) to act as a physiological
      substrate remains unknown. LPO is a mammalian peroxidase that plays a key role in
      the innate immune defense by oxidizing thiocyanate to the bactericidal and
      fungicidal agent hypothiocyanite. We now demonstrate that urate is a good
      substrate for bovine LPO. Urate was oxidized by LPO to produce the electrophilic
      intermediates dehydrourate and 5-hydroxyisourate, which decayed to allantoin. In
      the presence of superoxide, high yields of hydroperoxides were formed by LPO and
      urate. Using stopped-flow spectroscopy, we determined rate constants for the
      reaction of urate with compound I (k1 = 1.1 * 10(7) M(-1) s(-1)) and compound II
      (k2 = 8.5 * 10(3) M(-1) s(-1)). During urate oxidation, LPO was diverted from its
      peroxidase cycle because hydrogen peroxide reacted with compound II to give
      compound III. At physiologically relevant concentrations, urate competed
      effectively with thiocyanate, the main substrate of LPO for oxidation, and
      inhibited production of hypothiocyanite. Similarly, hypothiocyanite-dependent
      killing of Pseudomonas aeruginosa was inhibited by urate. Allantoin was present
      in human saliva and associated with the concentration of LPO. When hydrogen
      peroxide was added to saliva, oxidation of urate was dependent on its
      concentration and peroxidase activity. Our findings establish urate as a likely
      physiological substrate for LPO that will influence host defense and give rise to
      reactive electrophilic metabolites.

PMID- 24928514
TI  - A novel interaction between the SH2 domain of signaling adaptor protein Nck-1 and
      the upstream regulator of the Rho family GTPase Rac1 engulfment and cell motility
      1 (ELMO1) promotes Rac1 activation and cell motility.
AB  - Nck family proteins function as adaptors to couple tyrosine phosphorylation
      signals to actin cytoskeleton reorganization. Several lines of evidence indicate
      that Nck family proteins involve in regulating the activity of Rho family
      GTPases. In the present study, we characterized a novel interaction between Nck-1
      with engulfment and cell motility 1 (ELMO1). GST pull-down and co
      immunoprecipitation assay demonstrated that the Nck-1-ELMO1 interaction is
      mediated by the SH2 domain of Nck-1 and the phosphotyrosine residues at position
      18, 216, 395, and 511 of ELMO1. A R308K mutant of Nck-1 (in which the SH2 domain
      was inactive), or a 4YF mutant of ELMO1 lacking these four phosphotyrosine
      residues, diminished Nck-1-ELMO1 interaction. Conversely, tyrosine phosphatase
      inhibitor treatment and overexpression of Src family kinase Hck significantly
      enhanced Nck-1-ELMO1 interaction. Moreover, wild type Nck-1, but not R308K
      mutant, significantly augmented the interaction between ELMO1 and constitutively
      active RhoG (RhoG(V12A)), thus promoted Rac1 activation and cell motility. Taken
      together, the present study characterized a novel Nck-1-ELMO1 interaction and
      defined a new role for Nck-1 in regulating Rac1 activity. 

PMID- 24928515
TI  - Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse
      cortical neurons.
AB  - Sphingosine kinase 2 (SPK2) and autophagy are both involved in brain
      preconditioning, but whether preconditioning-induced SPK2 up-regulation and
      autophagy activation are linked mechanistically remains to be elucidated. In this
      study, we used in vitro and in vivo models to explore the role of SPK2-mediated
      autophagy in isoflurane and hypoxic preconditioning. In primary mouse cortical
      neurons, both isoflurane and hypoxic preconditioning induced autophagy.
      Isoflurane and hypoxic preconditioning protected against subsequent oxygen
      glucose deprivation or glutamate injury, whereas pretreatment with autophagy
      inhibitors (3-methyladenine or KU55933) abolished preconditioning-induced
      tolerance. Pretreatment with SPK2 inhibitors (ABC294640 and SKI-II) or SPK2
      knockdown prevented preconditioning-induced autophagy. Isoflurane also induced
      autophagy in mouse in vivo as shown by Western blots for LC3 and p62, LC3
      immunostaining, and electron microscopy. Isoflurane-induced autophagy in mice
      lacking the SPK1 isoform (SPK1(-/-)), but not in SPK2(-/-)mice. Sphingosine 1
      phosphate and the sphingosine 1-phosphate receptor agonist FTY720 did not protect
      against oxygen glucose deprivation in cultured neurons and did not alter the
      expression of LC3 and p62, suggesting that SPK2-mediated autophagy and
      protections are not S1P-dependent. Beclin 1 knockdown abolished preconditioning
      induced autophagy, and SPK2 inhibitors abolished isoflurane-induced disruption of
      the Beclin 1/Bcl-2 association. These results strongly indicate that autophagy is
      involved in isoflurane preconditioning both in vivo and in vitro and that SPK2
      contributes to preconditioning-induced autophagy, possibly by disrupting the
      Beclin 1/Bcl-2 interaction.

PMID- 24928516
TI  - Real-time measurements of amino acid and protein hydroperoxides using coumarin
      boronic acid.
AB  - Hydroperoxides of amino acid and amino acid residues (tyrosine, cysteine,
      tryptophan, and histidine) in proteins are formed during oxidative modification
      induced by reactive oxygen species. Amino acid hydroperoxides are unstable
      intermediates that can further propagate oxidative damage in proteins. The
      existing assays (oxidation of ferrous cation and iodometric assays) cannot be
      used in real-time measurements. In this study, we show that the profluorescent
      coumarin boronic acid (CBA) probe reacts with amino acid and protein
      hydroperoxides to form the corresponding fluorescent product, 7-hydroxycoumarin.
      7-Hydroxycoumarin formation was catalase-independent. Based on this observation,
      we have developed a fluorometric, real-time assay that is adapted to a multiwell
      plate format. This is the first report showing real-time monitoring of amino acid
      and protein hydroperoxides using the CBA-based assay. This approach was used to
      detect protein hydroperoxides in cell lysates obtained from macrophages exposed
      to visible light and photosensitizer (rose bengal). We also measured the rate
      constants for the reaction between amino acid hydroperoxides (tyrosyl,
      tryptophan, and histidine hydroperoxides) and CBA, and these values (7-23 M(-1)
      s(-1)) were significantly higher than that measured for H2O2 (1.5 M(-1) s(-1)).
      Using the CBA-based competition kinetics approach, the rate constants for amino
      acid hydroperoxides with ebselen, a glutathione peroxidase mimic, were also
      determined, and the values were within the range of 1.1-1.5 * 10(3) M(-1) s(-1).
      Both ebselen and boronates may be used as small molecule scavengers of amino acid
      and protein hydroperoxides. Here we also show formation of tryptophan
      hydroperoxide from tryptophan exposed to co-generated fluxes of nitric oxide and
      superoxide. This observation reveals a new mechanism for amino acid and protein
      hydroperoxide formation in biological systems.

PMID- 24928517
TI  - Biochemical and spatial coincidence in the provisional Ser/Thr protein kinase
      interaction network of Mycobacterium tuberculosis.
AB  - Many Gram-positive bacteria coordinate cellular processes by signaling through
      Ser/Thr protein kinases (STPKs), but the architecture of these phosphosignaling
      cascades is unknown. To investigate the network structure of a prokaryotic STPK
      system, we comprehensively explored the pattern of signal transduction in the
      Mycobacterium tuberculosis Ser/Thr kinome. Autophosphorylation is the dominant
      mode of STPK activation, but the 11 M. tuberculosis STPKs also show a specific
      pattern of efficient cross-phosphorylation in vitro. The biochemical specificity
      intrinsic to each kinase domain was used to map the provisional signaling
      network, revealing a three-layer architecture that includes master regulators,
      signal transducers, and terminal substrates. Fluorescence microscopy revealed
      that the STPKs are specifically localized in the cell. Master STPKs are
      concentrated at the same subcellular sites as their substrates, providing
      additional support for the biochemically defined network. Together, these studies
      imply a branched functional architecture of the M. tuberculosis Ser/Thr kinome
      that could enable horizontal signal spreading. This systems-level approach
      provides a biochemical and spatial framework for understanding Ser/Thr phospho
      signaling in M. tuberculosis, which differs fundamentally from previously defined
      linear histidine kinase cascades.

PMID- 24928518
TI  - [Percutaneous titanium implants for bone conduction hearing aids: experience with
      283 cases].
AB  - BACKGROUND: By virtue of direct bone conduction, percutaneous bone-anchored
      hearing implants offer a high level of wearing comfort, as well as audiologically
      superior signal transmission due to less dampening. Over the years, titanium
      implants have been optimized and the surgical technique developed into a
      minimally invasive intervention without soft tissue reduction. This study aims to
      investigate the success rates of the various percutaneous implant systems.
      MATERIALS AND METHODS: This retrospective study includes 191 patients who
      received a total of 283 percutaneous titanium implants for bone conduction
      hearing systems during the period from 01.01.1989 until 31.12.2013. Patient age
      ranged from 2 to 81 years (mean 36 years). The mean follow-up duration was 5.2
      years. RESULTS: The overall osseointegration success rate was 92.6% and ranged
      from 90.5 to 100% for the various implant systems (p = 0.6). For children and
      adolescents, the success rate was 86.8%, compared to 95.2% in adults (p = 0.023).
      Classical soft tissue reduction was received by 185 patients, mainly via the
      dermatome technique. The linear incision technique was used in 3.8% of cases and
      the technique without soft tissue reduction in 3.7% of cases. Revision surgery
      for soft tissue problems was performed in 4.2% of cases. CONCLUSION: Success
      rates in adults were significantly higher than those in children and adolescents.
      Although success rates improved with the development of new systems, this did not
      reach statistical significance. Minimally invasive surgery without soft tissue
      reduction is considered state of the art.

PMID- 24928519
TI  - GSK3-like kinases positively modulate abscisic acid signaling through
      phosphorylating subgroup III SnRK2s in Arabidopsis.
AB  - Arabidopsis glycogen synthase kinase 3 (GSK3)-like kinases have versatile
      functions in plant development and in responding to abiotic stresses. Although
      physiological evidence suggested a potential role of GSK3-like kinases in
      abscisic acid (ABA) signaling, the underlying molecular mechanism was largely
      unknown. Here we identified members of Snf1-related kinase 2s (SnRK2s), SnRK2.2
      and SnRK2.3, that can interact with and be phosphorylated by a GSK3-like kinase,
      brassinosteroid insensitive 2 (BIN2). bin2-3 bil1 bil2, a loss-of-function mutant
      of BIN2 and its two closest homologs, BIN2 like 1 (BIL1) and BIN2 like 2 (BIL2),
      was hyposensitive to ABA in primary root inhibition, ABA-responsive gene
      expression, and phosphorylating ABA Response Element Binding Factor (ABF) 2
      fragment by in-gel kinase assays, whereas bin2-1, a gain-of-function mutation of
      BIN2, was hypersensitive to ABA, suggesting that these GSK3-like kinases function
      as positive regulators in ABA signaling. Furthermore, BIN2 phosphorylated SnRK2.3
      on T180, and SnRK2.3(T180A) had decreased kinase activity in both
      autophosphorylation and phosphorylating ABFs. Bikinin, a GSK3 kinase inhibitor,
      inhibited the SnRK2.3 kinase activity and its T180 phosphorylation in vivo. Our
      genetic analysis further demonstrated that BIN2 regulates ABA signaling
      downstream of the PYRABACTIN RESISTANCE1/PYR1-LIKE/REGULATORY COMPONENTS OF ABA
      RECEPTORS receptors and clade A protein phosphatase 2C but relies on SnRK2.2 and
      SnRK2.3. These findings provide significant insight into the modulation of ABA
      signaling by Arabidopsis GSK3-like kinases. 

PMID- 24928520
TI  - Chem-seq permits identification of genomic targets of drugs against androgen
      receptor regulation selected by functional phenotypic screens.
AB  - Understanding the mechanisms by which compounds discovered using cell-based
      phenotypic screening strategies might exert their effects would be highly
      augmented by new approaches exploring their potential interactions with the
      genome. For example, altered androgen receptor (AR) transcriptional programs,
      including castration resistance and subsequent chromosomal translocations, play
      key roles in prostate cancer pathological progression, making the quest for
      identification of new therapeutic agents and an understanding of their actions a
      continued priority. Here we report an approach that has permitted us to uncover
      the sites and mechanisms of action of a drug, referred to as "SD70," initially
      identified by phenotypic screening for inhibitors of ligand and genotoxic stress
      induced translocations in prostate cancer cells. Based on synthesis of a
      derivatized form of SD70 that permits its application for a ChIP-sequencing-like
      approach, referred to as "Chem-seq," we were next able to efficiently map the
      genome-wide binding locations of this small molecule, revealing that it largely
      colocalized with AR on regulatory enhancers. Based on these observations, we
      performed the appropriate global analyses to ascertain that SD70 inhibits the
      androgen-dependent AR program, and prostate cancer cell growth, acting, at least
      in part, by functionally inhibiting the Jumonji domain-containing demethylase,
      KDM4C. Global location of candidate drugs represents a powerful strategy for new
      drug development by mapping genome-wide location of small molecules, a powerful
      adjunct to contemporary drug development strategies.

PMID- 24928521
TI  - Functional deficiency of NBN, the Nijmegen breakage syndrome protein, in a
      p.R215W mutant breast cancer cell line.
AB  - BACKGROUND: Mutations in NBN, the gene for Nijmegen Breakage Syndrome (NBS), are
      thought to predispose women to developing breast cancer, but a breast cancer cell
      line containing mutations in NBN has not yet been described. The p.R215W missense
      mutation occurs at sub-polymorphic frequencies in several populations. We aimed
      to investigate its functional impact in breast cancer cells from a carrier of
      this NBN mutation. METHODS: Breast cancer cell lines were screened by
      immunoblotting for NBN protein levels, and the NBN coding region was sequenced
      for mutation analysis. Radiosensitivity assays and functional studies were
      performed through immunocytochemistry and immunoblotting, and flow cytometry was
      employed to assess cell cycle progression. Impedance measurements were used to
      study the consequences of PARP1 inhibition. Statistical comparisons between cell
      lines were performed using t-tests. RESULTS: HCC1395 breast cancer cells
      exhibited reduced NBN protein levels. Direct sequencing identified the NBN
      p.R215W mutation in the hemizygous state, in addition to a truncation in BRCA1.
      Mutations in both genes were already present in the heterozygous state in the
      patient's germline. HCC1395 cells were highly radiosensitive, susceptible to
      apoptosis and were deficient in the formation of NBN foci. There was also
      evidence for some impairment in the formation of gammaH2AX, MDC1, and 53BP1 foci
      after irradiation; these foci appeared smaller and irregular compared with repair
      foci in wild-type cells, although ATM signalling was largely unaffected. In line
      with their deficiency in NBN and BRCA1, HCC1395 cells were particularly sensitive
      to PARP1 inhibition. CONCLUSION: Our results indicate that the p.R215W mutation
      in the HCC1395 breast cancer cell line impairs NBN function, making this cell
      line a potentially useful cellular model for studying defective NBN protein
      within a mutant BRCA1 background.

PMID- 24928522
TI  - Small lymphocytic lymphoma presenting as bulky renal incidentaloma.

PMID- 24928523
TI  - Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a
      consolidation therapy after autologous stem cell transplantation for symptomatic
      multiple myeloma in Japanese patients.
AB  - Consolidation therapy for patients with multiple myeloma (MM) has been widely
      adopted to improve treatment response following autologous stem cell
      transplantation. In this study, we retrospectively analyzed the safety and
      efficacy of combination regimen of bortezomib, thalidomide, and dexamethasone
      (VTD) as consolidation therapy in 24 Japanese patients with newly diagnosed MM.
      VTD consisted of bortezomib at a dose of 1.3 mg/m(2) and dexamethasone at a dose
      of 40 mg/day on days 1, 8, 15, and 22 of a 35-day cycle, with daily oral
      thalidomide at a dose of 100 mg/day. Grade 3-4 neutropenia and thrombocytopenia
      were documented in four and three patients (17 and 13 %), respectively, but drug
      dose reduction due to cytopenia was not required in any case. Peripheral
      neuropathy was common (63 %), but severe grade 3-4 peripheral neuropathy was not
      observed. Very good partial response or better response (>=VGPR) rates before and
      after consolidation therapy were 54 and 79 %, respectively. Patients had a
      significant probability of improving from <VGPR before consolidation therapy to
      >=VGPR after consolidation therapy (p = 0.041). The VTD regimen may be safe and
      effective as a consolidation therapy in the treatment of MM in Japanese
      population.

PMID- 24928524
TI  - Prenatal MRI evaluation of limb-body wall complex.
AB  - BACKGROUND: The sonographic (US) features of limb-body wall complex have been
      well documented; however the literature regarding the findings on MRI in limb
      body wall complex is scant. OBJECTIVE: To characterize the prenatal MRI features
      of limb-body wall complex. MATERIALS AND METHODS: We performed a retrospective
      review of all MRI scans of fetuses diagnosed with limb-body wall complex at our
      institution from 2001 to 2011. Fetuses without correlating US scans or follow-up
      information were excluded. Three pediatric radiologists blinded to the specific
      US findings reviewed the prenatal MRIs. Images were evaluated for the organ
      location and attachment, the body part affected, characterization of the body
      wall defect, and spinal, limb and umbilical cord abnormalities. RESULTS: Ten
      subjects met inclusion criteria. MRI was able to detect and characterize the body
      part affected and associated abnormalities. All fetuses had ventral wall defects,
      a small thorax and herniated liver and bowel. The kidneys were extracorporeal in
      three cases. The extruded organs were attached to the placenta or the uterine
      wall in all cases. Abnormal spinal curvatures of various degrees of severity were
      present in all cases. Eight cases had a short, uncoiled cord. Limb anomalies were
      present in 6 of the 10 cases. CONCLUSION: We illustrate the common fetal MRI
      findings of limb-body wall complex. The prenatal diagnosis of limb-body wall
      complex and the differentiation of this defect from treatable abdominal wall
      defects are crucial to providing appropriate guidance for patient counseling and
      management.

PMID- 24928525
TI  - Fat quantification and T2 measurement.

PMID- 24928526
TI  - Tamoxifen through GPER upregulates aromatase expression: a novel mechanism
      sustaining tamoxifen-resistant breast cancer cell growth.
AB  - Tamoxifen resistance is a major clinical challenge in breast cancer treatment.
      Aromatase inhibitors are effective in women who progressed or recurred on
      tamoxifen, suggesting a role of local estrogen production by aromatase in driving
      tamoxifen-resistant phenotype. However, the link between aromatase activity and
      tamoxifen resistance has not yet been reported. We investigated whether long-term
      tamoxifen exposure may affect aromatase activity and/or expression, which may
      then sustain tamoxifen-resistant breast cancer cell growth. We employed MCF-7
      breast cancer cells, tamoxifen-resistant MCF-7 cells (MCF-7 TR1 and TR2), SKBR-3
      breast cancer cells, cancer-associated fibroblasts (CAFs1 and CAFs2). We used
      tritiated-water release assay, realtime-RT-PCR, and immunoblotting analysis for
      evaluating aromatase activity and expression; anchorage-independent assays for
      growth; reporter-gene, electrophoretic-mobility-shift, and chromatin
      immunoprecipitation assays for promoter activity studies. We demonstrated an
      increased aromatase activity and expression, which supports proliferation in
      tamoxifen-resistant breast cancer cells. This is mediated by the G-protein
      coupled receptor GPR30/GPER, since knocking-down GPER expression or treatment
      with a GPER antagonist reversed the enhanced aromatase levels induced by long
      term tamoxifen exposure. The molecular mechanism was investigated in ER-negative,
      GPER/aromatase-positive SKBR3 cells, in which tamoxifen acts as a GPER agonist.
      Tamoxifen treatment increased aromatase promoter activity through an enhanced
      recruitment of c-fos/c-jun complex to AP-1 responsive elements located within the
      promoter region. As tamoxifen via GPER induced aromatase expression also in CAFs,
      this pathway may be involved in promoting aggressive behavior of breast tumors in
      response to tamoxifen treatment. Blocking estrogen production and/or GPER
      signaling activation may represent a valid option to overcome tamoxifen
      resistance in breast cancers.

PMID- 24928527
TI  - Effect of multifocality and multicentricity on outcome in early stage breast
      cancer: a systematic review and meta-analysis.
AB  - Women with multifocal or multicentric breast tumors (multifocality henceforth)
      have been reported to have greater probability of nodal metastasis and relapse
      and worse survival than women with unifocal tumors. However, these associations
      have been inconsistent and multifocality is not taken into account by staging
      guidelines and prognostic models. A systematic review of electronic databases
      identified publications exploring the association between multifocality and
      overall survival (OS), disease-free survival (DFS), disease-specific survival
      (DSS), and loco-regional relapse (LRR). The hazard ratios (HRs) for OS and DFS
      for multifocal compared to unifocal tumors were extracted from multivariable
      analyses and included in a meta-analysis. For studies not reporting multivariable
      analyses, odds ratios (OR) were estimated from Kaplan-Meier curves for all
      endpoints at 5 and 10 years. Twenty-two studies comprising 67,557 women were
      included. Multifocality was reported in 9.5 % of patients. Classical prognostic
      factors were well balanced between unifocal and multifocal populations. In
      multivariable analyses, multifocality was associated with significantly worse OS
      (HR 1.65; P = 0.02), and a non-significant association with worse DFS (HR 1.96; P
      = 0.07). In univariable analyses, multifocality was associated with worse OS,
      DFS, DSS, and LRR at 5 years (OR 1.39, P = 0.02; OR 1.52, P = 0.02; OR 1.56, P =
      0.03; and OR 3.23, P = 0.02, respectively). Similar estimates were observed at 10
      years, but statistical significance was only reached for DSS and LRR.
      Mutifocality appears to be associated with a worse prognosis, however,
      substantial inter-study heterogeneity limits the precise determination of
      increased risk. Further validation of the independent prognostic impact of
      multifocality is warranted.

PMID- 24928528
TI  - Expression profiles uncover the relationship between erythropoietin and cell
      proliferation in rat hepatocytes after a partial hepatectomy.
AB  - Erythropoietin (EPO) has a beneficial effect on hepatic cell proliferation during
      liver regeneration. However, the underlying mechanism has not yet been
      elucidated. To uncover the proliferation response of EPO in rat liver
      regeneration after partial hepatectomy (PH) at the cellular level, hepatocytes
      (HCs) were isolated using Percoll density gradient centrifugation. The genes of
      the EPO-mediated signaling pathway and the target genes of the transcription
      factor (TF) in the pathway were identified in a pathway and TF database search.
      Their expression profiles were then detected using Rat Genome 230 2.0 Microarray.
      The results indicated that the EPO-mediated signaling pathway is involved in 19
      paths and that 124 genes participate, of which 32 showed significant changes and
      could be identified as liver regeneration-related genes. In addition, 443 targets
      regulated by the TFs of the pathway and 60 genes associated with cell
      proliferation were contained in the array. Subsequently, the synergetic effect of
      these genes in liver regeneration was analyzed using the E(t) mathematical model
      based on their expression profiles. The results demonstrated that the E(t) values
      of paths 3, 8, 12 and 14-17 were significantly strengthened in the progressing
      phase of liver regeneration through the RAS/MEK/ERK or PI3K/AkappaT pathways. The
      synergetic effect of the target genes, in parallel with target-related cell
      proliferation, was also enhanced 12-72 h after PH, suggesting a potential
      positive effect of EPO on HC proliferation during rat liver regeneration. These
      data imply that the EPO receptor may allow EPO to promote HC proliferation
      through paths 3, 8, 12 and 14-17, mediating the RAS/MEK/ERK and PI3K/AkappaT
      pathways in rat liver regeneration after PH. 

PMID- 24928529
TI  - [Morbidity and mortality of surgically treated proximal humerus fractures].
AB  - BACKGROUND: The aim of the present study is to analyse the factors associated
      with mortality and the capacity to perform daily life activities (DLA) in
      patients with surgically treated proximal humeral fractures. METHODS: A
      retrospective study was conducted on 94 patients with a surgically treated
      proximal humeral fracture, with a mean follow-up of 8 years (2 - 12 years). A
      correlation analysis was performed to determine the relationship between the type
      of fracture, surgical technique, comorbidities and mortality and DLA. The Student
      t test was used for statistical analysis. RESULTS: A total of 72 patients were
      identified, 18.6% of them died during follow-up, all diagnosed with some
      comorbidity. There was no correlation between mortality, type of fracture or the
      technique used. Most of the patients (85.4%) had comorbidities, and 79.5% were
      completely independent for DLA. Although there was no relationship with the type
      of fracture, there was a significant reduction in the performing of DLA in
      patients treated with hemiarthroplasty, and in patients with neurological
      disorders. CONCLUSIONS: There was a mortality of 18.6% among patients with
      surgically treated proximal humerus fractures. The majority of surgically treated
      patients were fully independent for DLA at long-term follow-up.

PMID- 24928534
TI  - The Impact of Technical Assistance and Implementation Support on Program Capacity
      to Deliver Integrated Services.
AB  - This study assessed gains that New York State mental health and addiction
      outpatient clinics achieved in their capacity to provide integrated mental health
      and substance abuse services for persons with co-occurring disorders. The
      investigators used two Dual Diagnosis Capability (DDC) indices-one for Addiction
      Treatment (DDCAT) and one for Mental Health Treatment (DDCMHT)-to measure
      integration capability at baseline (n = 603) and at follow-up (n = 150), an
      average of 2 years post-baseline, during which time programs received technical
      assistance and implementation support. At baseline, the average program score was
      2.68, below the "Capable" level (3.0 on a 5-point scale). At follow-up, the
      average score was 3.04, and the percent of programs rated Capable more than
      doubled (from 22 to 52%). Programs with lower baseline scores and those with more
      time to follow-up (2-3 years) had the greatest increases, but 12 to 18 months
      were sufficient to realize sizeable and significant improvements. 

PMID- 24928535
TI  - The inhibition of constitutive androstane receptor-mediated pathway enhances the
      effects of anticancer agents in ovarian cancer cells.
AB  - BACKGROUND: Ovarian cancer is commonly treated with anticancer agents; however,
      many tumors become resistant. Resistance is regulated, in part, by P
      glycoprotein, which is encoded by the gene multiple drug resistance 1 (MDR1) and
      functions as a transmembrane efflux pump for the elimination of anticancer
      agents. Constitutive androstane receptor (CAR) is a nuclear receptor that
      regulates drug metabolism through control of MDR1 and other genes. PURPOSE: We
      examined whether the inhibition of CAR-mediated pathway could influence the
      cytotoxicity of three anticancer drugs, cisplatin, paclitaxel, and arsenic
      trioxide, in ovarian cancer cells. RESULTS: We observed that the cell
      proliferation of several ovarian cell lines expressing CAR significantly
      increased when CITCO was combined with anticancer agents compared with any
      anticancer agent alone. The up-regulation of MDR1 and UGT1A1 by anticancer agents
      was further enhanced in the presence of CITCO. We confirmed that combining CITCO
      with anticancer agents induced significantly lower levels of apoptosis than those
      achieved with any single anticancer drug. CAR down-regulation by RNA interference
      caused a significant increase in cell growth inhibition and enhancement of
      apoptosis in the presence of anticancer agents. Combination of CITCO with any
      anticancer agents significantly enhanced CAR-mediated transcription compared with
      any anticancer agents alone and CAR down-regulation completely inhibited the
      transcription in the presence of CITCO and/or anticancer agents. CONCLUSION:
      Inhibition of CAR pathway could be a novel therapeutic approach for the
      augmentation of sensitivity to anticancer agents, or to overcome resistance, in
      the treatment of ovarian cancer.

PMID- 24928536
TI  - Conserved regions of the DMD 3' UTR regulate translation and mRNA abundance in
      cultured myotubes.
AB  - Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease, is caused by
      mutations in the DMD gene, which encodes for the protein dystrophin. Its
      regulation is of therapeutic interest as even small changes in expression of
      functional dystrophin can significantly impact the severity of DMD. While tissue
      specific distribution and transcriptional regulation of several DMD mRNA isoforms
      has been well characterized, the post-transcriptional regulation of dystrophin
      synthesis is not well understood. Here, we utilize qRTPCR and a quantitative dual
      luciferase reporter assay to examine the effects of isoform specific DMD 5' UTRs
      and the highly conserved DMD 3' UTR on mRNA abundance and translational control
      of gene expression in C2C12 cells. The 5' UTRs were shown to initiate translation
      with low efficiency in both myoblasts and myotubes. Whereas, two large highly
      conserved elements in the 3' UTR, which overlap the previously described Lemaire
      A and D regions, increase mRNA levels and enhance translation upon
      differentiation of myoblasts into myotubes. The results presented here implicate
      an important role for DMD UTRs in dystrophin expression and delineate the cis
      acting elements required for the myotube-specific regulation of steady-state mRNA
      levels and translational enhancer activity found in the DMD 3' UTR. 

PMID- 24928537
TI  - 197th ENMC international workshop: Neuromuscular disorders of mitochondrial
      fusion and fission - OPA1 and MFN2 molecular mechanisms and therapeutic
      strategies: 26-28 April 2013, Naarden, The Netherlands.

PMID- 24928538
TI  - Purification, characterization, and crystallization of Crocodylus siamensis
      hemoglobin.
AB  - Crocodylus siamensis hemoglobin was purified by a size exclusion chromatography,
      Sephacryl S-100 with buffer containing dithiothreitol. The purified Hb was
      dissociated to be two forms (alpha chain and beta chain) which observed by SDS
      PAGE, indicated that the C. siamensis Hb was an unpolymerized form. The
      unpolymerized Hb (composed of two alpha chains and two beta chains) showed high
      oxygen affinity at 3.13 mmHg (P(50)) and 1.96 (n value), and a small Bohr effect
      (deltaH(+) = -0.29) at a pH of 6.9-8.4. Adenosine triphosphate did not affect the
      oxygenation properties, whereas bicarbonate ions strongly depressed oxygen
      affinity. Crude C. siamensis Hb solutions were showed high O(2) affinity at P(50)
      of 2.5 mmHg which may assure efficient utilization of the lung O(2) reserve
      during breath holding and diving. The purified Hbs were changed to
      cyanmethemoglobin forms prior crystallization. Rod- and plate-shaped crystals
      were obtained by the sitting-drop vapor-diffusion method at 5  degrees C using
      equal volumes of protein solution (37 mg/ml) and reservoir [10-13 % (w/v) PEG
      4000, with 0.1 M Tris buffer in present of 0.2 M MgCl(2).6H(2)O] solution at a pH
      of 7.0-8.5.

PMID- 24928539
TI  - Loop drainage of cutaneous abscesses using a modified sterile glove: a promising
      technique.
AB  - BACKGROUND: Cutaneous abscesses are a common clinical condition treated
      effectively with incision and drainage. OBJECTIVE: Placement of subcutaneous loop
      drains to facilitate healing of these infections has been described, but has yet
      to gain widespread adoption in clinical practice. DISCUSSION: This article
      includes instructions for how to perform this technique using materials available
      in the emergency setting, as well as a discussion of the potential advantages and
      disadvantages of this method. CONCLUSIONS: This technique of abscess management
      is effective and easy to perform. It offers potential benefits, such as decreased
      pain from packing material, no need for packing changes, and decreased need for
      follow-up visits.

PMID- 24928540
TI  - Patterns of injury and management of children with pelvic fractures at a non
      trauma center.
AB  - BACKGROUND: Pelvic injuries in young children are rare, and it has been difficult
      to establish clinical guidelines to assist providers in managing blunt pelvic
      trauma, especially in non-Level 1 trauma centers. OBJECTIVE: Our aim was to
      describe the relationship among clinical findings, mechanism of injury, and the
      radiographic resources utilized in children with pelvic fractures presenting to a
      non-Level 1 trauma center. METHODS: A retrospective review of patients with a
      pelvic fracture treated in two urban pediatric Level 3 emergency departments was
      performed. RESULTS: Between 2001 and 2010, a total of 208 patients were
      identified. Avulsion/iliac wing fractures were the most common fractures (58.7%),
      and sports-related injuries were the most common mechanism of injury (50.0%).
      Children with sports-related injuries were more likely to sustain an avulsion
      fracture (p<0.001), less likely to have a computed tomography scan obtained in
      the emergency department (p<0.001), and less likely to have an associated injury
      (p<0.001) than other children. Children struck by a motor vehicle (p<0.001) or
      involved in a motor vehicle accident (p<0.001) were more likely to receive a
      computed tomography scan (p<0.001) and have associated head and extremity
      injuries (p<0.001). Mechanism of injury was associated with abnormal computed
      tomography scans. Nearly all patients were treated nonoperatively (98.1%) and no
      deaths were reported in this study. CONCLUSIONS: Patterns of injury, based on
      mechanism of injury, have been reported to assist the assessment and management
      of children with minor pelvic injuries.

PMID- 24928541
TI  - Roosevelt-induced pneumonia.

PMID- 24928542
TI  - Perforated appendicitis diagnosed at the bedside.

PMID- 24928543
TI  - Emergency department management and follow-up of children with bicycle spoke
      injuries.
AB  - BACKGROUND: Evidence for a standard x-ray study and cast immobilization in
      emergency department (ED) management and follow-up of children with bicycle spoke
      injury (BSI) is absent. OBJECTIVE: To describe the injury pattern and outpatient
      follow-up and care of ED patients with BSI. In addition, patient characteristics
      predicting the presence of a fracture and long-term follow-up were assessed.
      METHODS: This was a retrospective study including BSI patients < 9 years of age.
      Kruskal-Wallis test was used to compare groups with a fracture, soft tissue
      injury, and mild skin abrasion. Multivariable logistic regression analysis was
      used to identify independent predictors of a fracture and long-term outpatient
      follow-up. RESULTS: Twenty-three percent of 141 included patients had a fracture,
      with a median (interquartile range) follow-up of 27 (23-40) days. For soft tissue
      injury and mild abrasions this was 9 (6-14) and 7 (5-9) days, respectively (p <
      0.001). No clinical variables could predict a fracture. Fifty-six (40%) patients
      required no further care after the first outpatient visit at ~1 week. Triage
      category yellow and swelling were independent predictors for more than one
      outpatient visit, besides presence of fracture. Corrected odds ratios (95%
      confidence interval) were 2.42 (0.99-5.88) and 4.76 (1.38-16.39), respectively.
      Only 12% of 141 patients had none of these predictors at ED presentation.
      CONCLUSIONS: A quarter of ED patients with BSI have a fracture with no clinical
      signs that could predict the presence of a fracture, justifying a standard x-ray
      study in ED management. Only 12% of ED patients with BSI have no fracture and no
      signs that predict long-term follow-up. In this group, further studies are
      warranted to investigate the benefit of cast immobilization for fractures and
      soft tissue injury.

PMID- 24928544
TI  - Left main coronary artery dissection in pediatric sport-related chest trauma.
AB  - BACKGROUND: Traumatic coronary artery dissection (CAD) after blunt chest trauma
      (BCT) is extremely rare, particularly in children. Among coronary dissections,
      left main coronary artery (LMCA) dissection is the least common, with only two
      pediatric cases reported previously. Manifestations of coronary dissections can
      range from ST segment changes to sudden death. However, these manifestations are
      not specific and can be present with other cardiac injuries. To our knowledge we
      present the first pediatric case of traumatic LMCA dissection after sport-related
      BCT that was treated successfully with coronary stenting. CASE REPORT: A 14-year
      old child sustained BCT during a baseball game. Early in the clinical course, he
      had episodes of ventricular dysrhythmias, diffuse ST changes, rising troponin I,
      and hemodynamic instability. Emergent cardiac catheterization revealed an LMCA
      dissection with extension into the proximal left anterior descending artery
      (LADA). A bare metal stent was placed from the LMCA to the LADA, which improved
      blood flow through the area of dissection. He has had almost full recovery of
      myocardial function and has been managed as an outpatient with oral heart failure
      and antiplatelet medications. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: Our case highlights that CAD, although rare, can occur after pediatric
      BCT. Pediatric emergency responders must have a heightened awareness that
      evidence of ongoing myocardial ischemia, such as evolving and focal myocardial
      infarction on electrocardiogram, persistent elevation or rising troponin I, and
      worsening cardiogenic shock, can represent a coronary event and warrant further
      evaluation. Cardiac catheterization can be both a diagnostic and therapeutic
      modality in such cases. Early recognition and management is vital for myocardial
      recovery.

PMID- 24928545
TI  - Influence of comorbid alcohol use disorder on treatment response of depressive
      patients.
AB  - Patients with major depressive disorder (MDD) frequently also have alcohol use
      disorder (AUD) and they are more likely to experience symptomatic recurrence and
      resist treatment. How the two disorders interrelate has not yet been fully
      examined in Japanese subjects. The treatment response of 47 MDD patients was
      followed for 12 weeks. Depressive symptoms were rated by the 17-item Hamilton
      Rating Scale for Depression (HAM-D) and those whose HAM-D score was less than 16
      were excluded. The MDD patients were divided into a non-alcohol use disorder
      (NAUD) and an alcohol use disorder (AUD) group according to the Alcohol Use
      Disorder Identification Test (AUDIT). We applied a cutoff score of 12 in the
      AUDIT scale. After 8 weeks, HAM-D NAUD group scores were significantly lower
      compared with AUD patients. The NAUD group, 23 individuals, prescribed
      therapeutic doses of antidepressant (equivalent to more than 150 mg of imipramine
      per day) significantly improved their HAM-D scores but no improvement occurred in
      the AUD subjects. Correlation analysis in all subjects revealed a significant
      negative correlation between AUDIT score and improved HAM-D score at endpoint.
      Moreover, a significant negative correlation was found between total alcohol
      consumption during the study period and improvement of HAM-D score at endpoint in
      AUD patients. These results suggest that co-occurrence of MDD and AUD is
      associated with a lower response to antidepressant treatment and it may reflect
      an inhibitory effect of ethanol on antidepressants action in the brain.

PMID- 24928547
TI  - Enhanced expression of GCRV VP6 in CIK cells by relative sequence optimization.
AB  - Efficient expression of target protein is one of strategies for gene therapy or
      vaccine design. Many studies showed that codon optimization could enhance the
      expression of target proteins. In this paper, a target sequence of about 1.26 kb
      encoding the major capsid protein VP6 of grass carp reovirus (GCRV) and an
      optimized counterpart were synthesized and inserted into vectors for expressing
      VP6. The final constructs (named as pcDV6G and pcDV6YG) were transfected in
      Ctenopharyngodon idellus kidney (CIK) cells. The fluorescence analysis and the
      Western blot results showed that the gene fragment was transfected and expressed
      in CIK cells successfully. Although the qRT-PCR results showed no difference at
      the messenger RNA (mRNA) levels between the different versions of vp6 in the
      indicated stages, the enzyme-linked immunosorbent assay (ELISA) results showed
      that the protein level of VP6 expressed by pcDV6YG was higher than that by pcDV6G
      in the indicated hours. Taken together, these results suggest that the enhanced
      expression of GCRV VP6 in CIK cells by relative sequence optimization may be a
      good choice for making DNA vaccine against GCRV.

PMID- 24928546
TI  - Lipid production by Cryptococcus curvatus on hydrolysates derived from corn fiber
      and sweet sorghum bagasse following dilute acid pretreatment.
AB  - Corn fiber and sweet sorghum bagasse (SSB) are both pre-processed lignocellulosic
      materials that can be used to produce liquid biofuels. Pretreatment using dilute
      sulfuric acid at a severity factor of 1.06 and 1.02 released 83.2 and 86.5 % of
      theoretically available sugars out of corn fiber and SSB, respectively. The
      resulting hydrolysates derived from pretreatment of SSB at SF of 1.02 supported
      growth of Cryptococcus curvatus well. In 6 days, the dry cell density reached
      10.8 g/l with a lipid content of 40 % (w/w). Hydrolysates from corn fiber,
      however, did not lead to any significant cell growth even with addition of
      nutrients. In addition to consuming glucose, xylose, and arabinose, C. curvatus
      also utilized formic acid, acetic acid, 4-hydroxymethylfurfural, and levulinic
      acid for growth. Thus, C. curvatus appeared to be an excellent yeast strain for
      producing lipids from hydrolysates developed from lignocellulosic feedstocks.

PMID- 24928548
TI  - Gene expression analysis in MCF-7 breast cancer cells treated with recombinant
      bromelain.
AB  - The contributing molecular pathways underlying the pathogenesis of breast cancer
      need to be better characterized. The principle of our study was to better
      understand the genetic mechanism of oncogenesis for human breast cancer and to
      discover new possible tumor markers for use in clinical practice. We used
      complimentary DNA (cDNA) microarrays to compare gene expression profiles of
      treated Michigan Cancer Foundation-7 (MCF-7) with recombinant bromelain and
      untreated MCF-7. SpringGene analysis was carried out of differential expression
      followed by Ingenuity Pathway Analysis (IPA), to understand the underlying
      consequence in developing disease and disorders. We identified 1,102 known genes
      differentially expressed to a significant degree (p<0.001) changed between the
      treatment. Within this gene set, 20 genes were significantly changed between
      treated cells and the control cells with cutoff fold change of more than 1.5.
      These genes are RNA-binding motif, single-stranded interacting protein 1 (RBMS1),
      ribosomal protein L29 (RPL29), glutathione S-transferase mu 2 (GSTM2), C15orf32,
      Akt3, B cell translocation gene 1 (BTG1), C6orf62, C7orf60, kinesin-associated
      protein 3 (KIFAP3), FBXO11, AT-rich interactive domain 4A (ARID4A), COPS2,
      TBPL1|SLC2A12, TMEM59, SNORD46, glioma tumor suppressor candidate region gene 2
      (GLTSCR2), and LRRFIP. Our observation on gene expression indicated that
      recombinant bromelain produces a unique signature affecting different pathways,
      specific for each congener. The microarray results give a molecular mechanistic
      insight and functional effects, following recombinant bromelain treatment. The
      extent of changes in genes is related to and involved significantly in gap
      junction signaling, amyloid processing, cell cycle regulation by BTG family
      proteins, and breast cancer regulation by stathmin1 that play major roles.

PMID- 24928549
TI  - Enhancing performance of uricase using multiwalled carbon nanotube doped
      polyaniline.
AB  - Multiwalled carbon nanotubes (CNT) doped polyaniline (Pani) nanocomposite has
      been electrochemically deposited onto indium tin oxide (ITO)-coated glass
      substrate for fabrication of uric acid biosensor. To achieve this, uricase (from
      Bacillus fastidiosus) has been covalently immobilized onto glutaraldehyde
      modified CNT-Pani/ITO and characterized using cyclic voltammetry (CV), scanning
      electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy,
      electrochemical impedance spectroscopy (EIS), etc. CV studies of CNT-Pani/ITO
      electrode reveals that the system obeys quasi-reversible electron transfer
      behavior with diffusion coefficient of 2.3346 * 10(-8) cm s(-1) in K3FeCN6.
      Fabricated uricase-CNT-Pani/ITO electrodes were tested for uric acid detection in
      buffer and spiked serum samples electrochemically. It was found that fabricated
      electrode was able to detect 0.01-1.0 mM uric acid using CV and 0.02-0.8 mM uric
      acid using differential pulse voltammetry (DPV). The enhanced electrochemical
      performance of this biosensor is due to the high enzyme loading synergistically
      connected to CNT-Pani nanocomposite leading to improved enzyme characteristics
      such as Km value of 4.85 * 10(-3) mM L(-1) (about 70 times less than the free
      enzyme), sensitivity of 43.2 MUA mM(-1) for CV-based detection and 8.38 MUA mM(
      1) for DPV-based detection within response time of 60 s. Fabricated electrodes
      were able to maintain their electrochemical activity with 60 times reusability
      and were stable up to 28 weeks when stored at 4  degrees C. 

PMID- 24928550
TI  - Synthesis and characterization of reduced graphene oxide supported gold
      nanoparticles-poly(pyrrole-co-pyrrolepropylic acid) nanocomposite-based
      electrochemical biosensor.
AB  - A conducting poly(pyrrole-co-pyrrolepropylic acid) copolymer nanocomposite film
      (AuNP-PPy-PPa) incorporating gold nanoparticles (AuNP) was electrochemically
      grown using a single step procedure over electrochemically reduced graphene oxide
      (RGO) flakes deposited on a silane-modified indium-tin-oxide (ITO) glass plate.
      The RGO support base provided excellent mechanical and chemical stability to the
      polymer nanocomposite matrix. The porous nanostructure of AuNP-PPy-PPa/RGO
      provided a huge accessible area to disperse AuNP, and it avoided metallic
      agglomeration within the polymer matrix. The AuNP-PPy-PPa/RGO was characterized
      by high-resolution transmission electron microscopy (HRTEM), contact angle
      measurements, Fourier transform infrared spectroscopy (FTIR), and electrochemical
      techniques. The pendant carboxyl group of AuNP-PPy-PPa/RGO was covalently bonded
      with myoglobin protein antibody, Ab-Mb, for the construction of a bioelectrode.
      Electrochemical impedance spectroscopy technique was used for the
      characterization of the bioelectrode and as an impedimetric biosensor for the
      detection of human cardiac biomarker, Ag-cMb. The bioelectrode exhibited a linear
      impedimetric response to Ag-cMb in the range of 10 ng mL(-1) to 1 MUg mL(-1), in
      phosphate-buffered solution (PBS) (pH 7.4, 0.1 M KCl) with a sensitivity of 92.13
      Omega cm(2) per decade. 

PMID- 24928551
TI  - Moderate drought causes dramatic floral transcriptomic reprogramming to ensure
      successful reproductive development in Arabidopsis.
AB  - BACKGROUND: Drought is a major constraint that leads to extensive losses to
      agricultural yield worldwide. The potential yield is largely determined during
      inflorescence development. However, to date, most investigations on plant
      response to drought have focused on vegetative development. This study describes
      the morphological changes of reproductive development and the comparison of
      transcriptomes under various drought conditions. RESULTS: The plants grown were
      studied under two drought conditions: minimum for successful reproduction (45-50%
      soil water content, moderate drought, MD) and for survival (30-35%, severe
      drought, SD). MD plants can produce similar number of siliques on the main stem
      and similar number of seeds per silique comparing with well-water plants. The
      situation of SD plants was much worse than MD plants. The transcriptomes of
      inflorescences were further investigated at molecular level using microarrays.
      Our results showed more than four thousands genes with differential expression
      under severe drought and less than two thousand changed under moderate drought
      condition (with 2-fold change and q-value < 0.01). We found a group of genes with
      increased expression as the drought became more severe, suggesting putative
      adaptation to the dehydration. Interestingly, we also identified genes with
      alteration only under the moderate but not the severe drought condition,
      indicating the existence of distinct sets of genes responsive to different levels
      of water availability. Further cis-element analyses of the putative regulatory
      sequences provided more information about the underlying mechanisms for
      reproductive responses to drought, suggesting possible novel candidate genes that
      protect those developing flowers under drought stress. CONCLUSIONS: Different
      pathways may be activated in response to moderate and severe drought in
      reproductive tissues, potentially helping plant to maximize its yield and balance
      the resource consumption between vegetative and reproductive development under
      dehydration stresses.

PMID- 24928552
TI  - DHEA effects on brain and behavior: insights from comparative studies of
      aggression.
AB  - Historically, research on the neuroendocrinology of aggression has been dominated
      by the paradigm that the brain receives sex steroid hormones, such as
      testosterone (T), from the gonads, and then these gonadal hormones modulate
      behaviorally relevant neural circuits. While this paradigm has been extremely
      useful for advancing the field, recent studies reveal important alternatives. For
      example, most vertebrate species are seasonal breeders, and many species show
      aggression outside of the breeding season, when the gonads are regressed and
      circulating levels of gonadal steroids are relatively low. Studies in diverse
      avian and mammalian species suggest that adrenal dehydroepiandrosterone (DHEA),
      an androgen precursor and prohormone, is important for the expression of
      aggression when gonadal T synthesis is low. Circulating DHEA can be converted
      into active sex steroids within the brain. In addition, the brain can synthesize
      sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels
      from circulating steroid levels. These alternative mechanisms to provide sex
      steroids to specific neural circuits may have evolved to avoid the costs of high
      circulating T levels during the non-breeding season. Physiological indicators of
      season (e.g., melatonin) may allow animals to switch from one neuroendocrine
      mechanism to another across the year. DHEA and neurosteroids are likely to be
      important for the control of multiple behaviors in many species, including
      humans. These studies yield fundamental insights into the regulation of DHEA
      secretion, the mechanisms by which DHEA affects behavior, and the brain regions
      and neural processes that are modulated by DHEA. It is clear that the brain is an
      important site of DHEA synthesis and action. This article is part of a Special
      Issue entitled 'Essential role of DHEA'. 

PMID- 24928554
TI  - "There's No Correspondence Between Me and My Age": Old Age in Theresia Walser's
      King Kong's Daughters.
AB  - PURPOSE OF THE STUDY: Against the context of a rapidly aging population, the
      theme of senescence has been figuring increasingly prominently in contemporary
      German theater. This paper discusses the depiction of old age in one notable
      example, Theresia Walser's King Kong's Daughters, a hugely successful black
      comedy set in a nursing home. DESIGN AND METHODS: This paper takes an
      interdisciplinary approach in its analysis of Walser's play, drawing not just on
      drama and theater studies, but also on performance, film, and cultural studies as
      well as the sociology and psychology of aging. RESULTS: King Kong's Daughters
      might seem to be pervaded with negative ageist stereotypes. It is argued here,
      however, that Walser skillfully exploits the special formal qualities of
      theatrical performance--in particular, its liveness, corporeality, and
      communality--to illuminate both what it is like to be old and what it is like to
      care for the elderly in today's world. IMPLICATIONS: Given demographic
      developments, senescence seems set to increasingly inform the themes, motifs, and
      characters of theater in Germany and beyond. Paying closer attention to how old
      age is invoked on the contemporary stage can generate insights that are not only
      of interest to theater scholars, but are also of value to gerontologists and age
      scholars more generally.

PMID- 24928555
TI  - Promoting and Protecting Against Stigma in Assisted Living and Nursing Homes.
AB  - PURPOSE OF THE STUDY: To determine the extent to which structures and processes
      of care in multilevel settings (independent living, assisted living, and nursing
      homes) result in stigma in assisted living and nursing homes. DESIGN AND METHODS:
      Ethnographic in-depth interviews were conducted in 5 multilevel settings with 256
      residents, families, and staff members. Qualitative analyses identified the
      themes that resulted when examining text describing either structures of care or
      processes of care in relation to 7 codes associated with stigma. RESULTS: Four
      themes related to structures of care and stigma were identified, including the
      physical environment, case mix, staff training, and multilevel settings; five
      themes related to processes of care and stigma, including dining, independence,
      respect, privacy, and care provision. For each theme, examples were identified
      illustrating how structures and processes of care can potentially promote or
      protect against stigma. IMPLICATIONS: In no instance were examples or themes
      identified that suggested the staff intentionally promoted stigma; on the other
      hand, there was indication that some structures and processes were intentionally
      in place to protect against stigma. Perhaps the most important theme is the
      stigma related to multilevel settings, as it has the potential to reduce
      individuals' likelihood to seek and accept necessary care. Results suggest
      specific recommendations to modify care and reduce stigma.

PMID- 24928553
TI  - Vaccination in the elderly: what can be recommended?
AB  - The age-associated increased susceptibility to infectious disease would suggest
      that vaccination should be a route to promote healthy aging and keep our seniors
      autonomous and independent. While vaccination represents a cost-effective and
      efficient strategy at community level, the ability of the immune system to mount
      a protective immune response is still unpredictable at the level of the
      individual. Thus, at a similar age, some individuals, including the elderly,
      might still be 'good' responders while some other, even younger, would definitely
      fail to mount a protective response. In this review, the current burden of
      vaccine-preventable diseases in the aging and aged population will be detailed
      with the aim to identify the ideal vaccine candidates over the age of 50 years.
      This article will conclude with potential strategies to reduce, as best as
      possible, this burden and the imperative need to overcome barriers in extending
      current vaccine coverage towards to a lifelong vaccine schedule. 

PMID- 24928557
TI  - Training Older Adults to Use Tablet Computers: Does It Enhance Cognitive
      Function?
AB  - PURPOSE OF THE STUDY: Recent evidence shows that engaging in learning new skills
      improves episodic memory in older adults. In this study, older adults who were
      computer novices were trained to use a tablet computer and associated software
      applications. We hypothesize that sustained engagement in this mentally
      challenging training would yield a dual benefit of improved cognition and
      enhancement of everyday function by introducing useful skills. DESIGN AND
      METHODS: A total of 54 older adults (age 60-90) committed 15 hr/week for 3
      months. Eighteen participants received extensive iPad training, learning a broad
      range of practical applications. The iPad group was compared with 2 separate
      controls: a Placebo group that engaged in passive tasks requiring little new
      learning; and a Social group that had regular social interaction, but no active
      skill acquisition. All participants completed the same cognitive battery pre- and
      post-engagement. RESULTS: Compared with both controls, the iPad group showed
      greater improvements in episodic memory and processing speed but did not differ
      in mental control or visuospatial processing. IMPLICATIONS: iPad training
      improved cognition relative to engaging in social or nonchallenging activities.
      Mastering relevant technological devices have the added advantage of providing
      older adults with technological skills useful in facilitating everyday activities
      (e.g., banking). This work informs the selection of targeted activities for
      future interventions and community programs.

PMID- 24928558
TI  - Patterns of failure after intensity-modulated radiotherapy in head and neck
      squamous cell carcinoma using compartmental clinical target volume delineation.
AB  - AIMS: To determine the pattern of disease recurrence in non-nasopharyngeal head
      and neck squamous cell carcinoma (HNSCC) patients treated with radical intensity
      modulated radiotherapy (IMRT) with or without chemotherapy, and to correlate the
      sites of locoregional recurrence with radiotherapy target volumes. MATERIALS AND
      METHODS: In total, 136 patients treated with radical IMRT with or without
      chemotherapy between 2008 and 2011 for non-nasopharyngeal HNSCC were
      retrospectively identified. A compartmental approach to clinical target volume
      (CTV) delineation was routinely utilised during this period and IMRT was
      delivered using a 5-7 angle step and shoot technique. Locoregional recurrences
      were reconstructed on the planning computed tomography scan by both deformable
      image coregistration and by visual assessment, and were analysed in relation to
      target volumes and dosimetry. RESULTS: The median follow-up was 31 (range 3-53)
      months. Two year local control, regional control, disease-free survival, distant
      metastasis-free survival and overall survival were 86, 93, 78, 89 and 79%,
      respectively. One hundred and twenty of 136 (88%) patients achieved a complete
      response to treatment and 7/120 (6%) have subsequently had a locoregional
      recurrence. Analysis of these recurrences revealed five to be infield; one to be
      marginal to the high-dose CTV; one to be out-of-field. Overall the marginal/out
      of-field recurrence rate was 2/136 (1.5%). CONCLUSIONS: IMRT utilising a
      compartmental approach to CTV delineation was associated with a low rate of
      marginal/out-of-field recurrence.

PMID- 24928559
TI  - Detecting overlapping protein complexes based on a generative model with
      functional and topological properties.
AB  - BACKGROUND: Identification of protein complexes can help us get a better
      understanding of cellular mechanism. With the increasing availability of large
      scale protein-protein interaction (PPI) data, numerous computational approaches
      have been proposed to detect complexes from the PPI networks. However, most of
      the current approaches do not consider overlaps among complexes or functional
      annotation information of individual proteins. Therefore, they might not be able
      to reflect the biological reality faithfully or make full use of the available
      domain-specific knowledge. RESULTS: In this paper, we develop a Generative Model
      with Functional and Topological Properties (GMFTP) to describe the generative
      processes of the PPI network and the functional profile. The model provides a
      working mechanism for capturing the interaction structures and the functional
      patterns of proteins. By combining the functional and topological properties, we
      formulate the problem of identifying protein complexes as that of detecting a
      group of proteins which frequently interact with each other in the PPI network
      and have similar annotation patterns in the functional profile. Using the idea of
      link communities, our method naturally deals with overlaps among complexes. The
      benefits brought by the functional properties are demonstrated by real data
      analysis. The results evaluated using four criteria with respect to two gold
      standards show that GMFTP has a competitive performance over the state-of-the-art
      approaches. The effectiveness of detecting overlapping complexes is also
      demonstrated by analyzing the topological and functional features of multi- and
      mono-group proteins. CONCLUSIONS: Based on the results obtained in this study,
      GMFTP presents to be a powerful approach for the identification of overlapping
      protein complexes using both the PPI network and the functional profile. The
      software can be downloaded from
      http://mail.sysu.edu.cn/home/stsddq@mail.sysu.edu.cn/dai/others/GMFTP.zip.

PMID- 24928560
TI  - Predictive value of fractional nitric oxide in asthma diagnosis-subgroup
      analyses.
AB  - BACKGROUND: There are no studies investigating the benefit of using FeNO
      measurements in correlation with sensitization to perennial and seasonal
      allergens in children with asthma. OBJECTIVE: To define the group of children
      with respiratory symptoms in whose FeNO measurement has predictive value for
      asthma. We assessed the effect of age, allergy profile, atopy, lung function and
      the presence of allergic rhinitis on interpretation of FeNO levels for clinical
      applications. METHODS: It was a retrospective, cross-sectional study. We
      evaluated data from medical documentation of 1767 children with symptoms of
      allergic diseases such as asthma and/or allergic rhinitis. We included in the
      analyses subjects who had the following tests done during diagnostic procedures
      (single measurement): FeNO, spirometry, specific IgE results. All subjects had
      undergone a minimum 3-years prospective clinical observation after the first FeNO
      measurement until the later assignment (or not) of an asthma/allergic rhinitis
      diagnosis. RESULTS: We included 1767 children into the analysis; asthma diagnosis
      was confirm in 1054 (59.6%) children. We showed that only atopy (OR: 1.9; 95%CI:
      1.5-2.4) and presence of allergic rhinitis (OR: 1.6; 95%CI: 1.4-1.9) were
      independently associated with increased FeNO level. Only among patients with
      atopy and allergic rhinitis FeNO level (above 23 ppb) was associated with asthma
      diagnosis. Sensitivity, specificity, positive predictive value and negative
      predictive value of FeNO >23 ppb for asthma diagnosis were as follows: 0.9(95%CI:
      0.68-0.98), 0.52(95%CI: 0.42-0.61), 0.25(95%CI: 0.16-0.37), 0.97(95%CI: 0.88
      0.99). CONCLUSION: We showed that in children with atopy and with allergic
      rhinitis a negative predictive value for asthma diagnosis was very high with the
      optimal cut-off point of FeNO 23 ppb. Therefore we showed the utility of FeNO
      measurements to exclude asthma in the subgroup of patients with atopy and
      allergic rhinitis.

PMID- 24928561
TI  - Controversies and conundrums in hydrogen sulfide biology.
AB  - Hydrogen sulfide (H2S) signaling has been implicated in physiological processes
      in practically all organ systems studied to date. At times the excitement of this
      new field has outpaced the technical expertise or practical knowledge with which
      to accurately assess these advancements. Recently, the myriad of proposed H2S
      actions has spawned interest in using indicators of H2S metabolism, especially
      plasma H2S concentrations, as a means of identifying a variety of
      pathophysiological conditions or to predict clinical outcomes. While this is a
      noteworthy endeavor, there are a number of contraindications to this practice at
      this time. First, there is little consensus regarding normal, i.e.,
      "physiological" concentrations of H2S in either plasma or tissue. In fact, it has
      been shown that the methods most often employed for these measurements are
      associated with substantial artifact. Second, interactions, or presumed lack
      thereof, of H2S with other biomolecules (e.g., O2, H2O2, pH, etc.) or analytical
      reagents (e.g., reducing reagents, N-ethylmaleimide, phenylarsine, etc.) are
      often assumed but not evaluated. Third, the experimental design and/or
      statistical analyses may not be sufficient to justify using H2S concentration in
      tissue or blood as a predictive biomarker of pathophysiology. In this study, we
      first briefly review the problems associated with plasma and tissue H2S
      measurements and the associated errors and we provide some simple methods to
      evaluate whether the data obtained is physiologically relevant. Second we provide
      a brief analysis of H2S interactions with the above biomolecules. Third, we
      provide a statistical tool with which to determine the clinical applicability of
      H2S measurements. It is hoped that these points will provide a rational
      background for future work. 

PMID- 24928562
TI  - Oxidation of hydrogen sulfide by human liver mitochondria.
AB  - Hydrogen sulfide (H2S) is the third gasotransmitter discovered. Sulfide shares
      with the two others (NO and CO) the same inhibiting properties towards
      mitochondrial respiration. However, in contrast with NO or CO, sulfide at
      concentrations lower than the toxic (MUM) level is an hydrogen donor and a
      substrate for mitochondrial respiration. This is due to the activity of a sulfide
      quinone reductase found in a large majority of mitochondria. An ongoing study of
      the metabolic state of liver in obese patients allowed us to evaluate the sulfide
      oxidation capacity with twelve preparations of human liver mitochondria. The
      results indicate relatively high rates of sulfide oxidation with a large
      variability between individuals. These observations made with isolated
      mitochondria appear in agreement with the main characteristics of sulfide
      oxidation as established before with the help of cellular models. 

PMID- 24928563
TI  - Walnut anaphylaxis: the usefulness of molecular-based allergy diagnostics.

PMID- 24928564
TI  - Utility and importance of animal data in drug product labels.
AB  - Information on the use and safety of medicines to assist prescription by
      healthcare professionals occurs in drug labels (Summary of Product
      Characteristics in Europe and Package Insert in the USA). Animal data (notably
      genotoxicity, reproduction toxicity and carcinogenicity and/or repeat dose
      toxicity testing) comprise an important component of the information (having a
      vital role in giving assurance that an extensive safety assessment for the
      medicinal product has occurred) and regulatory guidance is available to help
      inform on its input into drug labels. However, an evaluation of animal data for
      the 27 new drugs approved in the USA in 2013 (and the same drugs if available in
      Europe) shows great variability in detail and level of information presented
      within and across regions and/or the possibility of confusion on interpretation
      of some of the presented animal study findings. It is concluded that it may be
      time to revisit what animal data are presented in drug product labels (although
      bearing in mind current regional regulatory guidance requirements), not only to
      allow within and across region consistency on information given but to present it
      in a way that fully assists healthcare professions when prescribing a medicine.

PMID- 24928565
TI  - Towards AOP application--implementation of an integrated approach to testing and
      assessment (IATA) into a pipeline tool for skin sensitization.
AB  - Since the OECD published the Adverse Outcome Pathway (AOP) for skin
      sensitization, many efforts have focused on how to integrate and interpret
      nonstandard information generated for key events in a manner that can be
      practically useful for decision making. These types of frameworks are known as
      Integrated Approaches to Testing and Assessment (IATA). Here we have outlined an
      IATA for skin sensitization which focuses on existing information including non
      testing approaches such as QSAR and read-across. The IATA was implemented into a
      pipeline tool using OASIS technology to provide a means of systematically
      collating and compiling relevant information which could be used in an assessment
      of skin sensitization potential. A test set of 100 substances with available skin
      sensitization information was profiled using the pipeline IATA. In silico and in
      chemico profiling information alone was able to correctly predict skin
      sensitization potential, with a preliminary accuracy of 73.85%. Information from
      other relevant endpoints (e.g., Ames mutagenicity) was found to improve the
      accuracy (to 87.6%) when coupled with a reaction chemistry mechanistic
      understanding. This pipeline platform could be useful in the assessment of skin
      sensitization potential and marks a step change in how non testing approaches can
      be practically applied.

PMID- 24928566
TI  - Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product
      derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.
AB  - CMS-1, mainly composed of imperatorin as its active compound, is a partially
      purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has
      the potential to be further developed as a new treatment for hypertension. Thus,
      we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0
      900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive
      days, followed by a 15-day recovery period. The major target organs of CMS-1
      toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme
      elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and
      P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters
      disturbances) systems. Most treatment-induced adverse effects were reversible or
      showed a progressive recovery upon discontinuation of the treatment. The No
      Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day
      for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in
      patients should focus on the gastrointestinal system, blood tests for liver
      functions, electrolytes, and blood homeostasis, cardiovascular functions, and
      immune functions.

PMID- 24928567
TI  - Differences in patient ratings of medical home domains among adults with
      diabetes: comparisons across primary care sites.
AB  - BACKGROUND: There is growing and sustained recognition that Patient-Centered
      Medical Homes (PCMHs) represent a viable approach to dealing with the
      fragmentation of care faced by many individuals, including those living with
      diabetes. The National Committee for Quality Assurance (NCQA) has spearheaded a
      program that recognizes medical practices that adopt key elements of the PCMH.
      Even though practices can achieve the same level of recognition, it is unclear
      whether all PCMHs deliver care in the same manner and how these differences can
      be associated with patient ratings of their experience with care. METHODS: This
      study uses a mixed-methods approach to explore differences in care delivery
      across 4 NCQA level 3 recognized PCMHs located in a southern state. Furthermore,
      the study examines the association between each clinic and patient ratings of key
      PCMH domains. The qualitative component of the study included in-depth interviews
      with medical directors at each site in order to determine how the PCMH at each
      clinic was operationalized. In addition, 1300 adult patients with diabetes were
      surveyed about their experiences with their PCMH. Bivariate and ordinal
      logistical analyses were conducted to determine how PCMH experiences varied
      across the 4 clinics. RESULTS: The in-depth interviews revealed that one clinic
      (clinic 1) had a stronger primary care orientation relative to the other
      locations. Furthermore, patients at these clinics were more likely to provide
      higher ratings of care across all PCMH domains. CONCLUSIONS: This study
      demonstrates that not all PCMH clinics are alike and that these differences can
      possibly affect patient perceptions of their care.

PMID- 24928568
TI  - Unravelling emotional viewpoints on a bio-based economy using Q methodology.
AB  - A transition to a bio-based economy will affect society and requires collective
      action from a broad range of stakeholders. This includes the public, who are
      largely unaware of this transition. For meaningful public engagement people's
      emotional viewpoints play an important role. However, what the public's emotions
      about the transition are and how they can be taken into account is underexposed
      in public engagement literature and practice. This article aims to unravel the
      public's emotional views of the bio-based economy as a starting point for public
      engagement. Using Q methodology with visual representations of a bio-based
      economy we found four emotional viewpoints: (1) compassionate environmentalist,
      (2) principled optimist, (3) hopeful motorist and (4) cynical environmentalist.
      These provide insight into the distinct and shared ways through which members of
      the public connect with the transition. Implications for public engagement are
      discussed. 

PMID- 24928569
TI  - Audience reach of science on television in 10 European countries: An analysis of
      people-meter data.
AB  - Beginning with a differentiation of science programmes into five different
      editorial concepts, this article explores the audience reach of science on
      television in 10 European countries with a special emphasis on young audiences
      aged between 14 and 29 years. In relation to the share of this age group in the
      entire population, science programmes in all countries reach a considerably
      smaller proportion of younger viewers. Specific preferences for science content
      on television do not seem to be relevant in explaining aggregated viewing
      behaviours especially of young audiences. Unlike all other segments, the young
      science viewer segment is almost intangible as an aggregated group, as a
      definable segment of a mass audience that can be targeted by science programme
      makers. 

PMID- 24928572
TI  - Postsystolic shortening by myocardial deformation imaging as a sign of cardiac
      adaptation to pressure overload in fetal growth restriction.
AB  - BACKGROUND: Fetal growth restriction (FGR) is associated with global adverse
      cardiac remodeling in utero and increased cardiovascular mortality in adulthood.
      Prenatal myocardial deformation has not been evaluated in FGR to date. We aimed
      to evaluate prenatal cardiac remodeling comprehensively in FGR including
      myocardial deformation imaging. METHODS AND RESULTS: Echocardiography was
      performed in 37 consecutive FGR (defined as birthweight <10th centile) and 37
      normally grown fetuses. A comprehensive fetal echocardiography was performed
      including tissue Doppler and 2-dimensional-derived strain and strain rate.
      Postnatal blood pressure measurement at 6 months of age was also performed. FGR
      cases showed signs of more globular hearts with decreased longitudinal motion
      (left systolic annular peak velocity: controls mean 6 cm/s [SD 1.2] versus FGR
      5.3 [1]) and diastolic dysfunction (isovolumic relaxation time: controls 44 ms
      [6] versus FGR 52 [9]). Peak strain and strain rate values of the left ventricle
      were not significantly different; however, a postsystolic shortening in the basal
      segment of the septal ventricular wall was observed in 57% of the FGR cases and
      in none of controls (P<0.001). FGR cases with postsystolic shortening had absence
      of a hypertrophic response, a poorer perinatal outcome (lower gestational age and
      birthweight, containing all cases of perinatal mortality [8%]), and higher values
      of blood pressure. CONCLUSIONS: Myocardial deformation imaging revealed a
      postsystolic shortening in 57% of FGR, which supports increased pressure overload
      as a mechanism for cardiovascular programming in FGR. Postsystolic shortening was
      associated with severity and with higher blood pressure postnatally.

PMID- 24928571
TI  - Role of GPR30 in mediating estradiol effects on acetylcholine release in the
      hippocampus.
AB  - We have hypothesized that estradiol enhances basal forebrain cholinergic function
      and cognitive performance, at least in part, via activation of the novel estrogen
      receptor GPR30. Here we evaluated the effects of estradiol, G-1 (a selective
      GPR30 agonist), and tamoxifen (TAM; an ERalpha/ERbeta antagonist that also acts
      as a GPR30 agonist), on acetylcholine (ACh) release in the hippocampus, as well
      as the ability to block the effects of 17beta-estradiol (E) or TAM with the GPR30
      antagonist G-15. Note that G-1 was included to evaluate the effects of
      selectively activating GPR30, whereas TAM was included to differentiate effects
      of E associated with activation of GPR30 vs. ERalpha or ERbeta. The study was
      designed to test effects on potassium-stimulated release, as well as on ACh
      release stimulated by feeding. Effects of feeding were included because the tasks
      we used previously to demonstrate beneficial effects of E on cognitive
      performance were motivated by food reward, and we hypothesized that E may enhance
      performance by increasing ACh release in association with that reward.
      Ovariectomized rats were treated for 1week, and ACh release was evaluated using
      in vivo microdialysis. In addition, rats were fed at the same time daily for
      several days and were fasted overnight prior to microdialysis. For each rat, ACh
      release was evaluated under basal conditions, in response to feeding, and in
      response to elevated potassium. Both feeding and elevated potassium increased ACh
      release in the hippocampus. In response to feeding, E, G-1, and TAM all
      significantly increased the percent change in release. The effects of E and TAM
      were blocked by G-15, and the effects of combining E+TAM did not differ
      significantly from the effects of E or TAM alone. In response to elevated
      potassium, E, and TAM significantly increased the percent change in ACh release.
      G-1 produced a slightly lesser effect. The effect of TAM was reduced by G-15, but
      the effect of E was not. These findings suggest that activation of GPR30 is both
      necessary and sufficient to account for the effects of E on ACh release
      associated with feeding. In contrast, activation of GPR30 appears to be
      sufficient, but may not be necessary for increased release associated with
      elevated potassium. The changes associated with feeding are consistent with the
      effects of E, G-1 and G-15 on acquisition of a spatial learning task previously
      described. These data confirm and extend previous reports, and support a
      hypothesis wherein E treatment can improve learning on specific tasks by
      activating GPR30 and enhancing ACh release in association with food reward. 

PMID- 24928570
TI  - The perfume of reproduction in birds: chemosignaling in avian social life.
AB  - This article is part of a Special Issue "Chemosignals and Reproduction". Chemical
      cues were probably the first cues ever used to communicate and are still
      ubiquitous among living organisms. Birds have long been considered an exception:
      it was believed that birds were anosmic and relied on their acute visual and
      acoustic capabilities. Birds are however excellent smellers and use odors in
      various contexts including food searching, orientation, and also breeding.
      Successful reproduction in most vertebrates involves the exchange of complex
      social signals between partners. The first evidence for a role of olfaction in
      reproductive contexts in birds only dates back to the seventies, when ducks were
      shown to require a functional sense of smell to express normal sexual behaviors.
      Nowadays, even if the interest for olfaction in birds has largely increased, the
      role that bodily odors play in reproduction still remains largely understudied.
      The few available studies suggest that olfaction is involved in many reproductive
      stages. Odors have been shown to influence the choice and synchronization of
      partners, the choice of nest-building material or the care for the eggs and
      offspring. How this chemical information is translated at the physiological level
      mostly remains to be described, although available evidence suggests that, as in
      mammals, key reproductive brain areas like the medial preoptic nucleus are
      activated by relevant olfactory signals. Olfaction in birds receives increasing
      attention and novel findings are continuously published, but many exciting
      discoveries are still ahead of us, and could make birds one of the animal classes
      with the largest panel of developed senses ever described. 

PMID- 24928573
TI  - Muscle diseases: mimics and chameleons.
AB  - Muscle diseases are not as common as headaches and funny turns in our general
      neurology clinics, but most of us will encounter them. We all pride ourselves on
      a methodical approach to clinical problems-discovering the where and what in
      neurological parlance-but any diagnostic process can unravel, particularly if one
      condition resembles another. Before we settle on a diagnosis, we need to ask
      ourselves, whether the 'ducks all line up' to avoid cases of mistaken identity. 

PMID- 24928574
TI  - Parent changes in diet, physical activity, and behavior in family-based treatment
      for childhood obesity.

PMID- 24928575
TI  - Sexual media exposure, sexual behavior, and sexual violence victimization in
      adolescence.
AB  - BACKGROUND: Emerging research suggests sexual media affects sexual behavior, but
      most studies are based on regional samples and few include measures of newer
      mediums. Furthermore, little is known about how sexual media relates to sexual
      violence victimization. METHODS: Data are from 1058 youth 14 to 21 years of age
      in the national, online Growing up with Media study. RESULTS: Forty-seven percent
      reported that many or almost all/all of at least one type of media they consumed
      depicted sexual situations. Exposure to sexual media in television and movies,
      and music was greater than online and in games. All other things equal, more
      frequent exposure to sexual media was related to ever having had sex, coercive
      sex victimization, and attempted/completed rape but not risky sexual behavior.
      CONCLUSIONS: Longer standing mediums such as television and movies appear to be
      associated with greater amounts of sexual media consumption than newer ones, such
      as the Internet. A nuanced view of how sexual media content may and may not be
      affecting today's youth is needed.

PMID- 24928576
TI  - Trainee and program director perceptions of quality improvement and patient
      safety education: preparing for the next accreditation system.
AB  - OBJECTIVE: To assess the current state of quality improvement and patient safety
      (QIPS) education at a large teaching hospital. METHODS: We surveyed 429 trainees
      (138 residents, 291 clinical fellows) and 38 program directors (PDs; 2 were PDs
      of >1 program) from 39 Accreditation Council for Graduate Medical Education
      accredited training programs. RESULTS: Twenty-nine PDs (76.3%) and 259 trainees
      (60.3%) responded. Most trainees (68.8%) reported participation in projects
      culminating in scholarly products (39.9%) or clinical innovations (44%). Most PDs
      reported that teaching (88.9%) and project supervision (83.3%) are performed by
      expert faculty. Nearly half of the PDs (45.8%) and trainees (49.6%) perceived
      project-based learning to be of equal value to formal curricula. Compared with
      trainees, a greater proportion of PDs reported needs for funding for projects,
      teaching faculty to provide mentorship, and faculty development (P < .05).
      CONCLUSIONS: Providing additional financial, administrative, and operational
      support could enhance the value of curricula and projects. Developing expert
      teaching faculty is paramount.

PMID- 24928577
TI  - Reply to the editor-Can we isolate the pulmonary veins?

PMID- 24928578
TI  - Isolation of the pulmonary veins.

PMID- 24928580
TI  - The mechanism of binding of the second PDZ domain from the Protein Tyrosine
      Phosphatase-BL to the Adenomatous Polyposis Coli tumor suppressor.
AB  - Many biological processes are regulated by the interaction between protein
      domains and their corresponding binding partners. The PDZ domain is one of the
      most common protein-protein interaction modules in mammalian cells, whose role is
      to bind C-terminal sequences of specific targets. The second PDZ domain from the
      Protein Tyrosine Phosphatase-BL (PDZ2) binds to the C-terminal of Adenomatous
      Polyposis Coli protein (APC), one of the major tumor suppressor whose task is to
      regulate cell adhesion and proliferation. Here, we present a detailed kinetics
      analysis of the interaction between PDZ2 domain and a peptide mimicking the PDZ
      binding motif of APC. By analyzing data obtained at different experimental
      conditions, we propose a plausible mechanism for binding. Furthermore, a
      comparison between the dissociation rate constant measured by different
      methodologies allow us to identify an additional kinetic step, which is likely to
      arise from a conformational change of PDZ2 occurring after binding. The data are
      discussed on the light of previous work on PDZ domains. 

PMID- 24928579
TI  - High-risk human papillomavirus in HIV-infected women undergoing cervical cancer
      screening in Lilongwe, Malawi: a pilot study.
AB  - Rates of abnormal visual inspection with acetic acid and prevalence of high-risk
      human papillomavirus (HPV) subtypes have not been well characterized in HIV
      infected women in Malawi. We performed a prospective cohort study of visual
      inspection with acetic acid (N = 440) in HIV-infected women aged 25--59 years,
      with a nested study of HPV subtypes in first 300 women enrolled. Of 440 women
      screened, 9.5% (N = 42) had abnormal visual inspection with acetic acid with
      69.0% (N = 29) having advanced disease not amenable to cryotherapy. Of 294 women
      with HPV results, 39% (N = 114) of women were positive for high-risk HPV
      infection. Only lower CD4 count (287 cells/mm(3) versus 339 cells/mm(3), p =
      0.03) and high-risk HPV (66.7% versus 35.6%, p < 0.01) were associated with
      abnormal visual inspection with acetic acid. The most common high-risk HPV
      subtypes in women with abnormal visual inspection with acetic acid were 35
      (33.3%), 16 (26.7%), and 58 (23.3%). Low CD4 cell count was associated with
      abnormal visual inspection with acetic acid and raises the importance of early
      antiretroviral therapy and expanded availability of visual inspection with acetic
      acid. HPV vaccines targeting additional non-16/18 high-risk HPV subtypes may have
      greater protective advantages in countries such as Malawi. 

PMID- 24928581
TI  - ADAR1: a promising new biomarker for esophageal squamous cell carcinoma?
AB  - Esophageal Squamous Cell Carcinoma (ESCC) is a heterogeneous tumor with enormous
      genetic and epigenetic changes. RNA editing is an epigenetic mechanism that
      serves as an additional layer of 'RNA mutations' in parallel to DNA mutations.
      The most frequent type of RNA editing, A-to-I (adenosine-to-inosine) editing
      catalyzed by Adenosine DeAminase that act on RNA (ADARs), modulates RNA
      transcripts with profound impact on cellular functions. RNA editing dysregulation
      has been found to be associated with cancers. Our recent study demonstrated that
      among all the three RNA editing enzymes, only ADAR1 was overexpressed in primary
      ESCCs compared with matched non-tumor specimens. In this review, we will discuss
      current views on the involvement of abnormal A-to-I editing in cancer
      development, more specifically on the ADAR1-mediated editing in ESCC. Although
      much is not yet learned about the role of ADAR1 in ESCC, ADAR1 may present an
      attractive option as a new biomarker for ESCC and as a new molecular therapeutic
      target. 

PMID- 24928583
TI  - Parents' perspectives on the value of assistance dogs for children with autism
      spectrum disorder: a cross-sectional study.
AB  - OBJECTIVE: While there is an emerging literature on the usefulness of assistance
      dogs for children with autism spectrum disorder (ASD), there is a dearth of
      quantitative data on the value of assistance dog interventions for the family
      unit and family functioning. Using previously validated scales and scales
      developed specifically for this study, we measured parents'/guardians'
      perceptions of how having an assistance dog affects: (1) child safety from
      environmental dangers, (2) public reception of ASD and (3) levels of caregiver
      strain and sense of competence. We also obtained open-ended response data from
      parents/guardians on benefits and constraints of having an assistance dog.
      SETTING: This study was based in the primary care setting, within the context of
      a specific accredited assistance dog centre in Ireland. PARTICIPANTS: A total of
      134 parents/guardians with an assistance dog, and 87 parents of children on the
      waiting list were surveyed. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary
      outcome measures were scores on environmental hazards and public reception
      scales. The secondary outcome measures were scores on caregiver strain and
      competence scales. RESULTS: Parents/guardians of children who have ASD and an
      assistance dog rate their child as significantly safer from environmental dangers
      (p<0.001), perceive that the public act more respectfully and responsibly towards
      their child (p<0.001) and feel more competent about managing their child
      (p=0.023) compared with parents on the waiting list. There was a concentration of
      positive feeling towards assistance dog interventions with particular focus on
      safety and comfort for children, and a sense of freedom from family restrictions
      associated with ASD. The amount of dedication and commitment required to care for
      a dog were viewed as the primary constraints. CONCLUSIONS: Our findings indicate
      that parents perceive that assistance dog interventions can be a valuable
      intervention for families with children who have ASD.

PMID- 24928582
TI  - Differentiation state-specific mitochondrial dynamic regulatory networks are
      revealed by global transcriptional analysis of the developing chicken lens.
AB  - The mature eye lens contains a surface layer of epithelial cells called the lens
      epithelium that requires a functional mitochondrial population to maintain the
      homeostasis and transparency of the entire lens. The lens epithelium overlies a
      core of terminally differentiated fiber cells that must degrade their
      mitochondria to achieve lens transparency. These distinct mitochondrial
      populations make the lens a useful model system to identify those genes that
      regulate the balance between mitochondrial homeostasis and elimination. Here we
      used an RNA sequencing and bioinformatics approach to identify the transcript
      levels of all genes expressed by distinct regions of the lens epithelium and
      maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis
      detected more than 15,000 unique transcripts expressed by the embryonic chicken
      lens. Of these, more than 3000 transcripts exhibited significant differences in
      expression between lens epithelial cells and fiber cells. Multiple transcripts
      coding for separate mitochondrial homeostatic and degradation mechanisms were
      identified to exhibit preferred patterns of expression in lens epithelial cells
      that require mitochondria relative to lens fiber cells that require mitochondrial
      elimination. These included differences in the expression levels of metabolic
      (DUT, PDK1, SNPH), autophagy (ATG3, ATG4B, BECN1, FYCO1, WIPI1), and mitophagy
      (BNIP3L/NIX, BNIP3, PARK2, p62/SQSTM1) transcripts between lens epithelial cells
      and lens fiber cells. These data provide a comprehensive window into all genes
      transcribed by the lens and those mitochondrial regulatory and degradation
      pathways that function to maintain mitochondrial populations in the lens
      epithelium and to eliminate mitochondria in maturing lens fiber cells. 

PMID- 24928584
TI  - How does morphology impact on diastolic function in hypertrophic cardiomyopathy?
      A single centre experience.
AB  - OBJECTIVES: It is unclear if morphology impacts on diastole in hypertrophic
      cardiomyopathy (HCM). We sought to determine the relationship between various
      parameters of diastolic function and morphology in a large HCM cohort. SETTING:
      Tertiary referral centre from Stanford, California, USA. PARTECIPANTS: 383
      patients with HCM and normal systolic function between 1999 and 2011. A group of
      100 prospectively recruited age-matched and sex-matched healthy participants were
      used as controls. PRIMARY AND SECONDARY OUTCOME MEASURES: Echocardiograms were
      assessed by two blinded board-certified cardiologists. HCM morphology was
      classified as described in the literature (reverse, sigmoid, symmetric, apical
      and undefined). RESULTS: Reverse curvature morphology was most commonly observed
      (218 (57%). Lateral mitral annular E'<12 cm/s was present in 86% of reverse, 88%
      of sigmoid, 79% of symmetric, 86% of apical and 81% of undefined morphology,
      p=0.65. E/E' was similarly elevated (E/E': 12.3+/-7.9 in reverse curvature,
      12.1+/-6.1 in sigmoid, 12.7+/-9.5 in symmetric, 9.4+/-4.0 in apical, 12.7+/-7.9
      in undefined morphology, p=0.71) and indexed left atrial volume (LAVi)>40 mL/m(2)
      was present in 47% in reverse curvature, 33% in sigmoid, 32% in symmetric, 37% in
      apical and 32% in undefined, p=0.09. Each morphology showed altered parameters of
      diastolic function when compared with the control population. Left ventricular
      (LV) obstruction was independently associated with all three diastolic parameters
      considered, in particular with LAVi>40 mL/m(2) (OR 2.04 (95% CI 1.23 to 3.39),
      p=0.005), E/E'>15 (OR 4.66 (95% CI 2.51 to 8.64), p<0.001) and E'<8 (OR 2.55 (95%
      CI 1.42 to 4.53), p=0.001). Other correlates of diastolic dysfunction were age,
      LV wall thickness and moderate-to-severe mitral regurgitation. CONCLUSIONS: In
      HCM, diastolic dysfunction is present to similar degrees independently from the
      morphological pattern. The main correlates of diastolic dysfunction are LV
      obstruction, age, degree of hypertrophy and degree of mitral regurgitation.

PMID- 24928585
TI  - Managing risk in cancer presentation, detection and referral: a qualitative study
      of primary care staff views.
AB  - OBJECTIVES: In the UK, there have been a number of national initiatives to
      promote earlier detection and prompt referral of patients presenting to primary
      care with signs and symptoms of cancer. The aim of the study was to explore the
      experiences of a range of primary care staff in promoting earlier presentation,
      detection and referral of patients with symptoms suggestive of cancer. SETTING:
      Six primary care practices in northwest England. PARTICIPANTS: 39 primary care
      staff from a variety of disciplines took part in five group and four individual
      interviews. RESULTS: The global theme to emerge from the interviews was 'managing
      risk', which had three underpinning organising themes: 'complexity', relating to
      uncertainty of cancer diagnoses, service fragmentation and plethora of
      guidelines; 'continuity', relating to relationships between practice staff and
      their patients and between primary and secondary care; 'conflict' relating to
      policy drivers and staff role boundaries. A key concern of staff was that
      policymakers and those implementing cancer initiatives did not fully understand
      how risk was managed within primary care. CONCLUSIONS: Primary care staff
      expressed a range of views and opinions on the benefits of cancer initiatives.
      National initiatives did not appear to wholly resolve issues in managing risk for
      all practitioners. Staff were concerned about the number of guidelines and
      priorities they were expected to implement. These issues need to be considered by
      policymakers when developing and implementing new initiatives.

PMID- 24928586
TI  - Dietary changes and associations with metabolic improvements in adults with type
      2 diabetes during a patient-centred dietary intervention: an exploratory
      analysis.
AB  - OBJECTIVES: Describe dietary intake of participants enrolled in a non
      prescriptive dietary intervention and dietary changes at 6 months and explore
      whether these changes had a role in observed improvements in glycated haemoglobin
      (HbA1c), weight, lipids and blood pressure. DESIGN: Secondary analysis of data
      from the Early ACTivity in Diabetes randomised controlled trial. PARTICIPANTS:
      262 patients with newly diagnosed type 2 diabetes randomised to the dietary
      intervention. OUTCOMES AND ANALYSIS: Changes in energy intake, macronutrients,
      fibre and alcohol and in weight, waist circumference, lipids, HbA1c and blood
      pressure at baseline and 6 months. Multivariate models were used to examine
      associations between dietary changes and metabolic variables. RESULTS: Men
      reported reducing mean energy intake from 1903+/-462 kcal to 1685 kcal+/-439 kcal
      (p<0.001), increasing carbohydrate intake from 42.4+/-6.6% to 43.8+/-6.6%
      (p=0.002) and reducing median alcohol intake from 13 (0-27) g to 5 (0-18) g
      (p<0.001). Women reported reducing mean energy intake from 1582+/-379 kcal to
      1459+/-326 kcal (p<0.001) with no change to macronutrient distribution and
      alcohol. Fibre intake was maintained. In men (n=148), weak and clinically
      insignificant associations were found between increased carbohydrates and
      reduction in HbA1c (beta=-0.003 (-0.006, -0.001); p=0.009), increased fibre and
      reduction in total cholesterol (beta=-0.023 (-0.044, -0.002); p=0.033), decreased
      total fat and reduction in low-density lipoprotein (LDL)-cholesterol (beta=0.024
      (0.006, 0.001); p=0.011), and decreased alcohol and reduction in diastolic blood
      pressure (beta=0.276 (0.055, 0.497); p=0.015). In women (n=75), associations were
      found between a decrease in transfats and reductions in waist circumference
      (beta=-0.029 (0.006, 0.052); p=0.015), total cholesterol (beta=0.399 (0.028,
      0.770); p=0.036) and LDL cholesterol (beta=0.365 (0.042, 0.668); p=0.028).
      CONCLUSIONS: Clinically important metabolic improvements observed in a patient
      centred dietary intervention were not explained by changes in macronutrients.
      However, a non-prescriptive approach may promote a reduction in total energy
      intake while maintaining fibre consumption. TRIAL REGISTRATION NUMBER: The Early
      ACTID trial number ISRCTN92162869.

PMID- 24928587
TI  - Acupuncture as analgesia for non-emergent acute non-specific neck pain, ankle
      sprain and primary headache in an emergency department setting: a protocol for a
      parallel group, randomised, controlled pilot trial.
AB  - INTRODUCTION: This study aims to assess the feasibility of acupuncture as an add
      on intervention for patients with non-emergent acute musculoskeletal pain and
      primary headache in an emergency department (ED) setting. METHODS AND ANALYSIS: A
      total of 40 patients who present to the ED and are diagnosed to have acute non
      specific neck pain, ankle sprain or primary headache will be recruited by ED
      physicians. An intravenous or intramuscular injection of analgesics will be
      provided as the initial standard pain control intervention for all patients.
      Patients who still have moderate to severe pain after the 30 min of initial
      standard ED management will be considered eligible. These patients will be
      allocated in equal proportions to acupuncture plus standard ED management or to
      standard ED management alone based on computer-generated random numbers concealed
      in opaque, sealed, sequentially numbered envelopes. A 30 min session of
      acupuncture treatment with manual and/or electrical stimulation will be provided
      by qualified Korean medicine doctors. All patients will receive additional ED
      management at the ED physician's discretion and based on each patient's response
      to the allocated intervention. The primary outcome will be pain reduction
      measured at discharge from the ED by an unblinded assessor. Adverse events in
      both groups will be documented. Other outcomes will include the patient-reported
      overall improvement, disability due to neck pain (only for neck-pain patients),
      the treatment response rate, the use of other healthcare resources and the
      patients' perceived effectiveness of the acupuncture treatment. A follow-up
      telephone interview will be conducted by a blinded assessor 72+/-12 h after ED
      discharge. ETHICS AND DISSEMINATION: Written informed consent will be obtained
      from all participants. The study has been approved by the Institutional Review
      Boards (IRBs). The results of this study will guide a full-scale randomised trial
      of acupuncture in an ED context. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov:
      NCT02013908.

PMID- 24928588
TI  - Insurance claims data: a possible solution for a national sports injury
      surveillance system? An evaluation of data information against ASIDD and
      consensus statements on sports injury surveillance.
AB  - BACKGROUND: Before preventive actions can be suggested for sports injuries at the
      national level, a solid surveillance system is required in order to study their
      epidemiology, risk factors and mechanisms. There are guidelines for sports injury
      data collection and classifications in the literature for that purpose. In
      Sweden, 90% of all athletes (57/70 sports federations) are insured with the same
      insurance company and data from their database could be a foundation for studies
      on acute sports injuries at the national level. OBJECTIVE: To evaluate the
      usefulness of sports injury insurance claims data in sports injury surveillance
      at the national level. METHOD: A database with 27 947 injuries was exported to an
      Excel file. Access to the corresponding text files was also obtained. Data were
      reviewed on available information, missing information and dropouts. Comparison
      with ASIDD (Australian Sports Injury Data Dictionary) and existing consensus
      statements in the literature (football (soccer), rugby union, tennis, cricket and
      thoroughbred horse racing) was performed in a structured manner. RESULT:
      Comparison with ASIDD showed that 93% of the suggested data items were present in
      the database to at least some extent. Compliance with the consensus statements
      was generally high (13/18). Almost all claims (83%) contained text information
      concerning the injury. CONCLUSIONS: Relatively high-quality sports injury data
      can be obtained from a specific insurance company at the national level in
      Sweden. The database has the potential to be a solid base for research on acute
      sports injuries in different sports at the national level.

PMID- 24928590
TI  - A population-based cross-sectional study of barriers to uptake of eye care
      services in South India: the Rapid Assessment of Visual Impairment (RAVI)
      project.
AB  - OBJECTIVE: To assess the barriers to uptake of eye care services among those with
      avoidable impairment in the population aged >=40 years in the South Indian state
      of Andhra Pradesh. DESIGN: Cross-sectional study. SETTING: Community setting.
      PARTICIPANTS: Of 7800 participants recruited from one urban and two rural
      locations using a two-stage cluster random sampling methodology, 7378 (95%) were
      examined. Eye examinations were conducted using a rapid assessment protocol.
      Visual impairment (VI) was defined as presenting visual acuity <6/18 in the
      better eye. For the purpose of this study, VI caused due to cataract or
      uncorrected refractive error was considered avoidable VI. A validated
      questionnaire was used to collect information on barriers for uptake of services
      among those who had avoidable VI. PRIMARY OUTCOME: Barriers to uptake of services
      among those with avoidable VI. RESULTS: The prevalence of avoidable VI was 11.8%
      (95% CI 11.0% to 12.5%; n=868). Among these, 71.1% (n=617) individuals reported
      'person-related' barriers whereas 28.9% (n=251) individuals reported 'service
      related' barriers to uptake of services. Among the 'person-related' barriers, the
      leading barrier was 'lack of perceived need' (61.1%; n=377) for reasons such as
      old age, good vision in the other eye. This was followed by 'no one to accompany'
      (20.3%; n=125). Of the 251 individuals who had 'service-related' barriers, lack
      of affordability was the major barrier (76.1%; n=191) followed by lack of
      accessibility (12.7%; n=32). Over 11% (n=28) of the individuals were advised to
      wait for cataract surgery. CONCLUSIONS: Person-related barriers are more common
      than service-related barriers in Andhra Pradesh. As the barriers trend more
      towards 'person-related' phenomenon such as person's attitude and 'felt need' to
      improve vision, newer and much intensive awareness campaigns are needed to bring
      about an attitudinal/behavioural change among individuals to improve the uptake
      of services.

PMID- 24928589
TI  - Clinical characteristics and short-term outcomes in patients with elevated
      admission systolic blood pressure after acute ST-elevation myocardial infarction:
      a population-based study.
AB  - OBJECTIVE: Prognostic value of lower admission systolic blood pressure (SBP) in
      patients with acute myocardial infarction has been confirmed, but the impact of
      elevated admission SBP on short-term outcomes has been evaluated only by a
      limited number of studies and they have reported conflicting results. The aim of
      our study was to investigate the characteristics and short-term outcomes in
      patients with elevated admission SBP after ST-elevation myocardial infarction
      (STEMI). DESIGN: A population-based, observational study. SETTING: The
      multicentre registry in China. PARTICIPANTS: A total of 7510 consecutive patients
      with STEMI were registered. Patients were divided into three groups according to
      admission SBP: normal admission SBP (100-139 mm Hg), modestly elevated admission
      SBP (140-179 mm Hg) and excessively elevated admission SBP (>=180 mm Hg). The
      primary outcomes were 7-day and 30-day all-cause mortality, major adverse cardiac
      events (MACE) and bleeding rate. RESULTS: Of 6591 patients, 4182 (63.5%) had
      normal admission SBP, 2187 (33.2%) modestly elevated admission SBP and 222 (3.4%)
      excessively elevated admission SBP. Patients with elevated admission SBP had a
      high-risk profile, such as were more likely to be older, with more concomitant
      cardiovascular morbidities, presenting with more events of anterior myocardial
      infarction and less reperfusion treatment. However, 7-day and 30-day all-cause
      mortality, MACE and bleeding rate were comparable among groups (all p>0.05).
      Survival curves and MACE curves were similar among groups (p=0.377 and 0.375,
      respectively). After multivariate adjustment, elevated admission SBP was not
      associated with increased risk of short-term death and bleeding, and MACE was
      comparable with normal admission SBP. CONCLUSIONS: Although those with elevated
      admission SBP after STEMI were at a higher risk for cardiovascular events, they
      did not have poorer short-term outcomes compared with patients with normal
      admission SBP.

PMID- 24928591
TI  - Long-term clinical outcomes after deployment of femoral vascular closure devices
      in coronary angiography and percutaneous coronary intervention: an observational
      single-centre registry follow-up.
AB  - OBJECTIVES: There are few data evaluating the long-term effect of femoral
      vascular closure devices (FCDs) on patients' clinical outcome. We aim to evaluate
      the incidence of peripheral vascular disease (PVD) in patients who received FCD
      following its deployment in coronary angiography and percutaneous coronary
      intervention (PCI) procedures. DESIGN AND SETTING: Observational study of a
      single-centre registry. PARTICIPANTS: From June 2000 to September 2004, 265
      patients who received FCD after coronary angiography and PCIs were enrolled on
      the study. OUTCOME MEASURES: Clinical follow-up (using Rutherford's categories of
      claudication), ankle brachial index (ABI) and duplex ultrasound of femoral
      arteries (using the non-accessed side as control) were performed to evaluate the
      presence of PVD. RESULTS: The mean follow-up interval was 3320+/-628 days. 1
      patient (0.4%) suffered from grade 2 claudication and another (0.4%) suffered
      from grade 1 claudication. The mean ABIs of the accessed side and non-accessed
      side were 1.06+/-0.13 and 1.08+/-0.11, respectively (p=0.17). For duplex
      ultrasound, the mean common femoral artery peak systolic velocities of the
      accessed side and non-accessed side were 87.4+/-22.3 and 87.7+/-22.1 cm/s,
      respectively (p=0.73); the mean superficial femoral artery peak systolic
      velocities of the accessed side and non-accessed side were 81.4+/-20.1 and
      81.31+/-17.8 cm/s, respectively (p=0.19). CONCLUSIONS: The use of FCD after a
      coronary angiogram and PCI is safe and does not increase the long-term risk of
      PVD.

PMID- 24928592
TI  - Passive smoking at home is a risk factor for community-acquired pneumonia in
      older adults: a population-based case-control study.
AB  - OBJECTIVE: To assess whether passive smoking exposure at home is a risk factor
      for community-acquired pneumonia (CAP) in adults. SETTING: A population-based
      case-control study was designed in a Mediterranean area with 860 000 inhabitants
      >14 years of age. PARTICIPANTS: 1003 participants who had never smoked were
      recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk factors for CAP,
      including home exposure to passive smoking, were registered. All new cases of CAP
      in a well-defined population were consecutively recruited during a 12-month
      period. METHODS: A population-based case-control study was designed to assess
      risk factors for CAP, including home exposure to passive smoking. All new cases
      of CAP in a well-defined population were consecutively recruited during a 12
      month period. The subgroup of never smokers was selected for the present
      analysis. RESULTS: The study sample included 471 patients with CAP and 532
      controls who had never smoked. The annual incidence of CAP was estimated to be
      1.14 cases*10(-3) inhabitants in passive smokers and 0.90*10(-3) in non-passive
      smokers (risk ratio (RR) 1.26; 95% CI 1.02 to 1.55) in the whole sample. In
      participants >=65 years of age, this incidence was 2.50*10(-3) in passive smokers
      and 1.69*10(-3) in non-passive smokers (RR 1.48, 95% CI 1.08 to 2.03). In this
      last age group, the percentage of passive smokers in cases and controls was 26%
      and 18.1%, respectively (p=0.039), with a crude OR of 1.59 (95% CI 1.02 to 2.38)
      and an adjusted (by age and sex) OR of 1.56 (95% CI 1.00 to 2.45). CONCLUSIONS:
      Passive smoking at home is a risk factor for CAP in older adults (65 years or
      more).

PMID- 24928593
TI  - Effect of a redesigned fracture management pathway and 'virtual' fracture clinic
      on ED performance.
AB  - OBJECTIVES: Collaboration between the orthopaedic and emergency medicine (ED)
      services has resulted in standardised treatment pathways, leaflet supported
      discharge and a virtual fracture clinic review. Patients with minor, stable
      fractures are discharged with no further follow-up arranged. We aimed to examine
      the time taken to assess and treat these patients in the ED along with the rate
      of unplanned reattendance. DESIGN: A retrospective study was undertaken that
      covered 1 year before the change and 1 year after. Prospectively collected
      administrative data from the electronic patient record system were analysed and
      compared before and after the change. SETTING: An ED and orthopaedic unit,
      serving a population of 300 000, in a publicly funded health system.
      PARTICIPANTS: 2840 patients treated with referral to a traditional fracture
      clinic and 3374 patients managed according to the newly redesigned protocol.
      OUTCOME MEASURES: Time for assessment and treatment of patients with orthopaedic
      injuries not requiring immediate operative management, and 7-day unplanned
      reattendance. RESULTS: Where plaster backslabs were replaced with removable
      splints, the consultation time was reduced. There was no change in treatment time
      for other injuries treated by the new discharge protocol. There was no increase
      in unplanned ED attendance, related to the injury, within 7 days (p=0.149). There
      was a decrease in patients reattending the ED due to a missed fracture clinic
      appointment. CONCLUSIONS: This process did not require any new time resources
      from the ED staff. This process brought significant benefits to the ED as
      treatment pathways were agreed. The pathway reduced unnecessary reattendance of
      patients at face-to-face fracture clinics for a review of stable, self-limiting
      injuries.

PMID- 24928594
TI  - Effect of exercise on anthropometric measures and serum lipids in older
      individuals: a systematic review and meta-analysis.
AB  - OBJECTIVES: Overweight and obesity are increasing in individuals over age 60
      years. This systematic review quantifies the effect of exercise on body mass
      index (BMI), waist circumference (WC) and lipids in overweight and obese
      individuals over the age of 60 years. SETTINGS: Nine randomised controlled trials
      conducted in Brazil, Great Britain, Iceland, Japan and the USA compared aerobic
      and/or resistance exercise with a control group. PARTICIPANTS: Final analysis
      reviewed 1166 participants over the age of 60 years for 3-9 months. PRIMARY
      OUTCOME MEASURES: This study reviewed the effects of exercise on BMI, WC and low
      density lipoprotein (LDL). RESULTS: Exercise produced a significant reduction in
      BMI (-1.01 kg/m(2), 95% CI -2.00 to -0.01) and WC (-3.09 cm, 95% CI -4.14 to 
      2.04) but not LDL cholesterol (-0.31 mg/dL, 95% CI -0.81 to 0.19). Analyses
      revealed substantial heterogeneity likely due to the type and intensity of
      exercise. Data on adverse effects were minimal. The overall level of evidence is
      moderate due to imprecision and heterogeneity. CONCLUSIONS: Exercise in
      overweight and obese older individuals improves anthropometric measures such as
      BMI and WC. The effect of exercise on serum lipids is unclear.

PMID- 24928596
TI  - How common are symptoms? Evidence from a New Zealand national telephone survey.
AB  - OBJECTIVE: To assess the frequency of symptoms in a general population sample
      over the previous week and the associations between symptom reporting and
      demographic factors, medical visits and medication use. DESIGN: A representative
      general population sample (n=1000) was recruited using random digit dialling.
      Participants were asked whether they had experienced any of a list of 46 symptoms
      in the previous 7 days and if so, whether the symptom was mild, moderate or
      severe. Demographic data and information on medical visits and medication use
      were also collected. RESULTS: Symptom reporting was very common. The median
      number of symptoms reported by participants in the previous week was 5 with only
      10.6% of participants reporting no symptoms. The five most common symptoms in the
      previous 7 days were: back pain (38%), fatigue (36%), headache (35%), runny or
      stuffy nose (34%) and joint pain (34%). The five symptoms rated highest in terms
      of severity were sexual difficulties, vomiting, tremor, suicidal thoughts and
      sleep problems. Symptom reporting was significantly positively associated with
      medical visits in the previous year and current medication taking. Women reported
      a significantly greater number of symptoms. We found no significant association
      between age or household size and symptom reporting. CONCLUSIONS: This population
      based study found that symptoms are more commonly experienced in the general
      population than previously estimated and are strongly associated with healthcare
      visits. Appreciation of the high prevalence of symptoms may help normalise the
      experience of symptom reports among the general population.

PMID- 24928595
TI  - A hard pill to swallow: a qualitative study of women's experiences of adjuvant
      endocrine therapy for breast cancer.
AB  - OBJECTIVE: To explore women's experiences of taking adjuvant endocrine therapy as
      a treatment for breast cancer and how their beliefs about the purpose of the
      medication, side effects experienced and interactions with health professionals
      might influence adherence. DESIGN: Qualitative study using semistructured, one-to
      one interviews. SETTING: 2 hospitals from a single health board in Scotland.
      PARTICIPANTS: 30 women who had been prescribed tamoxifen or aromatase inhibitors
      (anastrozole or letrozole) and had been taking this medication for 1-5 years.
      RESULTS: Women clearly wished to take their adjuvant endocrine therapy medication
      as prescribed, believing that it offered them protection against breast cancer
      recurrence. However, some women missed tablets and did not recognise that this
      could reduce the efficacy of the treatment. Women did not perceive that
      healthcare professionals were routinely or systematically monitoring their
      adherence. Side effects were common and impacted greatly on the women's quality
      of life but did not always cause women to stop taking their medication, or to
      seek advice about reducing the side effects they experienced. Few were offered
      the opportunity to discuss the impact of side effects or the potential options
      available. CONCLUSIONS: Although most women in this study took adjuvant endocrine
      therapy as prescribed, many endured a range of side effects, often without
      seeking help. Advice, support and monitoring for adherence are not routinely
      offered in conventional follow-up settings. Women deserve more opportunity to
      discuss the pros, cons and impact of long-term adjuvant endocrine therapy. New
      service models are needed to support adherence, enhance quality of life and
      ultimately improve survival. These should ideally be community based, in order to
      promote self-management in the longer term.

PMID- 24928597
TI  - Maternal urinary iodine concentration in pregnancy and children's cognition:
      results from a population-based birth cohort in an iodine-sufficient area.
AB  - OBJECTIVE: Reports from populations with an insufficient iodine intake suggest
      that children of mothers with mild iodine deficiency during pregnancy are at risk
      for cognitive impairments. However, it is unknown whether, even in iodine
      sufficient areas, low levels of iodine intake occur that influence cognitive
      development in the offspring. This study investigated the association between
      maternal low urinary iodine concentration (UIC) in pregnancy and children's
      cognition in a population-based sample from a country with an optimal iodine
      status (the Netherlands). SETTING AND PARTICIPANTS: In 1525 mother-child pairs in
      a Dutch multiethnic birth cohort, we investigated the relation between maternal
      UIC<150 MUg/g creatinine, assessed <18 weeks gestation and children's cognition.
      OUTCOMES MEASURES: Non-verbal IQ and language comprehension were assessed during
      a visit to the research centre using Dutch test batteries when the children were
      6 years. RESULTS: In total, 188 (12.3%) pregnant women had UIC<150 MUg/g
      creatinine, with a median UIC equal to 119.3 MUg/g creatinine. The median UIC in
      the group with UIC>150 MUg/g creatinine was 322.9 MUg/g and in the whole sample
      296.5 MUg/g creatinine. There was a univariate association between maternal low
      UIC and children's suboptimum non-verbal IQ (unadjusted OR=1.44, 95% CI 1.02 to
      2.02). However, after adjustment for confounders, maternal low UIC was not
      associated with children's non-verbal IQ (adjusted OR=1.33, 95% CI 0.92 to 1.93).
      There was no relation between maternal UIC in early pregnancy and children's
      language comprehension at 6 years. CONCLUSIONS: The lack of a clear association
      between maternal low UIC and children's cognition probably reflects that low
      levels of iodine were not frequent and severe enough to affect neurodevelopment.
      This may result from the Dutch iodine fortification policy, which allows iodised
      salt to be added to almost all processed food and emphasises the monitoring of
      iodine intake in the population.

PMID- 24928598
TI  - Comparison of two methods for measurement of equine insulin.
AB  - Diagnosis of equine hyperinsulinemia requires an accurate method for
      quantification of equine insulin concentrations. The objectives of the current
      study were to compare 2 commercially available techniques for measurement of
      equine insulin, the radioimmunoassay (RIA) and chemiluminescent immunoassay
      (CIA). Recovery was poor for both assays, but worse for the CIA. Serial dilution
      of a high endogenous insulin sample yielded better linearity for the RIA ( r2 =
      0.99, P < 0.001) than the CIA ( r2 = 0.92, P = 0.009). Bland-Altman analysis
      indicated that the CIA was, on average, 91 pmol/l higher than the RIA, with wide
      limits of agreement (95% limits of agreement: -508 to 691 pmol/l). These findings
      suggest that results between the assays should not be considered interchangeable.

PMID- 24928599
TI  - Detection and genetic characterization of Canine parvovirus and Canine
      coronavirus strains circulating in district of Tirana in Albania.
AB  - An epidemiological survey for Canine parvovirus 2 (CPV-2) and Canine coronavirus
      (CCoV) was conducted in Albania. A total of 57 fecal samples were collected from
      diarrheic dogs in the District of Tirana during 2011-2013. The molecular assays
      detected 53 and 31 CPV- and CCoV-positive specimens, respectively, with mixed CPV
      CCoV infections diagnosed in 28 dogs. The most frequently detected CPV type was
      2a, whereas IIa was the predominant CCoV subtype. A better comprehension of the
      CPV-CCoV epidemiology in eastern European countries will help to assess the most
      appropriate vaccination strategies to prevent disease due to infections with
      these widespread agents of acute gastroenteritis in the dog.

PMID- 24928602
TI  - Foreword.

PMID- 24928603
TI  - The life-cycle argument: age as a mediator of pharmacists' earnings.
AB  - BACKGROUND: Age diversity poses challenges to pharmacy employers and managers. A
      life-cycle argument has been presented to explain pharmacists' age-related
      differences at work. OBJECTIVES: Explore responses of pharmacists' wage-and
      salary earnings in three age groups (younger than 40, 40-54 years, and 55 years
      plus) to labor input and human-capital variables. METHODS: A survey questionnaire
      was mailed to registered pharmacists in South Florida, USA. An earnings function
      was formulated and tested, using ordinary least squares, for each age group
      separately to compare the direction, magnitude, and statistical significance of
      each determinant on earnings. The covariates were number of hours worked, type of
      pharmacy degree, years of professional experience, gender, number of children,
      and whether the pharmacist had completed a residency and/or attained a specialty
      board certification. RESULTS: The model showed better fit and statistical
      significance for practitioners under 40 and 55 years or older. The number of
      hours worked was the overwhelming determinant, but the magnitude of its influence
      was different for the three age groups. Human-capital indicators provided
      evidence in support of the life-cycle argument. CONCLUSION: The wage-and-salary
      earnings of pharmacy practitioners were mediated by age group in their response
      to labor input and human-capital variables.

PMID- 24928605
TI  - Editor's foreword.

PMID- 24928604
TI  - Energy expenditure, spontaneous physical activity and with weight gain in kidney
      transplant recipients.
AB  - BACKGROUND & AIMS: Alterations in energy metabolism could trigger weight gain
      after renal transplantation. METHODS: Nineteen transplanted non-diabetic men, 53
      +/- 1.6 years old, receiving calcineurin inhibitors but no corticosteroids were
      studied. They were compared with nine healthy men matched for height, age and
      lean body mass. Daily energy expenditure and its components (sleeping, basal and
      absorptive metabolic rates) were analyzed for 24 h in calorimetric chambers and
      for 4 days in free living conditions using calibrated accelerometry. Other
      variables known to influence energy expenditure were assessed: body composition,
      physical activity, 4-day food intake, drug consumption, serum C-reactive protein,
      interleukin-6, thyroid and parathyroid hormones, and epinephrine. Transplant
      recipients who gained more than 5% body weight after transplantation (n = 11,
      +11.0 +/- 1.5 kg) were compared with those who did not (n = 8) and with the
      controls. RESULTS: Weight gain compared with non-weight gain patients and
      controls exhibited higher fat mass without change in lean body mass. Daily,
      sleeping and resting energy expenditure adjusted for lean body mass was
      significantly higher in non-weight gain (167.1 +/- 4.2 kJ/kg/lean body mass/24 h,
      P < 0.05) compared with weight gain patients (147.4 +/- 3.6) and controls (146.1
      +/- 4.6). Weight gain compared with controls and non-weight gain subjects had
      lower free living physical activity and a higher consumption of antihypertensive
      drugs and beta-blockers. CONCLUSIONS: After kidney transplantation, weight gain
      patients were characterized by lower adjusted energy expenditure, reduced
      spontaneous physical activity but a more sedentary life style and a trend toward
      a higher energy intake explaining the reason they gained weight. The nWG KTR had
      increased resting and sleeping EE which protected them from weight gain. Such
      hypermetabolism was also observed in 24-h EE measurements. By comparison with the
      nWG patients, the WG transplant recipients were characterized by higher beta
      blocker consumption. These data could be helpful in the prevention of weight gain
      in kidney transplant recipients.

PMID- 24928606
TI  - "When nothing matters, things just happen": young parenting women's reflections
      on caring, health, and justice.
AB  - The field of public health frequently issues calls for social justice, but it is
      not clear that everyone agrees on what this means or how to achieve it. To assess
      lay citizens' views on the relationship between justice and health, we conducted
      individual interviews with 19 young parenting women to hear and discuss their
      thoughts about the causes of health disparities, ways to reduce them, and the
      nature of the just society. A salient theme to emerge in these interviews was the
      topic of "caring." This article reports on four categories identified under the
      theme of caring: 1) observations of apathy and indifference; 2) the effects of
      not caring; 3) models of caring; and 4) the pull of caring. Based on these
      results, the article outlines a grounded theory on the role of caring in
      conceptualizing health motivation. 

PMID- 24928607
TI  - Establishing health ministries: leaders' perceptions of process and
      effectiveness.
AB  - Church-based health interventions are one mechanism to address health issues of
      African Americans. This study determines the perceptions of health leaders
      regarding the development process for and the effectiveness of church health
      ministries, using the Precede/Proceed model. Ten health leaders from six medium
      sized churches in a North Florida county participated in a 10-month breast health
      intervention. Data were collected using two methods. A brief questionnaire was
      administered that included items related to knowledge about breast health,
      perceptions of and processes for health ministry development, and perceptions of
      resources used during the intervention. In addition, a focus group was conducted
      with the health leaders, using a trained moderator, which included questions
      about their health behaviors prior to and after the project, biggest successes
      and challenges in establishing their health ministries, and plans for sustaining
      the health ministry after the project. Questionnaire data were analyzed using
      descriptive statistics and paired t-tests. Focus group data and open-ended
      questionnaire responses were transcribed and analyzed using code-based analytic
      procedures where data were organized into thinking units, categories, and then
      broader themes. Findings indicate that health leaders perceived that health
      ministry development focused on a series of steps, including: a) predisposing:
      health leaders background (personal characteristics, education/profession, health
      behaviors); b) enabling: support and participation from the pastor; and c)
      reinforcing: start-up processes (personal contact, public relations, materials
      and church member involvement) and outputs (activities and partnerships). This
      study demonstrates that health ministry development involves a sequential process
      that fits within a broad organizational framework for health behavior change. 

PMID- 24928608
TI  - Teacher perspectives on implementing and sustaining a handwashing promotion
      intervention in Western Kenyan primary schools.
AB  - School-based handwashing programs are challenging to establish and sustain,
      especially in low-resource settings. This qualitative study described teacher
      perspectives associated with implementing and sustaining a handwashing program in
      primary schools participating in the Nyando Integrated Child Health and Education
      (NICHE) project. Structured key informant interviews were conducted with
      teachers. Prevalent concepts and themes were grouped into themes and topic areas
      using an iterative, open coding approach. Forty-one teacher respondents reported
      favorable expectations and benefits of handwashing programs. The importance of
      available resources (e.g., reliable water) was cited as a primary concern. Other
      challenges included time and personal or institutional financial commitment
      necessary to ensure program sustainability. Handwashing programs in low-income,
      rural schools, where infrastructure is lacking and "student ambassadors" extend
      the intervention to the surrounding community, hold great promise to improve
      community health. Teachers must have adequate support and resources to implement
      and sustain the programs. 

PMID- 24928609
TI  - A community-based intervention to promote breast cancer awareness and screening
      among Asian American women.
AB  - Cancer is the leading cause of death for Asian Americans, and breast cancer is
      the leading cancer diagnosed among Asian American women. Despite the alarming
      facts, Asian American women have low breast cancer screening rates. This study
      examined the effects of a culturally appropriate community-based breast
      intervention program on participants' knowledge about breast cancer and intention
      for screening among Southeast Asian and South Asian women in Michigan. Data were
      collected from 166 women. At baseline, participants had limited knowledge of
      breast cancer screening guidelines and misconceptions about the risk factors of
      breast cancer. After the educational intervention, participants reported
      significantly higher knowledge scores related to breast cancer and screening
      recommendations and intentions to obtain follow-up CBE and mammograms. This
      culturally appropriate intervention provides strategies to overcome personal
      instructional barriers to meet the needs of this group for early detection and
      cancer control. 

PMID- 24928610
TI  - Predicting childhood obesity prevention behaviors using social cognitive theory
      among upper elementary African-American children.
AB  - Childhood obesity is a major public health problem in the African-American
      community. Commonly suggested public health strategies to reduce childhood
      obesity are limiting television viewing, encouraging daily moderately intense
      physical activity of at least 60 minutes per day, increasing fruit and vegetable
      intake to five or more cups per day, and increasing water consumption. This study
      examined the extent to which selected social cognitive theory constructs can
      predict these four behaviors in African-American upper elementary children. A 56
      item valid and reliable scale was administered to 222 students. Glasses of water
      consumed were predicted by self-control for drinking water and self-efficacy for
      drinking water (R2 = 0.123). Fruits and vegetables consumed were predicted by
      self-efficacy for eating fruits and vegetables (R2 = 0.083). For designing
      primary prevention interventions to reduce childhood obesity in the African
      American community, social cognitive theory provides a useful framework. 

PMID- 24928611
TI  - Suburban sprawl in the developing world: duplicating past mistakes? The case of
      Kuala Lumpur, Malaysia.
AB  - Newly affluent developing world cities increasingly adopt the same unfortunate
      low-density suburban paradigm that shaped cities in the industrialized world.
      Identified by a World Bank report as a "mini-Los Angeles," Kuala Lumpur is a
      sentinel example of the results of unrestrained sprawl in the developing world.
      Factors driving sprawl included government policies favoring foreign investment,
      "mega-projects," and domestic automobile production; fragmented governance
      structures allowing federal and state government influence on local planning;
      increasing middle-class affluence; an oligopoly of local developers; and
      haphazard municipal zoning and transport planning. The city's present form
      contributes to Malaysia's dual burden of disease, with inner-city shantytown
      dwellers facing communicable disease and malnutrition while suburban citizens
      experience increasing chronic disease, injury, and mental health issues. Despite
      growing awareness in city plans targeted toward higher density development, Kuala
      Lumpur presents a warning to other emerging economies of the financial, societal,
      and population health costs imposed by quickly-built suburban sprawl. 

PMID- 24928612
TI  - 6-thioguanine: a drug with unrealized potential for cancer therapy.
AB  - Sixty years ago, 6-thioguanine (6-TG) was introduced into the clinic. We suggest
      its full potential in therapy may not have been reached. In this paper, we
      contrast 6-TG and the more widely used 6-mercaptopurine; discuss 6-TG metabolism,
      pharmacokinetics, dosage and schedule; and summarize many of the early studies
      that have shown infrequent but nevertheless positive results with 6-TG treatment
      of cancers. We also consider studies that suggest that combinations of 6-TG with
      other agents may enhance antitumor effects. Although not yet tested in man, 6-TG
      has recently been proposed to treat a wide variety of cancers with a high
      frequency of homozygous deletion of the gene for methylthioadenosine
      phosphorylase (MTAP), often codeleted with the adjacent tumor suppressor CDKN2A
      (p16). Among the cancers with a high frequency of MTAP deficiency are leukemias,
      lymphomas, mesothelioma, melanoma, biliary tract cancer, glioblastoma,
      osteosarcoma, soft tissue sarcoma, neuroendocrine tumors, and lung, pancreatic,
      and squamous cell carcinomas. The method involves pretreatment with the naturally
      occurring nucleoside methylthioadenosine (MTA), the substrate for the enzyme
      MTAP. MTA pretreatment protects normal host tissues, but not MTAP-deficient
      cancers, from 6-TG toxicity and permits administration of doses of 6-TG that are
      much higher than can now be safely administered. The combination of MTA/6-TG has
      produced substantial shrinkage or slowing of growth in two different xenograft
      human tumor models: lymphoblastic leukemia and metastatic prostate carcinoma with
      neuroendocrine features. Further development and a clinical trial of the proposed
      MTA/6-TG treatment of MTAP-deficient cancers seem warranted. 

PMID- 24928613
TI  - The European Medicines Agency Review of Pertuzumab for the treatment of adult
      patients with HER2-positive metastatic or locally recurrent unresectable breast
      cancer: summary of the scientific assessment of the committee for medicinal
      products for human use.
AB  - Pertuzumab is a recombinant humanized monoclonal antibody that specifically
      targets the extracellular dimerization domain (subdomain II) of HER2. Based on
      the positive opinion from the European Medicines Agency (EMA) on March 4, 2013, a
      marketing authorization valid throughout the European Union (EU) was issued for
      pertuzumab (Perjeta) for use in combination with trastuzumab and docetaxel for
      the treatment of adult patients with HER2-positive metastatic or locally
      recurrent unresectable breast cancer who have not received previous anti-HER2
      therapy or chemotherapy for their metastatic disease. The demonstration of
      clinical benefit for pertuzumab was based on a single, phase III, randomized,
      double-blind, placebo-controlled trial comparing the efficacy and safety of
      pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus
      docetaxel in previously untreated patients with locally advanced or metastatic
      HER2-positive breast cancer. In the primary analysis, median progression-free
      survival was 18.5 months in the pertuzumab group compared with 12.4 months in the
      placebo group (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.51-0.75;
      p < .0001). For the secondary endpoints, overall survival (HR: 0.66; 95% CI: 0.52
      0.84; p = .0008) and objective response rate (80.2% vs. 69.3%) were also favored
      in the pertuzumab group. Toxicity was similar between groups except for higher
      incidence of diarrhea, rash, mucosal inflammation, dry skin, and neutropenia for
      pertuzumab compared with placebo. This paper summarizes the scientific review of
      the application leading to approval in the EU. The detailed scientific assessment
      report and product information, including the summary of product characteristics,
      are available on the EMA website (http://www.ema.europa.eu). 

PMID- 24928614
TI  - Cervical brachytherapy exchange: steps toward oncology capacity building in
      Botswana.

PMID- 24928615
TI  - Cognitive dysfunction might be improved in association with recovered neuronal
      viability after intracranial meningioma resection.
AB  - Intracranial meningiomas are the most common types of neoplasms that cause mental
      disorders. Although higher brain function can be restored and even improved in
      some patients after tumor resection, the mechanisms remain unclear. We
      investigated changes in the brains of patients after resection of an intracranial
      meningioma using (123)I-Iomazenil (IMZ)-single photon emission computed
      tomography (SPECT). Ten patients underwent IMZ-SPECT within 4 weeks before and 3
      months after intracranial meningioma resection. Changes in IMZ accumulation in
      brain parenchyma were assessed as ratios of counts in the lesion-to-contralateral
      hemisphere (L/C ratios). Mean Mini-Mental State Examination scores before and
      after resection of 19.9+/-11.4 vs. 26.5+/-3.8, respectively (p=0.03) indicated
      that the cognitive function of these patients was significantly improved after
      tumor resection. The average L/C ratios calculated from image counts of IMZ were
      0.92+/-0.05 and 0.98+/-0.02 before and after surgery, respectively. The L/C ratio
      of IMZ accumulation was significantly decreased after tumor resection (p=0.0003).
      In contrast, regional cerebral blood flow calculated from (123)I-Iodoamphetamine
      SPECT images did not significantly differ after tumor resection. The recovered
      binding potential of IMZ in brain parenchyma surrounding the tumor bulk after
      resection indicates that the viability of central benzodiazepine receptors was
      reversibly depressed and recoverable after release from compression by the tumor.
      The recovered neuronal viability revealed by IMZ-SPECT might be responsible for
      the improved cognitive function after intracranial meningioma resection. 

PMID- 24928616
TI  - Role of medial prefrontal and orbitofrontal monoamine transporters and receptors
      in performance in an adjusting delay discounting procedure.
AB  - Performance in an adjusting delay discounting procedure is predictive of drug
      abuse vulnerability; however, the shared underlying specific prefrontal neural
      systems linking delay discounting and increased addiction-like behaviors are
      unclear. Rats received direct infusions of methylphenidate (MPH; 6.25, 25.0, or
      100MUg), amphetamine (AMPH; 0.25, 1.0, or 4.0MUg), or atomoxetine (ATO; 1.0, 4.0,
      or 16.0MUg) into either medial prefrontal cortex (mPFC) or orbitofrontal cortex
      (OFC) immediately prior to performance in an adjusting delay task. These drugs
      were examined because they are efficacious in treating impulse control disorders.
      Because dopamine (DA) and serotonin (5-HT) receptors are implicated in impulsive
      behavior, separate groups of rats received microinfusions of the DA receptor
      selective drugs SKF 81297 (0.1 or 0.4ug), SCH 23390 (0.25 or 1.0ug), quinpirole
      (1.25 or 5.0ug), and eticlopride (0.25 or 1.0ug), or received microinfusions of
      the 5-HT receptor-selective drugs 8-OH-DPAT (0.025 or 0.1MUg), WAY 100635 (0.01
      or 0.04MUg), DOI (2.5 or 10.0MUg), and ketanserin (0.1 or 0.4MUg). Impulsive
      choice was not altered significantly by MPH, AMPH, or ATO into either mPFC or
      OFC, indicating that neither of these prefrontal regions alone may mediate the
      systemic effect of ADHD medications on impulsive choice. However, quinpriole
      (1.25MUg) and eticlopride infused into mPFC increased impulsive choice, whereas 8
      OH-DPAT infused into OFC decreased impulsive choice. These latter results
      demonstrate that blockade of DA D2 receptors in mPFC or activation of 5-HT1A
      receptors in OFC increases impulsive choice in the adjusting delay procedure. 

PMID- 24928617
TI  - The impact of egocentric vs. allocentric agency attributions on the neural bases
      of reasoning about social rules.
AB  - We used the "standard" and "switched" social contract versions of the Wason
      Selection-task to investigate the neural bases of human reasoning about social
      rules. Both these versions typically elicit the deontically correct answer, i.e.
      the proper identification of the violations of a conditional obligation. Only in
      the standard version of the task, however, this response corresponds to the
      logically correct one. We took advantage of this differential adherence to
      logical vs. deontical accuracy to test the different predictions of logic rule
      based vs. visuospatial accounts of inferential abilities in 14 participants who
      solved the standard and switched versions of the Selection-task during functional
      Magnetic-Resonance-Imaging. Both versions activated the well known left fronto
      parietal network of deductive reasoning. The standard version additionally
      recruited the medial parietal and right inferior parietal cortex, previously
      associated with mental imagery and with the adoption of egocentric vs.
      allocentric spatial reference frames. These results suggest that visuospatial
      processes encoding one's own subjective experience in social interactions may
      support and shape the interpretation of deductive arguments and/or the resulting
      inferences, thus contributing to elicit content effects in human reasoning.

PMID- 24928619
TI  - A comparison of factors involved in the development of central nervous system and
      pulmonary oxygen toxicity in the rat.
AB  - Central nervous system oxygen toxicity (CNS-OT) can occur in humans at pressures
      above 2atmospheres absolute (ATA), and above 4.5ATA in the rat. Pulmonary oxygen
      toxicity appears at pressures above 0.5ATA. We hypothesized that exposure to mild
      HBO following extreme exposure might provide protection against CNS, but not
      pulmonary oxygen toxicity. We measured the activity of superoxide dismutase
      (SOD), catalase (CAT) and glutathione peroxidase (GPX), and nitrotyrosine and
      nNOS levels in the brain and lung in the following groups: (1) Sham rats, no
      pressure exposure (SHAM); (2) Exposure to 6ATA oxygen for 60% of latency to CNS
      OT (60%LT); (3) Exposure to 6ATA for 60% of latency to CNS-OT, followed by 20min
      at 2.5ATA for recovery (REC); (4) Exposure to 6ATA for 60% of latency to CNS-OT,
      followed by 20min at 2.5ATA oxygen and a subsequent increase in pressure to 6ATA
      until the appearance of convulsions (CONV); (5) Control rats exposed to 6ATA
      until the appearance of convulsions (C). SOD and CAT activity were reduced in
      both brain and lung in the REC group. GPX activity was reduced in the hippocampus
      in the REC group, but not in the cortex or the lung. nNOS levels were reduced in
      the hippocampus in the REC group. Contrary to our hypothesis, no difference was
      observed between the brain and the lung for the factors investigated. We suggest
      that at 2.5ATA and above, CNS and pulmonary oxygen toxicity may share similar
      mechanisms. 

PMID- 24928620
TI  - Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat
      model of Parkinson's disease.
AB  - Deferoxamine (DFO) has shown therapeutic promise for the treatment of Parkinson's
      disease (PD) as it has reduced both behavioral and biochemical deficits when
      injected into the brain of rodent models of PD. Intranasally administered DFO
      targets the brain directly but non-invasively and has been effective in animal
      models of stroke and Alzheimer's disease. In this study we sought to determine
      whether intranasal (IN) DFO could be neuroprotective for PD in a rat model. PD
      was induced with a unilateral injection of 6-hydroxydopamine (6-OHDA) into the
      medial forebrain bundle, while sham surgery rats received saline injections. Rats
      were pre-treated three times with either IN DFO or saline (starting 4 days before
      6-OHDA), and post-treated twice/wk for one month before behavioral tests. In the
      apomorphine-induced rotational test, IN DFO significantly decreased the number of
      contralateral turns after injection of apomorphine HCl (p<0.05). Also, IN DFO
      significantly decreased limb asymmetry in the rearing tube as measured with
      contralateral limb touches (p<0.05). The IN DFO treatment yielded a trend towards
      decreased contralateral foot-slips on the tapered balance beam, though the
      difference was not significant. Finally, IN DFO-treated rats had increased
      preservation of tyrosine hydroxylase immunoreactive neurons in the substantia
      nigra (p<0.05). These results confirm that DFO is beneficial in a 6-OHDA model
      and demonstrate improvement in motor deficits and dopaminergic neuronal survival
      with non-invasive intranasal delivery, making this an attractive potential
      treatment for PD. 

PMID- 24928621
TI  - Glycobiology of platelet-endothelial cell interactions.
AB  - Under normal conditions, platelets do not interact with blood vessel walls;
      however, upon activation, platelets firmly attach to endothelial cells.
      Communication between platelets and endothelial cells during the normal or
      activated state takes place at multiple levels. Cross-talk may occur over a
      distance via transient interactions or through receptor-mediated cell-cell
      adhesion. Platelets may release or transfer substances that affect endothelial
      cell function and vice versa. Excessive dialogue between platelets and the
      endothelium exists in several disease states as a causative factor and/or as a
      consequence of the disease process. Glycans are covalent assemblies of sugars
      that exist in either free form or in covalent complexes with proteins or lipids.
      Among other functions, glycans confer stability to the proteins to which they are
      attached, play key roles in signal transduction and control cell development and
      differentiation. Glycans not only influence the structure and function of
      hemostatic molecules but are also increasingly recognized as key molecules
      regulating platelet-endothelial interactions. The present review outlines the
      current knowledge regarding glycan-mediated interactions between platelets and
      endothelial cells and their role in physiopathological processes. 

PMID- 24928622
TI  - [Not Available].

PMID- 24928618
TI  - TLR signaling controls lethal encephalitis in WNV-infected brain.
AB  - Toll-like receptors (TLRs) are known to be activated in Central Nervous System
      (CNS) viral infections and are recognized to be a critical component in innate
      immunity. Several reports state a role for particular TLRs in various CNS viral
      infections. However, excessive TLR activation was previously reported by us in
      correlation with a pathogenic, rather than a protective, outcome, in a model of
      SIV encephalitis. Here we aimed at understanding the impact of TLR-mediated
      pathways by evaluating the early course of pathogenesis in the total absence of
      TLR signaling during CNS viral infections. We utilized a mouse model of sublethal
      West Nile virus (WNV) infection. WNV is an emerging neurotropic flavivirus, and a
      significant global cause of viral encephalitis. The virus was peripherally
      injected into animals that simultaneously lacked two key adapter molecules of TLR
      signaling, MyD88 and TRIF. On day 2 pi (post infection), MyD88/Trif-/- mice
      showed an increased susceptibility to WNV infection, and revealed an impairment
      in innate immune cytokines, when compared to wild type mice (WT). By day 6 pi,
      there was an increase in viral burden and robust expression of inflammatory
      cytokines as well as higher cell infiltration into the CNS in MyD88/Trif-/-, when
      compared to infected WT. A drastic increase in microglia activation,
      astrogliosis, and inflammatory trafficking were also observed on day 6 pi in
      MyD88/Trif-/-. Our observations show a protective role for TLR signaling pathways
      in preventing lethal encephalitis at early stages of WNV infection. 

PMID- 24928623
TI  - [Not Available].

PMID- 24928624
TI  - [Not Available].

PMID- 24928625
TI  - [Not Available].

PMID- 24928626
TI  - [Not Available].

PMID- 24928627
TI  - [Not Available].

PMID- 24928628
TI  - [Not Available].

PMID- 24928629
TI  - Protective effects of chelerythrine against lipopolysaccharide-induced endotoxic
      shock in mice.
AB  - Chelerythrine (CHE), a quaternary benzo[c]phenanthridine alkaloid, exhibits a
      wide spectrum of pharmacological effects. Although CHE has been used to treat
      various diseases, the protective effects of CHE on lipopolysaccharide (LPS)
      induced endotoxic shock have not been explored. The aims of the study were to
      investigate the protective effects of CHE on LPS-induced endotoxic shock in mice
      and clarify the mechanism of the effects. We found that pretreatment with CHE (1,
      5, and 10 mg/kg, po) at 1 and 12 h before injected intraperitoneally with 1 mg/kg
      LPS markedly decreased the production of interleukin-6 (IL-6), tumor necrosis
      factor alpha (TNF-alpha), and myeloperoxidase (MPO) and attenuated the lung
      histopathological changes. Meanwhile, the effects were dependent on the
      inhibition of the expression of p65 nuclear factor kappaB (NF-kappaB). The
      protective effects of CHE on LPS-induced endotoxic shock can be attributed to
      attenuating inflammatory cytokines and inhibition of the expression of NF-kappaB.

PMID- 24928631
TI  - Register now for the residue world cup.

PMID- 24928630
TI  - Tetrahydrocoptisine protects rats from LPS-induced acute lung injury.
AB  - Recent studies show that nuclear factor-kappa B (NF-kappaB) signaling pathway
      plays a key role in contributing to the development of lipopolysaccharide (LPS)
      induced acute lung injury (ALI). Tetrahydrocoptisine is one of the main active
      components of Chelidonium majus L. and has been described to be effective in
      suppressing inflammation. The aim of the present study is to evaluate the
      protective effect of tetrahydrocoptisine on LPS-induced ALI in rats and clarify
      its underlying mechanisms of action. We found that in vivo pretreatment with
      tetrahydrocoptisine to rats 30 min before inducing ALI by LPS markedly decreased
      the mortality rate, lung wet weight to dry weight ratio, and ameliorated lung
      pathological changes. Meanwhile, tetrahydrocoptisine significantly inhibited the
      increase of the amounts of inflammatory cells, total protein content, tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in the
      bronchoalveolar lavage fluids (BALFs). Furthermore, tetrahydrocoptisine inhibited
      myeloperoxidase (MPO) accumulation in lung tissue and alleviated TNF-alpha and IL
      6 production in serum. Additionally, immunohistochemistry showed that
      tetrahydrocoptisine efficiently reduced nuclear factor-kappa B (NF-kappaB)
      activation by inhibiting the translocation of NF-kappaBp65. In conclusion, our
      results demonstrate that tetrahydrocoptisine possesses a protective effect on LPS
      induced ALI through inhibiting of NF-kappaB signaling pathways, which may involve
      the inhibition of pulmonary inflammatory process. 

PMID- 24928632
TI  - A pilot study examining functional brain activity 6 months after memory
      retraining in MS: the MEMREHAB trial.
AB  - Cognitive impairment in individuals with multiple sclerosis (MS) is now well
      recognized. One of the most common cognitive deficits is found in memory
      functioning, largely due to impaired acquisition. We examined functional brain
      activity 6 months after memory retraining in individuals with MS. The current
      report presents long term follow-up results from a randomized clinical trial on a
      memory rehabilitation protocol known as the modified Story Memory Technique.
      Behavioral memory performance and brain activity of all participants were
      evaluated at baseline, immediately after treatment, and 6 months after treatment.
      Results revealed that previously observed increases in patterns of cerebral
      activation during learning immediately after memory training were maintained 6
      months post training. 

PMID- 24928633
TI  - A chloroplast tree for Viburnum (Adoxaceae) and its implications for phylogenetic
      classification and character evolution.
AB  - * Premise of the study: Despite recent progress, significant uncertainties remain
      concerning relationships among early-branching lineages within Viburnum
      (Adoxaceae), prohibiting a new classification and hindering studies of character
      evolution and the increasing use of Viburnum in addressing a wide range of
      ecological and evolutionary questions. We hoped to resolve these issues by
      sequencing whole plastid genomes for representative species and combining these
      with molecular data previously obtained from an expanded taxon sample.* Methods:
      We performed paired-end Illumina sequencing of plastid genomes of 22 Viburnum
      species and combined these data with a 10-gene data set to infer phylogenetic
      relationships for 113 species. We used the results to devise a comprehensive
      phylogenetic classification and to analyze the evolution of eight morphological
      characters that vary among early-branching lineages.* Key results: With greatly
      increased levels of confidence in most of the early branches, we propose a
      phylogenetic classification of Viburnum, providing formal phylogenetic
      definitions for 30 clades, including 13 with names recognized under the
      International Code of Nomenclature for Algae, Fungi, and Plants, eight with
      previously proposed informal names, and nine newly proposed names for major
      branches. Our parsimony reconstructions of bud structure, leaf margins,
      inflorescence form, ruminate endosperm, extrafloral nectaries, glandular
      trichomes, palisade anatomy, and pollen exine showed varying levels of homoplasy,
      but collectively provided morphological support for some, though not all, of the
      major clades.* Conclusions: Our study demonstrates the value of next-generation
      plastid sequencing, the ease of creating a formal phylogenetic classification,
      and the utility of such a system in describing patterns of character evolution.

PMID- 24928635
TI  - Transgenic sexing system for genetic control of the Australian sheep blow fly
      Lucilia cuprina.
AB  - The New World screwworm and the Australian sheep blowfly Lucilia cuprina are
      devastating pests of livestock. The larvae of these species feed on the tissue of
      the living animal and can cause death if untreated. The sterile insect technique
      or SIT was used to eradicate screwworm from North and Central America. This
      inspired efforts to develop strains containing complex chromosomal rearrangements
      for genetic control of L. cuprina in Australia. Although one field trial was
      promising, the approach was abandoned due to costs and difficulties in mass
      rearing the strain. As the efficiency of SIT can be significantly increased if
      only sterile males are released, we have developed transgenic strains of L.
      cuprina that carry a dominant tetracycline repressible female lethal genetic
      system. Lethality is due to overexpression of an auto-regulated tetracycline
      repressible transactivator (tTA) gene and occurs mostly at the pupal stage.
      Dominant female lethality was achieved by replacing the Drosophila hsp70 core
      promoter with a Lucilia hsp70 core promoter-5'UTR for tTA overexpression. The
      strains carry a dominant strongly expressed marker that will facilitate
      identification in the field. Interestingly, the sexes could be reliably sorted by
      fluorescence or color from the early first instar larval stage as females that
      overexpress tTA also overexpress the linked marker gene. Male-only strains of L.
      cuprina developed in this study could form the basis for a future genetic control
      program. Moreover, the system developed for L. cuprina should be readily
      transferrable to other major calliphorid livestock pests including the New and
      Old World screwworm. 

PMID- 24928634
TI  - Preoperative estimated glomerular filtration rate and the risk of major adverse
      cardiovascular and cerebrovascular events in non-cardiac surgery.
AB  - BACKGROUND: Chronic kidney disease is an independent predictor of perioperative
      cardiovascular morbidity and mortality. We analysed the preoperative estimated
      glomerular filtration rate (eGFR) as a risk factor for perioperative major
      adverse cardiovascular and cerebrovascular events (MACCE) in non-cardiac surgery.
      METHODS: In a post hoc analysis of the ANESCARDIOCAT database, patients were
      classified into six stages of eGFR calculated with the abbreviated Modification
      of Diet in Renal Disease Study and the Chronic Kidney Disease Epidemiology
      Collaboration equations: >90 (1), 60-89.9 (2), 45-59.9 (3a), 30-44.9 (3b), 15
      29.9 (4), and <15 (5) ml min(-1) 1.73 m(-2). We analysed differences in MACCE,
      length of hospital stay, and all-cause mortality between eGFR stages. RESULTS:
      The eGFR was available in 2323 patients. Perioperative MACCE occurred in 4.5% of
      patients and cardiac-related mortality was 0.5%. Five hundred and forty-three
      (23.4%) patients had an eGFR of <60 ml min(-1) 1.73 m(-2) and 127 (5.4%) had an
      eGFR below 45 ml min(-1) 1.73 m(-2). Logistic regression analysis showed that
      MACCE increased with eGFR impairment (P<0.001), with a marked increase from stage
      3b onwards (odds ratio 1.8 vs 3.9 in 3a and 3b, respectively, P=0.047). All-cause
      mortality was not related to eGFR (P=0.071), but increased substantially between
      stages 3b and 4. The length of stay correlated with eGFR (P<0.001). CONCLUSIONS:
      Perioperative MACCE increase with declining eGFR, primarily when <45 ml min(-1)
      1.73 m(-2). We recommend the use of preoperative eGFR for cardiovascular risk
      assessment.

PMID- 24928636
TI  - Effect of spinal manipulation thrust magnitude on trunk mechanical activation
      thresholds of lateral thalamic neurons.
AB  - OBJECTIVES: High-velocity low-amplitude spinal manipulation (HVLA-SM), as
      performed by doctors who use manual therapy (eg, doctors of chiropractic and
      osteopathy), results in mechanical hypoalgesia in clinical settings. This
      hypoalgesic effect has previously been attributed to alterations in peripheral
      and/or central pain processing. The objective of this study was to determine
      whether thrust magnitude of a simulated HVLA-SM alters mechanical trunk response
      thresholds in wide dynamic range (WDR) and/or nociceptive specific (NS) lateral
      thalamic neurons. METHODS: Extracellular recordings were carried out in the
      thalamus of 15 anesthetized Wistar rats. Lateral thalamic neurons having
      receptive fields, which included the lumbar dorsal-lateral trunk, were
      characterized as either WDR (n=22) or NS (n=25). Response thresholds to
      electronic von Frey (rigid tip) mechanical trunk stimuli were determined in 3
      directions (dorsal-ventral, 45 degrees  caudalward, and 45 degrees  cranialward)
      before and immediately after the dorsal-ventral delivery of a 100-millisecond
      HVLA-SM at 3 thrust magnitudes (control, 55%, 85% body weight). RESULTS: There
      was a significant difference in mechanical threshold between 85% body weight
      manipulation and control thrust magnitudes in the dorsal-ventral direction in NS
      neurons (P=.01). No changes were found in WDR neurons at either HVLA-SM thrust
      magnitude. CONCLUSIONS: This study is the first to investigate the effect of HVLA
      SM thrust magnitude on WDR and NS lateral thalamic mechanical response threshold.
      Our data suggest that, at the single lateral thalamic neuron level, there may be
      a minimal spinal manipulative thrust magnitude required to elicit an increase in
      trunk mechanical response thresholds.

PMID- 24928637
TI  - The role of preload forces in spinal manipulation: experimental investigation of
      kinematic and electromyographic responses in healthy adults.
AB  - OBJECTIVES: Previous studies have identified preload forces and an important
      feature of skillful execution of spinal manipulative therapy (SMT) as performed
      by manual therapists (eg, doctors of chiropractic and osteopathy). It has been
      suggested that applying a gradual force before the thrust increases the spinal
      unit stiffness, minimizing displacement during the thrust. Therefore, the main
      objective of this study was to assess the vertebral unit biomechanical and
      neuromuscular responses to a graded increase of preload forces. METHODS: Twenty
      three participants underwent 4 different SMT force-time profiles delivered by a
      servo-controlled linear actuator motor and varying in their preload forces,
      respectively, set to 5, 50, 95, and 140N in 1 experimental session. Kinematic
      markers were place on T6, T7, and T8 and electromyographic electrodes were
      applied over paraspinal muscles on both sides of the spine. RESULTS: Increasing
      preload forces led to an increase in neuromuscular responses of thoracic
      paraspinal muscles and vertebral segmental displacements during the preload phase
      of SMT. Increasing the preload force also yielded a significant decrease in
      sagittal vertebral displacement and paraspinal muscle activity during and
      immediately after the thrust phase of spinal manipulation. Changes observed
      during the SMT thrust phase could be explained by the proportional increase in
      preload force or the related changes in rate of force application. Although only
      healthy participants were tested in this study, preload forces may be an
      important parameter underlying SMT mechanism of action. Future studies should
      investigate the clinical implications of varying SMT dosages. CONCLUSION: The
      present results suggest that neuromuscular and biomechanical responses to SMT may
      be modulated by preload through changes in the rate of force application.
      Overall, the present results suggest that preload and rate of force application
      may be important parameters underlying SMT mechanism of action.

PMID- 24928638
TI  - Instantaneous rate of loading during manual high-velocity, low-amplitude spinal
      manipulations.
AB  - OBJECTIVE: The objective of this study was to determine the instantaneous rate of
      loading during manual high-velocity, low-amplitude spinal manipulations (HVLA
      SMs) in the lumbar and thoracic regions and compare to the average rates of
      loading. METHODS: Force-time profiles were recorded using a hand force transducer
      placed between the hand of a doctor of chiropractic and the subject's back during
      14 HVLA SM thrusts on asymptomatic volunteers while 3 doctors of chiropractic
      delivered the spinal manipulations. Doctors also delivered 36 posterior to
      anterior thoracic manipulations on a mannequin. Data were collected at a sampling
      rate of 1000 Hz using Motion Monitor software. Force-time profile data were
      differentiated to obtain instantaneous rates of loading. The data were reduced
      using a custom-written MathCad program and analyzed descriptively. RESULTS: The
      instantaneous rates of loading were 1.7 to 1.8 times higher than average rates of
      loading, and instantaneous rates of unloading were 2.1 to 2.6 times the average
      rates of unloading during HVLA SMs. Maximum instantaneous rates of loading
      occurred 102 to 111 milliseconds prior to peak load. Maximum instantaneous rates
      of unloading occurred 121 to 154 milliseconds after the peak load. These data may
      be useful for further understanding of HVLA SMs. CONCLUSIONS: The instantaneous
      rates of loading and where they occurred may be useful data for understanding and
      describing HVLA SMs.

PMID- 24928639
TI  - Cost analysis related to dose-response of spinal manipulative therapy for chronic
      low back pain: outcomes from a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this analysis is to report the incremental costs and
      benefits of different doses of spinal manipulative therapy (SMT) in patients with
      chronic low back pain (LBP). METHODS: We randomized 400 patients with chronic LBP
      to receive a dose of 0, 6, 12, or 18 sessions of SMT. Participants were scheduled
      for 18 visits for 6 weeks and received SMT or light massage control from a doctor
      of chiropractic. Societal costs in the year after study enrollment were estimated
      using patient reports of health care use and lost productivity. The main health
      outcomes were the number of pain-free days and disability-free days. Multiple
      regression was performed on outcomes and log-transformed cost data. RESULTS: Lost
      productivity accounts for most societal costs of chronic LBP. Cost of treatment
      and lost productivity ranged from $3398 for 12 SMT sessions to $3815 for 0 SMT
      sessions with no statistically significant differences between groups. Baseline
      patient characteristics related to increase in costs were greater age (P = .03),
      greater disability (P = .01), lower quality-adjusted life year scores (P = .01),
      and higher costs in the period preceding enrollment (P < .01). Pain-free and
      disability-free days were greater for all SMT doses compared with control, but
      only SMT 12 yielded a statistically significant benefit of 22.9 pain-free days (P
      = .03) and 19.8 disability-free days (P = .04). No statistically significant
      group differences in quality-adjusted life years were noted. CONCLUSIONS: A dose
      of 12 SMT sessions yielded a modest benefit in pain-free and disability-free
      days. Care of chronic LBP with SMT did not increase the costs of treatment plus
      lost productivity.

PMID- 24928640
TI  - Changes in kinetic, kinematic, and temporal parameters of walking in people with
      limited ankle dorsiflexion: pre-post application of modified mobilization with
      movement using talus glide taping.
AB  - OBJECTIVE: The purpose of this study was to investigate the changes in passive
      ankle dorsiflexion range of motion (ROM), maximum plantar force, force-time
      integral, and time to heel off during walking between pre- and postapplication of
      modified mobilization with movement (MWM) using talus glide taping in people with
      limited ankle dorsiflexion. METHODS: Eighteen feet with limited ankle
      dorsiflexion in 13 people were examined. Participants performed 3 different
      walking tasks in the following order: walking before and immediately after
      applying the modified MWM using talus glide taping and walking after 5-minute
      walking with the modified MWM using talus glide taping. A floor-mat pressure
      measurement system (HR-mat) was used to measure maximum plantar force, force-time
      integral, and time to heel off; and passive ankle dorsiflexion ROM was measured
      using a standard goniometer. The significance of differences was assessed using
      repeated one-way analysis of variance. RESULTS: Passive ankle dorsiflexion ROM
      and time to heel off were significantly increased after 5-minute walking with the
      modified MWM using talus glide taping compared with walking before and
      immediately after applying the tape. Significantly increased maximum plantar
      force and force-time integral on the hindfoot and significantly decreased force
      time integral on the forefoot during walking after 5-minute walking were observed
      with the modified MWM using talus glide taping compared with before applying the
      tape. No significant difference between before and immediately after applying the
      tape was observed in any variable. CONCLUSIONS: Our results suggest that walking
      an additional 5-minute with the modified MWM using talus glide taping increased
      passive ankle dorsiflexion ROM and time to heel off and improved dynamic plantar
      loading during walking.

PMID- 24928641
TI  - Assessment of paraspinal muscle hardness in subjects with a mild single scoliosis
      curve: a preliminary myotonometer study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the hardness of the
      paraspinal muscles in the convexity and concavity of patients with scoliosis
      curvatures and in the upper trapezius (UT) muscle in subjects with mild
      idiopathic scoliosis (IS) and to observe the correlation between the myotonometer
      (MYO) measurements and the value of body mass index (BMI) and the Cobb angle.
      METHODS: The sample included 13 patients with a single-curve mild IS (Risser sign
      <= 4) at thoracic, lumbar, or thoracolumbar level (mean Cobb angle of 11.53o).
      Seven females and 6 males were recruited, with a mean age of 12.84 +/- 3.06 (9
      18) years. A MYO was used to examine the differences in muscle hardness on both
      sides of the scoliosis curvature at several points: (a) apex of the curve, (b)
      upper and lower limits of the curve, and (c) the midpoint between the apex and
      the upper limit and between the apex and the lower limit. The UT was also
      explored. RESULTS: Although the MYO recorded lower values in all points on the
      concave side of the scoliosis, there were no significant differences in the
      comparison between sides (P > .05). No association was observed between BMI and
      MYO values, whereas the Cobb angle negatively correlated with muscle hardness
      only at 2 points on the convex side. CONCLUSION: The preliminary findings show
      that, in subjects with a single-curve mild IS, muscular hardness in the UT and
      paraspinal muscles, as assessed using a MYO, was not found to differ between the
      concave and the convex sides at different reference levels.

PMID- 24928642
TI  - Evaluation of the usefulness of 2 prediction models of clinical prediction models
      in physical therapy: a qualitative process evaluation.
AB  - OBJECTIVE: The purposes of this study were to (1) evaluate the usefulness of 2
      prediction models by assessing the actual use and advantages/disadvantages of
      application in daily clinical practice and (2) propose recommendations to enhance
      their implementation. METHODS: Physical therapists working in 283 practices in
      the area of Breda (the Netherlands) were invited to participate in this study.
      Two prediction models were presented: (1) to predict persistent shoulder pain and
      (2) to predict the preferable treatment in nonspecific neck pain. Participants
      were asked to apply both models in practice. After 2 months, their opinions about
      the usefulness of both models were gathered during a focus group meeting or by
      using an online questionnaire in order to identify the most important
      advantages/disadvantages of each prediction model. RESULTS: In total, 46 physical
      therapists (13.8%) of 39 practices participated. Evaluative data were available
      from 32 participants who used the shoulder model 102 times and the neck model 126
      times. For the shoulder model, the most frequent advantage (mentioned 14 times)
      was that it enabled physical therapists to estimate a motivated prognosis, that
      is, a prognosis based on the score of the model. The most frequent mentioned
      disadvantage was that participants expressed their doubts about the validity of
      the model because the model initially was developed for usage in a general
      practice setting. For the neck model, the most frequently mentioned advantage (29
      times) was that the model was easy to interpret. The most important disadvantage
      (mentioned 14 times) was that the model only takes a few treatment options into
      account. CONCLUSIONS: The physical therapists participating in this study
      reported that both models evaluated in this study were not easy to use in daily
      practice. Based on the findings of this study, we recommend that these models are
      modified to meet the practical needs of the therapist, before assessing their
      impact on daily clinical care and patient outcomes.

PMID- 24928643
TI  - Replacement of the heavily calcified ascending aorta in aortic valve replacement.
AB  - A totally calcified ascending aorta prevents aortic crossclamping and aortotomy
      during aortic valve replacement, and replacement of the ascending aorta is a
      valid option in these cases. We describe a simple technique for calcified
      ascending aorta replacement using the Cavitron Ultrasonic Surgical Aspirator.
      This can be used in aortic endarterectomy for removal of the calcified plaque in
      the anastomotic part. 

PMID- 24928644
TI  - Is bilateral chylothorax possible after simple cough? Yes.
AB  - Chylothorax is accumulation of chylous fluid in the pleural space due to impaired
      integrity of the thoracic duct or its branches. In childhood, the causes differ
      from those in adults because children less frequently develop malignancies and
      are more resistant to trauma. Commonly, chylothorax occurs as a complication of
      tumoral invasion or cardiopulmonary surgery. Treatment of chylothorax is
      essentially medical. In the event of medical treatment failure or a massive
      effusion, surgery is needed. We describe the case of a 65-year-old woman who
      developed bilateral chylothorax after a simple cough. She was treated with a
      medium-chain triglyceride diet and thoracentesis. 

PMID- 24928645
TI  - Thoracoscopic wedge lung resection using virtual-assisted lung mapping.
AB  - BACKGROUND: Virtual-assisted lung mapping is a novel bronchoscopic preoperative
      lung marking technique using virtual images to conduct multiple concurrent lung
      markings with dye. This study analyzed the indications, mapping design, and
      outcomes of lung wedge resection using virtual-assisted lung mapping. METHODS:
      From August 2012 to October 2013, 35 patients with 59 lesions were planned to
      undergo thoracoscopic lung wedge resection aided by virtual-assisted lung
      mapping. The data related to virtual-assisted lung mapping were prospectively
      collected, with the exception of the mapping design which was retrospectively
      analyzed. RESULTS: Suspected primary lung cancer (21 lesions in 18 patients) and
      metastatic lung tumors (38 lesions in 17 patients) were treated by thoracoscopic
      lung wedge resection with the aid of virtual-assisted lung mapping; 50 wedge
      resections were conducted with 107 markings. Virtual-assisted lung mapping was
      most frequently designed to place 2 (n = 15 wedge resections) or 3 (n = 17)
      markings to both identify the tumor(s) and secure a sufficient resection margin.
      In 7 wedge resections, anatomical landmarks and/or imaginary auxiliary lines
      functioned as complementary parts of the lung map when bronchial anatomy did not
      allow for markings at ideal spots. The resection outcomes were satisfactory
      without clinically evident complications. CONCLUSION: Multiple markings of
      virtual-assisted lung mapping not only enabled tumor identification, but also
      secured sufficient resection margins. Special techniques using anatomical
      landmarks and imaginary auxiliary lines were complementary to the lung map when
      bronchial anatomy did not allow for markings at ideal spots.

PMID- 24928646
TI  - Total arch replacement for coarctation of the aorta in an adolescent.
AB  - A 16-year-old boy suffered a subarachnoid hemorrhage and underwent open head
      surgery. He was subsequently diagnosed with coarctation of the aorta and referred
      to our hospital. The coarctation was at the distal transverse arch, just at the
      site of branching of the subclavian artery. Total arch replacement with selective
      cerebral perfusion was selected because of the short hypoplastic arch. The
      patient had an uneventful postoperative course, and was doing well 3 years after
      the surgery. 

PMID- 24928647
TI  - Lung function decline and variable airway inflammatory pattern: longitudinal
      analysis of severe asthma.
AB  - BACKGROUND: Eosinophilic airway inflammation measured by using induced sputum is
      an important treatment stratification tool in patients with severe asthma. In
      addition, sputum eosinophilia has been shown to be associated with severe
      exacerbations and airflow limitation. OBJECTIVES: We sought to identify whether
      eosinophilic inflammation in sputum is associated with FEV1 decrease in patients
      with severe asthma and whether we could identify subgroups of decrease behavior
      based on the variation of eosinophilic airway inflammation over time. METHODS:
      Ninety-seven patients with severe asthma from the Glenfield Asthma Cohort were
      followed up with scheduled 3-month visits; the median duration of follow-up and
      number of visits was 6 years (interquartile range, 5.6-7.6 years) and 2.7 visits
      per year. Induced sputum was analyzed for eosinophilic inflammation at scheduled
      visits. Linear mixed-effects models were used to identify variables associated
      with lung function and overall decrease. In addition, using individual patients'
      mean and SD sputum eosinophil percentages over time, a 2-step cluster analysis
      was performed to identify patient clusters with different rates of decrease.
      RESULTS: FEV1 decrease was -25.7 mL/y in the overall population.
      Postbronchodilator FEV1 was also dependent on exacerbations, age of onset,
      height, age, sex, and log10 sputum eosinophil percentages (P < .001). Three
      decrease patient clusters were identified: (1) noneosinophilic with low variation
      (mean decrease, -14.0 mL/y), (2) eosinophilic with high variation (mean decrease,
      -40.9 mL/y), and (3) hypereosinophilic with low variation (mean decrease in lung
      function, -19.2 mL/y). CONCLUSION: The amplitude of sputum eosinophilia was
      associated with postbronchodilator FEV1 in asthmatic patients. In contrast, high
      variability rather than the amplitude at baseline or over time of sputum
      eosinophils was associated with accelerated FEV1 decrease.

PMID- 24928649
TI  - Comparison of complication rates associated with permanent and retrievable
      inferior vena cava filters: a review of the MAUDE database.
AB  - PURPOSE: To compare the safety of permanent and retrievable inferior vena cava
      (IVC) filters by reviewing the U.S. Food and Drug Administration Manufacturer and
      User Facility Device Experience (MAUDE) database. MATERIALS AND METHODS: The
      MAUDE database was reviewed from January 1, 2009, to December 31, 2012. Product
      class search criteria were "filter, intravascular, cardiovascular." Type of
      device used and specific adverse events (AEs) were recorded. RESULTS: For the
      period January 2009-December 2012, 1,606 reported AEs involving 1,057 IVC filters
      were identified in the MAUDE database . Of reported AEs, 1,394 (86.8%) involved
      retrievable inferior vena cava filters (rIVCFs), and 212 (13.2%) involved
      permanent inferior vena cava filters (pIVCFs) (P < .0001). Reported AEs included
      fracture, migration, limb embolization, tilt, IVC penetration, venous
      thromboembolism and pulmonary embolism, IVC thrombus, and malfunctions during
      placement. Each specific AE was reported with significantly higher frequency in
      rIVCFs compared with pIVCFs. The most common reported complication with rIVCFs
      was fracture, whereas the most commonly reported complications with pIVCFs were
      placement malfunctions. For rIVCFs, the most commonly reported AE varied
      depending on filter brand. CONCLUSIONS: The MAUDE database reveals that
      complications occur with significantly higher frequency with rIVCFs compared with
      pIVCFs. This finding suggests that the self-reported complication rate with
      rIVCFs is significantly higher than the self-reported complication rate with
      pIVCFs.

PMID- 24928648
TI  - Airway surface mycosis in chronic TH2-associated airway disease.
AB  - BACKGROUND: Environmental fungi have been linked to TH2 cell-related airway
      inflammation and the TH2-associated chronic airway diseases asthma, chronic
      rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal
      rhinosinusitis (AFRS), but whether these organisms participate directly or
      indirectly in disease pathology remains unknown. OBJECTIVE: To determine the
      frequency of fungus isolation and fungus-specific immunity in patients with TH2
      associated and non-TH2-associated airway disease. METHODS: Sinus lavage fluid and
      blood were collected from sinus surgery patients (n = 118) including patients
      with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non
      CRS/nonasthmatic control patients. Asthma status was determined from medical
      history. Sinus lavage fluids were cultured and directly examined for evidence of
      viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked
      immunocell spot assay to determine total memory fungus-specific IL-4-secreting
      cells. These data were compared with fungus-specific IgE levels measured from
      plasma by ELISA. RESULTS: Filamentous fungi were significantly more commonly
      cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS:
      n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs
      16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell
      spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated
      diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively).
      CONCLUSIONS: The frequent isolation of fungi growing directly within the airways
      accompanied by specific immunity to these organisms only in patients with TH2
      associated chronic airway diseases suggests that fungi participate directly in
      the pathogenesis of these conditions. Efforts to eradicate airway fungi from the
      airways should be considered in selected patients.

PMID- 24928650
TI  - Leukopak PBMC sample processing for preparing quality control material to support
      proficiency testing programs.
AB  - External proficiency testing programs designed to evaluate the performance of end
      point laboratories involved in vaccine and therapeutic clinical trials form an
      important part of clinical trial quality assurance. Good clinical laboratory
      practice (GCLP) guidelines recommend both assay validation and proficiency
      testing for assays being used in clinical trials, and such testing is facilitated
      by the availability of large numbers of well-characterized test samples. These
      samples can be distributed to laboratories participating in these programs and
      allow monitoring of laboratory performance over time and among participating
      sites when results are obtained with samples derived from a large master set. The
      leukapheresis procedure provides an ideal way to collect samples from
      participants that can meet the required number of cells to support these
      activities. The collection and processing of leukapheresis samples require tight
      coordination between the clinical and laboratory teams to collect, process, and
      cryopreserve large number of samples within the established ideal time of <=8
      hours. Here, we describe our experience with a leukapheresis cryopreseration
      program that has been able to preserve the functionality of cellular subsets and
      that provides the sample numbers necessary to run an external proficiency testing
      program.

PMID- 24928651
TI  - Mining biomass-degrading genes through Illumina-based de novo sequencing and
      metagenomic analysis of free-living bacteria in the gut of the lower termite
      Coptotermes gestroi harvested in Vietnam.
AB  - The 5.6 Gb metagenome of free-living microbial flora in the gut of the lower
      termite Coptotermes gestroi, harvested in Vietnam, was sequenced using Illumina
      technology. Genes related to biomass degradation were mined for a better
      understanding of biomass digestion in the termite gut and to identify
      lignocellulolytic enzymes applicable to biofuel production. The sequencing
      generated 5.4 Gb of useful reads, containing 125,431 ORFs spanning 78,271,365 bp,
      80% of which was derived from bacteria. The 12 most abundant bacterial orders
      were Spirochaetales, Lactobacillales, Bacteroidales, Clostridiales,
      Enterobacteriales, Pseudomonades, Synergistales, Desulfovibrionales,
      Xanthomonadales, Burkholderiales, Bacillales, and Actinomycetales, and 1460
      species were estimated. Of more than 12,000 ORFs with predicted functions related
      to carbohydrate metabolism, 587 encoding hydrolytic enzymes for cellulose,
      hemicellulose, and pectin were identified. Among them, 316 ORFs were related to
      cellulose degradation, and included beta-glucosidases, 6-phospho-beta
      glucosidases, licheninases, glucan endo-1,3-beta-D-glucosidases, endoglucanases,
      cellulose 1,4-beta-cellobiosidases, glucan 1,3-beta-glucosidases, and cellobiose
      phosphorylases. In addition, 259 ORFs were related to hemicellulose degradation,
      encoding endo-1,4-beta-xylanases, alpha-galactosidases, alpha-N
      arabinofuranosidases, xylan 1,4-beta-xylosidases, arabinan endo-1,5-alpha-L
      arabinosidases, endo-1,4-beta-mannanases, and alpha-glucuronidases. Twelve ORFs
      encoding pectinesterases and pectate lyases were also obtained. To our knowledge,
      this is the first successful application of Illumina-based de novo sequencing for
      the analysis of a free-living bacterial community in the gut of a lower termite
      C. gestroi and for mining genes related to lignocellulose degradation from the
      gut bacteria.

PMID- 24928652
TI  - Effect of fluorescent lighting on the color of liquid-crystal displays.
AB  - Liquid-crystal displays (LCDs) are used for displaying medical images under
      various illuminance conditions and with ambient-lighting colors. Our purpose in
      this study was to understand the variations of the chromaticity in LCDs under
      different fluorescent lighting conditions. The variation of chromaticity of LCDs
      at a white point consisting of equivalent pixel value in Red, Green, and Blue was
      examined under different types of fluorescent lighting. The direction of changes
      in the chromaticity diagram shifted to the color of each fluorescent lighting.
      When the differences in chromaticity (?u'v') increased, the observers' confidence
      levels in distinguishing color differences also increased. When the luminance of
      the LCD increased, observers' sensitivities for recognizing differences in
      chromaticity also increased as compared to observers' sensitivities at lower
      luminances. Our results indicate that observers recognized slightly yellowish
      colors even if ?u'v' was less than 0.01; thus, observers could perceive
      differences in chromaticity. These results could provide important and relevant
      information with regard to better ambient lighting conditions in an image-reading
      room.

PMID- 24928653
TI  - Mapping biological entities using the longest approximately common prefix method.
AB  - BACKGROUND: The significant growth in the volume of electronic biomedical data in
      recent decades has pointed to the need for approximate string matching algorithms
      that can expedite tasks such as named entity recognition, duplicate detection,
      terminology integration, and spelling correction. The task of source integration
      in the Unified Medical Language System (UMLS) requires considerable expert effort
      despite the presence of various computational tools. This problem warrants the
      search for a new method for approximate string matching and its UMLS-based
      evaluation. RESULTS: This paper introduces the Longest Approximately Common
      Prefix (LACP) method as an algorithm for approximate string matching that runs in
      linear time. We compare the LACP method for performance, precision and speed to
      nine other well-known string matching algorithms. As test data, we use two
      multiple-source samples from the Unified Medical Language System (UMLS) and two
      SNOMED Clinical Terms-based samples. In addition, we present a spell checker
      based on the LACP method. CONCLUSIONS: The Longest Approximately Common Prefix
      method completes its string similarity evaluations in less time than all nine
      string similarity methods used for comparison. The Longest Approximately Common
      Prefix outperforms these nine approximate string matching methods in its Maximum
      F1 measure when evaluated on three out of the four datasets, and in its average
      precision on two of the four datasets.

PMID- 24928654
TI  - Biofiltration of high formaldehyde loads with ozone additions in long-term
      operation.
AB  - Formaldehyde (FA) biofiltration was evaluated over 310 days with and without
      ozone addition. Without ozone, the biofilter was able to treat formaldehyde at
      inlet loads (ILs) lower than 40 g m(-3) h(-1), maintaining, under this condition,
      an average removal efficiency (RE) of 88 % for a few days before collapsing to
      zero. The continuous addition of ozone (90 ppbv) helped to recover the RE from
      zero to 98 +/- 2 % and made it possible to operate at an IL of 40 g m(-3) h(-1)
      for long periods of operation (107 days). Furthermore, the ozone addition aided
      in operating the biofilter at a formaldehyde IL of up to 120 g m(-3) h(-1) values
      that have never before been reached. GC-mass spectrometry (MS) analysis showed
      that dimethoxymethane was the common compound in leachate during the performance
      decay. Also, the addition of ozone aided in maintaining an optimal pH in the
      biofilter with values between 7.5 and 8.2, due to the carbonate species formed
      during the ozone reactions with formaldehyde and its by-products. Thus, the pH
      control was confirmed and the alkalinity of the biofilter increased from 334.1 +/
      100.3 to 1450 +/- 127 mg CaCO3 L(-1) when ozone was added. Ozone addition
      diminished the exopolymeric substances (EPS) content of biofilm and biofilm
      thickness without affecting cell viability. Kinetic parameters suggested that the
      best conditions for carrying out FA biofiltration were reached under ozone
      addition. The addition of ozone during formaldehyde biofiltration could be a good
      strategy to maintain the pH and the steady state of the system under high ILs and
      for long periods of operation. 

PMID- 24928655
TI  - Heterologous production of horseradish peroxidase C1a by the basidiomycete yeast
      Cryptococcus sp. S-2 using codon and signal optimizations.
AB  - In the present study, we attempted to improve the production of recombinant
      horseradish peroxidase C1a (HRP-C1a; a heme-binding protein) by Cryptococcus sp.
      S-2. Both native and codon-optimized HRP-C1a genes were expressed under the
      control of a high-level expression promoter. When the HRP-C1a gene with native
      codons was expressed, poly(A) tails tended to be added within the coding region,
      producing truncated messenger RNAs (mRNAs) that lacked the 3' ends. Codon
      optimization prevented polyadenylation within the coding region and increased
      both the mRNA and protein levels of active HRP-C1a. To improve secretion of the
      recombinant protein, we tested five types of N-terminal signal peptide (NTP).
      These included the native HRP-C1a NTP (C1a-NTP), short and long xylanase
      secretion signals (X1-NTP and X2-NTP), cutinase signal (C-NTP), and amylase
      signal (A-NTP), with and without a C-terminal propeptide (CTP). X2-NTP without
      CTP resulted in the highest HRP-C1a secretion into the culture medium. HRP-C1a
      secretion was further increased by using xylose fed-batch fermentation. The
      production of HRP-C1a in this study was 2.7 and 15 times higher than the
      production reported in previous studies that used insect cell and Pichia
      expression systems, respectively. 

PMID- 24928656
TI  - Formation of filamentous aerobic granules: role of pH and mechanism.
AB  - Filamentous overgrowth in aerobic granular sludge processes can cause reactor
      failure. In this work, aerobic granules were cultivated in five identical
      sequencing batch reactors with acetate or glucose as the carbon source with
      various values of influent pH (4.5-8). Microscopic observations revealed that
      acidic pH, rather than the species of carbon source, epistatically controls the
      aerobic granules with filamentous structure. An acidic pH shifted the structure
      of the microbial community in the granules, such that the fungus Geotrichum
      fragrans was the predominant filamentous microorganism therein. The acidic pH
      reduced the intracellular cyclic diguanylate (c-di-GMP) content for increasing
      the motility of the bacteria to washout and increase the growth rate of G.
      fragrans on glucose or acetate, together causing overgrowth of the fungus.
      Maintaining the suspension under alkaline condition is proposed as an effective
      way to suppress filamentous overgrowth and maintain granule stability. 

PMID- 24928657
TI  - Removal of Cr(VI) from aqueous solutions by fruiting bodies of the jelly fungus
      (Auricularia polytricha).
AB  - The aim of this study was to investigate the potential to remove chromium (Cr)
      from aqueous solutions using the fruiting body of Auricularia polytricha. Batch
      experiments were conducted under various conditions, and different models were
      used to characterize the biosorption process. Results showed that, for both fresh
      and dried fruiting bodies of A. polytricha, removal efficiencies of Cr(VI) and
      total Cr reached maximum values at pH values of 1 and 2, respectively. The
      process of Cr(VI) removal by A. polytricha included the sorption process as well
      as the reduction of Cr(VI) to Cr(III). Spectra of X-ray photoelectron
      spectroscopy of the biosorbent revealed that most of the Cr loaded on the biomass
      surface was in the trivalent form. The Freundlich model fitted the isotherm
      process better than the Langmuir model in the concentration range examined. The
      pseudo-second-order model well described the adsorption process of Cr onto the
      biomass. The biosorption capacity of Cr(VI) by fruiting bodies was much higher
      than that by most of other biosorbents reported. The results suggest that the
      fruiting bodies of A. polytricha should be a promising biomaterial for Cr removal
      from water contaminated by the heavy metal. 

PMID- 24928658
TI  - Interactions between Verticillium dahliae and its host: vegetative growth,
      pathogenicity, plant immunity.
AB  - Verticillium dahliae is a soil-borne phytopathogenic fungus that causes vascular
      wilt diseases in a wide variety of crop plants, resulting in extensive economic
      losses. In the past 5 years, progress has been made in elaborating the
      interaction between this hemibiotrophic fungus and its host plants. Some genes
      responsible for the vegetative growth and/or pathogenicity in V. dahliae have
      been identified. Plants have accrued a series of defense mechanisms, including
      inducible defense signaling pathways and some resistant genes to combat V.
      dahliae infection. Here, we have reviewed the progress in V. dahliae-plant
      interaction research. 

PMID- 24928659
TI  - Molecular biology-based methods for quantification of bacteria in mixed culture:
      perspectives and limitations.
AB  - Species-specific enumeration of mixed community is invaluable as it facilitates a
      better understanding of the significance of the individual strains, their
      interactions, and the underlying mechanisms of community dynamics. Mixed
      microbial community has been characterized by microbiological, biochemical, or
      molecular biology-based methods. While microbiological and biochemical techniques
      do not provide adequate quantitative information of the members of the consortia
      and require additional techniques for a more comprehensive analysis, molecular
      biology-based methods analyze the microbial consortium based on specific DNA
      sequences and do not require isolation and culturing of bacteria for quantitative
      analysis. These methods outshine conventional culture-based techniques in terms
      of better sensitivity, reproducibility, and reliability. Quantitative molecular
      biology methods have been classified as PCR-based and probe hybridization
      methods. The PCR-based methods includes quantitative real-time PCR and terminal
      restriction fragment length polymorphism, while fluorescent in situ hybridization
      and DNA microarrays fall under probe hybridization methods. The workflow, the
      quantification methods, and their potential applications are discussed in this
      review by highlighting their advantages and possible limitations. 

PMID- 24928660
TI  - Screening of cry-type promoters with strong activity and application in Cry
      protein encapsulation in a sigK mutant.
AB  - To optimize the expression of cry genes in a Bacillus thuringiensis sigK mutant
      failing in crystal releasing, the transcriptional activity of the cry promoters
      cry1A, cry3A, cry4A, and cry8E was compared using lacZ gene fusions. A beta
      galactosidase assay indicated that the cry8E promoter showed the highest
      transcriptional activity. A novel Escherichia coli-B. thuringiensis shuttle
      vector pHT315-8E21b was constructed for cry gene expression using the cry8E
      promoter and the multiple cloning sites from vector pET21b, based on vector
      pHT315. SDS-PAGE analysis showed that the expression of the cry1Ac gene directed
      by the cry8E promoter was increased by approximately 2.4-fold over the expression
      directed by the cry3A promoter. The cry1Ba gene was expressed in the sigK mutant
      with the constructed vector pHT315-8E21b. Normal bipyramidal crystals
      encapsulated in mother cell were observed by transmission electron microscopy
      (TEM). The encapsulated Cry1Ba protein expressed in the sigK mutant showed
      activity against Ostrinia furnacalis and Plutella xylostella similar to that of
      the released Cry1Ba protein expressed in the acrystalliferous strain HD73 and can
      be protected from inactivation by UV light. All these results suggest that the
      cry8E promoter can be an efficient transcriptional element for cry gene
      expression in sigK mutants and can be utilized for the construction of a
      genetically engineered strain. 

PMID- 24928661
TI  - Association between serum vitamin D concentrations and inflammatory markers in
      the general adult population.
AB  - OBJECTIVE: In recent years links among vitamin D deficiency, inflammation and
      cardio-metabolic disease were proposed. As information regarding the associations
      between vitamin D and inflammatory markers in the general population is sparse,
      we investigated the associations of 25-hydroxy vitamin D [25(OH)D] with high
      sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cell count
      (WBC). MATERIALS/METHODS: The study population comprised 2723 men and women aged
      25-88 years from the first follow-up of the Study of Health in Pomerania.
      Analyses of variance, linear and logistic regressions were performed to assess
      the associations between 25(OH)D and the three inflammatory markers. The models
      were adjusted for age, sex, waist circumference, diabetes mellitus, dyslipidemia,
      anti-inflammatory medication and month of blood sampling. The association between
      25(OH)D and WBC was assessed separately in smokers (n = 718) and non-smokers (n =
      2005) as effect modification was observed. RESULTS: We detected a U-shaped
      association between 25(OH)D and hs-CRP with a nadir of 21-25 ng/ml in fully
      adjusted linear regression models with restricted cubic splines (p < 0.01; p' <
      0.01). We further detected an inverse association between 25(OH)D and fibrinogen
      (p < 0.01). In addition, there was an inverse association between 25(OH)D and WBC
      in smokers (p = 0.02) but no association in non-smokers (p = 0.73). CONCLUSION:
      Our study confirms a potential role of 25(OH)D in chronic inflammation. Yet,
      different inflammatory biomarkers are differently associated with 25(OH)D.
      Beneficial effects of increasing 25(OH)D were observed for fibrinogen and WBC (in
      smokers only). In contrast, the U-shaped association between 25(OH)D and hs-CRP
      indicates that ever-increasing 25(OH)D concentrations may also be related to
      proinflammatory states.

PMID- 24928662
TI  - Genome instability in Maple Syrup Urine Disease correlates with impaired
      mitochondrial biogenesis.
AB  - OBJECTIVE: The mitochondrial branched-chain ketoacid dehydrogenase (BCKD)
      catalyzes the degradation of branched-chain amino acids (BCAA), which have been
      shown to induce oxidative stress. Maple Syrup Urine Disease (MSUD) is caused by
      impaired activity of BCKD, suggesting that oxidative stress and resulting DNA
      damage could contribute to pathology. We evaluated the potential effect of BCKD
      deficiency on genome integrity and mitochondrial function as a downstream target.
      METHODS: Primary fibroblasts from MSUD patients and controls were either
      cultivated under normal conditions or exposed to metabolic or oxidative stress.
      DNA was analyzed for damage and mitochondrial function was evaluated by gene
      expression analyses, functional assays and immunofluorescent methods. RESULTS:
      Patient fibroblasts accumulated damage in mitochondrial DNA (mtDNA) and nuclear
      DNA, with a corresponding reduction in mitochondrial transcription, mtDNA copy
      number and pyruvate dehydrogenase. We found no evidence of increased level of
      reactive oxygen species (ROS) in patient fibroblasts under normal conditions,
      suggesting that the genotoxic effect is ascribed to accumulating metabolites.
      CONCLUSIONS: Impaired BCKD activity as in MSUD, results in accumulation of DNA
      damage and corresponding mitochondrial dysfunction.

PMID- 24928663
TI  - Estimation of the serial interval of pertussis in Dutch households.
AB  - Increasing incidence has led to the re-appearance of pertussis as a public health
      problem in developed countries. Pertussis infection is usually mild in vaccinated
      children and adults, but it can be fatal in infants who are too young for
      effective vaccination (<=3 months). Tailoring of control strategies to prevent
      infection of the infant hinges on the availability of estimates of key
      epidemiological quantities. Here we estimate the serial interval of pertussis,
      i.e., the time between symptoms onset in a case and its infector, using data from
      a household-based study carried out in the Netherlands in 2007-2009. We use
      statistical methodology to tie infected persons to probable infector persons, and
      obtain statistically supported stratifications of the data by person-type
      (infant, mother, father, sibling). The analyses show that the mean serial
      interval is 20 days (95% CI: 16-23 days) when the mother is the infector of the
      infant, and 28 days (95% CI: 23-33 days) when the infector is the father or a
      sibling. These time frames offer opportunities for early mitigation of the
      consequences of infection of an infant once a case has been detected in a
      household. If preventive measures such as social distancing or antimicrobial
      treatment are taken promptly they could decrease the probability of infection of
      the infant.

PMID- 24928664
TI  - An approach for modeling cross-immunity of two strains, with application to
      variants of Bartonella in terms of genetic similarity.
AB  - We developed a two-strain susceptible-infected-recovered (SIR) model that
      provides a framework for inferring the cross-immunity between two strains of a
      bacterial species in the host population with discretely sampled co-infection
      time-series data. Moreover, the model accounts for seasonality in host
      reproduction. We illustrate an approach using a dataset describing co-infections
      by several strains of bacteria circulating within a population of cotton rats
      (Sigmodon hispidus). Bartonella strains were clustered into three genetically
      close groups, between which the divergence is correspondent to the accepted level
      of separate bacterial species. The proposed approach revealed no cross-immunity
      between genetic clusters while limited cross-immunity might exist between
      subgroups within the clusters. 

PMID- 24928665
TI  - Modelling the effect of changes in vaccine effectiveness and transmission contact
      rates on pertussis epidemiology.
AB  - The incidence of the highly infectious respiratory disease named pertussis or
      whooping cough has been increasing for the past two decades in different
      countries, as in much of the highly vaccinated world. A decrease in vaccine
      effectiveness over time, especially when acellular vaccines were used for primary
      doses and boosters, and pathogen adaptation to the immunity conferred by vaccines
      have been proposed as possible causes of the resurgence. The contributions of
      these factors are not expected to be the same in different communities, and this
      could lead to different epidemiological trends. In fact, differences in the
      magnitude and dynamics of pertussis outbreaks as well as in the distribution of
      notified cases by age have been reported in various regions. Using an age
      structured mathematical model designed by us, we evaluated how the changes in
      some of the parameters that could be related to the above proposed causes of
      disease resurgence - vaccine effectiveness and effective transmission rates - may
      impact on pertussis transmission. When a linear decrease in vaccine effectiveness
      (VE) was assayed, a sustained increase in pertussis incidence was detected mainly
      in infants and children. On the other hand, when changes in effective
      transmission rates (betaij) were made, a dynamic effect evidenced by the presence
      of large peaks followed by deep valleys was detected. In this case, greater
      incidence in adolescents than in children was observed. These different trends in
      the disease dynamics due to modifications in VE or betaij were verified in 18
      possible scenarios that represent different epidemiological situations.
      Interestingly we found that both incidence trends produced by the model and their
      age distribution resemble the profiles obtained from data reported in several
      regions. The implications of these correlations are discussed. 

PMID- 24928666
TI  - Evaluating the potential impact of mass praziquantel administration for HIV
      prevention in Schistosoma haematobium high-risk communities.
AB  - Genital infection with Schistosoma haematobium is prevalent in sub-Saharan
      Africa. Epidemiological studies have observed that genital schistosomiasis is
      associated with an increased odd of HIV infection among women. We used
      mathematical modeling to explore the potential impact of mass preventive
      chemotherapy against schistosomiasis on HIV transmission in three sub-Saharan
      Africa countries: Angola, Kenya, and Zambia. We developed a model of female
      genital schistosomiasis (FGS) and HIV transmission dynamics, fitting it to data
      of HIV and S. haematobium prevalences as well as co-infection. We simulated
      targeted mass drug administration (MDA) with praziquantel to school-age children
      and mass treatment of the entire community. We estimated that, in S. haematobium
      high-risk communities, targeted annual treatment of school-age children could
      reduce HIV prevalence by 20% (95% CI: 12-31%) in Angola, 16% (95% CI: 10-32%) in
      Kenya, and 6% (95% CI: 3-18%) in Zambia after the first 20 years of intervention;
      and would reduce HIV incidence by 15% (95% CI: 13-32%) in Angola, 22% (95% CI: 18
      42%) in Kenya, and 9% (95% CI: 3-22%) in Zambia. Extending the intervention to
      adults could reduce HIV prevalence by an additional 2.2% (95% CI: 0.2-12.0%) in
      Angola, 1.8% (95% CI: 0.1-5.2%) in Kenya, and 0.3% (95% CI: 0.1-2.1%) in Zambia;
      and would reduce HIV incidence by an additional 1.8% (95% CI: 0.0-14.4%) in
      Angola, 6.1% (95% CI: 0.5-12.6%) in Kenya, and 0.8% (95% CI: 0.0-2.7%) in Zambia.
      We showed that the exacerbation of HIV transmission due to FGS and the
      probability of developing FGS as a result of childhood infection with S.
      haematobium, were the most important factors in determining the effectiveness of
      praziquantel MDA for reducing HIV transmission. Praziquantel MDA may be an
      innovative measure for reducing schistosomiasis and HIV transmission in sub
      Saharan Africa, the effectiveness of which varies with HIV prevalence. 

PMID- 24928667
TI  - OutbreakTools: a new platform for disease outbreak analysis using the R software.
AB  - The investigation of infectious disease outbreaks relies on the analysis of
      increasingly complex and diverse data, which offer new prospects for gaining
      insights into disease transmission processes and informing public health
      policies. However, the potential of such data can only be harnessed using a
      number of different, complementary approaches and tools, and a unified platform
      for the analysis of disease outbreaks is still lacking. In this paper, we present
      the new R package OutbreakTools, which aims to provide a basis for outbreak data
      management and analysis in R. OutbreakTools is developed by a community of
      epidemiologists, statisticians, modellers and bioinformaticians, and implements
      classes and methods for storing, handling and visualizing outbreak data. It
      includes real and simulated outbreak datasets. Together with a number of tools
      for infectious disease epidemiology recently made available in R, OutbreakTools
      contributes to the emergence of a new, free and open-source platform for the
      analysis of disease outbreaks. 

PMID- 24928668
TI  - Fabrication of an rhBMP-2 loaded porous beta-TCP microsphere-hyaluronic acid
      based powder gel composite and evaluation of implant osseointegration.
AB  - Methods to improve osseointegration that include implantation of rhBMP-2 with
      various kinds of carriers are currently of considerable interest. The present
      study was conducted to evaluate if the rhBMP-2 loaded beta-TCP microsphere
      hyaluronic acid-based powder-like hydrogel composite (powder gel) can act as an
      effective rhBMP-2 carrier for implantation in host bone with a bone defect or
      poor bone quality. The release pattern for rhBMP-2 was then evaluated against an
      rhBMP-2-loaded collagen sponge as a control group. Dental implants were also
      inserted into the tibias of three groups of rabbits: an rhBMP-2 (200 ug) loaded
      powder gel composite implanted group, an implant only group, and a powder gel
      implanted group. Micro-CT and histology of the implanted areas were carried out
      four weeks later. The rhBMP-2 powder gel released less rhBMP-2 than the collagen
      sponge, but it continued a slow release for more than 7 days. The rhBMP-2 powder
      gel composite improved osseointegration of the dental implant by increasing the
      amount of new bone formation in the implant pitch and it improved the bone
      quality and bone quantity of new bone. The histology results indicated that the
      rhBMP-2 powder gel composite improved the osseointegration in the cortical bone
      as well as the marrow space along the fixture. The bone-to-implant contact ratio
      of the rhBMP-2 (200 ug) loaded powder gel composite implanted group was
      significantly higher than those of the implant only group and the powder gel
      implanted group. The powder gel appeared to be a good carrier and could release
      rhBMP-2 slowly to promote the formation of new bone following implantation in a
      bone defect, thereby improving implant osseointegration. 

PMID- 24928669
TI  - Porous NiTi shape memory alloys produced by SHS: microstructure and
      biocompatibility in comparison with Ti2Ni and TiNi3.
AB  - Shape memory alloys based on NiTi have found their main applications in
      manufacturing of new biomedical devices mainly in surgery tools, stents and
      orthopedics. Porous NiTi can exhibit an engineering elastic modulus comparable to
      that of cortical bone (12-17 GPa). This condition, combined with proper pore
      size, allows good osteointegration. Open cells porous NiTi was produced by self
      propagating high temperature synthesis (SHS), starting from Ni and Ti mixed
      powders. The main NiTi phase is formed during SHS together with other Ni-Ti
      compounds. The biocompatibility of such material was investigated by single
      culture experiment and ionic release on small specimen. In particular, NiTi and
      porous NiTi were evaluated together with elemental Ti and Ni reference metals and
      the two intermetallic TiNi3, Ti2Ni phases. This approach permitted to clearly
      identify the influence of secondary phases in porous NiTi materials and relation
      with Ni-ion release. The results indicated, apart the well-known high toxicity of
      Ni, also toxicity of TiNi3, whilst phases with higher Ti content showed high
      biocompatibility. A slightly reduced biocompatibility of porous NiTi was ascribed
      to combined effect of TiNi3 presence and topography that requires higher effort
      for the cells to adapt to the surface.

PMID- 24928670
TI  - Lessons learned from the first fully magnetically levitated centrifugal LVAD
      trial in the United States: the DuraHeart trial.
AB  - BACKGROUND: The DuraHeart is a continuous centrifugal-flow left ventricular
      assist device that uses active magnetic levitation for impeller positioning
      designed for improved hemocompatibility and durability. This study reviews the
      results of the US trial with specific attention to hemolysis, thrombotic
      complications, and pump failure. METHODS: The US SUSTAIN trial was a multicenter,
      prospective, single-arm observational study in advanced heart failure patients
      listed for transplantation. Follow-up was complete in 100% of the patients at 6
      months. RESULTS: Sixty-three patients were enrolled at 23 centers. Forty-six
      patients (73%) reached the primary end points of survival to transplantation,
      alive on the original device at 180 days and listed for transplantation, or
      explant for recovery. Median duration of support was 267 days (range, 10 to 952
      days) with a total support time of 46 patient-years. There was no clinical
      hemolysis reported during the study. Mean lactate dehydrogenase values peaked at
      day 4 and significantly decreased during support (435+/-236 U/L and 297+/-142 U/L
      on day 3 and day 180, respectively). There were no cases of pump thrombosis
      reported, and 3 cases of pump thrombus "in transit" (0.06 events/patient-year)
      were observed. There were 6 (10%) cases of magnetic levitation system failure,
      all secondary to cable wire fractures (0.12 events/patient-year). All patients
      were hemodynamically stable with the backup hydrodynamic mode. Major adverse
      events included gastrointestinal bleeding (0.52 events/patient-year), ischemic
      and hemorrhagic strokes (0.17 events/patient-year and 0.09 events/patient-year,
      respectively), and driveline infections (0.67 events/patient-year). CONCLUSIONS:
      The DuraHeart demonstrated good hemocompatibility; however, the reliability of
      full magnetic levitation systems should be a high priority in future pump
      designs.

PMID- 24928671
TI  - Cancer stem cell phenotype is supported by secretory phospholipase A2 in human
      lung cancer cells.
AB  - BACKGROUND: Lung cancer stem cells (CSCs) are a subpopulation of cells that drive
      growth, invasiveness, and resistance to therapy. Inflammatory eicosanoids are
      critical to maintain this malignant subpopulation. Secretory phospholipase A2
      group IIa (sPLA2) is an important mediator of the growth and invasive potential
      of human lung cancer cells and regulates eicosanoid production. We hypothesized
      that sPLA2 plays a role in the maintenance of lung CSCs. METHODS: Cancer stem
      cells from lung adenocarcinoma cell lines H125 and A549 were isolated using
      aldehyde dehydrogenase activity and flow cytometry. Protein and mRNA levels for
      sPLA2 were compared between sorted cells using Western blotting and quantitative
      reverse transcriptase-polymerase chain reaction techniques. Chemical inhibition
      of sPLA2 and short-hairpin RNA knockdown of sPLA2 were used to evaluate effects
      on tumorsphere formation. RESULTS: Lung CSCs were isolated in 8.9%+/-4.1% (mean+/
      SD) and 4.1%+/-1.6% of H125 and A549 cells respectively. Both sPLA2 protein and
      mRNA expression were significantly elevated in the CSC subpopulation of H125
      (p=0.002) and A549 (p=0.005; n=4). Knockdown of sPLA2 significantly reduced
      tumorsphere formation in H125 (p=0.026) and A549 (p=0.001; n=3). Chemical
      inhibition of sPLA2 resulted in dose-dependent reduction in tumorsphere formation
      in H125 (p=0.003) and A549 (p=0.076; n=3). CONCLUSIONS: Lung CSCs express higher
      levels of sPLA2 than the non-stem cell population. Our findings that viral
      knockdown and chemical inhibition of sPLA2 reduce tumorsphere formation in lung
      cancer cells demonstrate for the first time that sPLA2 plays an important role in
      CSCs. These findings suggest that sPLA2 may be an important therapeutic target
      for human lung cancer.

PMID- 24928672
TI  - Lung resection improves the quality of life of patients with symptomatic
      bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is a significant cause of morbidity. Surgical
      resection is a treatment option, but its main outcomes regarding quality of life
      (QOL) and physiologic consequences have not been addressed previously, to our
      knowledge. We aimed to evaluate the effect of surgical procedures on QOL,
      exercise capacity, and lung function in patients with bronchiectasis in whom
      medical treatment was unsuccessful. METHODS: Patients with noncystic fibrosis in
      whom medical treatment was unsuccessful and who were candidates for lung
      resection were enrolled in a prospective study. The main measurements before lung
      resection and 9 months afterward were QOL according to the Short Form 36 Health
      Survey and World Health Organization Quality of Life Questionnaires, lung
      function test results, and the results of maximal cardiopulmonary exercise
      testing on a cycle ergometer. RESULTS: Of 61 patients who were evaluated, 53
      (50.9% male, age 41.3 +/- 12.9 years) underwent surgical resection (83%
      lobectomies), and 44 completed the 9-month follow-up. At baseline, they had low
      QOL scores, mild obstruction, and diminished exercise capacity. After resection,
      2 patients died and adverse events occurred in 24.5%. QOL scores improved
      remarkably at the 9-month measurements, achieving values considered normal for
      the general population in most dimensions. Functionally, resection caused mild
      reduction of lung volume; nevertheless, exercise capacity was not decreased. In
      fact, 52% of the patients improved their exercise performance. Multiple linear
      regression analysis showed that low QOL before resection was an important
      predictor of QOL improvement after resection (p = 0.0001). CONCLUSIONS: Lung
      resection promotes a significant improvement in the QOL of patients with
      noncystic fibrosis bronchiectasis without compromising their exercise capacity.

PMID- 24928673
TI  - Aortic arch advancement for aortic coarctation and hypoplastic aortic arch in
      neonates and infants.
AB  - BACKGROUND: The optimal treatment for infants with aortic coarctation and
      hypoplastic aortic arch is controversial. The goal of this study was to report
      the short-term and mid-term outcomes of aortic arch advancement (AAA) in infants
      with hypoplastic aortic arch. METHODS: All infants who underwent AAA at our
      institution from 1995 to 2012 were included. AAA consisted of coarctectomy and
      end-to-side anastomosis of the descending aorta to the distal ascending
      aorta/proximal arch through a median sternotomy. The cohort was divided into four
      groups: (1) isolated AAA (n=29, 11%), (2) AAA with closure of ventricular septal
      defect (n=56, 20%), (3) AAA with other biventricular repairs (n=115, 42%), and
      (4) AAA as part of single-ventricle palliation (n=75, 27%). RESULTS: The cohort
      included 275 patients: 125 (45%) were female, and the median age was 14 days
      (interquartile range, 7-34 days). Genetic abnormalities were present in 48
      patients (17%). Neurologic adverse events occurred in 3 patients (1%), all in
      group 4. Left bronchial compression was seen in 2 patients (0.7%); only one
      required intervention. Vocal cord dysfunction was noted in 36 of 95 patients
      (38%) on routine laryngoscopy. Only 1 patient had clinical residual dysfunction
      at the last follow-up visit. Perioperative mortality was 3% (n=8). At a median
      follow-up time of 6 years, 8 patients (3%) had reinterventions at a median time
      of 5 months (3-17 months) after repair. CONCLUSIONS: AAA is a safe, effective,
      and durable operation with low rates of adverse events and mid-term
      reintervention. The advantages include native tissue-to-tissue reconstruction and
      preserved potential for growth. As such, it is the ideal technique for the
      management of hypoplastic aortic arch in neonates and infants.

PMID- 24928674
TI  - Long-term results of neomedia sinus valsalva repair in 489 patients with type A
      aortic dissection.
AB  - BACKGROUND: Acute type A aortic dissection frequently occurs in patients with
      normally sized aortic roots. The aim of this investigation was to describe the
      durability of aortic valve resuspension and root repair with a novel technique of
      reconstruction in type A dissection. METHODS: From 1993 to 2013, among 629
      patients operated on for acute type A dissection 489 (62% male, median age 62
      years (53; 73) underwent aortic valve resuspension and reinforcement of the sinus
      of Valsalva with a Teflon felt neomedia. The median follow-up time was 4.1 years
      (1.3; 6.8) (2075 patient-years). RESULTS: In-hospital mortality was 11% (56/489).
      Survival was 69%+/-2%, 50%+/-3%, and 36%+/-5% at 5, 10, and 15 years,
      respectively. Freedom from moderate or severe aortic regurgitation was not
      influenced by the aortic regurgitation grade at the initial operation (p=0.131).
      Freedom from proximal aortic reoperation was 96%+/-1%, 92%+/-2%, and 89%+/-4% at
      5, 10, and 15 years, respectively. Seventeen patients (3%) required proximal
      reoperation: 10 for aortic regurgitation, including 3 with concomitant
      pseudoaneurysm and 2 with root aneurysm; 6 for pseudoaneurysm; and 1 for graft
      infection. CONCLUSIONS: Aortic root neomedia reconstruction and valve
      resuspension can be successfully performed in the majority of patients with type
      A dissection. The in-hospital mortality is low, and the results are durable.

PMID- 24928675
TI  - Does mitral valve repair offer an advantage over replacement in patients
      undergoing aortic valve replacement?
AB  - BACKGROUND: Concomitant aortic and mitral valve (MV) operations have more than
      doubled over the past decade. We utilized the Society of Thoracic Surgeons Adult
      Cardiac Surgery Database (ACSD) to evaluate outcomes for patients undergoing
      combined aortic valve replacement (AVR) and MV repair or replacement. METHODS:
      From 1993 to 2007, 23,404 patients undergoing concomitant AVR+MV surgery were
      identified. Patients with mitral stenosis, emergent or salvage status, and
      endocarditis were excluded. Outcomes were expressed as unadjusted operative
      mortality, adjusted odds ratio (OR) for mortality, and a composite of mortality
      and major complications. RESULTS: The MV repair was performed in 46.0% and
      replacement in 54.0% of AVR patients. The rate of MV repair increased from 22.5%
      in 1993 to 59.1% in 2007 (p<0.0001). Compared with the AVR+MV replacement group,
      the AVR+MV repair group was older (69.7+/-11.5 vs 67.2+/-12.7 years, p<0.0001),
      had worse ejection fraction (0.449+/-0.153 vs 0.495+/-0.139, p<0.0001), and more
      concomitant coronary artery bypass grafting (CABG) (50.5% vs 40.9%, p<0.0001).
      Unadjusted operative mortality was lower in the AVR+MV repair group (8.2% vs
      11.6%, p<0.0001). Predictors of operative mortality by multivariable analysis
      included the following: age (OR 1.21, p<0.0001); concomitant CABG (OR 1.49,
      p<0.0001); diabetes mellitus (OR 1.56, p<0.0001); reoperation (OR 1.53,
      p<0.0001); and renal failure with dialysis (OR 3.57, p<0.0001). Patients
      undergoing MV repair had a lower independent risk of operative mortality (OR
      0.61, p<0.0001), and mortality also independently improved over time (2003 to
      2007 vs 1993 to 1997, OR 0.79, p<0.002). CONCLUSIONS: When feasible, MV repair
      remains the most optimal method of correcting mitral regurgitation during
      concomitant AVR. Continued efforts to improve MV repair rates in this setting
      seem warranted.

PMID- 24928676
TI  - Thoracoscopic or open surgery for pulmonary metastasectomy: an observer blinded
      study.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) resection of pulmonary
      metastases has long been questioned because radiologically undetected parenchymal
      lesions may be missed when bimanual palpation is restricted to the portholes.
      Technology, however, has improved and advanced VATS resections are now performed
      routinely worldwide. This prompted us to conduct a prospective observer-blinded
      study on pulmonary metastasectomy. METHODS: Eligible patients with
      oligometastatic pulmonary disease on computed tomography (CT) underwent high
      definition VATS, with digital palpation by 1 surgical team and subsequent
      immediate thoracotomy during the same anesthesia by a different surgical team,
      with bimanual palpation and resection of all palpable nodules. Preoperative CT
      evaluations and surgical results were blinded. Primary endpoints were number and
      histopathology of detected nodules. RESULTS: During a 3-year period 89
      consecutive patients, with newly developed nodules suspicious of lung metastases
      from previous cancers in colon-rectum (n=59), kidney (n=15), and other
      malignancies (n=15) were included, with a total of 140 suspicious nodules visible
      on CT. During VATS, 122 nodules were palpable (87%). All nodules were identified
      during thoracotomy, where 67 additional and unexpected nodules were also
      identified; 22 were metastases (33%), 43 (64%) were benign lesions, and 2 (3%)
      were primary lung cancers. CONCLUSIONS: In patients operated for nodules
      suspicious of lung metastases, a substantial number of additional nodules were
      detected during thoracotomy despite advancements in CT imaging and VATS
      technology. Many of these nodules were malignant and would have been missed if
      VATS was used exclusively. Consequently, we considered VATS inadequate if the
      intention is to resect all pulmonary metastases during surgery.

PMID- 24928677
TI  - Women with malignant pleural mesothelioma have a threefold better survival rate
      than men.
AB  - BACKGROUND: Many studies have reported that women with malignant pleural
      mesothelioma (MPM) experience longer survival compared with men, whereas others
      have not. To date, no large population-based studies have evaluated MPM outcome
      and its determinants in female patients. METHODS: All pathologically confirmed
      cases of MPM in the Surveillance, Epidemiology and End Results database from 1973
      to 2009 were evaluated. Age, year of diagnosis, race, stage, cancer-directed
      surgery, radiation, and vital status were analyzed according to gender. Cox
      proportional hazard models were derived to assess the association between
      prognostic factors and survival. RESULTS: There were 14,228 cases of MPM, of
      which 3,196 (22%) were women. Despite similar baseline characteristics for both
      genders, 5-year survival was 13.4% in women and 4.5% in men (p < 0.0001). The
      effect of female gender on survival persisted when stratified by age
      (dichotomized at 50 years), stage, or race, but differed depending on treatment.
      Even when adjusted for age, stage, race, and treatment, female MPM patients
      experienced longer survival than men (hazard ratio = 0.78; 95% confidence
      interval 0.75 to 0.82). CONCLUSIONS: This large data set confirms that although
      MPM is less common in women, they present with similar stage and are offered
      similar treatment options compared with men. Nevertheless, survival is far better
      in women compared with men, independent of confounders such as age, stage, and
      treatment. Differences in asbestos exposure, tumor biology, and the impact of
      circulating hormones on host response must be investigated to understand this
      survival advantage and improve prognosis for patients of both genders.

PMID- 24928678
TI  - Better short-term outcome by using sutureless valves: a propensity-matched score
      analysis.
AB  - BACKGROUND: Sutureless aortic valve prostheses have the potential of shortening
      ischemic time. However, whether shorter operative times may also result in
      improved patient outcomes and have an effect on hospital costs remains to be
      established. METHODS: From March 2010 to April 2013, 566 patients underwent
      aortic valve replacement with bioprostheses; of these, 166 received a sutureless
      valve, and 400 received a stented valve. Redo and associated procedures were
      included. A propensity-score analysis was used to create two groups (sutureless
      and stented) with 82 matched pairs with comparable preoperative characteristics.
      Hospital outcome, follow-up, and health care resource consumption were compared.
      RESULTS: There were 3 hospital deaths in the stented group and 2 in the
      sutureless group (p=0.65). Aortic cross-clamp, cardiopulmonary bypass, and
      operation times were significantly shorter in the sutureless group (p<0.001).
      Patients in the sutureless group required blood transfusion less frequently
      (1.2+/-1.3 vs 2.5+/-3.7 units, p=0.005), with a similar need for reexploration
      for bleeding (2 vs 5, p=0.221). The sutureless group had a shorter intensive care
      unit stay (2.0+/-1.2 vs 2.8+/-1.3 days, p<0.001), hospital stay (10.9+/-2.7 vs
      12.4+/-4.4 days, p=0.001) and intubation time (9.5+/-4.6 vs 16.6+/-6.4 hours,
      p<0.001), and a lower incidence of postoperative atrial fibrillation (p=0.015),
      pleura effusions (p=0.024), and respiratory insufficiency (p=0.016). Pacemaker
      implantation and occurrence of neurologic events were similar between groups
      (p>0.05). A lower rate of postoperative complications resulted in reduced
      resource consumption in the sutureless group for diagnostics (?2,153 vs ?1,387),
      operating room (?5,879 vs ?5,527), and hospital stay (?9,873 vs ?6,584), with a
      total cost saving of approximately 25% (?17,905 vs ?13,498). CONCLUSIONS: A
      shorter procedural time in the sutureless group is associated with better
      clinical outcomes and reduced hospital costs.

PMID- 24928679
TI  - Nuclear calcium transients: Hermes Propylaios in the heart.

PMID- 24928681
TI  - Myocardial contractile dysfunction is associated with impaired mitochondrial
      function and dynamics in type 2 diabetic but not in obese patients.
AB  - BACKGROUND: Obesity and diabetes mellitus are independently associated with the
      development of heart failure. In this study, we determined the respective effects
      of obesity, insulin resistance, and diabetes mellitus on the intrinsic
      contraction and mitochondrial function of the human myocardium before the onset
      of cardiomyopathy. METHODS AND RESULTS: Right atrial myocardium was obtained from
      141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex
      vivo isometric contraction, mitochondrial respiration and calcium retention
      capacity, and respiratory chain complex activities and oxidative stress status.
      Diabetes mellitus was associated with a pronounced impairment of intrinsic
      contraction, mitochondrial dysfunction, and increased myocardial oxidative
      stress, regardless of weight status. In contrast, obesity was associated with
      less pronounced contractile dysfunction without any significant perturbation of
      mitochondrial function or oxidative stress status. Tested as continuous
      variables, glycated hemoglobin A1C, but neither body mass index nor the insulin
      resistance index (homeostasis model assessment-insulin resistance), was
      independently associated with cardiac mitochondrial function. Furthermore,
      diabetes mellitus was associated with cardiac mitochondrial network fragmentation
      and significantly decreased expression of the mitochondrial fusion related
      protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin
      A1C. CONCLUSION: Worsening of intrinsic myocardial contraction in the transition
      from obesity to diabetes mellitus is likely related to worsening of cardiac
      mitochondrial function because impaired mitochondrial function and dynamics and
      contractile dysfunction are observed in diabetic patients but not in
      "metabolically healthy" obese patients at early stage in insulin resistance.

PMID- 24928680
TI  - Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling
      during the development of hypertrophy and heart failure.
AB  - BACKGROUND: A hallmark of heart failure is impaired cytoplasmic Ca(2+) handling
      of cardiomyocytes. It remains unknown whether specific alterations in nuclear
      Ca(2+) handling via altered excitation-transcription coupling contribute to the
      development and progression of heart failure. METHODS AND RESULTS: Using tissue
      and isolated cardiomyocytes from nonfailing and failing human hearts, as well as
      mouse and rabbit models of hypertrophy and heart failure, we provide compelling
      evidence for structural and functional changes of the nuclear envelope and
      nuclear Ca(2+) handling in cardiomyocytes as remodeling progresses. Increased
      nuclear size and less frequent intrusions of the nuclear envelope into the
      nuclear lumen indicated altered nuclear structure that could have functional
      consequences. In the (peri)nuclear compartment, there was also reduced expression
      of Ca(2+) pumps and ryanodine receptors, increased expression of inositol-1,4,5
      trisphosphate receptors, and differential orientation among these Ca(2+)
      transporters. These changes were associated with altered nucleoplasmic Ca(2+)
      handling in cardiomyocytes from hypertrophied and failing hearts, reflected as
      increased diastolic Ca(2+) levels with diminished and prolonged nuclear Ca(2+)
      transients and slowed intranuclear Ca(2+) diffusion. Altered nucleoplasmic Ca(2+)
      levels were translated to higher activation of nuclear Ca(2+)/calmodulin
      dependent protein kinase II and nuclear export of histone deacetylases.
      Importantly, the nuclear Ca(2+) alterations occurred early during hypertrophy and
      preceded the cytoplasmic Ca(2+) changes that are typical of heart failure.
      CONCLUSIONS: During cardiac remodeling, early changes of cardiomyocyte nuclei
      cause altered nuclear Ca(2+) signaling implicated in hypertrophic gene program
      activation. Normalization of nuclear Ca(2+) regulation may therefore be a novel
      therapeutic approach to prevent adverse cardiac remodeling.

PMID- 24928683
TI  - Complex association between alcohol consumption and myocardial infarction: always
      good for a new paradox.

PMID- 24928684
TI  - Expression analysis of BORIS during pluripotent, differentiated, cancerous,  and
      non-cancerous cell states.
AB  - BORIS/CTCFL is an 11 zinc finger protein, which is the paralog of CTCF, a
      ubiquitously expressed protein with diverse roles in gene expression and
      chromatin organization. Several studies have shown that the expression of BORIS
      is restricted to normal adult testis, pluripotent cells, and diverse cancer cell
      lines. Thus, it is known as a cancer-testis (CT) gene that has been hypothesized
      to exhibit oncogenic properties and to be involved in cancer cell proliferation.
      On the contrary, other reports have shown that its expression is more widespread
      and can be detected in differentiated and normal somatic cells; hence, it might
      have roles in general cellular functions. The present study was aimed to analyze
      the expression of BORIS in different cell states of pluripotent, differentiated,
      cancerous and non-cancerous.We found that the two cell states of pluripotency and
      differentiation are not accompanied with significant variations of BORIS
      expression. Furthermore, Boris transcripts were detected at approximately the
      same level in cancer and non-cancer cell lines. These findings suggest that, in
      contrast to some previous reports, the expression of mouse BORIS is not limited
      to only cancerous cells or pluripotent cell states.

PMID- 24928685
TI  - Really interesting new gene finger protein 121 is a novel Golgi-localized
      membrane  protein that regulates apoptosis.
AB  - Really interesting new gene (RING) finger proteins represent a large protein
      family in the human genome, and play crucial roles in physiological activities
      and cancer development. The biological functions of some RING finger proteins
      remain unknown. Here, we described the biological activity of a novel, human
      Golgi-localized RING finger protein 121 (RNF121), the function of which is, thus
      far, unknown. Unlike the endoplasmic reticulum-localized RNF121 in Caenorhabditis
      elegans, human RNF121 is predominantly localized to the Golgi apparatus. RNF121
      knockdown inhibited cell growth and induced apoptosis, which was accompanied by
      caspase-3 activation and the cleavage of poly (adenosine diphosphate-ribose)
      polymerase. Z-VAD-FMK, a pan-caspase inhibitor, inhibited the RNF121
      knockdowninduced apoptosis. Over-expression of wild-type RNF121, but not the RING
      domain mutants of RNF121, decreased RNF121 knockdown-induced apoptosis,
      indicating that the RING domain is required for RNF121-regulated apoptosis.
      Moreover, RNF121 knockdown enhanced etoposide-induced apoptosis. This is the
      first study to demonstrate that RNF121 is a novel regulator of apoptosis and
      provides a new potential target for cancer therapy.

PMID- 24928686
TI  - Local infusion of citalopram into the basolateral amygdala decreased conditioned
      fear of rats through increasing extracellular serotonin levels.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment
      of depressive disorders and anxiety disorders. The anxiolytic mechanism of SSRIs
      is currently unclear. To investigate the anxiolytic effects of SSRIs, we measured
      both freezing behavior and extracellular serotonin and dopamine levels in the
      basolateral amygdala when rats were given conditioned fear stress under local
      reverse-dialysis of citalopram, an SSRI, into the basolateral amygdala. Local
      administration of citalopram into the basolateral amygdala significantly
      decreased freezing behavior induced by conditioned fear stress, and serotonin
      levels were simultaneously found to be significantly higher. Furthermore,
      repeated conditioned fear stress under local infusion of citalopram into the
      basolateral amygdala induced further increases in extracellular dopamine levels.
      Further studies investigating the role of dopamine in the amygdala for
      conditioned fear stress will be necessary. These results suggest that the
      basolateral amygdala is one of the target areas of the anxiolytic effects of
      citalopram and the increases of extracellular serotonin levels in the basolateral
      amygdala may be related to the anxiolytic effects. 

PMID- 24928687
TI  - Tyrosine phosphorylation profiling via in situ proximity ligation assay.
AB  - BACKGROUND: Tyrosine phosphorylation (pTyr) is an important cancer relevant
      posttranslational modification since it regulates protein activity and cellular
      localization. By controlling cell growth and differentiation it plays an
      important role in tumor development. This paper describes a novel approach for
      detection and visualization of a panel of pTyr proteins in tumors using in situ
      proximity ligation assay. METHODS: K562 leukemia cells were treated with tyrosine
      kinase and/or phosphatase inhibitors to induce differences in pTyr levels and
      mimic cells with different malignant properties. Cells were then probed with one
      antibody against the pTyr modification and another probe against the detected
      protein, resulting in a detectable fluorescent signal once the probes were in
      proximity. RESULTS: Total and protein specific pTyr levels on ABL, SHC, ERK2 and
      PI3K proteins were detected and samples of control and treated cells were
      distinguished at the pTyr level using this novel approach. Promising results were
      also detected for formalin fixed and paraffin embedded cells in the micro array
      format. CONCLUSIONS: This application of in situ proximity ligation assay is
      valuable in order to study the pTyr modification of a panel of proteins in large
      data sets to validate mass spectrometric data and to be combined with tissue
      microarrays. The approach offers new opportunities to reveal the pTyr signatures
      in cells of different malignant properties that can be used as biomarker of
      disease in the future.

PMID- 24928688
TI  - Analysis of biologically active oxyprenylated ferulic acid derivatives in Citrus
      fruits.
AB  - 4'-Geranyloxyferulic (GOFA) and boropinic acid have been discovered during the
      last decade as interesting phytochemicals having valuable pharmacological effects
      as cancer chemopreventive, anti-inflammatory, neuroprotective, and anti
      Helicobacter pylori agents. A reverse-phase HPLC-UV/Vis method for the separation
      and quantification of the title oxyprenylated ferulic acid derivatives in
      extracts obtained from peels of nine edible Citrus and Fortunella fruits was
      successfully applied. Concentration values showed a great variation between the
      different species, being orange (C. sinensis) the fruit richest in GOFA (0.141 +/
      0.011 mg/g of exocarp fresh weight) and kumquat (Fortunella japonica) the one in
      which boropinic acid was recorded as the most abundant phytochemical (0.206 +/-
      0.002 mg/g of exocarp fresh weight). Both secondary metabolites were not detected
      only in three species. The set-up methodology showed limits of quantification
      (LOQ) values, that were able to selectively quantify both GOFA and boropinic
      acid. Results described herein depict a potential chemopreventive dietary feeding
      role for the Rutaceae spp. under investigation.

PMID- 24928690
TI  - A time-resolved fluoroimmunoassay for the quantitation of rabies virus
      nucleoprotein in the rabies vaccine.
AB  - Sensitive, precise and rapid detection tests are needed in the quality control of
      rabies vaccine for rabies virus nucleoprotein. Previous studies for quantitation
      of rabies virus nucleoprotein focused on enzyme-linked immunosorbent assay
      (ELISA). A novel immunoassay for rapid determination of rabies virus
      nucleoprotein in rabies vaccine was first established by time-resolved
      fluoroimmunoassay (TRFIA). Based on a sandwich-type immunoassay format, analytes
      in samples were captured by one monoclonal antibody coating in the wells and
      "sandwiched" by another monoclonal antibody labeled with europium chelates. The
      immunocomplex was retained after washing, and then adopted treatment with
      enhancement solution; fluorescence was then measured according to the number of
      europiumions dissociated. Levels of the rabies virus nucleoprotein were measured
      in a linear range (5-2500 mEU/mL) with a lower limit of quantitation (0.95
      mEU/mL) under optimal conditions. The repeatability, recovery, and linearity of
      the immunoassay were demonstrated to be acceptable. The correlation coefficient
      of nucleoprotein values obtained by novel TRFIA method and ELISA method was
      0.981. These results showed good correlation and confirmed that this sensitive,
      precise and rapid TRFIA was feasible and could be more suitable for the quality
      control in the process of rabies vaccine production than ELISA.

PMID- 24928691
TI  - Development of a multiplex TaqMan probe-based real-time PCR for discrimination of
      variant and classical porcine epidemic diarrhea virus.
AB  - Since October 2010, porcine diarrhea outbreaks have occurred widely, resulting in
      major losses in suckling piglets in China. A variant porcine epidemic diarrhea
      virus (PEDV), characterized by base deletion and insertion in the S gene,
      compared to classical PEDV CV777, was shown to be responsible for this outbreak.
      In this study, a multiplex TaqMan probe-based real-time PCR was developed for
      detecting PEDV and differentiating the variant from classical PEDV, by using two
      sets of primers and probes based on the S gene of PEDV. The limits of detection
      of both variant and classical PEDV were 5*10(2) DNA copies. Specificity was
      determined using eight other viral pathogens of swine. Reproducibility was
      evaluated using standard dilutions, with coefficients of variation <1.4%.
      Standard dilutions included in each test allowed quantification of the amount of
      PEDV. Among 42 intestinal samples from pigs with severe watery diarrhea, 36
      variant PEDV and three classical PEDV samples were detected, with viral loads of
      10(2)-10(8) copies/MUl and 10(3)-10(5) copies/MUl, respectively, which suggested
      that the variant PEDV was prevalent in China. The multiplex TaqMan probe-based
      real-time PCR should be a useful tool for quantifying viral load, detecting PEDV,
      and differentiating variant from classical PEDV.

PMID- 24928692
TI  - Herpesvirus delivery to the murine respiratory tract.
AB  - Herpesvirus transmission is sporadic, and infection may be asymptomatic or
      present only with secondary lesions after dissemination. Consequently host entry
      remains ill-understood. Experimental infections can be informative, but depend on
      inoculations that are inherently artificial and so need validation. Mice are a
      widely used experimental host. Alert mice inhale readily small (5 MUl) liquid
      volumes, and Indian ink, luciferase or radiolabel delivered thus distributed to
      the nasopharynx and oropharynx. Murid Herpesvirus-4 or Herpes simplex virus type
      1 delivered thus infected only the nose, arguing that host entry is nasal rather
      than oral. Marker or virus delivery to the lung depended on general anesthesia
      and a large inoculum volume (30 MUl), and so needs further validation of
      physiological relevance. While lungs could be infected at lower doses than the
      upper respiratory tract, tracking experiments showed that nasal inocula pass
      mostly into the oropharynx, even when restricted to 1 MUl. Thus, the relative
      inefficiency of experimental upper respiratory tract infection was attributable
      to limited liquid retention in this site. Nonetheless low volume intranasal
      delivery to alert mice provides a convenient way to model experimentally an
      apparently natural mode of herpesvirus host entry.

PMID- 24928694
TI  - The Australian Register of antiepileptic drugs in pregnancy: changes over time in
      the epileptic population.
AB  - The demographic characteristics, details of pregnancies, epilepsies, and
      treatment of 855 pregnant women with epilepsy enrolled in the Australian
      Antiepileptic Drugs in Pregnancy Register during 1999-2005 were compared with the
      corresponding data for the 801 women enrolled from 2006-2012. We estimate that
      the Register captures approximately 1 in 12 of all pregnancies in Australian
      women with epilepsy. A number of statistically significant changes were found,
      with nearly all explained by factors such as re-enrolment of women who had
      enrolled earlier pregnancies, changes in general population behaviour, altered
      attitudes to prescribing valproate and using it in lower doses, and the advent of
      newer antiepileptic drugs which have displaced the use of older agents. It
      appears that the Register has continued to capture a reasonably representative
      sample of pregnant Australian women with epilepsy as time has passed. 

PMID- 24928682
TI  - Patterns of alcohol consumption and myocardial infarction risk: observations from
      52 countries in the INTERHEART case-control study.
AB  - BACKGROUND: Although moderate alcohol use is associated with protection against
      myocardial infarction (MI), it is not known whether this effect is generalizable
      to populations worldwide. It is also uncertain whether differences in the pattern
      of alcohol use (and in particular heavy episodic consumption) between different
      regions negate any beneficial effect. METHODS AND RESULTS: We included 12 195
      cases of first MI and 15 583 age- and sex-matched controls from 52 countries.
      Current alcohol use was associated with a reduced risk of MI (compared with
      nonusers: adjusted odds ratio, 0.87; 95% confidence interval, 0.80-0.94;
      P=0.001); however, the strength of this association was not uniform across
      different regions (region-alcohol interaction P<0.001). Heavy episodic drinking
      (>=6 drinks) within the preceding 24 hours was associated with an increased risk
      of MI (odds ratio, 1.4; 95% confidence interval, 1.1-1.9; P=0.01). This risk was
      particularly elevated in older individuals (for age >65 years: odds ratio, 5.3;
      95% confidence interval, 1.6-18; P=0.008). CONCLUSIONS: In most participants, low
      levels of alcohol use are associated with a moderate reduction in the risk of MI;
      however, the strength of this association may not be uniform across different
      countries. An episode of heavy drinking is associated with an increased risk of
      acute MI in the subsequent 24 hours, particularly in older individuals.

PMID- 24928693
TI  - HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in
      the southeastern USA.
AB  - PURPOSE: For poorly understood reasons, invasive cervical cancer (ICC) incidence
      and mortality rates are higher in women of African descent. Oncogenic human
      papillomavirus (HPV) genotypes distribution may vary between European American
      (EA) and African-American (AA) women and may contribute to differences in ICC
      incidence. The current study aimed at disentangling differences in HPV
      distribution among AA and EA women. METHODS: Five-hundred and seventy-two women
      were enrolled at the time of colposcopic evaluation following an abnormal liquid
      based cytology screen. HPV infections were detected using HPV linear array, and
      chi-squared tests and linear regression models were used to compare HPV genotypes
      across racial/ethnic groups by CIN status. RESULTS: Of the 572 participants, 494
      (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and
      88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with
      multiple HPV genotypes. After adjusting for race, age, parity, income, oral
      contraception use, and current smoking, AAs were two times less likely to harbor
      HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered.
      This association remained unchanged when only women with CIN2/3 lesions were
      examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV
      genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33,
      35, 45, 58, and 68 were the most frequent ones detected in AAs. CONCLUSIONS: Our
      data suggest that while HPV 16/18 are the most common genotypes among EA women
      with CIN, AAs may harbor different genotypes.

PMID- 24928695
TI  - Headache with focal neurologic signs in children at the emergency department.
AB  - OBJECTIVE: To identify predictors of secondary headache in children consulting at
      the pediatric emergency department (ED) for headache with a focal neurologic
      deficit. STUDY DESIGN: In this prospective cohort study, we enrolled children
      aged 6-18 years presenting to the ED of a tertiary care hospital with moderate to
      severe headache and focal neurologic deficit. Enrollment took place between March
      2009 and February 2012. Children with a history of trauma, fever, or
      neurosurgical intervention were excluded from the study. The final diagnosis was
      made after 1 year of follow-up. Our primary aim was to identify any differences
      in the frequency of clinical signs between children with a final diagnosis of
      primary headache and those with a final diagnosis of secondary headache. RESULTS:
      Of the 101 patients included in the study, 66% received a final diagnosis of
      primary headache (94% migraine with aura), and 34% received a final diagnosis of
      secondary headache (76.5% focal epilepsy). On multivariate analysis, children
      with bilateral localization of pain had a higher likelihood (aOR, 8.6; 95% CI,
      3.2-23.2; P<.001) of having secondary headache. CONCLUSION: Among children
      presenting to the ED with focal neurologic deficits, a bilateral headache
      location was associated with higher odds of having a secondary cause of headache.
      Additional longitudinal studies are needed to investigate whether our data can
      aid management in the ED setting.

PMID- 24928696
TI  - The hand on the trigger needs precise aim.

PMID- 24928697
TI  - The impact of race on analgesia use among pediatric emergency department
      patients.
AB  - We studied the effect of race on analgesia use in potentially pain-related
      pediatric emergency department visits using the National Hospital Ambulatory
      Medical Care Survey (2005-2010). There were independent patient- and hospital
      level racial disparities when it came to the type of analgesia used, suggesting
      black children are treated differently even within hospitals with high numbers of
      black patients. 

PMID- 24928698
TI  - Acute kidney injury associated with high nephrotoxic medication exposure leads to
      chronic kidney disease after 6 months.
AB  - OBJECTIVE: To assess the development of chronic kidney disease (CKD) after high
      nephrotoxic medication exposure-associated acute kidney injury (NTMx-AKI) in
      hospitalized children. STUDY DESIGN: We performed a retrospective cohort study of
      children exposed to an aminoglycoside for >=3 days or >=3 nephrotoxic medications
      simultaneously for the development of CKD at 6 months. Follow-up data >6 months
      after acute kidney injury (AKI) were retrieved from electronic health records.
      Outcomes in children with NTMx-AKI were compared with patients of same age and
      primary service distribution who were exposed to nephrotoxic medications but did
      not develop AKI (controls). RESULTS: One hundred patients with NTMx-AKI were
      assessed (mean age of 9.3 +/- 6.9 years). Commonly involved services were bone
      marrow transplantation/oncology (59%), liver transplantation (13%), and pulmonary
      (13%). Pre-AKI estimated glomerular filtration rate (eGFR) was 119 +/- 14.5
      mL/min/1.73 m(2) (range 90-150 mL/min/1.73 m(2)). Mean discharge eGFR was 105.1
      +/- 27.1 mL/min/1.73 m(2). At 6 months after NTMx-AKI, eGFR (n = 77) was 113.8 +/
      30.6 mL/min/1.73 m(2). Sixteen (20.7%) had eGFR of 60-90, 2 (2.6%) had eGFR <60,
      and 9 (11.6%) had eGFR >150 mL/min/1.73 m(2) (hyperfiltration). Twenty-four
      (68.5%) of 35 patients who were assessed for proteinuria had a urine protein-to
      creatinine ratio >0.3 mg/mg, and 29 (37.6%) had hypertension. Twenty-six (33.7%)
      patients had CKD (proteinuria or eGFR <60 mL/min/1.73 m(2)). An additional 28
      (36.3%) were considered to be at risk for CKD with hypertension, eGFR between 60
      and 90 mL/min/1.73 m(2), or eGFR >150 mL/min/1.73 m(2). CKD, hypertension, and
      proteinuria were more common in the AKI cohort than in controls. CONCLUSIONS: Six
      months after NTMx-AKI, 70% of patients had evidence of residual kidney damage
      (reduced eGFR, hyperfiltration, proteinuria, or hypertension). Few underwent a
      complete evaluation for CKD. With studies showing an association between AKI and
      CKD, we suggest systematic comprehensive follow-up in children after NTMx-AKI.

PMID- 24928699
TI  - Heart failure in children: etiology and treatment.

PMID- 24928700
TI  - Reply: To PMID 23992672.

PMID- 24928702
TI  - A young infant with periorificial and acral dermatitis.

PMID- 24928701
TI  - Looking beyond brachial plexus palsy.

PMID- 24928703
TI  - Knowledge, attitudes, and practices related to pet contact by immunocompromised
      children with cancer and immunocompetent children with diabetes.
AB  - OBJECTIVE: To compare knowledge, attitudes, and risks related to pet contact in
      households with and without immunocompromised children. STUDY DESIGN: A
      questionnaire was distributed to parents of children diagnosed with cancer
      (immunocompromised; n=80) or diabetes (immunocompetent; n=251) receiving care at
      the Children's Hospital of Eastern Ontario. Information was collected on
      knowledge of pets as sources of disease, concerns regarding pet-derived
      pathogens, and pet ownership practices. Data were analyzed with multivariable
      logistic regression. RESULTS: The questionnaire was completed by 65% (214 of 331)
      of the individuals to whom it was given. Pet ownership was common; 45% of
      respondents had a household pet when their child was diagnosed, and many
      (households with a child with diabetes, 49%; households with a child with cancer,
      20%) acquired a new pet after diagnosis. Most households that obtained a new pet
      had acquired a pet considered high risk for infectious disease based on
      species/age (diabetes, 73%; cancer, 77%). Parents of children with cancer were
      more likely than parents of children with diabetes to recall being asked by a
      physician/staff member if they owned a pet (OR, 5.9) or to recall receiving
      zoonotic disease information (OR, 5.3), yet these interactions were reported
      uncommonly (diabetes, <=13%; cancer, <=48%). Greater knowledge of pet-associated
      pathogens was associated with recalled receipt of previous education on this
      topic (OR, 3.9). Pet exposure outside the home was reported frequently for
      children in non-pet-owning households (diabetes, 48%; cancer, 25%). CONCLUSION:
      Improved zoonotic disease education is needed for pet-owning and non-pet-owning
      households with immunocompromised children, with ongoing provision of information
      while the children are at increased risk of disease. Additional efforts from
      pediatric and veterinary healthcare professionals are required.

PMID- 24928704
TI  - Application of anatomy and HPTLC in characterizing species of Dioscorea
      (Dioscoreaceae).
AB  - The edible tubers from different species of Dioscorea are a major source of food
      and nutrition for millions of people. Some of the species are medicinally
      important but others are toxic. The genus consists of about 630 species of almost
      wholly dioecious plants, many of them poorly characterized. The taxonomy of
      Dioscorea is confusing and identification of the species is generally
      problematic. There are no adequate anatomical studies available for most of the
      species. This study is aimed to fill this gap and provides a detailed
      investigation of the anatomy and micro-morphology of the rhizomes and tubers of
      five different species of Dioscorea, namely D. balcanica, D. bulbifera, D.
      polystachya, D. rotundata and D. villosa. The primary features that can help in
      distinguishing the species include the nature of periderm, presence or absence of
      pericyclic sclereids, lignification in the phloem, types of calcium oxalate
      crystals and features of starch grains. The descriptions are supported with
      images of bright-field and scanning electron microscopy for better understanding
      of these species. The diagnostic key of anatomical features included in this
      paper can help distinguish the investigated species unambiguously. Additionally,
      HPTLC analyses of authentic and commercial samples of the five species are
      described. 

PMID- 24928705
TI  - Patient-reported outcomes for psoriasis patients with clear versus almost clear
      skin in the clinical setting.
AB  - BACKGROUND: There is little evidence to guide the establishment of treatment
      goals for moderate to severe psoriasis in the clinical setting. OBJECTIVE: We
      sought to compare Dermatology Life Quality Index scores and prescription topical
      medication use between patients with clear versus almost clear skin. METHODS:
      This was a multicenter cross-sectional study of 97 patients with clear skin and
      441 patients with almost clear skin receiving current systemic therapy or
      phototherapy for a primary indication of plaque psoriasis evaluated at 1 of 10 US
      outpatient dermatology sites participating in the Dermatology Clinical
      Effectiveness Research Network. RESULTS: In adjusted analyses, patients with
      clear versus almost clear skin were more likely to report no impact of psoriasis
      on quality of life (relative risk 1.60; 95% confidence interval 1.37-1.86).
      Patients with clear versus almost clear skin were also more likely to report no
      prescription topical medication use in the preceding week (relative risk 2.08;
      95% confidence interval 1.73-2.49). LIMITATIONS: Cross-sectional design prohibits
      longitudinal assessment of outcomes. CONCLUSIONS: Clinically important
      differences in quality of life and prescription topical medication use exist
      between patients with clear versus almost clear skin. Collectively, our results
      indicate that achievement of clear skin may be an important clinical distinction
      among patients with moderate to severe psoriasis.

PMID- 24928706
TI  - Etanercept therapy for toxic epidermal necrolysis.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially lethal
      drug reaction for which no standard treatment is available. OBJECTIVE: To
      describe a case series of patients with TEN treated with a single dose of
      etanercept. METHODS: We observed 10 consecutive patients with TEN. For each
      patient, we recorded the presence of comorbidities and all the drugs recently
      started (ie, in the last month). In all cases, 50 mg of etanercept was
      administered in a single subcutaneous injection. The clinical severity of disease
      was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using
      the probabilities of death linked to each level of SCORTEN score, we calculated
      the expected probability of death in our patients. Healing was defined as
      complete reepithelialization, and a time to healing curve was then obtained using
      the Kaplan-Meier method. RESULTS: All patients promptly responded to treatment,
      reaching complete reepithelialization without complications or side effects. The
      median time to healing was 8.5 days. LIMITATIONS: This is a small, uncontrolled
      case series. CONCLUSION: These preliminary results suggest the possibility that
      tumor necrosis factor-alfa may be an effective target for control of TEN, a
      dangerous skin condition for which no effective cure has yet been found.

PMID- 24928707
TI  - Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and
      reflectance confocal microscopy.
AB  - BACKGROUND: The current guidelines for the management of basal cell carcinoma
      (BCC) suggest a different therapeutic approach according to histopathologic
      subtype. Although dermatoscopic and confocal criteria of BCC have been
      investigated, no specific studies were performed to evaluate the distinct
      reflectance confocal microscopy (RCM) aspects of BCC subtypes. OBJECTIVES: To
      define the specific dermatoscopic and confocal criteria for delineating different
      BCC subtypes. METHODS: Dermatoscopic and confocal images of histopathologically
      confirmed BCCs were retrospectively evaluated for the presence of predefined
      criteria. Frequencies of dermatoscopic and confocal parameters are provided.
      Univariate and adjusted odds ratios were calculated. Discriminant analyses were
      performed to define the independent confocal criteria for distinct BCC subtypes.
      RESULTS: Eighty-eight BCCs were included. Dermatoscopically, superficial BCCs
      (n=44) were primarily typified by the presence of fine telangiectasia, multiple
      erosions, leaf-like structures, and revealed cords connected to the epidermis and
      epidermal streaming upon RCM. Nodular BCCs (n=22) featured the classic
      dermatoscopic features and well outlined large basaloid islands upon RCM.
      Infiltrative BCCs (n=22) featured structureless, shiny red areas, fine
      telangiectasia, and arborizing vessels on dermatoscopy and dark silhouettes upon
      RCM. LIMITATIONS: The retrospective design. CONCLUSION: Dermatoscopy and confocal
      microscopy can reliably classify different BCC subtypes.

PMID- 24928708
TI  - Noninvasive monitoring of basal cell carcinomas treated with systemic hedgehog
      inhibitors: pseudocysts as a sign of tumor regression.
AB  - BACKGROUND: Oral hedgehog inhibitors (HHIs) have shown significant efficacy in
      the treatment of basal cell carcinoma (BCC). The evaluation of tumor regression
      has been performed using clinical photography and radiographic scans. Noninvasive
      imaging techniques, such as reflectance confocal microscopy (RCM) and high
      definition optical coherence tomography (HD-OCT), have been shown to be valuable
      in detecting BCC in the skin. OBJECTIVE: We monitored HHI-treated BCC using RCM
      and HD-OCT in vivo and correlated morphologic changes seen on imaging to changes
      in traditional histopathology. METHODS: Six BCCs in 5 patients receiving HHIs
      (vismodegib or sonidegib) were examined by RCM and HD-OCT before and during
      treatment. Characteristic features were compared to histopathologic findings,
      including immunohistochemical analysis. RESULTS: Characteristic features of BCC
      in RCM and HD-OCT decreased or disappeared completely during HHI treatment. Half
      of the clinically complete responding tumors still featured tumor residue.
      Pseudocystic structures ("empty" tumor nests in imaging) and widespread fibrosis
      (coarse bright fibers) were new findings and could be confirmed by
      histopathology. LIMITATIONS: Our study was limited by the number of tumor samples
      and imaging timepoints. CONCLUSION: Using RCM and HD-OCT, HHI-induced regression
      of BCC can be visualized noninvasively in the skin. The formation of pseudocysts
      and fibrosis were characteristic signs of BCC response to HHIs.

PMID- 24928709
TI  - Self-reported pigmentary phenotypes and race are significant but incomplete
      predictors of Fitzpatrick skin phototype in an ethnically diverse population.
AB  - BACKGROUND: Fitzpatrick skin phototype (FSPT) is the most common method used to
      assess sunburn risk and is an independent predictor of skin cancer risk. Because
      of a conventional assumption that FSPT is predictable based on pigmentary
      phenotypes, physicians frequently estimate FSPT based on patient appearance.
      OBJECTIVE: We sought to determine the degree to which self-reported race and
      pigmentary phenotypes are predictive of FSPT in a large, ethnically diverse
      population. METHODS: A cross-sectional survey collected responses from 3386
      individuals regarding self-reported FSPT, pigmentary phenotypes, race, age, and
      sex. Univariate and multivariate logistic regression analyses were performed to
      determine variables that significantly predict FSPT. RESULTS: Race, sex, skin
      color, eye color, and hair color are significant but weak independent predictors
      of FSPT (P<.0001). A multivariate model constructed using all independent
      predictors of FSPT only accurately predicted FSPT to within 1 point on the
      Fitzpatrick scale with 92% accuracy (weighted kappa statistic 0.53). LIMITATIONS:
      Our study enriched for responses from ethnic minorities and does not fully
      represent the demographics of the US population. CONCLUSIONS: Patient self
      reported race and pigmentary phenotypes are inaccurate predictors of sun
      sensitivity as defined by FSPT. There are limitations to using patient-reported
      race and appearance in predicting individual sunburn risk.

PMID- 24928710
TI  - Risk factors for infections in international travelers: an analysis of travel
      related notifiable communicable diseases.
AB  - BACKGROUND: We sought to describe travel-related illness among our residents and
      gain insight into targeting pre-travel health advice to prevent travel-related
      illness. METHODS: A supplemental travel questionnaire was developed and
      administered for cases with a legally notifiable communicable disease reported in
      2011-2012, who spent at least part of their exposure period outside the United
      States. RESULTS: Among 451 cases meeting the eligibility criteria, 259 were
      interviewed. Forty four percent reported receiving pre-travel advice. Two-thirds
      adhered fully with risk behavior recommendations; 94% followed immunization
      recommendations partially or fully; and 84% adhered fully with malaria
      prophylaxis recommendations. The primary reasons for not obtaining pre-travel
      advice were being unaware of the need (47.5%), or believing they already knew
      what to do (34.5%). Adults (OR = 2.8, 95% CI = 1.4-5.5), males (OR = 1.8, 95% CI
      = 1.1-3.0), those born outside the United States (OR = 2.0, 95% CI = 1.1-3.7),
      and those with planning time under two weeks (OR = 4.8, 95% CI = 1.5-15.9) or
      travel duration less than 7 days (OR = 7.9, 95% CI = 3.0-20.9) were more likely
      to travel without seeking pre-travel advice. CONCLUSIONS: The majority of cases
      reported not receiving pre-travel advice. Understanding the predictors of failure
      to receive pre-travel advice may help target public health prevention efforts.

PMID- 24928711
TI  - Steroid-resistant acute rejection after cadaveric liver transplantation:
      experience from one single center.
AB  - BACKGROUND AND OBJECTIVES: Steroid-resistant acute rejection (SRAR) is an
      infrequent event under current immunosuppressant but still a risk factor leading
      to graft loss and patients' death after liver transplantation. There are several
      strategies for managing this complication according to current literatures, but
      none of the treatment seems convincing and widely accepted. Here we
      retrospectively analyzed the clinical data of a cohort of patients to gain an
      insight into this complication. MATERIALS AND METHODS: A total of 962 adult
      patients receiving whole liver grafts at a single center between January 2004 and
      December 2012 were studied. One hundred and forty-two recipients experienced 158
      episodes of acute rejection after the operation, 14 recipients had no response to
      steroid bolus treatment. The clinical data was analyzed retrospectively. RESULTS:
      Incidence rate of acute rejection after liver transplant in our single center was
      14.7% (142/962), among them 8.8% (14/158) were steroid-resistant. These episodes
      occurred on 19days (6-72days) after the operation, 3 were controlled by anti-T3
      receptor antibody (OKT3) treatment, 4 were reversed by IL-2 receptor inhibitors
      combining with MMF treatment, 2 were reversed by antithymocyte globulin (ATG)
      treatment. Five did not recover and 2 received retransplantation. Mortality
      associated with SRAR was 28.6% (4/14, 1 died from acute liver failure, 1 from
      chronic liver failure, 1 from renal failure after retransplantation and 1 from
      pulmonary infection after OKT3 treatment). CONCLUSION: SRAR is a severe
      complication with high mortality after liver transplantation; ATG might serve as
      a potential treatment.

PMID- 24928712
TI  - Concurrent variably protease-sensitive prionopathy and amyotrophic lateral
      sclerosis.

PMID- 24928713
TI  - Cisplatin administration influences on toxic and non-essential element metabolism
      in rats.
AB  - Nowadays several papers deal with the effectiveness and side effects of metal
      complexes, especially cisplatin, in cancer therapy. The excretion of essential
      metal elements from the body is a serious problem in the treatment, but there are
      no data concerning the distribution and metabolism of toxic and nonessential
      elements. Therefore our aim was to study the concentration of some of these
      elements after treatment with cisplatin. Male Wistar rats (n=20, 175-190 g) were
      randomly divided into 2 groups (n=10/group). The control group received 1% (w/v)
      methyl cellulose at 10 mL/kg body weight, p.o. by gastric gavage twice daily for
      14 days, while cisplatin was injected i.p. in a single dose of 6.5 mg/kg body
      weight. Inductively coupled plasma optical emission spectrometry (ICP-OES) was
      used for measuring Al, B, Ba, Cr, Li, Ni, Pb, Pt, Sb, Si, Sn, Sr and V content in
      plasma, liver and kidney. Liver total scavenger capacity, diene conjugate content
      and malondialdehyde concentration were also determined. Cisplatin elevated the
      free radical reactions in the liver, although redox balance did not change
      significantly. According to the study it seems that the metabolism of Al, Ba, Cr,
      Ni, Pb, Sr were changed by the effect of cisplatin, and the most notable
      alterations were found for Al and Pb. Therefore, besides the toxic effect of and
      free radical induction by Pt, the side effects of increased levels of other toxic
      and non-essential elements have to be taken into consideration.

PMID- 24928714
TI  - Musculoskeletal: what's different in children? Running hard: acute hip pain: two
      patients.

PMID- 24928715
TI  - Is morphology alone able to predict BRAF-mutated malignancies on thyroid FNAC?

PMID- 24928716
TI  - 4th Georgian Bay International Conference on Bioinorganic Chemistry.

PMID- 24928717
TI  - [Use of ineffective practices in Primary Health Care: professional opinions].
AB  - OBJECTIVE: To estimate the frequency of ineffective practices in Primary Health
      Care (PHC) based on the opinions of clinical professionals from the sector, and
      to assess the significance, implications and factors that may be contributing to
      their continuance. MATERIAL AND METHODS: An on line survey of opinion from a
      convenience sample of 575 professionals who had published articles over the last
      years in Atencion Primaria and Semergen medical journals. RESULTS: A total of 212
      professionals replied (37%). For 70.6% (95% confidence interval [CI] 64.5 to
      73.3) the problem of ineffective practices is frequent or very frequent in PHC,
      and rate their importance with an average score of 7.3 (standard deviation
      [SD]=1.8) out of 10. The main consequences would be endangering the
      sustainability of the system (48.1%; 95% CI, 41.2 to 54.9) and harming patients
      (32.1%; 95% CI, 25.7 to 38.5). These ineffective practices are the result of the
      behaviour of the patients themselves (28%; 95% CI, 22.6 to 35.0) workload (26.4%;
      95% CI, 20.3 to 32.5), and the lack of the continuous education (19.3%; 95% CI,
      13.9 to 24.7). Clinical procedures of greatest misuse are the prescribing of
      antibiotics for certain infections, the frequency of cervical cancer screening,
      rigorous pharmacological monitoring of type 2 diabetes in patients over 65 years,
      the use of psychotropic drugs in the elderly, or the use of analgesics in
      patients with hypertension or renal failure. CONCLUSIONS: The use of ineffective
      procedures in PHC is considered a very important issue that negatively affects
      many patients and their treatment, and possibly endangering the sustainability of
      the system and causing harm to patients.

PMID- 24928718
TI  - [Assessing patient satisfaction of family planning services in a rural area].

PMID- 24928719
TI  - [Early colorectal cancer detection programs: an integration and quality
      healthcare challenge].

PMID- 24928720
TI  - Can the Effects of Religion and Spirituality on Both Physical and Mental Health
      be Scientifically Measured? An Overview of the Key Sources, with Particular
      Reference to the Teachings of Said Nursi.
AB  - Within Western secular societies, everything has to be substantiated by empirical
      evidence; this means it has to be quantifiable and measurable. Research,
      particularly quantitative research, then, is the criterion by which everything,
      including religion, is either accepted or rejected. The separation of religion
      from science began with the Renaissance, the Reformation and the advent of the
      Enlightenment. It was perceived that religion did not match the language of
      science and that there was no logical proof or empirical evidence for the
      existence of God. Religion therefore, due to its inability to be measured and
      quantified, has since been largely marginalised. In recent times, in order to
      integrate 'religion' into everyday life, attempts have been made to argue and
      bring in scientific proof for the effectiveness of religion for improved health
      and well-being. The psychiatrist Harold Koenig has been one of the key people
      whose collation of research evidence has shown that religion has a positive
      effect on both physical and mental health. By looking firstly at the definitions
      of religion and spirituality and then discussing various opinions from both
      secular and religious perspectives, including those of Said Nursi, this paper
      aimed to determine whether religion and spirituality can indeed be measured. 

PMID- 24928721
TI  - The neuronal mineralocorticoid receptor: from cell survival to neurogenesis.
AB  - Mineralocorticoid receptor (MR), a hormone-activated transcription factor
      belonging to the nuclear receptor superfamily, exerts widespread actions in many
      tissues such as tight epithelia, the cardiovascular system, adipose tissues and
      macrophages. In the mammalian brain, MR is present in the limbic areas where it
      is highly expressed in neurons of the hippocampus and mostly absent in other
      regions while the glucocorticoid receptor (GR) expression is ubiquitous. MR binds
      both aldosterone and glucocorticoids, the latter having a ten-fold higher
      affinity for MR than for the closely related GR. However, owing to the minimal
      aldosterone transfer across the blood brain barrier and the absence of neuronal
      11beta hydroxysteroid dehydrogenase type 2 as an intracellular gate-keeper,
      neuronal MR appears to be fully occupied even at low physiological glucocorticoid
      levels while GR activation only occurs at high glucocorticoid concentrations,
      i.e. at the peak of the circadian rhythm or under stress. This defined a one
      hormone/two receptors system that works in balance, modulating a large spectrum
      of actions in the central nervous system. MR and GR are involved in the stress
      responses, the regulation of neuron excitability, long term potentiation,
      neuroprotection and neurogenesis in the dentate gyrus. MR thus constitutes a key
      factor in the arising of higher cognitive functions such as memorization,
      learning and mood. This review presents an overview of various roles of MR in the
      central nervous system which are somewhat less studied than that of GR, in the
      light of recent data obtained using cellular models, animal models and clinical
      investigations. 

PMID- 24928722
TI  - Regio- and stereoselective access to novel ring-condensed steroidal isoxazolines.
AB  - Novel 5alpha-androstanes containing an isoxazoline moiety condensed to ring A or
      D were efficiently synthetized by 1,3-dipolar cycloadditions of aryl nitrile
      oxides to steroidal alpha,beta-unsaturated ketones. During the ring closures,
      regioisomers in which the O terminus of the nitrile oxide dipoles is attached to
      the beta-carbon of the dipolarophile were formed in a stereoselective manner to
      furnish exclusively 1alpha,2alpha- or 15beta,16beta-condensed heterocycles. The
      cyclic enone moiety of the six-membered ring A proved to be less reactive than
      that of the five-membered ring D, but all the reactions were affected
      significantly by the substitution pattern of the nitrile oxide. 17-Deacetylation
      of the primary products resulted in aromatization or simultaneous hydroxylation,
      depending on the base applied for the ring A-fused heterocycles, while retro
      Dieckmann-like fragmentation was observed partially or completely for the ring D
      fused analogues during 3-deacetylation. 

PMID- 24928723
TI  - Use of endogenous cortisol 6beta-hydroxylation clearance for phenotyping in vivo
      CYP3A activity in women after sequential administration of an oral contraceptive
      (OC) containing ethinylestradiol and levonorgestrel as weak CYP3A inhibitors.
AB  - The present study was undertaken to evaluate the time courses of in vivo
      cytochrome P450 3A (CYP3A) inhibition in four healthy women after sequential
      administration of an oral contraceptive (OC) containing ethinylestradiol and
      levonorgestrel, using 6beta-hydroxylation clearance of endogenous cortisol
      (CLm(6beta)) as a new index for CYP3A phenotyping. The 6beta-hydroxylation
      clearance (CLm(6beta)) was followed every 2h from 9:00 or 11:00 to 17:00 on days
      0 (baseline), 1, 2, 21, and 28 during a single menstrual cycle. The serum
      concentrations of endogenous estradiol and progesterone were also measured. The
      time course data of CLm(6beta) clearly demonstrated 43-64% inhibition of CYP3A
      activity in women taking a low daily dose of the OC for 21days. The average
      CLm(6beta) levels that were suppressed by the OC in four women were extremely low
      (0.60-1.23mL/min) compared with the normal CLm(6beta) range (1.5-3.5mL/min) that
      was obtained from 49 healthy subjects in our previous study. The in vivo
      inhibitory potencies (43-64%) obtained in this study were stronger than expected
      from reported in vitro studies (~20%). Furthermore, it would take at least seven
      days to return to the baseline activity of CYP3A after discontinuation of the OC.
      The results presented here should provide important information on the inhibitory
      effect of OC on the CYP3A activities in women, which are involved in the
      metabolism of a number of drugs with a narrow therapeutic range. 

PMID- 24928724
TI  - Synthesis of steroidal derivatives containing substituted, fused and spiro
      pyrazolines.
AB  - An efficient and facile synthesis of fused, substituted and spiro pyrazoline
      steroid derivatives through a cycloaddition reaction of different alpha,beta
      unsaturated ketones with hydrazine acetate in acetic acid is reported. Depending
      on the starting material, the ring closure reaction provided a mixture of two
      steroidal pyrazoline epimers that were separated and studied by NMR techniques.
      In one case it was possible to isolate and characterize the hydrazone derivative
      as the reaction intermediate, which confirms the mechanism proposed in the
      literature [11,25,26]. 

PMID- 24928725
TI  - Transcriptional regulation of myotrophic actions by testosterone and trenbolone
      on androgen-responsive muscle.
AB  - Androgens regulate body composition and skeletal muscle mass in males, but the
      molecular mechanisms are not fully understood. Recently, we demonstrated that
      trenbolone (a potent synthetic testosterone analogue that is not a substrate for
      5-alpha reductase or for aromatase) induces myotrophic effects in skeletal muscle
      without causing prostate enlargement, which is in contrast to the known prostate
      enlarging effects of testosterone. These previous results suggest that the 5alpha
      reduction of testosterone is not required for myotrophic action. We now report
      differential gene expression in response to testosterone versus trenbolone in the
      highly androgen-sensitive levator ani/bulbocavernosus (LABC) muscle complex of
      the adult rat after 6weeks of orchiectomy (ORX), using real time PCR. The ORX
      induced expression of atrogenes (Muscle RING-finger protein-1 [MuRF1] and atrogin
      1) was suppressed by both androgens, with trenbolone producing a greater
      suppression of atrogin-1 mRNA compared to testosterone. Both androgens elevated
      expression of anabolic genes (insulin-like growth factor-1 and mechano-growth
      factor) after ORX. ORX-induced increases in expression of glucocorticoid receptor
      (GR) mRNA were suppressed by trenbolone treatment, but not testosterone. In ORX
      animals, testosterone promoted WNT1-inducible-signaling pathway protein 2 (WISP
      2) gene expression while trenbolone did not. Testosterone and trenbolone equally
      enhanced muscle regeneration as shown by increases in LABC mass and in protein
      expression of embryonic myosin by western blotting. In addition, testosterone
      increased WISP-2 protein levels. Together, these findings identify specific
      mechanisms by which testosterone and trenbolone may regulate skeletal muscle
      maintenance and growth. 

PMID- 24928726
TI  - Synthesis and antiproliferative activity of some steroidal thiosemicarbazones,
      semicarbazones and hydrozones.
AB  - Steroidal thiosemicarbazones, semicarbazones and hydrazones have received
      extensive attention of scientists recently because they exhibit some biological
      activities such as antibacterial, antiviral and anticancer. Using different
      steroids as starting materials, through different chemical methods, 24 steroidal
      compounds with thiosemicarbazone, semicarbazone or hydrazone groups in their
      structures, were synthesized, characterized by IR, NMR and MS. The
      antiproliferative activity of the compounds was evaluated against human gastric
      cancer (SGC-7901) and human liver cancer (Bel-7404) cells. The structure-activity
      relationship of these compounds was discussed. The results showed that compound 3
      and 12a-12c exhibited significant inhibitory activity to Bel-7404 cells, and IC50
      values of them were 4.2, 11.0, 7.4 and 15.0MUM respectively (Cisplatin, IC50:
      11.6MUM). 

PMID- 24928727
TI  - Syntheses and antiproliferative effects of D-homo- and D-secoestrones.
AB  - Substituted and/or heterocyclic d-homoestrone derivatives were synthetized via
      the intramolecular cyclization of a delta-alkenyl-d-secoaldehyde, -d-secoalcohol
      or -d-secocarboxylic acid of estrone 3-benzyl ether. The d-secoalcohol was
      modified at three sites in the molecule. The in vitro antiproliferative
      activities of the new d-homo- and d-secoestrone derivatives were determined on
      HeLa, MCF-7, A431 and A2780 cells through use of MTT assay. d-Homoalcohols 3 and
      5 displayed cell line-selective cytostatic effects against ovarian and cervical
      cell lines, respectively. Two d-secoestrones (6 and 12c) proved to be effective,
      with IC50 values comparable with those of the reference agent cisplatin. A
      selected compound (6) was tested by tubulin polymerization assay and its cancer
      specificity was additionally determined by using noncancerous human fibroblast
      cells. 

PMID- 24928728
TI  - Synthesis of novel vitamin D3 analog with an additional ring annulated to A and
      seco-B rings.
AB  - A simple method for the synthesis of yet unknown 5E-vitamin D3 analogs with an
      additional six-membered ring connecting C-6 and C-19 was developed. Ring-closing
      metathesis (RCM) was used for efficient formation thereof from the corresponding
      5E-isomers of 6-alkenyl vitamin D3 compounds which in turn were prepared from the
      6-oxo-3,5-cyclovitamin D3. Reinvestigation of the Grignard reactions of this
      latter compound as well as the following acid-catalyzed cycloreversions showed
      discrepancies with the literature data describing the course of such processes. 

PMID- 24928729
TI  - Mineralocorticoid receptor signaling: crosstalk with membrane receptors and other
      modulators.
AB  - The mineralocorticoid receptor (MR) belongs to the steroid receptor superfamily.
      Classically, it acts as a ligand-bound transcription factor in epithelial
      tissues, where it regulates water and electrolyte homeostasis and controls blood
      pressure. Additionally, the MR has been shown to elicit pathophysiological
      effects including inflammation, fibrosis and remodeling processes in the
      cardiovascular system and the kidneys and MR antagonists have proven beneficial
      for patients with certain cardiovascular and renal disease. The underlying
      molecular mechanisms that mediate MR effects have not been fully elucidated but
      very likely rely on interactions with other signaling pathways in addition to
      genomic actions at hormone response elements. In this review we will focus on
      interactions of MR signaling with different membrane receptors, namely receptor
      tyrosine kinases and the angiotensin II receptor because of their potential
      relevance for disease. In addition, GPR30 is discussed as a new aldosterone
      receptor. To gain insights into the problem why the MR only seems to mediate
      pathophysiological effects in the presence of additional permissive factors we
      will also briefly discuss factors that lead to modulation of MR activity as well.
      Overall, MR signaling is part of an intricate network that still needs to be
      investigated further. 

PMID- 24928730
TI  - The elevated level of ERalpha36 is correlated with nodal metastasis and poor
      prognosis in lung adenocarcinoma.
AB  - INTRODUCTION: ERalpha36 is a recently cloned variant of estrogen receptor-alpha
      which has been proved to play an active role in a series of malignant diseases.
      METHOD: ERalpha36 expression was examined using immunohistochemical methods with
      sections from 126 resected NSCLC specimens. The immunoreactivity of ERalpha66 was
      also studied as a comparison. Kaplan-Meier method and multivariable Cox
      proportional hazards regression analyses were used to examine the relationship
      between ERalpha36 and survival. RESULT: ERalpha36 was more highly expressed in
      NSCLC patients compared to ERalpha66. ERalpha36 expression has a strong
      correlation with histology (AC: 53/70, SCC: 16/56, P<0.000) and had a
      significantly positive correlation with lymphatic metastasis (P=0.014) in
      adenocarcinoma. High ERalpha36 expression was correlated with poorer overall
      survival (OS) (P=0.020) and disease-free survival (DFS) (P=0.024) in
      adenocarcinoma. Furthermore, ERalpha36 status was a significant independent
      prognostic factor of OS (P=0.018, HR: 3.142, 95% CI: 1.215-8.128) and DFS
      (P=0.024, HR: 2.720, 95% CI: 1.141-6.486) in lung adenocarcinoma patients.
      CONCLUSION: ERalpha36 had a high expression mainly in adenocarcinoma and the high
      expression of ERalpha36 was strongly correlated with more advanced regional lymph
      node metastasis and poor survival in lung adenocarcinoma.

PMID- 24928731
TI  - Discovery of novel steroidal pyran-oxindole hybrids as cytotoxic agents.
AB  - A series of novel steroidal pyran-oxindole hybrids were efficiently synthesized
      in a single operation through the vinylogous aldol reaction of vinyl
      malononitrile 3 with substituted isatins involving the construction of C-C and C
      O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC
      7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu
      against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45 MUM,
      respectively. Further mechanism studies indicated that compound 4i induced G2/M
      arrest and early apoptosis in a concentration- and time-dependent manner.

PMID- 24928732
TI  - Identification of cortisol metabolites in the bile of Atlantic cod Gadus morhua
      L.
AB  - Interpretation of plasma cortisol levels in wild-caught fish is confounded by the
      stress of capture. Measurement of cortisol metabolites in fish bile could provide
      a method for assessing the stress level of wild fish because the time-lag for
      metabolism, conjugation and excretion into bile avoids the effects of sampling
      stress. To determine which biliary metabolite(s) to target, four Atlantic cod,
      Gadus morhua L., were injected with radioactive cortisol. After 22 h, the bile
      was collected and found to contain 30% of the injected activity. Cortisol
      metabolites were extracted from diluted bile samples using solid phase extraction
      and the radioactive metabolites separated by several different chromatographic
      procedures. The metabolites were predominantly present as sulfates (95%) with the
      remainder being glucuronidated. Chromatography split the sulfates into at least
      seven peaks, and acid solvolysis (which removes sulfate groups from steroids)
      generated four major radioactive steroids. These were identified, using
      microchemical reactions and re-crystallization to constant specific activity, as:
      11beta,17,21-trihydroxypregn-4-ene-3,20-dione (cortisol), 3alpha,11beta,17,21
      tetrahydroxy-5beta-pregnan-20-one (tetrahydrocortisol; THF), 3alpha,17,21
      trihydroxy-5beta-pregnane-11,20-dione (tetrahydrocortisone; THE) and
      3alpha,17,20beta,21-tetrahydroxy-5beta-pregnan-11-one (beta-cortolone). The last
      of these was the most abundant, and thus a likely target for a biliary stress
      assay. Studies were also carried out to determine the best method for extraction
      and solvolysis of sulfates. Solid phase extraction (i.e. using octadecylsilane)
      was found to be too unreliable for routine use. Even though the extraction
      efficiency could be improved by acidifying the bile, this caused premature
      solvolysis of sulfated steroids. Acid solvolysis of unextracted bile worked best
      (c. 90% converted to free steroids) on volumes that were 1 MUL or lower. Aryl
      sulfatase digestion of unextracted bile did not work well (only 20% of
      radioactivity was converted to free steroids).

PMID- 24928733
TI  - Mental structures and hierarchical brain processing. Comment on "Toward a
      computational framework for cognitive biology: unifying approaches from cognitive
      neuroscience and comparative cognition" by W. Tecumseh Fitch.

PMID- 24928734
TI  - Insights into new bacteriophages of Lactococcus garvieae belonging to the family
      Podoviridae.
AB  - Lactococcus garvieae is an emerging pathogen responsible for lactococcosis, a
      serious disease in trout aquaculture. The identification of new bacteriophages
      against L. garvieae strains may be an effective way to fight this disease and to
      study the pathogen's biology. Three L. garvieae phages, termed WP-1, WWP-2 and SP
      2, were isolated from different environments, and their morphological features,
      genome restriction profiles and structural protein patterns were studied. Random
      cloning of HindIII-cut fragments was performed, and the fragments were partially
      sequenced for each phage. Although slight differences were observed by
      transmission electron microscopy, all of the phages had hexagonal heads and short
      non-contractile tails and were classified as members of the family Podoviridae.
      Restriction digestion analysis of the nucleic acids of the different phages
      revealed that the HindIII and AseI digests produced similar DNA fragment
      patterns. Additionally, SDS-PAGE analysis indicated that the isolated phages have
      similar structural proteins. The sequence BLAST results did not show any
      significant similarity with other previously identified phages. To the best of
      our knowledge, this study provides the first molecular characterization of L.
      garvieae phages. 

PMID- 24928736
TI  - ErbB/HER protein-tyrosine kinases: Structures and small molecule inhibitors.
AB  - The epidermal growth factor receptor (EGFR) family consists of four members that
      belong to the ErbB lineage of proteins (ErbB1-4). These receptors consist of an
      extracellular domain, a single hydrophobic transmembrane segment, and an
      intracellular portion with a juxtamembrane segment, a protein kinase domain, and
      a carboxyterminal tail. The ErbB proteins function as homo and heterodimers.
      Growth factor binding to EGFR induces a large conformational change in the
      extracellular domain. Two ligand-EGFR complexes unite to form a back-to-back
      dimer in which the ligands are on opposite sides of the aggregate. Following
      ligand binding, EGFR intracellular kinase domains form an asymmetric dimer. The
      carboxyterminal lobe of the activator kinase of the dimer interacts with the
      amino-terminal lobe of the receiver kinase thereby leading to its allosteric
      stimulation. Several malignancies are associated with the mutation or increased
      expression of members of the ErbB family including lung, breast, stomach,
      colorectal, head and neck, and pancreatic carcinomas. Gefitinib, erlotinib, and
      afatinib are orally effective protein-kinase targeted quinazoline derivatives
      that are used in the treatment of ERBB1-mutant lung cancer and lapatinib is an
      orally effective quinazoline derivative used in the treatment of ErbB2
      overexpressing breast cancer. Moreover, monoclonal antibodies that target the
      extracellular domain of ErbB2 are used for the treatment of ErbB2-positive breast
      cancer and monoclonal antibodies that target ErbB1 and are used for the treatment
      of colorectal cancer. Cancers treated with these targeted drugs eventually become
      resistant to them, and a current goal of research is to develop drugs that are
      effective against drug-resistant tumors. 

PMID- 24928737
TI  - Oxygen glucose deprivation-induced astrocyte dysfunction provokes neuronal death
      through oxidative stress.
AB  - Understanding the role of astrocytes in stroke is assuming increasing prominence,
      not only as an important component on its own within the neurovascular unit, but
      also because astrocytes can influence neuronal outcome. Ischemia may induce
      astrogliosis and other phenotypic changes, but these remain poorly understood, in
      part due to limitations in reproducing these changes in vitro. Dibutyryl cyclic
      AMP-differentiated cultured astrocytes are more representative of the in vivo
      astroglial cell phenotype, and were much more susceptible than undifferentiated
      astrocytes to an ischemic-like stress, oxygen-glucose deprivation (OGD). OGD
      altered the expression/distribution and activity of glial glutamate transporters,
      impaired cellular glutamate uptake and decreased intracellular levels of
      glutathione preferentially in differentiated astrocytes. Resistance to OGD was
      conferred by inhibiting caspase-3 with DEVD-CHO and oxidative stress by the
      antioxidant N-acetylcysteine (NAC). The resistance of undifferentiated astrocytes
      to OGD may result from a transient but selective morphological transformation
      into Alzheimer type II astrocytes, an intermediary stage prior to transforming
      into reactive astrocytes. Co-culture of neurons with OGD-exposed astrocytes
      resulted in neurotoxicity, but at surprisingly lower levels with dying
      differentiated astrocytes. The antioxidant NAC or the 5-LOX inhibitor AA861 added
      upon co-culture delayed (day 1) but did not prevent neurotoxicity (day 3).
      Astrocytes undergoing apoptosis as a result of ischemia may represent a transient
      neuroprotective mechanism via ischemia-induced release of glutathione, but
      oxidative stress was responsible for neuronal demise when ischemia compromised
      astrocyte supportive functions. 

PMID- 24928735
TI  - Maternal emotion regulation mediates the association between adult attention
      deficit/hyperactivity disorder symptoms and parenting.
AB  - Mothers with elevated Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms
      demonstrate parenting deficits, as well as difficulties in emotion regulation
      (ER), which may further impact their ability to effectively parent. However, no
      empirical research has examined potential mediators that explain the relations
      between maternal ADHD symptoms and parenting. This prospective longitudinal study
      examined difficulties with ER as a mediator of the relation between adult ADHD
      symptoms and parenting among 234 mothers of adolescents recruited from the
      community when they were between the ages of nine to twelve. Maternal ratings of
      adult ADHD symptoms, difficulties with ER, and parenting responses to their
      adolescents' expressions of negative emotions were collected over the course of
      three years. We found that maternal ADHD symptoms were negatively associated with
      positive parenting responses to adolescents' negative emotions, and positively
      associated with harsh parenting and maternal distress reactions. Moreover,
      maternal ER mediated the relation between adult ADHD symptoms and harsh parenting
      responses, while controlling for adolescent ADHD and disruptive behavior
      symptoms. However, maternal ER did not mediate the relation between ADHD symptoms
      and positive or distressed parental responses. Thus, it appears that ER is one
      mechanism by which maternal ADHD symptoms are associated with harsh responses to
      their adolescents' expressions of negative emotion. These findings may have
      downstream implications for adolescent adjustment.

PMID- 24928738
TI  - Robotic-assisted laparoscopy vs conventional laparoscopy for the treatment of
      advanced stage endometriosis.
AB  - STUDY OBJECTIVE: To compare robotic-assisted laparoscopy with conventional
      laparoscopy for treatment of advanced stage endometriosis insofar as operative
      time, estimated blood loss, complication rate, and length of hospital stay. STUDY
      DESIGN: Retrospective cohort study (Canadian Task Force classification II2). All
      procedures were performed by one surgeon between January 2004 and July 2012. Data
      was collected via chart review. SETTING: Tertiary referral center for treatment
      of endometriosis. PATIENTS: Four hundred twenty women with advanced
      endometriosis. INTERVENTIONS: Fertility-sparing surgery to treat advanced
      endometriosis, either via conventional or robotic-assisted laparoscopy.
      MEASUREMENTS AND MAIN RESULTS: Patient demographic data, operative time,
      estimated blood loss, complication rate, and length of hospital stay were
      compared between the 2 groups. Two hundred seventy-three patients underwent
      conventional laparoscopy and 147 patients underwent robotic-assisted laparoscopy
      for fertility-sparing treatment of advanced stage endometriosis. Patients in both
      groups had similar characteristics insofar as age, body mass index, and previous
      abdominal surgeries. There were no significant differences in blood loss or
      complication rate between the 2 groups. Mean operative time in the conventional
      laparoscopy group was 135 minutes (range, 115-156 minutes), and in the robotic
      assisted laparoscopy group was 196 minutes (range, 185-209 minutes), with a mean
      difference in operative time of 61 minutes (p < .001). Length of hospital stay
      was also significantly increased in the robotic-assisted laparoscopy group. Most
      patients who underwent conventional laparoscopy were discharged to home on the
      day of surgery. Of 273 patients in the conventional laparoscopy group, only 63
      remained in the hospital overnight, and all 147 patients in the robotic-assisted
      laparoscopy group were discharged on postoperative day 1. CONCLUSION:
      Conventional laparoscopy and robotic-assisted laparoscopy are excellent methods
      for treatment of advanced stages of endometriosis. However, use of the robotic
      platform may increase operative time and might also be associated with longer
      hospital stay.

PMID- 24928739
TI  - Single-port (OctoPort) assisted extracorporeal ovarian cystectomy for the
      treatment of large ovarian cysts: compare to conventional laparoscopy and
      laparotomy.
AB  - STUDY OBJECTIVE: To evaluate single-port assisted extracorporeal cystectomy for
      treatment of large ovarian cysts and to compare its surgical outcomes,
      complications, and cystic content spillage rates with those of conventional
      laparoscopy and laparotomy. DESIGN: Retrospective study (Canadian Task Force
      classification II-2). SETTING: University teaching hospital. PATIENTS: Twenty
      five patients who underwent single-port assisted extracorporeal cystectomy (group
      1), 33 patients who underwent conventional laparoscopy (group 2), and 25 patients
      who underwent laparotomy (group 3). INTERVENTIONS: Surgical outcomes,
      complications, and spillage rates in group 1 were compared with those in groups 2
      and 3. MEASUREMENTS AND MAIN RESULTS: Patients characteristics and tumor
      histologic findings were similar in the 3 groups. The mean (SD) largest diameter
      of ovarian cysts was 11.4 (4.2) cm in group 1, 9.7 (2.3) cm in group 2, and 12.0
      (3.4) cm in group 3. Operative time in groups 1 and 2 was similar at 69.3 (26.3)
      minutes vs 73.1 (36.3) minutes (p = .66); however, operative time in group 1 was
      shorter than in group 3, at 69.3 (26.3) minutes vs 87.5 (26.6) minutes (p =.02).
      Blood loss in group 1 was significantly lower than in groups 2 and 3, at 16.0
      (19.4) mL vs 36.1 (20.7) mL (p < .001) and 16.0 (19.4) mL vs 42.2 (39.7) mL (p =
      .005). The spillage rate in group 1 was profoundly lower than in group 2, at 8.0%
      vs 69.7% (p < .001). CONCLUSION: Single-port assisted extracorporeal cystectomy
      offers an alternative to conventional laparoscopy and laparotomy for management
      of large ovarian cysts, with comparable surgical outcomes. Furthermore, cyst
      content spillage rate in single-port assisted extracorporeal cystectomy was
      remarkably lower than that in conventional laparoscopy.

PMID- 24928740
TI  - Risk of leakage and tissue dissemination with various contained tissue extraction
      (CTE) techniques: an in vitro pilot study.
AB  - STUDY OBJECTIVE: To evaluate risk of leakage and tissue dissemination associated
      with various contained tissue extraction (CTE) techniques. DESIGN: In vitro study
      (Canadian Task Force classification: II-1). SETTING: Academic hospital simulation
      laboratory. INTERVENTION: Beef tongue specimens weighing 400 to 500 g were
      stained using 5 mL indigo carmine dye and morcellated under laparoscopic guidance
      within a plastic box trainer. CTE was performed via 3 different techniques: a
      stitch-sealed rip-stop nylon bag and multi-port approach; a one-piece clear
      plastic 50 * 50-cm isolation bag and multi-port approach; or a 1-piece clear
      plastic 50 * 50-cm isolation bag and single-site approach. Four trials of each
      CTE method were performed and compared with an open morcellation control. All
      bags were insufflated to within 10 to 25 mmHg pressure with a standard CO2
      insufflator. Visual evidence of spilled tissue or dye was recorded, and fluid
      washings of the box trainer were sent for cytologic analysis. MEASUREMENTS AND
      MAIN RESULTS: Blue dye spill was noted in only 1 of 12 CTE trials. Spillage was
      visualized from a seam in 1 of the 4 stitch-sealed rip-stop nylon bags before
      morcellation of the specimen. The only trial in which gross tissue chips were
      visualized in the box trainer after morcellation was the open morcellation
      control. However, cytologic examination revealed muscle cells in the open
      morcellation washings and in the washings from the trial with dye spill. Muscle
      cells were not observed at cytologly in any of the other samples. CONCLUSION: CTE
      did not result in any leakage or tissue dissemination with use of the single-site
      or multi-port approach when using a 1-piece clear plastic 50 * 50-cm isolation
      bag. Further studies are needed to corroborate these findings in an in vivo
      context and to evaluate use of alternate bag options for specimen containment.

PMID- 24928741
TI  - Deletion of potD, encoding a putative spermidine-binding protein, results in a
      complex phenotype in Legionella pneumophila.
AB  - L. pneumophila is an intracellular pathogen that replicates in a membrane-bound
      compartment known as the Legionella-containing vacuole (LCV). We previously
      observed that the polyamine spermidine, produced by host cells or added
      exogenously, enhances the intracellular growth of L. pneumophila. To study this
      enhancing effect and determine whether polyamines are used as nutrients, we
      deleted potD from L. pneumophila strain JR32. The gene potD encodes a spermidine
      binding protein that in other bacteria is essential for the function of the
      PotABCD polyamine transporter. Deletion of potD did not affect L. pneumophila
      growth in vitro in the presence or absence of spermidine and putrescine,
      suggesting that PotD plays a redundant or no role in polyamine uptake. However,
      deletion of potD resulted in a puzzlingly complex phenotype that included defects
      in L. pneumophila's ability to form filaments, tolerate Na(+), associate with
      macrophages and amoeba, recruit host vesicles to the LCV, and initiate
      intracellular growth. Moreover, the DeltapotD mutant was completely unable to
      grow in L929 cells treated with a pharmacological inhibitor of spermidine
      synthesis. These complex and disparate effects suggest that the L. pneumophila
      potD encodes either: (i) a multifunctional protein, (ii) a protein that interacts
      with, or regulates a, multifunctional protein, or (iii) a protein that
      contributes (directly or indirectly) to a regulatory network. Protein function
      studies with the L. pneumophila PotD protein are thus warranted. 

PMID- 24928742
TI  - Metabolite profiling analysis of FR429, an ellagitannin purified from Polygonum
      capitatum, in rat and human liver microsomes, cytosol and rat primary hepatocytes
      in vitro.
AB  - FR429, an ellagitannin (a type of polyphenol), is isolated and purified from
      Polygonum capitatum Buch.-Ham.ex D. Don which is the original herbal medicine of
      the "Re-Lin-Qing" formula used clinically to treat urinary tract infection in
      China. FR429 has been investigated for its antitumor potential in tumor-bearing
      nude mice in vivo, but its in vitro anti-tumor effect in hepatoma cell lines was
      low. Thus, it was of our interest to investigate its metabolism pathways for
      supporting its in vivo antitumor potential. The metabolic profiles of FR429 were
      studied in vitro by liquid chromatography coupled to ion trap time-of-flight mass
      spectrometry. Total eight metabolites were identified in rat and human liver
      microsomes, cytosol, and rat primary hepatocytes in vitro. Ellagic acid, a
      reported anti-angiogenic agent, was one of the main metabolites in these
      biological matrices. Methylated metabolites catalyzed by catechol-O-methyl
      transferase (COMT) were observed mainly in the in vitro incubation with rat liver
      cytosol, which was verified by using a COMT specific inhibitor entacapone and
      supported by molecular docking analysis. Methylated and sulfated metabolites were
      also found in rat primary hepatocytes in a time-dependent manner. In conclusion,
      the in vitro metabolism pathways of FR429 were hydrolysis, methylation and
      sulfation. The anti-tumor effects of its major metabolites should be further
      studied. 

PMID- 24928744
TI  - [Not Available].

PMID- 24928743
TI  - Nanodiamond-mediated impairment of nucleolar activity is accompanied by oxidative
      stress and DNMT2 upregulation in human cervical carcinoma cells.
AB  - Because applications of nanomaterials in nanomedicine and nanotechnology are
      rapidly increasing, nanodiamond (ND) health risk assessment is urgently needed.
      In the present study, we used HeLa cell model to evaluate nanodiamond
      biocompatibility. We found ND-mediated cytotoxicity, proliferation inhibition and
      oxidative stress. Conversely, ND-associated genotoxicity was limited to higher
      concentrations used. Nanodiamond was also recognized as a hypermethylating agent.
      ND-associated redox imbalance contributed to nucleolar stress: size and number of
      nucleoli were affected, and release of nucleolar protein RRN3 occurred.
      Surprisingly, we did not observe stress-induced RNA depletion. In contrast, RNA
      was stabilized: total RNA level and integrity (28S/18S rRNA ratio) were
      unaffected. After nanodiamond treatment, upregulation of DNA methyltransferase 2
      (DNMT2) was shown. Perhaps, DNMT2, as a part of the regulatory loop of metabolic
      pathways through RNA methylation, may contribute to RNA stabilization and confer
      stress resistance after nanodiamond treatment. In conclusion, using HeLa cell
      model, we showed that ND biocompatibility is limited and special care should be
      taken when introducing ND-based biomaterials to biological systems. 

PMID- 24928745
TI  - [Not Available].

PMID- 24928746
TI  - [Not Available].

PMID- 24928747
TI  - [Not Available].

PMID- 24928748
TI  - [Not Available].

PMID- 24928749
TI  - [Not Available].

PMID- 24928750
TI  - [Comment to article "Difficult intubation with Airtraq(r) and fibreoptic
      bronchoscope in an awake patient with parapharyngeal abscess"].

PMID- 24928751
TI  - Embarked electrical network robust control based on singular perturbation model.
AB  - This paper deals with an approach of modelling in view of control for embarked
      networks which can be described as strongly coupled multi-sources, multi-loads
      systems with nonlinear and badly known characteristics. This model has to be
      representative of the system behaviour and easy to handle for easy regulators
      synthesis. As a first step, each alternator is modelled and linearized around an
      operating point and then it is subdivided into two lower order systems according
      to the singular perturbation theory. RST regulators are designed for each
      subsystem and tested by means of a software test-bench which allows predicting
      network behaviour in both steady and transient states. Finally, the designed
      controllers are implanted on an experimental benchmark constituted by two
      alternators supplying loads in order to test the dynamic performances in
      realistic conditions. 

PMID- 24928754
TI  - Odorant binding characteristics of three recombinant odorant binding proteins in
      Microplitis mediator (Hymenoptera: Braconidae).
AB  - Odorant binding proteins (OBPs) are believed to be important for transporting
      semiochemicals through the aqueous sensillar lymph to the olfactory receptor
      cells within the insect antennal sensilla. In this study, three new putative OBP
      genes, MmedOBP8-10, were identified from a Microplitis mediator (Hymenoptera:
      Braconidae) antennal cDNA library. Quantitative real-time PCR (qRT-PCR) analysis
      revealed that all three of the OBP genes were expressed mainly in the antennae of
      adult wasps. The three OBPs were recombinantly expressed in Escherichia coli and
      purified by Ni ion affinity chromatography. Fluorescence competitive binding
      assays were performed using N-phenyl-naphthylamine as a fluorescent probe and 45
      small organic compounds as competitors. These assays demonstrated that the three
      M. mediator OBPs can bind a broad range of odorant molecules with different
      binding affinities. They can bind the following ligands: nonane, farnesol,
      nerolidol, nonanal, beta-ionone, acetic ether, and farnesene. In a Y-tube assay
      with these ligands as odor stimuli and paraffin oil as a control, all ligands,
      except nerolidol and acetic ether, were able to elicit behavioral responses in
      adult M. mediator. The wasps were significantly attracted to beta-ionone,
      nonanal, and farnesene and repelled by nonane and farnesol. The results of this
      work provide insight into the chemosensory functions of the OBPs in M. mediator. 

PMID- 24928755
TI  - Evidence-Based Practice Projects in Pediatric Oncology Nursing.
AB  - This introduction article discusses the history and importance of evidence-based
      practice, along with describing the process that 6 nurse-led teams completed for
      the systematic reviews listed in this journal issue.

PMID- 24928756
TI  - Neutropenia Precautions for Children Receiving Chemotherapy or Stem Cell
      Transplantation for Cancer.
AB  - Infections in children and adolescents with cancer are a significant cause of
      morbidity and mortality, especially in those receiving chemotherapy who are
      neutropenic and/or immunocompromised. The aim of this article is to review
      existing evidence in order to provide a practice recommendation to prevent or
      minimize infections in neutropenic and/or immunocompromised patients receiving
      chemotherapy and/or stem cell transplant. Systematic reviews were undertaken and
      research was graded according to the Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE) criteria. A variety of interventions are
      implemented to reduce infections in the neutropenic and/or immunocompromised
      population; however, few are supported by research evidence. Existing literature
      should continue to be reviewed to further identify interventions that can
      influence positive patient outcomes and provide opportunities for individuals in
      the medical field to work together to improve clinical care.

PMID- 24928757
TI  - Evidence-Based Practice Recommendations to Prevent/Manage Post-Lumbar Puncture
      Headaches in Pediatric Patients Receiving Intrathecal Chemotherapy.
AB  - Post-lumbar puncture headaches (PLPHs) are a known complication of lumbar
      puncture procedures. Children undergoing treatment for cancer often undergo
      multiple lumbar punctures, placing them at increased risk for PLPHs. There are
      currently no guidelines for the prevention or management of PLPHs in children. A
      team was therefore assembled to conduct a systematic review of the evidence in
      relationship to PLPHs in the pediatric population. Clinical questions were
      developed and used to guide the literature review. Twenty-four articles were
      deemed appropriate for use and were evaluated using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) criteria. Based on
      the review of evidence, strong recommendations are made for the use of smaller
      needle sizes and for the use of pencil point needles during lumbar puncture
      procedures. Weak recommendations are made for needle orientation and positioning
      following the procedure as well as for interventions used to treat PLPHs once
      they occur. There is a need for additional, pediatric-specific studies to further
      examine the issue of PLPH prevention and treatment.

PMID- 24928758
TI  - Psychological distress in an earthquake-devastated area with pre-existing high
      rate of suicide.
AB  - On 12 March 2011 an earthquake devastated the Matsunoyama and Matsudai districts
      of Tokamachi City, Niigata, Japan. These areas had high pre-existing suicide
      rates, especially among the elderly. We investigated whether mental health status
      became worse among the sufferers 5 months after the earthquake, and what kind of
      factors were implicated in any changes. A 15-item questionnaire that tapped
      earthquake-related variables and the Kessler 10 Psychological Distress Scale to
      measure psychological distress were distributed to 1923 residents aged over 40
      years. The mean age (S.D.) of the total 1731 respondents (male, 805; female, 926)
      was 68.2 (13.1) years. Of these, we assessed K10 scores from 1346 respondents.
      The mean scores (S.D.) for K10 and K6 (six selected items from the K10) were 5.8
      (6.3) and 3.4 (3.9), respectively. Among the respondents, 9.1% and 3.2% obtained
      a score of K10 >=15 and K6 >=13, respectively. These scores showed slightly
      higher psychological distress, especially among the elderly, in comparison with
      existing community-based data. Categorical regression analysis revealed
      significant and relatively strong effects of initial psychological impact,
      decrease in sleep hours, advanced age, and decrease in interpersonal
      relationships within the community on the K10 score. The last item suggests the
      importance of socio-environmental factors in post-disaster mental health. 

PMID- 24928759
TI  - Associations between obsessive-compulsive symptoms, revenge, and the perception
      of interpersonal transgressions.
AB  - Anger and aggression have only recently gained center stage in research on
      obsessive-compulsive disorder (OCD). An investigation of obsessive-compulsive
      (OC) symptoms focusing on the outcome of unresolved anger (i.e., revenge),
      however, is absent from the literature. The objective of the present research was
      therefore to provide a first step towards filling this gap and, hence, to
      systematically examine the associations between OC symptoms and different aspects
      of revenge (i.e., attitudes, dispositions, motivations). In three independent
      studies with nonclinical participants (N=504), we tested the hypothesis that OC
      symptoms relate to greater revenge. Individuals high in OC symptoms reported more
      positive attitudes toward revenge (Study 1), scored higher on a measure of trait
      revenge (Study 2), and reported increased revenge motivation regarding a real
      life transgressor (Study 3). Furthermore, Study 4 (N=175) demonstrated that
      individuals high in OC symptoms perceived interpersonal transgressions more
      frequently in their daily lives. OC symptoms were positively related to the
      number of transgressions that respondents disclosed. Our results suggest that
      revenge and interpersonal hurt play a significant role in OCD. 

PMID- 24928760
TI  - Meniscal allograft transplantation: a systematic review.
AB  - BACKGROUND: Meniscal allograft transplantation (MAT) was developed as a means of
      treating the symptoms of compartmental overload after meniscectomy. Despite more
      than 20 years of research in this field, many controversies still exist regarding
      meniscal transplantation. PURPOSE: The aims of this study were to assess (1) the
      quality of the published studies on MAT; (2) the indications for this type of
      surgery; (3) the methods used for preservation, sizing, and fixation of the
      allograft; and (4) the clinical and radiographic outcomes of this procedure and
      its role in preventing osteoarthritis. STUDY DESIGN: Systematic review. METHODS:
      Inclusion criteria for the articles were (1) English language, (2) peer-reviewed
      clinical studies with evidence levels 1 to 4, (3) reported clinical and/or
      radiological outcomes of MAT isolated or combined with other procedures, (4)
      minimum 12-month follow-up, (5) case series of at least 10 patients, and (6) a
      follow-up rate of at least 80% (no more than 20% of patients lost to follow-up).
      RESULTS: A total of 55 studies matched the inclusion criteria (2 level 2, 7 level
      3, and 46 level 4). The average Coleman methodology score was 49.73 +/- 12.41
      (range, 24-81). There was agreement in the literature regarding the indications
      for MAT: joint line pain and tenderness correlated with previous meniscectomy,
      young patients, without diffuse Outerbridge grade III and no grade IV cartilage
      damage, and a stable and well-aligned knee. Different graft types have been used:
      viable, fresh frozen, cryopreserved, and lyophilized. The most common method for
      graft sizing was plain radiography. Different fixation techniques have been
      described, with only a few studies comparing the clinical results of the
      different techniques and with no proven superiority of one method over the other.
      All the studies showed clinical improvement at last follow-up visit compared with
      preoperatively. The chondroprotective effect of MAT is still unclear. CONCLUSION:
      Meniscal allograft transplantation seems to provide good clinical results at
      short-term and midterm follow-up, with improvement in knee function as well as
      acceptable complication and failure rates. Higher quality studies are necessary
      to better assess the potential chondroprotective effect of MAT and to identify
      differences in terms of outcomes between different surgical techniques.

PMID- 24928761
TI  - The influence of cervical muscle characteristics on head impact biomechanics in
      football.
AB  - BACKGROUND: An athlete is thought to reduce head acceleration after impact by
      contracting the cervical musculature, which increases the effective mass of the
      head. PURPOSE: To compare the odds of sustaining higher magnitude in-season head
      impacts between athletes with higher and lower preseason performance on cervical
      muscle characteristics. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: Forty-nine high school and collegiate American football players
      completed a preseason cervical testing protocol that included measures of
      cervical isometric strength, muscle size, and response to cervical perturbation.
      Head impact biomechanics were captured for each player using the Head Impact
      Telemetry System. A median split was used to categorize players as either high or
      low performers for each of the following outcome measures: isometric strength
      (peak torque, rate of torque development), muscle size (cross-sectional area),
      and response to cervical perturbation (stiffness, angular displacement, muscle
      onset latency). The odds of sustaining moderate and severe head impacts were
      computed against the reference odds of sustaining mild head impacts across
      cervical characteristic categorizations. RESULTS: Linemen with stronger lateral
      flexors and composite cervical strength had about 1.75 times' increased odds of
      sustaining moderate linear head impacts rather than mild impacts compared with
      weaker linemen. Players who developed extensor torque more quickly had 2 times
      the increased odds of sustaining severe linear head impacts (odds ratio [OR],
      2.10; 95% CI, 1.08-4.05) rather than mild head impacts. However, players with
      greater cervical stiffness had reduced odds of sustaining both moderate (OR,
      0.77; 95% CI, 0.61-0.96) and severe (OR, 0.64; 95% CI, 0.46-0.89) head impacts
      compared with players with less cervical stiffness. CONCLUSION: The study
      findings showed that greater cervical stiffness and less angular displacement
      after perturbation reduced the odds of sustaining higher magnitude head impacts;
      however, the findings did not show that players with stronger and larger neck
      muscles mitigate head impact severity.

PMID- 24928763
TI  - Reproducibility of the Carpet View system: a novel technical solution for display
      and off line analysis of OCT images.
AB  - The optical coherence tomography (OCT) evaluation of the stent anatomy requires
      the inspection of sequential cross section (CS). However stent coils cannot be
      appreciated in the conventional format as the OCT CS simply display stent struts,
      that are poorly representative of the stent architecture. The aim of the present
      study was to validate a new software (Carpet View), which unfolds the stented
      segment, reconstructing it as an open structure and displaying the stent
      meshwork. 21 patients were studied with frequency domain OCT after the deployment
      of different stents: seven bio-absorbable scaffolds (Dream), seven bare metal
      stent (Vision/Multilink8), seven drug eluting stent (Cre8). Conventional CS
      reconstructions were post-processed with the Carpet View software and analyzed by
      the same reader twice (intra-observer variability) and by two different readers
      (inter-observer variability). A small average difference in the number of all
      struts was obtained with the two methods (conventional vs carpet view
      reconstruction). Using the carpet view, high intra-observer and inter-observer
      correlations were found for the number of struts obtained in each coil. The
      Pearson correlation values were 0.98 (p = 0.0001) and 0.96 (p = 0.0001)
      respectively. The same number of coils was found when analyses were repeated by
      the same reader or by a different reader whilst mild differences in the count of
      stent junctions were reported. The Carpet View can be used to address the stent
      geometry with high reproducibility. This approach enables the matching of the
      same stent portion during serial time points and promises to improve the stent
      assessment.

PMID- 24928762
TI  - Terminate and make a loop: regulation of transcriptional directionality.
AB  - Bidirectional promoters are a common feature of many eukaryotic organisms from
      yeast to humans. RNA Polymerase II that is recruited to this type of promoter can
      start transcribing in either direction using alternative DNA strands as the
      template. Such promiscuous transcription can lead to the synthesis of unwanted
      transcripts that may have negative effects on gene expression. Recent studies
      have identified transcription termination and gene looping as critical players in
      the enforcement of promoter directionality. Interestingly, both mechanisms share
      key components. Here, we focus on recent findings relating to the transcriptional
      output of bidirectional promoters. 

PMID- 24928764
TI  - Automated assessment and 3-dimensional visualization of the pattern of neointimal
      tissue maturity in vivo following drug-eluting stent implantation.

PMID- 24928765
TI  - Influence of the cardiac cycle on time-intensity curves using multislice dynamic
      magnetic resonance perfusion.
AB  - Flow and pressure variations cause potential changes in magnetic resonance
      imaging (MRI) signal intensity across the cardiac cycle. Nevertheless, cardiac
      dynamic contrast-enhanced (perfusion) MRI is performed and analyzed regardless of
      the cardiac phase. We investigate whether the cardiac phase impacts myocardial
      and left ventricle (LV) cavity time intensity curves (TICs) at rest and during
      vasodilatation. Fifteen healthy volunteers (seven females, eight males; mean age:
      32.5 +/- 9.3 years; age range: 19-49 years) were included in this prospective
      study. They underwent four separate short-axis multislice (apical, mid and basal)
      LV perfusion MRI, with different electrocardiogram-triggering during normal
      vasotone and adenosine-stress. TIC parameters were extracted from the myocardium
      and the LV cavity. General linear mixed model analyses were used to evaluate
      their variability according to vasotone, cardiac phase and slice-position.
      Maximal enhancement and normalized Steepest slopes were higher at stress than at
      rest (p values <0.001). A similar trend towards higher inflow was shown on
      systole versus diastole in the LV cavity and diastole versus systole in the
      myocardium (p < 0.05).These TIC parameters were slice-position dependent, as the
      inflow decreased from the base to the apex in the LV, and peaked on the mid-slice
      for the myocardium. There are significant variability of both the LV and the
      myocardial TICs, with respect to the cardiac cycle phase and the slice position
      where imaging actually takes place. These appeal to measurement standardization
      for a better intra- and inter-study reproducibility.

PMID- 24928766
TI  - Dietary levels of acrylamide affect rat cardiomyocyte properties.
AB  - The toxic effects of acrylamide on cytoskeletal integrity and ion channel balance
      is well-established in many cell types, but there has been little examination
      regarding the effects of acrylamide on primary cardiomyocytes, despite the
      importance of such components in their function. Furthermore, acrylamide toxicity
      is generally examined using concentrations higher than those found in vivo under
      starch-rich diets. Accordingly, we sought to characterize the dose-dependent
      effects of acrylamide on various properties, including cell morphology,
      contraction patterns, and junctional connexin 43 staining, in primary
      cardiomyocytes. We show that several days exposure to 1-100 MUM acrylamide
      resulted in altered morphology, irregular contraction patterns, and an increase
      in the amount of immunoreactive signal for connexin 43 at cell junctions. We
      conclude that dietary levels of acrylamide may alter cellular function with
      prolonged exposure, in primary cardiomyocytes.

PMID- 24928767
TI  - An investigation of facial emotion recognition impairments in alexithymia and its
      neural correlates.
AB  - Alexithymia is a personality trait that involves difficulties identifying
      emotions and describing feelings. It is hypothesized that this includes facial
      emotion recognition but limited knowledge exists about possible neural correlates
      of this assumed deficit. We hence tested thirty-seven healthy subjects with
      either a relatively high or low degree of alexithymia (HDA versus LDA), who
      performed in a reliable and standardized test of facial emotion recognition
      (FEEL, Facially Expressed Emotion Labeling) in the functional MRI. LDA subjects
      had significantly better emotion recognition scores and showed relatively more
      activity in several brain areas associated with alexithymia and emotional
      awareness (anterior cingulate cortex), and the extended system of facial
      perception concerned with aspects of social communication and emotion (amygdala,
      insula, striatum). Additionally, LDA subjects had more activity in the visual
      area of social perception (posterior part of the superior temporal sulcus) and
      the inferior frontal cortex. HDA subjects, on the other hand, exhibited greater
      activity in the superior parietal lobule. With differences in behaviour and brain
      responses between two groups of otherwise healthy subjects, our results
      indirectly support recent conceptualizations and epidemiological data, that
      alexithymia is a dimensional personality trait apparent in clinically healthy
      subjects rather than a categorical diagnosis only applicable to clinical
      populations. 

PMID- 24928768
TI  - Involvement of the serotonergic system in the anxiolytic-like effect of 2
      phenylethynyl butyltellurium in mice.
AB  - Anxiety is a serious disorder with symptoms manifested at the psychological,
      behavioral, and physiological levels, accompanied by alterations in the
      serotonergic system and monoaminergic signaling. In this study, the anxiolytic
      like effect of 2-phenylethynyl butyltellurium (PEBT), in three well-consolidated
      anxiety mouse models (light-dark test, novelty suppressed-feeding, elevated plus
      maze), was investigated. The involvement of the serotonergic system, synaptosomal
      [(3)H] serotonin (5-HT) uptake and monoamine oxidase (MAO A and B) activities on
      cerebral cortices of mice, was examined. Mice received PEBT (1mg/kg, by
      intragastric route, i.g.) or canola oil (10 ml/kg, i.g.) 30 min before behavioral
      tests. The results showed that PEBT was effective in increasing the time spent by
      mice in the illuminated side on the light-dark box and in the open arms on the
      elevated plus-maze. PEBT decreased the latency to begin eating on the novelty
      suppressed-feeding test, indicating an anxiolytic-like effect of PEBT.
      Furthermore, PEBT reduced [(3)H] 5-HT uptake and selectively inhibited MAO-A
      activity in cerebral cortex, suggesting the involvement of the serotonergic
      system in the mechanism of action of this tellurium compound.

PMID- 24928769
TI  - Life without brain serotonin: reevaluation of serotonin function with mice
      deficient in brain serotonin synthesis.
AB  - Tryptophan hydroxylase (TPH) is a rate limiting enzyme in the synthesis of
      serotonin (5-HT), a monoamine which works as an autacoid in the periphery and as
      a neurotransmitter in the central nervous system. In 2003 we have discovered the
      existence of a second Tph gene, which is expressed exclusively in the brain, and,
      therefore, is responsible for the 5-HT synthesis in the central nervous system.
      In the following years several research groups have independently generated Tph2
      deficient mice. In this review we will summarize the data gained from the
      existing mouse models with constitutive or conditional deletion of the Tph2 gene,
      focusing on biochemical, developmental, and behavioral consequences of Tph2
      deficiency. 

PMID- 24928770
TI  - NK3 receptor agonism reinstates temporal order memory in the hemiparkinsonian
      rat.
AB  - Animals treated with unilateral 6-hydroxydopamine (6-ODHA) injections, an animal
      model of Parkinson's disease, exhibit deficits in memory for temporal order, but
      show intact novel object recognition. Since senktide, a potent neurokinin-3
      receptor (NK3-R) agonist, has been shown to have promnestic effects in the aged
      rat and to alleviate scopolamine-induced impairment, the present study aimed to
      assess possible promnestic effects of senktide in the hemiparkinsonian rat model.
      Animals received unilateral 6-ODHA microinjections into the medial forebrain
      bundle. Two weeks later, they were randomly assigned to treatment with vehicle,
      0.2, or 0.4 mg/kg senktide. Temporal order memory and place recognition tests
      were conducted, locomotor activity and turning behavior were assessed in the open
      field and anxiety-related behavior was measured in the light-dark box. Treatments
      were administered 30 min prior to behavioral testing with an interval of seven
      days between tests. The animals treated with 0.2 mg/kg senktide exhibited
      temporal order memory, unlike the vehicle-treated group. No significant treatment
      effects were found in the open field and light-dark box. Administration of 0.2
      mg/kg senktide may influence the prefrontal cortex and hippocampus, leading to
      compensations for deficits in memory for temporal order.

PMID- 24928771
TI  - Roles of genomic island 3 (GI-3) BAB1_0267 and BAB1_0270 open reading frames
      (ORFs) in the virulence of Brucella abortus 2308.
AB  - One of the properties of bacteria is their capacity to acquire large fragments of
      genomic DNA from other bacteria or to loose important parts of their own genome.
      Such fragments include genomic islands (GIs); nine GIs are present in Brucella,
      including genomic island 3 (GI-3), present in B. abortus, B. melitensis and B.
      ovis. The GI-3 have 29 open reading frames (ORFs) most of them with unknown
      function. Within the GI-3, the ORFs BAB1_0267 encodes a hypothetical protein
      sharing a SH3 domain and BAB1_270 a zinc-dependent metallopeptidase. We have
      obtained deletion mutants for BAB1_0267 and BAB1_0270 ORFs present within GI-3,
      which have been named the Delta0267 and Delta0270, respectively; in both cases
      the mutation did not affect the growth of bacteria. Both mutants were evaluated
      with respect to their growth rates, their ability to invade and replicate in the
      non-professional and professional phagocytes, HeLa and J774.A1 cells,
      respectively. Their persistence in the spleens of mice was also evaluated. The
      mutants efficiently invaded HeLa and J774.A1 cells but both mutants showed a
      decreased intracellular survival in macrophages and HeLa cells 72 and 96 h post
      infection, respectively, and were non-detected in J774.A1 cells 120 h post
      infection. With respect to in vivo persistence Delta0267 was detected through the
      fourth week while Delta0270 decreased at 7 days disappearing the second week. Our
      results indicated that deletion of BAB1_0267 and BAB1_270 are necessary to
      establish an optimal infectious process in B. abortus 2308, having more effect
      the deletion of ORF BAB1_0270. Therefore these ORFs, principally BAB1_0270 are
      important virulent of B. abortus.

PMID- 24928773
TI  - Surface characterization of lithium disilicate ceramic after nonthermal plasma
      treatment.
AB  - STATEMENT OF PROBLEM: Surface transformation with nonthermal plasma may be a
      suitable treatment for dental ceramics, because it does not affect the physical
      properties of the ceramic material. PURPOSE: The purpose of this study was to
      characterize the chemical composition of lithium disilicate ceramic and evaluate
      the surface of this material after nonthermal plasma treatment. MATERIAL AND
      METHODS: A total of 21 specimens of lithium disilicate (10 mm in diameter and 3
      mm thick) were fabricated and randomly divided into 3 groups (n=7) according to
      surface treatment. The control group was not subjected to any treatment except
      surface polishing with abrasive paper. In the hydrofluoric acid group, the
      specimens were subjected to hydrofluoric acid gel before silane application.
      Specimens in the nonthermal plasma group were subjected to the nonthermal plasma
      treatment. The contact angle was measured to calculate surface energy. In
      addition, superficial roughness was measured and was examined with scanning
      electron microscopy, and the chemical composition was characterized with energy
      dispersive spectroscopy analysis. The results were analyzed with ANOVA and the
      Tukey honestly significant difference test (alpha=.05). RESULTS: The water
      contact angle was decreased to 0 degrees after nonthermal plasma treatment. No
      significant difference in surface roughness was observed between the control and
      nonthermal plasma groups. Scanning electron microscopy and energy-dispersive
      spectroscopy images indicated higher amounts of oxygen (O) and silicon (Si) and a
      considerable reduction in carbon (C) in the specimens after nonthermal plasma
      treatment. CONCLUSIONS: Nonthermal plasma treatment can transform the
      characteristics of a ceramic surface without affecting its surface roughness. A
      reduction in C levels and an increase in O and Si levels were observed with the
      energy-dispersive spectroscopy analysis, indicating that the deposition of the
      thin silica film was efficient.

PMID- 24928772
TI  - Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with
      four chemotherapy regimens for the treatment of patients with solid tumors: an
      open-label, multicenter phase 1b study.
AB  - C-C chemokine ligand 2 (CCL2) stimulates tumor growth, metastasis, and
      angiogenesis. Carlumab, a human IgG1kappa anti-CCL2 mAb, has shown antitumor
      activity in preclinical and clinical trials. We conducted a first-in-human phase
      1b study of carlumab with one of four chemotherapy regimens (docetaxel,
      gemcitabine, paclitaxel + carboplatin, and pegylated liposomal doxorubicin HCl
      [PLD]). Patients had advanced solid tumors for which >=1 of these regimens was
      considered standard of care or for whom no other treatment options existed. Dose
      limiting toxicities included one grade 4 febrile neutropenia (docetaxel arm) and
      one grade 3 neutropenia (gemcitabine arm). Combination treatment with carlumab
      had no clinically relevant pharmacokinetic effect on docetaxel (n = 15),
      gemcitabine (n = 12), paclitaxel or carboplatin (n = 12), or PLD (n = 14). Total
      serum CCL2 concentrations increased post-treatment with carlumab alone,
      consistent with carlumab-CCL2 binding, and continued increase in the presence of
      all chemotherapy regimens. Free CCL2 declined immediately post-treatment with
      carlumab but increased with further chemotherapy administrations in all arms,
      suggesting that carlumab could sequester CCL2 for only a short time. Neither
      antibodies against carlumab nor consistent changes in circulating tumor cells
      (CTCs) or circulating endothelial cells (CECs) enumeration were observed. Three
      of 19 evaluable patients showed a 30 % decrease from baseline urinary cross
      linked N-telopeptide of type I collagen (uNTx). One partial response and 18 (38
      %) stable disease responses were observed. The most common drug-related grade >=3
      adverse events were docetaxel arm-neutropenia (6/15) and febrile neutropenia
      (4/15); gemcitabine arm-neutropenia (2/12); paclitaxel + carboplatin arm
      neutropenia, thrombocytopenia (4/12 each), and anemia (2/12); and PLD arm-anemia
      (3/14) and stomatitis (2/14). Carlumab could be safely administered at 10 or 15
      mg/kg in combination with standard-of-care chemotherapy and was well-tolerated,
      although no long-term suppression of serum CCL2 or significant tumor responses
      were observed. 

PMID- 24928774
TI  - A kinetic model of Escherichia coli core metabolism satisfying multiple sets of
      mutant flux data.
AB  - In contrast to stoichiometric-based models, the development of large-scale
      kinetic models of metabolism has been hindered by the challenge of identifying
      kinetic parameter values and kinetic rate laws applicable to a wide range of
      environmental and/or genetic perturbations. The recently introduced ensemble
      modeling (EM) procedure provides a promising remedy to address these challenges
      by decomposing metabolic reactions into elementary reaction steps and
      incorporating all phenotypic observations, upon perturbation, in its model
      parameterization scheme. Here, we present a kinetic model of Escherichia coli
      core metabolism that satisfies the fluxomic data for wild-type and seven mutant
      strains by making use of the EM concepts. This model encompasses 138 reactions,
      93 metabolites and 60 substrate-level regulatory interactions accounting for
      glycolysis/gluconeogenesis, pentose phosphate pathway, TCA cycle, major pyruvate
      metabolism, anaplerotic reactions and a number of reactions in other parts of the
      metabolism. Parameterization is performed using a formal optimization approach
      that minimizes the discrepancies between model predictions and flux measurements.
      The predicted fluxes by the model are within the uncertainty range of
      experimental flux data for 78% of the reactions (with measured fluxes) for both
      the wild-type and seven mutant strains. The remaining flux predictions are mostly
      within three standard deviations of reported ranges. Converting the EM-based
      parameters into a Michaelis-Menten equivalent formalism revealed that 35% of Km
      and 77% of kcat parameters are within uncertainty range of the literature
      reported values. The predicted metabolite concentrations by the model are also
      within uncertainty ranges of metabolomic data for 68% of the metabolites. A leave
      one-out cross-validation test to evaluate the flux prediction performance of the
      model showed that metabolic fluxes for the mutants located in the proximity of
      mutations used for training the model can be predicted more accurately. The
      constructed model and the parameterization procedure presented in this study pave
      the way for the construction of larger-scale kinetic models with more narrowly
      distributed parameter values as new metabolomic/fluxomic data sets are becoming
      available for E. coli and other organisms. 

PMID- 24928776
TI  - Editorial comment.

PMID- 24928775
TI  - Social disadvantage and asthma control in children.
AB  - This review discusses various aspects of social disadvantage and their
      association with poor asthma control, including socioeconomic status, exposure to
      psychosocial stress and violence, minority affiliation, environmental concerns
      such as allergens and pollution, and poverty in rural settings. Each of these
      elements has been linked with worsened asthma outcomes in children. Known and
      hypothesized mechanisms behind these associations are described in an effort to
      further understand the complex entity of poorly controlled asthma among socially
      deprived children. Intervention studies to improve asthma outcomes in these
      vulnerable populations are also described. 

PMID- 24928777
TI  - Editorial comment.

PMID- 24928778
TI  - The use of repeated exposure and associative conditioning to increase vegetable
      acceptance in children: explaining the variability across studies.

PMID- 24928779
TI  - A comparison of food refusal related to characteristics of food in children with
      autism spectrum disorder and typically developing children.
AB  - Parents of children with autism spectrum disorder (ASD) frequently report child
      food refusal based on characteristics of food. Our study sought to determine
      whether parent report of food refusal based on the characteristics of food was
      greater in children with ASD than in typically developing children, associated
      with a greater percentage of foods refused of those offered, and associated with
      fruit and vegetable intake. A modified food frequency questionnaire was used to
      determine overall food refusal as well as fruit and vegetable intake. Parent
      reported food refusal related to characteristics of food (eg,
      texture/consistency, temperature, brand, color, shape, taste/smell, foods mixed
      together, or foods touching other foods) was compared between 53 children with
      ASD and 58 typically developing children aged 3 to 11 years in the Children's
      Activity and Meal Patterns Study (2007-2008). Children with ASD were
      significantly more likely to refuse foods based on texture/consistency (77.4% vs
      36.2%), taste/smell (49.1% vs 5.2%), mixtures (45.3% vs 25.9%), brand (15.1% vs
      1.7%), and shape (11.3% vs 1.7%). No differences between groups were found for
      food refusal based on temperature, foods touching other foods, or color.
      Irrespective of ASD status, the percentage of foods refused of those offered was
      associated with parent reports of food refusal based on all characteristics
      examined, except temperature. Food refusal based on color was inversely
      associated with vegetable consumption in both groups. Routine screening for food
      refusal among children with ASD is warranted to prevent dietary inadequacies that
      may be associated with selective eating habits. Future research is needed to
      develop effective and practical feeding approaches for children with ASD. 

PMID- 24928780
TI  - A free new dietary supplement label database for registered dietitian
      nutritionists.

PMID- 24928781
TI  - Cell surface lactate receptor GPR81 is crucial for cancer cell survival.
AB  - The mechanisms that allow cancer cells to adapt to the typical tumor
      microenvironment of low oxygen and glucose and high lactate are not well
      understood. GPR81 is a lactate receptor recently identified in adipose and muscle
      cells that has not been investigated in cancer. In the current study, we examined
      GPR81 expression and function in cancer cells. We found that GPR81 was present in
      colon, breast, lung, hepatocellular, salivary gland, cervical, and pancreatic
      carcinoma cell lines. Examination of tumors resected from patients with
      pancreatic cancer indicated that 94% (148 of 158) expressed high levels of GPR81.
      Functionally, we observed that the reduction of GPR81 levels using shRNA-mediated
      silencing had little effect on pancreatic cancer cells cultured in high glucose,
      but led to the rapid death of cancer cells cultured in conditions of low glucose
      supplemented with lactate. We also observed that lactate addition to culture
      media induced the expression of genes involved in lactate metabolism, including
      monocarboxylase transporters in control, but not in GPR81-silenced cells. In
      vivo, GPR81 expression levels correlated with the rate of pancreatic cancer tumor
      growth and metastasis. Cells in which GPR81 was silenced showed a dramatic
      decrease in growth and metastasis. Implantation of cancer cells in vivo was also
      observed to lead to greatly elevated levels of GPR81. These data support that
      GPR81 is important for cancer cell regulation of lactate transport mechanisms.
      Furthermore, lactate transport is important for the survival of cancer cells in
      the tumor microenvironment. Cancer Res; 74(18); 5301-10. (c)2014 AACR. 

PMID- 24928782
TI  - PME-1 modulates protein phosphatase 2A activity to promote the malignant
      phenotype of endometrial cancer cells.
AB  - Protein phosphatase 2A (PP2A) negatively regulates tumorigenic signaling
      pathways, in part, by supporting the function of tumor suppressors like p53. The
      PP2A methylesterase PME-1 limits the activity of PP2A by demethylating its
      catalytic subunit. Here, we report the finding that PME-1 overexpression
      correlates with increased cell proliferation and invasive phenotypes in
      endometrial adenocarcinoma cells, where it helps maintain activated ERK and Akt
      by inhibiting PP2A. We obtained evidence that PME-1 could bind and regulate
      protein phosphatase 4 (PP4), a tumor-promoting protein, but not the related
      protein phosphatase 6 (PP6). When the PP2A, PP4, or PP6 catalytic subunits were
      overexpressed, inhibiting PME-1 was sufficient to limit cell proliferation. In
      clinical specimens of endometrial adenocarcinoma, PME-1 levels were increased and
      we found that PME-1 overexpression was sufficient to drive tumor growth in a
      xenograft model of the disease. Our findings identify PME-1 as a modifier of
      malignant development and suggest its candidacy as a diagnostic marker and as a
      therapeutic target in endometrial cancer.

PMID- 24928783
TI  - Germline mutation of Bap1 accelerates development of asbestos-induced malignant
      mesothelioma.
AB  - Malignant mesotheliomas are highly aggressive tumors usually caused by exposure
      to asbestos. Germline-inactivating mutations of BAP1 predispose to mesothelioma
      and certain other cancers. However, why mesothelioma is the predominate
      malignancy in some BAP1 families and not others, and whether exposure to asbestos
      is required for development of mesothelioma in BAP1 mutation carriers are not
      known. To address these questions experimentally, we generated a Bap1(+/-)
      knockout mouse model to assess its susceptibility to mesothelioma upon chronic
      exposure to asbestos. Bap1(+/-) mice exhibited a significantly higher incidence
      of asbestos-induced mesothelioma than wild-type (WT) littermates (73% vs. 32%,
      respectively). Furthermore, mesotheliomas arose at an accelerated rate in Bap1(+/
      ) mice than in WT animals (median survival, 43 weeks vs. 55 weeks after initial
      exposure, respectively) and showed increased invasiveness and proliferation. No
      spontaneous mesotheliomas were seen in unexposed Bap1(+/-) mice followed for up
      to 87 weeks of age. Mesothelioma cells from Bap1(+/-) mice showed biallelic
      inactivation of Bap1, consistent with its proposed role as a recessive cancer
      susceptibility gene. Unlike in WT mice, mesotheliomas from Bap1(+/-) mice did not
      require homozygous loss of Cdkn2a. However, normal mesothelial cells and
      mesothelioma cells from Bap1(+/-) mice showed downregulation of Rb through a
      p16(Ink4a)-independent mechanism, suggesting that predisposition of Bap1(+/-)
      mice to mesothelioma may be facilitated, in part, by cooperation between Bap1 and
      Rb. Drawing parallels to human disease, these unbiased genetic findings indicate
      that BAP1 mutation carriers are predisposed to the tumorigenic effects of
      asbestos and suggest that high penetrance of mesothelioma requires such
      environmental exposure.

PMID- 24928784
TI  - Implications of targeted versus universal admission screening for meticillin
      resistant Staphylococcus aureus carriage in a London hospital.
AB  - Universal admission screening for meticillin-resistant Staphylococcus aureus
      (MRSA) has been performed in England since 2010. We evaluated the predictive
      performance of a regression model derived from the first year of universal
      screening for detecting MRSA at hospital admission. If we had used our previous
      targeted screening policy, 75% fewer patients (21,699 per year) would have been
      screened. However, this would have identified only ~55% of all MRSA carriers, 65%
      of healthcare-associated MRSA strains, and 40% of community-associated strains.
      Failing to identify ~45% of patients (262 per year) carrying MRSA at hospital
      admission may have implications for MRSA control.

PMID- 24928785
TI  - The epic3 recommendation that clinically indicated replacement of peripheral
      venous catheters is safe and cost-saving: how much would the NHS save?

PMID- 24928786
TI  - Free-living amoebae: what part do they play in healthcare-associated infections?
AB  - Free-living amoebae (FLA) are ubiquitous protozoa that do not require a host
      organism for survival. They are found in natural environments such as water or
      soil, and man-made environments including tap water or swimming pools, where they
      may interact with other micro-organisms, including bacteria, fungi and viruses.
      FLA can harbour micro-organisms including those found in hospital water systems,
      offering them protection against hostile conditions, providing a vehicle of
      dissemination, and enabling them to prepare for subsequent survival in
      macrophages. The interaction between Legionella pneumophila and FLA has been
      studied extensively; subsequent investigations have shown that FLA may serve as a
      reservoir for other bacteria including mycobacteria, Pseudomonas aeruginosa,
      Acinetobacter baumannii, or even fungi and viruses. Amoebae found in hospital
      water systems can serve as a reservoir of potential pathogens and thus be
      indirectly related to healthcare-associated infections.

PMID- 24928787
TI  - Outbreak of invasive group A streptococcus infection: contaminated patient
      curtains and cross-infection on an ear, nose and throat ward.
AB  - BACKGROUND: Outbreaks of group A streptococcus (GAS) infections may occur in
      healthcare settings and have been documented in surgical, obstetrics and
      gynaecology, and burns units. The environment may serve as a reservoir and
      facilitate transmission via contaminated equipment. AIM: To describe the
      investigation and control of an outbreak of healthcare-associated GAS infection
      on an ear, nose and throat (ENT) ward in a tertiary referral centre. METHODS: Two
      patients with laryngeal cancer developed invasive GAS infection (bacteraemia)
      with associated tracheostomy wound cellulitis within a 48 h period. The outbreak
      team undertook an investigation involving a retrospective review of GAS cases,
      prospective case finding, healthcare worker screening and sampling of patient
      curtains. Immediate control measures included source isolation, a thorough
      rolling clean with a chlorine-based disinfectant and hydrogen peroxide
      decontamination of patient equipment. FINDINGS: Prospective patient screening
      identified one additional patient with carriage of GAS from a tracheostomy wound
      swab. Staff screening identified one healthcare worker who acquired GAS during
      the outbreak and who subsequently developed pharyngitis. Environmental sampling
      demonstrated that 10 out of 34 patient curtains on the ward were contaminated
      with GAS and all isolates were typed as emm-1. CONCLUSION: This is the first
      outbreak report to demonstrate patient curtains as potential source for GAS cross
      transmission, with implications in relation to hand hygiene and frequency of
      laundering. Based on this report we recommend that during an outbreak of GAS
      infection all patient curtains should be changed as part of the enhanced
      decontamination procedures.

PMID- 24928788
TI  - Catheter-related bloodstream infection: burden of disease in a tertiary hospital.
AB  - BACKGROUND: Surveillance programmes have become the most effective tool for
      controlling catheter-related bloodstream infections (CRBSI). However, few studies
      have investigated programmes covering all hospital settings. AIM: To describe the
      results of a control and prevention programme for CRBSI based on compliance with
      recommendations for insertion and maintenance, using annual burden of disease in
      a tertiary level hospital. METHODS: A CRBSI control and prevention programme
      involving all hospital settings was implemented. The programme consisted of CRBSI
      surveillance, direct observation of insertion and maintenance of catheters to
      determine performance, and education for healthcare workers. FINDINGS: In total,
      2043 short-term catheters were inserted in 1546 patients for 18,570 catheter
      days, and 279 long-term catheters were inserted in 243 patients for 40,440
      catheter-days. The annual incidence density was 5.98 (first semester 6.40, second
      semester 5.64) CRBSI per 1000 catheter-days for short-term catheters, and 0.57
      (first semester 0.66, second semester 0.43) CRBSI per 1000 catheter-days for long
      term catheters. One hundred and forty insertion procedures were observed, with an
      average insertion time of 13 (standard deviation 7) min. Compliance with
      recommendations was as follows: hand hygiene, 86.8%; use of alcoholic
      chlorhexidine solution for skin disinfection, 35.5%; use of mask, 93.4%; use of
      gloves, 98.7%; use of gown, 75.0%; use of sterile cloth, 93.8%; use of cap,
      92.2%; bandage application, 62.7%; and use of aseptic technique, 89.5%. Forty
      five maintenance procedures were observed, and compliance rates were as follows:
      hand hygiene, 42.1%; use of gloves, 78.1%; and port disinfection with alcoholic
      chlorhexidine solution, 32.5%. CONCLUSION: The CRBSI control and prevention
      programme implemented at the study hospital has decreased the rate of CRBSI,
      provided important information about the total burden of disease, and revealed
      possible ways to improve interventions in the future.

PMID- 24928789
TI  - epic3: guidelines for preventing infections associated with the use of
      intravascular access devices.

PMID- 24928790
TI  - A novel peptide-based pan-influenza A vaccine: a double blind, randomised
      clinical trial of immunogenicity and safety.
AB  - BACKGROUND: FP-01.1 is a novel synthetic influenza A vaccine consisting of six
      fluorocarbon-modified 35-mer peptides that encapsulate multiple CD4+ and CD8+ T
      cell epitopes and is designed to induce an immune response across a broad
      population. METHODS: FP-01.1 was evaluated for safety and immunogenicity in a
      randomised, double-blind, placebo-controlled, dose-escalation, phase I clinical
      study in healthy adult volunteers (n=49). IFNgamma ELISpot assays and multicolour
      flow cytometry were used to characterise the immune response. RESULTS: FP-01.1
      was safe and well tolerated at all doses tested with a similar adverse event
      profile in actively vaccinated subjects compared with controls. Maximum
      immunogenicity was in the 150 MUg/peptide dose group where a robust response (243
      spots/million PBMC) was demonstrated in 75% subjects compared with 0% in placebo
      controls. All six peptides were immunogenic. FP-01.1 induced dual CD4+ and CD8+ T
      cell responses and vaccine-specific T cells cross-recognise divergent influenza
      strains. CONCLUSIONS: This first-in-human study showed that FP-01.1 has an
      acceptable safety and tolerability profile and generated robust anti-viral T cell
      responses in a high proportion of subjects tested. The results support the
      further clinical testing of FP-01.1 prior to clinical, proof-of-concept, live
      viral challenge studies.

PMID- 24928791
TI  - Cross-sectional study on factors associated with influenza vaccine uptake and
      pertussis vaccination status among pregnant women in Germany.
AB  - Pregnant women and their newborns are at increased risk for influenza-related
      complications; the latter also have an increased risk for pertussis-related
      complications. In Germany, seasonal influenza vaccination is recommended for
      pregnant women since 2010. A dose of pertussis-containing vaccine has been
      recommended since 2004 for women of childbearing age if they have not been
      vaccinated within the past 10 years. We conducted a nationwide cross-sectional
      survey among pregnant women in February/March 2013 to assess knowledge,
      attitudes, and practices related to influenza vaccination during pregnancy and to
      identify factors associated with their pertussis vaccination status. In total,
      1025 pregnant women participated and provided information through a self
      administered questionnaire. Of these, 23.2% were vaccinated against seasonal
      influenza during the 2012/13 season; 15.9% during their pregnancy. Major reasons
      for being unvaccinated (n=686 respondents) were lack of confidence in the vaccine
      (60.4%) and the perception that vaccination was not necessary (40.3%). Influenza
      vaccination during pregnancy was independently associated with having received
      influenza vaccine in the previous season, having received a recommendation from a
      physician, a high level of vaccine-related knowledge and of perceived disease
      severity. In contrast, knowledge of the recommendation for regular hand-washing
      to prevent influenza and the perception that vaccine-related side effects were
      likely to occur or likely to be severe were negatively associated with vaccine
      uptake. Receipt of a pertussis vaccine in the past 10 years was reported by 22.5%
      of participants. Pertussis vaccine uptake was independently associated with
      living in the Eastern federal states and receiving seasonal influenza vaccination
      annually, while a migration background was associated with a lower uptake. To
      enhance vaccine uptake in pregnant women and women of childbearing age, special
      efforts must be undertaken to improve knowledge of both recommendations and the
      benefits of vaccination. Gynecologists could serve as important facilitators. 

PMID- 24928793
TI  - Dietary supplementation with long chain polyunsaturated fatty acids in pregnant
      guinea pigs has sex-dependent effects on growth and bone outcomes in offspring.
AB  - Long chain PUFA enhance bone mass in non-pregnant mammals. We examined the
      effects of arachidonic (AA; 20:4n-6) and docosahexaenoic (DHA; 22:6n-3) acid on
      bone mass of mothers and neonates. Guinea pig sows (n=15) were fed control, DHA
      or AA+DHA diets from mating to weaning. Measurements included: osteocalcin (OC),
      deoxypyridinoline (DPD), areal bone mineral density (aBMD) in sows and neonates;
      and volumetric density (vBMD) in neonates. Only vertebral aBMD and OC:DPD ratio
      declined during reproduction and only DHA reduced OC:DPD. Male pup weight was
      reduced by DHA and female weight elevated by AA+DHA. Whole body and femur aBMD
      were reduced by DHA and AA+DHA; whereas tibia vBMD was reduced by DHA in males.
      Female whole body, tibia and vertebrae aBMD plus tibia vBMD were elevated by
      AA+DHA; and DHA elevated whole body, tibia and vertebrae aBMD. Dietary AA+DHA and
      DHA elicit sex-dependent effects on neonatal bone, with minimal impact on
      mothers. 

PMID- 24928792
TI  - Chronic intermittent ethanol exposure during adolescence: effects on social
      behavior and ethanol sensitivity in adulthood.
AB  - This study assessed long-lasting consequences of repeated ethanol exposure during
      two different periods of adolescence on 1) baseline levels of social
      investigation, play fighting, and social preference and 2) sensitivity to the
      social consequences of acute ethanol challenge. Adult male and female Sprague
      Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg
      intragastrically [i.g.], every other day for a total of 11 exposures) in a
      modified social interaction test. Early-mid adolescent intermittent exposure (e
      AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent
      intermittent exposure (l-AIE) was conducted between P45 and P65. Significant
      decreases in social investigation and social preference were evident in adult
      male rats, but not their female counterparts following e-AIE, whereas neither
      males nor females demonstrated these alterations following l-AIE. In contrast,
      both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol
      challenge in males tested 25 days after adolescent exposure. Ethanol-induced
      facilitation of social investigation and play fighting, reminiscent of that
      normally seen during adolescence, was evident in adult males after e-AIE, whereas
      control males showed an age-typical inhibition of social behavior. Males after l
      AIE were found to be insensitive to the socially suppressing effects of acute
      ethanol challenge, suggesting the development of chronic tolerance in these
      animals. In contrast, females showed little evidence for alterations in
      sensitivity to acute ethanol challenge following either early or late AIE. The
      results of the present study demonstrate a particular vulnerability of young
      adolescent males to long-lasting detrimental effects of repeated ethanol.
      Retention of adolescent-typical sensitivity to the socially facilitating effects
      of ethanol could potentially make ethanol especially appealing to these males,
      therefore promoting relatively high levels of ethanol intake later in life.

PMID- 24928794
TI  - Altered maternal proportions of long chain polyunsaturated fatty acids and their
      transport leads to disturbed fetal stores in preeclampsia.
AB  - Our previous cross-sectional studies have shown altered proportions of long chain
      polyunsaturated fatty acids (LCPUFA) in preeclampsia (PE) at the end of pregnancy
      when the pathology has already progressed. The present longitudinal study for the
      first time reports fatty acid proportions from 16th week of gestation till
      delivery and placental transport in PE. This is a hospital based study where
      women were recruited in early pregnancy. Maternal blood was collected at 3 time
      points i.e. T1=16-20th week, T2=26-30th week and T3=at delivery. Cord blood and
      placenta were collected at delivery. This study reports data on 140 normotensive
      control (NC) and 54 PE women. In PE we report lower proportions of DHA in
      maternal plasma at T1, cord plasma and placenta (p<0.05 for all). The mRNA levels
      of placental ?5 desaturase, fatty acid transport proteins -1, -4, were lower
      (p<0.05 for all) in PE. There was also a positive association between cord and
      maternal plasma DHA and total omega-3 fatty acids at T1. This study demonstrates
      that women with PE have lower fatty acids stores at 16-20th week of gestation and
      lower placental synthesis and transport. It is likely that supplementation of
      omega-3 fatty acids during the 16-20th week of gestation may help in improving
      fatty acid status in infants born to mothers with PE. 

PMID- 24928796
TI  - The effect of oxybutynin on cardiac autonomic modulation in healthy subjects.
AB  - PURPOSE: The aim of this study was to assess the various doses of oral oxybutynin
      on cardiac autonomic modulation by measuring short-term heart rate variability
      (HRV) indexes during supine rest position. METHODS: Eight male healthy subjects
      (20-23 years) participated in the double-blind crossover randomized study. The
      single dose of oxybutynin (2.5, 5 and 10 mg) or placebo was given to the
      volunteers in four sessions within 5-day intervals. Before and minutes of 30, 60,
      90 and 120 after administration, lead II electrocardiogram (ECG) was recorded for
      5 min. ECG extracted RR intervals data became the base of the calculation of time
      domain and frequency domain HRV parameters, which indicate cardiac autonomic
      activity. Statistical analysis was done by using the nonparametric Wilcoxon and
      Kruskal-Wallis tests. RESULTS: The data analysis has revealed that MNN (P <
      0.001), SDNN (P < 0.05), PNN50% (P < 0.01), RMSSD (P < 0.001), HFnu (P < 0.05)
      and LF/HF ratio (P < 0.05) values were significantly increased relative to
      baseline at various time points in all the groups except in placebo group. LFnu
      (P < 0.05) values were significantly increased relative to baseline at various
      time points in all the groups except in placebo group. CONCLUSIONS: Our findings
      have revealed that acute consumption of 2.5, 5 and 10 mg oxybutynin (an
      anticholinergic compound) in the juvenile healthy male subjects produces a
      cholinergic effect according to time and frequency domain of HRV indexes.

PMID- 24928798
TI  - [Not Available].

PMID- 24928799
TI  - [Not Available].

PMID- 24928800
TI  - [Not Available].

PMID- 24928797
TI  - Novel therapeutic approaches in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic, adult onset, relentlessly
      progressive neurodegenerative disease characterized by autonomic abnormalities
      associated with parkinsonism, cerebellar dysfunction, pyramidal signs, or
      combinations thereof. Treatments that can halt or reverse the progression of MSA
      have not yet been identified. MSA is neuropathologically defined by the presence
      of alpha-synuclein-containing inclusions, particularly in the cytoplasm of
      oligodendrocytes (glial cytoplasmic inclusions, GCIs), which are associated with
      neurodegeneration. The mechanisms by which oligodendrocytic alpha-synuclein
      inclusions cause neuronal death in MSA are not completely understood. The MSA
      neurodegenerative process likely comprises cell-to-cell transmission of alpha
      synuclein in a prion-like manner, alpha-synuclein aggregation, increased
      oxidative stress, abnormal expression of tubulin proteins, decreased expression
      of neurotrophic factors, excitotoxicity and microglial activation, and
      neuroinflammation. In an attempt to block each of these pathogenic mechanisms,
      several pharmacologic approaches have been tried and shown to exert
      neuroprotective effects in transgenic mouse or cellular models of MSA. These
      include sertraline, paroxetine, and lithium, which hamper arrival of alpha
      synuclein to oligodendroglia; rifampicin, lithium, and non-steroidal anti
      inflammatory drugs, which inhibit alpha-synuclein aggregation in
      oligodendrocytes; riluzole, rasagiline, fluoxetine and mesenchymal stem cells,
      which exert neuroprotective actions; and minocycline and intravenous
      immunoglobulins, which reduce neuroinflammation and microglial activation. These
      and other potential therapeutic strategies for MSA are summarized in this review.

PMID- 24928801
TI  - [Not Available].

PMID- 24928802
TI  - Efficacy of a CO2-releasing suppository in dyschezia: a double-blind, randomized,
      placebo-controlled clinical trial.
AB  - BACKGROUND: Constipation has a significant impact on quality of life. Aim of this
      study was to evaluate the safety and the efficacy for relieving dyschezia
      symptoms of a CO2-releasing suppository in a randomized, placebo-controlled,
      clinical trial. METHODS: Fifty-three office-based primary care physicians and 24
      gastroenterologists conducted the study in France, between November 2010 and
      January 2012. Patients (aged 18-75 years) with dyschezia were eligible. Patients
      were randomly allocated a once-a-day suppository (CO2-releasing suppository or
      placebo) for 21 days. Primary endpoint was the change, from Day 0 to Day 21, in
      the intensity of discomfort related to dyschezia based on a self-assessed 0-100
      visual analogue scale. RESULTS: A total of 323 patients were randomized, i.e. 166
      into the intervention group and 157 into the placebo group. Co-variance analysis
      showed a greater reduction in discomfort visual analogue scale score in the
      intervention group (-34.5mm; standard error of the mean: 1.8mm) than in the
      placebo group (-26.2mm; standard error of the mean: 1.9 mm; p<0.001). The greater
      efficacy of the CO2-releasing suppository was confirmed for all secondary
      efficacy parameters. No significant side effects for either treatment were
      observed. CONCLUSION: A CO2-releasing suppository is more effective than a
      placebo for the relief of symptoms of dyschezia. This efficacy is associated with
      a good safety profile.

PMID- 24928803
TI  - Early policy responses to the human papillomavirus vaccine in the United States,
      2006-2010.
AB  - PURPOSE: To examine the policies state governments pursued and enacted across the
      United States in the 5-year period after the U.S. Food and Drug Administration
      licensed the human papillomavirus (HPV) vaccine in 2006, including the timing and
      number of bills introduced, the policies proposed, and the legislative success of
      HPV vaccine policy proposals. METHODS: Content abstraction and analysis of state
      level HPV vaccine-related bills across the 50 states and the District of Columbia
      introduced between 2006 and 2010. RESULTS: All but five states (Alaska, Delaware,
      Idaho, New Hampshire, and Wyoming) introduced HPV vaccine bills between 2006 and
      2010. Two-thirds of all bills were introduced in 2007. In all, 141 bills were
      introduced and 23% or 32 bills were enacted. Of the bills that were enacted,
      43.8% provided information for parents and schools about the vaccine; 37.5%
      provided public financing for HPV vaccines; 34.4% were classified as other
      policies; 25% created awareness campaigns; 25% required private insurance
      coverage of the HPV vaccination; 12.5% included voluntary vaccination, and 9.4%
      mandated vaccination for school entry. One bill reversed prior mandatory
      vaccination policies. Overall, 91% of enacted HPV vaccine bills did not refer to
      mandated vaccinations but adopted alternate policy strategies in response to the
      availability of the new HPV vaccine. CONCLUSIONS: Nationwide, states responded to
      the new HPV vaccine by introducing policies designed to increase the availability
      of information about the vaccine, provide funding, and regulate private insurance
      coverage rather than require vaccination for school entry.

PMID- 24928804
TI  - School sport participation during adolescence and mental health in early
      adulthood.
AB  - PURPOSE: This longitudinal study examined the association between participation
      in school sport during adolescence and mental health in early adulthood. METHODS:
      Adolescents (n = 853) reported participation in school sport in each grade
      throughout the 5 years of secondary school. In early adulthood, participants
      reported depressive symptoms, level of stress, and self-rated mental health.
      RESULTS: Involvement in school sport during adolescence was a statistically
      significant predictor of lower depression symptoms, lower perceived stress, and
      higher self-rated mental health in young adulthood. CONCLUSIONS: School sport
      participation may protect against poor mental health in early adulthood. Policies
      to increase school sport participation may be warranted as part of public health
      strategies to promote mental health.

PMID- 24928807
TI  - WHO and the media: a major impediment to global health?

PMID- 24928806
TI  - Initiating dopaminergic treatment in Parkinson's disease.

PMID- 24928808
TI  - Gene expression profiling of Drosophila tracheal fusion cells.
AB  - The Drosophila trachea is a premier genetic system to investigate the fundamental
      mechanisms of tubular organ formation. Tracheal fusion cells lead the branch
      fusion process to form an interconnected tubular network. Therefore, fusion cells
      in the Drosophila trachea will be an excellent model to study branch fusion in
      mammalian tubular organs, such as kidneys and blood vessels. The fusion process
      is a dynamic cellular process involving cell migration, adhesion, vesicle
      trafficking, cytoskeleton rearrangement, and membrane fusion. To understand how
      these cellular events are coordinated, we initiated the critical step to assemble
      a gene expression profile of fusion cells. For this study, we analyzed the
      expression of 234 potential tracheal-expressed genes in fusion cells during
      fusion cell development. 143 Tracheal genes were found to encode transcription
      factors, signal proteins, cytoskeleton and matrix proteins, transporters, and
      proteins with unknown function. These genes were divided into four subgroups
      based on their levels of expression in fusion cells compared to neighboring non
      fusion cells revealed by in situ hybridization: (1) genes that have relative high
      abundance in fusion cells, (2) genes that are dynamically expressed in fusion
      cells, (3) genes that have relative low abundance in fusion cells, and (4) genes
      that are expressed at similar levels in fusion cells and non-fusion tracheal
      cells. This study identifies the expression profile of fusion cells and
      hypothetically suggests genes which are necessary for the fusion process and
      which play roles in distinct stages of fusion, as indicated by the location and
      timing of expression. These data will provide the basis for a comprehensive
      understanding of the molecular and cellular mechanisms of branch fusion. 

PMID- 24928809
TI  - Expression pattern of class I phosphoinositide 3-kinase and distribution of its
      product, phosphatidylinositol-3,4,5-trisphosphate, during Drosophila
      embryogenesis.
AB  - The class I phosphoinositide 3-kinase (PI3K) can be activated by a large variety
      of extracellular stimuli and is responsible for generating phosphatidylinositol
      3,4,5-trisphosphate (PI(3,4,5)P(3)) from phosphatidylinositol-4,5-bisphosphate at
      the plasma membrane. The expression pattern of the class I PI3K and distribution
      of PI(3,4,5)P(3), visualized by its specific binding protein, GRP1-PH, were
      examined during Drosophila embryogenesis. We found that the RNA of Pi3K21B,
      encoding the Drosophila p60 regulatory subunit of the class I PI3Ks, was
      expressed maternally and expressed primarily in pole cells after cellularization
      until completion of germ band elongation. The RNA of Pi3K92E, encoding the
      Drosophila p110 catalytic subunit of the class I PI3Ks, was also expressed
      maternally. During gastrulation, its transcript level became lower and was
      slightly enriched in invaginating cells. Both Pi3K21B and Pi3K92E were expressed
      ubiquitously after germ band elongation and persisted during germ band
      shortening. PI(3,4,5)P(3) was distributed at the apical region of the
      invaginating cells during gastrulation. These findings suggest a possible
      involvement of class I PI3K and PI(3,4,5)P(3) in the regulation of invagination
      during gastrulation.

PMID- 24928810
TI  - Verification of surface wave solutions obtained by the reciprocity theorem.
AB  - Surface wave motions generated by a time-harmonic point load applied at the
      surface of an isotropic linearly elastic half-space are conventionally solved by
      the use of integral transform techniques. The inverse transforms, are often
      complicated and will not always yield closed-form solutions. In this paper
      expressions for the displacements for surface wave motions radiated from point
      load excitation are determined in a simple manner by the use of the elastodynamic
      reciprocity theorem. It is shown that the radiated amplitudes of the surface
      displacements obtained by the reciprocity approach are identical to the
      corresponding results obtained by the use of Hankel transform and by Lamb in his
      classical paper. 

PMID- 24928811
TI  - Efficacy of lower-limb muscle training modalities in severely dyspnoeic
      individuals with COPD and quadriceps muscle weakness: response from the authors.

PMID- 24928813
TI  - A UK-based resource to support the monitoring and safe use of anti-TB drugs and
      second-line treatment of multidrug-resistant TB.
AB  - Using the best available evidence and expert consensus, this document provides
      guidance for adverse effect monitoring in multidrug-resistant TB (MDR-TB). It
      includes recommendations for baseline tests, routine drug and toxicity monitoring
      guides as well as individual drug monographs for all drugs currently available in
      the UK to treat TB. These recommendations provide a structure through which
      healthcare professionals can better manage the complex drug regimens required for
      the treatment of MDR-TB; minimising the risk of adverse incidents and helping to
      improve patients' tolerance, compliance and treatment completion. 

PMID- 24928812
TI  - Comparison of spatially matched airways reveals thinner airway walls in COPD. The
      Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations
      and Intermediate Outcomes in COPD Study (SPIROMICS).
AB  - BACKGROUND: COPD is characterised by reduced airway lumen dimensions and fewer
      peripheral airways. Most studies of airway properties sample airways based upon
      lumen dimension or at random, which may bias comparisons given reduced airway
      lumen dimensions and number in COPD. We sought to compare central airway wall
      dimensions on CT in COPD and controls using spatially matched airways, thereby
      avoiding selection bias of airways in the lung. METHODS: The Multi-Ethnic Study
      of Atherosclerosis (MESA) COPD Study and Subpopulations and Intermediate Outcomes
      in COPD Study (SPIROMICS) recruited smokers with COPD and controls aged 50-79
      years and 40-80 years, respectively. COPD was defined by current guidelines.
      Using CT image data, airway dimensions were measured for all central airway
      segments (generations 0-6) following 5 standardised paths into the lungs. Case
      control airway comparisons were spatially matched by generation and adjusted for
      demographics, body size, smoking, CT dose, per cent emphysema, airway length and
      lung volume. RESULTS: Among 311 MESA COPD participants, airway wall areas at
      generations 3-6 were smaller in COPD compared with controls (all p<0.001). Among
      1248 SPIROMICS participants, airway wall areas at generations 1-6 were smaller
      (all p<0.001), and this reduction was monotonic with increasing COPD severity
      (p<0.001). In both studies, sampling airways by lumen diameter or randomly
      resulted in a comparison of more proximal airways in COPD to more peripheral
      airways in controls (p<0.001) resulting in the appearance of thicker walls in
      COPD (p<0.02). CONCLUSIONS: Airway walls are thinner in COPD when comparing
      spatially matched central airways. Other approaches to airway sampling result in
      comparisons of more proximal to more distal airways and potentially biased
      assessment of airway properties in COPD.

PMID- 24928814
TI  - Trials of home mechanical ventilation in COPD: what have we learnt?

PMID- 24928815
TI  - Inferior quality of care and outcomes for acute coronary syndrome with left
      anterior hemiblock.

PMID- 24928816
TI  - The gift of failure: learning to provide better cardiac care.

PMID- 24928805
TI  - Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors
      compared with levodopa as initial treatment for Parkinson's disease (PD MED): a
      large, open-label, pragmatic randomised trial.
AB  - BACKGROUND: Whether initial treatment for Parkinson's disease should consist of
      levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is
      uncertain. We aimed to establish which of these three classes of drug, as initial
      treatment, provides the most effective long-term control of symptoms and best
      quality of life for people with early Parkinson's disease. METHODS: In this
      pragmatic, open-label randomised trial, patients newly diagnosed with Parkinson's
      disease were randomly assigned (by telephone call to a central office; 1:1:1)
      between levodopa-sparing therapy (dopamine agonists or MAOBI) and levodopa alone.
      Patients and investigators were not masked to group assignment. Primary outcomes
      were the mobility dimension on the 39-item patient-rated Parkinson's disease
      questionnaire (PDQ-39) quality-of-life scale (range 0-100 with six points defined
      as the minimally important difference) and cost-effectiveness. Analysis was
      intention to treat. This trial is registered, number ISRCTN69812316. FINDINGS:
      Between Nov 9, 2000, and Dec 22, 2009, 1620 patients were assigned to study
      groups (528 to levodopa, 632 to dopamine agonist, 460 to MAOBI). With 3-year
      median follow-up, PDQ-39 mobility scores averaged 1.8 points (95% CI 0.5-3.0,
      p=0.005) better in patients randomly assigned to levodopa than those assigned to
      levodopa-sparing therapy, with no increase or attrition of benefit during 7
      years' observation. PDQ-39 mobility scores were 1.4 points (95% CI 0.0-2.9,
      p=0.05) better in patients allocated MAOBI than in those allocated dopamine
      agonists. EQ-5D utility scores averaged 0.03 (95% CI 0.01-0.05; p=0.0002) better
      with levodopa than with levodopa-sparing therapy; rates of dementia (hazard ratio
      [HR] 0.81, 95% CI 0.61-1.08, p=0.14), admissions to institutions (0.86, 0.63
      1.18; p=0.4), and death (0.85, 0.69-1.06, p=0.17) were not significantly
      different, but the upper CIs precluded any substantial increase with levodopa
      compared with levodopa-sparing therapy. 179 (28%) of 632 patients allocated
      dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued
      allocated treatment because of side-effects compared with 11 (2%) of 528 patients
      allocated levodopa (p<0.0001). INTERPRETATION: Very small but persistent benefits
      are shown for patient-rated mobility scores when treatment is initiated with
      levodopa compared with levodopa-sparing therapy. MAOBI as initial levodopa
      sparing therapy was at least as effective as dopamine agonists. FUNDING: UK
      National Institute for Health Research Health Technology Assessment Programme and
      UK Department of Health.

PMID- 24928817
TI  - Developing CIRCA-BC and exploring the role of the computer as a third participant
      in conversation.
AB  - The Computer Interactive Reminiscence Conversation Aid (CIRCA) is a software
      program using touch screen technology and digital materials from public archives
      to support conversation between people with dementia and their carers. In this 2
      phase study, we first worked with seniors' focus groups to identify and select
      relevant content for a regional adaptation of CIRCA (British Columbia version of
      CIRCA [CIRCA-BC]). We then pilot tested CIRCA-BC with 3 participants having
      dementia and a conversation partner, analyzing their interactions to explore how
      they drew on program content and format to shape their conversations together.
      Findings provide insight into, first, how participants' shared and distinct
      social histories influence reminiscence-based conversations and, second, how the
      computer can be viewed as a third "participant" in the interaction. These
      findings offer guidelines for ongoing adaptation and application of the CIRCA
      program in addition to contributing further evidence regarding the role of
      technology in facilitating meaningful interaction between people with dementia
      and their carers. 

PMID- 24928818
TI  - The value and underutilization of simple reading glasses in geropsychiatry
      inpatient settings.
AB  - For almost everyone, the need for reading glasses is an inevitable part of the
      second half of life. Forgetting one's reading glasses at a restaurant can be a
      disturbing reminder of one's dependence on them. For geriatric inpatients,
      however, the value of reading glasses in improving quality of life and preventing
      delirium may be overlooked. Subsequently, the authors present a brief review of
      visual impairment, the relationship of visual impairment and cognition and the
      cost of reading glass, and the results of a survey that was conducted to
      determine the proportion of inpatient geriatric psychiatry inpatient units in the
      United States, which provide reading glasses to inpatients as well as to assess
      the knowledge of medical directors of these units regarding the cost and
      perceived value of providing reading glasses to hospitalized patients.

PMID- 24928819
TI  - Utility of the cognitive difficulties scale and association with objective test
      performance.
AB  - Subjective memory complaints (SMCs) are commonly noted in memory disorder clinic
      patients. The present study sought to examine the presence of SMCs on the
      Cognitive Difficulties Scale (CDS) in older adults and to examine the
      relationship between CDS scores and current cognitive ability. Participants were
      50 adults diagnosed with possible/probable Alzheimer's disease (AD), 100 with
      amnestic mild cognitive impairment (MCI) and 84 cognitively healthy controls
      (HCs). Participants completed a neuropsychological evaluation and the self- and
      informant-reported CDS. Results indicated that greater self-reported SMCs were
      noted in the group with MCI ; however, self-reported CDS scores were associated
      with cognition in HCs only. Informant-reported CDS scores were predictive of
      cognitive ability in the diagnosis of MCI but not AD, indicating the importance
      of obtaining caregiver report in the evaluation of memory disorders. As AD is a
      neurodegenerative disorder, SMCs lose value in determining degree of cognitive
      impairment as disease stage increases.

PMID- 24928820
TI  - Cognitive impairment among elderly individuals in Shanghai suburb, China:
      association of C-reactive protein and its interactions with other relevant
      factors.
AB  - OBJECTIVES: To investigate the association between serum C-reactive protein (CRP)
      concentration and cognitive impairment as well as interactions between CRP and
      other relevant factors. METHODS: Patients with cognitive impairment and 1 to 2
      age- and sex-matched controls nested from a population-based study among
      residents aged 60 years and older in Shanghai suburb. The associations of serum
      CRP concentration and other relevant factors were examined with logistic
      regression analysis. RESULTS: The mean CRP in patients with cognitive impairment
      was higher than that in controls (P < .001). The highest quartile of CRP (>4.77
      mg/L), abdomen obesity, hypertriglyceridemia, and hyperglycemia was associated
      with cognitive impairment. Significant interactions were found between increased
      CRP and hypertriglyceridemia as well as between increased CRP and hyperglycemia
      on cognitive impairment; and the attributable proportion due to interaction was
      82% (P < .0001) and 37% (P = .007), respectively. CONCLUSIONS: Increased CRP was
      associated with cognitive impairment, and additive effects of increased CRP with
      hypertriglyceridemia and hyperglycemia on cognitive impairment were observed
      among elderly individuals.

PMID- 24928821
TI  - Hypointense signal lesions of the articular cartilage: a review of current
      concepts.
AB  - Discussion of articular cartilage disease detection by MRI usually focuses on the
      presence of bright signal on T2-weighted sequences, such as in Grade 1
      chondromalacia and cartilage fissures containing fluid. Less emphasis has been
      placed on how cartilage disease may be manifested by dark signal on T2-weighted
      sequences. The appearance of the recently described "cartilage black line sign"
      of the femoral trochlea highlights these lesions and further raises the question
      of their etiology. We illustrate various hypointense signal lesions that are not
      restricted to the femoral trochlea of the knee joint and discuss the possible
      etiologies for these lesions. 

PMID- 24928822
TI  - Is any landmark reliable in vertebral enumeration? A study of 3.0-Tesla lumbar
      MRI comparing skeletal, neural, and vascular markers.
AB  - PURPOSE: This study aimed to determine the reliability of the iliolumbar ligament
      (ILL), 12th costa, aortic bifurcation (AB), right renal artery (RRA), and conus
      medullaris (CM) for numbering of vertebral segments. SUBJECTS AND METHODS: Five
      hundred five patients underwent routine lumbar MRI examinations including a
      cervicothoracic sagittal scout and T1 and T2-weighted sagittal and axial turbo
      spin echo images. Images were evaluated by two radiologists separately. RESULTS:
      The identifiability of ILL and 12th costa were 85.7% and 48.1%. AB, RRA, and CM
      were located more caudally in lumbarized S1 and more cranially in sacralized L5
      cases. CONCLUSION: Landmarks suggested by previous studies are not reliable
      alternatives to cervicothoracic scout images due to wide ranges of distribution
      and inconsistencies in identification.

PMID- 24928823
TI  - Clinical consequences of an indeterminate CT pulmonary angiogram in cancer
      patients.
AB  - Our aim was to evaluate clinical management and outcomes in cancer patients who
      had an indeterminate Computed Tomographic Pulmonary Angiogram (CTPA) for the
      assessment of pulmonary embolus. We reviewed 1000 CTPA studies and identified 251
      limited (indeterminate) CTPA. We examined follow-up imaging and reviewed clinical
      management decisions and any positive diagnosis of venous thromboembolic disease
      (VTE) within the subsequent 90 days. 60 patients (23.9%) had a follow-up imaging
      study within five days. 8 had a positive study for VTE disease within 5 days. 3
      patients (1.2%) were placed on anticoagulation therapy based on the limited CT
      result.

PMID- 24928824
TI  - Medicinal plants used in malaria treatment by Prometra herbalists in Uganda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aim of the survey was to document medicinal
      plants used in malaria treatment by Prometra (Promocion de la medicina
      tradicional amazonica) Traditional Medical Practitioners (TMPs) of Uganda and for
      search of new antiplasmodial herbal medicines (HMs) for further phytochemical
      analysis. MATERIALS AND METHODS: In this study, semi structured guided open and
      close ended questionnaires were used. Focus group discussions were conducted and
      key informants were chosen within the TMPs who helped in further discussions of
      how the herbal remedies where collected, prepared and administered. RESULTS: A
      sample size of 51 respondents was randomly selected among the TMPs with the help
      of their leader. 86 species distributed over 81 genera and 39 families were
      reportedly being used as herbal remedies in malaria treatment. The TMPs use
      symptoms like high temperature, shivering, among others in malaria diagnosis an
      indication that they understand malaria. They emphasized the use of leaves and
      bark in treatment because they can regenerate and therefore ensure sustainable
      use of plants rather than the use of roots which would be destructive. These TMPS
      treat and also advise their patients on preventive measures against malaria
      attacks like sleeping under mosquito nets, clearing bushes near homesteads, among
      others which is an indication that they help in the prevention and mitigation of
      malaria incidences and prevalence in the areas where they live. The Informant
      Consensus Factor (FIC) value of 0.8 demonstrated that the TMPs of Prometra-Uganda
      tend to agree with each other in terms of the plant species they use in malaria
      treatment an indication of quality control in as far as administration of the
      herbal remedies. Vernonia amygdalina Delile, Bidens pilosa L., Justicia betonica
      L. were highly cited as being used in malaria treatment with frequencies of
      mention of 38, 28 and 25, respectively. CONCLUSION: TMPs of Prometra-Uganda
      understand and treat malaria using the available plant diversity from their huge
      forest and the herbal gardens within Buyija forest. The healers are very keen at
      plant conservation which is a good practice. Species like Justica betonica may be
      investigated further for antiplasmodial assays to justify its efficacy.

PMID- 24928825
TI  - Bidirectional effects of methanol extract of Wei-Chang-An pill on
      gastrointestinal transit and the spasmolytic activity on isolated rat jejunum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Wei-Chang-An pill (WCA pill), a traditional
      Chinese medicine, has been used for treating various gastrointestinal diseases
      for several decades. Despite the popular medicinal use of WCA pill, less data was
      available to its activity and mechanism in gastrointestinal disorders. To examine
      the effects of the methanol extract of WCA pill (ME) on gastrointestinal tract so
      as to assess some of the possible mechanisms involved in the clinical treatment.
      MATERIALS AND METHODS: ME was studied on gastrointestinal transit in vivo
      including gastric emptying and small intestinal motility in normal and
      neostigmine-induced mice, as well as on the isolated tissue preparations of rat
      jejunum in vitro. RESULTS: In vivo, the gastric emptying decreased and intestinal
      transit increased after administration of ME in normal mice. However,
      administration of ME accelerated the intestinal transit ranging from 0.01 to 0.8
      mg/mL and reduced it at the concentration of 1.6 and 3.2 mg/mL, while the gastric
      emptying was inhibited throughout the concentrations in neostigmine-induced mice.
      in vitro, ME caused inhibitory effect on the spontaneous contraction of rat
      isolated jejunum in dose-dependent manner ranging from 0.01 to 6 mg/mL and also
      relaxed the acetylcholine chloride (Ach, 10(-6) M)-induced and K+ (60 mM)-induced
      contractions. ME shifted the Ca2+ concentration-response curves to right, similar
      to that caused by verapamil (0.025 mM). CONCLUSIONS: These results indicated that
      ME might play a bidirectional role in gastrointestinal transit modulation and the
      effects on isolated tissue are probably mediated through calcium influx and
      muscarinic receptors, which provides pharmacological basis for the clinical use
      of WCA pill in gastrointestinal tract disorders.

PMID- 24928826
TI  - Antinociceptive and anti-inflammatory activity of Sambucus palmensis link, an
      endemic Canary Island species.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sambucus palmensis Link is an endemic species of
      the Canary Islands, popularly known as "Sauco canario". This species has wide use
      in folk medicine practice on the islands, especially as analgesic and anti
      inflammatory. So the aim of our study is to evaluate the antinociceptive and anti
      inflammatory activity of an aqueous extract of this species. MATERIALS AND
      METHODS: Three aqueous extract doses (35, 52.5 and 70 mg/kg) were orally
      administered to laboratory Swiss mice obtained from the Central Animal House of
      La Laguna University. Writhing responses induced by phenylquinone, formalin
      induced paw pain response, tail-flick test and paw edema induced by carrageenan
      were evaluated in this work. RESULTS: Oral pretreatment with 52.5 and 70 mg/kg
      Sambucus palmensis aqueous extract significantly reduced the writhing number
      induced by phenylquinone injection (61.64 and 89.04% respectively), and the pain
      response in the first (36.67 and 38.89%) and second (57.28 and 70.1%) phases
      respectively of the formalin test. Sambucus palmensis had a very slight effect on
      tail-flick test and inhibited moderately the edema formation induced by
      carrageenan in mice. CONCLUSIONS: These data show for the first time that
      Sambucus palmensis has a significant antinociceptive effect that seems to be more
      peripherical than central. Sambucus palmensis also displays a moderate anti
      inflammatory activity in an acute inflammation model. These results support the
      widespread use of Sambucus palmensis in popular medicine to treat pain and
      inflammation.

PMID- 24928827
TI  - Inhibition of the DHT-induced PSA secretion by Verbascum xanthophoeniceum and
      Serenoa repens extracts in human LNCaP prostate epithelial cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Verbascum xanthophoeniceum is a mullein plant,
      typical of Balkan region and some parts of Turkey, traditionally used as
      phytotherapeutic agent due to its anti-inflammatory properties. It is rich in
      phenylethanoid and iridoid metabolites whose anti-inflammatory properties are
      under characterization. MATERIALS AND METHODS: The role of Verbascum
      xanthophoeniceum crude methanolic extract and its isolated phenylethanoid
      glycoside verbascoside have been evaluated, in comparison to a saw palmetto
      extract, on a human in vitro model of androgen-regulated prostate epithelium, the
      LNCaP cell line. Cytotoxicity and DHT-induced free and total PSA secretion have
      been thoroughly studied. RESULTS: We have found that similar to saw palmetto,
      Verbascum xanthophoeniceum extract and its isolated phenylethanoid glycoside
      verbascoside have no cytotoxicity in human LNCaP prostate epithelial cells,
      whereas an inhibitory effect on the DHT-induced free and total PSA secretion, a
      recognized anti-androgen like activity, has been shown in case of both Verbascum
      xanthophoeniceum extract and pure verbascoside. Furthermore, in the absence of
      the endogenous androgen DHT, an androgen-like activity in Verbascum
      xanthophoeniceum is detectable as it is for saw palmetto, suggesting that a mixed
      androgen-antiandrogen activity is present. CONCLUSIONS: For the first time,
      Serenoa repens and Verbascum xanthophoeniceum extracts have shown an absence of
      cytotoxicity and an inhibitory effect on DHT-induced PSA secretion in an in vitro
      model of human prostate epithelium, whereas the phenylethanoid glycoside
      verbascoside appeared to explain only part of the Verbascum xanthophoeniceum
      inhibitory activity on PSA secretion.

PMID- 24928828
TI  - Traditional Chinese herbs as chemical resource library for drug discovery of anti
      infective and anti-inflammatory.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Infection is a major group of diseases which
      caused significant mortality and morbidity worldwide. Traditional Chinese herbs
      have been used to treat infective diseases for thousands years. The numerous
      clinical practices in disease therapy make it a large chemical resource library
      for drug discovery. MATERIALS AND METHODS: In this study, we collected 1156 kinds
      of herbs and 22,172 traditional Chinese medicinal compounds (Tcmcs). The chemical
      informatics and network pharmacology were employed to analyze the anti-infective
      effects of herbs and Tcmcs. In order to evaluate the drug likeness of Tcmcs, the
      molecular descriptors of Tcmcs and FDA-approved drugs were calculated and the
      chemical space was constructed on the basis of principal component analysis in
      the eight descriptors. On purpose to estimate the effects of Tcmcs to the targets
      of FDA-approved anti-infective or anti-inflammatory drugs, the molecular docking
      was employed. After that, docking score weighted predictive models were used to
      predict the anti-infective or anti-inflammatory efficacy of herbs. RESULTS: The
      distribution of herbs in the phylogenetic tree showed that most herbs were
      distributed in family of Asteraceae, Fabaceae and Lamiaceae. Tcmcs were well
      coincide with drugs in chemical space, which indicated that most Tcmcs had good
      drug-likeness. The predictive models obtained good specificity and sensitivity
      with the AUC values above 0.8. At last, 389 kinds of herbs were obtained which
      were distributed in 100 families, by using the optimal cutoff values in ROC
      curves. These 389 herbs were widely used in China for treatment of infection and
      inflammation. CONCLUSION: Traditional Chinese herbs have a considerable number of
      drug-like natural products and predicted activities to the targets of approved
      drugs, which would give us an opportunity to use these herbs as a chemical
      resource library for drug discovery of anti-infective and anti-inflammatory.

PMID- 24928829
TI  - Antigenotoxic and antioxidant effects of the Mongolian medicinal plant Leptopyrum
      fumarioides (L): an in vitro study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leptopyrum fumarioides has been used in the
      traditional medicine of Mongolia for the treatment of various diseases, including
      drug intoxications. However, since there is only sparse information about its
      chemistry, active components, and pharmacological and toxicological effects, the
      major aim of the present study employing mouse lymphoma cells was to evaluate the
      genotoxic and antigenotoxic/antioxidative effects of extracts and components
      isolated from this plant. MATERIAL AND METHODS: A crude methanol extract was
      separated into three different sub-extracts: dichloromethane, n-butanol, and
      water. The major constituent of the n-butanol extract, i.e., the flavone luteolin
      7-O-glucoside and a mixture of the most abundant compounds in the dichloromethane
      sub-extract were then isolated. DNA damage was evaluated using the comet assay;
      the antioxidant activity was evaluated using the DPPH radical scavenging assay.
      RESULTS: The crude methanol extract, the dichloromethane sub-extract and the
      mixture of compounds isolated from the latter fraction, increased the level of
      DNA damage after three hours of exposure. In contrast, no increase in DNA damage
      was observed in the cells that had been exposed to the n-butanol and water sub
      extracts, or to the pure flavone. When non-DNA damaging concentrations of
      extracts and compounds were tested together with the DNA damaging agent catechol,
      all sub-extracts were found to reduce the catechol-induced DNA damage (the
      flavone was then found to be the most effective protective agent). The n-butanol
      sub-extract and the flavone were also found to have the most prominent
      antioxidative effects. CONCLUSION: Based on the results from the present study,
      components in Leptopyrum fumarioides were found to protect the DNA damage induced
      by catechol, probably by acting as potent antioxidants.

PMID- 24928830
TI  - Tacrolimus is an effective treatment for lupus nephritis in pregnancy.
AB  - Lupus nephritis during pregnancy increases morbidity and mortality for mother and
      baby. Flares are difficult to treat as many therapeutic options are teratogenic
      or fetotoxic. Steroids alone may be unable to control disease activity and are
      associated with higher rates of preterm delivery, sepsis and gestational
      diabetes. Reports of using tacrolimus to treat lupus nephritis in pregnancy are
      limited. We describe the pregnancies of nine women in whom tacrolimus was
      successfully used to treat lupus nephritis flare (six patients) or maintain
      stable disease (three patients). Introduction or dose escalation of oral steroids
      was avoided in five of the patients who developed active disease and steroid dose
      was rapidly reduced in the sixth patient. All women with disease flare attained
      partial or complete remission after starting tacrolimus. None of the women on
      maintenance treatment developed active disease. We propose tacrolimus as an
      effective adjuvant or alternative therapy to steroids for treating lupus
      nephritis flare or maintaining stable disease during pregnancy. 

PMID- 24928831
TI  - Age-specific prevalence of diagnosed systemic lupus erythematosus in Germany 2002
      and projection to 2030.
AB  - OBJECTIVE: The objective of this report is to estimate the prevalence and future
      number of cases of systemic lupus erythematosus (SLE) in Germany. METHODS: Data
      from a representative sample of all insurants from the statutory health insurance
      in Germany comprising more than 2.3 million individuals have been screened for
      SLE diagnoses. The gender- and age-specific prevalence of SLE is calculated. The
      case definition is based on at least one recorded diagnosis of SLE during 2002.
      The stratum-specific prevalence is applied to the current and the future
      population of Germany in order to estimate and predict the number of people with
      SLE until 2030. RESULTS: The overall prevalence of diagnosed SLE in 2002 was 15.4
      (95% CI: 13.1-17.9) and 55.4 (51.4, 59.8) per 100,000 in the male and female
      German population. This corresponds to an estimated 30,000 and 31,000 people with
      diagnosed SLE in 2002 and 2010, respectively. This number will slightly increase
      until 2020 and decrease thereafter. CONCLUSIONS: Compared with health insurance
      data from France, the prevalence in our data is similar. Under the assumption
      that the gender- and age-specific prevalence of SLE in Germany will not change
      considerably, the number of cases in the next two decades will change only
      slightly.

PMID- 24928832
TI  - A randomized, phase II study of afatinib versus cetuximab in metastatic or
      recurrent squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Afatinib is an oral, irreversible ErbB family blocker that has shown
      activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We
      hypothesized that the agent would have greater antitumor activity compared with
      cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma
      (HNSCC) patients, whose disease has progressed after platinum-containing therapy.
      PATIENTS AND METHODS: An open-label, randomized, phase II trial was conducted in
      43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day)
      or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse
      events (AEs) (stage I), with optional crossover (stage II). The primary end point
      was tumor shrinkage before crossover assessed by investigator (IR) and
      independent central review (ICR). RESULTS: A total of 121 patients were treated
      (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36
      respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with
      afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate
      was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable
      disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by
      IR; similar results were seen by ICR. Most common grade >=3 drug-related AEs
      (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and
      stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively.
      Patients with DRAEs leading to treatment discontinuation were 23% with afatinib
      and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3%
      with afatinib and 18.8%/18.8% with cetuximab. CONCLUSION: Afatinib showed
      antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase
      II trial, although more patients on afatinib discontinued treatment due to AEs.
      Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained
      clinical benefit in patients after crossover, suggesting a lack of cross
      resistance.

PMID- 24928833
TI  - SNPs in the transforming growth factor-beta pathway as predictors of outcome in
      advanced lung adenocarcinoma with EGFR mutations treated with gefitinib.
AB  - BACKGROUND: The aim of this study was to evaluate whether genetic variations in
      the transforming growth factor-beta (TGF-beta) pathway influenced clinical
      outcome of advanced lung adenocarcinoma with epidermal growth factor receptor
      (EGFR) mutations treated with gefitinib. PATIENTS AND METHODS: Two hundred six
      patients with advanced lung adenocarcinomas were enrolled in this study. EGFR
      mutation in these tumors was detected. Among them, 106 patients with EGFR
      mutation and 37 of 100 patients with wild type were treated with gefitinib.
      Genotype of 33 single-nucleotide polymorphisms (SNPs) from 13 genes involved in
      the TGF-beta signaling pathway was determined, and their association with
      survival time was analyzed. Univariate and multivariate analyses were carried out
      to assess the role of biological/clinical parameters in progression-free survival
      (PFS) and overall survival (OS) using Pearson's chi(2) test, log-rank test, and
      Cox proportional hazards model. RESULTS: Among SNPs analyzed, multivariate
      analysis showed the cytidylate and thymidine (CT) genotype of SMAD3: rs11632964
      was associated with a longer OS and PFS when the entire cohort of 143 patients
      were included; the association was significant in the patients with EGFR mutant
      tumors (30.8 versus 17.5 months; log-rank P = 0.020; and 20.8 versus 9.4 months;
      log-rank P = 0.001), when compared with patients with wild-type EGFR tumors. In
      patients with mutant EGFR, the CT genotype of SMAD3: rs11071938 and the
      cytidylate and cytidylate genotype of SMAD3: rs6494633 were also found to be
      associated with better PFS. Dual luciferase reporter assays showed gefitinib
      resistant PC9/G cells transfected with SMAD3: rs11632964T allelic reporter
      construct showed significantly lower luciferase activities compared with cells
      expression C allelic reporter construct. There was significantly decreased
      expression of SMAD3 and pi-SMAD3 in the PC-9/G cells compared with PC-9.
      CONCLUSIONS: Among the candidate genes involved in the TGF-beta pathway, the
      polymorphisms of SMAD3 appear to be highly predictive of outcome of patients with
      lung adenocarcinoma after gefitinib treatment, especially in those with EGFR
      mutations.

PMID- 24928835
TI  - Palliative Oncology: Denosumab.
AB  - Bone metastases cause devastating clinical complications leading patients to have
      pain, poor quality of life, loss of mobility, and autonomy. Complications from
      osseous metastases cause a big economic burden reflected by repeated admissions
      for uncontrolled symptoms. Management of symptoms associated with bone metastasis
      includes systemic analgesics, glucocorticoids, radiation (external beam radiation
      and radiopharmaceuticals), ablative techniques (radiofrequency ablation and
      cryoablation), chemotherapeutic agents, hormonal therapies, interventional
      techniques (eg, kyphoplasty), and surgical approaches. Bisphosphonates have
      become a standard therapy for bony metastasis. They bind to bone eventually
      inhibiting osteoclast action. Bisphosphonates decrease fractures when given
      routinely. Adverse effects of bisphosphonates include osteonecrosis of the jaw
      and renal insufficiency. Late last year, the Food and Drug Administration
      approved denosumab to prevent skeletal-related events (SREs) associated with
      metastatic solid tumors. This drug is a monoclonal antibody that inhibits the
      receptor activator of nuclear factor kappaB (RANK)-RANK ligand interaction.
      Clinical trials have shown superiority over bisphosphonates for the prevention of
      SREs. This article reviews the mechanism of action, pharmacology, adverse
      effects, and clinical trial evidence for this new drug. 

PMID- 24928834
TI  - Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in
      the DENSE-R-CHOP-14 trial of the DSHNHL.
AB  - BACKGROUND: To improve outcome of elderly patients with diffuse large B-cell
      lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14
      trial. PATIENTS AND METHODS: Rituximab (375 mg/m(2)) was given on days 0, 1, 4,
      8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results
      were to be compared with patients who had received the same chemotherapy in
      combination with eight 2-week applications of rituximab in RICOVER-60. RESULTS:
      One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in
      considerably higher serum levels during the first 50 days of treatment, but
      rituximab exposure time was not prolonged. Grade 3 and 4 infections were
      exceptionally high in the first 20 patients without anti-infective prophylaxis,
      but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole
      in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per
      patient; P = 0.007 and P = 0.125, respectively). Patients with international
      prognostic index = 3-5 had higher complete response/complete response unconfirmed
      rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population,
      but this did not translate into better long-term outcome, even though male hazard
      was decreased (event-free survival: from 1.5 to 1.1; progression-free survival:
      from 1.7 to 1.1; overall survival: from 1.4 to 1.0). CONCLUSIONS: Dose-dense
      rituximab achieved higher rituximab serum levels, but was not more effective than
      eight 2-week applications in the historical control population, even though minor
      improvements in poor-prognosis and male patients cannot be excluded. The
      increased, though manageable toxicity, precludes its use in routine practice. Our
      results strongly support anti-infective prophylaxis with aciclovir and
      cotrimoxazole for all patients receiving R-CHOP.

PMID- 24928836
TI  - Caregivers Confronted With the Withdrawal of Artificial Nutrition at the End of
      Life: Prevalence of and Reasons for Experienced Difficulties.
AB  - BACKGROUND: Withdrawing artificial nutrition in palliative care is an issue that
      often leads to ethical dilemmas among health care providers, despite clinical
      guidelines. OBJECTIVES: To describe the experience of health care providers
      confronted with the withdrawing of artificial nutrition at the end of life and
      identifying the factors related to the level of ethical dilemmas. METHODS: Cross
      sectional survey questionnaire of all the nurses and nurses' aides working in
      medicine, surgery, and palliative care departments of a regional hospital and who
      have already been confronted with the withdrawal of artificial nutrition.
      RESULTS: Of 818 questionnaires sent, 274 were returned (response rate 33.5%); 60%
      (163) of the care providers who responded were involved in withdrawing artificial
      nutrition at the end of life. Among these, 42 (25.8%) had always or often been
      affected with ethical dilemmas, and 97 (60%) responded that withdrawing
      artificial nutrition had always or often been preceded by a multidisciplinary
      discussion. Items significantly associated with a high level of ethical dilemmas
      were (1) existence of differences in opinion within the health care team, (2)
      lack of information regarding the indication of the withdrawal of artificial
      nutrition, (3) feeling uncomfortable with the patient and his or her relatives,
      (4) guilt, (5) feeling of abandonment of care, and (6) uneasiness. CONCLUSION:
      Health care providers seem to have a lack of information and consensus regarding
      the withdrawal of artificial nutrition at the end of life. The ethical dimension
      of withdrawing artificial nutrition in palliative care has a strong impact on
      care providers, regardless of the circumstances of the withdrawal.

PMID- 24928837
TI  - Students, Severe Illness, and Palliative Care: Results From a Pilot Study on a
      School-Based Intervention.
AB  - This study was aimed at piloting a school-based intervention on severe illness,
      within a project focused on spreading knowledge of palliative care among high
      school students (phases 0-2 Medical Research Council Framework). The intervention
      entailed the screening of a topic-related movie, 2 classroom meetings, and the
      development of a class-based multimedia production. Five classes from 5 high
      schools participated in this study, and a before-after evaluation was used to
      assess intervention feasibility and impact. Valid questionnaires were filled in
      by 84% (before) and 79% (after) of the 89 students. Concerning students'
      knowledge on palliative care, the after evaluation showed a significantly higher
      paired proportions of students reporting on "improving patient quality of life"
      and "life-threatening illness." Intervention components were deemed helpful by
      students, and positive feedback on the experience was given. 

PMID- 24928838
TI  - A Spontaneous CNV Model Provides New Tool to Understand AMD.

PMID- 24928841
TI  - A novel evidence-based detection of undiagnosed spondyloarthritis in patients
      presenting with acute anterior uveitis: the DUET (Dublin Uveitis Evaluation
      Tool).
AB  - BACKGROUND: To date, there are no formal guidelines or referral pathways for
      acute anterior uveitis (AAU) patients developed or endorsed by any international
      or national societies. The objective of our study was to develop and validate an
      assessment algorithm for referral from ophthalmologists of appropriate AAU
      patients to rheumatology that will aid the early diagnosis of the
      spondyloarthropathy (SpA). METHODS: All consecutive patients attending the
      emergency department of local ophthalmology hospital with AAU, but who did not
      have a known diagnosis of SpA, were eligible to participate in this study.
      Patients with any other known cause of AAU were excluded. Two independent cohorts
      were enrolled. Test algorithm and Dublin Uveitis Evaluation Tool (DUET) algorithm
      (revised form of test algorithm) were used in these cohorts to identify patients
      as SpA suspects and non-SpA controls, respectively. RESULTS: STUDY PHASE-1.
      ALGORITHM DEVELOPMENT COHORT (n=101): After rheumatologic evaluation of the
      entire cohort, 41.6% (n=42) had undiagnosed SpA. Our test algorithm was noted to
      have: sensitivity 100% and specificity 53.5%. Further regression analysis
      resulted in the development of the DUET algorithm which made the following
      improvements: sensitivity 95%, specificity 98%, positive likelihood ratio (LR)
      56.19, and negative LR 0.04. STUDY PHASE-2. DUET ALGORITHM VALIDATION COHORT
      (n=72): After rheumatologic evaluation of the cohort, 40% (n=29) were diagnosed
      with SpA, with the following performance of DUET algorithm-sensitivity 96%,
      specificity 97%, positive LR 41.5 and negative LR 0.03. CONCLUSIONS:
      Approximately 40% of patients presenting with idiopathic AAU have undiagnosed
      SpA. A simple to apply algorithm is described with excellent sensitivity and
      specificity.

PMID- 24928843
TI  - Gareth Thomas (9 August 1932-6 February 2014).

PMID- 24928840
TI  - Genome-wide association and functional studies identify a role for IGFBP3 in hip
      osteoarthritis.
AB  - OBJECTIVES: To identify genetic associations with hip osteoarthritis (HOA), we
      performed a meta-analysis of genome-wide association studies (GWAS) of HOA.
      METHODS: The GWAS meta-analysis included approximately 2.5 million imputed HapMap
      single nucleotide polymorphisms (SNPs). HOA cases and controls defined
      radiographically and by total hip replacement were selected from the Osteoporotic
      Fractures in Men (MrOS) Study and the Study of Osteoporotic Fractures (SOF) (654
      cases and 4697 controls, combined). Replication of genome-wide significant SNP
      associations (p <=5*10(-8)) was examined in five studies (3243 cases and 6891
      controls, combined). Functional studies were performed using in vitro models of
      chondrogenesis and osteogenesis. RESULTS: The A allele of rs788748, located 65 kb
      upstream of the IGFBP3 gene, was associated with lower HOA odds at the genome
      wide significance level in the discovery stage (OR 0.71, p=2*10(-8)). The
      association replicated in five studies (OR 0.92, p=0.020), but the joint analysis
      of discovery and replication results was not genome-wide significant (p=1*10(
      6)). In separate study populations, the rs788748 A allele was also associated
      with lower circulating IGFBP3 protein levels (p=4*10(-13)), suggesting that this
      SNP or a variant in linkage disequilibrium could be an IGFBP3 regulatory variant.
      Results from functional studies were consistent with association results.
      Chondrocyte hypertrophy, a deleterious event in OA pathogenesis, was largely
      prevented upon IGFBP3 knockdown in chondrocytes. Furthermore, IGFBP3
      overexpression induced cartilage catabolism and osteogenic differentiation.
      CONCLUSIONS: Results from GWAS and functional studies provided suggestive links
      between IGFBP3 and HOA.

PMID- 24928848
TI  - The effect of coach and player injury knowledge, attitudes and beliefs on
      adherence to the FIFA 11+ programme in female youth soccer.
AB  - BACKGROUND: Injury knowledge and beliefs influence uptake of prevention
      programmes, but the relationship between knowledge, beliefs and adherence remains
      unclear. AIM: To describe injury knowledge and beliefs among youth female soccer
      coaches and players, and to identify the relationship between these factors,
      different delivery strategies of the FIFA 11+ programme and adherence. METHODS: A
      subcohort analysis from a cluster-randomised controlled trial of 31 female soccer
      teams (coaches n=29, players (ages 13-18) n=258). Preseason and postseason
      questionnaires were used to assess knowledge and beliefs. Teams recorded FIFA 11+
      adherence during the season. RESULTS: At baseline, 62.8% (95% CI 48.4% to 77.3%)
      of coaches and 75.8% (95% CI 71.5% to 80.1%) of players considered 'inadequate
      warm-up' a risk factor for injury. There was no effect of delivery method
      (OR=1.1; 95% CI 0.8 to 1.5) or adherence (OR=1.0; 95% CI 0.9 to 1.1) on this
      belief. At baseline, 13.8% (95% CI 1.3% to 26.4%) of coaches believed a warm-up
      could prevent muscle injuries, but none believed it could prevent knee and ankle
      injuries. For players, 9.7% (95% CI 6.1% to 13.3%), 4.7% (95% CI 2.1% to 7.3%)
      and 4.7% (95% CI 2.1% to 7.3%) believed a warm-up would prevent muscle, knee and
      ankle injuries, respectively. Years of playing experience were negatively
      associated with high adherence for coaches (OR=0.93; 0.88 to 0.99) and players
      (OR=0.92; 0.85 to 0.98). CONCLUSIONS: There were gaps in injury knowledge and
      beliefs, which differed for coaches and players. Beliefs did not significantly
      affect adherence to the FIFA 11+, suggesting additional motivational factors
      should be considered.

PMID- 24928849
TI  - In vitro and in vivo activity of the low-immunogenic antimesothelin immunotoxin
      RG7787 in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies
      are needed. RG7787 is a novel low-immunogenic antimesothelin recombinant
      immunotoxin (RIT), engineered to overcome the limitations of SS1P, a RIT now in
      clinical trials. In vitro activity was evaluated on five established PDAC cell
      lines (KLM-1, AsPC-1, BxPC-3, Panc 3.014, and PK-1) and on PDAC cells directly
      established from a patient tumor (GUMC108). RG7787 had subnanomolar IC50s in most
      cell lines, and was significantly more active than SS1P in GUMC108, KLM-1, and
      Panc 3.014 cells. GUMC108 was most sensitive, with RG7787 killing >99% of the
      cells. In a subcutaneous KLM-1 xenograft mouse model, two cycles of 3 * 2.5 mg/kg
      RG7787 QOD combined with two cycles of 1 * 50 mg/kg paclitaxel induced near
      complete responses, with all tumors regressing below 5 mm(3) within 30 days after
      therapy was initiated (>95% decrease) and no significant growth increase for at
      least another 3 weeks. RG7787 alone gave limited but significant regressions and
      paclitaxel by itself arrested tumor growth. Quantifying the uptake of Alexa Fluor
      647-labeled RG7787 in tumors showed that the RIT reached only 45% of KLM-1 cells,
      accounting in part for the limited responses. Paclitaxel did not improve RG7787
      uptake, which thus cannot explain the beneficial effect of the combination
      therapy. In conclusion, RG7787 has high cytotoxic activity on PDAC cell lines as
      well as on primary patient cells. In vivo, this novel RIT gives durable near
      complete tumor responses when combined with paclitaxel. RG7787 merits further
      evaluation for the treatment of PDAC.

PMID- 24928850
TI  - Expression of the miR200 family of microRNAs in mesothelial cells suppresses the
      dissemination of ovarian cancer cells.
AB  - The TGFbeta-mediated alteration of the tumor microenvironment plays a crucial
      role in tumor progression. Mesothelial cells are the primary components of the
      tumor microenvironment for ovarian cancer cells; however, the exact role of
      TGFbeta-stimulated mesothelial cells in ovarian cancer progression remains
      uncertain. In this report, we examined the effects of TGFbeta-treated mesothelial
      cells on ovarian cancer progression. We show that TGFbeta-stimulated human
      primary mesothelial cells (HPMC) are able to promote cancer cell attachment and
      proliferation and the activation of the promoter activities of MMP-2 and MMP-9,
      which are metalloproteinases necessary for tumor invasion. Expression of the
      miR200 family was downregulated in HPMCs by TGFbeta stimulation, and restoration
      of the expression of miR200 family members in HPMCs suppressed cancer cell
      attachment and proliferation. Downregulation of the miR200 family by TGFbeta
      induced fibronectin 1 production, which promoted cancer cell attachment to HPMCs.
      Finally, we demonstrated that the delivery of the miR200s to mesothelial cells in
      mice inhibited ovarian cancer cell implantation and dissemination. Our results
      suggest that alteration of the tumor microenvironment by the miR200 family could
      be a novel therapeutic strategy for ovarian cancer treatment.

PMID- 24928851
TI  - Human umbilical cord blood-derived mesenchymal stem cells producing IL15
      eradicate established pancreatic tumor in syngeneic mice.
AB  - Mesenchymal stem cells (MSC) represent a new tool for delivery of therapeutic
      agents to cancer sites because of their strong tropism toward tumors. IL15 has
      demonstrated a potent antitumor activity in various animal models as well as
      clinical trials. However, because of its short half-life, effective therapeutic
      effects usually require a high dose, which often results in undesired side
      effects; thus, new strategies for overcoming this disadvantage are needed. In
      this study, human MSCs were isolated from umbilical cord blood as delivery
      vehicles and transduced with lentivirus vector expressing murine IL15 (MSC-IL15).
      In vitro assays of lymphocyte activation and proliferation demonstrated that IL15
      produced by MSCs was biofunctional. In syngeneic mice bearing Pan02 pancreatic
      tumors, systemic administration of MSC-IL15 significantly inhibited tumor growth
      and prolonged the survival of tumor-bearing mice, which were associated with
      tumor cell apoptosis, and natural killer (NK)- and T-cell accumulation.
      Furthermore, we confirmed that MSC-IL15 could migrate toward tumor and secreted
      IL15 in tumor-specific sites. Depletion of NK and CD8(+) T cells abolished the
      antitumor activity of MSC-IL15, suggesting that NK and CD8(+) T cells play a key
      role for MSC-IL15-mediated effect. Interestingly, cured mice after MSC-IL15
      treatment were resistant to Pan02 pancreatic tumor rechallenge, and adoptive
      transfer of lymphocytes from cured mice also could cause rejection of Pan02 tumor
      inoculation in naive mice, indicating that MSC-IL15 induced tumor-specific T-cell
      immune memory response. Overall, these data support that MSCs producing IL15
      might represent an innovative strategy for therapy of pancreatic tumor.

PMID- 24928853
TI  - Identification of fluoroquinolone-resistant extended-spectrum beta-lactamase (CTX
      M-8)-producing Escherichia coli ST224, ST2179 and ST2308 in buffalo (Bubalus
      bubalis).

PMID- 24928852
TI  - Chemogenetic evaluation of the mitotic kinesin CENP-E reveals a critical role in
      triple-negative breast cancer.
AB  - Breast cancer patients with tumors lacking the three diagnostic markers (ER, PR,
      and HER2) are classified as triple-negative (primarily basal-like) and have poor
      prognosis because there is no disease-specific therapy available. To address this
      unmet medical need, gene expression analyses using more than a thousand breast
      cancer samples were conducted, which identified elevated centromere protein E
      (CENP-E) expression in the basal-a molecular subtype relative to other subtypes.
      CENP-E, a mitotic kinesin component of the spindle assembly checkpoint, is shown
      to be induced in basal-a tumor cell lines by the mitotic spindle inhibitor drug
      docetaxel. CENP-E knockdown by inducible shRNA reduces basal-a breast cancer cell
      viability. A potent, selective CENP-E inhibitor (PF-2771) was used to define the
      contribution of CENP-E motor function to basal-like breast cancer. Mechanistic
      evaluation of PF-2771 in basal-a tumor cells links CENP-E-dependent molecular
      events (e.g., phosphorylation of histone H3 Ser-10; phospho-HH3-Ser10) to
      functional outcomes (e.g., chromosomal congression defects). Across a diverse
      panel of breast cell lines, CENP-E inhibition by PF-2771 selectively inhibits
      proliferation of basal breast cancer cell lines relative to premalignant ones and
      its response correlates with the degree of chromosomal instability.
      Pharmacokinetic-pharmacodynamic efficacy analysis in a basal-a xenograft tumor
      model shows that PF-2771 exposure is well correlated with increased phospho-HH3
      Ser10 levels and tumor growth regression. Complete tumor regression is observed
      in a patient-derived, basal-a breast cancer xenograft tumor model treated with PF
      2771. Tumor regression is also observed with PF-2771 in a taxane-resistant basal
      a model. Taken together, CENP-E may be an effective therapeutic target for
      patients with triple-negative/basal-a breast cancer.

PMID- 24928854
TI  - The efficacy of non-carbapenem antibiotics for the treatment of community-onset
      acute pyelonephritis due to extended-spectrum beta-lactamase-producing
      Escherichia coli.
AB  - OBJECTIVE: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has
      become an important cause of community-onset urinary tract infections. We aimed
      to evaluate the efficacy of non-carbapenem antibiotics for acute pyelonephritis
      (APN) due to ESBL-producing E. coli. METHODS: We conducted a retrospective cohort
      study of patients with community-onset APN due to ESBL-producing E. coli at a
      single centre in Korea from 2007 to 2013. Outcomes included both microbiological
      and clinical failure. To adjust for non-random assignment of antibiotics, the
      propensity score method of inverse probability of treatment weighting and a
      multivariable analysis using Cox proportional hazards modelling were employed to
      estimate the efficacy of non-carbapenem antibiotics as compared with carbapenems.
      RESULTS: Of 152 eligible patients, 85 (55.9%) received carbapenems and 67 (44.1%)
      received non-carbapenems. Non-carbapenem antibiotics used in this cohort included
      aminoglycosides (n = 30), beta-lactam/beta-lactamase inhibitors (n = 13),
      fluoroquinolones (n = 12) and trimethoprim/sulfamethoxazole (n = 5).
      Microbiological failure was observed in 16 patients receiving carbapenems (16/83,
      19.3%) versus 4 patients receiving non-carbapenem (4/67, 6.0%). After weighting,
      the risk of microbiological failure was similar between the two groups [weighted
      hazard ratio (HR) 0.99; 95% CI 0.31-3.19]. In a multivariable regression analysis
      combined with weights, the estimate did not change (weighted adjusted HR 0.96;
      95% CI 0.41-2.27). The clinical failure rate was also similar in the two groups
      (weighted HR 1.05; 95% CI 0.24-4.62). CONCLUSIONS: These results suggest that non
      carbapenem antibiotics were as effective as carbapenems as definitive therapy for
      treating community-onset APN caused by ESBL-producing E. coli if they are active
      in vitro.

PMID- 24928855
TI  - Characterization of pFOX-7a, a conjugative IncL/M plasmid encoding the FOX-7 AmpC
      type beta-lactamase, involved in a large outbreak in a neonatal intensive care
      unit.
AB  - OBJECTIVES: FOX-type enzymes are a lineage of AmpC-type beta-lactamases from
      Aeromonas spp. whose genes have been mobilized to plasmids spreading among
      Enterobacteriaceae, where they can be responsible for resistance to extended
      spectrum cephalosporins and beta-lactamase inhibitor combinations. Little is
      known about the genetic context and plasmid vehicles of bla(FOX) determinants.
      Here, we have characterized a plasmid encoding the FOX-7 beta-lactamase, which
      was involved in a large outbreak caused by two Klebsiella pneumoniae clones in a
      neonatal intensive care unit. METHODS: Plasmid transferability was tested in
      conjugation experiments using Escherichia coli recipients. Plasmids from
      different strains were compared by restriction profiling and PCR mapping. The
      complete sequence of pFOX-7a plasmid was determined by a next-generation
      sequencing approach followed by gap filling using PCR and sequencing. RESULTS: An
      apparently identical conjugative plasmid encoding FOX-7 was detected in
      representatives of the K. pneumoniae clones that caused the outbreak and in
      sporadic FOX-7-producing strains of other species from the same ward. The
      plasmid, named pFOX-7a, has an IncL/M-type backbone and two separate resistance
      modules including a Tn3-like transposon and a novel Tn1696 derivative, named
      Tn6234, which carries an integron platform, a hybrid (but still functional)
      mercury resistance module and a novel putative transposon of original structure,
      named Tn6240, associated with the bla(FOX-7) gene. CONCLUSIONS: pFOX-7a is the
      first completely characterized plasmid encoding a FOX-type beta-lactamase. The
      bla(FOX-7) gene was associated with a putative transposable element of original
      structure, which was likely involved in its mobilization from the Aeromonas
      metagenome.

PMID- 24928856
TI  - Detection of mecC methicillin-resistant Staphylococcus aureus with a semi
      selective enrichment broth.

PMID- 24928857
TI  - PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks
      through an allosteric regulatory mechanism shared with PARP-1.
AB  - PARP-1, PARP-2 and PARP-3 are DNA-dependent PARPs that localize to DNA damage,
      synthesize poly(ADP-ribose) (PAR) covalently attached to target proteins
      including themselves, and thereby recruit repair factors to DNA breaks to
      increase repair efficiency. PARP-1, PARP-2 and PARP-3 have in common two C
      terminal domains-Trp-Gly-Arg (WGR) and catalytic (CAT). In contrast, the N
      terminal region (NTR) of PARP-1 is over 500 residues and includes four regulatory
      domains, whereas PARP-2 and PARP-3 have smaller NTRs (70 and 40 residues,
      respectively) of unknown structural composition and function. Here, we show that
      PARP-2 and PARP-3 are preferentially activated by DNA breaks harboring a 5'
      phosphate (5'P), suggesting selective activation in response to specific DNA
      repair intermediates, in particular structures that are competent for DNA
      ligation. In contrast to PARP-1, the NTRs of PARP-2 and PARP-3 are not strictly
      required for DNA binding or for DNA-dependent activation. Rather, the WGR domain
      is the central regulatory domain of PARP-2 and PARP-3. Finally, PARP-1, PARP-2
      and PARP-3 share an allosteric regulatory mechanism of DNA-dependent catalytic
      activation through a local destabilization of the CAT. Collectively, our study
      provides new insights into the specialization of the DNA-dependent PARPs and
      their specific roles in DNA repair pathways. 

PMID- 24928858
TI  - Critical role for p53-serine 15 phosphorylation in stimulating transactivation at
      p53-responsive promoters.
AB  - The p53 tumour suppressor is induced by various stress stimuli and coordinates an
      adaptive gene expression programme leading to growth arrest or cell death. Some
      stimuli, such as DNA damage, lead to rapid and substantial multisite
      phosphorylation of p53, nucleated initially through phosphorylation of serine 15.
      Other stimuli, such as hyper-proliferation, do not stimulate p53-phosphorylation,
      raising questions regarding the physiological role for phosphorylation. Here, we
      show that a basal level of Ser15 phosphorylation occurs in both unstimulated
      cells and cells stimulated pharmacologically to induce p53. p53 in which Ser15 is
      substituted by alanine (S15A) fails to mediate p53-dependent transcription or
      growth arrest but can be rescued by substitution with aspartate (S15D: a phospho
      mimic). Chromatin immunoprecipitation (ChIP) analyses show that, while wt- and
      S15A-p53 are detectable on the CDKN1A (p21) promoter (as a representative p53
      responsive promoter), S15A-p53 does not stimulate histone acetylation (a measure
      of chromatin relaxation), nor is its recruitment stimulated, in response to a DNA
      damage or pharmacological stimulus. These data demonstrate that Ser15
      phosphorylation is required for p53 function in the physiological context of p53
      responsive promoters and suggest a key and possibly universal role even for low
      levels of this modification in promoting p53-transcription function. 

PMID- 24928859
TI  - Magnetic resonance direct thrombus imaging differentiates acute recurrent
      ipsilateral deep vein thrombosis from residual thrombosis.
AB  - Accurate diagnostic assessment of suspected ipsilateral recurrent deep vein
      thrombosis (DVT) is a major clinical challenge because differentiating between
      acute recurrent thrombosis and residual thrombosis is difficult with compression
      ultrasonography (CUS). We evaluated noninvasive magnetic resonance direct
      thrombus imaging (MRDTI) in a prospective study of 39 patients with symptomatic
      recurrent ipsilateral DVT (incompressibility of a different proximal venous
      segment than at the prior DVT) and 42 asymptomatic patients with at least 6-month
      old chronic residual thrombi and normal D-dimer levels. All patients were
      subjected to MRDTI. MRDTI images were judged by 2 independent radiologists
      blinded for the presence of acute DVT and a third in case of disagreement. The
      sensitivity, specificity, and interobserver reliability of MRDTI were determined.
      MRDTI demonstrated acute recurrent ipsilateral DVT in 37 of 39 patients and was
      normal in all 42 patients without symptomatic recurrent disease for a sensitivity
      of 95% (95% CI, 83% to 99%) and a specificity of 100% (95% CI, 92% to 100%).
      Interobserver agreement was excellent (kappa = 0.98). MRDTI images were adequate
      for interpretation in 95% of the cases. MRDTI is a sensitive and reproducible
      method for distinguishing acute ipsilateral recurrent DVT from 6-month-old
      chronic residual thrombi in the leg veins. 

PMID- 24928860
TI  - Bone marrow stromal cell-derived exosomes as communicators in drug resistance in
      multiple myeloma cells.
AB  - The interplay between bone marrow stromal cells (BMSCs) and multiple myeloma (MM)
      cells performs a crucial role in MM pathogenesis by secreting growth factors,
      cytokines, and extracellular vesicles. Exosomes are membranous vesicles 40 to 100
      nm in diameter constitutively released by almost all cell types, and they mediate
      local cell-to-cell communication by transferring mRNAs, miRNAs, and proteins.
      Although BMSC-induced growth and drug resistance of MM cells has been studied,
      the role of BMSC-derived exosomes in this action remains unclear. Here we
      investigate the effect of BMSC-derived exosomes on the viability, proliferation,
      survival, migration, and drug resistance of MM cells, using the murine 5T33MM
      model and human MM samples. BMSCs and MM cells could mutually exchange exosomes
      carrying certain cytokines. Both naive and 5T33 BMSC-derived exosomes increased
      MM cell growth and induced drug resistance to bortezomib. BMSC-derived exosomes
      also influenced the activation of several survival relevant pathways, including c
      Jun N-terminal kinase, p38, p53, and Akt. Exosomes obtained from normal donor and
      MM patient BMSCs also induced survival and drug resistance of human MM cells.
      Taken together, our results demonstrate the involvement of exosome-mediated
      communication in BMSC-induced proliferation, migration, survival, and drug
      resistance of MM cells. 

PMID- 24928862
TI  - Ciz1 is a novel predictor of survival in human colon cancer.
AB  - Cip1-interacting zinc-finger protein1 (Ciz1) is a nuclear matrix protein
      associated DNA replication factor which has been implicated in breast and lung
      cancer progression. However, the clinical significance of Ciz1 expression in
      colon cancer has not been determined. This study aimed to examine Ciz1 expression
      pattern and its potential as a biomarker of prognosis in colon cancer. Using
      quantitative PCR, tissue microarray (TMA), and ELISA, we evaluated Ciz1 mRNA and
      protein levels in tumor tissues from patients with colon cancer and in paired
      adjacent normal tissues. Ciz1 mRNA expression was significantly upregulated in 22
      of 39 paired samples (P < 0.001). Immunohistochemistry on TMA-containing samples
      from 203 colon cancer patients indicated that Ciz1 protein expression was
      significantly higher in tumor tissues than in adjacent normal tissues (Stuart
      Maxwell test, P < 0.001). Elevated expression of Ciz1 protein was significantly
      correlated with T stage (P < 0.001), N stage (P = 0.005), M stage (P = 0.021),
      and AJCC stage (P = 0.002). Multivariate Cox proportion hazard model analysis
      revealed that Ciz1 expression is an independent prognostic factor for overall
      time (OS; hazard ratio (HR): 1.76; 95% confidence interval (CI): 1.04-2.98; P =
      0.034) and disease-free survival (DFS; HR: 2.02; 95% CI: 1.14-3.58; P = 0.017) of
      patients with colon cancer after colectomy. Our data suggested that Ciz1 may be
      involved in colon cancer progression and could serve as a novel predictor of
      survival for colon cancer patients.

PMID- 24928861
TI  - von Willebrand factor, Jedi knight of the bloodstream.
AB  - When blood vessels are cut, the forces in the bloodstream increase and change
      character. The dark side of these forces causes hemorrhage and death. However,
      von Willebrand factor (VWF), with help from our circulatory system and platelets,
      harnesses the same forces to form a hemostatic plug. Force and VWF function are
      so closely intertwined that, like members of the Jedi Order in the movie Star
      Wars who learn to use "the Force" to do good, VWF may be considered the Jedi
      knight of the bloodstream. The long length of VWF enables responsiveness to flow.
      The shape of VWF is predicted to alter from irregularly coiled to extended thread
      like in the transition from shear to elongational flow at sites of hemostasis and
      thrombosis. Elongational force propagated through the length of VWF in its thread
      like shape exposes its monomers for multimeric binding to platelets and
      subendothelium and likely also increases affinity of the A1 domain for platelets.
      Specialized domains concatenate and compact VWF during biosynthesis. A2 domain
      unfolding by hydrodynamic force enables postsecretion regulation of VWF length.
      Mutations in VWF in von Willebrand disease contribute to and are illuminated by
      VWF biology. I attempt to integrate classic studies on the physiology of
      hemostatic plug formation into modern molecular understanding, and point out what
      remains to be learned. 

PMID- 24928863
TI  - Effects of magnesium deficiency--more than skin deep.
AB  - Dead Sea and magnesium salt therapy are two of the oldest forms of treatment for
      skin disease and several other disorders, supported by a body of largely
      anecdotal evidence. In this paper we review possible pathways for penetration of
      magnesium ions through the epidermis to reach the circulation, in turn
      replenishing cellular magnesium levels. We also discuss mechanisms for
      intercellular movement of magnesium ions and possible mechanisms for the
      interaction between magnesium ions and inflammatory mediators. Upon addition of
      magnesium ions in vitro, the expression of inflammatory mediators such as tumour
      necrosis factor alpha (TNFalpha) and nuclear factor kappabeta (NFkappabeta) is
      down regulated. Dysregulation of these and other inflammatory mediators has been
      linked to several inflammatory disorders, including asthma, arthritis,
      atherosclerosis and neuroinflammation. 

PMID- 24928864
TI  - New concepts concerning prostate cancer screening.
AB  - Prostate Cancer (CaP) is rapidly becoming a worldwide health issue. While CaP
      mortality has decreased in recent years, coincident with the widespread use of
      Prostate-Specific Antigen (PSA) screening, it remains the most common solid tumor
      in men and is the second leading cause of cancer death in the United States. The
      frequency of CaP is growing not only in western cultures, but also its incidence
      is dramatically increasing in eastern nations. Recently, examination of data from
      long-term trials and follow up has cast a shadow on the effectiveness of
      employing PSA as a primary screening tool for CaP. In this review, we not only
      summarize opinions from this examination and synthesize recommendations from
      several groups that suggest strategies for utilizing PSA as a tool, but also call
      for research into biomarkers for CaP diagnosis and disease progression. We also
      describe our recent work that identified a smooth muscle contractile protein in
      prostate epithelia, namely smooth muscle gamma actin, and indicate the potential
      for this molecule as a new unique footprint and as a CaP marker.

PMID- 24928865
TI  - Polysaccharides from Laminaria japonica show hypoglycemic and hypolipidemic
      activities in mice with experimentally induced diabetes.
AB  - Diabetes mellitus (DM) is a chronic metabolic disorder of the endocrine system.
      The rapid increase in the incidence of DM is a serious public health concern
      worldwide. The treatment of DM and its complications mainly involves the use of
      chemically or biochemically synthesized drugs, but these drugs also have adverse
      side effects. Therefore, there is an urgent need to search for drugs from natural
      sources that would cause fewer side effects. This study aimed to determine
      whether polysaccharides from Laminaria japonica (LJP) exert hypoglycemic and
      hypolipidemic effects in mice with alloxan-induced diabetes. To this end,
      diabetes was induced by alloxan injection (200 mg/kg body weight [bw],
      intraperitoneal [ip]). After induction of diabetes, diabetic mice were randomly
      divided into five groups: diabetic control (DC) group, glibenclamide-treated (DG)
      group, low-dose LJP-treated (DLL) group, moderate-dose LJP-treated (DML) group,
      and high-dose LJP-treated (DHL) group, with normal mice used as the control group
      (NC group). After treatment for 28 days, body weight, fasting blood glucose
      (FBG), serum insulin, total cholesterol (TC), triglyceride (TG), high-density
      lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C)
      levels were measured. The results revealed that LJP administration prevented body
      weight loss, decreased FBG levels, and increased serum insulin levels in diabetic
      mice. Furthermore, it decreased TC, TG, and LDL-C levels, and increased HDL-C
      levels in these mice. Thus, the results indicate that LJP possesses hypoglycemic
      and hypolipidemic activities and polysaccharides from LJP may hold promise for
      the development of a drug of natural origin for the treatment of DM. 

PMID- 24928866
TI  - Steroids inhibit vascular endothelial growth factor expression via TLR4/Akt/NF
      kappaB pathway in chronic rhinosinusitis with nasal polyp.
AB  - Vascular endothelial growth factor (VEGF) is elevated in chronic rhinosinusitis
      with nasal polyps. Steroids have anti-inflammatory properties and are ideal
      candidates for treating chronic inflammatory airways. The aims of this study were
      to identify the inhibitory effects and mechanisms of steroids on
      lipopolysaccharide (LPS)-induced VEGF expression in nasal polyps. Nasal polyp
      derived fibroblasts (NPDFs) were stimulated with LPS alone or with both LPS and
      steroids were used to determine the expression levels of toll-like receptor (TLR)
      4, myeloid differentiation primary response gene 88 (MyD88), and VEGF by using
      reverse transcription-polymerase chain reaction (RT-PCR). VEGF protein level was
      analyzed by immunocytochemical staining and enzyme-linked immunosorbent assay
      (ELISA). Small interfering RNA (siRNA) for TLR4 was transfected to down-regulate
      TLR4 expression. Activation of Akt and nuclear factor kappaB (NF-kappaB) pathway
      on VEGF expression was determined by Western blot analysis, immunocytochemical
      staining, and ELISA. Nasal polyp organ cultures were stimulated with LPS alone or
      in conjunction with steroids or LPS-RS (TLR4 inhibitor) and accessed the
      expression of VEGF. Steroids decreased the expressions of TLR4, MyD88, and VEGF
      mRNA and VEGF protein in LPS-stimulated NPDFs. Steroids inhibited LPS-induced
      VEGF expression levels in dose-dependent manner. The suppression of TLR4
      transcription by siRNA treatment reduced LPS-induced expression of both TLR4 and
      VEGF in NPDFs. Furthermore, steroids inhibited the production of VEGF by blocking
      Akt and NF-kappaB activation and preventing with NF-kappaB translocation. Also,
      steroid and TLR4 inhibitor decreased VEGF expression in nasal polyp organ
      cultures. These results indicate that steroids inhibit LPS-induced VEGF
      expression through the TLR4/Akt/NF-kappaB signaling pathway in chronic
      rhinosinusitis with nasal polyp.

PMID- 24928867
TI  - Child and adolescent mental health referrals jump as cases get more extreme and
      complex, MPs hear.

PMID- 24928868
TI  - WHO FCTC article 5.3: promise but little progress.

PMID- 24928869
TI  - Uptake and metabolism of N-acetylglucosamine and glucosamine by Streptococcus
      mutans.
AB  - Glucosamine and N-acetylglucosamine are among the most abundant sugars on the
      planet, and their introduction into the oral cavity via the diet and host
      secretions, and through bacterial biosynthesis, provides oral biofilm bacteria
      with a source of carbon, nitrogen, and energy. In this study, we demonstrated
      that the dental caries pathogen Streptococcus mutans possesses an inducible
      system for the metabolism of N-acetylglucosamine and glucosamine. These amino
      sugars are transported by the phosphoenolpyruvate:sugar phosphotransferase system
      (PTS), with the glucose/mannose enzyme II permease encoded by manLMN playing a
      dominant role. Additionally, a previously uncharacterized gene product encoded
      downstream of the manLMN operon, ManO, was shown to influence the efficiency of
      uptake and growth on N-acetylglucosamine and, to a lesser extent, glucosamine. A
      transcriptional regulator, designated NagR, was able to bind the promoter regions
      in vitro, and repress the expression in vivo, of the nagA and nagB genes,
      encoding N-acetylglucosamine-6-phosphate deacetylase and glucosamine-6-phosphate
      deaminase, respectively. The binding activity of NagR could be inhibited by
      glucosamine-6-phosphate in vitro. Importantly, in contrast to the case with
      certain other Firmicutes, the gene for de novo synthesis of glucosamine-6
      phosphate in S. mutans, glmS, was also shown to be regulated by NagR, and NagR
      could bind the glmS promoter region in vitro. Finally, metabolism of these amino
      sugars by S. mutans resulted in the production of significant quantities of
      ammonia, which can neutralize cytoplasmic pH and increase acid tolerance, thus
      contributing to enhanced persistence and pathogenic potential. 

PMID- 24928870
TI  - Metaproteomic identification of diazotrophic methanotrophs and their localization
      in root tissues of field-grown rice plants.
AB  - In a previous study by our group, CH4 oxidation and N2 fixation were
      simultaneously activated in the roots of wild-type rice plants in a paddy field
      with no N input; both processes are likely controlled by a rice gene for
      microbial symbiosis. The present study examined which microorganisms in rice
      roots were responsible for CH4 oxidation and N2 fixation under the field
      conditions. Metaproteomic analysis of root-associated bacteria from field-grown
      rice (Oryza sativa Nipponbare) revealed that nitrogenase complex-containing
      nitrogenase reductase (NifH) and the alpha subunit (NifD) and beta subunit (NifK)
      of dinitrogenase were mainly derived from type II methanotrophic bacteria of the
      family Methylocystaceae, including Methylosinus spp. Minor nitrogenase proteins
      such as Methylocella, Bradyrhizobium, Rhodopseudomonas, and Anaeromyxobacter were
      also detected. Methane monooxygenase proteins (PmoCBA and MmoXYZCBG) were
      detected in the same bacterial group of the Methylocystaceae. Because these
      results indicated that Methylocystaceae members mediate both CH4 oxidation and N2
      fixation, we examined their localization in rice tissues by using catalyzed
      reporter deposition-fluorescence in situ hybridization (CARD-FISH). The
      methanotrophs were localized around the epidermal cells and vascular cylinder in
      the root tissues of the field-grown rice plants. Our metaproteomics and CARD-FISH
      results suggest that CH4 oxidation and N2 fixation are performed mainly by type
      II methanotrophs of the Methylocystaceae, including Methylosinus spp., inhabiting
      the vascular bundles and epidermal cells of rice roots. 

PMID- 24928871
TI  - Following pathogen development and gene expression in a food ecosystem: the case
      of a Staphylococcus aureus isolate in cheese.
AB  - Human intoxication or infection due to bacterial food contamination constitutes
      an economic challenge and a public health problem. Information on the in situ
      distribution and expression of pathogens responsible for this risk is to date
      lacking, largely because of technical bottlenecks in detecting signals from
      minority bacterial populations within a complex microbial and physicochemical
      ecosystem. We simulated the contamination of a real high-risk cheese with a
      natural food isolate of Staphylococcus aureus, an enterotoxin-producing pathogen
      responsible for food poisoning. To overcome the problem of a detection limit in a
      solid matrix, we chose to work with a fluorescent reporter (superfolder green
      fluorescent protein) that would allow spatiotemporal monitoring of S. aureus
      populations and targeted gene expression. The combination of complementary
      techniques revealed that S. aureus localizes preferentially on the cheese surface
      during ripening. Immunochemistry and confocal laser scanning microscopy enabled
      us to visualize, in a single image, dairy bacteria and pathogen populations,
      virulence gene expression, and the toxin produced. This procedure is readily
      applicable to other genes of interest, other bacteria, and different types of
      food matrices. 

PMID- 24928872
TI  - Binding site concentration explains the differential susceptibility of Chilo
      suppressalis and Sesamia inferens to Cry1A-producing rice.
AB  - Chilo suppressalis and Sesamia inferens are two important lepidopteran rice pests
      that occur concurrently during outbreaks in paddy fields in the main rice-growing
      areas of China. Previous and current field tests demonstrate that the transgenic
      rice line Huahui 1 (HH1) producing a Cry1Ab-Cry1Ac hybrid toxin from the
      bacterium Bacillus thuringiensis reduces egg and larval densities of C.
      suppressalis but not of S. inferens. This differential susceptibility to HH1 rice
      correlates with the reduced susceptibility to Cry1Ab and Cry1Ac toxins in S.
      inferens larvae compared to C. suppressalis larvae. The goal of this study was to
      identify the mechanism responsible for this differential susceptibility. In
      saturation binding assays, both Cry1Ab and Cry1Ac toxins bound with high affinity
      and in a saturable manner to midgut brush border membrane vesicles (BBMV) from C.
      suppressalis and S. inferens larvae. While binding affinities were similar, a
      dramatically lower concentration of Cry1A toxin binding sites was detected for S.
      inferens BBMV than for C. suppressalis BBMV. In contrast, no significant
      differences between species were detected for Cry1Ca toxin binding to BBMV.
      Ligand blotting detected BBMV proteins binding Cry1Ac or Cry1Ca toxins, some of
      them unique to C. suppressalis or S. inferens. These data support that reduced
      Cry1A binding site concentration is associated with a lower susceptibility to
      Cry1A toxins and HH1 rice in S. inferens larvae than in C. suppressalis larvae.
      Moreover, our data support Cry1Ca as a candidate for pyramiding efforts with
      Cry1A-producing rice to extend the activity range and durability of this
      technology against rice stem borers. 

PMID- 24928873
TI  - Identification of Mn(II)-oxidizing bacteria from a low-pH contaminated former
      uranium mine.
AB  - Biological Mn oxidation is responsible for producing highly reactive and abundant
      Mn oxide phases in the environment that can mitigate metal contamination.
      However, little is known about Mn oxidation in low-pH environments, where metal
      contamination often is a problem as the result of mining activities. We isolated
      two Mn(II)-oxidizing bacteria (MOB) at pH 5.5 (Duganella isolate AB_14 and
      Albidiferax isolate TB-2) and nine strains at pH 7 from a former uranium mining
      site. Isolate TB-2 may contribute to Mn oxidation in the acidic Mn-rich subsoil,
      as a closely related clone represented 16% of the total community. All isolates
      oxidized Mn over a small pH range, and isolates from low-pH samples only oxidized
      Mn below pH 6. Two strains with different pH optima differed in their Fe
      requirements for Mn oxidation, suggesting that Mn oxidation by the strain found
      at neutral pH was linked to Fe oxidation. Isolates tolerated Ni, Cu, and Cd and
      produced Mn oxides with similarities to todorokite and birnessite, with the
      latter being present in subsurface layers where metal enrichment was associated
      with Mn oxides. This demonstrates that MOB can be involved in the formation of
      biogenic Mn oxides in both moderately acidic and neutral pH environments. 

PMID- 24928874
TI  - DegePrime, a program for degenerate primer design for broad-taxonomic-range PCR
      in microbial ecology studies.
AB  - The taxonomic composition of a microbial community can be deduced by analyzing
      its rRNA gene content by, e.g., high-throughput DNA sequencing or DNA chips. Such
      methods typically are based on PCR amplification of rRNA gene sequences using
      broad-taxonomic-range PCR primers. In these analyses, the use of optimal primers
      is crucial for achieving an unbiased representation of community composition.
      Here, we present the computer program DegePrime that, for each position of a
      multiple sequence alignment, finds a degenerate oligomer of as high coverage as
      possible and outputs its coverage among taxonomic divisions. We show that our
      novel heuristic, which we call weighted randomized combination, performs better
      than previously described algorithms for solving the maximum coverage degenerate
      primer design problem. We previously used DegePrime to design a broad-taxonomic
      range primer pair that targets the bacterial V3-V4 region (341F-805R) (D. P.
      Herlemann, M. Labrenz, K. Jurgens, S. Bertilsson, J. J. Waniek, and A. F.
      Andersson, ISME J. 5:1571-1579, 2011, http://dx.doi.org/10.1038/ismej.2011.41),
      and here we use the program to significantly increase the coverage of a primer
      pair (515F-806R) widely used for Illumina-based surveys of bacterial and archaeal
      diversity. By comparison with shotgun metagenomics, we show that the primers give
      an accurate representation of microbial diversity in natural samples. 

PMID- 24928875
TI  - Alternative sigma factors SigF, SigE, and SigG are essential for sporulation in
      Clostridium botulinum ATCC 3502.
AB  - Clostridium botulinum produces heat-resistant endospores that may germinate and
      outgrow into neurotoxic cultures in foods. Sporulation is regulated by the
      transcription factor Spo0A and the alternative sigma factors SigF, SigE, SigG,
      and SigK in most spore formers studied to date. We constructed mutants of sigF,
      sigE, and sigG in C. botulinum ATCC 3502 and used quantitative reverse
      transcriptase PCR and electron microscopy to assess their expression of the
      sporulation pathway on transcriptional and morphological levels. In all three
      mutants the expression of spo0A was disrupted. The sigF and sigE mutants failed
      to induce sigG and sigK beyond exponential-phase levels and halted sporulation
      during asymmetric cell division. In the sigG mutant, peak transcription of sigE
      was delayed and sigK levels remained lower than that in the parent strain. The
      sigG mutant forespore was engulfed by the mother cell and possessed a spore coat
      but no peptidoglycan cortex. The findings suggest that SigF and SigE of C.
      botulinum ATCC 3502 are essential for early sporulation and late-stage induction
      of sigK, whereas SigG is essential for spore cortex formation but not for coat
      formation, as opposed to previous observations in B. subtilis sigG mutants. Our
      findings add to a growing body of evidence that regulation of sporulation in C.
      botulinum ATCC 3502, and among the clostridia, differs from the B. subtilis
      model. 

PMID- 24928876
TI  - Automated design of probes for rRNA-targeted fluorescence in situ hybridization
      reveals the advantages of using dual probes for accurate identification.
AB  - Fluorescence in situ hybridization (FISH) is a common technique for identifying
      cells in their natural environment and is often used to complement next
      generation sequencing approaches as an integral part of the full-cycle rRNA
      approach. A major challenge in FISH is the design of oligonucleotide probes with
      high sensitivity and specificity to their target group. The rapidly expanding
      number of rRNA sequences has increased awareness of the number of potential
      nontargets for every FISH probe, making the design of new FISH probes challenging
      using traditional methods. In this study, we conducted a systematic analysis of
      published probes that revealed that many have insufficient coverage or
      specificity for their intended target group. Therefore, we developed an improved
      thermodynamic model of FISH that can be applied at any taxonomic level, used the
      model to systematically design probes for all recognized genera of bacteria and
      archaea, and identified potential cross-hybridizations for the selected probes.
      This analysis resulted in high-specificity probes for 35.6% of the genera when a
      single probe was used in the absence of competitor probes and for 60.9% when up
      to two competitor probes were used. Requiring the hybridization of two
      independent probes for positive identification further increased specificity. In
      this case, we could design highly specific probe sets for up to 68.5% of the
      genera without the use of competitor probes and 87.7% when up to two competitor
      probes were used. The probes designed in this study, as well as tools for
      designing new probes, are available online (http://DECIPHER.cee.wisc.edu). 

PMID- 24928877
TI  - Novel three-component Rieske non-heme iron oxygenase system catalyzing the N
      dealkylation of chloroacetanilide herbicides in sphingomonads DC-6 and DC-2.
AB  - Sphingomonads DC-6 and DC-2 degrade the chloroacetanilide herbicides alachlor,
      acetochlor, and butachlor via N-dealkylation. In this study, we report a three
      component Rieske non-heme iron oxygenase (RHO) system catalyzing the N
      dealkylation of these herbicides. The oxygenase component gene cndA is located in
      a transposable element that is highly conserved in the two strains. CndA shares
      24 to 42% amino acid sequence identities with the oxygenase components of some
      RHOs that catalyze N- or O-demethylation. Two putative [2Fe-2S] ferredoxin genes
      and one glutathione reductase (GR)-type reductase gene were retrieved from the
      genome of each strain. These genes were not located in the immediate vicinity of
      cndA. The four ferredoxins share 64 to 72% amino acid sequence identities to the
      ferredoxin component of dicamba O-demethylase (DMO), and the two reductases share
      62 to 65% amino acid sequence identities to the reductase component of DMO. cndA,
      the four ferredoxin genes, and the two reductases genes were expressed in
      Escherichia coli, and the recombinant proteins were purified using Ni-affinity
      chromatography. The individual components or the components in pairs displayed no
      activity; the enzyme mixture showed N-dealkylase activities toward alachlor,
      acetochlor, and butachlor only when CndA-His6 was combined with one of the four
      ferredoxins and one of the two reductases, suggesting that the enzyme consists of
      three components, a homo-oligomer oxygenase, a [2Fe-2S] ferredoxin, and a GR-type
      reductase, and CndA has a low specificity for the electron transport component
      (ETC). The N-dealkylase utilizes NADH, but not NADPH, as the electron donor. 

PMID- 24928878
TI  - Ether- and ester-bound iso-diabolic acid and other lipids in members of
      acidobacteria subdivision 4.
AB  - Recently, iso-diabolic acid (13,16-dimethyl octacosanedioic acid) has been
      identified as a major membrane-spanning lipid of subdivisions 1 and 3 of the
      Acidobacteria, a highly diverse phylum within the Bacteria. This finding pointed
      to the Acidobacteria as a potential source for the bacterial glycerol dialkyl
      glycerol tetraethers that occur ubiquitously in peat, soil, lakes, and hot
      springs. Here, we examined the lipid composition of seven phylogenetically
      divergent strains of subdivision 4 of the Acidobacteria, a bacterial group that
      is commonly encountered in soil. Acid hydrolysis of total cell material released
      iso-diabolic acid derivatives in substantial quantities (11 to 48% of all fatty
      acids). In contrast to subdivisions 1 and 3 of the Acidobacteria, 6 out of the 7
      species of subdivision 4 (excepting "Candidatus Chloracidobacterium
      thermophilum") contained iso-diabolic acid ether bound to a glycerol in larger
      fractional abundance than iso-diabolic acid itself. This is in agreement with the
      analysis of intact polar lipids (IPLs) by high-performance liquid chromatography
      mass spectrometry (HPLC-MS), which showed the dominance of mixed ether-ester
      glycerides. iso-Diabolic acid-containing IPLs were not identified, because these
      IPLs are not released with a Bligh-Dyer extraction, as observed before when
      studying lipid compositions of subdivisions 1 and 3 of the Acidobacteria. The
      presence of ether bonds in the membrane lipids does not seem to be an adaptation
      to temperature, because the five mesophilic isolates contained a larger amount of
      ether lipids than the thermophile "Ca. Chloracidobacterium thermophilum."
      Furthermore, experiments with Pyrinomonas methylaliphatogenes did not reveal a
      major influence of growth temperature over the 50 to 69 degrees C range. 

PMID- 24928879
TI  - Sporadic distribution and distinctive variations of cylindrospermopsin genes in
      cyanobacterial strains and environmental samples from Chinese freshwater bodies.
AB  - Increasing reports of cylindrospermopsins (CYNs) in freshwater ecosystems have
      promoted the demand for identifying all of the potential CYN-producing
      cyanobacterial species. The present study explored the phylogenetic distribution
      and evolution of cyr genes in cyanobacterial strains and water samples from
      China. Four Cylindrospermopsis strains and two Raphidiopsis strains were
      confirmed to produce CYNs. Mutant cyrI and cyrK genes were observed in these
      strains. Cloned cyr gene sequences from eight water bodies were clustered with
      cyr genes from Cylindrospermopsis and Raphidiopsis (C/R group) in the
      phylogenetic trees with high similarities (99%). Four cyrI sequence types and
      three cyrJ sequence types were observed to have different sequence insertions and
      repeats. Phylogenetic analysis of the rpoC1 sequences of the C/R group revealed
      four conserved clades, namely, clade I, clade II, clade III, and clade V. High
      sequence similarities (>97%) in each clade and a divergent clade IV were
      observed. Therefore, CYN producers were sporadically distributed in congeneric
      and paraphyletic C/R group species in Chinese freshwater ecosystems. In the
      evolution of cyr genes, intragenomic translocations and intergenomic transfer
      between local Cylindrospermopsis and Raphidiopsis were emphasized and probably
      mediated by transposases. This research confirms the existence of CYN-producing
      Cylindrospermopsis in China and reveals the distinctive variations of cyr genes. 

PMID- 24928880
TI  - Latex clearing protein-an oxygenase cleaving poly(cis-1,4-isoprene) rubber at the
      cis double bonds.
AB  - Gordonia polyisoprenivorans strain VH2, a potent rubber-degrading actinomycete,
      harbors two latex clearing proteins (Lcps), which are known to be essential for
      the microbial degradation of rubber. However, biochemical information on the
      exact role of this protein in the degradation of polyisoprene was lacking. In
      this study, the gene encoding Lcp1VH2 was heterologously expressed in strains of
      Escherichia coli, the corresponding protein was purified, and its role in rubber
      degradation was examined by measurement of oxygen consumption as well as by
      chromatographic and spectroscopic methods. It turned out that active Lcp1VH2 is a
      monomer and is responsible for the oxidative cleavage of poly(cis-1,4-isoprene)
      in synthetic as well as in natural rubber by the addition of oxygen (O2) to the
      cis double bonds. The resulting oligomers possess repetitive isoprene units with
      aldehyde (CHO-CH2-) and ketone (-CH2-CO-CH3) functional groups at the termini.
      Two fractions with average isoprene contents of 18 and 10, respectively, were
      isolated, thus indicating an endocleavage mechanism. The activity of Lcp1VH2 was
      determined by applying a polarographic assay. Alkenes, acyclic terpenes, or other
      rubber-like polymers, such as poly(cis-1,4-butadiene) or poly(trans-1,4
      isoprene), are not oxidatively cleaved by Lcp1VH2. The pH and temperature optima
      of the enzyme are at pH 7 and 30 degrees C, respectively. Furthermore, it was
      demonstrated that active Lcp1VH2 is a Cu(II)-containing oxygenase that exhibits a
      conserved domain of unknown function which cannot be detected in any other
      hitherto-characterized enzyme. The results presented here indicate that this
      domain might represent a new protein family of oxygenases. 

PMID- 24928881
TI  - Daily expression pattern of protein-encoding genes and small noncoding RNAs in
      synechocystis sp. strain PCC 6803.
AB  - Many organisms harbor circadian clocks with periods close to 24 h. These cellular
      clocks allow organisms to anticipate the environmental cycles of day and night by
      synchronizing circadian rhythms with the rising and setting of the sun. These
      rhythms originate from the oscillator components of circadian clocks and control
      global gene expression and various cellular processes. The oscillator of
      photosynthetic cyanobacteria is composed of three proteins, KaiA, KaiB, and KaiC,
      linked to a complex regulatory network. Synechocystis sp. strain PCC 6803
      possesses the standard cyanobacterial kaiABC gene cluster plus multiple kaiB and
      kaiC gene copies and antisense RNAs for almost every kai transcript. However,
      there is no clear evidence of circadian rhythms in Synechocystis sp. PCC 6803
      under various experimental conditions. It is also still unknown if and to what
      extent the multiple kai gene copies and kai antisense RNAs affect circadian
      timing. Moreover, a large number of small noncoding RNAs whose accumulation
      dynamics over time have not yet been monitored are known for Synechocystis sp.
      PCC 6803. Here we performed a 48-h time series transcriptome analysis of
      Synechocystis sp. PCC 6803, taking into account periodic light-dark phases,
      continuous light, and continuous darkness. We found that expression of
      functionally related genes occurred in different phases of day and night.
      Moreover, we found day-peaking and night-peaking transcripts among the small
      RNAs; in particular, the amounts of kai antisense RNAs correlated or
      anticorrelated with those of their respective kai target mRNAs, pointing toward
      the regulatory relevance of these antisense RNAs. Surprisingly, we observed that
      the amounts of 16S and 23S rRNAs in this cyanobacterium fluctuated in light-dark
      periods, showing maximum accumulation in the dark phase. Importantly, the amounts
      of all transcripts, including small noncoding RNAs, did not show any rhythm under
      continuous light or darkness, indicating the absence of circadian rhythms in
      Synechocystis. 

PMID- 24928882
TI  - Does Campylobacter jejuni form biofilms in food-related environments?
AB  - Campylobacter jejuni is one of the most frequent causes of bacterial
      gastrointestinal food-borne infection worldwide. This species is part of the
      normal flora of the gastrointestinal tracts of animals used for food production,
      including poultry, which is regarded as the primary source of human Campylobacter
      infections. The survival and persistence of C. jejuni in food processing
      environments, especially in poultry processing plants, represent significant risk
      factors that contribute to the spread of this pathogen through the food chain.
      Compared to other food-borne pathogens, C. jejuni is more fastidious in its
      growth requirements and is very susceptible to various environmental stressors.
      Biofilm formation is suggested to play a significant role in the survival of C.
      jejuni in the food production and processing environment. The aims of this
      minireview were (i) to examine the evidence that C. jejuni forms biofilms and
      (ii) to establish the extent to which reported and largely laboratory-based
      studies of C. jejuni biofilms provide evidence for biofilm formation by this
      pathogen in food processing environments. Overall existing studies do not provide
      strong evidence for biofilm formation (as usually defined) by most C. jejuni
      strains in food-related environments under the combined conditions of atmosphere,
      temperature, and shear that they are likely to encounter. Simple attachment to
      and survival on surfaces and in existing biofilms of other species are far more
      likely to contribute to C. jejuni survival in food-related environments based on
      our current understanding of this species. 

PMID- 24928883
TI  - Epithelial adhesion mediated by pilin SpaC is required for Lactobacillus
      rhamnosus GG-induced cellular responses.
AB  - Lactobacillus rhamnosus GG is a widely used probiotic, and the strain's salutary
      effects on the intestine have been extensively documented. We previously reported
      that strain GG can modulate inflammatory signaling, as well as epithelial
      migration and proliferation, by activating NADPH oxidase 1-catalyzed generation
      of reactive oxygen species (ROS). However, how strain GG induces these responses
      is unknown. Here, we report that strain GG's probiotic benefits are dependent on
      the bacterial-epithelial interaction mediated by the SpaC pilin subunit. By
      comparing strain GG to an isogenic mutant that lacks SpaC (strain GGOmegaspaC),
      we establish that SpaC is necessary for strain GG to adhere to gut mucosa, that
      SpaC contributes to strain GG-induced epithelial generation of ROS, and that SpaC
      plays a role in strain GG's capacity to stimulate extracellular signal-regulated
      kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in enterocytes. In
      addition, we show that SpaC is required for strain GG-mediated stimulation of
      cell proliferation and protection against radiologically inflicted intestinal
      injury. The identification of a critical surface protein required for strain GG
      to mediate its probiotic influence advances our understanding of the molecular
      basis for the symbiotic relationship between some commensal bacteria of the gut
      lumen and enterocytes. Further insights into this relationship are critical for
      the development of novel approaches to treat intestinal diseases. 

PMID- 24928885
TI  - Modeling bacterial population growth from stochastic single-cell dynamics.
AB  - A few bacterial cells may be sufficient to produce a food-borne illness outbreak,
      provided that they are capable of adapting and proliferating on a food matrix.
      This is why any quantitative health risk assessment policy must incorporate
      methods to accurately predict the growth of bacterial populations from a small
      number of pathogens. In this aim, mathematical models have become a powerful
      tool. Unfortunately, at low cell concentrations, standard deterministic models
      fail to predict the fate of the population, essentially because the heterogeneity
      between individuals becomes relevant. In this work, a stochastic differential
      equation (SDE) model is proposed to describe variability within single-cell
      growth and division and to simulate population growth from a given initial number
      of individuals. We provide evidence of the model ability to explain the observed
      distributions of times to division, including the lag time produced by the
      adaptation to the environment, by comparing model predictions with experiments
      from the literature for Escherichia coli, Listeria innocua, and Salmonella
      enterica. The model is shown to accurately predict experimental growth population
      dynamics for both small and large microbial populations. The use of stochastic
      models for the estimation of parameters to successfully fit experimental data is
      a particularly challenging problem. For instance, if Monte Carlo methods are
      employed to model the required distributions of times to division, the parameter
      estimation problem can become numerically intractable. We overcame this
      limitation by converting the stochastic description to a partial differential
      equation (backward Kolmogorov) instead, which relates to the distribution of
      division times. Contrary to previous stochastic formulations based on random
      parameters, the present model is capable of explaining the variability observed
      in populations that result from the growth of a small number of initial cells as
      well as the lack of it compared to populations initiated by a larger number of
      individuals, where the random effects become negligible. 

PMID- 24928884
TI  - Insect gut bacterial diversity determined by environmental habitat, diet,
      developmental stage, and phylogeny of host.
AB  - Insects are the most abundant animals on Earth, and the microbiota within their
      guts play important roles by engaging in beneficial and pathological interactions
      with these hosts. In this study, we comprehensively characterized insect
      associated gut bacteria of 305 individuals belonging to 218 species in 21
      taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374
      sequence reads were obtained, identifying 9,301 bacterial operational taxonomic
      units (OTUs) at the 3% distance level from all samples, with an average of 84.3
      (+/- 97.7) OTUs per sample. The insect gut microbiota were dominated by
      Proteobacteria (62.1% of the total reads, including 14.1% Wolbachia sequences)
      and Firmicutes (20.7%). Significant differences were found in the relative
      abundances of anaerobes in insects and were classified according to the criteria
      of host environmental habitat, diet, developmental stage, and phylogeny. Gut
      bacterial diversity was significantly higher in omnivorous insects than in
      stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning
      investigation of the gut microbiota provides insights into the relationships
      between insects and their gut bacterial communities.

PMID- 24928887
TI  - Consultant who accused himself of sexual misconduct is struck off.

PMID- 24928886
TI  - Microbial successions are associated with changes in chemical profiles of a model
      refrigerated fresh pork sausage during an 80-day shelf life study.
AB  - Fresh pork sausage is produced without a microbial kill step and therefore
      chilled or frozen to control microbial growth. In this report, the microbiota in
      a chilled fresh pork sausage model produced with or without an antimicrobial
      combination of sodium lactate and sodium diacetate was studied using a
      combination of traditional microbiological methods and deep pyrosequencing of 16S
      rRNA gene amplicons. In the untreated system, microbial populations rose from
      10(2) to 10(6) CFU/g within 15 days of storage at 4 degrees C, peaking at nearly
      10(8) CFU/g by day 30. Pyrosequencing revealed a complex community at day 0, with
      taxa belonging to the Bacilli, Gammaproteobacteria, Betaproteobacteria,
      Actinobacteria, Bacteroidetes, and Clostridia. During storage at 4 degrees C, the
      untreated system displayed a complex succession, with species of Weissella and
      Leuconostoc that dominate the product at day 0 being displaced by species of
      Pseudomonas (P. lini and P. psychrophila) within 15 days. By day 30, a second
      wave of taxa (Lactobacillus graminis, Carnobacterium divergens, Buttiauxella
      brennerae, Yersinia mollaretti, and a taxon of Serratia) dominated the
      population, and this succession coincided with significant chemical changes in
      the matrix. Treatment with lactate-diacetate altered the dynamics dramatically,
      yielding a monophasic growth curve of a single species of Lactobacillus (L.
      graminis), followed by a uniform selective die-off of the majority of species in
      the population. Of the six species of Lactobacillus that were routinely detected,
      L. graminis became the dominant member in all samples, and its origins were
      traced to the spice blend used in the formulation. 

PMID- 24928889
TI  - Extending an in vitro panel for estrogenicity testing: the added value of
      bioassays for measuring antiandrogenic activities and effects on steroidogenesis.
AB  - In the present study, a previously established integrated testing strategy (ITS)
      for in vitro estrogenicity testing was extended with additional in vitro assays
      in order to broaden its sensitivity to different modes of action resulting in
      apparent estrogenicity, i.e., other than estrogen receptor (ER) binding. To this
      end, an extra set of 10 estrogenic compounds with modes of action in part
      different from ER binding, were tested in the previously defined ITS, consisting
      of a yeast estrogen reporter gene assay, an U2OS ERalpha CALUX reporter gene
      assay and a cell-free coregulator binding assay. Two androgen reporter gene
      assays and the enhanced H295R steroidogenesis assay were added to that previous
      defined ITS. These assays had added value, as several estrogenic model compounds
      also elicited clear and potent antiandrogenic properties and in addition also
      showed effects on steroidogenesis that might potentiate their apparent estrogenic
      effects in vivo. Adding these assays, examining mechanisms of action for
      estrogenicity apart from ERalpha binding, gives a more complete and comprehensive
      assessment of the ability of test compounds to interfere with endocrine
      signaling. It was concluded that the extended ITS will go beyond in vivo
      estrogenicity testing by the uterotrophic assay, thereby contributing to the 3R
      principles. 

PMID- 24928890
TI  - Sparking connections: toward better linkages between research and human health
      policy-an example with multiwalled carbon nanotubes.
AB  - Risk assessment and subsequent risk management of environmental contaminants can
      benefit from early collaboration among researchers, risk assessors, and risk
      managers. The benefits of collaboration in research planning are particularly
      evident in light of (1) increasing calls to expand upon the risk assessment
      paradigm to include a greater focus on problem formulation and consideration of
      potential tradeoffs between risk management options, and (2) decreasing research
      budgets. Strategically connecting research planning to future decision making may
      be most critical in areas of emerging science for which data are often
      insufficient to clearly direct targeted research to support future risk
      assessment and management efforts. This article illustrates an application of the
      comprehensive environmental assessment approach to inform research planning for
      future risk assessment and management of one emerging material, multiwalled
      carbon nanotubes (MWCNTs). High-priority research areas identified for MWCNTs in
      flame-retardant coatings applied to upholstery textiles included the following:
      release across the product life cycle; environmental transport, transformation
      and fate in air, wastewater and sediment; exposure in human occupational and
      consumer groups; kinetics in the human body; impacts on human health and aquatic
      populations; and impacts on economic, social, and environmental resources. This
      article focuses on specific research questions related to human health and how
      these may connect to future risk assessments and risk management efforts. Such
      connections will support more effective collaborations across the scientific
      community and may inform the prioritization of research funding opportunities for
      emerging materials like MWCNTs. 

PMID- 24928891
TI  - In silico identification and pharmacological evaluation of novel endocrine
      disrupting chemicals that act via the ligand-binding domain of the estrogen
      receptor alpha.
AB  - Endocrine disrupting chemicals (EDCs) pose a significant threat to human health,
      society, and the environment. Many EDCs elicit their toxic effects through
      nuclear hormone receptors, like the estrogen receptor alpha (ERalpha). In silico
      models can be used to prioritize chemicals for toxicological evaluation to reduce
      the amount of costly pharmacological testing and enable early alerts for newly
      designed compounds. However, many of the current computational models are overly
      dependent on the chemistry of known modulators and perform poorly for novel
      chemical scaffolds. Herein we describe the development of computational, three
      dimensional multi-conformational pocket-field docking, and chemical-field docking
      models for the identification of novel EDCs that act via the ligand-binding
      domain of ERalpha. These models were highly accurate in the retrospective task of
      distinguishing known high-affinity ERalpha modulators from inactive or decoy
      molecules, with minimal training. To illustrate the utility of the models in
      prospective in silico compound screening, we screened a database of over 6000
      environmental chemicals and evaluated the 24 top-ranked hits in an ERalpha
      transcriptional activation assay and a differential scanning fluorimetry-based
      ERalpha binding assay. Promisingly, six chemicals displayed ERalpha agonist
      activity (32nM-3.98MUM) and two chemicals had moderately stabilizing effects on
      ERalpha. Two newly identified active compounds were chemically related beta
      adrenergic receptor (betaAR) agonists, dobutamine, and ractopamine (a feed
      additive that promotes leanness in cattle and poultry), which are the first
      betaAR agonists identified as activators of ERalpha-mediated gene transcription.
      This approach can be applied to other receptors implicated in endocrine
      disruption. 

PMID- 24928892
TI  - In utero exposure to TCDD alters Wnt signaling during mouse prostate development:
      linking ventral prostate agenesis to downregulated beta-catenin signaling.
AB  - In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes ventral
      prostate agenesis in C57BL/6J mice by preventing ventral prostatic budding in the
      embryonic urogenital sinus (UGS). TCDD (5 MUg/kg, po) administered to pregnant
      dams on embryonic day 15.5 (E15.5) activates the aryl hydrocarbon receptor in the
      UGS mesenchyme, disrupting the mesenchymally derived paracrine signaling that
      instructs epithelial prostatic budding. How TCDD alters the mesenchymal milieu is
      not well understood. We previously showed that TCDD disrupts some aspects of Wnt
      signaling in UGSs grown in vitro. Here we provide the first comprehensive, in
      vivo characterization of Wnt signaling in male E16.5 UGSs during normal
      development, and after in utero TCDD exposure. Vehicle- and TCDD-exposed UGSs
      were probed by in situ hybridization to assess relative abundance and
      localization of RNA from 46 genes that regulate Wnt signaling. TCDD altered the
      staining pattern of five genes, increasing staining for Wnt10a and Wnt16 and
      decreasing staining for Ror2, Rspo2, and Wif1. We also used immunohistochemistry
      to show, for the first time, activation of beta-catenin (CTNNB1) signaling in
      ventral basal epithelium of control UGSs at E16.5. This onset of CTNNB1 signaling
      occurred immediately prior to the initiation of ventral prostatic budding and is
      characterized by a pronounced increase in CTNNB1 nuclear localization and
      subsequent expression of the CTNNB1 signaling target gene, Lef1. In utero TCDD
      exposure prevented the onset of CTNNB1 signaling and LEF1 expression in the
      ventral basal epithelium, thereby elucidating a likely mechanism by which TCDD
      contributes to failed prostatic budding in the ventral UGS. 

PMID- 24928893
TI  - Progress in assessing air pollutant risks from in vitro exposures: matching ozone
      dose and effect in human airway cells.
AB  - In vitro exposures to air pollutants could, in theory, facilitate a rapid and
      detailed assessment of molecular mechanisms of toxicity. However, it is difficult
      to ensure that the dose of a gaseous pollutant to cells in tissue culture is
      similar to that of the same cells during in vivo exposure of a living person. The
      goal of the present study was to compare the dose and effect of O3 in airway
      cells of humans exposed in vivo to that of human cells exposed in vitro. Ten
      subjects breathed labeled O3 ((18)O3, 0.3 ppm, 2 h) while exercising
      intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1
      h post exposure for in vivo data whereas in vitro data were obtained from primary
      cultures of human bronchial epithelial cells exposed to 0.25-1.0 ppm (18)O3 for 2
      h. The O3 dose to the cells was defined as the level of (18)O incorporation and
      the O3 effect as the fold increase in expression of inflammatory marker genes (IL
      8 and COX-2). Dose and effect in cells removed from in vivo exposed subjects were
      lower than in cells exposed to the same (18)O3 concentration in vitro suggesting
      upper airway O3 scrubbing in vivo. Cells collected by lavage as well as previous
      studies in monkeys show that cells deeper in the lung receive a higher O3 dose
      than cells in the bronchus. We conclude that the methods used herein show promise
      for replicating and comparing the in vivo dose and effect of O3 in an in vitro
      system. 

PMID- 24928895
TI  - Cortactin-binding protein 2 increases microtubule stability and regulates
      dendritic arborization.
AB  - Neurons are characterized by subcellular compartments, such as axons, dendrites
      and synapses, that have highly specialized morphologies and biochemical
      specificities. Cortactin-binding protein 2 (CTTNBP2), a neuron-specific F-actin
      regulator, has been shown to play a role in the regulation of dendritic spine
      formation and their maintenance. Here, we show that, in addition to F-actin,
      CTTNBP2 also associates with microtubules before mature dendritic spines form.
      This association of CTTNBP2 and microtubules induced the formation of microtubule
      bundles. Although the middle (Mid) region of CTTNBP2 was sufficient for its
      association with microtubules, for microtubule bundling, the N-terminal region
      containing the coiled-coil motifs (NCC), which mediates the dimerization or
      oligomerization of CTTNBP2, was also required. Our study indicates that CTTNBP2
      proteins form a dimer or oligomer and brings multiple microtubule filaments
      together to form bundles. In cultured hippocampal neurons, knockdown of CTTNBP2
      or expression of the Mid or NCC domain alone reduced the acetylation levels of
      microtubules and impaired dendritic arborization. This study suggests that
      CTTNBP2 influences both the F-actin and microtubule cytoskeletons and regulates
      dendritic spine formation and dendritic arborization. 

PMID- 24928894
TI  - RhoJ interacts with the GIT-PIX complex and regulates focal adhesion disassembly.
AB  - RhoJ is a Rho GTPase expressed in endothelial cells and tumour cells, which
      regulates cell motility, invasion, endothelial tube formation and focal adhesion
      numbers. This study aimed to further delineate the molecular function of RhoJ.
      Using timelapse microscopy RhoJ was found to regulate focal adhesion disassembly;
      small interfering RNA (siRNA)-mediated knockdown of RhoJ increased focal adhesion
      disassembly time, whereas expression of an active mutant (daRhoJ) decreased it.
      Furthermore, daRhoJ co-precipitated with the GIT-PIX complex, a regulator of
      focal adhesion disassembly. An interaction between daRhoJ and GIT1 was confirmed
      using yeast two-hybrid experiments, and this depended on the Spa homology domain
      of GIT1. GIT1, GIT2, beta-PIX (also known as ARHGEF7) and RhoJ all colocalised in
      focal adhesions and depended on each other for their recruitment to focal
      adhesions. Functionally, the GIT-PIX complex regulated endothelial tube
      formation, with knockdown of both GIT1 and GIT2, or beta-PIX phenocopying RhoJ
      knockdown. RhoJ-knockout mice showed reduced tumour growth and diminished tumour
      vessel density, identifying a role for RhoJ in mediating tumour angiogenesis.
      These studies give new insight into the molecular function of RhoJ in regulating
      cell motility and tumour vessel formation.

PMID- 24928897
TI  - sigma1B adaptin regulates adipogenesis by mediating the sorting of sortilin in
      adipose tissue.
AB  - Here, we describe altered sorting of sortilin in adipocytes deficient for the
      sigma1B-containing AP-1 complex, leading to the inhibition of adipogenesis. The
      AP-1 complex mediates protein sorting between the trans-Golgi network and
      endosomes. Vertebrates express three AP1 sigma1 subunit isoforms - sigma1A,
      sigma1B and sigma1C (also known as AP1S1, AP1S2 and AP1S3, respectively). sigma1B
      deficient mice display impaired recycling of synaptic vesicles and lipodystrophy.
      Here, we show that sortilin is overexpressed in adipose tissue from sigma1B(-/-)
      mice, and that its overexpression in wild-type cells is sufficient to suppress
      adipogenesis. sigma1B-specific binding of sortilin requires the sortilin DxxD-x12
      DSxxxL motif. sigma1B deficiency does not lead to a block of sortilin transport
      out of a specific organelle, but the fraction that reaches lysosomes is reduced.
      Sortilin binds to the receptor DLK1, an inhibitor of adipocyte differentiation,
      and the overexpression of sortilin prevents DLK1 downregulation, leading to
      enhanced inhibition of adipogenesis. DLK1 and sortilin expression are not
      increased in the brain tissue of sigma1B(-/-) mice, although this is the tissue
      with the highest expression of sigma1B and sortilin. Thus, adipose-tissue
      specific and sigma1B-dependent routes for the transport of sortilin exist and are
      involved in the regulation of adipogenesis and adipose-tissue mass. 

PMID- 24928896
TI  - A nuclear ubiquitin-proteasome pathway targets the inner nuclear membrane protein
      Asi2 for degradation.
AB  - The nuclear envelope consists of inner and outer nuclear membranes. Whereas the
      outer membrane is an extension of the endoplasmic reticulum, the inner nuclear
      membrane (INM) represents a unique membranous environment containing specific
      proteins. The mechanisms of integral INM protein degradation are unknown. Here,
      we investigated the turnover of Asi2, an integral INM protein in Saccharomyces
      cerevisiae. We report that Asi2 is degraded by the proteasome independently of
      the vacuole and that it exhibited a half-life of ~45 min. Asi2 exhibits enhanced
      stability in mutants lacking the E2 ubiquitin conjugating enzymes Ubc6 or Ubc7,
      or the E3 ubiquitin ligase Doa10. Consistent with these data, Asi2 is post
      translationally modified by poly-ubiquitylation in a Ubc7- and Doa10-dependent
      manner. Importantly Asi2 degradation is significantly reduced in a sts1-2 mutant
      that fails to accumulate proteasomes in the nucleus, indicating that Asi2 is
      degraded in the nucleus. Our results reveal a molecular pathway that affects the
      stability of integral proteins of the inner nuclear membrane and indicate that
      Asi2 is subject to protein quality control in the nucleus. 

PMID- 24928898
TI  - Displacement of p130Cas from focal adhesions links actomyosin contraction to cell
      migration.
AB  - Cell adhesion complexes provide platforms where cell-generated forces are
      transmitted to the extracellular matrix (ECM). Tyrosine phosphorylation of focal
      adhesion proteins is crucial for cells to communicate with the extracellular
      environment. However, the mechanisms that transmit actin cytoskeletal motion to
      the extracellular environment to drive cell migration are poorly understood. We
      find that the movement of p130Cas (Cas, also known as BCAR1), a mechanosensor at
      focal adhesions, correlates with actin retrograde flow and depends upon
      actomyosin contraction and phosphorylation of the Cas substrate domain (CasSD).
      This indicates that CasSD phosphorylation underpins the physical link between Cas
      and the actin cytoskeleton. Fluorescence recovery after photobleaching (FRAP)
      experiments reveal that CasSD phosphorylation, as opposed to the association of
      Cas with Src, facilitates Cas displacement from adhesion complexes in migrating
      cells. Furthermore, the stabilization of Src-Cas binding and inhibition of myosin
      II, both of which sustain CasSD phosphorylation but mitigate Cas displacement
      from adhesion sites, retard cell migration. These results indicate that Cas
      promotes cell migration by linking actomyosin contractions to the adhesion
      complexes through a dynamic interaction with Src as well as through the
      phosphorylation-dependent association with the actin cytoskeleton. 

PMID- 24928899
TI  - Dynamics of the Toxoplasma gondii inner membrane complex.
AB  - Unlike most cells, protozoa in the phylum Apicomplexa divide by a distinctive
      process in which multiple daughters are assembled within the mother (schizogony
      or endodyogeny), using scaffolding known as the inner membrane complex (IMC). The
      IMC underlies the plasma membrane during interphase, but new daughters develop in
      the cytoplasm, as cytoskeletal filaments associate with flattened membrane
      cisternae (alveolae), which elongate rapidly to encapsulate subcellular
      organelles. Newly assembled daughters acquire their plasma membrane as they
      emerge from the mother, leaving behind vestiges of the maternal cell. Although
      the maternal plasma membrane remains intact throughout this process, the maternal
      IMC disappears - is it degraded, or recycled to form the daughter IMC? Exploiting
      fluorescently tagged IMC markers, we have used live-cell imaging, fluorescence
      recovery after photobleaching (FRAP) and mEos2 photoactivation to monitor the
      dynamics of IMC biogenesis and turnover during the replication of Toxoplasma
      gondii tachyzoites. These studies reveal that the formation of the T. gondii IMC
      involves two distinct steps - de novo assembly during daughter IMC elongation
      within the mother cell, followed by recycling of maternal IMC membranes after the
      emergence of daughters from the mother cell. 

PMID- 24928901
TI  - Reconstitution of human rRNA gene transcription in mouse cells by a complete SL1
      complex.
AB  - An important characteristic of the transcription of a ribosomal RNA gene (rDNA)
      mediated by DNA-dependent RNA polymerase (Pol) I is its stringent species
      specificity. SL1/TIF-IB is a key complex for species specificity, but its
      functional complex has not been reconstituted. Here, we established a novel and
      highly sensitive monitoring system for Pol I transcription to reconstitute the
      SL1 activity in which a transcript harboring a reporter gene synthesized by Pol I
      is amplified and converted into translatable mRNA by the influenza virus RNA
      dependent RNA polymerase. Using this monitoring system, we reconstituted Pol I
      transcription from the human rDNA promoter in mouse cells by expressing four
      human TATA-binding protein (TBP)-associated factors (TAFIs) in the SL1 complex.
      The reconstituted SL1 also re-activated human rDNA transcription in mouse A9
      cells carrying an inactive human chromosome 21 that contains the rDNA cluster.
      Chimeric SL1 complexes containing human and mouse TAFIs could be formed, but
      these complexes were inactive for human rDNA transcription. We conclude that four
      human TAFIs are necessary and sufficient to overcome the barrier of species
      specificity for human rDNA transcription in mouse cells. 

PMID- 24928900
TI  - A specific subset of E2 ubiquitin-conjugating enzymes regulate Parkin activation
      and mitophagy differently.
AB  - Loss-of-function mutations in the genes encoding PINK1 and Parkin (also known as
      PARK2) are the most common causes of recessive Parkinson's disease. Both together
      mediate the selective degradation of mitochondrial proteins and whole organelles
      via the proteasome and the autophagy-lysosome pathway (mitophagy). The
      mitochondrial kinase PINK1 activates and recruits the E3 ubiquitin ligase Parkin
      to de-energized mitochondria. However, the cognate E2 co-enzymes of Parkin in
      this ubiquitin-dependent pathway have not been investigated. Here, we discovered
      a total of four E2s that either positively or negatively regulate the activation,
      translocation and enzymatic functions of Parkin during mitochondrial quality
      control. UBE2D family members and UBE2L3 redundantly charged the RING-HECT hybrid
      ligase Parkin with ubiquitin, resulting in its initial activation and
      translocation to mitochondria. UBE2N, however, primarily operated through a
      different mechanism in order to mediate the proper clustering of mitochondria, a
      prerequisite for degradation. Strikingly, in contrast to UBE2D, UBE2L3 and UBE2N,
      depletion of UBE2R1 resulted in enhanced Parkin translocation and clustering upon
      mitochondrial uncoupling. Our study uncovered redundant, cooperative or
      antagonistic functions of distinct E2 enzymes in the regulation of Parkin and
      mitophagy that might suggest a putative role in Parkinson's disease pathogenesis.

PMID- 24928902
TI  - Recruitment of septin cytoskeletal proteins by botulinum toxin A protease
      determines its remarkable stability.
AB  - Proteolytic cleavage of synaptosomal-associated protein 25 by the light chain of
      botulinum neurotoxin type A (LCA) results in a blockade of neurotransmitter
      release that persists for several months in motor neurons. The L428A/L429A
      mutation in LCA is known to significantly shorten both the proteolytic and
      neuroparalytic effects of the neurotoxin in mice. To elucidate the cellular
      mechanism for LCA longevity, we studied the effects of L428A/L429A mutation on
      the interactome, localization and stability of LCA expressed in cultured neuronal
      cells. Mass spectrometry analysis of the LCA interactome showed that the mutation
      prevented the interaction of LCA with septins. The wild-type LCA was concentrated
      in plasma-membrane-associated clusters, colocalizing with septins-2 and septin-7,
      which accumulated in these clusters only in the presence of LCA. The L428A/L429A
      mutation decreased co-clustering of LCA and septins and accelerated proteasomal
      and non-proteasomal degradation of LCA. Similarly, the impairment of septin
      oligomerization by forchlorfenuron or silencing of septin-2 prevented LCA
      interaction and clustering with septins and increased LCA degradation. Therefore,
      the dileucine-mediated LCA-septin co-clustering is crucial for the long-lasting
      stabilization of LCA-related proteolytic and presumably neuroparalytic activity. 

PMID- 24928903
TI  - Myosin VI mediates the movement of NHE3 down the microvillus in intestinal
      epithelial cells.
AB  - The intestinal brush border Na(+)/H(+) exchanger NHE3 is tightly regulated
      through changes in its endocytosis and exocytosis. Myosin VI, a minus-end
      directed actin motor, has been implicated in endocytosis at the inter-microvillar
      cleft and during vesicle remodeling in the terminal web. Here, we asked whether
      myosin VI also regulates NHE3 movement down the microvillus. The basal NHE3
      activity and its surface amount, determined by fluorometry of the ratiometric pH
      indicator BCECF and biotinylation assays, respectively, were increased in myosin
      VI-knockdown (KD) Caco-2/Bbe cells. Carbachol (CCH) and forskolin (FSK)
      stimulated NHE3 endocytosis in control but not in myosin VI KD cells.
      Importantly, immunoelectron microscopy results showed that NHE3 was
      preferentially localized in the basal half of control microvilli but in the
      distal half in myosin VI KD cells. Treatment with dynasore duplicated some
      aspects of myosin VI KD: it increased basal surface NHE3 activity and prevented
      FSK-induced NHE3 endocytosis. However, NHE3 had an intermediate distribution
      along the microvillus (between that in myosin VI KD and untreated cells) in
      dynasore-treated cells. We conclude that myosin VI is required for basal and
      stimulated endocytosis of NHE3 in intestinal cells, and suggest that myosin VI
      also moves NHE3 down the microvillus. 

PMID- 24928904
TI  - Polarizing intestinal epithelial cells electrically through Ror2.
AB  - The apicobasal polarity of enterocytes determines where the brush border membrane
      (apical membrane) will form, but how this apical membrane faces the lumen is not
      well understood. The electrical signal across the epithelium could serve as a
      coordinating cue, orienting and polarizing enterocytes. Here, we show that
      applying a physiological electric field to intestinal epithelial cells, to mimic
      the natural electric field created by the transepithelial potential difference,
      polarized phosphorylation of the actin-binding protein ezrin, increased
      expression of intestinal alkaline phosphatase (ALPI, a differentiation marker)
      and remodeled the actin cytoskeleton selectively on the cathode side. In
      addition, an applied electric field also activated ERK1/2 and LKB1 (also known as
      STK11), key molecules in apical membrane formation. Disruption of the tyrosine
      protein kinase transmembrane receptor Ror2 suppressed activation of ERK1/2 and
      LKB1 significantly, and subsequently inhibited apical membrane formation in
      enterocytes. Our findings indicate that the endogenous electric field created by
      the transepithelial potential difference might act as an essential coordinating
      signal for apical membrane formation at a tissue level, through activation of
      LKB1 mediated by Ror2-ERK signaling. 

PMID- 24928905
TI  - Protein kinase D activity controls endothelial nitric oxide synthesis.
AB  - Vascular endothelial growth factor (VEGF) regulates key functions of the
      endothelium, such as angiogenesis or vessel repair in processes involving
      endothelial nitric oxide synthase (eNOS) activation. One of the effector kinases
      that become activated in endothelial cells upon VEGF treatment is protein kinase
      D (PKD). Here, we show that PKD phosphorylates eNOS, leading to its activation
      and a concomitant increase in NO synthesis. Using mass spectrometry, we show that
      the purified active kinase specifically phosphorylates recombinant eNOS on
      Ser1179. Treatment of endothelial cells with VEGF or phorbol 12,13-dibutyrate
      (PDBu) activates PKD and increases eNOS Ser1179 phosphorylation. In addition,
      pharmacological inhibition of PKD and gene silencing of both PKD1 and PKD2
      abrogate VEGF signaling, resulting in a clear diminished migration of endothelial
      cells in a wound healing assay. Finally, inhibition of PKD in mice results in an
      almost complete disappearance of the VEGF-induced vasodilatation, as monitored
      through determination of the diameter of the carotid artery. Hence, our data
      indicate that PKD is a new regulatory kinase of eNOS in endothelial cells whose
      activity orchestrates mammalian vascular tone.

PMID- 24928907
TI  - The KCl-cotransporter KCC2 linked to epilepsy.

PMID- 24928906
TI  - Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in
      a novel pathway.
AB  - The morphology and polarized growth of cells depend on pathways that control the
      asymmetric distribution of regulatory factors. The evolutionarily conserved Ndr
      kinases play important roles in cell polarity and morphogenesis in yeast and
      invertebrates but it is unclear whether they perform a similar function in
      mammalian cells. Here, we analyze the function of mammalian Ndr1 and Ndr2 (also
      known as STK38 or STK38L, respectively) in the establishment of polarity in
      neurons. We show that they act downstream of the tumor suppressor Rassf5 and
      upstream of the polarity protein Par3 (also known as PARD3). Rassf5 and Ndr1 or
      Ndr2 are required during the polarization of hippocampal neurons to prevent the
      formation of supernumerary axons. Mechanistically, the Ndr kinases act by
      phosphorylating Par3 at Ser383 to inhibit its interaction with dynein, thereby
      polarizing the distribution of Par3 and reinforcing axon specification. Our
      results identify a novel Rassf5-Ndr-Par3 signaling cascade that regulates the
      transport of Par3 during the establishment of neuronal polarity. Their role in
      neuronal polarity suggests that Ndr kinases perform a conserved function as
      regulators of cell polarity. 

PMID- 24928909
TI  - Conformational plasticity of the influenza A virus NS1 protein.
AB  - During infection, the influenza A virus non-structural protein 1 (NS1) interacts
      with a diverse range of viral and cellular factors to antagonize host antiviral
      defences and promote viral replication. Here, I review the structural basis for
      some of these functions and discuss the emerging view that NS1 cannot simply be
      regarded as a 'static' protein with a single structure. Rather, the dynamic
      property of NS1 to adopt various quaternary conformations is critical for its
      multiple activities. Understanding NS1 plasticity, and the mechanisms governing
      this plasticity, will be essential for assessing both fundamental protein
      function and the consequences of strain-dependent polymorphisms in this important
      virulence factor. 

PMID- 24928908
TI  - Genetically encoded impairment of neuronal KCC2 cotransporter function in human
      idiopathic generalized epilepsy.
AB  - The KCC2 cotransporter establishes the low neuronal Cl(-) levels required for
      GABAA and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in
      model organisms results in network hyperexcitability. However, no mutations in
      KCC2 have been documented in human disease. Here, we report two non-synonymous
      functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical
      association with idiopathic generalized epilepsy (IGE). These variants reside in
      conserved residues in the KCC2 cytoplasmic C-terminus, exhibit significantly
      impaired Cl(-)-extrusion capacities resulting in less hyperpolarized Gly
      equilibrium potentials (EG ly), and impair KCC2 stimulatory phosphorylation at
      serine 940, a key regulatory site. These data describe a novel KCC2 variant
      significantly associated with a human disease and suggest genetically encoded
      impairment of KCC2 functional regulation may be a risk factor for the development
      of human IGE. 

PMID- 24928911
TI  - Serum concentrations of afamin are elevated in patients with polycystic ovary
      syndrome.
AB  - Oxidative stress seems to be present in patients with polycystic ovary syndrome
      (PCOS). The aim of this study was to evaluate the correlation between
      characteristics of PCOS and serum concentrations of afamin, a novel binding
      protein for the antioxidant vitamin E. A total of 85 patients with PCOS and 76
      control subjects were investigated in a pilot cross-sectional study design
      between 2009 and 2013 in the University Hospital of Essen, Germany. Patients with
      PCOS were diagnosed according to the Rotterdam ESHRE/ASRM-sponsored PCOS
      Consensus Workshop Group. Afamin and diagnostic parameters of PCOS were
      determined at early follicular phase. Afamin concentrations were significantly
      higher in patients with PCOS than in controls (odds ratio (OR) for a 10 mg/ml
      increase in afamin=1.3, 95% CI=1.08-1.58). This difference vanished in a model
      adjusting for age, BMI, free testosterone index (FTI), and sex hormone-binding
      globulin (SHBG) (OR=1.05, 95% CI=0.80-1.38). In patients with PCOS, afamin
      correlated significantly with homeostatic model assessment-insulin resistance
      (HOMA-IR), fasting glucose, BMI, FTI, and SHBG (P<0.001), but in a multivariate
      linear model, only HOMA-IR remained significantly associated with afamin
      (P=0.001). No correlation was observed between afamin and androgens, LH, FSH,
      LH/FSH ratio, antral follicle count, ovarian volume, or anti-Mullerian hormone.
      In conclusion, elevated afamin values may indicate a state of oxidative stress
      and inflammation, strongly associated with IR and offering an indicator of
      impaired glucose tolerance in patients with PCOS irrespective of obesity. 

PMID- 24928912
TI  - 8th International Meeting of "Lorraine Pole of Cartilage Engineering". Foreword.

PMID- 24928910
TI  - Host factors determine differential disease progression after infection with nef
      deleted simian immunodeficiency virus.
AB  - Infection of macaques with live attenuated simian immunodeficiency virus (SIV)
      usually results in long-lasting efficient protection against infection with
      pathogenic immunodeficiency viruses. However, attenuation by deletion of
      regulatory genes such as nef is not complete, leading to a high viral load and
      fatal disease in some animals. To characterize immunological parameters and
      polymorphic host factors, we studied 17 rhesus macaques infected with attenuated
      SIVmac239DeltaNU. Eight animals were able to control viral replication, whereas
      the remaining animals (non-controllers) displayed variable set-point viral loads.
      Peak viral load at 2 weeks post-infection (p.i.) correlated significantly with
      set-point viral load (P<0.0001). CD4(+) T-cell frequencies differed significantly
      soon after infection between controllers and non-controllers. Abnormal B-cell
      activation previously ascribed to Nef function could already be observed in non
      controllers 8 weeks after infection despite the absence of Nef. Two non
      controllers developed an AIDS-like disease within 102 weeks p.i. Virus from these
      animals transmitted to naive animals replicated at low levels and the recipients
      did not develop immunodeficiency. This suggested that host factors determined
      differential viral load and subsequent disease course. Known Mhc class I alleles
      associated with disease progression in SIV WT infection only marginally
      influenced the viral load in Deltanef-infected animals. Protection from SIVmac251
      was associated with homozygosity for MHC class II in conjunction with a TLR7
      polymorphism and showed a trend with initial viral replication. We speculated
      that host factors whose effects were usually masked by Nef were responsible for
      the different disease courses in individual animals upon infection with nef
      deleted viruses. 

PMID- 24928913
TI  - Identification of new microRNAs targeting genes regulating the Pi/PPi balance in
      chondrocytes.
AB  - Osteoarthritis (OA) is a whole-joint disease characterized by cartilage
      degradation and mineralization associated with chondrocyte phenotype changes,
      subchondral bone sclerosis and mild synovial inflammation. The extracellular
      levels of inorganic phosphate (ePi) and pyrophosphate (ePPi) are major regulators
      of the mineralization process but also play a role in the maintenance of the
      differentiated chondrocyte phenotype. Four membrane proteins control the balance
      between ePi and ePPi: the transporters ANK (exporting PPi outside the cells) and
      PiT-1 (importing ePi into the cells), and the enzymes PC-1 (generating ePPi from
      nucleotides) and Tissue Non-specific Alkaline Phosphatase (TNAP, hydrolyzing ePPi
      into ePi). In the present work, we investigated the ability of specific microRNAs
      (miR) to modulate activity and level of the mRNA coding for the regulatory
      proteins of the ePi/ePPi balance in chondrocytes. The 4 following microRNAs,
      let7e, miR-9, miR-188 and miR-219, were selected by bioinformatics for their
      ability to putatively target the mRNA 3'UTRs of these regulators. In IL-1beta
      stimulated human chondrocytes, chosen as a model of differentiated phenotype loss
      implicating the PPi transporter ANK, miR-9, miR-188 and let7e levels increased.
      However, luciferase reporter assays and transient miR overexpression in the ATDC5
      chondrogenic cell line only support that miR-9 was a negative post
      transcriptional regulator of PC-1, Pit-1 and TNAP mRNAs. This suggests that miR-9
      could contribute to the acquirement of an altered chondrocyte phenotype by
      disrupting the ePi/ePPi balance.

PMID- 24928914
TI  - Synovial fluid levels of adipokines in osteoarthritis: Association with local
      factors of inflammation and cartilage maintenance.
AB  - The role of body weight in the pathogenesis of osteoarthritis (OA) - previously
      considered the sole factor in the association between obesity and OA - is being
      re-evaluated as the contribution of adiposity to the cartilage degenerative
      process becomes clearer. The current study has been undertaken to better
      understand the role of adipose-derived proteins, namely adipokines, in OA. For
      this purpose, we investigated in patients with OA the relationships between the
      joint levels of leptin, adiponectin and resistin and those of factors involved in
      inflammation and cartilage maintenance. The sandwich enzyme-linked immunosorbent
      assays were used to determine in the synovial fluid (SF) from 35 OA patients, the
      concentrations of adipokines, interleukin-6 (IL-6) and transforming growth factor
      beta (TGF-beta). The soluble form of leptin receptor (sOb-R) was also examined to
      evaluate the biological active free form of leptin. Correlation analysis indicate
      that IL-6 levels are positively related to the levels of resistin and
      adiponectin. Surprisingly, the free form of leptin, but not the total leptin, is
      negatively associated with IL-6. Beside, adiponectin is the single adipokine that
      is correlated with TGF-beta. Interestingly, a sexual dimorphism is observed in
      the study as correlations between adipokines and IL-6 or TGF-beta are found only
      with female OA patients. Taken together, these findings suggest that only
      adiponectin may contribute to the metabolic changes associated with OA. The three
      adipokines may also be involved in inflammation, but with opposite effects. Both
      resistin and adiponectin may exhibit pro-inflammatory activity while the free
      form of leptin may down-regulate the inflammation.

PMID- 24928916
TI  - Phosphate-induced mineralization of tracheal smooth muscle and cartilage cells.
AB  - BACKGROUND: During aging or various diseases, pathologic mineralization may occur
      in joints or in the vascular wall. This is due to the deposition of phosphate
      (Pi)-containing crystals into the extracellular matrix of articular chondrocytes
      or vascular smooth muscle cells. The mineralization ability of chondrocytes and
      smooth muscle cells of other tissue has not been investigated. OBJECTIVE: In this
      context, our work seeks to study the response induced by Pi on cartilage and
      smooth muscle cells from tracheal origin. METHODS: We have established a
      dissection procedure to harvest and isolate chondrocyte and smooth muscle cells
      from adult mouse trachea. Both cell types were then exposed to different
      concentrations of Pi (1, 3 or 5 mM) up to 14 days. Mineralization was evaluated
      by alizarin red staining, which identifies calcium deposition. The expression of
      genes characterizing the phenotypic identity of the cells and involved in the
      mineralization process was assessed by RT-qPCR. RESULTS: Treatment of tracheal
      chondrocytes and smooth muscle cells with increasing concentrations of Pi (3 and
      5 mM) induced mineralization as revealed by positive alizarin red staining as
      early as 7 days of culture. Moreover, gene expression analysis revealed profound
      phenotypic changes in both cell types and suggested they mineralize through TNAP
      independent or -dependent mechanisms, respectively. CONCLUSIONS: Our data
      indicate that, comparably to articular chondrocytes or vascular smooth muscles,
      chondrocyte and smooth muscle cells from the trachea are prone to mineralize
      under high-phosphate conditions.

PMID- 24928915
TI  - Increased internalization of Staphylococcus aureus and cytokine expression in
      human Wharton's jelly mesenchymal stem cells.
AB  - BACKGROUND: Although a large number of studies have documented the interaction of
      mesenchymal stem cells (MSCs) with cells of both the innate and adaptive immune
      systems, not much is known about how bacteria interact with MSCs and how this
      might influence MSCs behavior. In this study, we investigated the impact of
      Staphylococcus aureus (S. aureus), on viability and cytokines' production of
      human Wharton's jelly-MSCs (WJ-MSCs). OBJECTIVE: To investigate if WJ-MSCs: (1)
      internalize S. aureus; (2) are able to survive and (3) release immunomodulatory
      mediators after interaction with S. aureus. METHODS: WJ-MSCs were exposed to S.
      aureus at a multiplicity of infection (MOI) of 10:1 or 30:1 for different
      designed times. After interaction, intracellular bacteria were quantified as well
      as MSCs viability. Expression and cytokine-secretion were assessed using
      quantitative real-time PCR and ELISA. RESULTS: We found that the challenge of WJ
      MSCs with S. aureus resulted in increased internalization of S. aureus in a time
      dependent manner until six hours post-infection at either MOI of 10:1 and 30:1
      and in increased expression of IL-6 mRNA and secretion of TNF-alpha at six hours
      and nine hours post-infection (p<0.05). CONCLUSIONS: These results indicate that
      WJ-MSCs are able to internalize S. aureus and reveal a potential important
      function of these cells in the immune response.

PMID- 24928917
TI  - Donor's age dependent proliferation decrease of human bone marrow mesenchymal
      stem cells is linked to diminished clonogenicity.
AB  - While mesenchymal stem cells represent an interesting cell source for
      regenerative medicine, several points have to be investigated to improve their
      use in clinical, and in particular in the elderly population. This work studied
      the proliferation capacity of mesenchymal stem cells isolated from human bone
      marrow in function of donor's age. Doubling time after in vitro culture,
      clonogenicity and phenotype were analyzed in 17 samples ranging from 3 to 85
      years old (mean 47 +/- 27). Results showed an increase in the doubling time for
      cell coming from old donor compared to cells coming from young ones. This was
      accompanied by a decrease in clonogenicity while no changes were observe in cell
      phenotype. In conclusion, this study showed an effect of donor's age on the
      proliferation capacity of mesenchymal stem cells isolated from bone marrow that
      was correlated to a decrease in clonogenicity. The comprehension of molecular
      mechanism involved in this process could help to improve the clinical application
      of mesenchymal stem cells.

PMID- 24928918
TI  - Gene screening of Wharton's jelly derived stem cells.
AB  - Stem cells are the most powerful candidate for the treatment of various diseases.
      Suitable stem cell source should be harvested with minimal invasive procedure,
      found in great quantity, and transplanted with no risk of immune response and
      tumor formation. Fetal derived stem cells have been introduced as an excellent
      alternative to adult and embryonic stem cells use, but unfortunately, their
      degree of "stemness" and molecular characterization is still unclear. Several
      studies have been performed deciphering whether fetal stem cells meet the needs
      of regenerative medicine. We believe that a transcriptomic screening of Wharton's
      jelly stem cells will bring insights on cell population features.

PMID- 24928919
TI  - Chitosan/hydroxyapatite hybrid scaffold for bone tissue engineering.
AB  - BACKGROUND: To favor regeneration following critical bone defect, a combination
      of autologous bone graft and biomaterials is currently used. Major drawbacks of
      such techniques remain the availability of the autologous material and the second
      surgical site, inducing pain and morbidity. OBJECTIVE: Our aim was to investigate
      the biocompatibility in vitro of three dimensions hybrid biodegradable scaffolds
      combining osteoconductive properties of hydroxyapatite and anti-inflammatory
      properties of chitosan. METHODS: Hybrid scaffolds were characterized by
      microscopic observations, equilibrium swelling ratio and overtime weight loss
      measurements. In vitro studies were performed using primary human bone cells
      cultured for 7, 14 and 21 days. Cell viability, proliferation, morphology and
      differentiation through alkaline phosphatase (ALP) activity measurement were
      assessed. RESULTS: Characterization of our scaffolds demonstrated porous,
      hydrophilic and biodegradable characteristics. In vitro studies showed that these
      scaffolds have induced slight decrease in cell death and proliferation comparing
      to the culture plastic substrate control condition, as well as increased short
      term osteoinductive properties. CONCLUSIONS: In this study, we have provided
      evidence that our hybrid hydroxyapatite/chitosan scaffolds could be suitable for
      bone filling.

PMID- 24928920
TI  - Age-related alterations in TGF beta signaling as a causal factor of cartilage
      degeneration in osteoarthritis.
AB  - BACKGROUND: Age is the most important risk factor for primary osteoarthritis
      (OA). Members of the TGF-beta superfamily play a crucial role in chondrocyte
      differentiation and maintenance of healthy articular cartilage. OBJECTIVE: We
      have investigated whether age-related changes in TGF-beta superfamily signaling
      components play a role in the relationship between OA-related cartilage
      degradation and aging. MATERIAL AND METHODS: The relationship between age, OA and
      TGF-beta superfamily signaling was studied using murine experimental OA models,
      aging mice, bovine articular cartilage and human OA cartilage. The effects of TGF
      beta on cartilage homeostasis was studied with immunohistochemistry, Q-RT-PCR and
      signaling pathway analysis with Western blotting and the application of specific
      TGF-beta inhibitors. RESULTS: We have found that TGF-beta loses its protective
      effects in old cartilage. Moreover, we found that on chondrocytes, TGF-beta not
      only signals via the canonical type I receptor ALK5 (TGFBR1) but also via the
      ALK1 (ACVRL1) receptor. Remarkably, signaling via ALK5 (Smad2/3 route) results in
      protective while ALK1 signaling (Smad1/5/8 route) results in deleterious
      responses in articular chondrocytes. In cartilage of aging mice it was detected
      that the ALK1/ALK5 ratio is significantly increased, favoring TGF-beta signaling
      via the Smad1/5/8 route, inducing changes in chondrocyte differentiation and
      matrix metalloproteinase-13 (MMP-13) expression. Moreover, human OA cartilage
      showed a significant correlation between ALK1 and MMP-13 expression. Since in
      mice aging and OA in often goes hand in hand, we also analyzed age-related
      expression of TGF-beta superfamily related signaling molecules in healthy bovine
      cartilage in an age range from 6 months to 14 years. In this cohort of aging
      cartilage, we found that mainly signaling receptors determining the Smad2/3
      pathway were decreased with age while Smad1/5/8-related signaling molecules did
      not alter, confirming our findings in aging mice. CONCLUSIONS: Old cartilage
      appears to be less protected by TGF-beta and shows significant alterations in TGF
      beta signaling pathways. Loss of the protective Smad2/3 pathway during aging can
      provide an explanation for the relationship between OA and aging.

PMID- 24928921
TI  - Fenofibrate vs pioglitazone: Comparative study of the anti-arthritic potencies of
      PPAR-alpha and PPAR-gamma agonists in rat adjuvant-induced arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is characterized by synovial hyperplasia,
      inflammatory infiltration, cartilage destruction and juxta-articular as well as
      generalized bone demineralization. Peroxisome proliferator-activated receptors
      (PPARs) are members of the nuclear hormone receptor superfamily which behave as
      ligand-activated transcription factors in response to endogenous fatty acids and
      eicosanoids or isotype selective synthetic compounds as fibrates and
      thiazolidinediones. Beyond their key role in lipid metabolism, increased evidence
      has shown a role of the three isotypes in inflammatory modulation. We and others
      demonstrated previously that PPAR-gamma agonists reduced the severity of
      experimental polyarthritis and the overall inflammatory-induced bone loss.
      OBJECTIVE: To compare the anti-arthritic potencies of a PPAR-alpha agonist
      (fenofibrate, a lipid lowering drug) and a PPAR-gamma agonist (pioglitazone,
      formerly used as an antidiabetic drug) in rat adjuvant-induced arthritis.
      METHODS: Male Lewis rats were sensitized by an intra-dermal injection of 1 mg
      complete Freund's adjuvant at the basis of the tail and were treated orally for
      21 days with fenofibrate 100 mg/kg/day (FENO) or pioglitazone 30 mg/kg/day (PIO),
      or with vehicle only. Arthritis severity was evaluated by clinical observations
      (oedema, clinical score, body weight). Global and femoral bone mineral density
      (BMD), femoral bone mineral content (BMC) were measured by dual-energy X-ray
      absorptiometry (DEXA) before sensitization and at day 20. Synovial mRNA levels of
      IL-1beta and IL-6 were determined by real-time RT-PCR. RESULTS: Administration of
      fenofibrate (100mg/kg/d) and pioglitazone (30 mg/kg/d) significantly reduced
      hindpaw oedema and arthritis score. Treatment with fenofibrate exerted a better
      effect on clinical scoring. DEXA analysis revealed that pioglitazone and
      fenofibrate treatment to a greater extent, reduced inflammatory-bone loss and
      increased BMD versus vehicle-treated rats. Finally, we demonstrated that both
      agonists decreased synovial expression of IL-1beta and IL-6. CONCLUSION:
      Pioglitazone and fenofibrate decreased arthritis severity in adjuvant-induced
      arthritis. Both agonists partially protected animals from inflammatory induced
      bone loss.

PMID- 24928922
TI  - Decrease in red blood cell deformability is associated with a reduction in RBC
      NOS activation during storage.
AB  - During storage, red blood cells (RBC) become more susceptible to hemolysis and it
      has also been shown that RBC deformability, which is influenced by RBC nitric
      oxide synthase (RBC-NOS) activity, decreases during blood storage while a
      correlation between these two parameters under storage conditions has not been
      investigated so far. Therefore, blood from 15 male volunteers was anticoagulated,
      leuko-reduced and stored as either concentrated RBC or RBC diluted in saline
      adenine-glucose-mannitol (SAGM) for eight weeks at 4 degrees C and results were
      compared to data obtained from freshly drawn blood. During storage, decrease of
      RBC deformability was related to increased mean cellular volume and increased
      cell lysis but also to a decrease in RBC-NOS activation. The changes were more
      pronounced in concentrated RBC than in RBC diluted in SAGM suggesting that the
      storage method affects the quality of blood. These data shed new light on
      mechanisms underlying the phenomenon of storage lesion and reveal that RBC-NOS
      activation and possibly nitric oxide production in RBC are key elements that are
      influenced by storage and in turn alter deformability. Further studies should
      therefore also focus on improving these parameters during storage to improve the
      quality of stored blood with respect to blood transfusion. 

PMID- 24928923
TI  - Battle against the odds: win with effort, attitude, and perseverance!

PMID- 24928925
TI  - Phytobezoar leading to gastric outlet obstruction in a patient with diabetes.
AB  - Gastroparesis is a condition which results in delayed gastric emptying without
      gastric outflow tract obstruction. Gastrointestinal involvement in diabetes can
      present in various forms such as oesophageal dysmotility, gastro-oesophageal
      reflux disease, gastroparesis, enteropathy, non-alcoholic fatty liver disease and
      glycogenic hepatopathy. Gastroparesis is the most common gastric motility
      disorder complicating long-standing diabetes. It can sometimes lead to mechanical
      obstruction as a result of formation of bezoars. Phytobezoars are the most common
      type of bezoar and are composed of indigestible food, vegetable fibre or seeds.
      Poor pyloric function and decreased acid formation predisposes phytobezoars
      formation in patients with diabetic gastroparesis. An 80-year-old patient with
      diabetes in our presentation developed gastric outlet obstruction due to
      impaction of phytobezoar over the pylorus. 

PMID- 24928924
TI  - BEM46 shows eisosomal localization and association with tryptophan-derived auxin
      pathway in Neurospora crassa.
AB  - BEM46 proteins are evolutionarily conserved, but their functions remain elusive.
      We reported previously that the BEM46 protein in Neurospora crassa is targeted to
      the endoplasmic reticulum (ER) and is essential for ascospore germination. In the
      present study, we established a bem46 knockout strain of N. crassa. This
      Deltabem46 mutant exhibited a level of ascospore germination lower than that of
      the wild type but much higher than those of the previously characterized bem46
      overexpressing and RNA interference (RNAi) lines. Reinvestigation of the RNAi
      transformants revealed two types of alternatively spliced bem46 mRNA; expression
      of either type led to a loss of ascospore germination. Our results indicated that
      the phenotype was not due to bem46 mRNA downregulation or loss but was caused by
      the alternatively spliced mRNAs and the peptides they encoded. Using the N.
      crassa ortholog of the eisosomal protein PILA from Aspergillus nidulans, we
      further demonstrated the colocalization of BEM46 with eisosomes. Employing the
      yeast two-hybrid system, we identified a single interaction partner: anthranilate
      synthase component II (encoded by trp-1). This interaction was confirmed in vivo
      by a split-YFP (yellow fluorescent protein) approach. The Deltatrp-1 mutant
      showed reduced ascospore germination and increased indole production, and we used
      bioinformatic tools to identify a putative auxin biosynthetic pathway. The genes
      involved exhibited various levels of transcriptional regulation in the different
      bem46 transformant and mutant strains. We also investigated the indole production
      of the strains in different developmental stages. Our findings suggested that the
      regulation of indole biosynthesis genes was influenced by bem46 overexpression.
      Furthermore, we uncovered evidence of colocalization of BEM46 with the neutral
      amino acid transporter MTR. 

PMID- 24928926
TI  - Peripheral embolisation after an abdominal massage.
AB  - A 65-year-old man presented with a history of acute onset pain in toes of the
      right foot immediately after an abdominal massage by a 'local healer'. General
      physical examination and systemic examination were normal except for
      discolouration of the fourth and fifth toes and cold toes. Investigations
      including complete blood count, erythrocyte sedimentation rate, renal function
      tests, liver profile, lipid profile, antinuclear antibody, antineutrophil
      cytoplasmic antibody, ECG, chest X-ray, ultrasound abdomen, cardiac
      echocardiography, lower limb Doppler and CT scan of the abdomen were normal. The
      patient was treated with regular heparin infusion, aspirin and tramadol. Recovery
      was complete in 5 days.

PMID- 24928927
TI  - Solid blue dot tumour: minor salivary gland acinic cell carcinoma.
AB  - Acinic cell adenocarcinoma (ACC) is a low-grade malignant salivary neoplasm that
      constitutes approximately 17% of all primary salivary gland malignancies. In the
      head and neck region, the parotid gland is the predominant site of origin and ACC
      is usually more frequent in women than men. Previous radiation exposure and
      familial predisposition are some of the risk factors for ACC. ACCs rarely involve
      minor salivary glands constituting only 13-17% of all minor salivary gland
      tumours. Generally, a slowly enlarging mass lesion in the tail of the parotid
      gland is the most frequent presentation. ACC has a significant tendency to recur,
      metastasise and may have an aggressive evolution. Therefore, a long-term follow
      up is mandatory after treatment. Here we report the case of a woman in her 60s
      with an ACC in association with the labial minor salivary gland, presenting in
      the post-treatment period of squamous cell carcinoma of the tongue. 

PMID- 24928928
TI  - Presurgical nasal moulding in a neonate with cleft lip.
AB  - The concept of presurgical nasoalveolar moulding (PNM) was developed to improve
      the aesthetic result of surgically corrected cleft lip. This paper presents the
      method of fabrication of PNM appliance and the case of a 30-day-old neonate with
      unilateral cleft lip in whom nasal moulding was performed. Treatment was
      initiated at 30 days and continued for 60 days after which the surgical
      correction of cleft lip was performed. Significant improvement in aesthetics and
      symmetry of the nose was achieved at the end of the treatment.

PMID- 24928929
TI  - Neonatal Marfan syndrome: a successful early multidisciplinary approach.
AB  - Marfan syndrome (MFS) is a genetic disorder of the connective tissue which rarely
      manifests in the neonatal period and has an ominous prognosis. A case of a first
      female offspring of healthy parents is described here. The pregnancy was
      uneventful and the mother had a term caesarean delivery. At birth, some
      dysmorphic signs became apparent, such as loose redundant skin, dolichocephaly,
      frontal bossing, deeply sunken eyes, micrognathia, contractures of the elbows,
      arachnodactyly and hip dysplasia. The echocardiogram showed a mitral and
      tricuspid valve regurgitation and a long aortic arch. The diagnosis of neonatal
      MFS came forward and genetic studies revealed a de novo mutation in the fibrillin
      1 (FBN1) gene. At 6 months, due to a progressive worsening of the cardiac
      pathology, she was submitted to mitral valvuloplasty. She is now 2 years and 10
      months old, which is a remarkable feat for a child suffering from this condition.

PMID- 24928930
TI  - Neurodegenerative disorder masquerading as psychosis in a forensic psychiatry
      setting.
AB  - A man presenting in his 50s, following conviction for a non-violent crime, to
      forensic psychiatric services, and then to a neuropsychiatry service with an
      unusual presentation of psychosis: second person auditory hallucinations,
      grandiose delusions and somatic delusions. Detailed collateral and family history
      revealed a background of progressive cognitive deficit and a family history of
      motor neuron disease. MRI of the brain revealed asymmetrical parieto-occipital
      volume loss and genetic testing demonstrated a pathogenic expansion of the
      chromosome 9 open reading frame 72 (C9ORF72) gene consistent with familial
      frontotemporal dementia caused by a hexanucleotide repeat expansion at C9ORF72, a
      recently discovered cause of familial frontotemporal dementia/motor neuron
      disease. This form of frontotemporal dementia should be considered as an
      important potential differential diagnosis for patients presenting with psychotic
      symptoms in later life, in whom a detailed family history and thorough cognitive
      assessment is essential. 

PMID- 24928931
TI  - The child with spontaneous recurrent bleeding in the eye.
AB  - Juvenile xanthogranuloma is a self-limiting dermatological condition
      characterised by spontaneous hyphaema due to uveal involvement causing
      neovascularisation. Recurrent hyphaema in a child should alert the clinician
      towards this rare diagnosis. Appropriate investigations and treatment should be
      directed towards treating this possible diagnosis associated with neovascular
      glaucoma where routine filtering surgeries may be associated with several
      complications. 

PMID- 24928932
TI  - Transient acute adrenal insufficiency associated with adenovirus serotype 40
      infection.
AB  - We present an instance of a 6-year-old boy who was admitted with adenovirus
      infection and developed transient acute adrenal insufficiency, which required
      supplementation with glucocorticoids and mineralocorticoids for 8 weeks.
      Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We
      could not find any similar reported case in medical literature. We hope our case
      would add to the existing knowledge of adenoviral complications in paediatric
      patients. 

PMID- 24928933
TI  - Peritoneal inclusion cysts in pregnancy, a diagnostic challenge.
AB  - A cystic pelvic mass detected during pregnancy is not uncommon, but can be a
      diagnostic challenge. Most of these pelvic masses are benign ovarian cysts and
      resolve spontaneously. However, rare non-ovarian causes can complicate the
      diagnostic and therapeutic management. In this report an unusual case is
      presented of a 27-year-old pregnant woman with an atypical multicystic lesion in
      the pelvis, seen on routine first trimester ultrasound. A laparoscopic
      exploration was performed to rule out ovarian malignancy, and after histological
      analysis she was diagnosed with peritoneal inclusion cysts. The diagnostic and
      therapeutic challenges inherent to this rare non-ovarian disease are addressed in
      this case report. 

PMID- 24928934
TI  - Green urine in a postoperative patient.

PMID- 24928935
TI  - Pseudointernuclear ophthalmoplegia as a presenting feature of ocular myasthenia
      gravis.

PMID- 24928936
TI  - Increased serum CXCL1 and CXCL5 are linked to obesity, hyperglycemia, and
      impaired islet function.
AB  - Proinflammatory cytokines are thought to play a significant role in the
      pathogenesis of type 2 diabetes (T2D) and are elevated in the circulation even
      before the onset of the disease. However, the full complement of cytokines
      involved in the development of T2D is not known. In this study, 32 serum
      cytokines were measured from diabetes-prone BKS.Cg-m+/+Lepr(db)/J (db/db) mice
      and heterozygous age-matched control mice at 5 weeks (non-diabetic/non-obese), 6
      7 weeks (transitional-to-diabetes), or 11 weeks (hyperglycemic/obese) and then
      correlated with body weight, blood glucose, and fat content. Among these 32
      cytokines, C-X-C motif ligand 1 (CXCL1) showed the greatest increase (+78%) in
      serum levels between db/db mice that were hyperglycemic (blood glucose: 519+/-23
      mg/dl, n=6) and those that were non-hyperglycemic (193+/-13 mg/dl, n=8).
      Similarly, increased CXCL1 (+68%) and CXCL5 (+40%) were associated with increased
      obesity in db/db mice; note that these effects could not be entirely separated
      from age. We then examined whether islets could be a source of these chemokines.
      Exposure to cytokines mimicking low-grade systemic inflammation (10 pg/ml
      IL1beta+20 pg/ml IL6) for 48 h upregulated islet CXCL1 expression by 53+/-3-fold
      and CXCL5 expression by 83+/-10-fold (n=4, P<0.001). Finally, overnight treatment
      with the combination of CXCL1 and CXCL5 at serum levels was sufficient to produce
      a significant decrease in the peak calcium response to glucose stimulation,
      suggesting reduced islet function. Our findings demonstrated that CXCL1 and CXCL5
      i) are increased in the circulation with the onset of T2D, ii) are produced by
      islets under stress, and iii) synergistically affect islet function, suggesting
      that these chemokines participate in the pathogenesis of T2D. 

PMID- 24928937
TI  - Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and
      angiogenesis.
AB  - We have shown in vitro that thyroid hormones (THs) regulate the balance between
      proliferation and apoptosis of T lymphoma cells. The effects of THs on tumor
      development have been studied, but the results are still controversial. Herein,
      we show the modulatory action of thyroid status on the in vivo growth of T
      lymphoma cells. For this purpose, euthyroid, hypothyroid, and hyperthyroid mice
      received inoculations of EL4 cells to allow the development of solid tumors.
      Tumors in the hyperthyroid animals exhibited a higher growth rate, as evidenced
      by the early appearance of palpable solid tumors and the increased tumor volume.
      These results are consistent with the rate of cell division determined by
      staining tumor cells with carboxyfluorescein succinimidyl ester. Additionally,
      hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ
      significantly from the euthyroid controls with respect to these parameters.
      Additionally, only tumors from hyperthyroid animals had increased expression
      levels of proliferating cell nuclear antigen and active caspase 3. Differential
      expression of cell cycle regulatory proteins was also observed. The levels of
      cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals,
      whereas the cell cycle inhibitors p16/INK4A (CDKN2A) and p27/Kip1 (CDKN1B) and
      the tumor suppressor p53 (TRP53) were increased in hypothyroid mice. Intratumoral
      and peritumoral vasculogenesis was increased only in hyperthyroid mice.
      Therefore, we propose that the thyroid status modulates the in vivo growth of EL4
      T lymphoma through the regulation of cyclin, cyclin-dependent kinase inhibitor,
      and tumor suppressor gene expression, as well as the stimulation of angiogenesis.

PMID- 24928938
TI  - Mechanisms of PEDF-mediated protection against reactive oxygen species damage in
      diabetic retinopathy and neuropathy.
AB  - Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging
      to the serpin family. PEDF can stimulate several physiological processes such as
      angiogenesis, cell proliferation, and survival. Oxidative stress plays an
      important role in the occurrence of diabetic retinopathy (DR), which is the major
      cause of blindness in young diabetic adults. PEDF plays a protective role in DR
      and there is accumulating evidence of the neuroprotective effect of PEDF. In this
      paper, we review the role of PEDF and the mechanisms involved in its
      antioxidative, anti-inflammatory, and neuroprotective properties. 

PMID- 24928939
TI  - Gender- and region-specific alterations in bone metabolism in Scarb1-null female
      mice.
AB  - A positive correlation between plasma levels of HDL and bone mass has been
      reported by epidemiological studies. As scavenger receptor class B, type I (SR
      BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently
      characterized bone metabolism in Scarb1-null mice. These mice display high
      femoral bone mass associated with enhanced bone formation. As gender differences
      have been reported in HDL metabolism and SR-BI function, we investigated gender
      specific bone alterations in Scarb1-null mice by microtomography and histology.
      We found 16% greater relative bone volume and 39% higher bone formation rate in
      the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen
      in males, indicating gender- and region-specific differences in skeletal
      phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma
      levels, were increased in both Scarb1-null genders, the latter being concurrent
      to impaired corticosterone response to fasting. Plasma levels of estradiol did
      not differ between null and WT females, suggesting that the estrogen metabolism
      alteration is not relevant to the higher vertebral bone mass in female Scarb1
      null mice. Constitutively, high plasma levels of leptin along with 2.5-fold
      increase in its expression in white adipose tissue were measured in female Scarb1
      null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin
      promoted osteoblast differentiation as evidenced by increased gene expression of
      osterix and collagen type I alpha. Our results suggest that hyperleptinemia may
      account for the gender-specific high bone mass seen in the vertebrae of female
      Scarb1-null mice. 

PMID- 24928940
TI  - Endocrine regulation of airway contractility is overlooked.
AB  - Asthma is a prevalent respiratory disorder triggered by a variety of inhaled
      environmental factors, such as allergens, viruses, and pollutants. Asthma is
      characterized by an elevated activation of the smooth muscle surrounding the
      airways, as well as a propensity of the airways to narrow excessively in response
      to a spasmogen (i.e. contractile agonist), a feature called airway
      hyperresponsiveness. The level of airway smooth muscle (ASM) activation is
      putatively controlled by mediators released in its vicinity. In asthma, many
      mediators that affect ASM contractility originate from inflammatory cells that
      are mobilized into the airways, such as eosinophils. However, mounting evidence
      indicates that mediators released by remote organs can also influence the level
      of activation of ASM, as well as its level of responsiveness to spasmogens and
      relaxant agonists. These remote mediators are transported through circulating
      blood to act either directly on ASM or indirectly via the nervous system by
      tuning the level of cholinergic activation of ASM. Indeed, mediators generated
      from diverse organs, including the adrenals, pancreas, adipose tissue, gonads,
      heart, intestines, and stomach, affect the contractility of ASM. Together, these
      results suggest that, apart from a paracrine mode of regulation, ASM is subjected
      to an endocrine mode of regulation. The results also imply that defects in organs
      other than the lungs can contribute to asthma symptoms and severity. In this
      review, I suggest that the endocrine mode of regulation of ASM contractility is
      overlooked. 

PMID- 24928942
TI  - Editorial.

PMID- 24928944
TI  - Molecular pathways: PI3K pathway phosphatases as biomarkers for cancer prognosis
      and therapy.
AB  - Cancer research has seen tremendous changes over the past decade. Fast progress
      in sequencing technology has afforded us with landmark genetic alterations, which
      had immediate impact on clinical science and practice by pointing to new kinase
      targets, such as phosphoinositide 3-kinase (PI3K), the EGF receptor, or BRAF. The
      PI3K pathway for growth control has emerged as a prime example for both oncogene
      activation and tumor suppressor loss in cancer. Here, we discuss how therapy
      using PI3K pathway inhibitors could benefit from information on specific
      phosphatases, which naturally antagonize the kinase targets. This PI3K pathway is
      found mutated in most cancer types, including prostate, breast, colon, and brain
      tumors. The tumor-suppressing phosphatases operate at two levels. Lipid-level
      phosphatases, such as PTEN and INPP4B, revert PI3K activity to keep the lipid
      second messengers inactive. At the protein level, PHLPP1/2 protein phosphatases
      inactivate AKT kinase, thus antagonizing mTOR complex 2 activity. However, in
      contrast with their kinase counterparts the phosphatases are unlikely drug
      targets. They would need to be stimulated by therapy and are commonly deleted and
      mutated in cancer. Yet, because they occupy critical nodes in preventing cancer
      initiation and progression, the information on their status has tremendous
      potential in outcome prediction, and in matching the available kinase inhibitor
      repertoire with the right patients. Clin Cancer Res; 20(12); 3057-63. (c)2014
      AACR. 

PMID- 24928947
TI  - Retraction: molecular analysis of non-small cell lung cancer identifies subsets
      with different sensitivity to insulin-like growth factor i receptor inhibition.

PMID- 24928946
TI  - CHFR promoter methylation indicates poor prognosis in stage II microsatellite
      stable colorectal cancer.
AB  - PURPOSE: Data on the prognostic significance of promoter CpG island methylation
      in colorectal cancer (CRC) are conflicting, possibly due to associations between
      methylation and other factors affecting survival such as genetic alterations and
      use of adjuvant therapy. Here, we examine the prognostic impact of promoter
      methylation in patients with CRC treated with surgery alone in the context of
      microsatellite instability (MSI), BRAF and KRAS mutations. EXPERIMENTAL METHODS:
      One hundred and seventy-three CRCs were analyzed for promoter methylation of 19
      tumor suppressor and DNA repair genes, the CpG island methylator phenotype
      (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations.
      RESULTS: Unsupervised hierarchical clustering based on methylation status of 19
      genes revealed three subgroups: cluster 1 [CL1, 57% (98/173) of CRCs], cluster 2
      [CL2, 25% (43/173) of CRCs], and cluster 3 [CL3, 18% (32/173) of CRCs]. CL3 had
      the highest methylation index (0.25, 0.49, and 0.69, respectively, P = <0.01) and
      was strongly associated with CIMP (P < 0.01). Subgroup analysis for tumor stage,
      MSI, and BRAF status showed no statistically significant differences in survival
      between CL1, CL2, and CL3 nor between CIMP and non-CIMP CRCs. Analyzing genes
      separately revealed that CHFR promoter methylation was associated with a poor
      prognosis in stage II, microsatellite stability (MSS), BRAF wild-type (WT) CRCs:
      multivariate Cox proportional HR = 3.89 [95% confidence interval (CI), 1.58-9.60,
      P < 0.01; n = 66] and HR = 2.11 (95% CI, 0.95-4.69, P = 0.068, n = 136) in a
      second independent population-based study. CONCLUSIONS: CHFR promoter CpG island
      methylation, which is associated with MSI, also occurs frequently in MSS CRCs and
      is a promising prognostic marker in stage II, MSS, BRAF WT CRCs.

PMID- 24928941
TI  - Circadian regulation of metabolism.
AB  - In association with sleep-wake and fasting-feeding cycles, organisms experience
      dramatic oscillations in energetic demands and nutrient supply. It is therefore
      not surprising that various metabolic parameters, ranging from the activity
      status of molecular energy sensors to circulating nutrient levels, oscillate in
      time-of-day-dependent manners. It has become increasingly clear that rhythms in
      metabolic processes are not simply in response to daily environmental/behavioral
      influences, but are driven in part by cell autonomous circadian clocks. By
      synchronizing the cell with its environment, clocks modulate a host of metabolic
      processes in a temporally appropriate manner. The purpose of this article is to
      review current understanding of the interplay between circadian clocks and
      metabolism, in addition to the pathophysiologic consequences of disruption of
      this molecular mechanism, in terms of cardiometabolic disease development. 

PMID- 24928945
TI  - Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness
      in ER+ breast cancer.
AB  - PURPOSE: Estrogen receptor-alpha (ERalpha)-targeted therapies including tamoxifen
      (TAM) or Faslodex (ICI) are used to treat ER(+) breast cancers. Up to 50% of
      tumors will acquire resistance to these interventions. Autophagy has been
      implicated as a major driver of antiestrogen resistance. We have explored the
      ability of hydroxychloroquine (HCQ), which inhibits autophagy, to affect
      antiestrogen responsiveness. EXPERIMENTAL DESIGN: TAM-resistant MCF7-RR and ICI
      resistant/TAM cross-resistant LCC9 ER(+) breast cancer cells were injected into
      mammary fat pads of female athymic mice and treated with TAM and/or ICI in
      combination with oral low-dose HCQ. RESULTS: We show that HCQ can increase
      antiestrogen responsiveness in MCF7-RR and LCC9 cells and tumors, likely through
      the inhibition of autophagy. However, the combination of ICI+HCQ was less
      effective than HCQ alone in vivo, unlike the TAM+HCQ combination. Antiestrogen
      treatment stimulated angiogenesis in tumors but did not prevent HCQ
      effectiveness. The lower efficacy of ICI+HCQ was associated with ICI effects on
      cell-mediated immunity within the tumor microenvironment. The mouse chemokine KC
      (CXCL1) and IFNgamma were differentially regulated by both TAM and ICI
      treatments, suggesting a possible effect on macrophage development/activity.
      Consistent with these observations, TAM+HCQ treatment increased tumor CD68(+)
      cells infiltration, whereas ICI and ICI+HCQ reduced peripheral tumor macrophage
      content. Moreover, macrophage elimination of breast cancer target cells in vitro
      was reduced following exposure to ICI. CONCLUSION: HCQ restores antiestrogen
      sensitivity to resistant tumors. Moreover, the beneficial combination of TAM+HCQ
      suggests a positive outcome for ongoing neoadjuvant clinical trials using this
      combination for the treatment of ER(+) ductal carcinoma in situ lesions.

PMID- 24928948
TI  - A prospective randomized trial of single- or dual-chamber implantable
      cardioverter-defibrillators to minimize inappropriate shock risk in primary
      sudden cardiac death prevention.
AB  - AIMS: Dual-chamber implantable cardioverter-defibrillators (ICDs) may improve
      specificity and reduce the risk of inappropriate shocks, and enhance atrial
      arrhythmia (AT/AF) detection to permit stroke prevention compared with single
      chamber ICDs, but at additional expense and risk. METHODS AND RESULTS: Patients
      (n = 100) receiving primary prevention ICDs at two USA and two Israeli centres
      were randomized to dual-chamber or single-chamber devices between December 2008
      and December 2010 and were followed for 1 year. Programming in both groups
      included: delayed detection to avoid therapy for non-sustained episodes; high
      detection cut-off rates to avoid treating slower, better tolerated arrhythmias;
      minimized right ventricular pacing; and routine use of supraventricular
      ventricular tahcycardia discriminators and antitachycardia pacing. The primary
      outcome was the proportion of patients with inappropriate shocks. One patient in
      each group (2%) received inappropriate shocks (P = 1.00). Death occurred in two
      patients in the single-chamber arm, and in none of the patients in the dual
      chamber arm (P = 0.15). New AT/AF was detected in 12 patients (24%) in the dual
      chamber group, vs. no patients in the single-chamber group (P < 0.001). Among US
      participants, the mean cost of dual- vs. single-chamber ICD implantation was $16
      579 vs. $14 249, respectively (P < 0.001); there was no difference in the quality
      of life (EQ-5D index difference 0.013, P = 0.769; EQ VAS difference 3.3, P =
      0.49). CONCLUSION: When optimal programming is utilized, inappropriate shocks are
      rare in primary prevention patients with both single- and dual-chamber ICDs. The
      routine use of dual-chamber ICDs increases the expense without reducing
      inappropriate shocks or improving the quality of life at 1 year. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00787800.

PMID- 24928949
TI  - Author reply: To PMID 24446511.

PMID- 24928950
TI  - In cryoballoon pulmonary vein isolation there is no correlation between biomarker
      release indicating myocardial necrosis and cumulative freezing time.

PMID- 24928951
TI  - Characteristics of TRK-130 (Naltalimide), a novel opioid ligand, as a new
      therapeutic agent for overactive bladder.
AB  - We characterized TRK-130 (N-[(5R,6R,14S)-17-(cyclopropylmethyl)-4,5-epoxy-3,14
      dihydroxymorphinan-6-yl]phthalimide; naltalimide), an opioid ligand, to clarify
      the therapeutic potential for overactive bladder (OAB). In radioligand-binding
      assays with cells expressing human u-opioid receptors (MORs), delta-opioid
      receptors (DORs), or kappa-opioid receptors (KORs), TRK-130 showed high
      selectivity for MORs (Ki for MORs, DORs, and KORs = 0.268, 121, and 8.97 nM,
      respectively). In a functional assay (cAMP accumulation) with cells expressing
      each human opioid receptor subtype, TRK-130 showed potent but partial agonistic
      activity for MORs [EC50 (Emax) for MORs, DORs, and KORs = 2.39 nM (66.1%), 26.1
      nM (71.0%), and 9.51 nM (62.6%), respectively]. In isovolumetric rhythmic bladder
      contractions (RBCs) in anesthetized guinea pigs, TRK-130 dose-dependently
      prolonged the shutdown time (the duration of complete cessation of the bladder
      contractions) (ED30 = 0.0034 mg/kg i.v.) without affecting amplitude of RBCs.
      Furthermore, TRK-130 ameliorated formalin-induced frequent urination at doses of
      higher than 0.01 mg/kg p.o. in guinea pigs under the freely moving condition.
      Meanwhile, TRK-130 showed only a negligible effect on the gastrointestinal
      transit at doses of up to 10 mg/kg s.c. in mice. These results indicate that TRK
      130 is a potent and selective human MOR partial agonist without undesirable
      opioid adverse effects such as constipation and enhances the storage function by
      suppressing the afferent limb of the micturition reflex pathway, suggesting that
      TRK-130 would be a new therapeutic agent for OAB. 

PMID- 24928952
TI  - Ankle dorsiflexor muscle size, composition and force with ageing and chronic
      obstructive pulmonary disease.
AB  - Loss of skeletal muscle strength is a well-recognized feature of ageing and
      chronic obstructive pulmonary disease (COPD). Reductions in muscle size provide
      only a partial explanation for this loss of strength, and additional contributory
      factors remain undetermined. We hypothesized that reductions in skeletal muscle
      strength, as measured in the ankle dorsiflexor muscles, would be reduced with
      ageing and COPD as a result of changes in both size and composition of the
      tibialis anterior muscle. Twenty healthy young subjects, 18 healthy elderly
      subjects and 17 patients with COPD were studied. Ankle dorsiflexor muscle
      strength was assessed by maximal voluntary contraction (ADMVC) and 100 Hz
      supramaximal electrical stimulation of the peroneal nerve (100 HzAD). Tibialis
      anterior cross-sectional area (TACSA) and composition, as assessed by echo
      intensity (TAEI), were measured using ultrasonography. Despite a lack of
      differences in TACSA between groups, ADMVC and 100 HzAD were significantly
      reduced in COPD patients compared with both healthy elderly and healthy young
      subjects, when expressed as absolute values and when normalized to TACSA (P <
      0.01). The TAEI was, however, higher in COPD patients compared with healthy
      elderly (P = 0.025) and healthy young subjects (P = 0.0008), suggesting increased
      levels of non-contractile tissue. Across all participants, ADMVC and 100 HzAD
      correlated positively with TACSA (r = 0.78, P < 0.0001) and negatively with TAEI
      (r = -0.46, P < 0.0005). The variance in 100 HzAD was best explained with a
      regression model incorporating TACSA, TAEI, age and COPD status (r(2) = 0.822, P
      = 0.001). These data demonstrate that the loss of skeletal muscle strength in
      COPD is related to changes in muscle composition, with infiltration of non
      contractile tissue beyond that seen during normal ageing.

PMID- 24928953
TI  - Impact of endothelin blockade on acute exercise-induced changes in blood flow and
      endothelial function in type 2 diabetes mellitus.
AB  - Positive vascular effects of exercise training are mediated by acute increases in
      blood flow. Type 2 diabetes patients show attenuated exercise-induced increases
      in blood flow, possibly mediated by the endothelin pathway, preventing an optimal
      stimulus for vascular adaptation. We examined the impact of endothelin receptor
      blockade (bosentan) on exercise-induced blood flow in the brachial artery and on
      pre- and postexercise endothelial function in type 2 diabetes patients (n = 9, 60
      +/- 7 years old) and control subjects (n = 10, 60 +/- 5 years old). Subjects
      reported twice to the laboratory to perform hand-grip exercise in the presence of
      endothelin receptor blockade or placebo. We examined brachial artery endothelial
      function (via flow-mediated dilatation) before and after exercise, as well as
      blood flow during exercise. Endothelin receptor blockade resulted in a larger
      increase in blood flow during exercise in type 2 diabetes patients (P = 0.046),
      but not in control subjects (P = 0.309). Exercise increased shear rate across the
      exercise protocol, unaffected by endothelin receptor blockade. Exercise did not
      alter brachial artery diameter in either group, but endothelin receptor blockade
      resulted in a larger brachial artery diameter in type 2 diabetes patients (P =
      0.033). Exercise significantly increased brachial artery flow-mediated dilatation
      in both groups, unaffected by endothelin receptor blockade. Endothelin receptor
      blockade increased exercise-induced brachial artery blood flow in type 2 diabetes
      patients, but not in control subjects. Despite this effect of endothelin receptor
      blockade on blood flow, we found no impact on baseline or post-exercise
      endothelial function in type 2 diabetes patients or control subjects, possibly
      related to normalization of the shear stimulus during exercise. The successful
      increase in blood flow during exercise in type 2 diabetes patients through
      endothelin receptor blockade may have beneficial effects in repeated exercise
      training. 

PMID- 24928954
TI  - Extracellular acidosis contracts coronary but neither renal nor mesenteric artery
      via modulation of H+,K+-ATPase, voltage-gated K+ channels and L-type Ca2+
      channels.
AB  - Extracellular acidosis (EA) jeopardizes the heart, whereas mild extracellular
      alkalinization is cardioprotective, but it remains elusive how the coronary
      artery (CA) responses to EA. In the present study, EA was demonstrated to induce
      contraction in rat coronary artery (RCA) in a manner dependent on extracellular
      pH (pHo, 7.2-6.6), whereas it did not affect the resting tone of either rat renal
      interlobe artery (RIA) or mesenteric artery (MA). The amplitude of contraction
      provoked by pHo 6.8 was approximately equal to that induced by 60 mmol l(-1) KCl
      at pHo 7.4. Blockade of L-type voltage-gated Ca(2+) channels and inhibition of
      H(+),K(+)-ATPase attenuated the contraction, whereas inhibition of nitric oxide
      synthesis and endothelial denudation augmented it. A molecular probe study showed
      that EA acidified the cytosol of arterial smooth muscle cells (ASMCs) in RIA and
      MA, but alkalinized it in RCA. Extracellular acidosis elevated the intracellular
      Ca(2+) concentration exclusively in RCA ASMCs. Patch-clamp studies showed that EA
      enhanced L-type voltage-gated Ca(2+) channel currents in RCA ASMCs, but depressed
      the currents in MA ASMCs and did not affect the currents in RIA ASMCs.
      Extracellular acidosis depressed voltage-gated K(+) channel (KV) currents only in
      RCA ASMCs. Lansoprazole blunted all these observed effects of EA on RCA. Taken
      together, the present results demonstrate that the responses of RCA to EA are
      different from those of RIA and MA and suggest that activation of L-type voltage
      gated Ca(2+) channels and H(+),K(+)-ATPase as well as depression of KV may, at
      least partly, underlie the EA-induced contraction in RCA. 

PMID- 24928955
TI  - Tonic arterial chemoreceptor activity contributes to cardiac sympathetic
      activation in mild ovine heart failure.
AB  - Heart failure (HF) is associated with a large increase in cardiac sympathetic
      nerve activity (CSNA), which has detrimental effects on the heart and promotes
      arrhythmias and sudden death. There is increasing evidence that arterial
      chemoreceptor activation plays an important role in stimulating renal sympathetic
      nerve activity (RSNA) and muscle sympathetic nerve activity in HF. Given that
      sympathetic nerve activity to individual organs is differentially controlled, we
      investigated whether tonic arterial chemoreceptor activation contributes to the
      increased CSNA in HF. We recorded CSNA and RSNA in conscious normal sheep and in
      sheep with mild HF induced by rapid ventricular pacing (ejection fraction <40%).
      Tonic arterial chemoreceptor function was evaluated by supplementing room air
      with 100% intranasal oxygen (2-3 l min(-1)) for 20 min, thereby deactivating
      chemoreceptors. The effects of hyperoxia on resting levels and baroreflex control
      of heart rate, CSNA and RSNA were determined. In HF, chemoreceptor deactivation
      induced by hyperoxia significantly reduced CSNA [90 +/- 2 versus 75 +/- 5 bursts
      (100 heart beats)(-1), P < 0.05, n = 10; room air versus hyperoxia] and heart
      rate (96 +/- 4 versus 85 +/- 4 beats min(-1), P < 0.001, n = 12). There was no
      change in RSNA burst incidence [93 +/- 4 versus 92 +/- 4 bursts (100 heart
      beats)(-1), n = 7], although due to the bradycardia the RSNA burst frequency was
      decreased (90 +/- 8 versus 77 +/- 7 bursts min(-1), P < 0.001). In normal sheep,
      chemoreceptor deactivation reduced heart rate without a significant effect on
      CSNA or RSNA. In summary, deactivation of peripheral chemoreceptors during HF
      reduced the elevated levels of CSNA, indicating that tonic arterial chemoreceptor
      activation plays a critical role in stimulating the elevated CSNA in HF.

PMID- 24928957
TI  - Faster cross-bridge detachment and increased tension cost in human hypertrophic
      cardiomyopathy with the R403Q MYH7 mutation.
AB  - The first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q
      mutation in the gene encoding beta-myosin heavy chain (beta-MyHC). R403Q locates
      in the globular head of myosin (S1), responsible for interaction with actin, and
      thus motor function of myosin. Increased cross-bridge relaxation kinetics caused
      by the R403Q mutation might underlie increased energetic cost of tension
      generation; however, direct evidence is absent. Here we studied to what extent
      cross-bridge kinetics and energetics are related in single cardiac myofibrils and
      multicellular cardiac muscle strips of three HCM patients with the R403Q mutation
      and nine sarcomere mutation-negative HCM patients (HCMsmn). Expression of R403Q
      was on average 41 +/- 4% of total MYH7 mRNA. Cross-bridge slow relaxation
      kinetics in single R403Q myofibrils was significantly higher (P < 0.0001) than in
      HCMsmn myofibrils (0.47 +/- 0.02 and 0.30 +/- 0.02 s(-1), respectively).
      Moreover, compared to HCMsmn, tension cost was significantly higher in the muscle
      strips of the three R403Q patients (2.93 +/- 0.25 and 1.78 +/- 0.10 MUmol l(-1)
      s(-1) kN(-1) m(-2), respectively) which showed a positive linear correlation with
      relaxation kinetics in the corresponding myofibril preparations. This correlation
      suggests that faster cross-bridge relaxation kinetics results in an increase in
      energetic cost of tension generation in human HCM with the R403Q mutation
      compared to HCMsmn. Therefore, increased tension cost might contribute to HCM
      disease in patients carrying the R403Q mutation. 

PMID- 24928956
TI  - Spatial effects of shifting prisms on properties of posterior parietal cortex
      neurons.
AB  - The posterior parietal cortex contains neurons that respond to visual stimulation
      and motor behaviour. The objective of the current study was to test short-term
      adaptation in neurons in macaque area 7a and the dorsal prelunate during visually
      guided reaching using Fresnel prisms that displaced the visual field. The visual
      perturbation shifted the eye position and created a mismatch between perceived
      and actual reach location. Two non-human primates were trained to reach to visual
      targets before, during and after prism exposure while fixating the reach target
      in different locations. They were required to reach to the physical location of
      the reach target and not the perceived, displaced location. While behavioural
      adaptation to the prisms occurred within a few trials, the majority of neurons
      responded to the distortion either with substantial changes in spatial eye
      position tuning or changes in overall firing rate. These changes persisted even
      after prism removal. The spatial changes were not correlated with the direction
      of induced prism shift. The transformation of gain fields between conditions was
      estimated by calculating the translation and rotation in Euler angles. Rotations
      and translations of the horizontal and vertical spatial components occurred in a
      systematic manner for the population of neurons suggesting that the posterior
      parietal cortex retains a constant representation of the visual field remapping
      between experimental conditions. 

PMID- 24928958
TI  - Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+
      currents.
AB  - Intracellular signalling cascades triggered by oxidative injury can lead to
      upregulation of Kv2.1 K(+) channels at the plasma membrane of dying neurons.
      Membrane incorporation of new channels is necessary for enhanced K(+) efflux and
      a consequent reduction of intracellular K(+) that facilitates apoptosis. We
      showed previously that the observed increase in K(+) currents is a soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated
      process, and that the SNARE protein syntaxin binds directly to Kv2.1 channels. In
      the present study, we tested whether disrupting the interaction of Kv2.1 and
      syntaxin promoted the survival of cortical neurons following injury. Syntaxin is
      known to bind to Kv2.1 in a domain comprising amino acids 411-522 of the
      channel's cytoplasmic C terminus (C1a). Here we show that this domain is required
      for the apoptotic K(+) current enhancement. Moreover, expression of an isolated,
      Kv2.1-derived C1a peptide is sufficient to suppress the injury-induced increase
      in currents by interfering with Kv2.1/syntaxin binding. By subdividing the C1a
      peptide, we were able to localize the syntaxin binding site on Kv2.1 to the most
      plasma membrane-distal residues of C1a. Importantly, expression of this peptide
      segment in neurons prevented the apoptotic K(+) current enhancement and cell
      death following an oxidative insult, without greatly impairing baseline K(+)
      currents or normal electrical profiles of neurons. These results establish that
      binding of syntaxin to Kv2.1 is crucial for the manifestation of oxidant-induced
      apoptosis, and thereby reveal a potential new direction for therapeutic
      intervention in the treatment of neurodegenerative disorders. 

PMID- 24928959
TI  - Neurohormonal signalling in the gastrointestinal tract: new frontiers.

PMID- 24928963
TI  - Opposite regulation of Myc and p21waf1 transcription by STAT3 proteins.

PMID- 24928984
TI  - The Aux/IAA gene rum1 involved in seminal and lateral root formation controls
      vascular patterning in maize (Zea mays L.) primary roots.
AB  - The maize (Zea mays L.) Aux/IAA protein RUM1 (ROOTLESS WITH UNDETECTABLE
      MERISTEMS 1) controls seminal and lateral root initiation. To identify RUM1
      dependent gene expression patterns, RNA-Seq of the differentiation zone of
      primary roots of rum1 mutants and the wild type was performed in four biological
      replicates. In total, 2 801 high-confidence maize genes displayed differential
      gene expression with Fc >=2 and FDR <=1%. The auxin signalling-related genes
      rum1, like-auxin1 (lax1), lax2, (nam ataf cuc 1 nac1), the plethora genes plt1
      (plethora 1), bbm1 (baby boom 1), and hscf1 (heat shock complementing factor 1)
      and the auxin response factors arf8 and arf37 were down-regulated in the mutant
      rum1. All of these genes except nac1 were auxin-inducible. The maize arf8 and
      arf37 genes are orthologues of Arabidopsis MP/ARF5 (MONOPTEROS/ARF5), which
      controls the differentiation of vascular cells. Histological analyses of mutant
      rum1 roots revealed defects in xylem organization and the differentiation of pith
      cells around the xylem. Moreover, histochemical staining of enlarged pith cells
      surrounding late metaxylem elements demonstrated that their thickened cell walls
      displayed excessive lignin deposition. In line with this phenotype, rum1
      dependent mis-expression of several lignin biosynthesis genes was observed. In
      summary, RNA-Seq of RUM1-dependent gene expression in maize primary roots, in
      combination with histological and histochemical analyses, revealed the specific
      regulation of auxin signal transduction components by RUM1 and novel functions of
      RUM1 in vascular development. 

PMID- 24928985
TI  - Zn2+ -induced changes at the root level account for the increased tolerance of
      acclimated tobacco plants.
AB  - Evidence suggests that heavy-metal tolerance can be induced in plants following
      pre-treatment with non-toxic metal concentrations, but the results are still
      controversial. In the present study, tobacco plants were exposed to increasing
      Zn2+ concentrations (up to 250 and/or 500 MUM ZnSO4) with or without a 1-week
      acclimation period with 30 MUM ZnSO4. Elevated Zn2+ was highly toxic for plants,
      and after 3 weeks of treatments there was a marked (>=50%) decline in plant
      growth in non-acclimated plants. Plant acclimation, on the other hand, increased
      plant dry mass and leaf area up to 1.6-fold compared with non-acclimated ones. In
      non-acclimated plants, the addition of 250 MUM ZnSO4 led to transient membrane
      depolarization and stomatal closure within 24h from the addition of the stress;
      by contrast, the acclimation process was associated with an improved stomatal
      regulation and a superior ability to maintain a negative root membrane potential,
      with values on average 37% more negative compared with non-acclimated plants. The
      different response at the plasma-membrane level between acclimated and non
      acclimated plants was associated with an enhanced vacuolar Zn2+ sequestration and
      up to 2-fold higher expression of the tobacco orthologue of the Arabidopsis
      thaliana MTP1 gene. Thus, the acclimation process elicited specific
      detoxification mechanisms in roots that enhanced Zn2+ compartmentalization in
      vacuoles, thereby improving root membrane functionality and stomatal regulation
      in leaves following elevated Zn2+ stress.

PMID- 24928986
TI  - Acute and chronic B cell depletion disrupts CD4+ and CD8+ T cell homeostasis and
      expansion during acute viral infection in mice.
AB  - B cells provide humoral protection against pathogens and promote cellular
      immunity through diverse nonclassical effector functions. To assess B cell
      function in promoting T cell homeostasis, mature B cells were either acutely or
      chronically depleted in mice using CD20 mAb. Acute B cell depletion in either 2-
      or 4-mo-old mice significantly reduced spleen and lymph node CD4(+) and CD8(+) T
      cell numbers, including naive, activated, and Foxp3(+)CD25(+)CD4(+) regulatory T
      cell subsets. The numbers of IFN-gamma- and TNF-alpha-producing T cells were also
      significantly reduced. Chronic B cell depletion for 6 mo in aged naive mice
      resulted in a 40-70% reduction in activated CD4(+) and CD8(+) T cell numbers and
      20-50% reductions in IFN-gamma-producing T cells. Therefore, B cells were
      necessary for maintaining naive CD4(+) and CD8(+) T cell homeostasis for
      subsequent optimal T cell expansion in young and old mice. To determine the
      significance of this finding, a week of B cell depletion in 4-mo-old mice was
      followed by acute viral infection with lymphocytic choriomeningitis virus
      Armstrong. Despite their expansion, activated and cytokine-producing CD4(+) and
      CD8(+) T cell numbers were still significantly reduced 1 wk later. Moreover,
      viral peptide-specific CD4(+) and CD8(+) T cell numbers and effector cell
      development were significantly reduced in mice lacking B cells, whereas
      lymphocytic choriomeningitis virus titers were dramatically increased. Thus, T
      cell function is maintained in B cell-depleted mice, but B cells are required for
      optimal CD4(+) and CD8(+) T cell homeostasis, activation, and effector
      development in vivo, particularly during responses to acute viral infection. 

PMID- 24928987
TI  - Site-specific chemokine expression regulates central nervous system inflammation
      and determines clinical phenotype in autoimmune encephalomyelitis.
AB  - The adoptive transfer of myelin-reactive T cells into wild-type hosts results in
      spinal cord inflammation and ascending paralysis, referred to as conventional
      experimental autoimmune encephalomyelitis (EAE), as opposed to brainstem
      inflammation and ataxia, which characterize disease in IFN-gammaRKO hosts
      (atypical EAE). In this article, we show that atypical EAE correlates with
      preferential upregulation of CXCL2 in the brainstem, and is driven by CXCR2
      dependent recruitment of neutrophils. In contrast, conventional EAE is associated
      with upregulation of CCL2 in the spinal cord, and is driven by recruitment of
      monocytes via a partially CCR2-dependent pathway. This study illustrates how
      regional differences in chemokine expression within a target organ shape the
      spatial pattern and composition of autoimmune infiltrates, leading to disparate
      clinical outcomes. 

PMID- 24928988
TI  - Ficolin-2 inhibits hepatitis C virus infection, whereas apolipoprotein E3
      mediates viral immune escape.
AB  - Human ficolin-2 (L-ficolin/p35) is a lectin-complement pathway activator that is
      present in normal human plasma and is associated with infectious diseases;
      however, little is known regarding the roles and mechanisms of ficolin-2 during
      chronic hepatitis C virus (HCV) infection. In this study, we found that ficolin-2
      inhibits the entry of HCV at an early stage of viral infection, regardless of the
      viral genotype. Ficolin-2 neutralized and inhibited the initial attachment and
      infection of HCV by binding to the HCV envelope surface glycoproteins E1 and E2,
      blocking HCV attachment to low-density lipoprotein receptor (LDLR) and scavenger
      receptor B1, and weakly interfering with CD81 receptor attachment. However, no
      interference with claudin-1 and occludin receptor attachment was observed. The C
      terminal fibrinogen domain (201-313 aa) of ficolin-2 was identified as the
      critical binding region for the HCV-E1-E2 N-glycans, playing a critical role in
      the anti-HCV activity. More importantly, we found that apolipoprotein E (ApoE)3,
      which is enriched in the low-density fractions of HCV RNA-containing particles,
      promotes HCV infection and inhibits ficolin-2-mediated antiviral activity. ApoE3,
      but not ApoE2 and ApoE4, blocked the interaction between ficolin-2 and HCV-E2.
      Our data suggest that the HCV entry inhibitor ficolin-2 is a novel and promising
      antiviral innate immune molecule, whereas ApoE3 blocks the effect of ficolin-2
      and mediates an immune escape mechanism during chronic HCV infection. HCV may be
      neutralized using compounds directed against the lipoprotein moiety of the viral
      particle, and ApoE3 may be a new target to combat HCV infection. 

PMID- 24928989
TI  - CD40 ligand preferentially modulates immune response and enhances protection
      against influenza virus.
AB  - CD40L, a key regulator of the immune system, was studied as both a targeting
      ligand and a molecular adjuvant in nucleoprotein (NP)-based host defense against
      influenza in mouse models with different genetic backgrounds. Adenoviral vectors
      secreting NP-CD40L fusion protein (denoted as rAd-SNP40L) afforded full
      protection of immunocompetent and immunocompromised mice (CD40L(-/-) and CD4(-/
      )) against lethal influenza infection. Mechanistically, rAd-SNP40L preferentially
      induced early and persistent B cell germinal center formation, and accelerated Ig
      isotype-switching and Th1-skewed, NP-specific Ab response. Moreover, it
      drastically augmented primary and memory NP-specific CTL activity and
      polyfunctional CD8(+) T cells. The markedly enhanced nonneutralizing Abs and CTLs
      significantly reduced viral burdens in the lungs of mice upon lethal virus
      challenge. Data generated from CD40L(-/-) and CD4(-/-) mice revealed that the
      protection was indeed CD40L mediated but CD4(+) T cell independent, demonstrating
      the viability of the fusion Ags in protecting immunodeficient hosts. Notably, a
      single dose of rAd-SNP40L completely protected mice from lethal viral challenge 4
      mo after immunization, representing the first report, to our knowledge, on NP in
      conjunction with a molecular adjuvant inducing a robust and long-lasting memory
      immune response against influenza. This platform is characterized by an increased
      in vivo load of CD40-targeted Ag upon the secretion of the fusion protein from
      adenovirus-infected cells and may represent a promising strategy to enhance the
      breadth, durability, and potency of Ag-specific immune responses. 

PMID- 24928990
TI  - Real-time detection of CTL function reveals distinct patterns of caspase
      activation mediated by Fas versus granzyme B.
AB  - Activation of caspase-mediated apoptosis is reported to be a hallmark of both
      granzyme B- and Fas-mediated pathways of killing by CTLs; however, the kinetics
      of caspase activation remain undefined owing to an inability to monitor target
      cell-specific apoptosis in real time. We have overcome this limitation by
      developing a novel biosensor assay that detects continuous, protease-specific
      activity in target cells. Biosensors were engineered from a circularly permuted
      luciferase, linked internally by either caspase 3/7 or granzyme B/caspase 8
      cleavage sites, thus allowing activation upon proteolytic cleavage by the
      respective proteases. Coincubation of murine CTLs with target cells expressing
      either type of biosensor led to a robust luminescent signal within minutes of
      cell contact. The signal was modulated by the strength of TCR signaling, the
      ratio of CTL/target cells, and the type of biosensor used. Additionally, the
      luciferase signal at 30 min correlated with target cell death, as measured by a
      (51)Cr-release assay. The rate of caspase 3/7 biosensor activation was
      unexpectedly rapid following granzyme B- compared with Fas-mediated signal
      induction in murine CTLs; the latter appeared gradually after a 90-min delay in
      perforin- or granzyme B-deficient CTLs. Remarkably, the Fas-dependent, caspase
      3/7 biosensor signal induced by perforin-deficient human CTLs was also detectable
      after a 90-min delay when measured by redirected killing. Thus, we have used a
      novel, real-time assay to demonstrate the distinct pattern of caspase activation
      induced by granzyme B versus Fas in human and murine CTLs. 

PMID- 24928991
TI  - B cells regulate CD4+ T cell responses to papain following B cell receptor
      independent papain uptake.
AB  - Papain, a cysteine protease allergen with inherent adjuvant activity, induces
      potent IL-4 expression by T cells in the popliteal lymph nodes of mice following
      footpad immunization. In this study, we identify a novel, non-BCR-mediated
      capacity for B cells to rapidly bind and internalize papain. B cells subsequently
      regulate the adaptive immune response by enhancing ICOS expression on CD4(+) T
      cells and amplifying Th2 and follicular helper T cell induction. Ab blockade of
      ICOS ligand, expressed by popliteal lymph node B cells, but not dendritic cells,
      at the peak of the response inhibits IL-4 responses in wild-type mice but not B
      cell-deficient mice. Thus, B cells play a critical role in amplifying adjuvant
      dependent Th2 polarization following noncanonical acquisition and internalization
      of the cysteine protease papain. 

PMID- 24928995
TI  - High proportion of CD5+ B cells in infants predicts development of allergic
      disease.
AB  - Delayed maturation of the immune system has been proposed to be a risk factor for
      development of allergy, but B cell maturation in relation to allergic disease has
      not been examined. B cells lose CD5 and acquire CD27 during maturation from
      immature via mature/naive to Ig-secreting cells and memory cells. We sought to
      investigate B cell maturation in relation to development of allergic disease and
      sensitization in the FARMFLORA birth cohort including 65 Swedish children. Total
      B cell numbers, proportions of CD5(+) and CD27(+) B cells, and levels of IgM,
      IgG, IgA, and IgE were measured in blood on repeated occasions from birth to 36
      mo of age, and related to allergic disease and sensitization at 18 and 36 mo of
      age with multivariate discriminant analysis. We also compared the expression of
      CD24 and CD38 within CD5(+) and CD5(neg) B cells in children and in adults. We
      found that infants with a high proportion of CD5(+) B cells at birth and at 1 mo
      of age had an increased risk for having allergic disease at 18 and 36 mo of life.
      Further, the proportions of CD5(+) B cells at 1 mo of age were inversely
      correlated with total IgG levels at 18 and 36 mo of age. The majority of the
      CD5(+) B cells were of a CD24(hi/+)CD38(hi/+) immature/naive phenotype at birth
      (97%), 7 y of age (95%), and in adults (86%). These results suggest that
      development of allergic disease is preceded by an immaturity in neonatal B cell
      phenotype. 

PMID- 24928992
TI  - Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage
      phenotype in pulmonary hypertension.
AB  - Macrophage accumulation is not only a characteristic hallmark but is also a
      critical component of pulmonary artery remodeling associated with pulmonary
      hypertension (PH). However, the cellular and molecular mechanisms that drive
      vascular macrophage activation and their functional phenotype remain poorly
      defined. Using multiple levels of in vivo (bovine and rat models of hypoxia
      induced PH, together with human tissue samples) and in vitro (primary mouse, rat,
      and bovine macrophages, human monocytes, and primary human and bovine
      fibroblasts) approaches, we observed that adventitial fibroblasts derived from
      hypertensive pulmonary arteries (bovine and human) regulate macrophage
      activation. These fibroblasts activate macrophages through paracrine IL-6 and
      STAT3, HIF1, and C/EBPbeta signaling to drive expression of genes previously
      implicated in chronic inflammation, tissue remodeling, and PH. This distinct
      fibroblast-activated macrophage phenotype was independent of IL-4/IL-13-STAT6 and
      TLR-MyD88 signaling. We found that genetic STAT3 haplodeficiency in macrophages
      attenuated macrophage activation, complete STAT3 deficiency increased macrophage
      activation through compensatory upregulation of STAT1 signaling, and deficiency
      in C/EBPbeta or HIF1 attenuated fibroblast-driven macrophage activation. These
      findings challenge the current paradigm of IL-4/IL-13-STAT6-mediated alternative
      macrophage activation as the sole driver of vascular remodeling in PH, and
      uncover a cross-talk between adventitial fibroblasts and macrophages in which
      paracrine IL-6-activated STAT3, HIF1alpha, and C/EBPbeta signaling are critical
      for macrophage activation and polarization. Thus, targeting IL-6 signaling in
      macrophages by completely inhibiting C/EBPbeta or HIF1alpha or by partially
      inhibiting STAT3 may hold therapeutic value for treatment of PH and other
      inflammatory conditions characterized by increased IL-6 and absent IL-4/IL-13
      signaling. 

PMID- 24928994
TI  - Innate PLZF+CD4+ alphabeta T cells develop and expand in the absence of Itk.
AB  - T cell development in the thymus produces multiple lineages of cells, including
      innate T cells. Studies in mice harboring alterations in TCR signaling proteins
      or transcriptional regulators have revealed an expanded population of CD4(+)
      innate T cells in the thymus that produce IL-4 and express the transcription
      factor promyelocytic leukemia zinc finger (PLZF). In these mice, IL-4 produced by
      the CD4(+)PLZF(+) T cell population leads to the conversion of conventional
      CD8(+) thymocytes into innate CD8(+) T cells resembling memory T cells expressing
      eomesodermin. The expression of PLZF, the signature invariant NKT cell
      transcription factor, in these innate CD4(+) T cells suggests that they might be
      a subset of alphabeta or gammadelta TCR(+) NKT cells or mucosal-associated
      invariant T (MAIT) cells. To address these possibilities, we characterized the
      CD4(+)PLZF(+) innate T cells in itk(-/-) mice. We show that itk(-/-) innate
      PLZF(+)CD4(+) T cells are not CD1d-dependent NKT cells, MR1-dependent MAIT cells,
      or gammadelta T cells. Furthermore, although the itk(-/-) innate PLZF(+)CD4(+) T
      cells express alphabeta TCRs, neither beta2-microglobulin-dependent MHC class I
      nor any MHC class II molecules are required for their development. In contrast to
      invariant NKT cells and MAIT cells, this population has a highly diverse TCRalpha
      chain repertoire. Analysis of peripheral tissues indicates that itk(-/-) innate
      PLZF(+)CD4(+) T cells preferentially home to spleen and mesenteric lymph nodes
      owing to increased expression of gut-homing receptors, and that their expansion
      is regulated by commensal gut flora. These data support the conclusion that itk(
      /-) innate PLZF(+)CD4(+) T cells are a novel subset of innate T cells.

PMID- 24928993
TI  - Investigation of soluble and transmembrane CTLA-4 isoforms in serum and
      microvesicles.
AB  - Expression of the CTLA-4 gene is absolutely required for immune homeostasis, but
      aspects of its molecular nature remain undefined. In particular, the
      characterization of the soluble CTLA-4 (sCTLA-4) protein isoform generated by an
      alternatively spliced mRNA of CTLA4 lacking transmembrane-encoding exon 3 has
      been hindered by the difficulty in distinguishing it from the transmembrane
      isoform of CTLA-4, Tm-CTLA-4. In the current study, sCTLA-4 has been analyzed
      using novel mAbs and polyclonal Abs specific for its unique C-terminal amino acid
      sequence. We demonstrate that the sCTLA-4 protein is secreted at low levels
      following the activation of primary human CD4(+) T cells and is increased only
      rarely in the serum of autoimmune patients. Unexpectedly, during our studies
      aimed to define the kinetics of sCTLA-4 produced by activated human CD4(+) T
      cells, we discovered that Tm-CTLA-4 is associated with microvesicles produced by
      the activated cells. The functional roles of sCTLA-4 and microvesicle-associated
      Tm-CTLA-4 warrant further investigation, especially as they relate to the
      multiple mechanisms of action described for the more commonly studied cell
      associated Tm-CTLA-4. 

PMID- 24928996
TI  - Macrophage migration inhibitory factor promotes clearance of pneumococcal
      colonization.
AB  - Human genetic polymorphisms associated with decreased expression of macrophage
      migration inhibitory factor (MIF) have been linked to the risk of community
      acquired pneumonia. Because Streptococcus pneumoniae is the leading cause of
      community-acquired pneumonia and nasal carriage is a precursor to invasive
      disease, we explored the role of MIF in the clearance of pneumococcal
      colonization in a mouse model. MIF-deficient mice (Mif(-/-)) showed prolonged
      colonization with both avirulent (23F) and virulent (6A) pneumococcal serotypes
      compared with wild-type animals. Pneumococcal carriage led to both local
      upregulation of MIF expression and systemic increase of the cytokine. Delayed
      clearance in the Mif(-/-) mice was correlated with reduced numbers of macrophages
      in upper respiratory tract lavages as well as impaired upregulation of MCP
      1/CCL2. We found that primary human monocyte-derived macrophages as well as THP-1
      macrophages produced MIF upon pneumococcal infection in a pneumolysin-dependent
      manner. Pneumolysin-induced MIF production required its pore-forming activity and
      phosphorylation of p38-MAPK in macrophages, with sustained p38-MAPK
      phosphorylation abrogated in the setting of MIF deficiency. Challenge with
      pneumolysin-deficient bacteria demonstrated reduced MIF upregulation, decreased
      numbers of macrophages in the nasopharynx, and less effective clearance. Mif(-/-)
      mice also showed reduced Ab response to pneumococcal colonization and impaired
      ability to clear secondary carriage. Finally, local administration of MIF was
      able to restore bacterial clearance and macrophage accumulation in Mif(-/-) mice.
      Our work suggests that MIF is important for innate and adaptive immunity to
      pneumococcal colonization and could be a contributing factor in genetic
      differences in pneumococcal disease susceptibility. 

PMID- 24928997
TI  - Rituximab efficiently depletes increased CD20-expressing T cells in multiple
      sclerosis patients.
AB  - In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20
      Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease
      activity. Based on indirect evidence, it is generally believed that elimination
      of the Ag-presenting capabilities and Ag nonspecific immune functions of B cells
      underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T
      cells) was shown to also express CD20, but controversy prevails surrounding the
      true existence of this T cell subpopulation. Using single-cell imaging flow
      cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally
      demonstrate the existence of CD3(+)CD20(dim) T cells. We show that in MS
      patients, increased levels of CD3(+)CD20(dim) T cells are effectively depleted by
      RTX. The pathological relevance of this T cell subset in MS remains to be
      determined. However, given their potential proinflammatory functionality,
      depletion of CD20-expressing T cells may also contribute to the therapeutic
      effect of RTX and other mAbs targeting CD20. 

PMID- 24928998
TI  - ERAP1-ERAP2 dimerization increases peptide-trimming efficiency.
AB  - The endoplasmic reticulum aminopeptidases (ERAP)1 and ERAP2 play a critical role
      in the production of final epitopes presented by MHC class I molecules. Formation
      of heterodimers by ERAP1 and ERAP2 has been proposed to facilitate trimming of
      epitope precursor peptides, but the effects of dimerization on ERAP function
      remain unknown. In this study, we produced stabilized ERAP1-ERAP2 heterodimers
      and found that they produced several mature epitopes more efficiently than a mix
      of the two enzymes unable to dimerize. Physical interaction with ERAP2 changes
      basic enzymatic parameters of ERAP1 and improves its substrate-binding affinity.
      Thus, by bringing the two enzymes in proximity and by producing allosteric
      effects on ERAP1, dimerization of ERAP1/2 creates complexes with superior peptide
      trimming efficacy. Such complexes are likely to enhance Ag presentation by cells
      displaying coordinated expression of the two enzymes. 

PMID- 24928999
TI  - Targeting of TLRs inhibits CD4+ regulatory T cell function and activates
      lymphocytes in human peripheral blood mononuclear cells.
AB  - Accumulating evidence suggests elements within tumors induce exhaustion of
      effector T cells and infiltration of immunosuppressive regulatory T cells
      (Tregs), thus preventing the development of durable antitumor immunity.
      Therefore, the discovery of agents that simultaneously block Treg suppressive
      function and reinvigorate effector function of lymphocytes is key to the
      development of effective cancer immunotherapy. Previous studies have shown that
      TLR ligands (TLRLs) could modulate the function of these T cell targets; however,
      those studies relied on cell-free or accessory cell-based assay systems that do
      not accurately reflect in vivo responses. In contrast, we used a human PBMC-based
      proliferation assay system to simultaneously monitor the effect of TLRLs on T
      cells (CD4(+), CD8(+), Tregs), B cells, and NK cells, which gave different and
      even conflicting results. We found that the TLR7/8L:CL097 could simultaneously
      activate CD8(+) T cells, B cells, and NK cells plus block Treg suppression of T
      cells and B cells. The TLRLs TLR1/2L:Pam3CSK4, TLR5L:flagellin, TLR4L:LPS, and
      TLR8/7L:CL075 also blocked Treg suppression of CD4(+) or CD8(+) T cell
      proliferation, but not B cell proliferation. Besides CL097, TLR2L:PGN, CL075, and
      TLR9L:CpG-A, CpG-B, and CpG-C) were strong activators of NK cells. Importantly,
      we found that Pam3CSK4 could: 1) activate CD4(+) T cell proliferation, 2) inhibit
      the expansion of IL-10(+) naturally occurring FOXP3(+) Tregs and induction of IL
      10(+) CD4(+) Tregs (IL-10-producing type 1 Treg), and 3) block naturally
      occurring FOXP3(+) Tregs suppressive function. Our results suggest these agents
      could serve as adjuvants to enhance the efficacy of current immunotherapeutic
      strategies in cancer patients.

PMID- 24929001
TI  - Opposing roles of prostaglandin D2 receptors in ulcerative colitis.
AB  - Proresolution functions were reported for PGD2 in colitis, but the role of its
      two receptors, D-type prostanoid (DP) and, in particular, chemoattractant
      receptor homologous molecule expressed on Th2 cells (CRTH2), is less well
      defined. We investigated DP and CRTH2 expression and function during human and
      murine ulcerative colitis (UC). Expression of receptors was measured by flow
      cytometry on peripheral blood leukocytes and by immunohistochemistry and
      immunoblotting in colon biopsies of patients with active UC and healthy
      individuals. Receptor involvement in UC was evaluated in a mouse model of dextran
      sulfate sodium colitis. DP and CRTH2 expression changed in leukocytes of patients
      with active UC in a differential manner. In UC patients, DP showed higher
      expression in neutrophils but lower in monocytes as compared with control
      subjects. In contrast, CRTH2 was decreased in eosinophils, NK, and CD3(+) T cells
      but not in monocytes and CD3(+)/CD4(+) T cells. The decrease of CRTH2 on blood
      eosinophils clearly correlated with disease activity. DP correlated positively
      with disease activity in eosinophils but inversely in neutrophils. CRTH2
      internalized upon treatment with PGD2 and 11-dehydro TXB2 in eosinophils of
      controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in
      the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595
      improved, whereas the DP antagonist MK0524 worsened inflammation in murine
      colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2
      on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue,
      where it may contribute to inflammation, whereas DP most likely promotes anti
      inflammatory actions. 

PMID- 24929000
TI  - A balance between B cell receptor and inhibitory receptor signaling controls
      plasma cell differentiation by maintaining optimal Ets1 levels.
AB  - Signaling through the BCR can drive B cell activation and contribute to B cell
      differentiation into Ab-secreting plasma cells. The positive BCR signal is
      counterbalanced by a number of membrane-localized inhibitory receptors that limit
      B cell activation and plasma cell differentiation. Deficiencies in these negative
      signaling pathways may cause autoantibody generation and autoimmune disease in
      both animal models and human patients. We have previously shown that the
      transcription factor Ets1 can restrain B cell differentiation into plasma cells.
      In this study, we tested the roles of the BCR and inhibitory receptors in
      controlling the expression of Ets1 in mouse B cells. We found that Ets1 is
      downregulated in B cells by BCR or TLR signaling through a pathway dependent on
      PI3K, Btk, IKK2, and JNK. Deficiencies in inhibitory pathways, such as a loss of
      the tyrosine kinase Lyn, the phosphatase Src homology region 2 domain-containing
      phosphatase 1 (SHP1) or membrane receptors CD22 and/or Siglec-G, result in
      enhanced BCR signaling and decreased Ets1 expression. Restoring Ets1 expression
      in Lyn- or SHP1-deficient B cells inhibits their enhanced plasma cell
      differentiation. Our findings indicate that downregulation of Ets1 occurs in
      response to B cell activation via either BCR or TLR signaling, thereby allowing B
      cell differentiation and that the maintenance of Ets1 expression is an important
      function of the inhibitory Lyn -> CD22/SiglecG -> SHP1 pathway in B cells. 

PMID- 24929002
TI  - The Wnt/beta-catenin pathway attenuates experimental allergic airway disease.
AB  - Signaling via the Wnt/beta-catenin pathway plays crucial roles in embryogenesis
      and homeostasis of adult tissues. In the lung, the canonical Wnt/beta-catenin
      pathway has been implicated in remodeling processes, development of emphysema,
      and fibrosis. However, its relevance for the modulation of allergic responses in
      the lung remains unclear. Using genetically modified mice with lung-specific
      inducible (doxycycline) Wnt-1 expression (CCSP-rtTA * tetO-Wnt1), the impact of
      Wnt on the development of allergic airway disease was analyzed. Overexpression of
      Wnt during the allergen challenge phase attenuated the development of airway
      inflammation in an acute model, as well as in a more therapeutic model of
      secondary challenge. These findings were further supported by treatment of
      allergen-sensitized mice with LiCl during challenge. Similar to Wnt, LiCl
      prevented the degradation of beta-catenin and, thus, attenuated allergic airway
      inflammation and hyperresponsiveness. Migration studies revealed that lung
      specific expression of Wnt reduced the migration of Ag-loaded dendritic cells
      (DCs) into the draining lymph nodes following allergen challenge. Administration
      of in vitro allergen-loaded DCs overcame Wnt-mediated suppression of airway
      inflammation. Furthermore, in vitro studies confirmed that DC-dependent T cell
      activation is impaired by blocking beta-catenin degradation. These results
      demonstrate an important role for the canonical Wnt/beta-catenin pathway in the
      DC-mediated regulation of allergic responses in the lung. 

PMID- 24929003
TI  - DOK3 is required for IFN-beta production by enabling TRAF3/TBK1 complex formation
      and IRF3 activation.
AB  - The downstream of kinase (DOK) family of adaptors is generally involved in the
      negative regulation of signaling pathways. DOK1, 2, and 3 were shown to attenuate
      TLR4 signaling by inhibiting Ras-ERK activation. In this study, we elucidated a
      novel role for DOK3 in IFN-beta production. Macrophages lacking DOK3 were
      impaired in IFN-beta synthesis upon influenza virus infection or polyinosinic
      polyribocytidylic acid stimulation. In the absence of DOK3, the transcription
      factor IFN regulatory factor 3 was not phosphorylated and could not translocate
      to the nucleus to activate ifn-beta gene expression. Interestingly, polyinosinic
      polyribocytidylic acid-induced formation of the upstream TNFR-associated factor
      (TRAF) 3/TANK-binding kinase (TBK) 1 complex was compromised in dok3(-/-)
      macrophages. DOK3 was shown to bind TBK1 and was required for its activation.
      Furthermore, we demonstrated that overexpression of DOK3 and TBK1 could
      significantly enhance ifn-beta promoter activity. DOK3 was also shown to bind
      TRAF3, and the binding of TRAF3 and TBK1 to DOK3 required the tyrosine-rich C
      terminal domain of DOK3. We further revealed that DOK3 was phosphorylated by
      Bruton's tyrosine kinase. Hence, DOK3 plays a critical and positive role in TLR3
      signaling by enabling TRAF3/TBK1 complex formation and facilitating TBK1 and IFN
      regulatory factor 3 activation and the induction of IFN-beta production. 

PMID- 24929004
TI  - A high frequency of MDSCs in sepsis patients, with the granulocytic subtype
      dominating in gram-positive cases.
AB  - The causative microorganisms dictate the type of MDSC generated in sepsis
      patients, and a large proportion of PMN-MDSCs in gram-positive sepsis includes
      immunosuppressive myeloid blasts. MDSCs constitute a heterogeneous population of
      immature myeloid cells that potently suppress immune responses. They were
      identified originally in cancer patients and have since been reported to occur
      also in chronic inflammation, autoimmunity, and even bacterial infections. Human
      MDSCs are commonly divided into Mo-MDSCs and granulocytic (PMN-MDSCs) subtypes.
      To what extent the bona fide cancer MDSCs are representative of the proposed
      MDSCs found in other diseases is not well known. PMN-MDSCs have been found
      previously to be enriched among LDGs in density gradient-centrifuged blood. In
      this study, we analyzed potential MDSCs in sepsis patients with different
      causative microorganisms, using total peripheral blood compared with density
      gradient-centrifuged blood. We found a high frequency of typical CD14(+)HLA
      DR(low) Mo-MDSCs in all sepsis patients, whereas the typical PMN-MDSCs, as well
      as a prominent CD14(low) PMN-MDSC-like population, appeared preferentially in
      gram-positive cases. The CD14(low) PMN-MDSC variant was demonstrated to suppress
      T cell proliferation in vitro via a ROS-dependent mechanism, to display an
      increased IL-10:TNF-alpha ratio, and to present with signs of immaturity: blast
      morphology and low cytokine levels. We conclude that a spectrum of cells with
      MDSC features is enriched in sepsis and that the microbial origin of sepsis
      contributes to the substantial interindividual patient variation in the MDSC
      pattern.

PMID- 24929006
TI  - Essential oil composition, antioxidant and antifungal activities of Salvia
      sclarea L. from Munzur Valley in Tunceli, Turkey.
AB  - The essential oil composition and in vitro antioxidant and antifungal activity of
      the Salvia sclarea L. from Munzur Valley in Tunceli, Turkey were evaluated in
      this research. The in vitro antifungal activity of ethanol, hexane and aqueous
      extracts of S. sclarea against pathogen fungi Epicoccum nigrum and Colletotrichum
      coccodes were investigated. The essential oil of aerial parts of S. sclarea was
      obtained by hydrodistillation and was analysed by GC and GC-MS. Total antioxidant
      status was determined by using Rel assay diagnostics TAS assay kit (Lot.RL024) by
      Multiscan FC (Thermo). 33 compounds were identified representing the 85.0% of the
      total oil. The most abundant components (>5%) of the S. sclarea essential oils
      were caryophyllene oxide (24.1%), sclareol (11.5%), spathulenol (11.4%), 1H
      naphtho (2,1,6) pyran (8.6%) and b-caryophyllene (5.1%). The best antifungal and
      antioxidant effect was seen in ethanolic S. sclarea extract. It can be said that
      Salvia sclerae could be used as natural antioxidant.

PMID- 24929005
TI  - N-Octanoyl dopamine transiently inhibits T cell proliferation via G1 cell-cycle
      arrest and inhibition of redox-dependent transcription factors.
AB  - Recently, we developed a nonhemodynamic dopamine derivative, NOD, which has
      profound anti-inflammatory effects in vitro. As NOD also protects rats from
      ischemic AKI, the present study tested whether NOD is able to modulate cellular
      immunity for potential use as a T cell-suppressive agent. To this end, T cells
      were stimulated by anti-CD3/CD28 or PMA/ionomycin in the presence or absence of
      different concentrations of NOD. T cell proliferation, activation markers,
      intracellular cytokine expression, and activation of transcription factors were
      assessed. Whereas T cell proliferation was inhibited significantly by NOD at Day
      3, proliferation was restored at Day 7 or later depending on the NOD
      concentration used. Inhibition of proliferation was reflected by a diminished
      CD25 expression and switch from naive to memory T cells. Early TCR activation
      events were unaffected, yet NF-kappaB and AP-1 were strongly inhibited by NOD.
      The inhibitory effect of NOD seemed to be dependent on its redox activity, as
      NOT, a redox-inactive NOD derivate, did not influence proliferation. NOD
      displayed synergistic effects with CNIs on T cell proliferation. Our data
      demonstrate that NOD displays T cell-suppressive activity. In keeping with its
      anti-inflammatory action and its beneficial effect on ischemia-induced AKI, NOD
      may be an interesting drug candidate to prevent CNI-related side-effects. 

PMID- 24929007
TI  - Human umbilical cord blood cell transplantation improves cardiac function in a
      myoardial infarction rat model but induces intestinal graft versus host disease.
AB  - Human umbilical cord blood cell (HUCBC) has low immunity. In the present study we
      investigated intestinal graft-versus-host disease (GVHD) induced by HUCBC
      transplantation in a myocardial infarction (MI) rat model. MI was established by
      using left anterior descending coronary artery (LAD) ligation. HUCBCs were
      injected into the animals 5 days post MI. Four weeks after the HUCBC
      transplantation, histology changes in small intestine were observed under an
      optical microscope. In addition, cardiac functions were tested. Further, factor
      VIII, vascular endothelial growth factor (VEGF) in the myocardium and small
      intestine were assayed. The HUCBC transplantation significantly induced
      intestinal GVHD in the MI rats. The HUCBC implantation remarkably improved
      ejection fraction (EF), fractional shortening (FS), and dp/dtmax in the MI rats
      (P<0.05). In the myocardium, the capillary density was larger in the small
      intestine of the HUCBC-transplanted rats compared to the controls. Real-time PCR
      and western blotting revealed that VEGF mRNA and protein levels in the myocardium
      and the small intestine dramatically significantly upregulated in the HUCBC
      transplanted rats (P<0.05). The HUCBC transplantation significantly improves
      aggravated cardiac function of MI rats, but it induces intestinal GVHD.

PMID- 24929008
TI  - Functional ability loss in sensory impaired and sensory unimpaired very old
      adults: analyzing causal relations with positive affect across four years.
AB  - This paper focuses on the relationship between functional ability (FA) and
      positive affect (PA), a major component of well-being, in sensory impaired very
      old adults (SI) compared with sensory unimpaired individuals (UI). Previous
      research mostly suggests a robust causal impact of FA on PA. However, some
      research, drawing from Fredrickson's broaden-and-build theory, also points to the
      possibility of an inverse causality between FA and PA. We examine in this paper
      both of these causal directions in SI as well as UI individuals across a 4year
      observation period. Additionally, we checked for the role of negative affect
      (NA). The T1-T2 sample comprised 81 out of 237 SI individuals (visually or
      hearing impaired) assessed at T1, with a mean age at T1 of 81.8years, and 87 UI
      individuals out of 150 assessed at T1, with a mean age at T1 of 81.5years.
      Established scales were used to assess FA, PA, and NA. Using cross-lagged panel
      analysis to examine the direction of causality, our findings indicate that FA has
      significant impact on PA in both the SI and the UI group, whereas the alternative
      causal pathway was not confirmed. Both cross-lagged relationships between FA and
      NA were non-significant. No group differences in path strengths between SI and UI
      were present. Our study provides evidence that FA is a key competence for
      successful emotional aging in vulnerable groups of very old adults such as SI as
      well as in UI adults in advanced old age. 

PMID- 24929009
TI  - Resting energy expenditure (REE) in an old-old population: implications for
      metabolic stress.
AB  - The basis of nutritional therapy and thus an adequate nutrient intake is the
      assessment of energy need. On the other end, the assessment of individual energy
      requirements based on the gold standard, indirect calorimetry, is associated with
      feasibility difficulties in geriatric settings. To identify the most accurate
      predictive equations for resting energy expenditure (REE) in older subjects with
      overweight, 17 predictive equations were compared to indirect calorimetry
      measurement in a study population of 20 obese older subjects (mean BMI 33.7+/
      4.5kg/m(2); mean age 79.8+/-8.1 years; gender 5 males and 15 females) and 20 age
      matched controls with a normal body weight (mean BMI 24.9+/-2.5 kg/m(2); mean age
      82.1+/-6.6 years; gender 9 males and 11 females). The comparison led to two
      significant observations: the predictive equations used led to a much better
      estimation of the REE in the control group than in the obese older subjects. In
      addition, the most accurate equation for estimating the REE in the obese older
      subjects has been shown to be that by Luhrmann et al. Further studies are needed
      to assess the feasibility of using this equation in a routine geriatric setting. 

PMID- 24929010
TI  - Exogenous dehydroisoandrosterone sulfate reverses the dendritic changes of the
      central neurons in aging male rats.
AB  - Sex hormones are known to help maintaining the cognitive ability in male and
      female rats. Hypogonadism results in the reduction of the dendritic spines of
      central neurons which is believed to undermine memory and cognition and cause
      fatigue and poor concentration. In our previous studies, we have reported age
      related regression in dendrite arbors along with loss of dendritic spines in the
      primary somatosensory cortical neurons in female rats. Furthermore, castration
      caused a reduction of dendritic spines in adult male rats. In light of this, it
      was surmised that dendritic structures might change in normal aging male rats
      with advancing age. Recently, dehydroepiandrosterone sulfate (DHEAS) has been
      reported to have memory-enhancing properties in aged rodents. In this study,
      normal aging male rats, with a reduced plasma testosterone level of 75-80%, were
      used to explore the changes in behavioral performance of neuronal dendritic arbor
      and spine density. Aging rats performed poorer in spatial learning memory (Morris
      water maze). Concomitantly, these rats showed regressed dendritic arbors and
      spine loss on the primary somatosensory cortical and hippocampal CA1 pyramidal
      neurons. Exogenous DHEAS and testosterone treatment reversed the behavioral
      deficits and partially restored the spine loss of cortical neurons in aging male
      rats but had no effects on the dendritic arbor shrinkage of the affected neurons.
      It is concluded therefore that DHEAS, has the efficacy as testosterone, and that
      it can exert its effects on the central neuron level to effectively ameliorate
      aging symptoms. 

PMID- 24929011
TI  - Solid self-microemulsifying dispersible tablets of celastrol: formulation
      development, charaterization and bioavailability evaluation.
AB  - The aims of this study were to choose a suitable adsorbent of self-microemulsion
      and to develop a fine solid self-microemulsifying dispersible tablets for
      promoting the dissolution and oral bioavailability of celastrol. Solubility test,
      self-emulsifying grading test, droplet size analysis and ternary phase diagrams
      test were performed to screen and optimize the composition of liquid celastrol
      self-microemulsifying drug delivery system (SMEDDS). Then microcrystalline
      cellulose KG 802 was added as a suitable adsorbent into the optimized liquid
      celastrol-SMEDDS formulation to prepare the dispersible tablets by wet
      granulation compression method. The optimized formulation of celastrol-SMEDDS
      dispersible tablets was finally determinated by the feasibility of the preparing
      process and redispersibility. The in vitro study showed that the dispersible
      tablets could disperse in the dispersion medium within 3 min with the average
      particle size of 25.32 +/- 3.26 nm. In vivo pharmacokinetic experiments of rats,
      the relative bioavailability of celastrol SMEDDS and SMEDDS dispersible tablets
      compared to the 0.4% CMC-Na suspension was 569 +/- 7.07% and 558 +/- 6.77%,
      respectively, while there were no significant difference between the SMEDDS and
      SMEDDS dispersible tablets. The results suggest the potential use of SMEDDS
      dispersible tablets for the oral delivery of poorly water-soluble terpenes drugs,
      such as celastrol.

PMID- 24929012
TI  - Self-assembled drug delivery systems. Part 7: hepatocyte-targeted nanoassemblies
      of an adefovir lipid derivative with cytochrome P450-triggered drug release.
AB  - A novel strategy was used in the design of self-assembled drug delivery systems
      (SADDSs) in this study. The nanoassemblies of an amphiphilic adefovir lipid
      derivative were prepared and demonstrated to have the functions of hepatocyte
      targeting, enzyme-triggered drug release and high anti-hepatitis effect. An
      amphiphilic adefovir lipid derivative, N-lauroyl-1-(3-chlorophenyl)-1,3-propanyl
      phosphonyl adefovir (LCPA) was prepared and formed the nanoassemblies by
      injecting the mixture of LCPA and another amphiphilic polymer, d-galactide
      polyoxyethylene (20) cetyl ether (GPCE) (ca. 20:1, mol/mol) into water. The
      nanoassemblies were very stable and showed negative charge. LCPA was sensitive to
      the cytochrome P450 isozymes that were expressed predominantly in the hepatocytes
      to produce adefovir. GPCE contained a long hydrophilic chain and a galactose
      ligand targeting the asialoglycoprotein receptors overexpressed on the surface of
      hepatocytes. The nanoassemblies showed the long-circulating and liver targeting
      effects according to the results of pharmacokinetics, tissue distribution and
      fluorescence imagination after bolus intravenous administration of the
      nanoassemblies to the mice. The highly efficient hepatitis B treatment was
      achieved by 10 day continuous administration of the nanoassemblies to the HBV
      infected mice. Many functions were combined in the nanoassemblies, including
      prodrug, molecular self-assembly, nanotechnology, long-circulating, hepatocyte
      targeting and hepatocyte over expressing enzyme-triggered drug release.

PMID- 24929013
TI  - A combined bottom-up/top-down approach to prepare a sterile injectable
      nanosuspension.
AB  - To prepare a uniform nanosuspension of strongly hydrophobic riboflavin laurate
      (RFL) allowing sterile filtration, physical modification (bottom-up) was combined
      with high-pressure homogenization (top-down) method. Unlike other bottom-up
      approaches, physical modification with surfactants (TPGS and PL-100) by
      lyophilization controlled crystallization and compensated for the poor
      wettability of RFL. On one hand, crystal growth and aggregation during freezing
      was restricted by a stabilizer-layer adsorbed on the drug surface by hydrophobic
      interaction. On the other hand, subsequent crystallization of drug in the
      sublimation process was limited to the interstitial spaces between solvent
      crystals. After lyophilization, modified drug with a smaller particle size and
      better wettability was obtained. When adding surfactant solution, water molecules
      passed between the hydrophilic groups of surface active molecules and activated
      the polymer chains allowing them to stretch into water. The coarse suspension was
      crushed into a nanosuspension (MP=162 nm) by high-pressure homogenization. For
      long term stability, lyophilization was applied again to solidify the
      nanosuspension (sorbitol as cryoprotectant). A slight crystal growth to about 600
      nm was obtained to allow slow release for a sustained effect after muscular
      administration. Moreover, no paw-licking responses and very slight muscular
      inflammation demonstrated the excellent biocompatibility of this long-acting RFL
      injection.

PMID- 24929014
TI  - Development and characterization of mucoadhesive chitosan films for ophthalmic
      delivery of cyclosporine A.
AB  - Ocular chitosan films were prepared in order to prolong ocular delivery of
      cyclosporine A. The mucoadhesive films were prepared using the solvent casting
      evaporation method. A 2(4) full factorial design was used to evaluate the effect
      of 4 preparation parameters on the film thickness, swelling index and mechanical
      properties. Moreover, uniformity of content and in vitro drug release were
      investigated. Possible interactions between the film excipients were studied by
      FTIR analysis. In vitro experiments were performed in order to evaluate the
      cytotoxicity and anti-inflammatory activity of the chitosan films. Film
      thickness, water uptake, mechanical properties and in vitro release of
      cyclosporine A were dependent on film composition, especially on the amount of
      plasticizer. Lower drug release was measured from chitosan films containing a
      higher amount of plasticizer as glycerol decreased the swelling of chitosan
      films. FTIR spectra suggest a reorganization of hydrogen bonds between chitosan
      chains in the presence of glycerol and cyclodextrins. None of the film
      formulations showed significant cytotoxicity as compared to the negative control
      using human epithelial cells (HaCaT). Cyclosporine A dispersed in the various
      film formulations remained anti-inflammatorily active as significant suppression
      of interleukin-2 secretion in concanavalin A stimulated Jurkat T cells was
      measured.

PMID- 24929015
TI  - Stability of an anti-stroke peptide: driving forces and kinetics in chemical
      degradation.
AB  - NR2B9c (Lys-Leu-Ser-Ser-Ile-Glu-Ser-Asp-Val) is a 9-amino acid peptide that has
      been illustrated to be a potential anti-stroke drug. For more effective
      treatment, suitable drug delivery systems should be developed. However, little is
      known about the stability of NR2B9c which is essential to its formulation. In
      this study, a reversed-phase high-performance liquid chromatography (HPLC) was
      applied to study the forced degradation behavior and stability of NR2B9c. HPLC
      studies were performed with an C8 column using a mobile phase consisting of
      acetonitrile (14.5:85.5, v/v) and aqueous solution (0.1% trifluoroacetic acid
      (TFA) and 0.05 M KH2PO4). The flow rate and the wavelength set during HPLC
      detection were 1.0 mL/min and 205 nm, respectively. The degradation pattern of
      NR2B9c aqueous solution followed pseudo first-order kinetics. The degradation
      rate at pH 7.5 was the slowest according to the plotting V-shaped pH-rate
      profile. The influence of temperature on the rate of reactions was interpreted in
      terms of Arrhenius equation (r(2)>0.98). Thermodynamic parameters were calculated
      based on Eyring equation (r(2)>0.98). The concentrations of drug, buffer species,
      buffer concentrations, oxidation and organic solvents have noticeable effects on
      the degradation of NR2B9c while ultrasound shows little impact under the
      experimental conditions. In a word, this study may give a detailed description of
      stability of NR2B9c.

PMID- 24929017
TI  - Processing by the main olfactory system of chemosignals that facilitate mammalian
      reproduction.
AB  - This article is part of a Special Issue "Chemosignals and Reproduction". Most
      mammalian species possess two parallel circuits that process olfactory
      information. One of these circuits, the accessory system, originates with sensory
      neurons in the vomeronasal organ (VNO). This system has long been known to detect
      non-volatile pheromonal odorants from conspecifics that influence numerous
      aspects of social communication, including sexual attraction and mating as well
      as the release of luteinizing hormone from the pituitary gland. A second circuit,
      the main olfactory system, originates with sensory neurons in the main olfactory
      epithelium (MOE). This system detects a wide range of non-pheromonal odors
      relevant to survival (e.g., food and predator odors). Over the past decade
      evidence has accrued showing that the main olfactory system also detects a range
      of volatile odorants that function as pheromones to facilitate mate recognition
      and activate the hypothalamic-pituitary-gonadal neuroendocrine axis. We review
      early studies as well as the new literature supporting the view that the main
      olfactory system processes a variety of different pheromonal cues that facilitate
      mammalian reproduction. 

PMID- 24929016
TI  - GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during
      development.
AB  - The intestinal epithelium performs vital roles in organ function by absorbing
      nutrients and providing a protective barrier. The zinc-finger containing
      transcription factors GATA4 and GATA6 regulate enterocyte gene expression and
      control regional epithelial cell identity in the adult intestinal epithelium.
      Although GATA4 and GATA6 are expressed in the developing intestine, loss of
      either factor alone during the period of epithelial morphogenesis and
      cytodifferentiation fails to disrupt these processes. Therefore, we tested the
      hypothesis that GATA4 and GATA6 function redundantly to control these aspects of
      intestinal development. We used Villin-Cre, which deletes specifically in the
      intestinal epithelium during the period of villus development and epithelial
      cytodifferentiation, to generate Gata4Gata6 double conditional knockout embryos.
      Mice lacking GATA4 and GATA6 in the intestinal epithelium died within 24h of
      birth. At E18.5, intestinal villus architecture and epithelial cell populations
      were altered. Enterocytes were lost, and goblet cells were increased.
      Proliferation was also increased in GATA4-GATA6 deficient intestinal epithelium.
      Although villus morphology appeared normal at E16.5, the first time at which both
      Gata4 and Gata6 were efficiently reduced, changes in expression of markers of
      enterocytes, goblet cells, and proliferative cells were detected. Moreover,
      goblet cell number was increased at E16.5. Expression of the Notch ligand Dll1
      and the Notch target Olfm4 were reduced in mutant tissue indicating decreased
      Notch signaling. Finally, we found that GATA4 occupies chromatin near the Dll1
      transcription start site suggesting direct regulation of Dll1 by GATA4. We
      demonstrate that GATA4 and GATA6 play an essential role in maintaining proper
      intestinal epithelial structure and in regulating intestinal epithelial
      cytodifferentiation. Our data highlight a novel role for GATA factors in fine
      tuning Notch signaling during intestinal epithelial development to repress goblet
      cell differentiation. 

PMID- 24929019
TI  - Tiny bubbles: coronary aneurysms and lupus.

PMID- 24929018
TI  - A curious cause of cavitations: Nocardia pneumonia.

PMID- 24929020
TI  - Prolonged pyrexia and hepatitis: Q fever.

PMID- 24929021
TI  - Prior history of falls and risk of outcomes in atrial fibrillation: the Loire
      Valley Atrial Fibrillation Project.
AB  - BACKGROUND: Patients with nonvalvular atrial fibrillation are often denied oral
      anticoagulation due to falls risk. The latter is variably defined, and existing
      studies have not compared the associated risk of bleeding with other
      cardiovascular events. There are no data about outcomes in individuals with
      nonvalvular atrial fibrillation with a prior history of (actual) falls, rather
      than being "at risk of falls." Our objective was to evaluate the risk of
      cardiovascular outcomes associated with prior history of falls in patients with
      atrial fibrillation in a contemporary "real world" cohort. METHODS: Patients with
      nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010
      were included. Stroke/thromboembolism event rates were calculated according to
      prior history of falls. Risk factors were investigated by Cox regression.
      RESULTS: Among 7156 atrial fibrillation patients, prior history of falls/trauma
      was uncommon (n = 76; 1.1%). Compared with patients without history of falls,
      those patients were older and less likely to be on oral anticoagulation; they
      also had higher risk scores for stroke/thromboembolism but not for bleeding.
      Compared with no prior history of falls, rates of stroke/thromboembolism (P =
      .01) and all-cause mortality (P < .0001) were significantly higher in patients
      with previous falls. In multivariable analyses, prior history of falls was
      independently associated with stroke/thromboembolism (hazard ratio [HR] 5.19; 95%
      confidence interval [CI], 2.1-12.6; P < .0001), major bleeding (HR 3.32 [1.23
      8.91]; P = .02), and all-cause mortality (HR 3.69; 95% CI, 1.52-8.95; P = .04),
      but not hemorrhagic stroke (HR 4.20; 95% CI, 0.58-30.48; P = .16) in patients on
      oral anticoagulation. CONCLUSION: In this large "real world" atrial fibrillation
      cohort, prior history of falls was uncommon but independently increased risk of
      stroke/thromboembolism, bleeding, and mortality, but not hemorrhagic stroke in
      the presence of anticoagulation. Prior history of (actual) falls may be a more
      clinically useful risk prognosticator than "being at risk of falls."

PMID- 24929022
TI  - Chronic coinfections in patients diagnosed with chronic lyme disease: a
      systematic review.
AB  - PURPOSE: Often, the controversial diagnosis of chronic Lyme disease is given to
      patients with prolonged, medically unexplained physical symptoms. Many such
      patients also are treated for chronic coinfections with Babesia, Anaplasma, or
      Bartonella in the absence of typical presentations, objective clinical findings,
      or laboratory confirmation of active infection. We have undertaken a systematic
      review of the literature to evaluate several aspects of this practice. METHODS:
      Five systematic literature searches were performed using Boolean operators and
      the PubMed search engine. RESULTS: The literature searches did not demonstrate
      convincing evidence of: 1) chronic anaplasmosis infection; 2) treatment
      responsive symptomatic chronic babesiosis in immunocompetent persons in the
      absence of fever, laboratory abnormalities, and detectable parasitemia; 3) either
      geographically widespread or treatment-responsive symptomatic chronic infection
      with Babesia duncani in the absence of fever, laboratory abnormalities, and
      detectable parasitemia; 4) tick-borne transmission of Bartonella species; or 5)
      simultaneous Lyme disease and Bartonella infection. CONCLUSIONS: The medical
      literature does not support the diagnosis of chronic, atypical tick-borne
      coinfections in patients with chronic, nonspecific illnesses.

PMID- 24929023
TI  - Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid
      arthritis: a randomized, double-blind, placebo-controlled pilot study.
AB  - The aim of this study was to demonstrate the safety and efficacy of H2-saline
      infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized,
      double-blind, placebo-controlled investigation of the infusion of 1 ppm H2
      dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to
      receive 500 ml of either H2-saline or placebo-saline, which was drop infused
      intravenously (DIV) daily for 5 days. The disease activity score in 28 joints
      (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks.
      Therapeutic effects of H2-saline on joint inflammation were estimated by
      measuring serum biomarkers for RA, tumor necrosis factor-alpha (TNFalpha),
      interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8
      hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased
      from 5.18 +/- 1.16 to 4.02 +/- 1.25 immediately post infusion and reached 3.74 +/
      1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo
      group throughout the study. IL-6 levels in the H2 group significantly decreased
      in 4 weeks by 37.3 +/- 62.0% compared to baseline, whereas it increased by 33.6
      +/- 34.4% in the placebo group. TNFalpha levels did not change remarkably in the
      H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative
      ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4
      weeks, MMP3 was significantly reduced by 19.2% +/- 24.6% in the H2 group, and
      increased by 16.9% +/- 50.2% in the placebo group. Drop infusion of H2 safely and
      effectively reduced RA disease activity.

PMID- 24929024
TI  - Targeting the genetic alterations of the PI3K-AKT-mTOR pathway: its potential use
      in the treatment of bladder cancers.
AB  - Urothelial carcinoma of the bladder is the most frequent tumor of the urinary
      tract and represents the fifth cause of death by cancer worldwide. The current
      first line chemotherapy is a combination of cisplatin and gemcitabine with median
      survival not exceeding 15months. Vinflunine is the only drug approved by EMEA as
      second-line treatment and few progresses have been made for the past 20years to
      increase the survival of metastatic patients, especially those who are not
      eligible for cisplatin-based regimen. The recent studies characterizing the
      genetic background of urothelial cancers of the bladder, revealed chromosomal
      alterations that are not seen at the same level in other types of cancers. This
      is especially the case for mutations of genes involved in the PI3K/AKT/mTOR
      signaling pathway that occupies a major place in the etiology of these tumors.
      Here, we describe the mutations leading to constitutive activation of the
      PI3K/AKT/mTOR pathway and discuss the potential use of the different classes of
      PI3K/AKT/mTOR inhibitors in the treatment of urothelial bladder cancers. Despite
      the recent pivotal study evidencing specific mutations of TSC1 in bladder cancer
      patients responding to everolimus and the encouraging results obtained with other
      derivatives than rapalogs, few clinical trials are ongoing in bladder cancers.
      Because of the genetic complexity of these tumors, the cross-talks of the
      PI3K/AKT/mTOR pathway with other pathways, and the small number of eligible
      patients, it will be of utmost importance to carefully choose the drugs or drug
      combinations to be further tested in the clinic. 

PMID- 24929025
TI  - Neuropsychological performance, brain imaging, and driving violations in multiple
      sclerosis.
AB  - OBJECTIVE: To examine the relationship between third ventricular width, a measure
      of thalamic brain atrophy, and motor vehicle violation type and frequency in a
      cohort of patients with multiple sclerosis (MS). DESIGN: Retrospective cohort
      study. SETTING: Tertiary care university hospital. PARTICIPANTS: Thirty-five
      individuals with clinically confirmed relapsing-remitting multiple sclerosis and
      35 age-, sex-, and education-matched community-dwelling healthy comparisons
      (N=70). Participants were aged between 25 and 65 years. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Data on motor vehicle violations were obtained
      from an online database (Iowa Courts Online). The violations were categorized as
      follows: (1) speeding, (2) nonmoving safety, (3) administrative, (4) alcohol
      related offense, (5) moving safety, and (6) total violations. Neuropsychological
      performance in all major cognitive domains was obtained. Thalamic atrophy for the
      patients with MS was determined via third ventricular width measurement. RESULTS:
      The MS group had a greater number of overall violations, administrative
      violations, and nonmoving safety violations. The groups differed on
      neuropsychological tasks measuring visuospatial skills, speeded language,
      learning, and executive functioning, after controlling for affective symptoms.
      Third ventricular width was associated with total violations as well as moving
      safety violations. Finally, third ventricular width accounted for a significant
      variance in driving violation frequency above and beyond demographic variables
      and neuropsychological factors. CONCLUSIONS: There is an increased frequency of
      motor vehicle violations among patients with multiple sclerosis, and the number
      of violations can be predicted by thalamic brain atrophy.

PMID- 24929026
TI  - Long-term trajectories of health-related quality of life in individuals with
      cerebral palsy: a multicenter longitudinal study.
AB  - OBJECTIVES: To (1) determine the long-term trajectory of health-related quality
      of life (HRQOL) for the dimensions of physical complaints and motor,
      psychological, and social functioning for groups of individuals with cerebral
      palsy (CP) aged 1 to 24 years; (2) assess the variability in HRQOL within
      individuals with CP over time; (3) assess the variability in HRQOL between
      individuals with CP; and (4) compare the HRQOL in individuals with CP to
      reference data of typically developing individuals. DESIGN: Multicenter
      prospective longitudinal study. SETTING: Rehabilitation departments of 3
      university medical centers and various rehabilitation centers in The Netherlands.
      PARTICIPANTS: Dutch individuals with CP (N=424; age, 1-24y). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The HRQOL dimensions of physical complaints
      and motor, psychological, and social functioning. Each individual visited the
      rehabilitation department for 3 or 4 measurements. The time between measurements
      was 1 or 2 years. RESULTS: Individuals with CP experience an HRQOL that, on
      average, remains fairly stable over time. Variability in HRQOL within individuals
      with CP was similar to that within typically developing individuals. Variability
      between individuals with CP could be explained by type of CP (motor functioning),
      Gross Motor Function Classification System level (physical complaints and motor
      and social functioning), and intellectual disability (physical complaints and
      social functioning). Finally, individuals with CP experienced a lower HRQOL than
      did typically developing individuals, especially for the dimensions of motor and
      social functioning. CONCLUSIONS: Many changes take place in the psychosocial
      development of the individual with CP, which accordingly change their
      expectations and those of their caregivers, peers, and professionals. As a
      result, perceived physical complaints and motor, psychological, and social
      functioning remain fairly stable over many years.

PMID- 24929027
TI  - Role of Marsupenaeus japonicus crustin-like peptide against Vibrio penaeicida and
      white spot syndrome virus infection.
AB  - Crustins are important AMP that has been identified in crustaceans. In this
      study, the role of Marsupenaeus japonicus crustin-like peptide (MjCRS) was
      examined in vivo by RNA interference (RNAi) using double-stranded RNA (dsRNA).
      Tissue expression analysis revealed that MjCRS transcripts are expressed in
      different tissues tested with the highest expression observed in hemocytes.
      Treatment with double-stranded RNA specific to MjCRS led to a significant
      reduction of MjCRS transcripts within the hemocytes. When MjCRS was silenced and
      subsequently infected with Vibrio penaeicida final mortality was significantly
      higher compared with PBS and dsGFP treated groups. On the other hand, final
      mortalities of MjCRS silenced and PBS injected groups were not significantly
      different after infection with white spot virus, however, both are significantly
      higher compared with dsGFP treated group. V. penaeicida infection significantly
      decreased MjCRS expression at 3, 6, 12 and 24h followed by significant increase
      at 48 h post-infection. On the contrary, white spot infection significantly
      increased MjCRS expression at 6 and 12h and decreased at 48 h post-infection.
      dsRNA treatment alone decreased total hemocyte counts (THCs) and subsequent V.
      penaeicida or white spot virus infection further decreased THCs. VP28 gene
      expression was both similarly increased in PBS injected group and MjCRS silenced
      group at 24 and 48 h-post infection. Results suggest that MjCRS is involved in
      antibacterial defense and might not have critical function against viral
      infection.

PMID- 24929028
TI  - Pretreatment information on dysphagia: exploring the views of head and neck
      cancer patients.
AB  - CONTEXT: Swallowing difficulties (dysphagia) are a common acute and chronic side
      effect of head and neck cancer (HNC) treatment. Dysphagia is associated with
      medical concerns such as malnutrition and pulmonary health as well as quality of
      life outcomes. Providing information on the likely changes to swallowing is an
      important component of pretreatment preparation. There is little research
      providing the patients' perspective in this area. OBJECTIVES: This is a
      qualitative study to describe patients' views on pretreatment information
      regarding changes to eating, drinking, and swallowing after chemoradiotherapy
      treatment for HNC. METHODS: A purposive sample of 24 patients with HNC with a
      range of post-treatment dysphagia severity, up to two years after
      chemoradiotherapy, was selected to participate in focus groups or semistructured
      interviews. Thematic analysis was conducted by two researchers, and results were
      verified with three participants. RESULTS: Half of the participants presented
      with mild dysphagia, with the remainder having moderate to severe dysphagia. Mean
      age was 59 years, and mean time post-treatment was 10 months. Data were grouped
      into three main themes and subthemes: expectations about treatment outcomes and
      whether information correlated with pretreatment information; presentation of
      information, including the format and delivery; and the difficulties with
      absorption and retention of information. CONCLUSION: Patients require information
      on the impact and prognosis for their swallowing ability. There was a general
      preference for verbal information, from someone knowledgeable about dysphagia.
      However, there are also individual preferences for the manner and pace at which
      this information is delivered. Further research is indicated to explore ways of
      providing information that is individually tailored to patients' needs and
      preferences.

PMID- 24929029
TI  - Complexities in euthanasia or physician-assisted suicide as perceived by Dutch
      physicians and patients' relatives.
AB  - CONTEXT: The practice of euthanasia and physician-assisted suicide (EAS) is
      always complex, but some cases are more complex than others. The nature of these
      unusually complex cases is not known. OBJECTIVES: To identify and categorize the
      characteristics of EAS requests that are more complex than others. METHODS: We
      held in-depth interviews with 28 Dutch physicians about their perception of
      complex cases of EAS requests. We also interviewed 26 relatives of patients who
      had died by EAS. We used open coding and inductive analysis to identify various
      different aspects of the complexities described by the participants. RESULTS:
      Complexities can be categorized into relational difficulties-such as
      miscommunication, invisible suffering, and the absence of a process of growth
      toward EAS-and complexities that arise from unexpected situations, such as the
      capricious progress of a disease or the obligation to move the patient. The
      interviews showed that relatives of the patient influence the process toward EAS.
      CONCLUSION: First, the process toward EAS may be disrupted, causing a complex
      situation. Second, the course of the process toward EAS is influenced not only by
      the patient and his/her attending physician but also by the relatives who are
      involved. Communicating and clarifying expectations throughout the process may
      help to prevent the occurrence of unusually complex situations.

PMID- 24929030
TI  - Why people accept opioids: role of general attitudes toward drugs, experience as
      a bereaved family, information from medical professionals, and personal beliefs
      regarding a good death.
AB  - CONTEXT: Many surveys have evaluated patient-related barriers to pain management.
      OBJECTIVES: To explore associations between a preference for opioids and general
      attitudes toward drugs, the experience and information received as a bereaved
      family, and beliefs regarding a good death. METHODS: A cross-sectional survey,
      performed in 2010, of bereaved families of patients with cancer in palliative
      care units across Japan. Questionnaires were sent to 997 families. RESULTS: A
      total of 66% of families responded. Of these, 224 responses were excluded because
      the family declined to participate in the study (n = 38), the patient was not
      receiving any opioid analgesics, and there were missing data (n = 164), or data
      were missing for the primary end points (n = 22). Thus, 432 responses were
      finally analyzed (43%). In total, 26%, 41%, and 31% of family members stated that
      they strongly want to receive, want to receive, or slightly want to receive
      opioids if needed in the future, respectively. Determinants associated with a
      preference for receiving opioid treatment were the following: a general
      appreciation of the drugs (P = 0.005), witnessing an improvement in the patient's
      quality of life as a result of pain relief (P = 0.003), information provided by
      medical professionals that the opioid could be discontinued if side effects
      developed (P = 0.042), and the belief that a good death was one that was free
      from pain and physical distress (P < 0.001). CONCLUSION: More than 90% of
      bereaved families whose relatives were treated with opioid analgesics reported a
      preference to receive opioid analgesics for the treatment of cancer pain, if
      necessary, in the future.

PMID- 24929032
TI  - Temporal and spatial expression of the four Igf ligands and two Igf type 1
      receptors in zebrafish during early embryonic development.
AB  - The insulin-like growth factor (Igf) family is an evolutionarily conserved system
      essential for normal growth and development in vertebrates. Unlike mammals, four
      distinct Igf ligands (Igf1, Igf2a, Igf2b and Igf3) and two Igf type 1 receptors
      (Igf1ra and Igf1rb) are present in zebrafish. However, the localization of these
      multiple ligands and receptors especially the recently discovered igf3 during
      early development of zebrafish is poorly understood. In this study, detailed
      expression patterns of these components of the Igf system during embryogenesis of
      zebrafish were analyzed. It was found that igf1 is specifically expressed in the
      trigeminal ganglia region from 18 hpf to 72 hpf, while igf2a is restricted to the
      caudal regions of the notochord from 14 hpf to 18 hpf as well as in the midbrain,
      dorsal hind brain and otic vesicle at 24 hpf. On the other hand, igf2a is highly
      expressed in the midbrain and pharyngeal arch region at 48 hpf, followed by its
      appearance in the liver and brain at 72 hpf, while igf2b is restricted to the
      floor plate and hypochord from 12 hpf to 18 hpf, and strong expression is also
      detected in the midbrain and dorsal hind brain at 24 hpf. The teleost specific
      igf3 is highly expressed in the pharyngeal arch region before 24 hpf, but is then
      restricted to the sternohyoideus after 48 hpf. The receptor subtype igf1ra is
      ubiquitously expressed before 24 hpf but is confined to the brain at 72 hpf.
      However, igf1rb is widely expressed before 10 hpf, but is more confined to the
      brain region at 24 hpf and 72 hpf. This dynamic temporal-spatial expression
      during embryogenesis of zebrafish, together with the unique and overlapping
      expression patterns of the Igf ligands and receptors suggest the coordination of
      the divergent functions of the Igf system during early development in zebrafish.

PMID- 24929031
TI  - A comprehensive analysis of aquaporin and secretory related gene expression in
      neonate and adult cholangiocytes.
AB  - Canalicular bile is secreted by hepatocytes and then passes through the
      intrahepatic bile ducts, comprised of cholangiocytes, to reach the extrahepatic
      biliary system. In addition to providing a conduit for bile to drain from the
      liver, cholangiocytes play an active role in modifying bile composition. Bile
      formation is the result of a series of highly coordinated intricate membrane
      transport interactions. Proper systematic regulation of solute and water
      transport is critical for both digestion and the health of the liver, yet our
      knowledge of cholangiocyte water and ion transporters and their relative
      expression patterns remains incomplete. In this report, we provide a
      comprehensive expression profile of the aquaporin (AQP) family and three
      receptors/channels known to regulate ion transport in the murine cholangiocyte.
      In murine intrahepatic cholangiocytes, we found mRNA expression for all twelve of
      the members of the AQP family of proteins and found temporal changes in the
      expression profile occurring with age. Using AQP4, an established marker within
      cholangiocyte physiology, we found that AQP2, AQP5 and AQP6 expression levels to
      be significantly different between the neonatal and adult time points.
      Furthermore, there were distinct temporal expression patterns, with that of AQP12
      unique in that its expression level decreased with age, whilst the majority of
      AQPs followed an increasing expression level trend with age. Of the three
      receptors/channels regulating ion transport in the murine cholangiocyte, only the
      cystic fibrosis transmembrane conductance regulator was found to follow a
      consistent trend of decreasing expression coincident with age. We have further
      validated AQP3 and AQP8 protein localization in both hepatocytes and
      cholangiocytes. This study emphasizes the need to further appreciate and consider
      the differences in cholangiocyte biology when treating neonatal and adult
      hepatobiliary diseases. 

PMID- 24929033
TI  - Expression pattern and first functional characterization of riok-1 in
      Caenorhabditis elegans.
AB  - Rio kinases are atypical serine/threonine kinases that emerge as potential
      cooperation partners in Ras-driven tumors. In the current study, we performed an
      RNAi screen in Caenorhabditis elegans to identify suppressors of oncogenic Ras
      signaling. Aberrant Ras/Raf signaling in C. elegans leads to the formation of a
      multi-vulva (Muv) phenotype. We found that depletion of riok-1, the C. elegans
      orthologue of the mammalian RioK1, suppressed the Muv phenotype. By using a
      promoter GFP construct, we could show that riok-1 is expressed in neuronal cells,
      the somatic gonad, the vulva, the uterus and the spermatheca. Furthermore, we
      observed developmental defects in the gonad upon riok-1 knockdown in a wildtype
      background. Our data suggest that riok-1 is a modulator of the Ras signaling
      pathway, suggesting implications for novel interventions in the context of Ras
      driven tumors. 

PMID- 24929034
TI  - Editor's perspectives - July 2014.

PMID- 24929035
TI  - Clinical presentation and diagnosis of toxoplasmic encephalitis in Japan.
AB  - Distinguishing life-threatening toxoplasmic encephalitis (TE) from brain lymphoma
      in patients with acquired immunodeficiency syndrome (AIDS) may be difficult.
      Empiric anti-toxoplasmosis treatment is often initiated because of the reluctance
      in performing brain biopsies, which may delay the diagnosis and treatment of
      brain lymphoma in Japan. In this study, we retrospectively examined the clinical
      characteristics of 13 AIDS patients with TE in Japan, including magnetic
      resonance imaging and thallium 201 (201TI) single photon emission computed
      tomography (SPECT) findings, cerebral spinal fluid analysis, serology, and
      polymerase chain reaction (PCR) results. All patients improved on anti
      toxoplasmosis treatment. Of the 11 patients who underwent serological testing, 6
      (55%) had a positive serological result. Of the 7 patients who underwent PCR
      testing, 3 (42.9%) had a positive PCR result. Nine of 11 patients with TE (81.8%)
      had multiple lesions. Analysis of the sites of TE lesions did not reveal a
      difference in site predilection between TE and brain lymphoma. Uptake was
      negative in all 9 patients who underwent 201Tl SPECT. The study findings suggest
      that toxoplasma serostatus and PCR may be used to discriminate TE from brain
      lymphoma. No focal accumulation of 201TI is strongly suggestive of TE in patients
      with AIDS in Japan. 

PMID- 24929036
TI  - Subjective adverse reactions to metronidazole in patients with amebiasis.
AB  - Subjective adverse reactions to metronidazole were analyzed in 111 patients with
      amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250
      mg and 75 patients at daily doses lower than 2250 mg. The reactions reported
      included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2
      (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%),
      numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in
      1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the
      patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the
      patients receiving lower daily doses. The duration of the metronidazole
      administration in days was not associated with the appearance of nausea. No life
      threatening adverse reactions were identified, and good clinical therapeutic
      effects were observed in 96% (107/111) of the patients. While metronidazole
      appears to be a safe anti-protozoal agent for patients with amebiasis, our
      results indicate that a daily metronidazole dose of 2250 mg is excessive for
      amebiasis, as it often induces nausea.

PMID- 24929037
TI  - A sequential co-extraction method for DNA, RNA and protein recovery from soil for
      future system-based approaches.
AB  - A co-extraction protocol that sequentially isolates core biopolymer fractions
      (DNA, RNA, protein) from edaphic microbial communities is presented. In order to
      confirm compatibility with downstream analyses, bacterial T-RFLP profiles were
      generated from the DNA- and RNA-derived fractions of an arid-based soil, with
      metaproteomics undertaken on the corresponding protein fraction. 

PMID- 24929038
TI  - Solid lipid excipients - matrix agents for sustained drug delivery.
AB  - Lipid excipients are attracting interest from drug developers due to their
      performance, ease of use, versatility and their potential to generate
      intellectual property through innovation in drug delivery particularly in the
      case of modifying drug release systems. Many articles have described the use of
      lipid excipients to develop matrix modified release dosage forms in a range of
      processing techniques, therefore a comprehensive review is timely to collect
      together and analyze key information. This review article focuses on the utility
      of lipid excipients in solid sustained drug delivery systems with emphasis on the
      efficiency and robustness of these systems with respect to: (i) the choice of the
      manufacturing process and impact on drug release, (ii) the fundamental drug
      release mechanisms, (iii) resistance of the drug formulation under physiological
      conditions and (iv) long-term stability. Understanding the functionality of these
      versatile excipients in formulation is elementary for the development of highly
      robust lipid-based sustained release medicines. 

PMID- 24929040
TI  - Lag phase-associated iron accumulation is likely a microbial counter-strategy to
      host iron sequestration: role of the ferric uptake regulator (fur).
AB  - Iron is an essential metal for almost all forms of life, but potentiates
      oxidative stress via Fenton catalysis. During microbial lag phase there is a
      rapid influx of iron with concomitant oxidative hypersensitivity. How and why
      iron accumulation occurs remains to be elucidated. Iron homeostasis in
      prokaryotes is mediated by the ferric uptake regulator (Fur), an iron-activated
      global regulator that controls intracellular iron levels by feedback inhibition
      with the metal. Herein it is postulated, based on the expression profiles of
      antioxidant enzymes within the Fur regulon as observed in wild type and Deltafur
      mutants, that iron accumulation is mediated by a transitively low concentration
      of the Fur protein during lag phase. Vertebrate hosts sequester iron upon
      'sensing' an infection in order to retard microbial proliferation through a
      process known as 'nutritional immunity'. It is herein argued that the purpose of
      iron accumulation is not principally a preparative step for the replicative
      phase, as suggested elsewhere, but an evolved behavior that counteracts host iron
      sequestration. This interpretation is supported by multiple clinical and animal
      studies that demonstrate that iron surplus in hosts advances progression and
      susceptibility to infection, and vice versa. Contextualizing iron accumulation as
      a counter-immune behavior adds impetus to the development of antibiotics
      targeting pathogenic modes of iron acquisition. 

PMID- 24929041
TI  - A computational model of nuclear self-organisation in syncytial embryos.
AB  - Syncytial embryos develop through cycles of nuclear division and rearrangement
      within a common cytoplasm. A paradigm example is Drosophila melanogaster in which
      nuclei form an ordered array in the embryo surface over cell cycles 10-13. This
      ordering process is assumed to be essential for subsequent cellularisation. Using
      quantitative tissue analysis, it has previously been shown that the regrowth of
      actin and microtubule networks after nuclear division generates reordering forces
      that counteract its disordering effect (Kanesaki et al., 2011). We present here
      an individual-based computer simulation modelling the nuclear dynamics. In
      contrast to similar modelling approaches e.g. epithelial monolayers or tumour
      spheroids, we focus not on the spatial dependence, but rather on the time
      dependence of the interaction laws. We show that appropriate phenomenological
      inter-nuclear force laws reproduce the experimentally observed dynamics provided
      that the cytoskeletal network regrows sufficiently quickly after mitosis. Then
      repulsive forces provided by the actin system are necessary and sufficient to
      regain the observed level of order in the system, after the strong disruption
      resulting from cytoskeletal network disassembly and spindle formation. We also
      observe little mixing of nuclei through cell cycles. Our study highlights the
      importance of the dynamics of cytoskeletal forces during this critical phase of
      syncytial development and emphasises the need for real-time experimental data at
      high temporal resolution. 

PMID- 24929039
TI  - Injectable controlled release depots for large molecules.
AB  - Biodegradable, injectable depot formulations for long-term controlled drug
      release have improved therapy for a number of drug molecules and led to over a
      dozen highly successful pharmaceutical products. Until now, success has been
      limited to several small molecules and peptides, although remarkable improvements
      have been accomplished in some of these cases. For example, twice-a-year depot
      injections with leuprolide are available compared to the once-a-day injection of
      the solution dosage form. Injectable depots are typically prepared by
      encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that
      is used in children every day as a resorbable suture material, and therefore,
      highly biocompatible. PLGAs remain today as one of the few "real world"
      biodegradable synthetic biomaterials used in US FDA-approved parenteral long
      acting-release (LAR) products. Despite their success, there remain critical
      barriers to the more widespread use of PLGA LARproducts, particularly for
      delivery of more peptides and other large molecular drugs, namely proteins. In
      this review, we describe key concepts in the development of injectable PLGA
      controlled-release depots for peptides and proteins, and then use this
      information to identify key issues impeding greater widespread use of PLGA depots
      for this class of drugs. Finally, we examine important approaches, particularly
      those developed in our research laboratory, toward overcoming these barriers to
      advance commercial LAR development. 

PMID- 24929042
TI  - Salidroside induces neuronal differentiation of mouse mesenchymal stem cells
      through Notch and BMP signaling pathways.
AB  - Salidroside (p-hydroxyphenethyl-beta-D-glucoside, SAL), a phenylpropanoid
      glycoside isolated from a popular traditional Chinese medicinal plant Rhodiola
      rosea L., possesses multiple pharmacological actions. Previous study showed that
      SAL could induce rat mesenchymal stem cells (MSCs) to differentiate into
      dopaminergic neurons and induce mouse MSCs D1 to differentiate into neuronal
      cells. However, the mechanisms of SAL-induced neuronal differentiation of MSCs
      still need investigation. In this study, we observed the effects of SAL on
      neuronal differentiation of D1 cells and the possible involvement of Notch and
      BMP signaling pathways. SAL inhibited the proliferation, induced neuronal
      phenotypes, and upregulated the expressions of neuronal-specific marker
      molecules, such as neuronal enolase 2 (Eno2/NSE), microtubule-associated protein
      2 (MAP2), and beta 3 class III tubulin (Tubb3/beta-tubulin III) in D1 cells. SAL
      not only downregulated the expressions of Notch1 and hairy enhancer of split 1
      (Drosophila) (Hes1) but also upregulated the expression of Smad1/5/8 and its
      phosphorylation (p-Smad 1/5/8). The neuronal differentiation effects of SAL on D1
      cells were promoted by a Notch signaling antagonist, DAPT, but attenuated by a
      BMP signaling pathway antagonist, Noggin. Our findings suggest that SAL might be
      promising in inducing neuronal differentiation of mouse MSCs mediated by both
      Notch signaling pathway and BMP signaling pathway.

PMID- 24929043
TI  - Synthetic peptides for efficient discrimination of anti-enterovirus antibodies at
      the serotype level.
AB  - Enteroviruses are important human pathogens, causing a broad spectrum of diseases
      from minor common colds to fatal myocarditis. However, certain disease syndromes
      are caused by one or few serotypes. Serotype identification is difficult due to
      the laborious neutralization tests that lack of sensitivity, while in commercial
      ELISAs homotypic antibodies' activities are largely masked by the recognition of
      genera-specific epitopes by heterotypic antibodies. In the present study
      homotypic assays were developed with the ability to discriminate different
      enterovirus serotypes. Seventy-three children sera, positive for IgM antibodies
      against enterovirus genus and 49 healthy children were examined for the presence
      of antibodies against 14 synthetic peptides derived from a non-conserved region
      of the VP1 protein of coxsackieviruses B2, B3, B4, B5, A9, A16, A24, echoviruses
      6, 7, 9, 11, 30, enterovirus 71 and parechovirus 1. 50% of the anti-enterovirus
      IgM positive sera (>150 BU) reacted with the peptides with the majority of them
      to preferentially recognize one of them, supporting the homotypic nature of our
      assay. Inhibition studies yielded homologous inhibition rates 67-95% suggesting
      that specific peptide recognition actually occurred. The diagnostic value of our
      assay was tested in blood samples drawn over a 1.5-year period from a 5-year old
      patient. The anti-enterovirus reactivity was clearly attributed to echovirus
      serotype 11. The IgM/IgG antibody ratio was reversed 4 months later and
      subsequently IgM antibodies dropped below the cutoff point. In this paper we
      demonstrate that our assay can be used to discriminate between antibodies
      targeting different enterovirus serotypes.

PMID- 24929044
TI  - Development of conjugated estrogens/bazedoxifene, the first tissue selective
      estrogen complex (TSEC) for management of menopausal hot flashes and
      postmenopausal bone loss.
AB  - Conjugated estrogens (CE) combined with the selective estrogen receptor modulator
      (SERM) bazedoxifene (BZA) is a new option for alleviating menopausal symptoms and
      preventing postmenopausal bone loss. The rationale for developing the tissue
      selective estrogen complex (TSEC) CE/BZA was to combine CE's benefits with the
      SERM's tissue-specific properties to offset estrogenic stimulation of endometrial
      and breast tissue. TSECs provide a progestin-free alternative to traditional
      estrogen-progestin therapy (EPT) in women with a uterus. Preclinical studies
      supported bazedoxifene as the SERM of choice and demonstrated that CE/BZA
      provided an optimal balance of estrogen receptor agonist/antagonist activity
      compared with other potential TSEC pairings. Initial clinical development of
      CE/BZA focused on determining the appropriate dose ratio that would demonstrate
      efficacy with minimal to no stimulation of the breast or endometrium. Clinical
      studies confirmed the efficacy of the selected doses for maintaining bone mass;
      relieving vasomotor symptoms, vulvar-vaginal atrophy, and dyspareunia; and
      improving sexual function in postmenopausal women. Reduction of hot flashes also
      translated into improved menopause-specific quality of life and sleep. Unlike
      EPT, the FDA-approved dose of CE 0.45 mg/BZA 20mg does not cause a change in
      breast density or the endometrium, or increase breast pain compared with placebo.
      In clinical trials up to 2 years, CE 0.45 mg/BZA 20 mg has a favorable
      tolerability profile and rates of coronary heart disease, venous thromboembolism,
      and amenorrhea similar to placebo. Therefore, CE 0.45 mg/BZA 20 mg is an
      effective, well-tolerated alternative to EPT for menopausal symptom relief and
      osteoporosis prevention for postmenopausal women with a uterus.

PMID- 24929045
TI  - Synthesis of novel anticancer agents through opening of spiroacetal ring of
      diosgenin.
AB  - Diosgenin has been modified to furostane derivatives after opening the F
      spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly
      transformed to the ketone 9. The structure of ketone 9 was confirmed by
      spectroscopy and finally by X-ray crystallography. Five of the diosgenin
      derivatives showed significant anticancer activity against human cancer cell
      lines. The most potent molecule of this series i.e. compound 7, inhibited
      cellular growth by arresting the population at G0/G1 phase of cell division
      cycle. Cells undergo apoptosis after exposure to the derivative 7 which was
      evident by increase in sub G0 population in cell cycle analysis. Docking
      experiments showed caspase-3 and caspase-9 as possible molecular targets for
      these compounds. This was further validated by cleavage of PARP, a caspase target
      in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in
      acute oral toxicity in Swiss albino mice. 

PMID- 24929046
TI  - Selective estrogen-induced apoptosis in breast cancer.
AB  - Antihormone therapy remains the gold standard of care in the treatment of
      estrogen receptor (ER) positive breast cancer. However, development of acquired
      long term antihormone resistance exposes a vulnerability to estrogen that induces
      apoptosis. Laboratory and clinical studies indicate that successful therapy with
      estrogens is dependent on the duration of estrogen withdrawal and menopausal
      status of a woman. Interrogation of estradiol (E2) induced apoptosis using
      molecular studies indicate treatment of long term estrogen deprived MCF-7 breast
      cancer cells with estrogen causes an endoplasmic reticulum stress response that
      induces an unfolded protein response signal to inhibit protein translation. E2
      binds to the ER and mediates apoptosis through the classical genomic pathway.
      Furthermore, the induction of apoptosis by estrogens is dependent on the
      conformation of the estrogen-ER complex. In this review, we explore the mechanism
      and the processes involved in the paradox of estrogen induced apoptosis and the
      new selectivity of estrogen action on different cell populations that is
      correctly been deciphered for clinical practice. 

PMID- 24929047
TI  - Asterosaponins from the Far Eastern starfish Leptasterias ochotensis and their
      anticancer activity.
AB  - Six new asterosaponins, leptasteriosides A-F (3-8), one new and one previously
      known asterogenins (1, 2) were isolated from the alcoholic extract of the Far
      Eastern starfish Leptasterias ochotensis. The structures of 1-8 were elucidated
      by extensive NMR and ESI-MS techniques. Compounds 2-8 showed slight or moderate
      cytotoxic activities against cancer cell lines RPMI-7951 and T-47D. The
      asterosaponins 3-5 demonstrated a significant inhibition of RPMI-7951 and T-47D
      cell colony formation in soft agar clonogenic assay in nontoxic doses. 

PMID- 24929049
TI  - The possible role of hydrogen sulfide as a modulator of hemostatic parameters of
      plasma.
AB  - Hydrogen sulfide (H2S) is a well known toxic gas at high levels. However, at
      physiological levels, H2S may play a role in the pathogenesis of various
      cardiovascular diseases. The objective was to study the effects of exogenous H2S
      on the hemostatic parameters (coagulation and fibrinolytic activity) of human
      plasma. Human plasma was incubated (5, 15 and 30 min) with NaHS as a H2S donor at
      the final concentration of 0.01-100 MUM. Hemostatic factors, such as maximum
      velocity of clot formation, fibrin lysis half-time, the activated partial
      thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were
      estimated. Moreover, the aim of our study was to establish the influence of NaHS
      (10 MUM; 5, 15 and 30 min) on the clot formation using the purified fibrinogen.
      We demonstrated that coagulation/fibrinolytic properties of human plasma
      incubated with NaHS were changed. APPT, PT and TT of plasma treated with NaHS at
      tested concentrations--0.01-100 MUM were prolonged. We observed that NaHS (0.01
      100 MUM) reduced fibrin polymerization in whole plasma and 10 MUM NaHS also
      reduced polymerization of purified fibrinogen. In the presence of NaHS (at the
      low tested concentration--1 MUM) the decrease was about 18% (in plasma, p<0.05).
      Our experiments also showed that NaHS (0.01-100 MUM) stimulated the fibrin lysis
      in whole plasma. However, the time-dependent (5, 15 and 30 min) reduction of
      fibrin/fibrinogen polymerization and stimulation of fibrin lysis by NaHS (10 MUM)
      was not observed. In conclusion, the present study demonstrates the anticoagulant
      properties of exogenous H2S in vitro.

PMID- 24929048
TI  - The conditioning and extinction of fear in youths: what's sex got to do with it?
AB  - Adult work shows differences in emotional processing influenced by sexes of both
      the viewer and expresser of facial expressions. We investigated this in 120
      healthy youths (57 boys; 10-17 years old) randomly assigned to fear conditioning
      and extinction tasks using either neutral male or female faces as the conditioned
      threat and safety cues, and a fearful face paired with a shrieking scream as the
      unconditioned stimulus. Fear ratings and skin conductance responses (SCRs) were
      assessed. Male faces triggered increased fear ratings in all participants during
      conditioning and extinction. Greater differential SCRs were observed in boys
      viewing male faces and in girls viewing female faces during conditioning. During
      extinction, differential SCR findings remained significant in boys viewing male
      faces. Our findings demonstrate how sex of participant and sex of target interact
      to shape fear responses in youths, and how the type of measure may lead to
      distinct profiles of fear responses. 

PMID- 24929050
TI  - Ruptured aneurysm of the splenic artery associated with fibromuscular dysplasia.
AB  - Rupture of a splenic artery aneurysm is a rare event associated with high
      mortality rates. Aneurysm of the splenic artery associated with fibromuscular
      dysplasia (FMD) is even rarer, with only 3 previously reported cases. We report a
      patient with previously undiagnosed FMD who required emergent intervention
      because of a ruptured splenic aneurysm. In discussion, we present an overview of
      literature on splenic aneurysms and FMD, together with pathology and treatment. 

PMID- 24929051
TI  - Endovascular repositioning of a migrated stent graft using "endoanchor capture".
AB  - Endovascular aneurysm repair is increasingly used to treat patients harboring
      abdominal aortic aneurysms with severe comorbidities that make them unfavorable
      candidates for open repair. Graft-related complications in these patients also
      require unique solutions. We report the novel technique of "endoanchor capture"
      for successful repositioning of a migrated stent graft. 

PMID- 24929052
TI  - Endometrial cancer: a review and current management strategies: part II.
AB  - Endometrial carcinoma is the most common gynecologic malignancy. A thorough
      understanding of the epidemiology, pathophysiology, and management strategies for
      this cancer allows the obstetrician-gynecologist to identify women at increased
      risk, contribute toward risk reduction, and facilitate early diagnosis. The
      Society of Gynecologic Oncology's Clinical Practice Committee has reviewed the
      literature through March of 2014 and created evidence-based practice
      recommendations for diagnosis and treatment. The level of recommendations used is
      based on the method used by the U.S. Preventive Services Task Force (A: There is
      good evidence to support the recommendation, B: There is fair evidence to support
      the recommendation, C: There is insufficient evidence to support the
      recommendation; however, the recommendation may be made on other grounds, D:
      There is fair evidence against the recommendation, E: There is good evidence
      against the recommendation.). It is not the purpose of this document to provide a
      complete review of the literature on all aspects of endometrial cancer. This
      article examines: * Adjuvant therapy, including radiation, vaginal brachytherapy,
      and chemotherapy * Therapy for advanced disease, including chemotherapy and
      radiation therapy alone and in combination as well as hormone therapy * Treatment
      for synchronous endometrial and ovarian cancer * Fertility-sparing treatment *
      Post-treatment patient surveillance * The role of hormone replacement therapy in
      the development of endometrial carcinoma * Novel targeted therapies.

PMID- 24929053
TI  - Non-linear assessment of anticancer activity of 17-picolyl and 17-picolinylidene
      androstane derivatives--chemometric guidelines for further syntheses.
AB  - The present paper deals with prediction of cytotoxic activity of 17-picolyl and
      17-picolinylidene androstane derivatives toward androgen receptor negative
      prostate cancer cell line (PC-3). The prediction was achieved applying artificial
      neural networks (ANNs) method on the basis of molecular descriptors. The most
      important descriptors (skin permeability (SP), Madin-Darby canine kidney cell
      permeability (MDCK) and universal salt solubility factor (S+SF)) were selected by
      using stepwise selection coupled with partial least squares method. The ANN
      modelling was carried out in order to obtain reliable models which can facilitate
      further synthesis of androstane derivatives with high antiproliferative activity
      toward PC-3 cell line. The modelling procedure resulted in three ANN models with
      the best statistical performance. The obtained results show that the established
      ANN models can be applied for required purpose. 

PMID- 24929054
TI  - GMP production and characterization of leucine zipper-tagged tumor necrosis
      factor-related apoptosis-inducing ligand (LZ-TRAIL) for phase I clinical trial.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent
      antitumor activity in a wide range of cancers without deleterious side effects on
      normal tissues. Several TRAIL derivatives have been developed to improve its
      pharmacokinetics and therapeutic effects through strategies such as adding a
      leucine zipper to increase the circulation half-life. To obtain clinical grade LZ
      TRAIL for phase I clinical trial, a single batch of 30 L bioreactor culture was
      performed using the Escherichia coli BL21 (DE3) strain expressing the recombinant
      LZ-TRAIL. A robust LZ-TRAIL production fermentation process was developed, which
      could be scaled up from 5L to 50 L, and had a titer of approximately 1.4 g/l. A
      four-step purification strategy was carried out to obtain a final product with
      over 95% purity and 45% yield. The final material was filter sterilized,
      aseptically vialed, and stored at 4 degrees C, and comprehensively characterized
      using multiple assays (vialed product was sterile, purity was 95%, aggregates
      were <5%, potency revealed IC50 of 9 nM on MDA-MB-231 cells, and the endotoxin
      level was <0.25 U/mg). The purity, composition, and functional activities of the
      molecule were confirmed. in vivo investigations indicated that LZ-TRAIL has
      better antitumor potency in three Xenograft tumor models compared to TRAIL (95
      281). LZ-TRAIL also showed improved pharmacokinetic and safety profiles in
      cynomolgus monkeys without abnormalities associated with drug exposure. In
      conclusion, the scalable synthesis of LZ-TRAIL is useful for production of phase
      I clinical trial material. These preclinical investigations warrant further
      clinical development of this product for cancer therapy.

PMID- 24929055
TI  - Different effects of lobeline on neuronal and muscle nicotinic receptors.
AB  - Lobeline is a plant alkaloid known to interact with cholinergic system. The
      effect of lobeline on neuronal alpha3beta4 receptors expressed in COS cells and
      muscle embryonic alphabetagammadelta receptors naturally expressed in TE671 cells
      was studied using a patch-clamp technique. Our results show that lobeline
      inhibited responses to acetylcholine in human embryonic muscle nicotinic receptor
      in a pseudo-noncompetitive manner. The responses of rat neuronal alpha3beta4
      receptors to a low concentration of acetylcholine were potentiated by a mixed
      occupation mechanism that corresponds to "competitive potentiation". This
      potentiation turned into voltage-dependent inhibition for alpha3beta4 receptors
      was activated by a high concentration of acetylcholine. 

PMID- 24929056
TI  - Ptena, but not Ptenb, reduces regeneration after spinal cord injury in adult
      zebrafish.
AB  - Based on the observation that the tumor suppressor gene PTEN (phosphatase and
      tensin homolog) reduces regeneration after spinal cord injury (SCI) as evidenced
      in the PTEN knockout mouse, we have investigated the function of Ptena and Ptenb,
      the two zebrafish homologs of mammalian PTEN, in adult zebrafish after spinal
      cord injury with the aim to assess the contribution of the two zebrafish genes to
      functional recovery in an animal species that spontaneously recovers from central
      nervous system injury. The inhibition of Ptena expression by antisense morpholino
      (MO) application improved spinal cord regeneration through 4 to 5weeks after
      injury. Retrograde tracing showed regrowth of axons from neurons of the
      regeneration-competent nucleus of the medial longitudinal fascicle in the
      brainstem in the Ptena MO-treated fish. Ptenb MO-treated fish recovered as well
      as control MO-treated fish at 4 and 5weeks after SCI, with their locomotion being
      similar to that of sham-injured and non-injured fish. The mRNA levels of Ptena
      were upregulated after SCI at the early stage after injury (12h and 6days) caudal
      to the lesion site, compared to the non-injured control, while the levels of
      Ptenb were upregulated only at 12h after injury. In situ hybridization
      experiments were in agreement with the qPCR measurements. At the protein level,
      Ptena was found to be expressed in spinal motoneurons and immature neurons. These
      results indicate that Ptena, but not Ptenb, inhibits regeneration in zebrafish,
      thus sharing this feature with PTEN in mammals. The fact that zebrafish
      regenerate better than mammals despite the inhibitory presence of Ptena is likely
      due to regeneration-conducive molecules that tip the balance from inhibition to
      enhancement. Interestingly, although Ptena and Ptenb have been shown to be
      functionally redundant in promoting the development of the fish larval central
      nervous system, they are not functionally redundant in the adult, suggesting that
      regeneration in fish is not predominantly due to the overall recapitulation of
      development. 

PMID- 24929057
TI  - Measurement of plasma protein and lipoprotein binding of pyrethroids.
AB  - INTRODUCTION: A simple, reliable procedure was developed to measure binding of
      pyrethroid insecticides to total proteins and lipoproteins of rat and human
      plasma. METHODS: The extent of binding of (14)C-labeled deltamethrin (DLM), cis
      permethrin (CIS) and trans-permethrin (TRANS) was quantified by a 3-step organic
      solvent extraction technique. Rat and human plasma samples, containing NaF to
      inhibit esterases, were spiked with a range of concentrations of each
      radiolabeled pyrethroid. Protein binding reached equilibrium within ~1h of
      incubation at 37 degrees C. The samples were extracted in turn with: isooctane to
      collect the unbound fraction; 2-octanol to extract the lipoprotein-bound
      fraction; and acetonitrile to obtain the protein-bound fraction. RESULTS:
      Absolute recoveries of DLM, CIS and TRANS ranged from 86 to 95%. Adherence of
      these very lipophilic chemicals to glass and plastic was minimized by using
      silanized glass vials and LoBind(r) plastic pipettes. The method's ability to
      distinguish lipoprotein from protein binding was confirmed by experiments with
      diazepam and cyclosporine, drugs that bind selectively to albumin and
      lipoproteins, respectively. DISCUSSION: This procedure was effectively utilized
      for studies of the species-dependence of plasma protein and lipoprotein binding
      of three pyrethroids for inclusion in physiologically-based pharmacokinetic
      models of pyrethroids for use in health risk assessments of the insecticides in
      children and adults.

PMID- 24929058
TI  - The clinical efficacy of short-term steroid treatment in multilevel anterior
      cervical arthrodesis.
AB  - BACKGROUND CONTEXT: Dysphagia is the most common complication of anterior
      cervical discectomy and fusion (ACDF), and it is closely related to prevertebral
      soft-tissue swelling (PSTS). A few studies have found that local or systemic
      methylprednisolone is effective against laryngopharyngeal edema and airway
      obstruction. PURPOSE: To assess the effectiveness of short-term use of systemic
      methylprednisolone in relieving dysphagia and decreasing PSTS during the
      hospitalization period. STUDY DESIGN: A prospective study. PATIENT SAMPLE: Forty
      patients who underwent multilevel (more than three levels) ACDF with same plate
      fixation. OUTCOME MEASURE: Radiologic and clinical measures. METHODS: Twenty of
      these patients were given 250 mg of methylprednisolone intravenously (IV) four
      times a day only for 24 hours after the operation (at 6-hour intervals), whereas
      the remaining 20 did not receive methylprednisolone and served as controls. We
      used the Bazaz scale to compare the degree of dysphagia between groups during the
      hospitalization period. We used the C-spine lateral view to assess the degree of
      pre- and postoperative PSTS from C2 to C7. At the final follow-up, we assessed
      the relationship between the occurrence of complications and steroid use.
      RESULTS: The degree of dysphagia according to the Bazaz scale was less severe in
      the group that received methylprednisolone (p values; postoperative Day [POD]
      2~5<.05, POD 6=.014, POD 7=.019). Prevertebral soft-tissue swelling was also
      significantly lower in the group that received methylprednisolone (p values; POD
      2~POD 5 <.005, POD 1=.061, POD 6=.007, POD 7=.091). The amount of PSTS and
      dysphagia did not differ according to sex, age, smoking history, or length of
      surgery. The period of hospitalization in the experimental group was shorter than
      in the control group. No complications related to steroid use were found at the
      final follow-up. CONCLUSIONS: The short-term use of systemic methylprednisolone
      after ACDF appears to be effective in relieving dysphagia and decreasing the
      PSTS. Furthermore, the short-term use of methylprednisolone was not associated
      with any adverse effects of short-term IV steroid usage, such as peptic ulcer
      disease or postoperative infection. The clinical use of methylprednisolone in
      relieving dysphagia and decreasing PSTS deserves consideration during the early
      postoperative period.

PMID- 24929059
TI  - Cellular bone matrices: viable stem cell-containing bone graft substitutes.
AB  - BACKGROUND CONTEXT: Advances in the field of stem cell technology have stimulated
      the development and increased use of allogenic bone grafts containing live
      mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is
      estimated that CBMs comprise greater than 17% of all bone grafts and bone graft
      substitutes used. PURPOSE: To critically evaluate CBMs, specifically their
      technical specifications, existing published data supporting their use, US Food
      and Drug Administration (FDA) regulation, cost, potential pitfalls, and other
      aspects pertaining to their use. STUDY DESIGN: Areview of literature. METHODS: A
      series of Ovid, Medline, and Pubmed-National Library of Medicine/National
      Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only
      articles in English journals or published with English language translations were
      included. Level of evidence of the selected articles was assessed. Specific
      technical information on each CBM was obtained by direct communication from the
      companies marketing the individual products. RESULTS: Five different CBMs are
      currently available for use in spinal fusion surgery. There is a wide variation
      between the products with regard to the average donor age at harvest, total
      cellular concentration, percentage of MSCs, shelf life, and cell viability after
      defrosting. Three retrospective studies evaluating CBMs and fusion have shown
      fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials
      are underway. No independent studies evaluating spinal fusion rates with the use
      of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria
      under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review.
      The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous
      challenges exist in regard to MSCs' survival, function, osteoblastic potential,
      and cytokine production once implanted into the intended host. CONCLUSIONS:
      Cellular bone matrices may be a promising bone augmentation technology in spinal
      fusion surgery. Although CBMs appear to be safe for use as bone graft
      substitutes, their efficacy in spinal fusion surgery remains highly inconclusive.
      Large, nonindustry sponsored studies evaluating the efficacy of CBMs are
      required. Without results from such studies, surgeons must be made aware of the
      potential pitfalls of CBMs in spinal fusion surgery. With the currently available
      data, there is insufficient evidence to support the use of CBMs as bone graft
      substitutes in spinal fusion surgery.

PMID- 24929060
TI  - Validity and reliability of computerized measurement of lumbar intervertebral
      disc height and volume from magnetic resonance images.
AB  - BACKGROUND CONTEXT: Magnetic resonance (MR) examinations of morphologic
      characteristics of intervertebral discs (IVDs) have been used extensively for
      biomechanical studies and clinical investigations of the lumbar spine.
      Traditionally, the morphologic measurements have been performed using time- and
      expertise-intensive manual segmentation techniques not well suited for analyses
      of large-scale studies.. PURPOSE: The purpose of this study is to introduce and
      validate a semiautomated method for measuring IVD height and mean sagittal area
      (and volume) from MR images to determine if it can replace the manual assessment
      and enable analyses of large MR cohorts. STUDY DESIGN/SETTING: This study
      compares semiautomated and manual measurements and assesses their reliability and
      agreement using data from repeated MR examinations. METHODS: Seven healthy
      asymptomatic males underwent 1.5-T MR examinations of the lumbar spine involving
      sagittal T2-weighted fast spin-echo images obtained at baseline, pre-exercise,
      and postexercise conditions. Measures of the mean height and the mean sagittal
      area of lumbar IVDs (L1-L2 to L4-L5) were compared for two segmentation
      approaches: a conventional manual method (10-15 minutes to process one IVD) and a
      specifically developed semiautomated method (requiring only a few mouse clicks to
      process each subject). RESULTS: Both methods showed strong test-retest
      reproducibility evaluated on baseline and pre-exercise examinations with strong
      intraclass correlations for the semiautomated and manual methods for mean IVD
      height (intraclass correlation coefficient [ICC]=0.99, 0.98) and mean IVD area
      (ICC=0.98, 0.99), respectively. A bias (average deviation) of 0.38 mm (4.1%, 95%
      confidence interval 0.18-0.59 mm) was observed between the manual and
      semiautomated methods for the IVD height, whereas there was no statistically
      significant difference for the mean IVD area (0.1%+/-3.5%). The semiautomated and
      manual methods both detected significant exercise-induced changes in IVD height
      (0.20 and 0.28 mm) and mean IVD area (5.7 and 8.3 mm(2)), respectively.
      CONCLUSIONS: The presented semiautomated method provides an alternative to time-
      and expertise-intensive manual procedures for analysis of larger, cross
      sectional, interventional, and longitudinal MR studies for morphometric analyses
      of lumbar IVDs.

PMID- 24929061
TI  - Oxidative stress and lung function profiles of male smokers free from COPD
      compared to those with COPD: a case-control study.
AB  - BACKGROUND: The mechanisms of smoking tobacco leading to chronic obstructive
      pulmonary disease (COPD) are beginning to be understood. However, conclusions
      about the role of blood or lung oxidative stress markers were disparate. AIMS: To
      investigate the oxidative stress in blood or lung associated with tobacco smoke
      and to evaluate its effect on pulmonary function data and its relation with
      physical activity. METHODS: It is a case-control study. Fifty-four male-smokers
      of more than five pack-years (PY) and aged 40-60 years were included (29 Non
      COPD, 16 COPD). Physical activity score was determined. Blood sample levels of
      malondialdehyde (MDA), protein-cys-SH (PSH), and Glutathione (GSH) were measured.
      Fractional exhaled nitric oxide (FeNO) and plethysmographic measurements were
      performed. Correlation coefficients (r) evaluated the association between
      oxidative stress markers and independent variables (plethysmographic data and
      physical activity score). RESULTS: Non-COPD (48 +/- 6 years) and COPD (49 +/- 5
      years) groups had similar tobacco consumption patterns, that is, 27 +/- 14 PY
      versus 30 +/- 19 PY, respectively. Compared to the Non-COPD group, the COPD group
      had significantly lower levels of GSH and PSH, that is, mean +/- SE were 40 +/- 6
      versus 25 +/- 5 ug/mL and 54 +/- 10 versus 26 +/- 5 ug/g of hemoglobin,
      respectively. However, MDA level and FeNO values were similar. In the COPD group,
      none of the oxidative stress markers was significantly correlated with
      plethysmographic data or physical activity score. In the Non-COPD group, GSH was
      significantly correlated with physical activity score (r = 0.47) and PSH was
      significantly correlated with total lung capacity (TLC) (r = -0.50), residual
      volume (r = 0.41), and physical activity score (r = 0.62). FeNO was significantly
      correlated with TLC of the COPD group (r = -0.48). CONCLUSION: Compared to the
      Non-COPD group, the COPD group had a marked decrease in blood antioxidant markers
      (GSH and PSH) but similar blood oxidant (MDA) or lung (FeNO) burden.

PMID- 24929062
TI  - Effects of orexin 2 receptor activation on apnea in the C57BL/6J mouse.
AB  - BACKGROUND: The hypothesis was that an orexin 2 receptor (OX2R) agonist would
      prevent sleep-related disordered breathing. METHODS: In C57BL/6J (B6) mice, body
      plethysmography was performed with and without EEG monitoring of state
      (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake
      states at baseline and with an intracerebroventricular administration of vehicle,
      4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCS OX2 29. RESULTS: A
      significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with
      the agonist. Expressed as a function of the change from baseline, there was a
      significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003,
      f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas
      during sleep from 29.7+/-4.7 (M+/-SEM) to 7.3+/-2.4 during sleep (p=0.001). There
      was also a reduction in apneas during wakefulness. Administration of the
      antagonist did not increase event rate over baseline levels. CONCLUSIONS: The B6
      mouse is a preclinical model of wake-and sleep-disordered breathing, and the
      orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will
      reduce events in sleep and also wakefulness.

PMID- 24929063
TI  - Consequences of gestational stress on GABAergic modulation of respiratory
      activity in developing newborn pups.
AB  - The GABAergic system modulates respiratory activity and undergoes substantial
      changes during early life. Because this maturation process is sensitive to
      stress, we tested the hypothesis that gestational stress (GS) alters development
      of GABAergic modulation of respiratory control in rat pups. The respiratory
      responses to the selective GABAA receptor agonist muscimol were compared between
      pups born to dams subjected to GS (bright light and predator odor; 20 min/day
      from G9 to G19) or maintained under standard (control) conditions. Respiratory
      activity was measured on 1 and 4 days old pups of both sexes using in vivo (whole
      body plethysmography) and in vitro (isolated brainstem-spinal cord preparation)
      approaches. In intact pups, muscimol injection (0.75 mg/kg; i.p.) depressed
      minute ventilation; this response was less in GS pups, and at P4, muscimol
      augmented minute ventilation in GS females. Bath application of muscimol (0.01
      0.5 MUM) onto brainstem preparations decreased inspiratory (C4) burst frequency
      and amplitude in a dose-dependent manner; the responsiveness decreased with age.
      However, GS had limited effects on these results. We conclude that the results
      obtained in vivo are consistent with our hypothesis and show that GS delays
      maturation of GABAergic modulation of respiratory activity. The differences in
      the results observed between experimental approaches (in vivo versus in vitro)
      indicate that the effect of prenatal stress on maturation of GABAergic modulation
      of respiratory control mainly affects the peripheral/metabolic components of the
      respiratory control system.

PMID- 24929064
TI  - Aging causes exacerbated ischemic brain injury and failure of sevoflurane post
      conditioning: role of B-cell lymphoma-2.
AB  - Aging is associated with exacerbated brain injury after ischemic stroke. Herein,
      we explored the possible mechanisms underlying the age-associated exacerbated
      brain injury after ischemic stroke and determined whether therapeutic
      intervention with anesthetic post-conditioning would provide neuroprotection in
      aged rats. Male Fisher 344 rats (young, 4 months; aged, 24 months) underwent 2h
      of middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion, with or
      without sevoflurane post-conditioning for 15 min immediately at the onset of
      reperfusion. Compared with young rats, aged rats showed larger infarct size,
      worse neurological scores and more TUNEL-positive cells in the penumbral cerebral
      cortex at 24h after MCAO. However, edema formation and motor coordination were
      similar in both groups. Sevoflurane reduced the infarct size, edema formation,
      and TUNEL-positive cells, and improved the neurological outcome in young rats but
      not in aged rats. Molecular studies revealed that basal expression of the anti
      apoptotic molecule B-cell lymphoma-2 (Bcl-2) in the brain was lower in aged rats
      compared with young rats before MCAO, while basal expression of the pro-apoptotic
      molecule Bcl-2-associated X protein (Bax) showed similar levels in both groups.
      MCAO reduced Bcl-2 expression and increased Bax expression in both groups;
      however, Bax increase was more pronounced in aged rats. In young rats,
      sevoflurane reversed the above MCAO-induced changes. In contrast, sevoflurane
      failed to enhance Bcl-2 expression but decreased Bax expression in aged rats.
      These findings suggest that aging-associated reduction in basal Bcl-2 expression
      in the brain contributes to increased neuronal injury by enhancing cell apoptosis
      after ischemic stroke. Sevoflurane post-conditioning failed to provide
      neuroprotection in aged rats, probably due to its inability to increase Bcl-2
      levels and prevent apoptosis in the brain.

PMID- 24929065
TI  - Microglial NADPH oxidase activation mediates rod cell death in the retinal
      degeneration in rd mice.
AB  - Accumulating evidence supports that nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase contributes to microglia-mediated neurotoxicity in the CNS
      neurodegenerative diseases. Several studies, including ours, suggest that
      microglial activation is involved in the retinal degeneration in the animal
      models of retinitis pigmentosa (RP). In the present study, we investigated the
      activation of NADPH oxidase in the rod degeneration in rd mice and further
      explored its role in the microglia-mediated photoreceptor apoptosis. Expression
      of gp91phox protein, a major subunit of NAPDH oxidase in the whole retina of rd
      mice at postnatal days (P) 8, 10, 12, 14, 16 and 18 was assessed by western blot
      analysis. Location of gp91phox in the rd retina at each age group and its
      cellular source were studied by immunohistochemical analysis and double labeling
      respectively. The generation of superoxide radicals in the rd retinas was
      demonstrated by intraperitoneal injection of hydroethidine. Apocynin was applied
      intraperitoneally in the rd mice from P8 to P14 to inhibit the activity of NAPDH
      oxidase and the outer nuclear layer (ONL) thickness was measured before and after
      apocynin treatment. Our results demonstrated that during the rod degenerative
      process, the expression of gp91phox started to increase in the outer part of rd
      retina at P10 and reached a peak at P14. Double labeling of gp91phox with CD11b
      showed co-localization of gp91phox in the retinal microglial cells. Increasing
      generation of superoxide radicals visualized by hydroethidine was noted at P8 and
      reached a peak at P14. Apocynin markedly reduced the production of superoxide
      radicals and preserved the rod cells. The results suggested that NADPH oxidase
      might play an important role in the rod degeneration in the rd mice. Inhibition
      of NAPDH oxidase could be a possible approach to treat RP in the early
      degenerative stage. 

PMID- 24929067
TI  - Three structurally similar odorants trigger distinct signaling pathways in a
      mouse olfactory neuron.
AB  - In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a
      single olfactory receptor gene. By calcium imaging of individual OSNs in intact
      mouse olfactory turbinates, we observed that a subset of OSNs (Ho-OSNs) located
      in the most ventral olfactory receptor zone can mediate distinct signaling
      pathways when activated by structurally similar ligands. Calcium imaging showed
      that Ho-OSNs were highly sensitive to 2-heptanone, heptaldehyde and cis-4
      heptenal. 2-heptanone-evoked intracellular calcium elevation was mediated by cAMP
      signaling while heptaldehyde triggered the diacylglycerol pathway. An increase of
      intracellular calcium evoked by cis-4-heptenal was due to a combination of
      activation mediated by the adenylate cyclase pathway and suppression generated by
      phospholipase C signaling. Pharmacological studies demonstrated that novel
      mechanisms were involved in the phospholipase C-mediated intracellular calcium
      changes. Binary-mixture studies and cross-adaptation data indicate that three
      odorants acted on the same olfactory receptor. The feature that an olfactory
      receptor mediates multiple signaling pathways was specific for Ho-OSNs and not
      established in another population of OSNs characterized. Our study suggests that
      distinct signaling pathways triggered by ligand-induced conformational changes of
      an olfactory receptor constitute a complex information process mechanism in
      olfactory transduction. This study has important implications beyond olfaction in
      that it provides insights of plasticity and complexity of G-protein-coupled
      receptor activation and signal transduction. 

PMID- 24929066
TI  - Differential cavitation, angiogenesis and wound-healing responses in injured
      mouse and rat spinal cords.
AB  - The vascular disruption, blood vessel loss and cavitation that occur at spinal
      cord injury (SCI) epicenters in mice and rats are different, but few studies have
      compared the acute SCI response in the two species. This is of interest since key
      elements of the rat SCI response are shared with humans. In this study, we
      investigated acute SCI responses and characterized changes in pro- and anti
      angiogenic factors and matrix deposition in both species. Cavitation was absent
      in mouse but the area of the lesion site was 21- and 27-fold larger at 8 and 15
      days post-lesion (dpl), respectively, in the rat compared to intact control. The
      absence of wound cavitation in the mouse was correlated with increased levels of
      immunoreactive pro-angiogenic, pro-matrix and pro-wound-healing factors, e.g.
      laminin, matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth
      factor-A (VEGF-A) within the wound, which were 6.0-, 2.9-, and 2.8-fold,
      respectively, higher in the mouse compared to rats at 8 dpl. Increased axonal
      sparing was observed after dorsal column (DC) injury, detected by higher levels
      of neurofilament 200 (NF200) immunoreactivity in the dorsal column of mice
      compared to rats at both T7 and T9 spinal segments. Despite similar post SCI
      deficits in plantar heat tests at 2h after injury (1.4- and 1.6-fold lower than
      control mice and rats, respectively), by 7 days the magnitude of these responses
      were comparable to sham-treated controls in both species, while no post-SCI
      changes in Von Frey hair filament test response were observed in either species.
      We conclude that the more robust angiogenesis/wound-healing response in the mouse
      attenuates post-injury wound cavitation. Although the spinal cord functions that
      were monitored post-injury were similarly affected in both species, we suggest
      that the quality of the angiogenesis/wound-healing response together with the
      diminished lesion size seen after mouse SCI may protect against secondary axon
      damage and create an environment more conducive to axon sprouting/regeneration.
      These results suggest the potential therapeutic utility of manipulating the
      angiogenic response after human SCI.

PMID- 24929068
TI  - Low-grade inflammation disrupts structural plasticity in the human brain.
AB  - Increased low-grade inflammation is thought to be associated with several
      neuropsychiatric disorders characterized by decreased neuronal plasticity. The
      purpose of the present study was to investigate the relationship between
      structural changes in the human brain during cognitive training and the intensity
      of low-grade peripheral inflammation in healthy individuals (n=56). A two-month
      training (30 min/day) with a platformer video game resulted in a significantly
      increased volume of the right hippocampal formation. The number of stressful life
      events experienced during the past year was associated with less pronounced
      enlargement of the hippocampus. However, the main predictor of hippocampal volume
      expansion was the relative peripheral expression of Nuclear Factor-kappaB (NF
      kappaB), a transcription factor playing a central role in the effect of pro
      inflammatory cytokines. Interleukin-6 (IL-6) and C-reactive protein levels were
      not related to hippocampal plasticity when NF-kappaB was taken into
      consideration. These results suggest that more intensive peripheral inflammation
      is associated with weaker neuronal plasticity during cognitive training.

PMID- 24929071
TI  - Molecular mechanisms of histone modification function.

PMID- 24929069
TI  - Maternal treatment with glucocorticoids modulates gap junction protein expression
      in the ovine fetal brain.
AB  - Gap junctions facilitate intercellular communication and are important in brain
      development. Connexins (Cx) comprise a transmembrane protein family that forms
      gap junctions. Cx-32 is expressed in oligodendrocytes and neurons, Cx-36 in
      neurons, and Cx-43 in astrocytes. Although single antenatal steroid courses are
      recommended for fetal lung maturation, multiple courses can be given to women at
      recurrent risk for premature delivery. We examined the effects of single and
      multiple glucocorticoid courses on Cx-32, Cx-36, and Cx-43 protein expressions in
      the fetal cerebral cortex, cerebellum, and spinal cord, and differences in Cx
      expression among brain regions under basal conditions. In the single-course
      groups, the ewes received dexamethasone (6 mg) or placebo as four intramuscular
      injections every 12h over 48 h. In the multiple-course groups, the ewes received
      the same treatment, once a week for 5 weeks starting at 76-78 days of gestation.
      Cx were measured by Western immunoblot on brain samples from 105 to 108-day
      gestation fetuses. A single dexamethasone course was associated with increases
      (P<0.05) in cerebral cortical and spinal cord Cx-36 and Cx-43 and multiple
      courses with increases in cerebellar and spinal cord Cx-36, and cerebral cortical
      and cerebellar Cx-43. Cx-32 did not change. Cx-32 was higher in the cerebellum
      than cerebral cortex and spinal cord, Cx-36 higher in the spinal cord than
      cerebellum, and Cx-43 higher in the cerebellum and spinal cord than cerebral
      cortex during basal conditions. In conclusion, maternal glucocorticoid therapy
      increases specific Cx, responses to different maternal courses vary among Cx and
      brain regions, and Cx expression differs among brain regions under basal
      conditions. Maternal treatment with glucocorticoids differentially modulates Cx
      in the fetal brain.

PMID- 24929070
TI  - Biallelic targeting of expressed genes in mouse embryonic stem cells using the
      Cas9 system.
AB  - Gene targeting - homologous recombination between transfected DNA and a
      chromosomal locus - is greatly stimulated by a DNA break in the target locus.
      Recently, the RNA-guided Cas9 endonuclease, involved in bacterial adaptive
      immunity, has been modified to function in mammalian cells. Unlike other site
      specific endonucleases whose specificity resides within a protein, the
      specificity of Cas9-mediated DNA cleavage is determined by a guide RNA (gRNA)
      containing an ~20 nucleotide locus-specific RNA sequence, representing a major
      advance for versatile site-specific cleavage of the genome without protein
      engineering. This article provides a detailed method using the Cas9 system to
      target expressed genes in mouse embryonic stem cells. In this method, a
      promoterless marker flanked by short homology arms to the target locus is
      transfected into cells together with Cas9 and gRNA expression vectors.
      Importantly, biallelic gene knockout is obtained at high frequency by only one
      round of targeting using a single marker.

PMID- 24929072
TI  - Novel drug targets for asthma and COPD: lessons learned from in vitro and in vivo
      models.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent
      respiratory diseases characterized by airway inflammation, airway obstruction and
      airway hyperresponsiveness. Whilst current therapies, such as beta-agonists and
      glucocorticoids, may be effective at reducing symptoms, they do not reduce
      disease progression. Thus, there is a need to identify new therapeutic targets.
      In this review, we summarize the potential of novel targets or tools, including
      anti-inflammatories, phosphodiesterase inhibitors, kinase inhibitors, transient
      receptor potential channels, vitamin D and protease inhibitors, for the treatment
      of asthma and COPD. 

PMID- 24929073
TI  - Airway and systemic oxidant-antioxidant dysregulation in asthma: a possible
      scenario of oxidants spill over from lung into blood.
AB  - Asthma is characterized by repeated episodes of airway obstruction and an ongoing
      cycle of airway inflammation. Reactive oxygen species (ROS) produced by
      inflammatory cells in the lung play a key role in the pathogenesis as well as
      amplification of inflammation in asthmatic airways. Several enzymatic and non
      enzymatic antioxidants are available in the lung and systemic circulation to
      counteract ROS-mediated damage on various biomolecules such as lipid membranes,
      proteins, and DNA; however during asthmatic inflammation these defenses are
      overwhelmed due to excessive production of ROS thereby leading to inflammatory
      events in the airways/systemic circulation. ROS-mediated damage may result in
      increased vascular permeability, mucus hypersecretion, smooth muscle contraction,
      epithelial shedding and impairment in the responsiveness of beta-adrenergic
      receptors. Strategies aimed to boost the endogenous antioxidants either through
      dietary or pharmacological intervention to redress oxidant-antioxidant imbalance
      in asthma is the current area of research in many laboratories throughout the
      world. This review aims at providing a comprehensive overview of the available
      literature on oxidative stress and antioxidants imbalance in asthma with a focus
      both on lung and blood components and bring forth correlations between lung/blood
      oxidative stress/antioxidant parameters and lung function. 

PMID- 24929074
TI  - Exploration of ecological factors related to the spatial heterogeneity of
      tuberculosis prevalence in P. R. China.
AB  - BACKGROUND: The current prevalence of tuberculosis (TB) in the People's Republic
      of China (P. R. China) demonstrates geographical heterogeneities, which show that
      the TB prevalence in the remote areas of Western China is more serious than that
      in the coastal plain of Eastern China. Although a lot of ecological studies have
      been applied in the exploration on the regional difference of disease risks,
      there is still a paucity of ecological studies on TB prevalence in P. R. China.
      OBJECTIVE: To understand the underlying factors contributing to the regional
      inequity of TB burden in P. R. China by using an ecological approach and, thus,
      aiming to provide a basis to eliminate the TB spatial heterogeneity in the near
      future. DESIGN: Latent ecological variables were identified by using exploratory
      factor analysis from data obtained from four sources, i.e. the databases of the
      National TB Control Programme (2001-2010) in P. R. China, the China Health
      Statistical Yearbook during 2002-2011, the China Statistical Yearbook during 2002
      2011, and the provincial government websites in 2013. Partial least squares path
      modelling was chosen to construct the structural equation model to evaluate the
      relationship between TB prevalence and ecological variables. Furthermore, a
      geographically weighted regression model was used to explore the local spatial
      heterogeneity in the relationships. RESULTS: The latent ecological variables in
      terms of 'TB prevalence', 'TB investment', 'TB service', 'health investment',
      'health level', 'economic level', 'air quality', 'climatic factor' and
      'geographic factor' were identified. With the exception of TB service and health
      levels, other ecological factors had explicit and significant impacts on TB
      prevalence to varying degrees. Additionally, each ecological factor had different
      impacts on TB prevalence in different regions significantly. CONCLUSION:
      Ecological factors that were found predictive of TB prevalence in P. R. China are
      essential to take into account in the formulation of locally comprehensive
      strategies and interventions aiming to tailor the TB control and prevention
      programme into local settings in each ecozone.

PMID- 24929075
TI  - Cognitive and behaviour dysfunction of children with neurocysticercosis: a cross
      sectional study.
AB  - Eighty-three confirmed cases of neurocysticercosis diagnosed as per modified
      delBrutto criteria were enrolled in the study (Group-I) to observe cognitive and
      behavioural changes. Controls consisted of two groups: children with idiopathic
      generalized tonic-clonic seizure (Group-II) and normal children with non-specific
      cough (Group-III). Cases and controls were subjected to cognitive and behaviour
      assessment. There was significant difference in the intelligence quotient (IQ) of
      cases in domains of visual perception, immediate recall, analysis synthesis and
      reasoning, verbal ability, memory and spatial ability. In the age group of 6-18
      years, cases had significantly more behaviour problems than control without
      seizure, in domains of anxious depressed, withdrawn depressed, somatic problems,
      social problems and rule-breaking behaviour. Neurocysticercosis causes decline in
      cognitive function and behaviours in older children, which should be recognized
      early for appropriate management and to avoid undue parental anxiety. 

PMID- 24929076
TI  - Infectious causes of childhood disability: results from a pilot study in rural
      Bangladesh.
AB  - PURPOSE: To identify the contribution of infectious aetiologies to major
      childhood disabilities in Bangladesh. METHODS: Active community-based survey was
      conducted for severe childhood disability using the Key Informants Method between
      September 2011 and March 2012 in a rural sub-district of Bangladesh. RESULTS: We
      screened 1069 children and identified 859 with severe disabilities. The mean age
      of the disabled children was 8.5 year and 42.9% were girls. The major forms of
      impairments/conditions were cerebral palsy (n = 324, 37.7%), hearing impairment
      (n = 201, 23.4%), physical impairment (n = 147, 17.1%), visual impairment (n =
      49, 5.7%), cerebral palsy with epilepsy (n = 39, 4.5%) and epilepsy (n = 41,
      4.7%). Congenital rubella syndrome was identified in 1.1% (n = 9). 7.1%
      disabilities resulted from clinically confirmed infections, and another 10.8%
      originated from probable infections; thus a total of 17.9% disabilities were
      related to an infectious origin. CONCLUSIONS: Infectious diseases appear to be
      one of the major causes of severe childhood disability in rural Bangladesh.

PMID- 24929077
TI  - Re: Matching tumor risk with aggressiveness of treatment in men with multiple
      comorbidities and early-stage prostate cancer.

PMID- 24929078
TI  - Re: Architectural heterogeneity and cribriform pattern predict adverse clinical
      outcome for Gleason grade 4 prostatic adenocarcinoma.

PMID- 24929079
TI  - Re: Metformin use and all-cause and prostate cancer-specific mortality among men
      with diabetes.

PMID- 24929080
TI  - Re: Increased risk of non-fatal myocardial infarction following testosterone
      therapy prescription in men.

PMID- 24929081
TI  - Re: Global effects of smoking, of quitting, and of taxing tobacco.

PMID- 24929082
TI  - Re: Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta
      analysis.

PMID- 24929083
TI  - TESTIN suppresses tumor growth and invasion via manipulating cell cycle
      progression in endometrial carcinoma.
AB  - BACKGROUND: The TESTIN gene was demonstrated to be a tumor suppressor in prostate
      and breast cancer through inhibiting tumor growth and invasion. Herein, we aimed
      to investigate the detailed functions of TESTIN in the highly sexual hormone
      (estrogen)-dependent malignancy, endometrial carcinoma. MATERIAL AND METHODS:
      TESTIN mRNA and protein expression were measured by qRT-PCR, Western blot and
      immunohistochemistry. Upregulation of TESTIN was achieved by transfecting the
      pcDNA3.1-TESTIN plasmids into AN3CA cells. Knockdown of TESTIN was achieved by
      transfecting the shRNA-TESTIN into Ishikawa cells. MTT assay, colony formation
      assay, and Transwell assay were used to investigate the effects of TESTIN on
      cellular proliferation and invasion. The apoptotic status and cell cycle were
      analyzed using flow cytometry. MMP2 secretion was determined by ELISA assay. The
      xenograft assay was used to investigate the functions of TESTIN in nude mice.
      RESULTS: Compared to the non-malignant adjacent endometrium, 54% of tumor samples
      presented downregulation of TESTIN (P<0.001). Loss of TESTIN protein was
      correlated with advanced tumor stage (P=0.047), high grade (P=0.034), and
      lymphatic vascular space invasion (P=0.036). In vitro, overexpression of TESTIN
      suppressed cell proliferation, induced dramatic G1 arrest, and inhibited tumor
      invasion through blocking the secretion of MMP2. Loss of TESTIN accelerated
      cellular proliferation, promoted cell cycle progression, and enhanced tumor
      invasion by increasing the secretion of MMP2. Consistently, TESTIN could
      significantly delay the growth of xenografts in nude mice. CONCLUSIONS: TESTIN
      was commonly downregulated in human endometrial carcinoma and was associated with
      poor prognostic markers. Moreover, TESTIN significantly inhibited tumor growth
      and invasion via arresting cell cycle in in vitro and in vivo experiments.
      Therefore, we propose that TESTIN might be a prognostic marker and therapeutic
      target for endometrial carcinoma.

PMID- 24929084
TI  - Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against
      chikungunya virus.
AB  - Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the
      available treatment strategies can only alleviate disease symptoms, and no
      effective therapeutics or vaccines are currently available for human use. Here,
      we report the use of a new cost-effective approach involving production of a
      recombinant antiviral peptide-fusion protein that is scalable for the treatment
      of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was
      generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1
      antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was
      produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN
      protein showed 89.0% reduction of viral plaque formation compared with PAP1
      (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein
      reduced the viral RNA load that was 0.89-fold compared with the untreated control
      cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and
      LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1
      THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of
      11.2MUg/ml, which is approximately half of the EC50 of PAP1 (23.7MUg/ml) and
      protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that
      production of antiviral peptide-fusion protein in E. coli as inclusion bodies
      could accentuate antiviral activities, enhance cellular internalisation, and
      could reduce product toxicity to host cells and is scalable to epidemic response
      quantities. 

PMID- 24929085
TI  - DNA-dependent RNA polymerase detects hidden giant viruses in published databanks.
AB  - Environmental metagenomic studies show that there is a "dark matter," composed of
      sequences not linked to any known organism, as determined mainly using ribosomal
      DNA (rDNA) sequences, which therefore ignore giant viruses. DNA-dependent RNA
      polymerase (RNAP) genes are universal in microbes and conserved in giant viruses
      and may replace rDNA for identifying microbes. We found while reconstructing RNAP
      subunit 2 (RNAP2) phylogeny that a giant virus sequenced together with the genome
      of a large eukaryote, Hydra magnipapillata, has been overlooked. To explore the
      dark matter, we used viral RNAP2 and reconstructed putative ancestral RNAP2,
      which were significantly superior in detecting distant clades than current
      sequences, and we revealed two additional unknown mimiviruses, misclassified as
      an euryarchaeote and an oomycete plant pathogen, and detected unknown putative
      viral clades. We suggest using RNAP systematically to decipher the black matter
      and identify giant viruses. 

PMID- 24929086
TI  - Optimal detection of cholinesterase activity in biological samples: modifications
      to the standard Ellman's assay.
AB  - Ellman's assay is the most commonly used method to measure cholinesterase
      activity. It is cheap, fast, and reliable, but it has limitations when used for
      biological samples. The problems arise from 5,5-dithiobis(2-nitrobenzoic acid)
      (DTNB), which is unstable, interacts with free sulfhydryl groups in the sample,
      and may affect cholinesterase activity. We report that DTNB is more stable in
      0.09 M Hepes with 0.05 M sodium phosphate buffer than in 0.1M sodium phosphate
      buffer, thereby notably reducing background. Using enzyme-linked immunosorbent
      assay (ELISA) to enrich tissue homogenates for cholinesterase while depleting the
      sample of sulfhydryl groups eliminates unwanted interactions with DTNB, making it
      possible to measure low cholinesterase activity in biological samples. To
      eliminate possible interference of DTNB with enzyme hydrolysis, we introduce a
      modification of the standard Ellman's assay. First, thioesters are hydrolyzed by
      cholinesterase to produce thiocholine in the absence of DTNB. Then, the reaction
      is stopped by a cholinesterase inhibitor and the produced thiocholine is revealed
      by DTNB and quantified at 412 nm. Indeed, this modification of Ellman's method
      increases butyrylcholinesterase activity by 20 to 25%. Moreover, high stability
      of thiocholine enables separation of the two reactions of the Ellman's method
      into two successive steps that may be convenient for some applications.

PMID- 24929087
TI  - Quantitative pH assessment of small-volume samples using a universal pH
      indicator.
AB  - We developed a hue-based pH determination method to analyze digital images of
      samples in a 384-well plate after the addition of a universal pH indicator. The
      standard error of calibration for 69 pH standards was 0.078 pH units, and no
      sample gave an error greater than 0.23 units. We then used in-solution
      isoelectric focusing to determine the isoelectric point of Wnt3A protein in
      conditioned medium and after purification and applied the described method to
      assess the pH of these small-volume samples. End users may access our standard to
      assay the pH of their own samples with no additional calibration. 

PMID- 24929088
TI  - Short homologies efficiently generate detectable homologous recombination events.
AB  - When recombineering bacterial artificial chromosomes (BACs), it is common
      practice to design the ends of the donor molecule with 50 bp of homology
      specifying its insertion site. We demonstrate that desired recombinants can be
      produced using intermolecular homologies as short as 15 bp. Although the use of
      shorter donor end regions decreases total recombinants by several fold, the
      frequency of recombinants with correctly inserted donor molecules was high enough
      for easy detection by simple polymerase chain reaction (PCR) screening. This
      observation may have important implications for the design of oligonucleotides
      for recombineering, including significant cost savings, especially for high
      throughput projects that use large quantities of primers.

PMID- 24929089
TI  - High-throughput amplification of mature microRNAs in uncharacterized animal
      models using polyadenylated RNA and stem-loop reverse transcription polymerase
      chain reaction.
AB  - This study makes a significant advancement on a microRNA amplification technique
      previously used for expression analysis and sequencing in animal models without
      annotated mature microRNA sequences. As research progresses into the post-genomic
      era of microRNA prediction and analysis, the need for a rapid and cost-effective
      method for microRNA amplification is critical to facilitate wide-scale analysis
      of microRNA expression. To facilitate this requirement, we have reoptimized the
      design of amplification primers and introduced a polyadenylation step to allow
      amplification of all mature microRNAs from a single RNA sample. Importantly, this
      method retains the ability to sequence reverse transcription polymerase chain
      reaction (RT-PCR) products, validating microRNA-specific amplification. 

PMID- 24929090
TI  - Liver sinusoidal cells collecting MHC-I molecules: you can't get enough of a good
      thing.

PMID- 24929091
TI  - IFNL3 expression and response to treatment: behind the HCV tricks.

PMID- 24929093
TI  - Stones, sugar and air-emphysematous pyelonephritis.

PMID- 24929092
TI  - Reply to: "bacterial translocation in liver cirrhosis: site and role in
      fibrogenesis".

PMID- 24929094
TI  - Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast
      cancer cells co-cultured with breast adipose fibroblasts.
AB  - Targeting the estrogen pathway has been proven effective in the treatment for
      estrogen receptor positive breast cancer. There are currently two common groups
      of anti-estrogenic compounds used in the clinic; Selective Estrogen Receptor
      Modulators (SERMs, e.g. tamoxifen) and Selective Estrogen Enzyme Modulators
      (SEEMs e.g. letrozole). Among various naturally occurring, biologically active
      compounds, resveratrol and melatonin have been suggested to act as aromatase
      inhibitors, which make them potential candidates in hormonal treatment of breast
      cancer. Here we used a co-culture model in which we previously demonstrated that
      primary human breast adipose fibroblasts (BAFs) can convert testosterone to
      estradiol, which subsequently results in estrogen receptor-mediated breast cancer
      T47D cell proliferation. In the presence of testosterone in this model, we
      examined the effect of letrozole, resveratrol and melatonin on cell
      proliferation, estradiol (E2) production and gene expression of CYP19A1, pS2 and
      Ki-67. Both melatonin and resveratrol were found to be aromatase inhibitors in
      this co-culture system, albeit at different concentrations. Our co-culture model
      did not provide any indications that melatonin is also a selective estrogen
      receptor modulator. In the T47D-BAF co-culture, a melatonin concentration of 20
      nM and resveratrol concentration of 20 MUM have an aromatase inhibitory effect as
      potent as 20 nM letrozole, which is a clinically used anti-aromatase drug in
      breast cancer treatment. The SEEM mechanism of action of especially melatonin
      clearly offers potential advantages for breast cancer treatment.

PMID- 24929095
TI  - CYP2E1 induction leads to oxidative stress and cytotoxicity in glutathione
      depleted cerebellar granule neurons.
AB  - Increasing evidence suggests that brain cytochrome P450 (CYP) can contribute to
      the in situ metabolism of xenobiotics. In the liver, some xenobiotics can be
      metabolized by CYPs into more reactive products that can damage hepatocytes and
      induce cell death. In addition, normal CYP activity may produce reactive oxygen
      species (ROS) that contribute to cell damage through oxidative mechanisms. CYP2E1
      is a CYP isoform that can generate ROS leading to cytotoxicity in multiple tissue
      types. The aim of this study was to determine whether CYP2E1 induction may lead
      to significant brain cell impairment. Immunological analysis revealed that
      exposure of primary cerebellar granule neuronal cultures to the CYP inducer
      isoniazid, increased CYP2E1 expression. In the presence of buthionine
      sulfoximine, an agent that reduces glutathione levels, isoniazid treatment also
      resulted in reactive oxygen species (ROS) production, DNA oxidation and cell
      death. These effects were attenuated by simultaneous exposure to diallyl sulfide,
      a CYP2E1 inhibitor, or to a mimetic of superoxide dismutase/catalase, (Euka).
      These results suggest that in cases of reduced antioxidant levels, the induction
      of brain CYP2E1 could represent a risk of in situ neuronal damage.

PMID- 24929096
TI  - Integration of pharmacokinetic and NRF2 system biology models to describe
      reactive oxygen species production and subsequent glutathione depletion in liver
      microfluidic biochips after flutamide exposure.
AB  - We present a systems biology analysis of rat primary hepatocytes response after
      exposure to 10 MUM and 100 MUM flutamide in liver microfluidic biochips. We
      coupled an in vitro pharmacokinetic (PK) model of flutamide to a system biology
      model of its reactive oxygen species (ROS) production and scavenging by the Nrf2
      regulated glutathione production. The PK model was calibrated using data on
      flutamide kinetics, hydroxyflutamide and glutathione conjugates formation in
      microfluidic conditions. The parameters of Nrf2-related gene activities and the
      subsequent glutathione depletion were calibrated using microarray data from our
      microfluidic experiments and literature information. Following a 10 MUM flutamide
      exposure, the model predicted a recovery time to baseline levels of glutathione
      (GSH) and ROS in agreement with our experimental observations. At 100 MUM, the
      model predicted that metabolism saturation led to an important accumulation of
      flutamide in cells, a high ROS production and complete GSH depletion. The high
      levels of ROS predicted were consistent with the necrotic switch observed by
      transcriptomics, and the high cell mortality we had experimentally observed. The
      model predicted a transition between recoverable GSH depletion and deep GSH
      depletion at about 12.5 MUM of flutamide (single perfusion exposure). Our work
      shows that in vitro biochip experiments can provide supporting information for
      complex in silico modeling including data from extra cellular and intra cellular
      levels. We believe that this approach can be an efficient strategy for a global
      integrated methodology in predictive toxicology.

PMID- 24929097
TI  - Diagnostic accuracy of the WHO clinical staging system for defining eligibility
      for ART in sub-Saharan Africa: a systematic review and meta-analysis.
AB  - INTRODUCTION: The World Health Organization (WHO) recommends that HIV-positive
      adults with CD4 count <=500 cells/mm(3) initiate antiretroviral therapy (ART). In
      many countries of sub-Saharan Africa, CD4 count is not widely available or
      consistently used and instead the WHO clinical staging system is used to
      determine ART eligibility. However, concerns have been raised regarding its
      discriminatory ability to identify patients eligible to start ART. We therefore
      reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART
      eligibility according to CD4 count thresholds for ART initiation. METHODS: We
      systematically searched PubMed and Global Health databases and conference
      abstracts using a comprehensive strategy for studies that compared the results of
      WHO clinical staging with CD4 count thresholds. Studies performed in sub-Saharan
      Africa and published in English between 1998 and 2013 were eligible for inclusion
      according to our predefined study protocol. Two authors independently extracted
      data and assessed methodological quality and risk of bias using the Quality
      Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Summary
      estimates of sensitivity and specificity were derived for each CD4 count
      threshold and hierarchical summary receiver operator characteristic curves were
      plotted. RESULTS: Fifteen studies met the inclusion criteria, including 25,032
      participants from 14 countries. Most studies assessed individuals attending ART
      clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a
      sensitivity of 60% (95% CI: 45-73%, Q=914.26, p<0.001) and specificity of 73%
      (95% CI: 60-83%, Q=1439.43, p<0.001) for a CD4 threshold of <=200 cells/mm(3) (11
      studies); sensitivity and specificity for a threshold of CD4 count <=350
      cells/mm(3) were 45% (95% CI: 26-66%, Q=1607.31, p<0.001) and 85% (95% CI: 69
      93%, Q=896.70, p<0.001), respectively (six studies). For the threshold of CD4
      count <=500 cells/mm(3) sensitivity was 14% (95% CI: 13-15%) and specificity was
      95% (95% CI: 94-96%) (one study). CONCLUSIONS: When used for individual treatment
      decisions, WHO clinical staging misses a high proportion of individuals who are
      ART eligible by CD4 count, with sensitivity falling as CD4 count criteria rises.
      Access to accurate, accessible, robust and affordable CD4 count testing methods
      will be a pressing need for as long as ART initiation decisions are based on
      criteria other than seropositivity.

PMID- 24929100
TI  - Prediction of bacterial protein subcellular localization by incorporating various
      features into Chou's PseAAC and a backward feature selection approach.
AB  - Information on the subcellular localization of bacterial proteins is essential
      for protein function prediction, genome annotation and drug design. Here we
      proposed a novel approach to predict the subcellular localization of bacterial
      proteins by fusing features from position-specific score matrix (PSSM), Gene
      Ontology (GO) and PROFEAT. A backward feature selection approach by linear kennel
      of SVM was then used to rank the integrated feature vectors and extract optimal
      features. Finally, SVM was applied for predicting protein subcellular locations
      based on these optimal features. To validate the performance of our method, we
      employed jackknife cross-validation tests on three low similarity datasets, i.e.,
      M638, Gneg1456 and Gpos523. The overall accuracies of 94.98%, 93.21%, and 94.57%
      were achieved for these three datasets, which are higher (from 1.8% to 10.9%)
      than those by state-of-the-art tools. Comparison results suggest that our method
      could serve as a very useful vehicle for expediting the prediction of bacterial
      protein subcellular localization. 

PMID- 24929101
TI  - Unusual carboxylesterase bearing a GGG(A)X-type oxyanion hole discovered in
      Paenibacillus barcinonensis BP-23.
AB  - Strain Paenibacillus barcinonensis BP-23, previously isolated from Ebro's river
      delta (Spain), bears a complex hydrolytic system showing the presence of at least
      two enzymes with activity on lipidic substrates. EstA, a cell-bound B-type
      carboxylesterase from the strain was previously isolated and characterized. The
      gene coding for a second putative lipase, located upstream cellulase Cel5A, was
      obtained using a genome walking strategy and cloned in Escherichia coli for
      further characterization. The recombinant clone obtained displayed high activity
      on medium/short-chain fatty acid-derivative substrates. The enzyme, named Est23,
      was purified and characterized, showing maximum activity on pNP-caprylate (C8:0)
      or MUF-heptanoate (C7:0) under conditions of moderate temperature and pH.
      Although Est23 displays a GGG(A)X-type oxyanion hole, described as an important
      motif for tertiary alcohol ester resolution, neither conversion nor enantiomeric
      resolution of tertiary alcohols could be detected. Amino acid sequence alignment
      of Est23 with those of known bacterial lipase families and with closely related
      proteins suggests that the cloned enzyme does not belong to any of the described
      bacterial lipase families. A phylogenetic tree including Est23 and similar amino
      acid sequences showed that the enzyme belongs to a differentiated sequence
      cluster which probably constitutes a new family of bacterial lipolytic enzymes. 

PMID- 24929102
TI  - Impairment of interstrain social recognition during territorial aggressive
      behavior in oxytocin receptor-null mice.
AB  - In humans, oxytocin has been shown to be involved in in-group cooperative
      behaviors and out-group aggression. Studies have also demonstrated that oxytocin
      plays a pivotal role in social recognition. However, no empirical research has
      investigated the effect of oxytocin on in-group and out-group aggressiveness. We
      employed a resident-intruder paradigm to assess the ability of resident male mice
      to discriminate intruder male strain differences. We found that resident male
      mice exhibited higher frequencies of attack bites against intruders of different
      strains than against intruders of their own strain. Subsequently, we examined
      whether the interstrain recognition was regulated by the oxytocin system using
      oxytocin receptor (OTR)-null mice. OTR wild-type or heterozygous residents
      displayed higher aggression toward intruders of a strain different from their own
      (C57BL/6J). On the other hand, OTR-null residents exhibited greater aggression
      toward intruders of the same strain compared to OTR wild-type or heterozygous
      residents, and aggression levels were not different compared to those exhibited
      toward other strains. Our findings demonstrated that the oxytocin system
      contributes to interstrain social recognition in territorial aggression in male
      mice, implying that one function of oxytocin is to promote an in-group "tend-and
      defend" response, such as in-group favoritism, which could be evolutionarily
      conserved in mammals. 

PMID- 24929098
TI  - The regulation of reproductive neuroendocrine function by insulin and insulin
      like growth factor-1 (IGF-1).
AB  - The mammalian reproductive hormone axis regulates gonadal steroid hormone levels
      and gonadal function essential for reproduction. The neuroendocrine control of
      the axis integrates signals from a wide array of inputs. The regulatory pathways
      important for mediating these inputs have been the subject of numerous studies.
      One class of proteins that have been shown to mediate metabolic and growth
      signals to the CNS includes Insulin and IGF-1. These proteins are structurally
      related and can exert endocrine and growth factor like action via related
      receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling
      the hypothalamus and pituitary and their role in regulating puberty and
      nutritional control of reproduction has been studied extensively. This review
      summarizes the in vitro and in vivo models that have been used to study these
      neuroendocrine structures and the influence of these growth factors on
      neuroendocrine control of reproduction. 

PMID- 24929103
TI  - Involvement of P38MAPK activation by NMDA receptors and non-NMDA receptors in
      amyloid-beta peptide-induced neuronal loss in rat hippocampal CA1 and CA3
      subfields.
AB  - Oligomeric amyloid-beta peptide (Abeta) has been found to be associated with the
      pathogenesis of Alzheimer's disease (AD). Numerous studies have reported Abeta
      neurotoxicity, but the underlying molecular mechanisms remain to be fully
      illuminated. In the present study, we investigated the Abeta-induced activation
      and regulation of P38MAPKs in rat hippocampus in vivo. The results showed that
      intracerebroventricular injection of oligomeric Abeta25-35 increased the
      activation (phosphorylation) of P38MAPKs, and the level of cleaved caspase-3, but
      decreased the number of neurons in rat hippocampal CA1 and CA3 subfields.
      Downregulation of P38MAPK activity by SB239063 protected against the Abeta
      neurotoxicity. Pretreatment with NMDA and non-NMDA receptor antagonists
      respectively suppressed P38MAPK activation induced by Abeta25-35 oligomers and
      presented neuroprotective effect. Taken together, these data suggest that P38MAPK
      activation via NMDA and non-NMDA receptors is a key signal cascade in Abeta
      induced neuronal death. Inhibition of P38MAPK cascades may be a promising
      treatment in AD. 

PMID- 24929104
TI  - Role of the red nucleus in suppressing the jaw-opening reflex following
      stimulation of the raphe magnus nucleus.
AB  - In a previous study, we found that electrical and chemical stimulation of the red
      nucleus (RN) suppressed the high-threshold afferent-evoked jaw-opening reflex
      (JOR). It has been reported that the RN receives bilaterally projection fibers
      from the raphe magnus nucleus (RMg), and that stimulation of the RMg inhibits the
      tooth pulp-evoked nociceptive JOR. These facts imply that RMg-induced inhibition
      of the JOR could be mediated via the RN. The present study first examines whether
      stimulation of the RMg suppresses the high-threshold afferent-evoked JOR. The JOR
      was evoked by electrical stimulation of the inferior alveolar nerve (IAN), and
      was recorded as the electromyographic response of the anterior belly of the
      digastric muscle. The stimulus intensity was 4.0 (high-threshold) times the
      threshold. Conditioning electrical stimulation of the RMg significantly
      suppressed the JOR. A further study then examined whether electrically induced
      lesions of the RN or microinjection of muscimol into the RN affects RMg-induced
      suppression of the JOR. Electrically induced lesions of the bilateral RN and
      microinjection of muscimol into the bilateral RN both reduced the RMg-induced
      suppression of the JOR. These results suggest that RMg-induced suppression of the
      high-threshold afferent-evoked JOR is mediated by a relay in the RN. 

PMID- 24929105
TI  - Coptis chinensis Franch. exhibits neuroprotective properties against oxidative
      stress in human neuroblastoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizome of Coptis chinensis Franch.
      (family Ranunculaceae) is traditionally used in Chinese medicine for the
      treatment of inflammatory diseases and diabetes. Recent studies showed a variety
      of activities of Coptis chinensis Franch. alkaloids, including neuroprotective,
      neuroregenerative, anti-diabetic, anti-oxidative and anti-inflammatory effects.
      However, there is no report on the neuroprotective effect of Coptis chinensis
      Franch. watery extract against tert-butylhydroperoxide (t-BOOH) induced oxidative
      damage. The aim of the study is to investigate neuroprotective properties of
      Coptis chinensis Franch. rhizome watery extract (CRE) and to evaluate its
      potential mechanism of action. MATERIALS AND METHODS: Neuroprotective properties
      on t-BOOH induced oxidative stress were investigated in SH-SY5Y human
      neuroblastoma cells. Cells were pretreated with CRE for 2 h or 24 h followed by 2
      h of treatment with t-BOOH. To evaluate the neuroprotective effect of CRE, cell
      viability, cellular reactive oxygen species (ROS), mitochondrial membrane
      potential (MMP) and the apoptotic rate were determined and microarray analyses,
      as well as qRT-PCR analyses were conducted. RESULTS: Two hours of exposure to 100
      uM t-BOOH resulted in a significant reduction of cell viability, increased
      apoptotic rate, declined mitochondrial membrane potential (MMP) and increased ROS
      production. Reduction of cell viability, increased apoptotic rate and declined
      mitochondrial membrane potential (MMP) could be significantly reduced in cells
      pretreated with CRE (100 ug/ml) for 2h or 24h ahead of t-BOOH exposure with the
      greatest effect after 24h of pretreatment; however ROS production was not changed
      significantly. Furthermore, microarray analyses revealed that the expressions of
      2 genes; thioredoxin-interacting protein (TXNIP) and mitochondrially encoded NADH
      dehydrogenase 1, were significantly regulated. Down regulation of TXNIP was
      confirmed by qRT-PCR. CONCLUSION: Due to its neuroprotective properties CRE might
      be a potential therapeutic agent for the prevention or amelioration of diseases
      like diabetic neuropathy and neurodegenerative disorders like Alzheimer and
      Parkinsons disease.

PMID- 24929099
TI  - GABAA receptor-acting neurosteroids: a role in the development and regulation of
      the stress response.
AB  - Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress
      is a fundamental survival mechanism and HPA-dysfunction is implicated in
      psychiatric disorders. Adverse early life experiences, e.g. poor maternal care,
      negatively influence brain development and programs an abnormal stress response
      by encoding long-lasting molecular changes, which may extend to the next
      generation. How HPA-dysfunction leads to the development of affective disorders
      is complex, but may involve GABAA receptors (GABAARs), as they curtail stress
      induced HPA axis activation. Of particular interest are endogenous neurosteroids
      that potently modulate the function of GABAARs and exhibit stress-protective
      properties. Importantly, neurosteroid levels rise rapidly during acute stress,
      are perturbed in chronic stress and are implicated in the behavioural changes
      associated with early-life adversity. We will appraise how GABAAR-active
      neurosteroids may impact on HPA axis development and the orchestration of the
      stress-evoked response. The significance of these actions will be discussed in
      the context of stress-associated mood disorders. 

PMID- 24929106
TI  - Cytotoxicity and inhibition of P-glycoprotein by selected medicinal plants from
      Thailand.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Thai medicine has a long tradition of tonifying
      medicinal plants. In the present investigation, we studied the flower extracts of
      Jasminum sambac, Mammea siamensis, Mesua ferrea, Michelia alba, Mimusops elengi,
      and Nelumbo nucifera and speculated that these plants might influence metabolism
      and substance flow in the body. MATERIALS AND METHODS: Isolation of porcine brain
      capillary endothelial cells (PBCECs) as well as multidrug-resistance CEM/ADR5000
      leukemia cells, MDA-M;B-231 breast cancer, U-251 brain tumor, and HCT-116 colon
      cancer cells were used. The calcein-acetoxymethylester (AM) assay was used to
      measure inhibition of P-glycoprotein transport. XTT and resazurin assays served
      for measuring cytotoxicity. RESULTS: The extracts revealed cytotoxicity towards
      CCRF-CEM leukemia cells to a different extent. The strongest growth inhibition
      was found for the n-hexane extracts of Mammea siamensis and Mesua ferrea, and the
      dichloromethane extracts of Mesua ferrea and Michelia alba. The flower extracts
      also inhibited P-glycoprotein function in porcine brain capillary endothelial
      cells and CEM/ADR5000 leukemia cells, indicating modulation of the blood-brain
      barrier and multidrug resistance of tumors. Bioactivity-guided isolation of
      coumarins from Mammea siamensis flowers revealed considerable cytotoxicity of
      mammea A/AA, deacetylmammea E/BA and deacetylmammea E/BB towards human MDA-MB-231
      breast cancer, U-251 brain tumor, HCT-116 colon cancer, and CCRF-CEM leukemia
      cells. CONCLUSION: The plants analyzed may be valuable in developing novel
      treatment strategies to overcome the blood-brain barrier and multidrug-resistance
      in tumor cells mediated by P-glycoprotein.

PMID- 24929107
TI  - Pharmacokinetic comparisons of five ephedrine alkaloids following oral
      administration of four different Mahuang-Guizhi herb-pair aqueous extracts ratios
      in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Herba Ephedra (Mahuang in Chinese), is derived
      from dried Ephedra sinica Stapf stems and has been widely used to treat the
      common cold, coughs, asthma, and edema for thousands of years. The Mahuang-Guizhi
      herb-pair is a famous formula composed of Mahuang and Ramulus Cinnamomi (Guizhi
      in Chinese, the dried twig of Cinnamomum cassia Presl.), used to improve
      pharmacological effects and reduce toxicity. In order to investigate the
      influence of Mahuang-Guizhi herb-pair ratios on bioavailability, the plasma
      pharmacokinetics profiles of five ephedrine alkaloids were compared following
      oral administration of four different ratios to rats. MATERIALS AND METHODS:
      Sprague-Dawley rats were randomly assigned to four groups and orally administered
      Mahuang-Guizhi (ratios 3:0; 3:1; 3:2; 3:4, w/w). Assays for five ephedrine
      alkaloids (ephedrine, pseudoephedrine, methylephedrine, norephedrine, and
      norpseudoephedrine) were developed and validated using ultra-high-performance
      liquid chromatography tandem mass spectrometry coupled with liquid-liquid
      extraction. RESULTS: Key pharmacokinetic parameters of the five ephedrine
      alkaloids (maximal plasma concentration, mean residence time, and half-life) were
      significantly different (p<0.05) after oral administration of Mahuang-Guizhi herb
      pair ratios, as compared to those of Mahuang. CONCLUSION: Ephedrine alkaloid
      pharmacokinetic differences in rat plasma could help explain previous findings of
      pharmacological and toxicity differences between Mahuang and Mahuang-Guizhi herb
      pair preparations. These results could facilitate future studies to increase the
      efficacy and decrease the toxicity of Mahuang and Guizhi.

PMID- 24929108
TI  - The use of plants in the traditional management of diabetes in Nigeria:
      pharmacological and toxicological considerations.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of diabetes is on a steady
      increase worldwide and it is now identified as one of the main threats to human
      health in the 21st century. In Nigeria, the use of herbal medicine alone or
      alongside prescription drugs for its management is quite common. We hereby carry
      out a review of medicinal plants traditionally used for diabetes management in
      Nigeria. Based on the available evidence on the species' pharmacology and safety,
      we highlight ways in which their therapeutic potential can be properly harnessed
      for possible integration into the country's healthcare system. MATERIALS AND
      METHODS: Ethnobotanical information was obtained from a literature search of
      electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for
      publications on medicinal plants used in diabetes management, in which the place
      of use and/or sample collection was identified as Nigeria. 'Diabetes' and
      'Nigeria' were used as keywords for the primary searches; and then 'Plant name -
      accepted or synonyms', 'Constituents', 'Drug interaction' and/or 'Toxicity' for
      the secondary searches. RESULTS: The hypoglycemic effect of over a hundred out of
      the 115 plants reviewed in this paper is backed by preclinical experimental
      evidence, either in vivo or in vitro. One-third of the plants have been studied
      for their mechanism of action, while isolation of the bioactive constituent(s)
      has been accomplished for twenty three plants. Some plants showed specific organ
      toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of
      some liver function enzymes. Twenty eight plants have been identified as in vitro
      modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes,
      while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly
      glutathione, with the potential to alter the pharmacokinetics of co-administered
      drugs. CONCLUSION: This review, therefore, provides a useful resource to enable a
      thorough assessment of the profile of plants used in diabetes management so as to
      ensure a more rational use. By anticipating potential toxicities or possible herb
      drug interactions, significant risks which would otherwise represent a burden on
      the country's healthcare system can be avoided.

PMID- 24929109
TI  - Alcohol: a stimulant activating brain stress responsive systems with persistent
      neuroadaptation.
AB  - Addictive diseases, including addiction to alcohol, opiates or cocaine, pose
      massive public health costs. Addictions are chronic relapsing brain diseases,
      caused by drug-induced direct effects and persistent neuroadaptations at the
      molecular, cellular and behavioral levels. These drug-type specific
      neuroadapations are mainly contributed by three factors: environment, including
      stress, the direct reinforcing effects of the drug on the CNS, and genetics.
      Results from animal models and basic clinical research (including human genetic
      study) have shown important interactions between the stress responsive systems
      and alcohol abuse. In this review we will discuss the involvement of the
      dysregulation of the stress responsive hypothalamic-pituitary-adrenal (HPA) axis
      in alcohol addiction (Section I). Addictions to specific drugs such as alcohol,
      psychostimulants and opiates (e.g., heroin) have some common direct or downstream
      effects on several brain stress-responsive systems, including vasopressin and its
      receptor system (Section II), POMC and mu opioid receptor system (Section III)
      and dynorphin and kappa opioid receptor systems (Section IV). Further
      understanding of these systems, through laboratory-based and translational
      studies, have the potential to optimize early interventions and to discover new
      treatment targets for the therapy of alcoholism. This article is part of the
      Special Issue entitled 'CNS Stimulants'. 

PMID- 24929110
TI  - Activation of neurotensin receptor type 1 attenuates locomotor activity.
AB  - Intracerebroventricular administration of neurotensin (NT) suppresses locomotor
      activity. However, the brain regions that mediate the locomotor depressant effect
      of NT and receptor subtype-specific mechanisms involved are unclear. Using a
      brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we
      investigated the effect of systemic and brain region-specific NTS1 activation on
      locomotor activity. Systemic administration of PD149163 attenuated the locomotor
      activity of C57BL/6J mice both in a novel environment and in their homecage.
      However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1
      mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined
      whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment
      with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8
      mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)
      induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the
      nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated
      in the behavioral effects of NT, we examined whether microinjection of PD149163
      into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into
      the NAc, but not the mPFC suppressed locomotor activity. In summary, our results
      indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce
      locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study
      will be helpful to identify pharmacological factors and a possible therapeutic
      window for NTS1-targeted therapies for movement disorders. 

PMID- 24929111
TI  - Effects of D-series resolvins on behavioral and neurochemical changes in a
      fibromyalgia-like model in mice.
AB  - This study investigated whether the spinal or systemic treatment with the lipid
      resolution mediators resolvin D1 (RvD1), aspirin-triggered resolvin D1 (AT-RvD1)
      and resolvin D2 (RvD2) might interfere with behavioral and neurochemical changes
      in the mouse fibromyalgia-like model induced by reserpine. Acute administration
      of AT-RvD1 and RvD2 produced a significant inhibition of mechanical allodynia and
      thermal sensitization in reserpine-treated mice, whereas RvD1 was devoid of
      effects. A similar antinociceptive effect was obtained by acutely treating
      animals with the reference drug pregabalin. Noteworthy, the repeated
      administration of AT-RvD1 and RvD2 also prevented the depressive-like behavior in
      reserpine-treated animals, according to assessment of immobility time, although
      the chronic administration of pregabalin failed to affect this parameter. The
      induction of fibromyalgia by reserpine triggered a marked decrease of dopamine
      and serotonin (5-HT) levels, as examined in total brain, spinal cord, cortex and
      thalamus. Reserpine also elicited a reduction of glutamate levels in total brain,
      and a significant increase in the spinal cord and thalamus. Chronic treatment
      with RvD2 prevented 5-HT reduction in total brain, and reversed the glutamate
      increases in total brain and spinal cord. Otherwise, AT-RvD1 led to a recovery of
      dopamine levels in cortex, and 5-HT in thalamus, whilst it diminished brain
      glutamate contents. Concerning pregabalin, this drug prevented dopamine reduction
      in total brain, and inhibited glutamate increase in brain and spinal cord of
      reserpine-treated animals. Our data provide novel evidence, showing the ability
      of D-series resolvins AT-RvD1, and mainly RvD2, in reducing painful and
      depressive symptoms allied to fibromyalgia in mice. 

PMID- 24929113
TI  - Morphofunctional characterization of decellularized vena cava as tissue
      engineering scaffolds.
AB  - Clinical experience for peripheral arterial disease treatment shows poor results
      when synthetic grafts are used to approach infrapopliteal arterial segments.
      However, tissue engineering may be an option to yield surrogate biocompatible
      neovessels. Thus, biological decellularized scaffolds could provide natural
      tissue architecture to use in tissue engineering, when the absence of ideal
      autologous veins reduces surgical options. The goal of this study was to evaluate
      different chemical induced decellularization protocols of the inferior vena cava
      of rabbits. They were decellularized with Triton X100 (TX100), sodium dodecyl
      sulfate (SDS) or sodium deoxycholate (DS). Afterwards, we assessed the remaining
      extracellular matrix (ECM) integrity, residual toxicity and the biomechanical
      resistance of the scaffolds. Our results showed that TX100 was not effective to
      remove the cells, while protocols using SDS 1% for 2h and DS 2% for 1h,
      efficiently removed the cells and were better characterized. These scaffolds
      preserved the original organization of ECM. In addition, the residual toxicity
      assessment did not reveal statistically significant changes while decellularized
      scaffolds retained the equivalent biomechanical properties when compared with the
      control. Our results concluded that protocols using SDS and DS were effective at
      obtaining decellularized scaffolds, which may be useful for blood vessel tissue
      engineering. 

PMID- 24929112
TI  - SKF-83959 is not a highly-biased functionally selective D1 dopamine receptor
      ligand with activity at phospholipase C.
AB  - SKF-83959 [6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro
      1H-3-benzazepine] is reported to be a functionally selective dopamine D1 receptor
      ligand with high bias for D1-mediated phospholipase C (PLC) versus D1-coupled
      adenylate cyclase signaling. This signaling bias is proposed to explain
      behavioral activity in both rat and primate Parkinson's disease models, and a D1
      D2 heterodimer has been proposed as the underlying mechanism. We have conducted
      an in-depth pharmacological characterization of this compound in dopamine D1 and
      D2 receptors in both rat brain and heterologous systems expressing human D1 or D2
      receptors. Contrary to common assumptions, SKF-83959 is similar to the classical,
      well-characterized partial agonist SKF38393 in all systems. It is a partial
      agonist (not an antagonist) at adenylate cyclase in vitro and ex vivo, and is a
      partial agonist in D1-mediated beta-arrestin recruitment. Contrary to earlier
      reports, it does not have D1-mediated effects on PLC signaling in heterologous
      systems. Because drug metabolites can also contribute, its 3-N-demethylated
      analog also was synthesized and tested. As expected from the known structure
      activity relationships of the benzazepines, this compound also had high affinity
      for the D1 receptor and somewhat higher intrinsic activity than the parent
      ligand, and also might contribute to in vivo effects of SKF-83959. Together,
      these data demonstrate that SKF-83959 is not a highly-biased functionally
      selective D1 ligand, and that its reported behavioral data can be explained
      solely by its partial D1 agonism in canonical signaling pathway(s). Mechanisms
      that have been proposed based on the purported signaling novelty of SKF-83959 at
      PLC should be reconsidered. 

PMID- 24929114
TI  - Structure and functioning mechanism of transketolase.
AB  - Studies of thiamine diphosphate-dependent enzymes appear to have commenced in
      1937, with the isolation of the coenzyme of yeast pyruvate decarboxylase, which
      was demonstrated to be a diphosphoric ester of thiamine. For quite a long time,
      these studies were largely focused on enzymes decarboxylating alpha-keto acids,
      such as pyruvate decarboxylase and pyruvate dehydrogenase complexes.
      Transketolase, discovered independently by Racker and Horecker in 1953 (and named
      by Racker) [1], did not receive much attention until 1992, when crystal X-ray
      structure analysis of the enzyme from Saccharomyces cerevisiae was performed [2].
      These data, together with the results of site-directed mutagenesis, made it
      possible to understand in detail the mechanism of thiamine diphosphate-dependent
      catalysis. Some progress was also made in studies of the functional properties of
      transketolase. The last review on transketolase, which was fairly complete,
      appeared in 1998 [3]. Therefore, the publication of this paper should not seem
      premature. 

PMID- 24929115
TI  - Toward a common aggregation mechanism for a beta-barrel protein family: insights
      derived from a stable dimeric species.
AB  - Delta78Delta is a second generation functional all-beta sheet variant of IFABP
      (intestinal fatty acid binding protein) corresponding to the fragment 29-106 of
      the parent protein. This protein and its predecessor, Delta98Delta (segment 29
      126 of IFABP), were initially uncovered by controlled proteolysis. Remarkably,
      although IFABP and Delta98Delta are monomers in solution, Delta78Delta adopts a
      stable dimeric structure. With the aim of identifying key structural features
      that modulate the aggregation of beta-proteins, we evaluate here the structure
      and aggregation propensity of Delta78Delta. The 2,2,2-trifluoroethanol (TFE)
      induced aggregation of this protein shows a primary nucleation-elongation
      mechanism, characterized by the stabilization of a dimeric nucleus. Its rate of
      production from the co-solvent induced aggregation prone state governs the
      kinetics of polymerization. In this context, the value of Delta78Delta lies in
      the fact that - being a stable dimeric species - it reduces an otherwise
      bimolecular reaction to a unimolecular one. Interestingly, even though
      Delta78Delta and IFABP display similar conformational stability, the abrogated
      form of IFABP shows an enhanced aggregation rate, revealing the ancillary role
      played on this process by the free energy of the native proteins. Delta78Delta
      share with IFABP and Delta98Delta a common putative aggregation-prone central
      peptide. Differences in the exposure/accessibility of this segment dictated by
      the environment around this region might underlie the observed variations in the
      speed of aggregation. Lessons learnt from this natural dimeric protein might shed
      light on the early conformational events leading to beta-conversion from barrels
      to amyloid aggregates. 

PMID- 24929116
TI  - The therapeutic potential of histamine receptor ligands in inflammatory bowel
      disease.
AB  - In the intestine of patients suffering from inflammatory bowel disease
      concentrations of histamine are increased compared to healthy controls. Genetic
      ablation of histamine production in mice ameliorates the course of experimentally
      induced colitis. These observations and first pharmacological studies indicate a
      function of histamine in the pathogenesis of inflammatory bowel disease. However,
      a closer examination reveals that available data are highly heterogeneous,
      limiting the rational design of strategies addressing specific histamine receptor
      subtypes as possible target for pharmacological interaction. However, very
      recently first clinical data indicate that antagonism at the histamine receptor
      subtype H4 provides a beneficial effect in at least the skin. Here, we discuss
      the available data on histamine effects and histamine receptor subtype functions
      in inflammatory bowel disease with a special emphasis on the histamine H4
      receptor. 

PMID- 24929117
TI  - Trolox inhibits osteolytic bone metastasis of breast cancer through both PGE2
      dependent and independent mechanisms.
AB  - Bone is a preferred site of metastasis from breast cancer, and increased
      osteoclast activity is implicated in breast cancer outgrowth in the bone
      microenvironment. Our previous observation of an anti-osteoclastic activity of
      Trolox, a vitamin E analog, led us to investigate whether Trolox inhibits bone
      metastasis and osteolysis caused by breast cancer. Administration of Trolox
      markedly inhibited osteolytic bone metastasis in an experimental metastasis model
      by intracardiac injection of 4T1 breast cancer cells. Trolox inhibited
      proliferation of 4T1 cells in the bone marrow but not in the mammary fat pad. In
      addition, Trolox could reduce tumor burden, osteolysis, and prostaglandin E2
      (PGE2) production induced by direct inoculation of 4T1 cells into the marrow
      cavity of the tibia. Trolox decreased the migratory and invasive activities of
      4T1 cells via PGE2-dependent and independent mechanisms. It also inhibited the
      ability of 4T1 cells to stimulate the expression of receptor activator of nuclear
      factor-kappaB ligand (RANKL), a key cytokine for osteoclast differentiation
      factor, in osteoblasts. In addition, Trolox suppressed RANKL expression in
      osteoblasts induced by soluble factors from 4T1 cells. Furthermore, Trolox
      suppressed 4T1 cell-induced osteoclast differentiation in the co-culture of bone
      marrow cells and osteoblasts via both PGE2-dependent and independent mechanisms.
      Taken together, these results suggest that Trolox inhibits breast cancer cell
      induced osteoclast differentiation and the invasive behavior of cancer cells
      through PGE2-dependent and independent mechanisms, thereby suppressing osteolytic
      bone metastasis of breast cancer. 

PMID- 24929119
TI  - Commercial PCV2a-based vaccines are effective in protecting naturally PCV2b
      infected finisher pigs against experimental challenge with a 2012 mutant PCV2.
AB  - Current commercial PCV2 vaccines are all based on PCV2a and have been shown to be
      effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and
      disease. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of
      mPCV2 with cases of porcine circovirus associated disease (PCVAD) in vaccinated
      herds have raised concerns over emergence of vaccine-escape mutants and reduced
      efficacy of PCV2a-based vaccines. The aim of this study was to determine the
      ability of three commercial PCV2a-based vaccines administered in the presence of
      an ongoing PCV2b infection and passively-acquired anti-PCV2 antibodies to protect
      conventional pigs against experimental challenge with mPCV2 at 11 weeks of age.
      Fifty naturally PCV2b-infected 2-week-old pigs were divided into five treatment
      groups with 10 pigs each. Pigs were unvaccinated (positive and negative controls)
      or vaccinated at 3 (VAC-A, VAC-B, VAC-C) and at 5 weeks of age (VAC-C). At 11
      weeks of age, all pigs except the negative controls were challenged with a 2012
      U.S. strain of mPCV2. The experiment was terminated 21 days after challenge.
      Under the conditions of this study, vaccinated pigs were protected against PCV2
      viremia and lesions whereas non-vaccinated pigs were not. Moreover, concurrent
      PCV2b and mPCV2 infection was demonstrated in all positive controls and 3/10 had
      microscopic lesions consistent with PCVAD while negative controls infected with
      PCV2b alone did not develop PCVAD. The results indicate that concurrent
      PCV2b/mPCV2 infection can trigger PCVAD development and that commercial vaccines
      are effective in protecting conventional pigs against emerging mPCV2 strains. 

PMID- 24929118
TI  - Organization of columnar inputs in the third optic ganglion of a highly visual
      crab.
AB  - Motion information provides essential cues for a wide variety of animal behaviors
      such as mate, prey, or predator detection. In decapod crustaceans and pterygote
      insects, visual codification of object motion is associated with visual
      processing in the third optic neuropile, the lobula. In this neuropile,
      tangential neurons collect motion information from small field columnar neurons
      and relay it to the midbrain where behavioral responses would be finally shaped.
      In highly ordered structures, detailed knowledge of the neuroanatomy can give
      insight into their function. In spite of the relevance of the lobula in
      processing motion information, studies on the neuroarchitecture of this neuropile
      are scant. Here, by applying dextran-conjugated dyes in the second optic
      neuropile (the medulla) of the crab Neohelice, we mass stained the columnar
      neurons that convey visual information into the lobula. We found that the
      arborizations of these afferent columnar neurons lie at four main lobula depths.
      A detailed examination of serial optical sections of the lobula revealed that
      these input strata are composed of different number of substrata and that the
      strata are thicker in the centre of the neuropile. Finally, by staining the
      different lobula layers composed of tangential processes we combined the present
      characterization of lobula input strata with the previous characterization of the
      neuroarchitecture of the crab's lobula based on reduced-silver preparations. We
      found that the third lobula input stratum overlaps with the dendrites of lobula
      giant tangential neurons. This suggests that columnar neurons projecting from the
      medulla can directly provide visual input to the crab's lobula giant neurons. 

PMID- 24929120
TI  - Autophagic activity in the midgut gland of the overwintering harvestmen Gyas
      annulatus (Phalangiidae, Opiliones).
AB  - Juvenile harvestmen Gyas annulatus overwinter in dormancy in hypogean habitats
      for 4-5 months. The ultrastructure of the autophagic structures in their midgut
      epithelium cells was studied by light microscopy, transmission electron
      microscopy (TEM) and immunofluorescence microscopy (IFM) during this non-feeding
      period. Before overwintering (November), autophagic structures were scarce. In
      the middle (January) and at the end of overwintering (March), phagophores,
      autophagosomes and autolysosomes were present in the cytoplasm of both the
      secretory and the digestive midgut epithelium cells, gradually increasing their
      abundance during overwintering. In addition, vacuolization of the cytoplasm
      intensified. Both processes are induced by starvation. Autophagic structures and
      cytoplasm vacuolization enable the reuse of the cell's own components required
      for the maintenance of vital processes during dormancy. While TEM is a much more
      convenient method for recognition of the autophagic structure types and their
      ultrastructure, IFM enables exact counting of these structures.

PMID- 24929121
TI  - Biomarker predictors of cardiac hospitalization in chronic heart failure: a
      recurrent event analysis.
AB  - BACKGROUND: Identification of heart failure (HF) patients at risk for
      hospitalization may improve care and reduce costs. We evaluated 9 biomarkers as
      predictors of cardiac hospitalization in chronic HF. METHODS AND RESULTS: In a
      multicenter cohort of 1,512 chronic HF outpatients, we assessed the association
      between 9 biomarkers and cardiac hospitalization with the use of a recurrent
      events approach. Over a median follow-up of 4 years, 843 participants experienced
      >= 1 hospitalizations (total 2,178 hospitalizations). B-type natriuretic peptide
      (BNP) and troponin I (TnI) exhibited the strongest associations with risk of
      hospitalization (hazard ratio [HR] 3.8 [95% confidence interval (CI) 2.9-4.9] and
      HR 3.3 [95% CI 2.8-3.9]; 3rd vs 1st tertiles). Soluble Fms-like tyrosine kinase
      receptor 1 (sFlt-1) exhibited the next strongest association (HR 2.8 [95% CI 2.4
      3.4]), followed by soluble Toll-like receptor 2 (HR 2.3 [95% CI 2.0-2.8]) and
      creatinine (HR 1.9 [95% CI 1.6-2.4]). Within ischemic/nonischemic subgroups, BNP
      and TnI remained most strongly associated. Except for creatinine, HRs for all
      biomarkers studied were smaller within the ischemic subgroup, suggesting greater
      importance of cardiorenal interactions in decompensation of ischemic HF.
      CONCLUSION: Although BNP and TnI exhibited the strongest associations with
      hospitalization, etiology-dependent associations for the remaining biomarkers
      suggest etiology-specific mechanisms for HF exacerbation. sFlt-1 exhibited a
      strong association with cardiac hospitalization, highlighting its potential role
      as a biomarker of HF morbidity.

PMID- 24929122
TI  - Phylogenetic characterization of VP6 gene (inner capsid) of porcine rotavirus C
      collected in Japan.
AB  - Porcine rotavirus C (RVC) has been often detected in sporadic cases or outbreaks
      of diarrhea in suckling and weaned pigs. Previous surveillance studies using both
      enzyme-linked immunosorbent assays and reverse-transcription polymerase chain
      reaction in some countries including Japan and the United States have
      demonstrated a high prevalence of porcine RVCs. In order to understand the
      phylogenetic relatedness of RVCs, we performed genetic analysis of VP6 gene
      encoding inner capsid protein by using 22 porcine RVC strains collected in Japan
      from 2002 to 2010. Comparative analyses of the VP6 nucleotide and amino acid
      sequences from these porcine RVCs exhibited lower sequence identities than those
      from human and bovine RVCs. The phylogenetic analysis of VP6 gene of RVC
      indicated the presence of seven clusters (tentatively assigned I1-I7) according
      to host species with cut-off values of 87% at the nucleotide level, and VP6 genes
      of porcine RVCs were divided into five genotypes. These findings indicate that
      multiple porcine RVC strains with distinctive genotypes are broadly spreading and
      circulating among farms in Japan. Our data may provide important insights in
      understanding evolutionary dynamics of RVCs. 

PMID- 24929124
TI  - Screening and identification of soybean seed-specific genes by using integrated
      bioinformatics of digital differential display, microarray, and RNA-seq data.
AB  - Soybean is one of the most economically important crops in the world. Soybean
      seeds have abundant protein and lipid content and very high economic value. In
      this study, a total of 184 seed-specific genes were obtained using online
      microarray databases, DDD, and RNA-seq data. The reported seed-specific genes in
      soybean and the 184 seed-specific genes analyzed in this paper were compared. Of
      the screened genes, 26 were common to both previous reports and the current
      screening. Meanwhile, 90 of the 184 genes have homologous counterparts in
      Arabidopsis, among which 24 have seed-specific expression, as indicated by
      microarray data for Arabidopsis. Furthermore, promoter analysis showed that
      almost all seed-specific genes contain at least one seed specific-related
      element. Seed-specific element Skn-1 motif exists in most, if not all, of the
      seed-specific genes screened. Five genes were randomly selected from 184 soybean
      seed specific gene pool and their expressions were quantified using quantitative
      real time polymerase chain reaction (qRT-PCR) to further confirm the specificity
      of the screened genes. The results indicated that all five genes showed seed
      specific expression. Moreover, the identification of genes with seed-specific
      expression screened in this study provides information valuable to the in-depth
      study of soybean. 

PMID- 24929125
TI  - Frequency of MEFV gene mutations in Hatay province, Mediterranean region of
      Turkey and report of a novel missense mutation (I247V).
AB  - In the present study, 1000 patients with clinical suspicion of FMF were
      retrospectively reviewed to determine the spectrum of MEFV gene mutations by
      using DNA sequence analysis between September, 2008 and April, 2012. Sixteen
      different mutations and 55 different genotypes were detected in 618 of 1000
      patients. Among 16 different mutations, R202Q (21.35%) was the most frequently
      observed mutation; followed by E148Q (8.85%), M694V (7.95%), M680I (2.40%), V726A
      (1.85%), M694I (0.95%), A744S (0.80%), R761H (0.55%), P283L (0.35%), K695R
      (0.20%), E230K (0.15%), L110P (0.10%), I247V (0.05%), G196W (0.05%) and G304R
      (0.05%). In the present study, a novel missense mutation (I247V) and a silent
      variant (G150G) were identified in the MEFV gene. On the other hand, P238L, G632A
      and G304R mutations are the first cases reported from Turkey. Our results
      indicated that MEFV mutations are highly heterogeneous in our study population as
      in other regions of Turkey and mutation screening techniques such as PCR-RFLP,
      amplification refractory mutation system or reverse hybridization do not
      adequately detect uncommon or novel mutations. Therefore, it was proven that
      sequence analysis of the MEFV gene could be useful for detection of rare or
      unknown mutations. 

PMID- 24929123
TI  - Differential roles of an Anopheline midgut GPI-anchored protein in mediating
      Plasmodium falciparum and Plasmodium vivax ookinete invasion.
AB  - Novel strategies to directly thwart malaria transmission are needed to maintain
      the gains achieved by current control measures. Transmission-blocking
      interventions (TBIs), namely vaccines and drugs targeting parasite or mosquito
      molecules required for vector-stage parasite development, have been recognized as
      promising approaches for preventing malaria transmission. However, the number of
      TBI targets is limited and their degree of conservation among the major vector
      parasite systems causing human disease is unclear. Therefore, discovery and
      characterization of novel proteins involved in vector-stage parasite development
      of Plasmodium falciparum and Plasmodium vivax is paramount. We mined the recent
      Anopheles gambiae midgut lipid raft proteome for putative mosquito-derived TBI
      targets and characterized a secreted glycoconjugate of unknown function, AgSGU.
      We analyzed molecular variation in this protein among a range of anopheline
      mosquitoes, determined its transcriptomic and proteomic profiles, and conducted
      both standard and direct membrane feeding assays with P. falciparum (lab/field)
      and P. vivax (field) in An. gambiae and Anopheles dirus. We observed that alpha
      AgSGU antibodies significantly reduced midgut infection intensity for both lab
      and field isolates of P. falciparum in An. gambiae and An. dirus. However, no
      transmission-reducing effects were noted when comparable concentrations of
      antibodies were included in P. vivax-infected blood meals. Although antibodies
      against AgSGU exhibit transmission-reducing activity, the high antibody titer
      required for achieving 80% reduction in oocyst intensity precludes its
      consideration as a malaria mosquito-based TBI candidate. However, our results
      suggest that P. falciparum and P. vivax ookinetes use a different repertoire of
      midgut surface glycoproteins for invasion and that alpha-AgSGU antibodies, as
      well as antibodies to other mosquito-midgut microvillar surface proteins, may
      prove useful as tools for interrogating Plasmodium-mosquito interactions. 

PMID- 24929126
TI  - Isolation and characterization of three TaYUC10genes from wheat.
AB  - YUCCA protein participates in a key rate-limiting step in the tryptophan
      dependent pathway for auxin biosynthesis and is involved in numerous processes
      during plant development. In this study, the genomic and cDNA sequences of three
      TaYUC10 homoeologous genes were isolated. These sequences showed a very high
      conservation in coding region and the exon/intron structure, whereas their intron
      lengths were different. The cDNA and polypeptide chains of the three TaYUC10
      genes were highly similar. These genes were most homologous to BdYUC10. Location
      analysis showed that TaYUC10.1 was present in chromosome 5BL. TaYUC10.3 was
      expressed in all parts of the wheat, but was predominant in the reproductive
      organs of mature wheat, such as flowering spikelets or fertilized embryos. In the
      fertilized embryos 28d post-anthesis, expression of TaYUC10.3 was clearly
      increased with the development of seeds. This indicates that TaYUC genes may play
      a vital role in seed development. TaYUC10.3 overexpressed in Arabidopsis had a
      typical phenotype, excessive auxin accumulation also seen in higher plants, and
      showed increased spacing of silique and downward curling of the blade margin.
      Sterility was observed in adult transgenic plants, becoming more severe in late
      development. The floral structures of sterile plants were not integrated. TaYUC10
      may be required for numerous wheat growth processes, including flower and seed
      development. 

PMID- 24929127
TI  - Global expression profile of telomerase-associated genes in HeLa cells.
AB  - Telomerase is a specialized nucleoprotein enzyme complex that maintains the
      telomere length. The telomerase reverse transcriptase (TERT) is the catalytically
      active component of the telomerase complex. In humans, the protein component
      (hTERT) and RNA component (hTR) are found to differentially express in cancer
      cells. In contrast to differentiated cells, most of the cancer cells overexpress
      hTERT, which is needed to maintain the proliferative potential of cells. The
      overexpression of telomerase is not proportionate to telomere length in cancer
      cells, suggesting that the immortalizing phenotype can be mediated through other
      factors in addition to telomere length. To investigate the role of hTERT in
      immortalizing process, loss of gene function studies were carried out. Short
      interfering RNA (siRNA) and short hairpin RNA (shRNA) against hTERT showed the
      reduction of hTERT transcript, reduction of telomerase activity and alteration of
      gene expression in HeLa cells. The molecular basis of proliferative capacity of
      hTERT was investigated by gene expression microarray. Analysis of microarray data
      for HeLa cells following siRNA and shRNA mediated knockdown of hTERT showed that
      80 genes were upregulated and 73 genes downregulated. Out of these, 37 genes are
      known to be involved in cancer. Further analyses of previously known genes
      involved in cancer like KLF4, FGF2, IRF-9 and PLAU by Real Time PCR showed their
      upregulation. We are documenting for the first time the effect of knocking down
      hTERT on expression of KLF4 and FGF2. Interestingly, it has been earlier reported
      that KLF4 and FGF2 up-regulate the expression of hTERT in cancer cells. This
      suggests that hTERT may be subject to its own auto-regulatory effects. 

PMID- 24929128
TI  - Construction of a standard reference plasmid containing seven target genes for
      the detection of transgenic cotton.
AB  - Insect resistance and herbicide tolerance are the dominant traits of
      commercialized transgenic cotton. In this study, we constructed a general
      standard reference plasmid for transgenic cotton detection. Target genes,
      including the cowpea trypsin gene cptI, the insect resistance gene cry1Ab/1Ac,
      the herbicide tolerance gene cp4-epsps, the Agrobacterium tumefaciens nopaline
      synthase (Nos) terminator that exists in transgenic cotton and part of the
      endogenous cotton SadI gene were amplified from plasmids pCPT1, pBT, pCP4 and
      pBI121 and from DNA of the nontransgenic cotton line K312, respectively. The
      genes cry1Ab/1Ac and cptI, as well as cp4-epsps and the Nos terminator gene, were
      ligated together to form the fusion genes cptI-Bt and cp4-Nos, respectively, by
      overlapping PCR. We checked the validity of genes Sad1, cptI-Bt and cp4-Nos by
      DNA sequencing. Then, positive clones of cptI-Bt, cp4-Nos and Sad1 were digested
      with the corresponding restriction enzymes and ligated sequentially into vector
      pCamBIA2300, which contains the CAMV 35S promoter and nptII gene, to form the
      reference plasmid pMCS. Qualitative detection showed that pMCS is a good positive
      control for transgenic cotton detection. Real-time PCR detection efficiencies
      with pMCS as a calibrator ranged from 94.35% to 98.67% for the standard curves of
      the target genes (R(2)?0.998). The relative standard deviation of the mean value
      for the known sample was 11.95%. These results indicate that the strategy of
      using the pMCS plasmid as a reference material is feasible and reliable for the
      detection of transgenic cotton. Therefore, this plasmid can serve as a useful
      reference tool for qualitative and quantitative detection of single or stacked
      trait transgenic cotton, thus paving the way for the identification of various
      products containing components of transgenic cotton. 

PMID- 24929129
TI  - Preparation, quality criteria, and properties of human blood platelet lysate
      supplements for ex vivo stem cell expansion.
AB  - Most clinical applications of human multipotent mesenchymal stromal cells (MSCs)
      for cell therapy, tissue engineering, regenerative medicine, and treatment of
      immune and inflammatory diseases require a phase of isolation and ex vivo
      expansion allowing a clinically meaningful cell number to be reached. Conditions
      used for cell isolation and expansion should meet strict quality and safety
      requirements. This is particularly true for the growth medium used for MSC
      isolation and expansion. Basal growth media used for MSC expansion are
      supplemented with multiple nutrients and growth factors. Fetal bovine serum (FBS)
      has long been the gold standard medium supplement for laboratory-scale MSC
      culture. However, FBS has a poorly characterized composition and poses risk
      factors, as it may be a source of xenogenic antigens and zoonotic infections. FBS
      has therefore become undesirable as a growth medium supplement for isolating and
      expanding MSCs for human therapy protocols. In recent years, human blood
      materials, and most particularly lysates and releasates of platelet concentrates
      have emerged as efficient medium supplements for isolating and expanding MSCs
      from various origins. This review analyzes the advantages and limits of using
      human platelet materials as medium supplements for MSC isolation and expansion.
      We present the modes of production of allogeneic and autologous platelet
      concentrates, measures taken to ensure optimal pathogen safety profiles, and
      methods of preparing PLs for MSC expansion. We also discuss the supply of such
      blood preparations. Produced under optimal conditions of standardization and
      safety, human platelet materials can become the future 'gold standard' supplement
      for ex vivo production of MSCs for translational medicine and cell therapy
      applications. 

PMID- 24929130
TI  - Systems biology of synaptic plasticity: a review on N-methyl-D-aspartate receptor
      mediated biochemical pathways and related mathematical models.
AB  - Synaptic plasticity, an emergent property of synaptic networks, has shown strong
      correlation to one of the essential functions of the brain, memory formation.
      Through understanding synaptic plasticity, we hope to discover the modulators and
      mechanisms that trigger memory formation. In this paper, we first review the well
      understood modulators and mechanisms underlying N-methyl-D-aspartate receptor
      dependent synaptic plasticity, a major form of synaptic plasticity in
      hippocampus, and then comment on the key mathematical modelling approaches
      available in the literature to understand synaptic plasticity as the integration
      of the established functionalities of synaptic components.

PMID- 24929131
TI  - Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor
      2 reduces adult parasite numbers and affects the fertility of female worms
      following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus)
      with B. malayi infective larvae.
AB  - Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2
      in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in
      reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi
      L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing
      of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm
      CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative
      protective mechanism. These observations suggest that Bm-CPI-2M is a promising
      prophylactic and anti-fecundity vaccine candidate.

PMID- 24929132
TI  - Small molecule analogues of the immunomodulatory parasitic helminth product ES-62
      have anti-allergy properties.
AB  - ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae,
      exhibits anti-inflammatory properties by virtue of covalently attached
      phosphorylcholine moieties. Screening of a library of ES-62 phosphorylcholine
      based small molecule analogues (SMAs) revealed that two compounds, termed 11a and
      12b, mirrored the helminth product both in inhibiting mast cell degranulation and
      cytokine responses in vitro and in preventing ovalbumin-induced Th2-associated
      airway inflammation and eosinophil infiltration of the lungs in mice.
      Furthermore, the two SMAs inhibited neutrophil infiltration of the lungs when
      administered therapeutically. ES-62-SMAs 11a and 12b thus represent starting
      points for novel drug development for allergies such as asthma. 

PMID- 24929133
TI  - A multi-component integrated approach for the elimination of schistosomiasis in
      the People's Republic of China: design and baseline results of a 4-year cluster
      randomised intervention trial.
AB  - Despite major successes in its control over the past 50years, schistosomiasis
      japonica continues to be a public health problem in the People's Republic of
      China (P.R. China). Historically, the major endemic foci occur in the lakes and
      marshlands along the Yangtze River, areas where transmission interruption has
      proven difficult. The current endemic situation may alter due to the closure of
      the Three Gorges Dam. Considerable environmental and ecological changes are
      anticipated that may result in new habitats for the oncomelanid intermediate
      snail host of Schistosoma japonicum (Sj), thereby increasing the risk of
      transmission. The current national control program for P.R. China involves a
      multi-component integrated strategy but, despite targeting multiple transmission
      pathways, certain challenges remain. As the Chinese government pushes towards
      elimination, there is a requirement for additional tools, such as vaccination,
      for long-term prevention. Whereas the zoonotic nature of schistosomiasis japonica
      adds to the complexity of control, it provides a unique opportunity to develop a
      transmission blocking vaccine targeting bovines to assist in the prevention of
      human infection and disease. Mathematical modelling has shown that control
      options targeting the various transmission pathways of schistosomiasis japonica
      and incorporating bovine vaccination, mass human chemotherapy and mollusciciding
      could lead to its elimination from P.R. China. Here we present the study design
      and baseline results of a four-year cluster randomised intervention trial we are
      undertaking around the schistosomiasis-endemic Dongting Lake in Hunan Province
      aimed at determining the impact on schistosome transmission of the multi
      component integrated control strategy, including bovine vaccination using a
      heterologous "prime-boost" delivery platform based on the previously tested
      SjCTPI vaccine. 

PMID- 24929134
TI  - Destabilization domain approach adapted for regulated protein expression in the
      protozoan parasite Entamoeba histolytica.
AB  - A plethora of information has been gained by sequencing the genome of the human
      parasite Entamoeba histolytica, however a lack of robust genetic tools hampers
      experimental elucidation of gene functions. We adapted the destabilization domain
      approach for modulation of protein levels in E. histolytica using the
      destabilization domains of FK506 binding protein (ddFKBP) and dihydrofolate
      reductase (ddDHFR), respectively. In our studies, the ddFKBP appears to be more
      tightly regulated than ddDHFR, with minimal detectable protein in trophozoites in
      the absence of the stabilizing compound. The on- and off-rate kinetics for ddFKBP
      were rapid, with stabilization and degradation within 3h of addition or removal
      of stabilizing compound, respectively. The kinetics for ddDHFR was different,
      with rapid stabilization (within 3h of stabilizing compound being added) but much
      slower degradation (protein not destabilized until 24h after compound removal).
      Furthermore, we demonstrated that for the ddFKBP, the standard stabilizing
      compound Shield-1 could be effectively replaced by two cheaper alternatives
      (rapamycin and FK506), indicating that the more cost-effective alternatives are
      viable options for use with E. histolytica. Thus, the destabilization domain
      approach represents a powerful method to study protein functions in E.
      histolytica and adds to the catalog of genetic tools that could be used to study
      this important human pathogen. 

PMID- 24929135
TI  - Fish pathogens near the Arctic Circle: molecular, morphological and ecological
      evidence for unexpected diversity of Diplostomum (Digenea: Diplostomidae) in
      Iceland.
AB  - Host-parasite systems at high latitudes are promising model systems for detecting
      and predicting the impact of accelerated environmental change. A major challenge
      is the lack of baselines for the diversity and distribution of parasites in
      Arctic wildlife, especially in the freshwater environment. Here we present the
      first known estimates of the species diversity and host associations of
      Diplostomum spp. in sub-Arctic freshwater ecosystems of the Palaearctic. Our
      analyses integrating different analytical approaches, phylogenies based on
      mitochondrial and nuclear DNA, estimates of genetic divergence, character-based
      barcoding, morphological examination, precise detection of microhabitat
      specialisation and host use, led to the discovery of one described and five
      putative new species that complete their life-cycles within a fairly narrow
      geographic area in Iceland. This increases the species richness of Diplostomum in
      Iceland by 200% and raises the number of molecularly characterised species from
      the Palaearctic to 17 species. Our results suggest that the diversity of
      Diplostomum spp. is underestimated globally in the high latitude ecosystems and
      call for a cautionary approach to pathogen identification in developing the much
      needed baselines of pathogen diversity that may help detect effects of climate
      change in the freshwater environment of the sub-Arctic. 

PMID- 24929136
TI  - Manipulation of host-resource dynamics impacts transmission of trophic parasites.
AB  - Many complex life cycle parasites rely on predator-prey interactions for
      transmission, whereby definitive hosts become infected via the consumption of an
      infected intermediate host. As such, these trophic parasites are embedded in the
      larger community food web. We postulated that exposure to infection and, hence,
      parasite transmission are inherently linked to host foraging ecology, and that
      perturbation of the host-resource dynamic will impact parasite transmission
      dynamics. We employed a field manipulation experiment in which natural
      populations of the eastern chipmunk (Tamias striatus) were provisioned with a
      readily available food resource in clumped or uniform spatial distributions.
      Using replicated longitudinal capture-mark-recapture techniques, replicated
      supplemented and unsupplemented control sites were monitored before and after
      treatment for changes in infection levels with three gastro-intestinal helminth
      parasites. We predicted that definitive hosts subject to food supplementation
      would experience lower rates of exposure to infective intermediate hosts,
      presumably because they shifted their diet away from the intermediate host
      towards the more readily available resource (sunflower seeds). As predicted,
      prevalence of infection by the trophically transmitted parasite decreased in
      response to supplemental food treatment, but no such change in infection
      prevalence was detected for the two directly transmitted parasites in the system.
      The fact that food supplementation only had an impact on the transmission of the
      trophically transmitted parasite, and not the directly transmitted parasites,
      supports our hypothesis that host foraging ecology directly affects exposure to
      parasites that rely on the ingestion of intermediate hosts for transmission. We
      concluded that the relative availability of different food resources has
      important consequences for the transmission of parasites and, more specifically,
      parasites that are embedded in the food web. The broader implications of these
      findings for food web dynamics and disease ecology are discussed. 

PMID- 24929137
TI  - Identification of three doublesex genes in the monogonont rotifer Brachionus
      koreanus and their transcriptional responses to environmental stressor-triggered
      population growth retardation.
AB  - Doublesex and Mab-3-related transcription factor (Dmrt) gene family members have
      rarely been identified or characterized in aquatic invertebrates. In this study,
      we identified and characterized three DMdomain-containing genes - Dmrt11E,
      Dmrt93B, and Dmrt99B - in the monogonont rotifer, Brachionus koreanus. DMdomains
      of the proteins encoded by the B.koreanus Dmrt (Bk-Dmrt) genes had high
      similarities to DM domains of other invertebrate species. To understand the
      potential effects of environmental stressors on the transcriptional expression of
      Dmrt genes in rotifers, we exposed B.koreanus to a wide range of UV-B radiation
      and different concentrations of benzo[a]pyrene (B[a]P) over different time
      courses. Transcript levels of all Bk-Dmrt genes decreased significantly in
      response to relatively high doses of UV-B irradiation, and were also
      downregulated in response to exposure to UV-B radiation over time. Transcript
      levels of all Bk-Dmrt genes were downregulated in response to B[a]P exposure for
      24h. This decrease in expression of all Bk-Dmrt genes was concomitant with the
      growth retardation induced by UV-B and B[a]P exposure. We concluded that both
      environmental stressors have detrimental effects on transcriptional regulation of
      all Bk-Dmrt genes, especially relatively high doses of these stressors, leading
      to growth retardation. However, further studies are required to better understand
      the potential role of Dmrt genes in environmental stressor-triggered growth
      retardation in the rotifer B.koreanus. 

PMID- 24929138
TI  - Cylindrospermopsin decreases the oxidative burst capacity of human neutrophils.
AB  - Cylindrospermopsin (CYN), a cyanobacterial toxin, presents a risk to human health
      due to its relatively high chemical stability, a global spread of its producers
      and its occurrence in drinking-water reservoirs. Despite a broad interest in its
      toxicity to eukaryotes, little is known about the potential effects of CYN on the
      human immune system. Here, we have investigated whether CYN (0.01-1.0 MUg mL(-1))
      can affect the function of human peripheral blood neutrophils during a 1-h
      exposure. Using whole-blood assays, we have studied an oxidative burst,
      phagocytic activity, cell number and viability. At all studied concentrations,
      CYN had the ability to significantly decrease the level of reactive oxygen
      species (ROS) production in stimulated neutrophils. The greatest ROS decline was
      observed for the highest assayed concentration, maximally exceeding 65% (a mean
      decrease of 22.8%). A depressed level of ROS was also found in unstimulated cells
      at all studied concentrations of the toxin. At the same time, CYN did not
      significantly affect the percentage of phagocytic cells or the number of engulfed
      bacteria. Neither was any induction of apoptosis or significant necrosis found.
      From the results we postulate that CYN at environmentally-relevant concentrations
      can reduce the ability of human neutrophils to fight infections through a
      decrease in NADPH oxidase-mediated production of ROS. 

PMID- 24929139
TI  - Venom toxicity and composition in three Pseudomyrmex ant species having different
      nesting modes.
AB  - We aimed to determine whether the nesting habits of ants have influenced their
      venom toxicity and composition. We focused on the genus Pseudomyrmex
      (Pseudomyrmecinae) comprising terrestrial and arboreal species, and, among the
      latter, plant-ants that are obligate inhabitants of myrmecophytes (i.e., plants
      sheltering ants in hollow structures). Contrary to our hypothesis, the venom of
      the ground-dwelling species, Pseudomyrmex termitarius, was as efficacious in
      paralyzing prey as the venoms of the arboreal and the plant-ant species,
      Pseudomyrmex penetrator and Pseudomyrmex gracilis. The lethal potency of P.
      termitarius venom was equipotent with that of P. gracilis whereas the venom of P.
      penetrator was less potent. The MALDI-TOF MS analysis of each HPLC fraction of
      the venoms showed that P. termitarius venom is composed of 87 linear peptides,
      while both P. gracilis and P. penetrator venoms (23 and 26 peptides,
      respectively) possess peptides with disulfide bonds. Furthermore, P. penetrator
      venom contains three hetero- and homodimeric peptides consisting of two short
      peptidic chains linked together by two interchain disulfide bonds. The large
      number of peptides in P. termitarius venom is likely related to the large
      diversity of potential prey plus the antibacterial peptides required for nesting
      in the ground. Whereas predation involves only the prey and predator, P.
      penetrator venom has evolved in an environment where trees, defoliating insects,
      browsing mammals and ants live in equilibrium, likely explaining the diversity of
      the peptide structures. 

PMID- 24929140
TI  - Risk of chronic and end stage kidney disease in patients with nephrolithiasis.
AB  - PURPOSE: We examine kidney stone disease as a potential risk factor for chronic
      kidney disease, end stage kidney disease and treatment with dialysis. MATERIALS
      AND METHODS: The NHANES (National Health and Nutrition Examination Survey) 2007
      2010 database was interrogated for patients with a history of kidney stones.
      Demographics and comorbid conditions including age, gender, body mass index,
      diabetes, hemoglobin A1c, hypertension, gout and smoking were also assessed.
      Multivariate analysis adjusting for patient demographics and comorbidities was
      performed to assess differences in the prevalence of chronic kidney disease and
      treatment with dialysis between the 2 groups. History of nephrolithiasis was
      assessed with the question, "Have you ever had kidney stones?" Chronic kidney
      disease was defined as an estimated glomerular filtration rate of less than 60
      ml/minute/1.73 m(2) and/or a urinary albumin-to-creatinine ratio greater than 30
      mg/gm. Statistical calculations were performed using Stata(r) software with
      determinations of p values and 95% CI where appropriate. RESULTS: The study
      included an analysis of 5,971 NHANES participants for whom data on chronic kidney
      disease and kidney stones were available, of whom 521 reported a history of
      kidney stones. On multivariate analysis a history of kidney stones was associated
      with chronic kidney disease and treatment with dialysis (OR 1.50, 1.10-2.04, p =
      0.013 and OR 2.37, 1.13-4.96, p = 0.025, respectively). This difference appeared
      to be driven by women, where a history of kidney stones was associated with a
      higher prevalence of chronic kidney disease (OR 1.76, 1.13-2.763, p = 0.016) and
      treatment with dialysis (OR 3.26, 1.48-7.16, p = 0.004). There was not a
      significant association between kidney stone history and chronic kidney disease
      or treatment with dialysis in men. CONCLUSIONS: Kidney stone history is
      associated with an increased risk of chronic kidney disease and treatment with
      dialysis among women even after adjusting for comorbid conditions. Large scale
      prospective studies are needed to further characterize the relationship between
      nephrolithiasis and chronic kidney disease.

PMID- 24929141
TI  - Calcium signalling as a hub for translational medicine a starting point to model
      life.

PMID- 24929142
TI  - Genetic polymorphisms in the Toll-like receptor signalling pathway in
      Helicobacter pylori infection and related gastric cancer.
AB  - BACKGROUND: Gastric cancer (GC) is a progressive process initiated by
      Helicobacter pylori-induced inflammation. Initial recognition of H. pylori
      involves Toll-like receptors (TLRs), central molecules in the host inflammatory
      response. Here, we investigated the association between novel polymorphisms in
      genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2,
      CD14 and TIRAP, and risk of H. pylori infection and related GC. METHODS: A case
      control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases
      and 223 controls with functional dyspepsia) was conducted. Twenty-five
      polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR-RFLP and
      real-time PCR. RESULTS: Seven polymorphisms showed significant associations with
      GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4
      rs10759932, TLR4 rs2149356 and CD14 -260 C/T). In multivariate analyses, TLR4
      rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20-10.65). TLR4
      rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41
      0.86). Statistical analyses assessing the joint effect of H. pylori infection and
      the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD
      2, LBP and TIRAP polymorphisms). CONCLUSIONS: Novel polymorphisms in TLR2, TLR4,
      MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR
      signalling pathway, showed clear associations with H. pylori-related GC in
      Chinese.

PMID- 24929143
TI  - Killer-cell immunoglobulin-like receptors and falciparum malaria in southwest
      Nigeria.
AB  - Killer-cell immunoglobulin-like receptors (KIRs) are a group of natural killer
      cell receptors (NKRs) that regulate NK-cell-mediated production of interferon
      gamma (IFN-gamma) in response to infection. These receptors have recently been
      suggested to influence the severity of clinical Plasmodium falciparum malaria
      infection. We examined the KIR locus in relation to malaria in children from
      southwest Nigeria. Sequence specific priming (SSP)-PCR was used to detect the KIR
      genes. The presence or absence of fifteen different KIR genes was determined in
      each individual and the proportions compared across 3 clinical groups;
      asymptomatic malaria, uncomplicated clinical malaria and severe clinical malaria.
      The genes KIR2DL5, KIR2DS3 and KIR2DS5 were present in a significantly higher
      proportion of individuals in the asymptomatic control group than in the malaria
      cases. Furthermore, KIR2DS3 and KIR2DS5 were present in a higher proportion of
      uncomplicated malaria cases than severe malaria cases. Carriage c-AB2 genotype
      (which comprises all centromeric KIR genes including KIR2DL5, KIR2DS3 and
      KIR2DS5) decreases with severity of the disease suggesting that the KIR AB
      profile might be associated with protection from severe malaria infection in this
      population in Nigeria. 

PMID- 24929144
TI  - KIR3DL1-HLA-Bw4 combination and IL28B polymorphism predict response to Peg-IFN
      and ribavirin with and without telaprevir in chronic hepatitis C.
AB  - Natural killer cells play a key role in the immune control of viral infections.
      Killer immunoglobulin-like receptors (KIRs) regulate natural killer cell
      activation and inhibition through the recognition of their cognate HLA class I
      ligands. We assessed the predictive factors of a sustained virological response
      (SVR) in 200 Japanese patients with chronic genotype 1b hepatitis C who were
      treated with telaprevir (TVR), pegylated-interferon-alpha2b (PEG-IFN), and
      ribavirin (RBV) triple therapy (92 patients) or PEG-IFN/RBV therapy alone (108
      patients). Sixteen KIR genotypes, HLA-A, -B and -C ligands, and an interleukin
      (IL) 28B polymorphism (rs8099917) were analyzed. We observed that triple therapy,
      white blood cell count, hemoglobin value, hepatitis C viral load, a rapid
      virological response (RVR), IL28B TT genotype, and KIR3DL1-HLA-Bw4 genotype were
      associated with an SVR. In multivariate regression analysis, we identified an RVR
      (P < 0.000001; odds ratio [OR] = 20.95), the IL28B TT genotype (P = 0.00014; OR =
      5.53), and KIR3DL1-HLA-Bw4 (P = 0.004, OR = 3.42) as significant independent
      predictive factors of an SVR. In conclusion, IL28B and KIR3DL1/HLA-Bw4 are
      independent predictors of an SVR in Japanese patients infected with genotype 1b
      HCV receiving TVR/PEG-IFN/RBV or PEG-IFN/RBV therapy.

PMID- 24929145
TI  - HLA-G gene expression influenced at allelic level in association with end stage
      renal disease and acute allograft rejection.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major
      histocompatibility complex class-I molecule associated with immunosuppressive
      function. We have evaluated the impact of HLA-G allele associated with
      untranslated-region (UTR)-haplotype in end stage renal disease (ESRD) and acute
      allograft rejection (AR) cases. The mRNA levels of different HLA-G isoforms were
      evaluated in ESRD and AR cases. Subsequently, the total HLA-G mRNA levels and
      protein concentration were evaluated against its UTR-haplotype among ESRD and AR
      cases. METHODOLOGY: Sequence based typing of the promoter region was carried-out
      to evaluate the impact of HLA-G haplotype in 350 ESRD cases and 300 controls. HLA
      G gene expression was evaluated at the transcriptional level using semi
      quantitative and quantitative PCR, whereas protein concentration was determined
      by ELISA among both cases and control. RESULTS: Increased risk was observed for
      G*01:01:01:03, G*01:01:02, G*01:06 and G*01:05:N haplotypes while G*01:01:01:01
      and G*01:04:01 haplotypes showed a protective effect in ESRD and AR cases. Higher
      level of soluble HLA-G isoforms (G5 and G6) was observed among ESRD cases.
      Reduced levels of soluble isoform (G5) and increased levels of membrane bound (G1
      and G3) isoforms were found among AR cases, revealing risk association. Decreased
      HLA-G expression was observed at both mRNA and protein level for G*01:01:01:03
      and G*01:05:N haplotypes in ESRD and AR cases. CONCLUSIONS: These results suggest
      that the variation in the expression profile of membrane bound and soluble
      isoforms may modulate the risk for ESRD and AR. UTR-haplotypes appear to be
      involved in different HLA-G expression patterns at transcriptional and
      translational levels.

PMID- 24929146
TI  - Potentiated anti-microsporidial activity of Lactobacillus acidophilus CH1
      bacteriocin using gold nanoparticles.
AB  - Through increased awareness and improved diagnostics, microsporidiosis has now
      been identified in a broader range of human populations; however current
      therapies are inconsistently effective. Recently, probiotics were determined as
      means for the control of intestinal parasitic infections through their secretory
      products; bacteriocins. This is the first study on the effect of bacteriocin
      produced by Lactobacillus acidophilus CH1 bacteriocin, with or without gold
      nanoparticles (Au-NPs), against intestinal microsporidiosis in immunosuppressed
      mice. Fecal and intestinal spore loads, besides viability, extrusion and
      infectivity of spores from treated animals were assessed. Results showed that the
      anti-microsporidial effects of bacteriocin were significantly potent. This
      efficiency was further potentiated upon conjugating bacteriocins with Au-NPs, as
      it induced a strikingly sustained reduction in fecal spore shedding after
      cessation of therapy by 1 week (94.26%). Furthermore, reduction in intestinal
      spore load was highest in bacteriocin/Au-NPs-inoculated mice (89.7%) followed by
      bacteriocin-inoculated group (73.5%). Spores encountered from stool of
      bacteriocin/Au-NPs group showed 92.4% viability, versus 93.7% in bacteriocin
      group. Spore extrusion and infectivity were most inhibited by exposure to
      bacteriocin/Au-NPs. Safety of bacteriocin/Au-NPs was also verified. Thus,
      considering the results of the present work, L. acidophilus CH1-derived
      bacteriocin can present a powerful safe therapy against intestinal
      microsporidiosis.

PMID- 24929147
TI  - Muller cell activation and photoreceptor depletion in a mice model of congenital
      ocular toxoplasmosis.
AB  - Muller glial cells are critically involved in retinal inflammatory processes.
      Here, we investigate the activation of Muller cells in a model of congenital
      ocular toxoplasmosis (OT). Four weeks after infection, retinal sections were
      studied immunohistochemically using the markers glial fibrillary acidic protein
      (GFAP) and vimentin. Muller cells showed strong up-regulation of both markers, as
      well as a deteriorated morphology in all infected retinas. Moreover, cell density
      and color intensity of the outer nuclear layer (ONL) of photoreceptors were
      decreased. Our results indicate that the severe retinal damage and loss of vision
      observed in human OT may be not only directly caused by infection but rather
      mediated by infection induced reactive gliosis. 

PMID- 24929148
TI  - Development of a combined in vitro cell culture--quantitative PCR assay for
      evaluating the disinfection performance of pulsed light for treating the
      waterborne enteroparasite Giardia lamblia.
AB  - Giardia lamblia is a flagellated protozoan parasite that is recognised as a
      frequent cause of water-borne disease in humans and animals. We report for the
      first time on the use of a combined in vitro HCT-8 cell culture-quantitative PCR
      assay for evaluating the efficacy of using pulsed UV light for treating G.
      lamblia parasites. Findings showed that current methods that are limited to using
      vital stains before and after cyst excystation are not appropriate for monitoring
      or evaluating cyst destruction post PUV-treatments. Use of the human ileocecal
      HCT-8 cell line was superior to that of the human colon Caco-2 cell line for in
      vitro culture and determining PUV sensitivity of treated cysts. G. lamblia cysts
      were also shown to be more resistant to PUV irradiation compared to treating
      similar numbers of Cryptosporidium parvum oocysts. These observations also show
      that the use of this HCT-8 cell culture assay may replace use of animal models
      for determining disinfection performances of PUV for treating both C. parvum and
      G. lamblia. 

PMID- 24929149
TI  - Immunolocalization and developmental expression patterns of two cathepsin B
      proteases (AC-cathB-1, -2) of Angiostrongylus cantonensis.
AB  - In this study we have investigated the anatomic sites of expression and
      developmental expression patterns of two cathepsin B-like cysteine proteases (AC
      cathB-1, -2) of Angiostrongylus cantonensis. The immunolocalization results
      revealed that native AC-cathBs were found present in the L1 and L3 larvae, female
      and male adults, and the AC-cathBs were localized mainly on the digestive tract
      of A. cantonensis and expressed at varied levels and in different patterns in the
      internal tissues according to their developmental stage. Consistent with the
      infective stage of L3 is a much more intense staining of AC-cathBs in the
      esophagus compared with the intestine. In contrast to L3, more abundant signals
      were located to the intestine of adults, suggesting that nutrition digestion
      likely to be the main function of the protease at this point. AC-cathBs
      fluorescent signals were present in excretory pore, excretory tube in lateral
      cords, and muscular esophagus of larvae, further supported the AC-cathB-1, -2
      likely to be released by A. cantonensis as excretory/secretory products.
      Additionally, only the protein AC-cathB-2 was detected in the reproductive
      system, especially in the wall of vas deferens, uterus, and oviduct of the
      parasites, whether the AC-cathB-2 has some function in germ cells development and
      maturation need to be further characterized. Although the anatomic sites and
      expression patterns were different in larvae and adults and the corresponding
      function might not the same, AC-cathB-1 and -2 involved in the host-parasite
      interaction in addition to digestive function. 

PMID- 24929150
TI  - Preventive and therapeutic effects of auxotrophic Edwardsiella tarda mutant
      harboring CpG 1668 motif-enriched plasmids against scuticociliatosis in olive
      flounder (Paralichthys olivaceus).
AB  - Previously generated two auxotrophic genes knockout Edwardsiella tarda (Deltaalr
      Deltaasd E. tarda) was used as a delivery vehicle for CpG 1668 motif-enriched
      plasmids (pL-CpG30), and potential of the Deltaalr Deltaasd E. tarda-mediated
      delivery of CpG motifs in both prevention and therapeutic treatment of
      scuticociliatosis caused by Miamiensis avidus in olive flounder (Paralichthys
      olivaceus) was investigated. The auxotrophic E. tarda mutant with pL-CpG30
      plasmids elicited evidently higher survival rates and delayed both onset of
      mortality and time-to-death of olive flounder against M. avidus challenge.
      Furthermore, administration of E. tarda mutant that contains plasmids enriched in
      CpG 1668 motif elicited clearly higher survival rates of fish that were already
      infected with M. avidus. These results indicate that CpG 1668 plasmids-harboring
      E. tarda mutant may provide not only preventive measure but also therapeutic
      approach against scuticociliatosis in olive flounder. 

PMID- 24929151
TI  - Bringing radiation therapy to underserved nations: an increasingly global
      responsibility in an ever-shrinking world.

PMID- 24929152
TI  - Bringing cancer care to the underserved globally: a challenging problem for which
      radiation oncology can pioneer novel solutions.

PMID- 24929153
TI  - Bringing global access to radiation therapy: time for a change in approach.

PMID- 24929154
TI  - Radiation oncology in Africa: improving access to cancer care on the African
      continent.

PMID- 24929155
TI  - Implementation of a high-dose-rate brachytherapy program for carcinoma of the
      cervix in Senegal: a pragmatic model for the developing world.
AB  - West Africa has one of the highest incidence rates of carcinoma of the cervix in
      the world. The vast majority of women do not have access to screening or disease
      treatment, leading to presentation at advanced stages and to high mortality
      rates. Compounding this problem is the lack of radiation treatment facilities in
      Senegal and many other parts of the African continent. Senegal, a country of 13
      million people, had a single (60)Co teletherapy unit before our involvement and
      no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose
      mission is to provide radiation therapy equipment to countries in the developing
      world, provided a high-dose-rate afterloading unit to the cancer center for
      curative cervical cancer treatment. Here we describe the implementation of high
      dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule
      and a novel treatment planning approach as a possible blueprint to providing this
      technology to other developing countries. 

PMID- 24929157
TI  - Cobalt, linac, or other: what is the best solution for radiation therapy in
      developing countries?
AB  - The international growth of cancer and lack of available treatment is en route to
      become a global crisis. With >60% of cancer patients needing radiation therapy at
      some point during their treatment course, the lack of available facilities and
      treatment programs worldwide is extremely problematic. The number of deaths from
      treatable cancers is projected to increase to 11.5 million deaths in 2030 because
      the international population is aging and growing. In this review, we present how
      best to answer the need for radiation therapy facilities from a technical
      standpoint. Specifically, we examine whether cobalt teletherapy machines or
      megavoltage linear accelerator machines are best equipped to handle the
      multitudes in need of radiation therapy treatment in the developing world.

PMID- 24929156
TI  - Addressing the growing cancer burden in the wake of the AIDS epidemic in
      Botswana: The BOTSOGO collaborative partnership.
AB  - Botswana has experienced a dramatic increase in HIV-related malignancies over the
      past decade. The BOTSOGO collaboration sought to establish a sustainable
      partnership with the Botswana oncology community to improve cancer care. This
      collaboration is anchored by regular tumor boards and on-site visits that have
      resulted in the introduction of new approaches to treatment and perceived
      improvements in care, providing a model for partnership between academic oncology
      centers and high-burden countries with limited resources. 

PMID- 24929158
TI  - International outreach: what is the responsibility of ASTRO and the major
      international radiation oncology societies?
AB  - In this era of globalization and rapid advances in radiation oncology worldwide,
      the American Society for Radiation Oncology (ASTRO) is committed to help decrease
      profound regional disparities through the work of the International Education
      Subcommittee (IES). The IES has expanded its base, reach, and activities to
      foster educational advances through a variety of educational methods with broad
      scope, in addition to committing to the advancement of radiation oncology care
      for cancer patients around the world, through close collaboration with our sister
      radiation oncology societies and other educational, governmental, and
      organizational groups.

PMID- 24929159
TI  - Why target the globe?: 4-year report (2009-2013) of the Association of Residents
      in Radiation Oncology Global Health Initiative.

PMID- 24929160
TI  - The medical student perspective on global health care in radiation oncology:
      opportunities, barriers to sustainability, and future directions.

PMID- 24929161
TI  - Intraoperative accelerated partial breast irradiation: caution still warranted.

PMID- 24929162
TI  - Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of
      stereotactic body radiation therapy for prostate cancer.
AB  - PURPOSE: To convey the occurrence of isolated cases of severe rectal toxicity at
      the highest dose level tested in 5-fraction stereotactic body radiation therapy
      (SBRT) for localized prostate cancer; and to rationally test potential causal
      mechanisms to guide future studies and experiments to aid in mitigating or
      altogether avoiding such severe bowel injury. METHODS AND MATERIALS: Clinical and
      treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011
      on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical
      study of SBRT for localized prostate cancer. RESULTS: At the highest dose level,
      6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of
      whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated
      with volume of rectal wall receiving 50 Gy >3 cm(3) (P<.0001), and treatment of
      >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal
      toxicity was significantly correlated with treatment of >50% circumference of
      rectal wall to 24 Gy (P=.010). CONCLUSION: Caution is advised when considering
      high-dose SBRT for treatment of tumors near bowel structures, including prostate
      cancer. Threshold dose constraints developed from physiologic principles are
      defined, and if respected can minimize risk of severe rectal toxicity.

PMID- 24929163
TI  - Impact of pretreatment tumor growth rate on outcome of early-stage lung cancer
      treated with stereotactic body radiation therapy.
AB  - PURPOSE: To determine the influence of pretreatment tumor growth rate on outcomes
      in patients with early-stage non-small cell lung cancer (NSCLC) treated with
      stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: A review was
      conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single
      institution. The patient's demographic and clinical data, time interval (t)
      between diagnostic and planning computed tomography (CT), vital status, disease
      status, and cause of death were extracted from a prospectively kept database.
      Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT
      (GTV2) were recorded, and growth rate was calculated by use of specific growth
      rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS).
      Differences between groups were compared with a log-rank test. Multivariate
      analyses were performed by use of the Cox proportional hazard model with SGR and
      other relevant clinical factors. Cumulative incidence was calculated for local,
      regional, and distant failures by use of the competing risk approach and was
      compared with Gray's test. RESULTS: The median time interval between diagnostic
      and planning CT was 82 days. The patients were divided into 2 groups, and the
      median SGR was used as a cut-off. The median survival times were 38.6 and 27.7
      months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative
      Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2
      (P=.002) were predictive for OS in multivariable Cox regression analysis and,
      except sex, were similarly predictive for failure-free survival (FFS). The 3-year
      cumulative incidences of regional failure were 19.2% and 6.0% for the high and
      low SGR groups, respectively (P=.047). CONCLUSION: High SGR was correlated with
      both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If
      validated, this measurement may be useful in identifying patients most likely to
      benefit from adjuvant therapy after SBRT.

PMID- 24929164
TI  - Neoadjuvant chemoradiation therapy using concurrent S-1 and irinotecan in rectal
      cancer: impact on long-term clinical outcomes and prognostic factors.
AB  - PURPOSE: To assess the long-term outcomes of patients with rectal cancer who
      received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and
      irinotecan (S-1/irinotecan) therapy. METHODS AND MATERIALS: The study group
      consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients
      received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan.
      The median follow-up was 60 months. RESULTS: Grade 3 adverse effects occurred in
      7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%)
      were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a
      pathological complete response (ypCR). At 60 months, the local recurrence-free
      survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS)
      was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the
      only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the
      study group as a whole. Multivariate analysis was additionally performed for the
      subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both
      ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A
      combination of these factors was very strongly related to high risk of recurrence
      (P<.0001), which occurred most commonly in the lung. CONCLUSIONS: NCRT with
      concurrent S-1/irinotecan produced high response rates and excellent long-term
      survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is
      a strong predictor of dismal outcomes, and a combination of ypT and tumor
      location can identify high-risk patients among those with ypN0/1 disease.

PMID- 24929165
TI  - Identification of patients at very low risk of local recurrence after breast
      conserving surgery.
AB  - PURPOSE: To identify clinical and pathological factors that identify groups of
      women with stage I breast cancer with a 5-year risk of local recurrence (LR)
      <=1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy
      (RT). METHODS AND MATERIALS: Study subjects were 5974 patients >=50 years of age
      whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0
      invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were
      examined using Kaplan-Meier methods. Recursive partitioning analysis was
      performed in patients treated with and without endocrine therapy to identify
      combinations of factors associated with a 5-year LR risk <=1.5%. RESULTS: The
      median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to
      91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10
      year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine
      therapy, patient subsets identified with 5-year LR <=1.5% included patients with
      grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus
      >=60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these
      groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively.
      Of 3144 patients treated without endocrine therapy, patients with grade 1
      histology plus clear margins had 5-year LR <=1.5% (n=821; LR, 0.6%; 95% CI, 0.1%
      1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). CONCLUSIONS:
      Histologic grade, age, margin status, and use of endocrine therapy identified 45%
      of a population-based cohort of female patients over age 50 with stage I breast
      cancer with a 5-year LR risk <=1.5% after BCS plus RT. Prospective study is
      needed to evaluate the safety of omitting RT in patients with such a low risk of
      LR.

PMID- 24929166
TI  - Thalidomide ameliorates inflammation and vascular injury but aggravates tubular
      damage in the irradiated mouse kidney.
AB  - PURPOSE: The late side effects of kidney irradiation include vascular damage and
      fibrosis, which are promoted by an irradiation-induced inflammatory response. We
      therefore treated kidney-irradiated mice with the anti-inflammatory and
      angiogenesis-modulating drug thalidomide in an attempt to prevent the development
      of late normal tissue damage and radiation nephropathy in the mouse kidney.
      METHODS AND MATERIALS: Kidneys of C57Bl/6 mice were irradiated with a single dose
      of 14 Gy. Starting from week 16 after irradiation, the mice were fed with
      thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and
      kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and
      40 weeks after irradiation. RESULTS: Thalidomide improved the vascular structure
      and vessel perfusion after irradiation, associated with a normalization of
      pericyte coverage. The drug also reduced infiltration of inflammatory cells but
      could not suppress the development of fibrosis. Irradiation-induced changes in
      hematocrit and blood urea nitrogen levels were not rescued by thalidomide.
      Moreover, thalidomide worsened tubular damage after irradiation and also
      negatively affected basal tubular function. CONCLUSIONS: Thalidomide improved the
      inflammatory and vascular side effects of kidney irradiation but could not
      reverse tubular toxicity, which probably prevented preservation of kidney
      function.

PMID- 24929167
TI  - How fast does real-time delivery affirmation need to be?

PMID- 24929169
TI  - Comprehensive population-averaged arterial input function for dynamic contrast
      enhanced vmagnetic resonance imaging of head and neck cancer.
AB  - PURPOSE: To generate a population-averaged arterial input function (PA-AIF) for
      quantitative analysis of dynamic contrast-enhanced MRI data in head and neck
      cancer patients. METHODS AND MATERIALS: Twenty patients underwent dynamic
      contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted
      of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of
      chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left
      carotid arteries were drawn on coronal images. Plasma concentration curves of all
      ROIs were averaged and fit to a biexponential decay function to obtain the final
      PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were
      averaged separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of
      interest were divided by time point to obtain time-point-specific AIFs
      (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (Ktrans) and the fractional
      extravascular, extracellular space volume (Ve) for primaries and nodes were
      calculated using the AvgAll AIF, the appropriate side-specific AIF, and the
      appropriate time-point-specific AIF. Median Ktrans and Ve values derived from
      AvgAll were compared with those obtained from the side-specific and time-point
      specific AIFs. The effect of using individual AIFs was also investigated.
      RESULTS: The plasma parameters for AvgAll were a1,2 = 27.11/17.65 kg/L, m1,2 =
      11.75/0.21 min(-1). The coefficients of repeatability (CRs) for AvgAll versus
      AvgLeft were 0.04 min(-1) for Ktrans and 0.02 for Ve. For AvgAll versus AvgRight,
      the CRs were 0.08 min(-1) for Ktrans and 0.02 for Ve. When AvgAll was compared
      with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min(-1),
      respectively, for Ktrans; and 0.07/0.08/0.09 for Ve. Use of a PA-AIF was not
      significantly different from use of individual AIFs. CONCLUSION: A PA-AIF for
      head and neck cancer was generated that accounts for differences in right carotid
      artery versus left carotid artery, day-to-day fluctuations, and early treatment
      induced changes. The small CRs obtained for Ktrans and Ve indicate that side
      specific AIFs are not necessary. However, a time-point-specific AIF may improve
      pharmacokinetic accuracy.

PMID- 24929168
TI  - Comparison of radiation-induced normal lung tissue density changes for patients
      from multiple institutions receiving conventional or hypofractionated treatments.
AB  - PURPOSE: To quantitatively assess changes in computed tomography (CT)-defined
      normal lung tissue density after conventional and hypofractionated radiation
      therapy (RT). METHODS AND MATERIALS: The pre-RT and post-RT CT scans from 118 and
      111 patients receiving conventional and hypofractionated RT, respectively, at 3
      institutions were registered to each other and to the 3-dimensional dose
      distribution to quantify dose-dependent changes in normal lung tissue density.
      Dose-response curves (DRC) for groups of patients receiving conventional and
      hypofractionated RT were generated for each institution, and the frequency of
      density changes >80 Hounsfield Units (HU) was modeled depending on the
      fractionation type using a Probit model for different follow-up times. RESULTS:
      For the pooled data from all institutions, there were significant differences in
      the DRC between the conventional and hypofractionated groups; the respective
      doses resulting in 50% complication risk (TD50) were 62 Gy (95% confidence
      interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51)
      versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37)
      at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46
      0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30
      (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35)
      at >12 months (P<.05 for all comparisons). CONCLUSION: Compared with conventional
      fractionation, hypofractionation has a lower TD50 and m value, both suggesting an
      increased degree of normal tissue density sensitivity with hypofractionation.

PMID- 24929170
TI  - Standardization of the target volume for boost or partial breast radiation
      therapy after lumpectomy of breast cancer.

PMID- 24929171
TI  - Dose escalation, not "new biology," can account for the efficacy of stereotactic
      body radiation therapy with non-small cell lung cancer. In regard to Brown et al.

PMID- 24929172
TI  - Dose escalation, not "new biology," can account for the efficacy of stereotactic
      body radiation therapy with non-small cell lung cancer. In reply to Rao et al.

PMID- 24929173
TI  - Occult pelvic lymph node involvement in bladder cancer: implications for
      definitive radiation. In reply to Leung.

PMID- 24929174
TI  - Occult pelvic lymph node involvement in bladder cancer: implications for
      definitive radiation. In regard to Goldsmith and Christadouleas.

PMID- 24929175
TI  - Pretreatment PET scan as a predictor of distant recurrence in non-small cell lung
      cancer. In regard to Nair et al.

PMID- 24929180
TI  - Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas
      aeruginosa escape neutrophil killing.
AB  - Pseudomonas aeruginosa is responsible for persistent infections in cystic
      fibrosis patients, suggesting an ability to circumvent innate immune defenses.
      This bacterium uses the kynurenine pathway to catabolize tryptophan.
      Interestingly, many host cells also produce kynurenine, which is known to control
      immune system homeostasis. We showed that most strains of P. aeruginosa isolated
      from cystic fibrosis patients produce a high level of kynurenine. Moreover, a
      strong transcriptional activation of kynA (the first gene involved in the
      kynurenine pathway) was observed upon contact with immune cells and particularly
      with neutrophils. In addition, using coculture of human neutrophils with various
      strains of P. aeruginosa producing no (DeltakynA) or a high level of kynurenine
      (DeltakynU or DeltakynA pkynA), we demonstrated that kynurenine promotes
      bacterial survival. In addition, increasing the amount kynurenine inhibits
      reactive oxygen species production by activated neutrophils, as evaluated by
      chemiluminescence with luminol or isoluminol or SOD-sensitive cytochrome c
      reduction assay. This inhibition is due neither to a phagocytosis defect nor to
      direct NADPH oxidase inhibition. Indeed, kynurenine has no effect on oxygen
      consumption by neutrophils activated by PMA or opsonized zymosan. Using in vitro
      reactive oxygen species-producing systems, we showed that kynurenine scavenges
      hydrogen peroxide and, to a lesser extent, superoxide. Kynurenine's scavenging
      effect occurs mainly intracellularly after bacterial stimulation, probably in the
      phagosome. In conclusion, the kynurenine pathway allows P. aeruginosa to
      circumvent the innate immune response by scavenging neutrophil reactive oxygen
      species production. 

PMID- 24929182
TI  - Men are different than women: it's true for cardiac troponin too.

PMID- 24929181
TI  - A domain analysis model for eIRB systems: addressing the weak link in clinical
      research informatics.
AB  - Institutional Review Boards (IRBs) are a critical component of clinical research
      and can become a significant bottleneck due to the dramatic increase, in both
      volume and complexity of clinical research. Despite the interest in developing
      clinical research informatics (CRI) systems and supporting data standards to
      increase clinical research efficiency and interoperability, informatics research
      in the IRB domain has not attracted much attention in the scientific community.
      The lack of standardized and structured application forms across different IRBs
      causes inefficient and inconsistent proposal reviews and cumbersome workflows.
      These issues are even more prominent in multi-institutional clinical research
      that is rapidly becoming the norm. This paper proposes and evaluates a domain
      analysis model for electronic IRB (eIRB) systems, paving the way for streamlined
      clinical research workflow via integration with other CRI systems and improved
      IRB application throughput via computer-assisted decision support. 

PMID- 24929183
TI  - Mistrust of numbers: the difficult development of psychiatric epidemiology in
      France, 1940-80.
AB  - This article uses archival as well as published materials to trace the
      development of psychiatric epidemiology in France from 1945 to 1980. Although a
      research programme in this field was launched in the early 1960s at the National
      Institute of Medical Research (INH, later renamed INSERM), psychiatric
      epidemiology remained an embryonic field in France during the next two decades.
      French researchers in this field were hampered by limited resources, but their
      work was primarily characterized by a deep engagement with the epistemological
      challenges of psychiatric epidemiology. The history of French psychiatric
      epidemiology in the 1960s and 1970s can be seen as an attempt to create a
      specifically French way of doing psychiatric epidemiology research. In the first
      part of this article, the author relates this unique history to internal
      professional dynamics during the development of psychiatric research and, more
      broadly, to the biomedical institutional context in which epidemiological work
      was being done. The next part of this article examines the conditions under which
      the INH research team framed epidemiological research in psychiatry in the 1960s.
      The last part focuses on INH's flagship psychiatric epidemiology programme,
      developed in cooperation with pioneers of French community psychiatry in Paris's
      13th arrondissement in the 1960s. 

PMID- 24929184
TI  - Consumption of both low and high (-)-epicatechin apple puree attenuates platelet
      reactivity and increases plasma concentrations of nitric oxide metabolites: a
      randomized controlled trial.
AB  - We hypothesised that consumption of flavanol-containing apple puree would
      modulate platelet activity and increase nitric oxide metabolite status, and that
      high flavanol apple puree would exert a greater effect than low flavanol apple
      puree. 25 subjects consumed 230 g of apple puree containing 25 and 100mg
      epicatechin (low and high flavanol apple puree, respectively) and aspirin (75 mg)
      in random order. Measurements were made at baseline, acutely after treatment (2,
      6 and 24 h), and after 14 d of treatment. Low flavanol apple puree significantly
      attenuated ADP and epinephrine-induced integrin-beta3 expression 2 h and 6 h
      after consumption and ADP and epinephrine-induced P-selectin expression within 2h
      of consumption. High flavanol apple puree attenuated epinephrine and ADP-induced
      integrin-beta3 expression after 2 and 6h. ADP and epinephrine-induced integrin
      beta3 expression was significantly attenuated 2, 6 and 24 h after consumption of
      aspirin, whilst 14 d aspirin consumption attenuated collagen-induced P-selectin
      expression only. The plasma total nitric oxide metabolite conc. was significantly
      increased 6h after consumption of both low and high flavanol apple purees. In
      conclusion, consumption of apple purees containing ?25 or 100 mg flavanols
      transiently attenuated ex vivo integrin-beta3 and P-selectin expression and
      increased plasma nitric oxide metabolite conc. in healthy subjects, but the
      effect was not enhanced for the high flavanol apple puree.

PMID- 24929185
TI  - The immune system, bone and RANKL.
AB  - Bone and immune systems are tightly linked. In the past years, many molecules
      originally believed to belong to the immune system were found to function in bone
      cells. It is now evident that the two systems are coregulated by many shared
      cytokines and signaling molecules. Here we exemplify the complex interaction
      between bone metabolism and immune response focusing on the multifaceted role of
      receptor activator of NF-kappaB ligand (RANKL). RANKL is expressed by cells of
      both systems, is an essential regulator of bone degradation and exerts either pro
      or anti-inflammatory effects on the immune response. In the present review, we
      summarize the multiple functions of RANKL in bone and in the immune systems,
      aiming to provide an overview of the field of osteoimmunology. 

PMID- 24929186
TI  - Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231
      human breast cancer cells by blocking beta2-adrenergic signaling.
AB  - Endogenous catecholamines such as adrenaline (A) and noradrenaline (NA) are
      released from the adrenal gland and sympathetic nervous system during exposure to
      stress. The adrenergic system plays a central role in stress signaling, and
      excessive stress was found to be associated with increased production of reactive
      oxygen species (ROS). Overproduction of ROS induces oxidative damage in tissues
      and causes the development of diseases such as cancer. In this study, we
      investigated the effects of quercetin-3-O-glucuronide (Q3G), a circulating
      metabolite of quercetin, which is a type of natural flavonoid, on the
      catecholamine-induced beta2-adrenergic receptor (beta2-AR)-mediated response in
      MDA-MB-231 human breast cancer cells expressing beta2-AR. Treatment with A or NA
      at concentrations above 1MUM generated significant levels of ROS, and NA
      treatment induced the gene expression of heme oxygenase-1 (HMOX1), and matrix
      metalloproteinase-2 (MMP-2) and -9 (MMP9). Inhibitors of p38 MAP kinase
      (SB203580), cAMP-dependent protein kinase (PKA) (H-89), activator protein-1 (AP
      1) transcription factor (SR11302), and NF-kappaB and AP-1 (Tanshinone IIA)
      decreased MMP2 and MMP9 gene expression. NA also enhanced cAMP induction, RAS
      activation and phosphorylation of ERK1/2. These results suggested that the cAMP
      PKA, MAPK, and ROS-NF-kappaB pathways are involved in beta2-AR signaling.
      Treatment with 0.1MUM Q3G suppressed ROS generation, cAMP and RAS activation,
      phosphorylation of ERK1/2 and the expression of HMOX1, MMP2, and MMP9 genes.
      Furthermore, Q3G (0.1MUM) suppressed invasion of MDA-MB-231 breast cancer cells
      and MMP-9 induction, and inhibited the binding of [(3)H]-NA to beta2-AR. These
      results suggest that Q3G may function to suppress invasion of breast cancer cells
      by controlling beta2-adrenergic signaling, and may be a dietary chemopreventive
      factor for stress-related breast cancer.

PMID- 24929187
TI  - ATM-p53 pathway causes G2/M arrest, but represses apoptosis in pseudolaric acid B
      treated HeLa cells.
AB  - Pseudolaric acid B (PAB) is a diterpene acid, isolated from the root and trunk
      bark of Pseudolarix kaempferi Gordon (Pinaceae). Previous studies demonstrated
      that PAB induced G2/M arrest and apoptosis in several cancer cell lines, but the
      relationship between G2/M arrest and apoptosis is still unclear. We examined the
      relevant signaling pathways for human cervical carcinoma HeLa cells treated with
      1 MUM PAB. Intriguingly, we found that activation of ATM-p53 signaling pathway by
      the treatment with 1 MUM PAB played a protective role for the subsequent
      apoptosis. Although the treatment with 1 MUM PAB up-regulated the expression of
      cyclin B1 and p-Histone 3 (mitotic markers) at 12 h, the expression decreased at
      24 and 36 h along with the up-down expression of mitotic markers. The expressions
      of p-ATM and p-p53 that were involved in G2/M arrest increased at 12h after
      treatment with PAB. However, a prolonged treatment with PAB (longer than 24 h)
      caused cell apoptosis. When the cells were arrested in G1 or S phase by the
      treatment with serum starvation, cytosine beta-D-arabinofuranoside (Ara-C) or
      hydroxyurea (Hu), the apoptotic ratio induced by PAB decreased.

PMID- 24929188
TI  - Shifting redox states of the iron center partitions CDO between crosslink
      formation or cysteine oxidation.
AB  - Cysteine dioxygenase (CDO) is a mononuclear iron-dependent enzyme that catalyzes
      the oxidation of L-cysteine to L-cysteine sulfinic acid. The mammalian CDO
      enzymes contain a thioether crosslink between Cys93 and Tyr157, and purified
      recombinant CDO exists as a mixture of the crosslinked and non crosslinked
      isoforms. The current study presents a method of expressing homogenously non
      crosslinked CDO using a cell permeative metal chelator in order to provide a
      comprehensive investigation of the non crosslinked and crosslinked isoforms.
      Electron paramagnetic resonance analysis of purified non crosslinked CDO revealed
      that the iron was in the EPR silent Fe(II) form. Activity of non crosslinked CDO
      monitoring dioxygen utilization showed a distinct lag phase, which correlated
      with crosslink formation. Generation of homogenously crosslinked CDO resulted in
      an ~5-fold higher kcat/Km value compared to the enzyme with a heterogenous
      mixture of crosslinked and non crosslinked CDO isoforms. EPR analysis of
      homogenously crosslinked CDO revealed that this isoform exists in the Fe(III)
      form. These studies present a new perspective on the redox properties of the
      active site iron and demonstrate that a redox switch commits CDO towards either
      formation of the Cys93-Tyr157 crosslink or oxidation of the cysteine substrate.

PMID- 24929189
TI  - Inhibition of human glutathione transferases by dinitronaphthalene derivatives.
AB  - Glutathione transferase (GST) enzymes catalyze the conjugation of glutathione
      with reactive functional groups of endogenous compounds and xenobiotics,
      including halonitroaromatics. 1-Chloro-2,4-dinitrobenzene (CDNB) is one of the
      most commonly used substrates for GST activity assays. We have studied the
      interactions of dinitronaphthalene analogues of CDNB with recombinant human GST
      enzymes (Alpha, Mu, and Pi classes) expressed in Escherichia coli.
      Dinitronaphthalene derivatives were found to be GST inhibitors. The highest
      potency of inhibition was observed towards Mu-class GSTs, M1-1 and M2-2; IC50
      values for 1-methoxy- and 1-ethoxy-2,4-dinitronaphthalene were in the high
      nanomolar to low micromolar range. Inhibition accompanies the formation, at the
      enzyme active site, of very stable Meisenheimer complex intermediates. 

PMID- 24929190
TI  - Gastric bypass patients' goal-strategy-monitoring networks for long-term dietary
      management.
AB  - Following gastric bypass surgery, patients must make dramatic dietary changes,
      but little is known about patients' perspectives on long-term dietary management
      after this surgery. This grounded theory, qualitative study sought to advance
      conceptual understanding of food choice by examining how gastric bypass patients
      constructed personal food systems to guide food and eating behaviors 12 months
      post-surgery. Two in-depth interviews were conducted with each of 16 adults,
      purposively sampled from bariatric support groups. Using constant comparative
      analysis of verbatim interview transcripts, researchers identified participants'
      goal-strategy-monitoring networks representing how participants used specific
      food and eating behaviors towards their main goals of: Weight Management, Overall
      Health, Avoiding Negative Reactions to Eating, and Integrating Dietary Changes
      with Daily Life. Linked to each main goal was a hierarchy of intermediary goals,
      strategies, and tactics. Participants used monitoring behaviors to assess
      strategy effectiveness towards goal achievement. Individuals' Weight Management
      networks were compared to uncover similarities and differences among strategy use
      and monitoring methods among those who maintained weight loss and those who
      regained weight. The complex, multilevel goal-strategy-monitoring networks
      identified illustrate the "work" involved in constructing new personal food
      systems after surgery, as well as advance understanding of strategies as a
      component of people's personal food systems. These findings provide researchers
      and practitioners with insight into the long-term dietary issues that gastric
      bypass patients face and a potential method for representing how people relate
      deliberate dietary behaviors to their goals. 

PMID- 24929191
TI  - Liking the odour, liking the food. Toddlers' liking of strongly flavoured foods
      correlates with liking of their odour.
AB  - Olfaction plays a significant role in the sensing of foods. However, little
      information is available at any age on the relationship between the hedonic
      responses to given food odours and the effective liking and disliking of foods
      bearing these same odours. The present study aimed to assess the relationships
      between food odour liking and liking of the corresponding foods. This study
      relied on a longitudinal design involving 235 toddlers who were assessed for both
      their observed liking of a set of food odours and their parent-reported liking of
      foods at 12 and 22 months. To assess odour liking, eight odorants representing
      pleasant and unpleasant foods were presented in bottles along with neutral
      stimuli. The participants' behaviour towards the odorized and control bottles was
      measured in terms of mouthing, a behaviour considered to reflect attraction. For
      each odorant, odour-liking scores were calculated relative to the control. The
      participants' food liking was rated by the parents at the periods 12-15 and 21-24
      months. Positive correlations were found between the odour-liking scores for some
      of the odours and the liking of the associated foods. These correlations
      concerned foods with strong, unpleasant flavours at 12 months only, suggesting
      that the olfactory system acts as an 'alarm' system during this period of food
      transition. At 22 months, no significant correlations were found, except a
      marginal one for green vegetables. Whatever the age, no significant correlations
      were found for pleasant odours. Thus, some correlations were found between the
      observed odour liking for food-related odours and the liking for the
      corresponding foods. However, these relationships are subject to developmental
      fluctuations depending on the hedonic nature of the odorants and the age when
      infants are tested. 

PMID- 24929192
TI  - Kinetic characteristics of euflammation: the induction of controlled inflammation
      without overt sickness behavior.
AB  - We found recently that controlled progressive challenge with subthreshold levels
      of E. coli can confer progressively stronger resistance to future reinfection
      induced sickness behavior to the host. We have termed this type of inflammation
      "euflammation". In this study, we further characterized the kinetic changes in
      the behavior, immunological, and neuroendocrine aspects of euflammation. Results
      show euflammatory animals only display transient and subtle sickness behaviors of
      anorexia, adipsia, and anhedonia upon a later infectious challenge which would
      have caused much more severe and longer lasting sickness behavior if given
      without prior euflammatory challenges. Similarly, infectious challenge-induced
      corticosterone secretion was greatly ameliorated in euflammatory animals. At the
      site of E.coli priming injections, which we termed euflammation induction locus
      (EIL), innate immune cells displayed a partial endotoxin tolerant phenotype with
      reduced expression of innate activation markers and muted inflammatory cytokine
      expression upon ex vivo LPS stimulation, whereas innate immune cells outside EIL
      displayed largely opposite characteristics. Bacterial clearance function,
      however, was enhanced both inside and outside EIL. Finally, sickness induction by
      an infectious challenge placed outside the EIL was also abrogated. These results
      suggest euflammation could be used as an efficient method to "train" the innate
      immune system to resist the consequences of future infectious/inflammatory
      challenges. 

PMID- 24929193
TI  - C-reactive protein and depression in persons with Human Immunodeficiency Virus
      infection: the Positive Living with HIV (POLH) Study.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) infection has been frequently
      associated with chronic inflammation as well as depression. C-reactive protein
      (CRP) is positively associated with depression in people without HIV infection.
      We tested the hypothesis of an independent relationship between CRP and
      depression in a cohort of HIV-positive people. METHODS: A cross-sectional survey
      was conducted among 316 HIV-positive people (181 men and 135 women) aged 18
      60years residing in the Kathmandu Valley, Nepal. The latex agglutination
      turbidimetric method was used to measure serum CRP concentrations and the Beck
      Depression Inventory (BDI)-I method was used to measure depression, with a cut
      off of ?20 indicating likely depression. The relationship between CRP
      concentrations and depression symptoms was assessed using both multiple linear
      regression analysis and multiple logistic regression analysis, with adjustment
      for potential socio-demographic, cardiovascular, life-style, and HIV-related
      clinical and treatment confounding factors. RESULTS: Twenty-six percent
      participants (men: 23%; women: 29%) met criteria for depression. In multiple
      regression analysis, the authors observed a linear relation between serum CRP
      concentrations and BDI score (beta for 1 unit change in ln(CRP)=1.13, p=0.001) in
      HIV-positive participants. In a logistic regression analysis, participants with
      serum CRP levels>3mg/L had a 2.3-fold higher odds of depression symptoms compared
      to those with serum CRP level?3mg/L (p=0.005). In analyses stratified by sex,
      associations were stronger in men than in women. For example, CRP>3mg/L was
      associated with a 3.6-fold higher odds of depression in men (p=0.002), while in
      women the odds ratio was 1.7 (p=0.33). CONCLUSION: We found a linear relationship
      between serum CRP concentrations and depression symptoms score in HIV-positive
      people, and evidence that risk of depression is elevated among HIV-positive men
      with a high level of inflammation (CRP>3mg/L). Further prospective study to
      confirm the role of inflammation in depression among HIV-positive people is
      warranted.

PMID- 24929194
TI  - Cohabitation with a sick partner increases allergic lung inflammatory response in
      mice.
AB  - The bidirectional relationship between the nervous system and the immune system
      is relevant for homeostatic organism maintenance. Studies from our laboratory
      showed that 14days of cohabitation with a sick partner (injected with Ehrlich
      tumor cells-TAE) produced behavioral, neurochemical, endocrinological and
      immunological changes. This study analyzes the effects of cohabitation with an
      Ehrlich tumor-bearing animal on ovalbumin (OVA)-induced lung inflammatory
      response in mice. Pairs of male mice were divided into three groups: naive,
      control and experimental. Animals of the naive group were kept undisturbed being
      used for the assessment of basal parameters. One animal of each experimental and
      control pair of mice was immunized with OVA. On ED(0), these OVA-immunized
      animals received an OVA booster. At this day (D(0)) the experimental mice that
      were kept undisturbed were inoculated with 5*10(6) Ehrlich tumor cells; their
      immunized cage-mates were then referred as to CSP ("companion of sick partner").
      The undisturbed mice of each control pair were i.p. treated on D(0) with 0.9%
      NaCl; their sensitized cage-mates were subsequently referred as CHP ("companion
      of health partner"). The OVA challenge was performed on CSP and CHP mice on
      ED(12) and ED(13); blood and tissue collection were performed on ED(14). Fourteen
      days after cohabitation, in comparison to the CHP mice, the CSP mice displayed
      the following: (1) an increased number of eosinophils and neutrophils in the BAL,
      (2) a decreased bone marrow cell count, (3) increased levels of IL-4 and IL-5 and
      decreased levels of IL-10 and IFN-gamma in the BAL supernatant, (5) increased
      levels of IgG1-OVA, decreased levels of IgG2a-OVA and no changes in OVA-specific
      IgE in the peripheral blood, (6) increased expression of L-selectin in the BAL
      granulocytes, (7) decreased tracheal reactivity to methacholine measured in
      vitro, (8) no changes in plasma corticosterone levels and (9) increased levels of
      plasmatic noradrenaline. These results suggest that allergic lung inflammatory
      response exacerbation in CSP mice is a consequence of the psychological stress
      induced by forced cohabitation with the sick partner. Strong involvement of the
      sympathetic nervous system (SNS) through adrenaline and noradrenaline release and
      a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to
      be the mechanisms underlying the cell recruitment to the animal's airways. 

PMID- 24929195
TI  - Proinflammatory milieu in combat-related PTSD is independent of depression and
      early life stress.
AB  - BACKGROUND: Chronic inflammation may be involved in combat-related post-traumatic
      stress disorder (PTSD) and may help explain comorbid physical diseases. However,
      the extent to which combat exposure per se, depression, or early life trauma, all
      of which are associated with combat PTSD, may confound the relationship between
      PTSD and inflammation is unclear. METHODS: We quantified interleukin (IL)-6, IL
      1beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and C-reactive
      protein (CRP) in 51 combat-exposed males with PTSD and 51 combat-exposed males
      without PTSD, and assessed PTSD and depression severity as well as history of
      early life trauma. To decrease the possibility of Type I errors, we summed
      standardized scores of IL-1beta, IL-6, TNFalpha, IFNgamma and CRP into a total
      "pro-inflammatory score". PTSD symptom severity was assessed with the Clinician
      Administered PTSD Scale (CAPS) rating scale. RESULTS: Subjects with PTSD had
      significantly higher pro-inflammatory scores compared to combat-exposed subjects
      without PTSD (p=0.006), and even after controlling for early life trauma,
      depression diagnosis and severity, body mass index, ethnicity, education,
      asthma/allergies, time since combat and the use of possibly confounding
      medications (p=0.002). Within the PTSD group, the pro-inflammatory score was not
      significantly correlated with depressive symptom severity, CAPS total score, or
      with the number of early life traumas. CONCLUSIONS: Combat-related PTSD in males
      is associated with higher levels of pro-inflammatory cytokines, even after
      accounting for depression and early life trauma. These results, from one of the
      largest studies of inflammatory cytokines in PTSD to date, suggest that immune
      activation may be a core element of PTSD pathophysiology more so than a signature
      of combat exposure alone.

PMID- 24929196
TI  - Driving towards obesity: a systematized literature review on the association
      between motor vehicle travel time and distance and weight status in adults.
AB  - BACKGROUND: Higher levels of sedentary behavior are associated with adverse
      health outcomes. Over-reliance on private motor vehicles for transportation is a
      potential contributor to the obesity epidemic. The objective of this study was to
      review evidence on the relationship between motor vehicle travel distance and
      time and weight status among adults. METHODS: Keywords associated with driving
      and weight status were entered into four databases (PubMed Medline Transportation
      Research Information Database and Web of Science) and retrieved article titles
      and abstracts screened for relevance. Relevant articles were assessed for their
      eligibility for inclusion in the review (English-language articles a sample >= 16
      years of age included a measure of time or distance traveling in a motor vehicle
      and weight status and estimated the association between driving and weight
      status). RESULTS: The database search yielded 2781 articles, from which 88 were
      deemed relevant and 10 studies met the inclusion criteria. Of the 10 studies
      included in the review, 8 found a statistically significant positive association
      between time and distance traveled in a motor vehicle and weight status.
      CONCLUSIONS: Multilevel interventions that make alternatives to driving private
      motor vehicles more convenient, such as walking and cycling, are needed to
      promote healthy weight in the adult population.

PMID- 24929197
TI  - Association between perceived urban built environment attributes and leisure-time
      physical activity among adults in Hangzhou, China.
AB  - BACKGROUND: Neighborhood built environment may influence residents' physical
      activity, which in turn, affects their health. This study aimed to determine the
      associations between perceived built environment and leisure-time physical
      activity in Hangzhou, China. METHODS: 1440 participants aged 25-59 were randomly
      selected from 30 neighborhoods in three types of administrative planning units in
      Hangzhou. International Physical Activity Questionnaire long form and NEWS-A were
      used to obtain individual-level data. The China Urban Built Environment Scan Tool
      was used to objectively assess the neighborhood-level built environment. Multi
      level regression was used to explore the relationship between perceived built
      environment variables and leisure-time physical activities. Data was collected in
      Hangzhou from June to December in 2012, and was analyzed in May 2013. RESULTS:
      Significant difference between neighborhood random variations in physical
      activity was identified (P=0.0134); neighborhood-level differences accounted for
      3.0% of the variability in leisure-time physical activity. Male residents who
      perceived higher scores on access to physical activity destinations reported more
      involvement in leisure-time physical activity. Higher scores on perception of
      esthetic quality, and lower on residential density were associated with more time
      in leisure-time walking in women. CONCLUSIONS: The present study demonstrated
      that perceived urban built environment attributes significantly correlate with
      leisure-time physical activity in Hangzhou, China.

PMID- 24929198
TI  - Reply to letter: False positive absent somatosensory evoked potentials in cardiac
      arrest with therapeutic hypothermia.

PMID- 24929199
TI  - Post-resuscitation electrocardiograms, acute coronary findings and in-hospital
      prognosis of survivors of out-of-hospital cardiac arrest.
AB  - BACKGROUND: Identification of acute coronary lesions amenable to urgent
      intervention in survivors of out-of-hospital cardiac arrest is crucial. We aimed
      to compare the clinical and electrocardiographic characteristics to urgent
      coronary findings, and to analyze in-hospital prognosis of these patients.
      METHODS: From January 2005 to December 2012 we retrospectively identified
      consecutive patients resuscitated from out-of-hospital cardiac arrest, and
      analyzed the clinical characteristics, post-resuscitation electrocardiogram and
      coronary angiogram of those who underwent emergent angiography. Mortality and
      neurologic status at discharge were also assessed. RESULTS: Patients with ST
      elevation more frequently had obstructive coronary artery disease (89% vs. 51%,
      p<0.001) or acute coronary occlusions (83% vs. 8%, p<0.001) than patients without
      ST-elevation. Independent predictors of an acute coronary occlusion were chest
      pain before arrest (OR 0.16, 95% CI 0.04-0.7, p=0.01), a shockable initial rhythm
      (OR 0.16, 95% CI 0.03-0.9, p=0.03), and ST-elevation on the post-resuscitation
      electrocardiogram (OR 0.02, 95% CI 0.004-0.13, p<0.001). Survival with favorable
      neurologic recovery at discharge was 59%. Independent predictors of mortality or
      unfavorable neurological outcome at discharge were absence of basic life support
      (OR 0.2, 95% CI 0.06-0.9, p=0.04), prolonged resuscitation time (OR 0.9, 95% CI
      0.8-0.9, p=0.01), and necessity of vasopressors (OR 14.8, 95% CI 3.3-65.4,
      p=0.001). CONCLUSIONS: Most patients with ST-elevation on the post-resuscitation
      electrocardiogram had an acute coronary occlusion, as opposed to patients without
      ST-elevation. Absence of basic life support, prolonged resuscitation time and use
      of vasopressors were independent predictors of worse in-hospital outcome.

PMID- 24929200
TI  - Efficient extracellular production of kappa-carrageenase in Escherichia coli:
      effects of wild-type signal sequence and process conditions on extracellular
      secretion.
AB  - Signal peptides direct proteins to translocate across the bacterial cytoplasmic
      membrane. This study aimed to improve the level of extracellular secretion of
      recombinant carrageenase by recombining the gene encoding wild-type signal
      peptide (OmpZ) of Zobellia sp. ZM-2 kappa-carrageenase into the expression vector
      pProEX-HTa-cgkZ. The recombinant strain BL21-HTa-cgkZ achieved extracellular
      secretion of kappa-carrageenase. The effects of induction, culture conditions,
      and additives were investigated to further promote the extracellular secretion of
      the enzyme. Results showed that the wild-type signal sequence secreted
      recombinant kappa-carrageenase out of the cytoplasmic membrane. Low temperature
      (23  degrees C) and optimum isopropyl-beta-thiogalactoside concentration (0.9 mM)
      favored soluble protein expression. Moreover, additives such as lactose, glycine,
      Tween-80, and TritonX-100 promoted the release of intracellular enzymes. The
      existence of OmpZ resulted in 51% of the total kappa-carrageenase accumulation
      secreted into culture medium, and 33% accumulated in the periplasmic space. High
      extracellular secretion of recombinant kappa-carrageenase under the optimum
      conditions showed promising applications of the process for extracellular protein
      production.

PMID- 24929201
TI  - Investigating socio-cognitive processes in deception: a quantitative meta
      analysis of neuroimaging studies.
AB  - Recent neuroimaging studies have found a broad network of brain regions involved
      in deception, including the prefrontal cortex, insula, anterior cingulate cortex
      (ACC), and inferior parietal lobule (IPL). Although deception can be
      conceptualized as the attempt to deliberately cause another person to accept a
      false belief, research to date has mainly focused on executive control processes
      when participants are instructed to lie under certain conditions. Recently, more
      ecologically valid and interactive experimental paradigms have been used in which
      subjects were also requested to take the perspective of another person, read his
      or her intentions, and make a self-determined decision to deceive that person and
      break a moral rule. To investigate the influence of these socio-cognitive
      processes on the neural network of deception, we performed a quantitative meta
      analysis combining the data from 416 participants across 22 fMRI and two PET
      studies. Based on the description of the experimental paradigm, studies were
      divided in social interactive and non-interactive deception studies. Increased
      activation in the dorsal ACC, the right temporo-parietal junction (TPJ)/angular
      gyrus, and the bilateral temporal pole (TP) was found to be greater in social
      interactive than in non-interactive deception. These results demonstrate the
      important role of perspective taking, theory of mind, and moral reasoning
      processes in deception as well as conflict processing. In addition to the role of
      executive control processes determined by previous meta-analyses, our findings
      show the importance of these socio-cognitive processes in deception and give new
      insight into the function and interpretation of the brain regions involved.

PMID- 24929202
TI  - EBI3 is pivotal for the initiation of experimental autoimmune uveitis.
AB  - Murine experimental autoimmune uveitis (EAU) is a model for human autoimmune
      uveitis, whose pathogenesis is caused by both Th1 and Th17 cell responses.
      Epstein-Barr virus-induced gene 3 (EBI3) is a component of the heterodimeric
      cytokines: interleukin (IL)-27 and IL-35. Although IL-27 was shown to initiate
      Th1 cell development, it is also recognized as a negative regulator of fully
      activated CD4+ T cells, including Th17 cells. Recently, IL-35 also has also been
      reported to play immunosuppressive roles in autoimmunity. To investigate the
      roles of EBI3 in EAU, EBI3(-/-) mice were immunized with human interphotoreceptor
      retinoid binding protein peptide 1-20 (IRBP) to induce EAU. We observed that the
      clinical score in EBI3(-/-) mice was diminished compared with that in EBI3(+/+)
      mice up to day 22 after immunization, whereas the score in EBI3(-/-) mice reached
      the same levels as that of EBI3(+/+) mice after day 28. Histological analysis
      revealed a significant reduction of cellular infiltration into the retina in
      EBI3(-/-) mice on day 16. Although Th1 cell responses and IRBP-specific IL-10
      production were reduced in EBI3(-/-) mice, the development of Th17 cell responses
      was unaffected on day 9. On day 21, Th1 cell responses and IRBP-specific IL-10
      production was restored to the same levels as that in EBI3(+/+) mice, and Th17
      cell responses significantly increased in EBI3(-/-) mice. Furthermore, Foxp3
      expression in CD4+ T cells was comparable between EBI3(+/+) and EBI3(-/-) mice on
      days 9 and 21. Therefore, these results indicate that EBI3 may be important in
      EAU initiation by Th1 cell responses and may suppress EAU by inhibition of both
      Th1 and Th17 cell responses in the late/maintenance phase.

PMID- 24929204
TI  - Mechanical and structural properties of bone in non-critical and critical healing
      in rat.
AB  - A fracture in bone results in a dramatic change of mechanical loading conditions
      at the site of injury. Usually, bone injuries heal normally but with increasing
      fracture gaps, healing is retarded, eventually leading to non-unions. The
      clinical situation of these two processes with different outcomes is well
      described. However, the exact relation between the mechanical environment and
      characteristics of the tissues at all levels of structural hierarchy remains
      unclear. Here we studied the differences in material formation of non-critical
      (1mm) and critical (5mm gap) healing. We employed a rat osteotomy model to
      explore bone material structure depending upon the different mechanical
      conditions. In both cases, primary bone formation was followed by secondary bone
      deposition with mineral particle sizes changing from on average short and thick
      to long and thin particles. Bony bridging occurred at first in the endosteal
      callus and the nanostructure and microstructure developed towards cortical
      ordered material organization. In contrast, in critical healing, instead of
      bridging, a marrow cavity closure was formed endosteal, exhibiting tissue
      structure oriented along the curvature and a periosteal callus with less mature
      material structure. The two healing processes separated between 4 and 6 weeks
      post-osteotomy. The outcome of healing was determined by the varied geometrical
      conditions in critical and non-critical healing, inducing completely different
      mechanical situations.

PMID- 24929203
TI  - BAC-EDTA transepithelial riboflavin-UVA crosslinking has greater biomechanical
      stiffening effect than standard epithelium-off in rabbit corneas.
AB  - Studies suggest that standard corneal collagen crosslinking (CXL) is a safe and
      effective treatment to stiffen the cornea for keratoconus and other ectatic
      corneal disorders. The purpose of the present study was to compare the
      biomechanical effects of transepithelial benzalkonium chloride-EDTA (BAC-EDTA)
      riboflavin-UVA crosslinking to standard epithelium-off riboflavin-UVA
      crosslinking in a rabbit model. Corneal stiffness was quantified using optical
      coherence elastography at two months after treatment. The mean lateral-to-axial
      displacement ratio for the BAC-EDTA transepithelial CXL group was lower (greater
      stiffness) [0.062 +/- 0.042, mean +/- SD] than epithelium-off CXL (mean +/- SD:
      0.065 +/- 0.045) or untreated control eyes (0.069 +/- 0.044). Using ANOVA with
      Tukey correction, a statistically significant difference was found between the
      BAC-EDTA transepithelial CXL group and standard epithelium-off CXL (p = 0.0019)
      or the untreated control (p < 0.0001) groups. A graph of the probability density
      functions for biomechanical stiffness also showed a greater shift in stiffening
      in the BAC-EDTA transepithelial CXL group than the standard epithelium-off CXL or
      untreated control group. These results demonstrated that the biomechanical
      stiffening effect produced by BAC-EDTA transepithelial CXL was greater than that
      produced by standard epithelium-off CXL in a rabbit model. 

PMID- 24929205
TI  - Clinical relevance of urinary angiotensinogen and renin as potential biomarkers
      in patients with overt proteinuria.
AB  - Urinary angiotensinogen (AGT) and renin have been reported to reflect the
      intrarenal renin-angiotensin system (RAS) activity. However, the adequacy and
      clinical significance of these markers have not been evaluated in overtly
      proteinuric patients. In patients with biopsy-proven glomerulonephritis, plasma
      and urinary AGT and renin were analyzed. A cohort of 75 patients treated with RAS
      inhibitors was followed for 1 year. Among the 207 patients, 105 had subnephrotic
      and 102 had nephrotic-range proteinuria. Mean age, estimated glomerular
      filtration rate (eGFR), and urinary protein-to-creatinine ratio (P/Cr) of all
      patients were 48 years, 79.7 mL/min/1.73 m(2), and 5.66 mg/mg, respectively. Both
      natural logarithm of urinary AGT/creatinine (ln [urinary AGT/Cr]) and ln (urinary
      renin/Cr) showed positive correlations with urinary P/Cr. There was a positive
      correlation between ln (urinary AGT/Cr) and ln (urinary renin/Cr). Ln (urinary
      renin/Cr) was not affected by ln (plasma renin) regardless of the degree of
      proteinuria. The treatment response to RAS inhibitors was greatest in patients
      with high urinary AGT and renin. However, the predictive value of those
      parameters was no longer present when the values were adjusted by the degree of
      proteinuria. Ln (urinary renin/Cr) and initial eGFR were independently associated
      with the changes in renal function for 1 year. Ln (urinary AGT/Cr) was associated
      with persistent overt proteinuria after 1 year. Our study suggests that urinary
      renin may be a better marker in heavy proteinuria, and the treatment response to
      RAS inhibitors may be enhanced in patients with high urinary renin and AGT.
      Further studies will be necessary to explore the value of urinary AGT and renin. 

PMID- 24929206
TI  - Adipose tissue changes in obesity and the impact on metabolic function.
AB  - Obesity is associated with adverse alterations in adipose tissue that predispose
      to metabolic dysregulation. These adverse alterations include accumulation of
      inflammatory macrophages leading to the activation of inflammation pathways,
      reduction in lipid turnover, and deposition of fat in ectopic locations. These
      alterations are precursors to the development of insulin resistance and metabolic
      dysfunction. 

PMID- 24929207
TI  - The genetics of human obesity.
AB  - The heritability of obesity has long been appreciated and the genetics of obesity
      has been the focus of intensive study for decades. Early studies elucidating
      genetic factors involved in rare monogenic and syndromic forms of extreme obesity
      focused attention on dysfunction of hypothalamic leptin-related pathways in the
      control of food intake as a major contributor. Subsequent genome-wide association
      studies of common genetic variants identified novel loci that are involved in
      more common forms of obesity across populations of diverse ethnicities and ages.
      The subsequent search for factors contributing to the heritability of obesity not
      explained by these 2 approaches ("missing heritability") has revealed additional
      rare variants, copy number variants, and epigenetic changes that contribute.
      Although clinical applications of these findings have been limited to date, the
      increasing understanding of the interplay of these genetic factors with
      environmental conditions, such as the increased availability of high calorie
      foods and decreased energy expenditure of sedentary lifestyles, promises to
      accelerate the translation of genetic findings into more successful preventive
      and therapeutic interventions.

PMID- 24929208
TI  - Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via
      tunneling nanotubes.
AB  - Tunneling nanotubes (TnTs) represent a novel mechanism by which intercellular
      components such as proteins, Golgi vesicles, and mitochondria can be transferred
      from cell to cell in the complex tumor microenvironment. Here, we report data
      showing that microRNAs (miRNAs) are transferred through TnTs in osteosarcoma (OS)
      and ovarian cancer as in vitro model systems. miRNA array analysis demonstrated
      significant upregulation of miR-19a in OS tumors resected from human patients,
      and differential expression of miR-199a in ovarian cancer cell lines resistant or
      sensitive to platinum chemotherapy. K7M2 murine OS cells were transfected with
      miR-19a and cultured with nontransfected K7M2 cells in low-serum, hyperglycemic
      medium for up to 72 hours to induce TnT formation. miRNA transfer via TnTs was
      detected by time-lapse microscopic imaging. miR-19a was also transported via TnTs
      connecting transfected K7M2 cells and nontransfected stromal MC3T3 murine
      osteoblast cells. Similar findings were observed in studies of TnT-mediated
      transport of miR-199a among SKOV3 ovarian cancer cells and nonmalignant
      immortalized ovarian epithelial cells. To quantify TnT-mediated transport of
      miRNAs, we used modified Boyden chambers to separate miR-19a-transfected K7M2
      cells (top chamber) and DiI-labeled MC3T3 cells (bottom chamber) compared with
      open culture of these cells. Fluorescence-activated cell sorting analysis of
      cells collected after 48 hours of culture indicated that miR-19a-positive MC3T3
      cells were 3-fold higher in open culture; this finding suggests that miR-19a
      transfer occurred via TnTs, exclusive of other forms of cell-cell communication.
      These studies demonstrate that TnTs mediate direct transfer of genetic material
      between tumor and stromal cells. 

PMID- 24929210
TI  - Release behavior and antibiofilm activity of usnic acid-loaded carboxylated
      poly(L-lactide) microparticles.
AB  - The use of controlled drug delivery systems could give a significant contribution
      to the improvement of therapies against biofilm-based infections. The aim of this
      study was to develop polymer microparticles, based on carboxylated poly(L
      lactide)s, to be employed as carriers for usnic acid (UA), a poorly soluble drug
      possessing antiviral, antiproliferative and wide spectrum antimicrobial activity.
      Thanks to polymer surfactant-like structure, 2.4 MUm-in-size microparticles were
      obtained by a surfactant-free oil-in-water emulsion/evaporation method. UA was
      encapsulated into these microparticles with a high loading efficiency (80%). The
      drug release kinetics was found to be temperature dependent (the released dose
      increasing with temperature) and showed bimodal release behavior. By polarized
      optical microscopy observations and the application of kinetics models, the
      initial burst effect was attributed to the delivery of the drug amorphous
      fraction while the slower release occurring for longer times to the crystalline
      one, both entrapped in the polymer amorphous phase. UA-loaded microparticles were
      able to promote the killing of a 24h-old Staphylococcus epidermidis biofilm more
      efficaciously than free UA.

PMID- 24929209
TI  - Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus
      and cortex after traumatic brain injury.
AB  - After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1
      produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3
      produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative
      importance of caspase-dependent apoptosis or calpain-dependent
      excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat,
      controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting
      a few days, and increased 145 SBDPs within the first few days lasting up to 14
      days after injury. Little is known about SBDPs in the immature brain after TBI.
      Since development affects susceptibility to apoptosis after TBI, we hypothesized
      that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to
      SHAM during the first 3 and 5 days, respectively. SBDPs were measured in
      hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI
      or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both
      brain tissues ipsilateral to injury during the first 3 days, while changes in
      contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more
      marked and enduring in hippocampus than in cortex. Against expectations, 120
      SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations
      occurred early after CCI, similar to previous studies in the adult rat, but
      resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain
      dependent, but not caspase-dependent, cell death predominates in the 17 day old
      rat after CCI. 

PMID- 24929211
TI  - Tablets of pre-liposomes govern in situ formation of liposomes: concept and
      potential of the novel drug delivery system.
AB  - The purpose of this study was to develop a novel drug delivery system for
      challenging drugs with potential for scale-up manufacturing and controlled
      release of incorporated drug. Pre-liposomes powder containing metronidazole,
      lecithin and mannitol, prepared by spray-drying, was mixed with different
      tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol,
      dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and
      compressed into tablets. The delivery system was characterized with respect to
      (i) dry powder characteristics, (ii) mechanical tablet properties and drug
      release, and (iii) liposomal characteristics. The pre-liposomes powder was free
      flowing, and tablets of similarly high qualities as tablets made of physical
      mixtures were prepared with all excipients. Liposomes were formed in situ upon
      tablet disintegration, dissolution or erosion depending on the type of tablet
      excipient used. The liposomal characteristics and drug release were found to
      depend on the tablet excipient. The new delivery system offers a unique synergy
      between the ability of liposomes to encapsulate and protect drugs and increased
      stability provided by compressed formulations. It can be adjusted for drug
      administration via various routes, e.g. oral, buccal and vaginal. 

PMID- 24929212
TI  - Polymersomes conjugated to 83-14 monoclonal antibodies: in vitro targeting of
      brain capillary endothelial cells.
AB  - The blood-brain barrier (BBB) remains an obstacle for many drugs to reach the
      brain. A strategy to cross the BBB is to modify nanocarrier systems with ligands
      that bind to endogenous receptors expressed at the BBB to induce receptor
      mediated transport. The aim of the present study was to investigate the potential
      of polymersomes composed of the amphiphilic diblock copolymer
      poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline), PDMS-b-PMOXA, for active
      targeting of brain capillary endothelial cells. We conjugated PDMS-b-PMOXA
      polymersomes to the anti-human insulin receptor antibody 83-14 and studied their
      uptake by brain capillary endothelial cells. Transmission electron micrography
      and light scattering measurements revealed the self-assembly of the block
      copolymers into 200 nm vesicles after extrusion. Fluorescence correlation
      spectroscopy was employed to calculate the number of antibodies coupled to one
      polymersome. Binding and uptake of the polymersomes conjugated to 83-14 mAb were
      studied in the human BBB in vitro model hCMEC/D3 expressing the human insulin
      receptor. Competitive inhibition with an excess of free 83-14 mAb demonstrated
      the specificity of cellular binding and uptake. Our results suggest that PDMS-b
      PMOXA polymersomes conjugated to 83-14 mAb may be suitable nanocarriers for drug
      delivery to the brain.

PMID- 24929213
TI  - Chronic arthritis in a boy with Cernunnos immunodeficiency.

PMID- 24929214
TI  - Hydrogen sulfide and nitric oxide interactions in inflammation.
AB  - Together with carbon monoxide (CO), nitric oxide (NO) and hydrogen sulfide (H2S)
      form a group of physiologically important gaseous transmitters, sometimes
      referred to as the "gaseous triumvirate". The three molecules share a wide range
      of physical and physiological properties: they are small gaseous molecules, able
      to freely penetrate cellular membranes; they are all produced endogenously in the
      body and they seem to exert similar biological functions. In the cardiovascular
      system, for example, they are all vasodilators, promote angiogenesis and protect
      tissues against damage (e.g. ischemia-reperfusion injury). In addition, they have
      complex roles in inflammation, with both pro- and anti-inflammatory effects
      reported. Researchers have focused their efforts in understanding and describing
      the roles of each of these molecules in different physiological systems, and in
      the past years attention has also been given to the gases interaction or "cross
      talk". This review will focus on the role of NO and H2S in inflammation and will
      give an overview of the evidence collected so far suggesting the importance of
      their cross-talk in inflammatory processes. 

PMID- 24929215
TI  - Wolbachia translation initiation factor-1 is copiously expressed by the adult,
      microfilariae and infective larvae of Brugia malayi and competitively inhibited
      by tetracycline.
AB  - The intracellular alphaproteobacteria, Wolbachia, is considered to be a future
      antimacrofilarial drug target as it is obligatory for filarial endurance.
      Characterizing wolbachial proteins is necessary to understand wolbachial
      mechanisms and also for discovering new drug entities. Translation initiation
      factor-1 (Tl IF-1) is an indispensable prokaryotic factor concerned with
      bacterial viability. This factor is prioritized as one of the most potent
      antibacterial drug target. To investigate its role in filarial biology,
      recombinant Wol Tl IF-1 was purified on metal ion column. The factor was found
      folded in its monomeric native conformation, and contained a buried fluorophore.
      Molecular modeling revealed that the factor belonged to the Oligomer Binding
      family, and consisted of the highly conserved S1 domain with 81.6% of the amino
      acids occupying the allowed regions in Ramachandran plot. In addition, Wol Tl IF
      1 exhibited selective binding to the 30S ribosomal subunit, which declined
      progressively with tetracycline addition. Tetracycline perturbs interaction of
      Thr18 and Asn32 of the factor with ribosomal protein S4. The factor was immune
      localized in adult, microfilariae (Mf) and infective larvae (L3) of Brugia malayi
      by immunoblotting. High expression was also observed in Wolbachia within B.
      malayi Mf, L3 and female adult parasite along the gravid uteri by the confocal
      microscopy. Therefore, Wol Tl IF-1 appears to be an essential Wolbachia factor
      whose inhibition leads to extensive cell apoptosis and premature killing of adult
      worms, validating the antifilarial potential of the factor. 

PMID- 24929216
TI  - Comprehensive review on lactate metabolism in human health.
AB  - Metabolic pathways involved in lactate metabolism are important to understand the
      physiological response to exercise and the pathogenesis of prevalent diseases
      such as diabetes and cancer. Monocarboxylate transporters are being investigated
      as potential targets for diagnosis and therapy of these and other disorders.
      Glucose and alanine produce pyruvate which is reduced to lactate by lactate
      dehydrogenase in the cytoplasm without oxygen consumption. Lactate removal takes
      place via its oxidation to pyruvate by lactate dehydrogenase. Pyruvate may be
      either oxidized to carbon dioxide producing energy or transformed into glucose.
      Pyruvate oxidation requires oxygen supply and the cooperation of pyruvate
      dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory
      chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into
      glucose. Congenital or acquired deficiency on gluconeogenesis or pyruvate
      oxidation, including tissue hypoxia, may induce lactate accumulation. Both obese
      individuals and patients with diabetes show elevated plasma lactate concentration
      compared to healthy subjects, but there is no conclusive evidence of
      hyperlactatemia causing insulin resistance. Available evidence suggests an
      association between defective mitochondrial oxidative capacity in the pancreatic
      beta-cells and diminished insulin secretion that may trigger the development of
      diabetes in patients already affected with insulin resistance. Several mutations
      in the mitochondrial DNA are associated with diabetes mellitus, although the
      pathogenesis remains unsettled. Mitochondrial DNA mutations have been detected in
      a number of human cancers. d-lactate is a lactate enantiomer normally formed
      during glycolysis. Excess d-lactate is generated in diabetes, particularly during
      diabetic ketoacidosis. d-lactic acidosis is typically associated with small bowel
      resection. 

PMID- 24929217
TI  - Toxic response of HIPCO single-walled carbon nanotubes in mice and RAW264.7
      macrophage cells.
AB  - In this study, we identified the toxic response of pristine single-walled carbon
      nanotubes (P-SWCNTs) synthesized by HIPCO method in mice and RAW264.7 cells, a
      murine peritoneal macrophage cell line. P-SWCNT contained a large amount of Fe
      ion (36 wt%). In the lungs of mice 24 h after intratracheal administration, P
      SWCNTs increased the secretion of IL-6 and MCP-1, and the number of total cells,
      the portion of neutrophils, lymphocytes, and eosinophils, also significantly
      increased at a 100 MUg/mL of concentration. In RAW264.7 cells, cell viability and
      ATP production decreased in a dose-dependent manner at 24 h after exposure,
      whereas the generations of ROS and NO were enhanced at all concentrations
      together with the activation of the MAP kinase pathway. Moreover, the levels of
      both apoptosis- and autophagy-related proteins and ER stress-related proteins
      clearly increased, and the concentrations of Fe, Cu, and Zn ions, but not of Mn
      ions, increased in a dose-dependent manner. TEM images also revealed that P
      SWCNTs induced the formation of autophagosome-like vacuoles, the dilatation of
      the ER, the generation of mitochondrial flocculent densities, and the separation
      of organelle by disappearance of the cell membrane. Taken together, we suggest
      that P-SWCNTs cause acute inflammatory response in the lungs of mice, and induce
      autophagy accompanied with apoptosis through mitochondrial dysfunction and ER
      stress in RAW264.7 cells. Furthermore, further study is required to elucidate how
      the physicochemical properties of SWCNTs determine the cell death pathway and an
      immune response.

PMID- 24929219
TI  - Exploiting genomic data to identify proteins involved in abalone reproduction.
AB  - Aside from their critical role in reproduction, abalone gonads serve as an
      indicator of sexual maturity and energy balance, two key considerations for
      effective abalone culture. Temperate abalone farmers face issues with tank
      restocking with highly marketable abalone owing to inefficient spawning induction
      methods. The identification of key proteins in sexually mature abalone will serve
      as the foundation for a greater understanding of reproductive biology. Addressing
      this knowledge gap is the first step towards improving abalone aquaculture
      methods. Proteomic profiling of female and male gonads of greenlip abalone,
      Haliotis laevigata, was undertaken using liquid chromatography-mass spectrometry.
      Owing to the incomplete nature of abalone protein databases, in addition to
      searching against two publicly available databases, a custom database comprising
      genomic data was used. Overall, 162 and 110 proteins were identified in females
      and males respectively with 40 proteins common to both sexes. For proteins
      involved in sexual maturation, sperm and egg structure, motility, acrosomal
      reaction and fertilization, 23 were identified only in females, 18 only in males
      and 6 were common. Gene ontology analysis revealed clear differences between the
      female and male protein profiles reflecting a higher rate of protein synthesis in
      the ovary and higher metabolic activity in the testis. BIOLOGICAL SIGNIFICANCE: A
      comprehensive mass spectrometry-based analysis was performed to profile the
      abalone gonad proteome providing the foundation for future studies of
      reproduction in abalone. Key proteins involved in both reproduction and energy
      balance were identified. Genomic resources were utilised to build a database of
      molluscan proteins yielding >60% more protein identifications than in a standard
      workflow employing public protein databases.

PMID- 24929220
TI  - Cognitive reappraisal of facial expressions: electrophysiological evidence of
      social anxiety.
AB  - The present study investigates the effect of cognitive reappraisal on emotion
      regulation in socially anxious individuals. Twenty-eight female subjects were
      divided into high-socially anxious (HSA) and low-socially anxious (LSA) groups.
      All subjects viewed threatening faces under cognitive reappraisal and passive
      viewing conditions, with subjective emotion ratings and event-related potentials
      (ERPs) recorded. Although the HSA and LSA groups reported similar amounts of
      reduction in emotion ratings while reappraising threatening faces, ERP data
      showed the LSA group generated a significantly larger stimuli-preceding
      negativity (SPN) than the HSA group when viewing the reappraisal cue word.
      Additionally, the LSA group, but not the HSA group, exhibited reduced P2-N2 peak
      to-peak values for the reappraisal condition relative to the passive viewing
      condition. These results suggest that the LSA subjects paid more attention to and
      prepared better for the upcoming emotion-regulating task than the HSA subjects.
      Unlike subjects in the HSA group, subjects in the LSA group could modulate face
      processing by reappraisal. In conclusion, cognitive reappraisal can be an
      effective emotion regulation strategy for socially anxious people, and a
      different neural mechanism may be involved for people who are not socially
      anxious. 

PMID- 24929218
TI  - Bayesian modeling of flexible cognitive control.
AB  - "Cognitive control" describes endogenous guidance of behavior in situations where
      routine stimulus-response associations are suboptimal for achieving a desired
      goal. The computational and neural mechanisms underlying this capacity remain
      poorly understood. We examine recent advances stemming from the application of a
      Bayesian learner perspective that provides optimal prediction for control
      processes. In reviewing the application of Bayesian models to cognitive control,
      we note that an important limitation in current models is a lack of a plausible
      mechanism for the flexible adjustment of control over conflict levels changing at
      varying temporal scales. We then show that flexible cognitive control can be
      achieved by a Bayesian model with a volatility-driven learning mechanism that
      modulates dynamically the relative dependence on recent and remote experiences in
      its prediction of future control demand. We conclude that the emergent Bayesian
      perspective on computational mechanisms of cognitive control holds considerable
      promise, especially if future studies can identify neural substrates of the
      variables encoded by these models, and determine the nature (Bayesian or
      otherwise) of their neural implementation.

PMID- 24929221
TI  - LOX-1 and neurodegeneration.

PMID- 24929222
TI  - Multidrug resistance in cancer or inefficacy of neuroactive agents: innovative
      strategies to inhibit or circumvent the active efflux transporters selectively.
AB  - Multidrug resistance (MDR) is a crucial issue in the treatment of cancer cells
      that protect themselves by overexpression of active efflux transporters (AETs).
      AET expression maintains the homeostasis in healthy tissues and in the blood
      brain barrier it often prevents drugs from reaching the brain. Inhibition of AETs
      could therefore be a valuable solution for preventing MDR; but nonselective long
      term AET blocking can be harmful toward healthy tissues and, in particular, the
      brain. This review looks at the development of innovative formulations suitable
      for selectively blocking or avoiding AETs as promising ways to overcome the
      challenges of MDR and inefficacy of neuroactive agents. 

PMID- 24929223
TI  - Pharmacokinetics, metabolism and distribution of PEGs and PEGylated proteins: quo
      vadis?
AB  - The pharmacokinetics (PK), metabolism and biodistribution of polyethylene glycol
      (PEG) in PEGylated proteins are important to understand the increased cellular
      vacuolation reported in various tissues in animals. The tissue distribution
      profile of PEGylated proteins and 'metabolic' PEG is guided largely by absolute
      PEG load, PEG molecular weight and, where applicable, receptor-mediated uptake
      via the protein moiety. High molecular weight PEGs show slow renal clearance, and
      consequently have a greater potential to accumulate within cells. The
      intracellular nonbiodegradable PEG can accumulate within the lysosome ultimately
      causing distension and vacuolation observed by standard histological
      examinations. Improved bioanalytical methodologies will contribute to the
      identification of specific PK parameters including distribution behavior to
      support development of PEGylated proteins as therapeutics. 

PMID- 24929224
TI  - Gene-environment interplay in Drosophila melanogaster: chronic nutritional
      deprivation in larval life affects adult fecal output.
AB  - Life history consequences of stress in early life are varied and known to have
      lasting impacts on the fitness of an organism. Gene-environment interactions play
      a large role in how phenotypic differences are mediated by stressful conditions
      during development. Here we use natural allelic 'rover/sitter' variants of the
      foraging (for) gene and chronic early life nutrient deprivation to investigate
      gene-environment interactions on excretion phenotypes. Excretion assay analysis
      and a fully factorial nutritional regimen encompassing the larval and adult life
      cycle of Drosophila melanogaster were used to assess the effects of larval and
      adult nutritional stress on adult excretion phenotypes. Natural allelic variants
      of for exhibited differences in the number of fecal spots when they were
      nutritionally deprived as larvae and well fed as adults. for mediates the
      excretion response to chronic early-life nutritional stress in mated female,
      virgin female, and male rovers and sitters. Transgenic manipulations of for in a
      sitter genetic background under larval but not adult food deprivation increases
      the number of fecal spots. Our study shows that food deprivation early in life
      affects adult excretion phenotypes and these excretion differences are mediated
      by for. 

PMID- 24929226
TI  - A spatial model with pulsed releases to compare strategies for the sterile insect
      technique applied to the mosquito Aedes aegypti.
AB  - We present a simple mathematical model to replicate the key features of the
      sterile insect technique (SIT) for controlling pest species, with particular
      reference to the mosquito Aedes aegypti, the main vector of dengue fever. The
      model differs from the majority of those studied previously in that it is
      simultaneously spatially explicit and involves pulsed, rather than continuous,
      sterile insect releases. The spatially uniform equilibria of the model are
      identified and analysed. Simulations are performed to analyse the impact of
      varying the number of release sites, the interval between pulsed releases and the
      overall volume of sterile insect releases on the effectiveness of SIT programmes.
      Results show that, given a fixed volume of available sterile insects, increasing
      the number of release sites and the frequency of releases increases the
      effectiveness of SIT programmes. It is also observed that programmes may become
      completely ineffective if the interval between pulsed releases is greater that a
      certain threshold value and that, beyond a certain point, increasing the overall
      volume of sterile insects released does not improve the effectiveness of SIT. It
      is also noted that insect dispersal drives a rapid recolonisation of areas in
      which the species has been eradicated and we argue that understanding the density
      dependent mortality of released insects is necessary to develop efficient, cost
      effective SIT programmes. 

PMID- 24929225
TI  - Both children and adults scan faces of own and other races differently.
AB  - Extensive behavioral and neural evidence suggests that processing of own-race
      faces differs from that of other-race faces in both adults and infants. However,
      little research has examined whether and how children scan faces of own and other
      races differently for face recognition. In this eye-tracking study, Chinese
      children aged from 4 to 7 years and Chinese adults were asked to remember Chinese
      and Caucasian faces. None of the participants had any direct contact with foreign
      individuals. Multi-method analyses of eye-tracking data revealed that regardless
      of age group, proportional fixation duration on the eyes of Chinese faces was
      significantly lower than that on the eyes of Caucasian faces, whereas
      proportional fixation duration on the nose and mouth of Chinese faces was
      significantly higher than that on the nose and mouth of Caucasian faces. In
      addition, the amplitude of saccades on Chinese faces was significantly lower than
      that on Caucasian faces, potentially reflecting finer-grained processing for own
      race faces. Moreover, adults' fixation duration/saccade numbers on the whole
      faces, proportional fixation percentage on the nose, proportional number of
      saccades between AOIs, and accuracy in recognizing faces were higher than those
      of children. These results together demonstrate that an abundance of visual
      experience with own-race faces and a lack of it with other-race faces may result
      in differential facial scanning in both children and adults. Furthermore, the
      increased experience of processing faces may result in a more holistic and
      advanced scanning strategy in Chinese adults.

PMID- 24929227
TI  - Extensive review of fish embryo acute toxicities for the prediction of GHS acute
      systemic toxicity categories.
AB  - Distribution and marketing of chemicals require appropriate labelling of health,
      physical and environmental hazards according to the United Nations global
      harmonisation system (GHS). Labelling for (human) acute toxicity categories is
      based on experimental findings usually obtained by oral, dermal or inhalative
      exposure of rodents. There is a strong societal demand for replacing animal
      experiments conducted for safety assessment of chemicals. Fish embryos are
      considered as alternative to animal testing and are proposed as predictive model
      both for environmental and human health effects. Therefore, we tested whether
      LC50s of the fish embryo acute toxicity test would allow effectively predicting
      of acute mammalian toxicity categories. A database of published fish embryo LC50
      containing 641 compounds was established. For these compounds corresponding rat
      oral LD50 were identified resulting in 364 compounds for which both fish embryo
      LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and
      rat oral LD50 was obtained. Fish embryos were also not able to effectively
      predict GHS oral acute toxicity categories. We concluded that due to fundamental
      exposure protocol differences (single oral dose versus water-borne exposure) a
      reverse dosimetry approach is needed to explore the predictive capacity of fish
      embryos.

PMID- 24929228
TI  - An insulin-like androgenic gland hormone gene in the mud crab, Scylla
      paramamosain, extensively expressed and involved in the processes of growth and
      female reproduction.
AB  - Insulin-like androgenic gland hormone (IAG) produced by androgenic gland (AG) in
      male crustaceans is regarded as a key regulator of sex differentiation. As a
      member of the insulin/insulin-like growth factor family, IAG is also likely
      involved in regulating somatic growth. In this study, a full-length cDNA of IAG
      (termed Sp-IAG) was isolated from the mud crab, Scylla paramamosain. Genomic DNA
      of Sp-IAG was also cloned, analysis of which reveals that Sp-IAG gene is
      organized in a 4 exon/3 intron manner. RNA in situ hybridization analysis
      detected positive signals in both type I and type II AG cells. Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis showed that Sp-IAG was
      expressed not only in AG, but also in many other tissues. Sp-IAG expression
      levels in ovaries were examined at different stages of ovarian development
      (stages I to V); it was found that the expression was maintained at low levels
      during undeveloped stage (stage I) to late vitellogenic stage (stage IV) and then
      increased significantly at mature stage (stage V), suggesting that Sp-IAG may
      participate in inhibiting oocyte growth and vitellogenesis. The expression
      pattern of Sp-IAG during the molting cycle of the first stage crabs (C1) was also
      determined. Sp-IAG expression level continuously decreased from 0 h C1 (postmolt)
      crabs to 96 h C1 (premolt) crabs, and then increased significantly in the newly
      molted second stage crabs (C2, postmolt). The combined results suggested for the
      first time that IAG is involved in regulating ovarian development and somatic
      growth in crustaceans.

PMID- 24929229
TI  - Avian photoreceptors and their role in the regulation of daily and seasonal
      physiology.
AB  - Birds time their activities in synchronization with daily and seasonal
      periodicities in the environment, which is mainly provided by changes in day
      length (=photoperiod). Photoperiod appears to act at different levels than simply
      entraining the hypothalamic clock via eyes in birds. Photoreceptor cells that
      transmit light information to an avian brain are localized in three independent
      structures, the retina of eyes, pineal gland and hypothalamus, particularly in
      the paraventricular organ and lateral septal area. These hypothalamic
      photoreceptors are commonly referred to as encephalic or deep brain
      photoreceptors, DBPs. Eyes and pineal are known to contribute to the circadian
      regulation of behavior and physiology via rhythmic melatonin secretion in several
      birds. DBPs have been implicated in the regulation of seasonal physiology,
      particularly in photoperiod induced gonadal growth and development. Here, we
      briefly review limited evidence that is available on the roles of these
      photoreceptors in the regulation of circadian and seasonal physiology, with
      particular emphasis placed on the DBPs. 

PMID- 24929230
TI  - Involvement of Galphas-proteins in the action of relaxin-like gonad-stimulating
      substance on starfish ovarian follicle cells.
AB  - Gonad-stimulating substance (GSS) in starfish is the only known invertebrate
      peptide hormone responsible for final gamete maturation, rendering it
      functionally analogous to gonadotropins in vertebrates. In breeding season (stage
      V), GSS stimulates oocyte maturation to induce 1-methyladenine (1-MeAde) by
      ovarian follicle cells. The hormonal action of GSS is mediated through the
      activation of its receptor, G-proteins and adenylyl cyclase. It has been reported
      that GSS fails to induce 1-MeAde and cyclic AMP (cAMP) production in follicle
      cells of ovaries during oogenesis (stage IV). This study examined the regulatory
      mechanism how ovarian follicle cells acquire the potential to respond to GSS by
      producing 1-MeAde and cAMP. Because the failure of GSS action was due to G
      proteins of follicle cells, the molecular structures of Galphas, Galphai, Galphaq
      and Gbeta were identified in follicle cells of starfish Asterina pectinifera. The
      cDNA sequences of Galphas, Galphai, Galphaq and Gbeta consisted of ORFs encoding
      379, 354, 353 and 353 amino acids. The expression levels of Galphas were
      extremely low in follicle cells at stage IV, whereas the mRNA levels increased
      markedly in stage V. On contrary, the mRNA levels of Galphai were almost constant
      regardless of stage IV and V. These findings strongly suggest that de novo
      synthesis of Galphas-proteins is contributed to the action of GSS on follicle
      cells to produce 1-MeAde and cAMP. 

PMID- 24929231
TI  - Anorexigenic effects of central adrenomedullin are associated with hypothalamic
      changes in juvenile Gallus gallus.
AB  - Adrenomedullin (AM), a 52 residue neuropeptide, is associated with anorexia in
      mammals and has a poorly understood central mechanism of action. Thus, this study
      focused on elucidating AM's central mechanism of action in an alternative
      vertebrate model, the chick (Gallus gallus). In Experiment 1, chicks centrally
      injected with AM dose-dependently reduced food but not water intake. In
      Experiment 2, those chicks that received central AM had increased c-Fos
      immunoreactivity in the magnocellular division of the paraventricular nucleus
      (PaMC), ventromedial hypothalamus (VMH) and doromedial hypothalamus (DM). The
      lateral hypothalamic area, parvocellular division of the paraventricular
      hypothalamus and the arcuate nucleus were not affected. In Experiment 3,
      antagonism of corticotrophin releasing factor (CRF) receptors did not affect AM
      associated anorexia. In Experiment 4, a comprehensive behavior analysis was
      conducted and AM-treated chicks pecked less, moved more, jumped more and spent
      more time in deep rest. In conclusion, exogenous AM induced anorexia is
      associated with activation of the PaMC, VMH and DM of the hypothalamus, is not
      CRF dependent, and affects behaviors unrelated to food intake in chicks. 

PMID- 24929232
TI  - Seasonal variation in glucocorticoid and mineralocorticoid receptors in metabolic
      tissues of the house sparrow (Passer domesticus).
AB  - Glucocorticoid hormones like corticosterone (CORT) play essential metabolic roles
      at both baseline and stress-induced concentrations, and CORT titers vary
      seasonally in patterns occurring across many different vertebrate species. It has
      been hypothesized that CORT may vary seasonally due to changing energy
      requirements at different times of year. However, hormone effects are dependent
      on binding to receptors in target tissues, and receptors might also vary
      seasonally. CORT alters metabolism primarily through binding to two receptors,
      the high-affinity mineralocorticoid receptor (MR) and low-affinity glucocorticoid
      receptor (GR). We quantified GR and MR in metabolic tissues (liver, kidney,
      omental and subcutaneous fat, and gastrocnemius and pectoralis muscle) of wild
      caught house sparrows (Passer domesticus) to assess these tissues' capacity to
      respond to CORT-mediated metabolic demands. We quantified receptors using
      radioligand binding assays in early and late winter, pre-egg-laying, breeding,
      late breeding and molt (n=12 at each stage). MR binding did not vary
      significantly in any tissue over the course of the year. Because MR is associated
      with baseline CORT effects, this suggests that changing hormone titers may
      primarily regulate baseline CORT effects on metabolism. Seasonal modulation of GR
      binding occurred in every tissue but omental fat, though peak receptor density
      did not coincide with peak stress-induced CORT concentrations measured
      previously. Because GR is associated with stress-induced CORT effects, these data
      demonstrate seasonal patterns in stress-induced CORT are not driven by metabolic
      needs alone, although at different times of year sparrows may vary which tissue
      types respond to increased energy demands resulting from exposure to stressors. 

PMID- 24929233
TI  - Molecular and morphological changes in zebrafish following transient ethanol
      exposure during defined developmental stages.
AB  - Alcohol is a teratogen that has diverse effects on brain and craniofacial
      development, leading to a constellation of developmental disorders referred to as
      fetal alcohol spectrum disorder (FASD). The molecular basis of ethanol insult
      remains poorly understood, as does the relationship between molecular and
      behavioral changes as a consequence of prenatal ethanol exposure. Zebrafish
      embryos were exposed to a range of ethanol concentrations (0.5-5.0%) during
      defined developmental stages, and examined for morphological phenotypes
      characteristic of FASD. Embryos were also analyzed by in situ hybridization for
      changes in expression of defined cell markers for neural cell types that are
      sonic hedgehog-dependent. We show that transient binge-like ethanol exposures
      during defined developmental stages, such as early gastrulation and early
      neurulation, result in a range of phenotypes and changes in expression of Shh
      dependent genes. The severity of fetal alcohol syndrome (FAS) morphological
      phenotypes, such as microphthalmia, depends on the embryonic stage and
      concentration of alcohol exposure, as does diminution of retinal Pax6a or
      forebrain and hindbrain GAD1 gene expression. We also show that changes in eye
      and brain morphology correlate with changes in Pax6a and GAD1 gene expression.
      Our results therefore show that transient binge-like ethanol exposures in
      zebrafish embryos produce the stereotypical morphological phenotypes of FAS, with
      the severity of phenotypes depending on the developmental stage and alcohol
      concentration of exposure. 

PMID- 24929234
TI  - Neuropharmacological and cochleotoxic effects of styrene. Consequences on noise
      exposures.
AB  - Occupational noise exposure can damage workers' hearing, particularly when
      combined with exposure to cochleotoxic chemicals such as styrene. Although
      styrene-induced cochlear impairments only become apparent after a long incubation
      period, the pharmacological impact of styrene on the central nervous system (CNS)
      can be rapidly measured by determining the threshold of the middle-ear acoustic
      reflex (MER) trigger. The aim of the study was to evaluate the effects of a noise
      (both continuous and impulse), and a low concentration of styrene
      [300ppm<(threshold limit value*10) safety factor] on the peripheral auditory
      receptor, and on the CNS in rats. The impact of the different conditions on
      hearing loss was assessed using distortion product oto-acoustic emissions, and
      histological analysis of cochleae. Although the LEX,8h (8-hour time-weighted
      average exposure) of the impulse noise was lower (80dB SPL sound pressure level)
      than that of the continuous noise (85dB SPL), it appeared more detrimental to the
      peripheral auditory receptors. A co-exposure to styrene and continuous noise was
      less damaging than exposure to continuous noise alone. In contrast, the traumatic
      effects of impulse noise on the organ of Corti were enhanced by co-exposure to
      styrene. The pharmacological effects of the solvent on the CNS were discussed to
      put forward a plausible explanation of these surprising results. We hypothesize
      that CNS effects of styrene may account for this apparent paradox. Based on the
      present results, the temporal structure of the noise should be reintroduced as a
      key parameter in hearing conservation regulations. 

PMID- 24929236
TI  - Lymphangioma of the colon: a curious endoscopic finding.

PMID- 24929235
TI  - No resistance to tenofovir disoproxil fumarate through 96 weeks of treatment in
      patients with lamivudine-resistant chronic hepatitis B.
AB  - BACKGROUND & AIMS: A recent study compared the efficacy of tenofovir disoproxil
      fumarate (TDF) vs the combination of emtricitabine and TDF (FTC/TDF) in patients
      with lamivudine-resistant chronic hepatitis B who were treated for as long as 96
      weeks. We report findings from resistance analyses conducted for this study.
      METHODS: Two hundred eighty patients with chronic hepatitis B virus (HBV)
      infection and lamivudine resistance (confirmed by INNO-LiPA Multi-DR) were
      randomly assigned (1:1) to groups treated with TDF or FTC/TDF. The HBV reverse
      transcriptase domain from the polymerase gene from all patients was sequenced at
      baseline and from 18 viremic patients at week 96 or early discontinuation.
      RESULTS: At screening for the efficacy study, 99% of patients were found to have
      lamivudine resistance. Prior exposure to entecavir or entecavir resistance was
      observed in 12% of patients, and 22% of patients had been previously exposed to
      adefovir; 1.8% were resistant to adefovir. Only 18 patients (6.4%) qualified for
      sequence analysis, including 1 patient who experienced virologic breakthrough and
      17 with persistent viremia. Six of these patients did not have any sequence
      changes from baseline in HBV reverse transcriptase (33%), and sequence analysis
      could not be performed for 5 patients (28%). In 2 patients who qualified for
      phenotypic analysis (1 given TDF and 1 given FTC/TDF), no resistance to TDF was
      observed. Neither previous treatment exposure nor resistance to entecavir or
      adefovir affected viral kinetics. However, the mean baseline level of HBV DNA was
      significantly higher in viremic patients than in patients with viral suppression
      by week 96 (7.28 log10 IU/mL vs 5.62 log10 IU/mL; P = .0003). CONCLUSIONS: No
      resistance to TDF was detected through 96 weeks of treatment in patients with
      lamivudine-resistant chronic hepatitis B. Prior treatment or resistance to
      entecavir or adefovir did not affect viral kinetics through 96 weeks. No
      additional benefit was observed with the addition of emtricitabine vs TDF
      monotherapy. ClinicalTrial.gov number: NCT00737568.

PMID- 24929238
TI  - Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in
      developing mouse epiblast.
AB  - Nanog, a core pluripotency factor, is required for stabilizing pluripotency of
      inner cell mass (ICM) and embryonic stem cells (ESCs), and survival of primordial
      germ cells in mice. Here, we have addressed function and regulation of Nanog in
      epiblasts of postimplantation mouse embryos by conditional knockdown (KD),
      chromatin immunoprecipitation (ChIP) using in vivo epiblasts, and protein
      interaction with the Nanog promoter in vitro. Differentiation of Nanog-KD
      epiblasts demonstrated requirement for Nanog in stabilization of pluripotency.
      Nanog expression in epiblast is directly regulated by Nodal/Smad2 pathway in a
      visceral endoderm-dependent manner. Notably, Nanog promoters switch from
      Oct4/Esrrb in ICM/ESCs to Oct4/Smad2 in epiblasts. Smad2 directly associates with
      Oct4 to form Nanog promoting protein complex. Collectively, these data
      demonstrate that Nanog plays a key role in stabilizing Epiblast pluripotency
      mediated by Nodal/Smad2 signaling, which is involved in Nanog promoter switching
      in early developing embryos. 

PMID- 24929237
TI  - SLC6 family transporter SNF-10 is required for protease-mediated activation of
      sperm motility in C. elegans.
AB  - Motility of sperm is crucial for their directed migration to the egg. The
      acquisition and modulation of motility are regulated to ensure that sperm move
      when and where needed, thereby promoting reproductive success. One specific
      example of this phenomenon occurs during differentiation of the ameboid sperm of
      Caenorhabditis elegans as they activate from a round spermatid to a mature,
      crawling spermatozoon. Sperm activation is regulated by redundant pathways to
      occur at a specific time and place for each sex. Here, we report the
      identification of the solute carrier 6 (SLC6) transporter protein SNF-10 as a key
      regulator of C. elegans sperm activation in response to male protease activation
      signals. We find that SNF-10 is present in sperm and is required for activation
      by the male but not by the hermaphrodite. Loss of both snf-10 and a hermaphrodite
      activation factor render sperm completely insensitive to activation. Using in
      vitro assays, we find that snf-10 mutant sperm show a specific deficit in
      response to protease treatment but not to other activators. Prior to activation,
      SNF-10 is present in the plasma membrane, where it represents a strong candidate
      to receive signals that lead to subcellular morphogenesis. After activation, it
      shows polarized localization to the cell body region that is dependent on
      membrane fusions mediated by the dysferlin FER-1. Our discovery of snf-10 offers
      insight into the mechanisms differentially employed by the two sexes to
      accomplish the common goal of producing functional sperm, as well as how the
      physiology of nematode sperm may be regulated to control motility as it is in
      mammals. 

PMID- 24929239
TI  - Unopposed cathepsin G, neutrophil elastase, and proteinase 3 cause severe lung
      damage and emphysema.
AB  - Cigarette smoking is a major factor for the development of pulmonary emphysema
      because it induces abnormal inflammation and a protease-rich local milieu that
      causes connective tissue breakdown of the lungs. As a result of its capacity to
      degrade lung tissue and the high risk of patients lacking alpha1-antitrypsin to
      develop emphysema, much interest has focused on neutrophil elastase (NE). Two
      similar neutrophil serine proteases (NSPs), cathepsin G and proteinase 3, coexist
      with NE in humans and mice, but their potential tissue-destructive role(s)
      remains unclear. Using a gene-targeting approach, we observed that in contrast to
      their wild-type littermates, mice deficient in all three NSPs were substantially
      protected against lung tissue destruction after long-term exposure to cigarette
      smoke. In exploring the underlying basis for disrupted wild-type lung air spaces,
      we found that active NSPs collectively caused more severe lung damage than did NE
      alone. Furthermore, NSP activities unleashed increased activity of the tissue
      destructive proteases macrophage elastase (matrix metalloproteinase-12) and
      gelatinase B (matrix metalloproteinase-9). These in vivo data provide, for the
      first time, compelling evidence of the collateral involvement of cathepsin G, NE,
      and proteinase 3 in cigarette smoke-induced tissue damage and emphysema. They
      also reveal a complex positive feed-forward loop whereby these NSPs induce the
      destructive potential of other proteases, thereby generating a chronic and
      pathogenic protease-rich milieu. 

PMID- 24929240
TI  - Combinatorial therapy with acetylation and methylation modifiers attenuates lung
      vascular hyperpermeability in endotoxemia-induced mouse inflammatory lung injury.
AB  - Impairment of tissue fluid homeostasis and migration of inflammatory cells across
      the vascular endothelial barrier are crucial factors in the pathogenesis of acute
      lung injury (ALI). The goal for treatment of ALI is to target pathways that lead
      to profound dysregulation of the lung endothelial barrier. Although studies have
      shown that chemical epigenetic modifiers can limit lung inflammation in
      experimental ALI models, studies to date have not examined efficacy of a
      combination of DNA methyl transferase inhibitor 5-Aza 2-deoxycytidine and histone
      deacetylase inhibitor trichostatin A (herein referred to as Aza+TSA) after
      endotoxemia-induced mouse lung injury. We tested the hypothesis that treatment
      with Aza+TSA after lipopolysaccharide induction of ALI through epigenetic
      modification of lung endothelial cells prevents inflammatory lung injury.
      Combinatorial treatment with Aza+TSA mitigated the increased endothelial
      permeability response after lipopolysaccharide challenge. In addition, we
      observed reduced lung inflammation and lung injury. Aza+TSA also significantly
      reduced mortality in the ALI model. The protection was ascribed to inhibition of
      the eNOS-Cav1-MLC2 signaling pathway and enhanced acetylation of histone markers
      on the vascular endothelial-cadherin promoter. In summary, these data show for
      the first time the efficacy of combinatorial Aza+TSA therapy in preventing ALI in
      lipopolysaccharide-induced endotoxemia and raise the possibility of an essential
      role of DNA methyl transferase and histone deacetylase in the mechanism of ALI. 

PMID- 24929241
TI  - Moderate intensity resistive exercise improves metaphyseal cancellous bone
      recovery following an initial disuse period, but does not mitigate decrements
      during a subsequent disuse period in adult rats.
AB  - Spaceflight provides a unique environment for skeletal tissue causing decrements
      in structural and densitometric properties of bone. Previously, we used the adult
      hindlimb unloaded (HU) rat model to show that previous exposure to HU had minimal
      effects on bone structure after a second HU exposure followed by recovery.
      Furthermore, we found that the decrements during second HU exposure were milder
      than the initial HU cycle. In this study, we used a moderate intensity resistance
      exercise protocol as an anabolic stimulus during recovery to test the hypothesis
      that resistance exercise following an exposure to HU will significantly enhance
      recovery of densitometric, structural, and, more importantly, mechanical
      properties of trabecular and cortical bone. We also hypothesized that resistance
      exercise during recovery, and prior to the second unloading period, will mitigate
      the losses during the second exposure. The hypothesis that exercise during
      recovery following hindlimb unloading will improve bone quality was supported by
      our data, as total BMC, total vBMD, and cancellous bone formation at the proximal
      tibia metaphysis increased significantly during exercise period, and total
      BMC/vBMD exceeded age-matched control and non-exercised values significantly by
      the end of recovery. However, our results did not support the hypothesis that
      resistance exercise prior to a subsequent unloading period will mitigate the
      detrimental effects of the second exposure, as the losses during the second
      exposure in total BMC, total vBMD, and cortical area at the proximal tibia
      metaphysis for the exercised animals were similar to those of the non-exercised
      group. Therefore, exercise did not mitigate effects of the second HU exposure in
      terms of pre-to-post HU changes in these variables, but it did produce beneficial
      effects in a broader sense. 

PMID- 24929242
TI  - Msx1 role in craniofacial bone morphogenesis.
AB  - The homeobox gene Msx1 encodes a transcription factor that is highly expressed
      during embryogenesis and postnatal development in bone. Mutations of the MSX1
      gene in humans are associated with cleft palate and (or) tooth agenesis. A
      similar phenotype is observed in newborn mice invalidated for the Msx1 gene.
      However, little is known about Msx1 function in osteoblast differentiation and
      bone mineralization in vivo. In the present study, we aimed to explore the
      variations of individualized bone shape in a subtle way avoiding the often severe
      consequences associated with gene mutations. We established transgenic mice that
      specifically express Msx1 in mineral-matrix-secreting cells under the control of
      the mouse 2.3kb collagen 1 alpha 1 (Col1alpha1) promoter, which enabled us to
      investigate Msx1 function in bone in vivo. Adult transgenic mice (Msx1-Tg)
      presented altered skull shape and mineralization resulting from increased Msx1
      expression during bone development. Serial section analysis of the mandibles
      showed a high amount of bone matrix in these mice. In addition, osteoblast
      number, cell proliferation and apoptosis were higher in Msx1-Tg mice than in
      controls with regional differences that could account for alterations of bone
      shape. However, Von Kossa staining and MUCT analysis showed that bone
      mineralization was lower in Msx1-Tg mice than in controls due to alteration of
      osteoblastic differentiation. Msx1 appears to act as a modeling factor for
      membranous bone; it stimulates trabecular bone metabolism but limits cortical
      bone growth by promoting apoptosis, and concomitantly controls the collagen-based
      mineralization process. 

PMID- 24929243
TI  - Characterization of a lectin from the craysfish Cherax quadricarinatus hemolymph
      and its effect on hemocytes.
AB  - Lectins participate in the immune mechanisms of crustaceans. They have been
      considered as humoral receptors for pathogen-associated molecular patterns;
      however, some reports suggest that lectins could regulate crustacean cellular
      functions. In the present study, we purified and characterized a serum lectin
      (CqL) from the hemolymph of Cherax quadricarinatus by affinity chromatography and
      determined its participation in the regulation of hemocytes' oxidative burst. CqL
      is a 290-kDa lectin in native form, constituted by 108, 80, and 29-kDa subunits.
      It is mainly composed of glycine, alanine, and a minor proportion of methionine
      and histidine. It showed no carbohydrates in its structure. CqL is composed of
      several isoforms, as determined by 2D-electrophoresis, and shows no homology with
      any crustacean protein as determined by Lc/Ms mass spectrometry. CqL agglutinated
      mainly rat and rabbit erythrocytes and showed a broad specificity for
      monosaccharides such as galactose, glucose, and sialic acid, as well as for
      glycoproteins, such as porcine stomach and bovine submaxillary mucin and fetuin.
      It is a Mn(2+)-dependent lectin. CqL recognized 8% of crayfish granular hemocytes
      and increased 4.2-fold the production of hemocytes' superoxide anion in vitro
      assays when compared with non-treated hemocytes. This effect showed the same
      specificity for carbohydrates as hemagglutination; moreover, superoxide dismutase
      and diphenyleneiodonium chloride were effective inhibitors of CqL oxidative
      activation. The CqL homoreceptor is a 120-kDa glycoprotein identified in the
      hemocytes lysate. Our results suggest that CqL participates actively in the
      regulation of the generation of superoxide anions in hemocytes using NADPH
      dependent mechanisms.

PMID- 24929244
TI  - Classification and phagocytosis of circulating haemocytes in Chinese mitten crab
      (Eriocheir sinensis) and the effect of extrinsic stimulation on circulating
      haemocytes in vivo.
AB  - Eriocheir sinensis (Henri Milne Edwards 1854) is one of the most important
      aquaculture species in China. In this investigation, we characterised the
      different types of haemocytes of E. sinensis using light and electron microscopy
      combined with cytochemical analysis and determined the in vivo phagocytic ability
      of different haemocyte types by injecting polystyrene beads. The haemocytes of E.
      sinensis were divided into three types: hyalinocytes, semigranulocytes and
      granulocytes. The hyalinocytes had no or few cytoplasmic granules; the
      semigranulocytes contained abundant small granules and a few large refractile
      cytoplasmic granules; and the granulocytes contained numerous large refractile
      cytoplasmic granules. The hyalinocytes were demonstrated to be the most abundant
      circulating haemocytes and the most avid phagocytic haemocytes, accounting for
      approximately 88.7% of the total phagocytes. The haemocyte-containing granules
      displayed limited phagocytic ability, with approximately 5.0% of granulocytes and
      6.3% of semigranulocytes displaying positive phagocytic ability against the
      invading polystyrene beads in vivo. After injection with Aeromonas hydrophila,
      Bacillus subtilis and different concentrations of lipopolysaccharide for 0.25,
      0.5, 1, 2, 4, 6 and 8 h, all three types of haemocytes experienced dramatic
      decline and then rapid recovery to their initial levels. A high concentration of
      lipopolysaccharide and A. hydrophila were extremely toxic to the crabs, as they
      induced a more serious loss of haemocytes compared with a low concentration of
      lipopolysaccharide and B. subtilis. Overall, the results obtained in this study
      indicate that a small proportion of the haemocytes of E. sinensis contributed to
      the phagocytic process, and the migration of haemocytes and haemocyte lysis were
      most likely a prominent pathway for pathogen elimination.

PMID- 24929245
TI  - Incongruence among different mitochondrial regions: a case study using complete
      mitogenomes.
AB  - Mitochondrial sequences have long been used to examine vertebrate phylogenetic
      relationships. The extensive use of mitochondrial data reflects the ease of
      obtaining mitochondrial sequences and its relatively rapid coalescence time.
      Mitochondrial genomes typically do not undergo recombination, so the entire
      mitogenome should have the same underlying gene tree. Thus, given appropriate
      analyses, conflict among estimates of phylogeny from different mitochondrial
      regions should not exist. However, estimates of phylogeny based upon different
      mitochondrial regions can exhibit incongruence. Conflict in phylogenetic signal
      among mitochondrial regions has been observed in galliform birds for the position
      of the Odontophoridae (New World quail). To explore this, we expanded sampling to
      47 galliform mitogenomes, adding six new mitogenomes, which included
      representatives of two previously unsampled families. Analyses of complete
      mitogenomes recovered a well-supported topology that was congruent with
      expectations from multi-locus studies. However, when analyzing individual
      regions, we found conflicting positions for the Odontophoridae and several other
      relationships at multiple taxonomic levels. We tested multiple analytical
      strategies to reduce incongruence among regions, including partitioning by codon
      position, using mixture and codon-based models, RY coding, and excluding
      potentially misleading sites. No approach consistently reduced the conflict among
      mitochondrial regions at any taxonomic level. The biological attributes of both
      strongly misleading and non-misleading sites were essentially identical.
      Increasing taxa actually appeared to increase conflicting signal, even when taxa
      were selected to break up long branches. Collectively, our results indicate that
      analyzing mitochondrial data remains difficult, although analyzing complete
      mitogenomes resulted in a good estimate of the mitochondrial gene tree. 

PMID- 24929246
TI  - Dubious resolution and support from published sparse supermatrices: the
      importance of thorough tree searches.
AB  - We re-analyzed 10 sparse supermatrices wherein the original authors relied
      primarily or entirely upon maximum likelihood phylogenetic analyses implemented
      in RAxML and quantified branch support using the bootstrap. We compared the RAxML
      based topologies and bootstrap values with both superficial- and relatively
      thorough-tree-search parsimony topologies and bootstrap values. We tested for
      clades that were resolved by RAxML but properly unsupported by checking if the SH
      like aLRT equals zero and/or if the parsimony-optimized minimum branch length
      equals zero. Four of our conclusions are as follows. (1) Despite sampling nearly
      50,000 characters, highly supported branches in a RAxML tree may be entirely
      unsupported because of missing data. (2) One should not rely entirely upon RAxML
      SH-like aLRT, RAxML bootstrap, or superficial parsimony bootstrap methods to
      rigorously quantify branch support for sparse supermatrices. (3) A fundamental
      factor that favors thorough parsimony analyses of sparse supermatrices is being
      able to distinguish between clades that are unequivocally supported by the data
      from those that are not; superficial likelihood analyses that quantify branch
      support using the bootstrap cannot be relied upon to always make this
      distinction. (4) The SH-like aLRT and parsimony-optimized-minimum-branch-length
      tests generally identify the same properly unsupported clades; the latter is a
      more severe test. 

PMID- 24929247
TI  - Molecular systematics and biogeography of Logania R.Br. (Loganiaceae).
AB  - The angiosperm genus Logania R.Br. (Loganiaceae) is endemic to the mainland of
      Australia. A recent genetic study challenged the monophyly of Logania, suggesting
      that its two sections, Logania sect. Logania and Logania sect. Stomandra, do not
      group together. Additionally, the genus has a disjunct distribution, with a gap
      at the Nullarbor Plain in southern Australia. Therefore, Logania is a favourable
      candidate to gain insight into phylogenetic relationships and how these might
      intersect with Earth-history events. Our phylogenetic analyses of DNA sequences
      of two chloroplast markers (petD and rps16) showed that Logania sect. Logania and
      L. sect. Stomandra were each resolved as monophyletic, but the genus (as
      currently circumscribed) was not. Based on our Bayesian estimates of divergence
      times, the disjunct distributions within Logania sect. Stomandra could have been
      caused by flooding of the Eucla Basin. However, this biogeographical process
      cannot account for the distribution of Logania sect. Logania, with long-distance
      dispersal and establishment seeming more likely. 

PMID- 24929248
TI  - Limit of blank and limit of detection of Plasmodium falciparum thick blood smear
      microscopy in a routine setting in Central Africa.
AB  - BACKGROUND: Proper malaria diagnosis depends on the detection of asexual forms of
      Plasmodium spp. in the blood. Thick blood smear microscopy is the accepted gold
      standard of malaria diagnosis and is widely implemented. Surprisingly, diagnostic
      performance of this method is not well investigated and many clinicians in
      African routine settings base treatment decisions independent of microscopy
      results. This leads to overtreatment and poor management of other febrile
      diseases. Implementation of quality control programmes is recommended, but
      requires sustained funding, external logistic support and constant training and
      supervision of the staff. This study describes an easily applicable method to
      assess the performance of thick blood smear microscopy by determining the limit
      of blank and limit of detection. These two values are representative of the
      diagnostic quality and allow the correct discrimination between positive and
      negative samples. METHODS: Standard-conform methodology was applied and adapted
      to determine the limit of blank and the limit of detection of two thick blood
      smear microscopy methods (WHO and Lambarene method) in a research centre in
      Lambarene, Gabon. Duplicates of negative and low parasitaemia thick blood smears
      were read by several microscopists. The mean and standard deviation of the
      results were used to calculate the limit of blank and subsequently the limit of
      detection. RESULTS: The limit of blank was 0 parasites/MUL for both methods. The
      limit of detection was 62 and 88 parasites/MUL for the Lambarene and WHO method,
      respectively. CONCLUSION: With a simple, back-of-the-envelope calculation, the
      performance of two malaria microscopy methods can be measured. These results are
      specific for each diagnostic unit and cannot be generalized but implementation of
      a system to control microscopy performance can improve confidence in
      parasitological results and thereby strengthen malaria control.

PMID- 24929249
TI  - Viscoelastic properties of bovine knee joint articular cartilage: dependency on
      thickness and loading frequency.
AB  - BACKGROUND: The knee is an incongruent joint predisposed to developing
      osteoarthritis, with certain regions being more at risk of cartilage degeneration
      even in non-osteoarthrosed joints.At present it is unknown if knee regions prone
      to cartilage degeneration have similar storage and/or loss stiffness, and
      frequency-dependent trends, to other knee joint cartilage. The aim of this study
      was to determine the range of frequency-dependent, viscoelastic stiffness of
      articular cartilage across the bovine knee joint. Such changes were determined at
      frequencies associated with normal and rapid heel-strike rise times. METHODS:
      Cartilage on bone, obtained from bovine knee joints, was tested using dynamic
      mechanical analysis (DMA). DMA was performed at a range of frequencies between 1
      and 88 Hz (i.e. relevant to normal and rapid heel-strike rise times).
      Viscoelastic stiffness of cartilage from the tibial plateau, femoral condyles and
      patellar groove were compared. RESULTS: For all samples the storage stiffness
      increased, but the loss stiffness remained constant, with frequency. They were
      also dependent on cartilage thickness. Both the loss stiffness and the storage
      stiffness decreased with cartilage thickness. Femoral condyles had the thinnest
      cartilage but had the highest storage and loss stiffness. Tibial plateau
      cartilage not covered by the meniscus had the thickest cartilage and lowest
      storage and loss stiffness. CONCLUSION: Differences in regional thickness of knee
      joint cartilage correspond to altered frequency-dependent, viscoelastic
      stiffness.

PMID- 24929250
TI  - Birthplace in New South Wales, Australia: an analysis of perinatal outcomes using
      routinely collected data.
AB  - BACKGROUND: The outcomes for women who give birth in hospital compared with at
      home are the subject of ongoing debate. We aimed to determine whether a
      retrospective linked data study using routinely collected data was a viable means
      to compare perinatal and maternal outcomes and interventions in labour by planned
      place of birth at the onset of labour in one Australian state. METHODS: A
      population-based cohort study was undertaken using routinely collected linked
      data from the New South Wales Perinatal Data Collection, Admitted Patient Data
      Collection, Register of Congenital Conditions, Registry of Birth Deaths and
      Marriages and the Australian Bureau of Statistics. Eight years of data provided a
      sample size of 258,161 full-term women and their infants. The primary outcome was
      a composite outcome of neonatal mortality and morbidity as used in the Birthplace
      in England study. RESULTS: Women who planned to give birth in a birth centre or
      at home were significantly more likely to have a normal labour and birth compared
      with women in the labour ward group. There were no statistically significant
      differences in stillbirth and early neonatal deaths between the three groups,
      although we had insufficient statistical power to test reliably for these
      differences. CONCLUSION: This study provides information to assist the
      development and evaluation of different places of birth across Australia. It is
      feasible to examine perinatal and maternal outcomes by planned place of birth
      using routinely collected linked data, although very large data sets will be
      required to measure rare outcomes associated with place of birth in a low risk
      population, especially in countries like Australia where homebirth rates are low.

PMID- 24929251
TI  - Gene-carbohydrate and gene-fiber interactions and type 2 diabetes in diverse
      populations from the National Health and Nutrition Examination Surveys (NHANES)
      as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE)
      study.
AB  - BACKGROUND: Both environmental and genetic factors impact type 2 diabetes (T2D).
      To identify such modifiers, we genotyped 15 T2D-associated variants from genome
      wide association studies (GWAS) in 6,414 non-Hispanic whites, 3,073 non-Hispanic
      blacks, and 3,633 Mexican American participants from the National Health and
      Nutrition Examination Surveys (NHANES) and evaluated interactions between these
      variants and carbohydrate intake and fiber intake. RESULTS: We calculated a
      genetic risk score (GRS) with the 15 SNPs. The odds ratio for T2D with each GRS
      point was 1.10 (95% CI: 1.05-1.14) for non-Hispanic whites, 1.07 (95% CI: 1.02
      1.13) for non-Hispanic blacks, and 1.11 (95% CI: 1.06-1.17) for Mexican
      Americans. We identified two gene-carbohydrate interactions (P < 0.05) in non
      Hispanic whites (with CDKAL1 rs471253 and FTO rs8050136), two in non-Hispanic
      blacks (with IGFBP2 rs4402960 and THADA rs7578597), and two in Mexican Americans
      (with NOTCH2 rs1092398 and TSPAN8-LGRS rs7961581). We found three gene-fiber
      interactions in non-Hispanic whites (with ADAMT59 rs4607103, CDKN2A/2B rs1801282,
      and FTO rs8050136), two in non-Hispanic blacks (with ADAMT59 rs4607103 and THADA
      rs7578597), and two in Mexican Americans (with THADA rs7578597 and TSPAN8-LGRS
      rs796158) at the P < 0.05 level. Interactions between the GRS and nutrients
      failed to reach significance in all the racial/ethnic groups. CONCLUSION: Our
      results suggest that dietary carbohydrates and fiber may modify T2D-associated
      variants, highlighting the importance of dietary nutrients in predicting T2D
      risk.

PMID- 24929252
TI  - The long-term effect of community-based health management on the elderly with
      type 2 diabetes by the Markov modeling.
AB  - The aim of this study was to assess the long-term effects of community-based
      health management on elderly diabetic patients using a Markov model. A Markov
      decision model was used to simulate the natural history of diabetes. Data were
      obtained from our randomized trials of elderly with type 2 diabetes and from the
      published literature. One hundred elderly patients with type 2 diabetes were
      randomly allocated to either the management or the control group in a one-to-one
      ratio. The management group participated in a health management program for 18
      months in addition to receiving usual care. The control group only received usual
      care. Measurements were performed on both groups at baseline and after 18 months.
      The Markov model predicted that for every 1000 diabetic patients receiving health
      management, approximately 123 diabetic patients would avoid complications, and
      approximately 37 would avoid death over the next 13 years. The results suggest
      that the health management program had a positive long-term effect on the health
      of elderly diabetic patients. The Markov model appears to be useful in health
      care planning and decision-making aimed at reducing the financial and social
      burden of diabetes. 

PMID- 24929253
TI  - The clinical relevance of dry powder inhaler performance for drug delivery.
AB  - BACKGROUND: Although understanding of the scientific basis of aerosol therapy
      with dry powder inhalers (DPIs) has increased, some misconceptions still persist.
      These include the beliefs that high resistance inhalers are unsuitable for some
      patients, that extra fine (<1.0 MUm) particles improve peripheral lung deposition
      and that inhalers with flow rate-independent fine particle fractions (FPFs)
      produce a more consistent delivered dose to the lungs. OBJECTIVES: This article
      aims to clarify the complex inter-relationships between inhaler design and
      resistance, inspiratory flow rate (IFR), FPF, lung deposition and clinical
      outcomes, as a better understanding may result in a better choice of DPI for
      individual patients. METHODS: The various factors that determine the delivery of
      drug particles into the lungs are reviewed. These include aerodynamic particle
      size distribution, the inspiratory manoeuvre, airway geometry and the three basic
      principles that determine the site and extent of deposition: inertial impaction,
      sedimentation and diffusion. DPIs are classed as either dependent or independent
      of inspiratory flow rate and vary in their internal resistance to inspiration.
      The effects of these characteristics on drug deposition in the airways are
      described using data from studies directly comparing currently available inhaler
      devices. RESULTS: Clinical experience shows that most patients can use a high
      resistance DPI effectively, even during exacerbations. Particles in the
      aerodynamic size range from 1.5-5 MUm are shown to be optimal, as particles <1.0
      MUm are very likely to be exhaled again while those >5 MUm may impact on the
      oropharynx. For DPIs with a constant FPF at all flow rates, less of the delivered
      dose reaches the central and peripheral lung when the flow rate increases,
      risking under-dosing of the required medication. In contrast, flow rate-dependent
      inhalers increase their FPF output at higher flow rates, which compensates for
      the greater impaction on the upper airways as flow rate increases. CONCLUSIONS:
      The technical characteristics of different inhalers and the delivery and
      deposition of the fine particle dose to the lungs may be important additional
      considerations to help the physician to select the most appropriate device for
      the individual patient to optimise their treatment.

PMID- 24929254
TI  - Downregulation of PPARgamma by miR-548d-5p suppresses the adipogenic
      differentiation of human bone marrow mesenchymal stem cells and enhances their
      osteogenic potential.
AB  - BACKGROUND: Human bone marrow mesenchymal stem cells (hBMSCs) are multipotent
      cells that can differentiate into a variety of cell types. Elevated expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) promotes the
      adipogenic differentiation of hBMSCs, and reduces their osteogenic
      differentiation. MicroRNAs (miRNAs) have been shown to play important roles in
      the regulation of hBMSCs differentiation. Because bioinformatic analysis has
      indicated that PPARgamma is a candidate target of miR-548d-5p, the aim of this
      study was to assess the impact of miR-548d-5p on the dexamethasone-induced
      adipogenic differentiation of hBMSCs. METHODS: A quantitative RT-PCR (qRT-PCR)
      assay was used to compare miR-548d-5p expression levels in dexamethasone-induced
      hBMSCs and uninduced control cells. Oil red O staining, cellular triglyceride
      (TG) content, and the mRNA and protein levels of PPARgamma and CCAAT/enhancer
      binding protein alpha (C/EBPalpha) were used to evaluate the adipogenic
      differentiation of hBMSCs. Alkaline phosphatase (ALP) activity and levels of
      osteocalcin (OCN) and Runx2 were used to evaluate the osteogenic potential of
      hBMSCs. RESULTS: Compared with untreated cells, miR-548d-5p expression levels
      were downregulated during dexamethasone-induced adipogenic differentiation of
      hBMSCs. In contrast to the profuse Oil Red O staining in the cytoplasm of
      dexamethasone + scrambled miRNA-treated cells, there was limited staining in the
      cytoplasm of dexamethasone + miR-548d-5p-treated cells, indicating the absence of
      adipocytes. Moreover, compared with scrambled miRNA-treated cells, treatment with
      miR-548d-5p suppressed cellular levels of PPARgamma and C/EBPalpha mRNA and
      protein, and cell TG content (P < 0.05). In contrast, compared with scrambled
      miRNA-treated cells, cellular levels of OCN and Runx2 mRNA and protein, as well
      as ALP activity, were significantly higher in miR-548d-5p-treated cells (P <
      0.05). Western blot and luciferase reporter assays confirmed that miR-548d-5p
      directly targeted the 3'-untranslated region of PPARgamma. CONCLUSIONS: miR-548d
      5p is downregulated during dexamethasone-induced adipogenic differentiation of
      hBMSCs. By directly targeting and downregulating PPARgamma, miR-548d-5p
      suppresses the dexamethasone-induced adipogenic differentiation of hBMSCs and
      enhances their osteogenic potential. Our findings suggest that miR-548d-5p has
      potential in the treatment of corticosteroid-induced osteonecrosis of the femoral
      head.

PMID- 24929255
TI  - Foreword to the Virus Research special issue on "hantaviruses".

PMID- 24929256
TI  - [Cardiac tamponade after withdrawal of a peripheral access central catheter].
AB  - Central venous catheterization is a very common technique, although its
      complications can be multiple and sometimes fatal. A case is presented of cardiac
      tamponade by parenteral nutrition a few hours after moving a central venous
      catheter peripherally inserted a few days before. The diagnosis was made by
      echocardiography, and an emergency pericardiocentesis was performed, achieving
      complete recovery of the patient. Peripherally inserted central venous catheters
      are more likely to change their position secondary to the movements of the
      patient's arm, thus it is important to use soft catheters, make sure the tip lies
      above the carina to avoid perforation of the pericardial reflexion, and fix it
      well to the skin. Diagnosis must be made as soon as possible, given the high
      mortality rate of this complication, and the essential diagnostic tool is
      echocardiography. Elective treatment consists of early catheter withdrawal and
      emergency pericardiocentesis. 

PMID- 24929257
TI  - Phonatory outcome of 585 nm/pulsed-dye laser in the management of glottic
      leukoplakia.
AB  - OBJECTIVE: Vocal cord mucosectomy using pulsed-dye laser was assessed for its
      ability to completely remove lesions without deterioration of vocal quality in
      cases of vocal cord leukoplakia. To confirm the validity of a pulsed-dye laser,
      we retrospectively analyzed the treatment outcomes of patients who received
      surgery preceded by pulsed-dye laser and compared these with the outcomes of
      patients who received vocal cord mucosectomy using CO2 laser. METHODS: Between
      February 2007 and June 2012, 36 patients were enrolled. Seventeen patients
      received vocal cord treatment with a CO2 laser and 19 patients received operation
      with a pulsed-dye laser. To evaluate voice status, acoustic wave form analysis
      and electroglottography were done, and voice handicap index was measured before
      and after the operation. RESULTS: The entire lesion was removed in all patients.
      Compared to preoperative vocal parameters, the postoperative values for jitter
      were only improved in the pulsed-dye laser group. On stroboscopic findings, a
      diminution or lack of mucosal wave was observed in more CO2 laser cases than
      pulsed-dye laser cases. Significant improvement in voice handicap index results
      was only observed in the pulsed-dye laser group. CONCLUSION: Although long-term
      results with more patients are required to establish the validity of pulsed-dye
      laser, this study confirmed the merits of pulsed-dye laser for the en-bloc
      removal of vocal cord leukoplakia and improved voice outcome.

PMID- 24929259
TI  - Psychosis in children with systemic lupus erythematosus: the role of steroids as
      both treatment and cause.
AB  - Steroids may both be a cause of and treatment for pediatric patients with
      systemic lupus erythematosus (SLE) presenting with psychotic symptoms. We present
      two cases demonstrating that careful histories (including prior steroid exposure)
      and the use of biomarkers can help guide the management of children with SLE
      presenting with psychosis. 

PMID- 24929258
TI  - Elevated early follicular progesterone levels and in vitro fertilization
      outcomes: a prospective intervention study and meta-analysis.
AB  - OBJECTIVE: To assess the impact of elevated early follicular progesterone (P)
      levels in gonadotropin-releasing hormone (GnRH) antagonist cycles on clinical
      outcome using prospective data in combination with a systematic review and meta
      analysis. DESIGN: Nested study within a multicenter randomized controlled trial
      and a systematic review and meta-analysis. SETTING: Reproductive medicine center
      in an university hospital. PATIENT(S): 158 in vitro
      fertilization/intracytoplasmic sperm injection (IVF-ICSI) patients.
      INTERVENTION(S): Recombinant follicle-stimulating hormone (FSH) (150-225 IU)
      administered daily from cycle day 2 onward; GnRH antagonist treatment randomly
      started on cycle day 2 or 6; assignment into two groups according to P level on
      cycle day 2: normal or elevated (>4.77 nmol/L or >1.5 ng/mL, respectively). MAIN
      OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) per started cycle. RESULT(S):
      The incidence of elevated P was 13.3%. A non-statistically-significant difference
      in OPR was present between the normal and elevated P groups (27.0% vs. 19.0%). No
      differential impact of early or late GnRH antagonist initiation on the effect of
      elevated or normal P on OPR was observed. A systematic search of Medline and
      EMBASE from 1972-2013 was performed to identify studies analyzing elevated early
      P levels in GnRH antagonists. The meta-analysis (n=1,052) demonstrated that
      elevated P levels statistically significantly decreased the OPR with 15% (95% CI 
      23, -7 %). Heterogeneity across the studies, presumably based on varying
      protocols, may have modulated the effect of elevated P. CONCLUSION(S): From the
      present meta-analysis it appears that early elevated P levels are associated with
      a lower OPR in GnRH antagonists. The incidence of such a condition, however, is
      low. CLINICAL TRIAL REGISTRATION NUMBER: NCT00866034.

PMID- 24929260
TI  - Letter from the editor: the great mimickers in radiology.

PMID- 24929261
TI  - Tuberculosis--the great mimicker.
AB  - Tuberculosis is an immense health problem in the developing world, and it remains
      a health care challenge in the developed world. It can affect virtually any organ
      system in the body. Diagnosis of tuberculosis is often difficult. Many patients
      with tuberculosis present with nonspecific symptoms, negative purified protein
      derivative skin test result, and negative findings on culture specimens. Cross
      sectional imaging with ultrasound, multidetector computed tomography, and
      magnetic resonance imaging plays an important role in the diagnosis of
      tuberculosis. Tuberculosis demonstrates a variety of radiologic features
      depending on the organ involved and can mimic a number of other disease entities.
      Cross-sectional imaging alone is insufficient in reaching a conclusive diagnosis.
      Tuberculosis is a great mimicker as its radiologic manifestations can simulate
      numerous other diseases across the body systems. However, recognition and
      understanding of the common and uncommon radiologic manifestations of
      tuberculosis should alert considering tuberculosis in the high-risk population
      and correct clinical setting to enable appropriate treatment. 

PMID- 24929262
TI  - Sarcoidosis--the greatest mimic.
AB  - Little is known regarding the exact pathogenesis of sarcoidosis, but it is widely
      recognized that it affects multiple organs. The presentation and imaging features
      can be nonspecific, and this is the reason why it is a great mimic of other
      diseases. Diagnosis of sarcoidosis is often prompted initially by clinical
      suspicion. Imaging plays a crucial role in both detection and monitoring of
      disease process. This review is a case-based systemic approach looking at various
      systemic manifestation of the disease presenting real clinical encounters using
      various imaging modalities. 

PMID- 24929263
TI  - Amyloidosis: review and imaging findings.
AB  - Amyloidosis is a collection of pathophysiologically related disease entities
      caused by the extracellular deposition of abnormal fibrillar proteins called
      amyloid. The accumulation of amyloid may be systemic, involving many organs, or
      localized manifesting as infiltration of individual organs, or in the form of a
      focal, tumorlike lesion. Amyloidosis may develop in the setting of underlying
      conditions, usually chronic inflammatory diseases, in which case it is termed
      secondary, or it may involve no underlying disease and thus be primary or
      idiopathic. Amyloid infiltration leads to pathology through the disruption of
      normal tissue structure and function or through cytotoxic effects of intermediate
      forms of protein aggregates. Clinical manifestations of the disease vary and are
      nonspecific, increasing the need of imaging during the investigation of the
      disease. Imaging findings are diverse and not pathognomonic; however, combined
      with the patient's clinical history they can raise the suspicion of amyloidosis
      and direct toward its confirmation by biopsy. Radiologists should be familiar
      with the appearance of amyloidosis in various modalities to aid the early
      identification of the disease and direct toward prompt treatment planning. Such
      knowledge would provide the radiologist with an opportunity to contribute to
      patient care and aid reducing the high morbidity and mortality of the disease. 

PMID- 24929265
TI  - Extramedullary hemopoiesis.
AB  - Various chronic hematologic disorders that lead to ineffective hemopoiesis or
      inadequate bone marrow function (ie, chronic hemolytic anemias, thalassemia,
      sickle cell anemia, myelofibrosis of many causes, lymphoma, and leukemia) can
      potentially precipitate extramarrow new blood element creation. Extramarrow soft
      tissue that produces blood elements is called extramedullary hemopoietic tissue
      and the process extramedullary hemopoiesis (EMH). Sites commonly involved by EMH
      include the liver, spleen, lymph nodes, and most commonly, paravertebral regions,
      although other sites can sometimes be involved. Physicians rarely consider EMH in
      their differential diagnosis even in cases where it is warranted (diseases of
      ineffective erythropoiesis). This is likely because of the rarity of the
      condition and because imaging findings are nonspecific. We present here a
      systematic review of the imaging findings in EMH. 

PMID- 24929264
TI  - IgG4-related disease in the abdomen: a great mimicker.
AB  - IgG4-related disease is a systemic disorder that can involve various abdominal
      organs. Abdominal manifestations include autoimmune pancreatitis, sclerosing
      cholangitis, gallbladder pseudotumours, multifocal renal abnormalities,
      retroperitoneal fibrosis, and sclerosing mesenteritis. Radiological appearances
      of the IgG4-related disease often resemble malignant tumors and other
      inflammatory processes, potentially leading to unnecessary invasive procedures.
      Moreover, a timely diagnosis of IgG4-related disease leads to an effective
      treatment with steroids. Therefore, it is important to understand the spectrum of
      imaging manifestations of IgG4-related disease and their differentiating features
      from other diagnoses. 

PMID- 24929266
TI  - The great mimickers: Castleman disease.
AB  - Castleman disease (CD) was first described and most commonly occurs in the form
      of classic hyaline-vascular-type CD with hyperenhancing localized (unicentric)
      nonneoplastic lymphadenopathy. CD may affect any body region including unusual
      locations for isolated lymph node enlargement. This makes CD a great mimicker of
      more common benign and malignant masses in the neck, chest, abdomen, and pelvis.
      CD masses commonly raise the suspicion of lymphoma, paraganglioma, neuroendocrine
      tumor, metastatic adenopathy, solid parenchymal tumors, and infectious or
      inflammatory diseases. The less common plasma cell-type CD, mixed CD, and human
      herpes virus-8-associated CD (HHV8-CD) are more prone to lead to generalized
      (multicentric) adenopathy without the typical nodal hyperenhancement and are
      associated with B symptoms and hematologic and immunologic manifestations. The
      generalized forms of CD have a worse prognosis, which can approach that of
      malignancies. CD has multiple known associations with neoplasms, skin diseases,
      blood dyscrasias, and immunodeficiency, which include certain forms of lymphoma;
      paraneoplastic pemphigus; polyneuropathy, organomegaly, endocrinopathy, M
      protein, and skin changes syndrome; and plasma cell dyscrasias. Cytokine
      overproduction (IL-6) is an important pathogenetic factor in the development of
      CD. The treatment is accordingly variable, from curative or diagnostic resection
      of a solitary lesion to systemic chemotherapy or anti-IL-6 therapy. 

PMID- 24929267
TI  - Metastatic melanoma in the chest and abdomen: the great radiologic imitator.
AB  - Metastatic melanoma causes an unpredictable variety of manifestations in the
      chest and abdomen that may be indistinguishable from other diseases by imaging
      alone. Melanoma metastases commonly involve the lymph nodes, lungs, liver, and
      small bowel, but virtually any organ can be affected. Newer modalities, such as
      contrast-enhanced ultrasound and whole-body magnetic resonance imaging, may
      provide more sensitive detection of metastatic melanoma for diagnosis, staging,
      and surveillance. An understanding of the predominantly hematogenous nature of
      metastatic spread by melanoma as well as a high index of suspicion in any patient
      with a history of melanoma may allow for more precise and confident diagnosis. 

PMID- 24929268
TI  - Malignant and benign lesions of the skeletal musculature.
AB  - There are several tumors and tumorlike conditions with variable biological
      behavior that may involve the skeletal musculature. The aim of this work was to
      review different intramuscular lesions and to provide a classification of muscle
      lesions based on their radiological patterns as well as to provide as a pictorial
      essay the imaging characteristics of typical muscle lesions. Radiologically,
      intramuscular lesions can manifest as solid masses, liquid or semiliquid masses,
      fat-containing lesions, diffuse muscle enlargement, and muscle calcifications.
      Additionally, lesions with mixed patterns can also occur. It is noteworthy that
      different malignant or benign muscle lesions can manifest with identical
      radiological patterns. 

PMID- 24929269
TI  - The renal sinus--transitional cell carcinoma and its mimickers on computed
      tomography.
AB  - The renal sinus is a deep recess located at the medial aspect of the kidney
      surrounded by the renal parenchyma. It contains within it the collecting system
      of the kidney, lymphatics, nerves, and renal blood vessels. The remainder of the
      sinus is filled with adipose and fibrous tissue. A variety of pathological
      conditions arise from the different tissues in this site. The aim of this review
      is to explore and illustrate the common and less common processes affecting the
      renal pelvis. 

PMID- 24929270
TI  - Variability of weight loss results with Roux-en-Y gastric bypass.

PMID- 24929271
TI  - Survey of women's experiences of care in a new freestanding midwifery unit in an
      inner city area of London, England: 2. Specific aspects of care.
AB  - OBJECTIVE: to describe and compare women's experiences of specific aspects of
      maternity care before and after the opening of the Barkantine Birth Centre, a new
      freestanding midwifery unit in an inner city area. DESIGN: telephone surveys
      undertaken in late pregnancy and about six weeks after birth. Two separate waves
      of interviews were conducted, Phase 1 before the birth centre opened and Phase 2
      after it had opened. SETTING: Tower Hamlets, a deprived inner city borough in
      east London, 2007-2010. PARTICIPANTS: 620 women who were resident in Tower
      Hamlets and who satisfied the Barts and the London Trust's eligibility criteria
      for using the birth centre. Of these, 259 women were recruited to Phase 1 and 361
      to Phase 2. MEASUREMENTS AND FINDINGS: the replies women gave show marked
      differences between the model of care in the birth centre and that at the
      obstetric unit at the Royal London Hospital with respect to experiences of care
      and specific practices. Women who initially booked for birth centre care were
      more likely to attend antenatal classes and find them useful and were less likely
      to be induced. Women who started labour care at the birth centre in spontaneous
      labour were more likely to use non-pharmacological methods of pain relief, most
      notably water and less likely to use pethidine than women who started care at the
      hospital. They were more likely to be able to move around in labour and less
      likely to have their membranes ruptured or have continuous CTG. They were more
      likely to be told to push spontaneously when they needed to rather than under
      directed pushing and more likely to report that they had been able to choose
      their position for birth and deliver in places other than the bed, in contrast to
      the situation at the hospital. The majority of women who had a spontaneous onset
      of labour delivered vaginally, with 28.6 per cent of women at the birth centre
      but no one at the hospital delivering in water. Primiparous women who delivered
      at the birth centre were less likely to have an episiotomy. Most women who
      delivered at the birth centre reported that they had chosen whether or not to
      have a physiological third stage, whereas a worrying proportion at the hospital
      reported that they had not had a choice. A higher proportion of women at the
      birth centre reported skin to skin contact with their baby in the first two hours
      after birth. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: significant
      differences were reported between the hospital and the birth centre in practices
      and information given to the women, with lower rates of intervention, more choice
      and significant differences in women's experiences. This case study of a single
      inner-city freestanding midwifery unit, linked to the Birthplace in England
      Research Programme, indicates that this model of care also leads to greater
      choice and a better experience for women who opted for it.

PMID- 24929272
TI  - A feminist narrative study of the maternity care experiences of women who were
      sexually abused in childhood.
AB  - BACKGROUND: One in five women experience childhood sexual abuse and these women
      may suffer trauma during childbirth. Their maternity care is often reminiscent of
      their abuse. OBJECTIVE: To inform practice by exploring the impact that childhood
      sexual abuse has on the maternity care experiences of adult women. DESIGN: This
      was a narrative study from a feminist perspective. The part of the study reported
      here utilised in-depth interviews with women. Data were analysed using the Voice
      Centred Relational Method of analysis and further thematic analysis. SETTING:
      Users of one maternity service in the South of England PARTICIPANTS: Nine women
      were interviewed following purposive sampling. FINDINGS: The main themes
      identified were women's narratives of self, women's narratives of relationship,
      women's narratives of context and the childbirth journey. The concept of silence
      linked all these themes and aspects of the study relating to it are reported
      here. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Every day midwives will
      encounter women who were sexually abused in childhood. Most of these women do not
      disclose to those caring for them and may not respond to a direct question. They
      will not necessarily be distinguishable from other women accessing maternity
      services but they may find their experiences deeply traumatic. Silence is a
      challenge for those providing their care. Open communication and a genuine
      interest in women as individuals are required. Midwives need to listen for the
      unspoken messages women are trying to convey. If all women were treated with
      dignity and respect more may emerge from the experience of childbirth feeling
      empowered rather than violated.

PMID- 24929273
TI  - [Ophthalmology, history and humanities].

PMID- 24929274
TI  - [The eye of the man with the camera].

PMID- 24929275
TI  - [Human immunodeficiency virus infection in Spain: it is time to act].

PMID- 24929276
TI  - Investigating how implementation intentions improve non-focal prospective memory
      tasks.
AB  - Implementation intentions are a self-regulatory strategy broadly studied in the
      area of social cognition that can improve realization of one's goals and improve
      performance on prospective memory tasks. Three experiments, using a non-focal
      task for which the prospective memory targets were specified at the time of
      intention formation, investigated whether (and how) implementation intentions can
      improve non-focal prospective memory performance. An improvement in prospective
      memory performance was accompanied by an increase in the allocation of conscious
      resources to the prospective memory task, but not by an increase in perceived
      importance of the prospective memory task. The third experiment also investigated
      the effects of implementation intentions on recall of the appropriate action and
      found that accurate action recall was improved by implementation intentions.
      Finally, the effect of implementation intention instructions on cognitive
      processes that underlie non-focal prospective memory performance was investigated
      using a multinomial model. 

PMID- 24929277
TI  - Learning a keying sequence you never executed: evidence for independent
      associative and motor chunk learning.
AB  - A substantial amount of research has addressed how people learn and control
      movement sequences. Recent results suggested that practice with discrete key
      pressing sequences results in two types of sequence learning: associative
      learning and motor chunk development (Verwey & Abrahamse, 2012). In the present
      study, we addressed whether in keying sequences of limited length associative
      learning develops also when the use of the chunking mode is prevented by
      introducing during practice random deviants. In line with the notion of two
      different learning mechanisms, the present results indicate that associative
      sequence learning develops when motor chunks cannot be developed during practice.
      This confirms the notion that motor chunks do not rely on these associations. In
      addition, experience with a particular execution mode during the practice phase
      seems to benefit subsequent use of that mode with unfamiliar and random
      sequences. Also, participants with substantial video-gaming experience were
      faster in executing discrete keying sequences in the chunking mode. These last
      two results may point to the development of a general ability to produce movement
      sequences in the chunking mode.

PMID- 24929278
TI  - Effects of ammonium carbonate pretreatment on the enzymatic digestibility and
      structural features of rice straw.
AB  - Rice straw was pretreated with ammonium carbonate ((NH4)2CO3), a major
      intermediate of ammonia-based carbon capture process, and evaluated for the
      effects of critical pretreatment parameters including (NH4)2CO3 concentration (5
      25%), temperature (60-90 degrees C), and reaction time (4-24 h) on enzymatic
      digestibility. Pretreatment of rice straw at 80 degrees C for 12 h using 20%
      (NH4)2CO3 and 1:10 solid to liquid ratio resulted in enzymatic digestibility of
      72.2%, which was higher than that pretreated with the same moles of aqueous
      ammonia. We also investigated physical characteristics of pretreated rice straw,
      including surface area, pore volume and size, crystallinity, and scanning
      electron microscopy image. The ammonium carbonate pretreatment process, as a
      novel pretreatment technique, enhanced enzymatic hydrolysis of lignocellulose by
      altering structural features.

PMID- 24929280
TI  - Assessment and regression analysis on instant catapult steam explosion
      pretreatment of corn stover.
AB  - Instant catapult steam explosion (ICSE) offers enormous physical force on
      lignocellulosic biomass due to its extremely short depressure duration. In this
      article, the response surface methodology was applied to optimize the effect of
      working parameters including pressure, maintaining time and mass loading on the
      crystallinity index and glucose yield of the pretreated corn stover. It was found
      that the pressure was of essential importance, which determined the physical
      force that led to the morphological changes without significant chemical
      reactions, and on the other hand the maintaining time mainly contributed to the
      thermo-chemical reactions. Furthermore, the pretreated biomass was assessed by
      scanning electron microscope, X-ray diffraction and Fourier transform infrared
      spectra to understand mechanisms underlying the ICSE pretreatment. 

PMID- 24929279
TI  - Assessment of energy crops alternative to maize for biogas production in the
      Greater Region.
AB  - The biomethane yield of various energy crops, selected among potential
      alternatives to maize in the Greater Region, was assessed. The biomass yield, the
      volatile solids (VS) content and the biochemical methane potential (BMP) were
      measured to calculate the biomethane yield per hectare of all plant species. For
      all species, the dry matter biomass yield and the VS content were the main
      factors that influence, respectively, the biomethane yield and the BMP. Both
      values were predicted with good accuracy by linear regressions using the biomass
      yield and the VS as independent variable. The perennial crop miscanthus appeared
      to be the most promising alternative to maize when harvested as green matter in
      autumn and ensiled. Miscanthus reached a biomethane yield of 5.5 +/- 1 *
      10(3)m(3)ha(-1) during the second year after the establishment, as compared to
      5.3 +/- 1 * 10(3)m(3)ha(-1) for maize under similar crop conditions.

PMID- 24929281
TI  - Anaerobic digestion of pig and dairy manure under photo-dark fermentation
      condition.
AB  - Anaerobic digestion (AD) with livestock manure is a promising way for biogas
      production. This work presents the influence of photo-dark fermentation on biogas
      production of pig manure (PM) and dairy manure (DM). All sets were conducted with
      temperature 35 +/- 2  degrees C and total solid concentrations 8%: PM1 and DM1 in
      transparent reactor under sunlight for photo-dark fermentation, and PM2 and DM2
      in non-transparent reactor for dark fermentation. DM2 had the best cumulative
      biogas production (CBP) of 15,447.5 mL, followed by PM1 (15,020 mL) with stable
      pH and low total ammonium nitrogen (TAN) concentration (1384.99 mg/L), and DM1
      and PM2. The CBP of DM2 was 5.77 times as much as PM2. The relationship between
      CBP and four factors including volatile fatty acid (VFA), TAN, total alkalinity
      and pH was analyzed. pH gained the maximum determination coefficient with the CBP
      among all sets and total alkalinity showed negative correlation with CBP of PM1
      and DM1.

PMID- 24929282
TI  - Periprosthetic supracondylar femoral fractures above a total knee replacement:
      compatibility guide for fixation with a retrograde intramedullary nail.
AB  - The incidence of total knee arthroplasty (TKA) is increasing, as are
      periprosthetic supracondylar femoral fractures. Treatment is complex and may
      involve the use of a retrograde intramedullary femoral nail, and it is essential
      to know the nail will fit through the femoral prosthesis in line with the
      intramedullary canal. Knowledge of certain measurements is crucial i.e. minimal
      intercondylar distance and the position of the notch on the femoral component in
      relation to the intramedullary canal. A review of TKA prostheses dimensions and
      their compatibility with a retrograde nail was obtained directly from the
      manufacturers. A comprehensive data set lists manufacturer, model, size, minimal
      intercondylar notch distance and position. This will be of practical use when
      planning the operative management of periprosthetic supracondylar femoral
      fractures. 

PMID- 24929283
TI  - Revision total hip arthroplasty with a modular cementless femoral stem.
AB  - We retrospectively reviewed 123 patients who underwent cementless THA with
      modular femoral stem designs for revision THA or conversion of failed ORIF and
      found 75 patients available for analysis. The Harris Hip Score (HHS) improved
      from 52 +/- 14 to 86 +/- 11 (P < 0.001). The femoral stem was re-revised in eight
      patients (11%). The mean time to re-revision was 1.1years (0.13-2.54). Reasons
      for re-revision included infection (n = 5, 7%), aseptic loosening (n = 2, 3%) and
      significant pain (n = 1, 1%). There were no failures of the modular junctions. PC
      stems had an increased rate of intraoperative fractures (PC 28% vs. STS 9%, P =
      0.04). Modular cementless femoral stems provide acceptable mid-term results in
      revision THA. 

PMID- 24929284
TI  - Cholesterol modulates LRP5 expression in the vessel wall.
AB  - OBJECTIVE: Macrophages are key players in atherosclerotic lesion formation and
      progression. We have recently demonstrated that lipid-loaded macrophages show
      activation of the canonical Wnt signaling pathway. METHODS: To test the in vivo
      role of the canonical Wnt pathway in atherosclerosis we used mice deficient in
      the Wnt signaling receptor LRP5 (LRP5(-/-)) fed a hypercholesterolemic diet (HC)
      to induce atherosclerosis. These dietary groups were further subdivided into two
      subgroups receiving their respective diets supplemented with 2% plant sterol
      esters (PSE). All mice remained on their assigned diets until age 18 weeks.
      RESULTS: HC WT mice had mildly increased non-HDL cholesterol levels, developed
      aortic atherosclerotic lesions and showed upregulated expression levels of aortic
      Lrp5. HC LRP5(-/-) mice develop larger aortic atherosclerotic lesions than WT
      mice indicating that LRP5 has a protective function in atherosclerosis
      progression. The oral administration of PSE, a dietary cholesterol-lowering
      agent, had an effect in the expression levels of the Wnt signaling receptor and
      in atherosclerosis progression. We found that PSE reduced serum total cholesterol
      levels, abolished HC-induced LRP5 overexpression and reduced aortic
      atherosclerotic plaques. CONCLUSION: The proatherogenic effects of the excess of
      plasma lipids are in part mediated by modulation of LRP5 in the aorta. LRP5 and
      canonical Wnt signaling exert a protective defense mechanism against
      hyperlipidemia and atherosclerosis lesion progression.

PMID- 24929285
TI  - Determinants of cerebrovascular remodeling: do large brain arteries accommodate
      stenosis?
AB  - OBJECTIVE: It is hypothesized that outward remodeling in systemic arteries is a
      compensatory mechanism for lumen area preservation in the face of increasing
      arterial stenosis. Large brain arteries have also been studied, but it remains
      unproven if all assumptions about arterial remodeling can be replicated in the
      cerebral circulation. METHODS: The sample included 196 autopsied subjects with a
      mean age of 55 years; 63 % were men, and 74 % non-Hispanic whites. From each of
      1396 dissected cadaveric large arteries of the circle of Willis, the areas of the
      lumen, intima, media, and adventitia were measured. Internal elastic lamina (IEL)
      area was defined as the area encircled by this layer. Stenosis was calculated by
      dividing the plaque area by the IEL area and multiplying by 100. RESULTS:
      Plotting stenosis against lumen area or stratified by arterial size showed no
      preservation of the lumen in the setting of growing stenosis. We could not find
      an association between greater IEL proportion and stenosis (B = 0.44, P = 0.86).
      Stratifying arteries by their size, we found that smaller arteries have greater
      lumen reduction at any degree of stenosis (B = -23.65, P <= 0.0001), and although
      larger arteries show a positive association between IEL proportion and stenosis,
      this was no longer significant after adjusting for covariates (B = 6.0, P =
      0.13). CONCLUSIONS: We cannot confirm the hypothesis that large brain arteries
      undergo outward remodeling as an adaptive response to increasing degrees of
      stenosis. We found that the lumen decreases proportionally to the degree of
      stenosis.

PMID- 24929286
TI  - The inverse association of incident cardiovascular disease with plasma bilirubin
      is unaffected by adiponectin.
AB  - OBJECTIVE: Bilirubin may protect against atherosclerotic cardiovascular disease
      (CVD). The heme oxygenase pathway is crucial for bilirubin generation, and is
      stimulated by adiponectin. We tested the relationship of plasma bilirubin with
      adiponectin, and determined whether the association of incident CVD with
      bilirubin is modified by adiponectin. METHODS: A community-based prospective
      nested case-control study (PREVEND cohort) was carried out in 87 non-diabetic men
      who developed a first cardiovascular event (cases) and 94 controls during a
      median follow-up of 6.1 (2.8-10.6) years. RESULTS: In all subjects combined,
      bilirubin was positively related to adiponectin (r = 0.205, P = 0.006). Age
      adjusted incident CVD was inversely associated with bilirubin (hazard ratio (HR):
      0.80 (95% CI 0.65-0.99), P = 0.048), independently of adiponectin (HR: 0.78 (95%
      CI 0.63-0.97), P = 0.027). Adiponectin did not modify the association of CVD with
      bilirubin (interaction term: P = 0.65). After additional adjustment for CVD risk
      factors, neither the association of incident CVD with bilirubin nor with
      adiponectin remained significant (P > 0.20 for both), and there was again no
      interaction between bilirubin and adiponectin on CVD risk (P = 0.67). CONCLUSION:
      Bilirubin is related to adiponectin, but the association of bilirubin with CVD
      risk is largely unaffected by adiponectin.

PMID- 24929288
TI  - Synthesis and antimicrobial activity of amine linked bis- and tris-heterocycles.
AB  - A series of amine linked bis- and tris-heterocycles were prepared from heteroaryl
      cinnamamides and tested for antimicrobial activity. The compounds 11c and 12c
      exhibited excellent antibacterial activity while 12a and 12c displayed excellent
      antifungal activity. 

PMID- 24929287
TI  - Lipoprotein-associated phospholipase A2 and risk of dementia in the
      Cardiovascular Health Study.
AB  - OBJECTIVE: To evaluate associations between Lipoprotein-associated phospholipase
      A2 (Lp-PLA2) mass and activity with risk of dementia and its subtypes. METHODS:
      Analysis were completed on 3320 participants of the Cardiovascular Health Study
      (CHS), a population-based longitudinal study of community-dwelling adults age
      >=65 years followed for an average of 5.4 years. Baseline serum Lp-PLA2 mass was
      measured using a sandwich enzyme immunoassay and Lp-PLA2 activity utilized a
      tritiated-platelet activating factor activity assay. Cox proportional hazards
      regression assessed the relative risk of incident dementia with higher baseline
      Lp-PLA2 adjusting for demographics, cardiovascular disease (CVD) and risk
      factors, inflammation markers and apolipoprotein E (APOE) genotype. RESULTS: Each
      standard deviation higher Lp-PLA2 mass and activity were related to increased
      risk of dementia (fully adjusted HR: 1.11 per SD, 95% CI: 1.00-1.24 for mass; HR:
      1.12 per SD, 95% CI: 1.00-1.26 for activity). Persons in the highest quartile of
      Lp-PLA2 mass were 50% more likely to develop dementia than those in the lowest
      quartile in adjusted models (HR: 1.49; 95% CI: 1.08-2.06). Among dementia
      subtypes, the risk of AD was increased two-fold in the highest compared to lowest
      quartile of Lp-PLA2 mass (adjusted HR: 1.98, 95% CI: 1.22-3.21). Results were
      attenuated in models of mixed dementia and VaD. Lp-PLA2 activity also doubled the
      risk of mixed dementia in the highest compared to lowest quartile (HR: 2.21, 95%
      CI: 1.12-4.373). INTERPRETATION: These data support Lp-PLA2 as a risk factor for
      dementia independent of CVD and its risk factors. Further study is required to
      clarify the role of Lp-PLA2-related mechanisms in dementia subtypes.

PMID- 24929289
TI  - Design, synthesis and pharmacological evaluation of novel substituted quinoline-2
      carboxamide derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors
      and anticancer agents.
AB  - In continuation of our research for novel human dihydroorotate dehydrogenase
      (hDHODH) inhibitors, herein we reported design, synthesis and pharmacological
      evaluation of novel substituted quinoline-2-carboxamide derivatives. Human DHODH
      enzyme inhibition assay was used to screen the synthesized compounds as hDHODH
      inhibitors. The synthesized compounds were also evaluated for their
      antiproliferative effects on the cancer cell lines (HEP-3B and A-375) to
      establish a proof as anticancer agents. The chemical structures of compounds were
      confirmed by (1)H, (13)C NMR, IR, MS and elemental analysis. The purity of
      compounds was also checked by HPLC analysis. Compounds with bulky groups (-OCH3, 
      OCF3 and -CF3) at C6-position of quinoline ring showed good activity. 

PMID- 24929290
TI  - Inhibition of 17beta-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones
      and discovery of new potent inhibitors with thioether linker.
AB  - Estradiol is the most potent estrogen in humans. It is known to be involved in
      the development and proliferation of estrogen dependent diseases such as breast
      cancer and endometriosis. The last step of its biosynthesis is catalyzed by
      17beta-hydroxysteroid dehydrogenase type 1 (17beta- HSD1) which consequently is a
      promising target for the treatment of these diseases. Recently, we reported on
      bicyclic substituted hydroxyphenylmethanones as potent inhibitors of 17beta-HSD1.
      The present study focuses on rational structural modifications in this compound
      class with the aim of gaining more insight into its structure-activity
      relationship (SAR). (4-Hydroxyphenyl)-(5-(3-hydroxyphenylsulfanyl)-thiophen-2
      yl)methanone (25) was discovered as a member of a novel potent class of human
      17beta-HSD1 inhibitors. Computational methods were used to elucidate its
      interactions with the target protein. The compound showed activity also towards
      the murine 17beta-HSD1 enzyme and thus is a starting point for the design of
      compounds suitable for evaluation in an animal disease model. 

PMID- 24929291
TI  - Synthesis, biological evaluation and structure-activity relationships of new
      phthalazinedione derivatives with vasorelaxant activity.
AB  - Five series of 1,4-phthalazinedione derivatives were synthesized in good yields.
      Vasorelaxant activity of these new derivatives was measured on either intact or
      endothelium-denuded isolated rat thoracic aortic rings pre-contracted with
      phenylephrine. Most of studied compounds, substituted in both nitrogen atoms,
      attained practically the total relaxation of the organ at low micromolar
      concentrations. The presence of functional endothelium significantly reduced the
      EC50 values for most of studied compounds. Some structure-activity relationships
      were established and compounds 2d and 5d can be considered as new leads for
      further modifications. 

PMID- 24929292
TI  - Design, synthesis and biological evaluation of hybrid bioisoster derivatives of N
      acylhydrazone and furoxan groups with potential and selective anti-Trypanosoma
      cruzi activity.
AB  - Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were
      designed with the objective of obtaining at least a dual mechanism of action:
      cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed
      compounds were synthesized varying the substitution in N-acylhydrazone and in
      furoxan group as well. They had its anti-Trypanosoma cruzi activity in
      amastigotes forms, NO releasing potential and inhibitory cruzain activity
      evaluated. The two most active compounds (6, 14) both in the parasite amastigotes
      and in the enzyme contain the nitro group in para position of the aromatic ring.
      The permeability screening in Caco-2 cell and cytotoxicity assay in human cells
      were performed for those most active compounds and both showed to be less
      cytotoxic than the reference drug, benznidazole. Compound 6 was the most
      promising, since besides activity it showed good permeability and selectivity
      index, higher than the reference drug. Thereby the compound 6 was considered as a
      possible candidate for additional studies. 

PMID- 24929293
TI  - 7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis,
      pharmacological evaluation, molecular modeling and QSAR studies.
AB  - A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was
      synthesized and tested for their ability to inhibit electric eel
      acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum
      butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids
      consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative,
      connected with analogues of N-benzylpiperazine moieties mimicking N
      benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds
      exerted mostly non-selective profile in inhibiting cholinesterases of different
      origin with IC50 ranging from micromolar to sub-micromolar concentration scale.
      Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors
      are capable to simultaneously bind peripheral anionic site (PAS) as well as
      catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies
      were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil
      like derivatives can be considered as interesting candidates for Alzheimer's
      disease treatment.

PMID- 24929294
TI  - Syntheses, characterization and evaluation of novel 2,6-diarylpiperidin-4-ones as
      potential analgesic-antipyretic agents.
AB  - A novel series of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-one
      derivatives (1c-3c and 5c) were synthesized, via base catalyzed nucleophilic
      substitution of N-chloroacetyl-2,6-diarylpiperidin-4-ones (1b-6b) with N-methyl
      piperazine. The newly synthesized compounds were characterized by FTIR, Mass and
      NMR spectral studies. All the compounds were screened for their possible
      analgesic and antipyretic activities. The compound 2c exhibited promising
      antipyretic activity, comparable to that of paracetamol at 60 mg/kg dose. The
      compounds 2b and 2c showed significant analgesic profile at a dose of 60 mg/kg
      and were also found to be more potent than the reference drug, diclofenac sodium.
      Thus, it can be concluded that the synthesized 2,6-diarylpiperidin-4-ones exhibit
      promising antipyretic and analgesic activities and could be potential drug
      candidates.

PMID- 24929295
TI  - [Author's response to article "Bilateral traumatic facial paralysis. Case report"
      by Jose Undabeitia et al].

PMID- 24929296
TI  - The quadricuspid aortic valve.

PMID- 24929297
TI  - Free radical-mediated systemic immunity in plants.
AB  - Systemic acquired resistance (SAR) is a form of defense that protects plants
      against a broad-spectrum of secondary infections by related or unrelated
      pathogens. SAR related research has witnessed considerable progress in recent
      years and a number of chemical signals and proteins contributing to SAR have been
      identified. All of these diverse constituents share their requirement for the
      phytohormone salicylic acid, an essential downstream component of the SAR
      pathway. However, recent work demonstrating the essential parallel functioning of
      nitric oxide (NO)-derived and reactive oxygen species (ROS)-derived signaling
      together with SA provides important new insights in the overlapping pathways
      leading to SAR. This review discusses the potential significance of branched
      pathways and the relative contributions of NO/ROS-derived and SA-derived pathways
      in SAR.

PMID- 24929298
TI  - Broad compatibility in fungal root symbioses.
AB  - Plants associate with a wide range of beneficial fungi in their roots which
      facilitate plant mineral nutrient uptake in exchange for carbohydrates and other
      organic metabolites. These associations play a key role in shaping terrestrial
      ecosystems and are widely believed to have promoted the evolution of land plants.
      To establish compatibility with their host, root-associated fungi have evolved
      diverse colonization strategies with distinct morphological, functional and
      genomic specializations as well as different degrees of interdependence. They
      include obligate biotrophic arbuscular mycorrhizal (AM), and facultative
      biotrophic ectomycorrhizal (ECM) interactions but are not restricted to these
      well-characterized symbioses. There is growing evidence that root endophytic
      associations, which due to their inconspicuous nature have been often overlooked,
      can be of mutualistic nature and represent important players in natural and
      managed environments. Recent research into the biology and genomics of root
      associations revealed fascinating insight into the phenotypic and trophic
      plasticity of these fungi and underlined genomic traits associated with biotrophy
      and saprotrophy. In this review we will consider the commonalities and
      differences of AM and ECM associations and contrast them with root endophytes.

PMID- 24929299
TI  - Influence of ferric oxyhydroxide addition on biomethanation of waste activated
      sludge in a continuous reactor.
AB  - This study investigated the potential of enhancing the activity of iron-reducing
      bacteria (IRBs) to increase the biomethanation rate of waste activate sludge
      (WAS). The effects of biostimulation by ferric oxyhydroxide (Phase 2) and
      bioaugmentation with an enriched IRB consortium (Phase 3) were examined in a
      continuous anaerobic reactor treating WAS. Compared to the control operation
      (Phase 1), significant rises in methane yield (10.8-59.4%) and production rate
      (24.5-52.9%) were demonstrated by the biostimulation and bioaugmentation
      treatments. Visible structural changes were observed in bacterial community with
      the phases while not in archaeal community. Acinetobacter- and Spirochaetales
      related populations were likely the major players driving anaerobic iron
      respiration and thus leading to enhanced biomethanation performance, in Phases 2
      and 3, respectively. Our results suggest an interesting new potential for
      enhancing biomethanation of WAS. 

PMID- 24929300
TI  - Effects of anionic surfactant on extraction of free fatty acid from Chlorella
      vulgaris.
AB  - Microalgal lipid with a high free fatty acid (FFA) content was directly extracted
      from Chlorella vulgaris, using SDBS, in an acid-catalyzed hot-water extraction
      process. The total fatty acid content of C. vulgaris was 296.0 mg/g cell. Under
      the 1.0% sulfuric acid, 0.4% SDBS conditions, the FFA content of the lipid
      increased to 96.7%, and the lipid-extraction yield was 248.4 mg/g cell. Under the
      2.0% sulfuric acid, 0.2% SDBS conditions, the FFA content of the lipid was 96.1%,
      and the lipid-extraction yield was 266.0mg/g cell. Whereas the FAME content of
      the microalgal lipid extracted by hexane-methanol was 76.4% at the 10.0% sulfuric
      acid concentration, the FAME content of the high-FFA microalgal lipid was
      increased to 70.1% at a sulfuric acid concentration of only 0.1%. By combined
      sulfuric acid/SDBS treatment, high-FFA microalgal lipid was extracted in large
      yields; moreover, the amount of catalyst was remarkably reduced in the
      esterification of FFA.

PMID- 24929301
TI  - Denitrifying sulfide removal and nitrososulfide complex: Azoarcus sp. NSC3 and
      Pseudomonas sp. CRS1 mix.
AB  - Denitrifying sulfide removal (DSR) process simultaneously removes nitrate,
      sulfide and organic matters in the same reactor. This study applied Azoarcus sp.
      NSC3 and Pseudomonas sp. CRS1 mix for DSR tests in autotrophic, heterotrophic and
      mixotrophic growths. Negligible NO-compounds were noted in heterotrophic or
      mixotrophic growths, while most cells were damaged and bound with NO-compounds in
      autotrophic growth. Nitroprusside (SNP) ions were applied as model compound to
      reveal the formation of nitrososulfide complex (RSNO) by nitroso (NO(+)) and
      excess sulfide (S(2-)), rather than the previously proposed mechanism by direct
      reaction between nitric oxide (NO) and S(2-). We speculated that RSNO was then
      abiotically decomposed to NO and elemental sulfur in the presence of biological
      cells. A revised nitrogen cycle considering interactions with sulfur compounds
      was proposed. We also speculated that SNO and NO were inhibitory to the
      functional strains, whose efficient removals were essential to reach high-rate
      DSR performance. 

PMID- 24929302
TI  - Volatilization and sorption of dissolved mercury by metallic iron of different
      particle sizes: implications for treatment of mercury contaminated water
      effluents.
AB  - Batch experiments were conducted to investigate the interactions between metallic
      iron particles and mercury (Hg) dissolved in aqueous solutions. The effect of
      bulk zero valent iron (ZVI) particles was tested by use of (i) granular iron and
      (ii) iron particles with diameters in the nano-size range and referred to herein
      as nZVI. The results show that the interactions between Hg(n+) and Fe(0) are
      dominated by Hg volatilization and Hg adsorption; with Hg adsorption being the
      main pathway for Hg removal from solution. Hg adsorption kinetic studies using
      ZVI and nZVI resulted in higher rate constants (k) for nZVI when k values were
      expressed as a function of mass of iron used (day(-1)g(-1)). In contrast, ZVI
      showed higher rates of Hg removal from solution when k values were expressed as a
      function iron particles' specific surface area (gm(-2)day(-1)). Overall, nZVI
      particles had a higher maximum sorption capacity for Hg than ZVI, and appeared to
      be an efficient adsorbent for Hg dissolved in aqueous solutions. 

PMID- 24929303
TI  - Development of a novel multi-functional active membrane capping barrier for the
      remediation of nitrobenzene-contaminated sediment.
AB  - A novel bio-reactive capping barrier composed of polysulfone/granular activated
      carbon (PS/GAC) hybrid membranes immobilized with microorganism was developed for
      the remediation of nitrobenzene in sediments. The SEM observation demonstrated
      that all the membranes had a dense top layer and a porous sublayer, this
      structure can block the transfer of nitrobenzene from sediment to the water and
      enhance nitrobenzene degradation. Adsorption behaviors of nitrobenzene on
      membranes showed that the membrane impregnated with GAC had better performance
      than the pure PS membrane. The values of Kads increased from 4.64 (without GAC)
      to 6.19 (1:2 GAC). 20mg/L nitrobenzene can be completely degraded by Pseudomonas
      putida immobilized on membranes. The biodegradation rate of activated carbon
      filled membrane system was little higher than that of pure PS membrane system.
      For remediation experiments, only about 21.7, 28.3 and 43.9% of nitrobenzene in
      the sediment was removed by the end of the experiments for PS/GAC membrane, sand
      alone and sand amended with activated carbon capping systems, respectively. While
      for PS/GAC+microorganisms capping system, more than 70% of nitrobenzene loss was
      observed. This demonstrated that nitrobenzene can be effectively removed from
      contaminated sediments by microbial degradation in the bio-reactive capping
      system. 

PMID- 24929304
TI  - The reductive immobilization of aqueous Se(IV) by natural pyrrhotite.
AB  - The interaction of Se(IV) with natural pyrrhotite was investigated at pH
      conditions ranging from acidic to nearly neutral. The results indicate that the
      reduction rate can be described in terms of a pseudo-first order reaction. At pH
      ~4.0 to ~5.0, the rate decreased with increasing pH. Unexpectedly, at pH ~5.0,
      the rate increased with increasing reaction time. This response was also observed
      at pH ~6.0. Two different reaction mechanisms were proposed to explain pyrrhotite
      oxidation by Se(IV). Because pyrrhotite is acid-soluble and can be attacked by
      both Fe(3+) and protons, direct reduction by the released aqueous sulfide
      dominates the reaction at low pH, whereas the cyclic oxidation of aqueous Fe(2+)
      adsorbed on pyrrhotite surfaces becomes predominant at high pH. Phosphate, which
      can be irreversibly bound to Fe(3+) intermediates even under acidic conditions,
      can significantly decrease the reaction rate by an order of magnitude at pH ~4.5.
      In contrast to the thermodynamic calculations and the predicted prevalence of
      FeSe based on previous reports of aqueous Se(IV) reduction by synthetic
      mackinawite or troilite, only Se(0) was observed as the reaction product in this
      study. This observation confirmed that a slow reaction favors the formation of
      Se(0) rather than iron selenides. 

PMID- 24929305
TI  - Radical induced degradation of acetaminophen with Fe3O4 magnetic nanoparticles as
      heterogeneous activator of peroxymonosulfate.
AB  - Magnetic nano-scaled particles Fe3O4 were studied for the activation of
      peroxymonosulfate (PMS) to generate active radicals for degradation of
      acetaminophen (APAP) in water. The Fe3O4 MNPs were found to effectively catalyze
      PMS for removal of APAP, and the reactions well followed a pseudo-first-order
      kinetics pattern (R(2)>0.95). Within 120min, approximately 75% of 10ppm APAP was
      accomplished by 0.2mM PMS in the presence of 0.8g/L Fe3O4 MNPs with little Fe(3+)
      leaching (<4MUg/L). Higher Fe3O4 MNP dose, lower initial APAP concentration,
      neutral pH, and higher reaction temperature favored the APAP degradation. The
      production of sulfate radicals and hydroxyl radicals was validated through two
      ways: (1) indirectly from the scavenging tests with scavenging agents, tert-butyl
      alcohol (TBA) and ethanol (EtOH); (2) directly from the electron paramagnetic
      resonance (ESR) tests with 0.1M 5,5-dimethyl-1-pyrrolidine N-oxide (DMPO).
      Plausible mechanisms on the radical generation from Fe3O4 MNP activation of PMS
      are proposed based on the results of radical identification tests and XPS
      analysis. It appeared that Fe(2+)Fe(3+) on the catalyst surface was responsible
      for the radical generation. The results demonstrated that Fe3O4 MNPs activated
      PMS is a promising technology for water pollution caused by contaminants such as
      pharmaceuticals. 

PMID- 24929306
TI  - Lichen Permelia perlata: a novel system for biodegradation and detoxification of
      disperse dye Solvent Red 24.
AB  - Lichen is a self-supporting symbiotic association of fungi and algae which was
      not yet explored for its bioremediation potential. Lichen Permelia perlata showed
      potential of decolorization and biodegradation of Solvent Red 24 (SR24). Optimum
      pH and temperature for decolorization was found to be 8 and 50 degrees C,
      respectively. Induction in the activity of laccase in P. perlata during
      biodegradation of SR24 showed their involvement. HPTLC, FTIR and GC-HRMS analysis
      confirmed biodegradation of SR24 in to metabolites such as naphthalen-1
      yldiazene, naphthalene, 1-(2-methylphenyl)-2-phenyldiazene and diphenyldiazene.
      Phytotoxicity and genotoxicity analysis revealed the reduction in toxicity of
      SR24 after its biodegradation. 

PMID- 24929307
TI  - How does ASD symptomology correlate with ADHD presentations?
AB  - Elevated rates of attention deficit/hyperactivity disorder (ADHD) symptoms have
      been documented in the autism spectrum disorder (ASD) population. However, the
      recent restructuring of the ASD diagnostic category and its respective symptom
      structure has elicited concern about how these changes may impact prevalence
      rates, the deliverance of services, and the rates of comorbid psychopathology. At
      present, few researchers have investigated the prevalence rates of specific ADHD
      presentations within ASD populations. As we seek to increase our understanding of
      ADHD symptom manifestation in ASD populations it is important to establish base
      rates of attention and hyperactive symptoms. The current manuscript sought to
      investigate the prevalence of inattention and impulsive symptoms in 1722 infants
      and toddlers. Individuals were separated into three diagnostic groups for
      analyses, a DSM-5 ASD group, an atypically developing group, and a DSM-IV-TR ASD
      group. Initial analysis extended previous research by demonstrating significantly
      elevated rates of inattention/impulsive symptoms in toddlers meeting DSM-5
      criteria for ASD when compared to the DSM-IV-TR ASD and atypically developing
      groups. Additional analysis demonstrated that ASD symptom severity was positively
      correlated with inattention/impulsive symptoms regardless of primary diagnosis.
      Lastly, analyses examined the exhibition of inattention and impulsive symptoms
      separately within diagnostic groups. Results suggest that the expression of
      impulsive and inattentive symptoms did not significantly differ within diagnostic
      groups. 

PMID- 24929308
TI  - The isolation and characterization of dammarenediol synthase gene from Panax
      quinquefolius and its heterologous co-expression with cytochrome P450 gene PqD12H
      in yeast.
AB  - Panax quinquefolius is one of perennial herbs and well known for its outstanding
      pharmacological activity. Ginsenosides are thought to be the main active
      ingredients in Panax quinquefolius and exist in many kinds of plant genus Panax
      (ginseng). Dammarenediol synthase, which is considered as a key enzyme in
      ginsenoside biosynthesis pathway can convert 2, 3-oxidosqualene into
      dammarenediol-II. However, the dammarenediol synthase gene in Panax quinquefolius
      has not been identified. Here, we cloned and identified a dammarenediol synthase
      gene from Panax quinquefolius (PqDS, GenBank accession No. KC316048) at the first
      time, and reverse transcription-PCR (RT-PCR) analysis also showed an obvious
      transcription increase of PqDS in the methyl jasmonate (MeJA)-induced hairy
      roots. Ectopic expression of PqDS in yeast resulted in the production of
      dammarenediol-II was confirmed by liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry (LC/APCIMS). Moreover, overexpression of
      PqDS in transgenic hairy roots could increase the transcription of gene PqDS and
      another P450 gene PqD12H (encoding protopanaxadiol synthase in Panax
      quinquefolius), the accumulation of ginsenosides also increased at the same time.
      In addition, both PqDS and PqD12H gene co-expressed in recombinant yeast result
      in the production of protopanaxadiol was detected by LC/APCIMS; this result also
      provides a new strategy for the abundant production of protopanaxadiol in vitro. 

PMID- 24929309
TI  - Production of cellobiose dehydrogenase from a newly isolated white rot fungus
      Termitomyces sp. OE147.
AB  - Class I cellobiose dehydrogenases (CDHs) are extracellular hemoflavo enzymes
      produced at low levels by the Basidiomycetes (white rot fungi). In presence of
      suitable electron acceptors, e.g., cytochrome c, 2,6-dichlorophenol-indophenol,
      or metal ions, it oxidizes cellobiose to cellobionolactone. A stringent
      requirement for disaccharides makes CDH also useful for conversion of lactose to
      lactobionic acid, an important ingredient in pharma and detergent industry. In
      this work, class I CDH was produced using a newly identified white rot fungus
      Termitomyces sp. OE147. Four media were evaluated for CDH production, and maximum
      enzyme activity of 0.92 international unit (IU)/ml was obtained on Ludwig medium
      under submerged conditions. Statistical optimization of N source, which had
      significant effect on CDH production, using Box-Behnken design followed by
      optimization of inoculum size and age resulted in an increase in activity to 2.9
      IU/ml and a productivity of ~25 IU/l/h. The nearly purified CDH exhibited high
      activity of 26.4 IU/mg protein on lactose indicating this enzyme to be useful for
      lactobionic acid synthesis. Some of the internal peptide sequences bore 100 %
      homology to the CDH produced in Myceliophthora thermophila. The fungal isolate
      was amenable to scale up, and an overall productivity of ~18 IU/l/h was obtained
      at 14-l level.

PMID- 24929310
TI  - Impedance spectroscopic characterization of Sm2O3 containing lithium borate
      glasses.
AB  - 27.5 Li2O-(72.5-X) B2O3-X Sm2O3 (X=0.5, 1, 1.5 and 2) were prepared by
      conventional melt quench technique. Impedance spectroscopy (IS) is used to study
      the electrical properties of these prepared glasses. Modulus formalism is
      introduced to study relaxation behaviour of these glasses. Scaling model shows
      the good overlap of data on single master curve which suggests that conduction
      mechanism in these glasses is compositional dependent. Variation of dielectric
      constant and dielectric loss with the addition of Sm2O3 and frequency are
      discussed here. 

PMID- 24929311
TI  - Vibrational spectroscopy of the sulphate mineral sturmanite from Kuruman
      manganese deposits, South Africa.
AB  - The mineral sturmanite is a hydrated calcium iron aluminium manganese sulphate
      tetrahydroxoborate hydroxide of formula Ca6(Fe, Al,
      Mn)2(SO4)2(B(OH)4)(OH)12.26H2O. We have studied the mineral sturmanite using a
      number of techniques, including SEM with EPMA and vibrational spectroscopy.
      Chemical analysis shows a homogeneous phase, composed by Ca, Fe, Mn, S, Al and
      Si. B is not determined in this EPMA technique. An intense Raman band at 990cm(
      1) is assigned to the SO4(2-) symmetric stretching mode. Raman spectroscopy
      identifies multiple sulphate symmetric stretching modes in line with the three
      sulphate crystallographically different sites. Raman spectroscopy also identifies
      a band at 1069cm(-1) which may be attributed to a carbonate symmetric stretching
      mode, indicating the presence of thaumasite. Infrared spectra display two bands
      at 1080 and 1107cm(-1) assigned to the SO4(2-) antisymmetric stretching modes.
      The observation of multiple bands in this nu4 spectral region offers evidence for
      the reduction in symmetry of the sulphate anion from Td to C2v or even lower
      symmetry. The Raman band at 3622cm(-1) is assigned to the OH unit stretching
      vibration and the broad feature at around 3479cm(-1) to water stretching bands.
      Infrared spectroscopy shows a set of broad overlapping bands in the OH stretching
      region. Vibrational spectroscopy enables an assessment of the molecular structure
      of sturmanite to be made. 

PMID- 24929312
TI  - Naked-eye detection of biologically important anions by a new chromogenic azo
      azomethine sensor.
AB  - A new chromogenic azo-azomethine sensor, containing active phenolic sites, has
      been designed and synthesized via condensation reaction of N,N,N',N'-tetrakis(2
      aminoethyl)-2,2-dimethyl propane-1,3-diamine with 1-(3-formyl-4-hydroxyphenylazo)
      4-nitrobenzene. The anion recognition ability of the synthesized receptor was
      evaluated using UV-Vis spectroscopy and (1)H NMR technique. The anion recognition
      studies exhibited that the receptor acts as a sensor for biologically important
      anions such as F(-), AcO(-) and H2PO4(-) over other anions. The binding
      stoichiometry between sensor and anions was found to be 1:2. (1)H NMR experiment
      revealed that sensor recognizes anions via H-bonds and subsequent deprotonation
      to elicit a vivid color change. Interestingly, the sensory system not only let
      for the naked eye detection without any spectroscopic instrumentation but also
      helped to discriminate between anions. 

PMID- 24929313
TI  - Fluorescent sensor for selective detection of Al(3+) based on quinoline-coumarin
      conjugate.
AB  - A fluorescence probe, 8-formyl-7-hydroxyl-4-methyl coumarin - (2'-methylquinoline
      4-formyl) hydrazone (L) has been synthesized. The chemosensor is found
      preferential binding to Al(3+) in presence of other competitive ions with
      associated changes in its optical and fluorescence spectra behavior. Upon
      addition of Al(3+) to a solution of L, it shows 200-fold enhancement of
      fluorescence intensity which might be attributed to form a 2:1 stoichiometry of
      the binding mode of LAl(III) and the chelation enhanced fluorescence (CHEF)
      process at 479nm in ethanol. The lowest detection limit for Al(3+) is determined
      as 8.2*10(-7)M. 

PMID- 24929314
TI  - ESIPT inspired dual fluorescent probe (Z)-3-((4-(4-aminobenzyl) phenyl) amino)
      1,3-diphenylprop-2-en-1-one: experimental and DFT based approach to photophysical
      properties.
AB  - A fluorescent probe (Z)-3-((4-(4-aminobenzyl) phenyl) amino)-1,3-diphenylprop-2
      en-1-one (L) was synthesized and characterized by IR, (1)H NMR, ESI mass, UV
      visible and fluorescence spectroscopy and by single crystal X-ray diffraction.
      The molecule has a stable helical structure due to intermolecular CH pi
      interaction. The thermal stability of L was studied by TG analysis. The
      electronic structure calculations of L have been carried out using DFT at B3LYP/6
      31G (d,p) level. The vibrational frequencies and (1)H NMR spectra were computed
      at this level and compared with experimental values. Major orbital contributions
      for the electronic transitions were assigned with the help of time-dependent
      density functional theory (TD-DFT). The observed electronic absorption spectra of
      L in different solvents coincide with the computed spectra in keto form. The dual
      emission and high Stokes shift values support the excited state intramolecular
      proton transfer (ESIPT) process. The molecular docking has been employed to get
      information about the interaction of L with DNA [6BNA]. 

PMID- 24929315
TI  - A selectively fluorescein-based colorimetric probe for detecting copper(II) ion.
AB  - A novel fluorescein derivative 3-bromo-5-methylsalicylaldehyde fluorescein
      hydrazone (BMSFH) has been synthesized by reacting fluorescein hydrazide with 3
      bromo-5-methylsalicylaldehyde and was developed as a new colorimetric probe for
      detection of Cu(2+). In the presence of Cu(2+) the BMSFH exhibits a rapid color
      change from colorless to yellow together with an obvious new band appeared at
      502nm in the UV-vis absorption spectra. However, other common alkali-, alkaline
      earth-, transition- and rare earth metal ions induced no or minimal spectral
      changes. This change is attributed to BMSFH via coordination with Cu(2+) in a 1:1
      stoichiometry and this binding to Cu(2+) is reversible, as indicated by the
      bleaching of the color when the Cu(2+) is extracted with EDTA. Experimental
      results indicate that the BMSFH can provide a rapid, selective and sensitive
      response to Cu(2+) with a linear dynamic range 3.0-330MUmol/L and can be used as
      a potential Cu(2+) colorimetric probe in aqueous solution. 

PMID- 24929316
TI  - Synthesis, characterization and dielectric properties of SnO2 thin films.
AB  - SnO2 thin films have been grown on glass substrates using Successive Ionic Layer
      Adsorption and Reaction (SILAR) method at room temperature and ambient pressure.
      The annealing temperature effect on the structural, morphological, optical and
      electrical properties of SnO2 thin films has been investigated. The X-ray
      Diffraction (XRD) and Scanning Electron Microscopy (SEM) studies have showed that
      all the films have exhibited polycrystalline nature with tetragonal structure and
      have been covered well on glass substrates. The crystalline and surface
      properties of the films have improved with increasing annealing temperature. The
      band gap values have been changed from 3.73 to 3.66eV depending on the annealing
      temperature. The refractive index (n), optical static and high frequency
      dielectric constants (epsilono, epsiloninfinity) values have been calculated as a
      function of the annealing temperature. The resistivity values of the films have
      changed between 10(-1) - 10(-3)Omegacm with annealing temperature and light at
      room temperature. 

PMID- 24929317
TI  - Quantum dots (QDs) based fluorescence probe for the sensitive determination of
      kaempferol.
AB  - In this work, using the quenching of fluorescence of thioglycollic acid (TGA)
      capped CdTe quantum dots (QDs), a novel method for the determination of
      kaempferol (KAE) has been developed. Under optimum conditions, a linear
      calibration plot of the quenched fluorescence intensity at 552nm against the
      concentration of KAE was observed in the range of 4-44MUgmL(-1) with a detection
      limit (3sigma/K) of 0.79MUgmL(-1). In addition, the detailed reaction mechanism
      has also been proposed on the basis of electron transfer supported by ultraviolet
      visible (UV-vis) absorption and fluorescence (FL) spectroscopy. The method has
      been applied for the determination of KAE in pharmaceutical preparations with
      satisfactory results. The proposed method manifested several advantages such as
      high sensitivity, short analysis time, low cost and ease of operation. 

PMID- 24929318
TI  - N-phenyl-1-naphthylamine/beta-cyclodextrin inclusion complex as a new fluorescent
      probe for rapid and visual detection of Pd(2+).
AB  - Inclusion complex between N-phenyl-1-naphthylamine (NPN) and beta-cyclodextrin
      (beta-CD) was studied by FT-IR, (1)H and 2D NMR, XRD, FT-Raman, SEM and DSC
      techniques. The formation of 1:1 stoichiometric inclusion complex of NPN with
      beta-CD was proposed based on the Nuclear magnetic resonance spectroscopy and
      Molecular docking study. The molecular encapsulation of host-guest inclusion
      complex based on simple chemosensor has high selectivity and sensitivity for the
      determination of Pd(2+) ion. Host-guest inclusion complex as a spectroscopic
      probe is used for the detection of transition metal cation Pd(2+). Coordination
      of this Pd(2+) with (NPN/beta-CD) inclusion complex exhibited a noticeable color
      change in the solution state it used for naked-eye detection. 

PMID- 24929319
TI  - Photoinduced interaction studies on N-(2-methylthiophenyl)-2-hydroxy-1
      naphthadiamine with TiO2 nanoparticles: a combined experimental and theoretical
      (DFT and spectroscopic) approach.
AB  - Schiff base derivative synthesized by the reaction of 2-(methylthio) aniline and
      2-hydroxy-1-naphthaldehyde exhibits keto-amine tautomerism in methanol solvent.
      The fluorescence quenching of N-(2-methyl thiophenyl)-2-hydroxy-1-naphthadiamine
      (NMTHN) by TiO2 nanoparticles in methanol has been studied. The excitation and
      emission peaks have been observed at 439 and 509nm respectively. The apparent
      association constant has been deduced from the absorption spectral changes of
      NMTHN-TiO2 nanoparticles using Bensi-Hildebrand equation. The number of binding
      sites and the binding constant have been calculated from the relevant
      fluorescence data. Quenching of fluorescence of NMTHN by TiO2 could be due to a
      dynamic mode. Density Functional Theory (DFT) calculations also have been
      performed to study the charge distribution of NMTHN-TiO2 both in ground and
      excited states. The HOMO-LUMO analysis of NMTHN-TiO2 in the ground state has been
      made. 

PMID- 24929320
TI  - Application of response surface methodology for determination of methyl red in
      water samples by spectrophotometry method.
AB  - In this study a rapid and effective method (dispersive liquid-liquid
      microextraction (DLLME)) was developed for extraction of methyl red (MR) prior to
      its determination by UV-Vis spectrophotometry. Influence variables on DLLME such
      as volume of chloroform (as extractant solvent) and methanol (as dispersive
      solvent), pH and ionic strength and extraction time were investigated. Then
      significant variables were optimized by using a Box-Behnken design (BBD) and
      desirability function (DF). The optimized conditions (100MUL of chloroform, 1.3mL
      of ethanol, pH 4 and 4% (w/v) NaCl) resulted in a linear calibration graph in the
      range of 0.015-10.0mgmL(-1) of MR in initial solution with R(2)=0.995 (n=5). The
      limits of detection (LOD) and limit of quantification (LOQ) were 0.005 and
      0.015mgmL(-1), respectively. Finally, the DLLME method was applied for
      determination of MR in different water samples with relative standard deviation
      (RSD) less than 5% (n=5). 

PMID- 24929321
TI  - A combined experimental and theoretical investigation of a new imineoxime and its
      palladium(II) and platinum(II) complexes: synthesis, structural characterization
      and spectroscopic properties.
AB  - A new imineoxime compound {(1E,2E)-(2-hydroxy-ethylimino)-naphthalene-2yl-ethanal
      oxime (heineoH)} and its palladium(II) and platinum(II) complexes ([M(heineo)2])
      have been synthesized and characterized by IR, NMR, UV-vis, elemental analysis,
      mass spectra and X-ray single crystal diffraction. [Pt(heineo)2] was obtained as
      a single crystal, while [Pd(heineo)2] was synthesized as a polycrystalline
      powder. The X-ray diffraction analysis of the [Pt(heineo)2] indicated that the
      platinum(II) ion is coordinated by two heineo ligands in a distorted square
      planar geometry. DFT (B3LYP/6-311++G(d,p) and LANL2DZ) calculations on the ligand
      and its complexes were carried out to correlate the geometry and vibrational and
      electronic properties. Additionally, heineoH is fluorescent in EtOH at room
      temperature, but the fluorescence is quenched in the case of the metal complexes.

PMID- 24929322
TI  - Determination of acetylsalicylic acid in commercial tablets by SERS using silver
      nanoparticle-coated filter paper.
AB  - In this work, filter paper was used as a low cost substrate for silver
      nanoparticles in order to perform the detection and quantification of
      acetylsalicylic acid by SERS in a commercial tablet. The reaction conditions were
      150mM of ammonium hydroxide, 50mM of silver nitrate, 500mM of glucose, 12min of
      the reaction time, 45 degrees C temperature, pretreatment with ammonium hydroxide
      and quantitative filter paper (1-2MUm). The average size of silver nanoparticles
      deposited on the paper substrate was 180nm. Adsorption time of acetylsalicylic
      acid on the surface of the silver-coated filter paper was studied and an
      adsorption time of 80min was used to build the analytical curve. It was possible
      to obtain a calibration curve with good precision with a coefficient of
      determination of 0.933. The method proposed in this work was capable to quantify
      acetylsalicylic acid in commercial tablets, at low concentration levels, with
      relative error of 2.06% compared to the HPLC. The preparation of filter paper
      coated with silver nanoparticles using Tollen's reagent presents several
      advantages such as low cost of synthesis, support and reagents; minimum amount of
      residuals, which are easily treated, despite the SERS spectroscopy presenting
      fast analysis, with low sample preparation and low amount of reactants as in HPLC
      analysis. 

PMID- 24929323
TI  - Spectroscopic characterization of recently excavated archaeological potsherds
      from Tamilnadu, India with multi-analytical approach.
AB  - A combined analytical study of potsherds excavated from different archaeological
      sites of Tamilnadu (Kavalapatti, Nattapuraki and Thamaraikulam villages), India
      are analyzed by spectroscopic techniques such as FTIR, X-ray diffraction,
      thermogravimetric analysis (TGA) and Scanning Electron Microscope (SEM) coupled
      with Energy Dispersive Spectrometer (EDS). FTIR and XRD techniques have been
      attempted to characterize the mineralogical composition, firing temperature and
      firing conditions of the archaeological potsherds. Thermogravimetric analysis
      (TGA) is the complementary study to estimate the firing temperature from
      characteristic thermal reactions in potsherds under controlled firing in inert
      gas atmosphere. Further, Scanning Electron Microscopy (SEM) equipped and coupled
      with an Energy Dispersive Spectrometer (EDS) to analyze internal morphology and
      chemical composition of the potsherds was used. From the results of the above
      techniques, the firing temperatures of potsherds were found to be greater than
      650 degrees C. 

PMID- 24929324
TI  - Differential susceptibility to maternal expressed emotion in children with ADHD
      and their siblings? Investigating plasticity genes, prosocial and antisocial
      behaviour.
AB  - The differential susceptibility theory states that children differ in their
      susceptibility towards environmental experiences, partially due to plasticity
      genes. Individuals carrying specific variants in such genes will be more
      disadvantaged in negative but, conversely, more advantaged in positive
      environments. Understanding gene-environment interactions may help unravel the
      causal mechanisms involved in multifactorial psychiatric disorders such as
      Attention-Deficit/Hyperactivity Disorder (ADHD). The differential susceptibility
      theory was examined by investigating the presence of interaction effects between
      maternal expressed emotion (EE; warmth and criticism) and the solitary and
      combined effects of plasticity genes (DAT1, DRD4, 5-HTT) on prosocial and
      antisocial behaviour (measured with parent- and self-reports) in children with
      ADHD and their siblings (N = 366, M = 17.11 years, 74.9% male). Maternal warmth
      was positively associated with prosocial behaviour and negatively with antisocial
      behaviour, while maternal criticism was positively associated with antisocial
      behaviour and negatively with prosocial behaviour. No evidence of differential
      susceptibility was found. The current study found no evidence for differential
      susceptibility based on the selected plasticity genes, in spite of strong EE
      behaviour associations. It is likely that additional factors play a role in the
      complex relationship between genes, environment and behaviour.

PMID- 24929325
TI  - Germline mutations of TP53 gene in breast cancer.
AB  - Germline alterations of the TP53 gene encoding the p53 protein have been observed
      in the majority of families with the Li-Fraumeni syndrome, a rare dominantly
      inherited disorder with breast cancer. Genomic DNA samples of 182 breast cancer
      cases and 186 controls were sequenced for TP53 mutations in the exon 5-9 and
      intervening introns 5, 7-9. Direct sequencing was done using Applied Biosystem
      3730 DNA analyzer. In the present study, we observed nine mutations in the
      sequenced region, of which five were novel. Hardy-Weinberg equilibrium (HWE) was
      done for all the mutations; C14181T, T14201G, and G13203A have shown deviation
      from HWE. High linkage disequilibrium (LD) was observed between C14181T
      (rs129547788) and T14201G (rs12951053) (r (2) = 0.98.3; D' = 1.00), whereas other
      observed mutations do not show strong LD with any of the other mutations. None of
      the intronic mutations has shown significant association with the breast cancer,
      two exonic mutations G13203A (rs28934578) and A14572G are significantly (P =
      0.04, P = 0.007) associated with breast cancer. Germline mutations observed in
      DNA-binding domain of the gene showed significant association with breast cancer.
      This study reports five novel germline mutations in the TP53 gene out of which
      one mutation may confer significant risk to the breast cancer. Mutations in DNA
      binding domain of TP53 gene may play role in the early onset and prognosis of
      breast cancer. The population-based studies of germline mutations in DNA-binding
      domain of TP53 gene helps in identification of individuals and families who are
      at risk of developing cancers.

PMID- 24929326
TI  - Aberrant promoter methylation of the SFRP1 gene may contribute to colorectal
      carcinogenesis: a meta-analysis.
AB  - This meta-analysis of published cohort studies was conducted to evaluate whether
      promoter methylation of the secreted frizzled-related protein 1 (SFRP1) gene
      contributes to colorectal carcinogenesis. The Web of Science (1945 ~ 2013), the
      Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~
      2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~
      2013) were searched without language restrictions. Meta-analysis was conducted
      using the STATA 12.0 software. We calculated odds ratio (OR) and its 95 %
      confidence interval (95 % CI) to estimate the correlations between SFRP1 promoter
      methylation and colorectal carcinogenesis. In the present meta-analysis, 8 cohort
      studies with a total of 942 patients with colorectal cancer (CRC) were included.
      The pooled results revealed that the frequency of SFRP1 promoter methylation in
      cancer tissues were significantly higher than those of normal, adjacent, and
      benign tissues (cancer tissues vs. normal tissues: OR = 31.49, 95 % CI = 17.57 ~
      56.44, P < 0.001; cancer tissues vs. adjacent tissues: OR = 5.95, 95 % CI 3.12 ~
      10.00, P < 0.001; cancer tissues vs. benign tissues: OR = 3.01, 95 % CI 1.72 ~
      5.27, P < 0.001; respectively). Furthermore, ethnicity-stratified analysis
      indicated that SFRP1 promoter methylation was strongly correlated with colorectal
      carcinogenesis among both Asians and Caucasians (all P < 0.05). Our findings
      provide empirical evidence that SFRP1 promoter methylation may be correlated with
      the pathogenesis of CRC.

PMID- 24929327
TI  - Association of IL-8-251A>T polymorphisms with oral cancer risk: evidences from a
      meta-analysis.
AB  - The findings of associations between interleukin-8 (IL-8) polymorphisms and risk
      of oral cancer are controversial. We conducted a meta-analysis on the basis of
      data from all published studies to provide evidence of the current understanding
      of the genetic association with oral cancer. Eligible studies were identified by
      means of an electronic search of PubMed, Elsevier, ScienceDirect, EMBASE, EBSCO,
      and CBM databases for studies published up to March 2013. In accordance with the
      inclusion and exclusion criteria, a total of six eligible studies were included
      in the pooled analyses. In the overall analysis, we did not observe any
      significant associations between the IL-8-251A>T polymorphism and oral cancer
      risk under any of the genetic models (all P > 0.05). In the stratified analysis
      by ethnicity, Caucasian individuals with genotype AA had a higher risk of oral
      cancer under the dominant model (OR = 1.35, 95 % CI 1.09-1.67, P = 0.006). This
      meta-analysis indicated that the IL-8-251A>T polymorphism was not associated with
      the susceptibility of oral cancer, while individuals in the Caucasian population
      with genotype AA had a higher risk of oral cancer under the dominant model.

PMID- 24929328
TI  - Single-nucleotide polymorphisms of LIG1 associated with risk of lung cancer.
AB  - To investigate the association of LIG1 with the risk of lung cancer, all subjects
      of unrelated ethnic Han Chinese in Liaoning Province were involved in a hospital
      based case-control study. The case group consisted of 370 histologically
      diagnosed lung cancer patients; 314 controls were selected from cancer-free
      patients during Dec. 2009 to Dec. 2011. LIG1 rs1050298SNP were analyzed by TaqMan
      real-time PCR method. All statistical analyses were performed with Statistical
      Product and Service Solution sv13.0 (SPSS). The genotype distribution frequency
      of LIG1 rs1050298 SNP displayed significant difference between the case and the
      control group. Individuals carrying the LIG1 rs1050298 T genotype had higher
      risks of lung cancer, especially those with squamous cell carcinoma.

PMID- 24929330
TI  - Clinical and neuroimaging findings in neonatal herpes simplex virus infection.
AB  - In a retrospective review of infants with neonatal herpes simplex virus disease
      (n=29), we found bilateral multilobar (n=8), pontine (n=3), thalamic (n=6), and
      internal capsule and corticospinal tract (n=5) involvement on magnetic resonance
      imaging (MRI). Diffusion-weighted imaging (n=6) performed early revealed
      additional involvement than detected by conventional MRI. Neurodevelopmental
      sequelae were correlated with MRI abnormalities. Our findings demonstrate that
      MRI, including diffusion-weighted imaging, is a valuable prognostic adjunct in
      neonatal herpes simplex virus disease.

PMID- 24929329
TI  - Role of astrocytes in thiamine deficiency.
AB  - Thiamine deficiency (TD) is the underlying cause of Wernicke's encephalopathy
      (WE), an acute neurological disorder characterized by structural damage to key
      periventricular structures in the brain. Increasing evidence suggests these focal
      histological lesions may be representative of a gliopathy in which astrocyte
      related changes are a major feature of the disorder. These changes include a loss
      of the glutamate transporters GLT-1 and GLAST concomitant with elevated
      interstitial glutamate levels, lowered brain pH associated with increased lactate
      production, decreased levels of GFAP, reduction in the levels of glutamine
      synthetase, swelling, alterations in levels of aquaporin-4, and disruption of the
      blood-brain barrier. This review focusses on how these manifestations contribute
      to the pathophysiology of TD and possibly WE. 

PMID- 24929331
TI  - Hypothermia therapy for neonatal hypoxic ischemic encephalopathy in the state of
      California.
AB  - OBJECTIVE: To characterize the implementation of hypothermia for neonatal hypoxic
      ischemic encephalopathy (HIE) in a population-based cohort. STUDY DESIGN: Using
      the California Perinatal Quality Care Collaborative and California Perinatal
      Transport System linked 2010-2012 datasets, we categorized infants>=36 weeks'
      gestation with HIE as receiving hypothermia or normothermia. Sociodemographic and
      clinical factors were compared, and multivariable logistic regression was used to
      determine factors associated with hypothermia therapy. RESULTS: There were 238
      reported encephalopathy cases in 2010, 280 in 2011, and 311 in 2012. Hypothermia
      therapy use in newborns with HIE increased from 59% to 73% across the study
      period, mainly occurring in newborns with mild or moderate encephalopathy. A
      total of 36 centers provided hypothermia and cared for 94% of infants, with the
      remaining 6% being cared for at one of 25 other centers. Of the centers providing
      hypothermia, 12 centers performed hypothermia therapy to more than 20 patients
      during the 3-year study period, and 24 centers cared for <20 patients receiving
      hypothermia. In-hospital mortality was 13%, which primarily was associated with
      the severity of encephalopathy. CONCLUSIONS: Our findings highlight an
      opportunity to explore practice-site variation and to develop quality improvement
      interventions to assure consistent evidence-based care of term infants with HIE
      and appropriate application of hypothermia therapy for eligible newborns.

PMID- 24929332
TI  - Impaired range of motion of limbs and spine in chronic fatigue syndrome.
AB  - OBJECTIVE: To determine whether adolescents and young adults with chronic fatigue
      syndrome (CFS) have a greater prevalence of impaired range of motion (ROM) of the
      limbs and spine than healthy control patients. STUDY DESIGN: Case-control study
      comparing rates of abnormal ROM in 48 consecutive adolescents and young adults
      with CFS and 48 healthy control patients matched by sex and joint hypermobility.
      We examined range of ankle dorsiflexion, passive straight-leg raise, seated
      slump, upper-limb neurodynamic test, prone knee bend, and prone press-up.
      Abnormal ROM was defined before the study began. The number of abnormal responses
      ranged from 0 (normal ROM throughout) to 11 (impaired ROM in all areas tested).
      RESULTS: The median number of areas with impaired ROM was greater in patients
      with CFS at the onset of stretch in the involved limb (5 vs 2, P<.001) and at end
      range (2 vs 0, P<.001). Patients with CFS were more likely to have greater than 3
      areas of impaired ROM (OR 6.0, 95% CI 2.1-17.3; P<.001) and were more likely to
      develop abnormal symptomatic responses to the individual tests and to the overall
      assessment (40% vs 4%; P<.001). CONCLUSIONS: Impaired ROM is more common in
      subjects with CFS than in healthy adolescents and young adults matched by sex and
      joint hypermobility. Adding a longitudinal strain to the nerves and soft tissues
      provoked symptoms in some subjects with CFS. The causes, functional impact, and
      optimal treatment of these abnormalities warrant further study.

PMID- 24929333
TI  - Detection of bloodstream infections and prediction of bronchopulmonary dysplasia
      in preterm neonates with an electronic nose.
AB  - We show that smellprints of volatile organic components measured with an
      electronic nose (Cyranose 320; Smiths Detection Group Ltd, Watford, United
      Kingdom) differ between tracheal aspirates from preterm neonates with or without
      laboratory-confirmed bloodstream infections and with or without subsequent
      development of bronchopulmonary dysplasia. Tracheal aspirate smellprints could be
      useful noninvasive diagnostic markers for preterm neonates. 

PMID- 24929334
TI  - There is something in the ear: mondini dysplasia.

PMID- 24929335
TI  - Cause of death among infants in rural western China: a community-based study
      using verbal autopsy.
AB  - OBJECTIVES: To determine the causes of death among infants in high-mortality
      areas of western China with the use of globally recognized methods. STUDY DESIGN:
      A survey of all infant deaths identified over 1 year in 4 counties in Yunnan and
      Xinjiang in which combined verbal autopsy was combined with a physician's
      diagnosis of the cause to calculate the local infant mortality rate. RESULTS:
      Among 470 completed investigations, a cause of death was assigned to 423 cases
      (90%). Overall, pneumonia (34.5%), preterm birth complications (16.5%), diarrhea
      (10.4%), birth asphyxia (10.3%), and congenital abnormalities (8.5%) were the
      main causes, with 56.6% of deaths occurring in the neonatal period. Deaths were
      attributable predominantly to prematurity or birth asphyxia in the early neonatal
      period, whereas infection accounted for more than 60% and 80% of deaths in the
      late and postneonatal periods, respectively. Calculated infant mortality was 21.9
      in 1000 live births. CONCLUSIONS: The pattern of infant mortality observed in the
      surveyed counties differs markedly from that reported previously at the national
      level, with a high proportion the result of causes that may be preventable with
      globally recommended interventions. Financial and political support is needed to
      promote improved cause of death surveillance and newborn and infant health care
      in China's western region.

PMID- 24929336
TI  - Coarse-grained analysis of stochastically simulated cell populations with a
      positive feedback genetic network architecture.
AB  - Among the different computational approaches modelling the dynamics of isogenic
      cell populations, discrete stochastic models can describe with sufficient
      accuracy the evolution of small size populations. However, for a systematic and
      efficient study of their long-time behaviour over a wide range of parameter
      values, the performance of solely direct temporal simulations requires
      significantly high computational time. In addition, when the dynamics of the cell
      populations exhibit non-trivial bistable behaviour, such an analysis becomes a
      prohibitive task, since a large ensemble of initial states need to be tested for
      the quest of possibly co-existing steady state solutions. In this work, we study
      cell populations which carry the lac operon network exhibiting solution
      multiplicity over a wide range of extracellular conditions (inducer
      concentration). By adopting ideas from the so-called "equation-free" methodology,
      we perform systems-level analysis, which includes numerical tasks such as the
      computation of coarse steady state solutions, coarse bifurcation analysis, as
      well as coarse stability analysis. Dynamically stable and unstable macroscopic
      (population level) steady state solutions are computed by means of bifurcation
      analysis utilising short bursts of fine-scale simulations, and the range of
      bistability is determined for different sizes of cell populations. The results
      are compared with the deterministic cell population balance model, which is valid
      for large populations, and we demonstrate the increased effect of stochasticity
      in small size populations with asymmetric partitioning mechanisms. 

PMID- 24929337
TI  - Is more better? Higher sterilization of infected hosts need not result in reduced
      pest population size.
AB  - We analyze the effect of sterilization in the infected hosts in several
      epidemiological models involving infectious diseases that can be transmitted both
      vertically and horizontally. Sterilizing pathogens can be used as pest control
      agents by intentionally inoculating the target population, with the goal of
      reducing or eliminating it completely. Contrary to previous models that did not
      include vertical transmission we found that the population size at the endemic
      equilibrium may actually increase with higher levels of sterility. This effect is
      proved to exist for low to high efficiencies of vertical transmission. On the
      other hand, if the disease is sexually transmitted and the host reproduction and
      disease transmission are both consistently mediated by mating, we do not observe
      such a counter-intuitive effect and the population size in the stable endemic
      equilibrium is decreasing with higher levels of sterility. We suggest that models
      of the pest control techniques involving the release of sterilizing pathogens
      have to carefully consider the routes such pathogens use for transmission. 

PMID- 24929338
TI  - E6 and E7 interactions with micro-RNA.

PMID- 24929339
TI  - Comparing lactate and glycerol as a single-electron donor for sulfate reduction
      in fluidized bed reactors.
AB  - Among the greatest challenges to the full implementation of biological sulfate
      reduction are the cost and availability of the electron source. With the
      development of the biofuel industry, new organic substrates have become
      available. Therefore, this work sought to compare the performance of a
      sulfidogenic process utilizing either lactate or glycerol as the substrate for
      sulfate-reducing bacteria (SRB) growth. Although sulfate reduction is
      energetically more favorable with lactate, glycerol is a less expensive
      alternative because excess production is forecasted with the worldwide
      development of the biodiesel industry. Continuous experiments were performed in a
      fluidized bed (FB) reactor containing activated carbon as a carrier for a mixed
      bacterial population composed of sulfate-reducing and fermentative bacteria.
      During the lactate-fed phases, incomplete oxidation of lactate to acetate by SRB
      was the dominant metabolic pathway resulting in as much as 90 % sulfate reduction
      and high acetate concentrations (2.7 g L(-1)). Conversely, in the glycerol-fed
      phases, glycerol degradation resulted from syntrophic cooperation between sulfate
      reducing and fermentative bacteria that produce butyrate along with acetate (1.0
      g L(-1)) as oxidation products. To our knowledge, this is the first report of
      butyrate formation during sulfate reduction in a glycerol-fed continuous-flow
      reactor. Sulfate concentrations were reduced by about 90 % (from 2,000 to 100-300
      mg L(-1)) when glycerol was being fed to the reactor. Since the FB reactor was
      able to stand a change from lactate to glycerol, this reactor is recommended as
      the preferred option should glycerol be selected as a cost-effective alternative
      to lactate for continuous sulfate reduction.

PMID- 24929340
TI  - Phonon waveguides for electromechanical circuits.
AB  - Nanoelectromechanical systems (NEMS), utilizing localized mechanical vibrations,
      have found application in sensors, signal processors and in the study of
      macroscopic quantum mechanics. The integration of multiple mechanical elements
      via electrical or optical means remains a challenge in the realization of NEMS
      circuits. Here, we develop a phonon waveguide using a one-dimensional array of
      suspended membranes that offers purely mechanical means to integrate isolated
      NEMS resonators. We demonstrate that the phonon waveguide can support and guide
      mechanical vibrations and that the periodic membrane arrangement also creates a
      phonon bandgap that enables control of the phonon propagation velocity.
      Furthermore, embedding a phonon cavity into the phonon waveguide allows mobile
      mechanical vibrations to be dynamically switched or transferred from the
      waveguide to the cavity, thereby illustrating the viability of waveguide
      resonator coupling. These highly functional traits of the phonon waveguide
      architecture exhibit all the components necessary to permit the realization of
      all-phononic NEMS circuits. 

PMID- 24929341
TI  - Selective transport control on molecular velcro made from intrinsically
      disordered proteins.
AB  - The selectivity and speed of many biological transport processes transpire from a
      'reduction of dimensionality' that confines diffusion to one or two dimensions
      instead of three. This behaviour remains highly sought after on polymeric
      surfaces as a means to expedite diffusional search processes in molecular
      engineered systems. Here, we have reconstituted the two-dimensional diffusion of
      colloidal particles on a molecular brush surface. The surface is composed of
      phenylalanine-glycine nucleoporins (FG Nups)--intrinsically disordered proteins
      that facilitate selective transport through nuclear pore complexes in eukaryotic
      cells. Local and ensemble-level experiments involving optical trapping using a
      photonic force microscope and particle tracking by video microscopy,
      respectively, reveal that 1-um-sized colloidal particles bearing nuclear
      transport receptors called karyopherins can exhibit behaviour that varies from
      highly localized to unhindered two-dimensional diffusion. Particle diffusivity is
      controlled by varying the amount of free karyopherins in solution, which
      modulates the multivalency of Kap-binding sites within the molecular brush. We
      conclude that the FG Nups resemble stimuli-responsive molecular 'velcro', which
      can impart 'reduction of dimensionality' as a means of biomimetic transport
      control in artificial environments.

PMID- 24929342
TI  - Conformationally constrained goniofufurone mimics as inhibitors of tumour cells
      growth: Design, synthesis and SAR study.
AB  - Synthesis of conformationally restricted (+)-goniofufurone (1) and 7-epi-(+)
      goniofufurone (2) analogues, with embedded O-isopropylidene, O-methylidene or
      cyclic carbonate functions is disclosed starting from d-glucose. A number of
      potential bioisosteres of 1 and 2 bearing both 5,7-O-methylidene and 4
      substituted cinnamoyloxy functions at the C-7 position have also been
      synthesized. In vitro cytotoxicity of target molecules against a number of human
      tumour cell lines were recorded and compared with those observed for the parent
      molecules 1 and 2. Some of the analogues displayed powerful antiproliferative
      effects on selected human tumour cell lines, but all of them were devoid of any
      cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study
      reveals the structural features of these lactones that may increase their
      antiproliferative activity.

PMID- 24929343
TI  - Microwave-assisted synthesis of C-8 aryl and heteroaryl inosines and
      determination of their inhibitory activities against Plasmodium falciparum purine
      nucleoside phosphorylase.
AB  - 8-Arylinosines have been scarcely studied for therapeutic purposes, probably due
      to difficulties in their synthesis. The recently described direct arylation
      reaction at position 8 of purine nucleosides has been employed to synthesize a
      series of 8-aryl and 8-pyridylinosines. These compounds have been studied for
      hydrolytic stability and subjected to biological evaluation. Three compounds have
      shown a pronounced specific inhibition of Plasmodium falciparum-encoded purine
      nucleoside phosphorylase, an important target for antimalarial chemotherapy. 

PMID- 24929344
TI  - Synthesis and identification of cytotoxic diphyllin glycosides as vacuolar H(+)
      ATPase inhibitors.
AB  - The concise syntheses of two natural diphyllin glycosides Cleistanthin-A (CA),
      Cleistanthoside-A (CleA) and its derivative, Cleistanthoside-A tetraacetate
      (CleT), have been achieved. They were evaluated for their in vitro anti
      proliferative activities against MCF-7, HeLa, HepG2, HCT-116, U251 cancer cell
      lines by MTT assay. Both of CA and CleT were anti-proliferative to these cancer
      cells at nanomolar concentrations. They have been shown to inhibit the activity
      of vacuolar H(+)-ATPase (V-ATPase) in HepG2 cells and neutralize the pH of
      lysosomes at nanomolar concentrations.

PMID- 24929345
TI  - Fast Gaussian kernel learning for classification tasks based on specially
      structured global optimization.
AB  - For a practical pattern classification task solved by kernel methods, the
      computing time is mainly spent on kernel learning (or training). However, the
      current kernel learning approaches are based on local optimization techniques,
      and hard to have good time performances, especially for large datasets. Thus the
      existing algorithms cannot be easily extended to large-scale tasks. In this
      paper, we present a fast Gaussian kernel learning method by solving a specially
      structured global optimization (SSGO) problem. We optimize the Gaussian kernel
      function by using the formulated kernel target alignment criterion, which is a
      difference of increasing (d.i.) functions. Through using a power-transformation
      based convexification method, the objective criterion can be represented as a
      difference of convex (d.c.) functions with a fixed power-transformation
      parameter. And the objective programming problem can then be converted to a SSGO
      problem: globally minimizing a concave function over a convex set. The SSGO
      problem is classical and has good solvability. Thus, to find the global optimal
      solution efficiently, we can adopt the improved Hoffman's outer approximation
      method, which need not repeat the searching procedure with different starting
      points to locate the best local minimum. Also, the proposed method can be proven
      to converge to the global solution for any classification task. We evaluate the
      proposed method on twenty benchmark datasets, and compare it with four other
      Gaussian kernel learning methods. Experimental results show that the proposed
      method stably achieves both good time-efficiency performance and good
      classification performance. 

PMID- 24929347
TI  - OSL and thermally assisted OSL response in dental enamel for its possible
      application in retrospective dosimetry.
AB  - Dental enamel was studied for its thermoluminescence (TL) and optically
      stimulated luminescence (OSL) defects. The TL studies showed a wide glow curve
      with multiple peaks. The thermally assisted OSL (TA-OSL) studies showed that the
      integrated TA-OSL and thus OSL signal increases with readout temperature between
      100 and 250  degrees C, due to the temperature dependence of OSL. The thermally
      assisted energy E A associated with this increase is found to be 0.21 +/- 0.015
      eV. On the other hand, the signal intensity decreases with temperature between
      260 and 450  degrees C. This decrease could be due to depletion of OSL active
      traps or possible thermal quenching. The increase of the OSL signal at increased
      temperature can be used to enhance the sensitivity of dental enamel for ex vivo
      measurements in retrospective dosimetry. The emission and excitation spectra of
      its luminescence centers were studied by photoluminescence and were found to be
      at 412 and 324 nm, respectively. It was found to possess multiple OSL active
      traps having closely lying photoionization cross sections characterized by
      continuous wave OSL and nonlinear OSL methods. The investigated dental enamel
      samples showed a linear OSL dose response up to 500 Gy. The dose threshold was
      found to be 100 mGy using a highly sensitive compact OSL reader with blue LED
      (470 nm) stimulation.

PMID- 24929346
TI  - Modification of radiation-induced oral mucositis (mouse) by adult stem cell
      therapy: single-dose irradiation.
AB  - Early oral mucositis occurs in response to accidental upper partial body exposure
      as well as to radiotherapy in the head-and-neck region. This study was initiated
      to define the potential of mobilization of endogenous bone marrow (BM) stem cells
      by rHuG-CSF or of bone marrow transplantation (BMT) to reduce the effect of
      single-dose irradiation on mouse oral epithelium. A 3 * 3 mm(2) area of the lower
      tongue surface of mice was irradiated with graded single doses (day 0). Mucosal
      ulceration was used as the endpoint for dose-response analyses. Stem cells were
      mobilized by rHuG-CSF (8 times/4 days), timed to achieve a maximum of circulating
      stem cells on days 0, +1, +4, +8 or +10. Alternatively, syngeneic BM was
      transplanted on these days. The ED(50) (dose at which ulceration is expected in
      50 % of the animals) for irradiation alone was 11.9 +/- 3.4 Gy. Mobilization of
      stem cells with a maximum of circulating stem cells on days +4, +8 or +10
      significantly increased the ED(50) to 25.5 +/- 10.1, 23.5 +/- 10.1 and 26.5 +/-
      13.0 Gy. In contrast, a maximum of circulating stem cells on day 0 or day +1 had
      no effect. BMT did not result in a significant change in isoeffective doses in
      any of the protocols. In conclusion, the response of oral mucosal epithelium to a
      single-radiation exposure can be significantly reduced by post-exposure
      mobilization, but not by transplantation, of BM stem cells.

PMID- 24929348
TI  - Temporal dynamics of bird community composition: an analysis of baseline
      conditions from long-term data.
AB  - Numerous anthropogenic activities threaten the biodiversity found on earth.
      Because all ecological communities constantly experience temporal turnover due to
      natural processes, it is important to distinguish between change due to
      anthropogenic impact and the underlying natural rate of change. In this study, we
      used data sets on breeding bird communities that covered at least 20 consecutive
      years, from a variety of terrestrial ecosystems, to address two main questions.
      (1) How fast does the composition of bird communities change over time, and can
      we identify a baseline of natural change that distinguishes primeval systems from
      systems experiencing varying degrees of human impact? (2) How do patterns of
      temporal variation in composition vary among bird communities in ecosystems with
      different anthropogenic impacts? Time lag analysis (TLA) showed a pattern of
      increasing rate of temporal compositional change from large-scale primeval
      systems to disturbed and protected systems to distinctly successional systems.
      TLA slopes of <0.04 were typical for breeding bird communities with natural
      turnover, while communities subjected to anthropogenic impact were characterised
      by TLA slopes of >0.04. Most of the temporal variability of breeding bird
      communities was explained by slow changes occurring over decades, regardless of
      the intensity of human impact. In most of the time series, medium- and short-wave
      periodicity was not detected, with the exception of breeding bird communities
      subjected to periodic pulses (e.g. caterpillar outbreaks causing food resource
      peaks). 

PMID- 24929349
TI  - Can transgenerational plasticity contribute to the invasion success of annual
      plant species?
AB  - Adaptive transgenerational plasticity (TGP), i.e., significantly higher fitness
      when maternal and offspring conditions match, might contribute to the population
      growth of non-native species in highly variable environments. However,
      comparative studies that directly test this hypothesis are lacking. Therefore, we
      performed a reciprocal split-brood experiment to compare TGP in response to N and
      water availability in single populations of two invasive (Amaranthus retroflexus,
      Galinsoga parviflora) and two congeneric non-invasive introduced species
      (Amaranthus albus, Galinsoga ciliata). We hypothesized that the transgenerational
      effect is adaptive: (1) in invasive species compared with non-invasive
      adventives, and (2) in stressful conditions compared with resource-rich
      environments. The phenotypic variation among offspring was generated, in large
      part, by our experimental treatments in the maternal generation; therefore, we
      demonstrated a direct TGP effect on the offspring's adult fitness. We found
      evidence, for the first time, that invasive and non-invasive adventive species
      differ regarding the expression of TGP in the adult stage, as adaptive responses
      were found exclusively in the invasive species. The manifestation of TGP was more
      explicit under resource-rich conditions; therefore, it might contribute to the
      population dynamics of non-native species in resource-rich sites rather than to
      their ecological tolerance spectra. 

PMID- 24929350
TI  - Use of the REG1 anticoagulation system in patients with acute coronary syndromes
      undergoing percutaneous coronary intervention: results from the phase II RADAR
      PCI study.
AB  - AIMS: We sought to determine the feasibility of conducting percutaneous coronary
      intervention (PCI) in high-risk acute coronary syndrome (ACS) patients utilising
      the REG1 system consisting of pegnivacogin, an aptameric factor IXa inhibitor,
      and its controlling agent anivamersen. METHODS AND RESULTS: In RADAR, ACS
      patients were randomised to pegnivacogin 1 mg/kg with 25%, 50%, 75%, or 100%
      anivamersen reversal or unfractionated heparin. Of the 640 patients randomised,
      388 (61%) underwent PCI. Major modified ACUITY 30-day bleeding rates were 18%
      (25% reversal), 12% (50% reversal), 9% (75% reversal), and 7% (100% reversal),
      compared with 11% with heparin. The corresponding total bleeding rates were 68%,
      39%, 35%, 34%, and 38% (heparin). Ischaemic events were less frequent in those
      receiving pegnivacogin versus heparin (4.4% vs. 7.3%, p=0.3). Thirty-day urgent
      TVR (1.1% vs. 0.9%, p=1.0), myocardial infarction (4.0% vs. 6.4%, p=0.3), and
      angiographic complication (11.2% and 10.8%, p=0.9) rates were similar with
      pegnivacogin and heparin. There were no incidences of clot formation on
      guidewires or catheters. CONCLUSIONS: High-level factor IXa inhibition in ACS
      patients undergoing PCI, with at least 50% reversal, has a favourable bleeding
      profile and appears effective at suppressing ischaemic events and thrombotic
      complications. Larger phase trials in PCI are warranted. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.gov NCT00932100.

PMID- 24929351
TI  - Atrazine reduces reproduction in Japanese medaka (Oryzias latipes).
AB  - Atrazine is an effective broadleaf herbicide and the second most heavily used
      herbicide in the United States. Effects along the hypothalamus-pituitary-gonad
      axis in a number of vertebrate taxa have been demonstrated. Seasonally elevated
      concentrations of atrazine in surface waters may adversely affect fishes, but
      only a few studies have examined reproductive effects of this chemical. The
      present study was designed to evaluate a population endpoint (egg production) in
      conjunction with histological (reproductive stage, gonad pathology) and
      biochemical (aromatase activity, sex hormone production) phenotypes associated
      with atrazine exposure in Japanese medaka. Adult virgin breeding groups of one
      male and four females were exposed to nominal concentrations of 0, 0.5, 5.0, and
      50 MUg/L (0, 2.3, 23.2, 231 nM) of atrazine in a flow-through diluter for 14 or
      38 days. Total egg production was lower (36-42%) in all atrazine-exposed groups
      as compared to the controls. The decreases in cumulative egg production of
      atrazine-treated fish were significant by exposure day 24. Reductions in total
      egg production in atrazine treatment groups were most attributable to a reduced
      number of eggs ovulated by females in atrazine-treated tanks. Additionally, males
      exposed to atrazine had a greater number of abnormal germ cells. There was no
      effect of atrazine on gonadosomatic index, aromatase protein, or whole body 17
      beta-estradiol or testosterone. Our results suggest that atrazine reduces egg
      production through alteration of final maturation of oocytes. The reduced egg
      production observed in this study was very similar to our previously reported
      results for fathead minnow. This study provides further information with which to
      evaluate atrazine's risk to fish populations.

PMID- 24929352
TI  - Effects of water accommodated fractions of crude oils and diesel on a suite of
      biomarkers in Atlantic cod (Gadus morhua).
AB  - The aim of this study was to characterize concentration- and time-dependent
      responses in juvenile Atlantic cod (Gadus morhua) following exposure for one and
      three weeks to the water-soluble fraction (WAF) of three weathered oils: Arabian
      Light crude oil (ALC), North Sea crude oil (NSC) and ship-diesel. The sum of
      polycyclic aromatic hydrocarbons (PAH) in water was highest after one week of
      exposure and within environmentally relevant concentrations. PAH metabolites in
      bile confirmed exposure to and uptake of PAHs. Hepatic cytochrome P450 1A (CYP1A)
      gene expression (mRNA quantification) increased dramatically following exposure
      to all three oil types (fold-change up to 165) and there was a time lag between
      gene and protein expression. Hepatic CYP1A protein concentration and
      ethoxyresorufin-O-deethylase (EROD) activity were more variable among individuals
      and treatments than gene expression. EROD activity in liver and gills increased
      in fish exposed to WAF from the two crude oils, but not in fish exposed to WAF
      from diesel. Exposure to diesel appeared to induce oxidative stress to a greater
      extent than exposure to crude oils. Other biomarkers (glutathione S-transferases,
      acetylcholine esterase, vitellogenin) did not appear to respond to the exposure
      and hence did not discriminate among oils. Biomarker responses in cod after
      exposure to weathered crude oils and diesel suggested that the CYP1A system and
      oxidative stress markers have the highest potential for discriminating among
      different oil types and to monitor the environmental consequences of spills. 

PMID- 24929353
TI  - Metal-PAH mixtures in the aquatic environment: a review of co-toxic mechanisms
      leading to more-than-additive outcomes.
AB  - Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) occur ubiquitously
      in aquatic environments, yet relatively little is known regarding their combined
      toxicities. Emerging reports investigating the additive mortality in metal-PAH
      mixtures have indicated that more-than-additive effects are equally as common as
      strictly-additive effects, raising concern for ecological risk assessment
      typically based on the summation of individual toxicities. Moreover, the current
      separation of focus between in vivo and in vitro studies, and fine- and coarse
      scale endpoints, creates uncertainty regarding the mechanisms of co-toxicity
      involved in more-than-additive effects on whole organisms. Drawing from
      literature on metal and PAH toxicity in bacteria, protozoa, invertebrates, fish,
      and mammalian models, this review outlines several key mechanistic interactions
      likely to promote more-than-additive toxicity in metal-PAH mixtures. Namely, the
      deleterious effects of PAHs on membrane integrity and permeability to metals, the
      potential for metal-PAH complexation, the inhibitory nature of metals to the
      detoxification of PAHs via the cytochrome P450 pathway, the inhibitory nature of
      PAHs towards the detoxification of metals via metallothionein, and the
      potentiated production of reactive oxygenated species (ROS) in certain metal
      (e.g. Cu) and PAH (e.g., phenanthrenequinone) mixtures. Moreover, the mutual
      inhibition of detoxification suggests the possibility of positive feedback among
      these mechanisms. The individual toxicities and interactive aspects of
      contaminant transport, detoxification, and the production of ROS are herein
      discussed. 

PMID- 24929354
TI  - The iceberg of suicide and self-harm in Irish adolescents: a population-based
      study.
AB  - PURPOSE: Suicide is a leading cause of death among adolescents. Self-harm is the
      most important risk factor for suicide, yet the majority of self-harm does not
      come to the attention of health services. The purpose of this study was to
      establish the relative incidence of adolescent suicide, hospital-treated self
      harm and self-harm in the community. METHODS: Annual suicide rates were
      calculated for 15-17 year-old in the Cork and Kerry region in Ireland based on
      data from the Central Statistics Office. Rates of hospital-treated self-harm were
      collected by the Irish National Registry of Deliberate Self-Harm. Rates of self
      harm in the community were assessed using a survey of 3,881 adolescents, the
      Child and Adolescent Self-harm in Europe study. RESULTS: The annual suicide rate
      was 10/100,000. Suicide was six times more common among boys than girls. The
      annual incidence rate of hospital-treated self-harm was approximately
      344/100,000, with the female rate almost twice the male rate. The rate of self
      harm in the community was 5,551/100,000, and girls were almost four times more
      likely to report self-harm. For every boy who died by suicide, 16 presented to
      hospital with self-harm and 146 reported self-harm in the community. For every
      female suicide, 162 girls presented to hospital with self-harm and 3,296 reported
      self-harm. CONCLUSIONS: Gender differences in relative rates of self-harm and
      suicide are very large, with boys who have harmed themselves at particularly high
      risk of suicide. Knowledge of the relative incidence of self-harm and suicide in
      adolescents can inform prevention programmes and services.

PMID- 24929356
TI  - An audit of cancer of unknown primary notifications: A cautionary tale for
      population health research using cancer registry data.
AB  - BACKGROUND: Cancer of unknown primary (CUP) is a common cancer yet little is
      known about the reliability of incidence data. METHODS: We audited 574 CUP
      (C80.9) diagnoses (median age 81 years) registered by the New South Wales (NSW)
      Central Cancer Registry (2004-2007) in a cohort of Australian Government
      Department of Veterans' Affairs clients. The registry did not clarify diagnoses
      with notifiers during this period due to interpretation of privacy legislation.
      For the audit, current registry practice was applied by seeking additional
      information from CUP notifiers and reclassifying diagnoses as necessary. In
      addition, clinicopathological characteristics were extracted from notifications.
      Fisher's exact test and Student's t-test were used to compare the demographic and
      clinicopathological characteristics of the CUP subgroups. Age/sex-standardised
      CUP incidence rates and 95% confidence intervals were calculated, standardised to
      the 2001 Australian population. RESULTS: 172 (30.0%) cases were reclassified to a
      known primary site, mostly cutaneous, and nine (1.6%) were found to be non
      malignant diagnoses. After the audit the age/sex-standardised CUP incidence rates
      decreased from 26.0 (95% CI 21.2-30.8) to 15.9 (95% CI 12.5-19.3) per 100,000
      person-years. Of the 393 remaining CUP cases, 202 (51%) were registered on the
      basis of a clinical diagnosis (46 by death certificate only) and 191 (49%) by
      pathological diagnosis (79 by cytology alone). Compared to cases with a
      pathological diagnosis, cases with a clinical diagnosis were older (85.6 vs. 82.0
      years, p<0.001), and the reported number and location of metastases differed
      (p<0.001); metastatic sites were more likely to be unspecified for clinical
      diagnoses (36.1% vs. 4.2%). CONCLUSIONS: Cancer registry processes can markedly
      influence CUP incidence. Future population-based CUP research should take this
      into account, and consider stratification by basis of diagnosis due to
      differences in patient and tumour characteristics.

PMID- 24929355
TI  - Frequencies and predictors of barriers to mental health service use: a
      longitudinal study of Hurricane Ike survivors.
AB  - BACKGROUND: The majority of disaster survivors suffering from psychological
      symptoms do not receive mental health services. Research on barriers to service
      use among disaster survivors is limited by a lack of longitudinal studies of
      representative samples and investigations of predictors of barriers. The purpose
      of this study was to address these limitations through analysis of a three-wave
      population-based study of Hurricane Ike survivors (N = 658). METHODS: Frequencies
      of preference, outcome expectancy, resource, and stigma barriers among
      participants with unmet mental health needs were documented and logistic
      regression using a generalized estimating equations approach explored
      predisposing (e.g., age), illness-related (e.g., posttraumatic stress) and
      enabling (e.g., insurance coverage) factors as predictors of each type of
      barrier. RESULTS: Preference barriers were most frequently cited at each wave,
      whereas stigma barriers were least frequently cited. Older age and higher
      emotional support predicted preference barriers; being a parent of a child under
      18-years old at the time of the hurricane, higher generalized anxiety, and lack
      of insurance predicted resource barriers; and higher posttraumatic stress
      predicted stigma barriers. CONCLUSIONS: These findings suggest that postdisaster
      practices targeting subpopulations most likely to have barriers to service use
      may be indicated.

PMID- 24929357
TI  - Active cigarette smoking and the risk of breast cancer: a cohort study.
AB  - BACKGROUND: Tobacco use has been implicated in the etiology of a large number of
      cancers, and there exists substantial biological plausibility that it could also
      be involved in breast carcinogenesis. Despite this, epidemiological evidence to
      date is inconsistent. The aim of this study was to investigate the role of active
      smoking and the risk of incident, invasive breast cancer using a prospective
      cohort of women from the Canadian Study of Diet, Lifestyle and Health. METHODS:
      Using a case-cohort design, an age-stratified subcohort of 3314 women was created
      from 39,532 female participants who returned completed self-administered
      lifestyle and dietary questionnaires at baseline. A total of 1096 breast cancer
      cases were identified in the entire cohort (including 141 cases from the
      subcohort) by linkage to the Canadian Cancer Registry. Cox regression models were
      used to estimate hazard ratios for the association between the different smoking
      exposures and the risk of breast cancer, using a modification for the case-cohort
      design. RESULTS: After carefully considering early-life exposures and potential
      confounders, we found no association between any smoking exposure and risk of
      breast cancer in this study (Hazard ratio=1.00, 95% confidence interval=0.87-1.17
      for ever vs never smokers). CONCLUSIONS: Although these results cannot rule out
      an association between smoking and breast cancer, they do agree with the current
      literature suggesting that, if an association does exist, it is relatively weak.

PMID- 24929358
TI  - Assessment of phenol infiltration resilience in soil media by HYDRUS-1D transport
      model for a waste discharge site.
AB  - The movement of contaminants through soil imparts a variety of geo-environmental
      problem inclusive of lithospheric pollution. Near-surface aquifers are often
      vulnerable to contamination from surface source if overlying soil possesses poor
      resilience or contaminant attenuation capacity. The prediction of contaminant
      transport through soil is urged to protect groundwater from sources of
      pollutants. Using field simulation through column experiments and mathematical
      modeling like HYDRUS-1D, assessment of soil resilience and movement of
      contaminants through the subsurface to reach aquifers can be predicted. An
      outfall site of effluents of a coke oven plant comprising of alarming
      concentration of phenol (4-12.2 mg/L) have been considered for studying
      groundwater condition and quality, in situ soil characterization, and effluent
      characterization. Hydrogeological feature suggests the presence of near-surface
      aquifers at the effluent discharge site. Analysis of groundwater of nearby
      locality reveals the phenol concentration (0.11-0.75 mg/L) exceeded the
      prescribed limit of WHO specification (0.002 mg/L). The in situ soil, used in
      column experiment, possess higher saturated hydraulic conductivity (KS  = 5.25 *
      10(-4) cm/s). The soil containing 47 % silt, 11 % clay, and 1.54% organic carbon
      content was found to be a poor absorber of phenol (24 mg/kg). The linear phenol
      adsorption isotherm model showed the best fit (R(2) = 0.977, RMSE = 1.057) to the
      test results. Column experiments revealed that the phenol removal percent and the
      length of the mass transfer zone increased with increasing bed heights. The
      overall phenol adsorption efficiency was found to be 42-49%. Breakthrough curves
      (BTCs) predicted by HYDRUS-1D model appears to be close fitting with the BTCs
      derived from the column experiments. The phenol BTC predicted by the HYDRUS-1D
      model for 1.2 m depth subsurface soil, i.e., up to the depth of groundwater in
      the study area, showed that the exhaustion point was reached within 12 days of
      elapsed time. This clearly demonstrated poor attenuation capacity of the soil to
      retard migration of phenol to the groundwater from the surface outfall site.
      Suitable liner, based on these data, may be designed to inhibit subsurface
      transport of phenol and thereby to protect precious groundwater from
      contamination.

PMID- 24929359
TI  - Coupling between endocytosis and sphingosine kinase 1 recruitment.
AB  - Genetic studies have suggested a functional link between cholesterol/sphingolipid
      metabolism and endocytic membrane traffic. Here we show that perturbing the
      cholesterol/sphingomyelin balance in the plasma membrane results in the massive
      formation of clusters of narrow endocytic tubular invaginations positive for N
      BAR proteins. These tubules are intensely positive for sphingosine kinase 1
      (SPHK1). SPHK1 is also targeted to physiologically occurring early endocytic
      intermediates, and is highly enriched in nerve terminals, which are cellular
      compartments specialized for exo/endocytosis. Membrane recruitment of SPHK1
      involves a direct, curvature-sensitive interaction with the lipid bilayer
      mediated by a hydrophobic patch on the enzyme's surface. The knockdown of SPHKs
      results in endocytic recycling defects, and a mutation that disrupts the
      hydrophobic patch of Caenorhabditis elegans SPHK fails to rescue the
      neurotransmission defects in loss-of-function mutants of this enzyme. Our studies
      support a role for sphingosine phosphorylation in endocytic membrane trafficking
      beyond the established function of sphingosine-1-phosphate in intercellular
      signalling. 

PMID- 24929360
TI  - Adherens junction treadmilling during collective migration.
AB  - Collective cell migration is essential for both physiological and pathological
      processes. Adherens junctions (AJs) maintain the integrity of the migrating cell
      group and promote cell coordination while allowing cellular rearrangements. Here,
      we show that AJs undergo a continuous treadmilling along the lateral sides of
      adjacent leading cells. The treadmilling is driven by an actin-dependent rearward
      movement of AJs and is supported by the polarized recycling of N-cadherin. N
      cadherin is mainly internalized at the cell rear and then recycled to the leading
      edge where it accumulates before being incorporated into forming AJs at the front
      of lateral cell-cell contacts. The polarized dynamics of AJs is controlled by a
      front-to-rear gradient of p120-catenin phosphorylation, which regulates polarized
      trafficking of N-cadherin. Perturbation of the GSK3-dependent phosphorylation of
      p120-catenin impacts on the stability of AJs, and the polarity and speed of
      leading cells during collective migration. 

PMID- 24929361
TI  - Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling.
AB  - Signal transduction requires the coordination of activities between different
      pathways. In mammalian cells, Raf-1 regulates the MST-LATS and MEK-ERK pathways.
      We found that a complex circuitry of competing protein interactions coordinates
      the crosstalk between the ERK and MST pathways. Combining mathematical modelling
      and experimental validation we show that competing protein interactions can cause
      steep signalling switches through phosphorylation-induced changes in binding
      affinities. These include Akt phosphorylation of MST2 and a feedback
      phosphorylation of Raf-1 Ser 259 by LATS1, which enables Raf-1 to suppress both
      MST2 and MEK signalling. Mutation of Raf-1 Ser 259 stimulates both pathways,
      simultaneously driving apoptosis and proliferation, whereas concomitant MST2
      downregulation switches signalling to cell proliferation, transformation and
      survival. Thus, competing protein interactions provide a versatile regulatory
      mechanism for signal distribution through the dynamic integration of graded
      signals into switch-like responses. 

PMID- 24929363
TI  - Nitrogen and phosphorus discharge of animal origin in the Baixo Vouga: a spatial
      data analysis.
AB  - The livestock production is a strategic and crucial activity for it fixes
      populations in rural areas, contributing to its conservation, and most
      importantly because it ensures food production. By producing meat, milk or eggs,
      this sector contributes to national food self-sufficiency. However, intensive
      livestock farming activities carry a strong pollution load on the environment,
      particularly through the emission of nitrogen (N), phosphorus (P), and greenhouse
      gases (GHG). The Baixo Vouga region in Portugal due to its climatic conditions
      and soil characteristics holds a high number of livestock production units mainly
      cattle, poultry and swine. Thus such an activity contributes to a significant
      portion of the wealth created in this region. This high potential has collided
      with the existence of environmentally sensitive areas, many of which are
      protected by European environmental regulations. This work studies the
      geographical distribution of livestock population of cattle, poultry and swine in
      the Baixo Vouga region and quantifies its impacts on the environment by
      calculating the excretion loads of N and P of these species. In the cattle and
      poultry sectors two clusters or agglomerations are identified, the first in the
      northern region and the second in the inland region. Moreover, the cattle farming
      cluster overlaps on vulnerable zones requiring specific monitoring on effluent
      treatment issues. 

PMID- 24929362
TI  - Molecular diversity of the methanotrophic bacteria communities associated with
      disused tin-mining ponds in Kampar, Perak, Malaysia.
AB  - In a previous study, notable differences of several physicochemical properties,
      as well as the community structure of ammonia oxidizing bacteria as judged by 16S
      rRNA gene analysis, were observed among several disused tin-mining ponds located
      in the town of Kampar, Malaysia. These variations were associated with the
      presence of aquatic vegetation as well as past secondary activities that occurred
      at the ponds. Here, methane oxidizing bacteria (MOB), which are direct
      participants in the nutrient cycles of aquatic environments and biological
      indicators of environmental variations, have been characterised via analysis of
      pmoA functional genes in the same environments. The MOB communities associated
      with disused tin-mining ponds that were exposed to varying secondary activities
      were examined in comparison to those in ponds that were left to nature. Comparing
      the sequence and phylogenetic analysis of the pmoA clone libraries at the
      different ponds (idle, lotus-cultivated and post-aquaculture), we found pmoA
      genes indicating the presence of type I and type II MOB at all study sites, but
      type Ib sequences affiliated with the Methylococcus/Methylocaldum lineage were
      most ubiquitous (46.7 % of clones). Based on rarefaction analysis and diversity
      indices, the disused mining pond with lotus culture was observed to harbor the
      highest richness of MOB. However, varying secondary activity or sample type did
      not show a strong variation in community patterns as compared to the ammonia
      oxidizers in our previous study.

PMID- 24929365
TI  - Communication: He-tagged vibrational spectra of the SarGlyH+ and H+(H2O)(2,3)
      ions: quantifying tag effects in cryogenic ion vibrational predissociation (CIVP)
      spectroscopy.
AB  - To assess the degree to which more perturbative, but widely used "tag" species
      (Ar, H2, Ne) affect the intrinsic band patterns of the isolated ions, we describe
      the extension of mass-selective, cryogenic ion vibrational spectroscopy to the
      very weakly interacting helium complexes of three archetypal ions: the dipeptide
      SarGlyH(+) and the small protonated water clusters: H(+)(H2O)(2,3), including the
      H5O2(+) "Zundel" ion. He adducts were generated in a 4.5 K octopole ion trap
      interfaced to a double-focusing, tandem time-of-flight photofragmentation mass
      spectrometer to record mass-selected vibrational predissociation spectra. The H2
      tag-induced shift (relative to that by He) on the tag-bound NH stretch of the
      SarGlyH(+) spectrum is quite small (12 cm(-1)), while the effect on the floppy
      H5O2(+) ion is more dramatic (125 cm(-1)) in going from Ar (or H2) to Ne. The
      shifts from Ne to He, on the other hand, while quantitatively significant
      (maximum of 10 cm(-1)), display the same basic H5O2(+) band structure, indicating
      that the He-tagged H5O2(+) spectrum accurately represents the delocalized nature
      of the vibrational zero-point level. Interestingly, the He-tagged spectrum of
      H(+)(H2O)3 reveals the location of the non-bonded OH group on the central H3O(+)
      ion to fall between the collective non-bonded OH stretches on the flanking water
      molecules in a position typically associated with a neutral OH group.

PMID- 24929364
TI  - (1)H, (13)C, and (15)N backbone and sidechain chemical shift assignments for the
      HEAT2 domain of human eIF4GI.
AB  - The translation initiation factor eIF4G is required for the translation of many
      eukaryotic messenger RNAs. Its interaction with the ATP-dependent RNA helicase
      eIF4A plays an important role in the regulation of translation initiation. eIF4G
      in humans and other higher eukaryotes contains three HEAT domains, of which HEAT1
      and HEAT2 contain binding sites for eIF4A. Here we report the near complete NMR
      resonance assignment of the 192-residue HEAT2 domain of the human translation
      initiation factor eIF4GI. The chemical shift data constitute the basis for NMR
      structural studies aimed at expanding understanding of the role of interactions
      between the initiation factor eIF4A and eIF4G in translation initiation. 

PMID- 24929366
TI  - Communication: Chemical functionality of interfacial water enveloping nanoscale
      structural defects in proteins.
AB  - Building upon a non-Debye multiscale treatment of water dielectrics, this work
      reveals the biochemical role of interfacial water enveloping nanoscale structural
      defects in soluble proteins, asserting its role as a chemical base. This quasi
      reactant status is already implied by the significant concentration of structural
      defects in the vicinity of an enzymatically active site, delineating their role
      as promoters or enhancers of catalytic activity. 

PMID- 24929367
TI  - Communication: Remarkable electrophilicity of the oxalic acid monomer: an anion
      photoelectron spectroscopy and theoretical study.
AB  - Our experimental and computational results demonstrate an unusual
      electrophilicity of oxalic acid, the simplest dicarboxylic acid. The monomer is
      characterized by an adiabatic electron affinity and electron vertical detachment
      energy of 0.72 and 1.08 eV (+/-0.05 eV), respectively. The electrophilicity
      results primarily from the bonding carbon-carbon interaction in the singly
      occupied molecular orbital of the anion, but it is further enhanced by
      intramolecular hydrogen bonds. The well-resolved structure in the photoelectron
      spectrum is reproduced theoretically, based on Franck-Condon factors for the
      vibronic anion -> neutral transitions. 

PMID- 24929368
TI  - Exponential time differencing methods with Chebyshev collocation for polymers
      confined by interacting surfaces.
AB  - We present a fast and accurate numerical method for the self-consistent field
      theory calculations of confined polymer systems. It introduces an exponential
      time differencing method (ETDRK4) based on Chebyshev collocation, which exhibits
      fourth-order accuracy in temporal domain and spectral accuracy in spatial domain,
      to solve the modified diffusion equations. Similar to the approach proposed by
      Hur et al. [Macromolecules 45, 2905 (2012)], non-periodic boundary conditions are
      adopted to model the confining walls with or without preferential interactions
      with polymer species, avoiding the use of surface field terms and the mask
      technique in a conventional approach. The performance of ETDRK4 is examined in
      comparison with the operator splitting methods with either Fourier collocation or
      Chebyshev collocation. Numerical experiments show that our exponential time
      differencing method is more efficient than the operator splitting methods in high
      accuracy calculations. This method has been applied to diblock copolymers
      confined by two parallel flat surfaces. 

PMID- 24929369
TI  - Asymptotic solution of the diffusion equation in slender impermeable tubes of
      revolution. I. The leading-term approximation.
AB  - The anisotropic 3D equation describing the pointlike particles diffusion in
      slender impermeable tubes of revolution with cross section smoothly depending on
      the longitudinal coordinate is the object of our study. We use singular
      perturbations approach to find the rigorous asymptotic expression for the local
      particles concentration as an expansion in the ratio of the characteristic
      transversal and longitudinal diffusion relaxation times. The corresponding
      leading-term approximation is a generalization of well-known Fick-Jacobs
      approximation. This result allowed us to delineate the conditions on temporal and
      spatial scales under which the Fick-Jacobs approximation is valid. A striking
      analogy between solution of our problem and the method of inner-outer expansions
      for low Knudsen numbers gas kinetic theory is established. With the aid of this
      analogy we clarify the physical and mathematical meaning of the obtained results.

PMID- 24929370
TI  - Identifying the Hamiltonian structure in linear response theory.
AB  - We present a unifying framework for linear response eigenvalue equations that
      encompasses both variational Hartree-Fock and Kohn-Sham density functional theory
      as well as non-variational coupled-cluster theory. The joint description is
      rooted in the so-called Hamiltonian structure of the response kernel matrices,
      whose properties permit an immediate identification of the well-known paired
      eigenvalue spectrum describing a molecule in the isolated state. Recognizing the
      Hamiltonian structure underlying the equations further enables a generalization
      to the case of a polarizable-embedded molecule treated in variational and, in
      particular, in non-variational theories. 

PMID- 24929372
TI  - Temporal cross-correlation asymmetry and departure from equilibrium in a bistable
      chemical system.
AB  - This paper aims at determining sustained reaction fluxes in a nonlinear chemical
      system driven in a nonequilibrium steady state. The method relies on the
      computation of cross-correlation functions for the internal fluctuations of
      chemical species concentrations. By employing Langevin-type equations, we derive
      approximate analytical formulas for the cross-correlation functions associated
      with nonlinear dynamics. Kinetic Monte Carlo simulations of the chemical master
      equation are performed in order to check the validity of the Langevin equations
      for a bistable chemical system. The two approaches are found in excellent
      agreement, except for critical parameter values where the bifurcation between
      monostability and bistability occurs. From the theoretical point of view, the
      results imply that the behavior of cross-correlation functions cannot be
      exploited to measure sustained reaction fluxes in a specific nonlinear system
      without the prior knowledge of the associated chemical mechanism and the rate
      constants. 

PMID- 24929371
TI  - Derivation of coarse-grained potentials via multistate iterative Boltzmann
      inversion.
AB  - In this work, an extension is proposed to the standard iterative Boltzmann
      inversion (IBI) method used to derive coarse-grained potentials. It is shown that
      the inclusion of target data from multiple states yields a less state-dependent
      potential, and is thus better suited to simulate systems over a range of
      thermodynamic states than the standard IBI method. The inclusion of target data
      from multiple states forces the algorithm to sample regions of potential phase
      space that match the radial distribution function at multiple state points, thus
      producing a derived potential that is more representative of the underlying
      interactions. It is shown that the algorithm is able to converge to the true
      potential for a system where the underlying potential is known. It is also shown
      that potentials derived via the proposed method better predict the behavior of n
      alkane chains than those derived via the standard IBI method. Additionally,
      through the examination of alkane monolayers, it is shown that the relative
      weight given to each state in the fitting procedure can impact bulk system
      properties, allowing the potentials to be further tuned in order to match the
      properties of reference atomistic and/or experimental systems. 

PMID- 24929373
TI  - Identifiability analysis of rotational diffusion tensor and electronic transition
      moments measured in time-resolved fluorescence depolarization experiment.
AB  - The subject of this paper is studies of the deterministic identifiability of
      molecular parameters, such as rotational diffusion tensor components and
      orientation of electronic transition moments, resulting from the time-resolved
      fluorescence anisotropy experiment. In the most general case considered, a pair
      of perpendicularly polarized emissions enables the unique determination of all
      the rotational diffusion tensor's principal components. The influence of the
      tensor's symmetry and the associated degeneration of its eigenvalues on the
      identifiability of the electronic transitions moments is systematically
      investigated. The analysis reveals that independently of the rotational diffusion
      tensor's symmetry, the transition moments involved in photoselection and emission
      processes cannot be uniquely identified without a priori information about their
      mutual orientation or their orientation with respect to the principal axes of the
      tensor. Moreover, it is shown that increasing the symmetry of the rotational
      diffusion tensor deteriorates the degree of the transition moments
      identifiability. To obtain these results analytically, a novel approach to solve
      bilinear system of equations for Markov parameters is applied. The effect of the
      additional information, obtained from fluorescence measurements for different
      molecular mobilities, to improve the identifiability at various levels of
      analysis is shown. The effectiveness and reliability of the target analysis
      method for experimental determination of the molecular parameters is also
      discussed. 

PMID- 24929374
TI  - Path integral Liouville dynamics for thermal equilibrium systems.
AB  - We show a new imaginary time path integral based method--path integral Liouville
      dynamics (PILD), which can be derived from the equilibrium Liouville dynamics [J.
      Liu and W. H. Miller, J. Chem. Phys. 134, 104101 (2011)] in the Wigner phase
      space. Numerical tests of PILD with the simple (white noise) Langevin thermostat
      have been made for two strongly anharmonic model problems. Since implementation
      of PILD does not request any specific form of the potential energy surface, the
      results suggest that PILD offers a potentially useful approach for general
      condensed phase molecular systems to have the two important properties: conserves
      the quantum canonical distribution and recovers exact thermal correlation
      functions (of even nonlinear operators, i.e., nonlinear functions of position or
      momentum operators) in the classical, high temperature, and harmonic limits.

PMID- 24929375
TI  - Landau-Zener type surface hopping algorithms.
AB  - A class of surface hopping algorithms is studied comparing two recent Landau
      Zener (LZ) formulas for the probability of nonadiabatic transitions. One of the
      formulas requires a diabatic representation of the potential matrix while the
      other one depends only on the adiabatic potential energy surfaces. For each
      classical trajectory, the nonadiabatic transitions take place only when the
      surface gap attains a local minimum. Numerical experiments are performed with
      deterministically branching trajectories and with probabilistic surface hopping.
      The deterministic and the probabilistic approach confirm the affinity of both the
      LZ probabilities, as well as the good approximation of the reference solution
      computed by solving the Schrodinger equation via a grid based pseudo-spectral
      method. Visualizations of position expectations and superimposed surface hopping
      trajectories with reference position densities illustrate the effective dynamics
      of the investigated algorithms. 

PMID- 24929376
TI  - Full-dimensional diabatic potential energy surfaces including dissociation: the
      2E" state of NO3.
AB  - A scheme to produce accurate full-dimensional coupled diabatic potential energy
      surfaces including dissociative regions and suitable for dynamical calculations
      is proposed. The scheme is successfully applied to model the two-sheeted surface
      of the (2)E" state of the NO3 radical. An accurate potential energy surface for
      the NO3- anion ground state is developed as well. Both surfaces are based on high
      level ab initio calculations. The model consists of a diabatic potential matrix,
      which is expanded to higher order in terms of symmetry polynomials of symmetry
      coordinates. The choice of coordinates is key for the accuracy of the obtained
      potential energy surfaces and is discussed in detail. A second central aspect is
      the generation of reference data to fit the expansion coefficients of the model
      for which a stochastic approach is proposed. A third ingredient is a new and
      simple scheme to handle problematic regions of the potential energy surfaces,
      resulting from the massive undersampling by the reference data unavoidable for
      high-dimensional problems. The final analytical diabatic surfaces are used to
      compute the lowest vibrational levels of NO3- and the photo-electron detachment
      spectrum of NO3- leading to the neutral radical in the (2)E" state by full
      dimensional multi-surface wave-packet propagation for NO3 performed using the
      Multi-Configuration Time Dependent Hartree method. The achieved agreement of the
      simulations with available experimental data demonstrates the power of the
      proposed scheme and the high quality of the obtained potential energy surfaces.

PMID- 24929377
TI  - Two-state theory of binned photon statistics for a large class of waiting time
      distributions and its application to quantum dot blinking.
AB  - A theoretical method is proposed for the calculation of the photon counting
      probability distribution during a bin time. Two-state fluorescence and steady
      excitation are assumed. A key feature is a kinetic scheme that allows for an
      extensive class of stochastic waiting time distribution functions, including
      power laws, expanded as a sum of weighted decaying exponentials. The solution is
      analytic in certain conditions, and an exact and simple expression is found for
      the integral contribution of "bright" and "dark" states. As an application for
      power law kinetics, theoretical results are compared with experimental intensity
      histograms from a number of blinking CdSe/ZnS quantum dots. The histograms are
      consistent with distributions of intensity states around a "bright" and a "dark"
      maximum. A gap of states is also revealed in the more-or-less flat inter-peak
      region. The slope and to some extent the flatness of the inter-peak feature are
      found to be sensitive to the power-law exponents. Possible models consistent with
      these findings are discussed, such as the combination of multiple charging and
      fluctuating non-radiative channels or the multiple recombination center model. A
      fitting of the latter to experiment provides constraints on the interaction
      parameter between the recombination centers. Further extensions and applications
      of the photon counting theory are also discussed. 

PMID- 24929379
TI  - Cholesky-decomposed density MP2 with density fitting: accurate MP2 and double
      hybrid DFT energies for large systems.
AB  - Our recently developed QQR-type integral screening is introduced in our Cholesky
      decomposed pseudo-densities Moller-Plesset perturbation theory of second order
      (CDD-MP2) method. We use the resolution-of-the-identity (RI) approximation in
      combination with efficient integral transformations employing sparse matrix
      multiplications. The RI-CDD-MP2 method shows an asymptotic cubic scaling behavior
      with system size and a small prefactor that results in an early crossover to
      conventional methods for both small and large basis sets. We also explore the use
      of local fitting approximations which allow to further reduce the scaling
      behavior for very large systems. The reliability of our method is demonstrated on
      test sets for interaction and reaction energies of medium sized systems and on a
      diverse selection from our own benchmark set for total energies of larger
      systems. Timings on DNA systems show that fast calculations for systems with more
      than 500 atoms are feasible using a single processor core. Parallelization
      extends the range of accessible system sizes on one computing node with multiple
      cores to more than 1000 atoms in a double-zeta basis and more than 500 atoms in a
      triple-zeta basis. 

PMID- 24929380
TI  - Analytical solution of the Poisson-Nernst-Planck equations for an electrochemical
      system close to electroneutrality.
AB  - Single charge densities and the potential are used to describe models of
      electrochemical systems. These quantities can be calculated by solving a system
      of time dependent nonlinear coupled partial differential equations, the Poisson
      Nernst-Planck equations. Assuming small deviations from the electroneutral
      equilibrium, the linearized and decoupled equations are solved for a radial
      symmetric geometry, which represents the interface between a cell and a sensor
      device. The densities and the potential are expressed by Fourier-Bessels series.
      The system considered has a ratio between the Debye-length and its geometric
      dimension on the order of 10(-4) so the Fourier-Bessel series can be approximated
      by elementary functions. The time development of the system is characterized by
      two time constants, tau(c) and tau(g). The constant tau(c) describes the approach
      to the stationary state of the total charge and the potential. tau(c) is several
      orders of magnitude smaller than the geometry-dependent constant tau(g), which is
      on the order of 10 ms characterizing the transition to the stationary state of
      the single ion densities.

PMID- 24929378
TI  - Assessment of amide I spectroscopic maps for a gas-phase peptide using IR-UV
      double-resonance spectroscopy and density functional theory calculations.
AB  - The spectroscopy of amide I vibrations has become a powerful tool for exploring
      protein structure and dynamics. To help with spectral interpretation, it is often
      useful to perform molecular dynamics (MD) simulations. To connect spectroscopic
      experiments to simulations in an efficient manner, several researchers have
      proposed "maps," which relate observables in classical MD simulations to quantum
      spectroscopic variables. It can be difficult to discern whether errors in the
      theoretical results (compared to experiment) arise from inaccuracies in the MD
      trajectories or in the maps themselves. In this work, we evaluate spectroscopic
      maps independently from MD simulations by comparing experimental and theoretical
      spectra for a single conformation of the alpha-helical model peptide Ac-Phe
      (Ala)5-Lys-H(+) in the gas phase. Conformation-specific experimental spectra are
      obtained for the unlabeled peptide and for several singly and doubly (13)C
      labeled variants using infrared-ultraviolet double-resonance spectroscopy, and
      these spectra are found to be well-modeled by density functional theory (DFT)
      calculations at the B3LYP/6-31G** level. We then compare DFT results for the
      deuterated and (13)C(18)O-labeled peptide with those from spectroscopic maps
      developed and used previously by the Skinner group. We find that the maps are
      typically accurate to within a few cm(-1) for both frequencies and couplings,
      having larger errors only for the frequencies of terminal amides. 

PMID- 24929381
TI  - Certification and the potential energy landscape.
AB  - Typically, there is no guarantee that a numerical approximation obtained using
      standard nonlinear equation solvers is indeed an actual solution, meaning that it
      lies in the quadratic convergence basin. Instead, it may lie only in the linear
      convergence basin, or even in a chaotic region, and hence not converge to the
      corresponding stationary point when further optimization is attempted. In some
      cases, these non-solutions could be misleading. Proving that a numerical
      approximation will quadratically converge to a stationary point is termed
      certification. In this report, we provide details of how Smale's alpha-theory can
      be used to certify numerically obtained stationary points of a potential energy
      landscape, providing a mathematical proof that the numerical approximation does
      indeed correspond to an actual stationary point, independent of the precision
      employed. 

PMID- 24929382
TI  - Exchange interaction between the triplet exciton and the localized spin in copper
      phthalocyanine.
AB  - Triplet excitonic state in the organic molecule may arise from a singlet
      excitation and the following inter-system crossing. Especially for a spin-bearing
      molecule, an exchange interaction between the triplet exciton and the original
      spin on the molecule can be expected. In this paper, such exchange interaction in
      copper-phthalocyanine (CuPc, spin-1/2) was investigated from first-principles by
      using density-functional theory within a variety of approximations to the
      exchange correlation, ranging from local-density approximation to long-range
      corrected hybrid-exchange functional. The magnitude of the computed exchange
      interaction is in the order of meV with the minimum value (1.5 meV,
      ferromagnetic) given by the long-range corrected hybrid-exchange functional CAM
      B3LYP. This exchange interaction can therefore give rise to a spin coherence with
      an oscillation period in the order of picoseconds, which is much shorter than the
      triplet lifetime in CuPc (typically tens of nanoseconds). This implies that it
      might be possible to manipulate the localized spin on Cu experimentally using
      optical excitation and inter-system crossing well before the triplet state
      disappears.

PMID- 24929383
TI  - Rotational excitation of HCN by para- and ortho-H2.
AB  - Rotational excitation of the hydrogen cyanide (HCN) molecule by collisions with
      para-H2(j = 0, 2) and ortho-H2(j = 1) is investigated at low temperatures using a
      quantum time independent approach. Both molecules are treated as rigid rotors.
      The scattering calculations are based on a highly correlated ab initio 4
      dimensional (4D) potential energy surface recently published. Rotationally
      inelastic cross sections among the 13 first rotational levels of HCN were
      obtained using a pure quantum close coupling approach for total energies up to
      1200 cm(-1). The corresponding thermal rate coefficients were computed for
      temperatures ranging from 5 to 100 K. The HCN rate coefficients are strongly
      dependent on the rotational level of the H2 molecule. In particular, the rate
      coefficients for collisions with para-H2(j = 0) are significantly lower than
      those for collisions with ortho-H2(j = 1) and para-H2(j = 2). Propensity rules in
      favor of even Deltaj transitions were found for HCN in collisions with para-H2(j
      = 0) whereas propensity rules in favor of odd Deltaj transitions were found for
      HCN in collisions with H2(j ? 1). The new rate coefficients were compared with
      previously published HCN-para-H2(j = 0) rate coefficients. Significant
      differences were found due the inclusion of the H2 rotational structure in the
      scattering calculations. These new rate coefficients will be crucial to improve
      the estimation of the HCN abundance in the interstellar medium.

PMID- 24929384
TI  - Dipole polarizability of alkali-metal (Na, K, Rb)-alkaline-earth-metal (Ca, Sr)
      polar molecules: prospects for alignment.
AB  - Electronic open-shell ground-state properties of selected alkali-metal-alkaline
      earth-metal polar molecules are investigated. We determine potential energy
      curves of the (2)Sigma(+) ground state at the coupled-cluster singles and doubles
      with partial triples (CCSD(T)) level of electron correlation. Calculated
      spectroscopic constants for the isotopes ((23)Na, (39)K, (85)Rb)-((40)Ca, (88)Sr)
      are compared with available theoretical and experimental results. The variation
      of the permanent dipole moment (PDM), average dipole polarizability, and
      polarizability anisotropy with internuclear distance is determined using finite
      field perturbation theory at the CCSD(T) level. Owing to moderate PDM (KCa: 1.67
      D, RbCa: 1.75 D, KSr: 1.27 D, RbSr: 1.41 D) and large polarizability anisotropy
      (KCa: 566 a.u., RbCa: 604 a.u., KSr: 574 a.u., RbSr: 615 a.u.), KCa, RbCa, KSr,
      and RbSr are potential candidates for alignment and orientation in combined
      intense laser and external static electric fields. 

PMID- 24929385
TI  - Accuracy of the centrifugal sudden approximation in the H + CHD3 -> H2 + CD3
      reaction.
AB  - The initial state selected time-dependent wave packet method has been extended to
      calculate the coupled-channel reaction probabilities with total angular momentum
      J(tot) > 0 for the title reaction with seven degrees of freedom included. Fully
      converged integral cross sections were obtained for the ground and a number of
      vibrational excited initial states on a new potential energy surface recently
      constructed by this group using neural network fitting. As found from a previous
      study with the centrifugal sudden (CS) approximation, all these initial
      vibrational excitations investigated in this study enhance the reactivity
      considerably at a given collision energy, in particular the CH stretch excited
      state. The energy initially deposited in CH stretch motion is more effective than
      translational energy on promoting the reaction in the entire energy region, while
      for CH bending or CD3 umbrella excitations only at the high collision energy the
      vibrational energy becomes more effective. Our calculations also revealed that
      the accuracy of the CS approximation considerably deteriorates with the increase
      of J(tot), in particular on the threshold energy. The CS approximation
      underestimates the integral cross sections for all these initial states, albeit
      not very severely. In general, it works better at high collision energies and for
      vibrationally excited initial states, with the increase of integral cross
      section.

PMID- 24929386
TI  - Ab initio calculation of ICD widths in photoexcited HeNe.
AB  - Excitation of HeNe by synchrotron light just below the frequency of the 1s -> 3p
      transition of isolated He has been recently shown to be followed by resonant
      interatomic Coulombic decay (ICD). The vibrationally resolved widths of the ICD
      states were extracted with high precision from the photoion spectra. In this
      paper, we report the results of ab initio calculations of these widths. We show
      that interaction between electronic states at about the equilibrium distance of
      HeNe makes dark states of He accessible for the photoexcitation and subsequent
      electronic decay. Moreover, the values of the calculated widths are shown to be
      strongly sensitive to the presence of the non-adiabatic coupling between the
      electronic states participating in the decay. Therefore, only by considering the
      complete manifold of interacting decaying electronic states a good agreement
      between the measured and computed ICD widths can be achieved. 

PMID- 24929387
TI  - Absolute fragmentation cross sections in atom-molecule collisions: scaling laws
      for non-statistical fragmentation of polycyclic aromatic hydrocarbon molecules.
AB  - We present scaling laws for absolute cross sections for non-statistical
      fragmentation in collisions between Polycyclic Aromatic Hydrocarbons (PAH/PAH(+))
      and hydrogen or helium atoms with kinetic energies ranging from 50 eV to 10 keV.
      Further, we calculate the total fragmentation cross sections (including
      statistical fragmentation) for 110 eV PAH/PAH(+) + He collisions, and show that
      they compare well with experimental results. We demonstrate that non-statistical
      fragmentation becomes dominant for large PAHs and that it yields highly reactive
      fragments forming strong covalent bonds with atoms (H and N) and molecules
      (C6H5). Thus nonstatistical fragmentation may be an effective initial step in the
      formation of, e.g., Polycyclic Aromatic Nitrogen Heterocycles (PANHs). This
      relates to recent discussions on the evolution of PAHNs in space and the
      reactivities of defect graphene structures. 

PMID- 24929388
TI  - Threshold ionization, structural isomers, and electronic states of M2O2 (M = Sc,
      Y, and La).
AB  - M2O2 (M = Sc, Y, and La) were synthesized in a pulsed laser-vaporization
      molecular beam source and studied by mass-analyzed threshold ionization (MATI)
      spectroscopy and ab initio calculations. Adiabatic ionization energies (AIEs) and
      several vibrational frequencies were measured accurately for the first time from
      the MATI spectra. Six possible structural isomers of M2O2 were considered in the
      calculations and the three converged structures were used in the spectral
      analysis. A planar cyclic structure in D2h point group was predicted to be the
      most stable one by the theory and observed by the experiment. The cyclic
      structure is formed by joining two MO2 fragments together through two shared
      oxygen atoms. In forming the ground state clusters, each metal atom loses two (n 
      1)d electrons and as a result, has only one ns electron in the metal-based
      valence orbital. The ground electronic state of Sc2O2 is (1)A(g), and those of
      Y2O2 and La2O2 are (3)B(1u). Ionization of both (1)A(g) and (3)B(1u) neutral
      states yields the (2)A(g) ion state by removing one of the two ns electrons, and
      the resultant ion has a similar geometry to the neutral cluster. The AIEs of the
      clusters are 5.5752 (6), 5.2639 (6), 4.5795 (6) eV for M = Sc, Y, and La,
      respectively. The vibrational frequencies of the observed modes, including O-M
      and M-M stretches, are in the range of 200-800 cm(-1).

PMID- 24929389
TI  - The electric dipole moment of magnesium deuteride, MgD.
AB  - The (0,0) A(2)Pi-X (2)Sigma(+) band of a cold molecular beam sample of magnesium
      monodeuteride, MgD, has been recorded field-free and in the presence of a static
      electric field of up to 11 kV/cm. The lines associated with the lowest rotational
      levels are detected for the first time. The field-free spectrum was analyzed to
      produce an improved set of fine structure parameters for the A(2)Pi (v = 0)
      state. The observed electric field induced splittings and shifts were analyzed to
      produce permanent electric dipole moments, MU(el) of 2.567(10)D and 1.31(8)D for
      A(2)Pi (v = 0) and X(2)Sigma(+)(v = 0) states, respectively. The recommended
      value for MU(el)(X(2)Sigma(+) (v = 0)) for MgH, based upon the measured value for
      MgD, is 1.32(8)D.

PMID- 24929390
TI  - Kinetics of ion-ion mutual neutralization: halide anions with polyatomic cations.
AB  - The binary mutual neutralization (MN) of a series of 17 cations (O2+, NO(+),
      NO2+, CO(+), CO2+, Cl(+), Cl2+, SO2+, CF3+, C2F5+, NH3+, H3+, D3+, H2O(+),
      H3O(+), ArH(+), ArD(+)) with 3 halide anions (Cl(-), Br(-), I(-)) has been
      investigated in a flowing afterglow-Langmuir probe apparatus using the variable
      electron and neutral density attachment mass spectrometry technique. The MN rate
      constants of atom-atom reactions are dominated by the chemical nature of the
      system (i.e., the specific locations of curve crossings). As the number of atoms
      in the system increases, the MN rate constants become dominated instead by the
      physical nature of the system (e.g., the relative velocity of the reactants). For
      systems involving 4 or more atoms, the 300 K MN rate constants are well described
      by 2.7 * 10(-7) MU(-0.5), where the reduced mass is in Da and the resulting rate
      constants in cm(3) s(-1). An upper limit to the MN rate constants appears well
      described by the complex potential model described by Hickman assuming a cross
      section to neutralization of 11,000 A(2) at 300 K, equivalent to 3.5 * 10(-7) MU(
      0.5).

PMID- 24929391
TI  - Photoisomerization among ring-open merocyanines. I. Reaction dynamics and wave
      packet oscillations induced by tunable femtosecond pulses.
AB  - Upon ultraviolet excitation, photochromic spiropyran compounds can be converted
      by a ring-opening reaction into merocyanine molecules, which in turn can form
      several isomers differing by cis and trans configurations in the methine bridge.
      Whereas the spiropyran-merocyanine conversion reaction of the nitro-substituted
      indolinobenzopyran 6-nitro-1',3',3'-trimethylspiro[2H-1-benzopyran-2,2'-indoline]
      (6-nitro BIPS) has been studied extensively in theory and experiments, little is
      known about photoisomerization among the merocyanine isomers. In this article, we
      employ femtosecond transient absorption spectroscopy with variable excitation
      wavelengths to investigate the excited-state dynamics of the merocyanine in
      acetonitrile at room temperature, where exclusively the trans-trans-cis (TTC) and
      trans-trans-trans (TTT) isomers contribute. No photochemical ring-closure
      pathways exist for the two isomers. Instead, we found that (18+/-4)% of excited
      TTC isomers undergo an ultrafast excited-state cis->trans photoisomerization to
      TTT within 200 fs, while the excited-state lifetime of TTC molecules that do not
      isomerize is 35 ps. No photoisomerization was detected for the TTT isomer, which
      relaxes to the ground state with a lifetime of roughly 160 ps. Moreover, signal
      oscillations at 170 cm(-1) and 360 cm(-1) were observed, which can be ascribed to
      excited-state wave-packet dynamics occurring in the course of the TTC->TTT
      isomerization. The results of high-level time-dependent density functional theory
      in conjunction with polarizable continuum models are presented in the subsequent
      article [C. Walter, S. Ruetzel, M. Diekmann, P. Nuernberger, T. Brixner, and B.
      Engels, J. Chem. Phys. 140, 224311 (2014)]. 

PMID- 24929392
TI  - Photoisomerization among ring-open merocyanines. II. A computational study.
AB  - The photochemical isomerization of the trans-trans-cis to the trans-trans-trans
      isomer of the merocyanine form of 6-nitro BIPS, which has been studied with
      femtosecond transient absorption spectroscopy [S. Ruetzel, M. Diekmann, P.
      Nuernberger, C. Walter, B. Engels, and T. Brixner, J. Chem. Phys. 140, 224310
      (2014)], is investigated using time-dependent density functional theory in
      conjunction with polarizable continuum models. Benchmark calculations against SCS
      ADC(2) evaluate the applicability of the CAM-B3LYP functional. Apart from a
      relaxed scan in the ground state with additional computation of the corresponding
      excitation energies, which produces the excited-state surface vertical to the
      ground-state isomerization coordinate, a relaxed scan in the S1 gives insight
      into the geometric changes orthogonal to the reaction coordinate and the
      fluorescence conditions. The shape of the potential energy surface (PES) along
      the reaction coordinate is found to be highly sensitive to solvation effects,
      with the method of solvation (linear response vs. state-specific) being critical.
      The shape of the PES as well as the computed harmonic frequencies in the S1
      minima are in line with the experimental results and offer a straightforward
      interpretation. 

PMID- 24929393
TI  - Hylleraas-configuration-interaction nonrelativistic energies for the 1S ground
      states of the beryllium isoelectronic sequence.
AB  - In a previous work, Sims and Hagstrom ["Hylleraas-configuration-interaction study
      of the 1 (1)S ground state of neutral beryllium," Phys. Rev. A 83, 032518 (2011)]
      reported Hylleraas-configuration-interaction (Hy-CI) method variational
      calculations for the (1)S ground state of neutral beryllium with an estimated
      accuracy of a tenth of a microhartree. In this work, the calculations have been
      extended to higher accuracy and, by simple scaling of the orbital exponents, to
      the entire Be 2 (1)S isoelectronic sequence. The best nonrelativistic energies
      for Be, B(+), and C(++) obtained are -14.6673 5649 269, -24.3488 8446 36, and 
      36.5348 5236 25 hartree, respectively. Except for Be, all computed
      nonrelativistic energies are superior to the known reference energies for these
      states. 

PMID- 24929394
TI  - A nine-dimensional ab initio global potential energy surface for the H2O+ + H2 ->
      H3O+ + H reaction.
AB  - An accurate full-dimensional global potential energy surface (PES) is developed
      for the title reaction. While the long-range interactions in the reactant
      asymptote are represented by an analytical expression, the interaction region of
      the PES is fit to more than 81,000 of ab initio points at the UCCSD(T)-F12b/AVTZ
      level using the permutation invariant polynomial neural network approach. Fully
      symmetric with respect to permutation of all four hydrogen atoms, the PES
      provides a faithful representation of the ab initio points, with a root mean
      square error of 1.8 meV or 15 cm(-1). The reaction path for this exoergic
      reaction features an attractive and barrierless entrance channel, a submerged
      saddle point, a shallow H4O(+) well, and a barrierless exit channel. The rate
      coefficients for the title reaction and kinetic isotope effect have been
      determined on this PES using quasi-classical trajectories, and they are in good
      agreement with available experimental data. It is further shown that the H2O(+)
      rotational enhancement of reactivity observed experimentally can be traced to the
      submerged saddle point. Using our recently proposed Sudden Vector Projection
      model, we demonstrate that a rotational degree of freedom of the H2O(+) reactant
      is strongly coupled with the reaction coordinate at this saddle point, thus
      unraveling the origin of the pronounced mode specificity in this reaction.

PMID- 24929395
TI  - Low valency in lanthanides: a theoretical study of NdF and LuF.
AB  - The ground and low-lying excited state potential energy curves of neodymium
      monofluoride were calculated using multireference (CASSCF) and single reference
      (EOM-CR-CCSD(T)) methods. Optimized bond lengths were obtained and accurate bond
      dissociation energies were computed. The EOM-CR-CCSD(T) method was used to
      determine the bond dissociation energy of lutetium monofluoride, and it is shown
      that core correlation is required to produce bond dissociation energies in
      agreement with experiment. 

PMID- 24929396
TI  - High-resolution photoelectron imaging of cold C60- anions and accurate
      determination of the electron affinity of C60.
AB  - High-resolution photoelectron imaging and spectroscopy of cold C60- anions are
      reported using a newly built photoelectron imaging apparatus coupled with an
      electrospray ionization source and a temperature-controlled cryogenic ion trap.
      Vibrationally resolved photoelectron spectra are obtained for the detachment
      transition from the ground state of C60- to that of C60 at various detachment
      wavelengths from 354.84 nm to 461.35 nm. The electron affinity of C60 is
      accurately measured to be 2.6835 +/- 0.0006 eV. Numerous unexpected vibrational
      excitations are observed in the photoelectron spectra due to the Jahn-Teller
      effect in C60- and Hertzberg-Teller vibronic coupling in both C60- and C60. Both
      the relative intensities of vibrational peaks and their photoelectron angular
      distributions provide evidence for the vibronic couplings. The observed p-wave
      like behavior in the angular distribution of the 000 transition suggests that the
      electron is detached from an s-type orbital.

PMID- 24929397
TI  - A fixed-node diffusion Monte Carlo study of the 1,2,3-tridehydrobenzene
      triradical.
AB  - The electronic structure of 1,2,3-tridehydrobenzene was investigated using
      quantum Monte Carlo methods. The radical contains two low-lying electronic states
      that are nearly degenerate adiabatically (within 2 kcal/mol separation),
      according to previous coupled cluster calculations. We performed Diffusion Monte
      Carlo (DMC) calculations starting from Multi-Reference Configuration Interaction
      (MRCI) trial wavefunctions, with a complete active space (CAS) containing 9
      electrons in 9 orbitals, CAS(9,9). Our converged DMC results are in close
      agreement with the best coupled-cluster results, and further strengthen the
      assignment of a (2)A1 ground state. 

PMID- 24929399
TI  - The structure of D2O-nonane nanodroplets.
AB  - We study the internal structure of nanometer-sized D2O-nonane aerosol droplets
      formed in supersonic nozzle expansions using a variety of experimental techniques
      including small angle X-ray scattering (SAXS). By fitting the SAXS spectra to a
      wide range of droplet structure models, we find that the experimental results are
      inconsistent with mixed droplets that form aqueous core-organic shell structures,
      but are quite consistent with spherically asymmetric lens-on-sphere structures.
      The structure that agrees best with the SAXS data and Fourier transform infra-red
      spectroscopy measurements is that of a nonane lens on a sphere of D2O with a
      contact angle in the range of 40 degrees -120 degrees . 

PMID- 24929398
TI  - Vibrational states of a water molecule in a nano-cavity of beryl crystal lattice.
AB  - Low-energy excitations of a single water molecule are studied when confined
      within a nano-size cavity formed by the ionic crystal lattice. Optical spectra
      are measured of manganese doped beryl single crystal Mn:Be3Al2Si6O18, that
      contains water molecules individually isolated in 0.51 nm diameter voids within
      the crystal lattice. Two types of orientation are distinguished: water-I
      molecules have their dipole moments aligned perpendicular to the c axis and
      dipole moments of water-II molecules are parallel to the c-axis. The optical
      conductivity sigma(nu) and permittivity E'(nu) spectra are recorded in terahertz
      and infrared ranges, at frequencies from several wavenumbers up to nu = 7000 cm(
      1), at temperatures 5-300 K and for two polarizations, when the electric vector E
      of the radiation is parallel and perpendicular to the c-axis. Comparative
      experiments on as-grown and on dehydrated samples allow to identify the spectra
      of sigma(nu) and E'(nu) caused exclusively by water molecules. In the infrared
      range, well-known internal modes nu1, nu2, and nu3 of the H2O molecule are
      observed for both polarizations, indicating the presence of water-I and water-II
      molecules in the crystal. Spectra recorded below 1000 cm(-1) reveal a rich set of
      highly anisotropic features in the low-energy response of H2O molecule in a
      crystalline nano-cavity. While for E?c only two absorption peaks are detected, at
      ~90 cm(-1) and ~160 cm(-1), several absorption bands are discovered for E?c, each
      consisting of narrower resonances. The bands are assigned to librational (400-500
      cm(-1)) and translational (150-200 cm(-1)) vibrations of water-I molecule that is
      weakly coupled to the nano-cavity "walls." A model is presented that explains the
      "fine structure" of the bands by a splitting of the energy levels due to quantum
      tunneling between the minima in a six-well potential relief felt by a molecule
      within the cavity.

PMID- 24929400
TI  - Photochemistry of glycolaldehyde in cryogenic matrices.
AB  - The photochemistry of glycolaldehyde (GA) upon irradiation at 266 nm is
      investigated in argon, nitrogen, neon, and para-hydrogen matrices by IR
      spectroscopy. Isomerization and fragmentation processes are found to compete. The
      hydrogen-bonded Cis-Cis form of GA is transformed mainly to the open Trans-Trans
      conformer and to CO and CH3OH fragments and their mixed complexes. Different
      photo-induced behaviours appear depending on the matrix. In nitrogen, small
      amounts of Trans-Gauche and Trans-Trans conformers are detected after deposition
      and grow together upon irradiation. The Trans-Gauche conformer is characterized
      for the first time. In para-hydrogen due to a weaker cage effect additional H2CO
      and HCO fragments are seen. Calculations of the potential energy surfaces of S0,
      S1, and T1 states--to analyse the torsional deformations which are involved in
      the isomerization process--and a kinetic analysis are presented to investigate
      the different relaxation pathways of GA. Fragmentation of GA under UV irradiation
      through the CO+CH3OH molecular channel is a minor process, as in the gas phase.

PMID- 24929401
TI  - Multi-scale study of condensation in water jets using ellipsoidal-statistical
      Bhatnagar-Gross-Krook and molecular dynamics modeling.
AB  - Homogeneous water condensation and ice formation in supersonic expansions to
      vacuum for stagnation pressures from 12 to 1000 mbar are studied using the
      particle-based Ellipsoidal-Statistical Bhatnagar-Gross-Krook (ES-BGK) method. We
      find that when condensation starts to occur, at a stagnation pressure of 96 mbar,
      the increase in the degree of condensation causes an increase in the rotational
      temperature due to the latent heat of vaporization. The simulated rotational
      temperature profiles along the plume expansion agree well with measurements
      confirming the kinetic homogeneous condensation models and the method of
      simulation. Comparisons of the simulated gas and cluster number densities,
      cluster size for different stagnation pressures along the plume centerline were
      made and it is found that the cluster size increase linearly with respect to
      stagnation pressure, consistent with classical nucleation theory. The sensitivity
      of our results to cluster nucleation model and latent heat values based on bulk
      water, specific cluster size, or bulk ice are examined. In particular, the ES-BGK
      simulations are found to be too coarse-grained to provide information on the
      phase or structure of the clusters formed. For this reason, molecular dynamics
      simulations of water condensation in a one-dimensional free expansion to simulate
      the conditions in the core of a plume are performed. We find that the internal
      structure of the clusters formed depends on the stagnation temperature. A larger
      cluster of average size 21 was tracked down the expansion, and a calculation of
      its average internal temperature as well as a comparison of its radial
      distribution functions (RDFs) with values measured for solid amorphous ice
      clusters lead us to conclude that this cluster is in a solid-like rather than
      liquid form. In another molecular-dynamics simulation at a much lower stagnation
      temperature, a larger cluster of size 324 and internal temperature 200 K was
      extracted from an expansion plume and equilibrated to determine its RDF and self
      diffusion coefficient. The value of the latter shows that this cluster is formed
      in a supercooled liquid state rather than in an amorphous solid state. 

PMID- 24929402
TI  - Search for a liquid-liquid critical point in models of silica.
AB  - Previous research has indicated the possible existence of a liquid-liquid
      critical point (LLCP) in models of silica at high pressure. To clarify this
      interesting question we run extended molecular dynamics simulations of two
      different silica models (WAC and BKS) and perform a detailed analysis of the
      liquid at temperatures much lower than those previously simulated. We find no
      LLCP in either model within the accessible temperature range, although it is
      closely approached in the case of the WAC potential near 4000 K and 5 GPa.
      Comparing our results with those obtained for other tetrahedral liquids, and
      relating the average Si-O-Si bond angle and liquid density at the model glass
      temperature to those of the ice-like beta-cristobalite structure, we conclude
      that the absence of a critical point can be attributed to insufficient
      "stiffness" in the bond angle. We hypothesize that a modification of the
      potential to mildly favor larger average bond angles will generate a LLCP in a
      temperature range that is accessible to simulation. The tendency to crystallize
      in these models is extremely weak in the pressure range studied, although this
      tendency will undoubtedly increase with increasing stiffness. 

PMID- 24929403
TI  - Potential energy landscape of the two-dimensional XY model: higher-index
      stationary points.
AB  - The application of numerical techniques to the study of energy landscapes of
      large systems relies on sufficient sampling of the stationary points. Since the
      number of stationary points is believed to grow exponentially with system size,
      we can only sample a small fraction. We investigate the interplay between this
      restricted sample size and the physical features of the potential energy
      landscape for the two-dimensional XY model in the absence of disorder with up to
      N = 100 spins. Using an eigenvector-following technique, we numerically compute
      stationary points with a given Hessian index I for all possible values of I. We
      investigate the number of stationary points, their energy and index
      distributions, and other related quantities, with particular focus on the scaling
      with N. The results are used to test a number of conjectures and approximate
      analytic results for the general properties of energy landscapes. 

PMID- 24929404
TI  - Local vibrational dynamics of hematite (alpha-Fe2O3) studied by extended x-ray
      absorption fine structure and molecular dynamics.
AB  - The local vibrational dynamics of hematite (alpha-Fe2O3) has been investigated by
      temperature-dependent extended x-ray absorption fine structure spectroscopy and
      molecular dynamics simulations. The local dynamics of both the short and long
      nearest-neighbor Fe-O distances has been singled out, i.e., their local thermal
      expansion and the parallel and perpendicular mean-square relative atomic
      displacements have been determined, obtaining a partial agreement with molecular
      dynamics. No evidence of the Morin transition has been observed. More
      importantly, the strong anisotropy of relative thermal vibrations found for the
      short Fe-O distance has been related to its negative thermal expansion. The
      differences between the local dynamics of short and long Fe-O distances are
      discussed in terms of projection and correlation of atomic motion. As a result,
      we can conclude that the short Fe-O bond is stiffer to stretching and softer to
      bending than the long Fe-O bond. 

PMID- 24929405
TI  - Distribution of diffusion constants and Stokes-Einstein violation in supercooled
      liquids.
AB  - It is widely believed that the breakdown of the Stokes-Einstein (SE) relation
      between the translational diffusivity and the shear viscosity in supercooled
      liquids is due to the development of dynamic heterogeneity, i.e., the presence of
      both slow and fast moving particles in the system. In this study we directly
      calculate the distribution of the diffusivity for a model system for different
      temperatures in the supercooled regime. We find that with decreasing temperature,
      the distribution evolves from Gaussian to bimodal indicating that on the time
      scale of the typical relaxation time, mobile (fluid like) and less mobile (solid
      like) particles in the system can be unambiguously identified. We also show that
      less mobile particles obey the Stokes-Einstein relation even in the supercooled
      regime and it is the mobile particles which show strong violation of the Stokes
      Einstein relation in agreement with the previous studies on different model glass
      forming systems. Motivated by some of the recent studies where an ideal glass
      transition is proposed by randomly pinning some fraction of particles, we then
      studied the SE breakdown as a function of random pinning concentration in our
      model system. We showed that degree of SE breakdown increases quite dramatically
      with increasing pinning concentration, thereby providing a new way to unravel the
      puzzles of SE violation in supercooled liquids in greater details. 

PMID- 24929406
TI  - Electrostatics of liquid interfaces.
AB  - The standard Maxwell formulation of the problem of polarized dielectrics suffers
      from a number of difficulties, both conceptual and practical. These difficulties
      are particularly significant for liquid interfaces. For these systems, the
      ability of interfacial multipoles to change their orientations leads to the
      interfacial polarization localized within a thin microscopic layer. A formalism
      to capture this physical reality is proposed and is based on the surface charge
      as the source of microscopic electric fields in dielectrics. The surface charge
      density incorporates the local structure of the interface into electrostatic
      calculations. The corresponding surface susceptibility and interface dielectric
      constant provide local closures to the electrostatic boundary value problem. A
      robust approach to calculate the surface susceptibility from numerical
      simulations is formulated. The susceptibility can alternatively be extracted from
      a number of solution experiments, in particular those sensitive to the overall
      dipole moment of a closed dielectric surface. The theory is applied to the
      solvent-induced spectral shift and high-frequency dielectric response of
      solutions. 

PMID- 24929407
TI  - Quasichemical analysis of the cluster-pair approximation for the thermodynamics
      of proton hydration.
AB  - A theoretical analysis of the cluster-pair approximation (CPA) is presented based
      on the quasichemical theory of solutions. The sought single-ion hydration free
      energy of the proton includes an interfacial potential contribution by
      definition. It is shown, however, that the CPA involves an extra-thermodynamic
      assumption that does not guarantee uniform convergence to a bulk free energy
      value with increasing cluster size. A numerical test of the CPA is performed
      using the classical polarizable AMOEBA force field and supporting quantum
      chemical calculations. The enthalpy and free energy differences are computed for
      the kosmotropic Na(+)/F(-) ion pair in water clusters of size n = 5, 25, 105.
      Additional calculations are performed for the chaotropic Rb(+)/I(-) ion pair. A
      small shift in the proton hydration free energy and a larger shift in the
      hydration enthalpy, relative to the CPA values, are predicted based on the n =
      105 simulations. The shifts arise from a combination of sequential hydration and
      interfacial potential effects. The AMOEBA and quantum chemical results suggest an
      electrochemical surface potential of water in the range -0.4 to -0.5 V. The
      physical content of single-ion free energies and implications for ion-water force
      field development are also discussed. 

PMID- 24929408
TI  - Adsorption of probe molecules in pillared interlayered clays: experiment and
      computer simulation.
AB  - In this paper we investigate the adsorption of various probe molecules in order
      to characterize the porous structure of a series of pillared interlayered clays
      (PILC). To that aim, volumetric and microcalorimetric adsorption experiments were
      performed on various Zr PILC samples using nitrogen, toluene, and mesitylene as
      probe molecules. For one of the samples, neutron scattering experiments were also
      performed using toluene as adsorbate. Various structural models are proposed and
      tested by means of a comprehensive computer simulation study, using both
      geometric and percolation analysis in combination with Grand Canonical Monte
      Carlo simulations in order to model the volumetric and microcalorimetric
      isotherms. On the basis of this analysis, we propose a series of structural
      models that aim at accounting for the adsorption experimental behavior, and make
      possible a microscopic interpretation of the role played by the different
      interactions and steric effects in the adsorption processes in these rather
      complex disordered microporous systems. 

PMID- 24929409
TI  - Ab initio investigation of electronic and vibrational contributions to linear and
      nonlinear dielectric properties of ice.
AB  - Electronic and vibrational contributions to the static and dynamic
      (hyper)polarizability tensors of ice XI and model structures of ordinary
      hexagonal ice have been theoretically investigated. Calculations were carried out
      by the finite field nuclear relaxation method for periodic systems (FF-NR)
      recently implemented in the CRYSTAL code, using the coupled-perturbed Kohn-Sham
      approach (CPKS) for evaluating the required electronic properties. The effect of
      structure on the static electronic polarizabilities (dielectric constants) and
      second-hyperpolarizabilities is minimal. On the other hand, the vibrational
      contributions to the polarizabilities were found to be significant. A reliable
      evaluation of these (ionic) contributions allows one to discriminate amongst ice
      phases characterized by different degrees of proton-order, primarily through
      differences caused by librational motions. Transverse static and dynamic
      vibrational (hyper)polarizabilities were found by extrapolating calculations for
      slabs of increasing size, in order to eliminate substantial surface
      contributions. 

PMID- 24929410
TI  - The structural diversity of ABS3 compounds with d0 electronic configuration for
      the B-cation.
AB  - We use first-principles density functional theory within the local density
      approximation to ascertain the ground state structure of real and theoretical
      compounds with the formula ABS3 (A = K, Rb, Cs, Ca, Sr, Ba, Tl, Sn, Pb, and Bi;
      and B = Sc, Y, Ti, Zr, V, and Nb) under the constraint that B must have a d(0)
      electronic configuration. Our findings indicate that none of these AB
      combinations prefer a perovskite ground state with corner-sharing BS6 octahedra,
      but that they prefer phases with either edge- or face-sharing motifs. Further, a
      simple two-dimensional structure field map created from A and B ionic radii
      provides a neat demarcation between combinations preferring face-sharing versus
      edge-sharing phases for most of these combinations. We then show that by
      modifying the common Goldschmidt tolerance factor with a multiplicative term
      based on the electronegativity difference between A and S, the demarcation
      between predicted edge-sharing and face-sharing ground state phases is enhanced.
      We also demonstrate that, by calculating the free energy contribution of phonons,
      some of these compounds may assume multiple phases as synthesis temperatures are
      altered, or as ambient temperatures rise or fall. 

PMID- 24929411
TI  - Predicted boron-carbide compounds: a first-principles study.
AB  - By using developed particle swarm optimization algorithm on crystal structural
      prediction, we have explored the possible crystal structures of B-C system. Their
      structures, stability, elastic properties, electronic structure, and chemical
      bonding have been investigated by first-principles calculations with density
      functional theory. The results show that all the predicted structures are
      mechanically and dynamically stable. An analysis of calculated enthalpy with
      pressure indicates that increasing of boron content will increase the stability
      of boron carbides under low pressure. Moreover, the boron carbides with rich
      carbon content become more stable under high pressure. The negative formation
      energy of predicted B5C indicates its high stability. The density of states of
      B5C show that it is p-type semiconducting. The calculated theoretical Vickers
      hardnesses of B-C exceed 40 GPa except B4C, BC, and BC4, indicating they are
      potential superhard materials. An analysis of Debye temperature and electronic
      localization function provides further understanding chemical and physical
      properties of boron carbide. 

PMID- 24929412
TI  - Polymorphism and thermodynamic ground state of silver fulminate studied from van
      der Waals density functional calculations.
AB  - Silver fulminate (AgCNO) is a primary explosive, which exists in two polymorphic
      phases, namely, orthorhombic (Cmcm) and trigonal (R3) forms at ambient
      conditions. In the present study, we have investigated the effect of pressure and
      temperature on relative phase stability of the polymorphs using planewave
      pseudopotential approaches based on Density Functional Theory (DFT). van der
      Waals interactions play a significant role in predicting the phase stability and
      they can be effectively captured by semi-empirical dispersion correction methods
      in contrast to standard DFT functionals. Based on our total energy calculations
      using DFT-D2 method, the Cmcm structure is found to be the preferred
      thermodynamic equilibrium phase under studied pressure and temperature range.
      Hitherto Cmcm and R3 phases denoted as alpha- and beta-forms of AgCNO,
      respectively. Also a pressure induced polymorphic phase transition is seen using
      DFT functionals and the same was not observed with DFT-D2 method. The equation of
      state and compressibility of both polymorphic phases were investigated.
      Electronic structure and optical properties were calculated using full potential
      linearized augmented plane wave method within the Tran-Blaha modified Becke
      Johnson potential. The calculated electronic structure shows that alpha, beta
      phases are indirect bandgap insulators with a bandgap values of 3.51 and 4.43 eV,
      respectively. The nature of chemical bonding is analyzed through the charge
      density plots and partial density of states. Optical anisotropy, electric-dipole
      transitions, and photo sensitivity to light of the polymorphs are analyzed from
      the calculated optical spectra. Overall, the present study provides an early
      indication to experimentalists to avoid the formation of unstable beta-form of
      AgCNO.

PMID- 24929413
TI  - Computational study on ice growth inhibition of Antarctic bacterium antifreeze
      protein using coarse grained simulation.
AB  - Antarctic bacterium antifreeze proteins (AFPs) protect and support the survival
      of cold-adapted organisms by binding and inhibiting the growth of ice crystals.
      The mechanism of the anti-freezing process in a water environment at low
      temperature of Antarctic bacterium AFPs remains unclear. In this research, we
      study the effects of Antarctic bacterium AFPs by coarse grained simulations
      solution at a temperature range from 262 to 273 K. The results indicated that
      Antarctic bacterium AFPs were fully active in temperatures greater than 265 K.
      Additionally, the specific temperature ranges at which the water molecules become
      completely frozen, partially frozen, and not frozen were identified. 

PMID- 24929414
TI  - Relationship between beta-relaxation and structural stability of lysozyme:
      microscopic insight on thermostabilization mechanism by trehalose from Raman
      spectroscopy experiments.
AB  - Raman investigations were carried out in the low-frequency and amide I regions on
      lysozyme aqueous solutions in absence and presence of trehalose. Raman
      spectroscopy gives the unique opportunity to analyze the protein and solvent
      dynamics in the low-frequency range while monitoring the unfolding process by
      capturing the spectrum of the amide I band. From the analysis of the quasielastic
      intensity, a dynamic change is firstly observed in a highly hydrated protein,
      around 70  degrees C, and interpreted in relation with the denaturation mechanism
      of the protein. The use of heavy water and partly deuterated trehalose gives
      clear information on protein-trehalose interactions in the native state of
      lysozyme (at room temperature) and during the thermal denaturation process of
      lysozyme. At room temperature, it was found that trehalose is preferentially
      excluded from the protein surface, and has a main effect on the tetrahedral local
      order of water molecules corresponding to a stiffening of the H-bond network in
      the solvent. The consequence is a significant reduction of the amplitude of fast
      relaxational motions, inducing a less marked dynamic transition shifted toward
      the high temperatures. Upon heating, interaction between trehalose and lysozyme
      is detected during the solvent penetration within the protein, i.e., while the
      native globular state softens into a molten globule (MG) state. Addition of
      trehalose reduces the protein flexibility in the MG state, improving the
      structural stability of the protein, and inhibiting the protein aggregation. 

PMID- 24929415
TI  - Endohedral confinement of a DNA dodecamer onto pristine carbon nanotubes and the
      stability of the canonical B form.
AB  - Although carbon nanotubes are potential candidates for DNA encapsulation and
      subsequent delivery of biological payloads to living cells, the thermodynamical
      spontaneity of DNA encapsulation under physiological conditions is still a matter
      of debate. Using enhanced sampling techniques, we show for the first time that,
      given a sufficiently large carbon nanotube, the confinement of a double-stranded
      DNA segment, 5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3', is thermodynamically
      favourable under physiological environments (134 mM, 310 K, 1 bar), leading to
      DNA-nanotube hybrids with lower free energy than the unconfined biomolecule. A
      diameter threshold of 3 nm is established below which encapsulation is inhibited.
      The confined DNA segment maintains its translational mobility and exhibits the
      main geometrical features of the canonical B form. To accommodate itself within
      the nanopore, the DNA's end-to-end length increases from 3.85 nm up to
      approximately 4.1 nm, due to a ~0.3 nm elastic expansion of the strand termini.
      The canonical Watson-Crick H-bond network is essentially conserved throughout
      encapsulation, showing that the contact between the DNA segment and the
      hydrophobic carbon walls results in minor rearrangements of the nucleotides H
      bonding. The results obtained here are paramount to the usage of carbon nanotubes
      as encapsulation media for next generation drug delivery technologies.

PMID- 24929416
TI  - Comment on "Communication: Benzene dimer--the free energy landscape" [J. Chem.
      Phys. 139, 201102 (2013)].

PMID- 24929417
TI  - Response to "Comment on 'Communication: Benzene dimer--the free energy
      landscape'" [J. Chem. Phys. 140, 227101 (2014)].

PMID- 24929422
TI  - Polyamine-responsive ribosomal arrest at the stop codon of an upstream open
      reading frame of the AdoMetDC1 gene triggers nonsense-mediated mRNA decay in
      Arabidopsis thaliana.
AB  - During mRNA translation, nascent peptides with certain specific sequences cause
      arrest of ribosomes that have synthesized themselves. In some cases, such
      ribosomal arrest is coupled with mRNA decay. In yeast, mRNA quality control
      systems have been shown to be involved in mRNA decay associated with ribosomal
      arrest. However, a link between ribosomal arrest and mRNA quality control systems
      has not been found in multicellular organisms. In this study, we aimed to explore
      the relationship between ribosomal arrest and mRNA decay in plants. For this
      purpose, we used an upstream open reading frame (uORF) of the Arabidopsis
      thaliana AdoMetDC1 gene, in which the uORF-encoded peptide is involved in
      polyamine-responsive translational repression of the main coding sequence. Our in
      vitro analyses revealed that the AdoMetDC1 uORF-encoded peptide caused ribosomal
      arrest at the uORF stop codon in response to polyamine. Using transgenic calli
      harboring an AdoMetDC1 uORF-containing reporter gene, we showed that polyamine
      promoted mRNA decay in a uORF sequence-dependent manner. These results suggest
      that the polyamine-responsive ribosomal arrest mediated by the uORF-encoded
      peptide is coupled with mRNA decay. Our results also showed that the polyamine
      responsive acceleration of mRNA decay was compromised by defects in factors that
      are essential for nonsense-mediated mRNA decay (NMD), an mRNA quality control
      system that degrades mRNAs with premature stop codons, suggesting that NMD is
      involved in AdoMetDC1 uORF peptide-mediated mRNA decay. Collectively, these
      findings suggest that AdoMetDC1 uORF peptide-mediated ribosomal arrest at the
      uORF stop codon induces NMD. 

PMID- 24929423
TI  - Wide-range high-resolution transmission electron microscopy reveals morphological
      and distributional changes of endomembrane compartments during log to stationary
      transition of growth phase in tobacco BY-2 cells.
AB  - Rapid growth of plant cells by cell division and expansion requires an
      endomembrane trafficking system. The endomembrane compartments, such as the Golgi
      stacks, endosome and vesicles, are important in the synthesis and trafficking of
      cell wall materials during cell elongation. However, changes in the morphology,
      distribution and number of these compartments during the different stages of cell
      proliferation and differentiation have not yet been clarified. In this study, we
      examined these changes at the ultrastructural level in tobacco Bright yellow 2
      (BY-2) cells during the log and stationary phases of growth. We analyzed images
      of the BY-2 cells prepared by the high-pressure freezing/freeze substitution
      technique with the aid of an auto-acquisition transmission electron microscope
      system. We quantified the distribution of secretory and endosomal compartments in
      longitudinal sections of whole cells by using wide-range gigapixel-class images
      obtained by merging thousands of transmission electron micrographs. During the
      log phase, all Golgi stacks were composed of several thick cisternae.
      Approximately 20 vesicle clusters (VCs), including the trans-Golgi network and
      secretory vesicle cluster, were observed throughout the cell. In the stationary
      phase cells, Golgi stacks were thin with small cisternae, and only a few VCs were
      observed. Nearly the same number of multivesicular body and small high-density
      vesicles were observed in both the stationary and log phases. Results from
      electron microscopy and live fluorescence imaging indicate that the morphology
      and distribution of secretory-related compartments dramatically change when cells
      transition from log to stationary phases of growth. 

PMID- 24929424
TI  - Transcriptional control of GABAergic neuronal subtype identity in the thalamus.
AB  - BACKGROUND: The thalamus is often defined as the 'gateway to consciousness', a
      feature that is supported by the specific connectivity and electrophysiological
      properties of its neurons. Inhibitory GABAergic neurons are required for the
      dynamic gating of information passing through the thalamus. The high degree of
      heterogeneity among thalamic GABA neurons suggests that, during embryonic
      development, alternative differentiation programmes exist to guide the
      acquisition of inhibitory neuron subtype identity. RESULTS: Taking advantage of
      the accessibility of the developing chick embryo, we have used in ovo
      manipulations of gene expression to test the role of candidate transcription
      factors in controlling GABAergic neuronal subtype identity in the developing
      thalamus. CONCLUSIONS: In this study, we describe two alternative differentiation
      programmes for GABAergic neurogenesis in the thalamus and identify Helt and Dlx2
      as key transcription factors that are sufficient to direct neuronal progenitors
      along a specific differentiation pathway at the expense of alternative lineage
      choices. Furthermore, we identify Calb2, a gene encoding for the GABA subtype
      marker calretinin as a target of the transcription factor Sox14. This work is a
      step forward in our understanding of how GABA neuron diversity in the thalamus is
      achieved during development and will help future investigation of the molecular
      mechanisms that lead up to the acquisition of different synaptic targets and
      electrophysiological features of mature thalamic inhibitory neurons.

PMID- 24929425
TI  - Evidence of weak genetic structure and recent gene flow between Bactrocera
      dorsalis s.s. and B. papayae, across Southern Thailand and West Malaysia,
      supporting a single target pest for SIT applications.
AB  - BACKGROUND: Bactrocera dorsalis s.s. (Hendel) and B. papayae Drew & Hancock, are
      invasive pests belonging to the B. dorsalis complex. Their species status, based
      on morphology, is sometimes arguable. Consequently, the existence of cryptic
      species and/or population isolation may decrease the effectiveness of the sterile
      insect technique (SIT) due to an unknown degree of sexual isolation between
      released sterile flies and wild counterparts. To evaluate the genetic
      relationship and current demography in wild populations for guiding the
      application of area-wide integrated pest management using SIT, seven
      microsatellite-derived markers from B. dorsalis s.s. and another five from B.
      papayae were used for surveying intra- and inter-specific variation, population
      structure, and recent migration among sympatric and allopatric populations of the
      two morphological forms across Southern Thailand and West Malaysia. RESULTS:
      Basic genetic variations were not significantly different among forms,
      populations, and geographical areas (P > 0.05). Nonetheless, two sets of
      microsatellite markers showed significantly different levels of polymorphisms.
      Genetic differentiation between intra- and inter-specific differences was
      significant, but low. Seventeen populations revealed three hypothetical genetic
      clusters (K = 3) regardless of forms and geographical areas. The genetic
      structure of sympatric populations slightly changed during the different years of
      collection. Recent gene flow (m >= 0.10) was frequently detected whether samples
      were sympatric or allopatric. Ninety-five of 379 individuals distributed across
      the given area were designated as recent migrants or of admixed ancestry. As a
      consequence of substantial migration, no significant correlation between genetic
      and geographic distances was detected (R2 = 0.056, P = 0.650). CONCLUSIONS:
      According to the 12 microsatellite variations, weak population structure and
      recent gene flow suggest that there is no status for cryptic species between B.
      dorsalis s.s. and B. papayae forms in Southern Thailand and West Malaysia. Both
      forms can be treated as a single target pest for the SIT program in an area-wide
      sense. Additionally, the result of species identification based on molecular data
      and morphological character are not congruent. The use of independent, multiple
      approaches in the characterization of the target population may ensure the
      effectiveness and feasibility of SIT-based control in the target area.

PMID- 24929426
TI  - FastaValidator: an open-source Java library to parse and validate FASTA formatted
      sequences.
AB  - BACKGROUND: Advances in sequencing technologies challenge the efficient importing
      and validation of FASTA formatted sequence data which is still a prerequisite for
      most bioinformatic tools and pipelines. Comparative analysis of commonly used
      Bio*-frameworks (BioPerl, BioJava and Biopython) shows that their scalability and
      accuracy is hampered. FINDINGS: FastaValidator represents a platform-independent,
      standardized, light-weight software library written in the Java programming
      language. It targets computer scientists and bioinformaticians writing software
      which needs to parse quickly and accurately large amounts of sequence data. For
      end-users FastaValidator includes an interactive out-of-the-box validation of
      FASTA formatted files, as well as a non-interactive mode designed for high
      throughput validation in software pipelines. CONCLUSIONS: The accuracy and
      performance of the FastaValidator library qualifies it for large data sets such
      as those commonly produced by massive parallel (NGS) technologies. It offers
      scientists a fast, accurate and standardized method for parsing and validating
      FASTA formatted sequence data.

PMID- 24929427
TI  - Disease-specific outcomes of radical prostatectomies in Northern Norway; a case
      for the impact of perineural infiltration and postoperative PSA-doubling time.
AB  - BACKGROUND: Prostate cancer is the most common male malignancy and a mayor cause
      of mortality in the western world. The impact of clinicopathological variables on
      disease related outcomes have mainly been reported from a few large US series,
      most of them not reporting on perineural infiltration. We therefore wanted to
      investigate relevant cancer outcomes in patients undergoing radical prostatectomy
      in two Norwegian health regions with an emphasis on the impact of perineural
      infiltration (PNI) and prostate specific antigen- doubling time (PSA-DT).
      METHODS: We conducted a retrospective analysis of 535 prostatectomy patients at
      three hospitals between 1995 and 2005 estimating biochemical failure- (BFFS),
      clinical failure- (CFFS) and prostate cancer death-free survival (PCDFS) with the
      Kaplan-Meier method. We investigated clinicopathological factors influencing risk
      of events using cox proportional hazard regression. RESULTS: After a median
      follow-up of 89 months, 170 patients (32%) experienced biochemical failure (BF),
      36 (7%) experienced clinical failure and 15 (3%) had died of prostate cancer. pT
      Stage (p = 0.001), preoperative PSA (p = 0.047), Gleason Score (p = 0.032), non
      apical positive surgical margins (PSM) (p = 0.003) and apical PSM (p = 0.031)
      were all independently associated to BFFS. Gleason score (p = 0.019), PNI (p =
      0.012) and non-apical PSM (p = 0.002) were all independently associated to CFFS
      while only PNI (P = 0.047) and subgroups of Gleason score were independently
      associated to PCDFS. After BF, patients with a shorter PSA-DT had independent and
      significant worse event-free survivals than patients with PSA-DT > 15 months (PSA
      DT = 3-9 months, CFFS HR = 6.44, p < 0.001, PCDFS HR = 13.7, p = 0.020; PSA-DT <
      3 months, CFFS HR = 11.2, p < 0.001, PCDFS HR = 27.5, p = 0.006). CONCLUSIONS:
      After prostatectomy, CFFS and PCDFS are variable, but both are strongly
      associated to Gleason score and PNI. In patients with BF, PSA-DT was most
      strongly associated to CF and PCD. Our study adds weight to the importance of PSA
      DT and re-launches PNI as a strong prognosticator for clinically relevant
      endpoints.

PMID- 24929428
TI  - Effect of lowering the glycemic load with canola oil on glycemic control and
      cardiovascular risk factors: a randomized controlled trial.
AB  - OBJECTIVE: Despite their independent cardiovascular disease (CVD) advantages,
      effects of alpha-linolenic acid (ALA), monounsaturated fatty acid (MUFA), and low
      glycemic-load (GL) diets have not been assessed in combination. We therefore
      determined the combined effect of ALA, MUFA, and low GL on glycemic control and
      CVD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS: The study was a
      parallel design, randomized trial wherein each 3-month treatment was conducted in
      a Canadian academic center between March 2011 and September 2012 and involved 141
      participants with type 2 diabetes (HbA1c 6.5%-8.5% [48-69 mmol/mol]) treated with
      oral antihyperglycemic agents. Participants were provided with dietary advice on
      either a low-GL diet with ALA and MUFA given as a canola oil-enriched bread
      supplement (31 g canola oil per 2,000 kcal) (test) or a whole-grain diet with a
      whole-wheat bread supplement (control). The primary outcome was HbA1c change.
      Secondary outcomes included calculated Framingham CVD risk score and reactive
      hyperemia index (RHI) ratio. RESULTS: Seventy-nine percent of the test group and
      90% of the control group completed the trial. The test diet reduction in HbA1c
      units of -0.47% (-5.15 mmol/mol) (95% CI -0.54% to -0.40% [-5.92 to -4.38
      mmol/mol]) was greater than that for the control diet (-0.31% [-3.44 mmol/mol]
      [95% CI -0.38% to -0.25% (-4.17 to -2.71 mmol/mol)], P = 0.002), with the
      greatest benefit observed in those with higher systolic blood pressure (SBP).
      Greater reductions were seen in CVD risk score for the test diet, whereas the RHI
      ratio increased for the control diet. CONCLUSIONS: A canola oil-enriched low-GL
      diet improved glycemic control in type 2 diabetes, particularly in participants
      with raised SBP, whereas whole grains improved vascular reactivity.

PMID- 24929429
TI  - Safety of outpatient closed-loop control: first randomized crossover trials of a
      wearable artificial pancreas.
AB  - OBJECTIVE: We estimate the effect size of hypoglycemia risk reduction on closed
      loop control (CLC) versus open-loop (OL) sensor-augmented insulin pump therapy in
      supervised outpatient setting. RESEARCH DESIGN AND METHODS: Twenty patients with
      type 1 diabetes initiated the study at the Universities of Virginia, Padova, and
      Montpellier and Sansum Diabetes Research Institute; 18 completed the entire
      protocol. Each patient participated in two 40-h outpatient sessions, CLC versus
      OL, in randomized order. Sensor (Dexcom G4) and insulin pump (Tandem t:slim) were
      connected to Diabetes Assistant (DiAs)-a smartphone artificial pancreas platform.
      The patient operated the system through the DiAs user interface during both CLC
      and OL; study personnel supervised on site and monitored DiAs remotely. There
      were no dietary restrictions; 45-min walks in town and restaurant dinners were
      included in both CLC and OL; alcohol was permitted. RESULTS: The primary outcome
      reduction in risk for hypoglycemia as measured by the low blood glucose (BG)
      index (LGBI)-resulted in an effect size of 0.64, P = 0.003, with a twofold
      reduction of hypoglycemia requiring carbohydrate treatment: 1.2 vs. 2.4
      episodes/session on CLC versus OL (P = 0.02). This was accompanied by a slight
      decrease in percentage of time in the target range of 3.9-10 mmol/L (66.1 vs.
      70.7%) and increase in mean BG (8.9 vs. 8.4 mmol/L; P = 0.04) on CLC versus OL.
      CONCLUSIONS: CLC running on a smartphone (DiAs) in outpatient conditions reduced
      hypoglycemia and hypoglycemia treatments when compared with sensor-augmented pump
      therapy. This was accompanied by marginal increase in average glycemia resulting
      from a possible overemphasis on hypoglycemia safety.

PMID- 24929430
TI  - Improved glucose control with weight loss, lower insulin doses, and no increased
      hypoglycemia with empagliflozin added to titrated multiple daily injections of
      insulin in obese inadequately controlled type 2 diabetes.
AB  - OBJECTIVE: We investigated the efficacy and safety of the sodium glucose
      cotransporter 2 inhibitor, empagliflozin, added to multiple daily injections of
      insulin (MDI insulin) in obese patients with type 2 diabetes mellitus (T2DM).
      RESEARCH DESIGN AND METHODS: Patients inadequately controlled on MDI insulin +/-
      metformin (mean HbA1c 8.3% [67 mmol/mol]; BMI 34.8 kg/m(2); insulin dose 92
      international units/day) were randomized and treated with once-daily
      empagliflozin 10 mg (n = 186), empagliflozin 25 mg (n = 189), or placebo (n =
      188) for 52 weeks. Insulin dose was to remain stable in weeks 1-18, adjusted to
      meet glucose targets in weeks 19-40, then stable in weeks 41-52. The primary end
      point was change from baseline in HbA1c at week 18. Secondary end points were
      changes from baseline in insulin dose, weight, and HbA1c at week 52. RESULTS:
      Adjusted mean +/- SE changes from baseline in HbA1c were -0.50 +/- 0.05% (-5.5 +/
      0.5 mmol/mol) for placebo versus -0.94 +/- 0.05% (-10.3 +/- 0.5 mmol/mol) and 
      1.02 +/- 0.05% (-11.1 +/- 0.5 mmol/mol) for empagliflozin 10 mg and empagliflozin
      25 mg, respectively, at week 18 (both P < 0.001). At week 52, further reductions
      with insulin titration resulted in changes from baseline in HbA1c of -0.81 +/-
      0.08% (-8.9 +/- 0.9 mmol/mol), -1.18 +/- 0.08% (-12.9 +/- 0.9 mmol/mol), and 
      1.27 +/- 0.08% (-13.9 +/- 0.9 mmol/mol) with placebo, empagliflozin 10 mg, and
      empagliflozin 25 mg, respectively, and final HbA1c of 7.5% (58 mmol/mol), 7.2%
      (55 mmol/mol), and 7.1% (54 mmol/mol), respectively. More patients attained HbA1c
      <7% (<53 mmol/mol) with empagliflozin (31-42%) versus placebo (21%; both P <
      0.01). Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses (-9 to 
      11 international units/day) and weight (-2.4 to -2.5 kg) versus placebo (all P <
      0.01) at week 52. CONCLUSIONS: In obese, difficult-to-treat patients with T2DM
      inadequately controlled on high MDI insulin doses, empagliflozin improved
      glycemic control and reduced weight without increasing the risk of hypoglycemia
      and with lower insulin requirements.

PMID- 24929431
TI  - Glucose-lowering effects and low risk of hypoglycemia in patients with maturity
      onset diabetes of the young when treated with a GLP-1 receptor agonist: a double
      blind, randomized, crossover trial.
AB  - OBJECTIVE: The most common form of maturity-onset diabetes of the young (MODY),
      hepatocyte nuclear factor 1alpha (HNF1A diabetes: MODY3) is often treated with
      sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment
      with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A diabetes. RESEARCH
      DESIGN AND METHODS: Sixteen patients with HNF1A diabetes (8 women; mean age 39
      years [range 23-67 years]; BMI 24.9 +/- 0.5 kg/m(2) [mean +/- SEM]; fasting
      plasma glucose [FPG] 9.9 +/- 0.9 mmol/L; HbA1c 6.4 +/- 0.2% [47 +/- 3 mmol/mol])
      received 6 weeks of treatment with a GLP-1RA (liraglutide) and placebo (tablets),
      as well as a sulfonylurea (glimepiride) and placebo (injections), in randomized
      order, in a double-blind, crossover trial. Glimepiride was up-titrated once
      weekly in a treat-to-target manner; liraglutide was up-titrated once weekly to
      1.8 mg once daily. At baseline and at the end of each treatment period a
      standardized liquid meal test was performed, including a 30-min light bicycle
      test. RESULTS: FPG decreased during the treatment periods (-1.6 +/- 0.5 mmol/L
      liraglutide [P = 0.012] and -2.8 +/- 0.7 mmol/L glimepiride [P = 0.003]), with no
      difference between treatments (P = 0.624). Postprandial plasma glucose (PG)
      responses (total area under the curve) were lower with both glimepiride (2,136 +/
      292 min * mmol/L) and liraglutide (2,624 +/- 340 min * mmol/L) compared with
      baseline (3,127 +/- 291 min * mmol/L; P < 0.001, glimepiride; P = 0.017,
      liraglutide), with no difference between treatments (P = 0.121). Eighteen
      episodes of hypoglycemia (PG <=3.9 mmol/L) occurred during glimepiride treatment
      and one during liraglutide treatment. CONCLUSIONS: Six weeks of treatment with
      glimepiride or liraglutide lowered FPG and postprandial glucose excursions in
      patients with HNF1A diabetes. The glucose-lowering effect was greater with
      glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.

PMID- 24929433
TI  - Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of
      over 5000 cases from 10 specialized hospitals.
AB  - BACKGROUND: The global burden from cancer is rising, especially as low-income
      countries like Bangladesh observe rapid aging. So far, there are no comprehensive
      descriptions reporting diagnosed cancer group that include hematological
      malignancies in Bangladesh. METHODS: This was a multi-center hospital-based
      retrospective descriptive study of over 5000 confirmed hematological cancer cases
      in between January 2008 to December 2012. Morphological typing was carried out
      using the "French American British" classification system. RESULTS: A total of
      5013 patients aged between 2 to 90 years had been diagnosed with malignant
      hematological disorders. A 69.2% were males (n=3468) and 30.8% females (n=1545),
      with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42
      years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35
      years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non
      Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia
      (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years),
      myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin's lymphoma
      (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia
      (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic
      leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%).
      Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older
      patients, aged 50-over. CONCLUSIONS: For the first time, our study presents the
      pattern and distribution of diagnosed hematological cancers in Bangladesh. It
      shows differences in population distributions as compared to other settings with
      possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting
      of affected women. Further studies are necessary on the epidemiology, genetics
      and potential environmental risk factors within this rapidly aging country.

PMID- 24929434
TI  - An innovative system for 3D clinical photography in the resource-limited
      settings.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is the most frequently occurring cancer in
      Mozambique among men and the second most frequently occurring cancer among women.
      Effective therapeutic treatments for KS are poorly understood in this area. There
      is an unmet need to develop a simple but accurate tool for improved monitoring
      and diagnosis in a resource-limited setting. Standardized clinical photographs
      have been considered to be an essential part of the evaluation. METHODS: When a
      therapeutic response is achieved, nodular KS often exhibits a reduction of the
      thickness without a change in the base area of the lesion. To evaluate the
      vertical space along with other characters of a KS lesion, we have created an
      innovative imaging system with a consumer light-field camera attached to a
      miniature "photography studio" adaptor. The image file can be further processed
      by computational methods for quantification. RESULTS: With this novel imaging
      system, each high-quality 3D image was consistently obtained with a single camera
      shot at bedside by minimally trained personnel. After computational processing,
      all-focused photos and measurable 3D parameters were obtained. More than 80 KS
      image sets were processed in a semi-automated fashion. CONCLUSIONS: In this proof
      of-concept study, the feasibility to use a simple, low-cost and user-friendly
      system has been established for future clinical study to monitor KS therapeutic
      response. This 3D imaging system can be also applied to obtain standardized
      clinical photographs for other diseases.

PMID- 24929435
TI  - Sarcopenia is a predictor of outcomes in very elderly patients undergoing
      emergency surgery.
AB  - BACKGROUND: With the increasing aging population, the number of very elderly
      patients (age >=80 years) undergoing emergency operations is increasing.
      Evaluating patient-specific risk factors for postoperative morbidity and
      mortality in the acute care surgery setting is crucial to improving outcomes. We
      hypothesize that sarcopenia, a severe depletion of skeletal muscles, is a
      predictor of morbidity and mortality in very elderly patients undergoing
      emergency surgery. METHODS: A total of 170 patients older than the age of 80
      underwent emergency surgery between 2008 and 2010 at a tertiary care facility;
      100 of these patients had abdominal computed tomography images within 30 days of
      the operation that were adequate for the assessment of sarcopenia. The impact of
      sarcopenia on the operative outcomes was evaluated using both univariate and
      multivariate analysis. RESULTS: The mean patient age was 84 years, with an in
      hospital mortality of 18%. Sarcopenia was present in 73% of patients. More
      sarcopenic patients had postoperative complications (45% sarcopenic versus 15%
      nonsarcopenic, P = .005) and more died in hospital (23 vs 4%, P = .037). There
      were no differences in duration of stay or requirement for intensive care unit
      postoperatively. After we controlled for confounding factors, increasing skeletal
      muscle index (per incremental cm(2)/m(2)) was associated with decreased in
      hospital mortality (odds ratio ~0.834, 95% confidence interval 0.731-0.952, P =
      .007) in multivariate analysis. CONCLUSION: Sarcopenia was independently
      predictive of greater complication rates, discharge disposition, and in-hospital
      mortality in the very elderly emergency surgery population. Using sarcopenia as
      an objective tool to identify high-risk patients would be beneficial in
      developing tailored preventative strategies and potentially resource allocation
      in the future.

PMID- 24929436
TI  - Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding
      RNAs.
AB  - Long noncoding RNAs (lncRNAs) are important regulators of cell fate, yet little
      is known about mechanisms controlling lncRNA expression. Here we show that
      transcription is quantitatively different for lncRNAs and mRNAs--as revealed by
      deficiency of Dicer (Dcr), a key RNase that generates microRNAs (miRNAs). Dcr
      loss in mouse embryonic stem cells led unexpectedly to decreased levels of
      hundreds of lncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust
      lncRNA transcriptional initiation and elongation. Computational and genetic
      epistasis analyses demonstrated that Dcr activation of the oncogenic
      transcription factor cMyc is partly responsible for lncRNA expression. A
      quantitative metric of mRNA-lncRNA decoupling revealed that Dcr and cMyc
      differentially regulate lncRNAs versus mRNAs in diverse cell types and in vivo.
      Thus, numerous lncRNAs may be modulated as a class in development and disease,
      notably where Dcr and cMyc act.

PMID- 24929437
TI  - The translational landscape of fission-yeast meiosis and sporulation.
AB  - Sexual development in Schizosaccharomyces pombe culminates in meiosis and
      sporulation. We used ribosome profiling to investigate the translational
      landscape of this process. We show that the translation efficiency of hundreds of
      genes is regulated in complex patterns, often correlating with changes in RNA
      levels. Ribosome-protected fragments show a three-nucleotide periodicity that
      identifies translated sequences and their reading frame. Using this property, we
      identified 46 new translated genes and found that 24% of noncoding RNAs are
      actively translated. We also detected 19 nested antisense genes, in which both
      DNA strands encode translated mRNAs. Finally, we identified 1,735 translated
      upstream open reading frames (ORFs) in leader sequences. In S. pombe, in contrast
      with Saccharomyces cerevisiae, sexual development is not accompanied by large
      increases in upstream ORF use, thus suggesting that this is an organism-specific
      adaptation, not a general feature of developmental processes. 

PMID- 24929438
TI  - Evaluation of the spatial and temporal distribution of and risk factors for
      Bluetongue serotype 1 epidemics in sheep Extremadura (Spain), 2007-2011.
AB  - Extremadura has been one of the regions in Spain most severely affected by
      Bluetongue (BT) epidemics. The first incursion of BTV, which was successfully
      eradicated one year later, occurred in 2004, involving the BTV-serotype 4.
      However, a second incursion occurred in September 2007, this time involving
      serotype 1. Since then, the implementation of intensive vaccination programs have
      significantly reduced BTV-1 occurrence, but the disease has not been completely
      eradicated yet. This study aimed to provide, for the first time, a complete
      description of the spatial and temporal patterns of BTV-1 occurrence in sheep in
      Extremadura from 2007 to 2011 and to identify the risk factors that contributed
      to the seasonal occurrence of BTV-1 in this region. The results showed that risk
      factors contributing to BTV-1 occurrence in sheep changed between 2007 and 2011.
      Initially, when the population was still immunologically naive, the main risk
      factors for BTV-1 occurrence were extensive management practices, large sheep
      farms and Culicoides abundance on farms. However, after the implementation of
      vaccination, other factors became more relevant for BTV-1 occurrence, mostly
      related to BTV reservoirs, such as the proximity of cattle farms or the
      introduction of cattle into farms. The Talaverana sheep breed also seemed to be
      associated with a significantly higher risk of BTV-1 occurrence, although it may
      be due to confounding factors, such as the geographical concentration of where
      this breed is kept and/or management practises used for this breed. The results
      of this study suggest that preventive and control strategies, including
      vaccination and active surveillance strategies, should be primarily focused on
      cattle farms kept in close vicinity to sheep flocks as well as in high-risk sheep
      farms (i.e. farms with a large farm size keeping both cattle and sheep and with a
      high number of animal introductions). Methods and results presented here may be
      used to guide decisions for the annual update of the control and eradication
      program in Spain. 

PMID- 24929439
TI  - Ellagic acid inhibits adipocyte differentiation through coactivator-associated
      arginine methyltransferase 1-mediated chromatin modification.
AB  - Chromatin remodeling is a key mechanism in adipocyte differentiation. However, it
      is unknown whether dietary polyphenols are epigenetic effectors for adiposity
      control. Ellagic acid (EA) is a naturally occurring polyphenol in numerous fruits
      and vegetables. Recently, EA-containing foods have been reported to reduce
      adiposity. In the present study, we sought to determine whether EA inhibits
      adipogenesis by modifying chromatin remodeling in human adipogenic stem cells
      (hASCs). qPCR microarray of chromatin modification enzymes revealed that 10
      MUmol/L of EA significantly inhibits histone deacetylase (HDAC)9 down-regulation.
      In addition, EA was associated with up-regulation of HDAC activity and a marked
      reduction of histone acetylation levels. However, chemical inhibition of HDAC
      activity or depletion of HDAC9 by siRNA were not sufficient to reverse the
      antiadipogenic effects of EA. Intriguingly, EA treatment was also associated with
      reduced histone 3 arginine 17 methylation levels (H3R17me2), implying the
      inhibitory role of EA in coactivator-associated arginine methyltransferase 1
      (CARM)1 activity during adipogenesis. Boosting CARM1 activity by delivering cell
      penetrating peptides of CARM1 not only recovered H3R17me2 but also restored
      adipogenesis evidenced by H3 acetylation at lysine 9, HDAC9 down-regulation,
      PPARgamma expression and triglyceride accumulation. Taken together, our data
      suggest that reduced CARM1 activity by EA results in a decrease of H3R17me2
      levels, which may interrupt consecutive histone remodeling steps for adipocyte
      differentiation including histone acetylation and HDAC9 dissociation from
      chromatin. Our work provides the mechanistic insights into how EA, a polyphenol
      ubiquitously found in fruits and vegetables, attenuates human adipocyte
      differentiation by altering chromatin remodeling.

PMID- 24929440
TI  - Changes in physical activity, physical fitness, self-perception and quality of
      life following a 6-month physical activity counseling and cognitive behavioral
      therapy program in outpatients with binge eating disorder.
AB  - The aim of the current study was to explore the associations between changes in
      the number of binges, physical activity participation, physical fitness, physical
      self-perception and quality of life following a 6-month physical activity
      counseling and cognitive behavioral program in patients with binge eating
      disorder (BED). In total 34 (31 women) outpatients with BED (38.5+/-10.7 years)
      completed a 6-month 1-day per week group-based program. Participants completed
      the 36-item Short Form Health Survey, the Baecke Physical Activity questionnaire,
      the Physical Self Perception Profile and performed a 6-min walk test (6MWT) at
      baseline, after 3 and 6 months. Except for physical activity at work, physical
      strength and self-worth perception, all parameters significantly improved after 6
      months. The effect sizes ranged from -0.33 for the number of binges to 1.67 for
      participation in sports activities. Significant increases in leisure time
      physical activity were associated with significant improvements in physical
      health related quality of life, perceived sports competence and physical fitness
      and in perceived body attractiveness. The significant reduction in the number of
      binges was associated with significant improvements in physical health related
      quality of life. Future research should focus on detailing which techniques can
      stimulate physical activity participation in patients with BED. 

PMID- 24929441
TI  - A professional duty to contribute toward preventing unsafe abortion and its
      consequences.

PMID- 24929442
TI  - The detection of coronary stiffness in cardiac allografts using MR imaging.
AB  - OBJECTIVE: To test the hypothesis that biomechanical changes are quantitatively
      related to morphological features of coronary arteries in heart transplant (HTx)
      recipients. MATERIALS AND METHODS: With IRB approval, three-dimensional (3D)
      magnetic resonance (MR) angiography and two-dimensional (2D) black-blood stead
      state free precession (SSFP) MR imaging were performed to image coronary arteries
      of 36 HTx patients. Contours of coronary wall were manually drawn. For each
      coronary segment, coronary wall thickness, wall area, lumen area (in systole and
      diastole) were acquired. Coronary distensibility index (CDI) and the percent of
      the coronary wall occupying the vessel area (PWOV) were calculated. RESULTS:
      There are totally 98 coronary segments eligible for quantitative analysis from 27
      HTx patients. The CDI is 4.90 +/- 2.44 mmHg(-1). The mean wall thickness is 1.49
      +/- 0.24 mm and the PWOV is 74.6% +/- 7.5%. CDI has moderate correlations with
      wall thickness (r=-0.531, P<0.001) and with PWOV (R=-0.435, P<0.001).
      CONCLUSIONS: Detected with coronary MR imaging, CDI is quantitatively correlated
      with the morphological features of the coronary artery in HTx patients. Coronary
      stiffness has the potential to become an alternative imaging biomarker for the
      quantitative assessment of the status of cardiac allografts.

PMID- 24929443
TI  - Clinical values for abnormal 18F-FDG uptake in the head and neck region of
      patients with head and neck squamous cell carcinoma.
AB  - PURPOSE: Fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography
      (PET)/computed tomography (CT) is used to identify index or second primary cancer
      (SP) of the head and neck (HN) through changes in (18)F-FDG uptake. However, both
      physiologic and abnormal lesions increase (18)F-FDG uptake. Therefore, we
      evaluated (18)F-FDG uptake in the HN region to determine clinical values of
      abnormal tracer uptake. METHODS: A prospective study approved by the
      institutional review board was conducted in 314 patients with newly diagnosed HN
      squamous cell carcinoma (HNSCC) and informed consent was obtained from all
      enrolled patients. The patients received initial staging workups including (18)F
      FDG PET/CT and biopsies. All lesions with abnormal HN (18)F-FDG uptake were
      recorded and most of those were confirmed by biopsies. Diagnostic values for
      abnormal (18)F-FDG uptake were calculated. RESULTS: Abnormal (18)F-FDG uptake was
      identified in primary tumors from 285 (91.9%) patients. False-negative results
      were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P<0.001).
      Thirty-eight regions of abnormal (18)F-FDG uptake were identified in 36 (11.5%)
      patients: the thyroid (n=13), maxillary sinus (n=7), palatine tonsil (n=6),
      nasopharynx (n=5), parotid gland (n=2) and others (n=5). Synchronous SP of the HN
      was identified in eight (2.5%) patients: the thyroid (n=5), palatine tonsil
      (n=2), and epiglottis (n=1). The sensitivity and specificity of (18)F-FDG PET/CT
      for identification of SPs were 75.0% and 98.7%, respectively. CONCLUSIONS: (18)F
      FDG PET/CT is a reliable method for tumor staging and identify SP in HN region,
      promoting appropriate therapeutic planning. Additional examinations may be
      required to identify superficial or small-volume tumors.

PMID- 24929444
TI  - Pain management in Guillain-Barre syndrome: a systematic review.
AB  - INTRODUCTION: Pain is a common symptom in patients with Guillain-Barre syndrome.
      Intensity is moderate to severe in most cases and pain may persist after
      resolution of the disease. OBJECTIVE: Identify the most appropriate analgesic
      therapy for pain management in patients with Guillain-Barre syndrome. MATERIAL
      AND METHODS: Systematic review and selection of scientific articles on treatment
      of pain in Guillain-Barre syndrome patients, published between January 1985 and
      December 2012. We included only randomised, double-blind, controlled trials
      assessing the effectiveness of drugs for pain management in these patients.
      RESULTS: Four articles met the inclusion criteria. One evaluated the use of
      gabapentin, another evaluated carbamazepine, a third compared gabapentin to
      carbamazepine, and the last evaluated use of methylprednisolone. Both
      carbamazepine and gabapentin were useful for pain management. Patients
      experienced lower-intensity pain with gabapentin treatment in the study comparing
      that drug to carbamazepine. Methylprednisolone was not shown to be effective for
      reducing pain. The published data did not permit completion of a meta-analysis.
      CONCLUSIONS: There is no robust evidence at present that would point to a single
      treatment option for this disorder. Further clinical studies of larger patient
      samples and with a longer duration are needed to characterise types of pain for
      each patient and measure pain intensity in an objective way.

PMID- 24929445
TI  - A cross-sectional survey of critical care services in Sri Lanka: a lower middle
      income country.
AB  - PURPOSE: To describe the extent and variation of critical care services in Sri
      Lanka as a first step towards the development of a nationwide critical care unit
      (CCU) registry. MATERIALS AND METHODS: A cross-sectional survey was conducted in
      all state CCUs by telephone or by visits to determine administration,
      infrastructure, equipment, staffing, and overall patient outcomes. RESULTS: There
      were 99 CCUs with 2.5 CCU beds per 100000 population and 13 CCU beds per 1 000
      hospital beds. The median number of beds per CCU was 5. The overall admissions
      were 194 per 100000 population per year. The overall bed turnover was 76.5 per
      unit per year, with CCU mortality being 17%. Most CCUs were headed by an
      anesthetist. There were a total of 790 doctors (1.6 per bed), 1,989 nurses (3.9
      per bed), and 626 health care assistants (1.2 per bed). Majority (87.9%) had 1:1
      nurse-to-patient ratio, although few (11.4%) nurses had received formal intensive
      care unit training. All CCUs had basic infrastructure (electricity, running
      water, piped oxygen) and basic equipment (such as electronic monitoring and
      infusion pumps). CONCLUSION: Sri Lanka, a lower middle-income country has an
      extensive network of critical care facilities but with inequalities in its
      distribution and facilities.

PMID- 24929447
TI  - Temporal association of ambient temperature and relative humidity with Spirocerca
      lupi infection of Onthophagus sellatus: a 14-year longitudinal study.
AB  - The parasitic nematode Spirocerca lupi causes major morbidity and mortality in
      dogs. The scarab beetle Onthophagus sellatus is its major intermediate host in
      Israel. We investigated the prevalence of beetle infection by S. lupi in
      different years between 1994 and 2008. The average monthly maximum and minimum
      relative humidity (RH) and ambient temperature (AT) throughout the study period
      were calculated based on daily meteorological data. The infection prevalence
      decreased over the study period, possibly due to a chronological change resulting
      from increased preventive treatment of dogs against S. lupi, or climate change.
      Multivariate analysis was performed for these two hypotheses. Under the first
      hypothesis, chronological change was forced into the model, and environmental
      variables were inserted stepwise. The final model included beetle-collection
      date, minimum RH (RH min) during the month preceding beetle collection, its
      interaction with maximal AT (AT max) during that same month, and the interaction
      of maximal RH (RH max) and AT max, during the month of beetle collection. Under
      the second hypothesis, chronological change was not forced. The final model
      included RH max during the month of beetle collection, average RH (RHave) during
      the month preceding beetle collection, and its interaction with AT max during the
      latter month. The results suggest that under both hypotheses, RH and AT during
      the month preceding beetle collection influence S. lupi's ability to develop and
      survive in O. sellatus, and may be used to predict the risk to dogs of S. lupi
      infection.

PMID- 24929446
TI  - Efficacy of free and nanoencapsulated Eucalyptus citriodora essential oils on
      sheep gastrointestinal nematodes and toxicity for mice.
AB  - Herbal medicines with anthelmintic effects are alternatives for the sustainable
      control and prevention of disease caused by gastrointestinal parasites. The
      nanoencapsulation of essential oils has been proposed to enhance the absorption
      of their constituents and improve their efficacy. The present study aimed to
      evaluate the efficacy of free and nanoencapsulated Eucalyptus citriodora
      essential oil (EcEO) on the control of gastrointestinal nematodes of small
      ruminants in vitro and in vivo. Chitosan was used as a matrix for the formulation
      of a nanoemulsion. Chromatographic and physico-chemical analyses of EcEO were
      performed. Egg hatch (EHT) and larval development (LDT) tests were conducted to
      evaluate the effectiveness of nanoencapsulated and free EcEO on the eggs and
      larvae of Haemonchus contortus. Acute toxicity of free and nanoencapsulated EcEO
      was evaluated using mice. Finally, nanoencapsulated EcEO efficacy on the control
      of gastrointestinal nematodes was calculated by fecal egg count reduction test
      (FECRT) treating 30 sheep naturally infected with 250 mg/kg of free and
      nanoencapsulated EcEO. In vitro tests were analyzed by an analysis of variance
      (ANOVA) followed by comparison with the Tukey test. The efficacy of FECRT was
      calculated by the BootStreet program through arithmetic average, using the
      formula 100 (1-XT/XC). To compare the differences between epg, the data were
      transformed to log(x+1) and subjected to an ANOVA to compare the significant
      differences between groups by Tukey's. The level of significance was P<0.05. The
      free (4 mg/ml concentration) and nanoencapsulated (2mg/ml concentration) EcEO
      inhibited larvae hatching by 97.2% and 92.8%, respectively. Free and
      nanoencapsulated EcEO at 8 mg/ml inhibited larval development by 99.8% and 98.1%,
      respectively. In the acute toxicity test, the LD10 and LD50 of free EcEO was 1999
      and 2653 mg/kg, respectively, while the LD10 and LD50 of nanoencapsulated EcEO
      was 1121 and 1681 mg/kg, respectively. Nanoencapsulated and free EcEO reduced FEC
      similarly by 40.5% and 55.9%, respectively at 10 days post-treatment.
      Nanoencapsulated EcEO did not obtain the expected efficacy in vivo.

PMID- 24929448
TI  - Effects of daily pyrantel tartrate on strongylid population dynamics and
      performance parameters of young horses repeatedly infected with cyathostomins and
      Strongylus vulgaris.
AB  - Strongylid infections are ubiquitous in grazing horse populations. Infections
      with cyathostomin (small strongyle) and strongylin (large strongyle) nematodes
      have long been associated with clinical disease in horses, but little is known
      about their subclinical impact. A masked, randomized, controlled study was
      conducted to evaluate the effects of daily administration of pyrantel tartrate on
      body condition scores, weight gain, fecal egg counts, and total worm counts of
      young horses repeatedly inoculated with strongylid larvae. Twenty eight immature
      horses were treated with larvicidal anthelmintic regimens and randomly allocated
      to two groups. Group 1 horses were given a pelleted placebo product once daily,
      and those in Group 2 received pyrantel tartrate once daily at ~ 2.64 mg/kg body
      weight. On five days during each week, ~ 5000 infective cyathostomin larvae were
      administered to each horse. In addition, horses received ~ 25 infective
      Strongylus vulgaris larvae once weekly. Horses were maintained on pasture for 154
      days and had ad libitum access to grass hay throughout. At approximate, 14-day
      intervals, body weights were measured, body condition scores were assigned, fecal
      samples were collected for egg counts, and blood samples were collected for
      measurement of S. vulgaris antibodies and various physiologic parameters. After
      22 weeks at pasture and 14-17 days in confinement, horses were euthanatized and
      necropsied. Nematodes were recovered and counted from aliquots of organ contents,
      representative samples of large intestinal mucosa, and the root of the cranial
      mesenteric artery. Daily treatment with pyrantel tartrate at the recommended
      dosage significantly reduced numbers of adult cyathostomins in the gut lumen and
      early third-stage larvae in the cecal mucosa, increased the proportions of fourth
      stage larvae in the gut contents, and was accompanied by significant improvements
      in body condition scores. Fecal egg counts of horses receiving daily pyrantel
      tartrate were significantly reduced, with percentages of efficacy ranging from
      84.4% to 98.9%, but egg counts of both groups increased significantly over the
      course of the study. Treatment also significantly reduced the numbers of S.
      vulgaris larvae in the cranial mesenteric artery by 99.2%. Serum antibodies to S.
      vulgaris apparently persisted from pre-enrollment infections, but ELISA values
      gradually declined over the course of the study. This study has provided useful
      insights into the effects of daily pyrantel tartrate on the dynamics of
      cyathostomin infection, and into some subclinical effects of strongylid
      parasitism in horses.

PMID- 24929450
TI  - Ending sexual violence in conflict and beyond.

PMID- 24929449
TI  - Molecular characterization, gene structure and antibacterial activity of a g-type
      lysozyme from the European sea bass (Dicentrarchus labrax L.).
AB  - In fish, the first line of defense is represented by the innate immune system and
      the lysozyme is one of the molecules involved in this mechanism of protection.
      Three types of lysozymes have been identified in metazoan, the c-type (chicken or
      conventional), the g-type (goose-type) and the i-type (invertebrate type). They
      are all involved in the hydrolysation of the bacterial cell wall. Our work has
      been focused on the molecular characterization, expression analysis by real-time
      PCR, both at basal condition and after in vivo challenges, and 3D structural
      studies on the g-type lysozyme from sea bass (Dicentrarchus labrax L.). Moreover,
      a recombinant sea bass lysozyme has been produced in Escherichia coli and used to
      investigate the activity of the enzyme at different pH and temperatures and to
      perform antibacterial assays against typical fish pathogens. The cloned sea bass
      cDNA for g-type lysozyme (accession number FN667957) consists of 742 bp and
      translates for a putative protein of 188 amino acids. The molecular weight is
      20.251, 41Da with a theoretical pI of 8.53, two cysteine residues along the
      sequence and no putative signal peptide. These features of the enzyme are in
      agreement with the expected characteristics of a proper g-type lysozyme, except
      for the cysteine residues that in fish are quite variable in number. An alignment
      between known g-type lysozyme sequences evidences that the amino acid residues
      thought to be involved in the enzyme catalysis (Glu(71), Asp(84) and Asp(95) in
      sea bass) are quite well conserved between mammalian, avian and fish sequences.
      The sea bass g-type lysozyme gene is composed of four exons and three introns and
      this gene structure is more compact compared to other known fish lysozyme
      homologues. Modeling of 3D structure has been performed on the template structure
      of g-type lysozyme from Atlantic cod. The catalytic site appears well conserved
      when compared with known structures of fish g-type lysozymes (cod and salmon).
      The basal expression of lysozyme transcripts is highest in gills, followed by
      head kidney and peripheral blood leukocytes. The lysozyme expression is up
      regulated in head kidney leukocytes both after challenge with the fish bacterial
      pathogen Photobacterium damselae subsp. piscicida. The lytic activity, determined
      using as substrate Micrococcus lysodeikticus, was optimal at pH 5.5 and at a
      temperature of 30 degrees C. In conclusion, these results suggest that the
      identified g-type lysozyme should be involved in the innate immune responses of
      sea bass.

PMID- 24929451
TI  - Why is UK performance in child and youth mortality so poor?

PMID- 24929452
TI  - Deaths in young people aged 0-24 years in the UK compared with the EU15+
      countries, 1970-2008: analysis of the WHO Mortality Database.
AB  - BACKGROUND: Concern is growing that mortality and health in children and young
      people in the UK lags behind that of similar countries. METHODS: We analysed
      death registry data provided to the WHO Mortality Database to compare UK
      mortality for children and young people aged 0-24 years with that of European
      Union member states (before May, 2004, excluding the UK, plus Australia, Canada,
      and Norway [the EU15+ countries]) from 1970 to 2008 using the WHO World Mortality
      Database. We grouped causes of death by Global Burden of Disease classification:
      communicable, nutritional, or maternal causes; non-communicable disorders; and
      injury. UK mortality trends were compared with quartiles of mortality in EU15+
      countries. We used quasi-likelihood Poisson models to explore differences between
      intercepts and slopes between the UK and the EU15+ countries. FINDINGS: In 1970,
      UK total mortality was in the best EU15+ quartile (<25th centile) for children
      and young people aged 1-24 years, with UK infant mortality similar to the EU15+
      median. Subsequent mortality reductions in the UK were smaller than were those in
      the EU15+ countries in all age groups. By 2008, total mortality for neonates,
      infants, and children aged 1-4 years in the UK was in the worst EU15+ quartile
      (>75th centile). In 2008, UK annual excess mortality compared with the EU15+
      median was 1035 deaths for infants and 134 for children aged 1-9 years. Mortality
      from non-communicable diseases in the UK fell from being roughly equivalent to
      the EU15+ median in 1970 to the worst quartile in all age groups by 2008, with
      446 annual excess deaths from non-communicable diseases in the UK (280 for young
      people aged 10-24 years) in 2008. UK mortality from injury remained in the best
      EU15+ quartile for the study period in all age groups. INTERPRETATION: The UK has
      not matched the gains made in child, adolescent, and young adult mortality by
      other comparable countries in the 40 years since 1970, particularly for infant
      deaths and mortality from non-communicable diseases, including neuropsychiatric
      disorders. The UK needs to identify and address amenable social determinants and
      health system factors that lead to poor health outcomes for infants and for
      children and young people with chronic disorders. FUNDING: None.

PMID- 24929453
TI  - The PI3K/Akt signalling pathway may play an internal role related to abnormal
      condylar growth: a preliminary study.
AB  - Developmental deformity of the mandible is one of the most common craniofacial
      malformations and is closely related to abnormal condylar growth. In this study,
      the role of PI3K/Akt signalling in the regulation of chondrocyte proliferation
      and hypertrophic differentiation in the condylar cartilage was studied.
      Immunohistochemical staining was used to investigate the expression of PI3K and p
      Akt in the rat condyle cartilage. Rat condylar chondrocytes were cultured for the
      investigation of chondrocyte proliferation and hypertrophic differentiation when
      PI3K/Akt was inhibited. In addition, organ culture of the rat mandibular condyle
      was performed to evaluate the condyle cartilage growth while PI3K/Akt was
      inhibited. PI3K-positive cells and p-Akt-positive cells showing cytoplasmic
      staining were found to be present in the condylar cartilage. Reduced cell
      proliferation was observed in the culture of rat condylar chondrocytes when
      PI3K/Akt was inhibited; however, the hypertrophic differentiation level was
      increased. The proliferative zone thickness of condylar cartilage in the
      experimental group was less than that in the control group (P=0.00185), but the
      hypertrophic zone was greater than that in the control group (P=0.01048).
      PI3K/Akt signalling exerts opposite influences on chondrocyte proliferation and
      hypertrophic differentiation of the condylar cartilage, and these data suggest
      that PI3K/Akt is a potential intracellular regulation signal pathway in condylar
      cartilage development. 

PMID- 24929454
TI  - Neurobiological mechanisms of acupuncture for some common illnesses: a
      clinician's perspective.
AB  - This paper presents some previously proposed neurobiological mechanisms on how
      acupuncture may work in some clinical applications from a clinician's
      perspective. For the treatment of musculoskeletal conditions, the proposed
      mechanisms included microinjury, increased local blood flow, facilitated healing,
      and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby
      affecting the gastric and cardiovascular functions. Acupuncture may also change
      the levels of neurotransmitters such as serotonin and dopamine, thereby affecting
      the emotional state and craving. This mechanism may form the basis for the
      treatment of smoking cessation. By affecting other pain-modulating
      neurotransmitters such as met-enkephalin and substance P along the nociceptive
      pathway, acupuncture may relieve headache. Acupuncture may affect the
      hypothalamus pituitary axis and reduce the release of the luteinizing hormone in
      the treatment of polycystic ovary syndrome. In addition, two other approaches to
      the acupuncture mechanism, the fascia connective tissue network and the primo
      vascular system, are briefly reviewed. Finally, the idea of true versus sham
      acupuncture points, which are commonly used in clinical trials, is examined
      because the difference between true and sham points does not exist in the
      neurobiological model. 

PMID- 24929455
TI  - Efficacy of acupuncture versus local methylprednisolone acetate injection in De
      Quervain's tenosynovitis: a randomized controlled trial.
AB  - There is no consensus on the management of De Quervain's tenosynovitis, but local
      corticosteroid injection is considered the mainstay of treatment. However, some
      patients are reluctant to take steroid injections. This study was performed to
      compare the efficacy of acupuncture versus corticosteroid injection for the
      treatment of this disease. Thirty patients were consequently treated in two
      groups. The acupuncture group received five acupuncture sessions of 30 minutes
      duration on classic points of LI-5, LU-7, and LU-9 and on ahshi points. The
      injection group received one methylprednisolone acetate injection in the first
      dorsal compartment of the wrist. The degree of disability and pain was evaluated
      by using the Quick Disabilities of the Arm, Shoulder, and Hand (Q-DASH) scale and
      the Visual Analogue Scale (VAS) at baseline and at 2 weeks and 6 weeks after the
      start of treatment. The baseline means of the Q-DASH and the VAS scores were 62.8
      and 6.9, respectively. At the last follow-up, the mean Q-DASH scores were 9.8
      versus 6.2 in the acupuncture and injection groups, respectively, and the mean
      VAS scores were 2 versus 1.2. We demonstrated short-term improvement of pain and
      function in both groups. Although the success rate was somewhat higher with
      corticosteroid injection, acupuncture can be considered as an alternative option
      for treatment of De Quervain's tenosynovitis. 

PMID- 24929456
TI  - Use of pupil size to determine the effect of electromagnetic acupuncture on
      activation level of the autonomic nervous system.
AB  - Magnetic fields are widely considered as a method of treatment to increase the
      therapeutic effect when applied to acupoints. Hence, this study proposes a new
      method which creates significant stimulation of acupoints by using weak magnetic
      fields. We conducted this experiment in order to confirm the effect on the
      activation level of the autonomic nervous system by measuring pupil sizes in
      cases of stimulation by using manual acupuncture and electromagnetic acupuncture
      (EMA) at BL15. We selected 30 Hz of biphasic wave form with 570.1 Gauss. To
      confirm the biopotential by the magnetic flux density occurring in EMA that
      affected the activation of the autonomic nervous system, we observed the
      biopotential induced at the upper and the mid left and right trapezius. We
      observed a significant decrease in pupil size only in the EMA group (p < 0.05),
      thus confirming that EMA decreased the pupil size through activation of the
      parasympathetic nerve in the autonomic nervous system. Moreover, we confirmed
      that the amplitude of the biopotential which was caused by 570.1 Gauss was higher
      than +/-20 MUA. Thus, we can conclude that EMA treatment successfully activates
      the parasympathetic nerve in the autonomic nervous system by inducing a
      biotransformation by the induced biopotential.

PMID- 24929457
TI  - The effect of short-term bed-rest on radial pulse in healthy subjects.
AB  - The objective of this study is to investigate the effects of short-term bed rest
      on the radial pulse in healthy subjects. Twenty-one healthy volunteers
      participated in this study. Their radial pulse was measured at different
      measuring positions using a multi-step tonometry system. The participants took 30
      minutes of bed rest and their radial pulse was measured before and after the bed
      rest. The effects of bed rest on the radial pulse were analyzed. The pulse area,
      the amplitudes of h4 and h5, the pulse period, and the diastolic pulse proportion
      increased with short-term bed rest, whereas the proportions of systolic and
      hightension pulse and the fundamental frequency of the pulse wave decreased with
      short-term bed rest. All the changes were in the same direction in both male and
      female participants at all measuring positions; however, some parameters changed
      more in women than in men, and some changed more at the distal position than at
      the proximal position. In shortly, Short-term bed rest induces significant
      changes in the radial pulse of healthy subjects. The results of this study could
      be used as a control reference for clinical acupuncture studies with participants
      lying on a bed for acupuncture treatment. 

PMID- 24929458
TI  - Strong anticancer potential of nano-triterpenoid from Phytolacca decandra against
      A549 adenocarcinoma via a Ca(2+)-dependent mitochondrial apoptotic pathway.
AB  - We isolated a triterpenoid from an ethanolic extract of Phytolacca decandra and
      nanoencapsulated it with biodegradable nontoxic polymers of poly(lactide-co
      glycolide) to examine if the nanoform of this hitherto unexplored betulinic-acid
      derivative (NdBA) could produce a stronger anticancer effect by rendering better
      drug bioavailability and targeted delivery than the nonencapsulated betulinic
      acid derivative (dBA). The nanoparticles were characterized with the help of
      physicochemical and morphological studies involving dynamic light scattering and
      atomic force microscopy. A549 cancer cells were exposed to NdBA and dBA at the
      IC50 doses of 50 MUg/mL and 100 MUg/mL, respectively. Mitochondrial dysfunction
      mediated apoptosis was determined by examining the changes in the intracellular
      calcium content, the reactive oxygen species accumulation, the cytochrome c
      release, the upregulation of Bcl-2-associated-X protein (Bax) and caspase 3, the
      downregulation of B cell lymphoma 2, and the mitochondrial membrane potential
      (DeltaPsim) depolarization. Apoptosis was also verified by acridine orange
      staining observed under fluorescence microscopy and annexin V-fluorescein
      isothiocyanate/propidium iodide staining through flow cytometric studies. The
      levels of intracellular adenosine triphosphate/adenosine diphosphate ratio
      decreased, and the ATPase activity increased more strikingly in A549 cells
      exposed to NdBA than in A549 cells exposed to dBA. Overall results showed that
      both drugs directly target the mitochondrial oxidative phosphorylation system,
      with NdBA having a stronger effect, indicating NdBA to be a better candidate for
      the development of an anticancer drug for use against lung adenocarcinomas.

PMID- 24929459
TI  - Increase in plasma phylloquinone concentrations following acupoint injection for
      the treatment of primary dysmenorrhea.
AB  - The therapeutic benefits of acupoint injection of vitamin K in spleen-6 (SP6) for
      the treatment of primary dysmenorrhea have been observed in limited clinical
      settings. However, menadione, the form of vitamin K most studied for treating
      dysmenorrhea, is not routinely used in clinical practice in North America. As
      part of a larger clinical trial among women aged 18-25 years with primary
      dysmenorrhea, we conducted a substudy to test the plasma concentration of
      phylloquinone (vitamin K1). We collected blood samples from four women before and
      24-48 hours after an acupoint injection of phylloquinone in SP6. Despite the
      rapid turnover of phylloquinone observed in previous studies, we found that the
      plasma phylloquinone concentrations increased significantly from preinjection to
      1-2 days after the injection. Interestingly, higher phylloquinone concentrations
      were correlated with less pain intensity among women with dysmenorrhea.
      Additional research is needed to understand the association between vitamin K and
      menstrual pain, including the role of vitamin K deficiency in inflammation and
      pain, and on the possible mechanisms of acupoint injection of vitamin K for the
      treatment of primary dysmenorrhea. 

PMID- 24929460
TI  - Complex regional pain syndrome type 1 relieved by acupuncture point injections
      with placental extract.
AB  - This is a case report of a female patient who developed complex regional pain
      syndrome in the left upper limb after a traumatic injury to the distal part of
      the left forearm. The pain was immediate and resistant to oral analgesics and
      continued transcutaneous electrical nerve stimulation. Five months after the
      injury, the patient presented to our clinic with severe pain, swelling, redness,
      cold sensation of the left hand, and loss of function from the left hand up to
      the left shoulder. Acupuncture points LI5, LU2, SI10, HT1, GB21, and SI11 (which
      are localized in the joints or in the muscles responsible for the movement of the
      left upper limb) were selected for the application of the placental extract.
      Injection of placental extract into the acupuncture points resulted in dramatic
      pain relief, swelling remission, motor recovery, temperature normalization, and
      disappearance of redness in this patient with complex regional pain syndrome type
      1. 

PMID- 24929461
TI  - Protocol: the effect of 12 weeks of Tai Chi practice on anxiety in healthy but
      stressed people compared to exercise and wait-list comparison groups: a
      randomized controlled trial.
AB  - Stress is a major problem in today's fast-paced society and can lead to serious
      psychosomatic complications. The ancient Chinese mind-body exercise of Tai Chi
      may provide an alternative and self-sustaining option to pharmaceutical
      medication for stressed individuals to improve their coping mechanisms. The
      protocol of this study is designed to evaluate whether Tai Chi practice is
      equivalent to standard exercise and whether the Tai Chi group is superior to a
      wait-list control group in improving stress coping levels. This study is a 6
      week, three-arm, parallel, randomized, clinical trial designed to evaluate Tai
      Chi practice against standard exercise and a Tai Chi group against a nonactive
      control group over a period of 6 weeks with a 6-week follow-up. A total of 72
      healthy adult participants (aged 18-60 years) who are either Tai Chi naive or
      have not practiced Tai Chi in the past 12 months will be randomized into a Tai
      Chi group (n = 24), an exercise group (n = 24) or a wait-list group (n = 24). The
      primary outcome measure will be the State Trait Anxiety Inventory with secondary
      outcome measures being the Perceived Stress Scale 14, heart rate variability,
      blood pressure, Short Form 36 and a visual analog scale. The protocol is reported
      using the appropriate Standard Protocol Items: Recommendations for Interventional
      Trials (SPIRIT) items.

PMID- 24929462
TI  - Major controversies in Fluency disorders: clarifying the relationship between
      anxiety and stuttering.

PMID- 24929463
TI  - Stuttering in relation to anxiety, temperament, and personality: review and
      analysis with focus on causality.
AB  - Anxiety and emotional reactions have a central role in many theories of
      stuttering, for example that persons who stutter would tend to have an
      emotionally sensitive temperament. The possible relation between stuttering and
      certain traits of temperament or personality were reviewed and analyzed, with
      focus on temporal relations (i.e., what comes first). It was consistently found
      that preschool children who stutter (as a group) do not show any tendencies
      toward elevated temperamental traits of shyness or social anxiety compared with
      children who do not stutter. Significant group differences were, however,
      repeatedly reported for traits associated with inattention and
      hyperactivity/impulsivity, which is likely to reflect a subgroup of children who
      stutter. Available data is not consistent with the proposal that the risk for
      persistent stuttering is increased by an emotionally reactive temperament in
      children who stutter. Speech-related social anxiety develops in many cases of
      stuttering, before adulthood. Reduction of social anxiety in adults who stutter
      does not in itself appear to result in significant improvement of speech fluency.
      Studies have not revealed any relation between the severity of the motor symptoms
      of stuttering and temperamental traits. It is proposed that situational
      variability of stuttering, related to social complexity, is an effect of
      interference from social cognition and not directly from the emotions of social
      anxiety. In summary, the studies in this review provide strong evidence that
      persons who stutter are not characterized by constitutional traits of anxiety or
      similar constructs. EDUCATIONAL OBJECTIVES: This paper provides a review and
      analysis of studies of anxiety, temperament, and personality, organized with the
      objective to clarify cause and effect relations. Readers will be able to (a)
      understand the importance of effect size and distribution of data for
      interpretation of group differences; (b) understand the role of temporal
      relations for interpretation of cause and effect; (c) discuss the results of
      studies of anxiety, temperament and personality in relation to stuttering; and
      (d) discuss situational variations of stuttering and the possible role of social
      cognition.

PMID- 24929464
TI  - Anxiety of children and adolescents who stutter: a review.
AB  - PURPOSE: Adults who stutter have heightened rates of anxiety disorders,
      particularly social anxiety disorder, compared with non-stuttering controls.
      However, the timing of anxiety onset and its development in relation to
      stuttering is poorly understood. Identifying the typical age of anxiety onset in
      stuttering has significant clinical implications and is crucial for the
      management of both disorders across the lifespan. The present review aims to
      determine the scope of the research pertaining to this topic, identify trends in
      findings, and delineate timing of anxiety onset in stuttering. METHODS: We
      examine putative risk factors of anxiety present for children and adolescents who
      stutter, and provide a review of the research evidence relating to anxiety for
      this population. RESULTS: Young people who stutter can experience negative social
      consequences and negative attitudes towards communication, which is hypothesised
      to place them at increased risk of developing anxiety. The prevalence of anxiety
      of young people who stutter, and the timing of anxiety onset in stuttering could
      not be determined. This was due to methodological limitations in the reviewed
      research such as small participant numbers, and the use of measures that lack
      sensitivity to identify anxiety in the targeted population. CONCLUSIONS: In sum,
      the evidence suggests that anxiety in stuttering might increase over time until
      it exceeds normal limits in adolescence and adulthood. The clinical implications
      of these findings, and recommendations for future research, are discussed.
      EDUCATIONAL OBJECTIVES: The reader will be able to: (a) discuss contemporary
      thinking on the role of anxiety in stuttering and reasons for this view; (b)
      describe risk factors for the development of anxiety in stuttering, experienced
      by children and adolescents who stutter (c) outline trends in current research on
      anxiety and children and adolescents with stuttering; and (d) summarise
      rationales behind recommendations for future research in this area.

PMID- 24929465
TI  - Trait and social anxiety in adults with chronic stuttering: conclusions following
      meta-analysis.
AB  - PURPOSE: The relationship between chronic stuttering and anxiety has been a
      matter of some debate over the past two decades, with a major emphasis of
      research focused on examining whether people who stutter have abnormally elevated
      levels of trait or social anxiety. The major goal of this paper was to perform a
      systematic literature review and perform meta-analyses on research that has
      assessed (i) trait anxiety and (ii) social anxiety, in adults who stutter.
      METHOD: Only studies that met strict inclusion criteria were selected for the
      meta-analyses. Two meta-analyses were conducted, the first for trait anxiety, and
      the second for social anxiety. Meta-analysis combines statistically the results
      of selected studies that meet strict design criteria, thereby clarifying the size
      of differences in trait and social anxiety between adults who stutter and adults
      who do not stutter. RESULTS: Meta-analytic results confirmed that adults with
      chronic stuttering do have substantially elevated trait and social anxiety. The
      overall effect size for trait and social anxiety was calculated to be .57 and
      .82, respectively. CONCLUSIONS: Trait and social anxiety are definite problems
      for many adults who stutter. Clinical implications of these findings for the
      diagnosis and treatment of adult who stutter are discussed. EDUCATIONAL
      OBJECTIVES: The reader will be able to: (a) describe the process of conducting a
      systematic review and meta-analysis; (b) describe the possible impact of
      publication bias on meta-analysis results; (c) explain the impact of a chronic
      disorder like stuttering on levels of trait anxiety; (d) explain the impact of
      stuttering on levels of social anxiety; (e) interpret the results of meta
      analysis when applied to differences in anxiety between adult people who stutter
      and those who do not stutter; and (f) describe implications for fluency enhancing
      treatments.

PMID- 24929466
TI  - Anxiety and speaking in people who stutter: an investigation using the emotional
      Stroop task.
AB  - People with anxiety disorders show an attentional bias towards threat or negative
      emotion words. This exploratory study examined whether people who stutter (PWS),
      who can be anxious when speaking, show similar bias and whether reactions to
      threat words also influence speech motor planning and execution. Comparisons were
      made between 31 PWS and 31 fluent controls in a modified emotional Stroop task
      where, depending on a visual cue, participants named the colour of threat and
      neutral words at either a normal or fast articulation rate. In a manual version
      of the same task participants pressed the corresponding colour button with either
      a long or short duration. PWS but not controls were slower to respond to threat
      words than neutral words, however, this emotionality effect was only evident for
      verbal responding. Emotionality did not interact with speech rate, but the size
      of the emotionality effect among PWS did correlate with frequency of stuttering.
      Results suggest PWS show an attentional bias to threat words similar to that
      found in people with anxiety disorder. In addition, this bias appears to be
      contingent on engaging the speech production system as a response modality. No
      evidence was found to indicate that emotional reactivity during the Stroop task
      constrains or destabilises, perhaps via arousal mechanisms, speech motor
      adjustment or execution for PWS. EDUCATIONAL OBJECTIVES: The reader will be able
      to: (1) explain the importance of cognitive aspects of anxiety, such as
      attentional biases, in the possible cause and/or maintenance of anxiety in people
      who stutter, (2) explain how the emotional Stroop task can be used as a measure
      of attentional bias to threat information, and (3) evaluate the findings with
      respect to the relationship between attentional bias to threat information and
      speech production in people who stutter.

PMID- 24929467
TI  - Axis I anxiety and mental health disorders among stuttering adolescents.
AB  - PURPOSE: The purpose of this study was to evaluate anxiety and psychological
      functioning among adolescents seeking speech therapy for stuttering using a
      structured, diagnostic interview and psychological questionnaires. This study
      also sought to determine whether any differences in psychological status were
      evident between younger and older adolescents. METHOD: Participants were 37
      stuttering adolescents seeking stuttering treatment. We administered the
      Computerized Voice Version of the Diagnostic Interview Schedule for Children, and
      five psychometric tests. Participants were classified into younger (12-14 years;
      n=20) and older adolescents (15-17 years; n=17). RESULTS: Thirty-eight percent of
      participants attained at least one diagnosis of a mental disorder, according to
      the diagnostic criteria of the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV; APA, 2000), with the majority of these
      diagnoses involving anxiety. This figure is double current estimates for general
      adolescent populations, and is consistent with our finding of moderate and
      moderate-severe quality of life impairment. Although many of the scores on
      psychological measures fell within the normal range, older adolescents (15-17
      years) reported significantly higher anxiety, depression, reactions to
      stuttering, and emotional/behavioral problems, than younger adolescents (12-14
      years). There was scant evidence that self-reported stuttering severity is
      correlated with mental health issues. There are good reasons to believe these
      results are conservative because many participants gave socially desirable
      responses about their mental health status. DISCUSSION: These results reveal a
      need for large-scale, statistically powerful assessments of anxiety and other
      mental disorders among stuttering adolescents with reference to control
      populations. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) explain the
      clinical importance of assessing for mental health with stuttering adolescents,
      (b) state the superior method for adolescent mental health assessment and (c)
      state a major issue with determining the genuineness of stuttering adolescent
      responses to psychological assessment.

PMID- 24929468
TI  - Social anxiety disorder and stuttering: current status and future directions.
AB  - Anxiety is one of the most widely observed and extensively studied psychological
      concomitants of stuttering. Research conducted prior to the turn of the century
      produced evidence of heightened anxiety in people who stutter, yet findings were
      inconsistent and ambiguous. Failure to detect a clear and systematic relationship
      between anxiety and stuttering was attributed to methodological flaws, including
      use of small sample sizes and unidimensional measures of anxiety. More recent
      research, however, has generated far less equivocal findings when using social
      anxiety questionnaires and psychiatric diagnostic assessments in larger samples
      of people who stutter. In particular, a growing body of research has demonstrated
      an alarmingly high rate of social anxiety disorder among adults who stutter.
      Social anxiety disorder is a prevalent and chronic anxiety disorder characterised
      by significant fear of humiliation, embarrassment, and negative evaluation in
      social or performance-based situations. In light of the debilitating nature of
      social anxiety disorder, and the impact of stuttering on quality of life and
      personal functioning, collaboration between speech pathologists and psychologists
      is required to develop and implement comprehensive assessment and treatment
      programmes for social anxiety among people who stutter. This comprehensive
      approach has the potential to improve quality of life and engagement in everyday
      activities for people who stutter. Determining the prevalence of social anxiety
      disorder among children and adolescents who stutter is a critical line of future
      research. Further studies are also required to confirm the efficacy of Cognitive
      Behaviour Therapy in treating social anxiety disorder in stuttering. EDUCATIONAL
      OBJECTIVES: The reader will be able to: (a) describe the nature and course of
      social anxiety disorder; (b) outline previous research regarding anxiety and
      stuttering, including features of social anxiety disorder; (c) summarise research
      findings regarding the diagnostic assessment of social anxiety disorder among
      people who stutter; (d) describe approaches for the assessment and treatment of
      social anxiety in stuttering, including the efficacy of Cognitive Behaviour
      Therapy; and (e) outline clinical implications and future directions associated
      with heightened social anxiety in stuttering.

PMID- 24929469
TI  - Social support and its association with negative affect in adults who stutter.
AB  - PURPOSE: The purpose of the research reported in this manuscript is to clarify
      the relationship between social support and negative affect for people who
      stutter. Social support results in many benefits that help individuals to achieve
      self-esteem, motivation to adjust adaptively, and to experience a sense of
      belonging. Lack of such support is likely to result in heightened anxiety and
      negative affect manifesting in many forms. METHOD: This study used the Symptom
      Checklist--Revised (SCL-90-R) and the Significant Others Scale (SOS) to
      investigate social support and its relationship to negative affect in 200 adults
      who stutter, with comparisons made to 200 adults who do not stutter. Negative
      affect was assessed by interpersonal sensitivity, depressive mood and anxiety.
      The Significant Others Scale was used to provide an indication of the
      participants' actual and ideal levels of social support. RESULTS: It was found
      that (i) those participants who stuttered had significantly elevated levels of
      negative affect across the SCL-90-R domains of interpersonal sensitivity,
      depressive mood and anxiety; (ii) the group who stuttered was found to have lower
      levels of actual and ideal social support; and (iii) those who stuttered and who
      also had low social support had significantly elevated levels of negative affect.
      CONCLUSION: Results highlight the potentially harmful influence that poor social
      support has on mood states for adults who stutter. These findings have
      implications for treatment such as the necessity to address and integrate social
      support and social integration issues in the treatment process for adults who
      stutter. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) describe the
      methodology of assessing social support using the Social Support Scale (SOS); (b)
      apply the concept of assessing social support in stuttering to treatment; (c)
      describe the protective contribution of helpful social support for adults who
      stutter; (d) describe the relationship between social support and negative mood
      states.

PMID- 24929470
TI  - The impact of threat and cognitive stress on speech motor control in people who
      stutter.
AB  - PURPOSE: In the present study, an Emotional Stroop and Classical Stroop task were
      used to separate the effect of threat content and cognitive stress from the
      phonetic features of words on motor preparation and execution processes. METHOD:
      A group of 10 people who stutter (PWS) and 10 matched people who do not stutter
      (PNS) repeated colour names for threat content words and neutral words, as well
      as for traditional Stroop stimuli. Data collection included speech acoustics and
      movement data from upper lip and lower lip using 3D EMA. RESULTS: PWS in both
      tasks were slower to respond and showed smaller upper lip movement ranges than
      PNS. For the Emotional Stroop task only, PWS were found to show larger inter-lip
      phase differences compared to PNS. General threat words were executed with faster
      lower lip movements (larger range and shorter duration) in both groups, but only
      PWS showed a change in upper lip movements. For stutter specific threat words,
      both groups showed a more variable lip coordination pattern, but only PWS showed
      a delay in reaction time compared to neutral words. Individual stuttered words
      showed no effects. Both groups showed a classical Stroop interference effect in
      reaction time but no changes in motor variables. CONCLUSION: This study shows
      differential motor responses in PWS compared to controls for specific threat
      words. Cognitive stress was not found to affect stuttering individuals
      differently than controls or that its impact spreads to motor execution
      processes. EDUCATIONAL OBJECTIVES: After reading this article, the reader will be
      able to: (1) discuss the importance of understanding how threat content
      influences speech motor control in people who stutter and non-stuttering
      speakers; (2) discuss the need to use tasks like the Emotional Stroop and Regular
      Stroop to separate phonetic (word-bound) based impact on fluency from other
      factors in people who stutter; and (3) describe the role of anxiety and cognitive
      stress on speech motor processes.

PMID- 24929471
TI  - Tributes for Gene J. Brutten, Ph.D. (1928-2013).

PMID- 24929472
TI  - Effect of ferrocene-substituted porphyrin RL-91 on Candida albicans biofilm
      formation.
AB  - Ferrocene-substituted porphyrin RL-91 exhibits antifungal activity against
      opportune human pathogen Candida albicans. RL-91 efficiently inhibits growth of
      both planktonic C. albicans cells and cells within biofilms without
      photoactivation. The minimal inhibitory concentration for plankton form (PMIC)
      was established to be 100 MUg/mL and the same concentration killed 80% of sessile
      cells in the mature biofilm (SMIC80). Furthermore PMIC of RL-91 efficiently
      prevents C. albicans biofilm formation. RL-91 is cytotoxic for human fibroblasts
      in vitro in concentration of 10 MUg/mL, however it does not cause hemolysis in
      concentrations of up to 50 MUg/mL. These findings open possibility for
      application of RL-91 as an antifungal agent for external antibiofilm treatment of
      medical devices as well as a scaffold for further development of porphyrin based
      systemic antifungals.

PMID- 24929473
TI  - Successful transradial removal of an inflated coronary stent dislodged from the
      right coronary ostium.
AB  - We describe our solution to the unusual situation of an inflated, large coronary
      stent (3.5 mm diameter) which became dislodged from the ostium of the right
      coronary artery after deployment during a transradial procedure. We discussed
      tips for retrieval from the radial artery while preserving the access for
      completion of the procedure. 

PMID- 24929474
TI  - Object and space perception - is it a matter of hemisphere?
AB  - In the 1980s, following Newcombe's observations, Ungerleider and Mishkin put
      forward the functional subdivision of the visual system into a ventral stream
      dedicated to object perception and a dorsal stream dedicated to space perception.
      Ten years after this discovery, the perception-action model re-defined the dorsal
      stream as responsible for non-conscious visual guidance, and most recently a
      tripartition has been suggested to account for a variety of visuospatial
      functions. Here, we investigated the neural underpinnings of object and space
      perception by combining the administration of the Visual Object Space Perception
      (VOSP) battery with a voxel-based lesion symptom mapping (VLSM) approach in a
      large sample of patients with penetrating traumatic brain injury (pTBI). First,
      our results provided new support for the complementary role of both hemispheres
      in object recognition. The right lateral occipital complex was found to be
      critical in early perceptual discrimination, whereas more anterior temporal and
      frontal regions in the left hemisphere were found to be critical in more complex
      forms of object discrimination and recognition. Second, our findings confirmed
      that space perception depended on the integrity of the right inferior parietal
      lobule (IPL) and revealed that a network linking the right IPL with the right
      premotor cortex was critical for the perception of spatial relationships in both
      2D and 3D representations. Taken together, our results supported the functional
      subdivision of the visual system and shed new light on the specific processes
      involved along both the dorsal and the ventral streams. 

PMID- 24929475
TI  - Budget goal commitment, clinical managers' use of budget information and
      performance.
AB  - Despite the importance placed on accounting as a means to influence performance
      in public healthcare, there is still a lot to be learned about the role of
      management accounting in clinical managers' work behavior and their link with
      organizational performance. The article aims at analyzing the motivational role
      of budgetary participation and the intervening role of individuals' mental states
      and behaviors in influencing the relationship between budgetary participation and
      performance. According to the goal-setting theory, SEM technique was used to test
      the relationships among variables. The data were collected by a survey conducted
      in an Italian hospital. The results show that: (i) budgetary participation does
      not directly influence the use of budget information, but the latter is
      encouraged by the level of budget goal commitment which, as a result, is
      influenced by the positive motivational consequences of participative budgeting;
      (ii) budget goal commitment does not directly influence performance, but the
      relationship is mediated by the use of budget information. This study contributes
      to health policy and management accounting literature and has significant policy
      implications. Mainly, the findings prove that the introduction of business-like
      techniques in the healthcare sector can improve performance if attitudinal and
      behavioral variables are adequately stimulated. 

PMID- 24929476
TI  - Environmental risk assessment of selected pharmaceuticals in Turkey.
AB  - In this study, environmental risks of selected pharmaceuticals were investigated
      to assess potential hazards. Ciprofloxacin, Clarithromycin, Cefuroxime axetil,
      antibiotics, Benzalkoniuman antiseptic, Paracetamol, an analgesic, and Naproxen,
      an anti-inflammatory, were selected due to their high rate of usage in Turkey.
      Ciprofloxacin was found to have the highest risk due to its high PEC/PNEC ratio
      (28.636). Benzalkonium, Paracetamol and Clarithromycin have a potential to cause
      environmental hazards. The biodegradation and biological concentration factors
      (BCF) of the drugs were also determined using EPA/STWIN and EPA/BCFWIN programs.
      The results illustrated that these pharmaceuticals are nonbiodegradable in
      wastewater treatment plants. The BCFs of Benzalkonium and Clarithromycin were
      found to be very high, 70.790 L/kg and 56.490 L/kg, respectively. It was
      suggested that alternative treatment methods other than biological ones should be
      investigated for these pharmaceuticals because of their low biodegradability.
      Also, unnecessary use of antibiotics is supposed to be discouraged to reduce
      environmental hazards.

PMID- 24929477
TI  - Effects of agmatine and resveratrol on RGC-5 cell behavior under light
      stimulation.
AB  - A light radiation causes dysfunction and death of retinal cells and leads to
      degeneration. Present study, investigated the light-induced cell dysfunction, and
      their activity. Further, the effects of agmatine and resveratrol on light-induced
      damage and these underlying photo-oxidative and protective mechanisms were
      monitored by real-time bio-impedance system. After light exposure retinal
      ganglion cells underwent death in a time dependent manner. During light exposure
      the cells elevate free radicals and Ca(2+), followed by nitric oxide (NO) and
      tumor necrosis factor-alpha (TNF-alpha), which can be facilitated to cell demise.
      The results revealed that these drugs can control the elevation of free radical,
      calcium gating, NO level, and increased TNF-alpha, which could diminish cell
      photo-damage. In summary, resveratrol helps more to rescue damaged cells compared
      to agmatine. The proposed system suggested mechanism could meet to identify the
      photo-toxic effects in retinal cells, and provides high throughput screening for
      early stages photo-damage. 

PMID- 24929478
TI  - A simultaneous endoscopic and laparoscopic approach for management of early
      iatrogenic bile duct obstruction.
AB  - BACKGROUND: Bile duct occlusion secondary to inadvertent application of a
      surgical clip or suture usually is managed with endoscopic or surgical
      exploration. OBJECTIVE: To evaluate the safety and efficacy of a novel method of
      simultaneous endoscopic and laparoscopic approach in patients with acute
      iatrogenic bile duct obstruction. DESIGN: Single arm study and single center
      design. SETTING: University medical center. PATIENTS: Three consecutive patients
      diagnosed with complete or near-complete obstruction of a bile duct after
      cholecystectomy were identified for inclusion. INTERVENTIONS: Endoscopic
      retrograde cholangiopancreatography (ERCP) and laparoscopy was performed
      simultaneously. Surgeon removes the surgical clips or suture from the bile duct
      with concurrent ERCP by endoscopist to assess and treat bile duct injury
      following resolution of the block. MAIN OUTCOME MEASUREMENTS: Technical and
      clinical success rate and adverse events. RESULTS: All of the patients were seen
      between 5 and 7 days after cholecystectomy. The diagnosis of obstructed bile duct
      was established by ERCP. The guidewire failed to negotiate across the obstruction
      in one of these patients. In another patient, a guidewire could be passed, but a
      biliary stent could not be deployed across the high-grade stricture. In a third
      patient, only a single biliary stent (7F * 11 cm) could be placed across the
      obstruction, with significant difficulty. In all the patients, simultaneous ERCP
      and laparoscopy were performed immediately to remove the surgical clips and/or
      sutures from the bile duct, followed by placement of biliary stents. LIMITATIONS:
      Small series. CONCLUSION: The concurrent endoscopic and laparoscopic approach for
      the management of acute iatrogenic common bile duct obstruction is associated
      with rapid and complete recovery.

PMID- 24929479
TI  - Biliary papillomatosis: diagnosis with direct peroral cholangioscopy.

PMID- 24929481
TI  - Endoscopically identified pseudomelanosis duodeni: striking yet harmless.

PMID- 24929482
TI  - EUS diagnosis and endoscopic management of iatrogenic biliary stent placement
      into the portal vein.

PMID- 24929480
TI  - Neoplasms arising in large gastric hyperplastic polyps: endoscopic and pathologic
      features.
AB  - BACKGROUND: Little is known about gastric neoplasms arising from hyperplastic
      polyps (HPs). OBJECTIVE: To investigate the risk factors associated with
      neoplasms within HPs and to evaluate the role of alterations of the p16-cyclin D1
      pRb pathway in the malignant transformation of HPs. DESIGN: Retrospective, case
      control study. SETTING: Tertiary-care center. PATIENTS: Between May 1995 and
      January 2011, a total of 809 HPs >1 cm were investigated. Associated neoplasms
      were present in 30 HPs (case group); 30 HPs without neoplasms were selected as a
      control group. INTERVENTIONS: Gastric polypectomy. MAIN OUTCOME MEASUREMENTS: The
      risk factors associated with neoplasms within HPs and immunohistochemical
      expression of p16, cyclin D1, p53, and Ki-67 between case and control groups.
      RESULTS: Of the 809 HPs, 15 had associated dysplasia, and 15 had carcinoma.
      Multivariate analysis showed that neoplasm was associated with patient age (odds
      ratio [OR] 1.159; 95% confidence interval [CI], 1.243-2.044; P < .001), polyp
      size (OR 1.103; 95% CI, 1.055-1.152; P < .001), and polyp lobulation (OR 4.549;
      95% CI, 1.759-11.0766; P < .001) but not with location, multiplicity, intestinal
      metaplasia, growth pattern, or Helicobacter pylori infection. Loss of p16
      expression and high Ki-67 expression were observed in dysplastic areas of HPs
      compared with the control group (p16 = 14.3% vs 60%; P = .001, Ki-67 = 60.7% vs
      36.7%; P < .001). However, no significant differences were found in nondysplastic
      areas in both groups. LIMITATIONS: Single-center, retrospective study.
      CONCLUSION: HPs >1 cm may indicate the presence of neoplasms. Loss of p16 and
      high Ki-67 expression may be markers of HP-associated dysplasia.

PMID- 24929483
TI  - A novel balloon colonoscope detects significantly more simulated polyps than a
      standard colonoscope in a colon model.
AB  - BACKGROUND: Although standard colonoscopy is considered the optimal test to
      detect adenomas, it can have a significant adenoma miss rate. A major
      contributing factor to high miss rates is the inability to visualize adenomas
      behind haustral folds and at anatomic flexures. OBJECTIVE: To compare the
      diagnostic yield of balloon-assisted colonoscopy versus standard colonoscopy in
      the detection of simulated polyps in a colon model. DESIGN: Prospective, cohort
      study. SETTING: International gastroenterology meeting. SUBJECT: A colon model
      composed of elastic material, which mimics the flexible structure of haustral
      folds, allowing for dynamic responses to balloon inflation, with embedded
      simulated colon polyps (n = 12 silicone "polyps"). INTERVENTIONS: Fifty
      gastroenterologists were recruited to identify simulated colon polyps in a colon
      model, first using standard colonoscopy immediately followed by balloon-assisted
      colonoscopy. MAIN OUTCOME MEASUREMENTS: Detection of simulated polyps. RESULTS:
      The median polyp detection rate for all simulated polyps was significantly higher
      with balloon-assisted as compared with standard colonoscopy (91.7% vs 45.8%,
      respectively; P < .0001). The significantly higher simulated polyp detection rate
      with balloon-assisted versus standard colonoscopy was notable both for non
      obscured polyps (100.0% vs 75.0%; P < .0001) and obscured polyps (88.0% vs 25.0%;
      P < .0001). LIMITATIONS: Non-randomized design, use of a colon model, and
      simulated colon polyps. CONCLUSION: As compared with standard colonoscopy,
      balloon-assisted colonoscopy detected significantly more obscured and non
      obscured simulated polyps in a colon model. Clinical studies in human
      participants are being pursued to further evaluate this new colonoscopic
      technology.

PMID- 24929485
TI  - EUS-guided transesophageal drainage of a mediastinal abscess using a diabolo
      shaped lumen-apposing metal stent.

PMID- 24929484
TI  - Volatile organic compounds in bile can diagnose malignant biliary strictures in
      the setting of pancreatic cancer: a preliminary observation.
AB  - BACKGROUND: Ascertaining the nature of biliary strictures is challenging. The
      role of volatile organic compounds (VOCs) in bile in determining the cause of
      biliary strictures is not known. OBJECTIVE: To identify potential VOCs in the
      headspaces (gas above the sample) of bile in patients with malignant biliary
      strictures from pancreatic cancer. DESIGN: Prospective cross-sectional study.
      SETTING: Referral center. PATIENTS: Prospective study in which bile was aspirated
      in 96 patients undergoing ERCP for benign and malignant conditions. MAIN OUTCOME
      MEASUREMENTS: Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS
      instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze
      the headspace and to build a predictive model for pancreatic cancer. RESULTS: The
      headspaces from 96 bile samples were analyzed, including 24 from patients with
      pancreatic cancer and 72 from patients with benign biliary conditions. The
      concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide,
      pentane, and trimethylamine [TMA]) were increased in patients with pancreatic
      cancer compared with controls (P < .05). By using receiver-operating
      characteristic curve analysis, we developed a model for the diagnosis of
      pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl
      sulfide, and acetaldehyde. The model [10.94 + 1.8229* log (acetaldehyde) +
      0.7600* log (acetone) - 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) -
      2.1401 * log (trimethylamine) >= 10] identified the patients with pancreatic
      cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9%
      specificity. LIMITATIONS: Sample size. CONCLUSIONS: The measurement of biliary
      fluid VOCs may help to distinguish malignant from benign biliary strictures.
      Further studies are warranted to validate these observations. (Clinical Trial
      Registration Number NCT01565460.).

PMID- 24929486
TI  - Successful management of distal intestinal obstruction syndrome with a jet
      irrigation flushing device during colonoscopy.

PMID- 24929487
TI  - Endoscopic removal of a large common bile duct stone: more than one way to skin a
      cat.

PMID- 24929488
TI  - Buried bumper syndrome: single-step endoscopic management and replacement.

PMID- 24929489
TI  - Prevention of delayed perforation after resection of a massive lateral wall
      duodenal polyp by using an anchored, fully-covered self-expandable metal stent.

PMID- 24929490
TI  - Pancreatic necrosectomy by using a lumen-apposing metal stent.

PMID- 24929491
TI  - Mechanical hemostasis by using the index finger during rectal endoscopic
      submucosal dissection.

PMID- 24929492
TI  - Per-oral endoscopic tunneling for restoration of the esophagus (POETRE).

PMID- 24929493
TI  - Detection and staging of esophageal cancers within Barrett's esophagus is
      improved by assessment in specialized Barrett's units.
AB  - BACKGROUND: Identification and resection of mucosal abnormalities are critical in
      managing dysplastic Barrett's esophagus (BE) because these areas may harbor
      esophageal adenocarcinoma (EAC). OBJECTIVES: To compare mucosal lesion and EAC
      detection rates in dysplastic BE in the community versus a BE unit and assess the
      impact of EMR on disease staging and management. DESIGN: Prospective cohort
      study. SETTING: Tertiary referral center. PATIENTS: Patients with dysplastic BE.
      INTERVENTIONS: Reassessment with high-definition white-light endoscopy (HD-WLE),
      narrow-band imaging (NBI), and Seattle protocol biopsies. EMR performed in
      lesions thought to harbor neoplasia. Review of referral histology and
      endoscopies. MAIN OUTCOME MEASUREMENTS: Mucosal lesion and EAC detection rates in
      a BE unit versus the community. Impact of EMR on management. RESULTS: Sixty-nine
      patients were referred (88% male; median age, 69 years). At referral, HD-WLE/NBI
      use was 57%/14%, and Seattle protocol adherence was 20%. Eighteen patients had
      intramucosal cancer. Lesions were detected in 65 patients in the BE unit versus
      29 patients at referral (P < .001). EMR was performed in 47 patients. BE unit
      assessment confirmed EAC in all 18 patients and identified 10 additional patients
      (56% increased cancer detection, P = .036); all 10 had lesions identified in the
      BE unit (vs 3 identified at referral). EMR in these patients found submucosal
      cancer (n = 4) and intramucosal cancer (n = 6), resulting in esophagectomy (n =
      4) and chemoradiotherapy (n = 1). LIMITATION: Academic center. CONCLUSION: BE
      assessment at a BE unit resulted in increased lesion and EAC detection. EMR of
      early cancers was critical in optimizing patient management. These data suggest
      that BE unit referral be considered in patients with dysplastic BE.

PMID- 24929494
TI  - Adult ileocolic intussusception: endoscopic treatment.

PMID- 24929495
TI  - Endoscopic resection of subtotal and complete circumferential colonic advanced
      mucosal neoplasia.

PMID- 24929496
TI  - Incisionless osteotomy for contouring the skull: pinhole osteo-chipping with
      irrigation for the esthetic treatment of a benign frontal osteoma.

PMID- 24929497
TI  - Herceptin cardiotoxicity and delayed breast reconstruction surgery.

PMID- 24929498
TI  - Dynamics and climate change mitigation potential of soil organic carbon
      sequestration.
AB  - When assessing soil organic carbon (SOC) sequestration and its climate change
      (CC) mitigation potential at global scale, the dynamic nature of soil carbon
      storage and interventions to foster it should be taken into account. Firstly,
      adoption of SOC-sequestration measures will take time, and reasonably such
      schemes could only be implemented gradually at large-scale. Secondly, if soils
      are managed as carbon sinks, then SOC will increase only over a limited time, up
      to the point when a new SOC equilibrium is reached. This paper combines these two
      processes and predicts potential SOC sequestration dynamics in agricultural land
      at global scale and the corresponding CC mitigation potential. Assuming that
      global governments would agree on a worldwide effort to gradually change land use
      practices towards turning agricultural soils into carbon sinks starting 2014, the
      projected 87-year (2014-2100) global SOC sequestration potential of agricultural
      land ranged between 31 and 64 Gt. This is equal to 1.9-3.9% of the SRES-A2
      projected 87-year anthropogenic emissions. SOC sequestration would peak 2032-33,
      at that time reaching 4.3-8.9% of the projected annual SRES-A2 emission. About 30
      years later the sequestration rate would have reduced by half. Thus, SOC
      sequestration is not a C wedge that could contribute increasingly to mitigating
      CC. Rather, the mitigation potential is limited, contributing very little to
      solving the climate problem of the coming decades. However, we deliberately did
      not elaborate on the importance of maintaining or increasing SOC for sustaining
      soil health, agro-ecosystem functioning and productivity; an issue of global
      significance that deserves proper consideration irrespectively of any potential
      additional sequestration of SOC. 

PMID- 24929499
TI  - Effect of geochemical properties on degradation of trichloroethylene by
      stabilized zerovalent iron nanoparticle with Na-acrylic copolymer.
AB  - Stable nanoscale zero-valent iron (NZVI) particles have been developed to
      remediate chlorinated compounds. The degradation kinetics and efficiency of
      trichloroethylene (TCE) by a commercial stabilized NZVI with Na-acrylic copolymer
      (acNZVI) were investigated and compared with those by laboratory-synthesized NZVI
      and carboxymethyl cellulose (CMC)-stabilized NZVI particles. Results show that
      the degradation of TCE by acNZVI was faster than that by NZVI and CMC-NZVI.
      Increase in temperature enhanced the degradation rate and efficiency of TCE with
      acNZVI. The activation energy of TCE degradation by acNZVI was estimated to be 23
      kJ/mol. The degradation rate constants of TCE decreased from 0.064 to 0.026 min(
      1) with decrease in initial pH from 9.03 to 4.23. Common groundwater anions
      including NO3(-), Cl(-), HCO3(-), and SO4(2-) inhibited slightly the degradation
      efficiencies of TCE by acNZVI. The Na-acrylic copolymer-stabilized NZVI, which
      exhibited high degradation kinetics and efficiency, could be a good remediation
      agent for chlorinated organic compounds. 

PMID- 24929500
TI  - Assessment of the role of agricultural wastes in aggregate formation and their
      stability.
AB  - The purpose of this study was to evaluate the effects of three agricultural
      processing wastes (APWs) on aggregate formation and aggregate stability in a
      sandy loam textured soil (Typic Xerofluvent) in Antalya, Turkey. The effects of
      APW applications on aggregate formation and aggregate stability were observed for
      different aggregate size groups (>4; 4-2; 2-1; 1-0.5; 0.5-0.25; 0.25-0.050 and
      <0.050 mm). Sugar Beet Pulp (SBP), Apple Pomace (AP) and Cotton Gin Waste (CGW)
      were applied to soil as fresh material (dry weight basis 0, 10, 20 and 40 t ha(
      1)), and a greenhouse pot experiment was conducted using a completely randomized
      design with five replicates of each treatment. The study consisted of two
      periods. The first period (P1) consisted of a six-month incubation period (1st
      sample period). The second period (P2) is a six-month period and includes an
      eight-week green bean (Phaseolus vulgaris L.) growing process (2nd sample
      period). At the end of the first six months and fourteen months in total,
      aggregate formation and aggregate stability were determined and their correlation
      to different C sources was explained. At the end of the experiment, formation of
      aggregates was increased with increase in the application level of organic wastes
      in particular intermediate aggregates. Increase in the incubation time
      significantly enhanced the formation of particular macroaggregates. Soil
      aggregate stability of all aggregate sizes generally increased with the
      increasing in the level of implementation. In addition, incubation time effects
      on aggregate stability for macroaggregates were not significant, but significant
      for macro and microaggregates. 

PMID- 24929501
TI  - Investigations of metal leaching from mobile phone parts using TCLP and WET
      methods.
AB  - Metal leaching from landfills containing end-of-life or otherwise discarded
      mobile phones poses a threat to the environment as well as public health. In the
      present study, the metal toxicity of printed wire boards (PWBs), plastics, liquid
      crystal displays (LCDs) and batteries of mobile phones was assessed using the
      Toxicity Characteristics Leaching Procedures (TCLP) and the Waste Extraction Test
      (WET). The PWBs failed TCLP for Pb and Se, and WET for Pb and Zn. In WET, the two
      PWB samples for Pb and Zn and the battery samples for Co and Cu failed the test.
      Furthermore, the PWBS for Ni and the battery samples for Ni and Co failed the WET
      in their TCLP leachates. Both, Ni and Co are the regulatory metals in only WET
      and not covered under TCLP. These observations indicate that the TCLP seems to be
      a more aggressive test than the WET for the metal leaching from the mobile phone
      parts. The compositional variations, nature of leaching solution (acetate in TCLP
      and citrate in WET) and the redox conditions in the leaching solution of the PWBs
      resulted in different order of metals with respect to their amounts of leaching
      from PWBs in TCLP (Fe > Pb > Zn > Ni > Co > Cu) and WET (Zn > Fe > Ni > Pb > Cu).
      The metal leaching also varied with the make, manufacturing year and part of the
      mobile phone tested. PWBs, plastics and batteries should be treated as hazardous
      waste. Metal leaching, particularly of Se and Pb, from mobile phones can be
      harmful to the environment and human health. Therefore, a scientifically sound
      and environmentally safe handling and disposal management system needs to be
      evolved for the mobile phone disposal. 

PMID- 24929502
TI  - Effect of cation type, alkyl chain length, adsorbate size on adsorption kinetics
      and isotherms of bromide ionic liquids from aqueous solutions onto microporous
      fabric and granulated activated carbons.
AB  - The adsorption from aqueous solution of imidazolium, pyrrolidinium and pyridinium
      based bromide ionic liquids (ILs) having different alkyl chain lengths was
      investigated on two types of microporous activated carbons: a fabric and a
      granulated one, well characterized in terms of surface chemistry by "Boehm"
      titrations and pH of point of zero charge measurements and of porosity by N2
      adsorption at 77 K and CO2 adsorption at 273 K. The influence of cation type,
      alkyl chain length and adsorbate size on the adsorption properties was analyzed
      by studying kinetics and isotherms of eight different ILs using conductivity
      measurements. Equilibrium studies were carried out at different temperatures in
      the range [25-55  degrees C]. The incorporation of ILs on the AC porosity was
      studied by N2 adsorption-desorption measurements at 77 K. The experimental
      adsorption isotherms data showed a good correlation with the Langmuir model.
      Thermodynamic studies indicated that the adsorption of ILs onto activated carbons
      was an exothermic process, and that the removal efficiency increased with
      increase in alkyl chain length, due to the increase in hydrophobicity of long
      chain ILs cations determined with the evolution of the calculated octanol-water
      constant (Kow). The negative values of free energies indicated that adsorption of
      ILs with long chain lengths having hydrophobic cations was more spontaneous at
      the investigated temperatures. 

PMID- 24929503
TI  - Studying functional properties of hydrogel and silicone-hydrogel contact lenses
      with PALS, MIR and Raman spectroscopy.
AB  - Determination of free volume holes of the hydrogel and silicone-hydrogel polymer
      contact lenses were investigated. Two types of polymer contact lenses were used
      as materials: the first is a hydrogel contact lenses Proclear family (Omafilcon
      A), while the second is a silicone-hydrogel contact lens of the family Biofinity
      (Comfilcon A). Positron annihilation lifetime spectroscopy PALS was used to
      characterize geometrical sizes and fraction of the free volume holes in the
      investigated samples. There is a clear difference in the free volume sizes and
      their fractions between silicone-hydrogel and polymer hydrogel contact lenses
      which in turn are connected with oxygen permeability in these lenses. Apart from
      that, spectroscopic (middle infrared) MIR and Raman examinations were carried out
      in order to demonstrate the differences of the water content in the test contact
      lenses. 

PMID- 24929504
TI  - Using an Ecosystem Approach to complement protection schemes based on organism
      level endpoints.
AB  - Radiation protection goals for ecological resources are focussed on ecological
      structures and functions at population-, community-, and ecosystem-levels. The
      current approach to radiation safety for non-human biota relies on organism-level
      endpoints, and as such is not aligned with the stated overarching protection
      goals of international agencies. Exposure to stressors can trigger non-linear
      changes in ecosystem structure and function that cannot be predicted from effects
      on individual organisms. From the ecological sciences, we know that important
      interactive dynamics related to such emergent properties determine the flows of
      goods and services in ecological systems that human societies rely upon. A
      previous Task Group of the IUR (International Union of Radioecology) has
      presented the rationale for adding an Ecosystem Approach to the suite of tools
      available to manage radiation safety. In this paper, we summarize the arguments
      for an Ecosystem Approach and identify next steps and challenges ahead pertaining
      to developing and implementing a practical Ecosystem Approach to complement
      organism-level endpoints currently used in radiation safety. 

PMID- 24929505
TI  - Study of indoor radon distribution using measurements and CFD modeling.
AB  - Measurement and/or prediction of indoor radon ((222)Rn) concentration are
      important due to the impact of radon on indoor air quality and consequent
      inhalation hazard. In recent times, computational fluid dynamics (CFD) based
      modeling has become the cost effective replacement of experimental methods for
      the prediction and visualization of indoor pollutant distribution. The aim of
      this study is to implement CFD based modeling for studying indoor radon gas
      distribution. This study focuses on comparison of experimentally measured and CFD
      modeling predicted spatial distribution of radon concentration for a model test
      room. The key inputs for simulation viz. radon exhalation rate and ventilation
      rate were measured as a part of this study. Validation experiments were performed
      by measuring radon concentration at different locations of test room using active
      (continuous radon monitor) and passive (pin-hole dosimeters) techniques. Modeling
      predictions have been found to be reasonably matching with the measurement
      results. The validated model can be used to understand and study factors
      affecting indoor radon distribution for more realistic indoor environment. 

PMID- 24929506
TI  - Uncertainty related to input parameters of (137)Cs soil redistribution model for
      undisturbed fields.
AB  - This study presents an alternative method to empirically establish the effective
      diffusion coefficient and the convective velocity of (137)Cs in undisturbed
      soils. This approach offers the possibility to improve the parameterisation and
      the accuracy of the (137)Cs Diffusion and Migration Model (DMM) used to assess
      soil erosion magnitudes. The impact of the different input parameters of this
      radiometric model on the derived-soil redistribution rates has been determined
      for a Romanian pastureland located in the northwest extremity of the
      Transylvanian Plain. By fitting the convection-diffusion equation to the
      available experimental data, the diffusion coefficient and convection velocity of
      (137)Cs in soil could be determined; 72% of the (137)Cs soil content could be
      attributed to the (137)Cs fallout originating from Chernobyl. The medium-term net
      erosion rate obtained with the calculated input parameters reached -6.6 t ha(-1)
      yr(-1). The model highlights great sensitivity to parameter estimations and the
      calculated erosion rates for undisturbed landscapes can be highly impacted if the
      input parameters are not accurately determined from the experimental data set.
      Upper and lower bounds should be established based on the determined uncertainty
      budget for the reliable estimates of the derived redistribution rates. 

PMID- 24929507
TI  - Comparison of modern pollen distribution between the northern and southern parts
      of the South China Sea.
AB  - The authors conducted a palynological analysis based on different number of air
      pollen samples for the northern and southern parts of the South China Sea,
      respectively, in order to give a reference to reconstruct the paleoclimate of the
      area. (1) Fifteen air pollen samples were collected from the northern part of the
      South China Sea from August to September 2011, and 13 air pollen samples were
      collected from the southern part of the South China Sea in December 2011. The
      pollen types were more abundant in the north than in the south. The total pollen
      number and concentration in the north was 10 times more than that in the south,
      which may be because of the sampling season. Airborne pollen types and
      concentrations have a close relationship with wind direction and distance from
      the sampling point to the continent. (2) Seventy-four samples were collected from
      surface sediments in the northern part of the South China Sea in the autumn.
      Thirty-three samples were collected from surface sediments in the southern part
      of the South China Sea in the winter. Pollen concentrations in the north were
      nearly 10 times higher than that in the south. This is because trilete spores are
      transported by rivers from Hainan Island to the sea and also by the summer
      monsoon-forced marine current. (3) Ten air pollen samples and 10 surface
      sediments samples were selected for comparison. The pollen and spores in the air
      were mainly herbaceous and woody pollen, excluding fern spores, having seasonal
      pollen characteristics. Pollen in the surface sediments were mainly trilete,
      Pinus, and herbaceous, and may also show a combination of annual pollen
      characteristics. 

PMID- 24929508
TI  - [Progress in early pancreas development and reprogramming of terminally
      differentiated cells into beta cells].
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the immune
      system attacks insulin-secreting beta cells, thus leading to an absolute
      deficiency of insulin. Patients must rely on exogenous insulin, which cannot
      effectively prevent diabetes complications. Generation of insulin-secreting cells
      by reprogramming of pluripotent stem cells or somatic cells is a potential
      approach for the treatment of T1DM. These cells can be used for cell therapy and
      drug screening, and may eventually provide a cure for the disease. Significant
      progress has been made in generating insulin-secreting cells through the
      expression of beta cell specific transcription factors in stem cells or somatic
      cells. In this review, we summarize recent research progress in early pancreas
      development, beta cell specific transcription factors and reprogramming of
      terminally differentiated cells into beta cells. 

PMID- 24929509
TI  - [The molecular mechanism of necroptosis].
AB  - Programmed necrosis called necroptosis, is different from traditional necrosis
      and apoptosis, it has attracted considerable attention over the last few years.
      Necroptosis can be initiated through many factors such as tumor necrosis factor
      receptor (TNFR) or pattern recognition receptor (PRR), and receptor-interacting
      protein (RIP) 1 and 3 are two key proteins during the process. A lot of molecules
      have been characterized as modulators and effectors of necroptosis, including
      poly(ADP-ribose) polymerase (PARP-1), reactive oxygen species (ROS), Ca(2+),
      which can destruct mitochondria or other organelles and induce cell dead through
      caspase-independent pathway. Then, damage-associated molecular pattern (DAMP)
      molecules were released from necroptosis cells, recognized and internalized by
      phagocytes. Here, we briefly discuss the initiation and execution of necroptosis
      and the clearance of death cells. 

PMID- 24929510
TI  - [Role of genes and their cis-regulatory elements during animal morphological
      evolution].
AB  - Cis-regulatory hypothesis is one of the most important theories in evolutionary
      developmental biology (evo-devo), which claims that evolution of cis-regulatory
      elements (CREs) plays a key role during evolution of morphology. However, an
      increasing number of experimental results show that cis-regulatory hypothesis
      alone is not far enough to explain the complexity of evo-devo processes. Other
      modifications, including mutations of protein coding, gene and genome
      duplications, and flexibility of homeodomains and CREs, also cause the
      morphological changes in animals. In this review, we retrospect the recent
      results of evolution of CREs and genes associated with CREs and discuss new
      methods and trends for research in evo-devo.

PMID- 24929511
TI  - [Structure and biological functions of plant FKBP family].
AB  - FK506-binding proteins (FKBPs) are well known as both the receptor for the
      immunosuppressant drug FK506 and the prolyl isomerase (PPIase) enzyme. FKBPs are
      widely and constitutively expressed, and highly conserved during evolution. In
      higher plants, FKBPs usually form a relative large and diverse family compared
      with that in other eukaryotes, and serve as important molecular chaperones that
      interact with specific protein partners to regulate a diversity of cellular
      processes which mainly influence the plant development and stress responding.
      More recently, studies discovered a series of new interacting partners of FKBPs,
      which implicate FKBPs in gene expression regulation and photosynthetic
      adaptation. This review mainly focuses on the structural characteristics,
      classification, and the latest discoveries in the physiological functions of
      FKBPs in higher plants. 

PMID- 24929512
TI  - [Molecular mechanisms of SNARE proteins in regulating autophagy].
AB  - Autophagy is a self-protective mechanism that degrades inner and outer invaded
      substances to sustain self-maintenance. SNARE (Soluble N-ethylmaleimide-sensitive
      factor attachment protein receptors) hypothesis suggests important roles of SNARE
      proteins in the cellular activities of substance transport and specific membrane
      fusion, unveiling the molecular mechanisms of normal and physiological activities
      within a cell. Since autophagy involves membrane fusions from the birth of
      autophagosomes to the formation of autolysosomes, we review recent research
      progress on the roles of SNARE proteins in regulating autophagy. 

PMID- 24929513
TI  - [Screening of azoospermia factor microdeletions on Y chromosome in infertile men
      by QF-PCR].
AB  - To assess the application of quantitative fluorescent polymerase chain reaction
      (QF-PCR) on rapid screening of azoospermia factor (AZF) microdeletions, 1218
      infertile men with non-obstructive azoospermia or oligospermia were detected for
      9 sequence tagged sites (STSs) in AZF region by multiplex QF-PCR combined with
      capillary electrophoresis. AMEL (amelogenin) as well as SRY (sex-determining
      region of Y chromosome) located on short arm of sex chromosome was selected as
      internal control. Karyotyping was performed on Giemsa-banded metaphase
      chromosomes of peripheral blood lymphocytes. Of the 1218 patients, 105 (8.62%)
      were identified as AZF microdeletions. Deletion of AZFc (67.62%) was the most
      frequent, followed by deletion of AZFb,c (20.95%), AZFb (7.62%) and AZFa (3.81%).
      Five patients presented with deletions of both AZFa,b,c and AMEL-Y, indicating
      sex reversal which was confirmed to be 46,XX by karyotyping. Among the 105
      patients with AZF microdeletions, 16 were karyotyped as chromosomal anomalies,
      most commonly 46,XY,Yqh- (75%, 12/16). In addition, of the total 1218 patients
      examined, 86 patients showed abnormal AMEL-X/AMEL- Y ratio, suggesting a
      possibility of sex chromosome anomalies, and 68 of them were verified as sex
      chromosome aneuploid by karyotyping. Multiplex QF-PCR is capable to detect all
      markers in one reaction and is also suggestive for sex chromosome anomalies. It
      could serve as an effective technique for screening Y-microdeletions, and thus
      have general application in diagnosis and treatment of male infertility. 

PMID- 24929514
TI  - [Identification of chromosomal aberration in esophageal cancer cells by mixed BAC
      DNA probes of chromosome arms and regions].
AB  - Chromosomal aberration is an important genetic feature of malignant tumor cells.
      This study aimed to clarify whether BAC DNA could be used to identify chromosome
      region and arm alterations. For each chromosome region, five to ten 1 Mb BAC DNA
      clones were selected to construct mixed BAC DNA clones for the particular region.
      All of the mixed clones from regions which could cover the whole chromosome arm
      were then mixed to construct mixed BAC DNA clones for the arms. Mixed BAC DNA
      probes of arms and regions were labeled by degenerate oligonucleotide primed PCR
      (DOP-PCR) and Nick translation techniques, respectively. The specificities of
      these probes were validated by fluorescence in situ hybridization (FISH) on the
      metaphase chromosomes of normal human peripheral blood lymphocytes. FISH with arm
      specific mixed BAC DNA probes showed that chromosomal rearrangements and involved
      chromosome arms were confirmed in several esophageal cancer cells. By using
      region-specific mixed probes, the breakpoint on 1q from the derivative chromosome
      t(1q;7q) was identified in 1q32-q41 in esophageal KYSE140 cells. In conclusion,
      we established an effective labeling method for 1 Mb BAC DNA mixed clone probes,
      and chromosome arm and region rearrangements could be identified in several
      esophageal cancer cells by using these probes. Our study provides a more precise
      method for identification of chromosomal aberration by M-FISH, and the
      established method may also be applied to the karyotype analysis of hematological
      malignancies and prenatal diagnosis. 

PMID- 24929515
TI  - [Blueberry anthocyanins induce G2/M cell cycle arrest and apoptosis of oral
      cancer KB cells through down-regulation methylation of p53].
AB  - Blueberries are an excellent source of dietary polyphenols such as anthocyanins
      and phenolic acids. In this study, we investigated the ability of anthocyanins
      from the wild blueberries of Inner Mongolia to suppress the growth of the oral
      cancer cell line KB. The blueberry anthocyanins were extracted with methanol
      containing 0.1% (v/v) hydrochloric acid. Fourteen unique anthocyanins were
      identified using high-performance liquid chromatography-mass spectrometry (HPLC
      MS). The anticancer bioactivity of the extracts on KB cells was analyzed using
      methylthiazolyl-tetrazolium (MTT), flow cytometry (FCM) and immunocytochemistry.
      It was shown that the blueberry anthocyanins suppressed the proliferation of KB
      cells in a dose-dependent manner, as well as induced G2/M cell cycle arrest and
      apoptosis of oral cancer KB cells. Immunocytochemistry analysis showed that the
      expression of caspase-9 and cytochrome c were obviously increased after the
      anthocyanins treatment. Western blot analysis also indicated that the expression
      of p53 was increased. Methylation-specific PCR (MSP) showed that the amount of
      unmethylated p53 increased, indicating that the anthocyanins can down-regulate
      the methylation of p53. 

PMID- 24929516
TI  - [Differentially expressed genes identified in the main olfactory epithelium of
      mice with deficiency of adenylate cyclase 3 by using suppression subtractive
      hybridization approach].
AB  - Adenylate cyclase 3 (AC3) is one of the major players in the olfactory signaling
      within the main olfactory epithelium (MOE) of mice. However, we are not
      ascertained whether deficiency of AC3 will lead to the differential expression of
      related genes in the MOE. Forward and reverse subtractive libraries were
      constructed by suppression subtractive hybridization (SSH) approach, with MOEs
      from AC3(-/-) and AC3(+/+) mice. These two libraries were primarily screened by
      Dot blot, differential expressed clones were sequenced and analyzed by
      bioinformatics, and differential expressed genes were verified by qRT-PCR. A
      total of 386 differentially expressed clones were picked out after Dot blot. The
      DNA sequences of 80 clones randomly selected were determined, and 62 clones were
      identified by blasting in GenBank. We found that 24 up-regulated clones were
      corresponded to genes of kcnk3, mapk7, megf11, and 38 down-regulated clones were
      corresponded to tmem88b, c-mip, skp1a, mlycd, etc. Their functions were annotated
      with Gene Ontology (GO) and found to be mainly focused on molecular binding, cell
      cycle, processes of biology and cells. Five genes (kcnk3, c-mip, mlycd, tmem88b
      and trappc5) were verified by qRT-PCR with individuals of AC3(+/+) and AC3(-/-)
      mice. The data indicate that kcnk3 gene is up-regulated significantly, increasing
      1.27 folds compared to control mice, whereas c-mip, mlycd, tmem88b and trappc5
      are down-regulated significantly, decreasing 20%, 7%, 32% and 29% compared to the
      AC3(+/+)mice. The functions of these genes are closely related with K(+)
      channels, cell differentiation, metabolism of fats, membrane transportation, and
      so on. It is tempting to speculate that these genes might work together with AC3
      to orchestrate the olfactory transduction signaling in the MOE. 

PMID- 24929517
TI  - [Cloning and functional validation of promoter of mo-molybdopterin cofactor
      sulfurase gene in maize].
AB  - To overcome the problems caused by the over-expression of exogenous genes under
      the control of constitutive promoters, the promoter (ABA3s) sequence of maize
      (Zea mays) mo-molybdopterin cofactor sulfurase gene (ABA3) was cloned
      homologously, analyzed for its abiotic stress-responsive elements by the
      PlantCARE software, and detected for differential expression of the ABA3 gene
      under the abiotic stresses by real-time quantitative PCR. Then, this promoter was
      used to construct expression vector to start GUS (beta-glucuronidase) gene, and
      transform maize calli by biolistics. After identification by histochemical
      staining, the ratio of the GUS activity relative to the luciferase activity
      (internal control) (GUS/LUC) was measured under the stresses of hypertonic, high
      salt, low temperature, and the induction of ABA, and used to evaluate the
      activity of the ABA3s promoter in response to abiotic stresses. The results
      showed that the ABA3 gene was differentially expressed under the stress of
      simulative drought, low temperature, high temperature, high salt, and the
      induction of ABA and ethylene, indicating that the promoter (ABA3s) of this gene
      is induced by abtiotic stress. The sequence analysis showed that the ABA3s
      promoter is 777 bp long, and contains abiotic stress-responsive elements ARE,
      HSE, MBS, TGA and circadian. The transformed calli by the expression vector of
      the GUS gene under the control of the ABA3s promoter showed positive in GUS
      detection in response to the abiotic stresses of drought, low temperature, high
      temperature, high salt, and the induction of ABA and ethylene. The GUS/LUC ratio
      was six folds higher than the blank control under the hypertonic stress of 8%
      mannitol. It is concluded that the promoter ABA3s is inducible in response to
      abiotic stresses, and might be applied to transgenic research of maize for
      abiotic tolerance after further functional evaluation.

PMID- 24929519
TI  - [Structure and function of class 1 integron in clinical isolates of Klebsiella
      pneumoniae].
AB  - To investigate molecular mechanism of multi-resistance of Klebsiella pneumoniae
      and its spreading, 179 strains isolated from different clinical samples in the
      period of 2002-2007 with serious resistance to 14 anti-bacterial agents were
      examined. Among them, 118 (65.9%) were resistant to at least two anti-bacterial
      agents; 36.3% (65/179) were found to contain class 1 integrons. There was a
      significant difference for resistance rate between the integron positive and the
      negative groups, especially for antimicrobial agents of aminoglycosides,
      quinolones and sulfonamides (P<0.01). Gene cassette structures of the class 1
      integrons in these bacteria were analyzed and their resistance genes were further
      cloned and tested for antibiotic resistance activities. Fifteen gene cassettes
      were identified with dfrA17-aadA5 being the most popular form. Three recombinant
      plasmids pET28a-dhfr17, pET28a-dhfr17-orfF and pET28a-dhfr17-orfF-aadA2 were
      cloned from a gene cassette of dhfr17-orfF-aadA2. When introduced into a
      recipient E. coli strain BL21, all of them rendered resistance to co-trimoxazole,
      with minimum inhibitory concentration (MIC) value up to 256 ug/uL. The E. coli
      BL21 carrying pET28a- dhfr17 or pET28a-dhfr17-orfF had the same MIC value of 8
      ug/uL to streptomycin as the recipient strain without plasmid. However, the E.
      coli carrying pET28a-dhfr17-orfF-aadA2 was resistant to streptomycin with MIC
      level up to 256 ug/uL. In conclusion, class 1 integrons were regularly identified
      in Klebsiella pneumoniae. They mainly carry resistance genes against
      antimicrobial agents of aminoglycosides and sulfonamide. Transferable plasmid
      carrying integrons with resistance genes may play an important role in resistance
      spreading among bacterial species. 

PMID- 24929518
TI  - [Cloning of tae-MIR156 precursor gene and sequence polymorphisms of tae-miR156
      targeted TaSPL17].
AB  - Squamosa-promoter binding protein (SBP)-box genes, encoding plant-specific
      transcription factors, play an important role in plant development. Some members
      of the SBP-box gene family are regulated by miR156. In this study, we cloned the
      tae-MIR156 precursor gene, which could form a stem loop after its transcription.
      Sequence analysis showed that TaSPL3 and TaSPL17 had putative targets of tae
      miR156 among the ten wheat SBP-box genes. The diploid donor species of hexaploid
      common wheat (Triticum aestivum, genome AABBDD), i.e., Triticum urartu (AA) UR209
      and Aegilops speltoides Y2001 (SS, closely related to BB) possessed more than one
      copy of SPL17 (SPL17-A1, SPL17-A2 and SPL17-A3 from Triticum urartu; SPL17-B1,
      SPL17-B2 and SPL17-B3 from Aegilops speltoides), while Aegilops tauschii (DD)
      Ae38 only possessed one (SPL17-D). The identities between nucleotide sequences of
      SPL17-A2 and SPL17-B2, SPL17-A3 and SPL17-B3 or SPL17-D were higher than 99%.
      They were highly similar with the sequence of TaSPL17 in common wheat cultivars
      Chinese Spring, Hengguan 35 and Shuangfengshou. These genes might originate from
      a common ancestor and were highly conserved in the process of evolution. The
      target site of tae-miR156 in TaSPL17 was also highly conserved in two subgroups
      consisted of accessions with diverse spike number per plant and genetic
      background. 

PMID- 24929520
TI  - [Elucidation of key genes in sex determination in genetics teaching].
AB  - Sex is an important and complex feature of organisms, which is controlled by the
      genetic and environmental factors. The genetic factors, i.e., genes, are vital in
      sex determination. However, not all the related genes play the same roles, and
      some key genes play a vital role in the sex determination and differentiation.
      With the development of the modern genetics, a great progress on the key genes
      has been made in sex determination. In this review, we summarize the mechanism of
      sex determination and the strategy of how to study the key genes in sex
      determination. It will help us to understand the mechanism of sex determination
      better in the teaching of genetics. 

PMID- 24929521
TI  - [Automatic analysis pipeline of next-generation sequencing data].
AB  - The development of next-generation sequencing has generated high demand for data
      processing and analysis. Although there are a lot of software for analyzing next
      generation sequencing data, most of them are designed for one specific function
      (e.g., alignment, variant calling or annotation). Therefore, it is necessary to
      combine them together for data analysis and to generate interpretable results for
      biologists. This study designed a pipeline to process Illumina sequencing data
      based on Perl programming language and SGE system. The pipeline takes original
      sequence data (fastq format) as input, calls the standard data processing
      software (e.g., BWA, Samtools, GATK, and Annovar), and finally outputs a list of
      annotated variants that researchers can further analyze. The pipeline simplifies
      the manual operation and improves the efficiency by automatization and parallel
      computation. Users can easily run the pipeline by editing the configuration file
      or clicking the graphical interface. Our work will facilitate the research
      projects using the sequencing technology. 

PMID- 24929522
TI  - The critical role of didodecyldimethylammonium bromide on physico-chemical,
      technological and biological properties of NLC.
AB  - Exploiting the experimental factorial design and the potentiality of Turbiscan AG
      Station, we developed and characterized unmodified and DDAB-coated NLC prepared
      by a low energy organic solvent free phase inversion temperature technique. A 22
      full factorial experimental design was developed in order to study the effects of
      two independent variables (DDAB and ferulic acid) and their interaction on mean
      particle size and zeta potential values. The factorial planning was validated by
      ANOVA analysis; the correspondence between the predicted values of size and zeta
      and those measured experimentally confirmed the validity of the design and the
      equation applied for its resolution. The DDAB-coated NLC were significantly
      affected in their physico-chemical properties by the presence of DDAB, as showed
      by the results of the experimental design. The coated NLC showed higher physical
      stability with no particles aggregation compared to the unmodified NLC, as
      demonstrated by Turbiscan((r)) AGS measurements. X-ray diffraction, Raman
      spectroscopy and Cryo-TEM images allowed us to assert that DDAB plays a critical
      role in increasing the lipids structural order with a consequent enhancement of
      the NLC physical stability. Furthermore, the results of the in vitro biological
      studies allow the revisiting of the role of DDAB to the benefit of glioblastoma
      treatment, due to its efficacy in increasing the NLC uptake and reducing the
      viability of human glioblastoma cancer cells (U87MG). 

PMID- 24929523
TI  - Analytical characterization and purification of a commercial extract of enzymes:
      a case study.
AB  - This paper presents a rational strategy to identify and quantify the components
      of a commercial extract of the lipase B of Candida antarctica that can be
      extended to the analytical investigation of other crude extracts of enzymes.
      These information provided the fundamental knowledge for the development of a
      methodology to obtain highly pure and catalytically active CALB enzyme. The
      commercial extract Lipozyme((r)) was subjected to a series of analytical
      techniques that allowed determining the presence of a non-soluble fraction;
      nucleic acids; benzoate and sorbate species and a mixture of three proteins.
      Particularly, it is worth noticing that the Bradford assay using CALB as standard
      instead of BSA proved to be a more reliable and accurate methodology to quantify
      the protein content of the assayed enzymatic samples. Size exclusion
      chromatography coupled with anionic exchange chromatography using a non
      conventional, easy to remove buffer system such as ammonia-ammonium acetate
      afforded a sample that retains 47% of the proteins (being CALB the only enzymatic
      component of the purified sample) with a hydrolytic activity higher than the
      crude extract. 

PMID- 24929524
TI  - Phenylboronic acid polymer brush-enabled oriented and high density antibody
      immobilization for sensitive microarray immunoassay.
AB  - There still has a big challenge for low-abundance protein detection with antibody
      microarrays. In this work, phenylboronic acid (PBA) polymer brush-enabled
      oriented, high density, and covalent antibody immobilization was realized for
      sensitive antibody microarrays. PBA-enabled oriented antibody attachment via
      carbohydrate at Fc portion keeps antigen-binding sites fully expose to their
      corresponding antigens, resulting in higher antibody-antigen (Ab-Ag) binding
      efficiency. Sandwich immunoassay with rabbit IgG as model analyte was performed
      on poly(glycidyl methacrylate)-amino-phenylboronic acid-coated glass slide (PGMA
      APBA-slide). One order improvement of LOD was achieved as compared with that on
      poly(glycidyl methacrylate) glass slide (PGMA-slide). The improvement is mainly
      attributed to PBA-assisted high density and oriented antibody immobilization.
      This work provides a versatile and effective strategy to develop high sensitive
      antibody microarrays for low-abundance protein analysis in various proteomic
      applications. 

PMID- 24929525
TI  - The expression of the multiple splice variants of AQP8 in porcine testes at
      different developmental stages.
AB  - Aquaporin 8 (AQP8) may be involved in cytoplasmic condensation and fluid
      formation in the vas deferens during the process of spermiogenesis. In the
      present study, using reverse transcription polymerase chain reaction (RT-PCR)
      combined with DNA sequencing technology, the splice isoforms of AQP8 post
      transcriptionally formed by alternative splicing in porcine testis at various
      developmental stages were analysed, and the differences in the amino acid
      sequences encoded by the splice isoforms were compared. The results showed that a
      total of three splice isoforms of AQP8 mRNA, including full-length mRNA, were
      produced via alternative splicing in porcine testes at the four developmental
      stages. Because the number of bases removed during splicing was not an integer
      multiple of 3, the amino acid sequence and protein structure of AQP8 were
      significantly altered after alternative splicing.

PMID- 24929526
TI  - Thermoluminescence dosimetry properties and kinetic parameters of lithium
      potassium borate glass co-doped with titanium and magnesium oxides.
AB  - Lithium potassium borate (LKB) glasses co-doped with TiO2 and MgO were prepared
      using the melt quenching technique. The glasses were cut into transparent chips
      and exposed to gamma rays of (60)Co to study their thermoluminescence (TL)
      properties. The TL glow curve of the Ti-doped material featured a single
      prominent peak at 230  degrees C. Additional incorporation of MgO as a co
      activator enhanced the TL intensity threefold. LKB:Ti,Mg is a low-Z material
      (Z(eff)=8.89) with slow signal fading. Its radiation sensitivity is 12 times
      lower that the sensitivity of TLD-100. The dose response is linear at doses up to
      10(3) Gy. The trap parameters, such as the kinetics order, activation energy, and
      frequency factor, which are related to the glow peak, were determined using
      TolAnal software.

PMID- 24929528
TI  - DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets.
AB  - To identify physiological targets of drugs and bioactive small molecules, we
      developed an approach, named DrugTargetSeqR, which combines high-throughput
      sequencing, computational mutation discovery and clustered regularly interspaced
      short palindromic repeats (CRISPR)-Cas9-based genome editing. We applied this
      approach to ispinesib and YM155, drugs that have undergone clinical trials as
      anticancer agents, and uncovered mechanisms of action and identified genetic and
      epigenetic mechanisms likely to cause drug resistance in human cancer cells. 

PMID- 24929527
TI  - Small-molecule modulation of Ras signaling.
AB  - Despite intense efforts in pharmaceutical industry and academia, a therapeutic
      grip on oncogenic Ras proteins has remained elusive. Mutated Ras is associated
      with ~20-30% of all human cancers often not responsive to established therapies.
      In particular, K-Ras, the most frequently mutated Ras isoform, is considered one
      of the most important but 'undruggable' targets in cancer research. Recently, new
      cavities on Ras for small-molecule ligands were identified, and selective direct
      targeting of mutated K-Ras(G12C) has become possible for what is to our knowledge
      the first time. In addition, impairment of Ras spatial organization, in
      particular via targeting the prenyl-binding Ras chaperone PDEdelta, has opened a
      fresh perspective in anticancer research. These recent advances fuel hopes for
      the development of new drugs targeting Ras.

PMID- 24929530
TI  - Interaction of fengycin with stratum corneum mimicking model membranes: a
      calorimetry study.
AB  - Based on its outstanding antifungal properties, it is reasonable to believe that
      fengycin might be efficient to topically treat localized dermatomycoses. Since
      most of the fungi species involved in the formation of those mycotic skin
      diseases colonize primarily the stratum corneum (SC), studying the interaction
      between fengycin and SC-mimicking lipid membranes is a primary step to determine
      the potential of fengycin to overcome the physical barrier of the skin. In this
      respect, multilamellar lipid vesicles (MLVs), with a lipid composition mimicking
      that of the SC, were prepared and characterized by differential scanning
      calorimetry (DSC). The critical micelle concentration (CMC) of fengycin was also
      assessed under skin conditions and found to be 1.2+/-0.1MUM. The molecular
      interactions of fengycin with SC-mimicking MLVs were investigated by both DSC and
      isothermal titration calorimetry (ITC). Results showed that the interactions were
      considerably affected by changes in lipid phase behaviour. At 40 degrees C and
      below, fengycin induced exothermic changes in the lipid structures suggesting
      that less-ordered lipid domains became more-ordered in presence of fengycin. At
      60 degrees C, clearly endothermic interaction enthalpies were observed, which
      could arise from the "melting" of remaining solid domains enriched in high
      melting lipids that without fengycin melt at higher temperatures. 

PMID- 24929529
TI  - DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian
      cells.
AB  - Identification and validation of drug-resistant mutations can provide important
      insights into the mechanism of action of a compound. Here we demonstrate the
      feasibility of such an approach in mammalian cells using next-generation
      sequencing of drug-resistant clones and CRISPR-Cas9-mediated gene editing on two
      drug-target pairs, 6-thioguanine-HPRT1 and triptolide-ERCC3. We showed that
      disrupting functional HPRT1 allele or introducing ERCC3 point mutations by gene
      editing can confer drug resistance in cells. 

PMID- 24929531
TI  - Intercellular pH-responsive histidine modified dextran-g-cholesterol micelle for
      anticancer drug delivery.
AB  - Herein, the micelles based on histidine modified dextran-g-cholesterol (HDC) were
      successfully prepared which exhibited excellent pH-responsive behavior in acidic
      aqueous solution (pH<6, within the range of malignant cellular endosome). Taking
      advantage of this pH-sensitivity in acidic conditions, doxorubicin (DOX), a model
      anticancer drug, was effectively loaded into the micelles via hydrophobic
      interactions. The DOX release from all DOX-loaded micelles was accelerated in
      acid conditions mimicking the endosomal/lysosomal compartments. The enhanced
      intracellular DOX release was also observed in MCF-7 cells. DOX-loaded pH
      sensitive micelles showed higher cellular proliferation inhibition toward MCF-7
      cells than that of pH-insensitive micelles. These features suggested that the
      micelles could efficiently load and deliver DOX into tumor cells, which can
      enhance the inhibition of cellular proliferation in vitro, providing a powerful
      mean for delivering and releasing cargoes at the tumor sites. 

PMID- 24929532
TI  - Transcranial magnetic motor evoked potentials in Great Danes with and without
      clinical signs of cervical spondylomyelopathy: association with neurological
      findings and magnetic resonance imaging.
AB  - Transcranial magnetic motor evoked potentials (TMMEPs) assess the functional
      integrity of the descending motor pathways, which are typically compromised in
      canine cervical spondylomyelopathy (CSM). The objective of this prospective study
      was to establish the reference ranges of TMMEP latency and amplitude in
      clinically normal (control) Great Danes (GDs), compare TMMEPs obtained in GDs
      with and without CSM, and determine whether there is any association between
      TMMEP data and severity of neurological signs or magnetic resonance imaging (MRI)
      findings. Twenty-nine client-owned GDs were enrolled (15 controls, 14 CSM
      affected). All dogs underwent TMMEPs under sedation, and latencies and amplitudes
      were recorded from the extensor carpi radialis (ECR) and cranial tibial (CT)
      muscles. MRI of the cervical vertebral column was performed to evaluate the
      presence and severity of spinal cord (SC) compression, and the presence of SC
      signal changes. ECR and CT latencies were significantly longer in CSM-affected
      than control GDs. No significant differences between groups were found for
      amplitudes or neuronal path lengths. For the CT TMMEPs, CSM-affected GDs with
      moderate and severe clinical signs had significantly longer latencies than those
      with mild clinical signs. Significantly longer CT latencies were found in dogs
      with moderate and severe SC compression compared with dogs with mild compression.
      CT TMMEPs could not be recorded in 7/9 CSM-affected GDs with SC signal changes.
      These results provide a reference range for TMMEPs of clinically normal GDs. The
      use of TMMEPs is a valid ancillary test to assess the integrity of motor pathways
      in GDs with CSM.

PMID- 24929533
TI  - Efficacy of passively transferred antibodies in cats with acute viral upper
      respiratory tract infection.
AB  - A commercial hyperimmune serum, containing antibodies against feline calicivirus
      (FCV), feline herpesvirus 1 (FHV-1), and feline panleukopenia virus, is available
      for treatment of cats with feline upper respiratory tract disease (FURTD), but
      its efficacy has not been rigorously evaluated in scientific studies. The aim of
      this randomised, placebo-controlled, double-blind clinical trial was to evaluate
      the efficacy of passive immunisation in cats with acute viral FURTD caused by FCV
      and/or FHV-1 infection. All cats received symptomatic treatment during the study
      period. Hyperimmune serum was administered to one group (n = 22) and an
      equivalent amount of saline was administered to the control group (n = 20) as
      placebo, for 3 consecutive days. In the treatment group, cats <=12 weeks old
      received 2 mL, cats >12 weeks old received 4 mL, subcutaneously once daily and
      topically into eyes, nostrils, and mouth every 8 h. Clinical signs, including a
      'FURTD score' and general health status, were recorded daily for 8 days and again
      on day 21. FCV shedding was determined by quantitative PCR on days 0 and 21.
      Clinical signs and health status in both groups improved significantly over time
      (P < 0.001). Cats receiving hyperimmune serum significantly improved in terms of
      'FURTD score' (P = 0.046) and general health status (P = 0.032) by day 3, while
      cats in the placebo group only improved significantly by day 7. There was no
      significant difference in the number of cats shedding FCV between the two groups.
      Thus, administration of hyperimmune serum led to a more rapid improvement of
      clinical signs in cats with acute viral FURTD, but by day 7, clinical signs had
      improved equally in both groups.

PMID- 24929534
TI  - Selection response to DNA testing for canine ceroid lipofuscinosis in Tibetan
      terriers.
AB  - A late onset form of canine ceroid lipofuscinosis (CCL) is prevalent in Tibetan
      terriers. The disease is inherited as a monogenic recessive trait caused by
      aberrant exon skipping in ATP13A2. The aim of the present study was to analyse
      the frequencies of this mutation in Tibetan terriers registered with the German
      club for Tibetan dog breeds (Internationaler Klub fur Tibetische Hunderassen,
      KTR) from 1987 to 2012 and to determine responses to selection following the
      introduction of DNA testing in 2010. The study included DNA extracted from blood
      samples from 1120/1240 (90.3%) Tibetan terriers registered with the KTR,
      including 405/420 (96.4%) registered breeding dogs. Mutant allele frequencies
      before the introduction of DNA testing were 0.20-0.28 in the registered and
      breeding dog populations, respectively, decreasing to 0.09 and 0.14,
      respectively, following the introduction of DNA testing.

PMID- 24929535
TI  - Charting a roadmap for heart failure biomarker studies.
AB  - Heart failure is a syndrome with a pathophysiological basis that can be traced to
      dysfunction in several interconnected molecular pathways. Identification of
      biomarkers of heart failure that allow measurement of the disease on a molecular
      level has resulted in enthusiasm for their use in prognostication and selection
      of appropriate therapies. However, despite considerable amounts of information
      available on numerous biomarkers, inconsistent research methodologies and lack of
      clinical correlations have made bench-to-bedside translations rare and left the
      literature with countless publications of varied quality. There is a need for a
      systematic and collaborative approach aimed at definitively studying the clinical
      benefits of novel biomarkers. In this review, on the basis of input from
      academia, industry, and governmental agencies, we propose a systematized approach
      based on adherence to specific quality measures for studies looking to augment
      current prediction model or use biomarkers to tailor therapeutics. We suggest
      that study quality, rather than results, should determine publication and propose
      a system for grading biomarker studies. We outline the need for collaboration
      between clinical investigators and statisticians to introduce more advanced
      statistical methodologies into the field of biomarkers that would allow for data
      from a large number of variables to be distilled into clinically actionable
      information. Lastly, we propose the creation of a heart failure biomarker
      consortium that would allow for a comprehensive list of biomarkers to be
      concomitantly analyzed in a pooled sample of randomized clinical trials and
      hypotheses to be generated for testing in biomarker-guided trials. Such a
      consortium could collaborate in sharing samples to identify biomarkers, undertake
      meta-analyses on completed trials, and spearhead clinical trials to test the
      clinical utility of new biomarkers. 

PMID- 24929536
TI  - Doxycycline administration improves fascial interface in hernia repair.
AB  - BACKGROUND: Despite improvements in ventral hernia repair techniques, their
      recurrence rates are unacceptably high. Increased levels of matrix
      metalloproteinases (MMPs) and reduced collagen-1 to -3 ratios are implicated in
      incisional hernia formation. We have recently shown doxycycline treatment for 4
      wk after hernia repair reduced MMP levels, significantly increased collagen-1 to 
      3 ratios, and increased tensile strength of repaired interface fascia. However,
      this increase was not statistically significant. In this study, we extended
      treatment duration to determine whether this would impact the tensile strength of
      the repaired interface fascia. MATERIALS AND METHODS: Thirty-two male Sprague
      Dawley rats underwent incision hernia creation and subsequent repair with
      polypropylene mesh. The animals received either saline (n = 16) or doxycycline (n
      = 16) beginning from 1 day before hernia repair until the end of survival time of
      6 wk (n = 16) or 12 wk (n = 16). Tissue samples were investigated for MMPs and
      collagen subtypes using Western blot procedures, and tensiometric analysis was
      performed. RESULTS: At both 6 and 12 wk after hernia repair, the tensiometric
      strength of doxycycline-treated mesh to fascia interface (MFI) tissue showed a
      statistically significant increase when compared with untreated control MFI. In
      both groups, collagen-1, -2, and -3 ratios were remarkably increased in
      doxycycline-treated MFI. At 6 wk, the doxycycline-treated MFI group showed a
      significant decrease in MMP-2, an increase in MMP-3, and no change in MMP-9. At
      12 wk, MMP-9 showed a remarkable reduction, whereas MMP-2 and -3 protein levels
      increased in the doxycycline-treated MFI group. CONCLUSIONS: Doxycycline
      administration results in significantly improved strength of repaired fascial
      interface tissue along with a remarkable increase in collagen-1, -2, and -3
      ratios.

PMID- 24929537
TI  - Meta-analysis demonstrates lack of association of the GSK3B -50C/T polymorphism
      with risk of bipolar disorder.
AB  - Published data on the association between GSK3B -50C/T (rs334558) and bipolar
      disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the
      relationship of this single-nucleotide polymorphism with the susceptibility, and
      with the age at onset of BD. A literature search was conducted though PubMed,
      EMBASE, Web of Science and China National Knowledge Infrastructure databases to
      identify relevant studies up to February 14, 2014. We identified a total of 6
      publications including 1,251 cases and 1,804 controls to investigate the effect
      of GSK3B -50C/T on BD risk, and found no significant association in any genetic
      models (C vs. T: OR = 1.03, 95 % CI: 0.92-1.15; CC vs. TT+TC: OR = 1.04, 95 % CI:
      0.84-1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97-1.39; and CC vs. TC vs. TT: OR
      = 1.08, 95 % CI: 0.96-1.22). Subgroup analysis by ethnicity did not change the
      results. The association between GSK3B -50C/T and age at onset of BD was explored
      by 6 identified studies with a total of 659 BD type I patients. Similarly, we did
      not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20,
      95 % CI: -0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: -0.10 to 0.32; CC vs.
      TT: SMD = 0.32, 95 % CI: -0.13 to 0.77). The power analysis and tests for
      publication bias ensured the reliability of our results. In summary, this meta
      analysis suggests that the functional polymorphism -50C/T within the GSK3B gene
      promoter is unlikely to relate with BD risk. However, more larger and well
      designed studies are still needed to yield a conclusive result on the topic.

PMID- 24929538
TI  - Molecular cloning and characterization of a lysozyme cDNA from the mole cricket
      Gryllotalpa orientalis (Orthoptera: Gryllotalpidae).
AB  - A full-length lysozyme cDNA from Gryllotalpa orientalis was cloned and sequenced.
      The deduced amino acid sequence of the lysozyme protein was 143 amino acids in
      length, with a calculated molecular mass of 15.84 kDa and an isoelectric point of
      4.74. Sequence motifs, together with alignment and phylogenetic results,
      confirmed that G. orientalis lysozyme belongs to the C (chicken)-type lysozyme
      family of proteins. The protein sequence of lysozyme from G. orientalis showed
      high identity to that of Drosophila melanogaster (51.7 %); however, in contrast
      to D. melanogaster lysozyme, G. orientalis lysozyme was immune inducible and
      expressed in a wide range of tissues. Expression of G. orientalis lysozyme mRNA
      was highest at 8 h post-infection and subsequently decreased with time after
      bacterial infection. We also expressed G. orientalis lysozyme protein in vitro
      using the pET expression system. Compared with the negative control, over
      expressed G. orientalis lysozyme showed antimicrobial activity against Gram
      negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis
      by radial diffusion assay, with minimal inhibitory concentration values of 30.3
      and 7.55 uM, respectively. These results indicate that G. orientalis lysozyme may
      have stronger antimicrobial activity than other lysozymes against a broad range
      of microorganisms.

PMID- 24929539
TI  - Resistin-induced stromal cell-derived factor-1 expression through Toll-like
      receptor 4 and activation of p38 MAPK/ NFkappaB signaling pathway in gastric
      cancer cells.
AB  - BACKGROUND: Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC
      chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric
      cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to
      distant organs. In addition, resistin is suggested to be an important link
      between obesity and the development of gastric cancer. Resistin has identified as
      an important player in inflammatory responses, and emerged as a mediator in
      inflammation-associated cancer. A limited number of studies have investigated the
      association of resistin and SDF-1 with gastric cancer. Herein, we investigated
      the molecular mechanisms by which resistin influences the expression of SDF-1 in
      gastric carcinoma cells. RESULTS: Human gastric cancer cell lines were exposed to
      doses of resistin; SDF-1 expression and secretion levels were then determined.
      Real-time polymerase chain reaction and western blotting analyses were performed
      to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a
      competitive antagonist inhibited resistin-induced SDF-1 expression.
      Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that
      activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical
      for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and
      transcription factor enzyme-linked immunosorbent assay revealed that resistin
      induced expression of SDF-1 mediated by NF-kappaB in gastric cancer cells.
      Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the
      SDF-1 promoter activity in the cancer gastric cells. Chromatin
      immunoprecipitation assay revealed that inhibition of p38 MARK activation also
      blocked the resistin-increased NF-kappaB-DNA-binding activity. CONCLUSIONS:
      Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-kappaB
      may explain a new role of resistin in the link of obesity and gastric cancer.

PMID- 24929540
TI  - The effect of coffee, tea, and caffeine consumption on serum uric acid and the
      risk of hyperuricemia in Korean Multi-Rural Communities Cohort.
AB  - Caffeine, a commonly consumed food constituent, is known to exert beneficial
      physiological effects in humans. There is a lack of comprehensive population data
      for the effects of caffeine intake on urate metabolism. Therefore, the aim of
      this study was to determine whether coffee, tea, and caffeine intake influences
      serum uric acid and the risk of hyperuricemia in the Korean Multi-Rural
      Communities Cohort. We enrolled 9,400 participants in this study. An assessment
      of various dietary intake amounts of substances such as coffee and tea was
      performed using a food frequency questionnaire. The content of caffeine was
      calculated from coffee (74 mg/cup) and tea (15 mg/cup) intake information from
      the past year. Multivariate logistic regression models, multiple linear
      regression models, and analysis of covariance were applied to identify any
      association of dietary intake with serum uric acid levels or the risk of
      hyperuricemia. No trends for coffee, tea, or caffeine intake were found according
      to each quintile with serum uric acid in males, although there were weak,
      marginally significant trends between the content of coffee and caffeine intake
      and serum uric acid level in females (p = 0.07 for both). Tea intake in males and
      caffeine intake in females were significantly different between non-hyperuricemia
      and hyperuricemia (p = 0.04 and p = 0.04, respectively). In addition, a
      significant association of serum uric acid level with tea intake in males (beta =
      0.0006, p = 0.02) and with tea intake and caffeine intake in females (beta =
      0.0003, p = 0.04 and beta = 0.0006, p = 0.02, respectively) was observed. There
      was no effect of coffee, tea, or caffeine intake on the risk of hyperuricemia in
      either males or females. This study suggests that caffeine consumption might have
      an effect on serum uric acid in females. However, coffee, tea, and caffeine
      intake amounts were not associated with the risk of hyperuricemia.

PMID- 24929541
TI  - Prevalence of colorectal carcinoma in CKD patients in pre-dialysis and during the
      dialysis introduction period.

PMID- 24929542
TI  - Decreased accumulation of cadmium in Drosophila selected for resistance suggests
      a mechanism independent of metallothionein.
AB  - Heavy metals, including cadmium, are common contaminants in environments subject
      to human activity. Responses to exposure in the fruit fly, Drosophila
      melanogaster, are dosage-dependent and resistance is selectable. While
      metallothionein-mediated sequestration has been extensively studied as a
      mechanism of cadmium resistance, a link between selection for resistance and an
      increased accumulation of cadmium has yet to be demonstrated. To address this
      need, we have selected wild-type flies for cadmium resistance for 20 generations
      and tested metal content using mass spectrometry. Resistant flies were observed
      to contain lower levels of cadmium, arguing for a mechanism of cadmium resistance
      that is not mediated by increased sequestration. This, coupled with genetic
      evidence suggesting the involvement of factors located on the X chromosome,
      suggests a gene other than metallothionein may be involved in resistance in this
      line. 

PMID- 24929543
TI  - Hepatoprotective effect of Arctium lappa root extract on cadmium toxicity in
      adult Wistar rats.
AB  - This study was performed to determine the effects of Arctium lappa (Al) to
      protect against cadmium damage in the rat liver. Male rats received a single i.p.
      dose of CdCl2 (1.2 mg/kg body weight (BW)) with or without Al extract
      administered daily by gavage (300 mg/kg BW) for 7 or 56 days. After 7 days, Al
      caused plasma transaminase activity to diminish in groups Al (glutamic
      oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) and CdAl
      (GPT). After 56 days, GOT and GPT plasma activities were reduced in the Cd group.
      No alteration in plasma levels of creatinine, total bilirubin, and total protein
      were observed. GOT liver activity increased in the Cd group. No alteration was
      observed in superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase
      (GST), and malondialdehyde (MDA) dosage. In the Cd group, hepatocyte proportion
      decreased and sinusoid capillary proportion increased. In the Al and CdAl groups,
      the nuclear proportion increased and the cytoplasmic proportion decreased. The
      hepatocyte nucleus density reduced in Cd and increased in the Al group. After 56
      days, there was no alteration in the Cd group. In Al and CdAl groups, the nuclear
      proportion increased without cytoplasmic proportion variation, but the sinusoid
      capillary proportion was reduced. The hepatocyte nucleus density decreased in the
      Cd group and increased in the Al and CdAl groups. In conclusion, the liver
      function indicators showed that A. lappa protected the liver against cadmium
      toxicity damage.

PMID- 24929544
TI  - Gene cloning, homology comparison and analysis of the main functional structure
      domains of beta estrogen receptor in Jining Gray goat.
AB  - To clarify the molecular evolution and characteristic of beta estrogen receptor
      (ERbeta) gene in Jining Gray goat in China, the entire ERbeta gene from Jining
      Gray goat ovary was amplified, identified and sequenced, and the gene sequences
      were compared with those of other animals. Functional structural domains and
      variations in DNA binding domains (DBD) and ligand binding domains (LBD) between
      Jining Gray goat and Boer goat were analyzed. The results indicate that the
      ERbeta gene in Jining Gray goat includes a 1584bp sequence with a complete open
      reading-frame (ORF), encoding a 527 amino acid (aa) receptor protein. Compared to
      other species, the nucleotide homology is 73.9-98.9% and the amino acid homology
      is 79.5-98.5%. The main antigenic structural domains lie from the 97th aa to the
      286th aa and from the 403rd aa to the 527th aa. The hydrophilicity and the
      surface probability of the structural domains are distributed throughout a range
      of amino acids. There are two different amino acids in the DBD and three
      different amino acids in the LBD between Jining Gray and Boer goats, resulting in
      dramatically different spatial structures for ERbeta protein. These differences
      may explain the different biological activities of ERbeta between the two goat
      species. This study firstly acquired the whole ERbeta gene sequence of Jining
      Gray goat with a complete open reading frame, and analyzed its gene evolutionary
      relationship and predicted its mainly functional structural domains, which may
      very help for further understanding the genome evolution and gene diversity of
      goat ERbeta. 

PMID- 24929545
TI  - In silico study of potential autoimmune threats from rotavirus infection.
AB  - Rotavirus, the major cause of infantile nonbacterial diarrhea, was found to be
      associated with development of diabetes-associated auto-antibodies. In our study
      we tried to find out further potential autoimmune threats of this virus using
      bioinformatics approach. We took rotaviral proteins to study similarity with Homo
      sapiens proteome and found most conserved structural protein VP6 matches at two
      regions with ryanodine receptor, an autoimmune target associated with myasthenia
      gravis. Myasthenia gravis, a chronic neurodegenerative autoimmune disorder with
      no typical known reason, is characterized by fluctuating muscle weakness which is
      typically enhanced during muscular effort. Affected patients generate auto
      antibodies against mainly acetyl choline receptor and sarcoplasmic reticulum
      calcium-release channel protein ryanodine receptor. Further, we observed that two
      regions which matched with ryanodine receptor remain conserved in all circulating
      rotaviral strains and showed significant antigenecity with respect to myasthenia
      gravis associated HLA haplotypes. Overall, our study detected rotaviral VP6 as a
      potential threat for myasthenia gravis and enlighten an area of virus associated
      autoimmune research. 

PMID- 24929546
TI  - Photochemical performance of thylakoid membrane in lead-treated Nymphoides
      peltatum.
AB  - Photochemical responses in the thylakoid membrane of Nymphoides peltatum to
      increasing lead (Pb) concentrations were investigated after 5 days of exposure.
      Pb accumulation increased in a concentration-dependent manner, with a maximum of
      118.44 MUg g(-1) at 100 MUM. Nutrients (Zn, Mg, Mo, Ca, Fe and Mn), ATPase
      activity and pigment generally increased progressively at Pb concentrations of
      12.5 and 25 MUM, but then declined at concentrations of 50 and 100 MUM. Moreover,
      Pb stress induced an increase in chlorophyll (Chl) a/b ratio in a different
      extent. No outstanding changes were observed in several Chl a fluorescence
      parameters at low Pb concentrations (12.5 and 25 MUM), while significant changes
      (p < 0.05) were observed in these parameters at higher concentrations. The
      alterations of nutrients, ATPase activity and pigment content were associated
      with disturbances in the thylakoid membrane, indicated by the quenching of Chl a
      fluorescence. These results were indicative of a disarray in photochemical
      activities exerted by Pb phytotoxicity.

PMID- 24929547
TI  - An emerging water contaminant, semicarbazide, exerts an anti-estrogenic effect in
      zebrafish (Danio rerio).
AB  - To determine the endocrine disrupting effect of semicarbazide, an emerging water
      contaminant, the changes in transcript levels of hepatic estrogen-response genes
      including vitellogenin-1 (vtg-1), estrogen receptor alpha (ERalpha), and estrogen
      receptor beta (ERbeta) were measured in male and female zebrafish exposed to
      semicarbazide with or without exogenous 17beta-estradiol (E2). Exposure of male
      zebrafish to semicarbazide for 96 h or 28 days resulted in no significant
      induction in hepatic vtg-1, ERalpha, or ERbeta mRNA expression, indicating that
      semicarbazide has no estrogenic effect. However, a remarkable anti-estrogenic
      effect of semicarbazide was demonstrated: semicarbazide treatment of female
      zebrafish for 96 h and 28 days resulted in significant decreases in transcript
      levels of vtg-1, ERalpha, and ERbeta, as well as decreases in the gonadosomatic
      index level after 28 days. Moreover, semicarbazide exposure significantly
      inhibited the induction of vtg-1, ERalpha and ERbeta mRNA by E2 when male
      zebrafish were co-exposed for 28 days.

PMID- 24929548
TI  - Comparing the effectiveness of video-assisted oral debriefing and oral debriefing
      alone on behaviors by undergraduate nursing students during high-fidelity
      simulation.
AB  - Complex healthcare, less resources, high-level medical equipment, and fewer
      available clinical settings have led many health professionals to use simulation
      as a method to further augment educational experiences for nursing students.
      While debriefing is recommended in the literature as a key component of
      simulation, the optimal format in which to conduct debriefing is unknown. This
      pre- and posttest two-group randomized quasi-experimental design compared the
      effectiveness of video-assisted oral debriefing (VAOD) and oral debriefing alone
      (ODA) on behaviors of 48 undergraduate nursing students during high-fidelity
      simulation. Further, this study examined whether roles (e.g., team leader,
      medication nurse), type of scenarios (i.e., pulmonary and cardiac scenarios), and
      student simulation team membership (i.e., VAOD and ODA groups) influenced these
      behaviors. Behaviors observed in this study related to patient safety,
      communication among team members, basic- and problem-focused assessment,
      prioritization of care, appropriate interventions, and delegation to healthcare
      team members. Both human patient simulator practice and guidance using video
      assisted oral debriefing and oral debriefing alone appeared to be comparable
      regarding behaviors, regardless of roles, type of scenarios, and student
      simulation team membership. These findings suggest that nurse educators may use
      either video-assisted oral debriefing or oral debriefing alone to debrief
      undergraduate nursing students during high-fidelity simulation. 

PMID- 24929549
TI  - Simultaneous determination of four volatile compounds in rat plasma after oral
      administration of Shexiang Baoxin Pill (SBP) by HS-SPDE-GC-MS/MS and its
      application to pharmacokinetic studies.
AB  - In this study, a headspace, solid-phase dynamic extraction method coupled to gas
      chromatography-tandem mass spectrometry (HS-SPDE-GC-MS/MS) method was developed
      for the simultaneous determination of four volatile compounds, namely,
      isoborneol, borneol, muscone and cinnamaldehyde, in rat plasma after oral
      administration of Shexiang Baoxin Pill (SBP) using naphthalene as an internal
      standard (IS). The target compounds were extracted using an SPDE needle device
      coated with a poly (dimethylsiloxane) (PDMS) phase. The detection was achieved by
      GC-MS/MS in multiple reaction monitoring (MRM) mode. The optimised mass
      transition ion pairs (m/z) for quantitation were 95.1/67.1 for isoborneol and
      borneol, 85.0/67.0 for muscone, 131.0/77.0 for cinnamaldehyde and 128.1/102.1 for
      the IS. The parameters that affect the extraction ratio, such as the pre
      incubation time, extraction temperature, number of extraction cycles, desorption
      volume and pH, were also optimised. The method was thoroughly validated with
      respect to specificity, linearity, precision, accuracy, recovery and stability. A
      sufficiently sensitive HS-SPDE-GC-MS/MS method was first developed in this study
      to determine the pharmacokinetics of volatile compounds found in rat plasma
      following oral administration of SBP. The method developed uses a simple
      procedure for plasma sample preparation and could be a promising tool for the
      analysis of complex volatile samples, such as traditional Chinese medicine (TCM).

PMID- 24929550
TI  - Simultaneous quantitative determination of microcystin-LR and its glutathione
      metabolites in rat liver by liquid chromatography-tandem mass spectrometry.
AB  - The roles of glutathione (GSH) and cysteine (Cys) in the detoxification of
      Microcystin-LR (MC-LR) have recently become a popular area of research. However,
      lacking analysis methods for MC-LR-GSH and MC-LR-Cys (two main GSH pathway
      metabolites) in mammals, elucidation of the detoxification mechanism and
      metabolic pathway of MC-LR in mammals is difficult. In this study, a novel method
      for the simultaneous quantitative analysis of MC-LR, MC-LR-GSH and MC-LR-Cys in
      rat liver was developed and validated. The analytes were simultaneously extracted
      from rat liver using 3M sodium chloride solution containing 0.01M EDTA-Na2-5%
      acetic acid, followed by solid-phase extraction (SPE) on Oasis HLB and silica
      cartridges and determination by liquid chromatography-electrospray ionization
      mass spectrometry (LC-ESI-MS/MS). Under the optimized pretreatment conditions and
      instrument parameters, good recoveries of MC-LR, MC-LR-GSH and MC-LR-Cys were
      obtained at three concentrations (0.2, 1.0 and 2.5 MUg g(-1) dry weight (DW))
      with values ranging from 97.7 +/- 4.2 to 98.7 +/- 5.1%, 70.1 +/- 4.8 to 71.1 +/-
      4.1% and 79.8 +/- 3.5 to 81.4 +/- 4.0%, respectively. The relative standard
      deviations (RSDs) of these compounds at 0.2, 1.0 and 2.5 MUg g(-1) DW were
      between 4.3% and 6.9%. The limits of detection (LODs) were 0.005, 0.007 and 0.006
      MUg g(-1) DW and the limits of quantification (LOQs) were 0.017, 0.023 and 0.020
      MUg g(-1) DW for MC-LR, MC-LR-GSH and MC-LR-Cys, respectively. Furthermore, this
      method was successfully applied to both time- and dosage-effect studies of MC-LR,
      MC-LR-GSH and MC-LR-Cys in vivo.

PMID- 24929551
TI  - Development and validation of high liquid performance chromatography-tandem mass
      spectrometry method for simultaneous determination of geniposidic acid and
      aucubin in rat plasma for pharmacokinetic study after oral administration of Du
      zhong tea extract.
AB  - A specific and sensitive high performance liquid chromatography coupled with
      tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for the
      simultaneous determination of geniposidic acid and aucubin in rat plasma after
      oral administration of Du-zhong tea extract. The plasma samples were pretreated
      by protein precipitation with methanol and the chromatographic separation was
      performed on a Hypersil C18 column (4.6 mm*250 mm, 5 MUm), using a gradient
      mobile phase system of water-methanol (0.05% formic acid). The detection was
      accomplished by multiple-reaction monitoring (MRM) scanning via electrospray
      ionization source operating in the negative ionization mode. The linear range was
      1-1,000 ng/mL for geniposidic acid and 0.2-200 ng/mL for aucubin, respectively.
      The accuracy (relative error, R.E.%) were between -5.40 and 5.00%, while the
      intra-day and inter-day precisions were less than 7.95 and 7.87% for the two
      analytes, respectively. The method was fully validated for the sensitivity,
      selectivity, recovery, matrix effect and stability. Then this method was
      successfully applied to the pharmacokinetic study of geniposidic acid and aucubin
      after oral administration of Du-zhong tea extract to rats and the results
      indicated that this HPLC-MS/MS assay is a valuable method for the pharmacokinetic
      study of geniposidic acid and aucubin in rat plasma.

PMID- 24929552
TI  - Annual input fluxes and source identification of trace elements in atmospheric
      deposition in Shanxi Basin: the largest coal base in China.
AB  - Industrialization and urbanization have led to a great deterioration of air
      quality and provoked some serious environmental concerns. One hundred and five
      samples of atmospheric deposition were analyzed for their concentrations of 13
      trace elements (As, Cd, Cu, Fe, Al, Co, Cr, Hg, Mn, Mo, Pb, Se, and Zn) in Shanxi
      Basin, which includes six isolate basins. The input fluxes of the trace elements
      in atmospheric deposition were observed and evaluated. Geostatistical analysis
      (EF, PCA, and CA ) were conducted to determine the spatial distribution, possible
      sources, and enrichment degrees of trace elements in atmospheric deposition.
      Fe/Al and K/Al also contribute to identify the sources of atmospheric deposition.
      The distribution of trace elements in atmospheric deposition was proved to be
      geographically restricted. The results show that As, Cd, Pb, Zn, and Se mainly
      come from coal combustion. Fe, Cu, Mn, Hg, and Co originate mainly from
      interactions between local polluted soils and blowing dust from other places,
      while the main source of Al, Cr, and Mo are the soil parent materials without
      pollution. This work provides baseline information to develop policies to control
      and reduce trace elements, especially toxic elements, from atmospheric
      deposition. Some exploratory analytical methods applied in this work are also
      worth considering in similar researches.

PMID- 24929553
TI  - Disorder-specific functional abnormalities during temporal discounting in youth
      with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD
      and Autism.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder
      (ASD) are often comorbid and share cognitive abnormalities in temporal foresight.
      A key question is whether shared cognitive phenotypes are based on common or
      different underlying pathophysiologies and whether comorbid patients have
      additive neurofunctional deficits, resemble one of the disorders or have a
      different pathophysiology. We compared age- and IQ-matched boys with non-comorbid
      ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls
      (18) using functional magnetic resonance imaging (fMRI) during a temporal
      discounting task. Only the ASD and the comorbid groups discounted delayed rewards
      more steeply. The fMRI data showed both shared and disorder-specific
      abnormalities in the three groups relative to controls in their brain-behaviour
      associations. The comorbid group showed both unique and more severe brain
      discounting associations than controls and the non-comorbid patient groups in
      temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral
      striatum and anterior cingulate, suggesting that comorbidity is neither an
      endophenocopy of the two pure disorders nor an additive pathology. 

PMID- 24929554
TI  - Mini-FLOTAC, Kato-Katz and McMaster: three methods, one goal; highlights from
      north Argentina.
AB  - BACKGROUND: Copro-parasitological diagnosis is still a challenge in management of
      helminth infections at individual and community levels in resource-limited
      settings.The aim of our study was to compare the performance of three
      quantitative techniques: Kato-Katz, McMaster and Mini-FLOTAC methids. The study
      was carried out in Oran, Northern Argentina. METHODS: 200 schoolchildren were
      enrolled to provide a single stool sample, which was tested for helminth
      infections with Kato-Katz, McMaster and Mini-FLOTAC methods. The Mini-FLOTAC was
      performed with two flotation solutions (FS2 saturated saline and FS7 zinc
      sulphate). Preparation and reading time for each of the three methods was
      calculated both when processing single and multiple samples. RESULTS: Out of 193
      schoolchildren examined, 40% were positive for any helminth infection by any
      method; the most prevalent was Hymenolepis nana (23%) followed by Ascaris
      lumbricoides (17%) and a third group of less prevalent helminths: Enterobius
      vermicularis, Trichuris trichiura and hookworms (11% all together). Mini-FLOTAC
      FS2 was more sensitive than FS7 for H. nana (93% vs 78%) and for other helminths
      (85% vs 80%), whereas FS7 was more sensitive for A. lumbricoides (87% vs 61%).
      Kato-Katz method was more sensitive than McMaster method for A. lumbricoides (84%
      vs 48%) and for other helminths (48% vs 43%) except for H. nana (49% vs 61%). As
      for egg counts, Mini-FLOTAC FS2 reported 904 eggs per gram of faeces (EPG) for H.
      nana (vs 457 with McMaster and 111 with Kato-Katz) and 1177 EPG for A.
      lumbricoides (vs 1315 with Kato-Katz and 995 with McMaster); FS2 detected the
      highest EPG for both H.nana and A.lumbricoides (904 vs 568 and 1177 vs 643
      respectively), the differences were not statistically significant. The technique
      feasibility was calculated: Kato-Katz mean time was 48 minutes/sample, Mini
      FLOTAC 13 minutes/sample and McMaster 7 minutes/sample. However, especially for
      Kato-Katz and Mini-FLOTAC, the mean time (min/sample) decreased significantly
      when processing multiple samples. CONCLUSIONS: Mini-FLOTAC is a promising
      technique for helminth diagnosis, it is more sensitive than Kato-Katz and
      McMaster for H. nana and as sensitive as Kato-Katz and more sensitive than
      McMaster for A. lumbricoides identification. Egg counts differences although
      relevant, did not reach statistical significance.

PMID- 24929555
TI  - Macrophages regulate renal fibrosis through modulating TGFbeta superfamily
      signaling.
AB  - Renal fibrosis is the fundamental pathway leading to end-stage renal disease,
      while its exact molecular basis remains incompletely elucidated. Previous studies
      have demonstrated that transforming growth factor beta 1 (TGFbeta1) is an inducer
      of the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial
      cells, while bone morphogenic protein 7 (BMP7) counteracts TGFbeta1-induced EMT
      and reverses chronic renal injury. Although macrophage recruitment is believed to
      play an important role during the whole pathogenesis, the mechanism underlying
      their activate involvement in the formation of renal fibrosis besides
      phagocytosizing extracellular matrix and apoptotic cells is largely unknown.
      Here, in a mouse unilateral ureteral obstruction (UUO) model, we show that the
      recruited macrophages are mainly M1 macrophages at early stage. However, these
      F4/80-positive and CD301-negative M1 macrophages were shortly polarized into
      F4/80-positive and CD301-positive M2 macrophages, respectively, which released
      high levels TGFbeta1, to contradict the local expression of BMP7 to facilitate
      EMT-induced renal fibrosis. M2 macrophages depletion specifically inhibited EMT,
      and subsequently the renal fibrosis. Adoptive transplantation of M2 macrophages
      increased the features of renal fibrosis. Our study thus identified double-edged
      effects of macrophages in the formation of renal fibrosis, which suggest that
      modulation of macrophage polarization may substantially improve the treatment of
      renal fibrosis. 

PMID- 24929556
TI  - Malnutrition in pregnancy following bariatric surgery: three clinical cases of
      fetal neural defects.
AB  - OBJECTIVE: Bariatric surgery results in decreased food intake and a variable
      degree of malabsorption. Without adequate supplementation, the most common
      complications of this surgery are nutritional disorders. Pregnancy following
      surgery for obesity is a particular condition requiring strict monitoring of
      nutrient intake necessary for fetal development and a favourable neonatal
      prognosis. PATIENTS: Malnutrition in pregnancy and congenital neural
      malformations are reported in three women who had previously undergone bariatric
      surgery (1, 5 and 18 years before pregnancy, respectively). Two patients
      underwent the Roux en Y bypass and one bilio-pancreatic diversion with
      gastroplasty. None of the three received pre-conceptional nutritional
      counselling. Patients 1 and 2 did not undergo postoperative nutritional
      surveillance; nutrient supplementation was started at 22 and 20 weeks gestation,
      respectively. In patient 3, supplementation was stopped at six weeks gestation.
      RESULTS: Newborns 1 and 2 presented with dorsal myelomeningocele and ventricular
      dilation. Both underwent surgery and a ventriculo-peritoneal shunt was inserted
      in the first month of life. Newborn 3 had microcephaly, bilateral microphthalmia
      and sensorineural deafness. CONCLUSIONS: Diet and nutritional status, before and
      during pregnancy, play an important role in the early processes of fetal
      development and neonatal outcome. Women of childbearing age who have had
      bariatric surgery, should be encouraged to follow a well-balanced diet as part of
      a weight management strategy. They should be advised to take recommended maternal
      supplements.

PMID- 24929557
TI  - Self-sacrificial behavior and its explanation in terms of Max Scheler's concept
      of spirit.
AB  - One of the key concepts of the German philosopher Max Scheler (1874-1928) is his
      concept of spirit. He understands spirit as one of several naturally functioning
      human mental agencies, such as consciousness, will, memory, etc. That is, he
      treats the mental agency of spirit in a scientific way and avoids any esoteric or
      religious connotations that this peculiar term may involve. The nature of human
      spirit, according to Scheler, is the ability to withstand and deliberately
      redirect biological imperatives and instinctive drives, up to the point of
      purposefully throwing away one's own life. The presence of spirit constitutes the
      essence of the human being that differentiates him qualitatively from all
      animals. In this article, I argue that it is human spirit that plays the
      determinative role in causing heroic and self-sacrificial behavior. I also argue
      that the individual human spirit experiences its inherent development, thus
      having several rather dissimilar stages and manifestations. I discuss the meaning
      that the term 'spirit' has in the English and the American philosophical and
      psychological traditions and the meaning of the corresponding term 'der Geist' in
      the German traditions. The specific English-language understanding of the term
      'spirit', compared to its German counterpart 'der Geist', namely, less scientific
      and more religious and esoteric and metaphorical for the former, makes it alien
      and almost unusable in the English and American traditions. The linguistic
      difference leads to the misunderstanding of some very important ideas brought by
      the concept of spirit as introduced by Scheler. My purpose is to overcome this
      discrepancy and omission and to introduce the notion and the concept of spirit,
      in their scientific understanding, into the arsenal of modern English-language
      cognitive science, psychology, and philosophy in order to provide for the full
      explanatory force of the hitherto neglected concept of spirit. 

PMID- 24929558
TI  - Localization of Epileptogenic Zone on Pre-surgical Intracranial EEG Recordings:
      Toward a Validation of Quantitative Signal Analysis Approaches.
AB  - In patients diagnosed with pharmaco-resistant epilepsy, cerebral areas
      responsible for seizure generation can be defined by performing implantation of
      intracranial electrodes. The identification of the epileptogenic zone (EZ) is
      based on visual inspection of the intracranial electroencephalogram (IEEG)
      performed by highly qualified neurophysiologists. New computer-based quantitative
      EEG analyses have been developed in collaboration with the signal analysis
      community to expedite EZ detection. The aim of the present report is to compare
      different signal analysis approaches developed in four different European
      laboratories working in close collaboration with four European Epilepsy Centers.
      Computer-based signal analysis methods were retrospectively applied to IEEG
      recordings performed in four patients undergoing pre-surgical exploration of
      pharmaco-resistant epilepsy. The four methods elaborated by the different teams
      to identify the EZ are based either on frequency analysis, on nonlinear signal
      analysis, on connectivity measures or on statistical parametric mapping of
      epileptogenicity indices. All methods converge on the identification of EZ in
      patients that present with fast activity at seizure onset. When traditional
      visual inspection was not successful in detecting EZ on IEEG, the different
      signal analysis methods produced highly discordant results. Quantitative analysis
      of IEEG recordings complement clinical evaluation by contributing to the study of
      epileptogenic networks during seizures. We demonstrate that the degree of
      sensitivity of different computer-based methods to detect the EZ in respect to
      visual EEG inspection depends on the specific seizure pattern.

PMID- 24929559
TI  - New perspectives on the mismatch negativity (MMN) component: an evolving tool in
      cognitive neuroscience.

PMID- 24929560
TI  - A novel Ca2+-activated, thermostabilized polyesterase capable of hydrolyzing
      polyethylene terephthalate from Saccharomonospora viridis AHK190.
AB  - Only two polyethylene glycol terephthalate (PET)-degrading enzymes have been
      reported, and their mechanism for the biochemical degradation of PET remains
      unclear. To identify a novel PET-degrading enzyme, a putative cutinase gene
      (cut190) was cloned from the thermophile Saccharomonospora viridis AHK190 and
      expressed in Escherichia coli Rosetta-gami B (DE3). Mutational analysis indicated
      that substitution of Ser226 with Pro and Arg228 with Ser yielded the highest
      activity and thermostability. The Ca(2+) ion enhanced the enzyme activity and
      thermostability of the wild-type and mutant Cut190. Circular dichroism suggested
      that the Ca(2+) changes the tertiary structure of the Cut190 (S226P/R228S), which
      has optimal activity at 65-75  degrees C and pH 6.5-8.0 in the presence of 20 %
      glycerol. The enzyme was stable over a pH range of 5-9 and at temperatures up to
      65  degrees C for 24 h with 40 % activity remaining after incubation for 1 h at
      70  degrees C. The Cut190 (S226P/R228S) efficiently hydrolyzed various aliphatic
      and aliphatic-co-aromatic polyester films. Furthermore, the enzyme degraded the
      PET film above 60  degrees C. Therefore, Cut190 is the novel-reported PET
      degrading enzyme with the potential for industrial applications in polyester
      degradation, monomer recycling, and PET surface modification. Thus, the Cut190
      will be a useful tool to elucidate the molecular mechanisms of the PET
      degradation, Ca(2+) activation, and stabilization.

PMID- 24929561
TI  - Study of seed hair growth in Populus tomentosa, an important character of female
      floral bud development.
AB  - BACKGROUND: Poplar seed hair is an environmental annoyance in northern China due
      to its abundance and widespread airborne distribution after maturation. The
      morphogenesis and molecular mechanisms of its development are not well
      understood, and little attention has been focused on the dynamics of its
      development. To better understand the mechanism of poplar seed hair development,
      paraffin sections were used to examine the initiation and elongation of poplar
      seed hairs. RNA-seq technology was also employed to provide a comprehensive
      overview of transcriptional changes that occur during seed hair development.
      RESULTS: The placenta at the base of ovary, was identified as the origin of seed
      hair development, which is in sharp contrast to cotton fibers that originate from
      epidermal cells of the seed coat. An enlarged cell nucleus in seed hair cells was
      also observed, which was supported by our gene ontology enrichment analysis. The
      significant enriched GO term of "endoreduplication" indicated that cycles of
      endoreduplication, bypassing normal mitosis, is the underlying mechanisms for the
      maintenance of the uni-cellular structure of seed hairs. By analyzing global
      changes in the transcriptome, many genes regulating cell cycle, cell elongation,
      cell well modification were identified. Additionally, in an analysis of
      differential expression, cellulose synthesis and cell wall biosynthesis-related
      biological processes were enriched, indicating that this component of fiber
      structure in poplar seed hairs is consistent with what is found in cotton fibers.
      Differentially expressed transcription factors exhibited a stage-specific up
      regulation. A dramatic down-regulation was also revealed during the mid-to-late
      stage of poplar seed hair development, which may point to novel mechanisms
      regulating cell fate determination and cell elongation. CONCLUSIONS: This study
      revealed the initiation site of poplar seed hairs and also provided a
      comprehensive overview of transcriptome dynamics during the process of seed hair
      development. The high level of resolution on dynamic changes in the transcriptome
      provided in this study may serve as a valuable resource for developing a more
      complete understanding of this important biological process.

PMID- 24929562
TI  - Causes of death in patients with extranodal cancer of unknown primary: searching
      for the primary site.
AB  - BACKGROUND: Cancer of unknown primary (CUP) is a fatal cancer, accounting for 3
      5% of all diagnosed cancers. Finding the primary site is important for
      therapeutic choices and we believe that the organ which is designated as the
      cause of death may give clues about the primary site. METHODS: A total of 20,570
      patients with CUP were identified from the Swedish Family-Cancer Database. Causes
      of death--as reported in the death certificate--were investigated, analyzing
      reported metastatic sites and histological subtypes separately. Survival was
      compared with metastatic cancer with a known primary tumor. RESULTS: An organ
      specific cancer could be identified as a cause of death in approximately 60% of
      all CUP patients with adenocarcinoma or undifferentiated histology. In
      adenocarcinoma, lung cancer was the most frequent cause of death (20%), followed
      by pancreatic cancer (14%), and ovarian cancer (11%). Lung cancer was the most
      common cause of death in patients with CUP metastases diagnosed in the nervous
      system (69%), respiratory system (53%), and bone (47%), whereas ovarian cancer
      was the most common cause of death when CUP was diagnosed in the pelvis (47%) or
      the peritoneum (32%). In CUP diagnosed in the liver, liver and pancreatic cancers
      accounted for 26% and 22% of deaths, respectively. Also in squamous cell CUP,
      lung cancer was the most common cause of death (45%). CONCLUSIONS: According to
      the causes of death, the primary site appeared frequently to be either the organ
      where CUP metastases were diagnosed or an organ which may be traced through the
      known metastatic patterns of different cancer types.

PMID- 24929563
TI  - Survey and online discussion groups to develop a patient-rated outcome measure on
      acceptability of treatment response in vitiligo.
AB  - BACKGROUND: Vitiligo is a chronic depigmenting skin disorder which affects around
      0.5-1% of the world's population. The outcome measures used most commonly in
      trials to judge treatment success focus on repigmentation. Patient-reported
      outcome measures of treatment success are rarely used, although recommendations
      have been made for their inclusion in vitiligo trials. This study aimed to
      evaluate the face validity of a new patient-reported outcome measure of treatment
      response, for use in future trials and clinical practice. METHOD: An online
      survey to gather initial views on what constitutes treatment success for people
      with vitiligo or their parents/carers, followed by online discussion groups with
      patients to reach consensus on what constitutes treatment success for individuals
      with vitiligo, and how this can be assessed in the context of trials.
      Participants were recruited from an existing database of vitiligo patients and
      through posts on the social network sites Facebook and Twitter. RESULTS: A total
      of 202 survey responses were received, of which 37 were excluded and 165
      analysed. Three main themes emerged as important in assessing treatment response:
      a) the match between vitiligo and normal skin (how well it blends in); b) how
      noticeable the vitiligo is and c) a reduction in the size of the white patches.
      The majority of respondents said they would consider 80% or more repigmentation
      to be a worthwhile treatment response after 9 months of treatment. Three online
      discussion groups involving 12 participants led to consensus that treatment
      success is best measured by asking patients how noticeable their vitiligo is
      after treatment. This was judged to be best answered using a 5-point Likert
      scale, on which a score of 4 or 5 represents treatment success. CONCLUSIONS: This
      study represents the first step in developing a patient reported measure of
      treatment success in vitiligo trials. Further work is now needed to assess its
      construct validity and responsiveness to change.

PMID- 24929564
TI  - Rayleigh wave scattering from a vertical edge of isotropic substrates.
AB  - The paper numerically studies the harmonic Rayleigh wave scattering at the 90
      degree corner of isotropic substrate. The finite element method is used. The main
      attention is paid to two cases. The first one is the apex of the substrate corner
      is rounded off. The second one consists in that a layer of foreign material is
      deposited on the face which scatters the Rayleigh wave. The dependence of the
      reflection and the transmission coefficients on the Poisson ratio, the angle of
      incidence, the fillet radius, and the layer thickness are obtained. It is found
      that if the Rayleigh wave is incident perpendicularly to the substrate border,
      then the fillet of small radius as compared to the wavelength increases the
      reflection coefficient and decreases the transmission coefficient by factors 1.3
      1.8. At normal incidence, the Poisson ratio does not change qualitatively the
      dependence of the reflection and transmission coefficients on the fillet radius.
      But the Poisson ratio can substantially affect the angle dependence of these
      coefficients if the wave is incident obliquely on the corner rounded off. It is
      also found out that a layer can modify the conditions of scattering such that the
      incident wave is totally reflected without transmission and conversion into bulk
      waves in a wide interval of angle of incidence, although, in principle, the bulk
      wave generation is allowed within a part of this angle interval. 

PMID- 24929565
TI  - Leprosy in the South Pacific.

PMID- 24929566
TI  - Allowing violence in New Zealand hospitals is bad business.

PMID- 24929567
TI  - Patient aggression experienced by staff in a New Zealand public hospital setting.
AB  - AIMS: Working in a healthcare environment is a known risk factor for violence.
      Patient aggression towards staff is often present in a hospital setting but the
      extent, type and variation among various occupations and roles are not known.
      METHOD: This research examines the type and frequency of aggression experienced
      by healthcare staff, using a previously used measure the POPAS-NZ, which is a
      short pen and paper survey. Responses were gathered from 227 people working in a
      single district health board. RESULTS: Responses showed verbal anger was
      experienced by 93% of healthcare workers in the previous year and physical
      aggression was experienced by 65% of respondents. Also, 38% of staff reported
      experiencing a physical assault in the previous year. When analysed by role it
      was found that nurses and support staff experienced the greatest number of
      aggressive incidents compared to doctors and allied health staff. No effects of
      gender of the healthcare worker were found. Psychiatric units showed greater
      levels of destructive behaviour and attempted assaults but were similar to other
      areas of the hospital on all other measures. CONCLUSION: These results
      demonstrate many hospital staff, of all roles and workplaces experience
      aggression on a frequent basis. Implications for staff training are discussed.

PMID- 24929568
TI  - Why do patients self-present to Middlemore Hospital Emergency Department?
AB  - AIM: To determine the drivers for acute (Australasian Triage Scale Category 3-5)
      demand in patients who self-present to New Zealand's Middlemore Hospital
      Emergency Department (MMH ED), we sought to establish a demographic profile of a
      sample of self-presenting patients and explore their reasons for presenting to ED
      rather than attending a primary care centre. METHOD: A prospective, observational
      study was undertaken of patients in Australasian Triage Scale Categories 3-5 (ATS
      3-5) who self-presented to MMH ED over a 7 day period from 14 April 2011 to 21
      April 2011. We studied two time periods, 0900-1200 and 1800-2200, to compare
      drivers for attendance to MMH ED during primary care service open hours and
      closed hours. A structured questionnaire was used to collect demographic data and
      outcomes. The cumulative 2011 demographic data for self-presentations to MMH was
      compared to the study data. RESULTS: 500 patients were approached to participate
      and 421 met the inclusion criteria. The mean age of presenters was 37.6 years (SD
      of 24.6) with 48.2% (95%CI 44-53%) being male and 23% (95%CI 19-27%) employed. Of
      those who indicated they had a general practitioner (GP), 23% (95%CI 21-30%) had
      contacted their GP prior to presentation to MMH ED, with 73% (n=73) advised to
      attend ED. Of the 73 patients told by their GP to attend ED, 30 (41.1%; 95%CI 31
      53%) were admitted, with two patients being transferred to another district
      health board (DHB), and the remainder discharged home. Thirty-two percent of the
      self-presenting patients came to ED because they felt sick enough to require
      emergency care. Comparison of the data for the two time periods indicated only
      one significant difference: 14% of patients presented to ED in the morning
      because their GP was closed, whereas 28.7% of those who presented after hours did
      so for this reason. CONCLUSION: Almost 25% of self-presenting patients had
      contacted their GP or a health professional prior to their ED presentation and
      were advised to attend ED. The most common reason for patients to self-present at
      MMH ED is the belief that a hospital emergency department is the appropriate
      service to treat acute sickness. Neither cost nor knowledge of the Shorter Stays
      in Emergency Departments Health Target featured as a reason for attendance.

PMID- 24929569
TI  - Premature mortality in adults using New Zealand psychiatric services.
AB  - AIMS: People with experience of mental illness, in particular those accessing
      mental health services, have increased mortality compared to the general
      population, but no studies have examined the situation in New Zealand. This study
      uses a complete national dataset to estimate mortality rates from natural and
      external causes for adults using psychiatric services compared to the general New
      Zealand population. METHODS: Routinely collected data on adults aged 18-64 using
      secondary mental health services between January 2002 and December 2010 were
      linked to death registrations over the same period. Indirect standardisation was
      used to estimate the mortality ratio (SMR) for those with any contact with mental
      health services over this period compared to the New Zealand population. RESULTS:
      Both men and women using mental health services in New Zealand have more than
      twice the mortality rate of the total population [combined SMR 2.14 (95% CI 2.09
      2.19)], with an increased risk of death from cancer and cardiovascular disease
      [SMRs=1.31(1.24-1.37), and 1.69 (1.60-1.79) respectively], and external causes
      (suicide and accidents) [SMR 3.11 (3.00-3.23)]. People with a diagnosis of a
      psychotic disorder had three times the overall death rate of the population.
      CONCLUSIONS: This study confirms that those using mental health services in New
      Zealand are dying prematurely from both natural and external causes, and provides
      evidence which supports calls for coordinated action on this issue.

PMID- 24929570
TI  - Risk factors for general medicine readmissions and association with mortality.
AB  - AIMS: To investigate general medicine readmissions for risk factors and
      association with mortality. METHOD: A case control study was performed comparing
      the characteristics of 30-day general medicine patients readmitted between 1
      January to 30 June 2012 to a general medicine service at Capital and Coast
      District Health Board (Wellington region, New Zealand) with an equal number of
      randomly selected patients not readmitted to the service during the same time
      period. RESULTS: 197 patients discharged from general medicine were readmitted
      during the 6-month study period. There were no differences in the sex, ethnicity,
      residential care at admission, history of dementia, length of admission or
      weekend discharge of readmitted patients compared to non-readmitted patients. The
      mean age, number of medications and comorbidities score were higher in the
      readmission group. Readmission (even after controlling for age, polypharmacy, and
      comorbidities) was a strong predictor of 1-year all-cause mortality, with an odds
      ratio of 2.2. Twenty-one percent of readmission patients had more than one
      general medicine readmission, up to 30 days between each, with even higher
      mortality rate compared to one readmission (49% vs. 28%). CONCLUSION: Readmission
      to general medicine is strongly associated with older age, polypharmacy, and
      multiple comorbidities. Readmission is an independent strong risk factor for 1
      year mortality, with this risk increasing after multiple readmissions.
      Readmissions can be a marker of deteriorating patient's condition, and a
      discussion in relation to prognosis, ceiling of treatment, resuscitation status
      documentation and advance directive may be warranted.

PMID- 24929571
TI  - Does seasonal level of serum 25-OH vitamin D correlate with the activity of
      Crohn's disease?
AB  - BACKGROUND AND AIM: Vitamin D has immune modulating effects and normal to high
      levels might be correlated with less severe Crohn's disease (CD). We aimed to
      review seasonal vitamin D levels in CD patients in correlation with disease
      activity. METHODS: CD patients were identified from an inflammatory bowel disease
      (IBD) database and given two questionnaires enquiring about vitamin D
      supplementation, sun exposure, sunblock application and symptoms to complete the
      CDAI. Participants were examined and serum 25-OH vitamin D [25(OH)D] levels and
      haematocrit were determined in winter (06/2011-09/2011) and summer (12/2011
      03/2012). Patients taking vitamin D supplements or with extensive small bowel
      resection were excluded. RESULTS: 32 patients (19 women, mean age 39 plus or
      minus 16 years, range 18-73 years), from Dunedin, New Zealand (45 degrees 52' S,
      170 degrees 30' E) consented to participate in the study. Of these, three took
      vitamin D supplements and were excluded. In winter 76% of the participants had
      serum 25(OH)D levels classified as deficient (<50 nmol/L) and all of them had
      insufficient 25(OH)D levels (<75 nmol/L). In summer, serum 25(OH)D levels were
      deficient only in 10% but insufficient in 55% of the participants. Mean serum
      25(OH)D level was 35.9 nmol/L (norm 50-150nmol/L) in winter (range 5-67, SD 17.5)
      and 69.6 nmol/L in summer (range 13-119, SD 19.0) (p<0.0005). There was no
      significant difference in the seasonal levels of serum 25(OH)D between male and
      female participants (p=0.601). Mean CDAI score was 103.9 in winter (range -10
      262, SD 76.9) and 90.2 in summer (range -13-331, SD 84.0) (p=0.365). A mixed
      effects regression analysis showed no statistically significant correlation
      between seasonal levels of serum 25(OH)D and CDAI (p=0.612) among our study
      participants. CONCLUSION: Suboptimal levels of serum 25(OH)D were found in the
      majority of our study participants particularly in winter and they would benefit
      from supplementation. Our study showed no statistically significant correlation
      between seasonal serum 25(OH)D levels and CD activity. Given the limitations of
      the study, the role of 25(OH)D as a predictor of disease activity could not be
      clearly concluded.

PMID- 24929572
TI  - From ICU to hospital-wide: extending central line associated bacteraemia (CLAB)
      prevention.
AB  - AIMS: To decrease hospital-wide central line associated bacteraemia (CLAB) by
      spreading the prevention programme beyond the intensive care unit (ICU) in a
      secondary care hospital in Auckland, New Zealand. METHOD: Over 15 months, four
      general surgical wards, five inpatient units, and surgical theatres adopted the
      quality improvement initiative, and were followed for a further 15 months. The
      initiative included central line insertion and maintenance checklists, a central
      line insertion pack, training in central line care, and a dedicated database. In
      addition, a checklist to assess the readiness of each new area was developed;
      data collection and analysis processes embedded, with rapid feedback to staff and
      in-depth review of all CLAB events. RESULTS: Compliance measures improved
      significantly (compliance with insertion increased from a mean of 84% to 92%
      p=0.001; maintenance from 64% to 85%, p=0.002). The absolute numbers of CLAB fell
      hospital-wide from a mean of 2.3/month to 0.56/month. The rate of CLAB hospital
      wide decreased from 7.04/1,000 line days to 1.37/1,000. CONCLUSION: We have
      demonstrated that the CLAB prevention work proven effective in the ICU can be
      successfully adapted and expanded to the rest of the hospital. As central lines
      are increasingly inserted in units outside the ICU, and maintained in general
      wards, this work provides some useful insights into tackling this larger problem.

PMID- 24929573
TI  - Rising antimicrobial resistance: a strong reason to reduce excessive
      antimicrobial consumption in New Zealand.
AB  - Steadily rising rates of antimicrobial resistance, in a range of common bacterial
      pathogens, are a major threat to human health in New Zealand in the near future.
      The single largest contributor to this threat is the high level of antimicrobial
      consumption in New Zealand. Antimicrobial consumption in New Zealand needs to be
      reduced if we are to slow the spread of antimicrobial-resistant bacteria.
      Reporting the per capita antimicrobial consumption within each District Health
      Board (DHB), in relation to targets for reductions from present levels of
      consumption, could provide an impetus for DHBs to address this threat to the
      health of their populations. 

PMID- 24929574
TI  - Endocrine encephalopathy.
AB  - The diagnosis of Hashimoto's encephalopathy is made when no other cause is found
      for an acute encephalopathic illness, in the presence of positive thyroid
      autoantibodies, and is supported by a response to steroid therapy. A 59-year
      woman developed an encephalopathic illness with mixed aphasia, global weakness
      and generalised seizures requiring intubation and ICU admission. Extensive
      imaging and laboratory investigations looking for an underlying cause for the
      encephalopathy were unremarkable. Thyroid autoantibodies were strongly positive,
      raising the possibility of Hashimoto's encephalopathy. Thyroid function testing
      showed profound primary hypothyroidism. The patient was commenced on high-dose
      methyprednisolone, with prompt cessation of seizure activity. Thyroxine
      replacement was commenced, with the methyprednisolone switched to oral prednisone
      and slowly weaned. The patient had no further seizures and ultimately made a full
      recovery. 

PMID- 24929575
TI  - Medical image. A benign glossal lesion. Geographic tongue.

PMID- 24929576
TI  - The leprosy problem in the South Pacific.

PMID- 24929577
TI  - Chewing the saturated fat: should we or shouldn't we?

PMID- 24929578
TI  - Performance of funded point-of-care capillary blood glucose meters at altitude.

PMID- 24929579
TI  - Improving functional annotation for industrial microbes: a case study with Pichia
      pastoris.
AB  - The research communities studying microbial model organisms, such as Escherichia
      coli or Saccharomyces cerevisiae, are well served by model organism databases
      that have extensive functional annotation. However, this is not true of many
      industrial microbes that are used widely in biotechnology. In this Opinion piece,
      we use Pichia (Komagataella) pastoris to illustrate the limitations of the
      available annotation. We consider the resources that can be implemented in the
      short term both to improve Gene Ontology (GO) annotation coverage based on
      annotation transfer, and to establish curation pipelines for the literature
      corpus of this organism. 

PMID- 24929580
TI  - Microparticle, nanoparticle, and stem cell-based oxygen carriers as advanced
      blood substitutes.
AB  - Here, we discuss recent advances in the development of artificial red blood cell
      (RBC) substitutes, illustrating lessons learned from initial attempts using
      perfluorocarbon (PFC) emulsions and acellular hemoglobin-based oxygen carriers
      (HBOCs). We also highlight novel oxygen-containing microparticles, nanoparticles,
      and stem cell-derived RBC products, with emphasis on improvements in
      biocompatibility and oxygen delivery. In addition, we envision future
      developments for the rational design of advanced blood substitutes that aim to
      address unmet clinical needs. 

PMID- 24929581
TI  - Expression pattern of porcine antimicrobial peptide PR-39 and its induction by
      enterotoxigenic Escherichia coli (ETEC) F4ac.
AB  - PR-39 is a gene-encoded, proline-arginine-rich porcine antimicrobial peptide with
      multiple biological functions. In the current study, the tissue-specific mRNA
      expression of PR-39 was investigated in Chinese Jinhua pigs, and the effect of
      enterotoxigenic Escherichia coli (ETEC) expressing F4ac (K88ac) fimbriae
      challenge on the mRNA expression of PR-39 in various tissues was compared between
      Jinhua and Landrace pigs. The three most stable expressed housekeeping genes were
      validated before evaluating PR-39 expression. PR-39 mRNA was predominantly
      expressed in the bone marrow compared with the spleen, thymus, MLN, liver and
      ileum. The ETEC F4ac challenge could up-regulate PR-39 mRNA expression in both
      Jinhua and Landrace pigs, but the changes were different between the two breeds.
      Jinhua pigs responded more strongly to ETEC F4ac challenge than did Landrace
      pigs, because the interaction between the breed and challenge significantly
      impact PR-39 mRNA in the thymus, liver and ileum. The PR-39 mRNA expression
      levels of challenged Jinhua pigs were significantly higher in the spleen, thymus,
      liver, ileum and MLN compared with challenged Landrace pigs. These differences in
      the mRNA expression of PR-39 could be a result of genetic differences in the
      resistance to ETEC F4ac infection between the two breeds, but this speculation
      requires further investigation. 

PMID- 24929582
TI  - A launching pad.

PMID- 24929583
TI  - The moment of opportunity.

PMID- 24929584
TI  - Common risk factors in the management of periodontal and associated systemic
      diseases: the dental setting and interprofessional collaboration.
AB  - There is a role for dentistry in the interprofessional management of chronic
      diseases by addressing common risk factors BACKGROUND: A critical scientific
      foundation has developed for management of risk factors common to major diseases
      including periodontal disease, caries, diabetes, heart disease, and cancer.
      PURPOSE: The purpose of this paper is to critically review this scientific
      literature. This will provide the basis for the current and future role of the
      dental setting in common risk factor identification and modification; with an
      emphasis on the role of the dental hygienist. METHODS: A systematic review of the
      literature and analysis of the relevant papers was undertaken to support the
      recommendations. CONCLUSIONS: We propose that the appropriate risk factor
      management procedures be adopted in the dental setting for smoking cessation,
      reduction of sugar consumption, and weight control in those patients at risk for
      one or a combination of the following diseases: periodontal disease, caries,
      diabetes, heart disease and certain cancers.

PMID- 24929586
TI  - Saliva and biofilm-based diagnostics: a critical review of the literature
      concerning sialochemistry.
AB  - There is some evidence to support the use of salivary diagnostics in dentistry.
      BACKGROUND AND PURPOSE: The use of saliva as a diagnostic fluid has the potential
      to shape the role of oral health care professionals in the health care system.
      While more than a handful of chairside diagnostic tests are available for use by
      private practitioners, the evidence supporting their use continues to emerge.
      METHODS: An electronic search of the literature indexed on the PubMed electronic
      database was conducted to identify human clinical trials utilizing commercially
      available salivary diagnostics. Papers meeting the inclusion criteria, and any
      applicable references were critically appraised following SORT guidelines.
      CONCLUSIONS: While the literature concerning salivary analysis is continuously
      growing, the limited literature that is available doesn't focus on patient
      oriented health outcomes. This 'infant' literature is focused on validating
      metrics and identifying biomarkers with diagnostic potential. As such, the
      evidence level of the literature is graded as level 3. Despite the lower grade,
      the research in this area shows consistent results, coherent conclusions, and
      research identifying new biomarkers will provide additional dimensions to
      salivary diagnostics.

PMID- 24929585
TI  - Obesity and cumulative inflammatory burden: a valuable risk assessment parameter
      in caring for dental patients.
AB  - A new model of risk assessment that recognizes the importance of reducing
      patients' cumulative inflammatory burden by targeting overweight and obesity, in
      individuals with periodontal disease, may be a valuable risk assessment parameter
      in caring for dental patients. BACKGROUND: The growing body of evidence that
      suggests obesity, Metabolic Syndrome and periodontal disease are interrelated
      offers an unprecedented opportunity to adopt a new model of risk assessment that
      has the potential to beneficially influence not only the periodontal health of
      obese and overweight patients, but simultaneously may also reduce a person's
      overall risk for developing heart disease and type 2 diabetes, and perhaps other
      inflammatory driven disease states. METHODS: This paper presents an overview of
      research that builds the case for a new model of risk assessment that focuses on
      the cumulative inflammatory burden that may be elevated by the presence of
      periodontal disease in obese patients. In addition, the biological plausibility
      of the concepts of inflammatory priming and inflammatory loading is discussed,
      and several simple ideas are suggested for identifying at-risk patients.
      CONCLUSIONS: Given the significant rise in obesity and the impact that obesity
      has on periodontal health and other inflammatory driven, systemic disease states,
      adoption of a new model of risk assessment is suggested-one that considers an
      individual's cumulative inflammatory burden which may be amplified as a result of
      coexisting obesity and other components of Metabolic Syndrome and periodontal
      disease. Knowledge gathered thus far combined with further clinical research must
      be translated into better ways to treat and maintain obese periodontal patients.
      These measures may pave the way for prevention of metabolic diseases and obesity
      with a relevant impact on patients' periodontal status.

PMID- 24929587
TI  - Periodontal debridement: still the treatment of choice.
AB  - Periodontal debridement (PD) remains a gold standard for the treatment of
      inflammatory periodontitis. BACKGROUND/PURPOSE: The evidence base regarding the
      causal relationship between oral biofilm and the host inflammatory response to
      the etiology of periodontal disease has substantially increased over the years.
      What has not changed significantly during that time is the conservative manner in
      which the disease can be treated with periodontal debridement (PD). Since dental
      hygienists, in particular, specialize in providing these procedures it is
      important to evaluate the evidence that supports periodontal debridement as a
      primary and fundamental treatment modality. METHOD: An extensive narrative
      literature review that included systematic reviews, examined traditional PD, the
      use of adjuncts to enhance PD and newer PD procedures to determine what are the
      best practices for achieving optimal clinical outcomes. CONCLUSION: Compared to
      surgical therapy, PD results in maintenance of attachment levels over time, but
      is not as effective in the initial reduction of probing depths in deep pockets.
      Sustained release local drug delivery agents have some modest adjunctive effects
      when used with PD, as do systemic antibiotics in aggressive periodontitis cases.
      Reported analyses of the long term effects of chemotherapeutic agents usually do
      not extend beyond a few months to a year. While laser therapy is still under
      investigation it remains as a potential PD therapy. New instruments being refined
      to better visualize the root surface either non-surgically or with mini papilla
      reflection flaps, hold promise for the future when they become more affordable
      and accessible. Despite the development of new technology, it still appears that
      periodontal debridement (PD) remains the gold standard for the treatment of
      inflammatory periodontitis.

PMID- 24929588
TI  - Periodontal regeneration: management of periodontal osseous defects by the
      periodontist-dental hygienist team.
AB  - Periodontal health can be restored through assessment, diagnosis, treatment and
      management of periodontal osseous defects by the periodontist-dental hygienist
      team. BACKGROUND AND PURPOSE: Treatment of periodontitis has evolved over time,
      with regenerative periodontal therapy at the forefront in cutting-edge
      periodontal care. While the techniques and materials available today are allowing
      therapists to push the limits of periodontal regeneration and achieve success in
      increasingly more difficult cases, the principles of successful regeneration
      remain the same. Case selection, identification and resolution of etiologic and
      contributing factors, proper surgical technique, follow-up and patient education
      are keys to obtaining a successful outcome. The impact of the dental hygienist in
      assessment and maintenance is highlighted. METHODS: Literature review of the key
      research studies evaluating the etiology and contributing factors in the
      development osseous defects, osseous defect and tooth-related characteristics,
      and principles of successful regenerative therapy. The authors draw upon their
      experience with patient care and clinical research to synthesize the evidence
      relevant to today's dental hygienist. CONCLUSIONS: Periodontal regeneration is a
      well-supported and predictable therapy that can be utilized to restore
      periodontal support and health. The dental hygienist is key in assessing and
      caring for the periodontal health of patients over time. Identifying who may
      benefit from regenerative periodontal therapy is an essential skill for today's
      practicing dental hygienist.

PMID- 24929589
TI  - Management of peri-implant disease: a current appraisal.
AB  - While the clinical science of managing peri-implant diseases is progressing,
      careful monitoring and preventive care of peri-implant tissue health during
      maintenance is paramount. BACKGROUND: Implants have become a routine treatment
      option for missing dentition. The biological complications of restored dental
      implants and associated supra-structures share similarities with the biofilm
      infections of natural dentition. Our existing paradigms of periodontal disease
      treatment can partially be applied to management of peri-implant disease.
      APPROACH: A critical analysis of the peri-implant disease literature was
      conducted, anchored by a search on the MEDLINE database (2005 to present) by way
      of Ovid Medline((r)). Search terms peri-implantitis, peri-implant mucositis and
      peri-implant diseases were utilized. Select references within bibliographies of
      review articles were sought. CONCLUSION: The dental team must play a critical
      role in educating patients to control plaque-biofilm associated with peri-implant
      tissues and associated restorations. Routine assessments at maintenance
      appointments allow early treatment intervention to prevent escalation of peri
      implant disease. Given the infancy of clinical science surrounding peri
      implantitis treatment, further, high-quality evidence based studies are expected.

PMID- 24929590
TI  - Mechanical self-performed oral hygiene of implant supported restorations: a
      systematic review.
AB  - A systematic review of self-performed oral hygiene practices for optimal
      maintenance of dental implant-supported restorations reveals a lack of evidence
      to support best practices. BACKGROUND: The standard of the patients' home care is
      a key factor for long term stability of dental implants and the prevention of
      biological complications. The objective of this systematic review is to evaluate
      and summarize the literature with respect to various mechanical oral hygiene
      modalities around implant-supported restorations. METHODS: MEDLINE, Cochrane
      CENTRAL and EMBASE databases were searched up to October 2013 to identify
      eligible studies. Five studies that met the inclusion criteria were included. Two
      cohort studies about powered toothbrushes and three (randomized) controlled
      trials comparing powered to manual toothbrushes were reviewed. All studies showed
      an improvement in the clinical parameters over time. Powered toothbrushes were
      found to perform better than manual toothbrushes but no firm conclusions can be
      made between treatment modalities. CONCLUSIONS: There is a lack of evidence with
      respect to effective and optimal self-performed oral hygiene around dental
      implants. At present, home care recommendations are based on the knowledge that
      is available with respect to cleaning of natural teeth. It becomes evident that
      there is an urgent need for academic institutions and industry to initiate and
      support high quality randomized controlled clinical trials on this topic in the
      near future.

PMID- 24929591
TI  - Tooth whitening: what we now know.
AB  - Current research about tooth whitening shows that it is safe and effective when
      manufacturer's protocol is followed, yet there are risks of which the profession
      and users should be aware. This update provides a summary of current research and
      assessment of the safety and efficacy of tooth whitening regimens. BACKGROUND:
      Tooth whitening has become one of the most frequently requested dental procedures
      by the public. The public has come to demand whiter, more perfect smiles and in
      response many choices for tooth whitening have been made available. These include
      home-based products such as toothpastes, gels, and films, as well as in-office
      based systems where products containing highly concentrated bleaching agents are
      applied under professional supervision. The profession and public have been aware
      of certain risks related to tooth whitening such as increased tooth sensitivity
      and gingival irritation. New research has shown that there are other risks such
      as tooth surface roughening and softening, increased potential for
      demineralization, degradation of dental restorations, and unacceptable color
      change of dental restorations. The new research is also focused on optimizing
      whitening procedures to reduce tooth sensitivity and to increase the persistence
      of the whitening. METHODS: Current reports in the literature are reviewed that
      are related to the use of peroxide based whitening methods. These reports include
      in vitro studies for method optimization and mechanism as well as clinical
      studies on effects of various whitening regimens. CONCLUSIONS: When
      manufacturer's instructions are followed, hydrogen peroxide and carbamide
      peroxide based tooth whitening is safe and effective. Patients should be informed
      of the risks associated with tooth whitening and instructed on identification of
      adverse occurrences so that they may seek professional help as needed.

PMID- 24929592
TI  - A best practices approach to caries management.
AB  - Caries management by risk assessment represents best practices and is an evidence
      based model that focuses on treating and preventing disease at the patient level
      rather than a surgical/restorative approach at the tooth level. BACKGROUND:
      Dental caries is a multifactorial, biofilm and pH mediated disease that affects
      people of all ages and disproportionally affects certain populations at epidemic
      proportions. Simply restoring cavitated teeth does nothing to resolve the
      disease. At the heart of the CAMBRA philosophy is identifying the patient's
      unique risk level for future caries disease. This can be done by completing a
      caries risk assessment (CRA). Several easy to use CRA questionnaires are
      available. Once the patient's unique risk level has been determined, preventive
      and therapeutic interventions, based on the specific risk level, can then be
      implemented. METHODS: Landmark publications, original research, and systematic
      reviews are analyzed and reviewed to form the basis for this shift in patient
      care related to caries disease. CONCLUSIONS: Caries management by risk assessment
      has emerged as the new paradigm in patient care and represents an evidence-based,
      best practices approach with the potential for significant advantages over
      traditional methods.

PMID- 24929593
TI  - Risk management strategies for reducing oral adverse drug events.
AB  - Oral adverse drug effects negatively impact oral health, comfort and function.
      BACKGROUND: Patients treated in the oral health care environment take multiple
      medications, many of which cause oral complications. Dental professionals are
      challenged with making recommendations to prevent or minimize drug-induced oral
      disease risks, while reducing symptoms to improve oral health quality of life.
      METHODS: This paper presents a critical analysis of current evidence regarding
      common oral adverse drug events, and reviews existing clinical practice
      guidelines based upon findings from published systematic reviews. RESULTS: There
      is a lack of sufficient, high quality evidence to support most recommendations
      for interventions to relieve signs and symptoms of drug-induced oral adverse
      events. Existing recommendations are largely based on data obtained from
      observational studies and case reports, and from randomized controlled clinical
      trials with significant design flaws and potential reporting bias. Outcome
      measures, especially those related to symptom relief and long-range benefits, are
      either insufficient or lacking. CONCLUSIONS: Oral adverse drug effects are a
      common problem, and additional data is needed to support best practices for
      product recommendations to improve oral health in medicated patients.

PMID- 24929595
TI  - Dental hygiene intervention to prevent nosocomial pneumonias.
AB  - Nosocomial and ventilator associated pneumonias that plague critically ill,
      elderly and long-term care residents could be reduced with effective oral hygiene
      practices facilitated collaboratively between nurses and dental hygienists.
      BACKGROUND: Nosocomial pneumonias, specifically aspiration pneumonias and
      ventilator-associated pneumonias in the elderly and infirm have become a major
      health care issue, The provision of oral care in hospital and hospital-like
      facilities presents challenges that can prevent patients from receiving optimal
      oral care One sequela can be aspiration pneumonia which ranks first in mortality
      and second in morbidity among all nosocomial infections. Since aspiration
      pneumonia is linked to the colonization of oral bacteria in dental plaque and
      biofilm, it is time to look for creative solutions to integrating the expertise
      of dental hygienists into health care teams in these institutional settings.
      METHODS: A comprehensive review of the literature was conducted regarding the
      etiology and prevalence of health care related pneumonias. Evidence describing
      the challenges and barriers that the nurses, nursing staff, and dental hygienists
      face in the provision of oral care in hospitals and long-term care facilities is
      provided. Intercollaborative solutions to providing optimal oral care in
      hospitals and long-term care facilities are suggested. CONCLUSION: Dental
      hygienists have the expertise and practice experience to provide oral care in
      hospitals, long-term care and residential facilities. They can contribute to
      solving oral care challenges through intercollaboration with other health care
      team members. Yet, there are long-standing systemic barriers that must be
      addressed in order to provide this optimal care. Dental hygienists becoming
      better assimilated within the total health care team in hospital and residential
      facilities can positively impact the suffering, morbidity and mortality
      associated with aspiration pneumonias.

PMID- 24929594
TI  - Focus on fluorides: update on the use of fluoride for the prevention of dental
      caries.
AB  - Improving the efficacy of fluoride therapies reduces dental caries and lowers
      fluoride exposure. BACKGROUND: Fluoride is delivered to the teeth systemically or
      topically to aid in the prevention of dental caries. Systemic fluoride from
      ingested sources is in blood serum and can be deposited only in teeth that are
      forming in children. Topical fluoride is from sources such as community water,
      processed foods, beverages, toothpastes, mouthrinses, gels, foams, and varnishes.
      The United States Centers for Disease Control and Prevention (CDC) and the
      American Dental Association (ADA) have proposed changes in their long standing
      recommendations for the amount of fluoride in community drinking water in
      response to concerns about an increasing incidence of dental fluorosis in
      children. Current research is focused on the development of strategies to improve
      fluoride efficacy. The purpose of this update is to inform the reader about new
      research and policies related to the use of fluoride for the prevention of dental
      caries. METHODS: Reviews of the current research and recent evidence based
      systematic reviews on the topics of fluoride are presented. Topics discussed
      include: updates on community water fluoridation research and policies; available
      fluoride in dentifrices; fluoride varnish compositions, use, and recommendations;
      and other fluoride containing dental products. This update provides insights into
      current research and discusses proposed policy changes for the use of fluoride
      for the prevention of dental caries. CONCLUSIONS: The dental profession is
      adjusting their recommendations for fluoride use based on current observations of
      the halo effect and subsequent outcomes. The research community is focused on
      improving the efficacy of fluoride therapies thus reducing dental caries and
      lowering the amount of fluoride required for efficacy.

PMID- 24929596
TI  - Autism spectrum disorders: an update on oral health management.
AB  - Dental professionals caring for patients with a diagnosis of autism spectrum
      disorder (ASD) will need to provide oral health care based on a family-centered
      approach that involves a comprehensive understanding of parental concerns and
      preferences, as well as the unique medical management, behaviors, and needs of
      the individual patient. BACKGROUND: With the rising prevalence of autism spectrum
      disorders (ASD), oral health providers will find themselves increasingly likely
      to care for these patients in their daily practice. The purpose of this article
      is to provide a comprehensive update on the medical and oral health management of
      patients with autism spectrum disorders. METHODS: The authors conducted a
      literature review by searching for relevant articles written in English in the
      PubMed database pertaining to the medical and oral health management of autism,
      including caries status, preventive, behavioral, trauma, and restorative
      considerations. CONCLUSIONS: A detailed family centered approach based on
      parental preferences and concerns, the patient's challenging behaviors, and
      related comorbidities can serve to improve the treatment planning and oral health
      management of dental patients with ASD.

PMID- 24929597
TI  - Under the influence: informing oral health care providers about substance abuse.
AB  - Treating the drug addicted dental patient is different than treating the non
      addicted patient due to differences related to the
      emotional/behavioral/personality issues of the addict, the addict's often poor
      general health and poor nutrition, ongoing problems of oral hygiene and the
      effects of drugs on the oral mucosa, gingiva and dentition BACKGROUND: Oral
      health care providers need to be aware of the emerging trends in substance abuse,
      able to recognize patient's addicted to drugs and to be knowledgeable about the
      effects of substance abuse to provide the most efficacious treatment to avoid the
      consequences of contraindicated dental procedures and therapy. This article
      defines the scope of the problem of drug abuse and provides an overview of
      commonly abused substances and their effects on health and oral health. METHODS:
      A review of the literature combined with the authors' extensive experience in the
      substance abuse field explains parameters of oral health care treatment of the
      drug addicted individual for patient and provider safety. CONCLUSIONS: The drug
      culture has evolved and the drug user is different. Oral health care providers
      need to realize that any patient may be an addict in order to identify them,
      provide appropriate oral care and direct them, if they desire, toward appropriate
      treatment.

PMID- 24929598
TI  - Confronting human papilloma virus/oropharyngeal cancer: a model for
      interprofessional collaboration.
AB  - A collaborative practice model related to Human Papilloma Virus (HPV) associated
      oropharyngeal cancer highlights the role of the dental hygienist in addressing
      this condition. BACKGROUND: The incidence of HPV associated head and neck cancer
      is rising. Multiple professionals including the dental hygienist can work
      collaboratively to confront this growing public health concern. METHODS: A
      critical review applies the growth and utilization of interprofessional education
      (IPE) and interprofessional collaboration (IPC) to multi-disciplinary models
      addressing the human papilloma virus and oropharyngeal cancers. CONCLUSIONS: A
      model related to HPV associated oropharyngeal cancer addresses an oral systemic
      condition that supports the inclusion of a dental hygienist on collaborative
      teams addressing prevention, detection, treatment and cure of OPC.

PMID- 24929599
TI  - Proliferative verrucous leukoplakia: an elusive disorder.
AB  - Proliferative Verrucous Leukoplakia (PVL) is a multifocal form of progressive
      leukoplakia with a high rate of malignant transformation that requires early
      recognition by oral health care providers for proper management. BACKGROUND AND
      PURPOSE: PVL will frequently appear as an innocuous white lesion or lesions that
      can easily be overlooked or considered clinically insignificant, yet it has a
      high rate of malignant transformation. There is limited in-depth knowledge about
      the pathobiology of PVL. Oral health care providers lack familiarity with this
      lesion; consequently the intent of this article is to increase awareness of the
      clinical aspects of PVL. METHODS: Case reports, case series and review articles
      provide a profile of PVL. CONCLUSION: It is essential that health care providers
      performing intraoral examinations are aware that PVL is a distinct and rare form
      of multifocal oral leukoplakia. PVL commonly affects females above the age of 62.
      Currently, little is known about its etiopathogenesis. Additionally, no specific
      treatment modality has proven to be effective in aborting its progression.
      Because of its high recurrence potential and relentless progression to squamous
      cell carcinoma, all recurrent and multifocal white lesions of the oral cavity
      should be viewed with suspicion.

PMID- 24929600
TI  - Laser technology to manage periodontal disease: a valid concept?
AB  - Present day dental lasers can create oral environments conducive for periodontal
      repair. BACKGROUND AND PURPOSE: With the bacterial etiology of periodontitis and
      the resulting host inflammatory reaction, clinicians continue to search for
      therapeutic modalities to assist in the non-surgical management of periodontal
      disease. Traditional chairside therapies consist of mechanical debridement with
      manual and/or ultrasonic instrumentation with the objective of removing calculus,
      biofilm, and endotoxin from tooth root surfaces. Decreasing the microbial stimuli
      and associated end products decreases the inflammatory reaction and allows the
      host an opportunity to regenerate tissue through wound healing. The purpose of
      this article is to examine whether dental lasers, which have been in use for the
      past 3 decades, may augment traditional non-surgical periodontal therapy.
      METHODS: Review of research publications related to lasers and non-surgical
      periodontics with attention focused on systematic studies. CONCLUSIONS: Studies
      utilizing laser technology may demonstrate positive effects on 1) selectively
      decreasing the biofilm environment, 2) removing calculus deposits and
      neutralizing endotoxin, 3) removing sulcular epithelium to assist in reattachment
      and decreased pocket depth, and 4) biostimulation for enhanced wound healing.
      Comparisons of studies to determine the difference between lasers and their
      respective effects on the periodontium are difficult to assess due to a wide
      variation of laser protocols.

PMID- 24929601
TI  - Health disparities and the multicultural imperative.
AB  - Providing culturally and linguistically appropriate care is a crucial step toward
      the elimination of oral health disparities in the United States. BACKGROUND:
      Health disparities, coupled with rapidly changing demographic trends, continue to
      plague healthcare, the health care workforce and population health. Consequently,
      there is still more work indicated to ensure individuals, regardless of race or
      ethnicity, receive quality health care at an affordable price. The purpose of
      this paper is to increase the awareness of oral health care practitioners about
      the causes and consequences of oral health disparities and to highlight promising
      strategies aimed at improving effective communication between health care
      providers and the patients they serve. METHODS: A narrative utilizing key
      publications will explain the concept of the multicultural imperative, and its
      direct relationship to the elimination of health disparities including oral
      health disparities. CONCLUSIONS: It is essential that oral health professionals
      strive to become culturally and linguistically proficient in communicating with
      and caring for all our patients. Members of professional organizations and
      academic institutions can also work to ensure that both students and current
      practitioners have access to a curriculum and continuing education with the
      intended outcome of increased cultural proficiency.

PMID- 24929602
TI  - Expanding oral care opportunities: direct access care provided by dental
      hygienists in the United States.
AB  - Dental hygienists expand access to oral care in the United States. BACKGROUND:
      Many Americans have access to oral health care in traditional dental offices
      however millions of Americans have unmet dental needs. For decades dental
      hygienists have provided opportunities for un-served and under-served Americans
      to receive preventive services in a variety of alternate delivery sites, and
      referral to licensed dentists for dental care needs. METHODS: Publications, state
      practice acts, state public health departments, the American Dental Hygienists'
      Association, and personal interviews of dental hygiene practitioners were
      accessed for information and statistical data. RESULTS: Dental hygienists in 36
      states can legally provide direct access care. Dental hygienists are providing
      preventive services in a variety of settings to previously un-served and under
      served Americans, with referral to dentists for dental needs. CONCLUSION: Dental
      hygienists have provided direct access to care in the United States for decades.
      The exact number of direct access providers in the United States is unknown.
      Limited research and anecdotal information demonstrate that direct access care
      has facilitated alternate entry points into the oral health systems for thousands
      of previously un-served and underserved Americans. Older adults, persons with
      special needs, children in schools, pregnant women, minority populations, rural
      populations, and others have benefited from the availability of many services
      provided by direct access dental hygienists. Legislatures and private groups are
      becoming increasingly aware of the impact that direct access has made on the
      delivery of oral health care. Many factors continue to drive the growth of direct
      access care. Additional research is needed to accumulate qualitative and
      quantitative outcome data related to direct access care provided by dental
      hygienists and other mid level providers of oral health services.

PMID- 24929603
TI  - Are dental hygienists prepared to work in the changing public health environment?
AB  - Health care reform, the changing public health environment, and a lack of clarity
      about what defines a 'public health professional' create challenges as well as
      opportunities for dental hygienists who wish to pursue positions or careers in
      public health. BACKGROUND: Although many studies have been conducted about dental
      hygienists in clinical practice, there are few describing dental hygienists
      working in public health positions, particularly in non-clinical roles, or how
      well their education and other resources prepared them for these roles.
      Competency statements and the 10 Essential Public Health Services to Promote Oral
      Health in the U.S. provide a public health framework to assess what skills will
      be required for future opportunities that may emerge for dental hygienists.
      METHODS: Published literature, recent unpublished survey data, selected
      professional health care reform documents, competency statements, accreditation
      standards, and the 10 Essential Public Health Services to Promote Oral Health in
      the U.S. were analyzed. Competencies in public health/dental public health
      provide an overview of skills needed by dental hygienists who will be seeking
      public health positions. Health reform statements describe the need for more
      leadership and workforce models in public health, while the 10 Essential Services
      can serve as a framework for career preparation/transition. CONCLUSIONS: The
      literature does not provide a comprehensive historical review or current profile
      of dental hygienists who work in various public health positions or their various
      roles, especially non-clinical roles. More research is needed regarding current
      positions, degree and experience requirements, and role responsibilities.
      Additionally, the credentials and public health background of the faculty
      teaching community/public health courses in dental hygiene programs requires
      exploration. Follow-up studies of dental hygiene program graduates could help
      determine how well courses prepare students for public health activities or
      careers and what resources aid in transitioning from clinical to public health
      positions. Dental hygienists need more information about education, continuing
      education and employment opportunities related to pursuing a career in public
      health.

PMID- 24929604
TI  - Elder's oral health crisis.
AB  - Dentistry must prepare to meet the challenges of providing oral health services
      to the increasing numbers of medically compromised and cognitively impaired older
      adults whose care is often complicated by functional, behavioral, and situational
      factors. BACKGROUND: With the unprecedented aging of the population, oral health
      care providers will be treating a greater number of older adults than in the
      past. There will also be a larger frail and vulnerable cohort with physical
      and/or cognitive conditions, disabilities and limited financial resources. The
      elderly suffer disproportionately from oral disease and limited access to oral
      health care. Many older adults are either unwilling or unable to receive routine
      care, putting them at greater risk for general and oral complications. Some
      present with extensive oral disease, the cumulative effects of disease throughout
      their lifetime, an even more complicated situation when frail elders are
      homebound or in long-term care institutions. To care optimally for this aging
      cohort, oral health professionals need to be knowledgeable about the many
      conditions, disabilities and age-related changes associated with aging. METHODS:
      Literature review and discussion of the key research studies describing
      demographic and societal changes leading to the current multifactorial oral
      health care crisis impacting older adults. The authors draw upon the evidence and
      their experience in geriatric patient care to provide information relevant to
      today's oral health care practitioners treating older adults. CONCLUSION: Oral
      health services are an essential component of primary geriatric health care. The
      growing population of older and impaired adults requires practitioners who are
      sensitive to the myriad of functional, behavioral and situational factors that
      impact this aged cohort. Adequate access to quality oral health care for the aged
      is a salient public health issue that will require political and psychobiomedical
      interprofessional collaboration to adequately address.

PMID- 24929605
TI  - Teledentistry: a key component in access to care.
AB  - Teledentistry has the potential to address the oral care needs of those who have
      limited access to care. More research is needed to establish the evidence base to
      support teledentistry practice. BACKGROUND AND PURPOSE: Enormous potential exists
      to improve oral health services throughout the world by using information and
      communication technologies, such as teledentistry to expand access to primary,
      secondary and tertiary care. Comparison of teledentistry procedures with standard
      clinical procedures can demonstrate the relative effectiveness and cost of each
      approach. However, due to insufficient evidence, it is unclear how these
      strategies compare for improving and maintaining oral health, quality of life,
      and reducing health care costs. This review discusses the merits of teledentistry
      for the delivery of oral care. METHODS: This article summarizes the available
      literature related to the efficacy and effectiveness of teledentistry and
      presents possible barriers to its broader adoption. CONCLUSIONS: Teledentistry
      seems to be a promising path for providing oral health services where there is a
      shortage of oral health care providers.

PMID- 24929606
TI  - Advancing education in dental hygiene.
AB  - The changing health care environment and societal imperatives indicate the need
      for transformative change within the dental hygiene profession to serve the
      emerging needs of the public. The American Dental Hygienists' Association is
      leading the way toward meaningful change. BACKGROUND AND PURPOSE: The American
      Dental Hygienists' Association (ADHA) has as its vision the integration of dental
      hygienists into the health care delivery system as essential primary care
      providers to expand access to oral health care. This article provides data on
      current dental hygiene education programs and those in development. Also included
      is a discussion regarding how the dental hygiene profession can better serve the
      health and wellness needs of society by transforming the way graduates are
      prepared for the future. METHOD: ADHA's dental hygiene survey center data,
      policies and a futuristic analysis plus a review of the professional literature
      describe the current state of dental hygiene education and the profession. A
      discussion of societal, health care and educational trends that creates the
      imperative for transformation of the dental hygiene profession is provided.
      CONCLUSIONS: Ultimately, the purpose of advancing education in dental hygiene is
      to achieve better oral and overall health for more people. The profession's
      responsibility to the public includes evaluating its own ability to provide care
      and taking the steps necessary to ensure its maximum effectiveness. ADHA is
      leading this process for dental hygienists in diverse ways. It is imperative that
      the dental hygiene profession understands and embraces the changing health care
      environment. Through open dialog and the sharing of evidence the professional
      path will be determined along with forward movement for the benefit of society
      and the dental hygiene profession.

PMID- 24929607
TI  - Empowerment through mentorship and leadership.
AB  - Leadership is vital to future growth and change in the dental hygiene profession.
      BACKGROUND AND PURPOSE: As health care reform emerges, state practice acts expand
      and new models of dental hygiene practice are created and implemented, dental
      hygienists will assume leadership positions that may be quite different from the
      more traditional leadership roles they assume today. These dental hygienist
      leaders will envision, creatively design and implement oral health care programs
      to improve the oral health of the public. Mentoring, a vital component of
      leadership development, is critical for dental hygienists to acquire knowledge,
      guidance, and growth. METHODS: This paper provides a literature-supported
      overview of leadership and mentoring principles applicable to dental hygienists
      in their personal and professional lives. Opportunities for dental hygienists to
      assume leadership roles are also described. CONCLUSIONS: Dental hygienists are
      poised to become leaders and vital members of the professional team promoting and
      integrating oral health care as a part of general health. Consequently, the
      dental hygienist's leadership roles are likely to expand and can be strengthened
      through mentoring relationships and mentoring teams. Ultimately, this can
      increase professional growth and career satisfaction for the dental hygienist as
      well as improve oral health care for the public.

PMID- 24929608
TI  - Dental hygiene and research: irrevocably connected.
AB  - Although remarkable growth has occurred in the dental hygiene research arena, an
      increased emphasis on research development will facilitate the designation of
      dental hygiene as a true discipline. BACKGROUND: Dental hygienists have
      participated in research for nearly 100 years. Support for research development
      has increased due to contributions of the American Dental Hygienists' Association
      and other grant monies that have funded seminal educational endeavors to elevate
      the research skills of dental hygienists. Dental hygiene initiated research
      endeavors, the advent of doctoral degree programs in dental hygiene, expansion of
      the dental hygiene body of knowledge, and efforts toward interprofessional
      collaboration continue to elevate the profession of dental hygiene while
      addressing the oral health needs of the public. METHODS: The research focus in
      dental hygiene is reviewed. Landmark events that have supported research
      endeavors are described and examples of historically important global
      contributions made by dental hygienists are chronicled. CONCLUSIONS: Further
      development of a body of dental hygiene research will help position the
      profession alongside other academically recognized health care disciplines. A
      small, dedicated group of dental hygienists have worked toward advancing the
      profession in this way, but additional growth is essential if dental hygiene is
      to be considered a true discipline. One such initiative on the near horizon is
      the doctoral degree in dental hygiene.

PMID- 24929609
TI  - Critical thinking in patient centered care.
AB  - Health care providers can enhance their critical thinking skills, essential to
      providing patient centered care, by use of motivational interviewing and evidence
      based decision making techniques. BACKGROUND AND PURPOSE: The need for critical
      thinking skills to foster optimal patient centered care is being emphasized in
      educational curricula for health care professions. The theme of this paper is
      that evidence-based decision making (EBDM) and motivational interviewing (MI) are
      tools that when taught in health professions educational programs can aid in the
      development of critical thinking skills. This paper reviews the MI and EBDM
      literature for evidence regarding these patient-centered care techniques as they
      relate to improved oral health outcomes. METHODS: Comparisons between critical
      thinking and EBDM skills are presented and the EBDM model and the MI technique
      are briefly described followed by a discussion of the research to date.
      CONCLUSIONS: The evidence suggests that EBDM and MI are valuable tools; however,
      further studies are needed regarding the effectiveness of EBDM and MI and the
      ways that health care providers can best develop critical thinking skills to
      facilitate improved patient care outcomes.

PMID- 24929610
TI  - Technology is a critical game changer to the practice of dental hygiene.
AB  - Dental hygienists will need to embrace 21st century technology to adapt to
      workplace settings. BACKGROUND AND PURPOSE: To stay relevant in the workforce,
      dental hygienists need mastery of new skills and technologies. The purpose of
      this paper is to elucidate the vast array of technological advances impacting
      dental practice and the consequent implications for oral health care providers.
      CRITICAL ANALYSIS: New technologies have provided unparalleled opportunities for
      degree and career advancement for dental hygienists. Advances in science and
      technology are providing patients with better quality and more convenient oral
      health care. Dental hygienists need technological skills that enable them to
      fully utilize technology as a strategy for consultation with dentists and other
      health care professionals and for other purposes. Continuing education and life
      long learning factor into preparing dental hygienists for 21st century
      technologies. CONCLUSION: With technological advances, less adaptive
      professionals could potentially see a decrease in demand for their services.
      Possessing a high level of knowledge of dentistry and dental hygiene does not
      ensure a position in the workforce. Knowledge of technologies and associated
      skills are required for quality patient care and career and personal growth.

PMID- 24929611
TI  - Pediatric burns in military hospitals of China from 2001 to 2007: a retrospective
      study.
AB  - BACKGROUND: Childhood burns are a global health problem. To date, no
      epidemiological study with a large sample size of hospitalized pediatric burn
      patients from the Chinese mainland has been conducted. This study retrospectively
      analyzed pediatric burn cases to identify the characteristics of pediatric burns
      and their risk factors in China. METHODS: Data for pediatric burn inpatients
      younger than 14 years were retrieved from the Chinese Trauma Databank (CTDB). The
      epidemiological characteristics of pediatric burns and risk factors for mortality
      were analyzed. RESULTS: A total of 61,068 cases were included in the study.
      Children under 3 years old were at the highest risk of injury. Scalds were the
      commonest burns (87.59%). Flame burns occurred more in winter, and electrical
      burns occurred mainly in July and August. Age, etiology, depth of injury, total
      body surface area (TBSA), site of injury, and outcome were correlated with length
      of hospital stay. Risk factors for pediatric burn mortality included being male,
      having third degree burns, >=30% TBSA, and having multi-site burns. CONCLUSION:
      The results showed the epidemiological characteristics of pediatric burns in
      China, which differ from those reported for other countries and regions. These
      characteristics can be used to develop measures to prevent pediatric burns.

PMID- 24929612
TI  - Effects of different unstable sole construction on kinematics and muscle activity
      of lower limb.
AB  - Unstable sole construction can change biomechanics of lower extremity as
      highlighted by some previous studies, which could potentially help developing
      special training or rehabilitation schemes. In this study, unstable elements are
      fixed in heel and forefoot zone to exert unstable perturbations, and the position
      changes (medial, neutral and lateral) of unstable elements in forefoot coronal
      plane are adjusted to analyze changes of lower extremity kinematics and muscle
      activities. Twenty-two healthy male subjects participated in the test, walking
      with control shoes and experimental shoes randomly under self-selected speed.
      Kinematics and surface electromyography measurements were carried out
      simultaneously. It is found that experimental shoes can lead to the reduction of
      knee abduction and internal rotation and hip internal rotation, with p<.05. Ankle
      inversion and internal rotation amplitude were also reduced, which are associated
      with significantly increased activation levels of muscles (TA-tibialis anterior,
      PL-peroneus longus, LG-lateral gastrocnemius) in order to compensate
      perturbations. It is suggested that a training equipment incorporating unstable
      elements would enhance postural control by adjusting lower extremity kinematics
      and reorganizing muscle activity. More research can be conducted to testify the
      feasibility of unstable shoes construction on human postural control and gait,
      even guide training regime design, injury prevention and rehabilitation. 

PMID- 24929613
TI  - Frequency and pattern of voluntary pedalling is influenced after one week of
      heavy strength training.
AB  - Changes in voluntary rhythmic leg movement characteristics of freely chosen
      cadence (reflecting movement frequency) and tangential pedal force profile
      (reflecting movement pattern) were investigated during 4weeks of (i) heavy hip
      extension strength training (HET, n=9), (ii) heavy hip flexion strength training
      (HFT, n=9), and (iii) no intervention (CON, n=9). Training consisted of three 5RM
      10RM sets per session, with two sessions/week. Submaximal ergometer cycling was
      performed before the training period (pretest) and after every week of training
      (test A1, A2, A3, and posttest). Strength increased by on average 25% in HET and
      33% in HFT. Freely chosen cadence was only changed in HET, occurring already
      after 1week of training. Thus, percentage reductions of cadence in HET at test
      A1, A2, A3, and posttest, with respect to the pretest value, amounted for
      maximally on average 17%, or 14rpm, and were larger than the corresponding
      changes in CON (p=.037). Percentage increases in minimum tangential pedal force
      in HET at test A1, A2, A3, and posttest, with respect to the pretest value, were
      larger than the corresponding changes in CON (p=.024). Heavy hip flexion strength
      training did not cause such alterations. 

PMID- 24929614
TI  - Family context assessment in a public health study.
AB  - OBJECTIVES: To analyze the factorial structure of a new instrument to assess the
      quality of the family context (Etxadi-Gangoiti Scale) in a sample from the
      Gipuzkoa cohort of the Environment and Childhood (Infancia y Medio Ambiente
      [INMA]) study. METHODS: Families in a sample of 433 two-year-old children were
      assessed in a home visit with subsequent analysis of the factorial structure and
      psychometric properties of the data. RESULTS: An exploratory factorial analysis
      (principal axis factoring and varimax rotation) and a confirmatory factorial
      analysis were carried out; partial confirmation of the original factorial
      structure of the instrument was obtained, which revealed the following factorial
      structures. Subscale (1): promotion of cognitive and linguistic development,
      social skills, psychomotor skills, and pretend play and imitation; subscale (2):
      promotion of independence and self-esteem, provision of optimal frustration,
      social and emotional quality of the relationship, and absence of physical
      punishment; subscale (3): paternal involvement, low exposure to family conflict,
      low frequency of family conflict, relationship with the extended family, social
      support, diversity of experiences, low frequency of stressful events, and low
      parental perception of stress. DISCUSSION: The structure of the original
      instrument structure was partially confirmed, which was attributed to the
      characteristics of the sample. We stress the importance of the variability
      obtained in the evaluation of the families, as well as of adequate indicators of
      reliability in such evaluation. The new instrument could be used in public health
      to identify deficient family contexts and to design preventive interventions
      focused on parenting skills.

PMID- 24929616
TI  - Scavenger receptor-recognized and enzyme-responsive nanoprobe for fluorescent
      labeling of lysosomes in live cells.
AB  - Lysosomal imaging represents a potent tool for investigating the organization of
      related cellular events and their modulation via diagnostic and therapeutic
      approaches. However, specific labeling of the lysosome in live cells is a
      significant challenge. Taking advantage of the inherent lysosomal entry of
      nanoparticles and unique digestive inclusions in the lysosome, we developed a
      nanoparticle-based, enzyme-switchable fluorescence OFF-ON strategy for specific
      labeling of the lysosome and further imaging of extracellular acidification
      induced lysosome trafficking in living cells. The nanoprobe comprised a 16 nm
      spherical gold nanoparticle as the core and an enzyme-responsive oligomer of
      fluorescein-conjugated oligo(4-vinyl-phenyl phosphate) as the shell. Due to
      quenching of the core gold nanoparticle, the nanoprobe was non-fluorescent. After
      incubation with cancer cells, the nanoprobe was rapidly internalized via
      scavenger receptor-mediated endocytosis and significantly shuffled into the
      lysosome. The nanoprobe specifically lighted up the lysosome owing to lysosome
      induced fluorescence enhancement. Specifically, digestive inclusions in the
      lysosome hydrolyzed and released gold-quenched fluorescein molecules, leading to
      significant augmentation of fluorescence. On account of specific lysosomal
      labeling, the nanoprobe effectively facilitated imaging of a 4-6 MUm anterograde
      trafficking event of the lysosome from the perinuclear region to the cell surface
      when an acidic extracellular environment developed. Our findings collectively
      highlight the use of nanoprobes for lysosomal imaging. 

PMID- 24929615
TI  - Electropolymerization of dopamine for surface modification of complex-shaped
      cardiovascular stents.
AB  - Inspired by the adhesion strategy of marine mussels, self-polymerization of
      dopamine under alkaline condition has been proven to be a simple and effective
      method for surface modification of biomaterials. However, this method still has
      many drawbacks, such as the use of alkaline aqueous medium, low poly(dopamine)
      deposition rate, and inefficient utilization of dopamine, which greatly hinder
      its practical application. In the present study, we demonstrate that
      electropolymerization of dopamine is a facile and versatile approach to surface
      tailoring of metallic cardiovascular stents, such as small and complex-shaped
      coronary stent. Electropolymerization of dopamine leads to the formation of a
      continuous and smooth electropolymerized poly(dopamine) (ePDA) coating on the
      substrate surface. This electrochemical method exhibits a higher deposition rate
      and is more efficient in dopamine utilization compared with the typical self
      polymerization method. The ePDA coating facilitates the immobilization of
      biomolecules onto substrates to engineer biomimetic microenvironments. In vitro
      and in vivo experiments demonstrate that ePDA coating functionalized with
      vascular endothelial growth factor can greatly enhance the desired cellular
      responses of endothelial cells and prevent the neointima formation after stent
      implantation. The proposed methodology may find applications in the area of
      metallic surface engineering, especially for the cardiovascular stents and
      potentially all biomedical devices with electroconductive surface as well. 

PMID- 24929619
TI  - Matrix metalloproteinase 2-responsive micelle for siRNA delivery.
AB  - Systemic delivery of small interfering RNA (siRNA) into cancer cells remains the
      major obstacle to siRNA drug development. An ideal siRNA delivery vehicle for
      systemic administration should have long circulation time in blood, accumulate at
      tumor site, and sufficiently internalize into cancer cells for high-efficiency of
      gene silence. Herein, we report a core-shell Micelleplex delivery system that
      made from block copolymer bearing poly(ethylene glycol) (PEG), matrix
      metalloproteinase 2 (MMP-2)-degradable peptide PLG*LAG, cationic cell penetrating
      peptide polyarginine r9 and poly(epsilon-caprolactone) (PCL) for siRNA delivery.
      We show clear evidences in vitro and in vivo to prove that the micelle carrying
      siRNA can circulate enough time in blood, enrich accumulation at tumor sites,
      shed the PEG layer when triggered by tumor overexpressing MMP-2, and then the
      exposing cell penetrating peptide r9 enhanced cellular uptake of siRNA.
      Accordingly, this design strategy enhances the inhibition of breast tumor growth
      following systemic injection of this system carrying siRNA against Polo-like
      kinase 1, which demonstrating this Micelleplex can be a potential delivery system
      for systemic siRNA delivery in cancer therapy. 

PMID- 24929618
TI  - Mesoporous NaYbF4@NaGdF4 core-shell up-conversion nanoparticles for targeted drug
      delivery and multimodal imaging.
AB  - We developed a facile strategy to obtain a new kind of mesoporous core-shell
      structured up-conversion nanoparticles (mUCNPs), composed of a NaYbF4:2%Er core
      and a mesoporous NaGdF4 shell. This mesoporous shell not only enhanced the up
      conversion luminescence but also endowed many other functionalities of the
      nanoparticles such as drug delivery and bio-imaging capabilities. Moreover, after
      being conjugated with polyethylenimine (PEI) and folic acid (FA), core-shell
      mUCNPs exhibited good water dispersibility, enhanced drug delivery efficiency,
      and remarkable targeting ability to cancer cells. To certify the folate receptors
      (FR)-mediated targeted drug delivery, cell viability assay, cell up-conversion
      luminescence imaging and flow cytometry analysis were carried out. Furthermore,
      apart from the application for targeted drug delivery, the as-prepared core-shell
      mUCNPs could also be employed as the contrast agents for X-ray computed
      tomography (CT) and magnetic resonance (MR) imaging, because of the strong X-ray
      attenuation ability of Yb and high longitudinal molar relaxivity (r1) of Gd in
      the nanoparticles, providing the potential for simultaneously bio-imaging and
      cancer-targeting therapy. 

PMID- 24929617
TI  - The influence of extracellular matrix composition on the differentiation of
      neuronal subtypes in tissue engineered innervated intestinal smooth muscle
      sheets.
AB  - Differentiation of enteric neural stem cells into several appropriate neural
      phenotypes is crucial while considering transplantation as a cellular therapy to
      treat enteric neuropathies. We describe the formation of tissue engineered
      innervated sheets, where intestinal smooth muscle and enteric neuronal progenitor
      cells are brought into close association in extracellular matrix (ECM) based
      microenvironments. Uniaxial alignment of constituent smooth muscle cells was
      achieved by substrate microtopography. The smooth muscle component of the tissue
      engineered sheets maintained a contractile phenotype irrespective of the ECM
      composition, and generated equivalent contractions in response to potassium
      chloride stimulation, similar to native intestinal tissue. We provided enteric
      neuronal progenitor cells with permissive ECM-based compositional and
      viscoelastic cues to generate excitatory and inhibitory neuronal subtypes. In the
      presence of the smooth muscle cells, the enteric neuronal progenitor cells
      differentiated to functionally innervate the smooth muscle. The differentiation
      of specific neuronal subtypes was influenced by the ECM microenvironment, namely
      combinations of collagen I, collagen IV, laminin and/or heparan sulfate. The
      physiology of differentiated neurons within tissue engineered sheets was
      evaluated. Sheets with composite collagen and laminin had the most similar
      patterns of Acetylcholine-induced contraction to native intestinal tissue,
      corresponding to an increased protein expression of choline acetyltransferase. An
      enriched nitrergic neuronal population, evidenced by an increased expression of
      neuronal nitric oxide synthase, was obtained in tissue engineered sheets that
      included collagen IV. These sheets had a significantly increased magnitude of
      electrical field stimulated relaxation, sensitive maximally to nitric oxide
      synthase inhibition. Tissue engineered sheets containing laminin and/or heparan
      sulfate had a balanced expression of contractile and relaxant motor neurons. Our
      studies demonstrated that neuronal subtype was modulated by varying ECM
      composition. This observation could be utilized to derive enriched populations of
      specific enteric neurons in vitro prior to transplantation. 

PMID- 24929620
TI  - Adenoviral vectors coated with cationic PEG derivatives for intravaginal
      vaccination against HIV-1.
AB  - Mucus layer coating the vaginal epithelium represents a barrier for
      intravaginally delivered recombined adenoviral (rAd) vectors, but it could be
      overcome by proper polyethylene glycol (PEG) modification. Here we synthesized
      two cationic PEG derivatives, amino-(EO)n/(AGE)m-Cyss (APCs). The polymers
      contained neutral linear PEG (2-5 kDa) to provide a hydrophilic surface and amine
      pendants to provide positive charge for coating negatively charged rAd by
      physical adsorption. Given proper molecular composition, the polymer (5k-APC)
      could coat rAd without causing aggregation, facilitating its mucus penetrating
      ability and enhancing gene expression both in vitro and in vivo. With HIVgag as
      the model antigen, the polymer-rAd complexes were administered intravaginally to
      elicit both systemic and mucosal immune responses. 5k-APC-rAd immunization
      elicited robust HIVgag-specific cellular responses and also induced higher
      antigen-specific serum IgG. More importantly, mice immunized with 5k-APC-rAd
      showed higher level of IgA in vaginal lavage fluid. These findings suggest that
      5k-APC-rAd is a promising system for intravaginal immunization against infectious
      diseases such as HIV within the vaginal tract. 

PMID- 24929621
TI  - Author's reply: To PMID 24268420.

PMID- 24929622
TI  - Theme issue 5th World Conference on Drug Absorption, Transport and Delivery.

PMID- 24929623
TI  - Comparison of racial differences in plaque composition and stenosis between HIV
      positive and HIV-negative men from the Multicenter AIDS Cohort Study.
AB  - Previous studies demonstrated that blacks have less coronary artery calcification
      (CAC) than whites. We evaluated racial differences in plaque composition and
      stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men
      underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70
      years, weighed <136 kg, and had no history of cardiac surgery or
      revascularization and, if eligible, coronary CT angiography (CTA). There were
      1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast
      CT and identified total plaque, noncalcified plaque, calcified plaque, mixed
      plaque, and coronary stenosis >50% on CTA. The association of presence and extent
      of plaque with race was determined after adjustment for HIV serostatus,
      cardiovascular risk factors, and measures of socioeconomic status. The
      prevalences of any plaque on CTA and noncalcified plaque were not different
      between black and white men; however, black men had lower prevalences of CAC
      (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002),
      and stenosis >50% (PR 0.59, p = 0.009). There were no associations between black
      race and extent of plaque in fully adjusted models. Using log-linear regression,
      black race was associated with a lower extent of any plaque on CTA in HIV
      positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p =
      0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in
      black compared with white men appears to reflect less calcification of plaque and
      stenosis rather than a lower overall prevalence of plaque. 

PMID- 24929624
TI  - Impact of sitagliptin on carotid intima-media thickness in patients with coronary
      artery disease and impaired glucose tolerance or mild diabetes mellitus.
AB  - Sitagliptin has been widely used for the treatment of diabetes and shown recently
      to have beneficial pleiotropic outcomes on cardiovascular systems in experimental
      studies. However, little is known about the influence of sitagliptin on
      atherosclerosis-related cardiovascular diseases in a clinical setting. This study
      examined the effect of sitagliptin on carotid intima-media thickness (IMT). A
      total of 76 patients with clinically stable and documented coronary artery
      disease, who were newly diagnosed with impaired glucose tolerance or mild type 2
      diabetes mellitus, were allocated, randomly, to receive either sitagliptin 100
      mg/day or the placebo control. Common carotid IMT, glucose profiles, glycosylated
      hemoglobin (HbA1c), and lipid profiles were measured at baseline and repeated at
      12 months. Sitagliptin-treated patients showed less IMT progression than the
      control group (p = 0.02). In addition, the sitagliptin group showed greater
      reductions in body weight (2.2%), 2-hour glucose levels on the 75-g oral glucose
      tolerance test (17.3%), HbA1c (4.7%), and low-density lipoprotein cholesterol
      levels (7.9%) from that at baseline. In conclusion, treatment with sitagliptin
      for 12 months was associated with a beneficial effect in the prevention of
      carotid IMT progression, compared with the diet control. 

PMID- 24929626
TI  - Decreased bone marrow stromal cells activity involves in unilateral anterior
      crossbite-induced early subchondral bone loss of temporomandibular joints.
AB  - OBJECTIVE: Subchondral bone loss in mandibular condyles was reported to be
      induced by experimentally created unilateral anterior crossbite (UAC) which
      altered the occlusal load distribution and hereafter the temporomandibular joint
      (TMJ) remodelling process. However, the initial cellular responses are poorly
      understood. In the present study, changes in osteoblast and osteoclast activities
      in TMJ subchondral bone were investigated using the rats treated with UAC.
      DESIGN: Forty rats were randomly divided into UAC and control groups, and sampled
      at 2 weeks after the operation. Subchondral bone loss was evaluated by micro-CT.
      Osteoclast and osteoblast activities were analyzed by real-time PCR. The
      osteoblast differentiation of the locally isolated BMSCs from TMJ subchondral
      bone was assessed by Alizarin red staining. The migration of BMSCs was detected
      by transwell assays. RESULTS: Compared with the age-matched controls, TMJ
      subchondral bone loss was observed in the UAC-treated rats (p<0.05). The
      osteoblast activity evaluated by real-time PCR and osteoblast number revealed by
      immunohistochemical staining were reduced in the TMJ subchondral bone of UAC rats
      (p<0.05), and the capability of proliferation, migration and osteoblast
      differentiation were all decreased in the locally isolated BMSCs from the UAC
      group (p<0.05). CONCLUSIONS: The present data demonstrated an involvement of
      reduced BMSCs activity in the initiation of the mandibular subchondral bone loss
      at the early stage of installation of the aberrant prostheses.

PMID- 24929625
TI  - Usefulness of electrocardiographic QRS/T angles with versus without bundle branch
      blocks to predict heart failure (from the Atherosclerosis Risk in Communities
      Study).
AB  - Repolarization abnormalities in the setting of bundle branch blocks (BBB) are
      generally ignored. We used Cox regression models to determine hazard ratios (HRs)
      with 95% confidence intervals (CIs) for incident heart failure (HF) associated
      with wide spatial and frontal QRS/T angle (upper twenty-fifth percentile of each)
      in men and women with and without BBB. This analysis included 14,478 participants
      (54.6% women, 26.4% blacks, 377 [2.6%] with BBB) from the Atherosclerosis Risk in
      Communities Study who were free of HF at baseline. Using No-BBB with normal
      spatial QRS/T angle as the reference group, the risk for HF in multivariable
      adjusted models was increased 51% for No-BBB with wide spatial QRS/T angle (HR
      1.51, 95% CI 1.37 to 1.66), 48% for BBB with normal spatial QRS/T angle (HR 1.48,
      95% CI 1.17 to 1.88), and the risk for incident HF was increased more than
      threefold for BBB with wide spatial QRS/T angle (HR 3.37, 95% CI 2.47 to 4.60).
      The results were consistent across subgroups by gender. Similar results were
      observed for the frontal plane QRS/T angle. In the pooled BBB group excluding
      right BBB, a positive T wave in lead aVR and heart rate 70 bpm and higher were
      also potent predictors of incident HF similar to the QRS/T angles. In conclusion,
      both BBB and wide QRS/T angles are predictive of HF, and concomitant presence of
      both carries a much higher risk than for either predictor alone. These findings
      suggest that repolarization abnormalities in the setting of BBB should not be
      considered benign or an expected consequence of BBB. 

PMID- 24929627
TI  - [Not Available].

PMID- 24929629
TI  - Applying the min-projection strategy to improve the transient performance of the
      three-phase grid-connected inverter.
AB  - Applying the min-projection strategy (MPS) to a three-phase grid-connected
      inverter to improve its transient performance is the main objective of this
      paper. For this purpose, the inverter is first modeled as a switched linear
      system. Then, the feasibility of the MPS technique is investigated and the
      stability criterion is derived. Hereafter, the fundamental equations of the MPS
      for the control of the inverter are obtained. The proposed scheme is simulated in
      PSCAD/EMTDC environment. The validity of the MPS approach is confirmed by
      comparing the obtained results with those of VOC method. The results demonstrate
      that the proposed method despite its simplicity provides an excellent transient
      performance, fully decoupled control of active and reactive powers, acceptable
      THD level and a reasonable switching frequency. 

PMID- 24929630
TI  - Hinfinity mode-dependent fault detection filter design for stochastic Markovian
      jump systems with time-varying delays and parameter uncertainties.
AB  - This paper deals with the problem of robust Hinfinity fault detection for a class
      of stochastic Markovian jump systems (SMJSs) The aim is to design a linear mode
      dependent fault detection filter such that the fault detection system is not only
      stochastically asymptotically stable in the large, but also satisfies a
      prescribed Hinfinity-norm level for all admissible uncertainties. By using
      Lyapunov stability theory and generalized Ito formula, some novel mode-dependent
      and delay-dependent sufficient conditions in terms of linear matrix inequality
      (LMI) are proposed to insure the existence of the desired fault detection filter.
      A simulation example and an industrial nonisothermal continuous stirred tank
      reactor (CSTR) system are employed to show the effectiveness of the proposed
      method. 

PMID- 24929631
TI  - Risks and prevention of severe RS virus infection among children with
      immunodeficiency and Down's syndrome.
AB  - By the age of two years, almost all infants are infected with the Respiratory
      syncytial virus (RSV). One of the main causes of hospitalizations for
      bronchiolitis and pneumonia at this age is RSV infection. In addition to well
      known risks for severe RSV disease, such as prematurity, bronchopulmonary
      dysplasia and congenital heart disease, immunodeficiencies, chromosomal
      abnormalities such as Down's syndrome or neuromuscular diseases have also been
      identified as risks. While the medical needs for RSV prevention in these risk
      groups are high, clinical evidence to support this is limited. Palivizumab was
      recently approved in Japan for prophylaxis in children with immunodeficiency or
      Down's syndrome. A clinical guidance protocol for the prevention of RSV infection
      using Palivizumab in these risk groups is provided here on the basis of a review
      of the available literature and on expert opinion. Thus, the present article
      reviews the published literature related to RSV infections in infants and
      children with immunodeficiencies or Down's syndrome in order to outline the
      risks, pathology and physiology of severe RSV disease in these patient groups.
      The purpose of this article is to facilitate understanding of the medical
      scientific bases for the clinical guidance. 

PMID- 24929628
TI  - Eri1: a conserved enzyme at the crossroads of multiple RNA-processing pathways.
AB  - Eri1 is an evolutionarily conserved 3'-5' exoribonuclease that participates in
      5.8S rRNA 3' end processing and turnover of replication-dependent histone mRNAs.
      Over the course of evolution, Eri1 has also been recruited into a variety of
      conserved and species-specific regulatory small RNA pathways that include
      endogenous small interfering (si)RNAs and miRNAs. Recent advances in Eri1 biology
      illustrate the importance of RNA metabolism in epigenetic gene regulation and
      illuminate common principles and players in RNA biogenesis and turnover. In this
      review, we highlight Eri1 as a member of a growing class of ribosome- and histone
      mRNA-associated proteins that have been recruited into divergent RNA metabolic
      pathways. We summarize recent advances in the understanding of Eri1 function in
      these pathways and discuss how Eri1 impacts gene expression and physiology in a
      variety of eukaryotic species. This emerging view highlights the possibility for
      crosstalk and coregulation of diverse cellular processes regulated by RNA. 

PMID- 24929632
TI  - A comparison of two methods of foot health education: the Fremantle Diabetes
      Study Phase II.
AB  - AIMS: To compare the effectiveness of two different methods of education on foot
      health, behaviours and attitudes in patients with type 2 diabetes. METHODS:
      Community-based patients were consecutively allocated to written education (Group
      A) or an interactive educator-led session (Group B). A quantitative Foot Score
      (maximum 90 points score based on severity of treatable pathology), the
      Nottingham Assessment of Functional Foot Care (NAFFC) survey score (maximum 30
      points reflecting frequency of foot care behaviours) and a 6-question survey of
      attitudes to foot complications were administered at baseline and 3 months.
      RESULTS: 154 patients (mean+/-SD age 68+/-10 years, 59.7% males, median
      [interquartile range] diabetes duration 11.5 [5.6-18.9] years) were recruited.
      There was a greater change (Delta) in Foot Score from baseline to 3 months in
      Group A (8.3+/-3.6, Delta-1.8 (95% CI: -2.4 to -1.2) vs Group B (6.8+/-2.6, Delta
      0.1 (-0.7 to 0.4); P<0.001), but no change in NAFFC survey score in either group
      (P=0.13). In the attitudes survey, Group B felt they better understood how to
      prevent foot complications than Group A after education (P=0.031). CONCLUSIONS:
      Written information was more effective at improving foot health while interactive
      education improved confidence in undertaking preventive measures, suggesting that
      the most effective foot care education should include both components.

PMID- 24929633
TI  - Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in
      hospitalized patients.
AB  - INTRODUCTION: Prescribing medication is an important aspect of almost all in
      hospital treatment regimes. Besides their obviously beneficial effects, medicines
      can also cause adverse drug events (ADE), which increase morbidity, mortality and
      health care costs. Partially, these ADEs arise from medication errors, e.g. at
      the prescribing stage. ADEs caused by medication errors are preventable ADEs.
      Until now, medication ordering was primarily a paper-based process and
      consequently, it was error prone. Computerized Physician Order Entry, combined
      with basic Clinical Decision Support System (CPOE/CDSS) is considered to enhance
      patient safety. Limited information is available on the balance between the
      health gains and the costs that need to be invested in order to achieve these
      positive effects. Aim of this study was to study the balance between the effects
      and costs of CPOE/CDSS compared to the traditional paper-based medication
      ordering. METHODS: The economic evaluation was performed alongside a clinical
      study (interrupted time series design) on the effectiveness of CPOE/CDSS,
      including a cost minimization and a cost-effectiveness analysis. Data collection
      took place between 2005 and 2008. Analyses were performed from a hospital
      perspective. The study was performed in a general teaching hospital and a
      University Medical Centre on general internal medicine, gastroenterology and
      geriatric wards. Computerized Physician Order Entry, combined with basic Clinical
      Decision Support System (CPOE/CDSS) was compared to a traditional paper based
      system. All costs of both medication ordering systems are based on resources used
      and time invested. Prices were expressed in Euros (price level 2009).
      Effectiveness outcomes were medication errors and preventable adverse drug
      events. RESULTS: During the paper-based prescribing period 592 patients were
      included, and during the CPOE/CDSS period 603. Total costs of the paper-based
      system and CPOE/CDSS amounted to ?12.37 and ?14.91 per patient/day respectively.
      The Incremental Cost-Effectiveness Ratio (ICER) for medication errors was 3.54
      and for preventable adverse drug events 322.70, indicating the extra amount (?)
      that has to be invested in order to prevent one medication error or one pADE.
      CONCLUSIONS: CPOE with basic CDSS contributes to a decreased risk of preventable
      harm. Overall, the extra costs of CPOE/CDSS needed to prevent one ME or one pADE
      seem to be acceptable.

PMID- 24929634
TI  - Prevalence of ultrasound-detected residual synovitis and risk of relapse and
      structural progression in rheumatoid arthritis patients in clinical remission: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The aims of this study were to assess the prevalence of US-detected
      residual synovitis in patients with RA in clinical remission (CR) and evaluate
      its predictive value for relapse and structural progression. METHODS: We
      performed a systematic literature search of Medline, Embase and rheumatology
      meeting databases from 1 January 2001 to 28 May 2012. The prevalence of US grey
      scale (USGS) signals (synovial hypertrophy or joint effusion) and power Doppler
      (PD) signals were collected, taking into account CR definitions [44-joint DAS
      (DAS44), 28-joint DAS (DAS28), SDAI, ACR 1981 or ACR/European League Against
      Rheumatism 2011], stage of RA (early or long-standing) and US examination (from 5
      to 44 joints assessed). A meta-analysis assessing the risk of relapse or
      structural progression in patients with synovitis involved the Mantel-Haenszel
      method. RESULTS: We included 19 studies of 1618 patients, 1369 in remission. The
      prevalence of USGS positive (USGS+), USGS+/PD negative (PD-), USGS+/PD positive
      (PD+) and USGS negative (USGS-/PD- was 84%, 41%, 44% and 15%, respectively. The
      prevalence of USGS+ or USGS+/PD+ was comparable among CR definitions and US
      methods. The prevalence of USGS+ and USGS+/PD+ was greater for long-standing than
      early RA (P < 0.001). Meta-analyses of five studies (271 patients), three studies
      (173 patients) and two studies (798 joints) revealed an association of USGS+/PD+
      and risk of relapse [odds ratio (OR) 3.2 (95% CI 1.8, 5.9), P = 0.0001, I(2) =
      0%] and structural progression in individual patients [OR 9.13 (95% CI 1.1,
      74.3), P = 0.04, I(2) = 43%] and joints [OR 6.95 (95% CI 3.4, 13.9), P < 0.0001,
      I(2) = 6%] over 1-2 years. CONCLUSION: US-detected residual synovitis is frequent
      and predicts the risk of relapse and structural progression in RA patients with
      CR.

PMID- 24929635
TI  - Neural correlates of fatigue in granulomatosis with polyangiitis: a functional
      magnetic resonance imaging study.
AB  - OBJECTIVE: The aim of this study was to investigate the neurophysiological
      effects of fatigue among patients with granulomatosis with polyangiitis (GPA).
      METHODS: A case-control functional MRI (fMRI) study was conducted. Stable GPA
      subjects were recruited according to fatigue status, with those reporting fatigue
      defined as cases and those not defined as controls. In addition, a control group
      of general population subjects with idiopathic fatigue were studied. During fMRI,
      all participants performed a fatigue-inducing cognitive task. Functional data
      were acquired with a 3 T MRI scanner during periods of task activity and rest.
      Analyses of the differences in blood oxygen level dependent (BOLD) signal were
      then performed using SPM8 software and comparisons were made between case and
      control groups. RESULTS: GPA cases (n = 12) were demographically matched to GPA
      controls (n = 14) and were clinically similar apart from the higher reporting of
      fatigue, by design, and depressive symptoms (P = 0.0007). After adjusting for
      depressive symptoms, comparison of BOLD signals revealed significantly greater
      activation in the right thalamus, left paracentral lobule, left medial frontal
      gyrus and right medial globus pallidus among GPA cases. When compared with the
      similarly fatigued population control group (n = 13), GPA cases shared many
      overlapping areas of activation. However, in addition, the population control
      group revealed significantly greater activation elsewhere, principally the left
      precentral gyrus, right superior frontal gyrus and right cingulate gyrus.
      CONCLUSION: fMRI has identified specific differences in the neurophysiology of
      fatigued GPA subjects. Future application of this promising biomarker may inform
      the precise mechanisms of this clinically important symptom.

PMID- 24929636
TI  - Changes in the adsorption of bisphenol A, 17 alpha-ethinyl estradiol, and
      phenanthrene on marine sediment in Hong Kong in relation to the simulated
      sediment organic matter decomposition.
AB  - Marine sediment with an input of particulate organic matter was incubated to
      simulate the early aging process. On the sediment after various incubation
      periods, adsorption and desorption tests were conducted for three selected
      organic micropollutants: bisphenol A (BPA), 17alpha-ethinyl estradiol (EE2), and
      phenanthrene (Phe). The results showed significant sediment organic matter (SOM)
      decomposition during the incubation, and the SOM decay and transformation had a
      profound impact on the adsorption of organic compounds by the sediment. An
      increasing-delay-increasing pattern of change was observed for the SOM normalized
      partition coefficients of EE2 and Phe. This change was accordant to the
      transformation of SOM from labile organics into active biomass and its microbial
      products, and finally into more condensed and humic-like substances. Comparison
      between the 3 model micropollutants indicates that the chemical adsorption
      behaviors were mostly affected by their hydrophobic properties. 

PMID- 24929637
TI  - Genome-wide methylomic analysis of monozygotic twins discordant for adolescent
      depression.
AB  - BACKGROUND: Adolescent depression is a common neuropsychiatric disorder that
      often continues into adulthood and is associated with a wide range of poor
      outcomes including suicide. Although numerous studies have looked at genetic
      markers associated with depression, the role of epigenetic variation remains
      relatively unexplored. METHODS: Monozygotic (MZ) twins were selected from an
      adolescent twin study designed to investigate the interplay of genetic and
      environmental factors in the development of emotional and behavioral
      difficulties. There were 18 pairs of MZ twins identified in which one member
      scored consistently higher (group mean within the clinically significant range)
      on self-rated depression than the other. We assessed genome-wide patterns of DNA
      methylation in twin buccal cell DNA using the Infinium HumanMethylation450
      BeadChip from Illumina. Quality control and data preprocessing was undertaken
      using the wateRmelon package. Differentially methylated probes (DMPs) were
      identified using an analysis strategy taking into account both the significance
      and the magnitude of DNA methylation differences. The top differentially
      methylated DMP was successfully validated by bisulfite-pyrosequencing, and
      identified DMPs were tested in postmortem brain samples obtained from patients
      with major depressive disorder (n = 14) and matched control subjects (n = 15).
      RESULTS: Two reproducible depression-associated DMPs were identified, including
      the top-ranked DMP that was located within STK32C, which encodes a
      serine/threonine kinase, of unknown function. CONCLUSIONS: Our data indicate that
      DNA methylation differences are apparent in MZ twins discordant for adolescent
      depression and that some of the disease-associated variation observed in buccal
      cell DNA is mirrored in adult brain tissue obtained from individuals with
      clinical depression.

PMID- 24929638
TI  - Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular
      carcinoma: a large retrospective multicenter cohort study.
AB  - BACKGROUND: The number of hepatocellular carcinoma (HCC) patients with non-viral
      etiologies is increasing in Japan. We conducted a nation-wide survey to examine
      the characteristics of those patients. METHODS: After we assessed the trend of
      patients who were first diagnosed with HCC at 53 tertiary care centers in Japan
      from 1991 to 2010, we collected detailed data of 5326 patients with non-viral
      etiology. The etiologies were categorized as autoimmune hepatitis, primary
      biliary cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver
      disease (NAFLD), unclassified, and other. Baseline characteristics at initial
      diagnosis, the modality of the initial treatment, and survival status were
      collected via a website. Survival of the patients was assessed by the Kaplan
      Meier method and Cox proportional hazard regression. RESULTS: The proportion of
      patients with non-viral etiologies increased from 10.0% in 1991 to 24.1% in 2010.
      Of the patients, 92% were categorized as ALD, NAFLD, or unclassified. Body mass
      index (BMI) was >= 25 kg/m(2) in 39%. Diabetes was most prevalent in NAFLD (63%),
      followed by unclassified etiology (46%) and ALD (45%). Approximately 80% of
      patients underwent radical therapy, including resection, ablation, or
      transarterial chemoembolization. Survival rates at 3, 5, 10, 15, and 20 years
      were 58.2, 42.6, 21.5, 15.2, and 15.2%, respectively. Multivariate analysis
      revealed that patients with BMI > 22 and <= 25 kg/m(2) showed the best prognosis
      versus other BMI categories, after adjusting by age, gender, tumor-related
      factors, and Child-Pugh score. CONCLUSIONS: Most cases of non-B, non-C HCC are
      related to lifestyle factors, including obesity and diabetes. Slightly overweight
      patients showed the best prognosis.

PMID- 24929639
TI  - An evaluation of sampling methods used to produce insect growth models for
      postmortem interval estimation.
AB  - Many authors produced carrion insect development data for predicting the age of
      an insect from a corpse. Under some circumstances, this age value is a minimum
      postmortem interval. There are no standard protocols for such experiments, and
      the literature includes a variety of sampling methods. To our knowledge, there
      has been no investigation of how the choice of sampling method can be expected to
      influence the performance of the resulting predictive model. We calculated 95 %
      inverse prediction confidence limits for growth curves of the forensically
      important carrion flies Chrysomya megacephala and Sarconesia chlorogaster
      (Calliphoridae) at a constant temperature. Confidence limits constructed on data
      for entire age cohorts were considered to be the most realistic and were used to
      judge the effect of various subsampling schemes from the literature. Random
      subsamples yielded predictive models very similar to those of the complete data.
      Because taking genuinely random subsamples would require a great deal of effort,
      we imagine that it would be worthwhile only if the larval measurement technique
      were especially slow and/or expensive. However, although some authors claimed to
      use random samples, their published methods suggest otherwise. Subsampling the
      largest larvae produced a predictive model that performed poorly, with confidence
      intervals about an estimate of age being unjustifiably narrow and unlikely to
      contain the true age. We believe these results indicate that most forensic insect
      development studies should involve the measurement of entire age cohorts rather
      than subsamples of one or more cohorts. 

PMID- 24929640
TI  - Analysis of linkage and linkage disequilibrium for syntenic STRs on 12
      chromosomes.
AB  - The purpose of this study is to evaluate allelic association and linkage of 18
      adjacent syntenic short tandem repeat (STR) pairs form out of 30 markers located
      on 12 different autosomes. Linkage disequilibrium was tested by using the unknown
      gametic phase genotypes and phased haplotypes from 290 unrelated individuals from
      Chinese Han population. Genetic linkage analysis between syntenic STRs was
      performed based on 145 two-generation families which involved 628 meioses. The
      results showed no significant linkage disequilibrium at any STR pairs and
      independent inheritance between syntenic STR pairs was indicated. Significant
      linkage (maximum logarithm of odd (LOD) scores >3.0) was found in 6 out of the 18
      adjacent syntenic STR pairs (D1S1627-D1S1677, CSF1PO-D5S818, D6S1017-D6S1043,
      D6S1043-D6S474, D12S391-vWA, and D19S253-D19S433). These significant linkage
      marker pairs had a genetic distance ranged from 11.94 to 41.33 cM deduced from
      HapMap. When recombination fractions determined in families were compared to
      those derived from Kosambi mapping function based on HapMap data, the latter may
      have an overestimation. In summary, our results demonstrated that product rule
      included syntenic STRs can be used for unrelated individual profile probability
      and the recombination fraction based on family data was superior to the
      estimation from HapMap for kinship analysis.

PMID- 24929641
TI  - Electromagnetic tracking for catheter reconstruction in ultrasound-guided high
      dose-rate brachytherapy of the prostate.
AB  - PURPOSE: The accurate delivery of high-dose-rate brachytherapy is dependent on
      the correct identification of the position and shape of the treatment catheters.
      In many brachytherapy clinics, transrectal ultrasound (TRUS) imaging is used to
      identify the catheters. However, manual catheter identification on TRUS images
      can be time consuming, subjective, and operator dependent because of
      calcifications and distal shadowing artifacts. We report the use of
      electromagnetic (EM) tracking technology to map the position and shape of
      catheters inserted in a tissue-mimicking phantom. METHODS AND MATERIALS: The
      accuracy of the EM system was comprehensively quantified using a three-axis
      robotic system. In addition, EM tracks acquired from catheters in a phantom were
      compared with catheter positions determined from TRUS and CT images to compare EM
      system performance to standard clinical imaging modalities. The tracking
      experiments were performed in a controlled laboratory environment and also in a
      typical brachytherapy operating room to test for potential EM distortions.
      RESULTS: The robotic validation of the EM system yielded a mean accuracy of <0.5
      mm for a clinically acceptable field of view in a nondistorting environment. The
      EM-tracked catheter representations were found to have an accuracy of <1 mm when
      compared with TRUS- and CT-identified positions, both in the laboratory
      environment and in the brachytherapy operating room. The achievable accuracy
      depends to a large extent on the calibration of the TRUS probe, geometry of the
      tracked devices relative to the EM field generator, and locations of surrounding
      clinical equipment. To address the issue of variable accuracy, a robust
      calibration algorithm has been developed and integrated into the workflow. The
      proposed mapping technique was also found to improve the workflow efficiency of
      catheter identification. CONCLUSIONS: The high baseline accuracy of the EM
      system, the consistent agreement between EM-tracked, TRUS- and CT-identified
      catheters, and the improved workflow efficiency illustrate the potential value of
      using EM tracking for catheter mapping in high-dose-rate brachytherapy.

PMID- 24929642
TI  - Volume of high-dose regions and likelihood of locoregional control after
      perioperative high-dose-rate brachytherapy: do hotter implants work better?
AB  - PURPOSE: To determine whether perioperative high-dose-rate brachytherapy (PHDRB)
      implants with larger high-dose regions produce increased locoregional control.
      METHODS AND MATERIALS: Patients (n=166) enrolled in several PHDRB prospective
      studies conducted at the University of Navarre were analyzed. The PHDRB was given
      to total doses of 16Gy/4 b.i.d. or 24Gy/6 b.i.d. treatments for negative or
      close/positive margins along with 45Gy/25 Rx of external beam radiation therapy.
      The histogram-based generalized equivalent uniform dose (EUD) formulism was used
      to quantify and standardize the dose-volume histogram into 2-Gy equivalents. The
      region of interest analyzed included: tissue volume encompassed by the
      prescription isodose of 4Gy (TV100). Routine dose reporting parameters such as
      physical dose and single-point 2-Gy equivalent dose were used for reference.
      RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have
      failed, and 116 remain controlled at last followup. Overall, EUD was not
      different in the patients who failed compared with controls (89.1Gy vs. 86.5Gy;
      p=not significant). When patients were stratified by risk using the University of
      Navarre Predictive Model, very high-risk patients (i.e., tumors >=3cm resected
      with close <1mm/positive margins) had an improved locoregional control with
      higher EUD values (p=0.028). This effect was not observed in low-, intermediate-,
      and high-risk University of Navarre Predictive Model categories. CONCLUSIONS: In
      very high-risk patients, enlarged high-dose regions can produce a dose-response
      effect. Routine dose reporting methods such as physical dose and single-point 2
      Gy equivalent dose may not show this effect, but it can be revealed by histogram
      based EUD assessment.

PMID- 24929643
TI  - Common trend: move to enucleation-Is there a case for GreenLight enucleation?
      Development and description of the technique.
AB  - BACKGROUND: Transurethral laser prostatectomy has evolved as a viable alternative
      for the management of benign prostate enlargement. Since the renaissance of laser
      prostatectomy with the advent of the holmium:yttrium-aluminum-garnet laser in the
      1990s, various lasers and subsequent procedures have been introduced. These
      techniques can be categorized as vaporizing, resecting, and enucleating
      approaches. Photoselective vaporization of the prostate (PVP) is dominated by
      high-power lithium triborate (LBO) crystal lasers (GreenLight XPS). The mainstay
      of this technique is for the treatment of small to medium prostate volumes
      whereas enucleating techniques, such as holmium laser enucleation of the prostate
      and thulium enucleation of the prostate, focus on large-volume glands. In order
      to perspectively "delimit" LBO into the field of large-volume prostates, we
      developed LBO en bloc enucleation to render it as a competing transurethral
      enucleating approach. MATERIALS AND METHODS: We present a detailed stepwise
      progressive technique developed in Madrid, Spain, for the complete removal of the
      transitional zone by vapoenucleation. The steps include exposition of the
      prostatic capsule by PVP toward the peripheral zone, thereby identifying the
      anatomical limits of enucleation. Subsequently, the transitional zone is excised
      in a single bloc and morcellated after its placement into the bladder.
      CONCLUSION: This new GreenLight en bloc enucleation technique allows to treat
      larger prostates than those previously treated with the PVP technique.

PMID- 24929644
TI  - Methylation-capture and Next-Generation Sequencing of free circulating DNA from
      human plasma.
AB  - BACKGROUND: Free circulating DNA (fcDNA) has many potential clinical
      applications, due to the non-invasive way in which it is collected. However,
      because of the low concentration of fcDNA in blood, genome-wide analysis carries
      many technical challenges that must be overcome before fcDNA studies can reach
      their full potential. There are currently no definitive standards for fcDNA
      collection, processing and whole-genome sequencing. We report novel detailed
      methodology for the capture of high-quality methylated fcDNA, library preparation
      and downstream genome-wide Next-Generation Sequencing. We also describe the
      effects of sample storage, processing and scaling on fcDNA recovery and quality.
      RESULTS: Use of serum versus plasma, and storage of blood prior to separation
      resulted in genomic DNA contamination, likely due to leukocyte lysis. Methylated
      fcDNA fragments were isolated from 5 donors using a methyl-binding protein-based
      protocol and appear as a discrete band of ~180 bases. This discrete band allows
      minimal sample loss at the size restriction step in library preparation for Next
      Generation Sequencing, allowing for high-quality sequencing from minimal amounts
      of fcDNA. Following sequencing, we obtained 37 * 10(6)-86 * 10(6) unique mappable
      reads, representing more than 50% of total mappable reads. The methylation status
      of 9 genomic regions as determined by DNA capture and sequencing was
      independently validated by clonal bisulphite sequencing. CONCLUSIONS: Our
      optimized methods provide high-quality methylated fcDNA suitable for whole-genome
      sequencing, and allow good library complexity and accurate sequencing, despite
      using less than half of the recommended minimum input DNA.

PMID- 24929645
TI  - Adolescent age and heart transplantation outcomes in myocarditis or congenital
      heart disease.
AB  - BACKGROUND: Adolescents often fare poorly after heart transplantation. However,
      whether the effect of age varies according to the etiology of heart failure is
      unknown. We tested the hypothesis that age-related heart transplantation outcomes
      are different in patients with myocarditis and congenital heart disease (CHD).
      METHODS: A retrospective analysis of the United Network of Organ Sharing database
      was performed for patients with myocarditis (n = 709) and CHD (n = 1,631)
      undergoing heart transplantation from 1987 to 2011. The effect of age on graft
      survival was assessed. Age was categorized as children (6-12 years), adolescents
      (13-18 years), younger adults (19-30 years), and older adults (31-50 years).
      RESULTS: For myocarditis, the median graft survival for adolescents was 6.9 years
      (95% confidence interval [CI], 5.6-9.6), which was significantly lower than other
      age groups (children: 14.1 [95% CI, 9.8-10.9] years, p = 0.004; younger adults:
      11.8 [95% CI, 8.3-15.2] years, p = 0.172; older adults: 12.0 years [95% CI, 10.0
      14.3 years], p = 0.033). For CHD, the median graft survival for adolescents was
      7.4 years (95% CI, 6.8-8.6), which was not significantly different from other age
      groups (children: 9.0 [95% CI, 7.9-11.0] years, p = 0.737; younger adults: 11.2
      [95% CI, 8.6-13.3] years, p = 0.744; older adults: 11.6 [95% CI, 9.2-15.3] years,
      p = 0.608). Multivariable analysis showed adolescent age was independently
      associated with worse graft survival for patients with myocarditis but not for
      CHD. CONCLUSIONS: Adolescents with myocarditis have significantly worse graft
      survival after heart transplantation, but adolescents with CHD have similar
      outcomes to other patients with CHD. Further study is needed to improve outcomes
      in this vulnerable population.

PMID- 24929646
TI  - Advanced heart failure in patients infected with human immunodeficiency virus: is
      there equal access to care?
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection has evolved from a
      highly stigmatized disease with certain progression to acquired immunodeficiency
      syndrome (AIDS) to a chronic disease affecting over 1 million Americans. With the
      success of current anti-retroviral therapies, cardiovascular disease, including
      advanced heart failure (HF), will be a major cause of morbidity and mortality in
      this population. METHODS: A survey concerning heart transplantation (HT) and left
      ventricular assist device (LVAD) implantation attitudes and outcomes in HIV
      infected patients was distributed to 103 American and 9 Canadian HT centers via
      fax, e-mail or telephone. RESULTS: Eighty-nine centers (79%) responded. Eighteen
      HTs were performed in HIV(+) patients with 1-, 2- and 5-year survival of 100%,
      100% and 63%, respectively. Eighty-two centers (92%) have never performed HT in
      HIV(+) patients and 51 centers (57%) marked HIV(+) status as a contraindication.
      Rationales for contraindication included: (1) high-risk patients should be
      avoided given the scarcity of organ supply (59%); (2) immunosuppression required
      for HT may induce progression to AIDS (51%); and (3) drug interactions may worsen
      patients' clinical outcomes (49%). Thirty-five left ventricular assist device
      (LVAD) implantations in HIV(+) patients were reported. Sixty-eight centers (76%)
      have never implanted an LVAD in an HIV(+) patient and 21 centers (20%) marked
      HIV(+) status as a contraindication, of which 61% indicated concern for device
      related infection. CONCLUSIONS: Most centers either explicitly consider HIV(+)
      status as a contraindication for or have never treated HIV(+) patients with
      advanced HF therapy. Our findings suggest unequal access to care and underscore
      the need to educate cardiovascular health-care providers on progress made with
      HIV therapies.

PMID- 24929647
TI  - Do reviews of healthcare interventions teach us how to improve healthcare
      systems?
AB  - Planners, managers and policy makers in modern health services are not without
      ingenuity - they will always try, try and try again. They face deep-seated or
      'wicked' problems, which have complex roots in the labyrinthine structures though
      which healthcare is delivered. Accordingly, the interventions devised to deal
      with such stubborn problems usually come in the plural. Many different reforms
      are devised to deal with a particular stumbling block, which may be implemented
      sequentially, simultaneously or whenever policy fashion or funding dictates. This
      paper examines this predicament from the perspective of evidence based policy.
      How might researchers go about reviewing the evidence when they are faced with
      multiple or indeed competing interventions addressing the same problem? In the
      face of this plight a rather unheralded form of research synthesis has emerged,
      namely the 'typological review'. We critically review the fortunes of this
      strategy. Separating the putative reforms into series of subtypes and producing a
      scorecard of their outcomes has the unintended effect of divorcing them all from
      an understanding of how organisations change. A more fruitful approach may lie in
      a 'theory-driven review' underpinned by an understanding of dynamics of social
      change in complex organisations. We test this thesis by examining the primary and
      secondary research on the many interventions designed to tackle a particularly
      wicked problem, namely the inexorable rise in demand for healthcare. 

PMID- 24929648
TI  - The effect of image guidance on dose distributions in breast boost radiotherapy.
AB  - AIMS: To determine the effect of image-guided radiotherapy on the dose
      distributions in breast boost treatments. MATERIALS AND METHODS: Computed
      tomography images from a cohort of 60 patients treated within the IMPORT HIGH
      trial (CRUK/06/003) were used to create sequential and concomitant boost
      treatment plans (30 cases each). Two treatment plans were created for each case
      using tumour bed planning target volume (PTV) margins of 5 mm (achieved with
      image-guided radiotherapy) and 8 mm (required for bony anatomy verification).
      Dose data were collected for breast, lung and heart; differences with margin size
      were tested for statistical significance. RESULTS: A median decrease of 29 cm(3)
      (range 11-193 cm(3)) of breast tissue receiving 95% of the prescribed dose was
      observed where image-guided radiotherapy margins were used. Decreases in doses to
      lungs, contralateral breast and heart were modest, but statistically significant
      (P < 0.01). Plan quality was compromised with the 8 mm PTV margin in one in eight
      sequential boost plans and one third of concomitant boost plans. Tumour bed PTV
      coverage was <95% (>91%) of the prescribed dose in 12 cases; in addition, the
      required partial breast median dose was exceeded in nine concomitant boost cases
      by 0.5-3.7 Gy. CONCLUSIONS: The use of image guidance and, hence, a reduced
      tumour bed PTV margin, in breast boost radiotherapy resulted in a modest
      reduction in radiation dose to breast, lung and heart tissues. Reduced margins
      enabled by image guidance were necessary to discriminate between dose levels to
      multiple PTVs in the concomitant breast boost plans investigated.

PMID- 24929649
TI  - R-CHOP versus R-COMP: are they really equally effective?
AB  - The first-line standard treatment for diffuse large B-cell lymphoma (DLBCL) is
      the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine,
      prednisone). It is associated with cardiotoxicity, which is why new treatment
      strategies are needed. Liposomial doxorubicin has been proven to reduce these
      side-effects, but until now a direct comparison regarding efficacy has not yet
      been published. We retrospectively assessed 364 consecutive DLBCL patients who
      underwent either R-CHOP (218; 60%) or R-COMP (doxorubicin replaced by non
      pegylated liposomal doxorubicin; 146; 40%) in first line and compared outcome and
      survival. We provide evidence that both regimens induce a high and comparable
      number of complete remissions and that both are able to cure patients with DLBCL.
      Confirmatory data are needed. 

PMID- 24929650
TI  - Epilepsy and its main psychiatric comorbidities in adults and children.
AB  - Psychiatric disorders seem to be more frequent in patients with epilepsy (PWE)
      than the general population. Although researchers have documented a strong
      association between epilepsy and psychiatric comorbidities, the nature of this
      relationship is poorly understood. According to this, psychiatric diseases are
      often underdiagnosed and undertreated in PWE with further decrease of the quality
      of life of patients. The aim of the review was to examine the most frequent
      psychiatric comorbidities in adults with epilepsy (AWE) and the main psychiatric
      comorbidities in children with epilepsy (CWE) in order to better understand the
      relationship between epilepsy and the development of psychiatric disorders. 

PMID- 24929651
TI  - Clinical and serological study of myasthenia gravis using both
      radioimmunoprecipitation and cell-based assays in a South Asian population.
AB  - BACKGROUND: Identification of autoantibodies has defined distinct clinico-immuno
      pathological subtypes of myasthenia gravis (MG) such as AChR-antibody-positive-MG
      and MuSK-antibody-positive-MG. The use of more sensitive assays such as the cell
      based assay (CBA) is expected to reduce the proportion of seronegative-MG. We
      studied the seroprevalence of AChR and MuSK antibodies using both
      radioimmunoprecipitation (RIA) and CBA amongst MG patients in Sri Lanka and
      related their antibody status to their clinical subtypes and severity. METHODS:
      113 patients with MG attending Neurology units in the district of Colombo were
      studied. Clinical data were obtained using an interviewer-administered
      questionnaire and medical records. The severity of MG was assessed according to
      MGFA clinical grading. RIA and CBA were used to detect serum AChR and MuSK
      antibodies. Patients with other neurological diseases were recruited as controls.
      RESULTS: We detected either AChRAb (85%) or MuSKAb (6.2%) in 91.2% of MG
      patients. Complementing the RIA with the CBA improved the diagnostic power of
      detecting AChRAbs by 21% and MuSKAbs by 77%. The clinical characteristics and the
      occurrence of thymic pathology were similar to other populations except for a
      male preponderance (1.5:1). The AChRAb titer appeared to parallel the clinical
      severity. Seven of 11 (63.6%) patients with AChRAb-negative generalized MG had
      MuSK-MG. CONCLUSIONS: Clinical characteristics of MG in Sri Lanka are similar to
      other populations. Complementing the RIA with CBA increases the diagnostic power
      of detecting pathogenic autoantibodies.

PMID- 24929652
TI  - N-acetylcysteine improves established monocrotaline-induced pulmonary
      hypertension in rats.
AB  - BACKGROUND: The outcome of patients suffering from pulmonary arterial
      hypertension (PAH) are predominantly determined by the response of the right
      ventricle to the increase afterload secondary to high vascular pulmonary
      resistance. However, little is known about the effects of the current available
      or experimental PAH treatments on the heart. Recently, inflammation has been
      implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known
      safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We
      therefore hypothesized that NAC could reduce the severity of pulmonary
      hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation
      and preserving pulmonary vascular system and right heart function. METHODS:
      Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14-28)
      were evaluated at day 28 following MCT for hemodynamic parameters (right
      ventricular systolic pressure, mean pulmonary arterial pressure and cardiac
      output), right ventricular hypertrophy, pulmonary vascular morphometry, lung
      inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic
      cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. RESULTS:
      The treatment with NAC significantly decreased pulmonary vascular remodeling,
      lung inflammation, and improved total pulmonary resistance (from 0.71 +/- 0.05
      for MCT group to 0.50 +/- 0.06 for MCT + NAC group, p < 0.05). Right ventricular
      function was also improved with NAC treatment associated with a significant
      decrease in cardiomyocyte hypertrophy (625 +/- 69 vs. 439 +/- 21 MUm2 for MCT and
      MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 +/- 0.8 vs. 8.8
      +/- 0.1% for MCT and MCT + NAC group respectively, p < 0.001). CONCLUSIONS:
      Through its immuno-modulatory and cardioprotective properties, NAC has beneficial
      effect on pulmonary vascular and right heart function in experimental PH.

PMID- 24929653
TI  - Modelling human protein interaction networks as metric spaces has potential in
      disease research and drug target discovery.
AB  - BACKGROUND: We have recently shown by formally modelling human protein
      interaction networks (PINs) as metric spaces and classified proteins into zones
      based on their distance from the topological centre that hub proteins are
      primarily centrally located. We also showed that zones closest to the network
      centre are enriched for critically important proteins and are also functionally
      very specialised for specific 'house keeping' functions. We proposed that
      proteins closest to the network centre may present good therapeutic targets.
      Here, we present multiple pieces of novel functional evidence that provides
      strong support for this hypothesis. RESULTS: We found that the human PINs has a
      highly connected signalling core, with the majority of proteins involved in
      signalling located in the two zones closest to the topological centre. The
      majority of essential, disease related, tumour suppressor, oncogenic and approved
      drug target proteins were found to be centrally located. Similarly, the majority
      of proteins consistently expressed in 13 types of cancer are also predominantly
      located in zones closest to the centre. Proteins from zones 1 and 2 were also
      found to comprise the majority of proteins in key KEGG pathways such as MAPK
      signalling, the cell cycle, apoptosis and also pathways in cancer, with very
      similar patterns seen in pathways that lead to cancers such as melanoma and
      glioma, and non-neoplastic diseases such as measles, inflammatory bowel disease
      and Alzheimer's disease. CONCLUSIONS: Based on the diversity of evidence
      uncovered, we propose that when considered holistically, proteins located
      centrally in the human PINs that also have similar functions to existing drug
      targets are good candidate targets for novel therapeutics. Similarly, since
      disease pathways are dominated by centrally located proteins, candidates
      shortlisted in genome scale disease studies can be further prioritized and
      contextualised based on whether they occupy central positions in the human PINs.

PMID- 24929654
TI  - HIF-1alpha genetic variants and protein expression confer the susceptibility and
      prognosis of gliomas.
AB  - To investigate the role of HIF-1alpha genetic polymorphism of c.1772C>T and
      c.1790G>A in the incidence and prognosis of gliomas in a Chinese cohort, a total
      of 387 gliomas patients and 437 age- and sex-matched healthy controls were
      recruited. The genetic polymorphism of c.1772C>T and c.1790G>A was determined. We
      found that the genotype distribution at c.1772C>T showed significant difference
      between patients and controls. Multivariable analyses showed a significantly
      higher risk for gliomas in 1772TT genotype carriers (odds ratio 2.68, with CC as
      reference). In addition, we also found a significantly higher risk for grade III
      + IV gliomas was observed in 1772TT genotype carriers (odds ratio 2.21, with CC
      as reference). The overall survival rates in patients with 1772TT or 1772CT
      genotype were markedly lower compared with patients with CC (both P < 0.01). Our
      in vitro studies revealed that HIF-1alpha regulates the proliferation, migration
      and invasion of human glioma U251 cells. This study suggests that the c.1772C>T
      polymorphisms may be used as a molecular marker for gliomas occurrence, grades
      and clinical outcome in gliomas patients. 

PMID- 24929657
TI  - Deltoid muscle injury scratched by an osteophyte on the greater tuberosity of the
      humeral head: an unusual cause of shoulder pain.
AB  - Few reports to date have discussed acute deltoid muscle injury, including partial
      or complete deltoid muscle detachment from its origin. The present report
      describes a different pathomechanism and clinical manifestations of deltoid
      muscle injury. A 52-year-old man experienced acute severe pain in the right
      shoulder as a result of abrupt elevation of the arm. The deltoid muscle had
      apparently been scratched by an osteophyte on the greater tuberosity. After
      arthroscopic excision of the osteophyte, the symptoms resolved completely.

PMID- 24929656
TI  - A cadaveric study of the anterolateral ligament: re-introducing the lateral
      capsular ligament.
AB  - PURPOSE: The purpose of this study was to verify and characterize the anatomical
      properties of the anterolateral capsule, with the aim of establishing a more
      accurate anatomical description of the anterolateral ligament (ALL). Furthermore,
      microscopic analysis of the tissue was performed to determine whether the ALL can
      morphologically be classified as ligamentous tissue, as well as reveal any
      potential functional characteristics. METHODS: Three different modalities were
      used to validate the existence of the ALL: magnetic resonance imagining (MRI),
      anatomical dissection, and histological analysis. Ten fresh-frozen cadaveric knee
      specimens underwent MRI, followed by anatomical dissection which allowed
      comparison of MRI to gross anatomy. Nine additional fresh-frozen cadaveric knees
      (19 total) were dissected for a further anatomical description. Four specimens
      underwent H&E staining to look at morphological characteristics, and one specimen
      was analysed using immunohistochemistry to locate peripheral nervous innervation.
      RESULTS: The ALL was found in all ten knees undergoing MRI and all nineteen knees
      undergoing anatomical dissection, with MRI being able to predict its
      corresponding anatomical dissection. The ALL was found to have bone-to-bone
      attachment points from the lateral femoral epicondyle to the lateral tibia, in
      addition to a prominent meniscal attachment. Histological sectioning showed ALL
      morphology to be characteristic of ligamentous tissue, having dense, regularly
      organized collagenous bundles. Immunohistochemistry revealed a large network of
      peripheral nervous innervation, indicating a potential proprioceptive role.
      CONCLUSION: From this study, the ALL is an independent structure in the
      anterolateral compartment of the knee and may serve a proprioceptive role in knee
      mechanics.

PMID- 24929659
TI  - No differences in clinical outcomes between fixed- and mobile-bearing computer
      assisted total knee arthroplasties and no correlations between navigation data
      and clinical scores.
AB  - PURPOSE: The theoretical advantages of mobile-bearing (MB) designs over the
      conventional fixed bearings (FBs) for total knee arthroplasty (TKA) have not been
      proved yet through clinical studies. The aim of the study was to test whether the
      MB design has advantages in terms of better clinical outcomes when compared to
      FB. Furthermore, the relationships between intra-operative obtained implant
      positioning data and the clinical scores were analysed. METHODS: A total of 99
      patients were randomized into the FB or the MB group. All patients received the
      same posterior cruciate retaining implants and were operated with the use of a
      computer-assisted navigation system. The clinical outcomes of both groups were
      compared pre-operatively, at 1 year, and at a mean follow-up time of 4 years
      after surgery. RESULTS: The MB implants showed no advantages over the FB when
      comparing the Knee Society Scores, the Oxford Score, the range of movement (ROM)
      and pain intensity of the patients in both groups at 1 and 4 years after surgery.
      There were no relationships between the computer navigation data and the clinical
      scores. CONCLUSIONS: In view of the 4-year results, there is no evidence to
      support the recommendation of one design over the other in terms of better
      clinical outcome scores, higher ROM or lower pain rates. Long-term follow-up
      results may be necessary, including survival rates. Further research comparing
      different TKA designs should also include standardized performance-based tests.
      LEVEL OF EVIDENCE: Prospective study (Randomized controlled trial with adequate
      statistical power to detect differences), Level I.

PMID- 24929658
TI  - Gross anatomical and dimensional characteristics of the proximal hamstring
      origin.
AB  - PURPOSE: The current study was undertaken to better define the gross anatomical
      and dimensional characteristics of the proximal hamstring origin. METHODS: Twelve
      paired whole-lower extremities from six embalmed cadavers were dissected. The
      gross anatomy of the proximal hamstrings was studied. With the tendons attached
      to the ischial tuberosity, the width and thickness of each tendon was measured 1
      cm distally to their origin, and the distance from the most proximal border of
      the common origin of the semitendinosus (ST) and long head of the biceps (LB) to
      their distal junction was assessed. After removal of the hamstring group, the
      shape, orientation, and dimension of the tendon footprints were determined.
      RESULTS: One cadaver demonstrated unique anatomy, which was considered as an
      anatomic variant and was therefore excluded from the study group. The ST and LB
      had a common origin on the posterolateral aspect of the ischial tuberosity
      (ST/LB), whereas the semimembranosus (SM) had a separated origin at the
      anterolateral aspect. The mean distance from the most proximal border of the
      ST/LB origin to the distal junction was 10.0 +/- 1.3 cm. The shape of both
      footprints was longitudinal-oval, with the longitudinal axes of the SM and ST/LB
      footprints parallel aligned. Mean tendon width was 3.4 +/- 0.5 cm for the common
      ST/LB complex and 4.2 +/- 0.9 cm for the SM (p = 0.009). The corresponding values
      for tendon thickness were 1.0 +/- 0.3 cm (ST/LB) and 0.8 +/- 0.2 cm (SM),
      respectively (n.s.). Mean footprint length was 3.9 +/- 0.4 cm for ST/LB and 4.5
      +/- 0.5 cm for SM (p = 0.002). The corresponding values for footprint height were
      1.4 +/- 0.5 cm (ST/LB) and 1.2 +/- 0.3 cm (SM), respectively (n.s.). CONCLUSION:
      The ST and LB had a common origin, whereas the SM originated separately. The site
      of origin of both tendons was the lateral aspect of the ischial tuberosity, with
      the SM footprint lying directly anterior to the footprint of the ST/LB complex.
      The footprint of the SM was significantly wider than the footprint of the ST/LB.
      The reported gross anatomic findings and dimensions may aid surgeons in anchor
      placement at the anatomical attachment site, thereby facilitating anatomic
      hamstring repair. In addition, the provided data may improve diagnosis and
      conservative treatment of proximal hamstring tendinopathy, since detailed
      knowledge about the normal anatomy is crucial for recognizing tendon
      abnormalities and for several conservative treatment modalities such as shockwave
      application or ultrasound-guided injections.

PMID- 24929655
TI  - Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the
      blood-brain barrier.
AB  - The cannabinoid (CB) receptors are the main targets of the cannabinoids, which
      include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the
      last few years, accumulated evidence has suggested a role of the CB receptors in
      neuroprotection. The blood-brain barrier (BBB) is an important brain structure
      that is essential for neuroprotection. A link between the CB receptors and the
      BBB is thus likely, but this possible connection has only recently gained
      attention. Cannabinoids and the BBB share the same mechanisms of neuroprotection
      and both protect against excitotoxicity (CB1), cell death (CB1), inflammation
      (CB2) and oxidative stress (possibly CB independent)-all processes that also
      damage the BBB. Several examples of CB-mediated protection of the BBB have been
      found, such as inhibition of leukocyte influx and induction of amyloid beta
      efflux across the BBB. Moreover, the CB receptors were shown to improve BBB
      integrity, particularly by restoring the tightness of the tight junctions. This
      review demonstrated that both CB receptors are able to restore the BBB and
      neuroprotection, but much uncertainty about the underlying signaling cascades
      still exists and further investigation is needed. 

PMID- 24929660
TI  - Maintenance of postmitotic neuronal cell identity.
AB  - The identity of specific cell types in the nervous system is defined by the
      expression of neuron type-specific gene batteries. How the expression of such
      batteries is initiated during nervous system development has been under intensive
      study over the past few decades. However, comparatively little is known about how
      gene batteries that define the terminally differentiated state of a neuron type
      are maintained throughout the life of an animal. Here we provide an overview of
      studies in invertebrate and vertebrate model systems that have carved out the
      general and not commonly appreciated principle that neuronal identity is
      maintained in postmitotic neurons by the sustained, and often autoregulated,
      expression of the same transcription factors that initiate terminal
      differentiation in a developing organism. Disruption of postmitotic maintenance
      mechanisms may result in neuropsychiatric and neurodegenerative conditions. 

PMID- 24929662
TI  - Can a deprivation index be used legitimately over both urban and rural areas?
AB  - BACKGROUND: Although widely used, area-based deprivation indices remain sensitive
      to urban-rural differences as such indices are usually standardised around
      typical urban values. There is, therefore, a need to determine to what extent
      available deprivation indices can be used legitimately over both urban and rural
      areas. METHODS: This study was carried out in Brittany, France, a relatively
      affluent region that contains deep rural areas. Among the 1,736 residential
      census block groups (IRIS) composing the Brittany region, 1,005 (57.9%) are
      rural. Four deprivation indices were calculated: two scores (Carstairs and
      Townsend) developed in the UK and two more recent French measures (Havard and
      Rey). Two standardisation levels were considered: all of the IRIS and only the
      urban IRIS of the region. Internal validity (Kappa coefficients and entropy
      values) and external validity (relationship with colorectal cancer screening
      [CCS] attendance) were investigated. RESULTS: Regardless of the deprivation
      measure used, wealthy areas are mostly clustered in the West and at the outskirts
      of major towns. Carstairs and Rey scores stand out by all evaluation criteria,
      capturing both urban and rural deprivation. High levels of agreements were found
      across standardisation levels (kappa = 0.96). The distributions of deprivation
      scores were balanced across urban and rural areas, and high Shannon entropy
      values were observed in the capital city (>=0.93). Similar and significant
      negative trends were observed between CCS attendance and both deprivation
      indices, independent of the degree of urbanisation. CONCLUSIONS: These results
      provide support, despite potential sociological objections, for the use of a
      compromise index that would facilitate comparisons and interpretations across
      urban and rural locations in public health research.

PMID- 24929661
TI  - Lesions of prefrontal cortex reduce attentional modulation of neuronal responses
      and synchrony in V4.
AB  - It is widely held that the frontal eye field (FEF) in prefrontal cortex (PFC)
      modulates processing in visual cortex with attention, although the evidence that
      it is necessary is equivocal. To help identify critical sources of attentional
      feedback to area V4, we surgically removed the entire lateral PFC, including the
      FEF, in one hemisphere and transected the corpus callosum and anterior commissure
      in two macaques. This deprived V4 of PFC input in one hemisphere while keeping
      the other hemisphere intact. In the absence of PFC, attentional effects on
      neuronal responses and synchrony in V4 were substantially reduced and the
      remaining effects of attention were delayed in time, indicating a critical role
      for PFC. Conversely, distracters captured attention and influenced V4 responses.
      However, because the effects of attention in V4 were not eliminated by PFC
      lesions, other sources of top-down attentional control signals to visual cortex
      must exist outside of PFC. 

PMID- 24929665
TI  - Lessons from the cigarette wars in the battle against obesity.

PMID- 24929664
TI  - Autophagy and the immune function in aging.
AB  - Just when you thought that you had heard it all about autophagy-the conserved
      cellular process that mediates turnover of cellular constituents in the lysosomes
      - studies keep coming out highlighting new types of autophagy, new functions for
      autophagy or even new autophagy-independent roles for the proteins associated
      with this process. The field of immunology has been riding the autophagic wave
      since the beginning of its revival; first due to its role in the host defense
      against pathogens, and more recently through the better understanding of the
      unique characteristics and functions of different autophagic pathways in immune
      cells. Here, we describe some of these new functions that are tightening the
      connection between autophagy and acquired or innate immunity and their
      malfunctioning with age.

PMID- 24929663
TI  - Ammonia, like K(+), stimulates the Na(+), K(+), 2 Cl(-) cotransporter NKCC1 and
      the Na(+),K(+)-ATPase and interacts with endogenous ouabain in astrocytes.
AB  - Brain edema during hepatic encephalopathy or acute liver failure as well as
      following brain ischemia has a multifactorial etiology, but it is a dangerous and
      occasionally life-threatening complication because the brain is enclosed in the
      rigid skull. During ischemia the extracellular K(+) concentration increases to
      very high levels, which when energy becomes available during reperfusion
      stimulate NKCC1, a cotransporter driven by the transmembrane ion gradients
      established by the Na(+),K(+)-ATPase and accumulating Na(+), K(+) and 2 Cl(-)
      together with water. This induces pronounced astrocytic swelling under pathologic
      conditions, but NKCC1 is probably also activated, although to a lesser extent,
      during normal brain function. Redistribution of ions and water between extra- and
      intracellular phases does not create brain edema, which in addition requires
      uptake across the blood-brain barrier. During hepatic encephalopathy and acute
      liver failure a crucial factor is the close resemblance between K(+) and NH4(+)
      in their effects not only on NKCC1 and Na(+),K(+)-ATPase but also on Na(+),K(+)
      ATPase-induced signaling by endogenous ouabains. These in turn activate
      production of ROS and nitrosactive agents which slowly sensitize NKCC1,
      explaining why cell swelling and brain edema generally are delayed under
      hyperammonemic conditions, although very high ammonia concentrations can cause
      immediate NKCC1 activation.

PMID- 24929666
TI  - Glutamate-gated chloride channel subunit cDNA sequencing of Cochliomyia
      hominivorax (Diptera: Calliphoridae): cDNA variants and polymorphisms.
AB  - The New World screwworm (NWS) Cochliomyia hominivorax (Coquerel) is one of the
      major myiasis-causing flies that injures livestock and leads to losses of ~US$
      2.7 billions/year in the Neotropics. Ivermectin (IVM), a macrocyclic lactone
      (ML), is the most used preventive insecticide for this parasite and targets the
      glutamate-gated chloride (GLUCLalpha) channels. Several authors have associated
      altered GluClalpha homologues to MLs resistance in invertebrates, although
      studies about resistance in NWS are limited to other genes. Here, we aimed to
      characterise the NWS GluClalpha (ChGluClalpha) cDNA and to search for alterations
      associated with IVM resistance in NWS larvae from a bioassay. The open reading
      frame of the ChGluClalpha comprised 1,359 bp and encoded a sequence of 452 amino
      acids. The ChGluClalpha cDNAs of the bioassay larvae showed different sequences
      that could be splice variants, which agree with the occurrence of alternative
      splicing in GluClalpha homologues. In addition, we found cDNAs with premature
      stop codons and the K242R SNP, which occurred more frequently in the surviving
      larvae and was located close to mutation (L256F) involved in ML resistance.
      Although these alterations were in low frequency, the ChGluClalpha sequencing
      will allow further studies to find alterations in the gene of resistant natural
      populations.

PMID- 24929667
TI  - Contrast-enhanced ultrasonography for evaluation of cystic renal mass: in
      comparison to contrast-enhanced CT and conventional ultrasound.
AB  - PURPOSE: To assess the value of contrast-enhanced ultrasonography (CEUS) in
      evaluating cystic renal lesions compared with conventional ultrasound (US) and
      contrast-enhanced computed tomography (CECT). METHODS: One hundred and three
      patients with complex cystic renal masses underwent preoperative US and CEUS,
      among which 70 conducted CECT at our institution. The images were analyzed with
      the number of septa, septa and wall thickness and the presence of solid
      component, and final diagnosis was made. RESULTS: In malignancies, CEUS
      demonstrated more septa, thicker wall or septa, and more solid components than US
      and CECT. CEUS permitted categorization of 51.7% (30/58) and 28.6% (10/35) of
      malignant tumors in higher grade than by US and CECT, respectively. In benign
      lesions, CEUS detected more septa than CECT and correctly diagnosed benign cysts
      which appeared as solid lesions in US. CEUS permitted downgrading of 71.1%
      (32/45) and 17.1% (6/35) of benign lesions compared to US and CECT. The
      diagnostic performance of CEUS was better than US for benign cystic lesions. The
      phenomenon that solid-like component by US did not enhance by CEUS was a strong
      predictor of benign disease, with a positive predictive value (PPV) of 100%.
      Enhancement of solid, soft tissue by CEUS was highly predictive of malignancy,
      with a PPV of 100%. CONCLUSIONS: CEUS was superior to US and CECT in visualizing
      the number of septa septa and wall thickness, and the presence of solid component
      of cystic renal lesions. CEUS may play a similar role to CECT in the diagnosis of
      renal cystic lesions, and better than US.

PMID- 24929668
TI  - Mass-forming cholangiocarcinoma and adenocarcinoma of unknown primary: can they
      be distinguished on liver MRI?
AB  - PURPOSE: To determine MR features suggestive of mass-forming cholangiocarcinoma
      (CCA) or liver metastases of adenocarcinoma of unknown primary (AUP), and to
      compare the ability of two experienced radiologists to establish the correct
      diagnosis. MATERIALS AND METHODS: 61 patients with CCA or AUP, with MRIs were
      placed into two groups: population 1, 28 patients with certain diagnosis of
      either CCA or AUP; and population 2, 33 patients with uncertain diagnosis. Using
      population 1 with known diagnosis, two investigators formulated imaging criteria
      for CCA or AUP, which represented phase 1 of the study. In phase 2, two
      independent radiologists categorized the patients in populations 1 and 2 as CCA
      or AUP using the formulated criteria. This categorization was compared with the
      patient medical records and pathologist review. Findings were tested for
      statistical significance. RESULTS: In phase 1, solitary lesion, multifocal
      lesions with dominant lesion, capsule retraction, and porta hepatis
      lymphadenopathy were features of CCA; multifocal lesions with similar size, and
      ring enhancement were features of AUP. The number of lesions, capsule retraction,
      and early tumor enhancement pattern were observed to be significant features (P <
      0.05). In phase 2, agreement between the two radiologists was good (k = 0.663).
      For population 1, the agreement was good (k = 0.659), and was fair for population
      2 (k = 0.293). Concordance between the two radiologists, medical record, and the
      pathologist was found in 41/61 (67%) patients. CONCLUSION: Distinctive features
      of CCA and AUP are identifiable on MRI images, which may aid the radiologist to
      establish the correct diagnosis.

PMID- 24929670
TI  - Improved elongation factor-1 alpha-based vectors for stable high-level expression
      of heterologous proteins in Chinese hamster ovary cells.
AB  - BACKGROUND: Establishing highly productive clonal cell lines with constant
      productivity over 2-3 months of continuous culture remains a tedious task
      requiring the screening of tens of thousands of clonal colonies. In addition,
      long-term cultivation of many candidate lines derived in the absence of drug
      selection pressure is necessary. Expression vectors based on the elongation
      factor-1 alpha (EEF1A) gene and the dihydrofolate reductase (DHFR) selection
      marker (with separate promoters) can be used to obtain highly productive
      populations of stably transfected cells in the selection medium, but they have
      not been tested for their ability to support target gene amplification under
      gradually increasing methotrexate pressure. RESULTS: We have modified EEF1A-based
      vectors by linking the DHFR selection marker to the target gene in the
      bicistronic RNA, shortening the overall plasmid size, and adding an Epstein-Barr
      virus terminal repeat fragment (EBVTR) element. Presence of the EBVTR element
      increased the rate of stable transfection by the plasmid by 24 times that of the
      EBVTR-minus control and improved the rate of methotrexate-driven gene
      amplification. The mean expression level of the enhanced green fluorescent
      protein (eGFP) used herein as a model protein, increased up to eight-fold using a
      single round of amplification in the case of adherent colonies formation and up
      to 4.5-fold in the case of suspension polyclonal cultures. Several eGFP
      expressing cell populations produced using vectors with antibiotic resistance
      markers instead of the DHFR marker were compared with each other. Stable
      transfection of Chinese hamster ovary (CHO) DG44 cells by the p1.2-Hygro-eGFP
      plasmid (containing a hygromycin resistance marker) generated highest eGFP
      expression levels of up to 8.9% of the total cytoplasmic protein, with less than
      5% of the cell population being eGFP-negative. CONCLUSIONS: The p1.1 vector was
      very effective for stable transfection of CHO cells and capable of rapid MTX
      driven target gene amplification, while p1.2-Hygro achieved similar eGFP
      expression levels as p1.1. The set of vectors we have developed should speed-up
      the process of generating highly productive clonal cell lines while substantially
      decreasing the associated experimental effort.

PMID- 24929669
TI  - microRNA-128a dysregulation in transgenic Huntington's disease monkeys.
AB  - BACKGROUND: Huntington's Disease (HD) is a progressive neurodegenerative disorder
      with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs)
      have recently been implicated as epigenetic regulators of neurological disorders,
      however, their role in HD pathogenesis is not well defined. Here we study
      transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate
      model of the disease. RESULTS: In this report, 11 miRNAs were found to be
      significantly associated (P value < 0.05) with HD in the frontal cortex of the HD
      monkeys. We further focused on one of those candidates, miR-128a, due to the
      corresponding disruption in humans and mice with HD as well as its intriguing
      lists of gene targets. miR-128a was downregulated in our HD monkey model by the
      time of birth. We then confirmed that miR-128a was also downregulated in the
      brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our
      studies confirmed a panel of canonical HD signaling genes regulated by miR-128a,
      including HTT and Huntingtin Interaction Protein 1 (HIP1). CONCLUSION: Our
      studies found that miR-128a may play a critical role in HD and could be a viable
      candidate as a therapeutic or biomarker of the disease.

PMID- 24929671
TI  - Fusarium keratitis at a tertiary eye care centre in India.
AB  - The aim of the study was to report the clinical and microbiological profiles of
      Fusarium keratitis. In this single-centre, retrospective, non-comparative case
      series, 47 laboratory-confirmed cases of keratitis caused by Fusarium species
      treated at the L V Prasad Eye Institute, Bhubaneswar, India, between November
      2006 and October 2009, were reviewed. The analysis included predisposing factors,
      clinical characteristics, microbiological findings, treatment and outcome. Forty
      seven samples of 47 patients were included in the study. The mean age of the 47
      patients was 46 +/- 17 years. Twelve eyes had a history of injury. Corneal
      scraping could not be done in one of the cases due to large perforation. Fungal
      filaments were detected in corneal scraping in 41 cases, and in three cases
      microconidia were observed in microscopy. Fusarium solani was the most common
      species (44.7 %). All three cases where microconidia were present in smear were
      identified as F. solani in culture. The mean time to positive culture was 2.4 +/-
      1.5 days. Twenty-three patients underwent adjunctive surgical procedure. Visual
      acuity of <20/200 at presentation and final follow-up was noted in 80.9 and 51.4
      % patients, respectively. One-half (23/47) of the patients had improvement in
      visual acuity. Fusarium keratitis may present after trauma without any satellite
      lesion, and the response to medical therapy is generally poor. Rapid diagnosis
      can be made by smear examination of corneal scrapings in a majority of the cases
      and confirmed by culture within 2-3 days. Presence of microconidia in smear
      examination may be suggestive of F. solani.

PMID- 24929672
TI  - Gender differences in affective sharing and self-other distinction during
      empathic neural responses to others' sadness.
AB  - Self-other distinction, the separation between self and other, is a prerequisite
      for empathy through which individuals share another individual's feelings. Prior
      research suggests that females are better at recognizing and sharing others'
      emotions, whereas males perform better at self-other distinction. It is unclear,
      however, whether this superiority in the self-other distinction occurs in males
      throughout the experience of empathy or only at some stages of the empathic
      process. The present study utilized event-related potentials (ERPs) to
      investigate this issue. In two separate experimental tasks, subjects were
      instructed to either judge the emotions shown on a face (other-task) or evaluate
      their own affective responses to the emotions shown on a face (self-task). The
      results of the other-task revealed that unlike males, females displayed increased
      P2 (190-240 ms) amplitudes to sad expressions compared with neutral expressions.
      This finding might be associated with an improved ability to recognize and share
      the emotions of others in females. In contrast, only males exhibited larger P2
      amplitudes to sad expressions compared with neutral expressions during the self
      task. This awareness of one's own emotions in response to another individual
      might reflect a distinction between the self and the other at an early stage in
      males. At the late cognitive controlled stage, gender differences became weak.
      However, the emotion effects in each task for both genders were positively
      correlated with self-reported cognitive empathy, which was indexed by the
      perspective taking (PT) and fantasy (FS) subscale, but not with affective
      empathy. 

PMID- 24929673
TI  - Current role of rufinamide in the treatment of childhood epilepsy: literature
      review and treatment guidelines.
AB  - PURPOSE: The literature on the efficacy and safety of rufinamide in childhood
      onset epilepsy syndromes currently includes approximately 600 paediatric
      patients. This paper summarizes the views of a panel of experienced European
      epileptologists with regard to the current role of rufinamide in the treatment of
      childhood epilepsies. RESULTS: Rufinamide is effective in decreasing the seizure
      frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic
      seizures. It might consequently be preferred to other drugs as a second-line
      treatment for LGS when drop-attacks are frequent. The mean responder rate in the
      published studies is 38% with seizure freedom achieved in 2.4% of patients.
      Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS.
      It can be also effective as adjunctive therapy in children and adolescents with
      drug-resistant partial seizures. The available data suggest that rufinamide has
      an acceptable risk/benefit ratio with quite a low risk of aggravating seizures.
      Common adverse effects (somnolence, nausea and vomiting) are usually mild and
      self-limiting; they are more frequently observed during titration than in the
      maintenance phase, suggesting that low escalation rates might be associated with
      fewer adverse effects. Rufinamide appears to have a favourable cognitive profile
      compared with other antiepileptic drugs. CONCLUSION: Rufinamide is only approved
      for adjunctive treatment of seizures associated with LGS in children 4 years of
      age and older. There are very few data on rufinamide treatment at the onset of
      LGS or early in the course of the disorder; whether early treatment will improve
      outcome has yet to be determined.

PMID- 24929674
TI  - Chromosome analysis in embryos from young patients with previous parity.
AB  - This study included 173 young couples of proven fertility who had previously
      undergone preimplantation genetic screening for chromosomes X and Y for family
      balancing. Several months later, when the outcome of the pregnancies was already
      known, the blastomeres from the corresponding embryos transferred were reanalysed
      by fluorescence in-situ hybridization (FISH) for chromosomes 13, 16, 18, 21, 22
      with the aim of investigating correlation with embryo viability and the level of
      FISH sensitivity (embryos confirmed to be euploid). According to the results,
      informative in 152 couples, the proportion of euploid embryos was significantly
      lower in 53 nonpregnant women when compared with 99 women with term pregnancy
      (49% versus 75% respectively, P < 0.001). In addition, in 21 nonpregnant
      patients, all embryos transferred were found to be chromosomally abnormal. The
      level of FISH sensitivity was calculated in the group of term pregnancies where
      the number of euploid embryos was expected to exceed or match with the number of
      babies born. The resulting false-negative rate was 4.0% per patient and 1.9% per
      embryo. These findings confirmed the limited prediction power of embryo
      morphology on implantation but also the relevance of chromosomal abnormalities in
      causing embryo demise. 

PMID- 24929676
TI  - Pneumonitis and pulmonary fibrosis associated with breast cancer treatments.
AB  - To review the available published data regarding the incidence, mechanisms of
      pathogenesis, clinical presentations and management of pneumonitis caused by anti
      cancer treatments (radiotherapy (RT) and systemic agents) that are included in
      the guidelines of the treatment of breast cancer (BC) and address the issues on
      the current grading classification of pneumonitis. A literature search was
      performed between July and October 2013 using PubMed for papers published from
      January 1989 to October 2013. Any clinical trial, case report, case series, meta
      analysis or systematic review that reported on pulmonary toxicity of any BC
      therapeutic modality was included (only papers published in English). Most of
      anticancer treatments currently used in the management of BC may induce some
      degree of pneumonitis that is estimated to have an incidence of 1-3 %. There is
      an obvious distinction between chemotherapy- and targeted treatment-related lung
      toxicity. Moreover, the current classification of pneumonitis needs to be
      modified as there is a clear diversity in grade 2. As pneumonitis is relatively
      common and reported as side effect of new anticancer agents, physicians need to
      be aware of the clinical and radiological manifestations of drug- and RT-induced
      toxicities in patients with BC. A key recommendation is the subdivision of grade
      2 cases to two subgroups. We provide an algorithm, along with real life cases as
      managed in the breast Unit of Royal Marsden Hospital, with the aim to guide
      physicians in managing all possible eventualities that may come across in
      clinical practise.

PMID- 24929675
TI  - Ado-trastuzumab emtansine-associated telangiectasias in metastatic breast cancer:
      a case series.
AB  - Treatment of HER2-positive metastatic breast cancer with ado-trastuzumab
      emtansine (T-DM1), a novel antibody-drug conjugate, has resulted in both improved
      progression-free and overall survival. Recognition and treatment of diverse
      adverse events related to T-DM1 is critical for safety and tolerability. The most
      frequent adverse events with T-DM1 include fatigue, diarrhea, anemia, elevated
      transaminases, and mild-to-moderate hemorrhagic events, which are thought to be
      related to induced thrombocytopenia. Here, we present five case series of
      cutaneous and mucosal telangiectasias, definitely related to T-DM1. The
      development of telangiectasias represents a newly recognized adverse effect of T
      DM1. We provide description and timing of the telangiectasias and review the
      mechanisms that may explain the formation of these vascular lesions in
      association with T-DM1. Further, we describe associated bleeding events and
      propose that induced telangiectasias could represent an additional cause of T-DM1
      associated hemorrhage.

PMID- 24929678
TI  - Conjoint occurrence of GABAB receptor antibodies in Lambert-Eaton myasthenic
      syndrome with antibodies to the voltage gated calcium channel.
AB  - Antibodies (abs) to the GABAB receptor have been recently found to be responsible
      for immune-mediated encephalitis with dominant seizures. They are in
      approximately 50% of cases associated with small-cell lung cancer (SCLC). GABAB
      receptors are mainly located in the hippocampus, thalamus and cerebellum in the
      presynaptic and postsynaptic regions of synapses. The main function of these
      receptors is to reduce activity states of neurons. In some instances, GABAB
      receptor abs in these patients were accompanied by other antibodies, among them
      VGCC abs (Lancaster et al., 2010, Boronat et al., 2011). VGCC abs cause
      paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) by reduction of
      presynaptic VGCCs (Titulaer et al., 2011). In the domain of CNS disease, VGCC abs
      have been found in association with paraneoplastic cerebellar ataxia (Mason et
      al., 1997) and rarely and at low titres also in other paraneoplastic
      encephalopathies together with Hu abs (Lennon et al., 1995). It has been a long
      standing debate if abs in paraneoplastic conditions associate rather with the
      neurological syndrome or the tumour. Here, we describe the conjoint occurrence of
      abs to the GABAB receptor and to the VGCC in a patient with SCLC presenting only
      symptoms of the peripheral nervous system giving another example of the latter
      hypothesis.

PMID- 24929677
TI  - Recurrent read-through fusion transcripts in breast cancer.
AB  - Read-through fusion transcripts that result from the splicing of two adjacent
      genes in the same coding orientation are a recently discovered type of chimeric
      RNA. We sought to determine if read-through fusion transcripts exist in breast
      cancer. We performed paired-end RNA-seq of 168 breast samples, including 28
      breast cancer cell lines, 42 triple negative breast cancer primary tumors, 42
      estrogen receptor positive (ER+) breast cancer primary tumors, and 56 non
      malignant breast tissue samples. We analyzed the sequencing data to identify
      breast cancer associated read-through fusion transcripts. We discovered two
      recurrent read-through fusion transcripts that were identified in breast cancer
      cell lines, confirmed across breast cancer primary tumors, and were not detected
      in normal tissues (SCNN1A-TNFRSF1A and CTSD-IFITM10). Both fusion transcripts use
      canonical splice sites to join the last splice donor of the 5' gene to the first
      splice acceptor of the 3' gene, creating an in-frame fusion transcript. Western
      blots indicated that the fusion transcripts are translated into fusion proteins
      in breast cancer cells. Custom small interfering RNAs targeting the CTSD-IFITM10
      fusion junction reduced expression of the fusion transcript and reduced breast
      cancer cell proliferation. Read-through fusion transcripts between adjacent genes
      with different biochemical functions represent a new type of recurrent molecular
      defect in breast cancer that warrant further investigation as potential
      biomarkers and therapeutic targets. Both breast cancer associated fusion
      transcripts identified in this study involve membrane proteins (SCNN1A-TNFRSF1A
      and CTSD-IFITM10), which raises the possibility that they could be breast cancer
      specific cell surface markers.

PMID- 24929679
TI  - Intermittent clobazam prophylaxis in hot water epilepsy is safe and effective: a
      prospective study.
AB  - PURPOSE: To evaluate the role of intermittent prophylaxis with clobazam in the
      management of HWE in a long-term prospective study. MATERIAL AND METHODS: Two
      hundred and sixty patients [M:F - 194:66] with HWE were recruited. Patients were
      divided into: (a) 'HWE alone' (n=198) - received intermittent clobazam
      prophylaxis, 1-11/2h prior to hot water head bath (group A); (b) 62 patients
      (20.4%) with 'HWE with spontaneous seizures were treated with continuous AEDs
      along with intermittent clobazam therapy (group B). RESULTS: Patients (n=198) in
      group A was followed for mean of 17.6 +/- 10.6 months (range: 3-57). One hundred
      and forty seven patients (74.2%) had excellent response with complete seizure
      freedom with clobazam therapy while 12 (6.1%) had >75% reduction in seizure
      frequency. Remaining 39 (19.7%) required additional standard AED along with
      clobazam and 18 patients among them developed spontaneous/unprovoked seizure at
      follow up of 6.7 +/- 4.1 months. Forty five patients in group B were seizure free
      while on continuous AEDs. CONCLUSIONS: Intermittent clobazam prophylaxis prior to
      head water bath might be a preferred mode of treatment of pure HWE. Additional
      AEDs are required if they have associated non-reflex unprovoked seizure.

PMID- 24929680
TI  - Manufacture and characterization of a yogurt-like beverage made with oat flakes
      fermented by selected lactic acid bacteria.
AB  - This study aimed at investigating the suitability of oat flakes for making
      functional beverages. Different technological options were assayed, including the
      amount of flakes, the inoculum of the starter and the addition of enzyme
      preparations. The beverage containing 25% (wt/wt) of oat flakes and fermented
      with L. plantarum LP09 was considered optimal on the basis of sensory and
      technological properties. The enzyme addition favored the growth of the starter,
      shortened the time needed to reach pH4.2 to ca. 8h, and favored a decrease of the
      quotient of fermentation. Fermentation increased the polyphenols availability and
      the antioxidant activity (25 and 70% higher, respectively) and decreased the
      hydrolysis index in vitro. Sensory analyses showed that fermented oat flakes
      beverage had the typical features of a yogurt-like beverage, enhancing the
      overall intensity of odor and flavor compared to the non-fermented control.
      Selection of proper processing and fermentation condition allowed the obtainment
      of a beverage with better nutritional and sensory properties. 

PMID- 24929681
TI  - Survey of Canadian retail pork chops and pork livers for detection of hepatitis E
      virus, norovirus, and rotavirus using real time RT-PCR.
AB  - Over the past 15 years, hepatitis E virus (HEV), norovirus (NoV), and rotavirus
      (RV) have been hypothesized to be potentially zoonotic; swine and pork have been
      suggested as possible human infection sources for all 3 viruses. Our objective
      was to estimate HEV, NoV, and RV prevalence and load on Canadian retail pork
      chops and livers. Using the Canadian Integrated Program for Antimicrobial
      Resistance Surveillance (CIPARS) sampling platform, pork livers (n=283) and chops
      (n=599) were collected, processed, and assayed for the 3 viruses by four
      collaborating federal laboratories using validated real time reverse
      transcriptase polymerase chain reactions (qRT-PCR). Follow-up qRT-PCR estimating
      viral load in genomic copies/g was followed by nested classical RT-PCR and
      isolate sequencing of a partial segment of the ORF2 gene. Local alignments were
      performed using MUSCLE (Multiple Sequence Comparison by Log-Expectation); a
      phylogenetic tree was created. Twenty-five livers and 6 chops were classified
      'positive' (thresholds for viral RNA detected in both replicates of the assay) or
      'suspect' (thresholds detected in one of two replicates) for HEV. Follow-up qRT
      PCR detected HEV on 16 livers, 0 chops, and nested classical RT-PCR, on 14 livers
      and 0 chops. Initial qRT-PCR classified 12 chops 'suspect' for NoV. Follow-up qRT
      PCR detected viral RNA on only one sample with thresholds greater than 40 in both
      replicates. No amplicon was yielded, and therefore no isolate was sequenced from
      this sample. Partial ORF2 genes from 14 HEV isolates were sequenced, and compared
      via sequence identity and phylogenetic analysis with selected human case isolates
      listed in NCBI-GenBank. Overall, HEV prevalence on retail pork was comparable
      with other published reports.

PMID- 24929683
TI  - Combined effect of chitosan and water activity on growth and fumonisin production
      by Fusarium verticillioides and Fusarium proliferatum on maize-based media.
AB  - The objectives of the present study were to determine the in vitro efficacy of
      chitosan (0.5, 1.0, 2.0 and 3.0mg/mL) under different water availabilities
      (0.995, 0.99, 0.98, 0.96 and 0.93) at 25 degrees C on lag phase, growth rate and
      fumonisin production by isolates of Fusarium verticillioides and Fusarium
      proliferatum. The presence of chitosan affected growth and fumonisin production,
      and this effect was dependent on the dose and aW treatment used. The presence of
      chitosan increased the lag phase, and reduced the growth rate of both Fusarium
      species significantly at all concentrations used, especially at 0.93 aW. Also,
      significant reduction of fumonisin production was observed in both Fusarium
      species at all conditions assayed. The present study has shown the combined
      effects of chitosan and aW on growth and fumonisin production by the two most
      important Fusarium species present on maize. Low molecular weight (Mw) chitosan
      with more than 70% of degree of deacetylation (DD) at 0.5mg/mL was able to
      significantly reduce growth rate and fumonisin production on maize-based media,
      with maximum levels of reduction in both parameters obtained at the highest doses
      used. As fumonisins are unavoidable contaminants in food and feed chains, their
      presence needs to be reduced to minimize their effects on human and animal health
      and to diminish the annual market loss through rejected maize. In this scenario
      post-harvest use of chitosan could be an important alternative treatment.

PMID- 24929682
TI  - Identification of beer-spoilage bacteria using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Applicability of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) for identification of beer-spoilage bacteria was
      examined. To achieve this, an extensive identification database was constructed
      comprising more than 4200 mass spectra, including biological and technical
      replicates derived from 273 acetic acid bacteria (AAB) and lactic acid bacteria
      (LAB), covering a total of 52 species, grown on at least three growth media.
      Sequence analysis of protein coding genes was used to verify aberrant MALDI-TOF
      MS identification results and confirmed the earlier misidentification of 34 AAB
      and LAB strains. In total, 348 isolates were collected from culture media
      inoculated with 14 spoiled beer and brewery samples. Peak-based numerical
      analysis of MALDI-TOF MS spectra allowed a straightforward species identification
      of 327 (94.0%) isolates. The remaining isolates clustered separately and were
      assigned through sequence analysis of protein coding genes either to species not
      known as beer-spoilage bacteria, and thus not present in the database, or to
      novel AAB species. An alternative, classifier-based approach for the
      identification of spoilage bacteria was evaluated by combining the identification
      results obtained through peak-based cluster analysis and sequence analysis of
      protein coding genes as a standard. In total, 263 out of 348 isolates (75.6%)
      were correctly identified at species level and 24 isolates (6.9%) were
      misidentified. In addition, the identification results of 50 isolates (14.4%)
      were considered unreliable, and 11 isolates (3.2%) could not be identified. The
      present study demonstrated that MALDI-TOF MS is well-suited for the rapid, high
      throughput and accurate identification of bacteria isolated from spoiled beer and
      brewery samples, which makes the technique appropriate for routine microbial
      quality control in the brewing industry. 

PMID- 24929684
TI  - Influence of acetylation degree and molecular weight of homogeneous chitosans on
      antibacterial and antifungal activities.
AB  - The results given in the literature are conflicting when considering the
      relationship between antimicrobial activity and chitosan characteristics. To be
      able to clarify, we prepared fifteen homogeneous chitosans with different
      acetylation degrees (DA) and molecular weights (MW) by reacetylation of a fully
      deacetylated chitin under homogeneous conditions. They were tested at different
      pH values for their antimicrobial activities against four Gram-negative bacteria
      (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella
      typhi), four Gram-positive bacteria (Staphylococcus aureus, Bacillus cereus,
      Enterococcus faecalis and Micrococcus luteus) and three fungi (Aspergillus niger,
      Fusarium oxysporum and Alternaria solani). Chitosans markedly inhibited growth of
      most bacteria and fungi tested, although the inhibitory effect depends on the
      type of microorganism and on the chitosan characteristics (DA and MW) with
      minimum inhibitory concentrations in the range of 0.001 to 0.1 w%. Considering
      chitosan efficiency on bacteria, our series of data clearly show that the lower
      DA and the lower pH give the larger efficiency. Antibacterial activity was
      further enhanced for Gram-negative bacteria with decreasing MW, whereas, opposite
      effect was observed with the Gram-positive. Concerning the antifungal activity,
      the influence of chitosan characteristics was dependent on the particular type of
      fungus. Fungal growth decreased with increasing MW for F. oxysporum and
      decreasing DA for A. solani, but no MW or DA dependences were observed with A.
      niger.

PMID- 24929685
TI  - Inactivation of Alicyclobacillus acidoterrestris spores in aqueous suspension and
      on apples by neutral electrolyzed water.
AB  - Alicyclobacillus acidoterrestris can be difficult to control in fruit juices as
      their spores survive juice pasteurization temperatures and may subsequently
      germinate and grow. Contaminated fruits can be regarded as a major source of
      spoilage caused by A. acidoterrestris in fruit juices. The objective of this
      study was to evaluate the efficacy of neutral electrolyzed water (NEW) in
      reducing the number of A. acidoterrestris spores in aqueous suspension and on
      surface-inoculated apples. Its effectiveness was compared with that of sodium
      hypochlorite (SH) solutions at free chlorine concentrations of 50 and 200mg/L.
      Viable spore counts in test suspensions were significantly (P<0.05) reduced after
      exposure to NEW (200mg/L free chlorine) for 1 min. However, NEW (50mg/L free
      chlorine) and SH solutions were unable to significantly (P>0.05) reduce the
      number of viable spore during the same exposure period. More than 5 log reduction
      in spore counts was achieved by NEW solution containing 200mg/L free chlorine
      after 5 min of exposure. Exposure to NEW solutions for 3 min yielded more than 4
      log reductions in the number of viable spores on apple surfaces. At the same
      concentrations of free chlorine, NEW was three to more than ten-fold effective
      than SH in reducing viability of A. acidoterrestris spores in aqueous suspension
      and on apple surfaces. This finding suggests that NEW can be considered as an
      effective disinfectant for the control of A. acidoterrestris on fruits.

PMID- 24929686
TI  - A portable system for foot biomechanical analysis during gait.
AB  - Modeling the foot is challenging due to its complex structure compared to most
      other body segments. To analyze the biomechanics of the foot, portable devices
      have been designed to allow measurement of temporal, spatial, and pedobarographic
      parameters. The goal of this study was to design and evaluate a portable system
      for kinematic and dynamic analysis of the foot during gait. This device consisted
      of a force plate synchronized with four cameras and integrated into a walkway.
      The complete system can be packaged for transportation. First, the measurement
      system was assessed using reference objects to evaluate accuracy and precision.
      Second, nine healthy participants were assessed during gait trials using both the
      portable and Vicon systems (coupled with a force plate). The ankle and
      metatarsophalangeal (MP) joint angles and moments were computed, as well as the
      ground reaction force (GRF). The intra- and inter-subject variability was
      analyzed for both systems, as well as the inter-system variation. The accuracy
      and precision were, respectively 0.4 mm and 0.4 mm for linear values and 0.5
      degrees  and 0.6 degrees  for angular values. The variability of the portable and
      Vicon systems were similar (i.e., the inter-system variability never exceeded 2.1
      degrees , 0.081 Nmkg(-1) and 0.267 Nkg(-1) for the angles, moments and GRF,
      respectively). The inter-system differences were less than the inter-subject
      variability and similar to the intra-subject variability. Consequently, the
      portable system was considered satisfactory for biomechanical analysis of the
      foot, outside of a motion analysis laboratory.

PMID- 24929687
TI  - Cancer services to 2025 in New Zealand--investing in research-driven quality
      care.

PMID- 24929688
TI  - Surgery for cancer: less and less for more and more patients.

PMID- 24929689
TI  - Twelve years' experience of sentinel lymph node biopsy for melanoma at a rural
      New Zealand hospital.
AB  - AIM: To document the false-negative sentinel lymph node biopsy (SLNB) rate for
      melanoma patients at a rural NZ hospital and the likelihood of further nodal
      involvement on completion lymph node dissection (CLND). METHODS: All patients
      undergoing SLNB for melanoma at this centre were identified from the study
      period. Basic demographics along with histological data of both the primary
      lesion and SLNB were collated. Local and regional recurrences were recorded as
      was mortality. RESULTS: Between January 2000 and July 2012, 95 patients underwent
      SLNB for melanoma. Ten patients (11%) underwent CLND after positive SLNB. A
      further two patients had a median of two additional nodes involved (range 1-3).
      After a median follow-up period of 65 months (range 47-112), 6 patients suffered
      nodal recurrence where previously a negative SLNB had been harvested, giving a
      false-negative rate of 38%. Recurrence occurred a median of 16 months after WLE
      and SLNB. CONCLUSION: A high false negative-negative rate was observed in this
      study. For those with a positive SLNB, a further 20% have further nodal
      involvement on CLND.

PMID- 24929690
TI  - Screening for colorectal cancer and prostate cancer: challenges for New Zealand.
AB  - AIM: Prostate cancer and colorectal cancer are the most commonly registered
      cancers in New Zealanders and among the five most commonly registered cancers
      worldwide, but the balance of benefits and harms, and therefore appropriate
      screening policies, for these cancers differ. We aimed to compare the potential
      benefits and harms of screening for prostate cancer and colorectal cancer to aid
      prioritisation in New Zealand. METHOD: Relevant reports from randomised
      controlled trials and systematic reviews of prostate cancer and colorectal cancer
      screening were reviewed to obtain estimates of the potential benefits and harms
      of screening for prostate cancer and colorectal cancer. RESULTS: The balance of
      potential benefits and harms of screening is better for colorectal cancer
      screening than for prostate cancer screening. For colorectal cancer, the balance
      of benefits and harms is better for flexible sigmoidoscopy screening than for
      faecal occult blood screening. CONCLUSION: In New Zealand, colorectal cancer
      screening should be a priority. Challenges include colonoscopy capacity, and
      decisions about the most appropriate screening modality.

PMID- 24929691
TI  - Influence of age and site of disease on lymph node yield in colorectal cancer.
AB  - AIM: Colorectal cancer (CRC) is the second-leading cause of cancer death in New
      Zealand. Lymph node yield (LNY) is an independent prognostic factor in CRC and 12
      or more lymph nodes in the resected specimen is the current recommended standard,
      regardless of age or site of disease. The aim of this study was to examine the
      effect of age and site of the disease on LNY. METHOD: Patients undergoing
      elective surgery for CRC at Dunedin Hospital between 1995 and 2012, who enrolled
      in studies involving prospective data and tissue collection, were included in the
      current study. The relationship between LNY and demographic and pathological
      variables including age, sex, tumour location and stage were investigated.
      RESULTS: 824 patients were included (mean age 70.5 years, 51% female). The mean
      (SD) LNY was 17.9 (10.1).There was a weak but significant negative correlation
      between age and LNY (r=-0.08; p=0.024) that was more evident in patients with
      right-sided tumours (r=0.18; p=0.001). Right-sided tumours also had a higher LNY
      (mean 20.5) than left colon (mean 16.8) and rectal cancer (mean 14.6) (p<0.001).
      Overall the mean LNY reduced by 1 for every 7 years advancement in age.
      CONCLUSION: LNY is higher in right-sided colon cancer and reduces with age.
      Further research should consider whether the recommended standard for LNY in the
      specimen should take account of age and tumour location.

PMID- 24929692
TI  - Paediatric ovarian lesions--the experience at Starship Children's Hospital, New
      Zealand.
AB  - AIM: To review the experience of paediatric ovarian masses at Starship Children's
      Hospital (Auckland, New Zealand). Primarily to assess the range of pathology, the
      presenting features, and the surgical management of these lesions. METHODS: A
      search of the hospital surgical pathology database was carried out to identify
      patients less than 16 years in whom ovarian tissue was submitted for pathological
      analysis during the 12 year period from January 2000 to December 2011. A
      retrospective review of the medical records was carried out. RESULTS: 244 ovarian
      masses in 219 patients were identified. 99 of these were neoplastic with 19
      (7.8%) being malignant and an additional four (1.6%) borderline malignant lesions
      (borderline epithelial tumours). Mature cystic teratoma was the commonest
      neoplastic lesion (55.6%). Patients who presented with acute abdominal pain were
      more commonly found to have non-neoplastic lesions than neoplastic lesions (71.5%
      vs 46.9%, p<0.0001), and those that presented with a palpable mass were more
      commonly found to have a neoplastic lesion (24.0% vs 3.3%, p<0.0001).
      Laparoscopic surgery was performed in 41.6% of all patients. Ovary conserving
      surgery was performed in 56.6% of all patients, though only 32.3% of patients
      with neoplastic lesions. CONCLUSION: This study provides important insight into
      the range of ovarian pathology encountered in a New Zealand paediatric
      population. Most of the ovarian lesions in paediatric age groups are benign.
      Ovarian sparing surgery is recommended. In cases of ovarian torsion, malignancy
      in this series and in the literature is less than 2%. This review highlights that
      paediatric surgical units have vast experience to deal with ovarian pathology in
      paediatric age groups.

PMID- 24929693
TI  - Thyroid cancer in Pacific women in New Zealand.
AB  - AIM: To describe trends in incidence rates of thyroid cancer in New Zealand
      between 1981-2004 with a particular focus on Pacific women. METHOD: Linked census
      cancer registration data was used to calculate age standardised cancer incidence
      rates for thyroid cancer. Both trends over time amongst Pacific women, and
      differences in rates between Pacific and European/Other women in New Zealand,
      were assessed. RESULTS: Rates of thyroid cancer in New Zealand were higher for
      women than men. The highest rates of thyroid cancer in were observed amongst
      Pacific women with a pooled age-standardised incidence rate of 18.5/100,000
      (95%CI 14.6-22.4/100,000) compared to 5.2/100,000 (95% 4.8-5.5/100,000) for
      European/Other; SRR 3.58 (95%CI 2.87-4.47). Sparse data mean it is difficult to
      clearly identify a trend over time for Pacific women but European women
      experienced a 73% increase from 4.0/100,000 (95%CI 3.3-4.6/100,000) in 1981=1986
      to 6.9/100,000 (95%CI 5.9-7.8/100,000) in 2001-2004 (Ptrend=0.05). CONCLUSIONS:
      Pacific women in New Zealand have the highest rates of thyroid cancer among
      resident ethnic groups. Risk was highest for Pacific women over 45 years of age.
      More research needs to be done looking at which specific ethnicities are driving
      rates of thyroid cancer in New Zealand and whether the risk is influenced by
      birthplace and age at migration to New Zealand.

PMID- 24929694
TI  - Rectal cancer: future directions and priorities for treatment, research and
      policy in New Zealand.
AB  - New Zealand has one of the highest incidences of rectal cancer in the world, and
      its optimal management requires a multidisciplinary approach. A National Rectal
      Cancer Summit was convened in August 2013 to discuss management of rectal cancer
      in the New Zealand context, to highlight controversies and discuss domestic
      priorities for the future. This paper summarises the priorities for treatment,
      research and policy for rectal cancer services in New Zealand identified as part
      of the Summit in August. The following priorities were identified: - Access to
      high-quality information for service planning, review of outcomes, identification
      of inequities and gaps in provision, and quality improvement; - Engagement with
      the entire sector, including private providers; - Focus on equity; - Emerging
      technologies; - Harmonisation of best practice; - Importance of multidisciplinary
      team meetings. In conclusion, improvements in outcomes for patients with rectal
      cancer in New Zealand will require significant engagement between policy makers,
      providers, researchers, and patients in order to ensure equitable access to high
      quality treatment, and strategic incorporation of emerging technologies into
      clinical practice. A robust clinical information framework is required in order
      to facilitate monitoring of quality improvements and to ensure that equitable
      care is delivered.

PMID- 24929695
TI  - Anorectal melanoma: not a haemorrhoid.
AB  - AIM: Melanoma of the anorectum is a rare malignancy which is particularly
      aggressive compared to cutaneous melanoma. Due to its presenting symptoms,
      location and rarity there is often a delay in diagnosis. The purpose of this
      paper is to raise awareness of anorectal melanoma in New Zealand by presenting
      our institution's experience of four cases. METHODS: The presentation, management
      and outcomes of four cases are described. A review of the literature surrounding
      anorectal melanoma was also carried out. RESULTS: The four cases (3 male, 1
      female, aged 30-87 years) all presented with haemorrhoidal symptoms of anal
      discomfort and/or outlet rectal bleeding. Three patients had metastatic disease
      at presentation, and the remaining patient was found to have a concurrent
      lymphoma which was treated with chemotherapy before he underwent excision of the
      melanoma. Surgical excision is the mainstay of treatment and recent literature
      suggests transanal excision of the primary tumour to have equivalent overall
      survival to abdominoperineal resection. CONCLUSION: Anorectal melanoma is rare
      tumour with a poor prognosis. Patients are commonly misdiagnosed as having
      haemorrhoids; therefore a high index of suspicion is needed to enable early
      diagnosis. Metastatic disease is common at presentation, and the key prognostic
      indicator. Local control can be obtained with transanal excision, avoiding the
      morbidity of abdominoperineal resection. Adjuvant therapies available at present
      provide little survival advantage.

PMID- 24929696
TI  - Pseudotumours and IgG4-related disease: a case report.
AB  - We report a case of a patient presenting with abdominal pain, weight loss and CT
      imaging showing mass lesions in the chest and abdomen associated with
      lymphadenopathy. He was diagnosed as having IgG4-related disease and responded
      well to steroid treatment.

PMID- 24929697
TI  - Missed melanomas.

PMID- 24929698
TI  - Update from the NZ Familial GI Cancer Service.

PMID- 24929699
TI  - Measurement of cigarette butt litter accumulation within city bus shelters.

PMID- 24929700
TI  - Does one size fit all? National elective operation hospital discharge rates may
      not be a good fit for all New Zealand district health boards.

PMID- 24929701
TI  - Predictors of primary Achilles tendon ruptures.
AB  - BACKGROUND: The Achilles tendon is the strongest tendon in the human body. The
      incidence of Achilles tendon ruptures appears to be increasing. OBJECTIVES: The
      aim of this review was to systematically summarize predictors influencing
      Achilles tendon rupture (ATR) risk. METHODS: A systematic literature search was
      performed of reported determinants influencing the ATR risk. Studies were
      eligible if there was: (i) description of determinants predicting ATR; (ii) an
      outcome defined as ATR; (iii) any study design with at least ten adults included
      with ATR; (iv) use of statistical tests regarding differences between patients
      with an ATR and healthy controls; (v) a full text article available; (vi) an
      article written in English, German or Dutch. Quality assessment was done using a
      standardized criteria set. Best-evidence synthesis was performed. RESULTS: We
      included 31 studies, of which two (6.5%) were considered high-quality studies.
      Moderate evidence was found for increased ATR risk and decreased fibril size of
      Achilles tendon. CONCLUSION: Based on the results of this systematic review there
      is moderate evidence that decreased tendon fibril size increases the ATR risk.
      There is limited evidence for many other factors, some of which are modifiable,
      such as increased body weight, oral corticosteroid use and quinolone use and
      living in an urban area, and therefore may be of interest in future studies.
      Furthermore, these results showed that more high-quality studies are needed for
      evaluating the determinants influencing the ATR risk.

PMID- 24929702
TI  - A decision model to estimate the cost-effectiveness of intensity modulated
      radiation therapy (IMRT) compared to three dimensional conformal radiation
      therapy (3DCRT) in patients receiving radiotherapy to the prostate bed.
AB  - BACKGROUND: Intensity modulated radiation therapy (IMRT) is a radiation therapy
      technology that facilitates the delivery of an improved dose distribution with
      less dose to surrounding critical structures. This study estimates the longer
      term effectiveness and cost-effectiveness of IMRT in patients post radical
      prostatectomy. METHODS: A Markov decision model was developed to calculate the
      incremental quality adjusted life years (QALYs) and costs of IMRT compared with
      three dimensional conformal radiation therapy (3DCRT). Costs were estimated from
      the perspective of the Australian health care system. RESULTS: IMRT was both more
      effective and less costly than 3DCRT over 20 years, with an additional 20 QALYs
      gained and over $1.1 million saved per 1000 patients treated. This result was
      robust to plausible levels of uncertainty. CONCLUSIONS: IMRT was estimated to
      have a modest long term advantage over 3DCRT in terms of both improved
      effectiveness and reduced cost. This result was reliant on clinical judgement and
      interpretation of the existing literature, but provides quantitative guidance on
      the cost effectiveness of IMRT whilst long term trial evidence is awaited.

PMID- 24929707
TI  - MiR-205 inhibits cell apoptosis by targeting phosphatase and tensin homolog
      deleted on chromosome ten in endometrial cancer Ishikawa cells.
AB  - BACKGROUND: MicroRNAs (miRNAs) are frequently dysregulated in human cancers and
      can act as either potent oncogenes or tumor suppressor genes. In the present
      study, we intend to prove that the gene PTEN (phosphatase and tensin homolog
      deleted on chromosome ten) is a target gene of miR-205 and to investigate the
      suppressive effects on PTEN transcriptional activity by enhancing miR-205
      expression in endometrial cancer Ishikawa cells. METHODS: Using Ishikawa cells as
      model systems, we up-regulated miR-205 expression by transient transfection with
      miR-205 mimics. A luciferase reporter assay, qRT-PCR and western blotting assays
      were used to verify whether PTEN is a direct target of miR-205. Meanwhile, the
      modulatory role of miR-205 in the AKT (protein kinase B) pathway was evaluated by
      determining the AKT phosphorylation. As a biological counterpart, we investigated
      cell apoptosis using flow cytometry. RESULTS: Our data indicate that miR-205 down
      regulates the expression of PTEN through direct interaction with the putative
      binding site in the 3'-untranslated region (3'-UTR) of PTEN. Moreover, we
      documented the functional interactions of miR-205 and PTEN, which have a
      downstream effect on the regulation of the AKT pathway, explaining, at least in
      part, the inhibitory effects on Ishikawa cell apoptosis of enhancing miR-205
      expression. CONCLUSIONS: For the first time, we demonstrate that the expression
      of PTEN is directly regulated by miR-205 in endometrial cancer cells and leads
      the inhibition of cellular apoptosis. This relationship could be targeted for new
      therapeutic strategies for endometrial cancer.

PMID- 24929703
TI  - Allograft rejection and tubulointerstitial fibrosis in human kidney allografts:
      interrogation by urinary cell mRNA profiling.
AB  - Because the kidney allograft has the potential to function as an in-vivo flow
      cytometer and facilitate the access of immune cells and kidney parenchymal cells
      in to the urinary space, we hypothesized that mRNA profiling of urinary cells
      offers a noninvasive means of assessing the kidney allograft status. We overcame
      the inherent challenges of urinary cell mRNA profiling by developing pre
      amplification protocols to compensate for low RNA yield from urinary cells and by
      developing robust protocols for absolute quantification mRNAs using RT-PCR
      assays. Armed with these tools, we undertook first single-center studies urinary
      cell mRNA profiling and then embarked on the multicenter Clinical Trials in Organ
      Transplantation-04 study of kidney transplant recipients. We report here our
      discovery and validation of diagnostic and prognostic biomarkers of acute
      cellular rejection and of interstitial fibrosis and tubular atrophy (IF/TA). Our
      urinary cell mRNA profiling studies, in addition to demonstrating the feasibility
      of accurate diagnosis of acute cellular rejection and IF/TA in the kidney
      allograft, advance mechanistic and potentially targetable biomarkers.
      Interventional trials, guided by urinary cell mRNA profiles, may lead to
      personalized immunosuppression in recipients of kidney allografts.

PMID- 24929708
TI  - The differential effects of surgical harm in elderly populations. Does the adage:
      "they tolerate the operation, but not the complications" hold true?
AB  - BACKGROUND: Elderly patients are thought to tolerate surgical complications
      poorly because of low physiologic reserve. The purpose of the study was to
      evaluate the differential effects of surgical harm in patients over 80 years old.
      METHODS: Three years of data from a harm-reduction campaign were used to identify
      inpatient surgeries performed on patients older than 50. The rates of harm,
      death, cost, and length of stay (LOS) were analyzed using SPSS 21 (IBM, New York,
      NY). RESULTS: A total of 22,710 patients were identified. Rates of harm and
      mortality increased with increasing age. Harmed patients over age 80 had
      increased mortality (9.5% vs 7%), but lower cost, intensive care unit days, and
      LOS versus those aged 50 to 80. Linear regression showed increased cost with harm
      ($24,000) and decreased cost with age above 80 (-$7,000). CONCLUSIONS: In the
      elderly surgical population, there is more harm and harm events are associated
      with higher mortality rates, but less additional cost and LOS. Differing goals or
      aggressiveness of care may explain cost avoidance in the elderly.

PMID- 24929710
TI  - Evaluation of indirect impedance for measuring microbial growth in complex food
      matrices.
AB  - The suitability of indirect impedance to accurately measure microbial growth in
      real food matrices was investigated. A variety of semi-solid and liquid food
      products were inoculated with Bacillus cereus, Listeria monocytogenes,
      Staphylococcus aureus, Lactobacillus plantarum, Pseudomonas aeruginosa,
      Escherichia coli, Salmonella enteriditis, Candida tropicalis or Zygosaccharomyces
      rouxii and CO2 production was monitored using a conductimetric (Don Whitely
      R.A.B.I.T.) system. The majority (80%) of food and microbe combinations produced
      a detectable growth signal. The linearity of conductance responses in selected
      food products was investigated and a good correlation (R(2) >= 0.84) was observed
      between inoculum levels and times to detection. Specific growth rate estimations
      from the data were sufficiently accurate for predictive modeling in some cases.
      This initial evaluation of the suitability of indirect impedance to generate
      microbial growth data in complex food matrices indicates significant potential
      for the technology as an alternative to plating methods. 

PMID- 24929709
TI  - Antifungal effect of antimicrobial peptides (AMPs LR14) derived from
      Lactobacillus plantarum strain LR/14 and their applications in prevention of
      grain spoilage.
AB  - The concern for food safety has led to an increased interest in the development
      of novel antimicrobials. Keeping this aim in mind, we have investigated the
      antifungal effect of antimicrobial peptides (AMPs LR14) produced by Lactobacillus
      plantarum strain LR/14 against four spoilage fungi, namely, Aspergillus niger,
      Rhizopus stolonifer, Mucor racemosus and Penicillium chrysogenum. Interestingly,
      all the four fungi were inhibited, suggesting that AMPs LR14 exhibited anti
      fungal property. The peptides inhibited both, the spore germination and hyphal
      growth, however, the former stage was found to be more susceptible. The hyphal
      extensions were also inhibited in a dose-dependent manner. Viability test of
      treated spores confirmed the fungicidal activity of AMPs LR14. AMPs LR14 were
      also studied for the prevention of wheat grain spoilage under storage. Unhygienic
      conditions in damp godowns and store-houses, lead to loss of food grains and make
      them unfit for human consumption due to microbial deterioration. The treatment of
      wheat seeds with AMPs LR14 prevented fungal growth even after a prolonged storage
      under laboratory conditions for ~2.5 years. The carbohydrate and protein content
      of the AMPs LR14-treated seeds denoted no significant loss, but the seed
      viability was affected as germination was retarded. Such studies have not been
      reported for any bacteriocin/AMP to the best of our knowledge. 

PMID- 24929711
TI  - Characterization of extended-spectrum beta-lactamases-producing Salmonella
      strains isolated from retail foods in Shaanxi and Henan Province, China.
AB  - Extended-spectrum beta-lactamases (ESBL)-producing Salmonella enterica have been
      reported worldwide. However, research on foodborne ESBL-producing Salmonella has
      been rarely conducted. One hundred and thirty eight ceftriaxone or/and
      cefoperazone-resistant Salmonella strains recovered from retail foods in Shaanxi
      and Henan Province, China, were screened for ESBL. The ESBL-producing strains
      were further characterized for antimicrobial resistance, pulse field gel
      electrophoresis (PFGE) profiles, and the presence of blaTEM, blaSHV, blaOXA,
      blaCTX-M, and blaPSE. The transferability of ESBL encoding genes to a susceptible
      Escherichia coli strain was also investigated. Thirty (21.7%) isolates were
      identified as ESBL positive and belonged to S. enterica serovars Indiana, Shubra,
      Typhimurium, and Enteritidis. S. Indiana and S. Shubra isolates were firstly
      identified in ESBL-producing strains. Great genetic diversity was seen among
      these ESBL-producing strains. Nucleotide sequence analysis revealed that blaTEM
      1B was the only ESBL-encoding gene among the genes tested and was detected in 26
      of 30 strains and was carried in the conjugative plasmids. The blaTEM-1B gene was
      transferable through conjugation at rates ranging from 4.71 * 10(-7) to 7.55 *
      10(-6) transconjugant per recipient cell. This study provides the evidence of
      foodborne ESBL-producing Salmonella, and the transferability of plasmid harboring
      ESBL-encoding genes could possibly contribute to the dissemination of ESBL. 

PMID- 24929712
TI  - Development of a rapid detection system for opportunistic pathogenic Cronobacter
      spp. in powdered milk products.
AB  - Certain species of the genus Cronobacter are considered opportunistic pathogens,
      but their detection in milk products according to ISO/TS 22964 may take up to six
      days. The aim of this study was to develop a fast and sensitive PCR-based
      detection system for these species including enrichment, DNA-isolation and
      detection by real-time PCR, using the outer membrane protein gene ompA as a
      target. The assay was successfully validated using type strains of the genus
      Cronobacter, as well as 18 strains of closely related genera as controls. A total
      of 40 Cronobacter spp. food isolates yielded positive results, while the food
      matrix itself did not influence the PCR reaction. An equal detection limit as
      achieved with the ISO/TS 22964 method was established in this study, when 0.01
      CFU Cronobacter sakazakii DSM 4485(T) per gram powdered infant formula were
      successfully detected after 28 days of storage at ambient temperature. In
      comparison to the ISO/TS 22964 method, the method described here has an equal
      detection limit, but offers a specific detection at the genus level in an
      analysis time of 24 h. 

PMID- 24929713
TI  - Contribution of the NO-detoxifying enzymes HmpA, NorV and NrfA to nitrosative
      stress protection of Salmonella Typhimurium in raw sausages.
AB  - The antimicrobial action of the curing agent sodium nitrite (NaNO2) in raw
      sausage fermentation is thought to mainly depend on the release of cytotoxic
      nitric oxide (NO) at acidic pH. Salmonella Typhimurium is capable of detoxifying
      NO via the flavohemoglobin HmpA, the flavorubredoxin NorV and the periplasmic
      cytochrome C nitrite reductase NrfA. In this study, the contribution of these
      systems to nitrosative stress tolerance in raw sausages was investigated. In
      vitro growth assays of the S. Typhimurium 14028 deletion mutants DeltahmpA,
      DeltanorV and DeltanrfA revealed a growth defect of DeltahmpA in the presence of
      acidified NaNO2. Transcriptional analysis of the genes hmpA, norV and nrfA in the
      wild-type showed a 41-fold increase in hmpA transcript levels in the presence of
      150 mg/l acidified NaNO2, whereas transcription of norV and nrfA was not
      enhanced. However, challenge assays performed with short-ripened spreadable
      sausages produced with 0 or 150 mg/kg NaNO2 failed to reveal a phenotype for any
      of the mutants compared to the wild-type. Hence, none of the NO detoxification
      systems HmpA, NorV and NrfA is solely responsible for nitrosative stress
      tolerance of S. Typhimurium in raw sausages. Whether these systems act
      cooperatively, or if there are other yet undescribed mechanisms involved is
      currently unknown. 

PMID- 24929714
TI  - Characterization of Aspergillus section Flavi isolated from organic Brazil nuts
      using a polyphasic approach.
AB  - Brazil nut (Bertholletia excelsa), an important non-timber forest product from
      Amazonia, is commercialized in worldwide markets. The main importers of this nut
      are North America and European countries, where the demand for organic products
      has grown to meet consumers concerned about food safety. Thus, the precise
      identification of toxigenic fungi is important because the Brazil nut is
      susceptible to colonization by these microorganisms. The present study aimed to
      characterize by polyphasic approach strains of Aspergillus section Flavi from
      organic Brazil nuts. The results showed Aspergillus flavus as the main species
      found (74.4%), followed by Aspergillus nomius (12.7%). The potential
      mycotoxigenic revealed that 80.0% of A. flavus were toxin producers, 14.3% of
      which produced only aflatoxin B (AFB), 22.85% of which produced only
      cyclopiazonic acid (CPA), and 42.85% produced both them. All strains of A. nomius
      were AFB and AFG producers and did not produce CPA. There is no consensus about
      what Aspergillus species predominates on Brazil nuts. Apparently, the origin,
      processing, transport and storage conditions of this commodity influence the
      species that are found. The understanding about population of fungi is essential
      for the development of viable strategies to control aflatoxins in organic Brazil
      nuts. 

PMID- 24929716
TI  - Optimization of water curing for the preservation of chestnuts (Castanea sativa
      Mill.) and evaluation of microbial dynamics during process.
AB  - Chestnuts are very perishable fruits, whose quality may be compromised during
      postharvest handling. Damage can be caused both by insects and fungi. Water
      curing, a commonly used postharvest method, is based on soaking fruits in water
      typically for about one week. Factors that affect effectiveness of water curing
      have only been explained partially. A decrease in pH, likely imputable to a light
      fermentation caused by lactic acid bacteria, may inhibit the growth of moulds. In
      this study a Lactobacillus pentosus strain was selected for its ability to
      inhibit fungi, and used as a starter culture during water curing. As second goal,
      a reduction of the environmental impact of the process was evaluated by using
      water that had been re-cycled from a previous curing treatment. Experiments were
      performed on pilot as well as on farm scale. In all trials, microbial dynamics
      were evaluated by means of a polyphasic approach including conventional and
      molecular-based analyses. According to results, the employment of an adjunct
      culture appears as a very promising opportunity. Even if no reduction in the
      duration of the process was achieved, waters exhibited a minor microbial
      complexity and fruits did not lose the natural lustre after the process. 

PMID- 24929715
TI  - A Response Surface Methodology study on the role of factors affecting growth and
      volatile phenol production by Brettanomyces bruxellensis ISA 2211 in wine.
AB  - The present study was aimed at determining the effect of glucose, ethanol and
      sulphur dioxide on the growth and volatile phenol production by Brettanomyces
      bruxellensis in red wines using a response surface methodology approach. Sulphur
      dioxide proved to have a significant (p < 0.05) negative linear and quadratic
      effect on growth and 4-ethylphenol production. Concentrations of sulphur dioxide
      higher than 20 mg L(-1), at pH 3.50, induced immediate loss of cell culturability
      under growth permissive levels of ethanol. Under high ethanol concentrations (14%
      v/v), the lag phase increased from 3 to 10 days, growth being fully arrested at
      15% (v/v). Glucose up to 10 g L(-1) was found to be a significant factor
      (quadratic level) in biomass increase under low ethanol (<12.5% v/v) and low
      sulphite concentrations. However, when cells were inactivated by sulphur dioxide
      and ethanol, glucose (up to 10 g L(-1)) did not prevent cell death. Production of
      more than 50 MUg L(-1) day(-1) of 4-ethylphenol was only observed in the presence
      of high numbers (10(6) CFU mL(-1)) of culturable cells, being stimulated by
      increasing glucose concentrations. 

PMID- 24929717
TI  - Characterization of methicillin-resistant coagulase-negative staphylococci
      (MRCoNS) in retail meat.
AB  - This study was to understand the extent of methicillin-resistant coagulase
      negative staphylococci (MRCoNS) serving as a mecA reservoir in retail meat.
      MRCoNS were isolated from retail meat (beef, chicken, and turkey) in Detroit and
      characterized by sodA gene sequencing for species identification, staphylococcal
      cassette chromosome mec (SCCmec) typing, and pulsed-field gel electrophoresis
      (PFGE). Unique MRCoNS isolates recovered from 25 meat samples were comprised of
      Staphylococcus sciuri (n = 13), Staphylococcus fleuretti (n = 4), Staphylococcus
      lentus (n = 3), Staphylococcus epidermidis (n = 2), Staphylococcus vitulinus (n =
      1), Staphylococcus saprophyticus (n = 1) and Staphylococcus pasteuri (n = 1).
      Heterogeneous and composite SCCmec types, including I, III, IV, V, I + V and III
      + V were identified in 16 isolates. Same SCCmec types were recovered in different
      staphylococcal species and meat sources. Indistinguishable PFGE patterns were
      also observed in S. sciuri isolated from beef, chicken, and turkey, and with
      different SCCmec types. In conclusion, multiple CoNS species can serve as
      reservoirs for mecA. In addition to the clonal transmission of MRCoNS in meat,
      horizontal occurrence of SCCmec is observed in staphylococcal species. 

PMID- 24929718
TI  - Antimicrobial resistance of Listeria monocytogenes and Listeria innocua from meat
      products and meat-processing environment.
AB  - A total of 336 Listeria isolates from ready-to-eat (RTE) meat products and meat
      processing environments, consisting of 206 Listeria monocytogenes, and 130
      Listeria innocua isolates, were characterized by disc diffusion assay and minimum
      inhibitory concentration (MIC) values for antimicrobial susceptibility against
      twenty antimicrobials. Resistance to one or two antimicrobials was observed in 71
      L. monocytogenes isolates (34.5%), and 56 L. innocua isolates (43.1%). Multidrug
      resistance was identified in 24 Listeria isolates, 18 belonging to L. innocua
      (13.9%) and 6 to L. monocytogenes (2.9%). Oxacillin resistance was the most
      common resistance phenotype and was identified in 100% Listeria isolates. A
      medium prevalence of resistance to clindamycin (39.3% isolates) and low incidence
      of resistance to tetracycline (3.9% isolates) were also detected. Listeria
      isolates from RTE meat products displayed higher overall antimicrobial resistance
      (31.3%) than those from the environment (13.4%). All the strains assayed were
      sensitive to the preferred antibiotics used to treat listeriosis. Results showed
      that although antimicrobial resistance in L. monocytogenes still occurs at a low
      prevalence, L. innocua can form a reservoir of resistance genes which may
      transfer between bacterial species, including transference to organisms capable
      of causing disease in humans. 

PMID- 24929719
TI  - Listeria ivanovii ATCC 19119 strain behaviour is modulated by iron and acid
      stress.
AB  - It has been suggested that the rarity of human listeriosis due to Listeria
      ivanovii reflects not only host tropism factors but also the rare occurrence of
      this species in the environment, compared with Listeria monocytogenes. In the
      present study we evaluate the effects on the reference strain L. ivanovii ATCC
      19119 behaviour of two combined stresses, low iron availability and acid
      environment, that bacteria can encounter in the passage from saprophytic life to
      the host. In these conditions, L. ivanovii evidenced a different behaviour
      compared to L. monocytogenes exposed to similar conditions. L. ivanovii was not
      able to mount an acid tolerance response (ATR) even if, upon entry into the
      stationary phase in iron-loaded medium, growth phase-dependent acid resistance
      (AR) was evidenced. Moreover, bacteria grown in iron excess and acidic pH showed
      the higher invasion value in Caco-2 cells, even though it was not able to
      efficiently multiply. On the contrary, low iron and acidic conditions improved
      invasion ability in amniotic WISH cells. 

PMID- 24929720
TI  - Candida milleri species reveals intraspecific genetic and metabolic
      polymorphisms.
AB  - Candida milleri, together with Candida humilis, is the most representative yeast
      species found in type I sourdough ecosystems. In this work, comparison of the ITS
      region and the D1/D2 domain of 26S rDNA gene partial sequences, karyotyping,
      mtDNA-RFLP analysis, Intron Splice Site dispersion (ISS-PCR) and (GTG)5
      microsatellite analyses, assimilation test of different carbohydrates, and
      metabolome assessment by FT-IR analysis, were investigated in seventeen strains
      isolated from four different companies as well as in type strains CBS6897(T) and
      CBS5658(T). Most isolates were ascribed to C. milleri, even if a strong
      relatedness was confirmed with C. humilis as well, particularly for three
      strains. Genetic characterization showed a high degree of intraspecific
      polymorphism since 12 different genotypes were discriminated. The number of
      chromosomes varied from 9 to 13 and their size ranged from less than 0.3 to over
      2 Mbp. Phenotypic traits let to recognize 9 different profiles of carbon sources
      assimilation. FT-IR spectra from yeast cells cultivated in different media and
      collected at different growth phases revealed a diversity of behaviour among
      strains in accordance with the results of PCR-based fingerprinting. A clear
      evidence of the polymorphic status of C. milleri species is provided thus
      representing an important feature for the development of technological
      applications in bakery industries. 

PMID- 24929721
TI  - Prevention of late blowing defect by reuterin produced in cheese by a
      Lactobacillus reuteri adjunct.
AB  - In this study, reuterin-producing Lactobacillus reuteri INIA P572 was added to
      cheese as an adjunct culture together with 50 or 100 mM glycerol (required for
      reuterin production), with the aim of controlling Clostridium tyrobutyricum CECT
      4011 growth and preventing the late blowing defect (LBD) of cheese caused by this
      strain. L. reuteri survived cheese manufacture and produced reuterin in situ,
      detected at 6 and 24 h. However, the produced reuterin was enough to inhibit the
      growth of Clostridium, showing undetectable spore counts from day 30 onward and,
      therefore, to prevent cheese LBD during ripening (60 d, 14  degrees C). The
      acidification of these cheeses was not affected, although from day 14 they showed
      significantly lower lactococci counts than cheese made only with the starter
      (control cheese). Cheeses with LBD showed lower levels of lactic acid than
      control cheese and the formation of propionic and butyric acids, but cheeses with
      reuterin showed the same organic acids profile than control cheese. The cheese
      made with L. reuteri and 100 mM glycerol showed a light pink colour, not observed
      in the cheese made with L. reuteri and 50 mM glycerol. These results demonstrated
      a potent anti-clostridial activity of reuterin produced in an actual food product
      like cheese, and proved to be a novel approach to prevent LBD of cheese. 

PMID- 24929722
TI  - Bacillus cereus and Bacillus thuringiensis spores in Korean rice: prevalence and
      toxin production as affected by production area and degree of milling.
AB  - We determined the prevalence of and toxin production by Bacillus cereus and
      Bacillus thuringiensis in Korean rice as affected by production area and degree
      of milling. Rough rice was collected from 64 farms in 22 agricultural areas and
      polished to produce brown and white rice. In total, rice samples were broadly
      contaminated with B. cereus spores, with no effect of production area. The
      prevalence and counts of B. cereus spores declined as milling progressed.
      Frequencies of hemolysin BL (HBL) production by isolates were significantly (P <=
      0.01) reduced as milling progressed. This pattern corresponded with the presence
      of genes encoding the diarrheal enterotoxins. The frequency of B. cereus isolates
      positive for hblC, hblD, or nheB genes decreased as milling progressed. Because
      most B. cereus isolates from rice samples contained six enterotoxin genes, we
      concluded that B. cereus in rice produced in Korea is predominantly of the
      diarrheagenic type. The prevalence of B. thuringiensis in rice was significantly
      lower than that of B. cereus and not correlated with production area. All B.
      thuringiensis isolates were of the diarrheagenic type. This study provides
      information useful for predicting safety risks associated with B. cereus and B.
      thuringiensis in rough and processed Korean rice. 

PMID- 24929723
TI  - Are Enterococcus populations present during malolactic fermentation of red wine
      safe?
AB  - The aim of this study was the genetic characterisation and safety evaluation of
      129 Enterococcus isolates obtained from wine undergoing malolactic fermentation.
      Genetic characterisation by randomly amplified polymorphic DNA-PCR displayed 23
      genotypes. 25 isolates representative of all genotypes were identified as
      Enterococcus faecium by species-specific PCR and assayed for antibiotic
      resistance, presence of virulence genes and aminobiogenic capacity, both in
      decarboxylase medium and wine. The aminobiogenic capacity in wine was analysed in
      presence (assay 1) and absence (assay 2) of Oenococcus oeni CECT 7621. Resistance
      to tetracycline, cotrimoxazol, vancomycin and teicoplanin was exhibited by 96% of
      the strains, but none of them harboured the assayed virulence genes. All of the
      strains harboured the tyrosine decarboxylase (tdc) gene, while 44% were positive
      for tyramine in decarboxylase medium. Only five out of 25 strains survived in
      wine after seven days of incubation, and when concentrations of biogenic amines
      in wines were determined by HPLC, only those wines in which the five surviving
      strains occurred contained biogenic amines. Histamine, putrescine and cadaverine
      were detected in wines from both assays, although concentrations were higher in
      assay 2. Tyramine and phenylethylamine were detected only in absence of O. oeni.
      This research contributes for the knowledge of safety aspects of enterococci
      related to winemaking. 

PMID- 24929725
TI  - Atmospheric cold plasma inactivation of Escherichia coli, Salmonella enterica
      serovar Typhimurium and Listeria monocytogenes inoculated on fresh produce.
AB  - Atmospheric cold plasma (ACP) represents a potential alternative to traditional
      methods for non-thermal decontamination of foods. In this study, the
      antimicrobial efficacy of a novel dielectric barrier discharge ACP device against
      Escherichia coli, Salmonella enterica Typhimurium and Listeria monocytogenes
      inoculated on cherry tomatoes and strawberries, was examined. Bacteria were spot
      inoculated on the produce surface, air dried and sealed inside a rigid
      polypropylene container. Samples were indirectly exposed (i.e. placed outside
      plasma discharge) to a high voltage (70 kVRMS) air ACP and subsequently stored at
      room temperature for 24 h. ACP treatment for 10, 60 and 120 s resulted in
      reduction of Salmonella, E. coli and L. monocytogenes populations on tomato to
      undetectable levels from initial populations of 3.1, 6.3, and 6.7 log10
      CFU/sample, respectively. However, an extended ACP treatment time was necessary
      to reduce bacterial populations attached on the more complex surface of
      strawberries. Treatment time for 300 s resulted in reduction of E. coli,
      Salmonella and L. monocytogenes populations by 3.5, 3.8 and 4.2 log10 CFU/sample,
      respectively, and also effectively reduced the background microflora of tomatoes.

PMID- 24929724
TI  - Use of acetic and citric acids to control Salmonella Typhimurium in tahini
      (sesame paste).
AB  - Since tahini and its products have been linked to Salmonella illness outbreaks
      and product recalls in recent years, this study assessed the ability of
      Salmonella Typhimurium to survive or grow in commercial tahini and when hydrated
      (10% w/v in water), treated with 0.1%-0.5% acetic or citric acids, and stored at
      37, 21 and 10  degrees C for 28 d. S. Typhimurium survived in commercial tahini
      up to 28 d but was reduced in numbers from 1.7 to 3.3 log10 CFU/ml. However, in
      the moist or hydrated tahini, significant growth of S. Typhimurium occurred at
      the tested temperatures. Acetic and citric acids at <=0.5% reduced S. Typhimurium
      by 2.7-4.8 log10 CFU/ml and 2.5-3.8 log10 CFU/ml, respectively, in commercial
      tahini at 28 d. In hydrated tahini the organic acids were more effective. S.
      Typhimurium cells were not detected in the presence of 0.5% acetic acid after 7 d
      or with 0.5% citric acid after 21 d at the tested temperatures. The ability of S.
      Typhimurium to grow or survive in commercial tahini and products containing
      hydrated tahini may contribute to salmonellosis outbreaks; however, use of acetic
      and citric acids in ready-to-eat foods prepared from tahini can significantly
      minimize the risk associated with this pathogen. 

PMID- 24929726
TI  - Impact of microbial cultures on proteolysis and release of bioactive peptides in
      fermented milk.
AB  - This study aimed at evaluating co-cultures of selected microorganisms for their
      proteolytic activity and capability to produce fermented milk enriched with ACE
      inhibitory (ACEI) peptides. Selected yeasts (Torulaspora delbruekii KL66A,
      Galactomyces geotrichum KL20B, Pichia kudriavzevii KL84A and Kluyveromyces
      marxianus KL26A) and lactic acid bacteria strains (Lactobacillus plantarum LAT03,
      Lb. plantarum KLAT01 and the not virulent Enterococcus faecalis KE06) were
      screened as single cultures for their capacity of releasing ACEI peptides without
      producing bitter taste. Three strains cultures (yeast, Lb. plantarum and E.
      faecalis) were performed to evaluate the combined impact on microbial growth,
      lactic acid production, citric acid consumption, proteolysis, ACEI activity, and
      bitter taste after 36 h of fermentation at 28  degrees C. While G. geotrichum
      KL20B showed a strong stimulating effect on Lb. plantarum strains and the
      production of peptides with ACEI activity, the presence of T. delbruekii KL26A in
      the cultures was deleterious both to ACEI activity and product taste. The most
      effective combination was P. kudriavzevii KL84A, Lb. plantarum LAT3, E. faecalis
      KL06, which showed the highest ACEI activity (IC50 = 30.63 +/- 1.11 MUg ml(-1))
      and gave no bitter taste for 7 days at 6  degrees C. Our results highlight the
      importance of choosing the strains combination carefully, to obtain a high yield
      of ACEI activity without bitter taste. 

PMID- 24929727
TI  - Absence of oxygen affects the capacity to sporulate and the spore properties of
      Bacillus cereus.
AB  - This study was performed to evaluate the effect of anaerobiosis on the formation
      of Bacillus cereus spores and their resulting properties. For this purpose, an
      appropriate sporulation medium was developed (MODs). Sporulation of 18 strains
      from different phylogenetic groups of B. cereus was studied in MODs medium in
      aerobiosis and anaerobiosis. In anaerobiosis, sporulation ability was weaker and
      more heterogeneous than in aerobiosis. Among tested strains, B. cereus AH187
      produced the highest level of spores in anaerobiosis. This strain was therefore
      chosen to study spore properties. Spores produced in anaerobiosis were more
      resistant to wet heat at 90  degrees C, 92.5  degrees C, 95  degrees C, 97.5 
      degrees C and 100  degrees C. For example, D90 were 21,09 +/- 1.70 and 81.87 +/-
      2.00 for aerobiosis and anaerobiosis conditions, respectively. Spores produced in
      anaerobiosis have a z-value of 7.70  degrees C compared with 10.52  degrees C for
      spores produced in aerobiosis. Spores produced in anaerobiosis were also more
      resistant to 1 M NaOH, 1 M nitrous acid and pulsed light at fluences of 0.34 J
      cm(-2) and 0.49 J cm(-2). No difference in resistance to UV-C, 5% hydrogen
      peroxide or 0.25 mM formaldehyde was observed between these two conditions. In
      the presence of L-alanine, spores produced in anaerobiosis germinated more
      efficiently than spore produced in aerobiosis. No difference in germination was
      observed with inosine as inducer. No difference in the size of spores produced in
      the different conditions was observed by transmission electron microscopy.
      However, spores obtained under anaerobic conditions had a damaged exosporium, or
      in some cases a completely detached exosporium, unlike spores produced under
      aerobic conditions. This study shows that few spores are formed under anaerobic
      condition; nevertheless, this condition has an impact on the spore properties of
      B. cereus AH 187 strain. Spores obtained under anaerobic condition were more
      resistant to heat and to some chemical compounds. This is an important feature,
      considering the risk associated with the presence of this pathogen in thermally
      processed and packaged food in absence of oxygen.

PMID- 24929728
TI  - Enhanced tetrazolium violet reduction of Salmonella spp. by magnesium addition to
      the culture media.
AB  - Tetrazolium salts (TTZ), such as tetrazolium violet (TV), have been widely used
      for microbiological studies. The formation of the colored formazan product due to
      bacterial reduction of the uncolored reagent is extensively exploited to stain
      cells or colonies in agar or on filters. But an important toxic effect of
      tetrazolium salts on bacteria exists that limits their use at high
      concentrations, impairing the efficient staining of the colonies. This is
      especially the case for Salmonella spp. where we observed, using a classic
      photometric approach and mathematical modeling of the growth, an important impact
      of tetrazolium violet on the apparent growth rate below the inhibitory
      concentration. In this study, we demonstrate that adding magnesium to the medium
      in the presence of TV leads to a significant increase in the apparent growth
      rate. Moreover, when higher TV concentrations are used which lead to total
      inhibition of Salmonella strains, magnesium addition to the culture media allows
      growth and TV reduction. This effect of magnesium may allow the use of higher TTZ
      concentrations in liquid growth media and enhance bacteria detection
      capabilities. 

PMID- 24929729
TI  - Role of the BaeSR two-component regulatory system in resistance of Escherichia
      coli O157:H7 to allyl isothiocyanate.
AB  - Allyl isothiocyanate (AITC) is an essential oil with antimicrobial activity
      against Escherichia coli O157:H7. The ability of E. coli O157:H7 to withstand
      inhibitory AITC concentrations and the role of the two-component BaeSR system as
      a defense mechanism against AITC was studied. Optimal conditions for AITC
      stability in an aqueous medium were 25  degrees C and pH 5. The minimum
      inhibitory (MIC) and minimum bactericidal (MBC) concentrations of AITC against
      wild-type E. coli O157:H7 were 51 and 412 ppm, respectively. After growing E.
      coli O157:H7 in stepwise increased concentrations of AITC, the strain withstood
      concentrations beyond its MIC (206 ppm), but resistance was reversed when AITC
      exposure was interrupted. Deletion of either the sensor or regulator genes, baeS
      or baeR, yielded cells only as resistant as the wild-type, but the complete
      deletion of the BaeSR system decreased AITC resistance of E. coli O157:H7 to half
      that of wild-type cells. This is the first demonstration that the ability of E.
      coli O157:H7 to withstand AITC challenge is compromised by the deletion of the
      BaeSR system. It also indicates that temporary adaptive bacterial resistance to
      repeated incremental AITC exposure may occur, but it is unlikely to restrict the
      importance of AITC as an antimicrobial against E. coli O157:H7. 

PMID- 24929730
TI  - Bio-molecular characterisation of indigenous Oenococcus oeni strains from
      Negroamaro wine.
AB  - The variation in the coding capacity within Oenococcus oeni can have a
      significant impact on wine quality. The detection of several genes involved in
      important metabolic pathways (i.e. citrate, sulphur and arginine metabolisms) was
      performed on 10 indigenous O. oeni strains from Negroamaro wine, a red table wine
      (Apulia, Italy). These strains were selected from 95 isolates, collected during
      spontaneous malolactic fermentation, according to the results of an Amplified
      Fragment Length Polymorphism (AFLP) analysis. A total of 16 genes were screened,
      most (11) of which had never previously been assayed on O. oeni. All strains
      possessed 10 genes encoding enzymes such as malolactic enzyme (mleA), esterase
      (estA), citrate lyase (citD, citE and citF), citrate transporter (maeP), alpha
      acetolactate decarboxylase (alsD), alpha- acetolactate synthase (alsS), S
      adenosylmethionine synthase (metK) and cystathionine beta-lyase (metC) and
      resulted negative in the detection of genes encoding cystathionine gamma-lyase
      (metB), ornithine transcarbamylase (arcB) and carbamate kinase (arcC). The
      sequence of PCR fragments of 11 genes of a representative strain (ITEM 15929) was
      compared to those of three reference O. oeni strains. The indigenous strain was
      phylogenetically more similar to PSU-1 and ATCC BAA1163 than AWRI B429. This
      study describes new genetic markers useful for detecting the genetic potential of
      O. oeni strains to contribute to aroma production and for investigating the
      population structure of the species. 

PMID- 24929731
TI  - Lag time for germination of Penicillium chrysogenum conidia is induced by
      temperature shifts.
AB  - In the environment, fungal conidia are subject to transient conditions. In
      particular, temperature is varying according to day/night periods. All predictive
      models for germination assume that fungal spores can adapt instantaneously to
      changes of temperature. The only study that supports this assumption (Gougouli
      and Koutsoumanis, 2012, Modelling germination of fungal spores at constant and
      fluctuating temperature conditions. International Journal of Food Microbiology,
      152: 153-161) was carried out on Penicillium expansum and Aspergillus niger
      conidia that, in most cases, already produced germ tubes. In contrast, the
      present study focuses on temperature shifts applied during the first stages of
      germination (i.e., before the apparition of the germ tubes). Firstly, germination
      times were determined in steady state conditions at 10, 15, 20 and 25  degrees C.
      Secondly, temperature shifts (e.g., up-shifts and down-shifts) were applied at
      1/4, 1/2, and 3/4 of germination times, with 5, 10 and 15  degrees C magnitudes.
      Experiments were carried out in triplicate on Penicillium chrysogenum conidia on
      Potato Dextrose Agar medium according to a full factorial design. Statistical
      analysis of the results clearly demonstrated that the assumption of instantaneous
      adaptation of the conidia should be rejected. Temperature shifts during
      germination led to an induced lag time or an extended germination time as
      compared to the experiments conducted ay steady state. The induced lag time was
      maximized when the amplitude of the shift was equal to 10  degrees C. Interaction
      between the instant and the direction of the shift was highlighted. A negative
      lag time was observed for a 15  degrees C down-shift applied at 1/4 of the
      germination time. This result suggested that at optimal temperature the rate of
      germination decreased with time, and that the variation of this rate with time
      depended on temperature. 

PMID- 24929732
TI  - Microbial diversity and dynamics of Spanish-style green table-olive fermentations
      in large manufacturing companies through culture-dependent techniques.
AB  - We have studied the microbiota associated to Spanish-style green olive
      fermentations, attending to its dynamics along the time. Twenty 10-tonne
      fermenters were selected from two large table-olive manufacturing companies in
      southern Spain. While culture-dependent methodology was used to isolate the
      microorganisms, molecular methods were used to identify the isolates. A total of
      1070 isolates were obtained, resulting in 929 bacterial and 141 yeast isolates.
      Thirty seven different bacterial species were isolated, belonging to 18 different
      genera, while 12 yeast species were isolated, belonging to 7 distinct genera.
      This fermentation was dominated by the species Lactobacillus pentosus, while its
      accessory microbiota was variable and depended on the fermentation stage and the
      actual fermentation yard ("patio"). It was noticeable the abundance of lactic
      acid bacteria isolates, belonging to 16 different species. Twenty bacterial
      species were isolated for the first time from Spanish-style green olive
      fermentations, while 17 had not been described before in any table olive
      preparation. The genera Brachybacterium, Paenibacillus, Sporolactobacillus,
      Paracoccus and Yersinia had not been cited before from any table olive
      preparation. Saccharomyces cerevisiae and Candida thaimueangensis appeared to
      dominate the yeast microbiota. Candida butyri/asseri and Rhodotorula mucilaginosa
      had not been described before from Spanish-style preparations, while Saturnispora
      mendoncae was isolated for the first time from any table olive preparation.
      Biodiversity was analysed through different alpha and beta indexes which showed
      the evolution of the microbiota over time. 

PMID- 24929733
TI  - Multilocus sequence typing analysis and antibiotic resistance of Clostridium
      difficile strains isolated from retail meat and humans in Belgium.
AB  - Clostridium difficile has been isolated from food animals and meat, specially
      ground pork and ground beef. The recovered isolates were closely related to C.
      difficile human strains, indicating that animals and food are possible
      transmission routes of human C. difficile infection. The main objective of this
      study was to characterize C. difficile isolates from retail meat and to compare
      with human isolates recovered from hospital patients in Belgium. Raw meat (beef
      and pork) was obtained from the retail trade. C. difficile was recovered from
      2.3% of the beef samples and from 4.7% of the pork samples. A total of 4
      different PCR-ribotypes were identified with a large percentage of types 078 and
      014. Resistance to moxifloxacin and erythromycin was detected. The multi-locus
      sequence typing (MLST) analysis showed that meat and human isolates cluster in
      the same lineage. This study reveals the presence of toxigenic C. difficile in
      retail meat in Belgium with predominance PCR-ribotypes 078 and 014, which are
      among the four most prevalent ribotypes of C. difficile isolated from humans in
      Europe. 

PMID- 24929735
TI  - Comparison of a PCR serotyping assay, Check&Trace assay for Salmonella, and
      Luminex Salmonella serotyping assay for the characterization of Salmonella
      enterica identified from fresh and naturally contaminated cilantro.
AB  - Salmonella enterica isolated from fresh cilantro samples collected through the
      USDA/AMS Microbiological Data Program (MDP) were used to compare a PCR serotyping
      assay against the Check&Trace assay and the Luminex (BioPlex) Salmonella
      serotyping assay. The study was conducted to evaluate the effectiveness of the
      three methods for serotyping Salmonella from both enrichment broth cultures and
      pure Salmonella cultures. In this investigation, Salmonella spp. serotyping was
      conducted using 24 h enrichment broth cultures and pure Salmonella cultures from
      cilantro samples, with the PCR serotyping assay. Conversely, the Check&Trace and
      Luminex for Salmonella assays required pure cultures for Salmonella serotyping.
      The cilantro samples contained S. enterica serovar Montevideo, Newport,
      Saintpaul, and Tennessee, identified by the PCR serotyping assay and Check&Trace
      for Salmonella, but the Luminex assay only identified two of the four serotypes
      of the cilantro samples. The anticipated impact from this study is that the PCR
      serotyping assay provides a time- and cost-effective means for screening,
      identifying and serotyping Salmonella using DNA extracted from 24 h enrichment
      cilantro samples. 

PMID- 24929734
TI  - Glutamine, glutamate, and arginine-based acid resistance in Lactobacillus
      reuteri.
AB  - This study aimed to determine whether glutamine deamidation improves acid
      resistance of Lactobacillus reuteri, and to assess whether arginine, glutamine,
      and glutamate-mediated acid resistance are redundant or complementary mechanisms
      of acid resistance. Three putative glutaminase genes, gls1, gls2, and gls3, were
      identified in L. reuteri 100-23. All three genes were expressed during growth in
      mMRS and wheat sourdough. L. reuteri consistently over-expressed gls3 and the
      glutamate decarboxylase gadB. L. reuteri 100-23DeltagadB over-expressed gls3 and
      the arginine deiminase gene adi. Analysis of the survival of L. reuteri in acidic
      conditions revealed that arginine conversion is effective at pH of 3.5 while
      glutamine or glutamate conversion were effective at pH of 2.5. Arginine
      conversion increased the pHin but not DeltaPsi; glutamate decarboxylation had
      only a minor effect on the pHin but increased the DeltaPsi. This study
      demonstrates that glutamine deamidation increases the acid resistance of L.
      reuteri independent of glutamate decarboxylase activity. Arginine and
      glutamine/glutamate conversions confer resistance to lactate at pH of 3.5 and
      phosphate at pH of 2.5, respectively. Knowledge of L. reuteri's acid resistance
      improves the understanding of the adaptation of L. reuteri to intestinal
      ecosystems, and facilitates the selection of probiotic and starter cultures. 

PMID- 24929736
TI  - Development of microsatellite markers for the rapid and reliable genotyping of
      Brettanomyces bruxellensis at strain level.
AB  - Although many yeasts are useful for food production and beverage, some species
      may cause spoilage with important economic loss. This is the case of
      Dekkera/Brettanomyces bruxellensis, a contaminant species that is mainly
      associated with fermented beverages (wine, beer, cider and traditional drinks).
      To better control Brettanomyces spoilage, rapid and reliable genotyping methods
      are necessary to determine the origins of the spoilage, to assess the
      effectiveness of preventive treatments and to develop new control strategies.
      Despite several previously published typing methods, ranging from classical
      molecular methods (RAPD, AFLP, REA-PFGE, mtDNA restriction analysis) to more
      engineered technologies (infrared spectroscopy), there is still a lack of a
      rapid, reliable and universal genotyping approach. In this work, we developed
      eight polymorphic microsatellites markers for the Brettanomyces/Dekkera
      bruxellensis species. Microsatellite typing was applied to the genetic analysis
      of wine and beer isolates from Europe, Australia and South Africa. Our results
      suggest that B. bruxellensis is a highly disseminated species, with some strains
      isolated from different continents being closely related at the genetic level. We
      also focused on strains isolated from two Bordeaux wineries on different
      substrates (grapes, red wines) and for different vintages (over half a century).
      We showed that all B. bruxellensis strains within a cellar are strongly related
      at the genetic level, suggesting that one clonal population may cause spoilage
      over decades. The microsatellite tool now paves the way for future population
      genetics research of the B. bruxellensis species. 

PMID- 24929737
TI  - Use of propidium monoazide for the enumeration of viable Brettanomyces
      bruxellensis in wine and beer by quantitative PCR.
AB  - Brettanomyces bruxellensis is a current problem in winemaking all over the world,
      and the question if B. bruxellensis has a positive or negative impact on wine is
      one of the most controversial discussions in the world. The presence of live B.
      bruxellensis cells represents the risk of growth and an increase in cell numbers,
      which is related to the potential production of volatile phenols. In this work,
      the optimisation of a PMA-quantitative PCR (qPCR) method to enumerate only viable
      cells was carried out using the standard strain B. bruxellensis DSMZ 70726. The
      obtained detection limits were 0.83 log CFU/mL in red wine, 0.63 log CFU/mL in
      white wine and 0.23 log CFU/mL in beer. Moreover, the quantification was also
      performed by Reverse Transcription quantitative PCR (RT-qPCR), and the results
      showed a higher detection limit for all of the trials. 

PMID- 24929738
TI  - Application of ISSR-PCR for rapid strain typing of Debaryomyces hansenii isolated
      from dry-cured Iberian ham.
AB  - Yeast populations of dry-cured Iberian ham isolated from seven industries in the
      province of Badajoz were characterized by ISSR-PCR using the (CAG)4 primer and
      PCR-RFLP of the ITS1-5.8S rRNA-ITS2 fragment, and identified by DNA sequencing. A
      total of 242 isolates were analyzed, indicating the primary species present was
      Debaryomyces hansenii at 80.9% of the isolates followed by Candida zeylanoides at
      10.3% of the isolates. The remainders of isolates were identified as Yamadazyma
      triangularis, Sporobolomyces roseus, Meyerozyma guilliermondii, Rhodotorula
      slooffiae, and Cryptococcus victoriae. The ISSR-PCR method was a fast and
      reliable method which was able to discriminate species at a level comparable to
      restriction analyses of the ITS1-5.8S rRNA-ITS2 region. This method allowed for
      strain typing of D. hansenii, yielding 29 different PCR patterns within 196
      isolates. Moreover, ISSR-PCR using the (CAG)4 primer indicated that this
      technique could be a promising tool for rapid discrimination of yeast starter
      cultures and spoilage species in dry-cured Iberian ham. 

PMID- 24929739
TI  - A comparison of the thermal inactivation kinetics of human norovirus surrogates
      and hepatitis A virus in buffered cell culture medium.
AB  - Human noroviruses and hepatitis A virus (HAV) are considered as epidemiologically
      significant causes of foodborne disease. Therefore, studies are needed to bridge
      existing data gaps and determine appropriate parameters for thermal inactivation
      of human noroviruses and HAV. The objectives of this research were to compare the
      thermal inactivation kinetics of human norovirus surrogates (murine norovirus
      (MNV-1), and feline calicivirus (FCV-F9)) and HAV in buffered medium (2-ml
      vials), compare first-order and Weibull models to describe the data, calculate
      Arrhenius activation energy for each model, and evaluate model efficiency using
      selected statistical criteria. The D-values calculated from the first-order model
      (50-72  degrees C) ranged from 0.21-19.75 min for FCV-F9, 0.25-36.28 min for MNV
      1, and 0.88-56.22 min for HAV. Using the Weibull model, the tD = 1 (time to
      destroy 1 log) for FCV-F9, MNV-1 and HAV at the same temperatures ranged from
      0.10-13.27, 0.09-26.78, and 1.03-39.91 min, respectively. The z-values for FCV
      F9, MNV-1, and HAV were 9.66  degrees C, 9.16  degrees C, and 14.50  degrees C,
      respectively, using the Weibull model. For the first order model, z-values were
      9.36  degrees C, 9.32  degrees C, and 12.49  degrees C for FCV-F9, MNV-1, and
      HAV, respectively. For the Weibull model, estimated activation energies for FCV
      F9, MNV-1, and HAV were 225, 278, and 182 kJ/mol, respectively, while the
      calculated activation energies for the first order model were 195, 202, and 171
      kJ/mol, respectively. Knowledge of the thermal inactivation kinetics of norovirus
      surrogates and HAV will allow the development of processes that produce safer
      food products and improve consumer safety. 

PMID- 24929740
TI  - Selection of appropriate Schizosaccharomyces strains for winemaking.
AB  - This paper describes the selection of Schizosaccharomyces yeasts with adequate
      oenological suitability and high capacity for the degradation of malic acid.
      Despite the almost non-existent number of commercial strains, the use of this
      yeast genus has recently been recommended by the International Organisation of
      Vine and Wine (OIV, in French). Thus, in the present study, a large number of
      Schizosaccharomyces strains were isolated using a selective differential medium.
      Initially, classic parameters of oenological interest for the use of fermentative
      strains of Saccharomyces cerevisiae (the most frequently used type of yeast) were
      assessed. Only five strains of moderate acetic acid production lower than 0.4 g/L
      were obtained at the end of fermentation. Other, more specific features of this
      yeast genus' physiology were also studied, including urease activity and the
      production of pyruvic acid and glycerol. Finally, oenological suitability was
      determined by comparing selected strains with other Schizosaccharomyces reference
      and S cerevisiae control strains. Schizosaccharomyces strains produced 80% less
      urea content, four times higher pyruvic acid levels and 1 g higher glycerol
      contents than the Saccharomyces reference strains. The results confirmed that it
      is possible to perform selective processes on microorganisms from the genus
      Schizosaccharomyces using methodology developed in this work to obtain strains of
      industrial interest. 

PMID- 24929741
TI  - Numbers of coliforms, Escherichia coli, F-RNA phage, rotavirus, bovine enteric
      calicivirus and presence of non-O157 STEC on commercial vacuum packaged beef.
AB  - The numbers of coliforms, Escherichia coli, F-RNA coliphages, bovine enteric
      calicivirus (BEC) and rotavirus (RV) and presence of non-O157 shiga toxigenic E.
      coli (STEC) were determined on commercial vacuum packaged beef subprimals at the
      retail level from swabs obtained from the entire surfaces of 150 cuts that
      originated from federally and provincially registered plants. The prevalence and
      log mean numbers of E. coli were higher in provincially registered plants than in
      federally registered plants; 64% vs 20%, respectively, and -0.3 vs -1.22 log
      cfu/100 cm(2), respectively. In contrast, the prevalence and mean log numbers of
      F-RNA coliphages were lower for the provincially registered plants than for the
      federally registered plants; 31% vs 68% and -0.86 vs -0.13 log cfu/100 cm(2),
      respectively. One E. coli sample tested positive for stx2 and eae. F-RNA
      coliphages associated with human origin (GII/GIII) were detected in 12% and 30%
      of samples that originated from provincially and federally registered plants,
      respectively. RV RNA was detected in 4% of samples while BEC RNA was not
      detected. Although the infectivity of RV is unknown, the presence of viable F-RNA
      coliphages suggests that consumers could potentially be at risk when consuming
      undercooked meat that is contaminated with RV. 

PMID- 24929742
TI  - Horizontal gene transfer among microorganisms in food: current knowledge and
      future perspectives.
AB  - The possibility of horizontal gene transfer (HGT) among microorganisms in food
      matrices has been specifically targeted in a few investigations, though most
      current knowledge has been obtained indirectly or derived from genome sequence
      analyses. In this review, we have assembled reported examples of the HGT events
      that probably occurred in food matrices since the bacterial partners involved are
      commonly found in association in a food matrix or are specifically adapted to it.
      Exchanged genes include those encoding for substrate utilization, bacteriocin,
      exopolysaccharide and biogenic amine (BA) production, immunity to bacteriophages
      and antibiotic resistance (AR). While the acquisition of new traits involved in
      substrate utilization led to the natural genetic improvement of the microbial
      cultures for food production, the acquisition of hazardous traits, e.g., AR,
      virulence or BA production genes, can give rise to health concerns in otherwise
      innocuous species. Available evidence suggests that it would be opportune to
      determine what conditions favour HGT among bacteria in food ecosystems in order
      to naturally obtain improved starter or adjunct cultures, and also to prevent the
      propagation of hazardous traits. 

PMID- 24929743
TI  - Norcocaine in human hair as a biomarker of heavy cocaine use in a high risk
      population.
AB  - In hair analysis, cocaine (COC) and its metabolites have been studied relatively
      extensively with a consistent focus of distinguishing active drug use and
      excluding external contamination. Although quantitative cut-offs using major
      metabolite, benzolecgonine (BE), in hair have been proposed to distinguish likely
      active use from passive exposure, exogenously formed BE may result in false
      positive tests. Hence, the presence of less commonly detected COC metabolite,
      norcocaine (NCOC), may be useful in increasing certainty of illicit COC use and
      evaluating likelihood of environmental contamination. The objective of the
      present study was to observe the pattern of NCOC detection in a clinical
      population of suspected users and evaluate the possible role of NCOC in
      distinguishing systemic exposure from external contamination to COC and assessing
      intensity of cocaine use. Hair samples collected between January 2011 and May
      2013 from the Motherisk Laboratory were analyzed by GC-MS for the presence of
      COC, BE, and NCOC. NCOC positivity rates (%) for various COC concentration ranges
      as well as sensitivity, specificity, positive predictive value, and negative
      predictive values of NCOC as a biomarker of different COC use profiles was
      calculated. The rate of NCOC positivity (%) within COC concentration ranges
      (ng/mg) 0.13-0.4 (above LOD, below LOQ), 0.4-3, 3-6, 6-10, 10-14, >14 were 0.26,
      4.15, 29.63, 55.85, 80.37, and 94.02, respectively; p<0.0001 for all positivity
      comparisons between ranges. These results were used to determine a COC cut-off
      concentration for differing levels of COC use. The presence of NCOC above the LOD
      of 0.13 ng/mg predicted COC concentrations exceeding 14.00 ng/mg, with
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of 94.0%, 87.9%, 41.5%, and 99.4%, respectively. The
      presence NCOC above the LOD of 0.13 ng/mg predicted COC concentrations exceeding
      the 75th percentile, with sensitivity, specificity, PPV, and NPV of 76.6%, 94.7%,
      74.7%, and 95.2%, respectively. Despite an inability to definitively rule out
      external contamination, the presence of NCOC in hair is strongly associated with
      elevated COC levels and performs as a highly specific surrogate marker for
      frequent/intensive cocaine use and highly sensitive marker for intensive/daily
      use of cocaine.

PMID- 24929744
TI  - A positive tangent sign predicts the repairability of rotator cuff tears.
AB  - HYPOTHESIS: We hypothesize that patients with a positive tangent sign will have
      rotator cuff tears that are not able to be repaired primarily. METHODS: We
      performed a retrospective review of the charts of patients who had undergone
      surgery for repair of a rotator cuff tear. The operative note was reviewed to
      determine whether the cuff tear was primarily repaired. The magnetic resonance
      imaging study of each patient was reviewed to assess for a positive or negative
      tangent sign. The reviewer was blinded to the result of each measurement.
      RESULTS: Eighty-one patients met the inclusion criteria. Of the 79 included in
      our analyses, 17 had a positive tangent sign and 62 had a negative tangent sign.
      There was only 1 patient with a negative tangent sign who had an irreparable
      rotator cuff tear. There were 3 patients with a positive tangent sign who had a
      repairable rotator cuff. With a pretest prevalence of irreparable tears of 18.9%,
      a positive finding suggested a post-test probability of 82.3% with a positive
      tangent sign and a post-test probability of only 1.6% when the tangent sign was
      negative. CONCLUSION: Our results showed decision-making value in both a negative
      tangent sign and a positive tangent sign. The tangent sign is an easily performed
      and reproducible tool with good intraobserver and interobserver reliability that
      is a powerful predictor of whether a rotator cuff tear will be repairable.

PMID- 24929745
TI  - Patterns of proximal humeral bone resorption after total shoulder arthroplasty
      with an uncemented rectangular stem.
AB  - BACKGROUND: The aim of this study was to assess the timing and location of
      cortical bone resorption after total shoulder arthroplasty with an uncemented
      rectangular stem and investigate its effect on shoulder function up to 5 years
      after implantation. METHODS: Between June 2003 and September 2006, 183
      consecutive total shoulder arthroplasties were performed, 133 of which received a
      cementless rectangular stem as indicated by primary or post-traumatic
      osteoarthritis (OA). The 5-year postoperative follow-up rate was 80%.
      Standardized radiographic controls and clinical assessments were performed at 6
      weeks, 6 months, and 1, 2, and 5 years. RESULTS: Twenty-two patients (17%) showed
      full-thickness cortical bone resorption, 21 of whom were diagnosed with Sperling
      zone 2 resorption. The maximum craniocaudal distance of full resorption averaged
      19.1 mm (range, 5.6-46.7 mm). The median distance progressed significantly from
      9.6 mm to 13.8 mm between 6 and 12 months (P = .005). The risk of bone resorption
      was 3.1 times higher for post-traumatic OA patients than for those with primary
      OA. The occurrence of bone resorption increased significantly with increasing
      stem diameters relative to the humeral diameter. There was no significant effect
      of bone resorption on functional outcome. CONCLUSION: Full-thickness cortical
      bone resorption in the proximal posterolateral humerus after receipt of a
      cementless rectangular stem has a prevalence of 17%, mostly occurring within the
      first year after surgery. Risk factors include age, post-traumatic conditions,
      and larger stem sizes relative to the humerus. This is a radiographic phenomenon
      without significant impairment of function or need for revision within 5 years
      after surgery.

PMID- 24929747
TI  - Rapid tracheal deviation and airway compromise due to fluid extravasation during
      shoulder arthroscopy.

PMID- 24929746
TI  - Reverse shoulder arthroplasty as salvage for failed prior arthroplasty in
      patients 65 years of age or younger.
AB  - BACKGROUND: This study examined outcomes and complications in young patients
      undergoing revision reverse total shoulder arthroplasty (RTSA) for failed prior
      total shoulder arthroplasty or hemiarthroplasty and compared them with those of
      an age-matched cohort undergoing primary RTSA. METHODS: RTSA as a revision for
      failed shoulder arthroplasty was performed on 36 patients younger than 65 years.
      Follow-up was available for 32 patients at an average of 55.3 months. Results
      were compared with those of an age-matched cohort of 37 patients (33 available
      for follow-up; average, 54.7 months) undergoing primary RTSA. Average age for
      both groups was 59.3 years. Outcomes were compared before and after revision
      surgery and between cohorts. RESULTS: Preoperative visual analog scale (VAS) for
      pain and subjective shoulder value (SSV) scores were similar in both groups, 7.3
      of 10 and 24%, respectively, before revision, and 7.0 of 10 and 19% before
      primary RTSA (P = .3). Postrevision VAS and SSV scores improved to 1.4 of 10 and
      60% (P < .0001). Average American Shoulder and Elbow Surgeons and Simple Shoulder
      Test scores after revision were 69.7 and 58.8, with 9 complications (28.1%; 6
      major and 3 minor). VAS and SSV scores improved to 2.1 of 10 and 76% after
      primary RTSA (P < .0001). American Shoulder and Elbow Surgeons and Simple
      Shoulder Test scores after primary RTSA were 74 and 67.3, with 6 complications
      (18.2%; 5 major and 1 minor). Only the postoperative SSV score was statistically
      different in comparing primary and revision RTSA (P < .05). CONCLUSION: RTSA is
      effective in reducing pain and improving function after failed arthroplasty in
      young patients, but complication rates are high and expectations should be
      managed appropriately. Subjective outcome scores are worse than those for age
      matched patients undergoing primary RTSA, but pain, functional scores, and
      complication rates are similar.

PMID- 24929748
TI  - Glenohumeral instability and coracoid fracture nonunion corrected without
      coracoid transfer or nonunion takedown.

PMID- 24929749
TI  - Clavicle stress fracture after reverse shoulder arthroplasty.

PMID- 24929750
TI  - Seroepidemiology and phylogenetic characterisation of measles virus in Ireland,
      2004-2013.
AB  - BACKGROUND: Ireland is classified as an area of high measles incidence. A World
      Health Organisation-European Region strategic plan exists for measles elimination
      by 2015. OBJECTIVES: To retrospectively investigate measles outbreaks using all
      patient samples (sera and oral fluid) received for measles laboratory diagnosis
      and characterise the genetic diversity of circulating measles genotypes in
      Ireland. STUDY DESIGN: 704 cases of acute measles infection as determined by the
      presence of measles specific IgM in sera and oral fluids were confirmed at the
      National Virus Reference Laboratory. Measles positive samples (n=116) were
      examined by genotyping, sequence analysis and phylogenetic characterisation.
      RESULTS: Three measles outbreaks occurred over the study period: 2004, 2009/2010
      and 2011. Measles IgM positivity ranged from 22-29% in outbreak years to 5-10% in
      the intervening years. Age profile analysis revealed that whereas individuals >10
      years accounted for only 8% of cases in the 2004 outbreak, this increased to 33%
      and 29% in the 2009/2010 and 2011 outbreaks, respectively. The <1 year cohort
      accounted for 18-20% of cases in all outbreaks. Phylogenetic analysis
      demonstrated both indigenous transmission and also importation events. Clade D
      viruses were exclusively found circulating in Ireland, with autochthonous
      transmission of diverse genotype D4 strains associated with large outbreaks
      across Europe. More recently, genotype D8 was identified and these were
      associated with importation events. CONCLUSIONS: This study provides a
      comprehensive genetic analysis of circulating measles genotypes in Ireland and
      discriminated between indigenous and imported viral strains. Notably, an increase
      in laboratory-confirmed measles cases in the greater than 10 years of age group
      was seen over the study period. This information is valuable to inform
      vaccination strategies with a focus on those populations who remain susceptible
      to measles infection.

PMID- 24929751
TI  - Telaprevir pharmacokinetics in a hepatitis C virus infected patient on
      haemodialysis.

PMID- 24929753
TI  - Progressive multifocal leukoencephalopathy complicating untreated chronic
      lymphatic leukemia: case report and review of the literature.
AB  - A 58-year old female with a four-year history of previously untreated CLL at
      Binet stage A complained about word finding problems, impaired vision, and gait
      unsteadiness. Concerning her CLL she was asymptomatic and had never required any
      specific treatment. Her neurological examination disclosed cognitive alterations,
      homonyme hemianopia to the right, aphasia, and mild right-sided hemiparesis.
      Cerebral MRI showed a hyperintense lesion on T2 weighted images without contrast
      enhancement. CSF examination revealed normal findings, including CSF protein,
      cell count, cytology and PCR-analysis was negative for the presence of JC virus
      DNA. On follow-up MRI, performed 2 weeks later, the T2 lesion was further
      enlarging. Subsequent stereotactic brain biopsy was diagnostic for PML revealing
      abnormal oligodendrocytes staining positive against antibodies specific for
      simian vacuolating virus 40. In addition, repeated CSF analyses for JC-Virus DNA
      in the course of the disease became positive. After confirmation of diagnosis
      treatment with mirtazapine (30 mg/d) and mefloquine (250 mg/d) was initiated.
      Rapid clinical progression correlated to further worsening on MRI. Therefore this
      treatment was terminated after 16 days and the regime was changed to a five-day
      courses of cytarabine (2 mg/kg/d) combined with intrathecal administration of
      liposomal cytarabine (50 mg). Due to further clinical progression with global
      aphasia, blindness and severe right-sided hemiparesia, medication was stopped.
      The Patient died three and a half months after onset of symptoms.

PMID- 24929752
TI  - Comparison of the Gen-Probe Aptima HIV-1 and Abbott HIV-1 qualitative assays with
      the Roche Amplicor HIV-1 DNA assay for early infant diagnosis using dried blood
      spots.
AB  - BACKGROUND: The current gold standard for infant diagnosis of HIV-1 is the Roche
      Amplicor Qualitative DNA assay, but it is being phased out. OBJECTIVE: Compare
      the Abbott qualitative assay and the Gen-Probe Aptima assay to the gold standard
      Roche DNA assay using dried blood spots (DBS). STUDY DESIGN: The Gen-Probe Aptima
      and Abbott qualitative HIV-1 assays were compared to the Roche DNA assay for
      early infant diagnosis. Specificity and sensitivity were determined for the three
      assays using DBS from 50 HIV-exposed uninfected infants and 269 HIV-1 infected
      adults from North Carolina, respectively. All of the negative and 151 of the
      positive DBS had valid results on the 3 different assays, and an additional 118
      positive DBS had valid results on the Roche DNA and Aptima assays. RESULTS: All
      three assays were very specific. The Roche DNA assay was the most sensitive
      (96.7%) over a wide range of HIV PVL, including samples with PVL<400 copies/ml.
      Restricted to samples with PVL>400 copies/ml, the Gen-Probe Aptima assay had
      sensitivity (96.5%) comparable to the Roche DNA assay (98.8%). The Abbott
      Qualitative assay was the least sensitive and only had sensitivity above 95%
      among samples with PVL over 1000 copies/ml. CONCLUSIONS: The Abbott HIV-1
      Qualitative assay was not as sensitive as the comparator assays, so it would not
      be a useful replacement assay, especially for infants taking antiretroviral
      prophylaxis. The Gen-Probe Aptima assay is an adequate replacement option for
      infant diagnosis using DBS.

PMID- 24929754
TI  - A qualitative PCR minipool strategy to screen for virologic failure and
      antiretroviral drug resistance in South African patients on first-line
      antiretroviral therapy.
AB  - BACKGROUND: The high cost of commercial HIV-1 viral load tests for monitoring of
      patients on antiretroviral treatment limits their use in resource-constrained
      settings. Commercial genotypic antiretroviral resistance testing is even more
      costly, yet it provides important benefits. OBJECTIVES: We sought to determine
      the sensitivity and negative predictive value of a qualitative PCR targeting
      partial reverse transcriptase for detection of virologic failure when 5 patient
      specimens are pooled. STUDY DESIGN: A total of 300 South African routine patient
      samples were included and tested in 60 pools of 5 samples each. A qualitative
      nested PCR was optimised for testing pools and individual samples from positive
      pools. All positive samples were sequenced to detect drug resistance-associated
      mutations. Results were compared to those of conventional viral load monitoring.
      RESULTS: Twenty-two of 60 pools tested positive. Individual testing yielded 29
      positive individual samples. Twenty-six patients had viral loads of above 1000
      copies/ml. The pooling algorithm detected 24 of those 26 patients, resulting in a
      negative predictive value of 99.3%, and a positive predictive value of 89.7%. The
      sensitivity for detecting patients failing therapy was 92%, with a specificity of
      98.9%. Of the patients failing first-line ART, 83.3% had NRTI and 91.7% NNRTI
      resistance mutations. CONCLUSIONS: The pooled testing algorithm presented here
      required 43% fewer assays than conventional viral load testing. In addition to
      offering a potential cost saving over individual viral load testing, it also
      provided drug resistance information which is not available routinely in
      resourced-limited settings.

PMID- 24929755
TI  - Hepatitis E prevalence among HIV infected patients with elevated liver enzymes in
      the Netherlands.
AB  - BACKGROUND: In recent years chronic hepatitis E virus (HEV) infections have been
      reported in immunosuppressed patients, including HIV-positive patients with low
      CD4 cell counts. Because of delayed anti-HEV seroconversion in patients with CD4
      cell count<200 cells/ml it is difficult to draw firm conclusions on HEV
      seroprevalence in a population of HIV positive patients. OBJECTIVES: To determine
      the HEV seroprevalence in a population of HIV infected patients. STUDY DESIGN: We
      retrospectively analysed the HEV prevalence in a population of 256 HIV infected
      patients with liver enzyme elevations (LEEs), using HEV specific antibody testing
      and HEV-RNA detection. RESULTS: Within this cohort we observed a HEV
      seroprevalence of 11.7%, without any anti-HEV IgM positive or HEV-RNA positive
      cases. HEV seropositivity was equally prevalent among different CD4(+) cell count
      groups. CONCLUSION: Although HIV infected patients in the Netherlands are at risk
      of acquiring HEV, the number of acute infections is low and no chronic cases were
      found.

PMID- 24929757
TI  - Big ideas: A grief observed.

PMID- 24929756
TI  - Microwave assisted synthesis, characterization and biocidal activities of some
      new chelates of carbazole derived Schiff bases of cadmium and tin metals.
AB  - This study is planned to report the advancement of green microwave approach in
      the fabrication of a new series of biologically potent (N^X, where X=O/S) donor
      Schiff bases and their cadmium(II) and tin(II) complexes. The ligands and their
      metal complexes have been characterized in terms of elemental analysis, molar
      ionic conductance, magnetic moment and spectral (IR, UV-Vis, NMR ((1)H, (119)Sn),
      FAB-mass, thermal and XRD) data. The data revealed that the ligands coordinated
      to the metal center via nitrogen and oxygen/sulfur atoms and form an octahedral
      arrangement of the ligands around central metal atom. All compounds were
      evaluated for their in vitro antimicrobial activities against two pathogenic
      bacteria Bacillus subtilis and Escherichia coli and two fungi Aspergillus niger
      and Aspergillus flavus by standard disc diffusion method. The discs were stored
      in an incubator at 37 degrees C. The compounds were dissolved in DMF at 500 and
      1000 ppm concentrations for screening biocidal activity. The compounds were
      dissolved in DMF to get the 100 and 200 ppm concentration of test solutions for
      screening fungicidal activity. The inhibition zone around each disc was measured
      (in mm) after 24 h and 96 h for biocidal and fungicidal activities respectively.

PMID- 24929758
TI  - Vagus-preserving technique during minimally invasive esophagectomy: the effects
      on cardiac parameters in a swine model.
AB  - BACKGROUND: Cardiac complications are an important cause of morbidity and
      mortality observed after esophageal resections. We examined whether an high
      intrathoracic vagotomy during abdominothoracic esophagectomy would have an effect
      on intraoperative and early postoperative cardiac function in the setting of a
      minimally invasive resection. Two hypotheses were generated for this study: (1)
      Vagotomy would cause cardiac changes, and (2) vagus-preserving esophagectomy
      would prevent cardiac problems during resection and in the early postoperative
      phase. METHODS AND RESULTS: Thirty male pigs were operated on while cardiac
      parameters (heart rate [HR], cardiac index [CI], preload recruitable stroke work
      [PRSW], contractility speed [dp/dtmax], relaxation speed [dp/dtmin], and
      relaxation time [tau]) were monitored using a conductance catheter and the
      thermodilution method. Animals were randomized into 4 groups (each n = 7): (1)
      control, thoracoscopy only, (2) thoracoscopy with vagotomy, (3) esophageal
      resection with vagotomy, and (4) esophageal resection with vagus nerve
      preservation. To evaluate the first hypothesis, we compared groups 1 and 2; to
      evaluate the second hypothesis, we compared groups 3 and 4. HR, CI, PRSW,
      dp/dtmax, and tau were different in the 2 groups without resection (area under
      the curve; each P < .05). Vagotomy with esophagectomy resulted in nonsignificant
      differences between groups 3 and 4. The requirement for metoprolol administration
      to avoid severe tachycardia was greater in the groups that underwent vagotomy (P
      < .05; Fisher's exact test). CONCLUSION: An high intrathoracic vagotomy results
      in loss of vagal tone and a greater rate of tachycardia during thoracoscopy and
      esophagectomy. There were no differences, however, in cardiac dynamics between
      the esophagectomy groups. Thus, vagal injury is not the sole reason for cardiac
      dysfunction after esophagectomy.

PMID- 24929759
TI  - Comparison of the staging of regional lymph nodes using the sixth and seventh
      editions of the tumor-node-metastasis (TNM) classification system for the
      evaluation of overall survival in gastric cancer patients: findings of a case
      control analysis involving a single institution in China.
AB  - BACKGROUND: It has recently been reported that the sixth edition of the tumor
      node-metastasis (TNM) classification system for gastric cancer involving the
      staging of regional lymph nodes (N) has inappropriate cut-offs with regard to
      counts of metastatic lymph nodes. It remains controversial, however, as to
      whether the seventh edition of this classification system is completely accurate
      in staging N for the prediction of the prognosis of gastric cancer. Our aim was
      to determine which of these two editions of the TNM classification system was
      superior with regard to the prediction of the prognosis of Chinese patients with
      gastric cancer. METHODS: We analyzed relevant clinicopathological data
      statistically from 1,563 patients with gastric cancer who had undergone curative
      resection to evaluate the sixth and seventh editions of the TNM classification
      system for N staging with regard to the prediction of overall survival (OS).
      RESULTS: Our survival analyses demonstrated that N staging via use of both the
      sixth and seventh editions of the TNM classification system was correlated with
      OS. Furthermore, case-control analysis indicated that the seventh edition was
      significantly superior to the sixth edition in predicting the OS of patients,
      regardless of the extent of lymphadenectomy (D1 or D2) and the number of
      dissected lymph nodes (<16 or >=16). By taking into consideration both the extent
      of lymphadenectomy and the number of dissected lymph nodes simultaneously, we
      determined that the seventh edition of the TNM classification system was superior
      to the sixth edition regarding the evaluation of the OS in the various subgroups
      of gastric cancer patients. CONCLUSION: The seventh edition proved more reliable
      and accurate than the sixth edition of the TNM classification system in
      categorizing the number of metastatic lymph nodes for the purpose of predicting
      the OS of patients with gastric cancer after curative resection.

PMID- 24929760
TI  - Leakage of the gastroenteric anastomosis after pancreatoduodenectomy.
AB  - BACKGROUND: Common anastomotic complications after pancreatoduodenectomy (PD) are
      leakage from the pancreaticojejunostomy or hepaticojejunostomy. Leakage from the
      gastroenteric anastomosis has rarely been described. We evaluated the incidence
      of gastroenteric leakage after PD and described its presentation, treatment, and
      outcome. METHODS: Between 1992 and 2012, a consecutive series of 1,036 patients
      underwent PD in the Academic Medical Center. By use of a prospective database and
      medical records, we identified patients with gastroenteric leakage.
      Clinicopathologic data were compared with patients without gastroenteric leakage,
      and presentation, radiologic findings, treatment, and outcome of gastroenteric
      leaks were analyzed. RESULTS: Twelve patients (1.2%) had gastroenteric leakage.
      Patients with gastroenteric leaks had undergone longer operative procedures, had
      more pancreatic fistulas and other complications, and had a significantly longer
      hospital stay. Median postoperative day of diagnosis was 8 (range, 2-23).
      Clinical signs included tender abdomen and high drain output suspicious of
      gastric content. Common radiologic findings were pneumoperitoneum and intra
      abdominal fluid. Seven patients (58%) were treated operatively, 4 (33%) by
      percutaneous drainage, and 1 (8%) underwent no specific treatment duo to his poor
      clinical condition. This patient died in hospital, resulting in a hospital
      mortality of 8%. CONCLUSION: Gastroenteric leakage after PD is rare. Clinical
      presentation is not specific, unlike leakage from other sites. Drain output
      suspicious of gastric content may help to differentiate from pancreatic or
      hepatic anastomotic leakage. It may be associated with a longer duration of
      operation and concomitant pancreatic fistula. A good outcome depends on prompt
      diagnosis and is mostly achieved by operative intervention.

PMID- 24929762
TI  - Hepatic steatosis is associated with surgical-site infection after hepatic and
      colorectal surgery.
AB  - BACKGROUND: Obesity and increased visceral fat deposits are important risk
      factors for surgical-site infection (SSI). Interestingly, a potential role of
      hepatic steatosis on complications after extrahepatic surgery remains unknown.
      The aim of the present study was to investigate the impact of hepatic steatosis
      on SSI in patients that underwent open abdominal surgery. METHODS: A total of 231
      patients that underwent either liver (n = 116) or colorectal (n = 115) resection
      and received preoperative contrast-enhanced computed tomography scans were
      retrospectively investigated. Signal attenuation of the liver parenchyma was
      measured on computed tomography scans to assess hepatic steatosis. RESULTS: More
      SSIs (including types 1, 2, and 3) were found in the group with hepatic steatosis
      (56/118 [47.5%]) compared with the control group (30/113 [26.6%]; P = .001).
      Patients with hepatic steatosis showed greater median body mass index than
      patients without hepatic steatosis (26.6 kg/m(2) [range 16.8-47.0 kg/m(2)] vs
      23.2 kg/m(2) [15.9-32.7 kg/m(2)]; P < .001). Patients with hepatic steatosis
      experienced longer median operation times (297 minutes [52-708 minutes] vs 240
      minutes [80-600 minutes]; P = .003). In a multivariate analysis, hepatic
      steatosis was identified as an independent risk factor for SSI in patients
      undergoing hepatic (odds ratio 10.33 [95% confidence interval 1.19-89.76]; P =
      .03) or colorectal (odds ratio 6.67 [95% confidence interval 1.12-39.33]; P =
      .04) operation. CONCLUSION: Hepatic steatosis is associated with SSI after
      hepatic and colorectal operation.

PMID- 24929761
TI  - Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression
      in cancer cells and cancer-associated fibroblasts in pancreatic head cancer.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an
      aggressive biology and poor prognosis. Experimental evidence has suggested a role
      for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in
      epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1
      expression has been observed in cancer cells as well as stromal fibroblasts. Our
      study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue.
      METHODS: Patient baseline and follow-up data were extracted from a prospectively
      maintained database. After clinicopathologic re-review, serial sliced tissue
      slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin.
      ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded
      separately and correlated to routine histopathologic parameters and survival
      after resection. RESULTS: A total of 117 cases of PDAC were included in the
      study. High ZEB1 expression in cancer cells and in stromal cancer-associated
      fibroblasts was associated with poor prognosis. There was also a trend for poor
      prognosis with a lymph node ratio of greater than 0.10. In line with its role as
      an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells
      was positively correlated with Vimentin expression and negatively with E-Cadherin
      expression. In multivariate analysis, stromal ZEB1 expression grade was the only
      independent factor of survival after resection. CONCLUSION: Our data suggest that
      ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong
      prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first
      time as an independent predictor of survival after resection of PDAC. This
      observation suggests that therapies targeting ZEB1 and its downstream pathways
      could hit both cancer cells and supporting cancer-associated fibroblasts.

PMID- 24929763
TI  - Predicting hypocalcemia after thyroidectomy in children.
AB  - BACKGROUND AND AIMS: Hypocalcemia after thyroidectomy is caused by parathyroid
      trauma. There are no studies regarding the usefulness of intact parathyroid
      hormone (PTH) as a monitor of postoperative hypoparathyroidism tool in
      pediatrics. We evaluated the diagnostic accuracy of intra- and postoperative PTH
      to predict the risk of developing post thyroidectomy hypocalcemia in children.
      METHODS: A prospective longitudinal cohort study was conducted in 32 pediatric
      patients (3.2-17.6 years old) undergoing total thyroidectomy. Intact PTH measured
      by the assays (Immulite Immunoassay System [ICMA] or electrochemioluminescence
      assay [ECLIA]) at 5 (PTH-5) and 60 (PTH-60) minutes after thyroid removal were
      considered as predicting variables. The postoperative outcome was hypocalcemia
      (endpoint variable). Patients were clinically and biochemically monitored
      regularly for 48 hours after surgery. RESULTS: Of the patients, 47% developed
      hypocalcemia (15% symptomatic). An ICMA PTH-5 of <=14 pg/mL or an ECLIA PTH-5 of
      <=16 pg/mL predicted hypocalcemia with a sensitivity of 80%, specificity of 100%,
      positive predictive value (PPV) of 100%, and diagnostic efficiency (DE) of 91%.
      Using the same cutoff values, PTH-60 presented a sensitivity of 93%, specificity
      of 82%, PPV of 81%, and DE of 87%. Adjusting for variation in the assays and
      combining intra- and postoperative PTH determinations, we developed an algorithm
      that improved sensitivity, specificity, and DE. CONCLUSION: PTH is useful for
      predicting hypocalcemia after total thyroidectomy in children. The use of our
      proposed strategy should be considered to (a) initiate preventive treatment in
      patients identified at high risk for hypocalcemia, (b) shorten the duration of
      hospitalization, and (c) reduce the clinical and biochemical controls in those
      who remained normocalcemic.

PMID- 24929764
TI  - Radio-guided selective compartment neck dissection improves staging in papillary
      thyroid carcinoma: a prospective study on 345 patients with a 3-year follow-up.
AB  - BACKGROUND: Prospective uncontrolled study to investigate in papillary thyroid
      carcinoma (PTC) patients: (1) Distribution of lymph node metastases within the
      neck compartments, (2) factors predicting lymph nodes metastases, and (3) disease
      recurrence after thyroidectomy associated with radio-guided selective compartment
      neck dissection (RSCND). METHODS: We studied 345 consecutive PTC patients
      operated on between February 2004 and October 2011 at the S. Anna University
      Hospital, Ferrara (Italy). Patients with cervical lymph node metastases on
      preoperative ultrasonography and fine needle aspiration cytology were excluded.
      All patients underwent total thyroidectomy associated with SLN identification
      followed by RSCND in the SLN compartment, without SLN frozen section. RESULTS: In
      patients with lymph node metastases, metastatic nodes were not in the central
      neck compartment in 22.6% of the cases. The presence of infiltrating or
      multifocal PTC was a predicting factor for lymph nodes metastases. The median
      follow-up was 35.5 months. RSCND was associated with a false-negative rate of
      1.1%, a persistent disease rate of 0.6%, and a recurrent disease rate of 0.9%.
      The permanent dysphonia rate was 1.3%. CONCLUSION: RSCND associated with total
      thyroidectomy may improve: (1) the locoregional lymph node staging, and (2) the
      identification of the site of lymphatic drainage within the neck compartments.
      Thus, considering the high false-negative rate of sentinel lymph node biopsy
      (SLNB), a radio-guided technique in PTC patients may guide the lymphadenectomy
      (ie, RSCND) to increase the metastatic yield and improve staging of the disease
      rather than avoid prophylactic lymphadenectomy (ie, SLNB).

PMID- 24929765
TI  - Proficiency gain curve and predictors of outcome for laparoscopic ventral mesh
      rectopexy.
AB  - BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) is a well-recognized
      treatment for rectal prolapse and high-grade rectal intussusception. However, it
      is technically complex with the possibility of clinically relevant morbidity. The
      objectives were to define (i) the efficacy and safety of LVMR, (ii) risk factors
      for poor clinical outcome, and (iii) the autodidactic proficiency gain curve.
      METHODS: All primary LVMR cases performed by the senior author between January
      1997 and February 2013 were included in the study. In addition to the clinical
      outcomes, quality-of-life outcomes, including the Cleveland Clinic Incontinence
      Score and obstructive defecation syndrome score, were evaluated. Risk factors for
      operative complications, recurrence, and mesh-related complications were
      identified by the use of logistic regression models. Proficiency gain curves for
      functional and clinical outcomes were assessed using cumulative sum curves.
      RESULTS: A total of 636 LVMRs were performed during the study period. The mean
      percentage improvement in the Cleveland Clinic Incontinence Score and obstructive
      defecation syndrome score were 89.7% (SD 21.8%) and 56.7% (SD 20.6%). The
      operative complication, recurrent symptoms, and mesh-related complication rates
      were 9.9%, 9.4%, and 3.1%, respectively. Predictors of operative complication
      were male sex and previous abdominal operation; the only predictor of mesh
      related complications and recurrence was the use of polyester mesh. The learning
      curve for operative time was 54 cases, but for other clinical and quality-of-life
      outcomes was between 82 and 105 cases. CONCLUSION: LVMR treats rectal prolapse
      effectively, providing good symptomatic relief with minimal morbidity. However,
      the self-taught learning curve for this complex laparoscopic procedure is
      protracted.

PMID- 24929766
TI  - Impact of prothrombin time-International Normalized Ratio on outcome of patients
      with septic shock receiving polymyxin B cartridge hemoperfusion.
AB  - BACKGROUND: Although most patients with septic shock have a poor outcome, some
      may survive after blood purification treatment such as polymyxin B cartridge
      hemoperfusion (PMX). OBJECTIVE: To explore the most significant characteristic
      associated with 28-day mortality in patients with septic shock receiving PMX.
      METHODS: Between April 2006 and March 2008, 116 patients with septic shock who
      had received PMX in a prospectively collected multicenter collaborative study
      were enrolled. Uni- and multivariate analyses using the Cox proportional hazard
      model were performed to assess the most significant clinical characteristic that
      was associated with 28-day mortality. RESULTS: Among 33 clinicolaboratory
      characteristics, receiver operating characteristic (ROC) curve analyses selected
      12 characteristics with recommended cutoff values such as HCO(3)(-)
      (<=19.8/>19.8; mEq/L), base excess (<=-5.35/>-5.35; mEq/L), diastolic blood
      pressure (<=48/>48 mmHg), mean arterial pressure (<=73/>73 mmHg), pH
      (<=7.29/>7.29), interleukin-6 (<=19,150/>19,150 pg/dL), prothrombin time
      International Normalized Ratio (PT-INR; <=2.05/>2.05), predictive value of Acute
      Physiology and Chronic Health Evaluation II (APACHE II; <=0.4/>0.4), pyruvate
      (<=1.82/>1.82 mg/dL), APACHE II score (<=21/>21), acetate/pyruvate ratio
      (<=19/>19), and acetate (<=44.8/>44.8 mg/dL) on the basis of large area under the
      ROC curves for 28-day mortality. The results of uni- and multivariate analyses
      using these selected characteristics revealed that only PT-INR (<=2.05/>2.05;
      hazard ratio, 2.823; 95% CI, 1.243-6.412; P = .013) was associated with 28-day
      mortality. Survival curve analysis demonstrated a significant difference in 28
      day mortality between patients with lower (<=2.05) and higher (>2.05) PT-INR (P <
      .001). CONCLUSION: Prolonged PT-INR is an independent risk factor for 28-day
      mortality in patients receiving PMX for septic shock.

PMID- 24929767
TI  - Functional abdominal wall reconstruction improves core physiology and quality-of
      life.
AB  - INTRODUCTION: One of the goals of modern ventral hernia repair (VHR) is restoring
      the linea alba by returning the rectus muscles to the midline. Although this
      practice presumably restores native abdominal wall function, improvement of
      abdominal wall function has never been measured in a scientific fashion. We
      hypothesized that a dynamometer could be used to demonstrate an improvement in
      rectus muscle function after open VHR with restoration of the midline, and that
      this improvement would be associated with a better quality-of-life. METHODS:
      Thirteen patients agreed to dynamometric analysis before and 6 months after an
      open posterior component separation (Rives-Stoppa technique complimented with a
      transversus abdominis muscle release) and mesh sublay. Analysis done using a
      dynamometer (Biodex 3, Corp, Shirley, NY) included measurement of peak torque
      (PT; N*m) and PT per bodyweight (BW; %) generated during abdominal flexion in 5
      settings: Isokinetic analysis at 45 degrees /s and 60 degrees /s as well as
      isometric analysis at 0 degrees , -15 degrees , and +15 degrees . Power (W) was
      calculated during isokinetic settings. Quality-of-life was measured using our
      validated HerQles survey at the time of each dynamometric analysis. RESULTS:
      Thirteen patients (mean age, 54 +/- 9 years; mean body mass index, 31 +/- 7
      kg/m(2)) underwent repair with restoration of the midline using the
      aforementioned technique. Mean hernia width was 12.5 cm (range, 5-19).
      Improvements in PT and PT/BW were significant in all 5 settings (P < .05).
      Improvement in power during isokinetic analyses at 45 degrees /s and 60 degrees
      /s was also significant (P < .05). All patients reported an improvement in
      quality-of-life, which was associated positively with each dynamometric
      parameter. CONCLUSION: Restoration of the linea alba during VHR is associated
      with improved abdominal wall functionality. Analysis of rectus muscle function
      using a dynamometer showed statistical improvement by isokinetic and isometric
      measurements, all of which were associated with an improvement in quality-of
      life.

PMID- 24929768
TI  - Impact of analysis of frozen-section margin on reoperation rates in women
      undergoing lumpectomy for breast cancer: evaluation of the National Surgical
      Quality Improvement Program data.
AB  - BACKGROUND: Reoperation for positive margins after lumpectomy for breast cancer
      is common. Intraoperative analysis of frozen-section (FS) margins permits
      immediate re-excision, avoiding reoperation. The aim of this study was to compare
      reoperation rates between an institution using routine FS analysis of all margins
      and the National Surgical Quality Improvement Program (NSQIP) data. METHODS: We
      designed a retrospective cohort analysis comparing the NSQIP data from a FS
      single institution with the national NSQIP data from 2006 to 2010. Women
      undergoing lumpectomy for cancer were identified (N = 24,217), and reoperation
      rates were compared by the use of chi(2) analyses and multivariable logistic
      regression. During this time period, NSQIP did not differentiate between
      reoperations for complications or oncologic reasons. Reoperation rates for
      mastectomy patients (N = 21,734) and lumpectomy patients without cancer (N =
      2,777) over the same time period were analyzed as controls, because reoperations
      after these procedures likely would be for reasons other than positive margins.
      RESULTS: The 30-day reoperation rate after lumpectomy for cancer was greater
      nationally than at the FS institution (13.2% vs 3.6%, P < .001). Multivariable
      analysis showed that patients in the national NSQIP data set were over four times
      as likely to undergo reoperation as those at the FS institution's (odds ratio
      4.19). The reoperation rates were similar between the two, both for patients
      undergoing mastectomy (4.7% vs 4.5%, P = .84) and those undergoing lumpectomy for
      benign diagnosis (2.9% vs 5.9%, P = .39). CONCLUSION: Intraoperative FS margin
      analysis decreases the number of reoperations for patients undergoing breast
      conservation for breast cancer. This technique has important implications for
      patient satisfaction and cost of care.

PMID- 24929769
TI  - Heart rate variability parameters and ventricular arrhythmia correlate with
      pulmonary arterial pressure in adult patients with idiopathic pulmonary arterial
      hypertension.
AB  - OBJECTIVE: This aim of this study was to correlate heart rate variability (HRV)
      parameters to pulmonary arterial pressure (PAP) in patients with purely
      idiopathic pulmonary arterial hypertension (IPAH). BACKGROUND: HRV is decreased
      in patients with PAH. Whether HRV indices can be used to assess PAP in IPAH
      patients remains unclear. METHODS: HRV parameters obtained by 24-h ECG were
      evaluated in 26 IPAH patients and 51 controls. RESULTS: Time-domain HRV
      parameters (SDNN, p < 0.0001; SDANN, p < 0.0001; RMSSD, p = 0.006) were lower in
      IPAH patients. Frequency-domain indices (high-frequency power, HFP, p = 0.001;
      low-frequency power, LFP, p = 0.003; total power, TP, p = 0.001) were also
      decreased in IPAH patients. In IPAH patients, RMSSD (p = 0.001), HFP (p = 0.015),
      and LFP (p = 0.027) were significantly correlated with PAP. IPAH patients had
      longer QTc intervals (p < 0.0001) and more premature ventricular contractions (p
      < 0.0001) than controls. CONCLUSIONS: IPAH is associated with autonomic
      dysfunction. RMSSD, HFP, and LFP may be used as a supplemental tool to assess PAP
      in IPAH patients. IPAH patients with autonomic dysfunction are at high risk for
      ventricular arrhythmia.

PMID- 24929771
TI  - Characteristics of elderly fall patients with baseline mental status: high-risk
      features for intracranial injury.
AB  - BACKGROUND: Falls are a major cause of morbidity in the elderly. OBJECTIVES: We
      describe the low-acuity elderly fall population and study which historical and
      clinical features predict traumatic intracranial injuries (ICIs). METHODS: This
      is a prospective observational study of patients at least 65 years old presenting
      with fall to a tertiary care facility. Patients were eligible if they were at
      baseline mental status and were not triaged to the trauma bay. At presentation, a
      data form was completed by treating physicians regarding mechanism and position
      of fall, history of head strike, headache, loss of consciousness (LOC), and signs
      of head trauma. Radiographic imaging was obtained at the discretion of treating
      physicians. Medical records were subsequently reviewed to determine imaging
      results. All patients were called in follow-up at 30 days to determine outcome in
      those not imaged. The study was institutional review board approved. RESULTS: A
      total of 799 patients were enrolled; 79.5% of patients underwent imaging. Twenty
      seven had ICIs (3.4%). Fourteen had subdural hematoma, 7 had subarachnoid
      hemorrhage, 3 had cerebral contusion, and 3 had a combination of injuries.
      Logistic regression demonstrated 2 study variables that were associated with
      ICIs: LOC (odds ratio, 2.8; confidence interval, 1.2-6.3) and signs of head
      trauma (odds ratio, 13.2; confidence interval, 2.7-64.1). History of head strike,
      mechanism and position, headache, and anticoagulant and antiplatelet use were not
      associated with ICIs. CONCLUSION: Elderly fall patients who are at their baseline
      mental status have a low incidence of ICIs. The best predictors of ICIs are
      physical findings of trauma to the head and history of LOC.

PMID- 24929772
TI  - Acute psychosis presenting as a sole manifestation of left atrial myxoma: a new
      paradigm.
AB  - Atrial myxomas are the most common benign cardiac tumors. Neurological
      manifestations associated with left atrial myxoma are seen infrequently in the
      form of embolic stroke of intracranial hemorrhage. Psychiatric manifestations are
      however exceedingly rare. We hereby present a case who presented with acute
      psychosis as a sole manifestation of an underlying left atrial myxoma.

PMID- 24929773
TI  - TTP presenting as refractory hypoglycemia in a patient with thromboangiitis
      obliterans.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a challenging diagnosis to make in
      the emergency department. We present a case of TTP initially presenting with
      refractory hypoglycemia in a woman with thromboangiitis obliterans (Buerger's
      disease). To our knowledge, this is the first description of the association of
      hypoglycemia and thromboangiitis obliterans with TTP. We briefly review key
      aspects of the acute diagnosis and management of hypoglycemia and TTP pertinent
      to the emergency physician.

PMID- 24929774
TI  - Effects of uninterrupted chest compressions on the rescuer's physical condition.
AB  - STUDY OBJECTIVE: Recent guidelines have emphasized the need for uninterrupted
      chest compressions. The purpose of this study was to evaluate the rescuer's
      tolerability of uninterrupted chest compressions. METHODS: Twenty-five healthy
      subjects performed uninterrupted chest compressions for 7 minutes at a rate of
      100 compressions per minute using a training manikin. The quality of chest
      compressions was assessed in terms of the total number and percentage of chest
      compressions, compression depth, recoil distance, and duty cycle. Correct chest
      compression was defined as a depth of 38 to 51 mm. Physiological and laboratory
      parameters were measured before and after the procedure. Fatigue was measured
      using a numerical rating scale. Data were compared before and after the
      procedure. RESULTS: The participants were 10 emergency physicians and 15 medical
      students. The compression rate was nearly 100 compressions per minute. The number
      and percentage of correct compressions decreased gradually after 3 minutes. The
      compression depth decreased significantly after 2 minutes. The recoil distance
      and duty cycle were unchanged over 7 minutes. Systolic blood pressure, pulse
      rate, respiratory rate, numerical rating scale, serum lactate, adrenalin, and
      noradrenalin increased significantly after the procedure. Noradrenalin levels
      measured before the procedure were significantly and negatively correlated with
      the total number and percentage of correct compressions (r = -0.587, P = .004; r
      = -0.549, P = .008, respectively). CONCLUSIONS: Performing uninterrupted chest
      compressions for 7 minutes is an arduous procedure. Higher noradrenalin levels
      before the procedure might be associated with incorrect chest compressions.

PMID- 24929775
TI  - Emergency department recidivism in adults older than 65 years treated for
      fractures.
AB  - OBJECTIVES: Fractures in older adults are a commonly diagnosed injury in the
      emergency department (ED). We performed a retrospective medical record review to
      determine the rate of return to the same ED within 72 hours (returns) and the
      risk factors associated with returning. METHODS: A retrospective medical record
      review of patients at least 65 years old discharged from a large, academic ED
      with a new diagnosis of upper extremity, lower extremity, or rib fractures was
      performed. Risk factors analyzed included demographic data, type of fracture,
      analgesic prescriptions, assistive devices provided, other concurrent injuries,
      and comorbidities (Charlson Comorbidity Index). Our primary outcome was return to
      the ED within 72 hours. RESULTS: Three hundred fifteen patients qualified. Most
      fractures were in the upper extremity (64% [95% confidence interval {CI}, 58%
      69%]). Twenty patients (6.3% [95% CI, 3.9%-9.6%]) returned within 72 hours. Most
      returns (15/20, 75%) were for reasons associated with the fracture itself, such
      as cast problems and inadequate pain control. Only 3 (<1% of all patients)
      patients returned for cardiac etiologies. Patients with distal forearm fractures
      had higher return rates (10.7% vs 4.5%, P = .03), and most commonly returned for
      cast or splint problems. Age, sex, other injuries, assistive devices, and
      Charlson Comorbidity Index score (median, 1 [interquartile range, 1-2] for both
      groups) did not predict 72-hour returns. CONCLUSION: Older adults with distal
      forearm fractures may have more unscheduled health care usage in the first 3 days
      after fracture diagnosis than older adults with other fracture types. Overall,
      revisits for cardiac reasons or repeat falls were rare (<1%).

PMID- 24929776
TI  - The trauma nurse coordinator in England: a survey of demographics, roles and
      resources.
AB  - INTRODUCTION: Following the introduction of the regional trauma system in 2012
      the role of the trauma nurse coordinator (TNC) has been rolled out. This study
      aims to determine the demographic and practice profile of nurses performing the
      TNC role in England. METHODS: An electronic survey of TNCs across the 18 trauma
      networks in England was conducted. RESULTS: Fifty-three TNCs responded (62%) to
      the survey. Seventeen different role titles identified. The majority of TNCs had
      an emergency or trauma/orthopaedics clinical background. The largest proportion
      of time spent was clinical (38%). Least amount of time was spent in the education
      (7%), and research (3%). Nearly a quarter of respondents (23%) had some form of
      formal research training, nearly half (47%) were assisting others in research.
      Over half (55%) of respondents felt that they did not have adequate human
      resources to conduct their role. DISCUSSION: This research has provided baseline
      information about nurses in the role of TNC, their role titles and domains of the
      role 18 months after the formal introduction of trauma networks in England. There
      are some marked similarities and differences in the time spent in the different
      domains of the role between these findings and those published internationally.

PMID- 24929777
TI  - Overexpression of tomato chloroplast-targeted DnaJ protein enhances tolerance to
      drought stress and resistance to Pseudomonas solanacearum in transgenic tobacco.
AB  - DnaJ proteins as co-chaperones have critical functions in biotic and abiotic
      stress responses, but their biological functions remain largely uninvestigated.
      This study investigates the function of a tomato (Lycopersicon esculentum)
      chloroplast-targeted DnaJ protein (LeCDJ2) using transgenic tobacco. Quantitative
      real-time polymerase chain reaction analysis showed that LeCDJ2 expression was
      triggered by salicylic acid (SA), drought and pathogen attack. Ectopic expression
      of LeCDJ2 in transgenic tobacco reduced the accumulation of superoxide anion
      radical (O2(-)) and hydrogen peroxide (H2O2) under drought stress. Compared with
      Vec plants, the maximum photochemical efficiency of photosystem II (PSII)
      (Fv/Fm), net photosynthetic rate (Pn), and content of D1 protein were relatively
      higher in transgenic plants. The transgenic plants showes better growth, higher
      chlorophyll content, lower malondialdehyde (MDA) accumulation and relative
      electrolyte leakage (REL) under drought stress. In addition, overexpression of
      LeCDJ2 improved the resistance to the pathogen Pseudomonas solanacearum in
      transgenic tobacco. These results indicate that overexpression of a tomato
      chloroplast-targeted DnaJ gene enhances tolerance to drought stress and
      resistance to P. solanacearum in transgenic tobacco. 

PMID- 24929778
TI  - Survey of patient and physician influences and decision-making regarding CT
      utilization for minor head injury.
AB  - OBJECTIVE: Assess factors that influence both the patient and the physician in
      the setting of minor head injury in adults and the decision-making process around
      CT utilization. METHODS: This is a convenience sample survey study of adult minor
      head injury patients (GCS 15) and their physicians regarding factors influencing
      the decision to use CT to evaluate for intra-cranial haemorrhage. Once a head CT
      was ordered and before the results were known, both the patient and physician
      were given a one-page survey asking questions about their concern for injury and
      rationale for CT use. CT results and surveys were then recorded in a centralized
      database and analyzed. RESULTS: 584 subjects were enrolled over the 27-month
      study period. The rate of any intra-cranial haemorrhage was 3.3%. Both the
      physicians (6% pre-test estimate) and the patients (22% pre-test estimate) over
      estimated risk for haemorrhage. Clinical decision rules were not met in 46% of
      cases where CT was used. Physicians listed an average of 5 factors from a list of
      9 that influenced their decision to order CT. Patients listed an average of 1.7
      factors influencing their decision to present to the Emergency Department for
      evaluation. Many patients felt cost (45%) and low risk stratification (34%)
      should weigh heavily in the decision to use CT. If asked to limit CT utilization,
      physicians were able to identify a group with less than 2% risk of injury.
      CONCLUSIONS: Patients with low risk of intra-cranial injury continue to be
      evaluated by CT. Physician decision-making around the use of CT to evaluate minor
      head injury is multi-factorial. Shared decision-making between the patient and
      the physician in a low risk minor head injury encounter shows promise as a method
      to reduce CT utilization in this low risk cohort.

PMID- 24929779
TI  - Predictors of severe pain in the immediate postoperative period in elderly
      patients following hip fracture surgery.
AB  - INTRODUCTION: The aim of this study was to identify risk factors for severe
      postoperative pain immediately after hip-fracture surgery. PATIENTS AND METHODS:
      Three hundred forty-four elderly patients with an acute hip fracture were
      admitted to the hospital during a 12-months period. All patients who entered the
      study answered a structured questionnaire to assess demographic characteristics,
      previous diseases, drug use, previous surgery, and level of education. Physical
      status was assessed through the American Society of Anesthesiologists'
      preoperative risk classification, cognitive status using the Short Portable
      Mental Status Questionnaire, and depression using the Geriatric Depression Scale.
      The presence of preoperative delirium using the Confusion Assessment Method was
      assessed during day and night shifts until surgery. Pain was measured using a
      numeric rating scale (NRS). An NRS >= 7 one hour after surgery indicated severe
      pain. RESULTS: Patients with elementary-level education (8 yr in school)
      presented a higher risk for immediate severe postoperative pain than university
      educated patients (> 12 yr in school) (P < 0.05). Higher cognitive function was
      associated with higher postoperative pain (P < 0.01). Patients with symptoms of
      depression and patients with preoperative delirium presented a higher risk for
      severe pain (P < 0.05, P < 0.01, respectively). Multivariate analysis showed that
      depression and a low level of education were independent predictors of severe
      pain immediately after surgery. CONCLUSION: Depression and lower levels of
      education were independent predictors of immediate severe pain following hip
      fracture surgery. These predictors could be clinically used to stratify analgesic
      risk in elderly patients for more aggressive pain treatment immediately after
      surgery.

PMID- 24929781
TI  - Voluntary and involuntary emotional memory following an analogue traumatic
      stressor: the differential effects of communality in men and women.
AB  - BACKGROUND: Men and women show differences in performance on emotional processing
      tasks. Sex also interacts with personality traits to affect information
      processing. Here we examine effects of sex, and two personality traits that are
      differentially expressed in men and women - instrumentality and communality - on
      voluntary and involuntary memory for distressing video-footage. METHODS: On
      session one, participants (n = 39 men; 40 women) completed the Bem Sex-Role
      Inventory, which assesses communal and instrumental traits. After viewing film
      footage of death/serious injury, participants recorded daily involuntary memories
      (intrusions) relating to the footage on an online diary for seven days, returning
      on day eight for a second session to perform a voluntary memory task relating to
      the film. RESULTS: Communality interacted with sex such that men with higher
      levels of communality reported more frequent involuntary memories. Alternatively,
      a communality * sex interaction reflected a tendency for women with high levels
      of communality to perform more poorly on the voluntary recognition memory task.
      LIMITATIONS: The study involved healthy volunteers with no history of significant
      psychological disorder. Future research with clinical populations will help to
      determine the generalizability of the current findings. CONCLUSION: Communality
      has separate effects on voluntary and involuntary emotional memory. We suggest
      that high levels of communality in men and women may confer vulnerability to the
      negative effects of stressful events either through the over-encoding of
      sensory/perceptual-information in men or the reduced encoding of contextualised,
      verbally-based, voluntarily accessible representations in women.

PMID- 24929780
TI  - Afatinib in the treatment of EGFR mutation-positive NSCLC--a network meta
      analysis.
AB  - OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation-positive non-small
      cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by
      sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two
      reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family
      blocker afatinib are currently approved for treatment of EGFR mutation-positive
      NSCLC, but no head-to-head trials have been reported to date. We aimed to assess
      the relative efficacy of the three drugs by conducting a network meta-analysis
      (NMA). MATERIALS AND METHODS: A systematic literature review was conducted to
      identify all the available evidence. Outcomes of interest were progression-free
      survival (PFS) and overall survival. For PFS, results by investigator review were
      considered as not all trials assessed PFS independently. Results were analyzed
      using Bayesian methods. RESULTS: The literature search identified 246 articles
      that were assessed for eligibility, of which 21 studies were included in the NMA,
      including eight trials performed in an EGFR mutation-positive population. The
      estimated PFS HR (95% credible interval, CrI) for afatinib compared with
      gefitinib was 0.70 (0.40-1.16) and compared with erlotinib was 0.86 (0.50-1.50)
      in the total population. The estimated probability of being best for afatinib
      over all other treatments for PFS was 70% versus 27% for erlotinib and 3% for
      gefitinib; the estimated probability of chemotherapy being the best treatment was
      0%. Estimated HR (95% CrI) in patients with common mutations was 0.73 (0.42-1.24)
      for afatinib compared with erlotinib and 0.60 (0.34-0.99) for afatinib compared
      with gefitinib. OS findings were not significantly different between treatments.
      CONCLUSIONS: In the absence of direct head-to-head trial data comparing efficacy
      between the three EGFR TKIs, our analysis suggests that afatinib is a viable
      treatment alternative to erlotinib or gefitinib in terms of PFS. A direct trial
      based comparison of the efficacy of these agents is warranted to clarify their
      relative benefits.

PMID- 24929782
TI  - Further evidence for biased semantic networks in obsessive-compulsive disorder
      (OCD): when knives are no longer associated with buttering bread but only with
      stabbing people.
AB  - BACKGROUND AND OBJECTIVES: Semantic network models suggest that individuals with
      obsessive-compulsive disorder (OCD) process words with multiple meanings (e.g.,
      "knife") more likely in an OC-related (i.e., "weapon") than in a neutral way
      (i.e., "cutlery"). Initial evidence was found in an online study. The aim of the
      current study was to investigate semantic networks in a clinical OCD sample and
      particularly to identify whether changes in semantic networks following the add
      on intervention association splitting (AS) exceeded changes expected through
      cognitive behavioral therapy (CBT) alone. METHODS: An association task was
      presented to 36 healthy controls and 70 OCD patients over a period of eight weeks
      with OCD patients receiving CBT and an add-on intervention (randomized allocation
      to either AS or a computerized cognitive training). Participants were asked to
      generate up to five associations to standardized (OC-relevant, negative, neutral)
      and individual cue words. Associations were rated with regard to OC-relevance and
      valence. RESULTS: Analyses revealed that OCD participants produced a)
      significantly more OC-relevant associations and b) more negative associations
      than controls for cue words. In the OCD sample, the OC-relevance and valence of
      associations changed after therapy for personal cue words. This effect was
      associated with AS at statistical trend level. LIMITATIONS: No clinical control
      group was recruited; no inter-rater reliability was assessed for the association
      task. CONCLUSIONS: Further evidence for biased associative networks in OCD was
      found. Associations of individually chosen cue words proved to be modifiable by
      therapy.

PMID- 24929783
TI  - Exploring the cognitive load of negative thinking: a novel dual-task experiment.
AB  - BACKGROUND AND OBJECTIVES: Females are more likely to engage in the preoccupation
      of past negative experiences than males, which might contribute to their greater
      tendency toward depression. However, there is limited understanding regarding the
      cognitive basis for the negative autobiographical information processing of
      females. In the present study, we assessed the cognitive resources required for
      negative thinking, by using a novel dual-task paradigm that combined think-aloud
      and time-estimation tasks. METHODS: Fifty-three Japanese undergraduate students
      were asked to think aloud about personal past or future emotional episodes for a
      particular duration. In addition, they were asked to estimate the duration of
      their speech. Their estimates were compared to the actual time taken, and the
      errors were used as indices of cognitive burden during the speech task. RESULTS:
      As compared to males, females exhibited greater judgment errors, particularly
      when thinking about their past negative experiences. This suggests that females
      allocate more attentional resources toward thinking about the past. LIMITATIONS:
      Participants could rehearse the task during the time reproduction phase, and the
      quality of the rehearsal and their memory capacity might have influenced the
      accuracy of their duration judgment. CONCLUSIONS: Females tend to allocate more
      attentional resources than males to thinking about past negative episodes, which
      in turn might be associated with reduced availability of resources for central
      cognitive control processes such as inhibition of and switching away from
      processing of negative autobiographical information.

PMID- 24929784
TI  - Stabilizing conditions of metal mercury in mercury sulfurization using a
      planetary ball mill.
AB  - This study used a non-heating process to stabilize mercury by mercury
      sulfurization. Elemental mercury and sulfur were mixed using planetary ball
      milling under various experimental conditions and the optimal conditions were
      determined. The labile intermediate, mercury sulfide, was observed in the early
      stages of milling, and the intermediates were then pulverized into mercury
      sulfide powder. These phenomena were significantly influenced by the diameter of
      the planetary ball. A larger diameter enhanced mercury stabilization. For a ball
      with a 19.04-mm diameter, the toxicity characteristic leaching procedure (TCLP)
      and the Japanese leaching test (JLT) values were 0.263MUg/L and 0.0586MUg/L,
      respectively, suggesting that mercury leachability was strictly controlled. When
      the molar ratio of sulfur to mercury was 1.05, the mercury concentration in the
      headspace was <1MUg/Nm(3) at 20 degrees C, which was equivalent to the level in
      pure reagent. The stability of the planetary ball milling product at optimum
      conditions was either comparable or superior to that in other stabilization
      techniques. The running cost of this technology was estimated to be 15,360Yen
      (154USD)/ton-Hg. This stabilization technology is cost-effective and
      environmentally sound for the long-term and safe management of mercury. 

PMID- 24929785
TI  - Probability analysis of multiple-tank-car release incidents in railway hazardous
      materials transportation.
AB  - Railroads play a key role in the transportation of hazardous materials in North
      America. Rail transport differs from highway transport in several aspects, an
      important one being that rail transport involves trains in which many railcars
      carrying hazardous materials travel together. By contrast to truck accidents, it
      is possible that a train accident may involve multiple hazardous materials cars
      derailing and releasing contents with consequently greater potential impact on
      human health, property and the environment. In this paper, a probabilistic model
      is developed to estimate the probability distribution of the number of tank cars
      releasing contents in a train derailment. Principal operational characteristics
      considered include train length, derailment speed, accident cause, position of
      the first car derailed, number and placement of tank cars in a train and tank car
      safety design. The effect of train speed, tank car safety design and tank car
      positions in a train were evaluated regarding the number of cars that release
      their contents in a derailment. This research provides insights regarding the
      circumstances affecting multiple-tank-car release incidents and potential
      strategies to reduce their occurrences. The model can be incorporated into a
      larger risk management framework to enable better local, regional and national
      safety management of hazardous materials transportation by rail. 

PMID- 24929786
TI  - The zeta potential of mineral fibres.
AB  - For the first time, the zeta (xi) potential of pathogenic mineral fibres
      (chrysotiles, amphiboles and erionite) was systematically investigated to shed
      light on the relationship between surface reactivity and fibre pathogenicity. A
      general model explaining the zeta potential of chrysotile, amphiboles and
      erionite has been postulated. In double distilled water, chrysotiles showed
      positive values while crocidolite and erionite showed negative values. In contact
      with organic solutions, all fibres exhibited negative values of zeta potential.
      The decrease of the surface potential is deemed to be a defensive chemical
      response of the macrophage cells to minimize hemolytic damage. Negatively charged
      surfaces favour the binding of collagen and redox activated Fe-rich proteins, to
      form the so-called asbestos bodies and prompt the formation of HO via the
      reaction with peroxide (H2O2+e(-)->HO+HO(-)). An additional mechanism accounting
      for higher carcinogenicity is possibly related to the Ca(2+) sequestration by the
      fibres with surface negative potential, impairing the mitochondrial apoptotic
      pathway. It was also found that with a negative zeta potential, the attractive
      forces prevailed over repulsions and favoured processes such as agglomeration
      responsible of a tumorigenic chronic inflammation. 

PMID- 24929787
TI  - Evaluation of a novel chitosan-based flocculant with high flocculation
      performance, low toxicity and good floc properties.
AB  - In this work, a novel chitosan-based flocculant, carboxymethyl chitosan-graft
      poly[(2-methacryloyloxyethyl) trimethyl ammonium chloride] (CMC-g-PDMC), was
      designed and prepared successfully. Flocculation performance of CMC-g-PDMC was
      systematically evaluated using kaolin suspension, humic acid (HA) solution and
      kaolin-HA mixed suspension as synthetic wastewater under acidic, neutral and
      alkaline conditions, respectively. The experimental results demonstrated that CMC
      g-PDMC exhibited lower optimal dosage, higher contaminant removal efficiency,
      wider applicable pH range, lower effluent toxicity and better floc properties for
      handling and disposal, in comparison with polyaluminum chloride. The high
      flocculation performance of CMC-g-PDMC was ascribed to two structural advantages
      of improved both positive charges and molecular weight. In addition, flocs
      characteristics including flocs formation, breakage, regrowth and fractal
      structure, were studied by an in-situ light scattering system during the
      flocculation process. Detailed analysis clearly illuminated the differences and
      relationship among floc size, fractal dimension and floc strength. Based on
      analysis of floc properties in combination with zeta potential measurements,
      flocculation mechanisms in different synthetic wastewater at various pHs were
      deeply discussed: charge neutralization or patching played the key role under
      different conditions, and the relationship between flocculation mechanisms and
      floc properties has been built. The effective and environment-friendly flocculant
      bear significant application potentials in water treatment fields. 

PMID- 24929788
TI  - Biosurfactant produced by novel Pseudomonas sp. WJ6 with biodegradation of n
      alkanes and polycyclic aromatic hydrocarbons.
AB  - Alkanes and polycyclic aromatic hydrocarbons (PAHs) have threatened the
      environment due to toxicity and poor bioavailability. Interest in degradation of
      these hazardous materials by biosurfactant-producing bacteria has been steadily
      increasing in recent years. In this work, a novel biosurfactant-producing
      Pseudomonas sp. WJ6 was isolated to degrade a wide range of n-alkanes and
      polycyclic aromatic hydrocarbons. Production of lipopeptide biosurfactant was
      observed in all biodegradable studies. These lipopeptides were purified and
      identified by C18 RP-HPLC system and electrospray ionization-mass spectrometry.
      Results of structural analysis showed that these lipopeptides generated from
      different hydrocarbons were classified to be surfactin, fengycin and lichenysin.
      Heavy-oil sludge washing experiments demonstrated that lipopeptides produced by
      Pseudomonas sp. WJ6 have 92.46% of heavy-oil washing efficiency. The obtained
      results indicate that this novel bacterial strain and its lipopeptides have great
      potentials in the environmental remediation and petroleum recovery. 

PMID- 24929789
TI  - Characterization of pharmaceuticals and personal care products as N
      nitrosodimethylamine precursors during disinfection processes using free chlorine
      and chlorine dioxide.
AB  - The worldwide detection of pharmaceuticals and personal care products (PPCPs) in
      aquatic environment and drinking water has caused wide concern in recent years.
      The possibility for concurrent formation of N-nitrosodimethylamine (NDMA) during
      disinfection has become another significant concern for water quality. This study
      demonstrates that a group of PPCPs containing amine groups can serve as NDMA
      precursors during free chlorine or chlorine dioxide (ClO2) chlorination
      processes. Selected PPCPs after screening by NDMA yield were further investigated
      for NDMA formation conditions. High disinfectant dose and initial PPCP
      concentration resulted in relatively high NDMA formation potential. Linear
      kinetic models were developed for NDMA formation during chlorination of selected
      PPCPs. Although the PPCP precursors were removed significantly during
      chlorination, they were not completely mineralized based on the total organic
      carbon (TOC) loss. The existence of another possible pathway for direct formation
      of NDMA from tertiary amine during chlorination was indicated, in which
      dimethylamine (DMA) was not involved. It is recommended to control the initial
      PPCP concentrations prior to disinfection and to shorten the contact time to
      reduce the NDMA formation. ClO2 is suggested to be a proper disinfectant in order
      to reduce the NDMA formation. 

PMID- 24929790
TI  - Effect of acute beer ingestion on the liver: studies in female mice.
AB  - PURPOSE: The aim of the present study was to assess whether the effects of acute
      consumption of stout or pilsner beer on the liver differ from those of plain
      ethanol in a mouse model. METHODS: Seven-week-old female C57BL/6J mice received
      either ethanol, stout or pilsner beer (ethanol content: 6 g/kg body weight) or
      isocaloric maltodextrin solution. Plasma alanine transaminase, markers of
      steatosis, lipogenesis, activation of the toll-like receptor-4 signaling cascade
      as well as lipid peroxidation and fibrogenesis in the liver were measured 12 h
      after acute ethanol or beer intake. RESULTS: Acute alcohol ingestion caused a
      marked ~11-fold increase in hepatic triglyceride accumulation in comparison to
      controls, whereas in mice exposed to stout and pilsner beer, hepatic triglyceride
      levels were increased only by ~6.5- and ~4-fold, respectively. mRNA expression of
      sterol regulatory element-binding protein 1c and fatty acid synthase in the liver
      did not differ between alcohol and beer groups. In contrast, expression of
      myeloid differentiation primary response gene 88, inducible nitric oxide
      synthases, but also the concentrations of 4-hydroxynonenal protein adducts,
      nuclear factor kappaB and plasminogen activator inhibitor-1 were induced in
      livers of ethanol treated mice but not in those exposed to the two beers.
      CONCLUSION: Taken together, our results suggest that acute ingestion of beer and
      herein especially of pilsner beer is less harmful to the liver than the ingestion
      of plain ethanol.

PMID- 24929791
TI  - Ultrasound assisted direct oxidative esterification of aldehydes and alcohols
      using graphite oxide and Oxone.
AB  - A sonochemical procedure for direct oxidative esterification of aldehydes and
      alcohols using graphite oxide and Oxone in an alcoholic solvent is described.
      Mild reaction conditions, short reaction times, cost-effectiveness, and facile
      isolation of the products make the present system as a practical method. 

PMID- 24929793
TI  - ADHD and personality: a meta-analytic review.
AB  - We report a meta-analysis of up to 40 data sets that examined the personality
      dimensions in the Five-Factor Model (FFM) and the integrated Five-Factor Model
      (IFFM) in relation to ADHD symptom domains of inattention (IA) and
      hyperactivity/impulsivity (HI). The IFFM incorporated the dimensions of other
      personality models (in particular, those of Eysenck, Tellegen, and Cloninger, as
      well as the FFM). Major findings were: (1) IA and HI were both associated with
      low conscientious inhibition/conscientiousness, and low agreeable
      inhibition/agreeableness, and with high negative emotionality/neuroticism; (2)
      conscientious inhibition and conscientiousness were more strongly related to IA
      than HI; (3) agreeable inhibition and agreeableness were more strongly related to
      HI than IA; and (4) the association of conscientious inhibition and
      conscientiousness with HI was moderated by age group and source from where
      participants were recruited (associations were stronger in children than adults,
      and clinical samples than community samples). These findings are discussed in
      relation to single and multiple pathway theories, underlying factors and
      processes for the personality-ADHD link, and clinical implications. 

PMID- 24929792
TI  - Variation block-based genomics method for crop plants.
AB  - BACKGROUND: In contrast with wild species, cultivated crop genomes consist of
      reshuffled recombination blocks, which occurred by crossing and selection
      processes. Accordingly, recombination block-based genomics analysis can be an
      effective approach for the screening of target loci for agricultural traits.
      RESULTS: We propose the variation block method, which is a three-step process for
      recombination block detection and comparison. The first step is to detect
      variations by comparing the short-read DNA sequences of the cultivar to the
      reference genome of the target crop. Next, sequence blocks with variation
      patterns are examined and defined. The boundaries between the variation
      containing sequence blocks are regarded as recombination sites. All the assumed
      recombination sites in the cultivar set are used to split the genomes, and the
      resulting sequence regions are termed variation blocks. Finally, the genomes are
      compared using the variation blocks. The variation block method identified
      recurring recombination blocks accurately and successfully represented block
      level diversities in the publicly available genomes of 31 soybean and 23 rice
      accessions. The practicality of this approach was demonstrated by the
      identification of a putative locus determining soybean hilum color. CONCLUSIONS:
      We suggest that the variation block method is an efficient genomics method for
      the recombination block-level comparison of crop genomes. We expect that this
      method will facilitate the development of crop genomics by bringing genomics
      technologies to the field of crop breeding.

PMID- 24929794
TI  - Clinically assessed consequences of workplace physical violence.
AB  - OBJECTIVES: To assess consequences of physical violence at work and identify
      their predictors. METHODS: Among the patients in a medicolegal consultation from
      2007 to 2010, the subsample of workplace violence victims (n = 185) was
      identified and contacted again in average 30 months after the assault. Eighty-six
      victims (47 %) participated. Ordinal logistic regression analyses assessed the
      effect of 9 potential risk factors on physical, psychological and work
      consequences summarized in a severity score (0-9). RESULTS: Severity score
      distribution was as follows: 4+: 14 %; 1-3: 42 %; and 0: 44 %. Initial
      psychological distress resulting from the violence was a strong predictor (p <
      0.001) of the severity score both on work and long-term psychological
      consequences. Gender and age did not reach significant levels in multivariable
      analyses even though female victims had overall more severe consequences.
      Unexpectedly, only among workers whose jobs implied high awareness of the risk of
      violence, first-time violence was associated with long-term psychological and
      physical consequences (p = 0.004). Among the factors assessed at follow-up,
      perceived lack of employers' support or absence of employer was associated with
      higher values on the severity score. The seven other assessed factors (initial
      physical injuries; previous experience of violence; preexisting health problems;
      working alone; internal violence; lack of support from colleagues; and lack of
      support from family or friends) were not significantly associated with the
      severity score. CONCLUSIONS: Being a victim of workplace violence can result in
      long-term consequences on health and employment, their severity increases with
      the seriousness of initial psychological distress. Support from the employer can
      help prevent negative outcomes.

PMID- 24929795
TI  - Effect of short-term synbiotic treatment on plasma p-cresol levels in patients
      with chronic renal failure: a randomized clinical trial.
AB  - BACKGROUND AND AIMS: In patients with chronic kidney disease (CKD), alterations
      in gut microbiome are posited to be responsible for gastrointestinal symptoms and
      generation of p-cresol, a uremic toxin that has been associated with CKD
      progression and cardiovascular mortality. This pilot study investigated whether
      Probinul-neutro(r), a synbiotic that normalizes intestinal microflora, may lower
      plasma p-cresol concentrations and reduce gastrointestinal symptoms in non
      dialyzed CKD patients. METHODS AND RESULTS: This was a double-blind, randomized
      placebo-controlled trial. Thirty patients on 3-4 CKD stages were randomized to
      receive either Probinul neutro(r) or placebo for 4 weeks. Total plasma p-cresol
      concentration was assessed at baseline, and 15 and 30 days after treatment start.
      At the same study times, ease and frequency of defecation, upper and lower
      abdominal pain, stool shape, borborygmi, and flatus were quantified by subjective
      assessment questionnaires. Compared to baseline total plasma p-cresol median
      concentrations on 15th and 30th day were significantly lower in patients
      receiving Probinul-neutro(r) (2.31 and 0.78 vs. 3.05 MUg/ml, p < 0.05; n = 18);
      no changes of plasma p-cresol concentrations were recorded in placebo-treated
      patients. No significant changes in gastrointestinal symptoms were observed
      during the study both in Probinul-neutro(r)-treated and placebo-treated patients.
      CONCLUSION: Probinul-neutro(r) lowered total plasma p-cresol concentrations but
      did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients.
      Because high plasma concentrations of p-cresol in early phases of CKD are
      predictive of progression to end-stage renal disease, the results of our study
      suggest that synbiotics deserve attention as possible tools to delay CKD
      progression towards end-stage renal disease (ESRD). CLINICALTRIALSGOV IDENTIFIER:
      NCT02008331.

PMID- 24929796
TI  - Effects of continuous prostacyclin infusion on regional blood flow and cerebral
      vasospasm following subarachnoid haemorrhage: statistical analysis plan for a
      randomized controlled trial.
AB  - BACKGROUND: One of the main causes of mortality and morbidity following
      subarachnoid hemorrhage (SAH) is the development of cerebral vasospasm, a
      frequent complication arising in the weeks after the initial bleeding. Despite
      extensive research, no effective treatment of vasospasm exists to date.
      Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In
      vitro models have shown a relaxing effect of prostacyclin after induced
      contraction in cerebral arteries, and a recent pilot trial showed a positive
      effect on cerebral vasospasm in a clinical setting. No randomized clinical trials
      have investigated the possible pharmacodynamic effects of prostacyclin on the
      human brain following SAH. METHODS/DESIGN: This trial is a single centre,
      randomized, placebo-controlled, parallel group, double blinded, clinical pilot
      trial. A total of 90 patients with SAH will be randomized to one of three
      intervention arms: epoprostenol at 1 ng/kg/min, epoprostenol at 2 ng/kg/min, or
      placebo in addition to the standard treatment. Trial medication will start on Day
      5 after SAH and continue to Day 10. The primary outcome measure is changes in
      cerebral blood flow measured by a computed tomography (CT) perfusion scan. The
      secondary outcomes are vasospasm measured by a CT angiography, regional blood
      flow, clinical symptoms of cerebral ischemia, and outcome at three months
      (Glasgow Outcome Scale). DISCUSSION: The primary outcome has been altered
      slightly since the publication of our study protocol. Global cerebral blood flow
      is now primary outcome, whereas regional blood flow is a secondary outcome. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01447095. Registration date: 11 October 2011.

PMID- 24929797
TI  - Disease burden of urinary tract infections among type 2 diabetes mellitus
      patients in the U.S.
AB  - AIMS: Type 2 diabetes is a reported risk factor for more frequent and severe
      urinary tract infections (UTI). We sought to quantify the annual healthcare cost
      burden of UTI in type 2 diabetic patients. METHODS: Adult patients diagnosed with
      type 2 diabetes were identified in MarketScan administrative claims data. UTI
      occurrence and costs were assessed during a 1-year period. We examined UTI
      related visit and antibiotic costs among patients diagnosed with UTI, comparing
      those with versus without a history of UTI in the previous year (prevalent vs.
      incident UTI cases). We estimated the total incremental cost of UTI by comparing
      all-cause healthcare costs in patients with versus without UTI, using propensity
      score-matched samples. RESULTS: Within the year, 8.2% (6,014/73,151) of subjects
      had >=1 UTI, of whom 33.8% had a history of UTI. UTI-related costs among
      prevalent versus incident cases were, respectively, $603 versus $447 (p=0.033)
      for outpatient services, $1,607 versus $1,819 (p=NS) for hospitalizations, and
      $61 versus $35 (p<0.0001) for antibiotics. UTI was associated with a total all
      cause incremental cost of $7,045 (95% CI: 4,130, 13,051) per patient with UTI per
      year. CONCLUSIONS: UTI is common and may impose a substantial direct medical cost
      burden among patients with type 2 diabetes.

PMID- 24929798
TI  - Exercise improves gait, reaction time and postural stability in older adults with
      type 2 diabetes and neuropathy.
AB  - AIMS: For older adults with type 2 diabetes (T2DM), declines in balance and
      walking ability are risk factors for falls, and peripheral neuropathy magnifies
      this risk. Exercise training may improve balance, gait and reduce the risk of
      falling. This study investigated the effects of 12weeks of aerobic exercise
      training on walking, balance, reaction time and falls risk metrics in older T2DM
      individuals with/without peripheral neuropathy. METHODS: Adults with T2DM, 21
      without (DM; age 58.7+/-1.7years) and 16 with neuropathy (DM-PN; age 58.9+/
      1.9years), engaged in either moderate or intense supervised exercise training
      thrice-weekly for 12weeks. Pre/post-training assessments included falls risk
      (using the physiological profile assessment), standing balance, walking ability
      and hand/foot simple reaction time. RESULTS: Pre-training, the DM-PN group had
      higher falls risk, slower (hand) reaction times (232 vs. 219ms), walked at a
      slower speed (108 vs. 113cm/s) with shorter strides compared to the DM group.
      Following training, improvements in hand/foot reaction times and faster walking
      speed were seen for both groups. CONCLUSIONS: While falls risk was not
      significantly reduced, the observed changes in gait, reaction time and balance
      metrics suggest that aerobic exercise of varying intensities is beneficial for
      improving dynamic postural control in older T2DM adults with/without neuropathy.

PMID- 24929799
TI  - Improving inhaler adherence in patients with chronic obstructive pulmonary
      disease: a cost-effectiveness analysis.
AB  - BACKGROUND: The PHARMACOP-intervention significantly improved medication
      adherence and inhalation technique for patients with COPD compared with usual
      care. This study aimed to evaluate its cost-effectiveness. METHODS: An economic
      analysis was performed from the Belgian healthcare payer's perspective. A Markov
      model was constructed in which a representative group of patients with COPD (mean
      age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume
      in 1 second of % predicted of 50), was followed for either receiving the 3-month
      PHARMACOP-intervention or usual care. Three types of costs were calculated:
      intervention costs, medication costs and exacerbation costs. Outcome measures
      included the number of hospital-treated exacerbations, cost per prevented
      hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up
      was 1 year in the basecase analysis. Sensitivity and scenario analyses (including
      long-term follow-up) were performed to assess uncertainty. RESULTS: In the
      basecase analysis, the average overall costs per patient for the PHARMACOP
      intervention and usual care were ?2,221 and ?2,448, respectively within the 1
      year time horizon. This reflects cost savings of ?227 for the PHARMACOP
      intervention. The PHARMACOP-intervention resulted in the prevention of 0.07
      hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for
      usual care). Results showed robust cost-savings in various sensitivity analyses.
      CONCLUSIONS: Optimization of current pharmacotherapy (e.g. close monitoring of
      inhalation technique and medication adherence) has been shown to be cost-saving
      and should be considered before adding new therapies.

PMID- 24929800
TI  - Radiolucent esophageal foreign body presenting as a middle mediastinal mass and
      tracheoesophageal fistula.

PMID- 24929801
TI  - Effect of early and intensive continuous venovenous hemofiltration on patients
      with cardiogenic shock and acute kidney injury after cardiac surgery.
AB  - OBJECTIVE: Continuous renal replacement therapy (CRRT) is currently the mainstay
      renal support for critically ill patients. However, the optimal intensity of CRRT
      remains debated owing to the heterogeneity of the study populations and CRRT
      techniques across centers. The present study investigated the beneficial effects
      of early and intensive continuous venovenous hemofiltration (CVVH) on patients
      with shock after cardiotomy. METHODS: Patients who had received CRRT for
      cardiogenic shock and acute kidney injury after cardiac surgery from January 2003
      to December 2007 were retrospectively recruited. They were divided into 2 groups
      according to the delivered dosage of hemofiltration. RESULTS: The mean duration
      between intensive care unit admission and initiation of CVVH was 1.4+/-0.8 days.
      The all-cause mortality by day 30 was 73.3% and 45.4% in the low- and high-dose
      groups, respectively (P=.002). The corresponding in-hospital mortality rate was
      82.2% and 61.8% (P=.02). No significant difference was seen in the renal recovery
      of the survivors between the 2 groups. CONCLUSIONS: In patients developing
      postoperative cardiogenic shock and acute kidney injury after cardiac surgery, an
      early higher CVVH dose was associated with better in-hospital and long-term
      survival. Moreover, the beneficial effect of intensive treatment might be more
      critical in the early perioperative period.

PMID- 24929802
TI  - A novel hybrid technique for transcatheter pulmonary valve implantation within a
      dilated native right ventricular outflow tract.

PMID- 24929803
TI  - Should integrated residency programs supplant traditional programs in
      cardiothoracic surgery?

PMID- 24929804
TI  - Preoperative transcatheter occlusion of bronchopulmonary collateral artery
      reduces reperfusion pulmonary edema and improves early hemodynamic function after
      pulmonary thromboendarterectomy.
AB  - OBJECTIVE: The present study assessed the effectiveness of preoperative
      transcatheter occlusion of the bronchopulmonary collateral artery (PTOBPCA) in
      reducing reperfusion pulmonary edema after pulmonary thromboendarterectomy (PEA).
      METHODS: The data from 155 patients with chronic thromboembolic pulmonary
      hypertension at Anzhen Hospital, treated from January 2007 to August 2013, with
      PEA were retrospectively reviewed. The patients were classified into a control
      (group A, n = 87) and treated (group B, underwent PTOBPCA, n = 68) group. The
      reperfusion pulmonary edema incidence, mechanical ventilation and intensive care
      unit hospitalization duration, and hemodynamic function were compared between the
      2 groups. RESULTS: Of the 87 patients in group A, 5 died in-hospital (5.7%
      mortality); no patient in group B died (0% mortality; P = .035). In group A, 9
      patients (10.3%) required extracorporeal membrane oxygenation (ECMO) after PEA; 1
      patient (1.5%) in group B required ECMO (chi-square test, P = .026, chi(2) =
      4.980). Group B had shorter intubation and intensive care unit hospitalization
      times, lower mean pulmonary artery pressures and pulmonary vascular resistance,
      higher partial pressures of oxygen in arterial blood and oxygen saturation, and
      decreased medical expenditure compared with group A. During a mean 37.1 +/- 21.4
      months of follow-up, 3 patients in group A and 2 in group B died; however, the
      difference in the actuarial survival at 3 years postoperatively between the 2
      groups was not statistically significant. CONCLUSIONS: PTOBPCA can reduce the
      incidence of reperfusion pulmonary edema, shorten intensive care unit
      hospitalization and intubation duration, improve early hemodynamic function, and
      reduce ECMO usage after PEA.

PMID- 24929805
TI  - Alterations of the daily rhythms of HPT axis induced by chronic unpredicted mild
      stress in rats.
AB  - The relationship between thyroid function and depression has long been
      recognized. Patients with thyroid disorders are more prone to develop depressive
      symptoms and conversely depression may be accompanied by various subtle thyroid
      abnormalities. However, the daily rhythm alteration of the functions of the
      hypothalamus pituitary thyroid axis (HPT) is uncertain. In the present study, we
      investigated the effects of chronic unpredictable mild stress (CUMS) on the daily
      rhythm alterations of triiodothyronine (T3), thyroxine (T4), and Thyroid
      Stimulating Hormone (TSH) in the plasma. We found that CUMS led to depressive
      like behavior and the daily rhythm of T3, T4, and TSH in the plasma being
      disturbed, as well the plasma levels of T3 and T4 decreased compared to control
      group. Our findings indicate that CUMS not only induce hypofunction of HPT axis
      but also the disturbance of daily rhythm of PHT axis in rats. 

PMID- 24929806
TI  - Comparative analysis of vaspin in pregnant women with and without gestational
      diabetes mellitus and healthy non-pregnant women.
AB  - To explore serum vaspin, leptin, and adiponectin levels and their correlation
      with insulin resistance (IR) in pregnant women with and without gestational
      diabetes mellitus (GDM) and healthy non-pregnant women. A total of 262
      individuals, including pregnant women with GDM (n = 86), those without GDM (n =
      92), and age-matched healthy non-pregnant women (n = 84) were enrolled in this
      case-control study. Vaspin, leptin, adiponectin, glucose, insulin, hemoglobin A1C
      (HbA1c), and lipid parameters were measured. The homeostasis model assessment
      insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and
      body mass index were calculated. Data inferred higher concentrations of vaspin
      (2.72 +/- 2.20 vs. 1.84 +/- 1.57 vs. 0.81 +/- 1.02) in GDM than during normal
      pregnancy and in non-pregnant women, higher leptin (23.42 +/- 12.18 vs. 22.19 +/-
      10.55 vs. 12.10 +/- 11.26), and lower adiponectin (4,164.83 +/- 2,650.39 vs.
      4,871.66 +/- 2,803.51 vs. 7,202.85 +/- 4,893.13) in GDM and normal pregnancy as
      compared to non-pregnant women (p < 0.05). Vaspin was positively correlated to
      leptin (r = 0.273, p = 0.012), HOMA-IR (r = 0.387, p = 0.000), and triglycerides
      (TG, r = 0.218, p = 0.046) in GDM. In addition, leptin was negatively correlated
      to adiponectin in GDM (r = -0.336, p = 0.002) and normal pregnancy (r = -0.256, p
      = 0.014). Furthermore, vaspin was significantly correlated to GDM and HOMA-IR,
      and the weight gain might play a vital role in the occurrence of GDM. During
      pregnancy, high vaspin concentration is significantly associated with IR in GDM.

PMID- 24929807
TI  - Network-dosage compensation topologies as recurrent network motifs in natural
      gene networks.
AB  - BACKGROUND: Global noise in gene expression and chromosome duplication during
      cell-cycle progression cause inevitable fluctuations in the effective number of
      copies of gene networks in cells. These indirect and direct alterations of
      network copy numbers have the potential to change the output or activity of a
      gene network. For networks whose specific activity levels are crucial for
      optimally maintaining cellular functions, cells need to implement mechanisms to
      robustly compensate the effects of network dosage fluctuations. RESULTS: Here, we
      determine the necessary conditions for generalized N-component gene networks to
      be network-dosage compensated and show that the compensation mechanism can
      robustly operate over large ranges of gene expression levels. Furthermore, we
      show that the conditions that are necessary for network-dosage compensation are
      also sufficient. Finally, using genome-wide protein-DNA and protein-protein
      interaction data, we search the yeast genome for the abundance of specific dosage
      compensation motifs and show that a substantial percentage of the natural
      networks identified contain at least one dosage-compensation motif. CONCLUSIONS:
      Our results strengthen the hypothesis that the special network topologies that
      are necessary for network-dosage compensation may be recurrent network motifs in
      eukaryotic genomes and therefore may be an important design principle in gene
      network assembly in cells.

PMID- 24929808
TI  - Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in
      spinal chordoma.
AB  - PURPOSE: To clarify whether vascular endothelial growth factor receptor 2
      (VEGFR2) and inducible nitric oxide synthase (iNOS) are involved in the
      angiogenesis and recurrence of spinal chordoma tissues and influence the overall
      survival. METHODS: All patients affected by a spinal chordoma surgically treated
      between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and
      iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma
      samples. Local recurrence and overall survival (OS) were analyzed. RESULTS: A
      series of 40 chordoma patients who underwent surgery for a total of 120 lesions
      (including 80 recurrent lesions) were identified (sacrum 77.5 %, lumbar spine
      17.5 %, cervical/thoracic spine 5 %). Surgical margins were wide in 30 (75 %),
      marginal in 8 (20 %) and intralesional in 2 (5 %) patients. Median follow-up was
      120 months. The 5- and 10-year OS of the entire series of patients was 78.6 and
      30 %, respectively. There were five primary chordomas (12.5 %) with moderate and
      35 (87.5 %) with strong expression of VEGFR-2. All recurrent spinal chordomas
      displayed strong expression of VEGFR-2. The expression of iNOS was predominately
      moderate to high in primary chordomas: There were 15 tumors (37.5 %) with
      moderate and 25 tumors (62.5 %) with strong expression. All recurrent chordomas
      displayed strong expression of iNOS. CONCLUSION: The high expression of VEGFR-2
      and iNOS affected the OS. The OS at 10 years was only 30 %.

PMID- 24929809
TI  - Effects of sludge retention times on reactivity of effluent dissolved organic
      matter for trihalomethane formation in hybrid powdered activated carbon membrane
      bioreactors.
AB  - In this study, real municipal wastewater intended for reuse was treated by two
      identical hybrid PAC/MBRs (membrane bioreactors with powdered activated carbon
      addition), which were operated at sludge retention times (SRTs) of 30 and 180
      days, respectively. In order to investigate the effects of SRT on trihalomethane
      (THM) formation in chlorinated PAC/MBR effluents, characteristics and THM
      formation reactivity of effluent dissolved organic matter (EfOM) at different
      SRTs were examined. PAC/MBR-180 had higher level of EfOM, which contained less
      simple aromatic proteins and exhibited lower specific UV absorbance. EfOM with
      molecular weight <5 kDa from PAC/MBR-30 (23%) was lower than PAC/MBR-180 (26%).
      About 50% of EfOM from PAC/MBR-30 was hydrophobic acids, which was higher than
      that from PAC/MBR-180 (about 36%). EfOM at SRT 180 days exhibited higher
      hydrophilicity. Prolonging SRT greatly reduced THM formation reactivity of EfOM,
      but increased the formation of bromine-containing species during chlorination of
      PAC/MBR effluents.

PMID- 24929810
TI  - Comparison of membrane foulants occurred under different sub-critical flux
      conditions in a membrane bioreactor (MBR).
AB  - Membrane fouling precludes the widespread application of membrane filtration
      system from treating wastewater and drinking water, and occurs even under sub
      critical flux operations. Hence the characteristics and behavior of membrane
      foulants should be thoroughly investigated, so as to find ways to reduce membrane
      fouling in membrane bioreactors. The purpose of this study is to compare the
      membrane fouling potential at different sub-critical flux operations and for
      different hydrophobic/hydrophilic membranes, and to investigate the vertical
      distribution of membrane foulants in a cake layer. Results showed that higher
      fouling propensity which occurred under 80% of critical flux of hydrophilic
      membrane was associated with the soluble fraction of proteins and
      polysaccharides, compared with 60% of critical flux. The cell-bound components
      were dominant under hydrophobic membrane operation. The highest concentration of
      proteins and polysaccharides was found between 40% and 80% of the depth of the
      cake layer. 

PMID- 24929811
TI  - Effect of dilute acid pretreatment severity on the bioconversion efficiency of
      Phalaris aquatica L. lignocellulosic biomass into fermentable sugars.
AB  - The effect of dilute acid pretreatment severity on the bioconversion efficiency
      of Phalaris aquatica lignocellulosic biomass into fermentable sugar monomers was
      studied. The pretreatment conditions were expressed in a combined severity factor
      (CSF), ranged from 0.13 to 1.16. The concentration of xylose and total monomeric
      sugars released from hemicellulose increased with pretreatment as the CSF
      increased. Dilute acid pretreatment resulted in about 1.7-fold increase in
      glucose release relative to the untreated biomass, while CSF was positively
      correlated with glucose recovery. A maximum glucose yield of 85.05% was observed
      at high severity values (i.e. CSF 1.16) after 72 h. The total amount of sugars
      released (i.e. xylose and glucose) was increased with pretreatment severity and a
      maximum conversion efficiency of 76.1% of structural carbohydrates was obtained
      at a CSF=1. Our data indicated that Phalaris aquatica L. is an alternative
      bioethanol feedstock and that hemicellulose removal promotes glucose yield.

PMID- 24929812
TI  - Steam explosion pretreatment for enhancing biogas production of late harvested
      hay.
AB  - Grasslands are often abandoned due to lack of profitability. Extensively
      cultivating grassland for utilization in a biogas-based biorefinery concept could
      mend this problem. Efficient bioconversion of this lignocellulosic biomass
      requires a pretreatment step. In this study the effect of different steam
      explosion conditions on hay digestibility have been investigated. Increasing
      severity in the pretreatment induced degradation of the hemicellulose, which at
      the same time led to the production of inhibitors and formation of pseudo-lignin.
      Enzymatic hydrolysis showed that the maximum glucose yields were obtained under
      pretreatment at 220  degrees C for 15 min, while higher xylose yields were
      obtained at 175  degrees C for 10 min. Pretreatment of hay by steam explosion
      enhanced 15.9% the methane yield in comparison to the untreated hay. Results
      indicate that hay can be effectively converted to methane after steam explosion
      pretreatment.

PMID- 24929813
TI  - Combining the effects of pulping severity and alkali concentration to optimize
      the lignocellulose-based AlkaPolP biorefinery concept.
AB  - Within the framework of the development of a novel lignocellulose biorefinery
      concept alkaline polyol pulping (AlkaPolP) of Pinus sylvestris was performed at
      different alkali concentrations. The obtained experimental data were used to
      develop simple mathematical models that allow the prediction of product yields
      and properties in dependence on a single parameter combining the effects of time,
      temperature and catalyst concentration. For this purpose the usual approach
      expressing the pulping severity R0 had to be complemented by the alkali
      concentration resulting in a modified severity factor R0('). The found regression
      models in the form of functions f(R0(')) can be used as a tool for the
      identification of those pulping conditions giving the desired product
      characteristics. Because the yields of the biorefinery products reach their
      maxima at different pulping conditions the optimization of the whole process
      turned out to be a multi-objective optimization problem.

PMID- 24929814
TI  - Molecular dynamics study on conformational differences between dGMP and 8-oxo
      dGMP: Effects of metal ions.
AB  - The modified nucleotide base 7,8-dihydro-8-oxo-guanine (8-oxo-G) is one of the
      major sources of spontaneous mutagenesis. Nucleotide-sanitizing enzymes, such as
      the MutT homolog-1 (MTH1) and nudix-type motif 5 (NUDT5), selectively remove 8
      oxo-G from the cellular pool of nucleotides. Previous studies showed that,
      although the syn conformation generally predominates in purine nucleotides with a
      bulky substituent at the 8-position, 8-oxo-dGMP binds to both MTH1 and NUDT5 in
      the anti conformation. This study was initiated to investigate the possibility
      that 8-oxo-dGMP itself may adopt the anti conformation. Molecular dynamics
      simulations of mononucleotides (dGMP, 8-oxo-dGMP) in aqueous solution were
      performed. 8-oxo-dGMP adopted the anti conformation as well as the syn
      conformation, and the proportion of adopting the anti conformation increased in
      the presence of metal ions. When 8-oxo-dGMP was in the anti conformation, a metal
      ion was located between the oxygen atom of phosphate and the oxygen atom at the 8
      position of 8-oxo-G. The types of stable anti conformations of 8-oxo-dGMP
      differed, depending on the ionic radii and charges of coexisting ions. These data
      suggested a role for metal ions, other than as cofactors for the hydrolysis of
      the di- and tri-phosphate forms of mononucleotides; that the metal ions help
      retain the anti conformation of the N-glycosidic torsion angle of 8-oxo-dGMP to
      promote the binding between the 8-oxo-G deoxynucleotide and the nucleotide
      sanitizing enzymes. 

PMID- 24929815
TI  - Computational determination of binding structures and free energies of glucose 6
      phosphate dehydrogenase with novel steroid inhibitors.
AB  - Glucose 6-phosphate dehydrogenase (G6PD), the first and the rate-limiting enzyme
      in the pentose phosphate pathway (PPP), catalyzes the oxidation of G6P to 6
      phosphogluconolactone and the reduction of NADP(+) to NADPH. Its key role in
      cancer promotes the development of a potent and selective inhibitor that might
      increase cancer cell death when combined with radiotherapy. In the present study,
      we investigated the detailed binding modes and binding free energies for G6PD
      interacting with a promising series of recently developed inhibitors, i.e., the
      steroid derivatives, by performing molecular docking, molecular dynamics (MD)
      simulations, and binding free energy calculations. The docking indicates that the
      inhibitors occupy the binding sites of both G6P and NADP(+). The calculated
      binding free energies on the basis of the MD-simulated enzyme-inhibitor complexes
      are in good agreement with the experimental activity data for all of the examined
      inhibitors. The valuable insights into the detailed enzyme-inhibitor binding
      including the important intermolecular interactions, e.g., the hydrogen bond
      interaction and the hydrophobic interaction, have been provided. The
      computational results provide new insights into future rational design of more
      potent inhibitors of G6PD as a treatment for cancer. 

PMID- 24929816
TI  - Stereoelectronic explanations for the mechanistic details of transimination and
      HF elimination reactions.
AB  - The beta-fluoroamines are commonly used as substrate analogs to determine the
      mechanistic details of enzymatic reactions. Presence of fluorine atom gives rise
      to the alterations in the electronic profile and the pKa of molecules which
      results in mechanistic deviations. The fluorine-substituted mechanism-based
      substrate analogs are widely used in the inactivation of pyridoxal 5'-phosphate
      (PLP)-dependent enzymes. The presence of fluorine atom also alters the sequence
      of reactions taking place in PLP-dependent enzymes where the HF elimination
      reaction appears in between the transimination and inactivation reactions.
      Despite the amount of the works on beta-fluoroamines, the effect of
      stereoelectronic differences on the transimination and HF elimination reactions
      taking place in PLP-dependent enzymes has not been investigated yet. A density
      functional theory study is conducted to elucidate mechanistic details of the
      reactions occurring in PLP-dependent enzymes. In order to understand the
      mechanistic insights of different isomers and the effect of the fluorine atom, 4
      amino-3-fluorobutanoic acid (3-F-GABA) enantiomers are chosen to be investigated
      besides 4-aminobutanoic acid (GABA), which is the natural substrate for gamma
      aminobutyric acid aminotransferase (GABA-AT). The investigated beta-fluoroamines
      are the experimentally proposed potential inhibitors of PLP-dependent enzyme GABA
      AT. 

PMID- 24929817
TI  - Survival, prophage induction, and invasive properties of lysogenic Salmonella
      Typhimurium exposed to simulated gastrointestinal conditions.
AB  - This study was designed to evaluate the viability, prophage induction, invasive
      ability, and relative gene expression in lysogenic Salmonella Typhimurium exposed
      to the simulated gastric juice (SGJ) at pH 2 (SGJ-2), 3 (SGJ-3), 4 (SGJ-4), and 5
      (SGJ-5) for 30 min followed by 0.5 % bile salts for 2 h. The susceptibility of
      lysogenic S. Typhimurium increased with decreasing pH value and increasing bile
      salt concentration. The lysogenic S. Typhimurium cells were least susceptible to
      SGJ-4 and SGJ-5, showing <1 log reduction. The highest prophage induction was
      observed by 3.34 log PFU/ml in lysogenic S. Typhimurium at SGJ-3 in the presence
      of 0.5 % bile salts. The numbers of invading lysogenic S. Typhimurium treated at
      SGJ-3, SGJ-4, and SGJ-5 were 3.57, 3.73, and 4.15 log CFU/cm(2), respectively.
      Most genes (hilA, hilC, hilD, invA, invE, invF, and sirA) were down-regulated in
      lysogenic S. Typhimurium treated at SGJ-3, SGJ-4, and SGJ-5. This study provides
      useful information for understanding physiological changes of lysogenic S.
      Typhimurium in the simulated gastrointestinal conditions. 

PMID- 24929818
TI  - Identification of a gene signature of a pre-transformation process by senescence
      evasion in normal human epidermal keratinocytes.
AB  - BACKGROUND: Epidemiological data show that the incidence of carcinomas in humans
      is highly dependent on age. However, the initial steps of the age-related
      molecular oncogenic processes by which the switch towards the neoplastic state
      occurs remain poorly understood, mostly due to the absence of powerful models. In
      a previous study, we showed that normal human epidermal keratinocytes (NHEKs)
      spontaneously and systematically escape from senescence to give rise to pre
      neoplastic emerging cells. METHODS: Here, this model was used to analyze the gene
      expression profile associated with the early steps of age-related cell
      transformation. We compared the gene expression profiles of growing or senescent
      NHEKs to post-senescent emerging cells. Data analyses were performed by using the
      linear modeling features of the limma package, resulting in a two-sided t test or
      F-test based on moderated statistics. The p-values were adjusted for multiple
      testing by controlling the false discovery rate according to Benjamini Hochberg
      method.The common gene set resulting of differential gene expression profiles
      from these two comparisons revealed a post-senescence neoplastic emergence (PSNE)
      gene signature of 286 genes. RESULTS: About half of these genes were already
      reported as involved in cancer or premalignant skin diseases. However,
      bioinformatics analyses did not highlight inside this signature canonical cancer
      pathways but metabolic pathways, including in first line the metabolism of
      xenobiotics by cytochrome P450. In order to validate the relevance of this
      signature as a signature of pretransformation by senescence evasion, we
      invalidated two components of the metabolism of xenobiotics by cytochrome P450,
      AKR1C2 and AKR1C3. When performed at the beginning of the senescence plateau,
      this invalidation did not alter the senescent state itself but significantly
      decreased the frequency of PSNE. Conversely, overexpression of AKR1C2 but not
      AKR1C3 increased the frequency of PSNE. CONCLUSIONS: To our knowledge, this study
      is the first to identify reprogrammation of metabolic pathways in normal
      keratinocytes as a potential determinant of the switch from senescence to pre
      transformation.

PMID- 24929819
TI  - Association between HMW adiponectin, HMW-total adiponectin ratio and early-onset
      coronary artery disease in Chinese population.
AB  - OBJECTIVE: Adiponectin is an adipose-secreting protein that shows
      atheroprotective property and has inverse relation with coronary artery disease
      (CAD). High-molecular weight (HMW) adiponectin is reported as the active form of
      adiponectin. In the present study, we aimed to investigate the association
      between total adiponectin, HMW adiponectin, HMW-total adiponectin ratio and the
      severity of coronary atherosclerosis, and to compare their evaluative power for
      the risk of CAD. METHODS: Serum levels of total and HMW adiponectin were measured
      in 382 early-onset CAD (EOCAD) patients and 305 matched controls undergoing
      coronary angiography by enzyme-linked immunosorbent assay (ELISA). Gensini score
      was used to evaluate the severity of coronary atherosclerosis. RESULTS: CAD onset
      age was positively correlated with HMW adiponectin (r = 0.383, P < 0.001) and HMW
      total adiponectin ratio (r = 0.429, P < 0.001) in EOCAD patients. Total and HMW
      adiponectin and HMW-total adiponectin ratio were all inversely correlated with
      Gensini score (r = -0.417, r = -0.637, r = -0.578, respectively; all P < 0.001).
      Multivariate binary logistic regression analysis demonstrated that HMW
      adiponectin and HMW-total adiponectin ratio were both inversely correlated with
      the risk of CAD (P < 0.05). ROC analysis indicated that areas under the ROC
      curves of HMW adiponectin and HMW-total adiponectin ratio were larger than that
      of total adiponectin (P < 0.05). CONCLUSIONS: Adiponectin is cardioprotective
      against coronary atherosclerosis onset in EOCAD patients. HMW adiponectin and HMW
      total adiponectin ratio show stronger negative associations with the severity of
      coronary atherosclerosis than total adiponectin does. HMW adiponectin and HMW
      total adiponectin ratio are effective biomarkers for the risk of CAD in Chinese
      population.

PMID- 24929821
TI  - Long-term chronic diseases and crash responsibility: a record linkage study.
AB  - OBJECTIVE: To assess the population impact of chronic conditions on the risk of
      road traffic crashes. METHODS: Data from three French national databases were
      extracted and matched: the national health care insurance database, police
      reports and the national police database of injurious crashes. Exposure to
      chronic conditions were compared between responsible and nonresponsible drivers.
      Analysis was performed using the Lasso (least absolute shrinkage and selection
      operator) method. RESULTS: 69,630 drivers involved in an injurious crash in
      France between 2005 and 2008, were included. 6210 (8.9%) were suffering from at
      least one long-term disease. When adjusted for prescription of medicines, blood
      alcohol, demographic driver characteristics and crash characteristics, increased
      risk of being responsible for a crash was found in drivers registered in the
      French healthcare database with the following long-term diseases: epilepsy (odds
      ratio [OR]=2.53 [1.53-4.20]), type 1 diabetes (OR=1.47) [1.12-1.92], alcoholic
      liver disease (OR=3.37 [1.40-8.13]), asthma (OR=1.72 [1.13-2.60]) and specific
      personality disorders (OR=1.35 [1.05-1.74]). No association was found for
      cardiovascular diseases or Alzheimer's disease. CONCLUSION: The results update
      the list of medical conditions that may impair driving skills. However, results
      should be considered cautiously with regards to potential regulatory driving
      judgments that could have a negative impact on patients' social life.

PMID- 24929820
TI  - Potential pathological roles for oxidized low-density lipoprotein and scavenger
      receptors SR-AI, CD36, and LOX-1 in aortic valve stenosis.
AB  - OBJECTIVE: To clarify the potential mechanisms by which oxidized low-density
      lipoprotein (oxLDL) could contribute to the progression of aortic valve stenosis
      (AVS). METHODS: We investigated a total of 46 stenotic and 20 control human
      aortic valves. The mRNA expression levels of scavenger receptor class A type 1
      (SR-A1), CD36, Lectin-like oxidized LDL receptor-1 (LOX-1), and scavenger
      receptor class B type 1 (SR-B1) were studied using qPCR. Their cellular
      distribution in the valves was assessed by immunohistochemistry, and the
      potential effects of oxLDL were studied in cultured myofibroblasts isolated from
      the aortic valves. RESULTS: In AVS, the proinflammatory SR-A1 and the angiogenic
      LOX-1 were upregulated (p = 0.003 and p = 0.002), whereas the antiangiogenic CD36
      was downregulated (p = 0.02). The expression of the atheroprotective SR-B1
      remained unchanged. Immunohistochemistry revealed that SR-A1 was expressed by
      macrophages, whereas the expression of CD36 and LOX-1 was confined to
      myofibroblasts and endothelial cells in the diseased valves. In cultured valvular
      myofibroblasts, mast cell-derived components and TNF-alpha induced LOX-1
      expression (p = 0.05 and p < 0.001), whereas oxLDL promoted the expression of
      proinflammatory cytokines. Furthermore, the expression of osteoprotegerin, an
      inhibitor of valvular calcification, decreased in response to oxLDL. Finally,
      myofibroblasts derived from stenotic valves accumulated more DiI-labeled oxLDL
      than myofibroblasts derived from macroscopically healthy valves (p = 0.035), so
      revealing enhanced foam cell-forming potential of myofibroblasts in the diseased
      valves. CONCLUSION: This study unveils the presence of SR-A1, CD36, and LOX-1 in
      aortic valves and suggests potential mechanisms by which they may contribute to
      the pathological angiogenesis, inflammation, calcification, and lipid
      accumulation in AVS.

PMID- 24929822
TI  - Microsimulation modelling of driver behaviour towards alternative warning devices
      at railway level crossings.
AB  - Level crossings are amongst the most complex of road safety issues, due to the
      addition of rail infrastructure, trains and train operations. The differences in
      the operational characteristics of different warning devices together with
      varying crossing, traffic or/and train characteristics, cause different driver
      behaviour at crossings. This paper compares driver behaviour towards two novel
      warning devices (rumble strips and in-vehicle audio warning) with two
      conventional warning devices (flashing light and stop sign) at railway level
      crossings using microsimulation modelling. Two safety performance indicators
      directly related to collision risks, violation and time-to-collision, were
      adopted. Results indicated the active systems were more effective at reducing
      likely collisions compared to passive devices. With the combined application of
      driving simulation and traffic microsimulation modelling, traffic safety
      performance indicators for a level crossing can be estimated. From these,
      relative safety comparisons for the different traffic devices are derived, or
      even for absolute safety evaluation with proper calibration from field
      investigations. 

PMID- 24929823
TI  - Managing children's risk of injury in the home: does parental teaching about home
      safety reduce young children's hazard interactions?
AB  - Past research confirms that parents extend much effort to teach their young
      children about safety, but little is known about this process. The present study
      examined mothers' use of teaching as a strategy to manage young children's risk
      of home injury and how this impacts children's hazard interactions. Mothers of
      three-year-olds completed an in-home room-by-room interview in which they
      identified injury hazards that concern them, reported on use of teaching to
      manage risk of injury from these hazards, rated children's understanding of these
      safety issues and compliance with behavioral guidelines regarding these safety
      issues, and reported on children's recent interactions with these hazards. They
      also completed questionnaire measures of how difficult the child is to manage and
      the child's typical level of risk taking. Results revealed that children's
      understanding of safety impacted both their compliance and hazard interactions,
      moderating the impact of risk taking on compliance and also the impact of
      children's difficult-to-manage score on hazard interactions. These findings
      demonstrate that teaching strategies need to effectively enhance children's
      understanding of the safety issue in order to reduce children's risk of hazard
      interactions. 

PMID- 24929824
TI  - Enhancements in peer review of manuscripts by the Journal.

PMID- 24929825
TI  - The role of intraocular video endoscopic fundal examination before
      keratoprosthesis surgery.

PMID- 24929826
TI  - Reply: To PMID 24075422.

PMID- 24929827
TI  - Macular ganglion cell/inner plexiform layer measurements by spectral domain
      optical coherence tomography for detection of early glaucoma and comparison to
      retinal nerve fiber layer measurements.

PMID- 24929829
TI  - Genome and transcriptome of the porcine whipworm Trichuris suis.
AB  - Trichuris (whipworm) infects 1 billion people worldwide and causes a disease
      (trichuriasis) that results in major socioeconomic losses in both humans and
      pigs. Trichuriasis relates to an inflammation of the large intestine manifested
      in bloody diarrhea, and chronic disease can cause malnourishment and stunting in
      children. Paradoxically, Trichuris of pigs has shown substantial promise as a
      treatment for human autoimmune disorders, including inflammatory bowel disease
      (IBD) and multiple sclerosis. Here we report whole-genome sequencing at ~140-fold
      coverage of adult male and female T. suis and ~80-Mb draft assemblies. We explore
      stage-, sex- and tissue-specific transcription of mRNAs and small noncoding RNAs.

PMID- 24929831
TI  - Developmental patterning by gradients of mobile small RNAs.
AB  - Development of multicellular organisms depends on intercellular communication via
      mobile signals that provide positional information to coordinate cell fate
      decisions. In addition to peptide ligands, transcription factors, and hormones,
      plants use small RNAs as positional instructive signals. The unique patterning
      properties of small RNA gradients resulting from regulated mobility suggest
      conceptual similarities to the function of animal morphogens, and provide
      robustness and precision to the formation of cell fate boundaries. While common
      principles may underlie the formation, stability, and interpretation of both
      plant small RNA and animal morphogen gradients, the unique nature of small RNAs
      with respect to their biogenesis and target regulation imply important
      differences as well. In this review, we discuss the patterning properties of
      mobile small RNAs and highlight recent studies that have advanced our
      understanding of how small RNAs move, and how the graded accumulation that
      underlies their patterning activity could be created, maintained, and
      interpreted. 

PMID- 24929830
TI  - Whipworm genome and dual-species transcriptome analyses provide molecular
      insights into an intimate host-parasite interaction.
AB  - Whipworms are common soil-transmitted helminths that cause debilitating chronic
      infections in man. These nematodes are only distantly related to Caenorhabditis
      elegans and have evolved to occupy an unusual niche, tunneling through epithelial
      cells of the large intestine. We report here the whole-genome sequences of the
      human-infective Trichuris trichiura and the mouse laboratory model Trichuris
      muris. On the basis of whole-transcriptome analyses, we identify many genes that
      are expressed in a sex- or life stage-specific manner and characterize the
      transcriptional landscape of a morphological region with unique biological
      adaptations, namely, bacillary band and stichosome, found only in whipworms and
      related parasites. Using RNA sequencing data from whipworm-infected mice, we
      describe the regulated T helper 1 (TH1)-like immune response of the chronically
      infected cecum in unprecedented detail. In silico screening identified numerous
      new potential drug targets against trichuriasis. Together, these genomes and
      associated functional data elucidate key aspects of the molecular host-parasite
      interactions that define chronic whipworm infection. 

PMID- 24929832
TI  - Quality of life, alcohol detoxification and relapse: is quality of life a
      predictor of relapse or only a secondary outcome measure?
AB  - PURPOSE: To estimate variations in Overall Quality Of Life (OQOL) within 12
      months following alcohol detoxification and to evaluate the predictive value of
      OQOL for relapse and alcohol use severity. METHODS: Alcohol use disorders and
      four OQOL domains (physical health, psychological health, social relationships
      and environment) were assessed in 199 patients entering in-patient alcohol
      detoxification. Follow-up assessments were performed at 6 and 12 months after
      discharge. Cross-sectional and longitudinal analyses explored the relationship
      between OQOL and alcohol use severity, examining differences between abstinent
      and relapsed patients. The predictive value of OQOL was analyzed by logistic and
      linear regression. RESULTS: Correlation between OQOL and Alcohol Use Disorders
      Identification Test scores was confirmed at all stages of observation. Abstinent
      patients showed a significant improvement in all OQOL domains at 6 months after
      discharge, whereas OQOL domains did not undergo any significant change in
      relapsed patients. Baseline OQOL did not prove to be predictive of either relapse
      or alcohol use severity. CONCLUSIONS: Overall quality of life changed in parallel
      with alcohol use severity throughout the duration of the study, confirming it to
      be a useful and sensitive measure of secondary outcome for alcohol
      detoxification. Conversely, none of the OQOL baseline scores functioned as
      predictors of relapse within 12 months following discharge or alcohol use
      severity in relapsed patients.

PMID- 24929828
TI  - Genome-wide association analysis identifies six new loci associated with forced
      vital capacity.
AB  - Forced vital capacity (FVC), a spirometric measure of pulmonary function,
      reflects lung volume and is used to diagnose and monitor lung diseases. We
      performed genome-wide association study meta-analysis of FVC in 52,253
      individuals from 26 studies and followed up the top associations in 32,917
      additional individuals of European ancestry. We found six new regions associated
      at genome-wide significance (P < 5 * 10(-8)) with FVC in or near EFEMP1, BMP6,
      MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with
      spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated
      regions were followed up in samples from African-American, Korean, Chinese and
      Hispanic individuals. We detected transcripts for all six newly implicated genes
      in human lung tissue. The new loci may inform mechanisms involved in lung
      development and the pathogenesis of restrictive lung disease. 

PMID- 24929833
TI  - Rates and predictors of adherence to psychotropic medications in children with
      autism spectrum disorders.
AB  - Medication adherence in children is poor, particularly among those with chronic
      or mental health disorders. However, adherence has not been fully assessed in
      autism spectrum disorders (ASDs). The validated proportion of days covered method
      was used to quantify adherence to psychotropic medication in Medicaid-eligible
      children who met diagnostic criteria for ASD between 2000 and 2008 (N = 628).
      Among children prescribed attention deficit hyperactivity disorder (ADHD)
      medications, antidepressants, or antipsychotics, 44, 40 and 52 % were adherent
      respectively. Aggressive behaviors and abnormalities in eating, drinking, and/or
      sleeping, co-occurring ADHD, and the Medication Regimen Complexity Index were the
      most significant predictors of adherence rather than demographics or core
      deficits of ASD. Identifying barriers to adherence in ASD may ultimately lead to
      improved treatment outcomes.

PMID- 24929834
TI  - Factors shaping initial decision-making to self-test amongst cohabiting couples
      in urban Blantyre, Malawi.
AB  - In sub-Saharan Africa, most new HIV infections occur in stable relationships,
      making couples testing an important intervention for HIV prevention. We explored
      factors shaping the decision-making of cohabiting couples who opted to self-test
      in Blantyre, Malawi. Thirty-four self-tested participants (17 couples) were
      interviewed. Motivators for HIV self-testing (HIVST) emerged at three main
      levels. Individual motivations included perceived benefits of access to
      treatment, and self-checking of serostatus in the hope of having been cured by
      prolonged treatment or faith-healing. HIVST was considered convenient,
      confidential, reassuring and an enabling new way to test with one's partner.
      Partnership motivations included both positive (mutual encouragement) and
      negative (suspected infidelity) aspects. For women, long-term health and
      togetherness were important goals that reinforced motivations for couples
      testing, whereas men often needed persuasion despite finding HIVST more flexible
      and less onerous than facility-based testing. Internal conflict prompted some
      partners to use HIVST as a way of disclosing their previously concealed HIV
      positive serostatus. Thus, the implementation of community-based HIVST should
      acknowledge and appropriately respond to decision-making processes within
      couples, which are shaped by gender roles and relationship dynamics. 

PMID- 24929835
TI  - Parameters of infection in replacement and voluntary donors in the western part
      of Turkey.
AB  - BACKGROUND: According to our center's experiences familial/replacement donors
      (FRDs) frequently donate blood for the first time in their lives. Therefore,
      results of infection parameters are expected to be different voluntary donors
      (VDs), at similar rates to the population. The present study aimed to investigate
      if there were any difference in VDs and FRDs in terms of infection parameters.
      OBJECTIVE: The blood donation records over 6 years (2004-2010) were reviewed,
      retrospectively. HBsAg, anti-HCV, anti-HIV screening tests were performed by
      ELISA and syphilis screening was performed by the RPR method. MATERIAL AND
      METHODS: Out of 71.217, 16.727 donors donated whole blood as FRD. Among the whole
      blood donated by FRD, the positives for HBsAg, anti-HCV and RPR were 1.23%,
      0.37%, and 0.07%, respectively. Confirmed anti-HIV screening test was not
      observed in this group. Positivities for HBsAg, anti-HCV, anti-HIV and RPR in VD
      were 1.36%, 0.42%, 0.004%, and 0.04%, respectively. RESULTS: When FRD and VD were
      analyzed statistically, HBsAg rates were significantly higher among FRD in the
      years 2004, 2007 and 2008, whereas they were significantly high among VD in year
      2005. HBsAg rates stated in the years 2006-2009 were insignificant. Significantly
      high results were observed in HCV rates in the year 2005 among VD, whereas
      insignificant levels were observed in other years. HIV rates were insignificant
      among VD in the years 2004 and 2005, confirmed positivity was established in only
      one patient. Values in all years in RPR rates were statistically insignificant.
      Grouping donors as replacement and voluntary has no importance in infection
      parameters. CONCLUSION: Grouping donors as replacement and voluntary has no
      importance in infection parameters. Appropriate donor inquiries and screening of
      infection parameters by reliable proven tests preserve their significances.

PMID- 24929836
TI  - Frequencies of Duffy blood group alleles in Northern Pakistani donors.
AB  - OBJECTIVE: Find the allele frequencies of Duffy blood group antigens in donor
      population from northern Pakistan. DESIGN: Cross sectional study. PLACE AND
      DURATION OF STUDY: Armed Forces Institute of Transfusion (AFIT), Rawalpindi in
      year 2012. PATIENTS AND METHODS: A total of 1000 healthy, adult blood donors were
      included in the study. Blood samples were collected in ethylenediamine tetra
      aceticacid (EDTA) tube and then tested with anti sera Fy(a) and Fy(b) by the tube
      method. RESULTS: The allele frequencies of Duffy blood group antigens were
      calculated. The most common phenotype was Fy(a+b+) which was present in 552
      (55.2%) donors followed by the Fy(a+b-) phenotype in 228 (22.8%) donors, while
      178 (17.8%) were Fy(a-b+) and the least prevalent phenotype was Fy(a-b-) which
      was present in 42 (4.2%) of donors. CONCLUSION: The majority of our population is
      heterozygous for Duffy antigens a and b.

PMID- 24929837
TI  - A comprehensive study of ovine haemostasis to assess suitability to model human
      coagulation.
AB  - INTRODUCTION: Similarities in size, anatomy and physiology have supported the use
      of sheep to model a wide range of human diseases, including coagulopathy.
      However, coagulation studies involving sheep are limited by the absence of high
      quality data defining normal ovine coagulation and fibrinolysis. MATERIALS AND
      METHODS: Full blood examination, routine and specialised coagulation tests,
      rotational thromboelastometry and whole blood platelet aggregometry was performed
      on 50 healthy Samm & Border Leicester Cross ewes and compared to corresponding
      human ranges. Intraspecies breed and gender variability was investigated by
      comparison to a smaller population of 13 healthy Merino wethers. RESULTS: Ovine
      coagulation was similar to human according to routine coagulation methods (PT,
      aPTT, TCT, Fib(C)) and some specialised coagulation tests (vWF, AT, Plasmin Inh).
      Despite these similarities, ovine secondary haemostasis demonstrated substantial
      differences to that of human. Rapid initiation of the contact activation pathway,
      high levels of FVIII, low Protein C, greater overall clot firmness and a reduced
      capacity for clot lysis was documented in sheep. In addition, ADP and collagen
      agonists precipitated a reduced primary haemostatic response in sheep relative to
      human. Intraspecies differences in whole blood platelet aggregometry between the
      cohorts of sheep indicate the need for breed-specific normal ranges. CONCLUSIONS:
      The application of a board spectrum of coagulation assays has enabled elucidation
      of the similarities as well as differences between ovine and human coagulation.
      The new knowledge generated from this study will guide the design of future
      translational coagulation studies in ovine models.

PMID- 24929838
TI  - Predictors of attempted inferior vena cava filters retrieval in a tertiary care
      centre.
AB  - BACKGROUND: Retrieval rates of optional recovery inferior vena cava (IVC) filters
      in US hospitals range from 11 - 70%. We conducted a retrospective study in a
      Canadian tertiary care centre to determine retrieval rates and predictors of
      filter removal. METHODS: Consecutive patients who had a retrievable IVC filter
      inserted or removed between January 2007 and December 2010 were identified. Data
      collected included baseline demographics, indications for filter insertion and
      removal, documentation of an IVC filter management plan, reasons for non
      retrieval, complications, and death. RESULTS: 275 patients with a median age of
      60years were followed in hospital for a median of 17 patient-days (range 1-876).
      Indications for filter placement were acute or prior VTE with contraindication to
      anticoagulation (72.4%), high risk of PE (11.3%) and primary prophylaxis (13.8%).
      Retrieval was attempted in 165 patients (60%) and was successful in 146 patients
      (53.1%). The most common reason for failed retrieval was filter thrombus.
      Predictors of attempted retrieval included documentation of filter plan (odds
      ratio [OR] 16.7; p<0.001), surgical indication for IVC filter insertion (OR 4.8;
      p=0.002), age <=70years (OR 3.8; p=0.001), Hematology service involvement (OR
      3.0; p=0.006), and presence of metastatic cancer (OR 0.2; p=0.001). Thrombotic
      complications occurred in 48 patients, including 3 patients who died of fatal PE.
      CONCLUSION: Our filter retrieval rate is suboptimal. Improvements in follow-up
      documentation or a dedicated clinical service may help increase retrieval rates.

PMID- 24929839
TI  - Effect of resection of localized pancreaticobiliary adenocarcinoma on angiogenic
      markers and tissue factor related pro-thrombotic and pro-angiogenic activity.
AB  - In this study, 52 patients were studied to elucidate the relative impact of
      resection of localized pancreaticobiliary adenocarcinoma (PBC) on circulating
      factors of tumour-associated angiogenesis e.g. tissue factor bearing
      microparticles (TFMP) and vascular endothelial growth factor (VEGF) and their
      clinicopathological significance to angiogenesis markers in cancer tissue from
      PBC patients. Angiogenesis array analysis on serum samples revealed that surgical
      resection of tumour lesion in PBC patients affects the levels of a panel of
      angiogenesis-related molecules, including VEGF that was verified by ELISA to
      significantly reduce (median & IQR: 1003(369-2000) vs. 457(159-834) pg/ml;
      p<0.05). Correspondingly, a significant decrease in the angiogenic activity
      (decreased capillary tube formation; p<0.05) of serum samples after the surgery
      was also found. Despite a decrease in number of circulating TFMP after surgery,
      this did not reach statistical significance; there was a significant reduction in
      pro-coagulant activity (prolonged prothrombin time, p<0.001) post-operatively. In
      addition, the activity of total microparticles (MP activity assay, p<0.05) was
      decreased significantly. Immunohistochemical staining of tumour tissue revealed a
      strong correlation between the microvessel density (MVD) and VEGF expression.
      Also, higher levels of circulating TFMP or TF related activity (prothrombin time)
      correlated significantly with TF expression and MVD on tumour tissues from PBC
      patients. These findings suggest that in pancreaticobiliary adenocarcinoma TF
      related angiogenesis drivers are equally significant to VEGF ones, raising the
      clinical question of whether the effectiveness of angiogenesis targeting studies
      could be improved through the 'dual' targeting of these pathways in PBC. 

PMID- 24929840
TI  - The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in
      atrial fibrillation: the MAQI(2) experience.
AB  - INTRODUCTION: Guidelines recommend the assessment of stroke and bleeding risk
      before initiating warfarin anticoagulation in patients with atrial fibrillation.
      Many of the elements used to predict stroke also overlap with bleeding risk in
      atrial fibrillation patients and it is tempting to use stroke risk scores to
      efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding
      risk scores to predict bleeding has not been thoroughly assessed. METHODS: 2600
      patients followed at seven anticoagulation clinics were followed from October
      2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and
      ATRIA) were retrospectively applied to each patient. The primary outcome was the
      first major bleeding event. Area under the ROC curves were compared with C
      statistic and net reclassification improvement (NRI) analysis was performed.
      RESULTS: 110 patients experienced a major bleeding event in 2581.6 patient-years
      (4.5%/year). Mean follow up was 1.0+/-0.8years. All of the formal bleeding risk
      scores had a modest predictive value for first major bleeding events (C statistic
      0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic
      difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64%
      improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2
      VASc score, respectively. CONCLUSIONS: The CHADS2 and CHA2DS2-VASc scores did not
      perform as well as formal bleeding risk scores for prediction of major bleeding
      in non-valvular atrial fibrillation patients treated with warfarin. All three
      bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately
      well.

PMID- 24929841
TI  - Sebaceous epithelial-myoepithelial carcinoma of the parotid gland: a case report
      of a new histologic variant.
AB  - Epithelial-myoepithelial carcinoma (EMCa) is a double-cell layered low-grade
      malignant tumor, representing approximately 1% of all salivary gland tumors
      (Barnest et al. 2005 [1], Brocheriou et al. 1991 [2], Fonte et al. 2001 [3]). Its
      histologic characteristic is that of an inner layer of cuboidal epithelial cells
      with dense granular cytoplasm and central or basal rounded nucleus, and an outer
      layer of clear, polygonal myoepithelial cells, together forming ductal structures
      in a lobulated papillary or cystic pattern. Although solid components of clear
      cells are not uncommon, and squamous differentiation, spindle cells, and
      oncocytic appearance are well-documented histologic features of EMCa, sebaceous
      differentiation as a precise histologic variant has, to our knowledge, only been
      suggested by Shinozaki et al [4] in 2008. In this report, we present a case of a
      carcinoma of the parotid gland in a 59-year old female patient with an
      immunophenotype supporting the proposed entity of sebaceous EMCa. 

PMID- 24929843
TI  - Tufted titmouse (Baeolophus bicolor) calling and risk-sensitive foraging in the
      face of threat.
AB  - Individuals often produce alarm or mobbing calls when they detect a threat such
      as a predator. Little is known about whether such calling is affected by the
      facial orientation of a potential threat, however. We tested for an effect of
      facial orientation of a potential threat on tufted titmice, Baeolophus bicolor, a
      songbird that uses chick-a-dee calls in a variety of social contexts. In two
      studies, a human observer wore an animal mask that either faced or faced away
      from the focal bird(s). In Study 1, focal birds were individual titmice captured
      in a walk-in trap, and the observer stood near the trapped bird. In Study 2,
      focal birds were titmouse flocks utilizing a feeding station and the observer
      stood near the station. In both studies, calling behavior was affected by mask
      orientation. In Study 2, foraging and agonistic behavior were also affected.
      Titmice can therefore perceive the facial orientation of a potential threat, and
      this perception affects different behavioral systems, including calling. Our
      results indicate sensitivity of titmice to the facial orientation of a potential
      predator in two quite different motivational contexts. This work suggests the
      possibility of strategic signaling by prey species depending upon the perceptual
      space of a detected predator. 

PMID- 24929842
TI  - Chronic inflammation and the role for cofactors (hepatitis C, drug abuse,
      antiretroviral drug toxicity, aging) in HAND persistence.
AB  - HIV-associated neurocognitive disorders (HAND) is a group of syndromes of varying
      degrees of cognitive impairment affecting up to 50 % of HIV-infected individuals.
      The neuropathogenesis of HAND is thought to be driven by HIV invasion and
      productive replication within brain perivascular macrophages and endogenous
      microglia, and to some degree by restricted infection of astrocytes. The
      persistence of HAND in individuals experiencing suppression of systemic HIV viral
      load with antiretroviral therapy (ART) is incompletely explained, and suggested
      factors include chronic inflammation, persistent HIV replication in brain
      macrophages, effects of aging on brain vulnerability, and co-morbid conditions
      including hepatitis C (HCV) co-infection, substance abuse, and CNS toxicity of
      ART, among other factors. This review discusses several of these conditions:
      chronic inflammation, co-infection with HCV, drugs of abuse, aging, and
      antiretroviral drug effects. Effectively managing these co-morbid conditions in
      individuals with and without HAND is critical for improving neurocognitive
      outcomes and decreasing HIV-associated morbidity.

PMID- 24929844
TI  - An emerging population: the chronically critically ill.

PMID- 24929845
TI  - A little-known cause of chest pain in a 14-year-old athlete.

PMID- 24929846
TI  - Implementing an early childhood developmental screening and surveillance program
      in primary care settings: lessons learned from a project in Illinois.
AB  - Enhancing Developmentally Oriented Primary Care (EDOPC) is a project with a goal
      to increase the financing and delivery of preventive developmental services for
      children birth to age 3 years in the state of Illinois. Primary care providers
      have more opportunities to screen and observe infants and toddlers than any other
      professional, because they see them up to 13 times in the first 3 years of life
      for well-child visits. The project focused on using a 1-hour, on-site training
      for primary care providers and their entire office staff as the method of
      increasing knowledge, focusing on intent to change practice and implementation of
      routine early childhood developmental screening. Although many primary care
      providers routinely use only developmental surveillance in their practices,
      clinical practice guidelines recommend routine use of standardized developmental
      screening, using validated developmental screening tools. This article includes
      lessons learned and recommendations based on clinical practice guidelines and
      experiences of the team members during implementation of the EDOPC project.
      Primary care providers are critical to this process because children with
      developmental disorders have the best long-term outcomes and opportunities for
      improved family functioning with early detection, diagnosis, and treatment. 

PMID- 24929849
TI  - Postmenopausal physiological changes.
AB  - The hallmark of menopause is the marked reduction of estradiol levels due to
      ovarian failure. This, among other factors result in hot flashes, the most common
      menopausal symptom. Hot flashes (HFs) can be measured objectively, both inside
      and outside the laboratory, using sternal skin conductance, an electrical measure
      of sweating. We have found that HFs are triggered by small elevations in core
      body temperature (T C ), acting within a greatly reduced thermoneutral zone. This
      reduction is caused by elevated central sympathetic activation, among other
      factors. There is a circadian rhythm of HFs peaking at 1825 h. Imaging studies
      have shown that hot flash activation begins in the brainstem, followed by the
      insula and by the prefrontal cortex. HFs in the first, but not the second half of
      the night can produce awakenings and arousals. This is because rapid eye movement
      (REM) sleep suppresses thermoregulatory effector responses, which include hot
      flashes. 

PMID- 24929847
TI  - The role of microRNAs in lymphopoiesis.
AB  - The immune system is composed of a diverse range of cell types, each with a
      distinct function. It can be broadly divided into the lymphoid (T, B, NK, etc.)
      and myeloid (monocyte, granulocyte, etc.) arms. Lymphopoiesis, the development
      and differentiation of lymphoid lineages, has been studied extensively for
      decades. For example, the influence of extracellular signals, signaling pathways
      and transcription factors has already been well documented. However, the
      importance of microRNAs has been highlighted by a surge of studies in recent
      years. In this review, we will discuss what is currently known about the role of
      microRNAs in lymphopoiesis, from the hematopoietic stem cell through to the
      differentiation of mature lymphocytes including thymic development, helper and
      regulatory T cells, fate determination of B cells and dendritic cells. 

PMID- 24929848
TI  - Homing of cytokine-induced killer cells during the treatment of acute
      promyelocytic leukemia.
AB  - Cytokine-induced killer (CIK) cells have been shown to be an effective
      immunotherapy for malignancies. However, their clinical application has been
      limited due to lack of knowledge on their in vivo kinesis. In this study, we
      explored their biodistribution by labeling CIK cells with (18)F-FDG and tracking
      their in vivo migration by PET/CT imaging. In the nine refractory APL patients
      enrolled in this study, pre-treatment PET/CT scans revealed leukemia burdens in
      vertebrae, and the bones of the pelvis and limbs. Post-treatment serial PET/CT
      tracked the localization of CIK cells over time: at 1 h, the majority of these
      cells accumulated diffusely in the lungs, while the first minor cell activities
      were observed in brain, liver and spleen; at 4 and 8 h, they not only migrated to
      the heart, spleen, and liver, but also showed tendencies to accumulate in bone
      marrow and brain. This specific cell migration route suggested that CIK cells
      show in vivo functional kinesis and potency as a targeted immunotherapy. The
      clinical outcome of this small cohort of nine patients supported the efficacy of
      this regimen: two patients achieved rapid complete remission after three-cycle
      treatment, and six patients remained stable, subsequently became sensitive to
      conventional therapy, and also achieved complete remission.

PMID- 24929850
TI  - The complete type of pachydermoperiostosis: a novel nonsense mutation p.E141* of
      the SLCO2A1 gene.

PMID- 24929851
TI  - Insights into reference point indentation involving human cortical bone:
      sensitivity to tissue anisotropy and mechanical behavior.
AB  - Reference point indentation (RPI) is a microindentation technique involving 20
      cycles of loading in "force-control" that can directly assess a patient's bone
      tissue properties. Even though preliminary clinical studies indicate a capability
      for fracture discrimination, little is known about what mechanical behavior the
      various RPI properties characterize and how these properties relate to
      traditional mechanical properties of bone. To address this, the present study
      investigated the sensitivity of RPI properties to anatomical location and tissue
      organization as well as examined to what extent RPI measurements explain the
      intrinsic mechanical properties of human cortical bone. Multiple indents with a
      target force of 10N were done in 2 orthogonal directions (longitudinal and
      transverse) per quadrant (anterior, medial, posterior, and lateral) of the
      femoral mid-shaft acquired from 26 donors (25-101 years old). Additional RPI
      measurements were acquired for 3 orthogonal directions (medial only). Independent
      of age, most RPI properties did not vary among these locations, but they did
      exhibit transverse isotropy such that resistance to indentation is greater in the
      longitudinal (axial) direction than in the transverse direction (radial or
      circumferential). Next, beam specimens (~2mm*5mm*40mm) were extracted from the
      medial cortex of femoral mid-shafts, acquired from 34 donors (21-99 years old).
      After monotonically loading the specimens in three-point bending to failure, RPI
      properties were acquired from an adjacent region outside the span. Indent
      direction was orthogonal to the bending axis. A significant inverse relationship
      was found between resistance to indentation and the apparent-level mechanical
      properties. Indentation distance increase (IDI) and a linear combination of IDI
      and the loading slope, averaged over cycles 3 through 20, provided the best
      explanation of the variance in ultimate stress (r(2)=0.25, p=0.003) and toughness
      (r(2)=0.35, p=0.004), respectively. With a transverse isotropic behavior akin to
      tissue hardness and modulus as determined by micro- and nano-indentation and a
      significant association with toughness, RPI properties are likely influenced by
      both elastic and plastic behavior of bone tissue. 

PMID- 24929852
TI  - Diversity of mitochondria-dependent dilator mechanisms in vascular smooth muscle
      of cerebral arteries from normal and insulin-resistant rats.
AB  - Mitochondrial depolarization following ATP-sensitive potassium (mitoKATP) channel
      activation has been shown to induce cerebral vasodilation by generation of
      mitochondrial reactive oxygen species (ROS), which sequentially promotes
      frequency of calcium sparks and activation of large conductance calcium-activated
      potassium channels (BKCa) in vascular smooth muscle (VSM). We previously
      demonstrated that cerebrovascular insulin resistance accompanies aging and
      obesity. It is unclear whether mitochondrial depolarization without the ROS
      generation enhances calcium sparks and vasodilation in phenotypically normal
      [Sprague Dawley (SD); Zucker lean (ZL)] and insulin-resistant [Zucker obese (ZO)]
      rats. We compared the mechanisms underlying the vasodilation to ROS-dependent
      (diazoxide) and ROS-independent [BMS-191095 (BMS)] mitoKATP channel activators in
      normal and ZO rats. Arterial diameter studies from SD, ZL, and ZO rats showed
      that BMS as well as diazoxide induced vasodilation in endothelium-denuded
      cerebral arteries. In normal rats, BMS-induced vasodilation was mediated by
      mitochondrial depolarization and calcium sparks generation in VSM and was reduced
      by inhibition of BKCa channels. However, unlike diazoxide-induced vasodilation,
      scavenging of ROS had no effect on BMS-induced vasodilation. Electron spin
      resonance spectroscopy confirmed that diazoxide but not BMS promoted vascular ROS
      generation. BMS- as well as diazoxide-induced vasodilation, mitochondrial
      depolarization, and calcium spark generation were diminished in cerebral arteries
      from ZO rats. Thus pharmacological depolarization of VSM mitochondria by BMS
      promotes ROS-independent vasodilation via generation of calcium sparks and
      activation of BKCa channels. Diminished generation of calcium sparks and reduced
      vasodilation in ZO arteries in response to BMS and diazoxide provide new insights
      into mechanisms of cerebrovascular dysfunction in insulin resistance.

PMID- 24929853
TI  - Neural programming of mesenteric and renal arteries.
AB  - There is evidence for developmental origins of vascular dysfunction yet little
      understanding of maturation of vascular smooth muscle (VSM) of regional
      circulations. We measured maturational changes in expression of myosin
      phosphatase (MP) and the broader VSM gene program in relation to mesenteric small
      resistance artery (SRA) function. We then tested the role of the sympathetic
      nervous system (SNS) in programming of SRAs and used genetically engineered mice
      to define the role of MP isoforms in the functional maturation of the mesenteric
      circulation. Maturation of rat mesenteric SRAs as measured by qPCR and
      immunoblotting begins after the second postnatal week and is not complete until
      maturity. It is characterized by induction of markers of VSM differentiation
      (smMHC, gamma-, alpha-actin), CPI-17, an inhibitory subunit of MP and a key
      target of alpha-adrenergic vasoconstriction, alpha1-adrenergic, purinergic X1,
      and neuropeptide Y1 receptors of sympathetic signaling. Functional correlates
      include maturational increases in alpha-adrenergic-mediated force and calcium
      sensitization of force production (MP inhibition) measured in first-order
      mesenteric arteries ex vivo. The MP regulatory subunit Mypt1 E24+/LZ- isoform is
      specifically upregulated in SRAs during maturation. Conditional deletion of mouse
      Mypt1 E24 demonstrates that splicing of E24 causes the maturational reduction in
      sensitivity to cGMP-mediated vasorelaxation (MP activation). Neonatal chemical
      sympathectomy (6-hydroxydopamine) suppresses maturation of SRAs with minimal
      effect on a conduit artery. Mechanical denervation of the mature rat renal artery
      causes a reversion to the immature gene program. We conclude that the SNS
      captures control of the mesenteric circulation by programming maturation of the
      SRA smooth muscle.

PMID- 24929854
TI  - Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric
      resistance arteries.
AB  - In resistance arteries, a chronic increase in blood flow induces hypertrophic
      outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats
      aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we
      hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was
      increased in vivo in mesenteric resistance arteries after ligation of the side
      arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and
      normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter
      and cross-sectional area increased in HF arteries compared with NF arteries in 3
      mo-old male and female rats. In 12-mo-old rats, diameter increased only in female
      rats. Endothelial nitric oxide synthase expression and endothelium-mediated
      relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2
      phosphorylation, NADPH oxidase subunit expression levels, and arterial
      contractility to KCl and to phenylephrine were greater in HF vessels than in NF
      vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced
      a similar pattern with an increased contractility without diameter increase in HF
      arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with
      hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor
      blocker candesartan restored HF remodeling and normalized arterial contractility
      in HF vessels. Thus, we found that FMR of resistance arteries remains efficient
      in 12-mo-old female rats compared with age-matched male rats. A balance between
      estrogens and vascular contractility might preserve FMR in mature female rats.

PMID- 24929855
TI  - Ambient and household air pollution: complex triggers of disease.
AB  - Concentrations of outdoor air pollution are on the rise, particularly due to
      rapid urbanization worldwide. Alternatively, poor ventilation, cigarette smoke,
      and other toxic chemicals contribute to rising concentrations of indoor air
      pollution. The World Health Organization recently reported that deaths
      attributable to indoor and outdoor air pollutant exposure are more than double
      what was originally documented. Epidemiological, clinical, and animal data have
      demonstrated a clear connection between rising concentrations of air pollution
      (both indoor and outdoor) and a host of adverse health effects. During the past
      five years, animal, clinical, and epidemiological studies have explored the
      adverse health effects associated with exposure to both indoor and outdoor air
      pollutants throughout the various stages of life. This review provides a summary
      of the detrimental effects of air pollution through examination of current
      animal, clinical, and epidemiological studies and exposure during three different
      periods: maternal (in utero), early life, and adulthood. Additionally, we
      recommend future lines of research while suggesting conceivable strategies to
      curb exposure to indoor and outdoor air pollutants.

PMID- 24929857
TI  - High-fat, low-carbohydrate diet promotes arrhythmic death and increases
      myocardial ischemia-reperfusion injury in rats.
AB  - High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety
      of reasons, but the effects of such diets on the heart are incompletely
      understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion
      (I/R) using an in vivo model of left anterior descending coronary artery
      ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30%
      protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65%
      carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline
      (preischemia), diet did not affect left ventricular (LV) systolic and diastolic
      function. Oil red O staining revealed presence of lipid in the heart with HFLCD
      but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD.
      HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3
      gene and protein expression. HFLCD downregulated mitochondrial fusion proteins
      and upregulated fission proteins and store-operated Ca(2+) channel proteins.
      HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD
      rats died due to ventricular arrhythmias and hemodynamic shock. In surviving
      rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not
      affect nonischemic LV function but leads to greater myocardial injury during I/R,
      with increased risk of death by pump failure and ventricular arrhythmias, which
      might be associated with altered cardiac energetics, mitochondrial fission/fusion
      dynamics, and store-operated Ca(2+) channel expression. 

PMID- 24929859
TI  - Docosapentaenoic acid monoacylglyceride reduces inflammation and vascular
      remodeling in experimental pulmonary hypertension.
AB  - n-3 Polyunsaturated fatty acids (n-3 PUFA) have been shown to reduce inflammation
      and proliferation of pulmonary artery smooth muscle cells under
      pathophysiological conditions. However, the anti-inflammatory effect of the newly
      synthesized docosapentaenoic acid monoacylglyceride (MAG-DPA) on key signaling
      pathways in pulmonary hypertension (PH) pathogenesis has yet to be assessed. The
      aim of the present study was to determine the effects of MAG-DPA on pulmonary
      inflammation and remodeling occurring in a rat model of PH, induced by a single
      injection of monocrotaline (MCT: 60 mg/kg). Our results demonstrate that MAG-DPA
      treatment for 3 wk following MCT injection resulted in a significant improvement
      of right ventricular hypertrophy (RVH) and a reduction in Fulton's Index (FI).
      Morphometric analyses revealed that the wall thickness of pulmonary arterioles
      was significantly lower in MCT + MAG-DPA-treated rats compared with controls.
      This result was further correlated with a decrease in Ki-67 immunostaining.
      Following MAG-DPA treatments, lipid analysis showed a consistent increase in DPA
      together with lower levels of arachidonic acid (AA), as measured in blood and
      tissue samples. Furthermore, in MCT-treated rats, oral administration of MAG-DPA
      decreased NF-kappaB and p38 MAPK activation, leading to a reduction in MMP-2, MMP
      9, and VEGF expression levels in lung tissue homogenates. Altogether, these data
      provide new evidence regarding the mode of action of MAG-DPA in the prevention of
      pulmonary hypertension induced by MCT.

PMID- 24929861
TI  - A growth model of saccular aneurysms based on hemodynamic and morphologic
      discriminant parameters for risk of rupture.
AB  - The aim of this study was to derive a model describing the evolution of
      bifurcation type cerebral aneurysms based on morphological and hemodynamic
      parameters. Idealized bifurcation models were constructed based on the two
      morphological parameters of aspect ratio (AR) and size ratio (SR). Aneurysm
      development was investigated according to the following four patterns: R1,
      increasing SR with constant AR; R2, increasing AR with constant SR; R3,
      increasing SR and increasing AR; R4, increasing AR with constant parent artery
      diameter. Relationships were obtained between energy loss (EL) and morphological
      parameters (EL-SR and EL-AR curves). The curves were validated by mapping the
      growth of a ruptured patient-specific bifurcation aneurysm at three stages of
      follow-up. EL increased in parallel with growth patterns R1 and R3, whereas
      growth pattern R2 showed a decrease in EL. No significant changes were observed
      in EL when the growth of the aneurysm was associated only with changes in
      aneurysm size and independent of changes in parent artery diameter and main flow
      (R4). Changes in parent artery diameter of bifurcation aneurysms resulted in
      significant variation in EL. Mapping the growth of a follow-up aneurysm onto the
      EL-AR curve demonstrated that aneurysms with increasing EL during the observation
      period are at higher risk of rupture than aneurysms with decreasing EL. Based on
      the proposed growth model, assessment of morphological (AR and SR) and
      hemodynamic (EL) parameters may provide quantifiable information on the risk of
      bifurcation aneurysm rupture during clinical patient follow-up. 

PMID- 24929858
TI  - Artery buckling stimulates cell proliferation and NF-kappaB signaling.
AB  - Tortuous carotid arteries are often seen in aged populations and are associated
      with atherosclerosis, but the underlying mechanisms to explain this preference
      are unclear. Artery buckling has been suggested as one potential mechanism for
      the development of tortuous arteries. The objective of this study, accordingly,
      was to determine the effect of buckling on cell proliferation and associated NF
      kappaB activation in arteries. We developed a technique to generate buckling in
      porcine carotid arteries using long artery segments in organ culture without
      changing the pressure, flow rate, and axial stretch ratio. Using this technique,
      we examined the effect of buckling on arterial wall remodeling in 4-day organ
      culture under normal and hypertensive pressures. Cell proliferation, NF-kappaB
      p65, IkappaB-alpha, ERK1/2, and caspase-3 were detected using
      immunohistochemistry staining and immunoblot analysis. Our results showed that
      cell proliferation was elevated 5.8-fold in the buckling group under hypertensive
      pressure (n = 7, P < 0.01) with higher levels of NF-kappaB nuclear translocation
      and IkappaB-alpha degradation (P < 0.05 for both). Greater numbers of
      proliferating cells were observed on the inner curve side of the buckled arteries
      compared with the outer curve side (P < 0.01). NF-kappaB colocalized with
      proliferative nuclei. Computational simulations using a fluid-structure
      interaction model showed reduced wall stress on the inner side of buckled
      arteries and elevated wall stress on the outer side. We conclude that arterial
      buckling promotes site-specific wall remodeling with increased cell proliferation
      and NF-kappaB activation. These findings shed light on the biomechanical and
      molecular mechanisms of the pathogenesis of atherosclerosis in tortuous arteries.

PMID- 24929860
TI  - beta(2)-Adrenoreceptor blockade improves early posttrauma hyperglycemia and
      pulmonary injury in obese rats.
AB  - Early hyperglycemia after trauma increases morbidity and mortality. Insulin is
      widely used to control posttrauma glucose, but this treatment increases the risk
      of hypoglycemia. We tested a novel method for early posttrauma hyperglycemia
      control by suppressing hepatic glycogenolysis via beta2-adrenoreceptor blockade
      [ICI-118551 (ICI)]. We have shown that, after severe trauma, obese Zucker (OZ)
      rats, similar to obese patients, exhibit increased acute lung injury compared
      with lean Zucker (LZ) rats. We hypothesized that OZ rats exhibit a greater
      increase in early posttrauma glucose compared with LZ rats, with the increased
      posttrauma hyperglycemia suppressed by ICI treatment. Orthopedic trauma was
      applied to both hindlimbs in LZ and OZ rats. Fasting plasma glucose was then
      monitored for 6 h with or without ICI (0.2 mg.kg(-1).h(-1) iv.) treatment. One
      day after trauma, plasma IL-6 levels, lung neutrophil numbers, myeloperoxidase
      (MPO) activity, and wet-to-dry weight ratios were measured. Trauma induced rapid
      hepatic glycogenolysis, as evidenced by decreased liver glycogen levels, and this
      was inhibited by ICI treatment. Compared with LZ rats, OZ rats exhibited higher
      posttrauma glucose, IL-6, lung neutrophil infiltration, and MPO activity. Lung
      wet-to-dry weight ratios were increased in OZ rats but not in LZ rats. ICI
      treatment reduced the early hyperglycemia, lung neutrophil retention, MPO
      activity, and wet-to-dry weight ratio in OZ rats to levels comparable with those
      seen in LZ rats, with no effect on blood pressure or heart rate. These results
      demonstrate that beta2-adrenoreceptor blockade effectively reduces the early
      posttrauma hyperglycemia, which is associated with decreased lung injury in OZ
      rats. 

PMID- 24929856
TI  - Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular
      system.
AB  - Dipeptidylpeptidase-4 (DPP-4) is a ubiquitously expressed transmembrane protein
      that removes NH2-terminal dipeptides from various substrate hormones, chemokines,
      neuropeptides, and growth factors. Two known substrates of DPP-4 include the
      incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide,
      which are secreted by enteroendocrine cells in response to postprandial
      hyperglycemia and account for 60-70% of postprandial insulin secretion. DPP-4
      inhibitors (DPP-4i) block degradation of GLP-1 and gastric inhibitory peptide,
      extend their insulinotropic effect, and improve glycemia. Since 2006, several DPP
      4i have become available for treatment of type 2 diabetes mellitus. Clinical
      trials confirm that DPP-4i raises GLP-1 levels in plasma and improves glycemia
      with very low risk for hypoglycemia and other side effects. Recent studies also
      suggest that DPP-4i confers cardiovascular and kidney protection, beyond glycemic
      control, which may reduce the risk for further development of the multiple
      comorbidities associated with obesity/type 2 diabetes mellitus, including
      hypertension and cardiovascular disease (CVD) and kidney disease. The notion that
      DPP-4i may improve CVD outcomes by mechanisms beyond glycemic control is due to
      both GLP-1-dependent and GLP-1-independent effects. The CVD protective effects by
      DPP-4i result from multiple factors including insulin resistance, oxidative
      stress, dyslipidemia, adipose tissue dysfunction, dysfunctional immunity, and
      antiapoptotic properties of these agents in the heart and vasculature. This
      review focuses on cellular and molecular mechanisms mediating the CVD protective
      effects of DPP-4i beyond favorable effects on glycemic control.

PMID- 24929862
TI  - Neuropsychiatric disturbance after aneurysmal subarachnoid hemorrhage.
AB  - Although aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 3-5% of all
      strokes, a high degree of morbidity has been reported in this relatively young
      subset of patients. Neuropsychiatric disturbance has often been neglected in
      these reports. We aimed to investigate the pattern and pathological factors of
      chronic neuropsychiatric disturbance in aSAH patients. This cross-sectional
      observational four-center study was carried out in Hong Kong. Neuropsychiatric
      outcome (Neuropsychiatric Inventory Chinese Version [CNPI]) assessments were
      conducted cross-sectionally 1-4 years after ictus. Pathological factors
      considered were early brain injury as assessed by admission World Federation of
      Neurosurgical Societies grade, aneurysm treatment (clipping versus coiling),
      delayed cerebral infarction, and chronic hydrocephalus. One hundred and three
      aSAH patients' spouses or caregivers completed the CNPI. Forty-two (41%) patients
      were reported to have one or more domain(s) of neuropsychiatric disturbance.
      Common neuropsychiatric disturbance domains included agitation/aggression,
      depression, apathy/indifference, irritability/lability, and appetite/eating
      disturbance. Chronic neuropsychiatric disturbance was associated with presence of
      chronic hydrocephalus. A subscore consisting of the five commonly affected
      domains seems to be a suitable tool for aSAH patients and should be further
      validated and replicated in future studies.

PMID- 24929863
TI  - KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas.
AB  - The family of karyopherins comprises importins and exportins which are both
      involved in nucleocytoplasmic shuttling. Increased levels of karyopherin
      a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1
      (CRM1) have been associated with poorer prognosis in patients with infiltrative
      astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was
      also recently identified as a prognostic factor for malignant gliomas. We
      evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel
      biomarkers for World Health Organization grade III anaplastic oligoastrocytomas
      (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72
      primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic
      oligodendrogliomas). The IDH1 mutation status was also determined in patients
      with anaplastic astrocytomas and AOA, and AOA patients were additionally
      evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with
      AOA showed lower KPNA2 expression levels compared to non-LTS (p=0.005). KPNA2
      expression (? 5% versus <5%, 1-<5%, median) was found to correlate inversely with
      overall survival (OS) and progression-free survival (PFS) in our overall series
      as well as in the AOA group (anaplastic gliomas: OS p=0.017; PFS p=0.033; AOA: OS
      p=0.017, PFS p=0.040). Mutant IDH1-R132H was detected in 69% of the AOA cohort; a
      combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS
      (p=0.050). No differences between the histological subtypes were observed in
      terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this
      is the first time it has been shown that KPNA2 expression may have potential as a
      prognostic biomarker for AOA as well.

PMID- 24929866
TI  - IL-18 promoter polymorphisms under scrutiny.

PMID- 24929865
TI  - FOLFOX as second-line chemotherapy in patients with pretreated metastatic
      pancreatic cancer from the FIRGEM study.
AB  - BACKGROUND: FOLFOX second-line treatment seems to be a validated option for
      patients with pancreatic cancer (PC) progressing after gemcitabine chemotherapy.
      However, other therapeutics strategy has developed in first-line therapy, as the
      FIRGEM phase II study that evaluated gemcitabine alone versus FOLFIRI.3
      alternating with gemcitabine every two months. The present study assessed the
      efficacy and safety of FOLFOX after failure of the first-line therapy used in the
      FIRGEM study. METHODS: In this prospective observational cohort study, we
      analysed all consecutive patients who received second-line chemotherapy with
      FOLFOX among 98 patients with metastatic PC included in the FIRGEM study.
      Progression-free survival (PFS) and overall survival (OS) were estimated from the
      start of second-line chemotherapy using the Kaplan-Meier method. RESULTS: Among
      46 patients who received second-line chemotherapy, 27 patients (male, 55%; median
      age, 61 years; performance status (PS) 0-1, 44%) were treated with FOLFOX after
      progression to first-line gemcitabine alone (n = 20) or FOLFIRI.3 alternating
      with gemcitabine (n = 7). Grade 3 toxicity was observed in 33% of patients (no
      grade 4 toxicity). At the end of follow-up, all patients had progressed and 25
      had died. No objective response was observed, and disease control rate was 36%.
      Median PFS and OS were 1.7 and 4.3 months, respectively. In multivariate
      analysis, PS was the only independent prognostic factor. For patients PS 0-1
      versus 2-3, median PFS was 3.0 versus 1.2 months (log rank, p = 0.002), and
      median OS was 5.9 versus 2.6 months (log rank, p = 0.001). CONCLUSIONS: This
      study suggests that FOLFOX second-line therapy offered interesting efficacy
      results with an acceptable toxicity profile in metastatic PC patients with a good
      PS.

PMID- 24929864
TI  - Prefrontal cortical regulation of fear learning.
AB  - The prefrontal cortex regulates the expression of fear based on previously
      learned information. Recently, this brain area has emerged as being crucial in
      the initial formation of fear memories, providing new avenues to study the
      neurobiology underlying aberrant learning in anxiety disorders. Here we review
      the circumstances under which the prefrontal cortex is recruited in the formation
      of memory, highlighting relevant work in laboratory animals and human subjects.
      We propose that the prefrontal cortex facilitates fear memory through the
      integration of sensory and emotional signals and through the coordination of
      memory storage in an amygdala-based network. 

PMID- 24929867
TI  - Improving the resolution in proton-detected through-space heteronuclear multiple
      quantum correlation NMR spectroscopy.
AB  - Connectivities and proximities between protons and low-gamma nuclei can be probed
      in solid-state NMR spectroscopy using two-dimensional (2D) proton-detected
      heteronuclear correlation, through Heteronuclear Multiple Quantum Correlation
      (HMQC) pulse sequence. The indirect detection via protons dramatically enhances
      the sensitivity. However, the spectra are often broadened along the indirect F1
      dimension by the decay of heteronuclear multiple-quantum coherences under the
      strong (1)H-(1)H dipolar couplings. This work presents a systematic comparison of
      the performances of various decoupling schemes during the indirect t1 evolution
      period of dipolar-mediated HMQC (D-HMQC) experiment. We demonstrate that (1)H
      (1)H dipolar decoupling sequences during t1, such as symmetry-based schemes,
      phase-modulated Lee-Goldburg (PMLG) and Decoupling Using Mind-Boggling
      Optimization (DUMBO), provide better resolution than continuous wave (1)H
      irradiation. We also report that high resolution requires the preservation of
      (1)H isotropic chemical shifts during the decoupling sequences. When observing
      indirectly broad spectra presenting numerous spinning sidebands, the D-HMQC
      sequence must be fully rotor-synchronized owing to the rotor-synchronized
      indirect sampling and dipolar recoupling sequence employed. In this case, we
      propose a solution to reduce artefact sidebands caused by the modulation of
      window delays before and after the decoupling application during the t1 period.
      Moreover, we show that (1)H-(1)H dipolar decoupling sequence using Smooth
      Amplitude Modulation (SAM) minimizes the t1-noise. The performances of the
      various decoupling schemes are assessed via numerical simulations and compared to
      2D (1)H-{(13)C} D-HMQC experiments on [U-(13)C]-L-histidine?HCl?H2O at various
      magnetic fields and Magic Angle spinning (MAS) frequencies. Great resolution and
      sensitivity enhancements resulting from decoupling during t1 period enable the
      detection of heteronuclear correlation between aliphatic protons and ammonium
      (14)N sites in L-histidine?HCl?H2O. 

PMID- 24929868
TI  - Behavior of TiO2 nanoparticles during incineration of solid paint waste: a lab
      scale test.
AB  - In order to assess the potential impacts posed by products containing engineered
      nanoparticles, it is essential to generate more data about the release of these
      particles from products' life cycle. Although first studies were performed to
      investigate the release of nanoparticles from use phase, very few data are
      available on the potential release from recycling or disposal of nano-enhanced
      products. In this work, we investigated the behavior of TiO2 nanoparticles from
      incineration of solid paint waste containing these particles. Solid paint debris
      with and without TiO2 nanoparticles were treated in a lab scale incineration
      plant at 950 degrees C (combustion temperature) and in oxidizing atmosphere. The
      obtained ashes were also vitrified with additives and the release of Ti was
      finally evaluated by leaching test. From our incineration lab-scale experiment,
      we did not observe a release of TiO2 nanoparticles into the atmosphere, and Ti
      was attached to the surface of obtained solid residues (i.e. ashes). The
      characterization of ashes showed that TiO2 nanoparticles reacted during the
      incineration to give calcium titanate. Finally, a very low release of Ti was
      measured, less 1 mg/kg, during the leaching test of ashes vitrified with glass
      cullet and feldspathic inert. Our work suggests that TiO2 nanoparticles added in
      paints may undergo to physicochemical transformation during the incineration, and
      that Ti found in ashes may be strongly immobilized in glass matrix. Since this
      conclusion is based on lab-scale experiment, further research is required to
      identify which nanoparticles will be emitted to the environment from a real-word
      incineration system of household hazardous waste.

PMID- 24929869
TI  - Predicting final product properties of melt extruded solid dispersions from
      process parameters using Raman spectrometry.
AB  - Raman spectrometry was utilized to estimate degraded drug percentage, residual
      drug crystallinity and glass-transition temperature in the case of melt-extruded
      pharmaceutical products. Tight correlation was shown between the results obtained
      by confocal Raman mapping and transmission Raman spectrometry, a PAT-compatible
      potential in-line analytical tool. Immediate-release spironolactone-Eudragit E
      solid dispersions were the model system, owing to the achievable amorphization
      and the heat-sensitivity of the drug compound. The deep investigation of the
      relationship between process parameters, residual drug crystallinity and
      degradation was performed using statistical tools and a factorial experimental
      design defining 54 different circumstances for the preparation of solid
      dispersions. From the examined factors, drug content (10, 20 and 30%),
      temperature (110, 130 and 150 degrees C) and residence time (2.75, 11.00 and
      24.75min) were found to have significant and considerable effect. By forming
      physically stable homogeneous dispersions, the originally very slow dissolution
      of the lipophilic and poorly water-soluble spironolactone was reasonably
      improved, making 3minute release possible in acidic medium. 

PMID- 24929870
TI  - Quantitative risk assessment in classification of drugs with identical API
      content.
AB  - When combating counterfeits it is equally important to recognize fakes and to
      avoid misclassification of genuine samples. This study presents a general
      approach to the problem using a newly-developed method called Data Driven Soft
      Independent Modeling of Class Analogy. The possibility to collect representative
      data for both training and validation is of great importance in classification
      modeling. When fakes are not available, we propose to compose the test set using
      the legitimate drug's analogs, manufactured by various producers. These analogs
      should have the identical API and a similar composition of excipients. The
      approach shows satisfactory results both in revealing counterfeits and in
      accounting for the future variability of the target class drugs. The presented
      case studies demonstrate that theoretically predicted misclassification errors
      can be successfully employed for the science-based risk assessment in drug
      identification. 

PMID- 24929872
TI  - The Acute Cardiovascular Care Association Clinical Decision-Making Toolkit.

PMID- 24929871
TI  - A surrogate analyte-based LC-MS/MS method for the determination of gamma
      hydroxybutyrate (GHB) in human urine and variation of endogenous urinary
      concentrations of GHB.
AB  - gamma-Hydroxybutyrate (GHB) is a drug of abuse with a strong anesthetic effect;
      however, proving its ingestion through the quantification of GHB in biological
      specimens is not straightforward due to the endogenous presence of GHB in human
      blood, urine, saliva, etc. In the present study, a surrogate analyte approach was
      applied to accurate quantitative determination of GHB in human urine using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) in order to overcome this
      issue. For this, (2)H6-GHB and (13)C2-dl-3-hydroxybutyrate were used as a
      surrogate standard and as an internal standard, respectively, and parallelism
      between the surrogate analyte approach and standard addition was investigated at
      the initial step. The validation results proved the method to be selective,
      accurate, and precise, with acceptable linearity within calibration ranges (0.1
      1MUg/ml). The limit of detection and the limit of quantification of (2)H6-GHB
      were 0.05 and 0.1MUg/ml, respectively. No significant variations were observed
      among urine matrices from different sources. The stability of (2)H6-GHB was
      satisfactory under sample storage and in-process conditions. However, in vitro
      production of endogenous GHB was observed when the urine sample was kept under
      the in-process condition for 4h and under the storage conditions of 4 and -20
      degrees C. In order to facilitate the practical interpretation of urinary GHB,
      endogenous GHB was accurately measured in urine samples from 79 healthy
      volunteers using the surrogate analyte-based LC-MS/MS method developed in the
      present study. The unadjusted and creatinine-adjusted GHB concentrations in 74
      urine samples with quantitative results ranged from 0.09 to 1.8MUg/ml and from
      4.5 to 530MUg/mmol creatinine, respectively. No significant correlation was
      observed between the unadjusted and creatinine-adjusted GHB concentrations. The
      urinary endogenous GHB concentrations were affected by gender and age while they
      were not significantly influenced by habitual smoking, alcohol drinking, or
      caffeine-containing beverage drinking. 

PMID- 24929873
TI  - Recurrent mid-ventricular takotsubo cardiomyopathy.

PMID- 24929874
TI  - Association between dietary fiber intake and risk of coronary heart disease: A
      meta-analysis.
AB  - BACKGROUND & AIMS: The association between coronary heart disease (CHD) and
      dietary fiber intake is not consistent, especially for the subtypes of dietary
      fiber. The aim of our study was to conduct a meta-analysis of existing cohort
      published studies assessing the association between dietary fiber intake and risk
      of CHD, and quantitatively estimating their dose-response relationships. METHODS:
      We searched PubMed and EMBASE before May 2013. Random-effect model was used to
      calculate the pool relative risk (RRs) for the incidence and mortality of CHD.
      Dose-response, subgroup analyses based on fiber subtypes, heterogeneity and
      publication bias were also carried out. RESULTS: Eighteen studies involving
      672,408 individuals were finally included in the present study. The pooled
      adjusted RRs of coronary heart disease for the highest versus lowest category of
      fiber intake were 0.93 (95% confidence interval (CI), 0.91-0.96, P < 0.001) for
      incidence of all coronary events and 0.83 (95% CI, 0.76-0.91, P < 0.001) for
      mortality. Further subgroup analyses based on fiber subtypes (cereal, fruit, and
      vegetable fiber), indicated that RRs were 0.92 (95% CI, 0.85-0.99, P = 0.032),
      0.92 (95% CI, 0.86-0.98, P = 0.01), 0.95 (95% CI, 0.89-1.01, P = 0.098)
      respectively for all coronary event and 0.81 (95% CI, 0.72-0.92, P = 0.001), 0.68
      (95% CI, 0.43-1.07, P = 0.094), 0.91 (95% CI, 0.74-1.12, P = 0.383) for
      mortality. In addition, a significant dose-response relationship was observed
      between fiber intake and the incidence and mortality of CHD (P < 0.001).
      CONCLUSIONS: Our results indicate that consumption of dietary fiber is inversely
      associated with risk of coronary heart disease, especially for fiber from cereals
      and fruits. Besides, soluble and insoluble fibers have the similar effect. A
      significant dose-response relationship is also observed between fiber intake and
      CHD risk.

PMID- 24929875
TI  - Increasing prevalence of hydrogen sulfide negative Salmonella in retail meats.
AB  - Hydrogen sulfide (H2S) production is considered a typical characteristic of
      Salmonella and an important marker for Salmonella isolation. In this study, a
      total of 82 (26%) Salmonella strains were isolated from 113 chicken and 204 pork
      samples, within which 49 Salmonella strains were H2S positive and 33 were H2S
      negative. Salmonella enterica serovar Derby was most prevalent in both pork and
      chicken followed by S. Typhimurium in pork and S. Heidelberg in chicken.
      Salmonella isolated from pork exhibited a much higher H2S positive rate than
      those from chicken (68% versus 31%). The most prevalent H2S negative serotypes
      were S. Derby (40%) and S. Heidelberg (30%) in chicken, and S. Typhimurium (23%)
      and S. Enteritidis (23%) in pork. spvC, a plasmid-encoded virulence marker, was
      detected in 51% and 42% of the H2S positive and negative Salmonella respectively.
      The presence of the two most important serotypes, S. Enteritidis and S.
      Typhimurium, as well as a virulence plasmid in H2S negative Salmonella suggested
      that H2S negative Salmonella is also a significant public health concern. Such
      finding warrants the development of an improved method for effective coverage of
      H2S negative Salmonella. 

PMID- 24929876
TI  - Use of non-Saccharomyces wine yeasts as novel sources of mannoproteins in wine.
AB  - Eight non-Saccharomyces wine strains, previously selected for their ability to
      modulate the final concentrations of various volatile compounds and to persist
      with Saccharomyces cerevisiae in mixed inocula fermentations of grape juice, have
      been analyzed in the present work to test their ability to release mannoproteins.
      The eight strains were members of different genera originally isolated from
      grape: Hansensiaspora osmophila, Lachancea thermotolerans, Metschnikowia
      pulcherrima, Pichia fermentans, Saccharomycodes ludwigii, Starmerella bacillaris,
      Torulaspora delbrueckii and Zygosaccharomyces florentinus. A synthetic
      polysaccharide-free grape juice, was used to characterize the mannoproteins
      released during the alcoholic fermentation. Mannoproteins profiles were
      characterized by gel electrophoresis and carbohydrate composition was analyzed
      both by HPLC and by mass spectrometry. The eight non-Saccharomyces yeasts
      demonstrated a higher capacity to release polysaccharides compared to S.
      cerevisiae. The proteins released by the eight yeast strains showed a wide
      variety of protein sizes, ranging from 25 kDa to greater than 250 kDa. The mass
      spectrometric profile of the N-glycans ranged from 1600 to 4000 Da and was
      characteristic for each strain. Detailed investigation of the degree of
      polymerization of released N-glycans revealed variable composition from 8 to 15
      units of monosaccharides. 

PMID- 24929877
TI  - Assessment of the risk of salmonellosis from internally contaminated shell eggs
      following initial storage at 18  degrees C (65  degrees F), compared with 7 
      degrees C (45  degrees F).
AB  - In the U.S., chicken-breeder farms that supply hatcheries typically store and
      transport eggs intended for broiler production at a temperature of 18.3  degrees
      C (65  degrees F). However, in case of surplus, some of these eggs may be
      diverted to human consumption. According to the U.S. Food and Drug
      Administration's 'Egg Safety Final Rule,' shell eggs intended for human
      consumption are required to be held or transported at or below 7.2  degrees C (45
      degrees F) ambient temperature beginning 36 h after time of lay. We adapted a
      risk assessment model developed by the U.S. Department of Agriculture's Food
      Safety Inspection Service, to quantify human exposure to Salmonella Enteritidis
      and the risk of human salmonellosis if eggs are held and transported at 18.3 
      degrees C for up to 5.5 days after time of lay, as has been observed when
      hatchery eggs are diverted to human consumption, rather than held and transported
      at 7.2  degrees C within 36 h after time of lay. Storage at 18.3  degrees C leads
      to considerable bacterial growth in internally contaminated eggs. The model
      predicted that more than 10% of internally contaminated eggs would remain
      contaminated after in-shell pasteurization resulting in a 5-log10 reduction, and
      that some bacteria would survive after home-cooking. The model predicted that,
      alternatively, eggs stored at 7.2  degrees C after lay would have limited
      bacterial growth prior to pasteurization, and Salmonella would be very unlikely
      to be present after pasteurization. The predicted risk of salmonellosis from the
      consumption of eggs held and transported at 18.3  degrees C and subsequently
      diverted to human consumption is 25 times higher than the risk when eggs are held
      and transported at 7.2  degrees C. 

PMID- 24929879
TI  - Rapid detection and differentiation of important Campylobacter spp. in poultry
      samples by dot blot and PCR.
AB  - The detection of Campylobacter, the most commonly reported cause of foodborne
      gastroenteritis in the European Union, is very important for human health. The
      most commonly recognised risk factor for infection is the handling and/or
      consumption of undercooked poultry meat. The methods typically applied to
      evaluate the presence/absence of Campylobacter in food samples are direct plating
      and/or enrichment culture based on the Horizontal Method for Detection and
      Enumeration of Campylobacter spp. (ISO 10272-1B: 2006) and PCR. Molecular methods
      also allow for the detection of cells that are viable but cannot be cultivated on
      agar media and that decrease the time required for species identification. The
      current study proposes the use of two molecular methods for species
      identification: dot blot and PCR. The dot blot method had a sensitivity of 25 ng
      for detection of DNA extracted from a pure culture using a digoxigenin-labelled
      probe for hybridisation; the target DNA was extracted from the enrichment broth
      at 24 h. PCR was performed using a pair of sensitive and specific primers for the
      detection of Campylobacter jejuni and Campylobacter coli after 24 h of enrichment
      in Preston broth. The initial samples were contaminated by 5 * 10 C. jejuni
      cells/g and 1.5 * 10(2)C. coli cells/g, thus the number of cells present in the
      enrichment broth at 0 h was 1 or 3 cell/g, respectively. 

PMID- 24929878
TI  - Effects of nitrogen and potassium fertilization on the susceptibility of tomatoes
      to post-harvest proliferation of Salmonella enterica.
AB  - Fresh fruits and vegetables are increasingly recognized as vehicles of
      salmonellosis. Pre- and post-harvest environmental conditions, and physiological,
      and genetic factors are thought to contribute to the ability of human pathogens
      to persist in the production environment, attach to, colonize and proliferate in
      and on raw produce. How field production conditions affect the post-harvest food
      safety outcomes is not entirely understood. This study tested how varying
      nitrogen and potassium fertilization levels affected the "susceptibility" of
      tomatoes to Salmonella infections following the harvest of fruits. Two tomato
      varieties grown over three seasons under high, medium, and low levels of nitrogen
      and potassium fertilization in two locations were inoculated with seven strains
      of Salmonella. Even though the main effects of nitrogen and potassium
      fertilization on the susceptibility of tomatoes to infections with Salmonella
      enterica were not statistically significant overall, differences in nitrogen
      concentrations in plant tissues correlated with the susceptibility of partially
      ripe tomatoes (cv. Solar Fire) to Salmonella. Tomato maturity and the season in
      which tomatoes were produced had the strongest effect on the ability of
      Salmonella to multiply in tomatoes. Tomato phenolics, accumulation of which is
      known to correlate with rates of the N fertilization, did not inhibit growth of
      Salmonella in vitro. 

PMID- 24929880
TI  - Development of 23 individual TaqMan(r) real-time PCR assays for identifying
      common foodborne pathogens using a single set of amplification conditions.
AB  - Most of the acute intestinal diseases are caused by foodborne pathogens with
      infants and elderly people being at major risk. The aim of this study was to
      develop a procedure to simultaneously detect 20 foodborne pathogens in complex
      alimentary matrices such as milk, cheese and meat. The list of targets include,
      among the others, Listeria spp., Salmonella spp., Shigella spp., Escherichia coli
      spp., Campylobacter spp., Clostridium spp. and Staphylococcus aureus. The
      accuracy of detection was determined by using ATCC strains as positive and
      negative controls. The achieved sensitivity of each of assays was 1 pg of genomic
      DNA, which was equivalent to ~1 cfu. The working ranges of the TaqMan((r)) Real
      time PCR assays, when used quantitatively on cheese and meat samples inoculated
      with serial dilution of Listeria spp., Listeria monocytogenes, S. aureus,
      Salmonella enterica, Shigella boydii, E. coli O157:H7, Bacillus cereus,
      Campylobacter coli, Yersinia enterocolitica, Enterobacter sakazakii and
      Pseudomonas aeruginosa was 10(8) cfu/g to 10(4) cfu/g. No matrix interferences
      were observed.

PMID- 24929881
TI  - Development of a Multiplex-PCR assay for the rapid identification of Geobacillus
      stearothermophilus and Anoxybacillus flavithermus.
AB  - The presence of thermophilic bacilli in dairy products is indicator of poor
      hygiene. Their rapid detection and identification is fundamental to improve the
      industrial reactivity in the implementation of corrective and preventive actions.
      In this study a rapid and reliable identification of Geobacillus
      stearothermophilus and Anoxybacillus flavithermus was achieved by species
      specific PCR assays. Two primer sets, targeting the ITS 16S-23S rRNA region and
      the rpoB gene sequence of the target species respectively, were employed. Species
      specificity of both primer sets was evaluated by using 53 reference strains of
      DSMZ collection; among them, 13 species of the genus Geobacillus and 15 of the
      genus Anoxybacillus were represented. Moreover, 99 wild strains and 23 bulk cells
      collected from 24 infant formula powders gathered from several countries
      worldwide were included in the analyses. Both primer sets were highly specific
      and the expected PCR fragments were obtained only when DNA from G.
      stearothermophilus or A. flavithermus was used. After testing their specificity,
      they were combined in a Multiplex-PCR assay for the simultaneous identification
      of the two target species. The specificity of the Multiplex-PCR was evaluated by
      using both wild strains and bulk cells. Every analysis confirmed the reliable
      identification results provided by the single species-specific PCR methodology.
      The easiness, the rapidity (about 4 h from DNA isolation to results) and the
      reliability of the PCR procedures developed in this study highlight the advantage
      of their application for the specific detection and identification of the
      thermophilic species G. stearothermophilus and A. flavithermus. 

PMID- 24929882
TI  - High prevalence of pathogenic Yersinia enterocolitica in pig cheeks.
AB  - Samples from pork cuts for minced meat and cheeks from processing plants and a
      slaughterhouse, and modified atmosphere (MA) packaged pork from retail were
      studied to estimate the prevalence of pathogenic, i.e. virulence plasmid bearing,
      Yersinia enterocolitica and Yersinia pseudotuberculosis in pork, as well as to
      quantify pathogenic Y. enterocolitica in pork cuts. Pathogenic (virF-positive) Y.
      enterocolitica was isolated from 17 pig cheeks (23%) but not from any of the MA
      packaged 54 retail pork samples and only from one of the 155 pork cut (0.6%).
      Most (16/17) of the cheek samples were contaminated with pathogenic Y.
      enterocolitica 4/O:3 and one with bioserotype 2/O:9. No Y. pseudotuberculosis was
      isolated. The prevalence of pathogenic Y. enterocolitica was clearly higher (39%)
      in 155 pork cuts when studied with nested PCR targeting yadA on the virulence
      plasmid pYV although the contamination level was low varying between 0.1 and 1.6
      MPN/g. Raw pork cuts and especially pig cheeks may serve as possible sources for
      yersiniosis caused by pathogenic Y. enterocolitica. 

PMID- 24929883
TI  - An investigator-initiated, double-blind, vehicle-controlled pilot study:
      assessment for tachyphylaxis to topically occluded halobetasol 0.05% ointment in
      the treatment of psoriasis.
AB  - BACKGROUND: Topical corticosteroids are the most common first-line treatment for
      psoriasis. Tachyphylaxis, a decreased response to treatment with repetitive
      application of the drug, is a controversial phenomenon associated with topical
      corticosteroid treatment. OBJECTIVE: We sought to prove or disprove tachyphylaxis
      to occluded halobetasol 0.05% versus vehicle. METHODS: Patients with plaque
      psoriasis were recruited to this study. The study involved 3 phases (1, 2A, and
      2B) with each phase being separated by a treatment vacation period. In phases 1
      and 2A, 2 plaques were randomized to either halobetasol 0.05% or vehicle ointment
      application. In phase 2B, halobetasol 0.05% was applied to both. Target Lesion
      Severity Scale was used for clinical assessment. RESULTS: Twenty patients were
      enrolled. No difference in time to clearance (P=.88) or time to recurrence
      (P=.92) of the treated plaques was found between phases 1 and 2A. Percentage of
      improvement was higher in phase 2A compared with phase 1 (89.4%, P<.05 vs 71%,
      P<.05), as a result of reduction of vehicle effect. In phase 2B, a greater
      improvement was found for previously corticosteroid-treated plaques. LIMITATIONS:
      Limitations are small sample size and 1 corticosteroid tested. CONCLUSION: No
      evidence of tachyphylaxis to the topical corticosteroid halobetasol 0.05%
      ointment treatment in patients with plaque psoriasis was found.

PMID- 24929884
TI  - An investigator-initiated open-label clinical trial of vismodegib as a
      neoadjuvant to surgery for high-risk basal cell carcinoma.
AB  - BACKGROUND: Vismodegib is an oral hedgehog-pathway inhibitor approved for
      advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery,
      excision of large tumors in aesthetically sensitive sites may compromise function
      or cosmesis. OBJECTIVE: We sought to evaluate the reduction in BCC surgical
      defect area after 3 to 6 months of neoadjuvant vismodegib. METHODS: This was an
      open-label, single-arm intervention trial with a primary outcome of change in
      target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary
      outcomes were change in tumor area and tolerability. RESULTS: Eleven of 15
      enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target
      tumors were excised after a mean of 4+/-2 months of vismodegib. In all, 29% (4 of
      14 patients) could not complete more than 3 months because of vismodegib-related
      side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13
      tumors occurred on the face. Overall, vismodegib reduced the surgical defect area
      by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline.
      Vismodegib was not effective in patients who received less than 3 months. Over a
      mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred
      at 17 months post-Mohs micrographic surgery. LIMITATIONS: Short follow-up time
      and no placebo control are limitations. CONCLUSION: Neoadjuvant vismodegib
      appears to reduce surgical defect area when taken for 3 months or longer for
      nonrecurrent BCCs in functionally sensitive locations. Further studies with
      larger sample sizes and long-term follow-up are warranted.

PMID- 24929885
TI  - The "biker-glove" pattern of segmental infantile hemangiomas on the hands and
      feet.
AB  - BACKGROUND: Infantile hemangiomas (IH) on the extremities have not been
      systematically studied. OBJECTIVE: We sought to describe the clinical
      characteristics and distribution patterns of IH affecting acral surfaces and to
      explore the relationship among these patterns, limb development, and IH
      pathogenesis. METHODS: This was a retrospective multicenter cohort study.
      Photographic archives from 4 tertiary pediatric dermatology referral centers were
      searched for patients with IH larger than 1 cm and involving 1 or more digit.
      Hemangioma location, distribution, and morphologic subtype were recorded. Medical
      records were reviewed for demographic and clinical data. RESULTS: In all, 73
      patients were identified. The most common IH pattern resembled that of a "biker
      glove" (73%), followed by localized IH on the distal digits (14%), segmental IH
      extending over the distal digits (8%), and intermediate patterns (5%). Overall,
      63% of acral IH were segmental, 26% indeterminate, and 11% localized. Five
      patients had associated structural anomalies. Complications were noted in 33% of
      cases. LIMITATIONS: Limitations were retrospective study design; selection bias
      based on recall and photography; documentation and follow-up were not
      standardized across institutions; and treatment information may not reflect
      current approaches. CONCLUSION: Acral IH display specific patterns and are
      associated with a relatively high risk of ulceration.

PMID- 24929886
TI  - Dermatoscopic features of central centrifugal cicatricial alopecia.
AB  - BACKGROUND: No data exist on the dermatoscopic findings in central centrifugal
      cicatricial alopecia (CCCA). OBJECTIVE: We sought to establish the spectrum of
      dermatoscopic features and their frequency in CCCA. METHODS: We retrospectively
      evaluated 153 nonpolarized dermatoscopic images obtained from 51 women with
      histologically proven CCCA and established a list of 12 dermatoscopic features
      that were independently scored for each image. Controls included 30 dermatoscopic
      images from histologically proven cases of scarring traction alopecia and discoid
      lupus erythematosus. The receiver operating characteristic curve analysis
      assessed the specificity and sensitivity; Cohen kappa statistics assessed the
      agreement. Dermatoscopic pathologic correlations were performed on the horizontal
      sections of 41 of the 51 specimens, which were obtained with dermatoscopy-guided
      biopsy procedures. RESULTS: Peripilar white gray halo around the emergence of
      hairs was observed in 94% of patients and was highly specific and sensitive for
      CCCA in all clinical stages. It corresponds on pathology to the lamellar fibrosis
      surrounding the outer root sheath. LIMITATIONS: This was a retrospective study.
      CONCLUSION: The presence of a peripilar white halo is a dermatoscopic feature
      that suggests the diagnosis of CCCA in African American patients with mild
      central thinning, and it is an optimal site from which to obtain a biopsy
      specimen.

PMID- 24929887
TI  - MITA/STING: a central and multifaceted mediator in innate immune response.
AB  - The recognition of nucleic acids is a general strategy used by the host to detect
      invading pathogens. Many studies have established that MITA/STING is a central
      component in the innate immune response to cytosolic DNA and RNA derived from
      pathogens. MITA can act both as a direct sensor of cyclic dinucleotides (CDNs)
      and as an adaptor for the recruitment of downstream signaling components. In both
      roles, MITA is part of signaling cascades that orchestrate innate immune defenses
      against various pathogens, including viruses, bacteria and parasites. Here, we
      highlight recent studies that have uncovered the molecular mechanisms of MITA
      mediated signal transduction and regulation, and discuss some notable issues that
      remain elusive. 

PMID- 24929888
TI  - A randomized trial of misoprostol versus laminaria before dilation and evacuation
      in South Africa.
AB  - OBJECTIVE: To compare complication rates, efficacy and acceptability of buccal
      misoprostol to laminaria for cervical preparation before dilation and evacuation
      (D&E) in South Africa. STUDY DESIGN: We performed a randomized, single-blind
      trial comparing buccal misoprostol 400 mcg (1-2 doses, administered at least 3 h
      before D&E) to laminaria inserted the day before D&E among women at 13-19 weeks
      gestation. The primary outcome was expulsion of the fetus prior to surgery;
      secondary outcomes included other complications, need for mechanical dilation,
      procedure duration, side effects and satisfaction. Required sample size was 176
      to detect a difference in expulsion of 20% to 5%, with a two-sided alpha of 0.05
      and 80% power. RESULTS: Due to slow enrollment and low incidence of primary
      outcome, the study was stopped early. One hundred fifty-nine women were
      randomized, and 156 received treatment (78 in each group). Mean gestational age
      was 14.8 weeks (range, 13.0-18.6 weeks). Complications were rare and did not
      differ by group [three in each group; odds ratio (OR), 1; 95% confidence interval
      (CI), 0.20-5.11]; this included two expulsions in the misoprostol group (2.6%).
      Misoprostol participants were more likely to require mechanical dilation compared
      to those receiving laminaria (35% vs. 8%; OR, 6.4; 95% CI, 2.4-16.5). The
      proportion of women reporting each side effect was similar except for diarrhea
      (21.3% in misoprostol group vs. 5.2% in laminaria group, p=0.004). Procedure time
      and satisfaction did not differ between groups. CONCLUSIONS: Both misoprostol and
      laminaria are associated with a low complication rate in this setting, although
      misoprostol requires more mechanical dilation and causes more diarrhea.
      IMPLICATIONS: Cervical preparation using either laminaria or misoprostol can be
      safely used before D&E up to at least 19 weeks. Physicians using misoprostol must
      be skilled at mechanical dilation, since this is commonly required.

PMID- 24929889
TI  - Pharmacy-based interventions for initiating effective contraception following the
      use of emergency contraception: a pilot study.
AB  - OBJECTIVES: In Scotland most women get emergency contraception (EC) from
      pharmacies. Pharmacists currently cannot provide effective ongoing contraception
      after EC. In this pilot study, we aimed to determine the feasibility of a larger
      study designed to ascertain if pharmacy-based interventions can increase the
      uptake of effective contraception after EC. STUDY DESIGN: This is a pilot study
      of women presenting for levonorgestrel EC to community pharmacies in Edinburgh,
      UK, in 2012. Pharmacies were cluster randomized to provide either standard care
      or one of two interventions: (a) one packet of progestogen-only pills (POPs),
      giving women 1 month to arrange ongoing contraception; (b) invitation to present
      the empty EC packet to a family planning clinic (FPC) for contraceptive advice
      (rapid access). RESULTS: One hundred sixty-eight women were recruited from 11
      pharmacies to POP (n=56), rapid access (n=58) and standard care (N=54) groups,
      respectively. Telephone follow-up was conducted successfully in 102 women (61%) 6
      8 weeks later to determine current contraceptive use. In the POP arm, 35/39 (90%)
      women used the pills provided, and 9/28 women (32%) in the rapid access arm
      attended the FPC. The proportion of women using effective contraception at follow
      up was significantly greater in both POP [56% (22/39), p=<0.001] and rapid access
      [52% (13/25), p=0.006] groups compared to standard care [16% (5/31)]. The
      relative probability of a woman using an effective method of contraception versus
      barrier/no method, after use of EC, was 3.13 [95% confidence interval (CI), 1.90
      5.13] in the POP group and 2.57 (95% CI, 1.55-4.27) in the rapid access group.
      CONCLUSIONS: This promising pilot study suggests that simple pharmacy-based
      interventions may increase the uptake of effective contraception after EC. A
      larger study is required to provide further validation of these findings.
      IMPLICATIONS STATEMENT: For women obtaining EC from a pharmacy, simple
      interventions such as supplying 1 month of a POP, or offering rapid access to a
      FPC, hold promise as strategies to increase the uptake of effective contraception
      after EC.

PMID- 24929890
TI  - Phenotypic drug screening and target validation for improved personalized therapy
      reveal the complexity of phenotype-genotype correlations in clear cell renal cell
      carcinoma.
AB  - OBJECTIVES: Novel personalized therapeutic approaches are urgently needed for
      patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS AND
      MATERIALS: We combined the development of a primary patient-derived ccRCC cell
      line with a phenotypic drug screen consisting of 101 approved anticancer
      compounds. RESULTS: We identified the MNNG HOS transforming gene (MET)-anaplastic
      lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of
      our drug screen, whereas compounds targeting the vascular endothelial growth
      factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only
      minor in vitro activity. Among the known major crizotinib targets MET, ALK, and
      ROS-1, only MET was expressed in our ccRCC cell line. Subsequent sequence
      analysis revealed a heterozygous R988C mutation of the MET gene and a VHL
      deletion in both the primary tumor and the tumor-derived ccRCC cell line.
      However, we were unable to show an activation of MET and, further, MET knockdown
      did not result in increased apoptosis or cytotoxicity. Therefore, our results
      suggest that MET R988C does not function as a major oncogenic driver mutation but
      rather represents a sequence variant. However, we provide evidence that the
      cytotoxic effect of crizotinib in our cell line model correlates with its ability
      to inhibit P-glycoprotein (ABCB1)-associated transport functions. CONCLUSIONS:
      Our study shows that a phenotypic screen of a patient-derived tumor cell line can
      identify compounds with antitumor activity but with an unexpected mode of action.
      Our results underscore that target validation and phenotype-genotype correlations
      remain a major experimental challenge. The implications of our findings for a
      personalized management of patients with cancer are discussed.

PMID- 24929892
TI  - Clustering of metabolic and cardiovascular risk factors in the polycystic ovary
      syndrome: a principal component analysis.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent condition with
      heterogeneity of clinical features and cardiovascular risk factors that implies
      multiple aetiological factors and possible outcomes. OBJECTIVE: To reduce a set
      of correlated variables to a smaller number of uncorrelated and interpretable
      factors that may delineate subgroups within PCOS or suggest pathogenetic
      mechanisms. MATERIALS AND METHODS: We used principal component analysis (PCA) to
      examine the endocrine and cardiometabolic variables associated with PCOS defined
      by the National Institutes of Health (NIH) criteria. Data were retrieved from the
      database of a single clinical endocrinologist. We included women with PCOS (N =
      378) who were not taking the oral contraceptive pill or other sex hormones, lipid
      lowering medication, metformin or other medication that could influence the
      variables of interest. PCA was performed retaining those factors with eigenvalues
      of at least 1.0. Varimax rotation was used to produce interpretable factors.
      RESULTS: We identified three principal components. In component 1, the dominant
      variables were homeostatic model assessment (HOMA) index, body mass index (BMI),
      high density lipoprotein (HDL) cholesterol and sex hormone binding globulin
      (SHBG); in component 2, systolic blood pressure, low density lipoprotein (LDL)
      cholesterol and triglycerides; in component 3, total testosterone and LH/FSH
      ratio. These components explained 37%, 13% and 11% of the variance in the PCOS
      cohort respectively. CONCLUSIONS: Multiple correlated variables from patients
      with PCOS can be reduced to three uncorrelated components characterised by
      insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia. Clustering
      of risk factors is consistent with different pathogenetic pathways within PCOS
      and/or differing cardiometabolic outcomes.

PMID- 24929891
TI  - Elevated alkaline phosphatase velocity strongly predicts overall survival and the
      risk of bone metastases in castrate-resistant prostate cancer.
AB  - OBJECTIVES: In patients with a rising prostate-specific antigen (PSA) level
      during treatment with androgen deprivation therapy, identification of men who
      progress to bone metastasis and death remains problematic. Accurate risk
      stratification models are needed to better predict risk for bone metastasis and
      death among patients with castration-resistant prostate cancer (CRPC). This study
      evaluates whether alkaline phosphatase (AP) kinetics predicts bone metastasis and
      death in patients with CRPC. METHODS AND MATERIALS: A retrospective cohort study
      of 9,547 patients who underwent treatment for prostate cancer was conducted using
      the Center for Prostate Disease Research Multi-center National Database. From the
      entire cohort, 347 were found to have CRPC and, of those, 165 had 2 or more AP
      measurements during follow-up. To determine the AP velocity (APV), the slope of
      the linear regression line of all AP values was plotted over time. Rapid APV was
      defined as the uppermost quartile of APV values, which was found to be >=6.3
      IU/l/y. CRPC was defined as 2 consecutive rising PSA values after achieving a PSA
      nadir<4 ng/ml and documented testosterone values less than 50 ng/dl. The primary
      study outcomes included bone metastasis-free survival (BMFS) and overall survival
      (OS). RESULTS: Rapid APV and PSA doubling time (PSADT) less than 10 months were
      strong predictors of both BMFS and OS in a multivariable analysis. Faster PSADT
      was a stronger predictor for BMFS (odds ratio [OR] = 12.1, P<0.0001 vs. OR = 2.7,
      P = 0.011), whereas rapid APV was a stronger predictor of poorer OS (OR = 5.11, P
      = 0.0001 vs. OR = 3.98, P = 0.0034). In those with both a rapid APV and a faster
      PSADT, the odds of developing bone metastasis and death exceeded 50%. CONCLUSION:
      APV is an independent predictor of OS and BMFS in patients with CRPC. APV, in
      conjunction with PSA-based clinical parameters, may be used to better identify
      patients with CRPC who are at the highest risk of metastasis and death. These
      findings need validation in prospective studies.

PMID- 24929893
TI  - Zinc-alpha2-glycoprotein expression in adipose tissue of obese postmenopausal
      women before and after weight loss and exercise + weight loss.
AB  - OBJECTIVE: Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the
      regulation of adipose tissue metabolism due to its negative association with
      obesity and insulin resistance. The purpose of this study is to investigate the
      relationships between adipose tissue ZAG expression and central obesity, and the
      effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX
      + WL) on ZAG expression. DESIGN AND METHODS: A six-month, longitudinal study of
      33 healthy, overweight or obese postmenopausal women (BMI: 25-46 kg/m(2)) was
      conducted. Abdominal and gluteal adipose tissue samples were obtained before and
      after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR.
      RESULTS: Prior to interventions, abdominal ZAG expression was negatively
      correlated with visceral fat (r = -0.50, P < 0.005), sagittal diameter (r = 
      0.42, P < 0.05), and positively related to VO(2)max (r = 0.37, P < 0.05). Gluteal
      ZAG expression was negatively correlated with weight, fat-free mass, visceral
      fat, resting metabolic rate, and fasting insulin (r = -0.39 to -0.50, all P <
      0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after
      AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change
      significantly with AEX + WL and WL. CONCLUSIONS: Abdominal ZAG expression may be
      important in central fat accumulation and fitness but only modestly increase
      (nonsignificantly) with weight reduction alone or with aerobic training in obese
      postmenopausal women.

PMID- 24929894
TI  - Significance of plasma adiponectin for diagnosis, neurological severity and
      functional outcome in ischemic stroke - Research for Biomarkers in Ischemic
      Stroke (REBIOS).
AB  - OBJECTIVE: Although adiponectin is a major adipocytokine that affects the
      pathogenesis of various cardiovascular diseases, its clinical significance in
      stroke remains controversial. We investigated the clinical significance of plasma
      adiponectin for the diagnosis, neurological severity and functional outcomes of
      patients with ischemic stroke. METHODS: We prospectively enrolled 171 patients
      with ischemic stroke and 171 age- and sex-matched healthy controls. Blood samples
      and clinical information were obtained at day 0, 3, 7, 14 and 90 after stroke
      onset. RESULTS: Average adiponectin values at day 0 did not significantly differ
      between the controls and the patients, but were significantly lower and higher in
      patients with atherothrombotic brain (ATBI) (p=0.047) and cardioembolic (CE)
      (p=0.008) infarction, respectively, than in the controls. Multivariate logistic
      regression analyses showed that the adiponectin value at day 0 could predict ATBI
      (odds ratio, 0.75; 95% confidence interval, 0.58 to 0.91, p=0.009, per 1-MUg/mL
      increase). Adiponectin values at day 0 were positively associated with
      neurological severity as evaluated by the National Institute of Health Stroke
      Scale upon admission (r=0.420, p=0.003) and were higher in the groups with poor
      outcomes (modified Rankin Scale (mRS) >= 3 on day 90) than in those with good
      ones (mRS <= 2) in all stroke subtypes, with statistical significance in ATBI
      (p=0.015). CONCLUSIONS: Plasma adiponectin values may help to classify stroke
      subtypes and predict neurological severity and functional outcome in ischemic
      stroke patients.

PMID- 24929895
TI  - Management of clinical stage IIIA primary lung cancers in the National Cancer
      Database.
AB  - BACKGROUND: Clinical stage IIIA (cStage IIIA) non-small cell lung cancer (NSCLC)
      resulting from mediastinal lymph node disease (stage IIIA-cN2) represents one of
      the more challenging lung cancer scenarios. Not only is the prognosis
      disappointing but the accuracy of mediastinal staging is uncertain, the optimal
      treatment approach is unclear, and the outcomes are variable. In attempt to
      assess the current state of clinical stage IIIA-cN2 NSCLC in the United States,
      we examined this controversial cohort in the largest clinical database resource
      available, the National Cancer Database (NCDB). METHODS: The NCDB was queried for
      patients diagnosed between 1999 and 2011 with NSCLC, clinically staged to have
      mediastinal lymph node metastases but not systemic metastases (T1-3, N2, M0,
      cStage IIIA). RESULTS: A total of 83,913 cSstage IIIA NSCLC patients with
      presumed or confirmed mediastinal lymph node metastases were identified. Clinical
      staging of the mediastinum was variable, as lymph nodes were only biopsied in 23%
      of patients who were treated without surgery, and in surgical patients clinical
      N2 status was pathologically confirmed in only 56% of treatment naive patients.
      The most common treatment approach was nonsurgical, involving chemotherapy,
      radiation, or both (69% of patients) followed by surgery (14%). The 5-year
      survival varied by treatment and was highest for patients treated with surgery in
      combination with chemotherapy, radiation, or both (38%), followed by surgery
      alone (30%), nonsurgical treatment (11%), and worst for untreated patients (5%).
      CONCLUSIONS: There is cause for concern over the accuracy of the clinical staging
      of the mediastinum among cStage IIIA-cN2 patients in the United States. The use
      of surgery is relatively low but is associated with an encouraging 5-year
      survival. Further study is needed to clarify the accuracy of mediastinal staging
      in the United States for cStage IIIA-cN2 NSCLC.

PMID- 24929896
TI  - Testicular biochemicals, sperm reserves and daily sperm production of West
      African dwarf bucks fed varied levels of dietary aflatoxin.
AB  - An experiment was conducted with twenty West African dwarf (WAD) bucks (5-6
      months old) to assess reproductive potentials of growing WAD bucks to varied
      dietary aflatoxin of 0 MUg/kg, 50 MUg/kg, 100 MUg/kg and 150 MUg/kg containing in
      diets 1 (control) 2, 3 and 4 respectively, for a period of 12 weeks. At the end
      of the 12th week, the reproductive tracts of bucks were excised and homogenised
      in physiological saline for assessment of glucose, total protein and testosterone
      concentration, gonadal and extra gonadal sperm reserves. Results showed that
      gonadal and extra-gonadal sperm reserves of goats fed control diet (2.71*10(9)
      and 3.07*10(9) spermatozoa respectively) were superior (p<0.05) to those fed 50
      MUg/kg, 100 MUg/kg and 15 0MUg/kg [(1.59*10(9) and 2.33*10(9)), (1.09*10(9) and
      2.45*10(9)) and (1.00*10(9) and 1.41*10(9)) spermatozoa respectively]. Daily
      sperm production of bucks fed the control diet was significantly (p<0.05) higher
      (7.60*10(8) spermatozoa/testis) than those fed 50 MUg/kg (4.47*10(8)), 100 MUg/kg
      (3.07*10(8)) and 150 MUg/kg (2.80*10(8) spermatozoa/testis). Sperm production
      efficiency also follows the same trend as daily sperm production. Glucose and
      total protein concentration in the testes declined significantly as the aflatoxin
      level increases in the diets. Testosterone level was significantly lower in goats
      fed 100 MUg/kg than others. The study suggest that exposure of male goats to
      dietary aflatoxin up to 50 MUg/kg diet will reduced testicular biochemical and
      testosterone with resultant depression in sperm storage capability and daily
      sperm production in the animals.

PMID- 24929897
TI  - A protocol for species delineation of public DNA databases, applied to the
      Insecta.
AB  - Public DNA databases are composed of data from many different taxa, although the
      taxonomic annotation on sequences is not always complete, which impedes the
      utilization of mined data for species-level applications. There is much ongoing
      work on species identification and delineation based on the molecular data
      itself, although applying species clustering to whole databases requires
      consolidation of results from numerous undefined gene regions, and introduces
      significant obstacles in data organization and computational load. In the current
      paper, we demonstrate an approach for species delineation of a sequence database.
      All DNA sequences for the insects were obtained and processed. After filtration
      of duplicated data, delineation of the database into species or molecular
      operational taxonomic units (MOTUs) followed a three-step process in which (i)
      the genetic loci L are partitioned, (ii) the species S are delineated within each
      locus, then (iii) species units are matched across loci to form the matrix L * S,
      a set of global (multilocus) species units. Partitioning the database into a set
      of homologous gene fragments was achieved by Markov clustering using edge weights
      calculated from the amount of overlap between pairs of sequences, then
      delineation of species units and assignment of species names were performed for
      the set of genes necessary to capture most of the species diversity. The
      complexity of computing pairwise similarities for species clustering was
      substantial at the cytochrome oxidase subunit I locus in particular, but made
      feasible through the development of software that performs pairwise alignments
      within the taxonomic framework, while accounting for the different ranks at which
      sequences are labeled with taxonomic information. Over 24 different homologs, the
      unidentified sequences numbered approximately 194,000, containing 41,525 species
      IDs (98.7% of all found in the insect database), and were grouped into 59,173
      single-locus MOTUs by hierarchical clustering under parameters optimized
      independently for each locus. Species units from different loci were matched
      using a multipartite matching algorithm to form multilocus species units with
      minimal incongruence between loci. After matching, the insect database as
      represented by these 24 loci was found to be composed of 78,091 species units in
      total. 38,574 of these units contained only species labeled data, 34,891
      contained only unlabeled data, leaving 4,626 units composed both of labeled and
      unlabeled sequences. In addition to giving estimates of species diversity of
      sequence repositories, the protocol developed here will facilitate species-level
      applications of modern-day sequence data sets. In particular, the L * S matrix
      represents a post-taxonomic framework that can be used for species-level
      organization of metagenomic data, and incorporation of these methods into
      phylogenetic pipelines will yield matrices more representative of species
      diversity.

PMID- 24929898
TI  - Modelling competition and dispersal in a statistical phylogeographic framework.
AB  - Competition between organisms influences the processes governing the colonization
      of new habitats. As a consequence, species or populations arriving first at a
      suitable location may prevent secondary colonization. Although adaptation to
      environmental variables (e.g., temperature, altitude, etc.) is essential, the
      presence or absence of certain species at a particular location often depends on
      whether or not competing species co-occur. For example, competition is thought to
      play an important role in structuring mammalian communities assembly. It can also
      explain spatial patterns of low genetic diversity following rapid colonization
      events or the "progression rule" displayed by phylogenies of species found on
      archipelagos. Despite the potential of competition to maintain populations in
      isolation, past quantitative analyses have largely ignored it because of the
      difficulty in designing adequate methods for assessing its impact. We present
      here a new model that integrates competition and dispersal into a Bayesian
      phylogeographic framework. Extensive simulations and analysis of real data show
      that our approach clearly outperforms the traditional Mantel test for detecting
      correlation between genetic and geographic distances. But most importantly, we
      demonstrate that competition can be detected with high sensitivity and
      specificity from the phylogenetic analysis of genetic variation in space.

PMID- 24929899
TI  - Reprint of: fRMSDchiral: a novel algorithm to represent differences between
      positions of stereoisomers in complex with dissymmetric binding site.
AB  - The ability of molecules to distinguish between optical isomers is crucial for
      living systems. The change of position of one enantiomer in respect to the
      position of the second enantiomer within an asymmetric binding site may be
      analyzed on different levels. Root Mean Square Deviation (RMSD) may be used for
      such analyses with low precision. Additional fragment level variants of RMSD
      allow for more precise definition of differences in location of the main
      molecular features responsible for recognition of stereoisomers by a selector.
      Three fRMSDchiral parameters appear to be very useful to precisely quantify the
      change in orientations of stereoisomers. Proposed calculation emerges as
      interesting assistance in interpretation of consequences of formation
      differential interaction(s) responsible for a chiral recognition process. 

PMID- 24929900
TI  - Optimizing electrical impedance myography measurements by using a multifrequency
      ratio: a study in Duchenne muscular dystrophy.
AB  - OBJECTIVE: Electrical impedance myography (EIM) is an electrophysiological
      technique for neuromuscular evaluation that is impacted by subcutaneous fat (SF).
      Exploiting the differing frequency dependences of muscle and fat, we assessed a 2
      frequency EIM phase ratio in Duchenne muscular dystrophy (DMD) boys. METHODS:
      Twenty-eight DMD boys aged 2-13years underwent EIM and the 6-minute walk test
      (6MWT). For each subject, 50kHz phase data was input into the numerator while 20
      500kHz phase values were input into the denominator. We then performed
      correlation analyses seeking to identify the denominator frequency that
      simultaneously optimized SF and 6MWT correlations. This optimized ratio was then
      tested in 24 healthy boys. RESULTS: 50kHz phase correlated to 6MWT in DMD boys
      with R=0.52, p=0.0066, and to SF thickness with R=-0.67, p<0.001. An optimized
      ratio of 50/200kHz phase reduced the correlation of SF thickness to R=-0.075,
      p=0.45 while improving the relationship to the 6MWT (R=0.60, p=0.001). In normal
      subjects, the optimization decreased SF correlation from R=0.61 from R=0.16 with
      6MWT correlation remaining unchanged. CONCLUSIONS: The 50/200kHz EIM phase ratio
      removes the impact of SF while maintaining EIM's association with function.
      SIGNIFICANCE: The use of a phase ratio may enhance EIM's application for
      evaluation of neuromuscular disease.

PMID- 24929901
TI  - Cortical EEG alpha rhythms reflect task-specific somatosensory and motor
      interactions in humans.
AB  - Anticipating sensorimotor events allows adaptive reactions to environment with
      crucial implications for self-protection and survival. Here we review several
      studies of our group that aimed to test the hypothesis that the cortical
      processes preparing the elaboration of sensorimotor interaction is reflected by
      the reduction of anticipatory electroencephalographic alpha power (about 8-12Hz;
      event-related desynchronization, ERD), as an index that regulate task-specific
      sensorimotor processes, accounted by high-alpha sub-band (10-12Hz), rather than a
      general tonic alertness, accounted by low-alpha sub-band (8-10Hz). In this line,
      we propose a model for human cortical processes anticipating warned sensorimotor
      interactions. Overall, we reported a stronger high-alpha ERD before painful than
      non-painful somatosensory stimuli that is also predictive of the subjective
      evaluation of pain intensity. Furthermore, we showed that anticipatory high-alpha
      ERD increased before sensorimotor interactions between non-painful or painful
      stimuli and motor demands involving opposite hands. In contrast, sensorimotor
      interactions between painful somatosensory and sensorimotor demands involving the
      same hand decreased anticipatory high-alpha ERD, due to a sort of sensorimotor
      "gating" effect. In conclusion, we suggest that anticipatory cortical high-alpha
      rhythms reflect the central interference and/or integration of ascending
      (sensory) and descending (motor) signals relative to one or two hands before non
      painful and painful sensorimotor interactions. 

PMID- 24929902
TI  - Rhythmic entrainment of slow brain activity preceding leg movements.
AB  - OBJECTIVE: The time course of the contingent negative variation (CNV) as well as
      beta-power are known to entrain to regular task rhythms, revealing implicit
      anticipatory timing. Thus far, these effects have been established for manual
      responses only. Here we investigate entrainment preceding leg movements. METHODS:
      High-density EEG was recorded while participants were standing and responded to
      series of rhythmically presented arrow stimuli by making brisk leg movements. The
      standard interval between reaction stimuli differed between series and was either
      1500 or 2000 ms. Each series' final interval was 1750 ms, representing a timing
      perturbation. RESULTS: Entrainment was manifested in the CNV time course, where
      the maximum amplitude was reached just before the next stimulus was presented.
      The pattern of beta-(de)synchronization similarly entrained to the task rhythm.
      CNV scalp topographies suggested effector dependency of the entrainment-induced
      CNV. CONCLUSION: We demonstrate that lower limb motor control, like upper limb
      control, readily entrains to a regular task rhythm. SIGNIFICANCE: These findings
      are relevant to Parkinson's disease (PD), where problems are found in rhythm
      processing and temporal preparation. Investigation of the neural correlates of
      leg movement entrainment is important in view of presumed relations between
      entrainment and cueing of gait in PD.

PMID- 24929903
TI  - Reframing seizure prediction.

PMID- 24929904
TI  - P2Y1 and P2Y12 receptors in hypoxia- and adenosine diphosphate-induced pulmonary
      vasoconstriction in vivo in the pig.
AB  - PURPOSE: To investigate the role of P2Y1 and P2Y12 receptors in hypoxia- and
      adenosine diphosphate (ADP)-induced pulmonary vasoconstriction. METHODS: 19
      anaesthetized, mechanically ventilated pigs (31.3 +/- 0.7 kg) were evaluated in
      normoxia and hypoxia, without (n = 6) or with P2Y1 receptor antagonist MRS2500 (n
      = 7) or P2Y12 receptor antagonist cangrelor (n = 6) treatment. 12 pigs (29.3 +/-
      0.4 kg) were evaluated before and during ADP infusion, without and with MRS2500
      (n = 6) or cangrelor (n = 6) pre-treatment. RESULTS: Hypoxia increased (p < 0.05)
      mean pulmonary artery pressure (MPAP) by 14.2 +/- 1.1 mmHg and pulmonary vascular
      resistance (PVR) by 2.7 +/- 0.4 WU. Without treatment MPAP and PVR remained
      unaltered (p = ns) for 90 min hypoxia. During hypoxia MRS2500 decreased (p <
      0.013) MPAP by 4.3 +/- 1.2 mmHg within 15 min. Cangrelor decreased (p < 0.036)
      MPAP to be 3.3 +/- 0.4 and 3.6 +/- 0.6 mmHg lower than hypoxia baseline after 10
      and 30 min. PVR was, however, unaltered (p = ns) by MRS2500 or cangrelor during
      hypoxia. ADP increased (p < 0.001) MPAP and PVR to stabilize 11.1 +/- 1.3 mmHg
      and 2.7 +/- 0.3 WU higher than baseline. MRS2500 or cangrelor pre-treatment
      totally abolished the sustained MPAP- and PVR-increases to ADP. CONCLUSIONS: ADP
      elicits pulmonary vasoconstriction through P2Y1 and P2Y12 receptor activation.
      ADP is not a mandatory modulator, but may still contribute to pulmonary vascular
      tone during acute hypoxia. Further investigations into the mechanisms behind ADP
      induced pulmonary vasoconstriction and the role of ADP as a modulator of
      pulmonary vascular tone during hypoxia are warranted.

PMID- 24929905
TI  - Management of neonatal proptosis: a systematic review.
AB  - Gross proptosis presenting at birth is an uncommon manifestation of a variety of
      lesions that can compromise vision and result in disfigurement or even loss of
      life. Notably, many disease entities have different presentations and prognoses
      in neonates compared to older children. A structured mental framework is
      essential to an efficient and coordinated response. We present three challenging
      cases of neonatal proptosis and discuss the clinical presentation and biological
      behavior of the lesions that are most often implicated. 

PMID- 24929906
TI  - Epidemiology of pediatric ocular trauma admissions.

PMID- 24929907
TI  - Authors' response.

PMID- 24929908
TI  - Synthetic oligonucleotide separations by mixed-mode reversed-phase/weak anion
      exchange liquid chromatography.
AB  - Synthetic oligonucleotides gain increasing importance in new therapeutic concepts
      and as probes in biological sciences. If pharmaceutical-grade purities are
      required, chromatographic purification using ion-pair reversed-phase
      chromatography is commonly carried out. However, separation selectivity for
      structurally closely related impurities is often insufficient, especially at high
      sample loads. In this study, a "mixed-mode" reversed-phase/weak anion exchanger
      stationary phase has been investigated as an alternative tool for chromatographic
      separation of synthetic oligonucleotides with minor sequence variations. The
      employed mixed-mode phase shows great flexibility in method development. It has
      been run in various gradient elution modes, viz. one, two or three parameter
      (mixed) gradients (altering buffer pH, buffer concentration, and organic
      modifier) to find optimal elution conditions and gain further insight into
      retention mechanisms. Compared to ion-pair reversed-phase and mere anion-exchange
      separation, enhanced selectivities were observed with the mixed-mode phase for 20
      23 nucleotide (nt) long oligonucleotides with similar sequences. Oligonucleotides
      differing by 1, 2 or 3 nucleotides in length could be readily resolved and
      separation factors for single nucleotide replacements declined in the order
      Cytosine (C)/Guanine (G)>Adenine (A)/Guanine~Guanine/Thymine
      (T)>Adenine/Cytosine~Cytosine/Thymine>Adenine/Thymine. Selectivities were larger
      when the modification was at the 3' terminal-end, declined when it was in the
      middle of the sequence and was smallest when it was located at the 5' terminus.
      Due to the lower surface area of the 200A pore size mixed-mode stationary phase
      compared to the corresponding 100A material, lower retention times with equal
      selectivities under milder elution conditions were achievable. Considering high
      sample loading capacities of the mixed-mode anion-exchanger phase, it should have
      great potential for chromatographic oligonucleotide separation and purification. 

PMID- 24929909
TI  - Assessment of a new method for the analysis of decomposition gases of polymers by
      a combining thermogravimetric solid-phase extraction and thermal desorption gas
      chromatography mass spectrometry.
AB  - For analysis of the gaseous thermal decomposition products of polymers, the
      common techniques are thermogravimetry, combined with Fourier transformed
      infrared spectroscopy (TGA-FTIR) and mass spectrometry (TGA-MS). These methods
      offer a simple approach to the decomposition mechanism, especially for small
      decomposition molecules. Complex spectra of gaseous mixtures are very often hard
      to identify because of overlapping signals. In this paper a new method is
      described to adsorb the decomposition products during controlled conditions in
      TGA on solid-phase extraction (SPE) material: twisters. Subsequently the twisters
      were analysed with thermal desorption gas chromatography mass spectrometry (TDS
      GC-MS), which allows the decomposition products to be separated and identified
      using an MS library. The thermoplastics polyamide 66 (PA 66) and polybutylene
      terephthalate (PBT) were used as example polymers. The influence of the sample
      mass and of the purge gas flow during the decomposition process was investigated
      in TGA. The advantages and limitations of the method were presented in comparison
      to the common analysis techniques, TGA-FTIR and TGA-MS. 

PMID- 24929910
TI  - Single "click" synthesis of a mixed-mode silica sorbent and application in matrix
      solid-phase dispersion extraction of beta-agonists from porcine liver.
AB  - A single "click" strategy is proposed for the preparation of a reversed
      phase/weak cation-exchange mixed-mode silica-based sorbent (silica-WCX). Upon
      this strategy, both 1-dodecyne and 5-hexynoic acid were simultaneously
      immobilized onto azide-silica in varied ratio via Cu (I)-catalyzed azide-alkyne
      cycloaddition click reaction. The chemical compositions of silica-WCXs were
      characterized by elemental analysis, acid-base titration and Fourier transform
      infrared spectroscopy. The results indicated that the actual mole ratio of n
      dodecyl to carboxylic group on the sorbent is almost the same as the reactant
      ratio of 1-dodecyne to 5-hexynoic acid, and the repeatability of synthesis method
      is good. After that, two beta-agonists, clenbuterol and ractopamine, were
      selected as model drug residues to evaluate the applicability of silica-WCX in
      matrix solid-phase dispersion extraction for the determination of basic drug
      residues in porcine liver by HPLC/UV. In comparison with some commercial
      sorbents, silica-WCX exhibited higher recoveries and better purification
      capability. Under the optimized conditions, linearity ranges were between 0.04
      and 8.0MUg/g for both analytes with coefficients of determination (R(2)) higher
      than 0.9997. The average recoveries at three spiked levels ranged from 92.5% to
      105.0% with RSDs less than 6.6%. 

PMID- 24929911
TI  - Role of urea on recombinant Apo A-I stability and its utilization in anion
      exchange chromatography.
AB  - Apolipoprotein A-I (Apo A-I) is an important lipid-binding protein involved in
      the transport and metabolism of cholesterol. High protein purity, in particular
      with respect to endotoxins is required for therapeutic applications. The use of
      urea during the purification process of recombinant Apo A-I produced in
      Escherichia coli has been suggested so as to provide high endotoxin clearance. In
      this work, we show that urea can be used as a sole modifier during the ion
      exchange chromatographic purification of Apo A-I and we investigate the molecular
      mechanism of elution by correlating the effect of urea on self-association,
      conformation and adsorption equilibrium properties of a modified model Apo A-I.
      In the absence of urea the protein was found to be present as a population of
      oligomers represented mainly by trimers, hexamers and nonamers. The addition of
      urea induced oligomer dissociation and protein structure unfolding. We correlated
      the changes in protein association and conformation with variations of the
      adsorption equilibrium of the protein on a strong anion exchanger. It was
      confirmed that the adsorption isotherms, described by a Langmuir model, were
      dependent on both protein and urea concentrations. Monomers, observed at low urea
      concentration (0.5M), were characterized by larger binding affinity and
      adsorption capacity compared to both protein oligomers (0M) and unfolded monomers
      (2-8M). The reduction of both the binding strength and maximum adsorption
      capacity at urea concentrations larger than 0.5M explains the ability of urea of
      inducing elution of the protein from the ion exchange resin. The dissociation of
      the protein complexes occurring during the elution could likely be the origin of
      the effective clearance of endotoxins originally trapped inside the oligomers. 

PMID- 24929912
TI  - Subventricular spread of diffuse intrinsic pontine glioma.

PMID- 24929913
TI  - Cross-cultural adaptation of a patient-based tool for evaluating the
      implementation of patient education in acute care settings.
AB  - OBJECTIVE: The purpose was cross-cultural adaptation, validation, and
      psychometric analysis of an originally Norwegian patient-based tool measuring the
      patient education practices of the nurses. METHODS: Systematic translation and
      validation of the Patient Information and Nurse Interaction (PINI) scale was
      performed. Exploratory factor analysis of the modified Persian version was
      conducted using a sample consisting of 163 Persian-speaking patients discharging
      from a neurosurgery unit. RESULTS: The scale included three factors, cumulatively
      accounting for 61% of the variance. The first factor with seven items reflected
      "providing information on treatment and care plans". The second and the third
      factors each contained four items and reflected "nurses' interactions with the
      clients" and "providing advice on care after discharge", respectively. Alpha
      coefficients were 0.90 for the overall scale, 0.87 for the first, 0.77 for the
      second, and 0.88 for the third subscale. CONCLUSION: The study supported that the
      modified scale had good psychometric properties measuring three major components
      including providing information, interaction with the client, and providing
      advice about post-discharge care. PRACTICE IMPLICATIONS: It seems that the
      modified version of the PINI scale can provide sound assessment of the
      implementation of patient education in a different acute care setting with a new
      language and culture.

PMID- 24929914
TI  - Protein quantitation by complexation of fluorescent tetraphenylthiophene cation
      to anion-terminated poly(N-isopropylacrylamide): aggregation-enhanced emission
      and electrostatic interaction.
AB  - A fluorescent biological sensor utilizing aggregation-enhanced emission (AEE)
      property was developed in our laboratory. First, the AEE-active fluorescent
      tetraphenylthiophene (TP) unit was synthetically connected to poly(N
      isopropylacrylamide) by covalent and ionic bonds, resulting in the respective c-
      and i-TP-PNIPAM for the detection and quantification of the bovine serum albumin
      (BSA) model protein. When bind to BSA, the ionic i-TP-PNIPAM shows much better
      fluorescence (FL) sensitivity compared to c-PNIPAM. The fluorescence (FL)
      intensity of i-TP-PNIAPM displays a good linear dependence on concentration of
      BSA (0-1 mg/mL), indicating quantitative fluorimetric protein detection can be
      achieved. Further addition of anionic surfactant of sodium dodecylsulfate (SDS)
      considerably raised the FL intensity of the complex solution. All the FL response
      was discussed in term of conformational freedom of the TP unit under different
      environmental constraints.

PMID- 24929915
TI  - Understanding the formation and influence of attitudes in patients' treatment
      choices for lower back pain: testing the benefits of a hybrid choice model
      approach.
AB  - A growing number of studies across different fields are making use of a new class
      of choice models, labelled variably as hybrid model structures or integrated
      choice and latent variable models, and incorporating the role of attitudes in
      decision making. To date, this technique has not been used in health economics.
      The present paper looks at the formation of such attitudes and their role in
      patients' treatment choices in the context of low back pain. We use stated choice
      data collected from a sample of 561 patients with 348 respondents referred to a
      regional spine centre in Middelfart, Denmark in spring/summer 2012. We show how
      the hybrid model structure is able to make a link between attitudinal questions
      and treatment choices, and also explains variation of these attitudes across key
      socio-demographic groups. However, we also show how, in this case, only a small
      share of the overall heterogeneity is linked to the latent attitude construct.
      Despite their growing popularity, the key findings of the advanced model, despite
      a greater insight into the drivers of attitudes and small gains in efficiency,
      are no different from standard approaches which remain easier to apply. 

PMID- 24929916
TI  - A changing epidemiology of suicide? The influence of birth cohorts on suicide
      rates in the United States.
AB  - The increases in suicide among middle-aged baby boomers (born between 1946 and
      1964) in the United States since 1999 suggest a changing epidemiology of suicide.
      Using data from 1935 to 2010, this paper conducts age-period-cohort analyses to
      determine the impact of cohorts in shaping temporal patterns of suicide in the
      United States. The analysis demonstrates that age, period and cohort effects are
      all important in determining suicide trends. Net of age and period effects, the
      cohort pattern of suicide rates is U-shaped, with cohorts born between 1915 and
      1945 possessing among the very lowest suicide rates. Suicide rates begin to rise
      with boomers and subsequent cohorts exhibit increasingly higher rates of suicide.
      The general pattern exists for both men and women but is especially pronounced
      among males. The average suicide rate over the entire period for males is about
      28 per 100,000, 95% CI [27.4, 28.7]. For males born in 1930-34, the suicide rate
      is estimated to be 17.4 per 100,000, 95% CI [15.9, 18.8]; for males born between
      1955 and 1959, the rate is essentially the same as the average for the period
      while for males born between 1985 and 1989, the suicide rate is estimated to be
      37.8 per 100,000, 95% CI [33.1, 43.4]. The results dispute popular claims that
      boomers exhibit an elevated suicide rate relative to other generations, but
      boomers do appear to have ushered in new cohort patterns of suicide rates over
      the life course. These patterns are interpreted within a Durkheimian framework
      that suggests weakened forms of social integration and regulation among postwar
      cohorts may be producing increased suicide rates. 

PMID- 24929917
TI  - Why do some countries spend more for health? An assessment of sociopolitical
      determinants and international aid for government health expenditures.
AB  - A consensus exists that rising income levels and technological development are
      among key drivers of total health spending. Determinants of public sector health
      expenditure, by contrast, are less well understood. This study examines a complex
      relationship across government health expenditure (GHE), sociopolitical risks,
      and international aid, while taking into account the impacts of national income,
      debt and tax financing and aging populations on health spending. We apply a fixed
      effects two-stage least squares regression method to a panel dataset comprising
      120 countries for the years 1995 through 2010. Our results show that democratic
      accountability has a diminishing positive correlation with GHE, and that levels
      of GHE are higher when government is more stable. Corruption is associated with
      less GHE in developing countries, but with higher GHE in developed countries. We
      also find that development assistance for health (DAH) is fungible with
      domestically financed government health expenditure (DGHE). For an average
      country, a 1% increase in DAH to government is associated with a 0.03-0.04%
      decrease in DGHE. Furthermore, the degree of fungibility of DAH to government is
      higher in countries where corruption or ethnic tensions are widespread. However,
      DAH to non-governmental organizations is not fungible with DGHE. 

PMID- 24929919
TI  - Translating an ACGME-required Practice Quality Improvement project into
      preparation for the Maintenance of Certification Part IV.

PMID- 24929918
TI  - The influence of women's empowerment on maternal health care utilization:
      evidence from Albania.
AB  - Women in Albania receive antenatal care and postnatal care at lower levels than
      in other countries in Europe. Moreover, there are large socio-economic and
      regional disparities in maternal health care use. Previous research in low- and
      middle-income countries has found that women's status within the household can be
      a powerful force for improving the health, longevity, and mental and physical
      capacity of mothers and the well-being of children, but there is very little
      research on this issue in the Balkans. The aim of this paper is to investigate
      the influence of women's empowerment within the household on antenatal and
      postnatal care utilization in Albania. The research questions are explored
      through the use of bivariate and multivariate analyses based on nationally
      representative data from the 2008-09 Albania Demographic and Health Survey. The
      linkages between women's empowerment and maternal health care utilization are
      analyzed using two types of indicators of women's empowerment: decision making
      power and attitudes toward domestic violence. The outcome variables are
      indicators of the utilization of antenatal care and postnatal care. The findings
      suggest that use of maternal health care services is influenced by women's roles
      in decision-making and the attitudes of women towards domestic violence, after
      controlling for a number of socio-economic and demographic factors which are
      organized at individual, household, and community level. The study results
      suggest that policy actions that increase women's empowerment at home could be
      effective in helping assure good maternal health. 

PMID- 24929920
TI  - An integrative method to normalize RNA-Seq data.
AB  - BACKGROUND: Transcriptome sequencing is a powerful tool for measuring gene
      expression, but as well as some other technologies, various artifacts and biases
      affect the quantification. In order to correct some of them, several
      normalization approaches have emerged, differing both in the statistical strategy
      employed and in the type of corrected biases. However, there is no clear standard
      normalization method. RESULTS: We present a novel methodology to normalize RNA
      Seq data, taking into account transcript size, GC content, and sequencing depth,
      which are the major quantification-related biases. In this study, we found that
      transcripts shorter than 600 bp have an underestimated expression level, while
      longer transcripts are even more overestimated that they are long. Second, it was
      well known that the higher the GC content (>50%), the more the transcripts are
      underestimated. Third, we demonstrated that the sequencing depth impacts the size
      bias and proposed a correction allowing the comparison of expression levels among
      many samples. The efficiency of our approach was then tested by comparing the
      correlation between normalized RNA-Seq data and qRT-PCR expression measurements.
      All the steps are automated in a program written in Perl and available on
      request. CONCLUSIONS: The methodology presented in this article identifies and
      corrects different biases that influence RNA-Seq quantification, and provides
      more accurate estimations of gene expression levels. This method can be applied
      to compare expression quantifications from many samples, but preferentially from
      the same tissue. In order to compare samples from different tissue, a calibration
      using several reference genes will be required.

PMID- 24929921
TI  - Fatal acute pulmonary oedema and acute renal failure following multiple
      wasp/hornet (Vespa affinis) stings in Sri Lanka: two case reports.
AB  - INTRODUCTION: Vespa affinis is a hornet widely distributed in Sri Lanka and it is
      responsible for the highest number of deaths related to Hymenoptera stings. Apart
      from the early reactions, victims often die in hospital many hours later due to
      complications such as myocardial infarction and multiple organ failure. Increased
      microvascular permeability and acute pulmonary oedema as the primary pathology is
      less known in hornet envenoming. CASE PRESENTATION: Here, we report clinical and
      postmortem findings of two Sinhalese patients, a 48-year-old husband and his 46
      year-old wife, who both died following a massive attack by hornets 32 hours and 9
      hours after the incidence respectively. At postmortem examination, both patients
      had pleural effusions, acute pulmonary oedema and red cell casts in their urine.
      Their coronary arteries and histology of myocardium were normal. CONCLUSION:
      Early recognition of acute pulmonary oedema in hornet stings is needed with
      implementation of crucial treatments to avert deaths.

PMID- 24929922
TI  - Intramucosal adenocarcinoma arising from ectopic gastric mucosa in the upper
      esophagus treated successfully with endoscopic mucosal resection.

PMID- 24929923
TI  - Novel field emission SEM column with beam deceleration technology.
AB  - A novel field-emission SEM column has been developed that features Beam
      Deceleration Mode, high-probe current and ultra-fast scanning. New detection
      system in the column is introduced to detect true secondary electron signal. The
      resolution power at low energy was doubled for conventional SEM optics and
      moderately improved for immersion optics. Application examples at low landing
      energies include change of contrast, imaging of non-conductive samples and thin
      layers. 

PMID- 24929924
TI  - Analysis of electron beam damage of exfoliated MoS2 sheets and quantitative HAADF
      STEM imaging.
AB  - In this work we examined MoS2 sheets by aberration-corrected scanning
      transmission electron microscopy (STEM) at three different energies: 80, 120 and
      200 kV. Structural damage of the MoS2 sheets has been controlled at 80 kV
      according a theoretical calculation based on the inelastic scattering of the
      electrons involved in the interaction electron-matter. The threshold energy for
      the MoS2 material has been found and experimentally verified in the microscope.
      At energies higher than the energy threshold we show surface and edge defects
      produced by the electron beam irradiation. Quantitative analysis at atomic level
      in the images obtained at 80 kV has been performed using the experimental images
      and via STEM simulations using SICSTEM software to determine the exact number of
      MoS22 layers.

PMID- 24929925
TI  - Dengue outlook for the World Cup in Brazil.

PMID- 24929926
TI  - Short-term cognitive-behavioral therapy for binge eating disorder: long-term
      efficacy and predictors of long-term treatment success.
AB  - The present study evaluates the long-term efficacy (four years after treatment)
      of a short-term Cognitive-Behavioral Treatment (CBT) of Binge Eating Disorder
      (BED). We examined patient characteristics, mostly measured at the end of
      treatment, for their predictive value of long-term success. Forty-one BED
      patients between 18 and 70 years took part in a randomized controlled trial (RCT)
      for a short-term treatment and were evaluated until 4 years after treatment.
      Assessments comprised structured interviews on comorbid mental disorder/eating
      disorder pathology and questionnaires on eating disorder pathology/general
      psychopathology. BED core symptoms and associated psychopathology improved
      substantially during treatment phase and further improved or at least remained
      stable during the follow-up period. End of treatment predictors for long term
      success were elevated weight and eating concern and higher frequency of objective
      binges. Tailoring additional interventions to patients' individual needs could
      further improve treatment efficacy. 

PMID- 24929927
TI  - Self-compassion as an emotion regulation strategy in major depressive disorder.
AB  - Cognitive reappraisal and acceptance are two presumably adaptive emotion
      regulation strategies in depression. More recently, self-compassion has been
      discussed as another potentially effective strategy for coping with depression.
      In the present study, we compared the effectiveness of self-compassion with a
      waiting condition, reappraisal, and acceptance in a clinically depressed sample,
      and tested the hypothesis that the intensity of depressed mood would moderate the
      differential efficacy of these strategies. In an experimental design, we induced
      depressed mood at four points in time in 48 participants meeting criteria for
      major depressive disorder. After each mood induction, participants were
      instructed to wait, reappraise the situation, accept their negative emotions, or
      employ self-compassion to regulate their depressed mood. Self-ratings of
      depressed mood were assessed before and after each mood induction and regulation
      phase. Results showed that the reduction of depressed mood was significantly
      greater in the self-compassion condition than in the waiting condition. No
      significant differences were observed between the self-compassion and the
      reappraisal condition, and between the self-compassion and the acceptance
      condition in patients' mood ratings. However, the intensity of self-rated
      depressed mood at baseline was found to moderate the comparative effectiveness of
      self-compassion and reappraisal with a trend of self-compassion being more
      effective than reappraisal in high depressed mood at baseline. These findings
      support the use of self-compassion as another adaptive emotion regulation
      strategy for patients with major depressive disorder, especially for those
      suffering from high levels of depressed mood. 

PMID- 24929928
TI  - The 1-2-3 Magic parenting program and its effect on child problem behaviors and
      dysfunctional parenting: a randomized controlled trial.
AB  - This study investigated the effectiveness of the 1-2-3 Magic parenting program, a
      brief cognitive-behavioral program, when delivered to large groups of caregivers.
      The effectiveness of two versions of the programs in reducing child problem
      behaviors and dysfunctional parenting, and the effect on emotion-related
      parenting style, were examined. Ninety-two participants with 2-12-year-old
      children were randomly assigned to one of three groups: DVD (n = 31); Emotion
      coaching (EC) (n = 31); or Waitlist-control (n = 30). Both intervention groups
      reported significantly decreased child problem behaviors, dysfunctional
      parenting, parental depression and parental stress at post-intervention as
      compared to the control group. Additionally, the DVD group reported decreased
      parental anxiety, and the EC group reported a decrease in emotion-dismissing
      parenting style. Emotion-coaching parenting style remained unchanged for all
      groups at post-intervention. The results were maintained after three months.
      After two years, all intervention effects were maintained for the DVD group. For
      the EC group, effects were maintained on the main outcome variables. The results
      suggest that both 1-2-3 Magic programs are effective at reducing child problem
      behavior and dysfunctional parenting when delivered to large groups of
      caregivers, and that both programs are suitable for a broad delivery approach. 

PMID- 24929929
TI  - Technical- and environmental-efficiency analysis of irrigated cotton-cropping
      systems in Punjab, Pakistan using data envelopment analysis.
AB  - Cotton cropping in Pakistan uses substantial quantities of resources and
      adversely affects the environment with pollutants from the inputs, particularly
      pesticides. A question remains regarding to what extent the reduction of such
      environmental impact is possible without compromising the farmers' income. This
      paper investigates the environmental, technical, and economic performances of
      selected irrigated cotton-cropping systems in Punjab to quantify the
      sustainability of cotton farming and reveal options for improvement. Using mostly
      primary data, our study quantifies the technical, cost, and environmental
      efficiencies of different farm sizes. A set of indicators has been computed to
      reflect these three domains of efficiency using the data envelopment analysis
      technique. The results indicate that farmers are broadly environmentally
      inefficient; which primarily results from poor technical inefficiency. Based on
      an improved input mix, the average potential environmental impact reduction for
      small, medium, and large farms is 9, 13, and 11 %, respectively, without
      compromising the economic return. Moreover, the differences in technical, cost,
      and environmental efficiencies between small and medium and small and large farm
      sizes were statistically significant. The second-stage regression analysis
      identifies that the entire farm size significantly affects the efficiencies,
      whereas exposure to extension and training has positive effects, and the sowing
      methods significantly affect the technical and environmental efficiencies.
      Paradoxically, the formal education level is determined to affect the
      efficiencies negatively. This paper discusses policy interventions that can
      improve the technical efficiency to ultimately increase the environmental
      efficiency and reduce the farmers' operating costs. 

PMID- 24929930
TI  - The laryngeal motor cortex: its organization and connectivity.
AB  - Our ability to learn and control the motor aspects of complex laryngeal
      behaviors, such as speech and song, is modulated by the laryngeal motor cortex
      (LMC), which is situated in the area 4 of the primary motor cortex and
      establishes both direct and indirect connections with laryngeal motoneurons. In
      contrast, the LMC in monkeys is located in the area 6 of the premotor cortex,
      projects only indirectly to laryngeal motoneurons and its destruction has
      essentially no effect on production of species-specific calls. These differences
      in cytoarchitectonic location and connectivity may be a result of hominid
      evolution that led to the LMC shift from the phylogenetically 'old' to 'new'
      motor cortex in order to fulfill its paramount function, that is, voluntary motor
      control of human speech and song production. 

PMID- 24929932
TI  - Actibacterium atlanticum sp. nov., isolated from surface seawater of the Atlantic
      Ocean.
AB  - A taxonomic study was carried out on strain 22II-S11-z10(T), which was isolated
      from the surface seawater of the Atlantic Ocean. The bacterium was found to be
      Gram-stain negative, oxidase and catalase positive, oval- to rod-shaped and non
      motile. Growth was observed at salinities of 0.5-9 % and at temperatures of 10-41
      degrees C. The isolate can reduce nitrate to nitrite, degrade gelatin and
      aesculin, but can not degrade Tween 80. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that strain 22II-S11-z10(T) belongs to the genus
      Actibacterium, with the highest sequence similarity to the type strain
      Actibacterium mucosum CECT 7668(T) (97.3 %). The DNA-DNA hybridization estimate
      value between strain 22II-S11-z10(T) and A. mucosum CECT 7668(T) was 19.30 +/-
      2.29 %. The principal fatty acids were identified as Summed Feature 8 (C18:1
      omega7c/omega6c as defined by the MIDI system, 75.2 %) and Summed Feature 3
      (C16:1 omega7c/omega6c, 6.9 %). The G+C content of the chromosomal DNA was
      determined to be 59.0 mol%. The respiratory quinone was determined to be Q-10
      (100 %). Phosphatidylglycerol, phosphatidylcholine, two phospholipids, two
      aminolipids and two lipids were identified in the polar lipids. The combined
      genotypic and phenotypic data show that strain 22II-S11-z10(T) represents a novel
      species within the genus Actibacterium, for which the name Actibacterium
      atlanticum sp. nov. is proposed, with the type strain 22II-S11-z10(T) (=MCCC
      1A09298(T) = LMG 27158(T)). 

PMID- 24929931
TI  - Hirano bodies differentially modulate cell death induced by tau and the amyloid
      precursor protein intracellular domain.
AB  - BACKGROUND: Hirano bodies are actin-rich paracrystalline inclusions found in
      brains of patients with Alzheimer's disease (AD), frontotemporal dementia (FTD),
      and in normal aged individuals. Although studies of post-mortem brain tissue
      provide clues of etiology, the physiological function of Hirano bodies remains
      unknown. A cell culture model was utilized to study the interactions of mutant
      tau proteins, model Hirano bodies, and GSK3beta in human astrocytoma cells.
      RESULTS: Most tau variants showed co-localization with model Hirano bodies.
      Cosedimentation assays revealed this interaction may be direct, as recombinant
      purified forms of tau are all capable of binding F-actin. Model Hirano bodies had
      no effect or enhanced cell death induced by tau in the absence of amyloid
      precursor protein intracellular domain (AICD). In the presence of AICD and tau,
      synergistic cell death was observed in most cases, and model Hirano bodies
      decreased this synergistic cell death, except for forms of tau that caused
      significant cell death in the presence of Hirano bodies only. A role for the
      kinase GSK3beta is suggested by the finding that a dominant negative form of
      GSK3beta reduces this synergistic cell death. A subset of Hirano bodies in brain
      tissue of both Alzheimer's disease and normal aged individuals was found to
      contain tau, with some Hirano bodies in Alzheimer's disease brains containing
      hyperphosphorylated tau. CONCLUSION: The results demonstrate a complex
      interaction between tau and AICD involving activation of GSK3beta in promoting
      cell death, and the ability of Hirano bodies to modulate this process.

PMID- 24929933
TI  - Flavimarina pacifica gen. nov., sp. nov., a new marine bacterium of the family
      Flavobacteriaceae, and emended descriptions of the genus Leeuwenhoekiella,
      Leeuwenhoekiella aequorea and Leeuwenhoekiella marinoflava.
AB  - A facultatively anaerobic, Gram-stain negative, rod-shaped and yellow pigmented
      bacterium, designated strain IDSW-73(T), was isolated from a seawater sample and
      subjected to a polyphasic taxonomic study. Phylogenetic analysis based on 16S
      rRNA gene sequences revealed that the novel strain formed a distinct phyletic
      line in the family Flavobacteriaceae and is most closely related to the members
      of the genus Leeuwenhoekiella, with 16S rRNA gene sequence similarity of 91.4
      92.6 %. Strain IDSW-73(T) was found to be able to grow with 0-12 % NaCl and at 4
      33  degrees C; and was able to hydrolyse gelatin, starch and Tweens 20, 40 and
      80. The DNA G+C content was determined to be 42.2 mol%. The predominant cellular
      fatty acids were identified as branched-chain saturated and unsaturated and
      straight-chain unsaturated fatty acids such as iso-C15:0, iso-C15:1, iso-C17:1
      omega9c, C15:1 omega6c, iso-C15:0 3-OH, iso-C17:0 3-OH and summed feature 3 (as
      defined by MIDI), comprising iso-C15:0 2-OH and/or C16:1 omega7c. The polar
      lipids found were phosphatidylethanolamine, two unknown aminolipids and one
      unknown lipid. The major respiratory quinone was identified as MK-6. The
      significant molecular distinctiveness between the novel isolate and its nearest
      neighbours were strongly supported by notable differences in physiological and
      biochemical tests. Therefore, strain IDSW-73(T) is considered to represent a
      novel genus and species within the family Flavobacteriaceae, for which the name
      Flavimarina pacifica gen. nov., sp. nov. is proposed. The type strain is IDSW
      73(T) (=KCTC 32466(T) = KMM 6759(T)). Emended descriptions of the recognized
      species of the genus Leeuwenhoekiella are also proposed.

PMID- 24929934
TI  - The effect of experience on perceptual spaces when judging synthesized voice
      quality: a multidimensional scaling study.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to determine the effect of
      experience on the perceptual space of listeners when judging voice quality. STUDY
      DESIGN: This was a within-subjects group design. METHOD: Speech-language
      pathologists, singing voice teachers, speech-language pathology graduate students
      with and without experience with a voice client, graduate students who have
      completed a voice pedagogy course, and inexperienced served as listeners. Each
      participant rated the similarity of pairs of synthesized stimuli with
      systematically altered measurements of jitter, shimmer, and noise-to-harmonics
      ratio on a visual analog scale ranging from no similarity to extremely similar.
      RESULTS: Results showed that participants with different levels and types of
      experience used different perceptual spaces (of additive noise and perturbation
      measures) when judging the similarity of stimulus pairs. CONCLUSION: The
      conclusion was that perceptual spaces differ among individuals with different
      levels and types of experience when judging the similarity of pairs of stimuli
      with systematically altered acoustical measurements.

PMID- 24929935
TI  - Voice disorders in teachers. A review.
AB  - INTRODUCTION: Voice disorders are very prevalent among teachers and consequences
      are serious. Although the literature is extensive, there are differences in the
      concepts and methodology related to voice problems; most studies are restricted
      to analyzing the responses of teachers to questionnaires and only a few studies
      include vocal assessments and videolaryngoscopic examinations to obtain a
      definitive diagnosis. OBJECTIVE: To review demographic studies related to vocal
      disorders in teachers to analyze the diverse methodologies, the prevalence rates
      pointed out by the authors, the main risk factors, the most prevalent laryngeal
      lesions, and the repercussions of dysphonias on professional activities.
      MATERIALS AND METHODS: The available literature (from 1997 to 2013) was
      narratively reviewed based on Medline, PubMed, Lilacs, SciELO, and Cochrane
      library databases. Excluded were articles that specifically analyzed treatment
      modalities and those that did not make their abstracts available in those
      databases. The keywords included were teacher, dysphonia, voice disorders,
      professional voice.

PMID- 24929937
TI  - Overexpression of AtSTO1 leads to improved salt tolerance in Populus tremula * P.
      alba.
AB  - One of the major abiotic stress conditions limiting healthy growth of trees is
      salinity stress. The use of gene manipulation for increased tolerance to abiotic
      stress has been successful in many plant species. Overexpression of the
      Arabidopsis SALT TOLERANT1 (STO1) gene leads to increased concentrations of 9-cis
      epoxycarotenoid dioxygenase3, a vital enzyme in Arabidopsis abscisic acid
      biosynthesis. In the present work, the Arabidopsis STO1 gene (AtSTO1) was
      overexpressed in poplar to determine if the transgene would confer enhanced salt
      tolerance to the generated transgenics. The results of multiple greenhouse trials
      indicated that the transgenic poplar lines had greater levels of resistance to
      NaCl than wild-type plants. Analysis using RT-PCR indicated a variation in the
      relative abundance of the STO1 transcript in the transgenics that coincided with
      tolerance to salt. Several physiological and morphological changes such as
      greater overall biomass, greater root biomass, improved photosynthesis, and
      greater pith size were observed in the transgenics when compared to controls
      undergoing salt stress. These results indicated overexpression of AtSTO1 improved
      salt tolerance in poplar. 

PMID- 24929936
TI  - Is more intensive better? Client and service provider outcomes for intensive
      versus standard therapy schedules for functional voice disorders.
AB  - BACKGROUND: Functional dysphonias are commonly associated with reduced treatment
      attendance leading to variable treatment outcomes. Preliminary research has
      proposed that intensive treatment may improve client adherence and outcomes;
      however, further research into the application of intensive models in functional
      dysphonia in comparison with standard intensity models is warranted. AIMS: The
      present study evaluated the impact of intensive and standard treatments on
      functional, well-being, and service outcome measures in clients with functional
      dysphonia. METHODS: Participants with a functional dysphonia were randomly
      allocated to one of two treatment groups: (1) intensive treatment (n = 7) or (2)
      standard treatment (n = 9). Participants completed the voice handicap index (VHI)
      and the Australian therapy outcome measures voice assessment (conducted by a
      blinded assessor) before and after treatment and 4 weeks after treatment.
      Satisfaction questionnaires were completed after treatment and data pertaining to
      attendance and duration of intervention were collected throughout treatment. In
      addition to a vocal hygiene education session, all participants received a total
      of 8 hours of treatment; intensive treatment consisted of four 1-hour treatment
      sessions per week over 2 weeks, whereas the standard group received one 1-hour
      treatment session per week over 8 weeks. RESULTS: High satisfaction and
      statistically significant improvements on the VHI ratings were found after
      treatment in the intensive group. Significantly greater attendance rates were
      found in the intensive group. Intensive treatment is a potentially viable service
      delivery option for functional dysphonia and warrants further larger scale
      investigation.

PMID- 24929938
TI  - Is what goes in what comes out? Encoding and retrieval event-related potentials
      together determine memory outcome.
AB  - Understanding memory function amounts to identifying how events (cognitive and
      neural) at study eventually influence events at test. Many of the proposed
      cognitive correlates of memory-related event-related potentials (ERPs) at study
      resemble proposed cognitive correlates of other memory-related ERPs, recorded at
      test. We wondered whether a given known ERP feature at study might in fact
      reflect an effective-encoding process that is, in turn, tapped by another
      specific ERP feature, recorded at test. To this end, we asked which pairs of
      known memory-related ERP features explain common variance across a large sample
      of participants, while they perform a word-recognition task. Two early ERP
      features, the Late Positive Component (study) and the FN400 (test), covaried
      significantly. These features also correlated with memory success (d' and
      response time). Two later ERP features, the Slow Wave (study) and the Late
      Parietal Positivity (test), also covaried when lures were incorporated into the
      analysis. Interestingly, these later features were uncorrelated with memory
      outcome. This novel approach, exploiting naturally occurring subject variability
      (in strategy and ERP amplitudes), informs our understanding of the memory
      functions of ERP features in several ways. Specifically, they strengthen the
      argument that the earlier ERP features may drive old/new recognition (but perhaps
      not the later features). Our findings suggest the Late Positive Component at
      study, in some degree, may cause the FN400 to increase at test, together
      producing effective recognition memory. The Slow Wave at study appears to relate
      the Left Parietal Positivity at test, but these may play roles in more complex
      memory judgments and may be less critical for simple old/new recognition.

PMID- 24929939
TI  - Left atrial volume as an independent predictor of exercise capacity in patients
      with isolated diastolic dysfunction presented with exertional dyspnea.
AB  - BACKGROUND: Left atrial volume (LAV) and exercise capacity are important
      prognostic determinants of cardiovascular risk. Exercise intolerance and
      increased LAV are expected in patients with diastolic dysfunction. While dyspnea
      is the symptom reported by the patient and considered subjective, exercise
      capacity obtained by exercise testing provides an objective measure of
      cardiovascular fitness. The objective of this study is to determine the
      relationship between LAV index and exercise capacity in patients with isolated
      diastolic dysfunction who presented with exertional dyspnea. METHODS: We studied
      consecutive patients with dyspnea who underwent treadmill exercise testing and
      transthoracic echocardiography on the same day. LAV was assessed using the
      biplane area-length method. Symptom-limited exercise testing was performed
      immediately after echocardiography. Patients with coronary artery disease,
      valvular or congenital heart disease, left ventricular systolic dysfunction,
      pulmonary hypertension or positive exercise test were excluded. RESULTS: The
      study consisted of 111 patients (58.1 +/- 9.2 years of age, 54.1% male, 64%
      hypertension, 57.7% dyslipidemia and 20.7% diabetes). The exercise duration and
      capacity were 6.8 +/- 2.1 minutes and 7.7 +/- 1.9 METs, respectively. Left
      ventricular ejection fraction and LAV index was 71.0 +/- 5.8% and 31.4 +/- 10.5
      ml/m2, respectively. In multivariate analysis, age [odds ratios (OR) 0.94; 95%
      confidence interval (CI) 0.89-0.99], body mass index (OR 0.82, 95% CI 0.72-0.93),
      and LAV index (OR 0.92, 95% CI 0.87-0.97) were associated with good exercise
      capacity. CONCLUSION: In patients with isolated diastolic dysfunction and
      exertional dyspnea, an increased LAV index, a marker of chronic diastolic
      dysfunction, is associated with poor exercise capacity.

PMID- 24929940
TI  - Data verification at health centers and district health offices in Xiengkhouang
      and Houaphanh Provinces, Lao PDR.
AB  - BACKGROUND: Routine health information is an essential health system building
      block. In low and low-middle income countries however, concerns about the quality
      of routine administrative data have often undermined their use. The purpose of
      the present study was to verify the data availability, and consistency of six key
      maternal and child health indicators (first antenatal care, fourth antenatal
      care, skilled birth attendants, postnatal care, 'Bacillus Calmette Guerin and
      diphtheria-pertussis-tetanus third dose). METHODS: The study collected data for
      the identified indicators in 2011 from Xiengkhouang and Houaphanh provinces in
      the Lao People's Democratic Republic (PDR). The data came from health centres (N
      = 109), sub-districts (N = 26) and district health offices (N = 16). Core
      indicators were calculated using numerators and denominators from the different
      data sources at the district and health centre level and standardized statistical
      tests performed. RESULTS: The study revealed that data for the six indicators
      were either not available or not complete in the service logbooks or registers in
      most of the health centres. Furthermore, few health centres kept the data for up
      to five years, often destroying it once the report had been sent to the district
      health office. In addition, there was limited numerator consistency between the
      different data sources. CONCLUSION: Data on the six indicators collected and
      reported in the public health system across the two provinces lacked
      completeness, accuracy and consistency. To improve the quality of data, there is
      a need to train health centre staff in data collection and recording as well as
      ensuring there is adequate monitoring and supervision. A uniform national
      standardized form is also necessary with findings shared with district health
      offices and centres. Additionally, staff should be encouraged to own and value
      local data.

PMID- 24929942
TI  - Comparison of the metabolic profile of mixed calcium oxalate/uric acid stone
      formers to that of pure calcium oxalate and pure uric acid stone formers.
AB  - OBJECTIVE: To compare the metabolic profile of patients who form mixed calcium
      oxalate (CaOx)/uric acid (UA) stones to those of pure CaOx and pure UA stone
      formers. METHODS: We performed a retrospective review of 232 patients, with both
      stone composition analysis and 24-hour urine collection, seen between March 2002
      and April 2012. Analysis of 24-hour urine constituents across the 3 stone groups
      (pure UA, pure CaOx, and mixed CaOx/UA) was performed using univariate analysis
      of variance and multivariate linear regression models adjusting for clinical and
      demographic factors and 24-hour urine collection elements. RESULTS: A total of 27
      patients (11.6%) had mixed CaOx/UA, 122 (52.6%) had pure CaOx, and 83 (35.8%) had
      pure UA calculi. Univariate analysis demonstrated significant differences between
      mixed CaOx/UA patients and pure CaOx patients for urine pH (mixed, 5.63 +/- 0.49
      vs pure, CaOx 5.93 +/- 0.51; P = .009) and supersaturation (SS) UA (mixed, 1.84
      +/- 1.09 vs pure, CaOx 1.26 +/- 0.93; P = .01), and a significant difference
      between mixed CaOx/UA patients and pure UA patients for SS CaOx (mixed, 7.18 +/-
      4.23 vs pure, UA 4.90 +/- 2.96; P = .005). Multivariate analysis demonstrated
      that mixed CaOx/UA patients had no significant difference in SS CaOx as compared
      with pure CaOx patients (difference, -0.27; P = .66), whereas at the same time
      had no significant difference in SS UA as compared with pure UA patients (-0.07;
      P = .69). CONCLUSION: The metabolic profile of patients who form mixed CaOx/UA
      stones demonstrates abnormalities that promote both CaOx and UA stone formation.
      Dietary and medical management for this group of patients should address
      treatment of both defects.

PMID- 24929941
TI  - Foraging leaf-cutting ants learn to reject Vitis vinifera ssp. vinifera plants
      that emit herbivore-induced volatiles.
AB  - Leaf-cutting ants (LCAs) are dominant herbivores of the Neotropics, as well as
      economically important pests. Their foraging ecology and patterns/mechanisms of
      food selection have received considerable attention. Recently, it has been
      documented that LCAs exhibit a delayed rejection of previously accepted food
      plants following treatment with a fungicide that makes the plants unsuitable as
      substrate for their symbiotic fungus. Here, we investigated whether LCAs
      similarly reject plants with induced chemical defenses, by combining analysis of
      volatile emissions with dual-choice bioassays that used LCA subcolonies (Atta
      sexdens L.). On seven consecutive days, foraging ants were given the choice
      between leaf disks from untreated control plants and test plants of Vitis
      vinifera ssp. vinifera L. treated with the phytohormone jasmonic acid (JA) to
      mimic herbivore attack. Chemical analysis revealed the emission of a
      characteristic set of herbivore-induced volatile organic compounds (VOC) from JA
      induced plants. Dual-choice experiments indicated that workers did not show any
      preference initially, but that they avoided JA-treated plants from day five
      onwards. Our finding that A. sexdens foragers learn to avoid VOC-emitting plants,
      which are likely detrimental to their symbiotic fungus, represents the first
      evidence for avoidance learning in attine ants toward plants with induced
      defenses. 

PMID- 24929943
TI  - Developments in the technique of endoscopic combined intrarenal surgery in the
      prone split-leg position.
AB  - OBJECTIVE: To develop a new technique for performing endoscopic combined
      intrarenal surgery in the prone split-leg position and to evaluate its efficacy
      using computed tomography. MATERIALS AND METHODS: Between December 2010 and
      January 2013, 60 patients with large calculi (39.2 +/- 2.6 mm) underwent this
      surgery. A laser fiber was used with a flexible ureteroscope introduced through a
      ureteral access sheath, and lithoclast lithotripsy was performed through a mini
      percutaneous tract. Three-dimensional computed tomography was performed to
      determine anatomic variations, including the ureteral location and ureteropelvic
      junction angle in all patients in both the supine and prone positions. RESULTS:
      All procedures were performed successfully with a single tract and the patient in
      the prone split-leg position. The mean surgical time was 120.5 +/- 6.7 min. The
      initial stone-free rate was 82%, and the final stone-free rate was 87% after
      further treatment. One patient required blood transfusion, but none had severe
      complications. Computed tomography showed that the ureter between the orifice and
      ureteropelvic junction was straighter and the ureteropelvic junction angle was
      significantly smaller for surgeries conducted in the prone position than the
      supine position. CONCLUSION: Flexible ureteroscopy in the prone split-leg
      position is a viable technique. It allows easy insertion of the ureteral sheath
      and access of the ureteroscope to the renal pelvis. The findings suggest that
      this hybrid surgery is an efficient, effective, and versatile procedure for the
      management of renal calculi.

PMID- 24929944
TI  - Multiple repeat prostate biopsies and the detection of clinically insignificant
      cancer in men with large prostates.
AB  - OBJECTIVE: To determine the impact of repeating prostate biopsies on the risk of
      detecting clinically insignificant prostate cancer (PCa) in larger prostate
      glands. METHODS: We performed a retrospective cohort study using patients
      enrolled in our institutional PCa registry from 1991 to 2008 to assess the
      association of prostate volume and clinically insignificant PCa in men undergoing
      multiple prostate biopsies. Patients were stratified by prostate volume into 2
      cohorts (<50 cm(3) or >=50 cm(3)). Additionally, patients were stratified by
      prostate biopsy on which PCa was identified (1 biopsy or >=3 biopsies). RESULTS:
      Within the subgroup of patients with prostate volume >=50 cm(3) requiring >=3
      biopsies before cancer diagnosis, 72.6% (45/62) had pathologic Gleason scores <=6
      and 81.6% (49/60) had an estimated tumor volume of <=10% at the time of radical
      prostatectomy. This was significantly different from patients with prostate
      volume <50 cm(3) diagnosed on their first biopsy, in which only 48.5% (656/1349)
      were found to have Gleason scores <=6 and 54.2% (705/1300) had estimated tumor
      volume <=10% (P <.01). There was no significant difference in the rate of Gleason
      score upgrading at time of prostatectomy between any of the subgroups.
      CONCLUSION: PCas detected in men with prostatic enlargement requiring multiple
      biopsies are more likely to be low-grade, low-volume tumors at final pathology
      than men without prostate enlargement. Men with larger prostates who have already
      had prior negative biopsies should be counseled regarding the increased risk of
      detecting clinically insignificant PCa with additional biopsies.

PMID- 24929945
TI  - Patient opinions on prostate cancer screening are swayed by the United States
      Preventative Services Task Force recommendations.
AB  - OBJECTIVE: To survey patient opinions on prostate cancer (PCa) screening in light
      of the United States Preventive Services Task Force recommendation against its
      use. METHODS: We conducted a survey of all-comers to urology and primary care
      clinics. Participants provided demographic information and responded to a 5-item
      questionnaire regarding their opinions on screening before and after reading
      opposing position statements. RESULTS: The overall response rate was 48%. After
      excluding incomplete questionnaires, 54 surveys were available for analysis.
      Patients were predominantly white, middle-aged and older, college-educated men
      with middle-to-upper-middle-class incomes who were seen at urology clinics.
      Patients rated their "pre" level of understanding of screening recommendations as
      good or very good (52%), okay (30%), and poor (19%). After reading the
      information sheets, good or very good understanding of screening recommendations
      improved (65%; P = .05), and agreement with the importance of screening remained
      high (80%). However, nearly 20% of patients expressed a more neutral or less
      favorable attitude toward the risk-benefit ratio of screening (P = .09).
      Agreement that men should undergo screening, that screening helps detect cancer,
      and that screening saves lives remained high, regardless of the exposure.
      CONCLUSION: Overall, patients favor PCa screening, but heightened awareness of
      the current controversy raises concerns about its potential harms. PCa screening
      is a complex issue, and insight into changing public opinion will be crucial to
      our future discussions with patients who are wrestling with the decision whether
      to undergo screening.

PMID- 24929946
TI  - Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in
      patients with radiation-induced cystitis: a novel approach.
AB  - INTRODUCTION: This study aimed evaluate the safety and feasibility of endoscopic
      potassium titanyl phosphate (KTP) laser application in the management of patients
      with radiation-induced hemorrhagic cystitis (RHC). TECHNICAL CONSIDERATIONS: We
      retrospectively reviewed the records of 20 patients with RHC who underwent
      endoscopic KTP laser ablation of telangiectatic bladder vessels between October
      2005 and January 2013. After initial cystoscopy, KTP laser was used to ablate the
      submucosal vasculature while preserving the overlying mucosa. The surgical
      outcome was evaluated by duration of hematuria-free interval, number of episodes
      of hematuria, and number of required medical and/or surgical interventions after
      initial treatment. Overall, 20 patients underwent 26 sessions of KTP laser
      ablation of bladder vessels. The procedure was able to stop bleeding 92% of the
      time and the average hematuria-free interval after ablation was 11.8 months, with
      a range of 1-37 months. In 13 patients (65%) hematuria resolved after 1 session
      of KTP laser treatment, whereas 5 patients (25%) required multiple sessions. Two
      patients (10%) with severe hematuria continued to have bleeding after laser
      treatment, which necessitated proximal diversion of urine with percutaneous
      nephrostomy tubes to control bleeding. CONCLUSION: This study suggests that KTP
      laser, with its unique photoselectivity property, is a safe, effective, and
      durable treatment with minimal side effects for ablation of submucosal bladder
      vessels in patients with RHC.

PMID- 24929947
TI  - Robot-assisted partial nephrectomy for >= 7 cm renal masses: a comparative
      outcome analysis.
AB  - OBJECTIVE: To present our robotic partial nephrectomy (RPN) experience for renal
      masses >= 7 cm and compare the surgical outcomes in this cohort with those
      obtained for small (<= 4 cm) renal masses. MATERIALS AND METHODS: We
      retrospectively reviewed our institutional review board-approved RPN database and
      identified patients undergoing RPN for tumors >= 7 cm. Surgical technique, renal
      function, oncologic, and pathologic data were analyzed and compared with the RPN
      for renal masses <= 4 cm. RESULTS: Overall, 441 patients were identified for the
      purpose of this study, including 29 cases and 412 controls. Median operative time
      (200 vs 180 min; P = .005), warm ischemia time (26.5 vs 19 min; P <.001), and
      estimated blood loss (250 mL [353] vs 150 mL [150]; P <.001) were significantly
      lower in the control group. Postoperative complications were significantly higher
      in the case group (37.9% vs 15.8%; P = .005). However, the percentages of major
      complications (Clavien grade >= III) were comparable (18.2% vs 17%; P = .57 for
      cases and controls respectively). Postoperative blood transfusion was higher for
      larger tumor group (24.1% vs 4.1%; P <.001). Positive margins were similar
      between groups (5.9% vs 3.3%; P = .45 for cases and controls respectively). There
      was no difference in estimated glomerular filtration rate decline between the two
      groups (12.2% vs 15.8% decline; P = .98). CONCLUSION: RPN represents a feasible
      and safe nephron-sparing surgery approach for highly selected (mostly exophytic
      growth pattern, polar location, and likelihood of benign histology) renal masses
      >= 7 cm in diameter.

PMID- 24929948
TI  - Prostatic artery embolization for prostate volume greater than 80 cm3: results
      from a single-center prospective study.
AB  - OBJECTIVE: To investigate clinical benefits and safety of prostatic artery
      embolization (PAE) in patients with prostate volume >=80 cm(3) and Charlson
      comorbidity index (CCI) >=2 and affected by benign prostatic obstruction (BPO).
      PATIENTS AND METHODS: From January 2009 to January 2012, PAE was performed in 88
      consecutive patients affected by clinical BPO. Inclusion criteria were
      symptomatic BPO refractory to medical treatment, International Prostate Symptom
      Score (IPSS) >=12, total prostate volume (TPV) >=80 cm(3), Qmax <15 mL/s, and CCI
      >=2. Primary end points were the reduction of 7 points of the IPSS and the
      increase of Qmax. Secondary end points were the reduction of TPV, postvoid
      residue (PVR), prostate-specific antigen (PSA), International Index of Erectile
      Function 5 score, and IPSS-quality of life (QoL). Follow-up was addressed at 3
      months, 6 months, and at 1 year. RESULTS: The mean IPSS (10.40 vs 23.98; P <.05)
      and the mean Qmax (16.89 vs 7.28; P <.05) at 1 year were significantly different
      with respect to baseline. When considering secondary end points, we observed
      significant variation in terms of PVR (18.38 vs 75.25; P <.05), TPV (71.20 vs
      129.31; P <.05), and PSA level (2.12 vs 3.67; P <.05) at 1 year compared with
      baseline. Finally, the mean IPSS-QoL significantly changed from baseline to 1
      year after PAE (5.10 vs 2.20; P <.05). No minor or major complications were
      reported. CONCLUSION: We showed clinical benefits of PAE for the treatment of
      lower urinary tract symptoms and/or BPO by reducing IPSS, TPV, PSA, PVR, and
      improvement in urinary flow and QoL after 1 year in patients with prostate volume
      >=80 cm(3) and CCI >=2.

PMID- 24929949
TI  - Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose
      olanzapine in healthy volunteers.
AB  - Psychosis and other mental illnesses are common in HIV-infected patients.
      Olanzapine is one of the preferred antipsychotic agents for the treatment of
      schizophrenia. Olanzapine is primarily metabolised by CYP1A2 and uridine
      diphosphate glucuronosyltransferase (UGT). High-dose ritonavir has been shown to
      increase olanzapine elimination through induction of CYP1A2 and/or UGT, but the
      effect of low-dose ritonavir on olanzapine pharmacokinetics is unknown.
      Fosamprenavir is an HIV protease inhibitor that is boosted by low-dose ritonavir.
      To compensate for the induction of olanzapine metabolism by
      fosamprenavir/ritonavir, we hypothesised that a dose increase of olanzapine to 15
      mg with fosamprenavir/ritonavir would lead to a similar area under the
      concentration-time curve (AUC) compared with olanzapine 10 mg alone. An open
      label, randomised, two-period, cross-over, single-centre trial was conducted in
      24 healthy volunteers. Subjects were randomised to one of the following
      treatments: (A) fosamprenavir/ritonavir 700/100 mg twice daily (b.i.d.) for 16
      days with a single dose of olanzapine 15 mg on Day 13, a wash-out period of 31
      days and a single dose of olanzapine 10 mg on Day 48; or (B) the same medication
      in reverse order. Twenty subjects completed the trial. The geometric mean ratios
      (90% CI) of olanzapine AUClast, maximum drug concentration (C(max)) and apparent
      elimination half-life (t(1/2)) when taken with fosamprenavir/ritonavir versus
      olanzapine alone were 1.00 (0.93-1.08), 1.32 (1.18-1.47) and 0.68 (0.63-0.74),
      respectively. Fosamprenavir/ritonavir 700/100 mg b.i.d. appeared to induce
      olanzapine metabolism. We therefore propose a 50% dosage increase of olanzapine
      when combining with a ritonavir-boosted protease inhibitor.

PMID- 24929950
TI  - PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin.
AB  - The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing
      angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K
      PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1),
      which is known to contextually promote tumor angiogenesis and growth. Loss of PAI
      1 abrogated the antitumoral and antiangiogenic effects of 16K PRL. PAI-1 bound
      the ternary complex PAI-1-urokinase-type plasminogen activator (uPA)-uPA receptor
      (uPAR), thereby exerting antiangiogenic effects. By inhibiting the
      antifibrinolytic activity of PAI-1, 16K PRL also protected mice against
      thromboembolism and promoted arterial clot lysis. Thus, by signaling through the
      PAI-1-uPA-uPAR complex, 16K PRL impairs tumor vascularization and growth and, by
      inhibiting the antifibrinolytic activity of PAI-1, promotes thrombolysis. 

PMID- 24929952
TI  - Yes! Sex matters: sex, the brain and blood pressure.
AB  - The role of the brain in hypertension between the sexes is known to be important
      especially with regards to the effects of circulating sex hormones. A number of
      different brain regions important for regulation of sympathetic outflow and blood
      pressure express estrogen receptors (ERalpha and ERbeta). Estradiol, acting
      predominantly via the ERalpha, inhibits angiotensin II activation of the area
      postrema and subfornical organ neurons and inhibits reactive oxygen generation
      that is required for the development of Angiotensin II-induced neurogenic
      hypertension. Estradiol activation of ERbeta within the paraventricular nucleus
      and the rostral ventral lateral medulla inhibits these neurons and inhibits
      angiotensin II, or aldosterone induced increases in sympathetic outflow and
      hypertension. Understanding the cellular and molecular mechanisms underlying
      ERalpha and ERbeta actions within key brain regions regulating blood pressure
      will be essential for the development of "next generation" selective estrogen
      receptor modulators (SERMS) that can be used clinically for the treatment of
      neurogenic hypertension. 

PMID- 24929951
TI  - Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal
      axis.
AB  - Leptin treatment reverses hyperglycemia in animal models of poorly controlled
      type 1 diabetes (T1D), spurring great interest in the possibility of treating
      patients with this hormone. The antidiabetic effect of leptin has been postulated
      to occur through suppression of glucagon production, suppression of glucagon
      responsiveness or both; however, there does not appear to be a direct effect of
      leptin on the pancreatic alpha cell. Thus, the mechanisms responsible for the
      antidiabetic effect of leptin remain poorly understood. We quantified liver
      specific rates of hepatic gluconeogenesis and substrate oxidation in conjunction
      with rates of whole-body acetate, glycerol and fatty acid turnover in three rat
      models of poorly controlled diabetes, including a model of diabetic ketoacidosis.
      We show that the higher rates of hepatic gluconeogenesis in all these models
      could be attributed to hypoleptinemia-induced activity of the hypothalamic
      pituitary-adrenal (HPA) axis, resulting in higher rates of adipocyte lipolysis,
      hepatic conversion of glycerol to glucose through a substrate push mechanism and
      conversion of pyruvate to glucose through greater hepatic acetyl-CoA allosteric
      activation of pyruvate carboxylase flux. Notably, these effects could be
      dissociated from changes in plasma insulin and glucagon concentrations and
      hepatic gluconeogenic protein expression. All the altered systemic and hepatic
      metabolic fluxes could be mimicked by infusing rats with Intralipid or
      corticosterone and were corrected by leptin replacement. These data demonstrate a
      critical role for lipolysis and substrate delivery to the liver, secondary to
      hypoleptinemia and HPA axis activity, in promoting higher hepatic gluconeogenesis
      and hyperglycemia in poorly controlled diabetes. 

PMID- 24929954
TI  - Investigation of paternity with alleged father deceased or missing: analysis of
      success at the end of the report.
AB  - In this work we present a retrospective study of 858 cases of paternity
      investigation performed in Rio Grande do Sul, Southern Brazil, from 2007 to 2012,
      where the alleged father was deceased or missing. These cases represent 3.3%
      (858/26187) of paternity tests performed in that period. Considering the analysis
      of 17 DNA short tandem repeat loci, we present here the proportion of cases with
      conclusive results according to the number of relatives of the unavailable
      alleged father investigated and their kinship. The results show 81.0% (695/858)
      of cases with conclusive results and their characteristics. 

PMID- 24929953
TI  - Vitamin D deficiency in the pathogenesis of hypertension: still an unsettled
      question.
AB  - Vitamin D deficiency is inversely associated with blood pressure and is felt to
      contribute to the genesis and maintenance of hypertension. Although well
      demonstrated in animal studies, in many clinical studies the association between
      vitamin D status and blood pressure has not been consistently observed or else
      has been quite small. These discrepancies may relate in part to methodological
      differences including: patient selection, study size and duration, and, in the
      case of vitamin D repletion studies, differences in the vitamin D supplement
      used, its dose, and dosing intervals. Polymorphisms in genes regulating vitamin D
      activation and function may explain some of the observed inconsistencies as
      suggested by recent studies. The present review examines experimental and
      clinical studies bearing on the inverse association between blood pressure and
      vitamin D status and concludes that a new definition of vitamin D deficiency
      using additional biomarkers may better select patients with hypertension who will
      respond to vitamin D supplementation. 

PMID- 24929956
TI  - Sown species richness and realized diversity can influence functioning of plant
      communities differently.
AB  - Biodiversity-ecosystem functioning experiments (BEF) typically manipulate sown
      species richness and composition of experimental communities to study ecosystem
      functioning as a response to changes in diversity. If sown species richness is
      taken as a measure of diversity and aboveground biomass production as a measure
      of community functioning, then this relationship is usually found to be positive.
      The sown species richness can be considered the equivalent of a local species
      pool in natural communities. However, in addition to species richness, realized
      diversity is also an important community diversity component. Realized diversity
      is affected by environmental filtering and biotic interactions operating within a
      community. As both sown species richness and the realized diversity in BEF
      studies (as well as local species pool vs observed realized richness in natural
      communities) can differ markedly, so can their effects on the community
      functioning. We tested this assumption using two data sets: data from a short
      term pot experiment and data from the long-term Jena biodiversity plot
      experiment. We considered three possible predictors of community functioning
      (aboveground biomass production): sown species richness, realized diversity
      (defined as inverse of Simpson dominance index), and survivor species richness.
      Sown species richness affected biomass production positively in all cases.
      Realized diversity as well as survivor species richness had positive effects on
      biomass in approximately half of cases. When realized diversity or survivor
      species richness was tested together with sown species richness, their partial
      effects were none or negative. Our results suggest that we can expect positive
      diversity-productivity relationship when the local species pool size is the
      decisive factor determining realized observed diversity; in other cases, the
      shape of the diversity-functioning relationship may be quite opposite. 

PMID- 24929955
TI  - Serum uric acid predicts vascular complications in adults with type 1 diabetes:
      the coronary artery calcification in type 1 diabetes study.
AB  - Epidemiologic evidence supports a link between serum uric acid (SUA) and vascular
      complications in diabetes, but it remains unclear whether SUA improves the
      ability of conventional risk factor to predict complications. We hypothesized
      that SUA at baseline would independently predict the development of vascular
      complications over 6 years and that the addition of SUA to American Diabetes
      Association's ABC risk factors (HbA1c, BP, LDL-C) would improve vascular
      complication prediction over 6 years in adults with type 1 diabetes. Study
      participants (N = 652) were 19-56 year old at baseline and re-examined 6 years
      later. Diabetic nephropathy was defined as incident albuminuria or rapid GFR
      decline (>3.3 %/year) estimated by the CKD-EPI cystatin C. Diabetic retinopathy
      (DR) was based on self-reported history, and proliferative diabetic retinopathy
      (PDR) was defined as laser eye therapy; coronary artery calcium (CAC) was
      measured using electron-beam computed tomography. Progression of CAC (CACp) was
      defined as a change in the square-root-transformed CAC volume >=2.5. Predictors
      of each complication were examined in stepwise logistic regression with subjects
      with complications at baseline excluded from analyses. C-statistics, integrated
      discrimination indices and net-reclassification improvement were utilized for
      prediction performance analyses. SUA independently predicted development of
      incident albuminuria (OR 1.8, 95 % CI 1.2-2.7), rapid GFR decline (1.9, 1.1-3.3),
      DR (1.4, 1.1-1.9), PDR (2.1, 1.4-3.0) and CACp (1.5, 1.1-1.9). SUA improved the
      discrimination and net-classification risk of vascular complications over 6
      years. SUA independently predicted the development of vascular complications in
      type 1 diabetes and also improved the reclassification of vascular complications.

PMID- 24929957
TI  - Case report: bipolar disorder as the first manifestation of CADASIL.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease,
      clinically characterized by variable manifestations of migraine, recurrent
      transient ischemic attack or lacunar strokes, cognitive decline, and mood
      disturbances. However, manic episodes have rarely been documented as an initial
      symptom of CADASIL and bipolar disorder presenting as the first manifestation in
      CADASIL has not been reported previously from evaluations by psychiatrists or
      psychological testing by psychologists. CASE PRESENTATION: A 53 year old woman
      developed symptoms of mania in her 50s leading to a personality change involving
      a continuously labile mood and irritability over a number of years.
      Neuropsychological testing revealed an intact memory, but impairment in attention
      and executive function. In the Rorschach test, she showed a high level of
      cognitive rigidity. Magnetic resonance imaging findings were very consistent with
      a diagnosis of CADASIL, which was confirmed by genetic testing for NOTCH3
      mutations. Atypical antipsychotics proved to be helpful in treating her manic
      symptoms and for behavior control. CONCLUSION: We present a novel case of CADASIL
      that first presented as bipolar disorder. We contend that when patients show a
      late onset personality change or chronically irritable mood that deteriorates
      over many years, an organic cause such as CADASIL must be considered. Further
      studies are needed to better understand the exact impacts of cerebral tissue
      lesions and psychiatric symptoms in CADASIL patients.

PMID- 24929958
TI  - Dynamic study of the hippocampal volume by structural MRI in a rat model of
      depression.
AB  - The reduction of hippocampal volume remains controversial in depression because
      of the variability among individuals in clinical studies. Here, a reliable
      experimental rat model of depression, established by chronic unpredictable mild
      stress (CUMS), was used. Thirty rats were randomly divided into two groups (CUMS
      group and control group). Hippocampal volume was dynamically measured every 2
      weeks in a 56-day chronic stress procedure using structural magnetic resonance
      imaging, and the correlation between the hippocampal volume and the learning and
      memory changes was investigated. Our results demonstrated that CUMS rats showed
      significantly smaller volumes of the bilateral hippocampus compared to that of
      the controls, changing dramatically with the development of CUMS procedure. The
      left hippocampal volume was reduced earlier and more markedly than the right one
      from the 2nd week to the 8th week of the CUMS procedure (on the 8th week: left:
      approximately 15.3 %; right: approximately 8.4 % reduction). Additionally, the
      hippocampal volume of CUMS rats was significantly negatively correlated with the
      learning and memory changes. Of note, it showed that the more obviously the
      hippocampal volume reduced, the more severely the learning and memory damaged. In
      conclusion, the hippocampal volume decreased gradually and dynamically and was
      correlated with the impairment of the learning and memory in depression.

PMID- 24929959
TI  - Continuous renal replacement therapy (CRRT) for rhabdomyolysis.
AB  - BACKGROUND: Rhabdomyolysis is a condition that is characterised by the breakdown
      of skeletal muscle tissue and leakage of intracellular myocyte contents into
      circulating blood. Rhabdomyolysis can lead to acute kidney injury (AKI) and is a
      potentially life-threatening condition. Studies have indicated that continuous
      renal replacement therapy (CRRT) may provide benefits for people with
      rhabdomyolysis by removing potentially damaging myoglobin and stabilising
      haemodynamic and metabolic status. OBJECTIVES: We aimed to: i) assess the
      efficacy of CRRT in removing myoglobin; ii) investigate the influence of CRRT on
      mortality and kidney-related outcomes; and iii) evaluate the safety of CRRT for
      the treatment of people with rhabdomyolysis. SEARCH METHODS: We searched the
      Cochrane Renal Group's Specialised Register to 6 January 2014 through contact
      with the Trials' Search Co-ordinator using search terms relevant to this review.
      We also searched China National Knowledge Infrastructure (from 1 January 1979 to
      16 April 2013) and the Chinese Clinical Trials Register (to 16 April 2013).
      SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs that
      investigated clinical outcomes of CRRT for people with rhabdomyolysis were
      included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      studies for inclusion and extracted data. We derived risk ratios (RR) for
      dichotomous data and mean differences (MD) for continuous data with 95%
      confidence intervals (CI). Methodological risk of bias was assessed using the
      Cochrane risk of bias tool. MAIN RESULTS: Of the three included studies (101
      participants), one evaluated continuous arteriovenous haemodialysis and two
      investigated continuous venovenous haemofiltration; all included conventional
      therapy as control.We found significant decreases in myoglobin in patients among
      whom CRRT therapy was initiated on days four, eight, and 10 (day 4: MD -11.00
      (MUg/L), 95% CI -20.65 to -1.35; Day 8: MD -23.00 (MUg/L), 95% CI -30.92 to 
      15.08; day 10: MD -341.87 (MUg/L), 95% CI -626.15 to -57.59) compared with those
      who underwent conventional therapy.Although CRRT was associated with improved
      serum creatinine, blood urea nitrogen, and potassium levels; reduced duration of
      the oliguria phase; and was associated with reduced time in hospital, no
      significant differences were found in mortality rates compared with conventional
      therapy (RR 0.17, 95% CI 0.02 to 1.37). The included studies did not report on
      long-term outcomes or prevention of AKI.Overall, we found that study quality was
      suboptimal: blinding and randomisation allocation were not reported by any of the
      included studies, leading to the possibility of selection, performance and
      detection bias. AUTHORS' CONCLUSIONS: Although CRRT may provide some benefits for
      people with rhabdomyolysis, the poor methodological quality of the included
      studies and lack of data relating to clinically important outcomes limited our
      findings about the effectiveness of CRRT for people with rhabdomyolysis.There was
      insufficient evidence to discern any likely benefits of CRRT over conventional
      therapy for people with rhabdomyolysis and prevention of rhabdomyolysis-induced
      AKI.

PMID- 24929960
TI  - Determination of cephalomannine in rat plasma by gradient elution UPLC-MS/MS
      method.
AB  - A rapid, sensitive and selective ultra-performance liquid chromatography tandem
      mass spectrometry (UPLC-MS/MS) was developed and validated for the determination
      and pharmacokinetic investigation of cephalomannine in rat plasma. Sample
      preparation was accomplished through a simple one-step deproteinization procedure
      with 0.2 mL of perchloric acid-methanol (1:9, v/v) to a 0.1 mL plasma sample.
      Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a
      mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient
      elution. The total run time was 2.0 min and the elution of cephalomannine was at
      1.60 min. The detection was performed on a triple quadrupole tandem mass
      spectrometer in the multiple reaction-monitoring (MRM) mode using the respective
      transitions m/z 832.8->264.1 for cephalomannine and m/z 812.6->286.0 for 10-DAT
      (internal standard), respectively. The calibration curve was linear over the
      range of 10-2,000 ng/mL with a lower limit of quantitation (LLOQ) of 10 ng/mL.
      Mean recovery of cephalomannine in plasma was in the range of 80.9-85.3%. Intra
      day and inter-day precision were both <11.2%. This method was successfully
      applied in pharmacokinetic study after intravenous administration of 5.0mg/kg
      cephalomannine in rats.

PMID- 24929961
TI  - Synthesis and preclinical evaluation of carbon-11 labelled N-((5-(4-fluoro-2
      [(11)C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine as a PET tracer for
      NR2B subunit-containing NMDA receptors.
AB  - INTRODUCTION: The N-methyl-D-Aspartate (NMDA) receptor plays an important role in
      learning and memory. Overactivation is thought to play an important role in
      neurodegenerative disorders such as Alzheimer's disease. Currently, it is not
      possible to assess N-methyl-D-aspartate receptor (NMDAr) bio-availability in
      vivo. The purpose of this study was to develop a positron emission tomography
      (PET) ligand for the NR2B binding site of the NMDA receptor. METHODS: N-((5-(4
      fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was radiolabelled
      with carbon-11 in the phenyl moiety. Biodistribution and blocking studies were
      carried out in anaesthetized mice and in non-anaesthetized rats. RESULTS: N-((5
      (4-fluoro-2-[(11)C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was
      prepared in 49+/-3% (decay-corrected) yield, affording 4.1+/-0.3 GBq of
      formulated product at the end of synthesis with a radiochemical purity of >99%
      and with a specific activity of 78+/-10 GBq/MUmol. CONCLUSION: A new NR2B PET
      ligand was developed in high yield. [(11)C]4 readily enters the brain and binds
      to the NR2B subunit-containing NMDAr in the rodent brain. High sigma-1 receptor
      binding may, however, limit its future application as a PET probe for imaging the
      NR2B subunit-containing NMDAr. Anaesthesia has an effect on NMDAr function and
      therefore can complicate interpretation of preclinical in vivo results. In
      addition, effects of endogenous compounds cannot be excluded. Despite these
      potential limitations, further studies are warranted to investigate the values of
      [(11)C]4 as an NR2B PET ligand.

PMID- 24929962
TI  - Photo-production of (99)Mo/(99m)Tc with electron linear accelerator beam.
AB  - We report on the development of a relatively new method for the production of
      (99)Mo/(99m)Tc. The method involves the irradiation of natural molybdenum using
      high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear
      electron accelerator located at the Yerevan Physics Institute (YerPhi). The
      production method has been developed and shown to be successful. The linear
      electron accelerator at YerPhi was upgraded to allow for significant increases of
      the beam intensity and spatial density. The LUE50 was also instrumented by a
      remote control system for ease of operation. We have developed and tested the
      (99m)Tc extraction from the irradiation of natural MoO3. This paper reports on
      the optimal conditions of our method of (99)Mo production. We show the success of
      this method with the production and separation of the first usable amounts of
      (99m)Tc. 

PMID- 24929963
TI  - Prognostic value of 3'-deoxy-3'-18F-fluorothymidine ([(18)F] FLT PET) in patients
      with recurrent malignant gliomas.
AB  - INTRODUCTION: 3'-deoxy-3'-18F-fluorothymidine ([(18)F] FLT) PET has been proven
      to be of value in diagnosis and assessment of glioma grading, in differentiating
      tumor recurrence from necrosis, in response assessment and in predicting overall
      survival (OS) in the primary high grade glioma. In this study, we evaluated the
      value of [(18)F] FLT PET-CT in predicting the OS of patients with recurrent
      malignant glioma. METHODS: Fifty-six patients with recurrent malignant glioma
      were enrolled in this prospective study. The PET-CT and contrast-enhanced MRI
      scans were performed in all patients. Tumor volume was determined from both PET
      image (proliferative volume, PV) and MRI image (Vol-MRI). Patients were followed
      up clinically until death. The likelihood of using PET-derived parameters of
      SUVmax, tumor-to-normal (T/N) ratio, and PV to predict the OS of patients were
      assessed in comparison with Vol-MRI and other clinical parameters. RESULT: The
      follow up periods for all patients ranged from 1.5 to 35.6 months with median of
      9.8 months. Univariate analysis showed that the following parameters were
      significantly correlated with OS: grade of primary tumor (p=0.042), Karnofsky
      performance score (KPS) (p=0.041), T/N ratio (p<0.01), Vol-MRI (p=0.041), and PV
      (p<0.001). However, multivariate Cox regression showed that only the PV (p<0.001)
      and T/N ratio (p=0.001) were independent predictors. The thresholds to predict OS
      were 16.88 cm(3) for PV and 10.94 for T/N ratio. Kaplan-Meier analyses using
      these thresholds showed a significant discrimination between short and long OS
      groups (p<0.001). CONCLUSION: The PV and T/N ratio of tumor on [(18)F] FLT PET-CT
      are independent predictors of survival in patients with recurrent malignant
      glioma. The PV on [(18)F] FLT PET seems to be more predictive than tumor volume
      on T1-weighted MRI for OS.

PMID- 24929964
TI  - The transcription factor Pou3f1 promotes neural fate commitment via activation of
      neural lineage genes and inhibition of external signaling pathways.
AB  - The neural fate commitment of pluripotent stem cells requires the repression of
      extrinsic inhibitory signals and the activation of intrinsic positive
      transcription factors. However, how these two events are integrated to ensure
      appropriate neural conversion remains unclear. In this study, we showed that
      Pou3f1 is essential for the neural differentiation of mouse embryonic stem cells
      (ESCs), specifically during the transition from epiblast stem cells (EpiSCs) to
      neural progenitor cells (NPCs). Chimeric analysis showed that Pou3f1 knockdown
      leads to a markedly decreased incorporation of ESCs in the neuroectoderm. By
      contrast, Pou3f1-overexpressing ESC derivatives preferentially contribute to the
      neuroectoderm. Genome-wide ChIP-seq and RNA-seq analyses indicated that Pou3f1 is
      an upstream activator of neural lineage genes, and also is a repressor of BMP and
      Wnt signaling. Our results established that Pou3f1 promotes the neural fate
      commitment of pluripotent stem cells through a dual role, activating internal
      neural induction programs and antagonizing extrinsic neural inhibitory signals. 

PMID- 24929965
TI  - Optimal multisensory decision-making in a reaction-time task.
AB  - Humans and animals can integrate sensory evidence from various sources to make
      decisions in a statistically near-optimal manner, provided that the stimulus
      presentation time is fixed across trials. Little is known about whether
      optimality is preserved when subjects can choose when to make a decision
      (reaction-time task), nor when sensory inputs have time-varying reliability.
      Using a reaction-time version of a visual/vestibular heading discrimination task,
      we show that behavior is clearly sub-optimal when quantified with traditional
      optimality metrics that ignore reaction times. We created a computational model
      that accumulates evidence optimally across both cues and time, and trades off
      accuracy with decision speed. This model quantitatively explains subjects's
      choices and reaction times, supporting the hypothesis that subjects do, in fact,
      accumulate evidence optimally over time and across sensory modalities, even when
      the reaction time is under the subject's control. 

PMID- 24929966
TI  - Plant phytochemicals: potential anticancer agents against gastric cancer.
AB  - Isothiocyanates (ITCs) are plant phytochemicals derived from vegetables consumed
      by human. ITCs comprise potent anti-carcinogenic agents of which the consumption
      has been linked to a reduced risk of cancer at several locations in the body.
      However, the studies on coping with gastric cancer remain unsatisfied. In the
      present review, ITCs are discussed in this context as ITCs may target gastric
      tumorigenesis at multiple levels. ITCs are taken up in the stomach, exposing
      mucosal and muscle layer cells as well as affecting Helicobacter pylori residing
      in the stomach. The natural and potent anti-cancer ITCs from vegetables have a
      great potential against gastric cancer, a disease in need of new treatment or
      preventive modalities. 

PMID- 24929967
TI  - NSAID-gastroenteropathy: new aspects of pathogenesis and prevention.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) remain among the most commonly used
      medications because of their effectiveness in reducing pain and inflammation.
      Inhibitors of gastric acid secretion can substantially reduce the damaging
      effects of NSAIDs in the stomach and duodenum. However, there are no proven
      effective preventative or curative treatments for NSAID-induced enteropathy. In
      recent years, substantial progress has been made in better understanding the
      pathogenesis of NSAID-enteropathy, and in particular the interplay of enteric
      bacteria, bile and the enterohepatic recirculation of the NSAIDs. Moreover, it is
      becoming clear that suppression of gastric acid secretion significantly worsens
      NSAID-enteropathy. 

PMID- 24929968
TI  - Iron and multiple sclerosis.
AB  - Iron is essential for normal cellular functioning of the central nervous system.
      Abnormalities in iron metabolism may lead to neuronal death and abnormal iron
      deposition in the brain. Several studies have suggested a link between brain iron
      deposition in normal aging and chronic neurologic diseases, including multiple
      sclerosis (MS). In MS, it is still not clear whether iron deposition is an
      epiphenomenon or a mediator of disease processes. In this review, the role of
      iron in the pathophysiology of MS will be summarized. In addition, the importance
      of conventional and advanced magnetic resonance imaging techniques in the
      characterization of brain iron deposition in MS will be reviewed. Although there
      is currently not enough evidence to support clinical use of iron chelation in MS,
      an overview of studies of iron chelation or antioxidant therapies will be also
      provided. 

PMID- 24929970
TI  - Death by color: differential cone loss in the aging mouse retina.
AB  - Differential cell death is a common feature of aging and age-related disease. In
      the retina, 30% of rod photoreceptors are lost over life in humans and rodents.
      However, studies have failed to show age-related cell death in mouse cone
      photoreceptors, which is surprising because cone physiological function declines
      with age. Moreover in human, differential loss of short wavelength cone function
      is an aspect of age-related retinal disease. Here, cones are examined in young (3
      month-old) and aged (12-month-old) C57 mice and also in complement factor H knock
      out mice (CFH-/-) that have been proposed as a murine model of age-related
      macular degeneration. In vivo imaging showed significant age-related reductions
      in outer retinal thickness in both groups over this period. Immunostaining for
      opsins revealed a specific significant decline of >20% for the medium/long (M/L)
      wavelength cones but only in the periphery. S cones numbers were not
      significantly affected by age. This differential cell loss was backed up with
      quantitative real-time polymerase chain reaction for the 2 opsins, again showing
      S opsin was unaffected, but that M/L opsin was reduced particularly in CFH-/-
      mice. These results demonstrate aged cone loss, but surprisingly, in both
      genotypes, it is only significant in the peripheral ventral retina and focused on
      the M/L population and not S cones. We speculate that there may be fundamental
      differences in differential cone loss between human and mouse that may question
      the validity of mouse models of human outer retinal aging and pathology.

PMID- 24929971
TI  - Effects of cedar pollen extract on the immune system in vitro.

PMID- 24929969
TI  - APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults
      older than 50 years.
AB  - Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimer's
      disease (AD). APOE epsilon4, the major genetic risk factor for late-onset AD, has
      been associated with smaller volume in these regions before amyloidosis can be
      detected by AD biomarkers. To examine APOE epsilon4 effects in relation to aging,
      we performed a longitudinal magnetic resonance imaging study involving
      cognitively normal adults (25 APOE epsilon4 carriers and 31 epsilon3
      homozygotes), initially aged 51-75 years. We used growth curve analyses, which
      can provide information about APOE epsilon4-related differences initially and
      later in life. Hippocampal volume was the primary outcome; nearby medial temporal
      regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was
      a secondary covariate. APOE epsilon4 carriers had significantly smaller initial
      hippocampal volumes than epsilon3 homozygotes. Rate of hippocampal atrophy was
      not greater in the APOE epsilon4 group, although age-related atrophy was detected
      in the overall sample. The findings add to the growing evidence that effects of
      APOE epsilon4 on hippocampal size begin early in life, underscoring the
      importance of early interventions to increase reserve.

PMID- 24929972
TI  - X-linked hyper IgM syndrome: clinical, immunological and molecular features in
      patients from India.
AB  - BACKGROUND: X-linked hyper-IgM (XHIM) is a primary immunodeficiency disorder
      characterized by recurrent infections, low serum IgG and IgA and normal or
      elevated IgM. It results from mutations in the CD40 ligand (CD40L) gene.
      Confirmation of diagnosis with identification of underlying molecular defect is
      important for the initiation of appropriate therapeutic interventions, including
      immunoglobulin replacement, antibiotics and bone marrow transplantation. METHODS:
      To investigate the molecular basis of XHIM, we evaluated 7 patients with
      suspected XHIM and abnormal CD40L expression on activated CD4(+) T lymphocytes.
      The entire coding region and intronic splice sites of the CD40L gene were
      sequenced from the genomic DNA of the patients. RESULTS: 7 mutations; 3 nonsense
      (c.172delA, c.A229T, c.C478T), 1 missense (c.A506G) and 3 splice sites [c.346+2(T
      >C), c.289-1(G->C), c.346+1(G->T)] were identified, out of which 5 were novel.
      CONCLUSION: A wide heterogeneity in the nature of mutations has been observed in
      Indian XHIM patients in the present study. Identification of mutations in this
      rare disorder will help in genetic diagnosis in affected families which could be
      further useful in prenatal diagnosis.

PMID- 24929973
TI  - [Practices and interventions related to the work integration of people with a
      severe mental illness: work outcomes and avenues of research].
AB  - Sustained work integration for people with a severe mental illness or handicap
      psychique in French (e.g., schizophrenia) is an important issue in our society
      today. Indeed, work is not only an essential factor in people's social
      integration but is also a stepping-stone toward recovery for this clientele. Well
      defined programs and services related to work integration were developed and
      studied over the last three decades. Although the work integration of people with
      severe mental illness has been studied extensively in the Anglo-Saxon literature,
      the impact of these studies on the traditional beliefs and services in France
      remains uncertain. In terms of the scope of the studies so far, there has been an
      initial interest lasting over many years to uncover individual characteristics of
      people with severe mental illness which would best predict job tenure. Since,
      studies have been increasingly investigating various supports in order to
      facilitate the work integration process. These supports can be illustrated as
      direct supports or accommodations offered in the workplace, as needed,
      particularly when people with severe mental illness choose to disclose their
      mental disorder in the workplace. This awareness of the impact of the workplace
      environment on the work integration of people with a severe mental illness
      increases the need to find solutions and develop environmentally sensitive
      clinical strategies to overcome difficulties during the work integration. To
      illustrate this thematic, in this special issue, we have gathered together
      studies conducted in different countries but who share the focus on work
      integration of people with a severe mental illness. To reflect the advancement in
      this domain, this special issue is divided in three parts. The first part
      consists of the presentation of different types of vocational programs: supported
      employment programs, social firms, and hybrid models. Supported employment
      programs are very well documented in the specialised literature and are
      recognized as an evidence-based practice across the world to help people get
      competitive employment. Social firms is an another alternative model for
      facilitating the work integration of people with severe mental illness but has to
      date scarcely been studied empirically. Other hybrid vocational programs
      implemented in Quebec (Canada) and France and inspired by supported employment
      programs and social firms' principles, are also described. The second part of
      this special issue is related to the presentation of two adjunct clinical
      interventions for helping people with a severe mental illness in their work
      integration, and more particularly for increasing job tenure: cognitive
      remediation and group cognitive behavioral therapy. Cognitive remediation was
      developed to reduce the impact of cognitive deficits, such as memory or
      attention, in people with a severe mental illness whereas group cognitive
      behavioral therapy was developed to change the dysfunctional beliefs and
      behaviours that might hinder job tenure in people receiving supported employment
      services. Finally, the third part of this special issue presents two papers on
      the influence of the workplace, of stakeholders from the organization (e.g.,
      employers, supervisors) and of the work environment on the work integration of
      people with severe mental illness. The first paper discusses disclosure of the
      mental illness in the workplace and its positive and negative consequences such
      as receiving work accommodations and experiencing stigma, respectively. In the
      last paper, psychological processes during the hiring process are presented to
      better understand the elements related to discrimination and stigma during the
      work integration of people with severe mental illness. 

PMID- 24929974
TI  - Supported employment for persons with serious mental illness: current status and
      future directions.
AB  - The individual placement and supported (IPS) model of supported employment is the
      most empirically validated model of vocational rehabilitation for persons with
      schizophrenia or another serious mental illness. Over 18 randomized controlled
      trials have been conducted throughout the world demonstrating the effectiveness
      of supported employment at improving competitive work compared to other
      vocational programs: IPS supported employment is defined by the following
      principles: 1) inclusion of all clients who want to work; 2) integration of
      vocational and clinical services; 3) focus on competitive employment; 4) rapid
      job search and no required prevocational skills training; 5) job development by
      the employment specialist; 6) attention to client preferences about desired work
      and disclosure of mental illness to prospective employers; 7) benefits
      counseling; and 8) follow-along supports after a job is obtained. Supported
      employment has been successfully implemented in a wide range of cultural and
      clinical populations, although challenges to implementation are also encountered.
      Common challenges are related to problems such as the failure to access technical
      assistance, system issues, negative beliefs and attitudes of providers, funding
      restrictions, and poor leadership. These challenges can be overcome by tapping
      expertise in IPS supported employment, including standardized and tested models
      of training and consultation. Efforts are underway to increase the efficiency of
      training methods for supported employment and the overall program, and to improve
      its effectiveness for those clients who do not benefit. Progress in IPS supported
      employment offers people with a serious mental illness realistic hope for
      achieving their work goals, and taking greater control over their lives. 

PMID- 24929975
TI  - Tocotrienols in Vellozia gigantea leaves: occurrence and modulation by seasonal
      and plant size effects.
AB  - Vitamin E occurs in all photosynthetic organisms examined to date. Tocopherols
      predominate in photosynthetic tissues (alpha-tocopherol being the major form),
      while either tocopherols or tocotrienols (or both) are present in seeds.
      Tocotrienols have not been described in photosynthetic tissues thus far. Here, we
      report on the presence of tocotrienols in leaves of higher plants. Both
      tocopherols and tocotrienols accumulated in leaves of Vellozia gigantea, an
      endemic plant found in the rupestrian fields of Serra do Cipo, Brazil. Increased
      plant size had a remarkable effect on the vitamin E composition of leaves, alpha
      tocopherol and beta-tocotrienol levels being highest in the largest individuals,
      but only during the dry season. Vitamin E levels positively correlated with lipid
      hydroxyperoxide levels, which also increased in the largest individuals during
      the dry season. However, the maximum efficiency of PSII photochemistry (F v/F m
      ratio) kept above 0.75 throughout the experiment, thus indicating absence of
      photoinhibitory damage to the photosynthetic apparatus. It is concluded that
      higher plants, such as V. gigantea, can accumulate tocotrienols in leaves, aside
      from tocopherols, and that the levels of both tocopherols and tocotrienols in the
      leaves of this species are strongly modulated by seasonal and plant size effects.

PMID- 24929976
TI  - Backbone modification of a polypeptide drug alters duration of action in vivo.
AB  - Systematic modification of the backbone of bioactive polypeptides through beta
      amino acid residue incorporation could provide a strategy for generating
      molecules with improved drug properties, but such alterations can result in lower
      receptor affinity and potency. Using an agonist of parathyroid hormone receptor-1
      (PTHR1), a G protein-coupled receptor in the B-family, we present an approach for
      alpha->beta residue replacement that enables both high activity and improved
      pharmacokinetic properties in vivo. 

PMID- 24929977
TI  - Size distribution studies of 137Cs in river water in the Abukuma Riverine system
      following the Fukushima Dai-ichi Nuclear Power Plant accident.
AB  - The occurrence of (137)Cs in size fractionated samples in river water from the
      Abukuma River system, (the Kuchibuto and Abukuma Rivers, five sampling events for
      three sites) was studied from June 2011--approximately some three months after
      the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident until December 2012.
      The total concentration of (137)Cs (mBq/L) in river water was generally high at
      the upper stream site in the Yamakiya District within the evacuation/off-limits
      zone. The (137)Cs concentration was about 1Bq/L for the first sampling campaign
      (June 2011) at all sites, but then decreased substantially to about one-tenth of
      that by the time of a second sampling campaign (November or December 2011). The
      (137)Cs in the <0.45 MUm fraction was present exclusively as a dissolved species
      rather than as a species adsorbed on suspended solids or complexed with organic
      materials. The contribution of the dissolved fraction ranged from 1.2 to 48.9%
      (averaged 20%) of the total concentration of (137)Cs throughout the observation
      period. The maximum contribution of (137)Cs was found in the silt size fraction
      (3-63 MUm), which can be explained by the relatively large Kd values and the
      suspended solids (SS) concentration of this size fraction. Although the
      concentration (Bq/g) of (137)Cs in each size fraction did not show any
      significant trends and/or variations for any of the sampling campaign, Kd values
      for each site increased with time. Furthermore, it was found that the Kd values
      decreased with distance from the headstream in the off-limits zone. Thus, the
      data acquired in this study give an overview of the radiological situation for
      Fukushima including temporal and spatial variation of radiocaesium in a natural
      riverine system, within a few years after the accident.

PMID- 24929978
TI  - Improvement and validation of a medium-term gpt delta rat model for predicting
      chemical carcinogenicity and underlying mode of action.
AB  - We have developed a new medium-term animal model, "GPG", in which an in vivo
      mutation assay in partially hepatectomized tissue and a tumor-promoting assay
      were performed. The tumor-promoting assay measures glutathione S-transferase
      placental form positive foci induced by diethylnitrosamine (DEN) in the residual
      tissue. Given that a limitation of the original protocol is the potential
      interaction between the test chemical and DEN, the present study establishes a
      modified protocol that includes a test chemical washout period. Using CYP2E1
      inhibitor and CYP1A or CYP2B inducers, a period of 2 weeks after cessation of
      exposure to the chemicals was confirmed to be sufficient to return their
      enzymatic activities to normal levels. Additionally, to avoid the effects of DEN
      on the pharmacokinetics of the test chemical, re-exposure to the test chemical
      started 1 week after DEN injection, in which tumor-promoting activities were
      clearly detected. Consequently, a modified protocol has been established with 2-
      and 1-week washout periods before and after DEN injection, respectively. The
      applicability of the modified protocol was demonstrated using the genotoxic
      hepatocarcinogen, estragole (ES), the genotoxic renal carcinogen, aristolochic
      acid (AA), and the non-genotoxic hepatocarcinogens, beta-naphthoflavone and
      barbital. Furthermore, the increase of cell cycle-related parameters in ES
      treated livers, but not in AA-treated livers, may indicate that the liver is not
      the carcinogenic target site of AA despite its genotoxic role. Thus, since
      various parameters related to carcinogenesis can be evaluated concurrently, the
      GPG model could be a rapid and reliable assay for the assessment of human cancer
      hazards.

PMID- 24929991
TI  - The role of each compartment in a two-compartment vertical flow reactor for
      ferruginous mine water treatment.
AB  - A vertical flow reactor (VFR) has been suggested for remediation of ferruginous
      mine drainage that passes down through an accreting bed of ochre. However, a VFR
      has a limited operation time until the system begins to overflow. In this study,
      a mathematical model was developed as a part of the effort to explore the
      operation of a VFR, showing dynamic changes in the head differences, ochre
      depths, and Fe(II)/Fe(III) concentrations in the effluent flow. The analysis
      showed that VFR operation time extended from 148.5 days to 163 days in an equally
      divided and to 168.4 days in asymmetrically (0.72:0.28) divided two-compartment
      VFR, suggesting that an optimum compartment ratio exists that maximizes the VFR
      operation time. A constant head filtration in the first compartment maximized
      filtration efficiency and thus prolonged VFR longevity in the two-compartment
      VFR. Fe(II) oxidation and ochre formation should be balanced with the
      permeability of the ochre bed to maximize the VFR operation time and minimize the
      residual Fe(II) in the effluent. Accelerated Fe(II) oxidation affected the
      optimum ratio of the compartment area and reduced the residual Fe(II) in the
      effluent. The VFR operation time can be prolonged significantly from 764 days to
      3620 days by increasing the rate of ochre formation, much more than by
      accelerating the Fe(II) oxidation. During the prolonged VFR operation, ochre
      formed largely in the first compartment, while overflowing mine water with
      reduced iron content was effectively filtered in the second compartment. These
      results not only provide a better understanding of VFR operation but also suggest
      the direction of evolution of two-compartment VFR toward a compact and highly
      efficient facility integrated with an aerated cascade and with automatic
      coagulant feeding. 

PMID- 24929992
TI  - Joel J. Alpert, MD (1930-2013).

PMID- 24929993
TI  - Editorial overview: development and regeneration: nervous system development and
      regeneration.

PMID- 24929994
TI  - Establishment and maintenance of a standardized glioma tissue bank: Huashan
      experience.
AB  - Cerebral glioma is the most common brain tumor as well as one of the top ten
      malignant tumors in human beings. In spite of the great progress on chemotherapy
      and radiotherapy as well as the surgery strategies during the past decades, the
      mortality and morbidity are still high. One of the major challenges is to explore
      the pathogenesis and invasion of glioma at various "omics" levels (such as
      proteomics or genomics) and the clinical implications of biomarkers for
      diagnosis, prognosis or treatment of glioma patients. Establishment of a
      standardized tissue bank with high quality biospecimens annotated with clinical
      information is pivotal to the solution of these questions as well as the drug
      development process and translational research on glioma. Therefore, based on
      previous experience of tissue banks, standardized protocols for sample collection
      and storage were developed. We also developed two systems for glioma patient and
      sample management, a local database for medical records and a local image
      database for medical images. For future set-up of a regional biobank network in
      Shanghai, we also founded a centralized database for medical records. Hence we
      established a standardized glioma tissue bank with sufficient clinical data and
      medical images in Huashan Hospital. By September, 2013, tissues samples from
      1,326 cases were collected. Histological diagnosis revealed that 73 % were
      astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic
      tumors, 4 % were ependymal tumors and 4 % were other central nervous system
      neoplasms.

PMID- 24929997
TI  - 'A very valuable fusion of classes': British professional and volunteer nurses of
      the First World War.
AB  - Public perceptions of the work of nurses and VAD-volunteers in the First World
      War have been heavily influenced by a small number of VAD-writings. The work of
      trained, professional nurses in supporting and supervised the work of VADs has
      been largely overlooked. This paper examines several of the writings of both
      volunteers and professionals, and emphasises the overlooked supervisory,
      managerial and clinical work of trained nurses. In this centenary year of the
      First World War's opening months, the paper also explores the ways in which the
      British mass-media--notably the BBC--have chosen to cling to a romantic image of
      the untrained nurse, whilst at the same time acknowledging the significance of
      trained, professional nursing.

PMID- 24929995
TI  - Purification of kavalactones from Alpinia zerumbet and their protective actions
      against hydrogen peroxide-induced cytotoxicity in PC12 cells.
AB  - This study found that fruit shells of shell ginger (Alpinia zerumbet) are a rich
      source of the kavalactones dihydro-5,6-dehydrokavain (DDK) and 5,6-dehydrokavain
      (DK). The fruit shell extraction with hexane resulted in good purity and higher
      yields of DDK and DK than did chloroform, ethanol, 10% ethanol, methanol or
      water. Additionally, this study examined the neuroprotective effects of DDK and
      DK against H2O2-induced cytotoxicity in PC12 cells and the possible molecular
      mechanisms involved. 16 h after stimulation with 400 MUM H2O2, the viability (MTT
      reduction) of PC12 cells decreased while membrane damage (LDH release) was
      noticeably increased. However, pretreatment for 6 h with DDK and DK (1 MUM, 5
      MUM, 10 MUM and 50 MUM) rescued PC12 cells from H2O2-induced cytotoxicity, as
      evidenced by decreased LDH release and increased cell viability. DDK and DK
      inhibit the MAPK family member p38, activate AKT, and reduce caspase-3 activity.
      DDK also reduced the oxidative status in H2O2-treated PC12 cells. Together, our
      data indicate that the A. zerumbet constituents, DDK and DK, exert a protective
      effect against oxidative stress-induced PC12 cell death and that the regulation
      of p-Akt and the p38 MAPK, and of oxidative states may be involved.

PMID- 24929996
TI  - Frailty and mortality or incident disability in institutionalized older adults:
      the FINAL study.
AB  - BACKGROUND: Little is known about frailty in institutionalized older adults, and
      there are few longitudinal studies on this topic. OBJECTIVES: To determine the
      association between frailty and mortality or incident disability in basic
      activities of daily living (BADL) in institutionalized Spanish older adults.
      DESIGN: Concurrent cohort study. SETTING: Two nursing homes, Vasco Nunez de
      Balboa and Paseo de la Cuba, in Albacete, Spain. PARTICIPANTS: Of the 324
      institutionalized adults older than 65 years enrolled at baseline, 21 (5.5%) were
      lost during the one-year follow-up. Of the 303 remaining, 63 (20.8%) died, 91
      (30.0%) developed incident disability, and 140 (49.2%) were free of both events.
      16 participants were not suitable for analysis due to incomplete data.
      MEASUREMENTS: Frailty was defined by the presence of three or more Fried
      criteria: unintentional weight loss, low energy, exhaustion, slowness, and low
      physical activity. Incident disability in BADL was considered when new onset
      disability in bathing, grooming, toileting, dressing, eating or transferring was
      detected with the Barthel index. Logistic regression models were constructed
      adjusted for age, sex, body mass index (BMI), previous Barthel index and
      Minimental State Examination (MMSE), and high comorbidity (Charlson index >=3).
      RESULTS: 287 participants with valid data. Mean age 84.2 (SD 6.8), with 187
      (65.2%) women. 199 (69.3%) were frail, and 72 (25.1%) had high comorbidity. Mean
      BMI 27.6 (SD 5.2), Barthel index 53.4 (SD 37.1), and MMSE 14.2 (SD 9.7). At
      follow-up, 43 (21.6%) frail participants and 15 (17.0%) non-frail ones died. 73
      (46.8%) frail participants and 16 (21.9%) non-frail ones developed incident
      disability in BADL (p<0.001). Frailty was associated with incident disability or
      mortality (OR 3.3; 95% CI 1.7-6.6) adjusted for all study covariables.
      CONCLUSION: In a cohort of institutionalized older adults, frailty was associated
      with mortality or incident disability in BADL.

PMID- 24929998
TI  - The Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) and Bipolar
      Adjective Scale (BAS): aspects of validity.
AB  - PURPOSE: In order to estimate instrument validity, attitudes toward stuttering
      measured by the newly developed Public Opinion Survey of Human Attributes
      Stuttering (POSHA-S) and the Woods and Williams (1976) semantic differential
      scale (referred to herein as the Bipolar Adjective Scale [BAS]) are compared in
      college students on one occasion as well as before and after coursework on
      fluency disorders. METHOD: Undergraduate and graduate students (n=321) from four
      universities filled out online versions of the POSHA-S and BAS. Two-thirds were
      speech-language pathology (SLP) majors; one-third were students in other majors.
      A subset of the SLP students (n=35) filled out the two instruments again after 8
      13 weeks of coursework on fluency disorders. RESULTS: Correlations between all
      ratings of the POSHA-S and BAS were run for the 321 students. Only 26% of the
      correlations were statistically significant (R >= +/- 0.129), and the large
      majority of these reflected small relationships. POSHA-S ratings were correlated
      with up to 77% of the items of the BAS while BAS items were correlated with up to
      45% of the POSHA-S ratings. After coursework on stuttering, students' attitudes
      improved on both instruments, but more on the POSHA-S than the BAS. CONCLUSIONS:
      Greater evidence of discriminant validity than convergent validity characterized
      the POSHA-S and BAS. Both measures showed improved attitudes after fluency
      disorders coursework, but more so for the POSHA-S, confirming previous reports of
      construct validity. The POSHA-S taps relevant constructs not included in the BAS,
      which provide advantages for intracultural, international, and other comparisons
      of public attitudes toward stuttering. LEARNING OUTCOMES: The reader will be able
      to: (1) describe differentiating characteristics of the POSHA-S and BAS as
      measures of public attitudes toward stuttering, (2) describe the overlap and lack
      of overlap in the constructs measured by POSHA-S and BAS, (3) describe
      discriminant versus convergent validity and (4) describe advantages of the POSHA
      S and BAS in various types of comparative studies of stuttering attitudes.

PMID- 24929999
TI  - Hepatoprotective effects of Ger-Gen-Chyn-Lian-Tang in thioacetamide-induced
      fibrosis in mice.
AB  - BACKGROUND: Many researchers have focused on developing traditional herbal
      medicines as pharmacological medicines to treat hepatic fibrosis. In this study,
      we evaluated the possible mechanism of Ger-Gen-Chyn-Lian-Tang (GGCLT) on
      thioacetamide (TAA)-induced hepatic injury in mice. METHODS: Hepatic fibrosis
      mice were established by intraperitoneal injection with TAA (100 mg/kg, 3
      times/week), and treated with daily oral administration of 30 mg/kg, 100 mg/kg,
      and 300 mg/kg of GGCLT for 6 weeks. There were 40 mice randomly assigned to
      control, TAA and TAA+GGCLT groups. When the experiment was completed, Masson's
      trichrome staining was used to measure the degree of liver fibrosis. Hepatic
      fibrosis molecules were assessed by Western blot and real-time polymerase chain
      reaction. Hepatic glutathione levels, matrix metalloproteinase (MMP-2 and MMP-9),
      and hydroxyproline were also measured. RESULTS: Treatment with GGCLT
      significantly reduced the toxicity of TAA and exhibited effective
      hepatoprotective activity. The mechanism of the hepatoprotective effect of GGCLT
      is proposed to be by normalizing oxidative stress. Additionally, the data of
      fibrotic areas, expression of procollagen III, and MMP2 and 9 mRNA levels in the
      TAA+GGCLT group were much lower than those in the TAA group (p < 0.05).
      Furthermore, the upregulation of hepatic protein levels of nuclear factor-kappaB,
      transforming growth factor (TGF)-beta receptor-1, and smooth muscle alpha-actin
      induced by TAA was significantly inhibited after GGCLT treatment. CONCLUSION:
      GGCLT can efficiently ameliorate hepatic fibrosis by its inhibitory effects on
      the intrahepatic oxidative stress in TAA mice model. The antioxidant properties
      afforded by GGCLT may be attributed to its modulation on TGF-beta/TGFbeta
      receptor signaling through the downregulation of integrated signal pathways
      involving smooth muscle alpha-actin and lipid peroxidation.

PMID- 24930000
TI  - Surgery for parapneumonic pleural empyema--What influence does the rising
      prevalence of multimorbidity and advanced age has on the current outcome?
AB  - OBJECTIVE: Pleural empyema is a critical condition. In the western world the
      share of sufferers with multiple comorbidities and advanced age is rapidly
      increasing. METHODS: This retrospective study comprises all patients who
      underwent surgery for parapneumonic pleural empyema at a major center for
      thoracic surgery in Germany between January 2006 and April 2013. RESULTS: A total
      of 335 patients (mean age 60.4 years) were included. The average ASA grade was
      2.8. Empyema stage 1, 2 and 3 (classification of the American Thoracic Society)
      was encountered in 30, 230 and 75 cases, respectively. The most common
      comorbidities were cardiac disorders (124), diabetes mellitus (76), COPD (66) and
      alcoholism (54). The mean Charlson index of comorbidity score was 2. Minimally
      invasive surgery was feasible in 290 cases. A total of 88 patients sustained
      pulmonary sepsis. The overall mortality was 29/335 (8.7%). The occurrence of
      pulmonary sepsis (OR: 17.95; 95% CI: 6.38-62.69; p < 0.001), respiratory failure
      (OR: 23.08; 95% CI: 8.52-73.35; p < 0.001) and acute renal failure (OR: 8.20; 95%
      CI: 3.18-20.80; p < 0.001) and Charlson score >= 3 (OR: 6.65; 95% CI: 2.76-17.33;
      p < 0.001) were associated with higher mortality. On the other hand, very elderly
      sufferers (>=80 years) showed neither higher odds for pulmonary sepsis (OR: 0.78)
      nor for fatal outcome (OR: 0.92; 95% CI: 0.22-2.86; p = 1). CONCLUSIONS:
      Parapneumonic pleural empyema is still associated with considerable morbidity and
      mortality. Pre-existing comorbidity, the occurrence of pulmonary sepsis and
      sepsis related complications have a determining influence on the results whereas
      advanced age itself shows no higher risk for adverse outcome. Further improvement
      seems achievable by earlier surgical intervention before the onset of pulmonary
      sepsis.

PMID- 24930001
TI  - Anatomical conditions of the posterior pelvic ring regarding bisegmental
      transverse sacroiliac screw fixation: a 3D morphometric study of 125 pelvic CT
      datasets.
AB  - INTRODUCTION: Sacroiliac (SI) screws are used for osteosynthesis in unstable
      posterior pelvic ring injuries. In the cases of "sacral dysplasia", in which the
      elevated upper sacrum does not allow a secure SI screw insertion into the S1
      level, the S2 segment must be used to achieve stable fixation. The bone quality
      of the S2 segment is thinner compared to that of the S1 vertebra and may cause
      biomechanical weakness. An additional SI screw insertion into the S3 level may
      improve stability. With respect to the anatomical conditions of the posterior
      pelvic ring, there have been no anatomical investigations to date regarding SI
      screw placement into the third sacral segment. MATERIALS AND METHODS: CT raw
      datasets from 125 patients (o59 years, o172 cm, o76 kg) were post-processed using
      Amira 5.2 software to generate 3D pelvic models. A program code implemented in
      C++ computed a transverse bone corridor for the first, second and third sacral
      segments for a typical SI screw diameter of 7.3 mm. Volume, sagittal cross
      section, iliac entrance area and length of the determined screw corridors were
      measured. A confidence interval of 95 % was assumed (p < 0.05). RESULTS: The
      fully automatic computation revealed a possible transverse insertion for one 7.3
      mm screw in the third sacral segment in 30 cases (24 %). The rate (60 %) of
      feasible S3 screw placements in the cases of sacral dysplasia (n = 25) is
      significantly higher compared to that (15 %) of "normal" sacra (n = 100). With
      regard to the existence of transverse iliosacroiliac corridors as a function of
      sacral position in between the adjacent iliac bone bilaterally, a new
      classification of three different shape conditions can be made: caudad,
      intermediate minor, intermediate major, and cephalad sacrum. Gender, age, body
      height and body weight had no statistically significant influence on either
      possible screw insertion or on the calculated data of the corridors (p > 0.05).
      CONCLUSION: SI screw insertion into the third sacral level deserves discussion in
      the cases of sacral dysplasia. Biomechanical and practical utility must be
      verified.

PMID- 24930002
TI  - Rare biscoumarin derivatives and flavonoids from Hypericum riparium.
AB  - Hypericum riparium A. Chev. is a Cameroonian medicinal plant belonging to the
      family Guttiferae. Chemical investigation of the methanol extract of the stem
      bark of H. riparium led to the isolation of four natural products, 7,7'-dihydroxy
      6,6'-biscoumarin (1), 7,7'-dihydroxy-8,8'-biscoumarin (2), 7-methoxy-6,7'
      dicoumarinyl ether (3), 2'-hydroxy-5'-(7"-methoxycoumarin-6"-yl)-4'
      methoxyphenylpropanoic acid (4), together with one known 7,7'-dimethoxy-6,6'
      biscoumarin (5), two flavones, 2'-methoxyflavone (6) and 3'-methoxy flavone (7),
      and two steroids, stigmast-4-en-3-one (8) and ergosta-4,6,8,22-tetraen-3-one (9).
      In addition, tetradecanoic acid (10), n-pentadecanoic acid (11), hexadecanoic
      acid (12), cis-10-heptadecenoic acid (13), octadecanoic acid (14) campesterol
      (15), stigmasterol (16), beta-sitosterol (17), stigmastanol (18), beta-eudesmol
      (19), 1-hexadecanol (20), and 1-octadecanol (21) were identified by GC-MS
      analysis. Compound 4 consists of a phenylpropanoic acid derivative fused with a
      coumarin unit, while compounds 2 and 3 are rare members of C8-C8' and C7-O-C6
      linked biscoumarins. Their structures were elucidated by UV, IR, extensive 1D-
      and 2D-NMR experiments and electrospray (ESI) high resolution mass spectrometry
      (MS) including detailed MS/MS studies. This is the first report on the isolation
      of biscoumarins from the genus Hypericum, although simple coumarin derivatives
      have been reported from this genus in the literature. The cytotoxic activities of
      compounds 2-5 were evaluated against the human prostate cancer cell line PC-3 and
      the colon cancer cell line HT-29. They do not exhibit any significant cytotoxic
      activity. 

PMID- 24930003
TI  - PTSD in the U.S. military, and the politics of prevalence.
AB  - Despite the long-standing codification of posttraumatic stress disorder (PTSD) as
      a mental disorder, the diagnosis is a controversial one whose legitimacy is at
      times disputed, particularly in U.S. military contexts (e.g., McNally and Frueh
      2013; McNally, 2003, 2007). These disputes often manifest in a struggle over
      prevalence rates. Utilizing data from in-depth interviews and relying on
      situational analysis methodology (Clarke, 2005), I highlight this struggle in the
      wake of a decade of U.S.-led war in Afghanistan and Iraq. I focus on the objects
      of contestation employed by public officials, veterans' advocates, and
      researchers to make or refute claims about PTSD prevalence. These objects of
      contestation include the diagnostic category and criteria; screening tools,
      procedures, or systems; and the individuals who express symptoms of the disorder.
      Based on these claims, I make two key interrelated assertions. First, PTSD is
      viewed by some public officials as an overly generalized or invalid diagnostic
      category that is often induced in or falsified by veterans or servicemembers. As
      such, PTSD is perceived by these stakeholders to be over-diagnosed. Compounding
      these perceptions are beliefs that PTSD is costly and negatively impacts military
      duty performance, and thus overall manpower. Second, there exist perceptions,
      largely on the part of veterans' advocates but also some public officials, that
      many servicemembers and veterans are not seeking treatment (and thus, a
      diagnosis) when they experience symptoms of PTSD. Thus, PTSD is perceived by
      these stakeholders to be under-diagnosed. Paradoxically, some public officials
      make both claims: that PTSD is over-diagnosed and under-diagnosed. I conclude by
      exploring the implications of these findings. 

PMID- 24930004
TI  - The morphometric development and clinical importance of the hyoid bone during the
      fetal period.
AB  - It was aimed that the morphometric development of the hyoid bone throughout the
      fetal period be anatomically researched and its clinical importance be evaluated.
      A total of 90 human fetuses (44 male, 46 female) whose ages varied between 18 and
      40 gestational weeks and without an external pathology or anomaly were involved
      in the study. The fetuses were divided into groups according to gestational weeks
      and trimesters. In the wake of making the general external measurements of
      fetuses, the neck dissection was performed. Following the localization of the
      hyoid bone, the morphometric parameters pertaining to the hyoid bone were
      measured. The averages of the measured parameters according to the gestational
      weeks, trimesters and months, and their standard deviations were determined.
      There was a significant correlation between the measured parameters and the
      gestational age (p < 0.001). Between the genders, there was no difference among
      the other parameters, except for those regarding the distance between the hyoid
      bone and columna vertebralis, the hyoid bone corpus length, the hyoid bone right
      cornu majus initial width, the hyoid bone left cornu majus initial width, and the
      upper distance between the hyoid bone cornu majus (es) (p > 0.001). We are of the
      opinion that the data obtained during our study will be of use to forensic
      physicians and the involved clinicians in the evaluation of the development of
      the hyoid bone area during the fetal period, and in clinical studies and
      practices. 

PMID- 24930005
TI  - The superior ophthalmic vein: delineation with high-resolution magnetic resonance
      imaging.
AB  - OBJECTIVE: To delineate the superior ophthalmic vein (SOV) with high-resolution
      magnetic resonance (MR) imaging. METHODS: This retrospective study enrolled 302
      consecutive outpatients, 101 patients, 51 males and 50 females, who underwent
      coronal T2-weighted imaging and 201 patients, 99 males and 102 females, who
      underwent three-dimensional (3D) phase-contrast (PC) MR angiography. RESULTS:
      Coronal T2-weighted imaging clearly delineated the intraorbital course of SOV on
      serial images in all 101 subjects. The SOV could be topographically divided into
      three segments in relation to the superior rectus muscle. The SOV crossed over
      the optic nerve at the level of the anterior ethmoidal foramina in 87% of right
      orbits and 71% of left orbits. The mean outer diameter of the SOV at the crossing
      point was 1.7 mm on both sides, but the SOVs were asymmetric in the same
      individual in 75% of the subjects. 3D PC MR angiography showed that the bilateral
      SOVs were symmetrical in 16% of subjects, larger in the right orbit in 18%, and
      larger in the left orbit in 13%, and were unidentified in 52%. The SOV showed a
      consistent lateral course to the ophthalmic artery. CONCLUSIONS: The SOV
      consistently courses lateral to the ophthalmic artery, but tends to show
      bilateral asymmetry in the outer diameter. The superior rectus muscle, anterior
      ethmoidal foramen, and anterior ethmoidal artery are valuable landmarks to
      identify the SOV during transcranial orbital surgery. Combination of high
      resolution MR imaging and 3D PC MR angiography is useful for delineating the SOV.

PMID- 24930007
TI  - URG11 predicts poor prognosis of pancreatic cancer by enhancing epithelial
      mesenchymal transition-driven invasion.
AB  - The poor prognosis and high recurrent rate of pancreatic cancer (PC) necessitates
      the discovery of new predictive markers of PC invasion and prognosis. In this
      study, we evaluated the expression pattern of up-regulated gene 11 (URG11) in a
      tissue microarray with 18 pairs of PC and adjacent normal tissues. It was shown
      that URG11 was significantly up-regulated in PC tissues. High expression levels
      of URG11 were detected in all PC specimens, but were rarely detected in adjacent
      non-tumorous tissues. In addition, high expression of URG11 was correlated to
      poor prognosis. Furthermore, it was discovered that URG11 was correlated to
      epithelial-mesenchymal transition (EMT) markers and clinical pathological
      parameters indicative of high PC invasion, while knockdown of URG11 significantly
      changed the expression pattern of EMT markers and decreased the invasion of PC
      cells. These findings indicate that URG11 might enhance the invasion of PC by
      inducing EMT and thus lead to poor PC prognosis. Thus, URG11 has the potential to
      be a new predictive biomarker of PC invasion and prognosis, which may help in the
      diagnosis and treatment of PC patients. 

PMID- 24930006
TI  - High expression of miR-21 in triple-negative breast cancers was correlated with a
      poor prognosis and promoted tumor cell in vitro proliferation.
AB  - The triple-negative breast cancer (TNBC), with a particularly poor prognosis, is
      increasingly recognized as heterogeneous in molecular signatures. MicroRNA
      expression profiles have been used for the classification and prognostication of
      breast cancer, numerous significantly upregulated microRNAs, i.e. miR-21, have
      been verified oncogenic in non-TNBCs. In present study, we determined the miR-21
      levels in TNBC specimens, and TNBC cell levels in vitro, and then identified the
      role of miR-21 on tumor cell proliferation, apoptosis, and then identified PTEN
      as the possible target of the microRNA. It was shown that miR-21 expression is
      upregulated generally, and heterogeneous in TNBC specimens, posing a correlation
      with poor prognosis for TNBC patients. Further results demonstrated that the
      upregulated miR-21 promoted the tumor proliferation and inhibited cell apoptosis
      in vitro. And pro-apoptotic PTEN had been shown being targeted and downregulated.
      Therefore, our finding emphasized the oncogenic role of miR-21 in TNBC. 

PMID- 24930008
TI  - Observed management practices in relation to the risk of infection with
      paratuberculosis and to the spread of Mycobacterium avium subsp. paratuberculosis
      in Swiss dairy and beef herds.
AB  - BACKGROUND: Many studies have been conducted to define risk factors for the
      transmission of bovine paratuberculosis, mostly in countries with large herds.
      Little is known about the epidemiology in infected Swiss herds and risk factors
      important for transmission in smaller herds. Therefore, the presence of known
      factors which might favor the spread of paratuberculosis and could be related to
      the prevalence at animal level of fecal shedding of Mycobacterium avium subsp.
      paratuberculosis were assessed in 17 infected herds (10 dairy, 7 beef).
      Additionally, the level of knowledge of herd managers about the disease was
      assessed. In a case-control study with 4 matched negative control herds per
      infected herd, the association of potential risk factors with the infection
      status of the herd was investigated. RESULTS: Exposure of the young stock to
      feces of older animals was frequently observed in infected and in control herds.
      The farmers' knowledge about paratuberculosis was very limited, even in infected
      herds. An overall prevalence at animal level of fecal shedding of Mycobacterium
      avium subsp. paratuberculosis of 6.1% was found in infected herds, whereby
      shedders younger than 2 years of age were found in 46.2% of the herds where the
      young stock was available for testing. Several factors related to contamination
      of the heifer area with cows' feces and the management of the calving area were
      found to be significantly associated with the within-herd prevalence. Animal
      purchase was associated with a positive herd infection status (OR = 7.25, p =
      0.004). CONCLUSIONS: Numerous risk factors favoring the spread of Mycobacterium
      avium subsp. paratuberculosis from adult animals to the young stock were observed
      in infected Swiss dairy and beef herds, which may be amenable to improvement in
      order to control the disease. Important factors were contamination of the heifer
      and the calving area, which were associated with higher within-herd prevalence of
      fecal shedding. The awareness of farmers of paratuberculosis was very low, even
      in infected herds. Animal purchase in a herd was significantly associated with
      the probability of a herd to be infected and is thus the most important factor
      for the control of the spread of disease between farms.

PMID- 24930009
TI  - Determination of sample size for a multi-class classifier based on single
      nucleotide polymorphisms: a volume under the surface approach.
AB  - BACKGROUND: Data on single-nucleotide polymorphisms (SNPs) have been found to be
      useful in predicting phenotypes ranging from an individual's class membership to
      his/her risk of developing a disease. In multi-class classification scenarios,
      clinical samples are often limited due to cost constraints, making it necessary
      to determine the sample size needed to build an accurate classifier based on
      SNPs. The performance of such classifiers can be assessed using the Area Under
      the Receiver Operating Characteristic (ROC) Curve (AUC) for two classes and the
      Volume Under the ROC hyper-Surface (VUS) for three or more classes. Sample size
      determination based on AUC or VUS would not only guarantee an overall correct
      classification rate, but also make studies more cost-effective. RESULTS: For
      coded SNP data from D(>=2) classes, we derive an optimal Bayes classifier and a
      linear classifier, and obtain a normal approximation to the probability of
      correct classification for each classifier. These approximations are then used to
      evaluate the associated AUCs or VUSs, whose accuracies are validated using Monte
      Carlo simulations. We give a sample size determination method, which ensures that
      the difference between the two approximate AUCs (or VUSs) is below a pre
      specified threshold. The performance of our sample size determination method is
      then illustrated via simulations. For the HapMap data with three and four
      populations, a linear classifier is built using 92 independent SNPs and the
      required total sample sizes are determined for a continuum of threshold values.
      In all, four different sample size determination studies are conducted with the
      HapMap data, covering cases involving well-separated populations to poorly
      separated ones. CONCLUSION: For multi-classes, we have developed a sample size
      determination methodology and illustrated its usefulness in obtaining a required
      sample size from the estimated learning curve. For classification scenarios, this
      methodology will help scientists determine whether a sample at hand is adequate
      or more samples are required to achieve a pre-specified accuracy. A PDF manual
      for R package "SampleSizeSNP" is given in Additional file 1, and a ZIP file of
      the R package "SampleSizeSNP" is given in Additional file 2.

PMID- 24930010
TI  - Assessment of iron chelates efficiency for photo-Fenton at neutral pH.
AB  - In this study, homogeneous photo-Fenton like at neutral pH was applied to remove
      sulfamethoxazole from water. The process was performed using different chelating
      agents in order to solubilize iron in a neutral water solution. The chelating
      agents tested were: ethylenediaminetetraacetic acid (EDTA); nitrilotriacetic acid
      (NTA); oxalic acid (OA) and tartaric acid (TA). The iron leaching was monitored
      over reaction time to evaluate the chelates stability and their resistance to HO.
      and UV-A radiation. Chelates of EDTA and NTA presented more stability than OA and
      TA, which also confirmed their higher efficiency. Total Organic Carbon (TOC)
      analyses were also performed to evaluate the contribution in terms of solution
      contamination related to the use of chelating agents. The better properties of
      biodegradability in respect of EDTA combined with better efficiency in terms of
      microcontaminant removal and the smallest TOC contribution indicate that NTA
      could represent a useful option to perform photo-Fenton processes at neutral pH. 

PMID- 24930011
TI  - A national investigation of the prevalence and diversity of thermophilic
      Campylobacter species in agricultural watersheds in Canada.
AB  - The occurrence and diversity of thermophilic Campylobacter species (C. jejuni,
      coli, and lari) were studied in water samples from four river basins located
      across Canada. These basins located in Quebec (Bras d'Henri), Alberta (Oldman),
      Ontario (South Nation), and British Columbia (Sumas) represented some of the most
      intensive farming areas in Canada for hog, beef cattle, dairy cattle, and
      poultry, respectively. This study analyzed 769 water samples collected from 23
      monitoring sites with agricultural influence, and four reference sites with
      limited or no agricultural influence. Water samples were collected bi-weekly over
      two years and analyzed for Campylobacter using a semi-quantitative minimum
      probable number (MPN) enrichment protocol. Putative isolates were confirmed by
      genus- and species-specific multiplex polymerase chain reaction (PCR) assays. A
      total of 377 (49%) water samples were positive for campylobacters with 355
      samples having a cell density ranging from 4 to 4000 MPN L(-1). Campylobacters
      were more common at agricultural than reference sites in each river basin,
      although this difference was not significant in the Oldman and South Nation (p >
      0.05). Campylobacter was significantly more common in the Bras d'Henri and Sumas
      (63%) compared to the South Nation (45%) and Oldman (33%) River basins (p <
      0.05). C. jejuni, C. coli and C. lari were detected in each river basin, and
      these species occurred in 45% (n = 168), 34% (n = 128) and 19% (n = 73), of all
      Campylobacter positive samples, respectively. The remaining Campylobacter
      positive water samples without these three species (n = 67; 18%) were identified
      as other Campylobacter species. C. jejuni was the predominant species occurring
      in the Sumas, Oldman and South Nation River basins. However, in the Bras d'Henri
      River basin with intensive hog production, C. coli was the predominant species.
      This study found campylobacters to be common in some agricultural systems with
      intensive livestock farming activities, and different river basins could have
      strikingly different profiles of either C. jejuni or C. coli as the predominant
      waterborne thermophilic Campylobacter species.

PMID- 24930012
TI  - Blockade of PKCbeta protects against remote organ injury induced by intestinal
      ischemia and reperfusion via a p66shc-mediated mitochondrial apoptotic pathway.
AB  - Intestinal ischemia-reperfusion (I/R) is a serious clinical dilemma with high
      morbidity and mortality. Remote organ damage, especially acute lung injury and
      liver injury are common complications that contribute to the high mortality rate.
      We previously demonstrated that activation of PKCbetaII is specifically involved
      in the primary injury of intestinal I/R. Considering the tissue-specific features
      of PKC activation, we hypothesized that some kind of PKC isoform may play
      important roles in the progression of secondary injury in the remote organ. Mice
      were studied in in vivo model of intestinal I/R. The activation of PKC isoforms
      were screened in the lung and liver. Interestingly, we found that PKCbetaII was
      also activated exclusively in the lung and liver after intestinal I/R. PKCbetaII
      suppression by a specific inhibitor, LY333531, significantly attenuated I/R
      induced histologic damage, inflammatory cell infiltration, oxidative stress, and
      apoptosis in these organs, and also alleviated systemic inflammation. In
      addition, LY333531 markedly restrained p66shc activation, mitochondrial
      translocation, and binding to cytochrome-c. These resulted in the decrease of
      cytochrome-c release and caspase-3 cleavage, and an increase in glutathione and
      glutathione peroxidase. These data indicated that activated PKC isoform in the
      remote organ, specifically PKCbetaII, is the same as that in the intestine after
      intestinal I/R. PKCbetaII suppression protects against remote organ injury, which
      may be partially attributed to the p66shc-cytochrome-c axis. Combined with our
      previous study, the development of a specific inhibitor for prophylaxis against
      intestinal I/R is promising, to prevent multiple organ injury. 

PMID- 24930013
TI  - Optimised mounting conditions for poly (ether sulfone) in radiation detection.
AB  - Poly (ether sulfone) (PES) is a candidate for use as a scintillation material in
      radiation detection. Its characteristics, such as its emission spectrum and its
      effective refractive index (based on the emission spectrum), directly affect the
      propagation of light generated to external photodetectors. It is also important
      to examine the presence of background radiation sources in manufactured PES.
      Here, we optimise the optical coupling and surface treatment of the PES, and
      characterise its background. Optical grease was used to enhance the optical
      coupling between the PES and the photodetector; absorption by the grease of short
      wavelength light emitted from PES was negligible. Diffuse reflection induced by
      surface roughening increased the light yield for PES, despite the high effective
      refractive index. Background radiation derived from the PES sample and its
      impurities was negligible above the ambient, natural level. Overall, these
      results serve to optimise the mounting conditions for PES in radiation detection.

PMID- 24930014
TI  - Tomato SlMKK2 and SlMKK4 contribute to disease resistance against Botrytis
      cinerea.
AB  - BACKGROUND: Mitogen-activated protein kinase (MAPK) cascades are highly conserved
      signaling modules that mediate the transduction of extracellular stimuli via
      receptors/sensors into intracellular responses and play key roles in plant
      immunity against pathogen attack. However, the function of tomato MAPK kinases,
      SlMKKs, in resistance against Botrytis cinerea remains unclear yet. RESULTS: A
      total of five SlMKK genes with one new member, SlMKK5, were identified in tomato.
      qRT-PCR analyses revealed that expression of SlMKK2 and SlMKK4 was strongly
      induced by B. cinerea and by jasmonic acid and ethylene precursor 1-amino
      cyclopropane-1-carboxylic acid. Virus-induced gene silencing (VIGS)-based
      knockdown of individual SlMKKs and disease assays identified that SlMKK2 and
      SlMKK4 but not other three SlMKKs (SlMKK1, SlMKK3 and SlMKK5) are involved in
      resistance against B. cinerea. Silencing of SlMKK2 or SlMKK4 resulted in reduced
      resistance to B. cinerea, increased accumulation of reactive oxygen species and
      attenuated expression of defense genes after infection of B. cinerea in tomato
      plants. Furthermore, transient expression of constitutively active
      phosphomimicking forms SlMKK2DD and SlMKK4DD in leaves of Nicotiana benthamiana
      plants led to enhanced resistance to B. cinerea and elevated expression of
      defense genes. CONCLUSIONS: VIGS-based knockdown of SlMKK2 and SlMKK4 expression
      in tomato and gain-of-function transient expression of constitutively active
      phosphomimicking forms SlMKK2DD and SlMKK2DD in N. benthamiana demonstrate that
      both SlMKK2 and SlMKK4 function as positive regulators of defense response
      against B. cinerea.

PMID- 24930017
TI  - Excellence in vascular surgery: maintaining high standards.

PMID- 24930016
TI  - Applicability of global positioning system for the assessment of walking ability
      in patients with arterial claudication.
AB  - OBJECTIVE: This study determined for the first time the clinical applicability of
      a global positioning system (GPS)-monitored community-based walking ability
      assessment in a large cohort of patients with peripheral artery disease (PAD).
      METHODS: A multicenter study was conducted among PAD patients who complained of
      intermittent claudication. Patients equipped with a GPS device performed a
      community-based outdoor walk. We determined the number of technically
      satisfactory GPS recordings (attempt No. 1). Patients with unsatisfactory GPS
      recordings were asked to perform a second attempt (attempt No. 2). From the
      satisfactory recordings obtained after attempts No. 1 and No. 2, we analyzed
      several GPS parameters to provide clinical information on the patients' walking
      ability. Results are reported as median (interquartile range). RESULTS: A total
      of 218 patients performed an outdoor walk. GPS recordings were technically
      satisfactory in 185 patients (85%) and in 203 (93%) after attempts No. 1 and No.
      2, respectively. The highest measured distance between two stops during community
      walking was 678 m (IQR, 381-1333 m), whereas self-reported maximal walking
      distance was 250 m (IQR, 150-400 m; P < .001). Walking speed was 3.6 km/h (IQR,
      3.1-3.9 km/h), with few variations during the walk. Among the patients who had to
      stop during the walk, the stop durations were <10 minutes in all but one
      individual. CONCLUSIONS: GPS is applicable for the nonsupervised multicenter
      recording of walking ability in the community. In the future, it may facilitate
      objective community-based assessment of walking ability, allow for the adequate
      monitoring of home-based walking programs, and for the study of new dimensions of
      walking in PAD patients with intermittent claudication.

PMID- 24930015
TI  - Distinct patterns of diversity, population structure and evolution in the AMA1
      genes of sympatric Plasmodium falciparum and Plasmodium vivax populations of
      Papua New Guinea from an area of similarly high transmission.
AB  - BACKGROUND: As Plasmodium falciparum and Plasmodium vivax co-exist in most
      malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in
      these areas must target both species in order to succeed. Population genetic
      analyses can predict the effectiveness of interventions including vaccines, by
      providing insight into patterns of diversity and evolution. The aim of this study
      was to investigate the population genetics of leading malaria vaccine candidate
      AMA1 in sympatric P. falciparum and P. vivax populations of Papua New Guinea
      (PNG), an area of similarly high prevalence (Pf = 22.3 to 38.8%, Pv = 15.3 to
      31.8%). METHODS: A total of 72 Pfama1 and 102 Pvama1 sequences were collected
      from two distinct areas, Madang and Wosera, on the highly endemic PNG north
      coast. RESULTS: Despite a greater number of polymorphic sites in the AMA1 genes
      of P. falciparum (Madang = 52; Wosera = 56) compared to P. vivax (Madang = 36,
      Wosera = 34), the number of AMA1 haplotypes, haplotype diversity (Hd) and
      recombination (R) was far lower for P. falciparum (Madang = 12, Wosera = 20; Hd
      <=0.92, R <=45.8) than for P. vivax (Madang = 50, Wosera = 38; Hd = 0.99, R =
      <=70.9). Balancing selection was detected only within domain I of AMA1 for P.
      vivax, and in both domains I and III for P. falciparum. CONCLUSIONS: Higher
      diversity in the genes encoding P. vivax AMA1 than in P. falciparum AMA1 in this
      highly endemic area has important implications for development of AMA1-based
      vaccines in PNG and beyond. These results also suggest a smaller effective
      population size of P. falciparum compared to P. vivax, a finding that warrants
      further investigation. Differing patterns of selection on the AMA1 genes indicate
      that critical antigenic sites may differ between the species, highlighting the
      need for independent investigations of these two leading vaccine candidates.

PMID- 24930019
TI  - Neurologic status on presentation to a Heart Attack Centre: a predictor of
      recovery or more aptly, a predictor of injury?

PMID- 24930018
TI  - Vitamin D and kidney transplant outcomes: a protocol for a systematic review and
      meta-analysis.
AB  - BACKGROUND: Patients with end-stage renal disease who receive kidney transplants
      have improved survival and quality of life compared to patients on dialysis.
      Unfortunately, transplant patients often have a low vitamin D concentration,
      which has well-known effects on calcium and bone metabolism. The effect of
      vitamin D on other indicators of transplant function, such as glomerular
      filtration rate and acute rejection, remains unknown. METHODS/DESIGN: We will
      conduct a systematic review of vitamin D status and outcomes after kidney
      transplantation. The primary objective is to assess the relationship between
      vitamin D and graft function using measured glomerular filtration rate (GFR) or
      estimated GFR from serum creatinine concentrations. Secondary outcomes will
      include acute rejection, chronic allograft nephropathy, proteinuria and graft
      loss. We will search MEDLINE, EMBASE, AMED and CINAHL for randomized and
      observational studies on adult renal transplant patients who received vitamin D
      supplementation or had serum vitamin D concentration measured. We will report
      study quality using the Cochrane Risk Assessment Tool for randomized controlled
      trials and the Newcastle-Ottawa Scale for observational studies. Quality across
      studies will be assessed using the GRADE approach. If pooling is deemed
      appropriate, we will perform meta-analyses using standard techniques for
      continuous and discrete variables, depending on the outcome. The results of this
      review may inform guideline development for vitamin D supplementation in renal
      transplant patients and highlight areas for further research. SYSTEMATIC REVIEW
      REGISTRATION PROSPERO: CRD42013006464.

PMID- 24930020
TI  - Controlling entropy to tune the functions of intrinsically disordered regions.
AB  - Intrinsically disordered regions (IDRs) are fundamental units of protein function
      and regulation. Despite their inability to form a unique stable tertiary
      structure in isolation, many IDRs adopt a defined conformation upon binding and
      achieve their function through their interactions with other biomolecules.
      However, this requirement for IDR functionality seems to be at odds with the high
      entropic cost they must incur upon binding an interaction partner. How is this
      seeming paradox resolved? While increasing the enthalpy of binding is one
      approach to compensate for this entropic cost, growing evidence suggests that
      inherent features of IDRs, for instance repeating linear motifs, minimise the
      entropic cost of binding. Moreover, this control of entropic cost can be
      carefully modulated by a range of regulatory mechanisms, such as alternative
      splicing and post-translational modifications, which enable allosteric
      communication and rheostat-like tuning of IDR function. In that sense, the high
      entropic cost of IDR binding can be advantageous by providing tunability to
      protein function. In addition to biological regulatory mechanisms, modulation of
      entropy can also be controlled by environmental factors, such as changes in
      temperature, redox-potential and pH. These principles are extensively exploited
      by a number of organisms, including pathogens. They can also be utilised in
      bioengineering, synthetic biology and in pharmaceutical applications such as
      increasing bioavailability of protein therapeutics. 

PMID- 24930021
TI  - Segmented negative-strand RNA viruses and RIG-I: divide (your genome) and rule.
AB  - The group of negative-stranded RNA viruses (NSVs) with a segmented genome
      comprises pathogens like influenza virus (eight segments), Rift Valley fever
      virus and Hantavirus (three segments), or Lassa virus (two segments).
      Partitioning the genome allows rapid evolution of new strains by reassortment.
      Each segment carries a short double-stranded (ds) 'panhandle' structure which
      serves as promoter. Similar dsRNA structures, however, represent the optimal
      ligand for RIG-I, a cytoplasmic pathogen sensor of the antiviral interferon
      response. Thus, segmenting a virus genome can entail an increased RIG-I
      sensitivity. Here, we outline the astonishingly diverse and efficient strategies
      by which segmented NSVs are compensating for the elevated number of RIG-I ligands
      in their genome. 

PMID- 24930022
TI  - Effects of management practices on yield and quality of milk from smallholder
      dairy units in urban and peri-urban Morogoro, Tanzania.
AB  - A longitudinal study design was used to assess the management, chemical
      composition of cows' milk and quantify the microbial load of raw milk produced at
      farm level. Data were collected between December 2010 and September 2011 in
      Morogoro municipality. Milk samples were collected once every month and analysed
      for butter fat (BF), crude protein (CP), total solids (TS) and solids non-fat
      (SNF). Total bacterial count (TBC) and coliform counts (CC) were normalized by
      log transformation. The average milk yield was 7.0 l/day and was not influenced
      by feeding systems and breeds. Dairy cows owned by people who had no regular
      income produced more milk than government employees and retired officers. Means
      of BF, TS, SNF and CP were similar in different feeding systems. Wet season had
      significantly higher TBC (5.9 log10 cfu/ml) and CC (2.4 log10 cfu/ml) but feeding
      systems had no effect. Stocking density influenced TBC but not CC. It can be
      concluded that dairy cows produced low milk yield and its quality was poor. 

PMID- 24930023
TI  - Modeling virtual organizations with Latent Dirichlet Allocation: a case for
      natural language processing.
AB  - This paper explores a variety of methods for applying the Latent Dirichlet
      Allocation (LDA) automated topic modeling algorithm to the modeling of the
      structure and behavior of virtual organizations found within modern social media
      and social networking environments. As the field of Big Data reveals, an increase
      in the scale of social data available presents new challenges which are not
      tackled by merely scaling up hardware and software. Rather, they necessitate new
      methods and, indeed, new areas of expertise. Natural language processing provides
      one such method. This paper applies LDA to the study of scientific virtual
      organizations whose members employ social technologies. Because of the vast data
      footprint in these virtual platforms, we found that natural language processing
      was needed to 'unlock' and render visible latent, previously unseen
      conversational connections across large textual corpora (spanning profiles,
      discussion threads, forums, and other social media incarnations). We introduce
      variants of LDA and ultimately make the argument that natural language processing
      is a critical interdisciplinary methodology to make better sense of social 'Big
      Data' and we were able to successfully model nested discussion topics from forums
      and blog posts using LDA. Importantly, we found that LDA can move us beyond the
      state-of-the-art in conventional Social Network Analysis techniques. 

PMID- 24930024
TI  - The degree of resistance of erythrocyte membrane cytoskeletal proteins to supra
      physiologic concentrations of calcium: an in vitro study.
AB  - Calcium is a key regulator of cell dynamics. Dysregulation of its cytosolic
      concentration is implicated in the pathophysiology of several diseases. This
      study aimed to assess the effects of calcium on the network of membrane
      cytoskeletal proteins. Erythrocyte membranes were obtained from eight healthy
      donors and incubated with 250 uM and 1.25 mM calcium solutions. Membrane
      cytoskeletal proteins were quantified using SDS-PAGE at baseline and after 3 and
      5 days of incubation. Supra-physiologic concentrations of calcium (1.25 mM)
      induced a significant proteolysis in membrane cytoskeletal proteins, compared
      with magnesium (p < 0.001). Actin exhibited the highest sensitivity to calcium
      induced proteolysis (6.8 +/- 0.3 vs. 5.3 +/- 0.6, p < 0.001), while spectrin
      (39.9 +/- 1.0 vs. 40.3 +/- 2.0, p = 0.393) and band-6 (6.3 +/- 0.3 vs. 6.8 +/-
      0.8, p = 0.191) were more resistant to proteolysis after incubation with calcium
      in the range of endoplasmic reticulum concentrations (250 uM). Aggregation of
      membrane cytoskeletal proteins was determined after centrifugation and was
      significantly higher after incubation with calcium ions compared with control,
      EDTA and magnesium solutions (p < 0.001). In a supra-physiologic range of 1.25-10
      mM of calcium ions, there was a nearly perfect linear relationship between
      calcium concentration and aggregation of erythrocyte membrane cytoskeletal
      proteins (R(2) = 0.971, p < 0.001). Our observation suggests a strong interaction
      between calcium ions and membrane cytoskeletal network. Cumulative effects of
      disrupted calcium homeostasis on cytoskeletal proteins need to be further
      investigated at extended periods of time in disease states.

PMID- 24930025
TI  - Molecular dynamics simulations of a membrane protein/amphipol complex.
AB  - Amphipathic polymers known as "amphipols" provide a highly stabilizing
      environment for handling membrane proteins in aqueous solutions. A8-35, an
      amphipol with a polyacrylate backbone and hydrophobic grafts, has been
      extensively characterized and widely employed for structural and functional
      studies of membrane proteins using biochemical and biophysical approaches. Given
      the sensitivity of membrane proteins to their environment, it is important to
      examine what effects amphipols may have on the structure and dynamics of the
      proteins they complex. Here we present the first molecular dynamics study of an
      amphipol-stabilized membrane protein, using Escherichia coli OmpX as a model. We
      begin by describing the structure of the complexes formed by supplementing OmpX
      with increasing amounts of A8-35, in order to determine how the amphipol
      interacts with the transmembrane and extramembrane surfaces of the protein. We
      then compare the dynamics of the protein in either A8-35, a detergent, or a lipid
      bilayer. We find that protein dynamics on all accessible length scales is
      restrained by A8-35, which provides a basis to understanding some of the
      stabilizing and functional effects of amphipols that have been experimentally
      observed. 

PMID- 24930027
TI  - "The Glasgow effect?"- the result of the geographical patterning of deprived
      areas?
AB  - The aim of this research was to examine whether the excess mortality found in
      Glasgow, compared to other cities in the UK ("Glasgow effect"), could be
      attributed to patterns of the distribution of deprived neighbourhoods within the
      cities. Data on mortality and deprivation at a neighbourhood scale were used to
      examine the impact of the patterning of neighbourhood deprivation on mortality in
      Glasgow, Liverpool and Manchester. Analysis using a combination of GIS and
      statistical approaches, including a Moran's I test and Conditional Auto
      Regressive models to capture residual spatial autocorrelation, was carried out.
      The pattern of deprivation was found to be more dispersed in Glasgow compared to
      the other cities. The impact of surrounding deprivation at two different scales
      shows strong impact on neighbourhood health outcomes in Glasgow and Liverpool but
      not in Manchester, suggesting that patterning is not a major contribution to the
      excess mortality in Glasgow. 

PMID- 24930026
TI  - The Dictyostelium discoideum RACK1 orthologue has roles in growth and
      development.
AB  - BACKGROUND: The receptor for activated C-kinase 1 (RACK1) is a conserved protein
      belonging to the WD40 repeat family of proteins. It folds into a beta propeller
      with seven blades which allow interactions with many proteins. Thus it can serve
      as a scaffolding protein and have roles in several cellular processes. RESULTS:
      We identified the product of the Dictyostelium discoideum gpbB gene as the
      Dictyostelium RACK1 homolog. The protein is mainly cytosolic but can also
      associate with cellular membranes. DdRACK1 binds to phosphoinositides (PIPs) in
      protein-lipid overlay and liposome-binding assays. The basis of this activity
      resides in a basic region located in the extended loop between blades 6 and 7 as
      revealed by mutational analysis. Similar to RACK1 proteins from other organisms
      DdRACK1 interacts with G protein subunits alpha, beta and gamma as shown by yeast
      two-hybrid, pulldown, and immunoprecipitation assays. Unlike the Saccharomyces
      cerevisiae and Cryptococcus neoformans RACK1 proteins it does not appear to take
      over Gbeta function in D. discoideum as developmental and other defects were not
      rescued in Gbeta null mutants overexpressing GFP-DdRACK1. Overexpression of GFP
      tagged DdRACK1 and a mutant version (DdRACK1mut) which carried a charge-reversal
      mutation in the basic region in wild type cells led to changes during growth and
      development. CONCLUSION: DdRACK1 interacts with heterotrimeric G proteins and can
      through these interactions impact on processes specifically regulated by these
      proteins.

PMID- 24930028
TI  - Genotypic and phenotypic spectrum in attenuated variants of Lesch-Nyhan disease.
AB  - Lesch-Nyhan disease and its attenuated variants are caused by deficiency of the
      purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt).
      All patients exhibit excessive production of uric acid, which increases the risk
      for nephrolithiasis, renal failure, gouty arthritis and tophi. The mildest
      phenotype includes only problems related to overproduction of uric acid. The most
      severe clinical phenotype includes prominent neurological abnormalities and the
      universal feature is self-injurious behavior. In between the mildest and most
      severe syndromes is a broad spectrum of phenotypes with varying degrees of
      neurological, neurocognitive and behavioral abnormalities. The effect of HPRT1
      gene mutations on residual HGprt enzyme activity is the most relevant factor
      contributing to disease phenotype. Attenuated clinical phenotypes are associated
      with residual enzyme function, whereas the most severe phenotype is usually
      associated with null activity. In cases of gouty arthritis with urate
      overproduction, a careful evaluation for motor impairments or neurocognitive
      abnormalities may help to identify attenuated variants of Lesch-Nyhan disease for
      better management. 

PMID- 24930029
TI  - A novel de novo mutation of the TITF1/NKX2-1 gene causing ataxia, benign
      hereditary chorea, hypothyroidism and a pituitary mass in a UK family and review
      of the literature.
AB  - Benign hereditary chorea (BHC) is a rare autosomal dominant condition
      characterized by early onset, non-progressive chorea, usually caused by mutations
      in the thyroid transcription factor-1 gene (TITF1). We describe a novel mutation
      arising de novo in a proband presenting in infancy with delayed walking and
      ataxia. She later developed chorea, then hypothyroidism and a large cystic
      pituitary mass. Her daughter presented in infancy with delayed walking and ataxia
      and went on to develop non-progressive chorea and a hormonally inactive cystic
      pituitary mass. Mutational analysis of the whole coding region of the TITF1 gene
      was undertaken and compared with a population study of 160 control subjects. This
      showed that both affected subjects have a heterozygous A > T substitution at
      nucleotide 727 of the TITF1 gene changing lysine to a stop codon at residue 211.
      Genetic analysis of parents and siblings of the proband confirmed that the
      mutation arose de novo in the proband. The mutated lysine is an evolutionarily
      highly conserved amino acid in the protein homoeodomain (HD) where most point
      mutations associated with BHC are located. The range of mutations in BHC is
      reviewed with particular emphasis on pituitary abnormalities. Cystic pituitary
      masses and abnormalities of the sella turcica are reported in just 6.4 % of
      published cases. This is a new nonsense mutation associated with ataxia, benign
      chorea and pituitary abnormalities which further extends the phenotype of this
      condition. Mutational screening of TITF1 is important in cases of sporadic or
      dominant juvenile-onset ataxia, with mild chorea where no other cause is found,
      particularly if pituitary abnormalities are seen on imaging. 

PMID- 24930030
TI  - Focused cerebellar laser light induced hyperthermia improves symptoms and
      pathology of polyglutamine disease SCA1 in a mouse model.
AB  - Spinocerebellar ataxia 1 (SCA1) results from pathologic glutamine expansion in
      the ataxin-1 protein (ATXN1). This misfolded ATXN1 causes severe Purkinje cell
      (PC) loss and cerebellar ataxia in both humans and mice with the SCA1 disease.
      The molecular chaperone heat-shock proteins (HSPs) are known to modulate
      polyglutamine protein aggregation and are neuroprotective. Since HSPs are induced
      under stress, we explored the effects of focused laser light induced hyperthermia
      (HT) on HSP-mediated protection against ATXN1 toxicity. We first tested the
      effects of HT in a cell culture model and found that HT induced Hsp70 and
      increased its localization to nuclear inclusions in HeLa cells expressing GFP
      ATXN1[82Q]. HT treatment decreased ATXN1 aggregation by making GFP-ATXN1[82Q]
      inclusions smaller and more numerous compared to non-treated cells. Further, we
      tested our HT approach in vivo using a transgenic (Tg) mouse model of SCA1. We
      found that our laser method increased cerebellar temperature from 38 to 40 
      degrees C without causing any neuronal damage or inflammatory response.
      Interestingly, mild cerebellar HT stimulated the production of Hsp70 to a
      significant level. Furthermore, multiple exposure of focused cerebellar laser
      light induced HT to heterozygous SCA1 transgenic (Tg) mice significantly
      suppressed the SCA1 phenotype as compared to sham-treated control animals.
      Moreover, in treated SCA1 Tg mice, the levels of PC calcium signaling/buffering
      protein calbindin-D28k markedly increased followed by a reduction in PC
      neurodegenerative morphology. Taken together, our data suggest that laser light
      induced HT is a novel non-invasive approach to treat SCA1 and maybe other
      polyglutamine disorders. 

PMID- 24930031
TI  - Extracellular matrix stiffness and composition jointly regulate the induction of
      malignant phenotypes in mammary epithelium.
AB  - In vitro models of normal mammary epithelium have correlated increased
      extracellular matrix (ECM) stiffness with malignant phenotypes. However, the role
      of increased stiffness in this transformation remains unclear because of
      difficulties in controlling ECM stiffness, composition and architecture
      independently. Here we demonstrate that interpenetrating networks of
      reconstituted basement membrane matrix and alginate can be used to modulate ECM
      stiffness independently of composition and architecture. We find that, in normal
      mammary epithelial cells, increasing ECM stiffness alone induces malignant
      phenotypes but that the effect is completely abrogated when accompanied by an
      increase in basement-membrane ligands. We also find that the combination of
      stiffness and composition is sensed through beta4 integrin, Rac1, and the PI3K
      pathway, and suggest a mechanism in which an increase in ECM stiffness, without
      an increase in basement membrane ligands, prevents normal alpha6beta4 integrin
      clustering into hemidesmosomes. 

PMID- 24930032
TI  - Gradated assembly of multiple proteins into supramolecular nanomaterials.
AB  - Biomaterials exhibiting precise ratios of different bioactive protein components
      are critical for applications ranging from vaccines to regenerative medicine, but
      their design is often hindered by limited choices and cross-reactivity of protein
      conjugation chemistries. Here, we describe a strategy for inducing multiple
      different expressed proteins of choice to assemble into nanofibres and gels with
      exceptional compositional control. The strategy employs 'betaTail' tags, which
      allow for good protein expression in bacteriological cultures, yet can be induced
      to co-assemble into nanomaterials when mixed with additional beta-sheet
      fibrillizing peptides. Multiple different betaTail fusion proteins could be
      inserted into peptide nanofibres alone or in combination at predictable, smoothly
      gradated concentrations, providing a simple yet versatile route to install
      precise combinations of proteins into nanomaterials. The technology is
      illustrated by achieving precisely targeted hues using mixtures of fluorescent
      proteins, by creating nanofibres bearing enzymatic activity, and by adjusting
      antigenic dominance in vaccines. 

PMID- 24930034
TI  - Population pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1
      receptor modulator.
AB  - Ponesimod (ACT-128800), a reversible, orally active, selective S1P1 receptor
      modulator, prevents the egress of lymphocytes from the lymph node into the
      systemic circulation. It is currently in clinical development for the treatment
      of relapsing multiple sclerosis. Modulation of circulating lymphocytes serves as
      biomarker of efficacy and safety, such that the quantitative characterization of
      the pharmacokinetic/pharmacodynamic (PK/PD) relationship guides the clinical
      development of the compound. The availability of a variety of doses, dosing
      regimens, and treatment durations permitted estimation of the pharmacokinetics
      characterized by an absorption lag time followed by a sequential zero/first-order
      absorption and two compartments with first-order elimination. The PD are modeled
      as an indirect-effect model with rates of appearance and disappearance of
      lymphocytes in blood with a circadian rhythm and a drug effect on the rate of
      appearance. The model suggests a circadian variation of 9% and a maximum
      inhibition of 86% of total lymphocyte count with high doses at steady state. It
      was instrumental for the selection of doses for subsequent studies that confirmed
      the effect plateau in total lymphocyte count at approximately 0.5 * 10(9)
      counts/L.

PMID- 24930033
TI  - Management of recurrent stress incontinence following a sling.
AB  - Management of recurrent or persistent stress urinary incontinence (RSI) following
      primary insertion of a synthetic midurethral sling (MUS) remains a challenge for
      the urologist since no consensus is available to favor one treatment over
      another. Complete workup should be carried out, including cystoscopy, urodynamics
      and potentially a pelvic floor ultrasound as a diagnostic adjunct. Various
      surgical options have been described for RSI, apart from another MUS, including
      tightening of or shortening a previously placed MUS, a mini-sling, a salvage
      spiral sling, a colposuspension, the ACT(r) system, an artificial urinary
      sphincter or ultimately a urinary diversion. Treatment depends ultimately on the
      experience and the expertise of the surgeon but it appears most reasonable to
      offer a repeat MUS (retropubic or transobturator), a pubovaginal sling or bulking
      agents to women with RSI. Appropriate counseling of patients to set realistic
      outcomes is key as it may be more practical to aim more for symptomatic
      improvement than cure.

PMID- 24930035
TI  - Antizyme (AZ) regulates intestinal cell growth independent of polyamines.
AB  - Since antizyme (AZ) is known to inhibit cell proliferation and to increase
      apoptosis, the question arises as to whether these effects occur independently of
      polyamines. Intestinal epithelial cells (IEC-6) were grown in control medium and
      medium containing 5 mM difluoromethylornithine (DFMO) to inhibit ODC, DFMO + 5 uM
      spermidine (SPD), DFMO + 5 uM spermine (SPM), or DFMO + 10 uM putrescine (PUT)
      for 4 days and various parameters of growth were measured along with AZ levels.
      Cell counts were significantly decreased and mean doubling times were
      significantly increased by DFMO. Putrescine restored growth in the presence of
      DFMO. However, both SPD and SPM when added with DFMO caused a much greater
      inhibition of growth than did DFMO alone, and both of these polyamines caused a
      dramatic increase in AZ. The addition of SPD or SPM to media containing DFMO +
      PUT significantly inhibited growth and caused a significant increase in AZ. IEC-6
      cells transfected with AZ-siRNA grew more than twice as rapidly as either control
      cells or those incubated with DFMO, indicating that removal of AZ increases
      growth in cells in which polyamine synthesis is inhibited as well as in control
      cells. In a separate experiment, the addition of SPD increased AZ levels and
      inhibited growth of cells incubated with DFMO by 50%. The addition of 10 mM
      asparagine (ASN) prevented the increase in AZ and restored growth to control
      levels. These results show that cell growth in the presence or absence of ODC
      activity and in the presence or absence of polyamines depends only on the levels
      of AZ. Therefore, the effects of AZ on cell growth are independent of polyamines.

PMID- 24930036
TI  - Coverage, compliance and factors associated with utilization of iron
      supplementation during pregnancy in eight rural districts of Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Despite the efforts to reduce iron deficiency during pregnancy,
      information on the coverage and factors associated with utilization of iron
      supplements is lacking. The study is intended to assess the coverage, compliance
      and factors associated with the use of prenatal iron supplements in eight rural
      districts of Ethiopia. METHODS: The study comprised two independent surveys
      conducted among pregnant women (n = 414) and women who gave birth in the
      preceding year of the survey (n = 1573). In both cases, respondents were selected
      using multistage sampling technique and data were collected via structured
      questionnaire. Predictors of iron supplement utilization (ranked categories of
      number of prenatal supplements taken) were identified using ordinal logistic
      regression. The outputs of the analysis are given using adjusted Odds Ratio (OR)
      with 95% Confidence Interval (CI). RESULTS: Among women who gave birth in the
      preceding year, 35.4% (95% CI: 31.3-39.5) were given/prescribed prenatal iron
      supplement during the index pregnancy and only 3.5% were supplemented for the
      recommended 91 or more days. Compared to women who had 4 or more ANC visits,
      those with 0, 1, 2 and 3 visits had 0.04, 0.33, 0.50 and 0.60 times less odds of
      iron supplement utilization, respectively. Women lacking comprehensive knowledge
      of anemia (OR = 0. 75 (95% CI: 0.57-0.97)) and those who weren't informed about
      the importance of iron supplementation during the pregnancy (OR = 0. 05 (95% CI:
      0.04-0.07)) had significantly lower utilization. On the other hand, in pregnant
      women the prevalence of anemia was 33.2%. Among pregnant women who were
      given/prescribed supplements, the average level of compliance was 74.9% and about
      25.1% had less than 70% adherence. The leading reported reasons for non-adherence
      were side-effects (63.3%) and forgetfulness (16.7%). CONCLUSION: Promoting early
      and frequent ANC, enhancing the quality of ANC counseling and promoting the
      knowledge of women on anemia are essential strategies for improving the
      utilization of iron supplements.

PMID- 24930038
TI  - Using human umbilical cord cells for tissue engineering: a comparison with skin
      cells.
AB  - The epithelial cells and Wharton's jelly cells (WJC) from the human umbilical
      cord have yet to be extensively studied in respect to their capacity to generate
      tissue-engineered substitutes for clinical applications. Our reconstruction
      strategy, based on the self-assembly approach of tissue engineering, allows the
      production of various types of living human tissues such as skin and cornea from
      a wide range of cell types originating from post-natal tissue sources. Here we
      placed epithelial cells and WJC from the umbilical cord in the context of a
      reconstructed skin substitute in combination with skin keratinocytes and
      fibroblasts. We compared the ability of the epithelial cells from both sources to
      generate a stratified, differentiated skin-like epithelium upon exposure to air
      when cultured on the two stromal cell types. Conversely, the ability of the WJC
      to behave as dermal fibroblasts, producing extracellular matrix and supporting
      the formation of a differentiated epithelium for both types of epithelial cells,
      was also investigated. Of the four types of constructs produced, the combination
      of WJC and keratinocytes was the most similar to skin engineered from dermal
      fibroblasts and keratinocytes. When cultured on dermal fibroblasts, the cord
      epithelial cells were able to differentiate in vitro into a stratified
      multilayered epithelium expressing molecules characteristic of keratinocyte
      differentiation after exposure to air, and maintaining the expression of keratins
      K18 and K19, typical of the umbilical cord epithelium. WJC were able to support
      the growth and differentiation of keratinocytes, especially at the early stages
      of air-liquid culture. In contrast, cord epithelial cells cultured on WJC did not
      form a differentiated epidermis when exposed to air. These results support the
      premise that the tissue from which cells originate can largely affect the
      properties and homoeostasis of reconstructed substitutes featuring both
      epithelial and stromal compartments. 

PMID- 24930037
TI  - Aberrant gut microbiota composition at the onset of type 1 diabetes in young
      children.
AB  - AIMS/HYPOTHESIS: Recent studies indicate that an aberrant gut microbiota is
      associated with the development of type 1 diabetes, yet little is known about the
      microbiota in children who have diabetes at an early age. To this end, the
      microbiota of children aged 1-5 years with new-onset type 1 diabetes was compared
      with the microbiota of age-matched healthy controls. METHODS: A deep global
      analysis of the gut microbiota composition was established by phylogenetic
      microarray analysis using a Human Intestinal Tract Chip (HITChip). RESULTS:
      Principal component analyses highlighted the importance of age when comparing age
      matched pairs. In pairs younger than 2.9 years, the combined abundance of the
      class Bacilli (notably streptococci) and the phylum Bacteroidetes was higher in
      diabetic children, whereas the combined abundance of members of Clostridium
      clusters IV and XIVa was higher in the healthy controls. Controls older than 2.9
      years were characterised by a higher fraction of butyrate-producing species
      within Clostridium clusters IV and XIVa than was seen in the corresponding
      diabetic children or in children from the younger age groups, while the diabetic
      children older than 2.9 years could be differentiated by having an increased
      microbial diversity. CONCLUSIONS/INTERPRETATION: The results from both age groups
      suggest that non-diabetic children have a more balanced microbiota in which
      butyrate-producing species appear to hold a pivotal position.

PMID- 24930039
TI  - Service evaluation to establish the sensitivity, specificity and additional value
      of broad-range 16S rDNA PCR for the diagnosis of infective endocarditis from
      resected endocardial material in patients from eight UK and Ireland hospitals.
AB  - Infective endocarditis (IE) can be diagnosed in the clinical microbiology
      laboratory by culturing explanted heart valve material. We present a service
      evaluation that examines the sensitivity and specificity of a broad-range 16S
      rDNA polymerase chain reaction (PCR) assay for the detection of the causative
      microbe in culture-proven and culture-negative cases of IE. A clinical case-note
      review was performed for 151 patients, from eight UK and Ireland hospitals, whose
      endocardial specimens were referred to the Microbiology Laboratory at Great
      Ormond Street Hospital (GOSH) for broad-range 16S rDNA PCR over a 12-year period.
      PCR detects the causative microbe in 35/47 cases of culture-proven IE and
      provides an aetiological agent in 43/69 cases of culture-negative IE. The
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of the 16S rDNA PCR assay were calculated for this series of selected
      samples using the clinical diagnosis of IE as the reference standard. The values
      obtained are as follows: sensitivity = 67 %, specificity = 91 %, PPV = 96 % and
      NPV = 46 %. A wide range of organisms are detected by PCR, with Streptococcus
      spp. detected most frequently and a relatively large number of cases of
      Bartonella spp. and Tropheryma whipplei IE. PCR testing of explanted heart valves
      is recommended in addition to culture techniques to increase diagnostic yield.
      The data describing the aetiological agents in a large UK and Ireland series of
      culture-negative IE will allow future development of the diagnostic algorithm to
      include real-time PCR assays targeted at specific organisms.

PMID- 24930041
TI  - Penicillin susceptibility breakpoints for Streptococcus pneumoniae and their
      effect on susceptibility categorisation in Germany (1997-2013).
AB  - Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was
      conducted in Germany. From July 1, 1997, to June 30, 2013, data on penicillin
      susceptibility were available for 20,437 isolates. 2,790 of these isolates (13.7
      %) originate from patients with meningitis and 17,647 isolates (86.3 %) are from
      non-meningitis cases. A slight decline in isolates susceptible at 0.06 and 0.12
      MUg/ml can be noticed over the years. Overall, 89.1 % of the isolates had minimum
      inhibitory concentrations (MICs) of <=0.015 MUg/ml. In 2012/2013, the first three
      isolates of Streptococcus pneumoniae with MICs of 8 MUg/ml were found. The
      application of different guidelines with other MIC breakpoints for the
      interpretation of penicillin resistance leads to differences in susceptibility
      categorisation. According to the pre-2008 Clinical and Laboratory Standards
      Institute (CLSI) interpretive criteria, 5.3 % of isolates overall were
      intermediate and 1.4 % were resistant to penicillin. Application of the 2008-2014
      CLSI interpretive criteria resulted in 7.6 % resistance among meningitis cases
      and 0.5 % intermediate resistance in non-meningitis cases. Referring to the 2009
      2014 European Committee on Antimicrobial Susceptibility Testing (EUCAST)
      breakpoints, 7.6 % of the isolates in the meningitis group were resistant to
      penicillin. In the non-meningitis group, 6.1 % of the isolates were intermediate
      and 0.5 % were resistant. These differences should be kept in mind when
      surveillance studies on pneumococcal penicillin resistance are compared.

PMID- 24930040
TI  - Evidence of a clonal expansion of Streptococcus pneumoniae serotype 19A in adults
      as in children assessed by the DiversiLab(r) system.
AB  - Streptococcus pneumoniae serotype 19A was the main serotype responsible for
      invasive pneumococcal disease (IPD) in the Paris area in 2007 and 2009 in both
      adults and children. To verify if a particular clone is emerging, we determined
      the populational structure of S. pneumoniae isolates. Eighty-four S. pneumoniae
      strains responsible for invasive infections isolated from 52 adults and 32
      children hospitalized in Parisian hospitals were analyzed. Capsular typing was
      performed by polymerase chain reaction (PCR) using the semi-automated repetitive
      sequence-based (rep-PCR) DiversiLab(r) System. Multilocus sequence typing (MLST)
      was also performed on 26 strains (ten selected strains after cluster analysis and
      16 control strains). In 2007 and 2009, S. pneumoniae serotype 19A represented,
      respectively, 28.6 % and 25 % of the serotypes involved in IPDs in children and
      13 % and 13.7 % in adults. The rep-PCR DiversiLab(r) analysis showed that the 84
      S. pneumoniae serotype 19A isolates were distributed in five clusters and four
      unique rep-PCR types. Overall, 77/84 (91.6 %) S. pneumoniae 19A serotypes grouped
      into three main genetically related clusters (71/77 belonged to the cluster I).
      The five other strains exhibited different profiles. Using MLST, we demonstrated
      that most strains of the main cluster belonged to clonal complex (CC) 230,
      sequence type (ST) 276. However, for the other strains, the DiversiLab(r) method
      cannot be used to predict to which ST a strain belongs. The DiversiLab(r) method
      allowed us to identify the clonal expansion of S. pneumoniae serotype 19A strains
      isolated from both children and adults in 2007 and 2009.

PMID- 24930042
TI  - Trends in the susceptibility of commonly encountered clinically significant
      anaerobes and susceptibilities of blood isolates of anaerobes to 16 antimicrobial
      agents, including fidaxomicin and rifaximin, 2008-2012, northern Taiwan.
AB  - We investigated the antimicrobial resistance trends and profiles of clinical
      anaerobic isolates in northern Taiwan. Trends in the susceptibility of five
      commonly encountered clinical anaerobic isolates to seven agents from 2008 to
      2012 were measured using the Cochran-Armitage trend test. The minimum inhibitory
      concentrations (MICs) of 16 antimicrobial agents, including fidaxomicin and
      rifaximin, against anaerobic blood isolates from two medical centers were
      determined using the agar dilution method. During the study period,
      susceptibility data on 11,105 isolates were evaluated. Metronidazole and
      chloramphenicol retained excellent activities. Around 20-30 % of isolates of
      Bacteroides and Prevotella species were resistant to ampicillin-sulbactam,
      cefmetazole, flomoxef, and clindamycin. Of the 507 tested blood isolates, the
      rates of resistance to commonly used agents were much higher, namely, 16.2 % for
      amoxicillin-clavulanate, 15.6 % for ampicillin-sulbactam, 24.7 % for cefmetazole,
      and 36.1 % for clindamycin. Notably, 13.5 % of B. fragilis isolates were
      resistant to ertapenem. Also, 15.2 % of B. uniformis, 17.2 % of other Bacteroides
      species, 14.3 % of Prevotella species, and 14 % of Clostridium other than C.
      perfringens isolates were resistant to moxifloxacin. Cefoperazone-sulbactam was
      active against most isolates, except for Clostridium species other than
      perfringens (resistance rate, 18.6 %). Fidaxomicin exerted poor activities
      against most anaerobes tested (MIC90 of >128 MUg/ml for B. fragilis and all
      isolates), except for C. perfringens (MIC90 of 0.03 MUg/ml) and
      Peptostreptococcus micros (MIC90 of 2 MUg/ml). However, rifaximin showed a wide
      range of susceptibilities against the tested anaerobes (MIC90 of 0.5 MUg/ml for
      B. fragilis). The emergence of resistance to ertapenem and moxifloxacin among
      bacteremic anaerobes highlights the need for continuous monitoring.

PMID- 24930043
TI  - Comparison between transthoracic and transesophageal echocardiography in
      screening for infective endocarditis in patients with Staphylococcus aureus
      bacteremia.
AB  - Echocardiography is an important diagnostic tool in evaluating a patient with
      Staphylococcus aureus bacteremia (SAB) for diagnosing infective endocarditis
      (IE). We sought to compare the utility of transthoracic echocardiography (TTE)
      with transesophageal echocardiography (TEE) in screening for IE in patients with
      SAB. We performed a retrospective chart review of 285 adult patients from two
      tertiary care hospitals with at least one positive blood culture for S. aureus
      between 2010 and 2012. Patients who underwent echocardiography were divided into
      two groups: TTE (screened with TTE only) and TEE (screened with both TTE and
      TEE). The demographic factors and clinical outcomes were compared between the
      groups. Of the 285 charts reviewed, 213 (74.7 %) patients were screened with
      echocardiography: 183 (85.9 %) were screened with TTE alone and 30 (14.1 %) were
      screened with both TTE and TEE. TEE disclosed more cases of definite IE than TTE
      (8 [26.7 %] vs. 22 [12.0 %], p = 0.046). The TEE group had higher mortality than
      the TTE group (15 [50.0 %] vs. 43 [23.5 %], p = 0.004). In patients with definite
      IE, mortality was higher in the TEE group than in the TTE group (6 [75.0 %] vs. 6
      [27.3 %], p = 0.034). TEE discovered additional findings that were missed by TTE
      in 36.7 % of cases and refuted the findings of TTE in 13.3 % of cases. We do not
      support the routine use of TEE in patients with uncomplicated SAB. High-risk
      patients in which IE is a serious consideration should undergo investigation with
      TEE.

PMID- 24930044
TI  - Fractalkine levels are elevated early after PCI-treated ST-elevation myocardial
      infarction; no influence of autologous bone marrow derived stem cell injection.
AB  - BACKGROUND: Fractalkine (CX3CL1) is a chemokine associated with atherosclerosis
      and inflammation. There is limited knowledge of fractalkine levels during acute
      myocardial infarction (AMI) and stem cell treatment. We aimed to investigate the
      time profile of circulating fractalkine and gene expression of its receptor
      CX3CR1 during AMI, and the influence of intracoronary autologous bone marrow stem
      cell (mBMC) transplantation (given 6 days after AMI) on fractalkine levels.
      METHODS: We examined fractalkine levels at different time points by enzyme-linked
      immunosorbent assay (ELISA) in 20 patients with AMI, and 10 patients with stable
      angina pectoris (AP) undergoing percutaneous coronary intervention (PCI), and in
      100 patients included in the randomized Autologous Stem-Cell Transplantation in
      Acute Myocardial Infarction (ASTAMI) trial. RESULTS: Patients with AMI had
      significantly elevated levels 3- and 12 h after PCI compared to patients with
      stable AP. After 12 h levels were similar in the two groups. An inverse pattern
      was observed in gene expression levels. No correlation between fractalkine levels
      and myocardial injury or infarct size was seen. We could not demonstrate any
      influence of autologous mBMC transplantation on fractalkine levels. CONCLUSION:
      Fractalkine levels are elevated the first 12 h after PCI in patients with AMI,
      however, not correlated to infarct size. The inverse pattern in gene expression
      of fractalkine receptor (CX3CR1) might be a compensatory mechanism. No effect of
      autologous mBMC transplantation given 6 days after AMI on fractalkine levels was
      observed.

PMID- 24930046
TI  - How is the Beads Task related to intolerance of uncertainty in anxiety disorders?
AB  - Intolerance of uncertainty (IU) is a cognitive bias associated with anxiety
      disorders that has only been reliably measured using self-report instruments. The
      current study investigated relationships between a probabilistic inference task -
      the Beads Task - and self-report IU. Individuals with anxiety disorders (ANX) and
      non-anxious controls (NAC) completed self-report measures as well as the Beads
      Task at three levels of difficulty. The Beads Task successfully induced task
      related uncertainty as the decision became more difficult. While the two groups
      did not differ on the observable performance related measures, the ANX group was
      significantly more distressed during the task than were the NACs. Moreover, among
      the ANX group, self-reported IU was correlated with draws to decision and
      distress during the task. The Beads Task appears to provoke distress associated
      with uncertainty for anxious individuals, rather than altering their behavioral
      responses; thus, clinical implications and avenues for future research are
      discussed. 

PMID- 24930047
TI  - The neural basis of attentional control in visual search.
AB  - How do we localise and identify target objects among distractors in visual
      scenes? The role of selective attention in visual search has been studied for
      decades and the outlines of a general processing model are now beginning to
      emerge. Attentional processes unfold in real time and this review describes four
      temporally and functionally dissociable stages of attention in visual search
      (preparation, guidance, selection, and identification). Insights from
      neuroscientific studies of visual attention suggest that our ability to find
      target objects in visual search is based on processes that operate at each of
      these four stages, in close association with working memory and recurrent
      feedback mechanisms. 

PMID- 24930045
TI  - Inhibition of glutathione peroxidase mediates the collateral sensitivity of
      multidrug-resistant cells to tiopronin.
AB  - Multidrug resistance (MDR) is a major obstacle to the successful chemotherapy of
      cancer. MDR is often the result of overexpression of ATP-binding cassette
      transporters following chemotherapy. A common ATP-binding cassette transporter
      that is overexpressed in MDR cancer cells is P-glycoprotein, which actively
      effluxes drugs against a concentration gradient, producing an MDR phenotype.
      Collateral sensitivity (CS), a phenomenon of drug hypersensitivity, is defined as
      the ability of certain compounds to selectively target MDR cells, but not the
      drug-sensitive parent cells from which they were derived. The drug tiopronin has
      been previously shown to elicit CS. However, unlike other CS agents, the
      mechanism of action was not dependent on the expression of P-glycoprotein in MDR
      cells. We have determined that the CS activity of tiopronin is mediated by the
      generation of reactive oxygen species (ROS) and that CS can be reversed by a
      variety of ROS-scavenging compounds. Specifically, selective toxicity of
      tiopronin toward MDR cells is achieved by inhibition of glutathione peroxidase
      (GPx), and the mode of inhibition of GPx1 by tiopronin is shown in this report.
      Why MDR cells are particularly sensitive to ROS is discussed, as is the
      difficulty in exploiting this hypersensitivity to tiopronin in the clinic. 

PMID- 24930048
TI  - Positive posttraumatic stress disorder screens among first-time medical cannabis
      patients: prevalence and association with other substance use.
AB  - Twenty-one states and the District of Columbia have passed legislation allowing
      for the use of medical cannabis for those individuals with qualifying medical
      conditions, which include posttraumatic stress disorder (PTSD) for a growing
      number of states. Little information is available regarding PTSD among medical
      cannabis patients. This study seeks to provide initial data on this topic by
      examining the prevalence and correlates of positive PTSD screens among a sample
      of patients seeking medical cannabis certification for the first time (n=186).
      Twenty-three percent (42/186; 95% confidence interval [CI] =17%-29%) of the
      patients in the study sample screened positive for PTSD. Moreover, the group that
      screened positive for PTSD had higher percentages of lifetime prescription
      opioid, cocaine, prescription sedative, and street opioid use, as well as a
      higher percentage of recent prescription sedative use, than the group that
      screened negative for PTSD. These findings highlight the relatively common use of
      other substances among medical cannabis patients with significant PTSD symptoms,
      even when compared with other patients seeking medical cannabis for the first
      time. As a growing number of states include PTSD among the list of qualifying
      medical conditions for medical cannabis, additional research is needed to better
      characterize the longitudinal relationship between medical cannabis use and PTSD
      symptoms. 

PMID- 24930049
TI  - A new method of cannabis ingestion: the dangers of dabs?
AB  - A new method for administering cannabinoids, called butane hash oil ("dabs"), is
      gaining popularity among marijuana users. Despite press reports that suggest that
      "dabbing" is riskier than smoking flower cannabis, no data address whether dabs
      users experience more problems from use than those who prefer flower cannabis.
      OBJECTIVE: The present study aimed to gather preliminary information on dabs
      users and test whether dabs use is associated with more problems than using
      flower cannabis. METHOD: Participants (n=357) reported on their history of
      cannabis use, their experience with hash oil and the process of "dabbing,"
      reasons for choosing "dabs" over other methods, and any problems related to both
      flower cannabis and butane hash oil. RESULTS: Analyses revealed that using "dabs"
      created no more problems or accidents than using flower cannabis. Participants
      did report that "dabs" led to higher tolerance and withdrawal (as defined by the
      participants), suggesting that the practice might be more likely to lead to
      symptoms of addiction or dependence. CONCLUSIONS: The use of butane hash oil has
      spread outside of the medical marijuana community, and users view it as
      significantly more dangerous than other forms of cannabis use.

PMID- 24930050
TI  - Predictors of the initiation and persistence of internet addiction among
      adolescents in Taiwan.
AB  - PURPOSE: The present study examined the psychosocial factors associated with the
      initiation and persistence of Internet addiction among adolescents in Taiwan.
      METHODS: A total of 2315 students from 26 high schools were assessed in the 10th
      grade, with follow-up performed in the 11th grade, in Taipei, Taiwan. Self
      administered questionnaires were collected in each year to assess the pattern of
      changes in Internet addiction and psychosocial factors. RESULTS: Of the 1602
      students without an Internet addiction in the 10th grade, 253 (15.8%) had
      initiated Internet addiction by grade 11. Multivariate analysis results indicated
      that greater engagement in online activities (i.e., social network website use,
      online gaming), depression, and lower school bonding in grade 10 coupled with an
      increase in online activities, depression, and smoking from grades 10 to 11
      predicted the initiation of Internet addiction. Of the 605 students with Internet
      addiction in the 10th grade, the addiction had persisted for 383 students (63.3%)
      in grade 11. An increase in the existence of depression and alcohol use from
      grades 10 to 11 predicted the persistence of Internet addiction. CONCLUSIONS:
      Online activities, depression, and substance use were important predictors of
      youth initiation and of the persistence of Internet addiction.

PMID- 24930052
TI  - The influence of protective and risk factors in individual, peer and school
      domains on Thai adolescents' alcohol and illicit drug use: a survey.
AB  - This study investigates risk and protective factors for substance abuse in a
      sample of 1778 students attending technical colleges in Bangkok and Nakhon
      Ratchasima provinces of Thailand using a self-report questionnaire modified from
      the Communities That Care youth survey. Low school commitment was strongly
      associated with illicit drug use, with adjusted odds ratios ranging from 2.84
      (glue sniffing) to 10.06 (ecstasy). Having friends using drugs, and friends with
      delinquent behaviors increased the risk of using alcohol and illegal drugs, with
      adjusted odds ratios of 6.84 and 6.72 respectively for marijuana use. For
      protective factors, approximately 40-60% of students with high levels of moral
      belief, participation in religious activities, and social skills were less likely
      to use alcohol. It is concluded that peer influence is a significant contributor
      to Thai adolescents' participation in substance abuse and that engaging in
      religiosity may assist adolescents to internalize negative aspects of harmful
      drugs into positive perceptions and encourage them to avoid alcohol and illegal
      drugs. 

PMID- 24930051
TI  - Beliefs and attitudes regarding drug treatment: application of the theory of
      planned behavior in African-American cocaine users.
AB  - BACKGROUND: The Theory of Planned Behavior (TPB) can provide insights into
      perceived need for cocaine treatment among African American cocaine users.
      METHODS: A cross-sectional community sample of 400 (50% rural) not-in-treatment
      African-American cocaine users was identified through respondent-driven sampling
      in one urban and two rural counties in Arkansas. Measures included self-reports
      of attitudes and beliefs about cocaine treatment, perceived need and perceived
      effectiveness of treatment, and positive and negative cocaine expectancies.
      Normative beliefs were measured by perceived stigma and consequences of stigma
      regarding drug use and drug treatment. Perceived control was measured by
      readiness for treatment, prior drug treatment, and perceived ability to cut down
      on cocaine use without treatment. FINDINGS: Multiple regression analysis found
      that older age (standardized regression coefficient beta=0.15, P<0.001), rural
      residence (beta=-0.09, P=0.025), effectiveness of treatment (beta=0.39, P<0.001),
      negative cocaine expectancies (beta=0.138, P=0.003), experiences of rejection
      (beta=0.18, P<0.001), need for secrecy (beta=0.12, P=0.002), and readiness for
      treatment (beta=0.15, P<0.001) were independently associated with perceived need
      for cocaine treatment. CONCLUSIONS: TPB is a relevant model for understanding
      perceived need for treatment among African-American cocaine users. Research has
      shown perceived need to be a major correlate of treatment participation. Study
      results should be applicable for designing interventions to encourage treatment
      participation.

PMID- 24930054
TI  - Ecology, evolution and control of plant viruses and their vectors.

PMID- 24930055
TI  - Penetrating facial injury with an "Airsoft" pellet: a case report.
AB  - Airsoft is a recreational combat sport that originated in Japan in the 1970s and
      is currently increasing in popularity in the UK. Participants use air or
      electrically powered weapons to fire small plastic pellets at a controlled
      pressure. UK law strictly regulates the maximum muzzle velocity and the type of
      ammunition used in these weapons. A search of published papers found several
      reports of penetrating ocular injuries caused by Airsoft pellets, but no reports
      of penetrating injuries to other areas of the body. We report the case of a 25
      year-old man who sustained a penetrating injury to the cheek after being shot
      with an Airsoft weapon. 

PMID- 24930053
TI  - Differential use of other tobacco products among current and former cigarette
      smokers by income level.
AB  - With the declining sales of cigarettes, the tobacco industry has been promoting
      other forms of combustible and smokeless tobacco to current and former cigarette
      smokers. Exposure to the promotion of tobacco products has been shown to vary by
      income level. We combined the 2006 through 2011 National Surveys on Drug Use and
      Health to compare the prevalence and patterns of other tobacco use (cigar, snuff,
      and chewing tobacco) between current and former cigarette smokers by income
      level. Other tobacco use was minimal among females and among male non-smokers.
      Approximately a third of both current and former male cigarette smokers reported
      past-year other tobacco use. Overall, current smokers were more likely than
      former smokers to have used cigars (adjusted odds ratio (AOR) 1.69, 95% CI 1.50
      1.92) or snuff (AOR 1.14, 95% CI 1.01-1.28) in the past year. The association of
      smoking status with other tobacco use differed by income level (interaction term
      p-value<0.001). Among lower income groups, current smokers were more likely to
      use cigars and snuff compared to former smokers. Among the highest income group,
      former smokers were just as likely to use smokeless tobacco as current smokers.
      The differing patterns of use of other tobacco between current and former smokers
      by income level highlight a need for studies to understand the motivations for
      the use of these products and their role in smoking cessation. 

PMID- 24930056
TI  - Unusual cause of iatrogenic anterior open bite after bilateral sagittal split
      mandibular advancement osteotomy.
AB  - We describe a case of anterior open bite after bilateral sagittal split
      mandibular advancement osteotomy. The discrepancy in height between the proximal
      and distal segments at the osteotomy sites damaged the soft tissue and caused
      bony interferences. Removal of the maxillary third molars and bilateral removal
      of bony interferences of the distal segments using a bur led to full resolution
      and a good orthognathic outcome on follow-up. 

PMID- 24930057
TI  - Accuracy and reliability of linear measurements using 3-dimensional computed
      tomographic imaging software for Le Fort I osteotomy: common mistakes.

PMID- 24930058
TI  - Frontline treatment with gemcitabine, oxaliplatin and erlotinib for the treatment
      of advanced or metastatic pancreatic cancer: a multicenter phase II study of the
      Hellenic Oncology Research Group (HORG).
AB  - PURPOSE: Intravenous gemcitabine is the standard of care for patients with
      metastatic cancer of the pancreas. Gemcitabine-based chemotherapy combinations,
      either doublets or triplets, have been tested in the past but have offered a
      small advantage (Brodoefel et al. in Eur J Radiol 73:594-600, 2010). In the
      present study, we present the results of the triplet gemcitabine-oxaliplatin
      erlotinib combination as firstline treatment in this setting. PATIENTS AND
      METHODS: Seventy-one eligible patients were included in this study. All patients
      received chemotherapy with gemcitabine (1,100 mg/m(2) on days 1 and 8) plus
      oxaliplatin (130 mg/m(2) on day 8) and erlotinib (100 mg p.o./day for 21 days).
      The treatment cycle was 21 days. RESULTS: Partial response was achieved in 15
      patients (21%; 95% CI 11.63-30.62) and stable disease in 15 patients (21%). Forty
      one patients (57.8%) experienced disease progression. Median progression-free
      survival was 5.2 months (range 0.6-34.7; 95% CI 3.71-6.76). The median overall
      survival was 10.5 months (95% CI 7.39-13.61) and the 1-year survival estimate
      47.3%. The main adverse events were grade 3/4 anemia occurring in three (4.2%)
      patients and grade 3 and 4 thrombocytopenia occurring in eight (11.3%) and three
      (4.2%) patients, respectively. Grade 4 neutropenia was rare (1.4%), and one
      patient presented febrile neutropenia. CONCLUSION: This study demonstrated that
      the combination of gemcitabine, oxaliplatin and erlotinib is active, well
      tolerated and safe for patients with metastatic adenocarcinoma of the pancreas.
      However, the results do not seem to be better than those reported with
      chemotherapy alone.

PMID- 24930059
TI  - Risk estimation of multiple recurrence and progression of non muscle invasive
      bladder carcinoma using new mathematical models.
AB  - OBJECTIVE: To apply new mathematical models according to Non Muscle Invasive
      Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate
      risk estimation of multiple recurrences and tumor progression. The classical Cox
      model is not valid for the assessment of this kind of events becausethe time
      betweenrecurrencesin the same patientmay be stronglycorrelated. These new models
      for risk estimation of recurrence/progression lead to individualized monitoring
      and treatment plan. MATERIALS AND METHODS: 960 patients with primary NMIBC were
      enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were
      validated in 240 patients from other center. Transurethral resection of the
      bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant
      localized chemotherapy was performed. The variables analyzed were: number and
      tumor size, age, chemotherapy and histopathology. The endpoints were time to
      recurrence and time to progression. Cox model and its extensions were used as
      joint frailty model for multiple recurrence and progression. Model accuracy was
      calculated using Harrell's concordance index (c-index). RESULTS: 468 (48.8%)
      patients developed at least one tumor recurrence and tumor progression was
      reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age,
      grade, number, size, treatment and the number of prior recurrences. All these
      together with age, stage and grade are the variables for progression risk.
      Concordance index was 0.64 and 0.85 for multiple recurrence and progression
      respectively. CONCLUSION: the high concordance reported besides to the validation
      process in external source, allow accurate multi-recurrence/progression risk
      estimation. As consequence, it is possible to schedule a follow-up and treatment
      individualized plan in new and recurrent NMCB cases.

PMID- 24930060
TI  - Diabetes and cancer: 5 years into the recent controversy.
AB  - Diabetes and cancer are common chronic disorders. The literature has long
      recognised that type 2 diabetes (T2D) is associated with an increased incident
      risk of several cancer types, independent of the mutual risk factor, obesity.
      However, in June 2009, four papers were published simultaneously in Diabetologia,
      the official journal of the European Association for the Study of Diabetes,
      raising questions of a link between diabetes therapies, notably the long-acting
      insulin analogue, glargine, and increased cancer risk. These papers awakened an
      unprecedented debate in the diabetes community, drawing in cancer experts and
      bringing together representatives from these two large, traditionally non
      intersecting, biomedical communities. This Current Perspective summarises the
      events that followed the 'breaking news' from summer 2009: the pitfalls
      encountered; the increased mutual understanding between diabetes and cancer
      researchers; and the direction of current research. Much of the debate on the
      clinical impact of this controversy has been played out in the diabetes
      literature: here, we update the oncology readership. 

PMID- 24930061
TI  - Synthesis of hyaluronic acid oligosaccharides and exploration of a fluorous
      assisted approach.
AB  - The synthesis of hyaluronic acid oligomers (tri- and tetrasaccharide) is
      described. We have followed a pre-glycosylation oxidation strategy. Glucuronic
      acid units were directly employed in coupling reactions with suitably protected
      glucosamine derivatives. In order to simplify the purification of synthetic
      intermediates, a fluorous-assisted strategy has been also explored. Using this
      approach, a hyaluronic acid trisaccharide was prepared. 

PMID- 24930070
TI  - Exaggerated exercise blood pressure response and risk of stroke in patients
      referred for stress testing.
AB  - BACKGROUND/OBJECTIVES: There is some evidence to suggest that exercise systolic
      blood pressure (SBP) may be associated with future risk of stroke in subjects
      without a history of coronary artery disease (CAD). However, the value of an
      exaggerated exercise SBP response (EESBPR) for predicting stroke in patients
      referred for stress testing for clinical reasons has not been investigated.
      METHODS: We evaluated a community-based sample of 10,047 patients with known or
      suspected CAD who underwent treadmill exercise echocardiography. An EESBPR was
      defined as a peak exercise SBP of >220mmHg. The ratio of the increase in SBP
      during exercise to exercise workload (DeltaSBPeEW) was also estimated. The
      endpoints were stroke of any type, ischemic stroke and hemorrhagic stroke. Median
      follow-up was 3.5years. RESULTS: Annualized rates of stroke of any type, ischemic
      stroke and hemorrhagic stroke were 0.6% (95% CI 0.53-0.67), 0.49% (95% CI 0.42
      0.56) and 0.12% (95% CI 0.09-0.15) in patients without EESBPR vs. 0.69% (95% CI
      0.37-1), 0.49% (95% CI 0.23-0.76) and 0.19% (95% CI 0.02-0.35) in those with
      EESBPR (p=0.68, 0.90 and 0.39, respectively). Similarly, there was no significant
      univariate association between DeltaSBPeEW and the occurrence of any endpoint. In
      multivariate analysis, hypertension, male sex, age, diabetes mellitus and resting
      SBP remained predictors of stroke of any type. EESBPR and DeltaSBPeEW were not
      predictors of any of the endpoints evaluated. CONCLUSION: We did not observe any
      significant association between exercise SBP and the future occurrence of stroke
      in patients with known or suspected CAD referred for exercise echocardiography.

PMID- 24930071
TI  - Unexpected inverse relationship between impaired glucose metabolism and
      lipoprotein-associated phospholipase A2 activity in patients with stable vascular
      disease.
AB  - BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity (aLp-PLA2)
      is associated with increased risk of cardiovascular events. In patients with
      stable atherovascular disease, we aimed to investigate whether impaired glucose
      metabolism might be associated with higher risk of elevated aLp-PLA2. METHODS: We
      conducted a cross-sectional study in 825 stable patients after acute coronary
      syndrome, coronary revascularization or after first ischemic stroke (Czech part
      of EUROASPIRE III surveys). We measured aLp-PLA2 using diaDexus commercial kit.
      RESULTS: In multiple step-wise regression analysis, the aLp-PLA2 was
      significantly positively associated with male gender, current smoking, LDL
      cholesterol and metabolic syndrome and negatively with statin treatment, body
      mass index and LDL/apoB ratio. After adjustment for these confounders, we
      observed an inverse relationship between aLp-PLA2 and fasting glycemia [beta
      coefficient -2.18 (p<0.0001)] or glycated hemoglobin A1c (HbA1c) [beta
      coefficient -5.89 (p<0.0001)]. Moreover, we found a positive association between
      aLp-PLA2 and pancreatic beta cell function [beta coefficient +0.10 (p<0.0001)],
      but not with an insulin sensitivity. CONCLUSION: In present study, we cannot
      confirm any additive risk of impaired glucose metabolism in terms of increased
      activity of Lp-PLA2. On the contrary, presence of inadequately controlled
      diabetes mellitus was independently associated with lower risk of elevated aLp
      PLA2 .

PMID- 24930072
TI  - Synthesis and anti-tumor activity evaluation of Matijin-Su derivatives.
AB  - A series of Matijin-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l
      phenylalanol) derivatives was synthesized and evaluated for their anti-tumor
      activities in hepatocellular carcinoma cells. The IC50 of compounds 1, 3, 4, 11,
      13 were less than 20MUM, and compound 1 and 3 showed an IC50 value of less than
      9MUM. Expansion inhibition could be found significantly in compound 1 and 3
      treated human hepatoma cell HepG2 and PLC/PRF/5, while both compounds exhibit
      lower toxicity to human hepatocyte cell line L-02. Compound 1 and 3 could induce
      cell cycle arrest at G1/S phase. This may be attributed to increase level of
      intracellular reactive oxygen species (ROS). Up-regulation of p38 MAPK activity
      in responding the ROS stabilize p53 and activate p21 transcription, the critical
      regulatory in G1/S checkpoint. Observations in this study shed light on the
      potential of MTS derivatives compound 1 and 3 as novel suppressors to human liver
      cancer. 

PMID- 24930073
TI  - Incidence and predictors of exertional hyperthermia after a 15-km road race in
      cool environmental conditions.
AB  - OBJECTIVES: Current knowledge about the incidence and risk factors for exertional
      hyperthermia (core body temperature >=40 degrees C) is predominantly based on
      military populations or small-sized studies in athletes. We assessed the
      incidence of exertional hyperthermia in 227 participants of a 15-km running race,
      and identified predictors for exertional hyperthermia. DESIGN: Observational
      study. METHODS: We measured intestinal core body temperature before and
      immediately after the race. To identify predictive factors of maximum core body
      temperature, we entered sex, age, BMI, post-finish dehydration, number of
      training weeks, fluid intake before and during the race, finish time, and core
      body temperature change during warming-up into a backward linear regression
      analysis. Additionally, two subgroups of hyperthermic and non-hyperthermic
      participants were compared. RESULTS: In a WBGT of 11 degrees C, core body
      temperature increased from 37.6+/-0.4 degrees C at baseline to 37.8+/-0.4 degrees
      C after warming-up, and 39.2+/-0.7 degrees C at the finish. A total of 15% of all
      participants had exertional hyperthermia at the finish. Age, BMI, fluid intake
      before the race and the core body temperature change during warming-up
      significantly predicted maximal core body temperature (p<0.001). Participants
      with hyperthermia at the finish line had a significantly greater core body
      temperature rise (p<0.01) during the warming-up compared to non-hyperthermic
      peers, but similar race times (p=0.46). CONCLUSIONS: 15% of the recreational
      runners developed exertional hyperthermia, whilst core body temperature change
      during the warming-up was identified as strongest predictor for core body
      temperature at the finish. This study emphasizes that exertional hyperthermia is
      a common phenomenon in recreational athletes, and can be partially predicted.

PMID- 24930075
TI  - [Acute cardiac insufficiency. Do we finally have an opportunity to improve the
      prognosis?].

PMID- 24930074
TI  - The inter and intra rater reliability of the Netball Movement Screening Tool.
AB  - OBJECTIVES: To establish the inter- and intra-rater reliability of the Netball
      Movement Screening Tool, for screening adolescent female netball players. DESIGN:
      Inter- and intra-rater reliability study. METHODS: Forty secondary school netball
      players were recruited to take part in the study. Twenty subjects were screened
      simultaneously and independently by two raters to ascertain inter-rater
      agreement. Twenty subjects were scored by rater one on two occasions, separated
      by a week, to ascertain intra-rater agreement. Inter and intra-rater agreement
      was assessed utilising the two-way mixed inter class correlation coefficient and
      weighted kappa statistics. RESULTS: No significant demographic differences were
      found between the inter and intra-rater groups of subjects. Inter class
      correlation coefficients' demonstrated excellent inter-rater (two-way mixed inter
      class correlation coefficients 0.84, standard error of measurement 0.25) and
      intra-rater (two-way mixed inter class correlation coefficients 0.96, standard
      error of measurement 0.13) reliability for the overall Netball Movement Screening
      Tool score and substantial-excellent (two-way mixed inter class correlation
      coefficients 1.0-0.65) inter-rater and substantial-excellent intra-rater (two-way
      mixed inter class correlation coefficients 0.96-0.79) reliability for the
      component scores of the Netball Movement Screening Tool. Kappa statistic showed
      substantial to poor inter-rater (k=0.75-0.32) and intra-rater (k=0.77-0.27)
      agreement for individual tests of the NMST. CONCLUSIONS: The Netball Movement
      Screening Tool may be a reliable screening tool for adolescent netball players;
      however the individual test scores have low reliability. The screening tool can
      be administered reliably by raters with similar levels of training in the tool
      but variable clinical experience. On-going research needs to be undertaken to
      ascertain whether the Netball Movement Screening Tool is a valid tool in
      ascertaining increased injury risk for netball players.

PMID- 24930076
TI  - [Epidemiology of acute heart failure].
AB  - In Spain, as in all other developed countries, heart failure is a colossal
      healthcare challenge. It is estimated that more than 1,300,000 people have heart
      failure in Spain. Each year, there are more than 100,000 hospital admissions for
      this process and the numbers are progressively increasing. Approximately 2% of
      emergency visits are related to this condition. Nearly 50% of inpatients are
      older than 75 years and have multiple comorbidities. Readmissions are common.
      Mortality at 1 year is around 16% after discharge but is close to 60% at 10
      years. The associated annual overall costs are around 2,500 million euros. Every
      year more than 17,000 people die from heart failure, which is the fourth most
      frequent cause of death in Spain. Mortality rates have been reduced but, because
      of more advanced age at admission and the associated multiple comorbidities, in
      hospital mortality has remained largely unchanged during the last 12 years and is
      nearly 10%. De novo heart failure causes greater morbidity and mortality and
      consequently there is a need for early identification and treatment. Strategies
      to coordinate healthcare levels and develop effective preventive programs are
      needed to tackle this formidable problem. 

PMID- 24930077
TI  - [Acute heart failure: precipitating factors and prevention].
AB  - Acute heart failure episodes, whether onset or decompensation of a chronic form,
      are most often precipitated by a concurrent process or disease, described as
      precipitating factors of heart failure. In this article, we review these
      precipitating factors, their proportions and clinical relevance in general and in
      subgroups of patients, their relationship with prognosis, and their possible
      prevention. 

PMID- 24930078
TI  - [Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].
AB  - Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms
      of presentation of acute heart failure. Both entities are serious, with high
      mortality, and require early diagnosis and prompt and aggressive management.
      Acute pulmonary edema is due to the passage of fluid through the
      alveolarcapillary membrane and is usually the result of an acute cardiac episode.
      Correct evaluation and clinical identification of the process is essential in the
      management of acute pulmonary edema. The initial aim of treatment is to ensure
      hemodynamic stability and to correct hypoxemia. Other measures that can be used
      are vasodilators such as nitroglycerin, loop diuretics and, in specific
      instances, opioids. Cardiogenic shock is characterized by sustained
      hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index <
      2.2l/min/m(2). The process typically presents with hypotension (systolic blood
      pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent
      or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular
      failure due to acute myocardial infarction. Treatment consists of general
      measures to reverse acidosis and hypoxemia, as well as the use of vasopressors
      and inotropic drugs. Early coronary revascularization has been demonstrated to
      improve survival in shock associated with ischaemic heart disease.

PMID- 24930079
TI  - [Diagnosis of acute heart failure and relevance of biomarkers in elderly
      patients].
AB  - Diagnosis of acute heart failure (HF) is difficult in elderly patients with
      multiple comorbidities. Risk scales and classification criteria based exclusively
      on clinical manifestations, such as the Framingham scales, lack sufficient
      specificity. In addition to clinical manifestations, diagnosis should be based on
      two key factors: natriuretic peptides and echocardiographic study. When there is
      clinical suspicion of acute HF, a normal natriuretic peptide level will rule out
      this process. When a consistent clinical suspicion is present, an
      echocardiographic study should also be performed. Diagnosis of HF with preserved
      ejection fraction (HF/pEF) requires detection of an enlarged left atrium or the
      presence of parameters of diastolic dysfunction. Elevation of cardiac biomarkers
      seems to be due to myocardial injury and the compensatory mechanisms of the body
      against this injury (hormone and inflammatory response and repair mechanisms).
      Elevation of markers of cardiac damage (troponins and natriuretic peptides) have
      been shown to be useful both in the diagnosis of acute HF and in prediction of
      outcome. MMP-2 could be useful in the diagnosis of HF/pEF. In addition to
      biomarkers with diagnostic value, other biomarkers are helpful in prognosis in
      the acute phase of HF, such as biomarkers of renal failure (eGFR, cystatin and
      urea), inflammation (cytokines and CRP), and the cell regeneration marker,
      galectin-3. A promising idea that is under investigation is the use of panels of
      biomarkers, which could allow more accurate diagnosis and prognosis of acute HF. 

PMID- 24930080
TI  - [Organ damage and cardiorenal syndrome in acute heart failure].
AB  - Heart failure is a complex syndrome that affects almost all organs and systems of
      the body. Signs and symptoms of organ dysfunction, in particular kidney
      dysfunction, may be accentuated or become evident for the first time during acute
      decompensation of heart failure. Cardiorenal syndrome has been defined as the
      simultaneous dysfunction of both the heart and the kidney, regardless of which of
      the two organs may have suffered the initial damage and regardless also of their
      previous functional status. Research into the mechanisms regulating the complex
      relationship between the two organs is prompting the search for new biomarkers to
      help physicians detect renal damage in subclinical stages. Hence, a preventive
      approach to renal dysfunction may be adopted in the clinical setting in the near
      future. This article provides a general overview of cardiorenal syndrome and an
      update of the physiopathological mechanisms involved. Special emphasis is placed
      on the role of visceral congestion as an emergent mechanism in this syndrome. 

PMID- 24930081
TI  - [Possibilities of clinical echocardiography in patients with heart failure: some
      examples from clinical practice].
AB  - Clinical echocardiography is a fast, non-invasive and safe diagnostic method
      carried out at the patient's bedside by clinicians, not necessarily
      cardiologists, and can provide useful information about cardiac anatomy, with
      estimates of volumes, diameters, the presence or absence pericardial effusion,
      and visualization of ventricular wall motion and valve function. The most
      practical measure of ventricular function to distinguish between patients with
      systolic dysfunction and those with preserved systolic function is ejection
      fraction, which can be estimated approximately. The new small pocket
      echocardiography devices that have become available in recent years offer major
      advantages in terms of availability and their cost can be considered accessible
      compared with that of other devices. An undisputed practical advantage is their
      portability and ease of use. Clinical echocardiography is perfectly compatible
      with the subsequent performance of echocardiography by a highly qualified expert.

PMID- 24930082
TI  - [Diuretic therapy in acute heart failure].
AB  - Diuretics are widely recommended in patients with acute heart failure (AHF).
      Unfortunately, despite their widespread use, limited data are available from
      randomized clinical trials to guide clinicians on the appropriate management of
      diuretic therapy. Loop diuretics are considered the first-line diuretic therapy,
      especially intravenous furosemide, but the best mode of administration (high-dose
      versus low-dose and continuous infusion versus bolus) is unclear. When diuretic
      resistance develops, different therapeutic strategies can be adopted, including
      combined diuretic therapy with thiazide diuretics and/or aldosterone antagonists.
      Low or "non-diuretic" doses (25-50mg QD) of aldosterone antagonists have been
      demonstrated to confer a survival benefit in patients with heart failure and
      reduced ejection fraction and consequently should be prescribed in all such
      patients, unless contraindicated by potassium and/or renal function values. There
      is less evidence on the use of aldosterone antagonists at higher or "diuretic"
      doses (>= 100mg QD) but these drugs could be useful in relieving congestive
      symptoms in combination with furosemide. Thiazide diuretics can also be helpful
      as they have synergic effects with loop diuretics by inhibiting sodium
      reabsorption in distal parts of the nephron. The effect of diuretic therapy in
      AHF should be monitored with careful observation of clinical signs and symptoms
      of congestion. Serum electrolytes and kidney function should also be monitored
      during the use of intravenous diuretics. 

PMID- 24930083
TI  - [Alternatives to conventional diuretic therapy in heart failure].
AB  - Although treatment of acute heart failure is based primarily on the
      administration of intravenous loop diuretics, evidence supporting this practice
      is still scarce and there is uncertainty about the optimal dose. The existence of
      a considerable percentage of patients refractory to diuretic therapy and
      worsening of renal failure associated with the use of these drugs, with possible
      implications for medium-term mortality, have prompted the search for more
      effective and safer alternatives. Extracorporeal purification techniques, such as
      ultrafiltration, have demonstrated efficacy, although their superiority is
      unclear, due to the possible adverse effects associated with the procedure. The
      use of low-dose dopamine is not superior to conventional diuretic therapy after
      the first few hours of treatment. Moreover, combination with furosemide and
      hypertonic saline could be a valid alternative for patients with refractory
      congestion and depressed ejection fraction and serum creatinine <= 2.5mg/dL, but
      further studies are needed before its widespread use. The use of tolvaptan may be
      an effective alternative in the short-term but its use may be limited by its
      price. There is still controversy about whether treatment with loop diuretics is
      associated with higher mortality in all groups of patients with HF exacerbations.
      These controversies should be clarified by future clinical trials. 

PMID- 24930084
TI  - [Vasoactive and inotropic drugs in acute heart failure].
AB  - Vasoactive and inotropic drugs provide effective symptomatic and hemodynamic
      relief in the short term but can increase mortality in the long-term.
      Consequently, their use should be restricted to the indications described in
      clinical practice guidelines. The present article reviews the main drugs and the
      available evidence on their use. 

PMID- 24930085
TI  - [Non-invasive mechanical ventilation in the treatment of acute heart failure].
AB  - When acute heart failure progresses and there is acute cardiogenic pulmonary
      edema, routine therapeutic measures should be accompanied by other measures that
      help to correct oxygenation of the patient. The final and most drastic step is
      mechanical ventilation. Non-invasive ventilation has been developed in the last
      few years as a method that attempts to improve oxygenation without the need for
      intubation, thus, in theory, reducing morbidity and mortality in these patients.
      The present article describes the controversies surrounding the results of this
      technique and discusses its indications. The article also discusses how to start
      non-invasive ventilation in patients with acute pulmonary edema from a practical
      point of view. 

PMID- 24930086
TI  - [Complementary treatment of acute heart failure in patients with diabetes,
      chronic obstructive pulmonary disease or anemia].
AB  - Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are
      comorbidities with a high prevalence and impact in heart failure (HF). The
      presence of these comorbidities considerably worsens the prognosis of HF.
      Diabetic patients have a higher likelihood of developing symptoms of HF and both
      the treatment of diabetes and that of acute HF are altered by the coexistence of
      both entities. The glycemic targets in patients with acute HF are not well
      defined, but could show a U-shaped relationship. Stress hyperglycemia in non
      diabetic patients with HF could also have a deleterious effect on the medium-term
      prognosis. The inter-relationship between COPD and HF hampers diagnosis due to
      the overlap between the symptoms and signs of both entities and complementary
      investigations. The treatment of acute HF is also altered by the presence of
      COPD. Anemia is highly prevalent and is often the direct cause of decompensated
      HF, the most common cause being iron deficiency anemia. Iron replacement therapy,
      specifically intravenous forms, has helped to improve the prognosis of acute HF. 

PMID- 24930087
TI  - [Organ-protection therapy. A new therapeutic approach for acute heart failure?].
AB  - Unlike the prolonged benefit produced by the treatment of chronic heart failure,
      newer drugs tested for the treatment of acute heart failure in the last decade
      have failed to provide evidence of clinical benefit beyond some improvement in
      symptom relief. In particular, no drug has shown the ability to reduce the higher
      medium- and long-term risk of morbidity and mortality in these patients after an
      episode of decompensation. Current understanding of the pathophysiology of acute
      heart failure and its consequences has led to the hypothesis that, beyond symptom
      control, effective therapies for this syndrome should target not only the
      hemodynamic changes of the initial phase of the syndrome but should also
      "protect" the organism from the activation of neurohumoral and inflammatory
      pathways triggered by the decompensation episode, which persist in time and
      confer a risk of deleterious effects in several organs and tissues. Serelaxin, a
      new drug related to the peptidic endogenous hormones of the relaxin family, has
      recently been shown to provide multiple beneficial effects in terms of "organ
      protection" - not only in the cardiovascular and renal systems - from these acute
      heart failure-related deleterious changes. This drug has already been tested in
      acute heart failure patients with encouraging results in terms of medium-term
      clinical benefit, rendering serelaxin as a serious candidate for first-line,
      prognosis-modifying therapy in this syndrome. 

PMID- 24930088
TI  - PEGylated rhFGF-2 conveys long-term neuroprotection and improves neuronal
      function in a rat model of Parkinson's disease.
AB  - Fibroblast growth factor 2 (FGF-2) has a neurotrophic effect on dopaminergic
      neurons in vitro and in vivo, and exhibits beneficial effects in animal models of
      neurodegenerative disorders such as Parkinson's disease (PD). The poor stability
      and short half-life of FGF-2, however, have hampered its clinical use for
      neurological diseases. In the present study, we modified native recombinant human
      FGF-2 (rhFGF-2) by covalently attaching polyethylene glycol (PEG) polymers, named
      PEGylation, to enhance its neuroprotection efficacy in 6-hydroxydopamine (6-OHDA)
      induced model of PD. In vitro, PEG-rhFGF-2 performed better biostability in 6
      OHDA-induced PC-12 cells than native rhFGF-2. The in vivo data showed that,
      compared with native rhFGF-2, PEGylated rhFGF-2 was more efficacious in
      preventing 6-OHDA-induced lesion upon tyrosine hydroxylase-positive neurons in
      the substantia nigra (SN), improving the apomorphine-induced rotational behavior
      and the 6-OHDA-induced decline in tissue concentration of dopamine (DA) and its
      metabolites. Importantly, our data showed that the superior pharmacological
      activity of PEGylated rhFGF-2 is probably due to its greater permeability through
      the blood-brain barrier and better in vivo stability compared to native rhFGF-2.
      The enhanced stability and bioavailability of PEGylated rhFGF-2 make this
      molecule a great therapeutic candidate for neurodegenerative diseases such as PD
      and mood disorders.

PMID- 24930089
TI  - Sexual disorders in women with MS: assessment and management.
AB  - OBJECTIVES: Summarize the data on sexual disorders in women with multiple
      sclerosis (MS). METHOD: Review of 99 Pubmed articles covering sexual dysfunction
      in women with MS. RESULTS: Prevalence of dysfunction in women with MS varies from
      34% to 85%. They include poor vaginal lubrication, poor clitoral erection, and
      anorgasmia, which correlate with level of disability. Specific brain stem and
      pyramidal lesions appear to correlate with anorgasmia. Age and duration of the
      disease correlate with sexual disorders, but not age at onset. Secondary
      consequences of MS, including bladder and bowel dysfunction, spasticity, pain,
      fatigue, depression, anxiety, and side effects of medication contribute to sexual
      dysfunction. Treatments can involve alpha-blockers or phosphodiesterase-5
      inhibitors to increase smooth muscle relaxation, while lubricants and oestrogen
      therapy can help vaginal dryness, burning and dyspareunia. Antidepressants can
      delay (or abolish) orgasm, suggesting reducing dosage or combining them with PDE5
      inhibitors. Counselling should emphasize planning sexual activities, reducing
      fatigue, managing positions, preventing incontinence, promoting sexual aids,
      extra-genital and other sexual options to achieve pleasurable and intimacy.
      Psychosocial interventions should include couples' relationship and communication
      skills to increase satisfaction. CONCLUSION: Sexual dysfunctions in women with MS
      are amenable to treatments covering primary, secondary and tertiary consequences
      of the disease.

PMID- 24930090
TI  - Home care, need for increased physician involvement in the 21st century.

PMID- 24930091
TI  - My moral compass and ethical decision making in public health.

PMID- 24930094
TI  - Muscular tubes of urethra engineered from adipose-derived stem cells and
      polyglycolic acid mesh in a bioreactor.
AB  - We have explored the feasibility of using adipose-derived stem cells (ADSCs) and
      polyglycolic acid (PGA) for constructing muscular tubes of urethra in a
      bioreactor. With the induction of by 5-azacytidine, ADSCs were found to acquire a
      myoblast phenotype. Here we seeded ADSCs in a PGA mesh to construct the cell-PGA
      complex that was cultured statically for 1 week. Afterwards, the cell-PGA complex
      was subjected to extension stimulation in a bioreactor for 5 weeks. A muscular
      tube of urethra was formed after 6 weeks. Histological examination showed
      differentiated ADSCs and collagenous fibers had orientated well. This study
      demonstrates that tissue engineering of urethra tissues in vitro by using a
      bioreactor leads to tissue maturation and the differentiation of ADSCs. This
      novel technique could provide an effective approach for urethra tissue
      engineering. 

PMID- 24930093
TI  - BMP2 cross-linked by transglutaminase 2 to collagen-plla scaffold promotes
      osteogenic differentiation in mesenchymal stem cells.
AB  - Transglutaminase 2 (TG2) was used to attach biologically-active BMP2 to collagen
      type I-coated poly-L-lactic acid (PLLA) nanofibrous scaffolds. Irreversibly cross
      linked BMP2 retained its activity and induced Smad-dependent gene expression in
      cells seeded on PLLA-BMP2 scaffolds. These modified scaffolds promote osteogenic
      differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs)
      cultured in low-serum and growth factor free medium and support deposition of the
      calcified matrix and induction of the molecular osteogenic markers Runx2,
      osteopontin, osteonectin and bone sialoprotein. Importantly, the PLLA-BMP2
      scaffolds did not support chondrogenic differentiation in hBMSCs as there was no
      expression of chondrogenic markers aggrecan, Sox 9, and collagen type II, and no
      deposition of cartilaginous glycosaminoglycan-rich matrix. Thus, TG2-mediated
      cross-linking of BMP2 to a scaffold is a novel approach to induce osteoblast
      specific programming of hBMSCs in a spatially controlled manner. 

PMID- 24930092
TI  - Genetic diversity and differentiation of the rhesus macaque (Macaca mulatta)
      population in western Sichuan, China, based on the second exon of the major
      histocompatibility complex class II DQB (MhcMamu-DQB1) alleles.
AB  - BACKGROUND: Rhesus macaques living in western Sichuan, China, have been separated
      into several isolated populations due to habitat fragmentation. Previous studies
      based on the neutral or nearly neutral markers (mitochondrial DNA or
      microsatellites) showed high levels of genetic diversity and moderate genetic
      differentiation in the Sichuan rhesus macaques. Variation at the major
      histocompatibility complex (MHC) loci is widely accepted as being maintained by
      balancing selection, even with a low level of neutral variability in some
      species. However, in small and isolated or bottlenecked populations, balancing
      selection may be overwhelmed by genetic drift. To estimate microevolutionary
      forces acting on the isolated rhesus macaque populations, we examined genetic
      variation at Mhc-DQB1 loci in 119 wild rhesus macaques from five geographically
      isolated populations in western Sichuan, China, and compared the levels of MHC
      variation and differentiation among populations with that previously observed at
      neutral microsatellite markers. RESULTS: 23 Mamu-DQB1 alleles were identified in
      119 rhesus macaques in western Sichuan, China. These macaques exhibited
      relatively high levels of genetic diversity at Mamu-DQB1. The Hanyuan population
      presented the highest genetic variation, whereas the Heishui population was the
      lowest. Analysis of molecular variance (AMOVA) and pairwise FST values showed
      moderate genetic differentiation occurring among the five populations at the Mhc
      DQB1 locus. Non-synonymous substitutions occurred at a higher frequency than
      synonymous substitutions in the peptide binding region. Levels of MHC variation
      within rhesus macaque populations are concordant with microsatellite variation.
      On the phylogenetic tree for the rhesus and crab-eating macaques, extensive
      allele or allelic lineage sharing is observed between the two species.
      CONCLUSIONS: Phylogenetic analyses confirm the apparent trans-species model of
      evolution of the Mhc-DQB1 genes in these macaques. Balancing selection plays an
      important role in sharing allelic lineages between species, but genetic drift may
      share balancing selection dominance to maintain MHC diversity. Great divergence
      at neutral or adaptive markers showed that moderate genetic differentiation had
      occurred in rhesus macaque populations in western Sichuan, China, due to the
      habitat fragmentation caused by long-term geographic barriers and human activity.
      The Heishui population should be paid more attention for its lowest level of
      genetic diversity and relatively great divergence from others.

PMID- 24930096
TI  - Remediation of the effect of adding cyanides on an algal/bacterial treatment of a
      mixture of organic pollutants in a continuous photobioreactor.
AB  - The effect of inorganic pollutants on the treatment of organic pollutants using
      algal/bacterial microcosm was investigated in a continuous photobioreactor. The
      microcosm was composed of Chlorella vulgaris MM1 and Pseudomonas MT1 and was able
      to efficiently treat artificial waste-water contaminated with 6.4 salicylate and
      2.2 mM phenol at a hydraulic retention time of 4 days. No negative effect was
      recorded when the waste-water was supplemented with 1.6 mM thiocyanate; however,
      the treatment efficiency severely deteriorated when the system was challenged
      with 0.74 mM cyanide. Addition of 2 g NaHCO3 l(-1) did not improve the efficiency
      of the treatment. Toxicity of the pollutants to the alga was cyanide >
      thiocyanate > phenol > salicylate. The high toxicity of the waste-water was
      eliminated either by a 25-fold dilution or by photocatalytic pre-treatment which
      allowed the subsequent efficient biological treatment. 

PMID- 24930095
TI  - Ultrasensitive immuno-detection using viral nanoparticles with modular assembly
      using genetically-directed biotinylation.
AB  - We report a novel, modular approach to immuno-detection based on antibody
      recognition and PCR read-out that employs antibody-conjugated bacteriophage and
      easily-manipulated non-pathogenic viruses as affinity agents. Our platform
      employs phage genetically tagged for in vivo biotinylation during phage
      maturation that can easily be linked, through avidin, to any biotinylated
      affinity agent, including full-length antibodies, peptides, lectins or aptamers.
      The presence of analyte is reported with high sensitivity through real-time PCR.
      This approach avoids the need to clone antibody-encoding DNA fragments, allows
      the use of full-length, high affinity antibodies and, by having DNA reporters
      naturally encapsulated inside the bacteriophage, greatly reduces nonspecific
      binding of DNA. We validate the efficacy of this new approach through the
      detection of Vascular Endothelial Growth Factor, a known angiogenic cancer
      biomarker protein, at attomolar concentrations in bronchoalveolar lavage fluid. 

PMID- 24930097
TI  - The operating performance of a biotrickling filter with Lysinibacillus fusiformis
      for the removal of high-loading gaseous chlorobenzene.
AB  - Removal of gaseous chlorobenzene (CB) by a biotrickling filter (BTF) filled with
      modified ceramics and multi-surface hollow balls during gas-liquid mass transfer
      at the steady state was by microbial degradation rather than dissolution in the
      spray liquid or emission into the atmosphere. The BTF was flexible and resistant
      to the acid environment of the spray liquid, with the caveat that the spray
      liquid should be replaced once every 6-7 days. The BTF, loaded with
      Lysinibacillus fusiformis, performed well for purification of high-loading CB
      gas. The maximum CB gas inlet loading rate, 103 g m(-3) h(-1), CB elimination
      capacity, 97 g m(-3) h(-1), and CB removal efficiency, 97.7 %, were reached at a
      spray liquid flow rate of 27.6 ml min(-1), an initial CB concentration of up to
      1,300 mg m(-3), and an empty bed retention time of more than 45 s.

PMID- 24930098
TI  - Characterization and expression of glucosamine-6-phosphate synthase from
      Saccharomyces cerevisiae in Pichia pastoris.
AB  - Glucosamine-6-phosphate (GlcN-6-P) synthase from Saccharomyces cerevisiae was
      expressed in Pichia pastoris SMD1168 GIVING maximum activity of 96 U ml(-1) for
      the enzyme in the culture medium. By SDS-PAGE, the enzyme, a glycosylated
      protein, had an apparent molecular mass of 90 kDa. The enzyme was purified by gel
      exclusion chromatography to near homogeneity, with a 90 % yield and its
      properties were characterized. Optimal activities were at pH 5.5 and 55  degrees
      C, respectively, at which the highest specific activity was 6.8 U mg protein (
      1). The enzyme was stable from pH 4.5 to 5.5 and from 45 to 60  degrees C. The Km
      and Vmax of the GlcN-6-P synthase towards D-fructose 6-phosphate were 2.8 mM and
      6.9 MUmol min(-1) mg(-1), respectively.

PMID- 24930099
TI  - Distance effect of matrix attachment regions on transgene expression in stably
      transfected Chinese hamster ovary cells.
AB  - The beta-globin matrix attachment regions (MARs) were inserted into the 5'-site
      of the eukaryotic expression vector cassette and DNA fragments 350 and 750 bp in
      length were inserted into the site to generate expression vectors with varying
      distances between the expression cassette and MAR. The vectors containing MARs
      increased chloramphenicol acetyltransferase (CAT) expression levels compared to
      the negative control vector lacking the MAR; the highest expression increase was
      3.8-fold. A greater MAR-transgene distance (750 bp) correlated with a greater
      increase in transgene expression when compared to the control vector that lacked
      separation between the MAR and transgene. CAT gene copy numbers were higher in
      cells transformed with the vector possessing a smaller MAR-transgene distance
      (350 bp) than in cells belonging to the other three groups. However, MAR-induced
      transgene expression levels did not exhibit a direct relationship with gene copy
      number.

PMID- 24930100
TI  - High pH (and not free ammonia) is responsible for Anammox inhibition in mildly
      alkaline solutions with excess of ammonium.
AB  - Ammonium is a substrate of the anaerobic ammonium oxidation (Anammox) process but
      it has been suggested as a substrate-inhibitor because of the action of its
      unionized form, free ammonia. High pH of the medium is also an important limiting
      factor of the Anammox bacteria. Both effects are difficult to discriminate. In
      this work the inhibitory effects of high pH, total ammonia (TA) and NH3 on the
      Anammox process were investigated simultaneously. Results confirmed that TA
      caused no inhibition and high pH is a much more important inhibiting factor than
      NH3 in mildly alkaline conditions, based on a multi-factorial analysis. Values of
      pH higher than 7.6 caused Anammox inhibition >10 % and should be avoided during
      the application of the Anammox process in practice.

PMID- 24930101
TI  - Commercial materials as cathode for hydrogen production in microbial electrolysis
      cell.
AB  - The use of commercial electrodes as cathodes in a single-chamber microbial
      electrolysis cell has been investigated. The cell was operated in sequencing
      batch mode and the performance of the electrodes was compared with carbon cloth
      containing 0.5 mg Pt cm(-2). Overall H2 recovery [Formula: see text] was 66.7 +/-
      1.4, 58.7 +/- 1.1 and 55.5 +/- 1.5 % for Pt/CC, Ni and Ti mesh electrodes,
      respectively. Columbic efficiencies of the three cathodes were in the same range
      (74.8 +/- 1.5, 77.6 +/- 1.7 and 75.7 +/- 1.2 % for Pt/CC, Ni and Ti mesh
      electrodes, respectively). A similar performance for the three cathodes under
      near-neutral pH and ambient temperature was obtained. The commercial electrodes
      are much cheaper than carbon cloth containing Pt. Low cost and good performance
      of these electrodes suggest they are suitable cathode materials for large scale
      application.

PMID- 24930102
TI  - Degradation of polyphosphates by polyphosphate kinases from Ruegeria pomeroyi.
AB  - Polyphosphate kinases 2 (PPK2) are key enzymes for polyphosphate utilisation in
      bacteria. The genome of Ruegeria pomeroyi, a marine alpha-proteobacterium,
      includes three Pseudomonas aeruginosa PPK2 homologs. We expressed these homologs
      in Escherichia coli as soluble proteins, purified the protein products and
      compared their metal, pH and nucleotide preferences. The optimal pH was 8.0 for
      SPO1727 and 9.0 for SPO1256. The SPO0224 gene product had two pH optima at eight
      and ten. The SPO0224 protein showed little dependence on metal presence, while
      SPO1256 required Mg(2+). SPO1727 required Mg(2+) but accepted other ions as well.

PMID- 24930103
TI  - Efficient extracellular production of type I secretion pathway-dependent
      Pseudomonas fluorescens lipase in recombinant Escherichia coli by heterologous
      ABC protein exporters.
AB  - Heterologous ABC protein exporters, the apparatus of type I secretion pathway in
      Gram-negative bacteria, were used for extracellular production of Pseudomonas
      fluorescens lipase (TliA) in recombinant Escherichia coli. The effect of the
      expression of different ABC protein exporter gene clusters (P. fluorescens
      tliDEF, Pseudomonas aeruginosa aprDEF, Erwinia chrysanthemi prtDEF, and Serratia
      marcescens lipBCD genes) was examined on the secretion of TliA at growth
      temperatures of 20, 25, 30 and 35  degrees C. TliA secretion in recombinant E.
      coli XL10-Gold varied depending upon type of ABC protein exporter and culture
      temperature. E. coli expressing S. marcescens lipBCD genes showed the highest
      secretion level of TliA (122.8 U ml(-1)) when cultured at 25  degrees C. Thus,
      optimized culture conditions for efficient extracellular production of lipase in
      recombinant E. coli can be designed by changing the type of ABC protein exporter
      and the growth temperature.

PMID- 24930104
TI  - An ice nucleation protein from Fusarium acuminatum: cloning, expression,
      biochemical characterization and computational modeling.
AB  - Ice nucleation proteins (INP) are a major cause of frost damage in plants and
      crops. Here, an INP gene from Fusarium acuminatum was optimized, synthesized,
      expressed in E.coli and subsequently purified and characterized. The protein
      belongs to the second class of ice nucleation proteins with an optimum pH 5.5,
      relative activity and stability between pH 5 and 9.5 and up to 45  degrees C. The
      protein was fully active and stable in the presence of dimethyl sulfoxide (DMSO),
      dioxane, acetone and ethyl acetate. Moreover, it retained over 50 % of its
      original activity in the presence of polyvinyl alcohol. The 3D structure model of
      the INP-F indicated the protein had three distinct domains as exist in other ice
      nucleation proteins with some variations. Considering these promising results,
      INP-F could be a novel candidate for industrial applications.

PMID- 24930105
TI  - Direct patterning of poly(acrylic acid) on polymer surfaces by ion beam
      lithography for the controlled adhesion of mammalian cells.
AB  - Poly(acrylic acid) (PAA)-patterned polystyrene (PS) substrates were prepared by
      ion beam lithography to control cell behaviors of mouse fibroblasts and human
      embryonic kidney cells. Thin PAA films spin-coated on non-biological PS
      substrates were selectively irradiated with energetic proton ions through a
      pattern mask. The irradiated substrates were developed with deionized water to
      generate negative-type PAA patterns. The surface characteristics of the resulting
      PAA-patterned PS surface, such as surface morphology, chemical structure and
      composition and wettability, were investigated. Well-defined 100 MUm PAA patterns
      were effectively formed on relatively hydrophobic PS substrates by ion beam
      lithography at higher fluences than 5 * 10(14) ions/cm(2). Moreover, based on the
      in vitro cell culture test, cells were adhered and proliferated favorably onto
      hydrophilic PAA regions separated by hydrophobic PS regions on the PAA-patterned
      PS substrates, and thereby leading to the formation of well-defined cell
      patterns.

PMID- 24930106
TI  - A simple method for construction of artificial microRNA vector in plant.
AB  - Artificial microRNA (amiRNA) is a powerful tool for silencing genes in many plant
      species. Here we provide an easy method to construct amiRNA vectors that
      reinvents the Golden Gate cloning approach and features a novel system called top
      speed amiRNA construction (TAC). This speedy approach accomplishes one
      restriction-ligation step in only 5 min, allowing easy and high-throughput vector
      construction. Three primers were annealed to be a specific adaptor, then digested
      and ligated on our novel vector pTAC. Importantly, this method allows the
      recombined amiRNA constructs to maintain the precursor of osa-miR528 with
      exception of the desired amiRNA/amiRNA* sequences. Using this method, our results
      showed the expected decrease of targeted genes in Nicotiana benthamiana and Oryza
      sativa.

PMID- 24930107
TI  - Enhanced phytate dephosphorylation by using Candida melibiosica yeast-based
      biofuel cell.
AB  - We report for the first time that Candida melibiosica expresses enhanced phytase
      activity when grown under biofuel cell polarization in a nutrient-poor medium,
      containing only fructose as a carbohydrate source. Phytase activity during the
      cultivation under polarization reached up to 25 U per g dry biomass, exceeding
      with 20 +/- 3 % those of the control. A participation of the enzyme in the
      adaptation processes to the stress conditions is proposed. In addition, steady
      state electrical outputs were achieved during biofuel cell operation at
      continuous polarization under constant load. The obtained results show that C.
      melibiosica yeast-based biofuel cell could be used for simultaneous electricity
      generation and phytate bioremediation.

PMID- 24930108
TI  - Genomic imprinting analysis of Igf2/H19 in porcine cloned fetuses using
      parthenogenetic somatic cells as nuclear donors.
AB  - To gain insight into parthenogenesis in pigs, we report for the first time that
      using parthenogenetic somatic cells as nuclear donors (PSCNT), the porcine
      parthenogenetic fetus can develop to gestational day 39. Weight and morphological
      analysis revealed that PSCNT fetuses were smaller and developmentally retarded
      when compared to normally fertilized controls. Quantitative gene expression
      analysis indicated that in PSCNT fetuses, H19 was over-expressed, whereas Igf2
      was significantly reduced (p < 0.05) compared with their controls. In addition,
      bisulfite-sequencing PCR results demonstrated that H19 differentially DNA
      methylated regions (DMRs) were hypomethylated in PSCNT fetuses, while Igf2 DMRs
      were hypermethylated in both PSCNT and control fetuses. Our results suggest that
      extended development of the porcine parthenogenetic fetus can be accomplished
      using PSCNT and that abnormal DNA methylation of H19 DMRs might contribute to the
      critical barrier of parthenogenesis in pigs.

PMID- 24930109
TI  - Method for the stabilization and immobilization of enzymatic extracts and its
      application to the decolorization of textile dyes.
AB  - Peroxidases from Pleurotus eryngii have been investigated for their ability to
      degrade recalcitrant, phenolic pollutants. The use of crude enzymatic extracts
      can reduce the high costs associated with enzyme purification, and enzyme
      immobilization can enhance enzyme stability and recovery. The present study tests
      the effectiveness of various conditions for crude enzyme stabilization in
      polyethylene glycol and glycine solutions, and immobilization on monofunctional
      and heterofunctional agarose solid supports. Glycine at 0.5 M at 4  degrees C and
      pH 4 was most effective stabilization agent for the crude enzymatic extracts, and
      enzyme immobilization efficiency was greatest for heterofunctional supports. MANA
      glyoxyl heterofunctional supports were demonstrated to have the greatest
      enhancement of decolorization (1.3-fold) and velocity of substrate consumption
      (fivefold). Therefore, the application of crude enzymatic extracts to industrial
      processes, such as dye decolorization, represents a cost-effective alternative to
      purified enzymes.

PMID- 24930110
TI  - Deletion of a KU80 homolog enhances homologous recombination in the
      thermotolerant yeast Kluyveromyces marxianus.
AB  - Targeted gene replacement in the thermotolerant yeast Kluyveromyces marxianus
      KCTC 17555 has been hampered by its propensity to non-homologous end joining
      (NHEJ). To enhance homologous recombination (HR) by blocking NHEJ, we identified
      and disrupted the K. marxianus KU80 gene. The ku80 deletion mutant strain
      (Kmku80?) of K. marxianus KCTC 17555 did not show apparent growth defects under
      several conditions with the exception of exposure to tunicamycin. The targeted
      disruption of the three model genes, KmLEU2, KmPDC1, and KmPDC5, was increased by
      13-70 % in Kmku80?, although the efficiency was greatly affected by the length of
      the homologous flanking fragments. In contrast, the double HR frequency was 0
      13.7 % in the wild-type strain even with flanking fragments 1 kb long. Therefore,
      Kmku80? promises to be a useful recipient strain for targeted gene manipulation.

PMID- 24930111
TI  - Optimal subset selection of primary sequence features using the genetic algorithm
      for thermophilic proteins identification.
AB  - A genetic algorithm (GA) coupled with multiple linear regression (MLR) was used
      to extract useful features from amino acids and g-gap dipeptides for
      distinguishing between thermophilic and non-thermophilic proteins. The method was
      trained by a benchmark dataset of 915 thermophilic and 793 non-thermophilic
      proteins. The method reached an overall accuracy of 95.4 % in a Jackknife test
      using nine amino acids, 38 0-gap dipeptides and 29 1-gap dipeptides. The accuracy
      as a function of protein size ranged between 85.8 and 96.9 %. The overall
      accuracies of three independent tests were 93, 93.4 and 91.8 %. The observed
      results of detecting thermophilic proteins suggest that the GA-MLR approach
      described herein should be a powerful method for selecting features that describe
      thermostabile machines and be an aid in the design of more stable proteins.

PMID- 24930112
TI  - Biosynthesis of pinene from glucose using metabolically-engineered
      Corynebacterium glutamicum.
AB  - Pinene is a monoterpenes (C10) that is produced in a genetically-engineered
      microbial host for its industrial applications in fragrances, flavoring agents,
      pharmaceuticals, and biofuels. Herein, we have metabolically-engineered
      Corynebacterium glutamicum, to produce pinene and studied its toxicity in C.
      glutamicum. Geranyl diphosphate synthases (GPPS) and pinene synthases (PS),
      obtained from Pinus taeda and Abies grandis, were co-expressed with over
      expressed native 1-deoxy-d-xylulose-5-phosphate synthase (Dxs) and isopentenyl
      diphosphate isomerase (Idi) from C. glutamicum using CoryneBrick vector. Most
      strains expressing PS-GPPSs produced detectable amounts of pinene, but co
      expression of DXS and IDI with PS (P. taeda) and GPPS (A. grandis) resulted in 27
      MUg +/- 7 alpha-pinene g(-1) cell dry weight, which is the first report in C.
      glutamicum. Further engineering of PS and GPPS in the C. glutamicum strain may
      increase pinene production.

PMID- 24930113
TI  - Ectopic expression of reprogramming factors enhances the development of cloned
      porcine embryos.
AB  - Inefficient cloning by somatic cell nuclear transfer (SCNT) is largely attributed
      to defects in epigenetic reprogramming. Reprogramming factors (RFs) (Oct4, Sox2,
      Klf4, c-Myc, Lin28 and Nanog; OSKMLN) can achieve epigenetic reprogramming,
      suggesting that these might facilitate reprogramming of oocytes. Here, porcine
      mesenchymal stem cells (pMSCs) treated with exogenous OSKMLN or OSKM were
      selected as nuclei donors for SCNT. The resulting embryos displayed significantly
      better development than controls in terms of cleavage rates and blastomere
      numbers. OSKM treatment improved pluripotency status and regulation of epigenetic
      factors in modified pMSCs. These changed gene patterns promoted H3K9Ac both in
      modified pMSCs and their SCNT-derived embryos. Thus, higher histone acetylation
      levels in donor cells might favor subsequent clone development. Application of
      exogenous RFs in SCNT offers a novel way for improving cloning efficiency. 

PMID- 24930114
TI  - Characterization of putative glycosylphosphatidylinositol-anchoring motifs for
      surface display in the methylotrophic yeast Hansenula polymorpha.
AB  - Bioinformatic analysis of the genome of the methylotrophic yeast Hansenula
      polymorpha revealed 39 putative glycosylphosphatidylinositol-anchored proteins
      (GPI-proteins). Notably, dibasic motifs in the proximal omega-site, that has been
      reported as a plasma membrane retention signal in Saccharomyces cerevisiae GPI
      proteins, were not found in any of the predicted GPI-proteins of H. polymorpha.
      To evaluate the in silico prediction, C-terminal peptides of 40 amino acids
      derived from ten H. polymorpha GPI-proteins were fused to the Aspergillus saitoi
      alpha-1,2-mannosidase (msdS). Cell wall fraction analysis showed that nine of the
      ten msdS-GPI fusion proteins were mostly localized at the cell wall. Surface
      expression of functional msdS was further confirmed by in vitro enzyme activity
      assay and by glycan structure analysis of cell wall mannoproteins. The
      recombinant H. polymorpha strains expressing surface-displayed msdS have the
      potential as useful hosts to produce glycoproteins with decreased mannosylation. 

PMID- 24930115
TI  - Primary umbilical endometriosis: a case report and review of literature.

PMID- 24930116
TI  - Association of polymorphisms in the 5' untranslated region of RAD51 gene with
      risk of endometrial cancer in the Polish population.
AB  - PURPOSE: Many of the studies have analyzed cell repair capabilities, following
      cancer development. The cellular reaction to DNA damaging agents can modulate the
      susceptibility to various tumors. This reaction is mainly determined by DNA
      repair efficacy which, in turn, may be influenced by the variability of DNA
      repair genes, expressed by their polymorphisms. METHODS: This report describes
      studies of the distribution of genotypes and the frequency of alleles of the
      G135C (rs1801320) and G172T (rs1801321) RAD51 polymorphism in 630 paraffin
      embedded samples of tumor tissue from patients with endometrial cancer. DNA from
      630 normal endometrial tissues served as control. RAD51 polymorphisms were
      determined by PCR-RFLP. RESULTS: In the present work, a relationship was
      identified between RAD51 G135C polymorphism and the incidence of endometrial
      cancer. Endometrial cancer patients had an overrepresentation of 135C allele. The
      135C/C homozygous variant increased cancer risk. A tendency towards a decreased
      risk of endometrial cancer was observed with the occurrence of combined G135C
      G172G genotype of RAD51 polymorphism. An association was confirmed between RAD51
      G135C and G172T polymorphisms and endometrial cancer progression, assessed by the
      histological grades. CONCLUSIONS: The results support the hypothesis that RAD51
      G135C and G172T polymorphisms may be associated with endometrial cancer
      occurrence and/or progression.

PMID- 24930117
TI  - Incidence of emergency peripartum hysterectomy in Ain-shams University Maternity
      Hospital, Egypt: a retrospective study.
AB  - PURPOSE: To estimate the incidence of emergency peripartum hysterectomy over 6
      years in Ain-shams University Maternity Hospital. METHODS: Detailed chart review
      of all cases of emergency peripartum hysterectomy, 2003-2008, including previous
      obstetric history, details of the index pregnancy, indications for emergency
      peripartum hysterectomy, outcome of the hysterectomy and infant morbidity.
      RESULTS: The overall rate of emergency peripartum hysterectomy was 149 of 66,306
      or 2.24 per 1,000 deliveries. The primary indications for hysterectomies were
      placenta accreta/increta 59 (39.6 %), uterine atony 37 (24.8 %), uterine rupture
      35 (23.5 %) and placenta previa without accreta 18 (12.1 %). After hysterectomy,
      115 (77 %) women were admitted to the intensive care unit. Women were discharged
      home after a mean 11.2 day length of stay. Using multifactorial logistic
      regression analysis, we found that woman's age, atonic uterus, placenta
      accreta/increta, previous cesarian section and ruptured uterus were independent
      predictors for peripartum hysterectomy CONCLUSION: Abnormal placentation was the
      main indication for peripartum hysterectomy. The risk factors for peripartum
      hysterectomy were morbid adherence of placentae in scared uteri, uterine atony
      and uterine rupture. The most important step in prevention of major postpartum
      hemorrhage is recognizing and assessing women's risk. The risk of peripartum
      hysterectomy seems to be significantly decreased by limiting the number of
      cesarean section deliveries, thus reducing the occurrence of abnormal
      placentation in the form of placenta accreta, increta or percreta.

PMID- 24930118
TI  - Diffuse uterine leiomyomatosis in patient with successful pregnancy following new
      surgical management.
AB  - Diffuse uterine leiomyomatosis is associated with significant infertility and
      miscarriage complications. Appropriate diagnosis and therapy is essential. A 33
      year-old woman was referred to our hospital because of GnRH analogue treatment
      resistant multiple myomas and infertility. Following new technical myomectomy,
      she conceived spontaneously and delivered a 2,470 g healthy baby by cesarean
      section. New technical myomectomy may become an important conservative treatment
      option for patients with diffuse uterine leiomyomatosis. 

PMID- 24930119
TI  - Enabling membrane protein structure and dynamics with X-ray free electron lasers.
AB  - Determining the three-dimensional structures and dynamics of membrane proteins
      remains one of the great challenges of modern biology. The recent availability of
      X-ray free electron laser (XFEL) light sources has opened the door to a new and
      revolutionary approach to performing X-ray analysis of these important
      biomolecules. Recent advances in sample delivery, data reduction, and phasing
      have enabled the high-resolution structural probing of membrane proteins at room
      temperature. While considerable challenges remain, the recent developments
      described in this review may ultimately provide structural biologists with
      powerful tools for obtaining unprecedented atomic-scale and dynamic visualization
      of membrane proteins at near-physiological conditions.

PMID- 24930120
TI  - Electrical stimulation of lumbar spinal nerve roots in dogs.
AB  - The aim of this study was to test the applicability of electrical stimulation of
      lumbar spinal nerve roots and obtain normative electrical root stimulation (ERS)
      data for L7 nerve root and sciatic nerve in dogs. For that purpose ERS and
      sciatic nerve stimulations were performed consecutively, in totally 40 healthy
      dogs. ERS was applied in the L7/S1 intervertebral space via monopolar needle
      electrodes. Muscle responses were recorded from the gastrocnemius muscles on the
      left and right hind limbs. Sciatic nerve stimulation was performed at the greater
      trochanter level on the left hind limb, with records obtained from the left
      gastrocnemius muscle. Mean root latencies of the left and right side were 5.22 +/
      0.49 ms and 5.29 +/- 0.53 ms, respectively. There was no significant difference
      in root latency between the right and left sides. The mean terminal latency was
      3.82 +/- 0.46 ms. The proximal motor nerve conduction velocity of the sciatic
      nerve was 63.15 +/- 3.43 m/s. The results of this study show that ERS provides
      objective data about the integrity of lumbar spinal nerve roots by evaluating the
      entire population of motor fibres and total length of the motor axon in dogs. ERS
      can be considered a useful diagnostic method for confirmation of diagnoses of
      lumbosacral diseases.

PMID- 24930121
TI  - An observational study of the occurrence of serious adverse reactions among
      patients who receive optison in routine medical practice.
AB  - BACKGROUND: Reports of ultrasound contrast agent safety have been derived mainly
      from retrospective databases rather than from studies specifically designed to
      assess safety. The purpose of this study was to prospectively determine the
      safety of Optison (GE Healthcare, Princeton, NJ) in routine medical practice.
      METHODS: Patients referred for routine rest or stress two-dimensional
      echocardiography who had indications for contrast were enrolled. Vital signs were
      obtained at baseline and at intervals up to 1 hour after dosing of Optison.
      Patients were followed for the development of any serious adverse event (SAE),
      defined as an event that causes death, is life threatening, requires or prolongs
      hospitalization, or causes another important event, for 24 hours after Optison
      administration. RESULTS: A total of 1,039 patients were enrolled, and 76% had 24
      hour follow-up. The median age was 60 years (range, 20-97 years), and 62% were
      men. The mean body mass index was 33 +/- 9 kg/m(2). Patient comorbidities
      included hypertension (73%), hyperlipidemia (64%), smoking (52%), and diabetes
      (37%). There were significant increases in systolic blood pressure, heart rate,
      and respiratory rate between the baseline, 5- to 15-min, 30-min, and 60-min time
      points after the administration of Optison in patients undergoing stress studies
      but none in those undergoing rest studies. There was a total of six SAEs during
      the study, which were felt to be related not to Optison but rather to the stress
      test itself or to the patient's underlying pathology. Although two events were
      classified as SAEs because of hospitalization, the hospitalizations were
      appropriate for pathology that would have been missed without Optison use.
      CONCLUSIONS: In this large, prospective safety study of Optison during routine
      resting and stress echocardiography, no SAEs related to Optison developed.
      Optison helped define abnormalities that required appropriate hospitalization for
      further management.

PMID- 24930122
TI  - The impact of procedural sedation on diagnostic errors in pediatric
      echocardiography.
AB  - BACKGROUND: Infants and young children frequently have difficulty remaining still
      for an echocardiographic examination, potentially leading to poor study quality,
      increasing the likelihood of diagnostic errors. Sedation is believed to improve
      echocardiographic quality, but its effectiveness has not been demonstrated. The
      aim of this study was to test the hypothesis that sedation would improve study
      quality and reduce diagnostic errors. METHODS: Outpatient echocardiograms from
      children aged <=36 months obtained from January 2008 to June 2009 were examined.
      Variables related to image quality, report completeness, and sedation use were
      collected. Diagnostic errors were identified and categorized. Multivariate
      analysis identified the odds ratios (OR) and 95% confidence intervals (CI) for
      risk factors for potentially preventable diagnostic errors and the impact of
      sedation on these errors. RESULTS: Among 2,003 echocardiographic examinations,
      sedation was used in 498 (25%). The overall diagnostic error rate was 6.5%. Most
      errors (66%) were potentially preventable. Multivariate analysis identified the
      following risk factors for potentially preventable errors: precardiac procedure
      (OR, 2.19; 95% CI, 1.05-4.59; P = .04), moderate anatomic complexity (OR, 3.91;
      95% CI, 2.25-6.81; P < .001), and high anatomic complexity (OR, 8.36; 95% CI,
      3.57-19.6; P < .001). Sedation was independently associated with lower odds of
      potentially preventable diagnostic errors (OR, 0.47; 95% CI, 0.27-0.80; P =
      .006). Echocardiographic examinations with sedation had fewer image quality
      concerns (22% vs 60%) and fewer incomplete reports (3% vs 20%) (P < .001).
      CONCLUSIONS: Most echocardiographic diagnostic errors among infants and young
      children are potentially preventable. Sedation is associated with a lower
      likelihood of these diagnostic errors, fewer imaging quality concerns, and fewer
      incomplete reports.

PMID- 24930123
TI  - Initial experience with a novel real-time three-dimensional intracardiac
      ultrasound system to guide percutaneous cardiac structural interventions: a phase
      1 feasibility study of volume intracardiac echocardiography in the assessment of
      patients with structural heart disease undergoing percutaneous transcatheter
      therapy.
AB  - BACKGROUND: Intracardiac echocardiographic (ICE) imaging is a modality
      increasingly used to guide percutaneous cardiac structural interventions. Until
      recently, ICE imaging has been limited by the presence of only two-dimensional
      imaging planes and requires considerable catheter manipulation to visualize
      certain targets. The aim of this study was to assess the feasibility of a new
      three-dimensional (3D) volumetric ICE system to provide imaging guidance in 15
      patients undergoing percutaneous cardiac structural interventions. METHODS: The
      Siemens AcuNav 3D volumetric ICE catheter was used to guide interventions in 15
      patients. Imaging was performed at 6 and 8 MHz without color Doppler flow mapping
      and at 4 and 6 MHz with color Doppler flow mapping. The images were independently
      reviewed, and the ability to visualize specific structures was assessed by two
      independent and expert ICE imagers. RESULTS: The majority of patients (n = 11
      [73%]) were undergoing percutaneous transcatheter closure of patent foramen
      ovales (n = 3 [20%]) or atrial septal defects (n = 8 [53%]). Three patients (20%)
      underwent balloon valvuloplasty for mitral stenosis. One patient (7%) underwent a
      diagnostic study for congenital heart disease. There were no significant
      differences in image scores between 3D and two-dimensional imaging without color
      Doppler in clinically important targets. With color Doppler, there were decreased
      image scores in the 3D images. Three-dimensional images provided improved imaging
      of devices and catheters and of the relationship between atrial septal defect
      devices and the aorta. CONCLUSION: Three-dimensional volumetric ICE imaging can
      be successfully used to guide structural heart disease procedures. It has the
      potential to provide greater anatomic information during interventions. Further
      improvement in its imaging capabilities is required to improve color Doppler
      mapping and volume size capabilities.

PMID- 24930124
TI  - Activation of neuronal nitric oxide synthase (nNOS) signaling pathway in 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced neurotoxicity.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been reported to cause alterations
      in cognitive and motor behavior during both development and adulthood. In this
      study, the neuronal nitric oxide synthase (nNOS) signaling pathway was
      investigated in differentiated pheochromocytoma (PC12) cells to better understand
      the mechanisms of TCDD-induced neurotoxicity. TCDD exposure induced a time- and
      dose-dependent increase in nNOS expression. High levels of nitric oxide (NO)
      production by nNOS activation induced mitochondrial cytochrome c (Cyt-c) release
      and down-regulation of Bcl-2. Additionally, TCDD increased the expression of
      active caspase-3 and significantly led to apoptosis in PC12 cells. However, these
      effects above could be effectively inhibited by the addition of 7-nitroindazole
      (7-NI), a highly selective nNOS inhibitor. Moreover, in the brain cortex of
      Sprague-Dawley (SD) rats, nNOS was also found to have certain relationship with
      TCDD-induced neuronal apoptosis. Together, our findings establish a role for nNOS
      as an enhancer of TCDD-induced apoptosis in PC12 cells. 

PMID- 24930125
TI  - An acute exposure to glyphosate-based herbicide alters aromatase levels in testis
      and sperm nuclear quality.
AB  - Roundup is the major pesticide used in agriculture worldwide; it is a glyphosate
      based herbicide. Its molecular effects are studied following an acute exposure
      (0.5%) of fifteen 60-day-old male rats during an 8-day period. Endocrine
      (aromatase, estrogen and androgen receptors, Gper1 in testicular and sperm mRNAs)
      and testicular functions (organ weights, sperm parameters and expression of the
      blood-testis barrier markers) were monitored at days 68, 87, and 122 after
      treatment, spermiogenesis and spermatogenesis. The major disruption is an
      increase of aromatase mRNA levels at least by 50% in treated rats at all times,
      as well as the aromatase protein. We have also shown a similar increase of Gper1
      expression at day 122 and a light modification of BTB markers. A rise of abnormal
      sperm morphology and a decrease of the expression of protamine 1 and histone 1
      testicular in epididymal sperm are observed despite a normal sperm concentration
      and motility. 

PMID- 24930126
TI  - "Reference values" of trace elements in the hair of a sample group of Spanish
      children (aged 6-9 years) - are urban topsoils a source of contamination?
AB  - Human hair is used as a biomonitor to evaluate the environmental exposure to
      contaminants in the individual. However, the use of human hair is controversial,
      mainly because reference levels for pollutants in hair have not yet been set. In
      the case of Spain, few biomonitoring studies have involved infants and children.
      A biomonitoring study was conducted to investigate the possible normal values of
      trace elements of toxicological concern in children aged 6-9 years from the city
      of Alcala de Henares, Community of Madrid (Spain), following the methodology and
      strict inclusion criteria previously developed by our group. Levels of Al, As,
      Be, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sn, Ti, Tl, V and Zn were monitored in scalp-hair
      from 117 healthy children (47 boys and 70 girls) between April and May of 2001.
      The levels of trace elements here described could be considered as possible
      "reference values" for children aged 6-9 years resident in the Community of
      Madrid. These values might also be selected as a preliminary screening tool to
      evaluate if a Spanish child has been exposed to any of the contaminants studied
      here. This study also investigated whether local urban topsoils were a source of
      metals for this population. 

PMID- 24930127
TI  - Woven Endobridge (WEB) Device for endovascular treatment of ruptured intracranial
      wide-neck aneurysms: a single-center experience.
AB  - INTRODUCTION: Endovascular treatment of ruptured wide-neck bifurcation aneurysms
      presents a challenge. While still under evaluation, the Woven Endobridge (WEB)
      aneurysm embolization system has so far shown promising results in the treatment
      of complex bifurcation aneurysms. We aimed to evaluate the feasibility and short
      term follow-up of endovascular treatment of ruptured wide-neck aneurysm with the
      WEB device. METHODS: Six patients referred to our institution for acute
      symptomatic subarachnoid hemorrhage (SAH) and treated with the WEB device were
      enrolled in this study. Clinical presentations, technical details, intraoperative
      and postoperative complications, and outcomes were recorded. Immediate and 3
      month angiographic results were also evaluated. RESULTS: Three middle cerebral
      artery (MCA) and three anterior communicating artery aneurysms were treated
      between 1 and 14 days after rupturing. Average dome width was 5.8 mm (range 5-7),
      average neck size was 4.5 mm (range 4-5), and average dome-to-neck ratio was 1.3
      (range 1-1.7). The WEB system was the exclusive treatment and was successfully
      deployed in all cases. Per procedural thromboembolic events occurred in two cases
      and were treated with intra-arterial administration of antiplatelet agents
      without any clinical consequences. The modified Rankin Scale (mRS) score at
      discharge was 0 for all patients. The 3-month angiographic follow-up showed
      adequate occlusion in four of our six patients (67 %). CONCLUSION: From this
      preliminary study, the high feasibility rate and lack of need for systematic
      antiplatelet agents favor the WEB device providing a solution for endovascular
      treatment of ruptured wide-neck bifurcation aneurysms during the acute phase.
      However, further studies are needed to evaluate the complication rate and long
      term efficiency.

PMID- 24930128
TI  - Hemorrhage rates and risk factors in the natural history course of brain
      arteriovenous malformations.
AB  - Brain arteriovenous malformations (AVMs) are abnormal connections of arteries and
      veins, resulting in arteriovenous shunting of blood. Primary medical therapy is
      lacking; treatment options include surgery, radiosurgery, and embolization, often
      in combination. Judicious selection of AVM patients for treatment requires
      balancing risk of treatment complications against the risk of hemorrhage in the
      natural history course. This review focuses on the epidemiology, hemorrhage risk,
      and factors influencing risk of hemorrhage in the untreated natural course
      associated with sporadic brain AVM. 

PMID- 24930129
TI  - Protein delivery into live cells by incubation with an endosomolytic agent.
AB  - We report that a tetramethylrhodamine-labeled dimer of the cell-penetrating
      peptide TAT, dfTAT, penetrates live cells by escaping from endosomes with high
      efficiency. By mediating endosomal leakage, dfTAT also delivers proteins into
      cultured cells after a simple co-incubation procedure. We achieved cytosolic
      delivery in several cell lines and primary cells and observed that only a
      relatively small amount of material remained trapped inside endosomes. Delivery
      did not require a binding interaction between dfTAT and a protein, multiple
      molecules could be delivered simultaneously, and delivery could be repeated.
      dfTAT-mediated delivery did not noticeably affect cell viability, cell
      proliferation or gene expression. dfTAT-based intracellular delivery should be
      useful for cell-based assays, cellular imaging applications and the ex vivo
      manipulation of cells. 

PMID- 24930130
TI  - Chemically defined generation of human cardiomyocytes.
AB  - Existing methods for human induced pluripotent stem cell (hiPSC) cardiac
      differentiation are efficient but require complex, undefined medium constituents
      that hinder further elucidation of the molecular mechanisms of cardiomyogenesis.
      Using hiPSCs derived under chemically defined conditions on synthetic matrices,
      we systematically developed an optimized cardiac differentiation strategy, using
      a chemically defined medium consisting of just three components: the basal medium
      RPMI 1640, L-ascorbic acid 2-phosphate and rice-derived recombinant human
      albumin. Along with small molecule-based induction of differentiation, this
      protocol produced contractile sheets of up to 95% TNNT2(+) cardiomyocytes at a
      yield of up to 100 cardiomyocytes for every input pluripotent cell and was
      effective in 11 hiPSC lines tested. This chemically defined platform for cardiac
      specification of hiPSCs will allow the elucidation of cardiomyocyte
      macromolecular and metabolic requirements and will provide a minimal system for
      the study of maturation and subtype specification. 

PMID- 24930131
TI  - Neck strength: a protective factor reducing risk for concussion in high school
      sports.
AB  - As the number of high school students participating in athletics continues to
      increase, so will the number of sports-related concussions unless effective
      concussion prevention programs are developed. We sought to develop and validate a
      cost-effective tool to measure neck strength in a high school setting, conduct a
      feasibility study to determine if the developed tool could be reliably applied by
      certified athletic trainers (ATs) in a high school setting, and conduct a pilot
      study to determine if anthropometric measurements captured by ATs can predict
      concussion risk. In the study's first phase, 16 adult subjects underwent repeated
      neck strength testing by a group of five ATs to validate the developed hand-held
      tension scale, a cost effective alternative to a hand-held dynamometer. In the
      second phase, during the 2010 and 2011 academic years, ATs from 51 high schools
      in 25 states captured pre-season anthropometric measurements for 6,704 high
      school athletes in boys' and girls' soccer, basketball, and lacrosse, as well as
      reported concussion incidence and athletic exposure data. We found high
      correlations between neck strength measurements taken with the developed tool and
      a hand-held dynamometer and the measurements taken by five ATs. Smaller mean neck
      circumference, smaller mean neck to head circumference ratio, and weaker mean
      overall neck strength were significantly associated with concussion. Overall neck
      strength (p < 0.001), gender (p < 0.001), and sport (p = 0.007) were significant
      predictors of concussions in unadjusted models. After adjusting for gender and
      sport, overall neck strength remained a significant predictor of concussion (p =
      0.004). For every one pound increase in neck strength, odds of concussion
      decreased by 5 % (OR = 0.95, 95 % CI 0.92-0.98). We conclude that identifying
      differences in overall neck strength may be useful in developing a screening tool
      to determine which high school athletes are at higher risk of concussion. Once
      identified, these athletes could be targeted for concussion prevention programs.

PMID- 24930132
TI  - Propensity scores-potential outcomes framework to incorporate severity
      probabilities in the highway safety manual crash prediction algorithm.
AB  - Accurate estimation of the expected number of crashes at different severity
      levels for entities with and without countermeasures plays a vital role in
      selecting countermeasures in the framework of the safety management process. The
      current practice is to use the American Association of State Highway and
      Transportation Officials' Highway Safety Manual crash prediction algorithms,
      which combine safety performance functions and crash modification factors, to
      estimate the effects of safety countermeasures on different highway and street
      facility types. Many of these crash prediction algorithms are based solely on
      crash frequency, or assume that severity outcomes are unchanged when planning
      for, or implementing, safety countermeasures. Failing to account for the
      uncertainty associated with crash severity outcomes, and assuming crash severity
      distributions remain unchanged in safety performance evaluations, limits the
      utility of the Highway Safety Manual crash prediction algorithms in assessing the
      effect of safety countermeasures on crash severity. This study demonstrates the
      application of a propensity scores-potential outcomes framework to estimate the
      probability distribution for the occurrence of different crash severity levels by
      accounting for the uncertainties associated with them. The probability of fatal
      and severe injury crash occurrence at lighted and unlighted intersections is
      estimated in this paper using data from Minnesota. The results show that the
      expected probability of occurrence of fatal and severe injury crashes at a
      lighted intersection was 1 in 35 crashes and the estimated risk ratio indicates
      that the respective probabilities at an unlighted intersection was 1.14 times
      higher compared to lighted intersections. The results from the potential outcomes
      propensity scores framework are compared to results obtained from traditional
      binary logit models, without application of propensity scores matching.
      Traditional binary logit analysis suggests that the probability of occurrence of
      severe injury crashes is higher at lighted intersections compared to unlighted
      intersections, which contradicts the findings obtained from the propensity scores
      potential outcomes framework. This finding underscores the importance of having
      comparable treated and untreated entities in traffic safety countermeasure
      evaluations. 

PMID- 24930133
TI  - Tensile bond strength of resin composite repair in vitro using different surface
      preparation conditionings to an aged CAD/CAM resin nanoceramic.
AB  - OBJECTIVES: This study was conducted in order to assess the pretreatment method
      (air abrasion, both wet and dry, and Al2O3 grinder), the conditioning method
      (comprised of different adhesive systems), the repair resin composite (low and
      high modulus of elasticity), the contamination of CoJet air-abraded surfaces with
      water, and the effect phosphoric acid on the macrotensile bond strength (TBS) to
      aged CAD/CAM resin nanoceramic (RNC). MATERIALS AND METHODS: Aged RNC substrates
      (LAVA Ultimate, 3M ESPE; N = 900; 10,000 cycles, 5  degrees C/55  degrees C) were
      air-abraded (CoJet 3M ESPE) with and without water contamination or treated with
      an Al2O3 grinder (Cimara, Voco). Immediately after pretreatment, half of the
      specimens were additionally cleaned with phosphoric acid, while the rest were
      only rinsed with water. Four intermediate agents (Futurabond U/VOCO, Scotchbond
      Universal/3M ESPE, One Coat Bond/Coltene Whaledent, visio.link/bredent) were
      selected for conditioning the surface, while no conditioned specimens acted as
      control groups. Specimens were thereafter repaired using two direct resin
      composites (Arabesk Top and GrandioSo, VOCO), stored for 24 h at 37  degrees C in
      H2O, and thermally aged for 10,000 cycles (5  degrees C/55  degrees C; n =
      15/subgroup). TBS and failure types were determined and evaluated with four- and
      one-way ANOVA and chi (2) test (p < 0.05). RESULTS: The highest influence on TBS
      was exerted by the conditioning method (partial eta-squared (eta P (2)) = 0.273,
      p < 0.05), followed by the resin composite repair (eta P (2) = 0.07, p < 0.05)
      and the surface pretreatment method (eta P (2) = 0.032, p < 0.05), while an acid
      contamination after surface pretreatment was insignificant (p = 0.154).
      CONCLUSIONS: Air abrasion produced superior TBS compared to grinding of the
      surface with Al2O3 prior to repair. The tested universal adhesives proved to be
      effective intermediate agents for repairing aged CAD/CAM RNC, while visio.link
      and Scotchbond Universal performed slightly better than Futurabond U. CLINICAL
      RELEVANCE: Phosphoric acid or water contamination of the air-abraded surface does
      not affect the repair bond strength.

PMID- 24930135
TI  - Extended use of the GuideLiner in complex coronary interventions.
AB  - AIMS: Challenging coronary anatomies including chronic total occlusions (CTO),
      extreme vessel tortuosity, diseased bypass grafts, and anomalous coronary
      arteries pose difficulties in coronary interventions. The GuideLiner is a
      monorail catheter originally developed to facilitate delivery of stents to target
      lesions in tortuous vessels. We conducted a study on the feasibility and safety
      of utilising this catheter in a wider array of complex coronary interventions.
      METHODS AND RESULTS: Consecutive patients undergoing coronary or peripheral
      interventions where a GuideLiner was used were recruited into this study. Patient
      demographics, lesion and vessel characteristics, procedural details and outcomes
      were prospectively entered into our database and analysed. From September 2009 to
      October 2011, 54 consecutive patients underwent coronary intervention in our
      institution using a GuideLiner; 21 out of 54 coronary applications were motivated
      by the need to increase support to cross CTOs, predominantly of the RCA.
      Anomalous or angulated take-off of the treatment vessels (31%), previously
      deployed proximal stents (15%), heavy proximal calcification (9%) and tortuosity
      (7%) accounted for the remaining reasons. One patient had successful renal
      denervation with the aid of a GuideLiner catheter. Procedural success was 98% in
      our series with no device-related periprocedural complications such as ostial
      dissection or myocardial necrosis. CONCLUSIONS: The use of a GuideLiner
      facilitates the approach to complex coronary interventions including chronic
      total occlusion and saphenous vein graft intervention by providing greater back
      up support and easier engagement of coronary ostia.

PMID- 24930134
TI  - Expression of DNA repair genes in burned skin exposed to low-level red laser.
AB  - Although red laser lights lie in the region of non-ionizing radiations in the
      electromagnetic spectrum, there are doubts whether absorption of these radiations
      causes lesions in the DNA molecule. Our aim was to investigate the expression of
      the genes involved with base excision and nucleotide excision repair pathways in
      skin tissue submitted to burn injury and exposed to low-level red laser. Wistar
      rats were divided as follows: control group-rats burned and not irradiated, laser
      group-rats burned and irradiated 1 day after injury for five consecutive days,
      and later laser group-rats injured and treated 4 days after injury for five
      consecutive days. Irradiation was performed according to a clinical protocol (20
      J/cm(2), 100 mW, continuous wave emission mode). The animals were sacrificed on
      day 10, and scarred tissue samples were withdrawn for total RNA extraction,
      complementary DNA (cDNA) synthesis, and evaluation of gene expression by
      quantitative polymerase chain reaction. Low-level red laser exposure (1) reduces
      the expression of APE1 messenger (mRNA), (2) increases the expression of OGG1
      mRNA, (3) reduces the expression of XPC mRNA, and (4) increases the expression of
      XPA mRNA both in laser and later laser groups. Red laser exposure at therapeutic
      fluences alters the expression of genes related to base excision and nucleotide
      excision pathways of DNA repair during wound healing of burned skin.

PMID- 24930136
TI  - The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced
      skin toxicity.
AB  - This open-labeled phase II, efficacy-finding study evaluated the efficiency and
      safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who
      developed cetuximab induced skin toxicity. Patients who received cetuximab plus
      chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily
      with a soap made of oil extracted from Pistacia terebinthus. During treatment, no
      topical or oral antibiotics, corticosteroids or other moisturizers were used.
      Patients were examined 1 week later and their photographs were taken. Fifteen
      mCRC patients who developed skin toxicity while receiving first-line CTX in
      combination with chemotherapy were included into the study. Eight patients were
      male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had
      Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade
      3 skin toxicities were 100 and 33%, respectively. In the remaining patients with
      Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response
      rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment
      due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when
      patients stopped administering the soap and therefore they used it throughout the
      cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and
      effectively in the treatment of skin toxicity induced by Cetuximab.

PMID- 24930137
TI  - Evolutionary analysis identifies an MX2 haplotype associated with natural
      resistance to HIV-1 infection.
AB  - The protein product of the myxovirus resistance 2 (MX2) gene restricts HIV-1 and
      simian retroviruses. We demonstrate that MX2 evolved adaptively in mammals with
      distinct sites representing selection targets in distinct branches; selection
      mainly involved residues in loop 4, previously shown to carry antiviral
      determinants. Modeling data indicated that positively selected sites form a
      continuous surface on loop 4, which folds into two antiparallel alpha-helices
      protruding from the stalk domain. A population genetics-phylogenetics approach
      indicated that the coding region of MX2 mainly evolved under negative selection
      in the human lineage. Nonetheless, population genetic analyses demonstrated that
      natural selection operated on MX2 during the recent history of human populations:
      distinct selective events drove the frequency increase of two haplotypes in the
      populations of Asian and European ancestry. The Asian haplotype carries a
      susceptibility allele for melanoma; the European haplotype is tagged by
      rs2074560, an intronic variant. Analyses performed on three independent European
      cohorts of HIV-1-exposed seronegative individuals with different geographic
      origin and distinct exposure route showed that the ancestral (G) allele of
      rs2074560 protects from HIV-1 infection with a recessive effect (combined P =
      1.55 * 10(-4)). The same allele is associated with lower in vitro HIV-1
      replication and increases MX2 expression levels in response to IFN-alpha. Data
      herein exploit evolutionary information to identify a novel host determinant of
      HIV-1 infection susceptibility. 

PMID- 24930138
TI  - The Scramble conversion tool.
AB  - MOTIVATION: The reference CRAM file format implementation is in Java. We present
      'Scramble': a new C implementation of SAM, BAM and CRAM file I/O. RESULTS: The C
      implementation of for CRAM is 1.5-1.7* slower than BAM at decoding but 1.8-2.6*
      faster at encoding. We see file size savings of 34-55%. AVAILABILITY AND
      IMPLEMENTATION: Source code is available at
      http://sourceforge.net/projects/staden/files/io_lib/ under the BSD software
      licence.

PMID- 24930139
TI  - circlize Implements and enhances circular visualization in R.
AB  - SUMMARY: Circular layout is an efficient way for the visualization of huge
      amounts of genomic information. Here we present the circlize package, which
      provides an implementation of circular layout generation in R as well as an
      enhancement of available software. The flexibility of this package is based on
      the usage of low-level graphics functions such that self-defined high-level
      graphics can be easily implemented by users for specific purposes. Together with
      the seamless connection between the powerful computational and visual environment
      in R, circlize gives users more convenience and freedom to design figures for
      better understanding genomic patterns behind multi-dimensional data. AVAILABILITY
      AND IMPLEMENTATION: circlize is available at the Comprehensive R Archive Network
      (CRAN): http://cran.r-project.org/web/packages/circlize/

PMID- 24930140
TI  - miR-PREFeR: an accurate, fast and easy-to-use plant miRNA prediction tool using
      small RNA-Seq data.
AB  - SUMMARY: Plant microRNA prediction tools that use small RNA-sequencing data are
      emerging quickly. These existing tools have at least one of the following
      problems: (i) high false-positive rate; (ii) long running time; (iii) work only
      for genomes in their databases; (iv) hard to install or use. We developed miR
      PREFeR (miRNA PREdiction From small RNA-Seq data), which uses expression patterns
      of miRNA and follows the criteria for plant microRNA annotation to accurately
      predict plant miRNAs from one or more small RNA-Seq data samples of the same
      species. We tested miR-PREFeR on several plant species. The results show that miR
      PREFeR is sensitive, accurate, fast and has low-memory footprint. AVAILABILITY
      AND IMPLEMENTATION: https://github.com/hangelwen/miR-PREFeR

PMID- 24930141
TI  - Cloud4Psi: cloud computing for 3D protein structure similarity searching.
AB  - SUMMARY: Popular methods for 3D protein structure similarity searching,
      especially those that generate high-quality alignments such as Combinatorial
      Extension (CE) and Flexible structure Alignment by Chaining Aligned fragment
      pairs allowing Twists (FATCAT) are still time consuming. As a consequence,
      performing similarity searching against large repositories of structural data
      requires increased computational resources that are not always available. Cloud
      computing provides huge amounts of computational power that can be provisioned on
      a pay-as-you-go basis. We have developed the cloud-based system that allows
      scaling of the similarity searching process vertically and horizontally.
      Cloud4Psi (Cloud for Protein Similarity) was tested in the Microsoft Azure cloud
      environment and provided good, almost linearly proportional acceleration when
      scaled out onto many computational units. AVAILABILITY AND IMPLEMENTATION:
      Cloud4Psi is available as Software as a Service for testing purposes at:
      http://cloud4psi.cloudapp.net/. For source code and software availability, please
      visit the Cloud4Psi project home page at
      http://zti.polsl.pl/dmrozek/science/cloud4psi.htm.

PMID- 24930142
TI  - Evaluation and validation of de novo and hybrid assembly techniques to derive
      high-quality genome sequences.
AB  - MOTIVATION: To assess the potential of different types of sequence data combined
      with de novo and hybrid assembly approaches to improve existing draft genome
      sequences. RESULTS: Illumina, 454 and PacBio sequencing technologies were used to
      generate de novo and hybrid genome assemblies for four different bacteria, which
      were assessed for quality using summary statistics (e.g. number of contigs, N50)
      and in silico evaluation tools. Differences in predictions of multiple copies of
      rDNA operons for each respective bacterium were evaluated by PCR and Sanger
      sequencing, and then the validated results were applied as an additional
      criterion to rank assemblies. In general, assemblies using longer PacBio reads
      were better able to resolve repetitive regions. In this study, the combination of
      Illumina and PacBio sequence data assembled through the ALLPATHS-LG algorithm
      gave the best summary statistics and most accurate rDNA operon number
      predictions. This study will aid others looking to improve existing draft genome
      assemblies. AVAILABILITY AND IMPLEMENTATION: All assembly tools except CLC
      Genomics Workbench are freely available under GNU General Public License.
      CONTACT: brownsd@ornl.gov SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 24930143
TI  - LICRE: unsupervised feature correlation reduction for lipidomics.
AB  - MOTIVATION: Recent advances in high-throughput lipid profiling by liquid
      chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS)
      have made it possible to quantify hundreds of individual molecular lipid species
      (e.g. fatty acyls, glycerolipids, glycerophospholipids, sphingolipids) in a
      single experimental run for hundreds of samples. This enables the lipidome of
      large cohorts of subjects to be profiled to identify lipid biomarkers
      significantly associated with disease risk, progression and treatment response.
      Clinically, these lipid biomarkers can be used to construct classification models
      for the purpose of disease screening or diagnosis. However, the inclusion of a
      large number of highly correlated biomarkers within a model may reduce
      classification performance, unnecessarily inflate associated costs of a diagnosis
      or a screen and reduce the feasibility of clinical translation. An unsupervised
      feature reduction approach can reduce feature redundancy in lipidomic biomarkers
      by limiting the number of highly correlated lipids while retaining informative
      features to achieve good classification performance for various clinical
      outcomes. Good predictive models based on a reduced number of biomarkers are also
      more cost effective and feasible from a clinical translation perspective.
      RESULTS: The application of LICRE to various lipidomic datasets in diabetes and
      cardiovascular disease demonstrated superior discrimination in terms of the area
      under the receiver operator characteristic curve while using fewer lipid markers
      when predicting various clinical outcomes. AVAILABILITY AND IMPLEMENTATION: The
      MATLAB implementation of LICRE is available from
      http://ww2.cs.mu.oz.au/~gwong/LICRE

PMID- 24930144
TI  - Improving the accuracy of the structure prediction of the third hypervariable
      loop of the heavy chains of antibodies.
AB  - MOTIVATION: Antibodies are able to recognize a wide range of antigens through
      their complementary determining regions formed by six hypervariable loops.
      Predicting the 3D structure of these loops is essential for the analysis and
      reengineering of novel antibodies with enhanced affinity and specificity. The
      canonical structure model allows high accuracy prediction for five of the loops.
      The third loop of the heavy chain, H3, is the hardest to predict because of its
      diversity in structure, length and sequence composition. RESULTS: We describe a
      method, based on the Random Forest automatic learning technique, to select
      structural templates for H3 loops among a dataset of candidates. These can be
      used to predict the structure of the loop with a higher accuracy than that
      achieved by any of the presently available methods. The method also has the
      advantage of being extremely fast and returning a reliable estimate of the model
      quality. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at
      http://www.biocomputing.it/H3Loopred/ .

PMID- 24930146
TI  - Retraction.

PMID- 24930147
TI  - Reply: To PMID 24762160.

PMID- 24930145
TI  - TIPdb-3D: the three-dimensional structure database of phytochemicals from Taiwan
      indigenous plants.
AB  - The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for
      biologically active phytochemicals. Based on our TIPdb database curating
      bioactive phytochemicals from Taiwan indigenous plants, this study presents a
      three-dimensional (3D) chemical structure database named TIPdb-3D to support the
      discovery of novel pharmacologically active compounds. The Merck Molecular Force
      Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The
      3D structures could facilitate the analysis of 3D quantitative structure-activity
      relationship, the exploration of chemical space and the identification of
      potential pharmacologically active compounds using protein-ligand docking.
      Database URL: http://cwtung.kmu.edu.tw/tipdb. 

PMID- 24930148
TI  - [...is better than cure].

PMID- 24930149
TI  - [Teaching practice recommendations: prevention and screening].
AB  - The aim of this article is to provide guidance to family doctors on how to tutor
      students about effective screening and primary prevention. Family doctors know
      their patients and adapt national and international guidelines to their specific
      context, risk profile, sex and age as well as to the prevalence of the disorders
      under consideration. Three cases are presented to illustrate guideline use
      according to the level of evidence (for a 19-year-old man, a 60-year-old woman,
      and an 80-year-old man). A particular strength of family medicine is that doctors
      see their patients over the years. Thus they can progressively go through the
      various prevention strategies, screening, counselling and immunisation,
      accompanying their patients with precious advice for their health throughout
      their lifetime.

PMID- 24930150
TI  - [Quaternary prevention: is acting always justified in family medicine?].
AB  - Quaternary prevention aims to protect the patient or population against
      overmedicalisation. Quaternary prevention influences all the activities of family
      medicine by questioning the utility of primary prevention and early diagnosis,
      identifying the risks of creating new pathological entities and practicing a
      maximalist medicine. Family doctors can support quaternary prevention by focusing
      on their patients' priorities and the local resources of an efficient health
      system.

PMID- 24930151
TI  - [Health counseling in primary care doctors' offices: a new wind! The Health
      Coaching Program of the Swiss College of Primary Care Medicine].
AB  - The Health Coaching Program facilitates health behavior counseling in all areas
      of primary medical care: prevention, therapy and rehabilitation, i.e. wherever
      the patient is the decisive agent of change. Health Coaching gives the patient
      the main role. The physician becomes his coach. Health Coaching offers skills
      training and simple algorithms with a colour-coded visual tool to assist patient
      and physician through the 4 steps of developing awareness, building motivation,
      preparing a personal health project and implementing it. Health Coaching was
      tested successfully by 20 family doctors during 12 months: of 1045 patients
      invited 91% enrolled; 37% completed all four steps; one half achieved a positive
      behavior change. Acceptance and feasibility were high in physicians and patients.
      Nationwide dissemination is now in preparation.

PMID- 24930152
TI  - [Prevention of binge drinking in adolescents: do family doctors have a role to
      play?].
AB  - Binge drinking has nearly become the norm for young people and is thus worrying.
      Although alcohol use in males attracts more media attention, females are also
      frequently affected. A variety of preventive measures can be proposed: at the
      individual level by parents, peers and family doctors; at the school and
      community level, particularly to postpone age of first use and first episode of
      drunkenness; at the structural level through a policy restricting access to
      alcohol for young people and increasing its price. Family doctors can play an
      important role in identifying at risk users and individualising preventive
      messages to which these young people are exposed in other contexts.

PMID- 24930153
TI  - [Preventing work-related health problems: the work of the ergonomist].
AB  - Preventing work-related health problems is an important aspect when considering
      clinical symptoms. Analysing a person's professional activity is a complex task.
      The ergonomist intervenes to understand the details of the organisational,
      environmental and cognitive structures that influence health. The case of a pre
      school educator with back pain is presented here as an example of how such a
      situation is studied and concrete solutions instated. Health preservation
      strategies, facilitating factors and barriers were identified, which led to a
      reduction in straining, improved organisation of tasks and achievement of
      educational goals.

PMID- 24930154
TI  - [Management of the esophageal candidiasis by the primary care physician].
AB  - Esophageal candidiasis is one of the most common opportunistic infections in
      patients infected by human immunodeficiency virus (HIV). This pathology is also
      found in patients without overt immunodeficiency. Other risk factors are known to
      be associated with this disease like inhaled or systemic corticosteroid treatment
      or proton-pump inhibitors and H2 receptor antagonists. In the absence of
      identified risk factors, a primary immune deficiency should be sought. Prevention
      of esophageal candidiasis is based primarily on the identification of risk
      factors, and a better control of them. This article presents a review of the
      physiopathology, clinical presentation and management of esophageal candidiasis
      by primary care physicians. We will also discuss ways of preventing esophageal
      candidiasis when necessary.

PMID- 24930155
TI  - [Pseudo-Kaposi revealing an algodystrophy].

PMID- 24930156
TI  - [Medical confidentiality in prison: the third victim?].

PMID- 24930157
TI  - [The truth spoken in what is said, says something different from what you mean].

PMID- 24930158
TI  - [Statins: details].

PMID- 24930159
TI  - [Response].

PMID- 24930160
TI  - [The European Union faces an epidemic of viral diarrhea from American pigs].

PMID- 24930161
TI  - [37 millions of lives almost at hand...].

PMID- 24930162
TI  - [End of life: who really decides on the Old Continent?].

PMID- 24930163
TI  - [Vitamin D and the prevention of falls: called into question?].

PMID- 24930164
TI  - [Fecal microbiota transplantation: details of the first French tests].

PMID- 24930165
TI  - [Declinations of nihilism].

PMID- 24930166
TI  - Thoughts in flight: automation use and pilots' task-related and task-unrelated
      thought.
AB  - OBJECTIVE: The objective was to examine the relationship between cockpit
      automation use and task-related and task-unrelated thought among airline pilots.
      BACKGROUND: Studies find that cockpit automation can sometimes relieve pilots of
      tedious control tasks and afford them more time to think ahead. Paradoxically,
      automation has also been shown to lead to lesser awareness. These results prompt
      the question of what pilots think about while using automation. METHOD: A total
      of 18 airline pilots flew a Boeing 747-400 simulator while we recorded which of
      two levels of automation they used. As they worked, pilots were verbally probed
      about what they were thinking. Pilots were asked to categorize their thoughts as
      pertaining to (a) a specific task at hand, (b) higher-level flight-related
      thoughts (e.g.,planning ahead), or (c) thoughts unrelated to the flight. Pilots'
      performance was also measured. RESULTS: Pilots reported a smaller percentage of
      task-at-hand thoughts (27% vs. 50%) and a greater percentage of higher-level
      flight-related thoughts (56% vs. 29%) when using the higher level of automation.
      However, when all was going according to plan, using either level of automation,
      pilots also reported a higher percentage of task-unrelated thoughts (21%) than
      they did when in the midst of an unsuccessful performance (7%). Task-unrelated
      thoughts peaked at 25% when pilots were not interacting with the automation.
      CONCLUSION: Although cockpit automation may provide pilots with more time to
      think, it may encourage pilots to reinvest only some of this mental free time in
      thinking flight-related thoughts. APPLICATION: This research informs the design
      of human-automation systems that more meaningfully engage the human operator.

PMID- 24930167
TI  - Are gamers better crossers? An examination of action video game experience and
      dual task effects in a simulated street crossing task.
AB  - OBJECTIVE: A high-fidelity street crossing simulator was used to test the
      hypothesis that experienced action video game players are less vulnerable than
      non-gamers to dual task costs in complex tasks. BACKGROUND: Previous research has
      shown that action video game players outperform nonplayers on many single task
      measures of perception and attention. It is unclear, however, whether action
      video game players outperform nonplayers in complex, divided attention tasks.
      METHOD: Experienced action video game players and nongamers completed a street
      crossing task in a high-fidelity simulator. Participants walked on a manual
      treadmill to cross the street. During some crossings, a cognitively demanding
      working memory task was added. RESULTS: Dividing attention resulted in more
      collisions and increased decision making time. Of importance, these dual task
      costs were equivalent for the action video game players and the nongamers.
      CONCLUSION: These results suggest that action video game players are equally
      susceptible to the costs of dividing attention in a complex task. APPLICATION:
      Perceptual and attentional benefits associated with action video game experience
      may not translate to performance benefits in complex, real-world tasks.

PMID- 24930168
TI  - A strategically timed verbal task improves performance and neurophysiological
      alertness during fatiguing drives.
AB  - OBJECTIVE: The objective of this study was to investigate if a verbal task can
      improve alertness and if performance changes are associated with changes in
      alertness as measured by EEG. BACKGROUND: Previous research has shown that a
      secondary task can improve performance on a short, monotonous drive. The current
      work extends this by examining longer, fatiguing drives. The study also uses EEG
      to confirm that improved driving performance is concurrent with improved driver
      alertness. METHOD: A 90-min, monotonous simulator drive was used to place drivers
      in a fatigued state. Four secondary tasks were used: no verbal task, continuous
      verbal task, late verbal task, and a passive radio task. RESULTS: When engaged in
      a secondary verbal task at the end of the drive, drivers showed improved lane
      keeping performance and had improvements in neurophysiological measures of
      alertness. CONCLUSION: A strategically timed concurrent task can improve
      performance even for fatiguing drives. APPLICATION: Secondary-task
      countermeasures may prove useful for enhancing driving performance across a range
      of driving conditions.

PMID- 24930169
TI  - Team performance in networked supervisory control of unmanned air vehicles:
      effects of automation, working memory, and communication content.
AB  - OBJECTIVE: Assess team performance within a net-worked supervisory control
      setting while manipulating automated decision aids and monitoring team
      communication and working memory ability. BACKGROUND: Networked systems such as
      multi-unmanned air vehicle (UAV) supervision have complex properties that make
      prediction of human-system performance difficult. Automated decision aid can
      provide valuable information to operators, individual abilities can limit or
      facilitate team performance, and team communication patterns can alter how
      effectively individuals work together. We hypothesized that reliable automation,
      higher working memory capacity, and increased communication rates of task
      relevant information would offset performance decrements attributed to high task
      load. METHOD: Two-person teams performed a simulated air defense task with two
      levels of task load and three levels of automated aid reliability. Teams
      communicated and received decision aid messages via chat window text messages.
      RESULTS: Task Load x Automation effects were significant across all performance
      measures. Reliable automation limited the decline in team performance with
      increasing task load. Average team spatial working memory was a stronger
      predictor than other measures of team working memory. Frequency of team rapport
      and enemy location communications positively related to team performance, and
      word count was negatively related to team performance. CONCLUSION: Reliable
      decision aiding mitigated team performance decline during increased task load
      during multi-UAV supervisory control. Team spatial working memory, communication
      of spatial information, and team rapport predicted team success. APPLICATION: An
      automated decision aid can improve team performance under high task load.
      Assessment of spatial working memory and the communication of task-relevant
      information can help in operator and team selection in supervisory control
      systems.

PMID- 24930170
TI  - Human performance consequences of stages and levels of automation: an integrated
      meta-analysis.
AB  - OBJECTIVE: We investigated how automation-induced human performance consequences
      depended on the degree of automation (DOA). BACKGROUND: Function allocation
      between human and automation can be represented in terms of the stages and levels
      taxonomy proposed by Parasuraman, Sheridan, and Wickens. Higher DOAs are achieved
      both by later stages and higher levels within stages. METHOD: A meta-analysis
      based on data of 18 experiments examines the mediating effects of DOA on routine
      system performance, performance when the automation fails, workload, and
      situation awareness (SA). The effects of DOA on these measures are summarized by
      level of statistical significance. RESULTS: We found (a) a clear automation
      benefit for routine system performance with increasing DOA, (b) a similar but
      weaker pattern for workload when automation functioned properly, and (c) a
      negative impact of higher DOA on failure system performance and SA. Most
      interesting was the finding that negative consequences of automation seem to be
      most likely when DOA moved across a critical boundary, which was identified
      between automation supporting information analysis and automation supporting
      action selection. CONCLUSION: Results support the proposed cost-benefit trade-off
      with regard to DOA. It seems that routine performance and workload on one hand,
      and the potential loss of SA and manual skills on the other hand, directly trade
      off and that appropriate function allocation can serve only one of the two
      aspects. APPLICATION: Findings contribute to the body of research on adequate
      function allocation by providing an overall picture through quantitatively
      combining data from a variety of studies across varying domains.

PMID- 24930171
TI  - The construct of state-level suspicion: a model and research agenda for automated
      and information technology (IT) contexts.
AB  - OBJECTIVE: The objective was to review and integrate available research about the
      construct of state-level suspicion as it appears in social science literatures
      and apply the resulting findings to information technology (IT) contexts.
      BACKGROUND: Although the human factors literature is replete with articles about
      trust (and distrust) in automation, there is little on the related, but distinct,
      construct of "suspicion" (in either automated or IT contexts). The construct of
      suspicion--its precise definition, theoretical correlates, and role in such
      applications--deserves further study. METHOD: Literatures that consider suspicion
      are reviewed and integrated. Literatures include communication, psychology, human
      factors, management, marketing, information technology, and brain/neurology. We
      first develop a generic model of state-level suspicion. Research propositions are
      then derived within IT contexts. RESULTS: Fundamental components of suspicion
      include (a) uncertainty, (b) increased cognitive processing (e.g., generation of
      alternative explanations for perceived discrepancies), and (c) perceptions of
      (mal)intent. State suspicion is defined as the simultaneous occurrence of these
      three components. Our analysis also suggests that trust inhibits suspicion,
      whereas distrust can be a catalyst of state-level suspicion. Based on a three
      stage model of state-level suspicion, associated research propositions and
      questions are developed. These propositions and questions are intended to help
      guide future work on the measurement of suspicion (self-report and neurological),
      as well as the role of the construct of suspicion in models of decision making
      and detection of deception. CONCLUSION: The study of suspicion, including its
      correlates, antecedents, and consequences, is important. We hope that the social
      sciences will benefit from our integrated definition and model of state
      suspicion. The research propositions regarding suspicion in IT contexts should
      motivate substantial research in human factors and related fields.

PMID- 24930172
TI  - Visualizing uncertainty: the impact on performance.
AB  - OBJECTIVE: This work investigated the impact of uncertainty representation on
      performance in a complex authentic visualization task, submarine localization.
      BACKGROUND: Because passive sonar does not provide unique course, speed, and
      range information on a contact, the submarine operates under significant
      uncertainty. There are many algorithms designed to address this problem, but all
      are subject to uncertainty. The extent of this solution uncertainty can be
      expressed in several ways, including a table of locations (course, speed, range)
      or a graphical area of uncertainty. METHOD: To test the hypothesis that the
      representation of uncertainty that more closely matches the experts' preferred
      representation of the problem would better support performance, even for the
      nonexpert, performance data were collected using displays that were either
      stripped of the spatial or the tabular representation. RESULTS: Performance was
      more accurate when uncertainty was displayed spatially. This effect was only
      significant for the nonexperts for whom the spatial displays supported almost
      expert-like performance. This effect appears to be due to reduced mental effort.
      CONCLUSION: These results suggest that when the representation of uncertainty for
      this spatial task better matches the expert's preferred representation of the
      problem even a nonexpert can show expert-like performance. APPLICATION: These
      results could apply to any domain where performance requires working with highly
      uncertain information.

PMID- 24930173
TI  - Effects of line length, line spacing, and line number on proofreading performance
      and scrolling of Chinese text.
AB  - OBJECTIVE: The main purpose of this study was to investigate the effects and
      interactions of line length, line number, and line spacing on Chinese screen
      based proofreading performance and amount of scrolling. BACKGROUND: Proofreading
      is an important process, and much of it is now done on screen. The Chinese
      language is increasingly important, but very little work has been done on the
      factors that affect proofreading performance for Chinese passages. METHOD: Three
      display factors related to screen size, namely line length, line number, and line
      spacing, were selected to be investigated in an experiment to determine their
      effects on proofreading performance and amount of scrolling. Correlations between
      proofreading performance in time and accuracy and scrolling amount were also
      analyzed. RESULTS: The results showed that line number and line spacing had
      significant main and interaction effects on both proofreading time and detection
      rate. Line length and line number influenced scrolling amount significantly, but
      there was no interaction effect for scrolling. Scrolling amount was negatively
      correlated with proofreading time and typo detection rate such that more
      scrolling movement was associated with faster proofreading, but lower detection
      rate. There was a trade-off between time and accuracy. CONCLUSION: For balancing
      time and detection rate and improving performance for on-screen Chinese
      proofreading, the display setting of medium line length (36 characters per line)
      with four lines and 1.5 line spacing should be used. APPLICATION: The findings
      provide information and recommendations for display factors and the screen design
      that should prove useful for improving proofreading time and accuracy.

PMID- 24930174
TI  - Perceptual grouping effects on cursor movement expectations.
AB  - OBJECTIVE: Two studies were conducted to develop an understanding of factors that
      drive user expectations when navigating between discrete elements on a display
      via a limited degree-of-freedom cursor control device. BACKGROUND: For the Orion
      Crew Exploration Vehicle spacecraft, a free-floating cursor with a graphical user
      interface (GUI) would require an unachievable level of accuracy due to expected
      acceleration and vibration conditions during dynamic phases of flight. Therefore,
      Orion program proposed using a "caged" cursor to "jump" from one controllable
      element (node) on the GUI to another. However, nodes are not likely to be
      arranged on a rectilinear grid, and so movements between nodes are not obvious.
      METHOD: Proximity between nodes, direction of nodes relative to each other, and
      context features may all contribute to user cursor movement expectations. In an
      initial study, we examined user expectations based on the nodes themselves. In a
      second study, we examined the effect of context features on user expectations.
      RESULTS: The studies established that perceptual grouping effects influence
      expectations to varying degrees. Based on these results, a simple rule set was
      developed to support users in building a straightforward mental model that
      closely matches their natural expectations for cursor movement. CONCLUSION: The
      results will help designers of display formats take advantage of the natural
      context-driven cursor movement expectations of users to reduce navigation errors,
      increase usability, and decrease access time. APPLICATION: The rules set and
      guidelines tie theory to practice and can be applied in environments where
      vibration or acceleration are significant, including spacecraft, aircraft, and
      automobiles.

PMID- 24930175
TI  - The effects of human finger and Chinese character on Chinese handwriting
      performance on mobile touch devices.
AB  - OBJECTIVE: The aim of the present study is to investigate Chinese handwriting on
      mobile touch devices, considering the effects of three characteristics of the
      human finger (type, length, and width) and three characteristics of Chinese
      characters (direction of the first stroke, number of strokes, and structure).
      BACKGROUND: Due to the popularity of touch devices in recent years, finger input
      for Chinese characters has attracted more attention from both industry and
      academia. However, previous studies have no systematical consideration on the
      effects of human finger and Chinese characters on Chinese handwriting
      performance. METHOD: An experiment was reported in this article to illustrate the
      effects of the human finger and Chinese characters on the Chinese handwriting
      performance (i.e., input time, accuracy, number of protruding strokes, mental
      workload, satisfaction, and physical fatigue). RESULTS: The experiment results
      indicated that all six factors have significant effects on Chinese handwriting
      performance, especially on the input time, accuracy, and number of protruding
      strokes. CONCLUSION: Finger type, finger length, finger width, direction of the
      first stroke, number of strokes, and character structures are significantly
      influencing Chinese handwriting performance. These factors should be taken into
      more consideration in future research and the practical design for Chinese
      handwriting systems.

PMID- 24930176
TI  - Evaluation of a configural vital signs display for intensive care unit nurses.
AB  - OBJECTIVE: The objective was to evaluate a configural vital signs (CVS) display
      designed to support rapid detection and identification of physiological
      deterioration by graphically presenting patient vital signs data. BACKGROUND:
      Current display technology in the intensive care unit (ICU) is not optimized for
      fast recognition and identification of physiological changes in patients. To
      support nurses more effectively, graphical or configural vital signs displays
      need to be developed and evaluated. METHOD: A CVS display was developed based on
      findings from studies of the cognitive work of ICU nurses during patient
      monitoring. A total of 42 ICU nurses interpreted data presented either in a
      traditional, numerical format (n = 21) or on the CVS display (n = 21). Response
      time and accuracy in clinical data interpretation (i.e., identification of
      patient status) were assessed across four scenarios. RESULTS: Data interpretation
      speed and accuracy improved significantly in the CVS display condition; for
      example, in one scenario nurses required only half of the time for data
      interpretation and showed up to 1.9 times higher accuracy in identifying the
      patient state compared to the numerical display condition. CONCLUSION: Providing
      patient information in a configural display with readily visible trends and data
      variability can improve the speed and accuracy of data interpretation by ICU
      nurses. APPLICATION: Although many studies, including this one, support the use
      of configural displays, the vast majority of ICU monitoring displays still
      present clinical data in numerical format. The introduction of configural
      displays in clinical monitoring has potential to improve patient safety.

PMID- 24930177
TI  - Box shape influences the size-weight illusion during individual and team lifting.
AB  - OBJECTIVE: The effects of box shape--specifically width and height--on the
      perception of heaviness were evaluated during individual and team lifting.
      BACKGROUND: Large objects are perceived to be as much as 50% lighter than smaller
      objects with the same mass. This size-weight illusion presents an obvious risk
      when lifting large and heavy boxes. Recent research has shown that shape
      influences this illusion. Specifically, increases in length and width do not
      produce identical decreases in perceived heaviness. However, this effect has been
      documented only in individual lifting, mostly with small objects. METHOD:
      Individuals and teams lifted large boxes and reported their perceptions of
      heaviness. The mass, height, and width of the boxes were varied independently to
      determine their unique effects on perceived heaviness. RESULTS: For both types of
      lift, increasing width produced a greater mean illusory drop (expressed as a
      percentage decrease with 95% confidence intervals) in perceived heaviness (24 +/-
      7% during individual lifting and 41 +/- 8% during team lifting) than increasing
      height (15 +/- 7% during individual lifting and 18 +/- 8% during team lifting).
      CONCLUSION: Size and shape are important factors in perceiving the heaviness of
      boxes during both individual and team lifting. APPLICATION: To avoid
      misperceiving weight and risking injury, lifters should be careful when
      approaching larger (especially wider) boxes.

PMID- 24930178
TI  - The effects of visual and cognitive distractions on operational and tactical
      driving behaviors.
AB  - OBJECTIVE: This study tested the effects of two fundamental forms of distraction,
      including visual-manual and cognitive-audio distraction, with comparison under
      both operational and tactical driving. Strategic control remains for future
      study. BACKGROUND: Driving is a complex control task involving operational,
      tactical, and strategic control. Although operational control, such as lead-car
      following, has been studied, the influence of in-vehicle distractions on higher
      levels of control, including tactical and strategic, remains unclear. METHOD: Two
      secondary tasks were designed to independently represent visual-manual and
      cognitive-audio distractions, based on multiple resource theory. Drivers
      performed operational vehicle control maneuvers (lead-car following) or tactical
      control maneuvers (passing) along with the distraction tasks in a driving
      simulator. Response measures included driving performance and visual behavior.
      RESULTS: Results revealed drivers' ability to accommodate either visual or
      cognitive distractions in following tasks but not in passing. The simultaneous
      distraction condition led to the greatest decrement in performance. CONCLUSION:
      Findings support the need to assess the impacts of in-vehicle distraction on
      different levels of driving control. Future study should investigate driver
      distraction under strategic control.

PMID- 24930179
TI  - The effects of prism adaptation on egocentric metric distance estimation.
AB  - OBJECTIVE: The present experiment evaluated whether training involving throwing
      transferred to metric distance estimation (i.e., describing in feet and inches
      the distance between oneself and targets). BACKGROUND: In prior work, we found
      that metric estimation training negatively transferred to throwing. We explained
      our results in terms of cognitive intrusion. The present study tested that
      possibility by swapping our training and transfer tasks. METHOD: During
      pretesting, participants verbally estimated the metric distances between
      themselves and targets, or they threw a beanbag to targets. During training,
      participants donned goggles that distorted their vision. While wearing the
      goggles, they threw a beanbag to targets. Half received feedback. During
      posttesting, participants removed the distorting goggles and completed the same
      task that they performed during pretesting. RESULTS: The results indicated that
      the distorting goggles degraded throwing at the beginning of training, visual
      feedback improved throwing during training, the effects of training with feedback
      persisted into the throwing posttest, and the effects of training with feedback
      did not transfer to the verbal metric estimation posttest. CONCLUSION: Training
      involving throwing was effective, but did not transfer to verbal metric distance
      estimation. This supports our argument that the negative transfer observed in our
      previous study stemmed from cognitive intrusion. APPLICATION: The present
      experiment suggests that the creation of distance estimation training should
      begin with a careful analysis of the transfer task, and that distance estimation
      training programs should explicitly teach trainees that their training will not
      generalize to all distance estimation tasks.

PMID- 24930180
TI  - Equipment and skills shortage in Uzbekistan.
AB  - In this article, supplied with the help of the International Federation of
      Hospital Engineering (IFHE), five co-authors from the Deutsche Gesellschaft fur
      Internationale Zusammenarbeit (GIZ)--a German organisation that seeks to
      encourage and co-ordinate international cooperation in areas ranging from
      sustainable development to fund management, and its partner organisation, IFHE
      member, the Republican Research Center of Emergency Medicine (RRCEM) in
      Uzbekistan, discuss the use of medical technology in the central Asian country.
      They also explain how a GIZ project is helping to boost the number of skilled
      staff, improve quality assurance and management in procurement, logistics, and
      maintenance, and promote good training of medical and technical staff, across
      Uzbekistan.

PMID- 24930181
TI  - 'Self-funding project' for four-site campus.
AB  - In an article which first appeared in Canadian Healthcare Facilities, the monthly
      magazine of the Canadian Healthcare Engineering Society (CHES), Michelle
      O'Brodovich and Etienne deMuelenaere, of independent, ISO-certified, energy
      efficiency specialist, Ecosystem (which has offices across the U.S. and Canada),
      describe a wide-ranging energy conservation programme, involving 29 different
      measures at four hospital sites, currently being implemented for Lakeridge Health
      in Ontario, Canada.

PMID- 24930182
TI  - Preparing the MGPS operational policy.
AB  - Three articles that featured in HEJ's April and November 2013, and April 2014
      issues, focused, respectively, on the roles and responsibilities of those
      operating and managing medical gas pipeline systems, the MGPS Permit to Work
      System, and how to raise and complete the MGPS Permit to Work. In this fourth and
      final part of this 'series' of medical-gas system-related guidance articles by
      the same author, experienced medical gas systems trainer, Geoff Dillow, explains
      how to prepare, implement, monitor, and review, the MGPS Operational Policy.

PMID- 24930183
TI  - Poor commissioning discussed in depth.
AB  - Last October's Healthcare Estates 2013 conference saw one of the first day's
      'Engineering' sessions debate the topic, 'Why do so many buildings disappoint
      their owners and occupants?' Much of the discussion centered on the problems
      caused by 'inadequate management of the commissioning process'. A roundtable
      debate jointly staged recently in London by IHEEM and the B&ES, the leading U.K.
      trade association for building services engineering contractors, took the debate
      forward. As HEJ editor, Jonathan Baillie reports, the discussions confirmed that
      one of the key contributors to poor commissioning is a failure to involve
      specialist building services contractors sufficiently early. It was also agreed
      that finding a really effective 'client-side' project manager, with the panoply
      of skills and experience the role requires, can be 'a tough ask'. In this issue
      of HEJ we report on the debate's first 'half'; in June's edition, we will cover
      'part two' of a lively, forthright, and positive debate.

PMID- 24930184
TI  - Examining 'risks' of overspecifying TMVs.
AB  - Dr. Tom Makin, a highly experienced microbiologist and former Directorate manager
      at the Department of Medical Microbiology at the Royal Liverpool University
      Hospital, and Ken Tench, compliance manager, Estates and Facilities Directorate,
      at Central Manchester University Hospitals NHS Foundation Trust, who has worked
      in operational estate functions since 1984, examine the widespread use of
      thermostatic mixing valves, or TMVs, in healthcare premises. They argue that such
      devices have, in recent years especially, been overspecified, particularly given
      the potential for increased contamination of the outlets, and the resulting
      heightened risk of spread of potentially life-threatening nosocomial waterborne
      diseases.

PMID- 24930185
TI  - Buildings' integral role in good health.
AB  - As reported in last month's HEJ, the new Sustainable Development Strategy for the
      Health, Public Health and Social Care System for 2014-20 rightly emphasises the
      importance of the built environment to health and well-being. Chris Hall, the
      BRE's health sector lead, says this message 'stretches far beyond hospitals and
      healthcare buildings into the communities and homes that people live in'. Here he
      highlights some of the key elements relating to the current carbon efficiency of
      healthcare buildings, considers the impact of 'good' housing on health and
      preventing illness, and looks forward to a series of joint IHEEM and BRE
      'Building Sustainable Development' mini-conference events planned in the run-up
      to October's Healthcare Estates 2014 event in response to the new Strategy,
      designed to share ideas and good practice on sustainable estates issues. The
      first takes place in London later this month (see panel below).

PMID- 24930186
TI  - International theme for seaside event.
AB  - The organisers of this month's HefmA 2014 annual conference and exhibition
      promise delegates "the opportunity to hear international perspectives on the
      current issues facing the worldwide 'family' of health estates and facilities
      professionals". Conference speakers will include a US-based consultant architect
      discussing 'a transformational change programme which has achieved up to
      threefold greater throughput using the existing footprint in a US Emergency
      Department'; the assistant director, Facilities Services, at Health Facilities
      Scotland, focusing on HFS's work to ensure high training standards and succession
      planning, former BBC war correspondent, Kate Adie, describing some of the
      'extraordinary experiences' of an eventful career, and Will Whitehorn, a former
      search-and-rescue helicopter crewman, who later became president of 'the world's
      first commercial spaceline', Virgin Galactic, giving his view on technology's
      impact in business.

PMID- 24930187
TI  - 'Catastrophic impact' for 'the unprepared'.
AB  - Hospitals and other healthcare facilities unprepared for the power cuts predicted
      by energy observers in the light of what they say are insufficient U.K. power
      reserves, and particularly electrical energy capacity, could face 'catastrophic'
      consequences, warns Bill Wright, head of Energy Solutions at the Electrical
      Contractors' Association (ECA). In this opinion piece for HEJ he 'shines a
      spotlight on the consequences of the energy generation problem', and explains how
      electrical contractors can 'deliver the solution'.

PMID- 24930188
TI  - Collaborative project optimises LED lighting.
AB  - Early 2013 saw Brandon Medical, which designs and manufactures equipment ranging
      from operating theatre lighting to medical AV and control systems, celebrate '20
      years of innovation and growth', with a move to a new pounds 2 million, 50,000
      ft2 headquarters in Morley near Leeds, twice the size of its former premises. A
      milestone year then for the entrepreneurial Yorkshire company, but, as HEJ
      editor, Jonathan Baillie, discovered, when he met with joint MD, Graeme Hall,
      2014 should prove an equally exciting one for the medical technology specialist,
      with the launch of several new 'field-leading' medical lighting products designed
      for use in operating theatres and minor examination settings.

PMID- 24930189
TI  - Brunel building will have lasting impact.
AB  - Bathed in natural light from its prominent windows and central glass atrium, the
      new pounds 430 million Brunel Building at Southmead Hospital Bristol features
      what main contractor, Carillion, describes as 'a host of unconventional
      architectural and patient care features, as well as a progressive approach to
      community engagement'. The new building, which is due to admit its first patients
      this month, is also targeted with delivering the country's most sustainable
      construction of its type. Keith Hutton, project director for Carillion, gives
      Health Estate Journal his personal standpoint on this ambitious healthcare
      project.

PMID- 24930190
TI  - Single space transforaminal lumbar interbody fusion in spondylolisthesis: initial
      experience of 30 cases.
AB  - Spondylolisthesis in adults is characterized by the loss of disc height across
      the affected segment with sagital translation. The goal of stabilizing the spine
      is accomplished by fusion. Transforaminal approach for lumbar interbody fusion is
      a very good approach and reduces the complications associated with traditional
      posterior approach. It has been reported to be safe and effective in the
      treatment of spondylolisthesis. It has done to assess the functional outcome of
      Transforaminal Lumbar Interbody Fusion (TLIF) in spondylolisthesis. This
      prospective interventional study was performed from July 2008 to June 2011
      included 30 patients (male 07, female 23), within a age range of 30-59 years.
      Nineteen cases were lytic, 08 cases were degenerative, 02 were post-traumatic and
      01 dysplastic variety of spondylolisthesis. Follow up ranged from 12 to 24 months
      and outcome assessed by VAS and ODI regarding pain and disability. Achievement of
      fusion and complications were documented accordingly. Statistical analysis was
      done by unpaired t-test and chi-squared test in appropriate instances. We
      included twenty One (70.00%) patient had Grade-II Spondylolisthesis and L4 over
      L5 had been the commonest level (53.33%) involved. Pain and disability improved
      significantly and 22 (73.33%) patients returned to their previous level of
      activity. One (03.33%) patient developed superficial wound infection and 01
      (03.33%) had persistent low back pain. All patients had neurological improvement.
      We concluded that Transforaminal Lumbar Interbody Fusion is an effective
      alternative surgical procedure for the treatment of spondylolisthesis. Overall
      outcome is satisfactory in 93.33% cases.

PMID- 24930191
TI  - A comparative study of chemical and immunological method of fecal occult blood
      test in the diagnosis of occult lower gastrointestinal bleeding.
AB  - Fecal occult blood test is the most widely used screening test for diagnosis of
      gastrointestinal bleeding disorders specially colorectal carcinoma. Among the
      various methods of fecal occult blood tests, chemical method is being used
      commonly, but the method has some drawbacks like low participation rate, high
      false positive rate, low sensitivity etc. To overcome these short comings, newer
      immunological method was introduced. This study evaluated the role of
      immunological method of fecal blood test in the diagnosis of occult lower GIT
      bleeding. Stool samples from two hundred patients were examined by both chemical
      and immunological method. The patients who were positive by any or both methods
      of occult blood test, were advised for colonoscopy. During colonoscopy tissues
      were taken for histopathology which was the gold standard of this study. Among
      110 OBT positive patients pathological lesions were detected in 65 patients by
      colonoscopy and histopathology. The diseases detected by colonoscopy and
      histopathology 18 colorectal polyp, 8 colorectal cancer, 24 ulcerative lesions
      and 5 inflammatory bowel disease etc. Regarding comparative analysis of chemical
      and immunological method, the higher sensitivity (95.4% vs. 49.2%), specificity
      (44.4% vs. 37.8%), accuracy (74.5% vs. 44.5%), PPV (71.3% vs. 53.3%) and NPV (87%
      vs. 34%) of immunological method than chemical method was observed. Thus
      immunological method of fecal occult blood test was appeared to be a better
      alternative to conventional chemical method of fecal occult blood test in the
      diagnosis of occult lower GIT bleeding.

PMID- 24930192
TI  - Disseminated intravascular coagulation in acute promyelocytic leukaemia and its
      impact on the induction failure: a single centre study.
AB  - Life-threatening coagulopathy associated with acute promyelocytic leukemia (APL)
      has been the defining clinical characteristic and is an important risk factor for
      fatal haemorrhage and early death. Pathogenesis of coagulopathy in APL is complex
      and mainly includes disseminated intravascular coagulation (DIC). The study was
      done to see the status of DIC and its impact on the outcome of APL in our
      setting. Among the total 60 patients, induction mortality rate was 30% and
      remission rate was 70%. The main cause of induction mortality was bleeding that
      accounts for 66.7% of mortality. DIC was present among 32 out of 60 patients
      (53.33%). Induction mortality has significant relationship to DIC as the
      induction mortality rate is 47% in patients with DIC and 11% in patient without
      DIC (P value 0.0009). Induction motality rate in low, intermediate and high risk
      group is 6.70%, 24% and 58% respectively (p value < 0.0001). Finally, risk group
      subclassification revealed presence of DIC in high risk group has the highest
      early mortality rate.

PMID- 24930193
TI  - Photo-anthropometric study on face among Garo adult females of Bangladesh.
AB  - Facial anthropometry has well-known implications in health-related fields.
      Measurement of human face is used in identification of person in Forensic
      medicine, Plastic surgery, Orthodontics, Archeology, Hair-style design and
      examination of the differences between races and ethnicities. Facial
      anthropometry provides an indication of the variations in facial shape in a
      specified population. Bangladesh harbours many cultures and people of different
      races because of the colonial rules of the past regimes. Standards based on
      ethnic or racial data are desirable because these standards reflect the
      potentially different patterns of craniofacial growth resulting from racial,
      ethnic and sexual differences. In the above context, the present study was
      attempted to establish ethnic specific anthropometric data for the Christian Garo
      adult females of Bangladesh. The study was an observational, cross-sectional and
      primarily descriptive in nature with some analytical components and it was
      carried out with a total number of 100 Christian Garo adult females aged between
      25-45 years. Three vertical facial dimensions such as facial height from
      'trichion' to 'gnathion', nasal length and total vermilion height were measured
      by photographic method. Though these measurements were taken by photographic
      method but they were converted into actual size using one of the physically
      measured variables between two angles of the mouth (chilion to chilion). The data
      were then statistically analyzed by computation to find out its normatic value.
      The study also observed the possible 'correlation' between the facial height from
      'trichion' to 'gnathion' with nasal length and total vermilion height.
      Multiplication factors were estimated for estimating facial height from nasal
      length and total vermilion height. Comparison were made between 'estimated'
      values with the 'measured' values by using't' test. The mean (+/- SD) of nasal
      length and total vermilion height were 4.53 +/- 0.36 cm and 1.63 +/- 0.23 cm
      respectively and the mean (+/- SD) of facial height from 'trichion' to 'gnathion'
      was 16.88 +/- 1.11 cm. Nasal length and total vermilion height showed also a
      significant positive correlation with facial height from 'trichion' to
      'gnathion'. No significant difference was found between the 'measured' and
      'estimated' facial height from 'trichion' to 'gnathion' for nasal length and
      total vermilion height.

PMID- 24930194
TI  - Development and evaluation of an in-house ELISA to detect hepatitis B virus
      surface antigen in resource-limited settings.
AB  - Hepatitis B virus (HBV) infection is of global public health concern. Among
      various serological tests used for the diagnosis and screening of HBV infection,
      the enzyme-linked immunosorbent assay (ELISA) to detect hepatitis B surface
      antigen (HbsAg) is most widely used. The present study was designed to develop
      and standardize a cost effective in-house ELISA for the detection of HbsAg and
      compare its performance with two established commercial kits. The concentrations
      of coating antibody, conjugates and sera were fixed by checkerboard titration.
      Using known HBsAg positive and negative sera, four different concentrations (1,
      0.5, 0.25 and 0.125 microg/well) of coating anti-HBs were applied. Similarly,
      serial dilutions of patients' sera (1 in 2, 1 in 3, 1 in 5 and 1 in 9) and
      conjugates (1 in 2, 1 in 3, 1 in 5, 1 in 9 and 1 in 17) were evaluated by
      checkerboard titration. The optimal concentration of coating antibody was
      determined at 0.25 microg/well and 1 in 9 dilution for both conjugates and sera.
      The performance comparison of our in-house ELISA showed excellent correlation
      with two commercial kits (Pearson 0.957, P = 0.001 for monoclonal antibody coated
      kit and Pearson 0.929, P = 0.000 for polyclonal antibody coated kit) when OD
      values were compared. All commercial kit proven positive samples was positive
      while all negative samples were negative with the in-house ELISA resulting in
      100% sensitivity and specificity. The results of our study demonstrated that our
      in-house ELISA for detection of HBsAg was equally as sensitive and specific as
      two well-known commercial kits. Thus, this system may be a useful tool for
      diagnostic and screening purposes, as well as outbreak investigations.

PMID- 24930195
TI  - A comparative study between fine needle aspiration cytology findings and
      histopathological report of major salivary gland neoplasm in a tertiary hospital
      of Bangladesh.
AB  - Salivary gland tumours are relatively uncommon and most of the tumours arise from
      parotid gland. Fine needle aspiration cytology (FNAC) is advised preoperatively
      as diagnostic tool but sometimes found to shown both false positive and false
      negative results. This study was aimed to find out distribution of neoplasm of
      major salivary glands and also to explore the sensitivity and specificity of
      FNAC. The present cross sectional study was done in the Dept. of Otolaryngology
      Head and Neck Surgery, BSMMU from January 2007 to December 2008. A total number
      of 60 gender-matched patients with major salivary neoplasm, confirmed by FNAC,
      were recruited in the study. Operated salivary gland specimens were sent for
      histopathological examination, histopathological findings were compared. Overall
      male to female ratio was 1:1. Out of 60 cases, 47 (78.3%) patients had parotid
      and 13 (21.7%) patients submandibular gland neoplasm. Male to female ratio for
      parotid tumour was 1:1.1 and for submandibular 1.6:1. Mean age of the patients
      was 44.5 with range of 14-85 years. Of the total 60 cases 47 (78.3%) were benign
      and 13 (21.7%) malignant. Out of 47 parotid tumour 85.1% were benign and 14.9%
      malignant. Among the parotid tumour 97% were superficial lobe and 3.0% deep lobe.
      In case of submandibular gland 53.84% were benign and 46.15% tumour malignant.
      According to the sides of involvement, 25 (53.2%) cases of parotid neoplasm
      tumour were in the left and 22 (46.8%) the right. In submandibular gland the
      distribution was 7 (53.8%) and 6 (46.16%) respectively. Statistically incidence
      of parotid tumour was significantly higher than submandibular tumour (p < 0.05).
      Out of 60 cases in 56 (93.3%) preoperative FNAC and postoperative
      histopathological findings were same. There was 1.7% false positive and 5% were
      false negative results. Sensitivity, specificity of FNAC were 80% and 97.8%
      respectively. Positive predictive value was 92.3% and negative predictive 93.6%
      for FNAC.FNAC though cheap and safe but its diagnostic accuracy was
      93.3%.Histopathologial examination remained to be of value for diagnostic
      confirmation of major salivary gland neoplasm.

PMID- 24930196
TI  - Assessing glomerular filtration rate in healthy adult potential kidney donors in
      Bangladesh: a comparison of various prediction equations with measured glomerular
      filtration rate by diethylentriamine pentaacetic acid renogram.
AB  - To ensure that potential kidney donors in Bangladesh have no renal impairment, it
      is extremely important to have accurate methods for evaluating the glomerular
      filtration rate (GFR). We evaluated the performance of serum creatinine based GFR
      in healthy adult potential kidney donors in Bangladesh to compare GFR determined
      by DTPA with that determined by various prediction equations. In this study GFR
      in 61 healthy adult potential kidney donors were measured with 99mTc
      diethylenetriamine penta-acetic acid (DTPA) renogram. We also estimated GFR using
      a four variable equation modification of diet in renal disease (MDRD), Cockcroft
      Gault creatinine clearance (CGCrCl), Cockcroft-Gault glomerular filtration rate
      (CG-GFR). The mean age of study population was 34.31 +/- 9.46 years and out of
      them 65.6% was male. In this study mean mGFR was 85.4 +/- 14.8. Correlation of
      estimated GFR calculated by CG-CrCl, CG-GFR and MDRD were done with measured GFR
      DTPA using quartile. Kappa values were also estimated which was found to be 0.104
      for (p = 0.151), 0.336 for (p = 0.001) and 0.125 for (p = 0.091) respectively.
      This indicates there is no association between estimated GFR calculated by CG
      CrCl, CG-GFR, MDRD with measured GFR DTPA. These results show poor performance of
      these equations in evaluation of renal function among healthy population and also
      raise question regarding validity of these equations for assessment of renal
      function in chronic kidney disease in our population.

PMID- 24930197
TI  - Role of transvaginal sonography in the detection of endometrial carcinoma.
AB  - Transvagival sonography is superior to transabdominal sonography in most cases of
      pelvic pathology. Objective of this study is to evaluate the clinical usefulness
      of transvaginal ultrasonography (TVS) in pre, peri and post menopausal women
      suspected to have endometrial carcinoma. This cross sectional study was done with
      40 patients who are clinically suspected having thickened endometrium. The study
      was carried out January 2007 to November 2008 for a period of two years. The
      patients having endometrial carcinoma diagnosed by TVS was correlated with
      histopathological diagnosis following collection of the report from the
      respective cases. Of total 40 cases, 2 (5.0%) cases were endometrial carcinoma
      and 38 (95.0%) were negative for endometrial carcinoma respectively in TVS
      findings. On the other hand 3 (7.5%) cases were endometrial carcinoma and 37
      (92.5%) cases were negative for endometrial carcinoma in histopathological
      findings. The validity of TVS in diagnosis of endometrial carcinoma were studied
      by calculating sensitivity, specificity, accuracy, positive predictive value and
      negative predictive value, which were 67 percent, 100 percent, 98 percent, 100
      percent and 97 percent respectively. As the TVS findings of the present study
      correlated well with the histopathology findings and the validity test values
      were higher than observed by others, it can be concluded that TVS is sensitive
      and accurate modality in the evaluation of endometrial carcinoma.

PMID- 24930198
TI  - Detection and estimation of human papillomavirus viral load in patients with
      cervical lesions.
AB  - Human papillomavirus (HPV) high risk genotype infection and HPV viral load
      influences the development of invasive cervical cancer and cervical intra
      epithelial neoplasia (CIN). HPV DNA testing for screening of cervical cancers may
      play a potential role in its early detection and management. The present study
      detected HPV DNA and estimated HPV viral load in different types of cervical
      lesions among Bangladeshi women. Using the Hybrid Capture 2 (HC2) assay, HPV DNA
      was tested among 68 women between 25-70 years of age. A total of 13 (19.1%) cases
      were positive for HPV DNA. The highest viral load (501 x 10(3) copies/ml) was
      detected in a patient with invasive carcinoma, while the lowest viral load (105 x
      10(3) copies/ml) was detected from a case of chronic cervicitis. The mean viral
      load in CIN I was 119.25 x 10(3) +/- 12.5 x 10(3) copies/ml (range: 110 x 10(3) -
      137 x 10(3) ) and 208.50 x 10(3) +/- 0.59 x 10(3) copies/ml (range: 139 x 10(3) -
      305 x 10(3)) in CIN II/III. Interestingly, HPV DNA was detected from a patient
      with normal cytological findings. Our study observed a moderate presence of high
      risk HPV genotypes among women with cervical lesions. The HPV viral load varied
      with the age of the patients and stage of cervical lesions. The HC2 assay is a
      promising tool for diagnosing high-risk HPV infection especially before cytology
      tests show any abnormality.

PMID- 24930199
TI  - Correlation of ultrasonographically determined renal cortical thickness and renal
      length with estimated glomerular filtration rate in chronic kidney disease
      patients.

PMID- 24930200
TI  - Thromboembolism in tuberculosis: a neglected comorbidity.

PMID- 24930201
TI  - Outcome of pulmonary rehabilitation in patients after acute exacerbation of
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is an evidence-based intervention in
      patients with chronic obstructive pulmonary disease (COPD) which improves the
      exercise capacity and quality of life (QoL). METHODS: We studied 60 patients
      after an episode of acute exacerbation of COPD (AECOPD). They were randomised to
      receive conventional treatment without pulmonary rehabilitation (CTWPR) (n=30)
      or, standard treatment plus a 12-week post-exacerbation pulmonary rehabilitation
      (PEPR) programme in addition. Assessment of exercise capacity by six minute walk
      test (6MWT) and QoL measured by St George's Respiratory Questionnaire (SGRQ) were
      carried out initially and at the end of three months. RESULTS: The baseline
      characteristics of both the groups were found to be similar. There was a
      statistically significant increase in the six minute walk distance (6MWD)
      (increase by 37.9 meters, p< 0.001) and a significant decline in the total SGRQ
      score (by 3.8 units p< 0.001) in the PEPR group compared to CTWPR group.
      CONCLUSION: Early pulmonary rehabilitation in patients with an AECOPD has
      significant benefits on the QoL and exercise capacity.

PMID- 24930202
TI  - The effect of a short-term pulmonary rehabilitation on exercise capacity and
      quality of life in patients hospitalised with acute exacerbation of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Recent research shows that pulmonary rehabilitation (PR) programmes
      in patients with acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD), reduced dyspnoea, improved exercise capacity, and prevented occurrence
      of further exacerbations. OBJECTIVE: To evaluate the utility of a 3-week PR
      programme in patients with AECOPD. METHODS: Patients admitted with AECOPD,
      following clinical stabilisation in the respiratroy intensive care unit (RICU),
      were alternately assigned to intervention (n=15); and control groups (n=15),
      respectively. Baseline assessment included spirometry, six-minute walk test
      (6MWT), symptom limited cardiopulmonary exercise test (CPET), health-related
      quality of life (HRQoL) assessment by generic questionnaire medical outcomes
      study short form (S-F 36) questionnaire and dyspnoea evaluation by Borg score.
      The intervention group patients were treated with usual care plus PR exercises in
      the form of 20 minutes each of walking, bicycle ergometry and resistance
      exercises, thrice-weekly for three weeks. The control group patients were treated
      with only the usual care. After discharge from hospital the treatment regimens
      were continued on alternate days on outpatient basis, for a total of three weeks.
      The assessment was repeated in both the groups after three weeks. RESULTS: Nine
      sessions of PR exercises produced statistically significant improvement in
      general well-being, forced expiratory volume in the first second (FEV1), 6MWT
      parameters, exercise capacity, peak oxygen uptake and volume of oxygen
      consumption (VO2)/Watts slope on CPET in patients with AECOPD. CONCLUSION: Short
      duration PR programmes appear to be helpful in the management of AECOPD.

PMID- 24930204
TI  - Applications of ultrasonography in respiratory intensive care.
AB  - Emerging evidence suggests that ultrasonography of lung is a fast, inexpensive,
      widely available bed-side diagnostic tool which is useful for quick and early
      diagnosis of respiratory diseases. It is useful in the differential diagnosis of
      pulmonary infiltrates and has good accuracy in identifying consolidation and
      alveolar-interstitial syndrome. This technique can also be useful in the
      immediate evaluation of patients with dyspnoea or acute respiratory failure in
      the respiratory intensive care unit and helps in monitoring treatment response.
      Ultrasonography of lung has also been found to be useful in the diagnosis of
      pulmonary embolism, traumatic lung contusion and lung consolidation as well.
      There is a need for developing specific guidelines for establishing the standards
      of training and education regarding lung ultrasonography in India.

PMID- 24930203
TI  - Clinical profile of pneumonia and its association with rain wetting in patients
      admitted at a tertiary care institute during pandemic of influenza A (H1N1) pdm09
      virus infection.
AB  - BACKGROUND: Influenza pneumonia often occurs as epidemics in the Asian countries
      and have significant impact on the health of world population. METHODS: We
      studied the association of rain-wetting with occurrence of pneumonia during the
      outbreak of the influenza A (H1N1) pdm09 virus infection. All patients admitted
      with community-acquired pneumonia during the period 13th September to 10th
      October 2010 were recruited in the present study. The diagnosis of influenza was
      established by real-time polymerase chain reaction (RT-PCR). The demographic data
      and clinical profile of the patients were recorded with a special consideration
      to record of possible risk factors. RESULTS: Of the 123 patients studied, 39
      (32%) patients had tested positive for influenza A (H1N1) pdm09; 12 (10%) tested
      positive for influenza A and remaining 72 (58%) patients were negative for
      influenza virus. Pattern of illness was almost identical in H1N1-positive and
      negative groups. History of rain-wetting was present in 48 patients (39%)
      preceding the onset of illness. Getting wet in the rain was significantly higher
      in patients with pneumonia than control subjects [odds ratio 2.53, 95% confidence
      intervals (CI) 1.301-4.91; p=0.009)]. The number of pneumonia patients was also
      higher on rainy days and the numbers started declining a week later. CONCLUSION:
      More pneumonia patients are admitted during the periods of greater rainfall and
      rain-wetting may be an important risk factor for the occurrence of pneumonia.

PMID- 24930205
TI  - Recurrent spontaneous pneumothorax in pregnancy.

PMID- 24930207
TI  - Idiopathic central sleep apnoea: an Indian case with polysomnographic findings.
AB  - Patients with idiopathic central sleep apnoea (ICSA) usually complain of poor
      quality sleep; yet many of them do not receive appropriate treatment because of
      poor recognition of ICSA by health professionals. We report the case of a patient
      with ICSA who was misdiagnosed and received treatment for seizures, depression or
      anxiety for a number of years and discuss the differential diagnosis and
      treatment options for ICSA.

PMID- 24930206
TI  - Thoracoscopic and endovascular management of retained haemothoarx associated with
      an intercostal artery pseudoaneurysm.
AB  - Intercostal artery pseudoaneurysm (IAP) is a rare entity and may complicate a
      percutaneous intervention through an intercostal space or follow thoracic trauma.
      Its rupture into the pleural space can give rise to haemothorax, which if
      untreated may lead to a retained haemothorax (RH). Traditionally both the IAP and
      the RH are managed by a thoracotomy. We report a patient who developed an IAP
      with haemothorax following a trauma. The diagnosis was established by computed
      tomography. The patient was treated by endovascular embolisation of the IAP
      followed by thoracoscopic decortications of the RH.

PMID- 24930208
TI  - Idiopathic pulmonary artery aneursym.
AB  - Idopathic pulmonary artery aneurysm (PAA) is a rare lesion. Clinical experience
      with this condition is limited and current knowledge is mainly derived from
      autopsy findings. We report a patient who came to us with complaints of chest
      pain, breathlessness on exertion and pedal oedema and was diagnosed to have PAA.

PMID- 24930210
TI  - Hair: an unusual foreign body in airways presenting with haemoptysis in an adult
      patient.
AB  - Haemoptysis is defined as expectoration of blood originating from the lungs or
      tracheo-bronchial tree. It is attributed to various causes like tuberculosis,
      bronchiectasis, lung cancer, mycetoma, foreign bodies etc. Various types of
      foreign bodies have been reported in the literature. We report the case of an
      adult female patient who presented with an episode of haemoptysis (150 mL) in
      whom flexible fibreoptic bronchoscopy revealed a single long hair at the carina
      going to left main bronchus. Following successful removal of this hair there were
      no further episodes of haemoptysis and the patient manifested clinical and
      radiological improvement.

PMID- 24930209
TI  - Isolated right pulmonary artery agenesis with agenesis of right upper lobe and
      bronchiectasis of right lower lobe with anomalous arterial supply from celiac
      axis with normal venous drainage.
AB  - Isolated unilateral absence of pulmonary artery (UAPA) is a rare congenital
      anomaly. When detected in infancy, the condition is commonly associated with
      cardiovascular defects which are more frequently associated with left pulmonary
      artery agenesis. Patients with isolated right pulmonary artery agenesis survive
      into adulthood with minimal or no symptoms and are diagnosed incidentally on the
      chest radiographs. We report a case of a 19-year-old female patient who presented
      to us with recurrent haemoptysis. She was symptomatic since the age of four
      years. We report the rare occurrence of UAPA on right side, agenesis of right
      upper lobe and bronchiectasis of right lower lobe with anomalous arterial supply
      of right lung from coeliac axis in this patient.

PMID- 24930211
TI  - [Skin changes in the face. " I have such odd acne around the nose". Perioral
      dermatitis].

PMID- 24930212
TI  - [Entrance via KV branch practice. Family physician with love for home].

PMID- 24930213
TI  - [Change in the career picture. "Female family practice" is still far away].

PMID- 24930214
TI  - [Analysis by subsidiary insurance groups. Too many physician practices are not
      architecturally accessible].

PMID- 24930215
TI  - [The safety of drug therapy. Communication and team work are required].

PMID- 24930216
TI  - [Chronic inflammation does not respond to antibiotics. Is it vasculitis?].

PMID- 24930217
TI  - [How does the fit together? First pain in the joints - then the abdomen].

PMID- 24930218
TI  - [Preventing vitamin D deficiency. Sardines, sun or supplements?].

PMID- 24930219
TI  - [The secret world of the microbiom. Do bacteria make us fat?].

PMID- 24930220
TI  - [Sometimes it is better when the physician knows less].

PMID- 24930221
TI  - [Always measure blood pressure on both upper arms].

PMID- 24930222
TI  - [Risk score for exacerbated COPD].

PMID- 24930223
TI  - [Chilaiditi sign].

PMID- 24930224
TI  - [How to proceed when the pathologist does not confirm suspected Barrett
      esophagus?].

PMID- 24930225
TI  - [When the dog bites, the leech helps out].

PMID- 24930226
TI  - [A lot of gas in the irritable bowel].

PMID- 24930227
TI  - [Mediterranean diet lowers diabetes risk].

PMID- 24930228
TI  - [Recurrent neck pain. CT or MRI scan is not necessary in all cases!].

PMID- 24930229
TI  - [Conservative therapy of cervical pain syndrome].

PMID- 24930230
TI  - [Operative therapy of cervical stenosis].

PMID- 24930231
TI  - [Hyperhidrosis].

PMID- 24930232
TI  - [New aspects in travel vaccinations].

PMID- 24930233
TI  - [Allergic asthma-- what's new?].

PMID- 24930234
TI  - [Polypharmacy].

PMID- 24930235
TI  - [The new headache classification of the International Headache Society].

PMID- 24930236
TI  - [Pruritus on normal non-inflamed skin].

PMID- 24930237
TI  - [Venous ulcer--patience and consequence are demanded].

PMID- 24930238
TI  - [Chronic obstructive lung disease: innovation in differential diagnosis.
      Elimination of alpha 1-antitrypsin deficiency in 15 minutes].

PMID- 24930239
TI  - [Vitamin K antagonists. Long-term therapy optimized by coagulation self
      management].

PMID- 24930240
TI  - [Clarithromycin therapy for patients with cystic fibrosis: a randomized
      controlled trial].

PMID- 24930241
TI  - Alien species of parasites--some questions concerning terminology.
AB  - The article deals with some terms proposed by the proper institutions of the
      Council of Europe for describing the phenomenon of invasion of living organisms
      into new habitats. As these terms were elaborated mainly from the point of view
      of free leaving creatures, the goal of the authors was to discuss the possibility
      to adapt them for parasites species. Several propositions of resolving some
      difficulties have been presented'.

PMID- 24930242
TI  - Helminths in migrating and wintering birds recorded in Poland.
AB  - Among 544 species of helminths recorded in birds on the territory of Poland,
      probably some (17 species of Digenea, 21 Cestoda, 13 Nematoda and 5
      Acanthocephala) do not belong to the native fauna. These are helminths obtained
      in mature stage from birds shortly after their arrival from wintering grounds, or
      from foreign populations wintering with us, or being in the course of spring or
      autumn migration through the area of our country. In general, these helminth
      species have been recorded sporadically in the examined birds.

PMID- 24930243
TI  - Migrations and the introduction of wild ruminants as a source of parasite
      exchange and emergence of new parasitoses.
AB  - The relationship between European bison and cervidae is a good model for studies
      on the influence of migration and introduction of new species on the
      helmhninthofauna of wild ruminants and the occurrence of new parasitoses. Changes
      in the helminthofauna of bison and deer under the influence of changes in the
      environment and living conditions, as well as the introduction and migration of
      other species, are discussed in detail. The exchange of helminths between bison,
      cervids and domestic ruminants is demonstrated. Examples of helminth introduction
      from specific Cervidae species, the formation of the new host-parasite systems
      and the appearance of new parasitoses are also presented.

PMID- 24930244
TI  - Dirofilaria repens Railliet et Henry, 1911--a new parasite acclimatized in
      Poland.
AB  - Dirofilariosis caused by the Dirofilaria repens nematodes is widely dispersed in
      southern Europe, Asia and Africa among dogs, cats, other carnivores and
      occasionally, humans. The first case of D. repens infection, found in Poland in
      2007, concerned humans. In 2009, dirofilariosis was first registered in dogs in 3
      focuses in central Poland, Warsaw, Pruszkow and Zyrardow, whose range grew
      considerably with the subsequent identification of D. repens microfilariae in 119
      dogs in Warsaw and 18 districts of the Mazowieckie Province. The microfilariae of
      D. repens were found in blood samples taken from 1588 dogs from all 16 provinces
      of Poland. D. repens was also recently detected in a mixture of Culex pipiens and
      Aedes vexans mosquitoes collected in Mazowieckie Province using Real Time PCR.
      The results of this study confirms the acclimatisation of D. repens on the
      territory of Poland and a possibility for it to close its life cycle in domestic
      species of mosquito.

PMID- 24930245
TI  - The occurrence of the Dermacentor reticulatus tick--its expansion to new areas
      and possible causes.
AB  - The ornate dog tick (Dermacentor reticulatus) can be found in the temperate zones
      of Eurasia. Its area of occurrence is divided into east and west distributions,
      although the area as a whole is expanding. The initial east-west division was
      most probably associated with the varied climatic profile of Europe, for example,
      the range of specific mean winter and summer temperatures: the region where D.
      reticulatus is absent is characterized by mean winter temperatures between 0
      degree C and 5 degrees C and thin snow cover. The present expansion may be the
      effect of climate change. The mean temperatures in Europe have increased, the
      vegetation season has lengthened and positive trends in the number of wet days
      can be seen. Consequently, northern Europe has become warmer and wetter over the
      last century. Human activity can also influence the spread of D. reticulatus. The
      liquidation of habitats suitable for D. reticulatus and the eradication of their
      hosts can play a role, as can changes in agricultural land use, environmental
      protection and the spread of international tourism and trade. In summary, the
      expansion of D. reticulatus into new areas could be the synergistic effect of
      many favourable factors.

PMID- 24930246
TI  - A biological/medical review of alien tick species (Acari: Ixodida) accidentally
      transferred to Poland.
AB  - Alien tick species of the genera Ixodes, Amblyomma, Hyalomma and Rhipicephalus
      are sporadically transferred to the territories of the Central European
      countries. A biological-medical review of the following alien tick species
      transferred to Poland is presented: Ixodes eldaricus, Ixodes festai, Amblyomma
      sphenodonti, Amblyomma exornatumn, Amblyomma flavomaculatum, Amblyomma latum,
      Amblyomma nuttalli, Amblyomma quadricavum, Amblyomma transversale, Amblyomma
      varanense, Hyalomma aegyptium, Hyalomma marginatum, Rhipicephalus rossicus and
      Rhipicephalus sanguineus. The transfers of tick species out of the areas of
      natural distribution are divided into natural transfers (e.g., migration of ticks
      on hosts) and accidental transfers (e.g., resulting from the transport of
      livestock animals, trade in exotic animals, and transfers on animals during
      travel). It is important to monitor occurrence of unknown tick species on hosts
      in Poland.

PMID- 24930247
TI  - Presence of blood-sucking mesostigmatic mites in rodents and birds kept in pet
      stores in the Cracow area, Poland.
AB  - The aim of the study was to investigate the occurrence of zoonotic arthropod
      parasites in small animals sold in selected pet stores in the Cracow area. The
      research was conducted in seven pet stores, keeping a total of six species of
      rodents and three species of birds. In two shops, two species of mites of the
      order Mesostigmata were detected on the animals and in their surrounding:
      Dermanyssus gallinae, the poultry red mite, and Ornithonyssus bacoti, the rat
      mite. Both observed species of mites may be harmful to animals, as well as to
      people working in the shops or potential pet owners. This study discusses the
      possible origin of the parasites and their importance to human health.

PMID- 24930248
TI  - Herbal formulations as feed additives in the course of rabbit subclinical
      coccidiosis.
AB  - Two simultaneous experiments were carried out in a breeding farm of New Zealand
      White rabbits (Oryctolagus cuniculus f. domesticus) to determine the feasibility
      of replacing coccidiostats with garlic and oregano preparation. The research took
      place during June and July, the period of the greatest threat of coccidiosis
      caused by Eimeria spp. (Apicomplexa: Eimeriidae). In one investigation, 40
      rabbits aged 1-3 months were divided into four groups of ten animals: Group A
      being a control which received no coccidiostats in feed, Group B receiving the
      coccidiostat Baycox in water once at weaning, Group C receiving the coccidiostat
      robenidine in feed, and group D receiving herbal extracts in feed. In the second
      trial, six mated females were allocated equally to three groups analogous to A,
      C, and D above during pregnancy and lactation. Bulk stool samples were collected
      from each group of rabbits at weekly intervals for coproscopic analysis, and the
      production results of the animals were recorded. In the young rabbits, both the
      faecal coccidia oocyst counts and body weight gains were more favourable in group
      D than the remaining groups. Also, the female rabbits of group D were the least
      infected. The results demonstrate that garlic and oregano feed additives exert a
      positive influence on the level and course of coccidia infection, with regard to
      maintaining a good level of animal productivity, and these herbal extracts appear
      to have potential value in coccidiosis prophylaxy.

PMID- 24930249
TI  - (Almost) 'instant orthodontics'.

PMID- 24930250
TI  - Haemostasis. Part 1: The management of post-extraction haemorrhage.
AB  - The management of bleeding complications following a dental extraction is an
      essential skill for the dental practitioner. Extractions are often carried out on
      patients with complex medical histories and a long list of medications. This
      paper aims to help the clinician manage post-extraction haemorrhage. A review of
      the management of patients on anti-thrombotic medications will be covered in a
      subsequent paper. CLINICAL RELEVANCE: This article reviews the management of
      haemorrhage following tooth extraction; from the risk assessment of any
      underlying medical conditions and medications, to the clinical techniques used to
      control bleeding following an extraction.

PMID- 24930251
TI  - Frequently asked questions in direct pulp capping of permanent teeth.
AB  - Direct pulp capping is a proven method of preserving tooth vitality of a mature
      permanent tooth in cases of pulp exposures. The indications for this treatment,
      treatment modalities and materials are discussed in this paper. CLINICAL
      RELEVANCE: This paper answers many of the frequently asked questions by general
      practitioners, dental students and specialists about direct pulp capping.

PMID- 24930252
TI  - Anterior tooth alignment--recommendations for stability.
AB  - This article considers the importance of current orthodontic practice in
      retention and stability when considering anterior tooth alignment. CLINICAL
      RELEVANCE: With the exponential increase of general dentist-based orthodontic
      systems for anterior tooth alignment, with considerably shorter treatment times,
      practical recommendations along with a current literature review are required to
      improve success and outcome of the long-term result.

PMID- 24930253
TI  - Shall I go digital?
AB  - Dental radiographic imaging is slowly transferring to digital format. The
      decision to invest in this new technology should be based on a good understanding
      of the different types of digital imaging available within the dental field. This
      article outlines its use in general dental practice, highlighting the pros and
      cons of the various systems both for intra-oral and extra-oral radiography.
      CLINICAL RELEVANCE: An understanding of the mechanisms of digital imaging and
      their associated potential problems are required by any clinician moving to film
      less imaging.

PMID- 24930254
TI  - Simplified basic periodontal examination (BPE) in children and adolescents: a
      guide for general dental practitioners.
AB  - Dental plaque-induced periodontal diseases are common in children and adults.
      Guidelines were previously not available for the periodontal screening of under
      18s. However, new guidelines have been introduced by the British Society of
      Periodontology and the British Society of Paediatric Dentistry which set out
      recommendations for the periodontal screening and management of under 18s in
      primary dental care. This article provides a practical guide for general dental
      practitioners on how to use the BPE in children and adolescents, and highlights
      the importance of early detection and management of periodontal diseases in this
      age group. A failure to use the modified BPE in a young patient who is later
      diagnosed with periodontitis may leave a dentist vulnerable to a medico-legal
      complaint or claim. CLINICAL RELEVANCE: New BPE guidelines for children and
      adolescents have been introduced by the BSPD and BSP; it is important that all
      dentists are aware of these guidelines and how to implement them in general
      practice.

PMID- 24930255
TI  - The management of risk. Part 3: Recording your way out of trouble.
AB  - Clinical and ethical risk management requires not only the correct treatment
      being provided, and appropriate consent obtained, but also good records of that
      treatment. This third article of the series describes the characteristics of good
      records and their role in helping to prevent the progression of complaints,
      General Dental Council (GDC) cases and legal claims. CLINICAL RELEVANCE: Good
      records are of fundamental importance in managing risk and preventing and
      resolving complaints and legal claims.

PMID- 24930256
TI  - What steroid supplementation is required for a patient with primary adrenal
      insufficiency undergoing a dental procedure?
AB  - Patients with primary adrenal insufficiency (Addison's disease) lack the
      endogenous steroid hormones cortisol and aldosterone and require daily steroid
      therapy (usually hydrocortisone and fludrocortisone) to replace them. These
      patients are unable to adapt physiologically to stress and may need supplemental
      steroid therapy when having dental procedures, to prevent adrenal crisis. This
      paper provides guidance on dental procedures for which steroid supplementation
      may be required in patients with primary adrenal insufficiency and gives advice
      on doses and timing of supplementation. It does not address the management of
      patients with secondary adrenal insufficiency caused by long-term use of high
      doses of steroids. This document is for guidance only. Patients with primary
      adrenal insufficiency should be assessed individually as steroid requirements
      will vary. CLINICAL RELEVANCE: Although patients with primary adrenal
      insufficiency (Addison's disease) are invariably very well informed about their
      steroid requirements prior to a dental procedure, dental staff should have an
      understanding of the steroid supplementation that may be required.

PMID- 24930257
TI  - Quality of life issues in head and neck cancer.
AB  - Head and neck cancer (HNC) constitutes approximately 3% of all cancers in the UK,
      with in excess of 8500 new cases annually. Management of HNC depends on site,
      extent, histology, previous medical history and patient choice. A
      multidisciplinary approach is required to optimize patient wellbeing, owing to
      the significant functional and psychosocial implications that can impact on
      quality of life. Members of the dental team, to include the general dental
      practitioner, have a key role in patient care; therefore the dental team should
      be knowledgeable in the short-term and longer-term implications and how this
      impacts on quality of life. CLINICAL RELEVANCE: This article offers the dental
      team with an overview of how HNC and the various treatments, such as surgery,
      radiotherapy and chemotherapy, impact upon quality of life, both in the short
      term and longer-term.

PMID- 24930258
TI  - Bizarre tooth surface loss and the Miswak stick.
AB  - Tooth surface loss can present in a variety of ways, some of which can appear
      rather strange on first examination. This case report demonstrates an unusual
      presentation of tooth surface loss (TSL) and its subsequent treatment. This loss
      of hard dental tissue appeared to be affecting the whole of the patient's
      remaining dentition, both lingually and buccally. Detailed questioning revealed
      the origins of this problem which turned out to be due to excessive use of an
      intra-oral Miswak chewing stick. Cinical Relevance: This article will enable
      clinicians to understand the importance of specific, targeted history-taking,
      involving a rare case of tooth surface loss as well as the use of minimally
      destructive restoration composites and a fibre-reinforced composite bridge.

PMID- 24930259
TI  - How good are our impressions? An audit of alginate impression quality in the
      production of removable prostheses.
AB  - Impressions are taken regularly in practice giving vital information to the
      dental laboratory, but are there quality assurance systems in place to make sure
      that they are up to a sufficient standard? As dental professionals we have to
      appreciate that dental technicians can only work with the information given to
      them. This makes the skill of taking a good impression vital in order for us as
      clinicians to provide prostheses of good quality. This paper outlines an audit of
      alginate impressions and their quality in the making of removable prostheses.
      CLINICAL RELEVANCE: To record the quality of impression taking, and how one's own
      ability to critique an impression may differ from that of our colleagues.

PMID- 24930260
TI  - Oral medicine: 17. Radiolucencies and radio-opacities. D. Antral disease.

PMID- 24930261
TI  - Dental materials--what goes where? A reply to the current status of glass
      ionomers.

PMID- 24930262
TI  - Author's reply: To PMID 24597029.

PMID- 24930263
TI  - What makes a good dentist? A pilot study.

PMID- 24930264
TI  - How many of our patients can really give consent?--A perspective on the relevance
      of the Mental Capacity Act to dentistry.

PMID- 24930266
TI  - Options for temporization in the aesthetic zone after implant fixture placement.

PMID- 24930267
TI  - The benefits of international university partnerships: the perspectives of a
      Canadian faculty member.

PMID- 24930268
TI  - [Perception of fathers as for their involvement in activities with their
      children].
AB  - This is an exploratory, descriptive study with a quantitative approach and the
      aim to identzfy the perception of fathers regarding their children's needs;
      strategies used by fathers to get closer to their children as well as to analyze
      the influence of household chores and children's education in their fathers'
      lives. Study subjects were 92 men with six-year-old children, residing in the
      city of Rio Grande, state of Rio Grande do Sul (RS). The results revealed fathers
      who are more engaged in activities with their children, valuing confidence,
      safety, as well as proximity to family as children's main needs, having
      prioritized the progress children make as well as attention to listening and
      conversation. Children's education does not aggregate more problems than they
      imagined, managing to plan life the way they seek to. These findings show that,
      in the sample studied, fathers have been able to develop more affectionate
      actions aimed at being more involved with their children.

PMID- 24930269
TI  - [Access to care for women during childbirth in university hospitals:
      characterization and associated factors].
AB  - This study aimed to analyze the socioeconomic, demographic, obstetric, neonatal
      and healthcare factors associated with access to care by women during childbirth.
      It was a transversal study conducted on puerperal women in two university
      hospitals in the state of Parana, Brazil in 2011. Access to childbirth was
      analyzed according to socioeconomic, demographic, obstetric, neonatal and
      healthcare variables. The puerperal women were interviewed during
      hospitalization, in the first 72 hours after birth. The data was analyzed by
      relative frequencies and calculation of the chi2, considering a significant
      association when p < or = 0.05. The overall rate of women referred to university
      hospitals was 17.7%. A significant associated was found between access to
      childbirth and residing in other cities; premature birth; underweight newborns;
      complications in the current pregnancy and the use of ambulances. It was
      concluded that the associated factors found in this study suggest that pregnant
      women with some risk required referral to university hospitals.

PMID- 24930271
TI  - [Young people's conception of HIV/AIDS and the use of condoms in sexual
      intercourse].
AB  - The aim of this study was to gather knowledge regarding the conception of young
      people as for HIV/AIDS and the use of condoms in sexual intercourse. Survey
      conducted in May, 2012, at a public school in the city of Joao Pessoa, Paraiba,
      with eleven young people of both sexes. The chosen technique of investigation was
      a semi-structured interview. Empirical data were organized according to
      categorical content analysis, the following categories emerging: "AIDS: what
      young people think", "AIDS prevention methods" and one subcategory "Trust in the
      partner as a method for HIV/AIDS prevention". As observed, there is knowledge of
      condom use as a preventive method against HIV/AIDS; trust in the partner and
      faithfulness were also cited as preventive methods in both sexes. It is suggested
      that, when investing in national and regional proposals, not only social
      inequalities are to be considered but especially the local realities of different
      young people in different national scenarios.

PMID- 24930270
TI  - [Social support perceived by cancer patients and its relation with social and
      demographic characteristics].
AB  - To analyze the relation between social support and socio-demographic
      characteristics of oncology patients. Transversal study, developed with oncology
      patients living in the Ijut city, Rio Grande do Sul state, Brazil between July
      and December 2012, the population was selected through convenience. For data
      collection we used the Brazilian version of the Social Support Scale and the
      Medical Outcomes Study data were analyzed with descriptive statistics resources
      and analytical. Average scores on the dimensions were: 82.36 +/- 24.42 (positive
      interaction), 85.39 +/- 19.81 (information), 87.98 +/- 18.68 (emotional support),
      88.52 +/- 18.56 (material support) and 93.50 +/- 14.44 (affective support).
      Evidences showed higher averages in male mulattos patients (p < 0.05). There was
      a direct and growing relationship between per capita income, social support and
      affective positive interaction. It was proven that patients receive social
      support in all dimensions, with high scores, but with variations, considering the
      characteristics of gender, civil status, educational level, per capita income and
      race.

PMID- 24930272
TI  - [Intervening conditions on governance of the nursing practice at an obstetrics
      centre].
AB  - Governance refers to all processes that grant nurses autonomy, control and
      authority over the nursing practice. The aim of this study was to identify
      intervening conditions on governance of nursing practice at an obstetrics centre.
      This is a qualitative study based on the grounded theory method. Data were
      collected between January and May 2013 by means of semi-structured interviews
      with 27 participants of a university hospital in southern Brazil, divided into
      four sampling groups. Data were analysed using open, axial and selective coding.
      Governance is reinforced by experience and professional autonomy, coordination of
      the care and management dimension, interpersonal communication, satisfaction and
      engagement with the profession. It is limited by difficulties with interpersonal
      relationships, work overload and precarious physical structure of the maternity
      units. This study provides arguments for the discussion on improvements in
      healthcare and the professional satisfaction of nurses and nursing teams.

PMID- 24930273
TI  - [Occupational stressors among nurses working in urgent and emergency care units].
AB  - The study aimed to assess occupational stressors among nurses working in urgent
      and emergency care facilities. It is a descriptive research developed in two
      public hospitals of different complexity degrees, with 49 nurses. Data were
      collected from June to September 2011. The Bianchi's Stress Scale, which is
      composed of six domains: Relationship, Unit functioning, Staff management,
      Nursing care, Unit coordination, and Work conditions was used to assess
      occupational stressors based on the regular activities performed by nurses. Data
      were analyzed by using descriptive statistics and Mann Whitney-U test. For the
      nurses working in the high complexity healthcare facility - hospital A the most
      stressful domain was Nursing care, while for those professionals working in the
      medium complexity healthcare facility - hospital B, Staff management was the most
      stressful domain. The nurses from hospital A perceived care-related activities as
      more stressful, while for those in hospital B administrative activities were
      considered more stressful.

PMID- 24930274
TI  - [Gestational weight gain and nutritional state of the newborn: a descriptive
      study].
AB  - The objective was to characterize puerperal women in relation to gestational
      weight gain and their newborns in accordance with the nutritional state at birth.
      This is a descriptive, quantitative and retrospective study approved by the
      Ethics Committee at the institution responsible. The collection of data was from
      December 2012 to May 2013. The sample was composed of 24 puerperal women and
      their children. The participants presented an average age of 26.5 (DP=5.4) years,
      79.2% white; 91.7% married; 58.3% multiparous; 75% with a level of education
      between secondary school and higher education; 58.3% with a low family income;
      54.1% presented an altered pre-gestational nutritional state and 75% obtained an
      inadequate gestational weight gain. 79.2% of the newborns were classified as
      Adequate for Gestational Age (AIG). The newborns classified as Large for
      Gestational Age (GIG) were from pregnant women that had excessive weight gain or
      were overweight. It was concluded that health professionals should be attentive
      to nutritional deviations with the intention of avoiding complications for
      maternal/fetal health.

PMID- 24930275
TI  - [Hand hygiene in hospital environments: use of conformity indicators].
AB  - An exploratory descriptive study with a quantitative approach whose objective was
      to use indicators to evaluate the frequency and infrastructure for hand hygiene,
      as well as the nursing team's knowledge about the subject. Systematized
      observation was carried out at hospital in the state of Sao Paulo, Brazil of the
      routine activities of 33 participating professionals (nurses and technicians) as
      well as the application of an individual questionnaire about the subject. 1206
      opportunities for hand hygiene were identified, though it was effected in only
      481 (39.9%) of them. Alcohol solution was not used at any opportunity. The
      infrastructure indicatorfor hand hygiene was close to the ideal value (83.30%).
      The professionals reported a high frequency of hand hygiene, demonstrating
      knowledge in relation to its importance, yet contradicting the findings of the
      observation. It was concluded that, despite the adequate infrastructure, hand
      hygiene was below that expected, requiring actions and strategies to overcomes
      these barrier and increase the use of alcohol solution.

PMID- 24930276
TI  - [Impact of vaccination in the reduction of hepatitis B in Parana].
AB  - This study identified the impact of hepatitis B vaccine over reducing incidence
      of this disease in Parana State, between 2001 and 2011, and discussed the role of
      nursing in immunization. Descriptive documental and quantitative research.
      Utilized secondary data of hepatitis B, between 2001 and 2011 and vaccination
      coverage of hepatitis B vaccine between 1995 and 2011 in Parana State, available
      in DATASUS, SINAN and Immunization Programs. Data has been collectedfrom May to
      July 2012. Included cases of hepatitis B confirmed by laboratory testing. Of the
      14,434 selected cases, 81.8% was in urban residents, 86.5% belonged to 20 to 59
      age group and 45.3% were infected by sexual transmission. In the correlation of
      vaccine coverage with the incidence, was identified reducing this rate in the
      range of 0 to 9 years old, in places with vaccination coverage's above 95%. It
      concludes that hepatitis B vaccination had impact over disease reduction in
      Parana State.

PMID- 24930277
TI  - [Process of training and insertion in the labor market: a vision of nursing
      graduates].
AB  - Study to analyze nursing graduates' perception about the contribution of the
      training process in its insertion in the labour market. Descriptive exploratory
      study, a qualitative approach. The data was collected in 2011 through
      semistructured interviews. Attended by 15 professionals, graduated from the
      Nursing Course at a South Brazilian university in 2009-2010, inserted in the
      labour market. Data was analysed according to Minayo's proposals. From this
      analysis emerged the category Training route, including the subcategory:
      following the travel itineray. The results demonstrate the need for curricular
      integration, better use of clinical practices experiences, research valorization,
      and the importance of training based on dialogue between students and professors.

PMID- 24930278
TI  - [Nursing students and mental health education in primary care].
AB  - The University of Sao Paulo School of Nursing (EEUSP) went through a period of
      transition from undergraduate syllabus between the years 2009 and 2010. This
      change was made to integrate basic and clinical cycles and to reduce
      fragmentation of the disciplines. The mental health nursing education was
      included in many modules including the primary care. This qualitative study aimed
      to identify how the service offered to people with mental illness was performed
      by 20 undergraduate students in the context of primary care and how they were
      prepared. Data collection was conducted through semi-structured interviews, in
      August 2012, in EEUSP After thematic analysis, we separated in categories:
      Teaching-learning process, Basic Health Unit and Mental health-illness process.
      The socially constructed conception of madness added to the problems related to
      academic training may result in lack of preparation in nursing mental health
      care.

PMID- 24930279
TI  - [Nursing students' perception of the learning process in a hospital setting].
AB  - The aim of this study was to identijf how nursing students perceive and
      experience the learning process during curricular practice in a hospital setting.
      A qualitative, retrospective, documentary study was developed in an undergraduate
      nursing course. Data were comprised of 162 posts made by 34 students in the
      online discussion forum of the Learning Management System Moodle, during the
      first half of 2011. The following themes emergedfrom t he thematic content
      analysis: "nursing students' understanding about the professional practice," and
      "the teaching and learning process in the perspective of nursing students." The
      study demonstrated that the forum was a place for reporting experiences such as
      the description of the physical area, performing procedures, perception of
      nursing care activities, conJlicts with peers, coping with death and learning
      evaluation. The online discussion forum needs to be used by professors as a space
      of interaction so as to contribute to professional training.

PMID- 24930280
TI  - [Profile of patients seen at an outpatient hypertension facility: are there
      gender differences?].
AB  - The objective of this study was to find out whether there are gender dierences
      regarding socio-demographic characteristics and associated risk factors in adults
      monitored in an outpatient hypertension facility. Retrospective analysis of
      records of patients seen at the outpatient hypertension clinic in 2009-2010, in a
      hospital specialized in cardiology, in southern Brazil. All patients were
      beneficiaries from the Brazilian Unified Healthcare System (SUS). The variables
      considered were socio-demographicprofile, anthropometric measurements and risk
      factors for hypertension. For statistical analysis, a signficance level of 5% (p
      < 0.05) was adopted. Of the 209 patient records assessed most belonged to female
      patients (66%), 65.9% of them were married 71.6% were white, with mean age 53.5
      +/- 13.8 years, and 70.1% had a sedentary behavior Regarding risk factors, waist
      circumference and alcohol use were higher among men (p = 0.04). It was concluded
      that there was no gender difference concerning the assessed variables, except for
      the use of alcohol.

PMID- 24930281
TI  - [Planning nursing care in oncology: study of the structure of social
      representations of nurses].
AB  - Characterize the social representations of nurses regarding the planning of
      nursing care for people with cancer, by determining the central nucleus and of
      the peripheral system. Qualitative study conducted in a specialized hospital in
      Salvador, Bahia, between July 2008 and March 2009. Data collection was made by
      free association of words, with forty-one nurses. The data were processed by the
      software Ensemble de Programmes Permettant L'analyse des Evocations and analyzed
      according to the Theory of Social Representations. The results indicated the
      following central elements: humanization, care, organization, individualizing and
      suffering. In the peripheral system, professional and personal attitudinal
      elements necessary for the planning were observed: skill, knowledge on the
      disease, family care, respect and sensitivity. It is concluded that care planning
      is linked to the peculiarities of the individual with cancer, and requires that
      nurses have knowledge and skills necessary to prioritize actions and ensure the
      quality of care.

PMID- 24930282
TI  - [Quality of life and living conditions from the viewpoint of residents in a
      seniors condominium].
AB  - The aim of the study was to understand how residents of a condominium Aging
      realize the quality and conditions of life in this new housing modality. This is
      an exploratory qualitative study of 20 elderly residents of the condominium
      Maringa. Data were collected in February 2012 in the household were
      semistructured and subjected to content analysis interviews. The results indicate
      the factors valued by the elderly in their perception of quality of life such as
      independence, autonomy, having an occupation, developing leisure and acceptance
      of the aging process activities. Also valued the structure and characteristics of
      this housing method due to the possibility of social interaction. We conclude
      that the identification of these aspects allows the planning of strategies for
      integrated care for the elderly and it is suggested that nurses recognize and
      value the aspects highlighted in the planning of care with elderly people in
      general.

PMID- 24930283
TI  - [Time for cleaning and room preparation: connection between surgery size and
      professional perspectives].
AB  - The objective was to verify the association between time needed for room cleaning
      (TLPS) and the surgery size, and related advantages and difficulties faced by the
      circulator of the room asszgned to this task. A mixed method, with a transverse
      quantitative, retrospective approach, using a sample of 3095 surgeries
      performed,from January to June 2011, and a qualitative approach using a Thematic
      Content Analysis of statements from 11 circulators, was used. The average TLPS
      was smaller in size 1 surgeries, increasing in sizes 2, 3 and 4, with a
      significant difference. Advantages reported included organization and size of
      staff and difficulties reported related to sharp, bladed materials mixed with
      surgical instruments and a reduced number of cleaning professionals. The larger
      the size, the higher the TLPS. Surgical teams operating in the Surgical Center
      interfere directly in the process, facilitating or hindering the achievement of
      institutional goals related to quality and productivity.

PMID- 24930284
TI  - [Matrix support work: difficulties in the scope of basic healthcare].
AB  - Qualitative research under the analysis of contents, thematic modality, aimed to
      identify the difficulties lived by the matricial supporter in its practice in the
      Primary Health Care. The scenery of the study were six units of family health
      located in one of the five Sanitary Districts of Joao Pessoa-PB. The data
      collection was performed from August to September 2010, through semi directed
      interviews, in which ten professionals who worked as matricial supporters
      participated. According to the speeches the difficulties faced relate to the
      ignorance of some professionals of the health team toward the function of the
      matricial supporter in the Basic Health Attention; lack of autonomy and
      administrative overload. In this sense, it is suggested that a process of
      reflection about the work of the matricial supporter with the health team aiming
      to acknowledge which contribution of this professional in the reorganization of
      the work of the team of basic attention.

PMID- 24930285
TI  - [Validation of the comprehensiveness of an instrument on ethical problems in
      primary care].
AB  - The study aimed to validate the comprehensiveness of an instrument on the
      occurrence of ethical problems in primary health care and discuss their results.
      This is a methodological research. The technique used was Delphi, which seeks to
      obtain a consensus on a subject by experts, using structured questionnaires that
      are modified to obtain consensus on the comprehensibility of content. The sample
      was composed by nine professionals with expertise in primary health care in Sao
      Leopoldo. Data collection was in March and April 2011. In the first round, the
      professional was asked to respond whether the described situation has represented
      an ethical problem, whether the statement was clear and whether there was any
      suggestion to rewriting the problem. Were presented thirty-six statements, and to
      twenty was suggested new rewrite. After the review and systematization the
      proposed amendments, has begun the second round to seek consensus among all the
      statements that its writing had changed. In the second round, the consensus
      required by the method was obtained. Using the method supported significantly to
      build the instrument in its initial stage, what makes it appropriated and
      comprehensive for the subsequent steps of the validation.

PMID- 24930286
TI  - [Home childbirth: progress or retrocession?].
AB  - Giving birth at home represents a rising modality of delivery care in the
      Brazilian society, although in unrepresentative proportion when compared to the
      number of hospital childbirths. In Brazil, the topic has been broadly discussed
      by different professional categories, highlighting the safety issue involved in
      the process. The aim of this theoretical and reflective study was to present a
      brief overview of the overall care related to home childbirth, also questioning
      the reality of the contemporary Brazilian obstetric scenario. The scientific
      literature presents both obstetric and neonatal outcomes as favorable to home
      childbirth; similar risks when compared to hospital childbirth and higher rates
      of maternal satisfaction, and these both factors justify its practice. Therefore,
      a movement of women who are deeply unhappy with the current model of obstetric
      care is currently observed and they have been opting for home childbirth as a
      response to institutional violence,fragmentation and depersonalization of
      hospital care.

PMID- 24930287
TI  - [The educational practice of preceptors in healthcare residencies: a study on
      reflective practice].
AB  - The purpose of this article was to reflect on thepractice of preceptorship as an
      educational practice in the training and qualifications of professional health
      information for the public health system. This is a theoretical reflection with
      support in the literature. The teacher addresses the teaching-learning process
      and transforms the activities in the work on educational moments. In this area
      arise questions about what is being preceptor and their role in health education.
      It is necessary to teach knowledge beyond the content of the discipline, and
      reflecting about preceptorship as an educational practice in the workplace, the
      preceptor needs pedagogical preparation. Herewith, being a preceptor means being
      a teacher? This reflection places us in front of a problem present in our daily
      exercise, which is the pedagogical training of those who teach for a
      transformation of practice in health.

PMID- 24930288
TI  - [After cross-country motorcycle racing. Traumatic dislocation of thoracic
      vertebrae].

PMID- 24930289
TI  - [Aichach Center of General Medicine. 4-day week thanks to cooperation].

PMID- 24930290
TI  - [How can verbal consultations be calculated according to GOA?].

PMID- 24930291
TI  - [Advantages of the new family practitioner EBM. Fee schedules are camouflage
      hoods for your performance].

PMID- 24930292
TI  - [Blood glucose determination. Nothing but aggravation with the new glucose
      tubes].

PMID- 24930293
TI  - [Physician assisted suicide: medical law and ethics in rare harmony. Hastening
      the parting - may the physician do this?].

PMID- 24930294
TI  - [Patient rights law. This you should know!].

PMID- 24930296
TI  - [Naturopathy consultation. Onset of a common cold: what helps? (interview by
      Brigitte Moreano)].

PMID- 24930295
TI  - [Fear of heights? Acrophobia can be overcome (interview by Dr. Christine
      Starostzik)].

PMID- 24930297
TI  - [When should a patient consult a nephrologist? The proteins are important].

PMID- 24930298
TI  - [Acute cholecystitis. Better chances thanks to early operation].

PMID- 24930299
TI  - [Uncomplicated cystitis in the woman. The clinical picture is the best
      indicator].

PMID- 24930300
TI  - [The number of community acquired infections rises. MRSA: risk from waste
      slurry].

PMID- 24930301
TI  - [Joint prostheses protect against cardiovascular complications].

PMID- 24930302
TI  - [Physician intuition is superior to risk calculation].

PMID- 24930303
TI  - [When the mother sings and speaks, premature infants show better development].

PMID- 24930304
TI  - [Acute blood pressure decrease in stroke has no advantage].

PMID- 24930305
TI  - [Regular breakfast lowers cardiovascular risk].

PMID- 24930306
TI  - [Lifestyle changes body and mind].

PMID- 24930307
TI  - [Diet and mental disorders].

PMID- 24930308
TI  - [Physical activity in mental disorders].

PMID- 24930309
TI  - [Acute exacerbation of COPD].

PMID- 24930310
TI  - [After-care in general practice after lower intestinal resection].

PMID- 24930311
TI  - [Health and longevity by one tablet daily. Fiction and hard facts on the
      polypill].

PMID- 24930312
TI  - [Environmental factors in the pathogenesis of diabetes mellitus].

PMID- 24930313
TI  - [Rhinitis and rhinosinusitis. Phytotherapy: avoiding resistance].

PMID- 24930314
TI  - [The vertigo challenge. The pathway to correct diagnosis].

PMID- 24930315
TI  - [Strontium ranelate. Long-term control of fractures over 10 years].

PMID- 24930316
TI  - [Cancer through the handling of biological agents].
AB  - In March 2012, the International Agency for Research on Cancer (IARC), an agency
      of the World Health Organization (WHO) issued a list. It lists 108 agents for
      which there is sufficient evidence of a carcinogenic effect in humans, depending
      on the cancer site. The vast majority of these actions can take place in the
      workplace. What is new in the list, in addition to the long-known cancer-causing
      chemical and physical agents now biomaterials have been added, such as hepatitis
      B virus, hepatitis C virus, Human papilloma virus, Helicobacter pylori. This
      paper gives an overview on the basis of identifying carcinogenic agents and can
      be displayed in certain cancer site and occupational exposure occupational
      diseases according to the occupational disease regulation.

PMID- 24930317
TI  - [Insulin degludec--a new basal insulin for the treatment of type 1 and type 2
      diabetes].
AB  - After subcutaneous injection, IDeg self-associates to form multihexamer chains
      that slowly dissociate into monomers. This results in a duration of action of
      more than 42 hours as well as a smooth level action profile with low intra
      individual variability. Pharmacokinetic studies foun IDeg to have a half-life of
      approximately 25 hours which is considerably longer than that from other current
      insulin formulations. Based on these properties, IDeg demonstrated low risk for
      nocturnal hypoglycaemic events in the clinical study program. Concurrently, phase
      3 studies have provided evidence for a non-inferior glucose lowering effect when
      compared to other currently available basal insulin formulations. Moreover, the
      long duration of action suggests a flexible handling which could be better
      adapted to patients' needs in daily routine. This article gives an overview of
      the mechanism of action of IDeg and the latest results from phase 2 and phase 3
      studies.

PMID- 24930318
TI  - [Differential diagnosis and treatment of cramps].
AB  - Cramps are painful sensations caused by intense involuntary contractions of
      skeletal muscles, mostly in the calves, usually lasting from a few seconds to
      several minutes. Although cramps are mostly idiopathic, theycan bea symptom of
      other forms of myalgia, restless legs syndrome or spasticity. Especially
      nocturnal cramps can cause considerable distress for patients requiring fast pain
      reduction and effective prophylaxis. Stretching the calf muscles helps preventing
      nocturnal cramps. Pharmacological treatment of leg cramps includes magnesium and
      quinine.

PMID- 24930319
TI  - [Long-term treatment of chronic pain with low-dose 7-day buprenorphine
      transdermal patch. Observational data from elderly patients of pain relief and
      quality of life].
AB  - BACKGROUND: Six-months analysis of non-interventionally collected observation
      data of effectiveness of long-term treatment with low-dose 7-day buprenorphine
      transdermal patch in elderly patients with chronic pain. METHODS: Analysis of
      data regarding pain intensity, pain-related impairments of daily life and quality
      of life documented by 321 pain patients in German primary care (age 72.4 +/- 13.8
      years; 67.3% female; musculoskeletal pain 85.4%; mean pain intensity 6.1 +/- 1.2,
      for 90% > or = 5 NRS11) using standardised self-report instruments (German Pain
      Questionnaire/German Pain Diary). RESULTS: After initiation with 5/10 microg/h
      buprenorphine (89.7%/10.3%), treatment was maintained in 57.1/39.1/3.8% patients
      with stable doses of 5/10/20 microg/h after 6 months. The average pain intensity
      decreased by 5.1 +/- 1.0 (absolute) to 1.0 +/- 1.0 NRS11 (83.5%), pain-related
      impairments and burden of pain were reduced by 86.0% and 87.9%, respectively, and
      pain-related quality of life improved by 97.3% to nearly normalvalues.
      CONCLUSIONS: Pain treatment of elderly persons with 7-day low-dose transdermal
      buprenorphine patch on a stable dose regimen resulted in fast, effective and
      sustained pain relief accompanied by marked improvements in daily life
      participation and quality of life.

PMID- 24930320
TI  - [Recreational athletes and doping--a survey in 11 gyms in the area of
      Frankfurt/Main].
AB  - BACKGROUND: Doping no longer concerns exclusively competitive sports, but also
      recreational sports. METHOD: Survey of 484 recreational athletes in 11 gyms in
      the area of Frankfurt/Main. RESULTS: 12.9% of the men and 3.6% of the women
      reported to take anabolic drugs. Theyconsumed anabolic steroids (100%; 35% p.o.,
      71% parenterally), stimulants (14%) and growth hormone (5%). Suppliers were
      friends (39%), sports mates (28%), physicians (28%) and coaches (6%). The
      acquisition costs amounted to an average intake over 9 weeks to 175 Euro.
      Information about doping side effects came from literature (67%), physicians
      (38%), sports mates and the so-called Black Book (14% respectively), coaches,
      friends and Internet (5% respectively). 2% of the athletes with abuse of doping
      substances were smokers, 11% had a drink several times a week, 3% also consumed
      other drugs, 35% had consumed other drugs in the past. Abusers of doping
      substances primarily intended to increase muscle size (86%) and strength (61%).
      CONCLUSION: From a sports medical point of view it is concerning that the
      proportion of doping drugs prescribed by physicians has doubled in the decade
      after the publication of the predecessor study in Northern Germany despite
      optimized sports medical and legal education measures.

PMID- 24930321
TI  - [Palliative home care in Westfalia-Lippe--baseline study 12 and 36 months after
      coming into effect of the "agreement to the implementation of ambulant home
      palliative careforterminally ill patients"].
AB  - BACKGROUND: On 2009-04-01 the Association of Statutory Health Insurance
      Physicians Westfalia-Lippe and health insurance organizations made an agreement
      to implement palliative home care for terminally ill patients. Based on this
      agreement, family doctors and palliativecardoctorscooperate,supported by
      coordinators. METHOD: 12 and 36 months after coming into effect of the agreement
      a questionnaire was sent to the regional palliative care networks to collect data
      about supply structure, number of patients and their place of death. RESULTS: In
      the year 2011 85,410 people died in Westfalia-Lippe, 9.0% of them were included
      in palliative care structures. 69.5% of the included patients died at home, 9.9%
      in hospital (in 2010: 68.7% at home, 14.7% in hospital). A correlation between
      the population density or the number of included patients per palliative
      networkcould not be detected. CONCLUSION: Low-threshold access to palliative care
      networks(bothfamilydoctorand patientcancontact the palliative care team at any
      time) improves ambulant palliative care. Non-bureaucratic change from general
      home palliative care (German abbreviation: AAPV) to specialized home palliative
      care (SAPV) has proven successful in Westfalia-Lippe. Well-trained and
      experienced coordinators guarantee multidisciplinary and multiprofessional
      working of palliative care teams. In order to enhance palliative care in
      Westfalia-Lippe, data for quality assurance should be defined, periodically
      collected and evaluated in the future.

PMID- 24930322
TI  - [Innovative wound care--new studies to increase evidence].
AB  - BACKGROUND: Today numerous products for wound care are available. A research
      based evidence on which the clinician can base its selection, is still missing.
      In the guidelines randomized controlled trials (RCTs) have been left out. METHOD:
      In the overview three current RCT with products for the treatment of chronically
      venous ulcers will be presented. RESULTS AND CONCLUSIONS: The pre-mentioned
      studies show, that it is possible to provide a basis for evidence-based treatment
      in wound healing. The effective value ofa wound treatment based on the costs and
      benefits must be defined by the health system. But products, for which data from
      randomized trials exist, should be evaluated in a different way to products, for
      which there are no such data.

PMID- 24930323
TI  - [Pain treatment decisions--relevance of health-related quality of life in family
      medicine].
AB  - BACKGROUND: The reduction of pain is no longer regarded as the predominant
      objective of pain therapy. Pain-related impairments in quality of life or daily
      activities, and anxietyand depression--all of which worsen with progressing pain
      chronification--increasingly gain importance. Impairments in quality of life in
      particular often have a greater impact on patients afflicted by pain than by
      other chronic diseases. METHOD: The present overview explains the importance of
      the parameter health-related quality of life in the treatment of pain patients in
      family medicine; in addition, a variety of tools forthe initial and follow-up
      assessment of pain and pain-related impairments are introduced. RESULTS AND
      CONCLUSION: In addition to a mandatory comprehensive pain diagnostic work-up,
      pain-related restrictions in daily activities and in quality of life should be
      documented in primary care facilities and considered in pain management
      approaches. In a multimodal therapy setting, family practitioners have a key role
      in thediagnosis of pain and in particularalso in the diagnosis of additional
      symptoms and impairments accompanying pain.

PMID- 24930324
TI  - [Influence of tapentadol retard on functional parameters in patients with severe
      chronic pain--is there a benefit in daily life?].
AB  - BACKGROUND: A patient-orientated therapy management for patients with severe
      chronic pain includes effective analgesia, improvement of health related quality
      of life and improvement of functionality. PATIENTS AND METHOD: In this
      prospective, non-interventional trial in 630 patients with severe chronic pain
      mostly due to chronic low back pain or gonarthrosis, treatment with tapentadol
      retard was evaluated with respect to its effects on analgesia, functionality and
      quality of life. Collected data included pain intensity, painDETECT,SF-12, FFbH-R
      and FFbH-OA. RESULTS: Mean pain intensity decreased significantly (NRS-3: -3.2
      points, p < or = 0.001) and in 47.9% of the patients the mean pain intensity was
      reduced by at least 50%. Health-related quality of life and functionality
      improved significantly. Tolerability was good. The known tolerability profile of
      tapentadol retard could be confirmed. CONCLUSION: In this study in real-life
      setting tapentadol was effective in terms of analgesic effect but also in terms
      of improvementof health-related quality of life and functionality, leading to a
      benefit for the patient in daily life.

PMID- 24930325
TI  - [Physician's role in "medical drama" pitfall? Reflection of stereotypical images
      of doctors in context of contemporary doctor's series].
AB  - In contemporary U.S. doctor's series, the characters are usually represented by
      good-looking or typical character actors. The aim of our pilot study was to
      investigate whether the long-term impact of this format on German television
      viewers could have an influence on the choice of doctor in Germany. Two different
      groups of people anticipating TV consumption patterns were questioned: a first
      group of younger adults who knew theTV series was asked to judge their doctor
      choice using a web-based survey tool with respect to three criteria (sympathy,
      expertise and own treatment preference). The second group of adults beyond the
      40th year of life who need not know theTV series were shown photos of the serial
      figures. Study participants should select the "doctor" of which they would most
      likely want to be treated and this based on two predetermined reasons (sympathy
      or expertise). Our results indicate that stereotypical images of doctors found
      high approval only in the first group of people, while the participants in the
      second group decided in majorityfora more realistic representation of average
      appearance.

PMID- 24930326
TI  - [Atrial fibrillation and regular tachycardia in two young patients--are both
      treated with atrial fibrillation ablation?].
AB  - Two young patients with documented episodes of symptomatic paroxysmal atrial
      fibrillation have been referred for pulmonary vein isolation. Both patients had a
      history of concomitant regular tachycardia. in both cases pulmonaryvein isolation
      has not been performed but in each patient a supraventricular tachycardia (right
      focal atrial tachycardia/atrioventricular reentry tachycardia) could be induced
      and ablated instead. Concomitant supraventricular tachycardia acting as a trigger
      arrhythmia is frequent in young patients with atrial fibrillation without
      underlying cardiacdisease. In these patients a concomitant supra-ventricular
      tachycardia should beexcluded by electrophysiological study or ablated before
      pulmonary vein isolation or initiating an antiarrhythmic drug therapy. In most
      cases ablation of supraventricular tachycardia is safe and successful whereas the
      risks of ablative therapy of atrial fibrillation can not be neglected and success
      is moderate.

PMID- 24930327
TI  - [Vacuum shoe system vs.forefoot offloading shoe for the management of metatarsal
      fractures. A prospective, randomized trial].
AB  - BACKGROUND: Metatarsal fractures are managed using different types of forefoot
      offloading orthosis. Theaim of this prospective study was to evaluate the
      clinical and pedographic results of a vacuum shoe system in comparison to a
      forefoot unloading shoe. METHOD: 20 patients (14 women/6 men--age: 36.4 +/- 14.1
      years) were prospectively included in the study. The patients were followed up at
      four different time points. Detailed clinical and radiological examinations were
      carried out, functional scores were measured and a pedographic assessment was
      performed. RESULTS: Between the study groups no differences were seen in
      functional scoring. A complete bony healing was achieved within the 3 months of
      followup in all patients. The heelstrike to heelstrike time was without
      significant differences in the pedographic analysis. Adequate forefoot unloading
      was achieved with both orthosis. The load sharing between fore-, mid- and
      hindfoot showed no significant differences in the pedographic analysis. Patients'
      satisfaction was rated with higher values for the vacuum shoe system, but without
      significance. CONCLUSION: Both shoe systems show an adequate unloading of the
      forefoot. Therefore both orthosis may be used for the treatment of metatarsal
      fractures.

PMID- 24930328
TI  - [Saccharomyces boulardii in the treatment and prevention of antibiotic-associated
      diarrhea].
AB  - BACKGROUND: Antibiotic-associated diarrhea (AAD) is the most frequent side effect
      of antibiotic therapy. Clinical signs and symptoms comprise mild and self
      limiting courses of diarrhea as well as life threatening courses like
      pseudomembranous colitis or toxic megacolon. Therapy is symptomatic,
      antidiarrheal drugs like Saccharomyces boulardii are the therapy of choice.
      METHOD: Available studies on S. boulardii in the prevention of AAD are presented
      as a review. RESULTS: In 14 out of 17 studies including 4,627 patients the
      administration of S. boulardii achieved a protective effect between 43.7% and
      87.3%. A meta-analysis (5 studies, 1,076 patients) showed a significant reduction
      of the risk to develop an AAD from 17.2% to 6.7%,in a furthermeta-analysis (4
      studies on eradication of H. pylori, 1,215 patients) the significant
      reductionwasfrom 12.2% to 5.6%. CONCLUSIONS: There is very good evidence for the
      yeast S. boulardii to be effective in the prevention of AAD especially in
      hospitalized adults. The simultaneous administration of S. boulardii to
      antibiotics resulted in a significant reduction to develop AAD by more than half.

PMID- 24930329
TI  - [Oral osmotic hydromorphone (OROS) in patients with chronic severe pain due to
      osteoarthritis under daily routine conditions].
AB  - OBJECTIVE: Objective of this prospective, non-interventional study was to obtain
      data under a therapy with oral osmotic hydromorphone (OROS) in patients with
      chronic severe pain due to osteoarthritis under daily routineconditions. METHOD:
      Using the Brief Pain Inventory (BPI) patients assessed pain relief as well as the
      impact of pain on activities of daily living. Pain control, treatment
      satisfaction (by patient and investigator), physical therapy capability and the
      WOMAC-Index (Western Ontario and McMaster Universities Osteoarthritis) were
      additionally evaluated. Adverse events were continuously monitored throughout the
      study. RESULTS: 206 patients with chronic severe pain due to osteoarthritis and
      an initial pain intensity of 6 (NRS 0-10) received oral OROS-hydromorphone for
      three months. Under this treatment pain relief as well as the impact of pain on
      activities of daily living improved significantly. At the last examination, the
      patients reported a mean pain reduction of 2.5 (rest)/3.0 (movement) by day and
      of 2.6 (rest)/3.1 (movement) bynight (p < 0.0001). The very good pain control was
      accompanied by a high treatment satisfaction and an improved sleep quality.
      Physical therapy capability improved in 77.9% of the patients, the WOMAC index as
      indicator of pain and function in osteoarthritis decreased significantly from
      13.3 (baseline) to 7.5 (V6). The most frequently reported adverse events were
      obstipation, nausea, dizziness and fatigue. 17.5% of the patients cut the study
      short because of adverse events. CONCLUSION: The treatment of patients with
      chronic pain due to osteoarthritis with oral osmotic hydromorphone resulted in a
      significant reduction of all documented pain related assessments.

PMID- 24930330
TI  - [Patient with bladder catheter. Why is the urine turning purple? Purple urine bag
      syndrome].

PMID- 24930331
TI  - [Satellite practice can also be approved for office wait time].

PMID- 24930332
TI  - [Proper fee claims for palliative medicine care].

PMID- 24930333
TI  - [The new laboratory compendium by the KBV carries a significant regress
      potential].

PMID- 24930334
TI  - [Bomb simulation in nail care].

PMID- 24930335
TI  - [Cooperation among medical specialties. Medicine is the responsibility of
      physicians].

PMID- 24930336
TI  - ["Turbo-Check-up" for 1,000 euros. Is this really of any value?].

PMID- 24930337
TI  - [What helps control shoulder pain. Hot wraps - radiation - operation].

PMID- 24930338
TI  - [Treatment refractory hypertension. When should an endocrine etiology be
      considered?].

PMID- 24930339
TI  - [Vital to the grave].

PMID- 24930340
TI  - [Do acid blockers induced food allergies in children?].

PMID- 24930341
TI  - [Gold rush in the knee].

PMID- 24930342
TI  - [A stent in renal artery stenosis is not necessary].

PMID- 24930343
TI  - [Livelong medical education].

PMID- 24930344
TI  - [Vaccination recommendations].

PMID- 24930345
TI  - [Update Rheumatoid Arthritis 2014].

PMID- 24930346
TI  - [Hyper- and hypothyroidism].

PMID- 24930347
TI  - [Osteoporosis in men].

PMID- 24930348
TI  - [Treatment strategies atrial fibrillation].

PMID- 24930349
TI  - [Early diagnosis of pulmonary diseases].

PMID- 24930350
TI  - [Patient with fever].

PMID- 24930351
TI  - [Multiple sclerosis: new treatment options].

PMID- 24930353
TI  - [Placebo analgesia].

PMID- 24930352
TI  - [National practice guideline therapy of type 2 diabetes].

PMID- 24930354
TI  - Endoscopic treatment of a broken pancreatic stent.

PMID- 24930355
TI  - Evaluation of anti-inflammatory activity of hydroethanolic extract of Dilodendron
      bipinnatum Radlk.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dilodendron bipinnatum Radlk. (Sapindaceae),
      popularly known as "mulher-pobre", is a native tree of the Pantanal of Mato
      Grosso, Brazil. The stem bark of Dilodendron bipinnatum is used by the
      population, in the forms of decoction and maceration in the treatment of
      inflammatory conditions. There is no information in the literature demonstrating
      the anti-inflammatory activity of Dilodendron bipinnatum and its respective
      mechanism of action. This study aimed to evaluate the anti-inflammatory activity
      and mechanism of action of the hydroethanolic extract of the stem bark of
      Dilodendron bipinnatum (HEDb) using in vivo and in vitro experimental models.
      MATERIALS AND METHODS: The stem bark of Dilodendron bipinnatum was macerated in
      70% hydroethanolic solution (1:3, w/v) for 7 days, filtered, concentrated on a
      rotary evaporator and the residual solvent removed in oven at 40 degrees C, thus
      obtaining HEDb. Cytotoxicity of HEDb in RAW 264.7 was assessed by the Alamar blue
      assay. in vivo anti-inflammatory activity of HEDb was evaluated with carrageenan
      and dextran-induced paw edemas and lipopolysaccharide (LPS)-induced peritonitis
      in mice. Effects of HEDb on the inflammatory cytokines (TNF-alpha, IL-1beta and
      IL-10) concentrations in the peritoneal fluid were evaluated using commercial
      ELISA kits. The in vitro anti-inflammatory activity was evaluated using RAW 264.7
      cells stimulated with LPS and/or INF-gamma, while a Griess method was employed to
      determine nitric oxide (NO) concentrations in the peritoneal lavage and in the
      supernatants of RAW 264.7 cells. Preliminary phytochemical analysis was carried
      out using classical methods and secondary metabolites detected on HEDb were
      analyzed and confirmed by high performance liquid chromatography (HPLC). RESULTS:
      HEDb showed very low cytotoxicity with IC50>200+/-0.38 MUg/mL. HEDb effectively
      inhibited paw edema by carrageenan in the 2nd hour at 20 mg/kg (36%, p<0.001),
      and by dextran in the 1st hour at 100 mg/kg (46%, p<0.01), after induction with
      the phlogistic agents. Furthermore, HEDb reduced total leukocytes and neutrophils
      migration at all doses tested producing maximum effect at 20 mg/kg (45% and 64%,
      p<0.001 respectively). HEDb also attenuated increases in the concentrations of
      the pro-inflammatory cytokines (IL-1beta and TNF-alpha) and increased the level
      of the anti-inflammatory cytokine IL-10 in the peritonitis model. However, it had
      no effect on NO production in activated RAW 264.7 cells. Preliminary
      phytochemical analysis revealed the presence of phenolic compounds, chalcones,
      flavones, flavonones, flavonoids, saponins and coumarins. HPLC analyses
      identified some tannins, with epigallocatechin gallate being the major compound.
      CONCLUSIONS: Our findings provide evidence for the popular use of the stem bark
      of Dilodendrum bipinnatum in inflammation. Its anti-inflammatory action was due,
      at least in part, to the inhibition of cell migration, of the inflammatory
      mediators and Th1 cytokines and an increase in Th2 cytokines, without affecting
      NO pathway. It can be suggested that tannins account at least in part for the
      anti-inflammatory activity of HEDb.

PMID- 24930356
TI  - The effects of wine-processing on ascending and descending: The distribution of
      flavonoids in rat tissues after oral administration of crude and wine-processed
      Radix scutellariae.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ascending and descending theory is a core
      principle of traditional Chinese medicine (TCM) theories. It plays an essential
      role in TCM clinical applications. Some TCM medicine has specific properties,
      which could alter the inclination and direction of their actions. The properties
      of the ascending and floating process of one herbal medicine are affected by
      means of herb processing. Wine-processing, which is sauteing with rice wine, is
      one of the most popular technologies of herb processing. Wine-processing
      increases the inclination and direction of its actions, thereby producing or
      strengthening their efficacy in cleaning the upper-energizer heat. Radix
      scutellariae, the dried roots of Scutellaria baicalensis Georgi, is a well-known
      TCM used for the treatment of inflammation, pyrexia, jaundice, etc. Recently,
      wine-processed Radix scutellariae was normally applied in clinical studies for
      the treatment of upper-energizer syndrome. In order to investigate the effects of
      wine-processing on ascending and descending of Radix scutellariae, the
      comparative study of distribution of flavonoids in rat tissues of triple
      energizers (SanJiao-upper, middle, lower jiao) after oral administration of crude
      and wine-processed Radix scutellariae aqueous extracts was carried out. MATERIALS
      AND METHODS: The rats were randomly assigned to two groups and orally
      administered with crude and wine-processed Radix scutellariae aqueous extracts,
      respectively. At different pre-determined time points after administration, the
      concentrations of compounds in rat tissue homogenate were determined, and the
      main tissue pharmacokinetic parameters were investigated. Tissue pharmacokinetic
      parameters including AUC0-t, t1/2, Tmax and Cmax were calculated using DAS 2.0.
      An unpaired Student t-test was used to compare the differences in tissue
      pharmacokinetic parameters between the two groups. All the results were expressed
      as arithmetic mean+/-S.D. RESULTS: The parameters of Cmax and AUC0-t of some
      flavonoids in wine-processed Radix scutellariae were remarkably increased
      (p<0.05, p<0.01, p<0.001) in the rat upper-energizer tissues (lung and heart)
      compared with those of the crude group. However, in the rat middle- and lower
      energizer tissues (spleen, liver and kidney), the Cmax and AUC0-t of some
      flavonoids were significantly decreased (p<0.05, p<0.01) compared with the crude
      group. The main explanation for these differences seems to the effects of wine
      processing on ascending and descending theory. CONCLUSIONS: All of these
      differences in the distribution of triple energizers after oral administration of
      crude and wine-processed Radix scutellariae aqueous extracts may lead to the
      increase of efficacy on the upper-energizer tissues and were in compliance with
      the ascending and descending theory. Therefore, wine-processing was recommended
      when Radix scutellariae was used for cleaning the upper-energizer heat and
      humidity. The obtained knowledge can be used to evaluate the impact of these
      differences on the efficacy of both the drugs in clinical applications and might
      be helpful in explaining the effects of wine-processing on ascending and
      descending theory.

PMID- 24930357
TI  - Calycosin-7-O-beta-D-glucoside regulates nitric oxide /caveolin-1/matrix
      metalloproteinases pathway and protects blood-brain barrier integrity in
      experimental cerebral ischemia-reperfusion injury.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Astragali Radix (AR) has been used for thousands
      years to treat ischemic stroke. Calycosin and its glycoside form calycosin-7-O
      beta-D-glucoside (CG) are two representative isoflavones in Astragali Radix.
      However, its neurological effects and related molecular mechanisms are largely
      unknown. The present study aims to evaluate the neuroprotective effects of CG on
      blood-brain barrier (BBB) integrity of ischemic brain tissue and explore the
      relevant signaling mechanisms. MATERIAL AND METHOD: Male adult Sprague-Daweley
      rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 24 h
      or 14 days of reperfusion. CG (26.8 mg/kg) was intraperitoneally administered
      into the rats at 15 min before onset of ischemia. The neuroprotective effects of
      CG were evaluated by measuring infarct volume, histological damage and BBB
      permeability. Furthermore, the effects of CG on scavenging nitric oxide (NO), and
      modulating matrix metalloproteinases (MMPs) and caveolin-1 (cav-1) were
      investigated with in vitro cultured brain microvascular endothelial cells treated
      with NO donor or oxygen-glucose deprivation (OGD) and/or in vivo rat model of
      MCAO cerebral ischemia-reperfusion injury. RESULTS: CG treatment significantly
      reduced infarct volume, histological damage and BBB permeability in the in vivo
      MCAO ischemia-reperfusion rat model. CG treatment remarkably inhibited the
      expression and activities of MMPs, and secured the expression of cav-1 and tight
      junction proteins in the microvessels isolated from ischemic rat cortex.
      Furthermore, CG was revealed to scavenge NO, inhibit the activities of MMP-2 and
      MMP-9, and attenuate cell death in the in vitro cultured brain microvascular
      endothelial cells under OGD condition. CONCLUSION: CG could protect BBB integrity
      in experimental cerebral ischemia-reperfusion injury via regulating NO/cav-1/MMPs
      pathway.

PMID- 24930358
TI  - Effects of Sceletium tortuosum in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Broad historical and current uses in addition to
      diverse activity on CNS targets may make Sceletium tortuosum a useful therapeutic
      in a variety of clinical settings. This study sought to more broadly characterize
      activity of Sceletium tortuosum and mesembrine in a number of common, rodent
      based assays that model nociception, depression, anxiety, ataxia, and abuse
      liability. MATERIALS AND METHODS: Male Sprague-Dawley were administered Sceletium
      tortuosum extract products and behavioral responses were evaluated in the
      conditioned place preference (CPP), hot plate, forced swim, elevated plus, and
      rotarod tests. RESULTS AND CONCLUSIONS: Sceletium tortuosum does not cause
      preference or aversion in CPP. Mesembrine appears to have analgesic properties
      without abuse liabilities or ataxia. The Sceletium tortuosum fraction has
      antidepressant properties but does produce ataxia. The ataxia may limit its
      usefulness as an antidepressant unless the antidepressant activity is associated
      with one constituent and the ataxia is associated with a separate constituent.

PMID- 24930359
TI  - Short-term, low-dose varenicline administration enhances information processing
      speed in methamphetamine-dependent users.
AB  - Long-term, high-dose methamphetamine (METH) use is associated with decrements in
      neurocognition and, given the association between impaired neurocognition and
      poorer treatment outcomes in individuals dependent on alcohol and drugs, it is
      considered to be a neglected area of critical concern. The objective of this
      study was to determine whether varenicline, a partial agonist at alpha4beta2- and
      a full agonist at alpha7-nicotinic acetylcholine receptors, enhances
      attention/information processing speed, episodic memory, and working memory in
      non-treatment seeking METH-dependent participants. Twenty-six participants were
      randomly assigned to receive oral placebo or oral varenicline (titrated up to 1
      mg) over 5 days during three separate inpatient phases, and 17 completed each
      inpatient phase. Participants were predominately male (71%) and Caucasian (71%).
      Varenicline significantly improved reaction time on the n-back for visual stimuli
      (F(1,47)=5.369, p=0.025, eta2=0.103), and a trend was observed for improvement in
      reaction time for auditory stimuli (F(1,47)=3.141, p=0.083, eta2=0.063). For
      those study participants whose reaction time was in the lower half of the
      distribution at baseline, the effect was even more pronounced for auditory
      (F(1,22)=5.287, p=0.031, eta2=0.194) and visual (F(1,22)=11.981, p=0.002,
      eta2=0.353) stimuli relative to placebo. In contrast, varenicline did not
      modulate mean or maximum span of working memory or performance on tests of
      episodic memory or attention (p's>0.05). Given the potential importance of this
      finding, it should be replicated in a larger sample over a longer treatment
      period with a higher dose of varenicline (2 mg). TRIAL REGISTRATION:
      clinicalTrials.gov Identifier NCT01571167.

PMID- 24930360
TI  - Benzodiazepine ligands rapidly influence GABAA receptor diffusion and clustering
      at hippocampal inhibitory synapses.
AB  - Benzodiazepines (BZDs) are widely used in the treatment of a variety of
      neurological and psychiatric conditions including anxiety, insomnia and epilepsy.
      BZDs are thought to act predominantly by affecting the gating of GABAA receptor
      channels, resulting in enhanced GABA-mediated currents in neurons. However,
      mutations mimicking the effect of BZDs on GABAAR channel gating have been shown
      to also impact the membrane dynamics and synaptic anchoring of the receptors.
      Here, using single molecule tracking combined with electrophysiological
      recordings, we show that BZD ligands rapidly influence the dynamic behavior of
      GABAARs in hippocampal neurons. Application of the inverse BZD agonist DMCM
      rapidly increased the diffusion and reduced the clustering of GABAARs at
      synapses, resulting in reduced postsynaptic currents. Conversely, the BZD full
      agonist diazepam had little effect at rest but reduced lateral diffusion and
      increased synaptic stabilization and clustering of GABAARs upon sustained
      neuronal activity, resulting in enhanced potency of inhibitory synapses. These
      effects occurred in the absence of detectable changes in gephyrin clusters,
      suggesting they did not reflect a rapid dispersion of the synaptic scaffold.
      Thus, alterations of the diffusion and synaptic anchoring of GABAARs represent a
      novel, unsuspected mechanism through which BZDs rapidly modulate GABA signaling
      in central neurons.

PMID- 24930362
TI  - August 2014: critical care in transition.

PMID- 24930361
TI  - Lenalidomide and dexamethasone for systemic AL amyloidosis following prior
      treatment with thalidomide or bortezomib regimens.
AB  - The outcomes and responses to treatment remain poorly studied among patients with
      systemic AL amyloidosis who require further treatment following prior novel agent
      based therapy. We report here treatment with lenalidomide-dexamethasone in 84 AL
      amyloidosis patients with relapsed/refractory clonal disease following prior
      treatment with thalidomide (76%) and/or bortezomib (68%). On an intention-to
      treat (ITT) basis, the overall haematological response rate was 61%, including
      20% complete responses. The median overall survival (OS) has not been reached; 2
      year OS and progression-free survival (PFS) was 84% and 73%, respectively.
      Achieving a free light chain (FLC) response was an independent good prognostic
      factor for OS in multivariate analysis. There was no impact of prior thalidomide
      or bortezomib therapy on response rate, OS or PFS. 16% achieved an organ response
      at 6 months, with a marked improvement in organ responses in patients on long
      term therapy (median duration 11 months) and 55% achieving renal responses by 18
      months. Lenalidomide/dexamethasone therapy achieves good haematological responses
      in patients with AL amyloidosis with relapsed/refractory clonal disease. The rate
      of renal responses among patients who received prolonged treatment was
      unexpectedly high, raising the possibility that immunomodulatory effects of
      lenalidomide therapy might enhance the otherwise slow natural regression of
      amyloid deposits. 

PMID- 24930363
TI  - Correlation of corrected flow time in the carotid artery with changes in
      intravascular volume status.
AB  - PURPOSE: Assessment of volume status remains a challenge in critical care. Our
      purpose was to determine if Doppler waveform analysis of carotid artery blood
      flow correlates with changes in volume status. MATERIALS AND METHODS: Dehydrated
      patients receiving an intravenous fluid bolus were enrolled with exclusions
      including age less than 18 years, pregnancy, vasopressor administration, or
      atrial fibrillation. Ultrasound examination with Doppler analysis of the carotid
      artery was performed with measurements taken to calculate corrected flow time
      (FTc). Corrected flow time, mean arterial pressure, and pulse rate before and
      after fluid administration were compared using Wilcoxon matched-pairs signed rank
      test. RESULTS: Fifty-six patients were enrolled with mean fluid administration of
      1110 mL. Corrected flow time increased with fluid resuscitation from prefluid
      mean of 299 milliseconds (95% confidence interval [CI], 282-317 milliseconds) to
      a postfluid mean of 340 milliseconds (95% CI, 323-358 milliseconds) (P<.0001).
      Mean percentage change in FTc was 14.9% (95% CI, 8.4-21.3). There were no
      significant changes in mean arterial pressure or heart rate from pre- to post
      fluid administration. CONCLUSION: Intravenous fluid administration in dehydrated
      patients resulted in significant changes in FTc in the carotid artery despite no
      change in vital signs. Corrected flow time measured from carotid arterial blood
      flow may be a useful means of assessing volume status in volume-depleted
      patients.

PMID- 24930364
TI  - From data patterns to biological mechanism in critical illness: the role of
      engineering.

PMID- 24930365
TI  - Supporting small steps toward big innovations: the importance of rigorous pilot
      studies in critical care.

PMID- 24930366
TI  - Death by neurologic criteria 1968-2014: changing interpretations. Forward.

PMID- 24930367
TI  - History of brain death as death: 1968 to the present.
AB  - The concept of brain death was formulated in 1968 in the landmark report A
      Definition of Irreversible Coma. While brain death has been widely accepted as a
      determination of death throughout the world, many of the controversies that
      surround it have not been settled. Some may be rooted in a misconstruction about
      the history of brain death. The concept evolved as a result of the convergence of
      several parallel developments in the second half of the 20th century including
      advances in resuscitation and critical care, research into the underlying
      physiology of consciousness, and growing concerns about technology, medical
      futility, and the ethics of end of life care. Organ transplantation also
      developed in parallel, and though it clearly benefited from a new definition of
      death, it was not a principal driving force in its creation. Since 1968, the
      concept of brain death has been extensively analyzed, debated, and reworked.
      Still there remains much misunderstanding and confusion, especially in the
      general public. In this comprehensive review, I will trace the evolution of the
      definition of brain death as death from 1968 to the present, providing
      background, history and context. 

PMID- 24930368
TI  - Spectrum of catastrophic brain injury: coma and related disorders of
      consciousness.

PMID- 24930369
TI  - Pathophysiology of brain death: what does the brain do and what is lost in brain
      death?

PMID- 24930370
TI  - Biophilosophical basis for identifying the death of a person.
AB  - The capacity for consciousness and self-awareness is uniquely synonymous with
      human life and personhood, and its absence is necessary and sufficient to
      identify that death has occurred. The presence of these functions is uniquely
      synonymous with human life. Ongoing organ function, response to infection,
      growth, wound healing, or the ability to sustain an unborn fetus do not alone
      constitute the unique experience of life and personhood. Death occurs after the
      loss of the ability to use oxygen by the brain, which occurs because of either
      raised intracranial pressure preventing any cerebral blood flow or, more
      commonly, the absence of systemic blood flow following abrupt or hypoxic
      circulatory cessation. The abrupt cessation of circulation leads to loss of
      consciousness and brain electrical activity; and when it becomes truly permanent
      and then irreversible, this becomes an operational definition of death. One must
      infer and decide that sufficient ischemic hypoxic injury has rendered the
      potential for reinstating any consciousness and brain stem function irreversibly
      lost. Progressive hypoxia that is seen in many patients after withdrawal of
      advanced physiologic support leads to apnea and then circulatory arrest. The
      outward sign of apnea that is then followed by circulatory arrest is the basis
      for inferring that irreversible loss of capacity for consciousness and self
      awareness has occurred and that death can be identified has having occurred. The
      capacity for consciousness and self-awareness is the only irreplaceable emergent
      phenomenon-arising from physiologic function of the brain-that is necessary and
      sufficient to define the life of a person.

PMID- 24930371
TI  - Normalization patterns of the surface electromyographic signal in the phonation
      evaluation.
AB  - PURPOSE: The aim of the study was to compare the different parameters, regarding
      the peak and mean, at different phonatory tasks for standardization of
      electromyography signal of electrical activity (EA) of the laryngeal extrinsic
      muscles on voice evaluation. METHODS: The electrical potentials of the suprahyoid
      (SH) and infrahyoid (IH) muscles of 35 voluntary nondysphonic subjects were
      evaluated using three evaluations of rest, two maneuvers to determine maximum
      voluntary sustained activity (MVSA), and usual and strong intensity of vowel /E/
      and 20-30 count emissions. The EA signal was converted using root mean square in
      microvolts and normalized by mean and peak of each task. The selected
      normalization task was that with minor coefficient of variation for all muscles.
      RESULTS: The tasks that provided minor coefficient of variation of EA in both
      muscle groups were the peak of vowel /E/ (mean potentials equal to 43.31 +/- 2.97
      for right IH, 36.27 +/- 2.76 for left IH, and 42.11 +/- 2.57 for SH) and the 20
      30 count emissions (mean potentials equal to 31.30 +/- 308 for right IH, 30.56 +/
      2.76 for left IH, and 30.43 +/- 4.22 for SH), both in usual intensity and MVSA,
      as second option. CONCLUSIONS: The peak of vowel /E/ and 20-30 count emissions is
      usual intensity, and the MVSA as second option should be considered for signal
      normalization in SH and IH muscles, and may provide conditions for using the
      surface electromyography in voice clinic.

PMID- 24930372
TI  - Immediate effects of humming on computed electroglottographic parameters in
      patients with muscle tension dysphonia.
AB  - OBJECTIVES: To investigate the immediate effects of humming and subsequent um-hum
      phonation on the computed parameters of electroglottographic (EGG) signals in
      muscle tension dysphonia (MTD) patients and nondysphonic speakers. METHODS: We
      included 21 MTD participants exhibiting both vocal roughness and supraglottic
      compression, who were able to produce successful humming and um-hum phonation.
      Twenty nondysphonic participants were selected as controls. Each participant was
      instructed to perform three phonatory tasks: natural phonation, humming phonation
      without pitch changes, and subsequent um-hum phonation, that is, humming with a
      pitch glide up as if agreeing with someone. Acoustic and EGG signals were
      recorded while the participants performed these tasks. Computed parameters
      reflecting the irregularities in vocal fold vibrations and the degree of glottal
      contact were calculated and compared between the tasks. RESULTS: The MTD group
      showed decreases in both perceptual vocal roughness and acoustic perturbation
      parameters while performing the tasks. The perturbation parameters of EGG signals
      and the standard deviation of the contact quotient (CQ) also exhibited
      significant decreases associated with either of humming or um-hum phonation in
      both groups. In addition, the CQ exhibited significant increases following
      humming alone in the MTD group and the combination of humming and um-hum
      phonation in both groups. CONCLUSIONS: These results suggest that the combination
      of humming without pitch changes and subsequent um-hum phonation have the
      immediate effect in adjusting the regularity of vocal fold vibration and
      augmenting the degree of glottal contact in MTD patients as well as nondysphonic
      speakers, whereas humming alone increases the degree of glottal contact in MTD
      patients.

PMID- 24930374
TI  - Laryngeal actinomycosis in an immunocompromised patient.
AB  - Actinomycosis of the larynx represents an unusual presentation for a common
      bacterium comprising the oral and oropharyngeal florae. There are few cases
      reported in the literature of laryngeal actinomycosis occurring primarily in the
      immunocompromised population. Here, we present a case in a 74-year-old man that
      occurred in the setting of neutropenia as a result of chemotherapy. Once the
      diagnosis was made with biopsy of the larynx, the infection was resolved after a
      prolonged course of penicillin-based therapy. 

PMID- 24930373
TI  - Psychosocial distress in patients presenting with voice concerns.
AB  - OBJECTIVES: To assess the prevalence of psychosocial distress (depression,
      anxiety, somatization, and perceived stress) in a consecutive sample of patients
      presenting with voice concerns and to qualitatively analyze patient comments on
      challenges associated with voice problems. STUDY DESIGN: Cross-sectional study.
      METHODS: New patients presenting to a multidisciplinary voice clinic with voice
      concerns were invited to participate. Respondents (n = 197) completed the Brief
      Symptom Inventory 18-item scale, the 4-item Perceived Stress Scale, and the Voice
      Handicap Index 10-item scale. Qualitative analysis was performed of responses to
      an open-ended question about challenges associated with a voice problem. RESULTS:
      Approximately one-third (32%) of the patients met the strict case criteria for
      depression, anxiety, and/or somatic concerns based on the Brief Symptom Inventory
      18-item scale. Most patients had no prior diagnosis of depression or anxiety, and
      the degree of distress was not predicted by the type of voice-related diagnosis.
      Perceived stress was higher among female patients (P = 0.02). As expected, scores
      on the Voice Handicap Index 10-item scale were indicative of concurrent voice
      related handicap (mean, 19.5; standard deviation, 9.4). In qualitative analysis
      of responses regarding challenges associated with a voice problem, 19 themes were
      identified (eg, threat to occupational functioning). CONCLUSIONS: These findings
      identify a high prevalence of multiple types of distress among patients with
      voice disorders, presenting an opportunity to provide more comprehensive care to
      this patient population.

PMID- 24930375
TI  - Recycling bacteria for the synthesis of LiMPO4 (M = Fe, Mn) nanostructures for
      high-power lithium batteries.
AB  - In this work, a novel waste-to-resource strategy to convert waste bacteria into a
      useful class of cathode materials, lithium metal phosphate (LiMPO4; M = Fe, Mn),
      is presented. Escherichia coli (E. coli) bacteria used for removing phosphorus
      contamination from wastewater are harvested and used as precursors for the
      synthesis of LiMPO4. After annealing, LiFePO4 and LiMnPO4 nanoparticles with
      dimensions around 20 nm are obtained. These particles are found to be enveloped
      in a carbon layer with a thickness around 3-5 nm, generated through the
      decomposition of the organic matter from the bacterial cell cytoplasm. The
      battery performance for the LiFePO4 is evaluated. A high discharge capacity of
      140 mAh g(-1) at 0.1 C with a flat plateau located at around 3.5 V is obtained.
      In addition, the synthesized particles display excellent stability and rate
      capabilities. Even under a high C rate of 10 C, a stable discharge capacity of
      75.4 mAh g(-1) can still be achieved.

PMID- 24930377
TI  - Preventing rural workforce by design.

PMID- 24930376
TI  - PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity: a functional
      replication study.
AB  - Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or
      PTK2) is an important component of the human interactome and thus is a potential
      longevity-related protein. Here we studied the association between two PTK2 gene
      single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional
      longevity (EL). In addition to gaining insight into their functionality by
      determining luciferase gene reporter activity, we studied the genotype/allele
      frequency of these two SNPs among three different cohorts: (1) Spanish
      centenarians (n=175, 100-111 years, 144 women) and healthy controls (n=355, 20-50
      years, 284 women); (2) Italian centenarians (n=79, 100-104 years, 40 women) and
      controls (n=316, 29-50 years, 156 women); and (3) Japanese centenarians (n=742,
      100-116 years, 623 women) and healthy controls (n=499, 23-59 years, 356 women).
      Both SNPs had functional significance, with the A allele up-regulating luciferase
      activity compared to the other allele (rs7460 T allele and rs7843014 C allele,
      respectively). The A allele of both SNPs was negatively associated with EL in the
      Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence
      intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001).
      The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI
      4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated
      with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found
      for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460
      TT and rs7843014 CC, are possibly associated with lower gene expression and might
      favor the likelihood of reaching EL in the Spanish population. Further research
      is needed to unveil the mechanisms by which FAK expression could perhaps
      influence the rate of aging.

PMID- 24930378
TI  - The effects of isoflavones on androgens and glucocorticoids during puberty on
      male Wistar rats.
AB  - Isoflavones are the most common phytoestrogens found in human diets. However, it
      is still not clear whether isoflavones have effects on the reproductive and the
      endocrine systems under normal dietary intake and overdose. The aim of this study
      was to determine how the most important isoflavones, genistein and daidzein,
      affect androgen and glucorticoid levels on male prepuberal rats. A hundred and
      seventy-five 30-day-old male Wistar rats were dosed orally by stomach tube every
      day for 35 days, with saline solution, low and high doses of genistein, daidzein
      and a mixture of both. Serum samples were analysed by an enzyme immunoassay for
      hormone determinations. In control group, there was a peak of testosterone (T)
      and dihydrotestosterone levels associated to the onset of puberty, at the third
      week. However, in low-dose groups, the same peak was found at the fourth week (p
      < 0.05), indicating a delay in the onset of puberty in these groups. Moreover,
      high doses groups serum androgen levels were significantly lower (p < 0.05) than
      the control group from the first week until fifth week. This fact was supported
      by a epididymal histological analysis that indicate in low doses there were
      several content of spermatozoa at fourth week and in high doses there were few
      content of spermatozoa. Besides, corticosterone levels followed the same pattern
      of androgens in all groups. We can conclude that oral administration of
      isoflavones in male rats decreased the secretion of androgens and glucocorticoids
      causing a delay in the onset of puberty and may cause physiological and
      developmental problems.

PMID- 24930383
TI  - Elevation of HDL-C in response to statin treatment is involved in the regression
      of carotid atherosclerosis.
AB  - AIM: Atherosclerosis is strongly associated with an increased mortality in
      subjects with diabetes. The carotid intima-media thickness (IMT) is commonly
      measured as a surrogate marker for cardiovascular risk. Statins are well
      established protective agents against atherosclerosis and reportedly suppress IMT
      progression in subjects with diabetes. To clarify the effects of statins on
      subclinical atherosclerosis, we herein investigated changes in the carotid IMT
      and lipid profiles in a multi-center, prospective, randomized trial. METHODS:
      Hypercholesterolemic subjects with type 2 diabetes were randomly assigned to open
      label treatment with either pravastatin or pitavastatin. The primary endpoint of
      this study was the IMT change after 36 months of statin treatment. RESULTS: A
      total of 97 subjects (51 pitavastatin; 46 pravastatin) completed this 36-month
      study. The LDL-C decreased significantly from 163.4 +/- 27.9 mg/dl at baseline to
      100.4 +/- 19.6 mg/dl at 36 months in the pitavastatin group and from 159.7 +/-
      25.6 mg/dl to 118.5 +/- 22.1 mg/dl in the pravastatin group. The mean IMT showed
      moderate regression in both the pitavastatin (-0.070 +/- 0.215 mm, P<0.05) and
      the pravastatin (-0.067 +/- 0.260 mm) group. However, there was no significant
      difference in the IMT change between the two groups. When the two groups were
      combined, the 36-month change in the mean IMT was significantly associated with
      HDL-C change (r=-0.24, P= 0.03). Multiple linear regression analysis revealed the
      change in HDL-C to be an independent variable showing a positive correlation with
      the carotid IMT reduction. CONCLUSION: The administration of statins for 3 years
      to subjects with type 2 diabetes resulted in a significant regression of the
      carotid IMT. An elevation of the plasma HDL-C with statin treatment was closely
      related to a regression of atherosclerosis.

PMID- 24930384
TI  - A replication study and a meta-analysis of the association between the CDKN2A
      rs1333049 polymorphism and coronary heart disease.
AB  - AIM: The aim of this study was to assess whether rs1333049 was associated with
      coronary heart disease (CHD) in Han Chinese. METHODS: This case-control study was
      involved with 599 CHD patients and 591 non-CHD controls. Meanwhile, a
      comprehensive meta-analysis was also conducted to establish the contribution of
      rs1333049 to CHD. RESULTS: Our results showed that rs1333049 increased the risk
      of CHD by 38% (OR=1.38, 95% CI=1.18-1.62). A breakdown analysis by gender further
      indicated that rs1333049 increased the risk of CHD in men by 29% (OR=1.29, 95%
      CI=1.05-1.58) and in women by 64% (OR=1.64, 95% CI=1.25-2.16). A follow-up
      subgroup analysis by age showed there was a significant association between
      rs1333049 and CHD in women younger than 65 (<=55 years: p=0.001, 55-65 years:
      p=0.008) and in men aged between 55 and 65 years (p=0.005). Our meta-analysis was
      involved with 21 studies (25 stages) among 20969 cases and 34114 controls. Our
      results showed that rs1333049 led to a significantly increased risk of CHD
      (OR=1.30, 95% CI=1.21-1.39). Further subgroup analyses by ethnicity showed
      rs1333049 increased the CHD risk by 30% in Europeans (OR=1.30, 95% CI=1.16-1.47)
      and 27% in Asians (OR=1.27, 95% CI=1.22-1.33). CONCLUSIONS: Our case-control
      study and meta-analysis suggest that rs1333049 is a useful risk marker of CHD.

PMID- 24930385
TI  - Expression and activity levels of matrix metalloproteinase-7 and in situ
      localization of caseinolytic activity in colorectal cancer.
AB  - OBJECTIVES: Matrix metalloproteinase-7 is capable of degrading several ECM and
      non-ECM molecules and contributes to colorectal cancer progression and
      metastasis. Here, we examined the significance of MMP-7 in colorectal tumors by
      detecting active and latent MMP-7 levels and localization of its caseinolytic
      activity. DESIGN AND METHODS: We investigated expression levels, localization,
      and proteolytic activity of MMP-7 and local caseinolytic activity in colorectal
      tumor and paired normal tissues by using real time PCR, casein zymography,
      immunohistochemistry and in situ casein zymography, respectively. In addition the
      results were compared with clinicopathological variables. RESULTS: Real time PCR
      and immunohistochemistry showed that MMP-7 expressions were higher in colorectal
      tumor tissues than in normal tissues. Also, mRNA expressions of MMP-7 were
      positively correlated with tumor and pathological stages and negatively
      correlated with age. Furthermore, MMP-7 mRNA expression had a sensitivity of
      81.3% and a specificity of 81.2% at a cut-off value of 0.0006, making it a
      potential marker for diagnosis of colorectal cancer. According to casein
      zymography, pro- and active MMP-7 levels were also elevated in tumor tissues. In
      addition, we assessed local caseinolytic activity using in situ casein
      zymography. Increased immunoreactivity of MMP-7 and local caseinolytic activity
      were found in neoplastic cells but not in stromal cells. CONCLUSION: We
      emphasized the significant role of MMP-7 in diagnosis and progression and/or
      development of colorectal cancer.

PMID- 24930386
TI  - Text messaging interventions for adolescent and young adult substance use: a meta
      analysis.
AB  - Tobacco and alcohol use continues to be associated with negative health outcomes
      among adolescents and young adults. New technologies such as text messaging can
      increase access to substance use interventions and have now been established as
      an evidence-based, recommended approach towards substance use prevention. This
      review presents results from a meta-analysis examining the effectiveness of text
      message interventions for tobacco and alcohol cessation within adolescent and
      young adult populations. Results from 14 studies with effect sizes are ranging
      from -0.25 to 0.54. Combining the effect sizes across studies yielded a summary
      effect size of 0.25, indicating that in general, text interventions have a
      positive effect on reducing substance use behaviors. Results are discussed in the
      context of prevention opportunities and recommendations for future text messaging
      intervention research. 

PMID- 24930387
TI  - In-situ electrochemically deposited polypyrrole nanoparticles incorporated
      reduced graphene oxide as an efficient counter electrode for platinum-free dye
      sensitized solar cells.
AB  - This paper reports a rapid and in-situ electrochemical polymerization method for
      the fabrication of polypyrrole nanoparticles incorporated reduced graphene oxide
      (rGO@PPy) nanocomposites on a ITO conducting glass and its application as a
      counter electrode for platinum-free dye-sensitized solar cell (DSSC). The
      scanning electron microscopic images show the uniform distribution of PPy
      nanoparticles with diameter ranges between 20 and 30 nm on the rGO sheets. The
      electrochemical studies reveal that the rGO@PPy has smaller charge transfer
      resistance and similar electrocatalytic activity as that of the standard Pt
      counter electrode for the I3(-)/I(-) redox reaction. The overall solar to
      electrical energy conversion efficiency of the DSSC with the rGO@PPy counter
      electrode is 2.21%, which is merely equal to the efficiency of DSSC with
      sputtered Pt counter electrode (2.19%). The excellent photovoltaic performance,
      rapid and simple fabrication method and low-cost of the rGO@PPy can be
      potentially exploited as a alternative counter electrode to the expensive Pt in
      DSSCs.

PMID- 24930389
TI  - Gemcitabine, capecitabine and oxaliplatin in advanced biliary tract carcinoma.

PMID- 24930388
TI  - Assessing the discordance rate between local and central HER2 testing in women
      with locally determined HER2-negative breast cancer.
AB  - BACKGROUND: The importance of human epidermal growth factor receptor 2 (HER2) as
      a prognostic and predictive marker in invasive breast cancer is well established.
      Accurate assessment of HER2 status is essential to determine optimal treatment
      options. METHODS: Breast cancer tumor tissue samples from the VIRGO observational
      cohort tissue substudy that were locally HER2-negative were retested centrally
      with both US Food and Drug Administration (FDA)-approved immunohistochemistry
      (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved
      assay cutoffs; results were compared. RESULTS: Of the 552 unique patient samples
      centrally retested with local HER2-negative results recorded, tumor samples from
      22 (4.0%) patients were determined to be HER2-positive (95% confidence interval
      [CI] = 2.5%-5.7%). Of these, 18 had been tested locally by only one testing
      methodology; 15 of 18 were HER2-positive after the central retesting, based on
      the testing methodology not performed locally. Compared with the 530 patients
      with centrally confirmed HER2-negative tumors, the 22 patients with centrally
      determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years)
      and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These
      patients also had shorter median progression-free survival (6.4 months [95% CI =
      3.8-15.9 months] versus 9.1 months [95% CI = 8.3-10.3 months]) and overall
      survival (25.9 months [95% CI = 13.8-not estimable] versus 27.9 months [95% CI =
      25.0-32.9 months]). CONCLUSIONS: This study highlights the limitations of
      employing just one HER2 testing methodology in current clinical practice. It
      identifies a cohort of patients who did not receive potentially efficacious
      therapy because their tumor HER2-positivity was not determined by the test
      initially used. Because of inherent limitations in testing methodologies, it is
      inadvisable to rely on a single test to rule out potential benefit from HER2
      targeted therapy.

PMID- 24930390
TI  - Long-term results of intraoperative extracorporeal irradiation of autogenous bone
      grafts on primary bone and soft tissue malignancies.

PMID- 24930391
TI  - Primary orbital tumors: a review of 122 cases during a 23-year period: a histo
      clinical study in material from the ENT Department of the Medical University of
      Silesia.
AB  - BACKGROUND: The aim of this study was to investigate the distribution of
      different types of primary orbital tumors, histopathological diagnosis, and
      postoperative complications. MATERIAL AND METHODS: We analyzed 122 patients (68
      women and 54 men) with orbital tumors, hospitalized in the ENT Department of the
      Medical University of Silesia in Katowice during 1990-2013. The patients were
      characterized in terms of anatomic, topographical, histopathological, and
      clinical parameters. The role of diagnostic imagining such as CT, NMR, and fine
      needle aspiration (FNB) in preoperative diagnostics is discussed. RESULTS: of
      FNB, cytological, and histopathological examination of the postoperative
      specimens were compared. Results There were 56 (46%) patients with malignant
      tumors, 42 (34%) with benign tumors, 19 (16%) with inflammatory tumors, and 5
      patients (4%) had other tumors. In cases of malignant tumors, local recurrence up
      to 5 years was found in 36 (64.3%) cases. In the other 20 (35.7%) cases of
      malignant tumors, the patients remained under close follow-up in the outpatient
      clinic, without signs of local recurrence (follow-up 1-17 years). According to
      histopathological examination, malignant tumors were detected in 45.9% of
      patients and non-malignant tumor in 34.4% of patients. In 19.7% of patients,
      inflammatory and other types of tumors were diagnosed. CONCLUSIONS: We
      characterized the occurrence and pathological profiles of orbital tumors. The
      tumor location, histopathological diagnosis, and postoperative complications give
      us important information for the diagnosis of tumor prior to biopsy or tumor
      resection and for the determination of the treatment strategy and possible
      complications after surgery.

PMID- 24930392
TI  - Modulation of imatinib cytotoxicity by selenite in HCT116 colorectal cancer
      cells.
AB  - Imatinib is a principal therapeutic agent for targeting colorectal tumours.
      However, mono-targeting by imatinib does not always achieve complete cancer
      eradication. Selenite, a well-known chemopreventive agent, is commonly used in
      cancer patients. In this study, we aimed to explore whether selenite can modulate
      imatinib cytotoxicity in colorectal cancer cells. HCT116 cells were treated with
      different concentrations of imatinib and/or selenite for 24, 48 and 72 hr.
      Imatinib-selenite interaction was analysed using isobologram equation. As
      indicators of apoptosis, DNA fragmentation, caspase-3 activity, Bcl-2 expression
      were explored. Autophagic machinery was also checked by visualizing acidic
      vesicular organelles and measuring Beclin-1 expression. Furthermore, reactive
      oxygen and nitrogen species were also examined. This study demonstrated that
      selenite synergistically augmented imatinib cytotoxicity in HCT116 cells as
      demonstrated by combination and dose reduction indices. Supranutritional dose of
      selenite when combined with imatinib induced apoptotic machinery by decreasing
      Bcl-2 expression, increasing caspase-3 activity and subsequently fragmenting DNA
      and blunted cytoprotective autophagy by decreasing Beclin-1 expression and
      autophagosomes formation. Moreover, their combination induced cell cycle S-phase
      block, increased total thiol content and reduced nitric oxide levels. In
      conclusion, selenite synergizes imatinib cytotoxicity through multi-barrelled
      molecular targeting, providing a novel therapeutic approach for colorectal
      cancer. 

PMID- 24930393
TI  - Size-dependent property and cell labeling of semiconducting polymer dots.
AB  - Semiconducting polymer dots (Pdots) represent a new class of fluorescent
      nanoparticles for biological applications. In this study, we investigated their
      size-dependent fluorescence and cellular labeling properties. We demonstrate that
      the polymer conformation in solution phase largely affects the polymer folding
      and packing during the nanoparticle preparation process, resulting in solution
      phase control over the fluorescence properties of semiconducting polymer
      nanoparticles. The resulting Pdots exhibit apparent size dependent absorption and
      emission, a characteristic feature of different chain packing behaviors due to
      the preparation conditions. Single-particle fluorescence imaging was employed to
      perform a side-by-side comparison on the Pdot brightness, indicating a quadratic
      dependence of single-particle brightness on particle size. Upon introducing a
      positively charged dye Nile blue, all the three type of Pdots were quenched very
      efficiently (Ksv > 1 * 10(7) M(-1)) in an applied quenching process at low dye
      concentrations, but exhibit apparent difference in quenching efficiency with
      increasing dye concentration. Furthermore, Pdots of different sizes were used for
      cell uptake and cellular labeling involving biotin-streptavidin interactions.
      Fluorescence imaging together with flow cytometry studies clearly showed size
      dependent labeling brightness. Small-sized Pdots appear to be more effective for
      immunolabeling of cell surface, whereas medium-sized Pdots exhibit the highest
      uptake efficiency. This study provides a concrete guidance for selecting
      appropriate particle size for biological imaging and sensing applications. 

PMID- 24930394
TI  - Directional relationships between alcohol use and antisocial behavior across
      adolescence.
AB  - BACKGROUND: The co-occurrence of alcohol use and antisocial behavior is well
      established, but different hypotheses exist regarding the direction of effects
      between the 2 behaviors. We used longitudinal data to examine the directional
      relationship between the 2 behaviors across adolescence. METHODS: A cross-lagged
      model was applied to longitudinal data from the Avon Longitudinal Study of
      Parents and Children. The sample used in the present study consisted of 4,354
      females and 3,984 males. Alcohol use and antisocial behavior were measured with
      multiple items collected at 12, 13, 15, and 17 years of age. RESULTS: Both
      alcohol use and antisocial behavior were highly stable, as evidenced by highly
      significant autoregressive paths. Regarding the cross-lagged paths, neither
      behavior was predictive of the other during early adolescence (between ages 12
      and 13). During mid-to late adolescence (from ages 13 to 17), antisocial behavior
      was predictive of subsequent alcohol use. Alcohol use was predictive of
      antisocial behavior in late adolescence (between ages 15 and 17), although this
      relationship was mainly driven by males and was not significant in the female
      subgroup. CONCLUSIONS: The result generally supported the direction from
      antisocial behavior to alcohol use, especially during mid- to late adolescence.
      However, there was also a suggestion that the direction of relationship between
      the 2 behaviors changes across adolescence. The results highlight the importance
      of considering developmental stages to understand the directional relationships
      between the 2 behaviors.

PMID- 24930396
TI  - Unique and conserved features of floral evocation in legumes.
AB  - Legumes, with their unique ability to fix atmospheric nitrogen, play a vital role
      in ensuring future food security and mitigating the effects of climate change
      because they use less fossil energy and produce less greenhouse gases compared
      with N-fertilized systems. Grain legumes are second only to cereal crops as a
      source of human and animal food, and they contribute approximately one third of
      the protein consumed by the human population. The productivity of seed crops,
      such as grain legumes, is dependent on flowering. Despite the genetic variation
      and importance of flowering in legume production, studies of the molecular
      pathways that control flowering in legumes are limited. Recent advances in
      genomics have revealed that legume flowering pathways are divergent from those of
      such model species as Arabidopsis thaliana. Here, we discuss the current
      understanding of flowering time regulation in legumes and highlight the unique
      and conserved features of floral evocation in legumes. 

PMID- 24930397
TI  - Biofilm production by Zymomonas mobilis enhances ethanol production and tolerance
      to toxic inhibitors from rice bran hydrolysate.
AB  - Microorganisms play a significant role in bioethanol production from
      lignocellulosic material. A challenging problem in bioconversion of rice bran is
      the presence of toxic inhibitors in lignocellulosic acid hydrolysate. Various
      strains of Zymomonas mobilis (ZM4, TISTR 405, 548, 550 and 551) grown under
      biofilm or planktonic modes were used in this study to examine their potential
      for bioconversion of rice bran hydrolysate and ethanol production efficiencies.
      Z. mobilis readily formed bacterial attachment on plastic surfaces, but not on
      glass surfaces. Additionally, the biofilms formed on plastic surfaces steadily
      increased over time, while those formed on glass were speculated to cycle through
      accumulation and detachment phases. Microscopic analysis revealed that Z. mobilis
      ZM4 rapidly developed homogeneous biofilm structures within 24 hours, while other
      Z. mobilis strains developed heterogeneous biofilm structures. ZM4 biofilms were
      thicker and seemed to be more stable than other Z. mobilis strains. The
      percentage of live cells in biofilms was greater than that for planktonic cells
      (54.32 +/- 7.10% vs. 28.69 +/- 3.03%), suggesting that biofilms serve as a
      protective niche for growth of bacteria in the presence of toxic inhibitors in
      the rice bran hydrolysate. The metabolic activity of ZM4 grown as a biofilm was
      also higher than the same strain grown planktonically, as measured by ethanol
      production from rice bran hydrolysate (13.40 +/- 2.43 g/L vs. 0.432 +/- 0.29 g/L,
      with percent theoretical ethanol yields of 72.47 +/- 6.13% and 3.71 +/- 5.24%
      respectively). Strain TISTR 551 was also quite metabolically active, with ethanol
      production by biofilm and planktonically grown cells of 8.956 +/- 4.06 g/L and
      0.0846 +/- 0.064 g/L (percent theoretical yields were 48.37 +/- 16.64% and 2.046
      +/- 1.58%, respectively). This study illustrates the potential for enhancing
      ethanol production by utilizing bacterial biofilms in the bioconversion of a
      readily available and normally unusable low value by-product of rice farming.

PMID- 24930398
TI  - Myelin paucity of the superior cerebellar peduncle in individuals with Friedreich
      ataxia: an MRI magnetization transfer imaging study.
AB  - The dentate nucleus (DN) is the major relay station for neural connection between
      the cerebellum and cerebrum via the thalamus, and is a significant component of
      the neuropathological profile of Friedreich ataxia (FRDA). We have previously
      shown that the size of the superior cerebellar peduncle (SCP), which links the DN
      to cortical and subcortical structures via the thalamus, is significantly reduced
      in individuals with FRDA compared to control participants. This study used
      magnetization transfer imaging (MTI) to examine and contrast the integrity of
      white matter (WM) in the SCP and the corpus callosum (CC) (control region) in ten
      individuals with FRDA and ten controls. Individuals with FRDA demonstrated a
      significant reduction in the magnetization transfer ratio (MTR) in the SCP
      compared to control participants. However, there was no significant difference
      between groups in MTR in the CC. When comparing regions within groups, there was
      a significant reduction in MTR in the SCP compared to CC in participants with
      FRDA only. We suggest that the reduction in MTR in the SCP may be indicative of
      lack of myelin secondary to axonal loss and oligodendroglial dysfunction in WM
      tracts in individuals with FRDA. 

PMID- 24930395
TI  - Structure of the mammalian ribosome-Sec61 complex to 3.4 A resolution.
AB  - Cotranslational protein translocation is a universally conserved process for
      secretory and membrane protein biosynthesis. Nascent polypeptides emerging from a
      translating ribosome are either transported across or inserted into the membrane
      via the ribosome-bound Sec61 channel. Here, we report structures of a mammalian
      ribosome-Sec61 complex in both idle and translating states, determined to 3.4 and
      3.9 A resolution. The data sets permit building of a near-complete atomic model
      of the mammalian ribosome, visualization of A/P and P/E hybrid-state tRNAs, and
      analysis of a nascent polypeptide in the exit tunnel. Unprecedented chemical
      detail is observed for both the ribosome-Sec61 interaction and the conformational
      state of Sec61 upon ribosome binding. Comparison of the maps from idle and
      translating complexes suggests how conformational changes to the Sec61 channel
      could facilitate translocation of a secreted polypeptide. The high-resolution
      structure of the mammalian ribosome-Sec61 complex provides a valuable reference
      for future functional and structural studies. 

PMID- 24930399
TI  - Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative
      stress and up-regulating heme oxygenase-1 expression.
AB  - Oxidative stress is involved in the pathogenesis of Parkinson's disease (PD).
      Edaravone has been shown to have a neuroprotective effect. In the present work,
      we investigated the effect of edaravone on 1-methyl-4-phenylpyridinium (MPP(+))
      treated PC12 cells. Edaravone inhibited the decrease of cell viability and
      apoptosis induced by MPP(+) in PC12 cells. In addition, edaravone alleviated
      intracellular reactive oxygen species (ROS) production. MPP(+) induced heme
      oxygenase-1 (HO-1) expression, which was further enhanced by edaravone. The
      inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of
      edaravone. So edaravone protected PC12 cells against MPP(+)-cytoxicity via
      inhibiting oxidative stress and up-regulating HO-1 expression. The data showed
      that edaravone was neuroprotective and could be potentially therapeutics for PD
      in future. 

PMID- 24930400
TI  - Sixth nerve palsy associated with obstruction in Dorello's canal, accompanied by
      nodular type muscular sarcoidosis.
AB  - A 52-year-old Japanese woman complaining of horizontal double vision for 10 days
      was admitted to our hospital. Neurological examination revealed left abducent
      nerve palsy and muscle swelling in her thighs. Brain MRI showed obstruction in
      the spinal fluid space of the left Dorello's canal, which transmits a portion of
      the abducent nerve. In Ga-67-enhanced citrate scintigraphy, wide accumulation was
      seen in her bilateral thighs, lower legs, and gluteus muscles. Muscular MRI
      showed a star-shaped central structure on short tau inversion recovery (STIR)
      images, and the three stripes sign on T2-weighted images. These MRI findings
      indicated nodular-type muscular sarcoidosis. A muscle biopsy from the quadriceps
      femoris showed granulomatous epithelioid giant cells and non-necrotizing chronic
      lymphadenitis, which also indicate sarcoidosis. Her condition was considered to
      be caused by sarcoid granulomas obstructing Dorello's canal. She was treated with
      oral prednisolone (1 mg.kg(-1).day(-1)) and her symptoms and MRI findings
      improved. This is the first known report of abducent nerve impairment in
      Dorello's canal, other than fetal hypoplasia. Brain MRI, muscular MRI, and muscle
      biopsy are useful for the diagnosis of abducent nerve palsy, and it is important
      to consider Dorello's canal obstruction by sarcoidosis. Complete remission can be
      achieved with proper treatment.

PMID- 24930402
TI  - Unusual regio- and stereo-selectivity in Diels-Alder reactions between bulky N
      phenylmaleimides and anthracene derivatives.
AB  - Unusual regio- and stereo-selectivity in Diels-Alder (D-A) reactions were
      achieved between bulky N-phenylmaleimides and anthracene derivatives. Using
      multiple substituents with steric hindrance on both diene and dienophile, a
      noticeable shift toward 1,4-addition was successfully obtained. The substrate
      scope in this reaction was broad and the highest yield of anti-1,4-adducts was
      over 90%. Novel structures of anti-1,4-adducts were confirmed by single crystal X
      ray diffraction analysis. This study not only provides the first reported method
      of synthesizing anti-1,4-adducts and achieving otherwise unattainable regio- and
      stereo-selectivity, but also elucidates the importance of combining the steric
      effects of two reactants to shift products toward 1,4-adducts. Moreover, the
      resulting 1,4-adducts could be further functionalized through their halogen
      groups via carbon-carbon coupling reactions. 

PMID- 24930401
TI  - Differences in heterocycle basicity distinguish homocysteine from cysteine using
      aldehyde-bearing fluorophores.
AB  - We report the detection of homocysteine over cysteine based upon characteristic
      differences between 5- and 6-membered heterocyclic amines formed upon reaction
      with aldehyde-bearing compounds. Homocysteine-derived thiazinane-4-carboxylic
      acids are more basic than cysteine-derived thiazolidines-4-carboxylic acids.
      Fluorescence enhancement in response to homocysteine is achieved by tuning pH and
      excitation wavelength. 

PMID- 24930403
TI  - Combined two-photon excitation and d->f energy transfer in a water-soluble
      Ir(III)/Eu(III) dyad: two luminescence components from one molecule for cellular
      imaging.
AB  - The first example of cell imaging using two independent emission components from
      a dinuclear d/f complex is reported. A water-stable, cell-permeable Ir(III)
      /Eu(III) dyad undergoes partial Ir->Eu energy transfer following two-photon
      excitation of the Ir unit at 780 nm. Excitation in the near-IR region generated
      simultaneously green Ir-based emission and red Eu-based emission from the same
      probe. The orders-of-magnitude difference in their timescales (Ir ca. MUs; Eu ca.
      0.5 ms) allowed them to be identified by time-gated detection. Phosphorescence
      lifetime imaging microscopy (PLIM) allowed the lifetime of the Ir-based emission
      to be measured in different parts of the cell. At the same time, the cells are
      simultaneously imaged by using the Eu-based emission component at longer
      timescales. This new approach to cellular imaging by using dual d/f emitters
      should therefore enable autofluorescence-free sensing of two different analytes,
      independently, simultaneously and in the same regions of a cell. 

PMID- 24930405
TI  - A simple, robust and rapid approach to detect carbapenemases in Gram-negative
      isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem
      mass spectrometry, microarray and PCR.
AB  - Carbapenemases should be accurately and rapidly detected, given their possible
      epidemiological spread and their impact on treatment options. Here, we developed
      a simple, easy and rapid matrix-assisted laser desorption ionization-time of
      flight (MALDI-TOF)-based assay to detect carbapenemases and compared this
      innovative test with four other diagnostic approaches on 47 clinical isolates.
      Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount
      of antibiotic present in the supernatant after 1 h of incubation and both MALDI
      TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By
      comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103
      microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of
      Aeromonas were not detected because their chromosomal carbapenemase is not
      targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based
      approach that uses a stable 10-MUg disk of ertapenem was highly efficient in
      detecting carbapenemase, with a sensitivity higher than that of PCR and
      microarray. 

PMID- 24930406
TI  - Comment on "Surface-charge distribution on a dielectric sphere due to an external
      point charge: examples of C60 and C240 fullerenes, Phys. Chem. Chem. Phys., 2013,
      15, 20115".

PMID- 24930408
TI  - Editorial.

PMID- 24930409
TI  - Prescribing pattern and indicators for performance in a psychiatric practice.
AB  - AIMS To assess the prescribing pattern and to measure some specific aspects of
      the behaviour of the prescribers (psychiatrists) before and after educational
      interventions using core drug use indicators. METHODS In the present randomized
      retrospective controlled pre-post intervention prescription survey of
      schizophrenia and depression, 100 prescriptions each for schizophrenia and
      depression were obtained before and after each intervention. The prescriptions
      were analyzed for the following prescriber-specific indicators: number of drugs
      prescribed, prescribing by generic names, prescriptions for essential drugs,
      antiparkinsonian and benzodiazepines, nature of drugs and number of combinations
      prescribed. Based on the results of pre-intervention data, two interactional
      workshops were conducted 1 and 6 months after pre-intervention data collection.
      The first workshop focused on the results of the prescription audit feedback and
      reasons thereof. The second workshop focused, in addition, on appropriate
      management of schizophrenia and depression using consensus treatment guidelines
      with the aim of evolving a consensus on the treatment in a given hospital
      setting. RESULTS Before intervention, the essential drugs accounted for 80.95 and
      96.91% of the total number of drugs prescribed in depression and schizophrenia,
      respectively. Prescription for essential drugs improved further significantly in
      the post intervention period to 95.26% (P<0.04) for depression; whereas, in
      schizophrenia, prescriptions for essential drugs declined to 80.95%. The average
      number of drugs prescribed per encounter marginally declined in both
      schizophrenia (2.46+/-0.94 to 2.34+/-0.65) and depression (2.09+/-0.79 to 2.00+/
      0.65) after the second intervention. The patients receiving two or more drugs
      from the same group together declined from 12 to 9% in schizophrenia, but
      increased from 5 to 10% in depression after intervention. Trihexyphenidyl, an
      antiparkinsonian drug, was co-prescribed (90%) with antipsychotic agents (98%) in
      schizophrenia; however, use of benzodiazepines declined significantly after
      intervention to 28% compared to 48% in the pre-intervention period. Also,
      benzodiazepine use was high (68%) and remained so (70%) after interventions in
      depression cases. CONCLUSION The present study demonstrates excessive use of
      antiparkinsonian agents in schizophrenia and benzodiazepines in depression.
      Monitoring for the use of antiparkinsonian and benzodiazepines can form an
      important component for measuring specific aspects of prescriber's behaviour,
      which can be used as an indicator for comparisons at different time intervals and
      between health facilities. 

PMID- 24930407
TI  - Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy
      overcomes the effect of the ITPA gene polymorphism.
AB  - Treatment success of chronic hepatitis C virus genotype 1 infection has improved
      with the advent of telaprevir plus peg-interferon/ribavirin triple combination
      therapy. However, the effect of inosine triphosphatase (ITPA) polymorphism on
      dose reduction during triple therapy, especially during the postmarketing phase,
      has not been sufficiently evaluated. We analysed 273 patients with genotype 1
      infection who were treated with triple therapy and assessed the effect of the
      ITPA polymorphism on dose reduction. ITPA and IFNL4 SNP genotypes were determined
      by the Invader assay. A stepwise multivariate regression analysis was performed
      to identify factors associated with outcome of the therapy. The overall sustained
      viral response (SVR) rate 12 weeks after the end of therapy was 80.2% (219/273).
      Decline of haemoglobin was significantly faster, and ribavirin was more
      extensively reduced in patients with ITPA SNP rs1127354 genotype CC than CA/AA.
      Extensive reduction of ribavirin resulted in mild reduction of telaprevir and peg
      interferon, but no significant increase in viral breakthrough. Although the
      amount of telaprevir given was slightly higher in CA/AA patients, the total dose
      of peg-interferon and the SVR rate did not differ between the two groups.
      Multivariate analysis showed that IFNL4 but not ITPA SNP genotype, platelet count
      and peg-interferon adherence were significantly associated with outcome of
      therapy. Postmarketing-phase triple therapy resulted in a high SVR rate in spite
      of extensive ribavirin dose reduction in a diverse patient population, indicating
      the importance of treatment continuation and appropriate management of adverse
      events.

PMID- 24930410
TI  - Sexual assault on wards: Staff actions and reactions.
AB  - INTRODUCTION The aim of the study was to look at staff practices when patients
      had been sexually assaulted, and to look at their emotions around an event that
      normally causes outrage amongst those who deal with it. METHODS A 16-item, five
      point questionnaire was supplied to all medical and nursing staff working on five
      wards of a psychiatric inpatient unit. Demographic details of respondents and
      their work experience of sexual assault (defined as all forms of sexual touching
      without consent, including rape) were also noted. There were four additional
      questions inviting a free text response. Two questions were posed about inpatient
      sexuality in general, and two about sexual assault. RESULTS Staff generally
      agreed about what action should be taken in cases of sexual assault and, except
      for anger, experienced low levels of negative emotions when dealing with cases
      amongst patients. However, weariness was a key emotion, correlating with post
      held, levels of anger, depression, and likelihood of helping the patients inform
      the police. Consultants were the most weary professional group. Free text written
      responses revealed widespread concern amongst staff that women inpatients forming
      sexual relationships are vulnerable to exploitation and abuse, and that staff
      will be blamed in the event of sexual assault. CONCLUSION Policy documents should
      specifically address issues around staff intervention in inpatients' sexual
      lives. 

PMID- 24930411
TI  - Sex and segregation: Staff attitudes explored.
AB  - INTRODUCTION The aim of the study was to establish whether there was consistency
      of opinion amongst staff about mixed sex wards and the sexual activity of
      inpatients. Also to establish what demographic factors, if any, modulated those
      opinions. METHOD A 17-item, five-point, questionnaire was supplied to all medical
      and nursing staff working on five wards of a psychiatric inpatient unit.
      Demographic details of the respondents were also recorded. RESULTS Some items
      produced almost unanimous responses: 92.5% agreeing or strongly agreeing that
      some inpatients form sexually active relationships that are detrimental to their
      health. Staff felt that single sex wards should be available but were unsure that
      they would improve quality of life for either patients or staff. The strongest
      factor predicting response was profession (doctor or nurse), the responses being
      significantly different in eight of the 17 items. Doctors were more likely to
      believe that women's and staff's lives would be better on single sex wards and
      were less likely to be satisfied with current arrangements. They were also more
      likely to believe that sex was common among inpatients, and that there was an
      unofficial place to go in hospitals to have sex. Doctors worried more about the
      patient choice of sexual partner and believed that health workers should have a
      role in influencing that choice. Doctors also felt more strongly that patients
      sometimes form sexually active relationships of benefit to health. Ward was the
      next most important, being significantly different in four of the 17 questions.
      Gender and age of respondents produced few differences. CONCLUSIONS In view of
      the United Kingdom government commitment to phasing out mixed sex hospital
      accommodation by 2002 (Safety, privacy and dignity in mental health units -
      Guidance on mixed sex accommodation, Department of Health, 2000), the doubts of
      staff about improvement to inpatient quality of life, and their own quality of
      working life need to be further examined. Staff attitudes generally are more
      likely to be determined by job or ward of employment than the staff's gender,
      age, or experience of psychiatry. This may have implications in tailoring
      training schemes for staff of inpatient psychiatric units. 

PMID- 24930412
TI  - Comparison of escitalopram and citalopram efficacy: A meta-analysis.
AB  - OBJECTIVE Escitalopram is a new selective serotonin reuptake inhibitor (SSRI)
      indicated for the treatment of major depressive disorder (MDD) and panic
      disorder. Escitalopram is the therapeutically active enantiomer of citalopram.
      Its efficacy in the treatment of MDD was compared to that of citalopram. METHODS
      A quantitative meta-analysis was applied to 1262 patients in four randomised
      clinical trials; the comparison was based on response rate and mean change from
      baseline in the Montgomery-Asberg depression rating scale (MADRS) total score at
      week 8. Complementary analyses were performed on early MADRS change from baseline
      (week 1), in very severely depressed patients (baseline MADRS total score >=35)
      and on the influence of the level of severity at baseline. RESULTS Compared with
      citalopram, escitalopram-treated patients showed significantly higher response
      rates and increased mean change from baseline in MADRS at weeks 1 and 8. The
      superiority of escitalopram over citalopram was more pronounced in very severely
      depressed patients. This superiority was further shown to increase with degree of
      severity of the depression. The robustness of meta-analysis results was supported
      by sensitivity analyses. The clinical superiority of escitalopram versus
      citalopram is consistent with the results of preclinical pharmacological studies.
      CONCLUSION Escitalopram was shown to be an effective therapeutic treatment for
      MDD, presenting significant advantages over citalopram. 

PMID- 24930413
TI  - Major depressive disorder and response to citalopram treatment in women attending
      menopause clinic.
AB  - INTRODUCTION The authors investigated the prevalence of depressive disorders and
      response to citalopram among perimenopausal women visiting menopause clinics.
      METHOD One hundred and eighty-five consecutive outpatients were screened using
      the short Beck Depression Inventory. A psychiatrist investigated persons who
      showed medium or severe Beck depression. In the case of DSM-IV major depressive
      episode, a 6-week open trial with citalopram (20-40 mg daily) was started. The 17
      item Hamilton Depression Rating Scale (HDRS) measured the severity of depression
      at baseline and at weeks 3 and 6. The primary outcome measure was the rate of
      responders at weeks 3 and 6 (more than 50% drop in the total HDRS score at weeks
      3 and 6 compared to baseline). RESULTS Of the 185 consecutive outpatients
      screened, 48 (26%) have experienced medium or severe Beck depression, and 37 of
      them (20%) had DSM-IV major depression. Citalopram was started in 30 patients
      (daily doses ranged from 20 to 40 mg) and 21 (70%) finished the trial. The rate
      of responders at week 3 was 7/22 (32%) and at week 6 was 13/21 (62%). CONCLUSIONS
      Depressive disorders are common among perimenopausal women visiting menopause
      clinics, and the majority of those with depression respond well to citalopram.
      Interdisciplinary cooperation is the key point of the detection and follow up of
      these patients. 

PMID- 24930414
TI  - Symptomatic hypotension with venlafaxine-benzodiazepine interaction.
AB  - Venlafaxine is an effective antidepressant drug that is chemically distinct from
      other antidepressants. Alprazolam is a triazolobenzodiazepine and diazepam is a 2
      ketobenzodiazepine. Benzodiazepines are frequently co-administered with
      antidepressants, a fact that brings the problem of drug-drug interactions,
      because they are metabolized by various cytochrome pigment (CYP) 450 isoenzymes.
      We present three cases who developed symptomatic hypotension with co
      administration of venlafaxine and benzodiazepines, namely, alprazolam and
      diazepam. In all cases, arterial blood pressure returned to normal with the
      discontinuation of pharmacological treatment. Although there is insufficient
      evidence, a substantial inhibition of CYP 3A3/4 by venlafaxine could result in a
      meaningful increase in plasma levels of venlafaxine, O-desmethylvenlafaxine,
      alprazolam and diazepam, particularly in patients who are CYP 2D6 deficient. A
      less likely explanation for the interaction between venlafaxine and
      benzodiazepines would be CYP 3A3/4 deficiency, which might potentiate the
      increase in plasma levels of benzodiazepines, thereby increasing their adverse
      effect potential. Combination of venlafaxine and benzodiazepines may increase the
      incidence and severity of adverse effects of both drugs. 

PMID- 24930415
TI  - Granulocytopenia associated with neuroleptic therapy in a patient with benign
      familial leukopenia.
AB  - Benign familial leukopenia (BFL) has been reported in several ethnic groups,
      including Ethiopians of Jewish origin. To date, there are no reported cases of
      patients with BFL developing granulocytopenia following administration of
      neuroleptics. We report a case of a young Ethiopian Jew suffering from
      schizophrenia, who exhibited premorbid benign reduced white blood cells (WBC)
      count and developed leukopenia and neutropenia following exposure to typical
      (zuclopentixol, perphenazine, haloperidol) antipsychotics and the atypical
      antipsychotic risperidone. The diagnosis of BFL was established and tissue typing
      of the patient was determined. To the best of our knowledge, this is the first
      report of leukopenia with neutropenia in an ethnically susceptible (due to BFL)
      schizophrenia patient following exposure to typical and atypical antipsychotics.
      HLA typing of this patient was distinct from that reported in patients
      susceptible to clozapine-induced agranulocytosis. Further extensive
      investigations including HLA typing in a larger cohort of schizophrenic patients
      is needed in order to define the association between HLA haplotypes and
      neuroleptic-induced hematological reactions and to identify the potentially
      vulnerable individuals. 

PMID- 24930421
TI  - Speaker abstracts.

PMID- 24930416
TI  - Safety of fluoxetine treatment in a case of acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is a metabolic disease characterized by
      recurrent attacks of neurological and psychiatric dysfunction. It is a rare
      disorder of heme metabolism that usually presents with abdominal pain,
      gastrointestinal symptoms and autonomic nervous system disturbances. Exposure to
      certain drugs, dieting, starvation and infection during pregnancy may precipitate
      AIP attacks. Psychiatric manifestations of AIP include mood changes, organic
      brain syndrome and psychosis. Here, we present a 21-year-old female patient with
      AIP and major depression. She had a caesarean section under general anesthesia
      with pentothal and her recovery time from anesthesia took longer than usual. She
      had a blood transfusion because of severe anemia following the operation. Three
      days after her discharge she was readmitted to the hospital with confusion and
      seizure. It was her first AIP attack and it started 6 days after caesarean
      section. Two months after her first attack, we saw her for anxiety and depressive
      symptoms. She was in severe anxiety and depression and she was put on fluoxetine
      (20 mg/day liquid form). Following the treatment she did not develop any other
      porphyria attack. Her symptoms vanished and she improved functionally. She stayed
      on fluoxetine for 6 months without any new AIP attack. Despite limited data
      regarding fluoxetine therapy in porphyria patients, it seems to be safe for the
      treatment of depressive and anxiety symptoms in these patients. 

PMID- 24930422
TI  - The use of the Simpson Angus Scale for the assessment of movement disorder: A
      training guide.
AB  - The Simpson Angus Scale is commonly used for the assessment of Parkinsonian
      Movement Disorder related to psychiatric drug treatment. The authors present a
      practical guide to the use of the scale to assist both the learner and the
      teacher. 

PMID- 24930423
TI  - Thyroid imaging reporting and data system score combined with Bethesda system for
      malignancy risk stratification in thyroid nodules with indeterminate results on
      cytology.
AB  - CONTEXT: The thyroid imaging reporting and data system (TI-RADS) was designed to
      better select patients who had undergone fine-needle aspiration biopsies (FNABs)
      with high sensitivity and accuracy. However, the combination of TI-RADS scores
      and Bethesda system categories in indeterminate thyroid nodules has not been
      examined extensively. OBJECTIVE: This study aimed to stratify indeterminate
      thyroid nodules (Bethesda categories III, IV and V) according to risk of
      malignancy as determined by combining TI-RADS score with Bethesda system
      classification. DESIGN: Retrospective study. Histopathological, cytological and
      ultrasound (US) data were available for 242 cases after surgery, including 136
      indeterminate nodules. METHODS: All thyroid cytopathological slides and US
      reports were reviewed and classified according to Bethesda system and TI-RADS
      categories. The malignancy rate was determined for each Bethesda category, TI
      RADS score and both methods combined of indeterminate nodules. RESULTS: The
      malignancy rates were 8.7%, 51.3% and 67.5% for Bethesda categories III, IV and
      V, respectively. Based on histopathological comparison, the accuracy was 66.7%
      for TI-RADS greyscale. TI-RADS 3 and 4A scores were observed in 80% of Bethesda
      III cases, which led to 80% sensitivity and 90% of negative predictive value
      (NPV). In contrast, for nodules scored as TI-RADS 4B and 5, the combined
      cytological results of Bethesda IV and V resulted in a higher risk of malignancy
      (75% and 76.9%, respectively, P < 0.001). CONCLUSIONS: In view of the high NPV of
      TI-RADS 3/4A only in Bethesda III category, a surgical approach could be
      considered for lesions defined as Bethesda III, IV and V when TI-RADS 4B and 5
      were concomitant.

PMID- 24930424
TI  - Separation and identification of anthocyanin extracted from mulberry fruit and
      the pigment binding properties toward human serum albumin.
AB  - Purple pigments were isolated from mulberry extracts using preparative high-speed
      countercurrent chromatography (HSCCC) and identified by ESI-MS/MS and high
      performance liquid chromatography (HPLC) techniques. The solvent system
      containing methyl tert-butyl ether, 1-butanol, acetonitrile, water, and
      trifluoroacetic acid (10:30:10:50:0.05; %, v/v) was developed in order to
      separate anthocyanins with different polarities. Cyanidin 3-O-(6"-O-alpha
      rhamnopyranosyl-beta-galactopyranoside) (also known as keracyanin) is the major
      component present in mulberry (41.3%). Other isolated pigments are cyanidin 3-O
      (6"-O-alpha-rhamnopyranosyl-beta-glucopyranoside) and petunidin 3-O-beta
      glucopyranoside. The binding characteristics of keracyanin with human serum
      albumin (HSA) were investigated by fluorescence and circular dichroism (CD)
      spectroscopy. Spectroscopic analysis reveals that HSA fluorescence quenched by
      keracyanin follows a static mode. Binding of keracyanin to HSA mainly depends on
      van der Waals force or H-bonds with average binding distance of 2.82 nm. The
      results from synchronous fluorescence, three-dimensional fluorescence, and CD
      spectra show that adaptive structure rearrangement and decrease of alpha-helical
      structure occur in the presence of keracyanin. 

PMID- 24930425
TI  - Syringe disposal among people who inject drugs in Los Angeles: the role of
      sterile syringe source.
AB  - BACKGROUND: Few recent studies have investigated the prevalence of improperly
      discarded syringes in community settings by people who inject drugs (PWID). We
      examined whether syringe source was associated with the act of improper syringe
      disposal and amount of syringes improperly disposed of among PWID in Los Angeles,
      California. METHODS: A cross-sectional sample of PWID (N=412) was recruited and
      administered a structured questionnaire between July 2011 and April 2013.
      Descriptive analyses investigated syringe access and disposal practices among
      participants. Multivariate logistic regression analysis identified adjusted
      associations between syringe source (syringe exchange program [SEP] or pharmacy)
      and improper syringe disposal. RESULTS: Most participants were male (69%),
      homeless (62%) and low-income earners (64%). The majority (87%) of the sample
      received syringes from a SEP in the past six months, with 26% having received
      syringes from pharmacies and 36% from unauthorised sources (e.g., friend, drug
      dealer). Of more than 30,000 used syringes reportedly disposed of by participants
      during the past 30 days, 17% were disposed of improperly. Two percent of
      participants disposed of any used syringes at pharmacies, compared to 68% who
      used SEPs for syringe disposal. Having received sterile syringes from a SEP was
      independently associated with lower odds of improper syringe disposal; however,
      purchasing sterile syringes from pharmacies was associated with significantly
      higher odds of improper syringe disposal. CONCLUSION: In a city with both SEPs
      and pharmacies as syringe source and disposal options for PWID, these findings
      suggest that while pharmacies are selling syringes, they are not as readily
      involved in safe syringe disposal. Given limits on SEP availability and the large
      geographic size of Los Angeles County, augmenting current SEP services and
      providing other community disposal sites, including pharmacy disposal, processes
      could reduce improper syringe disposal among PWID in Los Angeles.

PMID- 24930427
TI  - Formal [4+2]-annulation of vinyl azides with N-unsaturated aldimines.
AB  - Highly functionalized quinolines and pyridines could be synthesized by BF3?OEt2
      mediated reactions of vinyl azides with N-aryl and N-alkenyl aldimines,
      respectively. The reaction mechanism could be characterized as formal [4+2]
      annulation, including unprecedented enamine-type nucleophilic attack of vinyl
      azides to aldimines and subsequent nucleophilic cyclization onto the resulting
      iminodiazonium ion moieties.

PMID- 24930426
TI  - Spatial gene expression analysis in tomato hypocotyls suggests cysteine as key
      precursor of vascular sulfur accumulation implicated in Verticillium dahliae
      defense.
AB  - Verticillium dahliae is a prominent generator of plant vascular wilting disease
      and sulfur (S)-enhanced defense (SED) mechanisms contribute to its in-planta
      elimination. The accumulation of S-containing defense compounds (SDCs) including
      elemental S (S(0) ) has been described based on the comparison of two near
      isogenic tomato (Solanum lycopersicum) lines differing in fungal susceptibility.
      To better understand the effect of S nutrition on V. dahliae resistance both
      lines were supplied with low, optimal or supraoptimal sulfate-S. An absolute
      quantification demonstrated a most effective fungal elimination due to luxury
      plant S nutrition. High-pressure liquid chromatography (HPLC) showed a strong
      regulation of Cys levels and an S-responsive GSH pool rise in the bulk hypocotyl.
      High-frequency S peak accumulations were detected in vascular bundles of
      resistant tomato plants after fungal colonization by laser ablation-inductively
      coupled plasma-mass spectrometry (LA-ICP-MS). Global transcriptomic analysis
      suggested that early steps of the primary S metabolism did not promote the SDCs
      synthesis in the whole hypocotyl as gene expression was downregulated after
      infection. Enhanced S fertilization mostly alleviated the repressive fungal
      effect but did not reverse it. Upregulation of glutathione (GSH)-associated genes
      in bulk hypocotyls but not in vascular bundles indicated a global antioxidative
      role of GSH. To finally assign the contribution of S metabolism-associated genes
      to high S(0) accumulations exclusively found in the resistant tomato line, a
      spatial gene expression approach was applied. Laser microdissection of infected
      vascular bundles revealed a switch toward transcription of genes connected with
      cysteine (Cys) synthesis. The upregulation of LeOASTLp1 suggests a role for Cys
      as key precursor for local S accumulations (possibly S(0) ) in the vascular
      bundles of the V. dahliae-resistant tomato line. 

PMID- 24930428
TI  - Rate of low vitamin D levels in a low-risk obstetric population.
AB  - INTRODUCTION: The objectives of this study were to determine vitamin D levels at
      the first prenatal visit in women who had no obstetric risk factors and, if
      determined to have a low vitamin D level, to evaluate how high-dose treatment
      affected the vitamin D level by the end of the second trimester. METHODS: This
      study was a descriptive, retrospective chart review. Women were identified
      through electronic database query based on prenatal care initiation. One hundred
      and four women had a 25-hydroxy (OH) vitamin D (25[OH]D) serum level drawn at the
      first prenatal visit. Supplementation was recommended with either 2000 or 4000
      units of vitamin D3 for women who had vitamin D insufficiency or deficiency.
      Twenty women who were treated had repeat vitamin D levels drawn at 28 weeks'
      gestation to evaluate the effectiveness of supplementation. RESULTS: Descriptive
      analysis of demographic data of 104 women who had 25(OH)D levels drawn determined
      there were no significant differences between women who were vitamin D deficient
      or insufficient and those whose serum levels were in the sufficient range.
      Vitamin D serum levels revealed that 32 (30.8%) were sufficient (>30 ng/mL), 49
      (47.1%) were insufficient (20-29 ng/mL), and 23 (22.1%) were deficient (<20
      ng/mL). Twenty women had a repeat measure of 25(OH)D after supplementation, and
      there was a significant rise in vitamin D level (P < .001) with vitamin D3
      supplementation. However, women who took 4000 units had a higher mean rise (13.17
      ng/mL) in 25(OH)D than those taking 2000 units (8.79 ng/mL). Twelve of the women
      (60%) were still insufficient after supplementation with 2000 units of vitamin D3
      . DISCUSSION: This small sample of women demonstrates a significant degree of
      insufficiency and deficiency in this desert community where sunshine is
      plentiful. A larger study should be completed to determine ideal supplementation
      during pregnancy.

PMID- 24930430
TI  - Polyketide biosynthesis in dinoflagellates: what makes it different?
AB  - Dinoflagellates produce unique polyketides characterized by their size and
      complexity. The biosynthesis of a limited number of such metabolites has been
      reported, with studies largely hampered by the low yield of compounds and the
      severe scrambling of label in the isotopically-labeled precursors. Nonetheless,
      of the successful biosynthetic experiments that have been reported, many
      surprising and unique processes have been discovered. This knowledge has been
      accessed through a series of biochemical labeling studies, and while limited
      molecular genetic data has been amassed, it is still in the early stages of
      development. In an attempt to meet this challenge, this review has compared some
      of the biosynthetic processes with similar ones identified in other microbes such
      as bacteria and myxobacteria, with the idea that similar genes and enzymes are
      employed by dinoflagellates.

PMID- 24930429
TI  - Efficacy of depression treatments for immigrant patients: results from a
      systematic review.
AB  - BACKGROUND: The unprecedented rates of global migration present unique challenges
      to mental health services in migrant receiving countries to provide efficacious
      and culturally salient treatment for mental health conditions including
      depression. This review aimed to identify and evaluate the effectiveness of
      depression interventions specifically directed towards first-generation immigrant
      populations. METHODS: We conducted a systematic review of original research
      published between 2000 and 2013 that investigated depression interventions in
      first generation immigrants. RESULTS: Fifteen studies were included; the majority
      focused on Latino immigrants living in the United States (US). Twelve studies
      investigated the use of psychotherapies; the remainder examined collaborative
      care models and physical exercise-based interventions. Cognitive Behavioral
      Therapy and Behavioral Activation tended to improve depressive symptoms,
      especially when culturally adapted to suit clients while Problem Solving Therapy
      improved depressive symptomology with and without adaptations. Collaborative care
      and exercise did not significantly improve depressive symptoms. CONCLUSION:
      Depression may be effectively treated by means of psychotherapies, especially
      when treatments are culturally adapted. However the reviewed studies were limited
      due to methodological weaknesses and were predominantly undertaken in the US with
      Latino patients. To improve generalizability, future research should be
      undertaken in non-US settings, amongst diverse ethnic groups and utilize larger
      sample sizes in either randomized clinical trials or observational cohort
      studies.

PMID- 24930431
TI  - In vitro efficacy of cefovecin against anaerobic bacteria isolated from
      subgingival plaque of dogs and cats with periodontal disease.
AB  - Periodontal disease is a common disease of dogs and cats often requiring
      antimicrobial treatment as an adjunct to mechanical debridement. However, correct
      compliance with oral antimicrobial therapy in companion animals is often
      difficult. Cefovecin is a recently introduced veterinary cephalosporin that has
      demonstrated prolonged concentrations in extracellular fluid, allowing for dosing
      intervals of up to 14 days. Subgingival samples were collected from the oral
      cavity of 29 dogs and eight cats exhibiting grade 2 or grade 3 periodontal
      disease. Samples were cultivated on Wilkin Chalgrens agar and incubated in an
      anaerobic chamber for seven days. Selected anaerobic bacteria were isolated and
      identified to species level using 16S rRNA gene sequence analysis. Minimum
      inhibitory concentrations were determined for cefovecin and six additional
      antimicrobials using the agar dilution methodology recommended by the Clinical
      and Laboratory Standards Institute. The 65 clinical isolates were identified as
      Porphyromonas gulae (n = 45), Porphyromonas crevioricanis (n = 12), Porphyromonas
      macacae (n = 1), Porphyromonas cangingivalis (n = 1) Fusobacterium nucleatum (n =
      2), Fusobacterium russii (n = 1) and Solobacterium moorei (n = 3). This is the
      first report of S. moorei being isolated from companion animals with periodontal
      disease. All isolates were highly susceptible to cefovecin, with a MIC90 of
      <=0.125 MUg/ml. Conversely, different resistance rates to ampicillin, amoxicillin
      and erythromycin between isolates were detected. Cefovecin is thus shown to be
      effective in vitro against anaerobic bacteria isolated from dogs and cats with
      periodontal disease. 

PMID- 24930432
TI  - Production of recombinant botulism antigens: a review of expression systems.
AB  - Botulism is a paralytic disease caused by intoxication with neurotoxins produced
      by Clostridium botulinum. Despite their similar mechanism of action, the
      botulinum neurotoxins (BoNT) are classified in eight serotypes (A to H). As to
      veterinary medicine, the impact of this disease is essentially economic, since
      different species of production animals can be affected, especially by BoNT/C and
      D. In human health, botulism is feared in a possible biological warfare, what
      would involve mainly the BoNT/A, B, E and F. In both cases, the most effective
      way to deal with botulism is through prevention, which involves vaccination.
      However, the current vaccines against this disease have several drawbacks on
      their process of production and, besides this, can be dangerous to producers
      since it requires certain level of biosafety. This way, recombinant vaccines have
      been shown to be a great alternative for the development of vaccines against both
      animal and human botulism. All BoNTs have a 50-kDa light chain (LC) and a 100-kDa
      heavy chain (HC). The latter one presents two domains of 50 kDa, called the N
      terminal (HN) and C-terminal (HC) halves. Among these regions, the HC alone seem
      to confer the proper immune response against intoxication. Since innumerous
      studies describe the expression of these distinct regions using different
      systems, strategies, and protocols, it is difficult to define the best option for
      a viable vaccine production. Thereby, the present review describes the
      problematic of botulism and discusses the main advances for the viable production
      of vaccines for both human and veterinary medicine using recombinant antigens. 

PMID- 24930433
TI  - Timed regulation of P-element-induced wimpy testis-interacting RNA expression
      during rat liver regeneration.
AB  - Small noncoding RNAs comprise a growing family of molecules that regulate key
      cellular processes, including messenger RNA (mRNA) degradation, translational
      repression, and transcriptional gene silencing. P-element-induced wimpy testis
      (PIWI)-interacting RNAs (piRNAs) represent a class of small RNAs initially
      identified in the germline of a variety of species, where they contribute to
      maintenance of genome stability, and recently found expressed also in stem and
      somatic cells, where their role and responsiveness to physiopathological signals
      remain elusive. Here, we investigated piRNA expression in rat liver and its
      response to the stimuli exerted by regenerative proliferation of this organ.
      Quantitative polymerase chain reaction analysis identify in the liver the RNAs
      encoding PIWIL2/HILI, PIWIL4/HIWI2, and other components of the piRNA biogenesis
      pathways, suggesting that this is indeed functional. RNA sequencing before,
      during, and after the wave of cell proliferation that follows partial hepatectomy
      (PH) identified ~1,400 mammalian germline piRNAs expressed in rat liver,
      including 72 showing timed changes in expression 24-48 hours post-PH, a timing
      that corresponds to cell transition through the S phase, returning to basal
      levels by 168 hours, when organ regeneration is completed and hepatocytes reach
      quiescence. CONCLUSION: The piRNA pathway is active in somatic cells of the liver
      and is subject to regulation during the pathophysiological process of organ
      regeneration, when these molecules are available to exert their regulatory
      functions on the cell genome and transcriptome, as demonstrated by the
      identification of several liver mRNAs representing candidate targets of these
      regulatory RNAs.

PMID- 24930435
TI  - PAH concentrations in lake sediment decline following ban on coal-tar-based
      pavement sealants in Austin, Texas.
AB  - Recent studies have concluded that coal-tar-based pavement sealants are a major
      source of polycyclic aromatic hydrocarbons (PAHs) in urban settings in large
      parts of the United States. In 2006, Austin, TX, became the first jurisdiction in
      the U.S. to ban the use of coal-tar sealants. We evaluated the effect of Austin's
      ban by analyzing PAHs in sediment cores and bottom-sediment samples collected in
      1998, 2000, 2001, 2012, and 2014 from Lady Bird Lake, the principal receiving
      water body for Austin urban runoff. The sum concentration of the 16 EPA Priority
      Pollutant PAHs (?PAH16) in dated core intervals and surficial bottom-sediment
      samples collected from sites in the lower lake declined about 44% from 1998-2005
      to 2006-2014 (means of 7980 and 4500 MUg kg(-1), respectively), and by 2012-2014,
      the decline was about 58% (mean of 3320 MUg kg(-1)). Concentrations of ?PAH16 in
      bottom sediment from two of three mid-lake sites decreased by about 71 and 35%
      from 2001 to 2014. Concentrations at a third site increased by about 14% from
      2001 to 2014. The decreases since 2006 reverse a 40-year (1959-1998) upward
      trend. Despite declines in PAH concentrations, PAH profiles and source-receptor
      modeling results indicate that coal-tar sealants remain the largest PAH source to
      the lake, implying that PAH concentrations likely will continue to decline as
      stocks of previously applied sealant gradually become depleted. 

PMID- 24930436
TI  - Study of the usefulness of moisturizers on adherence of acne patients treated
      with adapalene.
AB  - The efficacy of adapalene for acne treatment has been established. However,
      because of local adverse reactions, a fair number of patients discontinue
      adapalene treatment before experiencing its effects. To examine the usefulness of
      moisturizers concomitant with adapalene on adherence to treatment and its
      therapeutic effects in patients, 100 patients with mild to severe acne vulgaris
      were randomly assigned to one of two groups: group A, in which patients received
      adapalene in combination with a moisturizer (heparinoid); or group B, in which
      treatment consisted of adapalene alone and was converted to combination therapy
      with a moisturizer if local adverse reactions occurred that made adherence to
      treatment difficult. After 4 weeks of treatment, we compared the proportion of
      patients who adhered to therapy until the end of week 4, the number of treatment
      dropouts, and changes in the number of inflammatory eruptions and comedones
      between the groups. All of the patients in group A and 70% in group B continued
      the initial therapy until the end of week 4. In group B, three patients withdrew
      their consent and one patient stopped attending follow-up visits. The treatment
      period with the initial therapy was significantly elongated by the concomitant
      use of a moisturizer. No adverse effect of the use of a moisturizer was observed
      on the number of comedones and inflammatory eruptions. The concomitant use of a
      moisturizer with adapalene from the beginning of treatment did not affect its
      therapeutic effects and helped to improve adherence to treatment with adapalene. 

PMID- 24930434
TI  - Cell-surface central nervous system autoantibodies: clinical relevance and
      emerging paradigms.
AB  - The recent discovery of several potentially pathogenic autoantibodies has helped
      identify patients with clinically distinctive central nervous system diseases
      that appear to benefit from immunotherapy. The associated autoantibodies are
      directed against the extracellular domains of cell-surface-expressed neuronal or
      glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The
      original descriptions of the associated clinical syndromes were phenotypically
      well circumscribed. However, as availability of antibody testing has increased,
      the range of associated patient phenotypes and demographics has expanded. This in
      turn has led to the recognition of more immunotherapy-responsive syndromes in
      patients presenting with cognitive and behavioral problems, seizures, movement
      disorders, psychiatric features, and demyelinating disease. Although antibody
      detection remains diagnostically important, clinical recognition of these
      distinctive syndromes should ensure early and appropriate immunotherapy
      administration. We review the emerging paradigm of cell-surface-directed antibody
      mediated neurological diseases, describe how the associated disease spectrums
      have broadened since the original descriptions, discuss some of the
      methodological issues regarding techniques for antibody detection and emphasize
      considerations surrounding immunotherapy administration. As these disorders
      continue to reach mainstream neurology and even psychiatry, more cell-surface
      directed antibodies will be discovered, and their possible relevance to other
      more common disease presentations should become more clearly defined.

PMID- 24930437
TI  - Keratins 8 and 18 are type II acute-phase responsive genes overexpressed in human
      liver disease.
AB  - BACKGROUND & AIMS: Keratins (Ks) 7, 8, 18 and 19 constitute important markers and
      modifiers of liver disease. In mice, K8 and K18 are stress inducible and a
      dysregulated K8 > K18 stoichiometry predisposes to formation of Mallory-Denk
      bodies (MDBs), i.e. aggregates characteristic of chronic liver disorders such as
      alcoholic liver disease (ALD). In our study, we analyse the expression and the
      regulation of keratins in context of human liver disease. METHODS: K7, K8, K18
      and K19 mRNA levels were determined in liver biopsies from patients with ALD, non
      alcoholic steatohepatitis (NASH), chronic hepatitis B (HBV), hepatitis C (HCV)
      and from control subjects. HepG2 and Hep3B cells were treated with IL-1beta, IL-6
      and TNF-alpha. Mice were injected with turpentine, an established IL-6 inducer.
      RESULTS: K7, K8 and K18 were 1.5- to 3-fold upregulated in livers of ALD and HCV
      patients with a more active disease, but not in HBV/NASH subjects, while K19 was
      significantly elevated in all analysed disorders. K8 and K18 expression displayed
      a strong correlation (r = 0.89), but dysregulated levels with the K8 > K18 state
      were seen in ALD. All keratins were overexpressed in subjects with moderate vs.
      minimal inflammation, while K7, K8 and K18 were upregulated in patients with
      advanced liver fibrosis. In HepG2/Hep3B cells, IL-6 treatment but not IL-1beta or
      TNF-alpha significantly increased K8 and K18 expression and elevated K18 levels
      were seen after turpentine injection. CONCLUSIONS: Keratins represent type II
      acute-phase responsive genes overexpressed in specific human liver disorders. A
      K8 > K18 state occurs in ALD and predisposes to MDB formation.

PMID- 24930438
TI  - Analysis of 129I in the soils of Fukushima Prefecture: preliminary reconstruction
      of 131I deposition related to the accident at Fukushima Daiichi Nuclear Power
      Plant (FDNPP).
AB  - Iodine-131 is one of the most critical radionuclides to be monitored after
      release from reactor accidents due to the tendency for this nuclide to accumulate
      in the human thyroid gland. However, there are not enough data related to the
      reactor accident in Fukushima, Japan to provide regional information on the
      deposition of this short-lived nuclide (half-life = 8.02 d). In this study we
      have focused on the long-lived iodine isotope, (129)I (half-life of 1.57 * 10(7)
      y), and analyzed it by accelerator mass spectrometry (AMS) for surface soil
      samples collected at various locations in Fukushima Prefecture. In order to
      obtain information on the (131)I/(129)I ratio released from the accident, we have
      determined (129)I concentrations in 82 soil samples in which (131)I
      concentrations were previously determined. There was a strong correlation (R(2) =
      0.84) between the two nuclides, suggesting that the (131)I levels in soil samples
      following the accident can be estimated through the analysis of (129)I. We have
      also examined the possible influence from (129m)Te on (129)I, and found no
      significant effect. In order to construct a deposition map of (131)I, we
      determined the (129)I concentrations (Bq/kg) in 388 soil samples collected from
      different locations in Fukushima Prefecture and the deposition densities
      (Bq/m(2)) of (131)I were reconstructed from the results. 

PMID- 24930439
TI  - Nodular cystic fat necrosis with calcification in a patient with juvenile
      dermatomyositis.
AB  - Nodular cystic fat necrosis is a rare, benign form of encapsulated fat necrosis
      with distinct histology, characterized by cystic fat necrosis with lipomembranous
      changes and, in later stages, calcification. We report the case of a 7-year-old
      child with juvenile dermatomyositis who presented with three asymptomatic, firm,
      mobile nodules on the arms and neck. Histology was consistent with nodular cystic
      fat necrosis with prominent calcification. This is an unusual presentation of
      this entity because it has never been previously reported in association with
      juvenile dermatomyositis. 

PMID- 24930440
TI  - Therapeutic targeting of c-Myc in T-cell acute lymphoblastic leukemia, T-ALL.
AB  - T-ALL patients treated with intensive chemotherapy achieve high rates of
      remission. However, frequent long-term toxicities and relapses into chemotherapy
      refractory tumors constitute major clinical challenges which could be met by
      targeted therapies. c-MYC is a central oncogene in T-ALL, prompting the
      exploration of the efficacy of MYC inhibitors such as JQ1 (BET-bromodomain
      inhibitor), and SAHA (HDAC inhibitor). Using a standardized ex vivo drug
      screening assay, we show here that JQ1 and SAHA show competitive efficiency
      compared to inhibitors of proteasome, PI3K/AKT/mTOR and NOTCH pathways, and
      synergize in combination with Vincristine. We also compared for the first time
      the in vivo relevance of such associations in mice xenografted with human primary
      T-ALLs. Our data indicate that although treatments combining JQ1 or SAHA with
      chemotherapeutic regimens might represent promising developments in T-ALL,
      combinations will need to be tailored to specific subgroups of responsive
      patients, the profiles of which still remain to be precisely defined. 

PMID- 24930441
TI  - Semaphorin 3E secreted by damaged hepatocytes regulates the sinusoidal
      regeneration and liver fibrosis during liver regeneration.
AB  - The liver has a remarkable capacity to regenerate after injury. Although the
      regulatory mechanisms of hepatocytic regeneration have been a subject of intense
      study, the dynamism of the sinusoids, specialized blood vessels in the liver,
      remains largely unknown. Transient activation of hepatic stellate cells and
      hepatic sinusoidal endothelial cells, which constitute the sinusoids, contributes
      to liver regeneration during acute injury, whereas their sustained activation
      causes liver fibrosis during chronic injury. We focused on understanding the
      association between damaged hepatocytes and sinusoidal regeneration or liver
      fibrogenesis using a carbon tetrachloride-induced liver injury mouse model.
      Damaged hepatocytes rapidly expressed semaphorin 3E (Sema3e), which induced
      contraction of sinusoidal endothelial cells and thereby contributed to activating
      hepatic stellate cells for wound healing. In addition, ectopic and consecutive
      expression of Sema3e in hepatocytes by the hydrodynamic tail-vein injection
      method resulted in disorganized regeneration of sinusoids and sustained
      activation of hepatic stellate cells. In contrast, liver fibrosis ameliorated in
      Sema3e-knockout mice compared with wild-type mice in a chronic liver injury
      model. Our results indicate that Sema3e, secreted by damaged hepatocytes, affects
      sinusoidal regeneration in a paracrine manner during liver regeneration,
      suggesting that Sema3e is a novel therapeutic target in liver fibrogenesis. 

PMID- 24930442
TI  - Maternal high-dose folic acid during pregnancy and asthma medication in the
      offspring.
AB  - PURPOSE: Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has
      been associated with an increased risk for childhood asthma. The effect of high
      dose folic acid (5 mg) advised to women at risk for having a child with neural
      tube defect has not been assessed so far. Our aim was to investigate the effect
      of dispensed high-dose folic acid during pregnancy and asthma medication in the
      offspring. METHODS: We used data from the pregnancy database IADB.nl, which
      contains pharmacy-dispensing data of mothers and children from community
      pharmacies in the Netherlands from 1994 until 2011. The dispension of asthma
      medication in children exposed in utero to high-dose folic acid was compared with
      children who were not exposed to this high dose. Incidence rate ratios (IRRs)
      with 95% confidence intervals (CIs) were calculated. RESULTS: In 2.9% (N = 913)
      of the 39,602 pregnancies in the database, the mother was dispensed high-dose
      folic acid. Maternal high-dose folic acid was associated with an increased rate
      of asthma medication among children: recurrent asthma medication IRR = 1.14
      (95%CI: 1.04-1.30) and recurrent inhaled corticosteroids IRR = 1.26 (95%CI: 1.07
      1.47). Associations were clustered on the mother and adjusted for maternal age,
      maternal asthma medication, and dispension of benzodiazepines during pregnancy.
      CONCLUSION: Almost 3% of the children were prenatally exposed to high-dose folic
      acid. This study suggests that supplementation of high-dose folic acid during
      pregnancy might increase the risk of childhood asthma.

PMID- 24930443
TI  - Cost of an acting intern: clinical productivity in the academic emergency
      department.
AB  - BACKGROUND: A few studies suggest that an increasing clinical workload does not
      adversely affect quality of teaching in the Emergency Department (ED); however,
      the impact of clinical teaching on productivity is unknown. OBJECTIVES: The
      primary objective of this study was to determine whether there was a difference
      in relative value units (RVUs) billed by faculty members when an acting
      internship (AI) student is on shift. Secondary objectives include comparing RVUs
      billed by individual faculty members and in different locations. METHODS: A
      matched case-control study design was employed, comparing the RVUs generated
      during shifts with an Emergency Medicine (EM) AI (cases) to shifts without an AI
      (controls). Case shifts were matched with control shifts for individual faculty
      member, time (day, swing, night), location, and, whenever possible, day of the
      week. Outcome measures were gross, procedural, and critical care RVUs. RESULTS:
      There were 140 shifts worked by AI students during the study period; 18 were
      unmatchable, and 21 were night shifts that crossed two dates of service and were
      not included. There were 101 well-matched shift pairs retained for analysis.
      Gross, procedural, and critical care RVUs billed did not differ significantly in
      case vs. control shifts (53.60 vs. 53.47, p=0.95; 4.30 vs. 4.27, p=0.96; 3.36 vs.
      3.41, respectively, p=0.94). This effect was consistent across sites and for all
      faculty members. CONCLUSIONS: An AI student had no adverse effect on overall,
      procedural, or critical care clinical billing in the academic ED. When matched
      with experienced educators, career-bound fourth-year students do not detract from
      clinical productivity.

PMID- 24930444
TI  - Do hemolyzed potassium specimens need to be repeated?
AB  - BACKGROUND: In the emergency department (ED), hyperkalemia in the presence of
      hemolysis is common. Elevated hemolyzed potassium levels are often repeated by
      emergency physicians to confirm pseudohyperkalemia and to exclude a life
      threatening true hyperkalemia. OBJECTIVES: We hypothesize that in patients with a
      normal renal function, elevated hemolyzed potassium, and normal electrocardiogram
      (ECG), there may not be a need for further treatment or repeat testing and
      increased length of stay. METHODS: Data were prospectively enrolled patients
      presenting to the ED from July 2011 to February 2012. All adult subjects who had
      a hemolyzed potassium level >= 5.5 mEq/dL underwent a repeat potassium level and
      ECG. The incidence of true hyperkalemia in this population was measured. RESULTS:
      A total of 45 patients were enrolled. The overall median age was 52 years (range
      25-83 years); 22 were female (49%). In patients with hyperkalemia on initial
      blood draw and glomerular filtration rate (GFR) >= 60 (n = 45), the negative
      predictive value was 97.8% (95% confidence interval [CI] 88.2-99.9%). When
      patients had hyperkalemia on initial blood draw, GFR >= 60, and a normal ECG (n =
      42), the negative predictive value was 100% (95% CI 93.1-100%). CONCLUSIONS: In
      the setting of hemolysis, GFR >= 60 mL/min in conjunction with a normal ECG is a
      reliable predictor of pseudohyperkalemia and may eliminate the need for repeat
      testing. In patients with a normal GFR who are otherwise deemed safe for
      discharge, our results indicate there is no need for repeat testing.

PMID- 24930445
TI  - Left-sided superior vena cava and venous hyperoxia masquerading as inadvertent
      carotid artery catheterization.
AB  - BACKGROUND: A persistent left-sided superior vena cava (PLSVC) is a rare, often
      asymptomatic, venous anomaly that may be first diagnosed during central venous
      catheterization. During chest radiograph interpretation, a PLSVC can be confused
      with inadvertent arterial catheterization. CASE REPORT: We describe the
      presentation of a 45-year-old man with end-stage liver disease who required
      central venous catheterization for treatment of septic shock. An aberrantly
      placed catheter noted on chest radiograph and an elevated central venous oxygen
      saturation gave the appearance of inadvertent carotid artery catheterization. WHY
      SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A persistent left-sided superior
      vena cava can masquerade as an inadvertent cannulation of the carotid artery
      during central line placement. It is important for emergency physicians to be
      aware of this possibility when evaluating a chest radiograph with an aberrantly
      placed catheter. Venous hyperoxia may further complicate attempts to
      differentiate between arterial and venous catheterization in patients with septic
      shock. After confirmatory tests, the emergency physician should consider removal
      of the catheter due to potential complications.

PMID- 24930447
TI  - Construction and characterization of a recombinant invertebrate iridovirus.
AB  - Chilo iridescent virus (CIV), officially named Insect iridescent virus 6 (IIV6),
      is the type species of the genus Iridovirus (family Iridoviridae). In this paper
      we constructed a recombinant CIV, encoding the green fluorescent protein (GFP).
      This recombinant can be used to investigate viral replication dynamics. We showed
      that homologous recombination is a valid method to make CIV gene knockouts and to
      insert foreign genes. The CIV 157L gene, putatively encoding a non-functional
      inhibitor of apoptosis (IAP), was chosen as target for foreign gene insertion.
      The gfp open reading frame preceded by the viral mcp promoter was inserted into
      the 157L locus by homologous recombination in Anthonomus grandis BRL-AG-3A cells.
      Recombinant virus (rCIV-Delta157L-gfp) was purified by successive rounds of
      plaque purification. All plaques produced by the purified recombinant virus
      emitted green fluorescence due to the presence of GFP. One-step growth curves for
      recombinant and wild-type CIV were similar and the recombinant was fully
      infectious in vivo. Hence, CIV157L can be inactivated without altering the
      replication kinetics of the virus. Consequently, the CIV 157L locus can be used
      as a site for insertion of foreign DNA, e.g. to modify viral properties for
      insect biocontrol. 

PMID- 24930448
TI  - A highly immunogenic fragment derived from Zaire Ebola virus glycoprotein elicits
      effective neutralizing antibody.
AB  - In order to produce polyvalent vaccines based on single rVSV vector, we
      investigated the immunogenicity, antibody neutralizing activity, and antigenic
      determinant domain of Zaire Ebola's fragment MFL (aa 393-556) that contains furin
      site and internal fusion loop. Both the recombinant protein and the recombinant
      plasmid of fragment MFL elicited high levels of antibody, similar to those of
      Zaire Ebola GP (ZGP). The MFL fragment of ZGP also elicited high levels of
      neutralizing antibody and induced moderate cellular immune response in mice, as
      revealed by the proliferation and cytokine secretion of splenocytes. Through the
      analysis of the induction of neutralizing antibody by pVAX1-based recombinant
      plasmids that expressed truncated fragments of MFL, we found that the domain
      containing the internal fusion loop and the furin site was the major contributor
      of fragment MFL's immunogenicity. Furthermore, the rVSV-based bivalent vaccine
      expressing Sudan Ebola GP (SGP) and MFL fragment elicited efficient cross
      immunity against ZGP and SGP with high levels of neutralizing antibody. Our
      results indicate that fragment MFL is an effective and novel antigen for the
      production of neutralizing antibody and polyvalent vaccines of Ebola virus. 

PMID- 24930450
TI  - Formation of octameric methylaluminoxanes by hydrolysis of trimethylaluminum and
      the mechanisms of catalyst activation in single-site alpha-olefin polymerization
      catalysis.
AB  - Hydrolysis of trimethylaluminum (TMA) leads to the formation of
      methylaluminoxanes (MAO) of general formula (MeAlO)n (AlMe3)m. The
      thermodynamically favored pathway of MAO formation is followed up to n=8, showing
      the major impact of associated TMA on the structural characteristics of the MAOs.
      The MAOs bind up to five TMA molecules, thereby inducing transition from cages
      into rings and sheets. Zirconocene catalyst activation studies using model MAO co
      catalysts show the decisive role of the associated TMA in forming the
      catalytically active sites. Catalyst activation can take place either by Lewis
      acidic abstraction of an alkyl or halide ligand from the precatalyst or by
      reaction of the precatalyst with an MAO-derived AlMe2(+) cation. Thermodynamics
      suggest that activation through AlMe2(+) transfer is the dominant mechanism
      because sites that are able to release AlMe2(+) are more abundant than Lewis
      acidic sites. The model catalyst system is demonstrated to polymerize ethene.

PMID- 24930449
TI  - Comparisons of five Saccharomyces cerevisiae strains for ethanol production from
      SPORL-pretreated lodgepole pine.
AB  - The performances of five yeast strains under three levels of toxicity were
      evaluated using hydrolysates from lodgepole pine pretreated by Sulfite
      Pretreatment to Overcome the Recalcitrance of Lignocelluloses (SPORL). The
      highest level of toxicity was represented by the whole pretreated biomass slurry,
      while intermediate toxicity was represented by the hydrolysate with partial
      loading of pretreatment spent liquor. The zero toxicity was represented using the
      enzymatic hydrolysate produced from thoroughly washed SPORL lodgepole pine
      solids. The results indicate that strains D5A and YRH400 can tolerate the whole
      pretreated biomass slurry to produce 90.1 and 73.5% theoretical ethanol yield.
      Strains Y1528, YRH403, and FPL450 did not grow in whole hydrolysate cultures and
      were observed to have lower ethanol productivities than D5A and YRH400 on the
      hydrolysate with intermediate toxicity. Both YRH400 and YRH403 were genetically
      engineered for xylose fermentation but were not able to consume xylose
      efficiently in hydrolysate.

PMID- 24930451
TI  - Can pegylated interferon alpha 2a cause development of thyroid disorders in
      patients with chronic hepatitis B?
AB  - INTRODUCTION: Hepatitis B virus infection is treated with pegylated (Peg)
      IFNalpha and nucleos(t)ide analogues. The disadvantages of PegIFNalpha include
      thyroid disorders. In this single-center study, the type, incidence and
      consequences of thyroid dysfunction in patients receiving PegIFNalpha due to
      chronic hepatitis B (CHB) were analyzed. PATIENTS AND METHODS: The analysis
      included 106 patients (80 males) with CHB, aged 20 - 58 years, treated with
      PegIFNalpha-2a at a dose of 180 MUg/week subcutaneously for 48 weeks. The levels
      of thyroid-stimulating hormone (TSH) and thyroid antibodies (TAbs) that is anti
      thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies were measured
      in all patients at baseline. Furthermore, TSH was measured every 3 months during
      treatment and for 12 months after completion of treatment. If the TSH level was
      abnormal, free thyroxine 4 levels and TAbs were measured. RESULTS: All patients
      started the therapy with normal TSH and TAb levels. In 99 patients, TSH levels
      remained normal throughout the therapy. Thyroid disorder occurred in seven
      patients (6.6%), six of whom developed hypothyroidism and one who developed
      hyperthyroidism. Thyroid dysfunction was diagnosed in six women and one man. TAbs
      (only TPOAbs) were found in two patients (1.88%). CONCLUSIONS: Thyroid disorder
      is a rare, though possible not transient, complication of IFN therapy in CHB
      patients.

PMID- 24930446
TI  - Coronavirus reverse genetic systems: infectious clones and replicons.
AB  - Coronaviruses (CoVs) infect humans and many animal species, and are associated
      with respiratory, enteric, hepatic, and central nervous system diseases. The
      large size of the CoV genome and the instability of some CoV replicase gene
      sequences during its propagation in bacteria, represent serious obstacles for the
      development of reverse genetic systems similar to those used for smaller positive
      sense RNA viruses. To overcome these limitations, several alternatives to more
      conventional plasmid-based approaches have been established in the last 13 years.
      In this report, we briefly review and discuss the different reverse genetic
      systems developed for CoVs, paying special attention to the severe acute
      respiratory syndrome CoV (SARS-CoV). 

PMID- 24930453
TI  - Hypoxic regulation of metabolism offers new opportunities for anticancer therapy.
AB  - Cancer metabolism now appears to be optimized for growth of tumor cells by having
      an increased reliance on non-oxidative processes. However, in order to exploit
      these findings clinically, we must determine the specific pathways and components
      that cancer cells rely on, but are dispensable for normal cells. Because tumors
      have the added stress of hypoxia, the metabolic response to low oxygen may
      represent such a tumor-specific metabolic program. 

PMID- 24930452
TI  - Analysis by high throughput sequencing of Specific Pathogen Free eggs.
AB  - Specific Pathogen Free (SPF) embryonated eggs are used for the production of many
      veterinary and human vaccines. We have used High Throughput Sequencing to screen
      allantoic fluids and embryos for the presence of encapsidated viral genomes and
      viral transcripts, respectively. SPF eggs from two different producers were
      tested. We evidenced sequences corresponding to known endogenous retroviruses and
      sequences of Avian Leukosis Virus, but no sequence that might suggest a
      productive infection of eggs with a virus even distant from known viruses. Our
      results strongly suggest that SPF eggs such as those used for this study
      represent a safe substrate for the production of vaccines. 

PMID- 24930454
TI  - Successful lung transplant in a child with cystic fibrosis and persistent
      Blastobotrys rhaffinosifermentans infection.
AB  - Fungal respiratory infections in patients with CF are a significant concern both
      pre- and post-lung transplantation (LTx). Fungal infection is associated with
      increased mortality post-LTx, and in the past decade, the prevalence of fungal
      colonization in Canadian pediatric patients with CF has increased. The emergence
      of novel fungal pathogens is particularly challenging to the transplant
      community, as little is known regarding their virulence and optimal management.
      We present a case of a successful double-lung transplant in a pediatric patient
      with CF who was infected pretransplantation with a novel yeast, Blastobotrys
      rhaffinosifermentans. This patient was treated successfully with aggressive
      antifungal therapy post-transplantation, followed by extended fungal prophylaxis.
      The significance of fungal colonization and infection in children with CF pre-
      and post-LTx is reviewed. 

PMID- 24930455
TI  - Dimensions and disorder specificity of impulsivity in pathological gambling.
AB  - Impulsivity is a core characteristic of pathological gambling (PG), even though
      the underlying structure and disorder specificity is unclear. This study aimed to
      explore different dimensions of impulsivity in a clinical sample including PG.
      Furthermore, we aimed to test which alterations of the impulsivity-related
      dimensions are disorder specific for PG. Participants were individuals diagnosed
      with PG (n=51) and two groups also characterized by various impulsive behaviors:
      an alcohol dependence (AD; n=45) and a Gilles de la Tourette syndrome (GTS; n=49)
      group. A healthy control (HC; n=53) group was recruited as comparison group. A
      comprehensive assessment was used including impulsivity-related and antipodal
      parameters of the Stop Signal Task, Stroop Task, Tower of London Task, Card
      Playing Task, Iowa Gambling Task and the Barratt Impulsiveness Scale-11.
      Principal axis factor analysis revealed four impulsivity-related dimensions that
      were labeled 'self-reported impulsivity', 'prepotent response impulsivity',
      'choice impulsivity' and 'motor impulsivity'. The PG group scored significantly
      higher on all four dimensions compared to the HC group. In contrast, the PG group
      did not differ on any of the dimensions from the AD or the GTS group, except for
      'choice impulsivity' where the PG group exhibited higher factor scores compared
      to the GTS group. Altogether, PG is associated with generally heightened
      impulsivity profiles compared to a HC group, which may be further used for
      intervention strategies. However, heightened scores in the impulsivity dimensions
      are not disorder specific for PG. Further research on shared or different
      underlying mechanisms of these overlapping impulsivity impairments is necessary. 

PMID- 24930456
TI  - Effects of essential oils from medicinal plants acclimated to Benin on in vitro
      ruminal fermentation of Andropogon gayanus grass.
AB  - BACKGROUND: Plants from West Africa commonly used in both human and veterinary
      medicine contain various secondary metabolites. However, their potential in
      mitigating ruminal methane production has not been explored. This study examined
      the effects of seven essential oils (EOs) from plants acclimated to Benin at four
      dosages (100, 200, 300 and 400 mg L(-1)), on in vitro rumen microbial
      fermentation and methane production using Andropogon gayanus grass as a
      substrate. RESULTS: Compared to control, Laurus nobilis (300-400 mg L(-1) ),
      Citrus aurantifolia (300-400 mg L(-1)) and Ocimum gratissimum (200-400 mg L(-1))
      decreased (P < 0.05) methane production (mL g(-1) DM) by 8.1-11.8%, 11.9-17.8%
      and 7.9-30.6%, respectively. Relative to the control, reductions in methane (mL
      g(-1) DM) of 11.4%, 13.5% and 14.2% were only observed at 400 mg L(-1) for
      Eucalyptus citriodora, Ocimum basilicum and Cymbopogon citratus, respectively.
      These EOs lowered methane without reducing concentrations of total volatile fatty
      acids or causing a shift from acetate to propionate production. All EOs (except
      M. piperita) reduced (P < 0.05) apparent dry matter (DM) disappearance of A.
      gayanus. CONCLUSIONS: The current study demonstrated that EOs from plants grown
      in Benin inhibited in vitro methane production mainly through a reduction in
      apparent DM digestibility.

PMID- 24930457
TI  - Improving long-term outcomes of kidney transplantation: The pressure is on.

PMID- 24930458
TI  - Recommendations for the paracetamol treatment nomogram and side effects of N
      acetylcysteine.
AB  - Treatment of paracetamol intoxication consists of administration of N
      acetylcysteine, preferably shortly after paracetamol ingestion. In most
      countries, the decision to treat patients with N-acetylcysteine depends on the
      paracetamol plasma concentration. In the literature, different arguments are
      given regarding when to treat paracetamol overdose. Some authors do not recommend
      treatment with N-acetylcysteine at low paracetamol plasma concentrations since
      unnecessary adverse effects may be induced. But no treatment with N
      acetylcysteine at higher paracetamol plasma concentrations may lead to
      unnecessary severe morbidity and mortality. In this review, we provide an
      overview on the severity and prevalence of adverse side effects after N
      acetylcysteine administration and the consequences these side effects may have
      for the treatment of paracetamol intoxication. The final conclusion is to
      continue using the guidelines of the Dutch National Poisons Information Centre
      for N-acetylcysteine administration in paracetamol intoxication.

PMID- 24930460
TI  - Practice, attitude and knowledge of Dutch paediatric oncologists regarding female
      fertility.
AB  - BACKGROUND: Chemotherapy and radiotherapy for childhood cancer can result in a
      decreased reproductive function. It is therefore important that paediatric
      oncologists discuss the possible impact of treatment on female fertility and
      available fertility preservation options with their patients. However, it is
      unknown what Dutch paediatric oncologists know about of the effect of cancer
      treatment on female fertility, whether or not they address this issue in clinical
      practice, what their attitudes are towards addressing fertility after cancer
      treatment and fertility preservation options, and to what extent they require
      additional information resources. METHODS: In this nationwide quantitative cross
      sectional study a survey was sent to all registered paediatric oncologists in the
      Netherlands (n=64). RESULTS: Thirty-seven paediatric oncologists participated
      (participation rate 58%). Fertility issues were discussed with patients and/or
      parents by 97%. Of the paediatric oncologists, 54-76% were aware of possibilities
      for fertility preservation; however only <25% reported a moderate or high
      confidence in their knowledge of these techniques. Paediatric oncologists stated
      that they had little resources to counsel their patients and 92% found
      educational resources not completely sufficient. CONCLUSION: Paediatric
      oncologists are well aware of the effect that cancer treatment may have on female
      fertility and their responsibility to counsel their patients and/or the parents
      on this issue. They do not (yet) possess the knowledge to sufficiently counsel
      these patients and, if needed, do not frequently refer them to a fertility
      specialist.

PMID- 24930459
TI  - Treatment efficacy of hypertension in kidney transplant recipients in the
      Netherlands.
AB  - BACKGROUND: Hypertension in kidney transplant recipients jeopardises graft and
      patient survival. Guidelines suggest blood pressure targets of <=130/80 mmHg and
      sodium intake <90 mmol/day. METHODS: Since the efficacy of antihypertensive
      treatment among kidney transplant recipients is unknown, we analysed data on
      office-based blood pressure and use of antihypertensive drugs from the
      Netherlands Organ Transplant Registry on 5415 kidney transplant recipients.
      Additionally, we studied dosages, prevalence of treatment-resistant hypertension
      and 24-hour sodium excretion in 534 kidney transplant recipients from our centre
      to explore possibilities for therapy optimisation. RESULTS: In patients
      registered in the Netherlands Organ Transplant Registry, median blood pressure
      was 134/80 mmHg (interquartile range 122-145/70-85). In 77.2%, the blood pressure
      was >=130/80 mmHg; of these patients 10.4% had no registered use, 30.0% used one
      and 25.9% used >=3 classes of antihypertensive agents. Parameters from our centre
      were comparable: 78.7% had a median blood pressure of >=130/80 mmHg of whom 14.5%
      had no registered use of antihypertensives and 26.4% used >=3 classes. Sub
      maximal dosages were prescribed in 74.0% of the kidney transplant recipients with
      a blood pressure of >=130/80 mmHg while using at least one antihypertensive
      agent. Treatment-resistant hypertension was present in 7.7%. Median 24-hour
      sodium excretion was 147 mmol/day (interquartile range 109-195). CONCLUSIONS:
      This study suggests that therapeutic optimisation of antihypertensive treatment
      in kidney transplant recipients is, in theory, frequently possible by
      intensifying pharmacological treatment and by providing more advice on dietary
      sodium restrictions.

PMID- 24930462
TI  - Bilateral dacryoadenitis as a presenting symptom of an extra-ocular disease.

PMID- 24930461
TI  - Cost of screening strategies for kidney disease before intravenous contrast
      administration.
AB  - PURPOSE: To assess whether selective use of estimated glomerular filtration rate
      (eGFR) in patients with risk factors for kidney disease is more cost-effective
      than measuring eGFR in all patients undergoing contrast-enhanced computed
      tomography (CECT). METHODS: Risk factors and costs were assessed in consecutive
      patients. eGFR was evaluated in all patients, considering a tenability of 12
      months. For the three-month tenability and the pre-selection strategy based on
      risk factors for kidney disease, we extrapolated data by assuming equal
      distribution of patient characteristics. RESULTS: We included 1001 patients, mean
      age 59.9 +/- 13.6 years. Strategy with eGFR in all patients: eGFR measurements
      specifically performed for CECT in 645/1001 (in 356 patients the eGFR was already
      known). The total cost including costs of an extra visit to the hospital (49
      patients) and absence from work (11 patients) were ? 6037.20. Considering a
      tenability of 3 months, eGFR had to be measured in 786 patients, 60 would have
      paid an extra visit and 14 would have been absent from work: total cost ?
      7443.54. Pre-selection strategy: 807 patients had risk factors, necessitating
      eGFR measurement and an extra visit would be paid by 61. Fourteen patients would
      have been absent from work: total cost ? 7585.16. Of the patients with an eGFR
      <60 ml/min/1.73 m(2), 94.8% were identified including all with an eGFR <45
      ml/min/1.73 m(2). CONCLUSION: Determining eGFR based on risk factors for kidney
      disease is not more cost-effective than eGFR testing in all patients if the eGFR
      is tenable for 12 months or for 3 months.

PMID- 24930463
TI  - Acute abdominal pain, painful left shoulder and near collapse.

PMID- 24930464
TI  - A woman with abdominal pain and swelling.

PMID- 24930465
TI  - A woman with asymmetrical facial swelling.

PMID- 24930466
TI  - Divergent paradigm shifts in national, European and American cardiovascular
      prevention guidelines.

PMID- 24930467
TI  - A skin lesion that catches the eye.
AB  - Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is rare and only
      represents 1% of all cutaneous T-cell lymphomas. To our knowledge, only 40 cases
      have been described. It often presents with generalised skin lesions,
      preferentially affecting the extremities. There is a well-documented association
      with haemophagocytic syndrome. Treatment is difficult since PCGD-TCL is often
      resistant to chemotherapy and radiotherapy. Most case reports describe an
      aggressive clinical course with an estimated mean survival of 15 months. We
      present a 72-year-old female patient with stage IV primary cutaneous gamma-delta
      T-cell lymphoma. Our patient presented with fever, night sweats and multiple skin
      lesions (figure 1). Computed axial tomography of chest and abdomen revealed
      multiple solid nodular lesions in both kidneys. During admission a
      subconjunctival lesion appeared and progressed rapidly (figure 2).
      Histopathological examination of skin biopsy revealed infiltration of atypical
      lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of
      skin biopsy was compatible with PCGD-TLC. Clonal gamma-delta T-cells were also
      detected by immunohistochemical analysis of peripheral blood and bone marrow.
      Polymerase chain reaction amplification revealed clonal rearrangement of the T
      cell receptor gamma chain gene. These findings together were consistent with
      stage IV primary cutaneous gamma-delta T-cell lymphoma. The rapid progression of
      the subconjunctival extra-nodal manifestation is characteristic for the
      aggressive course of this lymphoma. Our patient was treated with two cycles of
      CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). However, her
      clinical condition deteriorated rapidly. She declined further therapy and died
      within three months of initial presentation. 

PMID- 24930469
TI  - Conversation with Jonathan Chick.
AB  - In this occasional series, we record the views and personal experiences of people
      who have especially contributed to the evolution of ideas in the journal's field
      of interest. Professor Jonathan Chick is now retired from a long and successful
      career as a clinician in addiction psychiatry for the National Health Service
      (NHS) in Scotland. He was formerly consultant psychiatrist at the Royal Edinburgh
      Hospital and senior lecturer at Edinburgh University. His career as an academic
      and as a renowned clinician in the field of alcohol dependence continues, with
      his most recent appointments being as a Professor at Queen Margaret's University
      in Edinburgh and as a Medical Director at Castle Craig Hospital. He is an author
      and editor of many books and articles concerning the prevention and treatment of
      alcohol problems. Professor Chick is also editor of Alcohol and Alcoholism.

PMID- 24930468
TI  - Motion capture and associated novel measurement devices for movement function in
      humans and animal models.

PMID- 24930470
TI  - Pyrroloquinoline quinone-secreting probiotic Escherichia coli Nissle 1917
      ameliorates ethanol-induced oxidative damage and hyperlipidemia in rats.
AB  - BACKGROUND: Chronic ethanol (EtOH) consumption is associated with oxidative
      tissue damage, decrease in antioxidant enzyme activities, and increase in hepatic
      and plasma lipids. This study investigates the effect of modified probiotic
      Escherichia coli Nissle 1917 (EcN) secreting pyrroloquinoline quinone (PQQ)
      against EtOH-induced metabolic disorder in rats. METHODS: Male Charles Foster
      rats were gavaged with EtOH (5 g/kg body weight [acute study] and 3 g/kg body
      weight per day for 10 weeks [chronic study]). RESULTS: Pretreatment of PQQ,
      vitamin C, and PQQ-secreting EcN prevented acute EtOH-induced oxidative damage in
      rats reflected by reduced lipid peroxidation in blood and liver and increased
      hepatic reduced glutathione. However, PQQ given externally was found to be most
      effective against acute EtOH toxicity. In the chronic study, rats treated with
      PQQ-secreting EcN showed remarkable reduction in oxidative tissue damage (liver,
      colon, blood, and kidney) with significant increase in antioxidant enzyme
      activities as compared to only EtOH-treated rats. Additionally, these rats had
      significantly lowered hepatic and plasma lipid levels with concomitant reduction
      in mRNA expression of fatty acid synthase (0.5-fold) and increase in mRNA
      expression of acyl coenzyme A oxidase (2.4-fold) in hepatic tissue. Antioxidant
      and hyperlipidemic effects of PQQ-secreting EcN are correlated with increased
      colonic short chain fatty acids (SCFAs; i.e., acetate, propionate, and butyrate)
      levels, and PQQ concentration in fecal samples (2-fold) and liver (4-fold).
      Extracted PQQ and vitamin C were given once a week, but they did not exhibit any
      ameliorative effect against chronic EtOH toxicity. CONCLUSIONS: Accumulated PQQ
      in tissues prevents hepatic and systemic oxidative damage. PQQ along with SCFAs
      reduced hyperlipidemia, which can be correlated with changes in mRNA expression
      of hepatic lipid metabolizing genes. Our study suggests that endogenous
      generation of PQQ by EcN could be an effective strategy in preventing alcoholic
      liver disease.

PMID- 24930471
TI  - A case-control study to identify predictors of 14-day mortality following
      carbapenem-resistant Acinetobacter baumannii bacteraemia.
AB  - Carbapenem-resistant Acinetobacter baumannii (CRAB) is an increasingly common
      nosocomial pathogen. We sought to identify clinical and microbiological
      predictors of 14-day mortality among patients with CRAB bacteraemia. This case
      control study included all adult patients in one Israeli hospital with CRAB on
      blood culture between July 2008 and June 2011. Cases were defined as patients who
      died within 14 days of bacteraemia onset and controls as patients who survived
      over 14 days. Sequence-typing of the blaOXA-51-like gene and REP-PCR identified
      CRAB clone groups. Logistic regression was performed to analyze predictors of 14
      day all-cause mortality. To correct for differences in treatment onset, Cox
      regression was used to examine the effect of receiving an active antibiotic.
      Eighty-three cases and 89 controls were included. Six major CRAB clone groups
      were identified, with 14-day mortality ranging from 17 to 66%. Independent
      predictors of 14-day mortality were severity of illness (OR = 1.38 for each 1
      point increase in Sequential Organ Failure Assessment (SOFA) score; 95% CI, 1.21,
      1.56), independence in activities of daily living (ADL) on admission (OR = 3.40;
      95% CI, 1.20, 9.67, for fully dependent vs. independent), surgery before
      bacteraemia (OR = 0.25; 95% CI, 0.11, 0.59) and clone group (OR = 7.76; 95% CI,
      2.52, 23.85, for the most virulent group vs. the reference group). In the
      multivariate Cox model using a propensity score to adjust for SOFA, clone, ADL
      and surgery, active antibiotic treatment was protective (HR = 0.30; 95% CI, 0.15,
      0.60). Differences in virulence between CRAB clones may partly explain
      heterogeneous results in previous studies of mortality following CRAB infection.

PMID- 24930472
TI  - Recreational screen-time among Chinese adolescents: a cross-sectional study.
AB  - BACKGROUND: Rapid urbanization in China has led to a proliferation of electronic
      entertainment media among youth. Prolonged screen time (ST; includes watching
      television and playing on computers, video game consoles, or mobile phones) is
      linked to poor health profiles. The aim of this study was to report recreational
      ST behaviors and ST correlates among Chinese adolescents living in two regions
      with different degrees of urbanization. METHODS: A cross-sectional, school-based
      survey (n = 3461 adolescents; aged 12-14 years old) living in inner-city Shanghai
      and a peri-urban region of Hangzhou. Students completed a questionnaire including
      family characteristics, daily ST, and information on family environment related
      to screen use. Recreational ST was categorized into two groups according to
      recommendations by the American Academy of Pediatrics (< or >=2 h/day). Parents
      reported their own ST and also reported educational attainment as a proxy for
      socioeconomic status. RESULTS: ST was higher among boys than girls and on
      weekends than weekdays. Peri-urban girls were more likely to exceed 2 h/day ST
      compared to inner-city girls on weekends. Having a father with no university
      degree, mother's TV viewing >=2 h/day, no ST rules at home, and eating meals in
      front of the TV were associated with higher ST on both weekdays and weekends, and
      regional differences were found for weekend ST. CONCLUSIONS: TV viewing and
      playing on the computer were the most prevalent ST behaviors among Chinese
      adolescents. Mobile phone playing was less prevalent but persistent throughout
      the week. More population-level surveillance and research is needed to monitor
      the trends in ST behaviors and to better understand the characteristics of those
      who are at risk.

PMID- 24930473
TI  - Bayesian nowcasting during the STEC O104:H4 outbreak in Germany, 2011.
AB  - A Bayesian approach to the prediction of occurred-but-not-yet-reported events is
      developed for application in real-time public health surveillance. The motivation
      was the prediction of the daily number of hospitalizations for the hemolytic
      uremic syndrome during the large May-July 2011 outbreak of Shiga toxin-producing
      Escherichia coli (STEC) O104:H4 in Germany. Our novel Bayesian approach addresses
      the count data nature of the problem using negative binomial sampling and shows
      that right-truncation of the reporting delay distribution under an assumption of
      time-homogeneity can be handled in a conjugate prior-posterior framework using
      the generalized Dirichlet distribution. Since, in retrospect, the true number of
      hospitalizations is available, proper scoring rules for count data are used to
      evaluate and compare the predictive quality of the procedures during the
      outbreak. The results show that it is important to take the count nature of the
      time series into account and that changes in the delay distribution occurred due
      to intervention measures. As a consequence, we extend the Bayesian analysis to a
      hierarchical model, which combines a discrete time survival regression model for
      the delay distribution with a penalized spline for the dynamics of the epidemic
      curve. Altogether, we conclude that in emerging and time-critical outbreaks,
      nowcasting approaches are a valuable tool to gain information about current
      trends. 

PMID- 24930474
TI  - Diabetic education in rural areas.
AB  - INTRODUCTION: Diabetes mellitus type II is a growing concern in the USA, with 6%
      of the population diagnosed with diabetes and another 5% having pre-diabetes. The
      prevalence of diabetes is 17% higher in rural areas than in central cities{1}.
      Adult diabetics living in rural areas often see negative outcomes related to
      their limited access to care, cultural barriers, and lack of educational
      resources. This article seeks to evaluate best evidence-based strategies directed
      at improving diabetic outcomes of rural populations through hemoglobin A1C
      (HbA1C) reductions. METHOD: A search of Medline, CIHNAL, PubMed, and Sage Pub was
      undertaken. The search was structured around the following key terms: adult,
      diabetes, education, hemoglobin a1c, and rural. The search limits were set to
      English-language publications between 2004 and 2012 in industrialized countries.
      Only articles from scholarly, peer-reviewed publications were considered.
      Literature that used an inpatient setting, focused on children or adolescents,
      and did not meet any inclusion criteria were excluded from this review. RESULTS:
      A total of 15 articles met the selection criteria from the 1819 citations sourced
      from the search. After reviewing the sources, nutritional patient education,
      motivational counseling and lifestyle modifications were found to be the most
      influential factors that favorably changed measurable outcomes for this
      population. Education for providers did not have an appreciable effect on patient
      outcomes. CONCLUSION: This review adds to the literature by outlining best
      practice guidelines for evidence-based practice based on current research.
      Primary care providers in rural areas should encourage their patients to actively
      participate in diabetes education when possible, and provide this education in a
      culturally competent manner.

PMID- 24930475
TI  - Optical correction of aphakia following unilateral infantile cataract removal.
AB  - PURPOSE: To compare primary intra-ocular lens (IOL) implantation with use of
      press-on spherical lens for aphakia correction following unilateral infantile
      cataract removal. METHODS: Sixty infants with a unilateral cataract underwent
      cataract surgery and were randomly assigned to the IOL (A group) or no IOL group
      (B group). Residual refractive error was corrected with spectacles in the A group
      and a press-on spherical lens was used to treat aphakia in the B group. Grating
      visual acuity (VA) was measured and patients were followed for up to 1 year.
      RESULTS: LogMAR VA in the operated eyes of both groups was significantly better 1
      year than 1 month after surgery. Mean logMAR VA difference between 1 year and 1
      month after surgery was higher in the A group (0.457 +/- 0.110) than in the B
      group (0.323 +/- 0.114, p < 0.0001). Serious inflammation occurred significantly
      more often in the A group than in the B group (p = 0.007). Visual axis opacity
      occurred more often in the A group than in the B group (pupillary membrane: A:
      six eyes, 20%, B: none, p = 0.024; lens reproliferation: A: 10 eyes, 33%, B: two
      eyes, 7%, p = 0.021). Glaucoma occurred equally in both groups (p = 0.612). No
      other complications occurred. CONCLUSIONS: Primary IOL implantation appears to be
      a relatively safe, effective optical correction strategy following unilateral
      cataract extraction in this age group. Patients for whom an IOL is not suitable
      can be treated with a press-on spherical lens for optical correction.

PMID- 24930476
TI  - Case of subepidermal bullous disease with diffuse esophageal involvement
      presenting with immunoglobulin G autoantibodies to both the BP180 NC16a and C
      terminal domains, and immunoglobulin A autoantibodies to the BP180 NC16a domain.

PMID- 24930477
TI  - Measurement of non-coumarin anticoagulants and their effects on tests of
      Haemostasis: Guidance from the British Committee for Standards in Haematology.

PMID- 24930478
TI  - Effectiveness and implementation of an obesity prevention intervention: the HeLP
      her Rural cluster randomised controlled trial.
AB  - BACKGROUND: To impact on the obesity epidemic, interventions that prevent weight
      gain across populations are urgently needed. However, even the most efficacious
      interventions will have little impact on obesity prevention unless they are
      successfully implemented in diverse populations and settings. Implementation
      research takes isolated efficacy studies into practice and policy and is
      particularly important in obesity prevention where there is an urgent need to
      accelerate the evidence to practice cycle. Despite the recognised need, few
      obesity prevention interventions have been implemented in real life settings and
      to our knowledge rarely target rural communities. METHODS: Here we describe the
      rationale, design and implementation of a Healthy Lifestyle Program for women
      living in small rural communities (HeLP-her Rural). The primary goal of HeLP-her
      Rural is to prevent weight gain using a low intensity, self-management
      intervention. Six hundred women from 42 small rural communities in Australia will
      be randomised as clusters (n-21 control towns and n = 21 intervention towns). A
      pragmatic randomised controlled trial methodology will test efficacy and a
      comprehensive mixed methods community evaluation and cost analysis will inform
      effectiveness and implementation of this novel prevention program. DISCUSSION:
      Implementing population interventions to prevent obesity is complex, costly and
      challenging. To address these barriers, evidence based interventions need to move
      beyond isolated efficacy trials and report outcomes related to effectiveness and
      implementation. Large pragmatic trials provide an opportunity to inform both
      effectiveness and implementation leading to potential for greater impact at the
      population level. Pragmatic trials should incorporate both effectiveness and
      implementation outcomes and a multidimensional methodology to inform scale-up to
      population level. The learnings from this trial will impact on the design and
      implementation of population obesity prevention strategies nationally and
      internationally. TRIAL REGISTRATION: ANZ clinical trial registry
      ACTRN12612000115831. Date of registration 24/01/2012.

PMID- 24930479
TI  - Control of proximal gastric bleeding through transgastric insertion of
      laparoscopic ports.

PMID- 24930480
TI  - Neutrophil gelatinase-associated lipocalin associated with irreversibility of pre
      liver transplant kidney dysfunction.
AB  - Kidney outcomes in early post-liver transplantation (LT) are crucial for long
      term prognosis, but difficult to predict. Among 203 adult LT patients, we studied
      the value of plasma neutrophil gelatinase-associated lipocalin (NGAL) measured
      pre-LT for predicting acute kidney injury (AKI), kidney-replacement therapy
      within three months, and kidney dysfunction at three months post-LT. Glomerular
      filtration rate (GFR) was estimated by creatinine-based and cystatin C-based
      equations. Highest NGAL levels were among patients on pre-LT kidney-replacement
      therapy, whereas NGAL exceeded 200 MUg/L in only three (2%) patients with pre-LT
      GFR >60 mL/min. Pre-LT NGAL >260 MUg/L predicted GFR <60 mL/min at three months
      post-LT (OR 17.8, 95% CI 2.1-153) independently of 19 other variables reflecting
      recipient characteristics, liver and kidney function, perioperative hemodynamic
      stress, and immunosuppression. Of 81 patients with pre-LT GFR <60 mL/min, 48% had
      GFR <60 mL/min at three months, and an NGAL level >260 MUg/L predicted this
      outcome with 90% specificity and 46% sensitivity. NGAL failed to predict post-LT
      AKI or need for temporary kidney-replacement therapy. In conclusion, NGAL
      independently predicted irreversibility of pre-LT kidney dysfunction and could
      thus help in optimizing patient care and in the decision to perform combined
      liver-kidney transplantation. Pre-LT NGAL was not useful in patients with
      preserved pre-LT kidney function or in predicting post-LT AKI.

PMID- 24930482
TI  - Immune cell function assay does not identify biopsy-proven pediatric renal
      allograft rejection or infection.
AB  - Management of pediatric renal transplant patients involves multifactorial
      monitoring modalities to ensure allograft survival and prevent opportunistic
      infection secondary to immunosuppression. An ICFA, which utilizes CD4 T-cell
      production of ATP to assess immune system status, has been used to monitor
      transplant recipients and predict susceptibility of patients to rejection or
      infection. However, the validity of this assay to reflect immune status remains
      unanswered. In a two-yr retrospective study that included 31 pediatric renal
      transplant recipients, 42 patient blood samples were analyzed for immune cell
      function levels, creatinine, WBC (white blood cell) count, immunosuppressive drug
      levels, and viremia, concurrent with renal biopsy. T-cell ATP production as
      assessed by ICFA levels did not correlate with allograft rejection or with the
      presence or absence of viremia. ICFA levels did not correlate with serum
      creatinine or immunosuppressive drug levels, but did correlate with WBC count.
      The ICFA is unreliable in its ability to reflect immune system status in
      pediatric renal transplantation. Further investigation is necessary to develop
      methods that will accurately predict susceptibility of pediatric renal transplant
      recipients to allograft rejection and infection. 

PMID- 24930481
TI  - Husbandry factors and the resumption of luteal activity in open and zero-grazed
      dairy cows in urban and peri-urban kampala, Uganda.
AB  - The study investigated the influence of selected husbandry factors on interval to
      resumption of post-partum cyclicity among dairy cows in urban and peri-urban
      Kampala. A prospective study of 85 day post-partum period of 59 dairy cows in
      open (n = 38) and zero grazing (n = 21) systems was conducted on 24 farms. Cows
      of parity 1-6 were recruited starting 15-30 days post-partum. Progesterone (P4)
      content in milk taken at 10-12 day intervals was analysed using ELISA. The cow P4
      profiles were classified into 'normal' (< 56 days), 'delayed' (> 56 days),
      'ceased' or 'prolonged' (if started < 56 days but with abnormal P4 displays)
      resumption of luteal activity and tested for association with husbandry and cow
      factors. Of the 59 cows, luteal activity in 81.4% resumed normally and in 18.6%,
      delayed. Only 23.7% maintained regular luteal activity, while the others had
      ceased (10.2%), prolonged (37.3%) or unclear luteal activity (20.3%). There were
      no differences between open and zero-grazed cows. Milk production was higher (p <
      0.05) in zero than open grazing, in urban than peri-urban and in cows fed on brew
      waste (p < 0.001) compared with mill products and banana peels. Results suggest
      that luteal activity resumes normally in a majority of cows, although only a
      minority experienced continued normal cyclicity once ovulation had occurred, in
      the two farming systems irrespective of feed supplements or water, and that
      supplementing with brew waste is beneficial for milk production.

PMID- 24930483
TI  - Periocular sebaceous gland carcinoma: do androgen receptor (NR3C4) and nuclear
      survivin (BIRC5) have a prognostic significance?
AB  - PURPOSE: The study aimed at evaluating the expression of androgen receptor (AR)
      and nuclear survivin (NS) in periocular sebaceous gland carcinoma (SGC) and to
      determine whether this expression is associated with histopathological features,
      markers of apoptosis and proliferation and with clinical outcomes. METHODS: This
      was a retrospective, comparative case series which included 56 patients with a
      biopsy-proven periocular SGC. Immunohistochemical staining for AR, survivin, p53
      and Ki-67 was analysed in all cases. RESULTS: All patients expressed AR, p53 and
      Ki-67 in the nucleus of tumour cells. Twenty-four patients (42.8%) had a high AR
      score, and 32 patients (57.2%) had a low AR score. Twenty-four (42.8%) patients
      expressed survivin in the nucleus of tumour cells. Nine (37.5%) had a high NS
      score, and 15 (62.5%) had a low NS score. Patients with a high AR score had a
      greater recurrence (p < 0.005), higher expression of Ki-67 (p < 0.0001) and a
      lower p53 expression (p < 0.005). Nuclear expression of survivin correlated with
      a high Ki-67 labelling index (0.0001) and low p53 expression (<0.005). Neither
      nuclear expression of survivin nor the NS score correlated with any
      clinicopathological features. CONCLUSION: Expression of AR significantly impacts
      prognosis and is thus promising prognostic marker in periocular SGC.

PMID- 24930484
TI  - Liver stiffness-based model for prediction of hepatocellular carcinoma in chronic
      hepatitis B virus infection: comparison with histological fibrosis.
AB  - BACKGROUND & AIMS: Liver stiffness (LS) value using transient elastography is a
      reliable, non-invasive tool for assessing liver fibrosis. LS-based prediction
      model, LSPS (=LS value * spleen diameter/platelet count) is well correlated with
      the risk of developing portal hypertension-related cirrhotic complications. Here,
      we assessed the prognostic performance of LSPS in predicting the development of
      hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).
      METHODS: Between 2006 and 2010, we recruited 227 patients with CHB who underwent
      liver biopsy and LS measurement. The major end point was HCC development.
      RESULTS: Median age was 45 years and 156 (68.7%) patients were male. During the
      follow-up period (median, 61 months), HCC developed in 18 patients. Patient with
      HCC had a higher LS value, a longer spleen, and lower platelet counts (all P <
      0.05) than those without HCC. On multivariate analysis, LSPS was identified as an
      independent predictor of HCC development [hazard ratio (HR) 1.541, P < 0.001]
      after adjusting for age, serum albumin level and histological fibrosis stage.
      When patients were stratified into three groups (LSPS <1.1, 1.1-2.5 and >2.5),
      the 5-year cumulative risk of HCC increased significantly in association with a
      higher LSPS value (4.0, 13.8, 36.2%, respectively, P < 0.001). Patients with LSPS
      1.1-2.5 (HR 2.0, P = 0.032) and LSPS > 2.5 (HR 8.7, P = 0.002) had a higher risk
      of developing HCC than those with LSPS < 1.1. CONCLUSIONS: LS value-spleen
      diameter to platelet ratio score is useful for assessing the risk of HCC
      development and careful surveillance strategies are required in an individual
      manner.

PMID- 24930485
TI  - Deaggregators inhibit TNF-alpha-induced leukocyte adhesion in vitro by breaking
      up hydrophobic lipophilic interactions.
AB  - AIM: Deaggregators (deAgrs) are nontoxic organic molecules that possess the
      ability to deaggregate simple aggregates formed by hydrophobic lipophilic
      interactions (HLI). Since HLI-driven organic molecule aggregates may induce
      leukocyte adhesion, we investigated the influence of deAgrs on TNF-alpha-mediated
      leukocyte adhesion in vitro. METHODS: For adhesion studies, vascular endothelial
      cells or smooth muscle cells monolayers were treated with TNF-alpha (10 MUg/L)
      and deAgrs for 24 h, followed by addition of monocytes or neutrophils suspension.
      The non-adherent leukocytes were rinsed, and the number of attached leukocytes
      was measured using an ELISA plate reader. Simultaneously, fluorescence probes Np
      12 and Np-Ch were used to measure the deaggregating efficiencies of these deAgrs.
      RESULTS: Among the nine deAgrs tested,eight significantly reduced the cell
      adhesion rates with the order of efficiencies: 260 > 160 > 568 > ZPMOP > R68 >
      640 > TB6PMOP > CNS, but TBHQ had no effect. The deAgrs for deaggregating an
      aggregated probe (Np-12 or Np-Ch) exhibited a similar order of efficiencies: 260
      > 160 > 568 > ZPMOP > R68 > 640 > TB6PMOP > CNS > 12-AA > 11-AA > TBHQ. Spearman
      correlation coefficient analyses indicated that the adherent rates of leukocytes
      to endothelial cells or smooth muscle cells treated with deAgrs had significantly
      negative correlation to their deaggregating abilities. CONCLUSION: DeAgrs
      effectively inhibit TNF-alpha-mediated leukocyte adhesion in vitro by breaking up
      hydrophobic lipophilic interactions, thus may be further tested for blocking
      atherogenesis.

PMID- 24930486
TI  - A cell-based, high-throughput homogeneous time-resolved fluorescence assay for
      the screening of potential kappa-opioid receptor agonists.
AB  - AIM: The aim of this study was to identify kappa-opioid receptor (KOR) agonists
      from a library of 80 000 small-molecule compounds and provide the experimental
      basis for the development of new analgesic candidates. METHODS: The cell-based,
      high-throughput screen for human KOR agonists was based on the LANCE cAMP assay.
      Preliminary structure-activity relationship (SAR) analysis was applied according
      to the compounds' structures. An acetic acid twisting experiment was used to
      verify the pharmacodynamics. RESULTS: In total, 31 compounds were identified as
      KOR agonists after preliminary and secondary screening. Of these compounds, five
      demonstrated significant KOR-stimulating activity that was comparable to U
      50,488, a selective KOR agonist. The EC50 values for I-7, I-8, I-10, II-5, and II
      8 were 13.34 +/- 1.65, 14.01 +/- 1.84, 9.57 +/- 0.19, 14.94 +/- 0.64, and 8.74 +/
      0.72 nmol/L, respectively. Based on SAR studies, the stimulating activity of
      compounds with 5-phenyl-7-(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo [1, 5-a]
      pyrimidine (group I) and 3,4-dimethoxy-N-(2-oxoethyl)-N-p-tolylbenzenesulfonamide
      (group II) parent structures were higher than the compound with a 5-hydroxy-2
      methylbenzofuran-3-carboxylic acid (group III) parent structure. Pharmacodynamic
      experiments indicated that 20-40 MUg/kg ip of compounds I-10 and II-8
      significantly decreased the number of writhes induced by acetic acid; this
      finding is consistent with the SAR studies. Furthermore, the analgesic effects of
      compounds I-10 and II-8 were significantly antagonized in the presence of the
      selective KOR antagonist nor-BNI. CONCLUSION: These findings collectively
      indicate that compounds I-10 and II-8 exhibit significant analgesic activities,
      providing evidence, at least in part, for their clinical application as new
      analgesic drugs.

PMID- 24930487
TI  - Photosynthetic, hydraulic and biomass properties in closely related C3 and C4
      species.
AB  - In plants, most water is absorbed by roots and transported through vascular
      conduits of xylem which evaporate from leaves during photosynthesis. As
      photosynthesis and transport processes are interconnected, it was hypothesized
      that any variation in water transport demand influencing water use efficiency
      (WUE), such as the evolution of C4 photosynthesis, should affect xylem structure
      and function. Several studies have provided evidence for this hypothesis, but
      none has comprehensively compared photosynthetic, hydraulic and biomass
      allocation properties between C3 and C4 species. In this study, photosynthetic,
      hydraulic and biomass properties in a closely related C3 Tarenaya hassleriana and
      a C4 Cleome gynandra are compared. Light response curves, measured at 30 degrees
      C, showed that the C4 C. gynandra had almost twice greater net assimilation rates
      than the C3 T. hassleriana under each increasing irradiation level. On the
      contrary, transpiration rates and stomatal conductance were around twice as high
      in the C3 , leading to approximately 3.5 times higher WUE in the C4 compared with
      the C3 species. The C3 showed about 3.3 times higher hydraulic conductivity, 4.3
      times greater specific conductivity and 2.6 times higher leaf-specific
      conductivity than the C4 species. The C3 produced more vessels per xylem area and
      larger vessels. All of these differences resulted in different biomass
      properties, where the C4 produced more biomass in general and had less root to
      shoot ratio than the C3 species. These results are in support of our previous
      findings that WUE, and any changes that affect WUE, contribute to xylem evolution
      in plants.

PMID- 24930488
TI  - Is blood-flow-restricted low-load resistance exercise really stress free?

PMID- 24930489
TI  - Establishing and managing a periodontal biobank for research: the sharing of
      experience.
AB  - Periodontal bio-repositories, which allow banking of clinically validated human
      data and biological samples, provide an opportunity to derive biomarkers for
      periodontal diagnosis, prognosis and therapeutic activities which are expected to
      improve patient management. This article presents the establishing of the
      Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in
      2011 with the aim to facilitate periodontal research. Partnerships were
      established with collaborating centres. Policies on specimen access, authorship
      and acknowledgement policies were agreed upon by all participating centres before
      the initiation of the periodontal biobank. Ethical approval for the collection of
      samples and data were obtained from institutional ethics review boards. A broad
      based approach for informed consent was used, which covered areas related to
      quality of life impacts, genetics and molecular aspects of periodontal disease.
      Sample collection and processing was performed using a standardized protocol.
      Biobanking resources such as equipment and freezers were shared with the
      Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the
      development of the MPDBS, challenges that were previously faced by the MOCDTBS
      were considered. Future challenges in terms of ethical and legal issues will be
      faced when international collaborations necessitate the transportation of
      specimens across borders. 

PMID- 24930490
TI  - Proximal attrition facets: morphometric, demographic, and aging characteristics.
AB  - Although interproximal attrition is considered to be limited in modern
      populations, it has important clinical implications. However, in contrast to
      occlusal attrition, proximal attrition receives limited scientific attention. The
      main purpose of the current study was to fill this void. Seven-hundred and sixty
      five teeth were collected from 255 skulls of subjects 18-75 yr of age. For each
      individual, three mandibular teeth (the first and second premolars and the first
      molar) were examined for proximal attrition facets (PAFs). The results provide
      detailed information on the size, shape, and location of the facets according to
      age cohort, gender, and ethnicity. The validity of the method used to measure the
      facets was also examined. The major findings were as follows: PAFs are usually
      located on the upper half of the crown proximal aspect; in each tooth, the mesial
      facet is more lingually positioned and the distal facet is more buccally
      positioned; the majority of the facets are subrectangular in shape; the size of
      the facets tends to increase in an anteroposterior direction (from premolars to
      molars); and facet size and location are age- and sex-dependent and ethnicity
      independent. It is our recommendation that dentists bear in mind that
      interproximal attrition is a dynamic, long-term process and needs to be
      considered in many clinical scenarios.

PMID- 24930491
TI  - Skin temperature during sunbathing--relevance for skin cancer.
AB  - It has been found that exposure to heat and infrared radiation (IR) can be
      carcinogenic, and that a combination of ultraviolet radiation (UVR) and IR
      possibly amplifies carcinogenesis. To investigate how the skin temperature is
      affected by sunbathing, we measured the skin temperature on 20 healthy volunteers
      over 6 days' sun holiday in Egypt. Temperatures were measured with an infrared
      thermometer gun at 8 skin sites on the volunteers while they were indoors in the
      morning and when sunbathing during the day. Skin temperatures were higher during
      sunbathing (33.5  degrees C +/- 2.1  degrees C) (mean +/- SD) than when indoors
      in the morning (32.6  degrees C +/- 1.4  degrees C) (mean +/- SD) (P < 0.0001).
      The average skin temperature for men was higher than for women by 0.40  degrees C
      in the morning (P = 0.02) and by 0.44  degrees C during sunbathing (P < 0.0001).
      Our results show that sunbathing has an impact on skin temperature, which
      possibly by activation of the heat shock response, is likely to contribute to the
      immediate and delayed effects of UV in a way that has to be found out in future
      studies. 

PMID- 24930492
TI  - Association between periodontitis and preeclampsia in never-smokers: a
      prospective study.
AB  - AIM: The aim of this prospective study was to investigate the relationship
      between periodontitis and preeclampsia in never-smokers. MATERIALS AND METHODS:
      Pregnant women were recruited at 21 to 24 weeks of gestation from March 2009 to
      June 2013. Information on demographics, health behaviours, obstetric history, and
      systemic diseases that can influence periodontal status and preeclampsia was
      collected. Full-mouth periodontal probing was performed by two trained examiners.
      The inter-examiner Kappa value was 0.822 for clinical attachment loss (CAL).
      Periodontitis was defined as clinical periodontal attachment loss (CAL) of 4.0 mm
      or greater on 2 or more sites not on the same tooth. Information on the
      occurrence of preeclampsia was collected by five obstetricians. RESULTS: We
      studied a total of 283 subjects, comprised of 67 subjects with periodontitis and
      216 subjects without periodontitis. Of these, 13 (4.6%) women were diagnosed with
      preeclampsia. After adjusting for all confounders, the adjusted odds ratio of
      periodontitis for preeclampsia was 5.56 (95% confidence interval of 1.49-20.71).
      CONCLUSIONS: There was a significant relationship between periodontitis and the
      occurrence of preeclampsia among never-smokers.

PMID- 24930493
TI  - The air-sea interface and surface stress under tropical cyclones.
AB  - Tropical cyclone track prediction is steadily improving, while storm intensity
      prediction has seen little progress in the last quarter century. Important
      physics are not yet well understood and implemented in tropical cyclone forecast
      models. Missing and unresolved physics, especially at the air-sea interface, are
      among the factors limiting storm predictions. In a laboratory experiment and
      coordinated numerical simulation, conducted in this work, the microstructure of
      the air-water interface under hurricane force wind resembled Kelvin-Helmholtz
      shear instability between fluids with a large density difference. Supported by
      these observations, we bring forth the concept that the resulting two-phase
      environment suppresses short gravity-capillary waves and alters the aerodynamic
      properties of the sea surface. The unified wave-form and two-phase
      parameterization model shows the well-known increase of the drag coefficient (Cd)
      with wind speed, up to ~30 ms(-1). Around 60 ms(-1), the new parameterization
      predicts a local peak of Ck/Cd, under constant enthalpy exchange coefficient Ck.
      This peak may explain rapid intensification of some storms to major tropical
      cyclones and the previously reported local peak of lifetime maximum intensity
      (bimodal distribution) in the best-track records. The bimodal distribution of
      maximum lifetime intensity, however, can also be explained by environmental
      parameters of tropical cyclones alone.

PMID- 24930494
TI  - Strategies to address management challenges in larger intensive care units.
AB  - AIM: To illustrate the need for and suggest strategies that will enhance
      sustainable management of a large intensive care unit (ICU). BACKGROUND: The
      challenges faced by intensive care nursing in South Africa are well documented.
      However, there appear to be no strategies available to assist nurses to manage
      large ICUs or for ICU managers to deal with problems as they arise. METHODS: Data
      sources to illustrate the need for strategies were challenges described by ICU
      managers in the management of large ICUs. A purposive sample of managers was
      included in individual interviews during compilation of evidence regarding the
      challenges experienced in the management of large ICUs. The challenges were
      presented at the Critical Care Society of Southern Africa Congress held on 28
      August to 2 September 2012 in Sun City North-West province, South Africa.
      RESULTS: Five strategies are suggested for the challenges identified: divide the
      units into sections; develop a highly skilled and effective nursing workforce to
      ensure delivery of quality nursing care; create a culture to retain an effective
      ICU nursing team; manage assets; and determine the needs of ICU nurses.
      CONCLUSION: ICUs need measures to drive the desired strategies into actions to
      continuously improve the management of the unit. Future research should be aimed
      at investigating the effectiveness of the strategies identified. IMPLICATIONS FOR
      NURSING MANAGEMENT: This research highlights issues relating to large ICUs and
      the strategies will assist ICU managers to deal with problems related to large
      unit sizes, shortage of trained ICU nurses, use of agency nurses, shortage of
      equipment and supplies and stressors in the ICU. The article will make a
      contribution to the body of nursing literature on management of ICUs.

PMID- 24930495
TI  - Age-job satisfaction relationship for Japanese public school teachers: a
      comparison of teachers' labor union members and professional and technical
      employee members of private company labor unions.
AB  - OBJECTIVES: This study investigated the characteristics of the age-job
      satisfaction relationship for public school teachers. Past studies examining this
      relationship have found both linear and non-linear relationships. However, such
      studies have yet to examine these relationships by comparing job satisfaction of
      teachers with that of company employees in the same cultural context. In order to
      investigate the characteristics of Japanese teachers' working environment, we
      examined how different the age-job satisfaction relationships were between
      teachers and company employees. METHODS: We conducted hierarchical polynomial
      regression analyses with four job satisfaction variables to compare the age-job
      satisfaction relationships of Japanese public elementary, junior and high school
      teachers with Japanese professional and technical workers who belonged to their
      respective labor unions. RESULTS: 1) Among teachers, the effects of age on
      overall job satisfaction and satisfaction with pay were significantly negative,
      and the effects of age on satisfaction with human relationships and working hours
      were not significant. 2) Among company employees, these four kinds of
      satisfactions had U shaped relationships with age. 3) Compared to company
      employees, teachers showed higher intrinsic satisfaction and lower extrinsic
      satisfaction. CONCLUSIONS: The age-job satisfaction relationship for teachers
      decreases with age. This result may be explained by the excessive workload of
      Japanese teachers, a characteristic of their working environment. Elderly
      teachers' burnout may be related to this characteristic. It may be necessary for
      elderly teachers to be supported in order to enhance their job satisfaction,
      especially extrinsic satisfaction.

PMID- 24930496
TI  - How a protein can remain stable in a solvent with high content of urea: insights
      from molecular dynamics simulation of Candida antarctica lipase B in urea :
      choline chloride deep eutectic solvent.
AB  - Deep eutectic solvents (DESs) are utilized as green and inexpensive alternatives
      to classical ionic liquids. It has been known that some of DESs can be used as
      solvent in the enzymatic reactions to obtain very green chemical processes. DESs
      are quite poorly understood at the molecular level. Moreover, we do not know much
      about the enzyme microstructure in such systems. For example, how some hydrolase
      can remain active and stable in a deep eutectic solvent including 9 M of urea? In
      this study, the molecular dynamics of DESs as a liquid was simulated at the
      molecular level. Urea : choline chloride as a well-known eutectic mixture was
      chosen as a model DES. The behavior of the lipase as a biocatalyst was studied in
      this system. For comparison, the enzyme structure was also simulated in 8M urea.
      The thermal stability of the enzyme was also evaluated in DESs, water, and 8M
      urea. The enzyme showed very good conformational stability in the urea : choline
      chloride mixture with about 66% urea (9 M) even at high temperatures. The results
      are in good agreement with recent experimental observations. In contrast,
      complete enzyme denaturation occurred in 8M urea with only 12% urea in water. It
      was found that urea molecules denature the enzyme by interrupting the intra-chain
      hydrogen bonds in a "direct denaturation mechanism". However, in a urea : choline
      chloride deep eutectic solvent, as a result of hydrogen bonding with choline and
      chloride ions, urea molecules have a low diffusion coefficient and cannot reach
      the protein domains. Interestingly, urea, choline, and chloride ions form
      hydrogen bonds with the surface residues of the enzyme which, instead of lipase
      denaturation, leads to greater enzyme stability. To the best of our knowledge,
      this is the first study in which the microstructural properties of a
      macromolecule are examined in a deep eutectic solvent. 

PMID- 24930497
TI  - Synthesis of rare earth doped yttrium-vanadate nanoparticles encapsulated within
      apoferritin.
AB  - Luminescent europium (Eu) and dysprosium (Dy) doped yttrium-vanadate (Y-V)
      nanoparticles (NPs) were synthesized in the cavity of the protein, apoferritin. Y
      V NPs were synthesized by incubating a solution of apoferritin with Y(3+) and
      VO3(-) ions in the presence of ethylene diamine-N-N'-diacetic acid (EDDA). EDDA
      plays an important role in preventing Y-vanadate precipitation in bulk solution
      by chelating the Y(3+) ions. Using high resolution electron microscopy, the
      obtained NPs in the apoferritin cavities were confirmed to be amorphous, and to
      consist of Y and V. Eu-doped Y-V (Y-V:Eu) NPs were synthesized by the same
      procedure as Y-V NPs, except that Eu(NO3)3 was added. Y-V:Eu NPs exhibited a
      strong absorption peak due to the O-V charge transfer transition and remarkable
      luminescence at 618 nm due to the (5)D0 -> (7)F2 transition. The luminescence
      lifetime of Y:Eu and Y-V:Eu NPs measured in H2O and D2O solution showed reduction
      of non-radiative transition to the O-H vibration in Y-V:Eu NPs. Accordingly, Y-V
      NPs showed strong luminescence compared to Y:Eu NPs. Dy-doped Y-V NPs were also
      synthesized in apoferritin cavities and showed luminescence peaks at 482 nm and
      572 nm, corresponding to (4)F9/2 -> (6)H15/2 and (4)F9/2 -> (6)H13/2 transitions.
      These NPs stably dispersed in water solution since their aggregation was
      prevented by the protein shell. NPs encapsulated in the protein are likely to be
      biocompatible and would have significant potential for biological imaging
      applications. 

PMID- 24930498
TI  - The effect of age on the systemic inflammatory response in patients with
      community-acquired pneumonia.
AB  - Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality
      worldwide. Increasing age has been associated with elevated circulating levels of
      pro-inflammatory mediators. We aimed to determine the impact of ageing on the
      systemic inflammatory response to CAP. In total 201 CAP patients were enrolled.
      Blood samples were obtained upon presentation, and on days 2, 3 and 5. For the
      current analysis patients<=50 and >=80 years were included. The Pneumonia
      Severity Index (PSI) score was calculated at presentation. The study encompassed
      46 CAP patients aged <=50 years (median 37 years) and 41 CAP patients aged >=80
      years (median 84 years). In both groups Streptococcus pneumoniae was the common
      causative microorganism. Whereas most young patients had a PSI score of I (54%),
      98% of elderly patients had a PSI score>=III (p<0.001). Four elderly patients
      died vs. none of the young patients (p 0.045). Older patients demonstrated lower
      serum C-reactive protein levels on admission and during the course of their
      hospitalization (p 0.001) in spite of more severe disease. Serum concentrations
      of pro-inflammatory (interleukin (IL)-6 and IL-8) and anti-inflammatory cytokines
      (IL-10 and IL-1 receptor antagonist) did not differ between age groups, although
      admission IL-8 levels tended to be higher in elderly patients (p 0.05). Cytokine
      levels were positively correlated with PSI in young but not in elderly patients.
      These results suggest that elderly patients show an absolute (C-reactive protein)
      or relative (cytokines) reduction in their systemic inflammatory response on
      admission for CAP.

PMID- 24930500
TI  - Quiet please! Drug round tabards: are they effective and accepted? A mixed method
      study.
AB  - BACKGROUND: The use of drug round tabards is a widespread intervention that is
      implemented to reduce the number of interruptions and medication administration
      errors (MAEs) by nurses; however, evidence for their effectiveness is scarce.
      PURPOSE: Evaluation of the effect of drug round tabards on the frequency and type
      of interruptions, MAEs, the linearity between interruptions and MAEs, as well as
      to explore nurses' experiences with the tabards. STUDY DESIGN: A mixed methods
      before-after study, with three observation periods on three wards of a Dutch
      university hospital, combined with personal inquiry and a focus group with
      nurses. METHODS: In one pre-implementation period and two post-implementation
      periods at 2 weeks and 4 months, interruptions and MAEs were observed during drug
      rounds. Descriptive statistics and univariable linear regression were used to
      determine the effects of the tabard, combined with personal inquiry and a focus
      group to find out experiences with the tabard. FINDINGS: A total of 313
      medication administrations were observed. Significant reductions in both
      interruptions and MAEs were found after implementation of the tabards. In the
      third period, a decrease of 75% in interruptions and 66% in MAEs was found.
      Linear regression analysis revealed a model R2 of 10.4%. The implementation
      topics that emerged can be classified into three themes: personal considerations,
      patient perceptions, and considerations regarding tabard effectiveness.
      CONCLUSIONS: Our study indicates that this intervention contributes to a
      reduction in interruptions and MAEs. However, the reduction in MAEs cannot be
      fully explained by the decrease in interruptions alone; other factors may have
      also influenced the effect on MAEs. We advocate for further research on
      complementary interventions that contribute to a further reduction of MAEs.
      CLINICAL RELEVANCE: We can conclude that drug round tabards are effective to
      improve medication safety and are therefore important for the quality of nursing
      care and the reduction of MAEs.

PMID- 24930501
TI  - Carotenoid retention of biofortified provitamin A maize (Zea mays L.) after
      Zambian traditional methods of milling, cooking and storage.
AB  - Provitamin A biofortified maize hybrids were developed to target vitamin A
      deficient populations in Africa. The purpose of this study was to evaluate the
      degradation of carotenoids after milling, cooking, and storage among biofortified
      varieties released in Zambia. The biofortified maize hybrids contained 7.5 to
      10.3 MUg/g dry weight (DW) of provitamin A as measured by beta-carotene
      equivalents (BCE). There was virtually no degradation due to milling. The BCE
      retention was also high (>100%) for most genotypes when the maize was cooked into
      thick (nshima) and thin porridge, but showed a lower BCE retention (53-98%) when
      cooked into samp (dehulled kernels). Most of the degradation occurred in the
      first 15 days of storage of the maize as kernels and ears (BCE retention 52-56%)
      which then stabilized, remaining between 30% and 33% of BCE after six months of
      storage. In conclusion, most of the provitamin A degradation in biofortified
      maize hybrids occurred during storage compared with cooking and the magnitude of
      this effect varied among genotypes. 

PMID- 24930499
TI  - Up-regulation of neogenin-1 increases cell proliferation and motility in gastric
      cancer.
AB  - Although elevated expression of neogenin-1 has been detected in human gastric
      cancer tissue, its role in gastric tumorigenesis remains unclear due to the lack
      of neogenin-1 studies in cancer. Therefore, we demonstrated here the function and
      regulatory mechanism of neogenin-1 in gastric cancer. Neogenin-1 ablation
      decreased proliferation and migration of gastric cancer cells, whereas its over
      expression reversed these effects. Xenografted analyses using gastric cancer
      cells displayed statistically significant inhibition of tumor growth by neogenin
      1 depletion. Interestingly, galectin-3 interacted with HSF-1 directly, which
      facilitated nuclear-localization and binding on neogenin-1 promoter to drive its
      transcription and gastric cancer cell motility. The galectin-3-increased gastric
      cancer cell motility was down-regulated by HSF-1 depletion. Moreover, the
      parallel expression patterns of galectin-3 and neogenin-1, as well as those of
      HSF-1 and neogenin-1, were detected in the malignant tissues of gastric cancer
      patients. Taken together, high-expression of neogenin-1 promotes gastric cancer
      proliferation and motility and its expression is regulated by HSF-1 and galectin
      3 interaction. In addition, we propose further studies for neogenin-1 and its
      associated pathways to provide them as a proper target for gastric cancer
      therapy. 

PMID- 24930503
TI  - Thermoelectric voltage measurements of atomic and molecular wires using
      microheater-embedded mechanically-controllable break junctions.
AB  - We developed a method for simultaneous measurements of conductance and
      thermopower of atomic and molecular junctions by using a microheater-embedded
      mechanically-controllable break junction. We find linear increase in the
      thermoelectric voltage of Au atomic junctions with the voltage added to the
      heater. We also detect thermopower oscillations at several conductance quanta
      reflecting the quantum confinement effects in the atomic wire. Under high heater
      voltage conditions, on the other hand, we observed a peculiar behaviour in the
      conductance dependent thermopower, which was ascribed to a disordered contact
      structure under elevated temperatures. 

PMID- 24930502
TI  - Comprehensive evaluation of cardiac function and detection of myocardial
      infarction based on a semi-automated analysis using full-volume real time three
      dimensional echocardiography.
AB  - OBJECTIVE: Quantitative left ventricular mass (LVM) as well as regional strain
      values may be obtained from full-volume real time 3D echocardiography data via
      semi-automated feature tracking and represent indices of heart function, both in
      health and disease. METHODS: Fresh adult porcine and ovine hearts were passively
      pumped to simulate normal cardiac motion at stroke volumes (SVs) varying from 30
      to 70 mL. A 3V-D Matrix probe, interfaced with a GE Vivid E9 ultrasound system,
      was used to image each heart at baseline conditions and after simulated
      myocardial infarction (MI). The 4D LV quantification function of EchoPAC PC was
      used to quantify the LVM and longitudinal and circumferential strain (LS & CS) of
      LV segments at each SV prior and subsequent to simulated MI. LVM was validated by
      volumetric displacement, while LS and CS values were compared to sonomicrometry
      based strain. RESULTS: Linear regression analyses show excellent correlations in
      LVM, LS, and CS between the 4D echo and volumetric/sonomicrometric displacement
      with R(2) values of 0.99, 0.88, and 0.67, respectively. Bland-Altman analyses for
      all variables validate the compatibility of both methods. It was also determined
      that EchoPAC PC was able to detect a decrease in LS and CS in the relevant
      segments between pre- and post-MI at all SVs (P < 0.05). CONCLUSIONS: EchoPAC PC
      is a robust utility with the ability to accurately obtain quantitative LVM, LS,
      and CS values from 4D echo volumes and has the potential to improve the yield of
      clinical studies in cases of suspected MI.

PMID- 24930504
TI  - Immunomodulatory and potential therapeutic role of mesenchymal stem cells in
      periodontitis.
AB  - Periodontitis is a chronic inflammatory disease leading to alveolar bone
      destruction, and eventually tooth loss. In genetically or environmentally
      predisposed individuals periodontopathogenic bacteria trigger an inflammatory
      immune response where activated macrophages secrete inflammatory cytokines and T
      helper 17 cells produce interleukin-17, receptor activator of nuclear factor
      kappa B ligand (RANKL) and tumor necrosis factor-alpha. Inflammation and the
      production of RANKL, the key cytokine responsible for osteoclast activation,
      cause excessive activation of osteoclasts. This results in a decoupling between
      bone formation and resorption, leading to bone loss. As conventional treatment
      does not target the inflammatory response and osteoclast activation, its
      effectiveness is limited. Novel treatments are thus required if we are to cure
      this disease. Mesenchymal stem cells (MSCs), including those of dental origin,
      are potent immunomodulators and are known to be suitable for tissue regeneration.
      MSCs can inhibit the immune response by suppressing T cells, inducing regulatory
      T cells and converting dendritic cells and macrophages into a regulatory
      phenotype. Additionally, genetic modulation may enhance the therapeutic potential
      of MSCs. In the present review the authors describe the potential use of MSCs,
      either unmodified or engineered for therapeutic purposes in periodontitis, with
      special emphasis on MSCs from dental pulp and periodontal ligament. The paper
      envisions that multiple targeting of this inflammatory disease by modulating the
      immune response, promoting bone regeneration and inhibiting bone resorption might
      yield significantly improved treatment outcomes when combined with conventional
      treatment modalities.

PMID- 24930505
TI  - The current view on biological potency of cationically modified chitosan.
AB  - Chitosan is biocompatible polymer obtained from chitin, the building component of
      the crustacean shells. In this paper we make an attempt to review the current
      state of knowledge on some biological effects of chitosan in comparison with
      those of cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium
      chitosan chloride (HTCC) that was recently synthetized by us by covalent
      attachment of glycidyltrimethylammonium chloride (GTMAC). Biological effects of
      HTCC and non-modified polymer are very similar. However, HTCC shows some unique
      beneficial properties which have not been found in its non-modified counterpart.
      One such example is that HTCC has the ability to bind heparin at physiological
      pH. HTCC having the degree of substitution almost 63.6% is easily absorbed within
      1 hour after oral administration as found in C57BL/6j mice using FITC-labeled
      polymer. HTCC is distributed to lung, heart, and kidneys. HTCC stimulates and
      enhances blood platelet aggregation and decreases erythrocyte deformability
      (RBC). Moreover, HTCC seems to decrease both plasma total cholesterol level and
      LDL-cholesterol level in apoE-knockout mice fed with a diet containing HTCC. HTCC
      possibly down-regulates the HMG-CoAR mRNA level after 24 hour incubation with
      HepG2 cells in vitro.

PMID- 24930506
TI  - Exendin-4, an analogue of glucagon-like peptide-1, attenuates hyperalgesia
      through serotonergic pathways in rats with neonatal colonic sensitivity.
AB  - Glucagon-like peptide-1 (GLP-1) analogue ROSE-010 can provide effective pain
      relief from irritable bowel syndrome (IBS). However, the underlying biological
      mechanism is still unknown. Here, we investigate the effect of GLP-1 analogue
      exendin-4 on visceral hypersensitivity in colonic sensitized rats. Rat models of
      visceral hypersensitivity were established by intra-colonic infusion of acetic
      acid in 10-day-old Sprague-Dawley rats. Visceral sensitivity was assessed by
      measurement of abdominal withdrawal reflex (AWR) and electromyography (EMG).
      Exendin-4 with doses of 1, 5, and 10 MUg/kg were intraperitoneally administered,
      respectively. The expressions of serotonin transporter (SERT) and tryptophan
      hydroxylase-1 (TPH-1) in colonic tissues were detected by RT-PCR and Western
      blot, respectively. The levels of serotonin (5-HT) and GLP-1 were measured by
      ELISA assay. Visceral hypersensitivity after neonatal colonic sensitization was
      verified. The colonic sensitized rats showed low levels of GLP-1 in plasma and
      high levels of 5-HT in plasma and colonic tissue (P<0.05). Exendin-4 dose
      dependently reduced visceral hypersensitivity in colonic sensitized rats. The AWR
      scores in colonic sensitized rats with exendin-4 (5 MUg/kg) reduced to 1.56+/
      0.53 (P=0.013 vs. 2.33+/-0.50), 2.23+/-0.45 (P=0.008 vs. 3.0+/-0.5) during CRD at
      40, and 60 mmHg, respectively. Similar findings were showed at dose of 10 MUg/kg.
      Exendin-4 (5 MUg/kg and 10 MUg/kg) reduced the EMG during CRD at 40, 60, 80 mmHg
      (P<0.01). Exendin-4 (5.0 MUg/kg or 10.0 MUg/kg) significantly decreased the 5-HT
      colonic levels (2.343+/-0.447, 2.175+/-0.360 ng/100 mg vs. 3.607+/-0.628 ng/100
      mg, P<0.05). The SERT protein expressions in colonic tissues in colonic
      sensitized rats were significantly increased with exendin-4 at doses of 1, 5 or
      10 MUg/kg (0.759+/-0.068, 0.942+/-0.037, 0.944+/-0.097 vs. 0.552+/-0.047, P<0.05,
      respectively), and the SERT mRNA expression also increased after treatment with
      exendin-4. The colonic sensitized rats showed lower TPH-1 levels after treatment
      with exendin-4 (P<0.05). These findings suggest that exendin-4 reduce visceral
      hypersensitivity and this may be associated with up-regulating SERT expression,
      and down-regulating TPH-1 expression.

PMID- 24930507
TI  - Evaluation of hyperprolactinaemia with the use of the intervals for prolactin
      after macroforms separation.
AB  - Macroprolactin (MaPRL) - a complex of monomeric prolactin (PRL) with
      immunoglobulin G, may be a cause of laboratory diagnosed hyperprolactinaemia. To
      quantify MaPRL, a precipitation with polyethylene glycol may be performed. This
      method involves calculating of recovery ratio but the cut-off value is not
      precisely determined. Moreover, it is proposed that the assessment of
      macroprolactinaemia should include also the evaluation of real PRL concentration
      which means the level of the hormone after macroforms separation. The study
      included 245 patients with hyperprolactinaemia, in whom precipitation was
      performed. A recovery ratio <=40% indicated macroprolactinaemia. The real PRL
      concentrations of the studied subjects were compared with reference ranges
      suggested by the assay manufacturer and with new intervals for PRL after
      macroforms separation. On the base of the recovery ratio after the precipitation,
      macroprolactinaemia was detected in 21 persons. In these patients true
      hyperprolactinaemia (elevation of real PRL concentration above manufacturer's
      reference ranges) was noted in 9 cases. Among 224 patients with a recovery >40%,
      real PRL concentration turned out to be within the manufacturer's reference range
      (pseudohyperprolactinaemia) in 36 persons. The new intervals for PRL after
      macroforms separation were about 20% lower than the manufacturer's reference
      ranges. After applying new ranges in patients with macroprolactinaemia, true
      hyperprolactinaemia was observed in 14 persons, while in the group without MaPRL
      dominance, pseudohyperprolactinaemia was noted in 5 patients. The use of the
      recovery ratio only to recognize macroprolactinaemia may lead in some subjects to
      the misclassification of the results. For that reason the assessment of the PRL
      concentration after macroforms separation that can help to distinguish true
      hyperprolactinaemia and pseudohyperprolactinaemia, seems to be reasonable. To
      evaluate the real PRL concentration, the reference intervals suggested by the
      manufacturer of immunoassay might be used. However, possibly better means to
      diagnose patients with hyperprolactinaemia accurately is using an appropriate
      range for the concentration of PRL after macroforms separation.

PMID- 24930508
TI  - Matrix metalloproteinase 9/neutrophil gelatinase associated lipocalin/tissue
      inhibitor of metalloproteinasess type 1 complexes are localized within
      cardiomyocytes and serve as a reservoir of active metalloproteinase in porcine
      female myocardium.
AB  - Matrix metalloproteinase 9 (MMP-9) is crucial for physiological tissue repair and
      pathophysiological myocardial remodeling. The regulation of its functioning has
      been shown to be mediated by formation of complexes with tissue inhibitor of
      metalloproteinases 1 (TIMP-1) and neutrophil gelatinase associated lipocalin
      (NGAL). We investigated the mRNA and protein expression of MMP-9, TIMP-1 and
      NGAL, the formation of complexes, their gelatinolytic activity and cellular
      localization in left ventricle (LV) from 10 female pigs with induced systolic
      heart failure (HF), 5 control pigs, and a woman with severe HF. The MMP-9, TIMP-1
      and NGAL mRNA in LV did not differ between diseased and healthy pigs. In all pigs
      MMP-9, TIMP-1 and NGAL proteins were present in LV as high molecular weight (HMW)
      complexes (115, 130, 170 and 220 kDa), and no monomers were found. A 80 and 115
      kDa gelatinolytically active bands were present in all LV homogenates. A 130-kDa
      active band was seen only in LV from pigs with severe HF. Similar results were
      found in the explanted heart of a female patient with severe HF. The incubation
      of the homogenates of porcine LV at 37 degrees C resulted in appearance of 88 kDa
      active band, which was accompanied by a decreased intensity of HMW bands. The
      incubation of the homogenates of porcine LV (depleted of active MMP-9) with
      trypsin generated 80 and 115 kDa active bands. Immunohistochemistry revealed the
      presence of MMP-9 in the cytoplasm of porcine cardiomyocytes, but not in
      cardiofibroblasts. Our data suggest that MMP-9 originates from cardiomyocytes,
      forms the gelatinolytically inactive complexes with TIMP-1 and NGAL, present in
      normal and failing myocardium, likely serving as a reservoir of active MMP-9.
      Further studies are needed to elucidate the role of these HMW complexes in the
      extracellular matrix remodeling during the progression of HF, which presence
      should be considered when developing efficient strategies inhibiting myocardial
      matrix metalloproteinases.

PMID- 24930509
TI  - Elevated serum osteoprotegerin is associated with decreased osteoclastic
      differentiation in stenotic aortic valves.
AB  - Calcific aortic valve stenosis (CAVS) is an actively regulated process that
      involves mechanisms of bone development, including the receptor activator of
      nuclear factor kappaB, its ligand, and osteoprotegerin (RANK/RANKL/OPG)
      regulatory system. The aim of this study was to investigate whether the levels of
      circulating OPG and RANKL can be correlated with some histopathological features
      of the stenotic valves. Serum levels of osteoprotegerin (OPG) and soluble RANKL
      (sRANKL) were assessed in 27 patients with CAVS prior to valve replacement
      surgery and in 12 control subjects. The removed valves were examined
      macroscopically and microscopically. Valve sections were stained with hematoxylin
      and eosin for general morphology, with Oil Red O for lipids and immunostained
      with antibodies against markers visualizing osteoclastic cells (tartrate
      resistant acid phosphatase, TRAP), macrophages (CD68) and blood vessels (CD34).
      Patients with CAVS had elevated levels of OPG as compared to the control group
      (p=0.005). Within the CAVS group, patients with osteoclastic TRAP-positive cells
      in their valves had significantly lower serum levels of OPG (p=0.009) and lipid
      content (p=0.03) than those without such cells. Moreover, osteogenic metaplasia
      was observed exclusively in the valves containing TRAP-positive cells. Results of
      this study suggest that the circulating OPG can influence the processes occurring
      in the calcifying valves by inhibiting osteoclastic differentiation of cells
      involved in calcification and by preventing osteogenic metaplasia.

PMID- 24930510
TI  - The prevention of ischemia/reperfusion induced oxidative damage by venous blood
      in rabbit kidneys monitored with biochemical, histopatological and
      immunohistochemical analysis.
AB  - The purpose of this study was to investigate the biochemical, histopathological
      and immunohistochemical effects of venous blood on ischemia/reperfusion-induced
      oxidative DNA damage and mutation in rabbit kidneys in comparison to melatonin
      treatment, which has a known protective effect against ischemia/reperfusion (IR)
      injury. The rabbits were divided into five groups: renal ischemia (RI), renal
      ischemia-reperfusion (RIR), renal ischemia-venous blood-reperfusion (RIVR),
      melatonin + renal ischemia-reperfusion (MRIR), and the healthy sham control group
      (HG). Melatonin (2.5 mg/kg delivered intraperitoneally) was administered one hour
      prior to ischemia. In the RIVR group, 1 ml of venous blood was administered 5
      minutes before the reperfusion. The xanthine oxidase activity in the kidney
      tissue was determined as 53.50 +/- 1.72, 31.00 +/- 6.39, 45.66 +/- 9.20, 28.66 +/
      6.05 and 14.33 +/- 1.28 U/g protein; the MDA levels were 6.32 +/- 0.02, 19.50 +/
      1.33, 7.00 +/- 0.96, 7.50 +/- 0.76 and 4.75 +/- 0.34 mmol/g protein; and the GSH
      levels were 4.50 +/- 1.08, 2.76 +/- 0.13, 5.48 +/- 0.22, 4.93 +/- 0.55 and 6.98
      +/- 0.33 nmol/g protein in the RI, RIR, RIVR, MRIR and HG groups, respectively.
      Blood, blood urea nitrogen (BUN) and creatinine levels were classified as high
      only in the RIR group. The MRIR and RIVR groups, in which oxidative stress was
      best suppressed, had much milder histopathological and immunohistochemical
      findings compared to the RIR group. This study has revealed that it is useful to
      initiate reperfusion of the ischemic tissue with venous blood.

PMID- 24930511
TI  - Role of nitrergic and endothelin pathways modulations in cisplatin-induced
      nephrotoxicity in male rats.
AB  - Although the protective role of either nitric oxide (NO) or endothelin (ET)
      receptors modulation on the severity of cisplatin-induced nephrotoxicity has been
      recognized in previous studies including our own, the possible interaction
      between the two pathways remains obscure. In this study, we tested for the first
      time the possible interaction between the nitrergic and endothelin pathways in
      cisplatin-induced nephrotoxicity in male rats. Sprague Dawley male rats were
      divided into four groups: control (given a single dose of normal saline, i.p.),
      cisplatin (6 mg/kg, i.p.), cisplatin + sildenafil (2 mg/kg, i.p.), cisplatin +
      sildenafil + BQ-123 (1 mg/kg, i.p.). Each of the co-administered drugs was given
      in two doses; one hour before and one day after the cisplatin dose. Acute
      cisplatin administration resulted in significant increases in blood urea nitrogen
      (BUN) and serum creatinine levels at 96 hours following cisplatin injection.
      Increased levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF
      alpha) and caspase-3, decreased nitrite/nitrate level and superoxide dismutase
      (SOD) activity in kidney homogenates were also observed following cisplatin
      injection, in addition to a typical 'acute tubular necrosis' pattern. According
      to the obtained results, the co-adminstration of sildenafil alone with cisplatin
      offered a reno-protective effect comparable to that obtained following the
      concurrent administration of both sildenafil and the selective ET-A receptor
      antagonist BQ-123. Thus, the current study is the first to reveal that the
      presence of an intact NO/cGMP system may offer a moderate reno-protective effect
      against cisplatin-induced nephrotoxicity even in the presence of ET-A-mediated
      vasoconstriction, suggesting the absence of obvious functional interaction
      between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity
      in male rats.

PMID- 24930512
TI  - Cardiovascular effects of methacholine-induced airway obstruction in man.
AB  - Cardiovascular disease is the most frequent cause of death in people with chronic
      respiratory disease. The cause of this association has been attributed to airway
      obstruction leading to cardiovascular dysfunction (increased central blood
      pressure (BP) and aortic stiffness). However, this has never been experimentally
      tested. Methacholine is routinely used to stimulate airway function changes that
      mimic airway pathology. This study aimed to determine the cardiovascular effects
      of methacholine-induced airway obstruction. Fifteen healthy young adults (aged
      22.9+/-2.5 years; 4 male; mean+/-S.D.) underwent a bronchial challenge test
      (randomized, blinded, cross-over design) in which they received nebulized
      methacholine inhalation in serially increasing concentrations (from 0.39 to 25
      mg/ml) or saline (0.9%; control) on two separate days. Bronchoconstriction was
      assessed by forced expiratory volume at one second (FEV1) and cardiovascular
      effects by augmentation index, brachial BP, central BP, heart rate and aortic
      stiffness. Methacholine significantly decreased FEV1 from baseline to peak
      inhaled concentration compared with saline (-0.48+/-0.34 vs. -0.07+/-0.16 L;
      p<0.001), but there was no between-group change in augmentation index (1.6+/-7.0
      vs. 3.7+/-10.2% p=0.49), brachial systolic BP (-3.3+/-7.6 vs. -4.7+/-5.7 mmHg;
      p=0.59), central systolic BP (-1.1+/-5.2 vs. -0.3+/-5.5 mmHg; p=0.73), heart rate
      (0.4+/-7.1 vs. -0.8+/-6.6 bpm; p=0.45) or aortic stiffness (0.2+/-1.3 vs. 0.8+/
      1.8 m/s; p=0.20; n=12). Thus, methacholine induced airway obstruction does not
      acutely change brachial BP or central haemodynamics. This finding refutes the
      notion that airway obstruction per se leads to cardiovascular dysfunction, at
      least in healthy individuals in the acute setting.

PMID- 24930513
TI  - Effects of gadolinium chloride on basal flow and compression-induced rapid
      hyperemia in the rabbit masseter muscle.
AB  - Aim of the present study is to investigate the role of mechano-sensitive channels
      on basal muscle blood flow and on the compression-induced rapid hyperaemia. To
      this aim, the mechano-sensitive channel blocker Gadolinium (Gd(3+)) is employed,
      which already proved to reduce the myogenic response in isolated vessels. Muscle
      blood flow (MaBF) was recorded from the masseteric artery in 8 urethane
      anesthetized rabbits. Rapid hyperemic responses were evoked by 1-s lasting
      compressions of the masseter muscle (MC) delivered before and after close
      arterial infusion of Gd(3+) in the masseteric artery. Three infusions were
      performed at 1-h interval, producing estimated plasma concentration (EPC) of
      0.045, 0.45 and 4.5 mM, in the masseteric artery. The amplitude of the hyperaemic
      response to MC, equal to 195+/-77% of basal flow in control condition, was
      reduced by 9.5+/-19.4% (p=0.18) and 45+/-28% (p<0.01) while basal MaBf increased
      by 10+/-3% (p=0.90) and by 68+/-30% (p<0.01) at EPC of 0.045 and 0.45 mM,
      respectively. At EPC of 4.5 mM a strong reduction in both MaBF (by 54+/-13%,
      p<0.01) and MC response (75+/-12%, p<0.01) was instead observed. These effects
      did not depend on time from infusion. At all doses employed Gd(3+) never affected
      arterial blood pressure, heart rate and contralateral MaBF. While the effects
      observed at the highest EPC likely result from blood vessel occlusion due to
      Gd(3+) precipitation, the effects observed at lower concentrations demonstrate
      that Gd(3+) affects musculo-vascular function by decreasing both resting vascular
      tone and responsiveness to mechanical stimuli. The results are compatible with a
      Gd(3+)-induced blockade of vascular mechano-sensitive channels.

PMID- 24930515
TI  - Inhibition of phosphodiesterase 3B in insulin-secreting cells of normal and
      streptozocin-nicotinamide-induced diabetic rats: implications for insulin
      secretion.
AB  - Cyclic adenosine monophosphate (cAMP) plays important role in the potentiation of
      insulin secretion in pancreatic B-cells. However, the relevance of cAMP-degrading
      enzymes in the regulation of insulin secretion is not fully elucidated. The
      present work was undertaken to determine effects of inhibition of
      phosphodiesterase 3B (PDE3B) by amrinone on insulin secretion from pancreatic
      islets and perfused pancreas of normal and mildly diabetic rats. Inhibition of
      this enzyme was demonstrated to substantially increase insulin-secretory response
      to 6.7 mM glucose in the isolated islets and perfused pancreas of non-diabetic
      rats. Increment in glucose-induced insulin secretion resulting from inhibition of
      PDE3B was accompanied by an increase in islet cAMP levels and was suppressed by
      inhibition of protein kinase A. It was also demonstrated that insulin secretion
      stimulated by glucose and 1 MUM forskolin was only slightly elevated in the
      presence of amrinone. Moreover, insulin release induced by succinate instead of
      glucose was also augmented by inhibition of PDE3B in rat islets. However,
      exposure of the pancreatic islets of streptozotocin-nicotinamide-induced diabetic
      rats to amrinone appeared to be without any effect on glucose-induced insulin
      secretion. Similar lack of response was shown in the perfused pancreas of
      diabetic rats. These results indicate that inhibition of PDE3B by amrinone
      significantly augments insulinotropic action of physiological glucose in B-cells
      of normal rats. This effect is mediated via protein kinase A and may be also
      induced in the presence of metabolizable stimuli other than glucose. Effects
      generated by amrinone were demonstrated to be, however, insufficient to enhance
      glucose-induced insulin secretion in B-cells of streptozotocin-nicotinamide
      induced diabetic rats.

PMID- 24930514
TI  - Cardiovascular effects of ethanol extract of Rubus chingii Hu (Rosaceae) in rats:
      an in vivo and in vitro approach.
AB  - Rubus chingii Hu (Rosaceae) is an important traditional Chinese medicine that has
      been used to improve function of the kidney and treat excessive polyuria.
      However, the effects of Rubus chingii on the cardiovascular system and its
      pharmacological mechanisms of action have not been studied. The aim of the
      present study was to evaluate the cardiovascular effects of ethanol extract of
      Rubus chingii (ERC) in rats. The changes in systolic blood pressure and heart
      rate of rats and vascular tone of aortic rings in in vitro were measured using
      pressure transducer and force transducer, respectively, connected to a
      multichannel recording system. ERC decreased systolic blood pressure and heart
      rate in a concentration-dependent manner. ERC induced vasorelaxation in a
      concentration-dependent manner. The ERC-induced vasorelaxation was not observed
      in the absence of the endothelium. The vasorelaxant effect of ERC was
      significantly attenuated by inhibition of endothelial NO synthase (eNOS), soluble
      guanylyl cyclase (sGC), or Ca(2+) entry from extracellular sources with L-NAME,
      ODQ, diltiazem, or extracellular Ca(2+) depletion, respectively. Similarly, an
      inhibition of Akt with wortmannin attenuated the ERC-induced vasorelaxation.
      Modulators of the store-operated Ca(2+) entry, thapsigargin, Gd(3+), and 2
      aminoethyl diphenylborinate markedly attenuated the ERC-induced vasorelaxation.
      Furthermore, 4-aminopyridine an inhibitor of voltage-dependent K(+) (KV) channel,
      significantly attenuated the ERC-induced vasorelaxation. However,
      tetraethylammonium and glibenclamide, had no significant effect on the ERC
      induced vasorelaxation. Indomethacin, atropine, and propranolol had no effects on
      the ERC-induced vasorelaxation. The present study demonstrates that ERC induces
      vasorelaxation via endothelium-dependent two-step signaling: an activation of the
      Ca(2+)-eNOS-NO signaling in the endothelial cells and then subsequent stimulation
      of the NO-sGC-cGMP-KV channel signaling in the vascular smooth muscle cells. The
      Akt-eNOS pathway is also suggested to be involved in this relaxation. Also, the
      findings suggest that the ERC-induced vasorelaxation is closely related to the
      hypotensive action of the agent.

PMID- 24930516
TI  - Indomethacin-induced generation of reactive oxygen species leads to epithelial
      cell injury before the formation of intestinal lesions in mice.
AB  - Recently, with the increasing number of elderly patients who continuously take
      aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs), the number of cases
      of severe hemorrhagic gastrointestinal (GI) bleeding is also on the increase.
      Gastric acid has been reported to play the most important role in hemorrhagic
      gastric mucosal injury. However, the pathogenesis of NSAID-derived mucosal injury
      in the intestine, where there is no acidic environment, remains unknown. We
      previously reported that NSAID-derived mitochondrial reactive oxygen species
      (ROS) are directly involved in GI cellular injury in vitro, although an in vivo
      study has not yet been carried out. In this study, we investigated the
      relationship between NSAID-derived ROS and intestinal injury formation. For this
      purpose, intestinal mucosal live imaging in mice was carried out using an ROS
      indicating fluorescent probe. Treatment with indomethacin caused macroscopic
      intestinal injury in mice; however, many dying cells were observed even in areas
      that macroscopically appeared to have no injury after treatment with
      indomethacin. A fluorescent probe revealed that mucosal cells in the apparently
      uninjured areas had a high concentration of ROS. Treatment with rebamipide
      significantly decreased both the ROS concentration and the number of dying cells:
      this drug is prescribed clinically for gastric injury patients and has been
      reported to upregulate the expression of manganese superoxide dismutase. On the
      basis of these results, we propose that NSAID treatment causes a high cellular
      concentration of ROS in mucosae, possibly decreasing mucosal organo-protective
      efficacy. Moreover, intestinal food contents are likely to damage the mucosal
      structure when it is in such a fragile condition.

PMID- 24930517
TI  - Moderate-intensity interval training increases serum brain-derived neurotrophic
      factor level and decreases inflammation in Parkinson's disease patients.
AB  - It has been demonstrated that physical training increases serum brain-derived
      neurotrophic factor (BDNF) in healthy people. The aim of this study was to
      establish the effect of physical training on the basal serum level of the BDNF in
      the Parkinson's disease patients (PD patients) in relation to their health
      status. Twelve PD patients (mean +/- S.E.M: age 70 +/- 3 years; body mass 70 +/-
      2 kg; height 163 +/- 3 cm) performed a moderate-intensity interval training
      (three 1-hour training sessions weekly), lasting 8 weeks. Basal serum BDNF in the
      PD patients before training amounted to 10,977 +/- 756 pg x mL(-1) and after 8
      weeks of training it has increased to 14,206 +/- 1256 pg x mL(-1) (i.e. by 34%,
      P=0.03). This was accompanied by an attenuation of total Unified Parkinson's
      Disease Rating Scale (UPDRS) (P=0.01). The training resulted also in a decrease
      of basal serum soluble vascular cell adhesion molecule 1 (sVCAM-1) (P=0.001) and
      serum tumor necrosis factor-alpha (TNF-alpha) (P=0.03) levels. We have concluded
      that the improvement of health status of the Parkinson's disease patients after
      training could be related to the increase of serum BDNF level caused by the
      attenuated inflammation in those patients.

PMID- 24930518
TI  - One session of exercise or endurance training does not influence serum levels of
      irisin in rats.
AB  - Irisin induces the browning of adipose tissue. The goal of this study was to
      investigate the influence of acute exercise in untrained and trained rats and
      endurance training on FNDC5 mRNA and irisin levels in white and red skeletal
      muscle and serum. Rats (n=60) were randomly divided into two groups: untrained
      and trained (subjected to 6-week endurance training with increasing load).
      Subgroups of rats from each group were sacrificed before (controls), immediately
      after, or 3 hours following acute exercise with the same work load. Muscle
      samples (red and white) and serum were collected. FNDC5 mRNA was evaluated using
      RT-PCR. Irisin levels were measured using an immunoenzymatic method. Muscle FNDC5
      mRNA decreased immediately after acute exercise compared with baseline levels,
      but not in red muscle in trained rats. Atrend toward a return to baseline
      appeared 3 hours after the exercise, but only in white muscle in untrained group.
      Irisin protein levels increased after acute exercise in red muscle 3 hours post
      exercise compared with samples taken immediately after exercise, and decreased 3
      hours post-exercise compared to pre-exercise level in white muscles. FNDC5 mRNA
      did not change following training, whereas irisin protein levels increased in red
      muscle and decreased in white muscle. Serum irisin levels remained unchanged
      following acute exercise and training. We concluded that changes in irisin mRNA
      and protein levels in rat muscle after acute exercise are limited and depend on
      training status and the muscle type. Irisin serum levels remained stable after
      acute exercise or endurance training.

PMID- 24930519
TI  - Novel treatment options in stage I non-small-cell lung cancer.
AB  - In the last 5 years, the current management of stage I non-small-cell lung cancer
      has been challenged due to novel surgical approaches and advances in radiation
      technology. The outcome after a sublobar resection is promising, especially for
      tumors less than 2 cm. Other treatment opportunities are available for high risk
      patients with comorbidity and impaired pulmonary function. Stereotactic ablative
      body radiotherapy is a good alternative treatment to surgery, especially in
      elderly and comorbid patients. However, randomized evidence comparing sublobar
      resection and stereotactic radiotherapy is presently lacking. The most recent
      development in radiotherapy is hadron therapy with a presumed reduced toxicity
      because of its peculiar physical and biological effects. Promising thermal and
      microwave ablative techniques are in development and have specific niche
      indications. 

PMID- 24930521
TI  - Suicides in the military: the post-modern combat veteran and the Hemingway
      effect.
AB  - Suicides in the military have increased over the last ten years. Much effort has
      been focused on suicide prevention and treatment, as well as understanding the
      reasons for the sharp increase in military suicides. Despite this effort, the
      definitive causes of military suicides remain elusive. Further, highly effective
      suicide prevention and treatment approaches have not yet been developed. The
      purpose of this article is to present a short review of the current state of
      suicide prevention interventions within the context of the military. The root
      causes of suicidal behavior and the role of combat in the military are each
      discussed. Interpersonal-psychological theory of suicide and the military
      transition theory are introduced as guiding frameworks for understanding suicides
      and suicidal behavior amongst active military personnel and military veterans.
      The article concludes with a set of recommendations for moving forward in
      understanding and addressing suicides in the military.

PMID- 24930520
TI  - An in vivo role for Rho kinase activation in the tumour vascular disrupting
      activity of combretastatin A-4 3-O-phosphate.
AB  - BACKGROUND AND PURPOSE: Combretastatin A-4 3-O-phosphate (CA4P) is in clinical
      trial as a tumour vascular disrupting agent (VDA) but the cause of blood flow
      disruption is unclear. We tested the hypothesis that activation of Rho/Rho kinase
      (ROCK) is fundamental to the effects of this drug in vivo. EXPERIMENTAL APPROACH:
      Mouse models of human colorectal carcinoma (SW1222 and LS174T) were used. Effects
      of the ROCK inhibitor, Y27632, alone or in combination with CA4P, on ROCK
      activity, vascular function, necrosis and immune cell infiltration in solid
      tumours were determined. Mean arterial BP (MABP) was measured to monitor systemic
      interactions and the vasodilator, hydralazine, was used to control for the
      hypotensive effects of Y27632. KEY RESULTS: Y27632 caused a rapid drop in blood
      flow in SW1222 tumours, with recovery by around 3 h, which was paralleled by MABP
      changes. Y27632 pretreatment reduced CA4P-induced ROCK activation and partially
      blocked CA4P-induced tumour vascular effects, in both tumour types. Y27632 also
      partially inhibited CA4P-induced tumour necrosis and was associated with reduced
      immune cell infiltration in SW1222 tumours. Hydralazine caused a similar
      hypotensive effect as Y27632 but had no protective effect against CA4P treatment.
      CONCLUSIONS AND IMPLICATIONS: These results demonstrate that ROCK activity is
      critical for full manifestation of the vascular activity of CA4P in vivo,
      providing the evidence for pharmacological intervention to enhance the anti
      tumour efficacy of CA4P and related VDAs.

PMID- 24930524
TI  - Choosing Wisely((r)) in pulmonary medicine.

PMID- 24930522
TI  - Problems in the boundaries of bipolar disorders.
AB  - Classical concepts of bipolarity (bipolar I and bipolar II) have sometimes been
      extended into a broader spectrum that includes a wide variety of conditions
      previously diagnosed as separate forms of psychopathology. Differential diagnosis
      remains important, particularly in personality disorders characterized by
      affective instability, and in behavior disorders affecting pre-pubertal children.
      In the absence of biological markers or other external sources of validity, as
      well as lack of evidence for response to pharmacological treatment when disorders
      are defined more broadly, the bipolar spectrum remains an unproven hypothesis.

PMID- 24930525
TI  - Endothelial progenitor cells for acute respiratory distress syndrome treatment:
      support your local sheriff!

PMID- 24930526
TI  - A step forward toward the clinical application of palifermin for acute
      respiratory distress syndrome?

PMID- 24930527
TI  - The challenge of reducing smoking in low-income parents.

PMID- 24930528
TI  - Science as observation and experiment: examining the role of sleep apnea and
      continuous positive airway pressure treatment in cardiovascular outcomes.

PMID- 24930530
TI  - Air embolism via a bronchoventricular fistula.

PMID- 24930531
TI  - Treatment of group I pulmonary arterial hypertension with carvedilol is safe.

PMID- 24930529
TI  - Update in asthma 2013.

PMID- 24930533
TI  - The hemodynamic effects of prone positioning in patients with acute respiratory
      distress syndrome remain to be defined.

PMID- 24930534
TI  - Reply: Prone positioning actually exerts benefits on hemodynamics!

PMID- 24930532
TI  - Plasma complement levels are associated with primary graft dysfunction and
      mortality after lung transplantation.

PMID- 24930535
TI  - Reply: Reply: Prone positioning actually exerts benefits on hemodynamics!

PMID- 24930536
TI  - Palliative care: a core competency for intensive care unit doctors.

PMID- 24930538
TI  - Reply: Palliative care: a core competency for intensive care unit doctors.

PMID- 24930539
TI  - Discrepancy between dual-energy computed tomography lung perfusion blood volume
      and lung perfusion single-photon emission computed tomography/computed tomography
      images in pulmonary embolism.

PMID- 24930540
TI  - Tracheobronchial calcification due to warfarin therapy.

PMID- 24930541
TI  - Obesity and asthma: "What we've got here is failure to communicate".

PMID- 24930542
TI  - Lung cancer.

PMID- 24930543
TI  - Impairments in learning by monetary rewards and alcohol-associated rewards in
      detoxified alcoholic patients.
AB  - BACKGROUND: Excessive alcohol consumption has been linked to structural and
      functional brain changes associated with cognitive, emotional, and behavioral
      impairments. It has been suggested that neural processing in the reward system is
      also affected by alcoholism. The present study aimed at further investigating
      reward-based associative learning and reversal learning in detoxified alcohol
      dependent patients. METHODS: Twenty-one detoxified alcohol-dependent patients and
      26 healthy control subjects participated in a probabilistic learning task using
      monetary and alcohol-associated rewards as feedback stimuli indicating correct
      responses. Performance during acquisition and reversal learning in the different
      feedback conditions was analyzed. RESULTS: Alcohol-dependent patients and healthy
      control subjects showed an increase in learning performance over learning blocks
      during acquisition, with learning performance being significantly lower in
      alcohol-dependent patients. After changing the contingencies, alcohol-dependent
      patients exhibited impaired reversal learning and showed, in contrast to healthy
      controls, different learning curves for different types of rewards with no
      increase in performance for high monetary and alcohol-associated feedback.
      CONCLUSIONS: The present findings provide evidence that dysfunctional processing
      in the reward system in alcohol-dependent patients leads to alterations in reward
      based learning resulting in a generally reduced performance. In addition, the
      results suggest that alcohol-dependent patients are, in particular, more impaired
      in changing an established behavior originally reinforced by high rewards.

PMID- 24930544
TI  - Does the use of lapatinib increase the risk of fatigue and hepatic toxicities in
      patients with solid tumors? A critical literature review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis of fatigue and hepatic adverse
      events associated with lapatinib use in solid tumor patients were performed.
      RESEARCH DESIGN AND METHODS: Eligible studies included randomized Phase II and
      III trials of patients with solid tumors taking lapatinib. They described events
      of fatigue, elevated alanine aminotransferase (ALT), aspartate aminotransferase
      (AST) and total bilirubin. Our search yielded 380 potentially relevant citations
      on lapatinib from PubMed/Medline, CENTRAL Cochrane registry and ASCO meeting
      library. RESULTS: After exclusion of ineligible studies, a total of 15 clinical
      trials were included in the meta-analysis. The relative risk (RR) of all-grade
      fatigue, elevated ALT, AST and total bilirubin were 0.99 (95% CI 0.87 - 1.13; p =
      0.87), 1.12 (95% CI 0.87 - 1.44; p = 0.55), 0.79 (95% CI 0.43 - 1.45; p = 0.44),
      5.17 (95% CI 0.18 - 149.81; p = 0.34), respectively. Exploratory subgroup
      analysis showed no effect of comparator regimen on the RR of the relevant adverse
      events. CONCLUSIONS: This meta-analysis demonstrated that the evidence for a true
      increased risk of hepatotoxicity or fatigue with lapatinib-based treatment
      compared to control is not yet fully convincing. Future studies should
      investigate this risk further. Clinicians must be aware of these risks and
      perform regular clinical monitoring.

PMID- 24930545
TI  - Similar success rates for single and multiple debridement surgery for acute hip
      arthroplasty infection.
AB  - BACKGROUND: Treatment of an acute total hip arthroplasty (THA) infection aims at
      control of the infection with retention of the implant by surgical debridement
      and antibiotic treatment. There is no clear evidence whether a single surgical
      debridement is sufficient or whether multiple procedures are necessary for
      optimal treatment. METHODS: From a prospective database of patients with acute
      THA infection, we retrospectively reviewed 68 patients treated in 2 large
      teaching hospitals. Hospital S used a protocol in which each patient received a
      single surgical debridement and only additional surgery if infectious symptoms
      persisted (group S; n = 33). In hospital M, patients always received multiple
      surgical debridements (group M; n = 35). Both groups received systemic antibiotic
      treatment. Removal of the implant or persistent infection at follow-up was
      considered failure of treatment. Mean follow-up of the patients was 5 (2-11)
      years. RESULTS: Mean time between implantation and debridement was 19 days. 4
      patients in group S were considered failure, as opposed to 10 patients in group M
      (p = 0.09). 9 patients in group S had additional surgery, which resulted in 3 of
      the 4 failures. At final follow-up, 30 patients in group S and 33 patients in
      group M had a good clinical result (p = 0.6). INTERPRETATION: In patients with
      acute THA infection, a single debridement with only additional surgery on
      indication appears to be at least as successful for retention of the primary
      implant and control of infection as a strategy with multiple surgical
      debridements.

PMID- 24930547
TI  - Open study evaluating the onset of antipsychotic action of olanzapine in the
      treatment of patients with schizophrenia, schizophreniform or schizo-affective
      disorder.
AB  - OBJECTIVE This 6-week, open-label study with olanzapine was designed to determine
      the onset of antipsychotic action of a 10-mg/day starting dose of olanzapine,
      continued as a fixed dose for at least 4 weeks. METHODS A total of 306 patients
      experiencing an acute exacerbation of schizophrenia were prospectively followed
      up. Response was defined as a 20% improvement on the Positive And Negative
      Syndrome Scale (PANSS) positive score, sustained until week 6. Onset of action
      was defined as the time point at which a 20% improvement in positive symptoms
      occurred and was maintained to week 6. RESULTS Significant improvements from
      baseline were observed throughout the study with respect to PANSS positive and
      PANSS total score (P<0.001). Within the first week of treatment, 20.6% of
      patients showed a 20% decrease in PANSS positive score, which was maintained
      until week 6. By weeks 2, 3 and 4 the percentage of responders had risen to 38.2,
      49.7 and 52.3%, respectively. Olanzapine 10 mg/day was well tolerated, with the
      frequency of extrapyramidal symptoms and sexual dysfunction markedly lower
      following treatment than at baseline. CONCLUSION In this clinical open study,
      about half of the patients showed a response within 3 weeks, which is at least
      maintained until week 6. 

PMID- 24930548
TI  - A prospective randomized single-blind, multicenter trial comparing the efficacy
      and safety of paroxetine with and without quetiapine therapy in depression
      associated with anxiety.
AB  - OBJECTIVE To evaluate quetiapine as an adjunct to paroxetine in patients with
      comorbid depression and anxiety. METHOD Prospective, multicenter, single-blind
      trial of patients with DSM-IV major depression and associated anxiety, who were
      randomized to an 8-week treatment with paroxetine alone (n=54) or
      paroxetine+quetiapine (n=58). Quetiapine was dosed to 200 mg/day and paroxetine
      to 60 mg/day, as required. RESULTS Decrease in HAM-A scores was significantly
      greater in the combined therapy group than with paroxetine alone at weeks 2, 4, 6
      and LOCF (P<0.008). Decrease in HAM-D scores was significantly greater in the
      combined therapy group than with paroxetine alone throughout the study period
      (P<0.008). Regarding adverse events, it was found that increases in anxiety and
      insomnia were more prevalent in the paroxetine only group, while increased
      appetite was more prevalent when quetiapine was added (P<0.05). CONCLUSION
      Quetiapine added to paroxetine is well tolerated and may speed up and improve
      response in patients with comorbid depression and anxiety. 

PMID- 24930549
TI  - Predicting factors of depression in patients with primary hypertension: a
      community-based study.
AB  - OBJECTIVE To investigate the factors that may predict the occurrence of
      depression in patients with primary hypertension. METHODS We conducted a cross
      sectional survey on 891 hypertensive patients and 651 normal subjects (control
      group) from a single community. Zung self-rating depression scale (SDS) was
      applied to evaluate the symptoms of depression, which was diagnosed when the SDS
      score was >41. RESULTS There was no significant difference in gender distribution
      (female, 48.5 vs. 47.6%) and age (65.3+/-9.2 vs. 64.0+/-7.9 years) between the
      hypertensive control groups (P>0.05). Depression was diagnosed in 139
      hypertensive patients (15.6%) and 27 (4.2%) control subjects (P<0.01). The
      average SDS score was higher in patients with hypertension duration of more than
      3 years (33.3+/-9.0 vs. 30.6+/-7.6, P<0.001), in patients with severe
      hypertension (44.0+/-7.8 vs. 28.9+/-4.9, P<0.001) and in patients with a history
      of hospitalization for cardiovascular disorders (38.1+/-9.3 vs. 32.0+/-8.4,
      P<0.001). Multivariate regression analysis showed that the degree and the
      duration of hypertension, as well as hospitalization history, were independent
      predictors of depression in the hypertensive patients. CONCLUSIONS Hypertension
      is associated with a higher prevalence of depression that can be predicted by the
      duration and severity of hypertension as well as a history of hospitalization. 

PMID- 24930546
TI  - Metal release and metal allergy after total hip replacement with resurfacing
      versus conventional hybrid prosthesis.
AB  - BACKGROUND: Metal-on-metal (MOM) total hip arthroplasties were reintroduced
      because of the problems with osteolysis and aseptic loosening related to
      polyethylene wear of early metal-on-polyethylene (MOP) arthroplasties. The
      volumetric wear rate has been greatly reduced with MOM arthroplasties; however,
      because of nano-size wear particles, the absolute number has been greatly
      increased. Thus, a source of metal ion exposure with the potential to sensitize
      patients is present. We hypothesized that higher amounts of wear particles result
      in increased release of metal ions and ultimately lead to an increased incidence
      of metal allergy. METHODS: 52 hips in 52 patients (median age 60 (51-64) years,
      30 women) were randomized to either a MOM hip resurfacing system (ReCap) or a
      standard MOP total hip arthoplasty (Mallory Head/Exeter). Spot urine samples were
      collected preoperatively, postoperatively, after 3 months, and after 1, 2, and 5
      years and tested with inductively coupled plasma-sector field mass spectrometry.
      After 5 years, hypersensitivity to metals was evaluated by patch testing and
      lymphocyte transformation assay. In addition, the patients answered a
      questionnaire about hypersensitivity. RESULTS: A statistically significant 10- to
      20-fold increase in urinary levels of cobalt and chromium was observed throughout
      the entire follow-up in the MOM group. The prevalence of metal allergy was
      similar between groups. INTERPRETATION: While we observed significantly increased
      levels of metal ions in the urine during the entire follow-up period, no
      difference in prevalence of metal allergy was observed in the MOM group. However,
      the effect of long-term metal exposure remains uncertain.

PMID- 24930550
TI  - Psychosocial skills training on social functioning and quality of life in the
      treatment of schizophrenia: a controlled study in Turkey.
AB  - OBJECTIVE This study assessed the impact of a psychosocial skills training
      program, consisting of psychoeducation, interpersonal group therapy and family
      education incorporated into social skills training, as an integrative approach on
      social functioning and quality of life of patients with schizophrenia, in
      comparison to standard care for an 8-month period. METHOD Thirty patients with
      DSM-IV schizophrenia were included in the study. Patients were assessed using the
      Positive and Negative Syndrome Scale (PANSS), Quality of Life Scale (QLS), Social
      Functioning Scale (SFS), and Global Assessment of Function (GAF) at baseline.
      Fifteen patients underwent an 8-month psychosocial skills training group program
      and another fifteen patients (waiting list) continued in standard care. Both
      groups were reassessed and analyzed at the end of the study. RESULTS Two groups
      were not statistically different in terms of total PANSS, QLS, SFS, GAF scores,
      and demographic characteristics at baseline. However, there was a significant
      improvement in the mean total QLS, SFS, GAF, and even in total PANSS scores
      (respectively from 64.46+/-19.58 to 89.67+/-24.10, P<0.001, from 93.20+/-22.85 to
      132.60+/-33.85, P<0.002, from 57.40+/-8.78 to 63.86+/-7.57, P<0.012, and from
      63.53+/-14.48 to 53.33+/-15.71, P<0.029) for those who underwent the PSST
      program, but there was no statistically significant change for those on standard
      care at the end of the study. CONCLUSION This study highlights the 'social
      functioning' and 'quality of life' benefits of the psychosocial skills training
      program for patients with schizophrenia. It can be concluded that this
      comprehensive psychosocial skills training program might be an important
      contribution to the functioning of the patients. 

PMID- 24930551
TI  - Characteristics of schizophrenic patients with a history of suicide attempt.
AB  - OBJECTIVE The aim of this study was to evaluate the suicide attempt history among
      schizophrenic patients and compare their sociodemographic and clinical
      characteristics with schizophrenic patients without a history of suicide attempt.
      METHOD Sixty schizophrenic patients according to DSM-IV criteria were included in
      the study. Half of the patients were in acute phase and receiving inpatient
      treatment, while the other half were in stable phase and outpatients. The sample
      was subdivided into two subsamples according to the presence/absence of lifetime
      suicidal attempts. RESULTS History of suicide attempt was found in 27 (45%) of
      the patients. The rate of having suicidal ideation, depression, paranoid type
      schizophrenia and first-degree relatives with psychiatric disorder was high among
      the group with suicide attempt history. Depression and insight scores were high
      and PANSS Negative symptoms subscale score was low among the patients with
      suicide attempt history. There were no significant differences between the two
      groups according to the scores of PANSS Positive symptoms and General
      Psychopathology subscales. CONCLUSION The high rate of suicide attempt history in
      our sample suggests that risk of suicide has to be determined and protective
      measures have to be taken while planning inpatient and outpatient treatment of
      these patients. Suicide attempt history is a risk factor for suicide ideation and
      is also related to depressive symptoms and high insight score and low negative
      symptoms score. 

PMID- 24930552
TI  - Current drug treatment of patients with bulimia nervosa and binge-eating
      disorder: selective serotonin reuptake inhibitors versus mood stabilizers.
AB  - Our aim was to review and compare findings from controlled trials and previous
      reviews concerning current drug treatment of patients suffering from bulimia
      nervosa (BN) and binge eating disorder (BED). Thus we selected published articles
      quoted over the last 10 years in the databases of Medline and Cochrane Library.
      The combination of pharmacological and psychological treatments is superior to
      the single psychotherapeutic approach, which in turn is superior to single drug
      treatment (just superior to placebo). Among drug treatments, SSRIs are the first
      line choice treatments, especially in primary care. They are more acceptable and
      tolerated by patients, moreover effective even if investigations on long-term
      outcomes are lacking. A number of patients, however, do not respond to these
      drugs. For them it is necessary to find new therapeutic strategies. Mood
      stabilizers are promising in this regard. In particular, topiramate seems to
      allow reduction of binge eating and weight in SSRI non-responder patients. 

PMID- 24930554
TI  - Neuropsychiatric adverse events of bupropion treatment: a brief update.
AB  - The clinical use of bupropion as an aid for smoking cessation has raised some
      concern in clinicians and public opinion. Clinical and post-marketing
      surveillance studies indicate a favourable side effect profile, but spontaneous
      reports of suspected adverse reactions to medical authorities indicate adverse
      neuropsychiatric events to be more frequent than previously thought. Except for
      the risk of seizures, adverse neuropsychiatric events have not been examined
      systematically. Insomnia has been reported quite frequently. In the placebo
      controlled trials, depression scores were unaffected by bupropion treatment.
      Suspected adverse events reported to medical authorities in the UK or Germany
      indicate depression to be the most common psychiatric disorder associated with
      bupropion treatment. Switch to mania or hypomania is very rare, as are psychosis
      or organic mental disorders. Suicide attempts associated with bupropion use have
      been reported as possible adverse events. This topic warrants further attention. 

PMID- 24930553
TI  - The Rivermead Behavioural Memory Test can predict social functioning among
      schizophrenic patients treated with clozapine.
AB  - OBJECTIVE The aim of this study was to find out whether clinical symptoms, such
      as positive and negative symptoms, or cognitive problems, such as impairment in
      memory, are predictive of social outcome among patients with schizophrenia and
      treated with clozapine in the long-term. METHODS Twelve subjects with a DSM-III-R
      diagnosis of schizophrenia treated with clozapine were recruited from an
      inpatient rehabilitation psychiatry unit. Subjects were assessed at baseline, and
      6, 12 and 24 months, using symptoms measures, the Social Behaviour Scale (SBS)
      and the Rivermead Behavioural Memory Test (RBMT), which tests episodic memory.
      Three multivariate stepwise regression models were created with SBS at 6, 12 and
      24 months score as dependent variable, and the other measures at baseline as
      independent variables. RESULTS The only significant contribution on social
      functioning in each model was made by the RBMT, which was therefore the only
      significant predictor of social functioning in all models. CONCLUSIONS The
      authors discuss the importance of episodic memory in the prediction of social
      functioning. 

PMID- 24930555
TI  - Efficacy and safety of milnacipran in the treatment of generalized anxiety
      disorder: an open study.
AB  - OBJECTIVE The aim of this open study was to assess the efficacy and safety of the
      serotonin-noradrenaline reuptake-inhibiting antidepressant, milnacipran, for the
      treatment of generalised anxiety disorder. METHODS Twelve patients, treated with
      milnacipran at doses from 30 to 150 mg/day for 8 weeks, were evaluated at
      baseline and after 1, 2, 3, 4, 6 and 8 weeks of treatment using the Hamilton
      Anxiety Rating (HAM-A) scale and a self-rating visual analogue scale. RESULTS Two
      patients dropped out early in the trial because of adverse effects. The 10
      patients who completed the trial showed a marked improvement in anxiety symptoms
      with HAM-A scores being reduced from 21.6+/-6.5 (mean+/-SD) to 1.5+/-1.8 after 8
      weeks. All of the patients who completed the 8 weeks of treatment had a reduction
      of at least 70% in their HAM-A score. Adverse effects, principally nausea, were
      mild and occurred early in the study, regressing as the study progressed.
      CONCLUSION These results suggest that milnacipran is effective and well tolerated
      in patients suffering from generalised anxiety disorder. A full-scale double
      blind placebo trial is clearly warranted. 

PMID- 24930556
TI  - Occurrence of delirium after a short-term intake of olanzapine.
AB  - Olanzapine is an atypical antipsychotic drug, which is claimed to have fewer side
      effects than conventional antipsychotics. We report three cases where patients
      developed a classic delirium within a few days after first intake of olanzapine.
      The symptoms fulfilled all criteria of DSM-IV for delirium, and rapidly
      diminished after discontinuation of olanzapine. Additional reasons for the
      development of the delirias are possible, but less likely. Special awareness and
      future research of this phenomenon is highly indicated because of the common use
      of this drug. 

PMID- 24930557
TI  - Paroxetine augmentation to tianeptine treatment causes exacerbation of depressive
      symptoms: presentation of two cases.
AB  - We present two cases whose depressive symptoms partially remitted with tianeptine
      treatment but exacerbated after paroxetine augmentation to tianeptine. Although
      tianeptine has structural similarities with tricyclic antidepressants, unlike
      tricyclic agents or selective serotonin- reuptake inhibitors(SSRIs), it enhances
      5-HT reuptake in brain, leading to decreased availability of the transmitter in
      the synaptic cleft. Thus, efficacy of tianeptine as an antidepressant agent
      caused a challenge to the concept of serotonergic deficit theory in depression.
      Both paroxetine and tianeptine are found equivalently effective in treatment of
      major depression, but no data are available for combined use of these two agents.

PMID- 24930558
TI  - Occult benzodiazepine dependence.
AB  - Illicit street heroin is often adulterated with other substances, which may
      expose the unknowing user to additional adverse risks. This case study describes
      an intravenous heroin user with a history of epileptic seizures, who presented
      with unexpected benzodiazepine withdrawal symptoms. It highlights the importance
      of a thorough drug history with corroborative urine drug testing. 

PMID- 24930561
TI  - Fe(II) uptake on natural montmorillonites. II. Surface complexation modeling.
AB  - Fe(II) sorption edges and isotherms have been measured on low structural Fe
      content montmorillonite (STx) and high structural Fe-content montmorillonite
      (SWy) under anoxic (O2 < 0.1 ppm) and strongly reducing conditions (Eh = -0.64
      V). Under anoxic conditions Fe(II) sorption on SWy was significantly higher than
      on STx, whereas the sorption under reducing conditions was essentially the same.
      The uptake behavior of Fe(II) on STx under all redox conditions (Eh = +0.28 to 
      0.64 V) and SWy under reducing conditions (Eh = -0.64 V) was consistent with
      previous measurements made on other divalent transition metals. All of the
      sorption data could be modeled with the two-site protolysis nonelectrostatic
      surface complexation and cation exchange (2SPNE SC/CE) sorption model including
      an additional surface complexation reaction for Fe(II) which involved the surface
      oxidation of ferrous iron surface complexes (=S(S,W)OFe(+)) to ferric iron
      surface complexes (=S(S,W)OFe(2+)) on both the strong and weak sites. The
      electron acceptor sites on the montmorillonite are postulated to be the
      structural Fe(III). 

PMID- 24930560
TI  - Detection of anti-CADM-140/MDA5 antibodies in a patient with classic
      dermatomyositis developing rapidly progressive interstitial lung disease.

PMID- 24930562
TI  - A novel chromo- and fluorogenic dual sensor for Mg(2+) and Zn(2+) with cell
      imaging possibilities and DFT studies.
AB  - A diformyl-p-cresol (DFC)-8-aminoquinoline based dual signaling probe was found
      to exhibit colorimetric and fluorogenic properties on selective binding towards
      Mg(2+) and Zn(2+). Turn-on fluorescent enhancements (FE) as high as 40 fold and
      53 fold in 9 : 1 MeCN/water (v/v) at pH 7.2 in HEPES buffer for Mg(2+) and
      Zn(2+), respectively, were observed. The binding constants determined from the
      fluorescence titration data are: K = (1.52 +/- 0.21) * 10(5) M(-1) and (9.34 +/-
      4.0) * 10(3) M(-2) at n = 1 and 0.5, for Mg(2+) and Zn(2+), respectively. The L :
      M binding ratios were also determined by Job's method, which support the above
      findings. This is further substantiated by HRMS analysis. Due to solubility in
      mixed organo-aqueous solvents as well as cell permeability it could be used for
      the in vitro/in vivo cell imaging of Mg(2+) and Zn(2+) ions with no or negligible
      cytotoxicity. This probe could be made selective towards Mg(2+) over Zn(2+) in
      the presence of TPEN, both under intra- and extracellular conditions and is
      superior to other Mg(2+) probes which suffer from selectivity of Mg(2+) over
      Ca(2+) or Zn(2+). Furthermore the dissociation constant (Kd = 6.60 MUM) of the
      Mg(2+)-() complex is far lower than the so far reported Mg(2+) probes which fall
      in the mM range. 

PMID- 24930563
TI  - Infection and rejection risk after cardiac transplantation with induction vs. no
      induction: a multi-institutional study.
AB  - Data from Cardiac Transplant Research Database (CTRD) were analyzed from 1999 to
      2006 to examine the effects of different induction strategies at the time of
      cardiac transplantation. A total of 2090 primary heart transplants were
      categorized by induction with interleukin-2 receptor blocker (IL-2RB),
      antithymocyte globulin (ATG), or no induction (NI). Probabilities for rejection
      and infection were estimated with parametric time-related models. Using these
      models, hazard was calculated for two theoretical patient profiles, one at lower
      risk for rejection and higher risk of infection (Profile 1) and higher risk for
      rejection and lower risk of infection (Profile 2). Of the 2090 transplants, 49.8%
      (1095) did not receive induction, 27.3% (599) received IL-2RB, and 18.0% (396)
      received ATG. Profile 1 patients had lower hazard for rejection with IL-2RB
      compared to ATG and NI (p < 0.01), but at the cost of increased risk of infection
      (5.0 vs. 1.8 vs. 1.6, respectively, at four wk, p < 0.01). Profile 2 patients
      experienced a fivefold decreased hazard for rejection when treated with IL-2RB
      compared with ATG and NI (p < 0.01). In patients at high risk of infection, IL
      2RB reduced risk of rejection but at the expense of increased hazard for
      infection. 

PMID- 24930564
TI  - High revision rate following artificial urethral sphincter implantation.
AB  - OBJECTIVE: In severe cases of stress urinary incontinence (SUI), with sphincter
      dysfunction, the artificial urinary sphincter AMS 800TM may be the last solution.
      The purpose of this study was to evaluate the outcome of surgical intervention
      for SUI with the AMS 800 in patients who were treated at Sahlgrenska University
      Hospital, Gothenburg. The primary aim of the study was to determine the
      complications related to the operation. MATERIAL AND METHODS: A retrospective
      follow-up was done by reviewing medical records. The material comprised 97 men,
      who underwent their first AMS 800 implantation between May 1997 and June 2010 at
      Sahlgrenska University Hospital. RESULTS: The revision rate was 28%, including an
      infection rate of 3% and an erosion rate of 7%. The mean follow-up for revised
      patients was 3 years. The median time until revision was 1 year. Seventy-five per
      cent of all patients were satisfied with the operation at 6 months' follow-up.
      Radical prostatectomy was the reason behind incontinence in 84% of patients in
      this series. CONCLUSION: The results clearly demonstrate a need for revision
      procedures in a considerable proportion of patients implanted with an AMS 800
      device. Patient satisfaction was high, but although this operation has extremely
      low mortality it has its complications and the system will need to be replaced in
      time.

PMID- 24930565
TI  - Hand-assisted partial nephrectomy with early arterial clamp removal: Impact of
      the learning curve.
AB  - OBJECTIVE: The aims of this study were to present the results of hand-assisted
      laparoscopic partial nephrectomy according to the margin, ischaemia and
      complications system; to assess the role of the learning curve; and to compare
      this approach with other approaches. MATERIAL AND METHODS: Data from 60
      consecutive patients were obtained from a prospectively maintained database. The
      patients were divided into three cohorts (1, 2 and 3), with 20 patients each,
      according to their surgery dates. RESULTS: The overall margin, ischaemia and
      complications rate was 90%. The warm ischaemia time was 9.5 min in cohort 1,
      decreasing to 5 min in cohort 3 (p < 0.0001). The Padua score (p = 0.0287) and
      tumour size (p = 0.0003) were significantly increased in cohort 3, but loss of
      kidney function decreased significantly to 3.5% in this cohort. Loss of kidney
      function of less than 5% was reported for eight (40%), nine (45%) and 14 (70%)
      patients in cohorts 1, 2 and 3, respectively (p = 0.0185). CONCLUSIONS: Hand
      assisted laparoscopic partial nephrectomy with early removal of arterial clamps
      is safe and easy to learn. An expert laparoscopic surgeon can perform hand
      assisted laparoscopic partial nephrectomy for complex tumours with a relatively
      high success rate according to the margin, ischaemia and complications system.
      Warm ischaemia time could be obtained within 5 min after 40 procedures.

PMID- 24930566
TI  - In vitro approaches to pharmacological screening in the field of atopic
      dermatitis.
AB  - In vitro models are valuable for evaluating potential active ingredients and
      other molecules used in medications for atopic dermatitis (AD). However, finding
      appropriate in vitro models can be problematic. Our strategy was to set up
      different in vitro models that would mimic the pathomechanisms of AD. We describe
      five such models - the AD keratinocyte model, the AD reconstructed human
      epidermis model, the adaptive immunity model, the innate immunity model and the
      pruritus model - which we have used to evaluate a new ingredient for emollients
      derived from a biological extract. The models chosen provide useful data for the
      pharmacological characterization of active ingredients in adjunctive treatments
      for AD.

PMID- 24930567
TI  - Psychodermatological aspects of atopic dermatitis.
AB  - Psychodermatology is an evolving area of science that focuses on the interaction
      between the mind, skin and body. It is known that various neuroendocrine
      mediators - including adrenocorticotropin, beta-endorphin, catecholamines and
      cortisol - are produced in response to stress. The resulting increase in
      endogenous glucocorticoids can disrupt the skin's barrier function, leaving it
      vulnerable to inflammatory disorders like atopic dermatitis (AD). In turn, AD is
      associated with high levels of stigmatization, social withdrawal, anxiety and
      depression among patients and their carers. It is well known that the stress
      caused by AD can make the symptoms of the disease worse. Therefore, the goal of
      psychodermatological treatment is not only to improve the condition of the skin,
      but also to teach patients/carers how to cope with the disease. This requires a
      multifaceted approach, and time and patience, to ascertain the needs of
      individual patients. A multidisciplinary team that includes a dermatologist,
      psychiatrist and psychologist will be necessary to deliver high-quality, tailored
      care to patients.

PMID- 24930569
TI  - Initial phases in the development of a European Organisation for Research and
      Treatment of Cancer communication-specific module.

PMID- 24930568
TI  - Resource implications of running a sacral neuromodulation service: a 10-year
      experience.
AB  - AIM: In this study we reviewed our 10-year experience of the medium- to long-term
      success of sacral nerve stimulation (SNS) for faecal incontinence, with
      particular reference to the resource implications of running such a service.
      METHOD: All patients treated with permanent SNS implants for faecal incontinence
      from 2001 to 2012 were identified from a prospective database. The patients
      underwent follow up at 3 and 6 months, with annual review thereafter. They were
      divided into four groups: group 1, patients optimized after two reviews; group 2,
      patients optimized after further review; group 3, patients who failed to reach a
      satisfactory state; and group 4, patients who had a good initial result with
      subsequent failure. RESULTS: Eighty-five patients underwent permanent SNS with a
      median follow up of 24 (range: 3-108) months. Group 1 included 30 (35%) patients;
      group 2 included 27 (32%) patients [median of two (range: 2-6) additional
      visits]; group 3 included 18 (21%) patients [median of six (range: 3-10)
      additional visits]; and group 4 included 10 (12%) patients [median interval to
      failure was 54 (range: 24-84) months]. Twenty-seven per cent of our patients had
      an unsatisfactory outcome and the cost of follow up for these patients was
      L36,854 (48.7% of the total follow-up costs). CONCLUSION: The study highlights
      the significant resource implications of running an SNS service with a large
      proportion of patients requiring prolonged review, with more than one-quarter
      having an unsatisfactory outcome at a substantial cost.

PMID- 24930570
TI  - Trap and track: designing self-reporting porous Si photonic crystals for rapid
      bacteria detection.
AB  - The task of rapid detection and identification of bacteria remains a major
      challenge in both medicine and industry. This work introduces a new concept for
      the design of self-reporting optical structures that can detect and quantify
      bacteria in real-time. The sensor is based on a two-dimensional periodic
      structure of porous Si photonic crystals in which the pore size is adjusted to
      fit the target bacteria cells (Escherichia coli). Spontaneous bacteria capture
      within the pores induces measurable changes in the zero-order reflectivity
      spectrum collected from the periodic structure. Confocal laser microscopy and
      electron microscopy confirm that the Escherichia coli cells are individually
      imprisoned within the porous array. A simple model is suggested to correlate the
      optical readout and the bacteria concentration and its predictions are found to
      be in good agreement with experimental results. In addition, we demonstrate that
      sensing scheme can be easily modified to potentially allow monitoring of
      concentration, growth and physiological state of bacteria cells. This generic
      platform can be tailored to target different microorganisms by tuning the array
      periodicity and its surface chemistry for rapid and label-free detection outside
      the laboratory environment. 

PMID- 24930571
TI  - Investigation of the protective effects of proanthocyanidin and vitamin E against
      the toxic effect caused by formaldehyde on the liver tissue.
AB  - We aimed to investigate of protective role of proanthocyanidin (PA) and vitamin E
      (vit E) against to toxic effect of formaldehyde (FA). Twenty-eight Wistar albino
      rats were divided into four groups: control group, rats treated with FA
      intraperitoneal (i.p.) (10 mg/kg), FA + vit E intragastric (i.g.) (30 mg/kg), and
      FA + PA i.g. (100 mg/kg). We assayed superoxide dismutase (SOD), glutathione
      peroxidase (Gpx), myeloperoxidase (MPO) activity and levels of malondialdehyde
      (MDA) and total sialic acid (TSA) in liver. Liver tissue was taken in order to
      morphological analysis and hepatocytes apoptosis using terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) assay immunostaining. SOD decreased in
      FA and increased in FA + vit E and FA + PA (p < 0.05). Gpx didn't change in FA
      and increased in FA + PA (p < 0.05). No significant variation between the groups
      was found in MPO activity. MDA increased only in FA and decreased in FA + vit E
      and FA+PA (p < 0.05). TSA didn't alter in FA and FA + vit E but decreased in FA +
      PA (p < 0.05). Degeneration in hepatocytes and endothelial cells, cytoplasm
      losses, vacuolization, picnotic nuclei, and mononuclear cell infiltration were
      identified in FA. Degeneration in chromatin material, membrane damage in
      mitochondria and losses in mitochondrial cristae in hepatocytes were observed in
      FA. We found that partially recovery in liver as a result of FA + vit E and FA +
      PA. We have concluded that long term use should be investigated for complete
      explanation of PA's protective effects on FA toxicity.

PMID- 24930572
TI  - Catalytic formation of monosaccharides: from the formose reaction towards
      selective synthesis.
AB  - The formose reaction (FR) has been long the focus of intensive investigations as
      a simple method for synthesis of complex biologically important monosaccharides
      and other sugar-like molecules from the simplest organic substrate-formaldehyde.
      The fundamental importance of the FR is predominantly connected with the
      ascertainment of plausible scenarios of chemical evolution which could have
      occurred on the prebiotic Earth to produce the very first molecules of
      carbohydrates, amino- and nucleic acids, as well as other vitally important
      substances. The practical importance of studies on the FR is the elaboration of
      catalytic methods for the synthesis of rare and non-natural monosaccharides and
      polyols. This Minireview considers the FR from the point of view of chemists
      working in the field of catalysis with emphasis on the mechanisms of numerous
      parallel and consequent catalytic transformations that take place during the FR.
      Based on its kinetics, the FR may be considered as a non-radical chain process
      with degenerate branching. The Minireview also considers different approaches to
      the control of selectivity of carbohydrate synthesis from formaldehyde and lower
      monosaccharides. 

PMID- 24930573
TI  - Effect of surface wettability properties on the electrical properties of printed
      carbon nanotube thin-film transistors on SiO2/Si substrates.
AB  - The precise placement and efficient deposition of semiconducting single-walled
      carbon nanotubes (sc-SWCNTs) on substrates are challenges for achieving printed
      high-performance SWCNT thin-film transistors (TFTs) with independent gates. It
      was found that the wettability of the substrate played a key role in the
      electrical properties of TFTs for sc-SWCNTs sorted by poly[(9,9-dioctylfluorene
      2,7-diyl)-co-(1,4-benzo-2,1,3-thiadiazole)] (PFO-BT). In the present work we
      report a simple and scalable method which can rapidly and selectively deposit a
      high concentration of sc-SWCNTs in TFT channels by aerosol-jet-printing. The
      method is based on oxygen plasma treatment of substrates, which tunes the surface
      wettability. TFTs printed on the treated substrates demonstrated a low operation
      voltage, small hysteresis, high mobility up to 32.3 cm(2) V(-1) s(-1), and high
      on/off ratio up to 10(6) after only two printings. Their mobilities were 10 and
      30 times higher than those of TFTs fabricated on untreated and low-wettability
      substrates. The uniformity of printed TFTs was also greatly improved. Inverters
      were constructed by printed top-gate TFTs, and a maximum voltage gain of 17 at
      Vdd = 5 V was achieved. The mechanism of such improvements is that the PFO-BT
      functionalized sc-SWCNTs are preferably immobilized on the oxygen plasma treated
      substrates due to the strong hydrogen bonds between sc-SWCNTs and hydroxyl groups
      on the substrates. 

PMID- 24930575
TI  - A case of a limbal adult onset xanthogranuloma.

PMID- 24930574
TI  - Emerging roles of Notch signaling in liver disease.
AB  - This review critically discusses the most recent advances in the role of Notch
      signaling in liver development, homeostasis, and disease. It is now clear that
      the significance of Notch in determining mammalian cell fates and functions
      extends beyond development, and Notch is a major regular of organ homeostasis.
      Moreover, Notch signaling is reactivated upon injury and regulates the complex
      interactions between the distinct liver cell types involved in the repair
      process. Notch is also involved in the regulation of liver metabolism,
      inflammation, and cancer. The net effects of Notch signaling are highly variable
      and finely regulated at multiple levels, but also depend on the specific cellular
      context in which Notch is activated. Persistent activation of Notch signaling is
      associated with liver malignancies, such as hepatocellular carcinoma with stem
      cell features and intrahepatic cholangiocarcinoma. The complexity of the pathway
      provides several possible targets for agents able to inhibit Notch. However,
      further cell- and context-specific in-depth understanding of Notch signaling in
      liver homeostasis and disease will be essential to translate these concepts into
      clinical practice and be able to predict benefits and risks of evolving
      therapies.

PMID- 24930576
TI  - Overlap between autistic and schizotypal personality traits is not accounted for
      by anxiety and depression.
AB  - Autism spectrum and schizophrenia spectrum disorders are classified separately in
      the DSM-5, yet research indicates that these two disorders share overlapping
      features. The aim of the present study was to examine the overlap between
      autistic and schizotypal personality traits and whether anxiety and depression
      act as confounding variables in this relationship within a non-clinical
      population. One hundred and forty-four adults completed the Autism Spectrum
      Quotient and the Schizotypal Personality Questionnaire and the Depression Anxiety
      Stress Scales-21. A number of associations were seen between autistic and
      schizotypal personality traits. However, negative traits were the only
      schizotypal feature to uniquely predict global autistic traits, thus highlighting
      the importance of interpersonal qualities in the overlap of autistic and
      schizotypal characteristics. The inclusion of anxiety and depression did not
      alter relationships between autistic and schizotypal traits, indicating that
      anxiety and depression are not confounders of this relationship. These findings
      have important implications for the conceptualisation of both disorders. 

PMID- 24930578
TI  - Clustering of symptoms of mental disorder in the medium-term following conflict:
      an epidemiological study in Timor-Leste.
AB  - It is important to define subpopulations with mental health and psychosocial
      reactions in the medium-term following conflict to ensure that an appropriate
      array of services are provided to meet the diversity of needs. We conducted a
      latent class analysis (LCA) on epidemiological data drawn from an urban and rural
      sample of 1221 adults (581 men and 640 women, response 82%) in post-conflict
      Timor Leste 4 years after the cessation of violence. The prevalence of PTSD was
      4.9%; severe distress 4.8%; anger attacks 38.3%; and paranoid-like symptoms
      10.9%. The best fitting LCA yielded three classes comprising those with no or
      minimal symptoms (86%), a class with anger-paranoia (13%) and a comorbid mental
      disorder class (1.5%) characterized by PTSD (100%) and severe distress (98%). The
      comorbid mental disorder class had an over-representation of men, the unemployed,
      residents in the urban area and persons with the greatest exposure to human
      rights trauma, murder and health stress. The anger-paranoia class experienced
      moderate levels of trauma and had an over-representation of urban dwellers,
      women, and those with higher levels of education. The analysis assists in
      clarifying the populations with mental disorder and adverse psychosocial
      reactions in need of intervention in the medium-term following conflict. 

PMID- 24930577
TI  - Snake fearfulness is associated with sustained competitive biases to visual snake
      features: hypervigilance without avoidance.
AB  - The extent and time course of competition between a specific fear cue and task
      related stimuli in early human visual cortex was investigated using
      electrophysiology. Steady-state visual evoked potentials (ssVEPs) were evoked
      using random-dot kinematograms that consisted of rapidly flickering (8.57 Hz)
      dots moving randomly, superimposed upon emotional or neutral distractor pictures.
      Participants were asked to detect intervals of coherently moving dots, ignoring
      the distractor pictures that varied in hedonic content. Women reporting high or
      low levels of snake fear were recruited from a large sample of healthy college
      students, and snake pictures served as fear-relevant distractors. The time
      varying amplitude of the ssVEP evoked by the motion detection task showed
      significant reduction when viewing emotionally arousing, compared to neutral,
      distractors, replicating previous studies. For high-fear participants, snake
      distractors elicited a sustained attenuation of task evoked ssVEP amplitude,
      greater than the attenuation prompted by other unpleasant arousing content. These
      findings support a hypothesis that fear cues prompt sustained hypervigilance
      rather than perceptual avoidance.

PMID- 24930579
TI  - Differentiation between free and bound leptin in depressed patients.
AB  - The relationship between leptin and affective disorders is still unknown. We
      measured free and bound leptin in 13 drug naive subjects. Leptin did not
      significantly differ between patients and controls. As part of future studies, it
      also appears useful to distinguish between free and bound leptin. 

PMID- 24930581
TI  - A cross-national factor analytic comparison of three models of PANSS symptoms in
      schizophrenia.
AB  - The 30-item Positive and Negative Syndrome Scale (PANSS) is used worldwide in the
      assessment of symptom severity in schizophrenia. The present study uses
      confirmatory factor analysis (CFA) to compare three different factorial models
      and to evaluate the best-fitting representation of schizophrenia symptom
      structure on the PANSS across four samples of patients diagnosed with
      schizophrenia from the US (the CATIE schizophrenia trial), Sao Paulo, Brazil, and
      from Beijing and Changsha, China. We examine the goodness of fit of several
      previously proposed models. The traditional trifactorial model for the PANSS and
      two five-factor models were evaluated using absolute and incremental indices.
      Single group CFA found that the five-factor model proposed by NIMH researchers
      based on an extensive literature review demonstrates the best fit in each of the
      four samples. This model used 20 of the 30 PANSS items grouped into five factors:
      positive, negative, disorganized, excited, and depressed symptoms. Subgroups
      defined by age, gender, nationality, hospitalization status, and severity of
      illness also did not differ in overall symptom structure as assessed by several
      standard indices. Our findings suggest that the five factor NIMH model showed the
      best representation among all four samples from different countries and
      potentially contrasting cultures. 

PMID- 24930580
TI  - Pharmacogenetics of adverse events in schizophrenia treatment: comparison study
      of ziprasidone, olanzapine and perazine.
AB  - The primary aim of the present study was to assess the possible associations
      between dopaminergic, serotonergic, and glutamatergic system-related genes and
      adverse events after antipsychotic treatment in paranoid schizophrenia patients.
      The second aim of the study was to compare the intensity of these symptoms
      between atypical (ziprasidone and olanzapine) and typical (perazine)
      antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from
      paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT,
      MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with
      perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of
      side effects (changes in body weights and extrapyramidal symptoms (EPS)) was
      measured at baseline and after 12 weeks of antipsychotic treatment. After 3
      months of therapy, the weight increase was the greatest in the group treated with
      olanzapine and the least in the group treated with ziprasidone. None of the
      examined gene polymorphisms was associated with the body weight changes. Perazine
      treatment was associated with the significantly highest intensity of EPS. None of
      the examined polymorphisms was associated with the changes in extrapyramidal
      adverse events after antipsychotic treatment. The selected polymorphisms are not
      primarily involved in changes in body weights and EPS related to antipsychotic
      treatment in paranoid schizophrenia patients. 

PMID- 24930582
TI  - Assessing blinding in trials of psychiatric disorders: a meta-analysis based on
      blinding index.
AB  - The assessment of blinding in RCTs is rarely performed. Currently most studies
      that do report data on evaluation of blinding merely report percentages of
      correct guessing, not taking into account correct guessing by chance. Blinding
      assessment using the blinding index (BI) has never been performed in a systematic
      review on studies of major psychiatric disorders. This study is a systematic
      review of psychiatric randomized control trials using the BI as a chance
      corrected measurement of blinding, a tool to analyze and understand the patterns
      of blinding across studies of major psychiatric disorders with available data. Of
      2467 psychiatric RCTs from 2000 to 2010, 66 reported on blinding and 40 studies
      were found to have enough information on evaluation of blinding to be analyzed
      using the BI. The experimental treatment groups had an average BI value of 0.14
      and the control groups had an average BI value of 0.00. The most common BI
      scenario was random-random, indicating ideal blinding. A positive correlation
      between effect size and more correct guesses was also found. Overall, based on BI
      values and the most common blinding scenario, the published articles on major
      psychiatric disorders from 2000 to 2010, which reported on blinding assessment
      for patients, were effectively blinded. 

PMID- 24930583
TI  - An incremental community detection method for social tagging systems using
      locality-sensitive hashing.
AB  - An increasing number of users interact, collaborate, and share information
      through social networks. Unprecedented growth in social networks is generating a
      significant amount of unstructured social data. From such data, distilling
      communities where users have common interests and tracking variations of users'
      interests over time are important research tracks in fields such as opinion
      mining, trend prediction, and personalized services. However, these tasks are
      extremely difficult considering the highly dynamic characteristics of the data.
      Existing community detection methods are time consuming, making it difficult to
      process data in real time. In this paper, dynamic unstructured data is modeled as
      a stream. Tag assignments stream clustering (TASC), an incremental scalable
      community detection method, is proposed based on locality-sensitive hashing. Both
      tags and latent interactions among users are incorporated in the method. In our
      experiments, the social dynamic behaviors of users are first analyzed. The
      proposed TASC method is then compared with state-of-the-art clustering methods
      such as StreamKmeans and incremental k-clique; results indicate that TASC can
      detect communities more efficiently and effectively. 

PMID- 24930584
TI  - Expression and localization of an ice nucleating protein from a soil bacterium,
      Pseudomonas borealis.
AB  - An ice nucleating protein (INP) coding region with 66% sequence identity to the
      INP of Pseudomonas syringae was previously cloned from P. borealis, a plant
      beneficial soil bacterium. Ice nucleating activity (INA) in the P. borealis DL7
      strain was highest after transfer of cultures to temperatures just above
      freezing. The corresponding INP coding sequence (inaPb or ina) was used to
      construct recombinant plasmids, with recombinant expression visualized using a
      green fluorescent protein marker (gfp encoding GFP). Although the P. borealis
      strain was originally isolated by ice-affinity, bacterial cultures with membrane
      associated INP-GFP did not adsorb to pre-formed ice. Employment of a shuttle
      vector allowed expression of ina-gfp in both Escherichia coli and Pseudomonas
      cells. At 27  degrees C, diffuse fluorescence appeared throughout the cells and
      was associated with low INA. However, after transfer of cultures to 4  degrees C,
      the protein localized to the poles coincident with high INA. Transformants with
      truncated INP sequences ligated to either gfp, or an antifreeze protein-gfp
      fusion showed that the repetitive ice-nucleation domain was not necessary for
      localization. Such localization is consistent with the flanking residues of the
      INP associating with a temperature-dependent secretion apparatus. A polar
      location would facilitate INP-INP interactions resulting in the formation of
      larger aggregates, serving to increase INA. Expression of INPs by P. borealis
      could function as an efficient atmospheric dispersal mechanism for these soil
      bacteria, which are less likely to use these proteins for nutrient procurement,
      as has been suggested for P. syringae.

PMID- 24930585
TI  - Does vitrification alter the methylation pattern of OCT4 promoter in rabbit late
      blastocyst?
AB  - Vitrification is replacing slow freezing as the most popular method for oocyte
      and embryo cryopreservation. However, very little information is available on
      alterations in epigenetic regulation. Previous studies reported post-implantation
      effects of vitrification on fetal development and gene expression. This study was
      conducted to determine if vitrification procedure induce alterations in OCT4
      promoter methylation profile which could determine the set point of fetal losses
      and transcriptomic alterations observed after implantation. Rabbit morulae were
      recovered at Day 3 of development and vitrified and transferred, or directly
      transfer, to recipient till Day 6. A conserved regulation region of OCT4 promoter
      was examined in control and vitrified embryos by bisulfite sequencing and
      quantitative PCR was used to measure the gene expression. No significant
      differences were observed in methylation levels or gene expression of OCT4. This
      work was the first approach in rabbit to the study of possible epigenetic
      alterations associated with vitrification procedure. 

PMID- 24930586
TI  - Mortality of patients with bullous pemphigoid in Korea.
AB  - BACKGROUND: The reported mortality rates and prognoses of bullous pemphigoid (BP)
      vary among different countries. However, the mortality rate of BP has not been
      investigated in Korea. OBJECTIVE: We sought to evaluate the mortality rate of
      Korean patients with BP in comparison to that of an age-matched general
      population in Korea, and to identify prognostic factors affecting overall
      survival. METHODS: We conducted a retrospective analysis of 168 patients
      diagnosed with BP between 1993 and 2013 at Gangnam Severance Hospital in Seoul,
      Korea. RESULTS: The 1-, 2-, and 5-year mortality rates of BP patients were 19.46%
      (95% confidence interval [CI], 13.83-27.00), 29.13% (95% CI, 21.91-38.08), and
      58.03% (95% CI, 47.04-69.45), respectively. The median age was 73 years (range, 6
      99 years). The standardized mortality ratio ranged from 2.43 (95% CI, 0.12-11.96)
      to 9.56 (95% CI, 2.43-26.02), depending on the age group. In multivariate
      analysis, old age at the time of diagnosis, stroke, diabetes, and delayed
      diagnosis were associated with increased mortality. LIMITATIONS: This study was
      conducted as a retrospective analysis and was based at a single institution.
      CONCLUSION: The mortality rate of patients with BP is significantly higher than
      that for the general population.

PMID- 24930588
TI  - Production of a sterol esterase from Ophiostoma piceae in batch and fed-batch
      bioprocesses using different Pichia pastoris phenotypes as cell factory.
AB  - The potential biotechnological applications for the Ophiostoma piceae sterol
      esterase (OPE) are conditioned to the availability of high enzyme amounts at low
      prices. This enzyme is a versatile biocatalyst with different biotechnological
      applications. In this work a systematic study on its heterologous production in
      different Pichia pastoris strains and operational strategies is presented. The
      best results were obtained using an AOX1 defective yeast strain in a fed-batch
      bioprocess using methanol as inducer substrate at a set point of 2.5 g L(-1) and
      sorbitol as cosubstrate by means of a preprogramed exponential feeding rate at a
      MU = 0.02 h(-1) , reaching 30 U mL(-1) of enzyme and a volumetric productivity of
      403.5 U L(-1) h(-1) . These values are twofold higher than those obtained with a
      Mut(+) phenotype using methanol a sole carbon source. OPE was the main protein
      secreted by the yeast, 55% for Mut(s) versus 25% for Mut(+.)

PMID- 24930587
TI  - Photodynamic therapy using chlorophyll-a in the treatment of acne vulgaris: a
      randomized, single-blind, split-face study.
AB  - BACKGROUND: Chlorophyll-a is a novel photosensitizer recently tested for the
      treatment of acne vulgaris. OBJECTIVE: We sought to evaluate the clinical
      efficacy and safety of chlorophyll-a photodynamic therapy used for acne
      treatment. METHODS: Subjects with acne on both sides of the face were included.
      Eight treatment sessions were performed over a 4-week duration. Half of the face
      was irradiated using a blue and red light-emitting diode after topical
      application of chlorophyll-lipoid complex. The other half underwent only light
      emitting diode phototherapy. The lesion counts and acne severity were assessed by
      a blinded examiner. Sebum secretion, safety, and histologic changes were also
      evaluated. RESULTS: In total, 24 subjects completed the study. Facial acne
      improved on both treated sides. On the chlorophyll-a photodynamic therapy-treated
      side, there were significant reductions in acne lesion counts, acne severity
      grades, and sebum levels compared with the side treated with light-emitting diode
      phototherapy alone. The side effects were tolerable in all the cases.
      LIMITATIONS: All the subjects were of Asian descent with darker skin types, which
      may limit the generalizability of the study. A chlorophyll-a arm alone is absent,
      as is a no-treatment arm. CONCLUSIONS: We suggest that chlorophyll-a photodynamic
      therapy for the treatment of acne vulgaris can be effective and safe with minimal
      side effects.

PMID- 24930589
TI  - Evaluation of an interactive web-based nursing course with streaming videos for
      medication administration skills.
AB  - PURPOSE: Nursing students should exhibit competence in nursing skills in order to
      provide safe and quality patient care. This study describes the design and
      students' response to an interactive web-based course using streaming video
      technology tailored to students' needs and the course objectives of the
      fundamentals of nursing skills clinical course. METHOD: A mixed-methodology
      design was used to describe the experience of 102 first-year undergraduate
      nursing students at a school of nursing in Jordan who were enrolled in the
      course. A virtual course with streaming videos was designed to demonstrate
      medication administration fundamental skills. The videos recorded the ideal lab
      demonstration of the skills, and real-world practice performed by registered
      nurses for patients in a hospital setting. After course completion, students
      completed a 30-item satisfaction questionnaire, 8 self-efficacy scales, and a 4
      item scale solicited their preferences of using the virtual course as a
      substitute or a replacement of the lab demonstration. Students' grades in the
      skill examination of the procedures were measured. Relationships between the main
      variables and predictors of satisfaction and self-efficacy were examined.
      RESULTS: Students were satisfied with the virtual course (3.9 +/- 0.56, out of a
      5-point scale) with a high-perceived overall self-efficacy (4.38 +/- 0.42, out of
      a 5-point scale). Data showed a significant correlation between student
      satisfaction, self-efficacy and achievement in the virtual course (r = 0.45-0.49,
      p < 0.01). The majority of students accessed the course from home and some faced
      technical difficulties. Significant predictors of satisfaction were ease of
      access the course and gender (B = 0.35, 0.25, CI = 0.12-0.57, 0.02-0.48
      respectively). The mean achievement score of students in the virtual class (7.5
      +/- 0.34) was significantly higher than that of a previous comparable cohort who
      was taught in the traditional method (6.0 +/- 0.23) (p < 0.05). Nearly 40% of the
      students believed that the virtual course is a sufficient replacement of the lab
      demonstration. CONCLUSIONS: The use of multimedia within an interactive online
      learning environment is a valuable teaching strategy that yields a high level of
      nursing student satisfaction, self-efficacy, and achievement. The creation and
      delivery of a virtual learning environment with streaming videos for clinical
      courses is a complex process that should be carefully designed to positively
      influence the learning experience. However, the learning benefits gained from
      such pedagogical approach are worth faculty, institution and students' efforts.

PMID- 24930590
TI  - Nanoassembly of probucol enables novel therapeutic efficacy in the suppression of
      lung metastasis of breast cancer.
AB  - Metastasis is one of the major obstacles hindering the success of cancer therapy.
      The directed nanoassembly of probucol results in the "DNP" system, which greatly
      improves the oral delivery of probucol and subsequently leads to a novel
      therapeutic efficacy of probucol in the suppression of lung metastasis of breast
      cancer. DNP is formed by employing the intermolecular hydrophobic interactions
      between probucol and polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl
      ether (also known as Triton X-100). After oral administration, the probucol
      concentration in the intestines is surprisingly about 200 times higher if it is
      applied as DNP rather than free probucol; it can be absorbed into intestinal
      enterocytes via clathrin-mediated endocytosis and transported into the systemic
      circulation through the lymphatic pathway. Moreover, the oral bioavailability of
      probucol is significantly higher-13.55 times higher-when applied as DNP in place
      of free probucol. The drug concentration in major organs is also significantly
      increased. The in vitro measurements show that the migration and invasion
      abilities of 4T1 cells are obviously inhibited by DNP. In particular, in an
      orthotopic metastatic breast cancer model, the notable suppression of lung
      metastasis from DNP is observed, but no effect is seen from the free-probucol
      suspension. As a result, the directed drug nanoassembly may open a new route for
      enhancing oral drug delivery and enable new therapeutic abilities for probucol
      against cancer metastasis. 

PMID- 24930591
TI  - Predicting faces and houses: category-specific visual action-effect prediction
      modulates late stages of sensory processing.
AB  - Our perception is fundamentally influenced by the way that we interact with the
      world. In particular, sensory events that are consistent with our planned actions
      are attenuated, both in terms of their phenomenology, and their neural response.
      Previous research in this domain has focused on simple-featured stimuli such as
      Gabor patches or sine wave tones, with attenuation normally occurring at early
      stages of sensory processing. In the current study we investigated this
      phenomenon using more ecologically valid stimuli that would likely involve higher
      level visual predictions. More specifically, we trained participants to associate
      different actions with the presentation of a face or a house. By recording ERPs
      we could utilise the modularity of face processing to determine the locus of
      sensory attenuation for these high-level stimuli, as well as identify content
      specific brain activity related to the prediction itself. In contrast to previous
      studies using low-level stimuli, we observed attenuation at later stages of
      visual processing, suggesting that higher-level predictions result in high-level
      prediction errors. We additionally observed significant differences over visual
      brain regions during action preparation dependent on whether participants were
      predicting to see a house or a face, perhaps reflecting preactivation of the
      predicted action effects. Furthermore, the degree to which participants showed
      evidence of preactivation, was correlated with the magnitude of their P2
      attenuation. Taken together, these findings provide new insight into motor
      prediction and its influence on perception. 

PMID- 24930592
TI  - Comparison on the fatty acid profiles of liver, subcutaneous fat and muscle from
      feedlot steers finished on diets supplemented with or without cinnamaldehyde or
      monensin.
AB  - BACKGROUND: Cinnamaldehyde (CIN) is the main active component of cinnamon
      (Cinnamomum cassia) oil and has been tested as alternative feed additive in
      cattle production. Little information was available on the effect of dietary CIN
      in comparison to monensin (MO) on beef fatty acid (FA) profile. This study
      analyzed FA profiles of liver, subcutaneous fat and pars costalis diaphragmatis
      (PCD) muscle obtained from steers (n = 70) finished on diets: control, a barley
      grain-silage feedlot diet; 330 mg/head.day MO; and 400, 800 or 1600 mg/head.day
      CIN treatments. RESULTS: Inclusion of MO or CIN did not affect total saturated,
      unsaturated, polyunsaturated FA and individual FA in the various tissues with
      exceptions that proportion of palmitic acid in PCD muscle was increased by 800
      mg/steer.day CIN (P < 0.05). There were positive correlations (P < 0.05) on
      oleic, linoleic, conjugated linoleic acid (CLA)-c9,t11 and 18:1-t10 between the
      subcutaneous fat and PCD muscle, and on alpha-linolenic acid, CLA-c9,t11 and 18:1
      t10 between PCD muscle and liver, whereas correlations on the FA between the
      subcutaneous fat and liver were not significant except for 18:1-t10 (P < 0.01).
      CONCLUSION: The results indicate that the supplementation of CIN and MO to
      feedlot diet has limited effect on beef FA profiles.

PMID- 24930593
TI  - Current understanding of HIV-1 and T-cell adaptive immunity: progress to date.
AB  - The cellular immune response to human immunodeficiency virus (HIV) has different
      components originating from both the adaptive and innate immune systems. HIV
      cleverly utilizes the host machinery to survive by its intricate nature of
      interaction with the host immune system. HIV evades the host immune system at
      innate ad adaptive, allows the pathogen to replicate and transmit from one host
      to another. Researchers have shown that HIV has multipronged effects especially
      on the adaptive immunity, with CD4(+) cells being the worst effect T-cell
      populations. Various analyses have revealed that, the exposure to HIV results in
      clonal expansion and excessive activation of the immune system. Also, an abnormal
      process of differentiation has been observed suggestive of an alteration and
      blocks in the maturation of various T-cell subsets. Additionally, HIV has shown
      to accelerate immunosenescence and exhaustion of the overtly activated T-cells.
      Apart from causing phenotypic changes, HIV has adverse effects on the functional
      aspect of the immune system, with evidences implicating it in the loss of the
      capacity of T-cells to secrete various antiviral cytokines and chemokines.
      However, there continues to be many aspects of the immune- pathogenesis of HIV
      that are still unknown and thus required further research in order to convert the
      malaise of HIV into a manageable epidemic. 

PMID- 24930594
TI  - Gelidium elegans, an edible red seaweed, and hesperidin inhibit lipid
      accumulation and production of reactive oxygen species and reactive nitrogen
      species in 3T3-L1 and RAW264.7 cells.
AB  - Gelidium elegans is an edible red alga native to the intertidal area of
      northeastern Asia. We investigated the effect of G. elegans extract and its main
      flavonoids, rutin and hesperidin, on lipid accumulation and the production of
      reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3-L1 and
      RAW264.7 cells. Our data show that G. elegans extract decreased lipid
      accumulation and ROS/RNS production in a dose-dependent manner. The extract also
      inhibited the mRNA expression of adipogenic transcription factors, such as
      peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding
      protein alpha, while enhancing the protein expression of the antioxidant enzymes
      superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase
      compared with controls. In addition, lipopolysaccharide-induced nitric oxide
      production was significantly reduced in G. elegans extract-treated RAW264.7
      cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation
      and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid
      accumulation and ROS production; rutin did not affect adipogenesis and ROS
      status. The antiadipogenic effect of hesperidin was evidenced by the
      downregulation of peroxisome proliferator-activated receptor gamma,
      CCAAT/enhancer-binding protein alpha, and fatty acid binding protein 4 gene
      expression. Collectively, our data suggest that G. elegans is a potential food
      source containing antiobesity and antioxidant constituents.

PMID- 24930595
TI  - Consuming calories and creating cavities: beverages NZ children associate with
      sport.
AB  - Sugar-sweetened beverages (SSBs) are widely available, discounted and promoted,
      and despite recommendations to the contrary, frequently consumed by children.
      They provide few nutritional benefits, and their consumption is implicated in a
      number of poor health outcomes. This study examined the nature of the beverages
      that sport-playing New Zealand (NZ) children associate with sport. It assessed
      how well the beverages aligned with nutrition guidelines and relevant
      regulations, and their likely impacts on health. Eighty-two children (38 girls
      and 44 boys) aged 10-12 years were purposively selected from netball, rugby and
      football clubs in low and high socioeconomic neighbourhoods, in Wellington, New
      Zealand (NZ). Children photographed beverages they associated with sport. The
      beverages were then purchased and analysed in accordance with NZ nutrition
      guidelines, and relevant content and labelling regulations, by: package and
      serving size; energy, sugar, sodium and caffeine content; pH; and advisory
      statements. The beverages the children associated with sport overwhelmingly had
      characteristics which do not support children in adhering to NZ nutrition
      guidelines. Implementing public health mechanisms, such as healthy food and
      beverage policies, widely promoting water as the beverage of choice in sport, and
      implementing healthy eating and drinking campaigns in sports clubs, would assist
      children who play organised sport to select beverages that are in keeping with
      children's nutrition guidelines. As part of a comprehensive public health
      approach they would also reduce the substantial, unnecessary and potentially
      harmful contribution sugar-sweetened beverages make to their diet. 

PMID- 24930596
TI  - Comparison of text messaging and paper-and-pencil for ecological momentary
      assessment of food craving and intake.
AB  - Electronic devices such as mobile phones are quickly becoming a popular way to
      gather participant reports of everyday thoughts, feelings, and behaviors,
      including food cravings and intake. Electronic devices offer a number of
      advantages over alternative methods such as paper-and-pencil (PNP) assessment
      including automated prompts, on-the-fly data transmission, and participant
      familiarity with and ownership of the devices. However, only a handful of studies
      have systematically compared compliance between electronic and PNP methods of
      ecological momentary assessment (EMA), and none have examined eating
      specifically. Existing comparisons generally find greater compliance for
      electronic devices than PNP, but there is variability in the results across
      studies that may be accounted for by differences across research domains. Here,
      we compared the two EMA methods in an unexamined domain - eating - in terms of
      response rate and response latency, and their sensitivity to individual
      difference variables such as body mass index (BMI). Forty-four participants were
      randomly assigned to report on their food craving, food intake, and hunger four
      times each day for 2 weeks using either a PNP diary (N = 19) or text messaging
      (TXT; N = 25). Response rates were higher for TXT than PNP (96% vs. 70%) and
      latencies were faster (29 min vs. 79 min), and response rate and latency were
      less influenced by BMI in the TXT condition than in the PNP condition. These
      results support the feasibility of using text messaging for EMA in the eating
      domain, and more broadly highlight the ways that research domain-specific
      considerations (e.g., the importance of response latency in measuring short-lived
      food craving) interact with assessment modality during EMA. 

PMID- 24930597
TI  - Elevated objectively measured but not self-reported energy intake predicts future
      weight gain in adolescents.
AB  - BACKGROUND: Although obesity putatively occurs when individuals consume more
      calories than needed for metabolic needs, numerous risk factor studies have not
      observed significant positive relations between reported caloric intake and
      future weight gain, potentially because reported caloric intake is inaccurate.
      OBJECTIVE: The present study tested the hypothesis that objectively measured
      habitual energy intake, estimated with doubly labeled water, would show a
      stronger positive relation to future weight gain than self-reported caloric
      intake based on a widely used food frequency measure. DESIGN: Two hundred and
      fifty-three adolescents completed a doubly labeled water (DLW) assessment of
      energy intake (EI), a food frequency measure, and a resting metabolic rate (RMR)
      assessment at baseline, and had their body mass index (BMI) measured at baseline
      and at 1- and 2-year follow-ups. RESULTS: Controlling for baseline RMR, elevated
      objectively measured EI, but not self-reported habitual caloric intake, predicted
      increases in BMI over a 2-year follow-up. On average, participants under-reported
      caloric intake by 35%. CONCLUSIONS: RESULTS provide support for the thesis that
      self-reported caloric intake has not predicted future weight gain because it is
      less accurate than objectively measured habitual caloric intake, suggesting that
      food frequency measures can lead to misleading findings. However, even
      objectively measured caloric intake showed only a moderate relation to future
      weight gain, implying that habitual caloric intake fluctuates over time and that
      it may be necessary to conduct serial assessments of habitual intake to better
      reflect the time-varying effects of caloric intake on weight gain.

PMID- 24930598
TI  - Effects of children's self-regulation of eating on parental feeding practices and
      child weight.
AB  - The purpose of this study was to determine whether self-regulation of eating in
      minority preschool-aged children mediates the relationship between parent feeding
      practices and child weight. Participants were 299 low-income African American and
      Hispanic parents and their preschool-aged children who participated in Head
      Start. Parents completed questionnaires about controlling feeding practices
      (pressure to eat, restriction) and children's appetitive characteristics
      (enjoyment of food, food responsiveness, satiety responsiveness). Path analyses
      were used to determine whether children's self-regulation of eating mediated the
      relationship between feeding practices and child weight. Greater satiety
      responsiveness in African American preschool-age children partially mediated the
      inverse association between pressure to eat and children's weight, B (SE) = 
      0.073 (0.036), P < .05. Enjoyment of food and food responsiveness did not mediate
      the relationship between pressure to eat and weight in the African American
      sample, ps > .05, nor did appetitive characteristics mediate the relationship
      between restriction and child weight, ps > .05. Appetitive characteristics did
      not mediate the relationship between controlling feeding practices and child
      weight in the Hispanic sample, ps > .05. Implications include the need for
      culturally sensitive self-report measures and for researchers to account for the
      possible effects of racial/ethnic differences when designing interventions. 

PMID- 24930600
TI  - Epicardial placement of mesenchymal stromal cell-sheets for the treatment of
      ischemic cardiomyopathy; in vivo proof-of-concept study.
AB  - Transplantation of bone marrow mesenchymal stromal cells (MSCs) is an emerging
      treatment for heart failure. We have reported that epicardial placement of MSC
      sheets generated using temperature-responsive dishes markedly increases donor MSC
      survival and augments therapeutic effects in an acute myocardial infarction (MI)
      model, compared to intramyocardial (IM) injection. This study aims to expand this
      knowledge for the treatment of ischemic cardiomyopathy, which is likely to be
      more difficult to treat due to mature fibrosis and chronically stressed
      myocardium. Four weeks after MI, rats underwent either epicardial MSC-sheet
      placement, IM MSC injection, or sham treatment. At day 28 after treatment, the
      cell-sheet group showed augmented cardiac function improvement, which was
      associated with over 11-fold increased donor cell survival at both days 3 and 28
      compared to IM injection. Moreover, the cell-sheet group showed improved
      myocardial repair, in conjunction with amplified upregulation of a group of
      reparative factors. Furthermore, by comparing with our own previous data, this
      study highlighted similar dynamics and behavior of epicardially placed MSCs in
      acute and chronic stages after MI, while the acute-phase myocardium may be more
      responsive to the stimuli from donor MSCs. These proof-of-concept data encourage
      further development of the MSC-sheet therapy for ischemic cardiomyopathy toward
      clinical application. 

PMID- 24930599
TI  - Translating the immunogenicity of prime-boost immunization with ChAd63 and MVA ME
      TRAP from malaria naive to malaria-endemic populations.
AB  - To induce a deployable level of efficacy, a successful malaria vaccine would
      likely benefit from both potent cellular and humoral immunity. These requirements
      are met by a heterologous prime-boost immunization strategy employing a
      chimpanzee adenovirus vector followed by modified vaccinia Ankara (MVA), both
      encoding the pre-erythrocytic malaria antigen ME-thrombospondin-related adhesive
      protein (TRAP), with high immunogenicity and significant efficacy in UK adults.
      We undertook two phase 1b open-label studies in adults in Kenya and The Gambia in
      areas of similar seasonal malaria transmission dynamics and have previously
      reported safety and basic immunogenicity data. We now report flow cytometry and
      additional interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) data
      characterizing pre-existing and induced cellular immunity as well as anti-TRAP
      IgG responses. T-cell responses induced by vaccination averaged 1,254 spot
      forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) across
      both trials and flow cytometry revealed cytokine production from both CD4(+) and
      CD8(+) T cells with the frequency of CD8(+) IFN-gamma-secreting monofunctional T
      cells (previously shown to associate with vaccine efficacy) particularly high in
      Kenyan adults. Immunization with ChAd63 and MVA ME-TRAP induced strong cellular
      and humoral immune responses in adults living in two malaria-endemic regions of
      Africa. This prime-boost approach targeting the pre-erythrocytic stage of the
      malaria life-cycle is now being assessed for efficacy in a target population. 

PMID- 24930601
TI  - Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse
      model of SCA7.
AB  - Spinocerebellar ataxia type 7 (SCA7) is a late-onset neurodegenerative disease
      characterized by ataxia and vision loss with no effective treatments in the
      clinic. The most striking feature is the degeneration of Purkinje neurons of the
      cerebellum caused by the presence of polyglutamine-expanded ataxin-7. Ataxin-7 is
      part of a transcriptional complex, and, in the setting of mutant ataxin-7, there
      is misregulation of target genes. Here, we designed RNAi sequences to reduce the
      expression of both wildtype and mutant ataxin-7 to test if reducing ataxin-7 in
      Purkinje cells is both tolerated and beneficial in an animal model of SCA7. We
      observed sustained reduction of both wildtype and mutant ataxin-7 as well as a
      significant improvement of ataxia phenotypes. Furthermore, we observed a
      reduction in cerebellar molecular layer thinning and nuclear inclusions, a
      hallmark of SCA7. In addition, we observed recovery of cerebellar transcripts
      whose expression is disrupted in the presence of mutant ataxin-7. These data
      demonstrate that reduction of both wildtype and mutant ataxin-7 by RNAi is well
      tolerated, and contrary to what may be expected from reducing a component of the
      Spt-Taf9-Gcn5 acetyltransferase complex, is efficacious in the SCA7 mouse. 

PMID- 24930603
TI  - The role of cell proteins in dengue virus infection.
AB  - Despite 70 years of study, dengue disease continues to be a global health burden.
      Treatment is only supportive based on presenting symptoms. To date, there is no
      licensed prophylactic vaccine and no specific antiviral drugs available. The
      pathogenesis mechanisms during dengue virus infections remain poorly understood,
      and the complete picture on risk factors for developing severe clinical illness
      is still unknown. Viruses as obligate intracellular parasites depend on the host
      cell machinery for replication. As a result of a co-evolution process for million
      years, viruses have developed sophisticated strategies to hijack and use cellular
      factors for entry, replication and propagation, alternate host transmission and
      to combat host cell defenses. This review focuses on recent reports about
      cellular proteins involved along the dengue virus replication cycle, in prime
      cellular targets during the infection of both humans and mosquito hosts and also
      on the proteomics and other approaches that are being used to reveal the entire
      orchestration and most significant processes altered during infection.
      Identification of the key host cell factors involve in these processes will
      provide a better understanding of how viruses replicate and cause disease, and
      how to develop more effective therapeutic interventions. BIOLOGICAL SIGNIFICANCE:
      Dengue disease is as a global health problem. The treatment is only supportive
      based on presenting symptoms. To date, there is no licensed prophylactic vaccine
      and no specific antiviral drugs available. The study of the interactions between
      virus and host cell proteins will provide a better understanding of how viruses
      replicate and cause disease. Here, we focus on the current knowledge about the
      cellular proteins involved during DENV infection in different target cells in the
      two hosts, mosquito and human.

PMID- 24930602
TI  - Serum-stabilized naked caspase-3 siRNA protects autotransplant kidneys in a
      porcine model.
AB  - The naked small interfering RNA (siRNA) of caspase-3, a key player in ischemia
      reperfusion injury, was effective in cold preserved and hemoreperfused kidneys,
      but not autotransplanted kidneys in our porcine models. Here, chemically modified
      serum stabilized caspase-3 siRNAs were further evaluated. The left kidney was
      retrieved and infused by University of Wisconsin solution with/without 0.3 mg
      caspase-3 or negative siRNA into the renal artery for 24-hour cold storage (CS).
      After an intravenous injection of 0.9 mg siRNA and right-uninephrectomy, the left
      kidney was autotransplanted for 2 weeks. The effectiveness of caspase-3 siRNA was
      confirmed by caspase-3 knockdown in the post-CS and/or post-transplant kidneys
      with reduced apoptosis and inflammation, while the functional caspase-3 siRNA in
      vivo was proved by detected caspase-3 mRNA degradation intermediates. HMGB1
      protein was also decreased in the post-transplanted kidneys; correlated
      positively with renal IL-1beta mRNA, but negatively with serum IL-10 or IL-4. The
      minimal off-target effects of caspase-3 siRNA were seen with favorable systemic
      responses. More importantly, renal function, associated with active caspase-3,
      HMGB1, apoptosis, inflammation, and tubulointerstitial damage, was improved by
      caspase-3 siRNA. Taken together, the 2-week autotransplanted kidneys were
      protected when caspase-3 siRNA administrated locally and systemically, which
      provides important evidence for future clinical trials. 

PMID- 24930604
TI  - Intra- and interboar variability in flow cytometric sperm sex sorting.
AB  - To improve the efficiency of porcine sperm sex sorting using flow cytometry, the
      aims of the present study were to determine the relevance of inter- and intraboar
      variability in sperm sortability and to evaluate the significance of ejaculate
      semen characteristics in such variability. In addition, the variability among
      boars in the ability of sex-sorted spermatozoa to survive liquid storage at 15 
      degrees C to 17  degrees C was also evaluated. In total, 132 ejaculates collected
      from 67 boars of different breeds that were housed at an artificial insemination
      center were used in three experiments. X- and Y-chromosome-bearing sperm were
      simultaneously separated according to the Beltsville sperm-sorting technology
      using a high-speed flow cytometer. In the first experiment, interboar variability
      in the ability of the ejaculated spermatozoa to undergo the flow-based sex
      sorting procedure was observed; the ejaculates of nearly 15% of the boars (n =
      67) did not exhibit well-defined X- and Y-chromosome-bearing spermatozoa peaks in
      the histogram, and the ejaculate sperm concentration demonstrated good predictive
      value for explaining this variation, as indicated by the area under the receiver
      operating characteristics curve (0.88, P < 0.001). In the second experiment, a
      certain degree of intraboar variability was observed only in the boars that
      showed poor sperm sortability (measured according to the presence or not a well
      defined split together with sperm sortability parameters) in the first ejaculate
      (n = 3). In contrast, boars classified as having good sperm sortability in the
      first ejaculate (n = 5) maintained this condition in five ejaculates collected
      over the subsequent 5 months. In the third experiment, sex-sorted spermatozoa
      from boars with good sperm sortability (n = 5) remained viable and motile (above
      70% in all boars) after 48 hours of storage at 15  degrees C to 17  degrees C,
      which may facilitate the commercial application of sex-sorted spermatozoa in
      swine artificial insemination programs.

PMID- 24930605
TI  - Effects of vitrification for germinal vesicle and metaphase II oocytes on
      subsequent centromere cohesion and chromosome aneuploidy in mice.
AB  - The present study examined the effect of vitrification on oocyte aneuploidy and
      centromere cohesion. Firstly, germinal vesicle (GV) and in vitro matured oocytes
      (metaphase II, MII) were vitrified by open-pulled straw method. Secondly, thawed
      GV oocytes were matured in vitro to detect the aneuploidy rate and the sister
      inter-kinetochore (iKT) distance (in situ spreading and immunofluorescent
      staining). The results revealed that the sister iKT distance and the aneuploidy
      rate in eggs matured from vitrified-thawed GV oocytes were higher than that from
      in vivo matured, in vitro matured, and in vitro matured frozen oocytes (0.47 +/-
      0.03 vs. 0.33 +/- 0.01 vs. 0.33 +/- 0.02 vs. 0.34 +/- 0.01 MUm; P < 0.01 and
      22.9% vs. 6.5% vs. 5.8% vs. 11.8%; P < 0.05, respectively). Furthermore, the
      percentage of sister chromosome pairs whose sister iKT distances were higher than
      0.9 MUm in eggs matured from vitrified-thawed GV oocytes (8.7%) was higher than
      that from in vivo matured (1.6%), in vitro matured (1.6%), and in vitro matured
      frozen oocytes (2.3%) (P < 0.05). The sister iKT distance was associated with
      centromere cohesion. To investigate whether vitrification of GV oocytes
      deteriorated centromere cohesion by affecting cohesin complex formation, thawed
      and fresh GV oocytes were used to detect the cohesin subunits (SMC1beta, STAG3,
      SMC3, and REC8) mRNA expression (quantitative real-time polymerase chain
      reaction). The relative expression of three cohesin subunits (SMC1beta, STAG3,
      and SMC3) was significantly decreased in GV oocytes after vitrification. In
      conclusion, vitrification of GV oocytes may result in the subsequent
      deterioration of centromere cohesion and an increase in the aneuploidy rate. MII
      oocytes may be the ideal candidate to avoid aneuploidy for fertility
      cryopreservation.

PMID- 24930606
TI  - Cross-talk between free and bound spermatozoa to modulate initial sperm:egg
      ratios at the site of fertilization in the mammalian oviduct.
AB  - This essay proposes that highly localized communication between free and bound
      spermatozoa in the caudal portion of the oviduct acts to regulate the numbers
      detaching from the epithelium and progressing to the site of fertilization close
      to the time of ovulation. Low initial sperm:egg ratios are essential for
      monospermic fertilization. Liberation of surface macromolecules and metabolic
      prompting from activated spermatozoa, together with altered patterns of sperm
      movement and dynamic differences in intracellular Ca(2+) ion status between
      neighboring sperm cells, would influence the progressive release of spermatozoa
      from the reservoir in the oviduct isthmus. Different intensities of preovulatory
      epithelial binding, reflecting a range of states in the sperm surface membranes
      and associated proteins, would provide a further explanation for a
      chronologically staggered periovulatory detachment of spermatozoa. Intimate sperm
      sperm interactions within the confines of the oviduct isthmus offer a sensitive
      means of fine-tuning the vanguard of competent male gametes reaching the isthmo
      ampullary junction.

PMID- 24930607
TI  - Finding the ideal biomaterial for aortic valve repair with ex vivo porcine left
      heart simulator and finite element modeling.
AB  - OBJECTIVES: Aortic valve (AV) repair (AVr) has become an attractive alternative
      to AV replacement for the correction of aortic insufficiency; however, little
      clinical evidence exists in determining which biomaterial at AVr would be
      optimal. Cusp replacement in AVr has been associated with increased long-term AVr
      failure. We measured the hemodynamic and biomaterial properties using an ex vivo
      porcine AVr model with clinically relevant biomaterials and generated a finite
      element model to ascertain which materials would be best suited for valve repair.
      METHODS: Porcine aortic roots with intact AVs were placed in a left heart
      simulator mounted with a high-speed camera for baseline valve assessment. The
      noncoronary cusp was excised and replaced with autologous porcine pericardium,
      glutaraldehyde-fixed bovine pericardial patch (Synovis), extracelluar matrix
      scaffold (CorMatrix), or collagen-impregnated Dacron (Hemashield). The
      hemodynamic parameters were measured for a range of cardiac outputs (2.5-6.5
      L/min) after repair. The biomaterial properties and St Jude Medical pericardial
      patch were determined using pressurization experiments. Finite element models of
      the AV and root complex were constructed to determine the hemodynamic
      characteristics and leaflet stresses. RESULTS: The geometric orifice areas after
      repair were significantly reduced in the Hemashield (P<.05) and CorMatrix
      (P=.0001) groups. Left ventricular work increased with increasing cardiac output
      (P=.001) in unrepaired valves, as expected, and was similar among all biomaterial
      groups. Finite element modeling of the biomaterials displayed differences in the
      percentage of changes in total Von Mises stress for both replaced (noncoronary
      cusp) and nonreplaced left and right cusps with the St Jude Medical pericardial
      patch (+4%, +24%) and autologous porcine pericardium (+5, +26%), with a lower
      percentage of changes than for the bovine pericardial patch (+12%, +27%),
      Hemashield (+30%, +9%), and CorMatrix (+13%, +32%). CONCLUSIONS: The present
      study has shown that postrepair left ventricular work did not increase despite a
      decrease in geometric orifice areas in the Hemashield and CorMatrix groups. The
      autologous porcine pericardium and St Jude Medical pericardial patch had the
      closest profile to normal AVs; therefore, either biomaterial might be best
      suited. Finally, the increased stresses found in the bovine pericardial patch,
      Hemashield, and CorMatrix groups might, after prolonged tensile exposure, be
      associated with late repair failure.

PMID- 24930610
TI  - Retroesophageal total anomalous pulmonary venous connection in a neonate.

PMID- 24930609
TI  - A paired membrane umbrella double-lumen cannula ensures consistent cavopulmonary
      assistance in a Fontan sheep model.
AB  - OBJECTIVES: The Avalon Elite (Macquet, Rastatt, Germany) double-lumen cannula can
      provide effective cavopulmonary assistance in a Fontan (total cavopulmonary
      connection) sheep model, but it requires strict alignment. The objective was to
      fabricate and test a newly designed paired umbrella double-lumen cannula without
      alignment requirement. METHODS: The paired membrane umbrellas were designed on
      the double-lumen cannula to bracket infusion blood flow toward the pulmonary
      artery. Two umbrellas were attached, one 4 cm above and one 4 cm below the
      infusion opening. Umbrellas were temporarily wrapped and glued to the double
      lumen cannula body to facilitate insertion. A total cavopulmonary connection mock
      loop was used to test cavopulmonary assistance performance and reliability with
      double-lumen cannula rotation and displacement. The paired umbrella double-lumen
      cannula also was tested in a total cavopulmonary connection adult sheep model (n
      = 6). RESULTS: The bench test showed up to 4.5 L/min pumping flow and
      approximately 90% pumping flow efficiency at 360 degrees  rotation and 8-cm
      displacement of double-lumen cannula. The total cavopulmonary connection model
      with compromised hemodynamics was successfully created in all 6 sheep. The
      cavopulmonary assistance double-lumen cannula with paired umbrellas was smoothly
      inserted into the superior vena cava and extracardiac conduit in all sheep. At
      3.5 to 4.0 L/min pump flow, the systolic arterial blood pressure and central
      venous pressure returned to normal baseline and remained stable throughout the 90
      minute experiment, demonstrating effective cavopulmonary assistance support.
      Double-lumen cannula rotation and displacement did not affect performance.
      Autopsy revealed well-opened and positioned paired umbrellas, and double-lumen
      cannulas were easily removed from the right jugular vein. CONCLUSIONS: Our double
      lumen cannula with paired umbrellas is easy to insert and remove. The paired
      umbrellas eliminated the strict alignment requirement and ensured consistent
      cavopulmonary assistance performance.

PMID- 24930611
TI  - A quarter of a century of experience with aortic valve-sparing operations.
AB  - OBJECTIVE: To examine the late outcomes of aortic valve-sparing operations to
      treat patients with aortic root aneurysm with and without aortic insufficiency
      (AI) in a cohort of patients followed up prospectively since 1988. METHODS: A
      total of 371 consecutive patients had undergone aortic valve-sparing surgery
      (mean age, 47 +/- 15 years; 78% men) from 1988 through 2010. In addition to the
      aortic root aneurysm, 47% had moderate or severe AI, 35.5% had Marfan syndrome,
      12.1% had type A aortic dissection, 9.2% had bicuspid aortic valve, 8.4% had
      mitral insufficiency, 16.1% had aortic arch aneurysm, and 10.2% had coronary
      artery disease. Reimplantation of the aortic valve was used in 296 patients and
      remodeling of the aortic root in 75. Cusp repair by plication of the free margin
      along the nodule of Arantius was used in 36.6% of patients, and reinforcement of
      the free margin with a double layer of fine Gore-Tex suture in 24.2%. The
      patients were followed up prospectively with images of the aortic root for a
      median follow-up of 8.9 +/- 5.2 years. RESULTS: A total of 4 operative and 39
      late deaths occurred. Survival at 18 years was 76.8% +/- 4.31%, lower than that
      for the general population matched for age and gender. Age, type A aortic
      dissection, impaired ventricular function, and preoperative AI were associated
      with increased mortality on multivariable analysis. Reoperations on the aortic
      valve were performed in 8 patients for recurrent AI and in 2 for infective
      endocarditis. Freedom from reoperation on the aortic valve at 18 years was 94.8%
      +/- 2.0%. No predictors of the need for reoperation were found on multivariable
      analysis. Eighteen patients developed AI greater than mild. Freedom from AI
      greater than mild at 18 years was 78.0% +/- 4.8%. No predictors of recurrent AI
      were identified on multivariable analysis. CONCLUSIONS: Aortic valve-sparing
      operations continue to provide excellent clinical outcomes, although a slow but
      progressive deterioration of aortic valve function seems to occur during the
      first 2 decades of follow-up. Preoperative AI and cusp repair had no adverse
      effect on valve function.

PMID- 24930614
TI  - Selective use of cardiac computed tomography angiography: an alternative
      diagnostic modality before second-stage single ventricle palliation.
AB  - OBJECTIVES: To assess the accuracy and risk of substituting cardiac computed
      tomography for cardiac catheterization in select patients for evaluation of
      anatomy before second-stage single ventricle palliation. METHODS: This is a
      retrospective review of consecutive diagnostic cardiac catheterization (n=16) and
      computed tomography studies (n=16) performed before second-stage single ventricle
      palliation from March 2010 to July 2012 at a single institution. Risk
      (anesthesia, vascular access, contrast, and radiation exposure), accuracy, and
      postoperative course were compared. Nonparametric analysis was used to compare
      differences in group medians. RESULTS: General anesthesia was used for 16 of 16
      cardiac catheterization studies and 1 of 16 computed tomography studies. Vascular
      access was central venous and/or arterial for all cardiac catheterization studies
      and a peripheral intravenous line for all computed tomography studies. Median age
      and size-adjusted radiation dose was 14.0 mSv for cardiac catheterization and
      1.1 mSv for computed tomography. Contrast dose was 4.8 mL/kg for the cardiac
      catheterization group and 2 mL/kg for the computed tomography group. There were
      no computed tomography discrepancies and 1 discrepancy between cardiac
      catheterization and surgical findings. There were 8 adverse events in 6 patients
      in the cardiac catheterization group and 1 adverse event in the computed
      tomography group. There was no difference between groups in postoperative course
      or need for repeat intervention. CONCLUSIONS: Cardiac computed tomography and
      cardiac catheterization are equally accurate for evaluation of anatomy before
      second-stage single ventricle palliation when compared with surgical findings.
      Computed tomography may be the preferred test in select patients because of
      decreased vascular access and anesthesia risk, lower radiation and contrast
      exposure, and fewer adverse events.

PMID- 24930615
TI  - Bicuspid aortic valve repair by complete conversion from "raphe'd" (type 1) to
      "symmetric" (type 0) morphology.
AB  - OBJECTIVE: An anterior cusp with a median raphe and false commissure is the most
      common bicuspid aortic valve phenotype. The cusp is typically restricted and its
      annular attachment malpositioned, often resulting in significant aortic
      regurgitation. A novel valve repair strategy was designed to create a symmetric
      valve to improve both function and durability. METHODS: The technique involves
      converting the valve into a "symmetric" bicuspid valve by resection of the median
      raphe, with shortening of the anterior cusp's leading edge; resection of the
      false commissure with complete anterior annular detachment; enlargement,
      reinforcement, and translocation of the anterior cusp deeper into the left
      ventricular outflow tract; and valve-sparing aortic root replacement with
      concomitant annuloplasty. RESULTS: A total of 32 patients with a bicuspid valve,
      aortic insufficiency, and aortic dilatation have undergone valve repair with root
      replacement. No operative deaths or strokes occurred, and no permanent pacemakers
      were required. Thirteen patients underwent complete conversion from "raphe'd" to
      "symmetric" morphology; the others underwent less complex repairs without
      translocation. The postoperative transvalvular gradients remained normal. Freedom
      from grade >1+ aortic regurgitation and valve-related reoperation was 100%. All
      13 symmetric conversion patients have continued to have no or trace aortic
      regurgitation (grade < 1+) at a mean follow-up of 2.9 years (range, 0.4-7).
      CONCLUSIONS: Repair of the common, "raphe'd" bicuspid phenotype by
      reconfiguration into "symmetric" morphology is both feasible and desirable,
      regardless of the degree of preoperative aortic regurgitation. This repair
      strategy appears durable at the mid-term without evolving signs of deterioration
      or stenosis, offering a potentially superior option over prosthetic root
      replacement for younger patients.

PMID- 24930616
TI  - Endoscopic ultrasound-guided fine needle aspiration and endobronchial ultrasound
      guided transbronchial needle aspiration: Are two better than one in mediastinal
      staging of non-small cell lung cancer?
AB  - OBJECTIVE: The role of combined endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle
      aspiration (EUS-FNA) with a single bronchoscope is poorly understood. The purpose
      of the present study was to elucidate the roles of EBUS-TBNA and EUS-FNA with a
      single bronchoscope in the preoperative hilar and mediastinal staging of non
      small cell lung cancer (NSCLC). METHODS: A total of 150 patients with potentially
      resectable known or suspected NSCLC were enrolled in our prospective study. EBUS
      TBNA was performed, followed by EUS-FNA, with an EBUS bronchoscope for N2 and N3
      nodes>=5 mm in the shortest diameter on ultrasound images, in a single session.
      RESULTS: EBUS-TBNA was performed for 257 lymph nodes and EUS-FNA for 176 lymph
      nodes. Of the 150 patients, 146 had a final diagnosis of NSCLC. Of these 146
      patients, 33 (23%) had N2 and/or N3 nodal metastases. The sensitivity of EBUS
      TBNA, EUS-FNA, and the combined approach per patient was 52%, 45%, and 73%,
      respectively (EBUS-TBNA vs the combined approach, P=.016, McNemar's test). The
      corresponding negative predictive value was 88%, 86%, and 93%. Two patients (1%)
      developed severe cough from EBUS-TBNA. CONCLUSIONS: The combined endoscopic
      approach with EBUS-TBNA and EUS-FNA is a safe and accurate method for
      preoperative hilar and mediastinal staging of NSCLC, with better results than
      with each technique by itself.

PMID- 24930617
TI  - Residual and recurrent gradients after septal myectomy for hypertrophic
      cardiomyopathy-mechanisms of obstruction and outcomes of reoperation.
AB  - OBJECTIVE: The aims of the present study were to identify the mechanisms of
      residual or recurrent left ventricular outflow tract obstruction in patients
      undergoing repeat septal myectomy for hypertrophic cardiomyopathy and to assess
      the early and late results of reoperation. METHODS: From January 1980 to June
      2012, we performed 52 repeat myectomies in 51 patients. We reviewed the medical
      records and preoperative transthoracic echocardiograms to evaluate the adequacy
      of the previous resection and mechanism of left ventricular outflow tract
      obstruction. The complications of previous and repeat myectomy, New York Heart
      Association class, and survival were analyzed. RESULTS: The mean interval from
      previous myectomy to reoperation was 43 +/- 51 months. In 6 patients (12%)
      residual or recurrent gradients were caused by isolated midventricular
      obstruction. In the remaining 46 operations, the mechanism of residual or
      recurrent gradients was identified as systolic anterior motion of mitral valve
      related subaortic obstruction caused by inadequate length of previous subaortic
      septal excision in 31 patients (59% of the total), both an inadequate length and
      an inadequate depth of septectomy in 13 patients (25%), and both residual
      subaortic obstruction due to systolic anterior motion of the mitral valve and
      midventricular obstruction in 2 patients (4%). Preoperatively, 96% of patients
      were in New York Heart Association class III or IV; postoperatively, 93.8% were
      in class I or II (P < .001). The 10-year survival after reoperation was 98% and
      similar to that of an age- and gender-matched Minnesota population (P = .46).
      CONCLUSIONS: The most common cause of recurrent left ventricular outflow tract
      obstruction and symptoms in patients undergoing septal myectomy has been an
      inadequate length of septal excision. Reoperation is safe, with excellent long
      term survival and functional improvement.

PMID- 24930618
TI  - Scoring system to guide decision making for the use of gentamicin-impregnated
      collagen sponge to prevent deep sternal wound infection.
AB  - OBJECTIVES: The effectiveness of the routine retrosternal placement of a
      gentamicin-impregnated collagen sponge (GICS) implant before sternotomy closure
      is currently a matter of some controversy. We aimed to develop a scoring system
      to guide decision making for the use of GICS to prevent deep sternal wound
      infection. METHODS: Fast backward elimination on predictors, including GICS, was
      performed using the Lawless and Singhal method. The scoring system was reported
      as a partial nomogram that can be used to manually obtain predicted individual
      risk of deep sternal wound infection from the regression model. Bootstrapping
      validation of the regression models was performed. RESULTS: The final populations
      consisted of 8750 adult patients undergoing cardiac surgery through full
      sternotomy during the study period. A total of 329 patients (3.8%) received GICS
      implant. The overall incidence of deep sternal wound infection was lower among
      patients who received GICS implant (0.6%) than patients who did not (2.01%)
      (P=.02). A nomogram to predict the individual risk for deep sternal wound
      infection was developed that included the use of GICS. Bootstrapping validation
      confirmed a good discriminative power of the models. CONCLUSIONS: The scoring
      system provides an impartial assessment of the decision-making process for
      clinicians to establish if GICS implant is effective in reducing the risk for
      deep sternal wound infection in individual patients undergoing cardiac surgery
      through full sternotomy.

PMID- 24930621
TI  - Injection laryngoplasty in the outpatient clinic under local anaesthetic: a case
      series of sixty-eight patients.
AB  - OBJECTIVES: We aimed to assess self-report and perceptual voice outcomes in
      patients undergoing local anaesthetic injection laryngoplasty in our outpatient
      clinic. DESIGN: Prospective case series. SETTING: Department of Otolaryngology
      Head and Neck Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK. PARTICIPANTS:
      Sixty-eight patients underwent local anaesthetic injection laryngoplasty in the
      outpatient clinic over the 2-year study period. MAIN OUTCOME MEASURE: Voice
      Performance Questionnaire (patient-rated), and perceptual voice analysis
      (observer-rated) Grade, Roughness, Breathiness, Aesthenia and Strain scores were
      recorded before and 2 weeks after injection laryngoplasty. RESULTS: Fifty-seven
      patients had sufficient pre- and post-procedure data to be included in the
      analysis. These included 32 men and 25 women, age range 26-97 years. Of the
      remaining patients, they were excluded due to failed procedure (n = 3), too
      unwell to proceed (n = 1), died before follow-up was complete (n = 3) and
      incomplete data (n = 4). The median Voice Performance Questionnaire score
      improved from 42 to 21; (P < 0.0001). Significant improvements were seen in all
      parameters of Grade, Roughness, Breathiness, Aesthenia, Strain. CONCLUSION:
      Injection laryngoplasty under local anaesthetic in the outpatient clinic
      generates improvements in subjective and perceptual voice outcomes similar to
      those obtained in the operating room under general anaesthetic or sedation.
      Complication rates between these procedures were also comparable. Injection
      laryngoplasty under local anaesthetic is timely, cost-effective and obviates need
      for general anaesthesia in patients, many of whom have comorbidities and
      diminished life expectancy.

PMID- 24930620
TI  - Incidence and cost of sexual violence in Iowa.
AB  - BACKGROUND: Sexual violence is a serious and costly public health problem.
      Current research that systematically documents the broad range of economic costs
      of sexual violence is lacking. PURPOSE: To estimate the incidence and costs of
      sexual violence in Iowa in 2009. METHODS: Using data obtained from population
      surveys, six Iowa government agencies, and other sources, we estimated sexual
      violence incidence, costs per incident, and total costs in 2009 dollars, by age
      and sexual violence category, and for various cost elements. We calculated direct
      costs of medical care, mental health care, property damage, victim services,
      investigation, adjudication, and sanctioning, as well as indirect costs for lost
      work and quality of life. We collected data in 2010-2011 and completed analysis
      in 2013. RESULTS: In 2009, an estimated 55,340 individuals experienced sexual
      violence in Iowa, including 49,510 adults and 5,930 children. Nearly three of
      every four victims were women. The estimated total cost of sexual violence in
      2009 was $4.7 billion, equating to $1,580 per resident. This estimate included
      $4.44 billion in indirect costs and $265 million in direct costs. In the same
      year, the government spent an estimated $100.6 million as a result of sexual
      violence in Iowa, more than half of which ($55.3 million) was spent on
      perpetrators and little ($0.9 million) on prevention. CONCLUSIONS: The economic
      costs of sexual violence are high for individuals and society. Cost information
      can help identify the burden of sexual violence relative to other social problems
      in Iowa and prioritize funding for prevention and intervention.

PMID- 24930619
TI  - Safety and toxicity of radioembolization plus Sorafenib in advanced
      hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC.
AB  - BACKGROUND & AIMS: The benefits of combined systemic and liver-directed
      treatments in inoperable intermediate- or advanced-stage hepatocellular carcinoma
      (HCC) have yet to be defined. This article presents the planned safety analyses
      for the first 40 patients randomized to radioembolization with yttrium-90 ((90)
      Y) resin microspheres followed by sorafenib (n = 20) or sorafenib only (n = 20)
      in the SORAMIC study. METHODS: Patients identified for palliative treatment who
      were poor candidates for transarterial (chemo)embolization (including those
      failing TACE) with preserved liver function (Child-Pugh <=B7) and ECOG
      performance status <2 were screened. Radioembolization was administered using a
      sequential lobar approach. On day 3 after the last radioembolization procedure,
      sorafenib 200 mg twice daily was initiated escalating to 400 mg twice daily 1
      week later; a matching sorafenib dose schedule was initiated in the control arm.
      RESULTS: Patients were followed up for a median of 8.3 months. Median total
      implanted activity of (90) Y was 1.87 (range: 0.54-2.35) GBq. Patients received a
      similar intensity and duration of sorafenib in the combination-treatment arm
      (median daily dose 614 mg over 8.5 months) and control arm (557 mg over 9.6
      months). The incidence of total (196 vs. 222) and grade >=3 (43 vs. 47) adverse
      events was similar in combination-treatment arm and control arm respectively (P >
      0.05). No significant differences in the number of total or grade 3/4 toxicities
      were recorded for: total bilirubin, albumin, liver enzymes, ascites, Child-Pugh,
      fatigue, hand-foot skin reaction, blood pressure or diarrhoea. CONCLUSIONS:
      Radioembolization followed by sorafenib appears to be as well tolerated as
      sorafenib alone.

PMID- 24930622
TI  - Corneal thickness in children with growth hormone deficiency: the effect of GH
      treatment.
AB  - OBJECTIVE: The eye represents a target site for GH action, although few data are
      available in patients with GH deficiency (GHD). Our aim was to evaluate central
      corneal thickness (CCT) and intraocular pressure (IOP) values in GHD children to
      assess the role played by GHD or GH treatment on these parameters. DESIGN: In 74
      prepubertal GHD children (51M, 23F, aged 10.4+/-2.4years) we measured CCT and IOP
      before and after 12months of treatment. A baseline evaluation was also made in 50
      healthy children matched for age, gender and body mass index. The study outcome
      considered CCT and IOP during treatment and their correlations with biochemical
      and auxological data. RESULTS: No difference in CCT and IOP between GHD children
      at baseline and controls was found (all p>0.005). GHD children after 12months of
      therapy showed greater CCT (564.7+/-13.1MUm) than both baseline values (535.7+/
      17MUm; p<0.001) and control subjects (536.2+/-12.5MUm; p<0.001), with a
      concomitantly higher corrected mean IOP (15.6+/-0.7mmHg; p<0.001) than both
      baseline (12.5+/-0.8mmHg; p<0.001) and controls (12.3+/-0.5mmHg; p<0.001),
      without correlation with auxological and biochemical parameters. CONCLUSIONS:
      12months of GH treatment in children with GHD, regardless of auxological and
      biochemical data, affect CCT and IOP. Our findings suggest careful ocular
      evaluation in these patients to prevent undesirable side effects during the
      follow-up.

PMID- 24930623
TI  - Disease-free survival as an end-point in the treatment of solid tumours-
      perspectives from clinical trials and clinical practice.
AB  - Disease-free survival (DFS) is an end-point for an increasing number of clinical
      trials in adjuvant and curative intent cancer treatment informing both regulatory
      bodies and clinical practice. DFS is seen both as a surrogate end-point and as an
      end-point in itself in clinical trials. Understanding the history of DFS, and
      some of the assumptions, limitations, and vulnerabilities for studies designed
      with this primary end-point are required. This commentary reviews recent drug
      approvals for anti-cancer agents in solid tumours in the adjuvant and curative
      settings, and considers the meaning of DFS from the perspectives of clinical
      trials and clinical practice. 

PMID- 24930626
TI  - Decreased toxicity with 2 weeks on and 1 week off schedule of sunitinib in
      metastatic renal cell carcinoma: is it a mirage or an oasis?

PMID- 24930624
TI  - Cardiovascular events among 1090 cancer patients treated with sunitinib,
      interferon, or placebo: a comprehensive adjudicated database analysis
      demonstrating clinically meaningful reversibility of cardiac events.
AB  - PURPOSE: To define cardiovascular (CV) risk and reversibility of cardiac events
      in patients who received sunitinib versus comparator treatment (interferon-alfa
      or placebo). PATIENTS AND METHODS: We performed a retrospective adjudication of
      comprehensive CV adverse events (AEs) from two phase 3 trials. Components of the
      comprehensive CV AE end-point comprised hypertension, symptomatic and
      asymptomatic left ventricular ejection fraction decreases (SD-LVEF; AD-LVEF) and
      extent of reversibility, heart-failure symptoms, thromboembolic events,
      dysrhythmia and CV death. Three cardiologists and one oncologist, blinded to
      treatment allocation, adjudicated suspected CV AEs in the pooled trial database
      (N=1090). RESULTS: Incidence rates (IR) for sunitinib versus Interferon-alfa (IFN
      alpha)/placebo were hypertension: 6.9 versus 2.6 (hazard ratio (HR), 3.1; 95%
      confidence interval (CI), 2.4-4.0); SD-LVEF: 0.4 versus 0.2 (HR, 2.5; 95% CI, 1.0
      6.2); AD-LVEF: 1.1 versus 0.8 (HR, 2.1; 95% CI, 1.3-3.4); and composite CV AE end
      point: 10.1 versus 4.8 (HR, 2.5; 95% CI, 2.0-3.1), however reversibility, not
      previously quantified, was found to be clinically meaningful. CONCLUSIONS:
      Hypertension and SD-LVEF/AD-LVEF were significantly higher with sunitinib versus
      IFN-alpha/placebo. Among patients who experienced a cardiac event, symptomatic
      and asymptomatic instances of decreased cardiac dysfunction were adjudicated as
      reversible in 47 of 83 (56%) and 17 of 30 (57%), respectively. Among sunitinib
      treated patients, many were able to resume sunitinib dosing following resolution
      of events, a finding that is important for clinical care. In comparator groups,
      symptomatic and asymptomatic instances were adjudicated as reversible in 4 of 6
      (66.7%) and 11 of 21 (52%), respectively. Thromboembolic, dysrhythmic and/or CV
      deaths were not significantly higher in sunitinib-treated patients.

PMID- 24930625
TI  - A phase 2 randomised study of ramucirumab (IMC-1121B) with or without dacarbazine
      in patients with metastatic melanoma.
AB  - BACKGROUND: To evaluate the efficacy and safety of ramucirumab (IMC-1121B;
      LY3009806), a fully human monoclonal antibody targeting the vascular endothelial
      growth factor receptor-2, alone and in combination with dacarbazine in
      chemotherapy-naive patients with metastatic melanoma (MM). METHODS: Eligible
      patients received ramucirumab (10mg/kg) + dacarbazine (1000 mg/m(2)) (Arm A) or
      ramucirumab only (10mg/kg) (Arm B) every 3 weeks. The primary end-point was
      progression-free survival (PFS); secondary end-points included overall survival
      (OS), overall response and safety. FINDINGS: Of 106 randomised patients, 102
      received study treatment (Arm A, N=52; Arm B, N=50). Baseline characteristics
      were similar in both arms. Median PFS was 2.6 months (Arm A) and 1.7 months (Arm
      B); median 6-month PFS rates were 30.7% and 17.9% and 12-month PFS rates were
      23.7% and 15.6%, respectively. In Arm A, 9 (17.3%) patients had partial response
      (PR) and 19 (36.5%), stable disease (SD); PR and SD in Arm B were 2 (4.0%) and 21
      (42.0%), respectively. Median OS was 8.7 months in Arm A and 11.1 months in Arm
      B. Patients in both arms tolerated the treatment with limited Grade 3/4
      toxicities. INTERPRETATION: Ramucirumab alone or in combination with dacarbazine
      was associated with an acceptable safety profile in patients with MM. Although
      the study was not powered for comparison between treatment arms, PFS appeared
      greater with combination therapy. Sustained disease control was observed on both
      study arm.

PMID- 24930627
TI  - Analgesic efficacy and safety of single-dose tramadol and non-steroidal anti
      inflammatory drugs in operations on the third molars: a systematic review and
      meta-analysis.
AB  - The aim of this systematic review and meta-analysis was to evaluate published
      randomised, double-blind, clinical trials to compare the analgesic efficacy and
      safety of tramadol with that of non-steroidal anti-inflammatory drugs (NSAID) in
      operations on the third molars. We identified eligible reports from searches of
      PubMed, MedLine, the Cochrane Library, Oxford Pain Relief database, Imbiomed, and
      Google Scholar. The full text of studies that met our minimum requirements were
      evaluated using inclusion and exclusion criteria with the Oxford Quality Scale.
      Those with a Score >= 3 in this scale were included and their data were extracted
      and analysed. Absolute increase in risk, the number needed to harm, odds ratio
      and 95% CI were calculated using Risk Reduction Calculator software. Each meta
      analysis was made with the help of the Mantel-Haenszel random effects model,
      estimates of risk (odds ratio (OR)) and 95% CI were calculated using the Review
      Manager 5.2. from the Cochrane Library. A significant risk was assumed when the
      lower limit of the 95%CI was greater than 1. Probabilities of less than 0.05 were
      accepted as significant. The results showed that tramadol had less analgesic
      efficacy and an increased risk of adverse effects compared with NSAID. In
      conclusion, a single dose of tramadol was not as effective or as safe as NSAID
      for the relief of pain after operations on the third molars. 

PMID- 24930628
TI  - Effect of genotype, gender and age on sheep meat quality and a case study
      illustrating integration of knowledge.
AB  - Subtle breed differences exist for meat quality traits and the Merino does stand
      out, although many comparisons are confounded by production site or lack of
      processing intervention. Despite this, the Merino does seem to have a propensity
      to produce meat with a higher pH and reduced colour stability under extended
      ageing. Use of the Merino in a crossbreeding system not only provides benefits
      from hybrid vigour, but also overcomes the meat quality constraints of pure
      Merinos. Genetic evaluation for lamb production has enabled impressive genetic
      gains, but an overemphasis on lean meat production has had to be addressed to
      counter adverse effects on meat quality traits like eating quality. In this
      regard, the development of genomic selection has provided a methodology for
      accurate prediction of genetic merit and applying balanced breeding objectives.
      The potential for negative meat quality effects has stemmed adoption of non
      castration approaches, but ensuring that lamb is young when slaughtered does
      provide brand integrity. 

PMID- 24930629
TI  - B7 costimulation and intracellular indoleamine 2,3-dioxygenase expression in
      umbilical cord blood and adult peripheral blood.
AB  - Alterations in the expression of B7 costimulatory molecules and their receptors,
      as well as differences in the tryptophan (TRP) catabolic pathway, may influence
      immunological reactivity of umbilical cord blood (UCB) compared with adult
      peripheral blood (APB) T lymphocytes. We determined the frequency of activated
      (CD11b(+)) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2, and that of T cells
      and CD4(+) T helper cells expressing CD28, cytotoxic T lymphocyte antigen 4 (CTLA
      4), programmed death-1 receptor, and inducible costimulator of T cells in UCB and
      APB samples using flow cytometry. We also examined the intracellular expression
      of indoleamine 2,3-dioxygenase (IDO) applying flow cytometry and plasma levels of
      TRP, kynurenine (KYN), and kynurenic acid using high-performance liquid
      chromatography. The level of CTLA-4 expression on CD4 cells was higher in UCB
      compared with in APB, indicating that the possibility of CD28-mediated
      costimulation may be decreased. The level of the corresponding costimulator
      molecule, B7-2, was also elevated. Therefore, this inhibitory relation may
      function to a higher extent in UCB than in APB. The plasma KYN to TRP (K/T) ratio
      was 2-fold higher in UCB compared with APB. However, the capacity of UCB
      monocytes to produce IDO compared with APB monocytes was lower, and reverse
      signaling via B7-2 in UCB monocytes was found to be immature, which suggests that
      the observed increase in K/T ratio may be due to placental, rather than fetal,
      overexpression of IDO in competent cells. These factors may all contribute to the
      previously observed reduced reactivity of UCB T lymphocytes compared to APB T
      cells. 

PMID- 24930631
TI  - A continental scale trophic cascade from wolves through coyotes to foxes.
AB  - Top-down processes, via the direct and indirect effects of interspecific
      competitive killing (no consumption of the kill) or intraguild predation
      (consumption of the kill), can potentially influence the spatial distribution of
      terrestrial predators, but few studies have demonstrated the phenomenon at a
      continental scale. For example, in North America, grey wolves Canis lupus are
      known to kill coyotes Canis latrans, and coyotes, in turn, may kill foxes Vulpes
      spp., but the spatial effects of these competitive interactions at large scales
      are unknown. Here, we analyse fur return data across eight jurisdictions in North
      America to test whether the presence or absence of wolves has caused a continent
      wide shift in coyote and red fox Vulpes vulpes density. Our results support the
      existence of a continental scale cascade whereby coyotes outnumber red foxes in
      areas where wolves have been extirpated by humans, whereas red foxes outnumber
      coyotes in areas where wolves are present. However, for a distance of up to 200
      km on the edge of wolf distribution, there is a transition zone where the effects
      of top-down control are weakened, possibly due to the rapid dispersal and
      reinvasion capabilities of coyotes into areas where wolves are sporadically
      distributed or at low densities. Our results have implications for understanding
      how the restoration of wolf populations across North America could potentially
      affect co-occurring predators and prey. We conclude that large carnivores may
      need to occupy large continuous areas to facilitate among-carnivore cascades and
      that studies of small areas may not be indicative of the effects of top-down
      mesopredator control. 

PMID- 24930630
TI  - Lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic
      enlargement and erectile dysfunction: are these conditions related to vascular
      dysfunction?
AB  - Although the pathogenesis of lower urinary tract symptoms, benign prostatic
      hyperplasia/benign prostatic enlargement and erectile dysfunction is poorly
      understood and thought to be multifactorial, it has been traditionally recognized
      that these conditions increase with age. There is increasing evidence that there
      is an association between cardiovascular disease and lower urinary tract symptoms
      as well as benign prostatic hyperplasia/benign prostatic enlargement and erectile
      dysfunction in elderly patients. Age might activate systemic vascular risk
      factors, resulting in disturbed blood flow. Hypertension, diabetes,
      hyperlipidemia and atherosclerosis are also linked to the etiology of lower
      urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement
      and erectile dysfunction. In the present review, we discuss the relationship
      between decreased pelvic blood flow and lower urinary tract symptoms, benign
      prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction.
      Furthermore, we suggest possible common mechanisms underlining these urological
      conditions. 

PMID- 24930633
TI  - Cloning of the Arabidopsis rwm1 gene for resistance to Watermelon mosaic virus
      points to a new function for natural virus resistance genes.
AB  - Arabidopsis thaliana represents a valuable and efficient model to understand
      mechanisms underlying plant susceptibility to viral diseases. Here, we describe
      the identification and molecular cloning of a new gene responsible for recessive
      resistance to several isolates of Watermelon mosaic virus (WMV, genus Potyvirus)
      in the Arabidopsis Cvi-0 accession. rwm1 acts at an early stage of infection by
      impairing viral accumulation in initially infected leaf tissues. Map-based
      cloning delimited rwm1 on chromosome 1 in a 114-kb region containing 30 annotated
      genes. Positional and functional candidate gene analysis suggested that rwm1
      encodes cPGK2 (At1g56190), an evolutionary conserved nucleus-encoded chloroplast
      phosphoglycerate kinase with a key role in cell metabolism. Comparative sequence
      analysis indicates that a single amino acid substitution (S78G) in the N-terminal
      domain of cPGK2 is involved in rwm1-mediated resistance. This mutation may have
      functional consequences because it targets a highly conserved residue, affects a
      putative phosphorylation site and occurs within a predicted nuclear localization
      signal. Transgenic complementation in Arabidopsis together with virus-induced
      gene silencing in Nicotiana benthamiana confirmed that cPGK2 corresponds to rwm1
      and that the protein is required for efficient WMV infection. This work uncovers
      new insight into natural plant resistance mechanisms that may provide interesting
      opportunities for the genetic control of plant virus diseases. 

PMID- 24930634
TI  - Intramedullary craniovertebral junction tuberculoma: An uncommon location of a
      common disease.
AB  - Central nervous system involvement is observed in no more than 10% of patients
      with systemic tuberculosis. Although CNS tuberculosis is not rare in endemic
      countries, such as India, intramedullary tuberculosis is not commonly reported.
      In this study, we report a case of a 40-year-old female who presented with a six
      year history of insidious onset, gradually progressive, asymmetric quadriparesis.
      She was diagnosed with intramedullary tuberculoma at the craniovertebral junction
      and showed significant clinico-radiological improvement with medical management
      alone. To the best of our knowledge, this report describes the first case of
      intramedullary tuberculoma at the craniovertebral junction to be reported. With
      the increased availability of MRI in developing countries, it is now possible for
      clinicians to diagnose this condition without performing a biopsy. It is
      important for the clinicians in developed countries to be highly suspicious of
      intramedullary tuberculoma, as there has been a resurgence of CNS tuberculosis
      due to the emergence of the HIV pandemic. 

PMID- 24930635
TI  - Novel protocol including liver biopsy to identify and treat CD8+ T-cell
      predominant acute hepatitis and liver failure.
AB  - In the majority of children with ALF, the etiology is unknown and liver
      transplantation is often needed for survival. A patient case prompted us to
      consider that immune dysregulation may be the cause of indeterminate acute
      hepatitis and liver failure in children. Our study includes nine pediatric
      patients treated under a multidisciplinary clinical protocol to identify and
      treat immune-mediated acute liver injury. Patients with evidence of inflammation
      and no active infection on biopsy received treatment with intravenous immune
      globulin and methylprednisolone. Seven patients had at least one positive immune
      marker before or after treatment. All patients had a CD8+ T-cell predominant
      liver injury that completely or partially responded to immune therapy. Five of
      the nine patients recovered liver function and did not require liver
      transplantation. Three of these patients subsequently developed bone marrow
      failure and were treated with either immunosuppression or stem cell transplant.
      This series highlights the importance of this tissue-based approach to diagnosis
      and treatment that may improve transplant-free survival. Further research is
      necessary to better characterize the immune injury and to predict the subset of
      patients at risk for bone marrow failure who may benefit from earlier and
      stronger immunosuppressive therapy. 

PMID- 24930632
TI  - MT-7716, a potent NOP receptor agonist, preferentially reduces ethanol seeking
      and reinforcement in post-dependent rats.
AB  - Dysregulation of the nociceptin (N/OFQ) system has been implicated in alcohol
      abuse and alcoholism, and growing evidence suggests that targeting this system
      may be beneficial for treating alcoholism. To further explore the treatment
      target potential of the N/OFQ system, the novel non-peptide, small-molecule N/OFQ
      (NOP) agonist MT-7716, (R)-2-{3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3
      dihydro-1H-benzimidazol-1-yl}-N-methylacetamide hydrochloride hydrate, was
      examined for its effects on ethanol self-administration and stress-induced
      reinstatement of alcohol seeking in non-dependent and post-dependent rats. Male
      Wistar rats were trained to self-administer ethanol and then made ethanol
      dependent via repeated intragastric ethanol intubation. The effects of MT-7716
      (0.3 and 1 mg/kg; PO) on alcohol self-administration were determined 2 weeks
      following dependence induction, when baseline self-administration was restored.
      Effects of MT-7716 on stress-induced reinstatement were tested in separate
      cohorts of rats, 1 and 3 weeks post-withdrawal. MT-7716 reduced alcohol self
      administration and stress-induced reinstatement of alcohol seeking in post
      dependent rats, but was ineffective in non-dependent animals. Moreover, the
      prevention of stress-induced reinstatement by MT-7716 was more pronounced at 3
      weeks post-dependence. The results further confirm treatment target potential for
      the NOP receptor and identify non-peptide NOP agonists as promising potential
      treatment drugs for alcohol abuse and relapse prevention. The findings also
      support dysregulation of the N/OFQ system as a factor in alcohol seeking and
      reinforcement.

PMID- 24930636
TI  - Defining acceptable epidemiology ranges in donor populations based on the
      contamination risk of finished plasma-derived products.
AB  - BACKGROUND: For a given plasma-derived product, the risk of final product
      contamination by hepatitis B virus, hepatitis C virus and human immunodeficiency
      virus depends upon the epidemiology in the donor population, the virus load in a
      donation, the product yield and the effective virus reduction capacity in
      manufacturing. STUDY DESIGN AND METHODS: A Monte Carlo simulation model was
      developed to estimate the risk of virus contamination of a final product
      resulting from virus contamination of plasma pools for fractionation. The model
      was run for both source and recovered plasma at various incidence rates for the
      three viruses to determine virus loads in minipools and fractionation pools
      resulting from donations with virus levels below test sensitivities. Together
      with the virus reduction capacity and yield of a theoretical worst case plasma
      derived product, the contamination risk in a final vial was calculated. RESULTS:
      Acceptable upper-bound centre-level incidence rates in the donor population (per
      donor centre) result in final products with very high margins of virus safety;
      the largest determinant of these 'Process Limits' is the virus reduction capacity
      of the manufacturing process. Short donation intervals and long inventory hold
      periods for source plasma compensates the lower incidence rates typically
      observed in recovered plasma donors. CONCLUSIONS: The model calculates process
      limits for epidemiological data at collection centres based on an appropriate
      margin of virus safety for final products. The model also takes into
      consideration the impact of different donor/donation management systems for
      source and recovered plasma on the number of low viraemic donations entering the
      plasma pool for fractionation.

PMID- 24930637
TI  - Trapping and release of giant unilamellar vesicles in microfluidic wells.
AB  - We describe the trapping and release of giant unilamellar vesicles (GUVs) in a
      thin and wide microfluidic channel, as they cross indentations etched in the
      channel ceiling. This trapping results from the reduction of the membrane elastic
      energy, which is stored in the GUV as it squeezes to enter into the thin channel.
      We demonstrate that GUVs whose diameter is slightly larger than the channel
      height can be trapped and that they can be untrapped by flowing the outer fluid
      beyond a critical velocity. GUVs smaller than the channel height flow undisturbed
      while those much larger cannot squeeze into the thin regions. Within the range
      that allows trapping, larger GUVs are anchored more strongly than smaller GUVs.
      The ability to trap vesicles provides optical access to the GUVs for extended
      periods of time; this allows the observation of recirculation flows on the
      surface of the GUVs, in the forward direction near the mid-plane of the channel
      and in the reverse direction elsewhere. We also obtain the shape of GUVs under
      different flow conditions through confocal microscopy. This geometric information
      is used to derive a mechanical model of the force balance that equates the
      viscous effects from the outer flow with the elastic effects based on the
      variation of the membrane stretching energy. This model yields good agreement
      with the experimental data when values of the stretching moduli are taken from
      the scientific literature. This microfluidic approach provides a new way of
      storing a large number of GUVs at specific locations, with or without the
      presence of an outer flow. As such, it constitutes a high-throughput alternative
      to micropipette manipulation of individual GUVs for chemical or biological
      applications. 

PMID- 24930638
TI  - Evaluating the contributions of change in investment and change in efficiency to
      age-related declines in male and female reproduction.
AB  - It is commonly observed that reproduction decreases with age, often at a
      different rate in males and females. This phenomenon is generally interpreted as
      senescence. Such reproductive declines may stem from at least two sources: a
      change in resource allocation and a decline in the ability to convert resources
      into offspring. This distinction is important because a shift in resource
      allocation may be favoured by selection, while reduced efficiency is purely
      deleterious. We propose a way to distinguish whether a decline in reproduction is
      purely deleterious based on estimating reproductive investment, output, and their
      ratio, efficiency. We apply this approach to the hermaphroditic snail Physa acuta
      and demonstrate that both male and female functions decline with age. The male
      decline largely stems from reduced investment into male activity while female
      decline is due to increased reproductive inefficiency. This shows that age
      related declines in reproduction can occur for a number of different reasons, a
      distinction that is usually masked by the general term 'senescence'. This
      approach could be applied to any species to evaluate age-related reproductive
      decline. We advocate that future studies measure age trajectories of reproductive
      investment and output to explore the potential processes hidden behind the
      observation that reproduction declines with age. 

PMID- 24930640
TI  - Environmentally benign technology for efficient warm-white light emission.
AB  - Nowadays efficient down conversion for white light emission is mainly based on
      rare-earth doped phosphors or cadmium-containing quantum dots. Although they
      exhibit high luminescence efficiency, the rare-earth mining and cadmium pollution
      have so far led to extremely high environmental cost, which conflicts the
      original purpose of pursuing efficient lighting. Here, we explore a new strategy
      to achieve efficient luminescence conversion based on polymer-decorated
      nanoparticles. The ZnO and Mn(2+) doped ZnS nanoparticles are encapsulated by
      poly(9,9-di-n- hexylfluorenyl-2,7-diyl). The resultant core-shell nanocomposites
      then encompass three UV-to-visible luminescence conversion routes for photon
      emissions at blue, green, and orange colors, respectively. As a result, the color
      temperature is widely tunable (2100 K ~ 6000 K), so candle light or pure white
      light can be generated. The quantum yield up to 91% could also be achieved. Such
      rare-earth-element free nanocomposites give the bright perspectives for energy
      saving, healthy, and environmentally benign lighting.

PMID- 24930639
TI  - Metronidazole and amoxicillin as adjuncts to scaling and root planing for the
      treatment of type 2 diabetic subjects with periodontitis: 1-year outcomes of a
      randomized placebo-controlled clinical trial.
AB  - AIM: To evaluate the clinical and microbiological effects of the use of
      metronidazole (MTZ) + amoxicillin (AMX) as adjuncts to scaling and root planing
      (SRP) for the treatment of chronic periodontitis (ChP) in type 2 diabetic
      subjects. MATERIAL AND METHODS: Fifty-eight type 2 diabetic subjects (n =
      29/group) with generalized ChP were randomly assigned to receive SRP alone or
      with MTZ [400 mg/thrice a day (TID)]+AMX (500 mg/TID) for 14 days. Subgingival
      biofilm samples were analyzed by qPCR for the presence of seven periodontal
      pathogens. Subjects were monitored at baseline, 3, 6 and 12 months post
      therapies. RESULTS: The group receiving SRP+MTZ+AMX presented greater mean
      probing depth (PD) reduction and clinical attachment gain, a lower number of
      sites with PD >=5 mm (primary outcome variable) and a reduced number of subjects
      with >=9 of these residual pockets than the control group at 1-year post-therapy
      (p < 0.05). The antibiotic-treated group also presented reduced levels and
      greater decreases of the three red complex species, Eubacterium nodatum and
      Prevotella intermedia, compared to the control group at 1 year (p < 0.05).
      CONCLUSIONS: The adjunctive use of MTZ+AMX significantly improved the clinical
      and microbiological outcomes of SRP in the treatment of type 2 diabetic subjects
      with ChP.

PMID- 24930641
TI  - Efficacy and safety of proton pump inhibitors (PPIs) plus rebamipide for
      endoscopic submucosal dissection-induced ulcers: a meta-analysis.
AB  - OBJECTIVE: To compare the efficacy of proton pump inhibitors (PPIs) with
      rebamipide versus PPIs alone for the treatment of ulcers after endoscopic
      submucosal dissection (ESD). METHODS: PubMed, Web of Science, Medline, Embase,
      the Cochrane Central Register of Controlled Trials and China Naitonal Knowledge
      Infrastructure were searched up to the end of October 2013 in order to identify
      all randomized controlled trials reporting the effects of PPIs plus rebamipide on
      healing ulcers after ESD. The outcome measurement was complete ulcer healing.
      RESULTS: A total of six studies involving 724 patients were included. The pooled
      data suggested a significantly higher rate of ulcer healing after endoscopic
      therapy among patients treated with PPIs plus rebamipide than among those treated
      with PPIs alone [odds ratio (OR)=2.40, 95% confidence interval (CI): 1.68-3.44].
      The subgroup analysis showed PPI plus rebamipide therapy to be more effective in
      healing ESD-induced ulcers than treatment with PPIs alone after both four
      (OR=2.22, 95%CI: 1.53-3.24) and eight weeks of treatment (OR=3.19, 95%CI: 1.22
      8.31). In addition, the combination therapy was found to be significantly more
      effective than the use of PPIs alone for all ESD ulcers greater than 20 mm in
      size (OR=4.77, 95%CI: 2.22-10.26). There were no significant differences between
      the treatment groups with regard to ulcer location (low, middle or upper stomach)
      or the presence of absence of H. pylori infection. No serious adverse events were
      observed in either group. CONCLUSION: The results of this meta-analysis suggest
      that treatment with PPIs plus rebamipide is superior to PPI monotherapy for
      healing ESD-induced ulcers over four weeks, particularly large ulcers. However,
      more well-designed trials are needed to confirm these findings.

PMID- 24930642
TI  - Investigation of ornithine carbamoyltransferase as a biomarker of liver
      cirrhosis.
AB  - OBJECTIVE: Ornithine carbamoyltransferase (OCT) is a liver-specific mitochondrial
      matrix enzyme and potential biomarker of liver fibrosis. This study investigated
      the OCT levels in patients with chronic liver disease with or without cirrhosis
      in order to assess the usefulness of OCT as a biomarker of cirrhosis. METHODS:
      The subjects included 440 Japanese patients with chronic liver disease and 80
      control subjects. The patients were divided into two groups, those with and
      without cirrhosis, both of which were further stratified into high-OCT and low
      OCT subgroups. RESULTS: In the non-cirrhosis group, the patients with non
      alcoholic steatohepatitis (NASH), alcoholic liver disease, primary biliary
      cirrhosis and primary sclerosing cholangitis (PSC) comprised the high-OCT
      subgroup, while the patients with hepatitis B, hepatitis C and autoimmune
      hepatitis formed the low-OCT subgroup. There were significant differences in the
      OCT levels, OCT/aspartate aminotransferase ratios and OCT/alanine transaminase
      (ALT) ratios between these two subgroups (p<0.001). The same findings were
      observed in the cirrhosis group. The OCT levels were markedly higher in the
      cirrhosis group than in the non-cirrhosis group, particularly among the patients
      with PSC (p<0.001). The most useful biomarker for predicting cirrhosis was the
      OCT/ALT ratio in the patients with hepatitis C and NASH and the OCT level in
      patients with PSC. CONCLUSION: The OCT level differs among patients with
      different chronic liver diseases. The role of OCT should be further evaluated in
      order to improve our understanding of the pathogenesis of these diseases. The OCT
      level is a useful surrogate marker of cirrhosis, particularly in PSC patients.

PMID- 24930643
TI  - Relationship between fatty liver disease and intracranial main artery stenosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between fatty
      liver disease (FLD) and cerebrovascular disease. METHODS: We conducted a cross
      sectional study of 76 consecutive healthy subjects who participated in a two-day
      hospitalized health checkup program. The maximal intima-media thickness (IMT) of
      the common carotid artery and bifurcation of the carotid artery as well as the
      plaque score (PS) were evaluated on carotid artery ultrasonography. Fluid
      attenuated inversion recovery brain MRI was used to determine the presence of
      asymptomatic cerebral lesions and periventricular hyperintensity. Brain MR
      angiography was used to evaluate the degree of intracranial main artery stenosis
      (ICAS). FLD was diagnosed based on the ultrasonographic pattern. RESULTS: The PS
      and IMT did not differ between the FLD (n=24) and non-FLD (n=52) groups. There
      was a tendency toward a higher percentage of multiple lacunar lesions in the non
      FLD group than in the FLD group. ICAS was significantly more frequent in subjects
      in the FLD group than those in the non-FLD group (25.0% vs. 5.8%). A logistic
      regression analysis revealed that age and FLD were significant determinants of
      ICAS. CONCLUSION: Our study findings suggest a significant association between
      ICAS and FLD.

PMID- 24930644
TI  - Propensity score-matched lesion-based comparison of mid-term angiographic
      outcomes of TAXUS Liberte with Cypher Bx Velocity stents for de novo native
      coronary stenosis and in patients with diabetes.
AB  - OBJECTIVE: We sought to perform a propensity score-matched lesion-based
      comparison of mid-term angiographic outcomes of sirolimus- (SES, Cypher Bx
      Velocity) and paclitaxel- (PES, TAXUS Liberte, the 2nd-generation TAXUS) eluting
      stents to treat de novo coronary stenosis and, particularly, in patients with
      diabetes mellitus (DM) in a daily practice environment. METHODS: The present
      study was a non-randomized, retrospective, lesion-based, single center study that
      included 1,287 de novo native coronary stenosis cases after successful SES or PES
      placement between February 2007 and April 2011. The primary endpoint was
      angiographic-based binary in-stent restenosis (% diameter stenosis >50 at
      secondary angiogram) within 550 days of placement. A propensity score-matched
      analysis was used to adjust the baselines. RESULTS: Among 360 baseline-adjusted
      angiographic lesions followed up in each arm, the incidence of the primary
      endpoint in the PES group (11.7%, follow-up period: 350+/-76 days) was not
      significantly different from that in the SES group (10.3%, p=0.645, 354+/-81
      days, p=0.912). PES was not associated with the primary endpoint by logistic
      regression analysis (odds ratio: 1.15, 95% confidence interval: 0.68-1.93,
      p=0.605). In the DM specific sub-analysis, the primary endpoint in the PES group
      (19.6%) was not significantly different from that in the SES group (12.8%,
      p=0.105) in 148 baseline-adjusted lesions in each arm. CONCLUSION: The mid-term
      angiographic outcomes after TAXUS Liberte placement for all-comer de novo native
      coronary stenosis and in patients with DM were not significantly different from
      those of SES in a Japanese daily practice environment.

PMID- 24930645
TI  - The prevalence and risk factors of microalbuminuria in hypertensive patients
      under current medical treatment.
AB  - OBJECTIVE: A link between urinary albumin excretion and an increased incidence of
      cardiovascular mortality has already been demonstrated. However, the reported
      prevalence of microalbuminuria (MAU) in patients with hypertension is highly
      variable. We therefore aimed to conduct a cross-sectional multicenter study to
      investigate the prevalence of urinary albumin excretion in treated hypertensive
      patients in our current practice. METHODS: A total of 1,258 hypertensive patients
      were enrolled in this study. Patients with macroalbuminuria were excluded. The
      concentrations of urinary microalbumin and creatinine were measured. Urinary
      albumin excretion was expressed as the ratio of albumin to creatinine excretion.
      RESULTS: The mean systolic and diastolic blood pressures were 130.9+/-12.7 mmHg
      and 74.7+/-8.9 mmHg, respectively. The overall prevalence of MAU was 42.8%, and
      it was observed in 35.8% of patients treated with a single medication. Patients
      with polyvascular disease exhibited a higher prevalence of MAU compared with
      patients with monovascular disease. The factors related to the presence of MAU
      included the estimated glomerular filtration rate (eGFR), systolic blood
      pressure, and glycated hemoglobin (HbA1c) level (odds ratios [ORs] of 0.988,
      1.026, and 1.371, respectively). CONCLUSION: The present study showed that the
      prevalence of MAU among hypertensive patients was 42.8%, even in patients whose
      blood pressure was relatively well controlled. Additionally, the eGFR, systolic
      blood pressure, and HbA1c level are risk factors for the development of MAU.
      These findings suggest that a substantial number of hypertensive patients have
      MAU and highlight the importance of strictly controlling these factors to improve
      patient prognosis.

PMID- 24930646
TI  - Type 2 diabetes mellitus complicated by hypertension in Japanese patients:
      switching treatment from high-dose angiotensin II receptor blockers to losartan
      plus hydrochlorothiazide.
AB  - OBJECTIVE: The aim of the present study was to assess changes in blood pressure
      and metabolism after switching treatment from maximum-dose angiotensin II
      receptor blocker (ARB) therapy to a mixture of conventional-dose ARBs and low
      dose diuretics. METHODS: This study was conducted among 43 Japanese patients with
      type 2 diabetes complicated with hypertension in whom continuous treatment with
      high doses of ARBs did not reduce their blood pressure to the target level (a
      systolic blood pressure of 130 mmHg or lower and a diastolic blood pressure of 80
      mmHg or lower). The antihypertensive and metabolic effects of switching from high
      dose ARBs to a combination of losartan (50 mg/day) plus hydrochlorothiazide (12.5
      mg/day) were examined. The primary endpoint was a decrease in blood pressure at
      24 weeks. RESULTS: The combination treatment significantly decreased both
      systolic (baseline: 147+/-11; 24 weeks: 133+/-13 mmHg) and diastolic (baseline:
      79+/-8; 24 weeks: 72+/-10 mmHg) blood pressure. This treatment was also
      associated with a significant increase in the HbA1c level (baseline: 7.0+/-0.8%;
      24 weeks: 7.2+/-0.9%) and a significant decrease in the urinary albumin
      creatinine ratio (baseline: 280+/-590; 24 weeks: 110+/-253 mg/g creatinine).
      However, the combination treatment had no effect on lipid metabolism or the serum
      uric acid or potassium levels. CONCLUSION: In patients with diabetes, sodium
      reabsorption in the renal tubules is enhanced, which leads to the development of
      salt-sensitive hypertension. Therefore, the concurrent use of a diuretic that
      promotes sodium excretion can increase the antihypertensive effects of other
      drugs. This study demonstrated that switching from high-dose ARB treatment to
      losartan/hydrochlorothiazide combination therapy results in significant control
      of blood pressure.

PMID- 24930647
TI  - Characteristics of tuberculosis in patients with rheumatoid arthritis: a
      retrospective single-center study.
AB  - OBJECTIVE: The objective of this study was to assess the characteristics of
      hospitalized patients suffering from tuberculosis with rheumatoid arthritis (RA),
      focusing specifically on those treated without anti-tumor necrosis factor (TNF)
      therapy. METHODS: We conducted a retrospective review to assess the
      characteristics of 1,022 hospitalized Japanese patients suffering from
      tuberculosis with and without RA between 2002 and 2011. RESULTS: Compared with
      the 995 non-RA patients with tuberculosis, the 24 RA patients with tuberculosis
      treated without anti-TNF therapy were older and predominantly female. They less
      frequently had a history of smoking, with a higher rate of underlying respiratory
      diseases, an impaired performance status and side effects. The three RA patients
      receiving anti-TNF therapy had extrapulmonary tuberculosis; however, the rate of
      extrapulmonary tuberculosis in the other RA patients treated without anti-TNF
      therapy did not differ from that observed in the non-RA patients. Five patients
      died during hospitalization. The in-hospital mortality of the RA patients did not
      differ significantly from that of the non-RA patients. Independent factors
      contributing to in-hospital mortality did not include RA. CONCLUSION: In this
      study, the RA patients treated without anti-TNF therapy did not differ from the
      non-RA patients in terms of the rate of extrapulmonary tuberculosis or bilateral
      pulmonary lesions, although they did exhibit a higher frequency of side effects
      of antituberculosis treatment. RA was not found to be an independent factor
      contributing to in-hospital mortality.

PMID- 24930648
TI  - Clinical features of pulmonary aspergillosis associated with interstitial
      pneumonia.
AB  - OBJECTIVE: We retrospectively investigated the clinical features of pulmonary
      aspergillosis associated with interstitial pneumonia. METHODS: We reviewed the
      medical records of all patients treated for interstitial pneumonia with or
      without pulmonary aspergillosis at our institution between April 2006 and August
      2012 and evaluated the clinical features as well as risk and prognostic factors
      for pulmonary aspergillosis associated with interstitial pneumonia. RESULTS:
      Among 539 patients with interstitial pneumonia, 15 who suffered from pulmonary
      aspergillosis were identified. The median age was 69.2+/-7.0 years, and fourteen
      patients were men. The subtypes of pulmonary aspergillosis were chronic pulmonary
      aspergillosis (n=14) and invasive pulmonary aspergillosis (n=1). The forms of
      interstitial pneumonia included idiopathic pulmonary fibrosis (n=9), rheumatoid
      arthritis-related interstitial pneumonia (n=4) and pleuroparenchymal
      fibroelastosis (n=2). The underlying conditions were emphysema (n=9) and a
      history of oral corticosteroid and/or immunosuppressive use (n=4). Home oxygen
      therapy (HOT) was administered in 11 patients. Following the diagnosis of
      pulmonary aspergillosis, all patients were treated with antifungal drugs. Ten
      patients (66.6%) died. A comparison of the interstitial pneumonia patients with
      and without pulmonary aspergillosis showed that the presence of emphysema, use of
      HOT and death were significantly associated with pulmonary aspergillosis.
      CONCLUSION: Pulmonary aspergillosis is one of the major complications of
      interstitial pneumonia and its prognosis is poor. Therefore, providing careful
      monitoring and proper treatment is extremely important.

PMID- 24930649
TI  - The accuracy and uncertainty of a sheet-type portable monitor as a screening
      device to identify obstructive sleep apnea-hypopnea syndrome.
AB  - OBJECTIVE: Laboratory-based polysomnography (PSG) is the gold standard for
      diagnosing obstructive sleep apnea-hypopnea syndrome (OSAHS), but it is expensive
      and requires overnight hospitalization. Recently, a sheet-shaped breath detection
      monitor, the SD-101, has been developed, and several reports have so far
      demonstrated the screening accuracy of this device. The aim of this study was to
      assess the accuracy and the uncertainty of this device. METHODS: A total of 101
      suspected OSAHS patients underwent simultaneous examinations with PSG and the SD
      101. RESULTS: There was a statistically significant relationship between the
      respiratory disturbance index (RDI) by the SD-101 and the apnea-hypopnea index
      (AHI) by PSG. At an RDI cutoff of 14 episodes per hour, the sensitivity and
      specificity to detect an AHI >=20 episodes per hour were 90.2% and 90.0%,
      respectively. To reduce the influence of sleep efficiency, the time in bed (TIB)
      obtained from PSG, instead of the total seep time (TST), was used to calculate
      the AHI from the PSG data. There was also a statistically significant
      relationship between the RDI and AHI for the TIB. Moreover, it was suggested that
      arousal index and TIB were likely associated with false-negative and/or false
      positive results. CONCLUSION: Although the present study demonstrated a close
      relationship between the RDI and the AHI, use of the SD-101 to examine
      symptomatic OSAHS patients should be performed with a full understanding of its
      incapability to detect the sleep state, including arousal reaction and the
      existence of false respiratory events caused by body movements.

PMID- 24930650
TI  - The use of oral beclomethasone dipropionate in the treatment of gastrointestinal
      graft-versus-host disease: the experience of the Fukuoka blood and marrow
      transplantation (BMT) group.
AB  - OBJECTIVE: We examined the therapeutic strategies for treating mild
      gastrointestinal (GI) graft-versus-host disease (GVHD) using oral beclomethasone
      dipropionate (BDP) in 15 Japanese patients based on the donor source. The primary
      objective was to determine the efficacy and toxicity of oral BDP combined
      with/without low-dose prednisone (PSL). METHODS: Oral BDP was administered with 1
      mg/kg/d of PSL in patients undergoing bone marrow transplantation (BMT) or
      peripheral blood stem cell transplantation (PBSCT; n=11), and the dose of PSL was
      tapered off after 22 days. Oral BDP alone was administered in patients undergoing
      cord blood stem cell transplantation (CBSCT; n=4). The primary endpoint was the
      rate of treatment success on day 49, as measured according to the improvement or
      complete resolution of GI symptoms without additional treatment. The secondary
      endpoints included treatment-related toxicity according to the National Cancer
      Institute Common Toxicity Criteria version 3.0, the rate of treatment
      discontinuation due to toxicity, the rate of relapse of acute GVHD by day 100 and
      the incidence of bacterial, fungal or viral infection, including cytomegalovirus
      (CMV) antigenemia. RESULTS: Treatment success was achieved in seven of the 11
      (64%) patients undergoing BMT or PBSCT and in all four patients (100%) undergoing
      CBSCT. Subsequent adverse events included herpes zoster infection, catheter
      associated sepsis and CMV enteritis; all affected patients responded well to
      treatment. CONCLUSION: The use of a risk-stratified treatment strategy with oral
      BDP depending on the stem cell source is effective in patients with mild GI-GVHD.

PMID- 24930651
TI  - Clinical review of 24 patients with acute cholecystitis after acute cerebral
      infarction.
AB  - OBJECTIVE: Acute cholecystitis (AC) after acute cerebral infarction is rare and
      has not been fully investigated. Because patients with acute cerebral infarction
      often cannot complain of abdominal pain due to loss of consciousness, hemiparesis
      and aphasia, delays in diagnosis may increase the severity of the condition. It
      is clearly important to identify symptoms, reach a diagnosis and provide
      treatment as soon as possible. The purpose of this study was to investigate the
      clinical features of AC after acute cerebral infarction. METHODS: Among the 1,682
      patients with acute cerebral infarction admitted to our hospital between April
      2007 and July 2012, AC after acute cerebral infarction was diagnosed in 24
      (1.4%). Data regarding age, sex, past history, fasting period, period from
      admission to the onset of cholecystitis, clinical type, severity of
      cholecystitis, diffusion-weighted imaging Alberta Stroke Program Early Computed
      Tomography Score, National Institutes of Health Stroke Scale (NIHSS) score at
      onset and modified Rankin scale at 90 days were investigated. RESULTS: The mean
      age of the 24 patients (15 men, 9 women) was 74.2+/-11.9 years (range, 45-90
      years). The clinical type was atherothrombosis in five patients, lacunar
      infarction in seven patients, cardiac embolism in 10 patients and dissection in
      two patients. The past history included atrial fibrillation in 10 (42%) patients,
      hypertension in 20 (83%) patients and diabetes in 11 (46%) patients. The mean
      duration of fasting was 10.7 days (range, 1-32 days). The mean interval between
      the onset of cholecystitis and admission was 8.3 days (range, 0-24 days). The
      median NIHSS score at onset of cerebral infarction was 10, and 23 (96%) patients
      were bedridden at the onset of cholecystitis. CONCLUSION: AC after acute cerebral
      infarction was frequently observed in the patients with severe hemiparesis and
      those who were fasted. It is important to identify symptoms, accurately diagnose
      the condition and provide treatment as soon as possible in order to achieve early
      ambulation and resumption of food intake using a feeding tube.

PMID- 24930652
TI  - Respiratory insufficiency with preserved diaphragmatic function in amyotrophic
      lateral sclerosis.
AB  - OBJECTIVE: We performed a longitudinal study to elucidate the correlation between
      respiratory insufficiency and respiratory biomarkers, including diaphragmatic
      compound muscle action potential (DCMAP), at the initiation of noninvasive
      ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). METHODS:
      The patients were assessed at least every six months. Additional assessments were
      performed at the start of respiratory therapy when the patients met the criteria
      for the initiation of NIV. Each assessment consisted of a full neurological
      examination, a phrenic nerve conduction study, respiratory function tests, and
      nocturnal pulsed oximetry. PATIENTS: We enrolled 43 patients with either definite
      or probable ALS as defined by the revised El Escorial criteria. RESULTS: The
      patients were divided into two groups according to the timing of the initiation
      of respiratory therapy. Seventeen patients (group A) met the criteria for NIV
      initiation when their DCMAP remained normal. Twenty-six patients (group B) met
      the criteria when their DCMAP decreased below normal limits. Although respiratory
      function parameters were significantly worse in group B compared with group A at
      NIV initiation, more than 80% of the patients in both groups developed nocturnal
      desaturation during sleep. CONCLUSION: DCMAP is not always a reliable indicator
      for determining the optimal timing for NIV initiation during the progression of
      respiratory insufficiency in ALS. Physicians should be aware of the risk of
      respiratory insufficiency during sleep in patients with ALS.

PMID- 24930653
TI  - Clinicopathological findings of four cases of pure influenza virus A pneumonia.
AB  - OBJECTIVE: The purpose of this study was to perform clinicopathological
      evaluations of patients with pure influenza A virus pneumonia. METHODS: We
      performed clinicopathological analyses of four cases of pure influenza A virus
      pneumonia. Patients Among the four cases, three were caused by the pandemic
      (H1N1) 2009 virus. Three patients were analyzed during autopsy, and one underwent
      transbronchial lung biopsy. RESULTS: We suggest that the interval between
      influenza virus A pneumonia onset and our analysis affected the pathological
      findings. Diffuse alveolar damage was observed during the acute phase. After ten
      days, organizing pneumonia and marked proliferation of premature type II alveolar
      epithelium were observed. Clinically, intra-alveolar hemorrhage was observed in
      two patients. Pathologically, hyaline membrane formation and intra-alveolar
      hemorrhage were observed in all cases. CONCLUSION: Severe epithelial damage was
      determined as the main mechanism of respiratory failure caused by influenza A
      virus pneumonia.

PMID- 24930654
TI  - An HBV-HIV co-infected patient treated with tenofovir-based therapy who achieved
      HBs antigen/antibody seroconversion.
AB  - The present report describes a case of a patient with hepatitis B virus (HBV)
      human immunodeficiency virus (HIV) co-infection who was treated with tenofovir
      disoproxil (TDF)-based highly active antiretroviral therapy (HAART) and who
      achieved HBs antigen (Ag)/antibody (Ab) seroconversion. An 18-year-old Japanese
      man with HIV and HBV co-infection presented to our hospital. His CD4 count was
      decreased, and TDF-based HARRT was started. At 30 months after initiation of
      therapy, HBsAg was not detected. At 36 months after initiation of therapy, HBsAb
      was detected. We conclude that TDF-based therapy is useful for the management of
      patients with HBV and HIV co-infection. 

PMID- 24930655
TI  - Syncope due to paroxysmal complete atrioventricular block in a patient with
      aortic valve stenosis.
AB  - A 66-year-old man was admitted due to repeated syncope, and the electrocardiogram
      showed complete atrioventricular block (CAVB). He had moderate aortic valve
      stenosis (AS) with a severely calcified valve. This case indicates that if
      calcification spreads into the cardiac conduction system, it may cause CAVB.
      Although CAVB is not typically considered a main cause of syncope in AS patients,
      it should nevertheless be considered in the differential diagnosis. 

PMID- 24930656
TI  - Saxagliptin-induced recurrent acute pancreatitis.
AB  - Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been implicated in the
      development of acute pancreatitis, the causality of this phenomenon is not well
      established. We herein report the case of an 85-year-old woman who presented with
      epigastric pain after taking saxagliptin for five months. A high serum lipase
      level with characteristic computed tomography findings confirmed the diagnosis of
      acute pancreatitis. The patient's symptoms rapidly resolved after admission,
      although they recurred when she resumed treatment with saxagliptin for 18 days
      after discharge. In the absence of any identifiable causes of pancreatitis and
      considering the temporal sequence of events, the saxagliptin therapy was highly
      suspected to be the triggering factor. Although drug-induced pancreatitis is
      rare, treatment with DPP-4 inhibitors should be included as a potential etiology
      of acute pancreatitis. 

PMID- 24930657
TI  - Hepatic cyst infection in an autosomal dominant polycystic kidney disease patient
      diagnosed by right pleural effusion.
AB  - A 64-year-old Japanese man with renal dysfunction caused by autosomal dominant
      polycystic kidney disease (ADPKD) was admitted to our hospital for evaluation of
      right back pain, fever, inflammation, and pleural effusion. Diagnostic
      investigations for tuberculous pleuritis were all negative. Although no
      radiographic abnormality suggesting hepatic cyst infection was detected by
      computed tomography, hepatic cyst drainage demonstrated purulent contents
      indicative of cyst infection. Conglutination of the cyst by minocycline 100 mg
      was performed five times in addition to drainage. After drainage, the symptoms of
      inflammation, right back pain and right pleural effusion subsided. Renal function
      and anemia, which had been resistant to darbepoetin treatment, also improved
      after the procedure. These results suggested that the infected hepatic cyst was
      associated with the patient's symptoms, exacerbation of renal dysfunction and
      anemia. The pleural effusion was due to the propagation of inflammation from the
      cyst infection. This is the first report of an infected hepatic cyst in an ADPKD
      patient presenting with and diagnosed by right pleural effusion. 

PMID- 24930658
TI  - Pulmonary Mycobacterium fortuitum infection with cervical lymphadenitis in a
      patient carrying autoantibodies to interferon-gamma.
AB  - A 74-year-old woman was referred to our hospital for an evaluation of
      unidentified pneumonia. She gradually developed a high-grade fever with a growing
      infiltrative shadow on chest CT and an enlarging bilateral cervical mass. She was
      diagnosed with a pulmonary Mycobacterium fortuitum (M. fortuitum) infection with
      cervical lymphadenitis based on the results of an open biopsy of the cervical
      lymph node. While the patient's clinical condition resolved almost completely
      after treatment with multiple antibiotics, neutralizing autoantibodies to
      interferon-gamma (IFN-gamma) were identified in her serum. The progression of
      disseminated M. fortuitum infection in immunocompetent patients may be affected
      by the presence of autoantibodies to IFN-gamma. 

PMID- 24930659
TI  - Multiple deletions in mitochondrial DNA in a patient with progressive external
      ophthalmoplegia, leukoencephalopathy and hypogonadism.
AB  - Progressive external ophthalmoplegia (PEO) is one of a number of major types of
      mitochondrial disorders. Most sporadic PEO patients have a heteroplasmic large
      deletion of mitochondrial DNA (mtDNA) in the mitochondria in skeletal muscles. We
      herein analyzed mtDNA deletions using sub-cloning and Sanger sequencing of PCR
      products in a 31-year-old Japanese man with multiple symptoms, including PEO,
      muscle weakness, hearing loss, leukoencephalopathy and hypogonadism. A large
      number of multiple deletions was detected, as well as four kinds of deletion
      breakpoints identified in different locations, including m.3347_12322,
      m.5818_13964, m.5829_13964 and m.5837_13503. 

PMID- 24930660
TI  - An autopsy case involving a 12-year history of amyotrophic lateral sclerosis with
      CIDP-like polyneuropathy.
AB  - Demyelinating polyneuropathy associated with amyotrophic lateral sclerosis (ALS)
      is quite rare. We herein present the case of a woman patient with a 12-year
      history of chronic inflammatory demyelinating polyneuropathy (CIDP)-like
      polyneuropathy who later developed bulbar palsy and respiratory failure. The
      autopsy findings revealed neuronal loss in the anterior horn and primary motor
      cortex with degeneration of the corticospinal tracts. Diffuse phosphorylated TAR
      DNA-binding protein of 43 kDa inclusions were observed in the anterior horn and
      cerebral cortices, including the temporal lobe. The final diagnosis was ALS with
      CIDP-like polyneuropathy. Compared with other reports of ALS with CIDP-like
      polyneuropathy, the present patient was younger and followed a relatively long
      clinical course, with no upper motor neuron signs. 

PMID- 24930661
TI  - Hereditary diffuse leukoencephalopathy with spheroids characterized by spastic
      hemiplegia preceding mental impairment.
AB  - Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a young-adult
      onset autosomal dominant white matter disease characterized by progressive
      cognitive dysfunction. We herein report the case of a 20-year-old woman who
      developed spastic hemiplegia. Brain magnetic resonance imaging revealed increased
      bilateral T2 signal intensity and bright diffusion-weighted imaging signals with
      a low apparent diffusion coefficient within the frontoparietal white matter. The
      lesion gradually expanded for over one year. The patient was initially diagnosed
      with multiple sclerosis (MS); however, she did not respond to immunosuppressive
      therapy. DNA sequencing showed a heterozygous c.2381T>C mutation in colony
      stimulating factor 1 receptor. HDLS with a pure motor phenotype is sometimes
      difficult to differentiate from MS. 

PMID- 24930662
TI  - Cerebral infarction associated with accessory middle cerebral arteries: two case
      reports.
AB  - We herein present two cases of cerebral infarction in the middle cerebral artery
      (MCA) territory associated with an accessory middle cerebral artery (AMCA), which
      is a rare anomalous vessel arising from the anterior cerebral artery that
      coexists with the main trunk of the MCA. Cerebral infarction occurred in both
      patients: due to occlusion of the MCA main trunk in one patient and occlusion of
      the AMCA in the other patient. These cases suggest the importance of recognizing
      an AMCA when interpreting neuroradiological findings in patients with MCA
      ischemic stroke, especially in the hyperacute phase. 

PMID- 24930663
TI  - Concurrent subcutaneous candidal abscesses and pulmonary cryptococcosis in a
      patient with diabetes mellitus and a history of corticosteroid therapy.
AB  - A 50-year-old man with a history of long-term corticosteroid treatment following
      adrenalectomy for Cushing's syndrome and uncontrolled diabetes mellitus was
      admitted for an examination of an abnormal thoracic shadow. Cryptococcal serum
      antigens were positive, and the histopathology of a lung biopsy showed
      encapsulated yeast resembling Cryptococcus neoformans. On admission, the serum
      beta-D-glucan level was approximately twice the cutoff value, several nodules
      were observed on both legs and magnetic resonance imaging revealed subcutaneous
      abscesses. Candida albicans was identified from needle aspirates, and the patient
      was successfully treated with fluconazole and flucytosine. We herein report the
      first case of concurrent C. albicans skin abscesses and pulmonary cryptococcosis.

PMID- 24930664
TI  - Pulmonary Nocardia nova infection after allogeneic hematopoietic stem cell
      transplantation.
AB  - We herein report the case of a 68-year-old man with a history of allogeneic
      hematopoietic stem cell transplantation for acute myelocytic leukemia in whom
      graft-versus-host disease (GVHD) developed in the gastrointestinal tract and
      liver five months after transplantation. In that same period, chest computed
      tomography showed infiltration in both upper lungs. We performed bronchoscopy to
      clarify the GVHD and pulmonary infection. Nocardia nova was identified in the
      bronchoalveolar lavage fluid, and we diagnosed the patient as having pulmonary
      nocardiosis. Because the differential diagnosis is important for the medical
      management of GVHD and pulmonary infection, performing bronchoscopy is essential
      for making an appropriate and rapid diagnosis. 

PMID- 24930665
TI  - Regression of duodenal follicular lymphoma: susceptible to H. pylori eradication?

PMID- 24930666
TI  - New epidemiology of Staphylococcus aureus infections.

PMID- 24930667
TI  - The mechanism of selective molecular capture in carbon nanotube networks.
AB  - Recently, air pollution issues have drawn significant attention to the
      development of efficient air filters, and one of the most promising materials for
      this purpose is nanofibers. We explore here the mechanism of selective molecular
      capture of volatile organic compounds in carbon nanotube networks by performing
      atomistic simulations. The results are discussed with respect to the two key
      parameters that define the performance of nanofiltration, i.e. the capture
      efficiency and flow resistance, which demonstrate the advantages of carbon
      nanotube networks with high surface-to-volume ratio and atomistically smooth
      surfaces. We also reveal the important roles of interfacial adhesion and
      diffusion that govern selective gas transport through the network. 

PMID- 24930668
TI  - Density functional theory and its applications.

PMID- 24930670
TI  - Honorary and ghost authorship in nursing publications.
AB  - PURPOSE: The purposes of this study were to (a) assess the prevalence of articles
      with honorary authors and ghost authors in 10 leading peer-reviewed nursing
      journals between 2010 to 2012; (b) compare the results to prevalence reported by
      authors of articles published in high-impact medical journals; and (c) assess the
      experiences of editors in the International Academy of Nursing Editors with
      honorary and guest authorship. METHODS: Corresponding authors of articles
      published in 10 nursing journals between 2010 and 2012 were invited to complete
      an online survey about the contributions of coauthors to see if the International
      Committee of Medical Journal Editors () criteria for authorship were met.
      Additionally, members of the International Academy of Nursing Editors were
      invited to complete an online survey about their experiences in identifying
      honorary or ghost authors in articles submitted for publication. FINDINGS: The
      prevalence of articles published in 10 nursing journals with honorary authors was
      42%, and the prevalence of ghost authorship was 27.6%. This is a greater
      prevalence than what has been reported among medical journals. Qualitative data
      yielded five themes: lack of awareness around the rules for authorship;
      acknowledged need for debate, discussion, and promotion of ethical practice;
      knowingly tolerating, and sometimes deliberately promoting, transgressions in
      practice; power relations and expectations; and avoiding scrutiny. Among the 60
      respondents to the editor survey, 22 (36.7%) reported identifying honorary
      authors and 13 (21.7%) reported ghost authors among papers submitted to their
      publications. CONCLUSIONS: Inappropriate authorship is a significant problem
      among scholarly nursing publications. RELEVANCE: If nursing scholarship is to
      maintain integrity and be considered trustworthy, and if publications are to be a
      factor in professional advancement, editors, nursing leaders, and faculty need to
      disseminate and adhere to ethical authorship practices.

PMID- 24930669
TI  - Expression level of hTERT is regulated by somatic mutation and common single
      nucleotide polymorphism at promoter region in glioblastoma.
AB  - We investigated the role of somatic mutations and a common single nucleotide
      polymorphism (SNP) in the hTERT promoter region on hTERT expression and clinical
      outcomes. The hTERT promoter region was sequenced from 48 glioblastomas. hTERT
      expression was analyzed by quantitative real time-PCR. The association between
      hTERT promoter genetic changes and other genomic events and clinical variables
      common in gliomas were examined. C228T and C250T somatic mutations were found in
      60.4% of glioblastomas, and a common SNP (T349C) was found in 66.6%. Somatic
      mutations and the SNP likely have opposing effects on hTERT expression. hTERT
      expression was significantly higher in the C228T or C250T mutated tumors. Tumors
      with the T349C genotype showed lower hTERT expression when C228T or C250T
      mutations were present. However, no significant survival differences were
      observed among the groups with or without hTERT promoter mutations and SNP. There
      was a significant association between genetic changes in the hTERT promoter and
      patient age as well as MGMT promoter methylation and EGFR amplification. hTERT
      expression is modulated by somatic mutations in the hTERT promoter as well as a
      common polymorphism. However, hTERT related genomic changes have limited value as
      an independent prognostic factor for clinical outcomes in glioblastomas. 

PMID- 24930671
TI  - Development and application of a quantitative fluorescence-based
      immunochromatographic assay for fumonisin b1 in maize.
AB  - A fluorescence-based immunochromatographic assay (ICA) for fumonisin B1 (FB1)
      that employs conjugates of fluorescent microspheres and monoclonal antibodies (FM
      mAbs) as detection reporters is described. The ICA is based on the competitive
      reaction between FB1-bovine serum albumin (BSA; test line) and the target FB1 for
      binding to the FM-mAb conjugates. A limit of detection (LOD) for FB1 of 0.12
      ng/mL was obtained, with an analytical working range of 0.25-2.0 ng/mL
      (corresponding to 250-2000 MUg/kg in maize flour samples, according to the
      extraction procedure). The recoveries of the ICA to detect FB1 in maize samples
      ranged from 91.4 to 118.2%. A quantitative comparison of the fluorescence-based
      ICA and HPLC-MS/MS analysis of naturally contaminated maize samples indicated
      good agreement between the two methods (r(2) = 0.93). By replacing the target of
      interest, the FM-based ICA can easily be extended to other chemical contaminants
      and thus represents a versatile strategy for food safety analysis. 

PMID- 24930672
TI  - Tunneling spectroscopy measurements on hydrogen-bonded supramolecular polymers.
AB  - We studied the formation of hydrogen-bonded supramolecular polymers of Ethyl
      Hexyl Urea Toluene (EHUT) on a gold (111) surface by low temperature scanning
      tunneling microscopy. Tunneling spectroscopy performed along an individual
      molecule embedded in a self-assembled layer revealed strong changes in the value
      of the HOMO-LUMO gap. A variation of the LUMO state is attributed to the effect
      of space charge accumulation resulting from anisotropic adhesion of the molecule.
      In addition, for specific tunneling conditions, changes induced through the
      formation of hydrogen bonds became visible in the differential conductance
      (dI/dV) maps; isolated molecules, hydrogen bonded dimers and supramolecular
      polymers of EHUT were distinguishable through their electronic properties. 

PMID- 24930673
TI  - Large Pseudoaneurysm of the mitral annulus as an infective endocarditis
      complication: a 3D echocardiography role in diagnosis and surgical procedure.

PMID- 24930674
TI  - Frequent amplification of ORAOV1 gene in esophageal squamous cell cancer promotes
      an aggressive phenotype via proline metabolism and ROS production.
AB  - Chromosomal band 11q13 seems to be one of the most frequently amplified lesions
      in human cancer, including esophageal squamous cell cancer (ESCC). The oral
      cancer overexpressed 1 (ORAOV1) gene has been identified within this region, but
      its detailed biological function in human ESCC remains largely unclear. In our
      clinical samples of stage III ESCC, ORAOV1 amplification was observed in 49 of 94
      cases (53%). ORAOV1 amplification was significantly associated with a poorly
      differentiated histology and tumors located in the upper or middle esophagus.
      Patients with ORAOV1 amplification tended to have a shorter survival period,
      although the difference was not significant. To investigate the function of
      ORAOV1, we created ORAOV1--overexpressed ESCC cell lines that exhibited increased
      cellular proliferation and colony formation, compared with in vitro controls. In
      vivo, ORAOV1-overexpressed cells exhibited a significantly increased
      tumorigenicity and a significantly larger tumor volume and poorer differentiation
      than controls. The peptide mass fingerprinting technique demonstrated that ORAOV1
      bound to pyrroline-5-carboxylate reductase (PYCR), which is associated with
      proline metabolism and reactive oxygen species (ROS) production. Then, ORAOV1
      overexpressed cell lines were resistant to stress treatment, which was cancelled
      by PYCR-knockdown. In addition, the ORAOV1-overexpressed cell line had a higher
      intracellular proline concentration and a lower ROS level. Our findings indicate
      that the ORAOV1 gene is frequently amplified in ESCC, enhances tumorigenicity and
      tumor growth, and is associated with a poorly differentiated tumor histology via
      proline metabolism and ROS production. ORAOV1 could be a novel target for the
      treatment of ESCC. 

PMID- 24930675
TI  - The role of opioid processes in reward and decision-making.
AB  - Contemporary theories emphasize the involvement of the endogenous opioid system
      in assigning hedonic values to rewards. Although earlier research supports this
      view, recent findings suggest that opioids play a larger and more complex role in
      reward processes than these theories suggest. For example, opioid activity in the
      basolateral amygdala is required for encoding incentive learning, a process by
      which the value of goal-directed actions is updated. Outside the amygdala, opioid
      receptors in the ventral striatum have been found to promote choice between
      different courses of action. Specifically, MU opioid receptors in the nucleus
      accumbens core and delta opioid receptors in the nucleus accumbens shell have
      been reported to mediate distinct aspects of incentive motivation; the core
      regulating the effect of experienced reward and the shell of predicted reward on
      choice. In both cases, the involvement of opioid receptors was restricted to the
      time of choice, although changes in their expression pattern could be observed
      prior to that point. This time-restricted involvement of opioid receptor-related
      processes is consistent with the view that opioids in the nucleus accumbens are
      central components of the limbic-motor interface, integrating reward-related
      information with instrumental learning to guide decision-making, particularly the
      selection and execution of goal-directed actions. LINKED ARTICLES: This article
      is part of a themed section on Opioids: New Pathways to Functional Selectivity.
      To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24930676
TI  - An overview of visceral leishmaniasis elimination program in India: a picture
      imperfect.
AB  - Visceral leishmaniasis (VL) has been one of the most neglected tropical diseases
      in India. Concurrent and correct data on the burden of VL is vital to plan,
      allocate trained resources and to monitor the progress of the elimination
      program. More emphasis on integrated vector management can help in combating the
      disease spread. Effective surveillance, active and accurate diagnosis using rK39
      strip test and use of an affordable, safe and efficient treatment option like
      liposomal amphotericin B remain the key components of VL control. Sustained
      advocacy, information, education and communication are needed in all the endemic
      areas. In this paper, we review the effectiveness of the strategies adopted in VL
      elimination in India. 

PMID- 24930678
TI  - Sleep dysfunction and its management in Parkinson's disease.
AB  - OPINION STATEMENT: Sleep disorders are among the most common non-motor symptoms
      in Parkinson's Disease (PD). In some cases, symptoms can precede a diagnosis of
      PD by many years, but otherwise they are commonly encountered during the clinical
      care of patients. Unfortunately, sleep problems are under-recognized and
      subsequently inadequately addressed. In our experience, when properly addressed,
      physicians and patients are quickly aware of the often-debilitating nature of
      sleep dysfunction. This does not mean that solutions are easily attainable. Sleep
      in PD is held in a delicate balance, influenced by the disease process,
      medications, co-morbid symptoms, and a variety of other factors. For this reason,
      management of sleep in PD often requires an inter-disciplinary approach.
      Physicians should have an intimate knowledge of the many sleep problems apparent
      in PD, as well as appreciate the challenge presented by diverse therapeutic
      options that can both ameliorate and aggravate symptoms.

PMID- 24930679
TI  - Improved glucose tolerance in insulin-resistant rats after pea hull feeding is
      associated with changes in lipid metabolism-targeted transcriptome.
AB  - Understanding of the mechanisms by which pulse grain fractions elicit beneficial
      effects on glucose tolerance is incomplete. An untargeted metabolomic analysis of
      serum from insulin-resistant rats was carried out to identify potential metabolic
      pathways affected by feeding rats the hull fraction of dried peas for 4 weeks.
      From this, we hypothesized that transcription of hepatic genes involved in lipid
      metabolism would be altered. cDNA was prepared from total RNA extracted from
      livers of rats fed a high-fat diet (HFD) or HFD + pea hulls (PH) diet. The liver
      lipid transcriptome of each cDNA sample was characterized using a PCR-based array
      of 84 genes. The activity of peroxisome-proliferator-activated receptor alpha
      (PPAR-alpha) was measured in hepatocyte nuclei. The predominant findings of the
      metabolomic analysis revealed a significant increase in the intermediaries of
      beta-oxidation: C16-OH and C16:1 acylcarnitines (>50%, p < 0.05) and 3
      hydroxybutyrate (100%, p < 0.05) in the PH group compared with the HFD group.
      mRNA of hadha, a gene involved in beta-oxidation, was significantly reduced by
      53% (p < 0.005) in the PH group compared with the HFD group, but no differences
      in PPAR-alpha activity were detected. 3-Hydroxybutyrate concentrations were
      associated with insulin sensitivity and reduced demand for insulin. The results
      indicate that feeding PH alters lipid metabolism in liver, which may contribute
      to improved glucose tolerance in insulin-resistant rats. 

PMID- 24930681
TI  - Understanding the pharmacogenetics of selective serotonin reuptake inhibitors.
AB  - INTRODUCTION: The genetic background of antidepressant response represents a
      unique opportunity to identify biological markers of treatment outcome.
      Encouraging results alternating with inconsistent findings made antidepressant
      pharmacogenetics a stimulating but often discouraging field that requires careful
      discussion about cumulative evidence and methodological issues. AREAS COVERED:
      The present review discusses both known and less replicated genes that have been
      implicated in selective serotonin reuptake inhibitors (SSRIs) efficacy and side
      effects. Candidate genes studies and genome-wide association studies (GWAS) were
      collected through MEDLINE database search (articles published till January 2014).
      Further, GWAS signals localized in promising genetic regions according to
      candidate gene studies are reported in order to assess the general comparability
      of results obtained through these two types of pharmacogenetic studies. Finally,
      a pathway enrichment approach is applied to the top genes (those harboring SNPs
      with p < 0.0001) outlined by previous GWAS in order to identify possible
      molecular mechanisms involved in SSRI effect. EXPERT OPINION: In order to improve
      the understanding of SSRI pharmacogenetics, the present review discusses the
      proposal of moving from the analysis of individual polymorphisms to genes and
      molecular pathways, and from the separation across different methodological
      approaches to their combination. Efforts in this direction are justified by the
      recent evidence of a favorable cost-utility of gene-guided antidepressant
      treatment.

PMID- 24930682
TI  - Selectivity of SSRIs: individualising patient care through rational treatment
      choices.
AB  - Despite a common mode of action [inhibition of the 5-hydroxytryptamine (5-HT)
      neuronal reuptake transporter], proven antidepressant efficacy and a similar
      range of indications (depression and a variety of anxiety disorders), the unique
      secondary binding properties of each selective serotonin reuptake inhibitor
      (SSRI) account for clinically significant differences in tolerability and side
      effect profiles, particularly in some patients. Secondary properties within the
      class of SSRIs include some combination of actions at noradrenergic,
      dopaminergic, muscarinic cholinergic, histaminergic and sigma receptors. In
      addition, most SSRIs inhibit at least one of the cytochrome P450 enzymes,
      resulting in potential pharmacokinetic interactions with co-prescribed drugs.
      Although secondary properties of SSRIs can be associated with side effects,
      sometimes these same actions can be harnessed to good therapeutic effect through
      rational, informed treatment choices. In this way, agents that more consistently
      cause central nervous system activation (such as fluoxetine and sertraline) can
      be used to boost energy in patients whose depression is accompanied by fatigue
      and apathy, while the anxiolytic, sedative properties of others (particularly
      paroxetine and fluvoxamine) can be beneficial in patients with insomnia and
      agitation. When secondary properties are experienced as undesirable side effects,
      agents with greater selectivity for the serotonin transporter and without
      significant secondary binding properties, such as citalopram and escitalopram,
      may be desirable. This article explains how an understanding of the secondary
      binding properties of the SSRIs can guide individualised treatment across the
      spectrum of depressive and anxious states. 

PMID- 24930680
TI  - Insula white matter volume linked to binge drinking frequency through enhancement
      motives in treated adolescents.
AB  - BACKGROUND: Given the insula's role in the representation of bodily states
      associated with hedonic (i.e., enhancement motives) and aversive (i.e., craving)
      aspects of substance use, this longitudinal study examined associations between
      insula structure (i.e., white matter [WM] and gray matter [GM] volume),
      enhancement motives for alcohol and cannabis use, craving for alcohol and
      marijuana, and alcohol and cannabis involvement in treated adolescents.
      Enhancement motives and craving, as conscious representations of bodily states
      associated with use, were hypothesized as mediators (i.e., linking mechanisms) of
      the association between insula volume and substance use. METHODS: Adolescents
      (age 14 to 18, N = 30) recruited from substance use treatment reported on
      enhancement motives and obsession/craving for both alcohol and cannabis at
      baseline (near the start of treatment), and on alcohol and cannabis involvement
      (e.g., binge drinking, alcohol abuse/dependence symptom count) at baseline and
      over 1-year follow-up. Insula WM and GM volumes were determined using FreeSurfer.
      RESULTS: Enhancement motives for drinking served as a link between left insula WM
      volume and frequency of binge drinking at baseline and 1-year follow-up. This
      novel finding is consistent with the insula's role in representing bodily states
      (e.g., "high" associated with binge drinking) that can motivate drinking
      behavior. Although right insula WM volume was positively correlated with
      obsession/craving for alcohol, and obsession/craving was positively correlated
      with alcohol outcomes, the indirect effect was not significant. Insula WM volume
      was not associated with cannabis-related variables. Insula GM volume was not
      associated with enhancement motives, obsession/craving, or alcohol involvement.
      CONCLUSIONS: Enhancement motives for alcohol use, but not obsession/craving for
      alcohol, provided an important link between left insula WM volume and frequency
      of binge drinking in treated adolescents. Results are consistent with the
      insula's role in the processing of hedonic bodily states available to conscious
      awareness, particularly in the form of enhancement motives for alcohol use.

PMID- 24930683
TI  - Escitalopram: a unique mechanism of action.
AB  - The 5-HT (5-hydroxytryptamine, serotonin) transporter (SERT) mediates the
      reuptake of 5-HT from the synaptic cleft into the neuron, and inhibition of this
      uptake is the target of selective serotonin reuptake inhibitors (SSRIs).
      Escitalopram (S-citalopram) is the most selective SSRI available, whereas the
      other enantiomer, R-citalopram, is approximately 30-40 times less potent than the
      S-enantiomer. Both biochemical experiments (measurement of extracellular 5-HT in
      the frontal cortex of rats) and behavioural studies (using the chronic mild
      stress and conditioned fear stress models) demonstrate that R-citalopram appears
      to counteract the effect of escitalopram, and that it is a dose-dependent action.
      When escitalopram is administered at a specific dose, it produces a greater
      effect than when the same dose of the S-enantiomer is administered in combination
      with the R-enantiomer, i.e. when citalopram is administered. While mainly the S
      enantiomer is bound to the primary binding site on the SERT, both enantiomers
      bind to the allosteric binding site. However, the R-enantiomer stabilises the
      binding of the S-enantiomer at the primary site less than the S-enantiomer.
      Furthermore, R-citalopram has an inhibitory effect on the association of
      escitalopram with the transporter, thereby possibly reducing escitalopram's
      effect. In summary, escitalopram appears to possess a unique mechanism of action
      at the 5-HT transporter protein. Furthermore, escitalopram (S-citalopram) is
      different from citalopram because R-citalopram counteracts the activity of the S
      enantiomer. 

PMID- 24930684
TI  - Unique mechanism of action for escitalopram: does it hold the promise?
AB  - There is an unmet need for improved management of depression. Clinicians, as well
      as patients, want medications that are easy to use and have a fast symptom
      relief, consistent efficacy with sustained response and remission combined with a
      good tolerability profile. Studies with escitalopram, a selective serotonin
      reuptake inhibitor with a unique mechanism of action, have shown an early
      response and good remission rates, in comparison with placebo and citalopram. In
      comparison with venlafaxine, a serotonin noradrenaline reuptake inhibitor,
      escitalopram has shown comparable efficacy and earlier response in improving
      depressive symptoms combined with fewer side effects. Results like these, with
      focus on response and remission, are becoming more important, primarily because
      they have greater meaning for the patient in the clinical setting, than scoring
      measures of depression. 

PMID- 24930685
TI  - Anxiety and depression: individual entities or two sides of the same coin?
AB  - Several factors have led to suggestions that anxiety and depression are actually
      the same disease: very frequently, they co-exist; there is an overlap of symptoms
      between the two conditions; a number of similar agents can be used to treat both
      mental states; the same neurotransmitters are involved in both anxiety and
      depressive disorders; and stress can predispose both. Selective serotonin
      reuptake inhibitors (SSRIs) have shown efficacy in a number of neuroses:
      depression; obsessive-compulsive disorder (OCD) and anxiety disorders (panic
      disorder [PD], social anxiety disorder [SAD], generalised anxiety disorder and
      post-traumatic stress disorder). Furthermore, other drugs, for example, tricyclic
      antidepressants and monoamine oxidase inhibitors, are effective in treating both
      depression and some anxiety disorders. Yet some drugs are only effective in
      anxiety, for example, benzodiazepines, and this suggests that the two states are
      actually different. Despite the broad range of conditions that are treated by
      SSRIs, a number of differences are clear when SSRIs are used in depressive and
      anxious states. When used in PD and OCD, the effective dose of the SSRI is often
      higher than when used to treat depression. Furthermore, SSRIs often work more
      slowly in patients with anxiety compared with those with depression. In order to
      assess which serotonergic pathways and mechanisms are involved in these
      conditions, tryptophan depletion tests can be performed. Tryptophan is the
      precursor to serotonin (5-HT), so if the SSRI treatment effects are dependent on
      an increase in synaptic 5-HT levels, depletion will result in a relapse in
      symptoms. However, if the SSRI treatment works through post-receptor events, then
      tryptophan depletion will have little effect on the individual's symptoms. In
      depression, tryptophan depletion induced relapse in patients treated and
      controlled on SSRIs, but not in those recovered on noradrenergic agents such as
      desipramine. In some anxious states (PD and SAD), our work has shown that relapse
      was also experienced following tryptophan depletion, indicating that the SSRIs
      are acting via increasing 5-HT levels at the synapse in these conditions.
      However, other studies have found no effect of the tryptophan depletion test.
      This suggests that in OCD, SSRIs act post-synaptically and therefore have a
      different mechanism of action in OCD patients compared with depressed patients.
      In summary, although most SSRIs are effective in the treatment of both depression
      and anxiety, differences in dose, time to onset of action and, in some cases,
      mechanism of action are evident when treating the two conditions. 

PMID- 24930686
TI  - Priorities in treating depression only.
AB  - Physicians treating depression are, on the whole, not entirely satisfied with
      current antidepressant treatment options. There is a demand for improved
      therapies with a rapid symptom relief, a high remission rate and greater
      prevention of recurrence. The remission rate is particularly important since
      patients with depression not reaching remission have much poorer outcomes than
      those who do. Several studies have shown that the selective serotonin reuptake
      inhibitors (SSRIs) and the serotonin and noradrenergic reuptake inhibitors
      (SNRIs) have higher remission rates than other antidepressant medications.
      However, data from meta-analyses have suggested that venlafaxine shows higher
      remission rates than the SSRIs, fluoxetine, fluvoxamine and paroxetine. It is
      therefore important to examine how the more recently developed SSRIs compare with
      others in the same drug class and also with SNRIs with regard to symptom relief,
      remission rate and tolerability. Using data from three pooled studies, the new
      SSRI escitalopram was compared with the older SSRI citalopram. Escitalopram
      performed significantly better than citalopram and placebo in terms of percentage
      responders (defined as a >=50% decrease of baseline Montgomery and Asberg
      Depression Rating Scale [MADRS] score). Furthermore, in a flexible-dose study the
      remission rate with escitalopram treatment was higher than citalopram during 8
      weeks. Remission (defined as MADRS <=12 at endpoint) in a flexible-dose study was
      also investigated with escitalopram versus extended release venlafaxine. Overall,
      the remission rates were similar between the two medications at the end of week
      8, but patients on escitalopram achieved sustained remission nearly a week
      earlier than those on venlafaxine. Higher remission rates were also found with
      escitalopram compared with venlafaxine in severely ill patients. Furthermore,
      escitalopram also offered important advantages over venlafaxine with regards to
      tolerability. 

PMID- 24930687
TI  - Anxiety disorders: does one treatment fit all?
AB  - Anxiety disorders are relatively common; almost 30% of the population suffer from
      some form of anxiety disorder at some point during their life. Anxiety and
      depressive symptoms often co-exist, and for physicians in primary care the
      boundaries between depression and anxiety disorders (e.g. generalised anxiety
      disorder [GAD], social anxiety disorder [SAD], and panic disorder) are often
      fairly fluid. Differences in treatment tend to occur in patients diagnosed with a
      pure anxiety disorder and those with comorbid anxiety and depression. For
      example, the proportion of patients with pure GAD who seek help and get treated
      for anxiety is much lower than those patients with GAD and comorbid depression.
      The selective serotonin reuptake inhibitor (SSRI) escitalopram is effective in
      panic disorder, reducing panic attack frequency and anticipatory anxiety compared
      with placebo. Furthermore, escitalopram has shown efficacy in patients with SAD
      and GAD. Antidepressants have potential in treating anxiety disorders, and
      further novel drug treatments and development of treatment guidelines will be
      required to effectively manage those patients. 

PMID- 24930688
TI  - Treatment options for real-life patients.
AB  - Our current models of depression and clinical trials data provide inadequate and
      relatively meaningless clinical information. They do not take into account the
      multiple phenotypes of depression and often do not include patients with "real
      life" clinical depression. Psychiatry is called an evidence-based specialty, and
      this is supported by the wealth of evidence provided by the antidepressant drug
      trials. However, if the evidence demonstrated by these trials is not accurate,
      then psychiatry may fail to provide satisfactory treatment for patients with
      depression. Trial data commonly show the effect of antidepressant treatment to be
      indistinguishable from placebo. On first examination it could be said that
      antidepressant drugs act mainly as placebos, or, even worse, that antidepressant
      drugs are no better than placebos in effect. However, this view is at odds with
      the observations of clinicians in everyday practice, and the impact of this
      perception is worrying, with the pharmaceutical companies, patients and
      practitioners all being adversely affected. Randomised controlled trials (RCTs)
      provide limited data about the true effectiveness of an antidepressant. However,
      such RCTs are required by regulatory authorities for drug approval.
      Antidepressant effects in "real-life" depression need further investigation. When
      efficacy data for drug and non-drug treatments for major depression are compared,
      there are very few differences. This lack of differentiation across treatments
      allows every therapy to be perceived as efficacious, but also non-specific. This
      leads to patients being fitted to their therapist's preferred treatment, and not
      vice versa. This "all roads lead to rome" model is contrary to the rest of
      medicine, where differential treatment effects are to be expected. Why,
      therefore, is there confusion? A dimensional model for depression homogenises the
      multiple underlying subtypes of depression. This leads to treatments being tested
      as having universal application instead of targeting the specific depressive
      subtypes. This largely underpins the lack of specificity in RCT evidence. These
      trials involve patients who bear little resemblance to those who clinicians see
      in everyday practice. These trials also select and favour natural and rapid
      responders. Therefore the failure to differentiate between drug and placebo is
      unsurprising in the RCTs. Our spectrum model seeks to identify clinically
      meaningful expressions of depression, allowing drugs to be targeted to separate
      depressive conditions and their underlying cause. This allows a rational model
      for prevention and long-term management. For example, when treating depression
      associated with anxiety, selective serotonin reuptake inhibitors (SSRIs) produce
      a high response in patients with internalised anxious worrying or externalised
      irritability. Not only do they treat the depression but also the fundamental
      cause. In summary, efficacy data will continue to provide little meaningful
      clinical information while treatments are tested as "universal" in reference to
      non-specific conditions such as "major depression". Through use of the spectrum
      model, therapy can be better fitted to depression subtype, through identification
      of clinical phenotypes and their causes. 

PMID- 24930689
TI  - Fe(II) uptake on natural montmorillonites. I. Macroscopic and spectroscopic
      characterization.
AB  - Iron is an important redox-active element that is ubiquitous in both engineered
      and natural environments. In this study, the retention mechanism of Fe(II) on
      clay minerals was investigated using macroscopic sorption experiments combined
      with Mossbauer and extended X-ray absorption fine structure (EXAFS) spectroscopy.
      Sorption edges and isotherms were measured under anoxic conditions on natural Fe
      bearing montmorillonites (STx, SWy, and SWa) having different structural Fe
      contents ranging from 0.5 to 15.4 wt % and different initial Fe redox states.
      Batch experiments indicated that, in the case of low Fe-bearing (STx) and
      dithionite-reduced clays, the Fe(II) uptake follows the sorption behavior of
      other divalent transition metals, whereas Fe(II) sorption increased by up to 2
      orders of magnitude on the unreduced, Fe(III)-rich montmorillonites (SWy and
      SWa). Mossbauer spectroscopy analysis revealed that nearly all the sorbed Fe(II)
      was oxidized to surface-bound Fe(III) and secondary Fe(III) precipitates were
      formed on the Fe(III)-rich montmorillonite, while sorbed Fe is predominantly
      present as Fe(II) on Fe-low and dithionite-reduced clays. The results provide
      compelling evidence that Fe(II) uptake characteristics on clay minerals are
      strongly correlated to the redox properties of the structural Fe(III). The
      improved understanding of the interfacial redox interactions between sorbed
      Fe(II) and clay minerals gained in this study is essential for future studies
      developing Fe(II) sorption models on natural montmorillonites. 

PMID- 24930690
TI  - Possible allergic contact dermatitis with reticulate postinflammatory
      pigmentation caused by hydroquinone.

PMID- 24930691
TI  - Variation of heart transplant rates in the United States during holidays.
AB  - BACKGROUND: Some cardiac transplant programs may upgrade listed patients to
      United Network for Organ Sharing (UNOS) 1A-status during the holidays. Whether
      more transplants actually occur during holidays is unknown. METHODS: We assessed
      rates of single-organ heart transplantation from 2001 to 2010 for recipients age
      >=18 yr using the UNOS database. Patients were stratified by transplantation
      during holiday (+/-3 d, n = 2375) and non-holiday periods (n = 16 112). Holidays
      included Easter/Spring break, Memorial Day, July 4th, Labor Day, Thanksgiving,
      and Christmas/New Years (winter holidays). Secondary analysis assessing
      transplant rates across seasons was also completed. RESULTS: Donor and recipient
      characteristics were similar between groups. Compared with non-holidays, July 4th
      had higher transplant rates (5.69 vs. 5.09 transplants/d, p = 0.03) while the
      winter holiday had lower transplant rates (4.50 vs. 5.09 transplants/d, p <
      0.01). There was a trend toward lower transplant rates for all holidays compared
      with non-holidays (p = 0.06). Transplant rates were significantly different
      across seasons with greater rates in spring and summer (p < 0.01). CONCLUSION:
      Heart transplant rates were higher during the July 4th and lower during the
      winter holidays. Although there was a higher likelihood of transplantation during
      the spring and summer seasons, upgrading patients to 1A status during most
      holidays may not improve their chances for transplantation.

PMID- 24930692
TI  - Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral
      radiorecurrent prostate cancer: a prospective two-centre study.
AB  - OBJECTIVE: To report the oncological and functional outcomes of hemi salvage high
      intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent
      prostate cancer. PATIENTS AND METHODS: Between 2009 and 2012, 48 patients were
      prospectively enrolled in two European centres. Inclusion criteria were
      biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic
      resonance imaging and >=1 positive biopsy in only one lobe. BCR was defined using
      Phoenix criteria (a rise by >=2 ng/mL above the nadir prostate specific antigen
      [PSA] level). The following schemes and criteria for functional outcomes were
      used: Ingelman-Sundberg score using International Continence Society (ICS)
      questionnaire (A and B), International prostate symptom score (IPSS),
      International Index of Erectile Function-5 (IIEF-5) points, the European
      Organisation for the Research and Treatment of Cancer (EORTC) quality of life
      questionnaires (QLQ C-30). HSH was performed under spinal or general anaesthesia
      using the Ablatherm(r) Integrated Imaging device. Patients with obstructive
      voiding symptoms at the time of treatment underwent an endoscopic bladder neck
      resection or incision during the same anaesthesia to prevent the risk of
      postoperative obstruction. RESULTS: After HSH the mean (sd) PSA nadir was 0.69
      (0.83) ng/mL at a median (interquartile range) follow-up of 16.3 (10.5-24.5)
      months. Disease progression occurred in 16/48 (33%). Of these, four had local
      recurrence in the untreated lobe and four bilaterally, six developed metastases,
      and two had rising PSA levels without local recurrence or radiological confirmed
      metastasis. Progression-free survival rates at 12, 18, and 24 months were 83%,
      64%, and 52%. Severe incontinence occurred in four of the 48 patients (8%), eight
      (17%) required one pad a day, and 36/48 (75%) were pad-free. The ICS
      questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for
      scores A and 0.6 (1.4) to 1.6 (3.0) for B. The mean (sd) IPSS and erectile
      function (IIEF-5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1)
      and from 11.2 (8.6) to 7.0 (5.8), respectively. The mean (sd) EORTC QLC-30 scores
      before and after HSH were 35.7 (8.6) vs 36.8 (8.6). CONCLUSION: HSH is a feasible
      therapeutic option in patients with unilateral radiorecurrent prostate cancer,
      which offers limited urinary and rectal morbidity, and preserves health-related
      quality of life.

PMID- 24930694
TI  - Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide
      nanoparticles in human oral and gastrointestinal cell systems.
AB  - Engineered nanoparticles (ENPs) are increasingly detected in water supply due to
      environmental release of ENPs as the by-products contained within the effluent of
      domestic and industrial run-off. The partial recycling of water laden with ENPs,
      albeit at ultra-low concentrations, may pose an uncharacterized threat to human
      health. In this study, we investigated the toxicity of three prevalent ENPs: zinc
      oxide, silver, and titanium dioxide over a wide range of concentrations that
      encompasses drinking water-relevant concentrations, to cellular systems
      representing oral and gastrointestinal tissues. Based on published in silico
      predicted water-relevant ENPs concentration range from 100 pg/L to 100 ug/L, we
      detected no cytotoxicity to all the cellular systems. Significant cytotoxicity
      due to the NPs set in around 100 mg/L with decreasing extent of toxicity from
      zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic
      zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress.
      The threshold concentrations of NPs that induced cytotoxic effect are at least
      two to five orders of magnitude higher than the permissible concentrations of the
      respective metals and metal oxides in drinking water. Based on these findings,
      the current estimated levels of NPs in potable water pose little cytotoxic threat
      to the human oral and gastrointestinal systems within our experimental
      boundaries.

PMID- 24930693
TI  - Patterns and predictors of antidepressant use in ambulatory cancer patients with
      common solid tumors.
AB  - PURPOSE: Depressive symptoms and antidepressant use are prevalent among cancer
      patients. We sought to identify determinants of prescribing commonly used
      antidepressants. PATIENTS AND METHODS: This multi-institutional study enrolled
      3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or
      lung. Five case-finding methods were used to identify patients with depressive
      symptoms. Logistic models were used to examine factors that impact antidepressant
      use. RESULTS: Approximately, 47% of patients were defined as having depressive
      symptoms. Clinicians rated being sad/depressed as one of the top three priority
      problems for 10.5% of patients. Antidepressants were prescribed in 19% of all
      patients, 25% with depressive symptoms and 14% nondepressed patients. After
      adjusting for other covariates, these variable categories were significantly
      associated with greater use of antidepressants: depressive symptoms, family
      history of depression, concurrent medication use, cancer treatment status, and
      certain other clinical and demographic variables. The strongest individual
      predictors were concurrent use of more than 10 medications (odds ratio [OR] =
      3.3), a family history of depression (OR = 2.2), sedative use (OR = 2.1), non
      Hispanic white race (OR = 2.0), and anxiolytics use (OR = 2.0). CONCLUSIONS:
      Depressive symptoms are found in nearly half of outpatients with cancer, and one
      fourth of patients with depressive symptoms are taking an antidepressant.
      Patients receiving antidepressants are more often those taking multiple
      medications, those with a depression diathesis, and those with more extensive
      cancer treatment. Patients who were younger, white, and female were also more
      likely to be taking antidepressants.

PMID- 24930695
TI  - Retinal pigment epithelium cells alter the pro-inflammatory response of retinal
      microglia to TLR-3 stimulation.
AB  - PURPOSE: Microglia are the local cells of the innate immunity in the retina. Toll
      like receptor (TLR) 3 is a receptor of the innate immune system, recognizing
      viral double-stranded RNA. Retinal pigment epithelium (RPE) cells express TLR-3
      and react to TLR-3 stimulation. In this study, we investigated the effect of TLR
      3-activated RPE on microglia. METHODS: Primary porcine RPE cells were prepared
      from freshly prepared pigs' eyes. Retinal microglia were prepared from porcine
      retina. Expression of the microglia marker Iba1 was evaluated using
      immunocytochemistry. RPE cells were treated with polyinosinic/polycytidylic acid
      (Poly I:C; 100 ng/ml, 1 MUg/ml, 10 MUg/ml, 100 MUg/ml) for 24 hr. Either the
      supernatant was applied to microglia for 6 or 24 hr or microglia cells were
      directly treated with Poly I:C for 6 and 24 hr. Expression of interleukin (IL)
      1beta, IL-6, tumour necrosis factor (TNF)alpha, IL-10, Cox2 and iNOS was
      evaluated in quantitative PCR. Phagocytosis was evaluated with a microscope-based
      and a fluoroscan-based phagocytosis assay. RESULTS: Retinal pigment epithelium
      (RPE) cells induce the expression of IL-6, IL-1beta and IL-10 in microglia cells.
      Microglia cells respond to Poly I:C stimulation in a concentration-dependent
      manner with the induction of IL-1beta, IL-6, TNFalpha, Cox2, iNOS and, to a
      lesser degree, IL-10. Stimulation of microglia cells with supernatant of Poly I:C
      treated RPE cells further elevated IL-6, IL-1beta and Cox2 expression, while it
      reduced the expression of iNOS. No changes in phagocytosis could be detected.
      CONCLUSIONS: TLR-3-activated RPE exacerbates inflammatory response of microglia
      in a differentiated manner. This indicates that viral infections in the RPE may
      have a proinflammatory influence on retinal microglia.

PMID- 24930697
TI  - Effect of a test meal on meal responses of satiation hormones and their
      association to insulin resistance in obese adolescents.
AB  - OBJECTIVE: The role of gastrointestinal (GI) hormones in the pathophysiology of
      obesity is unclear, although they are involved in the regulation of satiation and
      glucose metabolism. To (i) examine glucagon-like peptide 1 (GLP-1), amylin,
      ghrelin, and glucagon responses to a meal in obese adolescents and to (ii) test
      which GI peptides are associated with insulin resistance are presented. METHODS:
      A total of 16 obese (body mass index (BMI) >= 97th percentile for age and gender)
      and 14 control (BMI between 25th and 75th percentiles) adolescents were included.
      Subjects were instructed to eat a test meal (490 kcal). Plasma samples were
      collected for hormone and glucose analysis. RESULTS: Obese adolescents were
      insulin resistant as expressed by the Homeostasis Model Assessment (HOMA) index
      and had significantly increased fasting glucagon and amylin levels compared to
      the control group (P = 0.003 and 0.044, respectively). In response to the meal,
      the increase in GLP-1 levels was reduced in obese adolescents (P < 0.001). In
      contrast, amylin secretion was significantly increased in the obese population
      compared to the control group (P < 0.005). CONCLUSIONS: Obese adolescents have
      increased fasting glucagon and amylin levels and attenuated post-prandial GLP-1
      concentrations compared with the control group. These factors could contribute to
      the metabolic syndrome.

PMID- 24930698
TI  - Interconnected network of MnO2 nanowires with a "cocoonlike" morphology: redox
      couple-mediated performance enhancement in symmetric aqueous supercapacitor.
AB  - Low electronic conductivity and slow faradic processes limit the performance of
      MnO2 as an electrochemical pseudocapacitor with respect to cycling and power
      density. Herein, we report preparation of single-phase alpha-MnO2, composed of an
      interconnected nanowire network with "cocoonlike" morphology, and its application
      as electrode in a symmetric aqueous supercapacitor. Increased "effective" surface
      area, coexistence of micropores and mesopores, and enhanced electron transport in
      these nanowire networks result in a specific pseudocapacitance (CS) of 775 F.g(
      1) in 3 M KOH, derived from cyclic voltammetry in the potential window of -1 to
      +1 V at a scan rate of 2 mV.s(-1), the highest reported for two-electrode
      symmetric configuration. Furthermore, introduction of K4Fe(CN)6 as a redox-active
      additive to KOH results in ~7 times increase in energy density at a power density
      of ~6000 W.kg(-1). The presence of the Fe(CN)6(4-)/Fe(CN)6(3-) redox couple
      provides an electron buffer source compensating for the slow faradic reactions.
      The results demonstrate that this simple approach might be an effective way to
      enhance the redox kinetics and reversibility of transition metal oxide-based
      pseudocapacitors. 

PMID- 24930696
TI  - Using an instrumental variable to test for unmeasured confounding.
AB  - An important concern in an observational study is whether or not there is
      unmeasured confounding, that is, unmeasured ways in which the treatment and
      control groups differ before treatment, which affect the outcome. We develop a
      test of whether there is unmeasured confounding when an instrumental variable
      (IV) is available. An IV is a variable that is independent of the unmeasured
      confounding and encourages a subject to take one treatment level versus another,
      while having no effect on the outcome beyond its encouragement of a certain
      treatment level. We show what types of unmeasured confounding can be tested for
      with an IV and develop a test for this type of unmeasured confounding that has
      correct type I error rate. We show that the widely used Durbin-Wu-Hausman test
      can have inflated type I error rates when there is treatment effect
      heterogeneity. Additionally, we show that our test provides more insight into the
      nature of the unmeasured confounding than the Durbin-Wu-Hausman test. We apply
      our test to an observational study of the effect of a premature infant being
      delivered in a high-level neonatal intensive care unit (one with mechanical
      assisted ventilation and high volume) versus a lower level unit, using the excess
      travel time a mother lives from the nearest high-level unit to the nearest lower
      level unit as an IV.

PMID- 24930699
TI  - Expression of genes associated with cholesterol and lipid metabolism identified
      as a novel pathway in the early pathogenesis of Mycobacterium avium subspecies
      paratuberculosis-infection in cattle.
AB  - Johne's disease (JD) is a chronic disease affecting ruminants and other species
      caused by the pathogenic mycobacterium, Mycobacterium avium subsp.
      paratuberculosis (MAP). MAP has developed a multitude of mechanisms to persist
      within the host, and these in turn are counteracted by the host through various
      immune pathways. Identifying and characterising the different strategies employed
      by MAP to alter the host immune system in its favour, and thereby persist
      intracellularly, could hold the key to developing strategies to fight this
      disease. In this study we analysed a subset of bovine microarray data derived
      from early time points after experimental infection with MAP. A specifically
      developed integrated approach was used to identify and validate host genes
      involved in cholesterol homeostasis (24DHCR, LDLR, SCD-1), calcium homeostasis
      and anti-bacterial defence mechanisms, (CD38, GIMAP6) which were downregulated in
      response to MAP exposure. A trend for upregulation of granulysin gene expression
      in MAP-exposed cattle in comparison to unexposed cattle was also observed. From
      these analyses, a model of potential pathogen-host interactions involving these
      novel pathways was developed which indicates an important role for host lipids in
      mycobacterial survival and persistence.

PMID- 24930700
TI  - Linx mediates interaxonal interactions and formation of the internal capsule.
AB  - During the development of forebrain connectivity, ascending thalamocortical and
      descending corticofugal axons first intermingle at the pallial-subpallial
      boundary to form the internal capsule (IC). However, the identity of molecular
      cues that guide these axons remains largely unknown. Here, we show that the
      transmembrane protein Linx is robustly expressed in the prethalamus and lateral
      ganglionic eminence-derived corridor and on corticofugal axons, but not on
      thalamocortical axons, and that mice with a null mutation of Linx exhibit a
      complete absence of the IC. Moreover, regional inactivation of Linx either in the
      prethalamus and LGE or in the neocortex leads to a failure of IC formation.
      Furthermore, Linx binds to thalamocortical projections, and it promotes outgrowth
      of thalamic axons. Thus, Linx guides the extension of thalamocortical axons in
      the ventral forebrain, and subsequently, it mediates reciprocal interactions
      between thalamocortical and corticofugal axons to form the IC. 

PMID- 24930701
TI  - Increases in functional connectivity between prefrontal cortex and striatum
      during category learning.
AB  - Functional connectivity between the prefrontal cortex (PFC) and striatum (STR) is
      thought critical for cognition and has been linked to conditions like autism and
      schizophrenia. We recorded from multiple electrodes in PFC and STR while monkeys
      acquired new categories. Category learning was accompanied by an increase in beta
      band synchronization of LFPs between, but not within, the PFC and STR. After
      learning, different pairs of PFC-STR electrodes showed stronger synchrony for one
      or the other category, suggesting category-specific functional circuits. This
      category-specific synchrony was also seen between PFC spikes and STR LFPs, but
      not the reverse, reflecting the direct monosynaptic connections from the PFC to
      STR. However, causal connectivity analyses suggested that the polysynaptic
      connections from STR to the PFC exerted a stronger overall influence. This
      supports models positing that the basal ganglia "train" the PFC. Category
      learning may depend on the formation of functional circuits between the PFC and
      STR. 

PMID- 24930703
TI  - Long bone development requires a threshold of Hox function.
AB  - The Hoxd(Del(11-13)) mutant is one of the animal models for human synpolydactyly,
      characterized by short and syndactylous digits. Here we have characterized in
      detail the cartilage and bone defects in these mutants. We report two distinct
      phenotypes: (i) a delay and change in pattern of chondrocyte maturation of
      metacarpals/metatarsals and (ii) formation of a poor and not centrally positioned
      primary ossification center in the proximal-intermediate phalanx. In the
      metacarpals of Hoxd(Del(11-13)) mutants, ossification occurs postnataly, in the
      absence of significant Ihh expression and without the establishment of growth
      plates, following patterns similar to those of short bones. The strong
      downregulation in Ihh expression is associated with a corresponding increase of
      the repressor form of Gli3. To evaluate the contribution of this alteration to
      the phenotype, we generated double Hoxd(Del(11-13));Gli3 homozygous mutants.
      Intriguingly, these double mutants showed a complete rescue of the phenotype in
      metatarsals but only partial phenotypic rescue in metacarpals. Our results
      support Hox genes being required in a dose-dependent manner for long bone
      cartilage maturation and suggest that and excess of Gli3R mediates a significant
      part of the Hoxd(Del(11-13)) chondrogenic phenotype. 

PMID- 24930705
TI  - Quantifying GlosairTM 400 efficacy for surface disinfection of American Type
      Culture Collection strains and micro-organisms recently isolated from intensive
      care unit patients.
AB  - Microbial contamination of hospital surfaces may be a source of infection for
      hospitalized patients. We evaluated the efficacy of GlosairTM 400 against two
      American Type Culture Collection strains and 18 clinical isolates, placed on
      glass germ-carriers. Carriers were left to air-dry for 60 min and then exposed to
      a cycle before detection of any surviving micro-organisms. Antibiotic-susceptible
      Gram-negative bacilli were less susceptible (although not significantly) to this
      technique than resistant Gram-negative bacilli or Gram-positive cocci and yeasts
      (3, 3.4 and 4.6 log10 reduction, respectively). In conclusion, in areas that had
      not been cleaned, aerosolized hydrogen peroxide obtained >3 log10 mean
      destruction of patients' micro-organisms.

PMID- 24930702
TI  - Germ cells of the centipede Strigamia maritima are specified early in embryonic
      development.
AB  - We provide the first systematic description of germ cell development with
      molecular markers in a myriapod, the centipede Strigamia maritima. By examining
      the expression of Strigamia vasa and nanos orthologues, we find that the
      primordial germ cells are specified from at least the blastoderm stage. This is a
      much earlier embryonic stage than previously described for centipedes, or any
      other member of the Myriapoda. Using these genes as markers, and taking advantage
      of the developmental synchrony of Strigamia embryos within single clutches, we
      are able to track the development of the germ cells throughout embryogenesis. We
      find that the germ cells accumulate at the blastopore; that the cells do not
      internalize through the hindgut, but rather through the closing blastopore; and
      that the cells undergo a long-range migration to the embryonic gonad. This is the
      first evidence for primordial germ cells displaying these behaviours in any
      myriapod. The myriapods are a phylogenetically important group in the arthropod
      radiation for which relatively little developmental data is currently available.
      Our study provides valuable comparative data that complements the growing number
      of studies in insects, crustaceans and chelicerates, and is important for the
      correct reconstruction of ancestral states and a fuller understanding of how germ
      cell development has evolved in different arthropod lineages. 

PMID- 24930704
TI  - Dynamics of F-actin prefigure the structure of butterfly wing scales.
AB  - The wings of butterflies and moths consist of dorsal and ventral epidermal
      surfaces that give rise to overlapping layers of scales and hairs (Lepidoptera,
      "scale wing"). Wing scales (average length ~200 um) are homologous to insect
      bristles (macrochaetes), and their colors create the patterns that characterize
      lepidopteran wings. The topology and surface sculpture of wing scales vary
      widely, and this architectural complexity arises from variations in the
      developmental program of the individual scale cells of the wing epithelium. One
      of the more striking features of lepidopteran wing scales are the longitudinal
      ridges that run the length of the mature (dead) cell, gathering the cuticularized
      scale cell surface into pleats on the sides of each scale. While also present
      around the periphery of other insect bristles and hairs, longitudinal ridges in
      lepidopteran wing scales gain new significance for their creation of iridescent
      color through microribs and lamellae. Here we show the dynamics of the highly
      organized F-actin filaments during scale cell development, and present
      experimental manipulations of actin polymerization that reveal the essential role
      of this cytoskeletal component in wing scale elongation and the positioning of
      longitudinal ribs.

PMID- 24930706
TI  - The expression of the 14D9 catalytic antibody in suspended cells of Nicotiana
      tabacum cultures increased by the addition of protein stabilizers and by
      transference from Erlenmeyer flasks to a 2-L bioreactor.
AB  - The effect of two protein stabilizers (polyvinylpyrrolidone [PVP] and gelatine)
      on growth and 14D9 yield of Nicotiana tabacum cell suspension cultures (Ab-KDEL
      and sec-Ab) was analyzed. The addition of PVP at a concentration of 1.0 g L(-1)
      produced the highest total 14D9 yield (biomass + culture medium) in the Ab-KDEL
      line (4.82% total soluble protein [TSP]). With the addition of gelatine, the
      highest total 14D9 yield (2.48% TSP) was attained in the Ab-KDEL line at 5.0 g L(
      1) gelatine. When the Ab-KDEL suspended cells were cultured in a 2-L bioreactor,
      the highest 14D9 yield was 8.1% TSP at a 5% w/v inoculum size, which was the best
      14D9 yield so far obtained in the platforms tested (E. coli, N. tabacum leaves
      and seeds, N. tabacum hairy roots, and cell suspension cultures).

PMID- 24930707
TI  - Antigen-specific H1N1 influenza antibody responses in acute respiratory tract
      infections and their relation to influenza infection and disease course.
AB  - BACKGROUND: Early antibody responses to influenza infection are important in both
      clearance of virus and fighting the disease. Acute influenza antibody titers
      directed toward H1-antigens and their relation to infection type and patient
      outcomes have not been well investigated. OBJECTIVE: Using hemagglutination
      inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers
      in patients with influenza infection or another respiratory infection before and
      after the H1N1-pandemic influenza outbreak. Among patients with acute influenza
      infection we related duration of illness, severity of symptoms, and need for
      hospitalization to antibody titers. METHODS: There were 134 adult patients
      (average age 34.7) who presented to an urban academic emergency department (ED)
      from October through March during the 2008-2011 influenza seasons with symptoms
      of fever and a cough. Nasal aspirates were tested by viral culture, and
      peripheral blood serum was run in seven H1-subtype HI assays. RESULTS: Acutely
      infected influenza patients had markedly lower antibody titers for six of the
      seven pseudotype viruses. For the average over the seven titers (log units, base
      2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92)
      among patients who had a non-influenza respiratory illness, p<0.0001. Among
      patients with seasonal influenza infection, titers of some antibodies correlated
      with severity of symptoms and with total duration of illness (p<0.02).
      CONCLUSION: In patients with acute respiratory infections, lower concentrations
      of H1-influenza-specific antibodies were associated with influenza infection.
      Among influenza-infected patients, higher antibody titers were present in
      patients with a longer duration of illness and with higher severity-of-symptom
      scores.

PMID- 24930708
TI  - Quantification of hepatitis B surface antigen with the novel DiaSorin LIAISON XL
      Murex HBsAg Quant: correlation with the ARCHITECT quantitative assays.
AB  - BACKGROUND: Recent technologic innovations allow for quantitative assessment of
      hepatitis B surface antigen (HBsAg) levels in serum; this has been used to
      monitor the course of chronic HBV hepatitis (CHB) and predict treatment response.
      LIAISON-XL Murex HBsAg Quant assay (DiaSorin, Saluggia, I) is the newest
      immunoassay CE approved to quantify HBsAg. OBJECTIVES: To compare LIAISON-XL
      performances with ARCHITECT-QT HBsAg (Abbott Diagnostics, IL, USA), as reference
      test. STUDY DESIGN: Sequential serum samples (n=152) from 14 HBe-negative
      patients with CHB, the majority of them infected by HBV genotype D undergoing
      antiviral treatment, were retrospectively tested with both assays. The 2nd WHO
      Standard 00/588 for HBsAg was used as reference. RESULTS: LIAISON-XL and
      ARCHITECT-QT correlated by r=0.95, p<0.0001; by Bland-Altman analysis agreement
      of mean difference was 0.21 +/- 0.15 log 10 IU/mL, 95% CI: -0.07 to 0.5).
      Performance of LIAISON-XL against the 2nd WHO Standard was r=0.998, p<0.0001 (95%
      CI: 0.993-0.999) with results nearer to the expected WHO values compared to
      ARCHITECT-QT. Median baseline HBsAg level was similar with the two methods before
      antiviral treatment, throughout fluctuations of HBsAg level in treatment non
      responders and during the decrease of HBsAg titer in treatment responders.
      Correlation between HBsAg levels and HBV DNA was statistically significant for
      both the two immunoassays (LIAISON-XL: r=0.4988, 95% CI: 0.3452-0.6264, p<0.0001;
      ARCHITECT-QT: r=0.480, 95% CI: 0.3233-0.6111, p<0.0001). CONCLUSIONS: Correlation
      between HBsAg measurement with LIAISON-XL and ARCHITECT-QT was high. LIAISON-XL
      accurately quantified HBsAg in clinical samples at baseline or during antiviral
      therapy; it can be applied for HBsAg quantification in clinical practice and
      decision making in CHB.

PMID- 24930709
TI  - High-throughput DNA separation in nanofilter arrays.
AB  - We numerically investigated the dynamics of short double-stranded DNA molecules
      moving through a deep-shallow alternating nanofilter, by utilizing Brownian
      dynamics simulation. We propose a novel mechanism for high-throughput DNA
      separation with a high electric field, which was originally predicted by Laachi
      et al. [Phys. Rev. Lett. 2007, 98, 098106]. In this work, we show that DNA
      molecules deterministically move along different electrophoretic streamlines
      according to their length, owing to geometric constraint at the exit of the
      shallow region. Consequently, it is more probable that long DNA molecules pass
      over a deep well region without significant lateral migration toward the bottom
      of the deep well, which is in contrast to the long dwelling time for short DNA
      molecules. We investigated the dynamics of DNA passage through a nanofilter
      facilitating electrophoretic field kinematics. The statistical distribution of
      the DNA molecules according to their size clearly corroborates our assumption. On
      the other hand, it was also found that the tapering angle between the shallow and
      deep regions significantly affects the DNA separation performance. The current
      results show that the nonuniform field effect combined with geometric constraint
      plays a key role in nanofilter-based DNA separation. We expect that our results
      will be helpful in designing and operating nanofluidics-based DNA separation
      devices and in understanding the polymer dynamics in confined geometries. 

PMID- 24930710
TI  - Effect of pre-harvest methyl jasmonate treatments on ethylene production, water
      soluble phenolic compounds and fruit quality of Japanese plums.
AB  - BACKGROUND: The effects of pre-harvest methyl jasmonate (MJ) treatments on
      ethylene production, respiration rate, bioactive compounds and physico-chemical
      parameters of plum fruits (Prunus salicina Lindell cv. 'Fortune' and 'Friar')
      were investigated. Whole trees were sprayed once with an aqueous solution
      containing MJ (0, 1120 and 2240 mg L(-1)) 2 weeks before the anticipated
      commercial harvest for each cultivar. RESULTS: In both plum cultivars, 1120 mg L(
      1) MJ significantly increased hue angle of fruits. The fruit mass and geometric
      mean diameter were lower in MJ treatments while flesh firmness was higher, except
      at initial harvest date. Soluble solids concentration increased and titratable
      acidity decreased with MJ treatments. MJ-treated fruits exhibited higher levels
      of ethylene production and respiration rate. MJ was more effective in increasing
      water-soluble antioxidant activity, water-soluble phenolics and individual
      phenolics. Chlorogenic acid, caffeic acid, rutin, ferulic acid, naringenin and
      kaempferol contents significantly increased with 2240 mg L(-1) MJ. CONCLUSIONS:
      This study revealed that pre-harvest MJ treatments were effective in delaying
      softening of late-harvested fruits and increasing bioactive compounds of plum
      fruits.

PMID- 24930711
TI  - beta-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes
      relevant to anxiety and depression in mice.
AB  - Recent evidence suggests that the cannabinoid receptor subtype 2 (CB2) is
      implicated in anxiety and depression disorders, although few systematic studies
      in laboratory animals have been reported. The aim of the current experiments was
      to test the effects of the CB2 receptor potent-selective agonist beta
      caryophyllene (BCP) in animals subjected to models of anxiolytic- and
      antidepressant-like effects. Therefore effects of BCP (50mg/kg) on anxiety were
      assessed using the elevated plus maze (EPM), open field (OF), and marble burying
      test (MBT). However for depression, the novelty-suppressed feeding (NSF), tail
      suspension test (TST), and forced swim tests (FST) were used. Results indicated
      that adult mice receiving BCP showed amelioration of all the parameters observed
      in the EPM test. Also, BCP significantly increased the time spent in the center
      of the arena without altering the general motor activity in the OF test. This
      dose was also able to decrease the number of buried marbles and time spent
      digging in the MBT, suggesting an anti-compulsive-like effect. In addition, the
      systemic administration of BCP reduced immobility time in the TST and the FST.
      Finally, BCP treatment decreased feeding latency in the NSF test. Most
      importantly, pre-administration of the CB2 receptor antagonist AM630, fully
      abrogated the anxiolytic and the anti-depressant effects of BCP. Taken together,
      these preclinical results suggest that CB2 receptors may provide alternative
      therapeutic targets for the treatment of anxiety and depression. The possibility
      that BCP may ameliorate the symptoms of these mood disorders offers exciting
      prospects for future studies. 

PMID- 24930712
TI  - A resilience framework for promoting stable remission from depression.
AB  - A significant proportion of people in remission from depression will experience a
      recurrence of depression. One theoretical mechanism for this recurrence is that
      with each additional episode of depression, people become more sensitive to the
      deleterious effects of less powerful stressors. We propose that research on
      resilience - the ability to adapt to and recover from stress - can inform
      interventions to prevent recurrence in people in remission. We conceptualize
      resilience as a dynamic process that may be deficient in people in remission from
      depression, rather than as a static personal quality that is unattainable to
      people who have experienced psychopathology. The three aspects of resilience that
      we suggest are the most important to target to prevent recurrence are (1)
      improving stress recovery from minor daily stressors that may aid remitted people
      in coping with major stressors, (2) increasing positivity, like promoting
      positive emotions during stress, and (3) and training flexibility-the ability to
      identify different demands in the environment and employ the appropriate coping
      strategy to meet those demands. We offer suggestions for the appropriate
      assessment of changes in resilience in remitted people and provide some examples
      of effective resilience interventions. 

PMID- 24930713
TI  - Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes
      correlates with beta-catenin accumulation.
AB  - AIMS: beta-Catenin accumulation promotes proliferation. However, the correlation
      between proliferation of colorectal epithelium and beta-catenin in type 2
      diabetes mellitus (DM) patients remains unclear. METHODS: Colorectal epithelium
      samples from distal ends of colorectal adenocarcinomas without histological
      aberrances were divided into two groups: DM patients with type 2 DM for more than
      1year (n=27) and non-DM patients without hyperglycemia (n=20). Samples from
      patients without colorectal epithelial disease or hyperglycemia served as a
      control group (n=6). Proliferative index was calculated as the percentage of
      proliferating cell nuclear antigen positive cells. Wnt/beta-catenin signaling was
      assessed immunohistochemically and phosphorylation of beta-catenin was assessed
      by immunofluorescence. RESULTS: Compared with the non-DM or control group, the
      proliferative index and expression of lactate dehydrogenase A and Wnt/beta
      catenin signaling were significantly higher in the DM group (all p<0.01). The
      proliferative index correlated positively with beta-catenin expression (Spearman
      correlation coefficient=0.55; p<0.01). Reduced phosphorylation at serine 33/37
      and increased phosphorylation at serine 675 of beta-catenin were detected in the
      DM group (all p<0.01). CONCLUSIONS: Enhanced proliferation, accompanied by
      increased aerobic glycolysis, was detected in colorectal epithelium of patients
      with diabetes. beta-Catenin accumulation with altered phosphorylation correlated
      with the proliferative changes.

PMID- 24930714
TI  - Prevalence, incidence and progression of peripheral arterial disease in Asian
      Indian type 2 diabetic patients.
AB  - OBJECTIVE: To assess the prevalence, incidence, etiology and factors related to
      progression of peripheral arterial disease [PAD] in Asian Indian type 2 diabetic
      patients. METHODS: Patients with type 2 diabetes (T2DM), with multiple Doppler
      studies done between 2001 and 2011 at a tertiary diabetes center in south India,
      were included. Baseline clinical and biochemical characteristics and ankle
      brachial index [ABI] measurements were abstracted from the electronic medical
      records. RESULTS: 2512 T2DM patients were followed for an average of 7years. 7.6%
      of the study population had PAD in 2001 [women, 11.8%; men, 5.1%] with an
      adjusted odds ratio (OR) of 3.09 [confidence interval (CI): 1.9-4.9] for women.
      Prevalent PAD was associated with increased mortality [hazards ratio (HR) 3.3,
      CI: 1.4-7.7]. 280 new patients of PAD were identified - crude incidence, 17/1000
      patient years with higher rates in females [HR 1.94, CI: 1.4-2.7]. Age and
      duration of diabetes were the other predictors of incident PAD. Progression of
      PAD was seen in 16.5% of patients, with age (p=0.002) and HbA1c (p=0.022) being
      the predictors. CONCLUSIONS: Women had a higher prevalence of PAD. Older age,
      female gender and duration of diabetes were related to an increased incidence of
      PAD. An elevated HbA1c being associated with progression of PAD stresses the need
      for strict control of diabetes.

PMID- 24930715
TI  - Clinical evaluation of a novel microneedle device for intradermal delivery of an
      influenza vaccine: are all delivery methods the same?
AB  - The skin provides the largest immune barrier to infection and is a readily
      accessible site for vaccination, although intradermal (ID) injection can be
      challenging. The MicronJetTM microneedle is a novel device that consistently
      injects antigens very close to the skin's dendritic cells. A dose-sparing ID
      injection study was conducted in 280 healthy adult volunteers using trivalent
      virosomal adjuvanted influenza vaccine. ID injection of 3 MUg using the
      MicronJetTM was well tolerated and showed a statistically higher geometric mean
      fold rise than the same dose ID using a conventional needle (Mantoux technique)
      for the H1N1 and B strains or a 15 MUg intramuscular (IM) injection for the H3N2
      strain. Thus, the immune response appears to partially depend on the delivery
      device and route of injection. The MicronJetTM may allow dose-sparing, yet give a
      superior response in influenza vaccination and warrants further clinical
      evaluation.

PMID- 24930716
TI  - Cost-effectiveness of influenza vaccination in prior pneumonia patients in
      Israel.
AB  - Pneumonia is a common complication of influenza infection, and accounts for the
      majority of influenza mortality. Both the WHO and the Ministry of Health in
      Israel prioritize seasonal influenza vaccination primarily on the basis of age
      and specific co-morbidities. Here we consider whether the targeting of
      individuals previously infected with pneumonia for influenza vaccination would be
      a cost-effective addition to the current policy. We performed a retrospective
      cohort data analysis of 163,990 cases of pneumonia hospitalizations and 1,305,223
      cases of outpatient pneumonia from 2004 to 2012, capturing more than 54% of the
      Israeli population. Our findings demonstrate that patients infected with
      pneumonia in the year prior had a substantially higher risk of becoming infected
      with pneumonia in subsequent years (relative risk >2.34, p<0.01). Results
      indicated that the benefit of targeting for influenza vaccination patients
      hospitalized with pneumonia in prior year would be cost-saving regardless of age.
      Complementing the current policy with the targeting of prior pneumonia patients
      would require vaccination of only a further 2.3% of the Israeli population to
      save additional 204-407 quality-adjusted life years (QALYs) annually at a mean
      price of 58-1056 USD/QALY saved. Global uncertainty analysis demonstrates that
      the cost-effectiveness of adding this policy is robust over a vast range of
      conditions. As prior pneumonia patients are currently not prioritized for
      influenza vaccination in Israel, nor elsewhere, this study suggests a novel
      supplement of current policies to improve cost-effectiveness of influenza
      vaccination. Future studies should use case-control study to further evaluate the
      effectiveness of vaccination in prior pneumonia patients. 

PMID- 24930718
TI  - Gallbladder tumor and pseudotumor: Diagnosis and management.
AB  - The most common gallbladder disease, by far, is cholecystolithiasis.
      Nevertheless, the discovery of abnormal thickening of the gallbladder wall or a
      tumorous lesion (with or without gallstones), is a frequent problem. The
      physician who confronts this finding must be aware of the various lesions to be
      considered in the differential diagnosis, whether neoplastic or pseudotumoral,
      epithelial or not, benign or malignant. Because of the particularly grim
      prognosis of gallbladder cancer, especially when discovered at a late stage, it
      is especially important to focus on the potential for malignant degeneration of
      any gallbladder lesion. Imaging plays an important role in distinguishing these
      lesions; ultrasound remains the key diagnostic tool for gallbladder disease, but
      other modalities including CT and MRI may help to characterize these lesions. The
      resulting treatment strategies vary widely depending on the risk of malignancy. A
      wide and extensive resection is recommended for malignant lesions; prophylactic
      cholecystectomy is recommended for lesions at risk for malignant degeneration
      while observation is indicated for purely benign lesions. 

PMID- 24930719
TI  - Fitness prospects: effects of age, sex and recruitment age on reproductive value
      in a long-lived seabird.
AB  - Reproductive value is an integrated measure of survival and reproduction
      fundamental to understanding life-history evolution and population dynamics, but
      little is known about intraspecific variation in reproductive value and factors
      explaining such variation, if any. By applying generalized additive mixed models
      to longitudinal individual-based data of the common tern Sterna hirundo, we
      estimated age-specific annual survival probability, breeding probability and
      reproductive performance, based on which we calculated age-specific reproductive
      values. We investigated effects of sex and recruitment age (RA) on each trait. We
      found age effects on all traits, with survival and breeding probability declining
      with age, while reproductive performance first improved with age before levelling
      off. We only found a very small, marginally significant, sex effect on survival
      probability, but evidence for decreasing age-specific breeding probability and
      reproductive performance with RA. As a result, males had slightly lower age
      specific reproductive values than females, while birds of both sexes that
      recruited at the earliest ages of 2 and 3 years (i.e. 54% of the tern population)
      had somewhat higher fitness prospects than birds recruiting at later ages. While
      the RA effects on breeding probability and reproductive performance were
      statistically significant, these effects were not large enough to translate to
      significant effects on reproductive value. Age-specific reproductive values
      provided evidence for senescence, which came with fitness costs in a range of 17
      21% for the sex-RA groups. Our study suggests that intraspecific variation in
      reproductive value may exist, but that, in the common tern, the differences are
      small. 

PMID- 24930717
TI  - Evaluation of recombinant Mycoplasma hyopneumoniae P97/P102 paralogs formulated
      with selected adjuvants as vaccines against mycoplasmal pneumonia in pigs.
AB  - Pig responses to recombinant subunit vaccines containing fragments of eight
      multifunctional adhesins of the Mycoplasma hyopneumoniae (Mhp) P97/P102 paralog
      family formulated with Alhydrogel((r)) or MontanideTM Gel01 were compared with a
      commercial bacterin following experimental challenge. Pigs, vaccinated
      intramuscularly at 9, 12 and 15 weeks of age with either of the recombinant
      formulations (n=10 per group) or Suvaxyn((r)) M. hyo (n=12), were challenged with
      Mhp strain Hillcrest at 17 weeks of age. Unvaccinated, challenged pigs (n=12)
      served as a control group. Coughing was assessed daily. Antigen-specific antibody
      responses were monitored by ELISA in serum and tracheobronchial lavage fluid
      (TBLF), while TBLF was also assayed for cytokine responses (ELISA) and bacterial
      load (qPCR). At slaughter, gross and histopathology of lungs were quantified and
      damage to epithelial cilia in the porcine trachea was evaluated by scanning
      electron microscopy. Suvaxyn((r)) M. hyo administration induced significant
      serological responses against Mhp strain 232 whole cell lysates (wcl) and
      recombinant antigen F3P216, but not against the remaining vaccine subunit
      antigens. Alhydrogel((r)) and MontanideTM Gel01-adjuvanted antigen induced
      significant antigen-specific IgG responses, with the latter adjuvant eliciting
      comparable Mhp strain 232 wcl specific IgG responses to Suvaxyn((r)) M. hyo. No
      significant post-vaccination antigen-specific mucosal responses were detected
      with the recombinant vaccinates. Suvaxyn((r)) M. hyo was superior in reducing
      clinical signs, lung lesion severity and bacterial load but the recombinant
      formulations offered comparable protection against cilial damage. Lower IL-1beta,
      TNF-alpha and IL-6 responses after challenge were associated with reduced lung
      lesion severity in Suvaxyn((r)) M. hyo vaccinates, while elevated pathology
      scores in recombinant vaccinates corresponded to cytokine levels that were
      similarly elevated as in unvaccinated pigs. This study highlights the need for
      continued research into protective antigens and vaccination strategies that will
      prevent Mhp colonisation and establishment of infection. 

PMID- 24930720
TI  - Whole genome single-nucleotide variation profile-based phylogenetic tree building
      methods for analysis of viral, bacterial and human genomes.
AB  - Next-generation sequencing data can be mapped to a reference genome to identify
      single-nucleotide polymorphisms/variations (SNPs/SNVs; called SNPs hereafter). In
      theory, SNPs can be compared across several samples and the differences can be
      used to create phylogenetic trees depicting relatedness among the samples.
      However, in practice this is difficult because currently there is no stand-alone
      tool that takes SNP data directly as input and produces phylogenetic trees. In
      response to this need, PhyloSNP application was created with two analysis methods
      1) a quantitative method that creates the presence/absence matrix which can be
      directly used to generate phylogenetic trees or creates a tree from a shrunk
      genome alignment (includes additional bases surrounding the SNP position) and 2)
      a qualitative method that clusters samples based on the frequency of different
      bases found at a particular position. The algorithms were used to generate trees
      from Poliovirus, Burkholderia and human cancer genomics NGS datasets.
      AVAILABILITY: PhyloSNP is freely available for download at
      http://hive.biochemistry.gwu.edu/dna.cgi?cmd=phylosnp.

PMID- 24930721
TI  - D6 PROTEIN KINASE activates auxin transport-dependent growth and PIN-FORMED
      phosphorylation at the plasma membrane.
AB  - The directed cell-to-cell transport of the phytohormone auxin by efflux and
      influx transporters is essential for proper plant growth and development. Like
      auxin efflux facilitators of the PIN-FORMED (PIN) family, D6 PROTEIN KINASE
      (D6PK) from Arabidopsis thaliana localizes to the basal plasma membrane of many
      cells, and evidence exists that D6PK may directly phosphorylate PINs. We find
      that D6PK is a membrane-bound protein that is associated with either the basal
      domain of the plasma membrane or endomembranes. Inhibition of the trafficking
      regulator GNOM leads to a rapid internalization of D6PK to endomembranes.
      Interestingly, the dissociation of D6PK from the plasma membrane is also promoted
      by auxin. Surprisingly, we find that auxin transport-dependent tropic responses
      are critically and reversibly controlled by D6PK and D6PK-dependent PIN
      phosphorylation at the plasma membrane. We conclude that D6PK abundance at the
      plasma membrane and likely D6PK-dependent PIN phosphorylation are prerequisites
      for PIN-mediated auxin transport.

PMID- 24930722
TI  - Left-right organizer flow dynamics: how much cilia activity reliably yields
      laterality?
AB  - Internal organs are asymmetrically positioned inside the body. Embryonic motile
      cilia play an essential role in this process by generating a directional fluid
      flow inside the vertebrate left-right organizer. Detailed characterization of how
      fluid flow dynamics modulates laterality is lacking. We used zebrafish genetics
      to experimentally generate a range of flow dynamics. By following the development
      of each embryo, we show that fluid flow in the left-right organizer is asymmetric
      and provides a good predictor of organ laterality. This was tested in mosaic
      organizers composed of motile and immotile cilia generated by dnah7 knockdowns.
      In parallel, we used simulations of fluid dynamics to analyze our experimental
      data. These revealed that fluid flow generated by 30 or more cilia predicts 90%
      situs solitus, similar to experimental observations. We conclude that cilia
      number, dorsal anterior motile cilia clustering, and left flow are critical to
      situs solitus via robust asymmetric charon expression. 

PMID- 24930723
TI  - [Cognitive remediation and work outcome in schizophrenia].
AB  - Recovery is partly defined by the patients' capacity to work, since doing well in
      a job favors hope and responsibilities' taking. Diminished job placement or
      tenure is linked with cognitive disorders, which impact directly and indirectly
      (through negative symptoms) functional outcomes. Attention, executive functions
      and working memory disorders can result in an alteration of the ability to manage
      the tasks required in the workplace. Executive function, working memory and
      social cognition disorders may also have an impact on behavior in relationships.
      Cognitive disorders do not automatically directly contribute to vocational
      outcome, yet their effects may be mediated by other variables such as symptoms,
      metacognition, social skills and intrinsic motivation. Then, since all these
      dimensions have to be taken into account, reducing the impact of cognitive
      troubles becomes a major challenge for the care of schizophrenia. Cognitive
      remediation is the more effective therapeutic tool to reduce cognitive
      dysfunctions. It rests in particular on the development of new strategies that
      allow taking concrete situations into account more efficiently. Cognitive
      remediation reduces the detrimental consequences of cognitive disorders and
      permits their compensation. It has emerged as an effective treatment, that
      improves not only cognitive abilities but also functioning, as it has been shown
      by numerous randomized controlled studies and several meta-analyses. The present
      article considers the effects on cognitive remediation on work function in
      schizophrenia. Several randomized controlled trials that compared supported
      employment alone versus supported employment associated with cognitive
      remediation showed significant improvement of employment rates in the latter
      condition. These results favor the use of cognitive remediation before job
      placement. The specific needs of the occupation that will be provided and the
      cognitive profile of the user should be taken into account. 

PMID- 24930724
TI  - [Two "hybrid" vocational services for people with a severe mental illness in
      France and Quebec].
AB  - Many different types of vocational programs (services) exist to help people with
      severe mental disorders (e.g., schizophrenia) integrate the regular labor market:
      sheltered workshops, social enterprises, and supported employment programs to
      name a few. Each type of vocational services has its specificities: on one hand,
      some of them are following the "train and place" approach. For example, sheltered
      workshops offer to people with a severe mental illness a training during a long
      period of, with a small proportion obtaining competitive employment. On the other
      hand, other programs adopt the "place and train" philosophy, such as supported
      employment programs, in which employment specialists help people obtain a
      competitive job as fast as possible with no requested training. This article
      presents two original vocational services, the Messidor's sheltered workshops in
      France and the Acces-Cible SMT supported employment program in Quebec, following
      an "hybrid" approach including both philosophies "place and train" and "train and
      place". More particularly, they are both aiming at competitive employment on the
      regular labor market for people with a severe mental illness, with a different
      length of training. Messidor consists of a sheltered workplace for people with a
      severe mental illness in France, using this time of transition in the workshops
      as a tool to obtain a competitive job. Thanks to three key factors, Messidor
      succeeds in placing many of their workers in the French regular labor market: (1)
      Workers with severe mental disorders work on tasks and workplaces similar to
      those in regular labor market; (2) Messidor's managers have small teams (5-7
      persons) that offer a nearby and personalized management to workers; (3) Each
      worker is followed by a Messidor's employment counsellor, to build together a
      working plan and put in place work strategies to obtain a competitive job. This
      "double management" seems to be a key ingredient of this support as it promotes
      some success in getting a job as well as in developing some recovery effects.
      Acces-Cible SMT located in Montreal (Quebec, Canada) is also an interesting
      "hybrid" program since people with severe mental disorders can be supported by a
      counsellor, with a short period of training (a 28-week program with 6 steps)
      before integrating the regular labor market. The philosophy of Acces-Cible SMT is
      to consider their clients as normal persons more than as patients, and its
      objective is mainly to restore confidence and self-esteem of the person by
      putting emphasis on their professional skills. Meetings in groups, practicums in
      the workplace, and the utilization of job search strategies are essential
      ingredients of Acces-Cible SMT, which are also efficient tools to develop a
      better empowerment of the person. Indeed, the common ingredients/elements of
      these two vocational services, Messidor and Acces-Cible SMT, seem to be the
      development of empowerment for people with severe mental disorders. The
      scientific literature supports that empowerment is one of the key factors of
      recovery for people with a mental illness, a recovery process that can be
      illustrated by their work integration in the regular labor market as a final
      goal. 

PMID- 24930725
TI  - [Induction of labor in twin pregnancies compared to singleton pregnancies; risk
      factors for failure].
AB  - OBJECTIVES: The aim of this study was to evaluate the modalities of induction of
      labour in twin pregnancies compared with singleton pregnancies and to identify
      risk factors for failure. MATERIALS ET METHODS: A retrospective population-based
      study was conducted at the Toulouse University Hospital to compare a cohort of
      diamniotic twin gestations (Twin A in vertex presentation), with induction of
      labour >=36 weeks of gestation, between January 2007 and December 2012, to a
      singleton's cohort that were induced >=36 weeks of gestation during the 2007
      year. One singleton pregnancy was matched for each twin pregnancy with parity and
      gestational age. RESULTS: One hundred and fifty-six twins pregnancies met the
      inclusion criteria for an induction of labor and were compared to 156 single
      pregnancies. The same and standard protocol of induction of labor was used for
      the two cohorts (intrauterine balloon catheter+/-dinoprostone/ocytocine). The
      cesarean section rate for failed labor induction (cesarean in latent phase) was
      similar in the 2 populations (14.7% for twin vs 13.5% for single; P=0.66). The
      factors associated to failed induction of labor in the total population were
      nulliparity (OR=1.49) and Bishop score<6 at the beginning of the induction
      (OR=2.83). CONCLUSION: Twin did not appear as risk of failed induction. The
      protocol for induction of labor in singletons may be safely proposed to twin
      gestations.

PMID- 24930726
TI  - [Pregnancy and substance use in France: a literature review].
AB  - OBJECTIVES: Substance use during pregnancy is an important public health issue.
      It requires identifying at-risk populations and risk perception among women.
      MATERIALS AND METHODS: A literature review was conducted. It included French
      studies conducted since 2000 on substance use during pregnancy (tobacco, alcohol,
      marijuana, psychotropic drugs) and risk perception. RESULTS: In France, in 2010,
      24% of pregnant women smoke--17% in the 3rd trimester. Depending on studies, the
      prevalence of alcohol use ranged from 12 to 63% and binge drinking ranged from 1
      to 7%; daily drinking was below 0.5%. Marijuana use ranged from 1 to 3%, and
      psychotropic drugs ranged from 2 to 4%. Little research has been dedicated to
      risk perception. Studies show a lack of awareness about the equivalence of risks
      between fermented and distilled beverages and about the risks of moderate smoking
      during pregnancy. CONCLUSION: Data is lacking to characterize at-risk populations
      and mechanisms underlying risky behaviors.

PMID- 24930727
TI  - [HPV contamination of endocavity vaginal ultrasound probes].
AB  - While the use of endovaginal ultrasound probes is increasing, the risk of
      contamination of women with endocavity vaginal probes was not assessed. In
      particular, the clinical significance of detection of human papillomavirus (HPV)
      infection, the most common sexually transmitted viral infection, on endovaginal
      ultrasound probes is uncertain. The recommendations of good practice for
      decontamination of these probes developed by the High Council for Public Health
      and the Academy of Medicine have not been evaluated. The objective of this
      article was to review recent publications concluding to the detection of HPV and
      human cellular DNA after gynecological examination and disinfection of vaginal
      ultrasound probes. 

PMID- 24930729
TI  - Protein kinases as cardiovascular therapeutic targets.

PMID- 24930730
TI  - Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with
      ischemic stroke and treated with aspirin.
AB  - As the key point of function for aspirin to educe anti-platelet effects,
      cyclooxygenase-1 (COX-1) gene polymorphisms have long been suspected as a
      potential cause for aspirin nonresponsiveness. But this hypothesis has not been
      confirmed by large longitudinal studies. This study prospectively evaluated the
      impacts of COX-1 gene polymorphisms on stroke recurrence and other vascular
      events in a large cohort of Chinese patients with ischemic stroke and treated
      with aspirin. Between December 2009 and October 2012, consecutive patients with
      ischemic stroke and treated with aspirin were enrolled. Polymorphisms of four
      alleles (rs1330344, rs10306114, rs3842788 and rs5788) in COX-1 gene were
      determined at baseline. The primary endpoint was a composite of nonfatal ischemic
      stroke, myocardial infarction, and death from cardiovascular causes. Impacts of
      COX-1 gene polymorphisms on vascular outcomes were evaluated with multivariate
      analysis. A total of 859 patients were included in data analysis. The minor
      allele frequencies of rs1330344, rs10306114, rs3842788 and rs5788 were 38.53%,
      0.12%, 6.64% and 5.53%, respectively. During 14.64 +/- 7.44 months of follow-up,
      primary endpoint was observed in 67 (7.80%) patients. Incidence of primary
      endpoint was higher in patients with CC genotype of rs1330344 than in patients
      with CT or TT genotype (HR=1.916, 95% CI: 1.126-3.260, P=0.016). After being
      adjusted for potential confounding factors, rs1330344 CC genotype was still
      independently associated with incidence of primary endpoint (HR=1.958, 95% CI:
      1.151-3.332, P=0.013). The impacts of other three tested polymorphisms on primary
      endpoint were unremarkable. In conclusion, in Chinese patients with ischemic
      stroke and treated with aspirin, CC genotype of rs1330344 may increase the risk
      of subsequent vascular events.

PMID- 24930731
TI  - Promoter characterization and functional association with placenta of porcine
      MAGEL2.
AB  - MAGEL2 (melanoma antigen-like gene 2) is essential for circadian function,
      metabolism and reproduction in mammals. This study was conducted to investigate
      transcriptional regulation and functional importance in the placenta of porcine
      MAGEL2. Quantitative real-time PCR showed that MAGEL2 was highly expressed in
      porcine hypothalamus, pituitary and placenta (P<0.05). The gene was down
      regulated in Meishan but up-regulated in Duroc placentas from 25 days post-coitum
      (dpc) to 105 dpc (P<0.01). Dual luciferase assay demonstrated that the region 
      151/+110 had the highest promoter activity. Of the g. -712C>G and g. -708T>C
      polymorphisms in MAGEL2 promoter, -712C and -708T were observed to be predominant
      in Large White, Landrace and Duroc populations, while -712G and -708C were
      predominant in Meishan and Rongchang populations. Moreover, -712C>G and -708T>C
      had significant effects on MAGEL2 transcription (P<0.05) and placental efficiency
      (P<0.01). In conclusion, -151/+110 harbors the basal promoter of porcine MAGEL2.
      The region upstream the basal promoter contains repressive cis-elements. And,
      MAGEL2 is essential in porcine placenta.

PMID- 24930728
TI  - Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST
      segment elevation myocardial infarction: a randomised phase 2 trial.
AB  - BACKGROUND: p38 MAPK inhibition has potential myocardial protective effects. We
      assessed losmapimod, a potent oral p38 MAPK inhibitor, in patients with non-ST
      segment elevation myocardial infarction (NSTEMI) in a double-blind, randomised,
      placebo-controlled trial. METHODS: From October, 2009, to November, 2011, NSTEMI
      patients were assigned oral losmapimod (7.5 mg or 15.0 mg loading dose followed
      by 7.5 mg twice daily) or matching placebo in a 3:3:2 ratio. Safety outcomes were
      serious adverse events and alanine aminotransferase (ALT) concentrations over 12
      weeks, and cardiac events (death, myocardial infarction, recurrent ischaemia,
      stroke, and heart failure) at 90 days. Efficacy outcomes were high-sensitivity C
      reactive protein (hsCRP) and B-type natriuretic peptide (BNP) concentrations at
      72 h and 12 weeks, and troponin I area under the curve (AUC) over 72 h. The
      losmapimod groups were pooled for analysis. This trial is registered with
      ClinicalTrials.gov, number NCT00910962. FINDINGS: Of 535 patients enrolled, 526
      (98%) received at least one dose of study treatment (losmapimod n=388 and placebo
      n=138). Safety outcomes did not differ between groups. HsCRP concentrations at 72
      h were lower in the losmapimod group than in the placebo group (geometric mean
      64.1 nmol/L, 95% CI 53.0-77.6 vs 110.8 nmol/L, 83.1-147.7; p=0.0009) but were
      similar at 12 weeks. Early geometric mean BNP concentrations were similar at 72 h
      but significantly lower in the losmapimod group at 12 weeks (37.2 ng/L, 95% CI
      32.3-42.9 vs 49.4 ng/L, 38.7-63.0; p=0.04). Mean troponin I AUC values did not
      differ. INTERPRETATION: p38 MAPK inhibition with oral losmapimod was well
      tolerated in NSTEMI patients and might improve outcomes after acute coronary
      syndromes. FUNDING: GlaxoSmithKline.

PMID- 24930732
TI  - Disentangling plastic and genetic changes in body mass of Siberian jays.
AB  - Spatial and temporal phenotypic differentiation in mean body size is of
      commonplace occurrence, but the underlying causes remain often unclear: both
      genetic differentiation in response to selection (or drift) and environmentally
      induced plasticity can create similar phenotypic patterns. Studying changes in
      body mass in Siberian jays (Perisoreus infaustus) over three decades, we
      discovered that mean body mass declined drastically (ca. 10%) over the first two
      decades, but increased markedly thereafter back to almost the initial level.
      Quantitative genetic analyses revealed that although body mass was heritable
      (h(2) = 0.46), the pronounced temporal decrease in body mass was mainly a product
      of phenotypic plasticity. However, a concomitant and statistically significant
      decrease in predicted breeding values suggests a genetic component to this
      change. The subsequent increase in mean body mass was indicated to be entirely
      due to plasticity. Selection on body mass was estimated to be too weak to fully
      account for the observed genetic decline in body mass, but bias in selection
      differential estimates due to environmental covariance between body mass and
      fitness is possible. Hence, the observed body mass changes appear to be driven
      mainly by phenotypic plasticity. Although we were not able to identify the
      ecological driver of the observed plastic changes, the results highlight the
      utility of quantitative genetic approaches in disentangling genetic and
      phenotypic changes in natural populations.

PMID- 24930734
TI  - The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase
      complexes and controls osteogenic differentiation.
AB  - The ubiquitin-like SUMO system regulates gene expression, but the molecular
      insights into this process are incomplete. We show that the SUMO-specific
      isopeptidase SENP3 controls H3K4 methylation by regulating histone-modifying
      SET1/MLL complexes. SET1/MLL complexes are composed of a histone
      methyltransferase and the regulatory components WDR5, RbBP5, Ash2L, and DPY-30.
      MLL1/MLL2 complexes contain menin as additional component and are particularly
      important for the activation of HOX genes. We demonstrate that SENP3 is
      associated with MLL1/MLL2 complexes and catalyzes deSUMOylation of RbBP5. This is
      required for activation of a subset of HOX genes, including the developmental
      regulator DLX3. In the absence of SENP3, the association of menin and Ash2L with
      the DLX3 gene is impaired, leading to decreased H3K4 methylation and reduced
      recruitment of active RNA polymerase II. Importantly, the SENP3-DLX3 pathway
      dictates osteogenic differentiation of human stem cells, thus delineating the
      importance of balanced SUMOylation for epigenetic control of gene expression
      programs. 

PMID- 24930736
TI  - Efficacy of traditional and alternative sunitinib treatment schedules in Japanese
      patients with metastatic renal cell carcinoma.
AB  - We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off)
      and alternative sunitinib treatment schedules for Japanese patients with
      metastatic renal cell carcinoma. We retrospectively investigated 54 patients who
      received sunitinib for metastatic renal cell carcinoma between May 2006 and June
      2012: 32 received a traditional treatment schedule and 22 received an alternative
      schedule. According to the Memorial Sloan-Kettering Cancer Center risk
      classification, five patients had favorable prognoses, 42 had intermediate
      prognoses and seven had poor prognoses. The mean observation periods were 16.3
      and 20 months for the traditional and alternative schedule groups, respectively.
      Adverse events were significantly less common in the alternative schedule group,
      including most high-grade events. In the traditional and alternative schedule
      groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median
      progression-free survival times were 4.1 and 11.3  months (P = 0.031), and median
      overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each
      of these measures was better in the group of patients who received an alternative
      treatment schedule, suggesting that individualized changes to the sunitinib
      administration schedule can be effective.

PMID- 24930733
TI  - The calcineurin signaling network evolves via conserved kinase-phosphatase
      modules that transcend substrate identity.
AB  - To define a functional network for calcineurin, the conserved Ca(2+)/calmodulin
      regulated phosphatase, we systematically identified its substrates in S.
      cerevisiae using phosphoproteomics and bioinformatics, followed by copurification
      and dephosphorylation assays. This study establishes new calcineurin functions
      and reveals mechanisms that shape calcineurin network evolution. Analyses of
      closely related yeasts show that many proteins were recently recruited to the
      network by acquiring a calcineurin-recognition motif. Calcineurin substrates in
      yeast and mammals are distinct due to network rewiring but, surprisingly, are
      phosphorylated by similar kinases. We postulate that corecognition of conserved
      substrate features, including phosphorylation and docking motifs, preserves
      calcineurin-kinase opposition during evolution. One example we document is a
      composite docking site that confers substrate recognition by both calcineurin and
      MAPK. We propose that conserved kinase-phosphatase pairs define the architecture
      of signaling networks and allow other connections between kinases and
      phosphatases to develop that establish common regulatory motifs in signaling
      networks.

PMID- 24930735
TI  - Genetic diversity and population structure of long-tailed macaque (Macaca
      fascicularis) populations in Peninsular Malaysia.
AB  - BACKGROUND: The genetic diversity and structure of long-tailed macaques (Macaca
      fascicularis) in Peninsular Malaysia, a widely used non-human primate species in
      biomedical research, have not been thoroughly characterized. METHODS: Thirteen
      sites of wild populations of long-tailed macaques representing six states were
      sampled and analyzed with 18 STR markers. RESULTS: The Sunggala and Penang Island
      populations showed the highest genetic diversity estimates, while the Jerejak
      Island population was the most genetically discrete due to isolation from the
      mainland shelf. Concordant with pairwise F(st) estimates, STRUCTURE analyses of
      the seven PCA-correlated clusters revealed low to moderate differentiation among
      the sampling sites. No association between geographic and genetic distances
      exists, suggesting that the study sites, including island study sites, are
      genetically if not geographically contiguous. CONCLUSIONS: The status of the
      genetic structure and composition of long-tailed macaque populations require
      further scrutiny to develop this species as an important animal model in
      biomedical research.

PMID- 24930738
TI  - Surfactants in the sea-surface microlayer and atmospheric aerosol around the
      southern region of Peninsular Malaysia.
AB  - This study was conducted to determine the composition of surfactants in the sea
      surface microlayer (SML) and atmospheric aerosol around the southern region of
      the Peninsular Malaysia. Surfactants in samples taken from the SML and
      atmospheric aerosol were determined using a colorimetric method, as either
      methylene blue active substances (MBAS) or disulphine blue active substances
      (DBAS). Principal component analysis with multiple linear regressions (PCA-MLR),
      using the anion and major element composition of the aerosol samples, was used to
      determine possible sources of surfactants in atmospheric aerosol. The results
      showed that the concentrations of surfactants in the SML and atmospheric aerosol
      were dominated by anionic surfactants and that surfactants in aerosol were not
      directly correlated (p>0.05) with surfactants in the SML. Further PCA-MLR from
      anion and major element concentrations showed that combustion of fossil fuel and
      sea spray were the major contributors to surfactants in aerosol in the study
      area. 

PMID- 24930737
TI  - Heavy metal contamination and ecological risk in Spartina alterniflora marsh in
      intertidal sediments of Bohai Bay, China.
AB  - To investigate the effects of Spartina alterniflora on heavy metals pollution of
      intertidal sediments, sediment cores of a S. alterniflora salt marsh and a
      mudflat in Bohai Bay, China were analyzed. The results showed that S.
      alterniflora caused higher total C and P, but lower bulk density and electrical
      conductivity. The levels of Cd, Cu and Pb were higher in S. alterniflora
      sediment. Both Cd and Zn were higher than the probable effect level at both
      sites, indicating their toxicological importance. The geo-accumulation and
      potential ecological risk indexes revealed higher metal contamination in S.
      alterniflora sediment. Multivariate analysis implied that anthropogenic
      activities altered mobility and bioavailability of heavy metals. The percentage
      of mobile heavy metals was higher in S. alterniflora sediment, indicating
      improvement of conversion from the immobilized fraction to the mobilized
      fraction. These findings indicate that S. alterniflora may facilitate
      accumulation of heavy metals and increase their bioavailability and mobility. 

PMID- 24930739
TI  - Quantities, composition, and sources of beach debris in Korea from the results of
      nationwide monitoring.
AB  - This study assessed the levels of marine debris pollution and identified its main
      sources in Korea. The surveys were bimonthly conducted by NGO leaders and
      volunteers on 20 beaches from March 2008 to November 2009. The quantities of
      marine debris were estimated at 480.9 (+/-267.7) count?100 m(-1) for number, 86.5
      (+/-78.6) kg?100 m(-1) for weight, and 0.48 (+/-0.38) m(3)?100 m(-1) for volume.
      The level of marine debris pollution on the Korean beaches was comparable to that
      in the coastal areas of the North Atlantic ocean and South Africa. Plastics and
      styrofoam occupied the majority of debris composition in terms of number (66.7%)
      and volume (62.3%). The main sources of debris were fishing activities including
      commercial fisheries and marine aquaculture (51.3%). Especially styrofoam buoy
      from aquaculture was the biggest contributor to marine debris pollution on these
      beaches.

PMID- 24930740
TI  - The use of botulinum toxin in otorhinolaryngology: an updated review.
AB  - BACKGROUND: The use of botulinum toxin in Otorhinolaryngology has rapidly
      expanded over the last decade. Current observation is that the use of botulinum
      toxin in Otorhinolaryngology is relatively poorly acknowledged by
      Otorhinolaryngologists. OBJECTIVE OF REVIEW: To summarise the non-cosmetic uses
      of botulinum toxin in Otorhinolaryngology. TYPE OF REVIEW: Narrative. SEARCH
      STRATEGY AND EVALUATION METHOD: A literature search was performed using the
      Medline and Embase databases. Combinations of 'botulinum toxin' with each
      indication were searched. A citation was included if it evaluated a non-cosmetic
      use of botulinum toxin in Otorhinolaryngology. Eligibility of studies was
      assessed by two reviewers. A total of 1187 abstracts were reviewed and 97
      articles identified. CONCLUSIONS: Botulinum toxin provides an effective and
      minimally invasive treatment option in a wide range of non-cosmetic indications.
      Side-effects are few and transient with an excellent safety profile. Ongoing
      research is required to fully critically appraise its uses.

PMID- 24930741
TI  - Virus particle assembly into crystalline domains enabled by the coffee ring
      effect.
AB  - Tobacco mosaic virus particles can be rapidly assembled into 3D-domains by
      capillary flow-driven alignment at the triple contact-line of an evaporating
      droplet. Virus particles of ~150 A diameter can be resolved within individual
      domains at the outer rim of the "coffee-ring" type residue by atomic force
      microscopy. The crystalline domains can also be probed by X-ray microdiffraction
      techniques. Both techniques reveal that the rod-like virus particles are oriented
      parallel to the rim. We further demonstrate the feasibility of collection of hk0
      reflection intensities in GISAXS geometry and show it allows calculating a low
      resolution electron density projection along the rod axis. 

PMID- 24930743
TI  - Two CCAAT-box-binding transcription factors redundantly regulate early steps of
      the legume-rhizobia endosymbiosis.
AB  - During endosymbiotic interactions between legume plants and nitrogen-fixing
      rhizobia, successful root infection by bacteria and nodule organogenesis requires
      the perception and transduction of bacterial lipo-chitooligosaccharidic signal
      called Nod factor (NF). NF perception in legume roots leads to the activation of
      an early signaling pathway and of a set of symbiotic genes which is controlled by
      specific early transcription factors (TFs) including CYCLOPS/IPD3, NSP1, NSP2,
      ERN1 and NIN. In this study, we bring convincing evidence that the Medicago
      truncatula CCAAT-box-binding NF-YA1 TF, previously associated with later stages
      of rhizobial infection and nodule meristem formation is, together with its
      closest homolog NF-YA2, also an essential positive regulator of the NF-signaling
      pathway. Here we show that NF-YA1 and NF-YA2 are both expressed in epidermal
      cells responding to NFs and their knock-down by reverse genetic approaches
      severely affects the NF-induced expression of symbiotic genes and rhizobial
      infection. Further over-expression, transactivation and ChIP-PCR approaches
      indicate that NF-YA1 and NF-YA2 function, at least in part, via the direct
      activation of ERN1. We thus propose a model in which NF-YA1 and NF-YA2 appear as
      early symbiotic regulators acting downstream of DMI3 and NIN and possibly within
      the same regulatory complexes as NSP1/2 to directly activate the expression of
      ERN1. 

PMID- 24930745
TI  - Antimicrobial efficacy of chlorhexidine as a root canal irrigant: a literature
      review.
AB  - Use of an appropriate root canal irrigant is essential during endodontic
      treatment, due to the complex and unpredictable anatomy of the root canal system
      and limitations in the mechanical instrumentation techniques used to obtain a
      clean, bacteria-free canal. Several irrigants, such as sodium hypochlorite,
      chlorhexidine, hydrogen peroxide, and normal saline, have been proposed as canal
      system irrigants in endodontic treatment. The widely used endodontic irrigant
      chlorhexidine is a positively charged lipophilic/hydrophobic molecule that
      interacts with phospholipids and lipopolysaccharides on the bacterial cell
      membrane. In endodontics, its mode of antibacterial activity is determined by its
      concentration (0.2% or 2%). This article reviews findings from available
      endodontic studies on the antibacterial, antifungal, and antibiofilm activities
      of chlorhexidine.

PMID- 24930744
TI  - Periodontal status and serum biomarkers levels in haemodialysis patients.
AB  - AIM: To investigate the association between periodontal status and serum
      biomarkers levels in haemodialysis patients. METHODS: This cross-sectional study
      included 96 haemodialysis patients. The periodontal evaluation was realized using
      clinical attachment level (CAL), probing depth (PD), gingival bleeding index
      (GBI), visible plaque index (VPI) and gingival index (GI). Biochemical and
      haematological data - serum albumin, phosphorus, creatinine, transferrin,
      ferritin, iron, alkaline phosphatase, calcium, potassium and haemoglobin - were
      collected from the medical records. The subject was diagnosed with periodontitis
      if he/she had at least two inter-proximal sites in different teeth with CAL >=4
      mm and/or at least two inter-proximal sites in separate teeth with PD >=5 mm.
      RESULTS: The study population consisted of 45 men and 51 women, with mean time
      under haemodialysis of 45.6 +/- 33.1 months. Periodontitis was observed in 59.4%
      of the subjects. The periodontitis group had albumin (p = 0.021) and phosphorus
      (p = 0.024) serum levels lower than the no periodontitis group. Thus, there was a
      positive association of periodontitis with hypoalbuminaemia (OR = 9.10, p =
      0.006) and a negative association with hyperphosphataemia (OR = 0.21, p = 0.010).
      CONCLUSIONS: These findings suggest that periodontitis is associated with albumin
      and phosphorus serum levels in haemodialysis patients.

PMID- 24930746
TI  - Effect of gutta-percha solvents on fiberglass post bond strength to root canal
      dentin.
AB  - The purpose of this study was to investigate the influence of gutta-percha
      solvents on the bond strength of fiberglass post to root canal dentin. Forty
      bovine incisors were decoronated, prepared, filled, and randomly distributed into
      four groups (n = 10) according to the gutta-percha solvent used: control, xylene,
      eucalyptol and orange oil. After root canal treatment, the posts were cemented
      into the prepared root canals using a resin-based cement. A micro push-out test
      was executed, and the patterns of failure were assessed with microscopy. The data
      were analyzed using two-way ANOVA followed by Tukey's test. The control group
      exhibited greater bond strength compared to the eucalyptol group in the cervical
      and middle thirds of the root (P < 0.05); however, it did not differ
      significantly from the xylene and orange oil groups (P > 0.05). No difference was
      observed in the values of the xylene, orange oil, and eucalyptol groups (P >
      0.05). The cervical third had higher values than the apical third for all tested
      solvents (P < 0.05). Adhesive failure between resin cement and dentin was the
      most frequent type of failure. The use of xylene and orange oil as gutta-percha
      solvents did not influence the bond strength of fiberglass posts to root canal
      dentin.

PMID- 24930747
TI  - A healing period increases mini-implant stability in growing rats.
AB  - We assessed the stability of orthodontic mini-implants in young rats. Male rats
      with mean ages of 6 weeks (n = 16) and 20 weeks (n = 16) were divided into four
      groups (n = 8 each). In the 6- and 20-week immediate-loading groups, immediately
      after placement, mini-implants were exposed to an experimental traction force for
      2 weeks. In the 6- and 20-week healing groups, the force was applied for 2 weeks
      after a 6-week healing period. Right tibiae served as the test limbs and the left
      tibiae as controls. A Periotest device was used to measure mini-implant mobility
      after traction, and Tukey's test was used to compare Periotest values among
      groups. The results showed significantly greater mobility in the 6-week immediate
      loading group than in the 20-week immediate-loading and 6- and 20-week healing
      groups, and significantly less mobility in the 6-week healing group than in the
      20-week immediate-loading group (P < 0.05). Mini-implants were stable during the
      healing period. The results indicate that mini-implants can be used for
      orthodontic anchorage in juvenile patients if the duration of healing is
      sufficient.

PMID- 24930748
TI  - Chitosan exerts anticancer activity through induction of apoptosis and cell cycle
      arrest in oral cancer cells.
AB  - Chitosan, a multipurpose biomaterial, has been shown to exert effects against
      several types of cancer including oral cancer. However, the mechanisms underlying
      the anticancer activities of chitosan on oral squamous cell carcinoma (SCC) cells
      remain largely unknown. The present study aimed to compare the effects of low
      molecular-weight chitosan (LMWC) and cisplatin on oral SCC Ca9-22 and non-cancer
      keratinocyte HaCaT cell lines. Cell viability and cell cycle profiles were
      measured by MTT assay and laser scanning cytometry, respectively. Apoptosis was
      examined by TUNEL assay and electron microscopy, followed by analysis of caspase
      activity. LMWC exhibited cytotoxic effects on Ca9-22, but not HaCaT cells,
      whereas cisplatin induced apoptosis in both types of cells. Exposure of Ca9-22
      cells to LMWC led to G1/S cell cycle arrest and an increase of TUNEL-positive
      cells accompanied by an early apoptotic cell morphology and subtle increases of
      caspase activity. Short-term LMWC exposure was less cytotoxic to HaCaT cells than
      to Ca9-22 cells, and anticancer activity was exerted through induction of
      apoptosis and cell cycle arrest, suggesting that LMWC could be a promising
      natural anticancer agent with fewer side effects on normal cells.

PMID- 24930749
TI  - Association of temporomandibular disorder symptoms with anxiety and depression in
      Portuguese college students.
AB  - We investigated the prevalence of temporomandibular disorder (TMD) and its
      association with anxiety and depression among 1,493 Portuguese college students
      (age 17-69 years) at Piaget Institute. The assessment instruments were the
      Fonseca Anamnestic Questionnaire and the Hospital Anxiety and Depression Scale.
      TMD was present in 633 (42.4%) students, and anxiety or depression was present in
      456 (30.5%) students. Regarding the association of TMD with anxiety and
      depression, 280 of the 633 students (61.4%) with TMD symptoms also had signs of
      anxiety or depression (P < 0.001). As compared with men, women had an odds ratio
      of 1.9 (95% confidence interval: 1.53-2.46; P < 0.001) for TMD. As compared with
      students without signs of anxiety or depression, students with such signs had an
      odds ratio of 3.1 (95% confidence interval: 2.42-3.84; P < 0.001) for TMD.
      College students from various fields of study and regions of Portugal had a high
      prevalence of TMD, which was significantly associated with anxiety and
      depression.

PMID- 24930750
TI  - Evaluation of salivary and serum lipid peroxidation, and glutathione in oral
      leukoplakia and oral squamous cell carcinoma.
AB  - Lipid peroxidation induced by reactive oxygen species (ROS) is involved in the
      pathogenesis of malignancy. Overall, lipid peroxidation levels are indicated by
      malondialdehyde (MDA), which is the most frequently used biomarker to detect
      oxidative changes. Antioxidant defense systems such as glutathione (GSH) limit
      cell injury induced by ROS. Therefore, MDA and GSH can be used to monitor
      oxidative stress (OS). Hence, this study aimed to evaluate and compare both
      salivary and serum levels of MDA and GSH in oral leukoplakia and oral squamous
      cell carcinoma (OSCC) patients, and healthy controls. The study included 100
      subjects comprising 30 apparently healthy controls, 30 patients with oral
      leukoplakia and 40 clinically and histologically diagnosed patients with OSCC.
      Saliva and blood samples were obtained and evaluated for MDA and GSH. The study
      revealed enhanced MDA levels in saliva and serum in oral leukoplakia and OSCC
      patients as compared to controls. On the other hand, significant decreases were
      seen in serum and salivary GSH levels in oral leukoplakia and OSCC patients as
      compared to controls. Augmentation of OS in blood and saliva is reflected by
      increase in MDA and decrease in GSH levels, indicating that tumor processes cause
      an imbalance of oxidant-antioxidant status in cell structures.

PMID- 24930751
TI  - Associations of clinical characteristics and interval between maintenance visits
      with peri-implant pathology.
AB  - We investigated the effects of clinical characteristics and the interval between
      maintenance visits on incidence of peri-implant pathology in a sample of 1,350
      patients treated with dental implants (270 cases of peri-implant pathology and
      1,080 healthy controls). The chi-square test was used to evaluate differences
      between cases and controls in the presence of dental plaque, bleeding, peri
      implant pockets >4 mm, bone level, and interval between maintenance visits
      (significance level, 5%). Crude odds ratios (ORs) and attributable fractions were
      calculated for variables that significantly differed between cases and controls.
      The variables identified as risk indicators were dental plaque (P < 0.001; OR =
      5.2), bleeding (P < 0.001; OR = 5.0), peri-implant pockets >4 mm (P < 0.001; OR =
      17.2), bone level (P < 0.001; middle third, OR = 8.4; apical third, OR = 8.6),
      and interval between maintenance visits (P < 0.001; 1-3 months, OR = 2.9; 3-5
      months, OR = 2.1). Attributable fractions revealed a potential reduction in peri
      implant pathology of 53-94% after removing exposures to dental plaque (81%),
      bleeding (80%), peri-implant pockets >4 mm (94%), bone level (88%), and interval
      between maintenance visits (53-66%). Selected clinical characteristics and the
      interval between maintenance visits were significantly associated with the
      incidence of peri-implant pathology.

PMID- 24930752
TI  - Utility and validity of a single-item visual analog scale for measuring dental
      anxiety in clinical practice.
AB  - We evaluated whether a visual analog scale (VAS) was comparable to the multi-item
      Modified Dental Anxiety Scale (MDAS) in assessing dental anxiety in clinical
      practice. In total, 200 consecutive patients aged 20-70 years who presented at
      the dental outpatient department of SRM Dental College, Chennai were enrolled.
      The test-retest value for the VAS was 0.968. The Spearman rank correlations
      between the VAS and MDAS items and total score were significant (P < 0.001). The
      Spearman rank correlation between postponement of a dental visit and the VAS also
      showed a strong correlation (r = 0.473, P < 0.001). On linear regression
      analysis, the coefficient of determination showed a strong relationship between
      the two variables; the MDAS accounted for 74% of the variation. The regression
      coefficient was statistically significant (P < 0.001). On the basis of receiver
      operating-characteristic curve analysis, a VAS cut-off value of >=4.8 was
      selected to discriminate between patients who were and were not anxious, and a
      cut-off value of >=7 was selected to identify patients with dental phobia. The
      weighted kappa was 69% for agreement between MDAS and the VAS in identifying
      patients with and without dental anxiety at cut-offs of 13 and 4.75,
      respectively. The VAS was found to be a valid measure and was comparable to the
      multi-item MDAS.

PMID- 24930753
TI  - MicroRNA-146a and microRNA-155 show tissue-dependent expression in dental pulp,
      gingival and periodontal ligament fibroblasts in vitro.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs showing a tissue-specific expression
      pattern, and whose function is to suppress protein synthesis. In this study, we
      hypothesized that expression of miRNAs would differ among fibroblasts from dental
      pulp (DPF), gingiva (GF) and periodontal ligament (PLF) in vitro. Once
      established by an explant technique, DPF, GF and PLF were collected for RNA
      isolation and subjected to a miRNA microarray. Next, cells were stimulated with
      E. coli lipopolysaccharide (LPS) for 24 h and then collected for RNA isolation.
      Expression of miR-146a and miR-155 was investigated by qPCR. Microarray screening
      revealed several miRNAs that showed specifically high expression in at least one
      of the fibroblast subtypes. These molecules are potentially involved in the
      regulation of extracellular matrix turnover and production of inflammatory
      mediators. Microarray analysis showed that both miR-146a and miR-155 were among
      the miRNAs expressed exclusively in GF. qPCR demonstrated significant
      upregulation of miR-146a only in GF after LPS stimulation, whereas basal
      expression of miR-155 was higher in GF than in the other cell subtypes. LPS
      downregulated the expression of miR-155 only in GF. Our results suggest that the
      expression and regulation of miR-146a and miR-155 are more pronounced in GF than
      in DPF and PLF.

PMID- 24930754
TI  - Three-dimensional craniofacial morphology in unilateral cleft lip and palate.
AB  - Craniofacial morphology and asymmetry were compared before, during, and after
      puberty within and between patients with unilateral complete cleft lip and palate
      (UCCLP) and a non-cleft group. In the UCCLP group, the posterior cranial base and
      total cranial base were significantly shorter at all skeletal periods, the
      maxilla was significantly retruded and posteriorly rotated, and the mandible was
      significantly smaller and inferoposteriorly rotated. The angle between the nasal
      and mandibular plane and lower anterior facial height were significantly higher,
      and upper posterior facial height and total posterior height were significantly
      lower, in the UCCLP group. Except for an increase in the nasal cavity, no
      significant differences were detected in facial width. For all measurements,
      asymmetry on the horizontal plane was more significant than that on the vertical
      plane. Asymmetries in the UCCLP group were mostly detected during puberty. The
      UCCLP group had no distinctive mandibular asymmetry, as compared with the Class I
      group. In UCCLP patients, the cranial base, maxilla, and mandible were affected
      on the sagittal plane during all growth periods. However, horizontal asymmetries
      were mostly detected before and during puberty. Vertical asymmetries were less
      severe, and there was no distinctive mandibular asymmetry as compared with the
      Class I group. (J Oral Sci 56, 165-172, 2014). 

PMID- 24930755
TI  - Morphometric analysis of the mucosal vasculature in oral submucous fibrosis and
      its comparison with oral squamous cell carcinoma.
AB  - Oral submucous fibrosis (OSMF) is a chronic fibrotic disorder in which the degree
      of vascularity has always been a matter of dispute; however, morphological
      studies of the blood vessels in OSMF have been sparse. This study was performed
      to assess the mucosal vasculature in normal oral mucosa, early and advanced OSMF,
      and well differentiated squamous cell carcinoma (WDSCC) using morphometry. The
      study included histologically diagnosed cases of early (n = 30) and advanced (n =
      30) OSMF, and WDSCC (n = 30), with normal oral mucosa (n = 10) as a control.
      Morphometric image analysis of blood vessels was performed on H&E-stained
      sections for evaluation of vascular density, vascular luminal diameter, area and
      percentage area. A significant increase in all of the parameters was noted in the
      test groups relative to the controls. The mean vascular density and mean vascular
      percentage area were significantly increased in early OSMF and WDSCC relative to
      controls, and also in advanced OSMF and WDSCC in comparison with early OSMF. The
      vascularity increased progressively from normal to premalignancy and malignancy,
      emphasizing the importance of angiogenesis in tumor development and progression.
      The vascularity was increased in early OSMF and reduced in advanced OSMF,
      suggesting that inflammation may play a role in the early stages while
      progressive fibrosis may predispose to atrophy of the epithelium and subsequent
      malignant changes.

PMID- 24930756
TI  - Technical complications with implant-supported dental prostheses.
AB  - Studies are needed to determine the prognosis of different forms of dental
      prosthetic rehabilitation and the main complications involved. The purpose of the
      present study was to evaluate technical complications involving implant-supported
      prostheses. A retrospective one time snap-shot study was carried out with a total
      of 509 implants in 153 patients. Prosthetic conditions were determined by
      clinical and radiographic examination. The least frequent technical complication
      involved fracture (0.2%), loss (0.4%) and loosening (3.3%) of the screw. The most
      frequent complications were loss of resin covering the screw (23.8%), loss of
      overdenture retention (18.6%) and fractures of the resin (12.4%). A high
      frequency of misfit between the prosthesis and abutment (25.4%) was found, which
      was significantly associated (P < 0.05) with other variables, especially cemented
      prostheses (P < 0.001). To minimize the frequency of complications, protocols
      must be established from diagnosis to the completion of treatment and follow up
      of implant-supported prostheses, especially in terms of adequate technical steps
      and careful radiographic evaluation of the components.

PMID- 24930757
TI  - Ilimaquinone induces death receptor expression and sensitizes human colon cancer
      cells to TRAIL-induced apoptosis through activation of ROS-ERK/p38 MAPK-CHOP
      signaling pathways.
AB  - TRAIL induces apoptosis in a variety of tumor cells. However, development of
      resistance to TRAIL is a major obstacle to more effective cancer treatment.
      Therefore, novel pharmacological agents that enhance sensitivity to TRAIL are
      necessary. In the present study, we investigated the molecular mechanisms by
      which ilimaquinone isolated from a sea sponge sensitizes human colon cancer cells
      to TRAIL. Ilimaquinone pretreatment significantly enhanced TRAIL-induced
      apoptosis in HCT 116 cells and sensitized colon cancer cells to TRAIL-induced
      apoptosis through increased caspase-8, -3 activation, PARP cleavage, and DNA
      damage. Ilimaquinone also reduced the cell survival proteins Bcl2 and Bcl-xL,
      while strongly up-regulating death receptor (DR) 4 and DR5 expression. Induction
      of DR4 and DR5 by ilimaquinone was mediated through up-regulation of
      CCAAT/enhancer-binding protein homologous protein (CHOP). The up-regulation of
      CHOP, DR4 and DR5 expression was mediated through activation of extracellular
      signal regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK)
      signaling pathways. Finally, the generation of ROS was required for CHOP and DR5
      up-regulation by ilimaquinone. These results demonstrate that ilimaquinone
      enhanced the sensitivity of human colon cancer cells to TRAIL-induced apoptosis
      through ROS-ERK/p38 MAPK-CHOP-mediated up-regulation of DR4 and DR5 expression,
      suggesting that ilimaquinone could be developed into an adjuvant chemotherapeutic
      drug. 

PMID- 24930758
TI  - Disturbed Hsp70 and Hsp27 expression and thiol redox status in porcine kidney
      PK15 cells provoked by individual and combined ochratoxin A and citrinin
      treatments.
AB  - The aim of this study was to explore the oxidative properties of ochratoxin A
      (OTA) and citrinin (CTN) as a possible underlying mechanism of their individual
      and/or combined cytotoxicity. Metabolic activity of PK15 porcine kidney cells was
      significantly reduced with OTA and CTN co-exposures, with synergistic cytotoxic
      interactions. Single CTN increased both reduced (GSH) and oxidized (GSSG)
      glutathione after 24 h. However, GSH was significantly lowered with all OTA and
      CTN combined applications in synergistic manner after 12 and 24 h. GSH/GSSG ratio
      was reduced in most single and dual treatments, which suggested the presence of
      oxidative stress. In addition, OTA and CTN exposures significantly decreased
      concentrations of total thiols, with mycotoxins interactions being synergistic or
      antagonistic. The expression levels of Hsps were differentially affected by
      single and dual mycotoxin(s) applications. Single OTA provoked significant down
      regulation of Hsp70 and Hsp27 expressions, while CTN stimulated Hsps expressions.
      Hsps were also up-regulated by dual treatments, and this induction was much
      stronger then with single CTN. In conclusion, significant alterations in cellular
      redox status (glutathione, thiols) and protective mechanisms (Hsps) suggest that
      those disturbances might be involved in OTA and CTN individual and combined
      mechanisms of cytotoxicity.

PMID- 24930759
TI  - Successful treatment of non-Hodgkin's lymphoma using R-CHOP in a patient with
      Wiskott-Aldrich syndrome followed by a reduced-intensity stem cell transplant.
AB  - WAS is an X-linked primary immunodeficiency characterized by
      microthrombocytopenia, eczema, recurrent infections, and increased incidence of
      autoimmunity and malignancy. HSCT is the only curative treatment for WAS. Herein,
      we report the case of a 17-yr-old boy with WAS who received an unrelated HSCT
      while in complete remission of diffuse large B-cell lymphoma after chemotherapy.
      Pretransplant conditioning consisted of fludarabine, busulfan, and total body
      irradiation (4 Gy). GvHD prophylaxis consisted of tacrolimus and short-course
      methotrexate. Following HSCT, rapid and stable engraftment was observed. Platelet
      count gradually increased, and the generalized eczema improved. The patient
      developed grade II acute GvHD and limited chronic GvHD on days 30 and 210,
      respectively, which resolved with immunosuppressive treatment. Symptoms caused by
      the reactivation of human herpes virus-6, BK virus, and VZV were observed from
      days 21, 60, and 96, respectively; they were resolved after conservative
      treatment and acyclovir administration. No other regimen-related toxicity was
      observed. Complete donor bone marrow chimerism was achieved one month after
      transplantation. RIST is an effective therapeutic option for older children with
      WAS accompanied by malignant lymphoma. 

PMID- 24930760
TI  - Left atrial asynchrony and mechanical function in patients with mitral stenosis
      before and immediately after percutaneous balloon mitral valvuloplasty: a real
      time three-dimensional echocardiography study.
AB  - OBJECTIVE: This study evaluated the feasibility of assessing left atrium (LA)
      function and asynchrony in patients with rheumatic mitral stenosis (MS) before
      and immediately after percutaneous balloon mitral valvuloplasty (PBMV) by real
      time three-dimensional echocardiography (RT3DE). METHODS: Thirty patients with
      rheumatic MS who underwent PBMV and 30 controls were enrolled. RT3DE was used to
      measure LA volume and function, the standard deviation of time to the minimal
      systolic volume divided into 16 segments, 12 segments, or 6 segments (Tmsv 16-SD,
      Tmsv 12-SD, Tmsv 6-SD), and the maximum differences (Tmsv 16-Dif, 12-Dif, 6-Dif)
      in RT3DE derived values in MS patients before and 2 days after PBMV were obtained
      and compared with those of normal controls. The associations between the LA
      asynchrony and heart volume, function, mitral valve area (MVA), maximum mitral
      valve gradient (MVGmax ), mean mitral valve gradient (MVGmean), and mean LA
      pressure (MLAP) were investigated. RESULTS: Left atrium asynchrony indexes were
      significantly larger, and LA function parameters were significantly lower in the
      MS group than in the controls (P < 0.05 for all). Of all the LA asynchrony
      indexes, LA Tmsv16-SD was most significantly correlated with the LA volume and
      function parameters, MVGmax , MVGmean , and MLAP (P < 0.05 for all). LA
      asynchrony indexes and LA volume significantly deceased, and LA function
      significantly increased post-PBMV (P < 0.05). CONCLUSION: Real time three
      dimensional echocardiography is a reliable and reproducible method to quantify LA
      function and asynchrony. RT3DE revealed a significant, early improvement in LA
      function and asynchrony in MS patients after PBMV.

PMID- 24930761
TI  - [VENTILOP survey. Survey in peroperative mechanical ventilation].
AB  - INTRODUCTION: Mechanical ventilation can initiate ventilator-associated lung
      injury and postoperative pulmonary complications. The aim of this study was to
      evaluate (1) how mechanical ventilation was comprehended by anaesthetists
      (physician and nurses) and (2) the need for educational programs. METHODS: A
      computing questionnary was sent by electronic-mail to the entire anaesthetist
      from Alsace region in France (297 physicians), and to a pool of 99 nurse
      anaesthetists. Mechanical ventilation during anaesthesia was considered as
      optimized when low tidal volume (6-8mL) of ideal body weight was associated with
      positive end expiratory pressure, FiO2 less than 50%, I/E adjustment and
      recruitment maneuvers. RESULTS: The participation rate was 50.5% (172
      professionals). Only 2.3% of professionals used the five parameters for optimized
      ventilation. Majority of professionals considered that mechanical ventilation
      adjustment influenced the patients' postoperative outcome. Majority of the
      professionals asked for a specific educational program in the field of mechanical
      ventilation. DISCUSSION: Only 2.3% of professionals optimized mechanical
      ventilation during anaesthesia. Guidelines and specific educational programs in
      the field of mechanical ventilation are widely expected.

PMID- 24930762
TI  - [Storing succinylcholine in prehospital settings following the recommendations of
      the French National Agency for the safety of medicines].
AB  - OBJECTIVE: The French National Pharmaceuticals Agency (ANSM) has recommanded in
      July 2012 not to break the cold chain before using succinylcholine
      (Celocurine(r)). RESEARCH OBJECTIVE: to understand the pre-clinical evolution of
      the conservation modes of this curare. RESEARCH TYPE: Descriptive study before
      (year 2011) and after (year 2012). PATIENTS AND METHOD: Online survey to French
      Samu/Smur. DATA COLLECTED: SMUR location, conservation method at clinical base,
      in the mobile unit (UMH) and at the patient. Principal decision criteria:
      evolution of the conservation modes before and after the recommendation
      (qualitatives variables compared with a Fisher test). RESULTS: Out of 101
      SAMU/SMUR, 62 answered. Conservation modes of succinylcholine vials were
      significantly different (P<0.001). Proper conservation was observed in 26 % of
      the cases before and 43 % after. Mobile units (UMH) equipped with a fridge
      increased from one out of two to 77 %. The lack of conservation modes passive or
      active on UMH went from 31 % to 3.4 % with isotherms bags with ice when a fridge
      was not available. The destruction of capsules at current temperature in a 24
      hour period increased: 22 % before, 47 % after (P=0.04). CONCLUSION: After
      recommendations from ANSM, conservation modes and destruction of succinylcholine
      in a prehospital environment were significantly impacted.

PMID- 24930763
TI  - Phase transformation of cadmium sulfide under high temperature and high pressure
      conditions.
AB  - Cadmium sulfide (CdS) is one of the most significant wide band gap
      semiconductors, and knowledge of the phase transformation of CdS under high
      temperature and pressure is especially important for its applications. The
      pressure-temperature phase diagram and the phase transformation pathways of CdS
      have been investigated by using density functional theory combined with
      quasiharmonic approximation. Our results indicated that under ambient conditions,
      wz-CdS is a stable phase, while under high temperature and pressure, rs-CdS
      becomes the stable phase. It is also found that zb-CdS is an intermediate phase
      in transforming from rs-CdS to wz-CdS. Therefore, although there are no zb-CdS
      phase regions in the CdS pressure-temperature phase diagram, zb-CdS can be found
      in some prepared experiments. 

PMID- 24930764
TI  - ROS-mediated EB1 phosphorylation through Akt/GSK3beta pathway: implication in
      cancer cell response to microtubule-targeting agents.
AB  - Microtubule-targeting agents (MTAs) are largely administered in adults and
      children cancers. Better deciphering their mechanism of action is of prime
      importance to develop more convenient therapy strategies. Here, we addressed the
      question of how reactive oxygen species (ROS) generation by mitochondria can be
      necessary for MTA efficacy. We showed for the first time that EB1 associates with
      microtubules in a phosphorylation-dependent manner, under control of ROS. By
      using phospho-defective mutants, we further characterized the Serine 155 residue
      as critical for EB1 accumulation at microtubule plus-ends, and both cancer cell
      migration and proliferation. Phosphorylation of EB1 on the Threonine 166 residue
      triggered opposite effects, and was identified as a requisite molecular switch in
      MTA activities. We then showed that GSK3beta activation was responsible for MTA
      triggered EB1 phosphorylation, resulting from ROS-mediated inhibition of upstream
      Akt. We thus disclosed here a novel pathway by which generation of mitochondrial
      ROS modulates microtubule dynamics through phosphorylation of EB1, improving our
      fundamental knowledge about this oncogenic protein, and pointing out the need to
      re-examine the current dogma of microtubule targeting by MTAs. The present work
      also provides a strong mechanistic rational to the promising therapeutic
      strategies that currently combine MTAs with anti-Akt targeted therapies. 

PMID- 24930765
TI  - Historical contingency and its biophysical basis in glucocorticoid receptor
      evolution.
AB  - Understanding how chance historical events shape evolutionary processes is a
      central goal of evolutionary biology. Direct insights into the extent and causes
      of evolutionary contingency have been limited to experimental systems, because it
      is difficult to know what happened in the deep past and to characterize other
      paths that evolution could have followed. Here we combine ancestral protein
      reconstruction, directed evolution and biophysical analysis to explore
      alternative 'might-have-been' trajectories during the ancient evolution of a
      novel protein function. We previously found that the evolution of cortisol
      specificity in the ancestral glucocorticoid receptor (GR) was contingent on
      permissive substitutions, which had no apparent effect on receptor function but
      were necessary for GR to tolerate the large-effect mutations that caused the
      shift in specificity. Here we show that alternative mutations that could have
      permitted the historical function-switching substitutions are extremely rare in
      the ensemble of genotypes accessible to the ancestral GR. In a library of
      thousands of variants of the ancestral protein, we recovered historical
      permissive substitutions but no alternative permissive genotypes. Using
      biophysical analysis, we found that permissive mutations must satisfy at least
      three physical requirements--they must stabilize specific local elements of the
      protein structure, maintain the correct energetic balance between functional
      conformations, and be compatible with the ancestral and derived structures--thus
      revealing why permissive mutations are rare. These findings demonstrate that GR
      evolution depended strongly on improbable, non-deterministic events, and this
      contingency arose from intrinsic biophysical properties of the protein.

PMID- 24930767
TI  - Normal-state nodal electronic structure in underdoped high-Tc copper oxides.
AB  - An outstanding problem in the field of high-transition-temperature (high-Tc)
      superconductivity is the identification of the normal state out of which
      superconductivity emerges in the mysterious underdoped regime. The normal state
      uncomplicated by thermal fluctuations can be studied using applied magnetic
      fields that are sufficiently strong to suppress long-range superconductivity at
      low temperatures. Proposals in which the normal ground state is characterized by
      small Fermi surface pockets that exist in the absence of symmetry breaking have
      been superseded by models based on the existence of a superlattice that breaks
      the translational symmetry of the underlying lattice. Recently, a charge
      superlattice model that positions a small electron-like Fermi pocket in the
      vicinity of the nodes (where the superconducting gap is minimum) has been
      proposed as a replacement for the prevalent superlattice models that position the
      Fermi pocket in the vicinity of the pseudogap at the antinodes (where the
      superconducting gap is maximum). Although some ingredients of symmetry breaking
      have been recently revealed by crystallographic studies, their relevance to the
      electronic structure remains unresolved. Here we report angle-resolved quantum
      oscillation measurements in the underdoped copper oxide YBa2Cu3O6 + x. These
      measurements reveal a normal ground state comprising electron-like Fermi surface
      pockets located in the vicinity of the nodes, and also point to an underlying
      superlattice structure of low frequency and long wavelength with features in
      common with the charge order identified recently by complementary spectroscopic
      techniques. 

PMID- 24930768
TI  - Raman spectroscopy explores molecular structural signatures of hidden materials
      in depth: Universal Multiple Angle Raman Spectroscopy.
AB  - Non-invasive 3D imaging in materials and medical research involves methodologies
      such as X-ray imaging, MRI, fluorescence and optical coherence tomography, NIR
      absorption imaging, etc., providing global morphological/density/absorption
      changes of the hidden components. However, molecular information of such buried
      materials has been elusive. In this article we demonstrate observation of
      molecular structural information of materials hidden/buried in depth using Raman
      scattering. Typically, Raman spectroscopic observations are made at fixed
      collection angles, such as, 90 degrees , 135 degrees , and 180 degrees , except
      in spatially offset Raman scattering (SORS) (only back scattering based
      collection of photons) and transmission techniques. Such specific collection
      angles restrict the observations of Raman signals either from or near the surface
      of the materials. Universal Multiple Angle Raman Spectroscopy (UMARS) presented
      here employs the principle of (a) penetration depth of photons and then diffuse
      propagation through non-absorbing media by multiple scattering and (b) detection
      of signals from all the observable angles. 

PMID- 24930766
TI  - Aryl hydrocarbon receptor control of a disease tolerance defence pathway.
AB  - Disease tolerance is the ability of the host to reduce the effect of infection on
      host fitness. Analysis of disease tolerance pathways could provide new approaches
      for treating infections and other inflammatory diseases. Typically, an initial
      exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness
      to further LPS challenge (endotoxin tolerance). We found that a first exposure of
      mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon
      receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided
      an activating ligand to the former, to downregulate early inflammatory gene
      expression. However, on LPS rechallenge, AhR engaged in long-term regulation of
      systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1
      (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation
      and signalling ability. The resulting endotoxin-tolerant state was found to
      protect mice against immunopathology in Gram-negative and Gram-positive
      infections, pointing to a role for AhR in contributing to host fitness. 

PMID- 24930770
TI  - C. elegans male mating behavior. Introduction.

PMID- 24930771
TI  - Hox gene regulation and timing in embryogenesis.
AB  - Hox genes are critical regulators of embryonic development in bilaterian animals.
      They exhibit a unique mode of transcriptional regulation where the position of
      the genes along the chromosome corresponds to the time and place of their
      expression during development. The sequential temporal activation of these genes
      in the primitive streak helps determining their subsequent pattern of expression
      along the anterior-posterior axis of the embryo, yet the precise correspondence
      between these two collinear processes is not fully understood. In addition,
      vertebrate Hox genes evolved similar modes of regulation along secondary body
      axes, such as the developing limbs. We review the current understanding of the
      mechanisms operating during activation, maintenance and silencing of Hox gene
      expression in these various contexts, and discuss the evolutionary significance
      of their genomic organization. 

PMID- 24930772
TI  - Redox regulation of ion channels.
AB  - Reactive oxygen species and reactive nitrogen species (ROS/RNS) are often by
      products of biochemical reactions, but are increasingly recognized as important
      second messengers involved in regulation of distinct cellular functions. Mild and
      reversible oxidation of certain amino acids within protein polypeptide chains is
      known to precisely control the function of transcription factors, protein kinases
      and phosphatases, receptors, pumps, ion channels, and so on. Conversely, under
      pathological conditions, high amounts of oxidants irreversibly oxidize DNA,
      lipids, and proteins and have deleterious effects on cells, ultimately causing
      cell death. ROS/RNS can thus be involved in the initiation and progression of
      many pathological conditions. Within this Forum, seven reviews and one original
      article summarize the current knowledge regarding redox regulation of various ion
      channels and ion conducting receptors. These include the recently identified
      mitochondrial Ca2+ uniporter and Orai Ca2+ channels, as well as selected members
      of the families of transient receptor potential, voltage-gated Ca2+, P2X, voltage
      gated K+, and IP3R/RyR channels. In summary, all authors agree on the functional
      importance of redox-ion channel interplay. However, it is also clear that this is
      an emerging field of research where much has to be learned about intra- and
      extracellular sources, concentrations, and types of oxidants. Given their often
      short-lived nature and effective cellular buffering systems, the development of
      tools to measure local ROS production in living cells as well as detailed
      proteomic approaches to pinpoint protein targets and redox modifications are of
      importance.

PMID- 24930769
TI  - Dual Aurora A and JAK2 kinase blockade effectively suppresses malignant
      transformation.
AB  - Aurora A and JAK2 kinases are involved in cell division and tumor cell survival,
      respectively. Here we demonstrate that ectopic expression of Aurora A and JAK2
      together is more effective than each alone at inducing non-transformed cells to
      grow in an anchorage-independent manner and to invade. Furthermore, siRNA
      silencing or pharmacological inhibition of Aurora A and JAK2 with Alisertib and
      Ruxolitinib, respectively, is more effective than blocking each kinase alone at
      suppressing anchorage-dependent and -independent growth and invasion as well as
      at inducing apoptosis. Importantly, we have developed dual Aurora and JAK
      inhibitors, AJI-214 and AJI-100, which potently inhibit Aurora A, Aurora B and
      JAK2 in vitro. In human cancer cells, these dual inhibitors block the auto
      phosphorylation of Aurora A (Thr-288) and the phosphorylation of the Aurora B
      substrate histone H3 (Ser-10) and the JAK2 substrate STAT3 (Tyr-705).
      Furthermore, AJI-214 and AJI-100 inhibit anchorage dependent and independent cell
      growth and invasion and induce G2/M cell cycle accumulation and apoptosis.
      Finally, AJI-100 caused regression of human tumor xenografts in mice. Taken
      together, our genetic and pharmacological studies indicate that targeting Aurora
      A and JAK2 together is a more effective approach than each kinase alone at
      inhibiting malignant transformation and warrant further advanced pre clinical
      investigations of dual Aurora A/JAK2 inhibitors as potential anti tumor agents. 

PMID- 24930773
TI  - Identification of pheromone synergists for Rhynchophorus ferrugineus trapping
      systems from Phoenix canariensis palm volatiles.
AB  - Trapping systems for the red palm weevil, Rhynchophorus ferrugineus Olivier, rely
      on the use of natural plant odor sources to boost the attractiveness of the
      aggregation pheromone. The identification of the key odorants involved in
      attraction is essential in the development of a synthetic pheromone synergist to
      replace the nonstandardized use of plant material in traps. Canary Islands date
      palms (Phoenix canariensis) have become preferred hosts for R. ferrugineus in
      Europe; thus, the volatile profile of different P. canariensis plant materials,
      including healthy and infested tissues, is investigated in the present work by
      means of solid phase microextraction (SPME-GC-MS), aimed to identify pheromone
      synergists. The electroantennography (EAG) response of the compounds identified
      was recorded, as well as the preliminary field response of several EAG-active
      compounds. The so-called "palm esters" (ethyl acetate, ethyl propionate, ethyl
      butyrate, and propyl butyrate) elicit the strongest EAG responses but performed
      poorly in the field. Mixtures of esters and alcohols give evidence of better
      performance, but release rates need further optimization. 

PMID- 24930774
TI  - Ethanol reduces lifespan, body weight, and serum alanine aminotransferase level
      of aldehyde dehydrogenase 2 knockout mouse.
AB  - BACKGROUND: The aldehyde dehydrogenase 2 (Aldh2) knockout mouse is an animal
      model of a polymorphism at the human ALDH2 locus (ALDH2*2). To detect differences
      in the basic phenotype of this animal model, lifespan, body weight (BW), and
      serum alanine aminotransferase (ALT) level were evaluated. METHODS: Aldh2(+/+) ,
      Aldh2(+/-) , and Aldh2(-/-) mice were maintained, from 10 weeks of age, on
      standard solid food, with liquid supplied as ethanol (EtOH) solution at a
      concentration of 0 to 20% (forced EtOH consumption). RESULTS: For animals
      provided with water (without EtOH), mice of the distinct genotypes exhibited no
      difference in lifespan, with the mean values ranging from 90 to 96 weeks for
      female mice and 97 to 105 weeks for male mice. For animals provided with EtOH,
      there was a dose-dependent reduction of lifespan in Aldh2(-/-) mice with p for
      trend <0.001. For example, the mean lifespans of the Aldh2(-/-) females in the 0,
      3, 10, and 20% groups were 95, 85, 70, and 29 weeks, respectively. No influence
      on lifespan was found for Aldh2(+/+) and Aldh2(+/-) mice. BW and ALT level of
      Aldh2(-/-) mice were significantly lower than those of Aldh2(+/+) mice when the
      mice were treated with EtOH. While multiple regression analysis suggested that
      the BW and ALT level in Aldh2(-/-) mice correlated with lifespan, adjustment for
      EtOH concentration revealed that this correlation was not significant (i.e.,
      reflected EtOH dependence). CONCLUSIONS: Aldh2(-/-) mice were unchanged in terms
      of their basic phenotype under standard laboratory conditions. However, chronic
      EtOH administration (forced consumption) in these mice resulted in dose-dependent
      reductions in lifespan, BW, and serum ALT level.

PMID- 24930775
TI  - Surfactant-free CO2-based microemulsion-like systems.
AB  - The presence of water-rich and water-lean nanodomains in a transparent,
      pressurized "water-acetone-CO2" mixture was revealed by Raman spectroscopy. This
      nano-structured liquid can be classified as a surfactant-free microemulsion-like
      system and has the capacity to dissolve hydrophobic compounds, such as ibuprofen,
      in the presence of large amounts of water. This finding opens new opportunities
      in the fields of confined reactions and material templating. 

PMID- 24930776
TI  - Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein
      interaction.
AB  - BACKGROUND AND PURPOSE: The OX40-OX40L protein-protein interaction (PPI) is an
      important cell-surface signalling co-stimulatory regulator within the TNFR
      superfamily (TNFRSF) and a promising therapeutic target for immunomodulation.
      PPIs are difficult to modulate using small-molecules. Here, we describe the
      identification of a small-molecule OX40 modulator and confirm its partial agonist
      character. EXPERIMENTAL APPROACH: Cell-free screening assays were developed and
      used to identify OX40-OX40L inhibitors. Modified versions of this assay were used
      to elucidate the binding partner and the binding nature of active compounds. OX40
      transfected sensor cells with NF-kappaB reporters were constructed and used to
      confirm and characterize activity and specificity. Immunomodulatory activity and
      partial agonist nature were further confirmed by ex vivo T-cell polarization
      assays. KEY RESULTS: Several compounds that concentration-dependently affected
      OX40-OX40L were identified. Cell assays indicated that they were partial agonists
      with low micromolar potency and adequate selectivity. Under polarizing conditions
      based on TGF-beta, the most promising compound mimicked the effect of an
      agonistic anti-OX40 antibody in suppressing regulatory T-cell generation and
      diverting CD4(+) CD62L(+) Foxp3(-) cells to TH 9 phenotype in vitro. CONCLUSIONS
      AND IMPLICATIONS: We identified, to our knowledge, the first small-molecule
      compounds able to interfere with OX40-OX40L binding and, more importantly, to act
      as partial agonists of OX40. This is particularly interesting, as small-molecule
      agonism or activation of PPIs is considered unusually challenging and there are
      only few known examples. These results provide proof-of-principle evidence for
      the feasibility of small-molecule modulation of the OX40-OX40L interaction and
      for the existence of partial agonists for TNFRSF-PPIs.

PMID- 24930778
TI  - Lithium heterocuprates: the influence of the amido group on organoamidocuprate
      structures.
AB  - Lithium organoamidocuprates of the general stoichiometry LiCuR(NR) are an
      important class of organocopper reagents and have found widespread application in
      conjugate addition and other bond-forming reactions. The dependence of the
      structures and equilibrium of these species on the steric and electronic
      properties of the amido group is reported in both the solid state and in
      solution. Three different cuprate complexes have been crystallographically
      characterized: the organoamidocuprate [Cu2Li2Mes2TMP2] (2) (TMP = 2,2,6,6
      tetramethylpiperidide) which is shown to adopt a head-to-tail conformation;
      [Cu2Li2(N(CH2Ph)CH2CH2NMe2)4] (3 ) which is a homoamidocuprate and contains
      additional coordination of the lithium centres from intra-molecular tertiary
      amine groups; and the diastereomeric organoamidocuprate [Cu2Li2Mes2(N(R
      CH(Ph)Me)(CH2CF3))2] (4) which adopts a head-to-head conformation. Complex 4 is
      unique in being the first crystallographically characterised example of a head-to
      head isomer of a heterocuprate, and its structure also has implications for the
      use of scalemic amidocuprates in asymmetrically induced conjugate addition. The
      solution equilibria of all new complexes have also been studied using (7)Li NMR
      spectroscopy, and in each case the species observed in the crystal structure was
      shown to also be the predominant isomer in solution.

PMID- 24930779
TI  - Differences in elements between intact and disrupted human ligamenta capitum
      femorum.
AB  - To compare the element compositions between intact (i.e., intact throughout its
      length) and disrupted (i.e., ligament no longer attached to the attachment)
      ligaments, the contents of elements in the human ligamenta capitum femorum (LCF)
      were analyzed by inductively coupled plasma-atomic emission spectrometry.
      Histological and immunohistological assessments were also performed in both
      groups. The subjects were 8 men and 32 women. Trace element analyses showed that
      the sulfur and iron contents were significantly greater in the intact group than
      in the disrupted group, while the phosphorus and magnesium contents were
      significantly smaller in the intact group than in the disrupted group. The
      calcium and zinc contents were smaller in the intact group than in the disrupted
      group, with no significant differences. Histologically, there were fibrocartilage
      cells and extracellular matrix metachromasia in ligaments of the intact group. In
      contrast, fibrocartilage cells disappeared, and fat cells appeared instead of
      collagen fibrils in ligaments of the disrupted group. The LCFs of the intact
      group were immunohistologically positive for all components examined including
      collagens, glycosaminoglycans, and proteoglycans. The increase in sulfur
      suggested the presence of high glycosaminoglycan levels associated with
      fibrocartilaginous metaplasia in the ligament by compressive force. The reduction
      in iron may show a decreased number of blood vessels in the synovium after
      ligament disruption. The increases in phosphorus, magnesium, and calcium are
      indicative of degenerative changes including calcification and ossification. We
      conclude that differences in the contents of elements between intact and
      disrupted LCFs indicate degenerative alterations to the ligament structure after
      disruption. 

PMID- 24930780
TI  - Selective on site separation and detection of molecules in diluted solutions with
      super-hydrophobic clusters of plasmonic nanoparticles.
AB  - Super-hydrophobic surfaces are bio-inspired interfaces with a superficial texture
      that, in its most common evolution, is formed by a periodic lattice of silicon
      micro-pillars. Similar surfaces reveal superior properties compared to
      conventional flat surfaces, including very low friction coefficients. In this
      work, we modified meso-porous silicon micro-pillars to incorporate networks of
      metal nano-particles into the porous matrix. In doing so, we obtained a
      multifunctional-hierarchical system in which (i) at a larger micrometric scale,
      the super-hydrophobic pillars bring the molecules dissolved in an ultralow
      concentration droplet to the active sites of the device, (ii) at an intermediate
      meso-scale, the meso-porous silicon film adsorbs the low molecular weight content
      of the solution and, (iii) at a smaller nanometric scale, the aggregates of
      silver nano-particles would measure the target molecules with unprecedented
      sensitivity. In the results, we demonstrated how this scheme can be utilized to
      isolate and detect small molecules in a diluted solution in very low abundance
      ranges. The presented platform, coupled to Raman or other spectroscopy
      techniques, is a realistic candidate for the protein expression profiling of
      biological fluids. 

PMID- 24930777
TI  - TLX: A master regulator for neural stem cell maintenance and neurogenesis.
AB  - The orphan nuclear receptor TLX, also known as NR2E1, is an essential regulator
      of neural stem cell (NSC) self-renewal, maintenance, and neurogenesis. In
      vertebrates, TLX is specifically localized to the neurogenic regions of the
      forebrain and retina throughout development and adulthood. TLX regulates the
      expression of genes involved in multiple pathways, such as the cell cycle, DNA
      replication, and cell adhesion. These roles are primarily performed through the
      transcriptional repression or activation of downstream target genes. Emerging
      evidence suggests that the misregulation of TLX might play a role in the onset
      and progression of human neurological disorders making this factor an ideal
      therapeutic target. Here, we review the current understanding of TLX function,
      expression, regulation, and activity significant to NSC maintenance, adult
      neurogenesis, and brain plasticity. This article is part of a Special Issue
      entitled: Nuclear receptors in animal development. 

PMID- 24930781
TI  - The difficult-to-control spread of carbapenemase producers among
      Enterobacteriaceae worldwide.
AB  - The spread of carbapenemase producers in Enterobacteriaceae has now been
      identified worldwide. Three main carbapenemases have been reported; they belong
      to three classes of beta-lactamases, which are KPC, NDM, and OXA-48. The main
      reservoirs of KPC are Klebsiella pneumoniae in the USA, Israel, Greece, and
      Italy, those of NDM are K. pneumoniae and Escherichia coli in the Indian
      subcontinent, and those of OXA-48 are K. pneumoniae and Escherichia coli in North
      Africa and Turkey. KPC producers have been mostly identified among nosocomial
      isolates, whereas NDM and OXA-48 producers are both nosocomial and community
      acquired pathogens. Control of their spread is still possible in hospital
      settings, and relies on the use of rapid diagnostic techniques and the strict
      implemention of hygiene measures. 

PMID- 24930782
TI  - Examining antenatal health literacy in Ghana.
AB  - PURPOSE: To explore Ghanaian pregnant women's understanding and recognition of
      danger signs in pregnancy, birth preparedness and complication readiness, and
      their understanding of newborn care. DESIGN: An exploratory, qualitative study
      design was used. METHODS: Data were gathered through six focus group discussions
      with 68 pregnant women attending antenatal care at a busy urban hospital in
      Ghana. Qualitative and descriptive data were analyzed using SPSS version 21.
      Health literacy was used as the guiding framework to analyze the qualitative
      data. Data were analyzed in the content domains of (a) understanding and
      recognition of danger signs in pregnancy, (b) preparedness for childbirth, (c)
      understanding and recognition of danger signs in the newborn, and (d) appropriate
      and timely referral. FINDINGS: Women in this study identified danger signs of
      pregnancy and in the newborn, but had difficulty interpreting and
      operationalizing information they received during antenatal care visits,
      indicating that health education did not translate to appropriate health
      behaviors. Cultural beliefs in alternative medicine, lack of understanding, and
      prior negative encounters with healthcare professionals may have led to
      underutilization of professional midwives for delivery and health services.
      CONCLUSIONS: Women in this study exhibited low health literacy by incorrectly
      interpreting and operationalizing health education received during antenatal
      care. With limited health literacy, pregnant women cannot fully comprehend the
      scope of services that a health system can provide for them and their families.
      CLINICAL RELEVANCE: Achieving the greatest impact with limited time in antenatal
      care is a challenge. Since antenatal care is widely available to pregnant women
      in Ghana, it is vital to reexamine the way antenatal education is delivered.
      Pregnant women must receive health information that is accurate and easy to
      understand in order to make informed health choices that will improve maternal
      and child health.

PMID- 24930783
TI  - Thymic stromal lymphopoietin: a central regulator of allergic asthma.
AB  - INTRODUCTION: Epithelial cell-derived mediators have emerged as key players for
      instigating local remodeling and the associated cellular inflammation in
      asthmatic airways. In particular, the epithelial-derived cytokine, thymic stromal
      lymphopoietin (TSLP), has been identified as a master switch for allergic
      inflammation. AREAS COVERED: TSLP is expressed by structural and immune cells at
      the site of allergen entry in the airways. Stimuli for release of TSLP include
      common triggers of asthma symptoms, and TSLP levels correlate with disease
      severity. TSLP regulates helper T cell 2 (Th2) humoral immunity through
      upregulating OX40L on dendritic cells (DCs), which drives Th2 lymphocytes;
      however, activation of several other cells by TSLP also supports the development
      of Th2 inflammation. Animal models of asthma demonstrate that increased levels of
      TSLP can induce many of the characteristics of asthma. EXPERT OPINION: The work
      conducted to date supports a critical role of TSLP in the pathogenesis of
      allergic asthma. The first clinical trial to block the downstream effects of
      OX40L has shown reduced levels of circulating IgE and airway eosinophils,
      confirming the importance of TSLP-induced OX40L levels on DCs. Clinical trials
      with TSLP blockade are underway and will unequivocally confirm whether TSLP is
      indeed a key driver of allergic inflammation in asthma.

PMID- 24930786
TI  - Editorial.

PMID- 24930787
TI  - Obsessive-compulsive disorder and spectrum across the life span.
AB  - An obsessive-compulsive disorder (OCD) spectrum has been proposed, which includes
      a group of disorders that share certain features with OCD including clinical
      symptoms (repetitive behaviours and thoughts), neurobiology (e.g.
      neurotransmitters) and preferential response to anti-obsessional treatments, such
      as the selective serotonin reuptake inhibitors (SSRIs). Three distinct clusters
      have been identified within the OCD spectrum, i.e. disorders concerning
      preoccupations with bodily sensations or appearance, impulsive disorders, and
      neurologically based disorders, and these share phenotypic features. Using one
      example from each of these clusters, body dysmorphic disorder (BDD), pathological
      gambling (PG) and autism, respectively, the phenomenology, neurobiology and
      pharmacotherapy indicates that specific biological factors are shared by OCD and
      by these disorders and correlate with the severity of repetitive behaviours.
      Thus, in common with OCDs, in BDD there is increased activity in the limbic
      regions; in PG there is evidence of deficiencies in 5-HT function and receptors;
      and in autism there are restricted interests and repetitive behaviours which may
      be influenced by serotonergic mechanisms. Our findings support the notion that
      targeted treatments, for example using SSRIs, for the behaviours associated with
      these disorders are effective. Our review considers one SSRI treatment in
      particular, fluvoxamine, and conclusions should be drawn in light of this.
      Further testing of our hypothesis would be prudent to confirm its validity. 

PMID- 24930785
TI  - Immune reconstitution-associated cutaneous sarcoid-like eruption in a patient
      with previous disseminated cutaneous leishmaniasis: a diagnostic challenge.

PMID- 24930788
TI  - Mirtazapine versus paroxetine in panic disorder: an open study.
AB  - Introduction Open studies suggest that mirtazapine has efficacy in panic disorder
      treatment. We designed an open study that evaluates changes induced by
      mirtazapine compared with paroxetine in panic disorder. Methodology Patients 18
      65 years old consecutively referred to a psychiatry liaison service with panic
      disorder (DSM-IV criteria) were offered either mirtazapine or paroxetine
      treatment. Results There were statistically significant reductions from baseline
      to week 3 and from week 3 to 8 for mirtazapine and paroxetine groups for: number
      of panic attacks, Beck Anxiety or Depression Inventory (BAI, BDI) Clinical Global
      Impresion (CGI) of panic disorder severity and CGI of panic disorder response
      (these variables were evaluated by the patient, the clinician or a blind
      evaluator). Responders at week 3 (BAI decrease of 50%) were 83% for the
      mirtazapine group and 84% for the paroxetine group. Responders at week 8 (number
      of panic attacks equal to 0) were 77% for the mirtazapine group and 73% for the
      paroxetine group Statistically significant differences between mirtazapine and
      paroxetine were found for number of panic attacks at weeks 3 and 8 and BAI at
      week 3, suggesting a faster response for mirtazapine. Responders at week 8
      maintained a no recurrence figure of 95% at follow-up 6 months later. Panic
      disorder either with or without comorbid depression improved in both groups of
      treatment. Discussion Our study supports the hypothesis that mirtazapine has
      efficacy in the treatment of panic disorder either with or without comorbid
      depression. 

PMID- 24930789
TI  - Correlates of subjective well-being in schizophrenic patients treated with
      atypical antipsychotics.
AB  - Objective A growing body of research indicates that a low subjective well-being
      (SW) may be predictive of non-adherence and less favourable outcome. This study
      examined baseline variables and variables in the course of treatment hypothesised
      to be associated with later SW. Methods Sixty-three inpatients with
      schizophreniform disorder or schizophrenia were randomly assigned to treatment
      with various atypical antipsychotics after a wash-out phase of 2 days. Subjects
      were evaluated with a protocol that examined psychopathology (Positive and
      Negative Symptom Scale, PANSS), side effects (Scandinavian Society of
      Pharmacology, UKU), and subjective well-being (Subjective Well-being under
      Neuroleptic treatment, SWN) at baseline and endpoint (mean duration of treatment
      39.9 days). Two-thirds of subjects were multiple episode schizophrenic inpatients
      pre-treated with antipsychotics. Results Multiple regression analyses revealed
      that the PANSS negative score, neurological side effects, and SWN at baseline, as
      well as change of the PANSS positive score between baseline and endpoint, were
      associated independently with SW at endpoint (R(2)=0.55 after exclusion of two
      subjects). Conclusions Patients with low SW, severe negative symptoms, and
      neurological side effects, all at baseline, as well as those without improvement
      or deterioration of positive symptoms are at risk of low SW later in treatment
      and, most likely, of non-adherence. 

PMID- 24930790
TI  - Prognosis of postpartum psychiatric disorders in a Turkish sample.
AB  - Objective The postpartum period represents a time of increased risk for
      psychiatric disorders. Postpartum depression is especially very common. Many
      aetiological risk factors have been reported for postpartum psychiatric
      disorders. The purpose of this study was to evaluate the postpartum psychiatric
      disorders in a Turkish sample and discuss their course. Methods The files of 6000
      inpatients who were admitted to Gazi University School of Medicine Psychiatry
      Department were evaluated retrospectively, and 67 patients were chosen whose
      psychiatric illness had began puerperally. These patients were grouped according
      to age of onset of the illness, number of episodes and the type of these
      episodes, their postpartum psychiatric diagnoses and illness prognosis. Results
      Of 6000 patients, 67 (1.11%) were diagnosed as having a postpartum psychiatric
      disorder: 56.7% (n=38) were diagnosed as having a postpartum psychotic disorder,
      while 35.8% (n=24) as having an affective disorder. Forty-seven patients (70.1%)
      received a diagnosis of major psychiatric disorder during their follow-up.
      Conclusion These results show that postpartum diagnoses may show a chronic course
      and cause a life-time psychiatric illness and therefore patients should be
      monitored carefully for psychotic symptoms even after the acute period is over. 

PMID- 24930791
TI  - Suicide and undetermined death by drowning.
AB  - Background Incidence of drowning varies among countries and even communities
      within the same country. The manner of death may remain undetermined even when
      the diagnosis of drowning is confirmed or excluded. It is expected that drowning
      suicide rates in some of the available studies may have been over- or under
      reported because of misclassification. Objectives This study presents data on the
      time trends, age/sex mortality rates from death by drowning in England and Wales
      between 1979 and 2001. All coroners' verdicts in death by drowning; suicide,
      deaths undetermined whether accidentally or purposely inflicted were examined.
      Methods Counts of suicide due to drowning and submersion (ICD 9 codes; E954) and
      undetermined injury deaths (E984) 1 , reported in England and Wales between 1979
      and 2001 were obtained from National Statistics (ONS). National population
      estimates were used to calculate age-specific rates and age-standardised rates of
      death by drowning. Results Over the last 23 years, there has been a gradual and
      significant reduction in drowning deaths. The decline in drowning suicide was
      less evident in the elderly, particularly those over the age of 75. During the
      study period, 62 and 38% of all death by drowning attracted an open verdict and
      suicide, respectively. Elderly drowning appear to attract more verdicts of
      suicide compared to younger age groups (odds ratio 4.3, 95% CI 2.3-8.3). Women,
      particularly elderly, are more likely to have a suicide verdict returned in
      drowning compared to men (odds ratio 1.5, 95% CI 1.1-1.6). Conclusion The high
      rate of open verdicts in death by drowning over the study period and compared to
      any other method of fatal self harm in England and Wales confirms the
      difficulties in reaching a firm conclusion in drowning death. Combining suicide
      and all undetermined deaths in drowning in nationally collected statistics may
      result in grossly exaggerated rates and misleading trends in suicidal drowning. 

PMID- 24930792
TI  - Urinary incontinence in schizophrenic patients treated with atypical
      antipsychotics: urodynamic findings and therapeutic perspectives.
AB  - Objective The present study was a urodynamic evaluation of schizophrenic patients
      with urinary incontinence occurring during treatment with atypical antipsychotics
      Methods A total of 12 schizophrenic patients (mean age = 30.7 years, SD = 6.5)
      presenting urinary incontinence during treatment with atypical antipsychotics at
      stable doses underwent urodynamic evaluations. Clinical assessment included the
      administration of Positive and Negative Syndrome Scale (PANSS) Results Four
      patients out of 12 presented urodynamic patterns consistent with an overactive
      bladder, while five patients presented reduced bladder compliance; only three
      patients showed normal urodynamic patterns Conclusion Detrusor overactivity is a
      condition associated with urinary incontinence in schizophrenic patients treated
      with atypical antipsychotics. Urodynamic evaluations can improve our knowledge of
      the mechanisms that subtend atypical antipsychotic-induced incontinence, an
      invalidating side-effect with strong repercussion on compliance and
      rehabilitation in schizophrenic patients. 

PMID- 24930793
TI  - Assessment of sexual drive and desire in women with premenstrual dysphoric
      disorder who have been treated with fluoxetine.
AB  - Objective To explore the impact of treatment with fluoxetine on sexual drive and
      desire (SDD) in women with premenstrual dysphoric disorder (PMDD). Methods Data
      were collected during a randomised, controlled, double-blind trial evaluating the
      efficacy of fluoxetine 20 or 60 mg/day versus placebo in the treatment of women
      with PMDD. Study subjects rated their SDD on the Premenstrual Tension Scale, Self
      Rating (PMTS-SR) during their follicular and luteal phases of the placebo run in
      cycles and the double-blind treatment cycles. Data were analyzed using chi-square
      test. Results Data were available for 184 subjects who rated their SDD during the
      follicular and luteal phases of two baseline (placebo) cycles and the following
      two treatment cycles. There was a trend for more women on fluoxetine to report
      improvement in luteal phase SDD compared to women on placebo (P=0.057).
      Conclusions Our data, contrary to expectations, suggest that fluoxetine treatment
      may restore SDD in women who experience decreased SDD as part of a cluster of
      symptoms associated with PMDD. Future trials with SSRIs should include specific
      measures of sexual functioning to further examine the potential beneficial versus
      side effects of these medications as they relate to phases of the menstrual
      cycle. 

PMID- 24930794
TI  - A prescription survey of antipsychotic use in England and Wales following the
      introduction of NICE guidance.
AB  - Objective : In the United Kingdom (UK) the National Institute for Clinical
      Excellence (NICE) has recommended the use of atypical antipsychotics for the
      treatment of schizophrenia. As part of its guidance it discourages the concurrent
      use of typical and atypical antipsychotics. In previous prescribing surveys
      antipsychotic polypharmacy has been noted to be widespread. We sought to evaluate
      atypical antipsychotic prescribing after the publication of NICE guidance. Method
      : We invited psychiatric centres in England and Wales to participate, in March
      2004, in an atypical antipsychotic prescribing survey of hospital in-patients.
      Results : Thirty-six in-patient units submitted data for 2012 patients. After
      exclusions, 1092 patients were eligible. Of these, 28.6% (312) were prescribed a
      typical alongside an atypical antipsychotic and 19.3% (211) were prescribed high
      dose antipsychotics. Co-prescription was more prevalent in patients aged 40 years
      and above (32.0 vs. 25.3%; P=0.018). It was also noted that in centres employing
      senior pharmacists, co-prescription was more common (28.6 vs. 14.3%; P=0.03).
      High-dose treatment was more commonly observed in patients of a white ethnic
      background (20.6 vs. 13.9%; P=0.02) as well as in patients aged 40 years and
      above (24.4 vs. 15.0%; P<0.001). Prescription of anticholinergics was
      significantly more prevalent in those receiving atypical and typical combinations
      than atypicals alone (26.0 vs. 12.0%; P<0.001). Conclusions : Antipsychotic
      polypharmacy remains commonplace. Similarly the prescription of high-dose
      antipsychotics is also widespread. 

PMID- 24930795
TI  - Belgian consensus on metabolic problems associated with atypical antipsychotics.
AB  - A workshop was convened by a panel of psychiatrists, diabetologists and
      pharmacists from major Belgian hospitals to review the latest information
      relating to the risks with second-generation antipsychotics (SGA) for the
      development of metabolic disorders, especially impaired glucose tolerance,
      diabetes mellitus and dyslipidemia. The panelists sought to formulate
      recommendations for practising psychiatrists when initiating and maintaining
      therapy with SGA, and for the switch of SGA or initiation of further treatment if
      metabolic complications occur. In addition, recommendations for counselling of
      the patient and for the cooperation between the psychiatrist and the general
      physician or diabetologist, respectively, were provided. 

PMID- 24930796
TI  - Panic disorder due to ingestion of single dose ecstasy.
AB  - Ecstasy or MDMA (3,4 methylenedioxymethamphetamine) is a popularly consumed
      substance worldwide. There have been various reports documented in the literature
      that have attributed MDMA to precipitating the onset of a wide range of
      persistent psychiatric symptoms. Additionally, there is increasing evidence of a
      permanent injury to the serotonergic neurons. In this case report, a person
      demonstrating panic disorder after the ingestion of a single dose of MDMA is
      described and potential mechanisms of action are reviewed. 

PMID- 24930797
TI  - Acute psychological stress-induced water intoxication.
AB  - Excessive water drinking is a recognised feature of schizophrenia. We present
      here a case of excessive water drinking precipitated by acute psychological
      stress. A 52-year-old woman, with no previous mental health problems, was found
      in a state of altered consciousness and was profoundly hyponatraemic. She had
      consumed excess amount of water due to severe mental stress. She was treated with
      hypertonic saline followed by fluid restrictions. The water intoxication had
      caused brain damage which led to behavioural changes and impaired cognition. We
      describe the pathophysiology of water intoxication. 

PMID- 24930798
TI  - Cigarette smoking and psychiatric disorders in Hungary.
AB  - Data from the United States and from several European countries show that
      patients with major mood disorders, schizophrenia and social phobia smoke at
      significantly higher rates than the general population. However, there are no
      published results on this field from Central Europe, including Hungary. In the
      present study, the rate of current and lifetime smoking of the consecutively
      screened outpatients with DSM-IV unipolar major depression (n=92), bipolar
      disorder (n=60), schizophrenia (n=80), schizoaffective disorder (n=42) and panic
      disorder without major depression (n=60) were assessed and the data were compared
      to the controls (n=5503), representative for the general population of Hungary.
      The results showed that, compared to controls, the rates of current and lifetime
      smoking were significantly higher among patients with unipolar major depression,
      bipolar disorder, schizophrenia and schizoaffective disorder, but not among
      patients with panic disorder without major depression. The findings support
      previous findings from other countries on the strong relationship between
      cigarette smoking and major mood and schizophrenic spectrum disorders. 

PMID- 24930799
TI  - Strong mixed-handedness in schizophrenia.
AB  - There is still considerable discussion of whether schizophrenia is a lateralized
      brain disorder. In fact, schizophrenic patients appear to exhibit a shift away
      from dexterity, as confirmed by the majority of the 23 publications dealing with
      this question (14 positive, seven null, two paradoxical). However, quite a few of
      these positive studies have distinguished between left-handedness and mixed
      handedness (MH), thus lacking specificity. Whereas prior studies failed to
      specify schizophrenic MH, we could observe a significant relationship between
      strong MH and schizophrenia in male patients in a relatively small group due to
      sex differentiation and accurate application of Annett's hand preference
      questionnaire. 

PMID- 24930800
TI  - Outcome and risk of revision following shoulder replacement in patients with
      glenohumeral osteoarthritis.
AB  - This thesis includes four studies focusing on the functional outcome, shoulder
      specific quality of life and risk of revision following shoulder replacement in
      patients with glenohumeral osteoarthritis without symptomatic rotator cuff
      pathology. The Danish version of WOOS, translated according to international
      standardized guidelines, had substantial psychometric properties comparable to
      the original version. It is recommendable to use WOOS in the evaluation of
      patients with glenohumeral osteoarthritis treated with shoulder replacement. Data
      from DSR showed that the shoulder specific quality of life following total
      shoulder arthroplasty was superior to that of hemiarthroplasty (resurfacing
      hemiarthroplasty and stemmed hemiarthroplasty). The difference between stemmed
      hemiarthroplasty and resurfacing hemiarthroplasty was small and did not exceed
      the minimal clinically important difference. The revision rate following
      resurfacing hemiarthroplasty was surprisingly high compared with previous reports
      but there were no statistical significant differences in revision rate between
      arthroplasty designs. The shoulder specific quality of life and revision rate in
      patients under the age of 55 was worrying. The use of resurfacing
      hemiarthroplasty has relied on the results from case series only. The efficacy in
      the treatment of glenohumeral osteoarthritis has been promising but the CMS found
      in the randomized clinical trial indicate that the functional outcome may be
      inferior to that of stemmed hemiarthroplasty and less favourable than previously
      reported. However, the limited number of patients may have influenced the results
      and a larger definitive RCT is needed.Shoulder replacement is relevant and
      effective in the treatment of glenohumeral osteoarthritis; however, resurfacing
      hemiarthroplasty was associated with a poorer outcome and a higher risk of
      revision than previously assumed especially in patients under the age of 55.
      Based on data from this thesis, and based on existing knowledge, it seems like
      total shoulder arthroplasty should be preferred in the treatment of glenohumeral
      osteoarthritis. Shoulder replacement is rarely indicated in younger patients
      where other treatment options (e.g., physiotherapy; intraarticular injections of
      hyaluronate; and joint preserving surgery) should be considered until the
      efficacy of shoulder replacement has been more thoroughly documented.

PMID- 24930801
TI  - Effect of maternal separation and chronic stress on hippocampal-dependent memory
      in young adult rats: evidence for the match-mismatch hypothesis.
AB  - Adverse experiences early in life may sensitize the hippocampus to subsequent
      stressors throughout the individual's life. We analyzed in male rats, whether,
      the interaction between early maternal separation and chronic stress affects: (1)
      the volume of the dorsal hippocampus, (2) CA1, CA2/3 and dentate gyrus (DG) and
      (3) hippocampal-dependent memory in adulthood. Male Wistar rats were subjected to
      daily maternal separation for 4.5 h between postnatal days 1-21. From postnatal
      day 50, animals were exposed to a chronic unpredictable stress paradigm during 24
      days. The volumes of the dorsal hippocampus, their areas or strata did not reveal
      significant differences between treatments. Non-maternally separated and stressed
      animals showed poor hippocampal performance in a contextual fear conditioning
      test, with a significant reduction in freezing behavior during post-conditioning
      compared with control and maternally separated and stressed animals. Also, memory
      retrieval 24 h after conditioning was significantly weaker in this group than in
      control animals. Memory performance in maternally separated and stressed rats was
      similar to control animals. Our results show an interaction between early
      environment experiences and chronic variable stress in young adulthood as
      evidence that early stressful experiences do not necessarily lead to a negative
      outcome but can help in maintaining brain plasticity and increase fitness when
      animals reach adulthood.

PMID- 24930802
TI  - Does the arrival index predict physiological stress reactivity in children.
AB  - Knowledge about children's stress reactivity and its correlates is mostly based
      on one stress task, making it hard to assess the generalizability of the results.
      The development of an additional stress paradigm for children, that also limits
      stress exposure and test time, could greatly advance this field of research.
      Research in adults may provide a starting point for the development of such an
      additional stress paradigm, as changes in salivary cortisol and alpha-amylase
      (sAA) over a 1-h pre-stress period in the laboratory correlated strongly with
      subsequent reactivity to stress task (Balodis et al., 2010,
      Psychoneuroendocrinology 35:1363-73). The present study examined whether such
      strong correlations could be replicated in 9- to 11-year-old children. Cortisol
      and sAA samples were collected from 158 children (83 girls) during a 2.5-h visit
      to the laboratory. This visit included a 1-h pre-stress period in which children
      performed some non-stressful tasks and relaxed before taking part in a
      psychosocial stress task (TSST-C). A higher cortisol arrival index was
      significantly and weakly correlated with a higher AUCg but unrelated to cortisol
      reactivity to the stressor. A higher sAA arrival index was significantly and
      moderately related to lower stress reactivity and to a lower AUCi. Children's
      personality and emotion regulation variables were unrelated to the cortisol and
      sAA arrival indices. The results of this study do not provide a basis for the
      development of an additional stress paradigm for children. Further replications
      in children and adults are needed to clarify the potential meaning of an arrival
      index.

PMID- 24930804
TI  - The use of venous jump grafts in pancreatic transplantation - no difference in
      patient or allograft outcomes - an update of the UNOS database.
AB  - Venous jump grafts are used in pancreas transplantation to salvage a pancreas
      with a short portal vein or to facilitate an easier anastomosis. There have been
      no large studies evaluating the safety of venous jump grafts in pancreas
      transplantation. We analyzed the UNOS database to determine whether venous jump
      grafts are associated with graft loss or patient death. Data from UNOS on all
      adult pancreas transplant recipients 1996-2012 were analyzed. Venous extension
      grafts were used in 2657 cases; they were not in 18 124. Kaplan-Meier/product
      limit estimates analysis demonstrated similar patient survival (p < 0.641) and
      death-censored graft survival (p < 0.351) at one, three, five,10, and 15 yr
      between subjects with and without venous jump grafts. There was a statistically
      significant difference in one-yr unadjusted patient survival between the venous
      extension graft (94.9%) and the no-venous extension graft (95.8%) groups (p <
      0.045) and a borderline difference in one-yr graft survival between the venous
      extension graft (84.1%) and the no-venous extension graft (82.6%) groups (p <
      0.055). There was no significant difference in patient survival or allograft
      survival at the three-, five-, 10-, and 15-yr intervals. The use of venous jump
      grafts is not associated with increased graft loss or mortality.

PMID- 24930803
TI  - Estimating the returns to UK publicly funded cancer-related research in terms of
      the net value of improved health outcomes.
AB  - BACKGROUND: Building on an approach developed to assess the economic returns to
      cardiovascular research, we estimated the economic returns from UK public and
      charitable funded cancer-related research that arise from the net value of the
      improved health outcomes. METHODS: To assess these economic returns from cancer
      related research in the UK we estimated: 1) public and charitable expenditure on
      cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit
      (NMB), that is, the health benefit measured in quality adjusted life years
      (QALYs) valued in monetary terms (using a base-case value of a QALY of GBL25,000)
      minus the cost of delivering that benefit, for a prioritised list of
      interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK
      research; 4) the elapsed time between research funding and health gain; and 5)
      the internal rate of return (IRR) from cancer-related research investments on
      health benefits. We analysed the uncertainties in the IRR estimate using
      sensitivity analyses to illustrate the effect of some key parameters. RESULTS: In
      2011/12 prices, total expenditure on cancer-related research from 1970 to 2009
      was L15 billion. The NMB of the 5.9 million QALYs gained from the prioritised
      interventions from 1991 to 2010 was L124 billion. Calculation of the IRR
      incorporated an estimated elapsed time of 15 years. We related 17% of the annual
      NMB estimated to be attributable to UK research (for each of the 20 years 1991 to
      2010) to 20 years of research investment 15 years earlier (that is, for 1976 to
      1995). This produced a best-estimate IRR of 10%, compared with 9% previously
      estimated for cardiovascular disease research. The sensitivity analysis
      demonstrated the importance of smoking reduction as a major source of improved
      cancer-related health outcomes. CONCLUSIONS: We have demonstrated a substantive
      IRR from net health gain to public and charitable funding of cancer-related
      research in the UK, and further validated the approach that we originally used in
      assessing the returns from cardiovascular research. In doing so, we have
      highlighted a number of weaknesses and key assumptions that need strengthening in
      further investigations. Nevertheless, these cautious estimates demonstrate that
      the returns from past cancer research have been substantial, and justify the
      investments made during the period 1976 to 1995.

PMID- 24930805
TI  - Treatment of central sensitization in patients with 'unexplained' chronic pain:
      an update.
AB  - INTRODUCTION: Central sensitization (CS) is present in a variety of chronic pain
      disorders, including whiplash, temporomandibular disorders, low back pain,
      osteoarthritis, fibromyalgia, headache, lateral epicondylalgia among others. In
      spite of our increased understanding of the mechanisms involved in CS pain, its
      treatment remains a challenging issue. AREAS COVERED: An overview of the
      treatment options we have for desensitising the CNS in patients with CS pain is
      provided. These include strategies for eliminating peripheral sources of
      nociception, as well as pharmacotherapy and conservative interventions that
      primarily address top-down (i.e., brain-orchestrated) mechanisms. EXPERT OPINION:
      A combination of different strategies, each targeting a different 'desensitizing'
      mechanism, might prove superior over monotherapies. Such combined therapy may
      include both bottom-up and top-down (e.g., opioids, combined MU-opioid receptor
      agonist and noradrenaline reuptake inhibitor drugs) strategies. Topically applied
      analgesic therapies have strong potential for (temporally) decreasing peripheral
      nociceptive input (bottom-up approach). Targeting metabolic (e.g., ketogenic
      diets) and neurotrophic factors (e.g., decreasing brain-derived neurotrophic
      factor) are promising new avenues for diminishing hyperexcitability of the CNS in
      central sensitization pain patients. Addressing conservative treatments, pain
      neuroscience education, cognitive behavioural therapy and exercise therapy are
      promising treatments for CS pain.

PMID- 24930806
TI  - Gender differences in biometry prediction error and intra-ocular lens power
      calculation formula.
AB  - PURPOSE: To analyze changes over time in biometry prediction error (BPE) after
      cataract surgery with special reference to the impact of gender and the intra
      ocular lens (IOL) calculation formula. METHODS: About 65% of Swedish cataract
      surgery units participating in the outcome registration of the National Cataract
      Register (NCR) were included in this prospective register study. Data for planned
      and postoperative refraction and keratometry during the month of March 2004-2013
      were analyzed, divided by gender. The newly introduced variables axial length and
      IOL calculation formula were analyzed for March 2013. Gender differences in BPE
      with correct sign (BPESign ) and absolute biometry prediction error (BPEAbs )
      were compared for the Haigis' and Sanders-Retzlaff-Kraff T (SRK/T) formulas.
      RESULTS: The BPEAbs decreased throughout the study period. In 2004-2006, the
      BPEAbs was larger in women than in men (p < 0.05), but this difference
      disappeared from 2007. For 2004 through 2009, the mean BPESign was -0.105 +/-
      0.79D for women, but -0.003 +/- 0.73D for men. After 2009, this myopic error for
      women gradually diminished. The Haigis' formula performed better in women than
      the SRK/T formula (p < 0.001); the SRK/T formula rendered a BPESign similar to
      that from 2004 to 2009 in women. Women had steeper corneas and shorter axial
      lengths than men (p < 0.001). CONCLUSION: The myopic BPE in women - associated
      with steeper corneas and shorter axial lengths - is decreasing, possibly owing to
      an increased use of the Haigis' formula. Using the Haigis' formula to a higher
      extent can potentially further reduce the BPEs after cataract surgery.

PMID- 24930807
TI  - 'Measurement for improvement not judgement' -- the case of percutaneous
      nephrolithotomy.

PMID- 24930808
TI  - Primary herpes simplex infection with genital and extra-genital lesions mimicking
      disseminated gonococcal disease.

PMID- 24930809
TI  - Neurosensory assessment in patients with total reconstruction of the
      temporomandibular joint.
AB  - Somatosensory sensitivity and postoperative endogenous pain modulation have not
      been investigated in temporomandibular joint (TMJ) prosthesis patients. The
      objectives of this study were to assess somatosensory function at the TMJ and
      examine possible differences in conditioned pain modulation (CPM) between
      patients with total TMJ prostheses (n=7) and a reference group of healthy
      controls (n=20). Somatosensory abnormalities were assessed using quantitative
      sensory testing (QST), which encompasses thermal and mechanical testing
      procedures. CPM was tested by comparing pressure pain thresholds (PPT) before
      (baseline), during, and after the application of painful and non-painful cold
      stimuli. PPTs were measured at the TMJ and thenar eminence (control). The effect
      of CPM on PPT values was tested with analysis of variance. Three patients
      exhibited mixed somatosensory loss (i.e., decreased thermal and mechanical
      detection) with mixed hyperalgesia (i.e., increased sensitivity to thermal and
      mechanical pain) and two patients exhibited mixed loss with only mechanical
      hyperalgesia. There was a significant decrease in pressure pain sensitivity at
      both sites during painful cold application in healthy controls (P<0.001) but not
      in patients (P=0.476). In conclusion, QST measures demonstrated somatosensory
      abnormalities in patients with total TMJ prostheses. Noxious conditioning cold
      stimuli evoked CPM-like effects in healthy subjects but not in patients with TMJ
      reconstruction. 

PMID- 24930810
TI  - Weighted hurdle regression method for joint modeling of cardiovascular events
      likelihood and rate in the US dialysis population.
AB  - We propose a new weighted hurdle regression method for modeling count data, with
      particular interest in modeling cardiovascular events in patients on dialysis.
      Cardiovascular disease remains one of the leading causes of hospitalization and
      death in this population. Our aim is to jointly model the
      relationship/association between covariates and (i) the probability of
      cardiovascular events, a binary process, and (ii) the rate of events once the
      realization is positive-when the 'hurdle' is crossed-using a zero-truncated
      Poisson distribution. When the observation period or follow-up time, from the
      start of dialysis, varies among individuals, the estimated probability of
      positive cardiovascular events during the study period will be biased.
      Furthermore, when the model contains covariates, then the estimated relationship
      between the covariates and the probability of cardiovascular events will also be
      biased. These challenges are addressed with the proposed weighted hurdle
      regression method. Estimation for the weighted hurdle regression model is a
      weighted likelihood approach, where standard maximum likelihood estimation can be
      utilized. The method is illustrated with data from the United States Renal Data
      System. Simulation studies show the ability of proposed method to successfully
      adjust for differential follow-up times and incorporate the effects of covariates
      in the weighting.

PMID- 24930811
TI  - Assessing the needs of informal caregivers to cancer survivors: a review of the
      instruments.
AB  - OBJECTIVE: Cancer may impact negatively on an informal caregiver's health long
      after treatment has ended. This review identifies the self-report measures
      currently in use to measure caregivers need for support and determines their
      scientific soundness and clinical utility. METHOD: A systematic electronic
      database search of Medline, CINAHL, PsychINFO, BNI ProQuest was conducted. The
      psychometric properties and clinical utility of needs assessment tools for
      caregivers of cancer survivors (excluding advanced disease) were extracted and
      summarised. RESULTS: Seven cancer survivor caregiver needs assessment tools were
      identified. Data on instrument development was well reported, although
      variability was noted in their structure and content. The majority demonstrated
      some degree of reliability and validity; only two were evaluated for test-retest
      reliability (CaSPUN and SPUNS) with only the SPUNS showing a high degree of
      reliability over time. The Health Care Needs Survey (HCNS), Needs Assessment of
      Family Caregivers-Cancer (NAFC-C) and Cancer Caregiving Tasks Consequences and
      Needs Questionnaire (CaTCoN) have been validated at various stages of the cancer
      continuum. Minimal data was available on responsiveness. CONCLUSION: All
      assessment tools identified require further psychometric analysis. For research
      purposes, the use of the SPUNS (with its acceptable test-retest reliability)
      appears most appropriate; although its length may be of concern for clinical use;
      therefore, the shorter SCNS-P&C is likely to be more suitable for use clinically.
      At present, the NAFC-C demonstrates a great potential in both the research and
      clinical environments; however, it requires further psychometric testing before
      it can be fully recommended. Further analysis is necessary on ideal response
      formats and the meaning of a total needs score.

PMID- 24930812
TI  - Implication of mGlu5 receptor in the enhancement of morphine-induced
      hyperlocomotion under chronic treatment with zolpidem.
AB  - Long-term exposure to zolpidem induces drug dependence, and it is well known that
      the balance between the GABAergic and glutamatergic systems plays a critical role
      in maintaining the neuronal network. In the present study, we investigated the
      interaction between GABAA receptor alpha1 subunit and mGlu5 receptor in the
      limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days.
      mGlu5 receptor protein levels were significantly increased after treatment with
      zolpidem for 7 days, and this change was accompanied by the up-regulation of
      phospholipase Cbeta1 and calcium/calmodulin-dependent protein kinase IIalpha,
      which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that
      mGlu5 receptor is directly involved in dopamine-related behavior in mice
      following chronic treatment with zolpidem, we measured morphine-induced
      hyperlocomotion after chronic treatment with zolpidem in the presence or absence
      of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem
      significantly enhanced morphine-induced hyperlocomotion, this enhancement of
      morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5
      receptor antagonist MPEP. These results suggest that chronic treatment with
      zolpidem caused neural plasticity in response to activation of the mesolimbic
      dopaminergic system accompanied by an increase in mGlu5 receptor. 

PMID- 24930813
TI  - Protocatechualdehyde prevents methylglyoxal-induced mitochondrial dysfunction and
      AGEs-RAGE axis activation in human lens epithelial cells.
AB  - Methylglyoxal (MGO), a glucose derived dicarbonyl intermediate, is a major
      precursor of advanced glycation end products (AGEs) which have been linked to the
      development of diabetic cataract. Protocatechualdehyde (PCA), a phenolic acid
      compound, is found in the roots of Salvia miltiorrhiza. This study was to
      investigate the effect of PCA against MGO-induced cytotoxicity in human lens
      epithelial cells (SRA01/04 cells) and the possible involved molecular mechanism.
      The results showed that PCA alleviated MGO-induced mitochondrial dysfunction and
      apoptosis in SRA01/04 cells. Furthermore, PCA was capable of inhibiting MGO
      mediated AGEs formation and blocking receptor of AGEs expression in SRA01/04
      cells. It is concluded that PCA could be useful in attenuation of MGO-induced
      cell damage and the possible mechanism is involved in modulating AGEs-receptor of
      AGEs axis in human lens epithelial cells, which suggests that PCA has a potential
      protective effect on diabetic cataract. 

PMID- 24930814
TI  - Does radiation dose to the vestibule predict change in balance function and
      patient perceived dizziness following stereotactic radiotherapy for vestibular
      schwannoma?
AB  - OBJECTIVE: To date, the majority of the vestibular schwannoma (VS) literature has
      focused on tumor control rates, facial nerve function and hearing preservation.
      Other factors that have been shown to significantly affect quality-of-life (QOL),
      such as dizziness, remain understudied. The primary objective of the current
      study is to investigate the association between radiation dose to the vestibule
      and post-treatment changes in vestibular function and patient reported dizziness
      handicap. MATERIALS AND METHODS: This is a prospective observational pilot study
      at a tertiary academic referral center including all subjects that underwent
      linear accelerator-based stereotactic radiotherapy (SRS) for sporadic VS and
      completed pre-treatment and post-treatment vestibular testing and Dizziness
      Handicap Inventory (DHI) questionnaires. Associations between objective
      vestibular test results, patient-reported DHI scores and radiation dose
      parameters were investigated. RESULTS: Ten patients met inclusion criteria. Tumor
      control was achieved in all individuals. There were no statistically significant
      associations or identifiable trends between radiation dose and change in
      vestibular function or DHI scores. Notably, the four ears receiving the highest
      vestibular dose had minimal changes in vestibular function tests and DHI scores.
      CONCLUSIONS: To the best of our knowledge, no previous reports have described the
      association between radiation dose to the vestibule and post-treatment changes in
      vestibular function and patient reported DHI. Based on these preliminary data,
      radiation dose to the vestibule does not reliably predict change in objective or
      subjective vestibular outcome measures.

PMID- 24930816
TI  - Preparation and mechanism insight of nuclear envelope-like polymer vesicles for
      facile loading of biomacromolecules and enhanced biocatalytic activity.
AB  - The facile loading of sensitive and fragile biomacromolecules, such as glucose
      oxidase, hemoglobin, and ribonucleic acid (RNA), via synthetic vehicles directly
      in pure aqueous media is an important technical challenge. Inspired by the
      nucleus pore complex that connects the cell nucleus and the cytoplasm across the
      nuclear envelope, here we describe the development of a kind of polymeric nuclear
      envelope-like vesicle (NEV) to address this problem. The NEV is tailored to form
      the polymer pore complex (70 nm, similar to a nucleus pore complex) within the
      vesicle membrane based on nanophase segregation, which is confirmed via
      fluorescence spectrometry and dynamic light scattering (DLS) during self
      assembly. This pH-triggered polymer pore complex can mediate the transportation
      of biomacromolecules across the vesicle membrane. Moreover, the NEVs facilitate
      the natural consecutive enzyme-catalyzed reactions via the H(+) sponge effect.
      This simple strategy might also be extended for mimicking other synthetic cell
      organelles.

PMID- 24930815
TI  - Extraction of functional ingredients from spinach (Spinacia oleracea L.) using
      liquid solvent and supercritical CO2 extraction.
AB  - BACKGROUND: In this work three different techniques were applied to extract dry
      leaves of spinach (Spinacia oleracea): solid-liquid extraction (SLE), pressurised
      liquid extraction (PLE) and supercritical fluid extraction (SFE) to investigate
      the influence of extraction solvent and technique on extracts composition and
      antioxidant activity. Moreover, the influence of carotenoids and phenolic
      compounds on the antioxidant and anti-inflammatory activities of spinach extracts
      was also studied. RESULTS: The higher concentrations of carotenoids and the lower
      content of phenolic compounds were observed in the supercritical CO2 extracts;
      whereas water and/or ethanol PLE extracts presented low amounts of carotenoids
      and the higher concentrations of phenolic compounds. PLE extract with the highest
      content of phenolic compounds showed the highest antioxidant activity, although
      SFE carotenoid rich extract also showed a high antioxidant activity. Moreover,
      both extracts presented an important anti-inflammatory activity. CONCLUSION: PLE
      seems to be a good technique for the extraction of antioxidant and anti
      inflammatory compounds from spinach leaves. Moreover, spinach phenolic compounds
      and carotenoids present a high antioxidant activity, whereas spinach carotenoids
      seem to show a higher anti-inflammatory activity than phenolic compounds. It is
      worth noting that of our knowledge this is the first time the anti-inflammatory
      activity of lipophilic extracts from spinach leaves is reported.

PMID- 24930818
TI  - Divorce, approaches to learning, and children's academic achievement: a
      longitudinal analysis of mediated and moderated effects.
AB  - Data from the Early Childhood Longitudinal Study--Kindergarten Cohort (ECLS-K)
      were used to test the hypothesis that approaches to learning (ATL) mediates the
      link between parental divorce and academic achievement. Fixed effects regression
      was utilized to test for mediation, and subsequent moderation analyses examining
      gender and age at time of divorce also were conducted. Results indicated that
      divorce was associated with less growth in test scores and that ATL mediated 18%
      and 12% of this association in reading and mathematics respectively. Parental
      divorce also was associated with larger negative effects for children who
      experienced divorce at an older age as well as for girls' mathematics test
      scores. These findings contribute to the understanding of the impact of parental
      divorce on children's academic achievement and underscore the importance of
      focusing on the variability of child outcomes following parental divorce.

PMID- 24930817
TI  - No effect of weight loss on LINE-1 methylation levels in peripheral blood
      leukocytes from postmenopausal overweight women.
AB  - OBJECTIVES: Obesity and weight-loss are associated with methylation patterns in
      specific genes, but their effect on Long Interspersed Nuclear Elements (LINE-1)
      methylation, a measure of global methylation is largely unknown. METHODS: Three
      hundred overweight/obese post-menopausal women (50-75 years) were part of a
      completed, 1-year randomized controlled trial, comparing independent and combined
      effects of a reduced-calorie weight-loss diet, and exercise program, versus
      control. DNA was extracted from peripheral blood leukocytes collected at baseline
      and 12-months, and LINE-1 methylation analyzed by pyrosequencing. Mean changes
      between groups using generalized estimating equations and examined effects of
      weight-loss on LINE-1 methylation using stratified analyses (gained weight/no
      weight-loss [N = 84]; <5% [N = 45]; 5%-10% [N = 45]; >10% of baseline weight-loss
      [N = 126]) within each arm, adjusted by blood cell counts were compared.
      Associations between LINE-1 methylation and previously measured biomarkers, and
      anthropometrics were also examined. RESULTS: No significant difference in LINE-1
      methylation levels was detected in any intervention group versus controls. The
      magnitude of weight-loss was not associated with LINE-1 methylation at 12-months.
      There were no associations between baseline characteristics of participants, or
      previously measured biomarkers, and LINE-1 methylation. CONCLUSIONS: Our results
      suggest that lifestyle changes sufficient to significantly reduce weight over 12
      months may not change LINE-1 DNA methylation levels.

PMID- 24930820
TI  - Early adolescents' willingness to intervene: what roles do attributions, affect,
      coping, and self-reported victimization play?
AB  - Limited research has sought to understand early adolescents' willingness to
      intervene in peer victimization as a function of their own responding to being
      victimized. The present study examined whether early adolescents' attributions,
      affect, and coping responses to a victimization vignette were related to their
      willingness to intervene, and whether self-reported victimization moderated the
      aforementioned associations. Participants were 653 5th- to 8th-grade students
      (50.4% girls, 58.5% Caucasian, 34.5% Hispanic) who completed a self-report survey
      that included a vignette asking students to imagine that they were victimized in
      school. Hierarchical regression analyses were conducted separately for boys and
      girls. Although attributions and affect showed no significant associations with
      students' willingness to intervene, seeking social support coping was associated
      with greater willingness to intervene for both boys and girls, and problem
      focused coping was associated with willingness to intervene for girls only.
      Unexpectedly, self-reported victimization was associated positively with both
      boys' and girls' willingness to intervene. Findings also revealed two unexpected
      two-way interactions between peer victimization and boys' characterological self
      blame and girls' wishful thinking coping. Overall, study findings highlight the
      need for future research and anti-bullying programs to address how victimization
      could either motivate or discourage a student's willingness to intervene. 

PMID- 24930821
TI  - A longitudinal multilevel model analysis of the within-person and between-person
      effect of effortful engagement and academic self-efficacy on academic
      performance.
AB  - Using data from an accelerated longitudinal study, we examined the within-person
      and between-person effect of effortful engagement and academic self-efficacy on
      academic performance across students (N=135) in elementary school. Teachers
      assessed participants' effortful engagement and participants rated their academic
      self-efficacy once per year for 3 years. Academic performance was assessed
      through standardized test scores in reading and math. Multilevel models indicated
      that within-person change in Effortful Engagement and Academic Self-Efficacy
      scores significantly predicted concomitant within-person change in reading test
      scores, B=2.71, p=.043, Pseudo-R2=.02 and B=4.72, p=.005, Pseudo-R2=.04,
      respectively. Participants with higher between-person levels of Effortful
      Engagement had higher initial reading test scores, B=10.03, p=.001, Pseudo
      R2=.09, and math test scores, B=11.20, p<.001, Pseudo-R2=.15, whereas
      participants with higher between-person levels of Academic Self-Efficacy showed a
      faster rate of increase in math test scores across elementary school, B=10.21,
      p=.036, Pseudo-R2=.25. At the between-person level, Effortful Engagement mediated
      the association between Academic Self-Efficacy and both reading and math test
      scores, although no support was found for mediation at the within-person level.
      Collectively, results suggest that trait-level psychological factors can vary
      meaningfully within school-aged children and that both within-person change and
      between-person individual differences in these traits have important consequences
      for academic performance.

PMID- 24930822
TI  - Effect of peer nominations of teacher-student support at individual and classroom
      levels on social and academic outcomes.
AB  - This longitudinal study examined the prospective relations between 713 elementary
      students' individual peer teacher support reputation (PTSR) and a measure of the
      classroom-wide dispersion of peer nominations of teacher support (Centralization
      of Teacher Support) on students' peer relatedness (i.e., peer acceptance and peer
      academic reputation) and academic motivation (i.e., academic self-efficacy and
      teacher-rated behavioral engagement). PTSR was measured as the proportion of
      classmates who nominated a given student on a descriptor of teacher-student
      support. Centralization of Teacher Support was assessed using social network
      analysis to identify the degree to which peer nominations of teacher support in a
      classroom centered on a few students. PTSR predicted changes in all student
      outcomes, above academic achievement and relevant covariates. Centralization of
      Teacher Support predicted changes in students' peer academic reputation, net the
      effect of PTSR and covariates. Students' academic achievement moderated effects
      of PTSR and Centralization of Teacher Support on some outcomes. Findings
      highlight the importance of peers' perceptions of teacher support and of the
      structure of those perceptions for children's social and academic outcomes.
      Implications for practice are discussed. 

PMID- 24930819
TI  - A randomized controlled pilot trial of classroom-based mindfulness meditation
      compared to an active control condition in sixth-grade children.
AB  - The current study is a pilot trial to examine the effects of a nonelective,
      classroom-based, teacher-implemented, mindfulness meditation intervention on
      standard clinical measures of mental health and affect in middle school children.
      A total of 101 healthy sixth-grade students (55 boys, 46 girls) were randomized
      to either an Asian history course with daily mindfulness meditation practice
      (intervention group) or an African history course with a matched experiential
      activity (active control group). Self-reported measures included the Youth Self
      Report (YSR), a modified Spielberger State-Trait Anxiety Inventory, and the
      Cognitive and Affective Mindfulness Measure -Revised. Both groups decreased
      significantly on clinical syndrome subscales and affect but did not differ in the
      extent of their improvements. Meditators were significantly less likely to
      develop suicidal ideation or thoughts of self-harm than controls. These results
      suggest that mindfulness training may yield both unique and non-specific benefits
      that are shared by other novel activities. 

PMID- 24930823
TI  - Developing school psychologists as agents of social justice: a qualitative
      analysis of student understanding across three years.
AB  - This study employed a cohort-sequential design with four cohorts over 3 years to
      investigate school psychology graduate trainees' (n=37) understanding of social
      justice. Using consensual qualitative research methods, participants'
      perspectives on social justice writ large, social justice as it applies to school
      psychology, and effective aspects of social justice training in their graduate
      training program were collected through semi-structured focus group interviews.
      Field-based training though service-learning in diverse communities provided
      trainees with exposure to experiences that were viewed as instrumental in their
      understanding of social justice in general and as it applies to school
      psychology. Trainees described aspects of the training program that were viewed
      as conducive to educating school psychologists as agents of social justice. Based
      on findings from the study, a descriptive model of school psychology training for
      social justice is proposed.

PMID- 24930825
TI  - Relationship between growth and standard metabolic rate: measurement artefacts
      and implications for habitat use and life-history adaptation in salmonids.
AB  - Mass-specific standard metabolic rate (SMR, or maintenance metabolism) varies
      greatly among individuals. Metabolism is particularly sensitive to variation in
      food consumption and growth creating the potential for significant bias in
      measured SMR for animals that are growing (e.g. juveniles) or of uncertain
      nutritional status. Consequently, interpreting individual variation in metabolism
      requires a sound understanding of the potentially confounding role of growth and
      the relative importance of fixed (genetic) vs. environmental drivers of SMR
      variation. We review the role of growth in measured SMR variation in juvenile
      salmonids, with the goals of (i) understanding the contribution of growth (and
      food consumption) to SMR variation through ontogeny, (ii) understanding the
      relative contributions of tissue maintenance and biosynthesis (overhead costs of
      growth) to apparent SMR variation, and (iii) using intrinsic growth effects on
      SMR to model how alternate life-history strategies may influence growth and
      measured SMR in juvenile salmonids. SMR measures on juveniles, even when post
      absorptive, may be inflated by delayed growth-associated overhead costs, unless
      juveniles are on a maintenance ration (i.e. not growing). Empirical measurements
      of apparent SMR in food restricted vs. satiated 2-5 g juvenile salmon demonstrate
      that estimates may be inflated by as much as 67% due to delayed overhead costs of
      growth, even when SMR measurements are taken 35 h post-feeding. These results
      indicate that a substantial component of variation in apparent SMR among juvenile
      salmonids may be associated with (i) environmentally driven variation in ration
      (where elevated SMR measurements are an artefact of delayed growth overhead
      costs), (ii) intrinsic (genetic) or plastic organ-system trade-offs related to
      increasing investment in metabolically expensive digestive tissue responsible for
      processing food and (iii) intrinsic (genetic) variation in maximum body size and
      growth among individuals or life-history types. We suggest that selection for
      differences in adult body size among resident and anadromous forms leading to
      differences in juvenile growth trajectories may contribute to both SMR variation
      and habitat segregation in freshwater, where juveniles with higher growth are
      constrained to foraging in high velocity habitats to meet their greater
      consumption needs. 

PMID- 24930826
TI  - Validity, reliability, and assessment sensitivity of the Japanese version of the
      short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and
      non-neuropathic pain.
AB  - OBJECTIVE: The objective of this study was to define the validity, reliability,
      and assessment sensitivity of the Japanese version of the Short-Form McGill Pain
      Questionnaire 2 (SF-MPQ-2-J). DESIGN: This is a cross-sectional study. PATIENTS
      AND METHODS: The original SF-MPQ-2 was translated into Japanese to create the SF
      MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese
      patients was validated. The reliability of the SF-MPQ-2-J was assessed using
      internal consistency, reliability coefficients (Cronbach's alpha), and
      reproducibility coefficients (intraclass correlation coefficient) obtained using
      234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on
      associations identified between total and subscale scores compared with other
      assessment methods. A confirmatory factor analysis (CFA) was also performed to
      test the theoretical structure of the SF-MPQ-2-J. RESULTS: The internal
      consistencies calculated included continuous pain, alpha=0.893; intermittent
      pain, alpha=0.875; predominantly neuropathic pain, alpha=0.917; affective
      descriptors, alpha=0.857; and total score, alpha=0.907. The reproducibility
      coefficients calculated included continuous pain, rho=0.81; intermittent pain,
      rho=0.78; predominantly neuropathic pain, rho=0.85; affective descriptors,
      rho=0.75; and total score, rho=0.83. The CFA showed that the model fit of the
      readily interpretable subscales was acceptable, and the goodness of fit index
      value was 0.917. In addition, the mean predominantly neuropathic pain subscale
      score was found to be significantly higher for patients with neuropathic pain vs
      non-neuropathic pain. CONCLUSION: These findings suggest that the reliability and
      validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross
      cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for
      research and clinical use, and for discriminating neuropathic pain from non
      neuropathic pain.

PMID- 24930824
TI  - Acquired resistance to selective estrogen receptor modulators (SERMs) in clinical
      practice (tamoxifen & raloxifene) by selection pressure in breast cancer cell
      populations.
AB  - Tamoxifen, a pioneering selective estrogen receptor modulator (SERM), has long
      been a therapeutic choice for all stages of estrogen receptor (ER)-positive
      breast cancer. The clinical application of long-term adjuvant antihormone therapy
      for the breast cancer has significantly improved breast cancer survival. However,
      acquired resistance to SERM remains a significant challenge in breast cancer
      treatment. The evolution of acquired resistance to SERMs treatment was primarily
      discovered using MCF-7 tumors transplanted in athymic mice to mimic years of
      adjuvant treatment in patients. Acquired resistance to tamoxifen is unique
      because the growth of resistant tumors is dependent on SERMs. It appears that
      acquired resistance to SERM is initially able to utilize either E2 or a SERM as
      the growth stimulus in the SERM-resistant breast tumors. Mechanistic studies
      reveal that SERMs continuously suppress nuclear ER-target genes even during
      resistance, whereas they function as agonists to activate multiple membrane
      associated molecules to promote cell growth. Laboratory observations in vivo
      further show that three phases of acquired SERM-resistance exists, depending on
      the length of SERMs exposure. Tumors with Phase I resistance are stimulated by
      both SERMs and estrogen. Tumors with Phase II resistance are stimulated by SERMs,
      but are inhibited by estrogen due to apoptosis. The laboratory models suggest a
      new treatment strategy, in which limited-duration, low-dose estrogen can be used
      to purge Phase II-resistant breast cancer cells. This discovery provides an
      invaluable insight into the evolution of drug resistance to SERMs, and this
      knowledge is now being used to justify clinical trials of estrogen therapy
      following long-term antihormone therapy. All of these results suggest that cell
      populations that have acquired resistance are in constant evolution depending
      upon selection pressure. The limited availability of growth stimuli in any new
      environment enhances population plasticity in the trial and error search for
      survival. 

PMID- 24930827
TI  - Mixed reverse micelles facilitated downstream processing of lipase involving
      water-oil-water liquid emulsion membrane.
AB  - Our earlier work for the first time demonstrated that liquid emulsion membrane
      (LEM) containing reverse micelles could be successfully used for the downstream
      processing of lipase from Aspergillus niger. In the present work, we have
      attempted to increase the extraction and purification fold of lipase by using
      mixed reverse micelles (MRM) consisting of cationic and nonionic surfactants in
      LEM. It was basically prepared by addition of the internal aqueous phase solution
      to the organic phase followed by the redispersion of the emulsion in the feed
      phase containing enzyme, which resulted in globules of water-oil-water (WOW)
      emulsion for the extraction of lipase. The optimum conditions for maximum lipase
      recovery (100%) and purification fold (17.0-fold) were CTAB concentration 0.075
      M, Tween 80 concentration 0.012 M, at stirring speed of 500 rpm, contact time 15
      min, internal aqueous phase pH 7, feed pH 9, KCl concentration 1 M, NaCl
      concentration 0.1 M, and ratio of membrane emulsion to feed volume 1:1.
      Incorporation of the nonionic surfactant (e.g., Tween 80) resulted in remarkable
      improvement in the purification fold (3.1-17.0) of the lipase. LEM containing a
      mixture of nonionic and cationic surfactants can be successfully used for the
      enhancement in the activity recovery and purification fold during downstream
      processing of enzymes/proteins.

PMID- 24930828
TI  - Synthesis of (11)C-labeled retinoic acid, [(11)C]ATRA, via an alkenylboron
      precursor by Pd(0)-mediated rapid C-[(11)C]methylation.
AB  - Retinoids are a class of chemical compounds which include both natural dietary
      vitamin A (retinol) metabolites and active synthetic analogs. Both experimental
      and clinical studies have revealed that retinoids regulate a wide variety of
      essential biological processes. In this study, we synthesized (11)C-labeled all
      trans-retinoic acid (ATRA), the most potent biologically active metabolite of
      retinol and used in the treatment of acute promyelocytic leukemia. The synthesis
      of (11)C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C
      [(11)C]methylation of the corresponding pinacol borate precursor prepared by 8
      steps and hydrolysis. [(11)C]ATRA will prove useful as a PET imaging agent,
      particularly for elucidating the improved therapeutic activity of ATRA (natural
      retinoid) for acute promyelocytic leukemia by comparing with the corresponding
      PET probe [(11)C]Tamibarotene (artificial retinoid). 

PMID- 24930830
TI  - Complanadine A, a selective agonist for the Mas-related G protein-coupled
      receptor X2.
AB  - The first biological target for the natural product complanadine A has been
      determined. The pseudosymmetric alkaloid functions as a selective agonist for the
      Mas-related G protein-coupled receptor X2 (MrgprX2), a G protein-coupled receptor
      that is highly expressed in neurons. Given the potential of MrgprX2 to function
      as a modulator of pain, complanadine A represents a new chemical probe to
      selectively interrogate the physiological function of MrgprX2 as well as a
      potential lead for the development of antihyperalgesics for the treatment of
      persistent pain. While complanadine A possess agonistic activity the related
      natural product lycodine, representing half of complanadine A, lacks activity
      providing a cursory description of the structural requirements for agonistic
      activity. 

PMID- 24930829
TI  - 2-Aminobenzoxazole ligands of the hepatitis C virus internal ribosome entry site.
AB  - 2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus
      (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to
      explore the less basic benzoxazole system as a replacement for the core scaffold
      in previously discovered benzimidazole viral translation inhibitors. Structure
      activity relationships in the target binding of substituted benzoxazole ligands
      were investigated. 

PMID- 24930831
TI  - [(11)C-carbonyl]CEP-32496: radiosynthesis, biodistribution and PET study of brain
      uptake in P-gp/BCRP knockout mice.
AB  - CEP-32496 is a novel, orally active serine/threonine-protein kinase B-raf (BRAF)
      (V600E) kinase inhibitor that is being investigated in clinical trials for the
      treatment of some cancers in patients. In this study, we developed [(11)C
      carbonyl]CEP-32496 as a novel positron emission tomography (PET) probe to study
      its biodistribution in the whole bodies of mice. [(11)C]CEP-32496 was synthesized
      by the reaction of 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine
      hydrochloride (1.HCl) with [(11)C]phosgene, followed by treatment with 3-(6,7
      dimethoxyquinozolin-4-yloxy)aniline (2). Small-animal PET studies with [(11)C]CEP
      32496 indicated that radioactivity levels (AUC0-90 min, SUV*min) accumulated in
      the brains of P-gp/BCRP knockout mice at a 8-fold higher rate than in the brains
      of wild-type mice.

PMID- 24930832
TI  - Efficient synthesis of eudistomin U and evaluation of its cytotoxicity.
AB  - Eudistomin U is a member of a subclass of naturally occurring indole alkaloids
      known as beta-carbolines. These molecules are reported to have diverse biological
      activity and high binding affinity to DNA, which make them attractive targets for
      total synthesis. We describe an efficient, five-step synthesis of eudistomin U by
      employing two key reactions: a Bischler-Napieralski cyclization and a Suzuki
      cross coupling. We also describe the cytotoxicity of eudistomin U against various
      cancer cell lines and human pathogens, in which we observed potent antibacterial
      activity against Gram-positive bacteria. 

PMID- 24930833
TI  - Synthesis and structure-activity relationships of 4-fluorophenyl-imidazole
      p38alpha MAPK, CK1delta and JAK2 kinase inhibitors.
AB  - The synthesis and structure-activity relationships of novel 4-(4'
      fluorophenyl)imidazoles as selective p38alpha MAPK, CK1delta and JAK2 inhibitors
      with improved water solubility are described. Microwave-assisted multicomponent
      reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and
      phosphonate groups were introduced via 'click' reactions. The kinase selectivity
      was influenced by the heteroaryl group at imidazole C-5 and the position of a
      carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34
      inhibited p38alpha MAPK with IC50=250 nM and 96 nM, respectively. Pyridine 3 gave
      CK1delta inhibition with IC50=89 nM and pyridin-2-one 31 gave JAK2 inhibition
      with IC50=62 nM.

PMID- 24930835
TI  - Synthesis of new melatoninergic hexahydroindenopyridines.
AB  - Hexahydroindenopyridine (HHIP) is an interesting heterocyclic framework that
      contains an indene core similar to ramelteon. This type of tricyclic piperidines
      aroused our interest as potential melatoninergic ligands. Melatonin receptor
      ligands have applications in insomnia and depression. We report herein an
      efficient two-step method to prepare new HHIP by the reaction of an enamine with
      3-bromopropylamine hydrobromide. Some synthesized compounds showed moderate
      affinity for melatonin receptors in the nanomolar or low micromolar range.
      Furthermore, the methylenedioxy HHIPs 2d (N-phenylacetamide) and 2f (N,N
      diethylacetamide), exhibited high selectivity at MT1 or MT2 receptors,
      respectively, when compared with melatonin. It seems that the methylenedioxy
      group on the indene ring system and the N-acetamide substituent are important
      structural features to bind selectively MT1 or MT2 subtypes. 

PMID- 24930834
TI  - Halogenated diarylacetylenes repress c-myc expression in cancer cells.
AB  - Halogenated diarylacetylenes that possess fluorine or chlorine substituents in
      one aryl ring and N-methylamino or N,N-dimethylamino in the other aryl ring
      inhibit the proliferation of LS174T colon cancer cells through the repression of
      c-myc expression and induction of the cyclin-dependent kinase inhibitor-1 (i.e.,
      p21(Wif1/Cip1)) and represent potentially useful antineoplastic agents. 

PMID- 24930836
TI  - Synthesis and bioactive evaluation of a novel series of coumarinazoles.
AB  - A series of novel coumarinazoles were designed, synthesized, and characterized by
      IR, NMR, MS and HRMS spectra. The bioactive assay for the newly prepared
      compounds against six bacteria and five fungi manifested that most new compounds
      exhibited good or even stronger antibacterial and antifungal activities in
      comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. Bis
      azole alcohols 7a and 7d-e showed better anti-Candida utilis activity than mono
      azole derivatives 4a and 4d-e at the tested concentrations, and they were more
      potent than the clinical Fluconazole. While triazole alcohol 7a gave comparable
      anti-Candida albicans and anti-Candida mycoderma activity to Fluconazole and
      better anti-MRSA activity than mono-triazole one 4a and clinical Norfloxacin. 1H
      Benzoimidazol-2-ylthio coumarin derivatives 4e and 7e gave the strongest anti
      Escherichia coli JM109 efficacy. Oxiran-2-ylmethoxy moiety was found to be a
      beneficial fragment to improve antibacterial and antifungal activity to some
      extent. 

PMID- 24930837
TI  - Dielectrophoretic separation of micron and submicron particles: a review.
AB  - This paper provides an overview on separation of micron and submicron sized
      biological (cells, yeast, virus, bacteria, etc.) and nonbiological particles
      (latex, polystyrene, CNTs, metals, etc.) by dielectrophoresis (DEP), which finds
      wide applications in the field of medical and environmental science. Mathematical
      models to predict the electric field, flow profile, and concentration profiles of
      the particles under the influence of DEP force have also been covered in this
      review. In addition, advancements made primarily in the last decade, in the area
      of electrode design (shape and arrangement), new materials for electrode (carbon,
      silicon, polymers), and geometry of the microdevice, for efficient DEP separation
      of particles have been highlighted.

PMID- 24930838
TI  - Long-term outcome of segmental reconstruction of the humeral head for the
      treatment of locked posterior dislocation of the shoulder.
AB  - BACKGROUND: Locked posterior glenohumeral dislocations with impaction fractures
      involving less than 30% to 35% of the humeral head are most frequently treated
      with lesser tuberosity transfer into the defect, whereas those involving more
      than 35% to 40% are treated with humeral head arthroplasty. As an alternative,
      reconstruction of the defect with segmental femoral or humeral head allograft has
      been proposed, but the long-term outcome of this joint-preserving procedure is
      unknown. METHODS: Twenty-two shoulders in 21 patients with a locked posterior
      shoulder dislocation and an impaction of at least 30% (mean, 43%) of the humeral
      head were treated with segmental reconstruction of the humeral head defect. They
      were reviewed clinically and radiographically at a minimum follow-up of 5 years.
      RESULTS: Of the 22 shoulders, 19 could be followed up at 128 months (range, 60
      294 months) postoperatively. Only 2 of the 19 patients needed a prosthesis more
      than 180 months after the index operation. Of the other 17, 4 had
      radiographically advanced osteoarthritis (OA), 4 had mild OA, and 9 had no or
      minimal OA. Eighteen shoulders were rated as subjectively excellent, none were
      rated as good, and one was rated as fair. The final Constant-Murley score
      averaged 77 points (range, 52-98 points), the Subjective Shoulder Value averaged
      88% (range, 75%-100%), and only 2 patients had mild to moderate pain. Mean active
      anterior elevation was 145 degrees , and mean external rotation with the arm at
      the side was 42 degrees . CONCLUSION: Segmental reconstruction of humeral head
      defects for large anteromedial impaction fractures caused by locked posterior
      dislocations durably restores stability and freedom from pain with an excellent
      subjective long-term outcome.

PMID- 24930839
TI  - Arthroscopic anatomic glenoid reconstruction using an autologous iliac crest bone
      grafting technique.
AB  - BACKGROUND: Open bone block procedures for glenohumeral stabilization have been
      used for a long time. With the advancement of arthroscopic techniques and the
      development of sophisticated instruments and implants, the insertion of the bone
      block can be performed by an all-arthroscopic approach. The purpose of this study
      was to evaluate the clinical and radiologic results after an arthroscopic
      anatomic glenoid reconstruction using an all-arthroscopic, autologous tricortical
      iliac crest bone grafting technique. MATERIALS AND METHODS: Fifteen patients (1
      female and 14 male patients; mean age, 31.4 years [range, 17-49 years]) underwent
      reconstruction of significant glenoid defects in cases of recurrent shoulder
      instability by the aforementioned technique. The patients were followed up
      clinically (range of motion, Constant score, Rowe score, Subjective Shoulder
      Value, and Western Ontario Shoulder Instability Index) and radiographically (with
      true anteroposterior and axillary views, as well as 2-/3-dimensional computed
      tomography [glenoid configuration, signs of graft resorption, bone consolidation,
      and glenoid index]). RESULTS: After a mean follow-up period of 20.6 months
      (range, 12-65 months), the Constant score averaged 85.0 points (range, 73-98
      points; contralateral side, 89.6 points [range, 78-96 points]), the Rowe score
      averaged 88.0 points (range, 65-100 points), the Subjective Shoulder Value
      averaged 84.5% (range, 50%-100%), and the Western Ontario Shoulder Instability
      Index averaged 76.7% (range, 46%-93%). No recurrent subluxations or dislocations
      were observed. Radiographically, computed tomography imaging showed a
      consolidated autograft in all cases. The glenoid index increased from a mean of
      0.77 preoperatively to 1.16 immediately postoperatively; at the time of last
      follow-up, the glenoid index decreased to 1.04. CONCLUSION: The arthroscopic
      reconstruction of anteroinferior glenoid defects re-creates the pear-shaped
      anatomy of the anteroinferior glenoid and leads to good to excellent early
      clinical results.

PMID- 24930840
TI  - Establishing an international shoulder arthroplasty consortium.

PMID- 24930842
TI  - Additive effects of maternal iron deficiency and prenatal immune activation on
      adult behaviors in rat offspring.
AB  - Both iron deficiency (ID) and infection are common during pregnancy and studies
      have described altered brain development in offspring as a result of these
      individual maternal exposures. Given their high global incidence, these two
      insults may occur simultaneously during pregnancy. We recently described a rat
      model which pairs dietary ID during pregnancy and prenatal immune activation.
      Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day
      2 (E2) until postnatal day 7, and administered the bacterial endotoxin,
      lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration
      on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6
      and tumor necrosis factor-alpha, in ID dams compared to IS dams. This suggested
      that the combination of prenatal immune activation on a background of maternal ID
      might have more adverse neurodevelopmental consequences for the offspring than
      exposure to either insult alone. In this study we used this model to determine
      whether combined exposure to maternal ID and prenatal immune activation interact
      to affect juvenile and adult behaviors in the offspring. We assessed behaviors
      relevant to deficits in humans or animals that have been associated with exposure
      to either maternal ID or prenatal immune activation alone. Adult offspring from
      ID dams displayed significant deficits in pre-pulse inhibition of acoustic
      startle and in passive avoidance learning, together with increases in cytochrome
      oxidase immunohistochemistry, a marker of metabolic activity, in the ventral
      hippocampus immediately after passive avoidance testing. Offspring from LPS
      treated dams showed a significant increase in social behavior with unfamiliar
      rats, and subtle locomotor changes during exploration in an open field and in
      response to amphetamine. Surprisingly, there was no interaction between effects
      of the two insults on the behaviors assessed, and few observed alterations in
      juvenile behavior. Our findings show that long-term effects of maternal ID and
      prenatal LPS were additive, such that offspring exposed to both insults displayed
      more adult behavioral abnormalities than offspring exposed to one alone. 

PMID- 24930841
TI  - Manganese accumulation in bone following chronic exposure in rats: steady-state
      concentration and half-life in bone.
AB  - Literature data indicate that bone is a major storage organ for manganese (Mn),
      accounting for 43% of total body Mn. However, the kinetic nature of Mn in bone,
      especially the half-life (t(1/2)), remained unknown. This study was designed to
      understand the time-dependence of Mn distribution in rat bone after chronic oral
      exposure. Adult male rats received 50 mg Mn/kg (as MnCl2) by oral gavage, 5 days
      per week, for up to 10 weeks. Animals were sacrificed every 2 weeks during Mn
      administration for the uptake study, and on day 1, week 2, 4, 8, or 12 after the
      cessation at 6-week Mn exposure for the t(1/2) study. Mn concentrations in bone
      (MnBn) were determined by AAS analysis. By the end of 6-week's treatment, MnBn
      appeared to reach the steady state (T(ss)) level, about 2-3.2 fold higher than
      MnBn at day 0. Kinetic calculation revealed t(1/2)s of Mn in femur, tibia, and
      humerus bone of 77 (r=0.978), 263 (r=0.988), and 429 (r=0.994) days,
      respectively; the average t(1/2) in rat skeleton was about 143 days, equivalent
      to 8.5 years in human bone. Moreover, MnBn were correlated with Mn levels in
      striatum, hippocampus, and CSF. These data support MnBn to be a useful biomarker
      of Mn exposure.

PMID- 24930843
TI  - Reply to: alimentary, my dear Watson? The challenges of enteric alpha-synuclein
      as a Parkinson's disease biomarker.

PMID- 24930844
TI  - Molecular characterization of anaerobic sulfur-oxidizing microbial communities in
      up-flow anaerobic sludge blanket reactor treating municipal sewage.
AB  - A novel wastewater treatment system consisting of an up-flow anaerobic sludge
      blanket (UASB) reactor and a down-flow hanging sponge (DHS) reactor with sulfur
      redox reaction was developed for treatment of municipal sewage under low
      temperature conditions. In the UASB reactor, a novel phenomenon of anaerobic
      sulfur oxidation occurred in the absence of oxygen, nitrite and nitrate as
      electron acceptors. The microorganisms involved in anaerobic sulfur oxidation
      have not been elucidated. Therefore, in this study, we studied the microbial
      communities existing in the UASB reactor that probably enhanced anaerobic sulfur
      oxidation. Sludge samples collected from the UASB reactor before and after sulfur
      oxidation were used for cloning and terminal restriction fragment length
      polymorphism (T-RFLP) analysis of the 16S rRNA genes of the bacterial and
      archaeal domains. The microbial community structures of bacteria and archaea
      indicated that the genus Smithella and uncultured bacteria within the phylum
      Caldiserica were the dominant bacteria groups. Methanosaeta spp. was the dominant
      group of the domain archaea. The T-RFLP analysis, which was consistent with the
      cloning results, also yielded characteristic fingerprints for bacterial
      communities, whereas the archaeal community structure yielded stable microbial
      community. From these results, it can be presumed that these major bacteria
      groups, genus Smithella and uncultured bacteria within the phylum Caldiserica,
      probably play an important role in sulfur oxidation in UASB reactors. 

PMID- 24930846
TI  - Kernohan-Woltman notch phenomenon.

PMID- 24930845
TI  - Contribution of CT scan and CT-guided aspiration in the management of
      retropharyngeal abscess in children based on a series of 18 cases.
AB  - OBJECTIVE: This study was designed to analyse the contribution of CT scan to the
      management of retropharyngeal abscess in children and the place of CT-guided
      percutaneous aspiration as an alternative to surgical drainage. MATERIALS AND
      METHODS: Retrospective study including 18 children with a mean age of 38 months
      [range: 5-67 months] presenting with retropharyngeal infection between 2006 and
      2011. All cases were initially assessed by contrast-enhanced CT scan of the neck.
      Clinical, radiological treatment and bacteriological data were collected.
      Radiological results were correlated with surgical and percutaneous aspiration
      findings (presence or absence of an abscess). RESULTS: The initial CT scan
      detected 14 abscesses, 3 cases of non-suppurative lymphadenitis and one case of
      retropharyngeal oedema. One case of non-suppurative lymphadenitis progressed to
      abscess after failure of antibiotic therapy and was treated surgically. Surgical
      drainage revealed a purulent collection in 11 cases and no collection in 3 cases.
      Four CT-guided percutaneous aspirations were successfully performed. Three cases
      were treated by antibiotics alone (2 cases of lymphadenitis and 1 case of
      retropharyngeal oedema). Bacteriological examinations revealed the presence of
      Streptococcus pyogenes in 78.5% of cases. The positive predictive value of the
      initial CT scan was 78.8% in our series. CONCLUSION: Contrast-enhanced neck CT
      scan confirmed the diagnosis of retropharyngeal abscess and the indication for
      surgical drainage. It must be performed urgently, on admission. When it is
      decided to treat the patient with antibiotics alone, follow-up imaging should be
      performed in the absence of improvement 24 to 48 hours after starting
      antibiotics. CT-guided percutaneous aspiration is both a diagnostic modality
      confirming abscess formation of an inflammatory lesion of the retropharyngeal
      space as well as a therapeutic tool, sometimes avoiding the need for surgical
      drainage.

PMID- 24930847
TI  - Amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of
      antimalarial drugs.
AB  - It can be foreseen that in a future scenario of malaria eradication, a varied
      armamentarium will be required, including strategies for the targeted
      administration of antimalarial compounds. The development of nanovectors capable
      of encapsulating drugs and of delivering them to Plasmodium-infected cells with
      high specificity and efficacy and at an affordable cost is of particular
      interest. With this objective, dendritic derivatives based on 2,2
      bis(hydroxymethyl)propionic acid (bis-MPA) and Pluronic((r)) polymers have been
      herein explored. Four different dendritic derivatives have been tested for their
      capacity to encapsulate the antimalarial drugs chloroquine (CQ) and primaquine
      (PQ), their specific targeting to Plasmodium-infected red blood cells (pRBCs),
      and their antimalarial activity in vitro against the human pathogen Plasmodium
      falciparum and in vivo against the rodent malaria species Plasmodium yoelii. The
      results obtained have allowed the identification of two dendritic derivatives
      exhibiting specific targeting to pRBCs vs. non-infected RBCs, which reduce the in
      vitro IC50 of CQ and PQ by ca. 3- and 4-fold down to 4.0 nm and 1.1 MUm,
      respectively. This work on the application of dendritic derivatives to
      antimalarial targeted drug delivery opens the way for the use of this new type of
      chemicals in future malaria eradication programs. 

PMID- 24930849
TI  - Silk fibroin layer-by-layer microcapsules for localized gene delivery.
AB  - Herein, we describe the delivery of plasmid DNA (pDNA) using silk fibroin (SF)
      layer-by-layer assembled microcapsules. Deposition of fluorescently labeled SF
      onto polystyrene (PS) template particles resulted in increasing fluorescence
      intensity and decreasing surface charge in correlation to SF layer number. After
      removal of the PS core, hollow, monodisperse, and structurally stable SF
      microcapsules of variable size and shell thickness were obtained. Plasmid DNA
      encoding for enhanced green fluorescent protein (eGFP) was loaded onto 1 or 4 MUm
      capsules, either by incorporation of pDNA within the innermost layer of the shell
      or by adsorption to the microcapsules surface, and in vitro pDNA release,
      cytotoxicty and eGFP expression were studied. Sustained pDNA release over 3 days
      was observed using both loading techniques, being accelerated in the presence of
      protease. DNA loaded SF microcapsules resulted in efficient cell transfection
      along with low cytotoxicity after 3 days incubation compared to treatment with
      pDNA/branched polyethylenimine complexes. Among the tested conditions highest
      transfection efficiencies were achieved using 1 MUm capsules where pDNA was
      adsorbed to the capsule surface. Our results suggest that SF microcapsules are
      suitable for the localized delivery of pDNA, combining low cytotoxicity and high
      transfection efficiency. 

PMID- 24930848
TI  - Magnetization transfer contrast MRI for non-invasive assessment of innate and
      adaptive immune responses against alginate-encapsulated cells.
AB  - By means of physical isolation of cells inside semi-permeable hydrogels,
      encapsulation has been widely used to immunoprotect transplanted cells. While
      spherical alginate microcapsules are now being used clinically, there still is
      little known about the patient's immune system response unless biopsies are
      obtained. We investigated the use of Magnetization Transfer (MT) imaging to non
      invasively detect host immune responses against alginate capsules containing
      xenografted human hepatocytes in four groups of animals, including transplanted
      empty capsules (-Cells/-IS), capsules with live cells with (+LiveCells/+IS) and
      without immunosuppression (+LiveCells/-IS), and capsules with apoptotic cells in
      non-immunosuppressed animals (+DeadCells/-IS). The highest MT ratio (MTR) was
      found in +LiveCells/-IS, which increased from day 0 by 38% and 53% on days 7 and
      14 after transplantation respectively, and corresponded to a distinctive increase
      in cell infiltration on histology. Furthermore, we show that macromolecular ratio
      maps based on MT data are more sensitive to cell infiltration and fibrosis than
      conventional MTR maps. Such maps showed a significant difference between
      +LiveCells/-IS (0.18 +/- 0.02) and +DeadCells/-IS (0.13 +/- 0.02) on day 7 (P <
      0.01) existed, which was not observed on MTR imaging. We conclude that MT
      imaging, which is clinically available, can be applied for non-invasive
      monitoring of the occurrence of a host immune response against encapsulated
      cells. 

PMID- 24930850
TI  - Intracellular redox-activated anticancer drug delivery by functionalized hollow
      mesoporous silica nanoreservoirs with tumor specificity.
AB  - In this study, a type of intracellular redox-triggered hollow mesoporous silica
      nanoreservoirs (HMSNs) with tumor specificity was developed in order to deliver
      anticancer drug (i.e., doxorubicin (DOX)) to the target tumor cells with high
      therapeutic efficiency and reduced side effects. Firstly, adamantanamine was
      grafted onto the orifices of HMSNs using a redox-cleavable disulfide bond as an
      intermediate linker. Subsequently, a synthetic functional molecule, lactobionic
      acid-grafted-beta-cyclodextrin (beta-CD-LA), was immobilized on the surface of
      HMSNs through specific complexation with the adamantyl group, where beta-CD
      served as an end-capper to keep the loaded drug within HMSNs. beta-CD-LA on HMSNs
      could also act as a targeting agent towards tumor cells (i.e., HepG2 cells),
      since the lactose group in beta-CD-LA is a specific ligand binding with the
      asialoglycoprotein receptor (ASGP-R) on HepG2 cells. In vitro studies
      demonstrated that DOX-loaded nanoreservoirs could be selectively endocytosed by
      HepG2 cells, releasing therapeutic DOX into cytoplasm and efficiently inducing
      the apoptosis and cell death. In vivo investigations further confirmed that DOX
      loaded nanoreservoirs could permeate into the tumor sites and actively interact
      with tumor cells, which inhibited the tumor growth with the minimized side
      effect. On the whole, this drug delivery system exhibits a great potential as an
      efficient carrier for targeted tumor therapy in vitro and in vivo. 

PMID- 24930851
TI  - Collagen scaffolds modified with CNTF and bFGF promote facial nerve regeneration
      in minipigs.
AB  - Most experiments of peripheral nerve repair after injury have been conducted in
      the rodent model but the translation of findings from rodent studies to clinical
      practice is needed partly because the nerve regeneration must occur over much
      longer distances in humans than in rodents. The reconstruction of long distance
      nerve injuries still represents a great challenge to surgeons who is engaged in
      peripheral nerve surgery. Here we used the functional nerve conduit (collagen
      scaffolds incorporated with neurocytokines CNTF and bFGF) to bridge a 35 mm long
      facial nerve gap in minipig models. At 6 months after surgery, electrophysiology
      assessment and histological examination were conducted to evaluate the
      regeneration of peripheral facial nerves. Based on functional and histological
      observations, the results indicated that the functional collagen scaffolds
      promoted nerve reconstruction. The number and arrangement of regenerated nerve
      fibers, myelination, and nerve function reconstruction was better in the CNTF +
      bFGF conduit group than the single factor CNTF or bFGF conduit group. The
      functional composite conduit, which exhibited favorable mechanical properties,
      may promote facial nerve regeneration in minipigs effectively. 

PMID- 24930853
TI  - The importance of three-dimensional scaffold structure on stemness maintenance of
      mouse embryonic stem cells.
AB  - Revealing the mechanisms of cell fate regulation is important for scientific
      research and stem cell-based therapy. The traditional two-dimensional (2D)
      cultured mES cells are in a very different 2D niche from the in vivo equivalent
      inner cell mass (ICM). Because the cell fate decision could be regulated by many
      cues which could be impacted by geometry, the traditional 2D culture system would
      hamper us from understanding the in vivo situations correctly. Three-dimensional
      (3D) scaffold was believed to provide a 3D environment closed to the in vivo one.
      In this work, three different scaffolds were prepared for cell culture. Several
      characters of mES cells were changed under 3D scaffolds culture compared to 2D,
      and these changes were mainly due to the alteration in geometry but not the
      matrix. The self-renewal of mES cells was promoted by the introducing of
      dimensionality. The stemness maintenance of mES was supported by all three 3D
      scaffolds without feeder cells in the long-time culture. Our findings
      demonstrated that the stemness maintenance of mES cells was promoted by the 3D
      geometry of scaffolds and this would provide a promising platform for ES cell
      research. 

PMID- 24930852
TI  - Inhibition of apoptosis in human induced pluripotent stem cells during expansion
      in a defined culture using angiopoietin-1 derived peptide QHREDGS.
AB  - Adhesion molecule signaling is critical to human pluripotent stem cell (hPSC)
      survival, self-renewal, and differentiation. Thus, hPSCs are grown as clumps of
      cells on feeder cell layers or poorly defined extracellular matrices such as
      Matrigel. We sought to define a small molecule that would initiate adhesion-based
      signaling to serve as a basis for a defined substrate for hPSC culture. Soluble
      angiopoeitin-1 (Ang-1)-derived peptide QHREDGS added to defined serum-free media
      increased hPSC colony cell number and size during long- and short-term culture
      when grown on feeder cell layers or Matrigel, i.e. on standard substrates,
      without affecting hPSC morphology, growth rate or the ability to differentiate
      into multiple lineages both in vitro and in vivo. Importantly, QHREDGS treatment
      decreased hPSC apoptosis during routine passaging and single-cell dissociation.
      Mechanistically, the interaction of QHREDGS with beta1-integrins increased
      expression of integrin-linked kinase (ILK), increased expression and activation
      of extracellular signal-regulated kinases 1/2 (ERK1/2), and decreased caspase-3/7
      activity. QHREDGS immobilization to polyethylene glycol hydrogels significantly
      increased cell adhesion in a dose-dependent manner. We propose QHREDGS as a small
      molecule inhibitor of hPSC apoptosis and the basis of an affordable defined
      substrate for hPSC maintenance. 

PMID- 24930855
TI  - Laryngeal cleft: Diagnosis and endoscopic surgical treatment. Report of 2 cases.

PMID- 24930854
TI  - Actively-targeted polyion complex micelles stabilized by cholesterol and
      disulfide cross-linking for systemic delivery of siRNA to solid tumors.
AB  - For small interfering RNA (siRNA)-based cancer therapies, we report an actively
      targeted and stabilized polyion complex micelle designed to improve tumor
      accumulation and cancer cell uptake of siRNA following systemic administration.
      Improvement in micelle stability was achieved using two stabilization mechanisms;
      covalent disulfide cross-linking and non-covalent hydrophobic interactions. The
      polymer component was designed to provide disulfide cross-linking and cancer cell
      targeting cyclic RGD peptide ligands, while cholesterol-modified siRNA (Chol
      siRNA) provided additional hydrophobic stabilization to the micelle structure.
      Dynamic light scattering confirmed formation of nano-sized disulfide cross-linked
      micelles (<50 nm in diameter) with a narrow size distribution. Improved stability
      of Chol-siRNA-loaded micelles (Chol-siRNA micelles) was demonstrated by
      resistance to both the dilution in serum-containing medium and counter polyion
      exchange with dextran sulfate, compared to control micelles prepared with Chol
      free siRNA (Chol-free micelles). Improved stability resulted in prolonged blood
      circulation time of Chol-siRNA micelles compared to Chol-free micelles.
      Furthermore, introduction of cRGD ligands onto Chol-siRNA micelles significantly
      facilitated accumulation of siRNA in a subcutaneous cervical cancer model
      following systemic administration. Ultimately, systemically administered
      cRGD/Chol-siRNA micelles exhibited significant gene silencing activity in the
      tumor, presumably due to their active targeting ability combined with the
      enhanced stability through both hydrophobic interactions of cholesterol and
      disulfide cross-linking. 

PMID- 24930856
TI  - Conservative management of vestibular schwannoma.
AB  - INTRODUCTION: Vestibular schwannoma (VS) is a benign, slow-growing tumour
      originating in the 8th cranial nerve. The treatment includes microsurgery,
      stereotactic radiotherapy and conservative management of tumours with periodic
      radiological tests. METHODS: This was a retrospective study of patients with VS
      following conservative management in a tertiary hospital between 1993 and 2013. A
      total of 73 patients were enrolled in our protocol. The mean age at diagnosis was
      59.7 years. The average size was 11.9mm (4-27mm); 58.9% of the tumours were
      intracanalicular and 41.1%, extracanalicular. The mean follow-up period was 35.75
      months. RESULTS: In 87.7% of patients there was no evidence of tumour growth. A
      total of 9 tumours (12.3%) increased in size. The average growth rate was
      0.62mm/year. The percentage of extracanalicular tumours that grew (20%) was
      higher than that of intracanalicular tumours (7%). Seven patients (9.5%)
      experienced significant changes in their symptoms and 6 of these (8.2%)
      experienced a loss of useful hearing. Six patients (8.2%) left follow-up and
      underwent surgery. CONCLUSIONS: Periodic monitoring of vestibular schwannomas
      with magnetic resonance imaging represents an option for management, because most
      small tumours experience little or no growth over time.

PMID- 24930857
TI  - Primary MALT lymphoma of the larynx.

PMID- 24930858
TI  - A novel beta-trefoil lectin from the parasol mushroom (Macrolepiota procera) is
      nematotoxic.
AB  - Lectins are carbohydrate-binding proteins present in all organisms. Some
      cytoplasmic lectins from fruiting bodies of dikaryotic fungi are toxic against a
      variety of parasites and predators. We have isolated, cloned and expressed a
      novel, single domain lectin from Macrolepiota procera, designated MpL.
      Determination of the crystal structure revealed that MpL is a ricin B-like lectin
      with a beta-trefoil fold. Biochemical characterization, site-directed
      mutagenesis, co-crystallization with carbohydrates, isothermal titration
      calorimetry and glycan microarray analyses show that MpL forms dimers with the
      carbohydrate-binding site at the alpha-repeat, with the highest specificity for
      terminal N-acetyllactosamine and other beta-galactosides. A second putative
      carbohydrate-binding site with a low affinity for galactose is present at the
      gamma-repeat. In addition, a novel hydrophobic binding site was detected in MpL
      with specificity for molecules other than carbohydrates. The tissue specific
      distribution of MpL in the stipe and cap tissue of fruiting bodies and its
      toxicity towards the nematode Caenorhabditis elegans indicate a function of MpL
      in protecting fruiting bodies against predators and parasites. DATABASE:
      Nucleotide sequence data have been deposited in the DDBJ/EMBL/GenBank databases
      under accession numbers HQ449738 and HQ449739. Structural data have been
      deposited in the Protein Data Bank under accession codes 4ION, 4IYB, 4IZX and
      4J2S.

PMID- 24930859
TI  - [Children with minor head injury in the emergency department: Is skull
      radiography necessary for children under 2 years?].
AB  - BACKGROUND: Current guidelines on the management of mild head trauma (traumatic
      brain injury/TBI) do not include the presence of a skull fracture in determining
      the risk of intracranial injury. However, in our setting cranial radiography is
      still performed frequently to rule out the presence of skull fracture. OBJECTIVE:
      To estimate the prevalence of clinically-important traumatic brain injuries
      (ciTBI) in children younger than two years of age with mild TBI. PATIENTS AND
      METHODS: Descriptive observational study. All children attended in emergency
      department with mild TBI (Glasgow >=14 points) for a year were included. We
      defined ciTBI as intracranial injuries that caused death or required
      neurosurgery, intubation for more than 24 hours, inotropic drugs or mechanical
      ventilation. RESULTS: The study included 854 children, of which 457 (53.5%) were
      male. The median patient age was 11.0 months (P25-75: 7.5-17.0 months). In 741
      cases (86.8%) the mechanism of TBI was a fall. In 438 cases (51.3%) skull
      radiography was performed. Eleven children (1.3%) had intracranial injury, but
      none met the criteria for ciTBI (estimated prevalence of ciTBI was 0%; CI 95%: 0%
      0.4%). CONCLUSION: Children younger than two years of age with mild TBI have low
      prevalence of ciTBI. Consequently, it is possible to monitor children younger
      than two years with a TBI without performing skull radiography.

PMID- 24930860
TI  - [Malignant peripheral nerve sheath tumour of the infra-orbital nerve].
AB  - A malignant peripheral nerve sheath tumour (MPNST) is an uncommon neoplasm that
      rarely involves the head and neck region. It is even more infrequent for these
      tumours to affect cranial nerves. We report the case of a 53-year-old man who
      presented a MPNST involving the infra-orbital nerve, which extended through the
      orbit and the base of the skull, progressing intracranially. Histological studies
      identified the tumour as an MPNST. Response to radiotherapy was not complete and
      radical surgical resection was impossible, so the patient died 10months later.
      This rare case of MPNST with intracranial involvement illustrates the dismal
      prognosis for patients with these lesions. Prognosis is poor because of the
      difficulty of performing radical surgery with free margins in these locations.

PMID- 24930861
TI  - Cytosolic calreticulin inhibits microwave radiation-induced microvascular
      endothelial cell injury through the integrin-focal adhesion kinase pathway.
AB  - OBJECTIVE: To determine the effects of cytosolic CRT on MR-induced MMEC injury,
      and the underlying mechanism. METHODS: MMECs were randomized into eight groups:
      control, AdCRT (infected with pAdCMV/V5-DEST-CRT adenovirus), stCRT (transfected
      with rCRT-siRNAs), Mock (transfected with scrambled siRNAs), MR (exposed to MR
      for six minutes), AdCRT + MR, stCRT + MR, and Mock + MR. The magnitude of cell
      injury were assessed by Annexin V-PI staining, LDH activity in culture medium,
      MMEC migration ability, ultrastructure and cytoskeletal stability. Subcellular
      colocalization of CRT and ConA or integrin were evaluated by immunocytochemistry.
      The mRNA and protein expression levels of target genes were examined by qRT-PCR
      and western blotting, respectively. RESULTS: MR-induced cytotoxicity was dose
      dependent. Overexpression of cytosolic CRT suppressed MR injury, shown as
      decreased cell apoptosis, reduced LDH activity, enhanced cell migration
      capability, and maintenance of ultrastructure and cytoskeleton integrity.
      Conversely, CRT deficiency aggravated MR-induced injury. Exposure of AdCRT MMECs
      to MR promoted membrane translocation of CRT and the interaction of CRT-integrin
      alpha. Correlation analysis revealed that integrin-alpha expression or FAK
      phosphorylation was positively associated with cytosolic CRT expression.
      CONCLUSIONS: Cytosolic CRT inhibits MR-induced MMEC injury through activation of
      the integrin-FAK pathway.

PMID- 24930862
TI  - [Enteropathy associated with chronic use of olmesartan].

PMID- 24930863
TI  - Editorial Comment from Dr Mirone et al. to Resiniferatoxin for treatment of
      lifelong premature ejaculation: a preliminary study.

PMID- 24930864
TI  - Elucidating the impact of temperature variability and extremes on cereal
      croplands through remote sensing.
AB  - Remote sensing-derived wheat crop yield-climate models were developed to
      highlight the impact of temperature variation during thermo-sensitive periods
      (anthesis and grain-filling; TSP) of wheat crop development. Specific questions
      addressed are: can the impact of temperature variation occurring during the TSP
      on wheat crop yield be detected using remote sensing data and what is the impact?
      Do crop critical temperature thresholds during TSP exist in real world cropping
      landscapes? These questions are tested in one of the world's major wheat
      breadbaskets of Punjab and Haryana, north-west India. Warming average minimum
      temperatures during the TSP had a greater negative impact on wheat crop yield
      than warming maximum temperatures. Warming minimum and maximum temperatures
      during the TSP explain a greater amount of variation in wheat crop yield than
      average growing season temperature. In complex real world cereal croplands there
      was a variable yield response to critical temperature threshold exceedance,
      specifically a more pronounced negative impact on wheat yield with increased
      warming events above 35  degrees C. The negative impact of warming increases with
      a later start-of-season suggesting earlier sowing can reduce wheat crop exposure
      harmful temperatures. However, even earlier sown wheat experienced temperature
      induced yield losses, which, when viewed in the context of projected warming up
      to 2100 indicates adaptive responses should focus on increasing wheat tolerance
      to heat. This study shows it is possible to capture the impacts of temperature
      variation during the TSP on wheat crop yield in real world cropping landscapes
      using remote sensing data; this has important implications for monitoring the
      impact of climate change, variation and heat extremes on wheat croplands. 

PMID- 24930865
TI  - A dynamic synchrotron X-ray imaging study of effective temperature in a vibrated
      granular medium.
AB  - We present a dynamic synchrotron X-ray imaging study of the effective temperature
      Teff in a vibrated granular medium. By tracking the directed motion and the
      fluctuation dynamics of the tracers inside, we obtained Teff of the system using
      the Einstein relationship. We found that as the system unjams with increasing
      vibration intensities Gamma, the structural relaxation time tau increases
      substantially which can be fitted by an Arrhenius law using Teff. And the
      characteristic energy scale of structural relaxation yielded by the Arrhenius
      fitting is E = 0.20 +/- 0.02pd(3), where p is the pressure and d is the
      background particle diameter, which is consistent with those from hard sphere
      simulations in which the structural relaxation happens via the opening up of free
      volume against pressure. 

PMID- 24930866
TI  - Nodular lymphoid hyperplasia of the colon in a vervet monkey (Cholorocebous
      aethiops).
AB  - BACKGROUND: Diffuse nodular lymphoid hyperplasia (DNLH) of gastrointestinal tract
      is regarded as a very rare disease in the adult population. It is characterized
      by presence of diffuse detectable small polypoid masses distributed in the small
      intestine, colon, or both. METHODS: A 6-year-old male in captivity suddenly died,
      due to myocardial infarction. During routine necropsy procedure, incidentally,
      numerous tan, sessile polyps, up to 0.2 cm were noticed in all segments of the
      colon. RESULTS: Histopathological and immunohistochemical examination revealed
      polypoid masses as nodular lymphoid hyperplasia (NLH), comparable with DNLH of
      the colon in human. CONCLUSIONS: In this article, the author has tried to
      introduce some immunosuppresive (e.g., simian retrovirus type D (SRV), simian
      immunodeficiency virus (SIV)) and opportunistic viruses (e.g., lymphocryptovirus,
      gamma-herpesvirus, adenovirus), as well as, primary and opportunistic bacteria
      (e.g., Yersinia psedotuberculosis, and Helicobacter spp.) that may trigger benign
      reactive process, lymphoid hyperplasia, in non-human primates (NHPs) in
      captivity.

PMID- 24930867
TI  - Fate of Clostridium difficile during wastewater treatment and incidence in
      Southern Ontario watersheds.
AB  - AIMS: To investigate the prevalence of Clostridium difficile encountered during
      sewage treatment and in water sources into which treated effluent was directly or
      indirectly discharged. METHODS AND RESULTS: Samples from wastewater treatment
      plants (WWTPs) and rivers were collected and then enriched for Cl. difficile.
      Each of the isolates was subjected to toxinotyping and DNA typing using
      ribotyping, in addition to pulse-field gel electrophoresis. Cl. difficile was
      isolated from 92% (108/117) of the raw sludge and 96% (106/110) of the anaerobic
      digested sludge samples from two Ontario WWTPs. The pathogen was recovered from
      73% (43/59) of dewatered biosolids and effluent discharge, in addition to river
      sediments 39% (25/64). Ribotype 078 (commonly associated with Community Acquired
      infections) was recovered from raw sewage (19%; 21/108), digested sludge (8%;
      8/106), biosolids (35%; 15/43) and river sediments (60%; 15/25). CONCLUSIONS:
      Clostridium difficile is commonly encountered in raw sewage and survives the
      wastewater treatment process. The pathogen can then be disseminated into the
      wider environment via effluent and land application of biosolids. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The study has illustrated the wide distribution of
      toxigenic Cl. difficile in WWTPs and river sediments although the clinical
      significance still requires to be elucidated.

PMID- 24930868
TI  - Effects of conservatively treated diseased cementum with or without EMD on in
      vitro cementoblast differentiation and in vivo cementum-like tissue formation of
      human periodontal ligament cells.
AB  - OBJECTIVES: The present study aimed to evaluate the effects of conservatively
      treated diseased cementum on in vitro cementoblast differentiation and in vivo
      cementum-like tissue formation of human periodontal ligament cells (hPDLCs), and
      observe differential effects of enamel matrix derivative (EMD) on in vivo
      cementum formation by hPDLCs. MATERIALS AND METHODS: Forty-eight cementum slices
      and 48 dentin slices were prepared from periodontitis compromised teeth, and
      hPDLCs were inoculated on to all root slices. Twenty-four co-cultured root slices
      of each group were used for mRNA expression of cementum attachment protein and
      CEMP1. With application of EMD, 24 co-cultured root slices (divided into groups
      C, D, C+E, D+E) were transplanted subcutaneously into nude mice. All root
      fragments were reviewed by histological analysis and immunohistochemical staining
      for bone sialoprotein. RESULTS: mRNA expressions of cementum attachment protein
      and cementum protein - 1 from hPDLCs on cementum slices were statistically higher
      than those of dentin slices. Seven specimens of group C and 10 specimens of group
      C+E revealed a layer of cementum-like tissue (NFC) on surfaces of pre-existing
      cementum. NFC was thicker in group C+E than in group C. All NFCs were positively
      stained for bone sialoprotein, however, there was no NFC formation on dentin
      slices. CONCLUSION: Conservatively treated diseased cementum promoted in vitro
      cementoblast differentiation and in vivo cementum-like tissue formation by
      hPDLCs, and the in vivo effect was enhanced by the presence of EMD.

PMID- 24930869
TI  - A 3 years retrospective study of survival for zirconia-based single crowns
      fabricated from intraoral digital impressions.
AB  - OBJECTIVE: To evaluate the clinical performance of glass-ceramic/zirconia crowns
      fabricated using intraoral digital impressions - a retrospective study with a
      three-year follow-up. METHODS: 70 consecutive patients with a total of 86 glass
      ceramic/zirconia crowns were treated by a single clinician using standardized
      clinical and laboratory protocols. A complete digital workflow was adopted for
      the purpose except for the veneering procedure for the glass-ceramic crowns.
      Occlusal adjustments were made before the ceramic glazing procedure. Before
      cementation, all abutments where carefully cleaned with a 70% alcoholic solution
      and air dried. Cementation was performed using dual-curing, self-adhesive resin
      cement. Patients were re-examined after 12, 24 and 36 months, to assess crown
      chipping/fractures. RESULTS: After the three-year follow-up, none of the zirconia
      based restoration was lost ("apparent" survival rate 100%) otherwise, the
      chipping rate of the veneering material increased from 9.3% after 12 months, to
      14% after 24 months to 30.2% after 36 months. As a consequence, the "real"
      success rate after 3 years was 69.8%. CONCLUSIONS: After 3 years the success rate
      of zirconia-based crowns was 69.8%, while the incidence of the chipping was
      30.2%. Assuming an exponential increase in chipping rate between 12 and 36 months
      it can be argued that, among others, the fatigue-mechanism could be advocated as
      the main factor for the failure of glass-ceramic veneered zirconia especially
      after 24 months.

PMID- 24930870
TI  - A new "silver-bullet" to treat caries in children--nano silver fluoride: a
      randomised clinical trial.
AB  - BACKGROUND: Untreated dental caries in children remains a public health challenge
      in poor communities. OBJECTIVES: This prospective controlled clinical trial
      investigated the effectiveness of a new anti-caries agent, Nano Silver Fluoride
      (NSF), applied once a year to arrest caries in children. METHODS: One hundred
      thirty decayed primary teeth were randomly divided into two groups: NSF as the
      experimental agent and water as the control group. Teeth were clinically
      diagnosed and treated by one masked examiner and followed up at seven days and
      five and 12 months by another calibrated examiner who was blinded to the type of
      treatment. The criteria of the ICDAS II were followed to determine the activity
      of lesion and the diagnosis of caries. The Pearson's chi-square test was used to
      compare the groups during different follow-up exams. RESULTS: At seven days, 81%
      of teeth in the NSF group exhibited arrested caries, whereas in controls, no
      teeth had arrested decay (p<0.001) [PF, prevented fraction=81%]. After five
      months, the NSF group had 72.7% with arrested decay, and the control group had
      27.4% (p<0.001) [PF=62.5%]. At 12 months, 66.7% of the lesions treated with NSF
      were still arrested, while the control group had 34.7% remaining arrested
      (p=0.003) [PF=50%]. The number need to treat (NNT) at five months was two, and at
      12 months, the number was three. CLINICAL SIGNIFICANCE: The NSF formulation is
      effective to arrest active dentine caries and not stain teeth. CONCLUSIONS: NSF
      was demonstrated to be effective in arresting caries in children in poor
      communities.

PMID- 24930873
TI  - Randomized controlled trials in dentistry: common pitfalls and how to avoid them.
AB  - OBJECTIVE: Clinical trials are used to appraise the effectiveness of clinical
      interventions throughout medicine and dentistry. Randomized controlled trials
      (RCTs) are established as the optimal primary design and are published with
      increasing frequency within the biomedical sciences, including dentistry. This
      review outlines common pitfalls associated with the conduct of randomized
      controlled trials in dentistry. METHODS: Common failings in RCT design leading to
      various types of bias including selection, performance, detection and attrition
      bias are discussed in this review. Moreover, methods of minimizing and
      eliminating bias are presented to ensure that maximal benefit is derived from
      RCTs within dentistry. CONCLUSIONS: Well-designed RCTs have both upstream and
      downstream uses acting as a template for development and populating systematic
      reviews to permit more precise estimates of treatment efficacy and effectiveness.
      However, there is increasing awareness of waste in clinical research, whereby
      resource-intensive studies fail to provide a commensurate level of scientific
      evidence. Waste may stem either from inappropriate design or from inadequate
      reporting of RCTs; the importance of robust conduct of RCTs within dentistry is
      clear. CLINICAL SIGNIFICANCE: Optimal reporting of randomized controlled trials
      within dentistry is necessary to ensure that trials are reliable and valid.
      Common shortcomings leading to important forms or bias are discussed and
      approaches to minimizing these issues are outlined.

PMID- 24930872
TI  - Layer-by-layer self-assembly of minocycline-loaded chitosan/alginate multilayer
      on titanium substrates to inhibit biofilm formation.
AB  - OBJECTIVES: Bacteria adhesion and subsequent biofilm formation are primary causes
      of implant associated infection. The biofilm makes the bacteria highly resistant
      to the host defense and antimicrobial treatment. Antibacterial coatings on the
      surface of titanium implant can prevent biofilm formation effectively, but it is
      still a challenge to accomplish relatively long lasting antibacterial effects
      before wound healing or formation of biological seal. The purpose of our work was
      to construct antibacterial multilayer coatings loaded with minocycline on surface
      of Ti substrates using chitosan and alginate based on layer-by-layer (LbL) self
      assembly technique. METHODS: In this study, the surfaces of Ti substrates were
      first hydroxylated and then treated with 3-aminopropyltriethoxysilane (ATPES) to
      obtain amino-functionalized Ti substrates. Next, the precursor layer of chitosan
      was covalently conjugated to amino-functionalized Ti substrates. The following
      alternately coating alginate loaded with minocycline and chitosan onto the
      precursor layer of chitosan was carried out via LbL self-assembly technique to
      construct the multilayer coatings on Ti substrates. RESULTS: The multilayer
      coatings loaded more minocycline and improved sustainability of minocycline
      release to kill planktonic and adherent bacteria. Moreover, surface charge and
      hydrophilicity of the coatings and antibacterial ability of chitosan itself also
      played roles in the antibacterial performance, which can keep the antibacterial
      ability of the multilayer coatings after minocycline release ceases. CONCLUSIONS:
      In conclusion, LbL self-assembly method provides a promising strategy to
      fabricate long-term antibacterial surfaces, which is especially effective in
      preventing implant associated infections in the early stage. CLINICAL
      SIGNIFICANCE: Loading minocycline on the surface of implants based on LbL self
      assembly strategy can endow implants with sustained antibacterial property. This
      can inhabit the immediate colonization of bacteria onto the surface of implants
      in the process of dental implant surgery, and thereby prevents and reduces the
      occurrence of periimplantitis.

PMID- 24930871
TI  - One-pot synthesis of antibacterial monomers with dual biocidal modes.
AB  - OBJECTIVES: The present study reported a method for preparing a blend of
      antibacterial quaternary ammonium silanes and quaternary ammonium methacryloxy
      silane (QAMS) based on the sol-gel reaction between dimethyldiethoxy silane and
      two trialkoxysilanes, one with an antibacterial quaternary ammonium functionality
      and the other with a methacryloxy functionality. METHODS: Reaction products of
      the sol-gel reaction were characterised by direct infusion mass spectrometry,
      FTIR and proton, carbon and silicon NMR. This blend of monomers was incorporated
      into an experimental universal adhesive for evaluation of antimicrobial activity
      against Streptococcus mutans biofilms, microtensile bond strength and
      cytotoxicty. Retention of quaternary ammonium species on polymerised adhesive,
      leaching of these species from the adhesive and the ability of resin-dentine
      interfaces to inhibit S. mutans biofilms were evaluated over a 3-month water
      ageing period. RESULTS: The antibacterial adhesive version killed bacteria in S.
      mutans biofilms not only through the release of non-copolymerisable quaternary
      ammonium silane species (release-killing), but also via immobilised quaternary
      ammonium methacryloxy silane that are copolymerised with adhesive resin
      comonomers (contact-killing). Contact-killing was retained after water-ageing.
      The QAMS-containing universal adhesive has similar tensile bond strength as the
      control and two commercially available universal adhesives, when it was used for
      bonding to dentine in the etch-and-rinse mode and self-etching mode.
      Incorporation of the antimicrobial quaternary ammonium species blend did not
      adversely affect the cytotoxicity of the universal adhesive formulation.
      CONCLUSIONS: Instead of using quaternary ammonium dimethacrylates and nanosilver,
      an alternative bimodal antimicrobial strategy for formulating antimicrobial
      universal dentine adhesives is achieved using the one-pot sol-gel synthesis
      scheme. CLINICAL SIGNIFICANCE: The QAMS containing universal dentine adhesives
      with dual antimicrobial activity is a promising material aimed at preventing
      second caries and prolonging the longevity of resin composite restorations.

PMID- 24930874
TI  - Involvement of reactive oxygen species in stimuli-induced shedding of heparin
      binding epidermal growth factor-like growth factor.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a critical
      growth factor for a number of physiological and pathological processes, such as
      wound healing, atherosclerosis and cancer proliferation. HB-EGF is synthesized as
      a membrane form (proHB-EGF), and is shedded at the cell surface to yield soluble
      HB-EGF, resulting in making it active. In this study, the involvement of reactive
      oxygen species (ROS) in stimuli-induced shedding of HB-EGF was investigated using
      monkey kidney Vero cells overexpressing HB-EGF (Vero-H cells). 12-O
      tetradecanoylphorbol-13-acetate (TPA), lysophosphatidic acid (LPA) as a ligand
      for seventransmembrane G protein coupled receptors (GPCR) and sorbitol as stress
      induced shedding of HB-EGF mediated protein kinase C (PKC)-delta, mitogen
      activated protein kinase (MAPK) and p38MAPK, respectively. These stimuli-induced
      sheddings of HB-EGF were inhibited by N-acetyl-L-cysteine (NAC), suggesting the
      involvement of ROS. As specific inhibitors of these protein kinases inhibited the
      shedding of HB-EGF, these signaling pathways seem to be independent,
      respectively. In contrast, gamma-ray irradiation did not induce shedding although
      it did increase intracellular ROS levels. Taken together, these results suggest
      that the synergistic generation of ROS and the activation of protein kinase are
      required to promote stimuli-induced shedding of HB-EGF. 

PMID- 24930875
TI  - Lipoblast: morphologic features and diagnostic value.
AB  - Lipoblasts are conceptually a precursor or immature form of adipocytes and
      histologically defined as lipid-containing, mono- or multivacuolated cells
      possessing hyperchromatic, indented or often scalloped nuclei. They are
      essentially identified in neoplastic conditions and assumed to recapitulate, to
      some extent, the differentiation process of normal fat (adipogenesis) like their
      potential normal counterpart, preadipocyte or preadipose cell. Traditionally,
      great emphasis has been placed on the identification of lipoblasts in diagnostic
      pathology, particularly of liposarcoma. However, it is not always an easy task
      for pathologists because of a variety of histological mimics such as Lochkern
      cells, brown fat cells and pseudolipoblasts. Currently, lipoblasts are not a
      prerequisite for the diagnosis of liposarcoma partly because of some benign
      tumors harboring lipoblasts or lipoblast-like cells such as spindle
      cell/pleomorphic lipoma and chondroid lipoma, although their presence is still
      crucial for proper diagnosis. This review summarizes the clinicopathologic
      features of lipoblasts, their histological mimics and representative benign
      tumors carrying lipoblasts to facilitate routine pathology practice and to avoid
      erroneous diagnosis of liposarcoma. 

PMID- 24930876
TI  - A case of idiopathic gastroesophageal submucosal hematoma and its disappearance
      observed by endoscopy.
AB  - A 74-year-old man was hospitalized due to hematemesis. Upper gastrointestinal
      endoscopy revealed a very large and dark red mass in the cardiac region of the
      stomach that extended from the upper esophagus. A biopsy specimen showed
      hemorrhagic tissue and no malignant cells. The tumor-like region ulcerated at 5
      days after the administration of intravenous lansoprazole at a dose of 30 mg
      twice a day and resolved with scar formation at 2 months after a change to oral
      rabeprazole at a dose of 10 mg/day.We diagnosed the patient with gastroesophageal
      submucosal hematoma. Gastroesophageal submucosal hematoma is a rare complication.
      In this case, we could follow the process of its disappearance by endoscopy. 

PMID- 24930877
TI  - Limbic encephalitis associated with anti-voltage-gated potassium channel complex
      antibodies as a cause of adult-onset mesial temporal lobe epilepsy.
AB  - Recently, some reports have indicated that limbic encephalitis associated with
      anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of
      adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman
      who had her first epileptic seizure at the age of 50 years old. Examination by 3
      Tesla brain MRI revealed left hippocampal high signal intensity and swelling on
      fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months
      after her first seizure. The patient received intravenous methylprednisolone and
      carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left
      hippocampal abnormalities. Thereafter, she had no seizures, however, three years
      after her first seizure, EEG revealed a seizure pattern in the left temporal
      region. Brain MRI revealed left hippocampal high signal intensity and brain
      fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her
      serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone
      therapy was reinitiated. Two months later, her hippocampal abnormalities had
      improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of
      the epileptic seizures was also observed. This MTLE in the middle age was
      considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of
      unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab,
      which responds well to immunotherapy, should be considered in the differential
      diagnosis. 

PMID- 24930878
TI  - A survey on bacterial contamination of lavage water in electric warm-water lavage
      toilet seats and of the gluteal cleft after lavage.
AB  - Electric warm-water lavage toilet seats are in wide use as an appliance
      beneficial for the maintenance of hygiene and the prophylaxis and improvement of
      conditions such as constipation and hemorrhoids. In this study, we surveyed the
      bacterial content in the lavage water of warm-water lavage toilet seats, and
      fecal bacterial contamination of the gluteal and genital regions due to droplet
      infection from post-defecation lavage, to examine the problems inherent to the
      use of such lavage units. The presence of viable bacteria in lavage water was
      confirmed in this survey. Viable bacterial counts in lavage water were 3-times
      higher in household units compared to units in public facilities, suggesting a
      correlation with the replenishment of lavage tank water with fresh water
      containing residual free chlorine. 

PMID- 24930879
TI  - [An approach to bone and cartilage repair of rheumatoid arthritis by mesenchymal
      stem cells].
AB  - Rheumatoid arthritis (RA) is an autoimmune disease represented by chronic
      inflammation and following structural damage at the articular joints. Progression
      of the disease causes disability and subsequent early retirement or a care
      requiring condition. Although new agents have the potential of complete
      inhibition of joint damage, there is still a considerable number of patients with
      progressed joint damage who couldn't receive the benefits of these agents because
      of the long duration of their disease or uncontrollable disease activity. Thus, a
      new treatment tool for RA aiming at joint repair is necessary. Mesenchymal stem
      cells (MSCs) are known to build bone and cartilage, and also have
      immunosuppressive ability. We have considered MSCs as a new treatment tool of RA,
      and have reported that MSCs suppress osteoclastogenesis. More recently, we also
      reported that inflammation induces osteogenesis and suppresses the chondrogenesis
      of MSCs. An investigation of a new delivery system of MSCs to the target lesion
      is now ongoing. The data from this investigation suggest that MSCs can be a new
      application in the treatment of RA. 

PMID- 24930880
TI  - [Two cases of acute respiratory distress syndrome related to zinc fumes and zinc
      dust inhalation].
AB  - Two cases of acute respiratory distress syndrome related to zinc fume inhalation
      and zinc powder inhalation are presented. Case 1 demonstrated acute respiratory
      symptoms during the work of distortion correction of iron boards, coated with a
      rust preventative including rich zinc using an acetylene gas burner. Case 2
      occurred after the work of applying a rust preventative that included zinc
      powder, mainly using an airless compressor. Since both were working in a
      boathouse, without using protective equipment, the possible causes of Case 1 and
      2 were inhalation exposure to zinc fumes and zinc powder, respectively. The two
      patients showed similar clinical courses, including favorable treatment outcomes,
      mimicking acute respiratory failure complicated by a metal fume fever. 

PMID- 24930881
TI  - [Trial of a rapid measurement method by absorption photometer for the
      determination of the number of bacteria in the air].
AB  - A quick method to measure the number and the concentration of airborne bacteria
      was examined by combining bacteria staining with a crystal violet solution and
      absorptiometry. The suspension of the bacteria isolated from the environment was
      adjusted to 3.0 * 10(8) colony forming units (CFU) / ml in E. coli equivalent,
      and a 10-fold dilution series was created. After centrifugation of each bacterial
      suspension, the supernatant was removed and the bacteria were stained by adding a
      crystal violet solution. The sample was centrifuged again, and the supernatant
      was collected and named the unabsorbed sample. The residual bacteria were washed
      two times, and ethanol was added to the stained cells. The recovered solution
      collected by centrifugation of the cells was named the recovered sample.The
      chemicals in the samples were examined by high performance liquid chromatography,
      but no peak could be observed without the staining material. Absorption
      spectrophotometry showed that the determination limit of bacteria in the
      unabsorbed samples was 3.0 * 10(7) CFU / ml in E. coli equivalent and that in the
      recovered samples was 3.0 * 10(8) CFU / ml, indicating that the unabsorbed sample
      had a lower determination limit. 

PMID- 24930882
TI  - Immune cell function assay in pediatric heart transplant recipients.
AB  - The ImmuKnow ICFA reports ex vivo CD4 lymphocyte activation to quantify
      immunosuppression. Limited organ and age-specific data exist for pediatric heart
      transplant recipients. We sought to examine their normative values and ICFA's
      association with rejection/infection. A total of 380 ICFAs from 58 heart
      transplant recipients (6.5/recipient) were studied retrospectively. The median
      age at the time of their first ICFA was 5.3 yr (IQR 2.4-12.1 yr). ICFA levels
      during immunologic stability (n = 311) were a median of 305 (IQR: 172-483) and
      mean of 353 (s.d. +/- 224) ng ATP/mL. ICFA levels trended lower with advancing
      age. ICFA levels during immunologic stability increased over time from transplant
      after the first six months but were not correlated with calcineurin inhibitor
      levels or the type used. There is no association between ICFA values during
      stability and rejection (median 368 ATP ng/mL; IQR 153-527) or infection (median
      293 ATP ng/mL; IQR 198-432). In contrast to the manufacturer's suggested ranges,
      the immunologic stable ranges in pediatric cardiac recipients were very
      different. ICFA values during immunologic stability are related to time from
      transplant in pediatric heart recipients. ICFA's ability to discriminate
      rejection or infection from immunologic stability was not demonstrated.

PMID- 24930883
TI  - Carotid adventitial vasa vasorum and intima-media thickness in a primary
      prevention population.
AB  - BACKGROUND: Vasa vasorum (VV) vessels are critical in the genesis of
      atherosclerosis. Therefore, we assessed measures of carotid VV, intima-media
      thickness (CIMT), and patient risk factors in a primary prevention population.
      METHODS: We used multivariable linear models to evaluate the relationship between
      baseline covariates and a measure of carotid VV (VV ratio) and CIMT among 324
      diabetics and 141 nondiabetics. RESULTS: Median CIMT (in mm) and VV ratio among
      nondiabetics were 0.82 +/- 0.22 and 0.80 +/- 0.19, respectively, and 1.06 +/-
      0.19 and 1.21 +/- 0.26 among diabetics (P < 0.0001). Diabetes was associated with
      36% (95% CI: 24.3-48.0, P < 0.001) higher VV ratio whereas a unit change in BMI
      was associated with ~1% (95% CI: 0.5-1.4, P < 0.001) change in VV ratio. A 10
      year increase in age was associated with 4% (95% CI: 1-7, P = 0.005) higher CIMT.
      Each 10 mmHg increase in mean systolic blood pressure was associated with 2% (95%
      CI: 1-4, P = 0.003) higher CIMT whereas diabetes conferred 31% (95% CI: 19.1
      42.1, P < 0.001) higher CIMT. Female sex was associated with a 9% (95% CI: -12.9
      to -4.1, P < 0.001) lower CIMT. Low density lipoprotein (LDL) cholesterol, blood
      pressure, and CIMT were not significantly associated with VV ratio. CONCLUSION:
      In this cohort of patients with low CIMT, VV ratio, and CIMT were distinctly
      unrelated, but each independently associated with diabetes. VV ratio and CIMT
      relationships warrant further investigation in large-scale studies and across a
      spectrum of atherosclerostic states.

PMID- 24930884
TI  - A linear diffusion model for ion current across blocking grain boundaries in
      oxygen-ion and proton conductors.
AB  - We demonstrate the applicability of the linear diffusion model recently proposed
      for the current-voltage, Igb-Ugb, characteristics of blocking grain boundaries in
      solid electrolytes to various oxygen-ion and proton conductors: the model
      precisely reproduces the Igb-Ugb characteristics of La-, Sm-, Gd-, and Y-doped
      ceria as well as Y-doped barium zirconate to provide accurate explanations to the
      "power law" behavior of the Igb-Ugb relationship, i.e. Igb ? Ugb(n),
      experimentally observed. The model also predicts that the grain-boundary
      potential, Psigb, in doped ceria weakly depends on temperature, if the trapped
      charge remains constant, and that the value of Psigb can be determined from the
      value of the power n. Furthermore, the model provides a plausible explanation for
      the increase in the Psigb with temperature observed for the proton conductor in
      which the concentration of the charge carrier decreases with temperature. Hence,
      it is evident that the linear diffusion model is robust and applicable to grain
      boundaries in a large variety of practically important solid electrolytes. 

PMID- 24930885
TI  - Preclinical evaluation of efficacy and stability of docetaxel micelle
      encapsulated by a tripodal cyclotriphosphazene amphiphile.
AB  - Docetaxel formulated by micelle-encapsulation using a tripodal
      cyclotriphosphazene amphiphile [NP(MPEG750)(GlyPheLeu)2Et]3 (CP750) was named
      "Phostaxel" and compared in efficacy and stability with Taxotere((r)) formulated
      using the surfactant polysorbate 80, which is currently in clinical use.
      Phostaxel has always shown better efficacy than Taxotere((r)) in various
      xenograft trials at the same dosage and administration schedule against the tumor
      cell lines tested. The better efficacy of Phostaxel could be explained based on
      the difference in pharmacokinetic and biodistribution profiles of Phostaxel and
      Taxotere((r)). Phostaxel exhibited significantly slower clearance rate and larger
      AUClast value compared with Taxotere((r)). Phostaxel has also shown higher DTX
      distribution in tumor than Taxotere((r)). In addition, Phostaxel displayed better
      solution stability compared with Taxotere((r)) both in distilled water and in
      saline solution at room and refrigerator temperatures. 

PMID- 24930886
TI  - KPNA2 is overexpressed in human and mouse endometrial cancers and promotes
      cellular proliferation.
AB  - Endometrial cancer is the most frequently occurring malignancy of the female
      genital tract in Western countries. Although in many cases surgically curable,
      about 30% of the tumours represent an aggressive and untreatable disease. In an
      attempt to establish a reliable prognostic marker for endometrial carcinomas
      disregarding their histological diversity, we investigated the expression of
      KPNA2, a mediator of nucleocytoplasmic transport, and other cell proliferation
      associated proteins and their correlation with cancer progression. We analysed
      patient tissue microarrays (TMAs) assembled from 527 endometrial cancer tissue
      specimens and uterus samples from a Trp53 knockout mouse model of endometrial
      cancer. Our data show that KPNA2 expression was significantly up-regulated in
      human endometrial carcinomas and associated with higher tumour grade (p = 0.026),
      higher FIGO stage (p = 0.027), p53 overexpression (p < 0.001), activation of the
      PI3K/AKT pathway, and epithelial-mesenchymal transition. Increased nuclear KPNA2
      immunoreactivity was identified as a novel predictor of overall survival,
      independent of well-established prognostic factors in Cox regression analyses
      (hazard ratio 1.7, 95% CI 1.13-2.56, p = 0.01). No significant association
      between KPNA2 expression and endometrial cancer subtype was detected. In the
      mouse model, KPNA2 showed increased expression levels from precancerous (EmgD,
      EIC) to far-advanced invasive lesions. We further investigated the cell
      proliferation capacity after siRNA-mediated KPNA2 knockdown in the human
      endometrial cancer cell line MFE-296. KPNA2 silencing led to decreased
      proliferation of the cancer cells, suggesting interplay of the protein with the
      cell cycle. Taken together, increased expression of KPNA2 is an independent
      prognostic marker for poor survival. The mechanism of enhanced nucleocytoplasmic
      transport by KPNA2 overexpression seems a common event in aggressive cancers
      since we have shown a significant correlation of KPNA2 expression and tumour
      aggressiveness in a large variety of other solid tumour entities. Introducing
      KPNA2 immunohistochemistry in routine diagnostics may allow for the
      identification of patients who need more aggressive treatment regimens.

PMID- 24930887
TI  - HGF/MET-directed therapeutics in gastroesophageal cancer: a review of clinical
      and biomarker development.
AB  - Aberrant activation of the HGF/MET signaling axis has been strongly implicated in
      the malignant transformation and progression of gastroesophageal cancer (GEC).
      MET receptor overexpression in tumor samples from GEC patients has been
      consistently correlated with an aggressive metastatic phenotype and poor
      prognosis. In preclinical GEC models, abrogation of HGF/MET signaling has been
      shown to induce tumor regression as well as inhibition of metastatic
      dissemination. Promising clinical results in patient subsets in which MET is
      overexpressed have spurned several randomized studies of HGF/MET-directed agents,
      including two pivotal global Phase III trials. Available data highlight the need
      for predictive biomarkers in order to select patients most likely to benefit from
      HGF/MET inhibition. In this review, we discuss the current knowledge of
      mechanisms of MET activation in GEC, the current status of the clinical
      evaluation of MET-targeted therapies in GEC, characteristics of ongoing
      randomized GEC trials and the associated efforts to identify and validate
      biomarkers. We also discuss the considerations and challenges for HGF/MET
      inhibitor drug development in the GEC setting. 

PMID- 24930888
TI  - The hypocretin/orexin system mediates the extinction of fear memories.
AB  - Anxiety disorders are often associated with an inability to extinguish learned
      fear responses. The hypocretin/orexin system is involved in the regulation of
      emotional states and could also participate in the consolidation and extinction
      of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2
      antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1
      knockout mice, we investigated the role of the hypocretin system in cue- and
      context-dependent fear conditioning and extinction. Hypocretins were crucial for
      the consolidation of fear conditioning, and this effect was mainly observed in
      memories with a high emotional component. Notably, after the acquisition of fear
      memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas
      hypocretin-1 administration impaired this extinction process. The extinction
      facilitating effects of the hypocretin receptor-1 antagonist SB334867 were
      associated with increased expression of cFos in the basolateral amygdala and the
      infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal
      cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction.
      These results reveal a key role for hypocretins in the extinction of aversive
      memories and suggest that hypocretin receptor-1 blockade could represent a novel
      therapeutic target for the treatment of diseases associated with inappropriate
      retention of fear, such as post-traumatic stress disorder and phobias. 

PMID- 24930889
TI  - Extending the viability of acute brain slices.
AB  - The lifespan of an acute brain slice is approximately 6-12 hours, limiting
      potential experimentation time. We have designed a new recovery incubation system
      capable of extending their lifespan to more than 36 hours. This system controls
      the temperature of the incubated artificial cerebral spinal fluid (aCSF) while
      continuously passing the fluid through a UVC filtration system and simultaneously
      monitoring temperature and pH. The combination of controlled temperature and UVC
      filtering maintains bacteria levels in the lag phase and leads to the dramatic
      extension of the brain slice lifespan. Brain slice viability was validated
      through electrophysiological recordings as well as live/dead cell assays. This
      system benefits researchers by monitoring incubation conditions and standardizing
      this artificial environment. It further provides viable tissue for two
      experimental days, reducing the time spent preparing brain slices and the number
      of animals required for research.

PMID- 24930891
TI  - Invadopodia, regulation, and assembly in cancer cell invasion.
AB  - The occurrence of invadopodia has been, since its characterization, a hallmark of
      cancerous cell invasion and metastasis. These structures are now the subject of a
      controversy concerning their cellular function, molecular regulation, and
      assembly. The terms invadopodia and podosomes have been used interchangeably
      since their discovery back in 1980. Since then, these phenotypes are now more
      established and accepted by the scientific community as vital structures for 3D
      cancer cell motility. Many characteristics relating to invadopodia and podosomes
      have been elucidated, which might prove these structures as good targets for
      metastasis treatment. In this review, we briefly review the actin reorganization
      process needed in most types of cancer cell motility. We also review the
      important characteristics of invadopodia, including molecular components,
      assembly, markers, and the signaling pathways, providing a comprehensive model
      for invadopodia regulation.

PMID- 24930890
TI  - WNT signaling and distant metastasis in colon cancer through transcriptional
      activity of nuclear beta-Catenin depend on active PI3K signaling.
AB  - We determined whether active PI3K signaling together with nuclear accumulation of
      beta-Catenin is necessary to fully activate canonical WNT signaling and examined
      the association of both signaling pathways with colon cancer progression. Using
      reporter gene assays we examined the activation of beta-Catenin mediated
      transcription upon PI3K inhibition with or without beta-Catenin nuclear
      accumulation. Ectopically induced as well as constitutively active WNT signaling
      strictly required PI3K activity whereas PI3K inhibition had no effect on beta
      Catenin subcellular localization but impaired beta-Catenin binding to WNT target
      gene promoters and decreased WNT target gene expression. Transcriptional activity
      of nuclear beta-Catenin depended on active PI3K signaling as nuclear accumulation
      of beta-Catenin failed to induce WNT reporter gene transcription upon PI3K
      inhibition. PI3K dependend transcriptional transactivation of beta-Catenin relies
      on events beyond phosphorylation at the AKT target site serine 552, as S552D
      phosphomimetic beta-Catenin mutants were unable to restore WNT signaling when
      inhibiting PI3K. To study the prognostic value of PI3K pathway activation
      (activating PIK3CA mutations or loss of PTEN expression) and nuclear beta-Catenin
      expression, both variables were determined in 55 matched pairs of primary right
      sided colon cancer cases with or without distant metastasis. Activating mutations
      in the PIK3CA gene or loss of PTEN expression did not correlate with distant
      metastasis while high nuclear beta-Catenin expression combined with activation of
      the PI3K pathway identified cases in which distant metastasis had occurred.
      Activation of the PI3K pathway was not associated with nuclear beta-Catenin
      expression. We conclude that the transcriptional activity of nuclear beta-Catenin
      depends on PI3K activity. However, PI3K on its own does not affect beta-Catenin
      subcellular localization. Both factors synergize for full WNT signaling activity
      and are associated with distant metastasis in colon cancer. Thus, the detection
      of high nuclear beta-Catenin expression and simultaneous PI3K pathway activation
      identifies colon cancer patients with a high risk for distant metastasis. 

PMID- 24930892
TI  - Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor
      and ameloblastoma.
AB  - BACKGROUND: Sonic hedgehog (SHH) pathway activation has been identified as a key
      factor in the development of many types of tumors, including odontogenic tumors.
      Our study examined the expression of genes in the SHH pathway to characterize
      their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and
      ameloblastomas (AB). METHODS: We quantified the expression of SHH, SMO, PTCH1,
      SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three
      non-neoplastic oral mucosa (NNM). We also measured the expression of proteins
      related to this pathway (CCND1 and BCL2) by immunohistochemistry. RESULTS: We
      observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23)
      and AB (11/11). However, we did not detect expression of the SHH gene in 21/23
      KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P =
      0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high
      levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P =
      0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical
      difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT
      (P = 0.7688), and unicystic and solid AB (P = 0.7521). CONCLUSIONS:
      Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2)
      genes in the SHH pathway leads to the constitutive activation of this pathway in
      KOT and AB and may suggest a mechanism for the development of these types of
      tumors.

PMID- 24930894
TI  - Employing a combinatorial expression approach to characterize xylose utilization
      in Saccharomyces cerevisiae.
AB  - Fermentation of xylose, a major constituent of lignocellulose, will be important
      for expanding sustainable biofuel production. We sought to better understand the
      effects of intrinsic (genotypic) and extrinsic (growth conditions) variables on
      optimal gene expression of the Scheffersomyces stipitis xylose utilization
      pathway in Saccharomyces cerevisiae by using a set of five promoters to
      simultaneously regulate each gene. Three-gene (xylose reductase, xylitol
      dehydrogenase (XDH), and xylulokinase) and eight-gene (expanded with non
      oxidative pentose phosphate pathway enzymes and pyruvate kinase) promoter
      libraries were enriched under aerobic and anaerobic conditions or with a mutant
      XDH with altered cofactor usage. Through characterization of enriched strains, we
      observed (1) differences in promoter enrichment for the three-gene library
      depending on whether the pentose phosphate pathway genes were included during the
      aerobic enrichment; (2) the importance of selection conditions, where some
      aerobically-enriched strains underperform in anaerobic conditions compared to
      anaerobically-enriched strains; (3) improved growth rather than improved
      fermentation product yields for optimized strains carrying the mutant XDH
      compared to the wild-type XDH. 

PMID- 24930893
TI  - Acute binge alcohol administration reverses sleep-wake cycle in Sprague Dawley
      rats.
AB  - BACKGROUND: Binge alcohol drinking is among the most common pattern of alcohol
      consumption in our society. Binge alcohol consumption has serious negative
      consequence on mental and physical health. Although alcohol consumption is known
      to have profound impact on sleep, it is yet unknown as to how binge alcohol
      affects/alters sleep-wakefulness. The objective of this study was to examine the
      effect of acute binge alcohol administration on sleep-wakefulness. METHODS: Male
      Sprague Dawley rats were used in the study. Under standard aseptic surgical
      conditions, rats (N = 7) were implanted with sleep-recording electrodes. After
      postoperative recovery and habituation, baseline sleep-wakefulness was recorded.
      Subsequently, rats were exposed to binge alcohol treatment as follows: One hour
      before light onset, a priming dose of 5 g/kg of alcohol was administered followed
      by 2 subsequent doses (adjusted based on the intoxication level of the rat)
      approximately 8 hours apart. Sleep-wakefulness was continuously recorded for 3
      days post-binge. RESULTS: Acute binge alcohol administration had no significant
      effect on sleep-wakefulness on post-binge Day 1. However, on post-binge Day 2,
      after blood alcohol concentration (BAC) was 0, sleep disruptions were observed
      manifested by a reversal of sleep-wakefulness as evident from insomnia-like
      symptoms (significant increase in wakefulness; significant reduction in nonrapid
      eye movement [NREM] sleep) during the normal sleep (light) period and excessive
      sleep (significant increase in NREM sleep) during the normal active (dark) period
      similar to excessive daytime sleepiness in humans. All sleep-wakefulness changes
      were normalized on Day 3 post-binge. CONCLUSIONS: Alcohol hangover is defined as
      the presence of unpleasant symptoms that peak when BAC is 0. Our results suggest
      that the reversal of sleep-wakefulness accompanies alcohol hangover after binge
      alcohol administration.

PMID- 24930895
TI  - A novel platform for automated high-throughput fluxome profiling of metabolic
      variants.
AB  - Advances in metabolic engineering are enabling the creation of a large number of
      cell factories. However, high-throughput platforms do not yet exist for rapidly
      analyzing the metabolic network of the engineered cells. To fill the gap, we
      developed an integrated solution for fluxome profiling of large sets of
      biological systems and conditions. This platform combines a robotic system for
      (13)C-labelling experiments and sampling of labelled material with NMR-based
      isotopic fingerprinting and automated data interpretation. As a proof-of-concept,
      this workflow was applied to discriminate between Escherichia coli mutants with
      gradual expression of the glucose-6-phosphate dehydrogenase. Metabolic variants
      were clearly discriminated while pathways that support metabolic flexibility
      towards modulation of a single enzyme were elucidating. By directly connecting
      the data flow between cell cultivation and flux quantification, considerable
      advances in throughput, robustness, release of resources and screening capacity
      were achieved. This will undoubtedly facilitate the development of efficient cell
      factories. 

PMID- 24930896
TI  - Selective fluorination of alkyl C-H bonds via photocatalysis.
AB  - We report the generation of cationic N-radicals from Selectfluor(r) via energy
      transfer with anthraquinone as a photocatalyst for the fluorination of
      unactivated C-H bonds. 

PMID- 24930897
TI  - Nature's palette: the search for natural blue colorants.
AB  - The food and beverage industry is seeking to broaden the palette of naturally
      derived colorants. Although considerable effort has been devoted to the search
      for new blue colorants in fruits and vegetables, less attention has been directed
      toward blue compounds from other sources such as bacteria and fungi. The current
      work reviews known organic blue compounds from natural plant, animal, fungal, and
      microbial sources. The scarcity of blue-colored metabolites in the natural world
      relative to metabolites of other colors is discussed, and structural trends
      common among natural blue compounds are identified. These compounds are grouped
      into seven structural classes and evaluated for their potential as new color
      additives. 

PMID- 24930899
TI  - 4-Nitrophenyl- and 4'-nitro-1,1'-biphenyl-4-carboxylates attached to Mo2
      quadruple bonds: ground versus excited state M2delta-ligand conjugation.
AB  - From the reactions between Mo2(T(i)PB)4, where T(i)PB = 2,4,6
      triisopropylbenzoate and two equivalents of the carboxylic acid LH (LH = 4
      nitrobenzoic acid and 4'-nitro[1,1'-biphenyl]-4-carboxylic acid) the compounds
      trans-M2(T(i)PB)2L2 have been prepared: I (L = 4-nitrobenzoate and M = Mo), II (L
      = 4'-nitro-1,1'-biphenylcarboxylate and M = Mo) and III (L = 4-nitrobenzoate and
      M2 = MoW). The compounds have been characterized by (1)H NMR, UV-Vis and steady
      state emission spectroscopy, ns and fs transient absorption spectroscopy and
      cyclic voltammetry. These data are compared with predictions based on electronic
      structure calculations on model compounds where T(i)PB is substituted for
      formate. Together these data indicate stronger ground-state coupling of the
      Mo2delta and ligand pi* systems in I relative to II but this order is reversed in
      the photo excited S1(1)MLCT state. Attempts to prepare the W2 containing analogs
      were unsuccessful. 

PMID- 24930898
TI  - Increased survival using delayed gamma knife radiosurgery for recurrent high
      grade glioma: a feasibility study.
AB  - OBJECTIVE: The current study retrospectively assessed delayed gamma knife
      radiosurgery (GKRS) in the management of high-grade glioma recurrences. METHODS:
      A total of 55 consecutive patients with high-grade glioma comprising 68 World
      Health Organization (WHO) III and WHO IV were treated with GKRS for local
      recurrences between 2001 and 2007. All patients had undergone microsurgery and
      radiochemotherapy, considered as standard therapy for high-grade glioma. Complete
      follow-up was available in all patients; median follow-up was 17.2 months (2.5
      114.2 months). Median tumor volume was 5.2 mL, prescription dose was 20 Gy (14-22
      Gy), and median max dose was 45 Gy (30-77.3 Gy). RESULTS: The patients with WHO
      III tumors showed a median survival of 49.6 months with and a 2-year survival of
      90%. After GKRS of the recurrences, these patients showed a median survival of
      24.2 months and a 2-year survival of 50%. The patients with WHO IV tumors had a
      median survival of 24.5 months with a 2-year survival of 51.4%. After the
      recurrence was treated with GKRS, the median survival was 11.3 months and a 2
      year survival: 22.9% for the WHO IV patients. CONCLUSION: The current study shows
      a survival benefit for high-grade glioma recurrences when GKRS was administered
      after standard therapy. This is a relevant improvement compared with earlier
      studies that had had not been able to provide a beneficial effect timing
      radiosurgery in close vicinity to EBRT.

PMID- 24930900
TI  - Changes in hematological parameters in alpha-thalassemia individuals co-inherited
      with erythroid Kruppel-like factor mutations.
AB  - Phenotypic variations in alpha-thalassemia mainly depend on the defective alpha
      globin gene number. Genetic modifiers of the phenotype of Hemoglobin H (HbH)
      disease were poorly reported, apart from beta-thalassemia allele that was
      identified ameliorating the severity of alpha-thalassemia. Because erythroid
      Kruppel-like factor (KLF1) mutations can modulate the red blood phenotype, we
      evaluated its effect on the alpha-thalassemia phenotype. Overall, we identified
      72 subjects with five different KLF1 heterozygous mutations in 1468 individuals,
      including 65 out of 432 alpha-thalassemia carriers with fetal hemoglobin (HbF)
      levels >=1%, 0 out of 310 carriers with HbF levels <1% and 7 out of 726 HbH
      disease patients. We firstly established the link between KLF1 mutations and
      relatively elevated hemoglobin A2 (HbA2 ) and HbF levels, along with lower mean
      corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values in a group
      of alpha-thalassemia carriers. However, we concluded that KLF1 mutations were not
      significantly linked to HbH disease severity. On the basis of HBA or HBB genotype
      and gender, clinical severity of patients with HbH disease was correctly
      predicted in 73.3% cases. It may improve the screening and diagnostic assessment
      of alpha-thalassemia. 

PMID- 24930902
TI  - Highly branched platinum nanolance assemblies by polyallylamine functionalization
      as superior active, stable, and alcohol-tolerant oxygen reduction
      electrocatalysts.
AB  - The chemical functionalization of platinum (Pt) nanostructures is becoming a new
      trend in electrocatalysts designs. Meanwhile, highly branched Pt nanostructures
      are highly exciting electrocatalysts with high activity and stability owing to
      their specific physical and chemical properties. In this work, the polyallylamine
      (PAH) functionalized Pt nanolance assemblies (Pt NLAs) have been successfully
      synthesized by chemical reduction of PAH-Pt(II) complex using formaldehyde (HCHO)
      in a two-phase water-complex system. The as-prepared Pt NLAs are highly branched
      and three-dimensionally (3D) interconnected nanostructures, which are composed of
      many long Pt nanolances in various directions. PAH functionalization improves the
      electrocatalytic activity of the Pt NLAs for an oxygen reduction reaction (ORR)
      because of high interface proton concentration on the Pt surface and excellent
      anti-oxidation ability of the Pt nanolances. Meanwhile, the PAH molecules bound
      on the Pt NLAs surface act as barrier networks to restrain accessibility of
      alcohol, exhibiting a high ORR selectivity. In addition, the PAH functionalized
      Pt NLAs show excellent durability for the ORR due to their particular 3D
      interconnected structure. The work demonstrates that the PAH functionalized Pt
      NLAs are indeed promising cathodic electrocatalysts for practical application in
      direct alcohol fuel cells. 

PMID- 24930903
TI  - Perspectives on Sexual and Reproductive Health. In this issue.

PMID- 24930901
TI  - RNA interference of GluN1 inhibits neuronal rhythmogenesis in the adult inferior
      olive.
AB  - RNA interference (RNAi) to knockdown N-methyl-D-aspartate receptor (NMDAR)
      function is being investigated to address disorders associated with pathological
      brain rhythms. A motivating finding has been that pharmacological block of NMDARs
      inhibited oscillations in neuronal membrane potential that entrain rhythmic
      bursts of action potentials. To determine whether transient effects of NMDAR
      antagonist drugs to inhibit neuronal rhythmicity can be stably induced with
      genetic specificity, we examined the effects of RNAi of GluN1 protein on the
      subthreshold oscillations (STOs) of neurons in the inferior olive (IO), a
      pacemaking nucleus necessary for motor and cognitive timing. Western blot of
      dissociated neurons demonstrated 90% knockdown of GluN1 after a strong in vivo
      transduction by a dual-microRNA lentiviral vector. GluN1 RNAi in whole-cell
      patched IO neurons blocked both membrane depolarization and STOs typically
      induced by NMDAR activation for up to 54 days without affecting input resistance,
      membrane capacitance, action potential firing, high-threshold Ca(2+) spikes, the
      hyperpolarization-activated current Ih, or the activation of the low-threshold
      Ca(2+) current I(T). Although an off-target effect on Cav3 expression was ruled
      out also by BlastN query, we found that GluN1 RNAi chronically eliminated I(T)
      dependent STOs at resting membrane potential, well below the activation threshold
      of the NMDAR channel. In the context of a recent report showing that NMDAR
      activation induces STOs as it strengthens electrical coupling, the long-term
      block of STOs by GluN1 RNAi may relate to the loss of an essential support
      mechanism. Lentivector-mediated RNAi of GluN1 provides a novel technique for
      future investigations of NMDAR involvement in electrical oscillations and
      behavior.

PMID- 24930912
TI  - High-risk HPV and survival in patients with oral and oropharyngeal squamous cell
      carcinoma - 5-year follow up of a population-based study.
AB  - CONCLUSION: No statistically significant 5-year survival difference was seen in
      patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between
      high-risk HPV-positive and -negative groups in this population-based study.
      OBJECTIVES: To see if the formerly observed higher risk for recurrence or second
      primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds
      to worse survival. METHODS: A total of 128 consecutive, previously untreated
      patients with OOPSCC, who were part of a population-based case-control study in
      southern Sweden during 2000-2004, were included. A mouthwash sample was collected
      and exfoliated cells were collected with cotton-tipped swabs from the tonsillar
      fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase
      chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between
      HPV-negative and HPV-positive patients were calculated. The relationship between
      age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal
      tumours were assessed separately. RESULTS: Mean DSS in months was 80.7/68.6 (high
      risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and
      67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal
      tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage
      all showed significant differences in DSS. For oropharyngeal tumours, no
      significant difference regarding DSS was found.

PMID- 24930913
TI  - Facial nerve preservation in geniculate ganglion hemangiomas.
AB  - CONCLUSIONS: Facial nerve preservation was related to tumor size, and the
      patients with facial nerve preservation obtained better recovery. Hence it is
      necessary to perform surgical removal as soon as possible. OBJECTIVE: To study
      facial nerve preservation in patients with geniculate ganglion (GG) hemangiomas.
      METHODS: Twelve patients who had GG hemangiomas were managed at a single
      institute. All patients underwent total tumor removal, and the surgeon attempted
      to preserve the facial nerve. Tumor size was measured by MRI, and the patients
      were divided into two groups according to tumor size: larger size group (>=10 mm)
      and smaller size group (<10 mm). RESULTS: Generally, the facial nerve was
      successfully preserved in 10 of 12 cases (83.30%), and nerve grafting was
      required in 2 cases. Seven of 10 patients (70%) with nerve intact recovered to
      grade I or grade II, while the 2 cases with nerve grafting recovered to grade III
      or grade IV. Among the smaller size group, the facial nerves of all patients
      (100%) were intact. In contrast, only one of three patients (33.3%) in the larger
      size group maintained nerve integrity after surgery.

PMID- 24930914
TI  - Variations in treatment of peritonsillar abscess in four Nordic countries.
AB  - CONCLUSION: In four Nordic countries, peritonsillar abscess (PTA) patients are
      treated rather differently. OBJECTIVES: To study how such patients are treated in
      those countries. METHODS: The 81 chief physicians of otorhinolaryngology
      departments of all central hospitals in Denmark (n = 15), Norway (n = 19), Sweden
      (n = 27), and Finland (n = 20) received a multiple-choice questionnaire. RESULTS:
      A total of 73 physicians (90%) replied. The largest differences arose in treating
      patients with intravenous versus per oral antibiotics, and treating as inpatients
      versus outpatients. In Finland, 50% of PTA patients aged >16 years were treated
      as inpatients and 50% as outpatients, whereas the respective quotas in Sweden
      were 9 and 91%, Norway 19 and 81%, and Denmark 33 and 67%. Of Finnish physicians,
      30% treated their patients primarily with oral antibiotics, 70% with intravenous
      antibiotics; in Sweden 91 vs 9%, Norway 53 vs 47%, and Denmark 18 vs 82%. In
      Denmark, almost all patients were operated on immediately, whereas in the other
      three countries, especially Sweden, operations more often were performed after a
      recovery period. Combining metronidazole with penicillin or cephalosporins was
      most common in Denmark: 58% reported usage, compared with 30% in Finland, 16% in
      Norway, and 4% in Sweden.

PMID- 24930915
TI  - Immunoglobulin G4-related disease in a psoriasis vulgaris patient treated with
      ustekinumab.

PMID- 24930918
TI  - Editorial.

PMID- 24930917
TI  - Glycoborinine induces apoptosis through mitochondrial pathway in HepG2 cells.
AB  - Glycoborinine (GB), a natural carbazole alkaloid isolated from Glycosmis
      pentaphylla, has been shown to be a potential molecule against cancer cells. In
      this study, the cell-signaling pathway of its anti-tumor activity was
      investigated. MTT assay result showed that GB inhibited HepG2 cell proliferation
      in a dose- and time-dependent manner and 50% inhibiting concentration (IC50) of
      GB-induced cell death was 39.7 MUM for a period of 48 h. GB-induced HepG2
      apoptosis was confirmed by Hochest 33258 staining and PI staining. The level of
      reactive oxygen species (ROS) was measured with H2DCF-DA staining and the change
      of mitochondrial membrane potential (?Psi(m)) was analyzed with tetrechloro
      tetraethylbenzimidazolcarbocyanine iodide (JC-1) probe. Results showed that GB at
      12.5, 25, and 50 MUM promoted ROS production. GB induced HepG2 apoptosis through
      a mitochondrial apoptotic pathway, which was demonstrated by GB-induced increase
      in the ratio of Bax/Bcl-2, cytochrome C release, the ratio of cleaved caspase
      3/procaspase-3, and the ratio of cleaved poly ADP-ribose polymerase (cleaved
      PARP)/poly ADP-ribose polymerase (PARP). To summarize, this study demonstrated
      that GB could induce HepG2 apoptosis through the mitochondrial-dependent pathway,
      which might provide a promising approach to cure liver cancer with GB.

PMID- 24930919
TI  - Catatonia in the elderly.
AB  - Catatonia in geriatric patients has been insufficiently investigated. We reviewed
      71 case descriptions from 45 studies to clarify the phenomenology, diagnosis,
      etiology, and treatment of catatonia in the elderly. In elderly patients,
      catatonia is frequently observed in association with general medical conditions.
      In patients with a history of depression or schizophrenia, physicians
      occasionally overlook the medical conditions because they believe the previous
      psychosis to be the cause of the catatonic features. Despite historical
      discussions of a relation between the disorders, the number of patients with
      catatonia and a prior diagnosis of schizophrenia or another psychotic disorder is
      not large. A diagnosis of catatonia should be considered in cases of atypical
      "collapse" in elderly patients with a previous psychiatric history of mood
      disorder. Catatonia due to anxiety/adjustment disorder is quite rare, whereas
      catatonia in association with neuroleptic malignant syndrome is fairly common.
      For early commencement of treatment, early detection of catatonia in the elderly
      is important. In studies of psychotropic drug treatment, many authors observed a
      beneficial response to lorazepam in catatonic patients. For medication-refractory
      patients, electroconvulsive therapy should be considered. It is important to
      prevent the development of venous thrombosis as a serious complication in
      stuporous catatonic patients. 

PMID- 24930916
TI  - Clinical and virological characteristics associated with severe acute hepatitis
      B.
AB  - To identify early predictors of a severe or fulminant course in patients with
      acute viral hepatitis B (AVH-B). One hundred and thirty-eight patients with
      symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each
      patient, the demographics, risk factors for the acquisition of hepatitis B virus
      (HBV) infection, clinical, biochemical and virological data (HBV DNA, HBV DNA
      sequences) were recorded and analysed. The HBV mutants in the polymerase region
      were sought in 110 (87%) patients by direct sequencing, and the rtM204V/I
      mutations also by an allele-specific PCR. AVH-B was severe in 13 (9.4%) of the
      138 patients enrolled, fulminant in 6 (4.3%) and with a normal clinical course in
      119. The 19 patients with severe or fulminant AVH-B more frequently than the 119
      with a normal course stated intravenous drug use (63.2% versus 36.1%, p 0.04) and
      were HBV-DNA negative (31.6% versus 11.8%, p 0.03) and anti-hepatitis C virus
      (HCV) positive (57.9% versus 19.3%, p 0.0008); the prevalences of different HBV
      genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B.
      A multivariate logistic regression analysis identified a pre-existing HCV chronic
      infection as the only factor independently associated with a severe or fulminant
      clinical course of AVH-B (OR 4.89, 95% CI 1.5-15.94, p 0.01). A pre-existing HCV
      chronic infection was identified as the only factor independently associated with
      a severe clinical presentation of acute hepatitis B, an association most probably
      due to the combination of the liver lesions caused by acute hepatitis B and the
      pre-existing histological abnormalities related to HCV chronic infection. 

PMID- 24930920
TI  - Dyskinesia and soft neurological signs in schizophrenia: a comparative study.
AB  - Objective. Several neurological abnormalities can be found at a greater frequency
      in patients with schizophrenia, including neurological soft signs (NSS) and signs
      of the "pyramidal" and "extrapyramidal" systems. We aimed to explore the
      frequency of movement disorders in patients with antipsychotic naive
      schizophrenia and to compare and contrast with antipsychotic-treated patients and
      healthy controls. Methods. Twenty-two antipsychotic naive schizophrenic patients,
      22 antipsychotic treated patients and 22 healthy control subjects were assessed
      by Neurological Evaluation (NES), Abnormal Involuntary Movements (AIMS), and
      Positive and Negative Syndrome (PANSS) Scales. Results. The NES scores of the
      never-medicated schizophrenic group were significantly higher than those of
      normal controls but did not differ significantly from the medicated group.
      Dyskinesia rates in the both schizophrenic groups were higher than in healthy
      controls. Medicated and non-medicated schizophrenic patient scores did not differ
      in AIMS with regard to facial and oral movements, but medicated patients scored
      higher than non-medicated subjects with respect to extremity movements.
      Conclusion. Our data suggest that: soft neurological signs and abnormal
      involuntary movements in the facial region are more prevalent in patients with
      schizophrenia, whether they are medicated or antipsychotic naive. On the
      contrary, abnormal involuntary movements in the trunk and the extremities seem to
      be associated with medication. 

PMID- 24930921
TI  - Olanzapine in subjects with a first-episode psychosis non-responsive, intolerant
      or non-compliant to a first-line trial of risperidone.
AB  - Objective. Investigation of the efficacy and tolerability of olanzapine (OLZ) as
      second-line treatment in subjects with a first-episode psychosis (FEP) who had
      been non-responsive, intolerant or non-compliant to Risperidone (RIS). Methods.
      The Early Psychosis Prevention and Intervention Centre in Melbourne admitted 786
      FEP subjects between 1998 and 2000. Data were collected from subjects' medical
      records (MR). The objective was to evaluate the efficacy of OLZ as measured by
      CGI-S, GAF, SOFAS and remission rates as well as tolerability. Results. A total
      of 104 subjects were switched because of non-response (38%), non-compliance
      (15%), or intolerance (47%). Independent of reasons for switch, significant
      symptomatic and functional improvements were detected. Overall, 46 subjects (44%)
      achieved full remission. Regression analysis indicated that reason for switch did
      not predict full remission. Significantly more extrapyramidal side effects
      (P<0.001) were related to previous RIS and significantly more weight gain to the
      subsequent OLZ treatment (P<0.001). Conclusions. OLZ may be an effective
      alternative for FEP patients who are non-responsive, intolerant or non-compliant
      to RIS. The decision to switch to OLZ must be weighted against the greater risk
      of weight gain with its risks for medical complications and its psychosocial
      consequences. 

PMID- 24930922
TI  - Use of polypharmacy and self-reported mood in outpatients with bipolar disorder.
AB  - Objective. As polypharmacy is routinely used for the treatment of bipolar
      disorder, the relation between the daily number of psychotropic medications and
      self-reported mood was investigated. Method. Eighty patients (35 men and 45
      women) with a diagnosis of bipolar disorder I or II, recruited from academic
      centres, entered their mood, sleep, and psychotropic medications for 3 months
      into ChronoRecord software. A total of 8662 days of data was received (mean 114.7
      days/per patient). Results. Seventy-nine patients took a mean of 3.8 medications
      daily (SD 1.7; range 1-9); one took none. Of these patients, 73 (92.4%) took mood
      stabilizers, 47 (58.8%) took antidepressants, 31 (38.8%) took antipsychotics, 34
      (42.5%) took benzodiazepines and 17 (21.1%) took thyroid hormones. Patients
      reporting normal mood more frequently took fewer medications; the Pearson
      correlation coefficient between the number of medications and the percent of days
      normal was -0.481 (P < 0.001). Grouping by number of medications, ANOVA analysis
      showed those taking fewer medications reported normal mood more frequently
      (P<0.001). Conclusion. Combination treatment regimens are routinely prescribed
      for bipolar disorder. Patients reporting normal mood more frequently took a fewer
      number of daily medications. Studies are needed to better identify those patients
      who would benefit from polypharmacy and to optimise the combinations of
      medications for patients with refractory disorder. 

PMID- 24930923
TI  - Group cognitive behaviour therapy in obsessive-compulsive disorder (OCD): a
      controlled study.
AB  - Objective. This study compared cognitive behavioural therapy (CBT) with
      relaxation therapy (RT) as group-based treatments for obsessive compulsive
      disorder (OCD). Hitherto, most studies of group CBT in OCD have used uncontrolled
      designs. Methods. Forty-one patients with OCD were assigned to group CBT or group
      RT. Each therapy comprised 12 weekly sessions and participants were assessed
      primarily on the Y-BOCS. Secondary outcome measures for depressive and anxiety
      symptoms were also collected. All outcome measures were recorded by blind raters.
      Results. The percentage of drop-outs in the RT condition (35%) exceeded the
      number in the CBT condition (4%). However, there were no differences between
      group CBT and group RT in terms of improvement on primary or secondary outcome
      measures. Conclusion. Our findings suggest that the apparent benefits of group
      CBT may not relate specifically to the CBT element of treatment and also
      underscore the importance of controlled studies in this area. However, the
      disparity in drop-out rate between conditions suggests that group CBT is more
      acceptable to patients than group RT. 

PMID- 24930924
TI  - Evaluation of an antipsychotic information sheet for patients.
AB  - Introduction. The objective of this study was to develop a decision aid that
      patients and clinicians might use to help the patient in the process of selecting
      an antipsychotic medication. In addition, we aimed to determine the antipsychotic
      that patients would choose given the information contained in the leaflet.
      Method. We designed a questionnaire for patients to appraise the contents of the
      leaflet, their understanding of the leaflet and the potential impact of the
      leaflet on compliance and therapeutic relationship between patient and doctor.
      Results. We recruited 30 stable patients with a diagnosis of a psychotic illness
      to evaluate the leaflet and to determine patient choice. Over 90% of patients
      felt that the leaflet improved their knowledge of antipsychotic medication.
      Seventy-six percent of patients agreed that the leaflet contained the right type
      and amount of information. Seventy percent of respondents believed the leaflet
      would improve the trust between them and their doctors, and almost half (47%)
      stated they were more likely to take their medicine after reading the leaflet.
      Forty percent of patients would prefer to switch antipsychotic medication, with
      quetiapine being the most frequently preferred option. Conclusion. The results
      indicate that, for patients in the stable phase of their illness, the leaflet is
      a useful tool in selecting an antipsychotic medication and may represent a way
      forward in improving outcomes in patients with psychotic disorders. A larger
      study examining outcomes using this tool would establish its clinical utility. 

PMID- 24930925
TI  - Relationship between serum valproate and lithium levels and efficacy and
      tolerability in bipolar maintenance therapy.
AB  - Background. In spite of widespread recognition of the importance of maintenance
      treatment for bipolar disorder, there are relatively few available well-designed
      clinical trials that have provided rigorous evidence for the efficacy of specific
      agents. One approach used effectively in analyses of lithium studies has been the
      stratification of efficacy and tolerability results based on serum drug
      concentrations. Therefore, we conducted a similar analysis of the efficacy of
      divalproex or lithium, based on serum concentrations in the maintenance treatment
      of bipolar I disorder in a recent 12-month placebo-controlled trial. Methods.
      This was a post-hoc analysis of results obtained in a 12-month, double-blind,
      placebo-controlled trial of divalproex and lithium involving 372 patients (intent
      to-treat). The patient set was stratified into four therapeutic drug
      concentration ranges (Non-therapeutic, Low Therapeutic, Medium Therapeutic, and
      High Therapeutic) for both divalproex and lithium. Efficacy measures were Kaplan
      Meier survival analyses of time to discontinuation for any reason, time to
      discontinuation for a protocol-defined manic episode, and time to discontinuation
      for a manic or depressive episode. Results. Significant differences between
      divalproex at the Medium Therapeutic range (75-99.9 ug/ml) and placebo were
      demonstrated in Kaplan-Meier survival results for discontinuation for any reason
      (median survival time: divalproex, 8 months; placebo, 4 months; P<0.05) and for
      discontinuation for a manic or depressive episode (median survival time:
      divalproex, 8 months; placebo, 3 months, P=0.003). At 12 months, the proportion
      of divalproex-treated patients (Medium Therapeutic range) who did not discontinue
      for a protocol-defined manic episode (85%) was higher than the proportion of
      lithium (Medium Therapeutic range; 70%) or placebo-treated (83%) patients.
      Conclusions. Divalproex at the Medium Therapeutic range provided significantly
      better bipolar maintenance treatment response than placebo in survival analyses,
      suggesting a possible serum concentration target range for clinicians in
      providing optimal treatment response. The value of this analytic approach, used
      for the first time here for divalproex, is discussed, along with a call for
      further research into optimal therapeutic drug levels. 

PMID- 24930926
TI  - Divalproex for the treatment of posttraumatic stress disorder: a retrospective
      chart review.
AB  - Objective. Open label trials of divalproex in the treatment of posttraumatic
      stress disorder (PTSD) show positive results. The objective of this study was to
      examine the therapeutic effects of divalproex in a larger naturalistic sample of
      patients with PTSD. Methods. A retrospective analysis was performed on 325
      veteran charts identified through a computerized search of PTSD diagnosis matched
      with pharmacy records (any form of divalproex). The medication names, doses,
      labs, and dates (except for the divalproex index visit) were blackened. An
      investigator blinded to the order of visits and blackened information rated the
      progress notes preceding and following psychopharmacological intervention with
      divalproex with the Clinical Global Impression Scale for Improvement (CGI-I).
      Results. Fifty patients met eligibility criteria. Three were treated with
      divalproex monotherapy and 47 were treated adjunctively. The improved endpoint
      CGI-I differed significantly from "no change" (P<0.000001). Twenty-five (50%)
      were rated as very much or much improved on the CGI-I. Patients treated in
      primary care had a greater improvement compared to those in the mental health
      setting (P<0.005). Divalproex dosage and serum valproic acid levels (n=37) were
      well correlated (r = 0.57, P<0.0005). Conclusion. Divalproex treatment improves
      the global clinical function of veterans with PTSD. Further controlled study is
      warranted. 

PMID- 24930927
TI  - Two cases of neuroleptic-induced prolonged extrapyramidal symptoms.
AB  - Neuroleptic-induced extrapyramidal symptoms (EPS) are generally categorized as
      acute, withdrawal and tardive EPS. Here, we report two cases of a unique late
      onset, long-lasting EPS (e.g., prolonged EPS); in those cases, EPS appeared a few
      months following initiation of haloperidol and lasted for a few months after
      significant reduction or complete withdrawal of neuroleptics. Case 1, a 41-year
      old female, began to exhibit EPS such as bradykinesia, rigidity and parkinsonian
      gait 4 months after the haloperidol treatment. Her rigidity was ameliorated by a
      reduction of haloperidol; however, reduction of neuroleptics made it difficult
      for her to maintain a seated posture because of an imbalance of muscle tonus. Her
      EPS continued for 9 months even after haloperidol was switched to very low doses
      of thioridazine (10 mg/day). Case 2 is a 42-year-old female. She exhibited EPS
      including dysphagia and a difficulty in opening her mouth 3 months after the
      haloperidol treatment began. Her EPS lasted for 45 days, even after complete
      withdrawal of neuroleptics. The EPS observed in these two cases occurred even
      after prolactin levels became normal. "Prolonged EPS" is a unique subclass of
      neuroleptic-induced reversible EPS that might involve the coexistence of hypo-
      and hyper-dopaminergic transmission, especially in patients who show very low
      tolerance to neuroleptics. 

PMID- 24930928
TI  - Bupropion is effective in depression in narcolepsy.
AB  - Narcolepsy is a rare disorder characterised by sleep disturbances, cataplexy,
      sleep paralysis and hypnagogic, hypnopompic hallucinations. Although several
      treatment modalities, such as tricyclic antidepressants or selective serotonin
      reuptake inhibitors, have been used to treat different symptoms, there is no
      definite treatment for narcolepsy. Modafinil or amphetamine-like stimulants, such
      as dexamphetamine or methylphenidate, are used to treat sleepiness. Our case was
      a 58-year-old woman who was diagnosed as narcolepsy cataplexy syndrome. Her
      Epworth Sleepiness Scale (ESS) score was 14 and Beck Depression Inventory (BDI)
      score was 29 in the first evaluation. Imipramine and modafinil were begun for the
      treatment, but there was no improvement in her symptoms. Subsequently, bupropion
      was started at 150 mg/day and then dosage was increased to 300 mg/day. She was
      asymptomatic at the end of 3 months. To our knowledge, this is the second
      depressive narcoleptic patient who has responded to 300 mg/day of bupropion. 

PMID- 24930929
TI  - Bipolar disorder after traumatic brain injury.
AB  - Objective. We report the case of a 47-year-old man with no psychiatric
      antecedents who developed manic and depressive symptoms after traumatic brain
      injury (TBI). Methods and results. Findings on neurobehavioral examination,
      neuropsychological test battery, electrophysiological and imaging exams suggested
      the presence of a diffuse cerebral injury with a predominance of left fronto
      temporal findings. Conclusions. This case demonstrates that TBI may cause
      vulnerability to psychiatric disorders, with long latency periods, and that its
      course may be independent of cognitive impairment and recovery. 

PMID- 24930930
TI  - Incipient neuroleptic malignant syndrome with quetiapine/paroxetine combination
      treatment: atypical presentation and early, successful rechallenge with
      olanzapine.
AB  - A 26-year-old caucasian male developed incipient neuroleptic malignant syndrome
      (NMS) during the course of paranoid schizophrenia with catatonic signs at
      admission, while on quetiapine/paroxetine combination treatment. The clinical
      presentation was "atypical", but increased creatine kinase levels and positive
      myoglobinemia were highly suggestive of the diagnosis. Of note, the patient was
      successfully rechallenged with olanzapine. The implications of the drug regimen
      and of the catatonic presentation are discussed. 

PMID- 24930931
TI  - Anxiety can be a harbinger of early onset dementia.
AB  - We report an interesting case study of a 58-year-old woman who had early onsct
      dementis which initially presented with marked features of anxiety that masked
      her cognitive impairment. She was treated for anxiety for about 2 years. Her
      anxiety symptoms caused hindrance in detecting dementis at the early stage. 

PMID- 24930932
TI  - Speaker abstracts.

PMID- 24930933
TI  - Assessment of endothelial dysfunction in Asian Indian patients with chronic
      kidney disease and changes following renal transplantation.
AB  - BACKGROUND: Endothelial dysfunction may explain increased cardiovascular risk in
      patients with chronic kidney disease (CKD). METHODS: Brachial artery was imaged
      during reactive hyperemia (endothelium-dependent, flow-mediated dilatation, FMD)
      and during glyceryl trinitrate-mediated dilatation (nitroglycerine-mediated
      dilatation, NMD, endothelium-independent) in 108 patients with CKD and three
      months following renal transplantation (RT) in 60 of them. RESULTS: Patients with
      CKD had significantly lower FMD vs. controls (9.1% vs. 18.3%, p < 0.001) while
      NMD was comparable (19.8% vs. 21.8%, p = ns). Impaired FMD (<4.5%) was observed
      in 26.8% patients with CKD and was more common in those on hemodialysis (HD;
      28.4% vs. 15.4%) vs. those not on dialysis. FMD for patients with glomerular
      filtration rate (GFR) 15-60 vs. <15 mL/min/1.73 m(2) was 12.9% and 8.8% (p =
      0.05; respectively -29% and -52% lower vs. controls), indicating reduced FMD with
      increasing CKD severity. There was +72% increase in FMD following RT (9.1 to
      15.7%, p < 0.001) while mean NMD was unchanged. Following RT, only 3.3% had
      impaired FMD. CONCLUSIONS: Patients with CKD have endothelial dysfunction as
      evidenced by reduced FMD. Decreased FMD indicating worsening endothelial function
      was noted with increasing severity of CKD. Within three months of RT, there was
      significant improvement in FMD, while NMD values did not change.

PMID- 24930934
TI  - Could deep brain stimulation help with driving for patients with Parkinson's?
AB  - For mobility impaired people with Parkinson's disease (PD), driving a car is
      important to maintain independency. But driving ability is getting worse with
      disease progression. Meanwhile surgical treatment with deep brain stimulation
      (DBS) of the subthalamic nucleus is done routinely in advanced PD, but it is
      unknown how DBS might affect driving. In a driving simulator setting, we found PD
      patients undergone DBS surgery to drive safer than even less clinically affected
      PD patients treated with medication alone. Furthermore, patients with DBS surgery
      drove better under stimulation than under medication. In conclusion, DBS of the
      subthalamic nucleus appears to be beneficial for driving in PD patients,
      potentially due to non-motor effects on controlling the vehicle in the simulator
      setting. Nevertheless, results of this first pilot study on driving in PD
      patients with DBS should not encourage patients or physicians to consider DBS
      only to improve or regain driving competence. 

PMID- 24930936
TI  - Electrical stimulation of cerebellar fastigial nucleus: mechanism of
      neuroprotection and prospects for clinical application against cerebral ischemia.
AB  - For around two decades, electrical fastigial nucleus stimulation (FNS) has been
      demonstrated to induce neuroprotection involving multiple mechanisms. In this
      review, we summarize the protective effects of FNS against cerebral ischemia
      through the inhibition of electrical activity around the lesion, excitotoxic
      damage on neurons, and brain inflammatory response, as well as apoptosis.
      Moreover, FNS has been reported to promote nerve tissue repair, reconstruction,
      and neurological rehabilitation and improve stroke-related complications
      including poststroke cognitive dysfunction, depression, and abnormal heart rate
      variability. We thus further discuss the potential of FNS for clinical
      applications. Given the absence of any risk of inducing sublethal damage, FNS may
      offer a new approach to preconditioned neuroprotection against cerebral ischemia.

PMID- 24930937
TI  - Oligoalanine-modified Pluronic-F127 nanocarriers for the delivery of curcumin
      with enhanced entrapment efficiency.
AB  - Curcumin is a naturally occurring compound that has been shown to have anti
      oxidant, anti-inflammatory, and anti-carcinogenic activities. However, its
      pharmaceutical potential has been limited due to its low solubility in water. The
      use of amphiphilic nanocarriers is an attractive and simple method to solubilize
      curcumin. In this study, we modified Pluronic F-127 [poly(ethylene glycol)100
      block-poly(propylene glycol)65-block-poly(ethylene glycol)100] (PF-127) with
      oligomers of alanine, an amino acid, to increase the drug entrapment efficiency
      of curcumin through core stabilization. Alanine-modified PF-127 exhibited lower
      critical micelle concentration and decreased molecular motion in both the
      hydrophilic and hydrophobic segments ((1)H NMR). Nanocarriers in the size range
      of 54.2-68.4 nm were observed. Entrapment efficiency of curcumin increased by at
      most 66% (from 25.3 to 91.3%) and the difference in solubility was clearly
      visualized by increased transparency of the nanocarrier solutions. Curcumin was
      released continuously up to 120 h from modified carriers, while drug release from
      unmodified carriers plateaued within 24 h. These modified nanocarriers exhibited
      no cytotoxicity and more efficiently delivered drugs to HeLa cells as confirmed
      by fluorescent microscopy. This study demonstrated that alanine modification of
      FDA-approved PF-127 affects copolymer nanoassembly and has a profound impact on
      curcumin loading and possibly on other hydrophobic drugs as well.

PMID- 24930935
TI  - CXCR3 modulates glial accumulation and activation in cuprizone-induced
      demyelination of the central nervous system.
AB  - BACKGROUND: The functional state of glial cells, like astrocytes and microglia,
      critically modulates the course of neuroinflammatory and neurodegenerative
      diseases and can have both detrimental and beneficial effects. Glial cell
      function is tightly controlled by cellular interactions in which cytokines are
      important messengers. Recent studies provide evidence that in particular
      chemokines are important modulators of glial cell function. During the course of
      CNS diseases like multiple sclerosis or Alzheimer's disease, and in the
      corresponding animal models, the chemokines CXCL9 and CXCL10 are abundantly
      expressed at sites of glial activation, arguing for an important role of these
      chemokines and their corresponding receptor CXCR3 in glial activation. To clarify
      the role of this chemokine system in glial cell activation, we characterized the
      impact of CXCR3 on glial activation in a model of toxic demyelination in which
      glial activation without a prominent influx of hematogenous cells is
      prototypical. METHODS: We investigated the impact of CXCR3 on cuprizone-induced
      demyelination, comparing CXCR3-deficient mice with wild type controls. The
      clinical course during cuprizone feeding was documented for five weeks and for
      the subsequent four days withdrawal of the cuprizone diet (5.5 weeks). Glial
      activation was characterized using histological, histomorphometric and phenotypic
      analysis. Molecular analysis for (de)myelination and neuroinflammation was
      applied to characterize the effect of cuprizone on CXCR3-deficient mice and
      control animals. RESULTS: CXCR3-deficient mice displayed a milder clinical course
      during cuprizone feeding and a more rapid body weight recovery after offset of
      diet. In the CNS, CXCR3 deficiency significantly attenuated the accumulation and
      activation of microglia and astrocytes. Moreover, a deficiency of CXCR3 reduced
      the expression of the microglial activation markers CD45 and CD11b. Compared to
      controls, we observed a vast reduction of RNA levels for proinflammatory
      cytokines and chemokines like Ccl2, Cxcl10, Tnf and Il6 within the CNS of
      cuprizone-treated mice. Lastly, CXCR3 deficiency had no major effects on the
      course of demyelination during cuprizone feeding. CONCLUSIONS: The CXCR3
      chemokine system is critically involved in the intrinsic glial activation during
      cuprizone-induced demyelination, which significantly modulates the distribution
      of glial cells and the local cytokine milieu.

PMID- 24930939
TI  - Mu rhythm and rhythmic midtemporal discharges in REM sleep.

PMID- 24930938
TI  - Prognostic EEG patterns in patients resuscitated from cardiac arrest with
      particular focus on Generalized Periodic Epileptiform Discharges (GPEDs).
AB  - STUDY AIMS: We assessed clinical and early electrophysiological characteristics,
      in particular Generalized Periodic Epileptiform Discharges (GPEDs) patterns, of
      consecutive patients during a 1-year period, hospitalized in the Intensive Care
      Unit (ICU) after resuscitation following cardiac arrest (CA). PATIENTS AND
      METHODS: Consecutive patients resuscitated from cardiac arrest (CA) with first
      EEG recordings within 48hours were included. Clinical data were collected from
      hospital records, in particular therapeutic hypothermia. Electroencephalograms
      (EEGs) were re-analyzed retrospectively. RESULTS: Sixty-two patients were
      included. Forty-two patients (68%) were treated with therapeutic hypothermia
      according to international guidelines. Global mortality was 74% but not
      significantly different between patients who benefited from therapeutic
      hypothermia compared to those who did not. All the patients who did not have an
      initial background activity (36/62; 58%) died. By contrast, initial background
      activity was present in 26/62 (42%) and among these patients, 16/26 (61%)
      survived. Electroencephalography demonstrated GPEDs patterns in 5 patients, all
      treated by therapeutic hypothermia and antiepileptic drugs. One of these survived
      and showed persistent background activity with responsiveness to benzodiazepine
      intravenous injection. CONCLUSION: Patients presenting suppressed background
      activity, even when treated by hypothermia, have a high probability of poor
      outcome. Thorough analysis of EEG patterns might help to identify patients with a
      better chance of survival.

PMID- 24930940
TI  - Emotional facial expression processing in depression: data from behavioral and
      event-related potential studies.
AB  - Behavioral literature investigating emotional processes in depressive populations
      (i.e., unipolar and bipolar depression) states that, compared to healthy
      controls, depressive subjects exhibit disrupted emotional processing, indexed by
      lower performance and/or delayed response latencies. The development of brain
      imaging techniques, such as functional magnetic resonance imaging (fMRI),
      provided the possibility to visualize the brain regions engaged in emotional
      processes and how they fail to interact in psychiatric diseases. However, fMRI
      suffers from poor temporal resolution and cognitive function involves various
      steps and cognitive stages (serially or in parallel) to give rise to a normal
      performance. Thus, the origin of a behavioral deficit may result from the
      alteration of a cognitive stage differently situated along the information
      processing stream, outlining the importance of access to this dynamic "temporal"
      information. In this paper, we will illustrate, through depression, the role that
      should be attributed to cognitive event-related potentials (ERPs). Indeed, owing
      to their optimal temporal resolution, ERPs can monitor the neural processes
      engaged in disrupted cognitive function and provide crucial information for its
      treatment, training of the impaired cognitive functions and guidelines for
      clinicians in the choice and monitoring of appropriate medication for the
      patient. 

PMID- 24930941
TI  - "All that glitters is not ... alone". Congruity effects in highly and less
      predictable sentence contexts.
AB  - CONTEXT: Using natural connected speech, the aim of the present study was to
      examine the semantic congruity effect (i.e. the difference between semantically
      incongruous and congruous words) in sentence contexts that generate high or
      moderate final word expectancies. METHODS: We used sentences with two levels of
      word expectancy in the auditory modality: familiar proverbs (that generate high
      final word expectancy), and unfamiliar sentences (that generate only moderate
      final word expectancy). RESULTS: Results revealed an early congruity effect (0
      200 ms) that developed across all scalp sites for familiar proverbs but not for
      unfamiliar sentences. By contrast, typical centro-parietal N400 and Late
      Positivity Component congruity effects developed later (200-500 ms and 600-900 ms
      ranges) for both familiar proverbs and unfamiliar sentences. DISCUSSION: We argue
      that the early congruity effect for proverbs comprises both a Phonological
      Mismatch Negativity, reflecting the processing of the acoustic/phonological
      mismatch between the expected (congruous) and unexpected (incongruous) sentence
      completions and a typical N400 semantic congruity effect with an unusual short
      latency because final words can be predicted from the unusually high contextual
      constraints of familiar proverbs. These results are considered in the light of
      current views of anticipation and prediction processes in sentence contexts.

PMID- 24930942
TI  - Distinction between essential and physiological tremor using Hilbert-Huang
      transform.
AB  - Neurophysiological investigation, based on accelerometric (ACC) and
      electromyographic (EMG) recordings, is an essential step in the diagnosis of
      tremor. Among various signal analysis methods, fast Fourier transform (FFT) is
      the most frequently used in this domain. However, FFT has several limitations:
      first, it assumes that tremor is a periodic and linear signal, which is not true;
      second, it cannot distinguish between different types of tremor, when their
      frequency overlap in similar range, such as essential tremor (ET) and
      physiological tremor (PT). Therefore, we decided to apply a non-linear method of
      signal analysis based on empirical mode decomposition (EMD) and Hilbert Huang
      transform (HHT), according to various procedures and compared to a more classical
      FFT approach. A first group of 8 healthy subjects with PT and a second group of 8
      patients with ET were included in this study. At individual level, FFT was
      effective to highlight ET in the 8 patients, but PT in only 2 subjects. The EMD
      HHT procedures performed better than FFT, revealing a common peak of PT in all
      subjects. Moreover, at group level, our EMD-HHT method allowed to clearly
      differentiate the two groups, especially by giving evidence for the existence of
      low frequency oscillations (around 4Hz) in subjects with PT. Although their
      physiological origin remains largely unknown, such slow oscillations seem to be
      of great importance to highlight PT and they have been much underestimated in the
      literature. Our original EMD-HHT approach is able to provide substantial
      improvement in the neurophysiological characterisation of the different types of
      tremor, especially for diagnostic application. 

PMID- 24930943
TI  - Motor excitability measurements: the influence of gender, body mass index, age
      and temperature in healthy controls.
AB  - STUDY AIMS: The technique of threshold tracking to test axonal excitability gives
      information about nodal and internodal ion channel function. We aimed to
      investigate variability of the motor excitability measurements in healthy
      controls, taking into account age, gender, body mass index (BMI) and small
      changes in skin temperature. MATERIALS AND METHODS: We examined the left median
      nerve of 47 healthy controls using the automated threshold-tacking program,
      QTRAC. Statistical multiple regression analysis was applied to test relationship
      between nerve excitability measurements and subject variables. RESULTS:
      Comparisons between genders did not find any significant difference (P>0.2 for
      all comparisons). Multiple regression analysis showed that motor amplitude
      decreases with age and temperature, stimulus-response slope decreases with age
      and BMI, and that accommodation half-time decrease with age and temperature.
      CONCLUSION: The changes related to demographic features on TRONDE protocol
      parameters are small and less important than in conventional nerve conduction
      studies. Nonetheless, our results underscore the relevance of careful temperature
      control, and indicate that interpretation of stimulus-response slope and
      accommodation half-time should take into account age and BMI. In contrast, gender
      is not of major relevance to axonal threshold findings in motor nerves.

PMID- 24930944
TI  - An easily applicable alternative method for warming cold limbs in nerve
      conduction studies.
AB  - OBJECTIVE: Warming cold limbs by hot water immersion prior to nerve conduction
      studies may be cumbersome in certain patients. The aim of the present study is to
      test whether application of hot packs would be as efficient as hot water
      immersion. METHODS: Cold limbs of 10 healthy volunteers were warmed: in half of
      subjects by hot packs and, after cooling down, by hot water immersion; vice versa
      in the other half. Motor and sensory nerve conduction studies of upper and lower
      extremities were performed before and after warming with two different methods.
      RESULTS: There are no relevant differences in temperatures or nerve conduction
      velocities after warming with either hot packs or water. CONCLUSION: Hot packs
      are as effective as hot water immersion for warming cold limbs prior to
      electrodiagnostic testing. Since hot packs are safer, cleaner, and easier to use,
      we prefer warming by hot packs instead of hot water immersion before performing
      nerve conduction studies.

PMID- 24930945
TI  - Biomechanical mechanisms and centre of pressure trajectory during planned gait
      termination.
AB  - AIM: Although gait initiation has been extensively studied, gait termination has
      received less attention. In particular, the trajectory of the centre of pressure
      (CoP) during gait termination, as well as the trajectory's determinants, has not
      yet been described. The purpose of the present study was to characterize the
      kinetic components of planned gait termination (including the CoP trajectory)
      with respect to the various gait events and centre of mass speed and trajectory.
      METHODS: Thirty healthy subjects were asked to walk along a test track and stop
      on a force platform while an optoelectronic system recorded temporal and spatial
      parameters. A total of 90 trials were analysed. RESULTS: Subjects needed two
      steps to stop on the force platform. The CoP trajectory during gait termination
      was composed of three phases. During the first phase, the CoP moved forward under
      the stance foot, which was in contact with the ground. The ground reaction forces
      exerted a sagittal braking action. The second phase showed a lateral CoP shift
      and was correlated with braking; this may correspond to anticipatory postural
      adjustments for gait termination. The third and last phase might correspond to
      compensatory adjustments before the stance phase. CONCLUSIONS: CoP trajectory is
      more complex during gait termination than during gait initiation. Gait
      termination comprises several specific sequences in the gait-stance transition. A
      better understanding of the kinetic parameters in gait termination should enable
      us to identify which kinetic parameters could be considered as risk factors for
      falls.

PMID- 24930946
TI  - Should the concept of MCI be revised in order to improve detection of dementia?

PMID- 24930947
TI  - Monochromatic visible light "photoinitibitor": Janus-faced initiation and
      inhibition for storage of colored 3D images.
AB  - Controlling the kinetics and gelation of photopolymerization is a significant
      challenge in the fabrication of complex three-dimensional (3D) objects as is
      critical in numerous imaging, lithography, and additive manufacturing techniques.
      We propose a novel, visible light sensitive "photoinitibitor" which
      simultaneously generates two distinct radicals, each with their own unique
      purpose-one radical each for initiation and inhibition. The Janus-faced functions
      of this photoinitibitor delay gelation and dramatically amplify the gelation time
      difference between the constructive and destructive interference regions of the
      exposed holographic pattern. This approach enhances the photopolymerization
      induced phase separation of liquid crystal/acrylate resins and the formation of
      fine holographic polymer dispersed liquid crystal (HPDLC) gratings. Moreover, we
      construct colored 3D holographic images that are visually recognizable to the
      naked eye under white light. 

PMID- 24930949
TI  - Validation of the GreenLightTM Simulator and development of a training curriculum
      for photoselective vaporisation of the prostate.
AB  - OBJECTIVES: To assess face, content and construct validity, and feasibility and
      acceptability of the GreenLightTM Simulator as a training tool for photoselective
      vaporisation of the prostate (PVP), and to establish learning curves and develop
      an evidence-based training curriculum. SUBJECTS AND METHODS: This prospective,
      observational and comparative study, recruited novice (25 participants),
      intermediate (14) and expert-level urologists (seven) from the UK and Europe at
      the 28th European Association of Urological Surgeons Annual Meeting 2013. A group
      of novices (12 participants) performed 10 sessions of subtask training modules
      followed by a long operative case, whereas a second group (13) performed five
      sessions of a given case module. Intermediate and expert groups performed all
      training modules once, followed by one operative case. The outcome measures for
      learning curves and construct validity were time to task, coagulation time,
      vaporisation time, average sweep speed, average laser distance, blood loss,
      operative errors, and instrument cost. Face and content validity, feasibility and
      acceptability were addressed through a quantitative survey. RESULTS: Construct
      validity was demonstrated in two of five training modules (P = 0.038; P = 0.018)
      and in a considerable number of case metrics (P = 0.034). Learning curves were
      seen in all five training modules (P < 0.001) and significant reduction in case
      operative time (P < 0.001) and error (P = 0.017) were seen. An evidence-based
      training curriculum, to help trainees acquire transferable skills, was produced
      using the results. CONCLUSION: This study has shown the GreenLight Simulator to
      be a valid and useful training tool for PVP. It is hoped that by using the
      training curriculum for the GreenLight Simulator, novice trainees can acquire
      skills and knowledge to a predetermined level of proficiency.

PMID- 24930950
TI  - Guideline vs. practice in procollagen-3-aminopeptide monitoring.

PMID- 24930948
TI  - Differential affinities of MinD and MinE to anionic phospholipid influence Min
      patterning dynamics in vitro.
AB  - The E. coli Min system forms a cell-pole-to-cell-pole oscillator that positions
      the divisome at mid-cell. The MinD ATPase binds the membrane and recruits the
      cell division inhibitor MinC. MinE interacts with and releases MinD (and MinC)
      from the membrane. The chase of MinD by MinE creates the in vivo oscillator that
      maintains a low level of the division inhibitor at mid-cell. In vitro
      reconstitution and visualization of Min proteins on a supported lipid bilayer has
      provided significant advances in understanding Min patterns in vivo. Here we
      studied the effects of flow, lipid composition, and salt concentration on Min
      patterning. Flow and no-flow conditions both supported Min protein patterns with
      somewhat different characteristics. Without flow, MinD and MinE formed spiraling
      waves. MinD and, to a greater extent MinE, have stronger affinities for anionic
      phospholipid. MinD-independent binding of MinE to anionic lipid resulted in
      slower and narrower waves. MinE binding to the bilayer was also more susceptible
      to changes in ionic strength than MinD. We find that modulating protein diffusion
      with flow, or membrane binding affinities with changes in lipid composition or
      salt concentration, can differentially affect the retention time of MinD and
      MinE, leading to spatiotemporal changes in Min patterning. 

PMID- 24930951
TI  - Change in cannabis use in the general population: a longitudinal study on the
      impact on psychotic experiences.
AB  - OBJECTIVE: To prospectively assess the relationship between cannabis use and
      psychotic experiences over time. METHOD: In a longitudinal design, young adults
      aged 18-27years (N=705) gave online information on cannabis use and completed the
      Community Assessment of Psychic Experiences (CAPE). These measures were repeated
      after an interval ranging from six months to five years. RESULTS: A decrease in
      cannabis use was associated with a decrease in total psychotic experiences (beta=
      0.096, p=0.01) after adjustment for a range of potential confounders. An increase
      in cannabis use was associated with increased positive symptoms at follow-up
      (beta=0.07, p=0.02), but was not significantly associated with increases in
      Negative and Depression symptom scores, nor with the total number of psychotic
      experiences. CONCLUSION: In the first study to the association of change in
      cannabis use and psychotic experiences over time in the general population, we
      found an association between changes in cannabis use and changes in the frequency
      of psychotic experiences. While this does not prove a causal relationship between
      cannabis use and psychosis, our findings are consistent with studies suggesting
      that cessation of cannabis use may be beneficial in terms of reducing psychotic
      experiences.

PMID- 24930952
TI  - Mass spectrometry and redox proteomics: applications in disease.
AB  - Proteomics techniques are continuously being developed to further understanding
      of biology and disease. Many of the pathways that are relevant to disease
      mechanisms rely on the identification of post-translational modifications (PTMs)
      such as phosphorylation, acetylation, and glycosylation. Much attention has also
      been focused on oxidative PTMs which include protein carbonyls, protein
      nitration, and the incorporation of fatty acids and advanced glycation products
      to amino acid side chains, amongst others. The introduction of these PTMs in the
      cell can occur due to the attack of reactive oxygen and nitrogen species (ROS and
      RNS, respectively) on proteins. ROS and RNS can be present as a result of normal
      metabolic processes as well as external factors such as UV radiation, disease,
      and environmental toxins. The imbalance of ROS and RNS with antioxidant cellular
      defenses leads to a state of oxidative stress, which has been implicated in many
      diseases. Redox proteomics techniques have been used to characterize oxidative
      PTMs that result as a part of normal cell signaling processes as well as
      oxidative stress conditions. This review highlights many of the redox proteomics
      techniques which are currently available for several oxidative PTMs and brings to
      the reader's attention the application of redox proteomics for understanding
      disease pathogenesis in neurodegenerative disorders and others such as cancer,
      kidney, and heart diseases.

PMID- 24930954
TI  - Knockdown of miR-210 decreases hypoxic glioma stem cells stemness and
      radioresistance.
AB  - Glioma contains abundant hypoxic regions which provide niches to promote the
      maintenance and expansion of glioma stem cells (GSCs), which are resistant to
      conventional therapies and responsible for recurrence. Given the fact that miR
      210 plays a vital role in cellular adaption to hypoxia and in stem cell survival
      and stemness maintenance, strategies correcting the aberrantly expressed miR-210
      might open up a new therapeutic avenue to hypoxia GSCs. In the present study, to
      explore the possibility of miR-210 as an effective therapeutic target to hypoxic
      GSCs, we employed a lentiviral-mediated anti-sense miR-210 gene transfer
      technique to knockdown miR-210 expression and analyze phenotypic changes in
      hypoxic U87s and SHG44s cells. We found that hypoxia led to an increased HIF
      2alpha mRNA expression and miR-210 expression in GSCs. Knockdown of miR-210
      decreased neurosphere formation capacity, stem cell marker expression and cell
      viability, and induced differentiation and G0/G1 arrest in hypoxic GSCs by
      partially rescued Myc antagonist (MNT) protein expression. Knockdown of MNT could
      reverse the gene expression changes and the growth inhibition resulting from
      knockdown of miR-210 in hypoxic GSCs. Moreover, knockdown of miR-210 led to
      increased apoptotic rate and Caspase-3/7 activity and decreased invasive
      capacity, reactive oxygen species (ROS) and lactate production and
      radioresistance in hypoxic GSCs. These findings suggest that miR-210 might be a
      potential therapeutic target to eliminate GSCs located in hypoxic niches. 

PMID- 24930955
TI  - Persistence of nosocomial bacteria on 2 biocidal fabrics based on silver under
      conditions of high relative humidity.
AB  - BACKGROUND: The survival of pathogenic microorganism on fabrics in the health
      care environment has a important role in nosocomial infections. The use of
      biocidal fabrics and surfaces could reduce the prevalence of the microorganisms
      in the hospital environment. METHODS: In this study, the persistence of
      nosocomial bacteria on 2 fabrics containing biocidal fibers (BF) in the long term
      following desiccation and subsequent storage was examined at 40% and 90% relative
      humidity (RH). RESULTS: Very few strains survived more than 7 days at 40% RH on
      fabrics containing 67% BF, and only strains of Acinetobacter baumanii and
      Pseudomonas aeruginosa survived on fabric containing 100% BF. None of the strains
      tested survived 14 days on the 2 fabrics, 67% or 100% BF, under these
      environmental conditions. In contrast, at higher RH (~90%), most of the strains
      tested showed prolonged survival on both fabrics, and all strains of Klebsiella
      pneumoniae, Enterobacter aerogenes, and A baumannii survived for more than 14
      days; however, in a Petri dish, most of the microorganisms tested showed a higher
      survival even at 28 days. The gram-positive cocci and A baumannii were the most
      persistent bacteria on the Petri dish. CONCLUSIONS: This study emphasizes the
      effect of RH on the survival of nosocomial bacteria on 2 commercially available
      fabrics containing biocide. Evidence of the clinical efficacy of these BF
      containing fabrics is lacking.

PMID- 24930956
TI  - Validation of nosocomial infection in neonatology: a new method for standardized
      surveillance.
AB  - BACKGROUND: Nosocomial infections (NIs) are a leading cause of mortality and
      morbidity in premature infants. We present a new method for detecting and
      confirming NIs in a neonatal intensive care unit. METHODS: Newborns with birth
      weight < 1,500 g or gestational age (GA) < 33 weeks were included prospectively
      over 2 years in a single-center tertiary neonatal intensive care unit. The
      computerized physician order entry system (CPOE) generated alerts when
      antibiotics were prescribed for at least 5 consecutive days and these cases were
      reviewed by an expert group following international recommendations. RESULTS:
      Four hundred sixty-one neonates were included, with a mean GA of 30 weeks (range,
      26-32 weeks) and mean birth weight 1,270 g (range, 950-1600 g). The CPOE flagged
      158 cases of potential NI, 85.1% of which were classified as true NI and 14.9% of
      which were false positive. Incidence and device-associated nosocomial bloodstream
      infection rates were 21.9% and 10.8 per 1,000 central venous catheter days,
      respectively. GA <= 28 weeks (odds ratio, 2.18; 95% confidence interval, 1.2-4)
      and > 7 central venous catheter days (odds ratio, 1.47; 95% confidence interval,
      1.3-1.7) were independently associated with the risk of nosocomial bloodstream
      infection. CONCLUSION: Combining CPOE and interdisciplinary review may improve
      the accuracy of NI recording in a neonatal intensive care unit.

PMID- 24930957
TI  - Effects of light quality on the accumulation of phytochemicals in vegetables
      produced in controlled environments: a review.
AB  - Phytochemicals in vegetables are important for human health, and their
      biosynthesis, metabolism and accumulation are affected by environmental factors.
      Light condition (light quality, light intensity and photoperiod) is one of the
      most important environmental variables in regulating vegetable growth,
      development and phytochemical accumulation, particularly for vegetables produced
      in controlled environments. With the development of light-emitting diode (LED)
      technology, the regulation of light environments has become increasingly feasible
      for the provision of ideal light quality, intensity and photoperiod for protected
      facilities. In this review, the effects of light quality regulation on
      phytochemical accumulation in vegetables produced in controlled environments are
      identified, highlighting the research progress and advantages of LED technology
      as a light environment regulation tool for modifying phytochemical accumulation
      in vegetables.

PMID- 24930958
TI  - Three-dimensional thin film for lithium-ion batteries and supercapacitors.
AB  - Three-dimensional heterogeneously nanostructured thin-film electrodes were
      fabricated by using Ta2O5 nanotubes as a framework to support carbon-onion-coated
      Fe2O3 nanoparticles along the surface of the nanotubes. Carbon onion layers
      function as microelectrodes to separate the two different metal oxides and form a
      nanoscale 3-D sandwich structure. In this way, space-charge layers were formed at
      the phase boundaries, and it provides additional energy storage by charge
      separation. These 3-D nanostructured thin films deliver both excellent Li-ion
      battery properties (stabilized at 800 mAh cm(-3)) and supercapacitor (up to 18.2
      mF cm(-2)) performance owing to the synergistic effects of the heterogeneous
      structure. Thus, Li-ion batteries and supercapacitors are successfully assembled
      into the same electrode, which is promising for next generation hybrid energy
      storage and delivery devices.

PMID- 24930953
TI  - Biochemical and cellular analysis of human variants of the DYT1 dystonia protein,
      TorsinA/TOR1A.
AB  - Early-onset dystonia is associated with the deletion of one of a pair of glutamic
      acid residues (c.904_906delGAG/c.907_909delGAG; p.Glu302del/Glu303del; DeltaE
      302/303) near the carboxyl-terminus of torsinA, a member of the AAA(+) protein
      family that localizes to the endoplasmic reticulum lumen and nuclear envelope.
      This deletion commonly underlies early-onset DYT1 dystonia. While the role of the
      disease-causing mutation, torsinADeltaE, has been established through genetic
      association studies, it is much less clear whether other rare human variants of
      torsinA are pathogenic. Two missense variations have been described in single
      patients: R288Q (c.863G>A; p.Arg288Gln; R288Q) identified in a patient with onset
      of severe generalized dystonia and myoclonus since infancy and F205I (c.613T>A,
      p.Phe205Ile; F205I) in a psychiatric patient with late-onset focal dystonia. In
      this study, we have undertaken a series of analyses comparing the biochemical and
      cellular effects of these rare variants to torsinADeltaE and wild-type (wt)
      torsinA to reveal whether there are common dysfunctional features. The results
      revealed that the variants, R288Q and F205I, are more similar in their properties
      to torsinADeltaE protein than to torsinAwt. These findings provide functional
      evidence for the potential pathogenic nature of these rare sequence variants in
      the TOR1A gene, thus implicating these pathologies in the development of
      dystonia. 

PMID- 24930959
TI  - Altered burst swimming in rainbow trout Oncorhynchus mykiss exposed to natural
      and synthetic oestrogens.
AB  - Juvenile rainbow trout Oncorhynchus mykiss were exposed to two concentrations
      each of 17beta-oestradiol (E2; natural oestrogen hormone) or 17alpha-ethinyl
      oestradiol (EE2; a potent synthetic oestrogen hormone) to evaluate their
      potential effects on burst-swimming performance. In each of six successive burst
      swimming assays, burst-swimming speed (Uburst ) was lower in fish exposed to 0.5
      and 1 ug l(-1) E2 and EE2 for four days compared with control fish. A practice
      swim (2 days prior to exposure initiation) in control fish elevated initial
      Uburst values, but this training effect was not evident in the 1 ug l(-1) EE2
      exposed fish. Several potential oestrogen-mediated mechanisms for Uburst
      reductions were investigated, including effects on metabolic products,
      osmoregulation and blood oxygen-carrying capacity. Prior to burst-swimming
      trials, fish exposed to E2 and EE2 for 4 days had significantly reduced
      erythrocyte numbers and lower plasma glucose concentrations. After six repeated
      burst-swimming trials, plasma glucose, lactate and creatinine concentrations were
      not significantly different among treatment groups; however, plasma Cl(-)
      concentrations were significantly reduced in E2- and EE2-treated fish. In
      summary, E2 and EE2 exposure altered oxygen-carrying capacity ([erythrocytes])
      and an osmoregulatory-related variable ([Cl(-) ]), effects that may underlie
      reductions in burst-swimming speed, which will have implications for fish
      performance in the wild.

PMID- 24930960
TI  - Objective assessment of endoscopy assisted adenoidectomy.
AB  - OBJECTIVES: To objectively assess the effectiveness of endoscopy assisted
      adenoidectomy utilizing adenoid tissue volume measurement and to set some
      parameters for which patients are more legible to this procedure. METHODS: Forty
      three patients for whom adenoidectomy was conventionally done using adenoid
      curettes. Surgeon's satisfaction for adenoid removal after curettage and digital
      palpation was reported. The volume of removed adenoidal tissue was measured. The
      remaining adenoid tissue, if any, was removed transnasally guided by endoscope.
      Residual adenoid volume was also was measured. The data was tabulated and
      statistically analyzed. RESULTS: The volume of adenoid removed by curettage
      ranged from 1 to 3.6 ml with a mean of 2.45 ml. The volume of residual adenoid
      removed by endoscopy after curettage ranged from 0 to 2.9 ml (mean: 0.67 +/- 0.58
      ml). The volume of residual adenoid after blind curettage was found to have
      statistically significant relation to older age of patients, preoperative larger
      adenoid by X-ray and Surgeon's dissatisfaction about the completeness of removal
      after curettage. CONCLUSION: Conventional curettage adenoidectomy misses a
      substantial volume of adenoid tissue. Endoscopy-assisted adenoidectomy is
      significantly recommended in children age  >10 years, dissatisfied surgeon after
      curettage and palpation, and grade 3 adenoid enlargement on X-ray.

PMID- 24930961
TI  - Effects of the venom of the spider Ornithoctonus hainana on neonatal rat
      ventricular myocytes cellular and ionic electrophysiology.
AB  - Cardiac ion channels are membrane-spanning proteins that allow the passive
      movement of ions across the cell membrane along its electrochemical gradient,
      which regulates the resting membrane potential as well as the shape and duration
      of the cardiac action potential. Additionally, they have been recognized as
      potential targets for the actions of neurotransmitters, hormones and drugs of
      cardiac diseases. Spider venoms contain high abundant of toxins that target
      diverse ion channels and have been considered as a potential resource of new
      constituents with specific pharmacological properties. However, few peptides from
      spider venoms were detected as cardiac channel antagonists. In order to explore
      the effects of the venom of Ornithoctonus hainana on the action potential and
      ionic currents of neonatal rat ventricular myocytes (NRVMs), whole cell patch
      clamp technique was used to record action potential duration (APD), sodium
      current (INa), L calcium current (ICaL), rapidly activating and inactivating
      transient outward currents (Ito1), rapid (IKr) and slow (IKs) components of the
      delayed rectifier currents and the inward rectifier currents (IK1). Our results
      showed that 100 MUg/mL venom obviously prolonged APDs. Significantly, the venom
      could inhibit INa and ICaL effectively, while no evident inhibitory effects on
      cardiac K(+) channels (Ito1, Iks, Ikr and Ik1) were observed, suggesting that the
      venom represented a multifaceted pharmacological profile. The effect of venom on
      Na(+) and Ca(2+) currents of ventricular myocytes revealed that the hainan venom
      as a rich resource of cardiac channel antagonists might be valuable tools for the
      investigation of both channels and drug development. 

PMID- 24930962
TI  - Associations between prescription opioid use and sleep impairment among veterans
      with chronic pain.
AB  - OBJECTIVE: Chronic pain is associated with impairments in sleep; however, the
      relationship between prescription opioid status and sleep is unclear. The primary
      aim of this study was to examine differences in self-reported sleep quality
      between groups of patients who varied based on chronic pain and prescription
      opioid status. DESIGN: This is a cross-sectional study with retrospective review
      of patient medical records. SETTING: The study was performed in a single VA
      medical center located in the Pacific Northwest. SUBJECTS: Participants with
      chronic pain and a current prescription for opioid medications (N=72), chronic
      pain and no opioid prescription (N=104), or who did not report current chronic
      pain or opioid prescription (N=91) were included. METHODS: All participants
      completed self-report questionnaires assessing demographic characteristics, sleep
      parameters, pain-related variables, and psychiatric symptoms. Data on
      prescription opioid use were extracted from patients' medical records. RESULTS:
      In unadjusted analyses, patients with chronic pain who were prescribed opioids
      were more likely to have sleep apnea diagnoses in their medical record and
      reported more impairment on sleep global score and across four sleep parameter
      subscales (subjective sleep quality, sleep latency, sleep disturbance, and use of
      sleeping medications). In linear regression analyses controlling for demographic
      and clinical covariates, prescription opioid status was associated with sleep
      latency, and opioid dose was significantly associated with sleep latency and
      sleep global score. CONCLUSIONS: Prescription opioid status and dose were
      associated with impairment in self-reported sleep. For patients with chronic
      pain, consideration should be given to use of nonpharmacological interventions to
      improve sleep.

PMID- 24930964
TI  - Fascin plays a role in stress fiber organization and focal adhesion disassembly.
AB  - Migrating cells nucleate focal adhesions (FAs) at the cell front and disassemble
      them at the rear to allow cell translocation. FAs are made of a multiprotein
      complex, the adhesome, which connects integrins to stress fibers made of mixed
      polarity actin filaments [1-5]. Myosin II-driven contraction of stress fibers
      generates tensile forces that promote adhesion growth [6-9]. However, tension
      must be tightly controlled, because if released, FAs disassemble [3, 10-12].
      Conversely, excess tension can cause abrupt cell detachment resulting in the loss
      of a major part of the adhesion [9, 12]. Thus, both adhesion growth and
      disassembly depend on tensile forces generated by stress fiber contraction, but
      how this contractility is regulated remains unclear. Here, we show that the actin
      bundling protein fascin crosslinks the actin filaments into parallel bundles at
      the stress fibers' termini. Fascin prevents myosin II entry at this region and
      inhibits its activity in vitro. In fascin-depleted cells, polymerization of actin
      filaments at the stress fiber termini is slower, the actin cytoskeleton is
      reorganized into thicker stress fibers with a higher number of myosin II
      molecules, FAs are larger and less dynamic, and consequently, traction forces
      that cells exert on their substrate are larger. We also show that fascin
      dissociation from stress fibers is required to allow their severing by cofilin,
      leading to efficient disassembly of FAs.

PMID- 24930963
TI  - Activation of the APC/C ubiquitin ligase by enhanced E2 efficiency.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a protein-ubiquitin ligase
      (E3) that initiates the final events of mitosis by catalyzing the ubiquitination
      and proteasomal destruction of securin, cyclins, and other substrates [1, 2].
      Like other members of the RING family of E3s [3, 4], the APC/C catalyzes direct
      ubiquitin transfer from an E2-ubiquitin conjugate (E2-Ub) to lysine residues on
      the protein substrate. The APC/C is activated at specific cell-cycle stages by
      association with an activator subunit, Cdc20 or Cdh1, which provides binding
      sites for specific substrate sequence motifs, or degrons. Activator might also
      stimulate catalytic activity [5, 6], but the underlying mechanisms are not known.
      Here, we dissected activator function using an artificial fusion substrate in
      which the N-terminal region of securin was linked to an APC/C core subunit. This
      fusion substrate bound tightly to the APC/C and was ubiquitinated at a low rate
      in the absence of activator. Ubiquitination of this substrate was stimulated by
      activator, due primarily to a dramatic stimulation of E2 sensitivity (Km) and
      catalytic rate (kcat), which together resulted in a 670-fold stimulation of
      kcat/Km. Thus, activator is not simply a substrate adaptor, but also enhances
      catalysis by promoting a more efficient interaction with the E2-Ub.
      Interestingly, full E2 stimulation required activator interaction with degron
      motifs on the substrate. We conclude that formation of a complete APC/C-activator
      substrate complex leads to a major enhancement of E2 efficiency, providing an
      unusual substrate-assisted catalytic mechanism that limits efficient ubiquitin
      transfer to specific substrates.

PMID- 24930965
TI  - Assembling the protein architecture of the budding yeast kinetochore-microtubule
      attachment using FRET.
AB  - BACKGROUND: The kinetochore is a multiprotein machine that couples chromosome
      movement to microtubule (MT) polymerization and depolymerization. It uses
      numerous copies of at least three MT-binding proteins to generate bidirectional
      movement. The nanoscale organization of these proteins within the kinetochore
      plays an important role in shaping the mechanisms that drive persistent,
      bidirectional movement of the kinetochore. RESULTS: We used fluorescence
      resonance energy transfer (FRET) between genetically encoded fluorescent proteins
      fused to kinetochore subunits to reconstruct the nanoscale organization of the
      budding yeast kinetochore. We performed >60 FRET and high-resolution
      colocalization measurements involving the essential MT-binding kinetochore
      components: Ndc80, Dam1, Spc105, and Stu2. These measurements reveal that
      neighboring Ndc80 complexes within the kinetochore are narrowly distributed along
      the length of the MT. Dam1 complex molecules are concentrated near the MT-binding
      domains of Ndc80. Stu2 localizes in high abundance within a narrowly defined
      territory within the kinetochore centered ~20 nm on the centromeric side of the
      Dam1 complex. CONCLUSIONS: Our data show that the MT attachment site of the
      budding yeast kinetochore is well organized. Ndc80, Dam1, and Stu2 are all
      narrowly distributed about their average positions along the kinetochore-MT axis.
      The relative organization of these components, their narrow distributions, and
      their known MT-binding properties together elucidate how their combined actions
      generate persistent, bidirectional kinetochore movement coupled to MT
      polymerization and depolymerization.

PMID- 24930966
TI  - Drosophila lipid droplets buffer the H2Av supply to protect early embryonic
      development.
AB  - Assembly of DNA into chromatin requires a delicate balancing act, as both dearth
      and excess of histones severely disrupt chromatin function [1-3]. In particular,
      cells need to carefully control histone stoichiometry: if different types of
      histones are incorporated into chromatin in an imbalanced manner, it can lead to
      altered gene expression, mitotic errors, and death [4-6]. Both the balance
      between individual core histones and the balance between core histones and
      histone variants are critical [5, 7]. Here, we find that in early Drosophila
      embryos, histone balance in the nuclei is regulated by lipid droplets,
      cytoplasmic fat-storage organelles [8]. Lipid droplets were previously known to
      function in long-term histone storage: newly laid embryos contain large amounts
      of excess histones generated during oogenesis [9], and the maternal supplies of
      core histone H2A and the histone variant H2Av are anchored to lipid droplets via
      the novel protein Jabba [3]. We find that in these embryos, synthesis of new H2A
      and H2Av is imbalanced, and that newly produced H2Av can be recruited to lipid
      droplets. When droplet sequestration is disrupted by mutating Jabba, embryos
      display an elevated H2Av/H2A ratio in nuclei as well as mitotic defects, reduced
      viability, and hypersensitivity to H2Av overexpression. We propose that in
      Drosophila embryos, lipid droplets serve as a histone buffer, not only storing
      maternal histones to support the early cell cycles but also transiently
      sequestering H2Av produced in excess and thus ensuring proper histone balance in
      the nucleus.

PMID- 24930967
TI  - Enantioseparation of benzofurys and other novel psychoactive compounds by CE and
      sulfobutylether beta-cyclodextrin as chiral selector added to the BGE.
AB  - The illicit drug market of psychoactive substances for human abuse is
      continuously expanding and developing. Besides already known substance classes
      like cathinones, amphetamines or synthetic cannabinoids, further derivatives such
      as benzofurys, thiophenes, and structural analogues of methylphenidate entered
      the global market recently. As many of these new compounds contain a stereogenic
      centre it is supposed that their isomers may differ in their pharmacological
      effects as it is the case with amphetamines or several chiral active
      pharmaceutical ingredients, for instance. In the course of this study, a method
      for the chiral separation of a set of 16 recreational drugs by CE was developed.
      The aim was to separate the analytes into their enantiomers at equal conditions
      within short time. Sulfobutylether beta-cyclodextrin served as chiral selector in
      an aqueous ammonium acetate solution containing ACN. For method optimization,
      methedrone and ethylphenidate were used as model compounds to find the
      appropriate concentration of chiral selector. Moreover, the influence of the pH
      value on enantioseparation was tested. Fourteen or 16 mM sulfobutylether beta
      cyclodextrin, 50 mM ammonium acetate solution (pH 4.5) with 10% ACN were found to
      be optimal for enantioseparation of seven benzofurys, four cathinones, two
      diphenidines, ethylphenidate, methiopropamine, and thiothinone. Most of them were
      baseline resolved at migration times below 25 min. 

PMID- 24930968
TI  - Folded small molecule manipulation of islet amyloid polypeptide.
AB  - Islet amyloid polypeptide (IAPP) is a hormone cosecreted with insulin by
      pancreatic beta cells. Upon contact with lipid bilayers, it is stabilized into a
      heterogeneous ensemble of structural states. These processes are associated with
      gains of function, including catalysis of beta sheet-rich amyloid formation, cell
      membrane penetration, loss of membrane integrity, and cytotoxicity. These
      contribute to the dysfunction of beta cells, a central component in the pathology
      and treatment of diabetes. To gain mechanistic insight into these phenomena, a
      related series of substituted oligoquinolines were designed. These inhibitors are
      unique in that they have the capacity to affect both solution- and phospholipid
      bilayer-catalyzed IAPP self-assembly. Importantly, we show that this activity is
      associated with the oligoquinoline's capacity to irreversibly adopt a noncovalent
      fold. This suggests that compact foldamer scaffolds, such as oligoquinoline, are
      an important paradigm for conformational manipulation of disordered protein
      state. 

PMID- 24930969
TI  - Enzyme inhibition by hydroamination: design and mechanism of a hybrid carmaphycin
      syringolin enone proteasome inhibitor.
AB  - Hydroamination reactions involving the addition of an amine to an inactivated
      alkene are entropically prohibited and require strong chemical catalysts. While
      this synthetic process is efficient at generating substituted amines, there is no
      equivalent in small molecule-mediated enzyme inhibition. We report an unusual
      mechanism of proteasome inhibition that involves a hydroamination reaction of
      alkene derivatives of the epoxyketone natural product carmaphycin. We show that
      the carmaphycin enone first forms a hemiketal intermediate with the catalytic
      Thr1 residue of the proteasome before cyclization by an unanticipated
      intramolecular alkene hydroamination reaction, resulting in a stable six-membered
      morpholine ring. The carmaphycin enone electrophile, which does not undergo a 1,4
      Michael addition as previously observed with vinyl sulfone and alpha,beta
      unsaturated amide-based inhibitors, is partially reversible and gives insight
      into the design of proteasome inhibitors for cancer chemotherapy. 

PMID- 24930970
TI  - The glucose transporter Glut1 is selectively essential for CD4 T cell activation
      and effector function.
AB  - CD4 T cell activation leads to proliferation and differentiation into effector
      (Teff) or regulatory (Treg) cells that mediate or control immunity. While each
      subset prefers distinct glycolytic or oxidative metabolic programs in vitro,
      requirements and mechanisms that control T cell glucose uptake and metabolism in
      vivo are uncertain. Despite expression of multiple glucose transporters, Glut1
      deficiency selectively impaired metabolism and function of thymocytes and Teff.
      Resting T cells were normal until activated, when Glut1 deficiency prevented
      increased glucose uptake and glycolysis, growth, proliferation, and decreased
      Teff survival and differentiation. Importantly, Glut1 deficiency decreased Teff
      expansion and the ability to induce inflammatory disease in vivo. Treg cells, in
      contrast, were enriched in vivo and appeared functionally unaffected and able to
      suppress Teff, irrespective of Glut1 expression. These data show a selective in
      vivo requirement for Glut1 in metabolic reprogramming of CD4 T cell activation
      and Teff expansion and survival.

PMID- 24930971
TI  - Mitochondrial proteostasis in the control of aging and longevity.
AB  - Mitochondria play a central role in the aging process. Studies in model organisms
      have started to integrate mitochondrial effects on aging with the maintenance of
      protein homeostasis. These findings center on the mitochondrial unfolded protein
      response (UPR(mt)), which has been implicated in lifespan extension in worms,
      flies, and mice, suggesting a conserved role in the long-term maintenance of
      cellular homeostasis. Here, we review current knowledge of the UPR(mt) and
      discuss its integration with cellular pathways known to regulate lifespan. We
      highlight how insight into the UPR(mt) is revolutionizing our understanding of
      mitochondrial lifespan extension and of the aging process. 

PMID- 24930972
TI  - Lipin-1 regulates autophagy clearance and intersects with statin drug effects in
      skeletal muscle.
AB  - LPIN1 encodes lipin-1, a phosphatidic acid phosphatase (PAP) enzyme that
      catalyzes the dephosphorylation of phosphatidic acid to form diacylglycerol.
      Homozygous LPIN1 gene mutations cause severe rhabdomyolysis, and heterozygous
      LPIN1 missense mutations may promote statin-induced myopathy. We demonstrate that
      lipin-1-related myopathy in the mouse is associated with a blockade in autophagic
      flux and accumulation of aberrant mitochondria. Lipin-1 PAP activity is required
      for maturation of autolysosomes, through its activation of the protein kinase D
      (PKD)-Vps34 phosphatidylinositol 3-kinase signaling cascade. Statin treatment
      also reduces PKD activation and autophagic flux, which are compounded by
      diminished mammalian target of rapamycin (mTOR) abundance in lipin-1
      haploinsufficent and -deficient muscle. Lipin-1 restoration in skeletal muscle
      prevents myonecrosis and statin toxicity in vivo, and activated PKD rescues
      autophagic flux in lipin-1-deficient cells. Our findings identify lipin-1 PAP
      activity as a component of the macroautophagy pathway and define the basis for
      lipin-1-related myopathies. 

PMID- 24930974
TI  - Outcomes after arterial endovascular procedures performed in patients with an
      elevated international normalized ratio.
AB  - BACKGROUND: Patients treated with anticoagulants frequently require urgent
      vascular procedures and elevated prothrombin time/international normalized ratio
      (INR) is traditionally thought to increase access site bleeding complications
      after sheath removal. We aimed to determine the safety of percutaneous arterial
      procedures on patients with a high INR in the era of modern ultrasound-guided
      access and closure device use. METHODS: Patients undergoing arterial endovascular
      procedures at a single institution between October 2010 and November 2012 were
      reviewed (n = 1,333). We retrospectively analyzed all patients with an INR > 1.5.
      Venous procedures, lysis checks, and cases with no documented INR within 24 hr
      were excluded. Sixty-five patients with 91 punctures were identified. A
      comparison group was then generated from the last 91 patients intervened on with
      INR < 1.6. Demographics, intraoperative data, and postoperative complications
      were compared. RESULTS: The demographics were similar. More Coumadin use and
      higher INR were found in the study group (71/91 and 0/91, P = 0.001; 2.3 and 1.1
      sec, P = 0.001, respectively), but there was more antiplatelet use in the control
      group (68/91 and 51/91, P = 0.01). Intraoperatively, the sheath sizes, protamine
      use, closure device use, ultrasound guidance, brachial access, and procedure
      types were not statistically different. Sheath sizes ranged from 4 to 22F in the
      study group and 4 to 20F in the control group. Paradoxically, heparin was
      administered more frequently in the study group (64/91 and 50/91, P = 0.046).
      Bleeding complications occurred more commonly in the study group (3/91 and 1/91,
      P = 0.62), but this failed to reach significance and the overall complication
      rate in both groups was low. CONCLUSIONS: Endovascular procedures may be
      performed safely with a low risk of bleeding complications in patients with an
      elevated INR. Ultrasound guidance and closure device use may allow these cases to
      be performed safely, but a larger series may be needed to confirm this.

PMID- 24930973
TI  - Adipocyte inflammation is essential for healthy adipose tissue expansion and
      remodeling.
AB  - Chronic inflammation constitutes an important link between obesity and its
      pathophysiological sequelae. In contrast to the belief that inflammatory signals
      exert a fundamentally negative impact on metabolism, we show that proinflammatory
      signaling in the adipocyte is in fact required for proper adipose tissue
      remodeling and expansion. Three mouse models with an adipose tissue-specific
      reduction in proinflammatory potential were generated that display a reduced
      capacity for adipogenesis in vivo, while the differentiation potential is
      unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral
      adipose tissue is prominently affected. This is associated with decreased
      intestinal barrier function, increased hepatic steatosis, and metabolic
      dysfunction. An impaired local proinflammatory response in the adipocyte leads to
      increased ectopic lipid accumulation, glucose intolerance, and systemic
      inflammation. Adipose tissue inflammation is therefore an adaptive response that
      enables safe storage of excess nutrients and contributes to a visceral depot
      barrier that effectively filters gut-derived endotoxin.

PMID- 24930975
TI  - Influence of the hostile neck on restenosis after carotid stenting.
AB  - BACKGROUND: Carotid artery stenting (CAS) for carotid stenosis is favored over
      carotid endarterectomy (CEA) in patients with a hostile neck from prior CEA or
      cervical irradiation (XRT). However, the restenosis rate after CAS in patients
      with hostile necks is variable in the literature. The objective of this study was
      to quantify differences in the in-stent restenosis (ISR)/occlusion and
      reintervention rates after CAS in patients with and without a hostile neck. Here
      we hypothesize that patients with hostile necks have an increased ISR, and that
      this increase may add morbidity to these patients. MATERIALS AND METHODS: All
      patients undergoing CAS from 2007 to 2013 for carotid artery stenosis with follow
      up imaging at our institution were queried from our carotid database (n = 236).
      Patients with hostile necks, including both CAS after prior CEA (n = 65) and
      prior XRT (n = 37), were compared with patients who underwent CAS for other
      reasons including both anatomical (n = 46) and medical comorbidities (n = 88).
      The primary end points were ISR, repeat intervention, and stent occlusion.
      Secondary end points of the study were stroke/myocardial infarction (MI)/death at
      30 days, perioperative cardiovascular accident, transient ischemic attack, MI,
      groin access complications, hyperperfusion syndrome, and periprocedural
      hypotension or bradycardia. RESULTS: Despite the hostile neck cohort being
      younger and having lower incidence of chronic obstructive pulmonary disease,
      coronary artery disease, and renal insufficiency, they had a greater incidence of
      ISR (11% vs. 4%; P = .03) and required more reinterventions (8% vs. 2%; P = .04).
      Stent occlusion and periprocedural morbidity/mortality were not different between
      groups. CONCLUSIONS: Patients with hostile necks have increased risk of
      restenosis and need for reinterventions after CAS compared with patients without
      a hostile neck. However, they do not appear to have higher rates of stent
      occlusion or per-procedural events.

PMID- 24930976
TI  - Case report: a new hybrid surgical approach for treating mosaic pattern secondary
      lymphedema in the lower extremities.
AB  - Two of the most common surgical lymph reconstructive interventions for the
      treatment of secondary lymphedema today are lymphaticovenous anastomosis (LVA)
      and lymph node transplant. However, neither of these approaches has proven enough
      evidence to be considered as an effective treatment measure. In this case report,
      we will introduce a "hybrid method" where combinations of these two conventional
      methods are used in treating a 52-year-old female patient who displays a mosaic
      pattern of aggravating secondary lymphedema. Preoperative indocyanine green
      lymphography assessment was used to identify the different stages of lymphedema
      within the symptomatic limbs. The application of the hybrid method has resulted
      in a faster improvement in limb circumference and tissue tenderness compared with
      when only LVA is performed and has resulted in successful recovery from
      lymphedema in our case. The hybrid method allows surgeons to select the most
      appropriate surgical approach for each region displaying a different severity
      staging of lymphedema, establishing a new order-made remedy for chronic secondary
      lymphedema patients. 

PMID- 24930977
TI  - Pancreaticoduodenal artery aneurysms secondary to median arcuate ligament
      syndrome may not need celiac artery revascularization or ligament release.
AB  - INTRODUCTION: Median arcuate ligament syndrome (MALS) is a rare disorder defined
      by compression and narrowing of the celiac artery by the median arcuate ligament.
      The increased blood flow through the pancreaticoduodenal arcade can lead to the
      aneurysmal formation within the vessel. We report 3 cases of pancreaticoduodenal
      arterial aneurysms (PDAAs) in patients with MALS whose aneurysms were occluded,
      but celiac artery revascularization was not performed. METHODS: Case 1:
      Asymptomatic 61-year-old female with no past medical history was referred to
      vascular surgery for evaluation of a PDAA incidentally found on computed
      tomography (CT) scan. The patient was taken for laparoscopic division of the
      median arcuate ligament; however, the release was incomplete. This was followed
      by endovascular coil embolization of the PDAA without celiac revascularization.
      The patient tolerated the procedure well with no complications and the 1-year
      follow-up shows no signs of aneurysm recurrence. Case 2: A 61-year-old male found
      to have an incidental PDAA on CT scan. The patient was taken for coil
      embolization without median arcuate ligament release. At the 1-year follow-up,
      the patient continues to be asymptomatic with no recurrence. Case 3: A 56-year
      old male presented with a ruptured PDAA. He was taken immediately for coil
      embolization of the ruptured aneurysm. Postoperatively, the patient was
      identified to have MALS on CT scan. Because of his asymptomatic history and
      benign physical examination before the rupture, he was not taken for a ligament
      release or celiac revascularization. He continues to be asymptomatic at his
      follow-up. RESULTS: PDAAs secondary to MALS are very rare and most commonly
      diagnosed at the time of rupture, which has a mortality rate that reaches
      approximately 30%, making early identification and treatment necessary. Standard
      treatment would include exclusion of the aneurysm followed by celiac
      revascularization; however, these 3 cases identify an alternative approach to the
      standard treatment. CONCLUSION: Celiac revascularization may not be necessary in
      the asymptomatic patient with a PDAA who has close follow-up and serial imaging.

PMID- 24930978
TI  - Mycotic popliteal aneurysm rupture secondary to Campylobacter fetus.
AB  - BACKGROUND: Mycotic aneurysms of the popliteal artery are uncommon. Popliteal
      aneurysms rarely rupture. The authors present the second reported case of
      popliteal artery rupture as a result of Campylobacter fetus infection. This
      report confirms the arterial destructive potential of C. fetus infection in a
      peripheral artery. METHODS: An 85-year-old male who had previously undergone
      endovascular abdominal aortic aneurysm repair in 2007 presented with positive
      blood cultures for C. fetus. No endocarditis was detected. No periprosthetic
      fluid to suggest aortic endograft infection was present. During hospitalization
      for sepsis, he developed acute right knee pain and swelling. A 5.2-cm popliteal
      aneurysm, with contained rupture, was found on ultrasound and confirmed by
      computed tomography and angiography. Recommendations for treatment and a
      literature review are provided. RESULTS: This patient was successfully managed
      with total excision of the aneurysm via a posterior approach with reconstruction
      through a medial approach using autologous saphenous vein bypass. Culture
      directed antibiotic therapy (6 weeks of intravenous ertapenem) to eradicate the
      pathogen completed the therapy. The patient is doing well at 18- month follow-up.
      CONCLUSIONS: Mycotic popliteal aneurysm associated with C. fetus is a rare but
      potentially fatal condition. Isolating C. fetus should alert the surgeon to the
      peripheral arterial destructive potential of this pathogen, as manifested by
      acute rupture in this patient. Traditional resection through a posterior approach
      and revascularization through noncontaminated tissue with culture-directed
      therapy are the treatments of choice.

PMID- 24930979
TI  - Current results of a combined endovascular and open approach for the treatment of
      aortoesophageal and aortobronchial fistulae.
AB  - BACKGROUND: Aortoesophageal (AEF) and aortobronchial (ABF) fistulae are uncommon
      but invariably fatal if left untreated. Mortality rates of open surgery remain
      prohibitive. Thoracic endovascular aortic repair (TEVAR) was shown to be a valid
      alternative to control bleeding in emergency, allowing a reduction of
      perioperative mortality. However, it entails a significant risk of late sequelae,
      namely endograft contamination and sepsis, related to the untreated esophageal
      leak. The aim of this study is to present initial results of a combined "hybrid"
      (endovascular and open) strategy to treat AEF and ABF. MATERIALS AND METHODS:
      From 2006 to 2013, 8 patients (6 men, mean age 63 +/- 13 years) were operated at
      our institution for primary and secondary AEF (7 patients) or ABF (1 patient) by
      means of a combined approach: emergent endovascular exclusion of the aortic
      rupture, followed by staged open surgical repair of the esophageal or bronchial
      lesion with associated intercostal muscle flap interposition. Follow-up was
      available in all patients (mean 34 +/- 26 months). RESULTS: TEVAR was
      successfully performed in all cases in emergency because of active bleeding or
      hemodynamic instability. Stabilization of hemodynamic parameters was obtained in
      all patients. Open surgical stage was performed either directly after TEVAR (n =
      1) or after a mean delay of 6.9 +/- 3.5 days (n = 7). No perioperative sepsis,
      bleeding, or death was observed. At follow-up, 7 patients were alive (87.5%). One
      patient died 1 year after the procedure because of sudden cardiocirculatory
      arrest of unknown origin. Another patient experienced 2 hospitalizations, at 3
      and 8 months after the procedure, for recurrent fever requiring prolonged
      intravenous antibiotic therapy. No conversion or aortic bleeding was recorded
      during follow-up. CONCLUSIONS: Immediate TEVAR followed by staged open repair of
      the esophageal or bronchial defect with intercostal muscle flap interposition
      appears to be a feasible treatment of AEF and ABF. Despite the fact that initial
      results are encouraging, further data on wider cohorts with longer follow-up are
      necessary to confirm the efficacy and durability of this strategy.

PMID- 24930980
TI  - Technical and financial feasibility of an inferior vena cava filter retrieval
      program at a level one trauma center.
AB  - BACKGROUND: Considering new guidelines for retrievable inferior vena cava filters
      (IVCFs), we examine our initial experience after establishing a comprehensive
      filter removal program in our level 1 trauma center. We evaluated the technical
      and financial feasibility of this program and barriers to IVCF retrieval,
      including insurance status and costs, in trauma patients. METHODS: Trauma
      patients receiving IVCFs from May 2011 to 2013 were consented and prospectively
      enrolled in the study program. Retrieval rates were assessed for the years before
      study initiation. Primary outcome was IVCF retrieval. Hospital financial data for
      retrieval were examined and univariate analysis performed. Hospital cost-to
      charge and payment-to-charge ratios were assessed. RESULTS: Before study
      initiation from April 2009 to 2011, 66 IVCFs were placed in trauma patients with
      only 2 retrievals in 2 years. During the study period, 247 trauma patients had
      IVCF placement of which 111 (45%) were enrolled. The main reason for
      nonenrollment was lack of referral by the implanting team. Retrieval was
      attempted in 100 outpatients with success in 85 (85%). Patients enrolled in the
      program were more likely to have their filters removed (73% vs. 18%; odds ratio,
      12.6; 95% confidence interval, 6.6-24.3; P < 0.001). Mean time from placement to
      attempt was 6.2 +/- 4.0 months (range, 0.5-31.8). Of the total attempts, 29% were
      nonresource patients, 11% had Medicaid, and 60% had commercial insurance
      including Medicare patients. Chances of successful retrieval were higher if
      performed later during the study (P = 0.03). Successful retrieval was not related
      to insurance status (P = not significant). The mean total hospital charges
      related to retrieval were $4,493 (range, $2,510-$9,106). Successful retrieval
      contributed to lower total charges (P < 0.01). Factors contributing to higher
      total charges were retrieval attempt later in study period (P = 0.01) and
      commercial insurance status (P = 0.04). CONCLUSIONS: The rate of IVCF placement
      in trauma patients increased 4-fold over 4 years. The rate of IVCF retrieval
      increased more than 14-fold during the same period after establishment of the
      retrieval program. Elective outpatient retrieval of IVCFs in all eligible trauma
      patients is financially feasible without loss to the health care system even in
      regions with high rates of uninsured. A major barrier to successful filter
      retrieval was lack of patient referral into the program by implanting physicians.
      Hospital administration and physician outreach are important determinants of
      successful IVCF retrieval in trauma patients.

PMID- 24930981
TI  - The effects of moderate alcohol concentrations on driving and cognitive
      performance during ascending and descending blood alcohol concentrations.
AB  - OBJECTIVE: Alcohol has an adverse effect on driving performance; however, the
      effects of moderate doses on different aspects of the driving task are
      inconsistent and differ across the intoxication curve. This research aimed to
      investigate driving and cognitive performance asymmetries (acute tolerance and
      acute protracted error) accompanying the onset and recovery from moderate alcohol
      consumption. METHODS: Sixty-one participants received a placebo, medium (target
      blood alcohol concentration [BAC] 0.05 mg/ml) or high (target BAC 0.08 mg/ml)
      dose of alcohol. Participants completed a simulated drive, cognitive tests and
      subjective rating scales five times over a 3.5 h period. RESULTS: When ascending
      and descending BACs (0.05 and 0.09 mg/ml) were compared participants' self
      ratings of intoxication and willingness to drive showed acute tolerance. Acute
      protracted errors were observed for response speed, maze learning errors, time
      exceeding the speed limit and exaggerated steering responses to hazards.
      CONCLUSIONS: Participants' estimates of their level of intoxication were poorly
      related to their actual BAC levels (and hence degree of impairment), and various
      aspects of driving and cognitive performance worsened during descending BACs.
      This indicates that drivers are not good at judging their fitness to drive after
      drinking only moderate amounts of alcohol and suggests an important focus for
      public education regarding alcohol and driving.

PMID- 24930982
TI  - Infection with an apathogenic fowl adenovirus serotype-1 strain (CELO) prevents
      adenoviral gizzard erosion in broilers.
AB  - Gizzard erosion in broilers due to an infection with virulent fowl adenovirus
      serotype 1 (FAdV-1) is an emerging disease. Although experimental studies were
      performed, a possible prevention strategy was not reported so far. The present
      study was set up to determine (i) a possible influence of birds' age at time of
      inoculation on the pathogenicity of a European FAdV-1 field strain (PA7127), (ii)
      the virulence of a apathogenic FAdV-1 strain (CELO), and (iii) its capability to
      protect SPF broilers from adenoviral gizzard erosion caused by the field virus.
      Oral infection of birds with PA7127 at 1-, 10- and 21-days of life, resulted in
      reduced weight gain compared to non-infected birds, with significance for birds
      infected at day-old. Independent of the birds' age at time of inoculation,
      clinical signs appearing approximately one week after challenge coincided with
      gizzard lesions. Birds infected exclusively with CELO at the first day of life
      did not show any clinical signs or pathological changes in the gizzard,
      confirming the apathogenicity of this European FAdV-1. A similar result was
      obtained for birds orally infected at the first day of life with CELO and
      challenged three weeks later with the pathogenic PA7127 strain. Therefore,
      complete protection of adenoviral gizzard erosion in broilers by vaccination of
      day-old birds could be demonstrated for the first time, although virus excretion
      was detected post challenge. Establishment of an amplification refractory
      mutation system quantitative PCR (ARMS-qPCR) facilitated the identification of
      the FAdV-1 strain and presence of challenges virus was confirmed in one sample. 

PMID- 24930983
TI  - Proof of principle: non-invasive sampling for early detection of foot-and-mouth
      disease virus infection in wild boar using a rope-in-a-bait sampling technique.
AB  - In this study we describe the use of a rope-in-a-bait sampling method ("pSWAB":
      pathogen sampling wild animals with baits) for non-invasive saliva sampling aimed
      at the detection of foot-and-mouth disease (FMD) viral genome in wild boar. The
      pSWABs are produced in the form of a standardized product by embedding a 10 cm
      long cotton rope in a cereal-based bait matrix. To assess the general suitability
      of this novel sampling technique an animal experiment was conducted to detect FMD
      viral genome in saliva of infected wild boar. Two juvenile animals were
      inoculated in the bulb of the heel with a recent wild boar FMD virus isolate and
      kept together with three noninoculated wild boar of the same age. Over a period
      of 29 days, the animals were sampled by using five pSWABs per day in addition to
      the collection of blood and conventional saliva swabs taken every three to four
      days. Viral RNA in pSWABs was identified already 24 h after infection during the
      incubation period and until 23 dpi. Comparison of the results of pSWAB sampling
      with those of conventional saliva swabs or serum samples showed satisfactory
      sensitivity. These experimental data demonstrate the suitability of non-invasive
      sampling of wild boar by using pSWABs as a sensitive, cheap and feasible sample
      collection technique independent of hunting activities. In addition, the use of
      non-invasive sampling in an appropriate surveillance strategy is discussed.

PMID- 24930984
TI  - Lymphatic fluid for the detection of Mycobacterium avium subsp. paratuberculosis
      in cows by PCR, compared to fecal sampling and detection of antibodies in blood
      and milk.
AB  - Johne's disease (JD), caused by Mycobacterium avium subsp. paratuberculosis
      (MAP), can cause considerable economic losses in affected herds. Early diagnosis
      of JD is hampered by the chronic nature of the disease with a slow subclincal
      progression. The aim of the present study was to challenge the hypothesis that
      lymphatic fluid is of diagnostic value in the early stages of the disease.
      Lymphatic fluid from 122 animals was collected and tested for MAP by nested PCR
      for IS900 and compared to the results of testing for MAP in feces (culture),
      blood and milk (ELISA) in 110 of these samples. MAP was detected by PCR in 27.1%
      of the lymph samples. Agreement between the tests was poor: 6.9% of the lymph
      positive cows were also positive in all other tests applied, and 69.0% had
      negative results in fecal culture, blood and milk ELISA. Resampling of 25 cows
      after 8 to 12 and 16 to 20 months revealed 20.0% lymph positive animals at the
      first, 5.5% at the second and 27.8% at the third sampling, respectively. Only one
      cow showed positive lymph-PCR results at more than one sampling date. Lymph
      positive cows had a 7.2 times greater likelihood of being culled within 8 to 12
      months after sampling, compared to negative cows, mainly due to other health
      issues than JD. It can be concluded, that lymphatic fluid might be promising for
      the detection of early MAP-infection in cows, but further studies to elucidate
      the potential of this diagnostic approach are needed. 

PMID- 24930985
TI  - When 'just doing it' is not enough: assessing the fidelity of player performance
      of an injury prevention exercise program.
AB  - OBJECTIVES: To obtain benefits from sports injury prevention programs, players
      are instructed to perform the exercises as prescribed. We developed an
      observational checklist to measure the quality of exercise performance by players
      participating in FootyFirst, a coach-led, exercise-based, lower-limb injury
      prevention program in community Australian Football (AF). DESIGN: Observational.
      METHODS: The essential performance criteria for each FootyFirst exercise were
      described in terms of the technique, volume and intensity required to perform
      each exercise. An observational checklist was developed to evaluate each
      criterion through direct visual observation of players at training. The checklist
      was trialled by two independent raters who observed the same 70 players
      completing the exercises at eight clubs. Agreement between observers was assessed
      by Kappa-statistics. Exercise fidelity was defined as the proportion of observed
      players who performed all aspects of their exercises correctly. RESULTS: The
      raters agreed on 61/70 observations (87%) (Kappa=0.72, 95% CI: 0.55; 0.89). Of
      the observations with agreed ratings, 41 (67%) players were judged as performing
      the exercises as prescribed. CONCLUSIONS: The observational checklist
      demonstrated high inter-rater reliability. Many players observed did not perform
      the exercises as prescribed, raising concern as to whether they would be
      receiving anticipated program benefits. Where quality of exercise performance is
      important, evaluation and reporting of program fidelity should include direct
      observations of participants.

PMID- 24930986
TI  - Antibiotic therapy with low doses of penicillin for the secondary prevention of
      recurrent lower extremity cellulitis.

PMID- 24930987
TI  - Calcium sensing receptor in pregnancies complicated by gestational diabetes
      mellitus.
AB  - INTRODUCTION: Infants born from mothers with Gestational diabetes mellitus (GDM)
      experience several complications, including a higher rate of postnatal
      hypocalcemia. In this study, we investigated the association between calcium
      sensing receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.
      METHODS: Our study consisted of 58 pregnant women with GDM and 40 healthy women
      and their neonates. CaSR placental expression was evaluated with
      immunohistochemistry and Western Blot. Three CaSR single nucleotide
      polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate's genomic DNA.
      Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd day of
      life. RESULTS: GDM neonates had lower mean cord blood Ca levels than controls
      (2.47 +/- 0.21 mmol/l vs 2.59 +/- 0.13 mmol/l, p = 0.001) while 15.5% developed
      postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy
      placentas (p < 0.001). In the GDM group, reduced CaSR immunostaining in the
      syncytiotrophoblast (p = 0.042) and extravillous cytotrophoblasts (p = 0.002) was
      associated with lower Ca cord blood levels. Moreover, the absence of the S allele
      of the A986S polymorphism was associated with lower serum Ca levels both at birth
      (AA:2.41 +/- 0.23 mmol/l, AS + SS: 2.57 +/- 0.12 mmol/l, p = 0.002) and at 2nd
      day of life (AA:2.05 +/- 0.22 mmol/l, AS + SS: 2.20 +/- 0.18 mmol/l, p = 0.019).
      CONCLUSIONS: Our results showed that CaSR is under-expressed in GDM compared with
      healthy placentas and this alteration may be associated with the lower Ca levels
      measured in cord blood of GDM infants. Placental CaSR seems to exert a local
      effect in fetal Ca homeostasis, which is dissociated from its contribution to the
      regulation of Ca homeostasis in postnatal life.

PMID- 24930988
TI  - Maternal prepregnancy obesity is associated with higher risk of placental
      pathological lesions.
AB  - INTRODUCTION: Prepregnancy obesity is associated with increased morbidity and
      mortality for mother and offspring. The objective of our study is to estimate the
      effect of maternal prepregnancy weight on placental pathological lesions..
      METHODS: Data used for this study were from the U.S. Collaborative Perinatal
      Project, a large prospective cohort study. It consisted of 54390 women giving a
      singleton birth from 1959 to 1966. More than 84% of women had both detailed
      placental pathological examinations and anthropometric measurements. Logistic
      regression models were used to test the associations between maternal
      prepregnancy body mass index (BMI) and placental pathological lesions adjusting
      for potential confounders. Spline smoothing was applied to describe the relation
      of prepregnancy BMI and placenta weight-to-birthweight ratio. RESULTS: The
      prepregnancy obese women (BMI >= 30 kg/m(2)) showed a higher rate of maternal
      origin vascular lesions, maternal origin villous lesions, fetal neutrophilic
      infiltration, and meconium of fetal membrane compared with the normal-weight
      women (18.5 <= BMI < 24.9). The odds ratios ranged from 1.18 to 1.97 after
      adjusting for potential confounders. These higher odds were consistent in
      prepregnancy obese women without obstetric complications. Furthermore, placenta
      weight-to-birthweight ratio, the proxy for placenta insufficiency, was positively
      associated with maternal prepregnancy BMI.. CONCLUSIONS: Our study provides
      evidence that prepregnancy obesity exerts its adverse in-utero influence on
      placental pathology. These influences may have impact on maternal and fetal
      health. With obesity rising steadily, these results appear to raise serious
      public health concerns of prepregnancy obesity.

PMID- 24930989
TI  - The transcriptional activator NrpA is crucial for inducing nitrogen fixation in
      Methanosarcina mazei Go1 under nitrogen-limited conditions.
AB  - With the aim of unraveling their potential involvement in the regulation of
      nitrogen metabolism in Methanosarcina mazei strain Go1, we characterized five
      genes that are differentially transcribed in response to changing nitrogen
      availability and encoding putative transcriptional regulators. Study of the
      respective mutant strains under nitrogen-limited conditions revealed a growth
      delay for M. mazei MM0444::pac and MM1708::pac, and strongly reduced diazotrophic
      growth for MM0872::pac, whereas the absence of MM2441 or MM2525 did not affect
      growth behaviour. Transcriptome analyses further demonstrated that only MM1708 -
      encoding a CxxCG zinc finger protein - plays a regulatory role in nitrogen
      metabolism, most likely by specifically enhancing transcription of the N2
      fixation (nif) operon under nitrogen-limited conditions. In agreement with this,
      a palindromic binding motif was predicted in silico in the nifH promoter region,
      nine nucleotides upstream of the BRE box, and confirmed to bind purified maltose
      binding protein-MM1708 by electromobility shift assays. As MM1708 itself is under
      the control of the global nitrogen repressor NrpR, this adds a secondary level to
      the transcriptional regulation of the nif genes, and is most likely crucial for
      maximal nif induction under nitrogen-limited conditions. This is in accordance
      with the finding that protein expression of NifH is highly reduced in the absence
      of MM1708 under nitrogen-limited conditions. On the basis of our findings, we
      hypothesize that, in M. mazei, nitrogen fixation is controlled by a hierarchical
      network of two transcriptional regulators, the global nitrogen repressor NrpR,
      and the newly identified activator NrpA (MM1708), thereby providing tight control
      of N2 fixation.

PMID- 24930991
TI  - Is the S405F mutation in Candida albicans ERG11 gene sufficient to confer
      resistance to fluconazole?

PMID- 24930990
TI  - Anticandidal activity of silver nanoparticles synthesized using Streptomyces
      sp.VITPK1.
AB  - OBJECTIVES: The aim of the present study was to evaluate the anticandidal
      activity of biologically synthesized silver nanoparticles using the culture
      filtrate of Streptomyces sp.VITPK1. MATERIALS AND METHODS: Silver nanoparticles
      were synthesized using the culture filtrate of Streptomyces species isolated from
      brine spring located at Thoubal District, Manipur, India. The isolate was
      identified by molecular taxonomic characterization and designated as Streptomyces
      sp.VITPK1. The synthesized silver nanoparticles (AgNPs) were characterized by UV
      visible spectra, X-ray diffraction (XRD) patterns, Energy Dispersive Analysis of
      X-rays (EDAX) and Fourier Transform Infrared (FTIR) analysis. The antifungal
      activity of the synthesized silver nanoparticles was evaluated against selected
      Candida species. RESULTS: The synthesized AgNPs showed a surface plasmon
      resonance peak at 425 nm. XRD patterns showed the crystalline peaks at 38.15
      degrees  (111), 44.35 degrees  (200), 64.52 degrees  (220) and 77.49 degrees 
      (311) matching with the diffraction facets of silver. The size of the AgNPs was
      in the range of 20-45 nm. The EDAX analysis revealed the presence of silver as
      the major metal in the sample. The synthesized AgNPs showed anticandidal activity
      against Candida albicans, Candida tropicalis and Candida krusei with a maximum
      zone of inhibition of 20mm against C. albicans. CONCLUSIONS: The results of this
      study suggest that the green synthesis of silver nanoparticles using Streptomyces
      sp.VITPK1 have the ability to act against pathogenic Candida strains.

PMID- 24930992
TI  - A national survey of spinal cord stimulation trial-to-permanent conversion rates.
AB  - OBJECTIVES: Conversion rates from trial leads to permanent spinal cord
      stimulation (SCS) systems have recently come under scrutiny. Our goal was to
      examine the rate of conversion from trial lead to permanent system placement as
      well as identify factors associated with successful SCS conversion. MATERIALS AND
      METHODS: We designed a large retrospective analysis using the Thomson Reuters
      MarketScan database. We included all patients who underwent a percutaneous trial
      of neurostimulatory electrodes from the years 2000 to 2009 who were aged 18 and
      older. Patients were then tracked to see if they went on to receive a permanent
      SCS system. Patients were also analyzed in univariate and multivariate models to
      identify factors associated with successful conversion. RESULTS: A total of
      21,672 unique instances of percutaneous trials were identified. Overall, 41.4% of
      those receiving trials went on to have a permanent SCS system installed within
      the subsequent three months. Factors associated with increased likelihood of
      successful conversion included having commercial insurance (43% vs. 37%, p <
      0.0001), younger age (43% for those aged 35-44 vs. 39% for those aged 65 and
      older, p < 0.0001), and never having had a previous percutaneous trial attempt
      (44% for first-time trials vs. 27% for those on their second trial vs. 14% for
      those on their third or later trial, p < 0.0001). In multivariate analysis, we
      found significant variation in conversion rate by geographic area (patients in
      the North Central region vs. Northeast region: odds ratio 1.48, 95% confidence
      interval [1.31, 1.66]; p < 0.0001). CONCLUSIONS: In this study of a national
      cohort of patients, we identified specific factors associated with higher
      conversion rates, along with significant geographical variation. In general,
      there is a need for better patient selection by physicians who practice
      neuromodulation.

PMID- 24930993
TI  - Testosterone therapy, thrombosis, thrombophilia, cardiovascular events.
AB  - There are similar time intervals between starting testosterone therapy (TT) and
      development of thrombotic (~4.5 months) or cardiovascular (CVD) events (~3
      months) which may, speculatively, reflect a shared pathophysiology. We have
      described thrombotic events 5 months (median) after starting TT in 38 men and 4
      women, including 27 with deep venous thrombosis-pulmonary embolism, 12 with
      osteonecrosis, 1 with central retinal vein thrombosis, 1 with amaurosis fugax,
      and 1 with spinal cord infarction. In 8 men whose TT was continued, second
      thrombotic events occurred despite adequate anticoagulation with Coumadin in 8
      men, 3 of whom had a third thrombotic event. Of these 42 cases, 40 had measures
      of thrombophilia-hypofibrinolysis, and 39 were found to have previously
      undiagnosed thrombophilia-hypofibrinolysis. Before beginning TT, especially in
      men with previous history of thrombotic events, we suggest that, at a minimum,
      measurements be made for the Factor V Leiden and Prothrombin mutations, Factors
      VIII and XI, and homocysteine, to identify men who should not receive TT. We need
      prospective data focused on whether there should be pre-TT screening based on
      history of previous venous thromboembolism or for all subjects for major gene
      thrombophilias. To better resolve questions about TT and all cause and
      cardiovascular morbidity and mortality and thrombosis, a long term, prospective,
      randomized, blinded study following the example of the Women's Health Initiative
      is needed. While we wait for prospective placebo-controlled TT outcome data, TT
      should be restricted to men with well-defined androgen deficiency syndromes.

PMID- 24930994
TI  - JAZF1 regulates visfatin expression in adipocytes via PPARalpha and
      PPARbeta/delta signaling.
AB  - OBJECTIVE: Current whole genome-wide association study has identified the
      association of JAZF1 with type 2 diabetes; its close relation with glucose and
      lipid metabolism has also been revealed. However, to date, JAZF1 remains a
      relatively new gene with unknown function. MATERIALS/METHODS: We constructed
      JAZF1 overexpression vector and synthesized JAZF1 siRNA, then transfected them
      into 3T3-L1 adipocytes, investigated the relationship between the regulations of
      JAZF1, visfatin, and other adipokines, researched the specific function of JAZF1
      in glucose and lipid metabolism. RESULTS: This study found that the expression of
      JAZF1 was gradually but significantly upregulated during the induced
      differentiation of 3T3-L1 preadipocytes, and that the trend of its expression was
      consistent with that of visfatin. Further studies indicated that JAZF1 promoted
      the expressions of visfatin, PPARalpha, and PPARbeta/delta in adipocytes but
      simultaneously inhibited the expressions of TAK1 and PPARgamma. Luciferase
      reporter assay revealed that JAZF1 activated the transcription of visfatin, but
      ChIP assay results indicated that JAZF1 did not directly bind to visfatin PPRE.
      Our results also showed that the JAZF1 overexpression-increased visfatin
      expression was abolished by the addition of PPARalpha antagonist GW 6471 and
      PPARbeta/delta antagonist GSK 3787 respectively. And these results were further
      confirmed by the experiment with PPARalpha and PPARbeta/delta siRNAs. Meanwhile,
      we also found that JAZF1 inhibited the lipid accumulation during the
      differentiation of 3T3-L1 into mature adipocyte. CONCLUSIONS: Our results
      indicate that JAZF1 might firstly upregulated the expression of PPARalpha and
      PPARbeta/delta, which in turn activated the transcription of visfatin. JAZF1
      plays an important role in lipid metabolism and may thus provide a potential tool
      for the treatment of obesity and lipid metabolism disorders among other diseases.

PMID- 24930995
TI  - Effect of propiverine hydrochloride on stress urinary incontinence.
AB  - OBJECTIVES: To investigate whether the anticholinergic agent, propiverine
      hydrochloride, is clinically effective for stress urinary incontinence. METHODS:
      The participants were adult female patients with the chief complaint of stress
      incontinence. Propiverine (20 mg once daily) was given for 8 weeks. If the
      response was inadequate after 4 weeks of treatment, the dose was increased to 40
      mg/day. Before and after 4 and 8 weeks of treatment, lower urinary tract symptoms
      were assessed. The urethral pressure and blood catecholamine levels were also
      measured. RESULTS: A total of 37 patients (mean age 69 +/- 11 years) were
      enrolled, including 15 patients with stress incontinence and 22 with mixed
      incontinence. The number of episodes of stress incontinence decreased
      significantly from 2.6 +/- 2.3 times per day to 1.3 +/- 2.2 times per day after 4
      weeks, and 0.4 +/- 0.6 times per day after 8 weeks. The daytime and night-time
      frequency of urination, and quality of life score showed significant improvement.
      The maximum urethral closing pressure and the functional urethral length
      increased significantly after treatment, but blood catecholamine levels, blood
      pressure and pulse rate at 8 weeks were not significantly different from those at
      baseline. CONCLUSIONS: Propiverine could be an effective drug for stress urinary
      incontinence by increasing urethral closing pressure without increasing blood
      catecholamine levels.

PMID- 24930997
TI  - Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes
      Project data.
AB  - BACKGROUND: Genome-wide association studies (GWAS) repeatedly identified 1q23
      (FCER1A), 5q31 (RAD50-IL13 and IL4), and 12q13 (STAT6) as major susceptibility
      loci influencing the regulation of total serum IgE levels. As GWAS may be
      insufficient to capture causal variants, we performed fine-mapping and re
      genotyping of the three loci using 1000 Genomes Project datasets. METHODS:
      Linkage disequilibrium tagging polymorphisms and polymorphisms of putative
      functional relevance were genotyped by chip technology (24 polymorphisms) or
      MALDI-TOF-MS (40 polymorphisms) in at least 1303 German children (651
      asthmatics). The effect of polymorphisms on total serum IgE, IgE percentiles, and
      atopic diseases was assessed, and a risk score model was applied for gene-by-gene
      interaction analyses. Functional effects of putative causal variants from these
      three loci were studied in silico. RESULTS: Associations from GWAS were confirmed
      and extended. For 1q23 and 5q31, the majority of associations were found with
      mild to moderately elevated IgE levels, while in the 12q13 locus, single
      nucleotide polymorphisms (SNPs) were associated with strongly elevated IgE
      levels. Gene-by-gene interaction analyses suggested that the presence of
      mutations in all three loci increases the risk for elevated IgE up to fourfold.
      CONCLUSION: This fine-mapping study confirmed previous associations and
      identified novel associations of SNPs in 1q23, 5q31, and 12q13 with different
      levels of serum IgE and their concomitant contribution to IgE regulation.

PMID- 24930998
TI  - Melt crystallization/dewetting of ultrathin PEO films via carbon dioxide
      annealing: the effects of polymer adsorbed layers.
AB  - The effects of CO2 annealing on the melting and subsequent melt crystallization
      processes of spin-cast poly(ethylene oxide) (PEO) ultrathin films (20-100 nm in
      thickness) prepared on Si substrates were investigated. By using in situ neutron
      reflectivity, we found that all the PEO thin films show melting at a pressure as
      low as P = 2.9 MPa and at T = 48  degrees C which is below the bulk melting
      temperature (Tm). The films were then subjected to quick depressurization to
      atmospheric pressure, resulting in the non-equilibrium swollen state, and the
      melt crystallization (and/or dewetting) process was carried out in air via
      subsequent annealing at given temperatures below Tm. Detailed structural
      characterization using grazing incidence X-ray diffraction, atomic force
      microscopy, and polarized optical microscopy revealed two unique aspects of the
      CO2-treated PEO films: (i) a flat-on lamellar orientation, where the molecular
      chains stand normal to the film surface, is formed within the entire film
      regardless of the original film thickness and the annealing temperature; and (ii)
      the dewetting kinetics for the 20 nm thick film is much slower than that for the
      thicker films. The key to these phenomena is the formation of irreversibly
      adsorbed layers on the substrates during the CO2 annealing: the limited
      plasticization effect of CO2 at the polymer-substrate interface promotes polymer
      adsorption rather than melting. Here we explain the mechanisms of the melt
      crystallization and dewetting processes where the adsorbed layers play vital
      roles. 

PMID- 24930996
TI  - Gait changes with balance-based torso-weighting in people with multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: People with multiple sclerosis (PwMS) commonly have
      mobility impairments that may lead to falls and limitations in activities.
      Physiotherapy interventions that might improve mobility typically take several
      weeks. Balance-based torso-weighting (BBTW), a system of strategically placing
      light weights to improve response to balance perturbations, has resulted in
      immediate small improvements in clinical measures in PwMS, but changes in
      spatiotemporal gait parameters are unknown. The purpose was to investigate the
      effects of BBTW on gait parameters in PwMS and healthy controls. METHODS DESIGN:
      This study is a non-randomized controlled experiment. PARTICIPANTS: This study
      included 20 PwMS and 20 matched healthy controls PROCEDURES: People with multiple
      sclerosis walked on an instrumented mat at their fastest speed for three trials
      each in two conditions: without BBTW then with BBTW. Healthy controls walked in
      both conditions at two speeds: their fastest speed and at velocities equivalent
      to their matched PwMS. RESULTS: Averaged gait trials showed that, with BBTW, PwMS
      had significantly increased velocity (p = 0.002), cadence (p = 0.007) and time
      spent in single-limb support (p = 0.014), with decreased time in double-limb
      support (p = 0.004). Healthy controls increased velocity (p = 0.012) and cadence
      (p = 0.015) and decreased support base (p = 0.014) in fast trials with BBTW; at
      matched velocities, step length (p = 0.028) and support base (p = 0.006) were
      significantly different from PwMS. All gait variables in healthy controls at fast
      speeds were significantly different from PwMS walking at their fastest speeds.
      DISCUSSION: All participants showed increases in gait velocity and cadence during
      fast walk with BBTW. Improvements in time spent in single-limb and double-limb
      support by PwMS with BBTW may reflect greater stability in gait. Future research
      might ascertain if these immediate improvements could enhance effectiveness of
      longer-term physiotherapy on functional mobility in PwMS.

PMID- 24930999
TI  - Evaluating pharmacist prescribing for minor ailments.
AB  - OBJECTIVES: Saskatchewan is the second Canadian province to allow pharmacists to
      prescribe medications for minor ailments and the only province that remunerates
      for this activity. The aim of this project was to determine whether patients
      prescribed such treatment by a pharmacist symptomatically improve within a set
      time frame. METHODS: Pharmacists were asked to hand a study-invitation card to
      anyone for whom they prescribed a medication for a minor ailment during the 1
      year study period. Consenting participants contacted the study researchers
      directly and were subsequently instructed to complete an online questionnaire at
      the appropriate follow-up time. KEY FINDINGS: Ninety pharmacies in Saskatchewan
      participated, accruing 125 participants. Cold sores were the most common minor
      ailment (34.4%), followed by insect bites (20%) and seasonal allergies (19.2%).
      Trust in pharmacists and convenience were the most common reasons for choosing a
      pharmacist over a physician, and 27.2% would have chosen a physician or emergency
      department if the minor ailment service were not available. The condition
      significantly/completely improved in 80.8%; only 4% experienced bothersome side
      effects. Satisfaction with the pharmacist and service was strong; only 5.6% felt
      a physician would have been more thorough. CONCLUSIONS: Participants were very
      satisfied with their symptomatic improvement and with the service in general,
      albeit for a small number of conditions. Participants reported getting better,
      and side effects were not a concern. These results are encouraging for
      pharmacists; however, a comparison of physician care with pharmacist care and
      unsupported self-care is required to truly know the benefit of pharmacist
      prescribing.

PMID- 24931000
TI  - In vitro evaluation of combination of polyenes with EDTA against Aspergillus spp.
      by different methods (FICI and CI Model).
AB  - AIMS: We investigated in vitro activity of polyene drugs (amphotericin B, Amp B;
      and nystatin, NYS;) in combination with ethylene diamine tetra acetic acid (EDTA)
      against 8 pathogenic isolates of Aspergillus spp. METHODS AND RESULTS: The
      intensity of the drug interactions was assessed using Fractional Inhibitory
      Concentration Index (FICI) model and Combination Index (CI) model. The
      interactions were further confirmed by time-kill curve study. The best
      combination ratio was subjected for toxicity analysis by MTT and haemolytic
      assay. A significant synergy was found between each of two polyenes with EDTA
      against Aspergillus fumigatus and Aspergillus flavus at one ratio four. The FICI
      ranged from 0.29 to 0.38 against A. fumigatus and A. flavus. The FICI value
      ranged from 0.78 to 1.26 showed no interaction against Aspergillus niger. The CI
      value (0.21-0.30) and time-kill curve analysis also confirmed synergistic
      interaction. Antagonism was not detected. There was reduction in toxicity of Amp
      B and NYS when used with EDTA. CONCLUSIONS: Subsequently, the chelating agent
      (EDTA) can be used in combination with Amp B and NYS with increased antifungal
      potential and reduced toxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: To
      emphasize new development in antifungal drug discovery, combination therapy can
      be used as a tool box to expand drug development.

PMID- 24931001
TI  - Cardiac cycle time effects on mask inhibition.
AB  - Research on the interaction of the cardiovascular and the central nervous system
      has demonstrated inhibitory effects associated with baroreceptor stimulation. One
      way of examining baroreceptor influence on behavior and central nervous processes
      is by making use of naturally occurring variations in baroreceptor stimulation in
      the course of the cardiac cycle. In terms of perceptual and sensorimotor
      processes, until today, research has focused primarily on cardiac cycle time
      effects on the perception of and reaction to simple stimuli. The present study is
      the first to investigate modulatory effects of variations in baroreceptor
      activity in the context of a more complex stimulus configuration using a visual
      masking task in which a target has to be selected against an interfering mask.
      The results suggest that baroreceptor stimulation enhances inhibitory processes
      needed to solve perceptual interference. 

PMID- 24931002
TI  - Clinical perspective of cell-free DNA testing for fetal aneuploidies.
AB  - Cell-free DNA testing in maternal blood provides the most effective method of
      screening for trisomy 21, with a reported detection rate of 99% and a false
      positive rate of less than 0.1%. After many years of research, this method is now
      commercially available and is carried out in an increasing number of patients,
      and there is an expanding number of conditions that can be screened for. However,
      the application of these methods in clinical practice requires a careful
      analysis. Current first-trimester screening strategies are based on a complex
      combination of tests, aiming at detecting fetal defects and predicting the risk
      of main pregnancy complications. It is therefore necessary to define the optimal
      way of combining cell-free DNA testing with current first-trimester screening
      methods. In this concise review we describe the basis of cell-free DNA testing
      and discuss the potential approaches for its implementation in combination with
      current tests in the first trimester.

PMID- 24931003
TI  - Maca reduces blood pressure and depression, in a pilot study in postmenopausal
      women.
AB  - OBJECTIVE: Lepidium meyenii (Maca) has been used for centuries for its fertility
      enhancing and aphrodisiac properties. In an Australian study, Maca improved
      anxiety and depressive scores. The effects of Maca on hormones, lipids, glucose,
      serum cytokines, blood pressure, menopausal symptoms and general well-being in
      Chinese postmenopausal women were evaluated. METHODS: A randomized, double-blind,
      placebo-controlled, cross-over study was conducted in 29 postmenopausal Hong Kong
      Chinese women. They received 3.3 g/day of Maca or placebo for 6 weeks each, in
      either order, over 12 weeks. At baseline, week 6 and week 12, estradiol, follicle
      stimulating hormone (FSH), sex hormone binding globulin (SHBG), thyroid
      stimulating hormone (TSH), full lipid profiles, glucose and serum cytokines were
      measured. The Greene Climacteric, SF-36 Version 2, Women's Health Questionnaire
      and Utian Quality of Life Scales were used to assess the severity of menopausal
      symptoms and health-related quality of life. RESULTS: There were no differences
      in estradiol, FSH, TSH, SHBG, glucose, lipid profiles and serum cytokines amongst
      those who received Maca as compared to the placebo group; however, significant
      decreases in diastolic blood pressure and depression were apparent after Maca
      treatment. CONCLUSIONS: Maca did not exert hormonal or immune biological action
      in the small cohort of patients studied; however, it appeared to reduce symptoms
      of depression and improve diastolic blood pressure in Chinese postmenopausal
      women. Although results are comparable to previous similar published studies in
      postmenopausal women, there might be a cultural difference among the Chinese
      postmenopausal women in terms of symptom reporting.

PMID- 24931004
TI  - Odd-skipped related 1 is a novel tumour suppressor gene and a potential
      prognostic biomarker in gastric cancer.
AB  - We report that the odd-skipped related 1 (OSR1) gene encoding a zinc-finger
      transcription factor was preferentially methylated in gastric cancer by genome
      wide methylation screening. OSR1 expression was frequently silenced or down
      regulated in gastric cancer cell lines. OSR1 expression was also significantly
      down-regulated at both mRNA and protein levels in primary gastric cancer tissues
      compared with adjacent normal tissues. The silencing or down-regulation of OSR1
      was closely associated with promoter hypermethylation. Overexpression of OSR1
      significantly inhibited cell growth, arrested the cell cycle, and induced
      apoptosis in the gastric cancer cell lines AGS, MKN28, and MGC803. Conversely,
      knockdown of OSR1 by OSR1-short hairpin RNA significantly enhanced cell growth,
      promoted the cell cycle, and inhibited apoptosis in the normal gastric epithelial
      cell line GES1. The dual-luciferase reporter assay revealed that OSR1 activated
      p53 transcription and repressed the T-cell factor (TCF)/lymphoid enhancer factor
      (LEF). Complementary DNA expression array and western blotting showed that OSR1
      increased the expression of nuclear p53, p21, Fas, and death receptor-5, and
      suppressed the expression of cyclin D1 and cyclin-dependent kinase 4 in the p53
      signalling pathway. In addition, OSR1 suppressed the expression of cytoplasmic
      beta-catenin, TCF-1, and LEF1 in the Wnt/beta-catenin signalling pathway. OSR1
      methylation was detected in 51.8% of primary gastric cancer patients (85 of 164)
      by bisulphite genomic sequencing. Multivariate Cox regression analysis showed
      that OSR1 methylation was an independent predictor of poor survival. Kaplan-Meier
      survival curves revealed that OSR1 methylation was associated with shortened
      survival in TNM stage I-III patients. In conclusion, OSR1 acts as a functional
      tumour suppressor through the transcriptional activation of p53 and repression of
      TCF/LEF in gastric cancer. Detection of OSR1 methylation may serve as a potential
      biomarker of the early stage of gastric cancer.

PMID- 24931006
TI  - Caspase-8-mediated PAR-4 cleavage is required for TNFalpha-induced apoptosis.
AB  - The tumor suppressor protein prostate apoptosis response-4 (PAR-4) is silenced in
      a subset of human cancers and its down-regulation serves as a mechanism for
      cancer cell survival following chemotherapy. PAR-4 re-expression selectively
      causes apoptosis in cancer cells but how its pro-apoptotic functions are
      controlled and executed precisely is currently unknown. We demonstrate here that
      UV-induced apoptosis results in a rapid caspase-dependent PAR-4 cleavage at
      EEPD131G, a sequence that was preferentially recognized by caspase-8. To
      investigate the effect on cell growth for this cleavage event we established
      stable cell lines that express wild-type-PAR-4 or the caspase cleavage resistant
      mutant PAR-4 D131G under the control of a doxycycline-inducible promoter.
      Induction of the wild-type protein but not the mutant interfered with cell
      proliferation, predominantly through induction of apoptosis. We further
      demonstrate that TNFalpha-induced apoptosis leads to caspase-8-dependent PAR-4
      cleavage followed by nuclear accumulation of the C-terminal PAR-4 (132-340)
      fragment, which then induces apoptosis. Taken together, our results indicate that
      the mechanism by which PAR-4 orchestrates the apoptotic process requires cleavage
      by caspase-8.

PMID- 24931007
TI  - Dysmorphogenic effects of first trimester-equivalent ethanol exposure in mice: a
      magnetic resonance microscopy-based study.
AB  - BACKGROUND: The first trimester of human development and the equivalent
      developmental period in animal models is a time when teratogenic ethanol (EtOH)
      exposure induces the major structural birth defects that fall within fetal
      alcohol spectrum disorder (FASD). Previous FASD research employing an acute high
      dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive
      periods for a number of these defects. Extending this work, this investigation
      utilized high resolution magnetic resonance microscopy (MRM)-based analyses to
      examine the dysmorphology resulting from maternal dietary EtOH intake occurring
      during selected first trimester-equivalent time periods. METHODS: Female C57Bl/6J
      mice were acclimated to a liquid 4.8% EtOH (v/v)-containing diet, then bred while
      on standard chow. Dams were again provided the EtOH-containing liquid diet for a
      period that extended either from the beginning of gestational day (GD) 7 to the
      end of GD 11 or from the beginning of GD 12 to the end of GD 16. On GD 17, a
      subset of fetuses was selected for MRM-based analyses. Group comparisons were
      made for litter characteristics and gross dysmorphology, as well as whole and
      regional brain volumes. RESULTS: EtOH-induced stage of exposure-dependent
      structural brain abnormalities were observed. The GD 7 to 11 EtOH-exposed group
      presented with a significant decrease in cerebellar volume and an increase in
      septal volume, while GD 12 to 16 EtOH treatment resulted in a reduction in right
      hippocampal volume accompanied by enlarged pituitaries. Additionally, the GD 12
      to 16 EtOH exposure caused a high incidence of edema/fetal hydrops. CONCLUSIONS:
      These results illustrate the teratogenic impact of maternal dietary EtOH intake
      occurring at time periods approximately equivalent to weeks 3 through 6 (GD 7 to
      11 in mice) and weeks 7 through 12 (GD 12 to 16 in mice) of human gestation,
      further documenting EtOH's stage of exposure-dependent neuroteratogenic end
      points and highlighting the vulnerability of selected brain regions during the
      first trimester. Additionally they suggest that clinical attention should be paid
      to fetal hydrops as a likely component of FASD.

PMID- 24931008
TI  - Neurophysiological abnormalities in the sensorimotor cortices during the motor
      planning and movement execution stages of children with cerebral palsy.
AB  - AIM: This investigation used magnetoencephalography (MEG) to examine the neural
      oscillatory responses of the sensorimotor cortices during the motor planning and
      movement execution stages of children with typical development and children with
      cerebral palsy (CP). METHOD: The study involved 13 children with CP (nine males,
      four females; mean [SD] age 14y 3mo [9mo], range 10-18y; height 1.61m [0.08m];
      weight 52.65kg [13kg]), and 13 age- and sex-matched typically developing children
      (height 1.64m [0.06m]; weight 56.88kg [10kg]). The experiment required the
      children to extend their knee joint as whole-head MEG recordings were acquired.
      Beamformer imaging methods were employed to quantify the source activity of the
      beta-frequency (14-28Hz) event-related desynchronization (ERD) that occurs during
      the motor planning period, and the gamma-frequency (~50Hz) event-related
      synchronization (ERS) that occurs at the motor execution stage. RESULTS: The
      children with CP had a stronger mean beta ERD during the motor planning phase and
      reduced mean gamma ERS at the onset of movement. INTERPRETATION: The
      uncharacteristic beta ERD in the children with CP suggests that they may have
      greater difficulty planning knee joint movements. We suggest that these aberrant
      beta ERD oscillations may have a cascading effect on the gamma ERS, which
      ultimately affects the execution of the motor command.

PMID- 24931009
TI  - Long-term outcome of pediatric renal transplantation: a single center study in
      Japan.
AB  - Little is known about the risk factors for long-term poor outcome in pediatric
      renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living
      donations) were performed in 104 children (56 males, mean age, 12.5 yr) at the
      Social Insurance Chukyo Hospital, and followed-up for a mean period of 13.6 yr.
      The patient survival at 1, 5, 10, 15, 20 (living- and deceased-donor
      transplants), and 30 yr (living-donor transplants only) was 98.1%, 92.8%, 87.8%,
      84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30 yr was
      92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss
      was CAI, AR, death with functioning, recurrent primary disease, ATN, and
      malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras
      affected patient survival. AR and CAI were the risk factors for graft loss. The
      evolved immunosuppression protocols improved the outcome by reducing AR episodes
      and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI
      was correlated with AR episodes, CMV infection, and post-transplant hypertension.
      Strategies for preventing the risk factors for malignancy/cardiovascular events
      and CAI, including hypertension/infection, are crucial for better outcomes. 

PMID- 24931011
TI  - [Unmet needs in the treatment of allergic rhinitis in China].

PMID- 24931012
TI  - [Diagnosis and management of allergic rhinitis in the geriatric population].

PMID- 24931010
TI  - Intracardiac mass as initial cardiac manifestation of Behcet's disease: think
      before you cut.
AB  - Behcet's disease (BD) is a chronic multisystemic inflammatory disorder. Cardiac
      abnormalities including intracardiac thrombi have been described in up to 16% of
      cases. The clinical presentation of cardiac complications in BD may include
      fever, dyspnea, chest pain, hemoptysis, and edema. We present 2 cases of patients
      who underwent surgical excision of intracardiac masses thought to be intracardiac
      malignancies. Further pathological and clinical evaluation established
      intracardiac inflammatory masses due to BD as the final diagnosis. As
      intracardiac masses may be the presenting manifestation of BD, it is crucial for
      echocardiographers to consider BD in the differential diagnosis. A careful
      history and physical exam looking for signs and symptoms of BD is critical before
      considering surgical excision of unexplained intracardiac masses. If the final
      diagnosis is BD anti-inflammatory therapy should be considered the basis of
      treatment. 

PMID- 24931013
TI  - [Onset feature and efficacy of early interventional treatment of Artemisia
      pollinosis].
AB  - OBJECTIVE: To analyze the clinical feature and treatment methods of Artemisia
      pollinosis. METHODS: Skin prick test results of 14 426 cases from Beijing Tongren
      hospital and pollen concentration of Beijing observatory from 2007 to 2011 were
      analyzed to identify the clinical feature of Artemisia pollinosis patients and
      its correlation with the pollen concentration. Patients were given leukotriene
      receptor antagonists (Montelukast) for 2 weeks, followed by 4 weeks of mometasone
      furoate nasal spray (EIT group: n = 21), or only 4 weeks of mometasone furoate
      nasal spray (POT group: n = 16). The nasal symptom score was compared between 2
      groups.SPSS 16.0 software was used to analyze the data. RESULTS: Artemisia
      pollinosis accounted for 30.8% (4 442/14 426) of all SPT positive allergic
      rhinitis patients, and most Artemisia SPT positive results were strong positive(3
      793/4 442, 85.4%); onset age peak of Artemisia pollinosis patients was at the age
      of 19 to 30, onset time concentrated in August to September, was consistent with
      the peak period of Artemisia pollen concentration; EIT treatment using
      leukotriene receptor antagonists two weeks before pollen season significantly
      improved sneeze, sniveling and rhinocnesmus symptoms (t value was 3.28, 3.92,
      3.09, respectively, all P < 0.01) compared with post-onset treatment (POT). But
      nasal obstruction and cough symptoms had no significant difference between two
      groups (t value was 0.85, 1.52, respectively, all P > 0.05). CONCLUSION:
      Artemisia pollen is the main pollen allergen in Beijing, EIT treatment was
      effective to pollinosis.

PMID- 24931014
TI  - [The high risk factors of allergen sensitization among 518 children with allergic
      rhinitis symptoms].
AB  - OBJECTIVE: To study the high risk factors of allergen sensitization among 1-16
      years old children with allergic rhinitis (AR) symptoms. METHODS: Medical history
      was collected from 518 children with AR symptoms aged 1 to 16 years old between
      April 2011 and November 2012, including five aspects:basic information, disease
      characteristics, associated with other allergic diseases, growth and development
      history and genetic history and so on. The allergens were determined by UniCAP
      100 system. The high risk factors of allergen sensitization (sIgE >= grade III)
      among 1-16 years old children with AR symptoms were analyzed. The data processing
      and statistical analysis were conducted by SPSS 17.0 software. RESULTS: Three
      hundred and thirty of 518 patients (63.7%) could be diagnosed as AR. The primary
      allergen was mixed fungal (52.4%). The highest percentage of allergen sIgE >=
      grade III accounted for the corresponding allergen positive cases was 71.1%
      (mixed fungal). Single factor analysis of clinical characteristics in the groups
      of AR and non AR showed that the history of months(chi(2) = -3.591), concomitant
      allergic conjunctivitis (chi(2) = 12.325) and cats or dogs at home (chi(2) =
      5.615) were statistically significant between the two groups (all P < 0.05).In
      children with AR, single factor analysis of clinical characteristics in the
      groups of whether positive allergen level >= grade III showed that the
      concomitant asthma(chi(2) = 4.097), breastfeeding(chi(2) = 4.186), the housing
      situation (chi(2) = 4.360) and the bedroom toward (chi(2) = 4.656) were
      statistically significant between the two groups (all P < 0.05). In children with
      AR, single factor analysis of clinical characteristics in different age groups
      showed that the history of months(chi(2) = 64.999), concomitant eczema (chi(2) =
      24.056), concomitant insect bite dermatitis (chi(2) = 9.148), cats or dogs at
      home (chi(2) = 8.529) and mother suffered from AR (chi(2) = 9.565) were
      statistically significant in different age groups (all P < 0.05). CONCLUSION: The
      study revealed that the longer of history, concomitant allergic conjunctivitis
      and cats or dogs at home are risk factors for AR;In children with AR, not
      breastfeeding and the bedroom toward back are risk factors for inhalation
      allergen sIgE >= gradeIII.

PMID- 24931005
TI  - GSK-3 as potential target for therapeutic intervention in cancer.
AB  - The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially
      identified and studied in the regulation of glycogen synthesis. GSK-3 functions
      in a wide range of cellular processes. Aberrant activity of GSK-3 has been
      implicated in many human pathologies including: bipolar depression, Alzheimer's
      disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus
      (NIDDM) and others. In some cases, suppression of GSK-3 activity by
      phosphorylation by Akt and other kinases has been associated with cancer
      progression. In these cases, GSK-3 has tumor suppressor functions. In other
      cases, GSK-3 has been associated with tumor progression by stabilizing components
      of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties.
      While many inhibitors to GSK-3 have been developed, their use remains
      controversial because of the ambiguous role of GSK-3 in cancer development. In
      this review, we will focus on the diverse roles that GSK-3 plays in various human
      cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated
      in the generation of cancer stem cells in various cell types. We will also
      discuss how this pivotal kinase interacts with multiple signaling pathways such
      as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and
      others. 

PMID- 24931015
TI  - [Investigation on the role of TIM4 in the pathogenesis of allergic rhinitis in
      mice].
AB  - OBJECTIVE: To investigate the role of TIM4 (T cell immunoglobulin and mucin
      domain molecule 4) in the pathogenesis of allergic rhinitis (AR) in mice, and to
      identify a novel therapeutic target for the treatment of AR. METHODS: Twenty-one
      male BALB/C mice of clean grade were divided into three groups randomly (n = 7
      per group) including control, AR and anti-TIM4 antibody treatment groups. In
      order to induce upper airway allergic inflammation, the mice from AR and anti
      TIM4 antibody treatment groups were sensitized by intraperitoneal injection
      followed by intranasal challenge with ovalbumin. Before the ovalbumin challenge,
      a group of mice was treated with anti-TIM4 antibody. To assess the AR model,
      behavioral observation with immunological assessments and HE staining of nasal
      tissues were performed. The TIM4 expression in nasal tissues in different groups
      of mice were assessed by immunofluorescence and RT-PCR.SPSS18.0 software was used
      to analyze the data. RESULTS: The AR model in mice was successfully established
      as shown by behavioral observation and immunological evaluation. RT-PCR assays
      showed the relative expression of TIM4 mRNA in nasal mucosa of AR, control and
      anti-TIM4 antibody treatment mice was 16.29 +/- 3.80, 0.51 +/- 0.60, 1.64 +/-
      0.98, respectively. There was statistically significant differences mong three
      group (F = 46.56, P < 0.05). The expression of TIM4 in AR group was significantly
      higher than those in control group (t = 8.650, P < 0.05) and anti-TIM4 group (t =
      8.027, P < 0.05). The expression of TIM4 was significantly reduced in the anti
      TIM4 antibody group, as well as control group (t = -0.623, P > 0.05). More
      expression of TIM4 was detected in local nasal tissues of AR mice, mainly located
      below the pseudostratified ciliated columnar epithelium. CONCLUSIONS: TIM4 plays
      a crucial role in the pathogenesis of AR. Effective inhibition of TIM4 expression
      can partially reverse the pathological changes of AR.

PMID- 24931016
TI  - [Role of immune deviation by toll-liked receptor's doping LPS in pathogenesis of
      allergic rhinitis].
AB  - OBJECTIVES: To investigate the role of TLR-NF-kappaB signaling pathway in
      pathogenesis of allergic rhinitis (AR) and the mechanism of TLR to modulate
      innate immunity and adaptive immunity. METHODS: One hundred rats were divided
      into 5 groups by simple randomization, normal group(group A), modle group(group
      B), AR+LPS20 group(group C), AR+LPS10 group(group D), AR+LPS5 group(group E).
      Model of AR in B group was established by intraperitoneal injection and nasal
      topic delivery of ovalbumin (OVA). A group was delivered of same volume
      physiological saline instated of OVA, C,D,E group were interfered by nasal
      delivery of LPS in different concentration (including LPS 20 ug, 10 ug, 5 ug per
      100 ul). Changes of nasal mucosa tissues and inflammatory cell infiltration were
      observed by HE staining, while neutrophil and eosinophil counted under high power
      microscope.Expression of IL-4, IFN-gamma, and IgE in nasal mucosa tissues were
      measured with immunohistochemical method.Realtime-PCR and Western-blot were used
      to evaluate the expression level of TLR-4 and NF-kappaB in nasal mucosa
      tissues.SPSS 13.0 software was used to analyze the data. RESULTS: Group B was
      observed to have developed AR injury of nasal mucosa. Eosinophil count and the
      expression of IL-4, IFN-gamma, and IgE were significantly higher in B group than
      those in A group (all P < 0.05), neutrophil count was significantly higher in C,
      D, E groups than that in B group (all P < 0.05). RESULTS: of immunohistochemical
      staining showed that, expression level of IFN-gamma, TLR-4 and NF-kappaB were
      significantly higher than group B (all P < 0.05), while IL-4 and IgE were
      significantly decreased than group B (all P < 0.05) . The protein expression of
      TLR-4 and NF-kappaB was 0.888 9 +/- 0.032 9 and 0.913 3 +/- 0.031 1 in group C,
      and 0.419 2 +/- 0.038 0 and 0.447 8 +/- 0.033 0 in group A, 0.616 1 +/- 0.025 1
      and 0.748 1 +/- 0.034 3 in group B, the difference was significant(all P < 0.05).
      CONCLUSIONS: TLR plays an important role of modulation between innate immunity
      and adaptive immunity in the pathogenesis of AR. The higher concentration of TLR
      doping may activate the higher expression of NF-kappaB then intervene the
      development of AR with immune deviation.

PMID- 24931017
TI  - [Effects of temporal fine structure stimulation on Mandarin identification in
      cochlear implant users].
AB  - OBJECTIVE: To assess the contribution of the temporal fine structure cues on
      speech recognition, especially tone perception of cochlear implant users whose
      native language is Mandarin Chinese. METHODS: Twelve Mandarin speaking users of
      the MED-EL COMBI 40+ cochlear implants with the standard COMBI 40+ electrode
      array participated in the study. The subjects were followed up and studied using
      the longitudinal method for six weeks to compare the difference in speech
      identification results between fine structure processing (FSP) and continuous
      interleaved sampler (CIS). The test battery comprised two objective speech tests,
      including tone identification in quiet as well as a sentence recognition task in
      quiet and noise. RESULTS: The scores of acute speech test: after replacing FSP
      strategy, the acute tone test results were similar to that of daily used CIS
      strategy(male version t = 0.791, P = 0.446;female version t = 0.679, P = 0.511),
      but the scores of MHINT were decreased significantly (t = -4.365, P = 0.001). The
      scores of long-lasting speech test were as follows the scores of tone
      identification test were sharply increased after subjects used the new coding
      strategy for six weeks continuously(male version t = 3.023, P = 0.018;female
      version t = 3.883, P = 0.003) and the MHIN results were similar to that of daily
      used CIS strategy(t = 1.475, P = 0.173). CONCLUSION: The extraction of temporal
      fine structure cues supplemented in speech processing strategy of cochlear
      implant benefits the improvements in tone perception and the understanding of
      speech in cochlear implant recipients, which can further promotes their quality
      of life.

PMID- 24931018
TI  - [Salvage surgery for neck recurrence or residue of nasopharyngeal carcinoma after
      primary radiotherapy].
AB  - OBJECTIVE: To investigate the surgical procedures and prognosis for neck
      recurrence or residue of nasopharyngeal carcinoma(NPC) after primary
      radiotherapy. METHODS: A total of 153 cases with neck recurrence or residue after
      radiotherapy in NPC who received salvage neck surgery between January 2001 and
      December 2011 were retrospectively analyzed. There were rN1 109 cases, rN2 17
      cases and rN3 27 cases. Of them 17 cases received bilateral neck dissection(ND)
      simultaneously. The surgical procedures included the modified radical neck
      dissection (MRND) in 66 cases, radical neck dissection (RND) in 48 cases,
      selective neck dissection(SND) in 28 cases, enlarged radical neck dissection
      (ERND) in 16 cases, local excision in 9 cases, and parotidectomy in 3 cases. The
      Kaplan-Meier method was used to calculate survival curves, and the differences
      between groups were calculated by chi(2) tests. RESULTS: There were 20 cases
      (13.1%) with lymph node(LN) metastasis in level I and 7 cases (4.6%) with parotid
      gland LN metastasis. The 3-year and 5-year overall survival rates were 57.2% and
      40.6% respectively, and the median survival time was 49 months. Cox regression
      analysis revealed that rN staging, size of LN and age were the main prognosis
      factors for survival. CONCLUSIONS: Salvage surgery was effective for neck
      recurrence or residue of NPC after primary treatment, and MRND and SND are
      reasonable options so as to improve functionality. Dissection of LN in level I
      and parotid gland should be selective. Patients with stage rN3 or LN > 6 cm or
      age > 50 years had poor prognosis.

PMID- 24931019
TI  - [Clinical analysis of 91 cases of primary parapharyngeal space tumors].
AB  - OBJECTIVE: To summarize and analyze the clinical features, diagnosis methods,
      surgical approaches and treatment outcomes of patients with primary
      parapharyngeal space tumors. METHODS: A retrospective review of 91 cases with
      primary parapharyngeal space tumors treated from January 1999 to December 2011
      was performed. All patients underwent preoperative enhanced CT scan and
      postoperative histopathologic examination. Intraoperative frozen section biopsies
      were performed in 36 of 91 cases. The surgical approaches included trans-cervical
      approach in 73 cases, trans-parotid approach in 5 cases, trans-oral approach in 5
      cases, and mandibulotomy in 8 cases. RESULTS: The postoperative pathological
      diagnoses consisted of 29 variants, including 20 for benign tumors and 9 for
      malignant tumors. Of the 80 cases with benign tumors, 6 cases were lost to follow
      up and 74 cases were followed up for 31-84 months with no recurrence. Eleven
      cases with malignant tumor were followed up for 8-51 months (median 29 months),
      of them 7 cases died and 1 case was lost to follow-up. The post-operative
      complications included Horner syndrome in 3 cases, hoarseness in 2 cases,
      hypoglossal nerve palsy in 1 case, accessory nerve palsy in 1 case, upper airway
      obstruction in 1 case, and internal carotid artery cavernous sinus fistula in 1
      case. CONCLUSIONS: Parapharyngeal space tumors are rare, with atypical clinical
      manifestation, and have pathological types of diversification. CT or MRI is
      helpful to evaluate the tumor size, location and possible sources, and to make
      operation scheme. Surgery is the first choice for parapharyngeal space tumors.
      Trans-cervical approach can be applied to most tumors. Parapharyngeal benign
      tumors have good prognosis, but malignant tumors have poor prognosis.

PMID- 24931020
TI  - [Characterization of scarred vocal fold regeneration after the intervention of
      extracellular matrix and human amniotic epithelial cells transplanting].
AB  - OBJECTIVE: To investigate the treatment for scarred vocal folds by transplanting
      human amniotic epithelial cells (hAECs)and injecting collagenase as well as
      hyaluronic acid (HA) for the intervention of the extracellular matrix(EMC), to
      observe the growth, distribution of hAECs and to assess the abilities of them for
      scarred vocal fold regeneration. METHODS: The lamina propria was injured by
      localized resection in thirty-eight vocal folds of twenty rabbits. hAECs were
      isolated from human amnion and marked by Lenti-GFP. After the formation of vocal
      fold scarring, hAECs were transplanted into ten vocal folds, collagenase and HA
      were injected into ten vocal folds, all three were injected into ten vocal folds,
      none were injected into eight vocal folds, and two normal vocal folds were used
      as control. At 1 month and 2 months after the transplanting, the survival, the
      distribution and the cytoactive of hAECs were examined by immunofluorescence
      method. Meanwhile, at 1 month, 2 months, 3 months and 6 months after the
      operation, HE staining was performed for histopathological research, Masson
      trichrome staining and immunohistochemical staining were used for collagen and
      fibronectin respectively. RESULTS: After implanted into the scarred vocal folds,
      hAECs could survive in vocal fold lamina propria for two months. The
      immunofluorescence analysis showed the cytoactive of hAECs.Six months
      postoperatively, compared with that in the normal vocal folds, collagen in the
      untreated scarred vocal folds more increased and disorderly distributed; the
      changes in other three groups were between the two groups above, but the group
      injected with all of hAECs, collagenase and HA was better than other two groups.
      Besides, the mean density of fibronectin in the scarred untreated control group
      was more significantly increased than that in the normal vocal folds; the changes
      in other three groups were between the two groups above, but the group injected
      with all of hAECs, collagenase and HA was better than other two groups.
      CONCLUSION: The transplanting of hAECs and the interventions of EMC by injecting
      collagenase as well as HA have better abilities in rabbit scarred vocal fold
      reparation and regeneration by promoting ECM secretion, rational distribution and
      part ordering arrangement.

PMID- 24931021
TI  - [Metformin inhibits the proliferation of hypopharyngeal carcinoma Fadu cells and
      enhances the chemotherapeutic sensitivity of cells].
AB  - OBJECTIVE: To investigate the role of metformin on the growth inhibition induced
      by chemotherapeutic agents in hypopharyngeal carcinoma Fadu cells. METHODS: Fadu
      cells were treated with different concentrations of metformin for different time
      or treated with different concentrations of cisplatin, 5-fluorouracil or
      paclitaxel with or without metformin 5 mmol/L. MTT assay was used to evaluate the
      influence of metformin on the proliferation of Fadu cells. Cell-cycle was
      analyzed by flow cytometry. The expressions of AMP-dependent/activated protein
      kinase (AMPK) and P21 were examined by immunocytochemistry. RESULTS: Metformin
      inhibited the proliferation of Fadu cells in a dose-and time-dependent
      manner.Flow cytometry showed that cell cycle arrest in G1 phase was induced by
      metformin in Fadu cells.Immunocytochemistry showed the expressions of both AMPK
      and P21 in cells treated with metformin were higher than those in cells untreated
      with metformin. The growth inhibition of cells induced by cisplatin or paclitaxel
      but not 5-fluorouracil was enhanced by metformin. The combined indexes of
      cisplatin/paclitaxel/5-fluorouracil and metformin for 48 h were 0.43, 0.37, and
      1.15, respectively. CONCLUSIONS: Metformin may inhibit the proliferation of Fadu
      cells by inducing the cell cycle arrest in G1 phase mediated in part by AMPK and
      P21. Metformin enhances the sensitivity of Fadu cells to cisplatin and
      paclitaxel.

PMID- 24931022
TI  - [Noninvasive measurement of nasal NO and fractional exhaled NO in healthy people
      and patients with allergic rhinitis].
AB  - OBJECTIVE: To measure the nasal nitric oxide (NNO) and fractional exhaled nitric
      oxide (FENO) in healthy people and patients with allergic rhinitis (AR), and to
      discuss the clinical significance of the results. METHODS: Ninety-six healthy
      volunteers and 51 patients with moderate-severe persistent AR, but without
      asthma, were enrolled. NNO and FENO concentrations were measured noninvasively by
      using of NIOX MINO (Aerocrine AB, Solna, Sweden).SPSS 13.0 software was used to
      analyze the data. RESULTS: The concentration of NNO in healthy people was 245.0
      [189.8;331.3] ppb (median [25th percentile; 75th percentile], the followings were
      same as). The concentration of FENO was 14.0 [10.0; 18.0] ppb. The concentration
      of NNO in patients with AR was 304.0[179.5; 397.5]ppb. The concentration of FENO
      was 21.0 [16.0; 40.5] ppb. The concentration of NNO in the AR patients was higher
      than that in the healthy persons, but the difference did not reach statistical
      significance (Z = 1.349, P = 0.177).On the other hand, FENO concentrations were
      significantly increased in patients compared with concentrations in healthy
      persons (Z = 5.555, P = 0.000). CONCLUSIONS: FENO concentrations of patients with
      moderate-severe persistent AR are increased significantly even though the
      patients do not have typical symptoms of asthma. This finding suggests that AR
      patients should be treated actively in order to prevent asthma from developing in
      them.

PMID- 24931024
TI  - [Misdiagnosis of branchio-oto-renal syndrome as preauricular fistula: report of
      two cases].

PMID- 24931023
TI  - [Inhibition of Hep-2 cell apoptosis after annexin A5 knockdown].
AB  - OBJECTIVE: To study the effect of annexin A5 on the apoptosis of laryngeal cancer
      cells. METHODS: Special siRNAs were used to knock annexinA5 down in Hep-2 cell,
      and RT-PCR and Western blot were applied to identify the efficacy of RNA
      interference. The flow cytometry assay was performed to detect the Hep-2 cell
      apoptosis. RESULTS: RT-PCR analysis showed that the relative mRNA expression of
      annexin A5 in siRNA group, negative control group, Lipofectamine 2000 group and
      blank control group were 0.70 +/- 0.03, 1.18 +/- 0.05, 1.17 +/- 0.06 and 1.23 +/-
      0.07. The relative mRNA expression of annexin A5 in siRNA group was significantly
      decreased than contrast groups(t = -14.77, t = -13.23, t = -12.99, P < 0.05).In
      Western blot assay, the trend of protein expression level was consistent with the
      mRNA expression levels of annexin A5. The relative levels of proteins in siRNA
      group, negative control group, Lipofectamine 2000 group and blank control group
      were shown 1.21 +/- 0.03, 3.88 +/- 0.06, 3.87 +/- 0.02 and 3.95 +/- 0.08. The
      relative protein expression of annexin A5 in siRNA group was significantly
      decreased than contrast groups(t = -70.34, t = -150.62, t = -56.32, P < 0.05). At
      the same time in flow cytometry the apoptotic rate of siRNA group, negative
      control group, Lipofectamine 2000 group and blank control group were 4.43% +/-
      0.12%, 13.67% +/- 0.22%, 13.66% +/- 0.12% and 13.35% +/- 0.13%, the difference
      between the siRNA group and contrast groups was statistically significant(t = 
      62.50, t = -14.16, t = -11.47, P < 0.05).So after RNA interference, expression of
      annexin A5 decreased, and the results in the apoptosis inhibition of Hep-2 cell.
      CONCLUSION: Annexin A5 promotes apoptosis of Hep-2 cells, and it may be a
      potential therapeutic target for the laryngeal cancer.

PMID- 24931025
TI  - [Laryngeal chondrosarcoma in a case].

PMID- 24931026
TI  - [Right-sided congenital piriform sinus fistulae in two adults].

PMID- 24931027
TI  - [The combination therapy for allergic rhinitis].

PMID- 24931028
TI  - [Clinical significance of nasal exhaled nitric oxide measurement].

PMID- 24931029
TI  - [Pathophysiology, diagnosis and treatment of allergic rhinitis].

PMID- 24931030
TI  - [Hemangioma of the bone in inferior nasal concha:a case report].

PMID- 24931031
TI  - Pre-transplant immune state defined by serum markers and alloreactivity predicts
      acute rejection after living donor kidney transplantation.
AB  - Acute rejection (AR) remains a major cause for long-term kidney allograft
      failure. Reliable immunological parameters suitable to define the pre-transplant
      immune state and hence the individual risk of graft rejection are highly desired
      to preferably adapt the immunosuppressive regimen in advance. Donor and third
      party alloreactivities were determined by mixed lymphocyte cultures. Soluble
      forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various
      lymphocyte subpopulations were measured using flow cytometry. All patients
      received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and
      were grouped according to biopsy results within the first year: rejection-free
      (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients
      with AR showed the highest pre-transplant alloreactivities and serum levels
      (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum
      analysis only, multivariate logistic regression (logit link function) yielded a
      prognostic score for prediction of rejection with 75.0% sensitivity and 69.2%
      specificity. Patients with rejection showed markedly higher pre-transplant
      frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+)
      CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune
      state defined by alloreactivity, serum markers, and particular lymphocyte subsets
      seems to correlate with occurrence of graft rejection after kidney
      transplantation. A prognostic score based on pre-transplant serum levels has
      shown great potential for prediction of rejection episodes and should be further
      evaluated. 

PMID- 24931032
TI  - Brain changes underlying cognitive dysfunction in diabetes: what can we learn
      from MRI?
AB  - Diabetes is associated with cognitive dysfunction and an increased risk of
      dementia. This article addresses findings with brain MRI that may underlie
      cognitive dysfunction in diabetes. Studies in adults with type 1 diabetes show
      regional reductions in brain volume. In those with a diabetes onset in childhood,
      these volume reductions are likely to reflect the sum of changes that occur
      during brain development and changes that occur later in life due to exposure to
      diabetes-related factors. Type 2 diabetes is associated with global brain atrophy
      and an increased burden of small-vessel disease. These brain changes occur in the
      context of aging and often also in relation to an adverse vascular risk factor
      profile. Advanced imaging techniques detect microstructural lesions in the
      cerebral gray and white matter of patients with diabetes that affect structural
      and functional connectivity. Challenges are to further unravel the etiology of
      these cerebral complications by integrating findings from different imaging
      modalities and detailed clinical phenotyping and by linking structural MRI
      abnormalities to histology. A better understanding of the underlying mechanisms
      is necessary to establish interventions that will improve long-term cognitive
      outcomes for patients with type 1 and type 2 diabetes. 

PMID- 24931033
TI  - Inflammation, defective insulin signaling, and mitochondrial dysfunction as
      common molecular denominators connecting type 2 diabetes to Alzheimer disease.
AB  - A growing body of evidence supports an intriguing clinical/epidemiological
      connection between Alzheimer disease (AD) and type 2 diabetes (T2D). T2D patients
      have significantly increased risk of developing AD and vice versa. Recent studies
      have begun to reveal common pathogenic mechanisms shared by AD and metabolic
      disorders, notably obesity and T2D. In T2D and obesity, low-grade chronic
      inflammation is a key mechanism leading to peripheral insulin resistance, which
      progressively causes tissue deterioration and overall health decline. In the
      brain, proinflammatory signaling was recently found to mediate impaired neuronal
      insulin signaling, synapse deterioration, and memory loss. Here, we review
      evidence indicating that inflammation, insulin resistance, and mitochondrial
      dysfunction are common features in AD and T2D. We further propose the hypothesis
      that dementia and its underlying neuronal dysfunction are exacerbated or driven
      by peripheral inflammation. Identification of central and peripheral inflammation
      as potential mediators of brain dysfunction in AD may lead to the development of
      effective treatments for this devastating disease. 

PMID- 24931036
TI  - Rechargeable batteries with high energy storage activated by in-situ induced
      fluorination of carbon nanotube cathode.
AB  - High performance rechargeable batteries are urgently demanded for future energy
      storage systems. Here, we adopted a lithium-carbon battery configuration. Instead
      of using carbon materials as the surface provider for lithium-ion adsorption and
      desorption, we realized induced fluorination of carbon nanotube array (CNTA)
      paper cathodes, with the source of fluoride ions from electrolytes, by an in-situ
      electrochemical induction process. The induced fluorination of CNTA papers
      activated the reversible fluorination/defluorination reactions and lithium-ion
      storage/release at the CNTA paper cathodes, resulting in a dual-storage
      mechanism. The rechargeable battery with this dual-storage mechanism demonstrated
      a maximum discharging capacity of 2174 mAh (gcarbon)(-1) and a specific energy of
      4113 Wh kg(carbon)(-1) with good cycling performance.

PMID- 24931035
TI  - Repurposing diabetes drugs for brain insulin resistance in Alzheimer disease.
AB  - A growing body of clinical and epidemiological research suggests that two of the
      most common diseases of aging, type 2 diabetes (T2DM) and Alzheimer disease (AD),
      are linked. The nature of the association is not known, but this observation has
      led to the notion that drugs developed for the treatment of T2DM may be
      beneficial in modifying the pathophysiology of AD and maintaining cognitive
      function. Recent advances in the understanding of the biology of T2DM have
      resulted in a growing number of therapies that are approved or in clinical
      development for this disease. This review summarizes the evidence that T2DM and
      AD are linked, with a focus on the cellular and molecular mechanisms in common,
      and then assesses the various clinical-stage diabetes drugs for their potential
      activity in AD. At a time when existing therapies for AD offer only limited
      symptomatic benefit for some patients, additional clinical trials of diabetes
      drugs are needed to at least advance the care of T2DM patients at risk for or
      with comorbid AD and also to determine their value for AD in general. 

PMID- 24931037
TI  - Fungal biology: ECM fungi and all that JAZz.

PMID- 24931034
TI  - Insulin action in brain regulates systemic metabolism and brain function.
AB  - Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling
      partners, are distributed throughout the brain. Insulin acts on these receptors
      to modulate peripheral metabolism, including regulation of appetite, reproductive
      function, body temperature, white fat mass, hepatic glucose output, and response
      to hypoglycemia. Insulin signaling also modulates neurotransmitter channel
      activity, brain cholesterol synthesis, and mitochondrial function. Disruption of
      insulin action in the brain leads to impairment of neuronal function and
      synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau
      protein, an early component in the development of Alzheimer disease. Thus,
      alterations in insulin action in the brain can contribute to metabolic syndrome,
      and the development of mood disorders and neurodegenerative diseases. 

PMID- 24931041
TI  - Parasite biology: A tripartite virulence complex in Toxoplasma.

PMID- 24931045
TI  - The impact of diagnostic imaging wait times on the prognosis of lung cancer.
AB  - OBJECTIVE: This study was performed to determine whether gaps in patient flow
      from initial lung imaging to computed tomography (CT) guided lung biopsy in
      patients with non-small cell lung cancer (NSCLC) was associated with a change in
      tumour size, stage, and thus prognosis. METHODS: All patients who had a CT-guided
      lung biopsy in 2009 (phase I) and in 2011 (phase II) with a pathologic diagnosis
      of primary lung cancer (NSCLC) at Eastern Health, Newfoundland, were identified.
      Dates of initial abnormal imaging, confirmatory CT (if performed), and CT-guided
      biopsy were recorded, along with tumour size and resulting T stage at each time
      point. In 2010, wait times for diagnostic imaging at Eastern Health were reduced.
      The stage and prognosis of NSCLC in 2009 was compared with 2011. RESULTS: In
      phase 1, there was a statistically significant increase in tumour size (mean
      difference, 0.67 cm; P < .0001) and stage (P < .0001) from initial image to
      biopsy. There was a moderate correlation between the time (in days) between the
      images and change in size (r = 0.33, P = .008) or stage (r = 0.26, P = .036). In
      phase II, the median wait time from initial imaging to confirmatory CT was
      reduced to 7.5 days (from 19 days). At this reduced wait time, there was no
      statistically significant increase in tumour size (mean difference, 0.02; P >
      .05) or stage (P > .05) from initial imaging to confirmatory CT. CONCLUSIONS:
      Delays in patient flow through diagnostic imaging resulted in an increase in
      tumour size and stage, with a negative impact on prognosis of NSCLC. This
      information contributed to the hiring of additional CT technologists and extended
      CT hours to decrease the wait time for diagnostic imaging. With reduced wait
      times, the prognosis of NSCLC was not adversely impacted as patients navigated
      through diagnostic imaging.

PMID- 24931042
TI  - Functional long-range RNA-RNA interactions in positive-strand RNA viruses.
AB  - Positive-strand RNA viruses are important human, animal and plant pathogens that
      are defined by their single-stranded positive-sense RNA genomes. In recent years,
      it has become increasingly evident that interactions that occur between distantly
      positioned RNA sequences within these genomes can mediate important viral
      activities. These long-range intragenomic RNA-RNA interactions involve direct
      nucleotide base pairing and can span distances of thousands of nucleotides. In
      this Review, we discuss recent insights into the structure and function of these
      intriguing genomic features and highlight their diverse roles in the gene
      expression and genome replication of positive-strand RNA viruses. 

PMID- 24931046
TI  - Benign lesions that mimic thyroid malignancy on ultrasound.

PMID- 24931043
TI  - Motility and more: the flagellum of Trypanosoma brucei.
AB  - Trypanosoma brucei is a pathogenic unicellular eukaryote that infects humans and
      other mammals in sub-Saharan Africa. A central feature of trypanosome biology is
      the single flagellum of the parasite, which is an essential and multifunctional
      organelle that facilitates cell propulsion, controls cell morphogenesis and
      directs cytokinesis. Moreover, the flagellar membrane is a specialized subdomain
      of the cell surface that mediates attachment to host tissues and harbours
      multiple virulence factors. In this Review, we discuss the structure, assembly
      and function of the trypanosome flagellum, including canonical roles in cell
      motility as well as novel and emerging roles in cell morphogenesis and host
      parasite interactions. 

PMID- 24931044
TI  - The elemental composition of virus particles: implications for marine
      biogeochemical cycles.
AB  - In marine environments, virus-mediated lysis of host cells leads to the release
      of cellular carbon and nutrients and is hypothesized to be a major driver of
      carbon recycling on a global scale. However, efforts to characterize the effects
      of viruses on nutrient cycles have overlooked the geochemical potential of the
      virus particles themselves, particularly with respect to their phosphorus
      content. In this Analysis article, we use a biophysical scaling model of intact
      virus particles that has been validated using sequence and structural information
      to quantify differences in the elemental stoichiometry of marine viruses compared
      with their microbial hosts. By extrapolating particle-scale estimates to the
      ecosystem scale, we propose that, under certain circumstances, marine virus
      populations could make an important contribution to the reservoir and cycling of
      oceanic phosphorus. 

PMID- 24931047
TI  - Intra-abdominal solid organ injuries: an enhanced management algorithm.
AB  - The organ injury scale grading system proposed by the American Association for
      the Surgery of Trauma provides guidelines for operative versus nonoperative
      management in solid organ injuries; however, major shortcomings of the American
      Association for the Surgery of Trauma injury scale may become apparent with low
      grade injuries, in which conservative management may fail. Nonoperative
      management of common intra-abdominal solid organ injuries relies increasingly on
      computed tomographic findings and other clinical factors, including patient age,
      presence of concurrent injuries, and serial clinical assessments. Familiarity
      with characteristic imaging features is essential for the prompt diagnosis and
      appropriate treatment of blunt abdominal trauma. In this pictorial essay, the
      spectrum of the American Association for the Surgery of Trauma organ injury scale
      grading system is illustrated, and a multidisciplinary management algorithm for
      common intra-abdominal solid organ injuries is proposed. 

PMID- 24931048
TI  - Facile base-free in situ generation and palladation of mesoionic and normal N
      heterocyclic carbenes at ambient conditions.
AB  - Synthesis of normal and mesoionic N-heterocyclic carbene Pd(II) complexes in near
      quantitative yields from the corresponding NHC precursor salts under base free
      and ambient conditions is reported. A plausible mechanism involving charge
      assisted hydrogen bonded intermediates is proposed.

PMID- 24931049
TI  - Contrast-dependent OFF-dominance in cat primary visual cortex facilitates
      discrimination of stimuli with natural contrast statistics.
AB  - Both theoretical and experimental studies suggest that response properties in the
      visual system are shaped by signals in the natural environment. Recent studies
      showed that, in the primary visual cortex (V1), neurons preferring light
      decrements (OFF stimuli) outnumber those preferring light increments (ON
      stimuli). However, it is not clear whether the OFF-dominance in V1 neurons is
      related to the contrast statistics in natural images. By analysing the
      distribution of negative and positive contrasts in natural images at several
      spatial scales, we showed that optimal coding of the natural contrast signals
      would lead to a contrast-dependent OFF-dominant response, with a stronger degree
      of OFF-dominance at a higher contrast. Using bright and dark stimuli at various
      contrast levels to measure the receptive fields of neurons in cat V1, we found an
      increasing degree of OFF-dominance of the neuronal population as the contrast was
      increased. By modeling receptive fields exhibiting OFF- and ON-dominance, we
      found that contrast-dependent OFF-dominance facilitated the discrimination of
      stimuli with natural contrast distribution. Thus, by matching contrast-dependent
      OFF-dominance to the statistics of contrast distribution in natural images, V1
      neurons may better discriminate contrast information in natural scenes. 

PMID- 24931050
TI  - Lyotropic liquid crystal for long-term delivery of peptide drugs.

PMID- 24931051
TI  - Estimating the development of the fennel aphid, Hyadaphis foeniculi (Passerini)
      (Hemiptera: Aphiididae), using non-linear models.
AB  - BACKGROUND: Non-linear models making it possible to predict agricultural pest
      outbreaks and optimise control tactics are of primary importance for integrated
      pest management. The development period for immature stages of the fennel aphid
      Hyadaphis foeniculi (Passerini) (Hemiptera: Aphididae) at constant temperatures
      was modelled in order to determine mathematical functions for simulating the
      aphid's development. Non-linear models were used to describe the relationship
      between temperature and development rates of H. foeniculi subjected to constant
      temperatures. RESULTS: The models used were found to be good fits for estimating
      H. foeniculi development rates as a function of temperature, with the exception
      of the Davidson model. The development time of H. foeniculi nymphs ranged from
      2.73 days (first instar) to 6.18 days (fourth instar) at 15  degrees C, from 2.57
      days (first instar) to 4.52 days (fourth instar) at 20  degrees C and from 1.53
      days (first instar) to 2.05 days (fourth instar) at 28  degrees C. CONCLUSION:
      These models provide important tools for better elucidation of the relationship
      between temperature and development rates in H. foeniculi. The results could be
      used for predicting the occurrence of the various immature stages of H. foeniculi
      in the fennel crop in Brazil, making it possible to predict more accurately the
      best periods for implementing pest control.

PMID- 24931052
TI  - Disposable surface plasmon resonance aptasensor with membrane-based sample
      handling design for quantitative interferon-gamma detection.
AB  - ELISA and ELISPOT methods are utilized for interferon-gamma (IFN-gamma) release
      assays (IGRAs) to detect the IFN-gamma secreted by T lymphocytes. However, the
      multi-step protocols of the assays are still performed with laboratory
      instruments and operated by well-trained people. Here, we report a membrane-based
      microfluidic device integrated with a surface plasmon resonance (SPR) sensor to
      realize an easy-to-use and cost effective multi-step quantitative analysis. To
      conduct the SPR measurements, we utilized a membrane-based SPR sensing device in
      which a rayon membrane was located 300 MUm under the absorbent pad. The basic
      equation covering this type of transport is based on Darcy's law. Furthermore,
      the concentration of streptavidin delivered from a sucrose-treated glass pad
      placed alongside the rayon membrane was controlled in a narrow range (0.81 MUM +/
      6%). Finally, the unbound molecules were removed by a washing buffer that was
      pre-packed in the reservoir of the chip. Using a bi-functional, hairpin-shaped
      aptamer as the sensing probe, we specifically detected the IFN-gamma and
      amplified the signal by binding the streptavidin. A high correlation coefficient
      (R(2) = 0.995) was obtained, in the range from 0.01 to 100 nM. A detection limit
      of 10 pM was achieved within 30 min. Thus, the SPR assay protocols for IFN-gamma
      detection could be performed using this simple device without an additional
      pumping system. 

PMID- 24931054
TI  - In vivo administration of TLR9 agonist reduces the severity of experimental
      autoimmune encephalomyelitis. The role of plasmacytoid dendritic cells and B
      lymphocytes.

PMID- 24931053
TI  - Ecological impact of MCB3837 on the normal human microbiota.
AB  - MCB3837 is a novel, water-soluble, injectable prodrug that is rapidly converted
      to the active substance MCB3681 in vivo following intravenous (i.v.)
      administration. Both MCB3837 and MCB3681 are oxazolidinone-quinolone hybrid
      molecules. The purpose of the present study was to investigate the effect of
      MCB3681 on the human skin, nose, oropharyngeal and intestinal microbiota
      following administration of MCB3837. Twelve healthy male subjects received i.v.
      MCB3837 (6 mg/kg body weight) once daily for 5 days. Skin, nose, saliva and
      faecal samples were collected on Day -1 (pre dose), during administration on Days
      2 and 5, and post dose on Days 8, 12 and 19. Micro-organisms were identified to
      genus level. No measurable concentrations of MCB3681 were found in any saliva
      samples or in the faecal samples on Day -1. On Day 2, 10 volunteers had faecal
      MCB3681 concentrations between 16.5 mg/kg faeces and 275.1mg/kg faeces; no
      MCB3681 in faeces could be detected in two of the volunteers. On Day 5, all
      volunteers had faecal concentrations of MCB3681 ranging from 98.9 to 226.3 mg/kg.
      MCB3681 caused no ecological changes in the skin, nasal and oropharyngeal
      microbiota. The numbers of enterococci, bifidobacteria, lactobacilli and
      clostridia decreased in the intestinal microbiota during administration of the
      drug. Numbers of Escherichia coli, other enterobacteria and Candida were not
      affected during the study. There was no impact on the number of Bacteroides. The
      faecal microbiota was normalised on Day 19. No new colonising aerobic or
      anaerobic Gram-positive bacteria with MCB3681 minimum inhibitory concentrations
      of >=4 mg/L were found.

PMID- 24931055
TI  - Dietary self-monitoring and long-term success with weight management.
AB  - OBJECTIVE: To examine the contributions of frequency, consistency, and
      comprehensiveness of dietary self-monitoring to long-term weight change. METHODS:
      Participants included 220 obese women (mean +/- SD, age = 59.3 +/- 6.1 years; BMI
      = 36.8 +/- 4.9 kg/m(2) ) who achieved a mean weight loss of -10.39 +/- 5.28% from
      baseline during 6 months of behavioral treatment and regained 2.30 +/- 7.28%
      during a 12-month extended-care period. The contributions of cumulative frequency
      of self-monitoring (total number of food records), consistency across time
      (number of weeks with >=3 records), and comprehensiveness of information recorded
      were examined as predictors of weight regain in a hierarchical linear regression
      analysis. The mediating role of adherence to daily caloric intake goals was
      tested using a bootstrapping analysis. RESULTS: The association between high
      total frequency of self-monitoring and reduced weight regain was moderated by
      weekly consistency of self-monitoring, P = 0.004; increased frequency produced
      beneficial effects on weight change only when coupled with high consistency (>3
      days/week). There was no impact of comprehensiveness on weight change, P > 0.05.
      The favorable effect of high frequency/high consistency self-monitoring on weight
      change was partially mediated by participants' success in meeting daily caloric
      intake goals (P < 0.001). CONCLUSION: The combination of high frequency plus high
      consistency of dietary self-monitoring improves long-term success in weight
      management.

PMID- 24931056
TI  - Studies on distribution of alpha1-antitrypsin, lysozyme, lactoferrin, and mast
      cell enzymes in diseased middle ear mucosa.
AB  - CONCLUSION: Antimicrobial agents (AMAs) and mast cells in chronic otitis media
      (COM) may play a protective role in the pathogenesis of COM. Among them, our
      results indicated that lysozyme may be the most important parameter of the mucosa
      infectivity in COM. OBJECTIVES: AMAs include alpha 1-antitrypsin (alpha1-AT),
      lysozyme, and lactoferrin and exhibit innate immune activity that is known to
      play a critical role in mucosal defenses. In addition, proteases expressed in
      mast cells contribute to mucosal defenses. The aim of this study was to identify
      AMAs responsible for COM as well as their association with middle ear mucosal
      diseases. METHODS: Middle ear mucosa (MEM) was intraoperatively collected by
      biopsy from patients, diagnosed as COM without or with cholesteatoma, and
      immediately processed for immunohistochemical study to evaluate expression of
      AMAs and mast cell proteases (chymase and tryptase). RESULTS: The AMAs and mast
      cell enzymes were observed prominently in the chronic middle ear diseases whereas
      immunoreactivity of alpha1-AT and lysozyme was not significantly increased in the
      COM with cholesteatoma compared with that in COM without cholesteatoma.
      Lactoferrin was not detected in the diseased MEMs.

PMID- 24931057
TI  - Prescription opioid abuse and tampering in the United States: results of a self
      report survey.
AB  - OBJECTIVE: The objective of this study is to estimate the prevalence and impact
      of prescription opioid abuse and tampering among US adults. METHODS: Participants
      from the US National Health and Wellness Survey were invited to complete an
      online survey assessing use, misuse, and abuse of prescription opioid medications
      in the preceding 3 months. A total of 25,864 adults were screened for self
      reported opioid abuse. Prevalence was calculated using weights based on age,
      gender, race, and education. Respondents reporting abuse or medical use of
      prescription opioid medication in the prior 3 months (N = 1,242) completed a
      questionnaire assessing health care resource use and the Work Productivity and
      Activity Impairment questionnaire. RESULTS: The prevalence of prescription opioid
      abuse in the 3 months prior to the survey was estimated at 1.31% of US adults,
      with approximately half (0.67%) tampering during that time. Opioid abuse
      increased with younger age, male sex, minority race, psychiatric illness,
      alcoholism, cigarette smoking, being employed, and higher household income.
      Respondents abusing opioid medications reported greater impairment in work and
      nonwork activities and more health care use than nonusers. Tampering with opioid
      medication was associated with greater productivity loss and increased use of
      health care (all P < 0.05). CONCLUSIONS: Tampering with opioid medications to get
      high is associated with substantial loss of productivity and health care use.
      Technologies that reduce users' ability to tamper may reduce the burden of opioid
      abuse on the health care system.

PMID- 24931058
TI  - The role of the central Fe atom in the N4-macrocyclic structure for the
      enhancement of oxygen reduction reaction in a heteroatom nitrogen-carbon
      nanosphere.
AB  - In the present work, we demonstrated the significance of a central transition
      metal, Fe, in a N4-macrocycle for the enhancement of ORR activity and other
      electrochemical properties. The catalysts were synthesized by a solution plasma
      process. Fe-phthalocyanine/benzene and phthalocyanine/benzene were chosen as the
      precursors of Fe-phthalocyanine based mesoporous carbon (FP-MCS) and
      phthalocyanine based mesoporous carbon (P-MCS) catalysts, respectively. The
      existence of Fe-N4 and N4 macrocyclic structures was confirmed by X-ray
      photoelectron spectroscopy. From the chemical bonding structure, FP-MCS
      demonstrated that the Me-N peaks increased as the amount of iron-phthalocyanine
      introduced in the experiment increased. The dominant active site was shifted from
      pyridinic nitrogen to Me-N when iron-phthalocyanine was present. The analysis of
      Tof-SIMS indicated that the relative intensity of FeN4Cy(+) ions was
      approximately 50% of the total amount of ionized species of ?FeNxCy(+). Both XPS
      and Tof-SIMS results confirmed that the Fe-N4 site was the most favourable
      structure in the matrix. From CV measurements, the cathodic peak current
      corresponding to ORR activity slightly shifted from -0.19 V to -0.17 V when the
      active site changed from N4 to Fe-N4 macrocyclic structure. The current density
      increased more than 30% in the presence of iron. Based on the calculation of
      Koutecky-Levich plots, the electron transfer numbers for ORR reaction in P- and
      FP-MCSs were 3.25 and 3.98, respectively. These results clearly demonstrated that
      the presence of a Fe central ion in the N4-macrocyclic structure significantly
      enhanced the ORR and charge transfer number in ORR activities. 

PMID- 24931060
TI  - Template-assisted in situ polymerization for forming blue organic light-emitting
      nanotubes.
AB  - A functional monomer was thermally polymerized inside the anodized aluminum oxide
      (AAO) channel into nanotubes, which were isolated and characterized to be
      semiconductive and blue fluorescent, and were utilized as nano-containers of
      Fe3O4 nanoparticles to form magnetic nanocomposites. 

PMID- 24931059
TI  - Calling for rapid development of a safe and effective MERS vaccine.
AB  - The geographic spread and rapid increase in the cases of Middle East respiratory
      syndrome (MERS) caused by a novel coronavirus (MERS-CoV) during the past two
      months have raised concern about its pandemic potential. Here we call for the
      rapid development of an effective and safe MERS vaccine to control the spread of
      MERS-CoV. 

PMID- 24931062
TI  - Is thrombophilia associated with placenta-mediated pregnancy complications? A
      prospective cohort study: reply.

PMID- 24931063
TI  - Extensive ecchymosis associated with infective endocarditis.

PMID- 24931061
TI  - Metabolic syndrome-like components and prostate cancer risk: results from the
      Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study.
AB  - OBJECTIVE: To evaluate the relationship between number of metabolic syndrome
      (MetS)-like components and prostate cancer diagnosis in a group of men where
      nearly all biopsies were taken independent of prostate-specific antigen (PSA)
      level, thus minimising any confounding from how the various MetS-like components
      may influence PSA levels. SUBJECTS/PATIENTS AND METHODS: We analysed data from
      6426 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study
      with at least one on-study biopsy. REDUCE compared dutasteride vs placebo on
      prostate cancer risk among men with an elevated PSA level and negative pre-study
      biopsy and included two on-study biopsies regardless of PSA level at 2 and 4
      years. Available data for MetS-like components included data on diabetes,
      hypertension, hypercholesterolaemia, and body mass index. The association between
      number of these MetS-like components and prostate cancer risk and low-grade
      (Gleason sum <7) or high-grade (Gleason sum >7) vs no prostate cancer was
      evaluated using logistic regression. RESULTS: In all, 2171 men (34%) had one MetS
      like component, 724 (11%) had two, and 163 (3%) had three or four. Men with more
      MetS-like components had lower PSA levels (P = 0.029). One vs no MetS-like
      components was protective for overall prostate cancer (P = 0.041) and low-grade
      prostate cancer (P = 0.010). Two (P = 0.69) or three to four (P = 0.15) MetS-like
      components were not significantly related to prostate cancer. While one MetS-like
      component was unrelated to high-grade prostate cancer (P = 0.97), two (P = 0.059)
      or three to four MetS-like components (P = 0.02) were associated with increased
      high-grade prostate cancer risk, although only the latter was significant.
      CONCLUSION: When biopsies are largely PSA level independent, men with an initial
      elevated PSA level and a previous negative biopsy, and multiple MetS-like
      components were at an increased risk of high-grade prostate cancer, suggesting
      the link between MetS-like components and high-grade prostate cancer is unrelated
      to a lowered PSA level.

PMID- 24931064
TI  - Use of the CRUSADE bleeding risk score in the prediction of major bleeding for
      patients with acute coronary syndrome receiving enoxaparin in Thailand.
AB  - BACKGROUND: CRUSADE risk score stands out as a simple-to-use bleeding risk model.
      However, its use is still doubtful for Thai population. The aim of this study was
      to assess the prognostic value of CRUSADE in predicting risk of major bleeding
      among Thai patients with acute coronary syndrome (ACS) receiving enoxaparin.
      METHODS: A retrospective cohort study was performed using patients with ACS who
      were hospitalised at a university hospital in Bangkok between 2006 and 2009 and
      had received enoxaparin. The CRUSADE risk score was calculated. The model
      validation was tested by using C statistic and Hosmer-Lemeshow goodness-of-fit.
      RESULTS: The overall incidence of major bleeding was 18.3%. Median CRUSADE score
      for entire study population, unstable angina (UA), non-ST elevation myocardial
      infarction (NSTEMI), and ST elevation myocardial infarction (STEMI) were 49, 47,
      53, and 39, respectively. Hosmer-Lemeshow goodness of fit revealed no statistical
      significance in all groups. The CRUSADE model demonstrated a satisfactory
      discriminatory capacity for the entire study population (C = 0.688), UA (C =
      0.591), NSTEMI (C = 0.693), and STEMI groups (C = 0.736). CONCLUSIONS: Across the
      ACS spectrum, CRUSADE risk score was able to estimate in-hospital major bleeding
      of Thai patients with ACS who received treatment with enoxaparin. The application
      of these results in Thailand may be helpful in the identification of patients at
      high bleeding risk and also may lead to implementation of appropriate prevention.

PMID- 24931065
TI  - Post-traumatic injury of the brachiocephalic artery: on-pump beating heart
      repair.
AB  - We report the case of 54 year-old man who presented with an injury of the
      brachiocephalic artery secondary to a violent blunt chest trauma. The patient
      underwent urgent open surgical repair. The procedure was achieved on on-pump
      beating heart approach. The subsequent course was uneventful. 

PMID- 24931066
TI  - Differences in exercise capacity in patients with chronic left heart failure and
      chronic right heart failure.
AB  - BACKGROUND: Exercise impairment is common in chronic left heart failure and
      pulmonary arterial hypertension (PAH). Exercise impairment degree is a strong
      predictor of clinical outcome. Our purpose was to evaluate differences in
      exercise capacity using cardiopulmonary exercise testing (CPX) in patients with
      chronic left and right heart failure, and determine which factors were related to
      exercise impairment. METHODS: 102 patients with class II/III New York Heart
      Association were involved in the study (41 with chronic left heart failure, 61
      with chronic right heart failure secondary to PAH). All patients underwent CPX to
      evaluate exercise capacity. RESULTS: Patients with right heart failure had
      significantly lower peak oxygen uptake (VO2), peak VO2/kg ratio, peak oxygen
      uptake/heart rate (VO2/HR) ratio and increases in oxygen uptake/increase in work
      rate (DeltaVO2/DeltaWR) slope, and had higher minute ventilation/CO2 production
      ratio and peak dead space volume/tidal volume during exercise. In patients with
      left heart failure, peak VO2/HR ratio was positively correlated with
      DeltaVO2/DeltaWR slope. However, VO2 and VO2/HR ratio were positively correlated
      with DeltaVO2/DeltaWR slope in patients with right heart failure. CONCLUSIONS:
      Compared with left heart failure, patients with right heart failure showed worse
      exercise capacity resulting from worse pulmonary and cardiovascular adaptation to
      exercise.

PMID- 24931067
TI  - Pulmonary artery stenosis and aneurysm with idiopathic mediastinal fibrosis.

PMID- 24931068
TI  - Effects of deep hypothermic circulatory arrest on the blood brain barrier in a
      cardiopulmonary bypass model--a pilot study.
AB  - BACKGROUND: Neurologic injury is common after cardiac surgery and disruption of
      the blood brain barrier (BBB) has been proposed as a contributing factor. We
      sought to study BBB characteristics in a rodent model of cardiopulmonary bypass
      (CPB) and deep hypothermic circulatory arrest (DHCA). METHODS: Adult rats were
      subjected to CPB/DHCA or to sham surgery. Analysis included Western blotting of
      relevant BBB proteins in addition to in vivo brain magnetic resonance imaging
      (MRI) with a clinically used low-molecular contrast agent. RESULTS: While
      quantitative analysis of BBB proteins revealed similar expression levels, MRI
      showed evidence of BBB disruption after CPB/DHCA compared to sham surgery.
      CONCLUSIONS: Combining molecular BBB analysis and MRI technology in a rodent
      model is a highly translatable approach to study adverse neurologic outcomes
      following CPB/DHCA.

PMID- 24931070
TI  - Prevalence of lower urinary tract symptoms, overactive bladder and urinary
      incontinence in western Turkey: results of a population-based survey.
AB  - OBJECTIVE: To estimate the prevalence of lower urinary tract symptoms, urinary
      incontinence and overactive bladder in western Turkey. METHOD: This cross
      sectional, population-based survey was carried out between May and October 2012.
      A random sample of 2128 women and men aged >=18 years was selected from the
      health registries. A questionnaire including sociodemographic data, comorbid
      conditions, lower urinary tract symptoms, overactive bladder and urinary
      incontinence symptoms, body mass index, vital signs, and dipstick urinalysis was
      developed. The questions were answered by the participants, and remaining data
      were provided by the site staff. International Continence Society definitions
      were used. RESULTS: A total of 1571 (74%) individuals agreed to participate, and
      analysis were carried out on 1555 people (636 men [40.9%] and 919 women [59.1%])
      after 16 individuals with a nitrite-positive dipstick test were excluded. Lower
      urinary tract symptoms were reported by 71.0% of the study population. The
      prevalence of storage, voiding and post-micturition symptoms were 56.1% (44.2%
      men, 64.1% women), 39.3% (40.9% men, 37.8% women) and 30.7% (38.6% men, 28.7%
      women), respectively. The most prevalent storage symptom was urgency, which was
      reported by 29.3% of the study population (20.1% men, 35.6% women). The
      prevalence of urge, stress and mixed urinary incontinence were: 6.5% (3.9% men,
      8.2% women), 14.1% (3.9% men, 21.2% women) and 5.6% (0.8% men, 9.0% women),
      respectively. CONCLUSION: The present study is the first and largest population
      based survey evaluating the prevalence of lower urinary tract symptoms, urinary
      incontinence and overactive bladder in Turkey. Our findings show these symptoms
      are highly prevalent in western Turkey.

PMID- 24931069
TI  - Painful macules of hand cholesterol crystal embolization successfully treated
      with oral corticosteroid, statin, and sarpogrelate.

PMID- 24931071
TI  - Unmet need for contraception: issues and challenges.
AB  - Unmet need for contraception has been a central indicator for monitoring the
      progress of family planning programs for 25 years. The purpose of this article is
      to provide a broad context for the more focused contributions that follow in this
      special issue. The validity and measurement of the concept of unmet need are
      discussed. We then present regional trends among married women since 1970. Major
      reductions in unmet need have been achieved, with the clear exception of sub
      Saharan Africa. Less success can be claimed in addressing the needs of sexually
      active unmarried women, who contribute nearly 20 percent to overall unmet need in
      developing countries. Prominent reasons for unmet need in settings where
      contraceptive uptake is low include social resistance and insufficient
      information concerning methods. As contraceptive use increases, the importance of
      these reasons wanes, but concerns regarding side effects and health impact remain
      a barrier, and discontinued users now constitute a large proportion of those with
      unmet need. Drawing on these reasons, we outline measures to further reduce unmet
      need. 

PMID- 24931072
TI  - Understanding unmet need: history, theory, and measurement.
AB  - During the past two decades, estimates of unmet need have become an influential
      measure for assessing population policies and programs. This article recounts the
      evolution of the concept of unmet need, describes how demographic survey data
      have been used to generate estimates of its prevalence, and tests the sensitivity
      of these estimates to various assumptions in the unmet need algorithm. The
      algorithm uses a complex set of assumptions to identify women: who are sexually
      active, who are infecund, whose most recent pregnancy was unwanted, who wish to
      postpone their next birth, and who are postpartum amenorrheic. The sensitivity
      tests suggest that defensible alternative criteria for identifying four out of
      five of these subgroups of women would increase the estimated prevalence of unmet
      need. The exception is identification of married women who are sexually active;
      more accurate measurement of this subgroup would reduce the estimated prevalence
      of unmet need in most settings. 

PMID- 24931073
TI  - Reasons for contraceptive nonuse among women having unmet need for contraception
      in developing countries.
AB  - The level of unmet need for contraception-an important motivator of international
      family planning programs and policies-has declined only slightly in recent
      decades. This study draws upon data from 51 surveys conducted between 2006 and
      2013 in Africa, Asia, and Latin America and the Caribbean to provide an updated
      review of the reasons why many married women having unmet need are not practicing
      contraception. We examine the reasons for contraceptive nonuse and how these
      reasons vary across countries and according to national levels of unmet need and
      contraceptive use. We present specific findings regarding the most widespread
      reasons for nonuse, particularly infrequent sex and concerns regarding side
      effects or health risks. Our findings suggest that access to services that
      provide a range of methods from which to choose, and information and counseling
      to help women select and effectively use an appropriate method, can be critical
      in helping women having unmet need overcome obstacles to contraceptive use. 

PMID- 24931074
TI  - Do natural methods count? underreporting of natural contraception in urban
      Burkina Faso.
AB  - Natural methods of contraception were widely used in developed countries until
      the late 1960s to space and limit childbirth. In France, when the first
      contraceptive surveys were conducted, researchers noticed that the use of natural
      methods was underreported, and questions to correct for this bias were
      subsequently added. The Demographic and Health Surveys do not currently include
      questions specific to natural methods. We added such questions to the standard
      DHS question regarding current contraceptive use when we conducted the Health and
      Demographic Surveillance System of Ouagadougou (2010 Ouaga HDSS) health survey in
      Burkina Faso among 758 women aged 15-49. Doing so enabled us to find a notable
      increase in the proportion of women in union who reported practicing
      contraception: 58 percent, compared with 38 percent in Ouagadougou in the 2010
      Burkina Faso DHS. Thirty-two percent of women reported using modern medical
      methods or condoms in both surveys, but use of natural methods was much greater
      in the 2010 Ouaga HDSS health survey (26 percent) than in the 2010 Burkina Faso
      DHS (5 percent). Many women classified as having unmet need for family planning
      in Ouagadougou by the DHS data are in fact users of natural methods. Additional
      questions that would measure use of natural methods more completely should be
      tested in different settings. 

PMID- 24931075
TI  - Demand for contraception to delay first pregnancy among young married women in
      India.
AB  - In India, evidence is sparse regarding the demand for contraception to delay
      first pregnancy among married young people. Using data drawn from a study
      conducted in six Indian states among 9,572 women aged 15-24 who were married for
      five or fewer years, we explore the scope of this demand, the extent to which it
      has been satisfied, and, using logistic regression analyses, the factors
      correlated with contraceptive use to delay first pregnancy among those reporting
      demand. Findings confirm considerable demand for contraception to postpone first
      pregnancy (51 percent). Of those with demand, only 10 percent had practiced
      contraception. Contraception was more likely to have been practiced by educated
      women, those aware of family planning methods before they were married, those
      exposed to quality sexuality education, and those who participated in marriage
      related decision making. Women who reported feeling pressure to prove their
      fertility were less likely to have practiced contraception.

PMID- 24931076
TI  - Unmet need for family planning in Ghana: the shifting contributions of lack of
      access and attitudinal resistance.
AB  - In Ghana, despite a 38 percent decline in the total fertility rate from 1988 to
      2008, unmet need for family planning among married women exposed to pregnancy
      risk declined only modestly in this period: from 50 percent to 42 percent.
      Examining data from the five DHS surveys conducted in Ghana during these years,
      we find that the relative contribution to unmet need of lack of access to
      contraceptive methods has diminished, whereas attitudinal resistance has grown.
      In 2008, 45 percent of women with unmet need experienced no apparent obstacles
      associated with access or attitude, 32 percent had access but an unfavorable
      attitude, and 23 percent had no access. Concerns regarding health as a reason for
      nonuse have been reported in greater numbers over these years and are now the
      dominant reason, followed by infrequent sex. An enduring resistance to hormonal
      methods, much of it based on prior experience of side effects, may lead many
      Ghanaian women, particularly the educated in urban areas, to use periodic
      abstinence or reduced coital frequency as an alternative to modern contraception.

PMID- 24931077
TI  - Unmet need and fertility decline: a comparative perspective on prospects in sub
      Saharan Africa.
AB  - This study assesses how changes in unmet need for family planning have
      contributed to contemporary fertility declines, and the implications of this
      historical record for further fertility decline, especially in sub-Saharan
      Africa. We examine joint trends at the national level in fertility, unintended
      fertility, and unmet need. We bring unintended fertility into the analysis
      because the underlying rationale for reducing unmet need is to avert unintended
      pregnancies and births. The association over time between unmet need and
      fertility is investigated using survey data from 45 countries in Africa, Asia,
      and Latin America and the Caribbean from the mid-1970s to the present. The
      empirical analysis finds that reduction in unmet need, especially unmet need for
      limiting, is strongly associated with fertility decline in Latin America and the
      Caribbean and in Asia and North Africa. Fertility decline in sub-Saharan Africa
      is weakly associated with trends in unmet need (and satisfaction of demand). We
      propose that the stark regional difference is due to measurement problems and to
      the fundamentally different character of fertility decline in sub-Saharan Africa,
      itself reflective of basic differences in pretransition reproductive regimes. 

PMID- 24931078
TI  - The impact of family planning programs on unmet need and demand for
      contraception.
AB  - Much of the existing literature on the demographic impact of family planning
      programs focuses on their role in increasing contraceptive use, which, in turn,
      accelerates fertility decline. What is not clear, however, is whether this effect
      operates solely through a reduction in unmet need brought about by eliminating
      obstacles to use or whether and to what extent the programs also affect demand
      for contraception through messages concerning the benefits of family planning.
      This article aims to shed additional light on this issue by analyzing data drawn
      from recent Demographic and Health Surveys conducted in 63 developing countries.
      The first section reviews general levels and trends in unmet need, demand, and
      use over the course of the fertility transition. The second section presents
      different types of evidence of program effects, including results from a
      controlled experiment and from country case studies. The evidence indicates a
      program impact on both unmet need and demand. 

PMID- 24931079
TI  - Using measurements of unmet need to inform program investments for health service
      integration.
AB  - Demographic and Health Survey (DHS) data could potentially inform optimal
      strategies to reach women having unmet need with contraceptive services through
      integrated service delivery. Using 2010-11 DHS data from Nepal, Senegal, and
      Uganda, we estimate the proportion of married or cohabitating women of
      reproductive age (MWRA) having unmet need for family planning (FP) who have
      accessed selected health services and therefore could be offered FP services
      through integrated service delivery. We find substantial missed opportunities to
      reach MWRA having unmet need for family planning (FP) in the three countries
      examined. We also find considerable variation within and between countries in the
      potential for integrated services to reach women having unmet need. Between 4
      percent and 57 percent of MWRA having unmet need in these countries could be
      reached through integration of FP into any single-service delivery platform we
      explored. This analysis has the potential to provide program managers with an
      evidence-based road map indicating which service-delivery platforms offer the
      greatest potential to reach the largest number of women having unmet need for
      contraception. 

PMID- 24931080
TI  - Reducing unmet need and unwanted childbearing: evidence from a panel survey in
      Pakistan.
AB  - Pakistan's high unmet need for contraception and low contraceptive prevalence
      remain a challenge, especially in light of the country's expected contribution to
      the FP2020 goal of expanding family planning services to an additional 120
      million women with unmet need. Analysis of panel data from 14 Pakistani districts
      suggests that efforts to reduce unmet need should also focus on empowering women
      who are currently practicing contraception to achieve their own reproductive
      intentions through continuation of contraceptive use of any method. Providing
      women with better quality of care and encouraging method switching would bridge
      the gap that exists when women are between methods and thus would reduce unwanted
      births. This finding is generalizable to other countries that, like Pakistan, are
      highly dependent on short-acting modern and traditional methods. The approach of
      preventing attrition among current contraceptive users would be at least as
      effective as persuading nonusers to adopt a method for the first time. 

PMID- 24931081
TI  - What Happened When CrossCheck Was Not Used for a Month in Journal of
      Neurogastroenterology and Motility?

PMID- 24931082
TI  - Is this the era of interstitial cells of cajal transplantation?

PMID- 24931084
TI  - Introduction: Magnetic resonance imaging comes of age in radiation oncology.

PMID- 24931085
TI  - The value of magnetic resonance imaging for radiotherapy planning.
AB  - The success of highly conformal radiotherapy techniques in the sparing of normal
      tissues or in dose escalation, or both, relies heavily on excellent imaging.
      Because of its superior soft tissue contrast, magnetic resonance imaging is
      increasingly being used in radiotherapy treatment planning. This review discusses
      the current clinical evidence to support the pivotal role of magnetic resonance
      imaging in radiation oncology. 

PMID- 24931086
TI  - Magnetic resonance imaging acquisition techniques for radiotherapy planning.
AB  - Magnetic resonance imaging (MRI) has a number of benefits for the planning of
      radiotherapy (RT), but its uptake into clinical practice has often been
      restricted to specialist research sites. There is often a lack of detailed MRI
      knowledge within the RT community and an apprehension of geometric distortions,
      both of which prevent its best utilization and merit the introduction of a
      standardized approach and common guidelines. This review sets out to address some
      of the issues involved in acquiring MRI scans for RT planning in the context of a
      number of clinical sites of interest and concludes with recommendations for its
      best practice in terms of imaging protocol and quality assurance. The article is
      of particular interest to the growing number of cancer therapy centers that are
      embarking on MRI simulation on either existing systems or their own dedicated
      scanners. 

PMID- 24931083
TI  - Insulin treatment normalizes retinal neuroinflammation but not markers of synapse
      loss in diabetic rats.
AB  - Diabetic retinopathy is one of the leading causes of blindness in developed
      countries, and a majority of patients with type I and type II diabetes will
      develop some degree of vision loss despite blood glucose control regimens. The
      effects of different insulin therapy regimens on early metabolic, inflammatory
      and neuronal retinal disease processes such as retinal neuroinflammation and
      synapse loss have not been extensively investigated. This study compared 3 months
      non-diabetic and streptozotocin (STZ)-induced diabetic Sprague Dawley rats.
      Diabetic rats received either no insulin treatment, systemic insulin treatment
      beginning after 1 week uncontrolled diabetes (early intervention, 11 weeks on
      insulin), or after 1.5 months uncontrolled diabetes (late intervention, 6 weeks
      on insulin). Changes in both whole animal metabolic and retinal inflammatory
      markers were prevented by early initiation of insulin treatment. These metabolic
      and inflammatory changes were also normalized by the later insulin intervention.
      Insulin treatment begun 1 week after diabetes induction ameliorated loss of
      retinal synapse markers. Synapse markers and presumably synapse numbers were
      equivalent in uncontrolled diabetes and when insulin treatment began at 1.5
      months of diabetes. These findings are in agreement with previous demonstrations
      that retinal synapses are lost within 1 month of uncontrolled diabetes and
      suggest that synapses are not regained with glycemic control and restoration of
      insulin signaling. However, increased expression of metabolic and inflammatory
      markers associated with diabetes was reversed in both groups of insulin
      treatment. This study also emphasizes the need for insulin treatment groups in
      diabetic retinopathy studies to provide a more faithful modeling of the human
      condition. 

PMID- 24931087
TI  - Point: Principles of magnetic resonance imaging integration in a computed
      tomography-based radiotherapy workflow.
AB  - Computed tomography (CT) is the primary imaging modality on which radiation
      therapy has been based, leading to a CT-based workflow that is well established.
      CT provides a geometrically accurate patient model on which accurate radiation
      planning occurs, and it is the basis of the present state-of-the-art image
      guidance systems, which are well integrated with the treatment unit. Magnetic
      resonance imaging (MRI) is becoming an increasingly important tool in radiation
      oncology, as it can provide anatomical and functional information regarding the
      tumor and normal tissues, which may be complimentary to information from CT
      alone. MRI may be integrated into a CT-based radiotherapy (RT) workflow, using
      image registration tools. Such tools are already an inherent part of the RT
      workflow, for multimodality and multiphasic image registration for radiation
      planning (for MRI, positron emission tomography, and other imaging) and for image
      guidance at the treatment unit. The rationale for MRI integration in a CT-based
      RT workflow is reviewed here, and technical challenges and solutions regarding
      image registration of MRI throughout the entire RT process are discussed. 

PMID- 24931088
TI  - Counterpoint: Opportunities and challenges of a magnetic resonance imaging-only
      radiotherapy work flow.
AB  - Magnetic resonance (MR) imaging plays an important role in modern radiotherapy.
      The benefits of MR as compared with those of computed tomography for the
      definition of target volumes is evident for many soft tissue tumor types. It has
      been suggested that for these patient groups, the computed tomography examination
      is unnecessary as part of the preparation for radiotherapy. Here, we review the
      rationale for an MR-only radiotherapy work flow, as well as the technical
      challenges and solutions connected to it. 

PMID- 24931090
TI  - Introduction: Systems for magnetic resonance image guided radiation therapy.

PMID- 24931089
TI  - Magnetic resonance image guided brachytherapy.
AB  - The application of magnetic resonance image (MRI)-guided brachytherapy has
      demonstrated significant growth during the past 2 decades. Clinical improvements
      in cervix cancer outcomes have been linked to the application of repeated MRI for
      identification of residual tumor volumes during radiotherapy. This has changed
      clinical practice in the direction of individualized dose administration, and
      resulted in mounting evidence of improved clinical outcome regarding local
      control, overall survival as well as morbidity. MRI-guided prostate high-dose
      rate and low-dose-rate brachytherapies have improved the accuracy of target and
      organs-at-risk delineation, and the potential exists for improved dose
      prescription and reporting for the prostate gland and organs at risk.
      Furthermore, MRI-guided prostate brachytherapy has significant potential to
      identify prostate subvolumes and dominant lesions to allow for dose
      administration reflecting the differential risk of recurrence. MRI-guided
      brachytherapy involves advanced imaging, target concepts, and dose planning. The
      key issue for safe dissemination and implementation of high-quality MRI-guided
      brachytherapy is establishment of qualified multidisciplinary teams and
      strategies for training and education. 

PMID- 24931091
TI  - A facility for magnetic resonance-guided radiation therapy.
AB  - Magnetic resonance (MR) imaging is routinely employed in the design of
      radiotherapy (RT) treatment plans for many disease sites. It is evident that
      tighter integration of MR imaging into the RT process would increase confidence
      in dose placement and facilitate the integration of new MR imaging information
      (including anatomical and functional imaging) into the therapy process. To this
      end, a dedicated MR-guided RT (MRgRT) facility has been created that integrates a
      state-of-the-art linear accelerator delivery system, high-dose rate brachytherapy
      afterloader, and superconducting MR scanner to allow MR-based online treatment
      guidance, adaptive replanning, and response monitoring while maintaining the
      clinical functionality of the existing delivery systems. This system is housed
      within a dedicated MRgRT suite and operates in a coordinated fashion to assure
      safe and efficient MRgRT treatments. 

PMID- 24931093
TI  - The rotating biplanar linac-magnetic resonance imaging system.
AB  - We have successfully built linac-magnetic resonance imaging (MR) systems based on
      a linac waveguide placed between open MR planes (perpendicular) or through the
      central opening of one of the planes (parallel) to improve dosimetric properties.
      It rotates on a gantry to irradiate at any angle. Irradiation during MR imaging
      and automatic 2-dimensional MR image-based target tracking and automatic beam
      steering to the moving target have been demonstrated with our systems. The
      functioning whole-body system (0.6-T MR and 6-MV linac) has been installed in an
      existing clinical vault without removing the walls or the ceiling and without the
      need of a helium exhaust vent. 

PMID- 24931092
TI  - The ViewRay system: magnetic resonance-guided and controlled radiotherapy.
AB  - A description of the first commercially available magnetic resonance imaging
      (MRI)-guided radiation therapy (RT) system is provided. The system consists of a
      split 0.35-T MR scanner straddling 3 (60)Co heads mounted on a ring gantry, each
      head equipped with independent doubly focused multileaf collimators. The MR and
      RT systems share a common isocenter, enabling simultaneous and continuous MRI
      during RT delivery. An on-couch adaptive RT treatment-planning system and
      integrated MRI-guided RT control system allow for rapid adaptive planning and
      beam delivery control based on the visualization of soft tissues. Treatment of
      patients with this system commenced at Washington University in January 2014. 

PMID- 24931094
TI  - The Australian magnetic resonance imaging-linac program.
AB  - The Australian magnetic resonance imaging (MRI)-Linac program is a $16-million
      government-funded project to advance the science and clinical practice of
      exquisite real-time anatomical and physiological adaptive cancer therapy. The
      centerpiece of the program is a specifically designed 1-T open-bore MRI/6-MV
      linac system that is planned for delivery and completion of installation in 2014.
      Current scientific endeavors include engineering discovery in MRI component
      design, quantifying MRI and linac interactions, and developing image guidance and
      adaptation strategies. 

PMID- 24931095
TI  - The magnetic resonance imaging-linac system.
AB  - The current image-guided radiotherapy systems are suboptimal in the esophagus,
      pancreas, kidney, rectum, lymph node, etc. These locations in the body are not
      easily accessible for fiducials and cannot be visualized sufficiently on cone
      beam computed tomographies, making daily patient set-up prone to geometrical
      uncertainties and hinder dose optimization. Additional interfraction and
      intrafraction uncertainties for those locations arise from motion with breathing
      and organ filling. To allow real-time imaging of all patient tumor locations at
      the actual treatment position a fully integrated 1.5-T, diagnostic quality,
      magnetic resonance imaging with a 6-MV linear accelerator is presented. This
      system must enable detailed dose painting at all body locations. 

PMID- 24931096
TI  - Magnetic resonance imaging of the tumor microenvironment in radiotherapy:
      perfusion, hypoxia, and metabolism.
AB  - The tumor microenvironment is characterized by hypoxia, low pH, and high
      interstitial fluid pressure. Hypoxic regions in tumors with low partial pressure
      of oxygen (pO2) levels can result in resistance to radiotherapy, thus causing
      local failure. Therefore, it would be desirable to noninvasively measure pO2
      levels in the tumor before, during, and after treatment to better customize
      therapy and follow treatment response. Several techniques used in preclinical and
      clinical studies to obtain the pO2 status of tissue, such as dynamic contrast
      enhanced magnetic resonance imaging, blood oxygen level-dependent imaging, and
      electron paramagnetic resonance imaging, are reviewed. Furthermore, the ability
      to hyperpolarize specific metabolic substrates that are isotopically labeled with
      (13)C coupled with magnetic resonance spectroscopy enables noninvasive imaging of
      tissue metabolism, such as glycolysis. 

PMID- 24931098
TI  - Magnetic resonance-guided adaptive radiotherapy: a solution to the future.
AB  - Magnetic resonance imaging-guided adaptive radiotherapy would make available the
      best in anatomical and functional imaging during the course of radiation therapy.
      The possible methodology of magnetic resonance imaging-guided adapted
      radiotherapy and possible clinical applications are discussed. 

PMID- 24931099
TI  - Crystal structure tuning in GaAs nanowires using HCl.
AB  - The use of HCl during growth of nanowires presents new possibilities for
      controlling the growth dynamics and resulting nanowire properties. In this paper,
      we investigate the effects of in situ HCl on the growth of Au-seeded GaAs
      nanowires in a growth regime where both wurtzite and zinc blende crystal
      structures are possible to achieve. We find that HCl changes the crystal
      structure of the nanowires from pure wurtzite to defect-free zinc blende. By
      comparing the growth of wurtzite-zinc blende heterostructures with and without
      the addition of HCl, it is deduced that HCl mainly interacts with Ga species
      prior incorporation, reducing the amount of Ga available to contribute to the
      growth. We conclude that the change in crystal structure is related to the
      reduction of Ga adatoms, and demonstrate the realization of wurtzite-zinc blende
      heterostructures with atomically sharp interfaces achieved only by adding HCl. 

PMID- 24931097
TI  - Clinical applications for diffusion magnetic resonance imaging in radiotherapy.
AB  - In this article, we review the clinical applications of diffusion magnetic
      resonance imaging (MRI) in the radiotherapy treatment of several key clinical
      sites, including those of the central nervous system, the head and neck, the
      prostate, and the cervix. Diffusion-weighted MRI (DWI) is an imaging technique
      that is rapidly gaining widespread acceptance owing to its ease and wide
      availability. DWI measures the mobility of water within tissue at the cellular
      level without the need of any exogenous contrast agent. For radiotherapy
      treatment planning, DWI improves upon conventional imaging techniques, by better
      characterization of tumor tissue properties required for tumor grading,
      diagnosis, and target volume delineation. Because DWI is also a sensitive marker
      for alterations in tumor cellularity, it has potential clinical applications in
      the early assessment of treatment response following radiation therapy. 

PMID- 24931100
TI  - miR-146a and miR-155 expression in PBMCs from patients with Sjogren's syndrome.
AB  - BACKGROUND: An increasing number of studies have revealed that microRNA (miRNA)
      contributes to the pathogenesis of autoimmune diseases. The objective of this
      study is to investigate the miR-146a and miR-155 levels in peripheral mononuclear
      blood cells from patients with primary Sjogren's syndrome (pSS) who were not
      receiving medications and to examine the correlations between these miRNA levels
      and the clinical features of the disease. METHOD: Using real-time polymerase
      chain reaction analysis of miRNAs, the miR-146a and miR-155 expression levels
      were assessed in peripheral mononuclear blood cells from 27 patients with pSS and
      22 healthy controls, and the relationships between these miRNA levels and the
      visual analog scale (VAS) scores for dry mouth, dry eyes, and parotid gland
      swelling were investigated. RESULTS: Compared with the healthy controls, the miR
      146a expression level was significantly increased in the patients with pSS (P =
      0.0182) and was positively correlated with the VAS scores for parotid swelling (r
      = 0.4475, P = 0.0192) and dry eyes (r = 0.4051, P = 0.0361). Although the miR-155
      expression level was significantly decreased in the patients with pSS (P =
      0.0131), the miR-155 expression positively correlated with the VAS score for dry
      eyes (r = 0.4894, P = 0.0096). CONCLUSION: Our results demonstrated miR-146a
      overexpression and miR-155 underexpression in the peripheral mononuclear blood
      cells of the patients with pSS. Furthermore, the expression levels of these
      miRNAs correlated with the patients' clinical features. Our data suggest that miR
      146a and miR-155 might play important roles in the pathogenesis of pSS and that
      their expression levels may be useful for diagnosing pSS and for predicting
      disease activity and therapeutic responses.

PMID- 24931102
TI  - Genetics of lipid traits: Genome-wide approaches yield new biology and clues to
      causality in coronary artery disease.
AB  - A wealth of novel lipid loci have been identified through a variety of approaches
      focused on common and low-frequency variation and collaborative metaanalyses in
      multiethnic populations. Despite progress in identification of loci, the task of
      determining causal variants remains challenging. This work will undoubtedly be
      enhanced by improved understanding of regulatory DNA at a genomewide level as
      well as new methodologies for interrogating the relationships between noncoding
      SNPs and regulatory regions. Equally challenging is the identification of causal
      genes at novel loci. Some progress has been made for a handful of genes and
      comprehensive testing of candidate genes using multiple model systems is
      underway. Additional insights will be gleaned from focusing on low frequency and
      rare coding variation at candidate loci in large populations. This article is
      part of a Special Issue entitled: From Genome to Function.

PMID- 24931101
TI  - Cigarette smoke alters IL-33 expression and release in airway epithelial cells.
AB  - Airway epithelium is a regulator of innate immune responses to a variety of
      insults including cigarette smoke. Cigarette smoke alters the expression and the
      activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an
      alarmin, increases innate immunity Th2 responses. The aims of this study were to
      explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have
      altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter
      both intracellular expression (mRNA and protein) and release of IL-33 in
      bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also
      explored. Mini-BALs, but not sera, from smokers show reduced concentrations of IL
      33. The expression of IL-33 was increased also in bronchial epithelium from
      smokers. 20% CSE reduced IL-33 release but increased the mRNA for IL-33 by real
      time PCR and the intracellular expression of IL-33 in bronchial epithelial cells
      as confirmed by flow cytometry, immunocytochemistry and western blot analysis.
      The effect of CSE on IL-33 expression was also observed in primary bronchial
      epithelial cells. IL-33 expression was mainly concentrated within the cytoplasm
      of the cells. LPS, an agonist of TLR4, reduced IL-33 expression, and an inhibitor
      of TLR4 increased the intracellular expression of IL-33. In conclusion, the
      release of IL-33 is tightly controlled and, in smokers, an altered activation of
      TLR4 may lead to an increased intracellular expression of IL-33 with a limited IL
      33 release. 

PMID- 24931104
TI  - Determination of 135Cs and 135Cs/137Cs atomic ratio in environmental samples by
      combining ammonium molybdophosphate (AMP)-selective Cs adsorption and ion
      exchange chromatographic separation to triple-quadrupole inductively coupled
      plasma-mass spectrometry.
AB  - Since the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011, the
      activity ratio of (134)Cs/(137)Cs has been widely used as a tracer for
      contamination source identification. However, because of the short half-life of
      (134)Cs (2.06 y), this tracer will become unavailable in the near future. This
      article presents an analytical method for the determination of the long-lived
      (135)Cs (t(2/1) = 2 * 10(6) y) and the atomic ratio of (135)Cs/(137)Cs, as a
      promising geochemical tracer, in environmental samples. The analytical method
      involves ammonium molybdophosphate (AMP)-selective adsorption of Cs and
      subsequent two-stage ion-exchange chromatographic separation, followed by
      detection of isolated radiocesium isotopes via triple-quadrupole inductively
      coupled plasma-mass spectrometry (ICP-MS/MS). The AMP-selective adsorption of Cs
      and the chromatographic separation system showed high decontamination factors
      (10(4)-10(5)) for interfering elements, such as Ba, Mo, Sb, and Sn. Using ICP
      MS/MS, only selected ions enter the collision/reaction cell to react with N2O,
      reducing the isobaric interferences ((135)Ba(+) and (137)Ba(+)) and polyatomic
      interferences ((95) Mo(40)Ar(+), (97) Mo(40)Ar(+), (119)Sn(16)O(+), and
      (121)Sb(16)O(+)) produced by sample matrix ions. The high abundance sensitivity
      (10(-9) for the (135)Cs/(133)Cs ratio) provided by ICP-MS/MS allowed reliable
      analysis of (135)Cs and (137)Cs isotopes with the lowest detection limits ever
      reported by mass counting methods (0.01 pg mL(-1) and 0.006 pg mL(-1),
      respectively). The developed analytical method was successfully applied to the
      determination of (135)Cs and (137)Cs isotopes in environmental samples (soil,
      litter, and lichen) collected after the FDNPP accident for contamination source
      identification.

PMID- 24931103
TI  - [Prevalence of attention deficit/hyperactivity disorder symptoms in outpatient
      adolescents and young adults with other psychiatric disorders refractory to
      previous treatments].
AB  - INTRODUCTION: The aim of the current study was to assess the prevalence of
      symptoms of attention deficit/hyperactivity disorder (ADHD) in adolescents and
      young adults diagnosed with other primary psychiatric disorders, who had not
      responded to previous treatments. MATERIAL AND METHODS: A total of 795
      outpatients aged 15 to 24 years were included. The presence of ADHD was studied
      using DSM-IV criteria and the frequency of symptoms using the 18 item DuPaul ADHD
      Rating Scale. RESULTS: ADHD (DSM-IV criteria) was present in 48 patients (6%),
      none of whom had previously received the diagnosis. A total of 260 patients
      (32.7%) met the criteria for moderate ADHD and between them, severity of primary
      psychiatric disorder was higher according to the CGI-S (P=.007). Risk factors for
      moderate ADHD symptoms were the presence of substance use disorders (SUD) (odds
      ratio=1.543, P=.01) and borderline personality disorders (odds ratio =2.173,
      p=.0001). CONCLUSION: Unrecognized ADHD was present in 6% of patients; moreover
      32.7% of the sample also presented moderate symptoms of the disorder. Screening
      for ADHD in young patients with refractory response to primary disorder
      treatment, mainly those with substance use disorders, conduct and personality
      disorders is highly advisable, due to the high frequency of ADHD comorbidity in
      these psychiatric disorders.

PMID- 24931106
TI  - Assessment of 120 maxillofacial aneurysmal bone cysts: a nationwide quest to
      understand this enigma.
AB  - PURPOSE: Compared with other maxillofacial lesions, oral and maxillofacial (OM)
      aneurysmal bone cysts (ABCs) are rare, and most studies have been case reports.
      Because the features or radiographic findings of 1 case could not be
      representative of the whole, conclusions cannot be drawn and data analyses will
      not be feasible. Our aim was to assess and describe the clinical and
      histopathologic characteristics of a large sample of subjects with ABCs. To our
      knowledge, the present case series of OM ABCs is the largest ever reported.
      MATERIALS AND METHODS: To address our research purpose, we designed and
      implemented a retrospective case series. A multicenter retrospective cohort study
      of patient charts dated from 1967 to 2013 (46 years) at 10 major universities in
      8 cities was undertaken to assess OM ABCs nationwide. Subjects were included if
      they had documented chart data and definitive histopathologic slides confirming
      the diagnosis and treatment of ABC. They were excluded if their histopathologic
      slides did not confirm the diagnosis of an ABC. Data were collected, and special
      forms were completed. Variables such as age, gender, site (ie, maxilla, mandible,
      anterior, posterior), histologic type (ie, solid, mixed, vascular), signs,
      symptoms, radiographic features (ie, radiolucency, unicystic or multilocular),
      and outcomes (ie, treatment modal, recurrence, complications) of the lesion were
      evaluated and documented by OM surgeons and confirmed by OM pathologists for
      assurance. Data analyses were performed using Statistical Package for Social
      Sciences, version 20, software (SPSS, Chicago, IL) (P < .05). RESULTS: We
      assessed the medical records and histopathologic slides of 120 patients diagnosed
      and treated for OM ABCs nationwide. Of these patients, 69 were male (57.5%) and
      51 were female (42.5%), with no predilection found. The key findings were as
      follows. The mean age of occurrence was 20.7 +/- 2.5 years (range 4 to 78), and
      occurrence was significantly greater in the first 2 decades of life (P < .001).
      The incidence was 2.6 cases/year. ABCs were significantly more common in the
      mandible (P < .05) and posterior areas (P < .05). The most common histopathologic
      type was the mixed type (P < .05). Firm swelling was the most common clinical
      presentation (P < .05); all cases were radiolucent and commonly unilateral (P <
      .05). Most were treated by excision and curettage. Recurrence was reported in 11
      patients (9.2%) during the follow-up period (1 to 45 years). CONCLUSIONS: The
      present retrospective cohort found ABCs with a variable presentation, disease
      course, and histopathologic type, with no gender predilection. ABCs were
      significantly more common in childhood and adolescence and in the mandible and
      posterior areas of the jaws. Of the cases reviewed, 90% were treated by excision
      and curettage. ABCs had a relatively low recurrence rate (<10%), precluding the
      need to perform aggressive surgery primarily.

PMID- 24931105
TI  - Low-dose recombinant human bone morphogenetic protein-2 to enhance the osteogenic
      potential of the Schneiderian membrane in the early healing phase: in vitro and
      in vivo studies.
AB  - PURPOSE: The objectives of this study were to confirm the osteogenic potential of
      the Schneiderian membrane and to elucidate the early healing pattern of low-dose
      recombinant human bone morphogenetic protein-2 (rhBMP-2)-coated biphasic calcium
      phosphate (BCP). MATERIALS AND METHODS: The osteogenic potential of the
      Schneiderian membrane and enhancement by rhBMP-2 were evaluated by in vitro
      analysis. RhBMP-2-coated BCP (experimental group) and BCP soaked with saline
      (control group) were applied to the maxillary sinus in rabbits. After 2 weeks,
      micro-computed tomographic and histometric analyses were performed. RESULTS:
      Enhanced osteogenic potential was found when cells from the Schneiderian membrane
      were treated with rhBMP-2. Micro-computed tomographic analysis showed that the
      total augmented volume was significantly larger in the experimental group.
      Different healing patterns were observed in 3 regions, although the area of new
      bone did not differ significantly. Although more newly formed bone appeared,
      particularly along the Schneiderian membrane in the experimental group, the
      difference was not statistically significant. CONCLUSIONS: RhBMP-2 enhanced the
      osteogenic potential of the Schneiderian membrane in vitro. However, low-dose
      rhBMP-2-coated BCP failed to exert a statistically significant effect in vivo,
      although it appeared to be effective in sinus augmentation specifically for the
      volumetric increase in the early phase.

PMID- 24931107
TI  - Functional reconstruction of the lower lip with Fujimori flap and long-term
      follow-up with clinical and electrophysiologic evaluations.
AB  - PURPOSE: The Fujimori gate flap is an innervated flap raised from the nasolabial
      area for reconstruction of the lower lip. No electromyographic or clinical long
      term studies have analyzed the long-term outcomes of lower lip reconstruction
      performed using this method. The aim of the present study was to assess the
      outcomes of lower lip reconstruction with the Fujimori gate flap using clinical
      and electrophysiologic examinations. PATIENTS AND METHODS: Ten patients who had
      been treated with this procedure were evaluated clinically and
      electrophysiologically. The follow-up period was 1 year for all patients, and the
      patients underwent regular assessments. RESULTS: All flaps survived completely,
      and no wound healing problems were encountered. Four patients underwent revision
      in the late postoperative period. The electrophysiologic studies revealed the
      presence of reinnervation in all 10 patients. CONCLUSIONS: In the present study,
      we found that the Fujimori gate flap is a versatile flap for ideal reconstruction
      of lower lip defects. Our electrophysiologic assessments showed that the
      transferred muscle had undergone reinnervation and that the donor area
      innervation had been preserved. The findings from the serial clinical and
      electrophysiologic assessments indicated satisfactory results.

PMID- 24931108
TI  - A patient with pemphigus foliaceus and myasthenia gravis treated by a cortisol
      secreting adrenal adenoma.

PMID- 24931109
TI  - Identification of the neural component of torque during manually-applied
      spasticity assessments in children with cerebral palsy.
AB  - Clinical assessment of spasticity is compromised by the difficulty to distinguish
      neural from non-neural components of increased joint torque. Quantifying the
      contributions of each of these components is crucial to optimize the selection of
      anti-spasticity treatments such as botulinum toxin (BTX). The aim of this study
      was to compare different biomechanical parameters that quantify the neural
      contribution to ankle joint torque measured during manually-applied passive
      stretches to the gastrocsoleus in children with spastic cerebral palsy (CP). The
      gastrocsoleus of 53 children with CP (10.9 +/- 3.7 y; females n = 14;
      bilateral/unilateral involvement n = 28/25; Gross Motor Functional Classification
      Score I-IV) and 10 age-matched typically developing (TD) children were assessed
      using a manually-applied, instrumented spasticity assessment. Joint angle
      characteristics, root mean square electromyography and joint torque were
      simultaneously recorded during passive stretches at increasing velocities. From
      the CP cohort, 10 muscles were re-assessed for between-session reliability and 19
      muscles were re-assessed 6 weeks post-BTX. A parameter related to mechanical
      work, containing both neural and non-neural components, was compared to newly
      developed parameters that were based on the modeling of passive stiffness and
      viscosity. The difference between modeled and measured response provided a
      quantification of the neural component. Both types of parameters were reliable
      (ICC > 0.95) and distinguished TD from spastic muscles (p < 0.001). However, only
      the newly developed parameters significantly decreased post-BTX (p = 0.012).
      Identifying the neural and non-neural contributions to increased joint torque
      allows for the development of individually tailored tone management.

PMID- 24931110
TI  - History of falls, balance performance, and quality of life in older cancer
      survivors.
AB  - Older cancer survivors may be predisposed to falls because of the sequalae
      associated with cancer and its treatments. This study examined the association
      between the fall history, balance performance, and health-related quality of life
      (QoL) in older, community-dwelling cancer survivors who had completed primary
      cancer treatments. Forty-one cancer survivors (age = 67.9 +/- 8.8 years)
      participated in the study. Balance performance was examined using the Activities
      specific Balance Confidence Scale (ABC) and the Balance Evaluation Systems Test
      (BESTest). Scores from the Physical Component Summary (PCS) and Mental Component
      Summary (MCS) of the SF-36v2 were obtained to assess the QoL. The demographics
      and health status were comparable between the fallers and non-fallers. While 54%
      of the participants had experienced at least one fall in the past 12 months, 30%
      had experienced two or more falls. Spearman's correlation analysis revealed a
      significant relationship between the outcomes from the ABC and the PCS (p <
      0.001), and between the BESTest and the PCS (p < 0.001). Only the PCS
      significantly differentiated fallers from non-fallers (p < 0.01). Logistic
      regression analysis estimated that a one-unit increase in the PCS score
      significantly reduced the odds of falling by 13% (p < 0.01). The results
      demonstrate that in older cancer survivors, falls are a significant problem and
      balance control is a determinant of perceived physical function and well-being.
      Older cancer survivors reporting a poor QoL in the physical health domain may
      have higher risks of falling. Future studies are needed to examine the risk
      factor profiles of falls and the interventions to prevent falls in older cancer
      survivors.

PMID- 24931111
TI  - A characteristic pattern in the postural sway of unilateral vestibular impaired
      patients.
AB  - The statistical properties of the center of pressure (COP) change over time, and 
      invariant methods of the COP analysis is not sufficient to monitor the changes.
      Therefore, dynamic temporal information of the COP signals has been important in
      assessing the postural stability. The purpose of this study was to evaluate the
      characteristic pattern of time-frequency dynamics during the upright stance in
      patients with unilateral vestibular dysfunction (UVD). This study included 20
      dizzy patients with UVD and age-matched 20 control subjects without any
      vestibular disorder. The COP signals were collected using a single standard force
      platform and a spectral analysis including the time-frequency dynamics was
      carried out on the basis of the maximum entropy method (MEM) by using a segment
      time series analysis. The power spectral density (PSD) analysis exhibited an
      exponential decreasing shape (1/f (-)(beta)) when plotted on a double logarithmic
      scale. The average value of beta in the low frequency range of less than 1 Hz in
      the UVD group was significantly lower than that in the control group (p < 0.05)
      in the medial-lateral (ML) direction under eyes closed condition. In the segment
      time series analysis, the peak frequency of the COP signals in the patients with
      UVD gradually converged to the frequency range of 0.1-0.2 Hz in the ML direction
      under EC condition. Our results suggest that the segment time series analysis of
      the COP signals can derive a characteristic pattern related to the UVD. It may
      indicate an increased reflexivity of the COP fluctuation by the UVD, resulting in
      inducing the instability.

PMID- 24931112
TI  - Dynamic instability during post-stroke hemiparetic walking.
AB  - Falls and fall-related injuries cause extremely costly and potentially fatal
      health problems in people post-stroke. However, there is no global indicator of
      walking instability for detecting which individuals will have increased risk of
      falls. The purposes of this study were to directly quantify walking stability in
      stroke survivors and neurologically intact controls and to determine which
      stability measures would reveal the changes in walking stability following
      stroke. This study thus provided an initial step to establish objective measures
      for identifying potential fallers. Nine post-stroke individuals and nine controls
      walked on a treadmill at four different speeds. We computed short-term local
      divergence exponent (LDE) and maximum Floquet multiplier (maxFM) of the trunk
      motion, average and variability of dynamic margins of stability (MOS) and step
      spatiotemporal measures. Post-stroke individuals demonstrated larger short-term
      LDE (p = 0.002) and maxFM (p = 0.041) in the mediolateral (ML) direction compared
      to the controls but remained orbitally stable (maxFM < 1). In addition, post
      stroke individuals walked with greater average step width (p = 0.003) but similar
      average ML MOS (p = 0.154) compared to the controls. Post-stroke individuals also
      exhibited greater variability in all MOS and step measures (all p < 0.005). Our
      findings indicate that post-stroke individuals walked with greater local and
      orbital instability and gait variability than neurologically intact controls. The
      results suggest that short-term LDE of ML trunk motion and the variability of MOS
      and step spatiotemporal measures detect the changes in walking stability
      associated with stroke. These stability measures may have the potential for
      identifying those post-stroke individuals at increased risk of falls.

PMID- 24931113
TI  - Extended high cut-off haemodialysis for myeloma cast nephropathy in Auckland,
      2008-2012.
AB  - Myeloma cast nephropathy contributes to high morbidity and early mortality
      associated with the development of end-stage renal disease. Treatment with
      extended high cut-off haemodialysis coupled with novel anti-myeloma therapies
      enables significant reduction of serum-free light chains and has been shown to
      improve renal outcomes. In this case series, medical records of 6 patients who
      received high cut-off haemodialysis for biopsy-proven cast nephropathy were
      retrospectively reviewed. Patients received a total of 344 hours of high cut-off
      haemodialysis and concurrent chemotherapy. Only 50% became dialysis independent
      following treatment. One patient who achieved sustained remission remained
      dialysis dependent. The added benefit of high cut-off haemodialysis in the light
      of novel anti-myeloma therapies requires further evaluation. 

PMID- 24931114
TI  - Effect of corticosteroid therapy on renal pathology in IgG4-related kidney
      disease accompanying glomerulonephritis.

PMID- 24931115
TI  - Simultaneous determination of citrulline and arginine in human blood plasma by
      capillary electrophoresis with ultraviolet absorption detection.
AB  - A new capillary electrophoresis method to measure human blood plasma arginine and
      citrulline levels in a single run without derivatization was established. After
      adding homoarginine as internal standard, plasma proteins were removed by a 90:10
      v/v acetonitrile/ammonia mixture. Arginine and citrulline were detected by an
      ultraviolet detector at 190 nm and separated in 11.65 and 20.43 min,
      respectively, by using a 75 mmol/L Tris phosphate solution at pH 1.2 as a
      background electrolyte. Limits of detection were 0.8 and 5 MUmol/L for arginine
      and citrulline, respectively. Precision tests indicated a good repeatability of
      migration times and of peak area both for citrulline (CV% = 0.82 and 3.19) and
      arginine (CV% = 0.65 and 2.79). The CV% for intra- and interassay tests were,
      respectively, 1.84 and 3.23 for citrulline and 1.25 and 1.50 for arginine. Mean
      recovery was 101.5 and 98.5% for citrulline and arginine, respectively. The
      performance of the developed method was assessed by measuring plasma arginine
      levels in 52 subjects and the data were compared with those obtained by our
      previous assay. The new method was then applied to assess plasma citrulline and
      arginine in ten chronic kidney disease patients under hypolipidemic therapy with
      statin. 

PMID- 24931116
TI  - An exploration of worry content and catastrophic thinking in middle-aged and
      older-aged adults with and without Parkinson's disease.
AB  - OBJECTIVE: Worry is a common and distressing problem in Parkinson's disease (PD).
      However, little is known about the nature and content of worry in PD and how it
      might differ to non-PD populations. The study aimed to explore the content and
      nature of worry in middle-aged and older-aged adults with and without PD. METHOD:
      Four groups of participants, 20 PD patients (10 high worry and 10 low worry) and
      19 middle-aged and older-aged adults (10 high worry and nine low worry),
      completed the catastrophising interview (CI) for three worry topics. Worriers
      were classified (high/low) on the basis of Penn State Worry Questionnaire scores.
      Data were analysed using framework analysis. RESULTS: High worriers showed a
      greater diversity of worry topics than low worriers. Health worries
      differentiated high and low worriers in the non-PD sample but were common across
      all PD participants. The CI revealed that the root concern of worry was often
      different to that initially described. In particular, PD high worriers were more
      likely to express underlying concerns about negative self-perception and
      death/severe incapacity. CONCLUSION: The CI was able to identify the root cause
      of worry, demonstrating the value of this technique in the exploration and
      treatment of worry and psychological distress. Exploring worry content may help
      to distinguish patients with problematic worry, with worries about self
      perception and death/severe incapacity characteristic of high worriers.
      Therapeutic interventions designed to alleviate problematic worry and distress in
      PD need to take account of the realities of living with PD and the potentially
      realistic nature of worries that may appear catastrophic in a healthy population.

PMID- 24931117
TI  - Enzymatic properties and substrate specificity of a bacterial phosphatidylcholine
      synthase.
AB  - Phosphatidylcholine (PC) is a rare membrane lipid in bacteria, but is crucial for
      virulence of the plant pathogen Agrobacterium tumefaciens and various other
      pathogens. Agrobacterium tumefaciens uses two independent PC biosynthesis
      pathways. One is dependent on the integral membrane protein PC synthase (Pcs),
      which catalyzes the conversion of cytidine diphosphate-diacylglycerol (CDP-DAG)
      and choline to PC, thereby releasing a cytidine monophosphate (CMP). Here, we
      show that Pcs consists of eight transmembrane segments with its N- and C-termini
      located in the cytoplasm. A cytoplasmic loop between the second and third
      membrane helix contains the majority of the conserved amino acids of a CDP
      alcohol phosphotransferase motif (DGX2 ARX12 GX3 DX3 D). Using point mutagenesis,
      we provide evidence for a crucial role of this motif in choline binding and
      enzyme activity. To study the catalytic features of the enzyme, we established a
      purification protocol for recombinant Pcs. The enzyme forms stable oligomers and
      exhibits broad substrate specificity towards choline derivatives. The presence of
      CDP-DAG and manganese is a prerequisite for cooperative binding of choline. PC
      formation by Pcs is reversible and proceeds via two successive reactions. In a
      first choline- and manganese-independent reaction, CDP-DAG is hydrolyzed
      releasing a CMP molecule. The resulting phosphatidyl intermediate reacts with
      choline in a second manganese-dependent step to form PC. STRUCTURED DIGITAL
      ABSTRACT: Pcs and Pcs bind by molecular sieving (1, 2, 3).

PMID- 24931119
TI  - Brief overview on cellulose dissolution/regeneration interactions and mechanisms.
AB  - The development of cellulose dissolution/regeneration strategies constitutes an
      increasingly active research field. These are fundamental aspects of many
      production processes and applications. A wide variety of suitable solvents for
      cellulose is already available. Nevertheless, most solvent systems have important
      limitations, and there is an intense activity in both industrial and academic
      research aiming to optimize existing solvents and develop new ones. Cellulose
      solvents are of highly different nature giving great challenges in the
      understanding of the subtle balance between the different interactions. Here, we
      briefly review the cellulose dissolution and regeneration mechanisms for some
      selected solvents. Insolubility is often attributed to strong intermolecular
      hydrogen bonding between cellulose molecules. However, recent work rather
      emphasizes the role of cellulose charge and the concomitant ion entropy effects,
      as well as hydrophobic interactions. 

PMID- 24931118
TI  - Characterization, tissue distribution and regulation of neuropeptideY in
      Schizothorax prenanti.
AB  - In this study, the full-length neuropeptide Y (npy) complementary (c)DNA was
      cloned in ya fish Schizothorax prenanti. npy cDNA was composed of 789 nucleotides
      with a 288 nucleotide open reading frame encoding a protein of 96 amino acids.
      The deduced amino acid sequences contained a 28 amino acids signal peptide
      followed by a 36 amino acids mature neuropeptide Y (NPY). The npy mRNA was
      expressed mainly in the brain and eye as detected by real-time quantitative
      polymerase chain reaction RT-PCR (rt-qPCR). The S. prenanti NPY was detectable
      from blastulation to hatch, suggesting that npy might be involved in the late
      embryonic development of S. prenanti. An experiment was conducted to determine
      the expression profile of npy during feeding of a single meal and during long
      term fasting. The expression level of npy in fed fish was significantly decreased
      at 0.5, 1.5, 3 and 9 h post-feeding (hpf) than in fasting fish. Fasting for 14
      days induced an increase in npy messenger (m)RNA expression in the brain.
      Overall, the results suggest that NPY is a conserved peptide that might be
      involved in the regulation of feeding and other physiological function in S.
      prenanti.

PMID- 24931120
TI  - Size-matched alkyne-conjugated cyanine fluorophores to identify differences in
      protein glycosylation.
AB  - Currently, there are few methods to detect differences in posttranslational
      modifications (PTMs) in a specific manner from complex mixtures. Thus, we
      developed an approach that combines the sensitivity and specificity of click
      chemistry with the resolution capabilities of 2D-DIGE. In "Click-DIGE",
      posttranslationally modified proteins are metabolically labeled with azido
      substrate analogs, then size- and charge-matched alkyne-Cy3 or alkyne-Cy5 dyes
      are covalently attached to the azide of the PTM by click chemistry. The
      fluorescently-tagged protein samples are then multiplexed for 2DE analysis.
      Whereas standard DIGE labels all proteins, Click-DIGE focuses the analysis of
      protein differences to a targeted subset of posttranslationally modified proteins
      within a complex sample (i.e. specific labeling and analysis of azido
      glycoproteins within a cell lysate). Our data indicate that (i) Click-DIGE
      specifically labels azido proteins, (ii) the resulting Cy-protein conjugates are
      spectrally distinct, and (iii) the conjugates are size- and charge-matched at the
      level of 2DE. We demonstrate the utility of this approach by detecting multiple
      differentially expressed glycoproteins between a mutant cell line defective in
      UDP-galactose transport and the parental cell line. We anticipate that the
      diversity of azido substrates already available will enable Click-DIGE to be
      compatible with analysis of a wide range of PTMs.

PMID- 24931121
TI  - The parasitophorous vacuole membrane of Toxoplasma gondii is targeted for
      disruption by ubiquitin-like conjugation systems of autophagy.
AB  - Autophagy is a lysosomal degradation pathway that is important in cellular
      homeostasis. Prior work showed a key role for the autophagy related 5 (Atg5) in
      resistance to Toxoplasma gondii. Here we show that the cassette of autophagy
      proteins involved in the conjugation of microtubule-associated protein 1 light
      chain 3 (LC3) to phosphatidylethanolamine, including Atg7, Atg3, and the Atg12
      Atg5-Atg16L1 complex play crucial roles in the control of T. gondii in vitro and
      in vivo. In contrast, pharmacologic modulation of the degradative autophagy
      pathway or genetic deletion of other essential autophagy genes had no substantial
      effects. Rather the conjugation system was required for targeting of LC3 and
      interferon-gamma effectors onto the vacuolar membrane of T. gondii and its
      consequent disruption. These data suggest that the ubiquitin-like conjugation
      systems that reorganize intracellular membranes during canonical autophagy are
      necessary for proper targeting of immune effectors to the intracellular vacuole
      membranes utilized by pathogens. 

PMID- 24931124
TI  - Light-up fluorescent probes utilizing binding behavior of perylenediimide
      derivatives to a hydrophobic pocket within DNA.
AB  - Here we study the binding behavior of perylenediimide () derivatives to a
      hydrophobic pocket created inside DNA and their photochemical properties capable
      of designing a light-up fluorescent sensor for short single-stranded DNA or RNA.
      The perylenediimide derivative with alkoxy groups () suppressing electron
      transfer quenching was examined. The bound randomly to DNA showed negligible
      fluorescence due to the aggregation-induced quenching, whereas the bound to the
      pocket as a monomeric form showed more than 100-fold fluorescence enhancement.
      Switching the binding states of the corresponded to a change in the fluorescence
      response for the hybridization event, which allowed us to design a fluorescent
      sensor of nucleic acids with a nanomolar detection limit. 

PMID- 24931122
TI  - Memory-T-cell-derived interferon-gamma instructs potent innate cell activation
      for protective immunity.
AB  - Cells of the innate immune system are essential for host defenses against primary
      microbial pathogen infections, yet their involvement in effective memory
      responses of vaccinated individuals has been poorly investigated. Here we show
      that memory T cells instruct innate cells to become potent effector cells in a
      systemic and a mucosal model of infection. Memory T cells controlled phagocyte,
      dendritic cell, and NK or NK T cell mobilization and induction of a strong
      program of differentiation, which included their expression of effector cytokines
      and microbicidal pathways, all of which were delayed in nonvaccinated hosts.
      Disruption of IFN-gamma signaling in Ly6C+ monocytes, dendritic cells, and
      macrophages impaired these processes and the control of pathogen growth. These
      results reveal how memory T cells, through rapid secretion of IFN-gamma,
      orchestrate extensive modifications of host innate immune responses that are
      essential for effective protection of vaccinated hosts.

PMID- 24931126
TI  - Dimerization of pyramidalized 3,4,8,9-tetramethyltetracyclo
      [4.4.0.0(3,9).0(4,8)]dec-1(6)-ene to a hydrocarbon featuring four cyclohexane
      rings in boat conformations.
AB  - The synthesis, chemical trapping, and dimerization of a highly pyramidalized
      alkene is reported. Its dimer is a unique nonacycle featuring three planar
      cyclobutane rings, four cyclopentane rings, and four cyclohexane rings in boat
      conformations. The X-ray diffraction analysis showed a H-H distance between the
      flagpole hydrogen atoms of 1.999 A and a separation of 2.619 A between the two
      flagpole carbon atoms. The three cyclobutane rings of the dimer were thermally
      stable. 

PMID- 24931123
TI  - Antiviral activity of human OASL protein is mediated by enhancing signaling of
      the RIG-I RNA sensor.
AB  - Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG
      I, also known as DDX58), which requires RNA and polyubiquitin binding to induce
      type I interferon (IFN) and activate cellular innate immunity. We show that the
      human IFN-inducible oligoadenylate synthetases-like (OASL) protein has antiviral
      activity and mediates RIG-I activation by mimicking polyubiquitin. Loss of OASL
      expression reduced RIG-I signaling and enhanced virus replication in human cells.
      Conversely, OASL expression suppressed replication of a number of viruses in a
      RIG-I-dependent manner and enhanced RIG-I-mediated IFN induction. OASL interacted
      and colocalized with RIG-I, and through its C-terminal ubiquitin-like domain
      specifically enhanced RIG-I signaling. Bone-marrow-derived macrophages from mice
      deficient for Oasl2 showed that among the two mouse orthologs of human OASL,
      Oasl2 is functionally similar to human OASL. Our findings show a mechanism by
      which human OASL contributes to host antiviral responses by enhancing RIG-I
      activation. 

PMID- 24931125
TI  - The Ca2+ sensor S100A1 modulates neuroinflammation, histopathology and Akt
      activity in the PSAPP Alzheimer's disease mouse model.
AB  - The contribution of the Ca(2+) sensor S100A1 to in vivo Alzheimer's disease (AD)
      pathobiology has not been elucidated although S100A1 regulates numerous cellular
      processes linked to AD. This study uses genetic ablation to ascertain the effects
      of S100A1 on neuroinflammation, beta-amyloid (Abeta) plaque deposition and Akt
      activity in the PSAPP AD mouse model. PSAPP/S100A1(-/-) mice exhibited decreases
      in astrocytosis (GFAP burden), microgliosis (Iba1 burden) and plaque load/number
      when compared to PSAPP/S100A1(+/+) mice at six and twelve months of age. The
      presence of detectable S100A1 staining in human AD specimens is consistent with a
      detrimental gain of S100A1 function in AD. S100A1 ablation also reduced plaque
      associated and increased non-plaque associated PO4-Akt and PO4-GSK3beta staining.
      S100A1.Akt complexes were undetectable in PC12 cells and AD brain tissue
      suggesting that S100A1 indirectly modulates Akt activity. In contrast, S100A1.RyR
      (ryanodine receptor) complexes were present in human/mouse AD brain and exhibited
      Ca(2+)-dependent formation in neuronal cells. This is the first direct
      demonstration of an S100A1. target protein complex in tissue/cells and identifies
      the RyR as a primary S100A1 target protein in the brain. Collectively, these data
      suggest that S100A1 inhibition may be a novel strategy for normalizing aberrant
      Ca(2+) signaling in AD. 

PMID- 24931127
TI  - Medication level variability index predicts rejection, possibly due to
      nonadherence, in adult liver transplant recipients.
AB  - Nonadherence to immunosuppressants may play a role in late rejection in liver
      transplant recipients. In children, emerging data suggest that adherence can be
      measured through the computation of the standard deviation (SD) of consecutive
      blood levels of tacrolimus, which results in a number that reflects the degree of
      variability between individual measures: the medication level variability index
      (MLVI). A higher MLVI value means erratic immunosuppression, likely due to less
      adherence. Data on this method are limited for adults. We obtained data from the
      medical charts of 150 randomly selected adult recipients. The MLVI was
      significantly higher for patients who had biopsy-confirmed rejection (mean MLVI =
      3.8, SD = 3.2) versus the rest of the cohort (mean MLVI = 2.3, SD = 1.5, P =
      0.003), and it was significantly higher for patients who suffered rejection
      versus patients whose biopsy sample was not read as rejection (mean MLVI = 2.6,
      SD = 1.6, P = 0.008). The MLVI was associated with rejection and predicted its
      occurrence. A threshold MLVI of 2.0 resulted in 77% sensitivity and 60%
      specificity in predicting rejection; a threshold of 1.8 resulted in a sensitivity
      of 92% and a specificity of 48%. The area under the curve in a receiver operating
      characteristic curve analysis was 0.71 (95% CI = 0.61-0.81). In conclusion, the
      MLVI is associated with and can predict rejection, possibly related to
      nonadherence, in adult liver transplant recipients.

PMID- 24931128
TI  - Seroprevalence of enteropathogenic Yersinia spp. in pig batches at slaughter.
AB  - Enteropathogenic Yersinia spp. are one of the main causes of foodborne bacterial
      infections in Europe. Slaughter pigs are the main reservoir and carcasses are
      contaminated during a sub-optimal hygienically slaughtering-process. Serology is
      potentially an easy option to test for the Yersinia-status of the pig (batches)
      before slaughter. A study of the variation in activity values (OD%) of Yersinia
      spp. in pigs and pig batches when applying a serological test were therefore
      conducted. In this study, pieces of the diaphragm of 7047 pigs, originating from
      100 farms, were collected and meat juice was gathered, where after an enzyme
      linked immunosorbent assay (ELISA) Pigtype Yopscreen (Labor Diagnostik Leipzig,
      Qiagen, Leipzig, Germany) was performed. The results were defined positive if the
      activity values exceeded the proposed cut-off value of 30 OD%. Results at pig
      level displayed a bimodal-shaped distribution with modes at 0-10% (n=879) and 50
      60% (n=667). The average OD% was 51% and 66% of the animals tested positive. The
      within-batch seroprevalence ranged from 0 to 100% and also showed a bimodal
      distribution with modes at 0% (n=7) and 85-90% (n=16). On 7 farms, no single
      seropositive animal was present and in 22 farms, the mean OD% was below 30%.
      Based on the results obtained at slaughter, 66% of the pigs had contact with
      enteropathogenic Yersinia spp. at farm level. The latter occurred in at least 93%
      of the farms indicating that most farms are harboring enteropathogenic Yersinia
      spp. 

PMID- 24931129
TI  - Comparison of time to PRRSv-stability and production losses between two exposure
      programs to control PRRSv in sow herds.
AB  - To control and eliminate porcine reproductive and respiratory syndrome virus
      (PRRSv) from breeding herds, some veterinarians adopt a strategy called load
      close-expose which consists of interrupting replacement pig introduction for
      several months and exposing the pigs to a replicating PRRSv. This was a
      prospective quasi-experiment that followed 61 breeding herds acutely infected
      with PRRSv that adopted one of two exposure programs: modified-live virus (MLV)
      vaccine or live-resident virus inoculation (LVI). Treatment groups (load-close
      expose with MLV or LVI) were compared for: (a) time-to-PRRSv stability (TTS),
      defined as time in weeks it took to produce PRRSv negative pigs at weaning; (b)
      the time-to-baseline production (TTBP), defined using statistical process control
      methods to represent time to recover to the number of pigs weaned per week that
      herds had prior to PRRSv-detection; and (c) the total production loss in terms of
      number of pigs weaned per week. TTS and TTBP were compared between treatments
      using survival analysis. Day 1 of the program was considered to be the day that
      treatment was administered. Sampling at herds consisted of bleeding 30 due-to
      wean piglets on a monthly basis. Serum was tested for PRRSv RNA by RT-PCR. Herds
      in which PRRSv was not detected over a 90-day period were classified as reaching
      stability. Multivariate analysis using proportional hazards regression was
      performed adjusting the effect of treatment on TTBP and TTS to 'severity of PRRSv
      infection', 'number of whole-herd exposures', 'days from PRRSv-detection to
      intervention', 'prior PRRSv-infection status' and 'veterinary clinic associated
      with the herd'. Total loss was compared between groups using multivariate
      regression analysis adjusted by selected covariates. The median TTS among
      participating herds was 26.6 weeks (25th to 75th percentile, 21.6-33.0 weeks).
      The overall TTBP was 16.5 weeks (range 0-29 weeks). The magnitude of production
      losses following whole-herd exposure averaged 2217 pigs not weaned/1000 sows and
      was correlated with TTBP. Herds in the MLV group recovered production sooner and
      had less total loss than herds in the LVI group. TTBP and TTS were significantly
      shorter and the total loss was significantly less in herds assisted by a specific
      veterinary clinic and herds that were infected with PRRSv in the 3 years prior to
      the study. This study provided new metrics to assist veterinarians to decide
      between methods of exposure to control and eliminate PRRSv from breeding herds. 

PMID- 24931130
TI  - Seroprevalence of Anaplasma marginale in Texas cattle.
AB  - To our knowledge the seroprevalence of Anaplasma marginale in Texas has not been
      reported. The objective of this study was to estimate the point seroprevalence
      and spatial distribution of Texas cattle persistently infected with A. marginale.
      This was a cross-sectional observational study examining serum collected from
      12,000 adult cattle marketed in 23 selected Texas auction markets during the
      second week of July 2011. A random subset of those cattle comprising 1835
      individuals was evaluated for persistent infection with A. marginale using a
      commercial cELISA for antibody detection. The pooled apparent seroprevalence for
      cattle tested at auction markets across the state was 15.02% (95% CI: 11.02
      19.53%), with markets in the western portion of the state demonstrating
      prevalence => 30%. The winter tick, Dermacentor albipictus is involved in the
      biological transfer of A. marginale and is prevalent in west Texas. Producers in
      endemic and non-endemic areas should be encouraged to determine the infection
      status of replacement cattle in order to implement effective management
      strategies for the control bovine anaplasmosis.

PMID- 24931132
TI  - Evaluation of new Deflux administration techniques: intraureteric HIT and Double
      HIT for the endoscopic correction of vesicoureteral reflux.
AB  - Vesicoureteral reflux (VUR) is one of the most common urologic diagnoses
      affecting children, and optimal treatment requires an individualized approach
      that considers potential risks. Management options include observation with or
      without continuous antibiotic prophylaxis and surgical correction via endoscopic,
      open or laparoscopic/robotic approaches. Endoscopic correction of VUR is an
      outpatient procedure associated with decreased morbidity compared with ureteral
      reimplantation. The concept of ureteral hydrodistention and intraluminal
      submucosal injection (Hydrodistention Implantation Technique [HIT]) has led to
      improved success rates in eliminating VUR compared with the subureteral
      transurethral injection technique. Further modifications now include use of
      proximal and distal intraluminal injections (Double HIT) that result in
      coaptation of both the ureteral tunnel and orifice. Endoscopic injection of
      dextranomer/hyaluronic acid copolymer, via the HIT and Double HIT, has emerged as
      a highly successful, minimally invasive alternative to open surgical correction,
      with minimal associated morbidity. 

PMID- 24931131
TI  - An acute-phase protein as a regulator of sperm survival in the bovine oviduct:
      alpha 1-acid-glycoprotein impairs neutrophil phagocytosis of sperm in vitro.
AB  - We have previously shown that polymorphonuclear neutrophils (PMNs) are present in
      bovine oviduct fluid under physiological conditions, and that the oviduct
      provides a microenvironment that protects sperm from phagocytosis by PMNs. Alpha
      1-acid glycoprotein (AGP) is a major acute-phase protein produced mainly in the
      liver that has immunomodulatory functions. AGP mRNA is expressed in extrahepatic
      organs, such as the lung, kidney, spleen, lymph node, uterus, and ovary.
      Therefore, in this study, we investigated, 1) the local production of AGP in the
      bovine oviduct, 2) the effect of AGP on the phagocytic activity of PMNs for sperm
      and superoxide production and 3) the impact of AGP desialylation on the PMN
      phagocytosis of sperm. The AGP gene was expressed in cultured bovine oviduct
      epithelial cells (BOECs) and AGP protein was detected in oviduct fluid.
      Preexposure of PMNs to AGP at physiological levels impaired PMN phagocytosis for
      sperm and superoxide generation. The desialylation of AGP eliminated these
      suppressive effects of AGP on PMN. Scanning electron microscopy revealed that AGP
      drastically reduced the formation of DNA-based neutrophil extracellular traps
      (NETs) for sperm entanglement. Additionally, AGP dose-dependently stimulated
      BOECs to produce prostaglandin E2 (PGE2) which has been shown to partially
      contribute to the regulation of sperm phagocytosis in the bovine oviduct. AGP and
      PGE2 at concentrations detected in the oviducts additively suppressed sperm
      phagocytosis by PMNs. These results provide evidence that locally produced AGP
      may be involved in protecting sperm from phagocytosis by PMNs in the bovine
      oviduct. 

PMID- 24931133
TI  - [Analysis of the sono-anatomy of the nerve plexus using telemedicine from a
      combat zone].

PMID- 24931134
TI  - [Prophylactic use of icatibant before tracheal intubation of a patient with
      hereditary angioedema type III. (A literature review of perioperative management
      of patients with hereditary angioedema type III)].
AB  - Type III hereditary angioedema is a rare familial disorder that has recently been
      described as a separate condition. Triggers for episodes of angioedema include
      surgery, dental procedures, and tracheal intubation maneuvers. Since episodes
      affecting the upper airway are potentially life-threatening, prophylactic
      treatment is recommended in these situations. The use of icatibant
      (Firazyr((r))), for prevention of angioedema prior to tracheal intubation, is
      reported in a patient with type iii hereditary angioedema. A literature review on
      the anesthetic management of this condition was conducted. 

PMID- 24931135
TI  - Hepatic and pancreatic resection in patients with end-stage renal disease: a
      propensity analysis.
AB  - BACKGROUND: Hepatic and pancreatic surgery is rarely performed in patients with
      end-stage renal disease (ESRD). The present authors used a national clinical
      database to characterize outcomes and perioperative risk in ESRD patients who
      require hepatic or pancreatic resection. METHODS: The 2005-2011 National Surgical
      Quality Improvement Program database was queried for all patients undergoing
      hepatic or pancreatic resection. Patients were classified by the presence or
      absence of ESRD. The independent effects of ESRD on outcomes were assessed after
      propensity score adjustment and multivariable logistic regression. RESULTS: Of
      the 27 376 patients submitted to hepatic or pancreatic procedures identified in
      the database, 101 patients were found to have preoperative ESRD. Patients with
      ESRD experienced perioperative mortality at a rate similar to that in those
      without ESRD (5.0% versus 2.3%; P = 0.08). After risk adjustment, the presence of
      ESRD was associated with three-fold higher odds of postoperative sepsis (adjusted
      odds ratio: 2.98, P = 0.014), but no significant differences in mortality or
      major complication rates. CONCLUSIONS: Hepatic and pancreatic resections can be
      performed safely in selected patients with ESRD. These patients may have an
      increased risk for the development of postoperative sepsis. Further study is
      needed to characterize modifiable risk factors that impact outcomes in patients
      with ESRD who require hepatic or pancreatic resection.

PMID- 24931136
TI  - Free amino acids in stimulated and unstimulated whole saliva: advantages or
      disadvantages.
AB  - This study determines the mean concentrations of free amino acids in stimulated
      and unstimulated whole saliva in healthy young adults. Standardised salivary
      amino acids as a substitute for their counterpart in blood, searched for the
      source of free amino acids in saliva, the probable correlation between particular
      amino acids with caries experience. Stimulated and unstimulated whole saliva were
      collected by the draining method in 31 dental students. Saliva was purified, and
      amino acids were separated by high-performance liquid chromatography. DMFT scores
      were recorded, and the relation of amino acids to caries experience was explored
      by generalised linear model. Almost all amino acids had higher concentration in
      unstimulated whole saliva than in stimulated saliva. The normal range of amino
      acids (95% CI) and their natural logarithm were defined. There was a significant
      relationship between caries experience and threonine (P < 0.008), citrulline (P <
      0.023) and ornithine (P < 0.001) as a detrimental factor, whereas serin (P <
      0.026), glutamine (P < 0.015) and phenylalanine (P < 0.014) had an inhibiting
      effect on caries. However, in comparison, salivary flow rate (P < 0.013) was a
      more preventive factor than amino acids. Amino acids in saliva contribute as a
      marker, instead of their counterpart in blood. Unstimulated saliva had higher
      concentration of amino acids. Amino acids have different impact on caries and may
      be one of underlying risk factors for caries experience. 

PMID- 24931137
TI  - Quantity and diversity of environmental microbial exposure and development of
      asthma: a birth cohort study.
AB  - BACKGROUND: Early-life exposure to environmental microbial agents may be
      associated with the development of allergies. The aim of the study was to
      identify better ways to characterize microbial exposure as a predictor of
      respiratory symptoms and allergies. METHODS: A birth cohort of 410 children was
      followed up until 6 years of age. Bacterial endotoxin, 3-hydroxy fatty acids, N
      acetyl-muramic acid, fungal extracellular polysaccharides (EPS) from Penicillium
      and Aspergillus spp., beta-D-glucan, ergosterol, and bacterial or fungal
      quantitative polymerase chain reactions (qPCRs) were analyzed from dust samples
      collected at 2 months of age. Asthma, wheezing, cough, and atopic dermatitis were
      assessed using repeated questionnaires. Specific IgEs were determined at the age
      of 1 and 6 years. RESULTS: Only few associations were found between single
      microbial markers and the studied outcomes. In contrast, a score for the total
      quantity of microbial exposure, that is, sum of indicators for fungi
      (ergosterol), Gram-positive (muramic acid) bacteria, and Gram-negative
      (endotoxin) bacteria, was significantly (inverted-U shape) associated with asthma
      incidence (P < 0.001): the highest risk was found at medium levels (adjusted odds
      ratio (aOR) 2.24, 95% confidence interval (95% CI) 0.87-5.75 for 3rd quintile)
      and the lowest risk at the highest level (aOR 0.34, 95% CI 0.09-1.36 for 5th
      quintile). The microbial diversity score, that is, sum of detected qPCRs, was
      inversely associated with risk of wheezing and was significantly (inverted-U
      shape) associated with sensitization to inhalant allergens. CONCLUSION: Score for
      quantity of microbial exposure predicted asthma better than single microbial
      markers independently of microbial diversity and amount of dust. Better
      indicators of total quantity and diversity of microbial exposure are needed in
      studies on the development of asthma.

PMID- 24931139
TI  - Protein expression of various hepatic uridine 5'-diphosphate
      glucuronosyltransferase (UGT) enzymes and their inter-correlations: a meta
      analysis.
AB  - Avoiding cytochrome P450 (CYP) related drug interactions in the development of
      new drug candidates means that glucuronidation by uridine 5'-diphosphate
      glucuronosyltransferase (UGT) enzymes is expected to become a more prominent
      pathway in the metabolism of new drug candidates designed by pharmaceutical
      companies. Therefore, determining the abundance and activity of these enzymes is
      of value in the process of scaling in vitro data to in vivo metabolic parameters.
      Many of the studies involving the measurement of UGTs were conducted with too few
      samples, which did not provide a good indication of population values and the
      level of variability. Meta-analysis is used in the current study to combine all
      reported values (eight studies that used LC-MS isotope-labelled standard targeted
      quantitative methods), detect inconsistencies between the various datasets and
      describe correlations of expression between the quantified UGT enzymes. Some
      heterogeneity was observed between studies, especially in the UGT1A4, 2B7 and
      2B10 datasets. However, in the absence of information on the inter-laboratory
      consistency of assays, it is difficult to assign these differences to the
      heterogeneity of the samples. Large inter-individual variability was observed in
      the collated data across this family of enzymes. Positive correlations between
      the expression levels of certain UGT enzymes were found in the collated data.
      These included the pairs: UGT1A4/2B4 (rs=0.71, p<0.0001, n=82), UGT2B4/2B15
      (rs=0.63, p<0.0001, n=83), UGT2B7/2B15 (rs=0.81, p<0.0001, n=99). These
      correlations can be explained by common regulatory mechanisms involved in the
      expression of these proteins.

PMID- 24931140
TI  - Significance of longitudinal changes in the default-mode network for cognitive
      recovery after stroke.
AB  - Although a considerable number of patients suffer from cognitive impairments
      after stroke, the neural mechanism of cognitive recovery has not yet been
      clarified. Repeated resting-state functional magnetic resonance imaging (fMRI)
      was used in this study to examine longitudinal changes in the default-mode
      network (DMN) during the 6 months after stroke, and to investigate the
      relationship between DMN changes and cognitive recovery. Out of 24 initially
      recruited right-hemispheric stroke patients, 11 (eight males, mean age 55.7
      years) successfully completed the repeated fMRI protocol. Patients underwent
      three fMRI sessions at 1, 3 and 6 months after stroke. Their DMNs were analysed
      and compared with those of 11 age-matched healthy subjects (nine males, mean age
      56.2 years). Correlations between DMN connectivity and improvement of the
      cognitive performance scores were also assessed. The stroke patients were found
      to demonstrate markedly decreased DMN connectivity of the posterior cingulate
      cortex, precuneus, medial frontal gyrus and inferior parietal lobes at 1 month
      after stroke. At 3 months after stroke, the DMN connectivity of these brain areas
      was almost restored, suggesting that the period is critical for neural
      reorganization. The DMN connectivity of the dorsolateral prefrontal cortex in the
      contralesional hemisphere showed a significant correlation with cognitive
      function recovery in stroke patients, and should be considered a compensatory
      process for overcoming cognitive impairment due to brain lesion. This is the
      first longitudinal study to demonstrate the changes in DMN during recovery after
      stroke and the key regions influencing cognitive recovery. 

PMID- 24931138
TI  - Coverage of protein domain families with structural protein-protein interactions:
      current progress and future trends.
AB  - Protein interactions have evolved into highly precise and regulated networks
      adding an immense layer of complexity to cellular systems. The most accurate
      atomistic description of protein binding sites can be obtained directly from
      structures of protein complexes. The availability of structurally characterized
      protein interfaces significantly improves our understanding of interactomes, and
      the progress in structural characterization of protein-protein interactions
      (PPIs) can be measured by calculating the structural coverage of protein domain
      families. We analyze the coverage of protein domain families (defined according
      to CDD and Pfam databases) by structures, structural protein-protein complexes
      and unique protein binding sites. Structural PPI coverage of currently available
      protein families is about 30% without any signs of saturation in coverage growth
      dynamics. Given the current growth rates of domain databases and structural PPI
      deposition, complete domain coverage with PPIs is not expected in the near
      future. As a result of this study we identify families without any protein
      protein interaction evidence (listed on a supporting website
      http://www.ncbi.nlm.nih.gov/Structure/ibis/coverage/) and propose them as
      potential targets for structural studies with a focus on protein interactions. 

PMID- 24931141
TI  - Unraveling cellular phenotypes of novel TorsinA/TOR1A mutations.
AB  - A three-nucleotide (GAG) deletion (DeltaE) in TorsinA (TOR1A) has been identified
      as the most common cause of dominantly inherited early-onset torsion dystonia
      (DYT1). TOR1A encodes a chaperone-like AAA+-protein localized in the endoplasmic
      reticulum. Currently, only three additional, likely mutations have been reported
      in single dystonia patients. Here, we report two new, putative TOR1A mutations
      (p.A14_P15del and p.E121K) that we examined functionally in comparison with wild
      type (WT) protein and two known mutations (DeltaE and p.R288Q). While inclusion
      formation is a characteristic feature for DeltaE TOR1A, elevated levels of
      aggregates for other mutations were not observed when compared with WT TOR1A. WT
      and mutant TOR1A showed preferred degradation through the autophagy-lysosome
      pathway, which is most pronounced for p.A14_P15del, p.R288Q, and DeltaE TOR1A.
      Notably, blocking of the autophagy pathway with bafilomycin resulted in a
      significant increase in inclusion formation in p.E121K TOR1A. In addition, all
      variants had an influence on protein stability. Although the p.A14_P15del
      mutation affects the proposed oligomerization domain of TOR1A, this mutation did
      not disturb the ability to dimerize. Our findings demonstrate functional changes
      for all four mutations on different levels. Thus, both diagnostic and research
      genetic screening of dystonia patients should not be limited to testing for the
      ?E mutation. 

PMID- 24931143
TI  - Key processes in ruthenium-catalysed olefin metathesis.
AB  - While the fundamental series of [2+2]cycloadditions and retro[2+2]cycloadditions
      that make up the pathways of ruthenium-catalysed metathesis reactions is well
      established, the exploration of mechanistic aspects of alkene metathesis
      continues. In this Feature Article, modern mechanistic studies of the alkene
      metathesis reaction, catalysed by well-defined ruthenium complexes, are
      discussed. Broadly, these concern the processes of pre-catalyst initiation,
      propagation and decomposition, which all have a considerable impact on the
      overall efficiency of metathesis reactions. 

PMID- 24931142
TI  - Identification of novel therapeutic targets in the PI3K/AKT/mTOR pathway in
      hepatocellular carcinoma using targeted next generation sequencing.
AB  - Understanding genetic aberrations in cancer leads to discovery of new targets for
      cancer therapies. The genomic landscape of hepatocellular carcinoma (HCC) has not
      been fully described. Therefore, patients with refractory advanced/metastatic HCC
      referred for experimental therapies, who had adequate tumor tissue available, had
      targeted next generation sequencing (NGS) of their tumor samples using the
      Illumina HiSeq 2000 platform (Foundation One, Foundation Medicine, MA) and their
      treatment outcomes were analyzed. In total, NGS was obtained for 14 patients
      (median number of prior therapies, 1) with advanced/metastatic HCC. Of these 14
      patients, 10 (71%) were men, 4 (29%) women, 6 (43%) had hepatitis B or C-related
      HCC. NGS revealed at least 1 molecular abnormality in 12 patients (range 0-8,
      median 2). Detected molecular aberrations led to putative activation of the
      PI3K/AKT/mTOR pathway (n=3 [mTOR, PIK3CA, NF1]), Wnt pathway (n=6 [CTNNA1,
      CTNNB1]), MAPK pathway (n=2 [MAP2K1, NRAS]), and aberrant DNA repair mechanisms,
      cell cycle control and apoptosis (n=18 [ATM, ATR, BAP1, CCND1, CDKN2A, CDK4,
      FGF3, FGF4, FGF19, MCL1, MDM2, RB1, TP53]). Of the 3 patients with molecular
      aberrations putatively activating the PI3K/AKT/mTOR pathway, 2 received therapies
      including a mTOR inhibitor and all demonstrated therapeutic benefit ranging from
      a partial response to minor shrinkage per RECIST (-30%, -15%; respectively). In
      conclusion, genomic alterations are common in advanced HCC. Refractory patients
      with alterations putatively activating the PI3K/AKT/mTOR pathway demonstrated
      early signals of clinical activity when treated with therapies targeting mTOR. 

PMID- 24931144
TI  - Validation of the Maryland Aggregate Pathology Index (MAPI), a pre-implantation
      scoring system that predicts graft outcome.
AB  - Predicting graft outcome after renal transplantation based on donor histological
      features has remained elusive and is subject to institutional variability. We
      have shown in a retrospective study that the Maryland Aggregate Pathology Index
      score reliably predicts graft outcome. We sought to validate the scoring system
      in our center and a second transplant center. We analyzed 140 deceased donor
      kidneys pre-implantation biopsies from center 1 and 65 from center 2. The
      patients had a mean follow-up of 695 +/- 424 and 656 +/- 305 d respectively.
      Although MAPI scores were similar, there were significant differences in donor
      and recipient parameters between both centers. Despite this, MAPI was predictive
      of graft outcome for both centers by Cox univariate, multivariate and time
      dependent ROC analysis. For center 1 and 2, three yr graft survival within each
      MAPI group was statistically equivalent. The three-yr graft survival at center 1
      for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%,
      respectively, p <= 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p =
      0.006. MAPI, which is based on a pre-implantation biopsy, demonstrated similar
      predictive and outcome results from both centers. As expanded criteria donors
      (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further
      define ECD kidneys, increase utilization, and ultimately improve outcomes.

PMID- 24931145
TI  - Age-specific reference range of prostate-specific antigen and prostate cancer
      detection in population-based screening cohort in Japan: verification of Japanese
      Urological Association Guideline for prostate cancer.
AB  - OBJECTIVES: To investigate the age-specific reference range of prostate-specific
      antigen and clinical characteristics of screening-detected cancer in prostate
      specific antigen-based screening, and to verify the age-specific prostate
      specific antigen cut-offs in the Japanese Urological Association Guidelines.
      METHODS: Prostate-specific antigen distributions were estimated in a total of
      69,028 screening tests according to the age of the participants in population
      screening from 2000 to 2013. The age-specific reference range of prostate
      specific antigen for detection of cancer was investigated by analyzing the
      receiver operating characteristic curves. Furthermore, the clinicopathological
      features of screening-detected cancer with serum prostate-specific antigen levels
      below the age-specific prostate-specific antigen cut-off in the Japanese
      Urological Association Guidelines were also investigated. RESULTS: Of all 69,028
      screens, 2053 prostate biopsies (2.97%) were carried out and 549 cases of cancer
      (0.79%) were diagnosed. The 95th percentiles in all participants aged 54-59, 60
      64, 65-69 and 70-75 years old were 2.90, 3.60, 4.10, and 4.70 ng/mL,
      respectively. The optimal prostate-specific antigen cut-offs for cancer detection
      determined from the receiver operating characteristic curves were 2.3 and 2.6 for
      the age ranges 54-69 and 70-75 years, respectively. These values were lower than
      the age-specific cut-offs in the Japanese Urological Association Guidelines. Of
      all 137 patients with prostate-specific antigen levels below the age-specific cut
      offs in the Japanese Urological Association Guidelines, 80 (58.4%) had
      unfavorable clinicopathological features as active surveillance criteria.
      CONCLUSIONS: The age-specific reference range of prostate-specific antigen might
      be lower than that recommended in the Japanese Urological Association Guidelines.
      An individualized and natural history-adjusted screening system should be
      established for screening participants with low prostate-specific antigen level.

PMID- 24931147
TI  - [Rational performance of femtosecond laser assisted corneal refractive surgery
      against complication].
AB  - Many clinical data have shown that the femtosecond assisted corneal refractive
      surgery is a safe and effective method for ammetropia. The perfect visual quality
      of post-operation must be achieved due to high price and high expectation from
      patients. Therefore, surgeons should select the indication carefully, pay more
      attention on procedure carefully and prevent from complications perioperative
      period. Some strategies on the key points are stated in this article in order to
      avoiding the complications related to femtosecond assisted corneal refractive
      surgery, to eliminating the potential medical trap and approaching to the perfect
      visual quality. 

PMID- 24931146
TI  - Chemical composition, antioxidant activities and protein profiling of different
      parts of Allamanda cathartica.
AB  - The phytochemical screening and protein profiling of Allamanda cathartica was
      performed. Biochemical analysis revealed that peroxidase (8730 +/- 307 units/g),
      superoxide dismutase (181 +/- 3.79 units/g), catalase (529 +/- 28.9 units/g),
      protease (3598 +/- 79.8 units/g), total phenolic contents (19,344 +/- 657 MUM/g),
      beta-esterases (342 +/- 46.5 units/g) and the total oxidant status were highest
      in the roots as compared to other plant parts. However, total soluble proteins
      (128 +/- 1.54 mg/g), lycopene (5.70 +/- 0.61 mg/g), chlorophyll a (161 +/- 24.9
      MUg/g), total chlorophyll content (267 +/- 34.3 MUg/g) and total carotenoid
      content (12.4 +/- 1.71 mg/g) were found to be highest in leaves. Moreover, total
      antioxidant capacity (5.43 +/- 0.29 MUM/g) detected by using ABTS method and
      alpha-esterase (714.580 +/- 23.6 units/g) were highest in shoots. The protein
      profiling was performed using SDS-PAGE. In leaves, 13 peptides with molecular
      weight (M.wt.) from 27 to 168 kDa were detected while in shoots 10 peptides with
      M.wt. from 30 to 95 kDa were resolved. Similarly, in roots, 10 peptides of 30-880
      kDa and in flower seven peptides of 30-88 kDa were detected. 

PMID- 24931148
TI  - [Perioperative ocular surface evaluation and management in meibomian gland
      dysfunction patients undergoing cataract surgery].
AB  - Meibomian gland dysfunction (MGD) is one of the most common conditions in the
      elderly. Most of MGD patients undergoing cataract surgery were found to have
      significant dry eye symptoms and ocular surface disease. The severe cases with
      ocular surface disease are also at higher risk of postoperative complications,
      namely infections and corneal ulcers. To improve the operation effect and achieve
      the best visual outcome and life quality in cataract patients, it is important to
      evaluate the ocular surface and meibomian glands in MGD patients preoperatively,
      pay attention to the intraoperative care and detect the postoperative
      complications carefully and use medicine properly. 

PMID- 24931149
TI  - [Evaluation of the diagnostic value for meibomian gland dysfunction
      examinations].
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of clinical examinations
      in meibomian gland dysfunction (MGD). METHODS: A prospective case-controlled
      study. Fifty-two patients with MGD and 32 healthy age- and sex-matched control
      subjects were included from January to August 2013. All subjects were underwent
      the examinations sequentially as follows: evaluation of ocular surface disease
      symptoms using the Ocular Surface Disease Index (OSDI); lid margin and ocular
      surface examination by slit lamp microscrope; infrared meibomian photography;
      cornea sensation testing using the Cochet-Bonnet esthesiometer; tear film break
      up time (BUT); corneal and conjunctival staining (Oxford scale); and Schirmer I
      test. One eye of each subject was included in the study. The parameters between
      MGD group and the control group were compared using the independent-samples T
      test. Spearman's correlation analysis was used to analyze the correlation of each
      parameter of MGD group. Receiver operating characteristic curve (ROC curve) and
      area under the curve (AUC) were used to describe the accuracy of each parameter
      to differentiate MGD from normal eyes. RESULTS: OSDI score, lid margin
      abnormality score, miss rate of meibomian glands and corneal and conjunctival
      staining score were obviously higher in MGD group (36.13 +/- 14.71, 2.37 +/-
      0.937, (52.64 +/- 17.23) %, 1.06 +/- 1.75) than those in control group(5.22 +/-
      11.97, 0.94 +/- 0.564, (23.97 +/- 6.36) %, 0.03 +/- 0.18) (t = 10.019, 7.808,
      8.796, 3.293, respectively; P < 0.01). BUT, schirmer I value and corneal
      sensitivity score were significantly lower in MGD group (4.57 +/- 2.13, 6.04 +/-
      7.09, 5.77 +/- 0.38) than those in control group (13.31 +/- 2.54, 12.56 +/- 6.99,
      5.98 +/- 0.07) (t = -16.97, -4.119, -3.018, respectively; P < 0.01). AUC value of
      BUT was the largest (0.995), and the followings were the miss rate of meibomian
      (0.944), OSDI (0.925) and lid margin abnormalities (0.811). The sensitivity and
      the specificity of BUT were 90.4% and 100.0%; the miss rate of meibomian were
      76.9% and 100.0%; OSDI were 97.4% and 87.1%; and lid margin abnormalities were
      79.5% and 79.4%. The diagnostic value of these four parameters were better than
      the rest ones. CONCLUSION: BUT and the miss rate of meibomian have great value in
      diagnosis of MGD. Patients considered MGD can be performed these examinations to
      confirm the diagnosis.

PMID- 24931150
TI  - [Post operation complications analysis and their treatment of Descemet's
      stripping automated endothelium keratoplasty].
AB  - OBJECTIVE: To summarize intra and post operation complications and their
      treatment of Descemet's Stripping Automated Endothelium Keratoplasty (DSAEK), and
      provide our experience for its development in China. METHODS: Retrospective case
      study. Forty-seven eyes of 42 patients underwent DSAEK performed by one surgeon.
      Indications include: Pseudophakic or aphakic Bullous Keratopathy, 27 eyes
      (57.4%); Fuchs Endothelial Dystrophy, 7 eyes (14.9%); endothelial decompensation
      post vitrectomy, 3 eyes (6.4%); iridocorneal endothelial syndrome (ICE), 3 eyes
      (6.4%); congenital glaucoma, 3 eyes (6.4%); graft failure post endothelial
      keratoplasty, 3 eyes (6.4%); endothelial decompensation after open ocular injury
      and intraocular foreign body, 1 eye (2.1%). Nineteen eyes underwent single DSAEK
      (40.4%); eight combined phacoemulsification and intraocular lens implantation
      (17.0%); eight combined anterior chamber IOL (AC-IOL) removal plus anterior
      segment vitrectomy and posterior chamber IOL (PC-IOL) implantation (17.0%); eight
      combined anterior segment vitrectomy and PC-IOL suspension (17.0%); two combined
      cataract extraction and anterior segment vitrectomy (4.3%); two failed in DSAEK
      and underwent penetrating keratoplasty (4.3%). RESULTS: Dislocation is the most
      common postoperative complications. Ten eyes underwent dislocation in 47 eyes
      (21.3%), which was solved by air and viscoelastic agent injection. High
      intraocular pressure happened in 12 eyes (25.5%), in 11 of which had a history of
      glaucoma and 1 with ICE. After drug treatment, ten patients had stable
      intraocular pressure and two patients underwent ciliary body photocoagulation
      surgery (1 case with anterior chamber intraocular lens, 1 case with ICE).
      Reactions happened in 2 cases (4.3%) patients, including 1 case with anterior
      chamber IOL (AC-IOL) rehabilitating after drug treatment and the other with
      Fuch's corneal endothelial dysfunction being regrafted. CONCLUSION: Dislocation
      is the most common complication after corneal endothelial keratoplasty, and air
      injection in anterior chamber is a common and effective method; High intraocular
      pressure is the second postoperative complication. Preoperative history of
      glaucoma is closely related to postoperative high intraocular pressure.

PMID- 24931152
TI  - [The clinical results of femtosecond laser-assisted deep anterior lamellar
      keratoplasty in patients with keratoconus].
AB  - OBJECTIVE: To evaluate the clinical results and safety of deep anterior lamellar
      keratoplasty (DALK) in patients with keratoconus assisted by a femtosecond laser.
      METHODS: Six eyes of 5 patients with keratoconus underwent DALK procedures by
      using a femtosecond laser. The mean thinnest corneal thickness, evaluated with
      ultrasound and measurement of visual acuity by using the standard logarithm
      visual chart. A femtosecond laser was used to perform corneal cuts on both donor
      and recipient corneas. The data were expressed as mean +/- SD. Mean follow-up was
      (8.9 +/- 2.3) month (range, 5-12 months) . RESULTS: Corneal pachymetry was (385
      +/- 48) um (range, 380-460 um) . Mean preoperative uncorrected visual acuity was
      0.06 +/- 0.06 (range,0.01-0.15) and mean preoperative best spectacle-corrected
      visual acuity was 0.41 +/- 0.35 (range,0.12-1.00) . The donor corneal lamella
      diameters were 0.20 mm larger and thicker than the recipient to restore a
      physiologic corneal thickness and shape. Mean donor diameter was (7.8 +/- 0.2) mm
      (range, 7.3-8.0 mm) and mean thickness was (372 +/- 40) um (range, 350-400 um)
      .Early postoperative evaluation showed a clear graft in all cases. Mean corneal
      thickness was (459 +/- 36) um (range, 389-488 um) . At the last postoperative
      examination mean uncorrected visual acuity was 0.32 +/- 0.19 (range, 0.12-0.60) ,
      and the mean best corrected visual acuity was 0.58 +/- 0.29 (range,0.20-1.00) .
      The UCVA and BCVA improved significantly after surgery (t = -4.433, -3.348, P <
      0.05). CONCLUSIONS: Our early results indicate that femtosecond laser-assisted
      deep anterior lamellar keratoplasty shows promise as a safe and effective
      surgical choice in the treatment of keratoconus.

PMID- 24931151
TI  - [Study on the clinical manifestation of 90 cases with scleritis and
      episcleritis].
AB  - OBJECTIVE: To evaluate the demographic characteristics, clinical features, ocular
      complications, and disease associations of patients who were diagnosed as
      scleritis and episcleritis in clinic. METHODS: A retrospective case series
      study.Ninety patients were diagnosed clinically as scleritis and episcleritis in
      Beijing Tongren Hospital from Jan 2010 to Jan 2013. Analyzed the general states
      of health, case history, the clinical manifestation, clinical features, ocular
      complications (decrease in vision, anterior uveitis, keratitis, ocular
      hypertension, cataract, and diseases of retina), and disease associations, to
      summarize the clinical characteristics of scleritis and episcleritis. RESULTS:
      Ninety patients were recorded, from 4 to 83 years old, and the average was (48 +/
      15) years old. 30 cases (33.3%) were male, and 60 (66.7%) were female. There
      were no significant difference between male and female (chi2 = 10.000, P <
      0.01).In the 90 cases, 36 (40.0%) were episleritis and 54 cases (60.0%) were
      scleritis. Children group (0-16 years old) had 2 cases (2.2%), which all were
      episleritis.Young adult group (17-44 years old) had 39 cases (43.4%), including
      13 were episleritis and 26 cases were scleritis. Middle adult group (45-59 years
      old) had 30 cases, including 9 cases episleritis and 21 cases scleritis. There
      were 19 cases (21.2%) in aged group ( >= 60 years), including 12 cases
      episleritis and 7 scleritis.Young adult group, Middle adult group and Aged group
      were significantly more than Children and aged group (chi2 = 33.390, 24.500 and
      13.762, P < 0.01).Young group was significantly more than Aged group Children
      group (chi2 = 6.889, P < 0.01). Ocular complications were more frequent overall
      in patients with scleritis versus in those with episcleritis (chi2 = 30.044, P <
      0.01) , including decrease in vision, keratitis, and ocular hypertension (chi2 =
      130.200, 67.200, 54.444, P < 0.01) .Nineteen cases (21.1%) had different types of
      arthritis, and 10 cases (11.1%) had infection diseases in local. There were
      difference between episcleritis and scleritis (chi2 = 145.644, P < 0.01) .
      CONCLUSIONS: Scleritis occurs in all ages, but mainly in adults.It is uncommon,
      and potentially life-threatening diseases. It is needed pay attention to
      diagnosis and treatment of the patients with systemic disease and ocular
      complications by Ophthalmologist.

PMID- 24931153
TI  - [Construction of corneal endothelium deficiency model by cryo-injury and its
      application].
AB  - OBJECTIVE: To set up an animal model of corneal endothelium deficiency and test
      the bio-safety and pump function of B4G12 cells with this model. METHODS: Thirty
      SD rats were divided into cryo-injury group and cryo-injury with B4G12 cell
      transplantation group. Models of corneal endothelium deficiency were created by
      cryo-injury with liquid nitrogen, and then B4G12 cells were transplanted into the
      eyes by anterior chamber injection. Corneas were checked under slit lamp and
      confocal microscope observations at some specific time points, pathological
      staining was also performed. RESULTS: The corneal endothelial cells were removed
      completely from the Descemet's membrane after cryo-injury. Cells transplanted
      firmly stuck to the Descemet's membrane. The corneas in the cryo-injury group
      were swelling with haze, while in the transplantation groups, the corneas
      restored transparence and normal thickness 2 weeks after the surgery. Confocal
      microscope and HE staining confirmed that in the cryo-injury group, the
      Descemet's membrane was denuded and the cornea stroma layer was in edema, on the
      contrary, in the other group, the transplanted cells completely covered the
      Descemet's membrane. CONCLUSION: Cryo-injury can be used for building the rat
      model of corneal endothelium deficiency, no neoplasm and inflammation reaction
      were found during the observation after B4G12 cells transplanted and B4G12 cells
      had the pump function in vivo.

PMID- 24931154
TI  - [Transplanted vascular endothelial cells to replace corneal endothelial cells by
      improved anterior chamber injection].
AB  - OBJECTIVE: To observe form and function changes of vascular endothelial cells
      (VEC) which were transplanted to the posterior surface of rhesus monkey cornea
      without Descemet's Membrane by anterior chamber injection, explore the
      feasibility of transplanting VEC to treat corneal endothelial injury, and find
      new method of corneal endothelial cell transplantation. METHODS: Cultured VEC to
      proliferate in vitro.Rhesus monkeys were randomly divided into two groups:
      Experimental group (6) and control group (6) according to a random number table.
      The experimental group:transplant the culured VEC to the posterior surface of
      rhesus monkey cornea without Descemet's membrane by anterior chamber injection.
      The control group:Tear out the Descemet's membrane by capsulotomy needle without
      VEC transplantation. A ultrasound apparatus was adopted to measure the
      postoperative thicknes of the cornea and Goldman intraocular pressure meter
      measuring intraocular pressure in the postoperative 7 days, 14 days, 30 days, 60
      days, 90 days, organize the data and entered into the computer , applicated the
      software of SPSS 11.5 for data independent samples t-test and analysis of
      variance. The eyes were removed respectively in postoperative 30, 60, 90 days to
      do pathological HE dyeing and scanning electron microscopy (SEM) observation of
      VEC in the posterior surface of cornea graft. RESULTS: Corneal transpareney:In
      the experimental observation period (3 months), the experimental group had better
      transparency than the control group with normal anterior chamber depth and
      without bullous keratopathy. And the corneal neovascularization was exist in the
      cornea graft in experimental group in the third month. After 3 months, the
      corneal thickness of experimental group (500 +/- 14) um was significantly lower
      than the control group (618 +/- 11) um, Corneal thickness values between
      experimental and control groups were statistically significant differences in
      changes (all P < 0.05, t-values were -3.256, -4.419, -12.896 postoperative 1, 2,
      3 months). Changes of intraocular pressure difference between the experimental
      group and the control was not statistically significant (all P > 0.05, t-values
      were -1.179, -2.166, -2.536 postoperative 1, 2, 3 months). The pathological:the
      cell layer was visible in the posterior surface of cornea graft. The control
      group:can't find the cell sample structure.SEM:Experimental group showed that VEC
      with irregular shape uniformly distributed on the inner surface of cornea and
      growing well, a small amount of white blood cells can be seen between VEC, and
      part of cellular debris exist in the trabecular meshwork. Control group showed a
      fiber material without VEC. CONCLUSIONS: Ultrasonic emulsification can
      established a repeatability and simple model of corneal endothelial injury in
      Rhesus monkeys.VEC can be transplanted to the corneal surface by Anterior chamber
      injection and the cells can grow on the surface and play a barrier role in
      maintaining the state of dehydration and transparency of the cornea to a certain
      extent. After transplantation, organizational structure and morphology of the
      anterior chamber angle does not produce pathological effects in the short term.
      Prompt that transplant the culured VEC to the posterior surface of rhesus monkey
      cornea without Descemet's Membrane by anterior chamber injection to substitute
      the function of the corneal endothelial cells may be a new idea for treatment of
      corneal endothelial damage.

PMID- 24931155
TI  - [Inhibited experimental mouse corneal neovascularization by CCR3 antagonist].
AB  - OBJECTIVE: To explore the effect of CCR3 antagonist on the development of
      experimental corneal neovascularization. METHODS: Mouse corneas were burned by
      NaOH to induce corneal neovascularization.Fifty four clean male BABL/c mice aged
      7-8 weeks were divided into control group, CCR3 antagonist group and VEGF
      antibody positive group according to randomized number table. The gene expression
      of CCR3 and its ligand eotaxin in burned corneas was examined by Real-time PCR.
      CCR3 antagonist was locally administrated after alkali injury and the formation
      of corneal neovascular 2 weeks after injury was examined using a digital camera
      linked to a slit lamp microscope and corneal whole mount staining with CD31. The
      mRNA and protein expression of chemokines in burned corneas was detected by Real
      time PCR and western blot. RESULTS: Compared to control group, CCR3 antagonist
      treated mice resulted in significantly decreased corneal neovascularization. The
      related CNV area was 0.51 +/- 0.03 in the CCR3 antagonist group, and that in the
      control group was 0.77 +/- 0.15, with significant difference between them (t =
      12.91, P = 0.00).Western blot detection did not show significant difference of
      VEGF protein expression between two groups.Expression level of VEGF in the CCR3
      antagonist group was 0.91 +/- 0.24, and that in the control group was 1.15 +/-
      0.30, showing no significant difference (t = 1.08, P = 0.34). CONCLUSIONS: Alkali
      induced corneal neovascularization was inhibited by CCR3 antagonist. The
      mechanism that CCR3 pathway plays an important role in corneal neovascularization
      needs further exploration.

PMID- 24931156
TI  - [Meibomian gland morphology study progression].
AB  - The meibomian gland (MG) in the eyelids, which is the largest sebaceous gland
      throughout the body, synthesize and secrete lipids to form the superficial tear
      film layer. It plays a key role in maintaining the ocular surface health.
      Abnormalities in meibomian gland morphology lead to meibomian gland dysfunction,
      which is the main cause of evaporative dry eye. Study on meibomian gland
      morphology will contribute significantly to the diagnosis and treatment of
      meibomian gland dysfunction. This review is just focusing on the current studies
      about techniques to visualize the morphology of the MG and changes of meibomian
      gland morphology related to diseases. 

PMID- 24931157
TI  - [Toxicity research status of benzalkonium chloride on ocular surface].
AB  - Benzalkonium chloride (BAC) is the most commonly used preservative in ophthalmic
      preparations.So far large bodies of clinical and experimental studies have shown
      that use of topical drugs containing BAC can induce a series of ocular surface
      diseases, such as apoptosis.However, recently, some clinical studies have shown
      that ocular toxicity in patients treated with eye drops containing BAC has not
      apparent correlated with BAC.Some scholars consider that the limitations of the
      research lead people to recognize the BAC toxicity exaggeratedly.Here we
      summarize numerous clinical and experimental studies of BAC in the past few
      years, and focus on reviewing recent researches of the toxic effect of BAC on
      ocular surface. 

PMID- 24931158
TI  - [The Boston keratoprosthesis].
AB  - The Boston Keratoprosthesis (KPro) is one of several types of artificial cornea
      manufactured worldwide that are being implanted in increasing numbers in patients
      with severe corneal diseases and graft failures. To summerize the advances in
      design of the Boston type I keratoprosthesis and in the treatment strategies to
      conquer the post operative complications have expanded the indications and
      application of this technology. Many modifications to the design of the Boston
      type I keratoprosthesis and treatment of the patient in the post operative period
      have occurred. Also, the technology has been more widely accepted as a primary
      surgical option for patients with a poor preoperative prognosis for traditional
      penetrating keratoplasty. The outcomes of visual acuity, retention, and post
      operative infection rates have all significantly improved since the technology
      has been modified and offers patients an alternative for visual rehabilitation.
      This is implanted into a carrier corneal graft or into the patient's own cornea.
      The allograft cornea can be the carrier, which may solve the shortage of donor
      cornea in China. 

PMID- 24931159
TI  - All models are wrong.
AB  - As the field of phylogeography has continued to move in the model-based
      direction, researchers continue struggling to construct useful models for
      inference. These models must be both simple enough to be tractable yet contain
      enough of the complexity of the natural world to make meaningful inference.
      Beyond constructing such models for inference, researchers explore model space
      and test competing models with the data on hand, with the goal of improving the
      understanding of the natural world and the processes underlying natural
      biological communities. Approximate Bayesian computation (ABC) has increased in
      recent popularity as a tool for evaluating alternative historical demographic
      models given population genetic samples. As a thorough demonstration, Pelletier &
      Carstens (2014) use ABC to test 143 phylogeographic submodels given
      geographically widespread genetic samples from the salamander species Plethodon
      idahoensis (Carstens et al. 2014) and, in so doing, demonstrate how the results
      of the ABC model choice procedure are dependent on the model set one chooses to
      evaluate.

PMID- 24931160
TI  - MiR-146b is a regulator of human visceral preadipocyte proliferation and
      differentiation and its expression is altered in human obesity.
AB  - Visceral obesity is an independent risk factor for metabolic syndrome, and
      abnormal fat accumulation is linked to increases in the number and size of
      adipocytes. MiR-146b was a miRNA highly expressed in mature adipocytes while very
      lowly expressed in human mesenchymal stem cells (hMSCs) and human visceral
      preadipocytes (vHPA). In this paper, we mainly focused on the roles of miR-146b
      in adipogenesis. We found miR-146b could inhibit the proliferation of visceral
      preadipocytes and promote their differentiation. MiR-146b in human visceral
      adipocytes inhibited the expression of KLF7, a member of the Kruppel-like
      transcription factors, as demonstrated by a firefly luciferase reporter assay,
      indicating that KLF7 is a direct target of the endogenous miR-146b. MiR-146b
      expression was significantly altered in visceral and subcutaneous adipose tissues
      in human overweight and obese subjects, and in the epididymal fat tissues and
      brown fat tissues of diet-induced obese mice. Our data indicates that miR-146b
      may be a new therapeutic target against human visceral obesity and metabolic
      dysfunction.

PMID- 24931161
TI  - CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity
      in medullary thyroid cancer in vitro and in vivo.
AB  - CLM29 (a pyrazolo[3,4-d]pyrimidine, that inhibits RET, epidermal growth factor
      receptor, vascular endothelial growth factor receptor, and has an anti-angiogenic
      activity) has anti-neoplastic activity in papillary dedifferentiated thyroid
      cancer. Here we tested CLM29 in medullary thyroid cancer (MTC), in primary MTC
      cells (P-MTC) obtained at surgery, and in TT cells harboring (C634W) RET
      mutation. CLM29 (10, 30, 50 MUM) inhibited significantly (P<0.001) the
      proliferation, and increased the percentage of apoptotic P-MTC, TT and human
      dermal microvascular endothelial cells. The inhibition of proliferation by CLM29
      was similar in P-MTC cells with/without RET mutation. TT cells were injected sc
      in CD nu/nu mice, and tumor masses became detectable between 20 and 30 days after
      xenotransplantation; CLM29 (50mg/kg/die) reduced significantly tumor growth and
      weight, and microvessel density. The anti-tumor activity of CLM29 has been shown
      in MTC in vitro, and in vivo, opening the way to a future clinical evaluation.

PMID- 24931162
TI  - Tyrosine phosphatase SHP2 increases cell motility in triple-negative breast
      cancer through the activation of SRC-family kinases.
AB  - Tumor cell migration has a fundamental role in early steps of metastasis, the
      fatal hallmark of cancer. In the present study, we investigated the effects of
      the tyrosine phosphatase, SRC-homology 2 domain-containing phosphatase 2 (SHP2),
      on cell migration in metastatic triple-negative breast cancer (TNBC), an
      aggressive disease associated with a poor prognosis for which a targeted therapy
      is not yet available. Using mouse models and multiphoton intravital imaging, we
      have identified a crucial effect of SHP2 on TNBC cell motility in vivo. Further,
      analysis of TNBC cells revealed that SHP2 also influences cell migration,
      chemotaxis and invasion in vitro. Unbiased phosphoproteomics and biochemical
      analysis showed that SHP2 activates several SRC-family kinases and downstream
      targets, most of which are inducers of migration and invasion. In particular,
      direct interaction between SHP2 and c-SRC was revealed by a fluorescence
      resonance energy transfer assay. These results suggest that SHP2 is a crucial
      factor during early steps of TNBC migration to distant organs. 

PMID- 24931165
TI  - Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1
      promotes cancer cell proliferation and invasion independent of its enzymatic
      activity.
AB  - Heme oxygenase-1 (HO-1) is a heme-degrading enzyme anchored in the endoplasmic
      reticulum by a carboxyl-terminal transmembrane segment (TMS). HO-1 is highly
      expressed in various cancers and its nuclear localization is associated with the
      progression of some cancers. Nevertheless, the mechanism underlying HO-1 nuclear
      translocation and its pathological significance remain elusive. Here we show that
      the signal peptide peptidase (SPP) catalyzes the intramembrane cleavage of HO-1.
      Coexpression of HO-1 with wild-type SPP, but not a dominant-negative SPP,
      promoted the nuclear localization of HO-1 in cells. Mass spectrometry analysis of
      cytosolic HO-1 isolated from HeLa cells overexpressing HO-1 and SPP revealed two
      adjacent intramembrane cleavage sites located after S275 and F276 within the TMS.
      Mutations of S275F276 to A275L276 significantly hindered SPP-mediated HO-1
      cleavage and nuclear localization. Nuclear HO-1 was detected in A549 and DU145
      cancer cell lines expressing high levels of endogenous HO-1 and SPP. SPP
      knockdown or inhibition significantly reduced nuclear HO-1 localization in A549
      and DU145 cells. The positive nuclear HO-1 stain was also evident in lung cancer
      tissues expressing high levels of HO-1 and SPP. Overexpression of a truncated HO
      1 (t-HO-1) lacking the TMS in HeLa and H1299 cells promoted cell proliferation
      and migration/invasion. The effect of t-HO-1 was not affected by a mutation in
      the catalytic site. However, blockade of t-HO-1 nuclear localization abolished t
      HO-1-mediated effect. The tumorigenic effect of t-HO-1 was also demonstrated in
      the mouse model. These findings disclose that SPP-mediated intramembrane cleavage
      of HO-1 promotes HO-1 nuclear localization and cancer progression independent of
      HO-1 enzymatic activity.

PMID- 24931163
TI  - mTORC1 drives HIF-1alpha and VEGF-A signalling via multiple mechanisms involving
      4E-BP1, S6K1 and STAT3.
AB  - Recent clinical trials using rapalogues in tuberous sclerosis complex show
      regression in volume of typically vascularised tumours including angiomyolipomas
      and subependymal giant cell astrocytomas. By blocking mechanistic/mammalian
      target of rapamycin complex 1 (mTORC1) signalling, rapalogue efficacy is likely
      to occur, in part, through suppression of hypoxia-inducible factors (HIFs) and
      vascular endothelial growth factors (VEGFs). We show that rapamycin reduces HIF
      1alpha protein levels, and to a lesser extent VEGF-A levels, in renal cystadenoma
      cells in a Tsc2+/- mouse model. We established that mTORC1 drives HIF-1alpha
      protein accumulation through enhanced transcription of HIF-1alpha mRNA, a process
      that is blocked by either inhibition or knockdown of signal transducer and
      activation of transcription 3 (STAT3). Furthermore, we demonstrated that STAT3 is
      directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1alpha
      mRNA transcription. mTORC1 also regulates HIF-1alpha synthesis on a translational
      level via co-operative regulation of both initiation factor 4E-binding protein 1
      (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas HIF-1alpha degradation
      remains unaffected. We therefore proposed that mTORC1 drives HIF-1alpha synthesis
      in a multifaceted manner through 4E-BP1/eIF4E, S6K1 and STAT3. Interestingly, we
      observed a disconnect between HIF-1alpha protein levels and VEGF-A expression.
      Although both S6K1 and 4E-BP1 regulate HIF-1alpha translation, VEGF-A is
      primarily under the control of 4E-BP1/eIF4E. S6K1 inhibition reduces HIF-1alpha
      but not VEGF-A expression, suggesting that mTORC1 mediates VEGF-A expression via
      both HIF-1alpha-dependent and -independent mechanisms. Our work has important
      implications for the treatment of vascularised tumours, where mTORC1 acts as a
      central mediator of STAT3, HIF-1alpha, VEGF-A and angiogenesis via multiple
      signalling mechanisms.

PMID- 24931164
TI  - RECK controls breast cancer metastasis by modulating a convergent, STAT3
      dependent neoangiogenic switch.
AB  - Metastasis is the primary cause of cancer-related death in oncology patients. A
      comprehensive understanding of the molecular mechanisms that cancer cells usurp
      to promote metastatic dissemination is critical for the development and
      implementation of novel diagnostic and treatment strategies. Here we show that
      the membrane protein RECK (Reversion-inducing cysteine-rich protein with kazal
      motifs) controls breast cancer metastasis by modulating a novel, non-canonical
      and convergent signal transducer and activator of transcription factor 3 (STAT3)
      dependent angiogenic program. Neoangiogenesis and STAT3 hyperactivation are known
      to be fundamentally important for metastasis, but the root molecular initiators
      of these phenotypes are poorly understood. Our study identifies loss of RECK as a
      critical and previously unknown trigger for these hallmarks of metastasis. Using
      multiple xenograft mouse models, we comprehensively show that RECK inhibits
      metastasis, concomitant with a suppression of neoangiogenesis at secondary sites,
      while leaving primary tumor growth unaffected. Further, with functional genomics
      and biochemical dissection we demonstrate that RECK controls this angiogenic
      rheostat through a novel complex with cell surface receptors to regulate STAT3
      activation, cytokine signaling, and the induction of both vascular endothelial
      growth factor and urokinase plasminogen activator. In accordance with these
      findings, inhibition of STAT3 can rescue this phenotype both in vitro and in
      vivo. Taken together, our study uncovers, for the first time, that RECK is a
      novel regulator of multiple well-established and robust mediators of metastasis;
      thus, RECK is a keystone protein that may be exploited in a clinical setting to
      target metastatic disease from multiple angles. 

PMID- 24931166
TI  - Antisense transcription at the TRPM2 locus as a novel prognostic marker and
      therapeutic target in prostate cancer.
AB  - Overwhelming evidence indicates that cancer is a genetic disease caused by the
      accumulation of mutations in oncogenes and tumor suppressor genes. It is also
      increasingly apparent, however, that cancer depends not only on mutations in
      these coding genes but also on alterations in the large class of non-coding RNAs.
      Here, we report that one such long non-coding RNA, TRPM2-AS, an antisense
      transcript of TRPM2, which encodes an oxidative stress-activated ion channel, is
      overexpressed in prostate cancer (PCa). The high expression of TRPM2-AS and its
      related gene signature were found to be linked to poor clinical outcome, with the
      related gene signature working also independently of the patient's Gleason score.
      Mechanistically, TRPM2-AS knockdown led to PCa cell apoptosis, with a
      transcriptional profile that indicated an unbearable increase in cellular stress
      in the dying cells, which was coupled to cell cycle arrest, an increase in
      intracellular hydrogen peroxide and activation of the sense TRPM2 gene. Moreover,
      targets of existing drugs and treatments were found to be consistently associated
      with high TRPM2-AS levels in both targeted cells and patients, ultimately
      suggesting that the measurement of the expression levels of TRPM2-AS allows not
      only for the early identification of aggressive PCa tumors, but also identifies a
      subset of at-risk patients who would benefit from currently available, but mostly
      differently purposed, therapeutic agents.

PMID- 24931167
TI  - An intergenic regulatory region mediates Drosophila Myc-induced apoptosis and
      blocks tissue hyperplasia.
AB  - Induction of cell-autonomous apoptosis following oncogene-induced
      overproliferation is a major tumor-suppressive mechanism in vertebrates. However,
      the detailed mechanism mediating this process remains enigmatic. In this study,
      we demonstrate that dMyc-induced cell-autonomous apoptosis in the fruit fly
      Drosophila melanogaster relies on an intergenic sequence termed the IRER
      (irradiation-responsive enhancer region). The IRER mediates the expression of
      surrounding proapoptotic genes, and we use an in vivo reporter of the IRER
      chromatin state to gather evidence that epigenetic control of DNA accessibility
      within the IRER is an important determinant of the strength of this response to
      excess dMyc. In a previous work, we showed that the IRER also mediates P53
      dependent induction of proapoptotic genes following DNA damage, and the chromatin
      conformation within IRER is regulated by polycomb group-mediated histone
      modifications. dMyc-induced apoptosis and the P53-mediated DNA damage response
      thus overlap in a requirement for the IRER. The epigenetic mechanisms controlling
      IRER accessibility appear to set thresholds for the P53- and dMyc-induced
      expression of apoptotic genes in vivo and may have a profound impact on cellular
      sensitivity to oncogene-induced stress.

PMID- 24931170
TI  - Targeting WNT1-inducible signaling pathway protein 2 alters human breast cancer
      cell susceptibility to specific lysis through regulation of KLF-4 and miR-7
      expression.
AB  - The molecular basis for the resistance of tumor cells to cell-mediated
      cytotoxicity remains poorly understood and thus poses a major challenge for
      cancer immunotherapy. The present study was designed to determine whether the
      WNT1-inducible signaling pathway protein 2 (WISP2, also referred to as CCN5), a
      key regulator of tumor cell plasticity, interferes with tumor susceptibility to
      cytotoxic T-lymphocyte (CTL)-mediated lysis. We found that silencing WISP2
      signaling in human breast adenocarcinoma MCF7 cells impairs CTL-mediated cell
      killing by a mechanism involving stem cell marker Kruppel-like factor-4 (KLF-4)
      induction and microRNA-7 (miR-7) downregulation. Inhibition of transforming
      growth factor beta (TGF-beta) signaling using the A83-01 inhibitor in MCF7
      shWISP2 cells resulted in a significant reversal of the epithelial-to-mesenchymal
      transitioned (EMT) phenotype, the expression of KLF-4 and a partial recovery of
      target susceptibility to CTLs. More importantly, we showed that silencing KLF-4
      was accompanied by a reduction in MCF7-shWISP2 resistance to CTLs. Using human
      breast cancer tissues, we demonstrated the coexpression of KLF-4 with EMT markers
      and TGF-beta pathway signaling components. More importantly, we found that KLF-4
      expression was accompanied by miR-7 inhibition, which is partly responsible for
      impairing CTL-mediated lysis. Thus, our data indicate that WISP2 has a role in
      regulating tumor cell susceptibility through EMT by inducing the TGF-beta
      signaling pathway, KLF-4 expression and miR-7 inhibition. These studies indicate
      for the first time that WISP2 acts as an activator of CTL-induced killing and
      suggests that the loss of its function promotes evasion of immunosurveillance and
      the ensuing progression of the tumor. 

PMID- 24931169
TI  - Cellular senescence checkpoint function determines differential Notch1-dependent
      oncogenic and tumor-suppressor activities.
AB  - Notch activity regulates tumor biology in a context-dependent and complex manner.
      Notch may act as an oncogene or a tumor-suppressor gene even within the same
      tumor type. Recently, Notch signaling has been implicated in cellular senescence.
      Yet, it remains unclear as to how cellular senescence checkpoint functions may
      interact with Notch-mediated oncogenic and tumor-suppressor activities. Herein,
      we used genetically engineered human esophageal keratinocytes and esophageal
      squamous cell carcinoma cells to delineate the functional consequences of Notch
      activation and inhibition along with pharmacological intervention and RNA
      interference experiments. When expressed in a tetracycline-inducible manner, the
      ectopically expressed activated form of Notch1 (ICN1) displayed oncogene-like
      characteristics inducing cellular senescence corroborated by the induction of
      G0/G1 cell-cycle arrest, Rb dephosphorylation, flat and enlarged cell morphology
      and senescence-associated beta-galactosidase activity. Notch-induced senescence
      involves canonical CSL/RBPJ-dependent transcriptional activity and the p16(INK4A)
      Rb pathway. Loss of p16(INK4A) or the presence of human papilloma virus (HPV)
      E6/E7 oncogene products not only prevented ICN1 from inducing senescence but
      permitted ICN1 to facilitate anchorage-independent colony formation and xenograft
      tumor growth with increased cell proliferation and reduced squamous-cell
      differentiation. Moreover, Notch1 appears to mediate replicative senescence as
      well as transforming growth factor-beta-induced cellular senescence in non
      transformed cells and that HPV E6/E7 targets Notch1 for inactivation to prevent
      senescence, revealing a tumor-suppressor attribute of endogenous Notch1. In
      aggregate, cellular senescence checkpoint functions may influence dichotomous
      Notch activities in the neoplastic context.

PMID- 24931168
TI  - Epigenetic mechanisms of tumorigenicity manifesting in stem cells.
AB  - One of the biggest roadblocks to using stem cells as the basis for regenerative
      medicine therapies is the tumorigenicity of stem cells. Unfortunately, the unique
      abilities of stem cells to self-renew and differentiate into a variety of cell
      types are also mechanistically linked to their tumorigenic behaviors.
      Understanding the mechanisms underlying the close relationship between stem cells
      and cancer cells has therefore become a primary goal in the field. In addition,
      knowledge gained from investigating the striking parallels between mechanisms
      orchestrating normal embryogenesis and those that invoke tumorigenesis may well
      serve as the foundation for developing novel cancer treatments. Emerging
      discoveries have demonstrated that epigenetic regulatory machinery has important
      roles in normal stem cell functions, cancer development and cancer stem cell
      (CSC) identity. These studies provide valuable insights into both the shared and
      distinct mechanisms by which pluripotency and oncogenicity are established and
      regulated. In this review, the cancer-related epigenetic mechanisms found in
      pluripotent stem cells and cancer cells will be discussed, focusing on both the
      similarities and the differences.

PMID- 24931171
TI  - Bortezomib use in a pediatric cardiac transplant center.
AB  - Data are limited on the efficacy and safety of bortezomib for the treatment of
      AMR following OHT for pediatric acquired or CHD. Retrospective chart review
      identified patients who received bortezomib for acute (n = 3, within two wk of
      diagnosis) and chronic (n = 1, three months after diagnosis) AMR or as part of a
      desensitization regimen (n = 1). Bortezomib was associated with a 3-66% reduction
      in class I DSA and a 7-82% reduction in class II DSA. Two of the three acute AMR
      cases resolved by the first follow-up biopsy. Two patients with AMR resolution
      are currently well. One patient developed a second episode of AMR, which was
      unresponsive to bortezomib therapy and required retransplantation for progressive
      coronary allograft vasculopathy. One patient died shortly after the third cycle
      from multi-organ failure. The desensitization patient showed transient HLA
      reduction with two cycles, but died five months after transplant from sepsis.
      Complications included infection (3/5), peripheral neuropathy (2/5), AKI (2/5),
      and thrombocytopenia (3/5). Adverse events appear more common in critically ill
      patients. Bortezomib therapy resulted in variable DSA reduction and AMR
      resolution in AMR in OHT secondary to pediatric acquired or CHD. 

PMID- 24931172
TI  - Downregulation of lipogenesis and fatty acid oxidation in the subcutaneous
      adipose tissue of morbidly obese women.
AB  - OBJECTIVE: The aim of this study was to analyse the expression of crucial genes
      in fatty acid metabolism in visceral (VAT) and subcutaneous (SAT) adipose tissue
      samples from morbidly obese women. METHODS: The VAT and SAT expression of key
      genes in 145 morbidly obese women (MO, BMI > 40 Kg/m(2) ) and 18 normal weight
      control women by RT-PCR and Western Blot was analyzed. RESULTS: In SAT, the
      expression levels of the genes related to lipogenesis and fatty acid oxidation
      were significantly lower in MO than in controls. In VAT, most of the lipogenic
      genes studied had similar expression levels in MO and control cohort. Regarding
      inflammation, IL6 was significantly higher in MO in both tissues whereas TNFalpha
      mRNA expression was significantly higher only in VAT. CONCLUSIONS: Our results
      indicate that in morbidly obese patients, lipogenesis and fatty acid oxidation
      are downregulated in SAT, whereas in VAT these pathways are almost unchanged. By
      contrast, inflammation is induced in both adipose tissues. It is hypothesized
      that, in this type of extreme obesity, SAT works to limit any further development
      of fat mass, decreasing the expression of lipogenic and FA oxidative genes
      whereas VAT depot might have lost this capability.

PMID- 24931173
TI  - Persistent left and absent right superior vena cava: combined functional and
      anatomic assessment with transthoracic echocardiography and computed tomography.

PMID- 24931176
TI  - Low cost lab-on-a-chip prototyping with a consumer grade 3D printer.
AB  - Versatile prototyping of 3D printed lab-on-a-chip devices, supporting different
      forms of sample delivery, transport, functionalization and readout, is
      demonstrated with a consumer grade printer, which centralizes all critical
      fabrication tasks. Devices cost 0.57US$ and are demonstrated in chemical sensing
      and micromixing examples, which exploit established principles from reference
      technologies. 

PMID- 24931175
TI  - Single-molecule mechanochemical sensing using DNA origami nanostructures.
AB  - While single-molecule sensing offers the ultimate detection limit, its throughput
      is often restricted as sensing events are carried out one at a time in most
      cases. 2D and 3D DNA origami nanostructures are used as expanded single-molecule
      platforms in a new mechanochemical sensing strategy. As a proof of concept, six
      sensing probes are incorporated in a 7-tile DNA origami nanoassembly, wherein
      binding of a target molecule to any of these probes leads to mechanochemical
      rearrangement of the origami nanostructure, which is monitored in real time by
      optical tweezers. Using these platforms, 10 pM platelet-derived growth factor
      (PDGF) are detected within 10 minutes, while demonstrating multiplex sensing of
      the PDGF and a target DNA in the same solution. By tapping into the rapid
      development of versatile DNA origami nanostructures, this mechanochemical
      platform is anticipated to offer a long sought solution for single-molecule
      sensing with improved throughput. 

PMID- 24931174
TI  - Behavioural screening of zebrafish using neuroactive traditional Chinese medicine
      prescriptions and biological targets.
AB  - The mechanism of the therapeutic action of antidepressants remains uncertain in
      traditional Chinese medicine (TCM). In this study, we selected 7 classical TCM
      prescriptions and utilised an automatic video-tracking system to monitor the
      rest/wake behaviour of larval zebrafish at 4 days post-fertilisation (dpf) for 48
      hours. We found that the curative effects of the prescriptions were dose
      dependent. K-means clustering was performed according to the shared behavioural
      phenotypes of the zebrafish. The results revealed that the rest/wake behavioural
      profiles induced by the same class of prescriptions were similar. A correlation
      analysis was conducted between the TCM prescriptions and the known compounds. The
      results showed that the TCM prescriptions correlated well with some well-known
      compounds. Therefore, we predicted that they may share a similar mechanism of
      action. This paper describes the first study to combine TCM research with
      zebrafish rest/wake behaviour in vivo and presents a powerful approach for the
      discovery of the mechanism of action of TCM prescriptions. 

PMID- 24931177
TI  - Femoral approach: an exceptional alternative for permanent pacemaker
      implantation.
AB  - The classic transvenous implantation of a permanent pacemaker in a pectoral
      location may be precluded by obstruction of venous access through the superior
      vena cava or recent infection at the implant site. When these barriers to the
      procedure are bilateral and there are also contraindications or technical
      difficulties to performing a thoracotomy for an epicardial approach, the femoral
      vein, although rarely used, can be a viable alternative. We describe the case of
      a patient with occlusion of both subclavian veins and a high risk for mini
      thoracotomy or videothoracoscopy, who underwent implantation of a permanent
      single-chamber pacemaker via the right femoral vein. 

PMID- 24931178
TI  - An asymptomatic case of a giant left atrium.

PMID- 24931179
TI  - Epicardial ablation for prevention of ventricular fibrillation in a patient with
      Brugada syndrome.
AB  - We present the case of a 60-year-old woman with Brugada syndrome, permanent type
      1 electrocardiographic pattern, who had previously received an implantable
      cardioverter-defibrillator. She suffered frequent syncopal episodes and multiple
      appropriate shocks (around five per month) due to polymorphic ventricular
      tachycardia/ventricular fibrillation, refractory to quinidine therapy. Combined
      epicardial and endocardial electroanatomical mapping was performed with a view to
      substrate ablation. An area of abnormal fractionated electrograms, lasting up to
      370 ms and up to 216 ms after the end of the surface QRS, was identified in the
      epicardium in the lower anterior part of the right ventricular outflow tract.
      Extensive epicardial ablation of this area, which eliminated the fractionated
      electrograms, led to the disappearance of the Brugada electrocardiographic
      pattern six weeks after ablation. Despite discontinuation of quinidine, no
      further ventricular arrhythmias occurred during follow-up, which is still of
      short duration. 

PMID- 24931180
TI  - The proarrhythmic effect of cardiac resynchronization therapy: an issue that
      should be borne in mind.
AB  - The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing
      mortality and hospitalizations for heart failure, improving NYHA functional class
      and inducing reverse remodeling have led to its increasing use in clinical
      practice. However, its potential contribution to complex ventricular arrhythmias
      is controversial.We present the case of a female patient with valvular heart
      failure and severe systolic dysfunction, in NYHA class III and under optimal
      medical therapy, without previous documented ventricular arrhythmias. After
      implantation of a CRT defibrillator, she suffered an arrhythmic storm with
      multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12
      shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as
      reproducible VT runs induced by biventricular pacing. Since no other vein of the
      coronary sinus system was accessible, it was decided to implant an epicardial
      lead to stimulate the left ventricle, positioned in the left ventricular mid
      lateral wall. No arrhythmias were detected in the following six months. This case
      highlights the possible proarrhythmic effect of biventricular pacing with a left
      ventricular lead positioned in the coronary sinus venous system. 

PMID- 24931181
TI  - Post-cardiac injury syndrome following transvenous pacing: case report.
AB  - Post-cardiac injury syndrome (PCIS) is an inflammatory process involving the
      pericardium secondary to cardiac injury. It can develop after cardiac trauma,
      cardiac surgery, myocardial infarction, and, rarely, after certain intravascular
      procedures. We report a rare case of an iatrogenic cardiac rupture followed by
      PCIS with delayed inflammatory pericardial effusion after pacemaker implantation.
      A comprehensive literature review on this topic is provided. 

PMID- 24931182
TI  - New-onset atrial fibrillation during acute coronary syndromes: predictors and
      prognosis.
AB  - INTRODUCTION: New-onset atrial fibrillation (AF) frequently complicates
      myocardial infarction, with an incidence of 6-21%. OBJECTIVE: To assess the
      predictors and prognosis of new-onset AF during acute coronary syndromes (ACS).
      METHODS: We performed a retrospective observational cohort study including 902
      consecutive patients (mean age 64 years, 77.5% male) admitted to a single center
      over a two-year period, with a six-month follow-up. RESULTS: AF rhythm was
      identified in 13.8% patients, of whom 73.3% presented new-onset AF and 26.8% pre
      existing AF. New-onset AF was more frequent in older (p<0.001) and hypertensive
      patients (p=0.001) and in those with previous valvular heart disease (p<0.001)
      and coronary artery bypass grafting (p=0.049). During hospitalization, patients
      with new-onset AF more often had respiratory infection (p=0.002) and heart
      failure (p<0.001), and higher values of NT-proBNP (p=0.007) and peak creatinine
      (p=0.001). On echocardiography they had greater left atrial (LA) diameter
      (p<0.001) and more frequent significant mitral regurgitation (p<0.001) and left
      ventricular ejection fraction (LVEF) <=40% (p<0.001) and were less likely to have
      significant coronary lesions (p=0.009) or to have undergone coronary
      revascularization (p<0.001). In multivariate analysis, age (OR 1.06, p=0.021),
      LVEF <=40% (OR 4.91, p=0.002) and LA diameter (OR 1.14, p=0.008) remained
      independent predictors of new-onset AF. Together with age, diabetes and maximum
      Killip class, this arrhythmia was an independent predictor of overall mortality
      (OR 3.11, p=0.032). CONCLUSIONS: Age, LVEF <=40% and LA diameter are independent
      predictors of new-onset AF during ACS. This arrhythmia is associated with higher
      overall mortality (in-hospital and in follow-up).

PMID- 24931183
TI  - Formulation of sage essential oil (Salvia officinalis, L.) monoterpenes into
      chitosan hydrogels and permeation study with GC-MS analysis.
AB  - This study deals with the formulation of natural drugs into hydrogels. For the
      first time, compounds from the sage essential oil were formulated into chitosan
      hydrogels. A sample preparation procedure for hydrophobic volatile analytes
      present in a hydrophilic water matrix along with an analytical method based on
      the gas chromatography coupled with the mass spectrometry (GC-MS) was developed
      and applied for the evaluation of the identity and quantity of essential oil
      components in the hydrogels and saline samples. The experimental results revealed
      that the chitosan hydrogels are suitable for the formulation of sage essential
      oil. The monoterpene release can be effectively controlled by both chitosan and
      caffeine concentration in the hydrogels. Permeation experiment, based on a
      hydrogel with the optimized composition [3.5% (w/w) sage essential oil, 2.0%
      (w/w) caffeine, 2.5% (w/w) chitosan and 0.1% (w/w) Tween-80] in donor
      compartment, saline solution in acceptor compartment, and semi-permeable
      cellophane membrane, demonstrated the useful permeation selectivity. Here,
      (according to lipophilicity) an enhanced permeation of the bicyclic monoterpenes
      with antiflogistic and antiseptic properties (eucalyptol, camphor and borneol)
      and, at the same time, suppressed permeation of toxic thujone (not exceeding its
      permitted applicable concentration) was observed. These properties highlight the
      pharmaceutical importance of the developed chitosan hydrogel formulating sage
      essential oil in the dermal applications. 

PMID- 24931184
TI  - [Hepatitis B and C among volunteer non-remunerated blood donors in Eastern
      Democratic Republic of Congo].
AB  - OBJECTIVE: We aimed to evaluate the global prevalence of hepatitis B and C among
      voluntary blood donor. METHODS: In the study, 1079 blood donors were included.
      The investigation was carried out from 1 January till 31 December 2010 in the
      central Blood Bank of Bukavu in DRC. The median age of sample was 26 years. In
      total, 72.4% among them were male sex and 54.5% of new blood donors. RESULTS: The
      prevalence of hepatitis B was 4.2% and hepatitis C was found in 3.8% case the
      coinfection VHB and VHC with 2.2%. VHB was prevalent in blood donor group of less
      than 30 years (5.0%), new blood donor (5.1%), in medical profession (7.1%) and in
      the male sex group (5.1%) and was significantly according to the sex (P=0.01) and
      the place of residence (P=0.002). A strong association was showed between the
      rural medium and hepatitis B OR 3,1 (1.4-6.5) and VHC OR 2.9 (1.3-6.5). After
      estimation with logistic regression a higher risk of seropositivity of VHB found
      in blood donor sex male group, married group, blood donor coming from the rural
      middle and having less than 30 years. CONCLUSION: For blood safety, a particular
      attention must be laid in the selection of donor before a blood donation and in
      donation in reagent.

PMID- 24931185
TI  - Azithromycin improves lung function in patients with post-lung transplant
      bronchiolitis obliterans syndrome: a meta-analysis.
AB  - INTRODUCTION: Azithromycin has been shown to reverse or halt the decline of
      forced expiratory volume in one s (FEV1) in patients with bronchiolitis
      obliterans (BOS) syndrome following lung transplant. The overall effect of
      azithromycin on the absolute values of FEV1 has not been compared between
      reported studies. We studied the effects of azithromycin on lung function in
      patients with post-lung transplant BOS syndrome. METHODS: A meta-analysis was
      performed using studies identified following an extensive database search. To be
      included, studies were published in English or French and explicitly reported
      percentage change in FEV1 or hazard ratios. RESULTS: A total of 10 studies were
      included in this review. One hundred and forty patients were evaluated after
      treatment with azithromycin for an average follow-up period of seven months. The
      mean percentage increase in FEV1 was 8.8 (CI 5.1-12.47) p < 0.001. The pooled
      hazard ratio was 0.25 (CI 0.06-0.56) p = 0.041 for a mean follow-up period of 2.9
      yr. CONCLUSION: This study demonstrated a significant improvement in lung
      function in patients with BOS syndrome following lung transplant after seven
      months of treatment. It remains uncertain whether this improvement stays after
      seven months. We also found that patients on azithromycin were less likely to die
      from BOS syndrome compared with patients who were not on azithromycin.

PMID- 24931186
TI  - Negative Symptoms in Schizophrenia: Where We have been and Where We are Heading.
AB  - This review traces the history of negative symptom profiles in neuropsychiatry
      from their earliest emergence in the 19th century to the current psychiatric
      concepts and therapeutic approaches. Recent investigations performing exploratory
      and confirmatory factor analysis have suggested that negative symptoms are
      multidimensional, including evidence for at least two distinct negative symptom
      subdomains: diminished expression and amotivation. Preliminary studies have
      demonstrated the clinical validity of this distinction. Several potential
      pathophysiological validating factors based on brain imaging analysis of
      emotional experiences and expressions in individuals with schizophrenia are
      examined. Finally, the potential of different treatment strategies, including
      medications and various psychotherapeutic techniques, to most favorably treat
      each of these subdomains is discussed. 

PMID- 24931187
TI  - Spontaneously resolving granulomatous tattoo reaction in multiple color regions.

PMID- 24931188
TI  - Generation of 1:1 Carbamazepine:Nicotinamide cocrystals by spray drying.
AB  - The present study investigates the potential of spray drying as a technique for
      generation of pharmaceutical cocrystals. Carbamazepine-Nicotinamide cocrystal
      (CNC) was chosen as model cocrystal system for this study. Firstly, CNC was
      generated using liquid assisted grinding and used for generation of phase
      solubility diagram (PSD) and ternary phase diagram (TPD). Both PSD and TPD were
      carefully evaluated for phase behavior of CNC when equilibrated with solvent. The
      undersaturated region with respect to CNC, as depicted by TPD, was selected as
      target region to initiate cocrystallization experiments. Various points in this
      region, representative of different compositions of Carbamazepine, Nicotinamide
      and CNC, were selected and spray drying was carried out. The spray dried product
      was characterized for solid state properties and was compared with CNC generated
      by liquid assisted grinding. Spray drying successfully generated CNC of similar
      quality as those generated by liquid assisted grinding. Moreover, there was no
      significant impact of process variables on formation of CNC. Spray drying, owing
      to its simplicity and industrial scalability, can be a promising method for large
      scale cocrystal generation. 

PMID- 24931189
TI  - Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive
      targeted drug delivery.
AB  - Targeted drug delivery is a promising alternative to overcome the limitations of
      classical chemotherapy. In an ideal targeted drug delivery system carrier
      nanoparticles would be directed to the tumor tissue and selectively release
      therapeutic molecules. As a novel approach, chitosan coated magnetic
      nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides
      targeting of drugs to the tumor site under a magnetic field. Among various
      materials, chitosan has a great importance as a pH sensitive, natural,
      biodegradable, biocompatible and bioadhesive polymer. The aim of this study was
      to obtain an effective targeted delivery system for Doxorubicin, using chitosan
      coated MNPs. Different sized CS MNPs were produced by in situ synthesis method.
      The anti-cancer agent Doxorubicin was loaded onto CS MNPs which were
      characterized previously. Doxorubicin loading was confirmed by FTIR. Drug loading
      and release characteristics, and stability of the nanoparticles were
      investigated. Our results showed that the CS MNPs have pH responsive release
      characteristics. The cellular internalization of Doxorubicin loaded CS MNPs were
      visualized by fluorescent microscopy. Doxorubicin loaded CS MNPs are efficiently
      taken up by MCF-7 (MCF-7/S) and Doxorubicin resistant MCF-7 (MCF-7/1 MUM) breast
      cancer cells, which increases the efficacy of drug and also maintains overcoming
      the resistance of Doxorubicin in MCF-7/Dox cells. Consequently, CS MNPs
      synthesized at various sizes can be effectively used for the pH dependent release
      of Doxorubicin in cancer cells. Results of this study can provide new insights in
      the development of pH responsive targeted drug delivery systems to overcome the
      side effects of conventional chemotherapy.

PMID- 24931190
TI  - Sustained release of PTX-incorporated nanoparticles synergized by burst release
      of DOX?HCl from thermosensitive modified PEG/PCL hydrogel to improve anti-tumor
      efficiency.
AB  - As drug therapies become increasingly sophisticated, the synergistic benefits of
      two or more drugs are often required. In this study, we aimed at improving anti
      tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable
      hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX?HCl).
      Thermosensitive injectable hydrogel composed of nanoparticles assembled from
      amphiphilic copolymer poly(epsilon-caprolactone-co-1,4,8-trioxa[4.6]spiro-9
      undecanone)-poly(ethylene glycol)-poly(epsilon-caprolaone-co-1,4,8
      trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and
      hydrophilic DOX?HCl were loaded simultaneously in the thermo-sensitive injectable
      hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug
      loading PECT nanoparticle aqueous dispersions were studied. In vitro release
      profiles of PTX and DOX?HCl and in vivo anti-tumor effect by dual drugs from PECT
      hydrogel were investigated. The results showed that hydrophilic and hydrophobic
      drugs could be successfully entrapped in PECT hydrogel simultaneously without
      affecting its thermo-sensitive behavior. In vitro release profiles demonstrated
      the burst release of DOX?HCl and the sustained release of PTX. Anti-tumor effect
      was improved by a fast and tense attack caused by the burst release of
      hydrophilic DOX?HCl from hydrogel, which was continued by the sequent sustained
      release of PTX-incorporated nanoparticles and remnant DOX?HCl. Unintentionally,
      entrapped in PECT hydrogel, hydrophilic DOX?HCl was observed to have a sustained
      releasing pattern in vitro and in vivo. 

PMID- 24931192
TI  - Constitutive activity in gonadotropin receptors.
AB  - Constitutively active mutants (CAMs) of gonadotropin receptors are, in general,
      rare conditions. Luteinizing hormone-choriogonadotropin receptor (LHCGR) CAMs
      provoke the dramatic phenotype of familial gonadotropin-independent isosexual
      male-limited precocious puberty, whereas in females, there is not yet any
      identified phenotype. Only one isolated follicle-stimulating hormone receptor
      (FSHR) CAM (Asp567Gly) has so far been detected in a single male patient, besides
      other FSHR weak CAMs linked to pregnancy-associated ovarian hyperstimulation
      syndrome or to impaired desensitization and internalization. Several animal
      models have been developed for studying enhanced gonadotropin action; in addition
      to unraveling valuable new information about the possible phenotypes of isolated
      FSHR and LHCGR CAMs in women, the information obtained from these mouse models
      has served multiple translational goals, including the development of new
      diagnostic and therapeutic targets as well as the prediction of phenotypes for
      mutations not yet identified in humans. Mutagenesis and computational studies
      have shed important information on the physiopathogenic mechanisms leading to
      constitutive activity of gonadotropin receptors; a common feature in these
      receptor CAMs is the release of stabilizing interhelical interactions between
      transmembrane domains (TMDs) 3 and 6 leading to an increase, with respect to the
      wild-type receptor, in the solvent accessibility at the cytosolic extension of
      TMDs 3, 5, and 6, which involves the highly conserved Glu/Asp-Arg-Tyr/Trp
      sequence. In this chapter, we summarize the structural features, functional
      consequences, and mechanisms that lead to constitutive activation of gonadotropin
      receptor CAMs and provide information on pharmacological approaches that might
      potentially modulate gonadotropin receptor CAM function.

PMID- 24931193
TI  - Constitutive activities in the thyrotropin receptor: regulation and significance.
AB  - The thyroid-stimulating hormone receptor (TSHR, or thyrotropin receptor) is a
      family A G protein-coupled receptor. It not only binds thyroid-stimulating
      hormone (TSH, or thyrotropin) but also interacts with autoantibodies under
      pathological conditions. The TSHR and TSH are essential for thyroid growth and
      function and thus for all thyroid hormone-associated physiological superordinated
      processes, including metabolism and development of the central nervous system. In
      vitro studies have found that the TSHR permanently stimulates ligand-independent
      (constitutive) activation of Gs, which ultimately leads to intracellular cAMP
      accumulation. Furthermore, a vast variety of constitutively activating mutations
      of TSHR-at more than 50 different amino acid positions-have been reported to
      enhance basal signaling. These lead in vivo to a "gain-of-function" phenotype of
      nonautoimmune hyperthyroidism or toxic adenomas. Moreover, many naturally
      occurring inactivating mutations are known to cause a "loss-of-function"
      phenotype, resulting in resistance to thyroid hormone or hyperthyrotropinemia.
      Several of these mutations are also characterized by impaired basal signaling,
      and these are designated here as "constitutively inactivating mutations" (CIMs).
      More than 30 amino acid positions with CIMs have been identified so far.
      Moreover, the permanent TSHR signaling capacity can also be blocked by inverse
      agonistic antibodies or small drug-like molecules, which both have a potential
      for clinical usage. In this chapter, information on constitutive activity in the
      TSHR is described, including up- and downregulation, linked protein
      conformations, physiological and pathophysiological conditions, and related
      intracellular signaling. 

PMID- 24931194
TI  - Constitutive activity in cannabinoid receptors.
AB  - The cannabinoid receptors are G protein-coupled receptors activated by
      endocannabinoids or exogenous agonist such as tetrahydrocannabinol. Upon agonist
      binding, cannabinoid receptors will activate G proteins of the Gi family, which
      in turn inhibits adenylyl cyclase. Recently, inverse agonists and neutral
      antagonist for cannabinoid receptors have been discovered, demonstrating
      constitutive activity of the cannabinoid receptors. This chapter will discuss the
      current state of the art and provide a framework for evaluating constitutive
      receptor activity and distinguishing constitutive receptor activity from
      constitutive endogenous agonist tone. 

PMID- 24931195
TI  - Constitutive activity in melanocortin-4 receptor: biased signaling of inverse
      agonists.
AB  - The melanocortin-4 receptor (MC4R) is a critical regulator of energy homeostasis,
      including both energy intake and energy expenditure. It mediates the actions of a
      number of hormones on energy balance. The endogenous ligands for MC4R include
      peptide agonists derived from processing of proopiomelanocortin and the
      antagonist Agouti-related peptide (AgRP). Wild-type MC4R has some basal
      (constitutive) activity. Naturally occurring and laboratory-generated mutations
      have been identified, which results in either increased or decreased basal
      activities. Impaired basal signaling has been suggested to be a cause of
      dysregulated energy homeostasis and early-onset obesity, although several
      constitutively active mutations have also been identified from obese patients.
      AgRP and several small-molecule antagonists have been shown to be inverse
      agonists in the Gs-cAMP pathway. However, in the extracellular signal-regulated
      kinase (ERK) 1/2 pathway, we showed that these inverse agonists are potent
      agonists, demonstrating convincingly that they are biased ligands. We also showed
      that some mutations that do not cause constitutive activation in the Gs-cAMP
      pathway cause constitutive activation in the ERK1/2 pathway, suggesting that they
      are biased receptors. The physiological and potential pathophysiological
      relevance of the biased constitutive signaling in MC4R and therapeutic potential
      remain to be investigated. 

PMID- 24931191
TI  - Constitutively active rhodopsin and retinal disease.
AB  - Rhodopsin is the light receptor in rod photoreceptor cells of the retina that
      initiates scotopic vision. In the dark, rhodopsin is bound to the chromophore 11
      cis retinal, which locks the receptor in an inactive state. The maintenance of an
      inactive rhodopsin in the dark is critical for rod photoreceptor cells to remain
      highly sensitive. Perturbations by mutation or the absence of 11-cis retinal can
      cause rhodopsin to become constitutively active, which leads to the
      desensitization of photoreceptor cells and, in some instances, retinal
      degeneration. Constitutive activity can arise in rhodopsin by various mechanisms
      and can cause a variety of inherited retinal diseases including Leber congenital
      amaurosis, congenital night blindness, and retinitis pigmentosa. In this review,
      the molecular and structural properties of different constitutively active forms
      of rhodopsin are overviewed, and the possibility that constitutive activity can
      arise from different active-state conformations is discussed. 

PMID- 24931196
TI  - Constitutive activity in the angiotensin II type 1 receptor: discovery and
      applications.
AB  - The pathophysiological actions of the renin-angiotensin system hormone,
      angiotensin II (AngII), are mainly mediated by the AngII type 1 (AT1) receptor, a
      GPCR. The intrinsic spontaneous activity of the AT1 receptor in native tissues is
      difficult to detect due to its low expression levels. However, factors such as
      the membrane environment, interaction with autoantibodies, and mechanical stretch
      are known to increase G protein signaling in the absence of AngII. Naturally
      occurring and disease-causing activating mutations have not been identified in
      AT1 receptor. Constitutively active mutants (CAMs) of AT1 receptor have been
      engineered using molecular modeling and site-directed mutagenesis approaches
      among which substitution of Asn(111) in the transmembrane helix III with glycine
      or serine results in the highest basal activity of the receptor. Transgenic
      animal models expressing the CAM AT1 receptors that mimic various in vivo disease
      conditions have been useful research tools for discovering the pathophysiological
      role of AT1 receptor and evaluating the therapeutic potential of inverse
      agonists. This chapter summarizes the studies on the constitutive activity of AT1
      receptor in recombinant as well as physiological systems. The impact of the
      availability of CAM AT1 receptors on our understanding of the molecular
      mechanisms underlying receptor activation and inverse agonism is described.

PMID- 24931197
TI  - Constitutive activities and inverse agonism in dopamine receptors.
AB  - The concept of activation in the absence of agonists has been demonstrated for
      many GPCRs and is now solidified as one of the principal aspects of GPCR
      signaling. In this chapter, we review how dopamine receptors demonstrate this
      ability. Although difficult to prove in vivo due to the presence of endogenous
      dopamine and lack of subtype-selective inverse agonists and "pure" antagonists
      (neutral ligands), in vitro assays such as measuring intracellular cAMP,
      [(35)S]GTPgammaS binding, and [(3)H]thymidine incorporation have uncovered the
      constitutive activation of D1- and D2-class receptors. Nevertheless, because of
      limited and inconsistent findings, the existence of constitutive activity for D2
      class receptors is currently not well established. Mutagenesis studies have shown
      that basal signaling, notably by D1-class receptors, is governed by the
      collective contributions of transmembrane domains and extracellular/intracellular
      loops, such as the third extracellular loop, the third intracellular loop, and C
      terminal tail. Furthermore, constitutive activities of D1-class receptors are
      subjected to regulation by kinases. Among the dopamine receptor family, the D5
      receptor subtype exhibits a higher basal signaling and bears resemblance to
      constitutively active mutant forms of GPCRs. The presence of its constitutive
      activity in vivo and its pathophysiological relevance, with a brief mention of
      other subtypes, are also discussed. 

PMID- 24931199
TI  - Constitutively active chemokine CXC receptors.
AB  - Chemokines are low-molecular-weight, secreted proteins that act as leukocyte
      specific chemoattractants. The chemokine family has more than 40 members. Based
      on the position of two conserved cysteines in the N-terminal domain, chemokines
      can be divided into the CXC, C, CC, and CX3C subfamilies. The interaction of
      chemokines with their receptors mediates signaling pathways that play critical
      roles in cell migration, differentiation, and proliferation. The receptors for
      chemokines are G protein-coupled receptors (GPCRs), and thus far, seven CXC
      receptors have been cloned and are designated CXCR1-7. Constitutively active
      GPCRs are present in several human immune-mediated diseases and in tumors, and
      they have provided valuable information in understanding the molecular mechanism
      of GPCR activation. Several constitutively active CXC chemokine receptors include
      the V6.40A and V6.40N mutants of CXCR1; the D3.49V variant of CXCR2; the N3.35A,
      N3.35S, and T2.56P mutants of CXCR3; the N3.35 mutation of CXCR4; and the
      naturally occurring KSHV-GPCR. Here, we review the regulation of CXC chemokine
      receptor signaling, with a particular focus on the constitutive activation of
      these receptors and the implications in physiological conditions and in
      pathogenesis. Understanding the mechanisms behind the constitutive activation of
      CXC chemokine receptors may aid in pharmaceutical design and the screening of
      inverse agonists and allosteric modulators for the treatment of autoimmune
      diseases and cancers.

PMID- 24931198
TI  - Receptor conformation and constitutive activity in CCR5 chemokine receptor
      function and HIV infection.
AB  - The CCR5 chemokine receptor mediates the effects of proinflammatory beta
      chemokines that stimulate chemotaxis, activation, and proliferation of
      macrophages and T cells. CCR5 is also the major coreceptor that mediates HIV
      infection in combination with CD4. Chemokine agonists of CCR5 stimulate the
      activation of cellular calcium and protein kinase signaling pathways that depend
      on the activation of Galphai and probably also Galphaq in some cells. Chemokines
      also stimulate the recruitment of beta-arrestin, which is required for clathrin
      dependent receptor internalization and acts as a scaffold protein for the
      chemotaxis signaling complex that mobilizes the actin cytoskeleton. CCR5 is
      partially constitutively active for the activation of Galphai, but the
      physiological significance has not been studied. HIV binding to CCR5 also
      activates G protein and protein kinase signaling but, in addition, stimulates the
      production of proinflammatory cytokines, including TNF-alpha, and mobilizes the
      actin cytoskeleton to form the fusion pore that allows viral entry and
      subsequently supports viral replication in the cell. The CCR5 conformation that
      mediates the fusion of the viral and cell membranes is unknown, but it is
      probably distinct from the conformation that mediates G protein signaling.
      Nonpeptide CCR5 blockers are allosteric inverse agonists that increase
      dissociation of both chemokines and HIV envelope proteins, but this does not
      correlate with their ability to inhibit HIV infection. Nevertheless, the inverse
      agonist activity may ameliorate the immune activation that exacerbates AIDS
      pathogenesis. Inverse agonists of CCR5 have established efficacy for the
      treatment of AIDS, but may also be useful in preventing HIV infection.

PMID- 24931200
TI  - Constitutive activity of bitter taste receptors (T2Rs).
AB  - G protein-coupled receptors (GPCRs) play a vital role in transmitting an
      extracellular stimuli or signal into an intracellular response in various cells.
      In some scenarios, GPCRs or their mutants can also signal in the absence of an
      agonist or an external stimulus, referred to as basal or constitutive activity,
      and those mutants are termed constitutively active mutants (CAMs). Bitter taste
      is one of the five basic tastes and is mediated by bitter taste receptors (T2Rs),
      which belong to the GPCR superfamily. The 25 T2Rs present in humans do not belong
      to any of the major GPCR classes, and their classification is ambiguous. The
      characterization of T2Rs in many extraoral tissues including the airways and
      upper respiratory tract, where they were shown to cause bronchodilation and
      influence host susceptibility to infection, underscores the therapeutic relevance
      of these receptors. Recent structure-function and pharmacological studies on T2Rs
      led to the identification of CAMs. In this review, we summarize the major
      findings on constitutive activity of T2Rs and their diverse roles. We discuss the
      usefulness of the T2R CAMs in terms of the discovery of bitter taste blockers,
      elucidating the mechanisms of T2R activation and dissecting the physiological
      pathways. 

PMID- 24931202
TI  - Sodium channels, cardiac arrhythmia, and therapeutic strategy.
AB  - Cardiac sodium channels are transmembrane proteins distributed in atrial and
      ventricular myocytes and Purkinje fibers. A large and rapid Na(+) influx through
      these channels initiates action potential and thus excitation-contraction
      coupling of cardiac cells. Cardiac sodium channel is composed of a pore-forming
      alpha-subunit and one or two accessory beta-subunits. The cardiac alpha-subunit
      is encoded by gene SCN5A located on chromosome 3p21. There are four types of beta
      subunits identified so far, and beta1 is the primary beta-subunit in cardiac
      Na(+) channels. The gene responsible for beta1 subunits is SCNB. The expression
      of beta-subunits together with alpha subunits enhances the Na(+) current and
      modifies the channel activities. In addition, interactions of the cardiac Na(+)
      channel with other proteins may facilitate the channel activity and membrane
      expression of the channel. Over the past two decades, molecular genetic studies
      have identified the linkage of gene mutations of the Na(+) channel proteins and
      other regulatory proteins to many inherited arrhythmogenic diseases. The most
      common cardiac arrhythmogenic diseases associated with Na(+) channelopathies are
      long QT syndrome (LQT3) and Brugada syndromes (BrSs). This chapter intends to
      summarize the current understanding of the normal sodium-channel structure and
      function, the gene mutation-associated cardiac arrhythmias, and the current
      diagnosis and management of these diseases.

PMID- 24931204
TI  - Pharmacology and therapeutics of constitutively active receptors. Preface.

PMID- 24931203
TI  - Constitutive activity of the acetylcholine-activated potassium current IK,ACh in
      cardiomyocytes.
AB  - Stimulation of the vagal nerve slows the heart rate and leads to shorter action
      potential duration in the atria. These effects are mainly mediated by binding of
      the vagal neurotransmitter acetylcholine to muscarinic type 2 receptors resulting
      in dissociation of Gi proteins and subsequent activation of IK,ACh-K(+) channels
      due to binding of Gbetagamma-subunits. Even though agonist-independent
      (constitutive) IK,ACh activity is considered negligible in the healthy heart,
      constitutive IK,ACh activity has been shown to contribute to remodeling processes
      associated with cardiac diseases such as atrial fibrillation. In this review, we
      summarize possible mechanisms, which may contribute to the development of
      constitutively active IK,ACh. For example, an increased availability of
      Gbetagamma-subunits within the IK,ACh channel complex could contribute to
      receptor-independent IK,ACh activation. Accordingly, reduced expression of Galpha
      subunits, which act as Gbetagamma-scavengers within the channel complex, and
      increased activity of nucleoside diphosphate kinases, which activate G proteins
      in a receptor-independent manner, are likely contributors to constitutively
      active IK,ACh. In addition, alterations of the IK,ACh channel composition or
      phosphorylation may also be involved in abnormal IK,ACh current activity.
      Finally, we discuss possible therapeutic applications of pharmacological IK,ACh
      modulators, which may represent future drug targets against cardiac diseases such
      as atrial fibrillation. 

PMID- 24931201
TI  - Constitutive activity of the androgen receptor.
AB  - Prostate cancer (PCa) is the most frequently diagnosed cancer in the United
      States. The androgen receptor (AR) signaling axis is central to all stages of PCa
      pathophysiology and serves as the main target for endocrine-based therapy. The
      most advanced stage of the disease, castration-resistant prostate cancer (CRPC),
      is presently incurable and accounts for most PCa mortality. In this chapter, we
      highlight the mechanisms by which the AR signaling axis can bypass endocrine
      targeted therapies and drive progression of CRPC. These mechanisms include
      alterations in growth factor, cytokine, and inflammatory signaling pathways,
      altered expression or activity of transcriptional coregulators, AR point
      mutations, and AR gene amplification leading to AR protein overexpression.
      Additionally, we will discuss the mechanisms underlying the synthesis of
      constitutively active AR splice variants (AR-Vs) lacking the COOH-terminal ligand
      binding domain, as well as the role and regulation of AR-Vs in supporting
      therapeutic resistance in CRPC. Finally, we summarize the ongoing development of
      inhibitors targeting discrete AR functional domains as well as the status of new
      biomarkers for monitoring the AR signaling axis in patients. 

PMID- 24931205
TI  - Sperm involved in recurrent partial hydatidiform moles cannot induce the normal
      pattern of calcium oscillations.
AB  - OBJECTIVE: To assess the Ca2+-releasing ability of sperm involved in partial
      hydatidiform moles. DESIGN: Analysis of the activating and Ca2+-releasing ability
      of human sperm. SETTING: University hospital research laboratory. PATIENT(S):
      Patients undergoing intracytoplasmic sperm injection (ICSI) treatment.
      INTERVENTION(S): Microinjection of mouse and human oocytes with sperm. MAIN
      OUTCOME MEASURE(S): Measurement of the fertilizing and Ca2+-releasing ability of
      human sperm. RESULT(S): The mouse oocyte Ca2+ analysis showed that only 19.0%
      (4/21) of the mouse oocytes injected with sperm involved in molar pregnancies
      exhibited a normal pattern of Ca2+ oscillations versus 63.2% (36/57) of those
      injected with control sperm. Further, 83.3% (15/18) of donated in vitro-matured
      human oocytes injected with deficient sperm did not exhibit any Ca2+ release,
      while 76.9% (10/13) failed to show normal pronuclear development. Yet the sperm
      oocyte activation factor phospholipase C zeta (PLCzeta) was present in the
      majority (96.6%, n=113) of the analyzed sperm at a normal expression level.
      Eventually, fertilization failure was overcome with assisted oocyte activation in
      subsequent therapeutic ICSI cycles, which led to normal deliveries.
      CONCLUSION(S): Sperm that previously provoked recurrent partial hydatidiform mole
      pregnancies due to dispermic fertilization is not able to activate human oocytes
      or trigger the normal pattern of Ca2+ oscillations in mouse and human oocytes in
      vitro.

PMID- 24931207
TI  - Why are we still, 20 years later, depriving human immunodeficiency virus
      serodiscordant couples of equal access to fertility care?

PMID- 24931206
TI  - Temporal and geospatial trends in male factor infertility with assisted
      reproductive technology in the United States from 1999-2010.
AB  - OBJECTIVE: To estimate the prevalence of male factor infertility diagnosis within
      the context of assisted reproductive technology (ART) clinics and its geographic
      and temporal distribution from 1999-2010. DESIGN: Population study based on
      patients presenting for care at ART centers. SETTING: Clinics providing ART
      services. PATIENT(S): All male patients seeking infertility care at ART clinics.
      INTERVENTION(S): Data were obtained from the Centers for Disease Control and
      Prevention, analyzed, geocoded, and mapped. MAIN OUTCOME MEASURE(S): Prevalence
      of male factor infertility diagnosis in a couple seeking infertility care.
      RESULT(S): Between 1999 and 2010, 1,057,402 cycles of ART using nonfrozen,
      nondonor eggs were performed, increasing from 62,809 cycles in 1999 to 99,289
      cycles in 2010. Nationwide in ART clinics, the period prevalence of isolated male
      factor infertility was 17.1% and the prevalence of overall male factor
      infertility diagnoses was 34.6%. The highest prevalence was reported in New
      Mexico (56.4%) and lowest in Mississippi (24.2%). CONCLUSION(S): The prevalence
      of male factor infertility diagnosis varies significantly by time and space
      within the United States, whereas its overall prevalence has remained remarkably
      stable. This study provides the spatial analytic framework for future research to
      explore factors associated with male factor infertility.

PMID- 24931208
TI  - Renal denervation in multiple renal arteries.
AB  - BACKGROUND: In most previous studies investigating efficacy of renal denervation
      (RDN), patients with multiple renal arteries are generally excluded from
      treatment. This study was designed to determine the prevalence of multiple renal
      arteries in patients referred for RDN, to propose a classification for anatomical
      eligibility and to investigate the relation between the presence of multiple
      arteries and blood pressure (BP)-lowering effect. MATERIALS AND METHODS: Patients
      referred for RDN who underwent noninvasive imaging of the renal arteries before
      treatment were included in present analysis. Eligible patients were treated.
      Renal function and BP were evaluated 6 months after treatment. RESULTS: Hundred
      and twenty-six patients referred for RDN were included in present analysis.
      Thirty-four per cent had multiple arteries. Sixty-nine patients underwent RDN.
      Office BP significantly reduced from 195 (+/- 26)/106 (+/- 14) mmHg to 165 (+/-
      24)/95 (+/- 14) mmHg (P < 0.001). BP reduction in patients with multiple arteries
      which were all treated was comparable to patients with solitary arteries.
      However, patients with multiple which were not all treated showed a trend towards
      a less pronounced effect of RDN (beta: 11.6, P = 0.11). The proposed
      classification appeared useful by identifying eligible anatomy. Renal function at
      6 months did not differ from baseline in all subgroups. CONCLUSIONS: Based on our
      results and the high prevalence of multiple arteries, it seems reasonable not to
      exclude patients with multiple renal arteries from RDN. Current analysis suggests
      that BP reduction may be less pronounced in patients with multiple renal arteries
      of whom not all arteries were treated.

PMID- 24931216
TI  - In situ sequencing identifies TMPRSS2-ERG fusion transcripts, somatic point
      mutations and gene expression levels in prostate cancers.
AB  - Translocations contribute to the genesis and progression of epithelial tumours
      and in particular to prostate cancer development. To better understand the
      contribution of fusion transcripts and visualize the clonal composition of
      multifocal tumours, we have developed a technology for multiplex in situ
      detection and identification of expressed fusion transcripts. When compared to
      immunohistochemistry, TMPRSS2-ERG fusion-negative and fusion-positive prostate
      tumours were correctly classified. The most prevalent TMPRSS2-ERG fusion variants
      were visualized, identified, and quantitated in human prostate cancer tissues,
      and the ratio of the variant fusion transcripts could for the first time be
      directly determined by in situ sequencing. Further, we demonstrate concurrent in
      situ detection of gene expression, point mutations, and gene fusions of the
      prostate cancer relevant targets AMACR, AR, TP53, and TMPRSS2-ERG. This unified
      approach to in situ analyses of somatic mutations can empower studies of intra
      tumoural heterogeneity and future tissue-based diagnostics of mutations and
      translocations.

PMID- 24931219
TI  - Animal models of invasive aspergillosis for drug discovery.
AB  - Although Aspergillus infections pose a growing threat to immunocompromised
      individuals, the limited range of existing drugs does not allow efficient
      management of invasive aspergillosis. Moreover, drug resistance is becoming
      increasingly common. Given that drug discovery relies on high-quality animal
      studies, careful design of in vivo models for invasive aspergillosis could
      facilitate the identification of novel antifungals. In this review, we discuss
      key aspects of animal models for invasive aspergillosis, covering laboratory
      animal species, immune modulation, inoculation routes, Aspergillus strains,
      treatment strategies and efficacy assessment, to enable the reader to tailor
      specific protocols for different types of preclinical antifungal evaluation
      study. 

PMID- 24931217
TI  - In vivo enrichment of genetically manipulated platelets corrects the murine
      hemophilic phenotype and induces immune tolerance even using a low multiplicity
      of infection.
AB  - BACKGROUND: Our previous studies have demonstrated that platelet-specific gene
      delivery to hematopoietic stem cells can induce sustained therapeutic levels of
      platelet factor VIII (FVIII) expression in mice with hemophilia A. OBJECTIVE: In
      this study, we aimed to enhance platelet FVIII expression while minimizing
      potential toxicities. METHODS: A novel lentiviral vector (LV), which harbors dual
      genes, the FVIII gene driven by the alphaIIb promoter (2bF8) and a drug
      resistance gene, the MGMT(P140K) cassette, was constructed. Platelet FVIII
      expression in mice with hemophilia A was introduced by transduction of
      hematopoietic stem cells and transplantation. The recipients were treated with
      O(6)-benzylguanine followed by 1,3-bis-2 chloroethyl-1-nitrosourea monthly three
      or four times. Animals were analyzed by using polymerase chain reaction (PCR),
      quantitative PCR, FVIII:C assays, and inhibitor assays. Phenotypic correction was
      assessed by tail clipping tests and rotational thromboelastometry analysis.
      RESULTS: Even using a low multiplicity of infection of 1 and a non-myeloablative
      conditioning regimen, after in vivo selection, the levels of platelet FVIII
      expression in recipients increased to 4.33 +/- 5.48 mU per 10(8) platelets (n =
      16), which were 19.7-fold higher than the levels obtained from the recipients
      before treatment. Quantitative PCR results confirmed that 2bF8/MGMT-LV-transduced
      cells were effectively enriched after drug-selective treatment. Fifteen of 16
      treated animals survived tail clipping. Blood loss and whole blood clotting time
      were normalized in the treated recipients. Notably, no anti-FVIII antibodies were
      detected in the treated animals even after recombinant human B-domain deleted
      FVIII challenge. CONCLUSION: we have established an effective in vivo selective
      system that allows us to enrich 2bF8LV-transduced cells, enhancing platelet FVIII
      expression while reducing the potential toxicities associated with platelet gene
      therapy.

PMID- 24931218
TI  - New advances in treating thrombotic diseases: GPVI as a platelet drug target.
AB  - The recent introduction of highly effective antiplatelet drugs has contributed to
      the significant improvement in the treatment of acute coronary syndromes.
      However, limitations remain. Recurrence of ischaemic vascular events results in
      poor prognosis. Drugs of high antithrombotic efficacy are associated with an
      increased risk of bleeding, which is important in patients at risk of stroke. An
      attractive target for the development of new antithrombotics is platelet
      glycoprotein VI (GPVI) because its blockade seems to combine ideally efficiency
      and safety. In this review, we summarise current knowledge on the physiological
      role of GPVI in haemostasis and thrombosis. We also discuss evidence regarding
      the effectiveness and safety of strategies to inhibit GPVI. 

PMID- 24931220
TI  - Metallothionein, a marker of antiapoptosis, is associated with clinical forms of
      oral lichen planus.
AB  - OBJECTIVES: To investigate the expression of anti- and proapoptosis markers,
      metallothionein (MT), and caspase-2, in the epithelial and inflammatory cells of
      oral lichen planus (OLP) patients, and to investigate the association with
      clinical parameters. MATERIALS AND METHODS: Included were biopsies of 70 OLP
      patients. The clinical data were collected from patients' charts. The expression
      of MT and caspase-2 was immunomorphometrically analyzed in the epithelial and
      inflammatory cells, and the results were correlated with the clinical
      presentation. RESULTS: The epithelial and inflammatory cells expressed MT (10.2
      +/- 5.75 and 0.68 +/- 0.86) and caspase-2 (1.54 +/- 2.6 and 0.98 +/- 1.15) which
      show a trend toward an inverse expression. The expression of MT in the epithelium
      was significantly higher in patients presenting with keratotic lichen planus than
      in patients with the atrophic and erosive forms (P = 0.0008). In the inflammatory
      cells, the expression of MT was inversely correlated with increasing age (R =
      0.34, P = 0.0069). CONCLUSIONS: The pattern of expression of MT and caspase-2 in
      OLP suggests an extensive antiapoptotic response in the keratotic form of the
      disease. Symptomatic patients may benefit from therapy targeted to apoptosis in
      the future.

PMID- 24931222
TI  - Antiferromagnetic Cu-Gd interactions through an oxime bridge.
AB  - The copper complex of a polydentate non-symmetrical Schiff base ligand [LCu]2,
      prepared by template synthesis, has been reacted with the series of lanthanide
      ions. This complex used as a ligand possesses two functions (phenol and oxime)
      able to coordinate the Ln ions and, according to the Ln ion, three types of
      complexes are obtained. From La to Eu, trinuclear [(LCu)2Ln(NO3)3] complexes with
      a double phenoxo-oximato bridge were isolated. From Gd to Ho, the complexes
      [(LCu)2Ln(NO3)3(H2O)] are still trinuclear, with a supplementary water molecule
      linked to the Ln ion but the Cu(II) and Ln(III) ions are only bridged by the
      oximato (N-O) pair, the phenoxo oxygen atom being hydrogen-bridged to the Ln
      coordinated water molecule. Then, with heavier Ln ions, dinuclear
      [(LCu)Ln(NO3)3(H2O)2] complexes are characterized. The magnetic study
      demonstrates that the oximato bridge is responsible for the antiferromagnetic
      character of the Cu-Gd interaction, with JCuGd = -0.63 cm(-1) in
      [(LCu)2Gd(NO3)3(H2O)], in contrast to the ferromagnetic Cu-Gd interaction induced
      by the single oxygen atom phenoxo bridge. 

PMID- 24931221
TI  - Metabolomic profiles delineate the potential role of glycine in gold nanorod
      induced disruption of mitochondria and blood-testis barrier factors in TM-4
      cells.
AB  - Gold nanorods (GNRs) are commonly used nanomaterials with potential harmful
      effects on male reproduction. However, the mechanism by which GNRs affect male
      reproduction remains largely undetermined. In this study, the metabolic changes
      in spermatocyte-derived cells GC-2 and Sertoli cell line TM-4 were analyzed after
      GNR treatment for 24 h. Metabolomic analysis revealed that glycine was highly
      decreased in TM-4 cells after GNR-10 nM treatment while there was no significant
      change in GC-2 cells. RT-PCR showed that the mRNA levels of glycine synthases in
      the mitochondrial pathway decreased after GNR treatment, while there was no
      significant difference in mRNA levels of glycine synthases in the cytoplasmic
      pathway. High content screening (HCS) showed that GNRs decreased membrane
      permeability and mitochondrial membrane potential of TM-4 cells, which was also
      confirmed by JC-1 staining. In addition, RT-PCR and Western blot indicated that
      the mRNA and protein levels of blood-testis barrier (BTB) factors (ZO-1,
      occludin, claudin-5, and connexin-43) in TM-4 cells were also disrupted by GNRs.
      After glycine was added into the medium, the GNR-induced harmful effects on
      mitochondria and BTB factors were recovered in TM-4 cells. Our results showed
      that even low doses of GNRs could induce significant toxic effects on
      mitochondria and BTB factors in TM-4 cells. Furthermore, we revealed that glycine
      was a potentially important metabolic intermediary for the changes of membrane
      permeability, mitochondrial membrane potential and BTB factors after GNR
      treatment in TM-4 cells. 

PMID- 24931223
TI  - Use of biologics in the treatment of hidradenitis suppurativa: a review of the
      Henry Ford Hospital experience.

PMID- 24931224
TI  - Image-guided intraoperative radiation therapy: current developments and future
      perspectives.
AB  - Intraoperative electron beam radiation therapy (IOERT) procedures involve the
      delivery of radiation to a target area during surgery by means of a specific
      applicator. This treatment is currently planned by means of specific systems that
      incorporate tools for both surgical simulation and radiation dose distribution
      estimation. Although the planning step improves treatment quality and facilitates
      follow-up, the actual position of the patient, the applicator and other tools
      during the surgical procedure is unknown. Image-guided navigation technologies
      could be introduced in IOERT treatments, but an innovative solution that
      overcomes the limitations of these systems in complex surgical scenarios is
      needed. A recent publication describes a multi-camera optical tracking system
      integrated in IOERT workflow. This technology has shown appropriate accuracy in
      phantom experiments, and could also be of interest in other surgical
      interventions, where the restrictions solved by this system are also present. 

PMID- 24931225
TI  - Reactive species and oxidative stress in optic nerve vulnerable to secondary
      degeneration.
AB  - Secondary degeneration contributes substantially to structural and functional
      deficits following traumatic injury to the CNS. While it has been proposed that
      oxidative stress is a feature of secondary degeneration, contributing reactive
      species and resultant oxidized products have not been clearly identified in vivo.
      The study is designed to identify contributors to, and consequences of, oxidative
      stress in a white matter tract vulnerable to secondary degeneration. Partial
      dorsal transection of the optic nerve (ON) was used to model secondary
      degeneration in ventral nerve unaffected by the primary injury. Reactive species
      were assessed using fluorescent labelling and liquid chromatography/tandem mass
      spectroscopy (LC/MS/MS). Antioxidant enzymes and oxidized products were semi
      quantified immunohistochemically. Mitophagy was assessed by electron microscopy.
      Fluorescent indicators of reactive oxygen and/or nitrogen species increased at 1,
      3 and 7days after injury, in ventral ON. LC/MS/MS confirmed increases in reactive
      species linked to infiltrating microglia/macrophages in dorsal ON. Similarly,
      immunoreactivity for glutathione peroxidase and haem oxygenase-1 increased in
      ventral ON at 3 and 7days after injury, respectively. Despite increased
      antioxidant immunoreactivity, DNA oxidation was evident from 1day, lipid
      oxidation at 3days, and protein nitration at 7days after injury. Nitrosative and
      oxidative damage was particularly evident in CC1-positive oligodendrocytes, at
      times after injury at which structural abnormalities of the Node of
      Ranvier/paranode complex have been reported. The incidence of mitochondrial
      autophagic profiles was also significantly increased from 3days. Despite modest
      increases in antioxidant enzymes, increased reactive species are accompanied by
      oxidative and nitrosative damage to DNA, lipid and protein, associated with
      increasing abnormal mitochondria, which together may contribute to the deficits
      of secondary degeneration. 

PMID- 24931226
TI  - Commentary on Kamper et. al., juvenile traumatic brain injury evolves into a
      chronic brain disorder: The challenges in longitudinal studies of juvenile
      traumatic brain injury.
AB  - Juvenile traumatic brain injury (TBI) leaves survivors facing a potential
      lifetime of cognitive, somatic and emotional symptoms. A recent study published
      in Experimental Neurology (Kamper et al., 2013) explored the chronic consequences
      of focal brain injury induced in the juvenile animal, extending their previous
      observations out to 6months post-injury. The results demonstrate transient,
      persistent, and late onset behavioral dysfunction, which are associated with
      subtle evidence for enduring histopathology. In line with investigations about
      chronic traumatic encephalopathy from brain injury initiated in the adult,
      juvenile TBI establishes signs of a chronic brain disorder, with unique
      considerations relative to ongoing developmental processes. This commentary
      discusses the challenges in evaluating aging with injury in the juvenile
      population, the current methods of juvenile TBI, and what can be anticipated for
      the future of the field. 

PMID- 24931228
TI  - Aspirin combined with mechanical measures to prevent venous thromboembolism after
      total knee arthroplasty: a randomized controlled trial.
AB  - BACKGROUND: Venous thromboembolism (VTE) is an important complication after major
      orthopedic surgery. Pharmaceutical methods represent the main strategy of VTE
      prevention. The use of aspirin in VTE prevention is still controversial
      worldwide, especially in China. The purpose of this study was to evaluate the
      role of aspirin combined with mechanical measures in the prevention of VTE after
      total knee arthroplasty (TKA). METHODS: Between January 2012 and May 2013 and in
      accordance with the inclusion criteria, 120 patients undergoing TKA were randomly
      allocated to two groups. To prevent VTE, patients in group A received aspirin
      combined with mechanical measures postoperatively, while patients in group B
      received low-molecular-weight heparin (LMWH) sodium and rivaroxaban sequentially
      in combination with mechanical measures postoperatively. All surgeries were
      performed by one surgeon using a posterior-stabilized cemented prosthesis. The
      two groups were followed up and compared for the incidence of deep vein
      thrombosis (DVT) by duplex ultrasound scan and clinical VTE events. The adverse
      events, the blood loss index, and the cost of VTE prevention were also compared.
      RESULTS: DVT was detected in 10 of 60 patients in group A (16.7%, 95% CI: 7.3%
      26.1%) compared with 11 of 60 in group B (18.3%, 95% CI: 8.5%-27.8%) (P = 0.500).
      There is no statistical evidence supporting the inferior effect of aspirin in
      preventing DVT as compared with the other medications. There were no cases of
      symptomatic VTE or death during the follow-up period. Area of ecchymosis was
      lower in group A than in group B, and the differences were statistically
      significant. Patients in group A had the lower blood loss index as compared with
      patients in group B. No transfusion cases were found in both groups. The
      differences were statistically significant. The cost of VTE prevention analysis
      indicated a cost reduction using aspirin in group A compared with using LMWH and
      rivaroxaban in group B. CONCLUSION: Aspirin combined with mechanical measures had
      a good effect on prevention of VTE after TKA and resulted in lower cost, less
      blood loss, and less subcutaneous ecchymosis.

PMID- 24931227
TI  - AutoDock4(Zn): an improved AutoDock force field for small-molecule docking to
      zinc metalloproteins.
AB  - Zinc is present in a wide variety of proteins and is important in the metabolism
      of most organisms. Zinc metalloenzymes are therapeutically relevant targets in
      diseases such as cancer, heart disease, bacterial infection, and Alzheimer's
      disease. In most cases a drug molecule targeting such enzymes establishes an
      interaction that coordinates with the zinc ion. Thus, accurate prediction of the
      interaction of ligands with zinc is an important aspect of computational docking
      and virtual screening against zinc containing proteins. We have extended the
      AutoDock force field to include a specialized potential describing the
      interactions of zinc-coordinating ligands. This potential describes both the
      energetic and geometric components of the interaction. The new force field, named
      AutoDock4Zn, was calibrated on a data set of 292 crystal complexes containing
      zinc. Redocking experiments show that the force field provides significant
      improvement in performance in both free energy of binding estimation as well as
      in root-mean-square deviation from the crystal structure pose. The new force
      field has been implemented in AutoDock without modification to the source code. 

PMID- 24931229
TI  - Human infection with a novel avian-origin influenza A (H7N9) virus: serial chest
      radiographic and CT findings.
AB  - BACKGROUND: Rapidly progressive pneumonia infection with H7N9 virus is a novel
      disease, and limited information is available concerning serial chest
      radiographic and computed tomography (CT) findings. The aim of this study was to
      evaluate the changes in serial radiologic findings in patients with H7N9
      pneumonia. METHODS: The two institutional ethics review boards approved this
      retrospective study. This study included 10 patients with H7N9 pneumonia. All
      patients underwent chest radiologic examinations at different time points. Serial
      radiologic images were systematically analyzed. RESULTS: All patients showed
      abnormal results on initial chest radiography and CT. The initial radiographic
      abnormalities were unilateral (n = 9) and bilateral (n = 1), including ground
      glass opacities (GGOs) (n = 5) and consolidation (n = 5). The initial CT findings
      consisted of unilateral (n = 6) and bilateral (n = 4), including consolidation (n
      = 10), GGOs (n = 10), reticular opacities (n = 2), and pleural effusion (n = 3).
      Follow-up radiologic findings showed rapid development of consolidation or GGOs
      within two weeks after illness onset. Pneumomediastinum with secondary
      subcutaneous emphysema and pneumothorax were noted in two patients. Follow-up
      high resolution computed tomography (HRCT) after two weeks showed slow
      improvement in both size and opacity of the lesions. On HRCT after discharge,
      patients had substantial residual lesions such as irregular linear opacities,
      reticular opacities, parenchymal bands, traction bronchiectasis, and cystic
      lesions. CONCLUSIONS: The most common radiologic findings at presentation are
      multifocal or diffuse areas of consolidation and GGOs in H7N9 pneumonia. HRCT in
      sequence can show more changes in rapid progression of disease and a slow
      decrease of both size and opacity of the lesions plays an important role in the
      evaluation of H7N9 pneumonia.

PMID- 24931230
TI  - Inflammation induced-endothelial cells release angiogenesis associated-microRNAs
      into circulation by microparticles.
AB  - BACKGROUND: Endothelial cells derived microRNAs can be detected in plasma and
      serum and there is evidence that inflammatory disease states may affect the
      levels of circulating microRNAs. However, there is no direct proof that
      inflammation induces endothelial cells to release microRNAs into circulation.
      This study aimed to explore whether inflammation could induce endothelial cells
      to release microRNAs into circulation and to investigate whether these released
      microRNAs derived from endothelial cells were transported in microparticles.
      METHODS: Microparticles were isolated from human atherosclerotic plaques with an
      active inflammatory phenotype and normal vascular tissue. Flow cytometry and real
      time PCR were used to detect the levels of microparticles and microRNAs. Human
      umbilical vein endothelial cells (HUVEC) was treated with tumour necrosis factor
      a (TNF-alpha, 10 ng/ml) for 24 hours, and then HUVEC and the culture medium were
      respectively collected. RESULTS: By comparing microparticles isolated from human
      atherosclerotic plaques with an active inflammatory phenotype (n = 9) and those
      from normal vascular tissues (n = 9), we found levels of annexin V(+)
      microparticles and annexin V(+) CD144(+) microparticles were significantly
      increased in plaques and angiogenesis associated microRNAs (106b, 25, 92a and 21)
      were also significantly increased in microparticles from plaques. After exposure
      to TNF-alpha at a concentration of 10 ng/ml (TNF-alpha group, n = 3) or DMEM
      (control group, n = 3) for 24 hours, counts of microparticles and expressions of
      microRNAs 106b, 25, 92a and 21 in microparticles isolated from medium
      significantly increased. However, there were no differences in the intracellular
      levels of microRNAs 25, 92a or 21 isolated from HUVEC between TNF-alpha group and
      control group, while microRNA 106b decreased in TNF-alpha group. CONCLUSION:
      Inflammation could induce endothelial cells to release angiogenesis associated
      microRNAs into circulation, causing higher levels of circulating endothelial
      cells derived microRNAs in atherosclerosis.

PMID- 24931231
TI  - Soluble CD40 ligand is associated with angiographic severity of coronary artery
      disease in patients with acute coronary syndrome.
AB  - BACKGROUND: Recently, studies have disclosed soluble CD40 ligand (sCD40L) during
      atherosclerosis development and plaque destabilization. The objective of the
      present study was to test the hypothesis that sCD40L levels are higher in acute
      coronary syndrome (ACS) patients with a greater extent of angiographic coronary
      involvement. METHODS: This cross-sectional study examined ACS patients who
      underwent coronary angiography by measuring their sCD40L levels. In order to
      estimate the serum levels of sCD40L, 10 ml of peripheral venous blood was drawn
      within 24 hours of admission. sCD40L levels were measured using an enzyme-linked
      immunosorbent assay (ELISA, RapidBio, West Hills, CA, USA). Demographic data,
      presence of concomitant diseases, ACS characteristics, and angiographic findings
      were evaluated. A review of medical records and patient interviews were conducted
      to assess coronary risk factors. And the severity of coronary artery disease was
      evaluated using the Gensini score index. RESULTS: Two hundred and eighty-nine
      patients were included in the study, of whom 186 were male, with an average age
      of 64.1 +/- 10.0 years. Median sCD40L levels were 1.7 ng/ml (0.3-7.3 ng/ml) and
      Gensini scores were 50 (0-228). After adjusting for demographic variables and
      cardiovascular risk factors, the Gensini score was associated with the natural
      logarithm of the sCD40L level (Coefficient b = 0.002, 95% CI 0.000-0.003, P =
      0.029). CONCLUSION: sCD40L levels were independently associated with angiographic
      severity of coronary artery disease in patients with ACS.

PMID- 24931232
TI  - Exploration of approaches to adjusting brand-name drug prices in Mainland of
      China: based on comparison and analysis of some brand-name drug prices of
      Mainland and Taiwan, China.
AB  - BACKGROUND: Under the circumstance of the New Medical Reform in Mainland of
      China, lowering drug prices has become an approach to relieving increase of
      medical expenses, and lowering brand-name medication price is a key strategy.
      This study, by comparing and analyzing brand-name medication prices between
      Mainland of China and Taiwan, explores how to adjust brand-name medication prices
      in Mainland of China in the consideration of the drug administrative strategies
      in Taiwan. METHODS: By selecting brand-name drug with generic name and dose types
      matched in Mainland and Taiwan, calculate the average unit price and standard
      deviation and test it with the paired t-test. In the mean time, drug
      administrative strategies between Mainland and Taiwan are also compared
      systematically. RESULTS: Among the 70 brand-name medications with generic names
      and matched dose types, 54 are at higher prices in Mainland of China than Taiwan,
      which is statistically significant in t-test. Also, among the 47 medications with
      all of matched generic names, dose types, and manufacturing enterprises, 38 are
      at higher prices in Mainland than Taiwan, and the gap is also statistically
      significant in t-test. In Mainland of China, brand-name medication took cost-plus
      pricing and price-based price adjustment, while in Taiwan, brand-name medication
      took internal and external reference pricing and market-based price adjustment.
      CONCLUSIONS: Brand-name drug prices were higher in Mainland of China than in
      Taiwan. The adjustment strategies of drug prices are scientific in Taiwan and are
      worth reference by Mainland of China.

PMID- 24931233
TI  - Genome-wide association study knowledge-driven pathway analysis of alcohol
      dependence implicates the calcium signaling pathway.
AB  - BACKGROUND: Alcohol dependence (AD) is a serious and common public health
      problem. The identification of genes that contribute to the AD variation will
      improve our understanding of the genetic mechanism underlying this complex
      disease. Previous genome-wide association studies (GWAS) and candidate gene
      genetic association studies identified individual genes as candidates for alcohol
      phenotypes, but efforts to generate an integrated view of accumulative genetic
      variants and pathways under alcohol drinking are lacking. METHODS: We applied
      enrichment gene set analysis to existing genetic association results to identify
      pertinent pathways to AD in this study. A total of 1 438 SNPs (P < 1.0 * 10(-3))
      associated to alcohol drinking related traits have been collected from 31 studies
      (10 candidate gene association studies, 19 GWAS of SNPs, and 2 GWAS of copy
      number variants). RESULTS: Among all of the KEGG pathways, the calcium signaling
      pathway (hsa04020) showed the most significant enrichment of associations (21
      genes) to alcohol consumption phenotypes (P = 5.4 * 10(-5)). Furthermore, the
      calcium signaling pathway is the only pathway that turned out to be significant
      after multiple test adjustments, achieving Bonferroni P value of 0.8 * 10(-3) and
      FDR value of 0.6 * 10(-2), respectively. Interestingly, the calcium signaling
      pathway was previously found to be essential to regulate brain function, and
      genes in this pathway link to a depressive effect of alcohol consumption on the
      body. CONCLUSIONS: Our findings, together with previous biological evidence,
      suggest the importance of gene polymorphisms of calcium signaling pathway to AD
      susceptibility. Still, further investigations are warranted to uncover the role
      of this pathway in AD and related traits.

PMID- 24931234
TI  - Preparation and characterization of paclitaxel-loaded poly lactic acid-co
      glycolic acid coating tracheal stent.
AB  - BACKGROUND: In-stent restenosis caused by airway granulation poses a challenge
      due to the high incidence of recurrence after treatment. Weekly applications of
      anti-proliferative drugs have potential value in delaying the recurrence of
      airway obstruction. However, it is not practical to subject patients to repeated
      bronchoscopy and topical drug applications. We fabricated novel pacilitaxel
      eluting tracheal stents with sustained and slow pacilitaxel release, which could
      inhibit the formation of granulation tissue. And we assessed the quality and drug
      release behaviors of drug-eluting stents (DESs) in vitro. METHODS: Stents were
      dipped vertically into a coating solution prepared by dissolving 0.5 g (2% w/v)
      of poly lactic acid-coglycolic acid (PLGA) and 0.025 g (0.1% w/v) of pacilitaxel
      in 25 ml of dichloromethane. DES morphology was examined by scanning electron
      microscopy (SEM). Pacilitaxel release kinetics from these DESs was investigated
      in vitro by shaking in PBS buffer followed by high performance liquid
      chromatography (HPLC). RESULTS: Using an orthogonal experimental design, we
      fabricated numerous pacilitaxel/PLGA eluting tracheal stents to assess optimum
      coating proportions. The optimum coating proportion was 0.1% (w/v) pacilitaxel
      and 2% (w/v) PLGA, which resulted in total pacilitaxel loading of (16.380 6 +/-
      0.002 1) mg/stent. By SEM the coating was very smooth and uniform. Pacilitaxel
      released from DES was at (0.376 3 +/- 0.003 8) mg/d, which is a therapeutic
      level. There was a prolonged, sustained release of pacilitaxel of >40 days.
      CONCLUSIONS: Paclitaxel-loaded PLGA coating tracheal stents were successfully
      developed and evaluated. Quality assessments demonstrated favorable surface
      morphology as well as sustained and effective drug release behavior, which
      provides an experimental reference for clinical practitioners.

PMID- 24931235
TI  - Effect of maternal age on pregnancy: a retrospective cohort study.
AB  - BACKGROUND: In the last few decades, there has been a delay in first-time
      pregnancies, and the average age of women at the time of delivery has increased
      in many countries. Advanced maternal age is associated with adverse pregnancy
      outcomes. This study aimed to determine the present trends and pregnancy outcomes
      related to maternal age in China. METHODS: Data were collected from 39 hospitals
      in mainland of China. All deliveries were performed after 28 completed weeks of
      gestation and between January 1 and December 31, 2011. In total, 110 450 of 112
      441 cases were included in the study. All enrolled cases were divided into 6 age
      groups with 5-year intervals. The chi(2) test or Fisher's exact test and
      unadjusted binary-Logistic regression were used for statistical analysis.
      RESULTS: The mean age at the time of delivery was 28.18 +/- 4.70 years (range, 14
      52 years). The teenage group (15-19 years) had a higher risk than the 25-29-year
      old group for anemia (odds ratio (OR), 1.4), preeclampsia (OR, 1.6), preterm
      birth (OR, 2.1), low birth weight neonates (OR, 2.3), and perinatal mortality
      (OR, 3.6). The 35-39-year old group and >= 40-year-old group had a higher risk
      than the 25-29-year-old group for leiomyoma (OR, 4.2 vs. 5.8), pregestational
      diabetes (OR, 2.2 vs. 3.8), chronic hypertension (OR, 4.6 vs. 6.5), gestational
      diabetes (OR, 2.6 vs. 3.5), preeclampsia (OR, 2.5 vs. 3.6), premature delivery
      (OR, 1.8 vs. 2.4), postpartum hemorrhage (OR, 1.5 vs. 1.7), placenta previa (OR,
      2.7 vs. 4.0), placental abruption (OR, 1.4 vs. 2.5), cesarean delivery (OR, 2.1
      vs. 2.5), macrosomia (OR, 1.2 vs. 1.2), low birth weight neonates (OR, 1.6 vs.
      2.3), and perinatal mortality (OR, 1.6 vs. 3.7). CONCLUSION: Maternal and
      neonatal risks are higher during the teenage years and at an advanced maternal
      age; 20-30 years of age is the lowest risk period for pregnancy and delivery.

PMID- 24931236
TI  - Detection of abnormalities in dyspneic patients using a new lung imaging
      modality.
AB  - BACKGROUND: Although chest radiography is a useful examination tool, it has
      limitations. Because not all chest conditions can be detected on a radiograph,
      radiography cannot necessarily rule out all irregularities in the chest.
      Therefore, further imaging studies may be required to clarify the results of a
      chest radiograph, or to identify abnormalities that are not readily visible. The
      aim of this study was to compare traditional chest radiography with acoustic
      based imaging (vibration response imaging) for the detection of lung
      abnormalities in patients with acute dyspnea. METHODS: The current investigation
      was a pilot study. Respiratory sounds throughout the respiratory cycle were
      captured using an acoustic-based imaging technique. Consecutive patients who
      presented to the emergency department with acute dyspnea and a normal chest
      radiograph on admission were enrolled and underwent imaging at the time of
      presentation. Dynamic and static images of vibration (breath sounds) and a
      dynamic image score were generated, and assessments were made using an evaluation
      form. RESULTS: In healthy volunteer controls (n = 61), the mean dynamic image
      score was 6.3 +/- 1.9. In dyspneic patients with normal chest radiographs (n =
      51) and abnormal chest radiographs (n = 48), the dynamic image scores were 4.7 +/
      2.7 and 5.1 +/- 2.5, respectively (P < 0.05). The final assessment of the
      vibration images indicated abnormal findings in 15%, 86% and 90% of the
      participants in the above groups, respectively (P < 0.05). CONCLUSIONS: In
      patients with acute dyspnea who present with normal chest radiographs,
      respiratory sound analyses often showed abnormal values. Hence, the ability of
      acoustic-based recordings to offer objective and noninvasive measurements of
      abnormal sound transmission may be useful in the clinical setting for patients
      presenting with acute dyspnea.

PMID- 24931237
TI  - Three transcription factors and the way immune cells affected by different plasma
      change in opposite ways in the development of the syndrome of pre-eclampsia.
AB  - BACKGROUND: How the transcriptional factors regulated the innate and adaptive
      immune system in pregnancy and pre-eclampsia are less understood. Nevertheless,
      what the plasma work in the development of this disease was not sure. The present
      study was design to evaluate what the transcriptional factors change in innate
      and adaptive immune system and what the plasma do in this filed. METHODS:
      Peripheral blood mononuclear cells (PBMC) from non-pregnant women (n = 18), women
      with clinically normal pregnancies (n = 23) and women with pre-eclampsia (n = 20)
      were separated from peripheral blood to isolate monocytes and T cells. The purity
      of monocytes and T cells were analysed by flow cytometry. Monocytes and T cells
      were stimulated in either lipopolysaccharides (LPS) or phorbol-myristate-acetate
      (PMA), respectively. Transcription Factor Arrays were used to screen the
      transcription factors of interest in comparing of different groups. PBMC were
      isolated from another 8 non-pregnant samples were co-incubated with different
      groups of plasma. Polymerase chain reaction (PCR) was performed using whole cell
      extractions of the samples. RESULTS: Nuclear factor of activated T-cells-1 (NFAT
      1), signal transducers and activators of transcription-1 (STAT-1) and activator
      protein-1 (AP-1) are up-regulated in monocytes in pregnancy and more so in pre
      eclampsia. On the the contrary, NFAT-1, STAT-1 and AP-1 are down-regulated in T
      cells in pregnancy and more so in pre-eclampsia. A reduction was observed in
      interferon (IFN)-gamma, interleukin (IL)-12 and IL-4 expression in T cells
      incubated with pre-eclamptic plasma. An elevation was observed in tumor necrosis
      factor (TNF)-alpha, IL-1 and IL-12 expression in monocytes incubated with pre
      eclamptic plasma. CONCLUSIONS: Innate immunity is over activated and adaptive
      immunity is over suppressed in the development of pre-eclampsia. NFAT-1, STAT-1
      and AP-1 might be the central transcription factors in the pathogenesis of pre
      eclampsia. They induced some changes in plasma and "educate" the monocytes and T
      cells for relevant cytokine production. Successful completion of this study will
      enhance our understanding of pre-eclampsia and will discover new knowledge beyond
      pregnancy. The work will inform future therapies for the treatment of a wide
      range of condition such as transplantation immunology and a wide range of immune
      and inflammatory conditions.

PMID- 24931239
TI  - Correlation between the coverage percentage of prosthesis and postoperative
      hidden blood loss in primary total knee arthroplasty.
AB  - BACKGROUND: The aim of this study was to determine the relationship between
      prosthesis coverage and postoperative hidden blood loss (HBL) in primary total
      knee arthroplasty (TKA). METHODS: A total of 120 patients who had undergone
      unilateral TKA from August 2012 to May 2013 were retrospectively studied. The
      Gross formula was used to calculate the amount of HBL. Routine standard
      anteroposterior (AP) and lateral X-ray films of the knee joint were taken
      postoperatively and used to measure the percentages of coronal femoral and of
      coronal and sagittal tibial prosthetic coverage. Then Pearson's correlation
      analysis was performed to assess the correlations between the percentages of
      prosthetic coverage for each AP and lateral position and HBL on the first and
      third postoperative days. RESULTS: The volumes of HBL on the first and third
      postoperative days after TKA were (786.5 +/- 191.6) ml and (1 256.6 +/- 205.1)
      ml, respectively, and lateral X-ray film measurements of percentages of coronal
      femoral, tibial coronal, and sagittal prosthetic coverage were (87.9 +/- 2.5)%,
      (88.5 +/- 2.2)%, and (89.1 +/- 2.3)%, respectively. Pearson's correlation
      analysis showed statistically significant correlations between percentages of
      total knee prosthetic coverage for each AP and lateral position and volumes of
      HBL on the first and third postoperative days (P < 0.05). CONCLUSIONS: HBL after
      TKA correlates with degree of prosthetic coverage. To some extent, the size of
      the surfaces exposed by osteotomy determines the amount of HBL. Choice of the
      appropriate prosthesis can significantly reduce postoperative HBL. Designing
      individualized prostheses would be a worthwhile development in joint replacement
      surgery.

PMID- 24931238
TI  - Feasibility and value of quantitative dynamic contrast enhancement MR imaging in
      the evaluation of sinonasal tumors.
AB  - BACKGROUND: Quantitative dynamic contrast enhancement MR imaging (DCE-MRI), used
      to measure properties of tissue microvasculature and tumor angiogenesis, is a
      promising method for distinguishing benign and malignant tumors and
      characterizing tumor response to antiangiogenic treatment. The aim of this study
      was to assess the feasibility of quantitative parameters derived from clinically
      used DCE-MRI for distinguishing benign from malignant tumors in the sinonasal
      area, which may be potentially useful for prediction and monitoring of treatment
      response to chemoradiotherapy of sinonasal tumors. METHODS: One hundred and forty
      three patients with sinonasal tumors, including 78 malignant tumors and 65 benign
      tumors and tumor-like lesions, underwent clinically used DCE-MRI. Parametric maps
      were obtained for quantitative parameters including K(trans), kep and ve. Two
      radiologists reviewed these maps and measured K(trans), kep and ve in the tumor
      tissue. Data were analyzed using independent T-test or Mann-Whitney U test
      analysis and receiver operating characteristic curves. RESULTS: K(trans), kep and
      ve showed significant differences between benign and malignant tumors in the
      sinonasal area (P = 0.000 1). The accuracy of K(trans), kep and ve in
      differentiation between benign and malignant sinonasal tumors were 72.0%, 76.2%
      and 67.1%, respectively. There were significant differences in kep and ve between
      malignant epithelial sinonasal tumors and lymphomas (P < 0.05). Using a ve value
      of 0.213 as the threshold value differentiated malignant epithelial tumors from
      lymphomas with an accuracy of 78.3%, sensitivity of 88.2%, specificity of 68.0%,
      positive predictive value of 66.7%, and negative predictive value of 90.9%.
      However, no significant difference in K(trans) and kep was found between
      malignant epithelial and non-epithelial tumors in the sinonasal area (P > 0.05).
      CONCLUSIONS: It is feasible that quantitative parameters of tumors can be derived
      from clinically used DCE-MRI in the sinonasal region. Preliminary findings
      suggest an increased value for quantitative DCE-MRI in the evaluation of
      sinonasal tumors in clinical practice.

PMID- 24931240
TI  - Chest radiographic characteristics of community-acquired Legionella pneumonia in
      the elderly.
AB  - BACKGROUND: Legionella is an important community-acquired pneumonia pathogen.
      Although the elderly are especially susceptible to Legionella, few studies have
      looked at comparative radiographic features of Legionella pneumonia in this
      population. The aim of this study was to explore the chest radiographic
      characteristics of community-acquired Legionella pneumonia in the elderly.
      METHODS: Serial chest radiographs obtained in 34 patients hospitalized with
      serologically proven Legionella pneumonia were retrospectively reviewed. Chest X
      ray features of an aged group of >= 65 years were assessed and compared with a
      non-aged group of <65 years old with regard to initial patterns and distributions
      of pulmonary abnormalities, accompanying signs, and progression. RESULTS: The
      most common initial presentation was a patchy alveolar infiltrate involving a
      single lobe, most often the lower lobe. There was no middle or lingular lobe
      involvement in the aged group patients, but bilateral pleural effusion was
      significantly more common in this group. In the aged group patients, radiographic
      progression following adequate therapy, despite a clinical response, was more
      often noted and the radiographs were less likely to have returned to the
      premorbid state at discharge, but the differences were not significant between
      the two groups. CONCLUSION: The discrepancy between imaging findings and clinical
      symptoms seems more prominent in community-acquired Legionella pneumonia in the
      elderly.

PMID- 24931241
TI  - Coronary heart disease: incidence, risk factors and interventions in Jiaozhou of
      Shandong province.
AB  - BACKGROUND: Coronary heart disease (CHD) is the most common type of heart disease
      and cause of heart attacks. This study investigated the epidemiological
      characteristics of CHD and its risk factors in Jiaozhou, Shandong province, to
      ultimately find a way of reducing the prevalence of cardiovascular disease, and
      to provide a theoretical basis for establishing a cardiovascular disease
      management path under the regional medical collaborative mechanism. METHODS: A
      questionnaire survey was performed including 1 952 people aged 35 years or older
      who were questioned by means of stratified, cluster, proportional sampling to
      investigate the prevalence of CHD and its risk factors. The data were inputted
      into SPSS11.0 statistical software for processing and analysis. We advised the
      local medical institutions to establish health files for the residents with CHD
      and risk factors. They were followed up regularly. Their risk factors and life
      style were monitored, and advice was given as to proper medications. Green
      channels were established, and the patients were transmitted in a timely manner
      to superior hospitals for better treatment if the necessary treatments were not
      available in the local hospitals. The control of risk factors was observed after
      the follow-up for half a year. RESULTS: In Jiaozhou, the rates of coronary artery
      disease, hypertension, diabetes, hyperlipidemia and overweight were 8.15%,
      28.54%, 11.43%, 35.46%, and 18.70% respectively. The rates of hypertension,
      diabetes, hyperlipidemia and overweight were higher than the data published in
      "The report of Chinese cardiovascular disease 2012"; which are 24%, 9.7%, 18.6%,
      and 9.7%, respectively. The control of risk factors improved significantly after
      the guidance of the residents lifestyle and medication for six months.
      CONCLUSIONS: The high prevalence of coronary artery disease in Jiaozhou is
      closely related to age, gender, diet structure, family history of cardiovascular
      disease, hypertension, diabetes, hyperlipidemia, overweight, and unhealthy
      lifestyle. Under the regional medical coordination mechanism, the collaborative
      management of cardiovascular disease can provide new management concepts for the
      areas short of medical resources, so as to reduce the prevalence of
      cardiovascular disease.

PMID- 24931242
TI  - Intravitreal ranibizumab therapy versus photodynamic therapy for idiopathic
      choroidal neovascularization: a comparative study on visual acuity, retinal and
      choroidal thickness.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been recommended as a main treatment
      for idiopathic choroidal neovascularization (I-CNV). But the visual results of
      PDT were inconsistent and variable, and PDT may bring severe damage to the
      retinal pigment epithelium and choriocapillaries. In recent years, intravitreal
      ranibizumab therapy, showing favorable visual outcomes, has developed as an
      advanced treatment for choroidal neovascularization (CNV). Although both methods
      have been reported to be effective in treating I-CNV, there is no detailed
      comparative report between the two methods. This study aimed to compare visual
      outcomes, retinal and choroidal thickness between intravitreal ranibizumab
      therapy and PDT in the treatment of I-CNV, and investigate the correlation of
      visual outcomes with retinal and choroidal thickness in each of the two groups.
      METHODS: Thirty-seven eyes of 37 patients with I-CNV were involved in this study;
      19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were
      treated with PDT. The best corrected visual acuity (BCVA) was recorded before and
      at each follow-up visit after treatments (logMAR). Enhanced-depth imaging optical
      coherence tomography (EDI-OCT) was used to evaluate the retinal structural
      changes, and to measure central retinal thickness (CRT) and central choroidal
      thickness (CCT). RESULTS: Mean BCVA was 0.64 +/- 0.27 in PDT group and 0.69 +/-
      0.22 in ranibizumab group at baseline (P = 0.55). When compared with the
      baseline, mean BCVA in PDT group was improved significantly at 3-month after PDT
      (0.41 +/- 0.16, P = 0.002), then changed little (0.42+/-0.25 at 12-month, P =
      0.88). Whereas mean BCVA in Ranibizumab group was improved significantly at each
      follow-up visit. It improved much more obviously in the first month and then
      remained stable. The mean BCVA in the ranibizumab group was significantly better
      at each follow-up visit than that in PDT (P < 0.05). When compared with the
      baseline, mean CRT in PDT group decreased significantly since 3-month visit,
      whereas mean CRT in ranibizumab group decreased significantly from 1-month visit.
      Mean CRT at 1-month and 3-month decreased much more in ranibizumab group than
      that in PDT group, almost in the same period as BCVA improving. When compared
      with the baseline, mean CCT did not change significantly at each follow-up visit
      in each group (P > 0.05). The CCT difference was not statistically significant
      between the two groups at each same time visit (P > 0.05). Mean BCVA was
      correlated with CRT, but was not correlated with CCT. CONCLUSIONS: Both
      intravitreal ranibizumab therapy and PDT are effective for the treatment of I
      CNV. It is obvious that ranibizumab therapy is significantly superior to PDT in
      improving BCVA and decreasing CRT. CRT decreases much more rapidly in ranibizumab
      group than in PDT group, simultaneously with visual improvement. CRT reduction
      has significant correlation with the visual outcomes in the recovery of I-CNV,
      whereas BCVA prognosis may have no correlation with CCT. CCT is not changed
      significantly after each of the treatments. Both PDT and ranibizumab therapy may
      have no significant effect on choroid.

PMID- 24931243
TI  - Epidemiological characteristics of thyroid nodules and risk factors for malignant
      nodules: a retrospective study from 6,304 surgical cases.
AB  - BACKGROUND: The prevalence of thyroid nodules (TN) is increasing rapidly. This
      study analyzed the epidemiological and clinical characteristics of TN in
      surgically treated patients and identified the risk factors for malignant nodules
      (MN) to provide more understanding of the differential diagnosis of TN. METHODS:
      A total of 6 304 TN cases who underwent thyroid surgery were included in this
      retrospective study. The clinical data were collected to evaluate the clinical
      and epidemiological characteristics and related risk factors for MN. The nature
      of TN (benign nodules (BN) or MN), medical records, laboratory data, and imaging
      data were analyzed. The risk factors for MN were screened using Spearman's rank
      correlation analysis and nonconditional binary Logistic regression analysis.
      RESULTS: The number of surgically treated TN cases increased yearly. A total of
      34.33% of cases were MN and 65.67% were BN. Up to 56.74% of these cases underwent
      unnecessary surgery. Among the MN cases, papillary thyroid carcinoma accounted
      for 94%, in which 46.71% coexisted with benign thyroid disease and 32.28% with
      multiple foci. Single-related factor analysis showed that age, employment,
      disease duration, history of breast nodules and/or hypertension, the levels of
      serum thyroid-stimulating hormone (TSH), thyroglobulin antibody (TgAb), and
      thyroid peroxidase antibody (TPoAb), and ultrasound features of TN were related
      to MN. Stepwise nonconditional binary Logistic regression analysis showed that 13
      factors may be the independent risk factors for MN, including <40 years old,
      previous history of breast nodules and/or hypertension, disease duration <1
      month, employment, hypoechoic nodule, irregular nodules, nodule calcification,
      solid echo nodule, fuzzy boundary, rich blood flow within nodules, abnormal lymph
      nodes around the neck, nodule diameter <1 cm, and abnormally high TgAb.
      CONCLUSIONS: Our results demonstrate a rapid increase in surgically treated TN
      cases and ratio of MN and indicate unnecessary surgeries in some cases. This
      study also suggest that age, duration of thyroid disease, history of breast
      disease and/or hypertension, the levels of serum TSH, TgAb, and TPoAb, and
      ultrasound features of TN are related to MN, and some of these factors may be the
      risk factors for MN.

PMID- 24931244
TI  - Aortic rupture during radiofrequency catheter ablation of left ventricular
      tachycardia.

PMID- 24931245
TI  - Urinary albumin excretion rate: a risk factor for retinal hard exudates in
      macular region in type 2 diabetic patients.
AB  - BACKGROUND: The various risk factors for retinal hard exudates are still poorly
      understood in type 2 diabetic patients. The aim of this study was to determine
      the association between urinary albumin excretion rate (UAER) and hard exudates
      in macular region in north Chinese patients. METHODS: A total of 272 patients
      (272 eyes) were enrolled for this study, including 154 subjects from group 1
      (mild hard exudates), 91 subjects from group 2 (moderate hard exudates) and 27
      subjects from group 3 (severe hard exudates) confirmed using colour fundus
      photography, optical coherence tomography (OCT) as well as slit-lamp
      biomicroscopy with 78 diopter (D) lens. Each participant underwent a
      comprehensive assessment that included biochemical, clinical characteristics test
      and detailed ophthalmic evaluation. One-way analysis of variance (ANOVA) test and
      chi-square test were performed to analyze the fasting blood glucose (FBG),
      glycated hemoglobin (HbA1c), total cholesterol (TC), low density lipoprotein
      (LDL), high density lipoprotein (HDL), triglycerides (TG), full blood counts,
      urinary albumin excretion rate (UAER), blood creatinine (CREA), duration of
      diabetes, body mass index (BMI), systolic blood pressures (SBP) and diastolic
      blood pressures (DBP) between groups. Ordinal logistic regression analysis was
      further performed in order to eliminating the possible confounding factors.
      RESULTS: Three groups were matched in terms of age and gender. Risk factors which
      showed significant difference between groups include FBG (P < 0.001), HbA1c (P <
      0.001), LDL (P < 0.001), UAER (P < 0.001), duration of diabetes (P = 0.001), TC
      (P = 0.005), SBP (P = 0.026), CREA (P = 0.004) and haemoglobin (Hb) (P = 0.012).
      There was no significant difference between groups for the TG, HDL, DBP,
      platelet, total white blood cells and BMI. Using ordinal Logistic regression
      analyses, of all the variables, HbA1c, LDL and UAER which were independent risk
      factor for hard exudates showed a significantly odds ratio of 1.25, 3.07, and
      1.39, respectively. There were also significant differences in UAER level between
      patients with mild, moderate, severe hard exudates groups (P < 0.001).
      CONCLUSIONS: UAER was an independent risk factor associated with retinal hard
      exudates in macular region in type 2 diabetic patients. This study highlights the
      need for close monitoring and fundus examination for hard exudates in patients
      with elevated UAER to prevent irreversible visual loss.

PMID- 24931246
TI  - Preoperative prediction of survival in resectable gallbladder cancer by a
      combined utilization of CA 19-9 and carcinoembryonic antigen.
AB  - BACKGROUND: Currently, all frequently used staging systems in gallbladder cancer
      (GBC) are based on postoperative pathological examinations. In patients
      undergoing curative operation, there is no effective method to predict survival
      preoperatively. In this study, we explored whether a combined utilization of two
      tumor biomarkers, namely carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic
      antigen (CEA), could give a preoperative prediction of survival in resectable
      GBC. METHODS: Seventy-three patients who underwent radical resection for GBC were
      included in this study. A retrospective analysis of clinical-pathological data
      was conducted. RESULTS: By multivariate analysis, CA 19-9 elevation (P < 0.05)
      and CEA elevation (P < 0.001) were discovered as two individual factors for
      postoperative survival. By a combined utilization, patients were divided into
      three groups: patients with elevation of CEA (group I), patients with elevation
      of CA 19-9 but without CEA (group II), and patients with nonelevations of either
      CA 19-9 or CEA (group III). The cumulative 5-year survival rates in groups I, II,
      and III were 0, 14.0%, and 42.8%, respectively (P < 0.05). CONCLUSIONS: By a
      combined utilization of CA 19-9 and CEA, individualized prediction of survival is
      available in resectable GBC before operation. Extended radical operation brings
      the most prognostic benefits in patients with nonelevations of either CA 19-9 or
      CEA. However, if operation would be in a larger-scale destructive manner, careful
      consideration of surgical decisions should be made in patients with elevation of
      tumor biomarkers, especially CEA.

PMID- 24931247
TI  - Audiological evaluation in Chinese patients with mitochondrial
      encephalomyopathies.
AB  - BACKGROUND: Hearing impairment has been reported to be common in patients with
      mitochondrial disorders, a group of diseases characterized by pleiomorphic
      clinical manifestations due to defects in oxidative phosphorylation of
      mitochondria. This study aimed to investigate the audiological characteristics in
      a large cohort of patients with mitochondrial disease. METHODS: Comprehensive
      audiological evaluations, including pure tone audiometry, tympanometry, speech
      audiometry, otoacoustic emissions, electrocochleography and auditory brainstem
      evoked potentials, were performed in 73 Chinese patients with mitochondrial
      encephalomyopathy and with confirmed mitochondrial DNA (mtDNA) defects. RESULTS:
      Among the patients, 71% had hearing impairment. However, the incidence rate and
      severity of hearing impairment were much less in the chronic progressive external
      ophthalmoplegia (CPEO) subtype than in the mitochondrial encephalomyopathy,
      lactic acidosis, and stroke-like episodes (MELAS), myoclonic epilepsy with ragged
      red fibers (MERRF) and Kearns-Sayre syndrome (KSS) subtypes. While most of our
      patients had a predominantly cochlea origin for the hearing deficit, five
      patients had an auditory neuropathy spectrum disorder and three patients had
      impairment of both cochlea and auditory cortex. CONCLUSIONS: Various portions of
      the auditory system could be involved in patients with mitochondrial diseases,
      including cochlea, auditory nerve, auditory pathway and cortex. Hearing loss was
      more associated with multisystem involvement. Genotype, mutant load of mtDNA and
      other unknown factors could contribute to heterogeneity of hearing impairment in
      mitochondrial disease.

PMID- 24931248
TI  - Fourth-generation ceramic-on-ceramic total hip arthroplasty in patients of 55
      years or younger: short-term results and complications analysis.
AB  - BACKGROUND: The incidence of total hip replacement in the younger and more active
      patients is ever increasing. The ceramic-on-ceramic (COC) bearing was developed
      to reduce wear debris-induced osteolysis and loosening and to improve the
      longevity of hip arthroplasties. Few studies have reported the clinical results
      and complications of the new zirconia-toughened ceramic total hip arthroplasty
      (THA). METHODS: A consecutive series of 132 young patients (177 hips) that
      underwent primary cementless THAs between January 2010 and December 2012 were
      included in this study. These arthroplasties all had fourth-generation COC
      bearings performed through a posterolateral approach. The average age was (41.8
      +/- 8.3) years (ranging from 22 to 55 years), and the mean follow-up period was
      (24.5 +/- 9.4) months (ranging from 12 to 47 months). The results were evaluated
      both clinically and radiographically. Harris hip score (HHS) was determined
      before surgery and at the time of each follow-up. Presence of postoperative groin
      or thigh pain and squeaking were recorded. Other complications such as
      dislocations, periprosthetic fractures, and ceramic components fractures were
      diagnosed and treated in emergency. RESULTS: The average HHSs improved from
      preoperative 60.3 +/- 10.7 (ranging from 29 to 76) to 91.0 +/- 5.1 (ranging from
      74 to 100) at the final follow-up (t = 45.064, P < 0.05), and 97.7% of cases were
      scored as excellent and good results. At the last follow-up, incidental inguinal
      pain was found in three hips (1.7%) and thigh pain in 11 hips (6.2%). Radiographs
      showed a high rate of new bone formation around the acetabular and stem
      components. No obvious osteolysis or prosthesis loosening was detected.
      Complications occurred in six hips (3.4%): posterior dislocation in two hips
      (1.1%), periprosthetic femoral fracture in one hip (0.6%), asymptomatic squeaking
      in two hips (1.1%), and ceramic liner fracture in one hip (0.6%). CONCLUSIONS:
      The fourth-generation COC THA showed excellent clinical results in younger active
      patients with no osteolysis-related prosthesis failure at a short-term follow-up
      study. Surgeons should still be aware of the potential risks of complications
      such as dislocation, periprosthetic fracture, squeaking, and ceramic components
      fracture.

PMID- 24931249
TI  - Effects of exercises on knee cartilage volume in young healthy adults: a
      randomized controlled trial.
AB  - BACKGROUND: Acute effects of physical exercise on the deformational behavior of
      knee articular cartilage and changes in cartilage volume are definite. However,
      conclusive effects of different exercises on the loss of articular cartilage
      volume have not been proved. In this parallel-group randomized controlled trial,
      we tested whether 12 weeks of swimming, powerstriding, cycling, and running
      exercises would decrease the cartilage volume significantly and whether there
      would be a difference in the loss of cartilage volume after different types of
      exercises. METHODS: From October 2012 to January 2013 we evaluated 120 healthy
      volunteer students in Biomechanics Laboratory of Tongji University. Body mass
      index (BMI), right lower limb strength, and right knee cartilage magnetic
      resonance imaging (MRI) were obtained before exercise. MRI were conducted in East
      Hospital. The study was approved by Tongji University Ethical Committee, all
      subjects were randomly assigned to the running, powerstriding, cycling, swimming,
      and control groups by a drawing of lots. Each group contained 24 samples. At the
      end of 12 weeks of regular exercises, the same measurement procedures were
      applied. Cartilage volume was calculated with OSIRIS software based on the
      quantitative-MRI. Pre- and post-exercise comparisons were carried out using
      paired t-tests and one-way analysis of variance (ANOVA) was used to compare
      differences of cartilage volume loss between groups with Student-Newman-Keuls
      procedure for multiple comparisons. RESULTS: Running, cycling, and swimming
      groups resulted in a significant decrease in BMI. The quadriceps peak torque
      increased significantly in the swimming and cycling groups. Total cartilage
      volume significantly decreased in the running and cycling groups after 12 weeks
      of training, without any significant change in the nonimpact swimming, low-impact
      powerstriding, and control groups. Loss of total cartilage volume in the running
      and cycling groups were 2.21% (3.03) and 1.50% (0.42). CONCLUSIONS: Twelve weeks
      of regular physical exercises (i.e., running and cycling) decrease the total knee
      cartilage volume. Swimming and powerstriding are recommended for the healthy
      youth. This finding suggests that articular cartilage has the functional
      adaptation for exercises, and some sports could be the risk factors for the
      initiation of osteoarthritis (OA) in young healthy adults.

PMID- 24931250
TI  - Uterine artery embolization in cesarean scar pregnancy: safe and effective
      intervention.
AB  - BACKGROUND: Cesarean scar pregnancy (CSP) is a very rare but life-threatening
      entity and there is no optimal management strategy. Here we report a successfully
      conservative treatment of CSP. METHODS: We retrospectively analyzed the clinical
      data of 54 women with CSP, who underwent uterine artery embolization between
      January 2007 and September 2012 at the Peking University People's Hospital. We
      evaluated the clinical outcomes, the technique and the complications of uterine
      artery embolization. RESULTS: Of the 54 patients, 2 patients with hemorrhage
      after induced abortion received bilateral uterine artery embolization treatment
      alone, and 52 patients underwent suction curettage after bilateral uterine artery
      embolization. All 54 women were successfully cured, without any severe
      complications, and uterine function was restored. During the follow-up, one
      patient had accidental normal interuterine pregnancy and received induced
      abortion during the first trimester. CONCLUSION: [corrected] Uterine artery
      embolization combined with suction curettage is an effective and safe
      conservative treatment for cesarean scar pregnancy.

PMID- 24931251
TI  - Distinct characteristics and new prognostic scoring system for Chinese patients
      with Waldenstrom macroglobulinemia.
AB  - BACKGROUND: Waldenstrom macroglobulinemia (WM) is an uncommon lymphoid
      malignancy. The characteristics and prognosis of WM have never been
      systematically studied in the East. METHODS: We analyzed the clinical
      characteristics and the prognostic factors of 90 Chinese WM patients, and
      compared them with the Western reports. RESULTS: The median age was 62 years old
      with a male-to-female ratio of 3.74. The most common symptoms at diagnosis were
      fatigue (77.8%) and bleeding (20%), while only 6 patients (6.7%) were
      asymptomatic. In the univariate analysis, age >62 years, thrombocytopenia,
      leucopenia, cytopenias >= 2, and high risk on the international prognostic
      scoring system for WM were the adverse risk factors, but only age >62 years and
      >= 2 cytopenias were the independent prognostic factors in the multivariate
      analysis. Using age <62 years and >= 2 cytopenias, three significantly different
      prognostic groups could been distinguished, with 5-year overall survival of
      71.6%, 48.6%, and 17.0% (P < 0.001). CONCLUSION: Distinct characteristics exist
      in WM in China compared to the West and we describe a new simple prognostic model
      for newly diagnosed WM patients.

PMID- 24931252
TI  - Age, estimated glomerular filtration rate and ejection fraction score predicts
      contrast-induced acute kidney injury in patients with diabetes and chronic kidney
      disease: insight from the TRACK-D study.
AB  - BACKGROUND: The occurrence of contrast induced acute kidney injury (CIAKI) has a
      pronounced impact on morbidity and mortality. The aim of the present study was to
      appraise the diagnostic efficacy of age, estimated glomerular filtration rate
      (eGFR) and ejection fraction (AGEF) score (age/EF(%)+1 (if eGFR was <60 ml * min(
      1)* 1.73 m(-2))) as an predictor of CIAKI in patients with diabetes mellitus (DM)
      and concomitant chronic kidney disease (CKD). METHODS: The AGEF score was
      calculated for 2 998 patients with type 2 DM and concomitant CKD who had
      undergone coronary/peripheral arterial angiography. CIAKI was defined as an
      increase in sCr concentration of 0.5 mg/dl (44.2 mmol/L) or 25% above baseline at
      72 hours after exposure to the contrast medium. Post hoc analysis was performed
      by stratifying the rate of CIAKI according to AGEF score tertiles. The diagnostic
      efficacy of the AGEF score for predicting CIAKI was evaluated with receiver
      operating characteristic (ROC) analysis. RESULTS: The AGEF score ranged from 0.49
      to 3.09. The AGEF score tertiles were defined as follows: AGEFlow <= 0.92 (n = 1
      006); 0.92 <AGEFmid <= 1.16 (n = 1 000), and ACEFhigh >1.16 (n = 992). The
      incidence of CIAKI was significantly different in patients with low, middle and
      high AGEF scores (AGEFlow = 1.1%, AGEFmid = 2.3% and AGEFhigh = 5.8%, P < 0.001).
      By multivariate analysis, AGEF score was an independent predictor of CIAKI (odds
      ratio = 4.96, 95% CI: 2.32-10.58, P < 0.01). ROC analysis showed that the area
      under the curve was 0.70 (95% CI: 0.648-0.753, P < 0.001). CONCLUSION: The AGEF
      score is effective for stratifying risk of CIAKI in patients with DM and CKD
      undergoing coronary/peripheral arterial angiography. (Clinical Trial identifier:
      NCT00786136).

PMID- 24931253
TI  - Construction of plasmid vector pAFP-HSVtk-IRES2-EGFP and its effect on the
      cytotoxicity of ganciclovir to hepatocellular carcinoma.
AB  - BACKGROUND: Herpes simplex virus thymidine kinase phosphorylates ganciclovir to
      ganciclovir monophosphate, which is then converted to ganciclovir triphosphate by
      endogenous cellular nucleoside kinases. The ganciclovir triphosphate acts as a
      DNA chain terminator due to the lack of a functional 3'-OH group and terminates
      the process of DNA replication, hence leading to cell apoptosis. At present,
      HSVtk gene usually acts as suicide gene to kill tumor cells. The aim of this
      study was to investigate the selective cytotoxicity of the herpes simplex virus
      thymidine kinase/ganciclovir (HSVtK/GCV) suicide gene system controlled by the a
      fetoprotein (AFP) promoter on hepatocellular carcinoma (HCC) cells in vitro.
      METHODS: pAFP-HSVtk-IRES2-EGFP recombinant plasmid vectors driven by the AFP
      promoter were constructed. HL-7702 liver cells, HUH-7 HCC, and HepG2 HCC were
      transfected with the recombinant plasmids. HSVtK gene expression was detected
      using Western blotting analysis. HepG2 cells line stably expressing HSVtk gene
      was selected by G418 reagent. The cytotoxicity of HSVtK/GCV suicide gene system
      on hepatoma cells was measured by CCK-8 reagents when different doses of
      ganciclovir were added. RESULTS: Plasmid pAFP-TK-IRES2-EGFP-expressed HSVtk gene
      was constructed successfully. HSVtk gene expression level was significantly
      higher in AFP-positive hepatoma cells than in AFP-negative liver cells. After
      G418 selection, a HepG2 cells line stably expressing HSVtk gene was acquired.
      With the increase of the dose of ganciclovir the optical density at 450 nm of
      HepG2 cells stably expressing HSVtk gene gradually decreased (P < 0.05).
      CONCLUSION: The HSVtK gene-specific expression in hepatoma cells as well as the
      cytotoxicity of the suicide gene system in HepG2 cells provided the basis for the
      targeted gene therapy of HCC.

PMID- 24931254
TI  - Decrease in myostatin by ladder-climbing training is associated with insulin
      resistance in diet-induced obese rats.
AB  - BACKGROUND: Suppression of myostatin (MSTN) has been associated with skeletal
      muscle atrophy and insulin resistance (IR). However, few studies link MSTN
      suppression by ladder-climbing training (LCT) and IR. Therefore, we intended to
      identify the correlation with IR between LCT and to analyze the signaling
      pathways through which MSTN suppression by LCT regulates IR. METHODS: The rats
      were randomly assigned to two types of diet: normal pellet diet (NPD, n = 8) and
      high-fat diet (HFD, n = 16). After 8 weeks, the HFD rats were randomly re
      assigned to two groups (n = 8 for each group): HFD sedentary (HFD-S) and high-fat
      diet ladder-climbing training (HFD-LCT). HFD-LCT rats were assigned to LCT for 8
      weeks. Western blotting, immunohistochemistry and enzyme assays were used to
      measure expression levels and activities of MSTN, GLUT4, PI3K, Akt and Akt
      activated targets (mTOR, FoxO1 and GSK-3beta). RESULTS: The LCT significantly
      improved IR and whole-body insulin sensitivity in HDF-fed rats. MSTN protein
      levels decreased in matching serum (42%, P = 0.007) and muscle samples (25%, P =
      0.035) and its receptor mRNA expression also decreased (16%, P = 0.041) from
      obese rats after LCT. But the mRNA expression of insulin receptor had no obvious
      changes in LCT group compared with NPD and HFD-S groups (P = 0.074). The ladder
      climbing training significantly enhanced PI3K activity (1.7-fold, P = 0.024) and
      Akt phosphorylation (83.3%, P = 0.022) in HFD-fed rats, significantly increased
      GLUT4 protein expression (84.5%, P = 0.036), enhanced phosphorylation of mTOR
      (4.8-fold, P < 0.001) and inhibited phosphorylation of FoxO1 (57.7%, P = 0.020),
      but did not affect the phosphorylation of GSK-3beta. CONCLUSIONS: The LCT
      significantly reduced IR in diet-induced obese rats. MSTN may play an important
      role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and
      PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.

PMID- 24931255
TI  - Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic
      delivery vehicles of myxoma virus.
AB  - BACKGROUND: Gallbladder carcinoma (GBC) has a high mortality rate, requiring
      synergistic anti-tumor management for effective treatment. The myxoma virus
      (MYXV) exhibits a modest clinical value through its oncolytic potential and
      narrow host tropism. METHODS: We performed viral replication assays, cell
      viability assays, migration assays, and xenograft tumor models to demonstrate
      that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous
      MYXV delivery. RESULTS: We examined the permissiveness of various GBC cell lines
      towards MYXV infection and found two supported single and multiple rounds of MYXV
      replication, leading to an oncolytic effect. Furthermore, we found that BMSCs
      exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed
      to affect the growth of GBC cells, in terms of tumor volume and survival time.
      Finally, we demonstrated in vivo that intravenous injection of MYXV-infected
      BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the
      same extent as intratumoral injection of MYXV. CONCLUSION: This study indicates
      that BMSCs are a promising novel vehicle for MYXV to clinically address
      gallbladder tumors.

PMID- 24931256
TI  - MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by
      targeting IGF1R and BCL2.
AB  - BACKGROUND: Studies have shown that the drug resistance of gastric cancer cells
      can be modulated by abnormal expression of microRNAs (miRNAs). We investigated
      the role of miR-503 in the development of cisplatin resistance in human gastric
      cancer cell lines. METHODS: MiR-503 expression was measured by quantitative real
      time PCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and
      clonogenic assays were used to examine changes in cell viability and the drug
      resistance phenotype of cancer cells associated with upregulation or
      downregulation of the miRNA. A dual-luciferase activity assay was used to verify
      target genes of miR-503. Immunohistochemistry, Western blotting analysis, and a
      flow cytometric apoptosis assay were used to elucidate the mechanism by which miR
      503 modulates drug resistance in cancer cells. RESULTS: MiR-503 was significantly
      downregulated in gastric cancer tissues and several gastric cancer cell lines.
      Additionally, downregulation of miR-503 in the cisplatin (DDP)-resistant gastric
      cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like
      growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared
      with the parental SGC7901 cell line. An in vitro drug sensitivity assay showed
      that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin. The
      luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions
      in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes
      of miR-503. Enforced miR-503 expression in SGC7901/DDP cells reduced expression
      of the target proteins, inhibited proliferation, and sensitized the cells to DDP
      induced apoptosis. CONCLUSION: Our findings suggest that hsa-miR-503 modulates
      cisplatin resistance of human gastric cancer cells at least in part by targeting
      IGF1R and BCL2.

PMID- 24931257
TI  - Effect of cigarette smoke extraction on the expression of found in inflammatory
      zone 1 in rat lung epithelial L2 cells.
AB  - BACKGROUND: Found in inflammatory zone 1 (FIZZ1) protein increased in pulmonary
      epithelial cells and in limited amounts of other lung cells. FIZZ1 increased in
      murine model of smoke induced chronic obstructive pulmonary disease. However, the
      direct role of FIZZ1 produced by pulmonary epithelium stimulated with cigarette
      smoke extraction has not been determined. We examined the expression and function
      of FIZZ1 in rat lung epithelial L2 cells. METHODS: The rat lung epithelial L2
      cells (CCL 149) were exposed to cigarette smoke extraction, expression of FIZZ1
      mRNA was investigated by RT-PCR. Levels of FIZZ1 protein were detected by Western
      blotting and laser confocal microscope. CCL 149 cells were treated with different
      concentrations and for different time of recombinant protein FIZZ1. After
      treatment, the expression levels of interleukin 8 (IL-8) were detected by enzyme
      linked immunosorbent assay (ELISA). RESULTS: When CCL 149 cells were exposed to
      cigarette smoke extraction, FIZZ1 mRNA and protein levels expressed significantly
      higher than control group. Recombinant protein FIZZ1 promoted the expression of
      IL-8 in a dose and time dependent manner in a certain range. CONCLUSIONS:
      Cigarette smoke extraction activates FIZZ1 at mRNA and protein levels in CCL 149
      cells. Recombinant protein FIZZ1 induces the expression of IL-8 and may thus
      participate in the process of chronic obstructive pulmonary disease airway
      inflammation and airflow obstruction. Generally, immune cells such as
      macrophages, neutrophils and lymphocytes are unavoidably involved in airway
      inflammatory and immune responses to cigarette smoke, but it is still unclear
      whether their involvement in the pathogenesis of chronic obstructive pulmonary
      disease is based on the specific expression in lung epithelial cells of FIZZ1.

PMID- 24931258
TI  - Efficacy of thalidomide on trinitrobenzene sulfonate-induced colitis in young
      rats and its mechanism.
AB  - BACKGROUND: Thalidomide could relieve clinical symptoms and intestinal mucosal
      lesions effectively in children with refractory inflammatory bowel disease (IBD)
      from the pre-clinical study. This study aimed to observe the therapeutic effect
      of thalidomide by the established animal model of IBD model of 2,4,6
      trinitrobenzene sulfonic acid (TNBS)-induced colitis in Sprague-Dawley (SD) rats
      and to investigate the possible mechanism of action. METHODS: A total of 82 SD
      rats of about 4-5 weeks were randomly divided into three groups: the control
      group (25 rats), TNBS-treated group (29 rats), and thalidomide treatment group
      (28 rats). Daily activities were recorded. At least eight rats from each group
      were killed on the 4th, 7th, and 14th days. Morphological and histological
      changes in the colon were individually assessed. Serum was collected and the
      levels of TNF-alpha and interleukins (IL-1beta and IL-10) were assayed by ELISA
      method. The expression of colonic mucosal nuclear factor (NF)-kappaB was assayed
      with the immunohistochemical method. RESULTS: (1) In the control group, diarrhea
      and rectal bleeding recovered rapidly and no death was recorded. In the TNBS
      treated group, diarrhea and rectal bleeding persisted for a longer time. The
      mortality rate was 10.34% during the observation period. In the thalidomide
      treatment group, diarrhea and rectal bleeding persisted for a significantly
      shorter time than the TNBS-treated group (P < 0.01). The rats of this group also
      exhibited faster weight gain on day 7 compared with the TNBS-treated group but
      still lower than that of the control group. The mortality rate of the thalidomide
      treatment group was 3.57%. (2) Macroscopic and microscopic scores of the
      thalidomide-treated group were significantly lower than those of the TNBS model
      group on the 14th day (P < 0.01). These results suggested faster and better
      colonic recovery in the thalidomide-treated group. (3) NF-kappaB expression in
      the colonic mucosa of the control group was lower than in the others, mainly
      distributed in the cytoplasm. A large amount of intra-nuclear and cytoplasm
      staining was observed (more prominently intra-nuclear) in the TNBS model group
      and the thalidomide treatment group. On the 7th and 14th days, intra-nuclear NF
      kappaB-containing cells in the thalidomide treatment group were still
      significantly lower than those in the TNBS model group (P < 0.01). (4) In the
      control group, the cellular inflammatory factors (TNF-alpha, IL-1beta, and IL-10)
      were expressed at a low level while in the other two groups they were already
      expressed at a significantly higher level on day 4. On day 7 the expressions of
      TNF-alpha and IL-1beta in the thalidomide treatment group were lower than in the
      TNBS model group. On day 14, the expressions of TNF-alpha and IL-1beta in the
      thalidomide treatment group were significantly lower than in the TNBS model group
      (P < 0.05). On day 4, the IL-10 levels of the thalidomide treatment group became
      significantly elevated. The levels gradually decreased but still remained at a
      higher level. In the TNBS model group, the IL-10 expression peaked later than in
      the thalidomide treatment group. CONCLUSIONS: Thalidomide was effective in the
      management of TNBS-induced colitis in young rats. This may be due to the
      suppression and down-regulation of NF-kappaB and the expression of the downstream
      inflammatory mediators (TNF-alpha and IL-1beta). There is also indication that
      the expression of the anti-inflammatory cytokine (IL-10) is concomitantly up
      regulated as well.

PMID- 24931259
TI  - Effects of tacrolimus and cyclosporine treatment on metabolic syndrome and
      cardiovascular risk factors after renal transplantation: a meta-analysis.
AB  - BACKGROUND: The therapeutic success of renal transplantation has been largely
      attributable to the development of effective and balanced immunosuppressive
      treatment regimens. This study provides a meta-analysis of a series of randomized
      controlled trials that compared the effects of tacrolimus and cyclosporine on
      metabolic syndrome (MetS) and cardiovascular risk factors after renal
      transplantation. METHODS: We searched various electronic databases and
      bibliographies, including MEDLINE, the Cochrane Central Register of Controlled
      Trials, and EMBASE, for relevant studies published prior to October 2012.
      RESULTS: Our meta-analysis included five randomized controlled trials that
      examined a total of 923 patients. The tacrolimus group and the cyclosporine group
      exhibited no significant differences in MetS incidence after renal
      transplantation; risk ratio (RR): 1.06, 95% confidence interval (CI): 0.73-1.55,
      P = 0.76. Cyclosporine treatment was associated with a higher incidence of
      hyperlipidemia (RR: 0.50, 95% CI: 0.39-0.64, P < 0.01). Although there were no
      statistically significant differences, cyclosporine treatment was associated with
      a higher incidence of hypertension (RR: 0.91, 95% CI: 0.83-1.00, P = 0.06) after
      renal transplantation compared to tacrolimus treatment, and tacrolimus treatment
      was associated with a higher incidence of diabetes after renal transplantation
      (RR: 1.79, 95% CI: 0.98-3.27, P = 0.06) compared to cyclosporine treatment.
      CONCLUSIONS: Compared to tacrolimus treatment, cyclosporine treatment was
      associated with a higher incidence of hyperlipidemia. Future large-scale studies
      are expected to be conducted to further confirm our findings.

PMID- 24931260
TI  - T8590C polymorphism of CYP4A11 is a risk factor for hypertension: a meta
      analysis.
AB  - BACKGROUND: T8590C polymorphism of CYP4A11 has been associated with hypertension,
      though with conflicting results. The aim of this study was to quantitatively
      summarize the evidence for CYP4A11 T8590C polymorphism and hypertension risk.
      METHODS: Electronic search of PubMed and the Chinese Biomedicine database was
      conducted to select studies. Case-control studies containing available genotype
      frequencies of T8590C were chosen, and odds ratio (OR) with 95% confidence
      interval (CI) was used to assess the strength of this association. RESULTS: Seven
      case-control studies, including 3 295 cases and 3 192 controls, were identified.
      The meta-analysis, stratified by ethnicity, showed that individuals with the C
      allele carriers (CC+CT) had increased risk of hypertension in over all (OR =
      1.184, 95% CI: 1.063-1.319, P = 0.002) and in others (OR = 1.217, 95% CI: 1.045
      1.419, P = 0.012). The results among Asians did not suggest an association (OR =
      1.152, 95% CI: 0.990-1.342, P = 0.068). A symmetric funnel plot, the Egger's test
      (P = 0.863), and the Begg test (P = 0.393) were all suggestive of the lack of
      publication bias. CONCLUSIONS: This meta-analysis suggests the CYP4A11 T8590C
      polymorphism may be a risk factor for hypertension. Future well-designed large
      studies might be necessary to validate this association in different populations
      incorporated with environmental factors in the susceptibility of hypertension.

PMID- 24931261
TI  - Microarray-based analyses of monocytes from Chinese Uygur patients with
      Parkinson's disease and cognitive impairment.

PMID- 24931262
TI  - Serum levels of suppressor of cytokine signaling 3 and signal transducer and
      activator of transcription 3 in childhood atopic dermatitis.

PMID- 24931263
TI  - Pityriasis rubra pilaris (PRP) with preceding Epstein-Barr virus infection: a new
      type PRP with non-HIV virus infection?

PMID- 24931265
TI  - Two episodes of anaphylaxis caused by a chlorhexidine sulfadiazine-coated central
      venous catheter.

PMID- 24931264
TI  - Coronary artery anomalies: the left main coronary artery or left anterior
      descending coronary artery originating from the proximal of right coronary
      artery.

PMID- 24931266
TI  - Aortic reoperation in a patient with Loeys-Dietz syndrome.

PMID- 24931267
TI  - Frameless stereotactic aspiration and thrombolysis of moderate thalamic
      hemorrhage.

PMID- 24931268
TI  - The role of functional polymorphisms in immune response genes as biomarkers of
      bacille Calmette-Guerin (BCG) immunotherapy outcome in bladder cancer:
      establishment of a predictive profile in a Southern Europe population.
AB  - OBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the
      context of bacille Calmette-Guerin (BCG) immunotherapy outcome and create a
      predictive profile that may allow discrimination of the risk of recurrence.
      PATIENTS AND METHODS: In a dataset of 204 patients treated with BCG, we evaluated
      42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action,
      using Sequenom MassARRAY((r)) technology. Stepwise multivariate Cox regression
      was used for data mining. RESULTS: In agreement with previous studies we found
      that gender, age, tumour multiplicity and treatment scheme were associated with
      BCG failure. Using stepwise multivariate Cox regression analysis we propose the
      first predictive profile of BCG immunotherapy outcome and a risk score based on
      polymorphisms in immune system molecules [single nucleotide polymorphisms in
      tumour necrosis factor alpha (TNFA)-1031T/C (rs1799964), interleukin 2 receptor
      alpha (IL2RA) rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554),
      IL18R1 rs3771171 T/C, intercellular adhesion molecule 1 (ICAM-1) K469E (rs5498),
      Fas ligand (FASL)-844T/C (rs763110) and TNF-related apoptosis-inducing ligand
      receptor 1 (TRAILR1)-397T/G (rs79037040)] in association with clinicopathological
      variables. This risk score allows the categorisation of patients into risk
      groups: patients within the low-risk group have a 90% chance of successful
      treatment, whereas patients in the high-risk group present a 75% chance of
      recurrence after BCG treatment. CONCLUSION: We have established the first
      predictive score of BCG immunotherapy outcome combining clinicopathological
      characteristics and a panel of genetic polymorphisms. Further studies using an
      independent cohort are warranted. Moreover, the inclusion of other biomarkers may
      help to improve the proposed model.

PMID- 24931269
TI  - High-risk prostate cancer: a disease of genomic instability.
AB  - OBJECTIVES: In this review, we will discuss the latest advances in our
      understanding of the relationship between the cellular DNA damage response and
      genomic instability in prostate cancer and the emerging possibilities to exploit
      these aberrations as prognostic biomarkers and guides for personalized patient
      management. METHODS: Important findings related to genomic instability in
      prostate cancer were retrieved from the literature and combined with our own
      results and a translational perspective. RESULTS: Prostate cancer is
      characterized by a highly altered genomic landscape with a wide spectrum of
      genomic alterations, including somatic mutations, copy number alterations (CNAs),
      gene fusions, complex chromosomal rearrangements, and aneuploidy. In addition,
      massive DNA damaging events, including chromothripsis and chromoplexy, which can
      lead to extensive genomic insults in a single step, have been identified. A
      number of these genomic aberrations have been found to provide prognostic
      information and can therefore help to identify high-risk patients. In addition,
      defects in the DNA damage checkpoint and repair machinery can potentially be
      harnessed for therapeutic purposes. CONCLUSIONS: Genomic instability plays a
      crucial role in the malignant progression of prostate cancer and can be exploited
      for the development of novel prognostic biomarkers and innovative therapies.

PMID- 24931270
TI  - Micropapillary bladder cancer: current treatment patterns and review of the
      literature.
AB  - OBJECTIVES: No guidelines exist for the management of micropapillary bladder
      cancer (MPBC) and most reports of this variant of urothelial carcinoma are case
      series comprising small numbers of patients. We sought to determine current
      practice patterns for MPBC using a survey sent to the Society of Urologic
      Oncology (SUO) and to present those results in the setting of a comprehensive
      review of the existing literature. MATERIALS AND METHODS: A survey developed by
      the Translational Science Working Group of the Bladder Cancer Advocacy Network
      sponsored Think Tank meeting was distributed to members of the SUO. The results
      from 118 respondents were analyzed and presented with a literature review.
      RESULTS: Most survey respondents were urologists, with 80% considering bladder
      cancer their primary area of interest. Although 78% of the respondents reported a
      dedicated genitourinary pathologist at their institution, there were discrepant
      opinions on how a pathologic diagnosis of MPBC is determined as well as
      variability on the proportion of MPBC that is clinically significant. Among them,
      78% treat MPBC differently than conventional urothelial carcinoma, with 81%
      reporting that they would treat cT1 MPBC with upfront radical cystectomy.
      However, the respondents had split opinions regarding the sensitivity of MPBC to
      cisplatin-based chemotherapy, which affected utilization of neoadjuvant
      chemotherapy in muscle-invasive disease. CONCLUSIONS: The management of MPBC is
      diverse among members of the SUO. Although most favors early cystectomy for cT1
      MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle
      invasive MPBC.

PMID- 24931272
TI  - Chiral analysis of amino acid neurotransmitters and neuromodulators in mouse
      brain by CE-LIF.
AB  - Chiral CE method has been developed for quantitative determination of d-amino
      acid modulators of NMDA glutamate receptor; d-serine and d-aspartate along with l
      glutamate and l-aspartate in biological samples. These ligands are suggested to
      be involved in regulation of NMDA receptor related brain functions, such as
      neurogenesis, neuronal plasticity, and memory formation. For sensitive
      determination of the amino acids LIF detection was chosen, and a fluorogenic
      reagent, 7-fluoro-4-nitro-2,1,3-benzoxadiazole was used for derivatization. An
      amino-modified beta-CD, 6-monodeoxy-6-mono(3-hydroxy)propylamino-beta-CD (HPA
      beta-CD) was applied as chiral selector. Determinations were accomplished in a
      polyacrylamide coated capillary and reverse polarity was used for the analysis of
      the negatively charged analytes. The method was optimized and validated; 6 mM HPA
      beta-CD in 50 mM HEPES buffer, pH 7 was appropriate to achieve baseline
      separation of the analytes. The limit of quantification with acceptable accuracy
      is 0.05 MUM for both d-amino acids. The method was used for the determination of
      d-aspartate and d-serine content in various brain regions of adult mice. 

PMID- 24931271
TI  - Amyotrophic lateral sclerosis: impact of pulmonary follow-up and mechanical
      ventilation on survival. A study of 114 cases.
AB  - OBJECTIVE: To study the impact of ventilatory management and treatment on the
      survival of patients with amyotrophic lateral sclerosis (ALS). METHOD:
      Retrospective analysis of 114 consecutive patients admitted to a general
      hospital, evaluating demographic data, type of presentation, clinical management,
      treatment with mechanical ventilation and survival. STATISTICS: descriptive and
      Kaplan-Meier estimator. RESULTS: Sixty four patients presented initial bulbar
      involvement. Overall mean survival after diagnosis was 28.0 months (95%CI, 21.1
      34.8). Seventy patients were referred to the pulmonary specialist (61.4%) and 43
      received non-invasive ventilation (NIV) at 12.7 months (median) after diagnosis.
      Thirty seven patients continued to receive NIV with no subsequent invasive
      ventilation. The mean survival of these patients was 23.3 months (95%CI, 16.7
      28.8), higher in those without bulbar involvement, although below the range of
      significance. Survival in the 26 patients receiving programmed NIV was higher
      than in the 11 patients in whom this was indicated without prior pulmonary
      assessment (considered following diagnosis, P<.012, and in accordance with the
      start of ventilation, P<.004). A total of 7 patients were treated invasively;
      mean survival in this group was 72 months (95%CI, 14.36-129.6), median 49.6+/
      17.5 (95%CI, 15.3-83.8), and despite the difficulties involved in home care,
      acceptance and tolerance was acceptable. CONCLUSIONS: Long-term mechanical
      ventilation prolongs survival in ALS. Programmed pulmonary assessment has a
      positive impact on survival of ALS patients and is key to the multidisciplinary
      management of this disease.

PMID- 24931273
TI  - Chemical modifications of DNA for study of helicase mechanisms.
AB  - Helicases are ubiquitous enzymes that are required for virtually all processes in
      DNA and RNA metabolism including replication, repair, recombination,
      transcription, and translation. The mechanisms for helicase-catalyzed unwinding
      of double-stranded DNA or remodeling of RNA have been the subject of intense
      investigation for more than two decades. The central function of these enzymes is
      to transduce the energy available from ATP binding and hydrolysis to alter the
      conformation of nucleic acids. Specific interactions between helicases and
      nucleic acids have been investigated by chemical approaches in which the nucleic
      acid substrate has been modified in order to provide specific insight into the
      enzymatic mechanism. 

PMID- 24931274
TI  - Synthesis and biological evaluation of novel radioiodinated imidazopyridine
      derivatives for amyloid-beta imaging in Alzheimer's disease.
AB  - Non-invasive detection for amyloid-beta peptide (Abeta) deposition has important
      significance for the early diagnosis and medical intervention for Alzheimer's
      disease (AD). In this study, we developed a series of imidazopyridine derivatives
      as potential imaging agents for single-photon emission computed tomography
      (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for
      synthetic human Abeta 1-40 fibrils than did the well-known amyloid-imaging agent
      IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of
      (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled
      DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography
      clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region
      of AD enriched with Abeta plaques. Thus, our results strongly suggested that
      compound DRM106 can be used as an imaging agent for SPECT to detect Abeta
      deposition in AD brain. 

PMID- 24931276
TI  - Spectroscopic investigations of the binding mechanisms between antimicrobial
      peptides and membrane models of Pseudomonas aeruginosa and Klebsiella pneumoniae.
AB  - CD spectroscopy was used to investigate the interactions of a series of synthetic
      AMPs with LPS isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae, as
      well as with various phospholipids to better approximate the chemical composition
      of the membranes of these two strains of Gram-negative bacteria. This
      investigation was conducted in order to probe how the contributions of key
      physicochemical properties of an AMP vary in different regions of the membranes
      of these two bacteria. The conclusions from this study are as follows. (1) The
      binding interactions between the AMP and the membranes are defined by the
      complementarity of delocalization of positive charge density of the basic amino
      side chains (i.e., electrostatics), molecular flexibility of the peptide
      backbone, and overall hydrophobicity. (2) The binding interactions of these AMPs
      to LPS seem to be predominantly with the lipid A region of the LPS. (3)
      Incorporation of phospholipids into the LPS containing SUVs resulted in dramatic
      changes in the conformational equilibrium of the bound AMPs. (4) For the LPS
      phospholipid models of Pseudomonas aeruginosa, delocalization of the side chain
      positive charge plays a major role in determining the number of conformers that
      contribute to the binding conformational equilibrium. This relationship was not
      observed for the models of the outer and inner membranes of Klebsiella
      pneumoniae. 

PMID- 24931275
TI  - Synthesis and evaluation of N6-substituted apioadenosines as potential adenosine
      A3 receptor modulators.
AB  - Adenosine receptors (ARs) trigger signal transduction pathways inside the cell
      when activated by extracellular adenosine. Selective modulation of the A3AR
      subtype may be beneficial in controlling diseases such as colorectal cancer and
      rheumatoid arthritis. Here, we report the synthesis and evaluation of beta-D-apio
      D-furano- and alpha-D-apio-L-furanoadenosines and derivatives thereof.
      Introduction of a 2-methoxy-5-chlorobenzyl group at N(6) of beta-D-apio-D
      furanoadenosine afforded an A3AR antagonist (10c, Ki=0.98 MUM), while a similar
      modification of an alpha-D-apio-L-furanoadenosine gave rise to a partial agonist
      (11c, Ki=3.07 MUM). The structural basis for this difference was examined by
      docking to an A3AR model; the antagonist lacked a crucial interaction with Thr94.

PMID- 24931277
TI  - Topoisomerase II inhibitors from the roots of Stellera chamaejasme L.
AB  - Three new compounds, including one daphnane diterpene (1), one sesquiterpene (6),
      and one lignan (7) have been isolated from the Stellera chamaejasme L., together
      with five other known compounds, including four daphnane diterpenenoids (2-5) and
      one lignan (8). The structures of the new compounds were elucidated by
      spectroscopic analysis. The cytotoxicities of compounds 1-8 towards human lung
      adenocarcinoma cells (A549 cells) were evaluated using a sulforhodamine B assay.
      All of the compounds displayed significant cytotoxicity, with IC50 values in the
      ranging of 0.2 nM to 2.0 MUM. Mechanistic studies revealed that the antitumor
      activities of compounds 1-3 and 7 were derived from their inhibition of
      topoisomerase II (Topo II). Furthermore, as a Topo II inhibitor, compound 1 was
      found to effectively induced G2-M phase cell cycle arrest and apoptosis in cancer
      cells.

PMID- 24931278
TI  - Review article: Emergency department data sharing to reduce alcohol-related
      violence: a systematic review of the feasibility and effectiveness of community
      level interventions.
AB  - The present paper aims to review current evidence for the effectiveness and/or
      feasibility of using inter-agency data sharing of ED recorded assault information
      to direct interventions reducing alcohol-related or nightlife assaults, injury or
      violence. Potential data-sharing partners involve police, local council, liquor
      licensing regulators and venue management. A systematic review of the peer
      reviewed literature was conducted. The initial search discovered 19,506 articles.
      After removal of duplicates and articles not meeting review criteria, n = 8
      articles were included in quantitative and narrative synthesis. Seven of eight
      studies were conducted in UK EDs, with the remaining study presenting Australian
      data. All studies included in the review deemed data sharing a worthwhile
      pursuit. All studies attempting to measure intervention effectiveness reported
      substantial reductions of assaults and ED attendances post-intervention, with one
      reporting no change. Negative logistic feasibility concerns were minimal, with
      general consensus among authors being that data-sharing protocols and
      partnerships could be easily implemented into modern ED triage systems, with
      minimal cost, staff workload burden, impact to patient safety, service and
      anonymity, or risk of harm displacement to other licensed venues, or increase to
      length of patient stay. However, one study reported a potential harm displacement
      effect to streets surrounding intervention venues. In future, data-sharing
      systems should triangulate ED, police and ambulance data sources, and assess
      intervention effectiveness using randomised controlled trials that account for
      variations in venue capacity, fluctuations in ED attendance and population
      levels, seasonal variations in assault and injury, and control for concurrent
      interventions.

PMID- 24931279
TI  - A semimetal bismuth element as a direct plasmonic photocatalyst.
AB  - The bismuth element synthesized by a facile chemical solution method exhibited an
      admirable and stable photocatalytic activity towards the removal of NO under 280
      nm light irradiation due to the surface plasmon resonance mediated direct
      photocatalysis, and most strikingly, showed a catalytic "memory" capability
      following illumination. 

PMID- 24931280
TI  - The effect of Mediterranean diet on the development of type 2 diabetes mellitus:
      a meta-analysis of 10 prospective studies and 136,846 participants.
AB  - OBJECTIVE: The purpose of this work was to meta-analyze prospective studies that
      have evaluated the effect of a Mediterranean diet on the development of type 2
      diabetes. MATERIALS/METHODS: PubMed, Embase and the Cochrane Central Register of
      Controlled Trials databases were searched up to 20 November 2013. English
      language publications were allocated; 17 original research studies (1 clinical
      trial, 9 prospective and 7 cross-sectional) were identified. Primary analyses
      were limited to prospective studies and clinical trials, yielding to a sample of
      136,846 participants. A systematic review and a random effects meta-analysis were
      conducted. RESULTS: Higher adherence to the Mediterranean diet was associated
      with 23% reduced risk of developing type 2 diabetes (combined relative risk for
      upper versus lowest available centile: 0.77; 95% CI: 0.66, 0.89). Subgroup
      analyses based on region, health status of participants and number of confounders
      controlling for, showed similar results. Limitations include variations in
      Mediterranean diet adherence assessment tools, confounders' adjustment, duration
      of follow up and number of events with diabetes. CONCLUSIONS: The presented
      results are of major public health importance, since no consensus exists
      concerning the best anti-diabetic diet. Mediterranean diet could, if
      appropriately adjusted to reflect local food availability and individual's needs,
      constitute a beneficial nutritional choice for the primary prevention of
      diabetes.

PMID- 24931282
TI  - Pediatric transplantation and tolerance: past, present, and future.
AB  - Solid organ transplantation is the treatment of choice in children with end-stage
      organ failure. With improving methods of transplant surgery and post-transplant
      care, transplantation is more frequently performed worldwide. However, lifelong
      and non-specific suppression of the recipient's immune system is a cause of
      significant morbidity in children, including infection, diabetes, and cancer.
      There is a great need to develop IS minimization/withdrawal and tolerance
      induction approaches. 

PMID- 24931283
TI  - A novel technique to improve the diagnostic yield of negative sestamibi scans.
AB  - INTRODUCTION: Minimally invasive parathyroidectomy is successful in achieving
      cure for most patients with primary hyperparathyroidism. Most surgeons rely on
      preoperative imaging as part of the workup for localization. Ultrasonography and
      sestamibi are the 2 most commonly used preoperative imaging studies. When these 2
      studies are positive and concordant the preoperative localization is
      straightforward. However, when >=1 of these studies is negative, the preoperative
      localization is suspect. We hypothesize that the yield of useful localizing
      information from "negative" sestamibi scans can be increased in certain
      situations. Specifically, in cases where the thyroid lobe length seen on
      sestamibi is discordant from the lobe length of the ultrasonography, this often
      represents a "hidden" parathyroid adenoma. If our hypothesis is correct, this
      could lead to decreased resource utilization in cases of nonlocalized parathyroid
      adenomas. METHODS: We retrospectively analyzed our database of patients with
      primary hyperparathyroidism who underwent parathyroidectomy from 2005 to 2011.
      The anteroposterior views of early phase sestamibi were analyzed for thyroid lobe
      lengths. A ratio of the length of the right lobe to left lobe was calculated. The
      thyroid lobe lengths on ultrasonography were measured and similar ratios were
      calculated. The difference in ratios between sestamibi and ultrasonography was
      calculated for each patient. A difference in ratios from sestamibi and
      ultrasonography that corresponded with a "hidden" parathyroid on the side of the
      additional length on sestamibi at the time of surgery was considered a positive
      finding. When the difference in ratios from the 2 images did not correspond with
      a "hidden" parathyroid at the time of operation, it was considered a negative
      finding. RESULTS: There were 59 patients with single-gland disease, negative
      sestamibi, and images available for review. There were 32 patients (54%) with the
      positive finding of a "hidden" parathyroid corresponding with a difference in
      thyroid lobe length ratios from sestamibi and ultrasonography. The overall mean
      difference in ratios between sestamibi and ultrasonography was 0.37 +/- 0.32. The
      mean ratio difference in the group of patients with a negative "hidden"
      parathyroid was 0.11 +/- 0.02, and the mean ratio difference in the group of
      patients with a positive "hidden" parathyroid was 0.58 +/- 0.05 (P < .001). When
      a difference in ratios of >=0.23 was obtained, this predicted a "hidden"
      parathyroid with a sensitivity of 93.8% and specificity of 85.2%. There were 39
      patients with multigland disease, negative sestamibi, and images available for
      review. None of these patients had a ratio difference of >=0.23. The mean ratio
      difference for patients with multigland disease was significantly lower than that
      of the single-gland disease (0.08 +/- 0.06 vs 0.37 +/- 0.32; P < .001).
      CONCLUSION: Discordance between thyroid lobe lengths on the early phase sestamibi
      compared with ultrasonography has led to successful preoperative identification
      of parathyroid adenomas, even though the sestamibi was traditionally read as
      negative. This finding has not been previously described, seems to be reliable,
      and can lead to improved preoperative localization and decreased resource
      utilization in this subset patients.

PMID- 24931281
TI  - Lactation intensity and fasting plasma lipids, lipoproteins, non-esterified free
      fatty acids, leptin and adiponectin in postpartum women with recent gestational
      diabetes mellitus: the SWIFT cohort.
AB  - OBJECTIVES: Lactation may influence future progression to type 2 diabetes after
      gestational diabetes mellitus (GDM). However, biomarkers associated with
      progression to glucose intolerance have not been examined in relation to
      lactation intensity among postpartum women with previous GDM. This study
      investigates whether higher lactation intensity is related to more favorable
      blood lipids, lipoproteins and adipokines after GDM pregnancy independent of
      obesity, socio-demographics and insulin resistance. METHODS: The Study of Women,
      Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that
      recruited 1035 women diagnosed with GDM by the 3-h 100g oral glucose tolerance
      tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff
      conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry,
      lifestyle behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We
      assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids,
      leptin and adiponectin from stored samples obtained at 6-9 weeks postpartum in
      1007 of the SWIFT participants who were free of diabetes at baseline. Mean
      biomarker concentrations were compared among lactation intensity groups using
      multivariable linear regression models. RESULTS: Increasing lactation intensity
      showed graded monotonic associations with fully adjusted mean biomarkers: 5%-8%
      higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%-28% lower
      fasting triglycerides, 15%-21% lower leptin (all trend P-values < 0.01), and with
      6% lower adiponectin, but only after adjustment for insulin resistance (trend P
      value = 0.04). CONCLUSION: Higher lactation intensity was associated with more
      favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin,
      after GDM delivery. Long-term follow-up studies are needed to assess whether
      these effects of lactation persist to predict progression to glucose intolerance.

PMID- 24931284
TI  - Physa marmorata (Mollusca: Physidae) as a natural intermediate host of
      Trichobilharzia (Trematoda: Schistosomatidae), a potential causative agent of
      avian cercarial dermatitis in Brazil.
AB  - Species of Trichobilharzia are the main etiological agents of cercarial
      dermatitis in humans, which is considered a re-emerging disease. Despite the
      diversity and global distribution of species of this genus, studies of
      Trichobilharzia are scarce in South America. The goal of our investigations is
      better understand the diversity, distribution and life cycle of avian
      schistosomes and their likely role in causing dermatitis in Brazil. As part of
      this effort, cercariae found in naturally infected Physa marmorata were
      identified by morphological and molecular (mitochondrial cox1, nuclear ITS1 and
      28S gene regions) methods as Trichobilharzia sp. These cercariae are similar
      morphologically to T. jequitibaensis described previously from Brazil and similar
      genetically to the North American physid transmitted species T. querquedulae and
      T. physellae. This is the first report of a potential agent of cercarial
      dermatitis from naturally infected snails from Brazil and first molecular
      characterization of a South American species of Trichobilharzia. A discussion
      follows concerning the potential role of this species has in outbreaks of
      dermatitis in Brazil. 

PMID- 24931285
TI  - Equine trypanosomosis in central and western Punjab: prevalence, haemato
      biochemical response and associated risk factors.
AB  - The detection of Trypanosoma evansi in blood is intricate, primarily in chronic
      stage of infection, as the parasitaemia is often low and fluctuating. The
      climatic conditions of the target area of Punjab (a province of India with a
      total of 34,000 horses and ponies used for sports and transport) are conducive
      for the parasite propagation. The objective of present investigation was to
      assess the prevalence of T. evansi in central and western Punjab by PCR and card
      agglutination test (CATT/T. evansi) in relation to clinico-haematobiochemical
      alterations and risk factors associated with latent trypanosomosis. A total of
      169 equine blood and serum samples tested by CATT/T. evansi revealed 16 cases
      positive, with 6.8% from central plain and 13.63% from western zone. To assess
      the specificity of serological test, PCR1 was performed using established primer
      pair TR3 5'-GCG CGG ATT CTT TGC AGA CGA-3' and TR4 5'-TGC AGA CAC TGG AAT GTT ACT
      3' for T. evansi. PCR2 applied with primer pair RoTat1.2F: 5'-ATG TCA ACG ATG CCT
      GTT ACA TTA CGC AC-3' and RoTat1.2R: 5'-TAA ATA TCA CTG TCA AGA CCT GCT GCG G-3'
      to rule out the consensus between the finding of the two PCR assays and
      agglutination test for T. evansi, which displayed results in concordance with
      PCR1. PCR assays showed 1.92 and 1.51% positive samples from central plain and
      western zone, respectively. With respect to PCR assay, CATT/T. evansi showed 100%
      sensitivity and 92.1% specificity. Microscopy showed a very low prevalence rate
      of 0.59% with only one sample positive with teaming parasitaemia. Comparison
      between sexes revealed higher positivity in mares by the three tests (BSE: 0.95%,
      PCR: 2.88%, CATT/T. evansi: 14.42%). The haemato-biochemical factors were found
      to be altered in PCR positive cases, while the mean value of vital parameters
      lied in normal range in seropositive cases. The female horse (RR=0.0937, 95%
      CI=1.388-190.223%) population was found to be at the highest risk of
      seropositivity for T. evansi, particularly in the unorganized farms (RR=19.726,
      95% CI=2.918-400.221%). 

PMID- 24931286
TI  - Necrosis targeted combinational theragnostic approach using radioiodinated
      Sennidin A in rodent tumor models.
AB  - Residual cancer cells and subsequent tumor relapse is an obstacle for curative
      cancer treatment. Tumor necrosis therapy (TNT) has recently been developed to
      cause residual tumor regression or destruction. Here, we exploited the avidity of
      the sennidin A (SA) tracer and radioiodinated SA (131I-SA) to necrotic tumors in
      order to further empower TNT. We showed high uptake and prolonged retention of SA
      in necrotic tumors and a quick clearance in other non-targeted tissues including
      the liver. On SPECT-CT images, tumor mass appeared persistently as a hotspot.
      Based on the prominent targetability of 131I-SA to the tumor necrosis, we
      designed a combinational theragnostic modality. The vascular disrupting agent
      (VDA) combretastatin A4 phosphate (CA4P) was used to cause massive tumor
      necrosis, which formed the target of 131I-SA that subsequently killed the
      residual tumor cells by cross-fire irradiation of beta particles. Consequently,
      131I-SA combined with CA4P significantly inhibited tumor growth, extended tumor
      doubling time and prolonged mean animal survival. In conclusion, 131I-SA in
      combination with necrosis inducing drugs/therapies may generate synergetic
      tumoricidal effects on solid malignancies by means of primary debulking and
      secondary cleansing process.

PMID- 24931288
TI  - A structured, parsimonious approach to establish the cause of moderate-to-large
      pericardial effusion.
AB  - The workup of moderate-to-large pericardial effusion should focus on its
      hemodynamic impact and potential cause. A structured approach to diagnostic
      evaluation of pericardial effusion is needed. We retrospectively studied a
      contemporary cohort of 103 patients with moderate-to-large pericardial effusion
      hospitalized at St. Luke's Roosevelt Hospital Center from July 2009 till August
      2013. Diagnosis of pericardial effusion was independently ascertained by chart
      review. We applied a stepwise parsimonious approach to establish the cause of
      pericardial effusion. In the studied cohort, the mean age was 61 years, 50% were
      men, and 65 patients (63%) underwent pericardial effusion drainage. Using the
      structured approach, the cause of the effusion was ascertained in 70 patients
      (68%) by noninvasive targeted testing. Malignant effusion was confirmed in 19
      patients (19%). All patients with malignant effusion had either history of
      malignancy or suggestive noninvasive findings. In conclusion, a structured
      approach can help to ascertain the diagnosis in patients with moderate-to-large
      pericardial effusion and guide the need for pericardial drainage or sampling. 

PMID- 24931287
TI  - Factors influencing the attitudes of Chinese cancer patients and their families
      toward the disclosure of a cancer diagnosis.
AB  - The disclosure of a cancer diagnosis to patients has been a core topic in
      oncology departments. Previous studies have demonstrated that Chinese cancer
      patients and their families differ in their attitudes toward cancer diagnosis
      disclosure. However, the influencing factors regarding their different attitudes
      remain unknown. In the present study, a questionnaire was delivered to 266 cancer
      patients and 266 matched family members. The results showed that cancer patients
      were more likely to desire to be informed of their condition than family members
      (85 vs. 18%, P < 0.01). The patients' age had a significant influence on their
      attitudes (P < 0.01), while the family members' gender, profession, educational
      level, and their relationship with the patients could significantly affect their
      attitudes (all P < 0.05). Further multivariate analyses indicated that a family
      member's gender (odds ratio (OR) = 2.928, 95% confidence interval (CI) 1.379
      6.213, P = 0.005), profession (OR = 2.814, 95% CI 1.548-5.119, P = 0.001), and
      educational level (OR = 0.105, 95% CI 0.053-0.211, P < 0.001) remained
      significant variables. Due to a lower educational level, only 74% of families
      knew about chemotherapy, and 90% of families were not familiar with molecular
      targeted therapy. However, 78% of patients expected to be cured of their cancer,
      16.5% expected to reduce the severity of their condition, and 4.9% expected to
      lengthen their lives. Therefore, physicians have a responsibility to
      appropriately provide knowledge regarding cancer to the patients' families if
      their educational level is lower and if they have no knowledge of recent
      treatments, which may improve their acceptability of a cancer diagnosis for
      patients.

PMID- 24931289
TI  - Frequency of depression and anxiety before and after insertion of a continuous
      flow left ventricular assist device.
AB  - Our objective was to investigate the course of depression and anxiety symptoms in
      patients treated with continuous flow (CF) left ventricular assist devices
      (LVADs). Depression and anxiety are associated with poor outcomes in patients
      with heart failure, yet few studies have examined such symptoms in patients with
      CF-LVADs. Depression and anxiety were measured as part of routine clinical care
      in patients who received a CF-LVAD at our institution from October 2009 to April
      2012. Sixty-six patients completed the Patient Health Questionnaire-9, and 48 of
      66 patients also completed the Generalized Anxiety Disorder Questionnaire-7.
      Nineteen of 66 patients completed measures before implantation. Patients who
      completed measures before and after implantation demonstrated significant
      improvements in depression and anxiety scores. All patients showed significant
      improvements in depression and anxiety scores from implantation to the first time
      point after implantation. Pairwise mean comparisons between time intervals after
      implantation were not significant. In conclusion, depression and anxiety scores
      improve after CF-LVAD implantation and remain stable up to 1 year. The
      improvement does not depend on baseline psychotropic medication use and may be
      related to improved physical health. 

PMID- 24931290
TI  - Prevalence of arrhythmias during exercise stress testing in patients with
      congenital heart disease and severe right ventricular conduit dysfunction.
AB  - The utility of cardiopulmonary exercise testing (CPET) to define the risks of
      arrhythmia and sudden death in postoperative patients with congenital heart
      disease (CHD) remains uncertain. As part of the US Melody valve trial,
      prospective standardized CPET, along with echocardiography, cardiac magnetic
      resonance imaging, and cardiac catheterization, were performed in 170 CHD
      patients with right ventricular outflow tract conduit dysfunction before Melody
      valve implantation. Ventricular premature complexes (VPC) occurred in 75 patients
      (44%) and were common during all phases of CPET (13% baseline, 24% exercise, and
      23% recovery). Although no subjects had sustained arrhythmias, 2 had nonsustained
      ventricular tachycardia and 3 had nonsustained supraventricular tachycardia
      during recovery. There were no statistically significant differences between
      patients with or without VPCs in echocardiographic, cardiac magnetic resonance
      imaging, or catheterization measures of cardiac function. However, clinical
      parameters of age, New York Heart Association functional class >=II, and >=3
      cardiac surgical procedures were correlated with VPCs. Persistent ventricular
      ectopy during all exercise stages was present in 11 patients (6.5%), including 3
      of the 4 patients who died during follow-up. In conclusion, VPCs were common
      during CPET, although they were not correlated with various measures of
      hemodynamic impairment; conversely, increased age, functional class, and number
      of surgeries were correlated with an increased prevalence of VPCs. CPET appears
      to be of minimal risk for sustained arrhythmia provocation in CHD patients with
      right ventricular outflow tract conduits and various degrees of advanced
      subpulmonary ventricular dysfunction. 

PMID- 24931291
TI  - Relation of C-reactive protein levels to instability of untreated vulnerable
      coronary plaques (from the PROSPECT Study).
AB  - C-reactive protein (CRP) levels predict adverse coronary events, but it is
      uncertain if they predict the burden or stability of vulnerable coronary plaques.
      In the Providing Regional Observations to Study Predictors of Events in the
      Coronary Tree study, 697 patients with acute coronary syndromes underwent
      percutaneous coronary intervention followed by 3-vessel angiography, gray-scale
      intravascular ultrasound (IVUS), and radiofrequency IVUS. Major adverse cardiac
      events (MACE) during 3 years of follow-up were adjudicated to initially treated
      culprit lesions or to untreated nonculprit lesions (NCLs). NCLs at greatest risk
      of causing subsequent MACE had plaque burden >=70%, minimal luminal area <=4.0
      mm(2), and/or thin-cap fibroatheroma morphology. Here, we examine the interaction
      of high-risk NCLs with CRP levels, which were measured at presentation, 1 month,
      and 6 months, then categorized at each time as normal (<3 mg/L), elevated (3 to
      10 mg/L), or very elevated (>10 mg/L). We found that patients with elevated CRP
      levels at any time did not have more high-risk NCLs; however, untreated high-risk
      NCLs were more likely to cause subsequent MACE in patients with very elevated
      compared with normal 6-month CRP levels (for thin-cap fibroatheromas, 13.8% vs
      1.9%, p = 0.0003; for lesions with minimal luminal area <=4.0 mm(2), 15.6% vs
      2.2%, p <0.0001). As expected, patients with very elevated 6-month CRP levels had
      higher rates of subsequent NCL-related MACE (19.0% vs 7.2%, p = 0.039). In
      conclusion, the higher rates of NCL-related MACE in post-acute coronary syndrome
      patients with very elevated CRP levels may reflect greater instability of high
      risk NCLs, rather than a larger burden of such lesions. 

PMID- 24931292
TI  - Ischemic stroke occurring during intercourse in young women on oral
      contraceptives.
AB  - Ischemic stroke occurring during intercourse in young patients is exceedingly
      rare. We present 2 cases of young women taking oral contraceptives, each
      presenting with an ischemic stroke. Transthoracic echocardiography revealed a
      patent foramen ovale in one patient and an atrial septal defect in the other. The
      most likely cause of stroke in both patients is embolic. Despite conflicting
      evidence, young patients presenting with ischemic stroke and found to have a
      patent foramen ovale or atrial septal defect should be considered for possible
      device-based closure. 

PMID- 24931293
TI  - Comments on - vaginal dose point reporting in cervical cancer patients treated
      with combined 2D/3D external beam radiotherapy and 2D/3D brachytherapy.

PMID- 24931294
TI  - Toward a general ontology for digital forensic disciplines.
AB  - Ontologies are widely used in different disciplines as a technique for
      representing and reasoning about domain knowledge. However, despite the
      widespread ontology-related research activities and applications in different
      disciplines, the development of ontologies and ontology research activities is
      still wanting in digital forensics. This paper therefore presents the case for
      establishing an ontology for digital forensic disciplines. Such an ontology would
      enable better categorization of the digital forensic disciplines, as well as
      assist in the development of methodologies and specifications that can offer
      direction in different areas of digital forensics. This includes such areas as
      professional specialization, certifications, development of digital forensic
      tools, curricula, and educational materials. In addition, the ontology presented
      in this paper can be used, for example, to better organize the digital forensic
      domain knowledge and explicitly describe the discipline's semantics in a common
      way. Finally, this paper is meant to spark discussions and further research on an
      internationally agreed ontological distinction of the digital forensic
      disciplines. Digital forensic disciplines ontology is a novel approach toward
      organizing the digital forensic domain knowledge and constitutes the main
      contribution of this paper. 

PMID- 24931295
TI  - Evaluation of Florida physicians' knowledge and attitudes toward accessing the
      state prescription drug monitoring program as a prescribing tool.
AB  - OBJECTIVE: The purpose of this study is to assess Florida physicians' attitudes
      and knowledge toward accessing the state's prescription drug monitoring program
      (PDMP). DESIGN: Five thousand medical doctors and osteopathic physicians licensed
      in Florida were randomly selected for a voluntary and anonymous 15-question self
      administered survey approved by the Institutional Review Board. Surveys were
      distributed through U.S. postal service mail. Likert-scale questions were used to
      assess prior knowledge (1 = none to 5 = excellent) and attitudes toward accessing
      the PDMP (1 = strongly disagree to 5 = strongly agree). RESULTS: The study
      yielded a response rate of 7.8%, 71.5% of whom agreed or strongly agreed that the
      PDMP is a useful tool. Among participants that have access and answered the PDMP
      usefulness question, 94.8% agree or strongly agree that it is a useful tool.
      There were 63 out of 64 physicians (98.4%) who conducted 25 or more searches who
      agreed or strongly agreed that the PDMP is a useful tool for monitoring patients'
      controlled substance histories. There were 72.5% of participants with access that
      answered the "doctor shopping" question who agreed that "doctor shopping" will
      decrease. Among the 64 most frequent PDMP users, 69.4% agreed or strongly agreed
      that they have prescribed fewer controlled substances after accessing the PDMP.
      CONCLUSIONS: The study revealed that a majority of participants believe that the
      PDMP is a useful tool for monitoring patients' controlled substance histories.
      More continuing education programs should be provided to Florida physicians to
      enhance their knowledge regarding PDMPs.

PMID- 24931296
TI  - Effect of orexin A on the release of GnRH-stimulated gonadotrophins from cultured
      pituitary cells of immature and mature female rats.
AB  - Orexin A (OxA), also known as hypocretin 1, is a regulatory neuropeptide involved
      in the control of various autonomic and neuroendocrine functions. It appears to
      have a significant impact on the regulation of trophic hormones secretion by
      influencing the hypothalamus and the pituitary. Orexin A acts through two types
      of receptor found in the pituitary. This suggests the possibility of direct
      action of OxA at the adenohypophysis level. The aim of this study was to
      investigate the direct effect of OxA on GnRH (gonadotrophin-releasing hormone)
      stimulated LH and FSH secretion from cultured pituitary cells of sexually
      immature and mature female rats. Anterior pituitary cells obtained from immature
      and mature female rats (ovariectomized, and ovariectomized and treated with
      estradiol) were incubated with 10(-10)M or 10(-7)M orexin A for 1 hour and 4h and
      the effect on GnRH-stimulated (10(-9)M or 10(-6)M) LH and FSH release was
      examined. The concentrations of secreted gonadotrophins in the culture media were
      determined by RIA methods. Orexin A significantly inhibited GnRH-stimulated FSH
      release from pituitary cells isolated from immature female rats, whereas in cells
      of mature ovariectomized animals, the effect of OxA was dependent on the
      stimulatory dose of GnRH. When the cells were stimulated with a low dose of GnRH,
      orexin A inhibited the secretion of gonadotrophins, but when a high dose of GnRH
      was used, orexin A increased mainly the release of LH. In cultured pituitary
      cells from ovariectomized, estrogenized mature rats, orexin A inhibited the
      secretion of LH if the cells were stimulated with a high dose of GnRH. In
      conclusion, the results of this study revealed that orexin A may modify the
      sensitivity of gonadotrophic cells to GnRH, and its effect depends on the
      maturity and estrogen status of the rats from which the cells are isolated.

PMID- 24931297
TI  - Biochemical and clinical features of hereditary hyperprolinemia.
AB  - There are two classifications of hereditary hyperprolinemia: type I (HPI) and
      type II (HPII). Each type is caused by an autosomal recessive inborn error of the
      proline metabolic pathway. HPI is caused by an abnormality in the proline
      oxidizing enzyme (POX). HPII is caused by a deficiency of Delta-1-pyrroline-5
      carboxylate (P5C) dehydrogenase (P5CDh). The clinical features of HPI are
      unclear. Nephropathy, uncontrolled seizures, mental retardation or schizophrenia
      have been reported in HPI, but a benign phenotype without neurological problems
      has also been reported. The clinical features of HPII are also unclear. In
      addition, the precise incidences of HPI and HPII are unknown. Only two cases of
      HPI and one case of HPII have been identified in Japan through a questionnaire
      survey and by a study of previous reports. This suggests that hyperprolinemia is
      a very rare disease in Japan, consistent with earlier reports in Western
      countries. The one case of HPII found in Japan was diagnosed in an individual
      with influenza-associated encephalopathy. This suggests that HPII might reduce
      the threshold for convulsions, thereby increasing the sensitivity of individuals
      with influenza-associated encephalopathy. The current study presents diagnostic
      criteria for HPI and HPII, based on plasma proline level, with or without
      measurements of urinary P5C. In the future, screening for HPI and HPII in healthy
      individuals, or patients with relatively common diseases such as developmental
      disabilities, epilepsy, schizophrenia or behavioral problems will be important. 

PMID- 24931298
TI  - Characterisation of the antidepressant properties of nitric oxide synthase
      inhibitors in the olfactory bulbectomised rat model of depression.
AB  - Nitric oxide synthase (NOS) inhibitors possess antidepressant-like properties in
      preclinical tests and in the current investigation the brain penetrant NOS
      inhibitor N(omega)-nitro-L-arginine (l-NA) and the preferential inhibitor of
      neuronal NOS (nNOS) 1-(2-trifluoromethylphenyl) imidazole (TRIM) were assessed in
      the olfactory bulbectomised (OB) rat, a well-established animal model of
      depression. Magnetic resonance imaging (MRI) was employed to assess regional
      brain volumes, blood perfusion and T1 and T2 relaxometry times both with and
      without drug treatment. l-NA (10 mg/kg, once daily p.o. for 10 days) attenuated
      OB-related hyperactivity in the "open field" test in a comparable fashion to the
      tricyclic antidepressant imipramine (20 mg/kg, once daily p.o. for 14 days)
      indicative of an antidepressant-like response in the model. Treatment with TRIM
      (50 mg/kg, once daily s.c.) attenuated OB-related hyperactivity following 7 days
      of treatment when compared to vehicle treated controls. OB is associated with
      enlarged ventricular volume, increased periventicular perfusion and a decrease in
      T2 relaxation times in cortical and hippocampal regions, with enhanced perfusion
      and reduced T2 times attenuated by L-NA treatment. L-NA treatment was also
      associated with an increase in T1 relaxation times in limbic and cortical regions
      and found to reduce resting state hippocampal blood perfusion in OB animals.
      Behavioural observations are consistent with an antidepressant action of NOS
      inhibitors where associated changes in perfusion and T2 relaxation times may be
      related to the antidepressant action of L-NA in the model.

PMID- 24931299
TI  - Bos indicus introgression into (peri-)alpine cattle breeds - evidence from the
      analysis of bovine whey protein variants.
AB  - The major bovine whey proteins, alpha-lactalbumin (alpha-LA) and beta
      lactoglobulin (beta-LG), exhibit breed-specific genetic variation. The aim of
      this study was to identify possible new protein variants and determine the
      distribution of variants across a variety of 18 taurine and indicine cattle
      breeds applying a DNA-based sequencing approach. To this end, the open reading
      frames of the respective genes (LALBA and LGB) were sequenced in 476 animals.
      Within the LALBA gene, a previously unknown synonymous and a previously
      undesignated non-synonymous nucleotide exchange were identified. Furthermore, two
      known alpha-LA variants (A and B) and four known beta-LG variants (A, B, C and W)
      were determined. The occurrence of typical indicine variants in some taurine
      cattle breeds, such as Suisse Eringer, German Hinterwalder and Hungarian Grey
      Steppe, further supports the hypothesis of ancient Bos indicus introgression into
      (peri-)alpine cattle breeds. 

PMID- 24931300
TI  - The Health and Functioning ICF-60: development and psychometric properties.
AB  - BACKGROUND: This paper describes the development and psychometric properties of
      the Health and Functioning ICF-60 (HF-ICF-60) measure, based on the World Health
      Organization (WHO) 'International Classification of Functioning, Disability and
      Health: ICF' (2001). The aims of the present study were to test psychometric
      properties of the HF-ICF-60, developed as a measure that would be responsive to
      change in functioning through changes in health and nutritional status, as a
      prospective measure to monitor health and nutritional status of populations and
      to explore the relationship of the HF-ICF-60 with quality of life measures such
      as the World Health Organization WHOQOL-BREF quality of life assessment in
      relation to non-communicable diseases. METHODS: The HF-ICF-60 measure consists of
      60 items selected from the ICF by an expert panel, which included 18 items that
      cover Body Functions, 21 items that cover Activities and Participation, rated on
      five-point scales, and 21 items that cover Environmental Factors (seven items
      cover Individual Environmental Factors and 14 items cover Societal Environmental
      Factors), rated on nine-point scales. The HF-ICF-60 measure was administered to
      the Russian nationally representative sample within the Russian National
      Population Quality of Life, Health and Nutrition Survey, in 2004 (n = 9807) and
      2005 (n = 9560), as part of the two waves of the Russian Longitudinal Monitoring
      Survey (RLMS). The statistical analyses were carried out with the use of both
      classical and modern psychometric methods, such as factor analysis, and based on
      Item Response Theory, respectively. RESULTS: The HF-ICF-60 questionnaire is a new
      measure derived directly from the ICF and covers the ICF components as follows:
      Body Functions, Activities and Participation, and Environmental Factors
      (Individual Environmental Factors and Societal Environmental Factors). The
      results from the factor analyses (both Exploratory Factor Analyses and
      Confirmatory Factor Analyses) show good support for the proposed structure
      together with an overall higher-order factor for each scale of the measure. The
      measure has good reliability and validity, and sensitivity to change in the
      health and nutritional status of respondents over time. Normative values were
      developed for the Russian adult population. CONCLUSIONS: The HF-ICF-60 has shown
      good psychometric properties in the two waves of the nationally representative
      RLMS, which provided considerable support to using the HF-ICF-60 data as the
      normative health and functioning values for the Russian population. Similarly,
      the administration of the WHOQOL-BREF in the same two waves of the nationally
      representative RLMS has allowed the normative quality of life values for the
      Russian population to be obtained. Therefore, the objective assessment of health
      and functioning of the HF-ICF-60 could be mapped onto the subjective evaluation
      of quality of life of the WHOQOL-BREF to increase the potential usefulness of the
      surveys in relation to non-communicable diseases. KEY PRACTITIONER MESSAGE: The
      HF-ICF-60 offers a new perspective in measuring change in functioning through
      changes in lifestyle and diet. The HF-ICF-60 can be combined with the WHOQOL-BREF
      to map the objective assessment of health and functioning onto the subjective
      evaluation of quality of life. Combined use of the HF-ICF-60 and the WHOQOL-BREF
      can be especially useful for national and global monitoring and surveillance of
      implementation of measures to reduce risk factors of non-communicable diseases
      and to promote healthy lifestyles and healthy diets.

PMID- 24931302
TI  - Ageing populations and changing worlds of work.
AB  - Population ageing has reshaped the notion of retirement. The changes carry
      important implications for aspirations to extend working life. Cultural
      expectations regarding work and retirement must adapt to the reality posed by
      longer lives. The modern world is characterised by perpetual - and sometime rapid
      - change. Transformation throughout the second half of the 20th century brought
      about substantial shifts in the health and longevity of people in societies
      across the world. Since the beginning of the 21st century, the impacts of
      population ageing have gathered greater awareness in public consciousness and
      within the policy arena. Notions of old age, retirement, and later life have been
      fundamentally transformed, presenting stark challenges alongside novel
      opportunities for individuals, communities, and governments. Many of the topics
      of interest with respect to ageing populations are themselves the result of
      shifts that were unforeseen.

PMID- 24931301
TI  - Photodegradable hydrogels for capture, detection, and release of live cells.
AB  - Cells may be captured and released using a photodegradable hydrogel (photogel)
      functionalized with antibodies. Photogel substrates were used to first isolate
      human CD4 or CD8 T-cells from a heterogeneous cell suspension and then to release
      desired cells or groups of cells by UV-induced photodegradation. Flow cytometry
      analysis of the retrieved cells revealed approximately 95% purity of CD4 and CD8
      T-cells, suggesting that this substrate had excellent specificity. To demonstrate
      the possibility of sorting cells according to their function, photogel substrates
      that were functionalized with anti-CD4 and anti-TNF-alpha antibodies were
      prepared. Single cells captured and stimulated on such substrates were identified
      by the fluorescence "halo" after immunofluorescent staining and could be
      retrieved by site-specific exposure to UV light through a microscope objective.
      Overall, it was demonstrated that functional photodegradable hydrogels enable the
      capture, analysis, and sorting of live cells.

PMID- 24931303
TI  - Self-compassion weakens the association between hot flushes and night sweats and
      daily life functioning and depression.
AB  - OBJECTIVES: Some women find hot flushes and night sweats (HFNS) to interfere more
      in daily life and mood than others. Psychological resources may help to explain
      these individual differences. The aim of this study was to investigate the role
      of self-compassion, defined as healthy way of relating toward the self when
      dealing with difficult experiences, as a potential moderator of the relationship
      between HFNS and daily life activities, which in turn influences symptoms of
      depression. STUDY DESIGN: This was a cross-sectional study using questionnaire
      data from 206 women aged 40-60 who were currently experiencing hot flushes and/or
      night sweats. Path analysis was used to model relationships among menopausal
      factors (HFNS frequency and daily interference ratings), self-compassion and
      mood. MAIN OUTCOME MEASURE: Hot flush interference in daily activities and
      depressive symptoms. RESULTS: On average, women experienced 4.02 HFNS per day,
      and HFNS frequency was moderately correlated with interference ratings (r=0.38).
      In the path analytic model, self-compassion made significant direct contribution
      to hot flush interference ratings (beta=-0.37) and symptoms of depression (beta=
      0.42), and higher self-compassion was associated with lower interference and
      depressive symptoms. Self-compassion also moderated the relationship between HFNS
      frequency and hot flush interference. Higher self-compassion was associated with
      weaker effects of HFNS frequency on daily interference. CONCLUSIONS: Self
      compassion may weaken the association between HFNS and daily life functioning,
      which in turn, could lead to less HFNS-related mood problems. These findings
      imply that self-compassion may be a resilience factor to help women manage hot
      flushes and night sweats.

PMID- 24931304
TI  - Depression and dementia: cause, consequence or coincidence?
AB  - The relationship between depression and dementia is complex and still not well
      understood. A number of different views exist regarding how the two conditions
      are linked as well as the underlying neurobiological mechanisms at work. This
      narrative review examined longitudinal and cross sectional studies in the
      existing literature and determined the evidence supporting depression being a
      risk factor, a prodrome, a consequence, or an independent comorbidity in
      dementia. Overall there is convincing evidence to support both the notion that
      early life depression can act as a risk factor for later life dementia, and that
      later life depression can be seen as a prodrome to dementia. There is also
      evidence to support both conditions showing similar neurobiological changes,
      particularly white matter disease, either indicating shared risk factors or a
      shared pattern of neuronal damage. These findings highlight the need to examine
      if effective treatment of depressive episodes has any effect in reducing the
      prevalence of dementia, as well as clinicians being vigilant for late life
      depression indicating the incipient development of dementia, and therefore
      carefully following up these individuals for future cognitive impairment. 

PMID- 24931305
TI  - Comparison of three modifications of fused-silica capillaries and untreated
      capillaries for protein profiling of maize extracts by capillary electrophoresis.
AB  - In this work, capillary electrophoresis was applied to protein profiling of
      fractionated extracts of maize. A comparative study on the application of
      uncoated fused-silica capillaries and capillaries modified with
      hydroxypropylmethylcellulose, omega-iodoalkylammonium salt and a commercially
      available neutral capillary covalently coated with polyacrylamide is presented.
      The coating stability, background electrolyte composition, and separation
      efficiency were investigated. It was found that for zeins separation, the most
      stable and efficient was the capillary coated with polyacrylamide. Finally, the
      usefulness of these methods was studied for the differentiation of zein fraction
      in transgenic and nontransgenic maize. Zeins extracted from maize standards
      containing 0 and 5% m/m genetic modification were successfully separated, but
      slight differences were observed in terms of the zein content. Albumin and
      globulin fractions were analyzed with the use of unmodified fused-silica
      capillary with borate buffer pH 9 and the capillary coated with polyacrylamide
      with phosphate buffer pH 3. In the albumin fraction, additional peaks were found
      in genetically modified samples. 

PMID- 24931307
TI  - Genetic and metabolic analysis of the carbofuran catabolic pathway in
      Novosphingobium sp. KN65.2.
AB  - The widespread agricultural application of carbofuran and concomitant
      contamination of surface and ground waters has raised health concerns due to the
      reported toxic effects of this insecticide and its degradation products. Most
      bacteria that degrade carbofuran only perform partial degradation involving
      carbamate hydrolysis without breakdown of the resulting phenolic metabolite. The
      capacity to mineralize carbofuran beyond the benzofuran ring has been reported
      for some bacterial strains, especially sphingomonads, and some common
      metabolites, including carbofuran phenol, were identified. In the current study,
      the catabolism of carbofuran by Novosphingobium sp. KN65.2 (LMG 28221), a strain
      isolated from a carbofuran-exposed Vietnamese soil and utilizing the compound as
      a sole carbon and nitrogen source, was studied. Several KN65.2 plasposon mutants
      with diminished or abolished capacity to degrade and mineralize carbofuran were
      generated and characterized. Metabolic profiling of representative mutants
      revealed new metabolic intermediates, in addition to the initial hydrolysis
      product carbofuran phenol. The promiscuous carbofuran-hydrolyzing enzyme Mcd,
      which is present in several bacteria lacking carbofuran ring mineralization
      capacity, is not encoded by the Novosphingobium sp. KN65.2 genome. An alternative
      hydrolase gene required for this step was not identified, but the constitutively
      expressed genes of the unique cfd operon, including the oxygenase genes cfdC and
      cfdE, could be linked to further degradation of the phenolic metabolite. A third
      involved oxygenase gene, cfdI, and the transporter gene cftA, encoding a TonB
      dependent outer membrane receptor with potential regulatory function, are located
      outside the cfd cluster. This study has revealed the first dedicated carbofuran
      catabolic genes and provides insight in the early steps of benzofuran ring
      degradation.

PMID- 24931308
TI  - Proteomics of arsenic stress in the gram-positive organism Exiguobacterium sp. PS
      NCIM 5463.
AB  - The general responses of microorganisms to environmental onslaughts are modulated
      by altering the gene expression pattern to reduce damage in the cell and produce
      compensating stress responses. The present study attempts to unravel the response
      of the Gram-positive Exiguobacterium sp. PS NCIM 5463 in the presence of
      [As(III)] and arsenate [As(V)] using comparative proteomics via two-dimension gel
      electrophoresis (2-DE) coupled with identification of proteins using matrix
      assisted laser desorption/ionisation (MALDI-TOF/MALDI-TOF/TOF). Out of 926
      Coomassie-stained proteins, 45 were differentially expressed (p < 0.05).
      Considering the resolution and abundance level, 24 spots (peptides) were
      subjected to MALDI analysis, identified and categorised into several functional
      categories, viz., nitrogen metabolism, energy and stress regulators, carbohydrate
      metabolism, protein synthesis components and others. A functional role of each
      protein is discussed in Exiguobacterium sp. PS 5463 under arsenic stress and
      validated at their transcript level using a quantitative real-time polymerase
      chain reaction. Unlike previous reports that unravel the responses toward arsenic
      stress in Gram-negative organisms, the present study identified new proteins
      under arsenic stress in a Gram-positive organism, Exiguobacterium sp. PS NCIM
      5463, which could elucidate the physiology of organisms under arsenic stress.

PMID- 24931309
TI  - Genes commonly involved in acid tolerance are not overexpressed in the plant
      microsymbiont Mesorhizobium loti MAFF303099 upon acidic shock.
AB  - Rhizobia are legume bacterial symbionts that fix nitrogen in the root nodules of
      plants. The aim of the present study was to investigate the global
      transcriptional response of rhizobia upon an acidic shock. Changes in the
      transcriptome of cells of Mesorhizobium loti strain MAFF303099 upon an acidic
      shock at pH 3 for 30 min were analysed. From a total of 7,231 protein-coding
      genes, 433 were found to be differentially expressed upon acidic shock, of which
      322 were overexpressed. Although most of the overexpressed genes encode
      hypothetical proteins, the two most represented Cluster of Orthologous Group
      (COG) categories are 'defence mechanisms' and 'transcription'. Differentially
      expressed genes are dispersed throughout the chromosome, with the exception of
      the symbiosis island, where most genes remain unchanged. A significant number of
      transcriptional regulators and ABC transporter genes are overexpressed. No
      overexpression of genes typically associated to acid tolerance in rhizobia, such
      as act and exo genes, was detected. Overall, this study suggests a
      transcriptional response to acidic shock of M. loti distinct from other rhizobia.
      Additional studies are in course to explore the role of some of the highly
      overexpressed genes and to further elucidate the molecular bases of acid stress
      response. 

PMID- 24931310
TI  - Calcineurin modulates growth, stress tolerance, and virulence in Metarhizium
      acridum and its regulatory network.
AB  - Calcineurin is highly conserved and regulates growth, conidiation, stress
      response, and pathogenicity in fungi. However, the functions of calcineurin and
      its regulatory network in entomopathogenic fungi are not clear. In this study,
      calcineurin was functionally analyzed by deleting the catalytic subunit MaCnA
      from the entomopathogenic fungus Metarhizium acridum. The DeltaMaCnA mutant had
      aberrant, compact colonies and blunt, shortened hyphae. Conidia production was
      reduced, and phialide differentiation into conidiogenous cells was impaired in
      the DeltaMaCnA mutant. DeltaMaCnA had thinner cell walls and greatly reduced
      chitin and beta-1,3-glucan content compared to the wild type. The DeltaMaCnA
      mutant was more tolerant to cell wall-perturbing agents and elevated or decreased
      exogenous calcium but less tolerant to heat, ultraviolet irradiation, and
      caspofungin than the wild type. Bioassays showed that DeltaMaCnA had decreased
      virulence. Digital gene expression profiling revealed that genes involved in cell
      wall construction, conidiation, stress tolerance, cell cycle control, and calcium
      transport were downregulated in DeltaMaCnA. Calcineurin affected some components
      of small G proteins, mitogen-activated protein kinase, and cyclic AMP (cAMP)
      protein kinase A signaling pathways in M. acridum. In conclusion, our results
      gave a global survey of the genes downstream of calcineurin in M. acridum,
      providing molecular explanations for the changes in phenotypes observed when
      calcineurin was deleted. 

PMID- 24931311
TI  - GlnR-mediated regulation of nitrogen metabolism in the actinomycete
      Saccharopolyspora erythraea.
AB  - Nitrogen source sensing, uptake, and assimilation are central for growth and
      development of microorganisms which requires the participation of a global
      control of nitrogen metabolism-associated genes at the transcriptional level. In
      soil-dwelling antibiotic-producing actinomycetes, this role is played by GlnR, an
      OmpR family regulator. In this work, we demonstrate that SACE_7101 is the
      ortholog of actinomycetes' GlnR global regulators in the erythromycin producer
      Saccharopolyspora erythraea. Indeed, the chromosomal deletion of SACE_7101
      severely affects the viability of S. erythraea when inoculated in minimal media
      supplemented with NaNO3, NaNO2, NH4Cl, glutamine, or glutamate as sole nitrogen
      source. Combination of in silico prediction of cis-acting elements, subsequent in
      vitro (through gel shift assays) and in vivo (real-time reverse transcription
      polymerase chain reaction) validations of the predicted target genes revealed a
      very large GlnR regulon aimed at adapting the nitrogen metabolism of S.
      erythraea. Indeed, enzymes/proteins involved in (i) uptake and assimilation of
      ammonium, (ii) transport and utilization of urea, (iii) nitrite/nitrate, (iv)
      glutamate/glutamine, (v) arginine metabolism, (vi) nitric oxide biosynthesis, and
      (vii) signal transduction associated with the nitrogen source supplied have at
      least one paralog gene which expression is controlled by GlnR. Our work
      highlights a GlnR-binding site consensus sequence (t/gna/cAC-n6-GaAAc) which is
      similar although not identical to the consensus sequences proposed for other
      actinomycetes. Finally, we discuss the distinct and common features of the GlnR
      mediated transcriptional control of nitrogen metabolism between S. erythraea and
      the model organism Streptomyces coelicolor. 

PMID- 24931312
TI  - The combination of microneedles with electroporation and sonophoresis to enhance
      hydrophilic macromolecule skin penetration.
AB  - The objective of the present work was to investigate the effects of 3
      combinatorial techniques (microneedle (MN), electroporation (EP), and
      sonophoresis (SN)) on the in vitro skin permeation of the hydrophilic
      macromolecular compound fluorescein isothiocyanate-dextran (FD-4; molecular
      weight (MW) 4.4 kDa). Assessment of the in vitro skin permeation of FD-4 was
      performed in porcine skin. MN, EP, and SN were used as physical enhancement
      methods, given the potential of their various mechanisms. The total cumulative
      amount of FD-4 that permeated through treated skin using 2 or 3 combined methods,
      i.e., MN+EP, MN+SN, EP+SN, and MN+EP+SN, was investigated. Microconduits created
      by MN alone and in combination with the other techniques were observed under
      confocal laser scanning microscopy (CLSM). The histology of the treated skin was
      examined. In vitro skin permeation experiments revealed that the total cumulative
      amount of FD-4 that permeated porcine skin using 3 combined techniques (MN+EP+SN)
      was greater than the amount observed using a single method or 2 combinations
      (MN+EP, MN+SN, SN+EP). The histological images indicate no noticeable damage in
      the skin treated with all of the enhancement methods. These results suggest that
      MN+EP+SN may serve as a potentially effective combination strategy to
      transdermally deliver various hydrophilic macromolecules without causing
      structural alterations or skin damage. 

PMID- 24931313
TI  - Creation of cisplatin-adsorbing regenerative-medicine gelatin sponge and its
      Cisplatin release pattern.
AB  - The purpose of this study was to clarify the adsorption of cisplatin on
      regenerative-medicine (RM) gelatin sponge, and to verify the relationship between
      the cisplatin release pattern of cisplatin-adsorbed RM gelatin sponge and the
      dissolving time of RM gelatin sponge. We tested various RM gelatin sponges, one
      with a molecular weight of 50000 Daltons (RM-50 gelatin sponge) that is 100%
      saline soluble at 24 h, RM-50-120 (heated at 120 degrees C) that is 54.3% saline
      soluble at 24 h, and RM-50-140 (heated at 140 degrees C) that is 15.8% saline
      soluble at 24 h. We investigated the production of cisplatin-adsorbed RM gelatin
      sponge and measured free cisplatin released from cisplatin-adsorbed RM gelatin
      sponge. There was no significant difference in the weight of adsorbed cisplatin
      among the RM-50, RM-50-120, and RM-50-140. The results mean that cisplatin
      adsorbs onto RM gelatin sponge irrespective of heating temperature. The average
      adsorbed weight of cisplatin per gram of RM gelatin sponge was 29.3 mg, which was
      approximately five times more than that per g previously reported for Gelpart
      (non-soluble gelatin sponge, clinically available). Cisplatin release in the RM
      50 gelatin was the most rapid at only 1 h after incubation; it was released
      gradually and increasingly in the RM-50-120 gelatin, and released slowly in the
      RM-50-140 gelatin for 24 h incubation. Cisplatin-adsorbed RM gelatin sponge
      released cisplatin proportional to the dissolving time of RM gelatin sponge,
      indicating that the cisplatin release time can be controlled by heating for
      sterilization of RM gelatin sponge.

PMID- 24931315
TI  - Socioeconomic evaluation of well-characterized allergy to staple foods in adults.
AB  - BACKGROUND: The aim of the present study was to evaluate if total, direct,
      indirect, and intangible costs differ between a cohort of adults with well
      characterized allergy to staple foods ('cases') and controls. METHODS: Swedish
      adults with objectively diagnosed food allergy to cow's milk, hen's egg, and/or
      wheat were recruited at an outpatient allergy clinic. Controls age- and sex
      matched to cases were recruited from the same geographic area. For assessing the
      household costs of food allergy, a disease-specific socioeconomic questionnaire,
      developed within EuroPrevall, was utilized. RESULTS: Overall annual total costs
      at the household level were significantly higher among adults with food allergy
      compared with controls (the difference amounted to 8164 ?), whereas direct costs
      did not differ between cases and controls. However, household healthcare costs
      and costs for medicines were significantly higher for cases vs controls.
      Furthermore, indirect costs were significantly higher for households with food
      allergic adults vs households without food-allergic adults. Specifically, more
      time was spent on performing domestic tasks due to a family member's food-allergy
      related illness, as well as shopping and preparing food, and seeking food-allergy
      related information. Presence of food allergy also affected intangible costs.
      Adults with food allergy experienced overall lower health status compared with
      controls. CONCLUSIONS: Swedish adults with allergy to staple foods have higher
      total costs determined as direct, indirect, and intangible costs using the
      disease-specific socioeconomic questionnaire. Thus, total costs were 8164 ?
      higher per year in households with at least one adult allergic to staple foods
      compared with controls.

PMID- 24931314
TI  - Cost comparison analysis of open versus laparoscopic distal pancreatectomy.
AB  - BACKGROUND: In comparison with open distal pancreatectomy (ODP), laparoscopic
      distal pancreatectomy (LDP) is associated with fewer complications and shorter
      hospital stays, but comparative cost data for the two approaches are limited.
      METHODS: Records of all distal pancreatectomies carried out from January 2009 to
      June 2013 were reviewed and stratified according to operative complexity. Patient
      factors and outcomes were recorded. Total variable costs (TVCs) were tabulated
      for each patient, and stratified by category [e.g. 'floor', 'operating room'
      (OR), 'radiology']. Costs for index admissions and 30-day readmissions were
      compared between LDP and ODP groups. RESULTS: Of 153 procedures, 115 (70 LDP, 45
      ODP) were selected for analysis. The TVC of the index admission was US$3420 less
      per patient in the LDP group (US$10 480 versus US$13 900; P = 0.06). Although OR
      costs were significantly greater in the LDP cohort (US$5756 versus US$4900; P =
      0.02), the shorter average hospitalization in the LDP group (5.2 days versus 7.7
      days; P = 0.01) resulted in a lower overall cost. The total cost of index
      hospitalization combined with readmission was significantly lower in the LDP
      cohort (US$11 106 versus US$14 803; P = 0.05). CONCLUSIONS: In appropriately
      selected patients, LDP is more cost-effective than ODP. The increased OR cost
      associated with LDP is offset by the shorter hospitalization. These data clarify
      targets for further cost reductions.

PMID- 24931317
TI  - Missing data sensitivity analysis for recurrent event data using controlled
      imputation.
AB  - Statistical analyses of recurrent event data have typically been based on the
      missing at random assumption. One implication of this is that, if data are
      collected only when patients are on their randomized treatment, the resulting de
      jure estimator of treatment effect corresponds to the situation in which the
      patients adhere to this regime throughout the study. For confirmatory analysis of
      clinical trials, sensitivity analyses are required to investigate alternative de
      facto estimands that depart from this assumption. Recent publications have
      described the use of multiple imputation methods based on pattern mixture models
      for continuous outcomes, where imputation for the missing data for one treatment
      arm (e.g. the active arm) is based on the statistical behaviour of outcomes in
      another arm (e.g. the placebo arm). This has been referred to as controlled
      imputation or reference-based imputation. In this paper, we use the negative
      multinomial distribution to apply this approach to analyses of recurrent events
      and other similar outcomes. The methods are illustrated by a trial in severe
      asthma where the primary endpoint was rate of exacerbations and the primary
      analysis was based on the negative binomial model.

PMID- 24931316
TI  - Incremental value of three-dimensional echocardiography over the two-dimensional
      technique in the assessment of combined sinus of valsalva rupture into the right
      ventricle and adjacent perimembranous ventricular septal defect.
AB  - We describe the incremental value of live/real time three-dimensional (3D)
      echocardiography over the 2D technique in the assessment of ruptured right sinus
      of Valsalva into the right ventricle associated with an adjacent perimembranous
      ventricular septal defect in an elderly patient. 

PMID- 24931318
TI  - Beneficial cardiovascular remodeling following arterio-venous fistula ligation
      post-renal transplantation: a longitudinal magnetic resonance imaging study.
AB  - Despite improvements in survival following renal transplantation, high rates of
      cardiovascular morbidity and mortality remain. Persistence of arterio-venous
      fistulae (AVF) may contribute to maladaptive cardiovascular remodeling and poor
      health outcomes in this cohort. Utilizing recent advances in cardiovascular
      magnetic resonance imaging (CMR), we prospectively evaluated alterations in
      cardiac and vascular structure and function six months after elective ligation of
      AVF, following stable, successful renal transplantation. Eighteen subjects
      underwent CMR evaluation of cardiac structure and function, aortic distensibility
      and endothelial function prior to AVF ligation and at six months. At follow-up,
      while left ventricular ejection fraction was unchanged, mean cardiac output
      decreased by 15.6% (9.6 +/- 2.9 L/min vs. 8.1 +/- 2.3 L/min, p = 0.004) and left
      ventricular mass had regressed by 10% (166 +/- 56 g vs. 149 +/- 51 g, p =
      0.0001). Significant improvements were also noted in right ventricular and
      biatrial structure and function. Aortic distensibility was unchanged at follow
      up, but endothelial dependent vasodilatation had improved (2.5 +/- 6.5% vs. 8.0
      +/- 5.9%, p = 0.04). Elective AVF ligation following successful renal
      transplantation is associated with improvements in left ventricular mass, right
      ventricular, and biatrial structure and function. Further randomized studies are
      warranted to determine the potential clinical improvement following AVF ligation
      in this cohort.

PMID- 24931320
TI  - [Congenital Mullerian anomalies and delivery: analysis of 304 cases between 2000
      and 2010 at the University Hospital of Lille].
AB  - OBJECTIVES: This study aimed to determine the conditions and way of delivery in
      women with congenital uterine malformations. PATIENTS AND METHODS: This
      retrospective study included a cohort of patients with malformed uterus giving
      birth in Lille University Hospital between 2000 and 2010, features such as way of
      delivery, labour, foetal presentation were compared with those patients without
      uterine malformation. RESULTS: Patients with uterine anomalies had significantly
      higher rates of breech presentation (36.51% vs 4.52%; P<0.01) and cesarean
      section (55.26% vs 18.70%; P<0.01) compared to the group of women with a normal
      uterus. DISCUSSION AND CONCLUSION: Our results suggest that women with uterine
      malformation should be informed that they have an increased risk of caesarean
      section due to more frequent malpresentations.

PMID- 24931319
TI  - Demonstration of fast and accurate discrimination and quantification of
      chemically similar species utilizing a single cross-selective chemiresistor.
AB  - Performance characteristics of gas-phase microsensors will determine the ultimate
      utility of these devices for a wide range of chemical monitoring applications.
      Commonly employed chemiresistor elements are quite sensitive to selected
      analytes, and relatively new methods have increased the selectivity to specific
      compounds, even in the presence of interfering species. Here, we have focused on
      determining whether purposefully driven temperature modulation can produce faster
      sensor-response characteristics, which could enable measurements for a broader
      range of applications involving dynamic compositional analysis. We investigated
      the response speed of a single chemiresitive In2O3 microhotplate sensor to four
      analytes (methanol, ethanol, acetone, 2-butanone) by systematically varying the
      oscillating frequency (semicycle periods of 20-120 ms) of a bilevel temperature
      cycle applied to the sensing element. It was determined that the fastest response
      (~ 9 s), as indicated by a 98% signal-change metric, occurred for a period of 30
      ms and that responses under such modulation were dramatically faster than for
      isothermal operation of the same device (>300 s). Rapid modulation between 150
      and 450  degrees C exerts kinetic control over transient processes, including
      adsorption, desorption, diffusion, and reaction phenomena, which are important
      for charge transfer occurring in transduction processes and the observed response
      times. We also demonstrate that the fastest operation is accompanied by excellent
      discrimination within a challenging 16-category recognition problem (consisting
      of the four analytes at four separate concentrations). This critical finding
      demonstrates that both speed and high discriminatory capabilities can be realized
      through temperature modulation. 

PMID- 24931321
TI  - [Premature delivery: a traumatic birth? Posttraumatic stress symptoms and
      associated features].
AB  - OBJECTIVES: While researches focusing on posttraumatic stress disorder (PTSD)
      symptoms following childbirth tend to develop, few studies have been conducted on
      French samples. The aim of the current study was to explore the prevalence rate
      of women developing postpartum PTSD following preterm birth and highlighting
      associated features. PATIENTS AND METHOD: In the 4weeks following the preterm
      infant's hospital discharge, a sample of 110 French women (mean age [SD]=29.5
      [4.3]years) who delivered prematurely completed questionnaires assessing PTSD
      symptoms (Impact of Event Scale-Revised) postpartum depressive symptomatology
      (Edinburgh Postnatal Depression Scale), quality of marital relationship (Dyadic
      Adjustment Scale) and partner support (Multidimensional Scale of Perceived Social
      Support). Sociodemographic and gynecologic data were also gathered. RESULTS:
      Thirty percent of our sample reported a score on the IES-R highlighting a
      probable posttraumatic stress disorder. Increased postpartum depressive symptoms
      (beta=0.47, P<0.05), having undergone a caesarian section (beta=0.24, P<0.05),
      and prior traumatic event (beta=0.20, P<0.05), were independently associated with
      the intensity of PTSD symptoms. DISCUSSION AND CONCLUSION: Given the traumatic
      impact of preterm birth on mothers, further studies focusing on the trauma of
      premature delivery are warranted.

PMID- 24931324
TI  - Oxygen supplementation in the neonatal period: changing the paradigm.
AB  - Oxygen is one of the most widely used drugs in the neonatal period. A lack of
      knowledge of oxygen metabolism and toxicity has prompted guidelines to fluctuate
      from liberal use to treat respiratory distress to restriction to avoid
      retinopathy of prematurity. In recent years, studies performed in the immediate
      postnatal period have revealed that newly born infants achieve a stable
      saturation only several minutes after birth. Moreover, the time needed to reach a
      saturation plateau is inversely proportional to a newborn's gestational age. As a
      consequence, guidelines have changed and recommend an individualized
      supplementation in the first minutes after birth with the inspiratory fraction of
      oxygen titrated against preductal pulse oximetry. However, randomized controlled
      trials have concluded that, after postnatal stabilization, keeping preterm babies
      within a low-saturation target range (85-89%) may lead to increased mortality
      while keeping them in a higher saturation range (91-95%) increases the risk of
      retinopathy of prematurity. The present state of the art in the management of
      oxygen supplementation recommends that caregivers in the delivery room allow
      preductal oxygen saturation to spontaneously increase in the first minutes of
      life; however, if supplemented, it should be titrated according to pulse oximeter
      readings and kept within the safe margins of the nomogram. Thereafter, if oxygen
      is still needed, it should be kept within stringent security margins (90-95%) to
      avoid deleterious consequences. Importantly, in babies with chronic lung disease,
      oxygen should be supplemented to allow the patient to grow and develop.

PMID- 24931323
TI  - More about surfactant, oxygen, caffeine and chronic lung disease.

PMID- 24931325
TI  - Caffeine for apnea of prematurity: a neonatal success story.
AB  - Caffeine, a methylxanthine and nonspecific inhibitor of adenosine receptors, is
      an example of a drug that has been in use for more than 40 years. It is one of
      the most commonly prescribed drugs in neonatal medicine. However, until 2006, it
      had only a few relatively small and short-term studies supporting its use. It is
      thanks to the efforts of Barbara Schmidt and the Caffeine for Apnea of
      Prematurity (CAP) Trial Group that we now have high-quality and reliable data not
      only on short-term but also long-term outcomes of caffeine use for apnea of
      prematurity. CAP was an international, multicenter, placebo-controlled randomized
      trial designed to determine whether survival without neurodevelopmental
      disability at a corrected age of 18 months is improved if apnea of prematurity is
      managed without methylxanthines in infants at a high risk of apneic attacks. CAP
      was kept simple and pragmatic in order to allow for maximum generalizability and
      applicability. Infants with birth weights of 500-1,250 g were enrolled during the
      first 10 days of life if their clinicians considered them to be candidates for
      methylxanthine therapy. The most frequent indication for therapy reported in CAP
      was treatment of documented apnea, followed by the facilitation of the removal of
      an endotracheal tube. Only about 20% of the neonatologists in the trial started
      caffeine for the prevention of apnea and the findings of CAP cannot automatically
      be extrapolated to an exclusive prophylactic indication. However, recent data
      suggest that the administration of prophylactic methylxanthine by neonatologists
      is now common practice.

PMID- 24931322
TI  - Recombinant factor VIIa analog in the management of hemophilia with inhibitors:
      results from a multicenter, randomized, controlled trial of vatreptacog alfa.
AB  - BACKGROUND: Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with
      three amino acid substitutions and 99% identity to native FVIIa, was developed to
      improve the treatment of hemophilic patients with inhibitors. OBJECTIVES: To
      confirm the safety and assess the efficacy of vatreptacog alfa in treating
      bleeding episodes in hemophilic patients with inhibitors. PATIENTS AND METHODS:
      In this international, multicenter, randomized, double-blind, active-controlled,
      crossover, confirmatory phase III trial (adept(TM) 2) in patients with hemophilia
      A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog
      alfa (one to three doses at 80 MUg kg(-1) ) or rFVIIa (one to three doses at 90
      MUg kg(-1) ). Treatment failures after three doses of trial product (TP) were
      managed according to the local standard of care. RESULTS: In the 72 patients
      enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave
      93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa
      in secondary efficacy outcomes, including the number of doses used to treat a
      bleed and sustained bleeding control 24-48 h after the first dose. Eight patients
      (11%) developed antibodies against vatreptacog alfa, including four with cross
      reactivity against rFVIIa and one with an in vitro neutralizing effect to
      vatreptacog alfa. CONCLUSIONS: This large randomized controlled trial confirmed
      the well-established efficacy and safety profile of rFVIIa, and showed that
      vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of
      the development of anti-drug antibodies, a positive benefit-risk profile is
      unlikely to be achieved with vatreptacog alfa.

PMID- 24931328
TI  - Ethical pitfalls in neonatal comparative effectiveness trials.
AB  - Evidence-based medicine has been embraced wholeheartedly, and rightly so, as the
      best approach for reducing clinical uncertainty and ensuring that patients
      receive treatment and care that are efficacious (i.e. they work) and effective
      (i.e. they work in real life). High-quality evidence comes from high-quality
      clinical research. It would hence be reasonable to assume that these two would
      form a closely integrated partnership. Alas, this is not yet the case. So many
      uncertainties in medical care relate to treatments and practices already widely
      in use. In neonatal medicine, for example, some of us use protein-carbohydrate
      fortification of human milk and some of us do not, some of us stop enteral feeds
      during blood transfusions whereas some of us do not, some of us reach for
      dopamine when blood pressure falls while some of us use dobutamine. For our
      patients, these uncertainties represent a lottery, the throw of the dice that
      determines whether they receive the treatment advocated by Dr. A or Dr. B. They
      deserve better than this. Randomization is considered the gold standard approach
      to eliminating the clinician bias that very often dominates the choice of
      treatments. Randomization reduces the influence on outcomes of confounding by
      unknown factors, and ensures that every patient has a fair and equal chance of
      receiving the best possible treatment when this is, in fact, not known. In an
      ideal world, every medical uncertainty would be addressed in this way. The
      evaluation of treatments that are in accepted use has been termed 'comparative
      effectiveness research', i.e. the comparison of existing healthcare interventions
      to determine which works best, for whom and under which circumstances. Recently a
      long-standing uncertainty, the optimum saturation target for preterm babies
      receiving oxygen was put to the test of randomization. The accepted standard-of
      care saturation range of 85-95% has been used for a considerable time and its use
      is intended to avoid both levels of oxygen that are too low or too high.
      Investigators in the UK, Australia, New Zealand and the USA designed randomized
      controlled trials to provide more precise guidance, by determining whether
      targeting the lower end of the accepted range (85-89%) resulted in reduced
      retinopathy of prematurity when compared with the upper end of the accepted range
      (91-95%). Between 2004 and 2009, the US SUPPORT trial (Surfactant, Positive
      Pressure and Oxygenation Randomized Trial) recruited approximately 1,300 infants
      and showed that babies at the higher end of the recommended oxygen saturation
      range had a greater incidence of retinopathy of prematurity, but that,
      unexpectedly, babies at the lower end had a higher risk of death [1]. The data
      monitoring committees of the BOOST II (Oxygen Saturation and Outcomes in Preterm
      Infants) trials in the UK, Australia and New Zealand reviewed their interim data,
      confirmed the higher risk of death in babies randomized to the lower saturation
      range, and halted further recruitment [2]. Without the trials, the lower
      saturation target would have continued to be applied to many babies, and many
      would have died as a result. Though many uncertainties remain, the trials
      facilitated advances in care. However, in March 2013, the lead investigators for
      the SUPPORT trial were informed by the US 'Office for Human Research Protections'
      that they were 'in violation of the regulatory requirements for informed consent,
      stemming from the failure to describe the reasonably foreseeable risks of
      blindness, neurological damage and death' [3]. This extraordinary conclusion
      indicates that the US regulators considered the researchers to be at fault for
      failing to foresee an unexpected trial result, and for randomizing babies to
      receive oxygen within the accepted standard-of-care limits. The ruling further
      implies that the regulators consider that clinicians are acting ethically when
      they deliver an accepted but non-evidence-based treatment based upon their
      personal bias, but are acting unethically when they make the selection by
      randomization. Clearly, there is a gulf between the view of the medical
      profession and that of the regulators regarding the ethical and scientific
      validity of randomization as a means to select treatments in comparative
      effectiveness research aimed at reducing uncertainties in care. What are the ways
      forward? I suggest that, in order for medicine to advance, a paradigm shift is
      necessary, involving a deeper public (and regulator) understanding of
      randomization as the fairest approach to allocating treatments that are in wide
      and accepted use, but where the evidence base is actually uncertain, so that the
      chance of receiving the as yet unknown best treatment is unaffected by clinician
      bias, and where care is delivered along a clearly designed, closely monitored
      pathway. In practice, peer review, regulatory approval, patient involvement and
      the delivery of explanation and information would be the same as for research
      involving experimental treatments. The key difference would be that randomization
      would be the recommended default and patients would be offered the opportunity to
      opt out, rather than be invited to opt in. For neonatal medicine, this would
      reduce the risk of 'injurious misconception', where trial entry is
      inappropriately rejected by parents because of an exaggerated and
      disproportionate perception of risk [4] that is brought on or magnified by the
      burden of making decisions at this difficult and stressful time. Randomization to
      treatments that fall within accepted practice and are considered standard-of-care
      involves no research-related risks to participants, and as trial data can
      increasingly be extracted from electronic clinical records [5], the costs and
      burden of data collection placed upon clinical teams will be minimized and,
      ultimately, the resolution of uncertainties about treatment can be hastened. It
      should also be noted that this approach fulfils the four cardinal principles of
      research ethics, namely: autonomy, justice, beneficence and nonmaleficence as
      well as upholding the responsibility of all doctors to strive to reduce
      uncertainty in the care they provide to their patients [6].

PMID- 24931326
TI  - The molecular era of surfactant biology.
AB  - Advances in the physiology, biochemistry, molecular and cell biology of the
      pulmonary surfactant system transformed the clinical care and outcome of preterm
      infants with respiratory distress syndrome. The molecular era of surfactant
      biology provided genetic insights into the pathogenesis of pulmonary disorders,
      previously termed 'idiopathic', that affect newborn infants, children and adults.
      Knowledge related to the structure and function of the surfactant proteins and
      their roles in alveolar homeostasis has provided new diagnostic, prognostic and
      therapeutic tools to advance our understanding of the causes and treatments of
      acute and chronic lung diseases. Severe lung disease in newborn infants and older
      patients is caused by mutations in genes regulating alveolar epithelial cells and
      surfactant homeostasis. Mutations in genes encoding the surfactant proteins,
      transcription factors critical for alveolar morphogenesis and surfactant
      clearance, are now known to play important roles in the pathogenesis of chronic
      lung diseases. Identification of the genes underlying the diseases of alveolar
      homeostasis is useful for the diagnosis of lung disease before and after birth.

PMID- 24931327
TI  - Clinical pharmacology in neonates: small size, huge variability.
AB  - Drug therapy is a powerful tool for improving neonatal outcome. Despite this,
      neonatologists still routinely prescribe off-label compounds developed for adults
      and extrapolate doses from those used for children or adults. Knowledge
      integration through pharmacokinetic modeling is a method that could improve the
      current situation. Such predictive models may convert neonatal pharmacotherapy
      from explorative to confirmatory. This can be illustrated by research projects
      related to the prediction of neonatal renal clearance and neonatal
      glucuronidation. This type of model will also improve the current knowledge of
      neonatal (patho)physiology. In the meanwhile, the fields of clinical pharmacology
      (e.g. pharmacokinetic/pharmacodynamic modeling and pharmacogenetics) and
      neonatology (e.g. whole-body cooling and the lower limit of viability) have both
      matured, resulting in new research topics. However, in order for the modeling and
      the newly emerging topics to become effective tools, they need to be tailored to
      the specific characteristics of neonates. Consequently, the field of neonatal
      pharmacotherapy needs dedicated neonatologists who continue to raise the
      awareness that off-label practices, eminence-based dosing regimens and the
      absence of neonatal drug formulations all reflect suboptimal care.

PMID- 24931330
TI  - Abstracts of the 29th. International Workshop on Surfactant Replacement, May 30
      31, 2014, Valencia, Spain.

PMID- 24931329
TI  - Chronic lung disease of prematurity: long-term respiratory outcome.
AB  - Chronic respiratory morbidity is a common adverse outcome of preterm birth,
      especially in infants who develop bronchopulmonary dysplasia (BPD), which is
      still a major cause of long-term lung dysfunction with a heavy burden on health
      care services and medical resources throughout childhood. The most severely
      affected patients remain symptomatic even in adulthood, and this may be
      influenced also by environmental variables (e.g. smoking), which can contribute
      to persistent obstruction of airflow. Of all obstructive lung diseases in humans,
      BPD has the earliest onset and probably lasts the longest. Since the prevention
      of BPD is an elusive goal, minimizing neonatal lung injury and closely monitoring
      survivors remain the best courses of action. This review describes the clinical
      and functional changes characteristic of the long-term pulmonary sequelae of
      preterm birth, focusing particularly on BPD.

PMID- 24931331
TI  - Pregnancy-associated plasma protein A regulates mitosis and is epigenetically
      silenced in breast cancer.
AB  - Aberrant mitosis is a common feature of cancer, yet little is known about the
      altered genes causing mitotic defects. We screened human tumours for cells with
      morphological signatures of highly specific mitotic defects previously assigned
      to candidate genes in a genome-wide RNA interference screen carried out in HeLa
      cells (www.mitocheck.org). We discovered a striking enrichment of early mitotic
      configurations indicative of prophase/prometaphase delay in breast cancer.
      Promoter methylation analysis of MitoCheck candidate genes assigned to the
      corresponding 'mitotic delay' class linked this defect to epigenetic silencing of
      the gene encoding pregnancy-associated plasma protein-A (PAPPA), a secreted
      protease. PAPPA silencing was highly prevalent in precursor lesions and invasive
      breast cancer. Experimental manipulation of PAPPA protein levels in human mammary
      epithelial cells and in breast cancer cell lines demonstrates that progression
      through early mitosis is dependent on PAPPA function, and that breast cancer
      cells become more invasive after down-regulation of this protease. PAPPA
      regulates mitotic progression through modulating the IGF-1 signalling pathway
      resulting in activation of the forkhead transcription factor FoxM1, which drives
      a transcriptional cluster of essential mitotic genes. Our results show that PAPPA
      has a critical function in normal cell division and is targeted early in breast
      cancer development.

PMID- 24931332
TI  - Antiobesity medication use across the veterans health administration: patient
      level predictors of receipt.
AB  - OBJECTIVE: Pharmacotherapy is an effective adjunct to behavioral interventions to
      treat obesity; although it is unclear how often medications are integrated into
      obesity treatment plans and for which patients in the Veterans Health
      Administration (VHA). METHODS: A retrospective cohort study was conducted that
      examined variation in and predictors of antiobesity medication receipt (orlistat)
      among > 2 million obese Veterans within 140 facilities nationwide. RESULTS: One
      percent of all obese patients using VHA services filled a prescription for
      orlistat. Veterans were more likely to be treated with orlistat if they had a
      higher BMI, were female, unmarried, younger, a minority, had home instability,
      prescribed obesogenic psychiatric medications, had a psychiatric or obesity
      related comorbidity, and used MOVE! weight management services. Among those who
      likely met the criteria for use, 2.5% had at least one orlistat prescription.
      Facility-level prescription rates varied from 0 to 1% of all obese patients in a
      VA facility receiving a prescription and 0 to 21% among those who met the
      criteria for use. CONCLUSIONS: Consistent with guidelines recommending that
      obesity pharmacotherapy be prescribed in conjunction with behavioral therapy, the
      strongest predictor of receiving orlistat was being enrolled in the MOVE! weight
      loss management program.

PMID- 24931333
TI  - Treatment with human insulin does not increase thyroid cancer risk in patients
      with type 2 diabetes.
AB  - BACKGROUND: Whether human insulin therapy may increase thyroid cancer risk in
      patients with type 2 diabetes mellitus (T2DM) has not been investigated.
      MATERIALS AND METHODS: The reimbursement databases of all Taiwanese diabetic
      patients from 1996 to 2009 were retrieved from the Bureau of National Health
      Insurance. The entry date was set at 1 January 2004, and 968,384 patients with
      T2DM were followed up for thyroid cancer incidence until the end of 2009. Ever
      users, never-users and subgroups of human insulin exposure (using tertile cut
      offs of time since starting insulin, duration of therapy and cumulative dose) at
      entry date were calculated for thyroid cancer incidence. Insulin glargine was not
      marketed until after the entry date. Therefore, to exclude the potential
      contamination of insulin glargine, patients who happened to use insulin glargine
      were censored at the time of its initiation when calculating the period of follow
      up. Hazard ratios were estimated by Cox regression. RESULTS: There were 111,121
      ever-users and 857,263 never-users of human insulin, with respective numbers of
      incident thyroid cancer of 118 (0.11%) and 1047 (0.12%), and respective
      incidences of 23.9 and 23.8 per 100,000 person-years. The overall hazard ratios
      (95% confidence intervals) did not show a significant association with human
      insulin in either the age-sex-adjusted or the fully adjusted model: 0.942 (0.778
      1.141) and 1.096 (0.888-1.353), respectively. When categorized into tertiles of
      the dose-response parameters, none of the hazard ratios was significant.
      CONCLUSIONS: This study does not support the role of human insulin therapy in
      increasing the risk of thyroid cancer in patients with T2DM.

PMID- 24931335
TI  - Helichrysum arenarium subsp. arenarium: phenolic composition and antibacterial
      activity against lower respiratory tract pathogens.
AB  - The aim of this study was to investigate the phenolic content and antibacterial
      activity of the methanol extract from Helichrysum arenarium (L.) Moench subsp.
      arenarium inflorescences against lower respiratory tract pathogens (standard
      strains and clinical isolates). The extract was characterised by a total phenolic
      content of 160.17 mg/g. Several caffeic acid conjugates (chlorogenic acid and
      dicaffeoylquinic acids) and flavonoids (apigenin, naringenin, apigenin-7-O
      glucoside and naringenin-O-hexosides) were identified as major constituents by
      HPLC-DAD-ESI-MS. Staphylococcus aureus ATCC 25923 was more susceptible to
      Helichrysum extract than Streptococcus pneumoniae ATCC 49619 (minimum inhibitory
      concentration [MIC] = 0.62  and 1.25 mg/mL, respectively). The extract exhibited
      similar antibacterial effects against methicillin-resistant S. aureus and
      penicillin-resistant S. pneumoniae clinical isolates (MIC = 2.5 mg/mL) displaying
      a higher activity against ampicillin-resistant Moraxella catarrhalis isolate (MIC
      = 0.15 mg/mL). The combination with ciprofloxacin exhibited additivity against
      both standard strains (fractional inhibitory concentration [FIC] index = 0.75 and
      0.73) and S. aureus isolates (FIC index = 0.62) and synergy against S. pneumoniae
      isolates (FIC index = 0.5). 

PMID- 24931334
TI  - Effectiveness and limitations of local structural entropy optimization in the
      thermal stabilization of mesophilic and thermophilic adenylate kinases.
AB  - Local structural entropy (LSE) is a descriptor for the extent of conformational
      heterogeneity in short protein sequences that is computed from structural
      information derived from the Protein Data Bank. Reducing the LSE of a protein
      sequence by introducing amino acid mutations can result in fewer conformational
      states and thus a more stable structure, indicating that LSE optimization can be
      used as a protein stabilization method. Here, we describe a series of LSE
      optimization experiments designed to stabilize mesophilic and thermophilic
      adenylate kinases (AKs) and report crystal structures of LSE-optimized AK
      variants. In the mesophilic AK, thermal stabilization by LSE reduction was
      effective but limited. Structural analyses of the LSE-optimized mesophilic AK
      variants revealed a strong correlation between LSE and the apolar buried surface
      area. Additional mutations designed to introduce noncovalent interactions between
      distant regions of the polypeptide resulted in further stabilization.
      Unexpectedly, optimizing the LSE of the thermophilic AK resulted in a decrease in
      thermal stability. This destabilization was reduced when charged residues were
      excluded from the possible substitutions during LSE optimization. These
      observations suggest that stabilization by LSE reduction may result from the
      optimization of local hydrophobic contacts. The limitations of this process are
      likely due to ignorance of other interactions that bridge distant regions in a
      given amino acid sequence. Our results illustrate the effectiveness and
      limitations of LSE optimization as a protein stabilization strategy and highlight
      the importance and complementarity of local conformational stability and global
      interactions in protein thermal stability.

PMID- 24931336
TI  - Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon
      nanoconstructs for MR imaging of cancer.
AB  - Porous silicon has been used for the delivery of therapeutic and imaging agents
      in several biomedical applications. Here, mesoporous silicon nanoconstructs
      (SiMPs) with a discoidal shape and a sub-micrometer size (1000*400nm) have been
      conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA)
      molecules and proposed as contrast agents for Magnetic Resonance Imaging. The
      surface of the SiMPs with different porosities - small pore (SP: ~5nm) and huge
      pore (HP: ~40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have
      been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES)
      groups, conjugated with DOTA molecules, and reacted with an aqueous solution of
      GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd
      SiMPs achieve longitudinal relaxivities r1 of ~17 (mMs)(-)(1), which is 4 times
      greater than for free Gd(DOTA). This enhancement is ascribed to the confinement
      and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The
      resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors
      up to 2% of the injected dose per gram tissue, upon tail vein injection. All
      together this data suggests that Gd-SiMPs could be efficiently used for MR
      vascular imaging in cancer and other diseases. 

PMID- 24931337
TI  - Titanium-bone-anchored penile epithesis: preoperative planning and immediate
      postoperative results.
AB  - The principle of osseointegration is accepted and used in reconstructive surgery.
      This study presents the first series of five patients where titanium implants
      have been implanted into the pubic bones of female-to-male (FTM) transsexual
      patients, in order to attach a "bone-anchored" penile epithesis. Following
      patient selection based on patients' wishes, pubic bones of 10 FTM transsexuals
      were analysed by CT-scan and a virtual planning was made. A surgical plan was
      also developed. To date, five FTM transsexuals have undergone the two-stage
      surgery. During stage-1, two titanium implants ("fixtures") are implanted onto
      the pubic bone. Four weeks postop, a new CT scan is performed to analyze
      osseointegration and the final implant position. During stage-2, the soft tissue
      of the pubic area is reduced; abutments are inserted and passed through the skin.
      A few weeks after stage 2 surgery, a penile epithesis is connected to the skin
      penetrating titanium implants. Two out of 10 patients who received preoperative
      CT scan presented with smaller pubic bones, not able to accommodate the fixtures
      as chosen originally. Preoperative virtual planning is crucial for the selection
      of the appropriate implants size. The stage-1 and stage-2 surgery occurred
      uneventfully in all five patients. One patient presented with a wound infection 1
      week after stage-2 surgery. Postoperative CT scan demonstrates implant
      osseointegration in all cases. This experimental clinical study demonstrates that
      titanium osseointegration is feasible onto the pubic bone. This new approach for
      penile reconstruction constitutes another alternative for both transsexual
      patients and cases following genital development disorders, post-trauma and
      surgery.

PMID- 24931338
TI  - Simvastatin treatment exerts antidepressant-like effect in rats exposed to
      chronic mild stress.
AB  - Hyperlipidemia is associated with increased risk of coronary artery disease and
      stroke, both of which, in turn, are risk factors of old-age depression. Statins
      are extensively used for decreasing cholesterol levels. Clinical investigations
      revealed that long-term use of statins appeared to be associated with a lower
      risk of anxiety and depression. However, the antidepressant property of statins
      has not been well examined. This study aimed at examining the antidepressant-like
      effects of statins in rats exposed to chronic mild stress (CMS). We found that
      animals exposed to CMS for 4 weeks developed depressive-like state, shown by
      forced swim test and sucrose preference test. However, these CMS-induced
      behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days,
      comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety
      like behaviors were not altered by CMS or these treatments. These results
      demonstrated antidepressant-like effects of statin in CMS model of rats and
      suggested the potential that statins could be used to facilitate antidepressant
      treatment in clinical setting.

PMID- 24931339
TI  - Editorial comment from Dr Simonato and Dr Romagnoli to impact of obesity on the
      predictive accuracy of prostate-specific antigen density and prostate-specific
      antigen in native Korean men undergoing prostate biopsy.

PMID- 24931340
TI  - In situ gelling polyvalerolactone-based thermosensitive hydrogel for sustained
      drug delivery.
AB  - Biodegradable poly(ethyleneglycol)-poly(valerolactone)-poly(ethyleneglycol) [PEG
      PVL-PEG] copolymers were synthesized through ring opening polymerization of delta
      valerolactone (VL) followed by the coupling of monomethoxy poly(ethyleneglycol
      poly(valerolactone) (mPEG-PVL) with hexamethylene diisocyanate (HDI). The
      copolymers were characterized by (1)H NMR, FT-IR, and GPC. Block copolymers of
      PEG and PVL with different VL/PEG molar ratios were successfully synthesized. One
      of the copolymers (Copolymer 2, PEG550-PVL6768-PEG550) displayed a sol-gel
      transition at a physiological temperature based on the test tube inverting method
      and rheological studies. The thermogelling copolymer demonstrated a
      characteristic crystalline peak for PVL block as determined by DSC and XRD
      analysis. In vitro release from the copolymer hydrogel matrix indicated that
      dexamethasone (DEX), a hydrophobic model drug, released comparatively slower than
      5-fluoruracil (5-FU), a hydrophilic model drug, due to the potential partitioning
      of DEX into the PVL core. 5-FU in vitro release from copolymer 2 was 86% in 22 h,
      whereas only 14% of DEX was released in 24h. Cell viability studies confirmed
      that hydrogels composed of block copolymers are biocompatible. Copolymer 2 showed
      more than 80% relative cell viability at all concentrations, including
      concentrations greater than 200 fold CMC. In vivo gel formation studies indicate
      that gel integrity was maintained for 7 days upon subcutaneous injection into
      mice. These results indicate that PEG-PVL-PEG copolymers are suitable for drug
      delivery applications.

PMID- 24931341
TI  - Development and bioevaluation of nanofibers with blood-derived growth factors for
      dermal wound healing.
AB  - The aim of our work was to produce a modern nanomaterial with incorporated blood
      derived growth factors, produced by electrospinning, applicable in treatment of
      chronic wounds. Platelet-rich plasma was chosen as a natural source of growth
      factors. Results showed that platelet-rich plasma stimulates keratinocyte and
      fibroblast cell growth in vitro. Its optimal concentration in growth medium was
      2% (v/v) for both types of skin cells, while higher concentrations caused
      alterations in cell morphology, with reduced cell mobility and proliferation. In
      the next step hydrophilic nanofibers loaded with platelet-rich plasma were
      produced from chitosan and poly(ethylene oxide), using electrospinning. The
      morphology of nanofibers was stable in aqueous conditions for 72 h. It was shown
      that electrospinning does not adversely affect the biological activity of
      platelet-rich plasma. The effects of nanofibers with incorporated platelet-rich
      plasma on cell proliferation, survival, morphology and mobility were examined.
      Nanofibers limited cell mobility, changed morphology and stimulated cell
      proliferation. Despite of the small amount of blood-derived growth factors
      introduced in cell culture via platelet-rich plasma-loaded nanofibers, such
      nanofibrillar support significantly induced cell proliferation, indicating
      synergistic effect of nanotopography and incorporated growth factors. The overall
      results confirm favorable in vitro properties of produced nanofibers, indicating
      their high potential as a nanomaterial suitable for delivery of platelet-rich
      plasma in wound healing applications.

PMID- 24931342
TI  - Long-term doxorubicin release from multiple stimuli-responsive hydrogels based on
      alpha-amino-acid residues.
AB  - We have developed a series of pH- and temperature-stimuli-sensitive vinyl
      hydrogels, bearing alpha-amino acid residues (L-phenylalanine, L-valine) and
      incorporating magnetic nanoparticles of different chemical compositions (CoFe2O4
      and Fe3O4). The goal was to study the potential applications of these
      nanocomposites in the controlled release of doxorubicin (DOXO), a potent
      anticancer drug. The strength of the electrostatic interaction between the
      protonated nitrogen of the DOXO molecule and the ionized carboxylic groups of the
      hydrogel allowed effective control of the drug release rate in saline solutions.
      The embedded magnetic nanoparticles were an additional remote control of the drug
      release under the stimulus of an appropriate external alternating magnetic field
      (AMF). Data showed that the controlled release of DOXO proceeded for months and
      followed a diffusion-controlled release mechanism, while maintaining the amount
      of released drug within acceptable therapeutic windows. The amount of the
      released DOXO was found in all cases substantially higher than the "control"
      because the application of the AMF augments in stimulating the nanoparticles
      within the DOXO-loaded hydrogel. In vitro experiments have shown that the
      released DOXO is able to induce cell death to cervix adenocarcinoma cells (HeLa
      cells).

PMID- 24931343
TI  - Pancreatic intraepithelial neoplasia in the background of invasive ductal
      carcinoma of the pancreas as a prognostic factor.
AB  - AIMS: Of the recognized precursor lesions of pancreatic adenocarcinoma,
      pancreatic intraepithelial neoplasia (PanIN) is the most common form. However,
      little is known about the relationship between the grade of PanIN and prognosis
      for patients with invasive ductal carcinoma. METHODS AND RESULTS: In 124 patients
      with invasive ductal carcinoma, we examined the grade and number of PanIN lesions
      in all slides of resected pancreas. The prevalence rates of PanIN-1A, PanIN-1B,
      PanIN-2 and PanIN-3 were 86%, 84%, 57% and 30%, respectively. We allocated PanIN
      2 and PanIN-3 cases into a PanIN-high group, and cases showing PanIN-1A, PanIN-1B
      or absence of PanIN into a PanIN-low group. In clinicopathological analysis,
      PanIN-high status was significantly correlated with the number of PanIN lesions
      (P < 0.0001). Disease-free and overall survival were statistically better in the
      PanIN-high group than in the PanIN-low group (P = 0.0005 and P = 0.0003).
      Univariate and multivariate analyses revealed that tumour size and PanIN-low
      status were statistically significant factors for a poorer prognosis (P = 0.042
      and P = 0.007). CONCLUSIONS: In a pathological examination, it is important to
      evaluate the grade and number of PanINs in assessing the prognosis of pancreatic
      cancer.

PMID- 24931345
TI  - What is the clinical significance of isolated subsegmental pulmonary embolism?

PMID- 24931344
TI  - A computational model unifies apparently contradictory findings concerning
      phantom pain.
AB  - Amputation often leads to painful phantom sensations, whose pathogenesis is still
      unclear. Supported by experimental findings, an explanatory model has been
      proposed that identifies maladaptive reorganization of the primary somatosensory
      cortex (S1) as a cause of phantom pain. However, it was recently found that BOLD
      activity during voluntary movements of the phantom positively correlates with
      phantom pain rating, giving rise to a model of persistent representation. In the
      present study, we develop a physiologically realistic, computational model to
      resolve the conflicting findings. Simulations yielded that both the amount of
      reorganization and the level of cortical activity during phantom movements were
      enhanced in a scenario with strong phantom pain as compared to a scenario with
      weak phantom pain. These results suggest that phantom pain, maladaptive
      reorganization, and persistent representation may all be caused by the same
      underlying mechanism, which is driven by an abnormally enhanced spontaneous
      activity of deafferented nociceptive channels. 

PMID- 24931348
TI  - Endocrine surgical conditions of childhood. Preface.

PMID- 24931347
TI  - Inhibition of budding/release of porcine endogenous retrovirus.
AB  - PERV is integrated into the genome of all pigs. PERV-A and PERV-B are polytropic
      and can productively infect human cell lines, whereas PERV-C is ecotropic.
      Recombinant PERV-A/C can infect human cells and exhibits high titer replication.
      Therefore, use of pigs for human xenotransplantation raises concerns about the
      risks of transfer of this infectious agent from donors to xenotransplantation
      recipients. To establish strategies to inhibit PERV production from cells, in the
      present study, we investigated the mechanism of PERV budding and anti-PERV
      activity of Tetherin/BST-2. The results showed that DN mutants of WWP-2, Tsg101,
      and Vps4A/B markedly reduced PERV production in human and porcine cell lines,
      suggesting that PERV budding uses these cellular factors and the cellular MVB
      sorting pathway as well as many other retroviruses. Moreover, PERV production was
      also reduced by human and porcine Tetherin/BST-2. These data are useful for
      developing strategies to inhibit PERV production and may reduce the risk of PERV
      infection in xenotransplantation. 

PMID- 24931346
TI  - MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding
      factor 1 (Srebf1) exhibit reduced HDL-C in vivo.
AB  - MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs
      and inhibit translation or promote mRNA degradation. Recent reports, including
      ours, indicated that miR-33a located within the intron of sterol regulatory
      element-binding protein (SREBP) 2 controls cholesterol homeostasis and can be a
      possible therapeutic target for treating atherosclerosis. Primates, but not
      rodents, express miR-33b from an intron of SREBF1. Therefore, humanized mice, in
      which a miR-33b transgene is inserted within a Srebf1 intron, are required to
      address its function in vivo. We successfully established miR-33b knock-in (KI)
      mice and found that protein levels of known miR-33a target genes, such as ABCA1,
      ABCG1, and SREBP-1, were reduced compared with those in wild-type mice. As a
      consequence, macrophages from the miR-33b KI mice had a reduced cholesterol
      efflux capacity via apoA-I and HDL-C. Moreover, HDL-C levels were reduced by
      almost 35% even in miR-33b KI hetero mice compared with the control mice. These
      results indicate that miR-33b may account for lower HDL-C levels in humans than
      those in mice and that miR-33b is possibly utilized for a feedback mechanism to
      regulate its host gene SREBF1. Our mice will also aid in elucidating the roles of
      miR-33a/b in different genetic disease models. 

PMID- 24931349
TI  - Thyroid surgery in children.
AB  - Although surgical conditions of the thyroid gland are uncommon in children, the
      increased incidence of thyroid cancer, combined with the fact that children's
      hospitals are increasingly treating older adolescents, means that it is important
      that all pediatric surgeons have a knowledge of these conditions. Abnormalities
      of the thyroid can be associated with abnormalities of thyroid function
      (hyperthyroidism or hypothyroidism) and/or can be associated with symmetrical or
      asymmetrical enlargement of the gland.

PMID- 24931350
TI  - Parathyroid conditions in childhood.
AB  - This review of parathyroid surgery in children will briefly discuss parathyroid
      gland embryology and anatomy before focusing on the pathophysiology, clinical
      presentation, and treatment of hyperparathyroidism in children.
      Hyperparathyroidism (HPT) is the overproduction of PTH and it is rare in
      children, with an incidence of 2-5 per 100,000. This rarity means that the
      principles of caring for children with parathyroid disease are largely
      extrapolated from the richer adult experience; however, the unique pediatric
      aspects of parathyroid problems and their surgical treatment, including
      presentation, imaging, operative approach, and complications, will be considered.

PMID- 24931351
TI  - Rare adrenal tumors in children.
AB  - Apart from neuroblastomas, adrenal tumors are exceedingly rare in children and
      young adults. In this age group, the vast majority of patients present with
      clinical signs associated with excess hormone production. The most common tumor
      to arise from the adrenal cortex is an adrenocortical carcinoma (ACC). Similar to
      the situation in adults, this tumor is frequently diagnosed at a late stage and
      carries a very poor prognosis. ACCs require extensive/aggressive local resection
      followed by mitotane chemotherapy. A multidisciplinary approach is essential, and
      these children should be referred to units that have previous experience in
      managing ACCs. International registries are an invaluable source for evidence
      based care, and such collaborations should be further developed in the future.
      Pheochromocytomas are derived from the adrenal medulla and present with symptoms
      caused by high secretion of catecholamines. At least one-third of these children
      will be found to carry genetic mutations, most commonly the RET gene (MEN2
      syndrome) or the VHL gene. Open radical adrenalectomy should be offered to
      children with adrenocortical cancers. For all other cases, laparoscopic
      adrenalectomy is the treatment of choice. It is possible that the
      retroperitoneoscopic approach will gain increasing favor. The role of robotic
      adrenalectomy remains controversial.

PMID- 24931352
TI  - Persistent hyperinsulinaemic hypoglycaemia in infancy.
AB  - Persistent hyperinsulinaemic hypoglycaemia in infancy (PHHI) is a heterogeneous
      condition characterised by unregulated insulin secretion in response to a low
      blood glucose level. It is the most common cause of severe and persistent
      hypoglycaemia in neonates. It is extremely important to recognise this condition
      early and institute appropriate management to prevent significant brain injury
      leading to complications like epilepsy, cerebral palsy and neurological
      impairment. Histologically, PHHI is divided mainly into three types-diffuse,
      focal and atypical disease. Fluorine-18-l-3,4-dihydroxyphenylalanine positron
      emission tomography (18F-DOPA-PET/CT) scan allows differentiation between diffuse
      and focal diseases. The diffuse form is inherited in an autosomal recessive (or
      dominant) manner whereas the focal form is sporadic in inheritance and is
      localised to a small region of the pancreas. The molecular basis of PHHI involves
      defects in key genes (ABCC8, KCNJ11, GCK, SLC16A1, HADH, UCP2, HNF4A and GLUD1)
      that regulate insulin secretion. Focal lesions are cured by lesionectomy whereas
      diffuse disease (unresponsive to medical therapy) will require a near-total
      pancreatectomy with a risk of developing diabetes mellitus and pancreatic
      exocrine insufficiency. Open surgery is the traditional approach to pancreatic
      resection. However, recent advances in laparoscopic surgery have led to
      laparoscopic near-total pancreatectomy for diffuse lesions and laparoscopic
      distal pancreatectomy for focal lesions distal to the head of the pancreas.

PMID- 24931353
TI  - Islet cell transplantation.
AB  - Islet transplantation has become a promising treatment for selected patients with
      type 1 diabetes. Here we provide an overview of the procedure including its
      history, the process of donor selection, and the techniques and procedures
      involved in a successful transplant. A brief overview of the current
      immunosuppressive regimens, the long-term follow-up and the reported outcomes
      will also be discussed. While islet transplantation is currently generally
      reserved for adults with type 1 diabetes with severe hypoglycemia or glycemic
      lability, we herein consider the possibility of its application to the pediatric
      population.

PMID- 24931354
TI  - Gastroenteropancreatic neuroendocrine (carcinoid) tumors in children.
AB  - Neuroendocrine tumors (NETs) (previously termed carcinoids) are slow-growing
      tumors of the neuroendocrine system. They can occur anywhere within the body but
      are most commonly found in the midgut. This review is therefore confined to a
      discussion of gastroenteropancreatic NETS (GEP-NETS). GEP-NETS may be
      asymptomatic and are found incidentally (eg, during appendicectomy) or can
      present with symptoms attributable to either the site of the primary tumor or the
      secretion of serotonin and other substances from metastatic carcinoid disease
      (carcinoid syndrome). Symptoms of carcinoid syndrome include facial flushing,
      diarrhea, wheezing, colicky abdominal pain, and edema. Surgical resection offers
      the only curative treatment for neuroendocrine tumors, although peptide hormone
      analogues can be used to control carcinoid symptoms. Guidelines exist to
      determine when further surgical resection is required when NETs (carcinoids) are
      found incidentally during appendicectomy. A multi-disciplinary approach is
      essential for the management of all children with these rare and challenging
      tumors.

PMID- 24931355
TI  - Multiple endocrine neoplasia (MEN) syndromes.
AB  - Multiple endocrine neoplasia (MEN) syndromes are characterised by the combined
      occurrence of two or more endocrine tumours in a patient. These autosomal
      dominant conditions occur in four types: MEN1 due to inactivating MEN1 mutations;
      MEN2A and MEN2B (MEN3) due to activating mutations of RET and MEN4 due to
      inactivating cyclin-dependent kinase inhibitor 1B (CDKN1B) mutations. Each MEN
      syndrome exhibits different combinations of pancreatic islet, anterior pituitary,
      parathyroid, medullary thyroid and adrenal tumours. This article provides an
      overview of the clinical features, treatments and molecular genetics of each
      endocrine tumour syndrome.

PMID- 24931356
TI  - Do statins reduce the cardiovascular risk in patients with rheumatoid arthritis?
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) are at significantly higher
      risk of cardiovascular (CV) morbidity and mortality compared with the general
      population. Traditional CV risk factors cannot explain the total excess of CV
      morbidity and mortality in RA patients. At present, it is not clear whether
      treatment with statins might be of benefit in RA patients. The aim of the present
      systematic literature review is to summarize the published evidence concerning
      treatment with statins and its impact on CV events in RA patients. METHODS: A
      systematic literature review of studies on RA and statins was carried out in the
      database PubMed. Search terms were 'simvastatin OR atorvastatin OR fluvastatin OR
      lovastatin OR pravastatin OR rosuvastatin OR statin AND arthritis'. Papers were
      included in this review when the reported outcome was on CV events in RA
      patients. After exclusion of the studies not fulfilling our inclusion criteria
      four studies were finally analyzed. The total number of RA patients included in
      these studies was 4896. RESULTS: Statins were associated with reduced CV events
      and mortality in RA in primary prevention but not in secondary prevention. In
      secondary prevention after myocardial infarction (MI) there was no statistically
      significant difference between RA or non-RA patients either receiving
      atorvastatin 80 mg or simvastatin 20-40 mg daily. Treatment with atorvastatin 80
      mg led to a reduction in overall risk of CV disease in both patients with and
      without inflammatory joint disease compared to patients receiving the
      conventional/low-dose statin treatment. Statin discontinuation in RA patients was
      associated with an increased risk of acute myocardial infarction or CV mortality.
      Myalgia, diarrhoea, abdominal pain and nausea may be more frequent in RA patients
      than in controls. CONCLUSION: The published evidence shows that in RA patients
      statin treatment appears to reduce CV risk in primary prevention and that statin
      discontinuation is associated with an increased risk for CV events. However, the
      significance of statin treatment in RA patients still remains unclear as only
      very little evidence has been published. Whether all RA patients would benefit
      from treatment with statins still needs to be investigated.

PMID- 24931357
TI  - Systemic toxic effects during early phases of topical 4-NQO-induced oral
      carcinogenesis in rats.
AB  - BACKGROUND: Most studies have demonstrated 4-NQO toxicity to oral epithelium
      during oral carcinogenesis induction, but systemic toxicity has been poorly
      addressed. The aim of this study was to describe the systemic effect of 4-NQO
      topical application during early phases of oral cancer induction. METHODS: A 4
      NQO propylene glycol ointment was topically applied on the rat tongue three times
      a week for 16 weeks. Local and systemic 4-NQO toxicity was evaluated by body
      weight gain, hematology, and serum chemistry analyses, histopathology, and
      proliferating cell nuclear antigen (PCNA) immunohistochemistry. RESULTS:
      Significant reduction in body weight gain and in white blood cell count as well
      as significant increase in serum ALT and AST was observed after 16 weeks of 4-NQO
      topical application. Focal hepatic lobular necrosis, renal tubular degeneration,
      and decreased cellularity in the splenic white pulp were also detected.
      CONCLUSIONS: 4-NQO topical application on the tongue of rats for 16 weeks seems
      to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity
      should be considered to monitor for variables that could interfere in topical
      oral carcinogenesis experiments.

PMID- 24931359
TI  - Multiple exciton generation in cluster-free alloy Cd(x)Hg(1-x)Te colloidal
      quantum dots synthesized in water.
AB  - A number of different composition CdxHg1-xTe alloy quantum dots have been
      synthesized using a modified aqueous synthesis and ion exchange method. The
      benefits of good stoichiometric control and high emission quantum yield were
      retained whilst also ensuring that the tendency to form gel-like clusters and
      adsorb excess cations in the stabilizing ligand shells was mitigated using a
      sequestering method to remove excess ionic material during and after the
      synthesis. This was highly desirable for ultrafast carrier dynamics measurements,
      avoiding strong photocharging effects which may mask fundamental carrier signals.
      Transient grating measurements revealed a composition dependent carrier
      multiplication process which competes with phonon mediated carrier cooling to
      deplete the initial hot carrier population. The interplay between these two
      mechanisms is strongly dependent on the electron effective mass which in these
      alloys has a marked composition dependence and may be considerably lower than the
      hole effective mass. For a composition x = 0.52 we measured a maximum carrier
      multiplication quantum yield of 199 +/- 19% with pump photon energy 3 times the
      bandgap energy, Eg, whilst the threshold energy is calculated to be just 2.15Eg.
      There is some evidence to suggest an impact ionization process analogous to the
      inverse Auger S mechanism seen in bulk CdxHg1-xTe. 

PMID- 24931358
TI  - The health status of people claiming compensation for musculoskeletal injuries
      following road traffic crashes is not altered by an early intervention programme:
      a comparative study.
AB  - OBJECTIVE: To compare health outcomes among claimants compared to those who were
      ineligible or choose not to lodge a compensation claim. We also evaluated the
      effect of an early intervention programme on the health outcomes of the
      participants. DESIGN: Prospective comparative study using sequential cohorts.
      SUBJECTS: People presenting to hospital emergency departments with mild to
      moderate musculoskeletal injuries following road traffic crashes. INTERVENTION:
      referral to an early intervention programme for assessment by musculoskeletal
      physician, pain management education, promotion of self-management and
      encouragement of early activity. MAIN OUTCOMES: The 36-Item Short-Form Survey (SF
      36); Hospital Anxiety and Depression Scale (HADS) and Functional Rating Index
      (FRI) scores were assessed at post-crash and at 12 months. RESULTS: At 12 months,
      mean scores in six and five of the SF-36 domains were significantly lower among
      participants who claimed compensation versus those who chose not to claim or were
      ineligible, respectively. Differences in mean SF-36 scores ranged from 3.0
      ('general health perception') to 8.0 units ('role limitations due to physical
      problems'). Participants who claimed compensation had 6.3- and 4.6-units lower SF
      36 physical component score compared to those who were ineligible (p=0.001) or
      chose not to claim (p=0.01), respectively. Participants who claimed compensation
      reported a worse HADS-depression score of 6.46 versus 4.97 and 4.69 observed in
      those who were ineligible (p=0.04) or did not claim (p=0.01). Claimants had worse
      FRI scores compared to non-claimants (p=0.01) and those who were ineligible
      (p=0.01). The early intervention did not improve health outcomes, 12 months after
      injury. CONCLUSIONS: Claiming compensation was associated with a worse health
      status for people with soft tissue injuries caused by road traffic crashes. The
      health status in people claiming compensation was not altered by an early
      intervention programme.

PMID- 24931360
TI  - 1,2,3-Triazolylidene ruthenium(II)(eta6-arene) complexes: synthesis, metallation
      and reactivity.
AB  - Three bis(1,2,3-triazolylidene) silver(I) complexes were synthesized, and the
      ruthenium complexes ([RCH2N2(NMe)C2Ph)]RuCl2(p-cymene) (R = C6H2Me3 4a1, C6H2iPr3
      4b1) were isolated as major products with the minor C(sp(2))-H activated products
      ([RCH2N2(NMe)C2C6H4)]RuCl(p-cymene) (R = C6H2Me3 4a2, C6H2iPr3 4b2). In the
      related case where R = Ph, the species ([PhCH2N2(NMe)C2Ph)]RuCl2(p-cymene) 4c1
      was obtained with two C(sp(2))-H activated products [PhCH2N2(NMe)C2C6H4)]RuCl(p
      cymene) 4c2 and [(C6H4)CH2N2(NMe)C2Ph)]RuCl(p-cymene) 4c3 derived from
      metallation of the N and C-bound arene rings. Heating a solution of 4a1 at 45 
      degrees C over three weeks resulted in a ruthenium(II)(1,2,3-triazolylidene)
      complex [(C6H2Me3)CH2N2(NMe)C2Ph)]RuCl2 5a, where the pendant mesityl group on
      the triazolylidene moiety displaced the p-cymene ligand. The complexes 4a1, 4b1,
      4c1 and 5a displayed moderate catalytic activities in base-free oxidation of
      benzyl alcohols to benzaldehydes and oxidative homocoupling of benzyl amines to
      imines using oxygen as oxidant.

PMID- 24931361
TI  - Activation of integrin beta1 mediates the increased malignant potential of
      ovarian cancer cells exerted by inflammatory cytokines.
AB  - Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy since
      it could not be discovered until at late stage. Identifying the molecular
      phenotype alteration during the development and progression of ovarian cancer is
      an urgent demand for the targeted intervention therapy. Recently, inflammation
      and Integrin beta 1(ITGB1), a subunit of heterodimeric transmembrane receptors
      family, had been pointed out to be involved in promoting ovarian tumorigenesis
      and cancer progression, respectively. However, the relationship between ITGB1 and
      the inflammatory mediators in ovarian cancer progression remains obscure. In the
      present study, ITGB1 was observed to be frequently upregulated in ovarian cancer,
      overexpression of ITGB1 led to a more invasive and mesenchymal phenotype.
      Furthermore, our results also provided evidence concerning the role of
      inflammatory cytokines (IL-6, TGF-beta1 and SDF-1) in ITGB1 expression as well as
      in the malignant potential of ovarian cancer cells. Consistently, sh-RNA mediated
      knocking down of ITGB1 evidently reduced tumor growth and peritoneal
      dissemination in in vivo Nod-scid SKOV3 orthotopic xenograft mice. Overall, the
      present data suggested that ITGB1 upregulation was involved in the regulation of
      tumorigenesis and disease exacerbation exerted by inflammatory cytokines as IL-6,
      TGF-beta1 and SDF-1, and suggested that targeting ITGB1 and the underlying
      inflammatory modulator was an attractive strategy for therapeutic intervention
      during ovarian carcinogenesis.

PMID- 24931362
TI  - Oocyte vitrification in the 21st century and post-warming fertility outcomes: a
      systematic review and meta-analysis.
AB  - Oocyte cryopreservation is a rapidly developing technology, which is increasingly
      being used for various medical, legal and social reasons. There are
      inconsistencies in information regarding survival rate and fertility outcomes.
      This systematic review and meta-analysis provides evidence-based information
      about oocyte survival and fertility outcomes post warming to help women to make
      informed choices. All randomized and non-randomized, controlled and prospective
      cohort studies using oocyte vitrification were included. The primary outcome
      measure was ongoing pregnancy rate/warmed oocyte. Sensitivity analysis for donor
      and non-donor oocyte studies was performed. Proportional meta-analysis of 17
      studies, using a random-effects model, showed pooled ongoing pregnancy and
      clinical pregnancy rates per warmed oocyte of 7%. Oocyte survival, fertilization,
      cleavage, clinical pregnancy and ongoing pregnancy rates per warmed oocyte were
      higher in donor versus non-donor studies. Comparing vitrified with fresh oocytes,
      no statistically significant difference was observed in fertilization, cleavage
      and clinical pregnancy rates, but ongoing pregnancy rate was reduced in the
      vitrified group (odds ratio 0.74), with heterogeneity between studies.
      Considering the age of women and the reason for cryopreservation, reasonable
      information can be given to help women to make informed choices. Future studies
      with outcomes from oocytes cryopreserved for gonadotoxic treatment may provide
      more insight. 

PMID- 24931363
TI  - Large-scale solution-phase production of Bi2Te3 and PbTe nanowires using Te
      nanowire templates.
AB  - We report the first demonstration of large scale (>10 g) and high yield (>80%)
      production of ultrathin (<15 nm) PbTe and Bi2Te3 nanowires in a low-cost solution
      based process using Te nanowire templates. The PbTe or Bi2Te3 nanowires can be
      compressed into high relative density disks with nanoscale grains.

PMID- 24931364
TI  - Dermoscopic features of congenital acral melanocytic naevi in children: a
      prospective comparative and follow-up study.
AB  - BACKGROUND: Acral naevi are a peculiar subtype of naevus with specific
      dermoscopic patterns. Little is known about congenital melanocytic naevi
      affecting acral volar skin in children. OBJECTIVES: To determine the dermoscopic
      features of acquired and congenital acral melanocytic naevi in children and to
      assess their key differences in this age group. METHODS: This was a prospective
      observational controlled study conducted in two outpatient dermatology university
      hospitals in Nice, France. We recruited 24 children with 24 congenital acral
      melanocytic naevi (CAMNs) and 26 children with 33 acquired acral melanocytic
      naevi (AAMNs), and determined the clinical and dermoscopic features of both.
      Images were evaluated and compared by two dermatologists. Fourteen patients with
      CAMN were followed up. RESULTS: CAMNs were larger, and more asymmetrical and
      comma shaped than AAMNs. The parallel furrow pattern was predominant in CAMN
      (75%) and AAMN (79%). Globules were more frequent in CAMN (88%) than in AAMN
      (61%) (P = 0.026), often with a 'pearl necklace' distribution along skin
      markings. Central blue-grey pigmentation was present in 50% of CAMNs vs. 9% of
      AAMNs (P = 0.001). A new dermoscopic feature of central enlarged pink ridges was
      observed in 54% of CAMNs vs. 6% of AAMNs (P < 0.001). The follow-up of CAMNs did
      not reveal the appearance of dermoscopic features of melanoma. CONCLUSIONS: CAMNs
      in children have specific features compared with AAMNs. Our results suggest that
      small CAMNs need not be excised, but should be followed up.

PMID- 24931365
TI  - Eosinophilic esophagitis in children following cardiac transplantation:
      association with post-transplant lymphoproliferative disorder and other
      transplant outcomes.
AB  - Although cardiac transplantation is life-saving, morbidities from
      immunosuppression are significant. EoE is a complication of calcineurin
      inhibitors following liver transplant causing feeding intolerance, weight loss,
      vomiting, and dysphagia. There are limited reports of EoE following heart
      transplantation. We performed a retrospective single-center review of pediatric
      cardiac transplant patients from 2000 to 2010. A case-control analysis of
      patients with and without EoE was performed evaluating heart transplantation
      outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty-six
      transplants were performed in 84 patients; 34 (40%) underwent diagnostic
      endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7 yr (IQR:
      2.0-5.2). There were no differences in demographics or use of induction
      medications between patients with or without EoE. Patients with EoE had fewer
      episodes of treated rejection (1.0 vs. 2.5; p = 0.04). Four of 10 (40%) EoE
      patients had PTLD compared with only 2/24 (8%) of those without EoE (p = 0.048;
      OR 7.33 [95% CI: 1.1-50.2]). There were no differences in CAV or graft loss
      between groups. EoE should be considered as a cause of GI symptoms in children
      after cardiac transplantation and may be associated with fewer rejection episodes
      and increased rates of PTLD, thus representing a marker of over
      immunosuppression. 

PMID- 24931366
TI  - A new model of the role of psychological and emotional distress in promoting
      obesity: conceptual review with implications for treatment and prevention.
AB  - The lack of significant treatment and prevention progress highlights the need for
      a more expanded strategy. Given the robust association between socioeconomic
      factors and obesity, combined with new insights into how socioeconomic
      disadvantage affects both behaviour and biology, a new causal model is proposed.
      The model posits that psychological and emotional distress is a fundamental link
      between socioeconomic disadvantage and weight gain. At particular risk are
      children growing up in a disharmonious family environment, mainly caused by
      parental socioeconomic disadvantage, where they are exposed to parental
      frustrations, relationship discord, a lack of support and cohesion, negative
      belief systems, unmet emotional needs and general insecurity. Without adequate
      resilience, such experiences increase the risk of psychological and emotional
      distress, including low self-esteem and self-worth, negative emotions, negative
      self-belief, powerlessness, depression, anxiety, insecurity and a heightened
      sensitivity to stress. These inner disturbances eventually cause a psycho
      emotional overload, triggering a cascade of weight gain-inducing effects
      including maladaptive coping strategies such as eating to suppress negative
      emotions, chronic stress, appetite up-regulation, low-grade inflammation and
      possibly reduced basal metabolism. Over time, this causes obesity, circular
      causality and further weight gain. Tackling these proposed root causes of weight
      gain could potentially improve both treatment and prevention outcomes. 

PMID- 24931367
TI  - Pctaire1/Cdk16 promotes skeletal myogenesis by inducing myoblast migration and
      fusion.
AB  - The Cdk-related protein kinase Pctaire1/Cdk16 is abundantly expressed in brain,
      testis and skeletal muscle. Functional roles of Pctaire1 such as regulation of
      neuron migration and neurite outgrowth thus far have been mainly elucidated in
      the field of nervous system development. Although these regulations based on
      cytoskeletal rearrangements evoke a possible role of Pctaire1 in the development
      of skeletal muscle, little is known in this regard. In this study, we
      demonstrated that myogenic differentiation and subsequent fusion is promoted in
      Pctaire1 overexpressing cells, and conversely, is inhibited in the knockdown
      cells. Furthermore, our findings suggest that Pctaire1 exerts promyogenic effects
      by regulating myoblast migration and process formation during skeletal
      myogenesis. 

PMID- 24931368
TI  - Paris. Editorial.

PMID- 24931369
TI  - Activation of TRPV1 mediates thymic stromal lymphopoietin release via the
      Ca2+/NFAT pathway in airway epithelial cells.
AB  - The airway epithelium is exposed to a range of irritants in the environment that
      are known to trigger inflammatory response such as asthma. Transient receptor
      potential vanilloid 1 (TRPV1) is a Ca(2+)-permeable cation channel critical for
      detecting noxious stimuli by sensory neurons. Recently increasing evidence
      suggests TRPV1 is also crucially involved in the pathophysiology of asthma on
      airway epithelium in human. Here we report that in airway epithelial cells TRPV1
      activation potently induces allergic cytokine thymic stromal lymphopoietin (TSLP)
      release. TSLP induction by protease-activated receptor (PAR)-2 activation is also
      partially mediated by TRPV1 channels. 

PMID- 24931370
TI  - miR-96/HBP1/Wnt/beta-catenin regulatory circuitry promotes glioma growth.
AB  - We found that miR-96 is overexpressed in glioma, and its level inversely
      correlates with the survival of patients. The reduction in miR-96 abundance
      suppresses the proliferation and colony formation of glioma cells. The
      tumorigenicity of U-87 MG cells is reduced by miR-96 silencing. miR-96
      contributes to the activation of Wnt/beta-catenin pathway in glioma cells. HMG
      box transcription factor 1 (HBP-1), a Wnt/beta-catenin pathway inhibitor, is
      suppressed by miR-96. The reactivation of Wnt/beta-catenin signaling causes an
      increase in the proliferation of glioma cells, and a decrease in miR-96
      expression. On the other hand, HBP1 silencing promotes miR-96 expression.
      Collectively, miR-96 contributes to the progression of glioma by enhancing the
      activation of the Wnt/beta-catenin pathway, and the miR-96/HBP1/Wnt/beta-catenin
      regulatory circuitry promotes the proliferation of glioma cells. 

PMID- 24931372
TI  - Insight into the molecular interaction between the cyclic nucleotide-binding
      homology domain and the eag domain of the hERG channel.
AB  - The gating of the hERG channel is regulated by its eag domain through molecular
      interaction with either the cyclic nucleotide-binding homology domain (CNBHD) or
      the linker between transmembrane segments 4 and 5. Our NMR study on the purified
      CNBHD demonstrated that it contains nine beta-strands and does not bind cAMP. We
      show that the eag domain binds to the CBND through an interface containing
      several disease-associated mutations. The N-terminal cap domain and R56 in the
      eag domain are important for the interaction with the CNBHD. Residues from the
      CNBHD that were affected by the interaction with the eag domain were also
      identified. A R56Q mutation does not cause major structural changes in the eag
      domain and showed reduced interaction with the CNBHD. 

PMID- 24931371
TI  - Membrane protein synthesis in cell-free systems: from bio-mimetic systems to bio
      membranes.
AB  - When taking up the gauntlet of studying membrane protein functionality,
      scientists are provided with a plethora of advantages, which can be exploited for
      the synthesis of these difficult-to-express proteins by utilizing cell-free
      protein synthesis systems. Due to their hydrophobicity, membrane proteins have
      exceptional demands regarding their environment to ensure correct functionality.
      Thus, the challenge is to find the appropriate hydrophobic support that
      facilitates proper membrane protein folding. So far, various modes of membrane
      protein synthesis have been presented. Here, we summarize current state-of-the
      art methodologies of membrane protein synthesis in biomimetic-supported systems.
      The correct folding and functionality of membrane proteins depend in many cases
      on their integration into a lipid bilayer and subsequent posttranslational
      modification. We highlight cell-free systems utilizing the advantages of
      biological membranes. 

PMID- 24931373
TI  - A possible iron delivery function of the dinuclear iron center of HcgD in [Fe]
      hydrogenase cofactor biosynthesis.
AB  - HcgD, a homolog of the ubiquitous Nif3-like protein family, is found in a gene
      cluster involved in the biosynthesis of the iron-guanylylpyridinol (FeGP)
      cofactor of [Fe]-hydrogenase. The presented crystal structure and biochemical
      analyses indicated that HcgD has a dinuclear iron-center, which provides a
      pronounced binding site for anionic ligands. HcgD contains a stronger and a
      weaker bound iron; the latter being removable by chelating reagents
      preferentially in the oxidized state. Therefore, we propose HcgD as an iron
      chaperone in FeGP cofactor biosynthesis, which might also stimulate
      investigations on the functionally unknown but physiologically important
      eukaryotic Nif3-like protein family members. 

PMID- 24931374
TI  - Wheat germ systems for cell-free protein expression.
AB  - Cell-free protein expression plays an important role in biochemical research.
      However, only recent developments led to new methods to rapidly synthesize
      preparative amounts of protein that make cell-free protein expression an
      attractive alternative to cell-based methods. In particular the wheat germ system
      provides the highest translation efficiency among eukaryotic cell-free protein
      expression approaches and has a very high success rate for the expression of
      soluble proteins of good quality. As an open in vitro method, the wheat germ
      system is a preferable choice for many applications in protein research including
      options for protein labeling and the expression of difficult-to-express proteins
      like membrane proteins and multiple protein complexes. Here I describe wheat germ
      cell-free protein expression systems and give examples how they have been used in
      genome-wide expression studies, preparation of labeled proteins for structural
      genomics and protein mass spectroscopy, automated protein synthesis, and
      screening of enzymatic activities. Future directions for the use of cell-free
      expression methods are discussed. 

PMID- 24931376
TI  - Single-enzyme kinetics with fluorogenic substrates: lessons learnt and future
      directions.
AB  - Single-molecule fluorescence techniques have developed into powerful tools for
      studying the kinetics of biological reactions at the single-molecule level. Using
      fluorogenic substrates, enzymatic reactions can be observed in real-time with
      single-turnover resolution. The turnover sequence contains all kinetic
      information, giving access to reaction substeps and dynamic processes such as
      fluctuations in the reaction rate. Despite their clearly proven potential, the
      accuracy of current measurements is limited by the availability of substrates
      with 1:1 stoichiometry and the signal-to-noise ratio of the measurement. In this
      review we summarize the state-of-the-art and discuss these limitations using
      experiments performed with alpha-chymotrypsin as an example. We are further
      providing an overview of recent efforts aimed at the improvement of fluorogenic
      substrates and the development of new detection schemes. These detection schemes
      utilize nanophotonic structures such as zero mode waveguides or nanoantennas.
      Nanophotonic approaches reduce the size of the effective detection volume and are
      a powerful strategy to increase the signal-to-noise ratio. We believe that a
      combination of improved substrates and novel detection schemes will pave the way
      for performing accurate single-enzyme experiments in biologically relevant
      conditions. 

PMID- 24931375
TI  - The architect who never sleeps: tumor-induced plasticity.
AB  - Tumor cell plasticity is an event that has been observed in several malignancies.
      In fact, most of the solid tumors are characterized by cellular heterogeneity and
      undergo constant changes as the tumor develops. The increased plasticity
      displayed by these cells allows them to acquire additional properties, enabling
      epithelial-mesenchymal transitions, dedifferentiation and the acquisition of stem
      cell-like properties. Here we discuss the particular importance of an
      inflammatory microenvironment for the bidirectional control of cellular
      plasticity and the potential for therapeutic intervention. 

PMID- 24931377
TI  - An inhibition model of BPTI to unlinked dengue virus NS2B-NS3 protease.
AB  - One approach to treating the dengue virus infection is to inhibit its NS2B-NS3
      protease that plays a vital role in virus maturation. However, the lack of
      structural information on the active conformation of the protease hindered
      related drug design. With a co-expression system, we obtained the active two
      component protease in its unlinked form. BPTI shows strong competitive inhibitory
      activity (Ki = 6.5 nM) against this unlinked protease, which adopts a closed
      conformation. Based on the biochemical and NMR perturbation information, an
      inhibition model of BPTI to NS2B-NS3 protease is proposed.

PMID- 24931378
TI  - The emerging age of cell-free synthetic biology.
AB  - The engineering of and mastery over biological parts has catalyzed the emergence
      of synthetic biology. This field has grown exponentially in the past decade. As
      increasingly more applications of synthetic biology are pursued, more challenges
      are encountered, such as delivering genetic material into cells and optimizing
      genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology
      simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this
      review, we describe some of the innate features that make cell-free systems
      compelling platforms for synthetic biology and discuss emerging improvements of
      cell-free technologies. We also select and highlight recent and emerging
      applications of cell-free synthetic biology. 

PMID- 24931379
TI  - Conformable GORE TAG thoracic endoprosthesis.
AB  - US FDA approval of the conformable Gore TAG thoracic endoprosthesis for multiple
      indications including aneurysm, traumatic transection and Type B dissection marks
      significant progress in minimally invasive therapies for the treatment of
      complex, life-threatening thoracic aortic pathology. This second generation
      device, with its enhanced flexibility and conformability, is providing
      improvements in both short- and long-term outcomes for many patients who may
      otherwise be denied life-saving treatment for thoracic aortic pathology. 

PMID- 24931380
TI  - Prehospital management of supraventricular tachycardia in Victoria, Australia:
      epidemiology and effectiveness of therapies.
AB  - OBJECTIVE: The present study examined patient demographics, characteristics and
      the effectiveness of current prehospital supraventricular tachycardia (SVT)
      management by ambulance paramedics in Victoria, Australia. METHOD: We conducted a
      retrospective study of all Victorian patients attended by paramedics between 14
      February 2012 and 13 February 2013, where SVT was the initial or final diagnosis.
      Patients were excluded if SVT was not captured on ECG, incomplete data were
      recorded, or SVT began after initial assessment. Data were extracted from the
      VACIS((r)) clinical data warehouse. Accuracy of paramedic SVT diagnosis was
      examined. RESULTS: Nine hundred and thirty-three patients were enrolled,
      including 882 (94.5%) adults and 564 (60.5%) women. Mean adult and paediatric
      (<18 years) patient ages were 57.5 (SD 18.1) and 10.0 (SD 4.5) years,
      respectively. Median ambulance response time was 11.0 (IQR 8.0) min. Paramedics
      correctly identified SVT in 119/123 (96.7%, 95% CI: 91.5, 99.0) of adult ECG
      strips examined. There were 273/882 (31.0%) patients who spontaneously reverted
      while in paramedic care. Valsalva manoeuvre was undertaken by 212/882 (24.0%)
      patients and reverted the SVT in 99/358 (27.7%) attempts. Verapamil was
      administered to 38/882 (4.3%) patients and reverted 33 (86.8%). Aramine was
      administered to 43/882 (4.9%) patients and 35 reverted following administration
      (81.4%). Synchronised cardioversion (70 J) reverted four patients at first
      attempt. Ultimately, 438 (49.7%) patients remained in SVT on arrival at hospital.
      CONCLUSION: Patient characteristics associated with SVT are more likely to be
      middle-aged women with a history of hypertension and hypercholesterolaemia.
      Therapies were underutilised leading to reduced clinical guideline effectiveness.
      Where therapies were instigated, reversion rates are greater than previously
      reported.

PMID- 24931381
TI  - Re. 'Abdominal hypertension and decompression: the effect on peritoneal
      metabolism in an experimental porcine study'.

PMID- 24931382
TI  - Response to letter to the editor Re "Abdominal hypertension and decompression:
      the effect on peritoneal metabolism in an experimental porcine study".

PMID- 24931383
TI  - Computed tomography for the diagnosis of solitary thin-walled cavity lung cancer.
AB  - BACKGROUND AND AIM: Lung cancer is the most commonly diagnosed neoplasm and the
      leading cause of cancer-related death worldwide. Despite the high incidence of
      lung cancer, the diagnosis of solitary thin-walled cavity lung cancer is rare.
      The aim of this review is to explore the potentials of computed tomography (CT)
      as diagnostic tool for solitary thin-walled cavity lung cancer. METHOD: The
      literature search was made in electronic databases including PudMed, Ovid SP,
      Embase, Web of Sciences, EBSCO and Wiley online by using relevant key terms.
      Because of the rarity of the subject, no precise exclusion or inclusion criteria
      were used for article selection and the outcome dissemination was decided to be
      more descriptive rather than quantitative. RESULTS: The detection of cavitation
      in lungs is frequently done utilizing chest radiographs CT scans. However, the
      diagnostic challenge remains the accurate detection of solitary thin-walled
      cavity lung cancer among the prevalence of cavitary lung lesions in multiple
      thoracic disorders including benign disorders, infectious disease and malignant
      tumors. Moreover, an accurate diagnosis of solitary thin-walled cavity lung
      cancer is further complicated by its subjective classification within the
      literature. In order to facilitate early diagnosis of this disease and circumvent
      the need for more invasive tests that may not be warranted, the overarching goal
      is to establish definitive radiological features of lung cavities that are
      indicative of malignancy. Herein, we describe the benefits of using CT to
      identify and diagnose solitary thin-walled cavity lung cancer, as well as explore
      the underlying mechanisms that contribute to thin-walled cavity formation in
      oncology patients. CONCLUSION: CT is the best modality for the noninvasive
      differentiation between malignant and nonmalignant cavities as it provides
      reliable information regarding the morphology and density of lesions. Besides, CT
      densitometry can efficiently detect the calcifications in lesions.

PMID- 24931384
TI  - Discovery of 4-aryl-7-hydroxyindoline-based P2Y1 antagonists as novel
      antiplatelet agents.
AB  - Adenosine diphosphate (ADP)-mediated platelet aggregation is signaled through two
      distinct G protein-coupled receptors (GPCR) on the platelet surface: P2Y12 and
      P2Y1. Blocking P2Y12 receptor is a clinically well-validated strategy for
      antithrombotic therapy. P2Y1 antagonists have been shown to have the potential to
      provide equivalent antithrombotic efficacy as P2Y12 inhibitors with reduced
      bleeding in preclinical animal models. We have previously reported the discovery
      of a potent and orally bioavailable P2Y1 antagonist, 1. This paper describes
      further optimization of 1 by introducing 4-aryl groups at the hydroxylindoline in
      two series. In the neutral series, 10q was identified with excellent potency and
      desirable pharmacokinetic (PK) profile. It also demonstrated similar
      antithrombotic efficacy with less bleeding compared with the known P2Y12
      antagonist prasugrel in rabbit efficacy/bleeding models. In the basic series, 20c
      (BMS-884775) was discovered with an improved PK and liability profile over 1.
      These results support P2Y1 antagonism as a promising new antiplatelet target. 

PMID- 24931385
TI  - Zeolites are no longer a challenge: atomic resolution data by aberration
      corrected STEM.
AB  - Transmission electron microscopy is undoubtedly an indispensable tool for
      materials characterization, which can currently reach sub-angstrom resolution
      down to the elemental building blocks of matter, isolated single atoms of most
      elements. In addition to the phenomenal image resolution, if the material is
      strong enough, it can be accompanied with chemical information, converting
      electron microscopy into a unique method for the analysis of a great variety of
      materials. Unfortunately, extracting all this valuable information is not simple
      as most materials in one way or another are affected by the strong and localized
      electron beam. Radiolysis is one kind of reaction between electrons and matter
      than can cause irreversible structural transformations in our materials. This
      effect is the predominant factor in zeolites, zeotypes and the majority of
      molecular sieves. In the present work some results, taken at high voltage (300
      kV) and minimizing the exposure to the beam, are presented proving the
      feasibility of the technique to obtain unprecedented atomic resolution
      information of different zeolites and microporous solids.

PMID- 24931386
TI  - Electron-induced Ti-rich surface segregation on SrTiO3 nanoparticles.
AB  - Atomic surface structures of nanoparticles are of interest in catalysis and other
      fields. Aberration-corrected HREM facilitates direct imaging of the surfaces of
      nanoparticles. A remaining concern of surface imaging arises from beam damage. It
      is important to identify the intrinsic surface structures and the ones created by
      electron beam irradiation in TEM. In this study, we performed aberration
      corrected HREM and EELS to demonstrate that TiO and bcc type Ti islands form due
      to intense electron irradiation. The formation of Ti-rich islands is in agreement
      with previous high temperature annealing experiments on the surfaces of SrTiO3
      single crystals. 

PMID- 24931387
TI  - Uncovering alternate charge transfer mechanisms in Escherichia coli chemically
      functionalized with conjugated oligoelectrolytes.
AB  - Conjugated oligoelectrolytes integrated in Escherichia coli have been proposed to
      act as 'molecular wires', inducing extracellular electron transfer. This is
      monitored through reduction of HAuCl4 to form gold nanoparticles. In contrast to
      direct electron transfer, the reduction mechanism was traced to the release of
      electroactive cytosolic components during oligoelectrolyte incorporation. 

PMID- 24931388
TI  - Improved high-speed capillary electrophoresis system using a short capillary and
      picoliter-scale translational spontaneous injection.
AB  - Here, we describe an improved high-speed CE (HSCE) system using a short capillary
      and translational spontaneous sample injection. Several important factors for
      consideration in system design as well as various factors influencing the
      performance of the HSCE system were investigated in detail. The performance of
      this HSCE system was demonstrated in electrophoretic separation of FITC-labeled
      amino acids. Under optimized conditions, baseline separation of eight amino acids
      and FITC were achieved in 21 s with the plate heights ranging from 0.20 to 0.31
      MUm, corresponding to a separation rate up to 20 700 theoretical plates per
      second. The separation speed and efficiency of the optimized high-speed CE system
      are comparable to or even better than those reported in microchip-based CE
      systems. 

PMID- 24931389
TI  - Insulin regulates primordial-follicle assembly in vitro by affecting germ-cell
      apoptosis and elevating oestrogen.
AB  - Insulin is a protein secreted by pancreatic beta-cells, which plays an important
      role in the regulation of ovarian function. However, the specific molecular
      mechanism of its function remains largely unknown. This study aimed to assess the
      effect of insulin on mouse folliculogenesis using an in vitro ovary-culture
      model. The results demonstrated that insulin promoted the proliferation of
      ovarian granulosa cells in vitro, and thereby accelerated the progress of
      folliculogenesis (the percentage of oocytes in cysts declined from 42.6% to
      29.3%); however, the percentage of apoptotic oocytes increased after insulin
      treatment. Further investigation indicated that apoptosis occurred mainly in germ
      cell cysts. After 3 days of insulin treatment, oestrogen in the culture medium of
      mouse ovaries significantly increased (P<0.01), while the lower dose of oestrogen
      promoted primordial-follicle assembly in vitro. In conclusion, insulin promoted
      folliculogenesis by facilitating germ-cell apoptosis within the cysts and
      upregulating oestrogen levels. 

PMID- 24931390
TI  - Theoretical and experimental investigation of fluid rheology effects on modulated
      ultrasound propagation.
AB  - A mathematical model is developed and presented to capture the effect of
      viscoelastic nature of a material on modulated ultrasound (US) pulses. The model
      is established by considering perturbation of material elements subject to
      modulated US pulses and by introducing the exponential relaxation of the
      perturbed fluid elements with a spectrum of time constants. Both the model and
      experimental findings revealed that consecutive perturbation of a material via
      the modulated US pulses enabled to probe the relaxation times of similar order of
      magnitudes to the frequency of the US modulation while filtering out the impact
      of other relaxation times on the US measurement. The US experimental results were
      verified by those of a conventional rheometer. Hence carrying out measurements at
      different US modulation frequencies in the Hz ranges seems to allow one to obtain
      the relaxation time spectrum of the investigated material in the time scales of
      milliseconds to seconds. 

PMID- 24931392
TI  - Narcolepsy: let the patient's voice awaken us!

PMID- 24931391
TI  - 17beta-estradiol regulates giant vesicle formation via estrogen receptor-alpha in
      human breast cancer cells.
AB  - A significant proportion of the genes regulated by 17-beta-estradiol (E2) via
      estrogen receptor alpha (ERalpha) have roles in vesicle trafficking in breast
      cancer. Intracellular vesicle trafficking and extracellular vesicles have
      important roles in tumourigenesis. Here we report the discovery of giant (3
      42MUm) intracellular and extracellular vesicles (GVs) and the role of E2 on
      vesicle formation in breast cancer (BC) cell lines using three independent live
      cell imaging techniques. Large diameter vesicles, GVs were also identified in a
      patient-derived xenograft BC model, and in invasive breast carcinoma tissue.
      ERalpha-positive (MCF-7 and T47D) BC cell lines demonstrated a significant
      increase in GV formation after stimulation with E2 which was reversed by
      tamoxifen. ERalpha-negative (MDA-MB-231 and MDA-MB-468) BC cell lines produced
      GVs independently of E2 and tamoxifen. These results indicate the existence of
      both intracellular and extracellular vesicles with considerably larger dimensions
      than generally recognised with BC cells and suggest that the GVs are regulated by
      E2 via ERalpha in ERalpha-positive BC but by E2-independent mechanisms in ER-ve
      BC. 

PMID- 24931393
TI  - New-onset atrial fibrillation predicts heart failure progression.
AB  - BACKGROUND: Atrial fibrillation and heart failure with reduced left ventricular
      ejection fraction have interrelated pathophysiologies. New-onset atrial
      fibrillation in heart failure patients has been associated with increased
      mortality, but has not been definitively related to clinical heart failure
      progression. METHODS: To test the hypothesis that new-onset atrial fibrillation
      is related to clinical heart failure progression, in 2392 patients without atrial
      fibrillation at randomization in the Beta-blocker Evaluation of Survival Trial we
      measured clinical endpoints in patients who did (Group 1, n = 190) or did not
      (Group 2, n = 2202) develop new-onset atrial fibrillation. Results were also
      compared with the 303 patients who entered the trial in atrial fibrillation
      (Baseline/chronic group), and in Group 1/2 patients we conducted a multivariate
      analysis of covariates potentially related to time to first heart failure
      hospitalization. RESULTS: Compared with Group 2, Group 1 patients post atrial
      fibrillation onset had a ~2-fold increase in mortality (P < .0001) and a ~4.5
      fold increase in all-cause or heart failure hospitalization days/patient
      (hospitalization burden, both P < .0001). In Group 1, both types of
      hospitalization burden were 2.9-fold greater than in the Baseline/chronic group
      (P < .001), and hospitalization burden increased ~6-fold (P < .0001) compared
      with the pre-event period. On multivariate analysis, new-onset atrial
      fibrillation was a highly significant (P < .00001) predictor of heart failure
      hospitalization. CONCLUSIONS: In addition to being a discrete electrophysiologic
      event, in heart failure patients, new-onset atrial fibrillation is a predictor of
      and trigger for clinical heart failure progression.

PMID- 24931395
TI  - Risk factors for serious prescription opioid-related toxicity or overdose among
      Veterans Health Administration patients.
AB  - OBJECTIVE: Prescription opioid use and deaths related to serious toxicity,
      including overdose, have increased dramatically in the United States since 1999.
      However, factors associated with serious opioid-related respiratory or central
      nervous system (CNS) depression or overdose in medical users are not well
      characterized. The objective of this study was to examine the factors associated
      with serious toxicity in medical users of prescription opioids. DESIGN:
      Retrospective, nested, case-control analysis of Veterans Health Administration
      (VHA) medical, pharmacy, and health care resource utilization administrative
      data. SUBJECTS: Patients dispensed an opioid by VHA between October 1, 2010 and
      September 30, 2012 (N=8,987). METHODS: Cases (N=817) experienced life-threatening
      opioid-related respiratory/CNS depression or overdose. Ten controls were randomly
      assigned to each case (N=8,170). Logistic regression was used to examine
      associations with the outcome. RESULTS: The strongest associations were maximum
      prescribed daily morphine equivalent dose (MED)>= 100 mg (odds ratio [OR]=4.1,
      95% confidence interval [CI], 2.6-6.5), history of opioid dependence (OR=3.9, 95%
      CI, 2.6-5.8), and hospitalization during the 6 months before the serious toxicity
      or overdose event (OR=2.9, 95% CI, 2.3-3.6). Liver disease, extended-release or
      long-acting opioids, and daily MED of 20 mg or more were also significantly
      associated. CONCLUSIONS: Substantial risk for serious opioid-related toxicity and
      overdose exists at even relatively low maximum prescribed daily MED, especially
      in patients already vulnerable due to underlying demographic factors, comorbid
      conditions, and concomitant use of CNS depressant medications or substances.
      Screening patients for risk, providing education, and coprescribing naloxone for
      those at elevated risk may be effective at reducing serious opioid-related
      respiratory/CNS depression and overdose in medical users of prescription opioids.

PMID- 24931396
TI  - Are we altering the natural history of primary myelofibrosis?
AB  - Primary myelofibrosis (PMF) is a clonal hematologic malignancy with a variable
      disease course; survival ranges from months to years. Historically, only
      allogeneic hematopoietic stem cell transplantation (alloHSCT) has demonstrated an
      ability to alter the natural history of PMF, but high treatment-related mortality
      risks limit the utility of alloHSCT to a minority of patients with PMF or
      myelofibrosis secondary to other myeloproliferative neoplasms. The recent
      development of therapies that regulate the Janus kinase-signal transducer and
      activator of transcription signaling pathway has changed the treatment landscape
      from primarily palliative treatment to potential disease modification. 

PMID- 24931397
TI  - The role of proteoglycans in the reactive stroma on tumor growth and progression.
AB  - The stroma surrounding tumors can either restrict or promote tumor growth and
      progression, and both the cellular and non-cellular components of the stroma play
      an active role. The cellular components in the surrounding stroma include tumor
      associated fibroblasts, host tissue cells and immune cells. The non-cellular
      components, which form the extracellular matrix (ECM) scaffold, include
      proteoglycans, collagen, proteinases, growth factors and cytokines. For
      tumorigenesis to occur it is necessary for tumor cells to modify the surrounding
      stroma. Tumor cells have mechanisms for achieving this, such as co-opting
      fibroblasts and modifying the ECM they produce, degrading the surrounding ECM
      and/or synthesizing a favorable ECM to support invasion. Proteoglycans are an
      important component of the ECM and play an active role in tumor growth and
      progression. The expression and glycosylation patterns of proteoglycans are
      altered in the stroma surrounding tumors and these molecules may support or
      restrict tumor growth and progression depending on the type and stage of tumor.
      In the present review we discuss the difference between the tumor promoting and
      restricting stromal reactions surrounding tumors and the role proteoglycans play.

PMID- 24931398
TI  - Intraframework migration of tetrahedral atoms in a zeolite.
AB  - The transformation from a disordered into an ordered version of the zeolite
      natrolite occurs on prolonged heating of this material in the crystallizing
      medium, but not if the mother liquor is replaced by water or an alkaline
      solution. This process occurs for both aluminosilicate and gallosilicate
      analogues of natrolite. In cross experiments, the disordered Al-containing (or Ga
      containing) analogue is heated while in contact with the mother liquor of the
      opposite analogue, that is, the Ga-containing (or Al-containing) liquor.
      Therefore, strong evidence for the mechanism of the ordering process was
      obtained, which was thus proposed to proceed by intraframework migration of
      tetrahedral atoms without diffusion along the pores. Migration is first
      triggered, then fuelled by surface rearrangement through reactions with the
      mother liquor, and stops when an almost fully ordered state is attained.
      Classical dissolution-recrystallization and Ostwald ripening processes do not
      appear to be relevant for this phase transformation. 

PMID- 24931394
TI  - PGM3 mutations cause a congenital disorder of glycosylation with severe
      immunodeficiency and skeletal dysplasia.
AB  - Human phosphoglucomutase 3 (PGM3) catalyzes the conversion of N-acetyl
      glucosamine (GlcNAc)-6-phosphate into GlcNAc-1-phosphate during the synthesis of
      uridine diphosphate (UDP)-GlcNAc, a sugar nucleotide critical to multiple
      glycosylation pathways. We identified three unrelated children with recurrent
      infections, congenital leukopenia including neutropenia, B and T cell
      lymphopenia, and progression to bone marrow failure. Whole-exome sequencing
      demonstrated deleterious mutations in PGM3 in all three subjects, delineating
      their disease to be due to an unsuspected congenital disorder of glycosylation
      (CDG). Functional studies of the disease-associated PGM3 variants in E. coli
      cells demonstrated reduced PGM3 activity for all mutants tested. Two of the three
      children had skeletal anomalies resembling Desbuquois dysplasia: short stature,
      brachydactyly, dysmorphic facial features, and intellectual disability. However,
      these additional features were absent in the third child, showing the clinical
      variability of the disease. Two children received hematopoietic stem cell
      transplantation of cord blood and bone marrow from matched related donors; both
      had successful engraftment and correction of neutropenia and lymphopenia. We
      define PGM3-CDG as a treatable immunodeficiency, document the power of whole
      exome sequencing in gene discoveries for rare disorders, and illustrate the
      utility of genomic analyses in studying combined and variable phenotypes. 

PMID- 24931399
TI  - Predictors of early introduction of complementary feeding: longitudinal study.
AB  - BACKGROUND: Early introduction of complementary foods prior to 6 months of age
      may shorten breast-feeding duration and expose the infant to increased risk of
      morbidity and mortality. The aims of this study were to document the ages of
      complementary food introduction and to identify the determinants associated with
      early introduction of complementary feeding in Sichuan Province. METHODS: A
      prospective study on infant feeding practices was conducted during 2010-2011 in
      Jiangyou, China. A total of 695 mothers were recruited and interviewed at
      discharge. The follow-up interviews were carried out by telephone at 1, 3 and 6
      months postpartum. Cox regression analysis was performed to determine factors
      related to early introduction of complementary feeding. RESULTS: The median age
      at start of complementary feeding was 4.5 months (95% confidence interval [CI]:
      4.4-4.6 months). Mothers who perceived that most of their friends breast-fed
      (adjusted hazard ratio [HR], 0.70; 95%CI: 0.58-0.84) and those who returned to
      work when the infants were at least 6 months old were less likely to initiate
      complementary feeding early (adjusted HR, 0.73; 95%CI: 0.58-0.91), while infants
      who had been introduced to infant formula regularly before 6 months of age were
      at a higher risk of receiving complementary foods prematurely (adjusted HR, 1.81;
      95%CI: 1.42-2.31). CONCLUSIONS: Introducing complementary feeding before 6 months
      postpartum was widely practiced in Jiangyou. The appropriate age at which to
      introduce complementary foods and its benefits need to be emphasized in the
      future breast-feeding education strategies in Sichuan.

PMID- 24931400
TI  - What is your diagnosis? Urine sediment changes in a dog with hemorrhagic shock
      and disseminated intravascular coagulation after pyometra surgery.

PMID- 24931403
TI  - Morphological approach to assess the involvement of astrocytes in prion
      propagation.
AB  - Transmissible Spongiform Encephalopathies (TSEs) are a group of neurodegenerative
      disorders affecting animals and humans and for which no effective treatment is
      available to date. Vacuolation, neuronal/neurite degeneration, deposition of
      pathological prion protein (PrPsc) and gliosis are changes typically found in
      brains from TSE affected individuals. However, the actual role of this last
      feature, microgliosis and astrocytosis, has not been precisely determined. The
      overall objective of this work is to assess the involvement of glial cells as
      components of the host protective system in prion propagation; specifically, to
      analyze the behavior of astroglial cells in prion progression. To achieve this
      aim, histopathological and immunohistochemical techniques were carried out on
      samples from cerebella using Scrapie as the prototype of natural TSEs as this
      made it possible to assess different stages of the disease; specifically, ages
      and genotypes from Scrapie-affected animals corresponding to different sources,
      by using optical, confocal and electron microscopy. The results provided in the
      present study demonstrate the indisputable involvement of astroglia in prion
      progression by showing specific changes of this glial population matching up to
      the evolution of the disease. Moreover, cerebellar lesions mainly associated to
      Purkinje cells that have not previously been reported in animal prion diseases in
      natural transmission are described here. The close relationship between PrPsc and
      GFAP hiperimmunoreactivity and Purkinje cells, alongside the evident thickening
      of their neurites at terminal stages demonstrated in this study, suggest that
      these neurons are the main target of this neurodegenerative disease. 

PMID- 24931404
TI  - Defining the post-operative morbidity index for distal pancreatectomy.
AB  - BACKGROUND: Accurate assessment of complications is critical in analysing
      surgical outcomes. The post-operative morbidity index (PMI), derived from the
      Modified Accordion Severity Grading System and American College of Surgeons
      National Surgical Quality Improvement Program (ACS-NSQIP), is a quantitative
      measure of post-operative morbidity. This study utilizes PMI to establish the
      complication burden for a distal pancreatectomy (DP). METHODS: From 2005-2011,
      nine centres contributed ACS-NSQIP complication data for 655 DPs. Each
      complication was assigned an Accordion severity weight ranging from 0.11 for
      grade 1 to 1.00 for grade 6 (death). The PMI is the sum of complication severity
      weights divided by the total number of patients. RESULTS: ACS-NSQIP complications
      occurred in 177 patients (27.0%). The non risk-adjusted PMI for DP is 0.087.
      Bleeding/Transfusion and Organ Space Infection were the most common
      complications. Frequency and burden differed across Accordion grades. While grade
      4-6 complications represented only 15.4% of complication occurrences, they
      accounted for 30.4% of the burden. Subgroup analysis demonstrates that the PMI
      did not vary based on laparoscopic versus open approach or the performance of a
      splenectomy. DISCUSSION: This study uses two validated systems to quantitatively
      establish the morbidity of a DP. The PMI allows estimation of both the frequency
      and severity of complications and thus provides a more comprehensive assessment
      of risk.

PMID- 24931401
TI  - Same task, different strategies: how brain networks can be influenced by memory
      strategy.
AB  - Previous functional neuroimaging studies demonstrated that different neural
      networks underlie different types of cognitive processing by engaging
      participants in particular tasks, such as verbal or spatial working memory (WM)
      tasks. However, we report here that even when a WM task is defined as verbal or
      spatial, different types of memory strategies may be used to complete it, with
      concomitant variations in brain activity. We developed a questionnaire to
      characterize the type of strategy used by individual members in a group of 28
      young healthy participants (18-25 years) during a spatial WM task. A cluster
      analysis was performed to differentiate groups. We acquired functional
      magnetoencephalography and structural diffusion tensor imaging measures to
      characterize the brain networks associated with the use of different strategies.
      We found two types of strategies were used during the spatial WM task, a
      visuospatial and a verbal strategy, and brain regions and time courses of
      activation differed between participants who used each. Task performance also
      varied by type of strategy used with verbal strategies showing an advantage. In
      addition, performance on neuropsychological tests (indices from Wechsler Adult
      Intelligence Scale-IV, Rey Complex Figure Test) correlated significantly with
      fractional anisotropy measures for the visuospatial strategy group in white
      matter tracts implicated in other WM and attention studies. We conclude that
      differences in memory strategy can have a pronounced effect on the locations and
      timing of brain activation and that these differences need further investigation
      as a possible confounding factor for studies using group averaging as a means for
      summarizing results.

PMID- 24931406
TI  - A critical component of meiotic drive in Neurospora is located near a chromosome
      rearrangement.
AB  - Neurospora fungi harbor a group of meiotic drive elements known as Spore killers
      (Sk). Spore killer-2 (Sk-2) and Spore killer-3 (Sk-3) are two Sk elements that
      map to a region of suppressed recombination. Although this recombination block is
      limited to crosses between Sk and Sk-sensitive (Sk(S)) strains, its existence has
      hindered Sk characterization. Here we report the circumvention of this obstacle
      by combining a classical genetic screen with next-generation sequencing
      technology and three-point crossing assays. This approach has allowed us to
      identify a novel locus called rfk-1, mutation of which disrupts spore killing by
      Sk-2. We have mapped rfk-1 to a 45-kb region near the right border of the Sk-2
      element, a location that also harbors an 11-kb insertion (Sk-2(INS1)) and part of
      a >220-kb inversion (Sk-2(INV1)). These are the first two chromosome
      rearrangements to be formally identified in a Neurospora Sk element, providing
      evidence that they are at least partially responsible for Sk-based recombination
      suppression. Additionally, the proximity of these chromosome rearrangements to
      rfk-1 (a critical component of the spore-killing mechanism) suggests that they
      have played a key role in the evolution of meiotic drive in Neurospora. 

PMID- 24931405
TI  - Testing models of the APC tumor suppressor/beta-catenin interaction reshapes our
      view of the destruction complex in Wnt signaling.
AB  - The Wnt pathway is a conserved signal transduction pathway that contributes to
      normal development and adult homeostasis, but is also misregulated in human
      diseases such as cancer. The tumor suppressor adenomatous polyposis coli (APC) is
      an essential negative regulator of Wnt signaling inactivated in >80% of
      colorectal cancers. APC participates in a multiprotein "destruction complex" that
      targets the proto-oncogene beta-catenin for ubiquitin-mediated proteolysis;
      however, the mechanistic role of APC in the destruction complex remains unknown.
      Several models of APC function have recently been proposed, many of which have
      emphasized the importance of phosphorylation of high-affinity beta-catenin
      binding sites [20-amino-acid repeats (20Rs)] on APC. Here we test these models by
      generating a Drosophila APC2 mutant lacking all beta-catenin-binding 20Rs and
      performing functional studies in human colon cancer cell lines and Drosophila
      embryos. Our results are inconsistent with current models, as we find that beta
      catenin binding to the 20Rs of APC is not required for destruction complex
      activity. In addition, we generate an APC2 mutant lacking all beta-catenin
      binding sites (including the 15Rs) and find that a direct beta-catenin/APC
      interaction is also not essential for beta-catenin destruction, although it
      increases destruction complex efficiency in certain developmental contexts.
      Overall, our findings support a model whereby beta-catenin-binding sites on APC
      do not provide a critical mechanistic function per se, but rather dock beta
      catenin in the destruction complex to increase the efficiency of beta-catenin
      destruction. Furthermore, in Drosophila embryos expressing some APC2 mutant
      transgenes we observe a separation of beta-catenin destruction and Wg/Wnt
      signaling outputs and suggest that cytoplasmic retention of beta-catenin likely
      accounts for this difference. 

PMID- 24931408
TI  - A simple regression-based method to map quantitative trait loci underlying
      function-valued phenotypes.
AB  - Most statistical methods for quantitative trait loci (QTL) mapping focus on a
      single phenotype. However, multiple phenotypes are commonly measured, and recent
      technological advances have greatly simplified the automated acquisition of
      numerous phenotypes, including function-valued phenotypes, such as growth
      measured over time. While methods exist for QTL mapping with function-valued
      phenotypes, they are generally computationally intensive and focus on single-QTL
      models. We propose two simple, fast methods that maintain high power and
      precision and are amenable to extensions with multiple-QTL models using a
      penalized likelihood approach. After identifying multiple QTL by these
      approaches, we can view the function-valued QTL effects to provide a deeper
      understanding of the underlying processes. Our methods have been implemented as a
      package for R, funqtl. 

PMID- 24931407
TI  - Operons are a conserved feature of nematode genomes.
AB  - The organization of genes into operons, clusters of genes that are co-transcribed
      to produce polycistronic pre-mRNAs, is a trait found in a wide range of
      eukaryotic groups, including multiple animal phyla. Operons are present in the
      class Chromadorea, one of the two main nematode classes, but their distribution
      in the other class, the Enoplea, is not known. We have surveyed the genomes of
      Trichinella spiralis, Trichuris muris, and Romanomermis culicivorax and
      identified the first putative operons in members of the Enoplea. Consistent with
      the mechanism of polycistronic RNA resolution in other nematodes, the mRNAs
      produced by genes downstream of the first gene in the T. spiralis and T. muris
      operons are trans-spliced to spliced leader RNAs, and we are able to detect
      polycistronic RNAs derived from these operons. Importantly, a putative
      intercistronic region from one of these potential enoplean operons confers
      polycistronic processing activity when expressed as part of a chimeric operon in
      Caenorhabditis elegans. We find that T. spiralis genes located in operons have an
      increased likelihood of having operonic C. elegans homologs. However, operon
      structure in terms of synteny and gene content is not tightly conserved between
      the two taxa, consistent with models of operon evolution. We have nevertheless
      identified putative operons conserved between Enoplea and Chromadorea. Our data
      suggest that operons and "spliced leader" (SL) trans-splicing predate the
      radiation of the nematode phylum, an inference which is supported by the
      phylogenetic profile of proteins known to be involved in nematode SL trans
      splicing. 

PMID- 24931411
TI  - Current status and future direction of cardiac resynchronization therapy for
      congenital heart disease and pediatric patients.

PMID- 24931409
TI  - Neuronal remodeling during metamorphosis is regulated by the alan shepard (shep)
      gene in Drosophila melanogaster.
AB  - Peptidergic neurons are a group of neuronal cells that synthesize and secrete
      peptides to regulate a variety of biological processes. To identify genes
      controlling the development and function of peptidergic neurons, we conducted a
      screen of 545 splice-trap lines and identified 28 loci that drove expression in
      peptidergic neurons when crossed to a GFP reporter transgene. Among these lines,
      an insertion in the alan shepard (shep) gene drove expression specifically in
      most peptidergic neurons. shep transcripts and SHEP proteins were detected
      primarily and broadly in the central nervous system (CNS) in embryos, and this
      expression continued into the adult stage. Loss of shep resulted in late pupal
      lethality, reduced adult life span, wing expansion defects, uncoordinated adult
      locomotor activities, rejection of males by virgin females, and reduced neuropil
      area and reduced levels of multiple presynaptic markers throughout the adult CNS.
      Examination of the bursicon neurons in shep mutant pharate adults revealed
      smaller somata and fewer axonal branches and boutons, and all of these cellular
      phenotypes were fully rescued by expression of the most abundant wild-type shep
      isoform. In contrast to shep mutant animals at the pharate adult stage, shep
      mutant larvae displayed normal bursicon neuron morphologies. Similarly, shep
      mutant adults were uncoordinated and weak, while shep mutant larvae displayed
      largely, although not entirely, normal locomotor behavior. Thus, shep played an
      important role in the metamorphic development of many neurons. 

PMID- 24931410
TI  - Nucleoporin FG domains facilitate mRNP remodeling at the cytoplasmic face of the
      nuclear pore complex.
AB  - Directional export of messenger RNA (mRNA) protein particles (mRNPs) through
      nuclear pore complexes (NPCs) requires multiple factors. In Saccharomyces
      cerevisiae, the NPC proteins Nup159 and Nup42 are asymmetrically localized to the
      cytoplasmic face and have distinct functional domains: a phenylalanine-glycine
      (FG) repeat domain that docks mRNP transport receptors and domains that bind the
      DEAD-box ATPase Dbp5 and its activating cofactor Gle1, respectively. We
      speculated that the Nup42 and Nup159 FG domains play a role in positioning mRNPs
      for the terminal mRNP-remodeling steps carried out by Dbp5. Here we find that
      deletion (Delta) of both the Nup42 and Nup159 FG domains results in a cold
      sensitive poly(A)+ mRNA export defect. The nup42DeltaFG nup159DeltaFG mutant also
      has synthetic lethal genetic interactions with dbp5 and gle1 mutants. RNA cross
      linking experiments further indicate that the nup42DeltaFG nup159DeltaFG mutant
      has a reduced capacity for mRNP remodeling during export. To further analyze the
      role of these FG domains, we replaced the Nup159 or Nup42 FG domains with FG
      domains from other Nups. These FG "swaps" demonstrate that only certain FG
      domains are functional at the NPC cytoplasmic face. Strikingly, fusing the Nup42
      FG domain to the carboxy-terminus of Gle1 bypasses the need for the endogenous
      Nup42 FG domain, highlighting the importance of proximal positioning for these
      factors. We conclude that the Nup42 and Nup159 FG domains target the mRNP to Gle1
      and Dbp5 for mRNP remodeling at the NPC. Moreover, these results provide key
      evidence that character and context play a direct role in FG domain function and
      mRNA export. 

PMID- 24931412
TI  - Perioperative plasma neutrophil gelatinase-associated lipocalin measurement in
      patients who undergo left ventricular assist device implantation surgery.
AB  - BACKGROUND: Perioperative complication of end-organ injury including acute kidney
      injury (AKI) is a frequent and severe problem for patients undergoing left
      ventricular assist device (LVAD) implantation. This study evaluated an emerging
      AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), in a
      LVAD implantation cohort. METHODS AND RESULTS: Of 31 LVAD implantation patients
      enrolled to this study, 17 (55%) patients were diagnosed as having AKI. Six AKI
      patients showed severe AKI requiring renal replacement therapy (RRT). Plasma NGAL
      values in the AKI-with-RRT group (n=6) were significantly higher than that in
      other patients, although the AKI-without-RRT (n=11) group showed a similar level
      of plasma NGAL to that of the non-AKI group (n=14). Multiple logistic regression
      analysis revealed that plasma NGAL measured at pre-operation and central venous
      pressure at pre-operation and 12 h after surgery independently discriminated
      against postoperative RRT requirement. In the AKI-with-RRT group, plasma NGAL
      decreased before termination of RRT in 4 patients who eventually showed renal
      recovery, although no decline of plasma NGAL was observed in 2 patients who
      showed no recovery of renal function. Removal of blood NGAL by continuous
      hemodiafiltration was shown to be 70-75% lower than that of creatinine.
      CONCLUSIONS: Measurement of perioperative plasma NGAL is useful for predicting
      severe AKI requiring RRT and renal recovery in patients who have had LVAD
      implantation surgery. Further investigation is necessary to confirm these
      findings because this study examined a low number of patients.

PMID- 24931413
TI  - Implementation of a low-cost laparoscopic skills curriculum in a third-world
      setting.
AB  - BACKGROUND: Training outside the operating room has become a mainstay of surgical
      education. Laparoscopic training often takes place in a simulation setting.
      Advanced laparoscopic procedures are now commonplace, even in third-world
      countries with minimal hospital resources. We sought to implement a low-cost
      laparoscopic skills curriculum in a general surgery residency program in East
      Africa. STUDY DESIGN: The laparoscopic skills curriculum created and validated at
      the University of Kentucky was presented to the 10 general surgery residents at
      Tenwek Hospital. The curriculum and all materials were purchased for
      approximately $50 (USD). The residents in Kenya had access to laparoscopic
      trainer boxes and personal laptops to perform the simulations. Residents were
      timed on their performance at the initiation of the project and after 3 weeks of
      practice. RESULTS: Residents were tested on 3 separate tasks (cannulation drill,
      peg board, and rope pass). At the initiation of the project, residents were
      unable to complete the 3 tasks chosen for timing without a critical error (i.e.,
      dropping a peg out of view). After 3 weeks of independent practice, residents
      were able to successfully complete the tasks, nearing the time limits established
      in the curriculum manual. Additional practice and testing sessions are scheduled
      for the remainder of the year. CONCLUSIONS: Implementation of a low-cost
      laparoscopic skills curriculum in a third-world setting is feasible. This
      approach offers much-needed exposure and opportunities for residents with
      extremely limited resources and promises to be a vital aspect of the growing
      surgical residency training in third-world settings.

PMID- 24931415
TI  - Do medical students in the operating room affect patient care? An analysis of one
      institution's experience over the past five years.
AB  - BACKGROUND: Medical students are active learners in operating rooms during
      medical school. This observational study seeks to investigate the effect of
      medical students on operative time and complications. METHODS: Data from the
      American College of Surgeons National Surgical Quality Improvement Program was
      linked to operative records for nonemergent, inpatient general surgery cases at
      our institution from 1 January 2009 to 1 January 2013. Cases were grouped into 13
      distinct procedure groups. Hospital records provided information on the presence
      of medical students. Demographics, comorbidities, intraoperative variables, and
      postoperative complications were analyzed. RESULTS: Overall, 2481 cases were
      included. Controlling for wound class, procedure group, and surgeon, medical
      students were associated with an additional 14 minutes of operative time. No
      association between medical students and postoperative complications was
      observed. CONCLUSIONS: The educational benefits gained by the presence of medical
      students do not appear to jeopardize the quality of patient care.

PMID- 24931414
TI  - Surgeon as educator: bedside ultrasound in hypertrophic pyloric stenosis.
AB  - OBJECTIVE: Our institution has demonstrated the diagnostic accuracy of surgeon
      performed ultrasound (US) in the diagnosis of hypertrophic pyloric stenosis
      (HPS). Moreover, we have also shown this modality to be accurate and reproducible
      through surgeon-to-surgeon instruction. The purpose of this study was to
      determine whether a surgical resident with experience in diagnosing HPS can teach
      pediatric emergency medicine (PEM) fellows, with little experience in sonography,
      to accurately measure the pyloric channel with bedside US. METHODS: A surgical
      resident with experience in diagnosing HPS with US-proctored 4 emergency medicine
      fellows for 5 bedside US examinations each. A PEM fellow, who was blinded to the
      results from the radiology department US, then performed bedside US and measured
      the pyloric channel in patients presenting to the emergency department with HPS.
      Results between the radiology department and the fellows were compared using the
      Student t test. RESULTS: In total, 18 USs were performed on 17 patients. There
      were no false-negative or false-positive results. There was no statistical
      difference between the radiology department and fellow measurement when
      evaluating muscle width (p = 0.21, mean deviation = 0.2 mm) or channel length (p
      = 0.47, mean deviation = 0.6 mm). CONCLUSION: Bedside-performed US technique for
      measuring the pylorus length and width in patients with HPS is reproducible and
      accurate when taught to PEM providers. The learning curve for this technique is
      short.

PMID- 24931416
TI  - Do residents receive the same OR guidance as surgeons report? Difference between
      residents' and surgeons' perceptions of OR guidance.
AB  - PURPOSE: Operating room (OR) guidance is important for surgical residents'
      performance and, ultimately, for the development of independence and autonomy.
      This study explores the differences in surgical residents' and attending
      surgeons' perceptions of OR guidance in prerecorded surgical cases. METHODS: A
      total of 9 attending surgeons and 8 surgical residents observed 8 prerecorded
      surgical cases and were asked to identify both the presence and the type of
      attending surgeons' OR guidance. Each recorded case was observed by 2 attending
      surgeons and 1 resident. A previously developed taxonomy for types of OR guidance
      was applied to analyze the data to explore the difference. Agreement by both
      attending surgeons on the presence and the type of OR guidance served as the
      concordant guidance behaviors to which the responses of the residents were
      compared. RESULTS: Overall, 116 OR guidance events were identified. Attending
      surgeons agreed on the presence of guidance in 80 of 116 (69.8%) events and
      consistently identified the type of OR guidance in 91.4% (73/80, Cohen kappa =
      0.874) of them. However, surgical residents only agreed with attending surgeons
      on the presence of guidance in 61.25% (49/80) of the events. In addition, there
      was significant disagreement (Cohen kappa = 0.319) between surgical residents and
      attending surgeons in the type of OR guidance; the residents only identified
      54.8% (40/73) of concordant guidance behaviors in the same guidance category as
      both the surgeons. Among the types of OR guidance, residents and attending
      surgeons were most likely to agree on the teaching guidance (66.67%) and least
      likely to agree on the assisting guidance (36.84%). CONCLUSIONS: Surgical
      residents and attending surgeons have different perceptions of both the presence
      and the type of OR guidance. This difference in perception of OR guidance has
      important implications for the efficiency of training surgical residents in the
      OR, and, ultimately on residents' development of independence and autonomy.

PMID- 24931418
TI  - Molecular modeling study of the recognition mechanism and enantioseparation of 4
      hydroxypropranolol by capillary electrophoresis using carboxymethyl-beta
      cyclodextrin as the chiral selector.
AB  - The purpose of this paper was to study at the molecular level the
      enantioseparation mechanism of 4-hydroxypropranolol (4-OH-Prop) with
      carboxymethyl-beta-cyclodextrin (CM-beta-CD) using a sequential methodology which
      included molecular dynamics simulations (MD), and Parametric Model 3 (PM3)
      semiempirical and density functional theory (DFT) calculations. A systematic
      structural analysis indicated that hydrogen bonds formed between the host and
      guests play a major role in the complex stabilization. The inclusion complex (+)
      (R)-4-OH-Prop/CM-beta-CD showed three strong intermolecular hydrogen bonds.
      Moreover, the guest inclusion process made from a wider CD rim presented lower
      energies (interaction and Gibbs free energy) in comparison to the inclusion made
      by a narrower CD rim in both gas and aqueous phases. This difference in energies
      of drug/CM-beta-CD inclusion complexes is probably a measure of chiral
      discrimination, which results in the separation of the enantiomers and the
      distinct separation factors as observed in previous experimental findings.
      Comparing the experimental results of the separation of 4-OH-Prop enantiomers by
      capillary electrophoresis (CE), the proposed theoretical model demonstrated good
      capability to predict chiral separation of 4-OH-Prop enantiomers as well as the
      qualitative estimative of chiral recognition mechanism. 

PMID- 24931417
TI  - CCL2 release by airway smooth muscle is increased in asthma and promotes
      fibrocyte migration.
AB  - BACKGROUND: Asthma is characterized by variable airflow obstruction, airway
      inflammation, airway hyper-responsiveness and airway remodelling. Airway smooth
      muscle (ASM) hyperplasia is a feature of airway remodelling and contributes to
      bronchial wall thickening. We sought to investigate the expression levels of
      chemokines in primary cultures of ASM cells from asthmatics vs healthy controls
      and to assess whether differentially expressed chemokines (i) promote fibrocyte
      (FC) migration towards ASM and (ii) are increased in blood from subjects with
      asthma and in sputum samples from those asthmatics with bronchial wall
      thickening. METHODS: Chemokine concentrations released by primary ASM were
      measured by MesoScale Discovery platform. The chemokine most highly expressed by
      ASM from asthmatics compared with healthy controls was confirmed by ELISA, and
      expression of its cognate chemokine receptor by FCs was examined by
      immunofluorescence and flow cytometry. The role of this chemokine in FC migration
      towards ASM was investigated by chemotaxis assays. RESULTS: Chemokine (C-C motif)
      ligand 2 (CCL2) levels were increased in primary ASM supernatants from asthmatics
      compared with healthy controls. CCR2 was expressed on FCs. Fibrocytes migrated
      towards recombinant CCL2 and ASM supernatants. These effects were inhibited by
      CCL2 neutralization. CCL2 levels were increased in blood from asthmatics compared
      with healthy controls, and sputum CCL2 was increased in asthmatics with bronchial
      wall thickening. CONCLUSIONS: Airway smooth muscle-derived CCL2 mediates FC
      migration and potentially contributes to the development of ASM hyperplasia in
      asthma.

PMID- 24931419
TI  - Statistical considerations associated with a comprehensive regulatory framework
      to address the unmet need for new antibacterial therapies.
AB  - At present, there are situations in antibiotic drug development where the low
      number of enrollable patients with key problem pathogens makes it impossible to
      conduct fully powered non-inferiority trials in the traditional way. Recent
      regulatory changes have begun to address this situation. In parallel, statistical
      issues regarding the application of alternative techniques, balancing the unmet
      need with the level of certainty in the approval process, and the use of
      additional sources of data are critical areas to increase development
      feasibility. Although such approaches increase uncertainty compared with a
      traditional development program, this will be necessary to allow new agents to be
      made available. Identification of these risks and explicit discussion around
      requirements in these areas should help clarify the situation, and hence, the
      feasibility of developing drugs to treat the most concerning pathogens before the
      unmet need becomes even more acute than at present.

PMID- 24931420
TI  - A novel F8 -/- rat as a translational model of human hemophilia A.
AB  - BACKGROUND: In preclinical hemophilia research, an animal model that reflects
      both the phenotype and the pathology of the disease is needed. OBJECTIVES: Here,
      we describe the generation and characterization of a novel genetically engineered
      F8(-/-) rat model. METHODS: The rats were produced on a Sprague Dawley background
      with the zinc finger nuclease technique. A founder with a 13-bp deletion in exon
      16 causing a premature translational stop in the C-terminal part of the A3 domain
      of factor VIII was selected, and a breeding colony was established. RESULTS:
      Seventy per cent of the homozygous rats had clinically manifest spontaneous
      hemorrhagic episodes that needed treatment. The F8(-/-) rats had no detectable
      FVIII activity, and had a significantly prolonged activated partial
      thromboplastin time (APTT) and clot formation time as compared with wild-type
      (WT)/WT rats. In vitro spiking of rat plasma with human recombinant FVIII
      resulted in dose-dependent normalization of the APTT. CONCLUSION: On the basis of
      the targeted deletion in F8, and the distinct physical and analytic
      characteristics of the rat, we conclude that an FVIII-deficient rat strain has
      been generated that has the potential to contribute greatly to translational
      research.

PMID- 24931421
TI  - Tacrolimus dosage requirements in lung transplant recipients receiving antifungal
      prophylaxis with voriconazole followed by itraconazole: a preliminary prospective
      study.
AB  - BACKGROUND: Concomitant administration of the triazole antifungals, voriconazole
      or itraconazole, with tacrolimus can result in significant drug interaction in
      the transplant recipient. Limited published information exists regarding
      tacrolimus dosing when transitioning from voriconazole to itraconazole. The
      objective of this study was to evaluate the extent of the drug interaction with
      antifungal prophylaxis using voriconazole followed by a change to itraconazole in
      lung transplant recipients receiving tacrolimus. METHODS: This prospective study
      included lung transplant recipients receiving antifungal prophylaxis with
      voriconazole followed by a switch to itraconazole. Patients were followed from
      the time of transplant until two months after converting to itraconazole. All
      patients received standard immunosuppression with tacrolimus, mycophenolate
      mofetil, and a corticosteroid. Tacrolimus dose normalized concentrations using
      concentration/dose ratio were compared while receiving voriconazole versus
      itraconazole. RESULTS: Twenty lung transplant recipients were included in the
      final analysis. No difference was found with the tacrolimus dose normalized
      concentrations on voriconazole 254 +/- 28 (ng/mL)/(mg/kg) compared with
      itraconazole 234 +/- 34 (ng/mL)/(mg/kg), p = 0.65. CONCLUSION: Tacrolimus dosage
      adjustments were not necessary when converting from voriconazole to itraconazole.
      Validation in a larger population is needed to confirm these findings.

PMID- 24931422
TI  - Metal ion-mediated assembly of DNA nanostructures for cascade fluorescence
      resonance energy transfer-based fingerprint analysis.
AB  - Contamination of heavy metal ions in an aquatic environment poses a serious
      threat to human health. More seriously, heavy metal ions are usually present in
      the environment in a mixture, and the synergetic toxicity of multiple heavy metal
      ions is revealed (Aragay et al. Chem. Rev. 2011, 111, 3433; Chu et al. Aquat.
      Toxicol. 2002, 61, 53). Unfortunately, most of the existing methods based on DNA
      sequences are focusing on the detection of one type of metal ions. Simple and
      multiplexed detection of multiple metal ions has been poorly investigated and
      remains challenging. Here, we re-engineered the DNA sequences for Pb(2+), Hg(2+),
      and Ag(+), through which the binding of multiple metal ions initiated the self
      assembly of these DNA sequences. On the basis of our rationally designed
      multicolor fluorescent labeling of the DNA sequences, cascade fluorescence
      resonance energy transfer (FRET) occurred. As a result, a fingerprint fluorescent
      spectrum was produced to indicate the presence of a single type of metal ions or
      multiple metal ions. The major advantages of our cascade FRET fingerprint
      technology include the following: (1) the "mix and read" detection mode in
      homogeneous solution is simple without the need of complicated instruments; (2)
      only single excitation is required to provide the cascade FRET fingerprint
      spectrum; (3) multiplexed detection capability can be realized intuitively and
      sensitively.

PMID- 24931424
TI  - Sonochemical synthesis of Pr-doped ZnO nanoparticles for sonocatalytic
      degradation of Acid Red 17.
AB  - Undoped and Pr-doped ZnO nanoparticles were prepared using a simple sonochemical
      method, and their sonocatalytic activity was investigated toward degradation of
      Acid Red 17 (AR17) under ultrasonic (US) irradiation. Synthesized nanoparticles
      were characterized by X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) techniques. The
      extent of sonocatalytic degradation was higher compared with sonolysis alone. The
      decolorization efficiency of sonolysis alone, sonocatalysis with undoped ZnO and
      5% Pr-doped ZnO was 24%, 46% and 100% within reaction time of 70min,
      respectively. Sonocatalytic degradation of AR17 increased with increasing the
      amount of dopant and catalyst dosage and decreasing initial dye concentration.
      Natural pH was favored the sonocatalytic degradation of AR17. With the addition
      of chloride, carbonate and sulfate as radical scavengers, the decolorization
      efficiency was decreased from 100% to 65%, 71% and 89% at the reaction time of
      70min, respectively, indicating that the controlling mechanism of sonochemical
      degradation of AR17 is the free radicals (not pyrolysis). The addition of
      peroxydisulfate and hydrogen peroxide as enhancer improved the degradation
      efficiency from 79% to 85% and 93% at the reaction time of 50min, respectively.
      The result showed good reusability of the synthesized sonocatalyst. 

PMID- 24931423
TI  - Differential activation of placental unfolded protein response pathways implies
      heterogeneity in causation of early- and late-onset pre-eclampsia.
AB  - Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is
      commonly divided into early-onset (<34 weeks) and late-onset (>=34 weeks) forms.
      Recently, the distinction between 'placental' and 'maternal' causation has been
      proposed, with 'placental' cases being more frequently associated with early
      onset and intrauterine growth restriction. To test whether molecular placental
      pathology varies according to clinical presentation, we investigated stress
      signalling pathways, including unfolded protein response (UPR) pathways, MAPK
      stress pathways, heat-shock proteins and AMPKalpha in placentae delivered by
      caesarean section for clinical indications at different gestational ages.
      Controls included second-trimester, pre-term and normal-term placentae. BeWo
      cells were used to investigate how these pathways react to different severities
      of hypoxia-reoxygenation (H/R) and pro-inflammatory cytokines. Activation of
      placental UPR and stress-response pathways, including P-IRE1alpha, ATF6, XBP-1,
      GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both
      late-onset PE and normotensive controls (NTCs), with a clear inflection around 34
      weeks. Placentae from >= 34 weeks PE and NTC were indistinguishable. Levels of
      UPR signalling were similar between second-trimester and term controls, but were
      significantly higher in pre-term 'controls' delivered vaginally for
      chorioamnionitis and other conditions. Severe H/R (1/20% O2 ) induced equivalent
      activation of UPR pathways, including P-eIF2alpha, ATF6, P-IRE1alpha, GRP78 and
      GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNFalpha and IL
      1beta induced only mild activation of P-eIF2alpha and GRP78. AKT, a central
      regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and
      severe H/R-treated cells, but not in other conditions. These findings provide the
      first molecular evidence that placental stress may contribute to the
      pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the
      case in the late-onset form of the syndrome.

PMID- 24931425
TI  - Rapid and efficient one-pot synthesis of spiro[indoline-3,4'-pyrano[2, 3
      c]pyrazole] derivatives catalyzed by l-proline under ultrasound irradiation.
AB  - A rapid and efficient ultrasound-promoted one-pot synthesis of spiro[indoline
      3,4'-pyrano[2,3-c]pyrazole] derivatives is described here. The reaction of
      substituted phenylhydrazine and dialkyl acetylenedicarboxylate with substituted
      isatin and malononitrile is catalyzed by l-proline to give good-to-excellent
      yields in water/ethanol (v/v, 1:1) at room temperature. 

PMID- 24931426
TI  - Bromate oxidized from bromide during sonolytic ozonation.
AB  - Sonolytic ozonation (US/O3) is an effective way to degrade many pollutants in
      drinking water as the elevated mass transfer rate of ozone gas and the enhanced
      forming of hydroxyl radicals (OH). This work investigated the formation of
      bromate (BrO3(-)) from bromide (Br(-)) in sonolytic ozonation. At neutral pH, the
      bromate conversion rate ([BrO3(-)]/[Br(-)]0) was increased to 60% by ultrasound
      at continuous ozone flow (0-0.2Lmin(-1)), much higher than that without
      ultrasound or without bubbling. This indicates that the promoting effect of
      sonolysis on BrO3(-) formation is mainly due to the sonolytic decomposition of
      ozone and the enhancement of gas-liquid transfer. The [BrO3(-)]/[Br(-)]0 was
      increased with increasing pH. In addition, the reduction of HOBr/OBr(-) with
      ultrasound demonstrates that bromate may be inhibited as the bromide was formed
      with the H2O2 generation under ultrasound. This suggests the competition between
      bromate and bromide during the US/O3 led to the inhibition of bromate formation
      at high ozone flow. Therefore, our result reveals that the bromate formation
      under ultrasound is improved remarkably in US/O3 in quick treatment with proper
      ozone flow (<0.2Lmin(-1)). 

PMID- 24931427
TI  - Maturation of membrane properties of neurons in the rat deep cerebellar nuclei.
AB  - Patch clamp recordings of neurons in the adult rat deep cerebellar nuclei have
      been limited by the availability of viable brain slices. Using a new slicing
      technique, this study was designed to explore the maturation of membrane
      properties of neurons in the deep cerebellar nuclei (DCN)-an area involved in rat
      eyeblink conditioning. Compared to whole-cell current-clamp recordings in DCN in
      rat pups at postnatal day 16 (P16) to P21, recordings from weanling rats at P22
      P40 revealed a number of significant changes including an increase in the
      amplitude of the afterhyperpolarization (AHP)-an index of membrane excitability
      which has been shown to be important for eyeblink conditioning-a prolonged
      interval between the first and second evoked action potential, and an increase in
      AHP amplitude for hyperpolarization-induced rebound spikes. This is the first
      report of developmental changes in membrane properties of DCN which may
      contribute to the ontogeny of eyeblink conditioning in the rat.

PMID- 24931428
TI  - Chronic aluminum intoxication in rat induced both serotonin changes in the dorsal
      raphe nucleus and alteration of glycoprotein secretion in the subcommissural
      organ: Immunohistochemical study.
AB  - Aluminum (Al) causes multiple impairments in several body systems including the
      central nervous system. In fact, Al exposure has been mostly associated with
      neurological dysfunctions that occur in some brain diseases. The effect of Al
      neurotoxicity on the dopaminergic system is well documented, but this effect on
      the serotoninergic system is poorly studied. The aim of this work is to evaluate
      the effect of chronic Al intoxication (0.3% of aluminum chloride exposure from
      the intra-uterine age until 4 months of adult age) on dorsal raphe nucleus (DRN)
      which is the main source of serotonin, and also on the glycoprotein secretion of
      subcomissural organ (SCO), receiving important serotoninergic innervation. This
      will be executed using immunohistochemistry procedure, with both the anti
      serotonin and the anti Reissner's fiber antibodies in the rat. Our results showed
      a significant increase of serotonin immunoreactivity in the DRN, accompanied by a
      noticeable decrease of RF immunoreactivity in the SCO ependymocytes. This study
      provides further evidence confirming the toxic effect of Al exposure on serotonin
      neurotransmission in the brain likely through increased synthesis or decreased
      release. Al exposure was also shown to decrease RF glycoprotein which is involved
      in the detoxification of cerebrospinal fluid. 

PMID- 24931429
TI  - Measurement of rivaroxaban and apixaban in serum samples of patients.
AB  - BACKGROUND: The determination of rivaroxaban and apixaban from serum samples of
      patients may be beneficial in specific clinical situations when additional blood
      sampling for plasma and thus the determination of factor Xa activity is not
      feasible or results are not plausible. MATERIALS AND METHODS: The primary aim of
      this study was to compare the concentrations of rivaroxaban and apixaban in serum
      with those measured in plasma. Secondary aims were the performance of three
      different chromogenic methods and concentrations in patients on treatment with
      rivaroxaban 10 mg od (n = 124) or 20 mg od (n = 94) or apixaban 5 mg bid (n = 52)
      measured at different time. RESULTS: Concentrations of rivaroxaban and apixaban
      in serum were about 20-25% higher compared with plasma samples with a high
      correlation (r = 0.79775-0.94662) using all assays (all P < 0.0001). The
      intraclass correlation coefficients were about 0.90 for rivaroxaban and 0.55 for
      apixaban. Mean rivaroxaban concentrations were higher at 2 and 3 h compared with
      1 and 12 h after administration measured from plasma and serum samples (all P
      values < 0.05) and were not different between 1 vs. 12 h (plasma and serum).
      CONCLUSIONS: The results indicate that rivaroxaban and apixaban concentrations
      can be determined specifically from serum samples.

PMID- 24931430
TI  - Comorbidities and causes of death in the management of localized T1a kidney
      cancer.
AB  - OBJECTIVE: The objectives of the present study were analyze specific
      comorbidities associated with survival and actual causes of death for patients
      with small renal masses, and to suggest a simplified measure associated with
      decreased overall survival specific to this population. METHODS: The
      Surveillance, Epidemiology and End Results-Medicare database (1995-2007) was
      queried to identify patients with localized T1a kidney cancer undergoing partial
      nephrectomy, radical nephrectomy or deferring therapy. We explored independent
      associations of specific comorbidities with causes of death, and developed a
      simplified cardiovascular index. Cox proportional hazards, and Fine and Gray
      competing risks regression were used. RESULTS: Of 7177 Medicare beneficiaries in
      the study population, 754 (10.5%) deferred therapy, 1849 (25.8%) underwent
      partial nephrectomy and 4574 (63.7%) underwent radical nephrectomy with none of
      the selected comorbidities identified in 3682 (51.3%) patients. Congestive heart
      failure, chronic kidney disease, peripheral vascular disease, chronic obstructive
      pulmonary disease, diabetes and cerebrovascular disease were associated with
      decreased overall survival. The cardiovascular index provided good survival risk
      stratification, and reclassified 1427 (41%) patients with a score >=1 on the
      Charlson Comorbidity Index to a 0 on the cardiovascular index with minimal
      concession of 5-year survival. CONCLUSIONS: Congestive heart failure, chronic
      kidney disease, peripheral vascular disease, chronic obstructive pulmonary
      disease, diabetes and cerebrovascular disease were associated with decreased
      overall survival among Medicare beneficiaries with small renal masses. The
      cardiovascular index could serve as a clinically useful prognostic aid when
      advising older patients that are borderline candidates for surgery or active
      surveillance.

PMID- 24931432
TI  - Associations between physical activity, sedentary time, sleep duration and
      daytime sleepiness in US adults.
AB  - OBJECTIVE: To examine the associations between objectively measured physical
      activity (PA) or sedentary behavior and self-reported sleep duration or daytime
      sleepiness in a nationally representative sample of healthy US adults (N=2128).
      METHODS: We report analyses of four aspects of sedentary behavior and PA derived
      from accelerometry data (minutes of sedentary time, activity counts/minute,
      Minutes of Moderate and Vigorous PA [MVPA], and MVPA in 10-minute bouts) versus
      self-report of sleep duration and frequency of daytime sleepiness from the 2005
      2006 National Health and Nutrition Examination Survey. RESULTS: Age and sex
      dependence of associations between PA and sleep were observed. Aspects of PA were
      significantly lower in adults reporting more frequent daytime sleepiness in
      younger (20-39) and older (>= 60) age groups, but not in middle-aged (40-59),
      respondents. In younger respondents, PA increased with sleep duration, but in
      middle aged and older respondents PA was either unrelated to sleep duration or
      lower in those reporting >= 8 h of sleep. Objectively measured sedentary time
      showed limited evidence of associations with sleep duration. CONCLUSIONS: Further
      research delineating the relationships between sleep and PA is important because
      both activities have been implicated in diverse health outcomes as well as in the
      etiology of obesity.

PMID- 24931431
TI  - Juvenile hormone regulates Aedes aegypti Kruppel homolog 1 through a conserved E
      box motif.
AB  - Juvenile hormone (JH) plays important roles in regulation of many physiological
      processes including development, reproduction and metabolism in insects. However,
      the molecular mechanisms of JH signaling pathway are not completely understood.
      To elucidate the molecular mechanisms of JH regulation of Kruppel homolog 1 gene
      (Kr-h1) in Aedes aegypti, we employed JH-sensitive Aag-2 cells developed from the
      embryos of this insect. In Aag-2 cells, AaKr-h1 gene is induced by nanomolar
      concentration of JH III, its expression peaked at 1.5 h after treatment with JH
      III. RNAi studies showed that JH induction of this gene requires the presence of
      Ae. aegypti methoprene-tolerant (AaMet). A conserved 13 nucleotide JH response
      element (JHRE, TGCCTCCACGTGC) containing canonical E box motif (underlined)
      identified in the promoter of AaKr-h1 is required for JH induction of this gene.
      Critical nucleotides in the JHRE required for JH action were identified by
      employing mutagenesis and reporter assays. Reporter assays also showed that basic
      helix loop helix (bHLH) domain of AaMet is required for JH induction of AaKr-h1.
      5' rapid amplification of cDNA ends method identified two isoforms of AaKr-h1,
      AaKr-h1alpha and AaKr-h1beta, the expression of both isoforms is induced by JH
      III, but AaKr-h1alpha is the predominant isoform in both Aag-2 cells and Ae.
      aegypti larvae. 

PMID- 24931433
TI  - Dog ownership and physical activity in later life: a cross-sectional
      observational study.
AB  - OBJECTIVE: To examine whether dog ownership amongst community dwelling older
      adults (>= 65 years) is associated with objectively measured physical activity
      (PA). METHODS: We used data from the Physical Activity Cohort Scotland (PACS)
      which consists of 547 people aged 65 and over, resident in the community in
      Tayside, Scotland. The data was collected in 2009-2011. We assessed whether dog
      ownership is associated with objectively measured physical activity
      (accelerometry counts). RESULTS: The physical activity (PA) counts of 547 older
      people (mean age 79 (standard deviation (SD) 8 years, 54% female) were analysed.
      Linear mixed models showed that dog ownership was positively related to higher PA
      levels. This positive relationship remained after controlling for a large number
      of individual and contextual variables, including attitude towards exercise,
      physical activity intention and history of physical activity. Dog owners were
      found to be 12% more active (21,875 counts, 95% Confidence Interval (CI): 2810 to
      40,939, p<0.05) than non-dog owners. CONCLUSION: Dog ownership is associated with
      physical activity in later life. Interventions to increase activity amongst older
      people might usefully attempt to replicate elements of the dog ownership
      experience.

PMID- 24931434
TI  - Technical desiderata for the integration of genomic data with clinical decision
      support.
AB  - The ease with which whole genome sequence (WGS) information can be obtained is
      rapidly approaching the point where it can become useful for routine clinical
      care. However, significant barriers will inhibit widespread adoption unless
      clinicians are able to effectively integrate this information into patient care
      and decision-making. Electronic health records (EHR) and clinical decision
      support (CDS) systems may play a critical role in this integration. A previously
      published technical desiderata focused primarily on the integration of genomic
      data into the EHR. This manuscript extends the previous desiderata by
      specifically addressing needs related to the integration of genomic information
      with CDS. The objective of this study is to develop and validate a guiding set of
      technical desiderata for supporting the clinical use of WGS through CDS. A panel
      of domain experts in genomics and CDS developed a proposed set of seven
      additional requirements. These desiderata were reviewed by 63 experts in genomics
      and CDS through an online survey and refined based on the experts' comments.
      These additional desiderata provide important guiding principles for the
      technical development of CDS capabilities for the clinical use of WGS
      information. 

PMID- 24931435
TI  - Source misattributions and false recognition errors: examining the role of
      perceptual resemblance and imagery generation processes.
AB  - In three experiments, we examine the extent to which participants' memory errors
      are affected by the perceptual features of an encoding series and imagery
      generation processes. Perceptual features were examined by manipulating the
      features associated with individual items as well as the relationships among
      items. An encoding instruction manipulation was included to examine the effects
      of explicit requests to generate images. In all three experiments, participants
      falsely claimed to have seen pictures of items presented as words, committing
      picture misattribution errors. These misattribution errors were exaggerated when
      the perceptual resemblance between pictures and images was relatively high
      (Experiment 1) and when explicit requests to generate images were omitted from
      encoding instructions (Experiments 1 and 2). When perceptual cues made the
      thematic relationships among items salient, the level and pattern of
      misattribution errors were also affected (Experiments 2 and 3). Results address
      alternative views about the nature of internal representations resulting in
      misattribution errors and refute the idea that these errors reflect only
      participants' general impressions or beliefs about what was seen. 

PMID- 24931436
TI  - Longitudinal magnetic resonance imaging of pseudotumors following metal-on-metal
      total hip arthroplasty.
AB  - The purpose of the study was to determine the natural history of pseudotumors
      following metal-on-metal total hip arthroplasty (THA) using magnetic resonance
      imaging (MRI). Initial MRI was conducted at a mean of 36months postoperatively.
      Follow-up MRI was performed at a mean of 20months after the detection of 24
      asymptomatic pseudotumors. Pseudotumor size was determined on MRI. The mean
      pseudotumor size changed from 729mm(2) to 877mm(2). Pseudotumors increased in
      size in eight and decreased in six. Ten hips showed no changes. The bigger the
      pseudotumor size, the more likely the size would increase. In conclusion,
      pseudotumors frequently change in size. A single MRI study in the clinical
      decision-making process should be avoided and a longitudinal study should be
      performed.

PMID- 24931437
TI  - Computational analysis of enhanced magnetic bioseparation in microfluidic systems
      with flow-invasive magnetic elements.
AB  - A microfluidic design is proposed for realizing greatly enhanced separation of
      magnetically-labeled bioparticles using integrated soft-magnetic elements. The
      elements are fixed and intersect the carrier fluid (flow-invasive) with their
      length transverse to the flow. They are magnetized using a bias field to produce
      a particle capture force. Multiple stair-step elements are used to provide
      efficient capture throughout the entire flow channel. This is in contrast to
      conventional systems wherein the elements are integrated into the walls of the
      channel, which restricts efficient capture to limited regions of the channel due
      to the short range nature of the magnetic force. This severely limits the channel
      size and hence throughput. Flow-invasive elements overcome this limitation and
      enable microfluidic bioseparation systems with superior scalability. This
      enhanced functionality is quantified for the first time using a computational
      model that accounts for the dominant mechanisms of particle transport including
      fully-coupled particle-fluid momentum transfer. 

PMID- 24931438
TI  - B-cell-activating factor code and human cytomegalovirus infection in renal
      transplant recipients.
AB  - The objective of the present study was to explore the correlation between the
      BAFF signal and HCMV-TLR activation in RTx recipients complicated by HCMV.
      Peripheral blood (anticoagulated by EDTA-Na2 ) and urine of 113 RTx recipients
      were collected; healthy volunteers were controlled. Urine HCMV-DNA was detected
      by real-time PCR. Recipients were classified into a positive group (>10,000
      copies/mL urine) and a negative group (<10,000 copies/mL urine). ELISA results
      showed that sBAFF, sera anti-HCMV pp65 immunoglobulin (Ig)G antibody, and total
      IgG all significantly increased in recipients with positive HCMV-DNA (>10,000
      copies/mL urine) (P < 0.05) compared with negative recipients (<10,000 copies/mL
      urine). In the positive group, HCMV-DNA copies and total IgG positively
      correlated with sBAFF (r = 0.988 and 0.625, respectively) (P < 0.05). Luminex
      assay results suggested that the incidence of anti-HLA I and II and MICA antibody
      obviously increased in positive recipients. The expression level of BAFF and BAFF
      R increased in positive recipients. A total of 88 particular genes-involved in
      TLR signaling pathways, NF-kappaB signaling pathways, and cytokine-cytokine
      receptor signaling pathways-were detected in real-time PCR chip assay. A total of
      46 genes were differentially expressed greater than two-fold, and the expression
      characteristic of BAFF-R was concordant with FACS results. Our findings are that
      activation of HCMV would induce or enhance the activation of BAFF code in RTx
      recipients, which may independently or cooperatively participate in renal
      allograft injury and decrease the long-term outcome of renal allografts.

PMID- 24931440
TI  - Open Source Patient-Controlled Analgesic Pump Requirements Documentation.
AB  - The dynamic nature of the medical domain is driving a need for continuous
      innovation and improvement in techniques for developing and assuring medical
      devices. Unfortunately, research in academia and communication between academics,
      industrial engineers, and regulatory authorities is hampered by the lack of
      realistic non-proprietary development artifacts for medical devices. In this
      paper, we give an overview of a detailed requirements document for a Patient
      Controlled Analgesic (PCA) pump developed under the US NSF's Food and Drug
      Administration (FDA) Scholar-in-Residence (SIR) program. This 60+ page document
      follows the methodology outlined in the US Federal Aviation Administrations (FAA)
      Requirements Engineering Management Handbook (REMH) and includes a domain
      overview, use cases, statements of safety & security requirements, and formal top
      level system architectural description. Based on previous experience with release
      of a requirements document for a cardiac pacemaker that spawned a number of
      research and pedagogical activities, we believe that the described PCA
      requirements document can be an important research enabler within the formal
      methods and software engineering communities.

PMID- 24931441
TI  - Variant Influenza Associated with Live Animal Markets, Minnesota.
AB  - Variant influenza viruses are swine-origin influenza A viruses that cause illness
      in humans. Surveillance for variant influenza A viruses, including
      characterization of exposure settings, is important because of the potential
      emergence of novel influenza viruses with pandemic potential. In Minnesota, we
      have documented variant influenza A virus infections associated with swine
      exposure at live animal markets. 

PMID- 24931439
TI  - Recent advances using zebrafish animal models for muscle disease drug discovery.
AB  - INTRODUCTION: Animal models have enabled great progress in the discovery and
      understanding of pharmacological approaches for treating muscle diseases like
      Duchenne muscular dystrophy. AREAS COVERED: With this article, the author
      provides the reader with a description of the zebrafish animal model, which has
      been employed to identify and study pharmacological approaches to muscle disease.
      In particular, the author focuses on how both large-scale chemical screens and
      targeted drug treatment studies have established zebrafish as an important model
      for muscle disease drug discovery. EXPERT OPINION: There are a number of
      opportunities arising for the use of zebrafish models for further developing
      pharmacological approaches to muscle diseases, including studying drug
      combination therapies and utilizing genome editing to engineer zebrafish muscle
      disease models. It is the author's particular belief that the availability of a
      wide range of zebrafish transgenic strains for labeling immune cell types,
      combined with live imaging and drug treatment of muscle disease models, should
      allow for new elegant studies demonstrating how pharmacological approaches might
      influence inflammation and the immune response in muscle disease.

PMID- 24931443
TI  - Dynamic analysis of oral Candida carriage, distribution, and antifungal
      susceptibility in HIV-infected patients during the first year of highly active
      antiretroviral therapy in Guangxi, China.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) as an effective therapy
      for immune reconstruction among patients with HIV/AIDS might have influence on
      oral Candida status. We investigated oral Candida carriage, distribution, and
      antifungal susceptibility dynamically during the first year of HAART among adult
      HIV-infected patients in Guangxi, China. METHODS: Forty-five adult HIV-infected
      patients who received their first year HAART in the AIDS clinic of the Guangxi
      Center for Disease Control (CDC) and 31 healthy individuals were recruited.
      Clinical information and oral examinations were obtained. Oral rinses taken from
      patients at baseline, 3, 6, 12 months during HAART, respectively, were cultured,
      and Candida species were identified following standard microbiological
      techniques. In vitro antifungal susceptibilities were tested by the broth
      microdilution method. RESULTS: The oral Candida load decreased gradually in the
      45 patients with HIV/AIDS during the first year of HAART (P < 0.050). Among 176
      Candida isolates, Candida albicans (114/176) was the predominant species, and
      Candida parapsilosis (23/62) was the most common non-albicans species. We found
      the frequency of resistance to fluconazole and itraconazole of Candida isolated
      from our samples increased (P < 0.05) after 12 months of HAART. In addition, the
      frequency of C. albicans isolates resistant to fluconazole and itraconazole was
      on the rise (P < 0.05). CONCLUSIONS: The Candida load decreased with increased
      CD4(+) T cell counts, and C. albicans was still the prevailing species. Further,
      a trend toward more frequent in vitro resistance to fluconazole and itraconazole
      was observed. Our results provide reference for treatment and prevention of oral
      candidiasis among this population.

PMID- 24931442
TI  - Prevalence of atherogenic dyslipidemia in primary care patients at moderate-very
      high risk of cardiovascular disease. Cardiovascular risk perception.
AB  - INTRODUCTION: Atherogenic dyslipidemia is an important risk factor for
      cardiovascular disease. We aim to determine atherogenic dyslipidemia prevalence
      in primary care patients at moderate-very high cardiovascular risk and its
      associated cardiovascular risk perception in Spain. METHODS: This cross-sectional
      study included 1137 primary care patients. Patients had previous cardiovascular
      disease, diabetes mellitus, SCORE risk >= 3, severe hypertension or dyslipidemia.
      Atherogenic dyslipidemia was defined as low HDL-C (<40 mg/dL [males], <50 mg/dL
      [females]) and elevated triglycerides (>= 150 mg/dL). A visual analog scale was
      used to define a perceived cardiovascular disease risk score. RESULTS: Mean age
      was 63.9 +/- 9.7 years (64.6% males). The mean BMI was 29.1 +/- 4.3 kg/m(2), and
      mean waist circumference 104.2 +/- 12.7 cm (males), and 97.2 +/- 14.0 cm
      (females). 29.4% were smokers, 76.4% had hypertension, 48.0% were diabetics,
      24.7% had previous myocardial infarction, and 17.8% peripheral arterial disease.
      European guidelines classified 83.6% at very high cardiovascular risk.
      Recommended HDL-C levels were achieved by 50.1% of patients and 37.3% had
      triglycerides in the reference range. Target LDL-C was achieved by 8.8%. The
      overall atherogenic dyslipidemia prevalence was 27.1% (34.1% in diabetics). This
      prevalence in patients achieving target LDL-C was 21.4%. Cardiovascular risk
      perceived by patients was 4.3/10, while primary care physicians scored 5.7/10.
      CONCLUSIONS: When LDL-C levels are controlled, atherogenic dyslipidemia is more
      prevalent in those patients at highest cardiovascular risk and with diabetes.
      This highlights the importance of intervention strategies to prevent the residual
      vascular risk in this population. Both patients and physicians underestimated
      cardiovascular risk.

PMID- 24931444
TI  - Investigation of plateau methods for adsorption isotherm determination in
      supercritical fluid chromatography.
AB  - The Perturbation Peak (PP) method and Frontal analysis (FA) are considered as the
      most accurate methods for adsorption isotherms determination in liquid
      chromatography. In this study we investigate and explain why this is not the case
      in Supercritical Fluid Chromatography (SFC), where the PP method does not work at
      all, using a modern analytical system. The main reason was found to be that the
      solute to be studied must be dissolved in the MeOH reservoir before it is mixed
      with CO2. Since the solute occupies a certain partial volume in the reservoir,
      the larger the solute content the larger this fractional volume will be, and the
      final MeOH fraction in the mobile phase will then be smaller compared to the bulk
      mobile phase without solute in the modifier. If the retention of small injections
      on the concentration plateaus, i.e., "analytical-size" perturbation peaks, is
      sensitive to small variations of MeOH in the eluent, this will seriously decrease
      the accuracy of the PP method. This effect was verified and compensated for and
      we also demonstrated that the same problem will occur in frontal analysis,
      another concentration plateau method. 

PMID- 24931445
TI  - Inter-instrumental method transfer of chiral capillary electrophoretic methods
      using robustness test information.
AB  - Capillary electrophoresis (CE) is an electrodriven separation technique that is
      often used for the separation of chiral molecules. Advantages of CE are its
      flexibility, low cost and efficiency. On the other hand, the precision and
      transfer of CE methods are well-known problems of the technique. Reasons for the
      more complicated method transfer are the more diverse instrumental differences,
      such as total capillary lengths and capillary cooling systems; and the higher
      response variability of CE methods compared to other techniques, such as liquid
      chromatography (HPLC). Therefore, a larger systematic change in peak resolutions,
      migration times and peak areas, with a loss of separation and efficiency may be
      seen when a CE method is transferred to another laboratory or another type of
      instrument. A swift and successful method transfer is required because
      development and routine use of analytical methods are usually not performed in
      the same laboratory and/or on the same type of equipment. The aim of our study
      was to develop transfer rules to facilitate CE method transfers between different
      laboratories and instruments. In our case study, three beta-blockers were
      chirally separated and inter-instrumental transfers were performed. The first
      step of our study was to optimise the precision of the chiral CE method. Next, a
      robustness test was performed to identify the instrumental and experimental
      parameters that were most influencing the considered responses. The precision-
      and the robustness study results were used to adapt instrumental and/or method
      settings to improve the transfer between different instruments. Finally, the
      comparison of adapted and non-adapted transfers allowed deriving some rules to
      facilitate CE method transfers. 

PMID- 24931446
TI  - Hydrophilic interaction liquid chromatography as second dimension in
      multidimensional chromatography with an anionic trapping strategy: application to
      prostate-specific antigen quantification.
AB  - Liquid chromatography (LC) coupled with tandem mass spectrometry (MS-MS) in
      selected reaction monitoring mode (SRM) has become a widely used technique for
      the quantification of protein biomarkers in plasma and has already proven to give
      similar results compared to the conventional immunoassays. To improve the lack of
      insufficient sensitivity for quantification of low abundance protein, we propose
      a new two dimensional liquid chromatography (2D-LC-SRM) method for the
      quantitation of prostate specific antigen (PSA) in human plasma. The method
      centers on anion exchange cartridge between reversed-phase chromatography and
      hydrophilic interaction liquid chromatography (HILIC) in an on-line arrangement.
      The use of the anionic cartridge allows an easier online transfer of the analytes
      between both dimensions. Moreover, it provides an additional selectivity since
      the more basic peptides are not retained on this support. This setup has been
      applied to the quantification of prostate specific antigen (PSA) protein in
      plasma on a previous generation of mass spectrometer, which enabled a limit of
      quantification (LOQ) of 1ng/mL without any upfront immuno-depletion or intense
      off-line fractionation before the SRM analysis. The obtained LOQ is compatible
      with the required sensitivity for the clinically relevant plasma-based PSA tests.

PMID- 24931447
TI  - Information and complexity measures in molecular reactivity studies.
AB  - The analysis of the information and complexity measures as tools for the
      investigation of the chemical reactivity has been done in the spin-position and
      the position spaces, for the density and shape representations. The concept of
      the transferability and additivity of atoms or functional groups were used as
      "checkpoints" in the analysis of obtained results. The shape function as an
      argument of various measures reveals less information than the spinor density.
      Use of the shape function can yield wrong conclusions when the information
      measures such as the Shannon entropy (SE, S), the Fisher information (FI, I), the
      Onicescu information (OI, D), and complexities based on them are used for the
      systems with different electron numbers. Results obtained in the spinor-density
      representation show the transferability and additivity (while lacking in the case
      of the shape representation). The group transferability is well illustrated in
      the example of the X-Y molecules and their benzene derivatives. Another example
      is the methyl group transferability presented on the alkane-alkene-alkyne set.
      Analysis of the results displayed on planes between the three information
      theoretical (IT) based measures has shown that the S-I plane provides "richer"
      information about the pattern, organization, similarity of used molecules than
      the I-D and D-S planes. The linear relation of high accuracy is noted between the
      kinetic energy and the FI and the OI measures. Another interesting regression was
      found between the atomization total energy and the atomization entropy.
      Unfortunately, the lack of the group electronic energy transferability indicates
      that no general relations between the IT measures and the chemical reactivity
      indices are observed. The molecular set chosen for the study includes different
      types of molecules with various functional groups (19 groups). The used set is
      large enough (more than 700 molecules) and diverse to improve the previous
      understating of molecular complexities and to generalize obtained conclusions. 

PMID- 24931448
TI  - Biodegradation of marine surface floating crude oil in a large-scale field
      simulated experiment.
AB  - Biodegradation of marine surface floating crude oil with hydrocarbon degrading
      bacteria, rhamnolipid biosurfactants, and nutrients was carried out by a large
      scale field simulated experiment in this paper. After a 103 day experiment, for n
      alkanes, the maximum biodegradation rate reached 71% and the results showed
      hydrocarbon degrading bacteria, rhamnolipid biosurfactants, and nutrients have a
      comprehensive effect. It also showed that rhamnolipid biosurfactants could
      shorten the biodegradation time through an emulsifying function; the nutrients
      could greatly increase the biodegradation rate by promoting HDB production. For
      PAHs, the chrysene series had higher weathering resistance. For the same series,
      the weathering resistance ability is C1- < C2- < C3- < C4-. After 53 days, no
      comprehensive effect occurred and more biodegradation was found for different n
      alkanes in two pools which only had added rhamnolipid biosurfactants or
      nutrients, respectively. Except for C14, C15 and C16 sesquiterpanes, most of the
      steranes and terpanes had high antibiodegradability.

PMID- 24931449
TI  - SWNT nano-engineered networks strongly increase charge transport in P3HT.
AB  - We demonstrate the formation of arrays of 3D nanosized networks of interconnected
      single-wall carbon nanotubes (SWNTs) with well defined dimensions in a poly-3
      hexylthiophene (P3HT) thin film. These novel nanotube nano-networks produce
      efficient ohmic charge transport, even at very low nanotube loadings and low
      voltages. An increase in conductivity between one and two orders of magnitude is
      observed compared to a random network. The formation of these nano-engineered
      networks is compatible with large area imprinting and roll to roll processes,
      which makes it highly desirable for opto-electronic and energy conversion
      applications using carbon nanotubes. 

PMID- 24931450
TI  - The acute cognitive effects of zopiclone, zolpidem, zaleplon, and eszopiclone: a
      systematic review and meta-analysis.
AB  - The "z-drugs" zopiclone, zolpidem, eszopiclone, and zaleplon were introduced in
      the 1980s for the treatment of insomnia, as it was observed that the side effect
      profile associated with these medications were more benign than those related to
      the benzodiazepines. This meta-analysis set out to ascertain which domains of
      cognitive function, if any, were affected by the ingestion of these medications.
      A total of 20 studies met the study inclusion criteria. Results revealed medium
      effect sizes for zopiclone and zolpidem on measures of verbal memory. An
      additional medium effect size was observed for zolpidem on attention. Finally,
      smaller effect sizes were observed for zolpidem speed of processing and for
      zopiclone on working memory. It is clear from these data that the use of a single
      dose of the z-drugs in healthy adults as measured in the morning following the
      exposure does produce a specific rather than a generalized negative effect on
      cognitive function. However, there were only enough studies to evaluate the
      individual cognitive effects of the zolpidem and zopiclone medications; the
      specific effects of zaleplon and eszopiclone cannot be ascertained because only
      one study met the inclusion and exclusion criteria for the review. 

PMID- 24931451
TI  - Diagnostic performance of the Xpert MTB/RIF assay for tuberculous lymphadenitis
      on fine needle aspirates from Ethiopia.
AB  - The Xpert MTB/RIF (Xpert) test is a novel automated molecular diagnostic recently
      endorsed by the World Health Organization for rapid diagnosis of tuberculosis
      (TB). Nevertheless, performance related data from high TB prevalence regions to
      investigate clinically suspected TB lymphadenitis are limited. To evaluate the
      performance of Xpert test for direct detection of the Mycobacterium tuberculosis
      complex (MTBC) and rifampicin (RIF) resistance in lymph node aspirates, a cross
      sectional study was conducted at four main hospitals in northern Ethiopia.
      Culture served as a reference standard for growth of MTBC and phenotypic and
      MTBDRplus drug susceptibility testing for detecting RIF resistance. Two-hundred
      thirty-one fine needle aspirate (FNAs) specimens were processed simultaneously
      for smear, culture, and Xpert test. When compared to culture, the Xpert test
      correctly identified 29 out of 32 culture positive cases, 5 out of 11
      contaminated cases, and 56 out of 188 culture negative cases. The overall
      sensitivity of the test was 93.5% [95% CI, 78.3-98.9%] and specificity 69.2% [95%
      CI, 66.4-70.0%]. The Xpert test identified the rpoB mutations associated with RIF
      resistance concordant with GenoType MTBDRplus and phenotypic drug susceptibility
      testing. In conclusion, the Xpert assay was found to perform well in detecting
      MTBC and RIF resistance in TB lymphadenitis patients. Furthermore, the test is
      simple and suitable to use in remote and rural areas for the diagnosis of TB
      lymphadenitis directly from FNAs in Ethiopia where TB/MDR-TB is rampant. 

PMID- 24931454
TI  - Umbilical cord prolapse--changing patterns and improved outcomes: a retrospective
      cohort study.
AB  - OBJECTIVE: Umbilical cord prolapse is an acute obstetrical emergency requiring
      rapid identification and intervention. Its management has undergone significant
      changes over the past century. This study aims to document the changes in
      incidence, morbidity, and perinatal mortality over a 69-year period. DESIGN: A
      retrospective review of the annual clinical reports of the National Maternity
      Hospital, Dublin, Ireland, was performed. SETTING: The National Maternity
      hospital was founded in 1894 and has nearly 10,000 deliveries each year.
      POPULATION: All deliveries in the hospital for each year are included in each
      annual report. METHODS: We reviewed the reports from a 69-year period (1940
      2009). Information from the reports was collated into a database and analysed
      using Microsoft excel 2007. MAIN OUTCOME MEASURES: Incidence and outcome of all
      cases of umbilical cord prolapse were recorded, along with the neurological
      outcome of all neonatal survivors (available since 1970). RESULTS: The incidence
      of cord prolapse has decreased from 6.4/1000 live births in the 1940s to 1.7/1000
      [corrected] live births in the last decade. Perinatal survival increased from 46
      to 94% in the same period of time. This is inversely related to the use of
      caesarean section as the recommended method of delivery in this emergency. Short-
      and long-term neurological impairment remains rare. CONCLUSIONS: There has been a
      large reduction in the incidence of cord prolapse over a period of 69 years. A
      reduction in grand multiparity and use of caesarean section as the gold standard
      for delivery are likely to have accounted for the changes seen. Neurological
      impairment remains unusual.

PMID- 24931452
TI  - Class II human leucocyte antigen DRB1*11 in hairy cell leukaemia patients with
      and without haemolytic uraemic syndrome.
AB  - Frequencies of human leucocyte antigens (HLA) were determined in 287 classic
      hairy cell leukaemia (HCL) patients. With respect to both population (n = 287)
      and allele (2n = 574) frequency respectively, the most common HLA class I and II
      antigens expressed were HLA-A*02 (49.1% and 28.6%), HLA-B*07 (21.3% and 11.1%),
      HLA-C*07 (46.7 and 28.2%), HLA-DQB1*03 (62.7% and 37.3%), HLA-DRB1*11 (30.0% and
      16.0%) and HLA-DRB4*01 (45.3% and 29.6%). In comparing 6-14 databases of control
      Caucasians to 267 Caucasian HCL patients, only HLA-DRB1*11 was consistently over
      represented in HCL, 31.1% of patients vs. 17-19.9% of controls (P = 0.0055 to
      <0.0001) and 16.5% of alleles vs. 6.5-12.3% of control alleles (P = 0.022 to
      <0.0001). HLA-DRB1*11 is a known risk factor for acquired thrombotic
      microangiopathy. Anti-CD22 recombinant immunotoxin BL22 in HCL was associated
      with a 12% incidence of completely reversible grade 3-4 haemolytic uraemic
      syndrome (HUS), mainly during the second or third retreatment cycle. Of 49 HCL
      patients receiving >=2 cycles of BL22, 7 (14%) had HUS and HLA-DRB1*11 was
      expressed in 71% of 7 with HUS compared with only 21% of 42 without (P = 0.015).
      These data suggest that DBR1*11 may be a marker for increased susceptibility to
      HCL and, among HCL patients, could be a risk factor for BL22-induced HUS.

PMID- 24931455
TI  - Extracorporeal membrane oxygenation in pediatric organ donation.

PMID- 24931457
TI  - Variants in nicotinamide adenine dinucleotide phosphate oxidase complex
      components determine susceptibility to very early onset inflammatory bowel
      disease.
AB  - BACKGROUND & AIMS: The colitis observed in patients with very early onset
      inflammatory bowel disease (VEOIBD; defined as onset of disease at younger than 6
      years of age) often resembles that of chronic granulomatous disease (CGD) in
      extent and features of colonic inflammation observed by endoscopy and histology.
      CGD is a severe immunodeficiency caused by defects in the genes that encode
      components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      complex. We investigated whether variants in genes that encode NADPH oxidase
      components affect susceptibility to VEOIBD using independent approaches. METHODS:
      We performed targeted exome sequencing of genes that encode components of NADPH
      oxidases (cytochrome b light chain and encodes p22(phox) protein; cytochrome b
      245 or NADPH oxidase 2, and encodes Nox2 or gp91(phox); neutrophil cytosol factor
      1 and encodes p47 (phox) protein; neutrophil cytosol factor 2 and encodes p67
      (phox) protein; neutrophil cytosol factor 4 and encodes p40 (phox) protein; and
      Ras-related C3 botulinum toxin substrate 1 and 2) in 122 patients with VEOIBD
      diagnosed at The Hospital for Sick Children, University of Toronto, from 1994
      through 2012. Gene variants were validated in an independent International Early
      Onset Pediatric IBD Cohort Study cohort of patients with VEOIBD. In a second
      approach, we examined Tag single nucleotide polymorphisms in a subset of patients
      with VEOIBD in which the NOX2 NADPH oxidase genes sequence had been previously
      analyzed. We then looked for single nucleotide polymorphisms associated with the
      disease in an independent International Early Onset Pediatric IBD Cohort Study
      cohort of patients. We analyzed the functional effects of variants associated
      with VEOIBD. RESULTS: Targeted exome sequencing and Tag single nucleotide
      polymorphism genotyping identified 11 variants associated with VEOIBD; the
      majority of patients were heterozygous for these variants. Expression of these
      variants in cells either reduced oxidative burst or altered interactions among
      proteins in the NADPH oxidase complex. Variants in the noncoding regulatory and
      splicing elements resulted in reduced levels of proteins, or expression of
      altered forms of the proteins, in blood cells from VEOIBD patients. CONCLUSIONS:
      We found that VEOIBD patients carry heterozygous functional hypomorphic variants
      in components of the NOX2 NADPH oxidase complex. These do not cause overt
      immunodeficiency, but instead determine susceptibility to VEOIBD. Specific
      approaches might be developed to treat individual patients based on their genetic
      variant.

PMID- 24931456
TI  - A microRNA 221- and 222-mediated feedback loop maintains constitutive activation
      of NFkappaB and STAT3 in colorectal cancer cells.
AB  - BACKGROUND & AIMS: Constitutive activation of the transcription factors nuclear
      factor kappaB (NF-kappaB) and STAT3 is involved in the development and
      progression of human colorectal cancer (CRC). Little is known about how these
      factors become activated in cancer cells. We investigated whether microRNA miR
      221 and miR-222 regulate NF-kappaB and signal transducer and activator of
      transcription 3 (STAT3) activation in human CRC cell lines. METHODS: CRC cell
      lines (HCT116 and RKO) were transfected with miR-221 or miR-222 mimics or
      inhibitors. The activity levels of NF-kappaB and STAT3 were measured in dual
      luciferase reporter assays. We used immunoblot and real-time polymerase chain
      reaction analyses to measure protein and messenger RNA (mRNA) levels. Cells were
      analyzed by proliferation, viability, and flow cytometry analyses. Mice were
      given injections of azoxymethane, followed by dextran sodium sulfate, along with
      control lentivirus or those expressing mRNAs that bind miR-221 and miR-222 (miR
      221/miR-222 sponge). The levels of miR-221 and miR-222 as well as RelA, STAT3,
      and PDLIM2 mRNAs were measured in 57 paired CRC and adjacent nontumor tissues
      from patients. RESULTS: In CRC cell lines, mimics of miR-221 and miR-222
      activated NF-kappaB and STAT3, further increasing expression of miR-221 and miR
      222. miR-221 and miR-222 bound directly to the coding region of RelA mRNA,
      increasing its stability. miR-221 and miR-222 also reduced the ubiquitination and
      degradation of the RelA and STAT3 proteins by binding to the 3' untranslated
      region of PDLIM2 mRNA (PDLIM2 is a nuclear ubiquitin E3 ligase for RelA and
      STAT3). Incubation of CRC cells with miR-221 and miR-222 inhibitors reduced their
      proliferation and colony formation compared with control cells. In mice with
      colitis, injection of lentiviruses expressing miR-221/miR-222 sponges led to
      formation of fewer tumors than injection of control lentiviruses. Human CRC
      tissues had higher levels of miR-221 and miR-222 than nontumor colon tissues;
      increases correlated with increased levels of RelA and STAT3 mRNAs. Levels of
      PDLIM2 mRNA were lower in CRC than nontumor tissues. CONCLUSIONS: In human CRC
      cells, miR-221 and miR-222 act in a positive feedback loop to increase expression
      levels of RelA and STAT3. Antagonism of miR-221 and miR-222 reduces growth of
      colon tumors in mice with colitis.

PMID- 24931459
TI  - Demand for emergency department services in the elderly: an 11 year analysis of
      the Greater Sydney Area.
AB  - OBJECTIVE: To describe trends in population-based rates of ED presentations in
      the Greater Sydney Area (GSA) and compare these between the elderly and non
      elderly age groups. METHODS: This was a retrospective study using ED presentation
      data from all public hospitals in the GSA and population data from the Australian
      Bureau of Statistics between 2001 and 2011. Age-specific ED presentation rates
      stratified by age group (<65 years, 65-79 years and >=80 years of age) were
      presented and compared using negative binomial regression and generalised linear
      regression models. RESULTS: Over 11 million ED presentations were analysed. The
      annualised rate of increase in ED presentations per 1000 population was 1.8% per
      annum. The adjusted incidence rate ratio for patients aged 80 years and over was
      3.6 times higher than patients younger than 65 years (95% CI 2.8, 4.7, P < 0.001)
      and 1.6 times higher for patients between 65 and 79 years of age (95% CI 1.4,
      1.8, P < 0.001). There was an increase of 40 patients per 1000 population per
      year admitted to hospital from ED (beta = 40, 95% CI 29, 52 P < 0.001) in
      patients aged 80 years or older compared with those aged less than 65 years of
      age. CONCLUSIONS: A disproportionate increase in ED presentation rates and in
      patient admission rates in patients aged 80 years and over was demonstrated over
      11 years in the GSA. ED models of care and system wide strategies to address
      these demographic changes are required.

PMID- 24931458
TI  - Etiology of leukocyte adhesion deficiency-associated periodontitis revisited: not
      a raging infection but a raging inflammatory response.
AB  - In leukocyte adhesion deficiency type I, neutrophils fail to adhere to blood
      vessel walls and thus cannot transmigrate to peripheral tissues. Leukocyte
      adhesion deficiency type I patients invariably experience an aggressive form of
      generalized periodontitis, which has been historically attributed to defective
      neutrophil surveillance of the periodontal infection. This time-honored notion
      has now been challenged by a recent study, which showed that the underlying
      etiology involves a dysregulated host response that leads to overexpression of
      the proinflammatory and bone-resorptive cytokine IL-17. 

PMID- 24931460
TI  - Loeffler's syndrome: an interesting case report.
AB  - Loeffler's syndrome is an acute pneumonia with an unclear cause. One fourth of
      Loeffler's syndrome patients are idiopathic, although the most common etiologic
      causes include parasites. Asymptomatic form is usually a reversible, self-limited
      disease, which does not require a specific treatment regimen. We presented a 17
      year-old young man with diagnosis of Loeffler syndrome. 

PMID- 24931461
TI  - Pilot study using tacrolimus rather than cyclosporine plus antithymocyte globulin
      as an immunosuppressive therapy regimen option for severe aplastic anemia in
      adults.
AB  - Severe aplastic anemia (SAA), which is considered to be an immune-mediated
      destruction of bone marrow stem cells with pancytopenia and hypoplasia, can be
      successfully treated with immunosuppressive therapy or hematopoietic stem cell
      transplantation (HSCT). Between January 2009 and December 2012, thirteen patients
      diagnosed with SAA were treated with tacrolimus plus rabbit antithymocyte
      globulin (ATG)-based immunosuppressive therapy (IST). The outcomes were then
      compared with our previous data for twenty-four patients administered with
      cyclosporine (CsA) plus rabbit ATG-based IST. All 37 cases accepted
      methylpredenisolone and recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) from the first day that rabbit ATG was initiated. A total of 7 (54%) of
      the 13 patients in the tacrolimus group and 10 (42%) of the 24 cases in the
      ATG+CsA group achieved the criteria for complete response (CR); the partial
      response (PR) rate was 31% in the tacrolimus group and 33% in the ATG+CsA group.
      The median follow-up duration of the tacrolimus group and ATG+CsA group patients
      was 28 months and 27 months, respectively. Two patients in the tacrolimus group
      who were red blood cell- and platelet transfusion-dependent died, one of sepsis
      and the other of cerebral hemorrhage, whereas one patient died from serious
      infection on the 5th day after ATG was initiated in the ATG+CsA group. No clonal
      transformation to paroxysmal nocturnal hemoglobinuria (PNH) was observed in
      either group. Our data provide a possibility of using tacrolimus as part of an
      IST regimen for SAA in adults who have no opportunity of HSCT from human
      leukocyte antigen (HLA)-matched sibling donors.

PMID- 24931463
TI  - Intramolecular halogen bonding supported by an aryldiyne linker.
AB  - Intramolecular halogen bonds between aryl halide donors and suitable acceptors,
      such as carbonyl or quinolinyl groups, held in proximity by 1,2-aryldiyne
      linkers, provide triangular structures in the solid state. Aryldiyne linkers
      provide a nearly ideal template for intramolecular halogen bonding as minor
      deviations from alkyne linearity can accommodate a variety of halogen bonding
      interactions, including O...Cl, O...Br, O...I, N...Br, and N...I. Halogen bond
      lengths for these units, observed by single crystal X-ray crystallography, range
      from 2.75 to 2.97 A. Internal bond angles of the semirigid bridge between halogen
      bond donor and acceptor are responsive to changes in the identity of the halogen,
      the identity of the acceptor, and the electronic environment around the halogen,
      with the triangles retaining almost perfect co-planarity in even the most
      strained systems. Consistency between experimental results and structures
      predicted by M06-2X/6-31G* calculations demonstrates the efficacy of this
      computational method for modeling halogen-bonded structures of this type. 

PMID- 24931462
TI  - Rhodium-catalyzed direct coupling of biaryl pyridine derivatives with internal
      alkynes.
AB  - Axially chiral biaryls were synthesized by an isoquinoline or 2-pyridine-directed
      Rh(III)-catalyzed dual C-H cleavage and coupling with internal alkynes in good to
      excellent yields. Oxidation of isoquinoline derivatives with m-CPBA furnished
      their corresponding N-oxides, which could be utilized as Lewis base catalysts in
      asymmetric reactions.

PMID- 24931464
TI  - Low expression of microRNA-146b-5p and microRNA-320d predicts poor outcome of
      large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine,
      and prednisone.
AB  - Although diffuse large B-cell lymphoma (DLBCL) encompasses a biologically and
      clinically diverse set of diseases, increasing evidence has pointed to an
      important role of microRNAs (miRs) in the pathogenesis of DLBCL. We report here
      that low expression of miR-146b-5p and miR-320d is associated with poor prognosis
      of DLBCL patients treated with the standard cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP) regimen and that this is related to the
      inhibitory effect of these miRs on DLBCL cell proliferation. Analysis of a
      retrospective cohort of 106 primary nodal DLBCL samples from patients who were
      treated with CHOP showed that, when the median survival period (40.8 months) was
      used as the cutoff point, miR-146b-5p and miR-320d were expressed at lower levels
      in DLBCLs with poor prognosis. Indeed, whereas low expression of miR-146b-5p was
      correlated with reduced progression-free survival, low expression of miR-320d was
      associated with decreases in both progression-free survival and overall survival.
      Moreover, miR-146b-5p and miR-320d were expressed at significantly lower levels
      in DLBCLs with the MYC t(8;14) translocation. Functional studies demonstrated
      that overexpression of miR-146b-5p or miR-320d inhibited DLBCL cell
      proliferation, wheareas knockdown of miR-146b-5p or miR-320d promoted
      proliferation of DLBCL cells. Taken together, these results suggest that low
      expression of miR-146b-5p and miR-320d may be predictive of compromised responses
      of a subset of DLBCL patients to treatment with the CHOP regimen and that
      restoration of these miRs may be useful to improve the therapeutic efficacy of
      CHOP.

PMID- 24931465
TI  - Multifocal kaposiform hemangioendothelioma in multiple visceral organs: an
      autopsy of 9-day-old female baby.
AB  - Kaposiform hemangioendothelioma is a vascular tumor categorized as intermediate
      malignancy. We experienced an autopsy of a female baby with kaposiform
      hemangioendothelioma with Kasabach-Merritt syndrome. She died of systemic
      bleeding tendency following disseminated intravascular coagulation at the age of
      9 days. At autopsy, a huge main tumor, histologically kaposiform
      hemangioendothelioma, was discovered in the mediastinum between the right chest
      cavity and pericardium. Furthermore, kaposiform hemangioendothelioma with the
      same histology involved the lungs, heart, liver, subserosa of cardial part of the
      stomach, retroperitoneum around the right adrenal gland, broad ligament of the
      uterus, and muscular tissue around the thyroid. To date, a few previously
      reported cases of multifocal kaposiform hemangioendothelioma have demonstrated
      locally aggressive distributions mainly in bone and soft tissues. The present
      case with extensive distribution including visceral organs implies that
      kaposiform hemangioendothelioma may have higher potential to spread than
      considered before.

PMID- 24931466
TI  - Changing prognostic factors in osteosarcoma: analysis of 381 cases from two
      institutions.
AB  - Osteosarcoma occurs most commonly in children and young adults, with a historic
      second incidence peak in the elderly. Most studies have focused on those
      occurring in adolescence. Detailed information on descriptive features and
      prognostic factors in patients of different age groups is lacking. We analyzed
      381 osteosarcomas diagnosed between 1973 and 2012 to identify factors
      significantly associated with survival in various age groups. The peak incidence
      was seen in patients age <25, followed by a steady incidence rate thereafter
      until the sixth decade, when it started to decline. In the early onset diseases,
      significant factors for recurrence-free survival (RFS) were tumor site and size;
      whereas those for overall survival (OS) were gender, tumor site, type, grade and
      size. In patients age 25 to 54, tumor type and grade were significant for RFS,
      and the pathologic type was significant for OS. In those age >=55, race and tumor
      size were significant for RFS; tumor site and size were significant for OS. In
      multivariate analysis, tumor size remained significant for RFS; gender, tumor
      site and size maintained their significance for OS in patients age <25. While no
      independent factor was identified in patients age 25 to 54, tumor size remained
      significant for RFS in those age >=55. Chemotherapy-induced tumor necrosis was a
      prognosticator for RFS in patients age 25 to 54 by univariate analysis, but not
      as an independent factor in any stratified age group. Our data indicate that the
      distinctive prognostic factors differed significantly among different age groups,
      thus providing a rationale for age-based management strategies.

PMID- 24931467
TI  - Spontaneous self-assembly of engineered armadillo repeat protein fragments into a
      folded structure.
AB  - Repeat proteins are built of modules, each of which constitutes a structural
      motif. We have investigated whether fragments of a designed consensus armadillo
      repeat protein (ArmRP) recognize each other. We examined a split ArmRP consisting
      of an N-capping repeat (denoted Y), three internal repeats (M), and a C-capping
      repeat (A). We demonstrate that the C-terminal MA fragment adopts a fold similar
      to the corresponding part of the entire protein. In contrast, the N-terminal YM2
      fragment constitutes a molten globule. The two fragments form a 1:1 YM2:MA
      complex with a nanomolar dissociation constant essentially identical to the
      crystal structure of the continuous YM3A protein. Molecular dynamics simulations
      show that the complex is structurally stable over a 1 MUs timescale and reveal
      the importance of hydrophobic contacts across the interface. We propose that the
      existence of a stable complex recapitulates possible intermediates in the early
      evolution of these repeat proteins.

PMID- 24931468
TI  - Internal lipid architecture of the hetero-oligomeric cytochrome b6f complex.
AB  - The role of lipids in the assembly, structure, and function of hetero-oligomeric
      membrane protein complexes is poorly understood. The dimeric photosynthetic
      cytochrome b6f complex, a 16-mer of eight distinct subunits and 26 transmembrane
      helices, catalyzes transmembrane proton-coupled electron transfer for energy
      storage. Using a 2.5 A crystal structure of the dimeric complex, we identified 23
      distinct lipid-binding sites per monomer. Annular lipids are proposed to provide
      a connection for super-complex formation with the photosystem-I reaction center
      and the LHCII kinase enzyme for transmembrane signaling. Internal lipids mediate
      crosslinking to stabilize the domain-swapped iron-sulfur protein subunit,
      dielectric heterogeneity within intermonomer and intramonomer electron transfer
      pathways, and dimer stabilization through lipid-mediated intermonomer
      interactions. This study provides a complete structure analysis of lipid-mediated
      functions in a multi-subunit membrane protein complex and reveals lipid sites at
      positions essential for assembly and function.

PMID- 24931471
TI  - Implementation of nuclear gradients of range-separated hybrid density functionals
      and benchmarking on rotational constants for organic molecules.
AB  - We have implemented the nuclear gradient for several range-separated hybrid
      density functionals in the general quantum chemistry code ORCA. To benchmark the
      performance, we have used a recently published set of back-corrected gas phase
      rotational constants, which we extended by three molecules. In our evaluation,
      CAM-B3LYP-D3 and omegaB97X-D3 show great accuracy, and are surpassed by B2PLYP-D3
      only. Lower-cost alternatives to quadruple-zeta basis set-based calculations,
      among them a smaller basis set and the use of resolution-of-the-identity
      approaches, are assessed and shown to yield acceptable deviations. In addition,
      the Hartree-Fock-based back-correction method is compared to a density functional
      theory alternative, which largely shows consistency between the two. A new, well
      performing, spin-component scaled MP2 variant is designed and discussed, as well.

PMID- 24931469
TI  - Molecular basis of substrate recognition and degradation by human presequence
      protease.
AB  - Human presequence protease (hPreP) is an M16 metalloprotease localized in
      mitochondria. There, hPreP facilitates proteostasis by utilizing an ~13,300-A(3)
      catalytic chamber to degrade a diverse array of potentially toxic peptides,
      including mitochondrial presequences and beta-amyloid (Abeta), the latter of
      which contributes to Alzheimer disease pathogenesis. Here, we report crystal
      structures for hPreP alone and in complex with Abeta, which show that hPreP uses
      size exclusion and charge complementation for substrate recognition. These
      structures also reveal hPreP-specific features that permit a diverse array of
      peptides, with distinct distributions of charged and hydrophobic residues, to be
      specifically captured, cleaved, and have their amyloidogenic features destroyed.
      SAXS analysis demonstrates that hPreP in solution exists in dynamic equilibrium
      between closed and open states, with the former being preferred. Furthermore,
      Abeta binding induces the closed state and hPreP dimerization. Together, these
      data reveal the molecular basis for flexible yet specific substrate recognition
      and degradation by hPreP.

PMID- 24931472
TI  - Editorial: phytochemicals, intracellular signalling pathways and anti-cancer
      effects.

PMID- 24931470
TI  - CD4-induced activation in a soluble HIV-1 Env trimer.
AB  - The HIV envelope glycoprotein (Env) trimer undergoes receptor-induced
      conformational changes that drive fusion of the viral and cellular membranes. Env
      conformational changes have been observed using low-resolution electron
      microscopy, but only large-scale rearrangements have been visible. Here, we use
      hydrogen-deuterium exchange and oxidative labeling to gain a more precise
      understanding of the unliganded and CD4-bound forms of soluble Env trimers
      (SOSIP.664), including their glycan composition. CD4 activation induces the
      reorganization of bridging sheet elements, V1/V2 and V3, much of the gp120 inner
      domain, and the gp41 fusion subunit. Two CD4 binding site-targeted inhibitors
      have substantially different effects: NBD-556 partially mimics CD4-induced
      destabilization of the V1/V2 and V3 crown, whereas BMS-806 only affects regions
      around the gp120/gp41 interface. The structural information presented here
      increases our knowledge of CD4- and small molecule-induced conformational changes
      in Env and the allosteric pathways that lead to membrane fusion.

PMID- 24931473
TI  - Endothelial Delta-like 4 (DLL4) promotes renal cell carcinoma hematogenous
      metastasis.
AB  - The Notch ligand Delta-like 4 (DLL4) plays an important role in tumor
      angiogenesis, which is required for tumor invasion and metastasis. Here we showed
      that DLL4 was elevated in endothelium and Notch signaling was activated in renal
      cell carcinoma (RCC). Exogenous DLL4 induced RCC cell migration and invasion by
      activating intercellular Notch signaling. Importantly, the DLL4/Notch/Hey1/MMP9
      cascades connecting the endothelium to the cancer cells in metastasis were
      identified. Knockdown of Hey1 decreased expression of MMP9 and attenuated tumor
      invasion. The clinical investigation on 120 cases of RCC specimens indicated that
      expressions of Hey1 and MMP9 correlated with DLL4 density. Moreover, univariate
      and multivariate analyses showed that tumor hematogenous metastasis not only was
      depended on microvessel density but was also associated with tumor size and DLL4
      density. During 4-year surveillance, high-level of DLL4 density was associated
      with a higher probability of developing metastasis and being sensitive to target
      therapies. Our data suggest that RCC progression is caused in part by activated
      DLL4/Notch signaling, interaction of endothelium and cells, which can be
      therapeutically targeted. 

PMID- 24931474
TI  - Maternal adaptations in preparation for parturition predict uncomplicated
      spontaneous delivery outcome.
AB  - OBJECTIVE: The objective of the study was to define maternal tissue adaptations
      in pregnancy associated with uncomplicated spontaneous vaginal delivery using
      anatomical and biological outcomes. STUDY DESIGN: Nulliparous gravidas were
      prospectively enrolled in the first trimester at 2 institutions. Demographic and
      delivery data were chart abstracted. Vaginal elastase activity (units per
      milligram of protein) and Pelvic Organ Prolapse Quantification measurements of
      pelvic organ support were obtained in the first and third trimesters. A subset
      underwent 3-dimensional ultrasound measures of levator hiatus. Uncomplicated
      spontaneous vaginal delivery (VD) was defined as no cesarean, forceps, vacuum,
      shoulder dystocia, third- or fourth-degree perineal laceration, or prolonged
      second stage labor. RESULTS: We enrolled 173 women in their first trimester, 50
      of whom had ultrasounds. Mean age was 25.5 +/- 5.5 years with a body mass index
      of 28.0 +/- 7.3 kg/m(2). Sixty-seven percent were white/Caucasian, 27%
      black/African American, and 6% Hispanic/Latina. Mean delivery gestational age was
      38.5 +/- 2.9 weeks, with 23% delivering by cesarean and 59% achieving
      uncomplicated spontaneous VD. Vaginal support changed significantly over
      trimesters with posterior vaginal and hiatal relaxation, vaginal lengthening, and
      increased levator hiatus area during strain. Women achieving uncomplicated
      spontaneous VD demonstrated significantly greater relaxation on third-trimester
      Pelvic Organ Prolapse Quantification for anterior, apical, and hiatal measures
      than those without uncomplicated spontaneous VD. Higher first-trimester vaginal
      elastase activity was strongly associated with uncomplicated spontaneous VD
      (geometric mean activity 0.289 +/- 0.830 U/mg vs -0.029 +/- 0.585 U/mg, P =
      .009). Higher first-trimester elastase, younger age, lower first-trimester body
      mass index, and more third-trimester vaginal support laxity in points C and GH
      were predictive of VD success. CONCLUSION: Significant maternal adaptations occur
      in the vagina during pregnancy, presumably in preparation for vaginal delivery.
      Greater adaptation, including vaginal descent and higher first-trimester elastase
      activity, is associated with an increased likelihood of uncomplicated spontaneous
      VD.

PMID- 24931475
TI  - A comparison of Doppler and biophysical findings between liveborn and stillborn
      growth-restricted fetuses.
AB  - OBJECTIVE: The purpose of this study was to evaluate the surveillance
      characteristics that precede stillbirth in growth-restricted fetuses that receive
      integrated Doppler and biophysical profile scoring (BPS). STUDY DESIGN: Nine
      hundred eighty-seven singleton pregnancies that were complicated by fetal growth
      restriction had multivessel Doppler scans (umbilical and middle cerebral arteries
      [MCA], ductus venosus, and umbilical vein) and BPS. Surveillance findings were
      compared between live births and stillbirths. RESULTS: Forty-seven stillbirths
      occurred in 2 clusters, 37 at <34 weeks of gestation and 10 thereafter. Before 34
      weeks of gestation, stillbirths had parallel escalation of umbilical artery and
      ductus venosus Doppler findings followed by abnormal BPS. At >=34 weeks of
      gestation, only a decline in MCA pulsatility index was observed, and 75% of
      stillbirths were unanticipated by the BPS. CONCLUSION: Before 34 weeks of
      gestation, multivessel Doppler abnormality anticipates an abnormal BPS and
      subsequent stillbirth. After 34 weeks of gestation, stillbirths occur after MCA
      brain-sparing in a shorter interval than predicted by a normal BPS. Recognition
      of these differences in clinical behavior requires consideration for the planning
      of monitoring intervals in preterm and term fetal growth restriction.

PMID- 24931476
TI  - Declaration on mental health in Africa: moving to implementation.
AB  - Urgent action is needed to address mental health issues globally. In Africa,
      where mental health disorders account for a huge burden of disease and
      disability, and where in general less than 1% of the already small health budgets
      are spent on these disorders, the need for action is acute and urgent. Members of
      the World Health Organization, including African countries, have adopted a
      Comprehensive Mental Health Action Plan. Africa now has an historic opportunity
      to improve the mental health and wellbeing of its citizens, beginning with
      provision of basic mental health services and development of national mental
      health strategic plans (roadmaps). There is need to integrate mental health into
      primary health care and address stigma and violations of human rights. We
      advocate for inclusion of mental health into the post-2015 Sustainable
      Development Goals, and for the convening of a special UN General Assembly High
      Level Meeting on Mental Health within three years. 

PMID- 24931477
TI  - Sex differences in lifting strategies during a repetitive palletizing task.
AB  - Forty-five manual material handlers (15 females, 15 expert males and 15 novice
      males) performed series of box transfers under conditions similar to those of
      large distribution centers. The objective of the study was to verify whether sex
      differences in joint motions and in back loading variables (L5/S1 moments) exist
      during multiple box transfers. The task consisted in transferring 24 15-kg boxes
      from one pallet to another (4 layers of boxes; 6 boxes/layer: 3 in the front row,
      3 in the back) at a self-determined pace and then at an imposed pace of 9
      lifts/min. Full-body 3D kinematic data were collected as well as external foot
      forces. A dynamic 3D linked segment model was used to estimate the net moments at
      L5/S1. The results show that the peak L5/S1 moment during lifting for females was
      significantly lower than for males, but once normalized to body size the
      difference disappeared. In general, the female workers were very close to the
      posture adopted by the novice males at the instant of the peak resultant moment.
      However, females were closer to the box than the male workers. One major sex
      difference was seen when lifting from the ground, with the use of interjoint
      coordination analyses. Female workers showed a sequential motion initiated by the
      knees, followed by the hip and the back, while expert males showed a more
      synchronized motion. The lifting strategy of females likely stretches lumbar
      spine passive tissues, which in turn put them at greater risk of back injuries.
      As observed in our previous studies, these differences between expert males,
      novice males and females are especially notable when the box is lifted from the
      ground. 

PMID- 24931478
TI  - Psychometric properties evaluation of a new ergonomics-related job factors
      questionnaire developed for nursing workers.
AB  - The objectives of this study were to develop a questionnaire that evaluates the
      perception of nursing workers to job factors that may contribute to
      musculoskeletal symptoms, and to evaluate its psychometric properties.
      Internationally recommended methodology was followed: construction of domains,
      items and the instrument as a whole, content validity, and pre-test. Psychometric
      properties were evaluated among 370 nursing workers. Construct validity was
      analyzed by the factorial analysis, known-groups technique, and convergent
      validity. Reliability was assessed through internal consistency and stability.
      Results indicated satisfactory fit indices during confirmatory factor analysis,
      significant difference (p < 0.01) between the responses of nursing and office
      workers, and moderate correlations between the new questionnaire and Numeric Pain
      Scale, SF-36 and WRFQ. Cronbach's alpha was close to 0.90 and ICC values ranged
      from 0.64 to 0.76. Therefore, results indicated that the new questionnaire had
      good psychometric properties for use in studies involving nursing workers. 

PMID- 24931479
TI  - Conserved evolutionary units in the heme-copper oxidase superfamily revealed by
      novel homologous protein families.
AB  - The heme-copper oxidase (HCO) superfamily includes HCOs in aerobic respiratory
      chains and nitric oxide reductases (NORs) in the denitrification pathway. The
      HCO/NOR catalytic subunit has a core structure consisting of 12 transmembrane
      helices (TMHs) arranged in three-fold rotational pseudosymmetry, with six
      conserved histidines for heme and metal binding. Using sensitive sequence
      similarity searches, we detected a number of novel HCO/NOR homologs and named
      them HCO Homology (HCOH) proteins. Several HCOH families possess only four TMHs
      that exhibit the most pronounced similarity to the last four TMHs (TMHs 9-12) of
      HCOs/NORs. Encoded by independent genes, four-TMH HCOH proteins represent a
      single evolutionary unit (EU) that relates to each of the three homologous EUs of
      HCOs/NORs comprising TMHs 1-4, TMHs 5-8, and TMHs 9-12. Single-EU HCOH proteins
      could form homotrimers or heterotrimers to maintain the general structure and
      ligand-binding sites defined by the HCO/NOR catalytic subunit fold. The remaining
      HCOH families, including NnrS, have 12-TMHs and three EUs. Most three-EU HCOH
      proteins possess two conserved histidines and could bind a single heme. Limited
      experimental studies and genomic context analysis suggest that many HCOH proteins
      could function in the denitrification pathway and in detoxification of reactive
      molecules such as nitric oxide. HCO/NOR catalytic subunits exhibit remarkable
      structural similarity to the homotrimers of MAPEG (membrane-associated proteins
      in eicosanoid and glutathione metabolism) proteins. Gene duplication, fusion, and
      fission likely play important roles in the evolution of HCOs/NORs and HCOH
      proteins. 

PMID- 24931480
TI  - Treatment of medically refractory cancer pain with a combination of intrathecal
      neuromodulation and neurosurgical ablation: case series and literature review.
AB  - OBJECTIVE: Up to 90% of patients with advanced cancer experience intractable
      pain. For these patients, oral analgesics are the mainstay of therapy, often
      augmented with intrathecal drug delivery. Neurosurgical ablative procedures have
      become less commonly used, though their efficacy has been well-established.
      Unfortunately, little is known about the safety of ablation in the context of
      previous neuromodulation. Therefore, the aim of this study is to present the
      results from a case series in which patients were treated successfully with a
      combination of intrathecal neuromodulation and neurosurgical ablation. DESIGN:
      Retrospective case series and literature review. SETTING: Three institutions with
      active cancer pain management programs in the United States. METHODS: All
      patients who underwent both neuroablative and neuromodulatory procedures for
      cancer pain were surveyed using the visual analog scale prior to the first
      procedure, before and after a second procedure, and at long-term follow-up. Based
      on initial and subsequent presentation, patients underwent intrathecal morphine
      pump placement, cordotomy, or midline myelotomy. RESULTS: Five patients (2 male,
      3 female) with medically intractable pain (initial VAS = 10) were included in the
      series. Four subjects were initially treated with intrathecal analgesic
      neuromodulation, and 1 with midline myelotomy. Each patient experienced
      recurrence of pain (VAS >= 9) following the initial procedure, and was therefore
      treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1;
      percutaneous radiofrequency cordotomy, N = 3), with significant long-term benefit
      (VAS 1-7). CONCLUSION: In cancer patients with medically intractable pain,
      intrathecal neuromodulation and neurosurgical ablation together may allow for
      more effective control of cancer pain.

PMID- 24931481
TI  - Towards mapping the brain connectome in depression: functional connectivity by
      perfusion SPECT.
AB  - Several studies have demonstrated altered brain functional connectivity in the
      resting state in depression. However, no study has investigated interregional
      networking in patients with persistent depressive disorder (PDD). The aim of this
      study was to assess differences in brain perfusion distribution and connectivity
      between large groups of patients and healthy controls. Participants comprised 91
      patients with PDD and 65 age- and sex-matched healthy controls. Resting state
      perfusion was investigated by single photon emission computed tomography, and
      group differences were assessed by Statistical Parametric Mapping. Brain
      connectivity was explored through a voxel-wise interregional correlation analysis
      using as covariate of interest the normalized values of clusters of voxels in
      which perfusion differences were found in group analysis. Significantly increased
      regional brain perfusion distribution covering a large part of the cerebellum was
      observed in patients as compared with controls. Patients showed a significant
      negative functional connectivity between the cerebellar cluster and caudate,
      bilaterally. This study demonstrated inverse relative perfusion between the
      cerebellum and the caudate in PDD. Functional uncoupling may be associated with a
      dysregulation between the role of the cerebellum in action control and of the
      caudate in action selection, initiation and decision making in the patients. The
      potential impact of the resting state condition and the possibility of
      mitochondrial impairment are discussed. 

PMID- 24931482
TI  - Association between fluid balance and survival in critically ill patients.
AB  - OBJECTIVE: Although the consequences of chronic fluid retention are well known,
      those of iatrogenic fluid retention that occurs during critical illness have not
      been fully determined. Therefore, we investigated the association between fluid
      balance and survival in a cohort of almost 16,000 individuals who survived an
      intensive care unit (ICU) stay in a large, urban, tertiary medical centre.
      DESIGN: Longitudinal analysis of fluid balance at ICU discharge and 90-day post
      ICU survival. MEASUREMENTS: Associations between fluid balance during the ICU
      stay, determined from the electronic bedside record, and survival were tested
      using Cox proportional hazard models adjusted for severity of critical illness.
      RESULTS: There were 1827 deaths in the first 90 days after ICU discharge.
      Compared with the lowest quartile of discharge fluid balance [median
      (interquartile range) -1.5 (-3.1, -0.7) L], the highest quartile [7.6 (5.7, 10.8)
      L] was associated with a 35% [95% confidence interval (CI) 1.13-1.61)] higher
      adjusted risk of death. Fluid balance was not associated with outcome amongst
      individuals without congestive heart failure or renal dysfunction. Amongst
      patients with either comorbidity, however, fluid balance was strongly associated
      with outcome, with the highest quartile having a 55% (95% CI 1.24-1.95) higher
      adjusted risk of death than the lowest quartile. Isotonic fluid balance, defined
      as the difference between intravenous isotonic fluid administration and urine
      output, was similarly associated with 90-day outcomes. CONCLUSION: Positive fluid
      balance at the time of ICU discharge is associated with increased risk of death,
      after adjusting for markers of illness severity and chronic medical conditions,
      particularly in patients with underlying heart or kidney disease. Restoration of
      euvolaemia prior to discharge may improve survival after acute illness.

PMID- 24931483
TI  - Editorial comment from Dr Yokomizo to efficacy of traditional and alternative
      sunitinib treatment schedules in Japanese patients with metastatic renal cell
      carcinoma.

PMID- 24931484
TI  - Existence of glia mitigated ketamine-induced neurotoxicity in neuron-glia mixed
      cultures of neonatal rat cortex and the glia-mediated protective effect of 2
      PMPA.
AB  - The present study compared ketamine-induced neurotoxicity in the neuron-glia
      mixed cultures and neuronal cultures and further explored the neuroprotective
      effect of the NAAG peptidase inhibitor 2-(phosphonomethyl) pentanedioic acid (2
      PMPA). Firstly, Rosenfeld's staining and immunofluorescence staining of
      microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein
      (GFAP) were used to address the difference of morphology in the mixed cultures
      and neuronal cultures. Our results showed that neurons and astrocytes grew in
      good conditions. The ratio of neurons and astrocytes in the mixed cultures was
      around 1:1, and the purity of neurons in the neuronal cultures is 91.3%.
      Furthermore, ketamine was used to test the hypothesis that the presence of a
      higher proportion of glia in the mixed cultures would be protective against
      ketamine-induced neurotoxicity in the mixed cultures compared with neuronal
      cultures. The results showed that ketamine-induced morphological changes, cell
      viability decrease and lactate dehydrogenase (LDH) levels increase were
      significantly mitigated in neuron-glia mixed cultures compared with neuronal
      cultures. Furthermore, 2-PMPA was included to further explore efficient
      protective drug for ketamine-induced neurotoxicity. Our results showed that 2
      PMPA reduced ketamine-induced decrease of cell viability and increase of LDH
      levels in the mixed cultures but not in the neuronal cultures. Further
      morphological changes of neurons and astrocytes also indicated that 2-PMPA could
      improve ketamine damaged neurons in the mixed cultures instead of neuronal
      cultures. These results indicate that glia protect neurons from ketamine-induced
      neurotoxicity. These data further suggest that glia mediate the neuroprotective
      effect of 2-PMPA and 2-PMPA has the potential to treat ketamine-induced
      neurotoxicity in vivo. Delineating the mechanisms underlying the communication
      between neurons and glia and the neuroprotective effects of 2-PMPA in the mixed
      cultures to ketamine-induced neurotoxicity require further investigation. 

PMID- 24931485
TI  - A strap strategy for construction of an excited-state intramolecular proton
      transfer (ESIPT) system with dual fluorescence.
AB  - An amine-embedded flexible alkyl strap has been incorporated into an emissive
      boryl-substituted dithienylpyrrole skeleton as a new entity of excited-state
      intramolecular proton transfer (ESIPT) chromophores. The pi-electron system shows
      a dual emission, which covers a wide range of the visible region depending on the
      solvent polarity. The incorporation of the aminoalkyl strap as well as the
      terminal boryl groups efficiently stabilize the zwitterionic excited-state
      species resulting from the ESIPT even in an aqueous medium. 

PMID- 24931486
TI  - Pathophysiology and Japanese clinical characteristics in Marfan syndrome.
AB  - Marfan syndrome is an autosomal dominant heritable disorder of the connective
      tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major
      component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts
      with transforming growth factor-beta (TGF-beta), and dysregulated TGF-beta
      signaling plays a major role in the development of connective tissue disease and
      familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an
      angiotensin II blocker, has the potential to reduce TGF-beta signaling and is
      expected to be an additional therapeutic option. Clinical diagnosis is made using
      the Ghent nosology, which requires comprehensive patient assessment and has been
      proven to work well, but evaluation of some of the diagnostic criteria by a
      single physician is difficult and time-consuming. A Marfan clinic was established
      at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac
      surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the
      purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In
      this review, we discuss the recent progress in diagnosis and treatment of Marfan
      syndrome, and the characteristics of Japanese patients with Marfan syndrome. 

PMID- 24931488
TI  - Anaphylaxis to diclofenac: nine cases reported to the Allergy Vigilance Network
      in France.
AB  - Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance
      Network in France from 2002 to 2012 were studied. Data from history, symptoms,
      skin tests, basophil activation tests, and oral challenge (OC) were recorded.
      Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE
      dependent anaphylaxis was confirmed in six cases: positive intradermal tests (n =
      4), a syndromic reaction during skin tests (n = 1), and one case with grade 1
      reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune
      reaction was suspected in one case. An IgE-dependent mechanism may be the
      predominant cause of adverse reactions to diclofenac. Allergy skin tests must be
      carried out sequentially at the recommended concentrations. BATs may be helpful
      because they can support the diagnosis of anaphylaxis. Given the risks of a
      direct challenge to diclofenac, OC to aspirin should be performed first to
      exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to
      most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed.

PMID- 24931487
TI  - Use of hormonal contraceptives among immigrant and native women in Norway: data
      from the Norwegian Prescription Database.
AB  - OBJECTIVE: To examine the use of hormonal contraceptives among immigrant and
      native women in Norway. DESIGN: Nationwide registry-based study based on merged
      data from the Norwegian Prescription Database, the Norwegian Population Registry,
      the Regular General Practitioner Database and the Medical Birth Registry.
      SETTING: Norway. SAMPLE: All women born abroad to two foreign-born parents
      (immigrants), or born in Norway to two Norwegian-born parents (natives) aged 16
      45 years, who lived in Norway in 2008. METHODS: Data on all collected supplies of
      hormonal contraceptives in 2008 were merged with demographic, socio-economic and
      immigration data, information on any delivery and women's general practitioners.
      MAIN OUTCOME MEASURES: User rates of hormonal contraception and predictors of
      contraceptive use. RESULTS: A total of 893,073 women were included, of whom
      130,080 were immigrants. More native women (38%) used hormonal contraceptives
      compared with all immigrant groups (15-24%). The odds ratios for any use of
      hormonal contraceptives for immigrants compared with Norwegian-born women were;
      Nordic countries 0.53, South and Central America 0.53, Western countries 0.39,
      Asia 0.30, Eastern Europe 0.29, Africa 0.29. Work, education, long stay in Norway
      and young age of immigration predicted the use of hormonal contraceptives among
      immigrants. CONCLUSIONS: The use of hormonal contraceptives varies between
      natives and immigrant groups. Further work is needed to ascertain whether these
      differences can be explained by higher desires for fertility, preferential use of
      non-hormonal contraceptives or other reasons identified through qualitative
      research.

PMID- 24931490
TI  - Subgroup analyses in cost-effectiveness analyses to support health technology
      assessments.
AB  - 'Success' in drug development is bringing to patients a new medicine that has an
      acceptable benefit-risk profile and that is also cost-effective. Cost
      effectiveness means that the incremental clinical benefit is deemed worth paying
      for by a healthcare system, and it has an important role in enabling
      manufacturers to obtain new medicines to patients as soon as possible following
      regulatory approval. Subgroup analyses are increasingly being utilised by
      decision-makers in the determination of the cost-effectiveness of new medicines
      when making recommendations. This paper highlights the statistical considerations
      when using subgroup analyses to support cost-effectiveness for a health
      technology assessment. The key principles recommended for subgroup analyses
      supporting clinical effectiveness published by Paget et al. are evaluated with
      respect to subgroup analyses supporting cost-effectiveness. A health technology
      assessment case study is included to highlight the importance of subgroup
      analyses when incorporated into cost-effectiveness analyses. In summary, we
      recommend planning subgroup analyses for cost-effectiveness analyses early in the
      drug development process and adhering to good statistical principles when using
      subgroup analyses in this context. In particular, we consider it important to
      provide transparency in how subgroups are defined, be able to demonstrate the
      robustness of the subgroup results and be able to quantify the uncertainty in the
      subgroup analyses of cost-effectiveness.

PMID- 24931491
TI  - Tapping the wisdom of the crowd: new initiatives are engaging the public as
      active participants in biomedical research.

PMID- 24931489
TI  - An iCRISPR platform for rapid, multiplexable, and inducible genome editing in
      human pluripotent stem cells.
AB  - Human pluripotent stem cells (hPSCs) offer a unique platform for elucidating the
      genes and molecular pathways that underlie complex traits and diseases. To
      realize this promise, methods for rapid and controllable genetic manipulations
      are urgently needed. By combining two newly developed gene-editing tools, the
      TALEN and CRISPR/Cas systems, we have developed a genome-engineering platform in
      hPSCs, which we named iCRISPR. iCRISPR enabled rapid and highly efficient
      generation of biallelic knockout hPSCs for loss-of-function studies, as well as
      homozygous knockin hPSCs with specific nucleotide alterations for precise
      modeling of disease conditions. We further demonstrate efficient one-step
      generation of double- and triple-gene knockout hPSC lines, as well as stage
      specific inducible gene knockout during hPSC differentiation. Thus the iCRISPR
      platform is uniquely suited for dissection of complex genetic interactions and
      pleiotropic gene functions in human disease studies and has the potential to
      support high-throughput genetic analysis in hPSCs.

PMID- 24931492
TI  - Label-free detection of folate receptor (+) cells by molecular recognition
      mediated electrochemiluminescence of CdTe nanoparticles.
AB  - Molecular recognition based rapid and simple techniques for identifying subtypes
      of cancer cells are essential in molecular medicine. In this work, we have
      designed a molecular recognition mediated electrochemiluminescent (ECL) strategy
      for label-free and sensitive detection of folate receptor (FR) (+) cells (HeLa
      cell as a model) on folic acid-functionalized and red emitting CdTe/GSH
      nanoparticle-modified indium-tin oxide (ITO) electrodes. The ECL emission
      selectively responses to the rapid binding of FR (+) cells on the modified ITO
      electrodes due to the block of electron exchange between CdTe nanoparticles and
      coreacted dissolved oxygen. Microscopic observation verifies that the binding of
      HeLa cells is more favored than that for HepG2 cells [FR (-) type], resulting in
      a great difference in ECL intensity. The proposed platform allows the detection
      of ~35 cells from 10 MUL of cell suspension. This study has laid the foundation
      for building rapid and low-cost ECL diagnostic devices for specific detection of
      FR (+) cancer cells, with potential applications in profiling of cancer cell
      subtypes.

PMID- 24931493
TI  - Screening of obstructive sleep apnea with empirical mode decomposition of pulse
      oximetry.
AB  - Detection of desaturations on the pulse oximetry signal is of great importance
      for the diagnosis of sleep apneas. Using the counting of desaturations, an index
      can be built to help in the diagnosis of severe cases of obstructive sleep apnea
      hypopnea syndrome. It is important to have automatic detection methods that
      allows the screening for this syndrome, reducing the need of the expensive
      polysomnography based studies. In this paper a novel recognition method based on
      the empirical mode decomposition of the pulse oximetry signal is proposed. The
      desaturations produce a very specific wave pattern that is extracted in the modes
      of the decomposition. Using this information, a detector based on properly
      selected thresholds and a set of simple rules is built. The oxygen desaturation
      index constructed from these detections produces a detector for obstructive sleep
      apnea-hypopnea syndrome with high sensitivity (0.838) and specificity (0.855) and
      yields better results than standard desaturation detection approaches.

PMID- 24931494
TI  - The cell composition of infused donor lymphocyte has different impact in
      different types of allogeneic hematopoietic stem cell transplantation.
AB  - Donor lymphocyte infusion (DLI) is often used to enhance the graft-versus
      leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT). In this study, we first evaluated the impact of the cell composition
      of a modified DLI (mDLI) on the prognoses of patients. A total of 194 patients
      undergoing allo-HSCT were enrolled and received mDLI for various clinical
      reasons. The infused cellular components of the mDLI were examined by flow
      cytometry. The results showed that infusion with a lower dose of CD14(+) cells
      (<0.33 * 10(8) /kg) was an independent risk factor for the occurrence of II-IV
      acute graft-versus-host disease (aGVHD) (HR = 0.104, p = 0.032) in human
      leukoctye antigen-identical transplant patients. In addition, a dose of CD14(+)
      cells greater than the 50th percentile was associated with a lower incidence of
      hematological relapse and longer disease-free survival (DFS) after the mDLI
      (relapse: HR = 0.193, p = 0.007; DFS: HR = 0.259, p = 0.016). However, we also
      found that a greater number of CD14(+) cells were an independent risk factor for
      II-IV aGVHD (HR = 1.758, p = 0.034) in haploidentical allo-HSCT. In conclusion,
      our data were the first to demonstrate that the cell composition of a 56 mDLI
      played a distinct role in different types of allo-HSCT. This finding provided a
      novel approach for the development of cellular therapies by manipulating the
      components of infused cells.

PMID- 24931496
TI  - Methods for identifying subject-specific abnormalities in neuroimaging data.
AB  - Algorithms that are capable of capturing subject-specific abnormalities (SSA) in
      neuroimaging data have long been an area of focus for diverse neuropsychiatric
      conditions such as multiple sclerosis, schizophrenia, and traumatic brain injury.
      Several algorithms have been proposed that define SSA in patients (i.e.,
      comparison group) relative to image intensity levels derived from healthy
      controls (HC) (i.e., reference group) based on extreme values. However, the
      assumptions underlying these approaches have not always been fully validated, and
      may be dependent on the statistical distributions of the transformed data. The
      current study evaluated variations of two commonly used techniques ("pothole"
      method and standardization with an independent reference group) for identifying
      SSA using simulated data (derived from normal, t and chi-square distributions)
      and fractional anisotropy maps derived from 50 HC. Results indicated substantial
      group-wise bias in the estimation of extreme data points using the pothole
      method, with the degree of bias being inversely related to sample size.
      Statistical theory was utilized to develop a distribution-corrected z-score
      (DisCo-Z) threshold, with additional simulations demonstrating elimination of the
      bias and a more consistent estimation of extremes based on expected
      distributional properties. Data from previously published studies examining SSA
      in mild traumatic brain injury were then re-analyzed using the DisCo-Z method,
      with results confirming the evidence of group-wise bias. We conclude that the
      benefits of identifying SSA in neuropsychiatric research are substantial, but
      that proposed SSA approaches require careful implementation under the different
      distributional properties that characterize neuroimaging data.

PMID- 24931497
TI  - Evolution of divergent female mating preference in response to experimental
      sexual selection.
AB  - Sexual selection is predicted to drive the coevolution of mating signals and
      preferences (mating traits) within populations, and could play a role in
      speciation if sexual isolation arises due to mating trait divergence between
      populations. However, few studies have demonstrated that differences in mating
      traits between populations result from sexual selection alone. Experimental
      evolution is a promising approach to directly examine the action of sexual
      selection on mating trait divergence among populations. We manipulated the
      opportunity for sexual selection (low vs. high) in populations of Drosophila
      pseudoobscura. Previous studies on these experimental populations have shown that
      sexual selection manipulation resulted in the divergence between sexual selection
      treatments of several courtship song parameters, including interpulse interval
      (IPI) which markedly influences male mating success. Here, we measure female
      preference for IPI using a playback design to test for preference divergence
      between the sexual selection treatments after 130 generations of experimental
      sexual selection. The results suggest that female preference has coevolved with
      male signal, in opposite directions between the sexual selection treatments,
      providing direct evidence of the ability of sexual selection to drive the
      divergent coevolution of mating traits between populations. We discuss the
      implications in the context sexual selection and speciation.

PMID- 24931498
TI  - Expression, purification and characterization of soluble recombinant peptidyl
      prolyl cis/trans isomerase from Vibrio anguillarum.
AB  - Vibrio anguillarum, a causative agent of vibriosis in finfish, crustaceans, and
      bivalves, is a Gram-negative, motile marine bacterium. Most bacteria have
      developed survival strategies in various environments. The aim of this study was
      to investigate the changes in protein expression of V. anguillarum O1 incubated
      under different conditions using two dimensional electrophoresis and MALDI-TOF
      MS/MS analysis. Result indicated that peptidyl-prolyl cis/trans isomerase
      (PPIase) expression was increasingly appeared when incubated at low temperature
      (15 degrees C) and alkaline conditions (pH 10). Subsequently, the ppi gene from
      V. anguillarum O1 was isolated and overexpressed in Escherichia coli to
      characterize the biochemical properties. The cloned ppi gene encoded 206 amino
      acids containing the conserved regions identified in FK506 binding pocket. To
      determine the optimal conditions of the purified recombinant PPIase protein
      (VaFKBP22), we used Succinyl-Ala-Phe-Pro-Phe-p nitroanilide as substrate and the
      highest enzymatic activity was found at 5 degrees C and pH 6. VaFKBP22 was
      detected in the cytoplasm and periplasm of V. anguillarum O1. In addition,
      VaFKBP22 also showed chaperone activity and did not show cytotoxic activity.

PMID- 24931499
TI  - Inducing the oxidative stress response in Escherichia coli improves the quality
      of a recombinant protein: magnesium chelatase ChlH.
AB  - The ~150kDa ChlH subunit of magnesium chelatase from Oryza sativa, Hordeum
      vulgare and Chlamydomonas reinhardtii have been heterologously expressed in
      Escherichiacoli. The active soluble protein is found as both a multimeric and a
      monomeric form. The multimeric ChlH appears to be oxidatively damaged but monomer
      production is favoured in growth conditions that are known to cause an oxidative
      stress response in E.coli. Inducing an oxidative stress response may be of
      general utility to improve the quality of proteins expressed in E. coli. The
      similar responses of ChlH's from the three different species suggest that
      oligomerization of oxidatively damaged ChlH may have a functional role in the
      chloroplast, possibly as a signal of oxidative stress or damage.

PMID- 24931500
TI  - Purification and identification of a novel antifungal protein secreted by
      Penicillium citrinum from the Southwest Indian Ocean.
AB  - A novel antifungal protein produced by the fungal strain Penicillium citrinum W1,
      which was isolated from a Southwest Indian Ocean sediment sample, was purified
      and characterized. The culture supernatant of P. citrinum W1 inhibited the
      mycelial growth of some plant pathogenic fungi. After saturation of P. citrinum
      W1 culture supernatants with ammonium sulfate and ion-exchange chromatography, an
      antifungal protein (PcPAF) was purified. The N-terminal amino acid sequence
      analysis showed that PcPAF might be an unknown antifungal protein. PcPAF
      displayed antifungal activity against Trichoderma viride, Fusarium oxysporum,
      Paecilomyces variotii, and Alternaria longipes at minimum inhibitory
      concentrations of 1.52, 6.08, 3.04, and 6.08 ug/disc, respectively. PcPAF
      possessed high thermostability and had a certain extent of protease and metal ion
      resistance. The results suggested that PcPAF may represent a novel antifungal
      protein with potential application in controlling plant pathogenic fungal
      infection.

PMID- 24931501
TI  - GST2 is required for nitrogen starvation-induced filamentous growth in Candida
      albicans.
AB  - Candida albicans, the major human fungal pathogen, undergoes morphological
      transition from the budding yeast form to filamentous growth in response to
      nitrogen starvation. In this study, we identified a new function of GST2, whose
      expression was required for filamentous growth of C. albicans under nitrogen
      limiting conditions. The DeltaGst2p showed Gst activity and required response to
      oxidative stress. The Deltagst2 mutant displayed predominantly yeast phase growth
      in low ammonium media. Such morphological defect of Deltagst2 mutants was not
      rescued by overexpression of Mep2p, Cph1p, or Efg1p, but was rescued by either
      overexpression of a hyperactive RAS1(G13V) allele or through exogenous addition
      of cyclic AMP. In addition, the Deltagst2 mutants had lower levels of RAS1
      transcripts than wild-type cells under conditions of nitrogen starvation. These
      results were consistent with the Ras1-cAMP pathway as a possible downstream
      target of Gst2p. These findings suggest that Gst2p is a significant component of
      nitrogen starvation-induced filamentation in C. albicans. 

PMID- 24931502
TI  - Functional characterization of 5-enopyruvylshikimate-3-phosphate synthase from
      Alkaliphilus metalliredigens in transgenic Arabidopsis.
AB  - Although a large number of AroA enzymes (EPSPS: 5-enopyruvylshikimate-3-phosphate
      synthase) have been identified, cloned, and tested for glyphosate resistance,
      only two AroA variants, derived from Agrobacterium tumefaciens strain CP4 and Zea
      mays, have been utilized to produce the commercial glyphosate-resistant crops.
      Here, we have used a PCR-based twostep DNA synthesis method to synthesize an aroA
      gene (aroAA. metalliredigens) from Alkaliphilus metalliredigens, encoding a new
      EPSPS. Furthermore, transgenic Arabidopsis with the new aroAA. metalliredigens
      gene was obtained to confirm the potential of the novel aroA gene in developing
      glyphosate-resistant crops.

PMID- 24931503
TI  - Development of novel microsatellite markers for strain-specific identification of
      Chlorella vulgaris.
AB  - A strain-specific identification method is required to secure Chlorella strains
      with useful genetic traits, such as a fast growth rate or high lipid
      productivity, for application in biofuels, functional foods, and pharmaceuticals.
      Microsatellite markers based on simple sequence repeats can be a useful tool for
      this purpose. Therefore, this study developed five novel microsatellite markers
      (mChl-001, mChl-002, mChl-005, mChl-011, and mChl-012) using specific loci along
      the chloroplast genome of Chlorella vulgaris. The microsatellite markers were
      characterized based on their allelic diversities among nine strains of C.
      vulgaris with the same 18S rRNA sequence similarity. Each microsatellite marker
      exhibited 2~5 polymorphic allele types, and their combinations allowed
      discrimination between seven of the C. vulgaris strains. The two remaining
      strains were distinguished using one specific interspace region between the mChl
      001 and mChl-005 loci, which was composed of about 27 single nucleotide
      polymorphisms, 13~15 specific sequence sites, and (T)n repeat sites. Thus, the
      polymorphic combination of the five microsatellite markers and one specific locus
      facilitated a clear distinction of C. vulgaris at the strain level, suggesting
      that the proposed microsatellite marker system can be useful for the accurate
      identification and classification of C. vulgaris. 

PMID- 24931504
TI  - Protein-poly(amino acid) complex precipitation for high-concentration protein
      formulation.
AB  - A method for concentration of protein solutions is required for high-dosage
      protein formulation. Here, we present a precipitation-redissolution method by
      poly(amino acid) for proteins, including therapeutic enzymes, antibodies, and
      hormones. The proteins were fully precipitated by the addition of poly-L-lysine
      or poly-L-glutamic acid at low ionic strength, after which precipitate was
      dissolved at physiological ionic strength. The activities and secondary
      structures of redissolved proteins, especially antibodies, were almost identical
      to the native state. The precipitation-redissolution method is a simple and rapid
      technique for concentration of protein formulations.

PMID- 24931505
TI  - Metallic resist for phase-change lithography.
AB  - Currently, the most widely used photoresists in optical lithography are organic
      based resists. The major limitations of such resists include the photon
      accumulation severely affects the quality of photolithography patterns and the
      size of the pattern is constrained by the diffraction limit. Phase-change
      lithography, which uses semiconductor-based resists such as chalcogenide
      Ge2Sb2Te5 films, was developed to overcome these limitations. Here, instead of
      chalcogenide, we propose a metallic resist composed of Mg58Cu29Y13 alloy films,
      which exhibits a considerable difference in etching rate between amorphous and
      crystalline states. Furthermore, the heat distribution in Mg58Cu29Y13 thin film
      is better and can be more easily controlled than that in Ge2Sb2Te5 during
      exposure. We succeeded in fabricating both continuous and discrete patterns on
      Mg58Cu29Y13 thin films via laser irradiation and wet etching. Our results
      demonstrate that a metallic resist of Mg58Cu29Y13 is suitable for phase change
      lithography, and this type of resist has potential due to its outstanding
      characteristics.

PMID- 24931506
TI  - Detection of Candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy
      samples.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between
      expression of Candida albicans alcohol dehydrogenases (ADH) genes in archival
      formalin-fixed paraffin-embedded (FFPE) samples from biopsies of leukoplakia.
      MATERIALS AND METHODS: Archival FFPE samples were obtained from four sample
      groups: normal oral mucosa, non-dysplastic leukoplakia, chronic hyperplastic
      candidosis (CHC), and non-CHC dysplastic leukoplakia. The presence of C. albicans
      was determined by periodic acid Schiff staining and by immunocytochemistry. C.
      albicans ADH1 and ADH2 mRNAs were detected using reverse transcription PCR.
      RESULTS: Candida albicans was detected in FFPE samples diagnosed as CHC (the
      histological diagnoses had been made by specialist oral pathologists, using
      uniform criteria), but not in any other sample group, including the non
      dysplastic leukoplakias. RT-PCR confirmed a significant correlation between the
      expression of CaADH1 mRNA (P = 0.000), but not for CaADH2 mRNA (P = 0.056) in
      archival FFPE samples (n = 31) from biopsies of leukoplakia. CONCLUSIONS: Candida
      albicans was the predominant species in the lesions diagnosed as CHC, and the
      presence of C. albicans in CHC lesions was associated with a high expression of
      C. albicans ADH1 mRNA. There was no association between the presence of Candida
      and malignant transformation in the cases examined; however, the number of cases
      was limited and further studies are needed to further elucidate the role of C.
      albicans ADH1 in the pathogenesis of oral squamous cell carcinoma.

PMID- 24931507
TI  - Japan Clinical Oncology Group (JCOG) prognostic index and characterization of
      long-term survivors of aggressive adult T-cell leukaemia-lymphoma (JCOG0902A).
AB  - This study evaluated the clinical features of 276 patients with aggressive adult
      T-cell leukaemia-lymphoma (ATL) in 3 Japan Clinical Oncology Group (JCOG) trials.
      We assessed the long-term survivors who survived >5 years and constructed a
      prognostic index (PI), named the JCOG-PI, based on covariates obtained by Cox
      regression analysis. The median survival time (MST) of the entire cohort was 11
      months. In 37 patients who survived >5 years, no disease-related deaths in 10
      patients with lymphoma-type were observed in contrast to the 10 ATL-related
      deaths in other types. In multivariate analysis of 193 patients, the JCOG-PI
      based on corrected calcium levels and performance status identified moderate and
      high risk groups with an MST of 14 and 8 months respectively (hazard ratio,
      1.926). The JCOG-PI was reproducible in an external validation. Patients with
      lymphoma-type who survived >5 years might have been cured. The JCOG-PI is
      valuable for identifying patients with extremely poor prognosis and will be
      useful for the design of future trials combining new drugs or investigational
      treatment strategies.

PMID- 24931508
TI  - Quantitative measurement and mechanisms for CH4 production from hydrates with the
      injection of liquid CO2.
AB  - The recovery of gas from natural gas hydrates under the permafrost and in oceanic
      sediments is of particular interest in energy and environmental fields because of
      the attractive process to release methane gas through the injection of CO2. The
      sequestration of CO2, a notorious greenhouse gas, in hydrates has the potential
      to be used in enhanced gas recovery techniques, while simultaneously releasing
      CH4 locked within the gas bearing hydrates. In this study, we present
      quantitative experiments to investigate results of possible CH4-CO2 exchange
      kinetics from injection of liquid CO2 through CH4 hydrates. The experiments
      performed use CH4 hydrate formed from ice particles (75-90 or 125-150 microns in
      diameter) at approximately 10.34 MPa and 263 K. In order to reduce unexpected
      errors, nearly full conversion (>95%) of ice particles to hydrates is achieved.
      Liquid CO2 is injected into the pressure cell to sweep the residual CH4
      atmosphere, ensuring no free CH4 is left in the gas phase. After soaking the
      hydrate for several hours, CH4 is produced from the hydrates by injecting liquid
      CO2. The final composition and analysis of the produced CH4 is measured by using
      in-line gas chromatography. We also measure the CH4 moles after hydrate
      dissociation to confirm the closure of the total mass balance of the experiment.
      From these data, we infer the mechanism for CH4 production, identify the
      penetration depth of the dissociation/exchange on the hydrate particles, and
      propose physical models describing the mechanism for CH4 production. These
      experiments are essential in the quantification of the production of CH4 from CH4
      hydrates with the injection of CO2. 

PMID- 24931509
TI  - Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain.

PMID- 24931510
TI  - Enantiospecific analysis of 8-prenylnaringenin in biological fluids by liquid
      chromatography-electrospray ionization mass spectrometry: application to
      preclinical pharmacokinetic investigations.
AB  - 8-Prenylnaringenin (8PN) is a naturally occurring bioactive chiral
      prenylflavonoid found most commonly in the female flowers of hops (Humulus
      lupulus L.). A stereospecific method of analysis for 8PN in biological fluids is
      necessary to study the pharmacokinetic disposition of each enantiomer. A novel
      and simple liquid chromatographic-electrospray ionization-mass spectrometry (LC
      ESI-MS) method was developed for the simultaneous determination of R- and S-8PN
      in rat serum and urine. Carbamazepine was used as the internal standard (IS).
      Enantiomeric resolution of 8PN was achieved on a Chiralpak((r)) AD-RH column with
      an isocratic mobile phase consisting of 2-propanol and 10 mM ammonium formate (pH
      8.5) (40:60, v/v) and a flow rate of 0.7 mL/min. Detection was achieved using
      negative selective ion monitoring (SIM) of 8PN at m/z 339.15 for both enantiomers
      and positive SIM m/z at 237.15 for the IS. The calibration curves for urine were
      linear over a range of 0.01-75 ug/mL and 0.05-75 ug/mL for serum with a limit of
      quantification of 0.05 ug/mL in serum and 0.01 ug/mL in urine. The method was
      successfully validated showing that it was sensitive, reproducible, and accurate
      for enantiospecific quantification of 8PN in biological matrices. The assay was
      successfully applied to a preliminary study of 8PN enantiomers in rat.

PMID- 24931512
TI  - Comparative phenotypic and genotypic analyses of Salmonella Rissen that
      originated from food animals in Thailand and United States.
AB  - Salmonella enterica serovar Rissen has been recognized as one of the most common
      serovar among humans and pork production systems in different parts of the world,
      especially Asia. In the United States, this serovar caused outbreaks but its
      epidemiologic significance remains unknown. The objectives of this study were to
      compare the phenotypic (antimicrobial susceptibility) and genotypic attributes of
      Salmonella Rissen isolated in Thailand (Thai) and the United States (US). All the
      Thai isolates (n = 30) were recovered from swine faecal samples. The US isolates
      (n = 35) were recovered from swine faecal samples (n = 29), cattle (n = 2),
      chicken (n = 2), dog (n = 1) and a ready-to-eat product (n = 1). The
      antimicrobial susceptibility of isolates was determined using the Kirby-Bauer
      disk diffusion method with a panel of 12 antimicrobials. Pulse-field gel
      electrophoresis (PFGE) was used to determine the genotypic diversity of isolates.
      All Thai isolates showed multidrug resistance (MDR) with the most frequent
      antibiotic resistance shown against ampicillin (100%), sulfisoxazole (96.7%),
      tetracycline (93.3%), streptomycin (90%) and chloramphenicol (30%). About half of
      the isolates of USA origin were pan-susceptible and roughly 30% were resistant to
      only tetracycline (R-type: Te). Salmonella Rissen isolated from Thailand and the
      USA in this study were found to be clonally unrelated. Genotypic analyses
      indicated that isolates were clustered primarily based on the geographic origin
      implying the limited clonality among the strains. Clonal relatedness among
      different host species within the same geography (USA) was found. We found
      genotypic similarity in Thai and US isolates in few instances but with no
      epidemiological link. Further studies to assess propensity for increased inter
      regional transmission and dissemination is warranted.

PMID- 24931511
TI  - Ischaemic cardiovascular risk and prescription of non-steroidal anti-inflammatory
      drugs for musculoskeletal complaints.
AB  - OBJECTIVE: To determine the influence of ischaemic cardiovascular (CV) risk on
      prescription of non-steroidal anti-inflammatory drugs (NSAIDs) by general
      practitioners (GPs) in patients with musculoskeletal complaints. DESIGN: Cohort
      study. SETTING: A healthcare database containing the electronic GP medical
      records of over one million patients throughout the Netherlands. PATIENTS: A
      total of 474 201 adults consulting their GP with a new musculoskeletal complaint
      between 2000 and 2010. Patients were considered at high CV risk if they had a
      history of myocardial infarction, angina pectoris, stroke, transient ischaemic
      attack, or peripheral arterial disease, and at low CV risk if they had no CV risk
      factors. MAIN OUTCOME MEASURES: Frequency of prescription of non-selective
      (ns)NSAIDs and selective cyclooxygenase-2 inhibitors (coxibs). RESULTS: Overall,
      24.4% of patients were prescribed an nsNSAID and 1.4% a coxib. Of the 41,483
      patients with a high CV risk, 19.9% received an nsNSAID and 2.2% a coxib. These
      patients were more likely to be prescribed a coxib than patients with a low CV
      risk (OR 1.9, 95% CI 1.8-2.0). Prescription of nsNSAIDs decreased over time in
      all risk groups and was lower in patients with a high CV risk than in patients
      with a low CV risk (OR 0.8, 95% CI 0.7-0.8). CONCLUSION: Overall, patients with a
      high CV risk were less likely to be prescribed an NSAID for musculoskeletal
      complaints than patients with a low CV risk. Nevertheless, one in five high CV
      risk patients received an NSAID, indicating that there is still room for
      improvement.

PMID- 24931514
TI  - Do homoarginine and asymmetric dimethylarginine act antagonistically in the
      cardiovascular system?

PMID- 24931513
TI  - Polo-like kinase 1 regulates the stability of the mitotic centromere-associated
      kinesin in mitosis.
AB  - Proper bi-orientation of chromosomes is critical for the accurate segregation of
      chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic
      centromere-associated kinesin. During mitosis the activity and localization of
      MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show
      here that S621 in the MCAK's C-terminal domain is the major phosphorylation site
      for Plk1. This phosphorylation regulates MCAK's stability and facilitates its
      recognition by the ubiquitin/proteasome dependent APC/C(Cdc20) pathway leading to
      its D-box dependent degradation in mitosis. While phosphorylation of S621 does
      not directly affect its microtubule depolymerising activity, loss of Plk1
      phosphorylation on S621 indirectly enhances its depolymerization activity in vivo
      by stabilizing MCAK, leading to an increased level of protein. Interfering with
      phosphorylation at S621 causes spindle formation defects and chromosome
      misalignments. Therefore, this study suggests a new mechanism by which Plk1
      regulates MCAK: by regulating its degradation and hence controlling its turnover
      in mitosis.

PMID- 24931515
TI  - Do homoarginine and asymmetric dimethylarginine act antagonistically in the
      cardiovascular system?

PMID- 24931516
TI  - Assessment of plaque composition by intravascular ultrasound and near-infrared
      spectroscopy: from PROSPECT I to PROSPECT II.
AB  - Atherosclerosis is the main cause of coronary artery disease (CAD), which is
      today the leading cause of death worldwide and will continue to be the first in
      the world in 2030. Vulnerable coronary plaques are usually characterized by a
      high content of necrotic core, a thin inflamed fibrous cap (intense accumulation
      of macrophages) and scarce presence of smooth muscle cells. None of these
      characteristics can be estimated by coronary angiography, which on the contrary
      underestimates the magnitude of atherosclerotic burden, particularly in earlier
      stage disease when positive vascular remodeling may allow "normal" lumen caliber
      despite substantial vascular wall plaque. The recognition of the ubiquity of
      substantial but non-flow limiting lesions that may be at high risk for subsequent
      plaque rupture has resulted in a paradigm shift in thinking about the
      pathophysiology of CAD, with the focus no longer solely on the degree of arterial
      luminal narrowing. This growing need for more information about coronary
      atherosclerosis in order to identify patients and lesions at risk for
      complications during PCI and for future adverse cardiac events has been the
      primary impetus for the development of novel intracoronary imaging methods able
      to detect plaque composition, in particular presence of a necrotic core/lipid
      pool, such as intravascular ultrasound virtual histology and near-infrared
      spectroscopy. These imaging technologies and their clinical and clinical/research
      applications are discussed in detail.

PMID- 24931517
TI  - Mortality and survival in systemic sclerosis: systematic review and meta
      analysis.
AB  - OBJECTIVE: To determine the mortality, survival, and causes of death in patients
      with systemic sclerosis (SSc) through a meta-analysis of the observational
      studies published up to 2013. METHODS: We performed a systematic review and meta
      analysis of the observational studies in patients with SSc and mortality data
      from entire cohorts published in MEDLINE and SCOPUS up to July 2013. RESULTS: A
      total of 17 studies were included in the mortality meta-analysis from 1964 to
      2005 (mid-cohort years), with data from 9239 patients. The overall SMR was 2.72
      (95% CI: 1.93-3.83). A total of 43 studies have been included in the survival
      meta-analysis, reporting data from 13,529 patients. Cumulative survival from
      onset (first Raynaud's symptom) has been estimated at 87.6% at 5 years and 74.2%
      at 10 years, from onset (non-Raynaud's first symptom) 84.1% at 5 years and 75.5%
      at 10 years, and from diagnosis 74.9% at 5 years and 62.5% at 10 years. Pulmonary
      involvement represented the main cause of death. CONCLUSIONS: SSc presents a
      larger mortality than general population (SMR = 2.72). Cumulative survival from
      diagnosis has been estimated at 74.9% at 5 years and 62.5% at 10 years. Pulmonary
      involvement represented the main cause of death.

PMID- 24931519
TI  - Effect of HIF1alpha on Foxp3 expression in CD4+ CD25- T lymphocytes.
AB  - The aim of the present study was to investigate the effect of HIF1alpha on Foxp3
      expression in CD4(+) CD25(-) T lymphocytes. CD4(+) CD25(-) T lymphocytes were
      sorted from PBMC using a CD4(+) CD25(+) regulatory T cell isolation kit.
      Lentivirus containing lentiviral vector that overexpressed HIF1alpha (HIF-lenti)
      and those containing empty expression vector (control-lenti) were produced.
      Meanwhile, lentivirus that contained lentiviral vector that suppressed HIF1alpha
      expression (siHIF-lenti) and those containing control vector (sicontrol-lenti)
      were also generated. The sorted CD4(+) CD25(-) T lymphocytes were infected with
      HIF-lenti, control-lenti, siHIF-lenti, and sicontrol-lenti, respectively.
      Approximately 72 hr after transduction, real-time PCR and Western blot were
      carried out to analyze the RNA and protein expression level of HIF1alpha and
      Foxp3. CD4(+) CD25(-) T lymphocytes cultured under 21% O2 , 5% CO2 (normoxia) and
      1% O2 , 5% CO2 (hypoxia) were used as control. Our results showed that
      overexpression of HIF1alpha increased both mRNA and protein expression of Foxp3
      and, meanwhile, suppression of HIF1alpha expression by RNAi could reverse high
      Foxp3 expression in CD4(+) CD25(-) T lymphocytes caused by hypoxic culture. These
      results suggested that hypoxia could stimulate Foxp3 expression by increasing
      HIF1alpha expression in CD4(+) T lymphocytes which may promote CD4(+) T
      lymphocytes to convert to Treg.

PMID- 24931518
TI  - The role of additional radiotherapy for primary central nervous system lymphoma.
AB  - BACKGROUND: Prior to the introduction of the chemotherapeutic agent methotrexate,
      radiotherapy was the sole, first-line option for the treatment of individuals
      with primary central nervous system lymphoma (PCNSL), Now that methotrexate is
      available, the role of radiotherapy in the treatment of PCNSL has been called
      into question. Although various studies suggest promising results with regard to
      overall and progression-free survival with the use of chemotherapeutic regimens
      alone as well as in combination with radiotherapy, no evidence-based standard
      regimen has yet been defined. OBJECTIVES: The objective of this review was to
      assess and summarise the evidence available regarding the efficacy and
      tolerability of radiotherapy in addition to chemotherapy in the treatment of
      immunocompetent individuals with PCNSL. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (issue 01.2014), MEDLINE from
      January 1950 to February 2014 and conference proceedings from 2005 to 2013. 
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing
      chemotherapy plus radiotherapy with chemotherapy alone in individuals with PCNSL.
      Outcomes defined in this review were overall survival, progression-free survival,
      response to treatment, adverse events, treatment related mortality and quality of
      life. We excluded trials in which the chemotherapy regimen differed between
      treatment arms, trials in which fewer than 80% of participants had PCNSL or those
      recruiting immunocompromised individuals with PCNSL. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened the results of the search
      strategies for eligibility for this review. Both assessed risk of bias. Where
      relevant data was unavailable, we contacted the investigator by email. MAIN
      RESULTS: Of the 556 potentially relevant studies only two met the inclusion
      criteria. One of those was excluded as the trial was abandoned prematurely and
      reported only preliminary results. The only analysed trial enrolled 551
      participants receiving first-line chemotherapy (methotrexate) followed by whole
      brain radiotherapy (WBR) or receiving chemotherapy only (methotrexate followed by
      cytarabine in case of incomplete response). In this non-inferiority trial, the
      intention-to-treat (ITT) population consisted of 411 participants and the per
      protocol (PP) population of 318 participants. We judged the potential for risk of
      bias in this open-label study as moderate.The estimated effect of chemotherapy
      plus WBR on survival was similar to that with chemotherapy alone but due to a
      wide CI we could not rule out the superiority of either therapy. This applied to
      both the ITT population (HR 1.01, 95% CI 0.79 to 1.30; P = 0.94) and the PP
      population (HR 1.06, 95% CI 0.80 to 1.40; P = 0.71) (moderate-quality evidence).
      Due to the low number of participants and a risk of detection bias we found low
      quality evidence for an improvement in progression-free survival in participants
      in the ITT population receiving WBR in addition to chemotherapy (HR 0.79, 95% CI
      0.63 to 0.99; P = 0.041). An improvement in PFS was also observed with WBR plus
      chemotherapy in participants in the PP population, but the CI was slightly wider
      and the result not significant (HR 0.82,95% CI 0.64 to 1.07; P = 0.14). Treatment
      related mortality and health-related quality of life were not evaluated.
      Treatment-related neurotoxicity was assessed clinically in 79 participants,
      revealing signs of neurotoxicity in 49% of those receiving chemotherapy plus
      radiotherapy and in 26% of those receiving chemotherapy only (RR 1.85, 95% CI
      0.98 to 3.48; P = 0.054) (very-low-quality evidence). AUTHORS' CONCLUSIONS: In
      summary, the currently available evidence (one RCT) is not sufficient to conclude
      that WBR plus chemotherapy and chemotherapy alone have similar effects on overall
      survival in people with PCNSL. The findings suggest that the addition of
      radiotherapy (WBR) to chemotherapy may increase progression-free survival, but
      may also increase the incidence of neurotoxicity compared to chemotherapy only
      (methotrexate monotherapy). As the role of chemoradiotherapy in the treatment of
      PCNSL remains unclear, further prospective, randomised trials are needed before
      definitive conclusions can be drawn.

PMID- 24931520
TI  - Effects of feeding lauric acid or coconut oil on ruminal protozoa numbers,
      fermentation pattern, digestion, omasal nutrient flow, and milk production in
      dairy cows.
AB  - The objectives of this study were to evaluate the feeding of coconut oil (CO), in
      which lauric acid (La) comprises about 50% of the fatty acid composition, as a
      practical rumen protozoa (RP) suppressing agent, to assess whether the source of
      La affects ruminal fermentation and animal performance and to test whether
      suppressing RP improves N utilization, nutrient digestion, nutrient flow at the
      omasal canal, and milk production. Fifteen multiparous Holstein cows (3 fitted
      with ruminal cannulas) and 15 primiparous Holstein cows (3 fitted with ruminal
      cannulas) were used in a replicated 3*3 Latin square experiment with 14d of
      adaptation and 14d of sample collection. Diets were fed as total mixed ration and
      contained (dry matter basis) 10% corn silage, 50% alfalfa silage, and 40%
      concentrate. The control diet contained 3% (dry matter basis) calcium soaps of
      palm oil fatty acids (Megalac, Church & Dwight Co. Inc., Princeton, NJ) as a
      ruminally inert fat source and had no added La or CO. Diets with La and CO were
      formulated to contain equal amounts of La (1.3%, dry matter basis). Dry matter
      intake was not affected by treatment. Both CO and La reduced RP numbers by about
      40%. Lauric acid reduced yield of milk and milk components; however, CO did not
      affect yield of milk and yields of milk components. Both La and CO caused small
      reductions in total VFA concentration; CO increased molar proportion of ruminal
      propionate, reduced ruminal ammonia and branched-chain volatile fatty acids,
      suggesting reduced protein degradation, and reduced milk urea N and blood urea N
      concentrations, suggesting improved protein efficiency. Lauric acid reduced total
      tract apparent digestibility of neutral detergent fiber and acid detergent fiber
      as well as ruminal apparent digestibility of neutral detergent fiber and acid
      detergent fiber as measured at the omasal canal; however, CO did not alter fiber
      digestion. Microbial protein flow at the omasal canal, as well as the flow of N
      fractions at the omasal canal, did not differ among treatments. Results from this
      experiment have confirmed that dietary La is not a practical agent for
      suppressing RP population in dairy cows, mainly because of its negative effects
      on fiber digestion and ruminal fermentation. Intake of CO appeared to reduce
      ruminal and improve protein efficiency, but did not improve milk production, milk
      composition, or increase microbial outflow from the rumen. Based on the results
      of this study, a 40% reduction of RP population is not sufficient to improve N
      utilization in dairy cows. 

PMID- 24931521
TI  - Hepatic patatin-like phospholipase domain-containing protein 3 sequence, single
      nucleotide polymorphism presence, protein confirmation, and responsiveness to
      energy balance in dairy cows.
AB  - Patatin-like phospholipase domain-containing protein 3 (PNPLA3), commonly known
      as adiponutrin, is part of a novel subfamily of triglyceride lipase enzymes with
      potential effects on triglyceride metabolism in adipose and hepatic tissues. The
      predicted bovine PNPLA3 sequence has been identified, but expression of the gene
      had not been examined. The objectives of this study were to confirm the predicted
      bovine PNPLA3 gene sequence, determine expression of the bovine PNPLA3 gene in
      response to whole-animal energy balance, identify single nucleotide polymorphisms
      present in dairy cows, and verify the presence of the protein in the liver. Using
      liver biopsy samples collected from cows at +28d relative to calving (DRTC), RNA
      was isolated and used to generate a cDNA template for amplification of the entire
      predicted coding sequence of PNPLA3 via PCR. To determine if energy balance
      alters the expression of PNPLA3, RNA was isolated and mRNA expression quantified
      in liver samples from mid-lactation cows after a 5-d ad libitum period (n=5) and
      after a subsequent 5-d 50% feed restriction period (n=5), and in samples
      collected from cows at -14, +1, +14, and +28 DRTC (n=16). The presence of PNPLA3
      protein was detected by Western blot in liver protein samples collected at +28
      DRTC. Expression of hepatic PNPLA3 was decreased after a period of feed
      restriction (8.14 vs. 1.08+/-2.17 arbitrary units, ad libitum vs. fasted).
      Expression of PNPLA3 mRNA was decreased at +1 and +14 DRTC compared with -14 DRTC
      (23.35, 7.28, 10.17, and 14.5+/-4.9 arbitrary units, -14, +1, +14, and +28 DRTC,
      respectively). The presence of PNPLA3 protein was detected as a 55-kDa band in
      hepatic protein isolations from liver tissue collected at +28 DRTC. These data
      confirm the presence and sequence of the bovine hepatic PNPLA3 gene and single
      nucleotide polymorphisms. Furthermore, these data indicate responsiveness of
      bovine hepatic PNPLA3 to energy balance. 

PMID- 24931523
TI  - Free and immobilized Lactobacillus casei ATCC 393 on whey protein as starter
      cultures for probiotic Feta-type cheese production.
AB  - The use of free and immobilized Lactobacillus casei ATCC 393 on whey protein as
      starter culture in probiotic Feta-type cheese production was evaluated. The
      probiotic cultures resulted in significantly higher acidity; lower pH; reduced
      counts of coliforms, enterobacteria, and staphylococci; and improved quality
      characteristics compared with cheese with no culture. Microbiological and strain
      specific multiplex PCR analysis showed that both free and immobilized L. casei
      ATCC 393 were detected in the novel products at levels required for conferring a
      probiotic effect at the end of the ripening. The effect of starter culture on
      production of volatile compounds was investigated by the solid-phase
      microextraction gas chromatography-mass spectrometry analysis technique. The
      immobilized cells resulted in an improved profile of aroma-related compounds and
      the overall high quality of the novel products was ascertained by the preliminary
      sensory test. Finally, the high added value produced by exploitation of whey,
      which is an extremely polluting industrial waste, was highlighted and assessed. 

PMID- 24931522
TI  - Immune response against Treponema spp. and ELISA detection of digital dermatitis.
AB  - The objective of this longitudinal study was to evaluate the immune response
      against Treponema spp. infection in dairy heifers affected with digital
      dermatitis (DD). In addition, the accuracy of an indirect ELISA detecting anti
      Treponema IgG antibodies in identifying clinical DD status has been assessed. A
      cohort of 688 pregnant Holstein heifers was evaluated at least 3 times before
      calving during a period of 6 mo. Complete clinical assessment of DD presence on
      the back feet of each heifer and blood extraction were performed in a stand-up
      chute. Digital dermatitis cases were characterized by the M-stage classification
      system and size and level of skin proliferation. An ELISA was performed on blood
      serum samples obtained from a subcohort of 130 heifers. For description purposes,
      the animals were classified by the number of clinical cases experienced during
      the study period as type I (no clinical cases were observed), type II (only 1
      acute clinical case diagnosed), and type III (at least 2 acute clinical cases
      diagnosed). Multivariable repeated-measures models were used to evaluate the
      immune response against Treponema spp. infection. A binormal Bayesian model for
      the ELISA data without cut-point values was used to assess the accuracy of the
      ELISA as a diagnostic tool. Animals that never experienced a DD event throughout
      the study kept a constant low level of antibody titer. A 56% increase in mean
      ELISA titer was observed in heifers upon a first clinical DD case diagnosis.
      After topical treatment of an acute DD case with oxytetracycline, the antibody
      titer decreased progressively in type II heifers, achieving mean levels of those
      observed in healthy cows after a mean of 223 d. Surprisingly, antibody titer was
      not increased in the presence of M1 (DD lesion <20mm in diameter surrounded by
      healthy skin) and M4.1 (DD lesion <20mm in diameter embedded in a circumscribed
      dyskeratotic or proliferative skin alteration) DD stages. Type III cows showed a
      slight increase in antibody levels. The presence of skin proliferation at first
      DD diagnosis was found to be associated with an odds ratio of 2.04 of becoming a
      type III heifer in relation to heifers presenting first lesions without skin
      proliferation. The ELISA validity was estimated by an area under the curve of
      0.88. Predicted probabilities of infection are provided for a range of ELISA
      values and prevalence of infection. Early detection and treatment is essential to
      control DD and the ELISA can be used in understanding the immunopathology of DD
      and shows great promise for prescreening purposes during DD management programs
      in combination with traditional clinical inspection. 

PMID- 24931524
TI  - Association of coagulase-negative staphylococcal species, mammary quarter milk
      somatic cell count, and persistence of intramammary infection in dairy cattle.
AB  - This study was conducted to evaluate the association between subclinical
      intramammary infection (IMI) with coagulase-negative staphylococci (CNS), mammary
      quarter milk somatic cell count (SCC), and persistence of IMI in dairy cattle.
      Convenience samples of CNS isolates harvested from milk samples of subclinically
      infected mammary quarters collected between 4 and 2wk before drying-off, between
      2wk before drying-off and the day of drying-off, within 24h after calving,
      between 1 and 2wk after calving, and during lactation were evaluated. Isolates
      were obtained from the Canadian Bovine Mastitis Research Network culture bank and
      were identified to the species level using rpoB gene sequencing. Cow and quarter
      level data were obtained from the Canadian Bovine Mastitis Research Network
      database and used for statistical analyses. In addition, for mammary quarters
      that had more than one isolation of the same CNS species at different time
      points, the isolates were evaluated using pulsed-field gel electrophoresis to
      identify persistent IMI. Milk SCC was compared between mammary quarters infected
      with different CNS species and to a cohort of uninfected mammary quarters. A
      total of 877 isolates from 643 mammary quarters of 555 cows on 89 Canadian dairy
      farms were identified to the species level. Twenty different species were
      identified, with Staphylococcus chromogenes being the most common species
      identified (48% of isolates), followed by Staphylococcus simulans (19%) and
      Staphylococcus xylosus (10%). Of the 20 species identified, only 9 species were
      found in persistently infected quarters. Milk SCC was significantly higher in the
      CNS-infected mammary quarters than in the uninfected control quarters for 8 of
      the 20 species studied. Also, mean SCC differed significantly between mammary
      quarters infected with different CNS species. Within a given species, a high
      degree of variability was noted in milk SCC. These data corroborate recent data
      from Europe with regard to the predominance of certain species of CNS (e.g.,
      Staph. chromogenes). In addition, some species of CNS appear to have a greater
      effect on milk SCC. Finally, some CNS species are associated with persistent IMI
      suggesting that some species (e.g., Staph. chromogenes and Staph. simulans) are
      better host-adapted, whereas others may have an environmental reservoir. 

PMID- 24931525
TI  - Short communication: effect of trans-10,cis-12 conjugated linoleic acid on
      activation of lipogenic transcription factors in bovine mammary epithelial cells.
AB  - The objective of this study was to examine the effect of trans-10,cis-12
      conjugated linoleic acid (t10c12CLA) on the activation of transcription factors
      that potentially regulate lipid synthesis in a bovine mammary epithelial cell
      line (MAC-T). Cells were transfected with luciferase reporter constructs
      containing sterol response element (SRE and SRE complex) for sterol regulatory
      element binding protein-1, peroxisome proliferator response element for
      peroxisome proliferator-activated receptor gamma, or liver X receptor response
      element for liver X receptor. Different concentrations of t10c12CLA (0, 25, 50,
      75, or 100MUM) were applied to cells to determine the activation of transcription
      factors. The influence of t10c12CLA bond structure on transcription factor
      activation was also investigated by treating cells with different 18:1 fatty acid
      isomers (trans-10 18:1 or cis-12 18:1) at 100MUM. Cells were harvested for
      luciferase assay after 24h of treatment. Compared with linoleic acid and cis
      9,trans-11 CLA controls, the SRE reporters had significantly lower activity in
      t10c12CLA-treated cells at 50 and 75MUM for SRE complex and SRE, respectively.
      Lower SRE and SRE complex activation was observed in t10c12CLA treatment at 25,
      50, and 75MUM compared with 0MUM. The peroxisome proliferator response element
      and liver X receptor response element reporters did not respond differently
      between the t10c12CLA treatment and controls. Compared with t10c12CLA, both trans
      10 18:1 and cis-12 18:1 increased the activities of SRE and SRE complex reporters
      by 1.3- to 4.2-fold. In conclusion, t10c12CLA has an inhibitory role in lipogenic
      transcription factor activation of SRE, and this negative effect is due to the
      conjugation of trans-10 and cis-12 double bonds in the fatty acid. Furthermore,
      we found no support for a regulatory role of response elements for peroxisome
      proliferator-activated receptor gamma or liver X receptor in the t10c12CLA
      inhibition of mammary lipid synthesis. 

PMID- 24931526
TI  - Lactose electroisomerization into lactulose: effect of the electrode material,
      active membrane surface area-to-electrode surface area ratio, and interelectrode
      membrane distance.
AB  - The aim of the present work was to study and develop an innovative, clean, and
      environmentally friendly process for lactulose synthesis by electroactivation of
      lactose. In this work, the electrode material (type 304 stainless steel,
      titanium, and copper), dimensionless interelectrode-membrane distance at the
      cathodic compartment (0.36, 0.68, and 1), and the membrane:electrode surface area
      ratio (0.23, 0.06, and 0.015) were considered to be the factors that could affect
      the kinetic conversion of lactose into lactulose. The reactions were conducted
      under an initial lactose concentration of 0.15mol/L at 10 degrees C, Froude
      number (mixing speed) of 2.05*10(-2), and electric current intensity of 300mA for
      30min. The highest lactulose formation yield of 32.50% (0.05mol/L) was obtained
      by using a copper electrode, interelectrode-membrane distance of 0.36, and
      membrane:electrode surface area ratio of 0.23. The 2-parameter Langmuir,
      Freundlich, and Temkin isotherm models were used for the prediction of the
      lactose isomerization kinetics as well as the 3-parameter Langmuir-Freundlich
      isotherm model. It was shown that the lactose isomerization kinetics into
      lactulose followed the Temkin and Langmuir-Freundlich models with coefficients of
      determination of 0.99 and 0.90 and a relative error of 1.42 to 1.56% and 4.27 to
      4.37%, respectively. 

PMID- 24931527
TI  - Comparison of analytical and predictive methods for water, protein, fat, sugar,
      and gross energy in marine mammal milk.
AB  - Mammalian milks may differ greatly in composition from cow milk, and these
      differences may affect the performance of analytical methods. High-fat, high
      protein milks with a preponderance of oligosaccharides, such as those produced by
      many marine mammals, present a particular challenge. We compared the performance
      of several methods against reference procedures using Weddell seal (Leptonychotes
      weddellii) milk of highly varied composition (by reference methods: 27-63% water,
      24-62% fat, 8-12% crude protein, 0.5-1.8% sugar). A microdrying step preparatory
      to carbon-hydrogen-nitrogen (CHN) gas analysis slightly underestimated water
      content and had a higher repeatability relative standard deviation (RSDr) than
      did reference oven drying at 100 degrees C. Compared with a reference macro
      Kjeldahl protein procedure, the CHN (or Dumas) combustion method had a somewhat
      higher RSDr (1.56 vs. 0.60%) but correlation between methods was high (0.992),
      means were not different (CHN: 17.2+/-0.46% dry matter basis; Kjeldahl 17.3+/
      0.49% dry matter basis), there were no significant proportional or constant
      errors, and predictive performance was high. A carbon stoichiometric procedure
      based on CHN analysis failed to adequately predict fat (reference: Rose-Gottlieb
      method) or total sugar (reference: phenol-sulfuric acid method). Gross energy
      content, calculated from energetic factors and results from reference methods for
      fat, protein, and total sugar, accurately predicted gross energy as measured by
      bomb calorimetry. We conclude that the CHN (Dumas) combustion method and
      calculation of gross energy are acceptable analytical approaches for marine
      mammal milk, but fat and sugar require separate analysis by appropriate analytic
      methods and cannot be adequately estimated by carbon stoichiometry. Some other
      alternative methods-low-temperature drying for water determination; Bradford,
      Lowry, and biuret methods for protein; the Folch and the Bligh and Dyer methods
      for fat; and enzymatic and reducing sugar methods for total sugar-appear likely
      to produce substantial error in marine mammal milks. It is important that
      alternative analytical methods be properly validated against a reference method
      before being used, especially for mammalian milks that differ greatly from cow
      milk in analyte characteristics and concentrations. 

PMID- 24931528
TI  - Bovine colostrum: changes in lipid constituents in the first 5 days after
      parturition.
AB  - Despite the great interest paid to protein components in colostrum, fat also
      plays an important role in the supply of essential nutrients to provide energy,
      increase metabolism, and protect the newborn calf against microbial infections.
      This work aimed to elucidate levels of different fat components in colostrum, in
      particular fatty acid (FA), triglyceride (TG), cholesterol, and phospholipid
      contents. Colostrum samples from primiparous and multiparous (3-5 lactations)
      Holstein dams, fed the same ration indoors, were collected on the first 5d after
      parturition, analyzed, and compared with milk samples from the same cows
      collected at 5mo of lactation. Fat content during the first 5d of milking did not
      vary. However, the proportion of short-chain saturated FA increased and that of
      long-chain FA decreased. The concentration of n-3 FA was higher on the first day
      of calving than on the other days, with clear differences in the number and type
      of n-3 FA. Conjugated linoleic isomers and trans FA slowly increased from d 1 to
      5, reaching a maximum at 5mo of lactation. Changes in the distribution profile of
      TG were observed as lactation progressed, with a shift from a prevalence of high
      carbon-number TG (C48-50) on d 1 to a bimodal distribution (maxima at C38 and
      C50) on d 5, characteristic of mid-lactation milk. Cholesterol content was high
      in the first hours after calving and rapidly decreased within 48h. Colostrum
      sampled on d 1 also had a high content of phospholipids. Phosphatidylethanolamine
      and sphingomyelin were, respectively, lower and higher in the first 5d than in
      mid-lactation milk. The influence of lactation number on colostrum fat
      composition was also considered and significant results were obtained for all FA
      groups (except for polyunsaturated and n-6 FA) and TG content. 

PMID- 24931529
TI  - Short communication: effects of milk removal on teat tissue and recovery in
      Murciano-Granadina goats.
AB  - The aim of this work was to study how machine milking (MM) carried out in
      appropriate conditions affects teat wall thickness and canal length and their
      return after milking to premilking conditions compared with other milk removal
      methods considered biological referents: kid suckling (KS), catheter removal
      (CATH), and hand milking (HM). Three Latin square experiments were designed, each
      divided into 2 periods. In the first period, the left glands of each animal were
      machine milked and the KS, CATH, and HM treatments were applied to the right
      glands in experiments 1, 2, and 3, respectively. Subsequently, in the second
      period, the removal methods were interchanged. Teat wall thickness, teat wall
      area, teat end wall area, and teat canal length were measured from the ultrasound
      images. Milk removal using the reference methods (KS, CATH, and HM) and by MM
      caused increases in teat wall thickness and teat canal length, which were greater
      with MM. The time needed for the teat walls and canal to return to their
      physiological conditions before milk removal was greater than 10h in the
      reference methods and following machine milking. 

PMID- 24931530
TI  - The effect of routine hoof trimming on locomotion score, ruminating time,
      activity, and milk yield of dairy cows.
AB  - The objective of this study was to quantify the effect of hoof trimming on cow
      behavior (ruminating time, activity, and locomotion score) and performance (milk
      yield) over time. Data were gathered from a commercial dairy farm in Israel where
      routine hoof trimming is done by a trained hoof trimmer twice per year on the
      entire herd. In total, 288 cows spread over 6 groups with varying production
      levels were used for the analysis. Cow behavior was measured continuously with a
      commercial neck activity logger and a ruminating time logger (HR-Tag, SCR
      Engineers Ltd., Netanya, Israel). Milk yield was recorded during each milking
      session with a commercial milk flow sensor (Free Flow, SCR Engineers Ltd.). A
      trained observer assigned on the spot 5-point locomotion scores during 19
      nighttime milking occasions between 22 October 2012 and 4 February 2013.
      Behavioral and performance data were gathered from 1wk before hoof trimming until
      1wk after hoof trimming. A generalized linear mixed model was used to
      statistically test all main and interactive effects of hoof trimming, parity,
      lactation stage, and hoof lesion presence on ruminating time, neck activity, milk
      yield, and locomotion score. The results on locomotion scores show that the
      proportional distribution of cows in the different locomotion score classes
      changes significantly after trimming. The proportion of cows with a locomotion
      score >=3 increases from 14% before to 34% directly after the hoof trimming. Two
      months after the trimming, the number of cows with a locomotion score >=3 reduced
      to 20%, which was still higher than the baseline values 2wk before the trimming.
      The neck activity level was significantly reduced 1d after trimming (380+/-6
      bits/d) compared with before trimming (389+/-6 bits/d). Each one-unit increase in
      locomotion score reduced cow activity level by 4.488 bits/d. The effect of hoof
      trimming on ruminating time was affected by an interaction effect with parity.
      The effect of hoof trimming on locomotion scores was affected by an interaction
      effect with lactation stage and tended to be affected by interaction effects with
      hoof lesion presence, indicating that cows with a lesion reacted different to the
      trimming than cows without a lesion did. The results show that the routine hoof
      trimming affected dairy cow behavior and performance in this farm. 

PMID- 24931531
TI  - Effect of supplementing essential fatty acids to pregnant nonlactating Holstein
      cows and their preweaned calves on calf performance, immune response, and health.
AB  - The objective was to evaluate the effect of supplementing saturated or
      unsaturated fatty acids (FA) during late gestation of cows and during the
      preweaning period of calves on growth, health, and immune responses of calves.
      During the last 8wk of pregnancy, Holstein cattle (n=96) were fed no fat
      supplement (control), a saturated FA (SFA) supplement enriched in C18:0, or an
      unsaturated FA supplement enriched in the essential FA linoleic acid. Newborn
      calves were fed a milk replacer (MR) with either low linoleic acid (LLA; coconut
      oil) or high linoleic acid (HLA; coconut oil and porcine lard) concentration as
      the sole feedstuff during the first 30d. A grain mix with minimal linoleic acid
      was offered between 31 and 60d of life. At 30 and 60d of life, concentrations of
      linoleic acid in plasma were increased in calves born from dams supplemented with
      essential FA compared with SFA (44.0 vs. 42.5% of total FA) and in calves
      consuming HLA compared with LLA MR (46.3 vs. 40.8% of total FA). Total n-3 FA
      concentration was increased in plasma of calves fed HLA compared with LLA MR
      (1.44 vs. 1.32%) primarily due to increased alpha-linolenic acid. Prepartum
      supplementation with SFA tended to improve dry matter intake (48.8 vs. 46.7kg)
      and improved average daily gain (0.50 vs. 0.46kg/d) by calves without affecting
      efficiency of gain or circulating concentrations of anabolic metabolites or
      hormones. Increasing mean intake of linoleic acid from approximately 4.6 to
      11.0g/d during the first 60d of life increased average daily gain (0.50 vs.
      0.45kg/d) without a change in dry matter intake, thus improving feed efficiency
      (0.63 vs. 0.59kg of gain/kg of dry matter intake). Improved weight gain in calves
      fed HLA MR was accompanied by increased or tendency to increase plasma
      concentrations of glucose (92.7 vs. 89.9g/dL) and insulin-like growth factor I
      (59.5 vs. 53.2g/dL), increased hematocrit (36.0 vs. 34.4%) and concentration of
      blood lymphocytes (4.61 vs. 4.21*10(3)/MUL), lowered plasma concentrations of
      acid-soluble protein (78.8 vs. 91.3mg/L) and blood platelets (736 vs.
      822*10(3)/MUL), and increased production of IFN-gamma by peripheral blood
      mononuclear cells at 30d of age (48.1 vs. 25.6pg/mL), possibly indicating an
      earlier development of the immune system. Partial replacement of coconut oil with
      porcine lard in MR improved calf performance and some aspects of immunity. 

PMID- 24931532
TI  - Effect of early or late resynchronization based on different methods of pregnancy
      diagnosis on reproductive performance of dairy cows.
AB  - The aim of this study was to compare the reproductive performance of dairy cows
      subjected to early (ER) or late (LR) resynchronization programs after
      nonpregnancy diagnoses based on either pregnancy-associated glycoproteins (PAG)
      ELISA or transrectal palpation, respectively. In addition, the accuracy of the
      PAG ELISA for early pregnancy diagnosis was assessed. Lactating Holstein cows
      were subjected to a Presynch-Ovsynch protocol with timed artificial insemination
      (AI) performed between 61 and 74 DIM. On the day of the first postpartum AI,
      1,093 cows were blocked by parity and assigned randomly to treatments; however,
      because of attrition, 452 ER and 520 LR cows were considered for the statistical
      analyses. After the first postpartum AI, cows were observed daily for signs of
      estrus and inseminated on the same day of detected estrus. Cows from ER that were
      not reinseminated in estrus received the first GnRH injection of the Ovsynch
      protocol for resynchronization 2d before pregnancy diagnosis. On d 28 after the
      previous AI (d 27 to 34), pregnancy status was determined by PAG ELISA, and
      nonpregnant cows continued on the Ovsynch protocol for reinsemination. Pregnant
      cows had pregnancy status reconfirmed on d 46 after AI (d 35 to 52) by
      transrectal palpation, and those that lost the pregnancies were resynchronized.
      Cows assigned to LR had pregnancy diagnosed by transrectal palpation on d 46
      after AI (d 35 to 52) and nonpregnant cows were resynchronized with the Ovsynch
      protocol. Blood was sampled on d 28 after AI (d 27 to 34) from cows in both
      treatments that had not been reinseminated on estrus and again on d 46 after AI
      (d 35 to 52) for assessment of PAG ELISA to determine the accuracy of the test.
      Cows were subjected to treatments for 72d after the first insemination. Pregnancy
      per AI (P/AI) at first postpartum timed AI did not differ between treatments and
      averaged 28.9%. The proportion of nonpregnant cows that were resynchronized and
      received timed AI was greater for ER than for LR (30.0 vs. 7.6%). Cows in ER had
      a shorter interval between inseminations when inseminated following spontaneous
      estrus (21.7+/-1.1 vs. 27.8+/-0.8d) or after timed AI (35.3+/-1.2 vs. 55.2+/
      1.4d). Nevertheless, the ER did not affect the rate of pregnancy (adjusted hazard
      ratio=1.23; 95% confidence interval=0.94 to 1.61) or the median days postpartum
      to pregnancy (ER=132 vs. LR=140). A total of 2,129 PAG ELISA were evaluated.
      Overall, sensitivity, specificity, and positive and negative predictive values
      averaged 95.1, 89.0, 90.1, and 94.5%, respectively, and the accuracy was 92.1%.
      In conclusion, PAG ELISA for early diagnosis of pregnancy had acceptable
      accuracy, but early resynchronization after nonpregnancy diagnosis with PAG ELISA
      did not improve the rate of pregnancy or reduce days open in dairy cows
      continuously observed for estrus. 

PMID- 24931533
TI  - Cellular proliferation rate and insulin-like growth factor binding protein
      (IGFBP)-2 and IGFBP-3 and estradiol receptor alpha expression in the mammary
      gland of dairy heifers naturally infected with gastrointestinal nematodes during
      development.
AB  - Mammary ductal morphogenesis during prepuberty occurs mainly in response to
      insulin-like growth factor-1 (IGF-1) and estradiol stimulation. Dairy heifers
      infected with gastrointestinal nematodes have reduced IGF-1 levels, accompanied
      by reduced growth rate, delayed puberty onset, and lower parenchyma-stroma
      relationship in their mammary glands. Immunohistochemical studies were undertaken
      to determine variations in cell division rate, IGF-1 system components, and
      estradiol receptors (ESR) during peripubertal development in the mammary glands
      of antiparasitic-treated and untreated Holstein heifers naturally infected with
      gastrointestinal nematodes. Mammary biopsies were taken at 20, 30, 40, and 70 wk
      of age. Proliferating cell nuclear antigen immunolabeling, evident in nuclei,
      tended to be higher in the parenchyma of the glands from treated heifers than in
      those from untreated. Insulin-like growth factor binding proteins (IGFBP) type 2
      and type 3 immunolabeling was cytoplasmic and was evident in stroma and
      parenchyma. The IGFBP2-labeled area was lower in treated than in untreated
      heifers. In the treated group, a maximal expression of this protein was seen at
      40 wk of age, whereas in the untreated group the labeling remained constant. No
      differences were observed for IGFBP3 between treatment groups or during
      development. Immunolabeling for alpha ESR (ESR1) was evident in parenchymal
      nuclei and was higher in treated than in untreated heifers. In the treated group,
      ESR1 peaked at 30 wk of age and then decreased. These results demonstrate that
      the parasite burden in young heifers negatively influence mammary gland
      development, affecting cell division rate and parameters related to estradiol and
      IGF-1 signaling in the gland. 

PMID- 24931534
TI  - Diets rich in starch increase the posthepatic availability of amino acids in
      dairy cows fed diets at low and normal protein levels.
AB  - Five mid-lactation multicatheterized Jersey cows were used in a 4*4 Latin square
      design to investigate whether the increase in milk N yield associated with diets
      rich in starch versus fiber could originate from changes in the splanchnic AA
      metabolism and if these changes depended upon the dietary crude protein (CP)
      content. Four isoenergetic diets were formulated to provide 2 different
      carbohydrate compositions [diets rich in starch (350g of starch and 310g of
      neutral detergent fiber/kg of dry matter) versus rich in fiber (45g of starch and
      460g of neutral detergent fiber/kg of dry matter)] crossed by 2 different CP
      contents (12.0 vs. 16.5% CP). At the end of each treatment period, 6 hourly blood
      samples were collected from the portal and hepatic veins as well as the
      mesenteric artery to determine net nutrient fluxes across the portal-drained
      viscera (PDV), liver, and total splanchnic tissues. Dry matter and calculated
      energy intake as well as total absorbed energy were similar across treatments.
      However, the net portal appearance (NPA) of acetate, total volatile fatty acids,
      and beta-hydroxybutyrate were higher with diets rich in fiber versus starch,
      whereas that of oxygen, glucose, butyrate, and insulin were lower. Concomitant to
      these changes, the percentage of N intake recovered as total AA (TAA) in the
      portal vein was lower for diets rich in fiber versus starch (42.3 vs. 51.4%,
      respectively), without, however, any difference observed in the NPA of the main
      AA used as energy fuels by the PDV (Glu, Gln, and Asp). Despite a higher NPA of
      TAA with starch versus fiber diets, no differences in the net hepatic flux of
      TAA, essential and nonessential AA were observed, resulting in a higher (+22%)
      net splanchnic release of AA and, hence, a greater (+7%) milk N yield. The net
      hepatic flux and hepatic fractional removal of none of the individual AA was
      affected as the main carbohydrate changed from fiber to starch, except for Gly
      and Lys, which were higher for the latter. After correcting for differences in
      NPA of TAA, the net hepatic uptake of TAA tended to be lower with starch versus
      fiber diets. The higher transfer of N from feed to milk with diets rich in starch
      is not the consequence of a direct sparing AA effect of glucogenic diets but
      rather the result of lower energy requirements by the PDV along with a higher
      microbial N flow to the duodenum. A better AA use by peripheral tissues with
      starch versus fiber diets was also hypothesized but more studies are warranted to
      clarify this issue. 

PMID- 24931535
TI  - Influence of geochemical properties and land-use types on the microbial reduction
      of Fe(III) in subtropical soils.
AB  - Microbial Fe(III) reduction significantly impacts the geochemical processes and
      the composition of most subsurface soils. However, up to now, the factors
      influencing the efficiency of Fe(III) reduction in soils have not been fully
      described. In this study, soil Fe(III) reduction processes related to geochemical
      properties and land-use types were systematically investigated using iron-rich
      soils. The results showed that microbial Fe(III) reduction processes were
      efficient and their rates varied significantly in different types of soils.
      Fe(III) reduction rates were 1.1-5.6 times as much in soils with glucose added as
      in those without glucose. Furthermore, Fe(III) reduction rates were similar in
      soils from the same parent materials, while they were highest in soils developed
      from sediments, with a mean rate of 1.87 mM per day when supplemented with
      glucose. In addition, the Fe(III) reduction rates, reaching 0.99 and 0.59 mM per
      day on average with and without glucose added, respectively, were higher in the
      paddy soils affected heavily by human activities than those in the forest soils
      (average rates of 0.38 and 0.15 mM per day when with and without glucose,
      respectively). All the soil weathering indices correlated linearly with Fe(III)
      reduction rates, even though the reduction of iron in soils with higher
      weathering degrees was partly inhibited by a higher soil protonation trend and
      fewer available iron reduction sites in the soils, which gives lower reduction
      rates. These results clearly illustrate that soil Fe(III) reduction rates are
      greatly dependent on soil geochemical properties and land-use types and help
      define which soil types exhibit similar degrees of Fe(III) reduction under field
      conditions.

PMID- 24931536
TI  - Editorial.

PMID- 24931537
TI  - Anxiety disorders: under-diagnosed and insufficiently treated.
AB  - Anxiety disorders have a high prevalence, particularly specific phobia, social
      anxiety disorder (SAD), post-traumatic stress disorder (PTSD) and generalized
      anxiety disorder (GAD). The lifetime prevalence for any anxiety disorder is
      almost 30%. Also, many anxiety disorders have a high rate of comorbid depression,
      which is generally secondary to the anxiety. Despite high prevalence, anxiety
      disorders are under-diagnosed, misdiagnosed and inappropriately treated. There is
      a hierarchy in the lifetime probability of treatment contact, with panic and GAD
      being diagnosed and treated earlier - possibly as a result of these disorders
      being the most "visible", unlike SAD, which is characteristically discreet. Under
      diagnosis is linked with under-treatment: less than one in five patients with an
      anxiety disorder receive appropriate medication, which improves to almost one in
      three for subjects with comorbid depression. For the majority of people with
      undiagnosed or untreated anxiety disorder, there are many negative consequences,
      for both the individual and society. These include disability, reduced ability to
      work leading to loss of productivity, and a high risk of suicide. All of these
      factors contribute to a reduced quality of life. The economic costs associated
      with anxiety disorders are large - ?48 billion over 28 European countries - and
      similar to those for dementia. Almost half of the costs are indirect, due to loss
      of productivity and earnings; the remainder being direct medical and non-medical
      costs. Current first-line therapies are the antidepressive selective serotonin
      reuptake inhibitors (SSRIs), with cognitive behavioural therapy a first- or
      second-line treatment. However, benzodiazepines continue to be prescribed more
      often than antidepressants. Recent studies have shown that a new type of SSRI,
      escitalopram (the S-enantiomer of the racemic citalopram), with a unique mode of
      action, is effective and offers potential as a new treatment for anxiety
      disorders. 

PMID- 24931538
TI  - Generalized anxiety disorder: how to treat, and for how long?
AB  - Generalized anxiety disorder (GAD) is a common, chronic and disabling anxiety
      disorder with considerable comorbidity with depression as well as with other
      anxiety disorders. Although tricyclic antidepressants and benzodiazepines have
      been found to be efficacious in patients with GAD, tolerability problems and
      other risks limit their use in clinical practice. In placebo-controlled, acute
      (<8 weeks) trials, several medications, including the selective serotonin
      reuptake inhibitors ([SSRIs] escitalopram, paroxetine, and sertraline) and others
      (venlafaxine, buspirone, pregabalin), have demonstrated efficacy in patients with
      GAD. Indeed, current guidelines for the treatment of GAD recommend SSRIs as first
      line pharmacological therapy because of their efficacy and tolerability profiles.
      Although GAD is a chronic condition that is usually present for years, with
      symptoms typically fluctuating in intensity over time, there have been few
      randomized, controlled trials of pharmacotherapy beyond the acute phase of
      treatment. However, data from recent relapse-prevention studies and longer-term
      maintenance studies with paroxetine, venlafaxine and escitalopram strongly
      support the value of continued treatment for at least a further 6 months. This
      article focuses on pharmacological treatment, and reviews recently available data
      from acute, long-term and relapse-prevention trials in patients with GAD. In
      addition, issues relating to the natural course of GAD are highlighted as
      important considerations to guide selection of pharmacotherapy. 

PMID- 24931539
TI  - Evidence-based treatment of anxiety disorders.
AB  - Evidence-based medicine combines the best currently available evidence from
      systematic medical research, together with clinical expertise, in order to
      provide the best available care for patients. In conjunction with systematic
      reviews (meta-analyses), a critical review of evidence-based literature forms the
      basis for the development of clinical treatment guidelines. Current treatment
      guidelines for generalized anxiety disorder (GAD) advocate the use of selective
      serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake
      inhibitors (SNRIs) as the first line of pharmacotherapy. The safety and
      tolerability profiles of other medications, such as the benzodiazepines, limit
      their use, especially for long-term treatment. Since data comparing the efficacy
      in GAD of different SSRIs are limited, selection of one SSRI over another is
      generally based on consideration of tolerability profiles. Treatment guidelines
      for patients with social anxiety disorder (SAD) often recommend SSRIs as the
      first line of medication treatment, as this class has the largest evidence-base
      in support of efficacy. Less consistent evidence of efficacy exists for other
      agents, such as reversible inhibitors of monoamine oxidase inhibitor A (RIMAs),
      and issues of safety are a concern when considering the use of benzodiazepines.
      Again, there are few head-to-head studies of the SSRIs, and treatment selection
      is usually made on the basis of tolerability issues. The efficacy and
      tolerability of the SSRI, escitalopram, has been evaluated in patients with GAD
      and with SAD. In long-term studies of SAD, escitalopram demonstrated superior
      efficacy to placebo and paroxetine. It also exhibited a better tolerability
      profile, as assessed by discontinuation emergent signs and symptoms (DESS), in
      both patient groups. Furthermore, in relapse prevention trials of SAD,
      escitalopram conferred a significant benefit relative to placebo. 

PMID- 24931540
TI  - Current treatment options: relief of symptoms and ultimate recovery.
AB  - The inadequate outcome of existing antidepressant therapies has led to a shift in
      the expectations of optimal treatment toward remission rather than response.
      Important benchmarks for newer antidepressant treatments in the management of
      major depressive disorder (MDD) include early response and remission leading to
      recovery, regardless of severity. Preliminary data from a pooled analysis of
      trials, in which escitalopram was compared with selective serotonin reuptake
      inhibitors (SSRIs) and the selective serotonin noradrenaline reuptake inhibitor
      (SNRI) venlafaxine, suggest a faster onset of action compared with other SSRIs.
      In a further pooled analysis, a significant advantage in response and remission
      in favor of escitalopram against comparator SSRIs and venlafaxine was
      demonstrated. Studies appear to suggest that not only is escitalopram effective
      in depression, its superiority over comparators increases with baseline severity.
      Thus, escitalopram may satisfy many of the goals for the new generation of
      antidepressants in the management of MDD. 

PMID- 24931541
TI  - Quality of life in depression and anxiety: does it matter?
AB  - Quality of life (QoL) is an assessment going beyond symptom control that
      investigates positive effects, life satisfaction, well-being, impairment and
      functioning of a patient. Compared with patients with other common medical
      disorders, patients with mood (and to a lesser extent) anxiety disorders exhibit
      an impairment that pervades all dimensions of the QoL scale. There are function-
      and needs-based approaches to QoL measurement. The availability of numerous QoL
      scales also prompt careful selection, as different scales stem from varying
      notions of QoL. Although the effect size of pharmacological treatment on QoL
      scales is usually smaller than on symptom scales, it is nevertheless clinically
      significant. Newer antidepressants, such as escitalopram, have been shown to
      improve QoL in patients with depression and anxiety disorders. Increased
      assessment of QoL should be encouraged in future trials, to improve the
      understanding of treatment impact on overall well-being, in patients with
      depression and anxiety disorders. 

PMID- 24931542
TI  - The importance of long-term tolerability in achieving recovery.
AB  - Many patients with depression require long-term treatment to provide optimal
      clinical outcomes. Long-term tolerability is therefore important in facilitating
      adherence to treatment and thereby maintaining control over depressive symptoms.
      While the newer selective serotonin reuptake inhibitors (SSRIs) and serotonin
      noradrenaline reuptake inhibitors (SNRIs) are generally better tolerated than
      older treatments, such as tricyclic antidepressants and monoamine oxidase
      inhibitors, they can still cause nausea, headache, sleep disturbances, dry mouth,
      weight gain and sexual dysfunction. However, SSRIs and SNRIs differ in the extent
      to which they are associated with adverse events. Available data suggest that
      treatment of depression with escitalopram (an SSRI) may result in fewer side
      effects than citalopram or paroxetine (other SSRIs), or venlafaxine (an SNRI).
      Adverse events decrease with time during long-term escitalopram treatment, and in
      one study, after a 52-week escitalopram treatment, fewer than 10% of patients had
      withdrawn due to adverse events. Escitalopram is well tolerated during long-term
      treatment and appears better tolerated than some other SSRIs and venlafaxine.
      This improved tolerability is particularly important when selecting an
      antidepressant for long-term use. 

PMID- 24931543
TI  - Sleep problems in depression: how do they impact treatment and recovery?
AB  - Chronic insomnia is common, although its prevalence in the general population is
      quite variable, depending on definitions used and the populations surveyed.
      Studies indicate that as many as 85% of people with serious insomnia remain
      untreated. Insomnia is frequently comorbid with depression, and observational
      studies suggest that insomnia is a high risk factor for depression. Disturbed
      sleep is of particular concern in patients with depression, as it can aggravate
      the symptoms of depression and influence the treatment response to
      antidepressants. Many antidepressants, including some selective serotonin
      reuptake inhibitors (SSRIs), can disrupt sleep architecture, particularly in the
      acute phase of treatment. Although this undesirable effect may not be immediately
      apparent in patients with depression, because of their high level of sleep
      disruption at baseline, it may nevertheless contribute to reduced compliance with
      therapy. In some patients, persistent insomnia may be a valuable clue to
      treatment resistance. Thus, it is essential to monitor sleep patterns in patients
      being treated for depression and to adequately address any sleep problems as they
      arise during the whole depressive episode. Optimal therapy for depression-related
      insomnia has not yet been established. Co-administration of a hypnotic drug such
      as zolpidem may help some patients avoid the sleep-disrupting adverse effect of
      some antidepressants. Selection of an antidepressant with sedating effects is
      another alternative that may be beneficial for some patients, although daytime
      somnolence may limit use in some cases. New SSRIs, such as escitalopram, which
      may be less disruptive to sleep and possibly preserve sleep continuity without
      sedation, may be the preferred option for some patients. 

PMID- 24931544
TI  - Chondroma of the diaphragm mimicking a giant liver tumor with calcification:
      report of a case.
AB  - Extraskeletal chondroma is an unusual benign tumor, which rarely arises in the
      diaphragm. We report a case of chondroma of the diaphragm in a 31-year-old woman.
      Initially, a benign liver tumor with calcification was suspected, based on pre
      and intraoperative examination findings. Although parts of the tumor were
      contiguous with the diaphragm, its connections with the diaphragm were much
      narrower than its connection with the liver, which suggested a liver tumor.
      Pathological examination subsequently revealed that the chondroma was contiguous
      with the diaphragm and that there was a distinct border between the tumor and the
      liver; thus, the tumor was diagnosed as a chondroma of the diaphragm. 

PMID- 24931545
TI  - Histological analysis of appendices removed during interval appendectomy after
      conservative management of pediatric patients with acute appendicitis with an
      inflammatory mass or abscess.
AB  - BACKGROUND/PURPOSE: To clarify the role of interval appendectomy (IA) in
      pediatric patients with acute appendicitis with an appendiceal inflammatory mass
      or abscess, we histologically analyzed the appendices removed during IA. PATIENTS
      AND METHODS: We treated 355 consecutive pediatric patients with acute
      appendicitis and reviewed the admission charts of patients who started
      conservative management (CM). The histology of the appendix removed during IA was
      also examined. The relationships among the clinical features, appendicolith
      formation at the time of IA and histological findings were analyzed by stepwise
      regression analyses. RESULTS: (1) CM was started in 48 patients (13.5 %).
      Recurrence or a remaining abscess was observed in nine patients (18.8 %). (2)
      Histopathological changes, particularly foreign body reaction with fibrosis and
      infiltration of inflammatory cells, were observed in about half of the specimens.
      (3) In a stepwise regression analysis, the presence of an appendicolith at IA was
      correlated with an appendicolith at diagnosis, foreign body reaction in the
      appendix and a decrease in the inflammatory reaction at diagnosis. CONCLUSION:
      More than half the patients had strong histopathological changes in the appendix,
      suggesting a high possibility of recurrence. The presence of appendicolith
      formation at IA, which is a risk factor for recurrence, was influenced by the
      presence of an appendicolith at diagnosis, foreign body reaction in the appendix
      and the inflammatory status of patients at diagnosis. These clinical findings are
      indications for IA.

PMID- 24931546
TI  - Differentiating nocturnal leg cramps and restless legs syndrome.
AB  - Leg pain and discomfort are common complaints in any primary physician's clinic.
      Two common causes of pain or discomfort in legs are nocturnal leg cramps (NLC)
      and restless leg syndrome (RLS). NLC present as painful and sudden contractions
      mostly in part of the calf. Diagnosis of NLC is mainly clinical and sometimes
      involves investigations to rule out other mimics. RLS is a condition
      characterized by the discomfort or urge to move the lower limbs, which occurs at
      rest or in the evening/night. The similarity of RLS and leg cramps poses the
      issue of errors in diagnosing and differentiating the two. In this paper we
      review the pathopysiology of each entity and their diagnosis as well as
      treatment. The two conditions are then compared to appreciate the differences and
      similarities. Finally, suggestions are recommended for complete assessment. 

PMID- 24931547
TI  - Nanomechanical sensors for single microbial cell growth monitoring.
AB  - A nanomechanical technique for rapid real time detection and monitoring of
      microorganism growth will significantly reduce costs and diagnosis times in
      industrial and clinical settings. Owing to their label free detection mechanism
      and unprecedented sensitivity to the mass and elastic modulus of biological
      structures, dynamically operated cantilever arrays provide an opportunity to
      rapidly detect and track the evolution of microbial growth. Here we report the
      monitoring of the growth of single Aspergillus niger spores via the multimode
      response of microcantilevers. The fungal hyphal structure affects the
      cantilevers' nanomechanical properties as it propagates along the sensor. We
      demonstrate, for the first time, the mapping of cellular events with great
      accuracy using a cantilever frequency response. Imaging of growth conditions on
      the cantilever, which is performed in parallel, allows for verification of these
      results. Theoretical comparison and finite element modelling confirm experimental
      findings and allow for determination of the hyphal elastic modulus. 

PMID- 24931548
TI  - Preceding human metapneumovirus infection increases adherence of Streptococcus
      pneumoniae and severity of murine pneumococcal pneumonia.
AB  - BACKGROUND: Coinfection with respiratory virus and Streptococcus pneumoniae has
      been frequently reported in several epidemiologic studies. The aim of this study
      was to explore the effect of preceding human metapneumovirus (hMPV) inoculation
      on subsequent pneumococcal infection. METHODS: Hep-2 and A549 cells were infected
      with hMPV then inoculated with S. pneumoniae. Bacterial adhesion was measured
      using colony forming unit and cytometric-fluorescence assays. In vivo bacterial
      adhesion was examined in hMPV-infected mice after inoculation of fluorescence
      conjugated S. pneumoniae. Pulmonary inflammation (bacterial titers, cytokine
      levels, and histopathology) of hMPV-infected mice was investigated after
      inoculation with S. pneumoniae. RESULTS: In vitro results of bacterial infection
      with S. pneumoniae on A549 and Hep-2 monolayer cells showed that even though
      cellular adherence was variable among different serotypes, there was
      significantly enhanced bacterial adherence in A549 cells with preceding hMPV
      infection. In addition, in vivo study of hMPV-infected mice showed increased
      adhesion of S. pneumoniae on the bronchial epithelium with delayed bacterial
      clearance and exacerbated histopathology. Furthermore, mice with preceding hMPV
      infection showed repressed recruitment of airway neutrophils with decreased
      expression of neutrophil chemoattractants during pneumococcal infection.
      CONCLUSION: These results suggest that hMPV-infected airway cells, especially the
      lower airway epithelium, express increased adherence with S. pneumoniae.
      Furthermore, hMPV-infected mice showed impaired recruitment of airway
      neutrophils, possibly leading to delayed bacterial clearance and exacerbated
      pulmonary inflammation, after secondary infection with pneumococcal isolates.

PMID- 24931549
TI  - A heterogeneous biotin-streptavidin-amplified enzyme-linked immunosorbent assay
      for detecting tris(2,3-dibromopropyl) isocyanurate in natural samples.
AB  - Tris(2,3-dibromopropyl) isocyanurate (TBC) is a novel brominated flame retardant
      (BFR) that is widely used to substitute the prohibited BFRs throughout the world.
      With the development of research, the potential environmental and ecological
      harms of TBC have been revealed. For sensitive and selective detecting TBC, an
      indirect competitive biotin-streptavidin-amplified enzyme-linked immunosorbent
      assay (BA-ELISA) has been established in this study. The small molecular TBC
      hapten was synthesized first; it mimicked the chemical structure of TBC and
      possessed a secondary amine group. The as-obtained hapten was then conjugated
      with carrier proteins to prepare artificial antigen. After immunization, the anti
      TBC polyclonal antibody was obtained from separating rabbit serum. The procedures
      of this BA-ELISA were optimized. Under the optimal conditions, the limit of
      detection (IC10) was 0.0067 ng/ml and the median inhibitory concentration (IC50)
      was 0.66 ng/ml. Cross-reactivity values of the BA-ELISA with the tested TBC
      analogues were ?5%. This immunoassay was successfully applied to determine the
      TBC residue in river water samples that were collected near a BFR manufacturing
      plant. Satisfactory recoveries (92.1-109.2%) were obtained. The results indicated
      that this proposed BA-ELISA is suitable for the rapid and sensitive determining
      of TBC in environmental monitoring.

PMID- 24931550
TI  - Conformational dynamics of Thermus aquaticus DNA polymerase I during catalysis.
AB  - Despite the fact that DNA polymerases have been investigated for many years and
      are commonly used as tools in a number of molecular biology assays, many details
      of the kinetic mechanism they use to catalyze DNA synthesis remain unclear.
      Structural and kinetic studies have characterized a rapid, pre-catalytic open-to
      close conformational change of the Finger domain during nucleotide binding for
      many DNA polymerases including Thermus aquaticus DNA polymerase I (Taq Pol), a
      thermostable enzyme commonly used for DNA amplification in PCR. However, little
      has been performed to characterize the motions of other structural domains of Taq
      Pol or any other DNA polymerase during catalysis. Here, we used stopped-flow
      Forster resonance energy transfer to investigate the conformational dynamics of
      all five structural domains of the full-length Taq Pol relative to the DNA
      substrate during nucleotide binding and incorporation. Our study provides
      evidence for a rapid conformational change step induced by dNTP binding and a
      subsequent global conformational transition involving all domains of Taq Pol
      during catalysis. Additionally, our study shows that the rate of the global
      transition was greatly increased with the truncated form of Taq Pol lacking the N
      terminal domain. Finally, we utilized a mutant of Taq Pol containing a de novo
      disulfide bond to demonstrate that limiting protein conformational flexibility
      greatly reduced the polymerization activity of Taq Pol. 

PMID- 24931552
TI  - Agenesis of ductus venosus in sequential first and second trimester screening.
AB  - OBJECTIVE: The goal of this study is to evaluate the potential of first trimester
      (FT) screening in the diagnosis of agenesis of the ductus venosus (ADV) and to
      study its prevalence in a low-risk population, the associated conditions, and
      pregnancy outcome. METHOD: Prospective, sequential screening study at two
      tertiary units with morpho-functional evaluation of the ductus venosus during the
      first and second trimester screening. We quantified the FT detection rate,
      prevalence, and associated conditions: umbilical shunting type, concomitant
      anomalies, and outcome. RESULTS: In 6114 consecutive pregnancies, we identified
      11 cases of ADV. Ten (91%) were identified during the FT examination. The
      prevalence was 1 in 556, similar for both centers (1/478 vs. 1/691). Major
      structural defects and fetal effusions were detected in 8 (73%). twenty two
      percent had a major chromosomal abnormality. In 3 cases, the anomaly was isolated
      and had normal outcome, independent of liver by-pass, caliber of the shunt, and
      NT thickness. CONCLUSIONS: Agenesis of the ductus venosus can be detected during
      FT. The early detection of ADV is important given its high association with major
      abnormalities.

PMID- 24931551
TI  - Imatinib activates pathological hypertrophy by altering myocyte calcium
      regulation.
AB  - BACKGROUND: Imatinib mesylate is a selective tyrosine-kinase inhibitor used in
      the treatment of multiple cancers, most notably chronic myelogenous leukemia.
      There is evidence that imatinib can induce cardiotoxicity in cancer patients. Our
      hypothesis is that imatinib alters calcium regulatory mechanisms and can
      contribute to development of pathological cardiac hypertrophy. METHODS AND
      RESULTS: Neonatal rat ventricular myocytes (NRVMs) were treated with clinical
      doses (low: 2 MUM; high: 5 MUM) of imatinib and assessed for molecular changes.
      Imatinib increased peak systolic Ca(2+) and Ca(2+) transient decay rates and
      Western analysis revealed significant increases in phosphorylation of
      phospholamban (Thr-17) and the ryanodine receptor (Ser-2814), signifying
      activation of calcium/calmodulin-dependent kinase II (CaMKII). Imatinib
      significantly increased NRVM volume as assessed by Coulter counter, myocyte
      surface area, and atrial natriuretic peptide abundance seen by Western. Imatinib
      induced cell death, but did not activate the classical apoptotic program as
      assessed by caspase-3 cleavage, indicating a necrotic mechanism of death in
      myocytes. We expressed AdNFATc3-green fluorescent protein in NRVMs and showed
      imatinib treatment significantly increased nuclear factor of activated T cells
      translocation that was inhibited by the calcineurin inhibitor FK506 or CaMKII
      inhibitors. CONCLUSION: These data show that imatinib can activate pathological
      hypertrophic signaling pathways by altering intracellular Ca(2+) dynamics. This
      is likely a contributing mechanism for the adverse cardiac effects of imatinib.

PMID- 24931554
TI  - Mother-adolescent monitoring dynamics and the legitimacy of parental authority.
AB  - This multi-informant longitudinal study aimed to understand whether the family
      dynamics that underlie adolescent voluntary disclosure regarding their leisure
      time behavior differs when adolescents strongly or weakly endorse the legitimacy
      of parental authority. Longitudinal linkages between parental monitoring
      behaviors and adolescents' secrecy and disclosure were tested among youths with
      strong and weak legitimacy beliefs. The sample included 197 adolescents (51%
      female, M age 12 years) and their mothers. Mothers reported on several of their
      own monitoring efforts (i.e., solicitation, active involvement, observing and
      listening, and obtaining information from spouses, siblings, and others).
      Adolescents reported their disclosure, secrecy, and legitimacy beliefs. Only
      among youths reporting strong legitimacy beliefs, more mother engagement and
      supervision (indexed by mother-reported active involvement and observing and
      listening) predicted more adolescent disclosure and less secrecy over time, and
      more mother solicitation predicted less secrecy. 

PMID- 24931553
TI  - The associations between self-consciousness and internalizing/externalizing
      problems among Chinese adolescents.
AB  - Self-consciousness is considered as a multifaceted and hierarchical construct
      that includes self-evaluation, self-experience, and self-control. This study
      assumes that self-consciousness is a preventative factor of internalizing and
      externalizing problems among Chinese adolescents. 1202 Chinese adolescents from
      grade 7 to grade 12 participated in this study by completing a battery of
      questionnaires that assessed self-consciousness and internalizing/externalizing
      problems. The results showed that, after controlling demographic variables, some
      lower-order factors (i.e., sense of satisfaction, sense of anxiety, social self,
      self-restraint, self-esteem, and self-monitoring) and higher-order subscales
      (i.e., self-evaluation and self-experience) of self-consciousness significantly
      predicted internalizing problems, while externalizing problems were predicted by
      several lower-order factors (i.e., self-restraint, sense of satisfaction, and
      self-monitoring) and higher-order subscales (i.e., self-control and self
      experience). In conclusion, this study demonstrates that Chinese adolescents'
      internalizing and externalizing problems are related with different aspects of
      self-consciousness, which sheds light on the prevention into adolescents' problem
      behaviors. 

PMID- 24931555
TI  - Brief report: value priorities of early adolescents.
AB  - Although adolescence is considered to be the formative period of values,
      relatively few studies have addressed values held by adolescents. The present
      short-term longitudinal study explores value priorities of early adolescents from
      two social groups (among ethnic Estonians and Russian-speaking minority) in terms
      of the 10 value types defined by Schwartz, and the question whether values change
      during one year. 575 early adolescents filled out a 21-item version of the
      Portrait Values Questionnaire. Adolescents' value priorities differed from the
      pan-cultural value hierarchy of adults (Bardi, Lee, Hoffmann-Towfigh, & Soutar,
      2009) by attributing more importance to hedonism and stimulation, and less
      importance to benevolence and conformity. Although Russian-speaking students
      rated Self-Enhancement and Openness to Change more highly than Estonians, the
      value hierarchy of adolescents from two social groups was rather similar. Boys
      considered Self-Enhancement more important than girls. More value change was
      observable in Russian-speaking students, and boys. 

PMID- 24931556
TI  - The health diagnoses of homeless adolescents: a systematic review of the
      literature.
AB  - BACKGROUND: Homelessness during adolescence impacts negatively upon young
      people's physical and mental wellbeing. To be effective, programs aimed at
      addressing the health needs of this population must include knowledge of both the
      presenting and underlying acute and chronic conditions that characterise this
      high risk group of youth. METHODS: We undertook a systematic review of the
      international literature for studies that used validated instruments and
      techniques to diagnose prevalence rates of physical and mental health disorders
      in homeless adolescents. RESULTS: Twenty-one studies fulfilled the selection
      criteria. Of these, nine studies examined mental health diagnoses including
      depression, post-traumatic stress disorder, anxiety and substance abuse
      disorders. With one exception, the remaining twelve studies all related to
      sexually transmitted infections. CONCLUSION: Homeless adolescents are diagnosed
      with widely varying rates of mental health disorders and high rates of sexually
      transmitted infection. Other likely chronic and acute physical conditions appear
      to be neglected in the published research.

PMID- 24931557
TI  - Social control and strenuous exercise among late adolescent college students:
      parents versus peers as influence agents.
AB  - In the context of a model of health-related social control, we compared the
      associations among social control strategies, affective and behavioral reactions,
      and exercise for parental and peer influence agents. Late adolescent college
      students (n = 227) completed questionnaires that focused on social control from a
      parent or a peer who attempted to increase their exercising. Results from this
      cross-sectional study revealed that most relationships in the model were similar
      for parent and peer influence agents, however, (a) negative social control was a
      stronger predictor of reactance among parents than peers; (b) positive affect was
      a stronger predictor of attempts to change among peers than parents; and (c)
      positive affect predicted frequency of strenuous exercise only among parents.
      Decreasing parents' use of negative social control strategies and increasing
      adolescents' positive affective reactions to parental social control agents may
      be keys to promoting positive lifestyle changes in late adolescence.

PMID- 24931558
TI  - Connection to parents and healthy separation during adolescence: a longitudinal
      perspective.
AB  - The purpose of our study was to investigate how connection between parents and
      children influences the child's healthy separation during adolescence. We
      analyzed 3 waves of panel data from a study (Flourishing Families Project) of 500
      families with children who were 10-13 years old at Time 1. This study includes
      information from the perspective of the child and his/her mother over a 4 year
      period for two-parent families and mother-headed households. Findings supported
      our hypothesis that a mutual sense of connection between mothers and adolescents
      supported the adolescent's healthy separation over time, with differences due to
      sex of the child, ethnicity and income. Pubertal maturation was negatively
      associated with the sense of connection between adolescents and mothers in our
      sample of young adolescents. We discuss these findings in relation to previous
      literature. 

PMID- 24931559
TI  - Early adolescent Body Mass Index and the constructed environment.
AB  - Previous research has shown that macro-level environmental features such as
      access to walking trails and recreational facilities are correlated with
      adolescent weight. Additionally, a handful of studies have documented
      relationships between micro-level environmental features, such as the presence
      (or absence) of a television in the bedroom, and adolescent weight. In this
      exploratory study we focus exclusively on features of the micro-level environment
      by examining objects that are found within adolescent personal bedrooms in
      relation to the adolescent occupant's Body Mass Index score (BMI). Participants
      were 234 early adolescents (eighth graders and ninth graders) who lived with both
      biological parents and who had their own private bedroom. Discriminant analyses
      were used to identify the bedrooms belonging to adolescents with below and above
      average BMI using objects contained within the micro-level environment as
      discriminating variables. Bedrooms belonging to adolescents with above average
      BMI were more likely to contain objects associated with sedentary behavior (e.g.,
      magazines, electronic games, dolls), whereas the bedrooms belonging to the
      average and below average BMI adolescents were more likely to contain objects
      that reflect past physical activity (e.g., trophies, souvenirs, pictures of
      places that they had visited). If causal connections between micro-environmental
      variables and adolescent BMI can be established in future longitudinal research,
      environmental manipulations may affect adolescent BMI. 

PMID- 24931560
TI  - Dominance as part of self-concept mediates the intergenerational transmission of
      social anxiety among adolescents under residential care.
AB  - According to Rapee (1997), maternal social anxiety (SA) is directly associated
      with adolescent SA because maternal SA causes overprotective and controlling
      parental behavior. A total of 127 adolescents who were in the process of
      transitioning to a boarding school for at-risk youth as well as their mothers
      participated in the current study, 30% of the adolescents had experienced at
      least one depressive episode; 17.5% had been diagnosed with SA. We analyzed an
      expanding model of mediation, of maternal SA and depression in which
      specifically, adolescent self-perception was constructed as a latent factor that
      was formed by self-reported dominance and self-criticism. The results supported
      our hypotheses that maternal SA is not directly associated with adolescent SA.
      Rather, these relationships are mediated by adolescents' self-perception (i.e.,
      dominance and self-criticism). The results call into question Rapee's theoretical
      arguments and support Gilbert's evolutionary theory. 

PMID- 24931561
TI  - Prevalence of sleep disorders by sex and ethnicity among older adolescents and
      emerging adults: relations to daytime functioning, working memory and mental
      health.
AB  - The study determined the prevalence of sleep disorders by ethnicity and sex, and
      related daytime functioning, working memory, and mental health among older
      adolescent to emerging adult college students. Participants were U.S.A.
      undergraduates (N = 1684), aged 17-25, recruited from 2010 to 2011. Participants
      completed online questionnaires for all variables. Overall, 36.0% of the sample
      screened positive for sleep disorders with insomnia, restless legs syndrome, and
      periodic limb movement disorder being the most prevalent. Women reported more
      insomnia and daytime impairment. African-Americans reported more early morning
      awakenings and less daytime impairment. Students with insomnia symptoms or
      restless legs syndrome tended to have lower working memory capacities. Students
      with nightmares or parasomnias had greater odds for mental disorders. In an older
      adolescent to emerging adult college student sample, sleep disorders may be a
      common source of sleep disturbance and impairment. Certain sleep disorders may be
      associated with lower working memory capacity and poor mental health.

PMID- 24931562
TI  - Brief report: identity processes in Filipino late adolescents and young adults:
      parental influences and mental health outcomes.
AB  - This study focused on a process-oriented approach to identity formation using a
      sample of Filipino late adolescents and young adults (17-30 years; N = 779).
      Indirect relations between parenting and mental health via identity formation
      processes were examined. Two parenting dimensions (psychological control and
      support), two types of mental health outcomes (depression and psychological well
      being), and five identity dimensions (commitment making (CM), identification with
      commitment (IC), exploration in breadth (EB), exploration in depth (ED), and
      ruminative exploration (RE)) were assessed. Recursive path analysis showed
      indirect relations between parenting and mental health via EB, ED, RE, and IC.
      Model differences between late adolescents (17-21 year olds) and young adults (22
      30 year olds) were examined using multigroup path analysis. Results showed that
      the direct effect of psychological control on RE, and its indirect effect on
      depression through RE differed between the age groups. Implications and
      suggestions for future research are provided.

PMID- 24931563
TI  - The adolescent emotional coping after an earthquake: a risk factor for suicidal
      ideation.
AB  - The study aims to investigate the relationship of suicidal ideation with coping
      and resilience in a sample of adolescents who survived an earthquake. Three
      hundred forty-three adolescents who had experienced the L'Aquila earthquake were
      investigated for a screening distinguishing Suicidal Screen-Negative (SSN) from
      the Positive (SSP) subjects. Resilience Scale for Adolescents (READ) and Brief
      Cope were administered. Emotion-focused coping score was significantly higher in
      SSP subjects. In the SSN but not in the SSP sample the READ total score
      correlated with problem-focused total score. A positive correlation was seen
      between emotion-focused and problem-focused scores in both samples, with a higher
      coefficient in SSP sample. Externalising problems and maladaptive behaviours can
      arise in adolescents exposed to traumatic events. Attention should be paid in
      reducing risk factors and in the development of psychological abilities,
      improving the coping strategies that can protect from emotional despair and
      suicidal ideation. 

PMID- 24931564
TI  - Understanding the relationship between actual:ideal discrepancies and depressive
      symptoms: a developmental examination.
AB  - Self-discrepancy theory (SDT) is one framework for understanding how goal failure
      is associated with depressive symptoms. The present studies sought to examine the
      variance in depressive symptoms explained by actual:ideal discrepancies, beyond
      what is accounted for by actual-self ratings. Additionally, gender and grade were
      examined as potential moderators in the relationship. In Study 1 (N = 228),
      discrepancies accounted for additional variance in the level of depressive
      symptoms beyond what was explained by actual-self ratings in a college sample. In
      Study 2 (N = 192), while similar global patterns were found, gender and grade
      differences emerged. For boys, the relationship between actual:ideal
      discrepancies and depressive symptoms was due to actual-self ratings. For girls,
      a developmental pattern suggested that actual:ideal discrepancies become more
      important to the prediction of depressive symptoms among older girls.
      Implications for the emergence of the discrepancy-depression association are
      discussed.

PMID- 24931565
TI  - Cognitive styles in depressed children with and without comorbid conduct
      disorder.
AB  - Little is known about patterns of cognitive impairment in depression comorbid
      with conduct disorder. The study included clinically depressed children with (N =
      23) or without conduct disorder (N = 29), and controls without psychiatric
      disorder (N = 37). Cognitive biases typical of depression and patterns of social
      information processing were assessed. Both depressed groups had substantially
      higher rates of negative cognitive distortions, attributional biases and
      ruminative responses than non-depressed children. Children in the comorbid group
      made more hostile attributions and suggested more aggressive responses for
      dealing with threatening social situations, whilst children with depression only
      were more likely to be unassertive. Depression has a number of similar
      depressotypic cognitive biases whether or not complicated by conduct disorder,
      and may be potentially susceptible to similar interventions. The results also
      highlight the importance of recognising social information processing deficits
      when they occur and targeting those too, especially in comorbid presentations.

PMID- 24931566
TI  - Adolescents' expected civic participation: the role of civic knowledge and
      efficacy beliefs.
AB  - In the present study we examined the role of civic knowledge and efficacy beliefs
      as factors that can promote adolescents' expectations to participate in civic
      activities, while also taking into consideration the influences of socio-economic
      background and gender differences. Structural equation modelling techniques were
      used to examine data from the International Civic and Citizenship Study,
      collected from 3352 eighth grade Italian students. Gender was found to
      significantly moderate some relationships between the variables, while efficacy
      beliefs, rather than civic knowledge, positively influenced expected civic
      participation. Socio-economic background influenced all the variables included in
      the study, but it had a very small direct influence on adolescents' expected
      civic participation. It therefore appears that adolescents' expected civic
      participation can be encouraged by making them more confident about their civic
      and political abilities. These results extend our understanding of civic
      engagement in adolescents, and can inform policies aiming to promote it. 

PMID- 24931568
TI  - Reduced intraepidermal nerve fiber density in patients with chronic ischemic pain
      in peripheral arterial disease.
AB  - Chronic ischemic pain in peripheral arterial disease (PAD) is a leading cause of
      pain in the lower extremities. A neuropathic component of chronic ischemic pain
      has been shown independent of coexisting diabetes. We aimed to identify a
      morphological correlate potentially associated with pain and sensory deficits in
      PAD. Forty patients with symptomatic PAD (Fontaine stages II-IV), 20 with
      intermittent claudication (CI), and 20 with critical limb ischemia (CLI) were
      enrolled; 12 volunteers served as healthy controls. All patients were examined
      using pain scales and questionnaires. All study participants underwent
      quantitative sensory testing (QST) at the distal calf and skin punch biopsy at
      the distal leg for determination of intraepidermal nerve fiber density (IENFD).
      Additionally, S100 beta serum levels were measured as a potential marker for
      ischemic nerve damage. Neuropathic pain questionnaires revealed slightly higher
      scores and more pronounced pain-induced disability in CLI patients compared to CI
      patients. QST showed elevated thermal and mechanical detection pain thresholds as
      well as dynamic mechanical allodynia, particularly in patients with advanced
      disease. IENFD was reduced in PAD compared to controls (P<0.05), more pronounced
      in the CLI subgroup (CLI: 1.3 +/- 0.5 fibers/mm, CI: 2.9 +/- 0.5 fibers/mm,
      controls: 5.3 +/- 0.6 fibers/mm). In particular, increased mechanical and heat
      pain thresholds negatively correlated with lower IENFD. Mean S100 beta levels
      were in the normal range but were higher in advanced disease. Patients with
      chronic ischemic pain had a reduced IENFD associated with impaired sensory
      functions. These findings support the concept of a neuropathic component in
      ischemic pain.

PMID- 24931567
TI  - An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in
      patients with mild Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with insulin resistance and specific
      regional declines in cerebral metabolism. The effects of a novel mTOT modulating
      insulin sensitizer (MSDC-0160) were explored in non-diabetic patients with mild
      AD to determine whether treatment would impact glucose metabolism measured by FDG
      PET in regions that decline in AD. MSDC-0160 (150 mg once daily; N=16) compared
      to placebo (N=13) for 12 weeks did not result in a significant difference in
      glucose metabolism in pre-defined regions when referenced to the pons or whole
      brain. However, glucose metabolism referenced to cerebellum was maintained in
      MSDC-0160 treated participants while it significantly declined for placebo
      patients in anterior and posterior cingulate, and parietal, lateral temporal,
      medial temporal cortices. Voxel-based analyses showed additional differences in
      FDG-PET related to MSDC-0160 treatment. These exploratory results suggest central
      effects of MSDC-0160 and provide a basis for further investigation of mTOT
      modulating insulin sensitizers in AD patients. 

PMID- 24931569
TI  - What is your diagnosis? Blood smear from a cat.

PMID- 24931570
TI  - Fluorescent chemosensors for anions and contact ion pairs with a cavity-based
      selectivity.
AB  - The association of a concave macrocyclic compound to one or multiple fluorophores
      is an appealing strategy for the design of chemosensors. Indeed, as with
      biological systems, a cavity-based selectivity can be expected with such
      fluorescent receptors. Examples of calix[6]arene-based systems using this
      strategy are rare in the literature, and to our knowledge, no examples of
      fluorescent receptors that can bind organic contact ion pairs have been reported.
      This report describes the straightforward synthesis of fluorescent calix[6]arene
      based receptors 4a and 4b bearing three pyrenyl subunits and the study of their
      binding properties toward anions and ammonium salts using different
      spectroscopies. It was found that receptor 4a exhibits a remarkable selectivity
      for the sulfate anion in DMSO, enabling its selective sensing by fluorescence
      spectroscopy. In CDCl3, the receptor is able to bind ammonium ions efficiently
      only in association with the sulfate anion. Interestingly, this cooperative
      binding of ammonium sulfate salts was also evidenced in a protic environment.
      Finally, a cavity-based selectivity in terms of size and shape of the guest was
      observed with both receptors 4a and 4b, opening interesting perspectives on the
      elaboration of fluorescent cavity-based systems for the selective sensing of
      biologically relevant ammonium salts such as neurotransmitters. 

PMID- 24931571
TI  - Interruption of KLF5 acetylation converts its function from tumor suppressor to
      tumor promoter in prostate cancer cells.
AB  - KLF5 possesses both tumor suppressing and tumor promoting activities, though the
      mechanism controlling these opposing functions is unknown. In cultured
      noncancerous epithelial cells, KLF5 converts from proproliferative to
      antiproliferative activity upon TGFbeta-induced acetylation, which sequentially
      alters the KLF5 transcriptional complex and the expression of genes such as p15
      and MYC. In this study, we tested whether the acetylation status of KLF5 also
      determines its opposing functions in tumorigenesis using the PC-3 and DU 145
      prostate cancer cell lines, whose proliferation is inhibited by TGFbeta. KLF5
      inhibited the proliferation of these cancer cells, and the inhibition was
      dependent on KLF5 acetylation. MYC and p15 showed the same patterns of expression
      change found in noncancerous cells. In nude mice, KLF5 also suppressed tumor
      growth in an acetylation-dependent manner. Furthermore, deacetylation switched
      KLF5 to tumor promoting activity, and blocking TGFbeta signaling attenuated the
      tumor suppressor activity of KLF5. RNA sequencing and comprehensive data analysis
      suggest that multiple molecules, including RELA, p53, CREB1, MYC, JUN, ER, AR and
      SP1, mediate the opposing functions of AcKLF5 and unAcKLF5. These results provide
      novel insights into the mechanism by which KLF5 switches from antitumorigenic to
      protumorigenic function and also suggest the roles of AcKLF5 and unAcKLF5,
      respectively, in the tumor suppressing and tumor promoting functions of TGFbeta. 

PMID- 24931573
TI  - High-dose intravenous vancomycin therapy and the risk of nephrotoxicity.
AB  - PURPOSE: National guidelines recommend higher serum trough concentrations when
      using vancomycin to treat certain clinical conditions, but there is concern that
      higher-dose vancomycin therapy causes nephrotoxicity. We evaluated risk factors
      associated with nephrotoxicity in patients receiving high-dose intravenous
      vancomycin. METHODS: This retrospective cohort study evaluated the clinical
      outcome of 80 hospitalized adult patients with normal baseline renal function who
      received >=4 g/d of intravenous vancomycin for >=48 hours between January 1,
      2011, and December 31, 2011. After abstracting clinical risk factors, we used an
      analysis by methods of best clinical subsets to develop a multivariable model
      predicting nephrotoxicity in patients receiving high-dose vancomycin. FINDINGS:
      The overall rate of nephrotoxicity in the study population was 6%. Trough
      concentrations >20 mg/L were identified in a similar proportion of patients who
      did and did not develop nephrotoxicity. Patients who developed nephrotoxicity
      trended toward having a lower body mass index, higher daily dose, longer duration
      of therapy, and greater exposure to intravenous contrast and nephrotoxic
      medications. In a multivariable model, the combination of intravenous contrast
      and nephrotoxic medications was a significant predictor of nephrotoxicity, and
      duration of high-dose vancomycin was a significant confounder. IMPLICATIONS:
      Administration of high-dose intravenous vancomycin may have less associated
      nephrotoxicity than previously reported, although duration of vancomycin therapy
      may play a role. Concomitant exposure to intravenous contrast and other
      nephrotoxic medications is a more significant predictor of developing
      nephrotoxicity than vancomycin dose or trough.

PMID- 24931574
TI  - Perceived learning needs of rural doctors: what they want or what they need?

PMID- 24931572
TI  - Outpatient glycemic control with a bionic pancreas in type 1 diabetes.
AB  - BACKGROUND: The safety and effectiveness of automated glycemic management have
      not been tested in multiday studies under unrestricted outpatient conditions.
      METHODS: In two random-order, crossover studies with similar but distinct
      designs, we compared glycemic control with a wearable, bihormonal, automated,
      "bionic" pancreas (bionic-pancreas period) with glycemic control with an insulin
      pump (control period) for 5 days in 20 adults and 32 adolescents with type 1
      diabetes mellitus. The automatically adaptive algorithm of the bionic pancreas
      received data from a continuous glucose monitor to control subcutaneous delivery
      of insulin and glucagon. RESULTS: Among the adults, the mean plasma glucose level
      over the 5-day bionic-pancreas period was 138 mg per deciliter (7.7 mmol per
      liter), and the mean percentage of time with a low glucose level (<70 mg per
      deciliter [3.9 mmol per liter]) was 4.8%. After 1 day of automatic adaptation by
      the bionic pancreas, the mean (+/-SD) glucose level on continuous monitoring was
      lower than the mean level during the control period (133+/-13 vs. 159+/-30 mg per
      deciliter [7.4+/-0.7 vs. 8.8+/-1.7 mmol per liter], P<0.001) and the percentage
      of time with a low glucose reading was lower (4.1% vs. 7.3%, P=0.01). Among the
      adolescents, the mean plasma glucose level was also lower during the bionic
      pancreas period than during the control period (138+/-18 vs. 157+/-27 mg per
      deciliter [7.7+/-1.0 vs. 8.7+/-1.5 mmol per liter], P=0.004), but the percentage
      of time with a low plasma glucose reading was similar during the two periods
      (6.1% and 7.6%, respectively; P=0.23). The mean frequency of interventions for
      hypoglycemia among the adolescents was lower during the bionic-pancreas period
      than during the control period (one per 1.6 days vs. one per 0.8 days, P<0.001).
      CONCLUSIONS: As compared with an insulin pump, a wearable, automated, bihormonal,
      bionic pancreas improved mean glycemic levels, with less frequent hypoglycemic
      episodes, among both adults and adolescents with type 1 diabetes mellitus.
      (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases
      and others; ClinicalTrials.gov numbers, NCT01762059 and NCT01833988.).

PMID- 24931575
TI  - NiSb alloy hollow nanospheres as anode materials for rechargeable lithium ion
      batteries.
AB  - NiSb alloy hollow nanospheres (HNSs) obtained by galvanic replacement were
      firstly applied as anode materials for lithium ion batteries, giving the best
      electrochemical performances for NiSb alloy materials so far with a high
      reversible capacity of 420 mA h g(-1) after 50 cycles, close to its theoretical
      capacity (446 mA h g(-1)). 

PMID- 24931577
TI  - Intravitreal drug delivery in retinal disease: are we out of our depth?
AB  - INTRODUCTION: With the ever-increasing global burden of retinal disease, there is
      an urgent need to vastly improve formulation strategies that enhance posterior
      eye delivery of therapeutics. Despite intravitreal administration having
      demonstrated notable superiority over other routes in enhancing retinal drug
      availability, there still exist various significant physical/biochemical barriers
      preventing optimal drug delivery into the retina. A further complication lies
      with an inability to reliably translate laboratory-based retinal models into a
      clinical setting. Several formulation approaches have recently been evaluated to
      improve intravitreal therapeutic outcomes, and our aim in this review is to
      highlight strategies that hold the most promise. AREAS COVERED: We discuss the
      complex barriers faced by the intravitreal route and examine how formulation
      strategies including implants, nanoparticulate carriers, viral vectors and
      sonotherapy have been utilized to attain both sustained delivery and enhanced
      penetration through to the retina. We conclude by highlighting the advances and
      limitations of current in vitro, ex vivo and in vivo retinal models in use by
      researchers globally. EXPERT OPINION: Various nanoparticle compositions have
      demonstrated the ability to overcome the retinal barriers successfully; however,
      their utility is limited to the laboratory setting. Optimization of these
      formulations and the development of more robust experimental retinal models are
      necessary to translate success in the laboratory into clinically efficacious
      outcomes.

PMID- 24931576
TI  - Mpl traffics to the cell surface through conventional and unconventional routes.
AB  - Myeloproliferative neoplasms (MPNs) are often characterized by JAK2 or
      calreticulin (CALR) mutations, indicating aberrant trafficking in pathogenesis.
      This study focuses on Mpl trafficking and Jak2 association using two model
      systems: human erythroleukemia cells (HEL; JAK2V617F) and K562 myeloid leukemia
      cells (JAK2WT). Consistent with a putative chaperone role for Jak2, Mpl and Jak2
      associate on both intracellular and plasma membranes (shown by proximity ligation
      assay) and siRNA-mediated knockdown of Jak2 led to Mpl trapping in the
      endoplasmic reticulum (ER). Even in Jak2 sufficient cells, Mpl accumulates in
      punctate structures that partially colocalize with ER-tracker, the ER exit site
      marker (ERES) Sec31a, the autophagy marker LC3 and LAMP1. Mpl was fused to
      miniSOG, a genetically encoded tag for correlated light and electron microscopy.
      Results suggest that a fraction of Mpl is taken up into autophagic structures
      from the ER and routed to autolyososomes. Surface biotinylation shows that both
      immature and mature Mpl reach the cell surface; in K562 cells Mpl is also
      released in exosomes. Both forms rapidly internalize upon ligand addition, while
      recovery is primarily attributed to immature Mpl. Mpl appears to reach the plasma
      membrane via both conventional ER-Golgi and autolysosome secretory pathways, as
      well as recycling. 

PMID- 24931578
TI  - Impact of peri-transplant vancomycin and fluoroquinolone administration on rates
      of bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients:
      a 12-year single institution study.
AB  - BACKGROUND: We analyzed the effect of peri-transplant prophylaxis on the
      epidemiology of bacteremia in a 12-year contemporary cohort of allogeneic HSCT
      recipients at our center. METHODS: This was an observational study of 1052
      consecutive adult HSCT from 2000 to 2011. Formal prophylaxis with vancomycin
      only, fluoroquinolone (FQ) only, or vancomycin + FQ was implemented in 2006. The
      cumulative incidence of day 100 bacteremia was compared between the Early Period
      (2000-2005) and the Recent Period (2006-2011). Predictors for pre-engraftment
      bacteremia were analyzed with Cox-proportional hazard models in a subcohort of
      821 HSCT who received myeloablative or reduced intensity conditioning (MA/RIC).
      RESULTS: The incidence of bacteremia decreased in the Recent Period (32% vs 27%;
      P = 0.002), whereas the rates of resistance in gram-negative rods (GNR) and
      vancomycin-resistant enterococci (VRE) were similar between the two Periods (P
      values are not statistically significant.) In multivariate analyses, prophylaxis
      with vancomycin only or vancomycin + FQ was protective (HR = 0.5; CI = 0.30-0.72)
      and (HR = 0.3; CI = 0.12-0.52, P < 0.01). Vancomycin or vancomycin + FQ
      eliminated viridans streptococcal bacteremia (VSB); vancomycin + FQ decreased GNR
      bacteremia (HR = 0.35; CI = 0.15-0.85). CONCLUSIONS: Vancomycin-based prophylaxis
      peri-transplant in MA/RIC HSCT was associated with elimination of VSB and may be
      considered at centers with high incidence of this infection.

PMID- 24931579
TI  - No evidence for a protective effect of naturally induced HPV antibodies on
      subsequent anogenital HPV infection in HIV-negative and HIV-infected MSM.
AB  - OBJECTIVES: To assess whether HPV serum antibodies detected after natural
      infection protect against subsequent anal or penile infection with the same HPV
      type in HIV-negative and HIV-infected men who have sex with men (MSM). METHODS:
      MSM aged >=18 years were recruited in Amsterdam, the Netherlands (2010-2011), and
      followed-up semi-annually. Antibodies against 7 high-risk HPV types in baseline
      serum samples were tested using a multiplex immunoassay; baseline, 6-, and 12
      month anal and penile samples were tested for HPV DNA and genotyped using the
      SPF10-PCR DEIA/LiPA25 system (version 1). Statistical analyses were performed
      using the Wei-Lin-Weissfeld method. RESULTS: 719 MSM (median age 40 years; IQR 35
      48) with baseline and follow-up data were included in these analyses; 287 (40%)
      were HIV-infected. HPV seropositivity at baseline was not significantly
      associated with subsequent type-specific HPV infection at 6 or 12 months in
      multivariable analyses (for anal infection adjusted hazard ratio (aHR) 1.2; 95%
      CI 0.9-1.6; for penile infection aHR 0.8; 95% CI 0.6-1.2). High antibody
      concentrations showed no protective effect against subsequent infection either.
      CONCLUSIONS: In a population of highly sexually active, adult MSM, naturally
      induced HPV antibodies may not protect MSM against subsequent anal or penile HPV
      infection within one year.

PMID- 24931580
TI  - Fragility of epidermis and its consequence in dermatology.
AB  - The skin is the largest organ of the body, providing a protective barrier against
      bacteria, chemicals and physical insults while maintaining homeostasis in the
      internal environment. Such a barrier function the skin ensures protection against
      excessive water loss. The skin's immune defence consists of several facets,
      including immediate, non-specific mechanisms (innate immunity) and delayed,
      stimulus-specific responses (adaptive immunity), which contribute to fending off
      a wide range of potentially invasive microorganisms. This article is an overview
      of all known data about 'fragile skin'. Fragile skin is defined as skin with
      lower resistance to aggressions. Fragile skin can be classified into four
      categories up to its origin: physiological fragile skin (age, location),
      pathological fragile skin (acute and chronic), circumstantial fragile skin (due
      to environmental extrinsic factors or intrinsic factors such as stress) and
      iatrogenic fragile skin. This article includes the epidemiologic data, pathologic
      description of fragile skin with pathophysiological bases (mechanical and
      immunological role of skin barrier) and clinical description of fragile skin in
      atopic dermatitis, in acne, in rosacea, in psoriasis, in contact dermatitis and
      other dermatologic pathologies. This article includes also clinical cases and
      differential diagnosis of fragile skin (reactive skin) in face in adult
      population. In conclusion, fragile skin is very frequent worldwide and its
      prevalence varies between 25% and 52% in Caucasian, African and Asian population.

PMID- 24931586
TI  - An unprovoked attack by a blue shark, Prionace glauca (Chondrichthyes:
      Carcharhinidae) on a spear fisherman in Terceira Island, Azores, Northeast
      Atlantic.

PMID- 24931585
TI  - In reply to 'Spine protection in the austere environment'.

PMID- 24931587
TI  - Exercise limitation of acetazolamide at altitude (3459 m).
AB  - OBJECTIVE: To assess the effect of acetazolamide (Az) on exercise performance
      during early acclimatization to altitude. METHODS: Az (250 mg twice daily) or
      placebo was administered for 3 days in a double-blind, randomized manner followed
      by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age
      range, 18-67 years) were tested at 60% of sea-level peak power output for 15
      minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure.
      Exercise performance was measured in relation to peripheral oxygen saturations
      measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS)
      score, and perceived difficulty. RESULTS: At altitude, resting Spo2 was higher in
      the Az group compared with placebo (P < .001). The highest AMS scores were in 4
      of the placebo individuals with the lowest resting Spo2 (P < .05). During the
      exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in
      the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the
      exercise test; 4 of these 5 had the largest fall in Spo2. The perception of
      exercise difficulty was higher in the Az subjects compared with those taking the
      placebo (P < .01). There was an age relationship with exercise limitation; 4 of
      the 9 older than 50 years failed to complete the test whereas only 1 of 11
      younger than 50 years failed, and there were no failures in the 6 younger than 30
      years (P < .05). CONCLUSIONS: In this study group, and despite higher resting
      Spo2, Az may have compromised exercise at 3459 m altitude during early
      acclimatization, particularly in older subjects.

PMID- 24931588
TI  - Wilderness Medical Society practice guidelines for basic wound management in the
      austere environment.
AB  - In an effort to produce best-practice guidelines for wound management in the
      austere environment, the Wilderness Medical Society convened an expert panel
      charged with the development of evidence-based guidelines for the management of
      wounds sustained in an austere (dangerous or compromised) environment.
      Recommendations are made about several parameters related to wound management.
      These recommendations are graded based on the quality of supporting evidence and
      the balance between the benefits and risks or burdens for each parameter
      according to the methodology stipulated by the American College of Chest
      Physicians. 

PMID- 24931589
TI  - Spine protection in the austere environment.

PMID- 24931590
TI  - The impact of an ultramarathon on hormonal and biochemical parameters in men.
AB  - OBJECTIVE: To examine circulating hormonal responses in men competing in the
      Western States Endurance Run (WSER, June 23 to 24, 2012): a 161-km trail run that
      starts in Squaw Valley, CA, and concludes in Auburn, CA. METHODS: We examined 12
      men who completed the WSER. Blood samples were obtained the morning before the
      race, immediately postrace (IP), and 1 (D1) and 2 (D2) days after the conclusion
      of the WSER. The hypothalamic-pituitary-testicular (HPT) axis was assessed by
      measuring testosterone and luteinizing hormone (LH). We also examined sex hormone
      binding globulin (SHBG) and cortisol. Biochemical and muscle damage markers were
      also measured. RESULTS: Relative to prerace, there were significant (P <= .05)
      decreases in testosterone, LH, and SHBG, whereas cortisol showed a significantly
      marked elevation at IP. Testosterone, LH, SHBG, and cortisol remained
      significantly different from prerace at D1. Additionally, the testosterone to
      cortisol (T:C) ratio, a marker of anabolism, was decreased at IP and D1. Serum
      total protein, albumin, and globulin significantly decreased at IP, and remained
      decreased at D1 and D2. Bilirubin increased significantly IP and D1, whereas
      alkaline phosphatase decreased at D1 and D2. Creatine kinase, myoglobin,
      aspartate aminotransferase, and alanine aminotransferase increased at IP, and
      continued to be significantly elevated at D1 and D2. CONCLUSIONS: Training for
      and completing the WSER produced a significant suppression in the HPT axis as
      seen by decreased levels of testosterone and LH. Additionally, running the WSER
      continued to influence endocrine function until 2 days after the race.
      Furthermore, the stress caused by the WSER produced severe muscle damage.

PMID- 24931591
TI  - Sleeping in moderate hypoxia at home for prevention of acute mountain sickness
      (AMS): a placebo-controlled, randomized double-blind study.
AB  - OBJECTIVE: Acclimatization at natural altitude effectively prevents acute
      mountain sickness (AMS). It is, however, unknown whether prevention of AMS is
      also possible by only sleeping in normobaric hypoxia. METHODS: In a placebo
      controlled, double-blind study 76 healthy unacclimatized male subjects, aged 18
      to 50 years, slept for 14 consecutive nights at either a fractional inspired
      oxygen (Fio2) of 0.14 to 0.15 (average target altitude 3043 m; treatment group)
      or 0.209 (control group). Four days later, AMS scores and incidence of AMS were
      assessed during a 20-hour exposure in normobaric hypoxia at Fio2 = 0.12
      (equivalent to 4500 m). RESULTS: Because of technical problems with the nitrogen
      generators, target altitude was not achieved in the tents and only 21 of 37
      subjects slept at an average altitude considered sufficient for acclimatization
      (>2200 m; average, 2600 m). Therefore, in a subgroup analysis these subjects were
      compared with the 21 subjects of the control group with the lowest sleeping
      altitude. This analysis showed a significantly lower AMS-C score (0.38; 95% CI,
      0.21 to 0.54) vs 1.10; 95% CI, 0.57 to 1.62; P = .04) and lower Lake Louise Score
      (3.1; 95% CI, 2.2 to 4.1 vs 5.1; 95% CI, 3.6 to 6.6; P = .07) for the treatment
      subgroup. The incidence of AMS defined as an AMS-C score greater than 0.70 was
      also significantly lower (14% vs 52%; P < .01). CONCLUSIONS: Sleeping 14
      consecutive nights in normobaric hypoxia (equivalent to 2600 m) reduced symptoms
      and incidence of AMS 4 days later on exposure to 4500 m.

PMID- 24931592
TI  - A nanobody-based electrochemiluminescent immunosensor for sensitive detection of
      human procalcitonin.
AB  - The development of a nanobody-based electrochemiluminescent immunosensor for
      procalcitonin quantification is described. A highly specific and enhanced
      sensitivity of target detection was achieved by CdTe quantum dot encapsulated
      silica nanoparticle-assisted signal amplification. 

PMID- 24931593
TI  - Significance of physical performance tests for patients with low back pain.
AB  - OBJECTIVES: Several research groups established functional tests to obtain
      performance data for mobility-related activities in patients with low back pain
      (LBP). In our study we aimed to assess the construct validity and associations
      with other measures of a battery of functional tests in relationship to physical
      performance on the one hand and physical capacity and variables of pain,
      disability and psychological variables on the other. DESIGN: Eight physical
      performance tests of everyday activities such as climbing stairs, picking up an
      object from the floor, bending forward, and sitting up from supine position etc.
      were evaluated in 106 patients with LBP and 106 control subjects. RESULTS:
      Distribution of results in each test demonstrated a marked overlap in a number of
      tests between those with and those without back pain. In a factor analysis we
      found pronounced differences in the factorial structure of the data between
      patients and control subjects as well in the bivariate correlations between
      functional test results. There was a strong relationship between self-report
      disability rating (FFbH-R) and physical performance tests especially in patients
      whereas physical capacity tests had less relationship in patients and not at all
      in the control subjects. CONCLUSION: In contrast to the past and present
      literature, our results suggest that physical performance tests have an inherent
      problem to sharply differentiate patients with back pain from healthy controls
      and problems with inter-rater reliability. Physical performance seems to be more
      a matter of patients' perception of generalized disability than of restricted
      function.

PMID- 24931594
TI  - Dynamic contrast-enhanced magnetic resonance imaging: applications in oncology.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) allows functional
      characterisation of tissue perfusion characteristics and acts as a biomarker for
      tumour angiogenesis. It involves serial acquisition of MRI images before and
      after injection of contrast, as such, tissue perfusion and permeability can be
      assessed based on the signal enhancement kinetics. The ability to evaluate whole
      tumour volumes in a non-invasive manner makes DCE MRI especially attractive for
      potential oncological applications. Here we provide an overview of the current
      research involving DCE MRI as a biomarker for the diagnosis and characterisation
      of malignancies, prediction of the therapeutic response and survival outcomes, as
      well as radiation therapy planning. 

PMID- 24931595
TI  - Stress and photosynthesis.

PMID- 24931596
TI  - Contextual considerations in implementing problem-based learning approaches in a
      Brazilian medical curriculum: the UNAERP experience.
AB  - BACKGROUND: Despite being a well-established pedagogical approach in medical
      education, the implementation of problem-based learning (PBL) approaches hinges
      not only on educational aspects of the medical curriculum but also on the
      characteristics and necessities of the health system and the medical labor market
      within which it is situated. AIM: To report our experiences implementing a PBL
      based approach in a region of Brazil where: 1) all pre-university education and
      the vast majority of medical courses are based on traditional, lecture-based
      instructions; and 2) students' career interests in primary care, arguably the
      prototypical PBL trainee, are heavily disfavored because of economics. RESULTS:
      Brazilian guidelines require that clinical training take place during the last 2
      years of the medical program and include intensive, supervised, inpatient and
      outpatient rotations in pediatrics, family medicine, obstetrics and gynecology,
      internal medicine, and surgery. Throughout the pre-clinical curriculum, then,
      students learn to deal with progressively more difficult and complex cases-
      typically through the use of PBL tutors in a primary care context. However,
      because of curricular time constraints in the clerkships, and students' general
      preoccupation with specialty practice, the continuation of PBL-based approaches
      in the pre-clinical years--and the expansion of PBL into the clerkships--has
      become exceedingly difficult. DISCUSSION AND CONCLUSION: Our experience
      illustrates the importance of context (both cultural and structural) in
      implementing certain pedagogies within one Brazilian training program. We plan to
      address these barriers by: 1) integrating units, whenever possible, within a
      spiral curriculum; 2) introducing real patients earlier in students' pre-clinical
      coursework (primarily in a primary care setting); and 3) using subject experts as
      PBL tutors to better motivate students.

PMID- 24931598
TI  - Rational design and identification of a non-peptidic aggregation inhibitor of
      amyloid-beta based on a pharmacophore motif obtained from cyclo[-Lys-Leu-Val-Phe
      Phe-].
AB  - Inhibition of pathogenic protein aggregation may be an important and
      straightforward therapeutic strategy for curing amyloid diseases. Small-molecule
      aggregation inhibitors of Alzheimer's amyloid-beta (Abeta) are extremely scarce,
      however, and are mainly restricted to dye- and polyphenol-type compounds that
      lack drug-likeness. Based on the structure-activity relationship of cyclic
      Abeta16-20 (cyclo-[KLVFF]), we identified unique pharmacophore motifs comprising
      side-chains of Leu(2), Val(3), Phe(4), and Phe(5) residues without involvement of
      the backbone amide bonds to inhibit Abeta aggregation. This finding allowed us to
      design non-peptidic, small-molecule aggregation inhibitors that possess potent
      activity. These molecules are the first successful non-peptidic, small-molecule
      aggregation inhibitors of amyloids based on rational molecular design.

PMID- 24931597
TI  - Local increase in IgE and class switch recombination to IgE in nasal polyps in
      chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps is generally characterized
      by local Th2 inflammation and is categorized into two subtypes in Japan:
      eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal
      polyps in western countries) and non-eosinophilic chronic rhinosinusitis
      (characterized by Th1-dominant inflammation). OBJECTIVE: To investigate local IgE
      production and class switch recombination to IgE in these two subtypes of chronic
      rhinosinusitis with nasal polyps. METHODS: The identity of IgE-positive cells was
      determined using double-immunofluorescent staining for IgE and cell-type-specific
      molecular markers. To investigate the local class switch recombination to IgE and
      IgE synthesis in the mucosa, we performed real-time polymerase chain reaction to
      examine the mRNA expression of Th2 cytokines and class-switch-related molecules,
      including IL-4, IL-5, IL-13, epsilon germline gene transcripts, IgE mature
      transcript, IgG mature transcript, RAG1, RAG2 and activation-induced cytidine
      deaminase in eosinophilic polyps, non-eosinophilic polyps and controls. RESULTS:
      The concentrations of total IgE and number of IgE-positive cells were
      significantly higher in the eosinophilic polyps compared with control and non
      eosinophilic polyps. IgE-positive cells were predominantly mast cells in
      eosinophilic polyps and significantly correlated with the number of FcepsilonR1
      positive cells in the subepithelial layer. IL-5 and IL-13 mRNA and epsilon
      germline gene transcripts expression levels were significantly higher in
      eosinophilic polyps compared with control and non-eosinophilic polyps. In
      contrast, the number of plasma cells and the expression of IgG mature transcripts
      were increased in non-eosinophilic polyps compared with eosinophilic polyps. RAG2
      mRNA was significantly increased in both eosinophilic and non-eosinophilic polyps
      compared with control mucosa. CONCLUSION AND CLINICAL RELEVANCE: The current
      study suggests local class switching to IgE, production of IgE and IgE
      localization to the surface of mast cells in eosinophilic chronic rhinosinusitis
      in the Japanese population. The difference in the IgE-related profiles between
      eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis
      suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal
      polyps.

PMID- 24931599
TI  - A quantitative and diametral analysis of human dentinal tubules at pulp chamber
      ceiling and floor under scanning electron microscopy.
AB  - The purposes of this study are (i) to evaluate and compare the dentinal tubule
      density, tubule diameter and percentage area of dentin occupied by tubules at the
      pulp chamber ceiling and floor; and (ii) to evaluate the effects of age on the
      number and dimensions of tubule openings. Twelve intact, human mandibular third
      molars were recruited. Six teeth belonged to patients up to 30 years of age and
      six teeth belonged to patients over 50 years. Scanning electron microscopic
      evaluations were made at two different locations: the pulp chamber ceiling and
      floor. The pulp chamber ceiling presented higher tubule density (P < 0.0001) and
      greater percentage area of dentin occupied by tubule openings (P < 0.0001)
      compared to the pulp chamber floor. Also, younger age group had greater tubule
      diameter (P < 0.0001), higher tubule density (P < 0.0001) and greater percentage
      area of dentin occupied by tubule openings (P < 0.0001) compared to older age
      group. Pulp chamber ceiling presents higher tubule density and greater area of
      exposed tubules. In younger people, the pulp chamber floor presents considerably
      high tubule diameter. The number and dimensions of dentinal tubule openings
      significantly decrease with age.

PMID- 24931600
TI  - Fertility treatments, maternal intelligence, and child cognition.

PMID- 24931601
TI  - Sphingosine-1-phosphate mediates AKT/ERK maintenance of dental pulp homoeostasis.
AB  - AIM: To investigate the cell status of dental pulp cells (DPCs) in a sphingosine
      1-phosphate (S1P)-induced microinflammation environment and the possible
      mechanisms of cell homoeostasis maintenance by S1P. METHODOLOGY: Sphingosine-1
      phosphate receptor (S1PR) expression was examined in DPCs within a local S1P
      induced microinflammation model established using 1 MUmol L(-1) S1P. U0126
      [extracellular signal-regulated kinase (ERK) inhibitor], LY294002 (AKT inhibitor)
      and Y27632 (ROCK inhibitor) were used to inhibit corresponding signalling
      pathways of DPCs. CCK8 and cell cycle analysis tested cell proliferation.
      Immunofluorescence staining JC-1 detected changes of mitochondrial membrane
      potential (DeltaPsim). Tests for apoptosis and the apoptosis-related proteins Bax
      and Bcl-2 were assessed by flow cytometry and western blot analysis,
      respectively. Expressions of ERK and AKT were evaluated by western blot analysis.
      The results were analysed using the Student's t-test and the significance level
      set at P < 0.05. RESULTS: Expressions of S1PR1, S1PR2 and S1PR3 in DPCs differed
      amongst individuals. DPCs maintained self-homoeostasis in response to S1P-induced
      microinflammation via S1PRs. During this repair process, ERK, AKT and ROCK had a
      short-term complementary interaction at 60 min, but then AKT and ERK gradually
      played decisive roles after 24 h in proliferation enhancement and apoptosis
      inhibition, respectively (P > 0.05). CONCLUSIONS: The AKT-ERK balance may
      determine whether DPC homoeostasis in S1P-induced microinflammation is maintained
      by synergistic regulation of cell growth and apoptosis.

PMID- 24931602
TI  - Slit/Robo signaling regulates cell fate decisions in the intestinal stem cell
      lineage of Drosophila.
AB  - In order to maintain tissue homeostasis, cell fate decisions within stem cell
      lineages have to respond to the needs of the tissue. This coordination of lineage
      choices with regenerative demand remains poorly characterized. Here, we identify
      a signal from enteroendocrine cells (EEs) that controls lineage specification in
      the Drosophila intestine. We find that EEs secrete Slit, a ligand for the Robo2
      receptor in intestinal stem cells (ISCs) that limits ISC commitment to the
      endocrine lineage, establishing negative feedback control of EE regeneration.
      Furthermore, we show that this lineage decision is made within ISCs and requires
      induction of the transcription factor Prospero in ISCs. Our work identifies a
      function for the conserved Slit/Robo pathway in the regulation of adult stem
      cells, establishing negative feedback control of ISC lineage specification as a
      critical strategy to preserve tissue homeostasis. Our results further amend the
      current understanding of cell fate commitment within the Drosophila ISC lineage.

PMID- 24931604
TI  - A rapid genome-wide microRNA screen identifies miR-14 as a modulator of Hedgehog
      signaling.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by
      binding to sequences within the 3' UTR of mRNAs. Because miRNAs bind to short
      sequences with partial complementarity, target identification is challenging. To
      complement the existing target prediction algorithms, we devised a systematic
      "reverse approach" screening platform that allows the empirical prediction of
      miRNA-target interactions. Using Drosophila cells, we screened the 3'
      untranslated regions (3' UTRs) of the Hedgehog pathway genes against a genome
      wide miRNA library and identified both predicted and many nonpredicted miRNA
      target interactions. We demonstrate that miR-14 is essential for maintaining the
      proper level of Hedgehog signaling activity by regulating its physiological
      target, hedgehog. Furthermore, elevated levels of miR-14 suppress Hedgehog
      signaling activity by cotargeting its apparent nonphysiological targets, patched
      and smoothened. Altogether, our systematic screening platform is a powerful
      approach to identifying both physiological and apparent nonphysiological targets
      of miRNAs, which are relevant in both normal and diseased tissues.

PMID- 24931603
TI  - Translation of small open reading frames within unannotated RNA transcripts in
      Saccharomyces cerevisiae.
AB  - High-throughput gene expression analysis has revealed a plethora of previously
      undetected transcripts in eukaryotic cells. In this study, we investigate >1,100
      unannotated transcripts in yeast predicted to lack protein-coding capacity. We
      show that a majority of these RNAs are enriched on polyribosomes akin to mRNAs.
      Ribosome profiling demonstrates that many bind translocating ribosomes within
      predicted open reading frames 10-96 codons in size. We validate expression of
      peptides encoded within a subset of these RNAs and provide evidence for
      conservation among yeast species. Consistent with their translation, many of
      these transcripts are targeted for degradation by the translation-dependent
      nonsense-mediated RNA decay (NMD) pathway. We identify lncRNAs that are also
      sensitive to NMD, indicating that translation of noncoding transcripts also
      occurs in mammals. These data demonstrate transcripts considered to lack coding
      potential are bona fide protein coding and expand the proteome of yeast and
      possibly other eukaryotes.

PMID- 24931605
TI  - A conditional system to specifically link disruption of protein-coding function
      with reporter expression in mice.
AB  - Conditional gene deletion in mice has contributed immensely to our understanding
      of many biological and biomedical processes. Despite an increasing awareness of
      nonprotein-coding functional elements within protein-coding transcripts, current
      gene-targeting approaches typically involve simultaneous ablation of noncoding
      elements within targeted protein-coding genes. The potential for protein-coding
      genes to have additional noncoding functions necessitates the development of
      novel genetic tools capable of precisely interrogating individual functional
      elements. We present a strategy that couples Cre/loxP-mediated conditional gene
      disruption with faithful GFP reporter expression in mice in which Cre-mediated
      stable inversion of a splice acceptor-GFP-splice donor cassette concurrently
      disrupts protein production and creates a GFP fusion product. Importantly,
      cassette inversion maintains physiologic transcript structure, thereby ensuring
      proper microRNA-mediated regulation of the GFP reporter, as well as maintaining
      expression of nonprotein-coding elements. To test this potentially generalizable
      strategy, we generated and analyzed mice with this conditional knockin reporter
      targeted to the Hmga2 locus.

PMID- 24931606
TI  - Alpha-synuclein immunotherapy blocks uptake and templated propagation of
      misfolded alpha-synuclein and neurodegeneration.
AB  - Accumulation of misfolded alpha-synuclein (alpha-syn) into Lewy bodies (LBs) and
      Lewy neurites (LNs) is a major hallmark of Parkinson's disease (PD) and dementia
      with LBs (DLB). Recent studies showed that synthetic preformed fibrils (pffs)
      recruit endogenous alpha-syn and induce LB/LN pathology in vitro and in vivo,
      thereby implicating propagation and cell-to-cell transmission of pathological
      alpha-syn as mechanisms for the progressive spread of LBs/LNs. Here, we
      demonstrate that alpha-syn monoclonal antibodies (mAbs) reduce alpha-syn pff
      induced LB/LN formation and rescue synapse/neuron loss in primary neuronal
      cultures by preventing both pff uptake and subsequent cell-to-cell transmission
      of pathology. Moreover, intraperitoneal (i.p.) administration of mAb specific for
      misfolded alpha-syn into nontransgenic mice injected intrastriatally with alpha
      syn pffs reduces LB/LN pathology, ameliorates substantia nigra dopaminergic
      neuron loss, and improves motor impairments. We conclude that alpha-syn
      antibodies could exert therapeutic effects in PD/DLB by blocking entry of
      pathological alpha-syn and/or its propagation in neurons.

PMID- 24931607
TI  - Otx2 and Oct4 drive early enhancer activation during embryonic stem cell
      transition from naive pluripotency.
AB  - Embryonic stem cells (ESCs) are unique in that they have the capacity to
      differentiate into all of the cell types in the body. We know a lot about the
      complex transcriptional control circuits that maintain the naive pluripotent
      state under self-renewing conditions but comparatively less about how cells exit
      from this state in response to differentiation stimuli. Here, we examined the
      role of Otx2 in this process in mouse ESCs and demonstrate that it plays a
      leading role in remodeling the gene regulatory networks as cells exit from ground
      state pluripotency. Otx2 drives enhancer activation through affecting chromatin
      marks and the activity of associated genes. Mechanistically, Oct4 is required for
      Otx2 expression, and reciprocally, Otx2 is required for efficient Oct4
      recruitment to many enhancer regions. Therefore, the Oct4-Otx2 regulatory axis
      actively establishes a new regulatory chromatin landscape during the early events
      that accompany exit from ground state pluripotency.

PMID- 24931608
TI  - Rapamycin prevents the development and progression of mutant epidermal growth
      factor receptor lung tumors with the acquired resistance mutation T790M.
AB  - Lung cancer in never-smokers is an important disease often characterized by
      mutations in epidermal growth factor receptor (EGFR), yet risk reduction measures
      and effective chemopreventive strategies have not been established. We identify
      mammalian target of rapamycin (mTOR) as potentially valuable target for EGFR
      mutant lung cancer. mTOR is activated in human lung cancers with EGFR mutations,
      and this increases with acquisition of T790M mutation. In a mouse model of EGFR
      mutant lung cancer, mTOR activation is an early event. As a single agent, the
      mTOR inhibitor rapamycin prevents tumor development, prolongs overall survival,
      and improves outcomes after treatment with an irreversible EGFR tyrosine kinase
      inhibitor (TKI). These studies support clinical testing of mTOR inhibitors in
      order to prevent the development and progression of EGFR mutant lung cancers.

PMID- 24931609
TI  - NUCKS is a positive transcriptional regulator of insulin signaling.
AB  - Although much is known about the molecular players in insulin signaling, there is
      scant information about transcriptional regulation of its key components. We now
      find that NUCKS is a transcriptional regulator of the insulin signaling
      components, including the insulin receptor (IR). Knockdown of NUCKS leads to
      impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit
      decreased insulin signaling and increased body weight/fat mass along with
      impaired glucose tolerance and reduced insulin sensitivity, all of which are
      further exacerbated by a high-fat diet (HFD). Genome-wide ChIP-seq identifies
      metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is
      downregulated in individuals with a high body mass index and in HFD-fed mice, and
      conversely, its levels increase upon starvation. Altogether, NUCKS is a
      physiological regulator of energy homeostasis and glucose metabolism that works
      by regulating chromatin accessibility and RNA polymerase II recruitment to the
      promoters of IR and other insulin pathway modulators.

PMID- 24931612
TI  - MicroRNAs establish robustness and adaptability of a critical gene network to
      regulate progenitor fate decisions during cortical neurogenesis.
AB  - Over the course of cortical neurogenesis, the transition of progenitors from
      proliferation to differentiation requires a precise regulation of involved gene
      networks under varying environmental conditions. In order to identify such
      regulatory mechanisms, we analyzed microRNA (miRNA) target networks in
      progenitors during early and late stages of neurogenesis. We found that cyclin D1
      is a network hub whose expression is miRNA-dosage sensitive. Experimental
      validation revealed a feedback regulation between cyclin D1 and its regulating
      miRNAs miR-20a, miR-20b, and miR-23a. Cyclin D1 induces expression of miR-20a and
      miR-20b, whereas it represses miR-23a. Inhibition of any of these miRNAs
      increases the developmental stage-specific mean and dynamic expression range
      (variance) of cyclin D1 protein in progenitors, leading to reduced neuronal
      differentiation. Thus, miRNAs establish robustness and stage-specific
      adaptability to a critical dosage-sensitive gene network during cortical
      neurogenesis. Understanding such network regulatory mechanisms for key
      developmental events can provide insights into individual susceptibilities for
      genetically complex neuropsychiatric disorders. 

PMID- 24931610
TI  - SETD2-dependent histone H3K36 trimethylation is required for homologous
      recombination repair and genome stability.
AB  - Modulating chromatin through histone methylation orchestrates numerous cellular
      processes. SETD2-dependent trimethylation of histone H3K36 is associated with
      active transcription. Here, we define a role for H3K36 trimethylation in
      homologous recombination (HR) repair in human cells. We find that depleting SETD2
      generates a mutation signature resembling RAD51 depletion at I-SceI-induced DNA
      double-strand break (DSB) sites, with significantly increased deletions arising
      through microhomology-mediated end-joining. We establish a presynaptic role for
      SETD2 methyltransferase in HR, where it facilitates the recruitment of C-terminal
      binding protein interacting protein (CtIP) and promotes DSB resection, allowing
      Replication Protein A (RPA) and RAD51 binding to DNA damage sites. Furthermore,
      reducing H3K36me3 levels by overexpressing KDM4A/JMJD2A, an oncogene and
      H3K36me3/2 demethylase, or an H3.3K36M transgene also reduces HR repair events.
      We propose that error-free HR repair within H3K36me3-decorated transcriptionally
      active genomic regions promotes cell homeostasis. Moreover, these findings
      provide insights as to why oncogenic mutations cluster within the H3K36me3 axis.

PMID- 24931611
TI  - ADAM17-dependent c-MET-STAT3 signaling mediates resistance to MEK inhibitors in
      KRAS mutant colorectal cancer.
AB  - There are currently no approved targeted therapies for advanced KRAS mutant
      (KRASMT) colorectal cancer (CRC). Using a unique systems biology approach, we
      identified JAK1/2-dependent activation of STAT3 as the key mediator of resistance
      to MEK inhibitors in KRASMT CRC in vitro and in vivo. Further analyses identified
      acute increases in c-MET activity following treatment with MEK inhibitors in
      KRASMT CRC models, which was demonstrated to promote JAK1/2-STAT3-mediated
      resistance. Furthermore, activation of c-MET following MEK inhibition was found
      to be due to inhibition of the ERK-dependent metalloprotease ADAM17, which
      normally inhibits c-MET signaling by promoting shedding of its endogenous
      antagonist, soluble "decoy" MET. Most importantly, pharmacological blockade of
      this resistance pathway with either c-MET or JAK1/2 inhibitors synergistically
      increased MEK-inhibitor-induced apoptosis and growth inhibition in vitro and in
      vivo in KRASMT models, providing clear rationales for the clinical assessment of
      these combinations in KRASMT CRC patients.

PMID- 24931614
TI  - Benefit-risk assessment in pharmaceutical research and development.

PMID- 24931613
TI  - Synaptic control of secretory trafficking in dendrites.
AB  - Localized signaling in neuronal dendrites requires tight spatial control of
      membrane composition. Upon initial synthesis, nascent secretory cargo in
      dendrites exits the endoplasmic reticulum (ER) from local zones of ER complexity
      that are spatially coupled to post-ER compartments. Although newly synthesized
      membrane proteins can be processed locally, the mechanisms that control the
      spatial range of secretory cargo transport in dendritic segments are unknown.
      Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER
      compartments under regimes of low or increased neuronal activity. In response to
      activity blockade, post-ER carriers are highly mobile and are transported over
      long distances. Conversely, increasing synaptic activity dramatically restricts
      the spatial scale of post-ER trafficking along dendrites. This activity-induced
      confinement of secretory cargo requires site-specific phosphorylation of the
      kinesin motor KIF17 by Ca(2+)/calmodulin-dependent protein kinases (CaMK). Thus,
      the length scales of early secretory trafficking in dendrites are tuned by
      activity-dependent regulation of microtubule-dependent transport.

PMID- 24931615
TI  - Avoidance of truncated proteins from unintended ribosome binding sites within
      heterologous protein coding sequences.
AB  - Genetic sequences ported into non-native hosts for synthetic biology applications
      can gain unexpected properties. In this study, we explored sequences functioning
      as ribosome binding sites (RBSs) within protein coding DNA sequences (CDSs) that
      cause internal translation, resulting in truncated proteins. Genome-wide
      prediction of bacterial RBSs, based on biophysical calculations employed by the
      RBS calculator, suggests a selection against internal RBSs within CDSs in
      Escherichia coli, but not those in Saccharomyces cerevisiae. Based on these
      calculations, silent mutations aimed at removing internal RBSs can effectively
      reduce truncation products from internal translation. However, a solution for
      complete elimination of internal translation initiation is not always feasible
      due to constraints of available coding sequences. Fluorescence assays and Western
      blot analysis showed that in genes with internal RBSs, increasing the strength of
      the intended upstream RBS had little influence on the internal translation
      strength. Another strategy to minimize truncated products from an internal RBS is
      to increase the relative strength of the upstream RBS with a concomitant
      reduction in promoter strength to achieve the same protein expression level.
      Unfortunately, lower transcription levels result in increased noise at the single
      cell level due to stochasticity in gene expression. At the low expression regimes
      desired for many synthetic biology applications, this problem becomes
      particularly pronounced. We found that balancing promoter strengths and upstream
      RBS strengths to intermediate levels can achieve the target protein concentration
      while avoiding both excessive noise and truncated protein.

PMID- 24931617
TI  - Iron deficiency anemia--bridging the knowledge and practice gap.
AB  - Despite its high prevalence, anemia often does not receive proper clinical
      attention, and detection, evaluation, and management of iron deficiency anemia
      and iron-restricted erythropoiesis can possibly be an unmet medical need. A
      multidisciplinary panel of clinicians with expertise in anemia management
      convened and reviewed recent published data on prevalence, etiology, and health
      implications of anemia as well as current therapeutic options and available
      guidelines on management of anemia across various patient populations and made
      recommendations on the detection, diagnostic approach, and management of anemia.
      The available evidence confirms that the prevalence of anemia is high across all
      populations, especially in hospitalized patients. Anemia is associated with worse
      clinical outcomes including longer length of hospital stay, diminished quality of
      life, and increased risk of morbidity and mortality, and it is a modifiable risk
      factor of allogeneic blood transfusion with its own inherent risks. Iron
      deficiency is usually present in anemic patients. An algorithm for detection and
      management of anemia was discussed, which incorporated iron study (with primary
      emphasis on transferrin saturation), serum creatinine and glomerular filtration
      rate, and vitamin B12 and folic acid measurements. Management strategies included
      iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and
      referral as needed. 

PMID- 24931616
TI  - Nesprin-1 and nesprin-2 regulate endothelial cell shape and migration.
AB  - Nesprins are large multi-domain proteins that link the nuclear envelope to the
      cytoskeleton and nucleoskeleton. Here we show that nesprin-1 and nesprin-2 play
      important roles in regulating cell shape and migration in endothelial cells.
      Nesprin-1 or nesprin-2 depletion by RNAi increased endothelial cell spread area
      and the length of cellular protrusions, as well as stimulating stress fibre
      assembly which correlated with an increase in F-actin levels. Nuclear area was
      also increased by nesprin depletion, and localization of the inner nuclear
      membrane protein emerin to the nuclear envelope was reduced. Depletion of nesprin
      1 or nesprin-2 reduced migration of endothelial cells into a cell-free area, and
      decreased loop formation in an in vitro angiogenesis assay. Taken together, our
      results indicate that nesprin-1 and nesprin-2 both regulate nuclear and
      cytoplasmic architecture, which we propose leads to their effects on endothelial
      cell migration and angiogenic loop formation.

PMID- 24931620
TI  - Synthesis, characterization, and biological activity of poly(arginine)-derived
      cancer-targeting peptides in HepG2 liver cancer cells.
AB  - The solid-phase synthesis, structural characterization, and biological evaluation
      of a small library of cancer-targeting peptides have been determined in HepG2
      hepatoblastoma cells. These peptides are based on the highly specific Pep42
      motif, which has been shown to target the glucose-regulated protein 78 receptors
      overexpressed and exclusively localized on the cell surface of tumors. In this
      study, Pep42 was designed to contain varying lengths (3-12) of poly(arginine)
      sequences to assess their influence on peptide structure and biology. Peptides
      were effectively synthesized by 9-fluorenylmethoxycarbonyl-based solid-phase
      peptide synthesis, in which the use of a poly(ethylene glycol) resin provided
      good yields (14-46%) and crude purities >95% as analyzed by liquid chromatography
      mass spectrometry. Peptide structure and biophysical properties were investigated
      using circular dichroism spectroscopy. Interestingly, peptides displayed
      secondary structures that were contingent on solvent and length of the
      poly(arginine) sequences. Peptides exhibited helical and turn conformations,
      while retaining significant thermal stability. Structure-activity relationship
      studies conducted by flow cytometry and confocal microscopy revealed that the
      poly(arginine) derived Pep42 sequences maintained glucose-regulated protein 78
      binding on HepG2 cells while exhibiting cell translocation activity that was
      contingent on the length of the poly(arginine) strand. In single dose (0.15 mM)
      and dose-response (0-1.5 mM) cell viability assays, peptides were found to be
      nontoxic in human HepG2 liver cancer cells, illustrating their potential as safe
      cancer-targeting delivery agents.

PMID- 24931618
TI  - Paroxysmal nocturnal hemoglobinuria with copy number-neutral 6pLOH in GPI (+) but
      not in GPI (-) granulocytes.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired bone marrow disorder
      caused by expansion of a clone of hematopoietic cells lacking
      glycosylphosphatidylinositol (GPI)-anchored membrane proteins. Multiple lines of
      evidence suggest immune attack on normal hematopoietic stem cells provides a
      selective growth advantage to PNH clones. Recently, frequent loss of HLA alleles
      associated with copy number-neutral loss of heterozygosity in chromosome 6p (CN
      6pLOH) in aplastic anemia (AA) patients was reported, suggesting that AA
      hematopoiesis 'escaped' from immune attack by loss of HLA alleles. We report here
      the first case of CN-6pLOH in a Japanese PNH patient only in GPI-anchored protein
      positive (59%) granulocytes, but not in GPI-anchored protein negative (41%)
      granulocytes. CN-6pLOH resulted in loss of the alleles A*02:06-DRB1*15:01
      DQB1*06:02, which have been reported to be dominant in Japanese PNH patients. Our
      patient had maintained nearly normal blood count for several years. Our case
      supports the hypothesis that a hostile immune environment drives selection of
      resistant hematopoietic cell clones and indicates that clonal evolution may occur
      also in normal phenotype (non-PNH) cells in some cases. 

PMID- 24931621
TI  - Multivariate adaptation but no increase in competitive ability in invasive
      Geranium carolinianum L. (Geraniaceae).
AB  - Adaptive evolution can affect the successful establishment of invasive species,
      but changes in selective pressures, loss of genetic variation in relevant traits,
      and/or altered trait correlations can make adaptation difficult to predict. We
      used a common-garden experiment to assess trait correlations and patterns of
      adaptation in the invasive plant, Geranium carolinianum, sampled across 20
      populations in its native (United States) and invasive (China) ranges. We used
      multivariate QST - FST tests to determine if phenotypic differences between
      countries are attributable to adaptation. We also compared population-level
      variation within each country to assess whether local adaptation resulted in
      similar multivariate phenotypes in the United States and China. Between
      countries, most phenotypic differences are indistinguishable from genetic drift,
      although we detected a signature of adaptation to the colder, drier winters in
      China. There was no evidence for increases in invasive traits in China. Within
      countries, strong multivariate adaptation appears to be driven by latitudinal
      climatic variation in the United States, but not in China. Additionally, adaptive
      trait combinations as well as their underlying correlations differ between the
      two countries, indicating that adaptation in invasive populations does not
      parallel patterns in native populations due to differences in selection
      pressures, genetic constraints, or both. 

PMID- 24931623
TI  - Effects of sequential mixed cultures of Wickerhamomyces anomalus and
      Saccharomyces cerevisiae on apple cider fermentation.
AB  - The fermentation of cider by mixed cultures of Wickerhamomyces anomalus and
      Saccharomyces cerevisiae was carried out to study their effect on the cider
      quality. The results showed that growth of W. anomalus and S. cerevisiae was
      affected by each other during co-fermentation process. All the mixed cultures
      produced statistically the same level of ethanol as S. cerevisiae monoculture.
      The mixed fermentation could produce more variety and higher amounts of acetate
      esters, ethyl esters, higher alcohols, aldehydes, and ketones. Sensory evaluation
      demonstrated that ciders obtained from co-fermentation with W. anomalus gained
      higher scores than ciders fermented by pure S. cerevisiae, especially the co
      fermentation cultures WS3, WS4, WS6, and WS8. Only 3 days of fermentation with W.
      anomalus in sequential mixtures were enough to improve the quality of cider.
      Wickerhamomyces anomalus could be used in association with S. cerevisiae to
      improve the quality of cider. The modulation of inoculation time may provide an
      effective means of manipulating cider aroma for different characteristics. 

PMID- 24931622
TI  - Cytoreductive nephrectomy in patients with synchronous metastases from renal cell
      carcinoma: results from the International Metastatic Renal Cell Carcinoma
      Database Consortium.
AB  - BACKGROUND: The benefit of cytoreductive nephrectomy (CN) for overall survival
      (OS) is unclear in patients with synchronous metastatic renal cell carcinoma
      (mRCC) in the era of targeted therapy. OBJECTIVE: To determine OS benefit of CN
      compared with no CN in mRCC patients treated with targeted therapies. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective data from patients with synchronous mRCC
      (n=1658) from the International Metastatic Renal Cell Carcinoma Database
      Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676
      mRCC patients who did not. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS was
      compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria.
      RESULTS AND LIMITATIONS: Patients who had CN had better IMDC prognostic profiles
      versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%,
      45%, and 54%, respectively). The median OS of patients with CN versus without CN
      was 20.6 versus 9.5 mo (p<0.0001). When adjusted for IMDC criteria to correct for
      imbalances, the HR of death was 0.60 (95% confidence interval, 0.52-0.69;
      p<0.0001). Patients estimated to survive <12 mo may receive marginal benefit from
      CN. Patients who have four or more of the IMDC prognostic criteria did not
      benefit from CN. Data were collected retrospectively. CONCLUSIONS: CN is
      beneficial in synchronous mRCC patients treated with targeted therapy, even after
      adjusting for prognostic factors. Patients with estimated survival times <12 mo
      or four or more IMDC prognostic factors may not benefit from CN. This information
      may aid in patient selection as we await results from randomized controlled
      trials. PATIENT SUMMARY: We looked at the survival outcomes of metastatic renal
      cell carcinoma patients who did or did not have the primary tumor removed. We
      found that most patients benefited from tumor removal, except for those with four
      or more IMDC risk factors.

PMID- 24931624
TI  - Modulation of proteome expression by F-type lectin during viral hemorrhagic
      septicemia virus infection in fathead minnow cells.
AB  - Lectins found in fish tissues play an important role in the innate immune
      response against viral infection. A fucose-binding type lectin, RbFTL-3, from
      rock bream (Oplegnathus fasciatus) was identified using expressed sequence tag
      (EST) analysis. The expression of RbFTL-3 mRNA was higher in intestine than other
      tissues of rock bream. To determine the function of RbFTL-3, VHSV-susceptible
      fathead minnow (FHM) cells were transfected with pcDNA3.1(+) or pcDNA3.1(+)-RbFTL
      3 and further infected with VHSV. The results show that the viability of FHM
      cells transfected with pcDNA3.1(+)-RbFTL-3 is higher than that of cells
      transfected with pcDNA3.1(+) (relative cell viability: 28.9% vs 56.2%). A
      comparative proteomic analysis, performed to explore the proteins related to the
      protective effect of RbFTL-3 in the cells during VHSV infection, identified 90
      proteins differentially expressed in VHSV-infected FHM cells transfected with
      pcDNA3.1(+) or pcDNA3.1(+)-RbFTL-3. The expression of RbFTL-3 inhibits a vascular
      sorting protein (SNF8) and diminishes the loss of prothrombin, which are closely
      associated with controlling viral budding and hemorrhage in fish cells,
      respectively. Subsequent Ingenuity Pathways Analysis enabled prediction of their
      biofunctional groupings and interaction networks. The results suggest RbFTL-3
      modulates the expression of proteins related to viral budding (SNF8, CCT5 and
      TUBB) and thrombin signaling (F2) to increase the viability of VHSV infected
      cells. 

PMID- 24931625
TI  - Himasthla elongata: Implantation of rediae to the specific iteroparous long
      living host, Littorina littorea, results in the immune rejection.
AB  - All semelparous short-lived gastropods studied so far for the experimental
      transplantation of trematode parthenitae, from one specific host to another,
      showed more or less successful acceptance of implanted parasites. We implanted
      echinostomatid rediae, Himasthla elongata, to the specific iteroparous long
      living host, coenogastropod Littorina littorea. Using simple and low-invasive
      implantation techniques we have tested 680 snails injected with 75 redia
      microhemipopulations (MHP) harvested from naturally infected snails. Neither
      young nor mature rediae were able to survive in the recipient periwinkles in the
      course of 30 days post-implantation. A strong immune response from the host was
      already evident within the first week after implantation: initial inactivation of
      motile rediae with toxic humoral immune factors, following encapsulation of the
      implants and increased hemocyte counts. In contrast, rediae from the same MHPs
      showed perfect survival rates in primary in vitro axenic cultures. The failure of
      the transplantation experiments is explained in terms of the compatibility
      matching phenotype model. In the studied host-parasite combination all
      periwinkles are potentially susceptible and all rediae MHPs are potentially
      infective, however the probability of the compatible phenotypes matching is
      virtually low. Low investment in L. littorea annual reproduction would result in
      increased investment in self maintenance and immune mechanisms, causing the
      general resistance to the trematode infestation. Presumably, this resistance is
      relatively higher in long-lived iteroparous gastropods compare to semelparous
      short-lived mollusks such as pulmonates.

PMID- 24931626
TI  - In vitro antibacterial analysis of phenoloxidase reaction products from the sea
      cucumber Apostichopus japonicus.
AB  - Three phenoloxidases (POs) of Apostichopus japonicus, AjPOs (AjPO1, AjPO2 and
      AjPO3), were partially purified from the coelomocytes with an electrophoretic
      method, and then employed for the in vitro antibacterial analysis. Using L-3,4
      dihydroxyphenylalanine (L-DOPA) as a substrate, AjPO1 and AjPO2-derived compounds
      inhibited the growth of Vibrio splendidus and Staphylococcus aureus, while AjPO3
      derived compounds only inhibited the growth of V. splendidus. When dopamine was
      used as a substrate, AjPO1 and AjPO3-derived compounds inhibited the growth of V.
      splendidus and Vibrio harveyi, while AjPO2-derived compounds only inhibited the
      growth of V. splendidus. Moreover, AjPO1-derived compounds showed stronger
      inhibition in V. harveyi than AjPO3-derived compounds did. However, all of the
      three AjPO reaction products showed no inhibitions on the growth of
      Pseudoalteromonas nigrifaciens, Shewanella baltica, Micrococcus lysodeikticus,
      Streptococcus dysgalactiae and Nocardiopsis sp. with L-DOPA or dopamine as a
      substrate. Scanning electron microscope (SEM) observation of V. harveyi treated
      by AjPOs and dopamine showed that AjPO1-derived compounds resulted in massive
      bacteriolysis, AjPO2-derived compounds caused no obvious alteration on bacterial
      morphology, and AjPO3-derived compounds increased the ratio of spheroidal
      bacteria. All these results suggested that AjPO reaction products derived by L
      DOPA and dopamine had different but limited antibacterial spectrum, and the
      different antibacterial effects observed among three AjPOs resulted from the
      different reaction products generated by AjPOs with the same substrate.

PMID- 24931627
TI  - Controlled production of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)
      nanoparticles for targeted and sustained drug delivery.
AB  - The ability to control the size and quality of nanoparticles (NPs) during
      production is critical for their success as a commercial product for clinical
      applications. Here, we employed a statistical design of experiment approach to
      identify the key process variables affecting the size of poly(3-hydroxybutyrate
      co-3-hydroxyhexanoate) (PHBHHx) NPs during production via the solvent evaporation
      method. The number of sonication cycles had a standardzed effect on NP size of
      55, with sonication power at 25, and PHBHHx concentration at 27 with a
      combination of these variables having a lower yet significant effect on NP size
      (p < 0.05). The PHBHHx NPs were stable for at least 7 days with an average
      polydispersity index of 0.18, a zeta potential of -10 to -40 mV, and an
      encapsulation efficiency of 63.5 +/- 2%. These data were utilized to produce a
      prediction graph whereby particles could be produced with sizes ranging from 90
      to 205 nm with a low mean curve prediction error of 1.96% for Haperzine-A-loaded
      NPs. Furthermore, a range of drug encapsulates NPs were produced and showed a
      sustained release of the encapsulated drug. This study demonstrates the ability
      to control the size of drug-loaded particles by manipulation of the production
      variables, which will allow targeted and controlled drug release to fit a variety
      of applications.

PMID- 24931628
TI  - Endoscopic single-handed septoplasty with batten graft for caudal septum
      deviation.
AB  - OBJECTIVE: Septoplasty is usually performed with a Killian incision in Japan.
      However, the major drawback of the Killian incision is the inability to correct
      deviations of the caudal part of the septum. For patients with mild deviation of
      the caudal part of the septum but with a straight caudal end, we performed a
      modified Killian incision and used a batten graft to correct the deviated
      cartilage under endoscopy. The aim of this study was to evaluate the usefulness
      of our surgical technique for these cases. METHODS: We prospectively collected
      data of 17 patients who underwent endoscopic septoplasty with a batten graft.
      Objective assessment by computed tomography and subjective assessment by
      questionnaire were performed before and 3 months after the surgery. RESULTS: On
      computed tomography, the ratio of the area of the convex side to that of the
      concave side in the anterior portion of the nasal cavity was significantly
      improved after surgery (p<0.001). Subjective assessment revealed a significant
      improvement in nasal obstruction (p=0.002). There were no complications in this
      study. CONCLUSION: The herein-described septoplasty with a batten graft is
      technically easy and considered to be useful for deviation of the caudal part of
      the septum in selected cases.

PMID- 24931629
TI  - Topical morphine gel for pain management in head and neck cancer patients.
AB  - Pain is common in head and neck cancer patients. Regardless of the cause, pain
      management is essential in supportive care. Recent research has suggested that
      opioid receptors on peripheral nerve terminals may play an important role in pain
      modulation. A number of publications have reported the use of topical morphine
      for painful ulcers that occur because of a variety of medical conditions. To the
      best of our knowledge, there are no reports in the literature regarding the use
      of morphine gel in head and neck cancer patients. We present two cases treated
      with morphine gel therapy for cutaneous pain resulting from radiation-induced
      dermatitis and tumor infiltration. We obtained good pain control in both cases
      without side effects. In one case, the use of the gel allowed a decrease in
      systemic opioid medication, and adverse effects of systemic opioid administration
      were resolved. Our experience suggests that this treatment presents great
      potential for selected head and neck cancer patients, especially those with
      prominent pain limited to the body surface. 

PMID- 24931630
TI  - Photodynamic therapy (PDT) resistance by PARP1 regulation on PDT-induced
      apoptosis with autophagy in head and neck cancer cells.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an anticancer treatment that generates
      excessive reactive oxygen species after photosensitizer treatments following
      specific wavelength irradiation. In another reports, PDT was regulated with
      autophagic cell death and apoptotic cell death. However, the mechanism of PDT
      resistance in PDT-stimulated cell death is unclear. In this study, we determined
      PDT resistance by autophagy and apoptosis in HP-PDT-treated oral cancer cells.
      MATERIALS & METHODS: Cells were treated hematoporphyrin and then irradiation with
      or without inhibitor. Cell lysates were checked protein expression with specific
      antibody. PDT resistance cells were generated with PDT repeated treatments.
      RESULTS: In HP-PDT, PDT induced autophagy through mTOR, ATG5, and LC3 in dose
      dependent manners. Also, PDT at high dose induced apoptosis through caspase
      activation and PARP-1. Moreover, PARP-1 inhibitor protected cells against HP-PDT
      induced cell death, but not by caspase inhibitor. At low dose of HP, autophagy
      inhibitor partially protected from HP-PDT-induced cell death. In autophagy
      phases, at low doses, HP-PDT regulated autophagic cell death through the
      inhibition of LC3II. Although autophagy inhibitor did not alter cell death
      directly, autophagy has associated with HP-PDT-induced apoptotic cell death by
      PARP-1 regulation. CONCLUSION: Taken together, HP-PDT induces apoptotic cell
      death with autophagy in oral cancer cells. PDT resistance is related to autophagy
      by PARP-1 regulation in oral cancer cells.

PMID- 24931631
TI  - The spectrum of somatic mutations in high-risk acute myeloid leukaemia with 
      7/del(7q).
AB  - -7/del(7q) occurs in half of myeloid malignancies with adverse-risk cytogenetic
      features and is associated with poor survival. We identified the spectrum of
      mutations that co-occur with -7/del(7q) in 40 patients with de novo or therapy
      related myeloid neoplasms. -7/del(7q) leukaemias have a distinct mutational
      profile characterized by low frequencies of alterations in genes encoding
      transcription factors, cohesin and DNA-methylation-related proteins. In contrast,
      RAS pathway activating mutations occurred in 50% of cases, a significantly higher
      frequency than other acute myeloid leukaemias and higher than previously
      reported. Our data provide guidance for which pathways may be most relevant in
      the treatment of adverse-risk myeloid leukaemia. 

PMID- 24931632
TI  - Bulk metallic glass composite with good tensile ductility, high strength and
      large elastic strain limit.
AB  - Bulk metallic glasses exhibit high strength and large elastic strain limit but
      have no tensile ductility. However, bulk metallic glass composites reinforced by
      in-situ dendrites possess significantly improved toughness but at the expense of
      high strength and large elastic strain limit. Here, we report a bulk metallic
      glass composite with strong strain-hardening capability and large elastic strain
      limit. It was found that, by plastic predeformation, the bulk metallic glass
      composite can exhibit both a large elastic strain limit and high strength under
      tension. These unique elastic mechanical properties are attributed to the
      reversible B2<->B19' phase transformation and the plastic-predeformation-induced
      complicated stress state in the metallic glass matrix and the second phase. These
      findings are significant for the design and application of bulk metallic glass
      composites with excellent mechanical properties. 

PMID- 24931633
TI  - Excited state proton transfer dynamics of an eminent anticancer drug,
      ellipticine, in octyl glucoside micelle.
AB  - Photophysics and proton transfer dynamics of an eminent anticancer drug,
      ellipticine (EPT), have been investigated inside a biocompatible octyl-beta-D
      glucoside (OBG) micellar medium using steady state and time-resolved fluorescence
      spectroscopic techniques. EPT exists as protonated form in aqueous solution of pH
      7. When EPT molecules are encapsulated in OBG micelles, protonated form is
      converted to neutral form in the ground state due to the hydrophobic effect of
      the micellar environment. Interestingly, steady state fluorescence results
      indicate the existence of both neutral and protonated forms of EPT in the excited
      state, even though neutral molecules are selectively excited, and it is
      attributed to the conversion of neutral to protonated form of EPT by the excited
      state proton transfer (ESPT) process. A clear isoemissive point in the time
      resolved area normalized emission spectra (TRANES) further supports the excited
      state conversion of neutral to protonated form of EPT. Notably, this kind of
      proton transfer dynamics is not observed in other conventional micelles, such as,
      SDS, Triton-X and CTAB. Therefore, the observed ESPT dynamics is believed to be
      an outcome of combined effects of the local dielectric constant felt by EPT and
      the local proton concentration at the OBG micellar surface.

PMID- 24931634
TI  - Adenosine-insensitive right ventricular tachycardia: novel variant of idiopathic
      outflow tract tachycardia.
AB  - BACKGROUND: A hallmark of idiopathic right ventricular outflow tract (RVOT)
      tachycardia is its sensitivity to adenosine (ADO), which is consistent with a
      triggered mechanism. We have identified a novel group of patients with ADO
      insensitive, non-reentrant RVOT tachycardia. OBJECTIVE: This study aimed to
      identify the clinical and electrophysiologic characteristics of ADO-insensitive
      RVOT tachycardia. METHODS: The response of ventricular tachycardia (VT) to ADO
      was evaluated in 46 consecutive patients with inducible sustained idiopathic RVOT
      tachycardia. The clinical and electrophysiologic characteristics of patients with
      ADO-insensitive RVOT tachycardia were compared with patients with ADO-sensitive
      VT and arrhythmogenic right ventricular cardiomyopathy (ARVC) VT. RESULTS:
      Sustained RVOT tachycardia terminated with ADO in 41 patients (89%), while 5
      patients (11%) had ADO-insensitive VT. The electrophysiology study findings of
      patients with ADO-sensitive and ADO-insensitive RVOT tachycardia were similar.
      Compared with a group of 10 patients with ARVC, patients with ADO-insensitive
      RVOT tachycardia had no ARVC-associated electrocardiographic or right ventricular
      morphologic findings, as well as fewer inducible VT morphologies. Analysis of
      myocardial biopsies at VT origin sites from 3 of 5 patients with ADO-insensitive
      RVOT tachycardia demonstrated somatic mutations in the A1 ADO receptor (R296C) in
      1 patient and in the inhibitory G protein (F200L) in another patient, as
      described previously. These mutations were not identified at remote myocardial
      sites. Over a median follow-up period of 4.8 years, no patients insensitive to
      ADO developed an ARVC phenotype. CONCLUSION: Although most forms of idiopathic
      RVOT tachycardia are characterized by ADO sensitivity, we described a variant of
      ADO-insensitive VT that, in some cases, can be linked to somatic myocardial
      mutations involving the A1 ADO receptor-associated cyclic adenosine monophosphate
      mediated pathway.

PMID- 24931635
TI  - Catastrophic failure of Durata ICD lead due to high-voltage short during shock
      delivery.

PMID- 24931636
TI  - Magnetic resonance post-contrast T1 mapping in the human atrium: validation and
      impact on clinical outcome after catheter ablation for atrial fibrillation.
AB  - BACKGROUND: The impact of diffuse atrial fibrosis detected by T1 mapping on the
      clinical outcome after atrial fibrillation (AF) ablation is unknown. OBJECTIVE:
      This study aimed to validate and assess the impact of post-contrast cardiac
      magnetic resonance (CMR) imaging atrial T1 mapping on the clinical outcome after
      catheter ablation for AF. METHODS: CMR imaging was performed in 3 groups by using
      a clinical 1.5-T scanner: controls, patients with paroxysmal AF, and patients
      with persistent AF. A T1 mapping sequence was used to calculate the post-contrast
      T1 relaxation time (T1 time) at the interatrial septum as an index of diffuse
      atrial fibrosis. A subset underwent left atrial endocardial bipolar voltage
      mapping for electrophysiologic correlation. After AF ablation, patients underwent
      clinical review and 7-day Holter monitoring at 6-month intervals. RESULTS: One
      hundred thirty-two patients (20 controls, 71 (63%) patients with paroxysmal AF,
      and 41 (37%) patients with persistent AF) underwent CMR imaging. Post-contrast
      atrial T1 time was significantly shorter in AF groups (237 +/- 42 ms) than in
      controls (280 +/- 37 ms) (P < .001). Post-contrast atrial T1 time correlated with
      mean septal voltage (R2 = .48; P < .001) and global left atrial voltage (R(2) =
      .41; P < .001). A diagnosis of AF, AF duration, and left ventricular end
      diastolic volume independently predicted shortened post-contrast atrial T1 time.
      The single procedure success rate was 74% at 12 +/- 5 months postablation. Post
      contrast atrial T1 time was the only predictor of arrhythmia recurrence in
      multivariate analysis (P = .015). A post-contrast atrial T1 time of >230 ms was
      associated with freedom from AF in 85% relative to 62% with a post-contrast
      atrial T1 time of <230 ms (P = .01). CONCLUSION: Post-contrast atrial T1 time as
      measured using CMR imaging provides an index of atrial fibrosis that correlates
      with tissue voltage, presence of AF, and clinical outcomes after catheter
      ablation.

PMID- 24931637
TI  - Congenital long QT syndrome and concomitant early repolarization pattern: a
      benign association or an ICD-worthy one?

PMID- 24931638
TI  - Different characteristics and electrophysiological properties between early and
      late recurrences after acute successful catheter ablation of idiopathic right
      ventricular outflow tract arrhythmias during long-term follow-up.
AB  - BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective therapeutic
      strategy in eliminating drug-refractory idiopathic right ventricular outflow
      tract ventricular arrhythmias (RVOT VAs). It remains unclear what factors affect
      early and late VA recurrences after ablation. OBJECTIVE: The aim of our study was
      to elucidate the differences between early and late recurrences after acute
      successful RFCA of RVOT VAs in a long-term follow-up. METHODS: A total of 220
      patients with acute successful RFCA of RVOT VAs were enrolled. Detailed clinical
      characteristics and assessments by noninvasive and invasive electrophysiology
      study were explored to predict the overall, early (<=1 year), and late VA (>1
      year) recurrences. RESULTS: During a mean follow-up of 34.15 +/- 33.74 months, 45
      of 220 patients (20.5%) documented recurrence of RVOT VAs after the initial RFCA.
      Of these patients, 26 patients (57.8%) with recurrent VAs showed similar
      morphology, and 19 (42.2%) were different. Patients with recurrent VAs were
      associated with a higher incidence of hypertension, higher systolic blood
      pressure, identification of foci by pace mapping alone, shorter earliest
      activation time, more radiofrequency pulses required, and VA originating from the
      anterior free wall. Multivariate analysis demonstrated that mapping strategy and
      shorter earliest activation time preceding VA were associated with early
      recurrences (hazard ratio [HR] 2.26; 95% confidence interval [CI] 1.49-3.42; P <
      .001; and HR 0.91; 95% CI 0.85-0.98; P = .008, respectively), whereas
      hypertension was associated with late recurrence (HR 3.48; 95% CI 1.34-9.07; P =
      .001). CONCLUSION: RFCA is an effective strategy in the elimination of RVOT VAs.
      However, early and late recurrences occur commonly. Patients with early and late
      VA recurrences demonstrated nonuniform patterns of clinical characteristics and
      electrophysiological properties.

PMID- 24931639
TI  - Increased primary health care use in the first year after colorectal cancer
      diagnosis.
AB  - OBJECTIVE: The view that the general practitioner (GP) should be more involved
      during the curative treatment of cancer is gaining support. This study aimed to
      assess the current role of the GP during treatment of patients with colorectal
      cancer (CRC). DESIGN: Historical prospective study, using primary care data from
      two cohorts. SETTING: Registration Network Groningen (RNG) consisting of 18 GPs
      in three group practices with a dynamic population of about 30,000 patients.
      SUBJECTS: Patients who underwent curative treatment for CRC (n = 124) and matched
      primary care patients without CRC (reference population; n = 358). MAIN OUTCOME
      MEASURES: Primary healthcare use in the period 1998-2009. FINDINGS: Patients with
      CRC had higher primary healthcare use in the year after diagnosis compared with
      the reference population. After correction for age, gender, and consultation
      behaviour, CRC patients had 54% (range 23-92%) more face-to-face contacts, 68%
      (range 36-108%) more drug prescriptions, and 35% (range -4-90%) more referrals
      compared with reference patients. Patients consulted their GP more often for
      reasons related to anaemia, abdominal pain, constipation, skin problems, and
      urinary infections. GPs also prescribed more acid reflux drugs, laxatives, anti
      anaemic preparations, analgesics, and psycholeptics for CRC patients.
      CONCLUSIONS: The GP plays a significant role in the year after CRC diagnosis.
      This role may be associated with treatment-related side effects and psychological
      problems. Formal guidelines on the involvement of the GP during CRC treatment
      might ensure more effective allocation and communication of care between primary
      and secondary healthcare services.

PMID- 24931641
TI  - Is medicine a profession or a business?

PMID- 24931640
TI  - Acute and probable chronic Q fever during anti-TNFalpha and anti B-cell
      immunotherapy: a case report.
AB  - BACKGROUND: Q fever is caused by the intracellular bacterium Coxiella burnetii.
      Initial infection can present as acute Q fever, while a minority of infected
      individuals develops chronic Q fever endocarditis or vascular infection months to
      years after initial infection. Serology is an important diagnostic tool for both
      acute and chronic Q fever. However, since immunosuppressive drugs may hamper the
      humoral immune response, diagnosis of Q fever might be blurred when these drugs
      are used. CASE PRESENTATION: A 71-year-old Caucasian male was diagnosed with
      symptomatic acute Q fever (based on positive C. burnetii PCR followed by
      seroconversion) while using anti-tumor necrosis factor-alpha (anti-TNFalpha)
      drugs for rheumatoid arthritis (RA). He was treated for two weeks with
      moxifloxacin. After 24 months of follow-up, the diagnosis of probable chronic Q
      fever was established based on increasing anti-C. burnetii phase I IgG antibody
      titres in a immunocompromised patient combined with clinical suspicion of
      endocarditis. At the time of chronic Q fever diagnosis, he had been treated with
      anti B-cell therapy for 16 months. Antibiotic therapy consisting of 1.5 years
      doxycycline and hydroxychloroquine was started and successfully completed and no
      signs of relapse were seen after more than one year of follow-up. CONCLUSION: The
      use of anti-TNFalpha agents for RA in the acute phase of Q fever did not hamper
      the C. burnetii-specific serological response as measured by immunofluorescence
      assay. However, in the presented case, an intact humoral response did not prevent
      progression to probable chronic C. burnetii infection, most likely because
      essential cellular immune responses were suppressed during the acute phase of the
      infection. Despite the start of anti-B-cell therapy with rituximab after the
      acute Q fever episode, an increase in anti-C. burnetii phase I IgG antibodies was
      observed, supporting the notion that C. burnetii specific CD20-negative memory B
      cells are responsible for this rise in antibody titres.

PMID- 24931642
TI  - Treatment of facial telangiectasia with a small spot of intense pulsed light: a
      case series of three patients.
AB  - Intense pulsed light (IPL) technology has long been used in the treatment of
      facial telangiectasia. While the large spot size of traditional IPL devices
      offers rapid coverage, it has limitations in terms of visibility and uniform
      contact with the skin in contoured areas of the face. The novel IPL used in this
      study had a small spot size (6.35 mm) and shorter wavelength (500-635 nm),
      allowing the use of high fluence without burning the normal epidermal tissue
      surrounding the lesion, thus providing better efficacy. Treatment of facial
      telangiectasia using small-spot IPL is effective with a low risk of
      dermatological damage, and its uses for medical care are expected to diversify. 

PMID- 24931643
TI  - Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like
      breast cancer and are potential targets in tumor-associated inflammation.
AB  - Inflammation is an important component of various cancers and its inflammatory
      cells and mediators have been shown to have prognostic potential. Tumor
      infiltrating mast cells can promote tumor growth and angiogenesis, but the
      mechanism of mast cell activation is unclear. In earlier studies, we demonstrated
      that immunoglobulin free light chains (FLC) can trigger mast cells in an antigen
      specific manner. Increased expression of FLC was observed within stroma of
      various human cancers including those of breast, colon, lung, pancreas, kidney
      and skin, and FLC expression co-localized with areas of mast cell infiltration.
      In a large cohort of breast cancer patients, FLC expression was shown associated
      with basal-like cancers with an aggressive phenotype. Moreover, lambda FLC was
      found expressed in areas of inflammatory infiltration and its expression was
      significantly associated with poor clinical outcome. Functional importance of
      FLCs was shown in a murine B16F10 melanoma model, where inhibition of FLC
      mediated mast cell activation strongly reduced tumor growth. Collectively, this
      study identifies FLCs as a ligand in the pro-tumorigenic activation of mast
      cells. Blocking this pathway may open new avenues for the inhibition of tumor
      growth, while immunohistochemical staining of FLC may be helpful in the diagnosis
      and prognosis of cancer.

PMID- 24931644
TI  - The use of a plastic guide improves the safety and reduces the duration of
      endotracheal intubation in the pig.
AB  - The successful endotracheal intubation of pigs using the standard orotracheal
      method is challenging and technically difficult, because of the pig's oral
      anatomy and the presence of excess tissue in the oropharyngeal region. Hence, the
      operator, who is usually an anesthetist, requires extensive training in order to
      successfully perform the procedure in pigs. In this report, we describe a safe
      and quick method of successful endotracheal intubation in the pig using an 80-cm
      blunt-tipped plastic vascular catheter, when the pig is placed in ventral
      recumbency. Specifically, the use of this plastic guide wire shortened the
      duration of the procedure and reduced the risks of the procedure. Since the use
      of the guide wire also improves the ease of the procedure, its use will also
      enable inexperienced operators to perform successful first-time endotracheal
      intubation of pigs without causing injury. 

PMID- 24931645
TI  - Preliminary study characterizing the use of sitagliptin for glycemic control in
      healthy Beagle dogs with normal gluco-homeostasis.
AB  - Sitagliptin is a dipeptidyl peptidase-4 inhibitor aimed at treating Type 2
      diabetes mellitus (T2DM) and T1DM, by increasing blood levels of Glucagon-like
      peptide 1 (GLP-1) and insulin. The objective of this preliminary study is to
      characterize Sitagliptin's ability for glycemic control, in healthy dogs under an
      oral glucose tolerance test (OGTT) environment. Overall, Sitagliptin did not
      result in any significant changes to temporal glucose and insulin concentrations.
      However, a ~55% increase in median total GLP-1 AUC0-120 min was observed, as
      compared to baseline control in healthy dogs (n=5), thus indicating a similar
      mode of action of Sitagliptin between healthy dogs and humans. Future studies to
      validate the use of Sitagliptin with dogs suffering from insulin independent
      diabetes are warranted.

PMID- 24931646
TI  - The relationship between clinicopathological features and expression of
      epithelial and mesenchymal markers in spontaneous canine mammary gland tumors.
AB  - It is known that epithelial mesenchymal transition (EMT) contributes to the
      acquisition of malignant property in human cancers. However, the role of EMT in
      canine tumors remains to be elucidated. To evaluate the correlation between
      expression levels of protein markers involved in EMT and clinicopathological
      characteristics in canine mammary gland tumors, immunohistochemistry using
      antibodies against ZO-1, E-cadherin, vimentin, N-cadherin and fibronectin was
      performed on 119 clinical tissue samples. Consequently, loss of ZO-1 and E
      cadherin, and gain of vimentin and N-cadherin were more frequently observed in
      malignant tumors than in benign tumors. However, there was no correlation among
      expression of these molecules. Univariate and multivariate analysis identified
      that loss of E-cadherin independently had a low one-year survival rate (adjusted
      odds ratio: 2.3, P=0.02). These results suggested that EMT might relate to
      acquisition of malignancy, and additionally, E-cadherin was strongly correlated
      with malignant behavior in canine mammary gland tumors. 

PMID- 24931649
TI  - PIV and CFD studies on analyzing intragastric flow phenomena induced by
      peristalsis using a human gastric flow simulator.
AB  - This study quantitatively analyzed the flow phenomena in model gastric contents
      induced by peristalsis using a human gastric flow simulator (GFS). Major
      functions of the GFS include gastric peristalsis simulation by controlled
      deformation of rubber walls and direct observation of inner flow through parallel
      transparent windows. For liquid gastric contents (water and starch syrup
      solutions), retropulsive flow against the direction of peristalsis was observed
      using both particle image velocimetry (PIV) and computational fluid dynamics
      (CFD). The maximum flow velocity was obtained in the region occluded by
      peristalsis. The maximum value was 9 mm s(-1) when the standard value of
      peristalsis speed in healthy adults (UACW = 2.5 mm s(-1)) was applied. The
      intragastric flow-field was laminar with the maximum Reynolds number (Re = 125).
      The viscosity of liquid gastric contents hardly affected the maximum flow
      velocity in the applied range of this study (1 to 100 mPa s). These PIV results
      agreed well with the CFD results. The maximum shear rate in the liquid gastric
      contents was below 20 s(-1) at UACW = 2.5 mm s(-1). We also measured the flow
      field in solid-liquid gastric contents containing model solid food particles
      (plastic beads). The direction of velocity vectors was influenced by the presence
      of the model solid food particle surface. The maximum flow velocity near the
      model solid food particles ranged from 8 to 10 mm s(-1) at UACW = 2.5 mm s(-1).
      The maximum shear rate around the model solid food particles was low, with a
      value of up to 20 s(-1). 

PMID- 24931648
TI  - QRS, ST and T changes of acute transmural myocardial ischemia: overview
      editorial.

PMID- 24931647
TI  - Levamisole enhances immunity in ducklings vaccinated against Riemerella
      anatipestifer.
AB  - Oil-adjuvant-inactivated vaccine is one of the most cost-effective vaccines used
      to protect ducklings against RA infection; however, it does not provide complete
      protection in very young ducklings with immature immune systems. In the current
      study, LMS was used as an immunopotentiator to improve the immune system in
      ducklings. Serum immunoglobulin (Ig)G titers and the secretions of both Th1-type
      (IFN-gamma and IL-2) and Th2-type (IL-4 and IL-10) cytokines were higher in
      ducklings that had been vaccinated with LMS. In addition, a significantly higher
      T-lymphocyte proliferation rate was obtained with the addition of LMS.
      Furthermore, all of the ducklings vaccinated with LMS were protected against RA
      on the 9th day post-vaccination, whereas only 69.2% of the ducklings were
      protected in the group that did not receive LMS. These results suggest that LMS
      might be a useful adjuvant to enhance the immune response of ducklings. The use
      of LMS may also alleviate local injection lesions, caused by the oil-emulsion
      vaccine, by reducing the dose of the vaccine. 

PMID- 24931651
TI  - A unified picture of adsorption on transition metals through different atoms.
AB  - A key issue in catalyst design is understanding how adsorption energies of
      surface intermediates vary across both different surfaces and various types of
      adsorbing atoms. In this work, we examine trends in adsorption energies of a wide
      variety of adsorbates that attach to transition metal surfaces through different
      atoms (H, C, N, O, F, S, etc.). All adsorption energies, as calculated by density
      functional theory, have nearly identical dependence on the metal bands (the d
      band center and the number of p electrons) and the adsorbates' highest occupied
      molecular orbital (HOMO) energies. However, the dependence on the adsorbate
      surface coupling and the d-band filling varies with the energy of the HOMO.
      Adsorbates with low HOMOs experience a higher level of Pauli repulsion than those
      with higher HOMOs. This leads to a classification of adsorbates into two groups,
      where adsorption energies in each group correlate. Even across the groups,
      adsorbates with similar HOMO energies are likely to have correlated adsorption
      energies. 

PMID- 24931650
TI  - Bilateral papillomacular retinoschisis and macular detachment accompanied by
      focal lamina cribrosa defect in glaucomatous eyes.
AB  - PURPOSE: We report here a patient with bilateral papillomacular retinoschisis
      with an enlarged glaucomatous optic nerve head cup and a focal lamina cribrosa
      defect, the findings of our clinical investigations of this case, and the chosen
      treatment and outcome. DESIGN: This is an observational case report. METHODS:
      Clinical examinations were performed using simultaneous confocal scanning laser
      ophthalmoscopy and optical coherence tomography (OCT). The patient was treated by
      pars plana vitrectomy (PPV). RESULTS: The left eye had a macular detachment with
      a presumed acquired pit of the optic nerve, while the right eye did not have an
      obvious optic nerve pit. Enhanced depth imaging OCT showed focal lamina cribrosa
      defects in both eyes. PPV was performed on the left eye, which resulted in a re
      attachment of the macula and improvement of the visual acuity. CONCLUSIONS: Our
      findings suggest that the pathological changes were most likely due to focal
      lamina cribrosa defects in both glaucomatous eyes. This type of maculopathy can
      be successfully treated with PPV.

PMID- 24931652
TI  - Learning style impact on knowledge gains in human patient simulation.
AB  - INTRODUCTION: Human patient simulation (HPS) is a widely used method of teaching
      in nursing education. While it is believed that a student's learning style
      impacts knowledge gains in HPS, there is little evidence to support this. This
      study sought to determine the impact of learning style on knowledge gains after a
      heart failure (HF) simulation experience in pre-licensure nursing students.
      METHODS: A convenience sample of four cohorts of prelicensure nursing students
      (n=161) were recruited from three Baccalaureate Schools of Nursing at the same
      point in their curriculum (age 25.7+/-6.6 years; gender=85.5% female) and
      participated in HPS using a HF simulation on a high-fidelity manikin. Learning
      style was assessed by the Kolb Learning Style Inventory (LSI) and pre- and post
      HPS knowledge measured by parallel, validated, knowledge tests. The LSI
      identifies 4 learning styles, (Assimilating Diverging, Accommodating, and
      Converging). In some cases, learners present a balanced learning profile-an
      emphasis of all four equally. Statistical analysis consisted of t-tests and
      ANOVA. RESULTS: HF knowledge scores post-HPS compared to pre-HPS scores revealed
      a mean improvement of 7 points (p<0.001) showing evidence of learning. Within
      group score increases between the pre-test and post-test were seen for the
      Assimilating (66.68+/-20.87 to 83.35+/-12.59; p=0.07), Diverging (61.95+/-11.08
      to 69.86+/-12.33; p<0.01) and balanced profiles (64.4+/-12.45 to 71.8+/-10.14;
      p<0.01), but not for Converging or Accommodating profiles (73% of sample). Post
      hoc paired t-tests revealed a large effect size for the Assimilators (0.91) and
      moderate effect sizes for both the Divergers and balanced profiles (0.67 and
      0.65, respectively). CONCLUSION: These findings confirm that knowledge gains
      occur with HPS and provide evidence that HPS is an effective teaching methodology
      for nursing students identifying with most types of learning styles.

PMID- 24931653
TI  - Editorial.

PMID- 24931654
TI  - Attitudes of patients with schizophrenia to psychiatric research.
AB  - Objective. To examine how patients with schizophrenia spectrum disorders view
      psychiatric research and what influences their readiness to participate. Methods.
      A sample of 83 patients with schizophrenia spectrum disorders was examined using
      a specific self-report questionnaire designed for the purpose of the study.
      Results. Most patients (97%) approved at least "a little" of psychiatric research
      in general. There was a tendency to approve of psychosocial rather than
      biological research subjects (e.g., research on the role of traumatic life events
      was approved by 95% of patients as compared to 72% in the case of genetics and
      76% in the case of medication studies). Reasons to participate were mainly
      altruistic, only a minority found that monetary incentives were important.
      Another important reason was to improve individual chances of recovery. A large
      majority (95%) found it important to get sufficient information prior to the
      start but also to receive the results of the study. Conclusion. Patients'
      capability of critically appraising psychiatric research as well as their role in
      the research process should inform future research to ensure a more cooperative
      practice. 

PMID- 24931655
TI  - Clinical manifestations of mental disorders among Sesotho speakers.
AB  - Objective. The goal of this study was to compare four Sesotho-speaking clinical
      groups in South Africa concerning the manifestation of mental disorders. Methods.
      The participants were Sesotho speakers suffering from major depressive disorder,
      schizophrenia, anxiety disorders and substance abuse. The participants (N=407)
      were assessed and diagnosed by a multi-professional team. A clinical interview
      was then conducted with each participant and the symptomatology compared with the
      DSM-IV-TR criteria. Results. Differences among the four clinical groups were
      found regarding age, gender, marital status, substance abuse and aggressive
      behavior. Although the symptomatology of all four groups overlapped with that of
      their counterparts in Western cultures, some differences were noted. For example,
      delusions and hallucinations seem to be more prevalent in the Sesotho speakers
      with major depressive disorder and anxiety disorders than in Westernized groups.
      Traditional medicine remains the first treatment of choice for a significant
      number of the participants. It is recommended that traditional medicine should be
      incorporated into the national health system. Conclusion. In multicultural
      societies such as South Africa, further research regarding cultural differences
      in the clinical manifestation of mental disorders is urgently needed in order to
      make the necessary provision for cultural uniqueness. 

PMID- 24931656
TI  - Effects of amisulpride on the cognitive function of patients with schizophrenia
      who switched from risperidone.
AB  - Objectives. The aims of this 13-week study were to examine the efficacy and
      safety of amisulpride, and effects on cognitive function in patients with
      schizophrenia after they switched from risperidone. Methods. Twenty-three
      patients with schizophrenia whose antipsychotic was switched from risperidone to
      amisulpride were recruited. The efficacy, safety, and cognitive function were
      assessed. Results. Significant improvements were noted in the PANSS, CGI-S, and
      MADRS. The prolactin level, but not any of the remaining laboratory variables,
      increased significantly. The cognitive function improved significantly,
      particularly in memory subtests. Conclusions. Switching antipsychotic from
      risperidone to amisulpride in schizophrenia might have significantly improved not
      only the efficacy, but also various domains of cognitive function. However,
      hyperprolactinemia existed and was sometimes even worse. 

PMID- 24931657
TI  - Awareness of the metabolic syndrome in patients with bipolar disorder: A
      comparison of US and European psychiatrists.
AB  - Introduction. The metabolic syndrome is a relatively new concept still being
      debated in the US and Europe; little is known about how it is factored into
      psychiatric treatment decisions. Method. Practicing psychiatrists in the US
      (n=500) and five European countries (UK, France, Italy, Germany, Spain; n=718)
      participated in brief online surveys in 2005 and 2006. Results. US psychiatrists
      were more likely than EU psychiatrists surveyed to view metabolic syndrome as a
      significant health risk; US respondents reported significantly more bipolar
      patients who were overweight or obese, but similar percentages of bipolar
      patients who met criteria for the metabolic syndrome. More US than EU
      psychiatrists reported monitoring metabolic parameters before and during
      treatment, and generally were more concerned about bipolar medication adverse
      effects (AEs). Significantly more US psychiatrists indicated that they were
      extremely or very concerned about weight gain as an AE. Conclusions. For most
      surveyed US and EU psychiatrists, metabolic health is an important concern in the
      treatment of bipolar disorder. US psychiatrists reported more often monitoring
      metabolic parameters and adjusting treatment if abnormalities become evident, but
      practices are evolving in the US and EU. 

PMID- 24931658
TI  - Effect of risperidone on serum lipids and cerebrovascular mortality among elderly
      dementia patients with associated behavioral disturbances.
AB  - Background. Concern exists about safety of risperidone in glucose and lipid
      metabolism as well as cerebrovascular mortality. Our aim is to evaluate the
      safety of low-dose risperidone in elderly dementia patients with associated
      behavioral disturbances on glucose, serum lipids and cerebrovascular mortality.
      Material and methods. Thirty-one patients entered the study. Fasting glucose,
      total cholesterol, LDL, HDL, BMI, waist circumference, and triglycerides were
      measured at baseline and after 3 months. Mortality was reported after 6 months of
      starting the study. Risk factors for cerebrovascular disease were reported. A
      control group with 30 subjects was included. Results. Eighteen women and 13 men
      were included. Mean age was 80.6 years. After analyzing the different variables
      no significant differences between baseline and after 3 months of follow-up were
      found. During the study seven (22.58%) patients died, one from stroke. The most
      frequent associated cerebrovascular risk factors were smoking history, valvular
      heart disease and atrial fibrillation. Conclusion. In our study, low-dose
      risperidone administered in patients with behavioral symptoms associated dementia
      does not affect significantly the lipid profile, fasting glucose, BMI or waist
      circumference and is not associated with an increased risk for cerebrovascular
      mortality. 

PMID- 24931659
TI  - Olanzapine in the treatment of depression with psychotic features: A prospective
      open-label study.
AB  - Objective. Depression with psychotic features is a severe subtype of major
      depression associated with the presence of delusions, hallucinations and specific
      neurobiological features. Despite clinical consensus and guideline
      recommendations, data comparing the efficacy of combining antipsychotics with
      antidepressants compared to antidepressants alone remain inconclusive. The aim of
      the study was to investigate effectiveness and tolerability of the atypical
      antipsychotic olanzapine in acute depression with psychotic features. Methods.
      Seventeen inpatients with major depressive disorder with psychosis (MDDp) were
      treated with a combination of an antidepressant and olanzapine for 6 weeks in a
      prospective open-label study. Depressive and psychotic symptoms, extrapyramidal
      and general side effects were assessed every 2 weeks. Sixteen patients were
      eligible for final analysis. Results. The Brief Psychiatric Rating Scale (BPRS)
      showed a 30% symptom reduction after week 2, a 45% symptom reduction after week 4
      and no considerable improvement thereafter. Depressive symptoms (Bech-Rafaelsen
      Melancholia Scale, BRMS) receded by 37% after week 2 and 50% after week 4. No
      extrapyramidal side effects occurred. Conclusion. Olanzapine is effective and
      tolerable in combination with an antidepressant in an MDDp inpatient sample. The
      results concur with data supporting good efficacy in negative and depressive
      symptoms of patients with schizophrenic and schizoaffective diseases. 

PMID- 24931660
TI  - The use of academic detailing to improve evidence based prescribing of
      risperidone long acting injection.
AB  - Objective. It takes 6 weeks for plasma levels of risperidone long-acting
      injection (RLAI) to reach steady state, and randomised controlled trials
      demonstrate a flat dose-response curve. In clinical practice, the dose of RLAI is
      often increased rapidly at the start of treatment and many patients receive a
      dose above 25 mg/2 weeks. We sought to understand why and to use academic
      detailing as a catalyst for change. Method. (1) Semi-structured interview of and
      academic detailing visit to psychiatrists. (2) Number of pharmacy issues or each
      strength of RLAI issues before and after the academic detailing visit. Results.
      Understanding of the pharmacokinetics of RLAI and the flat dose-response curve
      were poor. After a single visit from an academic detailer, the proportion of 50
      mg doses issued decreased from 44 to 31%. Conclusion. Academic detailing was
      effective in changing prescribing practice; patients are likely to benefit
      through receiving treatment that has a better risk-benefit ratio, and the
      healthcare organization is likely to benefit, in terms of more cost-effective
      prescribing. 

PMID- 24931661
TI  - Long-term, naturalistic treatment with olanzapine, risperidone, quetiapine, or
      haloperidol monotherapy: 24-month results from the Intercontinental Schizophrenia
      Outpatient Health Outcomes (IC-SOHO) study.
AB  - Objective. To compare the effectiveness of olanzapine, risperidone, quetiapine,
      or haloperidol monotherapy in patients with schizophrenia who were treated in
      routine clinical practice settings for a period of 2 years. The incidence and
      persistence of adverse events encountered during long-term therapy are also
      reported. Method. Outpatients with schizophrenia who entered this 3-year,
      prospective, observational study were classified according to their initially
      prescribed antipsychotic monotherapy: olanzapine (n=3222), risperidone (n=1116),
      quetiapine (n=189), or haloperidol (n=256). Patients were included in the
      analysis for as long as this treatment was maintained. Results. Over 2 years,
      olanzapine recipients had significantly (P<=0.001) greater reduction in overall
      CGI-S score (and the negative, depressive, and cognitive symptoms domains), lower
      incidence of sexual and motor dysfunction, and greater odds of response compared
      to risperidone or haloperidol-treated patients. However, olanzapine patients
      gained more weight than patients in other treatment groups. The incidence of
      motor dysfunction was significantly (P<=0.001) greater in haloperidol-treated
      patients, relative to the atypical treatment groups. Conclusion. The results of
      this observational study indicate that, in these patients with schizophrenia,
      long-term monotherapy with olanzapine may offer benefits over risperidone and
      haloperidol, but the potential for weight gain should be considered in the
      clinical management of these patients. 

PMID- 24931662
TI  - The clinical use of plasma clozapine levels in a maximum security setting.
AB  - Background. Research suggests a correlation between clozapine dose, plasma level
      and therapeutic response. Plasma clozapine levels may, therefore, be useful in
      practice. Little evidence exists, however, on the indications for, and outcome
      of, levels being undertaken or their use in maximum security settings. Objective.
      To determine if plasma clozapine levels are useful in clinical practice by
      analysing their use at the maximum-security State Hospital, Carstairs. Methods.
      All plasma clozapine levels (until March 2004) undertaken at the State Hospital,
      clinical indication and outcome were analysed by retrospective case note
      analysis. These results were compared with the published literature. Results. A
      total of 140 plasma clozapine levels were analysed. The average level was 0.61
      mg/l and dose was 622.9 mg/day. The indications for and consequences of levels
      are demonstrated. A positive correlation of 0.217 was calculated. Conclusion.
      This paper shows that plasma clozapine levels are most useful in managing side
      effects and suspected non-compliance. Plasma clozapine levels are, therefore,
      useful in clinical practice. 

PMID- 24931663
TI  - Improving ECT practice with a care pathway: hits and misses.
AB  - Objective. To evaluate the effectiveness of a care pathway for the use of
      electroconvulsive therapy (ECT) in a UK psychiatric inpatient unit. Methods. A
      completed clinical audit cycle of the care pathway and variance from it. Results.
      Sixty courses of treatment were reviewed. All were given for severe depressive
      disorder. Consent was recorded for all but one course. Clinical assessments were
      completed for 96% during and 50% after treatment. Conclusions. Use of a care
      pathway enhanced aspects of the clinical practice of ECT, although the overall
      effect was inconsistent. ECT was not used to treat schizophrenia. Maintenance ECT
      continues to be used despite the recent NICE guidance on this subject. The care
      pathway ensured regular clinical assessment of patients during their courses of
      ECT. 

PMID- 24931664
TI  - Effectiveness of a structured diet program in antipsychotic-induced weight gain
      in patients with schizophrenia.
AB  - Objective.The aim of this study was to evaluate the effectiveness of a structured
      diet program in weight loss in patients with schizophrenia. Methods. A total of
      38 outpatients diagnosed with schizophrenia according to DSM-IV and who had
      complaints of weight gain during treatment with various antipsychotic drugs were
      invited to participate in a 3-month structured diet program. Thirty-two patients
      and another 40 patients were included as the control group. At the beginning of
      the diet program, the patients were given a form in order to evaluate their
      eating habits, and blood samples were taken to measure plasma lipid profile, and
      fasting blood glucose (FBG) level. Patients' baseline weight, body mass index
      (BMI), and basal metabolism rate (BMR) were recorded. Results. Thirty-two
      patients with schizophrenia, who attended a 3-month structured diet program had
      mean weight loss of 6.19 kg, whereas patients in the control group gained 1.6 kg.
      Conclusion. Our findings show that a diet program is effective in managing
      antipsychotic-induced weight gain. The degree of weight loss seems to be
      correlated with the duration in which the patient is on the diet program.
      However; younger patients had less benefit from the diet program. 

PMID- 24931665
TI  - Concepts and controversies of juvenile myoclonic epilepsy: still an enigmatic
      epilepsy.
AB  - Juvenile myoclonic epilepsy (JME) is a clinically and genetically heterogenous,
      generalized epilepsy syndrome usually starting in adolescence. An age-related,
      predominantly frontocortical-subcortical network dysfunction is likely to be the
      substrate of bilateral myoclonic seizures occurring at full consciousness within
      hours after awakening, which are the clinical hallmark of JME. Although essential
      features of JME were recognized by Herpin more than 140 years ago, it is still an
      enigmatic epilepsy syndrome in many ways; advanced imaging techniques reveal
      multi-focal abnormalities in this paradigmatic generalized epilepsy syndrome;
      clinical studies reveal a major role of genetics in etiology, but the underlying
      molecular changes are likely to be highly heterogeneous; many JME patients have
      psycho-social issues, even though their intelligence is normal; antiepileptic
      drugs (AEDs), notably valproic acid, achieve seizure remission in two thirds of
      patients, but more patients seem to relapse after stopping AEDs than in any other
      epilepsy syndrome. This pessimistic outlook has been challenged in recent
      population-based studies and needs to be assessed in randomized AED withdrawal
      trials. This review summarizes recent focus neuroimaging, genetic, and behavioral
      aspects of JME and re-appraises the entrenched view that remission off AEDs is
      exceptionally rare in JME. 

PMID- 24931666
TI  - Enzymatically induced motion at nano- and micro-scales.
AB  - In contrast to adenosine triphosphate (ATP)-dependent motor enzymes, other
      enzymes are little-known as "motors" or "pumps", that is, for their ability to
      induce motion. The enhanced diffusive movement of enzyme molecules, the self
      propulsion of enzyme-based nanomotors, and liquid pumping with enzymatic
      micropumps were indeed only recently reported. Enzymatically induced motion can
      be achieved in mild conditions and without the use of external fields. It is thus
      better suited for use in living systems (from single-cell to whole-body) than
      most other ways to achieve motion at small scales. Enzymatically induced motion
      is thus not only new but also important. Therefore, the present work reviews the
      most significant discoveries in enzymatically induced motion. As we will learn,
      freely diffusing enzymes enhance their diffusive movement by nonreciprocal
      conformational changes which parallel their catalytic cycles. Meanwhile, enzyme
      modified nano- and micro-objects turn chemical energy into kinetic energy through
      mechanisms such as bubble recoil propulsion, self-electrophoresis, and self
      diffusiophoresis. Enzymatically induced motion of small objects ranges from
      enhanced diffusive movement to directed motion at speeds as high as 1 cm s(-1).
      In spite of the progress made in understanding how the energy of enzyme reactions
      is turned into motion, most enzymatically powered devices remain inefficient and
      need improvements before we will witness their application in real world
      environments. 

PMID- 24931668
TI  - p38alpha mitogen-activated kinase mediates cardiomyocyte apoptosis induced by
      palmitate.
AB  - RATIONALE: The mechanisms underlying lipotoxic/diabetic cardiomyopathy remain
      poorly understood. Saturated fatty acid (SFA) levels, elevated in obesity and
      type 2 diabetes, induce apoptosis in many cell types including cardiomyocytes.
      Signaling pathways, including the p38alpha mitogen-activated kinase (MAPK)
      dependent pathway, have been implicated in apoptosis due to a diverse range of
      insults. OBJECTIVE: We tested the hypothesis that SFA-induced cardiomyocyte
      apoptosis is dependent on p38alpha activation. METHODS AND RESULTS: Human adult
      ventricular cardiomyocytes (AC16 cells) were exposed to high physiological levels
      of palmitate (PA), a SFA. The apoptotic response was measured using annexin-V by
      flow cytometry, and the p38alpha-dependent pathway was evaluated using a p38
      inhibitor PD169316, and by p38alpha small interfering RNA (siRNA) knockdown. PA
      exposure for 16 h dose-dependently increased apoptosis in AC16 cardiomyocytes
      (control: 2.6+/-0.6%, 150 MUM PA: 3.5+/-0.9%, 300 MUM PA: 11.5+/-1.6%, n=4,
      p<0.01). PA did not change total p38alpha protein levels, but increased p38alpha
      phosphorylation dose-dependently (n=5, p<0.01). PD169316 tended to reduce PA
      induced apoptosis (n=4, p=0.05). Specific p38alpha siRNA markedly reduced the
      expression of p38alpha but not p38beta (n=3, p<0.0001), and dose-dependently
      attenuated PA-induced apoptosis (control siRNA: 7.7+/-1.0%, 300 MUM PA: 34.4+/
      5.0%, 300 MUM PA+30 pmol siRNA: 23.7+/-4.4%, 300 MUM PA+60 pmol siRNA: 19.7+/
      2.6%, 300 MUM PA+120 pmol siRNA: 17.3+/-2.8%, n=4, p<0.0001). CONCLUSIONS: These
      results demonstrate that PA induces p38alpha activation, and reducing p38alpha
      expression attenuates PA-induced cardiomyocyte apoptosis. Our results support a
      potential mechanism by which high plasma SFA levels through p38alpha activation
      may lead to the development of lipotoxic/diabetic cardiomyopathy.

PMID- 24931667
TI  - CEACAM1 promotes melanoma cell growth through Sox-2.
AB  - The prognostic value of the carcinoembryonic antigen cell adhesion molecule 1
      (CEACAM1) in melanoma was demonstrated more than a decade ago as superior to
      Breslow score. We have previously shown that intercellular homophilic CEACAM1
      interactions protect melanoma cells from lymphocyte-mediated elimination. Here,
      we study the direct effects of CEACAM1 on melanoma cell biology. By employing
      tissue microarrays and low-passage primary cultures of metastatic melanoma, we
      show that CEACAM1 expression gradually increases from nevi to metastatic
      specimens, with a strong dominance of the CEACAM1-Long tail splice variant. Using
      experimental systems of CEACAM1 knockdown and overexpression of selective
      variants or truncation mutants, we prove that only the full-length long tail
      variant enhances melanoma cell proliferation in vitro and in vivo. This effect is
      not reversed with a CEACAM1-blocking antibody, suggesting that it is not mediated
      by intercellular homophilic interactions. Downstream, CEACAM1-Long increases the
      expression of Sox-2, which we show to be responsible for the CEACAM1-mediated
      enhanced proliferation. Furthermore, analysis of the CEACAM1 promoter reveals two
      single-nucleotide polymorphisms (SNPs) that significantly enhance the promoter's
      activity compared with the consensus nucleotides. Importantly, case-control
      genetic SNP analysis of 134 patients with melanoma and matched healthy donors
      show that patients with melanoma do not exhibit the Hardy-Weinberg balance and
      that homozygous SNP genotype enhances the hazard ratio to develop melanoma by
      35%. These observations shed new mechanistic light on the role of CEACAM1 in
      melanoma, forming the basis for development of novel therapeutic and diagnostic
      technologies. 

PMID- 24931669
TI  - Ribozyme-independent replication of a defective hepatitis D virus RNA derived
      from hepatitis B/D patients receiving antiviral therapy.
AB  - Novel hepatitis D virus (HDV) RNA mutants carrying large fragment deletions were
      identified in the serum samples of two hepatitis B/D patients receiving antiviral
      therapy. Sequence analysis revealed that the deleted regions encompassed both
      ribozyme domains. The mutant persisted in the serum samples for at least 2 and 10
      months, respectively in the two patients, raising the question of whether such
      mutants could replicate in the absence of ribozyme domains. Thirty anti-HDV
      antibody-positive serum samples derived from 17 patients receiving antiviral
      therapy were submitted for RT-PCR detection of HDV RNA deletion mutants. Large
      fragment HDV RNA deletions were found in 4 patients. Of them, two had liver
      biopsy samples available. Northern blot analysis revealed high molecular weight
      HDV RNA replication intermediates, genomic and anti-genomic senses, in the liver
      tissues. Transfection of an in vitro transcribed HDV RNA deletion mutant (1.28
      kb) into Huh7 and HepG2 cells also resulted in generation of high molecular
      weight HDV RNA species in the hepatoma cells (>6.5 kb) with secretion of a 6.5 kb
      HDV RNA species into the medium. In conclusion, we discovered novel large
      fragment deletion mutants of HDV RNA in hepatitis B/D patients receiving
      antiviral therapy. Such mutants did not contain ribozyme domains but could
      replicate in the liver cells to generate high molecular weight but not unit
      length HDV RNA.

PMID- 24931671
TI  - Two novel mutations in COII and tRNA(His) mitochondrial genes in
      asthenozoospermic infertiles men.
AB  - In this study we performed a systematic sequence analysis of 7 mitochondrial
      genes (cytochrome oxidase I, cytochrome oxidase II, cytochrome oxidase III,
      adenosine triphosphate synthase6, ATP synthase8, cytochrome b and tRNA(His)) in
      64 infertile men suffering from asthenospermia (n=31) in comparison to
      normospermic infertile men (n=33) from Tunisian population. A total of 92
      nucleotide substitutions in sperm mitochondrial DNA were found; 88 of them were
      previously identified and reported in the human mitochondrial DNA database
      (www.mitomap.org) and 4 were novel. We also detected in 4 asthenospermic patients
      a double novels mutations, the first was found in COXII gene (m.8021 G/A) that
      was absent in normospermic infertile men. This mutation substituting the
      Isoleucine at position 146 to Valine in a conserved amino acid in the
      transmembrane functional domain of the protein. And the second was detected in
      the tRNA(His) gene (m.12187C>A) this mutation was found in homoplasmic state and
      was absent in normospermic patients. It was conserved throughout evolution and
      affects a wobble adenine in the T-loop region at the 54 codon of mitochondrial
      tRNA(His) . 

PMID- 24931672
TI  - 14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against
      oxygen/glucose deprivation-induced apoptosis.
AB  - 14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is
      enriched in the brain cortex and exerts protective effect against neuronal
      apoptosis induced by ischemia/reperfusion. Although apoptosis has been well
      recognized to be closely associated with mitochondrial biogenesis and function,
      it is still unclear whether the neuroprotective effect of 14,15-EET is mediated
      by promotion of mitochondrial biogenesis and function in cortical neurons under
      the condition of oxygen-glucose deprivation (OGD). In this study, we found that
      14,15-EET improved cell viability and inhibited apoptosis of cortical neurons.
      14,15-EET significantly increased the mitochondrial mass and the ratio of
      mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis,
      peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC
      1alpha), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription
      factor A (TFAM), were elevated at both mRNA and protein levels in the cortical
      neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the
      decline of mitochondrial membrane potential, reduced ROS, while increased ATP
      synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA
      blunted the up-regulation of PGC-1alpha and NRF-1 stimulated by 14,15-EET, and
      consequently abolished the neuroprotective effect of 14,15-EET. Our results
      indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting
      mitochondrial biogenesis and function through CREB mediated activation of PGC
      1alpha and NRF-1. 

PMID- 24931670
TI  - Mannose metabolism: more than meets the eye.
AB  - Mannose is a simple sugar with a complex life. It is a welcome therapy for
      genetic and acquired human diseases, but it kills honeybees and blinds baby mice.
      It could cause diabetic complications. Mannose chemistry, metabolism, and
      metabolomics in cells, tissues and mammals can help explain these multiple
      systemic effects. Mannose has good, bad or ugly outcomes depending on its steady
      state levels and metabolic flux. This review describes the role of mannose at
      cellular level and its impact on organisms. 

PMID- 24931673
TI  - Determination of personalized diabetes treatment plans using a two-delay model.
AB  - Diabetes cases worldwide have risen steadily over the past few decades, lending
      urgency to the search for more efficient, effective, and personalized ways to
      treat the disease. Current treatment strategies, however, may fail to maintain
      oscillations in blood glucose concentration that naturally occur multiple times
      per day, an important element of normal human physiology. Building upon recent
      successes in mathematical modeling of the human glucose-insulin system, we show
      that both food intake and insulin therapy likely demand increasingly precise
      control over insulin sensitivity if oscillations at a healthy average glucose
      concentration are to be maintained. We then model and describe personalized
      treatment options for patients with diabetes that maintain these oscillations. We
      predict that for a person with type II diabetes, both blood glucose levels can be
      controlled and healthy oscillations maintained when the patient gets an hour of
      daily exercise and is placed on a combination of Metformin and sulfonylurea
      drugs. We note that insulin therapy and an additional hour of exercise will
      reduce the patient's need for sulfonylureas. Results of a modeling analysis
      suggest that, with constant nutrition and controlled exercise, the blood glucose
      levels of a person with type I diabetes can be properly controlled with insulin
      infusion between 0.45 and 0.7MUU/mlmin. Lastly, we note that all suggested
      strategies rely on existing clinical techniques and established treatment
      measures, and so could potentially be of immediate use in the design of an
      artificial pancreas. 

PMID- 24931674
TI  - A survey on computational approaches to identifying disease biomarkers based on
      molecular networks.
AB  - The disease biomarkers can help make accurate diagnosis and therefore give
      appropriate interventions. In the past years, the accumulation of various kinds
      of 'omics' data, e.g. genomics and transcriptomics, makes it possible to identify
      disease biomarkers in a more efficient way. In particular, the molecular networks
      that describe the functional relationships among molecules enable the
      identification of disease biomarkers from a systematic perspective. In this
      paper, we surveyed the recent progress on the computational approaches that have
      been developed to identify disease biomarkers based on molecular networks. In
      addition, we introduced the popular resources about human interactomes and
      regulatomes as well as human diseasomes, whose availability makes it possible to
      predict the disease biomarkers with the utility of networks. 

PMID- 24931676
TI  - EdgeMarker: Identifying differentially correlated molecule pairs as edge
      biomarkers.
AB  - Biomarker discovery is one of the major topics in translational biomedicine study
      based on high-throughput biological data analysis. Traditional methods focus on
      differentially expressed genes (or node-biomarkers) but ignore non-differentials.
      However, non-differentially expressed genes also play important roles in the
      biological processes and the rewired interactions / edges among non-differential
      genes may reveal fundamental difference between variable conditions. Therefore,
      it is necessary to identify relevant interactions or gene pairs to elucidate the
      molecular mechanism of complex biological phenomena, e.g. distinguish different
      phenotypes. To address this issue, we proposed a new method based on a new vector
      representation of an edge, EdgeMarker, to (1) identify edge-biomarkers, i.e. the
      differentially correlated molecular pairs (e.g., gene pairs) with optimal
      classification ability, and (2) transform the 'node expression' data in node
      space into the 'edge expression' data in edge space and classify the phenotype of
      each single sample in edge space, which generally cannot be achieved in
      traditional methods. Unlike the traditional methods which analyze the node space
      (i.e. molecular expression space) or higher dimensional space using arbitrary
      kernel methods, this study provides a mathematical model to explore the edge
      space (i.e. correlation space) for classification of a single sample. In this
      work, we show that the identified edge-biomarkers indeed have strong ability in
      distinguishing normal and disease samples even when all involved genes are not
      significantly differentially expressed. The analysis of human cholangiocarcinoma
      dataset and diabetes dataset also suggested that the identified edge-biomarkers
      may cast new biological insights into the pathogenesis of human complex diseases.

PMID- 24931675
TI  - Derivation and experimental comparison of cell-division probability densities.
AB  - Experiments have shown that, even in a homogeneous population of cells, the
      distribution of division times is highly variable. In addition, a homogeneous
      population of cells will exhibit a heterogeneous response to drug therapy. We
      present a simple stochastic model of the cell cycle as a multistep stochastic
      process. The model, which is based on our conception of the cell cycle
      checkpoint, is used to derive an analytical expression for the distribution of
      cell cycle times. We demonstrate that this distribution provides an accurate
      representation of cell cycle time variability and show how the model relates drug
      induced changes in basic biological parameters to variability in response to drug
      treatment. 

PMID- 24931677
TI  - Evolution of the first genetic cells and the universal genetic code: a hypothesis
      based on macromolecular coevolution of RNA and proteins.
AB  - A qualitative hypothesis based on coevolution of protein and nucleic acid
      macromolecules was developed to explain the evolution of the first genetic cells,
      from the likely organic chemical-rich environment of early earth, through to the
      Last Universal Common Ancestor (LUCA). The evolution of the first genetic cell
      was divided into three phases, proto-genetic cells I, II and III, and the
      transition to each milestone is described, based on development of chemical cross
      catalysis, bio-cross-catalysis, and the universal genetic code, respectively.
      Selection of macromolecular properties of both peptides and nucleic acids, in
      response to environmental factors, was likely to be a key aspect of early
      evolution. The development of hereditable nucleic acids with various key
      functions; translation, transcription and replication, is described. These
      functions are envisaged to have coevolved with protein enzymes, from simple
      organic precursors. Genetically heritable nucleotides may have developed after
      the local earth environment had cooled below 63  degrees C. Around this
      temperature G-C bases would have been preferentially utilized for nucleotide
      synthesis. Under these conditions RNA type nucleotides were then likely selected
      from a range of different types of nucleotide backbones through template-based
      synthesis. Initial development of the genetic coding system was simplified by the
      availability of proto-messenger RNA sequences that contained only G and C bases,
      and the need to encode only four amino acids. The step-wise addition of further
      amino acids to the code was predicted to parallel the growing metabolic
      complexity of the proto-genetic cell. On completion of this evolutionary process
      the proto-genetic cell is envisaged to have become the LUCA, the last common
      ancestor of bacteria, eukaryote and archaea domains. Key issues addressed by the
      model include: (a) the transition from non-hereditable random sequences of
      peptides and nucleic acids to specific proteins coded by hereditable nucleotide
      sequences, (b) the origin of homochiral amino acids and sugars, and (c) the
      mutation limits on the sizes of early nucleic acid genomes. The first genome was
      limited to a size of about 200 base pairs.

PMID- 24931678
TI  - Thank you Pernille!

PMID- 24931680
TI  - The World (fizzy drink) Cup 2014.

PMID- 24931681
TI  - The UK Medical Innovation Bill: hype and hope.

PMID- 24931683
TI  - Can Coca Cola promote physical activity?

PMID- 24931684
TI  - Top 15 UK research priorities for preterm birth.

PMID- 24931685
TI  - Metabolic mediators of body-mass index and cardiovascular risk.

PMID- 24931686
TI  - Metabolic mediators of body-mass index and cardiovascular risk.

PMID- 24931687
TI  - Metabolic mediators of body-mass index and cardiovascular risk--authors' reply.

PMID- 24931688
TI  - Delirium in elderly people.

PMID- 24931689
TI  - Tobacco in China.

PMID- 24931690
TI  - Delirium in elderly people--authors'reply.

PMID- 24931691
TI  - Dentists should be at the forefront in the fight against sugar.

PMID- 24931692
TI  - Severe hypercalcaemia, nephrocalcinosis, and multiple paraffinomas caused by
      paraffin oil injections in a young bodybuilder.

PMID- 24931693
TI  - Accuracy of cytology in distinguishing adrenocortical tumors from
      pheochromocytoma in companion animals.
AB  - BACKGROUND: The distinction between adrenocortical tumors and pheochromocytoma
      can be challenging using clinical findings, diagnostic imaging and laboratory
      tests. Cytology might be a simple, minimally invasive method to reach a correct
      diagnosis. OBJECTIVES: The purpose of this study was to assess the accuracy of
      cytology in differentiating cortical from medullary tumors of the adrenal glands
      in dogs and cats. METHODS: Cytologic key features of adrenocortical tumors and
      pheochromocytoma were defined by one reference author. Cytologic specimens from
      primary adrenal tumors were submitted to 4 cytopathologists who were asked to
      classify the tumors based on the previously defined key features without
      knowledge of previous classification. RESULTS: Twenty specimens from
      histologically confirmed adrenal tumors (Group 1) and 4 specimens from adrenal
      tumors causing adrenal-dependent Cushing's syndrome (Group 2) were evaluated by
      the 4 cytopathologists. Accuracy in differentiating cortical from medullary
      origin ranged from 90% to 100%, with a Kappa coefficient of agreement between
      cytopathologists of 0.95. CONCLUSIONS: The origin of an adrenal tumor can be
      easily determined by cytology alone in many cases. However, cytology was not
      reliable in distinguishing benign from malignant neoplasia. Additional studies
      are needed to assess possible risks and complications associated with fine-needle
      biopsy of adrenal tumors in dogs and cats.

PMID- 24931694
TI  - Activation of the carbohydrate response element binding protein (ChREBP) in
      response to anoxia in the turtle Trachemys scripta elegans.
AB  - BACKGROUND: ChREBP (carbohydrate response element binding protein) is a glucose
      responsive transcription factor that is known to be an important regulator of
      glycolytic and lipogenic genes in response to glucose. We hypothesized that
      activation of ChREBP could be relevant to anoxia survival by the anoxia-tolerant
      turtle, Trachemys scripta elegans. METHODS: Expression of ChREBP in response to 5
      and 20h of anoxia was examined using RT-PCR and Western immunoblotting. In
      addition, subcellular localization and DNA-binding activity of ChREBP protein
      were assessed and transcript levels of liver pyruvate kinase (LPK), a downstream
      gene under ChREBP control were quantified using RT-PCR. RESULTS: ChREBP was
      anoxia-responsive in kidney and liver, with transcript levels increasing by 1.2
      1.8 fold in response to anoxia and protein levels increasing by 1.8-1.9 fold.
      Enhanced nuclear presence under anoxia was also observed in both tissues by 2.2
      2.8 fold. A 4.2 fold increase in DNA binding activity of ChREBP was also observed
      in liver in response to 5h of anoxia. In addition, transcript levels of LPK
      increased by 2.1 fold in response to 5h of anoxia in the liver. CONCLUSIONS: The
      results suggest that activation of ChREBP in response to anoxia might be a
      crucial factor for anoxia survival in turtle liver by contributing to elevated
      glycolytic flux in the initial phases of oxygen limitation. GENERAL SIGNIFICANCE:
      This study provides the first demonstration of activation of ChREBP in response
      to anoxia in a natural model of anoxia tolerance, further improving our
      understanding of the molecular nature of anoxia tolerance.

PMID- 24931695
TI  - Stabilization of VEGF G-quadruplex and inhibition of angiogenesis by quindoline
      derivatives.
AB  - BACKGROUND: Angiogenesis is thought to be important in tumorigenesis and tumor
      progress. Vascular endothelial growth factor (VEGF) is a pluripotent cytokine and
      angiogenic growth factor that plays crucial roles in embryonic development and
      tumor progression. In many types of cancer, VEGF is overexpressed and is
      generally associated with tumor progression and survival rate. The
      polypurine/polypyrimidine sequence located upstream of the promoter region in the
      human VEGF gene can form specific parallel G-quadruplex structures, raising the
      possibility for transcriptional control of VEGF through G-quadruplex ligands.
      METHODS: PCR stop assay, circular dichroism (CD) spectra, RNA extraction and RT
      PCR, enzyme-linked immunosorbent assay (ELISA), luciferase Assays, cell scrape
      test, xCELLigence real-time cell analysis (RTCA), and chick embryo
      chorioallantoic membrane (CAM) assay. RESULTS AND CONCLUSIONS: We found that
      quindoline derivatives can interact with the G-rich DNA sequences of the VEGF
      promoter to stabilize this G-quadruplex and suppress the transcription and
      expression of the VEGF protein. We also demonstrated that these derivatives
      exhibit potential anti-angiogenic activity in chick embryos and antitumor
      activity, including the inhibition of cell proliferation and migration. GENERAL
      SIGNIFICANCE: Our new findings have significances not only for understanding the
      mechanism of the G-quadruplex ligands mediating the VEGF transcription
      inhibition, but also for exploring a new anti-tumor strategy to blocking the
      transcription of VEGF to inhibit the angiogenesis in cancer cells.

PMID- 24931696
TI  - Reflux composition influences the level of NF-kappaB activation and upstream
      kinase preference in oesophageal adenocarcinoma cells.
AB  - Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor.
      Understanding the molecular basis of this malignancy is key to finding new
      prevention and treatment strategies. Gastroesophageal reflux disease is the
      primary cause of OA, usually managed with acid suppression therapy. However, this
      often does little to control carcinogenic bile acid reflux. The transcription
      factor nuclear factor kappa B (NF-kappaB) plays a key role in the pathogenesis of
      OA and its activity is associated with a poor response to chemotherapy, making it
      an attractive therapeutic target. We sought to decipher the role of different
      bile acids in NF-kappaB activation in oesophageal cell lines using short,
      physiologically relevant exposure times. The effect of an acidic or neutral
      extracellular pH was investigated concurrently, to mimic in vivo conditions
      associated with or without acid suppression. We found that some bile acids
      activated NF-kappaB to a greater extent when combined with acid, whereas others
      did so in its absence, at neutral pH. The precise composition of an individual's
      reflux, coupled with whether they are taking acid suppressants may therefore
      dictate the extent of NF-kappaB activation in the oesophagus, and hence the
      likelihood of histological progression and chemotherapy success. Regardless of
      pH, the kinase inhibitor of kappaB kinase was pivotal in mediating reflux induced
      NF-kappaB activation. Its importance was confirmed further as its increased
      activation was associated with histological progression in patient samples. We
      identified further kinases important in acid or bile induced NF-kappaB signalling
      in oesophageal cells, which may provide suitable targets for therapeutic
      intervention. 

PMID- 24931697
TI  - Efficacy and safety of vertebral stenting for painful vertebral compression
      fractures in patients with metastatic disease.
AB  - BACKGROUND AND PURPOSE: Painful vertebral compression fractures in cancer
      patients reduce quality of life and may limit survival. We assessed pain relief,
      vertebral height restoration, and kyphosis correction following vertebral
      augmentation using a novel expandable titanium stent implant in cancer patients
      with painful vertebral compression fractures. MATERIALS AND METHODS: Patients >18
      years of age with metastatic disease who presented symptomatic compression
      fractures of vertebral bodies T5-L5, with or without a history of osteoporosis,
      were included in the study. Back pain at presentation, immediately after
      vertebral stenting, and at 1-, 3-, 6-, and 12-month follow-up was estimated using
      the visual analog scale (VAS). Vertebral height and local kyphotic angle (alpha
      angle) were measured on lateral standing X-ray before and 1-3 months after
      stenting. RESULTS: Forty-one cancer patients with painful vertebral compression
      fractures underwent vertebral stenting procedures at 55 levels. There was no
      perioperative mortality and no significant complication. Median preoperative VAS
      was 8.0 (range 8-10), falling to 2.0 immediately postop (range 1-6, P  =  0.000)
      and 0 at all subsequent follow-up (P <= 0.012). Mean preoperative vertical height
      loss was 25.8% (range 0-84.0%) versus a postoperative mean of 18.0% (range 0
      66.0%, P  =  0.000). Median pre- and postoperative kyphotic angle improved from
      8.3 degrees  (range 0.2 degrees -54.0 degrees ) to 7.1 degrees  (range 0.2
      degrees -25.0 degrees , P  =  0.000). Wilcoxon signed rank test or student's t
      test was used for comparisons. CONCLUSIONS: Vertebral augmentation using a novel
      vertebral stenting system provided immediate and enduring pain relief and
      improved vertebral height loss and kyphotic angle.

PMID- 24931698
TI  - Exceptional symmetric anterior brainstem involvement in leptomeningeal
      carcinomatosis.

PMID- 24931699
TI  - Mild traumatic brain injury in children: management practices in the acute care
      setting.
AB  - OBJECTIVE: Accurate diagnosis, treatment and follow up of children suffering mild
      traumatic brain injury (MTBI) is important as post-concussive symptoms and long
      term disability might occur. This research explored the decisions clinicians make
      in their assessment and management of children with MTBI in acute care settings,
      and identified barriers and enablers to the delivery of best-practice care.
      METHODS: A purposeful sample of 29 clinicians employed in two metropolitan
      paediatric EDs and one Urgent Care clinic was surveyed using a vignette-based
      questionnaire that also included domains of guideline awareness, attitudes to
      MTBI care, use of clinical decision support systems, and knowledge and skills for
      practising evidence-based healthcare. RESULTS: Overall, the evaluation and
      management of children presenting acutely with MTBI generally followed best
      practice guidelines, particularly in relation to identifying intracranial
      injuries that might require surgical intervention, observation for potential
      deterioration, adequate pain management and the provision of written head injury
      advice on discharge. Larger variation emerged in regard to follow-up care and
      referral pathways. Potential barriers to best- practice were lack of guideline
      awareness, attitudes to MTBI, and lack of time or other priorities. CONCLUSIONS:
      Opportunities exist to improve care for children who present in acute care
      settings following mild traumatic brain injury. These include having up-to-date
      guidelines that are consistent across acute care settings; providing clearer
      pathways for referral and follow up; targeting continuing medical education
      towards potential complications; and providing computerised decision support so
      that assessment and management are conducted systematically.

PMID- 24931700
TI  - A series of blue supramolecular polymers with different counterions for polymer
      light-emitting diodes.
AB  - A series of blue supramolecular polymers with different counterions based on host
      guest interactions were developed for polymer light-emitting diodes. It was found
      that the counterions play important roles in the resulting materials'
      supramolecular interactions as well as the device performance. 

PMID- 24931701
TI  - Prevalence and predictors of postpartum glucose intolerance in Italian women with
      gestational diabetes mellitus.
AB  - AIMS: To determine the prevalence of both prediabetes and type 2 diabetes
      mellitus (T2DM) by postpartum oral glucose tolerance test (ppOGTT) in Italian
      women diagnosed with gestational diabetes mellitus (GDM), and identify antepartum
      predictors of glucose intolerance. METHODS: Retrospective study of 454 Caucasian
      women that underwent a 75g OGTT between 6 and 12 weeks postpartum in Calabria
      (Southern Italy) between 2004 and 2012. Prediabetes and T2DM were diagnosed
      according to the American Diabetes Association (ADA) criteria. Data were examined
      by univariate analysis and multiple regression analysis. RESULTS: 290 women
      (63.9%) were normal, 146 (32.1%) had prediabetes (85 impaired fasting glycemia;
      61 impaired glucose tolerance), and 18 (4.0%) had T2DM. Of the continuous
      variables, pre-pregnancy body mass index (BMI), age at pregnancy, fasting plasma
      glucose (FPG) at gravid OGTT, and week at diagnosis of GDM were associated with
      prediabetes and T2DM, whereas the parity was associated with T2DM only. For
      categorical traits, pre-pregnancy BMI >= 25 and previous diagnosis of polycystic
      ovary syndrome (PCOS) emerged as the strongest predictors of prediabetes whereas
      the strongest predictors of T2DM were FPG >= 100 mg/dl (5.6 mmol/l) at GDM
      diagnosis and pre-pregnancy BMI >= 25. Moreover, FPG at GDM screening was a good
      predictor of T2DM after receiver-operating-characteristic analysis. CONCLUSIONS:
      Our findings confirm the high prevalence of glucose intolerance in the early
      postpartum period in women with previous GDM. PCOS emerges as a new strong
      antepartum predictor of prediabetes.

PMID- 24931702
TI  - Relationships between adipokines, biomarkers of endothelial function and
      inflammation and risk of type 2 diabetes.
AB  - AIMS: Identification of novel biomarkers of diabetes risk help to understand
      mechanisms of pathogenesis and improve risk prediction. Our objectives were to
      examine the relationships between adipokines, biomarkers of inflammation and
      endothelial function and development of type 2 diabetes; and to assess the
      relevance of including these biomarkers in type 2 diabetes prediction risk
      models. METHODS: 1345 subjects from the SU.VI.MAX study, who were free of
      diabetes at baseline and who completed 13 years of follow-up were included in the
      present analyses. Odds ratios (OR) with 95% confidence intervals (95% CI) of
      incident type 2 diabetes associated with a 1-SD increase in adiponectin, leptin,
      C-reactive protein (CRP), soluble intracellular adhesion modecule-1 (sICAM-1),
      soluble vascular cell adhesion molecule 1 (sVCAM-1), E-selectin and monocyte
      chemoattractant protein-1 (MCP-1) were estimated. Predicitive performances of
      models including biomarkers were assessed with area under the receiver operating
      curves (AUC) and integrated discrimination improvement (IDI) statistics. RESULTS:
      82 subjects developed type 2 diabetes during follow-up. The risk of developing
      type 2 diabetes increased with increasing concentrations of leptin (2.04
      (1.28;3.26)), sICAM-1 (1.39 (1.08;1.78)) and sVCAM-1 (1.29 (1.01;1.64)). Type 2
      diabetes associations with leptin remained significant after adjusting for a
      combination of biomarkers. Models adjusted for novel biomarkers had improved
      performance compared to models adjusted for classical risk factors as assessed by
      IDI, but not by AUC. CONCLUSIONS: Adipokines, biomarkers of inflammation and
      endothelial function were significantly associated to onset of type 2 diabetes.
      However their inclusion in predictive scores is not supported by the present
      study.

PMID- 24931703
TI  - Editorial comment.

PMID- 24931706
TI  - Interaction of early life stress and corticotropin-releasing hormone receptor
      gene: effects on working memory.
AB  - BACKGROUND: Early life stress (ELS) experience is associated with persisting
      working memory (WM) deficits; changes to the corticotropin-releasing hormone
      (CRH) system; and structural, functional, and epigenetic changes in the
      hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene
      interact with ELS experience to predict depression as well as neuroendocrine and
      neuronal reactivity. Although these findings indicate that vulnerable genotypes
      might also show impaired WM performance after ELS experience, no previous study
      investigated whether there is an interaction effect of CRHR1 polymorphisms and
      ELS experience on WM performance. METHODS: Subjects (N = 451) were genotyped for
      rs110402 and rs242924 within the CRHR1 gene. We used an n-back task to
      investigate the hypothesis that WM performance in healthy subjects may be subtly
      influenced by functional differences in CRHR1 and represents an early marker of
      increased vulnerability after exposure to ELS. RESULTS: Exposure to ELS had a
      particularly strong impact on WM performance in subjects with the common
      homozygous GG GG genotype, whereas only severe exposure to ELS interfered with WM
      accuracy in AT carriers. CONCLUSIONS: Our data indicate that specific CRHR1
      polymorphisms moderate the effect of ELS experience on WM performance. Exposure
      to ELS in combination with a vulnerable genotype results in subtle memory
      deficits in adulthood, which might develop before psychopathological symptoms.

PMID- 24931705
TI  - Restoring mood balance in depression: ketamine reverses deficit in dopamine
      dependent synaptic plasticity.
AB  - BACKGROUND: One of the most novel and exciting findings in major depressive
      disorder research over the last decade is the discovery of the fast-acting and
      long-lasting antidepressant effects of ketamine. Indeed, the therapeutic effects
      of classic antidepressants, such as selective serotonin reuptake inhibitors,
      require a month or longer to be expressed, with about a third of major depressive
      disorder patients resistant to treatment. Clinical studies have shown that a low
      dose of ketamine exhibits fast-acting relatively sustained antidepressant action,
      even in treatment-resistant patients. However, the mechanisms of ketamine action
      at a systems level remain unclear. METHODS: Wistar-Kyoto rats were exposed to
      inescapable, uncontrollable footshocks. To evaluate learned helplessness
      behavior, we used an active avoidance task in a shuttle box equipped with an
      electrical grid floor. After helplessness assessment, we performed in vivo
      electrophysiological recordings first from ventral tegmental area dopaminergic
      (DA) neurons and second from accumbens neurons responsive to fimbria stimulation.
      Ketamine was injected and tested on helpless behavior and electrophysiological
      recordings. RESULTS: We show that ketamine is able to restore the integrity of a
      network by acting on the DA system and restoring synaptic dysfunction observed in
      stress-induced depression. We show that part of the antidepressant effect of
      ketamine is via the DA system. Indeed, injection of ketamine restores a decreased
      dopamine neuron population activity, as well as synaptic plasticity (long-term
      potentiation) in the hippocampus-accumbens pathway, via, in part, activation of
      D1 receptors. CONCLUSIONS: This work provides a unique systems perspective on the
      mechanisms of ketamine on a disrupted limbic system.

PMID- 24931707
TI  - The large GTPase Mx1 is involved in apical transport in MDCK cells.
AB  - In epithelial cells apical proteins are transported by specific transport
      carriers to the correct membrane domain. The composition of these carriers is
      heterogeneous and comprises components such as motor proteins, annexins, lectins,
      Rab GTPases and cargo molecules. Here, we provide biochemical and fluorescence
      microscopic data to show that the dynamin-related large GTPase Mx1 is a component
      of post-Golgi vesicles carrying the neurotrophin receptor p75(NTR) . Moreover,
      siRNA-mediated depletion of Mx1 significantly decreased the transport efficiency
      of apical proteins in MDCK cells. In conclusion, Mx1 plays a crucial role in the
      delivery of cargo molecules to the apical membrane of epithelial cells. 

PMID- 24931708
TI  - Effects of multiple collections on spermatozoa quality of Persian sturgeon,
      Acipenser persicus: motility, density and seminal plasma composition.
AB  - In this study, we investigated the effects of multiple collections of sperm on
      the endangered Persian sturgeon, Acipenser persicus, in terms of a number of
      sperm functional parameters (percentage of motile spermatozoa, total time period
      of motility and sperm concentration) as well as on the ionic composition, protein
      concentration and osmolality of seminal plasma. Semen samples were collected from
      12 induced male fish in three experimental groups that had been injected
      intramuscularly with LHRH-A2, at dosages of 5 MUg/kg body weight, at a number of
      time regimes: at 12 h, 17 h and 24 h after spawning induction (1); at 24, 29 and
      34 h after spawning induction (2); and at 36, 41 and 46 h after spawning
      induction (3). The percentage of motile spermatozoa and the period of sperm
      motility decreased significantly (p < 0.05) after the second and third
      collections. The concentration of spermatozoa decreased after the third
      collection, but this decline was not significant. No significant effect of
      multiple collections on protein concentration and ionic content (with exception
      of the Cl(-) ion) of seminal plasma was observed. In all experimental groups, a
      moderate impact of sequential collection on the osmolality (p < 0.05) of seminal
      plasma was observed. This study provides new data on the effects of multiple
      collections on spermatological characteristics in the Persian sturgeon. Our
      results confirm that sequential stripping after the third collections has a
      negative effect on a number of functional parameters associated with sperm.

PMID- 24931709
TI  - Reliability of visual orienting response measures in children with and without
      visual impairments.
AB  - BACKGROUND: From the need for a quantitative method to examine visual processing
      in young children, we measured ocular orienting responses to visual stimuli
      (form, motion, expansion, color, contrast, cartoons). Reliability and
      applicability of this method were assessed. NEW METHOD: 80 children (1-12 years)
      with visual impairments and a reference group of 118 typically developing
      children (1-6 years) completed two sessions. Test-retest reliability was measured
      by calculating differences in reaction time and fixation accuracy between the two
      sessions. For applicability, the cumulative percentage of children that fell
      within a pre-defined reliability interval was plotted against the mean number of
      responses. RESULTS: In typically developing children none of the outcome measures
      significantly differed between sessions. In the children with visual impairments
      similar results were obtained, except for motion. This stimulus elicited
      significantly faster reaction times in the second session. In at least 80% of the
      children reliable reaction times could be calculated if 4 responses to a cartoon
      stimulus and 1 or 2 responses to the other stimuli were measured. COMPARISON WITH
      EXISTING METHOD(S): The existing method to quantify visual information processing
      has been refined: the range of visual functions was extended and a criterion for
      reliable assessment of orienting response times was established. CONCLUSIONS:
      Objective measurement of orienting responses is a reliable method to test the
      initial stage of visual processing in children with and without visual
      impairments. A set minimum number of responses for each stimulus warrants the
      reliability of measurements obtained with this functional method in clinical
      practice.

PMID- 24931710
TI  - A wavelet based algorithm for the identification of oscillatory event-related
      potential components.
AB  - Event related potentials (ERPs) are very feeble alterations in the ongoing
      electroencephalogram (EEG) and their detection is a challenging problem. Based on
      the unique time-based parameters derived from wavelet coefficients and the
      asymmetry property of wavelets a novel algorithm to separate ERP components in
      single-trial EEG data is described. Though illustrated as a specific application
      to N170 ERP detection, the algorithm is a generalized approach that can be easily
      adapted to isolate different kinds of ERP components. The algorithm detected the
      N170 ERP component with a high level of accuracy. We demonstrate that the
      asymmetry method is more accurate than the matching wavelet algorithm and t-CWT
      method by 48.67 and 8.03 percent, respectively. This paper provides an off-line
      demonstration of the algorithm and considers issues related to the extension of
      the algorithm to real-time applications. 

PMID- 24931711
TI  - High-density lipoprotein subfractions: current views and clinical practice
      applications.
AB  - High-density lipoprotein (HDL) is astonishingly complex, but the de facto
      standard for its measurement has been remarkably simple: total cholesterol
      content. It is time to prioritize higher-resolution HDL measurement techniques
      that capture better the biologically and clinically important characteristics of
      HDL. Scientific advances have ushered in a new era in which we view HDL in terms
      of its subfractions, particle structure, metabolism, and functional integration
      of its proteome and lipidome. HDL subfractions appear to be associated with
      function. In general, smaller, denser HDL3 is more tightly linked to favorable
      atheroprotective functions and clinical outcomes. Techniques to measure the
      cholesterol content or particle concentrations of HDL subfractions are available
      clinically. In the future, we anticipate subfractionating HDL based on its
      functional properties. 

PMID- 24931712
TI  - Pre-clinical functional Magnetic Resonance Imaging Part I: The kidney.
AB  - The prevalence of chronic kidney disease (CKD) is increasing worldwide. In Europe
      alone, at least 8% of the population currently has some degree of CKD. CKD is
      associated with serious comorbidity, reduced life expectancy, and high economic
      costs; hence, the early detection and adequate treatment of kidney disease is
      important. Pre-clinical research can not only give insights into the mechanisms
      of the various kidney diseases but it also allows for investigating the outcome
      of new drugs developed to treat kidney disease. Functional magnetic resonance
      imaging provides non-invasive access to tissue and organ function in animal
      models. Advantages over classical animal research approaches are numerous: the
      same animal might be repeatedly imaged to investigate a progress or a treatment
      of disease over time. This has also a direct impact on animal welfare and the
      refinement of classical animal experiments as the number of animals in the
      studies might be reduced. In this paper, we review current state of the art in
      functional magnetic resonance imaging with a focus on pre-clinical kidney
      imaging. 

PMID- 24931713
TI  - Osmotically driven formation of double emulsions stabilized by amphiphilic block
      copolymers.
AB  - Double emulsions are valuable for the formation of multi-compartmental
      structures. A variety of pathways to prepare double emulsions have been
      developed, but high-throughput routes to droplets of controlled size and
      architecture remain scarce. A new single-step process is introduced for
      preparation of water-in-oil-in-water double emulsions by a previously unexplained
      process of self-emulsification. We show that the origin of this process is the
      osmotic stress resulting from the presence of salt impurities within the
      amphiphilic block copolymers used for emulsion stabilization. Further, we utilize
      osmotically driven emulsification to tailor the structures of multiple emulsions,
      which upon solvent evaporation can yield multi-compartmental capsules or
      hierarchically structured porous films. 

PMID- 24931714
TI  - Early diagnosis of amyotrophic lateral sclerosis--a way forward?

PMID- 24931716
TI  - Chronic alcohol consumption alters periodontal health in rats.
AB  - BACKGROUND: The aim of this study was to assess the effects of chronic alcohol
      consumption on periodontitis development in rats. METHODS: Periodontal disease
      was experimentally induced by lipopolysaccharide (LPS; 2 mg/ml) injections into
      the gingival tissue around first upper and lower molar's neck, and into the
      interdental space between first and second molars. This protocol was repeated for
      6 weeks on days 1, 3, and 5 of each week. Chronic alcohol consumption was induced
      by 20% ethanol (EtOH) as the only liquid source during 4 months. RESULTS: Chronic
      alcohol consumption by itself increased alveolar bone loss and biological
      mediators of periodontal disease such as prostaglandin E2 (PGE2 ) content on
      gingival tissue, and inducible nitric oxide synthase activity plus PGE2 content
      in submandibular gland. Unexpectedly, alcohol consumption did not increase the
      damage evoked by the proved model of LPS injections for periodontitis induction.
      CONCLUSIONS: Results suggest 20% alcohol consumption during 4 months generates
      differential effects on oral health of rats, depending on its pathophysiological
      state: It would exacerbate the inflammatory condition when periodontal damage is
      absent, but it would not when damage is installed.

PMID- 24931717
TI  - Cardiovascular disease risk factors associated with depression among Korean
      adults with coronary artery disease and cerebrovascular disease.
AB  - OBJECTIVE: This study investigated the cardiovascular risk factors associated
      with depression among Korean adults with coronary artery disease (CAD) and
      cerebrovascular disease (CBVD). METHODS: A total of 487 coronary artery disease
      and 434 cerebrovascular disease subjects from the Fourth Korean National Health
      and Nutrition Examination Survey were analyzed according to sex using multiple
      logistic regression. RESULTS: The prevalence of depression was 21.7% in those
      with CAD and 25.5% in those with CBVD. The associated risk factors for depression
      were female sex (odds ratio [OR] 15.77; 95% confidence interval [CI], 2.44
      102.03, P = 0.004), less education (OR 7.09 and 10.36, 95% CI, 1.24-40.75, 1.86
      57.70 for an elementary and middle school education, respectively), and
      hypertension (OR 5.35; 95% CI, 1.48-19.40) in those with CAD and were female sex
      (OR 4.06, 95% CI, 1.12-14.76) and diabetes mellitus (OR 3.31, 95% CI, 1.36-8.05)
      in CBVD. These significant associations remained in males, but not in females in
      those with both CAD and CBVD. CONCLUSIONS: This study found the associations
      between hypertension and depression in those with CAD and diabetes mellitus and
      depression in those with CBVD in males, but not in females. Further studies are
      needed to explore the associated psychosocial factors of depression in those with
      different CAD kinds in females.

PMID- 24931715
TI  - SRT2104 extends survival of male mice on a standard diet and preserves bone and
      muscle mass.
AB  - Increased expression of SIRT1 extends the lifespan of lower organisms and delays
      the onset of age-related diseases in mammals. Here, we show that SRT2104, a
      synthetic small molecule activator of SIRT1, extends both mean and maximal
      lifespan of mice fed a standard diet. This is accompanied by improvements in
      health, including enhanced motor coordination, performance, bone mineral density,
      and insulin sensitivity associated with higher mitochondrial content and
      decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle
      mass in an experimental model of atrophy. These results demonstrate it is
      possible to design a small molecule that can slow aging and delay multiple age
      related diseases in mammals, supporting the therapeutic potential of SIRT1
      activators in humans. 

PMID- 24931718
TI  - Abstracts of the 2014 AWHONN Annual Convention, June 14-18, 2014, Orlando,
      Florida.

PMID- 24931719
TI  - STAT transcription factors in normal and cancer stem cells.
AB  - Signal transducer and activator of transcription proteins (STATs) play vital
      roles in the regulation of cellular proliferation and survival in normal
      hematopoietic cells, including hematopoietic stem cells. However, aberrant
      activation of STATs is commonly observed in a number of hematologic malignancies,
      and recent studies indicate that targeting of STATs may have therapeutic benefit
      in these diseases. Additional studies have provided greater understanding of the
      cells responsible for leukemia initiation, referred to as leukemia stem cells.
      Emerging evidence indicates that STATs are important in maintaining leukemia stem
      cells and represent a promising target for eradication of this dangerous cell
      population. Here we summarize what is known about normal hematopoietic stem cells
      and the origin of leukemic stem cells. We further describe the roles of STAT
      proteins in these cell populations, as well as current progress toward the
      development of novel agents and strategies for targeting the STAT proteins.

PMID- 24931721
TI  - Radicular pain followed by epidural blood patch.

PMID- 24931720
TI  - Midline craniofacial malformations with a lipomatous cephalocele are associated
      with insufficient closure of the neural tube in the tuft mouse.
AB  - BACKGROUND: Genetic variations affecting neural tube closure along the head
      result in malformations to the face and brain, posing a significant impact on
      health care costs and the quality of life. METHODS: We have established a mouse
      line from a mutation that arose spontaneously in our wild-type colony that we
      called tuft. Tuft mice have heritable midline craniofacial defects featuring an
      anterior lipomatous cephalocele. RESULTS: Whole-mount skeletal stains indicated
      that affected newborns had a broader interfrontal suture where the cephalocele
      emerged between the frontal bones. Mice with a cephalocele positioned near the
      rostrum also presented craniofacial malformations such as ocular hypertelorism
      and midfacial cleft of the nose. Gross and histological examination revealed that
      the lipomatous cephalocele originated as a fluid filled cyst no earlier than
      E14.5 while embryos with a midfacial cleft was evident during craniofacial
      development at E11.5. Histological sections of embryos with a midfacial cleft
      revealed the cephalic neuroectoderm remained proximal or fused to the frontonasal
      ectoderm about the closure site of the anterior neuropore, indicating a defect to
      neural tube closure. We found the neural folds along the rostrum of E9 to E10.5
      embryos curled inward and failed to close as well as embryos with exencephaly and
      anencephaly at later stages. Whole-mount in situ hybridization of anterior
      markers Fgf8 and Sonic hedgehog indicated closure of the rostral site was
      compromised in severe cases. CONCLUSION: We present a model demonstrating how
      anterior cranial cephaloceles are generated following a defect to neural tube
      closure and relevance to subsequent craniofacial morphogenesis in the tuft mouse.

PMID- 24931723
TI  - Microfluidic generation of composite biopolymer microgels with tunable
      compositions and mechanical properties.
AB  - To develop an understanding of the nature of complex, spatiotemporal interactions
      between cells and the extracellular matrix (ECM), artificial ECMs formed from
      hydrogels with a particular spectrum of properties are being developed at a rapid
      pace. We report the microfluidic generation of small, monodisperse composite
      agarose-gelatin hydrogel modules (microgel particles) that can be used for cell
      encapsulation and can serve as instructive cellular microenvironments. The
      agarose component of the microgels gelled under reduced temperature, while
      gelatin modified with phenolic hydroxyl groups underwent peroxidase-catalyzed
      gelation. Microgel composition, structure, morphology, and rigidity were tuned in
      a high-throughput manner. The results of this work are important for the
      generation of libraries of cell-laden polymer microgels for single-cell analysis,
      tissue engineering, and fundamental studies of the role of local
      microenvironments in cell fate. 

PMID- 24931722
TI  - Expression of two parental imprinted miRNAs improves the risk stratification of
      neuroblastoma patients.
AB  - Age at diagnosis, stage, and MYCN amplification are the cornerstones of the risk
      stratification score of neuroblastoma that enables defining patients at low- and
      high risk. Refinement of this stratification is needed to optimize standard
      treatment and to plan future clinical trials. We investigated whether two
      parental imprinted miRNAs (miR-487b and miR-516a-5p) may lead to a risk score
      with a better discrimination. Expression levels of maternal miR-487b and paternal
      miR-516a-5p were determined using quantitative RT-PCR both for 231 neuroblastoma
      tumors (derivation set) and 101 independent neuroblastoma tumors (validation
      set). Survival outcomes were overall survival (OS) and disease-free survival
      (DFS). Multivariable Cox models were developed from derivation set and their
      performance evaluated using Akaike's information criterion (AIC) (goodness-of
      fit) and time-dependent area under curves (discrimination). The selected model
      was validated using internal and external validation. The prognostic model
      including current prognostic factors plus miR-487b, miR-516a-5p, and interaction
      between two miRNAs was selected. Performance of this model was better in terms of
      both predictive ability (smallest AIC) and discrimination power (AUC close to
      0.70). This model identifies three risk groups: high (3), intermediate (2), and
      low (1). Hazard ratios (HR) across risk groups were HR2/1 = 6.3 (2.7-14.6), HR3/1
      = 14.8 (7.2-30.2) for OS and HR2/1 = 2.8 (1.5-5.4), HR3/1 = 7.2 (3.9-13.4) for
      DFS. The rank between these three risk groups was maintained and validated when
      performing internal and external validation. Expression of maternal miR-487b and
      paternal miR-516a-5p improves the risk stratification. This better discrimination
      at diagnosis is of clinical utility both for current and future treatments of
      neuroblastoma patients.

PMID- 24931724
TI  - Inhibitory effects of bortezomib on platelet aggregation in patients with
      multiple myeloma.
AB  - INTRODUCTION: Multiple myeloma (MM) therapy affects prothrombotic and
      anticoagulant processes. Patients receiving thalidomide, especially in
      combination with steroids, are at increased risk of venous thromboembolism (VTE),
      while the incidence of VTE on bortezomib is low. In vitro studies indicate that
      bortezomib causes a reduction in ADP-induced platelet aggregation. OBJECTIVES: To
      analyse the influence of bortezomib on platelet aggregation induced by various
      agonists in patients with MM. PATIENTS AND METHODS: A total of 30 patients
      (median age 57.5years) with relapsed/refractory MM receiving bortezomib-based
      regimens were analysed. Optical platelet aggregometry was performed with the
      agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The
      results from two groups: those treated with bortezomib and thalidomide (BT group,
      n=11) and those without thalidomide (B group, n=19) were analysed. RESULTS:
      During the second cycle, significantly decreased platelet aggregation was
      observed in the B group: 5MUM ADP (p=0.0285, day 1 versus 8); 3.5MUM ADP
      (p=0.0005, day 1 versus 8 and day 1 versus 11), collagen (p=0.0014, day 4 versus
      8, day 4 versus 11), 1.25mg/ml ristocetin (p=0.0017, day 1 versus 8 and day 1
      versus 11). Agonist-induced platelet aggregation tended to be reduced over time
      during the 1st cycle in group B. In the thalidomide group, significant platelet
      aggregation inhibition by collagen only was found. Transient reduction in
      platelet count was observed in all patients, but more prominently in group B.
      CONCLUSION: The inhibitory effects of prolonged exposure of bortezomib on
      platelet aggregation were demonstrated in relapsed/refractory MM patients, but
      antithrombotic activity of bortezomib should be clarified in further prospective
      studies.

PMID- 24931725
TI  - An integrated molecular dynamics, principal component analysis and residue
      interaction network approach reveals the impact of M184V mutation on HIV reverse
      transcriptase resistance to lamivudine.
AB  - The emergence of different drug resistant strains of HIV-1 reverse transcriptase
      (HIV RT) remains of prime interest in relation to viral pathogenesis as well as
      drug development. Amongst those mutations, M184V was found to cause a complete
      loss of ligand fitness. In this study, we report the first account of the
      molecular impact of M184V mutation on HIV RT resistance to 3TC (lamivudine) using
      an integrated computational approach. This involved molecular dynamics
      simulation, binding free energy analysis, principle component analysis (PCA) and
      residue interaction networks (RINs). Results clearly confirmed that M184V
      mutation leads to steric conflict between 3TC and the beta branched side chain of
      valine, decreases the ligand (3TC) binding affinity by ~7 kcal mol(-1) when
      compared to the wild type, changes the overall conformational landscape of the
      protein and distorts the native enzyme residue-residue interaction network. The
      comprehensive molecular insight gained from this study should be of great
      importance in understanding drug resistance against HIV RT as well as assisting
      in the design of novel reverse transcriptase inhibitors with high ligand efficacy
      on resistant strains. 

PMID- 24931726
TI  - Costly infidelity: low lifetime fitness of extra-pair offspring in a passerine
      bird.
AB  - Extra-pair copulation (EPC) is widespread in socially monogamous species, but its
      evolutionary benefits remain controversial. Indirect genetic benefit hypotheses
      postulate that females engage in EPC to produce higher quality extra-pair
      offspring (EPO) than within-pair offspring (WPO). In contrast, the sexual
      conflict hypothesis posits that EPC is beneficial to males but not to females.
      Thus, under the sexual conflict hypothesis, EPO are predicted to be no fitter
      than WPO. We tested these two hypotheses in a 12-year dataset with complete life
      history and pedigree information from an isolated island population of house
      sparrows (Passer domesticus). We compared fitness components of EPO and two types
      of WPO: (1) WPO from genetically polyandrous "unfaithful" mothers, and (2) WPO
      from genetically monogamous mothers. We found that all three groups of offspring
      had similar probabilities of hatching and nestling survival. Unexpectedly, EPO
      had the lowest probability of recruiting into the breeding population and the
      lowest lifetime reproductive output. Our results indicate that EPO incurred
      indirect genetic costs, rather than benefits, which is contrary to indirect
      benefit models. Importantly, the indirect costs we observed are also
      underappreciated in current sexual conflict models. Our results call for improved
      theoretical frameworks that incorporate indirect costs by extending current
      sexual conflict models. 

PMID- 24931727
TI  - A newly identified fatty alcohol oxidase gene is mainly responsible for the
      oxidation of long-chain omega-hydroxy fatty acids in Yarrowia lipolytica.
AB  - Nine potential (fatty) alcohol dehydrogenase genes and one alcohol oxidase gene
      were identified in Yarrowia lipolytica by comparative sequence analysis. All
      relevant genes were deleted in Y. lipolytica H222DeltaP which is lacking beta
      oxidation. Resulting transformants were tested for their ability to accumulate
      omega-hydroxy fatty acids and dicarboxylic acids in the culture medium. The
      deletion of eight alcohol dehydrogenase genes (FADH, ADH1-7), which may be
      involved in omega-oxidation, led only to a slightly increased accumulation of
      omega-hydroxy fatty acids, whereas the deletion of the fatty alcohol oxidase gene
      (FAO1), which has not been described yet in Y. lipolytica, exhibited a
      considerably higher effect. The combined deletion of the eight (fatty) alcohol
      dehydrogenase genes and the alcohol oxidase gene further reduced the formation of
      dicarboxylic acids. These results indicate that both (fatty) alcohol
      dehydrogenases and an alcohol oxidase are involved in omega-oxidation of long
      chain fatty acids whereby latter plays the major role. This insight marks the
      first step toward the biotechnological production of long-chain omega-hydroxy
      fatty acids with the help of the nonconventional yeast Y. lipolytica. The
      overexpression of FAO1 can be further used to improve existing strains for the
      production of dicarboxylic acids. 

PMID- 24931728
TI  - Near-infrared and fourier transform infrared chemometric methods for the
      quantification of crystalline tacrolimus from sustained-release amorphous solid
      dispersion.
AB  - The objective of the present research was to study the feasibility of using near
      infrared (NIR) and Fourier transform infrared (FTIR)-based chemometric models in
      quantifying crystalline and amorphous tacrolimus from its sustained-release
      amorphous solid dispersion (ASD). ASD contained ethyl cellulose, hydroxypropyl
      methyl cellulose, and lactose monohydrate as carriers, and amorphous form of
      tacrolimus in it was confirmed by X-ray powder diffraction. Crystalline physical
      mixture was mixed with ASD in various proportions to prepare sample matrices
      containing 0%-100% amorphous/crystalline tacrolimus. NIR and FTIR of the samples
      were recorded, and data were mathematically pretreated using multiple scattering
      correction, standard normal variate, or Savitzky-Golay before multivariate
      analysis, partial-least-square regression (PLSR), and principle component
      regression (PCR). The PLSR models were more accurate than PCR for NIR and FTIR
      data as indicated by low value of root-mean-squared error of prediction, standard
      error of prediction and bias, and high value of R(2). Additionally, NIR data
      based models were more accurate and precise than FTIR data models. In conclusion,
      NIR chemometric models provide simple and fast method to quantitate crystalline
      tacrolimus in the ASD formulation.

PMID- 24931729
TI  - Multilocus assessment of phylogenetic relationships in Alytes (Anura, Alytidae).
AB  - With the advent of large multilocus datasets, molecular systematics is
      experiencing very rapid progress, but important challenges remain regarding data
      analysis and interpretation. Midwife toads (genus Alytes) exemplify two of the
      most widespread problems for accurate phylogenetic reconstruction: discerning the
      causes of discordance between gene trees, and resolving short internodes produced
      during rapid, successive splitting events. The three species in subgenus
      Baleaphryne (A. maurus, A. dickhilleni and A. muletensis), the sister group to A.
      obstetricans, have disjunct and highly restricted geographical ranges, which are
      thought to result from old vicariant events affecting their common ancestor, but
      their phylogenetic relationships are still unresolved. In this study we re
      address the phylogeny of Alytes with a special focus on the relationships in
      Baleaphryne with a multilocus dataset including >9000 base pairs of mitochondrial
      DNA and four nuclear markers (3142bp) in all recognized taxa, including all
      subspecies of A. obstetricans. Both concatenation and species tree analyses
      suggest that A. muletensis, endemic to the Balearic island of Mallorca, is the
      sister taxon to a clade comprising the southeastern Iberian endemic A.
      dickhilleni and the North African A. maurus. This scenario is consistent with
      palaeogeological evidence associated with the fragmentation of the Betic-Rifean
      Massif, followed by the opening of the Strait of Gibraltar. On the other hand,
      analyses of intraspecific variation in A. obstetricans are inconclusive regarding
      relationships between major clades and conflict with current subspecific
      taxonomy. 

PMID- 24931730
TI  - How many genera and species of woolly monkeys (Atelidae, Platyrrhine, Primates)
      are there? The first molecular analysis of Lagothrix flavicauda, an endemic
      Peruvian primate species.
AB  - We sequenced COI and COII mitochondrial genes of 141 Neotropical woolly monkeys
      to provide new insights concerning their phylogeography and phylogenetic
      relationships. For the first time, eight individuals of the endemic and extremely
      rare Peruvian yellow-tailed woolly monkey (flavicauda) were sequenced at these
      genes and compared with other Lagothrix taxa (poeppigii, lagotricha, lugens and
      cana). There were four main results. (1) L. flavicauda showed a gene diversity of
      zero, whereas poeppigii and lugens showed high levels of gene diversity and
      lagotricha and cana showed more modest levels of gene diversity. The absence of
      gene diversity found for L. flavicauda strongly supports that it is one of the 25
      more endangered primates on earth; (2) Our genetic distance and phylogenetic
      analyses, which included many cases of genetic introgression and recent
      hybridization, suggest that all woolly monkeys could be included in one unique
      genus, Lagotrix, divided into two species: L. flavicauda and L. lagotricha. The
      last species is divided into at least four subspecies. Our molecular results
      agree with Fooden's (1963) classification, but do not support the classification
      proposed by Groves (2001). (3) Poeppigii was the first taxon within L. lagotricha
      to experience a mitochondrial haplotype diversification, while cana and
      lagotricha experienced more recent mitochondrial haplotype diversification; (4)
      Poeppigii and lagotricha were the taxa which showed the greatest evidence of
      population expansions in different Pleistocene periods, whereas lugens
      experienced a population declination in the last 25,000 YA. 

PMID- 24931731
TI  - Phylogenetic position of Guihaiothamnus (Rubiaceae): its evolutionary and
      ecological implications.
AB  - Guihaiothamnus (Rubiaceae) is an enigmatic, monotypic genus endemic to
      southwestern China. Its generic status has never been doubted because it is
      morphologically unique by having rosette habit, showy, long-corolla-tubed
      flowers, and multi-seeded indehiscent berry-like fruits. The genus has been
      postulated to be a relict in the broad-leaved forests of China, and to be related
      to the genus Wendlandia, which was placed in the subfamily Cinchonoideae and
      recently classified in the tribe Augusteae of the subfamily Dialypetalanthoideae.
      Using combined evidence from palynology, cytology, and DNA sequences of nuclear
      ITS and four plastid markers (rps16, trnT-F, ndhF, rbcL), we assessed the
      phylogenetic position of Guihaiothamnus in Rubiaceae. Our molecular phylogenetic
      analyses placed the genus deeply nested within Wendlandia. This relationship is
      corroborated by evidence from palynology and cytology. Using a relaxed molecular
      clock method based on five fossil records, we dated the stem age of Wendlandia to
      be 17.46 my and, the split between G. acaulis and related Wendlandia species in
      southwestern China to be 2.11mya. This young age, coupled with the derived
      position in Wendlandia, suggests an evolutionary derivation rather than an
      evolutionary relict of G. acaulis. Its rosette habit and large showy flowers,
      which are very distinctive from other Wendlandias, are interpreted as a result of
      recent rapid adaptation to rock and cliff habitats. 

PMID- 24931732
TI  - In situ expression and serum level of thymic stromal lymphopoietin in oral lichen
      planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of oral
      mucosa in which the CD8(+) T cell-mediated cytotoxicity is regarded as a major
      mechanism of pathogenesis. The main objective of this study is to investigate in
      situ expression and secretion of thymic stromal lymphopoietin (TSLP) in specimens
      and sera from patients with oral lichen planus. METHODS: Thirty-six patients with
      OLP and 35 donors enrolled in specimen and serum collection. Immunohistochemical
      method and immunofluorescence double-staining method were used to detect the
      expression of thymic stromal lymphopoietin and its receptor (TSLPR) together with
      CD8 in OLP specimens. Enzyme-linked immunosorbent assay (ELISA) was used to
      detect TSLP secretion. RESULTS: More TSLP- or TSLPR-positive cells showed in OLP
      specimens than in normal controls, and TSLP-positive cells were mainly in the
      epithelium, while TSLPR-positive cells mainly in the lamina propria. Furthermore,
      the number of TSLP-positive cells in the stratum basal was associated with the
      amount of mononuclear cells infiltrating in the lamina propria of OLP specimens.
      Among infiltrating mononuclear cells in the lamina propria, some CD8-positive
      cells also expressed TSLPR. The TSLP serum level of patients with OLP was
      significantly higher than of healthy donors, but there was no statistically
      difference between two clinical subtypes of OLP. CONCLUSIONS: Our findings
      provided the first evidence that TSLP may enroll in the pathology of OLP and the
      TSLP-TSLPR interaction may play an important role in it.

PMID- 24931733
TI  - A severity score for acute necrotizing encephalopathy.
AB  - OBJECTIVE: To develop a score that predicts the prognosis of children with acute
      necrotizing encephalopathy (ANE). METHOD: We retrospectively evaluated clinical
      variables and neurological outcome in two cohorts of children with ANE. Firstly,
      we developed the ANE severity score (ANE-SS) according to the clinical variables
      that correlated with neurological outcome in 41 children who were included in our
      previous reports in 2009. We then applied the scoring system to a second cohort
      of 32 patients who were newly collected in 2011. We investigated the correlation
      between the ANE-SS and neurological outcome in all 73 patients. RESULTS: In the
      first cohort, brain stem lesions on MRI and state of shock at onset were
      significantly correlated with outcome. Age over 48 months, elevated CSF protein,
      and low platelet counts tended to be correlated with outcome. No types of
      treatment were correlated with outcome. The developed ANE-SS ranged from 0 to 9
      points, with 3 points for existence of shock, 2 points for brain stem lesions, 2
      points for age over 48 months, 1 point for platelet count below 100,000/MUL, and
      1 point for CSF protein above 60 mg/dl. Patients were classed as low risk (ANE-SS
      0-1 points), medium risk (ANE-SS 2-4 points), or high risk (ANE-SS 5-9 points).
      ANE-SS was significantly correlated with outcome in the group of 73 patients.
      CONCLUSION: ANE-SS can be used to predict outcome in patients with ANE. More
      effective treatments need to be developed for high-risk patients.

PMID- 24931734
TI  - Uncovering the roles of oxygen vacancies in cation migration in lithium excess
      layered oxides.
AB  - A novel oxygen vacancy assisted transition metal (TM) diffusion mechanism is
      proposed for the first time to explain the near-surface phase transformation in
      lithium excess transition metal layered oxides. Oxygen vacancies and TM migration
      have been observed at nm scale spatial resolution by Scanning Transmission
      Electron Microscopy and Electron Energy Loss Spectroscopy. Formation of (dilute)
      oxygen vacancies and their roles in assisting transition metal ion diffusion were
      further investigated using first principles calculations. The activation barriers
      of TM diffusion in the presence of oxygen vacancies are drastically reduced and
      consistently in a reasonable range for room temperature diffusion. 

PMID- 24931735
TI  - Is ostension any more than attention?
AB  - According to natural pedagogy theory, infants are sensitive to particular
      ostensive cues that communicate to them that they are being addressed and that
      they can expect to learn referential information. We demonstrate that 6-month-old
      infants follow others' gaze direction in situations that are highly attention
      grabbing. This occurs irrespective of whether these situations include
      communicative intent and ostensive cues (a model looks directly into the child's
      eyes prior to shifting gaze to an object) or not (a model shivers while looking
      down prior to shifting gaze to an object). In contrast, in less attention
      grabbing contexts in which the model simply looks down prior to shifting gaze to
      an object, no effect is found. These findings demonstrate that one of the central
      pillars of natural pedagogy is false. Sensitivity to gaze following in infancy is
      not restricted to contexts in which ostensive cues are conveyed. 

PMID- 24931736
TI  - Papain-induced experimental pulmonary emphysema in male and female mice.
AB  - In papain-induced models of emphysema, despite the existing extensive description
      of the cellular and molecular aspects therein involved, sexual hormones may play
      a complex and still not fully understood role. Hence, we aimed at exploring the
      putative gender-related differences in lung mechanics, histology and oxidative
      stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally
      either saline (50 MUL) or papain (10 U/50 MUL saline) once a week for 2 weeks. In
      males papain increased lung resistive and viscoelastic/inhomogeneous pressures,
      static elastance, and viscoelastic component of elastance, while females showed
      higher static elastance and resistive pressure only. Both genders presented
      similar higher parenchymal cellularity and mean alveolar diameter, and less
      collagen-elastic fiber content and body weight gain than their respective
      controls. Increased functional residual capacity was more prominent in males.
      Female papain-treated mice were more susceptible to oxidative stress. Thus, male
      and female papain-exposed mice respond differently, which should be carefully
      considered to avoid confounding results.

PMID- 24931738
TI  - A patient with lupus miliaris disseminatus faciei treated successfully with a
      combination of oral metronidazole and topical tacrolimus.

PMID- 24931739
TI  - The utility of dual bioelectrical impedance analysis in detecting intra-abdominal
      fat area in obese patients during weight reduction therapy in comparison with
      waist circumference and abdominal CT.
AB  - An increase in intra-abdominal fat area (IAFA) is an essential component of
      metabolic syndrome (MetS). Waist circumference (WC) is not a precise measure of
      IAFA, and computed tomography (CT) is unsuitable for frequent monitoring. Here,
      we examined utility of a dual bioelectrical impedance analysis (Dual BIA) for
      measuring IAFA in obese patients during weight reduction. Fat distribution was
      measured by Dual BIA and CT in 100 obese outpatients. All fat areas including
      total, IAFA, and subcutaneous fat by Dual BIA were more closely correlated with
      those by CT than WC. Estimated IAFA by Dual BIA was significantly correlated with
      number of MetS components as well as CT, but WC was not. Furthermore, in 61 obese
      patients who received 6-month weight reduction therapy, estimated IAFA by Dual
      BIA showed an earlier and greater decrease as well as that by CT than WC and BMI.
      In addition, decrease in estimated IAFA by Dual BIA through weight reduction had
      a higher correlation with decrease in IAFA by CT, than WC. This study is the
      first to demonstrate that the change in estimated IAFA by Dual BIA was highly
      correlated with that in IAFA by CT during weight reduction therapy. Our findings
      also indicate that estimated IAFA by Dual BIA is, potentially, a better indicator
      of severity of MetS, cardiovascular risk factors, and effectiveness of weight
      reduction than WC, and equal to IAFA by CT. Estimated IAFA by Dual BIA may be
      useful for monitoring the effectiveness of weight reduction therapy in obese
      patients. 

PMID- 24931737
TI  - Src-homology 2 domain-containing tyrosine phosphatase 2 promotes oral cancer
      invasion and metastasis.
AB  - BACKGROUND: Tumor invasion and metastasis represent a major unsolved problem in
      cancer pathogenesis. Recent studies have indicated the involvement of Src
      homology 2 domain-containing tyrosine phosphatase 2 (SHP2) in multiple
      malignancies; however, the role of SHP2 in oral cancer progression has yet to be
      elucidated. We propose that SHP2 is involved in the progression of oral cancer
      toward metastasis. METHODS: SHP2 expression was evaluated in paired oral cancer
      tissues by using immunohistochemical staining and real-time reverse transcription
      polymerase chain reaction. Isogenic highly invasive oral cancer cell lines from
      their respective low invasive parental lines were established using a Boyden
      chamber assay, and changes in the hallmarks of the epithelial-mesenchymal
      transition (EMT) were assessed to evaluate SHP2 function. SHP2 activity in oral
      cancer cells was reduced using si-RNA knockdown or enforced expression of a
      catalytically deficient mutant to analyze migratory and invasive ability in vitro
      and metastasis toward the lung in mice in vivo. RESULTS: We observed the
      significant upregulation of SHP2 in oral cancer tissues and cell lines. Following
      SHP2 knockdown, the oral cancer cells markedly attenuated migratory and invasion
      ability. We observed similar results in phosphatase-dead SHP2 C459S mutant
      expressing cells. Enhanced invasiveness was associated with significant
      upregulation of E-cadherin, vimentin, Snail/Twist1, and matrix metalloproteinase
      2 in the highly invasive clones. In addition, we determined that SHP2 activity is
      required for the downregulation of phosphorylated ERK1/2, which modulates the
      downstream effectors, Snail and Twist1 at a transcript level. In lung tissue
      sections of mice, we observed that HSC3 tumors with SHP2 deletion exhibited
      significantly reduced metastatic capacity, compared with tumors administered
      control si-RNA. CONCLUSIONS: Our data suggest that SHP2 promotes the invasion and
      metastasis of oral cancer cells. These results provide a rationale for further
      investigating the effects of small-molecule SHP2 inhibitors on the progression of
      oral cancer, and indicate a previously unrecognized SHP2-ERK1/2-Snail/Twist1
      pathway that is likely to play a crucial role in oral cancer invasion and
      metastasis.

PMID- 24931740
TI  - Reference standard of penile size and prevalence of buried penis in Japanese
      newborn male infants.
AB  - The present study set forth the reference values for penile size and determined
      the prevalence of buried penis in Japanese full-term newborns. The stretched
      penile length was measured and the presence of buried penis was assessed at 1-7
      days of age in 547 Japanese full-term newborn infants born between 2008 and 2012
      in Tokyo. The stretched penile lengths were compared at 1-12 hours and 1-7 days
      of age in 63 infants and by two observers in 73 infants to estimate postnatal
      changes and interobserver variation, respectively. The mean stretched penile
      length was 3.06 cm (SD, 0.26; 95% confidence interval [CI], 3.04-3.08) and the
      mean ratio of penile length to body length was 6.24 * 100(-1) (SD, 0.55 * 100(
      1)), both of which were significantly smaller than those in Caucasian newborn
      infants. Buried penis was identified in 20 of 547 infants (3.7%; 95% CI, 2.1
      5.2%). The first measurements of penile length at 1-12 hours were significantly
      smaller than the next measurements at 1-7 days (95% CI of the difference, 0.22
      0.34). The 95% CI for the limits of agreement in the penile lengths measured by
      the two observers was -0.58 to -0.40 for the lower limit and 0.33 to 0.51 for the
      upper limit. These findings indicate that the penile length should be assessed
      after 24 hours of age by the reference standard of the same ethnicity for
      identifying micropenis and that buried penis is not uncommon in Japanese full
      term newborns.

PMID- 24931741
TI  - Sarcoidosis with bone marrow involvement.

PMID- 24931742
TI  - Lamellar cationic lipid-DNA complexes from lipids with a strong preference for
      planar geometry: A Minimal Electrostatic Model.
AB  - We formulate and analyze a minimal model, based on condensation theory, of the
      lamellar cationic lipid (CL)-DNA complex of alternately charged lipid bilayers
      and DNA monolayers in a salt solution. Each lipid bilayer, composed by a random
      mixture of cationic and neutral lipids, is assumed to be a rigid uniformly
      charged plane. Each DNA monolayer, located between two lipid bilayers, is formed
      by the same number of parallel DNAs with a uniform separation distance. For the
      electrostatic calculation, the model lipoplex is collapsed to a single plane with
      charge density equal to the net lipid and DNA charge. The free energy difference
      between the lamellar lipoplex and a reference state of the same number of free
      lipid bilayers and free DNAs, is calculated as a function of the fraction of CLs,
      of the ratio of the number of CL charges to the number of negative charges of the
      DNA phosphates, and of the total number of planes. At the isoelectric point the
      free energy difference is minimal. The complex formation, already favoured by the
      decrease of the electrostatic charging free energy, is driven further by the free
      energy gain due to the release of counterions from the DNAs and from the lipid
      bilayers, if strongly charged. This minimal model compares well with experiment
      for lipids having a strong preference for planar geometry and with major features
      of more detailed models of the lipoplex.

PMID- 24931743
TI  - Clinical outcome and prognostic factors after salvage surgery for isolated
      regional squamous cell carcinoma recurrences.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcome and predictive
      factors for salvage surgery of isolated regional recurrences of head and neck
      squamous cell carcinoma. METHODS: A retrospective study was conducted with 55
      patients who were treated with surgery-based treatment. RESULTS: The 5-year
      overall survival (OS) and disease-free survival (DFS) rates were 61.8% and 60%,
      respectively. Extracapsular spread (ECS) was an independent factor associated
      with worse disease-specific survival. The patients who had advanced N
      classification, ECS, and in-field recurrence had a significantly worse OS rate,
      whereas those with an initial DFS time of 6 months or more experienced better
      outcomes. CONCLUSION: Salvage surgery for isolated regional recurrence resulted
      in an acceptable oncologic outcome and mortality. Successful surgical salvage is
      most probable in late recurrence (>=6 months) patients with recurrent N1 stage
      tumors (no evidence of ECS) outside of the previous treatment field.

PMID- 24931744
TI  - Comparing primiparous and multiparous mothers in a nurse home visiting prevention
      program.
AB  - BACKGROUND: An important yet overlooked feature of prominent prevention programs
      serving expectant mothers is the exclusion of women with children. This study
      examines mothers (n = 3,260) participating in a program without parity exclusion
      criteria, and compares demographic characteristics, risk status, service use, and
      child maltreatment outcomes. METHODS: A longitudinal, prospective study comparing
      primiparous (n = 1,890) and multiparous (n = 1,370) mothers participating in a
      nurse home visiting program. Patient groups are compared using bivariate and
      multivariate methods. RESULTS: Comparison by parity shows multiparous mothers had
      higher cumulative risk scores and individual risk factors related to maternal and
      child health, behavioral health, and violence exposure. Multiparous mothers were
      more likely to seek out services themselves and to initiate services later in the
      postnatal period. A significant trend exists among more children and greater
      caregiver stress, maternal depression, and child maltreatment. Multivariate
      models indicate infants of multiparous mothers have a higher risk (hazard ratio =
      1.49) for later reports of child maltreatment. CONCLUSIONS: As compared with
      primiparous mothers, multiparous mothers were at higher risk but had similar
      levels of service use. Programs limited to primiparous mothers are missing a
      critical opportunity for prevention. Programs serving multiparous mothers should
      incorporate strategies to directly address caregiver stress and postpartum
      depression.

PMID- 24931745
TI  - Keteniminium ion-initiated cascade cationic polycyclization.
AB  - A novel and efficient keteniminium-initiated cationic polycyclization is
      reported. This reaction, which only requires triflic acid or bistriflimide as
      promoters, affords a straightforward entry to polycyclic nitrogen heterocycles
      possessing up to three contiguous stereocenters and seven fused cycles. These
      complex, polycyclic molecules can be obtained in a single operation from readily
      available ynamides which were shown to be remarkable building blocks for
      multiple, consecutive cationic transformations. 

PMID- 24931746
TI  - Malaria in pregnancy and irritable bowel syndrome.

PMID- 24931747
TI  - China rubra for side-effects of quinine: a prospective, randomised study in
      pregnant women with malaria in Cotonou, Benin.
AB  - BACKGROUND: In endemic areas, gestational malaria is responsible for low birth
      weight and maternal anaemia. Quinine is the reference treatment for acute malaria
      in pregnant women, irrespective of term. However, quinine administration is
      associated with various side-effects. We evaluated the impact of the homeopathic
      medicine China rubra 7CH on the side-effects of quinine used as treatment for
      acute malaria in pregnant women in Cotonou, Benin. METHODS: This prospective,
      comparative, randomised study was carried out between June and December 2007 in
      the Saint Jean-Baptiste Medical Centre, Cotonou. Women were included if they were
      >3 months pregnant and had a clinical diagnosis of malaria confirmed by a
      positive thick blood smear. The study population was divided into two groups: (i)
      patients who presented between the 1st and 15th of each month and who received
      China rubra 7CH plus quinine (China group); and (ii) patients who presented from
      the 16th to the end of each month and who received treatment with quinine only
      (Standard group). The aim was to compare the frequency of side-effects of quinine
      in the two groups until day 6 after the start of treatment. Neither the patients
      nor the care givers were blinded to study treatment. Statistical comparison of
      the two groups was carried out with an alpha risk fixed at 5%. RESULTS: 211 women
      were recruited: 105 received quinine plus China rubra 7CH (China group) and 106
      received quinine only (Standard group). A decrease in proportion of patients
      presenting with side-effects was observed in the China group from day 0 to day 6
      of follow-up (53.9%-23.3%) whereas the proportion of patients with side-effects
      in the Standard group did not change significantly (85.9% on day 0 vs. 82.5% on
      day 6). Ninety-six (72.4%) patients in the China group and 103 (97.2%) in the
      Standard group reported at least one side-effect during follow-up (p < 0.0001).
      The most frequently reported side-effects were tinnitus, dizziness and asthenia.
      CONCLUSIONS: This preliminary study shows the interest of China rubra 7CH in
      limiting the side-effects of quinine used for the treatment of acute malaria in
      pregnant women.

PMID- 24931748
TI  - Interim results of a randomised controlled trial of homeopathic treatment for
      irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a chronic condition for which there is no
      consensus on the optimum treatment. Gastroenterology problems are some of the
      most common conditions treated by homeopaths, yet few trials have explored the
      effectiveness of individualised homeopathic treatment for IBS. A three-armed
      trial was conducted which compared: usual care, homeopathic treatment plus usual
      care and supportive listening plus usual care. The primary outcome was change in
      irritable bowel symptom severity score between baseline and 26 weeks, calculated
      using ANCOVA. An interim ANCOVA adjusted for baseline IBS severity, age and
      employment status found no statistically significant difference between the three
      arms. However, a post-hoc test comparing homeopathic treatment plus usual care to
      usual care alone found a statistically significant difference in favour of
      homeopathic treatment. In addition, 62.5 percent of patients in the homeopathic
      treatment arm (compared to 25.0 percent of those in the usual care arm), achieved
      a clinically relevant change in irritable bowel symptom severity score, which
      indicates a promising effect for homeopathic treatment, though these results
      should be interpreted with caution due to the low number of participants in the
      study.

PMID- 24931749
TI  - Effect of an homeopathic complex on fatty acids in muscle and performance of the
      Nile tilapia (Oreochromis niloticus).
AB  - BACKGROUND: The homeopathic complex HomeoAqua Mega 3((r)) was designed to
      stimulate fish liver function resulting in enhanced lipid metabolism and improved
      overall performance. The effect of the complex in fatty acid compounds in the
      muscle tissues and the performance of Nile tilapia (O. niloticus) were evaluated.
      METHODS: A control diet with 40 mL of alcohol solution (30 degrees  Gay Lussac
      (GL) alcohol) per kg of feed and another diet with 40 mL/kg of the homeopathic
      complex were analysed in sex-reversed juvenile male Nile tilapia with mean
      initial weights of 89.54 g (+/-7.97) and 89.74 g (+/-8.83) and initial total mean
      lengths of 16.93 cm (+/-0.56) and 16.85 cm (+/-0.56) for the control and
      homeopathy-treated fish, respectively. Overall, 200 fish were distributed into 10
      water tanks, with 20 specimens in each 600 L tank, they were kept for 63 days.
      Monitoring of the water's physical and chemical parameters was performed.
      Additionally, the percentage chemical composition and the composition of the
      muscle tissue fatty acids were determined, and fish performance was evaluated.
      RESULTS: No significant differences (p > 0.05) were found between treatments with
      regard to the water's physical and chemical parameters, moisture, ashes, proteins
      of the Nile tilapia muscular tissue and mean rates of total weight and length of
      the animals in the final period of the assay. The total lipid (TL) rates of the
      tilapia muscle tissue were 1.133 +/- 0.2% at the start (control and homeopathy)
      and 0.908 +/- 0.14% (control) and 0.688 +/- 0.14% (homeopathy) at the end of the
      experiment (p < 0.06). The sum total of the SFAs (saturated fatty acids) was
      338.50 +/- 0.15 at the start (control and homeopathy) and 271.49 +/- 0.34 mg/g of
      the TLs for the control and 226.12 +/- 0.77 mg/g of TL for the homeopathy at the
      end of the experiment (p < 0.05). The n-6/n-3 ratio was also lower for the
      homeopathy-treated fish (8.45 +/- 0.40) compared with the control fish (9.60 +/-
      0.14), (p < 0.05) at the end of the 63-day period. CONCLUSION: Nile tilapia
      juveniles that received the HomeoAqua Mega-3((r)) in their diets had a decrease
      in the TL rates, mainly for the SFAs, and the n-6/n-3 ratio, compared with the
      control group, without any changes in the animal performance during the
      experimental period.

PMID- 24931751
TI  - Geographical and temporal distribution of basic research experiments in
      homeopathy.
AB  - The database HomBRex (Homeopathy Basic Research experiments) was established in
      2002 to provide an overview of the basic research already done on homeopathy
      (http://www.carstens-stiftung.de/hombrex). By this means, it facilitates the
      exploration of the Similia Principle and the working mechanism of homeopathy.
      Since 2002, the total number of experiments listed has almost doubled. The
      current review reports the history of basic research in homeopathy as evidenced
      by publication dates and origin of publications. In July 2013, the database held
      1868 entries. Most publications were reported from France (n = 267), followed by
      Germany (n = 246) and India (n = 237). In the last ten years, the number of
      publications from Brazil dramatically increased from n = 13 (before 2004) to n =
      164 (compared to n = 251 published in France before 2004, and n = 16 between 2004
      and 2013). The oldest database entry was from Germany (1832).

PMID- 24931750
TI  - Diverse biological effects of electromagnetic-treated water.
AB  - The effects of water treated with an electromagnetic field (EMF) were
      investigated on two biological systems, humans and plants. Purified de-ionised
      water was treated by (1) boiling, (2) exposure to microwave radiation, and (3)
      low frequency electromagnetic oscillation molecular resonance effect technology
      (MRET), before being used to prepare media for culturing human peripheral blood
      mononuclear cells (PBMC) from three healthy females. Our results indicated that
      PBMC culture in MRET-activated medium showed significantly less oxidative
      metabolism when compared to media prepared from other types of water. As for the
      effects on soybean, our results indicated that both MRET- and microwave-treated
      water greatly enhanced the length of the root. These results suggested that
      electromagnetic-treated water can have diverse biological effects on both animal
      and plant cells. Since these effects are related to the 'Memory of Water',
      hypothesis which has been suggested as an explanation of the action of high
      homeopathic dilutions, our finding warrant a further investigation on the
      mechanisms of various types of physically conditioned water on specific cellular
      activities.

PMID- 24931752
TI  - Observations on the effects of odours on the homeopathic response.
AB  - Samuel Hahnemann described incidences where the homeopathic response was
      disrupted by noxious smells in the environment. An earlier paper proposed that
      homeopathic medicines may be sensed by vomeronasal cells (VNCs) i.e. microvillus
      or brush cells in the vomeronasal organ (VNO), the taste buds and associated with
      the trigeminal nerve and nervus terminalis. This paper proposes an extension to
      the theory and suggests that a subset of solitary chemosensory cells (SCCs) in
      the diffuse chemosensory system (DCS) that is morphologically similar to VNCs
      might also be receptive to homeopathic medicines. The types of odours that may
      interfere with this process are described. Two clinical cases of disruption of
      the homeopathic response are given as examples, showing that successful re
      establishment of remedy action can be produced by timely repetition of the
      medicine. The ramifications on clinical homeopathic practice are discussed. 

PMID- 24931753
TI  - Observational study of Arctium lappa in the treatment of acne vulgaris.
AB  - INTRODUCTION: Arctium lappa (Lappa) is used in traditional Western and Chinese
      medicine for acne. It is mentioned in homeopathic literature for acne, but its
      effect has not previously been evaluated. OBJECTIVE: To determine the
      effectiveness of homeopathic medicine Lappa in treatment of acne vulgaris.
      METHODS: An uncontrolled observational interventional study was conducted on
      human subjects who fulfilled the inclusion criteria and gave written informed
      consent. Lappa was prescribed in potencies starting from 6c rising to 1M as
      required, over a period of 6 months. Objective assessment was change in acne
      lesion counts supplemented with Global Acne Grading System (GAGS) and subjective
      assessment by using Acne-Specific Quality of Life questionnaire (Acne-QoL).
      RESULTS: Out of 34 human subjects, 32 completed the follow-up. Statistical
      significant results were seen in lesion counts, GAGS and Acne-QoL score (p value
      <0.001). CONCLUSION: Lappa has shown positive effects in the treatment of acne
      especially of inflammatory type. Further controlled, randomized studies with
      larger sample size are desirable. Trial is registered at ClinicalTrials.gov
      Identifier: NCT01040390.

PMID- 24931754
TI  - Hahnemann and placebo.
AB  - Samuel Hahnemann (1755-1843) known today as the founder of homoeopathy, was - as
      far as we know - the first physician who administrated placebos to his patient on
      a systematic and regular basis. This study is based upon unpublished documents
      (e.g. patients' letters) in the Archives of the Institute for the History of
      Medicine of the Robert Bosch Foundation in Stuttgart. It also profited from the
      critical edition of Hahnemann's case journals and the editorial comments which
      have also been published in this series. Hahnemann differentiated clearly between
      homeopathic drugs and pharmaceutical substances which he considered as sham
      medicine (e.g. milk sugar). A close look at Hahnemann's case journals reveals
      that the percentage of placebo prescriptions was very high (between 54 and 85
      percent). In most instances Hahnemann marked placebos with the paragraph symbol
      (S). The rationale behind this practice was that Hahnemann had encountered the
      well-known problem that patients were used to taking medicine on a daily basis as
      it was typical for the age of heroic medicine. The main reason for giving placebo
      was therefore to please the impatient patient who was used to frequent
      medications in allopathic medicine, not only every day but sometimes also hourly.

PMID- 24931755
TI  - Parenteral immunonutrition in patients with acute pancreatitis: a systematic
      review and meta-analysis.
AB  - BACKGROUND & AIMS: Acute pancreatitis is a systemic immunoinflammatory response
      to auto-digestion of the pancrease and peri-pancreatic organs. Patients with
      acute pancreatitis can rapidly develop nutritional deficiency; hence nutritional
      support is important and critical. Sometimes parenteral nutrition (PN) is
      inevitable in acute pancreatitis. Due to immunosuppressive and inflammatory
      nature of the disease, it seems that immunonutrients like glutamine and omega-3
      fatty acids (omega-3 FAs) added to parenteral formulas may improve the
      conditions. We conducted a meta-analysis to evaluate the effects of parenteral
      immunonutrition on clinical outcomes (infectious complications, length of
      hospital stay (LOS) and mortality) in patients with acute pancreatitis. METHODS:
      A computerized literature search on four databases (PubMed, Cochrane, ISI Web of
      Science, and Iran Medex) was performed to find all the randomized controlled
      trials (RCTs) assessed the effects of parenteral immunonutrition in acute
      pancreatitis. Necessary data were extracted and quality assessment of RCTs was
      performed with consensus in the study team. Fixed effects model was used to
      conduct the meta-analysis. RESULTS: One hundred and ninety four references were
      found via our search in which 7 articles matched our criteria for enrolling the
      meta-analysis. Parenteral immunonutrition significantly reduced the risk of
      infectious complications (RR = 0.59; 95% CI, 0.39-0.88; p <= 0.05) and mortality
      (RR = 0.26; 95% CI, 0.11-0.59; p <= 0.001). LOS was also shorter in patients who
      received immunonutrition (MD = -2.93 days; 95% CI, -4.70 to -1.15; p <= 0.001).
      CONCLUSION: Immunonutrients like glutamine and omega-3 FAs added to parenteral
      formulas can improve prognoses in patients with acute pancreatitis.

PMID- 24931757
TI  - The role of Black fathers in the lives of children in South Africa: child
      protection for Black South Africans is often a collective responsibility.

PMID- 24931756
TI  - The influence of parenteral glutamine supplementation on glucose homeostasis in
      critically ill polytrauma patients--A randomized-controlled clinical study.
AB  - BACKGROUND & AIMS: Rapid onset of resistance to insulin is a prominent component
      of stress metabolism in multiple trauma patients. Recent studies have clarified
      the role of amino acids (especially glutamine) in glucose transportation and the
      benefits of parenteral alanyl-glutamine supplementation (0.3-0.6 g/kg/day) in
      glucose homeostasis. The aims of this study are to evaluate the incidence of
      hyperglycemic episodes and the need for exogenous insulin to maintain stable
      glucose levels in critically ill polytrauma patients supplemented with parenteral
      glutamine dipeptide (Dipeptiven((r))) versus standard nutritional support.
      METHODS: This was an open-label randomized-controlled trial of 82 polytrauma
      patients aged 20-60 years old, randomly assigned into two equal groups
      independent of sex, age and Injury Severity Score. We excluded patients with
      diabetes mellitus, or renal or hepatic failure. One group received parenteral
      Dipeptiven((r)) supplementation of 0.5 g/kg/day and the other received standard
      isocaloric isoproteinic nutritional support. RESULTS: We found that 63% of
      patients in the glutamine-supplemented group had no hyperglycemic episodes; only
      37% required exogenous insulin (mean daily requirement of 44 units/day). In the
      control group, 51% of patients required insulin (mean daily requirement 63
      unit/day; p = 0.0407). CONCLUSIONS: The effect of glutamine supplementation on
      glucose homeostasis is associated with a lower incidence of hyperglycemia among
      critically ill polytrauma patients, and leads to a lower mean daily dose of
      insulin. Controlled-trials.com Identifier: ISRCTN71592366 (http://www.controlled
      trials.com/ISRCTN71592366/ISRCTN71592366).

PMID- 24931758
TI  - Working with fathers to safeguard children: failure to work with fathers around
      the child occurs regularly.

PMID- 24931759
TI  - Byars two-stage procedure for hypospadias after urethral plate transection.
AB  - OBJECTIVE: To report on the outcomes of primary hypospadias repaired with the
      Byars two-stage procedure. MATERIALS AND METHODS: Primary hypospadias repairs
      with the Byars two-stage procedure, between 2009 and 2012, were retrospectively
      reviewed. Medical charts were reviewed and analyzed. Follow up was at two weeks,
      three months, six months and one year after surgery. Complications, which
      included fistula, glans dehiscence, meatal stenosis, urethral stricture,
      diverticulum, recurrent penile curvature and others, were documented and
      analyzed. RESULTS: One hundred and twenty-eight cases were included in the
      present study. The median follow up was 30 months (range 13-44 months). All flaps
      took successfully after the first stage. Overall complication rates were 11.8%.
      Complications included: seven cases of fistula; five glans dehiscence; two
      urethral strictures, which developed after fistula repair; and one concealed
      penis. No recurrent penile curvature was recorded. CONCLUSIONS: The Byars two
      stage procedure is an option for primary hypospadias when the urethral plate is
      transected. It had an 11.8% complication rate in this present study.

PMID- 24931760
TI  - Cytoarchitecture of the olfactory bulb in the laggard mutant mouse.
AB  - The laggard (lag) mutant mouse, characterized by hypomyelination and cerebellar
      ataxia, is a spontaneously occurring mutant mouse caused by mutation in the Kif14
      gene. In this mutant mouse, the laminated structures such as the cerebral and
      cerebellar cortices and the dentate gyrus are cytoarchitecturally abnormal.
      Macroscopically, the olfactory bulb of the lag mutant mouse is smaller in size
      and more transparent than the normal counterpart. Hematoxylin-eosin staining
      reveals that the mutant olfactory bulb has normal lamination in general, but
      detailed analysis has demonstrated that olfactory periglomerular cells and
      granule cells are reduced in number. In the mutant, olfactory glomeruli are
      cytoarchitecturally disorganized and mitral cells are arranged in multiple cell
      layers instead of being arranged in a single layer. The rostral migratory stream
      in the mutant becomes gradually thinner or obliterated during early postnatal
      days. Some of mitral cells and periglomerular cells are multinucleated,
      suggesting that Kif14 mutation leads to an abnormal cell division. In the mutant,
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive
      cells in the subventricular zone of the lateral ventricle are increased in
      number, especially at perinatal age, suggesting that the decreased population of
      granule cells in the lag mutant mouse is caused by the increased apoptotic cell
      death. The olfactory input appears to be intact, as indicated by anterograde
      labeling of olfactory nerves with an injection of wheat germ agglutinin
      horseradish peroxidase (WGA-HRP) into the olfactory mucosa. In conclusion, the
      olfactory bulb of the lag mutant mouse is cytoarchitecturally affected,
      suggesting that the causal gene for lag mutation, i.e., Kif14, has multiple
      effects on the development of laminated structures in the central nervous system
      in addition to the myelin formation. 

PMID- 24931761
TI  - Temporal modulation of the canonical clockwork in the suprachiasmatic nucleus and
      olfactory bulb by the mammary pheromone 2MB2 in pre-visual rabbits.
AB  - During the early stages of development, the olfactory system plays a vital role
      in the survival of altricial mammals. One remarkable example is the Oryctolagus
      cuniculus, whose mother-young interaction greatly depends on the 2-methylbut-2
      enal (2MB2) pheromone that triggers nipple search and grasping behaviors.
      Olfactory stimulation with 2MB2 regulates the expression of the core body
      temperature and locomotor activity rhythms in rabbit pups, indicating the
      modulation of the circadian system by this volatile cue. To address this issue,
      in the present study, we determined the effect of stimulation with pulses of 2MB2
      on the molecular circadian clockwork in the suprachiasmatic nucleus (SCN) and in
      the main olfactory bulb (MOB). For this purpose, 7-day-old rabbits were
      stimulated with distilled water (CON), with ethyl isobutyrate (ETHYL) or with the
      pheromone (2MB2) at different times of the cycle, and 1h later, the expression of
      the activity marker C-FOS and of the clock proteins PER1, CRY1 and BMAL1 was
      evaluated in the SCN and in the three layers of the MOB. The clock proteins were
      abundantly expressed in both structures; nevertheless these showed diurnal
      rhythmicity only in the MOB, confirming that central pacemakers exhibit a
      heterochronical development of the molecular clockwork. C-FOS expression in the
      SCN and in the MOB was modulated by exposure to ETHYL and to 2MB2 only when these
      stimulants were presented at ZT00 and at ZT18. In contrast, the clock proteins
      were essentially modulated by 2MB2 at ZT00 and at ZT06 in both structures. In
      addition, the PER1 and CRY1 proteins exhibited differential responses to
      stimulation in the three layers of the MOB. For the first time, we report a
      modulatory and time-dependent effect of the mammary pheromone 2MB2 on the
      expression of the core clock proteins in the SCN and in the MOB in rabbits during
      pre-visual stages of development. 

PMID- 24931762
TI  - The effect of motor imagery with specific implement in expert badminton player.
AB  - Motor skill can be improved with mental simulation. Implements are widely used in
      daily life and in various sports. However, it is unclear whether the utilization
      of implements enhances the effect of mental simulation. The present study was
      designed to investigate the different effects of motor imagery in athletes and
      novices when they handled a specific implement. We hypothesize that athletes have
      better motor imagery ability than novices when they hold a specific implement for
      the sport. This is manifested as higher motor cortical excitability in athletes
      than novices during motor imagery with the specific implement. Sixteen expert
      badminton players and 16 novices were compared when they held a specific
      implement such as a badminton racket and a non-specific implement such as a a
      plastic bar. Motor imagery ability was measured with a self-evaluation
      questionnaire. Transcranial magnetic stimulation was used to test the motor
      cortical excitability during motor imagery. Motor-evoked potentials (MEPs) in the
      first dorsal interosseous (FDI) and extensor carpi radialis muscles were
      recorded. Athletes reported better motor imagery than novices when they held a
      specific implement. Athletes exhibited more MEP facilitation than novices in the
      FDI muscle with the specific implement applied during motor imagery. The MEP
      facilitation is correlated with motor imagery ability in athletes. We conclude
      that the effects of motor imagery with a specific implement are enhanced in
      athletes compared to novices and the difference between two groups is caused by
      long-term physical training of athletes with the specific implement. 

PMID- 24931763
TI  - Changes of motor-cortical oscillations associated with motor learning.
AB  - Motor learning results from practice but also between practice sessions. After
      skill acquisition early consolidation results in less interference with other
      motor tasks and even improved performance of the newly learned skill. A specific
      significance of the primary motor cortex (M1) for early consolidation has been
      suggested. Since synchronized oscillatory activity is assumed to facilitate
      neuronal plasticity, we here investigate alterations of motor-cortical
      oscillations by means of event-related desynchronization (ERD) at alpha (8-12 Hz)
      and beta (13-30 Hz) frequencies in healthy humans. Neuromagnetic activity was
      recorded using a 306-channel whole-head magnetoencephalography (MEG) system. ERD
      was investigated in 15 subjects during training on a serial reaction time task
      and 10 min after initial training. The data were compared with performance during
      a randomly varying sequence serving as control condition. The data reveal a
      stepwise decline of alpha-band ERD associated with faster reaction times
      replicating previous findings. The amount of beta-band suppression was
      significantly correlated with reduction of reaction times. While changes of alpha
      power have been related to lower cognitive control after initial skill
      acquisition, the present data suggest that the amount of beta suppression
      represents a neurophysiological marker of early cortical reorganization
      associated with motor learning.

PMID- 24931764
TI  - Cajal-Retzius cells: update on structural and functional properties of these
      mystic neurons that bridged the 20th century.
AB  - Cajal-Retzius cells (CRc) represent a mostly transient neuronal cell type
      localized in the uppermost layer of the developing neocortex. The observation
      that CRc are a major source of the extracellular matrix protein reelin, which is
      essential for the laminar development of the cerebral cortex, attracted the
      interest in this unique cell type. In this review we will (i) describe the
      morphological and molecular properties of neocortical CRc, with a special
      emphasize on the question which markers can be used to identify CRc, (ii)
      summarize reports that identified the different developmental origins of CRc,
      (iii) discuss the fate of CRc, including recent evidence for apoptotic cell death
      and a possible persistence of some CRc, (iv) provide a detailed description of
      the electrical membrane properties and transmitter receptors of CRc, and (v)
      address the role of CRc in early neuronal circuits and cortical development.
      Finally, we speculate whether CRc may provide a link between early network
      activity and the structural maturation of neocortical circuits. 

PMID- 24931765
TI  - Over-expression of laminin correlates to recovery of vasogenic edema following
      status epilepticus.
AB  - In the present study, we addressed the question of whether the up-regulation of
      laminin expression represents the astroglio-vascular responses to status
      epilepticus (SE) in the rat brain to better understand the role of vasogenic
      edema in epileptogenic insult. In the hippocampus, vasogenic edema was observed
      in the hippocampus 12h after SE when astroglial degeneration was undetected.
      Vasogenic edema in the hippocampus was more severe in the CA1 region where
      astroglial loss was absent than in the dentate gyrus showing astroglial
      degeneration. In the piriform cortex (PC), vasogenic edema was accompanied by
      appearance of astroglial degeneration 12h after SE. Laminin expression in the
      hippocampus and the PC was increased 3 days and 4 days after SE, respectively.
      Laminin expression was up-regulated in the hippocampus and the PC with
      concomitant reduction of SMI-71 (the endothelial barrier antigen) expression.
      Four weeks after SE, laminin expression was reduced in vessels showing strong SMI
      71 expression within vasogenic edema lesion. Inhibition of SE-induced vasogenic
      edema formation by BQ788 effectively prevented laminin over-expression.
      Therefore, our findings indicate that laminin over-expression may be one of
      consequences from vasogenic edema rather than astroglial loss, and that laminin
      over-expression may promote migration of astrocytes to damaged or newly generated
      vessels to repair brain-blood barrier (BBB) disruption accompanied by the
      reconstruction of endothelial barrier.

PMID- 24931766
TI  - The heterogeneity of ventral tegmental area neurons: Projection functions in a
      mood-related context.
AB  - The ventral tegmental area (VTA) in the brain's reward circuitry is composed of a
      heterogeneous population of dopamine, GABA, and glutamate neurons that play
      important roles in mediating mood-related functions including depression. These
      neurons project to different brain regions, including the nucleus accumbens
      (NAc), the medial prefrontal cortex (mPFC), and the amygdala. The functional
      understanding of these projection pathways has been improved since the extensive
      use of advanced techniques such as viral-mediated gene transfer, cell-type
      specific neurophysiology and circuit-probing optogenetics. In this article, we
      will discuss the recent progress in understanding these VTA projection-specific
      functions, focusing on mood-related disorders. 

PMID- 24931767
TI  - Brain CD47 expression in a swine model of intracerebral hemorrhage.
AB  - CD47 contributes to neuronal death, inflammation and angiogenesis after brain
      ischemia. The role of CD47 in intracerebral hemorrhage (ICH) has not been
      investigated and the current study examined brain CD47 expression in a pig ICH
      model. Pigs received a blood injection or needle insertion into the right frontal
      lobe and were euthanized at different times to examine CD47 expression. Pigs were
      also treated with an iron chelator, deferoxamine, (50mg/kg, i.m.) or vehicle and
      killed at day-3 to examine the effects on CD47. ICH resulted in upregulation of
      brain CD47 in both white and gray matter by both immunohistochemistry and Western
      blot. A time-course showed ICH-induced CD47 upregulation from 4h to day-14, with
      a peak at day-3. CD47 positive cells were neurons, microglia/macrophage and
      oliogodendrocytes. Brain CD47 levels were lower in the ipsilateral white and gray
      matter in pigs which had deferoxamine treatment. In conclusion, CD47 expression
      was increased in the perihematomal white and gray matter after ICH. Deferoxamine
      and iron may modulate CD47 expression. 

PMID- 24931768
TI  - GILZ: Glitzing up our understanding of the glucocorticoid receptor in
      psychopathology.
AB  - Dysfunction of the hypothalamic-pituitary-adrenal axis, particularly the
      glucocorticoid receptor, is a commonly implicated link between stress and
      psychopathology. GR abnormalities are frequently reported in depression, and
      these anomalies must be resolved before depressive symptoms remit. This
      biological finding is rendered clinically relevant by the knowledge that only
      select antidepressants alter GR function. The relationship between GR dysfunction
      and other diseases associated with psychiatric stress, such as post-traumatic
      stress disorder (PTSD) and fibromyalgia, is also documented. However, as
      laboratory constraints limit the utility of GR testing, other measures of GR
      activity, such as levels of GR-induced genes, may have greater clinical value. In
      this review, glucocorticoid-induced leucine zipper (GILZ), a product of GR
      initiated gene transcription, will be discussed in the context of GR dysfunction
      in psychopathology. 

PMID- 24931769
TI  - Should the Emergency Journey Coordinator and 4 h target be introduced to others?

PMID- 24931770
TI  - Gluteal fold flap in perineal reconstruction for Crohn's disease-associated
      fistulae.
AB  - INTRODUCTION: Crohn's disease is increasing in incidence worldwide. It is
      associated with many complications including fistulae, which may require surgical
      intervention. Occasionally, formal perineal reconstruction is needed for
      extensive or definitive fistula surgery. Reconstruction for inflammatory disease
      presents unique challenges and often calls for innovative solutions. Gluteal fold
      flaps (GFFs), which have been widely used in vulvo-vaginal malignancy and
      anorectal cancer surgery, have not hitherto been reported for Crohn's disease
      associated fistulae. CASE PRESENTATION: A 30-year-old female presented with a 5
      year history of Crohn's-associated perianal and rectovaginal fistulae. She had a
      previous small bowel resection and ileostomy. A laparascopic pan-proctocolectomy
      was carried out followed by perineal reconstruction in a single stage procedure
      using a pedicled fasciocutaneous GFF. Seven months postoperatively, revisional
      surgery was carried out using the contralateral GFF due to two areas of
      persistent wound dehiscence. The outcome was complete resolution of the fistulae,
      stable wound closure and good cosmesis. DISCUSSION & CONCLUSION: This case
      demonstrates that it is practical to use the GFF for perineal reconstruction
      following excision of complex Crohn's-associated fistulae. The flap avoids the
      sequelae associated with sacrifice of regional muscle flaps and specifically
      circumvents the unavailability of the rectus abdominis flap in slim patients or
      those with in-situ ileostomies. It is easy and quick to raise and does not
      require an intra-operative change in the patient's position. The GFF ensured well
      vascularised skin cover, adequate flap volume with no loss of function and low
      donor site morbidity.

PMID- 24931771
TI  - Trends of melanoma presentation in Hull and East Yorkshire: 25 years of data
      (1988-2012).

PMID- 24931772
TI  - Distally-based osteocutaneous dorsal metatarsal artery flap for hallux
      reconstruction.
AB  - Reconstruction of complex defects of the distal portion of the foot remains a
      challenging problem for plastic surgeons. A traumatic case is presented where
      reconstruction of a complex plantar defect of the hallux was achieved using a
      distally-based osteocutaneous metatarsal artery flap based on the second dorsal
      metatarsal artery. Local flap repair is a viable reconstructive option for
      complex defects of the plantar surface of the forefoot. 

PMID- 24931773
TI  - The use of continuous external tissue expander for direct closure of
      anterolateral thigh free flap donor sites.

PMID- 24931774
TI  - Recent developments in gold(I) coordination chemistry: luminescence properties
      and bioimaging opportunities.
AB  - The fascinating biological activity of gold coordination compounds has led to the
      development of a wide range of complexes. The precise biological action of such
      species is often poorly understood and the ability to map gold distribution in
      cellular environments is key. This article discusses the recent progress in
      luminescent Au(I) complexes whilst considering their utility in bioimaging and
      therapeutics.

PMID- 24931775
TI  - The metal tin promoted cascade reaction of ketones in aqueous media for the
      construction of 2-bromo-4-aryl-1,3-pentadiene.
AB  - A novel type of transformation was discovered serendipitously during the Barbier
      type allenylation reaction of aromatic ketones promoted by the metal, tin, in
      aqueous media. Additionally, a series of new, highly functionalized 2-bromo-4
      aryl-1,3-pentadienes could be obtained with good yields in this reaction. This
      cascade reaction shows the unique properties of the metal, tin. Furthermore, it
      is actually a cascade reaction which involves two steps: one is the Barbier-type
      allenylation of the carbonyl compound, and the other is an SN2' type addition
      elimination reaction. Notably, this reaction has the advantages of simple, mild
      conditions and is easy to operate. Furthermore, the corresponding product could
      be applied to various coupling reactions or other diversified transformations. 

PMID- 24931776
TI  - Reinforcement enhances vigilance among children with ADHD: comparisons to
      typically developing children and to the effects of methylphenidate.
AB  - Sustained attention and reinforcement are posited as causal mechanisms in
      Attention-Deficit/Hyperactivity Disorder (ADHD), but their interaction has
      received little empirical study. In two studies, we examined the impact of
      performance-based reinforcement on sustained attention over time, or vigilance,
      among 9- to 12-year-old children. Study 1 demonstrated the expected vigilance
      deficit among children with ADHD (n = 25; 12% female) compared to typically
      developing (TD) controls (n = 33; 22% female) on a standard continuous
      performance task (CPT). During a subsequent visit, reinforcement improved
      attention more among children with ADHD than controls. Study 2 examined the
      separate and combined effects of reinforcement and acute methylphenidate (MPH) on
      CPT performance in children with ADHD (n = 19; 21% female). Both reinforcement
      and MPH enhanced overall target detection and attenuated the vigilance decrement
      that occurred in no-reinforcement, placebo condition. Cross-study comparisons
      suggested that the combination of MPH and reinforcement eliminated the vigilance
      deficit in children with ADHD, normalizing sustained attention. This work
      highlights the clinically and theoretically interesting intersection of
      reinforcement and sustained attention.

PMID- 24931777
TI  - Predictors of quality of life in 102 patients with treated Cushing's disease.
AB  - OBJECTIVE: To identify predictors for quality of life (QoL) in treated Cushing's
      disease (CD) and quantify patients' assessment of their disease status. CONTEXT:
      Significant reductions in QoL exist in CD patients despite treatment. Identifying
      predictors of QoL is paramount to the long-term management of these patents.
      DESIGN: A cross-sectional study was conducted of patients with treated CD.
      Patients completed a medical history questionnaire and three validated quality of
      life assessments: Cushing's QoL Questionnaire (CushingQoL), Hospital Anxiety and
      Depression Scale (HADS) and Nottingham Health Profile (NHP). PATIENTS: 102
      patients (75.7% female, mean time since surgery 7.4 years) with treated CD were
      included. MEASUREMENTS: Patients were categorized by biochemical and self
      identified disease status. Mean CushingQoL, anxiety and depression scores were
      compared by unpaired t-tests. Multiple linear regressions were performed on the
      whole cohort to assess for predictors of impaired QoL. RESULTS: Ninety-two per
      cent of the cohort met criteria for biochemical remission, but only 80.4% felt
      they had achieved remission. Among those with biochemical remission, those who
      also self-identified as being in remission had higher CushingQoL scores than
      those who self-identified as having persistent disease (P = 0.042). Anxiety (P =
      0.032) and depression (P = 0.018) scores were lower, and CushingQoL scores were
      higher (P = 0.05) in patients who self-identified as being in remission compared
      to persistence. Recovery time, BMI, gender and age were also predictors for QoL.
      CONCLUSION: Our study identifies the discordance that can exist between
      biochemical and self-assessed disease status and demonstrates its impact on QoL
      in patients with CD. These findings highlight the importance of incorporating
      patients' disease perceptions in their management.

PMID- 24931779
TI  - Editorial.

PMID- 24931780
TI  - Problems of research on pharmacotherapy of rapidly cycling bipolar disorder.

PMID- 24931778
TI  - Predictors of medium-term patency in percutaneous endovascular therapy of femoro
      popliteal lesions.
AB  - BACKGROUND: The objective is to study the medium-term results of angioplasty and
      stenting in the femoro-popliteal sector in patients with critical limb ischemia
      (CLI), and identify angiographic predictive factors of primary patency. PATIENTS
      AND METHODS: Retrospective review of 98 patients with critical ischemia and
      angiographic lesions characterized as TASC A=13 (14%), B=38 (40%), C=24 (25%) or
      D=20 (21%). A total of 106 angioplasties and primary self-expanding stents (mean
      length of stent coverage of 19cm) were performed between January 2006 and January
      2011. RESULTS: The immediate results of patency, limb salvage and survival were
      95, 96 and 96%, respectively. Primary patency at 1 and 2 years was 54 and 38%,
      respectively. Twenty-seven cases (25%) required endovascular iterative
      procedures, providing an assisted patency at 1 and 2 years of 72 and 60%, and a
      secondary patency of 80 and 67%. A lower primary patency was observed (log rank)
      when stent length was >20cm (P<.001), popliteal artery was invloved (P=.004), and
      in TASC C and D lesions (P=.04). In multivariate analysis (Cox), only stent
      length>20cm was an independent negative predictor for primary patency (HR=5.7,
      P<.001). The limb salvage at 1 and 2 years was 83 and 81%, respectively.
      CONCLUSIONS: Angioplasty with stent in the femoro-popliteal sector is a safe
      technique, but with significantly lower permeability results in injuries that
      require stent coverage of more than 20cm. In these cases, vein bypass surgery
      should be the procedure of choice.

PMID- 24931781
TI  - Can we identify the factors influencing the burden on family members of patients
      with schizophrenia?
AB  - A growing number of studies reflects an increasing growing interest in the burden
      on the family (BF) of sufferers from schizophrenia. Many of these studies aim at
      revealing and identifying the variables that determine BF. This review compares
      and discusses the results of these studies. Although many variables, such as the
      diagnosis and symptoms of the patient, the duration of the illness, the treatment
      setting (outpatient/inpatient), the family relationship between the patient and
      the relative, and the type of family intervention (counselling and psycho
      education) are examined in various studies, there is little consensus on which
      factors determine the extent and/or pattern of BF. In our opinion, this lack of
      consistency is mainly caused by: (1) the varieties of definitions and
      operationalizations of BF employed; (2) the fact that most studies examine only
      one or just a few variables, so that variables other than those examined may have
      varied between studies; and (3) the difference in the periods of time discussed
      in the different studies. To gain more insight into the factors that determine
      BF, a better standardization of the definition and operationalization of BF, as
      well as of the period of time studied, is needed, as well as exhaustive studies
      examining the various factors that may determine BF. 

PMID- 24931782
TI  - Hypnosis as an intervention in pain management: A brief review.
AB  - While there is a consensus that psychosocial factors play an important role in
      the experience of pain, clinical interventions for acute and chronic pain remain
      primarily biomedical. This pattern persists despite a body of recent empirical
      work supporting the effectiveness of a number of behavioral and relaxation
      interventions for these problems. One of these interventions is hypnosis. We
      briefly discuss hypnotic analgesia and describe how hypnosis can be integrated
      into biomedical treatment for acute and chronic pain. Special attention is given
      to indications and contraindications, preparation of patients, and technique. 

PMID- 24931783
TI  - Acute antidepressant response to fluoxetine and sertraline in psychiatric
      outpatients with psychomotor agitation.
AB  - INTRODUCTION: Sertraline and fluoxetine have different pharmacologic and
      pharmacokinetic profiles, which may be of clinical relevance in the determination
      of treatment response in different subtypes of depression. OBJECTIVE: To analyse
      the efficacy of sertraline and fluoxetine in a subgroup of 78 patients with
      evidence of significant psychomotor agitation (HAM-D item 8 &#104 1 and HAM-D
      item 9 &#83 2 at study entry) in a 6-week study comparing sertraline (50 - 100
      mg/day) and fluoxetine (20 - 40 mg/day) for the treatment of major depression in
      286 psychiatric outpatients. RESULTS: The proportion of patients with psychomotor
      agitation responding ( &#83 50% reduction HAM-D score) at last visit was
      significantly ( P < 0.05) higher in the sertraline group than in the fluoxetine
      group (62% vs 39%, respectively). Most of the secondary efficacy parameters
      showed significantly ( P &#104 0.05) greater improvement in the sertraline
      treatment group at last visit: HAM-D &#104 8, HAM-D total score, HAM-D
      anxiety/somatization factor, HAM-D weight factor, HAM-A total score, CGI-S,
      Raskin Depression score, and Covi Anxiety score. CONCLUSION: The findings of this
      retrospective data analysis suggest that fluoxetine may be a less efficacious
      antidepressant than sertraline in patients with psychomotor agitation.

PMID- 24931784
TI  - The Wessex Suicide Audit 1988-1993: A study of 1457 suicides with and without a
      recent psychiatric contact.
AB  - INTRODUCTION: The inquest files of 1457 suicides from a defined geographical area
      were inspected to establish their psychiatric patient status at the time. METHOD:
      Risk factors significantly more prevalent in recent psychiatric patient (RPP)
      suicides than in other suicides were determined. (RPPs were psychiatric patients
      who died before discharge, within a year of discharge from inpatient care, or
      within a year of last contact with a specialist psychiatric service). RESULTS:
      Significant differences were found between the RPP suicides and other suicides in
      causes of death, drugs used in fatal overdose, clinical characteristics and time
      since contact with a medical practitioner, particularly with a GP. RPPs were
      significantly ( P < 0.01) more likely to have: had a family history of mental
      illness; attempted suicide in the previous 6 months; made a suicide threat in the
      previous month; died from an overdose of prescribed medication; shown symptoms of
      depression; and been in contact with a doctor in the preceding week. CONCLUSION:
      The similarity of the RPP and other suicides in Wessex to those in both national
      and international suicide populations suggest that the findings may be generally
      applicable.

PMID- 24931785
TI  - Effect of executive functioning on perceived needs in chronic schizophrenia.
AB  - INTRODUCTION: Recent approaches to needs assessment involve patients in this
      process; however, little is known of the effects of mental illness on patients'
      ability to assess their own needs. METHOD: The needs of 26 subjects with
      schizophrenia were assessed over 22 domains by patients and staff, using the
      Camberwell Assessment of Need Short Appraisal Schedule (CANSAS). Patients'
      executive functioning was assessed using the Wisconsin Card Sorting Test (WCST).
      RESULTS: Mean discrepancies between ratings by staff and by patients were
      compared across executive functioning; results showed no effect of executive
      functioning on the discrepancy between staff and patient ratings. Higher
      executive functioning was associated with more met needs. Multivariate analysis
      showed higher executive functioning associated with more needs in some but not
      all areas. CONCLUSIONS: Results suggest that patients with schizophrenia and
      impaired executive functioning can validly estimate their needs. Better executive
      functioning may be associated with the ability to get one's needs met, increased
      awareness of needs, better ability to communicate needs, or more needs in certain
      areas. Need is shown to be a complex variable, and not simply an index of
      functioning. Hospitals and clinics must ensure that patients' views find full
      expression in ratings. Needs ratings and rehabilitation status should be viewed
      in the light of neuropsychological functioning.

PMID- 24931786
TI  - Discharge prescribing practices: Comparing a research ward to general treatment
      wards.
AB  - OBJECTIVE: To compare the prescribing practices between a research ward and
      general non-research wards within the same psychiatric facility. METHOD: This
      drug utilization survey is a retrospective naturalistic study evaluating
      discharge prescriptions from a tertiary-care psychiatric teaching hospital over a
      2-year period. RESULTS: Overall, patients discharged from the general wards were
      prescribed significantly more psychotropic medications than patients discharged
      from the research ward. This was attributed, in part, to the greater prevalence
      of antipsychotic polypharmacy and anticholinergic utilization. CONCLUSIONS: We
      postulate that the academic environment of a research ward accounts for the
      differences in prescribing practices observed in our study.

PMID- 24931787
TI  - A preliminary study of patients on repeat prescriptions of opioid and non-opioid
      analgesics.
AB  - BACKGROUND: Available literature suggests that problems due to dependence do not
      result from the use of low doses of low-potency opioids used for short periods of
      time, but no studies looked at the effect of their long-term use. OBJECTIVES: The
      main objective of the study was to discover whether those patients on long-term
      low-potency opioids, and those on non-opioid analgesics, could suffer the
      problems of tolerance and dependence. The study also explored the validity of
      applying DCR-10 criteria to a non-problematic population of analgesic users in
      identifying drug-dependent patients in primary care. METHOD: The prevalence of
      potential dependence amongst long-term users was assessed by a semi-structured
      questionnaire applying the DCR-10 criteria for Dependence Syndrome. The sample
      consisted of 38 randomly selected patients, drawn from four practices in North
      Cheshire, who had been on continuous repeat prescriptions of low-potency opioids,
      compound analgesics containing them and non-opioid analgesics (non-steroidal anti
      inflammatory drugs - NSAIDs) for a minimum of one year, without any problems
      becoming apparent either to the patients or to their GPs. RESULTS: Approximately
      3.6% of the North Cheshire GP practice population, predominantly elderly people,
      were shown to be on either opioid and/or non-opioid analgesics continuously for
      at least one year. An estimated 31% and 40% of patients on NSAIDs and low-potency
      opioids respectively fulfilled the DCR-10 criteria for Dependence Syndrome. With
      the exception of the criterion of 'impaired control' (odds ratio 4; P < 0.05),
      the DCR-10 criteria are equally likely to be reported in both groups. CONCLUSION:
      An unexpectedly high incidence of dependence was found, not only on opioids but
      also within the NSAIDs group. The findings may have resulted, at least in part,
      from an undetermined DCR-10 specificity.

PMID- 24931788
TI  - Johann Bernhard Aloys von Gudden (1824-1886): not only the King of Bavaria's
      psychiatrist.
AB  - The great achievements of Bernhard von Gudden in the field of biological
      psychiatry are overshadowed by his two-day treatment of the Bavarian 'fairy-tale'
      king Ludwig II, with whom he drowned in the Lake of Starnberg in 1886. Gudden was
      in fact a visionary psychiatrist who blended a strong interest in neurobiology
      with humanitarian principles. He was far more than just a consulting psychiatrist
      to the Bavarian royal family. 

PMID- 24931789
TI  - The Charles Bonnet syndrome: symptomatic relief with atypical neuroleptics: a
      case series.
AB  - We describe a consecutive case series of five patients who all fulfil published
      criteria for Charles Bonnet syndrome. Four of the five patients showed a good
      response to the atypical antipsychotic sulpiride. The nature of the Charles
      Bonnet syndrome is briefly reviewed. 

PMID- 24931790
TI  - Pisa syndrome (pleurothotonus) in a polytoxicomanic patient.
AB  - We describe the case of a 33-year-old drug addict who developed Pisa syndrome
      (pleurothotonus) following an intoxication with tramadol, alprazolam, diazepam,
      bromazepam, alcohol and dothiepin. Pisa syndrome abated as the patient recovered
      from his intoxication. We discuss the possible causes of Pisa syndrome and
      suggest that high doses of the tricyclic antidepressant dothiepin might be the
      most appropriate explanation for the appearance of Pisa syndrome in this patient.

PMID- 24931791
TI  - 'Alice in Wonderland' syndrome as a precursor of delusional misidentification
      syndromes.
AB  - The present paper describes a case of abuse of toluene-based solvent in which
      features of both 'Alice in Wonderland' (AIW) syndrome with deja vu , and
      delusional misidentification syndromes (DMS), were exhibited. Toluene-induced
      brain dysfunction was the basis of the weak ties between percepts and sensory
      information, which in turn led to the misperceptions. Once misperceptions fed
      back into the cycle comprised of misperceptions, false beliefs and erroneous
      expectations, DMS were induced. AIW syndrome with deja vu is a precursor and
      forms the basis of DMS. 

PMID- 24931794
TI  - D-cycloserine injected into the dorsolateral periaqueductal gray induces
      anxiolytic-like effects in rats.
AB  - D-cycloserine (DCS) is a partial agonist of the glycine site coupled to the NMDA
      receptor (NMDAR). As a consequence, depending on the doses used it can function
      as an agonist or antagonist at this site. In rodents, anxiolytic-like effects
      have been observed after the systemic administration of high doses of DCS. The
      brain sites of these effects have not been investigated. Direct brain injection
      of glycine site antagonists or agonists into the dorsolateral periaqueductal gray
      (dlPAG), a brain structure involved in the modulation of defensive-related
      behaviors, produces anxiolytic- or anxiogenic-like effects, respectively. The
      present study investigated if the dlPAG could be a brain site of the anxiolytic
      effects observed after DCS systemic administration. Male Wistar rats received
      intra-dlPAG injections of DCS (25, 50, 100 or 200 nmol) and were exposed to the
      elevated plus-maze (EPM) or to the light-dark box. DCS, at the dose of 200 nmol,
      increased open arm exploration and the time spent in the light compartment,
      respectively. Based on this result we tested the effects of intra-dlPAG DCS (200
      nmol) administration in animals submitted to the Vogel conflict tests. Anxiolytic
      like effect was also observed in this test indicated by the increase of punished
      responses. The drug did not change locomotor activity, discarding potential
      confounding factors. These results indicated that administration of DCS, a
      partial agonist of the NMDAR-associated glycine site, into the dlPAG induces
      anxiolytic-like effects in different models, pointing to a possible site of
      action of this compound.

PMID- 24931795
TI  - The role of alpha oscillations for illusory perception.
AB  - Alpha oscillations are a prominent electrophysiological signal measured across a
      wide range of species and cortical and subcortical sites. Alpha oscillations have
      been viewed for a long time as an "idling" rhythm, purely reflecting inactive
      sites. Despite earlier evidence from neurophysiology, awareness that alpha
      oscillations can substantially influence perception and behavior has grown only
      recently in cognitive neuroscience. Evidence for an active role of alpha for
      perception comes mainly from several visual, near-threshold experiments. In the
      current review, we extend this view by summarizing studies showing how alpha
      defined brain states relate to illusory perception, i.e. cases of perceptual
      reports that are not "objectively" verifiable by distinct stimuli or stimulus
      features. These studies demonstrate that ongoing or prestimulus alpha
      oscillations substantially influence the perception of auditory, visual or
      multisensory illusions. 

PMID- 24931797
TI  - Different relations between schedule-induced polydipsia and impulsive behaviour
      in the Spontaneously Hypertensive Rat and in high impulsive Wistar rats:
      questioning the role of impulsivity in adjunctive behaviour.
AB  - Rats belonging to three different strains (15 Wistar, 8 Spontaneously
      Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible
      relationship between different levels of impulsivity and development of schedule
      induced polydipsia (SIP). We first measured the rats' levels of impulsivity by
      means of delay-discounting and indifference-point procedures. Secondly,
      development of SIP was studied under a series of fixed time 15, 30, 60 and 120s
      food schedules, which were counterbalanced by means of a Latin-square design.
      Finally, we re-assessed the rats' levels of impulsivity by replicating the delay
      discounting test. The findings showed that, starting from equivalent levels of
      impulsivity, development of SIP differed among the groups of rats. In comparison
      with the rest of the animals, the SHRs were observed to attain elevated drinking
      rates under SIP. On the other hand, the Wistar rats which had initial high
      impulsivity levels similar to those of the SHRs, displayed the lowest rates of
      induced drinking. Moreover, low levels of impulsivity in Wistar rats prior to SIP
      acquisition were reflected into high drinking rates. Relation of SIP and
      impulsivity is questioned by present results, which gives ground to the
      understanding of the behavioural mechanisms involved in adjunctive behaviour and
      its usefulness as an animal model of excessive behaviour. 

PMID- 24931796
TI  - The action of orexin B on passive avoidance learning. Involvement of
      neurotransmitters.
AB  - The extensive projection of orexigenic neurons and the diffuse expression of
      orexin receptors suggest that endogenous orexins are involved in several
      physiological functions of the central nervous system, including learning and
      memory. Our previous study demonstrated that orexin A improves learning,
      consolidation and retrieval processes, which involves alpha- and beta-adrenergic,
      cholinergic, dopaminergic, GABA-A-ergic, opiate and nitrergic neurotransmissions.
      However, we have little evidence about the action of orexin B on memory processes
      and the underlying neuromodulation. Therefore, the aim of the present study was
      to investigate the action of orexin B on passive avoidance learning and the
      involvement of neurotransmitters in this action in rats. Accordingly, rats were
      pretreated with the selective orexin 2 receptor (OX2R) antagonist, EMPA; the
      gamma-aminobutyric acid subunit A (GABA-A) receptor antagonist, the bicuculline;
      a D2, D3, D4 dopamine receptor antagonist, haloperidol; the nonselective opioid
      receptor antagonist, naloxone; the non-specific nitric oxide synthase (NOS)
      inhibitor, nitro-l-arginine; the nonselective alpha-adrenergic receptor
      antagonist, phenoxybenzamine and the beta-adrenergic receptor antagonist,
      propranolol. Our results demonstrate that orexin B can improve learning,
      consolidation of memory and retrieval. EMPA reversed completely the action of
      orexin B on memory consolidation. Bicuculline blocked fully; naloxone, nitro-l
      arginine, phenoxybenzamine and propranolol attenuated the orexin B-induced memory
      consolidation, whereas haloperidol was ineffective. These data suggest that
      orexin B improves memory functions through OX2R and GABA-ergic, opiate,
      nitrergic, alpha- and beta-adrenergic neurotransmissions are also involved in
      this action. 

PMID- 24931798
TI  - 'His nerves gave way': Shell shock, history and the memory of the First World War
      in Britain.
AB  - During the First World War soldiers suffered from a wide range of debilitating
      nervous complaints as a result of the stresses and strains of modern warfare.
      These complaints--widely known as shell shock--were the subject of much medical
      military debate during the war and became emblematic of the war and its
      sufferings afterwards. One hundred years after the war the diagnosis of PTSD has
      not resolved the issues initially raised by First World War shell shock. The
      stigma of mental illness remains strong and it is still difficult to commemorate
      and remember the mental wounds of war in a culture which tend to glory or
      glamorise military heroes.

PMID- 24931799
TI  - Opportunities for utilizing new technologies to increase vaccine confidence.
AB  - The emergence of new digital technologies has 'disrupted' traditional vaccine
      information communication. This article reviews the impact of the Internet,
      social media, digital detection and mobile applications on both fueling anti
      vaccine sentiment and providing a mechanism by which to address vaccine
      hesitancy. While the anti-vaccine community has leveraged the Internet and social
      media to bypass traditional sources of information and communicate with
      susceptible parents, digital surveillance and mobile apps offer an important
      opportunity for public health officials to develop new strategies to identify and
      address concerns in a real-time manner. 

PMID- 24931800
TI  - Lipid trafficking in plant cells.
AB  - Plant cells contain unique organelles such as chloroplasts with an extensive
      photosynthetic membrane. In addition, specialized epidermal cells produce an
      extracellular cuticle composed primarily of lipids, and storage cells accumulate
      large amounts of storage lipids. As lipid assembly is associated only with
      discrete membranes or organelles, there is a need for extensive lipid trafficking
      within plant cells, more so in specialized cells and sometimes also in response
      to changing environmental conditions such as phosphate deprivation. Because of
      the complexity of plant lipid metabolism and the inherent recalcitrance of
      membrane lipid transporters, the mechanisms of lipid transport within plant cells
      are not yet fully understood. Recently, several new proteins have been implicated
      in different aspects of plant lipid trafficking. While these proteins provide
      only first insights into limited aspects of lipid transport phenomena in plant
      cells, they represent exciting opportunities for further studies. 

PMID- 24931801
TI  - Determination of ASP3258, a novel phosphodiesterase type 4 inhibitor, in rat
      plasma by high-performance liquid chromatography with fluorescence detection and
      its application to pharmacokinetic study.
AB  - The potent phosphodiesterase 4 inhibitor ASP3258 contains a carboxylic acid
      moiety and a naphthyridine ring and is a novel therapeutic agent for asthma and
      chronic obstructive pulmonary disease. To support the drug development of
      ASP3258, we developed and validated a simple method for its determination in rat
      plasma. Following the addition of the analog AS1406604-00 as an internal
      standard, plasma samples were processed using C18 -bonded solid-phase extraction
      cartridges under acidic conditions and injected into a high-performance liquid
      chromatography system with fluorescence detection. Chromatographic separation was
      achieved on a Shiseido Capcell Pak C18 UG120 column (3.0 * 150 mm, 5 um) with a
      mobile phase consisting of acetonitrile-0.5% acetic acid (50:50, v/v). HPLC
      eluent was monitored with a fluorescence detector set at a wavelength of 315 nm
      for excitation and 365 nm for emission. The calibration curve was linear over a
      range of 2.5-250 ng/mL. Validation data demonstrated that the method is
      selective, sensitive and accurate. In addition, the present method was
      successfully applied to rat plasma samples from a pharmacokinetic study.

PMID- 24931802
TI  - Compensatory hypertrophy after partial and radical nephrectomy in adults.
AB  - PURPOSE: We assessed compensatory hypertrophy in the contralateral kidney after
      partial and radical nephrectomy in adults. We also examined predictive factors to
      facilitate more accurate estimation of global renal function after surgery.
      MATERIALS AND METHODS: We analyzed the records of 172 patients who underwent
      partial or radical nephrectomy with appropriate studies to determine function and
      parenchymal mass specifically in the operated and contralateral kidneys. All
      patients required renal scans to provide split renal function preoperatively and
      postoperatively. Parenchymal volume was measured by computerized tomography. All
      studies were done less than 2 months preoperatively and 4 to 12 months
      postoperatively. RESULTS: A total of 113 and 59 patients underwent partial and
      radical nephrectomy, and median tumor size was 3.5 and 7.0 cm, respectively (p
      <0.0001). Of patients treated with partial nephrectomy 19% had high complexity
      tumor compared to 80% of those treated with radical nephrectomy (p <0.0001).
      Median ipsilateral parenchymal volume was reduced 18% after partial nephrectomy
      and the median glomerular filtration rate in this kidney decreased 24.4%. The
      median contralateral kidney function increase after partial nephrectomy was 2.3%
      vs 21.1% after radical nephrectomy (p <0.0001). Median global function decreased
      9.6% after partial nephrectomy vs 32.2% after radical nephrectomy (p <0.0001). A
      larger percent parenchymal volume loss (p = 0.0001) and fewer comorbidities (p =
      0.0072) significantly correlated with greater compensatory hypertrophy in the
      contralateral kidney on multivariable analysis. CONCLUSIONS: Compensatory
      hypertrophy in adults was limited after partial nephrectomy and it correlated
      significantly with the amount of parenchymal volume excised. Healthier patients
      also appeared to respond better. These results may allow for more accurate
      estimation of global renal function after partial and radical nephrectomy.

PMID- 24931803
TI  - Current clinical presentation and treatment of localized prostate cancer in the
      United States.
AB  - PURPOSE: SEER recently released patient Gleason scores at biopsy/transurethral
      resection of the prostate. For the first time this permits accurate assessment of
      prostate cancer presentation and treatment according to clinical factors at
      diagnosis. MATERIALS AND METHODS: We used the SEER database to identify men
      diagnosed with localized prostate cancer in 2010 who were assigned NCCN((r)) risk
      based on clinical factors. We identified sociodemographic factors associated with
      high risk disease and analyzed the impact of these factors along with NCCN risk
      on local treatment. RESULTS: Of the 42,403 men identified disease was high,
      intermediate and low risk in 38%, 40% and 22%, respectively. On multivariate
      analysis patients who were older, nonwhite, unmarried or living in a county with
      a higher poverty rate were more likely to be diagnosed with high risk disease
      (each p <0.05). Of the 38,634 men in whom prostate cancer was the first
      malignancy 23% underwent no local treatment, 40% were treated with prostatectomy,
      36% received radiation therapy and 1% underwent local tumor destruction,
      predominantly cryotherapy. On multivariate analysis patients who were older,
      black, unmarried or living in a county with a higher poverty rate, or who had low
      risk disease were less likely to receive local treatment (each p <0.05).
      CONCLUSIONS: Our analysis provides information on the current clinical
      presentation and treatment of localized prostate cancer in the United States.
      Nonwhite and older men living in a county with a higher poverty rate were more
      likely to be diagnosed with high risk disease and less likely to receive local
      treatment.

PMID- 24931804
TI  - Diabetes mellitus is independently associated with an increased risk of mortality
      in patients with clear cell renal cell carcinoma.
AB  - PURPOSE: Conflicting data exist on the interaction of diabetes mellitus with
      outcomes in patients with renal cell carcinoma. We evaluated the association of
      diabetes mellitus with survival in patients with clear cell renal cell carcinoma
      treated with nephrectomy. MATERIALS AND METHODS: We reviewed the records of 1,964
      patients treated surgically for sporadic, unilateral, M0 clear cell renal cell
      carcinoma between 1990 and 2008. One pathologist re-reviewed all specimens to
      confirm clear cell renal cell carcinoma. We matched 257 patients with diabetes
      1:2 to referent patients without diabetes according to clinicopathological and
      surgical features. Cancer specific and overall survival was estimated using the
      Kaplan-Meier method. Cox models were used to evaluate associations with outcomes.
      RESULTS: A total of 257 patients (13%) had diabetes mellitus. They were
      significantly older and more likely to be obese, and had higher Charlson scores,
      renal impairment and smoking rates, and worse performance status at surgery (p
      <0.001). Pathological features were similar between the groups. Median
      postoperative followup was 8.7 years. Five-year cancer specific survival was
      similar in patients with and without diabetes (82% vs 86%, p = 0.1) while 5-year
      overall survival was significantly worse in those with diabetes (65% vs 74%, p
      <0.001). On multivariable analysis diabetes mellitus independently predicted
      cancer specific mortality (HR 1.55, 95% CI 1.08-2.21, p = 0.02) and all-cause
      mortality (HR 1.32, 95% CI 1.06-1.64, p = 0.01). CONCLUSIONS: Our results suggest
      that diabetes mellitus is independently associated with decreased cancer specific
      and overall survival in patients with surgically treated clear cell renal cell
      carcinoma.

PMID- 24931805
TI  - Following the needles: an anatomical study to evaluate the postoperative safety
      and symptoms of patients receiving a transobturator male sling implant.
AB  - PURPOSE: Implanting a transobturator male sling is a valid option to manage
      urinary incontinence after prostatectomy. We evaluated the trajectory of Argus
      TTM needles blindly introduced into the retropubic space to determine the safety
      and etiology of postoperative symptoms that can arise from this implant.
      MATERIALS AND METHODS: Needles were implanted and perineal dissection was
      performed in 20 fixed, adult human male cadavers. The distance was measured from
      the upper and lower extremities of the needles in the internal pelvic wall up to
      the obturator neurovascular bundle. Anatomical variations identified in this area
      proximal to the needles were characterized. The inguinocrural region was also
      dissected from the needles positioned there. Statistical analysis of the results
      was done. RESULTS: All needles transfixed the obturator internus muscle. Of the
      needles 90% were completely immersed in its fibers and not visible in the inner
      wall of the pelvis. The distance to the obturator neurovascular bundle and
      anatomical variations were noted. In the inguinocrural region the pectineus and
      adductor longus muscles were perforated in all cadavers. CONCLUSIONS: The needle
      sling implant preserves the obturator neurovascular bundle and obviates the
      potential for postoperative pelvic hematoma. The anatomical trajectory of the
      needles used for this implant account for the groin and perineal pain side
      effects. Based on similarities between the Argus T and other types of outside-in
      transobturator male slings the results of the current study could be extrapolated
      to the latter slings.

PMID- 24931806
TI  - An observational analysis of provider adherence to AUA guidelines on the
      management of benign prostatic hyperplasia.
AB  - PURPOSE: We retrospectively evaluated urologist adherence to the AUA guidelines
      on the management of new patients with benign prostatic hyperplasia related lower
      urinary tract symptoms in a large university urology group. MATERIALS AND
      METHODS: All first time benign prostatic hyperplasia/lower urinary tract symptom
      visits to the urology clinic at the Northwestern Medical Faculty Foundation
      between January 1, 2008 and December 31, 2012 were evaluated using an
      institutionally managed electronic medical record data repository. Clinical
      documentation and orders from each encounter were assessed to determine the rate
      of performance of guideline measures. Approximately 1% of all results were
      manually reviewed in a validation process designed to determine the reliability
      of the electronic medical record based system. RESULTS: A total of 3,494 eligible
      encounters were evaluated in the final analysis. Provider adherence rates with
      the 9 measures recommended in the guidelines varied by measure from 53.0% to
      92.8%. The rate of performance of 5 not routinely recommended measures was 10.2%
      or less. Post-void residual and urinary flow measurement were optional measures,
      and were performed on 68.1% and 4.6% of new encounters respectively. Manual
      validation revealed the electronic medical record data extraction was concordant
      with manual review in 96.7% of cases (95% CI 94.8-98.5). CONCLUSIONS: Using
      electronic medical record based data extraction techniques, we reliably document
      a baseline adherence rate with AUA guidelines on the management of benign
      prostatic hyperplasia. Establishing this benchmark will be important for future
      investigation into patient outcomes related to guideline adherence and into
      methods for improving provider adherence.

PMID- 24931807
TI  - Genome-wide SNP analysis reveals a genetic basis for sea-age variation in a wild
      population of Atlantic salmon (Salmo salar).
AB  - Delaying sexual maturation can lead to larger body size and higher reproductive
      success, but carries an increased risk of death before reproducing. Classical
      life history theory predicts that trade-offs between reproductive success and
      survival should lead to the evolution of an optimal strategy in a given
      population. However, variation in mating strategies generally persists, and in
      general, there remains a poor understanding of genetic and physiological
      mechanisms underlying this variation. One extreme case of this is in the Atlantic
      salmon (Salmo salar), which can show variation in the age at which they return
      from their marine migration to spawn (i.e. their 'sea age'). This results in
      large size differences between strategies, with direct implications for
      individual fitness. Here, we used an Illumina Infinium SNP array to identify
      regions of the genome associated with variation in sea age in a large population
      of Atlantic salmon in Northern Europe, implementing individual-based genome-wide
      association studies (GWAS) and population-based FST outlier analyses. We
      identified several regions of the genome which vary in association with phenotype
      and/or selection between sea ages, with nearby genes having functions related to
      muscle development, metabolism, immune response and mate choice. In addition, we
      found that individuals of different sea ages belong to different, yet sympatric
      populations in this system, indicating that reproductive isolation may be driven
      by divergence between stable strategies. Overall, this study demonstrates how
      genome-wide methodologies can be integrated with samples collected from wild,
      structured populations to understand their ecology and evolution in a natural
      context. 

PMID- 24931808
TI  - Epidemiology of infective endocarditis in a tertiary-center in Jerusalem: a 3
      year prospective survey.
AB  - BACKGROUND: Epidemiological features of infective endocarditis have changed
      during the last decades because of increases in the prevalence of health care
      exposure and of Staphylococcus aureus bloodstream infection. Consequently, the
      role of surgery is evolving. We aim to provide a contemporary profile of
      epidemiological, microbiological, and clinical features of infective endocarditis
      in a tertiary medical center, and identify predictors of mortality. METHODS: A
      prospective observational cohort study of consecutive adult patients with
      definite endocarditis according to the modified Duke criteria. Data were
      collected from January 1, 2009 through October 31, 2011 following a predefined
      case report form designed by the ICE-PCS. RESULTS: Among 70 endocarditis
      episodes, 25.7% involved prosthetic valves and 11.5% were device related. Forty
      four percent of episodes were health-care associated. The predominant causative
      microorganism on native valve, prosthetic valve and device related endocarditis
      was Staphylococcus aureus (33.3%). Viridans group streptococci accounted for the
      majority of community-acquired endocarditis (36.1%). At least one complication
      occurred in 50% of the episodes. One third of the patients who had an indication
      for surgery were operated upon. Six month case fatality ratio was 40%. Sixty-five
      percent of patients with a contraindication to surgery died, compared with 9% and
      28.5% who were treated surgically and medically, respectively. In multivariable
      analysis, age was a predictor of mortality. CONCLUSION: Compared with other
      series, we observed more health-care associated endocarditis, and a higher
      mortality. Nearly half of all deaths were in patients who had a contraindication
      to surgery. Careful evaluation of contraindications to surgery is warranted.

PMID- 24931809
TI  - Peripheral blood cells inform on the presence of breast cancer: a population
      based case-control study.
AB  - Tumor-host interactions extend beyond the local microenvironment and cancer
      development largely depends on the ability of malignant cells to hijack and
      exploit the normal physiological processes of the host. Here, we established that
      many genes within peripheral blood cells show differential expression when an
      untreated breast cancer (BC) is present, and harnessed this fact to construct a
      50-gene signature that distinguish BC patients from population-based controls.
      Our results were derived from a series of large datasets within our unique
      population-based Norwegian Women and Cancer cohort that allowed us to investigate
      the influence of medications and tumor characteristics on our blood-based test,
      and were further tested in two external datasets. Our 50-gene signature contained
      cytostatic signals including the specific suppression of the immune response and
      medications influencing transcription involved in those processes were identified
      as confounders. Through analysis of the biological processes differentially
      expressed in blood, we were able to provide a rationale as to why the systemic
      response of the host may be a reliable marker of BC, characterized by the
      underexpression of both immune-specific pathways and "universal" cell programs
      driven by MYC (i.e., metabolism, growth and cell cycle). In conclusion, gene
      expression of peripheral blood cells is markedly perturbed by the specific
      presence of carcinoma in the breast and these changes simultaneously engage a
      number of systemic cytostatic signals emerging connections with immune escape of
      BC. 

PMID- 24931812
TI  - Neuromodulatory and anti-inflammatory ingredient for sensitive skin: in vitro
      assessment.
AB  - The manifestation of sensitive skin occurs as a consequence of increased
      permeability of the Stratum corneum, besides the involvement of neuro-immune
      endocrine system. In this study, we evaluated the effects of an active ingredient
      SensC on the production of neuropeptides substance P (SP), enkephalin and beta
      endorphin; eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4);
      histamine, transient receptor potential vanilloid subfamily member 1 (TRPV1), and
      envelope proteins filaggrin and involucrin, using an in vitro model of human cell
      culture. Our results demonstrated that treatment of keratinocyte cultures with
      SensC prevented the increase of all evaluated inflammatory mediators induced by
      interleukin-1 alpha (IL-1alpha). As the same way, SensC provides decrease in the
      synthesis of TRPV1. Regarding the synthesis of envelope proteins, SensC promoted
      increases for filaggrin and involucrin levels, when compared to control group.
      Considering the absence of appropriate treatment, the availability of
      ingredients, such as SensC, with antiinflammatory and protective barrier
      properties can be a significant tool for preventing neurosensorial symptoms
      associated with sensitive skin.

PMID- 24931814
TI  - Impaired ambulation and steroid therapy impact negatively on bone health in
      multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: The prevalence of osteopenia and osteoporosis is higher
      amongst patients with multiple sclerosis in comparison with the general
      population. In addition to the general determinants of bone health, two factors
      may contribute to reduced bone mineral density in multiple sclerosis: physical
      disability and corticosteroid therapy. The aim of this study was to examine the
      effect of physical disability and steroid exposure on bone health in weight
      bearing bones and spine and on the incidence of low-trauma fractures in multiple
      sclerosis. METHODS: In this retrospective analysis of prospectively collected
      data, associations between bone mineral density (at the femoral neck, total femur
      and the lumbar spine) and its change with disability or cumulative steroid dose
      were evaluated with random-effect models adjusted for demographic and clinical
      determinants of bone health. The incidence of low-trauma fractures during the
      study follow-up was evaluated with Andersen-Gill models. RESULTS: Overall, 474
      and 438 patients were included in cross-sectional and longitudinal analyses
      (follow-up 2347 patient-years), respectively. The effect of severely impaired
      gait was more apparent in weight-bearing bones (P <= 10(-15) ) than in spine (P =
      0.007). The effect of cumulative steroid dose was relatively less pronounced but
      diffuse (P <= 10(-4) ). Risk of low-trauma fractures was associated with
      disability (P = 0.02) but not with cumulative steroid exposure and was greater
      amongst patients with severely impaired gait (annual risk 3.5% vs. 3.0%).
      Synergistic effects were found only between cumulative steroid dose in patients
      ambulatory without support (P = 0.02). CONCLUSIONS: Bone health and the incidence
      of low-trauma fractures in multiple sclerosis are more related to impaired gait
      than to extended corticosteroid therapy.

PMID- 24931811
TI  - A meta-analysis of group cognitive behavioral therapy for insomnia.
AB  - Insomnia is the most common sleep disorder among the general population. Although
      cognitive behavioral therapy for insomnia (CBT-I) is the psychological treatment
      of choice, the availability of individual therapy is often not sufficient to meet
      the demand for treatment. Group treatment can increase the efficiency of
      delivery, but its efficacy has not been well-established. Randomized controlled
      trials (RCTs) comparing group CBT-I to a control group in patients with insomnia
      were identified. A review of 670 unique citations resulted in eight studies that
      met criteria for analysis. Outcome variables included both qualitative (e.g.,
      sleep quality) and quantitative (e.g., sleep diary) outcomes, as well as
      depression and pain severity, at both pre- to post-treatment and follow-up (3-12
      mo post-treatment). Overall, we found medium to large effect sizes for sleep
      onset latency, sleep efficiency, and wake after sleep onset and small effect
      sizes for pain outcomes. Effect sizes remained significant at follow-up,
      suggesting that treatment gains persist over time. Other variables, including
      total sleep time, sleep quality, and depression, showed significant improvements,
      but these findings were limited to the within treatment group analyses. It is
      clear that group CBT-I is an efficacious treatment. Implications for stepped care
      models for insomnia are discussed. 

PMID- 24931815
TI  - Prophylactic eculizumab for kidney transplantation in a child with atypical
      hemolytic uremic syndrome due to complement factor H mutation.
AB  - We present a case of successful deceased-donor kidney transplantation in a three
      yr-old child with aHUS due to complement factor H mutation, using only
      prophylactic eculizumab treatment prior to transplant. She developed disease
      exacerbation in the immediate post-operative period despite having therapeutic
      eculizumab concentrations and evidence for complete complement pathway blockade.
      The patient responded well to additional doses of eculizumab and has maintained
      excellent graft function and disease control in the first year post
      transplantation. The optimal dosing scheme for eculizumab in the perioperative
      period remains to be determined. More sensitive biomarkers of early disease
      activity are needed to improve disease monitoring. Finally, the duration of
      eculizumab therapy in patients with aHUS remains to be determined. 

PMID- 24931816
TI  - Protective effect of Flos puerariae extract following acute alcohol intoxication
      in mice.
AB  - BACKGROUND: The effect of Flos Puerariae extract (FPE) on alcohol metabolism,
      hepatic injury, and memory impairment was assessed following acute ethanol (EtOH)
      intoxication in mice. METHODS: The model of acute EtOH intoxication was
      established by intragastric administration with 8 g/kg EtOH in mice. FPE was
      orally administrated (gavage) once a day for 7 consecutive days. Mice were
      randomly divided into 4 groups: control group, model group, and FPE groups (100,
      200 mg/kg). Alcohol tolerance and intoxication time, blood alcohol concentration,
      the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)
      in liver, aspartate amino transferase (AST) and alanine amino transferase (ALT)
      in serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase
      and the formation of malondialdehyde (MDA) in both liver and brain, as well as
      memory ability were determined after acute alcohol exposure. RESULTS: Compared
      with model group, pretreatment with FPE significantly prolonged alcohol tolerance
      time and shortened intoxication time, which is accompanied by decreased blood
      alcohol concentration and elevated activities of ADH and ALDH in liver. Moreover,
      the index of hepatic injury, ALT, and AST activities in serum was markedly
      decreased by pretreatment with FPE. Additionally, decreased MDA level, enhanced
      GSH-px and catalase activities in liver, as well as enhanced SOD and catalase
      activities in brain were found in FPE pretreated mice after acute exposure to
      EtOH. Furthermore, FPE pretreated mice showed markedly relieved memory disruption
      following acute EtOH intoxication. CONCLUSIONS: This study suggests that FPE
      pretreatment could enhance alcohol metabolism, prevent hepatic injury, and
      relieve memory impairment after acute alcohol intoxication and that this effect
      is likely related to its modulation on the alcohol metabolizing and antioxidant
      enzymes.

PMID- 24931817
TI  - Animal models of disc degeneration based on transgenic and stress methods.

PMID- 24931818
TI  - Response to familial hypercholesterolemia: an under-recognized but significant
      concern in cardiology practice.

PMID- 24931819
TI  - Myxedema.

PMID- 24931821
TI  - The natural history of intravascular lymphomatosis.
AB  - Intravascular lymphomatosis (IVL) is a rare and clinically devastating form of
      extranodal B-cell non-Hodgkin's lymphoma. We performed a comprehensive analysis
      of the literature on IVL's published between 1959 and 2011 and evaluated the
      natural history as well as identified prognostic and predictive factors in
      patients. Nonparametric two-tailed Mann-Whitney U-test and Mantel-Cox log rank
      test were used to evaluate the survival intervals and prognostic factors.
      Multivariate analysis of variance (MANOVA) and chi-squared statistics were
      carried out to examine treatment-related predictive factors. Of the 740 patients
      with IVL, 651 (88%) had a diagnosis of B-cell lymphoma, 45 (6%) with T-cell
      lymphoma, and 12 patients (2%) with NK cell lymphoma. Central nervous system
      (CNS) IVL had the highest proportion of postmortem diagnosis, 250 (60%) compared
      to 21 (8%) of skin, 28 (11%) of bone marrow (BM) and spleen, and 17 (7%) of lung
      IVL's. Age <70 years (P = 0.0073), non-CNS site of initial diagnosis (P =
      0.0014), lactate dehydrogenase (LDH) <700 (P = 0.0112), and rituximab treatment
      (P < 0.0001) were favorable prognostic factors. Gender, ethnicity, hemoglobin, BM
      biopsy, and the type of imaging studies used were not significant. Rituximab and
      doxorubicin treatment worked significantly better in patients with age >71 and
      LDH >577 compared to nonrituximab, nondoxorubicin regimens (MANOVA 2 degrees of
      freedom, P = 0.0345), with a median time from treatment to death of 20.0 (95%
      confidence interval [CI] 14.0-N/A, n = 14) months versus 2.0 (95%CI 0.5-N/A, n =
      5) (chi(2) = 4.7, P = 0.0304). Patients with CNS IVL relapsed primarily in the
      CNS (88%) while same-organ relapse occurred less frequently in skin (23%), BM and
      spleen (50%) and lung (20%) IVL's. Our results indicate that IVL is primarily a
      disease of B-lymphoma cells. Timely diagnosis and treatment with rituximab-based
      chemotherapy improve patient survival. The pattern of recurrence is different
      between CNS IVL and IVL's in other organs.

PMID- 24931822
TI  - NMR structure of an ethylene interstrand cross-linked DNA which mimics the lesion
      formed by 1,3-bis(2-chloroethyl)-1-nitrosourea.
AB  - The bisalkylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), used in
      cancer chemotherapy to hinder cellular proliferation, forms lethal interstrand
      cross-links (ICLs) in DNA. BCNU generates an ethylene linkage connecting the two
      DNA strands at the N1 atom of 2'-deoxyguanosine and N3 atom of 2'-deoxycytidine,
      which is a synthetically challenging probe to prepare. To this end, an ICL duplex
      linking the N1 atom of 2'-deoxyinosine to the N3 atom of thymidine via an
      ethylene linker was devised as a mimic. We have solved the structure of this ICL
      duplex by a combination of molecular dynamics and high-field NMR experiments. The
      ethylene linker is well-accommodated in the duplex with minimal global and local
      perturbations relative to the unmodified duplex. These results may account for
      the substantial stabilization of the ICL duplex observed by UV thermal
      denaturation experiments and provides structural insights of a probe that may be
      useful for DNA repair studies.

PMID- 24931823
TI  - Intraoperative target-controlled infusion anesthesia application using
      remifentanil hydrochloride with etomidate in patients with severe burn as
      monitored using Narcotrend.
AB  - OBJECTIVE: This study aims to evaluate the feasibility of intraoperative
      composite target-controlled infusion (TCI) anesthesia application using
      remifentanil hydrochloride with etomidate in patients with severe burns, as
      monitored by Narcotrend. METHODS: A total of 40 patients with severe burns with
      eschar excisions and skin grafts were randomly and equally grouped into the
      etomidate (E) and the propofol groups (P). Anesthesia was induced and maintained
      by a remifentanil hydrochloride TCI combined with etomidate or propofol. The
      depth of anesthesia and other relevant indicators were recorded through
      intraoperative electroencephalogram monitoring using a Narcotrend monitor.
      RESULTS: No statistically significant differences were observed between the drug
      withdrawal times, eye opening requirements, or orientation recoveries of the two
      groups (P>0.05). The cortisol and aldosterone levels in group E were
      significantly lower than those in group P 24h post operation (P<0.05). No
      significant differences between the number of operations, hospitalization
      duration, mean arterial pressure, heart rate, and postoperative adverse reaction
      incidence of the two groups were observed at each time point (P>0.05).
      CONCLUSION: The application of a composite remifentanil hydrochloride combined
      with etomidate TCI is feasible for the early eschar excision in patients with
      severe burns.

PMID- 24931824
TI  - A new flap design for release of parallel contracture bands: dual opposing five
      flap z-plasty.
AB  - Skin contractures secondary to burn and other types of trauma can be encountered
      on almost every part of human body, best addressed by a custom treatment protocol
      tailored for each patient. Skin graft, local flap as well as distant flap options
      are available, each with intrinsic advantages and disadvantages. In the presence
      of weblike contracture the utilization of local tissue, when available, is a
      prefered approach for a relatively better appearance through a reasonably simpler
      surgical intervention, compared to skin graft applications and distant flap
      options. Among many other techniques and modalities utilized for this purpose,
      the dual opposing five-flap z-plasty method which is a novel method designed as a
      modification of the paired five-flap z-plasty technique promises to be a useful
      treatment option for the release of parallel contracture bands with satisfactory
      results in selected patients. 

PMID- 24931825
TI  - Identification of bacteriophage virion proteins by the ANOVA feature selection
      and analysis.
AB  - The bacteriophage virion proteins play extremely important roles in the fate of
      host bacterial cells. Accurate identification of bacteriophage virion proteins is
      very important for understanding their functions and clarifying the lysis
      mechanism of bacterial cells. In this study, a new sequence-based method was
      developed to identify phage virion proteins. In the new method, the protein
      sequences were initially formulated by the g-gap dipeptide compositions.
      Subsequently, the analysis of variance (ANOVA) with incremental feature selection
      (IFS) was used to search for the optimal feature set. It was observed that, in
      jackknife cross-validation, the optimal feature set including 160 optimized
      features can produce the maximum accuracy of 85.02%. By performing feature
      analysis, we found that the correlation between two amino acids with one gap was
      more important than other correlations for phage virion protein prediction and
      that some of the 1-gap dipeptides were important and mainly contributed to the
      virion protein prediction. This analysis will provide novel insights into the
      function of phage virion proteins. On the basis of the proposed method, an online
      web-server, PVPred, was established and can be freely accessed from the website
      (http://lin.uestc.edu.cn/server/PVPred). We believe that the PVPred will become a
      powerful tool to study phage virion proteins and to guide the related
      experimental validations.

PMID- 24931826
TI  - Expression of bone markers and micro-CT analysis of alveolar bone during
      orthodontic relapse.
AB  - OBJECTIVES: To investigate biological changes in alveolar bone occurring during
      orthodontic relapse. MATERIALS AND METHODS: Rat maxillary first molars were moved
      mesially for 10 days. After orthodontic tooth movement (OTM), appliances were
      removed, and the molars were allowed to relapse for one, three, five, seven, 14
      or 21 days. Changes in 3D morphometric parameters of bone located mesial to the
      first molars were evaluated by micro-CT. Total RNA was isolated from the same
      bone site, and real-time RT-PCR was used to measure the expression of bone
      formation and resorption markers. RESULTS: One day after appliance removal, the
      molars relapsed to a mean 73% of the achieved OTM and then steadily relapsed to
      93% at 21 days. Tissue mineral density and per cent bone volume increased over
      the experimental period. Inversely, there was a decrease in total porosity. Gene
      expression of OCN, Coll-I and ALP decreased during OTM, whilst as the molars
      relapsed showed tended to increase. Gene expression of RANKL and TRAP increased
      during OTM. Changes in mRNA expression of H(+)-ATPase were minor. By 21 days post
      appliance removal, the remodelling process in rats appeared to have returned to
      control levels. CONCLUSIONS: Bone tissue reactions on a molecular level are
      similar during OTM and orthodontic relapse. These findings validate the
      importance of immediate retention following active OTM.

PMID- 24931827
TI  - Application of response surface methodology to optimise microbial inactivation of
      shrimp and conch by supercritical carbon dioxide.
AB  - BACKGROUND: Supercritical carbon dioxide (SC-CO2 ) has been shown to have a good
      pasteurising effect on food. However, very few research papers have investigated
      the possibility to exploit this treatment for solid foods, particularly for
      seafood. Considering the microbial safety of raw seafood consumption, the study
      aimed to explore the feasibility of microbial inactivation of shrimp (Metapenaeus
      ensis) and conch (Rapana venosa) by SC-CO2 treatment. RESULTS: Response surface
      methodology (RSM) models were established to predict and analyse the SC-CO2
      process. A 3.69-log reduction in the total aerobic plate count (TPC) of shrimp
      was observed by SC-CO2 treatment at 53 degrees C, 15 MPa for 40 min, and the
      logarithmic reduction in TPC of conch was 3.31 at 55 degrees C, 14 MPa for 42
      min. Sensory scores of the products achieved approximately 8 (desirable). The
      optimal parameters for microbial inactivation of shrimp and conch by SC-CO2 might
      be 55 degrees C, 15 MPa and 40 min. CONCLUSION: SC-CO2 exerted a strong
      bactericidal effect on the TPC of shrimp and conch, and the products maintained
      good organoleptic properties. This study verified the feasibility of microbial
      inactivation of shrimp and conch by SC-CO2 treatment.

PMID- 24931828
TI  - Localization of the cerebellar cortical zone mediating acquisition of eyeblink
      conditioning in rats.
AB  - Delay eyeblink conditioning is established by paired presentations of a
      conditioned stimulus (CS) such as a tone or light and an unconditioned stimulus
      (US) that elicits eyelid closure before training. The CS and US inputs converge
      on Purkinje cells in the cerebellar cortex. The cerebellar cortex plays a
      substantial role in acquisition of delay eyeblink conditioning in rabbits and
      rodents, but the specific area of the cortex that is necessary for acquisition in
      rodents has not been identified. A recent study identified an eyeblink microzone
      in the mouse cerebellar cortex at the base of the primary fissure (Heiney, Kim,
      Augustine, & Medina, 2014). There is no evidence that the cortex in this eyeblink
      microzone plays a role in rodent eyeblink conditioning but it is a good candidate
      region. Experiment 1 examined the effects of unilateral (ipsilateral to the US)
      lesions of lobule HVI, the lateral anterior lobe, or the base of the primary
      fissure on eyeblink conditioning in rats. Lesions of either the anterior lobe or
      lobule HVI impaired acquisition, but lesions of the base of the primary fissure
      produced the largest deficit. Experiment 2 used reversible inactivation with
      muscimol to demonstrate that inactivation of the putative eyeblink microzone
      severely impaired acquisition and had only a modest effect on retention of
      eyeblink conditioning. The findings indicate that the base of the primary fissure
      is the critical zone of the cerebellar cortex for acquisition of eyeblink
      conditioning in rats. 

PMID- 24931829
TI  - Keratin pearl degradation in oral squamous cell carcinoma: reciprocal roles of
      neutrophils and macrophages.
AB  - BACKGROUND: We have reported that neutrophilic infiltration was associated with
      round-shaped dyskeratosis foci, a kind of keratin pearl, of oral carcinoma in
      situ and that those inflammatory cells are recruited from intra-epithelially
      entrapped blood vessels. Based on these lines of evidence, we have formulated a
      hypothesis that keratin pearls are terminally degraded by neutrophils. To confirm
      this hypothesis, we investigated immunohistochemically stepwise degradation of
      keratin pearls in oral squamous cell carcinoma (SCC) to clarify any other type
      scavenger cells in addition to neutrophils are involved in this particular
      degradation process. METHODS: Neutrophils (neutrophil elastase) and macrophage
      subpopulations (CD68, CD163 and CD204) were immunohistochemically localized in 30
      cases of oral SCC with typical round-shaped keratin pearls. SCC cells were
      revealed by immunohistochemistry for keratin (K) 17, and blood vessels were
      demonstrated by CD31. RESULTS: Keratin pearl degradation process was divided into
      four steps: (i) intact stage: no macrophage infiltration but minimal neutrophils
      were found in keratin pearls; (ii) neutrophil recruit stage: no macrophage
      infiltration but focal neutrophilic infiltration within the pearls; (iii)
      neutrophil predominant stage: dense neutrophil infiltration with minimal
      macrophages and segregated keratinized cancer cells strongly positive for K17;
      and (iv) macrophage predominant stage: dense infiltration of CD68-, CD163
      (mononuclear)- and CD204 (multinucleated)-positive macrophages engulfing detached
      keratinized SCC cells. CONCLUSION: Keratin pearl degradation in oral SCC is
      strictly regulated by two types of scavenger cells: neutrophils, which perform
      initial tasks, and macrophages, which reciprocally take over from neutrophils the
      role to finalize the degradation processes.

PMID- 24931831
TI  - Principles and engineering of antibody folding and assembly.
AB  - Antibodies are uniquely suited to serve essential roles in the human immune
      defense as they combine several specific functions in one hetero-oligomeric
      protein. Their constant regions activate effector functions and their variable
      domains provide a stable framework that allows incorporation of highly diverse
      loop sequences. The combination of non-germline DNA recombination and mutation
      together with heavy and light chain assembly allows developing variable regions
      that specifically recognize essentially any antigen they may encounter. However,
      this diversity also requires tailor-made mechanisms to guarantee that folding and
      association of antibodies is carefully this diversity also requires tailor-made
      mechanisms to guarantee that folding and association of antibodies is carefully
      controlled before the protein is secreted from a plasma cell. Accordingly, the
      generic immunoglobulin fold beta-barrel structure of antibody domains has been
      fine-tuned during evolution to fit the different requirements. Work over the past
      decades has identified important aspects of the folding and assembly of antibody
      domains and chains revealing domain specific variations of a general scheme. The
      most striking is the folding of an intrinsically disordered antibody domain in
      the context of its partner domain as the basis for antibody assembly and its
      control on the molecular level in the cell. These insights have not only allowed
      a better understanding of the antibody folding process but also provide a wealth
      of opportunities for rational optimization of antibody molecules. In this review,
      we summarize current concepts of antibody folding and assembly and discuss how
      they can be utilized to engineer antibodies with improved performance for
      different applications. This article is part of a Special Issue entitled: Recent
      advances in the molecular engineering of antibodies.

PMID- 24931830
TI  - Prospective multicentre observational study of lymphedema therapy: POLIT study.
AB  - OBJECTIVE: Lymphedema treatment is based on Decongestive Lymphedema Therapy (DLT)
      with an intensive phase followed by a long-term maintenance phase. This study
      aimed to observe volume variation over the intensive phase and 6 months later.
      METHODS: Prospective multicentre observational study of patients with unilateral
      lymphedema. The primary objective was to assess lymphedema volume variation
      between baseline, the end of intensive phase and 6 months later. Secondary
      objectives were to assess the frequency of heaviness limiting limb function and
      treatments safety predictors for volume reduction. RESULTS: Three hundred and six
      patients (89.9% women; 59.9+/-14.3 years old) with upper/lower (n=184/122) limb
      lymphedema were included. At the end of the intensive phase, median excess
      lymphedema volume reduction was 31.0% (41.7-19.9) followed by a 16.5% (5.9-42.3)
      median increase over the 6-month maintenance period phase. Previous intensive
      treatment was the only significant predictor of this response. As compared to
      baseline, heaviness limiting limb use was much less frequently reported at the
      end of the reductive phase (75.5% versus 42.3% respectively), and was more
      frequent at the end of the maintenance phase (62.6%). The most frequent adverse
      events reported were skin redness and compression marks (18.4 and 15.7% of
      patients, respectively). Blisters requiring treatment stoppage were rare (1.4%).
      CONCLUSIONS: Intensive phase decreases lymphedema volume and heaviness limiting
      limb function. The benefit is partially abolished after the first 6 months of
      maintenance. There is a need to consider how to provide optimal patient care for
      the long-term control of lymphedema.

PMID- 24931832
TI  - From fluorescence polarization to Quenchbody: Recent progress in fluorescent
      reagentless biosensors based on antibody and other binding proteins.
AB  - Recently, antibody-based fluorescent biosensors are receiving considerable
      attention as a suitable biomolecule for diagnostics, namely, homogeneous
      immunoassay and also as an imaging probe. To date, several strategies for
      "reagentless biosensors" based on antibodies and natural and engineered binding
      proteins have been described. In this review, several approaches are introduced
      including a recently described fluorescent antibody-based biosensor Quenchbody,
      which works on the principle of fluorescence quenching of attached dye and its
      antigen-dependent release. The merits and possible demerits of each approach are
      discussed. This article is part of a Special Issue entitled: Recent advances in
      molecular engineering of antibody.

PMID- 24931833
TI  - Charge-transfer complexation between naphthalene diimides and aromatic solvents.
AB  - Naphthalene diimides (NDIs) form emissive ground-state charge-transfer (CT)
      complexes with various electron rich aromatic solvents like benzene, o-xylene and
      mesitylene. TD-DFT calculation of the complexes suggests CT interaction and
      accounts for the observed ground-state changes. 

PMID- 24931834
TI  - Light control of stoichiometry and motion in pseudorotaxanes comprising a
      cucurbit[7]uril wheel and an azobenzene-bipyridinium axle.
AB  - Pseudorotaxanes are the simplest prototypes for the construction of molecular
      machines based on threaded species. Investigation on molecular motions in these
      model systems is a necessary action for an efficient design of working molecular
      machines and motors. Herein we report on photoactive pseudorotaxanes based on the
      interaction between bipyridinium and cucurbit[7]uril (CB7). The molecular axle is
      composed of a central bipyridinium unit and two azobenzene moieties at the
      extremities. CB7 can form two different complexes with this molecule: a
      [2]pseudorotaxane, in which the macrocycle shuttles fast along the length of the
      axle, and a [3]pseudorotaxane, in which two CB7 s are confined at the extremities
      of the axle. Upon trans to cis isomerization of the azobenzene moieties, the
      [3]pseudorotaxane is destabilized, and only one CB7 resides on the axle,
      surrounding the bipyridinium unit. The system was successfully inserted into the
      core of liposomes, and preliminary investigations confirmed that it maintains its
      switching ability. 

PMID- 24931835
TI  - Mothers with intellectual disability, their experiences of maltreatment, and
      their children's attachment representations: a small-group matched comparison
      study.
AB  - Maternal intellectual disability (ID) is regarded a risk factor in child
      development, but there is no scientific evidence on maternal ID in relation to
      children's attachment. Using a matched comparison design, a small group (n = 23)
      of mothers diagnosed with ID was studied to help fill this gap. Besides maternal
      ID, we examined the role of abuse/trauma/maltreatment (ATM) in the mothers'
      biographies, along with potential confounds. Comparison group mothers (n = 25)
      had normal variations in intelligence and matched mothers with ID on residential
      area, income, child age, and sex. History of maternal ATM was assessed using a
      semi-structured interview and was found to be significantly more likely in the ID
      group mothers' experience than the comparison group mothers. Children's (M age =
      77 months) attachment representations were assessed with the Separation Anxiety
      Test. Among children of mothers with ID, a substantial minority (35%) had a
      secure and the vast majority (>80%) an organized attachment representation.
      Mothers with ID who had suffered elevated ATM were significantly more likely to
      have children who were scored high on disorganization and insecurity. We discuss
      possible implications of our findings for societal considerations regarding
      parenting and child attachment in the context of parental ID status.

PMID- 24931837
TI  - Granulomatous isotopic response possibly to herpes zoster in childhood.

PMID- 24931836
TI  - C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and
      frontotemporal dementia: a genome-wide meta-analysis.
AB  - OBJECTIVE: Substantial clinical, pathological, and genetic overlap exists between
      amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43
      inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a
      repeat expansion in C9orf72 was identified as the causal variant in a proportion
      of ALS and FTD cases. We sought to identify additional evidence for a common
      genetic basis for the spectrum of ALS-FTD. METHODS: We used published genome-wide
      association studies data for 4,377 ALS patients and 13,017 controls, and 435
      pathology-proven FTD-TDP cases and 1,414 controls for genotype imputation. Data
      were analyzed in a joint meta-analysis, by replicating topmost associated hits of
      one disease in the other, and by using a conservative rank products analysis,
      allocating equal weight to ALS and FTD-TDP sample sizes. RESULTS: Meta-analysis
      identified 19 genome-wide significant single nucleotide polymorphisms (SNPs) in
      C9orf72 on chromosome 9p21.2 (lowest p = 2.6 * 10(-12) ) and 1 SNP in UNC13A on
      chromosome 19p13.11 (p = 1.0 * 10(-11) ) as shared susceptibility loci for ALS
      and FTD-TDP. Conditioning on the 9p21.2 genotype increased statistical
      significance at UNC13A. A third signal, on chromosome 8q24.13 at the SPG8 locus
      coding for strumpellin (p = 3.91 * 10(-7) ) was replicated in an independent
      cohort of 4,056 ALS patients and 3,958 controls (p = 0.026; combined analysis p =
      1.01 * 10(-7) ). INTERPRETATION: We identified common genetic variants in
      C9orf72, but in addition in UNC13A that are shared between ALS and FTD. UNC13A
      provides a novel link between ALS and FTD-TDP, and identifies changes in
      neurotransmitter release and synaptic function as a converging mechanism in the
      pathogenesis of ALS and FTD-TDP.

PMID- 24931838
TI  - The abandoned controversy surrounding universal white blood cell reduction.

PMID- 24931839
TI  - Implementing Patient Blood Management in major orthopaedic procedures: orthodoxy
      or pragmatism?

PMID- 24931840
TI  - Evaluation of platelet cross-matching in the management of patients refractory to
      platelet transfusions.
AB  - BACKGROUND: Cross-match-compatible platelets are used to support thrombocytopenic
      patients who are refractory to randomly selected platelets. However, few studies
      have addressed the efficacy of using this strategy for patients requiring
      intensive platelet transfusion therapy. The aim of this study was to determine
      the effectiveness of cross-match-compatible platelets in an unselected group of
      patients refractory to platelets from random donors. MATERIALS AND METHODS: A
      total of 406 cross-match-compatible platelet components were administered to 40
      evaluable patients who were refractory to random-donor platelets. A solid-phase
      red cell adherence method was used for platelet cross-matching. The corrected
      count increment was used to monitor the effectiveness of each platelet
      transfusion. Multivariate analysis was performed to detect whether any variables
      could predict the response to transfusion. RESULTS: Statistically significant
      improvements were found in the mean corrected count increment when comparing
      cross-match-compatible platelets with randomly selected and incompatible
      platelets (p<0.001 for each). Compatible platelet transfusions were associated
      with a good response in 72.9% of cases while incompatible platelets were
      associated with a poor response in 66.7% of transfusion events (p<0.001). In the
      presence of clinical factors or alloimmunisation, compatible platelets were
      associated with good responses in 67.9% and 28.0% respectively vs 100% and 93.3%
      in their absence (p=0.009, p<0.001). Multivariate analysis revealed that cross
      matching and alloimmunisation were the strongest predictors of transfusion
      response at 1 hour, while ABO compatibility, type of units received, followed by
      alloimmunisation then clinical factors were predictors at 24 hours. DISCUSSION:
      Platelet cross-matching using the solid-phase red cell adherence technique is an
      effective and rapid first-line approach for the management of patients refractory
      to platelet transfusions.

PMID- 24931841
TI  - Patient blood management in orthopaedic surgery: a four-year follow-up of
      transfusion requirements and blood loss from 2008 to 2011 at the Balgrist
      University Hospital in Zurich, Switzerland.
AB  - BACKGROUND: The aim of this study was to investigate the impact of the
      introduction of a Patient Blood Management (PBM) programme in elective
      orthopaedic surgery on immediate pre-operative anaemia, red blood cell (RBC) mass
      loss, and transfusion. MATERIALS AND METHODS: Orthopaedic operations (hip,
      n=3,062; knee, n=2,953; and spine, n=2,856) performed between 2008 and 2011 were
      analysed. Period 1 (2008), was before the introduction of the PBM programme and
      period 2 (2009 to 2011) the time after its introduction. Immediate pre-operative
      anaemia, RBC mass loss, and transfusion rates in the two periods were compared.
      RESULTS: In hip surgery, the percentage of patients with immediate pre-operative
      anaemia decreased from 17.6% to 12.9% (p<0.001) and RBC mass loss was unchanged,
      being 626+/-434 vs 635+/-450 mL (p=0.974). Transfusion rate was significantly
      reduced from 21.8% to 15.7% (p<0.001). The number of RBC units transfused
      remained unchanged (p=0.761). In knee surgery the prevalence of immediate pre
      operative anaemia decreased from 15.5% to 7.8% (p<0.001) and RBC mass loss
      reduced from 573+/-355 to 476+/-365 mL (p<0.001). The transfusion rate dropped
      from 19.3% to 4.9% (p<0.001). RBC transfusions decreased from 0.53+/-1.27 to
      0.16+/-0.90 units (p<0.001). In spine surgery the prevalence of immediate pre
      operative anaemia remained unchanged (p=0.113), RBC mass loss dropped from 551+/
      421 to 404+/-337 mL (p<0.001), the transfusion rate was reduced from 18.6 to 8.6%
      (p<0.001) and RBC transfusions decreased from 0.66+/-1.80 to 0.22+/-0.89 units
      (p=0.008). DISCUSSION: Detection and treatment of pre-operative anaemia,
      meticulous surgical technique, optimal surgical blood-saving techniques, and
      standardised transfusion triggers in the context of PBM programme resulted in a
      lower incidence of immediate pre-operative anaemia, reduction in RBC mass loss,
      and a lower transfusion rate.

PMID- 24931842
TI  - Factor VIII and fibrinogen recovery in plasma after Theraflex methylene blue
      treatment: effect of plasma source and treatment time.
AB  - BACKGROUND: The quality of fresh-frozen plasma is affected by different factors.
      Factor VIII is sensitive to blood component storage processes and storage as well
      as pathogen-reduction technologies. The level of fibrinogen in plasma is not
      affected by the collection processes but it is affected by preparation and
      pathogen-reduction technologies. MATERIALS AND METHODS: The quality of plasma
      from whole blood and apheresis donations harvested at different times and treated
      with a pathogen-reduction technique, methylene blue/light, was investigated,
      considering, in particular, fibrinogen and factor VIII levels and recovery.
      RESULTS: The mean factor VIII level after methylene blue treatment exceeded 0.5
      IU/mL in all series. Factor VIII recovery varied between 78% and 89% in different
      series. The recovery of factor VIII was dependent on plasma source as opposed to
      treatment time. The interaction between the two factors was statistically
      significant. Mean levels of fibrinogen after methylene blue/light treatment
      exceeded 200 mg/dL in all arms. The level of fibrinogen after treatment
      correlated strongly with the level before treatment. There was a negative
      correlation between fibrinogen level before treatment and recovery. Pearson's
      correlation coefficient between factor VIII recovery and fibrinogen recovery was
      0.58. DISCUSSION: These results show a difference in recovery of factor VIII and
      fibrinogen correlated with plasma source. The recovery of both factor VIII and
      fibrinogen was higher in whole blood plasma than in apheresis plasma. Factor VIII
      and fibrinogen recovery did not appear to be correlated.

PMID- 24931843
TI  - Cost-effectiveness of leucoreduction for prevention of febrile non-haemolytic
      transfusion reactions.
AB  - BACKGROUND: The cost-effectiveness of universal leucoreduction of blood
      components remains unclear. When using leucoreduced red blood cells, the decrease
      in the rate of febrile non-haemolytic transfusion reactions (FNHTR) is the only
      proven, meaningful clinical benefit, whose relationship to costs can be
      calculated relatively easily. The aim of this study was to evaluate the cost
      effectiveness of leucoreduction in avoiding FNHTR. MATERIALS AND METHODS: Data
      were obtained from two large tertiary hospitals in Athens, Greece, over a 4-year
      period (2009-2012). The incidence of FNHTR in patients transfused with
      leucoreduced or non-leucodepleted red blood cells, the additional cost of
      leucoreduction and the cost to treat the FNHTR were estimated. The incremental
      cost-effectiveness ratio (ICER), which is the ratio of the change in costs to the
      incremental benefits of leucoreduction, was calculated. RESULTS: In total, 86,032
      red blood cell units were transfused. Of these, 53,409 were leucodepleted and
      32,623 were non-leucoreduced. Among patients transfused with leucodepleted units,
      25 cases (0.047%) met the criteria for having a FNHTR, while in patients treated
      with non-leucoreduced components, 134 FNHTR were observed (0.411%). The ICER of
      leucoreduction was ? 6,916 (i.e., the cost to prevent one case of FNHTR).
      CONCLUSIONS: Leucoreduction does not have a favourable cost-effectiveness ratio
      in relation to the occurrence of FNHTR. However, many factors, which could not be
      easily and accurately assessed, influence the long-term costs of transfusion. It
      is imperative to undertake a series of large, meticulously designed clinical
      studies across the entire spectrum of blood transfusion settings, to investigate
      most of the parameters involved.

PMID- 24931844
TI  - Clinical and serological responses following plasmapheresis in bullous
      pemphigoid: two case reports and a review of the literature.

PMID- 24931845
TI  - Hairy cell leukaemia and venous thromboembolism: a case report and review of the
      literature.

PMID- 24931846
TI  - Oxidative refolding of rPA in l-ArgHCl and in ionic liquids: A correlation
      between hydrophobicity, salt effects, and refolding yield.
AB  - The ionic liquid 1-ethyl-3-methyl imidazolium chloride (EMIM Cl) and the amino
      acid l-arginine hydrochloride (l-ArgHCl) have been successfully used to improve
      the yield of oxidative refolding for various proteins. However, the molecular
      mechanisms behind the actions of such solvent additives-especially of ionic
      liquids-are still not well understood. To analyze these mechanisms, we have
      determined the transfer free energies from water into ionic liquid solutions of
      proteinogenic amino acids and of diketopiperazine as peptide bond analogue. For
      EMIM Cl and 1-ethyl-3-methyl imidazolium diethyl phosphate, which had a
      suppressive effect on protein refolding, as well as for l-ArgHCl favorable
      interactions with amino acid side chains, but no favorable interactions with the
      peptide backbone could be observed. A quantitative analysis of other ionic
      liquids together with their already published effects on protein refolding showed
      that only solvent additives within a certain range of hydrophobicity,
      chaotropicity and kosmotropicity were effective for the refolding of recombinant
      plasminogen activator.

PMID- 24931847
TI  - Management of human papillomavirus-related unknown primaries of the head and neck
      with a transoral surgical approach.
AB  - BACKGROUND: Amidst a rising incidence of p16-positive (p16+) oropharyngeal
      cancer, a significant number of cases present as regionally metastatic disease
      with an "unknown" primary. Preliminary data support transoral surgery as an
      effective method of primary detection/treatment. METHODS: An observational cohort
      study of 65 p16+ unknown primary patients treated with transoral surgery and neck
      dissection (2001-2012) was performed. Adjuvant therapy and recurrence data were
      collected. Kaplan-Meier estimates were computed for disease-specific survival
      (DSS) and overall survival (OS). RESULTS: The primary detection rate was 89% (58
      of 65). Five-year DSS and OS were 98% and 97% for the detected group and 100% for
      the undetected, respectively. Seventeen patients were treated with surgery alone.
      Of the 47 patients receiving adjuvant therapy, radiation to the pharynx was
      spared in 36. CONCLUSION: The transoral approach was highly effective for the
      diagnosis and treatment of the p16+ unknown primary and laid the foundation for
      deescalated radiation by elimination of the pharyngeal field.

PMID- 24931848
TI  - Validation of the depression item bank from the Patient-Reported Outcomes
      Measurement Information System (PROMIS) in a three-month observational study.
AB  - The Patient-Reported Outcomes Measurement Information System (PROMIS) is an NIH
      Roadmap initiative devoted to developing better measurement tools for assessing
      constructs relevant to the clinical investigation and treatment of all diseases
      constructs such as pain, fatigue, emotional distress, sleep, physical
      functioning, and social participation. Following creation of item banks for these
      constructs, our priority has been to validate them, most often in short-term
      observational studies. We report here on a three-month prospective observational
      study with depressed outpatients in the early stages of a new treatment episode
      (with assessments at intake, one-month follow-up, and three-month follow-up). The
      protocol was designed to compare the psychometric properties of the PROMIS
      depression item bank (administered as a computerized adaptive test, CAT) with two
      legacy self-report instruments: the Center for Epidemiological Studies Depression
      scale (CESD; Radloff, 1977) and the Patient Health Questionnaire (PHQ-9; Spitzer
      et al., 1999). PROMIS depression demonstrated strong convergent validity with the
      CESD and the PHQ-9 (with correlations in a range from .72 to .84 across all time
      points), as well as responsiveness to change when characterizing symptom severity
      in a clinical outpatient sample. Identification of patients as "recovered" varied
      across the measures, with the PHQ-9 being the most conservative. The use of
      calibrations based on models from item response theory (IRT) provides advantages
      for PROMIS depression both psychometrically (creating the possibility of adaptive
      testing, providing a broader effective range of measurement, and generating
      greater precision) and practically (these psychometric advantages can be achieved
      with fewer items-a median of 4 items administered by CAT-resulting in less
      patient burden).

PMID- 24931849
TI  - Giving voice to study volunteers: comparing views of mentally ill, physically
      ill, and healthy protocol participants on ethical aspects of clinical research.
AB  - MOTIVATION: Ethical controversy surrounds clinical research involving seriously
      ill participants. While many stakeholders have opinions, the extent to which
      protocol volunteers themselves see human research as ethically acceptable has not
      been documented. To address this gap of knowledge, authors sought to assess views
      of healthy and ill clinical research volunteers regarding the ethical
      acceptability of human studies involving individuals who are ill or are
      potentially vulnerable. METHODS: Surveys and semi-structured interviews were used
      to query clinical research protocol participants and a comparison group of
      healthy individuals. A total of 179 respondents participated in this study: 150
      in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical
      research protocol participants) and 29 healthy individuals not enrolled in
      protocols. Main outcome measures included responses regarding ethical
      acceptability of clinical research when it presents significant burdens and
      risks, involves people with serious mental and physical illness, or enrolls
      people with other potential vulnerabilities in the research situation. RESULTS:
      Respondents expressed decreasing levels of acceptance of participation in
      research that posed burdens of increasing severity. Participation in protocols
      with possibly life-threatening consequences was perceived as least acceptable
      (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer,
      schizophrenia, depression, and post-traumatic stress disorder, was seen as
      ethically acceptable across respondent groups (range of means = [4.0, 4.7]).
      Mentally ill volunteers expressed levels of ethical acceptability for physical
      illness research and mental illness research as acceptable and similar, while
      physically ill volunteers expressed greater ethical acceptability for physical
      illness research than for mental illness research. Mentally ill, physically ill,
      and healthy participants expressed neutral to favorable perspectives regarding
      the ethical acceptability of clinical research participation by potentially
      vulnerable subpopulations (difference in acceptability perceived by mentally ill 
      healthy = -0.04, CI [-0.46, 0.39]; physically ill - healthy = -0.13, CI [-0.62, 
      .36]). CONCLUSIONS: Clinical research volunteers and healthy clinical research
      "naive" individuals view studies involving ill people as ethically acceptable,
      and their responses reflect concern regarding research that poses considerable
      burdens and risks and research involving vulnerable subpopulations. Physically
      ill research volunteers may be more willing to see burdensome and risky research
      as acceptable. Mentally ill research volunteers and healthy individuals expressed
      similar perspectives in this study, helping to dispel a misconception that those
      with mental illness should be presumed to hold disparate views.

PMID- 24931850
TI  - Mice with ablated adult brain neurogenesis are not impaired in antidepressant
      response to chronic fluoxetine.
AB  - The neurogenesis hypothesis of major depression has two main facets. One states
      that the illness results from decreased neurogenesis while the other claims that
      the very functioning of antidepressants depends on increased neurogenesis. In
      order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice),
      known to have virtually no adult brain neurogenesis, and we demonstrate that
      these mice successfully respond to chronic fluoxetine. After unpredictable
      chronic mild stress, mutant mice showed depression-like behavior in forced swim
      test, which was eliminated with chronic fluoxetine treatment, despite its lack of
      impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that
      new neurons are not indispensable for the action of antidepressants such as
      fluoxetine. Using forced swim test and tail suspension test, we also did not
      observe depression-like behavior in control cD2 KO mice, which argues against the
      link between decreased adult brain neurogenesis and major depression. 

PMID- 24931851
TI  - Molecular structures and metabolic characteristics of protein in brown and yellow
      flaxseed with altered nutrient traits.
AB  - The objectives of this study were to investigate the chemical profiles; crude
      protein (CP) subfractions; ruminal CP degradation characteristics and intestinal
      digestibility of rumen undegraded protein (RUP); and protein molecular structures
      using molecular spectroscopy of newly developed yellow-seeded flax (Linum
      usitatissimum L.). Seeds from two yellow flaxseed breeding lines and two brown
      flaxseed varieties were evaluated. The yellow-seeded lines had higher (P < 0.001)
      contents of oil (44.54 vs 41.42% dry matter (DM)) and CP (24.94 vs 20.91% DM)
      compared to those of the brown-seeded varieties. The CP in yellow seeds contained
      lower (P < 0.01) contents of true protein subfraction (81.31 vs 92.71% CP) and
      more (P < 0.001) extensively degraded (70.8 vs 64.9% CP) in rumen resulting in
      lower (P < 0.001) content of RUP (29.2 vs 35.1% CP) than that in the brown-seeded
      varieties. However, the total supply of digestible RUP was not significantly
      different between the two seed types. Regression equations based on protein
      molecular structural features gave relatively good estimation for the contents of
      CP (R(2) = 0.87), soluble CP (R(2) = 0.92), RUP (R(2) = 0.97), and intestinal
      digestibility of RUP (R(2) = 0.71). In conclusion, molecular spectroscopy can be
      used to rapidly characterize feed protein molecular structures and predict their
      nutritive value. 

PMID- 24931852
TI  - Applicability of the Demirjian method for dental assessment of southern Turkish
      children.
AB  - Age-related legal problems are especially common in underdeveloped parts of
      Turkey. In terms of civil and criminal law, the ages from 13 years to 18 years
      are critical in our country. Estimation of age is a very significant in aspect of
      accordance with laws. The aims of this study were to evaluate the applicability
      and accuracy of the Demirjian technique for assessing southern Turkish children;
      to analyze the sexual dimorphism of dental age in the studied groups; and to
      define the relationship between the dental age and the degree of mineralization
      in mandibular permanent tooth in southern Turkish children. This study was
      performed using panoramic radiographs from 932 healthy southern Turkish children,
      444 girls and 488 boys aged between 4 and 18 years. Statistical evaluations were
      performed using SPSS (Statistical Package for Social Sciences) for Windows 13.0
      software. The mean difference between dental and chronological age was calculated
      for each age and sex group. The paired t-test was used to compare all data. The
      chi-square test was used for between-group comparisons of categorical variables.
      Continuous variables were tested for normality using the Kolmogorov-Smirnov test.
      Relationships between continuous variables were examined using Pearson's
      correlation coefficient. The same observer re-examined 700 teeth three months
      after the first examination. The results were evaluated with the intraclass
      correlation test and both measurements were statistically significantly similar
      with each other(R = 0.982, p = 0.0001). .Dental age (DA) and chronological age
      (CA) were consistent for boys in the 16-16.9 age group and for girls in the 9-9.9
      and 15-15.9 age groups. From this study, we can conclude that dental age varies
      across ethnic populations. Additionally, dental maturation varies across
      different regions of the same country. Because Demirjian's standards are not
      suitable for all age groups of southern Turkish children, a new table is
      necessary for evaluating this population. Future studies using multi-ethnic
      population data are needed to establish the international applicability of
      Demirjian's method.

PMID- 24931853
TI  - Lip print identification: People v. Davis or the convenient citation.

PMID- 24931854
TI  - Sudden cardiac death from parvovirus B19 myocarditis in a young man with Brugada
      syndrome.
AB  - Cardiovascular diseases are the leading cause of sudden death all over the world.
      The aetiology of sudden cardiac death among young adults includes Brugada
      syndrome and myocarditis. Brugada syndrome is a genetic abnormality of sodium
      channels in the myocardium with a characteristic electrocardiographic pattern.
      Myocarditis has several aetiologies including infections. One of the most common
      cardiotropic viruses is parvovirus B19. This infection presents as a febrile
      illness in childhood and may result in fatal outcome, more frequently in adults.
      In this report we present a case of a young man who suffered from a mild upper
      respiratory tract infection. After recovery he had an episode of syncope and was
      diagnosed with Brugada syndrome. Some weeks later he died suddenly at home while
      sleeping. The detailed forensic pathological, histological and microbiological
      investigation revealed a parvovirus B19-associated myocarditis. Synergic effect
      of structural and functional abnormalities of the myocardium may lead to death.
      The cause and potential complications (eg. myocarditis) of even mild infections
      should be monitored carefully. 

PMID- 24931855
TI  - Neck injury patterns resulting from the use of petrol and electric chainsaws in
      suicides. Report on two cases.
AB  - Suicides due to neck injuries caused by chainsaws are uncommon events. The
      cutting elements of petrol and electric chainsaws produce different features in
      lethal neck injuries. The accurate evaluation of the death scene, of the power
      and mechanical characteristics of the chainsaw and of wound morphology are all
      essential in distinguishing a case of suicide. 

PMID- 24931856
TI  - The case for a cost-effective central coronial database following an analysis of
      coronial records relating to deaths in nursing homes.
AB  - In order to demonstrate the potential wider epidemiological application of the
      data held in coroners' files, this paper uses an analysis of nursing home deaths
      reported to the coroner in County Kildare, Ireland. We examine the deaths in
      relation to ages, primary causes of death and rates of post-mortem examination.
      Knowing that Europe's population is increasing in age, the analyses presented
      here show the type of information that could be made available relating to
      certain population cohorts. Currently, there is no easily accessible way to
      obtain this information in Ireland, so we present the case for the implementation
      of a central coroner's database with potential for application in other
      jurisdictions but with the caveat that it must be cost-effective and use current
      resources, rather than establishing new ones. 

PMID- 24931857
TI  - Pattern of acute poisonings in children below 15 years--a study from Mangalore,
      South India.
AB  - Acute poisoning in children is a problem ubiquitous in distribution and is an
      important paediatric emergency. The present research was aimed to study the
      pattern and outcome of childhood poisoning under the age of 15 years at a
      tertiary care centre in South India to characterize the problem of acute
      paediatric poisoning among the children in different age group in the region.
      Medical records of all poisoning patients admitted during 2010 and 2011 were
      reviewed, and the information relating to the sociodemographic and clinical
      profile of the patients was recorded. Acute poisoning was reported in 81 children
      aged below 15 years during the study period. 50.6% were boys (n = 41) and 49.4%
      girls (n = 40). The mean age of the study sample was 6.8 years. Mean age was
      observed to be higher in females than males. The maximum number of cases were
      observed in the below 5 years age group (n = 45). A male predominance was evident
      in the below 5 years age group, while a female predominance in the age group
      between 10 and 15 years. Kerosene (n = 23, 28.4%) and organophosphate compounds
      (n = 16, 19.8%) were the most common agents responsible for poisoning in
      children. The majority of the poisoning cases were reported to the hospital
      within 12 h of the incident (n = 65, 83.3%). The mortality in paediatric
      poisoning was observed to be 7.4%. The majority of the children (n = 68, 84.0%)
      recovered, while seven patients had left the hospital against medical advice
      (8.6%). The study reports agrochemicals and hydrocarbons to be the most commonly
      implicated agents in paediatric poisoning. The cause of paediatric poisonings
      varies in different age groups and hence, preventive strategies should be planned
      accordingly.

PMID- 24931858
TI  - The investigation of deaths in custody: a qualitative analysis of problems and
      prospects.
AB  - The right to be treated humanely when detained is universally recognized.
      Deficiencies in detention conditions and violence, however, subvert this right.
      When this occurs, proper medico-legal investigations are critical irrespective of
      the nature of death. Unfortunately, the very context of custody raises serious
      concerns over the effectiveness and fairness of medico-legal examinations. The
      aim of this manuscript is to identify and discuss the practical and ethical
      difficulties encountered in the medico-legal investigation following deaths in
      custody. Data for this manuscript come from a larger project on Death in Custody
      that examined the causes of deaths in custody and the conditions under which
      these deaths should be investigated and prevented. A total of 33 stakeholders
      from forensic medicine, law, prison administration or national human rights
      administration were interviewed. Data obtained were analyzed qualitatively.
      Forensic experts are an essential part of the criminal justice process as they
      offer evidence for subsequent indictment and eventual punishment of perpetrators.
      Their independence when investigating a death in custody was deemed critical and
      lack thereof, problematic. When experts were not independent, concerns arose in
      relation to conflicts of interest, biased perspectives, and low-quality forensic
      reports. The solutions to ensure independent forensic investigations of deaths in
      custody must be structural and simple: setting binding standards of practice
      rather than detailed procedures and relying on preexisting national practices as
      opposed to encouraging new practices that are unattainable for countries with
      limited resources. 

PMID- 24931859
TI  - Evidence based practice: laboratory feedback informs forensic specimen collection
      in NSW.
AB  - The importance of having clear, evidence-based guidelines for the taking of
      forensic samples from suspects detained in police custody (persons of interest)
      and complainants of crime is essential for forensic practitioners. The need for
      such guidelines was seen as desirable in New South Wales (NSW) and a working
      group was set up comprising scientists, practitioners and police. Feedback from
      the laboratory regarding the results of the specimens taken by forensic
      practitioners throughout the State was received and analysed. This has resulted
      in changes to current practice and highlighted the need for further research in
      this area. It has also highlighted areas that have not changed in response to
      evidence A quality service demands transparency, process review, relevant
      research and feedback in order to progress. Examiners need to obtain the results
      for their cases in order to reinforce the value of the service they provide as
      well as to monitor and, where necessary, improve their forensic collection
      skills. 

PMID- 24931860
TI  - Teaching forensic medicine in the University of Porto.
AB  - The University of Porto (UP) provides education in Forensic Medicine (FM) through
      the 1st, 2nd and 3rd cycle of studies, post-graduation and continuing education
      courses. This education is related to forensic pathology, clinical forensic
      medicine (including forensic psychology and psychiatry), forensic chemistry and
      toxicology, forensic genetics and biology, and criminalistics. With this work we
      intent to reflect on how we are currently teaching FM in the UP, at all levels of
      university graduation. We will present our models, regarding the educational
      objectives, curricular program and teaching/learning methodologies of each cycle
      of studies as well as in post-graduate and continuing education courses.
      Historically, and besides related administratively to the Ministry of Justice,
      the Portuguese Medico-Legal Institutes (since 1918) and more recently the
      National Institute of Legal Medicine and Forensic Sciences (INMLCF) also have
      educational and research responsibilities. Thus, it lends space and cooperates
      with academic institutions and this contribution, namely regarding teaching
      forensic sciences in Portugal has been judged as an example for other Countries.
      This contribution is so important that in UP, the Department of Legal Medicine
      and Forensic Sciences of the Faculty of Medicine (FMUP) shares, until now, the
      same physical space with North Branch of the INMLCF, which represents a notorious
      advantage, since it makes possible the "learning by doing". 

PMID- 24931861
TI  - Histopathological detection of entry and exit holes in human skin wounds caused
      by firearms.
AB  - The judiciary needs forensic medicine to determine the difference between an
      entry hole and an exit hole in human skin caused by firearms for civilian use.
      This important information would be most useful if a practical and accurate
      method could be done with low-cost and minimal technological resources. Both
      macroscopic and microscopic analyses were performed on skin lesions caused by
      firearm projectiles, to establish histological features of 14 entry holes and 14
      exit holes. Microscopically, in the abrasion area macroscopically observed, there
      were signs of burns (sub-epidermal cracks and keratinocyte necrosis) in the
      entrance holes in all cases. These signs were not found in three exit holes which
      showed an abrasion collar, nor in other exit holes. Some other microscopic
      features not found in every case were limited either to entry holes, such as
      cotton fibres, grease deposits, or tattooing in the dermis, or to exit holes,
      such as adipose tissue, bone or muscle tissue in the dermis. Coagulative necrosis
      of keratinocytes and sub-epidermal cracks are characteristic of entry holes.
      Despite the small sample size, it can be safely inferred that this is an
      important microscopic finding, among others less consistently found, to define an
      entry hole in questionable cases. 

PMID- 24931862
TI  - Evaluation of a 'decontamination kit' in NSW.
AB  - Dedicated facilities of a high standard should be available for the examination
      of complainants and suspects where forensic samples are to be taken to ensure
      that the risk of contamination is kept to a minimum. The need for a
      decontamination kit came about because of the variable quality of examination
      facilities for complainants of sexual assault and suspects (persons of interest)
      within NSW. Overall the kit has been found to be useful and easy to use but there
      is still a need to increase awareness of its availability. 

PMID- 24931863
TI  - Detainees in Amsterdam, a target population of the Public Mental Health System?
AB  - The Forensic Medical Service of the Public Health Service offers health care to
      detainees in police cells in Amsterdam. This study describes the registered
      mental health, addiction and social problems and compares them to the self
      reported problems among a sample of detainees. Registers of the Forensic Medical
      Service are related to information from registers of police detention episodes. A
      general assessment of substance use, mental health and social problems is
      obtained by interviewing a sample of 264 detainees. The Forensic Medical Service
      was contacted in 24% of the 17,321 detention episodes. In 14% of the episodes
      mental or substance related disorders were observed. Within the sample 59% scored
      positively on indicators of substance abuse or mental health problems, 35% had
      additional social problems (debts, unemployment, housing). This proportion
      increased with age. It is concluded that substance abuse and mental health
      problems combined with social problems are highly prevalent among detainees,
      especially among the older ones. This urges for a close cooperation between
      Public Mental Health Care and Forensic Medical Services. 

PMID- 24931864
TI  - Novel psychoactive substance intoxication resulting in attempted murder.
AB  - A man in his twenties who had no previous history of violence, snorted large
      quantities of two substances he identified as 3-methoxyphencyclidine (3-MeO-PCP),
      and methylenedioxypyrovalerone (MDPV); both are recognised as novel psychoactive
      substances, or commonly described in the media as "legal highs". He also inhaled
      butane gas. He experienced vivid hallucinations and developed bizarre ideas.
      During this state of mind he stabbed his father multiple times and was arrested
      and charged with attempted murder. He had a previous history of drug induced
      psychosis and although he had some slight residual symptoms before he consumed
      the substances, these were not considered relevant to his criminal liability at
      the time of the offence. The hallucinations caused by the use of these substances
      took six weeks to completely recede. He was convicted of attempted murder and
      sentenced to four years in prison. 

PMID- 24931865
TI  - Homicide-suicide in Brescia County (Northern Italy): a retrospective study from
      1987 to 2012.
AB  - From January 1987 to December 2012, 19 homicide-suicide events were registered at
      the Brescia Institute of Forensic Medicine (Northern Italy), leading to 39 deaths
      (20 homicide victims and 19 suicide victims). The homicide victims were females
      in the total of the cases (100%), while perpetrators were exclusively males
      (100%). Only one event involved foreigners as both victim and perpetrator, all
      the other cases regarded Italian people. The average age was 37.3 years for the
      homicide victims and 41.57 years for the offenders. Perpetrators usually used a
      firearm both for murder (65%) and suicide (84%). In 66% of the cases the homicide
      suicide events occurred at home; homicide victims were strictly bound to their
      perpetrators (husband, boyfriend or ex boyfriend, father) in all the events. 

PMID- 24931866
TI  - Fatal attack by a juvenile tiger shark, Galeocerdo cuvier, on a kitesurfer in New
      Caledonia (South Pacific).
AB  - We present a case of a non-provoked fatal shark attack on a 15-year old male
      kitesurfer in New Caledonia. The victim lost his board and was pulled by the sail
      along the water surface in a reef passage when a shark attacked. The shark
      inflicted at least two bites on the left leg, including a severe one around the
      knee, resulting in a quick hypovolemic shock that was fatal. The analysis of one
      of these bites indicated that a 2.8 m TL (est. length) tiger shark was
      responsible for this attack. The features of the attack are consistent with those
      of a predator response to a surface feeding stimulus.

PMID- 24931867
TI  - Forensic examination of the mentally disabled sexual abuse complainant.
AB  - Individuals who have mental disabilities are more vulnerable to sexual abuse than
      the general population and even less likely to report the offence. Furthermore
      they face greater barriers if they wish to seek help, support or prosecution.
      Where abuse is alleged or suspected, a complainant with a mental disability will
      often have the capacity to decide whether they wish to undergo intimate forensic
      examination. However, in cases where the individual truly lacks capacity it must
      be decided on an case to case basis without assumption or preconception whether
      such an examination is truly in their best interests. This aim of this review is
      to discuss sexual offences against adults with mental disabilities and the
      identification and management of these individuals. 

PMID- 24931868
TI  - A rose by any other name.

PMID- 24931869
TI  - Intra-individual and inter-individual variation in breath alcohol
      pharmacokinetics: the effect of short-term variation.
AB  - Ten male and 8 female students underwent serial breath alcohol concentration
      (BrAC) measurements on a CAMIC Datamaster on two consecutive occasions, early
      evening and again the following morning. Subjects were fasted for 6 h before
      receiving alcohol as white wine (12.5% by volume) at doses of 38-45 g for males
      and 26-37 g for females, consumed over 10 min. Specific individual doses were
      calculated individually from height and weight (according to the Forrest Method)
      to give target C0 breath alcohol concentrations of 35 MUg/100 ml breath in males
      and 31 MUg/100 ml breath in females. BrAC versus time curves were constructed for
      each subject and the values of peak BrAC (Cmax), BrAC extrapolated at zero time
      (C0), time taken to reach peak (Tmax) and rate of elimination (beta) were
      recorded directly from the curves. Values of C0 taken from the BrAC-time curves
      varied widely, from 21 to 47 MUg/100 ml on visit 1 and from 22 to 45 MUg/100 ml
      on visit 2. Widmark Factors calculated from these C0 values averaged 0.74 (range,
      0.59-1.06) in males and 0.73 (range, 0.58-1.05) in females. Elimination rate was
      higher in the morning than evening in both males (7.4 versus 5.7 MUg/100 ml/h)
      and females (6.9 versus 5.8 MUg/100 ml/h). Elimination rates in males and females
      were not significantly different. Total body water, measured by electronic
      scales, averaged 58.7% (range, 56.6-63%) in males and 48.3% (range, 40.9-57.6%)
      in females. Widmark Factors calculated by various established mathematical
      methods were 0.73-0.77 in males and 0.61-0.64 in females.

PMID- 24931870
TI  - The use of interpreters in medical settings and forensic medical examinations in
      Australia: the relationship between medicine and linguistics.
AB  - Medical examinations are dependent on combining communication with professional
      competence. In the development of a global multicultural community with the use
      of multiple languages, doctors have become increasingly dependent on language
      facilitation such as interpreting and translation. Despite professional studies,
      the use of language facilitation with its associated problems has not been fully
      explored in graduate and post-graduate medical and forensic medical training.
      There may still be some lack of reciprocal understanding between the medical and
      linguistic fields, their ethics, obligations and limits although both fields and
      their ethical frameworks are closer related than might be expected. This article
      is a discussion that aims at providing a basic understanding of guidelines as to
      the origin and appropriate use of language interpretation in medical and forensic
      medical examinations. 

PMID- 24931871
TI  - Lessons from a decade of technical-scientific opinions in obstetrical litigation.
AB  - The authors aimed to assess the Portuguese circumstances concerning situations of
      medico-legal dispute in Obstetrics, evaluate the conclusions of technical
      scientific opinions and analyze their consequences. The analysis of all cases of
      Obstetrics medical responsibility examined in Medico-legal Council since the
      creation of the National Institute of Legal Medicine was performed. Technical
      scientific opinions of those files were examined according to the existence of a
      causal link and of infringement of the 'leges artis'. The most common reasons for
      dispute in Obstetrics were perinatal asphyxia (50%), traumatic injuries of the
      newborn (24%), maternal sequelae (19%) and issues related to prenatal diagnosis
      and/or obstetric ultrasound (5.4%). In the technical-scientific opinions of files
      examined, the existence of a causal link was established in 17.4%, and the
      infringement of the 'leges artis' was suggested in 15.5% of cases, numbers which
      have grown significantly over the years and which are particularly relevant in
      the proceedings of perinatal asphyxia and traumatic lesions of the newborn. In
      11% of cases the opinion was inconclusive due to the poor quality of the clinical
      process sent for analysis. These results highlight the impact that litigation can
      have on the professional activity and personal lives of obstetricians. It should
      alert them for the need to better fulfill medical clinical files in order to
      reduce or avoid medico-legal conflicts, as well as to the fact of the increasing
      practice of defensive medicine and its consequences in daily clinical routine for
      doctors and patients. 

PMID- 24931872
TI  - When range of motion is not enough: towards an evidence-based approach to medico
      legal reporting in whiplash injury.
AB  - Whiplash injury medico-legal reporting has traditionally been focused upon
      identifying restrictions in range of motion and identifying the presence of
      tender areas in the cervical spine in an effort both to diagnose the condition
      and to offer a prognosis. There have been considerable advances in this field
      over the last decade however that calls into question such a diminutive approach.
      This paper reviews the contemporary evidence base for the medico-legal assessment
      of whiplash injury and identifies a body of literature that strongly implicates a
      Claimant's physiological and psychological stress response as a key medico-legal
      marker in predicting prognosis following whiplash injury. 

PMID- 24931873
TI  - Modeling sunscreen-mediated melanoma prevention in the laboratory opossum
      (Monodelphis domestica).

PMID- 24931874
TI  - Differences between nurses' and care workers' estimations of pain prevalence
      among older residents.
AB  - A high prevalence of pain and difficulties with pain assessment has been widely
      reported among residents of long-term-care facilities. We explored nurses' and
      care workers' estimations of residents' pain (both general and chronic) and the
      number of residents with unknown pain status. We also examined the relationship
      between the prevalence of pain and assessment strategies undertaken by nurses and
      care workers. A cross-sectional design was used. Nurses and care workers across
      750 long-term care facilities in four Japanese prefectures were asked to
      participate. Questionnaires were administered to one nurse and care worker at
      each facility. The questionnaires assessed the estimated numbers of residents who
      had pain in general, chronic pain, or unknown pain status on the day of data
      collection, and pain assessment strategies use by the health care professionals.
      In all, 263 (17.5%) questionnaires were returned from 147 nurses (55.9%) and 116
      care workers (44.1%). The nurses' and care workers' median estimations of pain
      and chronic pain prevalence among residents were 11.6 and 9.4 and 29.4 and 15.5,
      respectively (p < .001). Estimations of pain prevalence were significantly higher
      among nurses who had observed signs of pain among residents in the previous month
      (p = .04) and who applied a multidisciplinary approach to pain assessment and
      management (p = .007) than among nurses who did not do either. Nurses and care
      workers had relatively low estimations of the prevalence of pain among their
      residents. Staff should undertake appropriate and sufficient pain assessments in
      order to improve their understanding of residents' pain.

PMID- 24931875
TI  - The depletion of securin enhances butein-induced apoptosis and tumor inhibition
      in human colorectal cancer.
AB  - Butein (3,4,2',4'-tetrahydroxychalcone) is a promising natural polyphenolic
      compound that shows the growth inhibitory activity in human cancer cells;
      however, the precise mechanism is still unclear. Securin plays pivotal role in
      cancer cell proliferation and tumorigenesis. Here, we report the presence of
      securin that could modulate apoptosis and tumor growth ability in the butein
      treated human colorectal cancer. Butein induced caspase-3 activation and PARP
      protein cleavage for apoptosis induction in human colorectal cancer cells.
      Interestingly, butein reduced the securin protein levels but conversely increased
      the phospho-histone H3 proteins, mitotic arrest and abnormal chromosomes
      segregation in cancer cells. The securin-null colorectal cancer cells were more
      sensitive on the reduction of cell viability than the securin-wild type cancer
      cells following butein treatment. The loss of securin in human colorectal cancer
      cells decreased tumor growth ability in nude mice. Moreover, butein reduced the
      tumor size of xenografted human colorectal tumors of nude mice. Taken together,
      this study demonstrates for the first time that the depletion of securin mediates
      the butein-induced apoptosis and colorectal tumor inhibition. 

PMID- 24931876
TI  - Effect of TiO2 nanoparticles on the structure and activity of catalase.
AB  - TiO2 nanoparticles are the most widely used metal oxide nanoparticles and have
      oxidative toxicity. Catalase is an important antioxidant enzyme. Here the
      understanding of an effect of TiO2 nanoparticles on the activity and structure of
      catalase is crucial to characterize the toxicity of TiO2 nanoparticles. These
      experimental data revealed that TiO2 nanoparticles could bind to catalase by the
      electrostatic and hydrogen bonding forces. On binding TiO2 nanoparticles,
      catalase got destabilized with the decrease of alpha-helices content, the solvent
      polarity of environment around the fluorescence chromophores on catalase were
      also affected. In addition, TiO2 nanoparticles also affected the activity of
      catalase. TiO2 nanoparticles acted as an activator of catalase activity at a low
      molar concentration and as an inhibitor at a higher molar concentration. With
      regard to human health, the present study could provide a better understanding of
      the potential nanotoxicity of TiO2 nanoparticles.

PMID- 24931880
TI  - Editorial.

PMID- 24931877
TI  - [Formula: see text]inadequate effort on neuropsychological evaluation is
      associated with increased healthcare utilization.
AB  - Patients who exert inadequate effort on neuropsychological examination might not
      receive accurate diagnoses and recommendations, and might not cooperate fully
      with other aspects of healthcare. This study examined whether inadequate effort
      is associated with increased healthcare utilization. Of 355 patients seen for
      routine, clinical neuropsychological examination at a VA Medical Center, 283
      (79.7%) showed adequate effort and 72 (20.3%) showed inadequate effort, as
      determined at time of evaluation using the Word Memory Test and/or Test of Memory
      Malingering. Utilization data included number of Emergency Department (ED) visits
      and inpatient hospitalizations in the year following evaluation. Patients who had
      shown inadequate effort on examination had more Emergency Department visits, more
      inpatient hospitalizations, and more days of inpatient hospitalization in the
      year after evaluation, compared to patients who had exerted adequate effort. This
      finding was not attributable to group differences in age or medical/psychiatric
      comorbidities. Thus, patients who exerted inadequate effort showed greater
      healthcare utilization in the year following evaluation. Such patients might use
      more resources since diagnostic evaluations are inconclusive. Inadequate effort
      on examination might also serve as a "marker" for more general failure to
      cooperate fully in one's healthcare, possibly resulting in greater utilization. 

PMID- 24931881
TI  - Higher cardiovascular mortality with sertindole in ADROIT: a signal not
      confirmed.
AB  - Data from the Adverse Drug Reactions On-line Information Tracking (ADROIT)
      database, which records spontaneously reported adverse drug reactions (ADRs),
      suggested that the atypical antipsychotic, sertindole, might cause serious
      cardiac ADRs and be associated with a higher mortality rate than other atypicals.
      As sertindole was known to have the potential to cause QT interval prolongation,
      it was assumed to be responsible for the cardiac ADRs and apparently high death
      rate. During the ensuing CPMP deliberations, Lundbeck decided to withdraw
      sertindole from the market in 1998, pending further safety analyses. The ADROIT
      database, by design, is only suited for alert generation and not for hypothesis
      testing. Therefore, post-marketing observational studies providing valuable
      information on the effects of new drugs in real-life clinical practice, as well
      as long-term tolerability data, are necessary to evaluate a signal from the
      ADROIT database. In the case of sertindole, such studies did not substantiate the
      decision to suspend the drug. Moreover, no difference in the mortality rates has
      been observed for low- and high-risk patients. In conclusion, appropriately used,
      sertindole will provide yet another treatment option for patients with
      schizophrenia. 

PMID- 24931882
TI  - Patient satisfaction after switching from conventional to new atypical
      antipsychotics in schizophrenia.
AB  - OBJECT: To study the satisfaction and subjective experiences of patients with
      schizophrenia after switching from a conventional to a new atypical
      antipsychotic, and the relationship of patient satisfaction to clinical
      improvement METHOD: Seventy-four chronic schizophrenia (DSM-IV) patients in a
      naturalistic setting whose response to a conventional antipsychotic was
      unsatisfactory (clinical improvement or intolerance of side-effects) switched to
      olanzapine or quetiapine or risperidone. After 3 months, patients completed a
      seven-item Patient Satisfaction Questionnaire, and a psychiatrist assessed the
      clinical global improvement. RESULTS: Forty-five (61%) of the patients were
      either very or extremely satisfied with the new medication and 47 (63.5%) rated
      it very or extremely helpful; 35 (47%) of the patients reported no side-effects.
      Fiftyone (69%) indicated that they preferred the new medication to previous
      therapy: better tolerability was given as the reason by 40 (54%) patients. Fifty
      eight (78%) patients perceived a general improvement in their quality of life.
      Slightly fewer patients reported improvement in their symptoms and their daily
      living activities. Over 75% of patients expressed readiness to continue the new
      medication. Significant association between clinical response and patient
      satisfaction was demonstrated by only a small subgroup of patients. CONCLUSIONS:
      In the majority of schizophrenia patients, administration of new atypical
      antipsychotics seemed to result in higher levels of patient satisfaction than did
      conventional drugs. This had a favourable effect on the patients' attitude to the
      new medication, which may improve compliance. More patients perceived benefits
      related to quality of life than to efficacy. Clinical improvement was an
      important, but not the sole, determinant of patient satisfaction with medication.

PMID- 24931883
TI  - Sertindole: cardiac electrophysiological profile.
AB  - QT interval prolongation is the ECG correlate of prolongation of the cardiac
      action potential (AP). Abnormal or excessive QT interval prolongation may be
      associated with an increased risk of ventricular tachycardia. This association
      appears increasingly evident in congenital long QT syndrome and with certain
      classes of cardiovascular and non-cardiovascular therapeutics. Almost all drugs
      causing QT interval prolongation inhibit the rapid component of the delayed
      rectifier potassium current (I Kr ), an ion channel involved in the termination
      of the myocardial AP. Inhibition of I Kr leads to AP and QT interval
      prolongation. Drugs, which do not encounter a sufficient electrophysiological
      counterbalance to the inhibitory effect on I Kr , may thus impose a risk of
      ventricular tachyarrhythmia. Some non-cardiac drugs, including the antipsychotic
      sertindole, have inhibitory effects on I Kr but, in contrast to the drugs that
      are known to cause tachyarrhythmia, sertindole possesses an important
      electrophysiological counterbalancing profile. Sertindole inhibits &#102 1 
      adrenoceptors and blocks both sodium and calcium channels. The balanced
      electrophysiological profile of sertindole may well explain the low proarrhythmic
      potential observed in animal proarrhythmia models against positive comparators.
      It also supports the lack of increased cardiac mortality observed in clinical
      trials with sertindole and in large epidemiological studies. 

PMID- 24931884
TI  - Reported sleep patterns in obsessive compulsive disorder (OCD).
AB  - INTRODUCTION: Previous studies of sleep disturbance in OCD have produced
      contradictory findings. This may be due to different methodological approaches
      but may also reflect the fact that many studies have not screened OCD patients
      for depressive symptoms. This is particularly important since major depression is
      well known to disrupt sleep. METHOD: The current study examined 94 subjective
      reports of sleep as measured by the Pittsburgh Sleep Quality Index (PSQI). Twenty
      four OCD patients with and without co-morbid depression ( n =12 in each group)
      were compared with a group of normal subjects ( n =57) and a group of subjects
      with major depression ( n =13). RESULTS: In general, the OCD patients with co
      morbid depression exhibited very similar sleep patterns to the group with major
      depression. By contrast, those OCD patients without depressive symptoms showed
      similar sleep patterns to the group of normal subjects. Thus, contrary to some
      earlier studies, these data suggest that OCD does not generally influence
      reported sleep patterns unless there is a co-morbid diagnosis. However, a few non
      depressed OCD patients did report sleep phase shifting, suggesting that a small
      proportion may have abnormal sleep parameters. CONCLUSION: Such anomalies may be
      masked by group analyses and further case studies are therefore warranted to
      investigate whether such patients exhibit abnormal scores on biological sleep
      markers.

PMID- 24931885
TI  - Sertindole: a clinical efficacy profile.
AB  - Sertindole is an effective atypical antipsychotic drug that is associated with
      significant improvements in the symptoms of schizophrenia. It is at least as
      efficacious as haloperidol and risperidone in treating the overall and positive
      symptoms of schizophrenia and has been shown to have advantages over these two
      drugs with respect to the treatment of the negative symptoms of schizophrenia. In
      clinical trials, notable improvements in patients' quality of life were observed,
      which suggest that patients prescribed sertindole would be more likely to adhere
      to treatment and continue taking the drug as part of their long-term treatment
      regimen. Continued treatment gives patients the best chance of avoiding relapse.
      Indeed, other benefits of sertindole demonstrated in clinical trials include
      relatively low relapse and re-admission rates. Sertindole could theoretically
      reduce the financial burden of schizophrenia on health- and social-care systems
      by reducing the need for re-hospitalization and by enabling patients to manage
      their illness and to live as normal a life as possible. 

PMID- 24931886
TI  - Paroxetine versus amitriptyline in patients with recurrent major depression: A
      double-blind trial.
AB  - INTRODUCTION: Long-term exposure to antidepressants is required to prevent
      relapses and recurrences in patients with recurrent major depression.
      Furthermore, a good pharmacological compliance is the key to successful long-term
      treatment. Since the early phases of a treatment influence long-term compliance
      and compliance is adversely affected by poorly tolerated treatments, efficacy and
      tolerability of paroxetine and amitryptiline over 12 weeks were compared as an
      introduction to the issue of long-term compliance to these two agents. METHOD: A
      12-week, randomized, double-blind, doubledummy, parallel-group trial which
      involved 129 patients with recurrent major depression. RESULTS: Both paroxetine
      and amitriptyline were effective in controlling the symptoms of depression, as
      shown by the reduction in HAMD total score and CGI severity-of-illness score at
      endpoint compared to baseline. There was no statistically or clinically
      significant difference between the two treatments in terms of efficacy. However,
      marked numerical differences were noted in tolerability: the percentage of
      patients who reported treatment-emergent adverse experiences was greater in the
      amitriptyline group (40.0% vs 28.1%). This difference was mainly due to
      anticholinergic adverse events, which were six times more frequent with
      amitriptyline than with paroxetine. CONCLUSION: When compared with amitriptyline,
      paroxetine should allow patients with recurrent major depression to receive an
      equally effective treatment with a relatively lower incidence of adverse
      experiences.

PMID- 24931887
TI  - Sertindole: safety and tolerability profile.
AB  - Sertindole is a novel generation or atypical antipsychotic drug that has recently
      been re-introduced to the market. The safety and tolerability profile of
      sertindole have demonstrated a positive benefit/risk ratio in clinical trials and
      post-marketing studies. The number of patients who experienced extrapyramidal
      symptoms (EPS) while taking sertindole in clinical trials was similar to that of
      patients on placebo, and significantly less than that of patients on haloperidol.
      The relative lack of EPS is probably the result of the drug's highly selective
      blockade of limbic dopamine D 2 receptors and its lack of effect on other
      dopamine D 2 receptors, but may be due to low occupancy at dopamine D 2 striatal
      receptors. Sertindole also has a high affinity for serotonin 5-HT 2 and &#102 1
      receptors. It has been shown not to cause sedation and its propensity to cause
      anticholinergic side effects is low, probably due to its lack of antihistamine
      and antimuscarinic activity. Sertindole does not cause any clinically significant
      changes in serum prolactin levels. QT interval prolongation does occur in some
      patients. The sertindole mortality rate is comparable to that of both risperidone
      and olanzapine (1.46, 1.75 and 1.20, respectively). Overall, sertindole is a well
      tolerated drug that does not cause EPS, sedation or hyperprolactinaemia. 

PMID- 24931888
TI  - Gender differences in major depressive disorder in a Hungarian community survey.
AB  - INTRODUCTION: The aim of this study was to investigate the characteristics of
      Major Depressive Disorder (MDD) in males and females in a sample of the Hungarian
      adult population. METHOD: 2953 randomly selected subjects between 18 and 64 years
      old were interviewed using the Hungarian version of the Diagnostic Interview
      Schedule (DIS), which generated DSM-III-R diagnoses. RESULTS: The lifetime and
      period prevalences of MDD were more than twice as high in women than in men. The
      gender difference appeared in early adolescence and continued up until the age of
      50. An increased risk for anxiety disorders was found in patients with MDD,
      irrespective of gender, and in the majority of cases (65%) the anxiety symptoms
      preceded the onset of MDD. Depressed women tended to have more symptoms and a
      more marked tendency for recurrence than men. The preponderance of females was
      twice as high in MDD with comorbid anxiety than in MDD without it, in spite of
      the fact that the likelihood of the coexistence of MDD and anxiety disorders did
      not differ by gender. CONCLUSION: The higher MDD prevalence rate in women might
      be the consequence of a higher rate of pre-existing anxiety disorder(s).

PMID- 24931889
TI  - Post-marketing surveillance of sertindole.
AB  - The atypical antipsychotic drug, sertindole, like several other drugs, causes QT
      interval prolongation. Prolongation of the QT interval on the electrocardiogram
      has been associated with an increased risk of ventricular arrhythmia, including
      the more serious form, torsades de pointes, and is thus a safety concern for the
      authorities. In the case of sertindole, however, the available
      pharmacoepidemiological studies gathering data from about 10 000 patients
      documented the lack of increased risk associated to sertindole in comparison to
      other atypical antipsychotics. On the basis of these data, as well as non
      clinical and clinical safety data, the CPMP expert group concluded that, although
      sertindole has the potential to prolong the QT interval, &#164 &#164 QT interval
      prolongation does not seem to be a reliable proxy for the risk of severe cardiac
      arrhythmias'', and there are no clinical data suggesting that sertindole is more
      arrhythmogenic than are other atypical antipsychotics. To further substantiate
      this conclusion, two post-marketing surveillance studies have been initiated. One
      is a randomized comparison of sertindole and risperidone under normal conditions
      of use. Randomization minimizes selection bias and the intention is that
      allocation to the two treatment arms will yield comparable treatment groups.
      While the two drugs will be given in an open-label fashion, all safety data will
      be blinded and reviewed by an independent safety committee. The other study is an
      observational study that includes all patients prescribed sertindole who, for
      whatever reason, will not be included in the randomized study. In all, 10 000
      patients are expected to take part in the studies, which will run for at least 1
      year. 

PMID- 24931890
TI  - Month of birth and suicide: An exploratory study.
AB  - OBJECTIVE: To explore the association between suicide and month of birth. METHOD:
      Data were extracted from records of the Public Health Department in North
      Cheshire between 1989 and 2000. &#164 Suicide' refers to all deceased who were
      the subjects of coroner's inquests resulting in a verdict of suicide or an open
      verdict. The month of birth of all who died of natural causes and were reported
      during a 2-year period was obtained from the Public Health Department in North
      Cheshire for comparison. RESULTS: There were 502 incidents of suicide in North
      Cheshire during the 12-year period. Significant differences were found between
      suicides and deaths due to natural causes, with an increase of incidents of
      suicide in those born in the month of May ( &#104 2 23, d.f.11, P < 0.01). The
      distribution of suicide by hanging appeared to be significantly higher in those
      born in September and July and lowest in those born in November compared with
      what would expected by chance ( &#104 2 28, d.f.11, P < 0.005). Those who died by
      violent means were more likely to have been born in the summer. The difference
      between the observed and expected numbers of suicides by methods other than
      hanging failed to reach statistical significance. CONCLUSION: The results, though
      inconclusive, are interesting, particularly in view of recent reports that
      persons born during the winter &#45 spring months had significantly lower values
      of 5-HIAA, and also reports of low CSF levels of 5-HIAA in persons with violent
      suicidal behaviour such as hanging, stabbing, firearms, or jumping from heights
      and impulsivity. A biological explanation of suicidal behaviour could have
      implications for our understanding of the psychopathology of suicide and
      eventually offer new strategies for treatment and prevention. The conflicting
      reports from different countries within the northern hemisphere indicate the need
      for future studies with adequate design and acceptable statistical power.

PMID- 24931891
TI  - Fluvoxamine for the treatment of depression and parkinsonism in progressive
      supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a parkinsonian-like disorder
      characterized by postural instability, rigidity, bradykinesia, supranuclear
      ocular palsy, dysarthria, dysphagia and dementia. There is no satisfactory
      treatment. A 68-year-old woman with initial progressive supranuclear palsy is
      described, who was generally apathetic, withdrawn, lacked spontaneity in speech
      and behavior, and suffered episodes of depression. Treatment with
      levodopa/carbidopa was ineffective in controlling her parkinsonism and
      depression, but these symptoms responded to fluvoxamine. This response may be
      related to fluvoxamine's putative effect on the serotonin system. 

PMID- 24931892
TI  - Elective mutism: A case study.
AB  - We report a case of persistent elective mutism in a young single woman. To our
      knowledge there has been no published study or case report of persistent elective
      mutism starting at the age of acquisition of language and persisting until she
      was 22. 

PMID- 24931893
TI  - Heroin-induced leucoencephalopathy misdiagnosed as psychiatric illness.
AB  - We present a patient with a background of psychiatric illness who was admitted to
      hospital with neurological symptoms and signs. Although the organic cause of the
      neurological disorder was extremely uncommon and hence not readily diagnosed, the
      signs clearly did not accord with the preexisting psychiatric diagnoses.
      Nevertheless, several clinicians attributed the cause of the disorder to mental
      illness, or drug side-effects. It is possible that patients suffering from mental
      illness may be assessed differently, perhaps due to prejudgement by clinicians. 

PMID- 24931895
TI  - Endoscopic biopsy samples of naive "colitides" patients: role of basal
      plasmacytosis.
AB  - BACKGROUND: Although it is usually not difficult to diagnose inflammatory bowel
      disease (IBD) on surgical resection specimens, difficulties sometimes arise in
      differentiating these entities from other forms of colitis on endoscopic biopsy
      specimens. Basal plasmacytosis is considered as an early feature of IBD colitis,
      but it is rare in non-IBD colitides. AIMS: We assessed the value of basal
      plasmacytosis as an individual variable in untreated patients with colitis.
      PATIENTS AND METHODS: Archival slides of patients with untreated colitis (66 IBD
      and 49 non-IBD) and 20 controls with complete (from the terminal ileum to the
      rectum) endoscopic biopsy sampling were evaluated blindly for the presence of
      basal plasmacytosis and a possible association with the presence of eosinophils
      in the same anatomical location. RESULTS: Overall, basal plasmacytosis was
      present in at least one anatomical segment in 58% of cases, and it was always
      present in patients with IBD, whereas it was sparsely found (9%) in patients with
      other colitides and in controls. Basal plasmacytosis in three or more segments
      had more than 80% probability for a patient to be classified as IBD, with the
      segmental distribution being different between ulcerative colitis and Crohn's
      disease. Additionally, basal plasmacytosis was always accompanied by eosinophils
      intermingled with plasma cells in the same anatomical position. CONCLUSION: As an
      individual feature, basal plasmacytosis (accompanied by eosinophils) is a strong
      feature suggesting IBD, particularly when present in three or more colonic
      segments. This fact may be useful in the evaluation of endoscopic biopsies from
      patients with "colitis".

PMID- 24931896
TI  - Draft genome sequence of Hydrogenovibrio marinus MH-110, a model organism for
      aerobic H2 metabolism.
AB  - Hydrogenovibrio marinus, an obligate chemolithoautotroph isolated from oceanic
      surface water, is a Knallgas bacterium that conserves energy by oxidizing H2 in
      the presence of O2. The strain possesses a periplasmic membrane-bound respiratory
      [NiFe]-hydrogenase with high O2 tolerance, hence is of great biotechnological
      importance in the development of H2-based technologies for a promising
      alternative energy. Here, we report the draft genome of H. marinus MH-110,
      providing genomic information on the biosynthesis of the hydrogenase, aerobic H2
      metabolism, and autotrophic carbon assimilation. 

PMID- 24931897
TI  - Tetratricopeptide repeat domain 7A (TTC7A) mutation in a newborn with multiple
      intestinal atresia and combined immunodeficiency.
AB  - In the past year, two centers reported autosomal recessive mutations in
      tetratricopeptide repeat domain 7A (TTC7A) gene in patients with multiple
      intestinal atresia and immunodeficiency. Here, we present clinical progress of an
      infant with multiple intestinal atresia and combined immunodeficiency who carries
      novel compound heterozygote mutations in TTC7A gene. 

PMID- 24931898
TI  - Development and validation of a HPLC-PDA bioanalytical method for the
      simultaneous estimation of Aliskiren and Amlodipine in human plasma.
AB  - A simple, unique and selective HPLC-PDA method was developed and validated for
      the simultaneous estimation of aliskiren (ALS) and amlodipine (AML) in human
      plasma. Extraction of the sample was accomplished by protein precipitation.
      Plasma proteins were precipitated by employing acetonitrile containing
      hydrochlorothiazide as internal standard. The compounds were analyzed by HPLC by
      using PDA detector on a Hibar C18 (250 * 4.6 mm) column with a mobile phase
      comprising acetonitrile and phosphate buffer (pH 4.2 and 25 mm; 60:40 v/v) with a
      flow rate of 0.8 mL/min. Different sample pretreatment techniques were evaluated
      but protein precipitation was found to be satisfactory, offering good recovery
      values of 97.11-98.45% for ALS and 97.5-99.12% for AML. The within-day precisions
      for ALS were 96.66, 99.16 and 99.41% at 90, 240 and 480 ng/mL, respectively, and
      for AML they were 97.27, 99.54 and 99.31% at 3.3, 8.8 and 17.6 ng/mL,
      respectively. The between-day precisions for ALS were 96.66, 99.16 and 99.41% at
      90, 240 and 480 ng/mL, respectively and the between-day precisions for AML were
      98.18, 99.20 and 99.40% at 3.3, 8.8 and 17.6 ng/mL, respectively. The limit of
      quantitation was 30 and 1.0 ng/mL for ALS and AML respectively. Different
      constituents of plasma proteins did not interfere with the absolute recovery of
      ALS and AML.

PMID- 24931899
TI  - Role of Presepsin (sCD14-ST) and the CURB65 scoring system in predicting severity
      and outcome of community-acquired pneumonia in an emergency department.
AB  - INTRODUCTION: CD14 is one of the leukocyte differentiation antigens, and is
      present in macrophages, monocytes, granulocytes and their cell membranes.
      Presepsin, namely soluble CD14-subtype (sCD14-ST) is produced by circulating
      plasma proteases activating cleavage of soluble CD14 (sCD14). The aim of this
      study is to investigate the role of Presepsin and the CURB65 scoring system in
      the evaluation of severity and outcome of CAP in an ED. METHOD: A prospective,
      observational study was performed in an ED of an university teaching hospital
      from November 2011 to October 2012. A total of 359 patients with CAP and 214
      patients with severe CAP (SCAP) were consecutively enrolled. Plasma Presepsin,
      lactate, serum PCT levels and leukocyte counts were measured and CURB65 score
      were calculated at admission enrollment. RESULT: Plasma Presepsin levels were
      significantly higher in SCAP patients than in CAP patients (P < 0.0001),
      increasing correspondingly with the enhancement of CURB65 score. Patients with
      ARDS or DIC had obviously higher plasma Presepsin levels than those without ARDS
      or DIC (all P < 0.0001), and plasma Presepsin levels were significantly higher in
      non-survivors than in survivors at 28-day follow-up. In logistic regression
      analysis, CURB65 score was the independent predictor of ARDS, and Presepsin was
      the independent predictor of DIC, and Presepsin and CURB65 score were both the
      independent predictors of 28-day mortality. The AUCs showed Presepsin in
      combination with CURB65 score in predicting ARDS, SCAP and 28-day mortality was
      superior to Presepsin or CURB65 score alone ( all P < 0.01), Presepsin was better
      than CURB65 score and leukocyte in predicting DIC ( P < 0.01). CONCLUSION:
      Presepsin is a valuable biomarker in predicting severity and outcome in CAP
      patients in the ED and Presepsin in combination with CURB65 score significantly
      enhanced the predictive accuracy.

PMID- 24931900
TI  - The effect of an outpatient care on-demand-system on health status and costs in
      patients with COPD. A randomized trial.
AB  - BACKGROUND: Traditionally, outpatient visits for COPD are fixed, pre-planned by
      the pulmonologist. This is not a patient centered method, nor, in times of
      increasing COPD prevalence and resource constraints, perhaps the optimal method.
      OBJECTIVES: This pilot study, determined the effect of an on-demand-system,
      patient initiated outpatient visits, on health status, COPD-related healthcare
      resource-use and costs. METHODS: Patients were randomized between on-demand
      system (n = 49) and usual care (n = 51), with a 2-year follow-up. Primary, health
      status was assessed with Clinical COPD Questionnaire (CCQ). Secondary endpoints
      were: St. George's Respiratory Questionnaire (SGRQ), Short Form-36 (SF-36)
      scores, visits to general practitioners (GP), pulmonologists, and pulmonary nurse
      practitioners (PNP), exacerbations and total treatment costs from healthcare
      providers and healthcare insurance perspectives. RESULTS: Participants had a mean
      FEV(1) 1.3 +/- 0.4 liters and were 69 +/- 9 years. CCQ total scores deteriorated
      in both groups, with no significant difference between them. CCQ symptom domain
      did show a significant and clinically relevant difference in favor of the on
      demand-group, -0.4 +/- 0.21, CI95% -0.87; -0.02, p = 0.04. Similar tendency was
      found for the SGRQ whereas results for SF-36 were inconsistent. Patients in the
      on-demand-group visited GP significantly less (p = 0.01), but PNP significantly
      more, p = 0.003. Visits to pulmonologists and exacerbations were equally frequent
      in both groups. Mean total costs per patient were lower in the on-demand-group in
      comparison with usual care, difference of ?-518 (-1993; 788) from healthcare
      provider and ?-458 (-2700; 1652) insurance perspective. CONCLUSIONS: The on
      demand-system was comparable with usual care, had a cost-saving tendency, and can
      be instituted with confidence in the COPD outpatient care setting.

PMID- 24931901
TI  - Implementing the legal provisions for HIA in Slovakia: an exploration of
      practitioner perspectives.
AB  - BACKGROUND: Health Impact Assessment (HIA) is an instrument used in many
      countries across the world to assess and report on negative and positive health
      impacts of projects, programmes and policies. It was included in the Protection,
      Support and Development of Public Health Act (355/2007) of the Slovak Republic in
      2007, thus legislating for HIA. Due to this novel move to legislate for HIA,
      exploratory research was conducted in order to inquire into the perceptions of
      key informants and practitioners of the upcoming enforcement of the HIA part of
      legislation (to take place from January 2011). This paper presents results from
      the survey of practitioners in the Slovak Regional Public Health Authorities.
      METHODS: A postal questionnaire was administered to the Heads of Environmental
      Health Departments of the 37 Regional Public Health Authorities. Open-ended
      questions were contained in the survey. The response rate was 38%. RESULTS:
      Results show that a number of respondents are uncertain as to how HIA would be
      implemented in practice, with varying views on the technical and institutional
      barriers to comprehensive implementation of HIA. CONCLUSION: Although the public
      hygiene and sanitation networks in the public health system in Slovakia operate
      smoothly, the readiness of the public health infrastructure for HIA, which is
      based broadly on the social model of health, is dubious. Although HIA is
      contained within legislation, time will tell whether its implementation in
      practice will be as comprehensive as is hoped. Recommendations for further
      integration of HIA into the public health system include further training and
      education, national HIA resource centres and cross-country support.

PMID- 24931902
TI  - Loss of GLUT4 induces metabolic reprogramming and impairs viability of breast
      cancer cells.
AB  - Metabolic reprogramming strategies focus on the normalization of metabolism of
      cancer cells and constitute promising targets for cancer treatment. Here, we
      demonstrate that the glucose transporter 4 (GLUT4) has a prominent role in basal
      glucose uptake in MCF7 and MDA-MB-231 breast cancer cells. We show that shRNA
      mediated down-regulation of GLUT4 diminishes glucose uptake and induces metabolic
      reprogramming by reallocating metabolic flux to oxidative phosphorylation. This
      reallocation is reflected on an increased activity of the mitochondrial oxidation
      of pyruvate and lower lactate release. Altogether, GLUT4 inhibition compromises
      cell proliferation and critically affects cell viability under hypoxic
      conditions, providing proof-of-principle for the feasibility of using
      pharmacological approaches to inhibit GLUT4 in order to induce metabolic
      reprogramming in vivo in breast cancer models.

PMID- 24931903
TI  - Repairing the ventral root is sufficient for simultaneous motor and sensory
      recovery in multiple complete cervical root transection injuries.
AB  - AIM: In multiple cervical root transection injuries, motor and sensory recovery
      has been demonstrated after repairing both dorsal and ventral roots with
      autologous grafts applied to the dorsal and ventral aspects, respectively.
      However, in clinical situations, autologous grafts may not be sufficient to
      repair both roots in this situation. In this study, the authors evaluated whether
      repairing ventral root alone is sufficient for simultaneous sensory and motor
      function recovery. MAIN METHODS: In the transected group, the left 6th-8th
      cervical roots were pulled and transected at the spinal cord junction. In the
      repair group, the transected root was anastomosed to a single autologous nerve
      graft, which was inserted into the ventral horn through a pial incision. Acidic
      fibroblast growth factor mixed with fibrin glue was applied to the surgical area.
      Motor function, sensory function, cortical somatosensory evoked potentials
      (SSEPs), axon tracing, and CGRP(+) fibers were evaluated. KEY FINDINGS: The
      repaired rats exhibited simultaneous sensory and motor function recovery. At the
      16th weeks, SSEPs reappeared in all animals of the repair group, but not in the
      transected group. Retrograde axon tracing demonstrated an increased number of
      sensory neurons in the dorsal root ganglia and regenerating nerve fibers in the
      dorsal horn. CGRP(+) fibers were significantly increased in the repair group and
      restricted to laminae I and II. SIGNIFICANCE: This is the first report that in
      multiple root avulsions with insufficient grafts, repairing ventral roots alone
      leads to both sensory recovery and motor recovery. This finding may help patients
      with multiple cervical root avulsions.

PMID- 24931904
TI  - Amino acid facilitates absorption of copper in the Caco-2 cell culture model.
AB  - AIM: Copper deficiency could cause fatal hematological and neurological disorders
      or other diseases. Amino acids are involved in the absorption of copper ions. The
      purpose of this study is to evaluate the absorption of copper in amino acid
      complex forms and determine its mechanism in the Caco-2 cell culture model. MAIN
      METHODS: The human colonic adenocarcinoma cell line Caco-2 culture model was used
      to determine the permeability of copper ions in inorganic form (CuSO4) and the
      amino acid complex forms. Lysine and methionine, as well as carboplatin were used
      to determine the possible involvement of amino acid transporters or copper
      transporter 1 (CTR1). KEY FINDINGS: The results showed that all of the amino acid
      complex forms facilitated copper absorption. The apparent permeabilities of
      copper ions in these complex forms were at least 7.6 fold higher than those in
      the CuSO4 form. The permeability rank order of copper in various amino acid
      complex forms was Cu-glutamate<Cu-lysine=Cu-aspartic acid=Cu methionine<Cu
      arginine<Cu-(lysine/glutamate). Mechanistic studies revealed that the enhanced
      absorption of copper in copper amino acid complexes could be the result of
      enhanced uptake (as in Cu-methionine complex) or enhanced basolateral efflux (as
      in Cu-lysine complex). Copper transporter 1 (or CTR1) inhibitor carboplatin did
      not affect the absorption of copper in Cu-methionine complex, suggesting that the
      dominant pathway for copper amino acid complexes is not CTR1. SIGNIFICANCE:
      Enhanced absorption of copper ions in amino acid complex appears to be mediated
      by amino acid transporters.

PMID- 24931905
TI  - Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the
      ghrelin mimetic RM-131.
AB  - AIMS: The 28 amino acid hormone ghrelin, the natural ligand for the growth
      hormone secretagogue, or ghrelin receptor (GHR), has diverse physiological
      functions, including a possible role as a gastrointestinal prokinetic. The
      synthetic ghrelin mimetic RM-131 is in Phase II clinical trials for treatment of
      diabetic gastroparesis and other gastrointestinal (GI) disorders. We aimed to
      determine the relative potency of RM-131, when compared to other GI ghrelin
      mimetics, to predict efficacy and determine the role of RM-131 in models of
      inflammatory bowel disease. MAIN METHODS: We evaluated and compared ghrelin, RM
      131 and other synthetic ghrelin mimetics for their prokinetic potency in models
      of gastrointestinal disorders in the rat and we evaluated the endocrine (rats and
      dogs) and anti-inflammatory effects (mice) of the ghrelin mimetic RM-131. KEY
      FINDINGS: The pentapeptide RM-131 increased gastric emptying in rodent models of
      ileus. RM-131 is about 100-fold more potent than human ghrelin and is 600 to 1800
      fold more potent, when compared to several investigational ghrelin mimetics
      tested in clinical trials. RM-131 has anti-inflammatory effects and significantly
      increases survival and reduces macroscopic markers of tissue damage in a TNBS
      model of inflammatory bowel disease. RM-131 treatment shows a transient increase
      in growth hormone levels in Beagle dogs and rats, returning to baseline upon
      chronic treatment. Significant effects on glucose and insulin are not observed in
      chronic studies. SIGNIFICANCE: RM-131's potency, efficacy and endocrine profile,
      are promising attributes for the treatment of diverse functional gastrointestinal
      disorders in humans.

PMID- 24931906
TI  - Selenium supplementation shows protective effects against patulin-induced brain
      damage in mice via increases in GSH-related enzyme activity and expression.
AB  - AIMS: This study was designed to investigate the protective effects of selenium
      supplementation on patulin-induced neurotoxicity. MAIN METHODS: Mice were
      subjected to patulin for 8 weeks. Sodium selenite (Na2SeO3) and selenium
      methionine (Se-Met) were supplemented with the diet, and we investigated the
      effects of selenium on patulin-induced neurotoxicity. The animals were randomly
      divided into 4 groups containing 6-8 mice each. The first group was used as a
      control, and only physiological saline (0.9%) was injected. The second group was
      treated with patulin (1mg/kg) intraperitoneally. The third group was treated with
      patulin (1mg/kg) along with a dietary supplementation of Na2SeO3 (0.2mg Se/kg of
      diet). The fourth group was treated with patulin (1mg/kg) plus Se-Met (0.2mg
      Se/kg of diet). KEY FINDINGS: Patulin treatment increased oxidative damage in the
      brain, as evidenced by a decrease in non-protein thiol and total thiol groups,
      along with significant increases in GSSG, reactive oxygen species, thiobarbituric
      acid reactive substances and protein carbonyl levels. Moreover, the activities of
      glutathione peroxidase (GPx) and glutathione reductase were inhibited with
      patulin treatment. Selenium supplementation significantly ameliorated these
      biological parameter changes. In addition, selenium treatments significantly
      increased the mRNA levels of GPx-1, GPx-4 and thioredoxin reductase.
      SIGNIFICANCE: Our data show that selenium supplementation increases the activity
      and expression of glutathione-related enzymes and offers significant protection
      against brain damage induced by patulin.

PMID- 24931907
TI  - In vivo effects of propyl gallate, a novel Ca(2+) sensitizer, in a mouse model of
      dilated cardiomyopathy caused by cardiac troponin T mutation.
AB  - AIMS: We have previously demonstrated that propyl gallate has a Ca(2+)
      sensitizing effect on the force generation in membrane-permeabilized (skinned)
      cardiac muscle fibers. However, in vivo beneficial effects of propyl gallate as a
      novel Ca(2+) sensitizer remain uncertain. In the present study, we aim to explore
      in vivo effects of propyl gallate. MAIN METHODS: We compared effects of propyl
      gallate on ex vivo intact cardiac muscle fibers and in vivo hearts in healthy
      mice with those of pimobendan, a clinically used Ca(2+) sensitizer. The
      therapeutic effect of propyl gallate was investigated using a mouse model of
      dilated cardiomyopathy (DCM) with reduced myofilament Ca(2+) sensitivity due to a
      deletion mutation DeltaK210 in cardiac troponin T. KEY FINDINGS: Propyl gallate,
      as well as pimobendan, showed a positive inotropic effect. Propyl gallate
      slightly increased the blood pressure without changing the heart rate in healthy
      mice, whereas pimobendan decreased the blood pressure probably through
      vasodilation via inhibition of phosphodiesterase and increased the heart rate.
      Propyl gallate prevented cardiac remodeling and systolic dysfunction and
      significantly improved the life-expectancy of knock-in mouse model of DCM with
      reduced myofilament Ca(2+) sensitivity due to a mutation in cardiac troponin T.
      On the other hand, gallate, a similarly strong antioxidant polyphenol lacking
      Ca(2+) sensitizing action, had no beneficial effects on the DCM mice.
      SIGNIFICANCE: These results suggest that propyl gallate might be useful for the
      treatment of inherited DCM caused by a reduction in the myofilament Ca(2+)
      sensitivity.

PMID- 24931908
TI  - Influence of inflammatory response, infection, and pulmonary function in cystic
      fibrosis.
AB  - AIMS: Recurrent infections and activation of the inflammatory response affect the
      prognosis of cystic fibrosis (CF). We investigated the relationship between
      inflammatory response, infection, and pulmonary function in CF. MAIN METHODS: A
      clinical-cross-sectional study was conducted with 86 subjects: control group (CG,
      n=31, the same age and sex of the CF group), and CF group (CFG, n=55, age: 1-16
      years), further distributed into CFG negative or positive bacteriology (CFGB(
      )/CFGB(+)), and CFG negative or positive Pseudomonas aeruginosa (CFGPa(
      )/CFGPa(+)). Using the Wald test, multiple linear regression (95% confidence
      interval) was performed between CG and CFG, and between CG and each of the CF
      subgroups (CFGB(-)/CFGB(+) and CFGPa(-)/CFGPa(+)). The inflammatory markers
      evaluated were myeloperoxidase (MPO), adenosine deaminase (ADA) activities,
      interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), C-reactive
      protein (CRP), nitric oxide metabolites (NOx) levels, and total and differential
      leukocyte counts. KEY FINDINGS: After adjusting for sex and age, CFG compared to
      CG revealed an increase of MPO, IL-1beta (P<0.001 in all subgroups), and CRP: CFG
      (P=0.002), CFGB(-) (P=0.007), CFGB(+) (P=0.009), CFGPa(-) (P=0.004) and CFGPa(+)
      (P=0.020). NOx (P=0.001, P<0.001), leukocytes (P=0.002, P=0.001), and neutrophils
      (P=0.003, P<0.001) were increased in CFGB(+) and CFGPa(+), respectively. A
      negative correlation between FEV1 and leukocytes (P=0.008) and FEV1 and
      neutrophils (P=0.031) resulted in CFG. SIGNIFICANCE: The inflammatory response
      characterized by the increase of MPO, IL-1beta, and CRP is determinant for CF.
      Also leukocytosis due to neutrophilia determines the pulmonary function
      deficiency in this disease.

PMID- 24931909
TI  - Management of clinical stage I nonseminomatous germ cell tumors.
AB  - Therapeutic options for clinical stage I nonseminomatous germ cell tumor include
      active surveillance, adjuvant chemotherapy and retroperitoneal lymph node
      dissection (RPLND). Lymphovascular invasion (LVI) determines risk of recurrence,
      as those without LVI have 15% risk of relapse on surveillance while those with
      LVI have a 50% risk. This stratifies patients into high risk(LVI+) and low
      risk(LVI-) groups which direct treatment recommendations. Surveillance is
      preferred for those with low risk disease, and is an option for those with high
      risk disease, as at least half are over-treated with other options. Adjuvant
      chemotherapy is an option for all patients as it can eradicate micrometastatic
      disease and reduce recurrence by at least 90%. RPLND benefits patients with low
      volume retroperitoneal disease with a cure rate of RPLND alone at approximately
      70%. All three treatment modalities have similar survival rates approaching 100%
      but differing potential morbidities, which, along with patient preferences and
      compliance, should guide treatment decisions. 

PMID- 24931911
TI  - Exercise-associated hyponatremia with exertional rhabdomyolysis: importance of
      proper treatment.
AB  - BACKGROUND: Proper acute management of exercise-associated hyponatremia (EAH) has
      been known for decades, yet this information has not been uniformly implemented.
      Since treatment of EAH with isotonic fluids can result in delayed recovery and
      death, it is important that proper acute management in the field and hospital be
      utilized. CASE REPORT: We describe a participant of the 161-km Western States
      Endurance Run (WSER) who presented with seizure after dropping out at 145 km. He
      had gained 2.2% of his initial weight by 126 km from using sodium supplements and
      drinking copious volumes of fluids. He was treated promptly in the field for
      presumed EAH with two intravenous boluses of 100 mL of 3% hypertonic saline and
      showed rapid improvement in neurologic status. His recovery was then delayed with
      the use of high volumes of intravenous isotonic fluids, apparently for concern
      over his mild exertional rhabdomyolysis. CONCLUSIONS: Symptomatic EAH should be
      acutely managed with hypertonic saline, whereas treatment with high volumes of
      isotonic fluids may delay recovery and has even resulted in deaths from cerebral
      edema. Concern over central pontine myelinolysis from rapid correction of
      hyponatremia in EAH is unsupported. Furthermore, the exertional rhabdomyolysis
      often associated with EAH, and the concern over progression to acute kidney
      failure, should not dictate initial treatment.

PMID- 24931912
TI  - Regioselective synthesis of 3,4,5-trisubstituted 2-aminofurans.
AB  - Three series of methyl 5-substituted 2-aminofuran-4-keto-3-carboxylates have been
      prepared following a multicomponent reaction strategy by the addition of an
      isocyanide to 4-oxo-2-butynoate in the presence of an aldehyde. The cycloaddition
      regioselectivity is generally high (>95%) but decreases when an electron-rich
      substituent is located at the butynoate 4-position. 

PMID- 24931910
TI  - sigma(N) -dependent control of acid resistance and the locus of enterocyte
      effacement in enterohemorrhagic Escherichia coli is activated by acetyl phosphate
      in a manner requiring flagellar regulator FlhDC and the sigma(S) antagonist FliZ.
AB  - In enterohemorrhagic Escherichia coli (EHEC), sigma factor N (sigma(N)) regulates
      glutamate-dependent acid resistance (GDAR) and the locus of enterocyte effacement
      (LEE); discrete genetic systems that are required for transmission and virulence
      of this intestinal pathogen. Regulation of these systems requires nitrogen
      regulatory protein C, NtrC, and is a consequence of NtrC-sigma(N) -dependent
      reduction in the activity of sigma factor S (sigma(S)). This study elucidates
      pathway components and stimuli for sigma(N)-directed regulation of GDAR and the
      LEE in EHEC. Deletion of fliZ, the product of which reduces sigma(S) activity,
      phenocopied rpoN (sigma(N)) and ntrC null strains for GDAR and LEE control, acid
      resistance, and adherence. Upregulation of fliZ by NtrC-sigma(N) was shown to be
      indirect and required an intact flagellar regulator flhDC. Activation of flhDC by
      NtrC-sigma(N) and FlhDC-dependent regulation of GDAR and the LEE was dependent on
      sigma(N)-promoter flhDP 2 , and a newly described NtrC upstream activator
      sequence. Addition of ammonium chloride significantly altered expression of GDAR
      and LEE, acid resistance, and adherence, independently of rpoN, ntrC, and the
      NtrC sensor kinase, ntrB. Altering the availability of NtrC phosphodonor acetyl
      phosphate by growth without glucose, with acetate addition, or by deletion of
      acetate kinase ackA, abrogated NtrC-sigma(N)-dependent control of flhDC, fliZ,
      GDAR, and the LEE.

PMID- 24931913
TI  - Heterogeneously porous gamma-MnO2-catalyzed direct oxidative amination of
      benzoxazole through C-H activation in the presence of O2.
AB  - Oxidative amination of azoles through catalytic C-H bond activation is a very
      important reaction due to the presence of 2-aminoazoles in several biologically
      active compounds. However, most of the reported methods are performed under
      homogeneous reaction conditions using excess reagents and additives. Herein, we
      report the heterogeneous, porous gamma-MnO2-catalyzed direct amination of
      benzoxazole with wide range of primary and secondary amines. The amination was
      carried under mild reaction conditions and using molecular oxygen as a green
      oxidant, without any additives. The catalyst can easily be separated by
      filtration and reused several times without a significant loss of its catalytic
      performance. Of note, the reaction tolerates a functional group such as alcohol,
      thus indicating the broad applicability of this reaction.

PMID- 24931914
TI  - Clinical features of cerebral palsy in children with symptomatic congenital
      cytomegalovirus infection.
AB  - BACKGROUND: Human cytomegalovirus is the most common cause of vertically
      transmitted viral infection, affecting around 1% of liveborns. Infection is
      symptomatic in nearly 10% of infected children who are at higher risk of
      development of severe neurological disorders, including cerebral palsy. AIMS: To
      study the clinical profile of children with cerebral palsy caused by symptomatic
      congenital cytomegalovirus infection in a multicenter study involving six
      countries from the Surveillance of Cerebral Palsy in Europe (SCPE) Network.
      METHODS: Data on 35 children (13 males, 22 females; mean age at last assessment
      12y 6mo, age range 14y 6mo, min 4y, max 18y 6mo) on pre/peri/neonatal history and
      last clinical assessment were collected. Classification of cerebral palsy and
      associated impairments was performed according to SCPE criteria. RESULTS: The
      majority of children had bilateral spastic cerebral palsy, 85.7%, with a
      confidence interval (CI) [69.7-95.2], and 71.4% [CI 53.7-85.4] were unable to
      walk (GMFCS levels IV-V) while fine motor function was severely affected in 62.8%
      [CI 44.9-78.5] (BFMF levels IV and V). Most of the children with severe CP had
      severe associated impairments. 11.4% of children had severe visual and 42.8%
      severe hearing impairment, 77.1% [CI 59.9-89.6] suffered from epilepsy, also
      77.1% had severe intellectual impairment, and speech was undeveloped in 71.4%.
      Female:male ratio was 1.69:1 and 80% of children were term born. CONCLUSIONS:
      Cerebral palsy following symptomatic congenital cytomegalovirus infection seems
      to be in most cases a severe condition and associated impairments are
      overrepresented.

PMID- 24931915
TI  - Relevance of intraglandular injections of Botulinum toxin for the treatment of
      sialorrhea in children with cerebral palsy: a review.
AB  - BACKGROUND: After the age of 4 years, drooling becomes pathological and impacts
      the quality of life of children with cerebral palsy. Intraglandular injection of
      Botulinum toxin is one of the treatments available to limit this phenomenon.
      AIMS: The objectives of this review were to validate the efficacy of Botulinum
      toxin injections for drooling in children with cerebral palsy, determine
      recommendations and identify potential side effects. METHODS: We conducted a
      literature review from 2001 in the following databases: Embase, Pubmed and
      Cochrane using the keywords: sialorrhea, drooling, hypersalivation, Botulinum
      toxin, cerebral palsy and children. Only the articles evaluating the efficacy of
      Botulinum toxin in children with cerebral palsy over the age of 4 were
      researched. RESULTS: Eight studies were found: 2 case studies, 3 open and non
      controlled studies and 3 randomized controlled trials. Efficacy results in this
      indication are quite encouraging and the use of BTX injections is safe but the
      overall level of evidence of these studies was quite low. CONCLUSION: However,
      intraglandular injection of Botulinum toxin has a place among the therapeutic
      array available for the management of sialorrhea in this population even if no
      standardized protocol is available yet.

PMID- 24931917
TI  - The bending machine: CO2 activation and hydrogenation on delta-MoC(001) and beta
      Mo2C(001) surfaces.
AB  - The adsorption and activation of a CO2 molecule on cubic delta-MoC(001) and
      orthorhombic beta-Mo2C(001) surfaces have been investigated by means of periodic
      density functional theory based calculations using the Perdew-Burke-Ernzerhof
      exchange-correlation functional and explicitly accounting for (or neglecting) the
      dispersive force term description as proposed by Grimme. The DFT results indicate
      that an orthorhombic beta-Mo2C(001) Mo-terminated polar surface provokes the
      spontaneous cleavage of a C-O bond in CO2 and carbon monoxide formation, whereas
      on a beta-Mo2C(001) C-terminated polar surface or on a delta-MoC(001) nonpolar
      surface the CO2 molecule is activated yet the C-O bond prevails. Experimental
      tests showed that Mo-terminated beta-Mo2C(001) easily adsorbs and decomposes the
      CO2 molecule. This surface is an active catalyst for the hydrogenation of CO2 to
      methanol and methane. Although MoC does not dissociate C-O bonds on its own, it
      binds CO2 better than transition metal surfaces and is an active and selective
      catalyst for the CO2 + 3H2 -> CH3OH + H2O reaction. Our theoretical and
      experimental results illustrate the tremendous impact that the carbon/metal ratio
      has on the chemical and catalytic properties of molybdenum carbides. This ratio
      must be taken into consideration when designing catalysts for the activation and
      conversion of CO2. 

PMID- 24931916
TI  - Lymphatic and blood vasculature in primary cutaneous melanomas of the scalp and
      neck.
AB  - BACKGROUND: Scalp/neck melanomas have a poor prognosis, possibly because of a
      rich vascular supply that prompts tumor cells' dissemination. METHODS: We
      compared the accuracy of immunohistochemical (IHC) staining with morphology for
      the identification of lymphovascular invasion in 156 scalp/neck melanomas. We
      then analyzed the association of vessel invasion and density with pathological
      features and survival. RESULTS: IHC-detected lymphatic vessel invasion (LVI) and
      blood vessel invasion (BVI) were identified in 34.6% and 13.5% of cases,
      respectively. IHC increased the LVI/BVI detection compared to morphology (40.4%
      vs 16.6%; p < .001). The degree of peritumoral and intratumoral blood vessel
      density (BVD) was greater than lymphatic vessel density (LVD). Ulceration was the
      only factor independently associated with intratumoral (p = .029) and peritumoral
      (p = .047) BVD. Tumor thickness was the only independent predictor of survival (p
      = .002). CONCLUSION: IHC allows accurate assessment of lymphovascular invasion in
      scalp/neck melanomas. In these tumors, we observed a high incidence of BVI, which
      deserves further investigations.

PMID- 24931918
TI  - Tigecycline therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP)
      bacteriuria leads to tigecycline resistance.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasing global threat.
      Here, we describe the prevalence and impact of tigecycline use in a cohort of
      patients with CRKP bacteriuria nested within a multicentre, prospective study. In
      the 21-month study period, 260 unique patients were included. Tigecycline was
      given to 80 (31%) patients. The use of tigecycline during the index
      hospitalization was significantly associated with the subsequent development of
      tigecycline resistance in the same patient (OR, 6.13; 95% CI, 1.15-48.65; p
      0.03). In conclusion, the use of tigecycline with CRKP bacteriuria is common, and
      is associated with the subsequent development of tigecycline resistance. 

PMID- 24931920
TI  - Comment on Wang et al. entitled "association of tea consumption and the risk of
      oral cancer: a meta-analysis".

PMID- 24931919
TI  - Comparison of extracellular DNase- and protease-producing spoilage bacteria
      isolated from Delaware pond-sourced and retail channel catfish (Ictalurus
      punctatus).
AB  - BACKGROUND: Spoilage of fishery products begins immediately following filleting
      due to microbial growth that degrades fish tissue quality prior to consumption.
      Extensive research has been conducted to identify such bacterial populations. A
      better understanding of the mechanisms involved in fish spoilage is necessary as
      a novel remedy for microbial spoilage inhibition has yet to be established for
      fish tissue. The present study identified, for the first time, bacterial
      populations that produce extracellular DNase and protease from Delaware and local
      retail distributed channel catfish (Ictalurus punctatus) fillets. RESULTS: A
      clear trend was identified between bacteria derived from catfish filleted under
      aseptic conditions where Pseudomonas was the dominant genus. Bacteria isolated
      from retail catfish contained high quantities of DNase-producing isolates, in
      contrast to aseptic-filleted catfish tissue which had none. Both types of catfish
      sample maintained high populations of protease-producing bacterial colonies
      throughout the duration of the study. Most bacteria isolated from catfish
      intestines exhibited DNase production with no protease production. CONCLUSION:
      Specific spoilage organism populations were significantly higher on retail
      derived catfish in comparison to lab-filleted Delaware cultured catfish tissue.
      It is suggested that DNase production and protease production contribute to the
      spoilage of fish tissue as a result of mishandling and septic filleting being the
      major cause of rapid catfish tissue spoilage.

PMID- 24931921
TI  - The impact of iterative reconstruction on image quality and radiation dose in
      thoracic and abdominal CT.
AB  - PURPOSE: To compare the image quality and radiation dose between iterative
      reconstruction (IR) and standard filtered back projection (FBP) in CT of the
      chest and abdomen. MATERIALS AND METHODS: Thoracic CT was performed in 50
      patients (38 male, 12 female; mean age, 51 +/- 23 yrs; range, 7-85 yrs) and
      abdominal CT was performed in 50 patients (36 male, 14 female; mean age, 62 +/-
      13 yrs; range, 20-85 yrs), using IR as well as FBP for image reconstruction.
      Image noise was quantitatively assessed measuring standard deviation of
      Hounsfield Units (HU) in defined regions of interest in subcutaneous tissue. Scan
      length and Computed Tomography Dose Index (CTDI) were documented. Scan length,
      image noise, and CTDI of both reconstruction techniques were compared by using
      paired tests according to the nature of variables (McNemar test or Student t
      test). Overall subjective image quality and subjective image noise were compared.
      RESULTS: There was no significant difference between the protocols in terms of
      mean scan length (p>0.05). Image noise was statistically significantly higher
      with IR, although the difference was clinically insignificant (13.3 +/- 3.0 HU
      and 13.6 +/- 3.0 HU for thoracic CT and 11.5 +/- 3.1 HU and 11.7 +/- 3.0 HU for
      abdominal CT, p<0.05). There was no significant difference in overall subjective
      image quality and subjective image noise. The radiation dose was significantly
      lower with IR. Volume-weighted CTDI decreased by 64% (6.2 +/- 2.5 mGy versus 17.1
      +/- 9.5 mGy, p<0.001) for thoracic CT and by 58% (7.8 +/- 4.6 mGy versus 18.5 +/-
      8.6 mGy, p<0.001) for abdominal CT. CONCLUSIONS: Our study shows that in thoracic
      and abdominal CT with IR, there is no clinically significant impact on image
      quality, yet a significant radiation dose reduction compared to FBP.

PMID- 24931922
TI  - Can 18F-FDG PET improve the evaluation of suspicious breast lesions on MRI?
AB  - OBJECTIVE: To evaluate the impact of adding 18F-fluorine-2-deoxy-d-glucose (FDG)
      positron emission tomography (PET) in the evaluation of suspicious breast lesions
      on magnetic resonance imaging (MRI). METHODS: Sixty patients with suspicious
      breast lesions on MRI were selected to perform a PET-CT in prone position,
      dedicated to the evaluation of the breasts. The areas with increased 18F-FDG
      concentration relative to normal parenchyma were considered positive on PET-CT.
      Fusion of PET and MRI images (PET-MRI) was performed on a dedicated workstation
      to better locate corresponding lesions, and its findings were compared with
      histological results. RESULTS: 76 lesions were evaluated, including 64 mass
      lesions (84.2%) and 12 non-mass lesions (15.8%). Lesions' mean diameter on MRI
      was 29.6 +/- 19.2 mm (range 6-94 mm). PET-CT showed increased metabolically
      activity on 57 lesions (75.0%), with mean maximum SUV of 5.7 +/- 5.0 (range 0.8
      23.1). On histopathology, there were 17 (22.4%) benign and 59 (79.7%) malignant
      lesions. Considering all lesions, PET-MRI fusion provided 89.8% sensitivity,
      76.5% specificity and 86.8% accuracy. Considering only mass lesions higher than
      10mm, PET-MRI fusion provided 95.8% sensitivity, 83.3% specificity and 93.3%
      accuracy. CONCLUSION: The inclusion of 18F-FDG PET on the evaluation of
      suspicious breast lesions on MRI helped to differentiate benign from malignant
      breast lesions, especially for mass lesions with a diameter higher than 10 mm.

PMID- 24931923
TI  - Supplementation of standard pre-oxygenation with nasal prong oxygen or machine
      oxygen flush during a simulated leak scenario.
AB  - The presence of a facemask leak significantly reduces the effectiveness of pre
      oxygenation and increases the risk of post-induction hypoxia. We randomly
      assigned 24 healthy volunteers to a six-period crossover trial with and without a
      simulated facemask leak. Pre-oxygenation was performed using a standard
      anaesthesia machine circuit supplemented either by nasal prong oxygen or by
      anaesthesia machine flush oxygen. Each intervention was completed with both 3-min
      tidal breathing and 8 deep breath techniques: end-tidal oxygen fraction was used
      as the measure of pre-oxygenation effectiveness. The presence of a stimulated
      mask leak significantly reduced the effectiveness of pre-oxygenation regardless
      of the breathing method used. With a simulated facemask leak introduced, the mean
      (SD) end-tidal oxygen fraction with the 3-min tidal breath technique was 74.7
      (9.3)% compared with 57.5 (6.2%) for the 8 deep breath technique with 3-min tidal
      breathing and a leak. End-tidal oxygen fractions increased by 11.0% (95% CI 7.8
      14.3%) (p < 0.0001) with the addition of nasal prong oxygenation and 16.8% (13.6
      20.0%) (p < 0.0001) with machine oxygen flush compared with standard pre
      oxygenation. When a leak is present, 3-min tidal breathing with either nasal
      prong or anaesthesia machine flush oxygenation is an effective pre-oxygenation
      method, and preferable to the 8 deep breath method. 

PMID- 24931924
TI  - Clinical and etiological heterogeneity in patients with tracheo-esophageal
      malformations and associated anomalies.
AB  - Esophageal Atresia (EA) is a severe developmental defect of the foregut that
      presents with or without a Tracheo-Esophageal Fistula (TEF). The prevalence of
      EA/TEF over time and around the world has been relatively stable. EA/TEF is
      manifested in a broad spectrum of anomalies: in some patients it manifests as an
      isolated atresia or fistula, but in over half it affects several organ systems.
      While the associated malformations are often those of the VACTERL spectrum
      (Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal and Limb), many
      patients are affected by other malformations, such as microcephaly, micrognathia,
      pyloric stenosis, duodenal atresia, a single umbilical artery, and anomalies of
      the genitourinary, respiratory and gastrointestinal systems. Though EA/TEF is a
      genetically heterogeneous condition, recurrent genes and loci are sometimes
      affected. Tracheo-Esophageal (TE) defects are in fact a variable feature in
      several known single gene disorders and in patients with specific recurrent Copy
      Number Variations and structural chromosomal aberrations. At present, a causal
      genetic aberration can be identified in 11-12% of patients. In most, EA/TEF is a
      sporadic finding; the familial recurrence rate is low (1%). As this suggests that
      epigenetic and environmental factors also contribute to the disease, non
      syndromic EA/TEF is generally believed to be a multifactorial condition. Several
      population-based studies and case reports describe a wide range of associated
      risks, including age, diabetes, drug use, herbicides, smoking and fetal alcohol
      exposure. The phenotypical and genetic heterogeneity seen in EA/TEF patients
      indicates not one underlying cause, but several. Unraveling the complex
      multifactorial and heterogeneous etiology of EA/TEF and associated features will
      require large cohorts of patients. Combined statistical analysis of component
      findings, genome sequencing, and genome wide association studies will elucidate
      new causal genetic defects and predisposing loci in the etiology within specific
      sub-populations. Improved knowledge of environmental risk factors, genetic
      predisposition and causal genetic syndromes may improve prediction and parental
      counseling, and prevent co-morbidity. 

PMID- 24931925
TI  - Periapical status of root-filled teeth in Norwegian children and adolescents.
AB  - OBJECTIVE: To study the periapical status of root-filled permanent teeth of 9-17
      year-olds in More & Romsdal county, Norway. MATERIALS AND METHODS: All permanent
      teeth with endodontic treatment in patients born in 1994-2001 were identified in
      the dental records of the Public Dental Service. The data collected consisted of
      chart entries and radiographs. Of 1182 teeth, 174 teeth in 155 patients met
      further inclusion criteria, i.e. completed endodontic treatment and a follow-up
      with a readable radiograph of at least 1 year. Periapical status was assessed
      with the Periapical Index (PAI) and the technical quality of the root fillings
      was also quantified on a 4-grade visual scale. RESULTS: Apical periodontitis was
      found on follow-up radiographs in 25% of all teeth and in 48% of the teeth with
      pre-operative apical periodontitis. Forty-two per cent of root fillings were of
      adequate technical quality. Adequate technical quality of the root filling was
      significantly correlated with radiographic success. CONCLUSIONS: About one fourth
      of all root-filled teeth and almost half of the teeth with pre-operative apical
      periodontitis showed clear signs of the disease at recall.

PMID- 24931926
TI  - Is it safe to use a toothbrush?
AB  - AIM: To systemically collect and summarize the literature on case reports
      concerning adverse events associated with the oral use of a toothbrush. MATERIALS
      AND METHODS: Two electronic databases were searched for articles published up to
      October 2013 to identify appropriate studies using focused search terms and 'case
      reports' as a filter. Results. A comprehensive search identified 419 unique
      titles and abstracts. Ninety-four studies met the eligibility criteria. In total,
      118 subjects (age range = 1-60 years) presented adverse events related to the
      oral use of a toothbrush. Events could be summarized in five categories, of which
      ingestion was the most reported problem among the individuals (50 cases). This
      was followed by impaction of a toothbrush (27 cases). Reports more frequently
      involved females and children were more likely to have injuries compared to males
      and adults. Most of the cases that presented with adverse events of the oral use
      of a toothbrush were referred for treatment to a physician. CONCLUSIONS: The
      combined evidence related to serious adverse events as presented in case reports
      showed that the oral use of a toothbrush can be associated with ingestion,
      impaction, instant trauma, gingival traumatic injury and seizures. Given the
      incidence of reporting, important recommendations are that a toothbrush should
      not be used to induce vomiting, nor should people walk or run with this device in
      their mouths, especially children.

PMID- 24931927
TI  - Lip buccal mucosa traumatic overgrowth due to sucking habit - a 10-year follow-up
      of a non-surgical approach: a combination of behavioural and myofunctional
      therapy.
AB  - OBJECTIVE: Traumatic lesion of the lip buccal mucosa may develop due to a
      repetitive lip sucking habit, secondary to a dental space which opened in the
      dental in adult patients. The non surgical treatment approach is based on
      increasing of patient's awareness to the sucking habit along with the creation of
      a change in the oral and dental surrounding tissues. The following case included
      a failure to identify a traumatic habit of lower lip sucking, resulting in a
      buccal mucosa overgrowth. Combined conservative periodontal and orthodontic
      approach will be presented to address this clinical issue without any need for
      surgical intervention. MATERIAL AND METHODS: 56 year old female patient presented
      with a complaint of unaesthetic appearance of the intraoral right buccal mucosa
      of the lower lip at rest position due to an intensive repetitive sucking habit of
      the right lower lip segment. We initiated a non surgical treatment approach
      including increasing the patient's awareness to the sucking habit, controlling
      the periodontal disease and orthodontic treatment to align and level the dental
      arch and to close the residual space. RESULT: The soft tissue overgrowth on the
      lip buccal mucosa almost completely subsided spontaneously as a result of
      conservative dental and behavioral management without the need for any oral
      surgery intervention. A 10 years follow-up revealed no repetitive oral mucosa
      overgrowth, no spaces reopening and no sucking habit redevelopment. CONCLUSION:
      Implementation of a morphological correction will assist the patient in breaking
      the habit and creating an environment that may effectively prevent the
      reoccurrence of the habit.

PMID- 24931929
TI  - Editorial.

PMID- 24931928
TI  - Host cell pigmentation in Scenedesmus dimorphus as a beacon for nascent parasite
      infection.
AB  - Biofuels derived from the mass cultivation of algae represent an emerging
      industry that aims to partially displace petroleum based fuels. Outdoor, open
      pond, and raceway production facilities are attractive options for the mass
      culture of algae however, this mode of cultivation leaves the algae susceptible
      to epidemics from a variety of environmental challenges. Infestations can result
      in complete collapse of the algal populations and destruction of their valuable
      products making it paramount to understand the host-pathogen relationships of
      known algal pests in order to develop mitigation strategies. In the present work,
      we characterize the spatial-temporal response of photosynthetic pigments in
      Scenedesmus dimorphus to infection from Amoeboaphelidium protococcarum, a
      destructive endoparasite, with the goal of understanding the potential for early
      detection of infection via host pigment changes. We employed a hyperspectral
      confocal fluorescence microscope to quantify these changes in pigmentation with
      high spatial and spectral resolution during early parasite infection. Carotenoid
      abundance and autofluorescence increased within the first 24 h of infection while
      chlorophyll emission remained constant. Changes in host cell photosynthesis and
      bulk chlorophyll content were found to lag behind parasite replication. The
      results herein raise the possibility of using host-cell pigment changes as
      indicators of nascent parasite infection.

PMID- 24931930
TI  - Impulsive behavior in a consumer culture.
AB  - INTRODUCTION: Compulsive shopping behaviour has recently received long overdue
      attention as a clinical issue. Curiosity about this condition has led to
      questions about its identification, characterization as a disorder, and
      treatment. METHOD: This article presents two case vignettes illustrating
      diagnostic criteria and points that distinguish this disorder from OCD hoarding
      or mania. These issues are discussed. RESULTS: The authors present some suggested
      treatment approaches CONCLUSION: Greater awareness of the prevalence and social
      consequences of compulsive shopping behaviour highlights the need for treatment
      and for educational resources for clinicians and the general public. (Int J Psych
      Clin Pract 2002; 6: 65-68).

PMID- 24931931
TI  - Physical signs in psychiatry: a step towards evidence-based medicine.
AB  - INTRODUCTION: The descriptive nature of psychiatry is embedded in the traditions
      of Kraepelin, Bleuler and Freud. Diagnostic guidelines in both ICD10 and DSM-IV
      are stated to be based on the "clinical description of the variety of concepts"
      and are based on the subjective complaints, i.e. symptoms. METHOD: In particular,
      we argue that no significant effort has been made to segregate the presence of
      accompanying physical signs in Major Depressive Illness, DSM-IV 296.2x, and Panic
      Disorder Without Agoraphobia, DSM-IV 300.01. RESULT: These physical signs are
      psychophysiological correlates of clinically significant depression and anxiety.
      Advances in structural biology, genetic engineering and brain imaging provide an
      opportunity to narrow the gap between physical signs and psychiatric symptoms in
      psychiatry. CONCLUSION: Therefore we suggest that the next revisions of the DSM
      and the ICD classifications lead the way in incorporating physical signs
      alongside those symptoms pertaining to each psychiatric illness. (Int J Psych
      Clin Pract 2002; 6: 69-72).

PMID- 24931932
TI  - Risk assessment for people with mental health problems: a pilot study of
      reliability in working practice.
AB  - INTRODUCTION: This paper describes a pilot study of reliability in the risk
      assessment of people with mental health problems. Specifically, we explore the
      evidence for professional and gender bias in ratings, in addition to the general
      level of agreement between raters. METHOD: Six professional groups
      (psychiatrists, junior psychiatric doctors, nurses, community psychiatric nurses,
      social workers and occupational therapists) participated in the study and rated
      159 patients on a nine-item scale which assessed different components of risk.
      RESULTS: Contrary to some earlier work, we found no clear evidence that any one
      group consistently rated more extremely than any other group. Women were more
      cautious than men in their ratings, and this concurs with previous studies.
      Finally, a reliability study of randomly selected pairs of raters showed only
      moderate levels of agreement and, in some instances, the levels of disagreement
      were high enough to warrant concern. CONCLUSION: These findings are discussed in
      the context of current risk assessment practice and the problems associated with
      investigating reliability in naturalistic settings and designing appropriate
      rating tools for risk. (Int J Psych Clin Pract 2002; 6: 73-81).

PMID- 24931933
TI  - Clinical experience of the pharmacological treatment algorithm for major
      depression in advanced cancer patients: preliminary study.
AB  - INTRODUCTION: Treatment of major depression in advanced cancer patients is often
      difficult because of their special characteristics. METHOD: The authors developed
      a treatment algorithm for major depression in advanced cancer patients and report
      on their clinical experience using it. The applicability, tolerability, and
      clinical efficacy of the algorithm were evaluated in 95 advanced cancer patients
      with major depression. RESULTS: The algorithm was not suitable for seven patients
      and was not used correctly in 14 cases. It was correctly applied to 74 patients
      (77%), 23 of whom dropped out for cancer-related reasons (deterioration of
      physical condition, transfer to other hospitals, cancer death). As for
      tolerability, 22 patients (43%) of the 51 dropped out of the antidepressant
      treatment regimen because of delirium due to deterioration of their physical
      condition, adverse effects of the antidepressant, etc. In the 29 cases that could
      be followed up, clinical efficacy was evaluated for 4 weeks, and improvement was
      observed in 22 cases (76%). CONCLUSION: These preliminary findings suggest that
      use of the algorithm may be feasible, but that it requires some alterations to
      manage major depression in advanced cancer patients. (Int J Psych Clin Pract
      2002; 6: 83-89).

PMID- 24931934
TI  - Hamilton Depression Scale in dementia.
AB  - INTRODUCTION: Wide variations in frequency of depression in primary degenerative
      dementia (PDD) and in vascular dementia (VD) have been reported. This may perhaps
      be due to inadequacy of common diagnostic tools in detecting depression in the
      face of cognitive decline. We evaluated here the Hamilton Depression Rating Scale
      (HDRS) in demented patients with PDD and VD. METHODS: We examined 50 consecutive
      patients with PDD and 50 consecutive patients with VD. All patients underwent
      neurological examination and their depression was evaluated using DSM-III-R
      criteria and the HDRS. The data obtained were analysed for distribution of
      depression and pattern of responses obtained in the HDRS. Sensitivity,
      specificity and Youden's J-indices for different cut-off scores of the HDRS in
      its ability to detect depression in this population were calculated. RESULTS:
      Dementia was associated with depression in 38% of the patients (DSM-III-R
      criteria). HDRS scores were higher in depressed patients (z= -5.7, P < 0.0001)
      with an HDRS cut-off score of 10 being indicative of depression in demented
      patients. Symptoms related to 'affective' components of the HDRS (such as
      depressive mood and anxiety) were strongly associated with the diagnosis of
      depression (Mann-Whitney tests, P < 0.0001). CONCLUSION: Depression is frequent
      in demented patients. The HDRS has good criterion validity in the evaluation of
      depression in demented patients. (Int J Psych Clin Pract 2002; 6: 91-94).

PMID- 24931935
TI  - The impact of clozapine on electrophysiological features: how can we utilize the
      findings?
AB  - INTRODUCTION: There is a large body of findings on the impact of clozapine upon
      electrophysiological features. This study repeats several of these earlier
      studies and reports on whether, and how, these findings can be utilized in our
      particular research/clinical situation. METHODS: Neurophysiological
      investigations were carried out on 37 schizophrenia patients, before and after
      commencing a clinically indicated trial of clozapine. Data from three areas of
      investigation-EEG, quantitative EEG (QEEG), and evoked response potential (ERP)
      were compared with findings from earlier studies. Analysis was also extended to
      include clinical indicators, dosages, and several novel combinations of features.
      RESULTS: Our local population has a higher incidence of baseline abnormalities
      than that found in earlier investigations. Even with this difference, clozapine
      still leads to an increase in EEG slow-wave activity. The slow-wave increase is
      significantly correlated with an increase in P3 amplitude of the ERP. While QEEG
      changes were correlated with clinical changes, the ERP correlation did not reach
      significance levels. CONCLUSIONS: Electrophysiological findings, particularly
      from small numbers of studies, may not be generalizable to all populations.
      Findings which were replicated, however, support the potential use of slow wave
      changes in the EEG in clinical management. (Int J Psych Clin Pract 2002; 6: 95
      102).

PMID- 24931936
TI  - What have you been told about your illness? Information about diagnosis among
      psychiatric inpatients.
AB  - INTRODUCTION: In current psychiatric practice clinicians tend to share with
      patients information regarding their illness. However, little is known about what
      the patients would in fact like to know about their diagnosis and prognosis.
      METHOD: We have conducted a cross-sectional survey among psychiatric inpatients,
      to explore what they believe is wrong with them, what they have been told and by
      whom, and what they wish to know about their illness. RESULTS: The results have
      shown that 80% of the patients received some information about their illness and
      37% of the participants had satisfactory insight. However only 46% of the
      participants declared that they wished to know what was wrong with them.
      CONCLUSIONS: We conclude that although many patients would like to know the
      truth, the rights of those who do not wish to know should also be respected.
      Therefore the diagnosis of mental disorder should not be routinely disclosed, but
      mental health professionals should take into consideration their patients'
      preferences and act appropriately to their choice. (Int J Psych Clin Pract 2002;
      6: 103-106).

PMID- 24931938
TI  - Risperidone for the treatment of delusional disorder.
AB  - INTRODUCTION: The overlap between diagnostic criteria for schizophrenia and
      delusional disorder (DD) may cause diagnostic confusion. This is important if
      response to treatment differs. Risperidone, an atypical antipsychotic, is
      established in the treatment of schizophrenia, although less so in other
      psychotic conditions. METHOD: We report the case of a woman who developed DD,
      persecutory type, at the age of 50 years. Treatment with sulpiride 200-800 mg
      daily caused side-effects of drowsiness and 'hangover' and, consequently, non
      compliance. Written informed consent was gained for a 24-week, randomized, double
      blind, placebo-controlled, crossover trial of risperidone, initiated at 1 mg
      daily and increasing to 2 mg daily. RESULTS: Significant improvement was found,
      as assessed by the Brief Psychiatric Rating Scale, Positive and Negative Symptom
      Schedule and Maudsley Assessment of Delusions Schedule. CONCLUSION: We believe
      that this is the first case study reporting the resolution of persecutory DD with
      risperidone. A controlled clinical trial of risperidone in the treatment of
      patients with DD is warranted. (Int J Psych Clin Pract 2002; 6: 113-116).

PMID- 24931937
TI  - Is olanzapine better than haloperidol in resistant schizophrenia? A double-blind
      study in partial responders.
AB  - INTRODUCTION: To compare the efficacy and safety of olanzapine and haloperidol in
      partial-responder paranoid schizophrenic patients. METHOD: In this multi-centre,
      double-blind study, 28 patients with DSM-IV paranoid schizophrenia were
      randomized to receive 14 weeks treatment with either olanzapine or haloperidol at
      flexible doses. The pre- and post-treatment assessment included the Brief
      Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative
      Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes
      Akathisia Rating Scale. RESULTS: The two treatment groups showed similar
      improvement on the BPRS positive symptoms subscale, while the improvement of BPRS
      negative symptoms subscale was significant only in the olanzapine group (ANOVA
      with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine
      treated patients experienced a significant improvement of negative symptoms as
      rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016).
      No significant differences were found between the two groups on the Simpson and
      Angus Rating Scale scores, but a significant difference was found in the Barnes
      Akathisia Rating Scale scores: no patient in the olanzapine-treated group
      experienced akathisia, while a few patients in the haloperidol-treated group
      showed this side-effect, thus resulting in a significant group effect detected by
      the ANOVA (F=4.23, P =0.05). CONCLUSIONS: These preliminary results suggest that
      olanzapine is superior to haloperidol in the treatment of partial-responder
      paranoid schizophrenic patients, and also shows a better tolerability profile.
      Further investigations, including different diagnostic subgroups, are still
      needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin
      Pract 2002; 6: 107-111).

PMID- 24931939
TI  - "The detergent is circulating in my blood": a case report.
AB  - INTRODUCTION: We report an interesting case of monosymptomatic hypochondriacal
      psychosis (MHP) which, because of its rarity, tends to be neglected in
      differential diagnosis. The patient presented with delusions including smelling
      the odour of detergent and thinking detergent was circulating in his blood. He
      had many medical and paramedical treatments over 21/2 years, and was finally
      diagnosed with MHP. METHOD: Risperidone was then started, and gradually
      increased. RESULTS: A significant improvement was observed. However, risperidone
      was discontinued, because of its hypomanic effects. CONCLUSION: We suggest that
      risperidone may be an effective alternative treatment in MHP cases, but the
      hypomanic effects may limit its usefulness. (Int J Psych Clin Pract 2002; 6: 117
      119).

PMID- 24931940
TI  - Safety and efficacy of long-term low-dose clozapine aftercare treatment in a
      patient with learning difficulties who suffered from neuroleptic malignant
      syndrome.
AB  - INTRODUCTION: Antipsychotic medication continues to be an essential component in
      the treatment of schizophrenia. Neuroleptic malignant syndrome (NMS) is one of
      the most serious complications of neuroleptic treatment and the optimal
      therapeutic aftercare regimen for patients is unclear. Also, it is not clear if
      low-dose neuroleptic maintenance in such patients is safe and efficient enough
      over time. METHOD: We present a case of a 56-year-old woman suffering from
      schizoaffective disorder, who was successfully treated with a low dosage of
      clozapine for 6.5 years following a NMS episode. RESULT: To the best of our
      knowledge this is the first report of such a long-term beneficial use of low-dose
      clozapine in a patient who previously underwent such a serious complication.
      CONCLUSION: Large-scale studies are needed to substantiate this observation. (Int
      J Psych Clin Pract 2002; 6: 121-123).

PMID- 24931942
TI  - 50 years of research on the effect of physician communication behavior on health
      outcomes.

PMID- 24931943
TI  - Role of cell-cell adhesion complexes in embryonic stem cell biology.
AB  - Pluripotent embryonic stem cells (ESCs) can self-renew or differentiate into any
      cell type within an organism. Here, we focus on the roles of cadherins and
      catenins - their cytoplasmic scaffold proteins - in the fate, maintenance and
      differentiation of mammalian ESCs. E-cadherin is a master stem cell regulator
      that is required for both mouse ESC (mESC) maintenance and differentiation. E
      cadherin interacts with key components of the naive stemness pathway and ablating
      it prevents stem cells from forming well-differentiated teratomas or contributing
      to chimeric animals. In addition, depleting E-cadherin converts naive mouse ESCs
      into primed epiblast-like stem cells (EpiSCs). In line with this, a mesenchymal
      to-epithelial transition (MET) occurs during reprogramming of somatic cells
      towards induced pluripotent stem cells (iPSCs), leading to downregulation of N
      cadherin and acquisition of high E-cadherin levels. beta-catenin exerts a dual
      function; it acts in cadherin-based adhesion and in WNT signaling and, although
      WNT signaling is important for stemness, the adhesive function of beta-catenin
      might be crucial for maintaining the naive state of stem cells. In addition,
      evidence is rising that other junctional proteins are also important in ESC
      biology. Thus, precisely regulated levels and activities of several junctional
      proteins, in particular E-cadherin, safeguard naive pluripotency and are a
      prerequisite for complete somatic cell reprogramming. 

PMID- 24931944
TI  - CrossTalk proposal: Weighing the evidence for Class A GPCR dimers, the evidence
      favours dimers.

PMID- 24931945
TI  - CrossTalk opposing view: Weighing the evidence for class A GPCR dimers, the jury
      is still out.

PMID- 24931946
TI  - Rebuttal from Michel Bouvier and Terence E. Hebert.

PMID- 24931947
TI  - Rebuttal from Nevin A. Lambert and Jonathan A. Javitch.

PMID- 24931948
TI  - Taking vascular health to new heights: the short- and long-term impacts of
      altitude on cardiovascular function.

PMID- 24931949
TI  - High prevalence of metabolic syndrome and of insulin resistance in psoriatic
      arthritis is associated with the severity of underlying disease.
AB  - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MetS) and of
      insulin resistance (IR) in an ethnically homogeneous cohort of established
      psoriatic arthritis (PsA), and to identify clinical associations of MetS and IR
      in patients with PsA. METHODS: A cohort of 283 patients with PsA all meeting
      ClASsification for Psoriatic ARthritis (CASPAR) criteria was included. All
      underwent detailed skin and rheumatologic assessments, along with cardiovascular
      risk factor evaluation. IR was defined as an elevated homeostasis model
      assessment (HOMA-IR) value of > 2.5. Severe PsA was defined as the presence of 1
      or more of the PsA-related radiographic damage features (peripheral joint
      erosions, osteolysis, sacroiliitis), and PsA requiring tumor necrosis factor
      inhibitor therapy. RESULTS: The demographic and clinical characteristics of the
      cohort were mean age 54.6 +/- 12 years, 52% female, mean PsA duration 19 +/- 9
      years. MetS was present in 44% of the studied patients (n = 283). On multiple
      regression analysis, a significant association of MetS was noted with more severe
      PsA (OR 4.47, p < 0.001), higher smoking pack-years (OR 1.03, p = 0.02), and
      worse EQ-5D scores (OR 1.28, p = 0.02). Data on IR were available for 263
      patients, and among them, the mean HOMA-IR was 1.43 +/- 1.09. Forty-one patients
      (16%) had IR. On multiple regression analysis, a significant association of IR
      was noted with more severe PsA (OR 3.49, p = 0.03), later psoriasis age of onset
      (OR 1.07, p = 0.001), and higher body mass index (OR 1.22, p < 0.001).
      CONCLUSION: Among patients with PsA, MetS and IR are highly prevalent, and are
      independently associated with the severity of underlying PsA.

PMID- 24931951
TI  - Clinical and serological predictors of remission in rheumatoid arthritis are
      dependent on treatment regimen.
AB  - OBJECTIVE: Early intensive treatment is now the cornerstone for the management of
      rheumatoid arthritis (RA). In the era of personalized medicine, when treatment is
      becoming more individualized, it is unclear from the current literature whether
      all patients with RA benefit equally from such intensive therapies. We
      investigated the benefit of different treatment regimens on remission rates when
      stratified to clinical and serological factors. METHODS: The Combination Anti
      rheumatic Drugs in Early Rheumatoid Arthritis (CARDERA) trial recruited patients
      with RA of less than 2 years' duration who had active disease. The trial compared
      4 treatment regimens: methotrexate monotherapy, 2 different double therapy
      regimens (methotrexate and cyclosporine or methotrexate and prednisolone) and 3
      drug therapy. Clinical predictors included age, male sex, and tender joint count
      (TJC) and serological biomarkers included rheumatoid factor (RF) and
      anticitrullinated protein antibodies (ACPA). RESULTS: Patients who were male,
      over 50 years, had >= 6 TJC, were RF-IgM-positive, or ACPA-positive were more
      likely to achieve remission at 24 months using 3-drug therapy compared to
      monotherapy (OR 2.99, 4.95, 2.71, 2.54, and 3.52, respectively). There were no
      differences in response to monotherapy and 3-drug therapy if patients were
      female, under 50 years, had < 6 TJC, or were seronegative. CONCLUSION: Early
      intensive regimens have become the gold standard in the treatment of early RA.
      Our study suggests that this intensive approach is only superior to monotherapy
      in certain subsets of patients. Although these are unlikely to be the only
      predictors of treatment response, our study brings us a step closer to achieving
      personalized medicine in RA.

PMID- 24931950
TI  - Ischemic digital ulcers affect hand disability and pain in systemic sclerosis.
AB  - OBJECTIVE: Ischemic digital ulcers (DU) are frequent and severe complications of
      systemic sclerosis (SSc). The purpose of our study was to assess the effect of DU
      on hand disability and pain in patients with SSc. METHODS: The Evaluation of the
      Impact of Recurrent Ischemic DU on Hand Disability in Patients with SSc (ECLIPSE)
      is a prospective, multicenter, noninterventional study with a 2-year followup.
      Patients with SSc who experienced at least 1 DU in the previous year and received
      bosentan therapy were included between October 2009 and March 2011. This cohort
      is described at the time of inclusion. RESULTS: There were 190 patients (132
      females) from 53 centers. Mean age +/- SD was 43 +/- 15 years at SSc diagnosis
      and 53 +/- 15 years at inclusion. In 105 patients (56.2%), DU were the first non
      Raynaud symptoms of SSc. The mean time interval between the occurrence of Raynaud
      phenomenon and the first DU episode was 6.6 +/- 9.1 years. The mean numbers of
      active DU and fingers affected per patient for both hands were 2.3 +/- 1.8 and
      2.2 +/- 1.6, respectively. Presence of active DU at inclusion was significantly
      associated with pain and impaired hand function: Visual Analog Scale for pain (0
      to 10) was 6.2 +/- 2.6 versus 2.5 +/- 2.4 (p < 0.0001) and Cochin Hand Function
      Scale for hand disability (0 to 90) was 38 +/- 20 versus 25 +/- 19 (p < 0.0001),
      respectively. CONCLUSION: DU represent a major sign of SSc, often affecting
      multiple fingers and both hands. They are significantly associated with pain and
      hand disability.

PMID- 24931952
TI  - English language proficiency, health literacy, and trust in physician are
      associated with shared decision making in rheumatoid arthritis.
AB  - OBJECTIVE: Treat-to-target guidelines promote shared decision making (SDM) in
      rheumatoid arthritis (RA). Also, because of high cost and potential toxicity of
      therapies, SDM is central to patient safety. Our objective was to examine
      patterns of perceived communication around decision making in 2 cohorts of adults
      with RA. METHODS: Data were derived from patients enrolled in 1 of 2
      longitudinal, observational cohorts [University of California, San Francisco
      (UCSF) RA Cohort and RA Panel Cohort]. Subjects completed a telephone interview
      in their preferred language that included a measure of patient-provider
      communication, including items about decision making. Measures of trust in
      physician, education, and language proficiency were also asked. Logistic
      regression was performed to identify correlates of suboptimal SDM communication.
      Analyses were performed on each sample separately. RESULTS: Of 509 patients
      across 2 cohorts, 30% and 32% reported suboptimal SDM communication. Low trust in
      physician was independently associated with suboptimal SDM communication in both
      cohorts. Older age and limited English proficiency were independently associated
      with suboptimal SDM in the UCSF RA Cohort, as was limited health literacy in the
      RA Panel Cohort. CONCLUSION: This study of over 500 adults with RA from 2
      demographically distinct cohorts found that nearly one-third of subjects report
      suboptimal SDM communication with their clinicians, regardless of cohort. Lower
      trust in physician was independently associated with suboptimal SDM communication
      in both cohorts, as was limited English language proficiency and older age in the
      UCSF RA Cohort and limited health literacy in the RA Panel Cohort. These findings
      underscore the need to examine the influence of SDM on health outcomes in RA.

PMID- 24931953
TI  - Behcet syndrome manifestations and activity in the United States versus Turkey --
      a cross-sectional cohort comparison.
AB  - OBJECTIVE: To compare clinical manifestations and activity of Behcet syndrome
      (BS) in the United States versus Turkey using validated outcome measures.
      METHODS: Consecutive patients with BS from the US National Institutes of Health
      (NIH), New York University, and the University of Istanbul were evaluated.
      Disease activity was measured using the Behcet's Syndrome Activity Scale (BSAS)
      and the Behcet's Disease Current Activity Form (BDCAF) with quality of life
      measured by the Behcet Disease Quality of Life (BDQOL) form. One-way ANOVA, t
      tests, and multivariate regression analyses were performed. RESULTS: Mean age did
      not differ between sites; however, more women were seen in the United States
      versus in Turkey (p < 0.001), and disease duration was longer in the United
      States (p = 0.02). Organ manifestations were similar for oral and genital ulcers,
      skin disease, arthralgia, eye disease, and thrombosis. However, more
      gastrointestinal (p < 0.001) and neurologic disease (p = 0.003) was seen in the
      United States. BSAS and BDCAF scores were worse in the United States compared to
      Turkey (p = 0.013 and < 0.001, respectively). Worse mean BDQOL scores were
      observed at the NIH compared to Istanbul (not significant). Multivariable
      regression models showed worse scores in ethnically atypical patients for BSAS
      and BDCAF (p = 0.04 and p = 0.001), American patients for BDCAF (p = 0.01), older
      age for BDCAF (p = 0.005), and women for BDQOL (p = 0.01). CONCLUSION:
      Demographic and clinical manifestations of BS differ between sites with higher
      disease activity in the United States compared to Turkey. Referral patterns, age,
      sex, ethnicity, and country of origin may be important in these differences.
      These observations raise the question of whether pathogenic mechanisms differ in
      Turkish and American patients.

PMID- 24931954
TI  - The association of socioeconomic status and symptom severity in persons with
      fibromyalgia.
AB  - OBJECTIVE: Although persons with lower socioeconomic status (SES) generally have
      poorer health status for many medical conditions, the association of SES with
      symptom severity in fibromyalgia (FM) is unknown. The subjective symptoms of FM
      may be influenced by personal perceptions, and environmental and psychosocial
      factors. Therefore SES may influence symptom expression and severity. METHODS:
      Data for this cross-sectional analysis were obtained from a real-life prospective
      cohort of 246 patients with FM categorized according to level of education: high
      school graduates or less (Group 1; n = 99), college graduates (Group 2; n = 84),
      and university graduates (Group 3; n = 63). The association between level of
      education, a well-validated measure of SES, and disease severity, functional
      status, and quality of life were examined. RESULTS: Lower education was
      significantly associated with older age (p = 0.039), current unemployment (p <
      0.001), and more severe disease, as measured by patient global assessment disease
      activity (p = 0.019), McGill Pain Questionnaire (p = 0.026), Pain Disability
      Index (p = 0.031), Pain Catastrophizing Scale (p = 0.015), Health Assessment
      Questionnaire (p = 0.001), and Fibromyalgia Impact Questionnaire (p = 0.002), but
      not pain level, anxiety, or depression. These associations remained significant
      even upon adjusting for age and sex differences. CONCLUSION: Patients with FM and
      lower SES, as assessed by education level, reported greater symptom severity and
      functional impairment, despite reporting similar levels of pain, depression, and
      anxiety. Although FM spans all socioeconomic groups, factors other than specific
      disease characteristics or mental status, appear to play an important role in
      patients' perception of illness.

PMID- 24931955
TI  - Autoantibodies to the Rpp25 component of the Th/To complex are the most common
      antibodies in patients with systemic sclerosis without antibodies detectable by
      widely available commercial tests.
AB  - OBJECTIVE: Antinuclear antibodies (ANA) occur in up to 95% of patients with
      systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e.,
      centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP).
      Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the
      Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA
      positivity in patients with SSc remains unknown. METHODS: Sera from 873 patients
      with SSc were tested for ANA, and SSc-associated antibodies were measured.
      Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA
      ), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins
      and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA)
      and Rpp25 ELISA. RESULTS: Anti-Th/To antibodies occurred in 19/53 (36%), as
      determined by IP, and were the most common autoantibody in ANA+/ENA- SSc. Of
      those samples, 50/53 were available for additional testing by CLIA and ELISA.
      Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50
      patients. Receiver-operating characteristic curve analysis showed similar
      discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31)
      by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive
      percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4
      83.7%) or 10/19 (52.6%, 95% CI 73.3-94.2%), respectively. Negative percent
      agreement was 100% for both assays. CONCLUSION: Autoantibodies to the Th/To
      autoantigen are important in patients with SSc who have been considered negative
      for SSc-specific or SSc-associated antibodies by widely available commercial
      assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays
      detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.

PMID- 24931956
TI  - Immediate efficacy of neuromuscular exercise in patients with severe
      osteoarthritis of the hip or knee: a secondary analysis from a randomized
      controlled trial.
AB  - OBJECTIVE: Knowledge about the effects of exercise in severe and endstage
      osteoarthritis (OA) is limited. The aim was to evaluate the efficacy of a
      neuromuscular exercise program in patients with clinically severe hip or knee OA.
      METHODS: This was a randomized controlled assessor-blinded trial. Patients
      received an educational package (care-as-usual) only, or care-as-usual plus an 8
      week neuromuscular exercise intervention (NEMEX-TJR). NEMEX-TJR was supervised by
      a physiotherapist, twice weekly for 1 h. The primary outcome was Activities of
      Daily Living (ADL) subscale from the Hip disability and Osteoarthritis Outcome
      Score (HOOS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS)
      questionnaire. The secondary outcomes were the HOOS/KOOS subscales Pain,
      Symptoms, Sport and Recreation, and Joint-related Quality of Life. Exploratory
      outcomes were functional performance measures and lower limb muscle power.
      RESULTS: Included were 165 patients, 56% female, average age 67 years (SD +/- 8),
      and a body mass index of 30 (SD +/- 5), who were scheduled for primary hip or
      knee replacement. The postintervention difference between mean changes in ADL was
      7.2 points (95% CI 3.5 to 10.9, p = 0.0002) in favor of NEMEX-TJR compared with
      control. Second, there were statistically significant differences between groups
      in favor of NEMEX-TJR on all self-reported outcomes and most functional
      performance tests (walk, chair stands, and 1-leg knee bends). Stratified analyses
      according to joint revealed moderate effect size for ADL for hip patients (0.63,
      95% CI 0.26 to 1.00). Corresponding effect size for knee patients was small (0.23
      95% CI -0.14 to 0.60). CONCLUSION: Feasibility of neuromuscular exercise was
      confirmed in patients about to have total joint replacement. Self-reported
      activities of daily living and objective performance were improved and pain
      reduced immediately following 8 weeks of neuromuscular exercise. While the
      effects were moderate in hip OA, they were only small in knee OA.
      ClinicalTrials.gov Identifier: NCT01003756.

PMID- 24931957
TI  - Female sex and oligoarthritis category are not risk factors for uveitis in
      Italian children with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the risk factors for chronic anterior uveitis in
      patients with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts
      of patients followed between January 1987 and December 2011 were reviewed to
      establish whether they had uveitis. Inclusion criteria were a diagnosis of JIA
      and a disease category of persistent oligoarthritis, extended oligoarthritis,
      rheumatoid factor-negative polyarthritis, psoriatic arthritis, or
      undifferentiated arthritis. Risk factors included sex, age at arthritis onset,
      disease category, and antinuclear antibody (ANA) status. The association of risk
      factors with occurrence of uveitis was evaluated by survival analysis, with first
      episode of uveitis as the event of interest, and Cox regression analysis.
      RESULTS: Of a total of 1189 patients, 278 (23.4%) had uveitis a median of 1.1
      years after onset of arthritis. There was no difference in the cumulative
      probability of developing uveitis between males and females and between patients
      belonging to different JIA categories, whereas uveitis was strongly associated
      with age at arthritis onset <= 3.5 years and positive ANA. Patients possessing
      the latter 2 factors in combination had a greater probability of having uveitis
      than patients who had either of them alone. CONCLUSION: In our patients, the risk
      of uveitis was related to younger age at onset of arthritis and presence of ANA,
      but not to female sex and disease category. This finding suggests that the
      patients who require the most intensive ophthalmologic screening are those who
      have early-onset JIA and are ANA-positive, regardless of their sex or disease
      subtype.

PMID- 24931958
TI  - Analysis of the effect of the oral contraceptive pill on clinical outcomes in
      women with ankylosing spondylitis.
AB  - OBJECTIVE: There are unexplained sex-specific changes in the clinical expression
      of ankylosing spondylitis (AS). We sought to examine the potential effect of
      exogenous estrogen in the form of oral contraceptive pills (OCP) on AS initiation
      and severity. METHODS: This cross-sectional study consisted of women with AS from
      the membership of the Spondylitis Association of America. Measures of disease
      severity included use of biological agents and hip replacement surgery, while
      Bath AS Functional Index (BASFI) scores served as a surrogate marker of
      disability. Information was obtained using a patient questionnaire on patient
      demographics, OCP use, pregnancy history, AS duration, medication use, and hip
      replacement. RESULTS: There were 571 women with AS who participated in our study,
      consisting of 448 OCP ever-users and 123 non-OCP users. The mean age of OCP users
      was 42.7 yrs (+/- 11.5) and of non-OCP users, 48.4 yrs (+/- 12.1). No difference
      was noted in the age at initial onset of back pain. However, OCP users were
      significantly younger at the time of diagnosis of AS (36.5 yrs vs 39.1 yrs, p =
      0.02). There were no significant differences between the 2 groups in tumor
      necrosis factor inhibitor or opioid use, BASFI scores, pregnancy complications,
      or hip surgery. CONCLUSION: The use of exogenous estrogens in the form of OCP is
      not associated with a measurable effect on initiation or severity of AS. Biologic
      and social factors may contribute to earlier diagnosis of AS in OCP users. This
      is the largest study to date investigating the potential effect of exogenous
      estrogens in women with AS.

PMID- 24931960
TI  - Biomarkers of bone metabolism in ankylosing spondylitis in relation to
      osteoproliferation and osteoporosis.
AB  - OBJECTIVE: To identify biomarkers for bone metabolism in patients with ankylosing
      spondylitis (AS) and to determine the relationship between these biomarkers and
      disease activity, back mobility, osteoproliferation, and bone mineral density
      (BMD). METHODS: Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1),
      sclerostin, soluble receptor activator of nuclear factor-kappaB ligand (sRANKL),
      and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease
      Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity
      Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein
      (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis
      Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine
      radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured
      with dual-energy x-ray absorptiometry. RESULTS: Two hundred four patients with AS
      (NY criteria; 57% men), with a mean age of 50 +/- 13 years and disease duration
      15 +/- 11 years, and 80 age and sex-matched controls were included. The patients
      with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower
      levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the
      controls. High CRP was associated with low sclerostin (r(S) = -0.21, p = 0.003)
      and DKK-1 (r(S) = -0.14, p = 0.045). In multiple linear regression analyses,
      increasing BASMI and mSASSS were independently associated with older age, male
      sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained
      associated with a high number of smoking pack-years after adjusting for age. Low
      BMD of femoral neck was associated with high mSASSS after adjusting for age.
      CONCLUSION: Serum levels of Wnt-3a are elevated in AS and associated with
      increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a
      biomarker for the osteoproliferative process.

PMID- 24931959
TI  - The diagnostic performance of anterior knee pain and activity-related pain in
      identifying knees with structural damage in the patellofemoral joint: the
      Multicenter Osteoarthritis Study.
AB  - OBJECTIVE: To determine the diagnostic test performance of location of pain and
      activity-related pain in identifying knees with patellofemoral joint (PFJ)
      structural damage. METHODS: The Multicenter Osteoarthritis Study is a US National
      Institutes of Health-funded cohort study of older adults with or at risk of knee
      osteoarthritis. Subjects identified painful areas around the knee on a knee pain
      map and the Western Ontario and McMaster Universities Osteoarthritis Index was
      used to assess pain with stairs and walking on level ground. Cartilage damage and
      bone marrow lesions were assessed from knee magnetic resonance imaging. We
      determined the sensitivity, specificity, positive and negative predictive values
      for presence of anterior knee pain (AKP), pain with stairs, absence of pain while
      walking on level ground, and combinations of tests in discriminating knees with
      isolated PFJ structural damage from those with isolated tibiofemoral joint (TFJ)
      or no structural damage. Knees with mixed PFJ/TFJ damage were removed from our
      analyses because of the inability to determine which compartment was causing
      pain. RESULTS: There were 407 knees that met our inclusion criteria. "Any" AKP
      had a sensitivity of 60% and specificity of 53%; and if AKP was the only area of
      pain, the sensitivity dropped to 27% but specificity rose to 81%. Absence of
      moderate pain with walking on level ground had the greatest sensitivity (93%) but
      poor specificity (13%). The combination of "isolated" AKP and moderate pain with
      stairs had poor sensitivity (9%) but the greatest specificity (97%) of strategies
      tested. CONCLUSION: Commonly used questions purported to identify knees with PFJ
      structural damage do not identify this condition with great accuracy.

PMID- 24931961
TI  - Association of leptin receptor gene polymorphisms with growth and feed efficiency
      in meat-type chickens.
AB  - Many genetic factors influence the growth and feed intake of birds. In the
      current study, we evaluated the association of 8 previously reported SNP in the
      chicken leptin receptor (LEPR) gene with BW, BW gain (BWG), feed intake (FI), and
      feed conversion ratio (FCR). Four SNP with a very low minor allele frequency were
      removed by genotype quality control. The experimental population consisted of 796
      pedigreed males from 2 genetically unrelated yellow meat-type chicken strains,
      335 chickens from N202, and 461 chickens from N301. The BW at 49 (BW49) and 70 d
      of age (BW70) and FI (from 49 to 70 d of age) were measured individually. The BWG
      and FCR were calculated based on BW and FI in the interval between 49 to 70 d.
      The results indicated that rs14657336, rs13684613, rs13684615, and rs13684616
      were found in strong linkage disequilibrium. This linkage disequilibrium block
      was significantly associated with BW49 (P < 0.05), BW70 (P < 0.05), and FI (P <
      0.05) in the N202 strain, and FCR (P < 0.01) in the N301 strain, respectively. In
      addition, the GTACGTAC diplotype had the highest BWG and FI in both strains. The
      association revealed in this study suggests the need for further functional study
      on the role of LEPR gene in regulating feed intake and FCR of chickens. 

PMID- 24931962
TI  - Separation of digesta fractions complicates estimation of ileal digestibility
      using marker methods with Cr2O3 and cobalt-ethylenediamine tetraacetic acid in
      broiler chickens.
AB  - Marker methodologies to measure ileal and total tract digestibilities of diets
      varying in content and degradability of dietary fiber in broiler chickens were
      evaluated. Chromium sesquioxide (Cr2O3) and cobalt-ethylenediamine tetraacetic
      acid (Co-EDTA) were used as markers of solid and soluble fractions, respectively,
      and compared with digestibility values obtained with the total collection method.
      Groups of broilers (n = 17, 11 broilers/group) were assigned to a low-fiber diet
      or 1 of 2 high-fiber diets, the latter 2 containing 35% rapeseed meal (RSM).
      Pectolytic enzymes were added to one RSM diet to improve degradability of the
      fiber fraction. Excreta were quantitatively collected for 96 h, and contents from
      ileum and ceca were collected at slaughter at 29, 30, or 31 d of age. Chromium
      recovery in excreta ranged between 86 and 95%, whereas cobalt recovery was
      considerably lower (66 to 70%). Chromium:cobalt ratio was higher in ileal digesta
      than in feed. Hardly any chromium was found in the ceca, indicating that
      separation of the marker and specific digesta fractions occurs. Estimates of
      apparent total tract digestibility (ATTD) were lower when calculated using the
      marker method compared with the total collection method, particularly in high
      fiber diets. Using Cr2O3 as a marker, differences were relatively small and
      effects due to enzyme addition were generally similar. Using Co-EDTA as a marker,
      ATTD of all components were lower compared with values obtained using the
      collection method (3 to 45 percentage units, P < 0.001), likely related to the
      low Co recovery. When estimating apparent ileal digestibility (AID), separation
      of marker and digesta resulted in unrealistically high estimates for the
      digestibility of nonglucose polysaccharides (54 to 66%), exceeding ATTD values by
      16 to 42 percentage units. Moreover, the effect of pectolytic enzyme addition on
      the AID of nonglucose polysaccharides was in the opposite direction when compared
      with total collection. The data illustrate that fractionation of digesta,
      particularly in high-fiber diets, complicates accurate AID measurements in
      broilers, regardless of the choice of markers used. 

PMID- 24931963
TI  - Growth performance, meat quality traits, and genetic mapping of quantitative
      trait loci in 3 generations of Japanese quail populations (Coturnix japonica).
AB  - The current research was conducted to compare growth, carcass traits, pH,
      intramuscular collagen (IMC) properties, and genetic bases of IMC and carcasses
      (breast-muscle weight) of different lines and generations of adult males and
      females of Japanese quail (Coturnix japonica). Forty-four quails (generation F0),
      22 Pharaoh (F-33) meat-type males and 22 Standard (S-22) laying-type females,
      were crossed to produce the F1 hybrids generation. The F2 generation was created
      by mating one F1 male with one F1 female, full siblings. The birds, randomly
      chosen from F0 (22 males and 22 females), F1 (22 males and 22 females), and F2
      (84 males and 152 females) were raised to 20 wk of age in collective cages.
      Quails were fed ad libitum commercial diets. At slaughter, all birds were
      individually weighed (after a fasting period of 12 h) and dressing yield (without
      giblets) was calculated. The carcasses were then dissected. Genomic DNA was
      extracted from all of the blood, and 30 microsatellite markers located on 2 quail
      chromosomes were genotyped. The F -: 33 quails had higher in vivo and postmortem
      performances and a higher abdominal fat percentage than those of the egg line.
      Meat from S -: 22 quails had a slower collagen maturation
      (hydroxylysylpyridinoline crosslink/collagen) and a higher ultimate pH. The F1
      and F2 generations showed an evident sexual dimorphism, and an additional effect
      could be due to hybrid heterosis evident in F2. Meat from quails of F1 and F2
      generations had a lower IMC amount with a higher degree of collagen maturation
      compared with parental lines. Two statistically significant QTL have been
      detected on quail chromosome 2 (CJA02): a QTL with an additive effect (0.50) for
      IMC in the marker bracket GUJ0037 and GUJ0093; a second QTL with additive (1.32)
      and dominant (1.91) effects for breast-muscle weight in the marker bracket
      GUJ0084 and GUJ0073. To our knowledge, this is the first report of a QTL
      associated with breast-muscle weight and IMC in quail and poultry species,
      respectively. 

PMID- 24931964
TI  - Recovery of Salmonella serovar Enteritidis from inoculated broiler hatching eggs
      using shell rinse and shell crush sampling methods.
AB  - This study compared the recovery of Salmonella from hatching eggs using 3
      sampling methods (eggshell rinsing, eggshell crush following a previous rinse,
      and eggshell crush without previous rinse). Eggshells were drop-inoculated with
      approximately 10(1), 10(2), or 10(3) cfu/eggshell of Salmonella Enteritidis and
      allowed to dry at room temperature for 1 or 24 h. For the shell rinse groups,
      each inoculated egg was rinsed with buffered peptone water. These rinsed eggs
      were used for the shell crush with previous rinse groups, and each egg was
      aseptically cracked, the contents discarded, and the eggshell and membranes
      crushed with buffered peptone water. This same crush procedure was used for the
      shell crush without previous shell rinse eggs. The recovery of Salmonella 1 h
      after inoculation for shell rinse sampled eggs was 16% positive at 10(1), 49% at
      10(2), and 93% at 10(3) cfu/eggshell challenge. For the shell crush with previous
      shell rinse, sampled egg recovery was 0% positive at 10(1), 3% at 10(2), and 17%
      at 10(3) cfu/eggshell. For the shell crush, sampled eggs had recovery of 23%
      positive at 10(1), 69% at 10(2), and 96% at 10(3) cfu/eggshell challenge. The
      recovery of Salmonella 24 h after inoculation for the shell rinse eggs was 3%
      positive at 10(1), 12% at 10(2), and 22% at 10(3) cfu/eggshell challenge;
      recovery for shell crush with previous shell rinse sampling was 2% positive at
      10(1), 8% at 10(2), and 5% at 10(3) cfu/eggshell challenge; and for the shell
      crush sampling recovery was 2% at 10(1), 32% at 10(2), and 42% at 10(3)
      cfu/eggshell challenge. Eggshell crush was a more sensitive (~10 percentage
      points) sampling method than eggshell rinse at both 1 and 24 h, but both methods
      were equally optimal when the inoculum was at 10(3) and samples were collected
      after 1 h. Waiting 24 h after inoculation to sample significantly lowered the
      recovery for both the shell rinse and shell crush sampling methods by ~40
      percentage points.

PMID- 24931965
TI  - Production characteristics of Hy-Line W36 laying hens hatched from white and
      tinted eggs.
AB  - Eggshell color can greatly influence visual appeal of table eggs, and within the
      United States, table eggs are normally sorted and marked according to eggshell
      color to maximize consumer appeal. Recently, table egg producers have noted
      increased incidence of "off-color" or tinted (TT) eggs derived from white egg
      laying breeder hens. Therefore, the objectives of this study were to determine
      the production characteristics and resultant eggshell color of laying hens
      hatched from different colored eggs. Hy-Line W36 eggs were obtained from a
      commercial breeder operation and eggshell color was assessed with a colorimeter
      to separate eggs into groups of tinted (TT) and nontinted (NT) eggs before
      incubation. Treatment groups were placed into separate hatching trays. At
      hatching, chicks from each treatment group were individually wing-banded. Pullets
      were randomly allocated into cages according to treatment groups at 18 wk. Birds
      were placed into individual cages, with 5 consecutive cages representing a
      treatment replicate. Each treatment was replicated 24 times for a total of 120
      birds per treatment and fed a nutritionally complete layer diet. Production
      performance was evaluated from 18 to 34 wk of age. Average weekly egg production
      was calculated. Feed intake, egg weights, egg mass, feed conversion ratio, and
      egg color were analyzed every 2 wk. Birds were weighed every 4 wk until
      completion of the study. Birds hatched from TT eggs had significantly increased
      BW throughout the experimental period. Hen-day egg production was significantly
      different when compared with the NT treatment at 19 and 20 wk of age. Eggshell
      color was also found to be significantly different for the NT and TT groups with
      TT eggs being significantly further from true white. Selection of progeny based
      on eggshell color may be a criterion for selecting white egg layers as layers
      hatched from TT eggs resulted in more off-color eggs, which may affect consumer
      acceptance for buying white table eggs. 

PMID- 24931966
TI  - Gene expression of heat shock protein 70 and antioxidant enzymes, oxidative
      status, and meat oxidative stability of cyclically heat-challenged finishing
      broilers fed Origanum compactum and Curcuma xanthorrhiza essential oils.
AB  - Heat stress in poultry is a serious problem in many countries and has been
      associated with oxidative stress. Hence, nutritional interventions with
      antioxidants might be beneficial. Therefore, the effects of dietary Curcuma
      xanthorrhiza (CX) and Origanum compactum (OC) essential oils on mRNA levels of
      heat shock protein 70 and antioxidant enzymes, oxidative status, and meat
      oxidative stability of heat-challenged broilers were studied. Starting on d 25 of
      age, a control diet and 4 diets containing 200 or 400 mg/kg feed of CX or OC
      (CX200, CX400, OC200, OC400 diets) were fed to 3 pen replicates of 20 Ross 308
      chickens each. From d 28 of age on, the temperature was increased from 22 to 34
      degrees C with 50% RH for 5 h daily during 2 wk. Dietary CX or OC did not affect
      zootechnical performance. Feeding CX400 and both levels of OC increased the a*
      value in stored breast meat (P < 0.05), and OC diets tended to decrease the
      thiobarbituric acid reactive substances values in fresh breast meat (P = 0.061).
      Compared with control, at d 31, feeding CX400 and OC400 reduced mRNA levels of
      heat shock protein 70 and increased mRNA levels of catalase in kidney and liver
      (P < 0.05). The mRNA levels of superoxide dismutase were increased at d 31 on the
      OC400 diet in kidney and on the CX400 diet in heart (P < 0.05). In heart, at d
      31, both dietary levels of CX and OC200 resulted in higher glutathione peroxidase
      activity (P < 0.05). Feeding CX400 increased superoxide dismutase activity in
      liver, kidney, and heart at d 31 (P < 0.05). Catalase activity was increased in
      the CX200 and OC400 groups at d 42 (P < 0.05). Feeding CX at both levels and
      OC200 decreased plasma malondialdehyde concentrations at d 42 (P < 0.05). In
      conclusion, dietary essential oils rich in simple phenolic compounds offer
      potential for improving the antioxidant defense against heat stress-induced
      changes. 

PMID- 24931967
TI  - Spatial heterogeneity and stability of bacterial community in the
      gastrointestinal tracts of broiler chickens.
AB  - Bacterial communities in the different regions of gastrointestinal tract (GIT) of
      broiler chickens were analyzed by pyrosequencing approach to understand microbial
      composition and diversity. The DNA samples extracted from 7 different regions
      along the GIT were subjected to bacterial-community analysis by pyrosequencing of
      the V1-V3 region of 16S rRNA gene. Major bacterial phyla in the chicken-gut
      microbiota included Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria,
      and Acidobacteria, but Firmicutes were mostly dominant (67.3 +/- 16.1% of the
      total sequence reads identified). Among Firmicutes, Lactobacillales, including
      the genera Lactobacillus and Enterococcus, were the most dominant (51.8 +/- 34.5%
      of the total sequence reads identified) from the crop to ileum. In contrast, in
      the cecum and large intestine, those genera were rarely detected, and
      Clostridiales were dominant (55.9 +/- 31.4%). Fast UniFrac analysis showed that
      microbial communities from the crop to jejunum of the same individual chicken
      were grouped together, and those from ileum, cecum, and large intestine were
      clustered in a more GIT-specific manner. The numbers of shared operational
      taxonomic units between the neighboring segments of GIT were low, ranging from
      2.9 to 20.3%. However, the abundance of shared operational taxonomic units in
      each segment was relatively high, ranging from 61.7 to 85.0%, suggesting that
      substantial proportions of microbial communities were shared between each segment
      and its neighboring segments, comprising a core microbiota. Our results suggested
      that the microbial communities of 7 main segments in the chicken GIT were
      distinctive according to both individuals and the different segments of GIT, but
      their stability was maintained along the GIT. 

PMID- 24931968
TI  - Effect of free-range days on a local chicken breed: growth performance, carcass
      yield, meat quality, and lymphoid organ index.
AB  - An experiment was conducted to evaluate the effect of free-range days on growth
      performance, carcass yield, meat quality, and lymphoid organ index of a local
      chicken breed. In total, 1,000 one-day-old male Suqin yellow chickens were raised
      for 21 d. On d 21, 720 birds with similar BW (536 +/- 36 g) were selected and
      randomly assigned to free-range treatment at 21, 28, 35, and 42 d of age
      (assigned to free-range treatment for 21, 14, 7, and 0 d, respectively). Each
      treatment was represented by 5 replicates (pens) containing 36 birds (180 birds
      per treatment). All the birds were raised in indoor floor pens measuring 1.42 *
      1.42 m (2 m(2), 18 birds/m(2)) in conventional poultry research houses before
      free-range treatment. In the free-range treatment, the chickens were raised in
      indoor floor houses measuring 3 * 5 m (15 m(2), 2.4 birds/m(2)). In addition,
      they also had an outdoor free-range paddock measuring 3 * 8 m (24 m(2), 1.5
      birds/m(2)). The BW of birds after being assigned to free-range treatment for 7 d
      decreased significantly compared with that in the conventional treatment (P <
      0.05). However, there was no effect of the free-range days on the BW at 42 d of
      age (P > 0.05). The daily weight gain, feed per gain, daily feed intake, and
      mortality from 21 to 42 d of age were unaffected by free-range days (P > 0.05).
      At 42 d of age, the breast yield increased linearly with increasing free-range
      days (P < 0.05), whereas the thigh, leg, thigh bone, and foot yields decreased
      linearly (P < 0.05). The lung yield showed a significant increasing and then
      decreasing quadratic response to increasing free-range days (P < 0.05). The water
      holding capacity of the thigh muscle decreased linearly with increasing free
      range days (P < 0.05), whereas there was no significant difference in the meat
      color, shear force, and muscle pH (P > 0.05). The absolute thymus weight and
      thymus:BW ratio showed a significant increasing and then decreasing quadratic
      response to increasing free-range days (P < 0.05). The findings of this study
      suggest that increasing free-range days advantageously affects breast yield, but
      decreases thigh, leg, thigh bone, and foot yields as well as the water-holding
      capacity of thigh. No evidence was found that increasing free-range days caused
      changes in growth performance, meat quality, and lymphoid organs except for
      changes in water-holding capacity and thymus. 

PMID- 24931969
TI  - Yolk sac fatty acid composition, yolk absorption, embryo development, and chick
      quality during incubation in eggs from young and old broiler breeders.
AB  - The objective of the present study was to examine the changes in yolk and yolk
      sac fatty acid composition and also to investigate egg content, yolk absorption,
      embryo development during incubation, and chick quality at hatch in eggs from 36-
      and 52-wk-old broiler breeders. The fatty acid profiles of the yolk, the yolk sac
      of embryos, and the residual yolk sac of chicks were analyzed before incubation,
      on d 18, and at hatch, respectively. Yolk sac weight, and embryo weight and
      length were measured on d 18, and chick weight and length were measured at hatch.
      Egg weight, yolk and albumen weight, yolk percentage, and yolk:albumen ratio
      increased as breeder age increased, but the albumen percentage decreased. Yolk
      absorption in absolute value (g) was higher in embryos from the old flock on d 18
      and at hatch. Relative yolk absorption was similar between age groups on d 18,
      whereas it was higher in the young flock at hatch. Breeder age affected the yolk
      sac weight and was higher in the old flock during incubation. Embryo or chick
      weight and length, and yolk-free BW were affected by breeder age during
      incubation. These parameters were higher in the old flock with a difference of
      3.7 g, 0.8 cm, and 2.6 g, respectively, on d 18 and 7.4 g, 1.4 cm, and 6.3 g,
      respectively, at hatch compared with the young flock. The effect of breeder age
      on fatty acid composition differed significantly by sampling day. Palmitic,
      stearic, oleic, and linoleic acids were major fatty acids in the fresh yolk,
      ranging from 13.02 to 29.24%. These were followed by palmitoleic and arachidonic
      acids ranging from 1.24 to 7.04%, with the remaining fatty acids below 1%. Higher
      concentrations of myristic, palmitoleic, and oleic acids and lower concentrations
      of heptadeconoic, stearic, linoleic, and arachidonic acids were found in the
      residual yolk sac of the young flock than the old flock. The results showed
      preferentially selective absorption of some fatty acids by the embryo during
      incubation. 

PMID- 24931970
TI  - 25-Hydroxycholecalciferol supplementation improves growth performance and
      decreases inflammation during an experimental lipopolysaccharide injection.
AB  - Three experiments were conducted to study the effects of 25
      hydroxycholecalciferol supplementation on BW gain, IL-1beta, and 1alpha
      hydroxylase mRNA expression in different organs of broiler chickens following a
      lipopolysaccharide (LPS) injection. In experiment I, birds were fed a basal diet
      supplemented with either cholecalciferol (3,000 IU/kg) or 25
      hydroxycholecalciferol (69 ug/kg). At 21 and 35 d of age, birds were injected
      with LPS. Post-LPS injection, birds supplemented with 25-hydroxycholecalciferol
      gained approximately 2.5% (P = 0.03) and 3.8% (P < 0.01), respectively, more BW
      than the birds supplemented with cholecalciferol over the 24-h period. In
      experiment II, birds were fed basal diets supplemented with 25
      hydroxycholecalciferol at 6.25, 25, and 50 ug/kg of feed or cholecalciferol at
      250 IU/kg of feed. At 35 d of age, birds were injected with LPS. Birds fed 25
      hydroxycholecalciferol at 25 and 50 ug/kg and injected with LPS had approximately
      7-fold and 3-fold less (P = 0.010) IL-1beta mRNA in the liver compared with those
      birds fed 6.25 ug/kg of 25-hydroxycholecalciferol and the cholecalciferol (250
      IU/kg) group. In experiment III, birds were fed a basal diet supplemented with
      either cholecalciferol (3,000 IU/kg) or 25-hydroxycholecalciferol (69 ug/kg). At
      28 d of age, birds were fed 25-hydroxycholecalciferol and injected with LPS had
      1.1-fold less (P < 0.01) IL-1beta mRNA in the liver than the cholecalciferol-fed
      group. After an LPS injection, birds supplemented with 25-hydroxycholecalciferol
      had increased 1alpha-hydroxylase mRNA amounts in the liver (P = 0.07). In
      conclusion, 25-hydroxycholecalciferol supplementation at higher doses improved
      growth performance and decreased inflammatory gene IL-1beta mRNA amounts in the
      liver post-LPS injection. 

PMID- 24931971
TI  - Low molecular weight bioactive peptides derived from the enzymatic hydrolysis of
      collagen after isoelectric solubilization/precipitation process of turkey by
      products.
AB  - A process based on the isoelectric solubilization/precipitation (ISP) method was
      developed to recover collagen from low value poultry by-products. The application
      of the ISP process to turkey heads generated protein isolates and an insoluble
      biomass that was used to extract collagen. Isolated turkey head collagen was then
      enzymatically hydrolyzed for different time periods using alcalase, flavorzyme,
      and trypsin. The enzymatic hydrolysis approaches consisted of digesting collagen
      with each one of the 3 enzymes alone (alcalase, flavorzyme, or trypsin), or one
      of the 3 combinations of 2 enzymes (alcalase/flavorzyme, alcalase/trypsin, or
      flavorzyme/trypsin), or a cocktail of all 3 enzymes together
      (alcalase/flavorzyme/trypsin). The molecular weight distribution of turkey head
      collagen hydrolysates was determined using size exclusion chromatography and
      matrix-assisted laser desorption ionization-time of flight-mass spectrometry. The
      enzyme cocktail produced collagen hydrolysates with the greatest amount of low
      molecular weight peptides ranging from 555.26 to 2,093.74 Da. These collagen
      peptides showed excellent solubility over a wide pH range (2 -: 8) and were able
      to bind cholic and deoxycholic acids and significantly (P < 0.05) inhibited
      plasma amine oxidase in a dose- and time-dependent manner. The ISP process
      combined with enzyme cocktail hydrolysis represents a potential new way to
      produce low molecular weight bioactive collagen peptides from low value poultry
      by-products. 

PMID- 24931972
TI  - Computational biology and bioinformatics.

PMID- 24931974
TI  - Methods for time series analysis of RNA-seq data with application to human Th17
      cell differentiation.
AB  - MOTIVATION: Gene expression profiling using RNA-seq is a powerful technique for
      screening RNA species' landscapes and their dynamics in an unbiased way. While
      several advanced methods exist for differential expression analysis of RNA-seq
      data, proper tools to anal.yze RNA-seq time-course have not been proposed.
      RESULTS: In this study, we use RNA-seq to measure gene expression during the
      early human T helper 17 (Th17) cell differentiation and T-: cell activation
      (Th0). To quantify Th17-: specific gene expression dynamics, we present a novel
      statistical methodology, DyNB, for analyzing time-course RNA-seq data. We use non
      parametric Gaussian processes to model temporal correlation in gene expression
      and combine that with negative binomial likelihood for the count data. To account
      for experiment-: specific biases in gene expression dynamics, such as differences
      in cell differentiation efficiencies, we propose a method to rescale the dynamics
      between replicated measurements. We develop an MCMC sampling method to make
      inference of differential expression dynamics between conditions. DyNB identifies
      several known and novel genes involved in Th17 differentiation. Analysis of
      differentiation efficiencies revealed consistent patterns in gene expression
      dynamics between different cultures. We use qRT-PCR to validate differential
      expression and differentiation efficiencies for selected genes. Comparison of the
      results with those obtained via traditional timepoint-: wise analysis shows that
      time-course analysis together with time rescaling between cultures identifies
      differentially expressed genes which would not otherwise be detected.
      AVAILABILITY: An implementation of the proposed computational methods will be
      available at http://research.ics.aalto.fi/csb/software/

PMID- 24931973
TI  - Cross-study validation for the assessment of prediction algorithms.
AB  - MOTIVATION: Numerous competing algorithms for prediction in high-dimensional
      settings have been developed in the statistical and machine-learning literature.
      Learning algorithms and the prediction models they generate are typically
      evaluated on the basis of cross-validation error estimates in a few exemplary
      datasets. However, in most applications, the ultimate goal of prediction modeling
      is to provide accurate predictions for independent samples obtained in different
      settings. Cross-validation within exemplary datasets may not adequately reflect
      performance in the broader application context. METHODS: We develop and implement
      a systematic approach to 'cross-study validation', to replace or supplement
      conventional cross-validation when evaluating high-dimensional prediction models
      in independent datasets. We illustrate it via simulations and in a collection of
      eight estrogen-receptor positive breast cancer microarray gene-expression
      datasets, where the objective is predicting distant metastasis-free survival
      (DMFS). We computed the C-index for all pairwise combinations of training and
      validation datasets. We evaluate several alternatives for summarizing the
      pairwise validation statistics, and compare these to conventional cross
      validation. RESULTS: Our data-driven simulations and our application to survival
      prediction with eight breast cancer microarray datasets, suggest that standard
      cross-validation produces inflated discrimination accuracy for all algorithms
      considered, when compared to cross-study validation. Furthermore, the ranking of
      learning algorithms differs, suggesting that algorithms performing best in cross
      validation may be suboptimal when evaluated through independent validation.
      AVAILABILITY: The survHD: Survival in High Dimensions package
      (http://www.bitbucket.org/lwaldron/survhd) will be made available through
      Bioconductor.

PMID- 24931975
TI  - Deep learning of the tissue-regulated splicing code.
AB  - MOTIVATION: Alternative splicing (AS) is a regulated process that directs the
      generation of different transcripts from single genes. A computational model that
      can accurately predict splicing patterns based on genomic features and cellular
      context is highly desirable, both in understanding this widespread phenomenon,
      and in exploring the effects of genetic variations on AS. METHODS: Using a deep
      neural network, we developed a model inferred from mouse RNA-Seq data that can
      predict splicing patterns in individual tissues and differences in splicing
      patterns across tissues. Our architecture uses hidden variables that jointly
      represent features in genomic sequences and tissue types when making predictions.
      A graphics processing unit was used to greatly reduce the training time of our
      models with millions of parameters. RESULTS: We show that the deep architecture
      surpasses the performance of the previous Bayesian method for predicting AS
      patterns. With the proper optimization procedure and selection of
      hyperparameters, we demonstrate that deep architectures can be beneficial, even
      with a moderately sparse dataset. An analysis of what the model has learned in
      terms of the genomic features is presented.

PMID- 24931976
TI  - Functional association networks as priors for gene regulatory network inference.
AB  - MOTIVATION: Gene regulatory network (GRN) inference reveals the influences genes
      have on one another in cellular regulatory systems. If the experimental data are
      inadequate for reliable inference of the network, informative priors have been
      shown to improve the accuracy of inferences. RESULTS: This study explores the
      potential of undirected, confidence-weighted networks, such as those in
      functional association databases, as a prior source for GRN inference. Such
      networks often erroneously indicate symmetric interaction between genes and may
      contain mostly correlation-based interaction information. Despite these
      drawbacks, our testing on synthetic datasets indicates that even noisy priors
      reflect some causal information that can improve GRN inference accuracy. Our
      analysis on yeast data indicates that using the functional association databases
      FunCoup and STRING as priors can give a small improvement in GRN inference
      accuracy with biological data.

PMID- 24931977
TI  - Graph-regularized dual Lasso for robust eQTL mapping.
AB  - MOTIVATION: As a promising tool for dissecting the genetic basis of complex
      traits, expression quantitative trait loci (eQTL) mapping has attracted
      increasing research interest. An important issue in eQTL mapping is how to
      effectively integrate networks representing interactions among genetic markers
      and genes. Recently, several Lasso-based methods have been proposed to leverage
      such network information. Despite their success, existing methods have three
      common limitations: (i) a preprocessing step is usually needed to cluster the
      networks; (ii) the incompleteness of the networks and the noise in them are not
      considered; (iii) other available information, such as location of genetic
      markers and pathway information are not integrated. RESULTS: To address the
      limitations of the existing methods, we propose Graph-regularized Dual Lasso
      (GDL), a robust approach for eQTL mapping. GDL integrates the correlation
      structures among genetic markers and traits simultaneously. It also takes into
      account the incompleteness of the networks and is robust to the noise. GDL
      utilizes graph-based regularizers to model the prior networks and does not
      require an explicit clustering step. Moreover, it enables further refinement of
      the partial and noisy networks. We further generalize GDL to incorporate the
      location of genetic makers and gene-pathway information. We perform extensive
      experimental evaluations using both simulated and real datasets. Experimental
      results demonstrate that the proposed methods can effectively integrate various
      available priori knowledge and significantly outperform the state-of-the-art eQTL
      mapping methods. AVAILABILITY: Software for both C++ version and Matlab version
      is available at http://www.cs.unc.edu/~weicheng/.

PMID- 24931978
TI  - Pipasic: similarity and expression correction for strain-level identification and
      quantification in metaproteomics.
AB  - MOTIVATION: Metaproteomic analysis allows studying the interplay of organisms or
      functional groups and has become increasingly popular also for diagnostic
      purposes. However, difficulties arise owing to the high sequence similarity
      between related organisms. Further, the state of conservation of proteins between
      species can be correlated with their expression level, which can lead to
      significant bias in results and interpretation. These challenges are similar but
      not identical to the challenges arising in the analysis of metagenomic samples
      and require specific solutions. RESULTS: We introduce Pipasic (peptide intensity
      weighted proteome abundance similarity correction) as a tool that corrects
      identification and spectral counting-based quantification results using peptide
      similarity estimation and expression level weighting within a non-negative lasso
      framework. Pipasic has distinct advantages over approaches only regarding unique
      peptides or aggregating results to the lowest common ancestor, as demonstrated on
      examples of viral diagnostics and an acid mine drainage dataset. AVAILABILITY AND
      IMPLEMENTATION: Pipasic source code is freely available from
      https://sourceforge.net/projects/pipasic/. CONTACT: RenardB@rki.de SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 24931979
TI  - Metabolite identification through multiple kernel learning on fragmentation
      trees.
AB  - MOTIVATION: Metabolite identification from tandem mass spectrometric data is a
      key task in metabolomics. Various computational methods have been proposed for
      the identification of metabolites from tandem mass spectra. Fragmentation tree
      methods explore the space of possible ways in which the metabolite can fragment,
      and base the metabolite identification on scoring of these fragmentation trees.
      Machine learning methods have been used to map mass spectra to molecular
      fingerprints; predicted fingerprints, in turn, can be used to score candidate
      molecular structures. RESULTS: Here, we combine fragmentation tree computations
      with kernel-based machine learning to predict molecular fingerprints and identify
      molecular structures. We introduce a family of kernels capturing the similarity
      of fragmentation trees, and combine these kernels using recently proposed
      multiple kernel learning approaches. Experiments on two large reference datasets
      show that the new methods significantly improve molecular fingerprint prediction
      accuracy. These improvements result in better metabolite identification, doubling
      the number of metabolites ranked at the top position of the candidates list.

PMID- 24931980
TI  - Metabolome-scale prediction of intermediate compounds in multistep metabolic
      pathways with a recursive supervised approach.
AB  - MOTIVATION: Metabolic pathway analysis is crucial not only in metabolic
      engineering but also in rational drug design. However, the
      biosynthetic/biodegradation pathways are known only for a small portion of
      metabolites, and a vast amount of pathways remain uncharacterized. Therefore, an
      important challenge in metabolomics is the de novo reconstruction of potential
      reaction networks on a metabolome-scale. RESULTS: In this article, we develop a
      novel method to predict the multistep reaction sequences for de novo
      reconstruction of metabolic pathways in the reaction-filling framework. We
      propose a supervised approach to learn what we refer to as 'multistep reaction
      sequence likeness', i.e. whether a compound-compound pair is possibly converted
      to each other by a sequence of enzymatic reactions. In the algorithm, we propose
      a recursive procedure of using step-specific classifiers to predict the
      intermediate compounds in the multistep reaction sequences, based on chemical
      substructure fingerprints/descriptors of compounds. We further demonstrate the
      usefulness of our proposed method on the prediction of enzymatic reaction
      networks from a metabolome-scale compound set and discuss characteristic features
      of the extracted chemical substructure transformation patterns in multistep
      reaction sequences. Our comprehensively predicted reaction networks help to fill
      the metabolic gap and to infer new reaction sequences in metabolic pathways.
      AVAILABILITY AND IMPLEMENTATION: Materials are available for free at
      http://web.kuicr.kyoto-u.ac.jp/supp/kot/ismb2014/

PMID- 24931981
TI  - MIRA: mutual information-based reporter algorithm for metabolic networks.
AB  - MOTIVATION: Discovering the transcriptional regulatory architecture of the
      metabolism has been an important topic to understand the implications of
      transcriptional fluctuations on metabolism. The reporter algorithm (RA) was
      proposed to determine the hot spots in metabolic networks, around which
      transcriptional regulation is focused owing to a disease or a genetic
      perturbation. Using a z-score-based scoring scheme, RA calculates the average
      statistical change in the expression levels of genes that are neighbors to a
      target metabolite in the metabolic network. The RA approach has been used in
      numerous studies to analyze cellular responses to the downstream genetic changes.
      In this article, we propose a mutual information-based multivariate reporter
      algorithm (MIRA) with the goal of eliminating the following problems in detecting
      reporter metabolites: (i) conventional statistical methods suffer from small
      sample sizes, (ii) as z-score ranges from minus to plus infinity, calculating
      average scores can lead to canceling out opposite effects and (iii) analyzing
      genes one by one, then aggregating results can lead to information loss. MIRA is
      a multivariate and combinatorial algorithm that calculates the aggregate
      transcriptional response around a metabolite using mutual information. We show
      that MIRA's results are biologically sound, empirically significant and more
      reliable than RA. RESULTS: We apply MIRA to gene expression analysis of six
      knockout strains of Escherichia coli and show that MIRA captures the underlying
      metabolic dynamics of the switch from aerobic to anaerobic respiration. We also
      apply MIRA to an Autism Spectrum Disorder gene expression dataset. Results
      indicate that MIRA reports metabolites that highly overlap with recently found
      metabolic biomarkers in the autism literature. Overall, MIRA is a promising
      algorithm for detecting metabolic drug targets and understanding the relation
      between gene expression and metabolic activity. AVAILABILITY AND IMPLEMENTATION:
      The code is implemented in C# language using .NET framework. Project is available
      upon request.

PMID- 24931982
TI  - GRASP: analysis of genotype-phenotype results from 1390 genome-wide association
      studies and corresponding open access database.
AB  - SUMMARY: We created a deeply extracted and annotated database of genome-wide
      association studies (GWAS) results. GRASP v1.0 contains >6.2 million SNP
      phenotype association from among 1390 GWAS studies. We re-annotated GWAS results
      with 16 annotation sources including some rarely compared to GWAS results (e.g.
      RNAediting sites, lincRNAs, PTMs). MOTIVATION: To create a high-quality resource
      to facilitate further use and interpretation of human GWAS results in order to
      address important scientific questions. RESULTS: GWAS have grown exponentially,
      with increases in sample sizes and markers tested, and continuing bias toward
      European ancestry samples. GRASP contains >100 000 phenotypes, roughly: eQTLs
      (71.5%), metabolite QTLs (21.2%), methylation QTLs (4.4%) and diseases,
      biomarkers and other traits (2.8%). cis-eQTLs, meQTLs, mQTLs and MHC region SNPs
      are highly enriched among significant results. After removing these categories,
      GRASP still contains a greater proportion of studies and results than comparable
      GWAS catalogs. Cardiovascular disease and related risk factors pre-dominate
      remaining GWAS results, followed by immunological, neurological and cancer
      traits. Significant results in GWAS display a highly gene-centric tendency. Sex
      chromosome X (OR = 0.18[0.16-0.20]) and Y (OR = 0.003[0.001-0.01]) genes are
      depleted for GWAS results. Gene length is correlated with GWAS results at nominal
      significance (P <= 0.05) levels. We show this gene-length correlation decays at
      increasingly more stringent P-value thresholds. Potential pleotropic genes and
      SNPs enriched for multi-phenotype association in GWAS are identified. However, we
      note possible population stratification at some of these loci. Finally, via re
      annotation we identify compelling functional hypotheses at GWAS loci, in some
      cases unrealized in studies to date. CONCLUSION: Pooling summary-level GWAS
      results and re-annotating with bioinformatics predictions and molecular features
      provides a good platform for new insights. AVAILABILITY: The GRASP database is
      available at http://apps.nhlbi.nih.gov/grasp.

PMID- 24931983
TI  - EPIQ-efficient detection of SNP-SNP epistatic interactions for quantitative
      traits.
AB  - MOTIVATION: Gene-gene interactions are of potential biological and medical
      interest, as they can shed light on both the inheritance mechanism of a trait and
      on the underlying biological mechanisms. Evidence of epistatic interactions has
      been reported in both humans and other organisms. Unlike single-locus genome-wide
      association studies (GWAS), which proved efficient in detecting numerous genetic
      loci related with various traits, interaction-based GWAS have so far produced
      very few reproducible discoveries. Such studies introduce a great computational
      and statistical burden by necessitating a large number of hypotheses to be tested
      including all pairs of single nucleotide polymorphisms (SNPs). Thus, many
      software tools have been developed for interaction-based case-control studies,
      some leading to reliable discoveries. For quantitative data, on the other hand,
      only a handful of tools exist, and the computational burden is still substantial.
      RESULTS: We present an efficient algorithm for detecting epistasis in
      quantitative GWAS, achieving a substantial runtime speedup by avoiding the need
      to exhaustively test all SNP pairs using metric embedding and random projections.
      Unlike previous metric embedding methods for case-control studies, we introduce a
      new embedding, where each SNP is mapped to two Euclidean spaces. We implemented
      our method in a tool named EPIQ (EPIstasis detection for Quantitative GWAS), and
      we show by simulations that EPIQ requires hours of processing time where other
      methods require days and sometimes weeks. Applying our method to a dataset from
      the Ludwigshafen risk and cardiovascular health study, we discovered a pair of
      SNPs with a near-significant interaction (P = 2.2 * 10(-13)), in only 1.5 h on 10
      processors. AVAILABILITY: https://github.com/yaarasegre/EPIQ

PMID- 24931984
TI  - Detecting independent and recurrent copy number aberrations using interval
      graphs.
AB  - MOTIVATION: Somatic copy number aberrations SCNAS: are frequent in cancer
      genomes, but many of these are random, passenger events. A common strategy to
      distinguish functional aberrations from passengers is to identify those
      aberrations that are recurrent across multiple samples. However, the extensive
      variability in the length and position of SCNA: s makes the problem of
      identifying recurrent aberrations notoriously difficult. RESULTS: We introduce a
      combinatorial approach to the problem of identifying independent and recurrent
      SCNA: s, focusing on the key challenging of separating the overlaps in
      aberrations across individuals into independent events. We derive independent and
      recurrent SCNA: s as maximal cliques in an interval graph constructed from
      overlaps between aberrations. We efficiently enumerate all such cliques, and
      derive a dynamic programming algorithm to find an optimal selection of non
      overlapping cliques, resulting in a very fast algorithm, which we call RAIG
      (Recurrent Aberrations from Interval Graphs). We show that RAIG outperforms other
      methods on simulated data and also performs well on data from three cancer types
      from The Cancer Genome Atlas (TCGA). In contrast to existing approaches that
      employ various heuristics to select independent aberrations, RAIG optimizes a
      well-defined objective function. We show that this allows RAIG to identify rare
      aberrations that are likely functional, but are obscured by overlaps with larger
      passenger aberrations. AVAILABILITY: http://compbio.cs.brown.edu/software.

PMID- 24931986
TI  - Probabilistic method for detecting copy number variation in a fetal genome using
      maternal plasma sequencing.
AB  - MOTIVATION: The past several years have seen the development of methodologies to
      identify genomic variation within a fetus through the non-invasive sequencing of
      maternal blood plasma. These methods are based on the observation that maternal
      plasma contains a fraction of DNA (typically 5-15%) originating from the fetus,
      and such methodologies have already been used for the detection of whole
      chromosome events (aneuploidies), and to a more limited extent for smaller
      (typically several megabases long) copy number variants (CNVs). RESULTS: Here we
      present a probabilistic method for non-invasive analysis of de novo CNVs in fetal
      genome based on maternal plasma sequencing. Our novel method combines three types
      of information within a unified Hidden Markov Model: the imbalance of allelic
      ratios at SNP positions, the use of parental genotypes to phase nearby SNPs and
      depth of coverage to better differentiate between various types of CNVs and
      improve precision. Our simulation results, based on in silico introduction of
      novel CNVs into plasma samples with 13% fetal DNA concentration, demonstrate a
      sensitivity of 90% for CNVs >400 kb (with 13 calls in an unaffected genome), and
      40% for 50-400 kb CNVs (with 108 calls in an unaffected genome). AVAILABILITY AND
      IMPLEMENTATION: Implementation of our model and data simulation method is
      available at http://github.com/compbio-UofT/fCNV.

PMID- 24931985
TI  - Privacy preserving protocol for detecting genetic relatives using rare variants.
AB  - MOTIVATION: High-throughput sequencing technologies have impacted many areas of
      genetic research. One such area is the identification of relatives from genetic
      data. The standard approach for the identification of genetic relatives collects
      the genomic data of all individuals and stores it in a database. Then, each pair
      of individuals is compared to detect the set of genetic relatives, and the
      matched individuals are informed. The main drawback of this approach is the
      requirement of sharing your genetic data with a trusted third party to perform
      the relatedness test. RESULTS: In this work, we propose a secure protocol to
      detect the genetic relatives from sequencing data while not exposing any
      information about their genomes. We assume that individuals have access to their
      genome sequences but do not want to share their genomes with anyone else. Unlike
      previous approaches, our approach uses both common and rare variants which
      provide the ability to detect much more distant relationships securely. We use a
      simulated data generated from the 1000 genomes data and illustrate that we can
      easily detect up to fifth degree cousins which was not possible using the
      existing methods. We also show in the 1000 genomes data with cryptic
      relationships that our method can detect these individuals. AVAILABILITY: The
      software is freely available for download at http://genetics.cs.ucla.edu/crypto/.

PMID- 24931987
TI  - New directions for diffusion-based network prediction of protein function:
      incorporating pathways with confidence.
AB  - MOTIVATION: It has long been hypothesized that incorporating models of network
      noise as well as edge directions and known pathway information into the
      representation of protein-protein interaction (PPI) networks might improve their
      utility for functional inference. However, a simple way to do this has not been
      obvious. We find that diffusion state distance (DSD), our recent diffusion-based
      metric for measuring dissimilarity in PPI networks, has natural extensions that
      incorporate confidence, directions and can even express coherent pathways by
      calculating DSD on an augmented graph. RESULTS: We define three incremental
      versions of DSD which we term cDSD, caDSD and capDSD, where the capDSD matrix
      incorporates confidence, known directed edges, and pathways into the measure of
      how similar each pair of nodes is according to the structure of the PPI network.
      We test four popular function prediction methods (majority vote, weighted
      majority vote, multi-way cut and functional flow) using these different matrices
      on the Baker's yeast PPI network in cross-validation. The best performing method
      is weighted majority vote using capDSD. We then test the performance of our
      augmented DSD methods on an integrated heterogeneous set of protein association
      edges from the STRING database. The superior performance of capDSD in this
      context confirms that treating the pathways as probabilistic units is more
      powerful than simply incorporating pathway edges independently into the network.
      AVAILABILITY: All source code for calculating the confidences, for extracting
      pathway information from KEGG XML files, and for calculating the cDSD, caDSD and
      capDSD matrices are available from http://dsd.cs.tufts.edu/capdsd

PMID- 24931988
TI  - DrugComboRanker: drug combination discovery based on target network analysis.
AB  - MOTIVATION: Currently there are no curative anticancer drugs, and drug resistance
      is often acquired after drug treatment. One of the reasons is that cancers are
      complex diseases, regulated by multiple signaling pathways and cross talks among
      the pathways. It is expected that drug combinations can reduce drug resistance
      and improve patients' outcomes. In clinical practice, the ideal and feasible drug
      combinations are combinations of existing Food and Drug Administration-approved
      drugs or bioactive compounds that are already used on patients or have entered
      clinical trials and passed safety tests. These drug combinations could directly
      be used on patients with less concern of toxic effects. However, there is so far
      no effective computational approach to search effective drug combinations from
      the enormous number of possibilities. RESULTS: In this study, we propose a novel
      systematic computational tool DRUGCOMBORANKER: to prioritize synergistic drug
      combinations and uncover their mechanisms of action. We first build a drug
      functional network based on their genomic profiles, and partition the network
      into numerous drug network communities by using a Bayesian non-negative matrix
      factorization approach. As drugs within overlapping community share common
      mechanisms of action, we next uncover potential targets of drugs by applying a
      recommendation system on drug communities. We meanwhile build disease-specific
      signaling networks based on patients' genomic profiles and interactome data. We
      then identify drug combinations by searching drugs whose targets are enriched in
      the complementary signaling modules of the disease signaling network. The novel
      method was evaluated on lung adenocarcinoma and endocrine receptor positive
      breast cancer, and compared with other drug combination approaches. These case
      studies discovered a set of effective drug combinations top ranked in our
      prediction list, and mapped the drug targets on the disease signaling network to
      highlight the mechanisms of action of the drug combinations. AVAILABILITY AND
      IMPLEMENTATION: The program is available on request.

PMID- 24931989
TI  - Scale-space measures for graph topology link protein network architecture to
      function.
AB  - MOTIVATION: The network architecture of physical protein interactions is an
      important determinant for the molecular functions that are carried out within
      each cell. To study this relation, the network architecture can be characterized
      by graph topological characteristics such as shortest paths and network hubs.
      These characteristics have an important shortcoming: they do not take into
      account that interactions occur across different scales. This is important
      because some cellular functions may involve a single direct protein interaction
      (small scale), whereas others require more and/or indirect interactions, such as
      protein complexes (medium scale) and interactions between large modules of
      proteins (large scale). RESULTS: In this work, we derive generalized scale-aware
      versions of known graph topological measures based on diffusion kernels. We apply
      these to characterize the topology of networks across all scales simultaneously,
      generating a so-called graph topological scale-space. The comprehensive physical
      interaction network in yeast is used to show that scale-space based measures
      consistently give superior performance when distinguishing protein functional
      categories and three major types of functional interactions-genetic interaction,
      co-expression and perturbation interactions. Moreover, we demonstrate that graph
      topological scale spaces capture biologically meaningful features that provide
      new insights into the link between function and protein network architecture.
      AVAILABILITY AND IMPLEMENTATION: Matlab(TM) code to calculate the scale-aware
      topological measures (STMs) is available at http://bioinformatics.tudelft.nl/TSSA

PMID- 24931991
TI  - An efficient parallel algorithm for accelerating computational protein design.
AB  - MOTIVATION: Structure-based computational protein design (SCPR) is an important
      topic in protein engineering. Under the assumption of a rigid backbone and a
      finite set of discrete conformations of side-chains, various methods have been
      proposed to address this problem. A popular method is to combine the dead-end
      elimination (DEE) and A* tree search algorithms, which provably finds the global
      minimum energy conformation (GMEC) solution. RESULTS: In this article, we improve
      the efficiency of computing A* heuristic functions for protein design and propose
      a variant of A* algorithm in which the search process can be performed on a
      single GPU in a massively parallel fashion. In addition, we make some efforts to
      address the memory exceeding problem in A* search. As a result, our enhancements
      can achieve a significant speedup of the A*-based protein design algorithm by
      four orders of magnitude on large-scale test data through pre-computation and
      parallelization, while still maintaining an acceptable memory overhead. We also
      show that our parallel A* search algorithm could be successfully combined with
      iMinDEE, a state-of-the-art DEE criterion, for rotamer pruning to further improve
      SCPR with the consideration of continuous side-chain flexibility. AVAILABILITY:
      Our software is available and distributed open-source under the GNU Lesser
      General License Version 2.1 (GNU, February 1999). The source code can be
      downloaded from http://www.cs.duke.edu/donaldlab/osprey.php or
      http://iiis.tsinghua.edu.cn/~compbio/software.html.

PMID- 24931990
TI  - Gene network inference by probabilistic scoring of relationships from a
      factorized model of interactions.
AB  - MOTIVATION: Epistasis analysis is an essential tool of classical genetics for
      inferring the order of function of genes in a common pathway. Typically, it
      considers single and double mutant phenotypes and for a pair of genes observes
      whether a change in the first gene masks the effects of the mutation in the
      second gene. Despite the recent emergence of biotechnology techniques that can
      provide gene interaction data on a large, possibly genomic scale, few methods are
      available for quantitative epistasis analysis and epistasis-based network
      reconstruction. RESULTS: We here propose a conceptually new probabilistic
      approach to gene network inference from quantitative interaction data. The
      approach is founded on epistasis analysis. Its features are joint treatment of
      the mutant phenotype data with a factorized model and probabilistic scoring of
      pairwise gene relationships that are inferred from the latent gene
      representation. The resulting gene network is assembled from scored pairwise
      relationships. In an experimental study, we show that the proposed approach can
      accurately reconstruct several known pathways and that it surpasses the accuracy
      of current approaches. AVAILABILITY AND IMPLEMENTATION: Source code is available
      at http://github.com/biolab/red.

PMID- 24931992
TI  - A statistical approach for inferring the 3D structure of the genome.
AB  - MOTIVATION: Recent technological advances allow the measurement, in a single Hi-C
      experiment, of the frequencies of physical contacts among pairs of genomic loci
      at a genome-wide scale. The next challenge is to infer, from the resulting DNA
      DNA contact maps, accurate 3D models of how chromosomes fold and fit into the
      nucleus. Many existing inference methods rely on multidimensional scaling (MDS),
      in which the pairwise distances of the inferred model are optimized to resemble
      pairwise distances derived directly from the contact counts. These approaches,
      however, often optimize a heuristic objective function and require strong
      assumptions about the biophysics of DNA to transform interaction frequencies to
      spatial distance, and thereby may lead to incorrect structure reconstruction.
      METHODS: We propose a novel approach to infer a consensus 3D structure of a
      genome from Hi-C data. The method incorporates a statistical model of the contact
      counts, assuming that the counts between two loci follow a Poisson distribution
      whose intensity decreases with the physical distances between the loci. The
      method can automatically adjust the transfer function relating the spatial
      distance to the Poisson intensity and infer a genome structure that best explains
      the observed data. RESULTS: We compare two variants of our Poisson method, with
      or without optimization of the transfer function, to four different MDS-based
      algorithms-two metric MDS methods using different stress functions, a non-metric
      version of MDS and ChromSDE, a recently described, advanced MDS method-on a wide
      range of simulated datasets. We demonstrate that the Poisson models reconstruct
      better structures than all MDS-based methods, particularly at low coverage and
      high resolution, and we highlight the importance of optimizing the transfer
      function. On publicly available Hi-C data from mouse embryonic stem cells, we
      show that the Poisson methods lead to more reproducible structures than MDS-based
      methods when we use data generated using different restriction enzymes, and when
      we reconstruct structures at different resolutions. AVAILABILITY AND
      IMPLEMENTATION: A Python implementation of the proposed method is available at
      http://cbio.ensmp.fr/pastis.

PMID- 24931993
TI  - Tertiary structure-based prediction of conformational B-cell epitopes through B
      factors.
AB  - MOTIVATION: B-cell epitope is a small area on the surface of an antigen that
      binds to an antibody. Accurately locating epitopes is of critical importance for
      vaccine development. Compared with wet-lab methods, computational methods have
      strong potential for efficient and large-scale epitope prediction for antigen
      candidates at much lower cost. However, it is still not clear which features are
      good determinants for accurate epitope prediction, leading to the unsatisfactory
      performance of existing prediction methods. METHOD AND RESULTS: We propose a much
      more accurate B-cell epitope prediction method. Our method uses a new feature B
      factor (obtained from X-ray crystallography), combined with other basic
      physicochemical, statistical, evolutionary and structural features of each
      residue. These basic features are extended by a sequence window and a structure
      window. All these features are then learned by a two-stage random forest model to
      identify clusters of antigenic residues and to remove isolated outliers. Tested
      on a dataset of 55 epitopes from 45 tertiary structures, we prove that our method
      significantly outperforms all three existing structure-based epitope predictors.
      Following comprehensive analysis, it is found that features such as B factor,
      relative accessible surface area and protrusion index play an important role in
      characterizing B-cell epitopes. Our detailed case studies on an HIV antigen and
      an influenza antigen confirm that our second stage learning is effective for
      clustering true antigenic residues and for eliminating self-made prediction
      errors introduced by the first-stage learning. AVAILABILITY AND IMPLEMENTATION:
      Source codes are available on request.

PMID- 24931994
TI  - BlockClust: efficient clustering and classification of non-coding RNAs from short
      read RNA-seq profiles.
AB  - SUMMARY: Non-coding RNAs (ncRNAs) play a vital role in many cellular processes
      such as RNA splicing, translation, gene regulation. However the vast majority of
      ncRNAs still have no functional annotation. One prominent approach for putative
      function assignment is clustering of transcripts according to sequence and
      secondary structure. However sequence information is changed by post
      transcriptional modifications, and secondary structure is only a proxy for the
      true 3D conformation of the RNA polymer. A different type of information that
      does not suffer from these issues and that can be used for the detection of RNA
      classes, is the pattern of processing and its traces in small RNA-seq reads data.
      Here we introduce BlockClust, an efficient approach to detect transcripts with
      similar processing patterns. We propose a novel way to encode expression profiles
      in compact discrete structures, which can then be processed using fast graph
      kernel techniques. We perform both unsupervised clustering and develop family
      specific discriminative models; finally we show how the proposed approach is
      scalable, accurate and robust across different organisms, tissues and cell lines.
      AVAILABILITY: The whole BlockClust galaxy workflow including all tool
      dependencies is available at
      http://toolshed.g2.bx.psu.edu/view/rnateam/blockclust_workflow.

PMID- 24931995
TI  - RNA-Skim: a rapid method for RNA-Seq quantification at transcript level.
AB  - MOTIVATION: RNA-Seq technique has been demonstrated as a revolutionary means for
      exploring transcriptome because it provides deep coverage and base pair-level
      resolution. RNA-Seq quantification is proven to be an efficient alternative to
      Microarray technique in gene expression study, and it is a critical component in
      RNA-Seq differential expression analysis. Most existing RNA-Seq quantification
      tools require the alignments of fragments to either a genome or a transcriptome,
      entailing a time-consuming and intricate alignment step. To improve the
      performance of RNA-Seq quantification, an alignment-free method, Sailfish, has
      been recently proposed to quantify transcript abundances using all k-mers in the
      transcriptome, demonstrating the feasibility of designing an efficient alignment
      free method for transcriptome quantification. Even though Sailfish is
      substantially faster than alternative alignment-dependent methods such as
      Cufflinks, using all k-mers in the transcriptome quantification impedes the
      scalability of the method. RESULTS: We propose a novel RNA-Seq quantification
      method, RNA-Skim, which partitions the transcriptome into disjoint transcript
      clusters based on sequence similarity, and introduces the notion of sig-mers,
      which are a special type of k-mers uniquely associated with each cluster. We
      demonstrate that the sig-mer counts within a cluster are sufficient for
      estimating transcript abundances with accuracy comparable with any state-of-the
      art method. This enables RNA-Skim to perform transcript quantification on each
      cluster independently, reducing a complex optimization problem into smaller
      optimization tasks that can be run in parallel. As a result, RNA-Skim uses <4% of
      the k-mers and <10% of the CPU time required by Sailfish. It is able to finish
      transcriptome quantification in <10 min per sample by using just a single thread
      on a commodity computer, which represents >100 speedup over the state-of-the-art
      alignment-based methods, while delivering comparable or higher accuracy.
      AVAILABILITY AND IMPLEMENTATION: The software is available at
      http://www.csbio.unc.edu/rs.

PMID- 24931996
TI  - ExSPAnder: a universal repeat resolver for DNA fragment assembly.
AB  - Next-generation sequencing (NGS) technologies have raised a challenging de novo
      genome assembly problem that is further amplified in recently emerged single-cell
      sequencing projects. While various NGS assemblers can use information from
      several libraries of read-pairs, most of them were originally developed for a
      single library and do not fully benefit from multiple libraries. Moreover, most
      assemblers assume uniform read coverage, condition that does not hold for single
      cell projects where utilization of read-pairs is even more challenging. We have
      developed an exSPAnder algorithm that accurately resolves repeats in the case of
      both single and multiple libraries of read-pairs in both standard and single-cell
      assembly projects. AVAILABILITY AND IMPLEMENTATION:
      http://bioinf.spbau.ru/en/spades

PMID- 24931998
TI  - Ragout-a reference-assisted assembly tool for bacterial genomes.
AB  - SUMMARY: Bacterial genomes are simpler than mammalian ones, and yet assembling
      the former from the data currently generated by high-throughput short-read
      sequencing machines still results in hundreds of contigs. To improve assembly
      quality, recent studies have utilized longer Pacific Biosciences (PacBio) reads
      or jumping libraries to connect contigs into larger scaffolds or help assemblers
      resolve ambiguities in repetitive regions of the genome. However, their
      popularity in contemporary genomic research is still limited by high cost and
      error rates. In this work, we explore the possibility of improving assemblies by
      using complete genomes from closely related species/strains. We present Ragout, a
      genome rearrangement approach, to address this problem. In contrast with most
      reference-guided algorithms, where only one reference genome is used, Ragout uses
      multiple references along with the evolutionary relationship among these
      references in order to determine the correct order of the contigs. Additionally,
      Ragout uses the assembly graph and multi-scale synteny blocks to reduce assembly
      gaps caused by small contigs from the input assembly. In simulations as well as
      real datasets, we believe that for common bacterial species, where many complete
      genome sequences from related strains have been available, the current high
      throughput short-read sequencing paradigm is sufficient to obtain a single high
      quality scaffold for each chromosome. AVAILABILITY: The Ragout software is freely
      available at: https://github.com/fenderglass/Ragout.

PMID- 24931999
TI  - Stochastic EM-based TFBS motif discovery with MITSU.
AB  - MOTIVATION: The Expectation-Maximization (EM) algorithm has been successfully
      applied to the problem of transcription factor binding site (TFBS) motif
      discovery and underlies the most widely used motif discovery algorithms. In the
      wider field of probabilistic modelling, the stochastic EM (sEM) algorithm has
      been used to overcome some of the limitations of the EM algorithm; however, the
      application of sEM to motif discovery has not been fully explored. RESULTS: We
      present MITSU (Motif discovery by ITerative Sampling and Updating), a novel
      algorithm for motif discovery, which combines sEM with an improved approximation
      to the likelihood function, which is unconstrained with regard to the
      distribution of motif occurrences within the input dataset. The algorithm is
      evaluated quantitatively on realistic synthetic data and several collections of
      characterized prokaryotic TFBS motifs and shown to outperform EM and an
      alternative sEM-based algorithm, particularly in terms of site-level positive
      predictive value. AVAILABILITY AND IMPLEMENTATION: Java executable available for
      download at http://www.sourceforge.net/p/mitsu-motif/, supported on Linux/OS X.

PMID- 24932000
TI  - AlignGraph: algorithm for secondary de novo genome assembly guided by closely
      related references.
AB  - MOTIVATION: De novo assemblies of genomes remain one of the most challenging
      applications in next-generation sequencing. Usually, their results are incomplete
      and fragmented into hundreds of contigs. Repeats in genomes and sequencing errors
      are the main reasons for these complications. With the rapidly growing number of
      sequenced genomes, it is now feasible to improve assemblies by guiding them with
      genomes from related species. RESULTS: Here we introduce AlignGraph, an algorithm
      for extending and joining de novo-assembled contigs or scaffolds guided by
      closely related reference genomes. It aligns paired-end (PE) reads and
      preassembled contigs or scaffolds to a close reference. From the obtained
      alignments, it builds a novel data structure, called the PE multipositional de
      Bruijn graph. The incorporated positional information from the alignments and PE
      reads allows us to extend the initial assemblies, while avoiding incorrect
      extensions and early terminations. In our performance tests, AlignGraph was able
      to substantially improve the contigs and scaffolds from several assemblers. For
      instance, 28.7-62.3% of the contigs of Arabidopsis thaliana and human could be
      extended, resulting in improvements of common assembly metrics, such as an
      increase of the N50 of the extendable contigs by 89.9-94.5% and 80.3-165.8%,
      respectively. In another test, AlignGraph was able to improve the assembly of a
      published genome (Arabidopsis strain Landsberg) by increasing the N50 of its
      extendable scaffolds by 86.6%. These results demonstrate AlignGraph's efficiency
      in improving genome assemblies by taking advantage of closely related references.
      AVAILABILITY AND IMPLEMENTATION: The AlignGraph software can be downloaded for
      free from this site: https://github.com/baoe/AlignGraph.

PMID- 24932001
TI  - Accurate viral population assembly from ultra-deep sequencing data.
AB  - MOTIVATION: Next-generation sequencing technologies sequence viruses with ultra
      deep coverage, thus promising to revolutionize our understanding of the
      underlying diversity of viral populations. While the sequencing coverage is high
      enough that even rare viral variants are sequenced, the presence of sequencing
      errors makes it difficult to distinguish between rare variants and sequencing
      errors. RESULTS: In this article, we present a method to overcome the limitations
      of sequencing technologies and assemble a diverse viral population that allows
      for the detection of previously undiscovered rare variants. The proposed method
      consists of a high-fidelity sequencing protocol and an accurate viral population
      assembly method, referred to as Viral Genome Assembler (VGA). The proposed
      protocol is able to eliminate sequencing errors by using individual barcodes
      attached to the sequencing fragments. Highly accurate data in combination with
      deep coverage allow VGA to assemble rare variants. VGA uses an expectation
      maximization algorithm to estimate abundances of the assembled viral variants in
      the population. RESULTS on both synthetic and real datasets show that our method
      is able to accurately assemble an HIV viral population and detect rare variants
      previously undetectable due to sequencing errors. VGA outperforms state-of-the
      art methods for genome-wide viral assembly. Furthermore, our method is the first
      viral assembly method that scales to millions of sequencing reads. AVAILABILITY:
      Our tool VGA is freely available at http://genetics.cs.ucla.edu/vga/

PMID- 24932003
TI  - Inferring gene ontologies from pairwise similarity data.
AB  - MOTIVATION: While the manually curated Gene Ontology (GO) is widely used,
      inferring a GO directly from -omics data is a compelling new problem. Recognizing
      that ontologies are a directed acyclic graph (DAG) of terms and hierarchical
      relations, algorithms are needed that: analyze a full matrix of gene-gene
      pairwise similarities from -omics data; infer true hierarchical structure in
      these data rather than enforcing hierarchy as a computational artifact; and
      respect biological pleiotropy, by which a term in the hierarchy can relate to
      multiple higher level terms. Methods addressing these requirements are just
      beginning to emerge-none has been evaluated for GO inference. METHODS: We
      consider two algorithms [Clique Extracted Ontology (CliXO), LocalFitness] that
      uniquely satisfy these requirements, compared with methods including standard
      clustering. CliXO is a new approach that finds maximal cliques in a network
      induced by progressive thresholding of a similarity matrix. We evaluate each
      method's ability to reconstruct the GO biological process ontology from a
      similarity matrix based on (a) semantic similarities for GO itself or (b) three 
      omics datasets for yeast. RESULTS: For task (a) using semantic similarity, CliXO
      accurately reconstructs GO (>99% precision, recall) and outperforms other
      approaches (<20% precision, <20% recall). For task (b) using -omics data, CliXO
      outperforms other methods using two -omics datasets and achieves ~30% precision
      and recall using YeastNet v3, similar to an earlier approach (Network Extracted
      Ontology) and better than LocalFitness or standard clustering (20-25% precision,
      recall). CONCLUSION: This study provides algorithmic foundation for building gene
      ontologies by capturing hierarchical and pleiotropic structure embedded in
      biomolecular data.

PMID- 24932004
TI  - Automated detection and tracking of many cells by using 4D live-cell imaging
      data.
AB  - MOTIVATION: Automated fluorescence microscopes produce massive amounts of images
      observing cells, often in four dimensions of space and time. This study addresses
      two tasks of time-lapse imaging analyses; detection and tracking of the many
      imaged cells, and it is especially intended for 4D live-cell imaging of neuronal
      nuclei of Caenorhabditis elegans. The cells of interest appear as slightly
      deformed ellipsoidal forms. They are densely distributed, and move rapidly in a
      series of 3D images. Thus, existing tracking methods often fail because more than
      one tracker will follow the same target or a tracker transits from one to other
      of different targets during rapid moves. RESULTS: The present method begins by
      performing the kernel density estimation in order to convert each 3D image into a
      smooth, continuous function. The cell bodies in the image are assumed to lie in
      the regions near the multiple local maxima of the density function. The tasks of
      detecting and tracking the cells are then addressed with two hill-climbing
      algorithms. The positions of the trackers are initialized by applying the cell
      detection method to an image in the first frame. The tracking method keeps
      attacking them to near the local maxima in each subsequent image. To prevent the
      tracker from following multiple cells, we use a Markov random field (MRF) to
      model the spatial and temporal covariation of the cells and to maximize the image
      forces and the MRF-induced constraint on the trackers. The tracking procedure is
      demonstrated with dynamic 3D images that each contain >100 neurons of C.elegans.
      AVAILABILITY: http://daweb.ism.ac.jp/yoshidalab/crest/ismb2014 SUPPLEMENTARY
      INFORMATION: Supplementary data are available at
      http://daweb.ism.ac.jp/yoshidalab/crest/ismb2014

PMID- 24932005
TI  - Using association rule mining to determine promising secondary phenotyping
      hypotheses.
AB  - MOTIVATION: Large-scale phenotyping projects such as the Sanger Mouse Genetics
      project are ongoing efforts to help identify the influences of genes and their
      modification on phenotypes. Gene-phenotype relations are crucial to the
      improvement of our understanding of human heritable diseases as well as the
      development of drugs. However, given that there are ~: 20 000 genes in higher
      vertebrate genomes and the experimental verification of gene-phenotype relations
      requires a lot of resources, methods are needed that determine good candidates
      for testing. RESULTS: In this study, we applied an association rule mining
      approach to the identification of promising secondary phenotype candidates. The
      predictions rely on a large gene-phenotype annotation set that is used to find
      occurrence patterns of phenotypes. Applying an association rule mining approach,
      we could identify 1967 secondary phenotype hypotheses that cover 244 genes and
      136 phenotypes. Using two automated and one manual evaluation strategies, we
      demonstrate that the secondary phenotype candidates possess biological relevance
      to the genes they are predicted for. From the results we conclude that the
      predicted secondary phenotypes constitute good candidates to be experimentally
      tested and confirmed. AVAILABILITY: The secondary phenotype candidates can be
      browsed through at
      http://www.sanger.ac.uk/resources/databases/phenodigm/gene/secondaryphenotype/lis
      . CONTACT: ao5@sanger.ac.uk or ds5@sanger.ac.uk SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 24932006
TI  - Inductive matrix completion for predicting gene-disease associations.
AB  - MOTIVATION: Most existing methods for predicting causal disease genes rely on
      specific type of evidence, and are therefore limited in terms of applicability.
      More often than not, the type of evidence available for diseases varies-for
      example, we may know linked genes, keywords associated with the disease obtained
      by mining text, or co-occurrence of disease symptoms in patients. Similarly, the
      type of evidence available for genes varies-for example, specific microarray
      probes convey information only for certain sets of genes. In this article, we
      apply a novel matrix-completion method called Inductive Matrix Completion to the
      problem of predicting gene-disease associations; it combines multiple types of
      evidence (features) for diseases and genes to learn latent factors that explain
      the observed gene-disease associations. We construct features from different
      biological sources such as microarray expression data and disease-related textual
      data. A crucial advantage of the method is that it is inductive; it can be
      applied to diseases not seen at training time, unlike traditional matrix
      completion approaches and network-based inference methods that are transductive.
      RESULTS: Comparison with state-of-the-art methods on diseases from the Online
      Mendelian Inheritance in Man (OMIM) database shows that the proposed approach is
      substantially better-it has close to one-in-four chance of recovering a true
      association in the top 100 predictions, compared to the recently proposed
      Catapult method (second best) that has <15% chance. We demonstrate that the
      inductive method is particularly effective for a query disease with no previously
      known gene associations, and for predicting novel genes, i.e. genes that are
      previously not linked to diseases. Thus the method is capable of predicting novel
      genes even for well-characterized diseases. We also validate the novelty of
      predictions by evaluating the method on recently reported OMIM associations and
      on associations recently reported in the literature. AVAILABILITY: Source code
      and datasets can be downloaded from http://bigdata.ices.utexas.edu/project/gene
      disease.

PMID- 24932007
TI  - Robust clinical outcome prediction based on Bayesian analysis of transcriptional
      profiles and prior causal networks.
AB  - MOTIVATION: Understanding and predicting an individual's response in a clinical
      trial is the key to better treatments and cost-: effective medicine. Over the
      coming years, more and more large-scale omics datasets will become available to
      characterize patients with complex and heterogeneous diseases at a molecular
      level. Unfortunately, genetic, phenotypical and environmental variation is much
      higher in a human trial population than currently modeled or measured in most
      animal studies. In our experience, this high variability can lead to failure of
      trained predictors in independent studies and undermines the credibility and
      utility of promising high-dimensional datasets. METHODS: We propose a method that
      utilizes patient-level genome-wide expression data in conjunction with causal
      networks based on prior knowledge. Our approach determines a differential
      expression profile for each patient and uses a Bayesian approach to infer
      corresponding upstream regulators. These regulators and their corresponding
      posterior probabilities of activity are used in a regularized regression
      framework to predict response. RESULTS: We validated our approach using two
      clinically relevant phenotypes, namely acute rejection in kidney transplantation
      and response to Infliximab in ulcerative colitis. To demonstrate pitfalls in
      translating trained predictors across independent trials, we analyze performance
      characteristics of our approach as well as alternative feature sets in the
      regression on two independent datasets for each phenotype. We show that the
      proposed approach is able to successfully incorporate causal prior knowledge to
      give robust performance estimates.

PMID- 24932008
TI  - A combinatorial approach for analyzing intra-tumor heterogeneity from high
      throughput sequencing data.
AB  - MOTIVATION: High-throughput sequencing of tumor samples has shown that most
      tumors exhibit extensive intra-tumor heterogeneity, with multiple subpopulations
      of tumor cells containing different somatic mutations. Recent studies have
      quantified this intra-tumor heterogeneity by clustering mutations into
      subpopulations according to the observed counts of DNA sequencing reads
      containing the variant allele. However, these clustering approaches do not
      consider that the population frequencies of different tumor subpopulations are
      correlated by their shared ancestry in the same population of cells. RESULTS: We
      introduce the binary tree partition (BTP), a novel combinatorial formulation of
      the problem of constructing the subpopulations of tumor cells from the variant
      allele frequencies of somatic mutations. We show that finding a BTP is an NP
      complete problem; derive an approximation algorithm for an optimization version
      of the problem; and present a recursive algorithm to find a BTP with errors in
      the input. We show that the resulting algorithm outperforms existing clustering
      approaches on simulated and real sequencing data. AVAILABILITY AND
      IMPLEMENTATION: Python and MATLAB implementations of our method are available at
      http://compbio.cs.brown.edu/software/ .

PMID- 24932009
TI  - Pareto-optimal phylogenetic tree reconciliation.
AB  - MOTIVATION: Phylogenetic tree reconciliation is a widely used method for
      reconstructing the evolutionary histories of gene families and species, hosts and
      parasites and other dependent pairs of entities. Reconciliation is typically
      performed using maximum parsimony, in which each evolutionary event type is
      assigned a cost and the objective is to find a reconciliation of minimum total
      cost. It is generally understood that reconciliations are sensitive to event
      costs, but little is understood about the relationship between event costs and
      solutions. Moreover, choosing appropriate event costs is a notoriously difficult
      problem. RESULTS: We address this problem by giving an efficient algorithm for
      computing Pareto-optimal sets of reconciliations, thus providing the first
      systematic method for understanding the relationship between event costs and
      reconciliations. This, in turn, results in new techniques for computing event
      support values and, for cophylogenetic analyses, performing robust statistical
      tests. We provide new software tools and demonstrate their use on a number of
      datasets from evolutionary genomic and cophylogenetic studies. AVAILABILITY AND
      IMPLEMENTATION: Our Python tools are freely available at
      www.cs.hmc.edu/~hadas/xscape. .

PMID- 24932010
TI  - Evaluating synteny for improved comparative studies.
AB  - MOTIVATION: Comparative genomics aims to understand the structure and function of
      genomes by translating knowledge gained about some genomes to the object of
      study. Early approaches used pairwise comparisons, but today researchers are
      attempting to leverage the larger potential of multi-way comparisons. Comparative
      genomics relies on the structuring of genomes into syntenic blocks: blocks of
      sequence that exhibit conserved features across the genomes. Syntenic blocs are
      required for complex computations to scale to the billions of nucleotides present
      in many genomes; they enable comparisons across broad ranges of genomes because
      they filter out much of the individual variability; they highlight candidate
      regions for in-depth studies; and they facilitate whole-genome comparisons
      through visualization tools. However, the concept of syntenic block remains
      loosely defined. Tools for the identification of syntenic blocks yield quite
      different results, thereby preventing a systematic assessment of the next steps
      in an analysis. Current tools do not include measurable quality objectives and
      thus cannot be benchmarked against themselves. Comparisons among tools have also
      been neglected-what few results are given use superficial measures unrelated to
      quality or consistency. RESULTS: We present a theoretical model as well as an
      experimental basis for comparing syntenic blocks and thus also for improving or
      designing tools for the identification of syntenic blocks. We illustrate the
      application of the model and the measures by applying them to syntenic blocks
      produced by three different contemporary tools (DRIMM-Synteny, i-ADHoRe and
      Cyntenator) on a dataset of eight yeast genomes. Our findings highlight the need
      for a well founded, systematic approach to the decomposition of genomes into
      syntenic blocks. Our experiments demonstrate widely divergent results among these
      tools, throwing into question the robustness of the basic approach in comparative
      genomics. We have taken the first step towards a formal approach to the
      construction of syntenic blocks by developing a simple quality criterion based on
      sound evolutionary principles.

PMID- 24932012
TI  - Partisans without Constraint: Political Polarization and Trends in American
      Public Opinion.
AB  - Public opinion polarization is here conceived as a process of alignment along
      multiple lines of potential disagreement and measured as growing constraint in
      individuals' preferences. Using NES data from 1972 to 2004, the authors model
      trends in issue partisanship-the correlation of issue attitudes with party
      identification-and issue alignment-the correlation between pairs of issues-and
      find a substantive increase in issue partisanship, but little evidence of issue
      alignment. The findings suggest that opinion changes correspond more to a
      resorting of party labels among voters than to greater constraint on issue
      attitudes: since parties are more polarized, they are now better at sorting
      individuals along ideological lines. Levels of constraint vary across population
      subgroups: strong partisans and wealthier and politically sophisticated voters
      have grown more coherent in their beliefs. The authors discuss the consequences
      of partisan realignment and group sorting on the political process and potential
      deviations from the classic pluralistic account of American politics.

PMID- 24932013
TI  - Legal Cynicism and Parental Appraisals of Adolescent Violence.
AB  - Research suggests that legal cynicism-a cultural frame in which the law is viewed
      as illegitimate and ineffective-encourages violence to maintain personal safety
      when legal recourse is unreliable. But no study has tested the impact of legal
      cynicism on appraisals of violence. Drawing from symbolic interaction theory and
      cultural sociology, we tested whether neighbourhood legal cynicism alters the
      extent to which parents appraise their children's violence as indicative of
      aggressive or impulsive temperaments using data from the Project on Human
      Development in Chicago Neighborhoods. We find that legal cynicism attenuates the
      positive association between adolescent violence and parental assessments of
      aggression and impulsivity. Our study advances the understanding of micro-level
      processes through which prevailing cultural frames in the neighbourhood shape
      violence appraisals.

PMID- 24932011
TI  - Large scale analysis of signal reachability.
AB  - MOTIVATION: Major disorders, such as leukemia, have been shown to alter the
      transcription of genes. Understanding how gene regulation is affected by such
      aberrations is of utmost importance. One promising strategy toward this objective
      is to compute whether signals can reach to the transcription factors through the
      transcription regulatory network (TRN). Due to the uncertainty of the regulatory
      interactions, this is a #P-complete problem and thus solving it for very large
      TRNs remains to be a challenge. RESULTS: We develop a novel and scalable method
      to compute the probability that a signal originating at any given set of source
      genes can arrive at any given set of target genes (i.e., transcription factors)
      when the topology of the underlying signaling network is uncertain. Our method
      tackles this problem for large networks while providing a provably accurate
      result. Our method follows a divide-and-conquer strategy. We break down the given
      network into a sequence of non-overlapping subnetworks such that reachability can
      be computed autonomously and sequentially on each subnetwork. We represent each
      interaction using a small polynomial. The product of these polynomials express
      different scenarios when a signal can or cannot reach to target genes from the
      source genes. We introduce polynomial collapsing operators for each subnetwork.
      These operators reduce the size of the resulting polynomial and thus the
      computational complexity dramatically. We show that our method scales to entire
      human regulatory networks in only seconds, while the existing methods fail beyond
      a few tens of genes and interactions. We demonstrate that our method can
      successfully characterize key reachability characteristics of the entire
      transcriptions regulatory networks of patients affected by eight different
      subtypes of leukemia, as well as those from healthy control samples.
      AVAILABILITY: All the datasets and code used in this article are available at
      bioinformatics.cise.ufl.edu/PReach/scalable.htm.

PMID- 24932014
TI  - Special issue on spine neuromuscular control.

PMID- 24932015
TI  - Whiplash evokes descending muscle recruitment and sympathetic responses
      characteristic of startle.
AB  - Whiplash injuries are the most common injuries following rear-end collisions.
      During a rear-end collision, the human muscle response consists of both a
      postural and a startle response that may exacerbate injury. However, most
      previous studies only assessed the presence of startle using data collected from
      the neck muscles and head/neck kinematics. The startle response also evokes a
      descending pattern of muscle recruitment and changes in autonomic activity. Here
      we examined the recruitment of axial and appendicular muscles along with
      autonomic responses to confirm whether these other features of a startle response
      were present during the first exposure to a whiplash perturbation. Ten subjects
      experienced a single whiplash perturbation while recording electromyography,
      electrocardiogram, and electrodermal responses. All subjects exhibited a
      descending pattern of muscle recruitment, and increasing heart rate and
      electrodermal responses following the collision. Our results provide further
      support that the startle response is a component of the response to whiplash
      collisions. 

PMID- 24932017
TI  - Effect of bracing or surgical treatments on balance control in idiopathic
      scoliosis: three case studies.
AB  - Scoliosis is the most frequent spinal deformity among adolescents. In 80 % of
      cases, it is defined as idiopathic as no individual cause has been identified.
      However, several factors linked to Adolescent Idiopathic Scoliosis (AIS) have
      been identified and are under investigation. One of these factors is neurological
      dysfunction. Increase in body sway has been observed either during or following
      sensory manipulation in AIS patients. It is believed that impairment in sensory
      processing could be related to scoliosis onset. Impairment in sensory processing
      could induce a body schema distortion. The aim of this case series was to
      evaluate if conventional orthopaedic treatments could improve balance control
      thus implying a better body representation. Although, no strong conclusion can be
      drawn from a case series, results suggest that alteration in body representation
      should be investigated in future studies. 

PMID- 24932016
TI  - The use of "stabilization exercises" to affect neuromuscular control in the
      lumbopelvic region: a narrative review.
AB  - It is well-established that the coordination of muscular activity in the
      lumbopelvic region is vital to the generation of mechanical spinal stability.
      Several models illustrating mechanisms by which dysfunctional neuromuscular
      control strategies may serve as a cause and/or effect of low back pain have been
      described in the literature. The term "core stability" is variously used by
      clinicians and researchers, and this variety has led to several rehabilitative
      approaches suggested to affect the neuromuscular control strategies of the
      lumbopelvic region (e.g. "stabilization exercise", "motor control exercise").
      This narrative review will highlight: 1) the ongoing debate in the clinical and
      research communities regarding the terms "core stability" and "stabilization
      exercise", 2) the importance of sub-grouping in identifying those patients most
      likely to benefit from such therapeutic interventions, and 3) two protocols that
      can assist clinicians in this process. 

PMID- 24932018
TI  - The effect of spinal manipulation impulse duration on spine neuromechanical
      responses.
AB  - INTRODUCTION: Spinal manipulation therapy (SMT) is characterized by specific
      kinetic and kinematic parameters that can be modulated. The purpose of this study
      is to investigate fundamental aspects of SMT dose-physiological response relation
      in humans by varying SMT impulse duration. METHODS: Twenty healthy adults were
      subjected to four different SMT force-time profiles delivered by a servo
      controlled linear actuator motor and differing in their impulse duration. EMG
      responses of the left and right thoracic paraspinal muscles (T6 and T8 levels)
      and vertebral displacements of T7 and T8 were evaluated for all SMT phases.
      RESULTS: Significant differences in paraspinal EMG were observed during the
      "Thrust phase" and immediately after ("Post-SMT1") (all T8 ps < 0.01 and T6
      during the thrust ps < 0.05). Sagittal vertebral displacements were similar
      across all conditions (p > 0.05). CONCLUSION: Decreasing SMT impulse duration
      leads to a linear increase in EMG response of thoracic paraspinal during and
      following the SMT thrust.

PMID- 24932019
TI  - Effect of spinal manipulation on the development of history-dependent
      responsiveness of lumbar paraspinal muscle spindles in the cat.
AB  - We determined whether spinal manipulation could prevent and/or reverse the
      decrease and increase in paraspinal muscle spindle responsiveness caused
      respectively by lengthening and shortening histories of the lumbar muscles.
      Single unit spindle activity from multifidus and longissimus muscles was recorded
      in the L6 dorsal root in anesthetized cats. Muscle history was created and spinal
      manipulation delivered (thrust amplitude: 1.0mm, duration: 100ms) using a
      feedback-controlled motor attached to the L6 spinous process. Muscle spindle
      discharge to a fixed vertebral position (static test) and to vertebral movement
      (dynamic test) was evaluated following the lengthening and shortening histories.
      For the static test, changes in muscle spindle responsiveness were significantly
      less when spinal manipulation followed muscle history (p<0.01), but not when
      spinal manipulation preceded it (p>0.05). For the dynamic test, spinal
      manipulation did not significantly affect the history-induced change in muscle
      spindle responsiveness. Spinal manipulation may partially reverse the effects of
      muscle history on muscle spindle signaling of vertebral position. 

PMID- 24932020
TI  - Effect of changing lumbar stiffness by single facet joint dysfunction on the
      responsiveness of lumbar muscle spindles to vertebral movement.
AB  - OBJECTIVE: Individuals experiencing low back pain often present clinically with
      intervertebral joint dysfunction. The purpose of this study was to determine
      whether relative changes in stiffness at a single spinal joint alters neural
      responsiveness of lumbar muscle spindles to either vertebral movement or
      position. METHODS: Muscle spindle discharge was recorded in response to 1mm L6
      ramp and hold movements (0.5mm/s) in the same animal for lumbar laminectomy-only
      (n=23), laminectomy & L5/6 facet screw (n=19), laminectomy & L5/6 facetectomy
      (n=5) conditions. Mean instantaneous frequency (MIF) was calculated for the ramp
      up, hold, ramp-down and post-ramp phases during each joint condition. RESULTS:
      Mean MIFs were not significantly different between the laminectomy-only and the
      other two types of joint dysfunction for the ramp-up, hold, ramp-down, or post
      ramp phases. CONCLUSION: Stiffness changes caused by single facet joint
      dysfunction failed to alter spindle responses during slow 1mm ramp and hold
      movements of the L6 vertebra.

PMID- 24932021
TI  - The origin, and application of somatosensory evoked potentials as a
      neurophysiological technique to investigate neuroplasticity.
AB  - Somatosensory evoked potentionals (SEPs) can be used to elucidate differences in
      cortical activity associated with a spinal manipulation (SM) intervention. The
      purpose of this narrative review is to overview the origin and application of
      SEPs, a neurophysiological technique to investigate neuroplasticity. Summaries
      of: 1) parameters for SEP generation and waveform recording; 2) SEP peak
      nomenclature, interpretation and generators; 3) peaks pertaining to tactile
      information processing (relevant to both chiropractic and other manual
      therapies); 4) utilization and application of SEPs; 5) SEPs concurrent with an
      experimental task and at baseline/control/pretest; 6) SEPs pain studies; and 7)
      SEPs design (pre/post) and neural reorganization/neuroplasticity; and 8) SEPs and
      future chiropractic research are all reviewed. Understanding what SEPs are, and
      their application allows chiropractors, educators, and other manual therapists
      interested in SM to understand the context, and importance of research findings
      from SM studies that involve SEPs. 

PMID- 24932022
TI  - The cervical myodural bridge, a review of literature and clinical implications.
AB  - The role of posterior cervical musculature in sensorimotor control,
      cervicocephalic pain, and stabilization of the spinal cord has been recently
      described. Anatomical soft tissue connections which cross the cervical epidural
      space link suboccipital muscle fascia and dura. These myodural bridges provide
      passive and active anchoring of the spinal cord. They may also be involved in a
      dural tension monitoring system to prevent dural infolding, and maintain patency
      of the spinal cord. Modulation of dural tension may be initiated via a sensory
      reflex to muscular contractile tissues. Unanticipated movements such as
      hyperflexion extension injuries stimulate deep suboccipital muscles and transmit
      tensile forces through the bridge to the cervical dura. Due to its larger cross
      sectional area, the rectus capitis posterior major myodural bridge may exert
      greater mechanical traction on the dura than the rectus capitis posterior minor.
      University ethics committee approval and anatomical donor consent was obtained
      for this study. 

PMID- 24932023
TI  - Real-time force feedback during flexion-distraction procedure for low back pain:
      A pilot study.
AB  - A form of chiropractic procedure known as Cox flexion-distraction is used by
      chiropractors to treat low back pain. Patient lies face down on a specially
      designed table having a stationery thoracic support and a moveable caudal support
      for the legs. The Doctor of Chiropractic (DC) holds a manual contact applying
      forces over the posterior lumbar spine and press down on the moving leg support
      to create traction effects in the lumbar spine. This paper reports on the
      development of real-time feedback on the applied forces during the application of
      the flexion-distraction procedure. In this pilot study we measured the forces
      applied by experienced DCs as well as novice DCs in using this procedure. After a
      brief training with real-time feedback novice DCs have improved on the magnitude
      of the applied forces. This real-time feedback technology is promising to do
      systematic studies in training DCs during the application of this procedure. 

PMID- 24932024
TI  - Microfluidic Channels on Nanopatterned Substrates: Monitoring Protein Binding to
      Lipid Bilayers with Surface-Enhanced Raman Spectroscopy.
AB  - We used Surface Enhanced Raman Spectroscopy (SERS) to detect binding events
      between streptavidin and biotinylated lipid bilayers. The binding events took
      place at the surface between microfluidic channels and anodized aluminum oxide
      (AAO) with the latter serving as substrates. The bilayers were incorporated in
      the substrate pores. It was revealed that non-bound molecules were easily washed
      away and that large suspended cells (Salmonella enterica) are less likely to
      interfere with the monitoring process: when focusing to the lower surface of the
      channel, one may resolve mostly the bound molecules.

PMID- 24932025
TI  - Osteosarcoma: A journey from amputation to limb salvage.

PMID- 24932026
TI  - Multidrug resistant tuberculosis: A challenge in clinical orthopedics.

PMID- 24932028
TI  - Retraction notice.

PMID- 24932027
TI  - Classification, imaging, biopsy and staging of osteosarcoma.
AB  - Osteosarcoma is the most common primary osseous malignancy excluding malignant
      neoplasms of marrow origin (myeloma, lymphoma and leukemia) and accounts for
      approximately 20% of bone cancers. It predominantly affects patients younger than
      20 years and mainly occurs in the long bones of the extremities, the most common
      being the metaphyseal area around the knee. These are classified as primary
      (central or surface) and secondary osteosarcomas arising in preexisting
      conditions. The conventional plain radiograph is the best for probable diagnosis
      as it describes features like sun burst appearance, Codman's triangle, new bone
      formation in soft tissues along with permeative pattern of destruction of the
      bone and other characteristics for specific subtypes of osteosarcomas. X-ray
      chest can detect metastasis in the lungs, but computerized tomography (CT) scan
      of the thorax is more helpful. Magnetic resonance imaging (MRI) of the lesion
      delineates its extent into the soft tissues, the medullary canal, the joint, skip
      lesions and the proximity of the tumor to the neurovascular structures. Tc99 bone
      scan detects the osseous metastases. Positron Emission Tomography (PET) is used
      for metastatic workup and/or local recurrence after resection. The role of
      biochemical markers like alkaline phosphatase and lactate dehydrogenase is
      pertinent for prognosis and treatment response. The biopsy confirms the diagnosis
      and reveals the grade of the tumor. Enneking system for staging malignant
      musculoskeletal tumors and American Joint Committee on Cancer (AJCC) staging
      systems are most commonly used for extremity sarcomas. 

PMID- 24932030
TI  - Surface osteosarcomas: Diagnosis, treatment and outcome.
AB  - Surface osteosarcomas are a rare form of osteosarcomas accounting for around 3-6%
      of all osteosarcomas. Three major groups of surface osteosarcomas are parosteal,
      periosteal and the high grade surface osteosarcomas. Of these, the parosteal
      osteosarcoma is the most common. Parosteal and periosteal osteosarcomas are
      distinct clinical entities and it is important to identify the
      clinicoradiological differences between the two types. Surface osteosarcomas
      occur at a later age as compared to conventional osteosarcomas. The classical
      site is the lower end of the femur followed by the upper end of the tibia and
      upper end of humerus, in that order. The periosteal variant affects the tibia
      more commonly than the parosteal variety. Neo-adjuvant chemotherapy is the
      standard of care for high grade surface osteosarcomas. Parosteal osteosarcomas,
      being low grade lesions, can be treated by upfront wide excision without adjuvant
      systemic therapy. Controversy prevails over the need for chemotherapy in
      periosteal osteosarcomas, which are intermediate grade lesions. 

PMID- 24932029
TI  - Osteosarcoma: Diagnostic dilemmas in histopathology and prognostic factors.
AB  - Osteosarcoma (OS), the commonest malignancy of osteoarticular origin, is a very
      aggressive neoplasm. Divergent histologic differentiation is common in OS; hence
      triple diagnostic approach is essential in all cases. 20% cases are atypical
      owing to lack of concurrence among clinicoradiologic and pathologic features
      necessitating resampling. Recognition of specific anatomic and histologic
      variants is essential in view of better outcome. Traditional prognostic factors
      of OS do stratify patients for short term outcome, but often fail to predict
      their long term outcome. Considering the negligible improvement in the patient
      outcome during the last 20 years, search for novel prognostic factors is in
      progress like ezrin vascular endothelial growth factor, chemokine receptors,
      dysregulation of various micro ribonucleic acid are potentially promising. Their
      utility needs to be validated by long term followup studies before they are
      incorporated in routine clinical practice. 

PMID- 24932031
TI  - The molecular pathogenesis of dedifferentiated chondrosarcoma.
AB  - Dedifferentiated chondrosarcomas are cartilaginous tumors that consist of two
      distinguishable components, a lowgrade chondrosarcoma (chondrogenic) component
      and a highgrade dedifferentiated (anaplastic) component. The tumor cells in both
      components seem to originate from a single precursor, but there are a substantial
      number of genetic alterations in the anaplastic component. The underlying
      mechanism of dedifferentiation is unknown, but cell cycle regulators p16, p53 and
      retinoblastoma appear to have important roles in tumor development and
      dedifferentiation. In this article, molecular pathogenesis of dedifferentiated
      chondrosarcomas is reviewed. 

PMID- 24932032
TI  - Limb salvage surgery for osteosarcoma: Early results in Indian patients.
AB  - BACKGROUND: While limb salvage surgery has long been established as the standard
      of care for osteosarcoma, large studies from Indian centers are few. Given the
      diverse socio economic milieu of our patients, it becomes significant to
      determine the feasibility and outcome of management of osteosarcoma in our
      population. We analyzed the early outcome of limb salvage surgery with
      multimodality treatment of osteosarcoma of the extremity/girdle bones at a
      tertiary North Indian Cancer Centre. MATERIALS AND METHODS: A total of 51 limb
      salvage surgeries performed during the months between November 2008 and November
      2012 were studied. Neoadjuvant/adjuvant chemotherapy was given by the
      pediatric/adult medical oncology teams as applicable. The mean followup was 19.45
      months (range 2-50 months). The oncological outcome was correlated with age, sex,
      size of tumor, stage at presentation, site, histological subtype, type of
      chemotherapy protocol followed and necrosis seen on postoperative examination of
      resected specimen. The functional outcome of the patients was evaluated using the
      musculoskeletal tumor society (MSTS) scoring system. RESULTS: Out of a total of
      37 males and 14 females with an average age of 18.8 years, the 3 year overall
      survival was 66% and 3 year event free survival was 61.8%. In this group of
      patients with a short followup, a better oncological outcome was associated with
      good postoperative tumor necrosis, nonchondroblastic histology and age <14 years.
      The average MSTS score was highest in patients with proximal or distal femur
      prosthesis and the lowest in patients undergoing a knee arthrodesis. CONCLUSION:
      The present study shows oncological and functional outcomes of limb salvage
      combined with chemotherapy in Indian patients with osteosarcoma comparable to
      those in world literature. Larger studies on Indian population with longer
      followup are recommended.

PMID- 24932033
TI  - Outcome of surgical resection of pelvic osteosarcoma.
AB  - BACKGROUND: The aim of the following study is to evaluate the morbidity,
      oncologic results and functional outcome in nonmetastatic patients with primary
      osteosarcoma of the pelvis treated with surgical resection. MATERIALS AND
      METHODS: Twelve cases of nonmetastatic osteosarcoma of pelvis were operated as
      part of their multimodality treatment regime between November 2003 and May 2011.
      There were 5 males and 7 females with a median age of 22 years (range 8-39
      years). Ten patients underwent limb sparing resections while 2 had a hindquarter
      amputation. All 10 cases of limb sparing surgery included resection of the
      acetabulum. A pseudarthrosis was carried out in 7 cases. Extracorporeal radiation
      therapy and reimplantation of the bone followed by fixation with plates was used
      in 1 case and an ischiofemoral arthrodesis was carried out in 2 cases. RESULTS:
      Surgical margins were free in 11 patients. Seven patients had a poor histological
      response to chemotherapy while 4 patients had a good response to chemotherapy. In
      the patient reconstructed with radiated auto bone graft, the histological
      response to chemotherapy could not be assessed. Surgery related complications
      were seen in 8 out of 12 patients (67%). Three of these patients (25%) required
      additional surgical intervention for their complications. All patients were
      available for followup. The median followup of survivors was 56 months (range 24
      102 months). Four patients (33%) developed a local recurrence. At 5 years,
      overall survival was 67%. Patients with a good response to chemotherapy had a
      better overall survival when compared with patients with a poor response to
      chemotherapy. The mean Musculoskeletal Tumor Society functional score was 22
      (range12-27). CONCLUSIONS: Though complex and challenging, surgery provides good
      local control and oncologic outcomes with acceptable function in patients with
      osteosarcoma of the pelvis treated with appropriate surgical resection as part of
      their multimodality treatment.

PMID- 24932034
TI  - Oncological and functional outcome of periosteal osteosarcoma.
AB  - BACKGROUND: Periosteal osteosarcoma is an uncommon variant of osteosarcoma which
      constitutes less than 2% of all osteosarcomas. Whereas adequate surgical excision
      remains the cornerstone of treatment, the role of chemotherapy in this tumor is
      still unclear. Existing literature contains very few single center studies on the
      outcomes for periosteal osteosarcomas and any additional information will help in
      better understanding of these uncommon lesions. This study aims to evaluate the
      oncologic and functional outcomes of treatment of periosteal osteosarcoma treated
      at our institute. MATERIALS AND METHODS: A retrospective analysis of 18 cases of
      periosteal osteosarcoma treated between January 2001 and December 2010 was
      carried out. There were 12 males and 6 females. The mean age at presentation was
      16.3 years (range 5-26 years). Tibia and femur were the most common sites (n =
      8). 16 of 18 patients received chemotherapy, 16 had limb sparing resection, one
      had an amputation and one had rotationplasty. Of the 16 patients with limb
      salvage, conventional wide excision was done in 11 cases. In 5 cases tumor was
      excised with hemicortical excision. Of the 11 cases treated with wide excisions,
      4 patients underwent an osteoarticular resection and in 7 patients a joint
      preserving segmental intercalary resection was done. RESULTS: All patients were
      available for followup. Surgical margins were free in all patients. A good
      response to chemotherapy was seen in 4/11 cases and poor in 6/11 cases. In one
      case the histological response was not discernible due to predominant
      chondromyxoid nature of the tumor. The median followup was 61 months (range: 18
      130 months). There were two local recurrences (11%) at 9 and 18 months
      postsurgery. Pulmonary metastasis subsequently occurred in 4 cases (22%).
      Fourteen patients are currently alive and continuously disease free. Disease free
      survival at 5 years was 77.8% and overall survival (OVS) was 83.3%. Patients
      without marrow involvement had a better OVS at 5 years when compared with
      patients with marrow involvement (90% vs. 75%) (P = 0.23). CONCLUSION: Surgical
      excision remains the mainstay of treatment. Intramedullary involvement may
      suggest aggressive disease biology. The role of chemotherapy is still debatable
      and multicenter studies are needed to provide guidelines.

PMID- 24932035
TI  - High tumor volume and local recurrence following surgery in osteosarcoma: A
      retrospective study.
AB  - BACKGROUND: Osteosarcoma is a high grade malignant, osteoid forming, primary bone
      tumor affecting the metaphysis of long bones. Local recurrence (LR) in
      osteosarcomas is a sinister. Theoretically, a high tumor volume at the time of
      presentation will limit surgical margins, involve vital neurovascular bundles and
      show poor response to chemotherapy thereby causing high rates of amputations (as
      against limb salvage surgery) and should be associated with poor survival rates.
      This study evaluated objectively if high tumor volume is a significant predictor
      of local recurrence (LR) in operated cases of osteosarcomas. MATERIALS AND
      METHODS: Operated cases of osteosarcoma (presenting to the Orthopedic outpatient
      or the Medical Oncology outpatient between January 1, 2004 and January 1, 2011
      were included in the study. Their preoperative clinical data and investigations
      along with the operative notes were traced from the medical/departmental records.
      Details of chemotherapy received in the neo-adjuvant and postoperative periods
      were noted. Besides, all demographic data were also noted. Tumor volume was
      calculated using the available magnetic resonance images using the formula:
      ([pi/6] * length * width * depth). Post data extraction, patients were divided in
      two groups, Groups I (without LR) and Group II (with LR). RESULTS: A total of 95
      cases of biopsy proven osteosarcomas were identified. Of which 64 were male and
      31 females. There were 15 (15.8%) local recurrences. 71% (57/80) patients without
      LR fell in the age group of 10-20 years, while 66% (10/15) patients with LR were
      in the age group of 10-20 years. Limb salvage surgery was done in 81.05% (77/95)
      patients while a total of 18 patients underwent amputation. Of the 80 cases in
      Group I (without LR), 40 (50%) patients had tumor volume >200 c.c., 30 patients
      (37.5%) had tumor volume between 50 and 200 c.c. while only 10 patients had tumor
      volumes <50 c.c. This was in contrast to the tumor volume noted in Group II (with
      LR) of 15 patients where 8 patients had a tumor volume between 50 and 200 c.c.,
      five had bigger tumor volumes of >200 c.c. and only two patients were smaller in
      size, with a tumor volume <50 c.c. The mean tumor volume in the group without LR
      was 406.74 +/- 771.67 c.c. as compared with 195.77 +/- 226.8 c.c. in the group
      with local recurrence. Using Mann-Whitney test, the difference between the two
      groups was found to be statistically insignificant (P = 1.403). CONCLUSIONS: We
      conclude that high tumor volume is not a significant predictor of LR in
      osteosarcomas thus patients with high tumor masses should not be denied limb
      salvage. However, we recommend that the decision on attempting limb salvage
      should not only be based on the tumor volume alone.

PMID- 24932036
TI  - Uncemented allograft-prosthetic composite reconstruction of the proximal femur.
AB  - BACKGROUND: Allograft-prosthetic composite can be divided into three groups names
      cemented, uncemented, and partially cemented. Previous studies have mainly
      reported outcomes in cemented and partially cemented allograft-prosthetic
      composites, but have rarely focused on the uncemented allograft-prosthetic
      composites. The objectives of our study were to describe a surgical technique for
      using proximal femoral uncemented allograft-prosthetic composite and to present
      the radiographic and clinical results. MATERIALS AND METHODS: Twelve patients who
      underwent uncemented allograft-prosthetic composite reconstruction of the
      proximal femur after bone tumor resection were retrospectively evaluated at an
      average followup of 24.0 months. Clinical records and radiographs were evaluated.
      RESULTS: In our series, union occurred in all the patients (100%; range 5-9
      months). Until the most recent followup, there were no cases with infection,
      nonunion of the greater trochanter, junctional bone resorption, dislocation,
      allergic reaction, wear of acetabulum socket, recurrence, and metastasis. But
      there were three periprosthetic fractures which were fixed using cerclage wire
      during surgery. Five cases had bone resorption in and around the greater
      trochanter. The average Musculoskeletal Tumor Society (MSTS) score and Harris hip
      score (HHS) were 26.2 points (range 24-29 points) and 80.6 points (range 66.2
      92.7 points), respectively. CONCLUSIONS: These results showed that uncemented
      allograft-prosthetic composite could promote bone union through compression at
      the host-allograft junction and is a good choice for proximal femoral resection.
      Although this technology has its own merits, long term outcomes are yet not
      validated.

PMID- 24932037
TI  - Tips and tricks of limb salvage: Proximal tibia.
AB  - Due to its anatomical location, the upper end of the tibia poses unique problems
      while attempting limb salvage and appropriate reconstruction. This article
      attempts to highlight a few of the key steps, pearls and pitfalls while
      attempting this challenging procedure. 

PMID- 24932038
TI  - Isolated volar surgical approach for the treatment of perilunate and lunate
      dislocations.
AB  - BACKGROUND: Volar and/or dorsal surgical approaches are used for surgical
      treatment of perilunate and lunate dislocations. There are no accepted approaches
      for treatment in the literature. We evaluated the functional results of isolated
      volar surgical approach for the treatment of perilunate and lunate dislocation
      injuries. MATERIALS AND METHODS: 9 patients (6 male and 3 female patients average
      age 34.5 +/- 3.6 years) diagnosed with perilunate or lunate dislocations between
      January 2000 and January 2009 were involved in the study. The reduction was
      performed through isolated volar surgical approach and K-wire fixation, fracture
      stabilization with volar ligament repair was performed. Range of wrist joint
      motion, fracture healing, carpal stability, grip strength, return to work were
      evaluated and also direct radiographs were taken routinely at each control. The
      scapholunate interval and the scapholunate angle were evaluated radiographically.
      Evaluations of the clinical results were done using the DASH, VAS and Modified
      Mayo Wrist Scores. RESULTS: The physical rehabilitation was started at 6(th)
      week, after the K-wires were removed. The average followup was 18.2 months (range
      12-28 months). At the final followup, the average flexion extension arc was 105.0
      +/- 9.6 degrees  (74.6% of the other side), the average rotation arc was 138.8 +/
      7.8 degrees  (81.5% of the other side) and the average radioulnar arc was 56.1
      +/- 9.9 degrees  (86.4% of the other side). The grip strength was 0.55 bar; 83.2%
      that the uninjured arm. According to the Mayo Modified Wrist score, the
      functional result was excellent in five patients and good in four and the average
      DASH score was 22.8. The scapholunate interval was 2.1 mm and scapholunate angle
      was 51 degrees . CONCLUSION: The clinical and radiological results of the
      isolated volar surgical approach were satisfactory. The dorsal approach was not
      needed for reduction of dislocations during operations. Our results showed that
      an isolated volar approach was adequate.

PMID- 24932039
TI  - In vitro comparison of resistance to implant failure in unstable trochanteric
      fractures fixed with intramedullary single screw versus double screw device.
AB  - BACKGROUND: The purpose of this study was to compare the resistance of
      intramedullary single screw device (Gamma nail) and double screw device proximal
      femoral nail (PFN) in unstable trochanteric fractures in terms of the number of
      cycles sustained, subsidence and implant failure in an axial loading test in
      cadaveric femora. MATERIALS AND METHODS: The study was conducted on 18 dry
      cadaveric femoral specimens, 9 of these were implanted with a Gamma nail and 9
      with PFN. There was no significant difference found in average dual energy X-ray
      absorptiometry value between both groups. The construct was made unstable (AO
      type 31A3.3) by removing a standard sized posteromedial wedge. These were tested
      on a cyclic physiological loading machine at 1 cycle/s with a load of 200 kg. The
      test was observed for 50,000 loading cycles or until implant failure, whichever
      occurred earlier. Peak displacements were measured and analysis was done to
      determine construct stiffness and gap micromotion in axial loading. RESULT: It
      was observed that there was statistically significant difference in terms of
      displacement at the fracture gap and overall construct stiffness of specimens of
      both groups. PFN construct group showed a mean subsidence of 1.02 mm and Gamma
      nail construct group showed mean subsidence of 2.36 mm after cycling. The average
      stiffness of Gamma nail group was 62.8 +/- 8.4 N/mm which was significantly lower
      than average stiffness of the PFN group (80.4 +/- 5.9 N/mm) (P = 0.03). In
      fatigue testing, 1 out of 9 PFN bone construct failed, while 5 of 9 Gamma nail
      bone construct failed. CONCLUSION: When considering micromotion (subsidence) and
      incidence of implant/screw failure, double screw device (PFN) had statistically
      significant lower micromotion across the fracture gap with axial compression and
      lower incidence of implant failure. Hence, double screw device (PFN) construct
      had higher stability compared to single screw device (GN) in an unstable
      trochanteric fracture femur model.

PMID- 24932040
TI  - Autograft reconstructions for bone defects in primary total knee replacement in
      severe varus knees.
AB  - BACKGROUND: Large posteromedial defects encountered in severe varus knees during
      primary total knee arthroplasty can be treated by cementoplasty, structural bone
      grafts or metallic wedges. The option is selected depending upon the size of the
      defect. We studied the outcome of autograft (structural and impaction bone
      grafting) reconstruction of medial tibial bone defects encountered during primary
      total knee replacement in severe varus knees. MATERIALS AND METHODS: Out of 675
      primary varus knees operated, bone defects in proximal tibia were encountered in
      54 knees. Posteromedial defects involving 25-40% of the tibial condyle cut
      surface and measuring more than 5 mm in depth were grafted using a structural
      graft obtained from cut distal femur or proximal tibia in 48 knees. For larger,
      peripheral uncontained vertical defects in six cases, measuring >25 mm in depth
      and involving >40% cut surface of proximal tibial condyle, impaction bone
      grafting with a mesh support was used. RESULTS: Bone grafts incorporated in 54
      knees in 6 months. There was no graft collapse or stress fractures, loosening or
      nonunion. The average followup period was 7.8 years (range 5-10 years). We
      observed an average postoperative increase in the Knee Society Score from 40 to
      90 points. There was improvement in the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scores in terms of pain, stiffness and physical
      function during activities of daily living. CONCLUSION: Bone grafting for defects
      in primary total knee is justified as it is biological, available then and is
      cost effective besides preserving bone stock for future revisions. Structural
      grafts should be used in defects >5 mm deep and involving 25-40% of the cut
      proximal tibial condyle surface. For larger peripheral vertical defects,
      impaction bone grafting contained in a mesh should be done.

PMID- 24932041
TI  - The effects of surgicel and bone wax hemostatic agents on bone healing: An
      experimental study.
AB  - BACKGROUND: The biological effects of hemostatic agends on the physiological
      healing process need to be tested. The aim of this study was to assess the
      effects of oxidized cellulose (surgicel) and bone wax on bone healing in goats'
      feet. MATERIALS AND METHODS: Three congruent circular bone defects were created
      on the lateral aspects of the right and left metacarpal bones of ten goats. One
      defect was left unfilled and acted as a control; the remaining two defects were
      filled with bone wax and surgicel respectively. The 10 animals were divided into
      two groups of 5 animals each, to be sacrificed at the 3(rd) and 5(th) week
      postoperatively. Histological analysis assessing quality of bone formed and micro
      computed tomography (MCT) measuring the quantities of bone volume (BV) and bone
      density (BD) were performed. The results of MCT analysis pertaining to BV and BD
      were statistically analyzed using two-way analysis of variance (ANOVA) and
      posthoc least significant difference tests. RESULTS: Histological analysis at 3
      weeks showed granulation tissue with new bone formation in the control defects,
      active bone formation only at the borders for surgicel filled defects and fibrous
      encapsulation with foreign body reaction in the bone wax filled defects. At 5
      weeks, the control and surgicel filled defects showed greater bone formation;
      however the control defects had the greatest amount of new bone. Bone wax filled
      defects showed very little bone formation. The two-way ANOVA for MCT results
      showed significant differences for BV and BD between the different hemostatic
      agents during the two examination periods. CONCLUSION: Surgicel has superiority
      over bone wax in terms of osseous healing. Bone wax significantly hinders
      osteogenesis and induces inflammation.

PMID- 24932042
TI  - Dermal argyria: Cutaneous manifestation of a megaprosthesis for distal femoral
      osteosarcoma.
AB  - We present a patient with dermal argyria as a cutaneous manifestation of a silver
      coated megaprosthesis used for a distal femoral osteosarcoma. Histological and
      electron microscopic analyses also showed silver deposition in the dermis. 

PMID- 24932043
TI  - Recurrent peripheral embolism following nonunion of the clavicle.
AB  - Vascular complications in closed clavicular fractures are uncommon, with an
      incidence of only 0.4%. Subclavian artery injury can present acutely or can have
      a delayed presentation with arm ischemia. We report the case of an undetected
      subclavian pseudoaneurysm in a patient with a nonunion fracture clavicle who was
      referred with persistent ischemia following attempted brachial embolectomy at
      another center, along with a review of literature to support the hypothesis that
      in addition to repair of the aneurysm, treatment of the psuedarthrosis by
      fixation of the clavicle is essential. 

PMID- 24932044
TI  - Intraarticular osteochondroma of the knee.
AB  - Osteochondromas are usually extra articular and grow away from the joint towards
      the diaphysis. Intraarticular osteochondromas are very rare and often
      misdiagnosed. We report a case of 16-year-old boy who presented with pain and
      clicking sound in the right knee for last 6 months. On examination, click was
      felt at the terminal flexion of the knee. The lateral radiograph of the right
      knee showed a radio opaque shadow at the posterior aspect of the distal end of
      femur, which was further evaluated with an MRI. Arthroscopy showed a hard lesion
      arising from the roof of the intercondylar notch of femur. It was excised
      arthroscopically. Histopathology revealed it to be an osteochondroma. Thus,
      intraarticular osteochondroma of the knee can be considered as a rare cause of
      pain in young patients. 

PMID- 24932045
TI  - Unexplained proximal tibiofibular joint pain after high tibial osteotomy.
AB  - Problems of the proximal tibiofibular joint (pTFj) after high tibial osteotomy
      (HTO) are rare. With this case report, we strive to highlight the importance of
      investigating the pTFj in patients with unexplained knee pain after HTO. A 44
      year old male patient presented with diffuse pain on his left knee 3 years after
      medial opening wedge HTO due to medial compartment overloading in a varus knee.
      Patient described persistent anterior tibial and lateral knee pain. 2 years after
      HTO, patient underwent implant removal but the knee pain persisted. As the reason
      for the persistent pain was not identified, further radiological evaluation was
      done. Single photon emission computerized tomography/computerized tomography
      (SPECT/CT) revealed that there was no increased uptake within the tibiofemoral
      joint, indicating a biologically well performed correction of the varus
      deformity. However, markedly increased tracer uptake was found at the pTFj. On
      the inherent axial CT scans, it was seen that the proximal screws were too long
      and placed within the pTFj. Along with this a severe osteoarthritis of the pTFj
      was identified. The cause of the patient's pain was then confirmed by a CT guided
      infiltration of local anesthetic. An arthrodesis of the pTFj was performed and at
      12 months followup after the arthrodesis the patient was pain free. This case
      highlights how important it is to evaluate the pTFj in patients with unexplained
      pain after HTO. SPECT/CT was helpful in identifying the patient's problem in this
      challenging case. 

PMID- 24932046
TI  - Neonatal Candida arthritis.
AB  - Fungal arthritis is an uncommon yet serious disorder in the newborn. Delay in
      diagnosis and management can lead to significant morbidity. We report our
      experience with management of two such cases. Two preterm neonates with
      multifocal arthritis caused by Candida were studied. Diagnosis was made by
      clinical examination, laboratory investigations, radiological investigations and
      culture. Both were treated by aspiration, arthrotomy and antifungal therapy. One
      patient recovered fully from the infection while the other had growth
      disturbances resulting in limb length inequality at recent followup. Prompt and
      expeditious evacuation of pus from joints and antifungal therapy is imperative
      for treatment. Associated osteomyelitis leads to further difficulty in treatment.

PMID- 24932047
TI  - A biomechanical evaluation of proximal femoral nail antirotation with respect to
      helical blade position in femoral head: A cadaveric study.

PMID- 24932048
TI  - Modified valgus osteotomy of the femoral neck for late presenting femoral neck
      stress fractures in military recruitsw.

PMID- 24932049
TI  - Author's reply.

PMID- 24932050
TI  - Poverty and Material Hardship in Grandparent-Headed Households.
AB  - Using the 2001 Survey of Income and Program Participation, the current study
      examines poverty and material hardship among children living in 3-generation (n =
      486), skipped-generation (n = 238), single-parent (n = 2,076), and 2-parent (n =
      6,061) households. Multinomial and logistic regression models indicated that
      children living in grandparent-headed households experience elevated risk of
      health insecurity (as measured by receipt of public insurance and uninsurance)-a
      disproportionate risk given rates of poverty within those households. Children
      living with single parents did not share this substantial risk. Risk of food and
      housing insecurity did not differ significantly from 2-parent households once
      characteristics of the household and caregivers were taken into account.

PMID- 24932051
TI  - Three-dimensional non-destructive optical evaluation of laser-processing
      performance using optical coherence tomography.
AB  - We demonstrate the use of optical coherence tomography (OCT) as a non-destructive
      diagnostic tool for evaluating laser-processing performance by imaging the
      features of a pit and a rim. A pit formed on a material at different laser
      processing conditions is imaged using both a conventional scanning electron
      microscope (SEM) and OCT. Then using corresponding images, the geometrical
      characteristics of the pit are analyzed and compared. From the results, we could
      verify the feasibility and the potential of the application of OCT to the
      monitoring of the laser-processing performance.

PMID- 24932052
TI  - Novel succinct routes to Quinoxalines and 2-Benzimidazolylquinoxalines via the
      Ugi reaction.
AB  - This communication reveals a unique, user-friendly, concise two-step, one-pot
      protocol for the synthesis of highly substituted quinoxalines. Conducting the Ugi
      reaction with appropriately functionalized classical Ugi reagents with subsequent
      acid treatment of the Ugi adduct affords collections of diversified quinoxalines
      in good to excellent yields. The methodology exploits what may be viewed as a
      'convertible carboxylic acid', which in addition may be captured in an
      intramolecular sense to generate structurally complex 2
      benzimidazolylquinoxalines in a mere two steps.

PMID- 24932053
TI  - Phonetic category recalibration: What are the categories?
AB  - Listeners use lexical or visual context information to recalibrate auditory
      speech perception. After hearing an ambiguous auditory stimulus between /aba/ and
      /ada/ coupled with a clear visual stimulus (e.g., lip closure in /aba/), an
      ambiguous auditory-only stimulus is perceived in line with the previously seen
      visual stimulus. What remains unclear, however, is what exactly listeners are
      recalibrating: phonemes, phone sequences, or acoustic cues. To address this
      question we tested generalization of visually-guided auditory recalibration to 1)
      the same phoneme contrast cued differently (i.e., /aba/-/ada/ vs. /ibi/-/idi/
      where the main cues are formant transitions in the vowels vs. burst and frication
      of the obstruent), 2) a different phoneme contrast cued identically (/aba/-/ada/
      vs. /ama/-/ana/ both cued by formant transitions in the vowels), and 3) the same
      phoneme contrast with the same cues in a different acoustic context (/aba/-/ada/
      vs. (/ubu/-/udu/). Whereas recalibration was robust for all recalibration control
      trials, no generalization was found in any of the experiments. This suggests that
      perceptual recalibration may be more specific than previously thought as it
      appears to be restricted to the phoneme category experienced during exposure as
      well as to the specific manipulated acoustic cues. We suggest that recalibration
      affects context-dependent sub-lexical units.

PMID- 24932054
TI  - Exploring the Relationship Between Social Anxiety and Bulimic Symptoms:
      Mediational Effects of Perfectionism Among Females.
AB  - Previous findings indicate that social anxiety and bulimia co-occur at high
      rates; one mechanism that has been proposed to link these symptom clusters is
      perfectionism. We tested meditational models among 167 female undergraduates in
      which maladaptive evaluative perfectionism concerns (MEPC; i.e., critical self
      evaluative perfectionism) mediated the relationship between social anxiety and
      bulimic symptoms. Results from a first model indicated that MEPC mediated the
      relationship between fear of public scrutiny and bulimia symptoms. This indirect
      effect was significant above and beyond the indirect effects of maladaptive body
      image cognitions and perfectionism specific to pure personal standards. A second
      model was tested with MEPC mediating the relationship between social interaction
      anxiety and bulimia symptoms. Similar results were obtained; however, in this
      model, a significant direct effect remained after partialing out the indirect
      effect of the mediators. Theoretical implications are discussed.

PMID- 24932055
TI  - Quantity and structure of word knowledge across adulthood.
AB  - Cross-sectional and longitudinal data from moderately large samples of healthy
      adults confirmed prior findings of age-related declines in measures of the
      quantity of word knowledge beginning around age 65. Additional analyses were
      carried out to investigate the interrelations of different types of vocabulary
      knowledge at various periods in adulthood. Although the organizational structures
      were similar in adults of different ages, scores on tests with different formats
      had weaker relations to a higher-order vocabulary construct beginning when adults
      were in their 60's. The within-person dispersion among different vocabulary test
      scores was also greater after about 65 years of age. The discovery of
      quantitative decreases in amount of knowledge occurring at about the same age as
      qualitative shifts in the structure of knowledge raises the possibility that the
      two types of changes may be causally linked.

PMID- 24932056
TI  - Scale-Invariant Sparse PCA on High Dimensional Meta-elliptical Data.
AB  - We propose a semiparametric method for conducting scale-invariant sparse
      principal component analysis (PCA) on high dimensional non-Gaussian data.
      Compared with sparse PCA, our method has weaker modeling assumption and is more
      robust to possible data contamination. Theoretically, the proposed method
      achieves a parametric rate of convergence in estimating the parameter of
      interests under a flexible semiparametric distribution family; Computationally,
      the proposed method exploits a rank-based procedure and is as efficient as sparse
      PCA; Empirically, our method outperforms most competing methods on both synthetic
      and real-world datasets.

PMID- 24932057
TI  - Rangeland management and fluvial geomorphology in northern Tanzania.
AB  - Researchers have independently documented the effects of land use on rivers and
      threats to river management institutions, but the relationship between changes in
      institutional context and river condition is not well described. This study
      assesses the connections between resource management institutions, land use, and
      rivers by integrating social science, geospatial analysis, and geomorphology. In
      particular, we measured hydraulic geometry, sediment size distributions, and
      estimated sediment yield for four rivers in northern Tanzania and conducted
      semistructured interviews that assessed corresponding resource management
      institutions. Communities managed rivers through both customary (traditional,
      nonstate) and government institutions, but the differences in the resource
      management policies and practices of the study rivers themselves were fairly
      subtle. Clearer differences were found at broader scales; the four watersheds
      exhibited substantial differences in land cover change and sediment yield
      associated with the location of settlements, roadways, and cultivation.
      Unexpectedly, these recent land use changes did not initiate a geomorphic
      response in rivers. The long history of grazing by domestic and wild ungulates
      may have influenced water and sediment supplies such that river channel
      dimensions are more resistant to changes in land use than other systems or have
      already adjusted to predominant changes in boundary conditions. This would
      suggest that not all rivers will have the anticipated responses to contemporary
      land use changes because of antecedent land use patterns; over long time scales
      (centuries to millennia), the presence of grazers may actually increase the
      ability of rivers to withstand changes in land use. Our findings point to a need
      for further interdisciplinary study of dryland rivers and their shifts between
      system states, especially in areas with a long history of grazing, relatively
      recent changes in land use, and a dynamic social and institutional context.

PMID- 24932058
TI  - Targeted Lung Delivery of Nasally Administered Aerosols.
AB  - Using the nasal route to deliver pharmaceutical aerosols to the lungs has a
      number of advantages including co-administration during non-invasive ventilation.
      The objective of this study was to evaluate the growth and deposition
      characteristics of nasally administered aerosol throughout the conducting airways
      based on delivery with streamlined interfaces implementing two forms of
      controlled condensational growth technology. Characteristic conducting airways
      were considered including a nose-mouth-throat (NMT) geometry, complete upper
      tracheobronchial (TB) model through the third bifurcation (B3), and stochastic
      individual path (SIP) model to the terminal bronchioles (B15). Previously
      developed streamlined nasal cannula interfaces were used for the delivery of
      submicrometer particles using either enhanced condensational growth (ECG) or
      excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD)
      simulations predicted aerosol transport, growth and deposition for a control (4.7
      MUm) and three submicrometer condensational aerosols with budesonide as a model
      insoluble drug. Depositional losses with condensational aerosols in the cannula
      and NMT were less than 5% of the initial dose, which represents an order-of
      magnitude reduction compared to the control. The condensational growth techniques
      increased the TB dose by a factor of 1.1-2.6x, delivered at least 70% of the dose
      to the alveolar region, and produced final aerosol sizes >=2.5 MUm. Compared to
      multiple commercial orally inhaled products, the nose-to-lung delivery approach
      increased dose to the biologically important lower TB region by factors as large
      as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and
      condensational aerosols was highly efficient and targeted deposition to the lower
      TB and alveolar regions.

PMID- 24932059
TI  - Nutrition, Agriculture and the Global Food System in Low and Middle Income
      Countries.
AB  - The entire food value chain and diet of low and middle income countries (LMICs)
      are rapidly shifting. Many of the issues addressed by the nutrition community
      ignore some of the major underlying shifts in purchases of consumer packaged
      foods and beverages. At the same time, the drivers of the food system at the farm
      level might be changing. There is a need for the agriculture and nutrition
      communities to understand these changes and focus on some of their implications
      for health. This rapid growth of the retail sector will change the diets of the
      food insecure as much as that of the food secure across rural and urban LMIC's.
      This short commentary contents that current research, programs and policies are
      ignoring these rapid dynamic shifts.

PMID- 24932060
TI  - Gnawing Pains, Festering Ulcers, and Nightmare Suffering: Selling Leprosy as a
      Humanitarian Cause in the British Empire, c. 1890-1960.
AB  - When British attention was drawn to the issue of leprosy in the Empire,
      humanitarian organisations rose to take on responsibility for the 'fight against
      leprosy'. In an effort to fundraise for a distant cause at a time when hundreds
      of charities competed for the financial support of British citizens, fundraisers
      developed propaganda to set leprosy apart from all other humanitarian causes.
      They drew on leprosy's relationship with Christianity, its debilitating symptoms,
      and the supposed vulnerability of leprosy sufferers in order to mobilise
      Britain's sense of humanitarian, Christian, and patriotic duty. This article
      traces the emergence of leprosy as a popular imperial humanitarian cause in
      modern Britain and analyses the narratives of religion, suffering, and disease
      that they created and employed in order to fuel their growth and sell leprosy as
      a British humanitarian cause.

PMID- 24932061
TI  - Resilience among women with HIV: Impact of silencing the self and socioeconomic
      factors.
AB  - In the U.S., women account for over a quarter of the approximately 50,000 annual
      new HIV diagnoses and face intersecting and ubiquitous adversities including
      gender inequities, sexism, poverty, violence, and limited access to quality
      education and employment. Women are also subjected to prescribed gender roles
      such as silencing their needs in interpersonal relationships, which may lessen
      their ability to be resilient and function adaptively following adversity.
      Previous studies have often highlighted the struggles encountered by women with
      HIV without focusing on their strengths. The present cross-sectional study
      investigated the relationships of silencing the self and socioeconomic factors
      (education, employment, and income) with resilience in a sample of women with
      HIV. The sample consisted of 85 women with HIV, diverse ethnic/racial groups,
      aged 24 - 65 enrolled at the Chicago site of the Women's Interagency HIV Study in
      the midwestern region of the United States. Measures included the Connor-Davidson
      Resilience Scale -10 item and the Silencing the Self Scale (STSS). Participants
      showed high levels of resilience. Women with lower scores on the STSS (lower self
      silencing) reported significantly higher resilience compared to women with higher
      STSS scores. Although employment significantly related to higher resilience,
      silencing the self tended to predict resilience over and above the contributions
      of employment, income, and education. Results suggest that intervention and
      prevention efforts aimed at decreasing silencing the self and increasing
      employment opportunities may improve resilience.

PMID- 24932062
TI  - Cosputtered composition-spread reproducibility established by high-throughput x
      ray fluorescence.
AB  - We describe the characterization of sputtered yttria-zirconia composition spread
      thin films by x-ray fluorescence (XRF). We also discuss our automated analysis of
      the XRF data, which was collected in a high throughput experiment at the Cornell
      High Energy Synchrotron Source. The results indicate that both the composition
      reproducibility of the library deposition and the composition measurements have a
      precision of better than 1 atomic percent.

PMID- 24932063
TI  - Photoluminescence characterization of polythiophene films incorporated with
      highly functional molecules such as metallophthalocyanine.
AB  - The photoluminescence (PL) of conducting polymer polythiophene (PT) films
      incorporated with metallophthalocyanines (PcMs) such as CuPc, MgPc, FePc, Li2Pc,
      and CoPc was studied by PL and time-correlated single photon counting (TCSPC)
      measurements. Polymer films were prepared by electrochemical polymerization and
      PcMs migrated into the polymer films by a diffusion method using acetonitrile or
      toluene as a solvent to dissolve the PcMs. The wavelength of PL emission peaks
      changed significantly depending on the solvent used in the doping process. Using
      acetonitrile, the observed PL emission peaks originated from the Q band, whereas
      they were assigned to the Soret band in the case of toluene. TCSPC measurements
      showed that PL emission took place through a ligand-ligand transition process
      when using acetonitrile because the average lifetimes were comparable and
      independent of the central metal ions for CoPc-, Li2Pc-, and MgPc-doped polymer
      films. Conversely, using toluene, it was found that ligand-ligand emission
      occurred for Li2Pc-, MgPc-, and FePc-doped films. To identify the cause of the
      drastic change in PL emission pattern, x-ray photoelectron spectroscopy
      measurements were obtained. A lower binding energy component appeared in the C 1s
      core-level spectra of acetonitrile-processed PcM-doped PT films, whereas this
      component shifted to higher energy and overlapped with the main peak for toluene
      processed PcM-doped PT films. The lower binding energy component corresponded to
      photoelectrons due to the C atoms in the benzene rings of the ligand. Lower
      binding energy components also appeared in the N 1s core-level spectra of
      acetonitrile-processed PcM-doped PT films, and this component shifted to higher
      energy for toluene-processed PcM-doped PT films. These lower energy components
      were assigned to the core-level peaks due to the N atoms at the meso position
      bridging between pyrrole rings. This suggests that the electron charge at the N
      sites of the meso positions in toluene-processed films was smaller than in
      acetonitrile-processed ones. The changes in energy at benzene C sites and meso N
      sites suggest that the electronic states of the phthalocyanine in the toluene
      processed films were porphyrin-like, so the Soret band became dominant in the PL
      emission spectrum.

PMID- 24932064
TI  - "You Must Know Where You Come From": South African Youths' Perceptions of
      Religion in Time of Social Change.
AB  - This study examined South African youths' perceptions of religion during a period
      of social and economic transition. In-depth interviews were conducted with 55
      Black South African youth (age 18) living in the Johannesburg-Soweto metropolitan
      area. Data were analyzed in a manner consistent with grounded theory methodology
      and structural coding. Beliefs about the function of religion were captured by
      the following themes: provides support, connection to the past, moral compass,
      promotes healthy development, and intersections between African traditional
      practices and Christian beliefs. Themes are discussed and directions for future
      research are presented. In addition, applications of the current research and
      implications for promoting youths' resilience are offered.

PMID- 24932065
TI  - Observed Personality in Childhood: Psychometric and Behavioral Genetic Evidence
      of Two Broad Personality Factors.
AB  - We examined broad dimensions of children's personalities (total n = 1056; age =
      3.5 to 12 years) based on observers' perceptions following a few hours of
      structured interaction. Siblings' behaviors during a two-hour cognitive
      assessment in the home were rated separately by two different observers.
      Exploratory and confirmatory factor analyses clearly revealed a two-factor
      solution in three different samples. There was correspondence between parent
      rated temperament and the observer-rated factors. Cross-sectional analyses
      indicated lower Plasticity among older children and higher Stability among older
      children. Sex differences were negligible. Plasticity and Stability were
      correlated in the .2 to .3 range. Most of the sibling similarity in the
      Plasticity was due to additive genetic influences, whereas most sibling
      similarity in Stability was attributable to shared environmental influences. The
      findings implicate a biometric factor structure to childhood personality that
      fits well with emerging bio-social theories of personality development.

PMID- 24932067
TI  - A stochastic analysis of distance estimation approaches in single molecule
      microscopy - quantifying the resolution limits of photon-limited imaging systems.
AB  - Optical microscopy is an invaluable tool to visualize biological processes at the
      cellular scale. In the recent past, there has been significant interest in
      studying these processes at the single molecule level. An important question that
      arises in single molecule experiments concerns the estimation of the distance of
      separation between two closely spaced molecules. Presently, there exists
      different experimental approaches to estimate the distance between two single
      molecules. However, it is not clear as to which of these approaches provides the
      best accuracy for estimating the distance. Here, we address this problem
      rigorously by using tools of statistical estimation theory. We derive
      formulations of the Fisher information matrix for the underlying estimation
      problem of determining the distance of separation from the acquired data for the
      different approaches. Through the Cramer-Rao inequality, we derive a lower bound
      to the accuracy with which the distance of separation can be estimated. We show
      through Monte-Carlo simulations that the bound can be attained by the maximum
      likelihood estimator. Our analysis shows that the distance estimation problem is
      in fact related to the localization accuracy problem, the latter being a distinct
      problem that deals with how accurately the location of an object can be
      determined. We have carried out a detailed investigation of the relationship
      between the Fisher information matrices of the two problems for the different
      experimental approaches considered here. The paper also addresses the issue of a
      singular Fisher information matrix, which presents a significant complication
      when calculating the Cramer-Rao lower bound. Here, we show how experimental
      design can overcome the singularity. Throughout the paper, we illustrate our
      results by considering a specific image profile that describe the image of a
      single molecule.

PMID- 24932068
TI  - Parental unemployment and children's happiness: A longitudinal study of young
      people's well-being in unemployed households.
AB  - Using a unique longitudinal data of British youths we estimate how adolescents'
      overall happiness is related to parents' exposure to unemployment. Our within
      child estimates suggest that parental job loss when the child was relatively
      young has a positive influence on children's overall happiness. However, this
      positive association became either strongly negative or statistically
      insignificant as the child grew older. The estimated effects of parental job loss
      on children's happiness also appear to be unrelated to its effect on family
      income, parent-child interaction, and children's school experience. Together
      these findings offer new psychological evidence of unemployment effects on
      children's livelihood.

PMID- 24932066
TI  - Measures to Evaluate the Effects of DBS on Speech Production.
AB  - The purpose of this paper is to review and evaluate measures of speech production
      that could be used to document effects of Deep Brain Stimulation (DBS) on speech
      performance, especially in persons with Parkinson disease (PD). A small set of
      evaluative criteria for these measures is presented first, followed by
      consideration of several speech physiology and speech acoustic measures that have
      been studied frequently and reported on in the literature on normal speech
      production, and speech production affected by neuromotor disorders (dysarthria).
      Each measure is reviewed and evaluated against the evaluative criteria. Embedded
      within this review and evaluation is a presentation of new data relating speech
      motions to speech intelligibility measures in speakers with PD, amyotrophic
      lateral sclerosis (ALS), and control speakers (CS). These data are used to
      support the conclusion that at the present time the slope of second formant
      transitions (F2 slope), an acoustic measure, is well suited to make inferences to
      speech motion and to predict speech intelligibility. The use of other measures
      should not be ruled out, however, and we encourage further development of
      evaluative criteria for speech measures designed to probe the effects of DBS or
      any treatment with potential effects on speech production and communication
      skills.

PMID- 24932070
TI  - Dr. Bhatia's legacy in the development of immunohematology research in the
      country.

PMID- 24932069
TI  - With Whom and Where You Play: Preschoolers' Social Context Predicts Peer
      Victimization.
AB  - This short-term longitudinal study assessed the relations between the social
      context of children's play (play-group size, play-group gender composition, and
      play setting) in the fall and peer victimization in the spring for low-income,
      minority, preschool girls and boys. Gender differences in these associations, as
      well as the moderating effect of children's individual problem behavior, were
      considered. Using a multiple-brief observation procedure, preschoolers' (N = 255,
      49% girls) naturally occurring play in each type of social context was recorded
      throughout the fall semester. Observers also rated children's victimization and
      problem behaviors in the fall, and teachers rated children's victimization at the
      end of the school year. Findings suggested that social context variables
      predicted spring victimization above and beyond fall victimization and individual
      levels of problem behavior and that these associations varied for boys and girls.
      The findings signify the importance of the social context on changes in peer
      victimization.

PMID- 24932071
TI  - Transfusion medicine in India: Expanding horizons.

PMID- 24932072
TI  - HPV vaccine, is it really harmful?

PMID- 24932073
TI  - Overview of surgical scar prevention and management.
AB  - Management of incisional scar is intimately connected to stages of wound healing.
      The management of an elective surgery patient begins with a thorough informed
      consent process in which the patient is made aware of personal and clinical
      circumstances that cannot be modified, such as age, ethnicity, and previous
      history of hypertrophic scars. In scar prevention, the single most important
      modifiable factor is wound tension during the proliferative and remodeling
      phases, and this is determined by the choice of incision design. Traditional
      incisions most often follow relaxed skin tension lines, but no such lines exist
      in high surface tension areas. If such incisions are unavoidable, the patient
      must be informed of this ahead of time. The management of a surgical incision
      does not end when the sutures are removed. Surgical scar care should be continued
      for one year. Patient participation is paramount in obtaining the optimal
      outcome. Postoperative visits should screen for signs of scar hypertrophy and has
      a dual purpose of continued patient education and reinforcement of proper care.
      Early intervention is a key to control hyperplastic response. Hypertrophic scars
      that do not improve by 6 months are keloids and should be managed aggressively
      with intralesional steroid injections and alternate modalities. 

PMID- 24932074
TI  - Development and evaluation of Korean version of Quality of Sexual Function (QSF
      K) in healthy Korean women.
AB  - This study was done to develop a Korean version of the Quality of Sexual Function
      (QSF-K) and evaluate the validity and reliability of the QSF-K. The participants
      were 220 women who visited the Center for Uterine Cancer at the National Cancer
      Center in Korea. Participants completed the scale once and then again at a two to
      four week interval. The QSF-K, Female Sexual Function Index (FSFI) and European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 30 (EORTC-QLQ-C30) were used in this study. Receiver operating
      characteristics (ROC) curve, area under the ROC curve (AUC), intraclass
      correlation coefficients (ICC), and Cronbach's alpha were analyzed. In the
      analysis of the reliability, Cronbach's alpha was 0.83 and the ICC was 0.70. The
      validity measured with the AUC of the QSF-K comparing the FSFI and Global
      Health/QOL of the EORTC-QLQ-C30 was 0.717 and 0.728, respectively. Specifically,
      the AUC of the sexual activity level of the QSF-K was 0.838 in the FSFI
      comparison. The AUC of the psycho-somatic QOL of the QSF-K was 0.758 in the
      Global Health/QOL of the EORTC-QLQ-C30 comparison. Approximately half of the
      women (51.8%) had mild complaints/problems. The Korean version of the QSF was
      developed and validated. 

PMID- 24932075
TI  - An early stage evaluation of the Supporting Program for Obstetric Care
      Underserved Areas in Korea.
AB  - "The Supporting Program for Obstetric Care Underserved Areas (SPOU)" provides
      financial aids to rural community (or district) hospitals to reopen prenatal care
      and delivery services for regions without obstetrics and gynecology clinics or
      hospitals. The purpose of this study was to evaluate the early stage effect of
      the SPOU program. The proportion of the number of birth through SPOU was
      calculated by each region. Also survey was conducted to investigate the extent of
      overall satisfaction, elements of dissatisfaction, and suggestions for
      improvement of the program; 209 subjects participated from 7 to 12 December,
      2012. Overall, 20% of pregnant women in Youngdong (71 cases) and Gangjin (106
      cases) used their community (or district) hospitals through the SPOU whereas
      Yecheon (23 cases) was 8%; their satisfaction rates were high. Short distance and
      easy accessibility was the main reason among women choosing community (or
      district) hospital whereas the reasons of not selecting the community (or
      district) hospital were favor of the outside hospital's facility, system, and
      trust in the medical staffs. The SPOU seems to be currently effective at an early
      stage. However, to successfully implement this program, the government should
      make continuous efforts to recruit highly qualified medical staffs and improve
      medical facility and equipment. 

PMID- 24932076
TI  - Improving the reliability of clinical practice guideline appraisals: effects of
      the Korean AGREE II scoring guide.
AB  - The Korean translated Appraisal of Guidelines for Research and Evaluation II
      (Korean AGREE II) instrument was distributed into Korean medical societies in
      2011. However, inter-rater disagreement issues still exist. The Korean AGREE II
      scoring guide was therefore developed to reduce inter-rater differences. This
      study examines the effects of the Korean AGREE II scoring guide to reduce inter
      rater differences. Appraisers were randomly assigned to two groups (Scoring Guide
      group and Non-Scoring Guide group). The Korean AGREE II instrument was provided
      to both groups. However, the scoring guide was offered to Scoring Guide group
      only. Total 14 appraisers were participated and each guideline was assessed by 8
      appraisers. To evaluate the reliability of the Korean AGREE II scoring guide,
      correlation of scores among appraisers and domain-specific intra-class
      correlation (ICC) were compared. Most scores of two groups were comparable.
      Scoring Guide group showed higher reliability at all guidelines. They showed
      higher correlation among appraisers and higher ICC values at almost all domains.
      The scoring guide reduces the inter-rater disagreement and improves the overall
      reliability of the Korean-AGREE II instrument. 

PMID- 24932077
TI  - Clinical features of right-sided infective endocarditis occurring in non-drug
      users.
AB  - Right-sided infective endocarditis (RIE) occurs predominantly in intravenous drug
      users in western countries, and it has a relatively good prognosis. Clinical
      features and prognosis of RIE occurring in non-drug users are not well known. We
      investigated the clinical findings of RIE in non-drug users. We retrospectively
      reviewed 345 cases diagnosed with IE. Cases with RIE or left-sided infective
      endocarditis (LIE) defined by the vegetation site were included and cases having
      no vegetation or both-side vegetation were excluded. Clinical findings and in
      hospital outcome of RIE were compared to those of LIE. Among the 245 cases, 39
      (16%) cases had RIE and 206 (84%) cases had LIE. RIE patients were younger (40 +/
      19 yr vs 50 +/- 18 yr, P=0.004), and had a higher incidence of congenital heart
      disease (CHD) (36% vs 13%, P<0.001) and central venous catheter (CVC) (21% vs 4%,
      P=0.001) compared to LIE patients. A large vegetation was more common in RIE (33%
      vs 9%, P<0.001). Staphylococcus aureus was the most common cause of RIE, while
      Streptococcus viridans were the most common cause of LIE. In-hospital mortality
      and cardiac surgery were not different between the two groups. CHD and use of CVC
      were common in non-drug users with RIE. The short-term clinical outcome of RIE is
      not different from that of LIE.

PMID- 24932078
TI  - Phenotype difference between familial and sporadic ankylosing spondylitis in
      Korean patients.
AB  - Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed.
      We evaluated patients with AS confirmed by the modified New York criteria for
      familial history of AS (one or more first to third degree relatives). The
      clinical characteristics and the recurrence risks (number of AS patients/number
      of familial members) of the familial AS compared to sporadic AS were
      investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported
      that they had a familial history of AS. The recurrence risks in the familial AS
      patients for first, second and third degree family members were 14.5%, 5.2%, and
      4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6 +/- 22.2 vs 35.4 +/
      34.4, P=0.029) and C-reactive protein (CRP) (1.24 +/- 1.7 vs 2.43 +/- 3.3,
      P=0.003) at diagnosis, body mass index (21.9 +/- 2.7 vs 23.7 +/- 3.3, P=0.002)
      and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly
      lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was
      significantly higher in familial AS. In conclusion, Korean familial AS patients
      show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at
      diagnosis and higher presence of HLA-B27.

PMID- 24932079
TI  - Elevated serum homocysteine levels were not correlated with serum uric acid
      levels, but with decreased renal function in gouty patients.
AB  - Hyperhomocysteinemia is one of the important factors of the cardiovascular
      disease, and gout is well known to be associated with cardiovascular disease.
      There are a few reports on the serum homocysteine (Hcy) levels in patients with
      gout, however, the results showed discrepancies. In this study, we measured Hcy
      levels in patients with gout and examined factors associated with the levels of
      serum Hcy. Ninety-one male patients with gout and 97 age-matched healthy male
      controls were enrolled in the study. Serum uric acid levels were not
      significantly different between gout and healthy control groups. However, serum
      Hcy levels were significantly higher in patients with gout compared to controls
      (13.96 +/- 4.05 uM/L vs 12.67 +/- 3.52 uM/L, P=0.035). In gout group, patients
      with 1-2 stages of chronic kidney disease (CKD) had significantly lower serum Hcy
      than those with 3-5 stages of CKD (13.15 +/- 3.46 uM/L vs 17.45 +/- 4.68 uM/L,
      P<0.001). Multivariate linear analysis revealed an inverse association between
      serum Hcy and estimated glomerular filtration rate (eGFR) (beta=-0.107, P<0.001).
      In conclusion, serum Hcy was elevated in male patients with gout.
      Hyperhomocysteinemia was not correlated with serum uric acid, but it was
      inversely associated with impaired renal function.

PMID- 24932080
TI  - The effect of body mass index on survival in advanced epithelial ovarian cancer.
AB  - Controversy remains regarding the effect of obesity on the survival of patients
      with ovarian cancer in Asia. This study examined the impact of obesity on the
      survival outcomes in advanced epithelial ovarian cancer (EOC) using Asian body
      mass index (BMI) criteria. The medical records of patients undergoing surgery for
      advanced (stage III and IV) EOC were reviewed. Statistical analyses included
      ANOVA, chi-square test, Kaplan-Meier survival and Cox regression analysis. Among
      all 236 patients, there were no differences in overall survival according to BMI
      except in underweight patients. In a multivariate Cox analysis, surgical
      optimality and underweight status were independent and significant prognostic
      factors for survival (HR, 2.302; 95% CI, 1.326-3.995; P=0.003 and HR, 8.622; 95%
      CI, 1.871-39.737; P = 0.006, respectively). In the subgroup of serous histology
      and optimal surgery, overweight and obese I patients showed better survival than
      normal weight patients (P = 0.012). We found that underweight BMI and surgical
      optimality are independent risk factors for the survival of patients with
      advanced ovarian cancer. High BMI groups (overweight, obese I and II) are not
      associated with the survival of advanced EOC patient. However, in the subgroup of
      EOC patients with serous histology and after optimal operation, overweight and
      obese I group patients show better survival than the normal weight group
      patients. 

PMID- 24932081
TI  - Determinants of brachial-ankle pulse wave velocity and carotid-femoral pulse wave
      velocity in healthy Koreans.
AB  - The aim of this study was to determine the normal value of brachial-ankle pulse
      wave velocity (baPWV) and carotid-femoral pulse wave velocity (cfPWV) according
      to age group, gender, and the presence of cardiovascular risk factors in healthy
      Koreans, and to investigate the association between PWV and risk factors such as
      prehypertension, dyslipidemia, smoking, and obesity. We measured an arterial
      stiffness in 110 normal subjects who were 20 to 69 yr-old with no evidence of
      cardiovascular disease, cerebrovascular accident or diabetes mellitus. The mean
      values of baPWV and cfPWV were 12.6 (+/- 2.27) m/sec (13.1 +/- 1.85 in men, 12.1
      +/- 2.51 in women; P=0.019) and 8.70 (+/- 1.99) m/sec (9.34 +/- 2.13 in men, 8.15
      +/- 1.69 in women; P=0.001), respectively. The distribution of baPWV (P<0.001)
      and cfPWV (P=0.006) by age group and gender showed an increase in the mean value
      with age. Men had higher baPWV and cfPWV than women (P<0.001). There was a
      difference in baPWV and cfPWV by age group on prehypertension, dyslipidemia,
      current smoking, or obesity (P<0.001). In multiple linear regression, age and
      prehypertension were highly associated with baPWV and cfPWV after adjustment for
      confounding factors (P<0.001). The present study showed that baPWV and cfPWV are
      associated with age, gender, and prehypertension in healthy Koreans.

PMID- 24932082
TI  - Efficacy of hemocontrol biofeedback system in intradialytic hypotension-prone
      hemodialysis patients.
AB  - We conducted a study to determine whether the hemocontrol biofeedback system
      (HBS) can improve intradialytic hypotension (IDH) in hypotension-prone
      hemodialysis (HD) patients compared with conventional HD. In this multicenter
      prospective crossover study, 60 hypotension-prone patients were serially treated
      by conventional HD for 8 weeks (period A), by HD with hemoscan blood volume
      monitoring for 2 weeks (period B0), and by HBS HD for 8 weeks (period B1). The
      number of sessions complicated by symptomatic IDH during 24 HD sessions (14.9 +/-
      5.8 sessions, 62.1% in period A vs 9.2 +/- 7.2 sessions, 38.4% in period B1,
      P<0.001) and the number of IDH-related nursing interventions in a session (0.96
      +/- 0.66 in period A vs 0.56 +/- 0.54 in period B1, P<0.001) significantly
      decreased in period B1 than in period A. Recovery time from fatigue after
      dialysis was significantly shorter in period B1 than in period A. The patients
      with higher post-dialysis blood pressure, lower difference between pre- and post
      dialysis blood pressure, less frequent IDH, and higher pre- and post-dialysis
      body weight in period A responded better to HBS in period B1 in regard to the
      reduction of IDH. In conclusion, HBS may improve the patient tolerability to HD
      by reducing the IDH frequency and promoting faster recovery from fatigue after
      dialysis.

PMID- 24932083
TI  - The effectiveness of recombinant human thyroid-stimulating hormone versus thyroid
      hormone withdrawal prior to radioiodine remnant ablation in thyroid cancer: a
      meta-analysis of randomized controlled trials.
AB  - We evaluated the efficacy of recombinant human thyroid-stimulating hormone
      (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant
      ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the
      Cochrane Library, and SCOPUS was performed. Randomized controlled trials that
      compared ablation success between rhTSH and THW at 6 to 12 months following RRA
      were included in this study. Six trials with a total of 1,660 patients were
      included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1
      ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1
      ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW
      were similar. There were no significant differences when ablation success was
      defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL
      plus imaging modality (RR 1.02; 0.95-1.09). When a negative (131)I-whole body
      scan was used solely as the definition of ablation success, the effects of rhTSH
      and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore,
      ablation success rates are comparable when RRA is prepared by either rhTSH or
      THW. 

PMID- 24932084
TI  - Diffuse metastasis to the thyroid: unique ultrasonographic finding and clinical
      correlation.
AB  - Cases of metastases to the thyroid gland seem to be increasing in recent years.
      The clinical and ultrasonographic findings of diffuse metastases have been
      sparsely reported. Thirteen cases of diffuse metastases to the thyroid gland were
      documented by thyroid ultrasonography-guided fine needle aspiration cytology
      between 2004 and 2013. We retrospectively reviewed the patients with diffuse
      thyroid metastases. The most common primary site was the lung (n=9), followed by
      unknown origin cancers (n=2), cholangiocarcinoma (n=1), and penile cancer (n=1).
      Eleven patients were incidentally found to have thyroid metastases via
      surveillance or staging FDG-PET. Other 2 patients were diagnosed during work-up
      for hypothyroidism and palpable cervical lymph nodes. On ultrasonography, the
      echogenicity of the enlarged thyroid gland was heterogeneously hypoechoic or
      isoechoic, and reticular pattern internal hypoechoic lines were observed without
      increased vascularity found by power Doppler ultrasonography (3 right lobe, 2
      left lobe, and 8 both lobes). In the 8 patients who had involvement of both
      lobes, 3 had hypothyroidism. In conclusion, ultrasonographic finding of diffuse
      metastasis is a diffusely enlarged heterogeneous thyroid with reticular pattern
      internal hypoechoic lines. Thyroid function testing should be performed in all
      patients with diffuse thyroid metastases, especially those with bilateral lobe
      involvement. 

PMID- 24932085
TI  - Prevalence of chronic sputum and associated factors in Korean adults.
AB  - Chronic sputum is a troublesome symptom in many respiratory diseases. The
      prevalence of chronic sputum varies from 1.2% to 13% according to the country.
      The purpose of this study was to estimate the prevalence of chronic sputum and to
      find its associated factors in a general Korean population. We analyzed the data
      of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A
      total number of 6,783 subjects aged 40 yr or more were enrolled in this study
      with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was
      6.3% (n=430). Significant risk factors for chronic sputum by multivariate
      analysis were: age (>= 70 yr) (odds ratio [OR], 1.954; 95% confidence interval
      [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic
      obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and
      tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of
      chronic sputum in Korea was in the intermediate range compared with other
      countries. Smoking is a preventable risk factor identified in this study, and
      major respiratory diseases, such as COPD and tuberculosis, should be considered
      in subjects with chronic sputum.

PMID- 24932086
TI  - A pilot prospective study of the relationship among cognitive factors, shame, and
      guilt proneness on posttraumatic stress disorder symptoms in female victims of
      sexual violence.
AB  - This study prospectively examined the relationships among cognitive factors and
      severity of Posttraumatic stress disorder (PTSD) symptoms in female victims of
      sexual violence. Thirty-eight victims of sexual violence recruited from Center
      for Women Victims of Sexual and Domestic Violence at Ajou University Hospital.
      Cognitive factors and PTSD symptom were assessed within 4 months of sexual
      violence and 25 victims were followed-up 1 month after initial assessment.
      Repeated-measured ANOVA revealed that PTSD incidence and severity decreased over
      the month (F [1, 21]=6.61). Particularly, avoidant symptoms might decrease
      earlier than other PTSD symptoms (F [1, 21]=5.92). This study also showed the
      significant relationship between early negative trauma-related thoughts and
      subsequent PTSD severity. Shame and guilt proneness had significant cross
      sectional correlations with PTSD severity, but did not show associations when
      depression severity is controlled. Our results suggest that avoidant symptoms
      might decrease earlier than other PTSD symptoms during the acute phase and that
      cognitive appraisals concerning the dangerousness of the world seem to play an
      important role in the maintenance of PTSD (r=0.499, P<0.05). 

PMID- 24932087
TI  - The Korean version of the trauma symptom checklist for children: psychometric
      properties and the connection to trauma among Korean children and adolescents.
AB  - The purpose of the present study was to develop a Korean version of the trauma
      symptom checklist for children (TSCC) and to examine its reliability and validity
      for screening posttraumatic stress symptoms. A normative group of 405 children
      and adolescents aged 8 to 16 yr participated in the study. A test-retest
      procedure was conducted with 76 participants from the normative group after 4
      weeks. In the traumatized group, 73 children and adolescents of the same age from
      the Child Sexual Abuse Treatment Center were included. Good internal consistency
      (Cronbach's alpha) for the total scale (0.95, ranging 0.79-0.85 on the clinical
      scales) and test-retest reliability for the total scale (r=0.91, ranging 0.71
      0.87 on the clinical scales) were found. Confirmatory 6-factor analysis explained
      51.1% of the variance. Other measures such as concurrent or discriminative
      validity were also shown to be satisfactory. In conclusion, the Korean version of
      TSCC has been shown to be a screening instrument with satisfactory psychometric
      qualities that is capable of identifying trauma symptoms among children and
      adolescents who have self-reported experiencing trauma or for whom clinicians
      have identified traumatic experiences. 

PMID- 24932088
TI  - Evaluation of stem cell components in retrocorneal membranes.
AB  - The purpose of this study was to elucidate the origin and cellular composition of
      retrocorneal membranes (RCMs) associated with chemical burns using
      immunohistochemical staining for primitive cell markers. Six cases of RCMs were
      collected during penetrating keratoplasty. We examined RCMs with hematoxylin and
      eosin (H&E), periodic acid-Schiff (PAS) staining and immunohistochemical analysis
      using monoclonal antibodies against hematopoietic stem cells (CD34, CD133, c
      kit), mesenchymal stem cells (beta-1-integrin, TGF-beta, vimentin, hSTRO-1),
      fibroblasts (FGF-beta, alpha-smooth muscle actin), and corneal endothelial cells
      (type IV collagen, CD133, VEGF, VEGFR1). Histologic analysis of RCMs revealed an
      organized assembly of spindle-shaped cells, pigment-laden cells, and thin
      collagenous matrix structures. RCMs were positive for markers of mesenchymal stem
      cells including beta-1-integrin, TGF-beta, vimentin, and hSTRO-1. Fibroblast
      markers were also positive, including FGF-beta and alpha-smooth muscle actin
      (SMA). In contrast, immunohistochemical staining was negative for hematopoietic
      stem cell markers including CD34, CD133 and c-kit as well as corneal endothelial
      cell markers such as type IV collagen, CD133 except VEGF and VEGFR1. Pigment
      laden cells did not stain with any antibodies. The results of this study suggest
      that RCMs consist of a thin collagen matrix and fibroblast-like cells and may be
      a possible neogenetic structure produced from a lineage of bone marrow-derived
      mesenchymal stem cells.

PMID- 24932089
TI  - Epidemiology of hip replacements in Korea from 2007 to 2011.
AB  - We analyzed national data collected by the Health Insurance Review and Assessment
      Service in Korea from 2007 to 2011; 1) to document procedural numbers and
      procedural rate of bipolar hemiarthroplasty (BH), primary and revision total hip
      arthroplasties (THAs), 2) to stratify the prevalence of each procedure by age,
      gender, and hospital type, and quantified, 3) to estimate the revision burden and
      evaluate whether the burden is changed over time. Our final study population
      included 60,230 BHs, 40,760 primary THAs, and 10,341 revision THAs. From 2007 to
      2011, both the number and the rate of BHs, primary THAs increased steadily,
      whereas there was no significant change in revision THAs. Over the 5 yr, the rate
      of BHs and primary THAs per 100,000 persons significantly increased by 33.2% and
      21.4%, respectively. The number of revision THAs was consistent over time. The
      overall annual revision burden for THA decreased from 22.1% in 2007 to 18.9% in
      2011. In contrast to western data, there were no changes in the number and rate
      of revision THAs, and the rates of primary and revision THAs were higher for men
      than those for women. Although 5 yr is a short time to determine a change in the
      revision burden, there have been significant decreases in some age groups. 

PMID- 24932090
TI  - The influence of vertebral fracture on the functional disability of patients with
      rheumatoid arthritis.
AB  - The aim of the present study was to identify the influence of vertebral fracture
      (VF) on the functional disability in patients with rheumatoid arthritis (RA).
      This study consecutively enrolled 100 female patients aged 50 yr or older with
      RA. All participants underwent lateral imaging of the thoracolumbar spine by
      simple radiography to identify any VFs. They also completed questionnaires via
      interview regarding demographics, medical history, and disease outcomes including
      functional disability. We used univariate analysis to evaluate associations
      between functional disability and VF, and made multivariate logistic regression
      models to test independent effect of the presence of VF, the number of VFs, and
      the severity of VF on functional disability. Among the 100 RA patients, 47 had at
      least one VF, but 34 of them were asymptomatic that they had experienced a
      fracture. The multiple VFs >= 3 (OR, 8.95; 95% CI, 1.77-44.15, P = 0.01) and
      moderate or severe VF (OR, 3.38; 95% CI, 1.26-9.04, P = 0.02) were related to
      disability in univariate analysis. The multiple VFs >= 3 (OR, 6.13; 95% CI, 1.02
      36.94, P = 0.048) was associated with functional disability of RA patients after
      adjusting various confounders and it was mainly in walking and arising. The VF
      might be an important factor which affects functional disability in RA patients. 

PMID- 24932091
TI  - Clinical demographics and outcomes in mechanically ventilated patients in Korean
      intensive care units.
AB  - Knowledge of clinical demographics and outcomes of mechanically ventilated
      patients is important but there are few prospectively collected data in Korea.
      The objective of the present study was to describe the current status of
      mechanically ventilated patients in Korea as of 2010. We analyzed the data of
      Korean patients (275 patients in 12 Korean intensive care units [ICU])
      participating in a multinational prospective cohort study on mechanical
      ventilation. The most common indication for mechanical ventilation was pneumonia
      (23%). Pressure-limited ventilation modes were preferred over volume-cycled
      ventilation modes. Non-invasive positive pressure ventilation was used in only
      seven (2%) patients as the initial ventilatory support. Median duration of
      mechanical ventilation was 7 days and ICU mortality was 36%. The multiple
      logistic regression model revealed that the Simplified Acute Physiology Score II
      (SAPS II) score at ICU admission (odds ratio [OR], 1.034; 95% confidence interval
      [CI], 1.001-1.036; P=0.033), peak pressure (OR, 1.054; 95% CI, 1.016-1.095;
      P=0.006), and the number of failed organs (OR, 2.132; 95% CI, 1.634-2.781;
      P<0.001) were independently associated with ICU mortality. This study provides a
      snapshot of current practice of mechanical ventilation in Korea. 

PMID- 24932092
TI  - Percutaneous retrieval and redeployment of an atrial septal occluder under three
      dimensional transesophageal echocardiographic guidance: a case report.
AB  - Percutaneous device closure for secundum atrial septal defects (ASDs) has been
      performed commonly and safely with high success rates. However, it is still
      challenging to close ASDs that are surrounded with deficient or hypermobile rims
      and could be compromised with an unexpected migration of device. We report a case
      of percutaneous Amplazter Septal Occluder (ASO; St. Jude Medical Inc., St. Paul,
      Minnesota, USA) device closure for an ASD with a thin and floppy interatrial
      septum, which immediately migrated into the right atrium and was not pulled back
      into the delivery sheath. To our knowledge, this is the first report on a
      successful percutaneous retrieval and redeployment of the device in such a
      situation, preventing any vascular injury or unplanned emergency open heart
      surgery. 

PMID- 24932093
TI  - Lemmel's syndrome, an unusual cause of abdominal pain and jaundice by impacted
      intradiverticular enterolith: case report.
AB  - Duodenal diverticula are detected in up to 27% of patients undergoing upper
      gastrointestinal tract evaluation with periampullary diverticula (PAD) being the
      most common type. Although PAD usually do not cause symptoms, it can serve as a
      source of obstructive jaundice even when choledocholithiasis or tumor is not
      present. This duodenal diverticulum obstructive jaundice syndrome is called
      Lemmel's syndrome. An 81-yr-old woman came to the emergency room with obstructive
      jaundice and cholangitis. Abdominal CT scan revealed stony opacity on distal CBD
      with CBD dilatation. ERCP was performed to remove the stone. However, the stone
      was not located in the CBD but rather inside the PAD. After removal of the
      enterolith within the PAD, all her symptoms resolved. Recognition of this
      condition is important since misdiagnosis could lead to mismanagement and
      therapeutic delay. Lemmel's syndrome should always be included as one of the
      differential diagnosis of obstructive jaundice when PAD are present.

PMID- 24932094
TI  - Transient complete atrioventricular block in a preterm neonate with congenital
      myotonic dystrophy: case report.
AB  - Congenital myotonic dystrophy (CMD) is an inherited neuromuscular disorder with
      cardiac rhythm abnormalities that may occur as a child grows. No report has
      described complete atrioventricular (AV) block detected in a neonate with CMD. We
      report a floppy infant of 31(+4) weeks gestation with complete AV block at birth,
      who was diagnosed with CMD by Southern analysis. She recovered from complete AV
      block 32 hr after temporary transcutaneous pacing was applied. To the best our
      knowledge, this is the first recorded case of a complete AV block accompanied by
      CMD during the neonatal period. When a newborn has a complete AV block, the
      physician should consider the possibility of the CMD and conduct a careful
      physical examination. 

PMID- 24932095
TI  - Sexual Reproductive Biology of a Colonial Rotifer Sinantherina socialis
      (Rotifera: Monogononta): Do mating strategies vary between colonial and solitary
      rotifer species?
AB  - In many aquatic invertebrates including monogonont rotifers, sex provides genetic
      variation and dormant stages that allows dispersal in time and space. While the
      reproductive biology of some solitary monogonont rotifer species is known, little
      is known concerning mating behaviors in colonial rotifers. Coloniality poses
      unique challenges to the typical mating behavior of solitary rotifers. For
      instance, most species engage in circling behavior, where the male swims in close
      proximity to the female. In colonial forms, access to a particular female may be
      hindered by nearby colony mates. Here we provide descriptions of (1) male
      morphology, (2) mating behavior, and (3) types of eggs of the widespread colonial
      rotifer Sinantherina socialis, and discuss modifications in mating strategies as
      a consequence of coloniality. Two important differences from mating patterns
      documented in solitary rotifers were found in S. socialis. First, duration of
      circling phase of mating is protracted for males encountering small colonies of
      females as compared to solitary females. Males encountering single females
      removed from their colonies behave similarly to those of solitary species.
      Second, duration of copulation in S. socialis is the shortest reported for any
      rotifer species. Endogamy might occur in this species as sons copulate with their
      sisters and mothers, at least under laboratory conditions. Examples of behaviour
      in linked video clips.

PMID- 24932096
TI  - Turbulent dispersion via fan-generated flows.
AB  - Turbulent dispersion of passive scalar quantities has been extensively studied in
      wind tunnel settings, where the flow is carefully conditioned using flow
      straighteners and grids. Much less is known about turbulent dispersion in the
      "unconditioned" flows generated by fans that are ubiquitous in indoor
      environments, despite the importance of these flows to pathogen and contaminant
      transport. Here, we demonstrate that a point source of scalars released into an
      airflow generated by an axial fan yields a plume whose width is invariant with
      respect to the fan speed. The results point toward a useful simplification in
      modeling of disease and pollution spread via fan-generated flows.

PMID- 24932097
TI  - Designing a Wearable Computer for Lifestyle Evaluation.
AB  - A wearable computer, called eButton, has been developed for evaluation of the
      human lifestyle. This ARM-based device acquires multimodal data from a camera
      module, a motion sensor, an orientation sensor, a light sensor and a GPS
      receiver. Its performance has been tested both in our laboratory and by human
      subjects in free-living conditions. Our results indicate that eButton can record
      real-world data reliably, providing a powerful tool for the evaluation of
      lifestyle for a broad range of applications.

PMID- 24932098
TI  - Modeling the altered expression levels of genes on signaling pathways in tumors
      as causal bayesian networks.
AB  - This paper concerns a study indicating that the expression levels of genes in
      signaling pathways can be modeled using a causal Bayesian network (BN) that is
      altered in tumorous tissue. These results open up promising areas of future
      research that can help identify driver genes and therapeutic targets. So, it is
      most appropriate for the cancer informatics community. Our central hypothesis is
      that the expression levels of genes that code for proteins on a signal
      transduction network (STP) are causally related and that this causal structure is
      altered when the STP is involved in cancer. To test this hypothesis, we analyzed
      5 STPs associated with breast cancer, 7 STPs associated with other cancers, and
      10 randomly chosen pathways, using a breast cancer gene expression level dataset
      containing 529 cases and 61 controls. We identified all the genes related to each
      of the 22 pathways and developed separate gene expression datasets for each
      pathway. We obtained significant results indicating that the causal structure of
      the expression levels of genes coding for proteins on STPs, which are believed to
      be implicated in both breast cancer and in all cancers, is more altered in the
      cases relative to the controls than the causal structure of the randomly chosen
      pathways. 

PMID- 24932099
TI  - Folate receptor alpha, mesothelin and megakaryocyte potentiating factor as
      potential serum markers of chronic kidney disease.
AB  - Renal disease is the eighth leading cause of death in the United States. Early
      diagnosis is usually based on the detection of proteinuria or elevated serum
      creatinine, a relatively poor biomarker that does not accurately predict renal
      disease progression. As a result, more predictive biomarkers of renal function
      are sought. We present preliminary data on three protein biomarkers, folate
      receptor alpha (FRA), mesothelin (MSLN), and megakaryocyte potentiating factor
      (MPF), currently being pursued for applications in oncology diagnostics, and
      evaluate serum and urine levels in subjects with renal disease. Compared to
      healthy subjects, a significant (P < 0.0001) increase in all three biomarkers in
      both serum and urine of subjects with renal disease was demonstrated. Further,
      serum levels of these three protein biomarkers increased with increasing stage of
      disease suggesting their potential value in predicting progression in subjects
      with renal disease and raising caution in interpretation of data in oncology
      applications. 

PMID- 24932100
TI  - Kinetic Study of the Alkaline Degradation of Oseltamivir Phosphate and
      Valacyclovir Hydrochloride using Validated Stability Indicating HPLC.
AB  - Aqueous alkaline degradation was performed for oseltamivir phosphate (OP) and
      valacyclovir hydrochloride (VA). Isocratic stability indicating the use of high
      performance liquid chromatography (HPLC) was presented for each drug in the
      presence of its degradation product. The separations were performed using the
      Nucleosil ODS column and a mobile phase consisting of phosphate buffer (pH = 7),
      acetonitrile, and methanol 50:25:25 (v/v/v) for OP. For VA separation, a
      Nucleosil CN column using phosphate buffer (pH = 7) and methanol 85:15 (v/v) was
      used as a mobile phase. Ultraviolet detection at 210 nm and 254 nm was used for
      OP and VA, respectively. The method showed high sensitivity concerning linearity,
      accuracy, and precision over the range 1-250 MUg mL(-1) for both drugs. The
      proposed method was used to determine the drug in its pharmaceutical formulation
      and to investigate the degradation kinetics of each drug's alkaline-stressed
      samples. The reactions were found to follow a first-order reaction. The
      activation energy could also be estimated. International Conference on
      Harmonisation guidelines were adopted for method validation. 

PMID- 24932102
TI  - Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is
      Associated with Sickle Cell Disease in Africa.
AB  - Sickle cell disease shows marked variability in severity and pathophysiology
      among individuals, probably linked to differential expression of various adhesion
      molecules. In this study, we investigated the differential distribution, genomic
      diversity and haplotype frequency of endothelial nitric oxide synthase (eNOS) and
      endothelin-1 (ET-1) polymorphisms, recently implicated as important in
      modification of disease severity. One hundred and forty five sickle cell disease
      patients (HbSS) and 244 adult and pediatric controls, without sickle cell disease
      (HbAA), were recruited from Mali. Genotypic analysis of the functionally
      significant eNOS variants (T786C, G894T and intron 4) and endothelin-1 (G5665T)
      was carried out with a polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assay. Our results show that the wild type alleles are
      the most frequent for all eNOS variants between cases and controls. Allelic and
      genotypic frequencies of eNOS polymorphic groups are not significantly different
      between cases and controls (P > 0.05). In addition, there is no association
      between eNOS variants and sickle cell disease, contrary to published reports. On
      the other hand, we report that endothelin-1 (G5665T) mutant variant had the
      lowest allelic frequency, and is significantly associated with sickle cell
      disease in Africa (P < 0.05). Similarly, haplotype frequencies were the same
      between cases and controls, except for the haplotype combining all mutant
      variants (T, C, 4a; P = 0.01). eNOS polymorphic variants are less frequent, with
      no significance with sickle cell disease in Africa. On the other hand, endothelin
      1 is associated with sickle cell disease, and has the capacity to redefine
      pathophysiology and possibly serve as modulator of disease phenotype. 

PMID- 24932103
TI  - Is drug use related to the choice of potentially more harmful methods in suicide
      attempts?
AB  - OBJECTIVE: To identify whether drug abuse is a risk factor for potentially more
      harmful methods of suicide attempts that could predict suicide completion in the
      future. METHODS: The study involved the assessment of 86 patients who attempted
      suicide and who were admitted to the emergency ward of a Southwestern Brazilian
      general hospital. RESULTS: Most patients were women (84.9%), young adults (30.53
      +/- 10.4 years), and single (61.6%). Recent drug use was reported by 53.5%, and
      25.6% reported the use of drugs during the 24-hour period immediately before the
      suicide attempt. Most patients (75.6%) ingested pills when attempting suicide-a
      method considered potentially less harmful. Hanging, jumping, gas inhaling, and
      wrist cutting accounted for 22.2% of the attempts. Considering dual diagnoses,
      54.7% presented with a depressive disorder, 8.1% with a disorder on the impulse
      control spectrum, and 26.7% reported an associated clinical condition. Recent
      drug use was predictive of the severity of the suicide attempt, as it was
      reported by 81% of those who engaged in more harmful attempts and by 46.2% of
      those who used less harmful methods (P < 0.01; odds ratio = 4.96; confidence
      interval: 1.5-16.4). CONCLUSION: The identified variables associated with the use
      of potentially more harmful methods in suicide attempts were gender (male),
      presence of an impulsive control disorder, and recent use of psychoactive drugs.

PMID- 24932104
TI  - Nutritional Effect of Oral Supplement Enriched in omega-3 Fatty Acids, Arginine,
      RNA on Immune Response and Leukocyte-platelet Aggregate Formation in Patients
      Undergoing Cardiac Surgery.
AB  - The aim of the present study was to investigate the influence of a supplement
      enriched in omega-3 fatty acids on immune responses and platelet-leukocyte
      complex formation in patients undergoing cardiac surgery. Patients in the
      supplement group (n = 7) took a supplement enriched in omega-3 fatty acids
      (Impact((r))) in addition to a hospital diet for five successive days before
      surgery; those in the control group (n = 7) took only hospital diet and did not
      take Impact((r)). Blood samples in both groups were collected at same time
      points. Before surgery, samples were collected five days before surgery, at the
      start of supplementation (baseline), and the end of supplementation
      (postoperative day (POD)-0). After surgery, samples were collected on POD-1 and
      POD-7. The expression of human leukocyte antigen (HLA)-DR, the ratio of CD4-/CD8
      positive cells, the production of interferon (IFN)-gamma by CD4-positive cells,
      plasma levels of cytokines, and leukocyte-platelet aggregates were measured.
      Before surgery (POD-0), the supplement caused significant increases in HLA-DR
      expression, CD4/CD8 ratio, and plasma levels of IFN-gamma; these levels were
      significantly higher compared to those in the control group (P < 0.05,
      respectively). After surgery (POD-1), all values dramatically decreased in
      comparison with those of POD-0; however, the values in the supplement group were
      significantly higher compared to their respective markers in the control group (P
      < 0.05, respectively). Significant differences of HLA-DR expression and CD4/CD8
      ratio persisted through POD-7. Before surgery (POD-0), plasma levels of
      interleukin (IL)-10 in the supplement group decreased significantly compared with
      those in the control group (P < 0.05). After surgery (POD-1), plasma levels of IL
      10 in both the control and supplement groups increased; these levels in the
      supplement group were significantly lower than those in the control group (P <
      0.05). Significant decreases in the percentage of leukocyte-platelet aggregates
      were found after supplementation; the difference between the supplement and the
      control groups was found on POD-0 and POD-1 (P < 0.05, respectively). In
      conclusion, the dietary supplement increased HLA-DR expression, the CD4/CD8
      ratio, and the production of IFN-gamma by CD4-positive cells; conversely, the
      levels of IL-10 and the formation of leukocyte-platelet aggregates before and
      after surgery were suppressed. These beneficial effects may decrease the
      incidence of complications after surgery. 

PMID- 24932105
TI  - Impact of aging on urinary excretion of iron and zinc.
AB  - PROJECT: Data about the influence of aging on urinary excretion of iron and zinc
      are scarce. The objective of the present study was to compare the concentration
      of zinc and iron in the urine of healthy elderly subjects and younger adults.
      PROCEDURE: Seven healthy elderly subjects and seven younger adults were selected
      and submitted to biochemical, clinical, and nutritional tests. After a fasting
      period, 12-hour urine was collected for the determination of iron and zinc
      concentrations by graphite furnace atomic absorption spectrophotometry. RESULTS:
      Urinary zinc and iron concentrations of the elderly subjects were not
      significantly different from that of younger adults. However, the total zinc and
      iron urinary clearance in 24 hours for the elderly was significantly higher
      compared with that of younger adults. CONCLUSION: There is an increase in urinary
      iron and zinc clearance with aging. The values reported in this manuscript may be
      used as references in future studies.

PMID- 24932106
TI  - Dorzolamide chlorhydrate versus acetazolamide in the management of chronic
      macular edema in patients with retinitis pigmentosa: description of three case
      reports.
AB  - AIMS: To assess the efficacy of topical dorzolamide for treating cystoid macular
      edema in patients with retinitis pigmentosa and minimize the secondary effects of
      maintenance therapy in patients with retinitis pigmentosa (RP) who present with
      chronic microcystic macular edema. METHODS: To replace acetazolamide systemic
      treatment, with a topical treatment using 2% dorzolamide in three patients. The
      methods performed were OCT scan with a Spectralis HRA-OCT, for the measurement of
      macular thickness and morphology; best corrected visual acuity was assessed using
      Early Treatment Diabetic Retinopathy Study (ETDRS), was assessed slit-lamp
      biomicroscopy, ocular tonometry, fundus biomiocrosopy, and color fundus
      photography. This therapeutic protocol has been applied and described in three
      patients. RESULTS: In all three tested patients, following the administration of
      dorzolamide in eye drop, we observed a remarkable decrease in macular edema,
      almost comparable to that obtained with acetazolamide per os. CONCLUSION: The
      study confirms the anti-edematogenic effect of topical dorzolamide in RP with
      recurring macular cysts, as this can have a favorable response with topical
      dorzolamide. In all the three examined patients, the instillation of topical
      dorzolamide caused a remarkable reduction in their macular edema, as highlighted
      on OCT.

PMID- 24932107
TI  - Vismodegib: the proof of concept in Basal cell carcinoma.
AB  - Although basal cell carcinoma (BCC) is the most common cancer worldwide, its
      metastatic dissemination is exceptional. Before 2012, we had a few treatment
      options available for metastatic or locally advanced cases. Management of these
      patients was complicated due to the lack of scientific data, the deterioration of
      a patient's general status, the patient's advanced age, and the presence of
      multiple comorbidities. The hedgehog signaling pathway is dysregulated in BCC.
      The exploration of this signaling pathway yielded to a major milestone in the
      treatment of advanced BCC. Vismodegib (GDC-0449), an oral small-molecule agent
      that targets the Hedgehog signaling pathway, demonstrates high levels of activity
      in clinical trials. It was approved in January 2012 for the treatment of locally
      advanced or metastatic BCC. Vismodegib confirms, once again, the interest in
      exploring the signal transduction pathways in cancers. 

PMID- 24932108
TI  - Efficacy and tolerability of pharmacotherapy options for the treatment of
      irritability in autistic children.
AB  - Children with autism have a high rate of irritability and aggressive symptoms.
      Irritability or self-injurious behavior can result in significant harm to those
      affected, as well as to marked distress for their families. This paper provides a
      literature review regarding the efficacy and tolerability of pharmacotherapy for
      the treatment of irritability in autistic children. Although antipsychotics have
      not yet been approved for the treatment of autistic children by many countries,
      they are often used to reduce symptoms of behavioral problems, including
      irritability, aggression, hyperactivity, and panic. However, among
      antipsychotics, the Food and Drug Administration has approved only risperidone
      and aripiprazole to treat irritability in autism. Among atypical antipsychotics,
      olanzapine and quetiapine are limited in their use for autism spectrum disorders
      in children because of high incidences of weight gain and sedation. In
      comparison, aripiprazole and ziprasidone cause less weight gain and sedation.
      However, potential QTc interval prolongation with ziprasidone has been reported.
      Contrary to ziprasidone, no changes were evident in the QT interval in any of the
      trials for aripiprazole. However, head-to-head comparison studies are needed to
      support that aripiprazole may be a promising drug that can be used to treat
      irritability in autistic children. On the other hand, risperidone has the
      greatest amount of evidence supporting it, including randomized controlled
      trials; thus, its efficacy and tolerability has been established in comparison
      with other agents. Further studies with risperidone as a control drug are needed.

PMID- 24932109
TI  - Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with
      acute ischemic stroke.
AB  - BACKGROUND: Cerebral ischemia promotes morphological reactions of the neurons,
      astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was
      to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation
      to stroke severity and degree of white matter lesions (WML). METHODS: A total of
      20 patients (mean age 76 years) were included within 5-10 days after acute
      ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National
      Institute of Health stroke scale). The age-related white matter changes (ARWMC)
      scale was used to evaluate the extent of WML on CT-scans. The concentrations of
      specific CSF biomarkers were analyzed. RESULTS: Patients with AIS had
      significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic
      protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with
      controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity,
      whereas NFL correlated with severity of WML (tested by Mann-Whitney test).
      CONCLUSIONS: Several CSF biomarkers increase in AIS, and they correlate to
      clinical stroke severity. However, only NFL was found to be a marker of degree of
      WML.

PMID- 24932110
TI  - Observations on dentine hypersensitivity in general dental practices in the
      United Arab Emirates.
AB  - Dentine hypersensitivity is a common clinical finding with a wide variation in
      prevalence values and etiological factors. The objective of this cross-sectional
      study was to investigate the prevalence and some etiological factors of dentine
      hypersensitivity of Emirati patients visiting general dental clinics in the
      United Arab Emirates (UAE) over a period of three calendar months. MATERIALS AND
      METHODS: Six general dental practitioners examined 204 Emirati patients over a
      period of three calendar months and patients who had dentine hypersensitivity
      diagnosed were questioned further about their smoking habits and the frequency,
      severity, and duration of their pain. Furthermore, cervical tooth surface loss
      was noted. RESULTS: A total of 55 patients were diagnosed as having dentine
      hypersensitivity, giving a prevalence figure of 27%. The most common teeth
      affected were the lower anterior teeth. CONCLUSIONS: The prevalence of dentine
      hypersensitivity in Emirati patients visiting a general dental clinic in the UAE
      was 27%. The most common etiology appeared to be the loss of cervical tooth
      surface structure.

PMID- 24932111
TI  - The evaluation of two rotary instrumentation techniques under "operator-related
      variables" standardized conditions.
AB  - OBJECTIVE: We aimed here to evaluate the enlargement characteristics of two
      nickel-titanium rotary instrument systems that use two different preparation
      techniques, in simulated root canals under "operator-related variables"
      standardized conditions. MATERIALS AND METHODS: A total of 40 simulated canals in
      resin blocks were divided into two groups as the Mtwo group for use with a single
      length technique and the ProTaper instrument system group for use with crown down
      technique. To standardize the operator-related variables, all preparations were
      carried out with a computer controlled device that was developed and used
      previously as described in a published study. The pre- and post-operative digital
      images of the canals were superimposed and measured at 11 levels from the apical
      tip. The distances between the pre- and post-operative outer lines of the root
      canals were measured at both the inner and outer sides of the curve. The amount
      of removed material and the symmetry of the preparations were evaluated.
      Statistical analyses were performed with Mann-Whitney test. RESULTS:
      Significantly more material was removed by Mtwo at 9 levels and by ProTaper at 2
      levels (P < 0.05) while no significant difference was determined at 11 levels.
      The preparations made with ProTaper were more symmetrical at 4 levels while no
      significant difference was determined at 7 levels. CONCLUSION: Mtwo removed
      significantly more material than ProTaper at different levels of the curved root
      canals. Mtwo and ProTaper made symmetrical preparations and maintained the
      original shape of the root canal at different levels under controlled operator
      related variables.

PMID- 24932112
TI  - The validation of a novel index assessing canine impactions.
AB  - AIM: The aims of this study are to determine the level of agreement of
      orthodontists in the management of impacted maxillary canines and test this
      agreement against a novel three-dimensional (3D) classification system (KPG
      index). MATERIALS AND METHODS: A total of 55 clinicians evaluated 18 impacted
      maxillary canines of variable complexity. For each case, they used a panoramic
      and maxillary standard occlusal radiographs derived from cone beam computed
      tomography. Clinicians were asked to rate each canine in one of four categories:
      Easy, moderate, difficult and extremely difficult. The obtained scores were
      tabulated and compared with a novel index rating the difficulty of canine
      impactions. Statistical package for the social science 17.0 was used to analyze
      the datasets and the kappa score was used to determine levels of agreement.
      RESULTS: The kappa score was 0.437. The levels of agreement in the novel index
      and the clinician scoring were as follows; easy (62.73%), moderate (60.59%),
      difficult (61.80%) and extremely difficult (72.72%). CONCLUSIONS: THE FOLLOWING
      CONCLUSIONS CAN BE DRAWN FROM THIS STUDY: (1) Clinicians are variable in rating
      the complexity of canine impactions using traditional radiographic techniques.
      (2) The novel index shows a good level of agreement with the clinician's
      perception of difficulty in orthodontic cases especially at the extremes of the
      spectrum. (3) This index based on the 3D coordinates of the spatial arrangement
      of the canine may be incorporated into clinical practice.

PMID- 24932113
TI  - The degree of color change, rebound effect and sensitivity of bleached teeth
      associated with at-home and power bleaching techniques: A randomized clinical
      trial.
AB  - AIM: The purpose of the present randomized clinical trial was to evaluate the
      color change, rebound effect and sensitivity of at-home bleaching with 15%
      carbamide peroxide and power bleaching using 38% hydrogen peroxide. MATERIALS AND
      METHODS: For bleaching techniques, 20 subjects were randomized in a split mouth
      design (at-home and power bleaching): In maxillary and mandibular anterior teeth
      (n = 20). Color was recorded before bleaching, immediately after bleaching, at 2
      weeks, 1, 3 and 6 month intervals. Tooth sensitivity was recorded using the
      visual analog scale. The Mann-Whitney test was used to compare both groups
      regarding bleaching effectiveness (DeltaE1), rebound effect (DeltaE2) and color
      difference between the rebounded tooth color and unbleached teeth (DeltaE3) while
      the Wilcoxon compared DeltaE within each group. Distribution of sensitivity was
      evaluated using the Chi-square test (alpha =0.05). RESULTS: There was no
      significant difference between groups regarding DeltaE1 and DeltaE3 (P > 0.05).
      Even though, DeltaE2 showed no significant difference between groups after
      bleaching as well as at 2 week, 1 month and 3 month follow-up periods (P > 0.05).
      Although, significant difference was found in DeltaE2 (P < 0.05 Mann-Whitney)
      between two methods after 6 months and a high degree of rebound effect was
      obtained with power bleaching. Within each group, there was no significant
      difference between DeltaE1 and DeltaE3 (P < 0.05 Wilcoxon). The distribution of
      sensitivity was identical with both techniques (P > 0.05). CONCLUSION: Bleaching
      techniques resulted in identical tooth whitening and post-operative sensitivity
      using both techniques, but faster color regression was found with power bleaching
      even though color regression to the baseline of the teeth in both groups was the
      same after 6 months.

PMID- 24932114
TI  - Insights into and relative effect of chitosan-H, chitosan-H-propolis, chitosan-H
      propolis-nystatin and chitosan-H-nystatin on dentine bond strength.
AB  - OBJECTIVE: The purpose of the study was to design and evaluate novel functional
      chitosan hydrogels (chitosan-H-propolis, chitosan-H-propolis-nystatin and
      chitosan-H-nystatin) by using the chitosan-H polymer as "dual function
      restorative materials". MATERIALS AND METHODS: The nystatin/antioxidant carrier
      gel was prepared by dispersion of the corresponding component in glycerol and 3%
      acetic acid with 5% chitosan gelling agent was then added to the dispersion with
      continuous mixing. The natural bio-adhesive functionalized chitosan hydrogels
      were combined with built in drug delivery system and bio-actives such as propolis
      in order to increase the dentin bond strength capacity and maintain therapeutic
      properties of the alternative drug delivery system. The surface morphology,
      release behaviors (physiological pH and also in acidic conditions), stability of
      nystatin:antioxidant:chitosan and the effect of the hydrogels on the shear bond
      strength of dentin were also evaluated. STATISTICAL ANALYSIS USED: Non-parametric
      ANOVA test was used to asses significance of higher shear bond values than
      dentine treated or not treated with phosphoric acid. RESULTS: The release of both
      nystatin and propolis confer the added benefit of dual action of a functional
      therapeutic delivery when comparing the newly designed chitosan-based hydrogel
      restorative materials to commercially available nystatin alone. Neither the
      release of nystatin nor the antioxidant stability was affected by storage.
      Chitosan-H, chitosan-propolis, chitosan-nystatin and chitosan-nystatin-propolis
      treated dentine gives significantly (P < 0.05) higher shear bond values (P <
      0.05) than dentine treated or not treated with phosphoric acid. CONCLUSION: The
      added benefits of their unique functionality involve increased dentin adhesive
      bond strengths (after 24 h and after 6 months) and positive influence on the
      nystatin release. Nystatin was a model therapeutic agent, evaluating the concept
      of using functional materials as carriers for pro-drugs as well as displaying a
      certain degree of defence mechanism for free radical damage of the novel
      functional drug delivery. Overall, there was an insignificant relapse in the
      shear bond strength after 6 months.

PMID- 24932115
TI  - A finite element analysis for a comparative evaluation of stress with two
      commonly used esthetic posts.
AB  - OBJECTIVES: The objective of this study was to evaluate stress distribution in
      the dentin and alveolar bone created by load application on simulated
      endodontically treated teeth with two different esthetic posts. MATERIALS AND
      METHODS: A finite element model was made and elastic moduli and poissons ratio of
      all the materials fed to the software. For both the models, a 100N force was
      applied on the lingual surface of the tooth at an angle of 45 degrees . Stress
      concentration and distribution were evaluated and noted down for both the posts.
      RESULTS: Finite element method revealed that Glass fibre post had homogenous
      distribution of stress whereas in zirconia post the stress was concentrated in
      the post. CONCLUSION: The present findings suggest that glass fibre post should
      be used in well-conserved radicular tooth structure and Zirconia post is
      indicated in weakened and grossly destructed tooth structure.

PMID- 24932116
TI  - Scanning electron microscopic evaluation of dentinal tubule penetration of
      Epiphany in severely curved root canals.
AB  - OBJECTIVE: The purpose of this study was to compare the depth of dentinal tubule
      sealer penetration in the apical thirds of severely curved root canals obturated
      with Resilon/Epiphany self-etch (SE) or gutta-percha/AH Plus using scanning
      electron microscopy. MATERIALS AND METHODS: A total of 34 extracted human
      mandibular molars with 25-40 degrees  curvature of the mesial root canal were
      selected for this study. After preparation, the mesiobuccal canals were randomly
      obturated with gutta-percha and AH Plus sealer or Resilon and Epiphany SE sealer.
      Sealer penetration was evaluated in 2 mm sections of the apical thirds of roots
      using scanning electron microscopy. Data were analyzed using the independent t
      test and Mann-Whitney U-test, with significance set at P < 0.05. RESULTS: Mean
      tubular penetration depth did not differ significantly between Resilon SE (172.22
      MUm) and AH Plus (122.18 MUm; P > 0.05). The density of sealer tags in the apical
      thirds of root canals was also equivalent (P > 0.05). CONCLUSION: Average
      penetration into dentinal tubules in the apical thirds of severely curved roots
      did not differ significantly between Epiphany SE and AH Plus.

PMID- 24932117
TI  - Effect of rotatory instrument speed on its capacity to remove demineralized and
      sound dentin.
AB  - OBJECTIVES: The aim of this study was to evaluate the capacity of two rotatory
      instruments (controlled speed electric motor [CSEM] - 300 rpm; conventional slow
      handpiece [CSHP] - 18,000 rpm) to remove sound and demineralized dentin, by
      examining prepared cavity walls using the scanning electron microscopy (SEM) and
      assessing loss of mass. MATERIALS AND METHODS: A total of 40 blocks of human
      occlusal dentin, measuring 5 mm * 5 mm * 4 mm (L * W * H), were divided into two
      groups according to the substrate type in which the cavity preparation was
      performed: D - demineralized dentin; and S - sound dentin (control group). The
      groups were subdivided according to the rotatory instrument used for cavity
      preparation (n = 10): CSEM (300 rpm); and CSHP (18,000 rpm). In half of the
      dentin blocks, caries lesion induction was performed for 6 weeks. The preparation
      of the cavities was performed on a standardizing machine, using a cylindrical
      tungsten carbide burr. Before and after the preparation, specimens were
      dehydrated in an incubator at 60 degrees C for 30 min. The initial and final mass
      (in mg) of each dentin block was measured 3 times using the digital precision
      balance to obtain the mean weight Following cavity preparation, all specimens
      were hemisected and SEM was used to blindly assess each half so that the lateral
      walls of the prepared cavity were measured in MUm, accepting the average of two
      measurements as the total depth of the preparation. Non-parametric Mann-Whitney
      analysis was performed with a 5% of significance level. RESULTS: Regarding the
      weight difference (mg), no significance was detected between the groups.
      Regarding depth (MUm), a significant difference was found between the groups, so
      that the CSRM showed lower cavity depth when compared with CSHP, both in sound
      and demineralized dentin. CONCLUSIONS: Controlled speed rotatory instruments were
      found to be more conservative in removing both sound and demineralized dentin, in
      terms of preparation and depth.

PMID- 24932118
TI  - Comparing the shear bond strength of direct and indirect composite inlays in
      relation to different surface conditioning and curing techniques.
AB  - OBJECTIVE: The aim of this study was to test the null hypothesis that different
      surface conditioning (etch and rinse and self-etch) and curing techniques (light
      cure/dual cure) had no effect on the shear bond strength of direct and indirect
      composite inlays. MATERIALS AND METHODS: A total of 112 extracted human molar
      teeth were horizontally sectioned and randomly divided into two groups according
      to restoration technique (direct and indirect restorations). Each group was
      further subdivided into seven subgroups (n = 8) according to bonding agent (etch
      and rinse adhesives Scotchbond multi-purpose plus, All-Bond 3, Adper Single Bond
      and Prime Bond NT; and self-etch adhesives Clearfil Liner Bond, Futurabond DC and
      G bond). Indirect composites were cemented to dentin surfaces using dual-curing
      luting cement. Shear bond strength of specimens was tested using a Universal
      Testing Machine. Two samples from each subgroup were evaluated under Scanning
      electron microscopy to see the failing modes. Data was analyzed using independent
      sample t-tests and Tukey's tests. RESULTS: Surface conditioning and curing of
      bonding agents were all found to have significant effects on shear bond strength
      (P < 0.05) of both direct and indirect composite inlays. With direct restoration,
      etch and rinse systems and dual-cured bonding agents yielded higher bond
      strengths than indirect restoration, self-etch systems and light-cured bonding
      agents. CONCLUSIONS: The results of the present study indicated that direct
      restoration to be a more reliable method than indirect restoration. Although etch
      and rinse bonding systems showed higher shear bond strength to dentin than self
      etch systems, both systems can be safely used for the adhesion of direct as well
      as indirect restorations.

PMID- 24932120
TI  - Prevalence of elongated styloid process in Saudi population of Aseer region.
AB  - OBJECTIVE: The study was performed to investigate the prevalence, morphology and
      calcification pattern of elongated styloid process in Saudi population of Aseer
      (Southern) region and its relation to gender and sub-age groups. MATERIALS AND
      METHODS: This study was analyzed digital panoramic radiographs of 1,162 adults.
      Any radiograph with questionable styloid process was excluded from the study. The
      apparent length of the styloid process was measured by a single experienced
      dental and maxillofacial Radiologist. The elongated styloid process was
      classified with the radiographic appearance based on the morphology and
      calcification pattern. The data were analyzed by using Student's t-test and Chi
      square test with P value less than 0.05. RESULTS: A total of 1,085 Digital
      panoramic radiographs showed elongated styloid process of which 686 (63.2%) were
      noticed in males and 399 (36.8%) were noticed in female patients. There was a
      statistical significant difference noticed in the mean difference of elongated
      styloid process between 20-29, 50-59 and 60 years and above sub-age groups. The
      elongated styloid process was more prevalent in elderly aged male patients (P <
      0.05). Type I morphology with calcified out line (a) was the most frequent
      pattern of calcification noticed in the present study. CONCLUSION: The panoramic
      radiographs are economical, easily accessible and useful diagnostic tool for
      early detection of elongated styloid process with or without symptoms. However,
      studies with larger sample size would further help to assess the prevalence of
      this elongated styloid process in Saudi population of various other regions.

PMID- 24932119
TI  - The effect of different root canal medicaments on the elimination of Enterococcus
      faecalis ex vivo.
AB  - OBJECTIVE: The aim of this study was to evaluate the antimicrobial effect of
      chlorhexidine gel (CHX-G) 2%, chlorhexidine powder (CHX-P) 1%, povidone-iodine
      (PVP-I), polyhexanide and camphorated-and-mentholated chlorophenol (ChKM) ex
      vivo. MATERIALS AND METHODS: For every medicament group 10 root segments (15 mm
      long) of extracted human teeth were prepared to ISO-size 45 and sterilized (n =
      50). The root segments were then inoculated with Enterococcus faecalis and
      aerobically incubated at 37 degrees C. After 1 week, ten root canals were filled
      with one of the medicaments, respectively and aerobically incubated at 37 degrees
      C for another week. Ten teeth served as positive controls and were filled with
      sterile saline solution. After 7 days, the medicaments were inactivated and all
      root canals were instrumented to ISO-size 50. The obtained dentin samples were
      dispersed in Ringer solution followed by the preparation of serial dilutions. 10
      MUl per sample were applied to an agar plate and incubated at 37 degrees C for 48
      h. The colony forming units were counted and the reduction factors (RFs) were
      calculated and statistically analyzed. RESULTS: Compared with the positive
      controls all medicaments exhibited an antibacterial effect against E. faecalis.
      The RFs for CHX-G, CHX-P and ChKM were significantly higher compared to PVP-I and
      polyhexanide (P < 0.05). In contrast to PVP-I and polyhexanide, CHX-G, CHX-P and
      ChKM were able to eliminate E. faecalis from all dentin samples. CONCLUSIONS:
      Within the limitations of this ex vivo investigation, 2% CHX-G and CHX-P were as
      effective as ChKM against E. faecalis. Thus, when choosing a root canal
      medicament the better biocompatibility of CHX compared with ChKM should be taken
      in consideration.

PMID- 24932121
TI  - In vitro evaluation of the fracture strength of all-ceramic core materials on
      zirconium posts.
AB  - OBJECTIVE: For most endodontically treated teeth, tooth-colored post-core systems
      are preferable for esthetic reasons. Therefore, improvements in material strength
      must also consider tooth colored post-core complexes. The objective of this study
      was to evaluate the difference in tooth colored post-core complex strengths.
      MATERIALS AND METHODS: A total of 33 human maxillary central incisor teeth were
      used for this study, with three groups of 11 teeth. Three different methods were
      used to fabricate all-ceramic post-core restorations: zirconia blanks, Cerec 3D
      milled to one-piece post-core restorations (Test Group 1); feldspathic cores
      (from feldspathic prefabricated CAD/CAM blocks) adhesively luted to CosmoPost
      zirconia posts (Test Group 2); and IPS Empress cores directly pressed to
      CosmoPost zirconia posts (Test Group 3). All-ceramic crowns from feldspathic
      ceramic were constructed using a CAD/CAM system (Cerec 3D) for all specimens. The
      post-core complexes were tested to failure with the load applied at 45 degrees 
      angled relative to the tooth long axis. The load at fracture was recorded.
      RESULTS: The maximum fracture strength of the milled zirconia cores (Test Group
      1) was 577 N; corresponding values for the milled feldspathic cores (Test Group
      2) and the pressed cores (Test Group 3) were 586 and 585 N, respectively.
      Differences were not statistically significant at P < 0.05 (P = 0.669).
      CONCLUSIONS: All-ceramic cores adhesively luted on zirconia posts and one-piece
      all-ceramic zirconium post-core structures offer a viable alternative to
      conventional pressing.

PMID- 24932122
TI  - A clinical efficacy of 30% ethenolic extract of Indian propolis and RecaldentTM
      in management of dentinal hypersensitivity: A comparative randomized clinical
      trial.
AB  - OBJECTIVE: The aim of this study is to evaluate the efficacy of 30% ethenolic
      extract of Indian propolis compared with Recaldent(TM) (casein phosphopeptide
      amorphous calcium phosphate) in reduction of dentinals hypersensitivity, a
      randomized, double-blind, split mouth, controlled clinical trial was conducted
      among the patients residing in Central Jail. MATERIALS AND METHODS: A sample of
      73 teeth from 13 patients having at least three teeth with dentinal
      hypersensitivity (DH) were randomly allocated into three treatment groups: Group
      A: 30% ethenolic extract of Indian propolis, Group B: Recaldent(TM), Group C:
      Sterile water. Verbal rating scale was used to record the degree of
      hypersensitivity based on patient's response to tactile and air blast stimuli.
      The baseline scores were obtained. Each intervention group received applications
      of their respective agents consecutively on 1(st), 7(th), 14(th), and 21(st) day.
      After each application the scores were recorded. RESULTS: Both the 30% Indian
      propolis and Recaldent(TM) showed significant reduction in DH. CONCLUSION:
      Recaldent(TM) was found to be significantly better in reducing the DH compared to
      propolis and sterile water (P < 0.01).

PMID- 24932123
TI  - Antimicrobial efficiency of photodynamic therapy with different irradiation
      durations.
AB  - OBJECTIVE: This study aimed to evaluate the antimicrobial efficiency of PDT and
      the effect of different irradiation durations on the antimicrobial efficiency of
      PDT. MATERIALS AND METHODS: Sixty freshly extracted human teeth with a single
      root were decoronated and distributed into five groups. The control group
      received no treatment. Group 1 was treated with a 5% sodium hypochlorite (NaOCl)
      solution. Groups 2, 3, and 4 were treated with methylene-blue photosensitizer and
      660-nm diode laser irradiation for 1, 2, and 4 min, respectively. The root canals
      were instrumented and irrigated with NaOCl, ethylenediamine-tetraacetic acid, and
      a saline solution, followed by autoclaving. All the roots were inoculated with an
      Enterococcus faecalis suspension and brain heart infusion broth and stored for 21
      days to allow biofilm formation. Microbiological data on microorganism load were
      collected before and after the disinfection procedures and analyzed with the
      Wilcoxon ranged test, the Kruskal-Wallis test, and the Dunn's test. RESULTS: The
      microorganism load in the control group increased. The lowest reduction in the
      microorganism load was observed in the 1-min irradiation group (Group 2 = 99.8%),
      which was very close to the results of the other experimental groups (99.9%).
      There were no significant differences among the groups. CONCLUSIONS: PDT is as
      effective as conventional 5% NaOCl irrigation with regard to antimicrobial
      efficiency against Enterococcus faecalis.

PMID- 24932124
TI  - Thickness of immediate dentin sealing materials and its effect on the fracture
      load of a reinforced all-ceramic crown.
AB  - OBJECTIVES: The objective of this study is to evaluate, in vitro, the thickness
      of immediate dentin sealing (IDS) materials on full crown preparations and its
      effect on the fracture load of a reinforced all-ceramic crown. MATERIALS AND
      METHODS: SIXTY PREMOLARS RECEIVED FULL CROWN PREPARATION AND WERE DIVIDED INTO
      THE FOLLOWING GROUPS ACCORDING TO THE IDS TECHNIQUE: G1-control; G2-Clearfil SE
      Bond; and G3-Clearfil SE Bond and Protect Liner F. After the impressions were
      taken, the preparations were temporized with acrylic resin crowns. IPS empress 2
      restorations were fabricated and later cemented on the preparations with Panavia
      F. 10 specimens from each group were submitted to fracture load testing. The
      other 10 specimens were sectioned buccolingually before the thicknesses of
      Panavia F, Clearfil SE Bond and Protect Liner F were measured in 10 different
      positions using a microscope. RESULTS: According to analysis of variance and
      Tukey's test, the fracture load of Group 3 (1300 N) was significantly higher than
      that of Group 1 (1001 N) (P < 0.01). Group 2 (1189 N) was not significantly
      different from Groups 1 and 3. The higher thickness of Clearfil SE Bond was
      obtained in the concave part of the preparation. Protect Liner F presented a more
      uniform range of values at different positions. The thickness of Panavia F was
      higher in the occlusal portion of the preparation. CONCLUSIONS: The film
      thickness formed by the IDS materials is influenced by the position under the
      crown, suggesting its potential to increase the fracture load of the IPS empress
      2 ceramic crowns.

PMID- 24932125
TI  - A three-dimensional finite element study on the stress distribution pattern of
      two prosthetic abutments for external hexagon implants.
AB  - OBJECTIVE: The purpose of this study was to evaluate the mechanical behavior of
      two different straight prosthetic abutments (one- and two-piece) for external hex
      butt-joint connection implants using three-dimensional finite element analysis
      (3D-FEA). MATERIALS AND METHODS: Two 3D-FEA models were designed, one for the two
      piece prosthetic abutment (2 mm in height, two-piece mini-conical abutment,
      Neodent) and another one for the one-piece abutment (2 mm in height, Slim Fit one
      piece mini-conical abutment, Neodent), with their corresponding screws and
      implants (Titamax Ti, 3.75 diameter by 13 mm in length, Neodent). The model
      simulated the single restoration of a lower premolar using data from a
      computerized tomography of a mandible. The preload (20 N) after torque
      application for installation of the abutment and an occlusal loading were
      simulated. The occlusal load was simulated using average physiological bite force
      and direction (114.6 N in the axial direction, 17.1 N in the lingual direction
      and 23.4 N toward the mesial at an angle of 75 degrees  to the occlusal plan).
      RESULTS: The regions with the highest von Mises stress results were at the bottom
      of the initial two threads of both prosthetic abutments that were tested. The one
      piece prosthetic abutment presented a more homogeneous behavior of stress
      distribution when compared with the two-piece abutment. CONCLUSIONS: Under the
      simulated chewing loads, the von Mises stresses for both tested prosthetic
      abutments were within the tensile strength values of the materials analyzed which
      thus supports the clinical use of both prosthetic abutments.

PMID- 24932126
TI  - Ceramic veneers with minimum preparation.
AB  - The aim of this article is to describe the possibility of improving dental
      esthetics with low-thickness glass ceramics without major tooth preparation for
      patients with small to moderate anterior dental wear and little discoloration.
      For this purpose, a carefully defined treatment planning and a good communication
      between the clinician and the dental technician helped to maximize enamel
      preservation, and offered a good treatment option. Moreover, besides restoring
      esthetics, the restorative treatment also improved the function of the anterior
      guidance. It can be concluded that the conservative use of minimum thickness
      ceramic laminate veneers may provide satisfactory esthetic outcomes while
      preserving the dental structure. 

PMID- 24932127
TI  - Congenital granular cell tumor in newborn.
AB  - The congenital granular cell tumor (CGCT) is quite scarce at the infant. The
      patient, who has a 2-day-old female newborn, was admitted to the Department of
      Pediatric Dentistry. Baby had a smooth surfaced, non-fixated mass, found on the
      anterior part of the mandibular alveole, developing from the gingival mucosa.
      Clinical examination showed a 1 cm * 1 cm * 1.8 cm pedunculated, regular, pink
      colorful soft-tissue gob on the alveolar crest to the left side of the mandible.
      The gob was removed on the seventh postnatal day under general anesthesia. Then,
      the specimen was evaluated histopathologically. Post-operative recovery and
      surgical site healing was satisfactory. The CGCT is a rare, degenerative or
      reactive lesion of the oral cavity. The mass may surgically remove if the
      diagnosis is not definite clinically and this can lead therapeutic effect. 

PMID- 24932128
TI  - An unusual case of brown tumor of hyperparathyroidism associated with ectopic
      parathyroid adenoma.
AB  - Brown tumor is a giant cell lesion associated with hyperparathyroidism. It is a
      non-neoplastic condition and represents terminal stage of the remodeling process
      in hyperparathyroid state. We report a case of brown tumor with multiple lesions
      in craniofacial region associated with ectopic parathyroid adenoma revealed after
      acute L-thyroxine poisoning. This case report emphasizes on the need for routine
      biochemical investigations along with serum calcium, phosphorus and parathyroid
      hormone levels in patients on thyroxine therapy. 

PMID- 24932129
TI  - A minimally invasive technique for the management of severely fluorosed teeth: A
      two-year follow-up.
AB  - OBJECTIVE: Severely fluorosed and heavily discolored teeth that have large enamel
      defects give rise to esthetic concerns and require permanent treatment. In such
      cases, restorative techniques such as porcelain or composite laminate veneers or
      crowns are generally preferred, in which tooth preparation is inevitably
      required. MATERIALS AND METHODS: This clinical report describes a patient with
      severely fluorosed teeth who was successfully treated with a minimally invasive
      technique including enamel microabrasion (6.6% hydrochloric acid slurry with
      silicon carbide micro-particles, Opalustre, Ultradent Products, Inc., South
      Jordan, UT, USA) followed by in-office bleaching (38% hydrogen peroxide,
      Opalescence Boost, Ultradent). Enamel microabrasion was conducted in two visits
      while three visits were required for in-office bleaching. Patient was followed-up
      after 2 years. RESULT: A slight staining had occurred during this period, but it
      was acceptable for patient. No adverse effects were observed. CONCLUSIONS: The
      minimally invasive technique including enamel microabrasion and in-office
      bleaching was efficient and may represent a good alternative to traditional
      restorative techniques for the management of severely fluorosed teeth.

PMID- 24932130
TI  - The total occlusal convergence of the abutment of a partial fixed dental
      prosthesis: A definition and a clinical technique for its assessment.
AB  - The abutment(s) of a partial fixed dental prosthesis (PFDP) should have a minimal
      total occlusal convergence (TOC), also called a taper, in order to ensure
      adequate retention of a PFDP that will be made for the abutment(s), given the
      height of the abutment(s). This article reviews the concept of PFDP abutment TOC
      and presents an alternative definition of what TOC is, defining it as the extent
      to which the shape of an abutment differs from an ideal cylinder shape of an
      abutment. This article also reviews experimental results concerning what is the
      ideal TOC in degrees and explores clinical techniques of estimating the TOC of a
      crown abutment. The author suggests that Dentists use high magnification loupes
      (*6-8 magnification or greater) or a surgical operating microscope when preparing
      crown abutments, to facilitate creating a minimum abutment TOC. 

PMID- 24932131
TI  - Avenues into Food Planning: A Review of Scholarly Food System Research.
AB  - This review summarizes several avenues of planning inquiry into food systems
      research, revealing gaps in the literature, allied fields of study and mismatches
      between scholarly disciplines and the food system life cycle. Planners and
      scholars in associated fields have identified and defined problems in the food
      system as 'wicked' problems, complex environmental issues that require systemic
      solutions at the community scale. While food justice scholars have contextualized
      problem areas, planning scholars have made a broad case for planning involvement
      in solving these wicked problems while ensuring that the functional and
      beneficial parts of the food system continue to thrive. This review maps the
      entry points of scholarly interest in food systems and planning's contributions
      to its study, charting a research agenda for the future.

PMID- 24932132
TI  - Extra Corporeal Membrane Oxygenation (ECMO) in three HIV-positive patients with
      acute respiratory distress syndrome.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving bridging
      procedure in patients with severe acute respiratory distress syndrome (ARDS).
      Official indications for ECMO are unclear for immunocompromised and HIV-positive
      patients affected by severe hypoxemia. Uncertainties are related to prognosis and
      efficacy of treatment of the underlying disease. However, the care of patients
      with HIV infection has advanced since the introduction of highly active
      antiretroviral therapy (HAART), with increased life expectancy and decreased
      mortality. CASE PRESENTATION: Three HIV-infected patients with AIDS were admitted
      to ICU and were treated with ECMO: a 21 years old Caucasian female with
      congenital HIV infection presented with Pneumocystis jirovecii pneumonia (PJP); a
      38 years old Caucasian female with HIV-HCV infection and L. pneumophila
      pneumonia; a 24 years old Caucasian male with fever, cough weight loss and PJP
      pneumonia. Two patients were alive, with a good immunovirological profile and
      they went back to their previous quality of life. The last patient died with
      septic shock after three months of ICU stay. CONCLUSION: ECMO was effective in
      three HIV-positive patients with an otherwise fatal respiratory failure. All
      patients had severe immunosuppression and/or limited antiretroviral options. A
      multidisciplinary critical team is needed to individualize the use of ECMO in
      immunocompromised patients, including those with HIV infection.

PMID- 24932133
TI  - A pilot study to evaluate incorporating eye care for children into reproductive
      and child health services in Dar-es-Salaam, Tanzania: a historical comparison
      study.
AB  - BACKGROUND: Many blinding eye conditions of childhood are preventable or
      treatable, particularly in developing countries. However, primary eye care (PEC)
      for children is poorly developed, leading to unnecessary visual loss. Activities
      for control by health workers entail interventions for systemic conditions
      (measles, vitamin A deficiency), identification and referral of children with
      sight threatening conditions and health education for caregivers. This pilot
      study evaluated integrating a package of activities to promote child eye health
      into Reproductive and Child Health (RCH) services in Dar-es-Salaam, Tanzania.
      METHODS:  DESIGN: historical comparison study. Fifteen Clinical Officers and 15
      nurses in 15 randomly selected RCH clinics were trained in PEC for children in
      July 2010. They were given educational materials (poster and manual) and their
      supervisors were orientated. Knowledge and practices were assessed before and 3
      weeks after training. One year later their knowledge and practices were compared
      with a different group of 15 Clinical Officers and 15 nurses who had not been
      trained. RESULTS: Before training staff had insufficient knowledge to identify,
      treat and refer children with eye diseases, even conjunctivitis. Some recommended
      harmful practices or did not know that cataract requires urgent referral. Eye
      examination, vitamin A supplementation of mothers after delivery and cleaning the
      eyes at birth with instillation of antibiotics (Crede's prophylaxis) were not
      routine, and there were no eye-specific educational materials. Three weeks after
      training several clinics delivering babies started Crede's prophylaxis, vitamin A
      supplementation of women after delivery increased from 83.7% to 100%, and all
      staff included eye conditions in health education sessions. At one year, trained
      staff were more likely to correctly describe, diagnose and treat conjunctivitis
      (z=2.34, p=0.04)(30%-vs-60.7%). Mystery mothers observed health education
      sessions in 7/10 RCH clinics with trained staff, five (71.4%) of which included
      eye conditions. CONCLUSIONS: Primary eye care for children in Dar-es-Salaam is
      inadequate but training RCH staff can improve knowledge in the short term and
      change practices. Attendance by mothers and their children is high in RCH
      clinics, making them ideal for delivery of PEC. Ongoing supportive supervision is
      required to maintain knowledge and practices, as well as systems to track
      referrals.

PMID- 24932134
TI  - Anti-cancer activity of glucosamine through inhibition of N-linked glycosylation.
AB  - BACKGROUND: We have reported that the glucosamine suppressed the proliferation of
      the human prostate carcinoma cell line DU145 through inhibition of STAT3
      signaling. DU145 cells autonomously express IL-6 and the IL-6/STAT3 signaling is
      activated. IL-6 receptor subunits are subject to N-glycosylation, a
      posttranslational modification which is important for protein stability and
      function. We speculated that the inhibition of STAT3 phosphorylation by
      glucosamine might be a functional consequence of the reduced N-glycosylation of
      gp130. METHODS: The human prostate cancer cell lines DU145 and PC-3 and human
      melanoma cell line A2058 were used in this study. Glucosamine effects on N
      glycosylation of glycoproteins were determined by Western blot analysis. IL-6
      binding to DU145 cells was analyzed by flow cytometry. The cell proliferation
      suppression was investigated by colorimetric Janus green staining method.
      RESULTS: In DU145 cells glucosamine reduced the N-glycosylation of gp130,
      decreased IL-6 binding to cells and impaired the phosphorylation of JAK2, SHP2
      and STAT3. Glucosamine acts in a very similar manner to tunicamycin, an inhibitor
      of protein N-glycosylation. Glucosamine-mediated inhibition of N-glycosylation
      was neither protein- nor cell-specific. Sensitivity of DU145, A2058 and PC-3
      cells to glucosamine-induced inhibition of N-glycosylation were well correlated
      to glucosamine cytotoxicity in these cells. CONCLUSION: Our results suggested
      that the glucosamine-induced global inhibition of protein N-glycosylation might
      be the basic mechanism underlying its multiple biochemical and cellular effects.

PMID- 24932135
TI  - An estrogen analogue and promising anticancer agent refrains from inducing
      morphological damage and reactive oxygen species generation in erythrocytes,
      fibrin and platelets: a pilot study.
AB  - BACKGROUND: 2-Methoxyestradiol is known to have antitumour and antiproliferative
      action in vitro and in vivo. However, when 2-methoxyestradiol is orally
      administered, it is rapidly oxidized by the enzyme 17I2-hydroxysteriod
      dehydrogenase in the gastrointestinal tract. Therefore, 2-methoxyestradiol never
      reaches high enough concentrations in the tissue to be able to exert these
      antitumour properties. This resulted in the in silico-design of 2
      methoxyestradiol analogues in collaboration with the Bioinformatics and
      Computational Biology Unit (UP) and subsequent synthesis by iThemba
      Pharmaceuticals (Pty) Ltd (Modderfontein, Midrand, South Africa). One such a
      novelty-designed analogue is 2-ethyl-3-O-sulphamoyl-estra-1, 3, 5(10)16-tetraene
      (ESE-16). METHODS: This pilot study aimed to determine the morphological effect
      and possible generation of reactive oxygen species by ESE-16 on erythrocytes and
      platelet samples (with and without added thrombin) by means of scanning electron
      microscopy, transmission electron microscopy and flow cytometry. RESULTS:
      Erythrocytes and platelets were exposed to ESE-16 at a concentration of 180nM for
      24A hours. Scanning- and transmission electron microscopy indicated that ESE-16
      did not cause changes to erythrocytes, platelets or fibrin networks. Flow
      cytometry measurements of hydrogen peroxide and superoxide indicated that ESE-16
      does not cause an increase in the generation of reactive oxygen species in these
      blood samples. CONCLUSION: Further in vivo research is warranted to determine
      whether this novel in silico-designed analogue may impact on development of
      future chemotherapeutic agents and whether it could be considered as an
      antitumour agent.

PMID- 24932136
TI  - Sampling of Organic Solutes in Aqueous and Heterogeneous Environments Using
      Oscillating Excess Chemical Potentials in Grand Canonical-like Monte Carlo
      Molecular Dynamics Simulations.
AB  - Solute sampling of explicit bulk-phase aqueous environments in grand canonical
      (GC) ensemble simulations suffer from poor convergence due to low insertion
      probabilities of the solutes. To address this, we developed an iterative
      procedure involving Grand Canonical-like Monte Carlo (GCMC) and molecular
      dynamics (MD) simulations. Each iteration involves GCMC of both the solutes and
      water followed by MD, with the excess chemical potential (MUex) of both the
      solute and the water oscillated to attain their target concentrations in the
      simulation system. By periodically varying the MUex of the water and solutes over
      the GCMC-MD iterations, solute exchange probabilities and the spatial
      distributions of the solutes improved. The utility of the oscillating-MUex GCMC
      MD method is indicated by its ability to approximate the hydration free energy
      (HFE) of the individual solutes in aqueous solution as well as in dilute aqueous
      mixtures of multiple solutes. For seven organic solutes: benzene, propane,
      acetaldehyde, methanol, formamide, acetate, and methylammonium, the average MUex
      of the solutes and the water converged close to their respective HFEs in both 1 M
      standard state and dilute aqueous mixture systems. The oscillating-MUex GCMC
      methodology is also able to drive solute sampling in proteins in aqueous
      environments as shown using the occluded binding pocket of the T4 lysozyme L99A
      mutant as a model system. The approach was shown to satisfactorily reproduce the
      free energy of binding of benzene as well as sample the functional group
      requirements of the occluded pocket consistent with the crystal structures of
      known ligands bound to the L99A mutant as well as their relative binding
      affinities.

PMID- 24932137
TI  - Role of Backbone Dipole Interactions in the Formation of Secondary and
      Supersecondary Structures of Proteins.
AB  - We present a generic solvated coarse-grained protein model that can be used to
      characterize the driving forces behind protein folding. Each amino acid is coarse
      grained with two beads, a backbone, and a side chain. Although the backbone beads
      are modeled as polar entities, side chains are hydrophobic, polar, or charged,
      thus allowing the exploration of how sequence patterning determines a protein
      fold. The change in orientation of the atoms of the coarse-grained unit is
      captured by the addition of two oppositely charged dummy particles inside the
      backbone coarse-grained bead. These two dummy charges represent a dipole that can
      fluctuate, thus introducing structural polarization into the coarse-grained
      model. Realistic alpha/beta content is achieved de novo without any biases in the
      force field toward a particular secondary structure. The dipoles created by the
      dummy particles interact with each other and drive the protein models to fold
      into unique structures depending on the amino acid patterning and presence of
      capping residues. We have also characterized the role of dipole-dipole and dipole
      charge interactions in shaping the secondary and supersecondary structure of
      proteins. Formation of helix bundles and beta-strands are also discussed.

PMID- 24932138
TI  - The Transmembrane Helix Tilt May Be Determined by the Balance between Precession
      Entropy and Lipid Perturbation.
AB  - Hydrophobic helical peptides interact with lipid bilayers in various modes,
      determined by the match between the length of the helix's hydrophobic core and
      the thickness of the hydrocarbon region of the bilayer. For example, long helices
      may tilt with respect to the membrane normal to bury their hydrophobic cores in
      the membrane, and the lipid bilayer may stretch to match the helix length. Recent
      molecular dynamics simulations and potential of mean force calculations have
      shown that some TM helices whose lengths are equal to, or even shorter than, the
      bilayer thickness may also tilt. The tilt is driven by a gain in the helix
      precession entropy, which compensates for the free energy penalty resulting from
      membrane deformation. Using this free energy balance, we derived theoretically an
      equation of state, describing the dependence of the tilt on the helix length and
      membrane thickness. To this end, we conducted coarse-grained Monte Carlo
      simulations of the interaction of helices of various lengths with lipid bilayers
      of various thicknesses, reproducing and expanding the previous molecular dynamics
      simulations. Insight from the simulations facilitated the derivation of the
      theoretical model. The tilt angles calculated using the theoretical model agree
      well with our simulations and with previous calculations and measurements.

PMID- 24932139
TI  - Impact of windows and daylight exposure on overall health and sleep quality of
      office workers: a case-control pilot study.
AB  - STUDY OBJECTIVE: This research examined the impact of daylight exposure on the
      health of office workers from the perspective of subjective well-being and sleep
      quality as well as actigraphy measures of light exposure, activity, and sleep
      wake patterns. METHODS: Participants (N = 49) included 27 workers working in
      windowless environments and 22 comparable workers in workplaces with
      significantly more daylight. Windowless environment is defined as one without any
      windows or one where workstations were far away from windows and without any
      exposure to daylight. Well-being of the office workers was measured by Short Form
      36 (SF-36), while sleep quality was measured by Pittsburgh Sleep Quality Index
      (PSQI). In addition, a subset of participants (N = 21; 10 workers in windowless
      environments and 11 workers in workplaces with windows) had actigraphy recordings
      to measure light exposure, activity, and sleep-wake patterns. RESULTS: Workers in
      windowless environments reported poorer scores than their counterparts on two SF
      36 dimensions--role limitation due to physical problems and vitality--as well as
      poorer overall sleep quality from the global PSQI score and the sleep
      disturbances component of the PSQI. Compared to the group without windows,
      workers with windows at the workplace had more light exposure during the
      workweek, a trend toward more physical activity, and longer sleep duration as
      measured by actigraphy. CONCLUSIONS: We suggest that architectural design of
      office environments should place more emphasis on sufficient daylight exposure of
      the workers in order to promote office workers' health and well-being.

PMID- 24932140
TI  - Associations between sleep duration, sleep quality, and cognitive test
      performance among older adults from six middle income countries: results from the
      Study on Global Ageing and Adult Health (SAGE).
AB  - BACKGROUND: Alterations in sleep architecture are common among older adults.
      Previous studies have documented associations between sleep duration, sleep
      quality, and cognitive performance in older individuals, yet few studies have
      examined these trends using population-based samples from non-Western societies.
      The present cross-sectional study uses nationally representative datasets from
      six countries to test several hypotheses related to sleep patterns and cognitive
      function. METHODS: Data were drawn from the first wave of the World Health
      Organization's study on global ageing and adult health (SAGE), a longitudinal
      study using samples of older adults (>= 50 years old) in 6 middle-income
      countries (China, Ghana, India, Russian Federation, South Africa, and Mexico).
      Self-report data provided information on sleep quality and sleep duration over
      the previous 2 nights, and 5 cognitive tests (immediate and delayed verbal
      recall, forward and backward digit span, and verbal fluency) were used to create
      a composite z-score of cognitive performance. RESULTS: Individuals with
      intermediate sleep durations (> 6-9 h/night) exhibited significantly higher
      cognitive scores than individuals with short sleep (0-6 h/night; p < 0.001) or
      long sleep duration (> 9 h/night; p < 0.001). Self-reported sleep quality was
      positively correlated with cognitive z-score (p < 0.05). Significant sex
      differences were observed; men generally had higher sleep quality and cognitive
      scores, while women reported longer sleep durations. DISCUSSION: This study
      documented positive correlations between cognitive scores and sleep quality, and
      between cognitive z-scores and intermediate sleep duration. These findings are
      clinically important given the growing rates of dementia and aging populations
      globally.

PMID- 24932141
TI  - A prospective questionnaire study in 100 healthy sleepers: non-bothersome forms
      of recognizable sleep disorders are still present.
AB  - STUDY OBJECTIVES: Despite several polysomnographic normative studies and multiple
      surveys of sleep disorders in the general population, few data have been
      collected on healthy sleepers. We aimed to survey the characteristics of healthy
      sleep. METHODS: We prospectively investigated the sleep history of 100 subjects
      of a representative population sample who reported undisturbed sleep and in whom
      relevant sleep disorders were ruled out by a two-step screening procedure.
      Approximately four subjects had to be contacted for identifying 1 eligible
      subject who participated. RESULTS: The median reported time in bed was from 23:00
      (21:30-02:00) to 07:00 (05:30-11:00). The total sleep duration was 7.3 h (5-10
      h), varying from 7.5 h in the age group <= 30 years to 7 h in subjects aged 40-60
      years and to 8 h in subjects > 60 years (p = 0.002). The median sleep efficiency
      was high (93.3%, range: 55.6% to 100%). Fifty-one subjects reported occasional
      snoring. Forty-five subjects reported sporadic non-bothersome sleep-related
      movement disorders (25 sleep-related leg cramps, 22 lifetime bruxism, 5 restless
      legs syndrome), and 36 had a history of sporadic non-bothersome parasomnias (27
      nightmares, 12 sleepwalking, 1 sleep paralysis). CONCLUSION: In this population
      of healthy sleepers, snoring is the most common finding. Moreover, non-bothersome
      forms of recognizable sleep-related movement disorders and parasomnias are
      surprisingly common. These findings may suggest that diagnostic criteria of sleep
      disorders should not only be based on the presence of symptoms but also account
      for a minimum frequency or discomfort.

PMID- 24932142
TI  - The effect of continuous positive air pressure (CPAP) on nightmares in patients
      with posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA).
AB  - OBJECTIVES: Post-Traumatic Stress Disorder (PTSD) is increasingly prevalent among
      Veterans characterized by recurrent nightmare and disrupted sleep. Veterans with
      PTSD also have a high prevalence of obstructive sleep apnea (OSA) and untreated
      OSA worsens the sleep-related symptoms of PTSD. In our study, we hypothesized
      that among PTSD-afflicted Veterans with OSA, CPAP therapy may reduce the
      frequency of nightmares and a better CPAP compliance may be associated with
      increased symptom improvement. METHODS: We retrospectively reviewed medical
      records to identify OSA patients treated in a VA medical center who also carried
      a diagnosis of PTSD (n = 69). Data about patient characteristics and
      polysomnographic findings were extracted. Repeated-measures t-tests were
      performed, comparing mean nightmare frequency and Epworth sleepiness score (ESS)
      before and after CPAP treatment. Multiple linear regressions were done to
      identify factors predicting CPAP compliance. A logistic regression analysis was
      also done to estimate the odds of subjective improvement in PTSD symptoms with
      CPAP. RESULTS: CPAP therapy reduced the mean ESS from 14.62 to 8.52 (p < 0.001)
      and the mean number of nightmares per week from 10.32 to 5.26 (p < 0.01). Reduced
      nightmare frequency after CPAP treatment was best predicted by CPAP compliance (p
      < 0.001). Every 10% increase in CPAP compliance almost doubled the odds of
      benefitting by CPAP (odds ratio = 1.92, 95% CI = 1.47-2.5). CONCLUSIONS: In
      Veterans with PTSD and OSA, CPAP therapy reduces PTSD-associated nightmares and
      improves overall PTSD symptoms. We recommend that all PTSD patients should be
      screened clinically for symptoms of OSA and receive CPAP treatment whenever
      possible to improve PTSD symptoms.

PMID- 24932143
TI  - Adaptive servoventilation for treatment of opioid-associated central sleep apnea.
AB  - RATIONALE: Opioids have become part of contemporary treatment in the management
      of chronic pain. Although severe daytime ventilatory depression is uncommon,
      chronic use of opioids could be associated with severe central and obstructive
      sleep apnea. OBJECTIVES: To determine the acute efficacy, and prolonged use of
      adaptive servoventilation (ASV) to treat central sleep apnea in patients on
      chronic opioids. METHODS: Twenty patients on opioid therapy referred for
      evaluation of obstructive sleep apnea (OSA) were found to have central sleep
      apnea (CSA). The first 16 patients underwent continuous positive airway pressure
      (CPAP) titration, which showed persistent CSA. With the notion that CSA will be
      eliminated with continued use of CPAP, 4 weeks later, 9 of the 16 patients
      underwent a second CPAP titration which proved equally ineffective. Therefore,
      therapy with CPAP was abandoned. All patients underwent ASV titration. MAIN
      RESULTS: Diagnostic polysomnography showed an average apnea-hypopnea index (AHI)
      of 61/h and a central-apnea index (CAI) of 32/h. On CPAP 1, AHI was 34/h and CAI
      was 20/h. Respective indices on CPAP 2 were AHI 33/h and CAI 19/h. During
      titration with ASV, CAI was 0/h and the average HI was 11/h on final pressures.
      With a reduction in AHI, oxyhemoglobin saturation nadir increased from 83% to
      90%, and arousal index decreased from 29/h of sleep to 12/h on final ASV
      pressures. Seventeen patients were followed for a minimum of 9 months and up to 6
      years. The mean long-term adherence was 5.1 +/- 2.5 hours. CONCLUSIONS: Chronic
      use of opioids could be associated with severe CSA which remains resistant to
      CPAP therapy. ASV device is effective in the treatment of CSA and over the long
      run, most patients remain compliant with the device. Randomized long-term studies
      are necessary to determine if treatment of sleep apnea with ASV improves quality
      of life and the known mortality associated with opioids.

PMID- 24932144
TI  - The epidemic of opioid use: implications for the sleep physician.

PMID- 24932145
TI  - Individual variability and predictors of driving simulator impairment in patients
      with obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with driving
      impairment and road crashes. However, daytime function varies widely between
      patients presenting a clinical challenge when assessing crash risk. This study
      aimed to determine the proportion of patients showing "normal" versus "abnormal"
      driving simulator performance and examine whether anthropometric, clinical, and
      neurobehavioral measures predict abnormal driving. METHODS: Thirty-eight OSA
      patients performed a 90-min simulated driving task under 3 conditions: normal
      sleep, restricted sleep (4 h in bed), and normal sleep + alcohol (BAC~0.05 g/dL).
      Patients were classified as "resilient" drivers if, under all 3 experimental
      conditions their mean steering deviation fell within 2 standard deviations of the
      mean steering deviation of 20 controls driving under baseline normal sleep
      conditions, or a "vulnerable" driver if mean steering deviation was outside this
      range in at least one experimental condition. Potentially predictive baseline
      anthropometric, clinical, neurocognitive, and cortical activation measures were
      examined. RESULTS: Of the 38 OSA patients examined, 23 (61%) and 15 (39%) were
      classified as resilient and vulnerable drivers, respectively. There were no
      differences in baseline measures between the groups, although the proportion of
      females was greater and self-reported weekly driving exposure was less among
      vulnerable drivers (p < 0.05). On univariate analysis gender, weekly driving
      hours, and auditory event related potential P2 amplitude were weakly associated
      with group status. Multivariate analysis showed weekly driving hours (OR 0.69,
      95%CI, 0.51-0.94, p = 0.02) and P2 amplitude (OR 1.34, 95%CI 1.02-1.76, p =
      0.035) independently predicted vulnerable drivers. CONCLUSIONS: Most OSA patients
      demonstrated normal simulated driving performance despite exposure to further
      sleep loss or alcohol. Most baseline measures did not differentiate between
      resilient and vulnerable drivers, although prior driving experience and cortical
      function were predictive. Novel measures to assist identification of OSA patients
      at risk of driving impairment and possibly accidents are needed. TRIAL
      REGISTRATION: Data presented in this manuscript was collected as part of a
      clinical trial "Experimental Investigations of Driving Impairment in Obstructive
      Sleep Apnea." Trial ID: ACTRN12610000009011, URL:
      http://www.anzctr.org.au/trial_view.aspx?ID=334979.

PMID- 24932146
TI  - Obstructive sleep apnea, obesity, and the development of acute respiratory
      distress syndrome.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) may increase the risk of respiratory
      complications and acute respiratory distress syndrome (ARDS) among surgical
      patients. OSA is more prevalent among obese individuals; obesity can predispose
      to ARDS. HYPOTHESIS: It is unclear whether OSA independently contributes towards
      the risk of ARDS among hospitalized patients. METHODS: This is a pre-planned
      retrospective subgroup analysis of the prospectively identified cohort of 5,584
      patients across 22 hospitals with at least one risk factor for ARDS at the time
      of hospitalization from a trial by the US Critical Illness and Injury Trials
      Group designed to validate the Lung Injury Prediction Score. A total of 252
      patients (4.5%) had a diagnosis of OSA at the time of hospitalization; of those,
      66% were obese. Following multivariate adjustment in the logistic regression
      model, there was no significant relationship between OSA and development of ARDS
      (OR = 0.65, 95%CI = 0.32-1.22). However, body mass index (BMI) was associated
      with subsequent ARDS development (OR = 1.02, 95%CI = 1.00-1.04, p = 0.03).
      Neither OSA nor BMI affected mechanical ventilation requirement or mortality.
      CONCLUSIONS: Prior diagnosis of OSA did not independently affect development of
      ARDS among patients with at least one predisposing condition, nor the need for
      mechanical ventilation or hospital mortality. Obesity appeared to independently
      increase the risk of ARDS.

PMID- 24932147
TI  - Pilot study of nasal expiratory positive airway pressure devices for the
      treatment of childhood obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVES: Alternative therapies for childhood obstructive sleep apnea
      syndrome (OSAS) are needed as OSAS may persist despite adenotonsillectomy, and
      continuous positive airway pressure (CPAP) adherence is low. Nasal expiratory
      positive airway pressure (NEPAP) devices have not been studied in children. We
      hypothesized that NEPAP would result in polysomnographic improvement. Further, we
      aimed to determine NEPAP adherence, effects on sleepiness, behavior, and quality
      of life. METHODS: A randomized, double-blind, placebo-controlled, crossover pilot
      study was performed. CPAP candidates, 8-16 years old, underwent NEPAP and placebo
      polysomnograms. Subjects with >= 50% reduction in the apnea hypopnea index (AHI)
      from placebo to NEPAP night or AHI < 5/h on NEPAP night wore NEPAP at home for 30
      days. Adherence was assessed by daily phone calls/emails and collecting used
      devices. RESULTS: Fourteen subjects (age 13.4 +/- 1.9 years, BMI z-scores 2.2 +/-
      1 [mean +/- SD]) were studied. There was significant improvement in the
      obstructive apnea index with NEPAP vs. placebo: 0.6 (0-21.1)/h vs. 4.2 (0-41.9)/h
      (median [range], p = 0.010) and trends for improvement in other polysomnographic
      parameters. However, responses were variable, with 3 subjects not improving and 2
      worsening. Older children and those with less hypercapnia had a better response.
      Eight subjects were sent home with devices; one was lost to follow-up, and
      adherence in the remainder was 83% of nights; these subjects had a significant
      improvement in sleepiness and quality of life. CONCLUSIONS: NEPAP devices are a
      potential alternative therapy for OSAS in a small subset of children. Due to
      variability in individual responses, efficacy of NEPAP should be evaluated with
      polysomnography. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier:
      NCT01768065.

PMID- 24932148
TI  - Association between symptoms of sleep-disordered breathing and speech in children
      with craniofacial malformations.
AB  - STUDY OBJECTIVE: Sleep-disordered breathing (SDB) and speech difficulties are
      common problems in children with craniofacial malformations (CFM). The present
      study was designed to investigate whether resonance issues identified during
      speech assessment are associated with parental report of SDB symptoms in children
      with CFM. METHODS: Children aged 2-18 years with congenital CFM attending at the
      Craniofacial Anomalies Program from March 2007 to April 2011 were screened for
      SDB symptoms using the Sleep-Related Breathing Disturbance Scale of the Pediatric
      Sleep Questionnaire. Speech evaluation, based on the Pittsburgh Weighted Speech
      Scale score, was the tool used to investigate velopharyngeal dysfunction (VPD)
      based on speech perceptual assessment. RESULTS: A total of 488 children with
      congenital CFM were included. Overall 81% were Caucasian and 24% were
      overweight/obese. Twenty-four percent of children screened positive for SDB and
      35% had VPD. Children with VPD were no more likely to screen positive for SDB
      than children without VPD (26% vs. 23%, p = 0.38). However, children with
      previous sphincter pharyngoplasty (SP) were more likely to have hyponasality (51%
      vs. 12%, p = 0.0001) and reduced or absent nasal emission (33% vs. 16%, p =
      0.008). In a logistic regression, the adjusted odds ratio for SDB for those with
      hyponasality was 2.10 (95%CI 1.21-3.61, p = 0.008) and for those with reduced or
      absent nasal emission was 1.75 (95%CI 1.06-2.88, p = 0.028). CONCLUSION: Symptoms
      of sleep disordered breathing are common in children with craniofacial
      malformations especially if they have undergone sphincter pharyngoplasty; many of
      these children can be identified by measures of resonance on routine speech
      evaluation.

PMID- 24932149
TI  - Oxidative stress in children with obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with
      cardiovascular consequences, including accelerated atherosclerosis and
      endothelial dysfunction. Increased lipid peroxidation, a marker of oxidative
      stress, has been identified in adults with OSA in a severity-dependent manner,
      with attenuation following treatment with continuous positive airway pressure
      therapy. Studies on oxidative stress in children with OSA are sparse and results
      are inconclusive. The objective of this study was to compare lipid peroxidation
      in children with OSA to non-OSA children. METHODS: A prospective cross-sectional
      study of 26 children with polysomnography-confirmed OSA (oAHI >= 5/h TST) was
      conducted. Thirty age- and body mass index z-score-matched children with primary
      snoring (PS) served as a comparison group (oAHI <= 1/h TST). Fasting blood
      samples were obtained on the morning following the sleep study. Plasma oxidized
      low-density lipoprotein (oxLDL) concentrations were measured by enzyme-linked
      immunosorbent assay. RESULTS: There were no group differences in patient
      characteristics and their lipid profiles. The mean oxLDL levels of the OSA group
      were significantly higher than those of the comparison group (53.1 +/- 13.0 vs.
      45.7 +/- 10.0 U/L, respectively, p = 0.02). There was a significant positive
      correlation between plasma oxLDL and the apnea hypopnea index (r = 0.29, p =
      0.03) and between oxLDL and the oxygen desaturation index (r = 0.51, p = 0.003),
      and a significant negative correlation between SpO2 nadir and oxLDL (r = -0.29, p
      = 0.03). CONCLUSIONS: OSA in children is associated with increased lipid
      peroxidation in a severity-dependent manner. Lipid peroxidation levels correlate
      with the degree of intermittent hypoxia.

PMID- 24932150
TI  - Validation of two depression screening instruments in a sleep disorders clinic.
AB  - STUDY OBJECTIVES: Depression is a commonly diagnosed comorbidity in sleep
      disorder clinics. However, screening instruments for major depressive episode
      (MDE) have not been validated in this setting. We aimed to validate the Hospital
      Anxiety and Depression Scale (HADS) and the Beck Depression Inventory - Fast
      Screen (BDI-FS) with the Mini International Neuropsychiatric Interview (MINI) in
      patients with suspected obstructive sleep apnea (OSA). DESIGN: Cross-sectional
      study. SETTING: Academic center. PARTICIPANTS: One hundred one new patients with
      a clinical suspicion of OSA, as assessed by a sleep physician. MEASUREMENTS: MDE,
      generalized anxiety disorder (GAD), and panic disorder (PD) were assessed by (1)
      a diagnostic interview utilizing the MINI and (2) by two self-report
      questionnaires: HADS and BDI-FS. A receiver operating characteristic (ROC)
      analysis was undertaken to assess which HADS and BDI-FS threshold yielded the
      highest correlation for a diagnosis of MDE and/or GAD/PD as assessed with an
      interview conducted using the MINI. RESULTS: A HADS-Depression score >= 8 gave
      optimal sensitivity (83.1%) and specificity (83.3%) with an area under the ROC
      curve (AUC) 0.851 for predicting the diagnosis of MDE. A HADS-Anxiety score >= 11
      gave an optimal sensitivity (93.1%) and specificity (84.7%) with an AUC 0.911 for
      predicting the diagnosis of GAD/PD. A BDI-FS threshold >= 6 gave optimal
      sensitivity (86.7%) and specificity (82.9%) with an AUC 0.897 for MDE.
      CONCLUSION: The HADS and BDI-FS are accurate screening instruments with high
      concurrent validity for identifying the probability of a patient having MDE and
      in the case of HADS-GAD and PD disorder in a sleep disorders clinic.

PMID- 24932151
TI  - Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy
      refractory insomnia in a hospitalized patient.
AB  - The case of a 59-year-old woman psychiatrically hospitalized with comorbid
      insomnia, suicidal ideation, and generalized anxiety disorder is presented.
      Pharmacologic therapies were unsuccessful for treating insomnia prior to and
      during hospitalization. Intensive sleep deprivation was initiated for 40
      consecutive hours followed by a recovery sleep period of 8 hours. Traditional
      components of cognitive behavioral therapy for insomnia (CBTi), sleep
      restriction, and stimulus control therapies, were initiated on the ward. After
      two consecutive nights with improved sleep, anxiety, and absence of suicidal
      ideation, the patient was discharged. She was followed in the sleep clinic for
      two months engaging in CBTi. Treatment resulted in substantial improvement in her
      insomnia, daytime sleepiness, and anxiety about sleep. Sleep deprivation regimens
      followed by a restricted sleep recovery period have shown antidepressant effects
      in depressed patients. Similar treatment protocols have not been investigated in
      patients with pharmacotherapy refractory insomnia and generalized anxiety
      disorder.

PMID- 24932152
TI  - CPAP treats muscle cramps in patients with obstructive sleep apnea.
AB  - We describe a case series of 4 patients with varying degrees of obstructive sleep
      apnea who incidentally had a history of nocturnal leg cramps. None of the
      patients had periodic limb movements during the study and denied symptoms
      consistent with restless legs syndrome. In 3 of the 4 patients, nocturnal leg
      cramps resolved with CPAP treatment for OSA, while the fourth patient noted near
      resolution of cramping after starting CPAP. In patients presenting with muscle
      cramps, obstructive sleep apnea should be considered.

PMID- 24932153
TI  - Multidisciplinary sleep centers: strategies to improve care of sleep disorders
      patients.
AB  - Current emphasis on patient outcomes within sleep medicine, with a particular
      focus on quality improvement and contained costs, calls for sleep specialists to
      develop innovative models for long-term care and management of sleep disorders
      patients. Multidisciplinary sleep centers can facilitate highest-quality care
      that is timely and cost-effective. Effective resource use in a multidisciplinary
      sleep center can help minimize fragmentation of care, reduce effort duplication,
      and control costs. Proposed strategies to help achieve a balance between quality
      of care and cost-effectiveness include: (1) multidisciplinary specialty clinics,
      (2) optimized use of information technology, and (3) adoption of reliable
      performance measures.

PMID- 24932154
TI  - A case of insomnia in an elderly woman.

PMID- 24932155
TI  - The lumpers and splitters paradox.

PMID- 24932156
TI  - A RERA by any other name... .

PMID- 24932157
TI  - The "paradox" issue.

PMID- 24932158
TI  - Association between OSA and severe fatigue in patients with multiple sclerosis
      (MS).

PMID- 24932159
TI  - Obstructive sleep apnea is an under-recognized and consequential morbidity in
      multiple sclerosis.

PMID- 24932161
TI  - Women, Aging, and HIV: Clinical Issues and Management Strategies.
AB  - Women are living longer with HIV infection. How best to manage the multiple co
      morbidities and polypharmacy that are a hallmark of HIV infected individuals has
      not been studied. We explore incorporating principles of gerontology,
      particularly multimorbidity and polypharmacy, to optimize the health of HIV
      infected women. Multimorbidity and polypharmacy are important issues for HIV
      infected women. Incorporating a gerontologic approach may optimize outcomes until
      research provides more definitive answers as to how best to collaborate with HIV
      infected women to provide them with optimal care. A case study is used to guide
      the discussion.

PMID- 24932162
TI  - What Promotes Wisdom in 12-Step Recovery?
AB  - Research investigations on twelve-step groups such as Alcoholics Anonymous (AA)
      and Narcotics Anonymous (NA) have addressed a number of resources associated with
      12-step recovery. However, little is known about the role of wisdom, and whether
      aspects of 12-step participation might increase this resource among 12-step
      members. An exploratory analysis revealed that participants who reported having a
      "spiritual awakening" and considered themselves "members" of 12-step groups
      reported significantly higher levels of wisdom. Twelve-step meeting attendance
      was not significantly related to wisdom scores. Findings suggest certain aspects
      of 12-step involvement are associated with wisdom and may play a role in
      substance abuse recovery.

PMID- 24932163
TI  - Successful management of a colo-duodenal fistula in a patient with Crohn's
      disease using a double lumen gastro-jejunostomy tube.
AB  - A 41-year-old woman was admitted with upper abdominal pain, vomiting and fever.
      Abdominal CT scan showed a colo-duodenal fistula with inflammatory thickening of
      the transverse colon. The patient's general health was poor because of
      hypoalbuminemia and coagulopathy. Endoscopy showed a fistula at the lower
      duodenal angle and the stomach was filled with refluxed stool. Ileostomy and
      percutaneous endoscopic gastrostomy were performed at that time and a double
      lumen gastro-jejunostomy inserted through the gastrostomy to allow both gastric
      drainage and distal enteral feeding. Nutrition support was gradually converted
      from parenteral to enteral feeding. Colonoscopy showed stenosis of the transverse
      colon with a colo-colonic fistula near the stenosis. Two months later, right hemi
      colectomy and closure of the colo-duodenal fistula were performed. The resected
      specimen showed stenosis and a fistula in the transverse colon due to Crohn's
      disease. The colo-colonic fistula was present and the colo-duodenal fistula had
      almost closed due to fibrosis. The postoperative course was uneventful and the
      patient was discharged after administration of infliximab. Use of a double lumen
      gastro-jejunostomy tube was effective in improving the patient's general
      condition. This therapeutic strategy allowed the safe conduct of major resection
      in a high-risk patient. 

PMID- 24932164
TI  - Cystic liver infection after living donor liver transplantation: a case report.
AB  - There are no reports of cystic liver infection after liver transplantation.
      Herein, we report a rare case of cystic liver graft infection after living donor
      liver transplantation (LDLT). The patient was a 24-year-old man with primary
      sclerosing cholangitis who underwent right lobe graft LDLT. Preoperative
      abdominal computed tomography (CT) revealed a liver cyst at segment 8 of the
      donor liver. Biliary reconstruction was performed with hepaticojejunostomy. The
      postoperative course was uneventful until the patient developed a high fever and
      abdominal pain 15 months after LDLT. Abdominal contrast CT revealed abscess
      formation. Percutaneous drainage of the cyst was performed and purulent liquid
      was drained. The fever gradually subsided after treatment. On follow-up CT, the
      size of the infected liver cyst was decreased. Clinicians should be aware of the
      potential for cystic liver infection when using grafts with liver cysts,
      particularly when biliary reconstruction is performed with hepaticojejunostomy. 

PMID- 24932165
TI  - Spontaneous colon perforations associated with a vascular type of ehlers-danlos
      syndrome.
AB  - Ehlers-Danlos syndrome, vascular type (vEDS) (MIM #130050) is an autosomal
      dominant disorder caused by mutation in the type III collagen gene, COL3A1,
      leading to fragility of blood vessels, bowel and uterus that leads to spontaneous
      rupture. We report a previously undiagnosed vEDS patient with bowel
      complications. A 20-year-old female patient was referred to our hospital with
      abdominal pain. Computed tomography showed notable dilatation of the sigmoid
      colon with intraperitoneal fluid. Laparotomy revealed dilatation of the sigmoid
      colon, breakdown of serosa and muscularis propria of the sigmoid colon with
      impending perforation, and intra-abdominal hemorrhage caused by breakdown of the
      mesenterium. Resection of the sigmoid colon with Hartmann's pouch and an end
      colostomy were performed. Physical examination showed joint hypermobility,
      translucent skin with venous prominence and facial structure abnormalities.
      Genetic analysis using cDNA extracted from the patient's fibroblasts by reverse
      transcriptase polymerase chain reaction direct sequencing showed a missense
      mutation within the triple helix region of COL3A1 (c.2150 G>A; Gly717Asp). 

PMID- 24932166
TI  - Pulmonary Mycobacterium avium Infection in a Patient with Crohn's Disease under
      Azathioprine Treatment.
AB  - Anti-tumor necrosis factor alpha therapy is known as a risk factor of non
      tuberculous mycobacteria (NTM) infection. However, there are few reports of NTM
      infection under treatment with thiopurine agents. We herein report a first case
      of pulmonary infection caused by Mycobacterium avium complex (MAC) in a patient
      with Crohn's disease under treatment with thiopurine. After starting antibiotics
      therapy for NTM including clarithromycin, rifampicin, ethambutol and
      streptomycin, MAC infection was well controlled, and she kept clinical remission
      even without azathioprine. In conclusion, our case emphasizes the importance of
      considering NTM infection in respiratory complications of inflammatory bowel
      disease patients under immunosuppressive therapies. 

PMID- 24932167
TI  - Perianal Paget's Disease Co-Associated with Anorectal Adenocarcinoma: Primary or
      Secondary Disease?
AB  - Perianal Paget's disease (PPD) represents a skin neoplasm which can be either
      primary or secondary to carcinoma from an adjacent internal organ. PPD with
      underlying colorectal adenocarcinoma is usually looked upon as a secondary
      disease. We report a rare case of co-associated PPD and anorectal adenocarcinoma.
      The PPD was found to be located near the anorectal adenocarcinoma with normal
      tissues between them. Immunohistochemical stains demonstrated that the Paget's
      cells were CK7+/GCDFP-15-/CK20-/MUC2-/CDX2-, whereas the anorectal adenocarcinoma
      was shown to be CK7+/GCDFP-15-/CK20+/MUC2+/CDX2+. This immunological phenotypic
      profile supported the notion that PPD and anorectal adenocarcinoma were of
      different origins, but could not define the exact origins of PPD. In our
      determination, this case was a primary PPD with anorectal adenocarcinoma. PPD
      remains a heterogeneous and complex pathology, and additional studies are
      required to differentiate between the various possible origins. 

PMID- 24932168
TI  - S100A6 and c-Kit-Positive Spindle Cell Melanoma of the Dorsal Foot.
AB  - Spindle cell melanoma, which is a rare form of melanoma, is clinically and
      histopathologically difficult to diagnose from a variety of nonmelanocytic
      spindle cell tumors. We describe a 42-year-old Japanese woman with amelanotic
      melanoma that comprised spindle cells with positive c-kit and S100A6 staining.
      The use of c-kit and S100A6 might be useful for improving the diagnosis. 

PMID- 24932169
TI  - Cutaneous Adverse Reactions to Highly Antiretroviral Therapy in HIV-Positive
      Patients.
AB  - Adverse drug reactions to highly antiretroviral therapy (HAART) are major
      obstacles in its success. Although overall mortality from HIV has dramatically
      declined owing to HAART, these antiretroviral regimens have been associated with
      a wide spectrum of severe cutaneous reactions. The severity of cutaneous adverse
      reactions varies greatly, and some may be difficult to manage. To optimize
      adherence and efficacy of antiretroviral treatment, clinicians must focus on
      preventing adverse effects whenever possible, and distinguish those that are self
      limited from those that are potentially serious. This paper presents the case of
      a serious cutaneous adverse reaction to Atripla in a HIV-positive 50-year-old
      Caucasian woman. 

PMID- 24932170
TI  - Idiopathic Seidlmayer's Purpura: A Case Report.
AB  - Acute hemorrhagic edema of infancy (AHEI) was considered a rare form of Henoch
      Schonlein purpura; however, it is now regarded as an independent disease
      typically involving patients aged 4-24 months. The authors describe the clinical
      case of a toddler aged 8 months, with skin erythematous pomphoid lesions, treated
      at home with topical steroids without benefits. The appearance of new lesions and
      the worsening of the previous skin signs induced the parents to drive the child
      to the hospital. The medical history revealed the administration of a vaccine
      dose 2 months before. 

PMID- 24932171
TI  - Retroperitoneal sarcoma involving unilateral double ureter: management, treatment
      and psychological implications.
AB  - The case of a 45-year-old woman who was admitted to our university hospital for
      polymenorrhea, weight gain and pain in the left iliac region is reported. An
      abdominal ultrasound revealed a 9.5 * 5.2-cm, hypoechoic and inhomogeneous mass
      located on the left side of the pelvis and behind the ovary. The patient
      underwent surgery. The pelvic mass was firmly anchored to the small intestine,
      colon, sigma and uterine fundus. After removing the adhesions, double ureters,
      which had been incorporated in the mass, were observed on the left side.
      Resection of the unilateral double ureters was necessary in order to remove the
      entire mass, and thereafter, a left salpingoophorectomy was performed. A
      histological examination showed a malignant retroperitoneal mass. Termino
      terminal ureteral anastomosis with two double-J stents was carried out. Total
      hysterectomy with preservation of the right adenexum and regional lymphadenectomy
      was performed. The purpose of this case report is to discuss the physical and
      psychological implications related to the combination of two rare entities:
      leiomyosarcoma and a double ureter located within the mass. A literature review
      on the clinical management and psychological aspects from a female cancer
      patient's perspective undergoing surgery with the aforementioned disorders will
      be discussed. 

PMID- 24932172
TI  - Primary clear-cell sarcoma in the mediastinum.
AB  - We report a case of primary clear-cell sarcoma (CCS) in the mediastinum. In
      October 2011, a 63-year-old man was admitted to our hospital for surgical
      resection. The tumor was completely excised by video-assisted thoracoscopic
      surgery. The tumor was well encapsulated and did not invade the pleura.
      Histological examination led to a final diagnosis of primary CCS in the
      mediastinum. The patient remains alive without evidence of recurrence at 15
      months after surgery. 

PMID- 24932173
TI  - Epithelioid myoepithelioma of the accessory parotid gland: pathological and
      magnetic resonance imaging findings.
AB  - Tumors of the accessory parotid gland (APG) are rare, and pleomorphic adenoma
      (PA) is the most common benign APG tumor subtype. Myoepithelioma of the APG is
      much rarer than PA, and to date, only 5 cases have been sporadically reported in
      the English literature. We describe the clinicopathological and MRI findings of
      an epithelioid myoepithelioma of the APG that was treated in our hospital. The
      patient's only clinical symptom was a slow-growing and painless mid-cheek mass.
      The tumor was suspected to be PA before surgery based on the following MRI
      findings: (1) a well-circumscribed and lobulated contour, (2) isointensity and
      hyperintensity relative to the muscle on T1- and T2-weighted images (WIs),
      respectively, (3) good enhancement on contrast-enhanced T1-WIs, (4) peripheral
      hypointensity on T2-WIs, and (5) a gradual time-signal intensity curve
      enhancement pattern on gadolinium-enhanced dynamic MRI. The tumor was completely
      resected via a standard parotidectomy approach, and the postoperative
      pathological examination of the tumor, including immunohistochemistry, confirmed
      the diagnosis of epithelioid myoepithelioma. As it is hardly possible to
      distinguish myoepithelioma from PA and low-grade malignant tumors preoperatively,
      a pathological examination using frozen sections is helpful for surgical strategy
      related decisions. 

PMID- 24932175
TI  - Two cases of mastectomy after Paclitaxel + bevacizumab therapy for locally
      advanced breast cancer.
AB  - INTRODUCTION: Locally advanced breast cancer (LABC) deteriorates the quality of
      life (QOL) of the affected patients. Combination chemotherapy or extended
      chemotherapy is considered to help to shrink local lesions. CASE 1: A 71-year-old
      female with a history of tympanitis and cystitis with methicillin-resistant
      Staphylococcus aureus (MRSA) visited our hospital. There was a tumor of 7 cm in
      diameter in her right breast with skin ulceration. Paclitaxel + bevacizumab
      therapy was started, and after five cycles of therapy, a mastectomy with axillary
      dissection was performed. Chemotherapy with anthracycline was avoided for fear of
      activating the MRSA. After the operation, the patient's wound opened. However, it
      naturally epithelialized. CASE 2: A 41-year-old female visited our hospital due
      to a tumor of 8 cm in diameter in her right breast with skin ulceration. Four
      cycles of paclitaxel + bevacizumab therapy were started, and her tumor almost
      disappeared during the first cycle. Then, doxorubicin + cyclophosphamide therapy
      was performed for four cycles, and a mastectomy with axillary dissection was
      performed. Her postoperative course was good. DISCUSSION: Chemotherapy with
      bevacizumab or extended chemotherapy is generally not considered to contribute to
      a survival improvement. However, such therapy contributes in increasing the
      response to chemotherapy, and should be considered for patients with LABC to
      shrink the local lesions and improve the QOL.

PMID- 24932174
TI  - Combination Chemotherapy of Azacitidine and Cetuximab for Therapy-Related Acute
      Myeloid Leukemia following Oxaliplatin for Metastatic Colorectal Cancer.
AB  - Therapy-related leukemia (TRL) has been reported to occur after treatment with
      alkylating agents and/or topoisomerase II inhibitors. Oxaliplatin (OXP) is used
      as a key drug for the treatment of colorectal cancer (CRC). Cisplatin and
      carboplatin have been linked with TRL, but the involvement of OXP is
      questionable. A 74-year-old male was diagnosed with peritoneal metastasis from
      CRC in July 2011. The patient received nine cycles of 5-fluorouracil (5-FU),
      leucovorin (LV), and OXP (mFOLFOX-6 regimen) and three cycles of 5-FU and LV
      only, resulting in a clinical complete response. However, recurrence of CRC was
      detected by CT within 3 months after the last course of chemotherapy. In April
      2013, laboratory tests showed pancytopenia and 15% blast cells. A bone marrow
      examination revealed multilineage dysplasia and 20.4% myeloblasts. Cytogenetic
      analysis indicated a complex karyotype that included chromosome 5 and 7
      abnormalities. The patient was diagnosed with TRL and treated with a combination
      of azacitidine (AZA) and cetuximab (Cmab) for both cancers. AZA might be useful
      in TRL when a patient needs to be treated simultaneously for more than one
      primary cancer because of its low toxicity. Moreover, Cmab is an effective
      therapeutic tool in TRL patients with metastatic CRC with the wild-type K-ras
      gene. 

PMID- 24932177
TI  - B-cell malignant lymphoma presenting as otitis media and mastoiditis associated
      with sinus thrombosis.
AB  - Cerebral venous thrombosis as a manifestation of paraneoplastic angitis and
      otitis media, revealing non-Hodgkin B-cell lymphoma (NHBL), is extremely rare. A
      57-year-old woman presented with headache, auditory disturbance and recalcitrant
      otitis media. Magnetic resonance imaging showed brain edema in the temporal lobe
      and transverse sinus thrombosis. External drainage under antibiotic treatment was
      repeated based on a diagnosis of invasive otitis media and mastoiditis associated
      with infectious sinus thrombosis, but the condition deteriorated progressively.
      Open surgery for otitis media was performed 6 years after the initial symptoms
      and after a tumorous lesion had been detected in the middle ear. Pathological
      findings revealed NHBL. We report a rare case of NHBL presenting as otitis media
      and mastoiditis associated with sinus thrombosis, and a literature review. 

PMID- 24932176
TI  - Dandy-walker malformation and down syndrome association: good developmental
      outcome and successful endoscopic treatment of hydrocephalus.
AB  - The association of Down syndrome (DS) with Dandy Walker malformation (DWM) is
      extremely rare, with only 3 cases reported to date. All cases reported have shown
      a bad life expectancy and a bad developmental outcome. The present case reveals
      the possibility of a good prognosis. A 19-month-old male patient had successful
      endoscopic hydrocephalus treatment and a good developmental outcome. He probably
      had a better outcome because of good DS and DWM prognostic parameters. Our
      patient suffered from a DWM with vermis identification of 2 fissures and 3 lobes
      and a DS with a well-preserved tonus, which was not associated with other
      congenital systemic defects. We may conclude that the prognosis of DS-DWM
      association may separately depend on the degree of clinical and neurological
      involvement of each malformation. 

PMID- 24932178
TI  - Steroid-Responsive Epilepsia Partialis Continua with Anti-Thyroid Antibodies: A
      Spectrum of Hashimoto's Encephalopathy?
AB  - BACKGROUND: When a neuropsychiatric symptom due to encephalopathy develops in a
      patient with anti-thyroid antibodies, especially when the symptom is steroid
      responsive, Hashimoto's encephalopathy (HE) needs to be included in the
      differential diagnosis of the patient. Although HE is an elusive disease, it is
      thought to cause various clinical presentations including seizures, myoclonus,
      and epilepsia partialis continua (EPC). CASE REPORT: We present the case of a 33
      year-old Japanese woman who acutely developed EPC in the right hand as an
      isolated manifestation. A thyroid ultrasound showed an enlarged hypoechogenic
      gland, and a thyroid status assessment showed euthyroid with high titers of
      thyroid antibodies. A brain MRI revealed a nodular lesion in the left precentral
      gyrus. Corticosteroid treatment resulted in a cessation of the symptom.
      CONCLUSIONS: A precentral nodular lesion can be responsible for steroid
      responsive EPC in a patient with anti-thyroid antibodies and may be caused by HE.
      The serial MRI findings of our case suggest the presence of primary
      demyelination, with ischemia possibly due to vasculitis around the demyelinating
      lesion.

PMID- 24932179
TI  - Acute retinal necrosis in childhood.
AB  - BACKGROUND: Acute retinal necrosis (ARN) is a viral syndrome consisting of
      uveitis/vitritis, occlusive vasculitis and peripheral necrosis. Few incidents are
      reported in children. The etiology is reactivated herpes simplex virus (HSV) or
      varicella-zoster virus (VZV). Treatment with acyclovir is often used. The
      administration of oral glucocorticosteroids is of unproven benefit. Prognosis is
      variable but poor. METHODS: Three weeks after contracting mild chickenpox, a
      healthy 4-year-old girl developed blurred vision in her right eye. Severely
      reduced visual acuity was noted, together with anterior uveitis, 'mutton-fat'
      precipitates and vitral flare. Retinal vasculitis with necrosis was present.
      Serology for toxoplasma, cytomegalovirus and HIV was negative, while HSV and VZV
      IgG antibodies were positive. She was treated with 30 mg/kg of intravenous
      methylprednisolone (3 days), 30 mg of oral prednisone (3 days), and tapering for
      8 weeks. Intravenous acyclovir was given for 10 days, followed by oral acyclovir
      for 4 months. Aspirin (100 mg/day) was given for 4 months. RESULTS: At 12 months,
      the girl felt good. Her right eye acuity was 6/9, with an intraocular pressure of
      17 mm Hg. The peripheral retina showed scarring but no detachment. CONCLUSIONS:
      This is the first report of a once-daily high-dose methylprednisolone pulse
      therapy in one of the youngest known ARN cases. Pulsed steroid therapy was based
      on its known effectiveness in vasculitis, which is the main pathophysiology in
      ARN. There was no evidence of steroid-related viral over-replication. Our case
      achieved an excellent clinical and ophthalmic recovery in spite of the poor
      prognosis. The positive result of this case report provides a basis for further
      evaluation of high-dose steroid pulse therapy in ARN.

PMID- 24932180
TI  - Primary Multiple Simultaneous Intracerebral Hemorrhages between 1950 and 2013:
      Analysis of Data on Age, Sex and Outcome.
AB  - BACKGROUND: Primary multiple simultaneous intracerebral hemorrhages (MSICHs) are
      quite rare. Although occasional reports have been found, there have been no
      systematic reviews. The published case reports and case series contain
      overlapping data, leading to erroneous information about MSICHs. This is the
      first extensive review of accessible studies published in English on MSICHs. Our
      primary objective was to analyze the demographic data on age, sex, outcome and
      prognosis with regard to primary MSICHs. SUMMARY: A PubMed search without
      language restriction for articles with results from human studies and registered
      between January 1950 and September 2013 yielded 677 articles. The following
      inclusion criteria were applied: (1) reported case(s) or case series on primary
      MSICHs; (2) text partly or fully in English, and (3) text contains identifiable
      data on age, sex and outcome of patients. A total of 24 articles met all the
      inclusion criteria. The reference lists of these 24 articles were inspected for
      additional relevant articles, which yielded another 20 articles. In all, 248
      cases were identified; 143 cases were excluded for various reasons: 52 duplicate
      cases, 18 cases of multiple nonsimultaneous intracerebral hemorrhages, 25 cases
      of secondary MSICHs, and 48 cases with incomplete data on age, sex and outcome.
      The remaining 105 cases were analyzed. MSICHs were found to be more common in
      bilateral cases (53.33%): there were bilateral basal ganglia hemorrhages
      (33.33%), bilateral thalamic hemorrhages (18.10%), bilateral lobar hemorrhages
      (0.95%) and bilateral cerebellar hemorrhages (0.95%). Nonbilateral MSICHs were
      found in 46.67% of the cases. The hematomas were commonly distributed in the
      basal ganglia (45.83%), thalamus (30.56%) and cerebellum (10.19%). MSICHs were
      more frequently encountered in males (60.95%; average age: 59.13 +/- 12.49
      years). The average age of the female patients was higher (63.89 +/- 13.11
      years). Patients with primary MSICHs had a survival rate of 56.20%. There was a
      favorable outcome of primary MSICHs in 18.10% of all the cases, the highest
      proportion of which was in the nonbilateral MSICH group. The remaining 38.10% had
      unfavorable outcomes. Death occurred in 43.80% of all cases, the highest
      proportion being found in the bilateral basal ganglia hemorrhage group. Primary
      MSICHs share features with solitary intracerebral hemorrhage regarding age, sex,
      and the location and distribution of hematomas, but they have a poorer outcome (p
      < 0.05). KEY MESSAGES: Primary MSICHs are rare and share features with solitary
      intracerebral hemorrhage regarding age and the location and distribution of
      hematomas. Patients have a poorer prognosis but higher favorable outcome rates in
      case of survival. This information adds to the awareness of clinicians that
      higher rates of favorable outcomes can be achieved for MSICHs.

PMID- 24932181
TI  - Effectiveness of montelukast administered as monotherapy or in combination with
      inhaled corticosteroid in pediatric patients with uncontrolled asthma: a
      prospective cohort study.
AB  - BACKGROUND: Asthma is the most common chronic disease of childhood and a leading
      cause of childhood morbidity. The aim of the current study was to assess the
      effectiveness of montelukast administered as monotherapy or in combination with
      current inhaled corticosteroids (ICS) in pediatric patients with uncontrolled
      asthma as per the Canadian Asthma Consensus Guidelines. METHODS: Twelve-week,
      multicentre, open-label, observational study. Primary effectiveness outcome was
      the proportion of patients achieving asthma control (Asthma Control Questionnaire
      (ACQ) score <=0.75) at weeks 4 and 12. RESULTS: A total of 328 patients with
      uncontrolled asthma (ACQ > 0.75) were enrolled with mean +/- SD age of 6.9 +/-
      3.4 years. Among these, 76 (23.2%) were treated with montelukast monotherapy and
      252 (76.8%) with montelukast combined with ICS. By 4 weeks of treatment 61.3% and
      52.9% of the patients in the monotherapy and combination group, respectively,
      achieved asthma control. These proportions increased to 75.0% and 70.9%,
      respectively, at 12 weeks. Within the monotherapy group, clinically significant
      improvements in the ACQ score (mean +/- SD of 1.67 +/- 0.69, 0.71 +/- 0.70 and
      0.50 +/- 0.52 at baseline, 4 and 12 weeks, respectively; p < 0.001) and the
      PACQLQ score (mean +/- SD of 5.34 +/- 1.14, 6.32 +/- 0.89 and 6.51 +/- 0.85 at
      baseline, 4 and 12 weeks, respectively; p < 0.001) were observed. In the
      combination group, the mean +/- SD ACQ score significantly improved from 2.02 +/-
      0.83 at baseline to 0.90 +/- 0.86 at 4 weeks and 0.64 +/- 0.86 at 12 weeks (p <
      0.001), while the PACQLQ score improved from 4.42 +/- 1.35 at baseline to 5.76 +/
      1.30 at 4 weeks and 6.21 +/- 1.03 at 12 weeks (p < 0.001). After a 12-week
      montelukast add-on therapy, 22.6% of patients reduced their ICS dosage. Similar
      results were observed among preschool- and school-aged patients. CONCLUSIONS:
      Montelukast as monotherapy or in combination with ICS represents an effective
      treatment strategy for achieving asthma control in pediatric patients and
      improving caregivers' quality of life. TRIAL REGISTRATION: This study is
      registered at ClinicalTrial.gov: NCT00832455.

PMID- 24932183
TI  - Nitrogen containing bisphosphonates associated osteonecrosis of the jaws: A
      review for past 10 year literature.
AB  - Nitrogen containing bisphosphonate (N-BP) therapy is used extensively to treat
      osteoporosis and osteolytic bone lesions. Recently, a special form of
      osteonecrosis limited to the maxillofacial skeleton has been discovered
      especially within those patients who are receiving either long-term N-BP therapy
      alone and/or associated with invasive dental procedure. Bisphosphonates
      accumulate almost exclusively in maxillofacial skeleton owing to high bone turn
      over remodeling to maintain the mechanical competence. The pathogenesis and why
      it commonly appears in maxillofacial skeleton and the fixed treatment strategies
      remains unknown. The aim of this study was to improve the clinician understanding
      of N-BPs associated osteonecrosis of maxillofacial skeleton by reviewing the past
      10 year literature. 

PMID- 24932182
TI  - Epigenetic regulation of asthma and allergic disease.
AB  - Epigenetics of asthma and allergic disease is a field that has expanded greatly
      in the last decade. Previously thought only in terms of cell differentiation, it
      is now evident the epigenetics regulate many processes. With T cell activation,
      commitment toward an allergic phenotype is tightly regulated by DNA methylation
      and histone modifications at the Th2 locus control region. When normal epigenetic
      control is disturbed, either experimentally or by environmental exposures,
      Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to
      daughter cells with cell replication but they can also be inherited through
      generations. In animal models, with constant environmental pressure,
      epigenetically determined phenotypes are amplified through generations and can
      last up to 2 generations after the environment is back to normal. In this review
      on the epigenetic regulation of asthma and allergic diseases we review basic
      epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then
      cover the transgenerational inheritance model of epigenetic traits and discuss
      how this could relate the amplification of asthma and allergic disease prevalence
      and severity through the last decades. Finally, we discuss recent epigenetic
      association studies for allergic phenotypes and related environmental risk
      factors as well as potential underlying mechanisms for these associations. 

PMID- 24932185
TI  - Do dental stem cells depict distinct characteristics? - Establishing their
      "phenotypic fingerprint".
AB  - Dental tissues provide an alternate source of stem cells compared with bone
      marrow and have a similar potency as that of bone marrow derived mesenchymal stem
      cells. It has been established there are six types of dental stem cells: Dental
      pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells
      from apical papilla, periodontal ligament stem cells, dental follicle progenitor
      cells, oral periosteum stem cells and recently gingival connective tissue stem
      cells. Most of the dental tissues have a common developmental pathway; thus, it
      is relevant to understand whether stem cells derived from these closely related
      tissues are programmed differently. The present review analyzes whether stem
      cells form dental tissues depict distinct characteristics by gaining insight into
      differences in their immunophenotype. In addition, to explore the possibility of
      establishing a unique phenotypic fingerprint of these stem cells by identifying
      the unique markers that can be used to isolate these stem cells. This, in future
      will help in developing better techniques and markers for identification and
      utilization of these stem cells for regenerative therapy. 

PMID- 24932184
TI  - Periodontio-integrated implants: A revolutionary concept.
AB  - Though the fields of regenerative dentistry and tissue engineering have undergone
      significant advancements, yet its application to the field of implant-dentistry
      is lacking; in the sense that presently the implants are being placed with the
      aim of attaining osseointegration without giving consideration to the
      regeneration of periodontium around the implant. The following article reveals
      the clinical benefits of such periodontio-integrated implants and reviews the
      relevant scientific proofs. A comprehensive research to provide scientific
      evidence supporting the feasibility of periodontio-integrated implants was
      carried out using various online resources such as PubMed, Wiley-Blackwell,
      Elsevier etc., to retrieve studies published between 1980 and 2012 using the
      following key words: "implant," "tissue engineering," "periodontium," "osseo
      integration," "osseoperception," "regeneration" (and their synonyms) and it was
      found that in the past three decades, several successful experiments have been
      conducted to devise "implant supported by the periodontium"that can maintain
      form, function and potential proprioceptive responses similar to a natural tooth.
      Based on these staunch evidences, the possibility of the future clinical use of
      such implant can be strongly stated which would revolutionize the implant
      dentistry and will be favored by the patients as well. However, further studies
      are required to validate the same. 

PMID- 24932186
TI  - Immunohistochemical analysis of Langerhans cells in chronic gingivitis using anti
      CD1a antibody.
AB  - BACKGROUND: The Langerhans cells (LCs) are dendritic cells (DCs) which belong to
      the group of antigen presenting cells (APCs). Their function is to recognize the
      antigen, capture it, and present it to the T lymphocytes; thus initiating an
      early immune response. The antigen presenting functional LCs may play an
      important part in initiation and development of gingivitis. The aim of this study
      was to analyze the density, intraepithelial distribution, and morphology of LCs
      in gingival epithelium among different age groups with chronic gingivitis and to
      compare it with that of normal gingiva. MATERIALS AND METHODS:
      Immunohistochemistry (IHC) was performed to study LCs in normal gingival
      epithelium (n = 10) and gingival epithelium in chronic gingivitis (n = 30) using
      anti-CD1a antibody. Mann Whitney U test was performed to compare the density of
      LCs in normal gingiva with chronic gingivitis. The distribution of LCs in various
      layers of the epithelium within the three age groups was analyzed using Kruskal
      Wallis test. P value less than 0.05 was considered as significant. RESULTS: The
      density of LCs in chronic gingivitis was significantly higher then that of normal
      gingiva. Comparing different age groups, the younger individuals had more number
      of LCs which were located in the superficial layers of gingival epithelium. In
      chronic gingivitis, higher number of LCs were located in deeper layers when
      compared with that of normal gingiva. Three morphological types of CD1a positive
      LCs were observed in normal gingiva, out of which the density of LCs with
      branched dendritic processes was highest in normal gingiva. CONCLUSION: The LCs
      showed variable number, location, and morphology which indicated their adaptation
      for function in chronic gingivitis.

PMID- 24932187
TI  - Oxidant-antioxidant status in tissue samples of oral leukoplakia.
AB  - BACKGROUND: Imbalances between the oxidant-antioxidant status have been
      implicated in the pathogenesis of several diseases, including oral cancer.
      Majority of oral cancer are preceded by a well-recognized group of pre-malignant
      lesions. However, only a small fraction of those lesions, undergo malignant
      transformation. Hence, there is a great need to identify biological markers,
      which will assist in identifying lesion carrying high-risk. This study aims to
      evaluate and compare the status of oxidative stress and antioxidant enzymes in
      tissue samples of patients with various clinicopathological stages of oral pre
      malignancy. MATERIALS AND METHODS: A case control study consisting of 20 new
      histopathologically proven leukoplakia patients and equal number of age, sex, and
      habit matched healthy subjects were recruited for this study. Their tissue
      samples were subjected to evaluation of lipid peroxidation product,
      thiobarbituric acid reactive substances and antioxidant enzymes, namely,
      superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and
      glutathione peroxidase (GPx) using spectrophotometric methods. The data are
      expressed as mean +/- standard deviation. The statistical comparisons were
      performed by independent Student's unpaired t-test and one-way analysis of
      variance. Pearson's correlation was performed for the biochemical parameters
      within the group and between the groups. For statistically significant
      correlations, simple linear regression was performed. P- value < 0.05 was
      considered statistically significant. RESULTS: Significant reduction in lipid
      peroxidation (P < 0.001) SOD and CAT (P < 0.001) was observed in the tissue of
      leukoplakia patients as compared to the healthy controls. On the other hand, GSH
      and GPx were significantly increased in tumor samples. CONCLUSION: Reduced lipid
      peroxidation and increased activity of GSH and GPx provides the suitable
      environment for the tumor growth and malignant transformation in the later
      stages. Among the antioxidant enzymes, glutathione reductase appears to have a
      profound role in carcinogenesis.

PMID- 24932188
TI  - Mast cell count in oral reactive lesions: A histochemical study.
AB  - BACKGROUND: The aim of this study was to quantify the number of mast cells in
      focal reactive hyperplastic lesions of the oral cavity and to compare these two
      number of mast cells in normal gingival tissues and to correlate their presence
      with the state of connective tissue changes in reactive lesions and probably
      suggest a role for mast cells in these lesions. MATERIALS AND METHODS: Patient
      records were retrieved during a 10 year period from 2001 to 2010. Data of all
      reactive hyperplasias namely focal fibrous hyperplasia, pyogenic granuloma (PG),
      peripheral ossifying fibroma (POF) and peripheral giant cell granuloma (PGCG)
      were reviewed and 10 cases seen in the gingiva were selected for each category
      and stained with 1% toluidine blue for mast cells. Statistical analysis was
      applied to see the significant differences between the groups and with the normal
      gingival tissue. One-way ANOVA-F and unpaired t-test was applied and significant
      differences were seen between the groups at 5% level of significance. RESULTS: In
      this study, mast cell count was maximum in POF and fibrous hyperplasia (FH)
      followed by cases of PG and PGCG. CONCLUSION: The number of mast cells was more
      numerous in POF and FH suggesting that mast cell activation is a characteristic
      feature of chronic inflammation, a condition that may lead to fibrosis as a
      result of increased collagen synthesis by fibroblasts.

PMID- 24932189
TI  - Combined effects of Er: YAG laser and casein phosphopeptide-amorphous calcium
      phosphate on the inhibition of enamel demineralization: An in vitro study.
AB  - BACKGROUND: Development of white spot lesions on enamel is a significant and
      common problem during the fixed orthodontic treatment. Various preventive methods
      have been suggested. The purpose of this study was to evaluate the preventive
      potential of MI Paste Plus, Er: YAG Laser and combined under similar in vitro
      conditions against demineralization. MATERIALS AND METHODS: In this experimental
      in vitro study, 60 extracted premolars were randomly allocated to four groups (n
      = 15) of control, MI Paste Plus, Laser and MI + Laser (MIL). Enamel surface of
      each group was treated with one of above materials before and during the pH
      cycling for 12 days through a daily procedure of demineralization and
      remineralization for 3 h and 20 h, respectively. Teeth were sectioned and
      evaluated quantitatively by cross-sectional microhardness testing at 20 MUm
      intervals from the outer enamel surface toward dentinoenamel junction up to 160
      MUm and data were analyzed using the one-way analysis of variance and Tukey test.
      P < 0.05 was considered as significant. RESULTS: MIL group had the least amount
      of demineralization (P < 0.001). Control group (C group) had the greatest
      relative mineral loss and the laser group (L group) had 45% less mineral loss
      than the C group and there was no significant difference between the MI Paste
      Plus and L group (P = 0.154). CONCLUSION: BASED ON THESE RESULTS, ER: YAG laser
      was able to decrease demineralization and was a potential alternative to
      preventive dentistry and was more effective when combined with casein
      phosphopeptide-amorphous calcium phosphate products.

PMID- 24932190
TI  - Histological evaluation of pulp tissue from second primary molars correlated with
      clinical and radiographic caries findings.
AB  - BACKGROUND: Managing dental caries in young children is demanding due to the
      elusions present on the right diagnostic criteria for treatment. The present
      study evaluated the histological status of pulp tissues extracted from primary
      second molar with caries involvement. Histological findings are correlated with
      clinical and radiographic assessment. MATERIALS AND METHODS: Simple experimental
      study was conducted on upper or lower second primary molars with occlusal (22
      teeth) or proximal (22 teeth) dental caries. Selected children were below 6 years
      of age. Percentage of caries involvement, residual dentin thickness (RDT),
      radiographic assessment of interradicular and periapical areas, clinical caries
      depth and signs and symptoms are the parameters considered for comparing with the
      histological findings. The specimens were grouped based on the nature of the
      inflammatory process as acute or chronic. The data were analyzed by Student t
      test to compare histological types of inflammation with clinical parameters. P
      value < 0.05 was considered as significant. RESULTS: Four cases revealed severe
      acute inflammation in coronal and relatively mild acute inflammation in radicular
      pulp. In the rest of the specimen coronal and radicular pulp had similar acute or
      chronic inflammatory changes. Histological evidence of pulpitis correlated with
      dental caries depth of >=80%, RDT of <=1 mm, radiographic rarefactions in the
      interradicular regions and symptoms of pain. CONCLUSION: Primary second molars
      with more than two-third caries involvement with symptoms of pain histologically
      showed inflammation of both coronal and radicular pulp tissues in all cases.

PMID- 24932191
TI  - Detection of oral squamous cell carcinoma metastasis with cathepsin D: An
      immunohistochemical approach.
AB  - BACKGROUND: The lysosomal protease cathepsin D (CD) has been associated with
      tumor progression in malignant tumors including oral squamous cell carcinoma
      (OSCC). The purpose of this study was to find out any association between the CD
      and lymph node metastasis and to study the correlation of CD with various
      clinicopathological parameters to aid in assessment of its role as a prognostic
      indicator. MATERIALS AND METHODS: Immunohistochemical staining was performed on
      20 OSCC samples with polyclonal antibody against CD. Positive results indicative
      of the presence of CD were further analyzed to determine any correlation between
      the CD and other clinicopathological parameters. Pearson Chi-square analyses,
      Spearsman correlation coefficient, Mann-Whitney test, Kruskal Wallis test and
      student t test were used for statistical analysis (P < 0.05). RESULTS: Patients
      with lymph node metastasis showed statistically significant increase in CD
      expression (P < 0.01). Increasing tumor size seemed to correlate with increased
      CD expression (P < 0.05). CONCLUSION: Based on its association with other
      clinicopathological variables, CD expression can be used for the assessment of
      patient survival in cases of OSCC.

PMID- 24932192
TI  - Efficiency of systemic versus intralesional bone marrow-derived stem cells in
      regeneration of oral mucosa after induction of formocresol induced ulcers in
      dogs.
AB  - BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are the key to
      regenerative wound healing. MSCs have spatial memory and respond to local
      environment. The goal of this study was to evaluate the use of systemic and
      intralesional transplantation of BMSCs for regeneration of oral mucosa in an in
      vivo dog model. MATERIALS AND METHODS: Transplantation of undifferentiated green
      fluorescent protein (GFP)-labeled autologous BMSCs systemically, submucosally or
      vehicle (saline) was injected around the chemically induced oral ulcer in each
      group of 18 adult dogs. The healing process of the ulcer was monitored clinically
      and histopathologically. Gene expression of vascular endothelial growth factor
      (VEGF) and collagen genes was detected in biopsies from all ulcers. One way ANOVA
      was used to compare between means of the three groups. Results were considered
      significant at P < 0.05. RESULTS: Flow cytometric analysis of the MSCs at the
      passage 3 showed that these cells were negative for CD45 (2.39%). They expressed
      high levels of CD29 (98.34%). Frozen fluorescence microscopy of sections of the
      cell-treated oral tissue of all groups indicated that the GFP-transduced
      implanted cells were integrated within the transplanted tissues. The treatment
      resulted in dramatic wound edge activation and resurfacing of oral mucosa wound.
      CONCLUSION: Our results revealed that BMSCs may be labeled with (GFP), in order
      to know the distribution of these cells after administration, and suggest that
      intralesional administration is an appropriate procedure to achieve acceptable
      regeneration of the previously injured oral mucosa more than systemic route.

PMID- 24932193
TI  - Apical sealing ability of resilon/epiphany system.
AB  - BACKGROUND: Endodontic leakage research focus mainly on the quality of the apical
      seal of the root canal system and the newly introduced resilon/epiphany system
      claim to be superior to Gutta-percha in respect to obturation procedure. The aim
      of this study is to evaluate the root canal obturation completed by
      resilon/epiphany system. MATERIALS AND METHODS: A total of 42 teeth were selected
      and were divided into four groups. Two experimental groups consisted of 15 teeth
      each and positive control group consisted of eight teeth and negative control
      group consisted of four teeth. In the experimental groups, Group 1 was obturated
      with resilon/epiphany system and Group 2 was obturated with Gutta-percha and
      endofil sealer by lateral condensation technique. The teeth were then immersed in
      Methelene blue solution and were split longitudinally to access the amount of dye
      penetrated in the canal. The specimens were viewed under scanning electron
      microscope to evaluate the adhesion of the obturating material to the root canal
      walls. Data was subjected to statistical analysis by Analysis of Variance and
      Bonferroni multiple comparison test at 1% level of significance. RESULTS: The
      resilon/epiphany system showed better adaptation to the root canal walls, but the
      difference in dye penetration was not statistically significant when compared to
      specimens obturated with Gutta-percha and endofil sealer. CONCLUSION: Although,
      there was no statistically significant difference between the groups, but
      resilon/epiphany system showed better adaptation to the root canal walls.

PMID- 24932194
TI  - Evaluation of the efficacy of taurine as an antioxidant in the management of
      patients with chronic periodontitis.
AB  - BACKGROUND: In the recent years, various studies have shown a link between the
      free radicals, antioxidants and periodontal diseases. The purpose of the present
      study was to evaluate the oxidative stress and the antioxidant status present in
      the gingival tissue and plasma of patients with chronic periodontitis and to
      evaluate the antioxidant property of taurine. MATERIALS AND METHODS: Periodontal
      status in 10 chronic periodontitis patients was assessed in terms of gingival
      index, plaque index, probing pocket depth and clinical attachment level prior to
      and after oral administration of taurine (500 mg O.D.) for 15 days. The oxidative
      stress present in the gingival tissue and blood (by measuring thiobarbituric acid
      reactive substance [TBARS]) and the antioxidants namely glutathione peroxidase
      (GPX) and reduced glutathione (GSH) were estimated before and after
      administration of taurine. The changes in the clinical parameters were also
      reassessed following administration of taurine. Statistical comparisons were
      performed using the Student's t-test. A level of P < 0.05 was considered as
      statistically significant. RESULTS: The levels of TBARS in plasma and gingival
      tissue showed a significant reduction (P < 0.001) following administration of
      taurine. The antioxidant enzyme GPX showed a significant reduction following
      administration of taurine (P < 0.001), whereas GSH increased significantly (P <
      0.001) following administration of taurine. The improvement in the periodontal
      status following administration of taurine was also significant statistically.
      CONCLUSION: Based on the biochemical and clinical assessments, taurine seems to
      exert a protective role against the oxidative stress in the management of
      patients with chronic periodontitis.

PMID- 24932195
TI  - Evaluation of load-deflection properties of fiber-reinforced composites and its
      comparison with stainless steel wires.
AB  - BACKGROUND: The aim of this study was to evaluate the response of common sized
      fiber-reinforced composites (FRCs) to different deflections due to bending forces
      and comparing it with stainless steel (SS) wires. MATERIALS AND METHODS: In this
      experimental study, two FRC groups with 0.75 mm and 1.2 mm diameters (Everstick
      Ortho, Stick Tech, Finland) and three SS groups with 0.016 * 0.022 inch, 0.0215 *
      0.028 inch and 0.7 mm diameters (3M Uniteck, Monrovia, California, USA) were
      tested. Each group contained 10 samples that were tested according to a three
      point bending test. Each group was tested at deflections of 0.5, 1 and 1.5 mm and
      the data was analyzed using the repeated measure ANOVA by SPSS software
      (Statistical Package for the Social Sciences, IBM SPSS, Inc. in Chicago,
      Illinois, USA). P < 0.05 was considered as significant. RESULTS: The highest
      recorded load belonged to the 1.2 mm FRC and after that 0.7 mm SS wire, 0.75 mm
      FRC, 0.0215 * 0.028 inch SS wire and finally 0.016 * 0.022 inch SS wire. The 0.7
      mm SS wire and 0.75 mm FRC were compared as retainers and the results showed the
      0.7 mm SS wire showed significantly higher load compared with 0.75 mm FRC (P <
      0.05). The 1.2 mm FRC had significantly higher load compared to 0.0215 * 0.028
      inch and 0.016 * 0.022 inch SS wires (P < 0.05). CONCLUSION: The results showed
      that the 1.2 mm FRC group had significantly higher load compared to SS wires and
      other FRC groups under the 0.5, 1 and 1.5 mm deflections. Therefore, it can be
      suggested that FRC can be used as an esthetic replacement for SS wires for active
      and passive purposes in orthodontics.

PMID- 24932196
TI  - A comparative study of Candida albicans mean colony counts and blood group
      antigens in the saliva of healthy subjects.
AB  - BACKGROUND: Candida albicans is the most common opportunistic fungal species in
      the oral cavity. Various factors associated with C. albicans infection have been
      evaluated so far. In some studies, the relationship between the blood group
      antigens and C. albicans has been discussed. The aim of this study was to assess
      mean C. albicans colony counts in the saliva of healthy subjects and its
      relationship with ABO blood groups. MATERIALS AND METHODS: This cross
      sectional/analytical study was performed in the Oral Medicine Department, School
      of Dentistry, Isfahan University of Medical Sciences. Unstimulated whole saliva
      samples were obtained from 300 healthy subjects, including 100 individuals with
      blood group O, 100 with blood group A and 100 with blood group B. The samples
      were cultured on Sabouraud's dextrose agar media to determine the means of C.
      albicans colonies. Data were analyzed by Kruskal-Wallis and Mann-Whitney
      statistical tests and SPSS 16. Statistical significance was defined at P < 0.05.
      RESULTS: The samples included 156 males and 144 females with a mean age of 27.52
      years. The mean colony counts in the saliva of individuals with blood groups O,
      A, and B were 26.4, 19.84, and 21.23, respectively. There were no significant
      differences between the three groups (P = 0.280). CONCLUSION: Although the mean
      C. albicans colony counts in individuals with blood group O were more than those
      with other blood groups, the differences were not statistically significant. More
      research studies are needed in order to prove the role of blood groups in
      susceptibility to candidiasis.

PMID- 24932197
TI  - A modified efficient method for dental pulp stem cell isolation.
AB  - BACKGROUND: Dental pulp stem cells can be used in regenerative endodontic
      therapy. The aim of this study was to introduce an efficient method for dental
      pulp stem cells isolation. MATERIALS AND METHODS: In this in-vitro study, 60
      extracted human third molars were split and pulp tissue was extracted. Dental
      pulp stem cells were isolated by the following three different methods: (1)
      digestion of pulp by collagenase/dispase enzyme and culture of the released
      cells; (2) outgrowth of the cells by culture of undigested pulp pieces; (3)
      digestion of pulp tissue pieces and fixing them. The cells were cultured in
      minimum essential medium alpha modification (alphaMEM) medium supplemented with
      20% fetal bovine serum(FBS) in humid 37 degrees C incubator with 5% CO 2. The
      markers of stem cells were studied by reverse transcriptase polymerase chain
      reaction (PCR). The student t-test was used for comparing the means of
      independent groups. P <0.05 was considered as significant. RESULTS: The results
      indicated that by the first method a few cell colonies with homogenous morphology
      were detectable after 4 days, while in the outgrowth method more time was needed
      (10-12 days) to allow sufficient numbers of heterogeneous phenotype stem cells to
      migrate out of tissue. Interestingly, with the improved third method, we obtained
      stem cells successfully with about 60% efficiency after 2 days. The results of RT
      PCR suggested the expression of Nanog, Oct-4, and Nucleostemin markers in the
      isolated cells from dental pulps. CONCLUSION: This study proposes a new method
      with high efficacy to obtain dental pulp stem cells in a short time.

PMID- 24932198
TI  - Evaluation of isthmus prevalence, location, and types in mesial roots of
      mandibular molars in the Iranian Population.
AB  - BACKGROUND: Management of canal isthmus is considered as an important factor for
      successful endodontic treatment. Accordingly, this study was designed to
      determine the prevalence, location, and types of isthmus in mesial root canals of
      extracted mandibular molars in a sample of Iranian population. MATERIALS AND
      METHODS: In this cross-sectional descriptive study, 60 extracted molars with two
      mesial canals were included. The samples were initially decoronated and then,
      roots were sectioned horizontally at 2, 4, and 6 mm levels from the apex via a
      low-speed handpiece with a thin metallic disk and finally prepared and stained
      with Indian ink. All sections were examined using a stereomicroscope at a
      magnification of *30. Prevalence, location, and types of isthmus were evaluated
      based on the classifications by Kim and Teixeira and all data were statistically
      analyzed by the chi-squared test. The statistical significance level was
      established at 0.05. RESULTS: Eighty-three percent of extracted mandibular molars
      had an isthmus at the mesial root. This prevalence increased with distance from
      the apex, that is, 92% at 6 mm from the apex and 70% at 2 mm from the apex. A
      statistically significant difference was found between the sections at 2 and 6 mm
      from the apex (P < 0.05), but no other significant differences between other
      levels (P > 0.05). CONCLUSION: Isthmus is very common in the mesial roots of the
      mandibular permanent molars in the Iranian population, with the highest
      prevalence in the 6 mm distance from the root apex. Therefore, detection,
      cleaning, and filling of these apical 6 mm isthmuses are of great benefit in
      modern endodontics.

PMID- 24932199
TI  - Immunohistochemical analysis of B-cell lymphoma -2 in pleomorphic adenoma and
      mucoepidermoid carcinoma.
AB  - BACKGROUND: Salivary gland tumors form a major area in the field of oral
      pathology. B-cell lymphoma -2 (Bcl-2) is an anti-apoptotic gene with up
      regulation in various neoplasms. The aim of the present case-control study was to
      comparatively investigate the expression of Bcl-2 protein in pleomorphic adenoma
      (PA) and mucoepidermoid carcinoma (MEC) and assess its potential diagnostic role
      in differentiating these tumors. MATERIALS AND METHODS: A total of 28 cases (18
      specimens of PA [control] and 10 blocks of MEC [case]) were selected for analysis
      by streptavidin-biotin peroxidase method with antibody against Bcl-2. The
      percentage of positive cells was calculated from a minimum of 1000 neoplastic
      cells and H-score was identified (% positive cells * intensity of staining). Data
      were analyzed using two-way ANOVA, t-test, Spearman, Chi-square and Fisher tests
      (alpha = 0.05). RESULTS: bcl-2 expression was shown in 13 cases (71%) of PA and 3
      cases (30%) of MEC. In addition, four cases of PA showed strong staining. There
      was a significant difference between the expression intensity of Bcl-2 in the two
      tumors (P = 0.048) according to ANOVA. No correlation was observed between Bcl-2
      expression with the size and location of tumors (P > 0.05). CONCLUSION: Bcl-2
      expression might be used for differentiating these tumors. Bcl-2 protein was
      overexpressed in PA compared with MEC. Hence, it seems that unlike what was
      observed in PA, Bcl-2 probably does not participate in the pathogenesis of MEC.

PMID- 24932200
TI  - Fracture resistance of structurally compromised premolar roots restored with
      single and accessory glass or quartz fiber posts.
AB  - BACKGROUND: Glass and quartz fiber posts are used in restoration of structurally
      compromised roots. Accessory fiber posts are recently introduced to enhance the
      fiber post adaptation. This study evaluated the effectiveness of glass versus
      quartz accessory fiber posts. MATERIALS AND METHODS: In this experimental study,
      40 mandibular premolar roots with similar dimension (radius of 3.5 +/- 0.2 mm and
      length of 13 +/- 0.5 mm) were selected and their root canals were flared until
      1.5 mm of dentin wall remained. They were randomly assigned to four groups (n =
      10) and restored as follows: Exacto glass fiber post (EX), Exacto glass fiber
      post + 2 Reforpin accessories (EXR), D. T. Light quartz fiber post (DT), and D.
      T. Light quartz fiber post + 2 Fibercone accessories (DTF). All posts were
      cemented with Duo-Link resin cement and the cores were built with the particulate
      filler composite. Following 1-week water storage, specimens were subjected to
      fracture loads in a universal testing machine. The maximum loads and failure
      modes were recorded and analyzed with the two-way analysis of variance (ANOVA)
      and Fisher's exact tests (alpha = 0.05). RESULTS: The mean fracture resistance
      values (N) were 402.8 (EX), 378.4 (EXR), 400.1 (DT), and 348.5 (DTF). Two-way
      ANOVA test showed neither reinforcing method (P = 0.094), nor post composition (P
      = 0.462) had statistically significant differences on fracture resistance of the
      structurally compromised premolar teeth. Fisher's exact test also demonstrated no
      statistically significant difference regarding two variables (P = 0.695). Core
      fracture was the most common failure mode (62.5%). CONCLUSION: Glass and quartz
      fiber posts with or without accessories restored the weakened premolar roots
      equally.

PMID- 24932201
TI  - A multilocular radiolucency of mandible as the first evidence of multiple
      myeloma: A clinico-radiographic case report.
AB  - The incidence of multiple myeloma (MM) affecting the jaws is 30% and on rare
      occasions the oral involvement can be the first indication of the disease.
      Authors report a case of MM in a 40-year-old woman who presented with a
      multilocular radiolucent lesion in the left mandible initially mistaken as an
      ameloblastoma. Conventional radiographs revealed a multilocular lesion on the
      molar region. Computed tomography (CT) and 3 dimensional CT revealed lytic, space
      occupying lesion perforating the inferior cortex. Magnetic resonance imaging
      (MRI) revealed a hypointense lesion on T1 weighted image and hyperintense lesion
      on T2 weighted image. Histopathological and lab investigations lead to the
      diagnosis of MM. MRI is superior in depicting the size of the lesion as compared
      to CT and conventional radiographs. 

PMID- 24932202
TI  - Prosthodontic management of a patient with Gardner's syndrome: A clinical case
      report.
AB  - Gardner's syndrome is a genetic condition demonstrating an autosomal dominant
      trait and characterized by the multiple colonic polyps (familial adenomatous
      polyposis coli) with sebaceous cysts and jaw osteomas. Various dental
      abnormalities present in patient's suffering with this syndrome includes multiple
      impacted or unerupted teeth, supernumerary teeth, hypodontia, compound odontomes
      and dentigerous cyst. In this case report, a patient with Gardner's syndrome who
      suffered from functional and psychological problems owing to multiple impacted,
      unerupted teeth and hypodontia was presented. Patient was treated with a
      maxillary conventional overdenture opposing mandibular custom bar supported
      overdentures. 

PMID- 24932203
TI  - Pediatric cervicofacial actinomycosis disclosing an underlying congenital dermoid
      cyst.
AB  - Pediatric cervicofacial actinomycosis is a rare occurrence consequent to dental
      infections and manipulations or maxillofacial trauma. The clinical presentation
      ranges from multiple draining sinuses to swellings resembling tumors and cysts.
      The present unusual case had congenital dermoid cyst of mid upper lip with
      Actinomyces israelii infection identified on microscopy, culture, and
      histopathology. A successful outcome in the present case was obtained using
      combination of medical and surgical treatment. 

PMID- 24932204
TI  - Juvenile fibromatosis of the temporomandibular joint: A rare case report.
AB  - Fibromatosis is the non-malignant proliferation of fibroblasts that aggressively
      invade adjacent tissues. It is composed of well-differentiated cells separated by
      considerable collagen and/or reticulin. The cause of this abundant growth is
      unknown, but many suspect hormonal or traumatic influences. When fibromatosis
      develops in the temporomandibular joint (TMJ) or adjoining tissues, its
      aggressive growth can compress the trachea and cause death. The management is
      difficult as it is perplexing to comprehend. Resection is the treatment of
      choice. The following case report presents a rare case of fibromatosis involving
      TMJ and its uneventful successful management. 

PMID- 24932205
TI  - On the authorship criteria.

PMID- 24932208
TI  - A virus-induced gene silencing (VIGS) system for functional genomics in the
      parasitic plant Striga hermonthica.
AB  - BACKGROUND: Striga hermonthica is a hemiparasitic weed that infects cereals in
      Sub Sahara Africa (SSA) resulting in up to 100% grain yield loss. This
      significant loss in grain yields is a major contributor to food insecurity and
      poverty in the region. Current strategies to control the parasite are costly,
      unavailable and remain unpracticed by small-scale farmers, underscoring the need
      for more economical and sustainable control strategies. Development of resistant
      germplasm is the most sustainable strategy in the control of S. hermonthica, but
      is constrained by paucity of resistance genes for introduction into crop
      germplasm. RNA interference (RNAi) has potential for developing host-derived
      resistance against S. hermonthica by transformation of host crops with RNAi
      sequences targeted at critical Striga genes. The application of RNAi in
      management of S. hermonthica is however constrained by lack of efficient high
      throughput screening protocols for the candidate genes for silencing, as well as
      sub optimal delivery of siRNAs into the parasite. In comparison to stable
      transformation, viral induced gene silencing (VIGS) is a rapid and powerful tool
      for plant functional genomics and provides an easy and effective strategy in
      screening for putative candidate genes to target through RNAi. In addition, VIGS
      allows for a secondary amplification of the RNAi signal increasing the siRNA
      threshold and facilitates siRNA transport through viral movement proteins. We
      tested the efficiency of the Tobacco rattle virus (TRV1 and TRV2) VIGS vectors in
      silencing S. hermonthica phytoene desaturase (PDS) gene through agrodrench and
      agro-infiltration. RESULTS: We report the validation of VIGS in S. hermonthica
      using a silencing cassette generated from TRV with a PDS gene insert. Agro
      infiltrated and agro-drenched S. hermonthica leaves showed photo-bleaching
      phenotypes typical for PDS silencing within 7 and 14 days post infection
      respectively. In both cases S. hermonthica plants recovered from photo-bleaching
      effects within 28 days post inoculation. The transformation efficiency of the
      VIGS protocol in S. hermonthica was (60 +/- 2.9)%. CONCLUSION: These results
      demonstrate that the TRV-VIGS system work in S. hermonthica and can be used for
      candidate gene validation for their role in the parasite development and
      parasitism, with the ultimate goal of developing resistant transgenic maize.

PMID- 24932209
TI  - Evaluation of Compton gamma camera prototype based on pixelated CdTe detectors.
AB  - A proposed Compton camera prototype based on pixelated CdTe is simulated and
      evaluated in order to establish its feasibility and expected performance in real
      laboratory tests. The system is based on module units containing a 2*4 array of
      square CdTe detectors of 10*10 mm2 area and 2 mm thickness. The detectors are
      pixelated and stacked forming a 3D detector with voxel sizes of 2 * 1 * 2 mm3.
      The camera performance is simulated with Geant4-based Architecture for Medicine
      Oriented Simulations(GAMOS) and the Origin Ensemble(OE) algorithm is used for the
      image reconstruction. The simulation shows that the camera can operate with up to
      104 Bq source activities with equal efficiency and is completely saturated at 109
      Bq. The efficiency of the system is evaluated using a simulated 18F point source
      phantom in the center of the Field-of-View (FOV) achieving an intrinsic
      efficiency of 0.4 counts per second per kilobecquerel. The spatial resolution
      measured from the point spread function (PSF) shows a FWHM of 1.5 mm along the
      direction perpendicular to the scatterer, making it possible to distinguish two
      points at 3 mm separation with a peak-to-valley ratio of 8.

PMID- 24932207
TI  - Alcohol consumption and hormonal alterations related to muscle hypertrophy: a
      review.
AB  - Detrimental effects of acute and chronic alcohol (ethanol) consumption on human
      physiology are well documented in the literature. These adversely influence
      neural, metabolic, cardiovascular, and thermoregulatory functions. However, the
      side effects of ethanol consumption on hormonal fluctuations and subsequent
      related skeletal muscle alterations have received less attention and as such are
      not entirely understood. The focus of this review is to identify the side effects
      of ethanol consumption on the major hormones related to muscle metabolism and
      clarify how the hormonal profiles are altered by such consumption. 

PMID- 24932211
TI  - Burkitt lymphoma: epidemiological features and survival in a South African
      centre.
AB  - BACKGROUND: The epidemiology of Burkitt Lymphoma (BL) shows that the endemic type
      is mainly confined to equatorial Africa and has a very close association with the
      Epstein-Barr virus (EBV), while the sporadic variant shows only a 20% association
      with EBV and is seen mainly in Europe and North America. An immunodeficent form
      of BL has been described more recently. This study aimed to describe the
      epidemiological characteristics and survival of children presenting with BL to
      Tygerberg Hospital, Cape Town, in South Africa. METHODS: A retrospective,
      descriptive study reviewed all pediatric cases of Burkitt lymphoma at Tygerberg
      Hospital Oncology Unit between 1 January 1995 and 31 December 2010. The following
      data were analysed: age at diagnosis, gender, anatomic site, race, socio-economic
      demographic (rural vs. urban), treatment protocol, side effects, viral
      characteristics and survival. All cases were confirmed by histology and reviewed
      by a tumour board. RESULTS: A total of 51 patients with Burkitt lymphoma were
      analysed from 1995 to 2010. Their age ranged from 2 to 14 years (mean of 6.8
      years).The male to female ratio was 3.6/1. Most of the patients lived in an urban
      setting (52.9%). The initial presenting tumour site was abdominal in most cases
      (76.4%). The majority of patients (90%) were treated with the LMB protocol.
      Neutropenic sepsis, mucositis and gastroenteritis were the top 3 side effects
      while receiving therapy (58.8%, 50.9% and 31.3% respectively). The overall
      survival rate was 64.7%. A documented positive HIV1 test was found in 11% of the
      total number of patients. The stage of the disease at the time of presentation
      strongly influenced the outcome with only 41.6% of stage 4 patients surviving (p
      = 0.03). CONCLUSIONS: The patients seen at Tygerberg Hospital, South Africa
      presented typically with the sporadic variant of Burkitt Lymphoma. The patients
      presented with large abdominal masses and in an advanced stage of the disease.

PMID- 24932210
TI  - Nanoinformatics knowledge infrastructures: bringing efficient information
      management to nanomedical research.
AB  - Nanotechnology represents an area of particular promise and significant
      opportunity across multiple scientific disciplines. Ongoing nanotechnology
      research ranges from the characterization of nanoparticles and nanomaterials to
      the analysis and processing of experimental data seeking correlations between
      nanoparticles and their functionalities and side effects. Due to their special
      properties, nanoparticles are suitable for cellular-level diagnostics and
      therapy, offering numerous applications in medicine, e.g. development of
      biomedical devices, tissue repair, drug delivery systems and biosensors. In
      nanomedicine, recent studies are producing large amounts of structural and
      property data, highlighting the role for computational approaches in information
      management. While in vitro and in vivo assays are expensive, the cost of
      computing is falling. Furthermore, improvements in the accuracy of computational
      methods (e.g. data mining, knowledge discovery, modeling and simulation) have
      enabled effective tools to automate the extraction, management and storage of
      these vast data volumes. Since this information is widely distributed, one major
      issue is how to locate and access data where it resides (which also poses data
      sharing limitations). The novel discipline of nanoinformatics addresses the
      information challenges related to nanotechnology research. In this paper, we
      summarize the needs and challenges in the field and present an overview of extant
      initiatives and efforts.

PMID- 24932212
TI  - Development of forensic mental health services in Japan: working towards the
      reintegration of offenders with mental disorders.
AB  - BACKGROUND: Until the recent enactment of the Medical Treatment and Supervision
      Act (MTSA) in 2005, neither legislations nor facilities for mentally disordered
      offenders were available in Japan. The aim of the country's forensic mental
      health services, based on this new law, is to improve the social reintegration of
      mentally disordered offenders. In order to provide optimal psychiatric care to
      these individuals, specialised court proceedings, treatment facilities, and
      concrete guidelines have been established. The aim of this study was to review
      the current status of the new system and to clarify future challenges for
      improving services. METHODS: The authors collected official statistics regarding
      the new system published separately by the Ministry of Health, Labour and
      Welfare, the Ministry of Justice, and the Supreme Court of Japan. We aggregated
      the data and examined the system's current implementation status, nationwide.
      RESULTS: There were 2,750 requests for enrolment in the MTSA system between its
      initiation in 2005 and 31 December 2012. Of those requests, 2,724 cases had been
      concluded in court. In 63.1% of the cases, an inpatient treatment order had been
      made; 82.4% of those inpatients were diagnosed with schizophrenia. By the end of
      March 2012, two patients completing treatment under the MTSA had re-committed a
      serious offense. While overall designated inpatient and outpatient treatment
      facilities have reached national targets in terms of resources and beds
      available, a regional gap in MTSA designated facilities remains and the number of
      patients under inpatient treatment order is on the increase. CONCLUSIONS:
      Overall, the MTSA system has been running smoothly without encountering any
      serious problems. However, several concerns have emerged, such as the
      accumulation of patients under inpatient treatment order and insufficient
      regional resources. To more successfully promote the reintegration of mentally
      disordered offenders, improvements in outpatient treatment and welfare services
      are crucial. In order to install effective measures to help improve the system, a
      nationwide database of patients being treated under order of the MTSA should be
      properly built and maintained.

PMID- 24932213
TI  - Report on the international colloquium on cardio-oncology (rome, 12-14 march
      2014).
AB  - Cardio-oncology is a relatively new discipline that focuses on the cardiovascular
      sequelae of anti-tumour drugs. As any other young adolescent discipline, cardio
      oncology struggles to define its scientific boundaries and to identify best
      standards of care for cancer patients or survivors at risk of cardiovascular
      events. The International Colloquium on Cardio-Oncology was held in Rome, Italy,
      12-14 March 2014, with the aim of illuminating controversial issues and unmet
      needs in modern cardio-oncology. This colloquium embraced contributions from
      different kind of disciplines (oncology and cardiology but also paediatrics,
      geriatrics, genetics, and translational research); in fact, cardio-oncology goes
      way beyond the merging of cardiology with oncology. Moreover, the colloquium
      programme did not review cardiovascular toxicity from one drug or the other,
      rather it looked at patients as we see them in their fight against cancer and
      eventually returning to everyday life. This represents the melting pot in which
      anti-cancer therapies, genetic backgrounds, and risk factors conspire in
      producing cardiovascular sequelae, and this calls for screening programmes and
      well-designed platforms of collaboration between one key professional figure and
      another. The International Colloquium on Cardio-Oncology was promoted by the
      Menarini International Foundation and co-chaired by Giorgio Minotti (Rome),
      Joseph R Carver (Philadelphia, Pennsylvania, United States), and Steven E
      Lipshultz (Detroit, Michigan, United States). The programme was split into five
      sessions of broad investigational and clinical relevance (what is
      cardiotoxicity?, cardiotoxicity in children, adolescents, and young adults,
      cardiotoxicity in adults, cardiotoxicity in special populations, and the future
      of cardio-oncology). Here, the colloquium chairs and all the session chairs
      briefly summarised what was said at the colloquium. Topics and controversies were
      reported on behalf of all members of the working group of the International
      Colloquium on Cardio-Oncology. 

PMID- 24932214
TI  - Collaboration across continents to produce e-learning for palliative care
      education in Sub Saharan Africa.

PMID- 24932215
TI  - Twenty years of activity at the European Institute of Oncology, Milan, Italy.

PMID- 24932216
TI  - Chlorella for protein and biofuels: from strain selection to outdoor cultivation
      in a Green Wall Panel photobioreactor.
AB  - BACKGROUND: Chlorella is one of the few microalgae employed for human
      consumption. It typically has a high protein content, but it can also accumulate
      high amounts of lipids or carbohydrates under stress conditions and, for this
      reason, it is of interest in the production of biofuels. High production costs
      and energy consumption are associated with its cultivation. This work describes a
      strategy to reduce costs and environmental impact of Chlorella biomass production
      for food, biofuels and other applications. RESULTS: The growth of four Chlorella
      strains, selected after a laboratory screening, was investigated outdoors in a
      low-cost 0.25 m(2) GWP-II photobioreactor. The capacity of the selected strains
      to grow at high temperature was tested. On the basis of these results, in the
      nitrogen starvation trials the culture was cooled only when the temperature
      exceeded 40 degrees C to allow for significant energy savings, and performed in a
      seawater-based medium to reduce the freshwater footprint. Under nutrient
      sufficiency, strain CH2 was the most productive. In all the strains, nitrogen
      starvation strongly reduced productivity, depressed protein and induced
      accumulation of carbohydrate (about 50%) in strains F&M-M49 and IAM C-212, and
      lipid (40 - 45%) in strains PROD1 and CH2. Starved cultures achieved high storage
      product productivities: 0.12 g L(-1) d(-1) of lipids for CH2 and 0.19 g L(-1) d(
      1) of carbohydrates for F&M-M49. When extrapolated to large-scale in central
      Italy, CH2 showed a potential productivity of 41 t ha(-1) y(-1) for biomass, 16 t
      ha(-1) y(-1) for protein and 11 t ha(-1) y(-1) for lipid under nutrient
      sufficiency, and 8 t ha(-1) y(-1) for lipid under nitrogen starvation.
      CONCLUSIONS: The environmental and economic sustainability of Chlorella
      production was enhanced by growing the organisms in a seawater-based medium, so
      as not to compete with crops for freshwater, and at high temperatures, so as to
      reduce energy consumption for cooling. All the four selected strains are good
      candidates for food or biofuels production in lands unsuitable for conventional
      agriculture. Chlorella strain CH2 has the potential for more than 80 tonnes of
      biomass, 32 tonnes of protein and 22 tonnes of lipid per year under favourable
      climates.

PMID- 24932217
TI  - Understanding cost drivers and economic potential of two variants of ionic liquid
      pretreatment for cellulosic biofuel production.
AB  - BACKGROUND: Ionic liquid (IL) pretreatment could enable an economically viable
      route to produce biofuels by providing efficient means to extract sugars and
      lignin from lignocellulosic biomass. However, to realize this, novel IL-based
      processes need to be developed in order to minimize the overall production costs
      and accelerate commercial viability. In this study, two variants of IL-based
      processes are considered: one based on complete removal of the IL prior to
      hydrolysis using a water-wash (WW) step and the other based on a "one-pot" (OP)
      process that does not require IL removal prior to saccharification. Detailed
      techno-economic analysis (TEA) of these two routes was carried out to understand
      the cost drivers, economic potential (minimum ethanol selling price, MESP), and
      relative merits and challenges of each route. RESULTS: At high biomass loading
      (50%), both routes exhibited comparable economic performance with an MESP of
      $6.3/gal. With the possible advances identified (reduced water or acid/base
      consumption, improved conversion in pretreatment, and lignin valorization), the
      MESP could be reduced to around $3/gal ($3.2 in the WW route and $2.8 in the OP
      route). CONCLUSIONS: It was found that, to be competitive at industrial scale,
      lowered cost of ILs used and higher biomass loadings (50%) are essential for both
      routes, and in particular for the OP route. Overall, while the economic potential
      of both routes appears to be comparable at higher biomass loadings, the OP route
      showed the benefit of lower water consumption at the plant level, an important
      cost and sustainability consideration for biorefineries.

PMID- 24932219
TI  - Incidence of adverse events in an integrated US healthcare system: a
      retrospective observational study of 82,784 surgical hospitalizations.
AB  - BACKGROUND: Many health care facilities have developed electronic reporting
      systems for identifying and reporting adverse events (AEs), so that measures can
      be taken to improve patient safety. Although several studies have examined AEs in
      surgical settings, there has not previously been a systematic assessment of the
      variations in adverse event rates among different types of surgery, nor an
      identification of the particular types of AEs that are most common within each
      surgical category. Additionally, this study will identify the AE severity level
      associated with each of the AE category types. METHODS: This retrospective
      observational study was conducted at three Midwestern hospitals that are part of
      a large integrated healthcare system. Data from 2006 through 2009 were analyzed
      to determine the rates of reported adverse events (per 1,000 hospitalizations
      involving a surgical procedure) for 96 categories of surgery as classified
      according to the ICD-9-CM procedural coding system. Univariate and bivariate
      summary statistics were compiled for AEs by type, severity, and patient age.
      RESULTS: During the four-year study period, there was a total of 82,784 distinct
      hospitalizations involving at least one surgical procedure at these three
      hospitals. At least one adverse event was reported at 5,368 (6.5%) of those
      hospitalizations. The mean rate of AEs among all surgical procedure groups was
      82.8 AEs per 1,000 hospitalizations. Adverse event rates varied widely among
      surgical categories with a high of 556.7 AEs per 1,000 hospitalizations for
      operations on the heart and pericardium. The most common type of adverse event
      involved care management, followed by medication events and events related to
      invasive procedures. CONCLUSIONS: Detecting variations in AEs among surgical
      categories can be useful for surgeons and for hospital quality assurance
      personnel. Documenting the specific AE incidence rates among the most common
      types of surgical categories, and determining AE severity and age distributions
      within surgical categories will enable officials to better identify specific
      patient safety needs and develop appropriately targeted interventions for
      improvement.

PMID- 24932218
TI  - Butanol tolerance regulated by a two-component response regulator Slr1037 in
      photosynthetic Synechocystis sp. PCC 6803.
AB  - BACKGROUND: Butanol production directly from CO2 in photosynthetic cyanobacteria
      is restricted by the high toxicity of butanol to the hosts. In previous studies,
      we have found that a few two-component signal transduction systems (TCSTSs) were
      differentially regulated in Synechocystis sp. PCC 6803 after butanol treatment.
      RESULTS: To explore regulatory mechanisms of butanol tolerance, in this work, by
      constructing gene knockout mutants of the butanol-responsive TCSTS genes and
      conducting tolerance analysis, we uncovered that an orphan slr1037 gene encoding
      a novel response regulator was involved in butanol tolerance in Synechocystis.
      Interestingly, the ?slr1037 mutant grew similarly to the wild type under several
      other stress conditions tested, which suggests that its regulation on butanol
      tolerance is specific. Using a quantitative iTRAQ LC-MS/MS proteomics approach
      coupled with real-time reverse transcription PCR, we further determined the
      possible butanol-tolerance regulon regulated by Slr1037. The results showed that,
      after slr1037 deletion, proteins involved in photosynthesis and
      glycolysis/gluconeogenesis of central metabolic processes, and glutaredoxin,
      peptide methionine sulfoxide reductase and glucosylglycerol-phosphate synthase
      with stress-responsive functions were down-regulated, suggesting that Slr1037 may
      exhibit regulation to a wide range of cellular functions in combating butanol
      stress. CONCLUSIONS: The study provided a proteomic description of the putative
      butanol-tolerance regulon regulated by the slr1037 gene. As the first signal
      transduction protein identified directly related to butanol tolerance, response
      regulator Slr1037 could be a natural candidate for transcriptional engineering to
      improve butanol tolerance in Synechocystis.

PMID- 24932220
TI  - The expression of the Sprouty 1 protein inversely correlates with growth,
      proliferation, migration and invasion of ovarian cancer cells.
AB  - BACKGROUND: Our recent study on a panel of human ovarian cancer cells revealed
      that SKOV-3 cells barely express the Sprouty isoform 1 (Spry1) while 1A9 cells
      maintain it at a level similar to normal ovarian cells. Here we investigated the
      functional outcomes of induced alterations in the expression of Spry1 in the two
      cell lines in vitro. METHODS: Using the Spry1 specific plasmid and siRNA, the
      expression of Spry1 was induced and conversely silenced in SKOV-3 and 1A9 cells,
      respectively. The functional outcome was investigated by means of proliferation,
      MTT, scratch-wound, migration and invasion assays and selection of the stable
      clones. Mechanism of the effect was explored by Western blot. RESULTS: In the
      Spry1-transfected SKOV-3 cells, a significant reduction in growth and
      proliferation was evident. Stable clones of the Spry1-transfected SKOV-3 were
      almost undetectable after day 14. The number of migrated and invaded cells and
      the percentage of the scratch closure were significantly lower in the Spry1
      transfected group. Spry1 silencing in 1A9 cells, on the other hand, led to a
      significant increase in cell growth and proliferation. The number of migrated and
      invaded cells and the percentage of the scratch closure significantly increased
      in Spry1-silenced 1A9 group. Mechanistically, overexpression of Bax, activation
      of caspases 3, 7, 8 and 9, cleavage of PARP and attenuation of Bcl-2 and Bcl-xl
      were observed along with reduced activation of Erk and Akt and increased amount
      and activity of PTEN in the Spry1-transfected SKOV-3 cells. CONCLUSIONS: Here, we
      report the inverse correlation between the expression of Spry1 and growth,
      proliferation, invasion and migration of ovarian cancer cells.

PMID- 24932222
TI  - Current and future management of diabetic retinopathy: a personalized evidence
      based approach.
AB  - Diabetic retinopathy (DR) is the leading cause of new-onset blindness in working
      age individuals in the USA and represents a growing worldwide epidemic. Classic
      risk factors for onset or progression of DR include poor glycemic control,
      hypertension and hyperlipidemia; however, these factors account for only a small
      proportion of the risk of DR. New systemic risk factors are emerging, which may
      allow for personalized risk profiling and targeted treatment by physicians. In
      addition, early studies of vitreous fluid in patients with DR have resulted in a
      new paradigm: diabetes causes inflammation in the retina, which is mediated by
      multiple small signaling molecules that induce angiogenesis and vascular
      permeability. Future treatment of DR may involve two approaches: early vitreous
      analysis, followed by drug treatment targeted to the unique vitreous composition
      of the patient; and collaboration between ophthalmologists and primary care
      providers to address the unique systemic risk profile of each diabetic patient.

PMID- 24932221
TI  - The impact of Toll-like-receptor-9 on intestinal microbiota composition and extra
      intestinal sequelae in experimental Toxoplasma gondii induced ileitis.
AB  - BACKGROUND: Following peroral Toxoplasma (T.) gondii infection, susceptible mice
      develop acute ileitis due to a microbiota-dependent Th1 type immunopathology.
      Toll-like-receptor (TLR)-9 is known to recognize bacterial DNA and mediates
      intestinal inflammation, but its impact on intestinal microbiota composition and
      extra-intestinal sequelae following T. gondii infection has not yet been
      elucidated. METHODS AND RESULTS: Seven days following peroral infection (p.i.)
      with 100 cysts of T. gondii ME49 strain, TLR-9(-/-) and wildtype (WT) mice
      suffered from comparable ileitis, whereas ileal parasitic loads as well as IFN
      gamma and nitric oxide levels were higher in TLR-9(-/-) compared to WT mice.
      Locally, TLR-9(-/-) mice exhibited increased ileal CD3+, but not FOXP3+ cell
      numbers at day 7 p.i.; in mesenteric lymph nodes IFN-gamma-producing CD4+ cell
      numbers and TNF-alpha and IFN-gamma concentrations were also increased in TLR-9(
      /-) compared to WT mice. T. gondii DNA levels, however, did not differ in mice of
      either genotype. Differences in intestinal microbiota were rather subtle except
      for bifidobacteria that were virtually absent in both, naive and T. gondii
      infected TLR-9(-/-), but not WT mice. Extra-intestinally, TLR-9(-/-) mice
      displayed less distinct systemic immune responses as indicated by lower serum IL
      6, and splenic TNF-alpha and IFN-gamma levels as compared to WT mice despite
      higher translocation rates of intestinal bacteria to extra-intestinal
      compartments such as liver, spleen, kidney, and cardiac blood. Most importantly,
      brains were also affected in this inflammatory scenario as early as day 7 p.i.
      Remarkably, TLR-9(-/-) mice exhibited more pronounced inflammatory infiltrates
      with higher numbers of F4/80+ macrophages and microglia in the cortex and
      meninges as compared to WT mice, whereas T. gondii DNA levels did not differ.
      CONCLUSION: We here show that TLR-9 is not required for the development of T.
      gondii induced ileitis but mediates distinct inflammatory changes in intestinal
      and extra-intestinal compartments including the brain.

PMID- 24932223
TI  - Post-meal beta-cell function predicts the efficacy of glycemic control in
      patients with type 2 diabetes inadequately controlled by metformin monotherapy
      after addition of glibenclamide or acarbose.
AB  - BACKGROUND: This study aimed to explore parameters which will predict good
      control of HbA1c after adding a second anti-diabetic drug in patients with type 2
      diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy.
      METHODS: Fifty-one patients (M/F: 25/26, mean age: 53.7 +/- 8.2 years, mean
      glycated hemoglobin [HbA1c] 8.4 +/- 1.2%) with T2DM inadequately controlled with
      metformin were randomized to add-on glibenclamide or acarbose for 16 weeks.
      Before and after combination therapy, the subjects underwent a 2-hour liquid
      mixed meal tolerance test to determine insulin secretion (HOMA-beta,
      insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR
      and Matsuda insulin sensitivity index). RESULTS: At baseline, there was a
      significant inverse relationship between DI120 and HbA1c (p = 0.001) in all
      subjects. The addition of glibenclamide and acarbose improved HbA1c significantly
      from 8.6 +/- 1.6% to 7.4 +/- 1.2% (p < 0.001), and from 8.2 +/- 0.8% to 7.5 +/-
      0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly
      increased from 51.2 +/- 24.2 to 74.9 +/- 41.9 (p < 0.05), and in the acarbose
      group, from 62.5 +/- 31.4 to 91.7 +/- 36.2 (p < 0.05), respectively. Multiple
      regression analyses showed that both baseline HbA1c and DI120 independently
      predicted reduction of HbA1c as well as final HbA1c after combination therapy.
      CONCLUSIONS: In patients with T2DM inadequately controlled with metformin, add-on
      oral anti-diabetic agent with glibenclamide or acarbose resulted in the
      significant HbA1c reduction and improvement of beta-cell function. Subjects with
      greater baseline beta-cell function reserve displayed better glycemic response in
      the combination therapy of metformin with glibenclamide or acarbose. TRIAL
      REGISTRATION: This study was registered in the ClinicalTrials.gov with
      registration number of NCT00417729.

PMID- 24932224
TI  - Serum retinol-binding protein 4 levels are elevated but do not contribute to
      insulin resistance in newly diagnosed Chinese hypertensive patients.
AB  - BACKGROUND: Insulin resistance (IR) is closely correlated with cardiovascular
      disease (CVD). Retinol-binding protein 4 (RBP4) is a novel adipokine that
      modulates the action of insulin in various diseases. This study addressed the
      relationship between RBP4 and IR in newly diagnosed essential hypertension.
      METHODS: Serum RBP4, anthropometric and metabolic parameters were determined in
      267 newly diagnosed essential hypertensive patients not taking antihypertensive
      medications. The patients along with 64 control (NC) normotensive and lean
      subjects paired by age and sex were divided into two groups depending on body
      mass index (BMI), hypertension with obesity (HPO) and hypertension without
      obesity (HP). RESULTS: A striking difference was observed in RBP4 levels between
      the HP and NC groups. Significantly higher levels were noted in the HP group
      compared with the NC group; slightly, but not significantly, lower levels were
      observed in the HPO group compared with the HP group. After adjusting for BMI, WC
      and WHR, a modestly linear relationship was observed between RBP4 levels and SBP
      (r = 0.377; p = 0.00), DBP (r = 0.288; p = 0.00) and HOMA-beta(r = 0.121; p =
      0.028). Multiple stepwise regression analysis showed that SBP, WHR and drinking
      were independently related with serum RBP4 levels. CONCLUSIONS: The results of
      this study indicated that RBP4 levels were increased in naive hypertensive
      patients; however, no differences were observed in obese or non-obese
      hypertensive subjects. Our data suggest for the first time that RBP4 levels are
      significantly increased but do not contribute to the development of IR in newly
      diagnosed hypertensive Chinese patients.

PMID- 24932225
TI  - High adiposity: risk factor for dementia and Alzheimer's disease?
AB  - Higher levels of total and central adiposity, measured as higher body mass index
      (BMI) (in kilograms per square meter), waist circumference, or waist-to-hip
      ratio, have been associated with late-onset Alzheimer's disease (AD). However,
      some epidemiologic studies do not support this association, and potential
      underlying biological mechanisms that provide biological plausibility are not
      clear in terms of providing direct links to adipose tissue. Studies linking
      adiposity to AD have considered adiposity measures from mid-life and late-life.
      Given an evolving background trajectory of BMI that exists over the life course
      and the influence of dementia processes on BMI, results have been conflicting
      depending on when BMI is measured in relationship to clinical AD onset. This has
      made interpretation of the BMI-AD literature difficult. This debate will briefly
      review the epidemiologic evidence for and against an association between higher
      adiposity and AD, issues of timing of the adiposity measure in relation to AD
      onset, potential biological mechanisms for observed associations, and
      explanations for conflicting evidence. 

PMID- 24932226
TI  - Heterogeneity and Risk Sharing in Village Economies.
AB  - We show how to use panel data on household consumption to directly estimate
      households' risk preferences. Specifically, we measure heterogeneity in risk
      aversion among households in Thai villages using a full risk-sharing model, which
      we then test allowing for this heterogeneity. There is substantial, statistically
      significant heterogeneity in estimated risk preferences. Full insurance cannot be
      rejected. As the risk sharing, as-if-complete-markets theory might predict,
      estimated risk preferences are unrelated to wealth or other characteristics. The
      heterogeneity matters for policy: Although the average household would benefit
      from eliminating village-level risk, less-risk-averse households who are paid to
      absorb that risk would be worse off by several percent of household consumption.

PMID- 24932228
TI  - Repopulation of tumor cells during fractionated radiotherapy and detection
      methods (Review).
AB  - Repopulation of tumor cells during radiotherapy is believed to be a significant
      cause for treatment failure. The phenomenon of tumor repopulation during
      fractionated radiotherapy was found from clinical observations that identified
      that the local control rate decreased with a prolonged treatment time. A series
      of animal experiments with varied overall treatment time and fractionated doses
      were performed to demonstrate tumor cell repopulation during radiotherapy in
      various mouse xenograft models. However, conventional detection methods are
      challenging, as it is difficult to separate viable cells from those destined for
      apoptosis during fractionated radiotherapy. In essence, the mechanism of tumor
      repopulation involves the continuing proliferation of clonogenic tumor cells. In
      vivo imaging, tracking and targeting of the repopulation of these cells has been
      of clinical interest so as to administer a higher dose to the tumor repopulation
      regions. Currently, functional imaging methods, including 3'-deoxy-3'-18F
      fluorothymidine positron emission tomography (18F-FLT PET), are showing promise
      in assessing the proliferation activity of tumors in vivo. This review mainly
      focuses on the phenomenon of tumor repopulation during radiotherapy and its
      conventional and novel detection methods, particularly on the feasibility of 18F
      FLT PET for the detection of tumor-cell repopulation.

PMID- 24932229
TI  - 'Druggable' alterations detected by Ion Torrent in metastatic colorectal cancer
      patients.
AB  - The frequency and poor prognosis of patients with metastatic colorectal cancer
      (mCRC) emphasizes the requirement for improved biomarkers for use in the
      treatment and prognosis of mCRC. In the present study, somatic variants in exonic
      regions of key cancer genes were identified in mCRC patients. Formalin-fixed,
      paraffin-embedded tissues obtained by biopsy of the metastases of mCRC patients
      were collected, and the DNA was extracted and sequenced using the Ion Torrent
      Personal Genome Machine. For the targeted amplification of known cancer genes,
      the Ion AmpliSeqTM Cancer Panel, which is designed to detect 739 Catalogue of
      Somatic Mutations in Cancer (COSMIC) mutations in 604 loci from 46 oncogenes and
      tumor suppressor genes using as little as 10 ng of input DNA, was used. The
      sequencing results were then analyzed using the AmpliseqTM Variant Caller plug-in
      within the Ion Torrent Suite software. In addition, Ingenuity Pathway software
      was used to perform a pathway analysis. The Cox regression analysis was also
      conducted to investigate the potential correlation between alteration numbers and
      clinical factors, including response rate, disease-free survival and overall
      survival. Among 10 specimens, 65 genetic alterations were identified in 24 genes
      following the exclusion of germline mutations using the SNP database, whereby 41%
      of the alterations were also present in the COSMIC database. No clinical factors
      were found to significantly correlate with the alteration numbers in the patients
      by statistical analysis. However, pathway analysis identified 'colorectal cancer
      metastasis signaling' as the most commonly mutated canonical pathway. This
      analysis further revealed mutated genes in the Wnt, phosphoinositide 3-kinase
      (PI3K)/AKT and transforming growth factor (TGF)-beta/SMAD signaling pathways.
      Notably, 11 genes, including the expected APC, BRAF, KRAS, PIK3CA and TP53 genes,
      were mutated in at least two samples. Notably, 90% (9/10) of mCRC patients
      harbored at least one 'druggable' alteration (range, 1-6 alterations) that has
      been linked to a clinical treatment option or is currently being investigated in
      clinical trials of novel targeted therapies. These results indicated that DNA
      sequencing of key oncogenes and tumor suppressors enables the identification of
      'druggable' alterations for individual colorectal cancer patients.

PMID- 24932227
TI  - Inflammation to cancer: The molecular biology in the pancreas (Review).
AB  - Inflammatory responses are known to be correlated with cancer initiation and
      progression, and exploration of the route from inflammation to cancer makes a
      great contribution in elucidating the mechanisms underlying cancer development.
      Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and
      a poor prognosis. As chronic pancreatitis is considered to be a significant
      etiological factor for PC development, the current review aims to describe the
      molecular pathways from inflammation to pancreatic carcinogenesis, in support of
      the strategies for the prevention, diagnosis and treatment of PC.

PMID- 24932230
TI  - Anaplastic thyroid carcinoma with diffuse thoracic skin metastasis: A case
      report.
AB  - Anaplastic thyroid carcinoma is a significantly fatal endocrine neoplasm, with an
      average survival time of 4-12 months following diagnosis. The present study
      reports the case of a 57-year-old male patient who presented to the Bagcilar
      Training and Research Hospital (Istanbul, Turkey) due to swelling in the neck and
      difficulty swallowing. The jugular mass biopsy results were consistent with a
      diagnosis of anaplastic thyroid cancer. The patient was regarded to have advanced
      stage subcarinal, paratracheal, aortopulmonary, trancheobronchial and mediastinal
      lymphadenopathies and exhibited a good prognosis following chemotherapy. However,
      the patient succumbed one month later due to the emergence of diffuse skin
      lesions. The histopathological and immunohistochemical assessment of the skin
      biopsy displayed the characteristics of the underlying thyroid carcinoma.

PMID- 24932231
TI  - Analysis of continuous first-line treatment with docetaxel and carboplatin for
      advanced non-small cell lung cancer.
AB  - The present study aimed to analyze the efficacy and safety of multiple cycles of
      docetaxel and carboplatin (CBDCA) as a first-line treatment in patients with
      advanced non-small cell lung cancer (NSCLC). Patients with stage III or IV NSCLC,
      whose treatment began between July 1999 and February 2003, were retrospectively
      evaluated. Relatively low doses of docetaxel and CBDCA were administered for as
      many cycles as possible. The primary outcome assessed was the overall survival
      (OS) time, and the secondary outcomes included progression-free survival (PFS)
      time, response rate (RR) and adverse events. The median cycle number was four
      (range, 2-12). The median OS time was 400 days, and for adenocarcinoma and non
      adenocarcinoma, the OS time was 490 and 192 days, respectively. The median PFS
      time was 176 days and the RR was 66.7%. The main toxicity of the treatment was
      neutropenia, with grade 3 or 4 neutropenia occurring in 81.0% of patients.
      Continuous first-line treatment with this regimen may have encouraging effects
      within a certain group of advanced NSCLC patients, thereby warranting further
      investigations.

PMID- 24932233
TI  - Involvement of RbAp48 in erythroid differentiation of murine erythroleukemia
      cells induced by sodium butyrate.
AB  - Normal mammalian terminal erythroid differentiation is a precisely regulated
      process during which the progenitor cells execute particular programs to form a
      mature erythrocytic phenotype. In the present study, it was found that RbAp48, a
      histone-binding protein associated with retinoblastoma protein, was upregulated
      during terminal erythroid maturation in vivo and in vitro. This indicated that
      RbAp48, at least in part, participated in the regulation of murine
      erythropoiesis. Following sodium butyrate (SB) induction, murine erythroleukemia
      (MEL) cells began to re-enter erythroid differentiation and the ratio of
      differentiated cells reached ~80% at 72 h. The erythroid maturation-related mRNA
      expression of alpha-globin, beta-globin and glycophorin A (GPA) was increased
      markedly, which indicated that SB induced MEL differentiation. During MEL
      differentiation, the RbAp48 level showed a 1.5-fold increase at 72 h, and the
      globin transcription factor (GATA)-1 level was also upregulated in the early
      stage of differentiation. By contrast, the c-Myc level was gradually
      downregulated in MEL differentiation. Using an immunofluorescence assay, the
      results of the study directly showed that the average fluorescence intensity of
      RbAp48 in each cell reached an almost 1.7-fold increase at 72 and 96 h. This was
      consistent with the western blot results of RbAp48 during MEL differentiation. In
      addition, reduced expression of RbAp48 by RNA inference decreased SB-induced MEL
      differentiation by ~20%, indicating that a high level of RbAp48 was essential for
      MEL differentiation. Taken together, these results established a functional link
      between RbAp48 and erythroid differentiation.

PMID- 24932232
TI  - O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for
      basal-like breast cancer treated with cyclophosphamide-based chemotherapy.
AB  - The O6-methylguanine-DNA methyltransferase (MGMT) protein protects cells from
      alkylating agents by removing alkyl groups from the O6-position of guanine.
      However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear.
      The present study investigated whether MGMT expression was correlated with
      prognosis in patients with breast cancer that was managed according to a common
      therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic
      subtypes and MGMT protein expression levels were assessed in 635 consecutive
      patients with breast cancer using immunohistochemistry. In total, 425 (67%)
      luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor
      2+/estrogen receptor- (HER2+/ER-) and 48 (8%) basal-like subtypes were
      identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast
      cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER- and 46% of basal
      like subtypes were positive. The overall survival (OS) and disease-free survival
      (DFS) rates did not significantly differ according to the MGMT status among
      patients with luminal A, luminal B or HER2+/ER- subtypes, and patients with MGMT
      negative basal-like cancers tended to have a longer DFS, but not a significantly
      longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and
      31% of patients with luminal A, luminal B, HER2+/ER- and basal-like tumors,
      respectively. Although the MGMT status and clinical outcomes of patients with the
      luminal A, luminal B or HER2+/ER- subtypes treated with CPM were not
      significantly correlated, the patients with MGMT-negative basal-like tumors who
      received CPM exhibited significantly improved DFS and OS compared with the CPM
      treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and
      predictive marker for CPM-containing chemotherapy in basal-like breast cancer.

PMID- 24932234
TI  - Glomus tumor in the stomach: A case report and review of the literature.
AB  - This study reports a rare case of a 47-year-old female with a gastric glomus
      tumor who was admitted with epigastralgia. Endoscopic ultrasound revealed a
      protrusion on the posterior wall of the gastric antrum. Enhanced computed
      tomography confirmed the presence of a 10-mm mass. The tumor was resected, and
      immunohistochemistry revealed the tumor to be positive for smooth muscle actin
      and collagen type IV, and negative for synaptophysin, chromogranin A, laminin, S
      100, cluster of differentiation (CD)34, CD31, CD99, cytokeratin (AE1/AE3), desmin
      and epithelial membrane antigen. The proliferation marker Ki-67 was positive in
      <5% of tumor cell nuclei. The clinical procedures with a review of the literature
      are reported.

PMID- 24932235
TI  - Metastatic testicular tumor presenting as a scrotal hydrocele: An initial
      manifestation of pancreatic adenocarcinoma.
AB  - Metastatic pancreatic adenocarcinoma involving the testis is a rare condition
      with a poor prognosis. The current study describes the case of a 69-year-old male
      who presented with a painful swelling of the left scrotum. Scrotal
      ultrasonography revealed hydroceles in the scrotal sacs, with the left one being
      larger in size. The patient underwent left hydrocelectomy and was eventually
      diagnosed with metastatic adenocarcinoma. Abdominal computed tomography, which
      was performed to detect the primary cancer, showed a pancreatic tail carcinoma
      with liver and multiple lymph node metastases, and peritoneal carcinomatosis. The
      patient received gemcitabine-based chemotherapy but resulted in progressive
      disease. This case shows that in a patient in whom a primary testicular tumor is
      unusual due to their age, a testicular mass or hydrocele should be a suspect for
      possible metastatic disease.

PMID- 24932236
TI  - Thyroid-like follicular carcinoma of the kidney: A report of two cases and
      literature review.
AB  - There have only been a few reports of thyroid-like follicular carcinoma of the
      kidney (TLFCK) to date. In the present study, two patients with TLFCK are
      reported. Patient 1 was a 65-year-old male exhibiting repeated hematuria and
      right back pain. No tumors were located in the patient's thyroid or lungs. The
      physical examination revealed percussion tenderness over the right kidney region
      was noticed. Enhanced computed tomography (CT) indicated a right renal pelvic
      carcinoma, for which the patient underwent a radical right nephrectomy. Patient 2
      was a 59-year-old male with a mass in the right kidney, located during a health
      examination and who exhibited no obvious clinical symptoms. The patient was
      clinically diagnosed with right renal carcinoma, confirmed by an enhanced CT. The
      patient underwent a radical right nephrectomy. The clinical features, imaging
      results, pathology, immune phenotypes, treatment and prognosis were analyzed. The
      associated literature was also reviewed. The cut surface of each tumor showed
      gray-white material with a central solid area, including scattered gray-brown
      necrotic and gray hemorrhagic areas and small cystic cavities. Microscopically,
      the arrangement of the tumor cells mimicked thyroid follicles with red-stained
      colloid-like material in the lumen. No renal hilar lymph node involvement was
      noted. The tumor tissue of patient 1 was immunohistochemically positive for
      vimentin, epithelial membrane antigen (EMA), cytokeratin (CK), CK7, and neuron
      specific enolase; and negative for CK34BE12, synapsin (Syn), CK20, cluster of
      differentiation 56 (CD56), CD10, Wilm's tumor-1 (WT-1), CD34, CD57, P53, CD99,
      thyroid transcription factor-1 (TTF-1), CD15 and thyroglobulin (TG); with a Ki-67
      labeling index (LI) of 30%. The tumor tissue of patient 2 was
      immunohistochemically positive for vimentin, EMA, CK7 and CK20; and negative for
      CD56, CD10, WT-1, CD34, CD57, P53, CD117, TTF-1, CD15, CD99, TG, chromogranin A
      and Syn; with a Ki-67 LI of 20%. TLFCK is a rare renal tumor with low malignancy
      but medium invasiveness. It morphologically resembles thyroid follicular
      carcinoma but does not express TTF-1 or TG. Radical nephrectomy can achieve good
      patient outcomes.

PMID- 24932237
TI  - SLC23A2-05 (rs4987219) and KRAS-LCS6 (rs61764370) polymorphisms in patients with
      squamous cell carcinoma of the head and neck.
AB  - Cancer is a genetic disease that is highly influenced by environmental factors.
      To determine the risk factors of squamous cell carcinoma of the head and neck,
      two polymorphisms, solute carrier family 23 member 2 (SLC23A2-05 [rs4987219]) and
      v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-LCS6 (rs61764370),
      and environmental factors, including smoking and alcohol consumption, were
      studied in a population. The present study included 165 males diagnosed with
      squamous cell carcinoma of the head and neck. The control group consisted of 230
      healthy male subjects without cancer or a family history of cancer. The SLC23A2
      05 and KRAS-LCS6 polymorphisms were analyzed by polymerase chain reaction
      followed by enzymatic digestion. All patients and healthy subjects were assessed
      with regard to their smoking habit and alcohol consumption as these are
      considered to be risk factors for cancer. The statistical analysis was performed
      using logistic regression, Fisher's exact and chi2 tests. Additional analyses
      were performed using the programs, multi-factor dimensionality reduction (MDR;
      version 2.0) and MDR permutation test (version 0.4.7), which consider all
      variables as risk factors simultaneously. The results of the present study
      demonstrate that the SLC23A2-05 and KRAS-LCS6 polymorphisms are not a risk factor
      for squamous cell carcinoma of the head and neck. In the same samples, the
      association of alcohol consumption (P<0.001) and smoking habit (P<0.001) with
      cancer presence was positive when each variable was considered individually.
      Concerning the environmental factors, a positive association of smoking habit and
      alcohol consumption with cancer, although not with ethnicity (ratio, 1.0244;
      testing balance accuracy, 0.8733; P<0.001) was identified using the MDR tool,
      which analyzed the variables and polymorphism genotypes simultaneously. In
      conclusion, in the present study, squamous cell carcinoma of the head and neck
      was highly affected by environmental factors when compared with the affect of
      SLC23A2-05 and KRAS-LCS6 polymorphisms.

PMID- 24932238
TI  - beta,beta-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing
      radiation through the upregulation of reactive oxygen species.
AB  - Shikonin, a naphthoquinone derivative, has been shown to possess antitumor
      activity. In the present study, the effects of shikonin and its analog, beta,beta
      dimethylacrylshikonin, were investigated as radiosensitizers on the human colon
      cancer cell line, HCT-116. Shikonin and, to a greater extent, its analog-induced
      apoptosis of HCT-116 cells further synergistically potentiated the induction of
      apoptosis when combined with ionizing radiation (IR) treatment. Shikonins also
      stimulated an increase in reactive oxygen species (ROS) production and IR-induced
      DNA damage. Pre-treatment with the ROS scavenger, N-acetylcysteine, suppressed
      the enhancement of IR-induced DNA damage and apoptosis stimulated by shikonins,
      indicating that shikonins exert their radiosensitizing effects through ROS
      upregulation. The radiosensitizing effect of shikonins was also examined in vivo
      using the xenograft mouse model. Consistent with the in vitro results, injection
      of beta,beta-dimethylacrylshikonin combined with IR treatment significantly
      suppressed tumor growth of the HCT-116 xenograft. Taken together, the results
      show that beta,beta-dimethylacrylshikonin is a promising agent for developing an
      improved strategy for radiotherapy against tumors.

PMID- 24932239
TI  - Modulation of microRNA expression in human lung cancer cells by the G9a histone
      methyltransferase inhibitor BIX01294.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of
      their target genes at the post-transcriptional level. In cancer cells, miRNAs,
      depending on the biological functions of their target genes, may have a tumor
      promoting or -suppressing effect. Treatment of cancer cells with inhibitors of
      DNA methylation and/or histone deacetylation modulates the expression level of
      miRNAs, which provides evidence for epigenetic regulation of miRNA expression.
      The consequences of inhibition of histone methyltransferase on miRNA expression,
      however, have not been thoroughly investigated. The present study examined the
      expression pattern of miRNAs in the non-small cell lung cancer cell line, H1299
      with or without treatment of BIX01294, a potent chemical inhibitor of G9a
      methyltransferase that catalyzes the mono-and di-methylation of the lysine 9
      residue of histone H3. By coupling microarray analysis with quantitative real
      time polymerase chain reaction analysis, two miRNAs were identified that showed
      consistent downregulation following BIX01294 treatment. The results indicate that
      histone H3 methylation regulates miRNA expression in lung cancer cells, which may
      provide additional insight for future chemical treatment of lung cancer.

PMID- 24932240
TI  - Usefulness of PET/CT for diagnosis of periosteal chondrosarcoma of the femur: A
      case report.
AB  - Periosteal chondrosarcoma is an extremely rare low-grade malignant cartilaginous
      tumor arising from the external bone surface. Diagnosis of periosteal
      chondrosarcomas may be challenging, since this condition closely resembles
      periosteal chondromas. It has been reported that positron emission tomography
      (PET) is useful in distinguishing benign from malignant cartilaginous tumors
      using a maximum standardized uptake value (SUVmax) cut-off of 2.0 or 2.3. This
      report presents the case of a 40-year-old female with an 18-month history of a
      tender mass in the left distal femur. Radiological findings demonstrated
      periosteal buttressing. Magnetic resonance imaging (MRI) revealed a chondrogenic
      tumor of 3 cm in size developing from the external bone surface. It was difficult
      to differentiate periosteal chondrosarcoma from periosteal chondroma on the basis
      of size and the radiological and MRI findings. PET/computed tomography (CT)
      revealed abnormal linear uptake with an SUVmax of 2.7, indicating a malignant
      tumor. A diagnosis of periosteal chondrosarcoma was made, and wide resection was
      performed. Tumor histology was consistent with grade II chondrosarcoma. PET/CT is
      thus useful in differentiating periosteal chondrosarcoma from periosteal
      chondroma.

PMID- 24932241
TI  - Non-surgical treatment of canine oral malignant melanoma: A case study of the
      application of complementary alternative medicine.
AB  - This report describes a dog with a clinical stage III oral malignant melanoma
      that was treated with complementary alternative medicine (CAM). The CAM included
      high temperature hyperthermia, dendritic cell therapy and lupeol injections.
      Surgery, radiation and chemotherapy were not performed. Two months after the
      start of treatment, the tumor disappeared and after six months, the follow-up
      examinations revealed no recurrence or metastasis of the tumor. Quality of life
      (QOL) of the dog was maintained; therefore, the application of CAM may be an
      effective treatment for canine oral malignant melanoma. The effective application
      of CAM has the potential to prolong life and maintain an excellent QOL for pets.

PMID- 24932242
TI  - Ethanol injection therapy for small hepatocellular carcinomas located beneath a
      large vessel using a curved percutaneous ethanol injection therapy needle.
AB  - Percutaneous ethanol injection therapy (PEIT) has been administered as a safe
      therapeutic modality for patients with small hepatocellular carcinoma (HCC). Due
      to the nature of the straight approaching line of a PEIT or radiofrequency
      ablation needle, penetrating the vessels that are interposed between the dermal
      insertion point and the nodule is unavoidable. A device with an overcoat needle
      and coaxial curved PEIT needle was created that facilitated a detour around
      interposing large vessels in order to avoid unnecessary harmful effects that
      result from the PEIT procedure. Two cases of HCC located adjacent to a
      neighboring large vessel were treated with a curved PEIT needle. The curved PEIT
      needle, which is connected to an outer needle, enabled deviation around the
      interposing vessels and successful connection with the HCC. Careful use of the
      curved line of the PEIT needle enabled the safe and successful performance of the
      PEIT without any requirement for specific training. This hand-assisted technique
      may be an applicable treatment for small HCC located beneath large vessels as a
      direct therapeutic method using ultrasound guidance.

PMID- 24932243
TI  - Primary central nervous system lymphoma with preceding spontaneous pseudotumoral
      demyelination in an immunocompetent adult patient: A case report and literature
      review.
AB  - The rapid disappearance of primary central nervous system lymphomas (PCNSL)
      following steroid therapy is common; however, the spontaneous regression of PCNSL
      without any treatment is extremely rare. This study presented a rare case of
      PCNSL with preceding pseudotumoral demyelination and no previous steroid
      treatment, and the pitfalls of PCNSL diagnosis were discussed. A 70-year-old
      healthy male experienced memory and gait disturbances and showed multiple
      enhanced lesions with perifocal brain edema in the left cerebrum. The patient had
      no previous symptoms, no chronic lesions and negative oligoclonal immunoglobulin
      G bands in the cerebrospinal fluid. Histological examination of a brain biopsy
      specimen revealed predominantly destructive, demyelinating characteristics with
      infiltration of several T lymphocytes and foamy macrophages resulting in the
      diagnosis of multiple sclerosis. The patient received steroid therapy and
      demonstrated gradual improvement, multiple brain lesions had disappeared from the
      magnetic resonance imaging (MRI)scan two months after the biopsy. However, three
      months after the biopsy, the condition of the patient deteriorated. MRI indicated
      a homogeneous enhanced lesion in the right frontal lobe and a second biopsy was
      performed. Histological examination during the second biopsy revealed a diffuse
      large B-cell lymphoma. The patient received whole-brain radiation and steroid
      therapy, however, succumbed eight months following the initial diagnosis. In the
      current report a comparison between the our case and six previously reported
      cases is presented.

PMID- 24932244
TI  - Adenoma of the nipple: A clinicopathological report of 13 cases.
AB  - Adenoma of the nipple (AN) represents a rare benign mammary proliferation of
      lactiferous ducts. It appears as an erosive or ulcerative lesion, which in a
      number of cases is associated with a serous/hematic secretion. AN may be
      clinically confused with Paget's disease and histologically with invasive breast
      carcinoma or breast cancer precursor lesions. Therefore, the histological and
      immunophenotypic analysis is essential for the differential diagnosis. The
      present study describes the histopathological characteristics of a first case
      series of AN.

PMID- 24932245
TI  - Lymphomatoid granulomatosis involving the central nervous system: A case report
      and review of the literature.
AB  - Lymphomatoid granulomatosis (LYG) is a rare tumor with unknown etiology. Specific
      etiological factors for LYG are also unknown, although previous data indicates
      that LYG is an Epstein-Barr virus-associated B-cell proliferation associated with
      an exuberant T-cell reaction. According to the 2008 WHO classification, LYG is
      characterized by B-cell proliferation of B-lymphoma cells. Generally, treatment
      options for LYG are similar to those for diffuse large B-cell lymphoma.
      Unfortunately, LYG is a chemotherapy-resistant disease in certain patients and
      has a poor prognosis. The current study presents the case of a 19-year-old male
      patient with pulmonary LYG. The patient exhibited progressive disease following
      one cycle of chemotherapy with cyclophosphamide, adriamycin, vincristine and
      prednisone, and nodular lesions in the brain were diagnosed. Radiotherapy was
      delivered to the whole brain, however, this treatment did not prevent progression
      of the disease and the patient succumbed three months after initial presentation.
      An overview of the literature with regard to the etiology, clinical features,
      diagnosis and treatment options for LYG is also presented in the current case
      study.

PMID- 24932246
TI  - DNA copy number alterations in pleomorphic leiomyosarcoma: A case report.
AB  - Pleomorphic leiomyosarcoma (P-LMS) is a rare morphological variant of LMS. The
      current study presents the cytogenetic data of a P-LMS that arose in the axillary
      region of a 31-year-old male. The results of array-based comparative genomic
      hybridization for the primary tumor showed DNA copy number alteration (DCNA)
      gains of 8ptel, 17ptel and 17q11.2 and losses of 2ptel, 7ptel, 7qtel, 10p15,
      12p12-13.1, 13q14.2-14.3, 15q25-26 and Yq11. However, a metastatic lesion showed
      cytogenetic data different from the primary tumor DCNAs, with only the locus of
      17ptel (282M15/SP6) in common between them. These observations add to the
      spectrum of DCNAs that have been reported in previous cases of LMS and provide
      novel cytogenetic data.

PMID- 24932247
TI  - Screening and functional analysis of a differential protein profile of human
      breast cancer.
AB  - To improve the understanding of the enriched functions of proteins and to
      identify potential biomarkers in human breast cancer, the present study
      constructed a differentially expressed protein profile by screening
      immunohistochemistry maps of human breast cancer proteins. A total of 1,688
      proteins were found to be differentially expressed in human breast cancer,
      including 773 upregulated and 915 downregulated proteins. Of these proteins,
      secreted and membrane proteins were screened and clustered, and more enriched
      biological functions and pathways were presented in the upregulated protein
      profiles. Furthermore, altered serum levels of peroxiredoxin (PRDX)2, PRDX6,
      cathepsin (CTS)B and CTSD were detected by ELISA assay. The present study
      provides a novel global mapping of potential breast cancer biomarkers that could
      be used as background to identify the altered pathways in human breast cancer, as
      well as potential cancer targets.

PMID- 24932248
TI  - Autologous bone marrow stem cell transplantation for the treatment of
      postoperative hand infection with a skin defect in diabetes mellitus: A case
      report.
AB  - Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for
      transplantation by virtue of limited rejection reactions and marked proliferative
      ability. This study presents a novel method by which MSCs were harvested from the
      bone marrow of a patient who presented with severe post-traumatic infection and a
      non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus
      (DM). An autologous MSC suspension was injected into the persistent skin defect
      after stabilizing the blood glucose level and appropriate infection control.
      During the course of a regular 18-month postoperative follow-up, the patient
      exhibited immediate recovery with no transplant-associated complications, as well
      as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may
      play a role in the clinical application of stem cells, particularly for treatment
      of skin defects following surgery in cases of DM and for those caused by various
      other traumas.

PMID- 24932249
TI  - E-cadherin and beta-catenin adhesion proteins correlate positively with connexins
      in colorectal cancer.
AB  - The majority of solid cancers present with qualitative and quantitative
      aberrations of adhesion proteins, including E-cadherin and beta-catenin, and
      connexin (Cx) gap junction proteins, which is consistent with alterations in the
      expression and location of such proteins in neoplastic cells. Since there are no
      data on the correlation between adhesion proteins and Cxs in human colorectal
      cancer (CRC), the aim of the present study was to evaluate the expression and
      correlation between these proteins. Tissue specimens were obtained from 151 cases
      of surgically removed colorectal adenocarcinomas. The samples were examined by
      immunohistochemistry with the use of antibodies against E-cadherin, beta-catenin
      and the three Cxs: Cx26, Cx32 and Cx43. The aberrant expression of the studied
      adhesion proteins (primarily cytoplasmic for E-cadherin and cytoplasmic and/or
      nuclear for beta-catenin) was observed, whereas only a minority of cases revealed
      normal membranous distribution of the labeling. The present study is the first in
      the literature to reveal a correlation between the expression of E-cadherin and
      beta-catenin and the examined Cxs in CRC in humans. The positive correlation
      between the Cxs, particularly Cx26 and Cx32, and the adhesive proteins occurred
      in patients without lymph node metastases and in the moderately differentiated
      tumors (G2). Such a dependency was not observed in the analysis of the
      correlation between Cx43 and E-cadherin. However, a positive correlation between
      these proteins was observed in patients with lymph nodes metastases.
      Additionally, a link between the expression of these adhesion proteins was
      observed. The present study indicates, for the first time, that the expression of
      adhesion proteins, E-cadherin and beta-catenin, is closely associated with the
      expression of three studied Cxs in CRC, and that this correlation may improve an
      understanding of the carcinogenic process in this cancer.

PMID- 24932250
TI  - High-level C-X-C chemokine receptor type 4 expression correlates with brain
      specific metastasis following complete resection of non-small cell lung cancer.
AB  - Brain-specific metastasis is one of the primary causes of recurrence following
      complete resection of non-small cell lung cancer (NSCLC) and the underlying
      mechanism remains unclear. The present study was designed to investigate the
      correlation between C-X-C chemokine receptor type 4 (CXCR4) expression and brain
      specific metastasis of NSCLC. Lung cancer tissues from 105 patients who underwent
      complete tumor resection between January 1998 and June 2008 (sample group, 34
      with brain metastasis during the follow-up period; control group 1, 34 without
      metastasis during the follow-up period; and control group 2, 37 with other organ
      metastasis, excluding brain metastasis, during the follow-up period) were
      examined by immunohistochemistry to detect the expression of CXCR4 protein. The
      differences in CXCR4 expression were compared using McNemar's chi2 test.
      Estimation of survival was calculated with the Kaplan-Meier method and the
      statistical differences were analyzed with the log-rank test. Overexpression of
      CXCR4 protein was observed in 31 (91.2%) NSCLC patients with brain metastasis,
      which was greater than that observed in the NSCLC patients with other organ
      metastases (73.0%; P=0.048) and without metastases (14.7%; P<0.001). CXCR4
      protein was highly overexpressed in patients with brain-specific metastasis,
      which indicated that high-level CXCR4 expression correlates with brain-specific
      metastasis of NSCLC.

PMID- 24932251
TI  - CyberKnife radiotherapy for malignant fibrous histiocytoma of the chest wall: A
      case report and review of the literature.
AB  - Malignant fibrous histiocytoma (MFH) is the most common type of soft tissue
      sarcoma, but rarely originates in the chest wall. Surgical resection is
      considered to be the most reliable treatment, however, no consensus has been
      reached concerning the best treatment for unresectable MFH. The current study
      presents the case of a 77-year-old male with MFH of the chest wall. The patient
      developed a painless mass and intermittent fever over a four-month period. A
      computed tomography scan demonstrated a large inhomogeneous lesion in the right
      chest wall, which was subsequently diagnosed via biopsy as a MFH. Since the tumor
      was an unresectable mass, CyberKnife(r) radiotherapy was conducted. Following the
      treatment, a marked reduction in the tumor size was observed with a tolerable
      level of toxicity. The sequencing analysis also revealed an in-frame deletion
      (delE746-A750) in exon 19 of the epidermal growth factor receptor gene. Based on
      this result, gefitinib was administered to the patient at a dose of 250 mg/day.

PMID- 24932252
TI  - Primary testicular lymphoma with subcutaneous masses as the sole manifestation of
      the first relapse and central nervous system lymphoma as the second relapse: A
      case report and literature review.
AB  - Primary testicular lymphoma (PTL) accounts for ~1% of all non-Hodgkin's lymphomas
      and has a marked tendency for systemic relapse. The current study presents a
      unique case of testicular diffuse large B-cell lymphoma of non-germinal center B
      cell subtype, with subcutaneous masses as the sole manifestation of the first
      relapse and central nervous system lymphoma as the second relapse. Subcutaneous
      relapse and subsequent brain relapse are extremely rare signs of PTL
      dissemination. The patient received methotrexate-based combined chemotherapy and
      achieved a partial response. This case presents a rare pattern of treatment
      failure in this malignant clinical entity.

PMID- 24932253
TI  - Pulmonary hamartoma resembling multiple metastases: A case report.
AB  - The current study presents the case of a patient with multiple pulmonary nodules
      as observed by computed tomography. Furthermore, a marginal increase in
      fluorodeoxyglucose uptake was identified by positron emission tomography. Due to
      the appearance of multiple small nodules and a history of radical nephrectomy, a
      hypothetical diagnosis of pulmonary metastasis of a previously excised renal
      carcinoma was determined, which was confirmed by biopsy. Video-assisted
      thoracoscopic surgical resection of the nodules was proposed and pathological
      examination exhibited an unforeseen and rare observation.

PMID- 24932254
TI  - High expression of octamer transcription factor 1 in cervical cancer.
AB  - Cervical carcinoma is the second most prevalent malignancy in females worldwide.
      The crucial etiologic factors involved in the development of cervical carcinoma
      include infection with papillomavirus, and the structural or functional mutation
      of oncogenes and tumor suppressor genes. The abnormal change of octamer
      transcription factor 1 (OCT1) is associated with tumor progression and a poor
      patient survival rate. However, little is known regarding the effect of OCT1 in
      cervical cancer. In the present study, flow cytometry, western blot analysis and
      quantitative polymerase chain reaction (qPCR) were peformed to identify
      differentially expressed OCT1 in cervical cancer tissue and adjacent non
      cancerous tissues. The normalized OCT1 gene expression in cervical cancer was
      5.98 times higher compared with the adjacent non-cancerous tissues. Western blot
      analysis and flow cytometry assessed the levels of OCT1 protein. The results of
      these two differential techniques showed that the protein expression level of
      OCT1 was greater in cervical cancer tissues, which corresponded with the qPCR
      results. Finally, as OCT1 is a potential target gene for microRNA (miR)-1467, 
      1185, -4493 and -3919, their expression levels were analyzed in cervical cancer
      tissues and adjacent non-cancerous tissues; they were downregulated by ~45% in
      the cervical cancer samples. The results of the present study showed that OCT1 is
      highly expressed in cervical cancer tissues and indicated that OCT-1 may be
      significant in cervical cancer.

PMID- 24932255
TI  - Isocitrate dehydrogenase mutation is associated with tumor location and magnetic
      resonance imaging characteristics in astrocytic neoplasms.
AB  - The molecular subsets of glioma behave in biologically distinct ways. The present
      study detected isocitrate dehydrogenase (IDH) 1 and IDH2 mutations in glioma to
      analyze whether IDH-mutated gliomas are situated in certain preferential areas
      and to investigate their correlation with magnetic resonance imaging (MRI)
      characteristics. A series of 193 patients with astrocytic neoplasms (111 diffuse
      and 82 anaplastic astrocytomas), grouped according to prelabeled anatomical
      structures and the risk of surgery, were retrospectively reviewed for IDH1 and
      IDH2 mutations to compare the tumor location and MRI features. A total of 111
      IDH1 mutations at codon 132 (57.5%) and six IDH2 mutations at codon 172 (3.1%)
      were detected. The IDH1/2 mutations were found to predict longer survival,
      independent of the histological type in this series of patients. The IDH-mutated
      gliomas were predominantly located in a single lobe, such as the frontal lobe,
      temporal lobe or cerebellum and rarely in the diencephalon or brain stem.
      Furthermore, according to the risk of surgery, the IDH-mutated tumors were rarely
      located in the high-risk regions of the brain, where surgery exhibits a high
      mortality rate intraoperatively and postoperatively. In addition, gliomas with
      IDH mutations were significantly more likely to exhibit a unilateral pattern of
      growth, sharp tumor margins, homogeneous signal intensity and less contrast
      enhancement on MRI. The results of the current study suggested that the prolonged
      survival of patients with IDH-mutated gliomas is primarily due to a less
      aggressive biological behavior according to tumor site and MRI features.

PMID- 24932257
TI  - Chronic lymphocytic leukemia presenting with ascites diagnosed by clonality
      analysis via gene rearrangement assay: A case report.
AB  - The diagnosis of chronic lymphocytic leukemia (CLL) presenting with ascites is
      predominantly based on the morphological and immunophenotypic characteristics,
      which are comparable to peripheral blood and bone marrow cells. However, it is
      relatively difficult to diagnose CLL due to the pleomorphism of the lymphocytes
      in ascites. The current study presents an 80-year-old male with a prior diagnosis
      of CLL who developed large ascites. Predominant T lymphocytes rendered
      morphological and immunophenotypic diagnosis difficult. Clonality analysis of
      immunoglobulin (Ig) gene rearrangements was performed on the lymphocytes from the
      ascites to diagnose the involvement of CLL, a laparotomy and biopsy from the
      peritoneal node confirmed the involvement of small lymphocytic lymphoma/CLL. The
      clonality analysis of Ig gene rearrangements may provide a powerful and accurate
      method for diagnosing CLL presenting with ascites.

PMID- 24932256
TI  - Synergistic killing of lung cancer cells by cisplatin and radiation via autophagy
      and apoptosis.
AB  - Cisplatin is a commonly used drug for chemotherapy, however, whether it may be
      used synergistically with radiotherapy remains unclear. The present study
      investigated the underlying mechanisms of synergistic killing by
      radiosensitization and cisplatin, with a focus on the growth inhibition,
      apoptosis and autophagy of non-small cell human lung cancer cells in vitro and in
      a tumor xenograft in vivo. A549 cells were used for the in vitro experiments and
      divided into the following four treatment groups: Sham-irradiated; conventional
      radiotherapy (CRT) of five doses of 2 Gy every day; hyperfractionated
      radiotherapy of five doses of 2 Gy (1 Gy twice a day at 4 h intervals) every day;
      and CRT plus cisplatin. A xenograft tumor-bearing C57BL/6 model was established
      for the in vivo experiments and the above-mentioned treatments were administered.
      MTT and colony formation assays were used to detect cell viability and western
      blotting was performed to detect the levels of protein expression.
      Monodansylcadaverine staining and the immunofluorescence technique were used to
      analyze the autophagy rate, while flow cytometry and immunohistochemistry were
      performed to detect the expression levels of the genes associated with apoptosis
      and autophagy, including microtubule-associated protein 1 light chain 3 (MAPLC3)
      II, phosphoinositide 3-kinase (PI3K) III, Beclin1, phosphorylated protein kinase
      B (p-AKT), damage-regulated autophagy modulator (DRAM), B-cell lymphoma 2 (Bcl
      2), Bcl-2-associated X protein, caspase-3 and p21. The MTT assay demonstrated
      that cisplatin exhibits a dose-dependent cytotoxicity in A549 cells and
      synergizes with radiation to promote the cell-killing effect of radiation. In the
      xenograft mouse model of Lewis cells, cisplatin plus ionizing radiation (IR)
      (five doses of 2 Gy) yielded the most significant tumor suppression. The
      autophagic vacuoles, the ratio of MAPLC3-II to MAPLC3-I (LC3-II/LC3-I) and the
      levels of Beclin1 were found to increase in all treatment groups, with the most
      marked upregulation observed in the CRT plus cisplatin treatment group. In
      addition, caspase-3 processing was enhanced in the group treated with the
      combination of cisplatin with radiation, compared with the group treated with
      radiation alone. Fractionated IR resulted in a significant increase in p21
      expression, which was further enhanced when combined with cisplatin. Furthermore,
      treatment with cisplatin and fractionated IR resulted in a significant elevation
      of the expression of the autophagy-related genes, PI3KIII, Beclin1 and DRAM1.
      However, the levels of p-AKT were observed to decline following exposure to
      fractionated IR in the presence or absence of cisplatin. As for the apoptosis
      signaling genes, the combination of cisplatin and fractionated IR therapy
      resulted in a significant decrease in Bcl-2 expression and a marked upregulation
      of p21 expression. The current study offers strong evidence that the combination
      of cisplatin with radiation strengthens the killing effect of radiation via pro
      apoptotic and pro-autophagic cell death.

PMID- 24932258
TI  - Primary carcinoma of the frontal sinus with extensive intracranial invasion: A
      case report and review of the literature.
AB  - Primary carcinoma of the frontal sinus is quite rare, with an incidence of 0.3
      1.0% of all paranasal sinus carcinomas. The early diagnosis is often difficult
      and the condition is often mistakenly considered to involve mucoceles, pyoceles
      or osteomyelitis. The present study reports the case of a 66-year-old male with
      squamous cell carcinoma originating in the frontal sinus. The presenting symptoms
      were a cutaneous nodule on the left side of the forehead and a gradually
      progressive headache. Magnetic resonance imaging (MRI) demonstrated erosion of
      the ethmoid sinus, frontal lobe and orbit. The radical resection under frontal
      craniotomy was performed followed by post-operative radiotherapy. Six months
      after the surgery, the MRI examinations did not find any recurrence, and the
      patient currently lives symptom-free. The present study illustrates that frontal
      sinus cancer should be diagnosed early with caution. Total surgical resection
      followed by radiotherapy and chemotherapy, used singly or in combination, may
      result in favorable outcomes. The current study discusses the diagnosis,
      treatment and prognosis of the present case and reviews the associated literature
      to emphasize the importance of an early identification of this rare disease.

PMID- 24932259
TI  - Non-invasive imaging of Toll-like receptor 5 expression using 131I-labeled mAb in
      the mice bearing H22 tumors.
AB  - Toll-like receptor 5 (TLR5) is overexpressed in several cancers and metastases,
      and presents an enticing target for molecular imaging of primary tumors. In the
      present study, 131I-anti-TLR5 monoclonal antibody (mAb) was evaluated for its use
      as a novel radiotracer for imaging hepatocarcinoma in mice bearing H22 tumors.
      The expression of TLR5 was analyzed by quantitative polymerase chain reaction and
      immunohistochemistry. The anti-TLR5 mAb and isotype immunoglobulin G (IgG) were
      radiolabeled with iodine-131 by the Iodogen method. The in vitro stability of
      iodinalized probes was determined in serum or saline for a series of times, and
      then evaluated with radio-thin-layer chromatography. The biodistribution study
      and autoradiography were performed in H22 tumor-bearing mice. It was found that
      H22-xenografted tumor tissue exhibited a higher level of TLR5 expression compared
      with normal liver tissues. 131I-anti-TLR5 mAb and 131I-IgG were obtained
      subsequent to purification, with high radiochemical purity (>95%), and remained
      stable for 48 h in human serum. The target-to-non-target ratio in the 131I-anti
      TLR5 mAb group was significantly higher compared with the 131I-IgG group. The
      biodistribution study and autoradiography demonstrated that 131I-anti-TLR5 mAb
      was specifically retained in hepatocarcinoma with a high tumor uptake.
      Altogether, these results show that 131I-anti-TLR5 mAb is capable of detecting
      lesions in a TLR5-expressing tumor, with high target selectivity, and may offer a
      promising agent for hepatocarcinoma diagnosis and encourage further
      investigation.

PMID- 24932260
TI  - Primary gastrointestinal stromal tumor of the prostate: A case report and
      literature review.
AB  - Extragastrointestinal stromal tumors (EGISTs) are relatively rare soft tissue
      neoplasms arising from the extra gastrointestinal tract. The current study
      presents a case of primary EGIST of the prostate observed in a 55-year-old male.
      Imaging studies showed a 10*10.5*9.5-cm prostate mass. On histological
      observation, the mass was separated from the rectum serosa and exhibited a high
      mitotic count (8/50 high-power fields). The results of immunohistochemical
      staining showed positive immunoreactivity for cluster of differentiation (CD)117
      (c-kit), CD34 and DOG1 in the tumor. On mutation analysis, loss of heterozygosity
      of the c-kit gene was observed in the prostatic EGIST; however, the platelet
      derived growth factor receptor-alpha (PDGFRA) gene was considered to be normal.
      Therefore, as EGIST of the prostate is rare, there is a requirement for the
      confirmation of the diagnosis to be based on immunohistochemistry and mutation
      analysis (of c-kit and PDGFRA).

PMID- 24932261
TI  - Mixed lineage leukemia-septin 5 fusion transcript in de novo adult acute myeloid
      leukemia with t(11;22)(q23;q11.2): A case report.
AB  - The current report presents a case of de novo acute myeloid leukemia (AML) in a
      32-year-old male. Cytogenetic analysis showed that the karyotype of the bone
      marrow cells was as follows: 46,XY,t(11;22)(q23;q11.2)[13]/46,X,
      Y,+10,t(11;22)(q23;q11.2)[7]/47,XY,+10,t(11;22)(q23;q11.2)[1]/46,XY[1].
      Fluorescence in situ hybridization analysis using a mixed lineage leukemia (MLL)
      specific probe showed a split in the MLL gene. Reverse transcription polymerase
      chain reaction (PCR) analysis demonstrated an MLL-septin 5 (SEPT5) fusion
      transcript in the patient. Nucleotide sequencing analysis of the PCR product
      confirmed the fusion between the MLL exon 9 and SEPT5 exon 3, and the product was
      521 bp in length. The present study reviewed the clinical and molecular features
      of the AML with an MLL-SEPT5 fusion gene.

PMID- 24932262
TI  - Recurrent huge leiomyoma of the urethra in a female patient: A case report.
AB  - Urethral leiomyoma is an extremely rare condition that arises from the smooth
      muscle of the urethra. To the best of our knowledge, there is only a single
      reported recurrence treated by a repeat excision in the literature to date. The
      present study reports an exceptionally rare case of a recurrent huge leiomyoma of
      the female urethra. The 47-year-old female was diagnosed with a huge mass located
      between the urethra and vagina during a gynecological examination. The patient
      had no symptoms and was successfully treated with transabdominal excision.
      Pathological examinations revealed a leiomyoma of the urethra. The patient was
      followed up for one year without any sign of recurrence.

PMID- 24932264
TI  - Adenosquamous carcinoma of the conjunctiva: A case report.
AB  - Adenosquamous carcinoma (ASC) is a rare form of malignancy which consists of two
      types of cell, including squamous cells and glandular-like cells. The current
      report presents the first known case of ASC in the conjunctiva and analyzes the
      histological findings. A 76-year-old female presented with right eyelid swelling
      in 2001. A right conjunctival tumor was noted and a biopsy was performed.
      Histologically, the tumor was diagnosed as a squamous cell carcinoma. The patient
      underwent radiotherapy, but the tumor rapidly relapsed. Subsequently, the patient
      underwent orbital exenteration. Histologically, the conjunctival tissues had been
      replaced with invasive tumor cells. A number of tumor cells demonstrated squamous
      differentiation with a keratinizing tendency, while other tumor cells exhibited
      mucin-producing activity with glandular formation. The conjunctival tumor was
      diagnosed as an ASC. At the time of writing, the patient is well without local
      recurrence or distant metastases. ASC typically exhibits aggressive biological
      behavior, and is associated with worse prognosis than conventional
      adenocarcinoma. Therefore, complete surgical excision is considered a key
      treatment for ASC of the conjunctiva.

PMID- 24932263
TI  - Slug overexpression induces stemness and promotes hepatocellular carcinoma cell
      invasion and metastasis.
AB  - Detection of metastasis of hepatocellular carcinoma (HCC) is crucial for early
      diagnosis. Epithelial-mesenchymal transition (EMT) is a common event in the
      metastasis of tumor cells. Slug and Snail are homologous proteins, which play an
      important role in EMT. The present study aimed to investigate whether Slug and
      Snail overexpression is associated with the invasiveness of HCC in vitro and in
      vivo. Invasion, colony formation and wound healing assays, as well as flow
      cytometry analysis, were performed to examine the invasiveness and proliferation
      capabilities of HepG2 cells following transfection with cNDA or the siRNA of Slug
      or Snail. The effects of Slug on HCC in vivo were examined using a xenograft
      model. Slug upregulation increased the percentage of cluster of differentiation
      (CD)133+ cells among HepG2 cells, and induced cell invasion and proliferation;
      whereas Snail upregulation did not affect the cells in vitro. The Slug
      overexpression group exhibited the highest rate of tumor growth compared with the
      Snail overexpression and control groups in vivo. These findings demonstrated that
      Slug increases the percentage of CD133+ cells, promotes the clonigenicity of HCC
      cells and induces a stronger stemness in Slug-overexpressing cells. These changes
      activate dormant developmental pathways in invading tumor cells. Thus, Slug may
      serve as a novel target for HCC prognosis and therapy.

PMID- 24932265
TI  - Immunohistochemical expression of estrogen and progesterone receptors in
      endometrial polyps: A comparison between benign and malignant polyps in
      postmenopausal patients.
AB  - The aim of the present study was to evaluate estrogen receptor (ER) and
      progesterone receptor (PR) expression in the glandular epithelium and stroma of
      benign and malignant endometrial polyps of postmenopausal patients. A total of
      1,050 females underwent surgical hysteroscopy at the Professor Dr Jose Aristodemo
      Pinotti Women's Hospital, Center for Integral Attention to Women's Health of the
      State University of Campinas, between January 1998 and December 2008. Of the
      total number, 390 postmenopausal females with endometrial polyps were included in
      the study. Polypoid lesions were histologically classified as benign lesions
      (endometrial polyps and polyps with non-atypical simple hyperplasia or non
      atypical complex hyperplasia) and premalignant and malignant lesions (polyps with
      atypical simple hyperplasia or atypical complex hyperplasia and carcinomatous
      polyps). ER and PR expression was evaluated by immunohistochemistry according to
      cell staining, intensity of nuclear staining and final score. The final score for
      receptor expression was compared between the benign and premalignant/malignant
      polyps. The prevalence of malignancy in endometrial polyps was 7.1% and was
      associated with postmenopausal bleeding. Only the final score for ER expression
      in the stroma of endometrial polyps was higher in the benign group than in the
      premalignant/malignant group, and this difference was significant. However, no
      difference was identified in PR expression. In addition, the risk of malignancy
      in endometrial polyps was significantly higher when the expression of ER and PR
      was negative in the stromal component of the polyp (P<0.01). The malignancy of
      endometrial polyps was also associated with a low expression of stromal ER,
      however, PR expression did not show any association with the risk of malignancy.

PMID- 24932266
TI  - Trastuzumab monotherapy for bone marrow metastasis of breast cancer: A case
      report.
AB  - The current study presents the case of a 41-year-old female patient who received
      modified radical mastectomy and adjuvant chemotherapy and radiotherapy for
      infiltrating ductal cancer of the left breast. The pathological stage of the
      disease was IIA. In addition, the patient was negative for the estrogen and
      progesterone receptors, and human epidermal growth factor receptor-2 gene
      amplification was identified. At one year following surgery, the patient
      presented with severe pancytopenia and pain at multiple sites all over the body.
      Furthermore, the patient's Eastern Cooperative Oncology Group performance status
      score was 3 and numeric rating scale pain score was 8. The bone marrow puncture
      indicated bone marrow metastatic cancer, and the positron emission
      tomography/computed tomography (CT) indicated multiple internal organ metastases
      and osseous metastasis. Chemotherapy treatment posed great risks due to the
      patient's poor performance status and severe bone marrow suppression. Therefore,
      trastuzumab monotherapy was administered at a loading dose of 8 mg/kg and a
      maintenance dose of 6 mg/kg every three weeks. Following four doses of
      trastuzumab treatment, the patient's performance status significantly improved
      and the peripheral blood cell counts had returned to within the normal ranges.
      Taxol was added to the trastuzumab treatment and seven cycles were completed. No
      metastatic cancer cells were found in the subsequent bone marrow smear test;
      however, CT showed metastatic foci in the left lung. Furthermore, the enlarged
      lymph nodes had subsided and the tumor in the right appendix region had decreased
      in size by 50%. The patient's disease condition was maintained stable for 11
      months.

PMID- 24932267
TI  - Evaluation of chromosome 17 polysomy in breast cancer by FISH analysis of whole
      nuclei, and its clinicopathological significance.
AB  - Human epidermal growth factor receptor 2 (HER2) amplification and overexpression
      are associated with poor prognosis and resistance to cytotoxic drugs in patients
      with breast cancer. Increases in the number of HER2 gene copies have been shown
      to be associated with chromosome 17 polysomy. The use of whole, intact nuclei for
      fluorescence in situ hybridization (FISH) assay improves the accuracy of the
      results. FISH analysis of whole nuclei (WNFISH) and immunohistochemistry (IHC)
      were used to analyze HER2 gene amplification and HER2 protein expression in 109
      breast cancer specimens. Chromosome 17 polysomy and its correlations with HER2
      gene amplification, HER2 protein expression and the clinicopathological outcomes
      of the patients were also investigated. Among the 109 cases, WNFISH detected HER2
      amplification in 30 cases, equivocal amplification in 19 cases and no
      amplification in 60 cases. WNFISH detected chromosome 17 centromere (CEP17)
      polysomy in 37 cases and no polysomy in 72 cases. Among the 109 cases assessed by
      tissue microarray and IHC, 31 cases were HER2-negative, 14 cases were scored 1+,
      23 cases were scored 2+ and 41 cases were scored 3+. The results demonstrated
      that in the cases with chromosome 17 polysomy, the HER2 gene was amplified, HER2
      protein expression was increased and the incidences of nuclear atypia and lymph
      node metastases were higher compared with those in the cases without chromosome
      17 polysomy. Chromosome 17 polysomy may correlate with increased malignant
      potential and metastatic spread in breast cancer.

PMID- 24932268
TI  - Pilomatrix carcinoma of the scalp with pulmonary metastasis: A case report of a
      complete response to oral endoxan and etoposide.
AB  - Pilomatrix carcinoma is an extremely rare skin tumor derived from basaloid cells
      in the hair follicles; it often exhibits locally aggressive behavior with a
      tendency toward local recurrence. The average age of occurrence is 45 years, and
      there appears to be a male to female incidence ratio of 4:1. Although pilomatrix
      carcinomas are predominantly identified in the neck and scalp, there are studies
      in the literature reporting other tumor development sites, including the upper
      extremities, torso and popliteal fossa. If diagnosed at an early stage, this
      malignant tumor is generally treated with wide surgical resection. However, for
      the advanced-stage tumors, there are no standard treatment procedures known to
      produce good results. The current study presents the case of a 76-year-old male
      with pilomatrix carcinoma originating from the scalp with metastases to the lung.
      The patient had a rapid and complete clinical response following an oral
      combination chemotherapy regimen of cyclophosphamide and etoposide.

PMID- 24932269
TI  - Primary osteosarcoma of the breast: A case report.
AB  - Osteosarcoma (OS) located in the breast is an extremely rare, malignant neoplasm.
      The current study presents the diagnostic process, treatment and follow-up of a
      67-year-old female with OS of the breast. The diagnosis was made according to
      diagnostic imaging methods and microscopic examination with additional
      immunohistochemical staining. As a surgical treatment, tumourectomy with
      intraoperative histological examination and simple breast amputation was
      performed. No adjuvant chemotherapy was administered following surgery. Lung and
      bone metastases occurred without local recurrence 14 months following the
      surgery. In the present study, the details of the diagnostic examinations
      performed are evaluated and the consecutive phases of diagnostic and therapeutic
      proceedings are examined in comparison with the knowledge in the literature.

PMID- 24932270
TI  - An intraosseous malignant peripheral nerve sheath tumor of the lumbar spine
      without neurofibromatosis: Case report and review of the literature.
AB  - A malignant peripheral nerve sheath tumor (MPNST) is defined as any malignant
      tumor that develops or differentiates from cells in the peripheral nerve sheath.
      This tumor is commonly associated with neurofibromatosis type 1 (NF1) and
      previous radiotherapy treatment. Primary intraosseous MPNSTs are extremely rare
      and a case of the lumbar spine in a patient without NF1 is reported in the
      present study, with a review of the intraosseous MPNST literature. A 45-year-old
      female presented with a 1-month history of severe lower back pain and pain
      radiating to the left leg. A total en bloc spondylectomy of L4 was performed. The
      postoperative histopathological diagnosis was MPNST with deletion of NF1,
      confirmed by dual-color fluorescence in situ hybridization (FISH) analysis. The
      tumor recurred 1 month following the surgery. Although adjuvant chemotherapy was
      administered, the patient succumbed due to intramedullary dissemination and
      carcinomatous meningitis 8 months following the initial consultation. NF1
      deletion by FISH analysis may be particularly useful in distinguishing MPNST from
      other high-grade malignancies with overlapping morphological features.

PMID- 24932271
TI  - Primary retroperitoneal extraskeletal mesenchymal chondrosarcoma involving the
      vena cava: A case report.
AB  - The current study presents a case of extraskeletal mesenchymal chondrosarcoma
      (ESMC) involving the vena cava that originally occurred in the retroperitoneum of
      a 61-year-old female. Following excision of the masses, pathological examination
      confirmed a diagnosis of primary ESMC. Mesenchymal chondrosarcomas are extremely
      rare in comparison to conventional chondrosarcomas and even more so when arising
      in an extraskeletal location. In the current report, the major characteristics of
      ESMC are discussed and a review of the current knowledge regarding this rare
      disease entity is presented.

PMID- 24932272
TI  - Solitary fibrous tumor of the soft palate: A report of two cases.
AB  - Solitary fibrous tumors (SFTs) are a unique group of mesenchymal neoplasms of
      fibroblastic or myofibroblastic origin and are extremely rare in the oral cavity.
      The present study reported two additional cases of SFTs in the soft palate, along
      with the computed tomography characteristics, which demonstrated well
      circumscribed soft tissue lesions with marked and homogenous enhancement.
      Following wide resection, one of the cases showed certain malignant pathological
      characteristics, including infiltration of mucinous gland, hypercellularity,
      nuclear atypia and weak positive staining for S-100. In our experience, SFTs
      should be considered as a differential diagnosis when a well-circumscribed and
      solid mass in the soft palate is identified.

PMID- 24932273
TI  - Epithelial-myoepithelial carcinoma of the hypopharynx: A rare case.
AB  - Epithelial-myoepithelial carcinoma (EMC) is a rare neoplasm, which predominantly
      arises in the parotid gland. EMC is characterized by two types of cells;
      myoepithelial and epithelial cells arranged in well-defined tubules. A 48-year
      old male with a six-month history of dysphagia presented with a 2-cm-diameter
      mass in the left posterior wall of the hypopharynx. Histopathological examination
      revealed that the tumor cells were arranged in duct-like structures with an inner
      layer of ductal cells and an outer layer of clear cells. Immunohistochemically,
      the outer layer of clear cells stained positive for calponin, p63 protein, glial
      fibrillary acidic protein, S-100 protein and smooth muscle actin, which is
      consistent with a myoepithelial phenotype. The inner layer stained positive for
      cytokeratin and cytokeratin-7, which is consistent with an epithelial phenotype.
      The tumor was excised and no recurrence or metastasis was found 27 months
      following surgery. To the best of our knowledge, this is the first case of EMC
      described that has arisen from the hypopharynx.

PMID- 24932274
TI  - A recurrent sialolipoma of the parotid gland: A case report.
AB  - Sialolipoma is a rare benign neoplasm and was recently described as a
      histological variant of intraoral lipoma. In the current report, the case of a of
      a 65-year-old female with a slow-growing mass in the right parotid gland with
      recurrence is presented. The initial clinical diagnosis was a benign salivary
      gland tumor. The tumor was situated between the right parotid gland and the right
      masseter muscle; therefore, a superficial parotidectomy was performed.
      Histopathology revealed that the tumor was a sialolipoma of the parotid gland.
      During the three-month follow-up, a recurrent right parotid tumor was identified
      in the deep lobe space of the right parotid gland and a deep lobe parotidectomy
      was performed. The present case demonstrates that although surgical excision is
      generally sufficient to treat parotid gland sialolipoma, postoperative follow-up
      is required as multifocal lesions may potentially remain, which could result in
      recurrence.

PMID- 24932275
TI  - Intrathoracic extramedullary hematopoiesis mimicking intrathoracic tumors: A case
      report.
AB  - Extramedullary hematopoiesis (EMH) is a rare disease that is characterized by the
      presence of hemopoietic tissue outside the bone marrow. The masses that form are
      usually microscopic and asymptomatic, but occasionally lead to tumor-like masses.
      A 56-year-old male who initially presented to the First Affiliated Hospital,
      School of Medicine, Zhejiang University (Hangzhou, China) with upper abdominal
      pain and jaundice was found to have paravertebral masses in the thorax.
      Histopathological examination of a computed tomography-guided needle aspiration
      biopsy of the masses revealed EMH. The current study presents this unusual case,
      in which EMH was diagnosed by chance in a patient with hereditary spherocytosis.
      As the intrathoracic EMH was asymptomatic, the patient was discharged with the
      proviso of regular follow-up examinations. The patient exhibited improved blood
      cell counts following a splenectomy to reduce the hemolysis and stabilize the
      thoracic masses. The thoracic masses have been closely followed for one and a
      half years. A correct diagnosis can thus aid in avoiding unnecessary surgical
      intervention, particularly in an asymptomatic patient.

PMID- 24932277
TI  - Sorbitol induces apoptosis of human colorectal cancer cells via p38 MAPK signal
      transduction.
AB  - Sorbitol has been reported to have anticancer effects in several tumor models,
      however its effects on colorectal cancer remain elusive. In the present study,
      the effects of sorbitol on growth inhibition and apoptosis in the colorectal
      cancer HCT116 cell line were evaluated and its mechanism of action was examined.
      An MTT assay was utilized to determine the effect of sorbitol on HCT116 cell
      proliferation at different time points and variable doses. Western blot analysis
      was used to examine the effect of sorbitol on apoptosis-related protein
      expression and the p38 MAPK signaling pathway. The results revealed that sorbitol
      may inhibit the growth of HCT116 cells in a time- and dose-dependent manner.
      Following treatment with sorbitol for 3 h, western blotting demonstrated cleavage
      of the caspase-3 zymogen protein and a cleavage product of poly (ADP-ribose)
      polymerase (PARP), a known substrate of caspase-3, was also evident. During
      sorbitol-induced apoptosis, the mitochondrial pathway was activated by a dose
      dependent increase in Bax expression and cytochrome c release, while the
      expression of anti-apoptotic protein Bcl-2 was significantly decreased in a dose
      dependent manner. The investigation for the downstream signal pathway revealed
      that sorbitol-induced apoptosis was mediated by an increase in phosphorylated p38
      MAPK expression. Overall, the observations from the present study imply that
      sorbitol causes increased levels of Bax in response to p38 MAPK signaling, which
      results in the initiation of the mitochondrial death cascade. Therefore, sorbitol
      is a promising candidate as a potential chemotherapeutic agent for the treatment
      of colorectal cancer HCT116 cells.

PMID- 24932276
TI  - Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage
      glottic cancer: A dosimetrical analysis.
AB  - Previous studies on advanced radiotherapy (RT) techniques for early stage glottic
      cancer have focused on sparing the carotid artery. However, the aim of the
      present study was to evaluate the dosimetric advantages of volumetric modulated
      arc therapy (VMAT) in terms of sparing the thyroid gland in early-stage glottic
      cancer patients. In total, 15 cT1N0M0 glottic cancer patients treated with
      definitive RT using VMAT were selected, and for dosimetric comparison, a
      conventional RT plan comprising opposed-lateral wedged fields was generated for
      each patient. The carotid artery, thyroid gland and spinal cord were considered
      organs at risk. The prescription dose was 63 Gy at 2.25 Gy per fraction. For the
      thyroid gland and carotid artery, all compared parameters were significantly
      lower with VMAT compared with conventional RT. For the thyroid gland, the median
      reduction rates of the mean dose (Dmean), the volume receiving >=30% of the
      prescription dose (V30) and the V50 were 32.6, 40.9 and 46.0%, respectively. The
      Dmean was 14.7+/-2.6 Gy when using VMAT compared with 22.2+/-3.9 Gy when using
      conventional RT. The differences between the techniques in terms of planning
      target volume coverage and dose homogeneity were not significant. When
      considering a recent normal tissue complication probability model, which
      indicated the mean thyroid gland dose as the most significant predictor of
      radiation-induced hypothyroidism, the dosimetric advantage shown in this study
      may be valuable in reducing hypothyroidism following RT for early stage glottic
      cancer patients.

PMID- 24932278
TI  - Comparison of the efficacy and safety of denosumab versus bisphosphonates in
      breast cancer and bone metastases treatment: A meta-analysis of randomized
      controlled trials.
AB  - Breast cancer is the most common type of cancer in females worldwide. Patients
      with breast cancer and bone metastases may experience increased osteoclast
      activity, resulting in local bone destruction and skeletal complications,
      including pain, hypercalcemia and skeletal-related events. Intravenous
      bisphosphonates (BPs) are the standard treatment administered to patients with
      breast cancer and bone metastases to prevent skeletal-related events. However, in
      certain patients, BPs may cause renal toxicity, acute-phase reactions and
      osteonecrosis of the jaw. More effective, safer and more tolerable therapies,
      which prevent bone destruction and skeletal complications, are required in order
      to improve patient quality of life. Denosumab is a fully human monoclonal
      antibody that binds to and neutralizes receptor activator of nuclear factor
      kappaB ligand, which is a key mediator in the pathogenesis of a broad range of
      skeletal diseases, thereby inhibiting osteoclast function and bone resorption.
      Therefore, we conducted a meta-analysis to compare both the safety and efficacy
      of denosumab and BPs in the treatment of breast cancer and bone metastases. Five
      databases, two clinical trial registry platforms and reference lists of relevant
      papers were analyzed. The meta-analysis concluded that denosumab was more
      effective at preventing pain and skeletal-related events than BPs, in patients
      with breast cancer and bone metastases. Patients receiving denosumab demonstrated
      a higher level of clinical improvement in terms of health-related quality of life
      than patients receiving BPs. Compared with BPs, denosumab reduced the incidence
      of certain indicators of adverse events, including pyrexia, bone pain, edema and
      renal failure.

PMID- 24932279
TI  - Benefits of skin biopsy of senile hemangioma in intravascular large B-cell
      lymphoma: A case report and review of the literature.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of B-cell lymphoma
      characterized by selective growth of clonal B-cells in the lumen of the small
      vessels of various organs including the liver, spleen, lungs, skin, brain, and
      kidney. An 86-year-old male presented with weight loss, fever and night sweats
      (known as B symptoms). Blood examination revealed pancytopenia, high lactate
      dehydrogenase and high soluble interleukin-2 receptor, suggesting hematopoietic
      malignancy. However, there were no abnormal hematopoietic cells in the peripheral
      blood. No lymph node swelling was identified on examination by whole-body
      computed tomography scan. Therefore, IVLBCL was suspected, and random skin
      biopsies and a skin biopsy from a senile hemangioma were carried out. A small
      number of large atypical lymphoid cells resided in the small blood vessels in the
      deep dermis and subcutaneous tissue of the random skin biopsies, and numerous
      atypical lymphoid cells were identified in the small vessels of the senile
      hemangioma. These results suggest the usefulness of skin biopsy from senile
      hemangiomas in the diagnosis of IVLBCL.

PMID- 24932280
TI  - The haplotype of three polymorphisms in the SATB1 promoter region impacts
      survival in breast cancer patients.
AB  - Special AT-rich sequence binding protein 1 (SATB1) has regulatory effects on gene
      expression and appears to play an important role in tumor progression. The
      present study screened the promoter region of the SATB1 gene for polymorphisms,
      evaluated the corresponding haplotypes regarding alterations in promoter activity
      in vitro and analyzed the impact of these haplotypes on the clinical course of
      breast cancer patients. A cohort of 241 female Caucasian breast cancer patients
      who had been treated was enrolled in this retrospective analysis. The median
      follow-up time was 93 months (range, 4-155 months). PCR products from DNA of 10
      healthy, unrelated volunteers were analyzed to identify new polymorphisms within
      the promoter region. Genotyping was conducted using restriction fragment length
      polymorphism and pyrosequencing. PCR constructs with the respective alleles from
      the four most frequent haplotypes were cloned into the vector pGEM(r)-T Easy and
      then transferred into the luc2-containing reporter vector pGl 4.10(r) for
      transfection of HEK293 cells. The pGl 4.73(r) vector, containing hRluc, was used
      for normalizing the transfection rates. Sequencing the region -3807 to -2828 bp
      upstream of ATG from ten healthy blood donors, three single nucleotide
      polymorphisms consisting of base exchanges were identified: -3600T>C, -3363A>G
      and -2984C>T. The SATB1 -3600T/-3363A/-2984C haplotype had lower promoter
      activity than all other constructs in vitro and exhibited a significant
      association with nodal status (P<0.05). Kaplan-Meier survival analysis revealed
      significantly improved overall survival for homozygous SATB1 -3600T/-3363A/-2984C
      haplotype carriers compared with heterozygous carriers or the other haplotypes
      (P=0.033). The SATB1 -3600T/-3363A/-2984C haplotype is associated with lower
      promoter activity and appears to impact upon survival in breast cancer patients.

PMID- 24932281
TI  - Diagnostic role of fluorodeoxyglucose positron emission tomography-computed
      tomography in prostate cancer.
AB  - The role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography
      (PET)-computed tomography (CT) in prostate cancer remains controversial due to a
      limited number of previous clinical investigations. The aim of the present
      retrospective study was to assess the diagnostic value of FDG PET-CT in prostate
      cancer, with an emphasis on the detection of metastatic disease. Twenty-five
      relevant cases of patients with newly diagnosed prostate cancer, referred for
      staging, or with a history of prostate cancer or recent prostate specific antigen
      (PSA) relapse, referred for the detection of metastatic disease, were included in
      the present study. None of the patients had known imaging or pathological
      evidence of metastatic disease prior to FDG PET-CT, however, the PSA levels had
      been recorded in all patients in the two months prior to FDG PET-CT imaging.
      Verification of the FDG PET-CT observations was made by biopsy, regional
      diagnostic CT and/or whole-body bone scintigraphy. The sensitivity of FDG PET-CT
      in identifying untreated primary lesions was only 33% (3/9). However, FDG PET-CT
      detected metastatic disease in six of the nine patients who underwent initial
      staging. Out of 16 patients with previous treatments and recent PSA relapse, FDG
      PET-CT successfully identified metastatic diseases in 12 and tumor recurrence
      within the prostatic fossa of two patients. The difference in the PSA levels was
      identified to be statistically significant between the FDG PET-CT-positive and 
      negative subgroups of the 16 restaging patients. The results indicated that FDG
      PET-CT is not useful for the diagnosis of prostate cancer, but may aid with the
      detection of metastatic disease in appropriately selected patients.

PMID- 24932283
TI  - Casticin inhibits self-renewal of liver cancer stem cells from the MHCC97 cell
      line.
AB  - Casticin exerts anticarcinogenic activity in several types of cancers, including
      human hepatocellular carcinoma (HCC). The aim of the present study was to
      investigate the effects of casticin, which is derived from Fructus Viticis
      Simplicifoliae, on the self-renewal capacity of liver cancer stem cells (LCSCs)
      derived from the HCC MHCC97 cell line. The present study demonstrated that
      casticin significantly inhibited the proliferation of LCSCs from the MHCC97 cell
      line in a dose-dependent manner (P<0.05), the half maximal inhibitory
      concentration of the parental cells and LCSCs was 17.9 and 0.5 MUmol/l,
      respectively. Furthermore, casticin reduced the sphere-forming capacity of LCSCs
      and downregulated beta-catenin protein expression in a concentration-dependent
      manner. Lithium chloride, an agonist known to activate the Wnt/beta-catenin
      signaling pathway, attenuated the casticin-induced downregulation of beta-catenin
      protein expression and inhibited the self-renewal capacity. To the best of our
      knowledge, the present study is the first to demonstrate that casticin
      effectively eradicates LCSCs and beta-catenin was identified as the potential
      target. Thus, casticin may offer a novel therapeutic approach for the treatment
      of HCC.

PMID- 24932282
TI  - EGFR, PIK3CA, KRAS and BRAF mutations in meningiomas.
AB  - Meningiomas are among the most frequent intracranial tumors. Treatment involves
      surgical resection with optional subsequent radiotherapy for high-grade
      meningiomas or radiosurgery following incomplete tumor removal. At present, no
      pharmacological agents are used as treatment. The use of targeted therapies has
      been considered, and specific therapies, including anti-EGFR treatment, have been
      clinically tested. The experience from the treatment of various types of cancers
      shows that patient outcome depends on the mutational status of particular
      molecules, including epithelial growth factor receptor (EGFR), Kirsten rat
      sarcoma viral oncogene homolog (KRAS), v-Raf murine sarcoma viral oncogene
      homolog B1 (BRAF) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic
      subunit alpha (PIK3CA). Therefore, the aim of the present study was to assess the
      occurrence and potential use of these markers in patients with meningioma. In
      total, 55 formalin-fixed, paraffin-embedded meningioma samples were subjected to
      genomic sequencing of EGFR (exons 18-21), KRAS (exon 1), BRAF (exon 15) and PI3K
      (exons 9, 20). No mutations were identified in EGFR, KRAS or BRAF. Point
      mutations in PIK3CA were revealed in the samples of two patients with atypical
      and anaplastic meningiomas. Although these mutations appear to be rare, this
      result, along with previously reported findings, indicates that the PI3K/protein
      kinase B pathway may serve as a more reasonable molecular target for meningioma
      than EGFR.

PMID- 24932284
TI  - Identification of microRNA profiles in salivary adenoid cystic carcinoma cells
      during metastatic progression.
AB  - Salivary adenoid cystic carcinoma (SACC) is a common type of salivary gland
      cancer. The poor long-term prognosis of patients with SACC is primarily due to
      local recurrence, distant metastasis and perineural invasion. MicroRNAs (miRNAs)
      have been identified as important post-transcriptional regulators, which are
      involved in various biological processes. The aim of the present study was to
      identify the miRNA expression profiles that are involved in the metastatic
      progression of SACC. Therefore, microarray technology was employed to identify
      miRNA expression profiles in an SACC cell line, ACC-2, and a highly metastatic
      SACC cell line, ACC-M, which was screened from ACC-2 by a combination of in vivo
      selection and cloning in vitro. Differences in miRNA expression were assessed by
      quantitative polymerase chain reaction (qPCR) assay. In addition, the potential
      target genes that are regulated by selected miRNAs were analyzed by various
      target prediction tools. The microarray data revealed that the levels of 38
      miRNAs significantly differed between the ACC-M cells and the control ACC-2
      cells. Six miRNAs (miR-4487, -4430, -486-3p, -5191, -3131 and -211-3p) were
      selected to validate the microarray data via qPCR. The expression of two miRNAs
      (miR-4487 and -4430) was significantly upregulated in the ACC-M cells, while the
      expression of two other miRNAs (miR-5191 and -3131) was significantly
      downregulated in the ACC-M cells. The potential target genes that were identified
      to be controlled by the six selected miRNAs were divided into four groups
      according to function, as follows: Apoptosis and proliferation (46 genes), cell
      cycle (30 genes), DNA damage and repair (24 genes) and signaling pathway (30
      genes). The identification of microRNA expression profiles in highly metastatic
      SACC cells may provide an improved understanding of the mechanisms involved in
      metastatic progression, which would aid in the development of novel strategies
      for the treatment of SACC.

PMID- 24932285
TI  - Association between the low-dose irinotecan regimen-induced occurrence of grade 4
      neutropenia and genetic variants of UGT1A1 in patients with gynecological
      cancers.
AB  - The occurrence of severe neutropenia during treatment with irinotecan (CPT-11) is
      associated with the *6 and *28 alleles of uridine diphosphate
      glucuronosyltransferase 1A1 (UGT1A1). However, the correlation between these
      variants and the occurrence of severe neutropenia in a low-dose CPT-11 regimen
      for the treatment of gynecological cancers has not been extensively studied.
      There are also no studies regarding the association between the 421C>A mutation
      in ATP-binding cassette sub-family G member 2 (ABCG2) and the occurrence of
      severe neutropenia in CPT-11-treated patients with gynecological cancers. The
      present study was designed to determine the factors associated with the
      occurrence of grade 4 neutropenia during chemotherapy for gynecological cancers
      with combinations of CPT-11 and cisplatin or mitomycin C. In total, 44 patients
      with gynecological cancer were enrolled in the study. The association between the
      absolute neutrophil count (ANC) nadir values, the total dose of CPT-11 and the
      genotypes of UGT1A1 or ABCG2 was studied. No correlation was observed between the
      ANC nadir values and the total dose of CPT-11. The ANC nadir values in the
      UGT1A1*6/*28 and *6/*6 groups were significantly lower compared with those in the
      *1/*1 group (P<0.01). Univariate analysis showed no association between the
      occurrence of grade 4 neutropenia and the ABCG2 421C>A mutation. Subsequent to
      narrowing the factors by univariate analysis, multivariate logistic regression
      analysis only detected significant correlations between the occurrence of grade 4
      neutropenia and the UGT1A1*6/*6 and *6/*28 groups (P=0.029; odds ratio, 6.90; 95%
      confidence interval, 1.22-38.99). No associations were detected between the
      occurrence of grade 4 neutropenia and the heterozygous variant (*1/*6 or *1/*28)
      genotype, type of regimen or age. In conclusion, the UGT1A1*6/*28 and *6/*6
      genotypes were found to be associated with the occurrence of severe neutropenia
      in the low-dose CPT-11 regimen for gynecological cancers. This finding indicates
      that the determination of UGT1A1 variants may be as useful in CPT-11 chemotherapy
      for gynecological conditions as it is in colorectal and lung cancer patients
      treated with this drug.

PMID- 24932286
TI  - Fascin upregulation in primary head and neck squamous cell carcinoma is
      associated with lymphatic metastasis.
AB  - Fascin is an actin-bundling protein that is associated with cellular motility and
      cancer-cell invasion. The present study aimed to examine the expression of fascin
      in head and neck squamous cell carcinoma (HNSCC) and its potential use as a
      biomarker. In a prospective study with a median follow-up time of 48.8 months,
      tumor tissues, adjacent healthy tissues and cervical lymph node metastases were
      collected from 25 patients and analyzed by immunohistochemistry. The specimens
      were scored according to the intensity of fascin staining and the percentage of
      tumor cells stained using a semi-quantitative scoring approach; the data were
      analyzed and correlated with clinical follow-up observations. All of the
      investigators were blinded to the origin of the specimens. The expression levels
      of fascin were significantly increased in the tumor tissues (P=0.03) and lymph
      node metastases (P=0.03) compared with that of the normal tissues. The high
      expression level of fascin in the tumor tissues was correlated with the N-status,
      however, not with overall survival. Therefore, fascin may be a suitable marker
      for the prediction of regional lymphatic metastasis in HNSCC.

PMID- 24932287
TI  - Inhibition of ovarian cancer cell proliferation by Pien Tze Huang via the AKT
      mTOR pathway.
AB  - Pien Tze Huang (PZH) is a well-known Chinese medicine that has been used as a
      therapeutic drug in the treatment of a number of diseases, such as hepatocellular
      carcinoma and colon cancer. However, few studies have analyzed the effects of PZH
      on ovarian cancer cell proliferation. In the present study, 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays, cell
      cycle and apoptosis rate analyses and western blotting were conducted to
      investigate the effects of PZH on the proliferation rate of ovarian cancer cells
      and its potential molecular pathway. The results showed that PZH inhibits the
      proliferation of the human ovarian cancer OVCAR-3 cell line by blocking the
      progression of the cell cycle from the G1 to S phase, however, PZH did not induce
      OVCAR-3 cell apoptosis. Increased PZH concentration may downregulate the
      expression of AKT, phosphorylated (p)-AKT, mammalian target of rapamycin (mTOR)
      and p-mTOR proteins in the OVCAR-3 cell line. In addition, it was observed that
      PZH may suppress the protein expression of cyclin-dependent kinase (CDK)4 and
      CDK6. Overall, the results of the present study indicated that PZH may inhibit
      ovarian cancer cell proliferation by modulating the activity of the AKT-mTOR
      pathway.

PMID- 24932288
TI  - Doxorubicin combined with celecoxib inhibits tumor growth of medullary thyroid
      carcinoma in xenografted mice.
AB  - The aim of the present study was to investigate the antitumor effect of celecoxib
      (CXB) combined with doxorubicin (DOX) on the subcutaneous xenograft tumor of
      medullary thyroid carcinoma in nude mice, and to analyze the possible mechanism
      of action. Nude mice with xenografted medullary thyroid carcinoma (MTC) were
      randomly divided into the control, CXB, DOX and DOX plus CXB groups, and the drug
      treatment was administered for three weeks. It was found that the tumor
      inhibition rates and the apoptosis index in the treatment groups were higher than
      in the control group (P<0.01), and that these values were higher in the
      combination group compared with the single-drug group (P<0.01). DOX alone
      upregulated the cyclooxygenase-2 and multidrug-resistance 1 expression levels,
      and the combination of CXB and DOX or CXB alone notably decreased the expression
      level of the two proteins compared with no treatment. The results of the present
      study provide evidence that a combination of DOX and CXB is a potential drug
      candidate for the treatment of MTC.

PMID- 24932289
TI  - Effect of Paris saponin I on radiosensitivity in a gefitinib-resistant lung
      adenocarcinoma cell line.
AB  - Previous studies have observed that Paris saponin I (PSI) exerts a wide range of
      pharmacological activities, including cytotoxic activity against a number of
      malignancies, such as non-small cell lung cancers. The present study aimed to
      investigate the radiosensitization of PSI treatment on a gefitinib-resistant lung
      adenocarcinoma cell line, PC-9-ZD, and its possible mechanism. A 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to
      determine the growth inhibition effect of PSI. A clonogenic assay was performed
      to determine the radiosensitizing effect of PSI treatment on the PC-9-ZD cell
      line. A single-hit multi-target model was used to plot survival curves and
      calculate sensitizing enhancement ratios. The cell cycle was analyzed by flow
      cytometry and cell apoptosis was analyzed with fluorescein-isothiocyanate-Annexin
      V/propidium iodide and Hoechst staining. The expression levels of the proteins
      were detected by western blotting. There was a significant reduction observed in
      the proliferation of the PC-9-ZD cell lines that were treated with PSI. PSI
      enhanced the radiosensitivity of the PC-9-ZD cells with a sensitization
      enhancement ratio of 1.77. Furthermore, PSI induced G2/M arrest and apoptosis of
      the irradiated PC-9-ZD cells. Notably, B-cell lymphoma 2 (Bcl-2) was
      downregulated, and caspase-3, Bcl-2-like protein 4 (Bax) and cyclin-dependent
      kinase inhibitor 1 (P21waf1/cip1) were upregulated by the PSI treatment. The
      present study showed that PSI treatment exhibited potent radiosensitivity against
      gefitinib-resistant PC-9-ZD cells in vitro. This radiosensitivity was associated
      with cell cycle arrest at the G2/M phase, and apoptosis via an increase in
      caspase-3, Bax and P21waf1/cip1 as well as a decrease in Bcl-2 production.

PMID- 24932290
TI  - Effects of silencing RIP1 with siRNA on the biological behavior of the LoVo human
      colon cancer cell line.
AB  - The present study aimed to investigate the effects of silencing RIP1 by small
      interfering RNA (siRNA) on the biological behavior of the LoVo human colorectal
      carcinoma cell line and to provide evidence for the feasibility of colorectal
      cancer gene therapy. LoVo cells were divided into the RIP1 siRNA group, the blank
      control group and the negative control group. Chemically synthesized siRNA
      targeting RIP1 (RIP1 siRNA) was transfected into LoVo cells. Following
      transfection of the RIP1-targeted siRNA into the LoVo cells, the expression of
      the RIP1 gene was effectively inhibited. The results demonstrated that RIP1
      effectively regulated the malignant biological behavior of the LoVo colon cancer
      cell line. Furthermore, the proliferation, motility and invasiveness of LoVo
      cells were inhibited by siRNA knockdown of RIP1. The results revealed that the
      RIP1 gene has an important role in the regulation of proliferation and apoptosis
      in colorectal carcinoma cells.

PMID- 24932291
TI  - Prognostic value of serum leptin in advanced lung adenocarcinoma patients with
      cisplatin/pemetrexed chemotherapy.
AB  - Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in
      lung adenocarcinoma. However, the response to the cisplatin/pemetrexed
      combination varies considerably among patients due to individual variations.
      Thus, novel biomarkers are required to aid the prediction of the response to the
      cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a
      determinant for prognosis in lung adenocarcinoma patients with
      cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung
      adenocarcinoma were obtained for the measurement of leptin and associated tumor
      biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic
      antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4,
      cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression
      were determined by electrochemiluminescence immunoassays. Serum squamous cell
      carcinoma antigen levels were measured using a microparticle enzyme immunoassay.
      The associations between serum leptin and tumor biomarker expression were
      evaluated by Spearman's correlation analysis. Serum CEA, CA19-9, CA15-3, CA125,
      CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients.
      However, a trend towards an improved prognosis was observed in patients with
      lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed
      chemotherapy. The results indicated that the serum leptin level has prognostic
      indications in patients with advanced lung adenocarcinoma during
      cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker
      for the prognosis of cancer patients undergoing chemotherapy treatment.

PMID- 24932292
TI  - Hypertrophic pulmonary osteoarthropathy with primary lung cancer.
AB  - Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome
      that is frequently associated with lung cancer; however, the incidence of
      clinically apparent HPO is not well known. The clinical data of 6,151 patients
      with advanced lung cancer between January 1996 and December 2008 were
      retrospectively analyzed in Zhejiang Cancer Hospital (Hangzhou, China). Data
      pertaining to the presentation of HPO, diagnosis, treatment, pathology, follow-up
      and clinical course were documented. HPO was confirmed using bone scintigraphy by
      the identification of symmetrical, abnormally high uptake in the joints, and/or
      long bones with digital clubbing in the extremities as well as joint pain. The
      clinical characteristics were investigated based on clinical and pathological
      records. The patients were presenting with lung cancer for the first time and had
      not received treatment. Among the 6,151 lung cancer patients, 115 (1.87%)
      demonstrated an abnormally high uptake on bone scintigraphy and digital clubbing
      in the extremities combined with joint pain. A total of 109 patients received
      surgery or chemotherapy treatment and 92 exhibited improved symptoms. The
      improvement rate of HPO was lower in the non-surgery compared with the surgery
      patients (77.4 vs. 91.1%; P=0.049). Bone scintigraphy was repeated in 85 patients
      within 3-6 months, and the HPO symptoms improved in 70 patients. The present
      retrospective study indicated that 1.87% of patients with lung cancer showed
      characteristics that were identified as HPO. The majority of the patient symptoms
      and the bone scintigram of HPO improved as a result of treatment.

PMID- 24932293
TI  - Expression of CXC chemokine receptor-4 and forkhead box 3 in neuroblastoma cells
      and response to chemotherapy.
AB  - Current evidence indicates that the abnormal expression of chemokines or their
      receptors, such as CXC chemokine receptor-4 (CXCR4), is positively correlated
      with the development, progression and metastasis of tumor cells. However, the
      role of CXCR4 in neuroblastoma and its response to chemotherapy remain largely
      unclear. In addition, forkhead box 3 (Foxp3), a transcription factor associated
      with T cell tolerance, is expressed in tumor cells and plays a role in the immune
      evasion of cancers. The present study aimed to examine the expression of CXCR4
      and Foxp3 in the LAN-5 and SK-N-SH neuroblastoma cell lines. The effects of
      chemotherapy drugs, cyclophosphamide (CTX) and pirarubicin (THP), on the
      expression of these two genes were also investigated. Our findings indicated that
      CXCR4 and Foxp3 were highly expressed in LAN-5 and SK-N-SH cells. Following
      treatment with CTX and THP, the protein expression of CXCR4 in LAN-5 and SK-N-SH
      cells was significantly decreased (P<0.05). The expression of Foxp3 in LAN-5
      cells was also significantly downregulated by CTX and THP treatment (P<0.05).
      Therefore, the high expression of CXCR4 and Foxp3 in LAN-5 and SK-N-SH cells and
      their subsequent downregulation following administration of the chemotherapy
      agents suggests that the chemokine receptors, CXCR4 and Foxp3, may be involved in
      the metastasis and tumor evasion of neuroblastoma. Further studies should
      investigate the expression of CXCR4 and Foxp3 in patient samples.

PMID- 24932294
TI  - Misdiagnosed gastrinoma: A case report.
AB  - Gastrinoma is most commonly located in the gastrinoma triangle (comprising of the
      duodenum, pancreas and bile ducts) or in the adjacent lymph nodes. Due to the low
      mortality rate, it is often misdiagnosed as other diseases with similar clinical
      characteristics, such as a solid pseudopapillary tumor of the pancreas (SPTP).
      Therefore, the current study reports a rare case of gastrinoma located in the
      tail of the pancreas of a female patient under medical examination, who exhibited
      no clinical symptoms. The tumor, which was located in the body and tail of the
      pancreas, was successfully resected and the spleen was preserved. The outcome of
      surgery combined with the postoperative pathological examination resulted in the
      patient being misdiagnosed with a SPTP. During the consequent six-year follow-up
      period, low-density liver lesions and an intractable peptic ulcer gradually
      appeared. Finally, the patient diagnosis was confirmed as a malignant pancreatic
      neuroendocrine carcinoma with liver metastases. On June 1, 2011, a liver
      transplant was successfully performed and the patient has maintained a good
      overall condition. The underlying clinical and pathological factors that may have
      resulted in misdiagnosis are investigated in the present study. Through providing
      our preliminary clinical experiences and lessons, the aim of the present study
      was to focus the attention of clinicians on this type of cancer in order to
      improve its diagnosis and treatment.

PMID- 24932295
TI  - Resveratrol inhibits the phosphatidylinositide 3-kinase/protein kinase
      B/mammalian target of rapamycin signaling pathway in the human chronic myeloid
      leukemia K562 cell line.
AB  - Resveratrol inhibits the initiation, promotion and progression of tumors,
      however, the mechanism by which resveratrol inhibits the proliferation of the
      human chronic myeloid leukemia K562 cell line remains unclear. The present study
      was conducted to investigate the effect of resveratrol on the activation of the
      phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of
      rapamycin (mTOR) signaling cascade in K562 cells. Resveratrol showed significant
      cytotoxic effects and induced apoptosis in K562 cells in a dose- and time
      dependent manner. In addition, resveratrol attenuated the phosphorylation of
      PI3K, Akt and mTOR in the K562 cells. Furthermore, the selected inhibitors of
      PI3K (LY294002), Akt (SH-6) and mTOR (rapamycin) enhanced the effects of
      resveratrol in K562 cells. In addition, cyclin D1 levels were found to decrease
      and the activation of caspase-3 was observed. Resveratrol was also found to
      significantly attenuate the phosphorylation of the downstream molecules, p70S6K
      and 4EBP1. These results suggested that the downregulation of the PI3K/Akt/mTOR
      signaling cascades may be a crucial mediator in the inhibition of proliferation
      and induction of apoptosis by resveratrol in K562 cells.

PMID- 24932296
TI  - Tongue squamous cell carcinoma as a possible distinct entity in patients under 40
      years old.
AB  - Much controversy exists in the published literature regarding the clinical course
      and prognosis of tongue squamous cell carcinoma (SCC) in young patients. The aim
      of the current study was to evaluate the clinical results of tongue SCC in young
      patients. A total of 176 patients were included in this retrospective study. The
      patients were divided into two groups (young and old) according to an age cut-off
      of 40 years. The chi2 test and Kaplan-Meier method were used to analyze the
      variables. In total, 15 patients were <40 years old and placed into the young
      group, with five-year recurrence-free survival (RFS) and disease-specific
      survival (DSS) rates of 30 and 63%, respectively, compared with 47 and 62%,
      respectively, in the old group. No significant differences were identified
      between the RFS and DSS rates of the two groups, however, the young patients
      exhibited a different failure pattern. Overall, nine out of 10 recurrences in the
      young group occurred at a primary site compared with 18 out of 70 in the old
      group (P<0.001). Univariate analysis revealed that gender and differentiation
      were associated with recurrence and neck nodal involvement. In addition, poor
      differentiation was found to significantly decrease the DSS time. However, the
      prognosis of tongue SCC in the young patient group did not appear to differ from
      that of the old patient group. Furthermore, in the young patient group, local
      recurrence was the most common failure pattern and tumor differentiation was the
      most important prognostic factor.

PMID- 24932297
TI  - Expression profiling of stem cell signaling alters with spheroid formation in
      CD133high/CD44high prostate cancer stem cells.
AB  - Cancer stem cells (CSC) isolated from multiple tumor types differentiate in vivo
      and in vitro when cultured in serum; however, the factors responsible for their
      differentiation have not yet been identified. The first aim of the present study
      was to identify CD133high/CD44high DU145 prostate CSCs and compare their profiles
      with non-CSCs as bulk counterparts of the population. Subsequently, the two
      populations continued to be three-dimensional multicellular spheroids.
      Differentiation was then investigated with stem cell-related genomic
      characteristics. Polymerase chain reaction array analyses of cell cycle
      regulation, embryonic and mesenchymal cell lineage-related markers, and
      telomerase reverse transcriptase (TERT) and Notch signaling were performed.
      Immunohistochemistry of CD117, Notch1, Jagged1, Delta1, Sox2, c-Myc, Oct4, KLF4,
      CD90 and SSEA1 were determined in CSC and non-CSC monolayer and spheroid
      subcultures. Significant gene alterations were observed in the CD133high/CD44high
      population when cultured as a monolayer and continued as spheroid. In this group,
      marked gene upregulation was determined in collagen type 9 alpha1, Islet1 and
      cyclin D2. Jagged1, Delta-like 3 and Notch1 were respectively upregulated genes
      in the Notch signaling pathway. According to immunoreactivity, the staining
      density of Jagged1, Sox2, Oct4 and Klf-4 increased significantly in CSC
      spheroids. Isolated CSCs alter their cellular characterization over the course of
      time and exhibit a differentiation profile while maintaining their former surface
      antigens at a level of transcription or translation. The current study suggested
      that this differentiation process may be a mechanism responsible for the
      malignant process and tumor growth.

PMID- 24932298
TI  - Detection of circulating tumor cells in the cerebrospinal fluid of a patient with
      a solitary metastasis from breast cancer: A case report.
AB  - Brain lesions identified following the diagnosis and eradication of primary
      cancers are often ambiguous in origin, existing as a solitary metastasis or an
      independent primary brain tumor. The brain is a relatively common site of
      metastasis with breast cancer, although determining whether metastases have
      originated from the breast or brain is often not possible without invasive
      biopsies. In the current case report, a patient presented with a brain lesion
      identified by radiography and was without systemic disease. The patient had
      previously exhibited a complete response to chemotherapy and surgery for a poorly
      differentiated invasive ductal carcinoma. The origin of the brain lesion could
      not be determined by magnetic resonance imaging, giving rise to a diagnostic
      dilemma with diverging treatment options. We previously reported a method to
      isolate and enumerate tumor cells of epithelial origin in the cerebrospinal fluid
      (CSF). CSF tumor cell analysis of the patient revealed massive CSF tumor cell
      burden of epithelial origin, indicating that the brain lesion was likely of
      breast origin. The current case report highlights the use of CSF tumor cell
      detection as a differential diagnostic tool, in addition to its previously
      demonstrated use as a marker of disease burden and therapeutic response.

PMID- 24932299
TI  - TGFalpha-PE38 enhances cytotoxic T-lymphocyte killing of breast cancer cells.
AB  - The aim of the present study was to determine whether the combination of two
      modalities of immunotherapy, targeting two different tumor antigens, may be
      feasible and non-toxic, yet enhance the killing of a human breast cancer cell
      line. The first modality was tumor growth factor alpha-Pseudomonas exotoxin 38
      (TGFalpha-PE38), which specifically targets and kills tumor cells that express
      the epidermal growth factor receptor. The second modality was mucin-1 (MUC1)
      specific cytotoxic T lymphocytes (CTLs), generated by MUC1 stimulation of
      peripheral blood mononuclear cells, to target the human breast cancer cell line,
      MCF7. TGFalpha-PE38 exhibited specific lysis of the MCF7 cells in a concentration
      and time-dependent manner. TGFalpha-PE38 did not kill the normal hematopoietic
      stem cells or CTLs. Furthermore, TGFalpha-PE38 was not inhibitory for the growth
      or differentiation of the normal human hematopoietic stem cells into erythroid
      and myeloid colonies. In addition, TGFalpha-PE38 did not inhibit the killing
      function of CTLs, either when preincubated or co-incubated with CTLs. Finally,
      therapeutic enhancement was observed, in that TGFalpha-PE38 and CTLs were
      additive in the specific lysis of the MCF7 cells. These two modalities of
      immunotherapy may be beneficial for humans with breast cancer with or without
      other therapies, including autologous hematopoietic stem cell transplantation,
      specifically for purging cancer cells from hematopoietic stem cells prior to
      transplantation.

PMID- 24932300
TI  - Embolization of renal artery pseudoaneurysm following laparoscopic partial
      nephrectomy for central renal tumor: A report of two cases.
AB  - Laparoscopic partial nephrectomy has recently emerged as a minimally invasive
      treatment for small- to moderate-sized renal tumors. Renal artery pseudoaneurysms
      (RAPs) have been well-reported in patients with renal trauma or who have
      undergone percutaneous urological procedures, including biopsy, nephrostomy and
      percutaneous nephroureterolithotomy. However, RAP following laparoscopic partial
      nephrectomy for central renal tumor is a rare but serious, potentially life
      threatening complication. In total, two patients underwent laparoscopic partial
      nephrectomy at The First Affiliated Hospital of Zhejiang University School of
      Medicine (Hangzhou, China) for central renal tumors that had developed gross
      hematuria several weeks following the surgical procedures. The formation of RAPs
      was confirmed by contrast-enhanced computed tomography scans. Superselective
      embolizations of the renal artery branches were successfully performed to treat
      these two patients. In the current report, the etiology, diagnosis and management
      of RAPs are discussed.

PMID- 24932301
TI  - Plasma vascular endothelial growth factor 165 in advanced non-small cell lung
      cancer.
AB  - Currently, there is no serum marker that is routinely recommended for lung
      cancer. Therefore, the aim of the present study was to demonstrate that plasma
      vascular endothelial growth factor 165 (VEGF 165) may be a potential marker for
      advanced lung cancer. Lung cancer is the leading cause of cancer-related
      mortality worldwide, therefore, it is important to develop novel diagnostic
      techniques. The present prospective case control study included two groups of
      patients; a control group of healthy volunteers and a second group of patients
      with advanced non-small cell lung cancer (NSCLC). The plasma VEGF 165 levels were
      measured at baseline by ELISA prior to the first-line gemcitabine-cisplatin
      regimen. The high VEGF 165 expression level cut-off was >703 pg/ml, and the
      primary endpoint was used to compare the plasma VEGF 165 levels between the NSCLC
      patients and the control group subjects. The secondary endpoint was used to
      identify the correlations between high VEGF 165 levels and; clinical response
      (CR), progression-free survival (PFS) and overall survival (OS) in the advanced
      NSCLC patients. In total, patients with advanced NSCLC (n=35) were compared with
      a control group of age- and gender-matched healthy subjects (n=34). The follow-up
      period was between Oct 2009 and Oct 2012, with a median follow-up time of 10.5
      months. The median plasma VEGF 165 level was 707 pg/ml in the NSCLC patients
      versus 48 pg/ml in the healthy control subjects (P<0.001). However, no
      significant correlation was found between the plasma VEGF 165 levels and CR
      (P<0.5), median PFS (P=1.00) or OS (P=0.70). Therefore, it was concluded that
      plasma VEGF 165 may serve as a potential diagnostic marker for advanced NSCLC.

PMID- 24932302
TI  - Usefulness of short-term eltrombopag treatment as a supportive treatment in
      hepatocellular carcinoma patients with cirrhosis and severe thrombocytopenia: A
      report of two cases.
AB  - Eltrombopag is an oral thrombopoietin (TPO) receptor agonist that increases
      platelet counts in patients with idiopathic thrombocytopenic purpura and in
      patients with liver cirrhosis. When cirrhotic patients with thrombocytopenia
      undergo elective invasive procedures, eltrombopag treatment reduces the
      requirement for platelet transfusions. However, TPO is known to have
      proliferative effects on hepatic progenitor cells and hepatic sinusoidal
      endothelial cells, which indicates that eltrombopag may accelerate tumor
      progression. Thus, the effect of eltrombopag on hepatocellular carcinoma (HCC)
      progression is an important issue. The current study describes two cases of HCC
      with cirrhosis-related thrombocytopenia. A two-week administration of eltrombopag
      increased platelet counts from 4.8 to 11.3*104 /MUl in case 1 and 4.5 to 23.2*104
      /MUl in case 2. However, no changes were identified in the serum levels of tumor
      markers or HCC size following eltrombopag administration in the two cases. These
      HCCs were curatively treated by radiofrequency ablation without platelet
      transfusions or serious bleeding. Thus, short-term eltrombopag administration may
      not accelerate HCC proliferation and may be beneficial for invasive HCC treatment
      in cirrhotic patients with thrombocytopenia.

PMID- 24932303
TI  - The role of MALAT1 correlates with HPV in cervical cancer.
AB  - Cervical cancer, the second most common type of cancer in women worldwide, is
      responsible for >275,100 mortalities each year and is associated with high-risk
      human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7,
      which have crucial roles in malignant transformation in cervical cancer.
      Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non
      coding RNA originally identified in non-small cell lung cancer. Previous studies
      have revealed that MALAT1 is expressed in numerous tissue types, and is
      significant in maintaining the normal function of the body. However, it also
      appeared to be notably upregulated in numerous carcinoma types compared with
      adjacent non-cancerous tissues. In the present study, it was identified that
      MALAT1 expression was upregulated in cervical cancer cell lines compared with
      normal cervical squamous cell samples. Further study into the effect of MALAT1 on
      cellular phenotype revealed that MALAT1 was able to promote cell migration and
      proliferation. Of note, it was revealed that the expression of MALAT1 was
      decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the
      investigations in clinical samples also revealed that MALAT1 was expressed in HPV
      positive cervical squamous cells, but not in HPV-negative normal cervical
      squamous cells. These results indicate that HPV correlates with MALAT1
      deregulation in cervical cancer.

PMID- 24932304
TI  - Enhanced antitumor effects of low-frequency ultrasound and microbubbles in
      combination with simvastatin by downregulating caveolin-1 in prostatic DU145
      cells.
AB  - Advanced prostate cancer is difficult to treat due to androgen resistance, its
      deep location and blood tumor barriers. Low-frequency ultrasound (LFU) has
      potential clinical applications in the treatment of prostate cancer due to its
      strong penetrability and high sensitivity towards tumor cells. Simvastatin has
      often been administered as a preventive agent in prostate tumors. The aim of the
      present study was to investigate the enhanced effects of LFU and microbubbles in
      combination with simvastatin, in inhibiting cell viability and promoting
      apoptosis of androgen-independent prostatic DU145 cells. Cultured DU145 cells
      were divided into six groups based on the combination of treatments as follows:
      Control, LFU, LFU and microbubbles (LFUM), simvastatin, LFU and simvastatin, LFUM
      and simvastatin. The cells were treated by LFU (80 kHz) continuously for 30 sec
      with an ultrasound intensity of 0.45 W/cm2 and a microbubble density of 20%.
      Simvastatin was added 30 h prior to the ultrasound exposure. The results
      indicated that cell viability was marginally reduced in the LFU and simvastatin
      alone treatment groups compared with the control 24 h following ultrasound
      exposure. The combination of LFU, with microbubbles or simvastatin, potentiated
      the growth inhibition; the greatest inhibition was observed in the cells that
      were subject to treatment with LFUM and simvastatin in combination. Furthermore,
      this inhibitory effect was enhanced in a time-dependent manner. For cell
      apoptosis, a low dose of simvastatin had no apparent affect on the DU145 cells,
      while LFU marginally promoted cell apoptosis. Microbubbles or simvastatin
      increased the apoptosis rate of the DU145 cells, however, the combination of LFUM
      and simvastatin induced a strong synergistic effect on cell apoptosis. Western
      blotting analysis demonstrated a high expression level of caveolin-1 in resting
      DU145 cells. LFUM or combined LFU and simvastatin resulted in a greater reduction
      in the expression compared with the control group (P<0.05). The expression of
      caveolin-1 was lowest in the LFUM combined with simvastatin treatment group. The
      expression of phospho-Akt (p-Akt) was consistent with caveolin-1, with the lowest
      expression levels of p-Akt observed in the cells that were treated with the
      combination of LFUM and simvastatin. The results indicate that LFUM in
      combination with simvastatin may additively or synergistically inhibit cell
      viability and induce apoptosis of DU145 cells by downregulating caveolin-1 and p
      Akt protein expression.

PMID- 24932305
TI  - Capillary morphogenesis gene 2 regulates adhesion and invasiveness of prostate
      cancer cells.
AB  - Capillary morphogenesis gene 2 (CMG2), also known as anthrax toxin receptor 2,
      has been indicated in the formation of new vasculature and in the internalisation
      of the anthrax toxin. Anti-angiogenesis therapy that targets this molecule has
      been investigated. However, our recent studies of this molecule have indicated
      that this gene may also play certain roles in cancer cells. The present study
      aimed to examine the expression of CMG2 in prostate cancer tissues and cell
      lines, and also its impact on cellular functions. The expression of CMG2 was
      detectable in normal and prostate cancer tissues. The prostate cancer cell lines
      appeared to have relatively high expression compared with the prostatic
      epithelial cells. Knockdown of CMG2 impaired the adherence of the prostate cancer
      cells. CMG2 overexpression resulted in decreasing invasiveness, while the
      knockdown of CMG2 contrastingly enhanced this ability. The altered expression of
      CMG2 in the prostate cancer cells did not affect the in vitro or in vivo growth
      of the cells. Taken together, these results show that CMG2 is expressed in
      prostatic epithelia and cancer cells. In addition to its role in the angiogenesis
      and the internalisation of anthrax toxin, CMG2 also plays an important role in
      regulating the adhesion and invasion of prostate cancer cells.

PMID- 24932306
TI  - Supraglottic adenoid cystic carcinoma mimicking laryngeal amyloidosis: A case
      report.
AB  - Supraglottic adenoid cystic carcinoma (ACC) is extremely rare and may be
      misdiagnosed as laryngeal amyloidosis. The present report describes a case of
      supraglottic ACC, which went unrecognized until histopathological examination of
      the neoplasm 18 months after the first presentation. The present patient
      presented with progressive hoarseness for half a year and initially required
      partial resection. Following quick regional recurrence, the patient received a
      total laryngectomy while refusing radiotherapy. Adjuvant post-operational
      traditional Chinese medicine was accepted. Over 3 years' follow-up, there was no
      evidence of regional relapse or distant metastases. The present case is compared
      with a second case of supraglottic submucosal mass in which the signs, symptoms
      and examinations were similar to the first case, but that was diagnosed as
      laryngeal amyloidosis. Attention should be paid to submucosal masses in the
      larynx to prevent underlying malignancy and subsequent disease progression.
      Immunocytochemistry, such as p63 staining, is mandatory for making an early
      differential diagnosis of supraglottic ACC. Traditional Chinese medicine may be a
      useful adjuvant therapy for this rare disease.

PMID- 24932307
TI  - Diagnosis and treatment of retroperitoneal bronchogenic cysts: A case report.
AB  - Bronchogenic cysts are uncommon, predominantly benign, congenital malformations
      arising from the primitive foregut. The occurrence of such cysts in the
      retroperitoneum is extremely rare. The present study presents the case of a 30
      year-old female who presented with a left adrenal mass. Imaging investigations
      revealed a cystic mass located medially to the left adrenal gland.
      Retroperitoneal laparoscopic excision and complete resection were performed, and
      the subsequent pathological examination confirmed the diagnosis of a bronchogenic
      cyst in the retroperitoneum. The patient was discharged on the fourth post
      operative day and received no further treatment, however, regular follow-up was
      performed due to the lesion being benign. A rare case of bronchogenic cyst and
      literature review is presented, which may aid in improving the understanding of
      the etiology and pathogenesis of retroperitoneum bronchogenic cysts.

PMID- 24932308
TI  - Gastric cancer cell growth and epithelial-mesenchymal transition are inhibited by
      gamma-secretase inhibitor DAPT.
AB  - The Notch signaling pathway may be important in the development and progression
      of several malignancies. However, the functions of Notch signaling in epithelial
      mesenchymal transition (EMT) remain largely unknown. The aim of the present study
      was to delineate Notch1 expression in gastric cancer (GC) and its function in GC
      EMT. Using quantitative polymerase chain reaction and western blot analysis, the
      expression of Notch1 was found to increase in GC cell lines compared with the
      normal gastric mucosa cell line. In addition, Notch1 expression was found to be
      downregulated in the non-metastatic-derived GC cell line compared with the
      metastatic-derived cell line. Furthermore, Notch1 expression was significantly
      increased in the tumor tissues compared with the adjacent normal mucosa tissues,
      as well as in patients with metastases than in patients without metastases. To
      explore the role of the Notch1 signaling pathway in EMT, the GC cell lines, AGS
      and MKN45, were treated with gamma-secretase inhibitor DAPT. Using MTT, Transwell
      and clonality assays, DAPT was found to inhibit the expression of the Notch1
      downstream target, Hes1, and impair the ability of the GC cell lines to migrate,
      invade and proliferate. The protein levels of the mesenchymal markers, vimentin,
      neural cadherin and Snail, were decreased; however, the expression of the
      epithelial marker, epithelial cadherin, was increased in the GC cell lines
      treated with DAPT. These results indicated that the Notch1 signaling pathway may
      be important in the development and progression of GC. In conclusion, DAPT
      inhibits the Notch1 signaling pathway, as well as the growth, invasion,
      metastasis and EMT of GC cells.

PMID- 24932309
TI  - Involvement of ephrin receptor A4 in pancreatic cancer cell motility and
      invasion.
AB  - Ephrin (EPH) receptors can be classified into EPHA and EPHB receptors and are
      important in diverse cellular processes. EPHA4, a member of the EPHA receptors,
      has been demonstrated to be elevated in various human cancers and involved in the
      tumor progression. However, the role of EPHA4 in pancreatic cancer cells remains
      unclear. Therefore, the present study transfected Panc-1 and BxPC-3 cells with
      small interfering RNA (siRNA) to knockdown the expression of EPHA4. Wound healing
      and invasion assays were then performed to assess the effect of EPHA4 knockdown
      on the motility and invasion of pancreatic cancer cells. The results demonstrated
      that the knockdown of EPHA4 by siRNA inhibits the motility and invasion of
      pancreatic cancer cells. Furthermore, gelatin zymography assay showed that EPHA4
      may regulate the activity of matrix metalloproteinase (MMP)-2. In addition, the
      knockdown of EPHA4 increased the expression of epithelial (E)-cadherin, as well
      as decreased the expression of Snail. Overall, these results suggested that EPHA4
      may promote the motility and invasion of pancreatic cancer cells via the
      upregulation of MMP-2 and Snail, as well as the downregulation of E-cadherin.
      Thus, EPHA4 may act as a useful target for the treatment of pancreatic cancer.

PMID- 24932310
TI  - Epithelioid angiosarcoma of the spine: A case report of a rare bone tumor.
AB  - Epithelioid angiosarcoma (EA) is an extremely rare subtype of angiosarcoma, which
      is characterized by large cells with an epithelioid morphology. EA typically
      arises in deep soft tissues, including the adrenal gland, skin and thyroid,
      however, EA rarely arises in the spine. The current study presents a case of
      osteolytic lesions involving the fourth lumbar (L4) level of the spine.
      Preoperatively, the patient was misdiagnosed with metastatic carcinoma, however,
      a radiological examination detected the presence of osteolytic or destructive
      lesions in the vertebrae, which extended into the pedicles. Histopathological and
      immunohistochemical evaluations were performed on the tumor tissue obtained from
      a decompression specimen of the L4 vertebra. A bone lesion composed of sheet-like
      malignant cells exhibiting atypical epithelioid morphology with vascular
      formation was observed. The presence of anastomosing vascular channels lined by
      epithelioid endothelial cells also indicated that focal endothelial
      differentiation had occurred. In addition, immunohistochemistry assays revealed
      that the lesion was positive for the endothelial cell markers, CD31, CD34 and
      vimentin. The tumor was treated with decompression of the L4 vertebra, followed
      by posterior stabilization. The patient subsequently refused chemotherapy and
      radiotherapy but completed six months of follow-up. At the time of writing, the
      tumor remains under control and the patient is asymptomatic. This case highlights
      the difficulty of diagnosing EA, which requires careful pathological examination
      and immunophenotype labeling. At present, CD31 is the most sensitive marker for
      detecting EA.

PMID- 24932311
TI  - Increased phosphatidylethanolamine N-methyltransferase gene expression in non
      small-cell lung cancer tissue predicts shorter patient survival.
AB  - Lipid mobilization is of great importance for tumor growth and studies have
      suggested that cancer cells exhibit abnormal choline phospholipid metabolism. In
      the present study, we hypothesized that phosphatidylethanolamine N
      methyltransferase (PEMT) gene expression is increased in non-small-cell lung
      cancer (NSCLC) tissues and that increased gene expression acts as a predictor of
      shorter patient survival. Forty-two consecutive patients with resected NSCLC were
      enrolled in this study. Paired samples of lung cancer tissues and adjacent non
      cancer lung tissues were collected from resected specimens for the estimation of
      PEMT expression. SYBR Green-based real-time polymerase chain reaction was used
      for quantification of PEMT mRNA in lung cancer tissues. Lipoprotein lipase (LPL)
      and fatty acid synthase (FASN) activities had already been measured in the same
      tissues. During a four-year follow-up, 21 patients succumbed to tumor
      progression. One patient did not survive due to non-cancer reasons and was not
      included in the analysis. Cox regression analysis was used to assess the
      prognostic value of PEMT expression. Our findings show that elevated PEMT
      expression in the cancer tissue, relative to that in the adjacent non-cancer lung
      tissue, predicts shorter patient survival independently of standard prognostic
      factors and also independently of increased LPL or FASN activity, the two other
      lipid-related predictors of shorter patient survival. These findings suggest that
      active phosphatidylcholine and/or choline metabolism are essential for tumor
      growth and progression.

PMID- 24932312
TI  - Circulating free mitochondrial DNA concentration and its association with
      erlotinib treatment in patients with adenocarcinoma of the lung.
AB  - Changes in circulating free DNA concentrations have been correlated with
      chemotherapeutic effects in solid tumors. The present study was designed to
      determine and compare the changes in circulating free mitochondrial DNA (mtDNA)
      concentrations prior to and following erlotinib treatment, as well as the
      potential prognostic value of plasma mtDNA. Patients with adenocarcinoma of the
      lung who were to receive erlotinib treatment were enrolled in the present study
      once informed consent had been obtained. Patient plasma samples were collected
      immediately prior to starting erlotinib treatment, on days 15 and 29 following
      the initiation of erlotinib treatment and also when the patient's disease had
      progressed. The most common erlotinib treatment response was a partial response
      (PR), achieved in 26 (49.1%) of the 53 enrolled patients, followed by stable
      disease (SD) in 13 patients (24.5%) and progressive disease (PD) in 14 patients
      (26.4%). Plasma mtDNA concentrations were significantly decreased on day 15
      compared with day 0 in the patients with PD (P=0.028) or in those patients
      without a response to erlotinib treatment (SD and PD; P=0.007). Plasma mtDNA
      concentrations were similar or elevated on day 15 compared with day 0 in the
      patients with a PR (P=0.808). The concentration of plasma mtDNA did not correlate
      with progression-free survival (PFS). Tumor epidermal growth factor receptor
      (EGFR) mutation status (activating mutations in 16 patients and wild-type in 14
      patients) did not correlate with the concentration of plasma mtDNA (P=0.951).
      Plasma mtDNA levels did not correlate with the PFS of the patients when they
      received erlotinib treatment. The plasma mtDNA levels were decreased on day 15 in
      those patients who had disease progression following erlotinib treatment. These
      results demonstrate that plasma mtDNA is of weak clinical utility as a screening,
      diagnostic or prognostic tool in lung cancer patients.

PMID- 24932313
TI  - FBXL20 acts as an invasion inducer and mediates E-cadherin in colorectal
      adenocarcinoma.
AB  - The mechanisms eliciting colorectal adenocarcinoma are not well understood and
      the FBXL20 gene is problematic as it exhibits an abnormal expression in
      colorectal cancer cells. In the present study a recombinant plasmid, pReceiver
      M03-FBL20 expression plasmid was constructed, which overexpressed FBXL20; this
      was transfected into Lovo cells to form Lovo-FBL20 cells. The FBXL20 expression
      level was examined by quantitative polymerase chain reaction (qPCR) and western
      blot analysis. The cell viability and invasion capacity were measured using cell
      counting kit 8, Transwell chamber and wound healing assays, respectively. The
      associated genes, including E-cadherin, beta-catenin, c-Myc, SET nuclear
      oncogene, protein phosphatase-2A, Axin, p53 and caspase 3, were detected by qPCR
      and western blotting. It was demonstrated that the FBXL20 expression level was
      markedly upregulated in the Lovo-FBL20 cells transfected with pReceiver-M03-FBL20
      expression plasmid, compared with that of the Lovo cells. In addition, the cell
      viability and invasion capacity of the Lovo-FBL20 cells were significantly
      increased. These increases correlated with a significant upregulation in the
      expression level of beta-catenin and c-Myc, and a downregulated expression level
      of E-cadherin. The results of the present study indicate that FBXL20 may mediate
      the ubiquitin degradation of E-cadherin resulting in an increased invasive
      ability of malignant cells.

PMID- 24932315
TI  - Erratum: Clinical significance of the induction of macrophage differentiation by
      the costimulatory molecule B7-H3 in human non-small cell lung cancer.
AB  - [This corrects the article on p. 1253 in vol. 6, PMID: 24179504.].

PMID- 24932314
TI  - A rapid nested polymerase chain reaction method to detect circulating cancer
      cells in breast cancer patients using multiple marker genes.
AB  - The aim of the present study was to develop a simple and rapid method for the
      detection of circulating cancer cells using multiple tumor markers and to
      investigate the clinical significance of circulating cancer cells in breast
      cancer patients. A novel rapid nested polymerase chain reaction (PCR) assay, with
      high sensitivity and specificity, was evaluated, which was considered to be
      suitable for clinical application. The rapid nested PCR method was used to detect
      the circulating cancer cells of 142 breast cancer patients, using a panel of
      marker genes (FAM83A, NPY1R and KRT19), which were identified by the Digital Gene
      Expression Displayer Tool of the National Cancer Institute-Cancer Genome Anatomy
      Project. In total, 79.6% of the 142 breast cancer patient blood samples were
      found to express at least one tumor marker. In addition, the number of positive
      markers was found to significantly correlate with the disease stage and presence
      of distant metastasis. Furthermore, positivity for more than one tumor marker
      appeared to predict a reduced survival time in breast cancer patients.

PMID- 24932317
TI  - Mouse IPK: A Powerful Tool to Partially Characterize Renal Reperfusion and
      Preservation Injury.
AB  - MAIN PROBLEM: The molecular basis of renal preservation injury is not well
      understood. Since mouse kidney transplantation models are not useful in this
      setting, a mouse Isolated Perfused Kidney (IPK) model was developed to take
      advantage of mouse genetic design capabilities for testing complex biological
      hypothesis regarding mechanisms of preservation injury in transplanted kidneys.
      METHODS: Mouse kidneys were recovered, preserved, and reperfused in-vitro with an
      acellular physiological crystalloid buffer containing hypo-physiological oncotic
      pressure. Outcome variables were measured to predict preservation injury. These
      included perfusate flow, vascular resistance, VO2, urine output, GFR,
      proteinuria, LDH release, and edema. The model was tested by subjecting mouse
      kidneys to cold storage in University of Wisconsin (UW) solution for 24, 48, or
      72 hours (time-dependent preservation injury), cold storage in Euro-Collins
      Solution (solution dependent preservation injury), and exposure to prior warm
      ischemia (DCD dependent preservation injury). RESULTS: The model accurately
      predicted the qualitative and quantitative changes in the readouts based on known
      responses to preservation injury in kidney transplants in large animals and
      humans. CONCLUSION: The mouse IPK accurately predicts many of the variables
      associated with renal organ preservation injury in the very early phases of
      reperfusion and may provide an attractive model for studying the molecular basis
      of renal preservation injury.

PMID- 24932316
TI  - Imaging Biomarkers for Intra-arterial Stroke Therapy.
AB  - Despite high rates of early revascularization with intra-arterial stroke therapy,
      the clinical efficacy of this approach has not been clearly demonstrated.
      Neuroimaging biomarkers will be useful in future trials for patient selection and
      for outcomes evaluation. To identify patients who are likely to benefit from
      intra-arterial therapy, the combination of vessel imaging, infarct size
      quantification and degree of neurologic deficit appears critical. Perfusion
      imaging may be useful in specific circumstances, but requires further validation.
      For measuring treatment outcomes, surrogate biomarkers that appear suitable are
      angiographic reperfusion as measured by the modified Thrombolysis in Cerebral
      Infarction scale and final infarct volume.

PMID- 24932318
TI  - Cell-induced flow-focusing instability in gelatin methacrylate microdroplet
      generation.
AB  - Photo-crosslinkable gelatin methacrylate (GelMa) microspheres are applicable to
      deliver cells or drugs in biological or biomedical applications. To fabricate
      GelMa microdroplets, a flow focusing technique with advantages of size control
      and rapid production was used in a T-junction microfluidic device. Instability
      played an important role in promoting microdroplet uniformity. 5 wt. % GelMa
      prepolymer solution mixed with cells affected cell-induced instability. At low
      flow rate ratio of GelMa to mineral oil below 0.200, stability was maintained
      regardless of GelMa concentration (5 and 8 wt. %) and cell presence, which led to
      uniform microdroplet generation. In contrast, instability at high flow rate ratio
      above 0.200 was worsened by cell presence and unstable jetting length, resulting
      in the generation of non-uniform cell-laden microdroplets. Therefore, the effect
      of cell-induced instability on microdroplet generation was minimized at a low
      flow rate ratio. 

PMID- 24932319
TI  - Influence of Structural Heterogeneity on Diffusion of CH4 and CO2 in Silicon
      Carbide-Derived Nanoporous Carbon.
AB  - We investigate the influence of structural heterogeneity on the transport
      properties of simple gases in a Hybrid Reverse Monte Carlo (HRMC) constructed
      model of silicon carbide-derived carbon (SiC-DC). The energy landscape of the
      system is determined based on free energy analysis of the atomistic model. The
      overall energy barriers of the system for different gases are computed along with
      important properties, such as Henry constant and differential enthalpy of
      adsorption at infinite dilution, and indicate hydrophobicity of the SiC-DC
      structure and its affinity for CO2 and CH4 adsorption. We also study the effect
      of molecular geometry, pore structure and energy heterogeneity considering
      different hopping scenarios for diffusion of CO2 and CH4 through ultramicropores
      using the Nudged Elastic Band (NEB) method. It is shown that the energy barrier
      of a hopping molecule is very sensitive to the shape of the pore entry. We
      provide evidence for the influence of structural heterogeneity on self
      diffusivity of methane and carbon dioxide using molecular dynamics simulation,
      based on a maximum in the variation of self-diffusivity with loading. A
      comparison of the MD simulation results with self-diffusivities from quasi
      elastic neutron scattering (QENS) measurements and, with macroscopic uptake-based
      low-density transport coefficients, reveals the existence of internal barriers
      not captured in MD simulation and QENS experiments. Nevertheless, the simulation
      and macroscopic uptake-based diffusion coefficients agree within a factor of 2-3,
      indicating that our HRMC model structure captures most of the important energy
      barriers affecting the transport of CH4 in the nanostructure of SiC-DC.

PMID- 24932320
TI  - Analysis for stress environment in the alveolar sac model.
AB  - Better understanding of alveolar mechanics is very important in order to avoid
      lung injuries for patients undergoing mechanical ventilation for treatment of
      respiratory problems. The objective of this study was to investigate the alveolar
      mechanics for two different alveolar sac models, one based on actual geometry and
      the other an idealized spherical geometry using coupled fluid-solid computational
      analysis. Both the models were analyzed through coupled fluid-solid analysis to
      estimate the parameters such as pressures/velocities and displacements/stresses
      under mechanical ventilation conditions. The results obtained from the fluid
      analysis indicate that both the alveolar geometries give similar results for
      pressures and velocities. However, the results obtained from coupled fluid-solid
      analysis indicate that the actual alveolar geometry results in smaller
      displacements in comparison to a spherical alveolar model. This trend is also
      true for stress/strain between the two models. The results presented indicate
      that alveolar geometry greatly affects the pressure/velocities as well as
      displacements and stresses/strains.

PMID- 24932321
TI  - [Bilateral stress fracture of the legs following sustained walk].

PMID- 24932322
TI  - [Epidemiological, prognostic and therapeutic aspects of retro placental hematoma
      (HRP) in a referral maternity in rural area].

PMID- 24932323
TI  - [An immunoproliferative disease of the small intestine revealed by acute
      intussusception: report of a case].

PMID- 24932324
TI  - [Angioid streaks].

PMID- 24932326
TI  - Gastrocolic fistula secondary to primary gastric lymphoma.

PMID- 24932325
TI  - Stroke in Saudi Arabia: a review of the recent literature.
AB  - Stroke is a major cerebrovascular disease resulting in high mortality and
      persistent disability in adults across the world. Besides coronary heart disease
      and cancer, stroke is the commonest cause of death in most industrialized
      countries. Survivors of stroke are often left with severe mental and physical
      disabilities, which create a major social and economic burden, ranking as the
      second most common cause of death worldwide and a major source of morbidity. The
      Kingdom of Saudi Arabia (KSA) is the largest country in the Middle East occupying
      approximately four-fifths of the Arabian Peninsula supporting a population of
      more than 28 million. Stroke is becoming a rapidly increasing problem and an
      important cause of illness and deaths in Saudi Arabia. However, compared with the
      developed countries, research regarding the incidence, prevalence and their socio
      demographic properties of stroke is still insufficient due to lack of appropriate
      studies being conducted in these specified areas. This review aims to discuss the
      range of the aspect of stroke in Saudi Arabia from the literature published. 

PMID- 24932327
TI  - [Methotrexate toxicity during acute leukemia lymphoblastic].

PMID- 24932328
TI  - [Classic Kaposi disease with involvement of the musculoskeletal system: a new
      case].

PMID- 24932329
TI  - [Appendicular mucocele secondary to a caecal tumor].

PMID- 24932330
TI  - [Epulis: about a case].

PMID- 24932331
TI  - [Evolution of postoperative sequelae of pulmonary tuberculosis in HIV
      seropositive].

PMID- 24932332
TI  - [The migration of a ventriculoperitoneal shunt catheter].

PMID- 24932333
TI  - [Nodular hepatic tuberculosis: unusual complication during Wilson's disease].

PMID- 24932334
TI  - [Rare cause of perforation of the nasal septum].

PMID- 24932335
TI  - [Paratesticular rhabdomyosarcoma in a 14-month old infant].

PMID- 24932336
TI  - [A rare liver tumor in children: focal nodular hyperplasia].

PMID- 24932337
TI  - Perceived barriers to the implementation of Isoniazid preventive therapy for
      people living with HIV in resource constrained settings: a qualitative study.
AB  - INTRODUCTION: Isoniazid preventive therapy (IPT) reduces the risk of active TB.
      IPT is a key public health intervention for the prevention of TB among people
      living with HIV and has been recommended as part of a comprehensive HIV and AIDS
      care strategy. However, its implementation has been very slow and has been
      impeded by several barriers. OBJECTIVE: The Objective of the study is to assess
      the perceived barriers to the implementation of Isoniazid preventive therapy for
      people living with HIV in resource constrained settings in Addis Ababa, Ethiopia
      in 2010. METHODS: A qualitative study using a semi-structured interviewed guide
      was used for the in-depth interview. A total of 12 key informants including ART
      Nurse, counselors and coordinators found in four hospitals were included in the
      interview. Each session of the in-depth interview was recorded via audio tape and
      detailed notes. The interview was transcribed verbatim. The data was analyzed
      manually. RESULTS: The findings revealed that poor patient adherence was a major
      factor; with the following issues cited as the reasons for poor adherence;
      forgetfulness; lack of understanding of condition and patient non- disclosure of
      HIV sero-status leading to insubstantial social support; underlying mental health
      issues resulting in missed or irregular patient appointments; weak
      patient/healthcare provider relationship due to limited quality interaction; lack
      of patient information, patient empowerment and proper counseling on IPT; and the
      deficient reinforcement by health officials and other stakeholders on the
      significance of IPT medication adherence as a critical for positive health
      outcomes. CONCLUSION: Uptake of the implementation of IPT is facing a challenge
      in resource limited settings. This recalled provision of training/capacity
      building and awareness creation mechanism for the health workers, facilitating
      disclosure and social support for the patients is recommended.

PMID- 24932338
TI  - [Breech vaginal delivery: a study of maternal and neonatal morbidity and
      mortality].

PMID- 24932340
TI  - Chest trauma revealed an ostium secundum atrial septal defect in adulthood.

PMID- 24932339
TI  - [Profile of breast and gynecological cancers in Yaounde--Cameroon].

PMID- 24932341
TI  - Honeybee sting of the sclera: occular features, treatment, outcome and presumed
      pathogenesis.
AB  - Ocular bee sting injury has caused several reactions in the eye but has rarely
      been reported among local African farmers, and Nigerians in particular. This case
      seeks to report the first ocular and external eye reactions following a honey bee
      sting of the eye through the sclera, highlighting the treatment and outcome. Oral
      interview, clinical examination and external photographs were used to obtain and
      document findings. Medical treatment was instituted as soon as subject presented.
      There was complete inflammatory resolution within a week, normal vision and no
      evidence of stinger migration after four weeks of follow up. The wound site
      healed with ciliary staphyloma. The role of physical properties, immunological
      and genetics interplay and the presumed pathogenesis is further discussed. Health
      education on early presentation and avoidance of harmful traditional eye
      medications should be promoted among the farming populations in our communities,
      in order to prevent blinding complications. 

PMID- 24932342
TI  - [The trichobezoar: a rare cause of abdominal mass].

PMID- 24932343
TI  - [Generalized lichen nitidus].

PMID- 24932344
TI  - [Symphysis disjunction after an obstructed viginal delivery: report of a case].

PMID- 24932346
TI  - [Atypical zoster in an immunocompromised patient].

PMID- 24932345
TI  - Mapping knowledge management resources of maternal, newborn and child health
      (MNCH) among people living in rural and urban settings of Ilorin, Nigeria.
AB  - INTRODUCTION: Lack of access to information and knowledge about mother and child
      health was identified as a major contributor to poor maternal and child health in
      Nigeria. The Partnership for Maternal, Newborn and Child Health (PMNCH) has
      recognized mapping the knowledge management of Maternal Newborn and Child Health
      (MNCH) as one of the major strategies to be deployed in improving the health of
      these vulnerable groups. The main aim of this study is to map the knowledge
      management resources of Maternal, Newborn and Child Health (MNCH) in rural and
      urban settings of Ilorin West LGA of Kwara state Nigeria. METHODS: It is a
      descriptive cross-sectional study with a comparative analysis of findings from
      urban and rural settings. Epi-mapping was used to carve out the LGA and map
      responses. The p-value of less than 0.05 was considered significant at 95%
      confidence level. RESULTS: The study showed that traditional leader was
      responsible for more than half of the traditional way of obtaining information by
      rural (66.7%) and urban (56.2%) respondents while documentation accounts for the
      main MNCH knowledge preservation for the rural (40.6%) and the urban (50%)
      dwellers. Traditional leaders (32.2%) and elders (46.7%) were the main people
      responsible for dissemination of knowledge in rural areas whereas elders (35.9%)
      and Parents (19.9%) were the main people responsible in urban areas. CONCLUSION:
      It was concluded that traditional and family institutions are important in the
      knowledge management of MNCH in both rural and urban settings of Nigeria.

PMID- 24932347
TI  - Dysphagia secondary to anterior cervical spine osteophytes.

PMID- 24932348
TI  - Stroke in young adults: about 128 cases.
AB  - Ischemic stroke is rare in young adults, but it is genuinely a serious situation
      giving the fact that it touch a very active part of our society. We report a
      series of 128 cases. The purpose is to analyze the risk factors, etiologies and
      outcomes of ischemic stroke in young adults in Marrakesh. Retrospective study
      performed at the Neurology department Mohammed VI universitary hospital in
      Marrakesh interesting 128 patients. The diagnosis of ischemic stroke was assessed
      through clinical and radiological confrontation. RESULTS: The age of our patients
      varied from 18 to 45 years old, 76 males and 52 females giving a male: female
      ratio of 1:46. Hypertension was the first risk factor involved with 63 (49.2%)
      cases, followed by smoking with 52 (40.6%) patients. The causes of ischemic
      stroke were characterized by the predominance of the cardio embolic origin with
      43 (33.5%) cases, the existence of 14 (11%) cases of syphilitic arthritis, and
      the 52 (40.6%) cases of unknown etiologies. The authors stress the difficulties
      faced on supporting ischemic stroke in southern Morocco in particular when
      concerned by the etiological finding and the rehabilitation after the acute phase
      of the stroke. Our study points out the high incidence of embolic heart disease
      in our context. The lack of neurologists, low coverage of the population and the
      underestimation by physicians are factors that can explain why ischemic stroke
      remain undiagnosed.

PMID- 24932349
TI  - [Umbilical metastasis of a rectal tumor: report of a case].

PMID- 24932350
TI  - [Torsion of uterine appendages during pregnancy: report of a case at Yaounde
      Central Hospital, Cameroon].

PMID- 24932351
TI  - Prevalence of hepatitis B virus in patients with diabetes mellitus: a comparative
      cross sectional study at Woldiya General Hospital, Ethiopia.
AB  - INTRODUCTION: The overall prevalence of HBV in Ethiopia varies from 4.7-16.8% for
      Hepatitis B surface antigen (HBsAg) and 70-76.38% for at least one marker
      positive. Patients suffering from type I Diabetes Mellitus (DM) incur high risk
      of infection with hepatotropic viruses because of frequent hospitalization and
      blood tests. METHODS: A comparative cross sectional study was conducted at
      Woldiya General Hospital using 108 consented study populations from Diabetes and
      108 non diabetes control groups during the period November 2010 - January 2011.
      VISITECT HBsAg rapid test kit and Humastat 80 chemistry analyzer were used.
      Multivariate logistic regression was used to see the association of HBV with
      clinical history of participants and Sociodemographic variables. All tests were
      two-sided with alpha-level of 0.05 and 80% power. RESULTS: Prevalence of HBsAg
      was equal between diabetic and non diabetic individuals, 3.7% indicating that
      there was no difference between the two groups. Only history of invasive
      procedures and chronic liver disease showed association with HBsAg
      seropositivity. CONCLUSION: In this study a positive relation was not indicated
      between HBV and Diabetes and the prevalence of HBsAg was equal between diabetic
      and non diabetic individuals.

PMID- 24932352
TI  - A Preliminary Examination of the Relationship Between the 5-HTTLPR and Childhood
      Emotional Abuse on Depressive Symptoms in 10-12-Year-Old Youth.
AB  - Childhood emotional abuse (CEA) is a pervasive problem associated with negative
      sequelae such as elevated depressive symptoms. Key stress-related genes, such as
      the 5-HTTLPR polymorphism, interact with childhood abuse to produce elevated
      depressive symptoms in older adolescent girls, but not in older adolescent boys.
      To date, studies have not examined this relationship as a function of CEA
      specifically or among younger adolescents. To extend prior work, we examined the
      effects of the 5-HTTLPR and CEA on depressive symptoms among 10-12-year-old
      youth. Based on previous findings, we expected a main effect of CEA on depressive
      symptoms among all youth, but only expected an interactive effect between the 5
      HTTLPR and CEA on depressive symptoms in girls. In the current study, 222 youth
      (mean age 11.02 years, 44.1% girls, 51.6% Caucasian, 33.0% African American, 2.7%
      Latino, and 12.7% other) and their parent(s)/guardian(s) completed the Revised
      Child Anxiety and Depression Scale and the Emotional Abuse subscale of the
      Childhood Trauma Questionnaire and provided saliva samples for genotyping the 5
      HTTLPR. Results indicate that CEA, but not the 5-HTTLPR, was related to elevated
      depressive symptoms among boys. Among girls, each copy of the s allele of the 5
      HTTLPR was related to increased depressive symptoms, but only for those who had
      experienced CEA. Our results extend prior findings by specifically examining CEA
      and by focusing on 10-12-year-old youth. These results, although preliminary,
      suggest that focusing on the interplay between putative genetic markers and a
      broader range of environmental events, such as CEA, might allow researchers to
      determine factors differentially influencing the later emergence of sex
      differences in depressive symptoms.

PMID- 24932354
TI  - Genomic medicine in cardiovascular disease: introduction.

PMID- 24932353
TI  - Dr. Robert Roberts oversees special issue on genomic medicine for the Methodist
      DeBakey Cardiovascular Journal.

PMID- 24932355
TI  - Sequencing your genome: what does it mean?
AB  - The human genome contains approximately 3.2 billion nucleotides and about 23,500
      genes. Each gene has protein-coding regions that are referred to as exons. The
      human genome contains about 180,000 exons, which are collectively called an
      exome. An exome comprises about 1% of the human genome and hence is about 30
      million nucleotides in size. Today's technologies afford the opportunity to
      sequence all nucleotides in the human exome and even in the human genome. Given
      that more than three-quarters of the known disease-causing variants are located
      in the exome, and considering the cost and technical challenges in analyzing the
      whole genome sequence data, the focus of present research is primarily on whole
      exome sequencing (WES). While WES at the medical sequencing level is still
      expensive, it is becoming more affordable. Cost will not likely be a major
      barrier in the near future, and the data analysis is becoming less tedious. The
      most difficult challenge at the heart of medical sequencing is interpreting the
      findings. Each exome contains about 13,500 single nucleotide variants (SNVs) that
      affect the amino acid sequence, and a large number are expected to be functional
      variants. The daunting task is to distinguish the variants that are pathogenic
      from those that have minimal or no discernible clinical effects. While various
      algorithms exist, none are sufficiently robust. Thus, in-depth knowledge in
      genetics and medicine is essential for the proper interpretation of the WES
      findings. This review will discuss the potential applications of the WES data in
      the practice of cardiovascular medicine.

PMID- 24932356
TI  - Genetics of coronary artery disease: an update.
AB  - In 2007, the first genetic risk variant, 9p21, was simultaneously discovered by
      two independent groups. 9p21 increases the risk of coronary artery disease in
      individuals with premature heart disease by twofold, and in the overall
      population the heterozygote is associated with a 25% increased risk and the
      homozygote with a 50% increased risk. It is of note that the risk mediated by
      9p21 is independent of known risk factors. Since then, with the development of
      new technologies and the international consortium of CARDIoGRAM, there is now a
      total of 50 genetic risk variants confirmed and replicated for CAD. Of these 50,
      35 mediate their risk by unknown mechanisms, indicating that the pathogenesis of
      atherosclerosis and myocardial infarction is due to additional factors as yet
      unknown. The role of genetic risk factors in the management of CAD is yet to be
      determined. Since many of them are independent of known risk factors, the genetic
      risk will in the future have to be incorporated into the guidelines, which
      recommend the target level of plasma LDL-C to be achieved based on the number of
      risk factors.

PMID- 24932357
TI  - Cardiovascular drugs and the genetic response.
AB  - The emergence of personalized medicine mandates a complete understating of DNA
      sequence variation that modulates drug response. Initial forays have been made in
      the cardiac arena, yet much remains to be elucidated in the pharmacogenetics of
      cardiac drugs. Most progress has been made in describing DNA sequence variation
      related to the anticoagulant warfarin and the antiplatelet drug clopidogrel. This
      includes a description of DNA sequence variation that underlies pharmacokinetic
      and pharmacodynamic variability, the impact of such variation on predicting hard
      outcomes, and the ability of genotype-guided prescription to facilitate rapid
      titration to a therapeutic range while avoiding unnecessary high plasma levels.
      Nuanced prescription will require a complete inventory of DNA sequence variants
      that underlie drug-related side effects.

PMID- 24932358
TI  - A contemporary review on the genetic basis of atrial fibrillation.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia, and affected
      individuals suffer from increased rates of heart failure, stroke, and death.
      Despite the enormous clinical burden that it exerts on patients and health care
      systems, contemporary treatment strategies have only modest efficacy that likely
      stems from our limited understanding of its underlying pathophysiology.
      Epidemiological studies have provided unequivocal evidence that the arrhythmia
      has a substantial heritable component. Subsequent investigations into the
      genetics underlying atrial fibrillation have suggested that there is considerable
      interindividual variability in the pathophysiology characterizing the arrhythmia.
      This heterogeneity may partly account for the poor treatment efficacy of current
      therapies. Subdividing atrial fibrillation into mechanistic subtypes on the basis
      of genotype illustrates the heterogeneous nature of the arrhythmia and may
      ultimately help guide treatment strategies. A pharmacogenetic approach to the
      management of atrial fibrillation may lead to dramatic improvements in treatment
      efficacy and improved patient outcomes.

PMID- 24932359
TI  - Brugada syndrome.
AB  - Brugada syndrome is a rare cardiac arrhythmia characterized by
      electrocardiographic right bundle branch block and persistent ST-segment
      elevation in the right precordial leads. It is associated with ventricular
      fibrillation and a high risk for sudden cardiac death, predominantly in younger
      males with structurally normal hearts. Patients can remain asymptomatic, and
      electrocardiographic patterns can occur both spontaneously or after
      pharmacological induction. So far, several pathogenic genes have been identified
      as associated with the disease, but SCN5A is the most prevalent one. Two
      consensus reports to define the diagnostic criteria, risk stratification, and
      management of patients have been published in the last few years. This brief
      review focuses on the recent clinical diagnosis, genetic basis, and advances in
      pharmacological treatment of Brugada syndrome.

PMID- 24932360
TI  - Genetics of long QT syndrome.
AB  - Long QT syndrome (LQTS) is a potentially life-threatening cardiac arrhythmia
      characterized by delayed myocardial repolarization that produces QT prolongation
      and increased risk for torsades des pointes (TdP)-triggered syncope, seizures,
      and sudden cardiac death (SCD) in an otherwise healthy young individual with a
      structurally normal heart. Currently, there are three major LQTS genes (KCNQ1,
      KCNH2, and SCN5A) that account for approximately 75% of the disorder. For the
      major LQTS genotypes, genotype-phenotype correlations have yielded gene-specific
      arrhythmogenic triggers, electrocardiogram (ECG) patterns, response to therapies,
      and intragenic and increasingly mutation-specific risk stratification. The 10
      minor LQTS-susceptibility genes collectively account for less than 5% of LQTS
      cases. In addition, three atypical LQTS or multisystem syndromic disorders that
      have been associated with QT prolongation have been described, including ankyrin
      B syndrome, Anderson-Tawil syndrome (ATS), and Timothy syndrome (TS). Genetic
      testing for LQTS is recommended in patients with either a strong clinical index
      of suspicion or persistent QT prolongation despite their asymptomatic state.
      However, genetic test results must be interpreted carefully.

PMID- 24932362
TI  - Calcified amorphous tumor of the heart: case report and review of the literature.
AB  - Calcified amorphous tumor of the heart (cardiac CAT) is a rare non-neoplastic
      cardiac mass that mimics malignancy on imaging and can cause symptoms due to flow
      obstruction or embolization of calcific fragments. We report a 57-year-old female
      with multiple medical problems affected by cardiac CAT. The echocardiogram showed
      a 2 x 1.7 cm right atrial mass. Under the clinical diagnosis of cardiac myxoma, a
      mass resection was performed. Microscopic examination of the resected mass showed
      nodular calcified amorphous debris with admixed degenerated fibrin and focal
      chronic inflammation. At the 1-year follow-up, the patient was free of disease.
      We performed a literature review of 16 previously reported cases. Histologically,
      a cardiac CAT consists of calcification and eosinophilic amorphous material in
      the background of dense collagenous fibrous tissue. A review of these cases shows
      a wide range of age at diagnosis and slight female predominance. The patients are
      either asymptomatic at presentation or complain of shortness of breath. The
      tumors have been found in all chambers of the heart, most commonly in the left
      ventricle. The sizes of the tumors range from 0.17 to 4 cm, with 62.5% of the
      tumors being mobile. Among the nine cases with documented follow-up study, all
      but one was free of disease and only one case of relapse was recorded. In
      conclusion, cardiac CATs are frequently asymptomatic at presentation, size is
      equal to or less than 4 cm, they can be located in all four chambers and are
      usually mobile, and they may relapse when not completely excised.

PMID- 24932361
TI  - The Brockenbrough-Braunwald-Morrow sign.
AB  - Hypertrophic cardiomyopathy is a relatively common genetic disorder and usually
      asymptomatic. However, approximately 25% of patients develop left ventricular
      outflow obstruction and can develop angina, syncope, or congestive heart failure.
      Initiation and titration of beta-blockade usually results in symptomatic
      improvement. Patients with medically refractory symptoms can see further
      symptomatic improvement and relief of obstruction with either surgical myectomy
      or alcohol septal ablation (ASA). Although surgical myectomy has been the gold
      standard, ASA has been shown in nonrandomized studies and a meta-analysis to be
      comparable. In patients undergoing ASA without a rest obstruction, the
      Brokenbrough-Braunwald-Morrow sign can be used to accurately determine the degree
      of left ventricular outflow tract (LVOT) obstruction prior to, during, and after
      ASA.

PMID- 24932363
TI  - A tool to assess mobility status in critically ill patients: the Perme Intensive
      Care Unit Mobility Score.
AB  - The benefits of early mobilization for adult patients in the intensive care unit
      (ICU) are reduced length of ICU and hospital stays, fewer readmissions to the
      ICU, decreased duration of mechanical ventilation, fewer days of detrimental
      bedrest, minimal adverse or unsafe events, and improved walking distance. Because
      there are no available tools to specifically measure mobility status of patients
      in the ICU setting, there is an urgent need to create a reliable tool that
      measures and standardizes the assessment of mobility status for these patients.
      The purpose of this study was to describe the development of this novel ICU
      specific tool to assess a patient's mobility status, examine the initial
      reliability of the tool, and address its clinical application. The Perme ICU
      Score was quickly and easily administered by physical therapists. Overall, the
      inter-rater agreement was 94%. A total of six items had kappa values of < .6, and
      these low scores may have been the result of the procedure to collect inter-rater
      scores, wherein one rater assisted with the activity while a second rater
      observed. In order to improve reliability, the authors developed directions to
      standardize the assessment. The Perme ICU Mobility Score is a tool developed to
      measure the patient's mobility status starting with the ability to follow
      commands and culminating in the distance walked in two minutes. Preliminary data
      suggest that the validity of this tool is supported by expert concurrence, its
      overall reliability is high, and its clinical use is acceptable.

PMID- 24932364
TI  - Physician competence: a perspective from the practicing cardiologist.
AB  - All cardiologists strive to be "competent" physicians. It is important for both
      the certifying bodies and our patients to know that we are highly competent in
      our practice of cardiovascular disease. This is especially true in the current
      era, with its knowledge explosion and exponential growth in diagnostic and
      therapeutic procedures. However, physician competence has never been clearly
      defined, much less measured. The American Board of Medical Subspecialties and the
      Accreditation Council for Graduate Medical Education (ACGME) have defined six
      domains for physician competence, including medical knowledge, patient care,
      communication, practice-based learning, system-based practice, and interpersonal
      relationships-terminology that has remained unclear to practicing cardiologists.
      This paper presents a simplistic view of what a cardiologist must achieve to be
      considered a competent physician and discuss the role of professional societies
      and academic medical centers in facilitating the attainment and documentation of
      competence for all of us.

PMID- 24932367
TI  - Museum of TMH Multimodality Imaging Center: Evaluation of mechanical aortic valve
      endocarditis and fistula formation by cardiac computed tomography.

PMID- 24932368
TI  - Museum of TMH Multimodality Imaging Center: Native valve pseudoaneurysm.

PMID- 24932369
TI  - Points to remember: Tips on heparin-induced thrombocytopenia (HIT).

PMID- 24932370
TI  - Letter to the editors: IgG4-related inflammatory pseudotumor in the heart.

PMID- 24932372
TI  - In memoriam: Walter Samuel "Sam" Henly: January 30, 1927 - February 10, 2013.

PMID- 24932373
TI  - Performing colonoscopy in elderly and very elderly patients: Risks, costs and
      benefits.
AB  - Many diagnostic and screening colonoscopies are performed on very elderly
      patients. Although colonoscopic yield increases with age, the potential benefits
      in such patients decrease because of shorter life expectancy and more frequent
      comorbidities. Colonoscopy in very elderly patients carries a greater risk of
      complications and morbidity than in younger patients, and is associated with
      lower completion rates and higher likelihood of poor bowel preparation. Thus,
      screening colonoscopy in very elderly patients should be performed only after
      careful consideration of potential benefits, risks and patient preferences. On
      the other hand, diagnostic and therapeutic colonoscopy are more likely to benefit
      even very elderly patients, and in most cases should be performed if indicated. 

PMID- 24932374
TI  - Colonoscopy, pain and fears: Is it an indissoluble trinomial?
AB  - Colonoscopy is the reference method in the secondary prevention, diagnosis and,
      in some cases, treatment of colorectal cancer. It can often cause pain associated
      with embarrassment, anxiety, and physical and emotional discomfort. Pain
      intensity is influenced by a lot of factors, and there is a strict relationship
      among pain, pain perception, and mind. Several methods can be used to break the
      trinomial colonoscopy, pain and fear. Sedoanalgesia is recommended by several
      guidelines. If no sedation is offered, the patient must accept a higher chance of
      unacceptable discomfort and the endoscopist a lower chance of completing the
      procedure because of patient discomfort. Other non-pharmacologic methods such as
      acupuncture, music, and hydrocolonoscopy can be used as alternatives to
      pharmacologic sedoanalgesia. Furthermore, new endoscopic technologies such as
      variable-stiffness colonoscopes and ultrathin colonoscopes, or the use of carbon
      dioxide instead of air for colon insufflation, can reduce the pain caused by
      colonoscopy. In the future, technical improvements such as wireless capsules or
      robotic probes, will probably enable to overcome the present concept of
      colonoscopy, avoiding the use of traditional endoscopes. However, at present the
      poor attention paid by endoscopists to the pain and discomfort caused by
      colonoscopy can not be justified. There are several methods to reduce pain and
      anxiety and to break the trinomial colonoscopy, pain and fear. We must use them. 

PMID- 24932375
TI  - Role of simulation in training the next generation of endoscopists.
AB  - The use of simulation based training in endoscopy has been increasingly
      described, simulation has the potential reduce the harm caused to patients by
      novices performing procedures, increase efficiency by reducing the time needed to
      train in the clinical environment and increase the opportunity to repeatedly
      practice rare procedures as well as allowing the assessment of performance.
      Simulators can consist of mechanical devices, employ cadaveric animal tissue or
      use virtual reality technology. Simulators have been used to teach upper and
      lower gastrointestinal endoscopy as well as interventional procedures. This
      review reviews the currently available endoscopic simulators, and the evidence
      for their efficacy, demonstrating that the ability of simulators to differentiate
      between novice and expert endoscopists is well established. There is limited
      evidence for improved patient outcome as a result of simulation training. We also
      consider how the environment within which a simulation is placed can be
      manipulated to alter the learning achieved, broadening the scope of simulation to
      develop communication as well as technical skills. Finally the implications for
      future practice are considered; technology is likely improve the fidelity of
      simulators, increasing the potential for simulation to improve patient outcomes.
      The impact of the simulation environment, and the correct place of simulation
      within the training curriculum are both issues which need addressing. 

PMID- 24932376
TI  - Monitoring salivary amylase activity is useful for providing timely analgesia
      under sedation.
AB  - AIM: To detect the criteria and cause of elevated salivary amylase activity
      (sAMY) in patients undergoing endoscopic submucosal dissection (ESD) under
      sedation. METHODS: A total of 41 patients with early gastric cancer removed via
      ESD under deep sedation (DS) were enrolled. The perioperative sAMY, which was
      shown as sympathetic excitements (SE), was measured. The time at which a patient
      exhibited a relatively increased rate of sAMY compared with the preoperative
      baseline level (IR, %) >= 100% (twice the actual value) was assumed as the moment
      when the patient received SE. Among the 41 patients, we focused on 14 patients
      who exhibited an IR >= 100% at any time that was associated with sAMY elevation
      during ESD (H-group) and examined whether any particular endoscopic procedures
      can cause SE by simultaneously monitoring the sAMY level. If a patient
      demonstrated an elevated sAMY level above twice the baseline level, the
      endoscopic procedure was immediately stopped. In the impossible case of
      discontinuance, analgesic medicines were administered. This study was performed
      prospectively. RESULTS: A total of 26 episodes of sAMY eruption were considered
      moments of SE in the H-group. The baseline level of sAMY significantly increased
      in association with an IR of > 100% at 5 min, with a significant difference (IR
      immediately before elevation/IR at elevation of sAMY = 8.72 +/- 173/958 +/-
      1391%, P < 0.001). However, effective intervention decreased the elevated sAMY
      level immediately within only 5 min, with a significant difference (IR at sAMY
      elevation/immediately after intervention = 958 +/- 1391/476 +/- 1031, P < 0.001).
      The bispectral indices, systolic blood pressure and pulse rates, which were
      measured at the same time, remained stable throughout the ESD. Forceful
      endoscopic insertion or over insufflation was performed during 22 of the 26
      episodes. Release of the gastric wall tension and/or the administration of
      analgesic medication resulted in the immediate recovery of the elevated sAMY
      level, independent of body movement. CONCLUSION: By detecting twice the actual
      sAMY based on the preoperative level, the release of the gastric wall tension or
      the administration of analgesic agents should be considered.

PMID- 24932377
TI  - Predictors of double balloon endoscopy outcomes in the evaluation of
      gastrointestinal bleeding.
AB  - AIM: To identify patients' characteristics associated with double balloon
      endoscopy (DBE) outcomes in investigation of obscure gastrointestinal bleeding
      (OGIB). METHODS: Retrospective study performed at an academic tertiary referral
      center. Evaluated endpoints were clinical factors associated with no diagnostic
      yield or non-therapeutic intervention of DBE performed for OGIB evaluation.
      RESULTS: We included fifty-five DBE between August 2010 and April 2012. The mean
      age of the sample was 67 with 32 males (58.2%). Twenty-four DBE had no diagnostic
      yield and 30 DBE did not require therapy. Non-diagnostic yield was associated
      with performing two or more DBE studies in one day [odds ratio (OR): 13.72, P =
      0.008], absence of blood transfusions within a year of the DBE (OR: 7.16, P =
      0.03) and absence of ulcers or arteriovenous malformations (AVMs) on prior
      esophagogastroduodenoscopy (EGD) or colonoscopy (OR: 19.30, P = 0.033). Non
      therapeutic DBE was associated with performing two or more DBE per day (OR:
      18.579, P = 0.007), gastrointestinal bleeding episode within a week of the DBE
      (OR: 11.48, P = 0.003), fewer blood transfusion requirements prior to DBE (OR:
      4.55, P = 0.036) and absence of ulcers or AVMs on prior EGD or colonoscopy (OR:
      8.47, P = 0.027). CONCLUSION: Predictors of DBE yield and therapeutic
      intervention on DBE include blood transfusion requirements, previous endoscopic
      findings and possibly endoscopist fatigue.

PMID- 24932378
TI  - Efficacy and safety of endoscopic prophylactic treatment with undiluted
      cyanoacrylate for gastric varices.
AB  - AIM: To evaluate the efficacy and safety of undiluted N-butyl-2 cyanoacrylate
      plus methacryloxysulfolane (NBCM) as a prophylactic treatment for gastric varices
      (GV) bleeding. METHODS: This prospective study was conducted at a single tertiary
      care teaching hospital between October 2009 and March 2013. Patients with portal
      hypertension (PH) and GV, with no active gastrointestinal bleeding, were enrolled
      in primary prophylactic treatment with NBCM injection without lipiodol dilution.
      Initial diagnosis of GV was based on endoscopy and confirmed with endosonography
      (EUS); the same procedure was used after treatment to confirm eradication of GV.
      After puncturing the GV with a regular injection needle, 1 mL of undiluted NBCM
      was injected intranasally into GV. The injection was repeated as necessary to
      achieve eradication or until a maximum total volume of 3 mL of NBCM had been
      injected. Patients were followed clinically and evaluated with endoscopy at 3, 6
      and 12 mo. Later follow-ups were performed yearly. The main outcome measures were
      efficacy (GV eradication), safety (adverse events related to cyanoacrylate
      injection), recurrence, bleeding from GV and mortality related to GV treatment.
      RESULTS: A total of 20 patients (15 male) with PH and GV were enrolled in the
      study and treated with undiluted NBCM injection. Only 2 (10%) patients had no
      esophageal varices (EV); 18 (90%) patients were treated with endoscopic band
      ligation to eradicate EV before inclusion in the study. The patients were
      followed clinically and endoscopically for a median of 31 mo (range: 6-40 mo).
      Eradication of GV was observed in all patients (13 patients were treated with 1
      session and 7 patients with 2 sessions), with a maximum injected volume of 2 mL
      NBCM. One patient had GV recurrence, confirmed by EUS, at 6-mo follow-up, and
      another had late recurrence with GV bleeding after 35 mo of follow-up; overall,
      GV recurrence was observed in 2 patients (10%), after 6 and 35 mo of follow-up,
      and GV bleeding rate was 5% (1 patient). Mild epigastric pain was reported by 3
      patients (15%). No mortality or major complications, including embolism, or
      damage to equipment were observed. CONCLUSION: Endoscopic injection with NBCM,
      without lipiodol, may be a safe and effective treatment for primary prophylaxis
      of gastric variceal bleeding.

PMID- 24932379
TI  - Endoscopic treatment of duodenal fistula after incomplete closure of ERCP-related
      duodenal perforation.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is an important diagnostic
      and therapeutic modality for various pancreatic and biliary diseases. The most
      common ERCP-induced complication is pancreatitis, whereas hemorrhage,
      cholangitis, and perforation occur less frequently. Early recognition and prompt
      treatment of these complications may minimize the morbidity and mortality. One of
      the most serious complications is perforation. Although the incidence of duodenal
      perforation after ERCP has decreased to < 1.0%, severe cases still require
      prolonged hospitalization and urgent surgical intervention, potentially leading
      to permanent disability or mortality. Surgery remains the mainstay treatment for
      perforations of the luminal organs of the gastrointestinal tract. However,
      evidence from case reports and case series support a beneficial role of
      endoscopic clipping in the closure of these defects. Duodenal fistulas are
      usually a result of sphincterotomies, perforated duodenal ulcers, or gastrectomy.
      Other causative factors include Crohn's disease, trauma, pancreatitis, and
      cancer. The majority of duodenal fistulas heal with nonoperative management.
      Those that fail to heal are best treated with gastrojejunostomy. Recently
      proposed endoscopic approaches for managing gastrointestinal leaks caused by
      fistulas include fibrin glue injection and positioning of endoclips. Our patient
      developed a secondary persistent duodenal fistula as a result of previous
      incomplete closure of duodenal perforation with hemoclips and an endoloop. The
      fistula was successfully repaired by additional clipping and fibrin glue
      injection. 

PMID- 24932381
TI  - Guilt by Association: The Physical Chemistry and Biology of Protein Aggregation.

PMID- 24932380
TI  - How to Get Insight into Amyloid Structure and Formation from Infrared
      Spectroscopy.
AB  - There is an enormous amount of interest in the structures and formation
      mechanisms of amyloid fibers. In this Perspective, we review the most common
      structural motifs of amyloid fibers and discuss how infrared spectroscopy and
      isotope labeling can be used to identify their structures and aggregation
      kinetics. We present three specific strategies, site-specific labeling to obtain
      residue-by-residue structural information, isotope dilution of uniformly labeled
      proteins for identifying structural folds and protein mixtures, and expressed
      protein ligation for studying the domain structures of large proteins. For each
      of these methods, vibrational couplings are the source of the identifying
      features in the infrared spectrum. Examples are provided using the proteins
      hIAPP, Abeta, polyglutamine, and gammaD-crystallin. We focus on FTIR spectroscopy
      but also describe new observables made possible by 2D IR spectroscopy.

PMID- 24932382
TI  - Stress Intervention and Disease in African American Lupus Patients: The Balancing
      Lupus Experiences with Stress Strategies (BLESS) Study.

PMID- 24932383
TI  - Malaria vaccine: a future hope to curtail the global malaria burden.
AB  - It has been estimated that nearly half of the world's population is at the risk
      of contracting malaria with sub Saharan Africa being the most risky area. The
      existing frontline malaria control interventions are not only expensive but also
      become ineffective owing to the emergence of insecticide and drug resistance. It
      calls for an innovative approach in terms of potential and reliable vaccine as an
      additional tool. Over centuries, the public health experts have been actively
      engaged to formulate a safe, affordable and potential malaria vaccine and
      accordingly a notable achievement has also been attained. However, many
      challenges are required to be flagged immediately and effectively to devise an
      ideal prophylactic malaria vaccine. Therefore, the global community has to remain
      waiting quite a few more years to build a wannabe malaria-free world in the near
      future. 

PMID- 24932384
TI  - Protein-energy Malnutrition in Goitrous Schoolchildren of Isfahan, Iran.
AB  - BACKGROUND: Some studies have shown the possible role of protein-energy
      malnutrition (PEM) in persistence of endemic goiter in iodine replenished areas.
      The present study was conducted to assess the association between PEM and goiter
      in schoolchildren of Isfahan, Iran. METHODS: In a cross-sectional study using
      multistage cluster random-sampling, 2331 schoolchildren with age ranged from 6-13
      years old with a female to male ratio of 1.60 were enrolled. Thyroid size was
      examined by two endocrinologists for goiter detection. Children were considered
      goitrous if they had palpable or visible goiters according to World Health
      Organization (WHO)/United Nations children's Fund/International Council for the
      Control of Iodine Deficiency criteria. Weight and standing height were measured
      using the standard tools and anthropometric indices were calculated using the WHO
      AnthroPlus software developed by the World Health Organization. Height-for-age Z
      scores (HAZ), weight-for-age Z-scores (WAZ) and body mass index (BMI) for age
      were calculated for each child. Children with a HAZ, WAZ or BMI-for-age of Z
      score < -2.0 were classified as stunted, underweight or thin, respectively. Blood
      samples were drowned to measure serum thyroid hormones. RESULTS: Overall, 32.9%
      of subjects were classified as goitrous. Weight, height, BMI, WAZ and BMI-for-age
      Z-score were significantly lower in children with goiter than in children who did
      not have goiter (P < 0.05). The prevalence of goiter in thin children was higher
      than that in non-thin ones (48.4 vs. 31.6%, odds ratio [OR]: 2.02, 95% confidence
      interval [CI]: 1.52-2.69, P < 0.001). Although 33.4% of non-stunted children were
      goitrous, 31% of stunted ones had goiter (P = 0.5). According to the logistic
      regression model taking sex and age as covariates, the only significant parameter
      affecting palpable goiter detection was thinness (OR = 2.13, 95% CI: 1.22-3.69, P
      < 0.001). CONCLUSIONS: In the present study, we found a high prevalence of goiter
      in children who were malnourished. It seems that PEM may play a role in the still
      high prevalence of goiter in this region.

PMID- 24932385
TI  - Adverse health problems among municipality workers in alexandria (egypt).
AB  - BACKGROUND: Solid waste management has emerged as an important human and
      environmental health issue. Municipal solid waste workers (MSWWs) are potentially
      exposed to a variety of occupational biohazards and safety risks. The aim of this
      study was to describe health practices and safety measures adopted by workers in
      the main municipal company in Alexandria (Egypt) as well as the pattern of the
      encountered work related ill health. METHODS: A cross-sectional study was
      conducted between January and April 2013. We interviewed and evaluated 346
      workers serving in about 15 different solid waste management activities regarding
      personal hygiene, the practice of security and health care measures and the
      impact of solid waste management. RESULTS: Poor personal hygiene and self-care,
      inadequate protective and safety measures for potentially hazardous exposure were
      described. Impact of solid waste management on health of MSWWs entailed high
      prevalence of gastrointestinal, respiratory, skin and musculoskeletal
      morbidities. Occurrence of accidents and needle stick injuries amounted to 46.5%
      and 32.7% respectively. The risk of work related health disorders was notably
      higher among workers directly exposed to solid waste when compared by a group of
      low exposure potential particularly for diarrhea (odds ratio [OR] = 2.2, 95%
      confidence interval [CI] = 1.2-3.8), vomiting (OR = 2.7, 95% CI = 1.1-6.6),
      abdominal colic (OR = 1.9, 95% CI = 1.1-3.2), dysentery (OR = 3.6, 95% CI = 1.3
      10), dyspepsia (OR = 1.8, 95% CI = 1.1-3), low back/sciatic pain (OR = 3.5, 95%
      CI = 1.8-7), tinnitus (OR = 6.2, 95% CI = 0.3-122) and needle stick injury (OR =
      3.4, 95% CI = 2.1-5.5). CONCLUSIONS: Workers exposed to solid waste exhibit
      significant increase in risk of ill health. Physician role and health education
      could be the key to assure the MSWWs health safety.

PMID- 24932386
TI  - A Small-scale Cross-sectional Study for the Assessment of Cardiorespiratory
      Fitness in Relation to Body Composition and Morphometric Characters in Fishermen
      of Araku Valley, Andhra Pradesh, India.
AB  - BACKGROUND: The people residing in coastal areas of Visakhapatnam are mostly
      engaged in fishery, which is always been a physically demanding job, and numerous
      factors have direct or indirect impact on the health of fishermen; but, the data
      about their physical fitness or health status is quite scanty. Thus, the present
      study was conducted to assess their cardiorespiratory fitness pattern, as well as
      morphometric characters, which may be influenced by their occupation. METHODS: In
      this retrospective cohort study, 25 young fishermen (mean age of 22.8 +/- 1.92
      years) were randomly selected from Araku valley of Visakhapatnam District, Andhra
      Pradesh and compared with 25 subjects who were randomly selected from college
      students (mean age of 21.9 +/- 2.25 years) of Kolkata, West Bengal. Some physical
      and physiological fitness variables including height, weight, body mass index,
      body surface area, physical fitness index, anaerobic power, and energy
      expenditure were measured along with their morphometric characters. RESULTS:
      Analysis of data indicated a significant difference in blood pressure, physical
      fitness index, energy expenditure, body fat percent and anaerobic power among
      fishermen compared to controls. However, there were no changes in morphometric
      characters between the two groups. CONCLUSIONS: Findings of this small-scale
      population-based study indicated that health and physical fitness of young
      fishermen is under the influence of both occupational workload and nutritional
      status, as found by body composition and morphometric characters.

PMID- 24932387
TI  - The therapeutic effect of the aqueous extract of boswellia serrata on the
      learning deficit in kindled rats.
AB  - BACKGROUND: It has been reported that epilepsy is a disorder of the central
      nervous system that causes memory impairment. This study examines the role of the
      aqueous extract of Boswellia on the learning disability of the pentylenetetrazol
      (PTZ)-induced kindled rats. METHODS: In this experimental study, 64 male rats
      were used. Kindling seizures were induced by three injections of 25 mg/kg of PTZ
      every 15 min. Control animals received normal saline instead. To evaluate the
      therapeutic effect of Boswellia extract on the PTZ-induced cognitive deficits,
      the aqueous extract (0, 0.1, 0.5 or 1 g/kg, i.p.) were administrated to all
      animals for three consecutive days. At 24 h later, passive avoidance learning of
      animals was examined using shuttle box apparatus, respectively. The time required
      for the animal stepping through the dark chamber was determined as step-through
      latency (STL). Data were subjected to the t-test and analysis of variance and
      followed by Tukey's test for multiple comparisons. RESULTS: The STL of the
      kindled rats was significantly reduced compared with control ones (22/375 +/-
      4/19 for kindled and 295 +/- 15/71 for control groups, respectively). Aqueous
      extract of Boswellia improved passive-avoidance learning ability in both control
      and PTZ-kindled animals (P < 0.05). CONCLUSIONS: The results can be stated that
      the Boswellia extract is offset by harmful effects of seizures on cognitive
      function and consumption of Boswellia extract increases the learning ability in
      epileptic animals.

PMID- 24932388
TI  - Reducing the incidence of chronic lung disease in very premature infants with
      aminophylline.
AB  - BACKGROUND: The objective of this study is to assess the safety and preventative
      effects of aminophylline on the incidence of chronic lung disease (CLD) in very
      premature infants. METHODS: This was a long follow-up randomized clinical trial.
      The prophylactic effect of aminophylline on the incidence of CLD was investigated
      in very premature infants. The study group received aminophylline for the 1(st)
      10 days of life and control infants received no aminophylline during the 1(st) 10
      days of life. RESULTS: Fifty-two infants participated (26 aminophylline, 26
      controls). Premature infants on aminophylline had clearly shorter oxygen
      dependency time than those in the control group. Median time of oxygen dependency
      was 3 (0-9.5) days and 14 (3-40.5) days in group A and C, respectively (P:
      0.001). Incidence of CLD was significantly different between the two groups. Only
      two infants (8.7%) on aminophylline developed CLD, when compared to 11 infants
      (44.0%), who did not receive aminophylline (P: 0.006). No side-effects were
      reported in the neonates (P: 1). CONCLUSIONS: This study supports the
      preventative effects of aminophylline on the incidence of CLD in very premature
      infants. In other words, the more premature the infants, the greater will be the
      preventative effect of aminophylline on the incidence of CLD.

PMID- 24932389
TI  - Effect of Life Skills Training on Drug Abuse Preventive Behaviors among
      University Students.
AB  - BACKGROUND: Drug abuse is now-a-days one of the gravest social harms. Recent
      years have experienced a drastic rise in drug abuse among school and university
      students. Thus, the need for special attention to the issue is deemed important.
      The present study was conducted with the aim of assessing the impact of life
      skills training on promotion of drug abuse preventive behaviors. METHODS: This
      field trial experimental study was conducted on 60 students of Gonabad Medical
      University selected through quota random sampling and assigned randomly into two
      Intervention and control groups. Data were collected through a questionnaire,
      including two sections of demographic information and drug abuse preventive
      behaviors. The questionnaire was first assessed as to its validity and
      reliability and then administered both before and after educational intervention
      and also as a follow-up 4 years after intervention - Data were then analyzed
      using t-tests and Chi-square. RESULTS: Comparison of post-test mean scores of
      drug abuse preventive behaviors of both groups showed a significant difference (P
      < 0.01) which remained stable 4 years after intervention. There was a significant
      relationship between father's educational level and drug abuse preventive
      behaviors (P < 0.01). CONCLUSIONS: Life skills' training is effective in the
      promotion of drug abuse preventive behaviors of university students.

PMID- 24932390
TI  - Comparative Study of Microtubule-associated Protein-2 and Glial Fibrillary Acidic
      Proteins during Neural Induction of Human Bone Marrow Mesenchymal Stem Cells and
      Adipose-Derived Stem Cells.
AB  - BACKGROUND: In recent years, adipose tissue, due to the stem cells contained
      within, has found a new special place in laboratory and clinical applications.
      These adipose-derived stem cells (ADSCs) have the same characteristics of bone
      marrow mesenchymal stem cells (BMSCs). Although bone marrow (BM) is not easily
      accessible and its procurements may be painful, most patients possess excess fat
      which can be obtained by less invasive methods; this makes adipose tissue
      ubiquitous, available and an ideal large-scale source for research on clinical
      applications. METHODS: BMSCs and ADSCs were harvested from three healthy human
      and were characterized using flow-cytometry. After they were treated for
      neurosphere formation using basic fibroblast growth factor, epidermal growth
      factor, B 27; terminal differentiation was performed. In this study, we used
      immunocytochemistry, real time-polymerase chain reaction and western blotting
      techniques for detection and comparison of Nestin, microtubule-associated protein
      2 (MAP-2) and glial fibrillary acidic protein (GFAP) markers in human ADSCs and
      BMSCs. RESULTS: Under appropriate conditions ADSCs can differentiate into neuron
      like cells and express neural markers the same as BMSCs, also the expression of
      GFAP marker in differentiated cells derived from ADSCs was significantly lower
      than the cells derived from BMSCs (P < 0.05). While the expression of MAP-2
      marker in both groups was the same. CONCLUSIONS: However, due to its advantages
      and according to our results based on the expression levels of GFAP and MAP-2,
      adipose tissue rather than BM could represent a more appropriate stem cell source
      for investigating the application of these cells in understanding the
      pathophysiology and in treatment of neurodegenerative disorders.

PMID- 24932391
TI  - Rate and Risk of All Cause Mortality among People with Known Hypertension in a
      Rural Community of Southern Kerala, India: The Results from the Prolife Cohort.
AB  - BACKGROUND: Hypertension is one of the most important determinants of death due
      to vascular damage and is fast emerging as a high burden disease in India.
      However, its documentation is poor in the country. This study aims to estimate
      the rate and the causal pattern of mortality in a cohort of people with high
      blood pressure as compared to normotensives. METHODS: The study setting is
      Varkkala, a rural village in southern Kerala, India, and the study design was
      that of a prospective cohort. A total of 77,881 participants of age 20 years and
      above were considered for analysis. The rate and risk of all cause mortality
      (death due to any cause) among hypertensives were quantified and compared against
      the normotensives. The causes of death were also analyzedin both the groups. Cox
      proportional hazard models were created to estimate the hazard ratios of death
      among hypertensives adjusted for sociodemographic factors, behaviors, and
      comorbidities. RESULTS: The incidence proportion of deaths in the study was 4.28%
      during the follow-up period of 6 years. The relative risk of mortality was 3.13
      (CI: 2.91-3.37) in the high BP group. The age-adjusted hazard ratio of all cause
      mortality for the high BP group was 2.96 (2.56-3.42). Coronary artery disease was
      the major cause of death among the subjects with high BP. CONCLUSIONS: The study
      revealed high prevalence of hypertension in the study population. A person with
      hypertension is at three times higher risk of death due to any cause compared to
      a normotensive individual even after adjustment for age.

PMID- 24932392
TI  - Bacterial safety of commercial and handmade enteral feeds in an Iranian teaching
      hospital.
AB  - BACKGROUND: This study aimed to investigate and compare the bacterial safety of
      handmade and commercial ready-to-use enteral feeding formulas used in an Iranian
      teaching hospital. METHODS: In this experimental study, a total number of 70
      samples (21 handmade formulas sampled at two sampling times, i.e. the time of
      preparation and 18 h after preparation, and 28 commercial ready-to-use formulas)
      were studied. Total count of viable microorganisms, coliform count and
      Staphylococcus aureus count for all samples were conducted. RESULTS: Out of 42
      handmade samples, 16 samples (76%) had total viable counts greater than 10(3)
      CFU/g in the first sampling time and 17 samples (81%) had total viable counts
      greater than 10(3) CFU/g in the second sampling time. Also, 11 (52%) had coliform
      contamination in the first sampling time which reached 76% (16 samples) in the
      second sampling time. Regarding contamination with S. aureus, 5 samples (24%)
      were contaminated in the first- and 13 samples (62%) were contaminated in the
      second-sampling time. Out of 28 commercial formulas, 27 samples (96%) had total
      viable counts greater than 10(3) CFU/g. Also, 24 samples (86%) were contaminated
      with S. aureus and 27 samples (96%) were contaminated with coliforms. In order to
      compare these two formulas, the results of Mann-Whitney test showed that
      contamination of ready-to-use formulas in all three microbiological samples was
      significantly more than that for handmade samples. CONCLUSIONS: The results of
      the present study indicate that the microbial safety of enteral feeding solutions
      in this hospital is much lower than standard values, demonstrating that the
      development of protocols for clean techniques in the preparation, handling and
      storage of both commercial and handmade enteral feeds is necessary.

PMID- 24932393
TI  - Nutritional assessment for primary school children in tehran: an evaluation of
      dietary pattern with emphasis on snacks and meals consumption.
AB  - BACKGROUND: In order to provide better advice for prevention of obesity and
      eating disorders among children, there is a need to have more knowledge of their
      dietary patterns. This study examined meal and snacking patterns of primary
      school children in Tehran. METHODS: A total of 761 male and female primary school
      children from all educational areas in Tehran were recruited in a cross-sectional
      survey. The data was collected by interviewing the students and their mothers or
      caregivers. Information on food consumption patterns was collected by one 24-h
      recall and one snack-oriented food frequency questionnaire which covered a period
      of 1 month. Means, standard deviations, frequencies, percentages, energy and
      nutrient analyzes and nutrient densities were reported. RESULTS: All of the
      students snacked at least once on the day of the survey. Snacks provided 38% of
      total energy intake by the students. Fruits and sweet snacks were consumed by
      almost all of the students during a week. Energy and most nutrient intakes from
      meals were greater than those consumed from snacks. Snacks had a higher density
      of fiber, carbohydrate, calcium, iron, vitamin C, riboflavin and thiamin and had
      a lower density of protein, fat and niacin, compared with main meals. Salty
      snacks such as extruded cheese curls (Cheetos) and chips were not consumed so
      often. CONCLUSIONS: Results provide detailed information about dietary patterns,
      which in turn enable development of targeted messages and/or interventions to
      improve nutritional status of school children.

PMID- 24932394
TI  - The Effects of Tocotrienols Added to Canola Oil on Microalbuminuria,
      Inflammation, and Nitrosative Stress in Patients with Type 2 Diabetes: A
      Randomized, Double-blind, Placebo-controlled Trial.
AB  - BACKGROUND: Tocotrienols (T3) were neglected in the past; today, get attentions
      due to their antioxidant and none-antioxidant activity. The objective of this
      study was to evaluate the effects of the daily intake of 200 mg T3 added in
      canola oil over 8 weeks on microalbuminuria, inflammation, and nitrosative stress
      in type 2 diabetic patients. METHODS: This study was a double-blinded, placebo
      controlled, randomized trial. A total of 50 patients with T2DM and FBS >126 mg/dl
      treated by non-insulin hypoglycemic drugs were randomly assigned to receive
      either 15 ml T3-enriched canola oil (200 mg/day T3) or pure canola oil for 8
      weeks. Urine microalbumin, volume and creatinine levels, serum hs-CRP, and nitric
      oxide (NO) levels were measured before and after intervention. RESULTS: From 50
      patients participated in this study, 44 completed the study. There were no
      significant differences in baseline characteristics, dietary intake, and physical
      activity between groups. Urine microalbumin and serum hs-CRP were declined
      significantly in T3-treated group. At the end of the study, patients who treated
      with T3 had lower urine microalbumin (11 (9, 25) vs. 22 (15, 39.75) nmol/dl, P =
      0.003) and hs-CRP changes (-10.91 +/- 15.5 vs. -9.88 +/- 27.5 Pg/ml, P = 0.048)
      than control group. A non-significant decrease was also observed in serum NO
      level in T3-treated group with no changes in urine volume and creatinine levels.
      CONCLUSIONS: These findings indicate that T3 leads to ameliorate proteinuria and
      can protect the kidney against inflammation (hs-CRP) and nitrosative stress (NO).

PMID- 24932395
TI  - Application of Capture-Recapture for Fine-tuning Uncertainties About National
      Maternal Mortality Estimates.
AB  - BACKGROUND: Maternal mortality ratio (MMR) is one of the main indicators of the
      millennium development goals and its accurate estimation is very important for
      the countries concerned. The objective of this study is to evaluate the
      applicability of capture-recapture (CRC) as an analytical method to estimate MMR
      in countries. METHODS: We used the CRC method to estimate MMR in Iran for 2004
      and 2005, using two data sources: The maternal mortality surveillance system and
      the National Death Registry (NDR). Because the data registry contains errors, we
      defined three levels of matching criteria to enable matching of cases between the
      two systems. Increasing the matching level makes the matching criteria less
      conservative. Because NDR data were missing or incomplete for some provinces, we
      calculated estimates for two conditions: With and without missing/incomplete
      data. RESULTS: According to the CRC method, MMR in 2004 and 2005 were 33 and 25
      in the best-case scenarios respectively and 86 and 59 in the worst-case scenarios
      respectively. These estimates are closer to the ones reported by United Nations
      Agencies published in 2010, 38 and Hogan's study, 30 in 100,000 live births in
      2005. CONCLUSIONS: The MMR estimation by CRC method is slightly different from
      the international studies. CRC can be considered as a cost-effective method, in
      comparison with cross-sectional studies or improvement of vital registration
      systems, which are both costly and difficult. However, to achieve accurate
      estimates of MMR with CRC method and decrease the uncertainty we need to have
      valid databases and the absence of such capacities will limit the applicability
      of this method in developing countries with poor quality health databases.

PMID- 24932396
TI  - Iran's Multiple Indicator Demographic and Health Survey - 2010: Study Protocol.
AB  - BACKGROUND: There is an international emphasis on providing timely and high
      quality data to monitor progress of countries toward Millennium Development
      Goals. Iran's Multiple Indicator Demographic and Health Survey (IrMIDHS) aimed to
      provide valid information on population and health outcomes to monitor progress
      in achieving national priorities and health programs and to assist policy makers
      to design effective strategies for improving health outcomes and equity in access
      to care. METHODS: A cross-sectional multi-stage stratified cluster-random survey
      is conducted through face-to-face household interviews. The sampling frame is
      developed using Iran's 2006 population and housing census. Provincial samples
      ranging are from a minimum of 400 households per province to 6400 households in
      Tehran province. Cluster size is 10 households. The target sample includes 3096
      clusters: 2187 clusters in urban and 909 clusters in rural areas. IrMIDHS
      instruments include three questionnaires: Household questionnaire, women aged 15
      54 questionnaire, children under five questionnaire, supervision and quality
      assessment checklists and data collection sheets and standard weight and height
      measurement tools for under-five children. A cascading decentralized training
      method is used for training data collection and supervision teams. Quality
      assurance procedures are defined for the five steps of conducting the survey
      including: Sampling, training data collection and training teams, survey
      implementation, data entry and analysis. A multi-layer supervision and monitoring
      procedure is established. All the questionnaires are double entered. CONCLUSIONS:
      IrMIDHS will provide valuable data for policymakers in Iran. Designing and
      implementation of the study involve contributions from academics as well as
      program managers and policy makers. The collaborative nature of the study may
      facilitate better usage of its results.

PMID- 24932397
TI  - Management of Recurrent Post-partum Pregnancy Tumor with Localized Chronic
      Periodontitis.
AB  - Pregnancy tumor is a benign, hyperplastic lesion of the gingiva, considered to be
      reactive or traumatic rather than neoplastic in nature. The term pyogenic
      granuloma is a misnomer as it is not filled with pus or granulomatous tissue
      histologically. It is multi factorial in nature, which shows an exaggerated
      response to stimuli such as low grade or chronic irritation, trauma or hormonal
      variations. Higher levels of sex hormones during pregnancy produce effects on sub
      gingival microflora, the immune system, the vasculature and specific cells of
      periodontium which in turn in the presence of local irritants exaggerate the
      lesion. Since the lesion is clinically indistinguishable from other type of
      hyperplastic conditions, histological findings are required for proper diagnosis.
      We present a case report of recurrent pyogenic tumor which showed the evidence of
      pre-existing localized periodontitis with extensive horizontal bone destruction.
      The lesion was excised by electrocautery combined with conventional flap
      procedure after parturition period. During 3 and 6 months follow-up period post
      operative healing showed satisfactory results without recurrence. 

PMID- 24932398
TI  - Significant weight loss may delay or eliminate the need for total knee
      replacement.
AB  - A 48-year-old morbidly obese woman with a left medial meniscal tear and
      moderately severe degenerative joint disease (DJD) reported for 14-month follow
      up visit from arthroscopic surgery. She reported a resolution of pain, swelling
      and an improved range of motion (ROM). The patient was first evaluated 14 months
      ago, and at that time was considered a strong candidate for total knee
      replacement due to her limited (ROM), knee pain, swelling and functional
      impairment. At a 3 month visit prior to her initial evaluation the patient
      voluntarily enrolled in a nutritional and exercise program overseen by a licensed
      personal trainer and kinesiologist. At her final evaluation 14 months later, it
      was noted that in addition to her improved knee symptoms, the patient lost 15% of
      her initial bodyweight and exhibited significant gains in quadriceps strength.
      Her clinical exam and imaging suggested an arrest of progression of her joint
      disease. It was decided mutually by the patient and physician that she was no
      longer a candidate for total knee replacement surgery. Although the association
      between her weight loss and her knee DJD can only be hypothesized, this case
      report may highlight the need to discuss weight loss as an alternative treatment
      modality for end stage DJD. 

PMID- 24932399
TI  - Comparison of the WHO Child Growth Standards with the NCHS for Estimation of
      Malnutrition in Birjand-Iran.
AB  - BACKGROUND: Anthropometric indices are widely used to assess the health and
      nutritional status of children The aim of the present study was determination of
      malnutrition and compare estimates of under nutrition among young children under
      2 years of age from Birjand city of Iran using WHO growth standard and the
      National Center for Health Statistics (NCHS) references. METHODS: The cross
      sectional descriptive study conducted on 822 children under 2 years of age mean z
      scores for weight-for-age and height-for-age and prevalence underweight, stunting
      and wasting were calculated using the new WHO growth standards and compared with
      NCHS references. RESULTS: Compared with NCHS reference, the mean height for age
      were lower and mean weight for age scores were almost similar using the WHO
      standards. Prevalence underweight, stunting, and wasting using WHO standards were
      5.2-8.2% and 1.9%, respectively, compared to 6.5-37.3% and 1% based on the NCHS
      references. CONCLUSIONS: Using WHO standards resulted differences in mean z score
      for height for age and changes in prevalence of stunting compared with NCHS
      references in Birjand city children.

PMID- 24932400
TI  - Determinants of prelacteal feeding in rural northern India.
AB  - BACKGROUND: Prelacteal feeding is an underestimated problem in a developing
      country like India, where infant mortality rate is quite high. The present study
      tried to find out the factors determining prelacteal feeding in rural areas of
      north India. METHODS: A crosssectional study was conducted among recently
      delivered women of rural Uttar Pradesh, India. Multistage random sampling was
      used for selecting villages. From them, 352 recently delivered women were
      selected as the subjects, following systematic random sampling. Chi-square test
      and logistic regression were used to find out the predictors for prelacteal
      feeding. RESULTS: Overall, 40.1% of mothers gave prelacteal feeding to their
      newborn. Factors significantly associated with such practice, after simple
      logistic regression, were age, caste, socioeconomic status, and place of
      delivery. At multivariate level, age (odds ratio (OR) = 1.76, 95% confidence
      interval (CI) = 1.13-2.74), caste and place of delivery (OR = 2.23, 95% CI = 1.21
      4.10) were found to determine prelacteal feeding significantly, indicating that
      young age, high caste, and home deliveries could affect the practice positively.
      CONCLUSIONS: The problem of prelacteal feeding is still prevalent in rural India.
      Age, caste, and place of delivery were associated with the problem. For ensuring
      neonatal health, the problem should be addressed with due gravity, with emphasis
      on exclusive breast feeding.

PMID- 24932401
TI  - Caries risk assessment among school children in davangere city using cariogram.
AB  - BACKGROUND: To assess the caries risk among 12-years old children using the
      Cariogram and to evaluate it by comparing with the actual change in DMFT and DMFS
      over a period of two year. METHODS: A two year prospective study was conducted
      among 12 years age group school going children in Davangere city. At the baseline
      relevant and required information regarding the oral hygiene, diet, fluoride
      usage were obtained using a specially prepared pro forma and the saliva samples
      were collected from study subjects and the required microbiological analysis was
      done, as per the instructions of Cariogram version 1997. Caries experience was
      assessed using DMFT and DMFS index. Re-examination was done after two years and
      caries increment was calculated. The data so obtained was fed into the Cariogram
      software based on which they were divided in five groups which were; 0-20% (high
      risk), 21-40%, 41-60%, 61-80% and 81-100% "Chance of avoiding caries". The caries
      risk profile generated by the software was compared with caries increment over
      two years and subjected to statistical analysis. RESULTS: Eighty nine point
      twenty nine percent of the children in the very low risk group as predicted by
      Cariogram at baseline did not develop new caries lesions by the end of two years
      follow-up. Higher risk children at baseline developed higher number of new
      carious lesions. CONCLUSIONS: Cariogram can be a reliable tool in caries
      prediction. It can aid in identifying different risk groups in a community and
      developing preventive strategies for reducing caries risk in children.

PMID- 24932402
TI  - Odds ratio an important measure in case control study.

PMID- 24932403
TI  - Alternating layer addition approach to CdSe/CdS core/shell quantum dots with near
      unity quantum yield and high on-time fractions.
AB  - We report single-particle photoluminescence (PL) intermittency (blinking) with
      high on-time fractions in colloidal CdSe quantum dots (QD) with conformal CdS
      shells of 1.4 nm thickness, equivalent to approximately 4 CdS monolayers. All QDs
      observed displayed on-time fractions > 60% with the majority > 80%. The high-on
      time-fraction blinking is accompanied by fluorescence quantum yields (QY) close
      to unity (up to 98% in an absolute QY measurement) when dispersed in organic
      solvents and a monoexponential ensemble photoluminescence (PL) decay lifetime.
      The CdS shell is formed in high synthetic yield using a modified selective ion
      layer adsorption and reaction (SILAR) technique that employs a silylated sulfur
      precursor. The CdS shell provides sufficient chemical and electronic passivation
      of the QD excited state to permit water solubilization with greater than 60% QY
      via ligand exchange with an imidazole-bearing hydrophilic polymer.

PMID- 24932404
TI  - Copper-Catalyzed Alkene Diamination: Synthesis of Chiral 2-Aminomethyl Indolines
      and Pyrrolidines.
AB  - Chiral vicinal diamines, including 2-aminomethyl indolines and pyrrolidines, are
      useful as ligands for catalytic asymmetric reactions and are also found as
      important components of bioactive compounds. Herein is reported the first copper
      catalyzed alkene diamination that occurs with high enantioselectivity. The
      substrate range is the broadest yet reported for this kind of intra
      /intermolecular reaction sequence both with respect to gamma-alkenyl sulfonamide
      substrate and external amine nucleophile. The resulting products expand the
      availability of substituted 2-aminomethyl indolines and pyrrolidines, privileged
      compounds in asymmetric catalysis and medicinal chemistry. A unique solution to a
      challenging oxidation problem related to copper catalyst turnover is also
      presented.

PMID- 24932406
TI  - Covalent Immobilization of Collagen on Titanium through Polydopamine Coating to
      Improve Cellular Performances of MC3T3-E1 Cells.
AB  - Surface modification of orthopedic implants is critical for improving the
      clinical performance of these medical devices. Herein, collagen was covalently
      immobilized onto a titanium implant surface via a novel adherent polydopamine
      coating inspired by mussel adhesive proteins. The formation and composition of
      the collagen coating was characterized using X-ray photoelectron spectroscopy
      (XPS) and scanning electron microscopy (SEM). Fluorescent labeled collagen was
      also used to examine the formation and uniformity of the collagen coating. The
      resultant collagen coating with a polydopamine supporting substrate demonstrated
      better uniformity and distribution on the titanium surface compared to a physical
      adsorption of collagen. The covalent immobilized collagen coating is biologically
      active, as evidenced by its ability to enhance MC3T3-E1 cell adhesion, support
      cell proliferation and promote early stage osteogenic differentiation of pre
      osteoblasts. Our study suggests covalent immobilization of collagen through the
      polydopamine coating might be an efficient way to improve the cellular
      performance of implant surfaces.

PMID- 24932405
TI  - Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route
      in young and aged spontaneously hypertensive rats.
AB  - BACKGROUND: Many aspects of CSF dynamics are poorly understood due to the
      difficulties involved in quantification and visualization. In particular, there
      is debate surrounding the route of CSF drainage. Our aim was to quantify CSF
      flow, volume, and drainage route dynamics in vivo in young and aged spontaneously
      hypertensive rats (SHR) using a novel contrast-enhanced computed tomography (CT)
      method. METHODS: ICP was recorded in young (2-5 months) and aged (16 months) SHR.
      Contrast was administered into the lateral ventricles bilaterally and sequential
      CT imaging was used to visualize the entire intracranial CSF system and CSF
      drainage routes. A customized contrast decay software module was used to quantify
      CSF flow at multiple locations. RESULTS: ICP was significantly higher in aged
      rats than in young rats (11.52 +/- 2.36 mmHg, versus 7.04 +/- 2.89 mmHg, p =
      0.03). Contrast was observed throughout the entire intracranial CSF system and
      was seen to enter the spinal canal and cross the cribriform plate into the
      olfactory mucosa within 9.1 +/- 6.1 and 22.2 +/- 7.1 minutes, respectively. No
      contrast was observed adjacent to the sagittal sinus. There were no significant
      differences between young and aged rats in either contrast distribution times or
      CSF flow rates. Mean flow rates (combined young and aged) were 3.0 +/- 1.5
      MUL/min at the cerebral aqueduct; 3.5 +/- 1.4 MUL/min at the 3rd ventricle; and
      2.8 +/- 0.9 MUL/min at the 4th ventricle. Intracranial CSF volumes (and as
      percentage total brain volume) were 204 +/- 97 MUL (8.8 +/- 4.3%) in the young
      and 275 +/- 35 MUL (10.8 +/- 1.9%) in the aged animals (NS). CONCLUSIONS: We have
      demonstrated a contrast-enhanced CT technique for measuring and visualising CSF
      dynamics in vivo. These results indicate substantial drainage of CSF via spinal
      and olfactory routes, but there was little evidence of drainage via sagittal
      sinus arachnoid granulations in either young or aged animals. The data suggests
      that spinal and olfactory routes are the primary routes of CSF drainage and that
      sagittal sinus arachnoid granulations play a minor role, even in aged rats with
      higher ICP.

PMID- 24932407
TI  - Confounding by indication affects antimicrobial risk factors for methicillin
      resistant Staphylococcus aureus but not vancomycin-resistant enterococci
      acquisition.
AB  - BACKGROUND: Observational studies rarely account for confounding by indication,
      whereby empiric antibiotics initiated for signs and symptoms of infection prior
      to the diagnosis of infection are then viewed as risk factors for infection. We
      evaluated whether confounding by indication impacts antimicrobial risk factors
      for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      enterococci (VRE) acquisition. FINDINGS: We previously reported several
      predictors of MRSA and VRE acquisition in 967 intensive care unit (ICU) patients
      with no prior history of MRSA or VRE who had an initial negative screening
      culture followed by either a subsequent negative screening culture (controls) or
      positive screening or clinical culture (cases). Within and prior to this
      acquisition interval, we collected demographic, comorbidity, daily device and
      antibiotic utilization data. We now re-evaluate all antibiotics by medical record
      review for evidence of treatment for signs and symptoms ultimately attributable
      to MRSA or VRE. Generalized linear mixed models are used to assess variables
      associated with MRSA or VRE acquisition, accounting for clustering by ward. We
      find that exclusion of empiric antibiotics given for suspected infection affects
      17% (113/661) of antibiotic prescriptions in 25% (60/244) of MRSA-positive
      patients but only 1% (5/491) of antibiotic prescriptions in 1% (3/227) of VRE
      positive patients. In multivariate testing, fluoroquinolones are no longer
      associated with MRSA acquisition, and aminoglycosides are significantly
      protective (OR = 0.3, CI:0.1-0.7). CONCLUSIONS: Neglecting treatment indication
      may cause common empiric antibiotics to appear spuriously associated with MRSA
      acquisition. This effect is absent for VRE, likely because empiric therapy is
      infrequent given the low prevalence of VRE.

PMID- 24932408
TI  - Prevalence and determinants of Campylobacter infection among under five children
      with acute watery diarrhea in Mwanza, North Tanzania.
AB  - BACKGROUND: Campylobacteriosis, a zoonotic bacterial disease observed world-wide,
      is becoming the most commonly recognized cause of bacterial gastroenteritis in
      humans. This study was done to determine the prevalence and determinants of
      Campylobacter infection among under-fives with acute watery diarrhea in Mwanza
      City, Tanzania. METHOD: This cross-sectional hospital-based study was conducted
      at Bugando Medical Centre (BMC) and Sekou Toure Hospital in Mwanza City. All
      inpatients and outpatients under-fives who met the inclusion criteria from
      October 2012 to April 2013 were enrolled in the study. Demographic and clinical
      data were obtained using standardized data collection tools. Stool samples were
      collected for gram staining and culture for Campylobacter spp. on Preston
      selective agar media. In addition, blood slides for malaria and HIV tests were
      done to all patients. RESULTS: A total of 300 children were enrolled with a
      median age of 12 [interquartile range, 8-19] months. Of these, 169 (56.5%) were
      from BMC and 131 (43.7%) from Sekou-Toure hospital. One hundred and seventy
      (56.7%) of the participating children were male. Of 300 under-fives with acute
      watery diarrhea, 29 patients (9.7%) were found to have Campylobacter infection. A
      significant higher number of children with Campylobacter infection were found in
      Sekou Toure hospital compared to BMC [16.0% (21/29) versus 4.7% (8/29), p =
      0.002)]. Age above 2 years was independently found to predict campylobacter
      infection (OR: 2.9, 95% CI 1.1-7.7, p = 0.0037). Of 30 patients with a positive
      blood slide for Plasmodium falciparum, 20.0% were also positive for Campylobacter
      infection (OR: 3.9, 95% CI 1.2-10.1, p = 0.021). CONCLUSION: Campylobacter
      infection shows a comparatively low prevalence in under-fives with acute watery
      diarrhea in Mwanza city and is independently associated with positive slides for
      malaria and an age above 2 years. Further studies are needed to type the most
      prevalent Campylobacter species and to determine their antibiotic susceptibility
      pattern.

PMID- 24932409
TI  - Characterization of Free and Porous Silicon-Encapsulated Superparamagnetic Iron
      Oxide Nanoparticles as Platforms for the Development of Theranostic Vaccines.
AB  - Tracking vaccine components from the site of injection to their destination in
      lymphatic tissue, and simultaneously monitoring immune effects, sheds light on
      the influence of vaccine components on particle and immune cell trafficking and
      therapeutic efficacy. In this study, we create a hybrid particle vaccine platform
      comprised of porous silicon (pSi) and superparamagnetic iron oxide nanoparticles
      (SPIONs). The impact of nanoparticle size and mode of presentation on magnetic
      resonance contrast enhancement are examined. SPION-enhanced relaxivity increased
      as the core diameter of the nanoparticle increased, while encapsulation of SPIONs
      within a pSi matrix had only minor effects on T2 and no significant effect on T2*
      relaxation. Following intravenous injection of single and hybrid particles, there
      was an increase in negative contrast in the spleen, with changes in contrast
      being slightly greater for free compared to silicon encapsulated SPIONs.
      Incubation of bone marrow-derived dendritic cells (BMDC) with pSi microparticles
      loaded with SPIONs, SIINFEKL peptide, and lipopolysaccharide stimulated immune
      cell interactions and interferon gamma production in OT-1 TCR transgenic CD8+ T
      cells. Overall, the hybrid particle platform enabled presentation of a complex
      payload that was traceable, stimulated functional T cell and BMDC interactions,
      and resolved in cellular activation of T cells in response to a specific antigen.

PMID- 24932410
TI  - Immune System Regulation in the Induction of Broadly Neutralizing HIV-1
      Antibodies.
AB  - In this brief review, we discuss immune tolerance as a factor that determines the
      magnitude and quality of serum antibody responses to HIV-1 infection and
      vaccination in the context of recent work. We propose that many conserved,
      neutralizing epitopes of HIV-1 are weakly immunogenic because they mimic host
      antigens. In consequence, B cells that strongly bind these determinants are
      removed by the physiological process of immune tolerance. This structural mimicry
      may represent a significant impediment to designing protective HIV-1 vaccines,
      but we note that several vaccine strategies may be able to mitigate this
      evolutionary adaptation of HIV and other microbial pathogens. 

PMID- 24932412
TI  - Workflow interruptions and failed action regulation in surgery personnel.
AB  - BACKGROUND: Workflow interruptions during surgery may cause a threat to patient's
      safety. Workflow interruptions were tested to predict failure in action
      regulation that in turn predicts near-accidents in surgery and related health
      care. METHODS: One-hundred-and-thirty-three theater nurses and physicians from
      eight Swiss hospitals participated in a cross-sectional questionnaire survey. The
      study participation rate was 43%. RESULTS: Structural equation modeling confirmed
      an indirect path from workflow interruptions through cognitive failure in action
      regulation on near-accidents (p < 0.05). The indirect path was stronger for
      workflow interruptions by malfunctions and task organizational blockages compared
      with workflow interruptions that were caused by persons. The indirect path
      remained meaningful when individual differences in conscientiousness and
      compliance with safety regulations were controlled. CONCLUSION: Task
      interruptions caused by malfunction and organizational constraints are likely to
      trigger errors in surgery. Work redesign is recommended to reduce workflow
      interruptions by malfunction and regulatory constraints.

PMID- 24932411
TI  - Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune
      Correlates.
AB  - Interrogating immune correlates of infection risk for efficacious and non
      efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the
      mechanisms of induction of protective immunity to HIV-1. To date, there have been
      six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA),
      VAX004 (Vaxgen, Inc.), HIV-1 Vaccine Trials Network (HVTN) 502 (Step), HVTN 503
      (Phambili), RV144 (sponsored by the U.S. Military HIV Research Program, MHRP) and
      HVTN 505). Cellular, humoral, host genetic and virus sieve analyses of these
      human clinical trials each can provide information that may point to potentially
      protective mechanisms for vaccine-induced immunity. Critical to staying on the
      path toward development of an efficacious vaccine is utilizing information from
      previous human and non-human primate studies in concert with new discoveries of
      basic HIV-1 host-virus interactions. One way that past discoveries from correlate
      analyses can lead to novel inventions or new pathways toward vaccine efficacy is
      to examine the intersections where different components of the correlate analyses
      overlap (e.g., virus sieve analysis combined with humoral correlates) that can
      point to mechanistic hypotheses. Additionally, differences in durability among
      vaccine-induced T- and B-cell responses indicate that time post-vaccination is an
      important variable. Thus, understanding the nature of protective responses, the
      degree to which such responses have, or have not, as yet, been induced by
      previous vaccine trials and the design of strategies to induce durable T- and B
      cell responses are critical to the development of a protective HIV-1 vaccine. 

PMID- 24932413
TI  - Work-related Stress, Caregiver Role, and Depressive Symptoms among Japanese
      Workers.
AB  - BACKGROUND: In Japan, more than 60% of employees are reported to suffer from
      anxiety and stress. Consequently, Japanese society has begun to address such
      important issues as psychogenic disability and job-related suicide. Furthermore,
      given the aging of society and the surge in the number of elderly people
      requiring care, it is necessary to adequately and proactively support employees
      who care for their elderly relatives. The purpose of the present study was to
      investigate caregiver burden in caring for elderly relatives and work-related
      stress factors associated with mental health among employees. METHODS: We studied
      722 men and women aged 18-83 years in a cross-sectional study. The K10
      questionnaire was used to examine mental health status. RESULTS: The proportion
      of participants with a high K10 score was 15% (n = 106). Having little
      conversation with their supervisor and/or coworkers significantly increased the
      risk of depression [odds ratio (OR) 1.8], as did high job overload (OR 2.7) and
      job dissatisfaction (OR 3.8), compared with employees who frequently conversed
      with their supervisor and/or coworkers. Caring for elderly relatives as a
      prominent characteristic of an employee was a significant risk factor for
      depression (OR 2.1). CONCLUSION: The present study demonstrated that employees
      who were caring for elderly relatives were significantly associated with an
      increased risk of depression. To prevent depressive disorders, it may be
      important to focus on reducing the work-caregiving role conflict, as well as
      enhancing employees' job control and better rewarding their efforts in the
      workplace.

PMID- 24932414
TI  - Do Psychological Factors Increase the Risk for Low Back Pain Among Nurses? A
      Comparing According to Cross-sectional and Prospective Analysis.
AB  - BACKGROUND: This study assesses influences of baseline psychological risk factors
      on prevalence of low back pain (LBP) at baseline and follow-up among nurses.
      METHODS: A prospective longitudinal study was performed at two phases, baseline
      and 1-year follow-up among 246 nurses of university hospitals in Shahroud, Iran.
      A standardized Cultural and Psychosocial Influences on Disability questionnaire
      was used for data collection. Logistic regression was performed for analysis.
      RESULTS: At the baseline of the study, 58.9% of nurses reported back pain in the
      previous 12 months. Age (p = 0.001), belief that work causes pain (p = 0.022),
      and somatization tendency (p = 0.002) significantly increased risk of LBP. At 1
      year follow-up, prevalence of LBP was 45.7% and expectation of back pain at
      baseline (p = 0.016) significantly increased risk of LBP in this phase (p <
      0.05). CONCLUSION: Results indicate that risk factors for prevalence of back pain
      at baseline and 1-year follow-up are different. At baseline, the risk factors are
      age, belief that work causes pain, and somatization tendency, and at follow-up,
      expectation of pain is the major risk factor.

PMID- 24932415
TI  - Occupational exposure to blood and body fluids among health care professionals in
      bahir dar town, northwest ethiopia.
AB  - BACKGROUND: Health care professionals (HCPs) are at high risk of contracting
      blood-borne infections due to their occupational exposure to blood and body
      fluids (BBFs). The incidence of these infections among HCPs are higher in low
      income countries such as Ethiopia. The aim of the study was to investigate the
      extent of occupational exposure to BBFs and its associated factors among HCPs in
      Bahir Dar town, Ethiopia. METHODS: A cross-sectional study was used from October
      1, 2012 to October 30, 2012. Three hundred and seventeen HCPs were included in
      the study using a simple random sampling technique. The data were collected using
      a structured questionnaire and analyzed using SPSS version 16. Bivariate and
      multivariate analyses were used to identify the factors related to exposure to
      BBFs. RESULTS: Two hundred and nine (65.9%) HCPs were exposed to BBFs in the past
      year, of which 29.0% were needlestick injuries. Work experience [adjusted odds
      ratio (AOR) 4.13, 95% confidence interval (CI) 1.56-10.91], inconsistent use of
      gloves (AOR 1.98, 95% CI 1.04-3.43), and not complying with standard precautions
      (AOR 1.80, 95% CI 1.00-3.22) were the factors associated with occupational
      exposure to BBFs. CONCLUSION: A high proportion of HCPs was exposed to BBFs in
      this study. Occupational exposure to BBFs was determined by the use of gloves and
      not complying with standard precautions. Ensuring the availability of gloves,
      training about standard precautions, and motivation of HCPs to implement standard
      precautions should be emphasized to avoid such exposures.

PMID- 24932416
TI  - Analysis of variation in total airborne bacteria concentration to assess the
      performance of biological safety cabinets in microbial laboratories.
AB  - BACKGROUND: The purpose of this study was to compare the concentration of total
      airborne bacteria (TAB) in biosafety cabinets (BSCs) at universities and hospital
      microbial laboratories to assess the performance of BSCs. METHODS: TAB was
      determined by using the single-stage Anderson sampler (BioStage Viable Cascade
      Impactor). The samples were obtained three times (with the BSC turned off and the
      shield open; with the BSC turned off and the shield closed; and with the BSC
      tuned on and operating) from the areas in front of 11 BSCs. RESULTS: TAB
      concentrations of accredited and nonaccredited BSCs were determined. No
      significant differences were observed in the TAB concentrations of the accredited
      BSCs and the nonaccredited BSCs for the areas outside the BSCs in the
      laboratories (p > 0.05). TAB concentrations for the BSCs sampled with the shield
      open and the instrument turned off showed differences based on the sampling site
      outside the BSC in each laboratory. CONCLUSION: These results imply that TAB
      concentration is not altered by the performance of the BSCs or TAB itself and/or
      concentration of TAB outside the BSC is not a good index of BSC performance.

PMID- 24932417
TI  - Meta-analysis: association between wrist posture and carpal tunnel syndrome among
      workers.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a common work-related peripheral
      neuropathy. In addition to grip force and repetitive hand exertions, wrist
      posture (hyperextension and hyperflexion) may be a risk factor for CTS among
      workers. However, findings of studies evaluating the relationship between wrist
      posture and CTS are inconsistent. The purpose of this paper was to conduct a meta
      analysis of existing studies to evaluate the evidence of the relationship between
      wrist posture at work and risk of CTS. METHODS: PubMed and Google Scholar were
      searched to identify relevant studies published between 1980 and 2012. The
      following search terms were used: "work related", "carpal tunnel syndrome",
      "wrist posture", and "epidemiology". The studies defined wrist posture as the
      deviation of the wrist in extension or flexion from a neutral wrist posture.
      Relative risk (RR) of individual studies for postural risk was pooled to evaluate
      the overall risk of wrist posture on CTS. RESULTS: Nine studies met the inclusion
      criteria. All were cross-sectional or case-control designs and relied on self
      report or observer's estimates for wrist posture assessment. The pooled RR of
      work-related CTS increased with increasing hours of exposure to wrist deviation
      or extension/flexion [RR = 2.01; 95% confidence interval (CI): 1.646-2.43; p <
      0.01: Shore-adjusted 95% CI: 1.32-2.97]. CONCLUSION: We found evidence that
      prolonged exposure to non-neutral wrist postures is associated with a twofold
      increased risk for CTS compared with low hours of exposure to non-neutral wrist
      postures. Workplace interventions to prevent CTS should incorporate training and
      engineering interventions that reduce sustained non-neutral wrist postures.

PMID- 24932419
TI  - Work-related Dermatoses in Greece.

PMID- 24932418
TI  - Sex Differences in Relationship between Stress Responses and Lifestyle in
      Japanese Workers.
AB  - BACKGROUND: This study examined the relationships between stress responses and
      lifestyle, including sleeping and eating behaviors, in Japanese workers according
      to sex. METHODS: Questionnaires about stress responses and lifestyle were
      completed by 3,017 workers in a financial enterprise (41.5% men, 58.5% women).
      Data were collected in Japan in August 2011. Participants were classified into
      stress and nonstress groups. Relationships between stress responses and lifestyle
      were investigated using logistic regression analysis with stress response as a
      dependent variable. RESULTS: There were 254 (8.4%) participants in the stress
      group and 2,763 (91.6%) in the nonstress group. The results showed that sleeping
      for shorter periods [odds ratio (OR) = 2.97, 95% confidence interval (CI): 1.58
      5.60] was associated with stress responses in women, whereas we found no
      relationship between stress responses and lifestyle among men. However, working
      overtime was associated with stress responses in men (OR = 2.71, 95% CI: 1.43
      5.15). Eating at night was associated with stress responses in the univariate
      analysis (men: OR = 2.10, 95% CI: 1.16-3.80; women: OR = 1.61, 95% CI: 1.09
      2.39). CONCLUSION: This study showed that stress responses were related to
      lifestyle among women but not among men. Among women, stress responses were
      related to sleeping for shorter periods, whereas they were related to working
      long hours among men. In addition, stress responses were related to eating at
      night in the univariate analysis, although this relationship was not seen in the
      multivariate analysis, in either sex.

PMID- 24932420
TI  - Considerations concerning the epidemiology of occupational dermatoses.

PMID- 24932421
TI  - Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl
      with Bloom syndrome.
AB  - Bloom syndrome (BS) is an inherited genomic instability disorder caused by
      disruption of the BLM helicase and confers an extreme cancer predisposition. Here
      we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at
      age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was
      compound heterozygous for the novel BLM frameshift deletion c.1624delG and the
      previously described c.3415C>T nonsense mutation. Two haematological malignancies
      in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in
      particular in the presence of genotoxic stress.

PMID- 24932422
TI  - Survey of C. difficile-Specific Infection Control Policies in Local Long-Term
      Care Facilities.
AB  - INTRODUCTION: The incidence and severity of Clostridium difficile infection (CDI)
      has been increasing and long-term care facility (LTCF) residents are at high risk
      given their age, co-morbidities, and high antibiotic exposure. Infection control
      policies are crucial for controlling CDI, but there are currently no regulatory
      guidelines in the United States. Therefore, we evaluated infection control
      policies in local LTCFs to define the CDI-specific policies and the
      administrative and staff understanding of CDI, so as to identify perceived
      barriers for compliance. METHODS: IRB approval was sought and exemption granted,
      all 8 local LTCFs were asked to participate. Each facility was visited by study
      personnel who interviewed the administrative Infection Control Practitioner (ICP)
      and 3 - 4 Licensed Practical Nurses (LPNs) with distinct survey format. Infection
      control policies were then compared to the SHEA recommendations for CDI in LTCFs.
      RESULTS: Of the eligible facilities, 75% (n = 6) participated. ICP (n = 6) and
      LPNs (n = 21) were interviewed. All facilities accept residents with active CDI
      and 2 had written CDI-specific infection control policies. All facilities had
      hand hygiene or glove use policies and 2 had policies for the use of sporicidal
      environmental cleaning. No facility restricted antibiotic use. Each facility has
      a policy to instruct their staff through in-services, either annually or upon new
      hire, but 33% (n = 7) LPNs reported no facility-based CDI training. While 80% (n
      = 17) of LPNs felt comfortable with the facility CDI policies, only 11 accurately
      restated it. ICPs felt the most relevant barrier to staff compliance was time
      constraints (n = 4, 67%), however, LPNs felt it was limited knowledge (n = 10,
      48%) and poor communication (n = 2, 10%). DISCUSSION AND CONCLUSIONS: With the
      increasing incidence and severity of CDI in LCTF, few of the facilities surveyed
      had CDI-specific policies. Despite CDI-specific training, there is a perceived
      knowledge and communication gap for staff caring for residents with CDI.

PMID- 24932423
TI  - Characteristics of Task-specific Tremor in String Instrument Players.
AB  - BACKGROUND: In recent studies primary bowing tremor has been described; however,
      tremor frequency has never been quantitatively assessed. In addition to
      describing phenomenological aspects of tremor we thus aimed at assessing tremor
      frequency. Our hypothesis was that primary bowing tremor is similar to the
      phenomenological aspects and frequency of primary writing tremor. METHODS: WE
      QUANTIFIED PRIMARY BOWING TREMOR IN FOUR VIOLINISTS UNDER TWO CONDITIONS: open
      strings and a G major scale. Data were analyzed using empirical mode
      decomposition because it takes into account non-stationarity and non-linearity of
      signals. For each patient we further described tremor phenomenology and assessed
      symptom onset, risk factors, medication, and family history with a structured
      anamnesis. We compare the findings to previous findings for primary bowing tremor
      and primary writing tremor. RESULTS: We mainly found a flexion-extension tremor
      of the wrist with a frequency range of 4.7-6.7 Hz. There was no significant
      difference between the conditions. Mean onset age was 43+/-2.4 years. Medication
      included trihexyphenidyl, propranolol, primidone, and botulinum toxin. We found a
      positive family history in two patients and an injury prior to symptom onset in
      another two patients. Comparison of onset age, frequency range, family history,
      and injuries prior to onset revealed that our findings are very similar to
      previous findings on primary bowing tremor and primary writing tremor.
      DISCUSSION: Our findings confirmed our hypothesis that primary bowing tremor is
      similar to primary writing tremor, with regard to phenomenology and epidemiology
      as well as tremor frequency. There was no difference in tremor frequency between
      conditions, suggesting that tremor is not influenced by bimanual coordination or
      bowing speed. Our findings thus provide new phenomenological aspects and may
      contribute to a better understanding of primary bowing tremor.

PMID- 24932424
TI  - In the Gray Zone in the Fragile X Gene: What are the Key Unanswered Clinical and
      Biological Questions?
AB  - Smaller expansions (41-54 CGG repeats) in the fragile X mental retardation 1
      (FMR1) gene are termed "gray zone" alleles. Only recently has interest in these
      expansions increased due to reporting of phenotypes unique to gray zone carriers
      or similar to those seen in individuals with larger expansions. As minimal
      research has focused on gray zone expansions, this paper asks several questions
      related to this topic. These include the following: What is the definition of the
      gray zone? Is there a risk of developing neurological signs in these carriers?
      Are there secondary gene effects that impact gray zone alleles or a biologic
      advantage to carrying these repeats? How do we counsel patients with gray zone
      expansions? The answers to these questions will help to determine the
      significance of these expansions and provide needed information to the research
      community and clinicians. 

PMID- 24932425
TI  - Patient-reported Needs, Non-motor Symptoms, and Quality of Life in Essential
      Tremor and Parkinson's Disease.
AB  - BACKGROUND: Non-motor symptoms, quality of life, service needs, and barriers to
      care of individuals with movement disorders are not well explored. This study
      assessed these domains within a sample of individuals with essential tremor (ET)
      and Parkinson's disease (PD). METHODS: A survey exploring symptoms, needs, and
      barriers to care was disseminated to a convenience sample (N = 96) of individuals
      with a primary diagnosis of ET (N = 19) or PD (N = 77). RESULTS: Similarities in
      overall quality of life and impact on daily functioning were found across
      individuals with ET and PD. Noteworthy differences included endorsement of
      different types of service needs and utilization patterns and fewer non-motor
      symptoms reported among those with ET (M = 6.1, SD = 2.4) than those with PD (M =
      10.4, SD = 3.4). Non-motor symptoms significantly impacted movement disorder
      related quality of life for both diagnostic groups, but this relationship was
      stronger for individuals with ET, t(12) = 3.69, p = 0.003, beta = 0.73 than with
      PD, t(56) = 4.00, p<0.001, beta = 0.47. Individuals with ET also reported higher
      rates of stigma (31.6% vs. 7.8%) and greater impact of non-motor symptoms on
      emotional well-being, R (2) = 0.37, F(1, 13) = 7.17, p = 0.020. DISCUSSION: This
      is the first study to describe and compare the needs, barriers to care, and
      impact on quality of life of two distinct movement disorder groups. Our results
      support the recent efforts of the field to identify interventions to address the
      non-motor symptoms of movement disorders and indicate need for greater
      appreciation of the specific differences in symptoms and quality of life
      experienced across movement disorder diagnoses.

PMID- 24932426
TI  - Brittle Dyskinesia Following STN but not GPi Deep Brain Stimulation.
AB  - BACKGROUND: The aim was to describe the prevalence and characteristics of
      difficult to manage dyskinesia associated with subthalamic nucleus (STN) deep
      brain stimulation (DBS). A small subset of STN DBS patients experience
      troublesome dyskinesia despite optimal programming and medication adjustments.
      This group of patients has been referred to by some practitioners as brittle STN
      DBS-induced dyskinesia, drawing on comparisons with brittle diabetics
      experiencing severe blood sugar regulation issues and on a single description by
      McLellan in 1982. We sought to describe, and also to investigate how often the
      "brittle" phenomenon occurs in a relatively large DBS practice. METHODS: An
      Institutional Review Board-approved patient database was reviewed, and all STN
      and globus pallidus internus (GPi) DBS patients who had surgery at the University
      of Florida from July 2002 to July 2012 were extracted for analysis. RESULTS:
      There were 179 total STN DBS patients and, of those, four STN DBS (2.2%) cases
      were identified as having dyskinesia that could not be managed without the
      induction of an "off state," or by the precipitation of a severe dyskinesia
      despite vigorous stimulation and medication adjustments. Of 75 GPi DBS cases
      reviewed, none (0%) was identified as having brittle dyskinesia. One STN DBS
      patient was successfully rescued by bilateral GPi DBS. DISCUSSION: Understanding
      the potential risk factors for postoperative troublesome and brittle dyskinesia
      may have an impact on the initial surgical target selection (STN vs. GPI) in DBS
      therapy. Rescue GPi DBS therapy may be a viable treatment option, though more
      cases will be required to verify this observation.

PMID- 24932427
TI  - The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and
      Dysfunction: Potential Relevance to Humans.
AB  - In a murine model, we have linked early life toxicant exposure to reduced uterine
      sensitivity to progesterone, a phenotype we had previously associated with
      inflammation in endometriosis patients. Subsequent studies revealed that
      developmental toxicant exposure not only reduces fertility in male and female
      mice but also negatively impacts pregnancy leading to spontaneous preterm birth
      (PTB). An epigenetic alteration of the progesterone receptor gene correlated with
      reduced fertility and adverse pregnancy outcomes and persisted in multiple
      generations of mice in the absence of an additional toxicant exposure. Gene
      environment interactions in women may explain why some patients "at risk" for PTB
      deliver at term while others without known risks deliver early. Our model
      provides a unique system to unravel the interactive influences of inflammation
      and reduced progesterone responsiveness on PTB and suggests that therapy needs to
      begin prior to pregnancy (and involve both partners) rather than once the
      inflammatory cascade has been initiated.

PMID- 24932428
TI  - Chronic Fatigue Syndrome: The Current Status and Future Potentials of Emerging
      Biomarkers.
AB  - Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in
      part due to controversy regarding its definition, biological basis and diagnosis.
      Biomarkers are objective measures that may lead to improvements in our
      understanding of CFS by providing a more coherent and consistent approach to
      study, diagnosis and treatment of the illness. Such metrics may allow us to
      distinguish between CFS subtypes - each defined by characteristic biomarkers -
      currently conflated under the single, heterogeneous condition of CFS. These
      delineations, in turn, may guide more granular, focused, and targeted treatment
      strategies based on more precise characterizations of the illness. Here, we
      review potential CFS biomarkers related to neurological and immunological
      components of the illness, and discuss how these biomarkers may be used to move
      the field of CFS forward, emphasizing clinical utility and potential routes of
      future research.

PMID- 24932429
TI  - Refined Data Analysis Provides Clinical Evidence for Central Nervous System
      Control of Chronic Glaucomatous Neurodegeneration.
AB  - PURPOSE: Refined data analysis was performed to assess binocular visual field
      conservation in patients with bilateral glaucomatous damage to determine whether
      unilateral visual field loss is random, anatomically symmetric, or nonrandom in
      relation to the fellow eye. METHODS: This was a case-control study of 47
      consecutive patients with bilaterally severe glaucoma; each right eye visual
      field locus was paired with randomly selected coisopteric left eye loci, with
      760,000 (10,000 complete sets of 76 loci) such iterations performed per subject.
      The potential role of anatomic symmetry in bilateral visual field conservation
      was also assessed by pairing mirror-image loci of the paired fields. The mean
      values of the random coisopteric and the symmetric mirror pairings were compared
      with natural point-for-point pairings of the two eyes by paired t-test. RESULTS:
      Mean unilateral thresholds across the entire visual field were 18.9 dB left and
      19.9 dB right (average 19.4), 4 dB lower than the better of the naturally paired
      concomitant loci of 23.4 dB (P < 10-15). A remarkable natural tendency for
      conservation of the binocular visual field was confirmed, far stronger than
      explicable by random chance or anatomic symmetry (P < 0.0001), and reaffirmed by
      subsequent prospective simultaneous binocular visual field retesting of an
      arbitrary subset (n = 16) of the study population (P < 0.0001). CONCLUSIONS:
      Refined data analysis of paired visual fields confirms the existence of a natural
      optimization of binocular visual function in severe bilateral glaucoma via
      interlocking fields that could be created only by central nervous system (CNS)
      involvement. TRANSLATIONAL RELEVANCE: Integrated bilateral visual field analysis
      should better define actual visual disability and more accurately reflect the
      functional efficacy of current ocular and future CNS-oriented therapeutic
      approaches to the treatment of glaucoma. Glaucomatous eyes provide a highly
      accessible paired-organ study model for developing therapeutics to optimize
      conservation of function in neurodegenerative disorders.

PMID- 24932431
TI  - Retinal and Choroidal Imaging With 870-nm Spectral-Domain OCT Compared With 1050
      nm Spectral-Domain OCT, With and Without Enhanced Depth Imaging.
AB  - PURPOSE: The purpose of this study was to compare images of the retina and
      choroid obtained with Spectralis 1050-nm spectral-domain optical coherence
      tomography (SD-OCT) with and without enhanced depth imaging (EDI) to the
      commercially available 870-nm SD-OCT with and without EDI. METHODS: Full-length
      30 degrees  line scans were obtained with both 870- and 1050-nm Spectralis OCT
      instruments, with and without EDI. Two trained retina physicians masked to
      wavelength and EDI status assessed the ability to visualize the vitreoretinal
      interface and full-thickness choroid, and subfoveal choroidal thickness (SFCT)
      was measured. RESULTS: Included in the study were 21 eyes. The vitreoretinal
      interface was visualized best with 870-nm OCT without EDI and was diminished with
      1050-nm OCT. Graders preferred 1050 nm with EDI over 870 nm with EDI in
      qualitative comparisons of the choroid; 1050 nm without EDI was slightly
      preferred over 870 nm with EDI but was not statistically significant. SFCT
      measurements correlated well among the imaging modalities except for 870 nm
      without EDI. CONCLUSIONS: SD-OCT with EDI at 870 nm provides good visualization
      of both the vitreoretinal interface and choroid, whereas 1050-nm SD-OCT with or
      without EDI provides more choroidal detail at the expense of visualization of the
      vitreoretinal interface. TRANSLATIONAL RELEVANCE: Use of longer wavelength 1050
      nm SD-OCT provides greater choroidal detail compared with 870-nm SD-OCT, but has
      reduced detail of the vitreoretinal interface. The significance of this trade-off
      for clinical management of retinal disease needs further evaluation.

PMID- 24932432
TI  - Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy.
AB  - PURPOSE: To evaluate the potential utility of collagen-based corneal implants
      with anti-Herpes Simplex Virus (HSV)-1 activity achieved through sustained
      release of LL-37, from incorporated nanoparticles, as compared with cell-based
      delivery from model human corneal epithelial cells (HCECs) transfected to produce
      endogenous LL-37. METHODS: We tested the ability of collagen-phosphorylcholine
      implants to tolerate the adverse microenvironment of herpetic murine corneas.
      Then, we investigated the efficacy of LL-37 peptides delivered through
      nanoparticles incorporated within the corneal implants to block HSV-1 viral
      activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs
      to confer viral resistance, and their response to HSV-1 infection was examined.
      RESULTS: Our implants remained in herpetic murine corneas 7 days longer than
      allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by
      interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but
      could not prevent viral spreading nor clear viruses from the infected cells.
      HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL
      37 inhibited viral binding in vitro but was insufficient to protect cells
      completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the
      incidence of plaque formation and plaque size. CONCLUSION: LL-37 released from
      composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both
      showed anti-HSV-1 activity by blocking binding. However, while both slowed down
      virus spread, neither was able on its own to completely inhibit the viruses.
      TRANSLATIONAL RELEVANCE: LL-37 releasing hydrogels may have potential utility as
      corneal substitutes for grafting in HSV-1 infected corneas, possibly in
      combination with LL-37 producing therapeutic cells.

PMID- 24932430
TI  - The Effect of Age on Optic Nerve Axon Counts, SDOCT Scan Quality, and
      Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in Rhesus Monkeys.
AB  - PURPOSE: To evaluate the effect of age on optic nerve axon counts, spectral
      domain optical coherence tomography (SDOCT) scan quality, and peripapillary
      retinal nerve fiber layer thickness (RNFLT) measurements in healthy monkey eyes.
      METHODS: In total, 83 healthy rhesus monkeys were included in this study (age
      range: 1.2-26.7 years). Peripapillary RNFLT was measured by SDOCT. An automated
      algorithm was used to count 100% of the axons and measure their cross-sectional
      area in postmortem optic nerve tissue samples (N = 46). Simulation experiments
      were done to determine the effects of optical changes on measurements of RNFLT.
      An objective, fully-automated method was used to measure the diameter of the
      major blood vessel profiles within each SDOCT B-scan. RESULTS: Peripapillary
      RNFLT was negatively correlated with age in cross-sectional analysis (P < 0.01).
      The best-fitting linear model was RNFLT(MUm) = -0.40 * age(years) + 104.5 MUm (R2
      = 0.1, P < 0.01). Age had very little influence on optic nerve axon count; the
      result of the best-fit linear model was axon count = -1364 * Age(years) +
      1,210,284 (R2 < 0.01, P = 0.74). Older eyes lost the smallest diameter axons
      and/or axons had an increased diameter in the optic nerve of older animals. There
      was an inverse correlation between age and SDOCT scan quality (R = -0.65, P <
      0.0001). Simulation experiments revealed that approximately 17% of the apparent
      cross-sectional rate of RNFLT loss is due to reduced scan quality associated with
      optical changes of the aging eye. Another 12% was due to thinning of the major
      blood vessels. CONCLUSIONS: RNFLT declines by 4 MUm per decade in healthy rhesus
      monkey eyes. This rate is approximately three times faster than loss of optic
      nerve axons. Approximately one-half of this difference is explained by optical
      degradation of the aging eye reducing SDOCT scan quality and thinning of the
      major blood vessels. TRANSLATIONAL RELEVANCE: Current models used to predict
      retinal ganglion cell losses should be reconsidered.

PMID- 24932433
TI  - An Informational Algorithm as the Basis for Perception-Action Control of the
      Instantaneous Axes of the Knee.
AB  - Traditional locomotion studies emphasize an optimization of the desired movement
      trajectories while ignoring sensory feedback. We propose an information based
      theory that locomotion is neither triggered nor commanded but controlled. The
      basis for this control is the information derived from perceiving oneself in the
      world. Control therefore lies in the human-environment system. In order to test
      this hypothesis, we derived a mathematical foundation characterizing the energy
      that is required to perform a rotational twist, with small amplitude, of the
      instantaneous axes of the knee (IAK). We have found that the joint's perception
      of the ground reaction force may be replaced by the co-perception of muscle
      activation with appropriate intensities. This approach generated an accurate
      comparison with known joint forces and appears appropriate in so far as
      predicting the effect on the knee when it is free to twist about the IAK.

PMID- 24932434
TI  - Direct thermal-UV nanoimprint of an iron-containing organometallic hybrid film.
AB  - Direct thermal-UV nanoimprinting of an organometallic hybrid film has been
      demonstrated to fabricate nanoscale features into a novel organic-inorganic
      solution containing selected metals. The film can be patterned at low temperature
      and pressure, and requires only a short processing time. When analyzed by energy
      dispersion X-ray spectroscopy, the authors observe both organic and metal content
      in the final patterned features. They have also observed that film thermal
      stability increases after UV and oxygen plasma treatments, which may lead to
      devices that perform well across a wide spectrum of temperatures.

PMID- 24932435
TI  - Optically anisotropic infinite cylinder above an optically anisotropic half
      space: Dispersion interaction of a single-walled carbon nanotube with a
      substrate.
AB  - A complete form of the van der Waals dispersion interaction between an infinitely
      long anisotropic semiconducting/insulating thin cylinder and an anisotropic half
      space is derived for all separations between the cylinder and the half space. The
      derivation proceeds from the theory of dispersion interactions between two
      anisotropic infinite half spaces as formulated in Phys. Rev. A 71, 042102 (2005).
      The approach is valid in the retarded as well as nonretarded regimes of the
      interaction and is coupled with the recently evaluated ab initio dielectric
      response functions of various semiconducting/insulating single wall carbon
      nanotubes, enables the authors to evaluate the strength of the van der Waals
      dispersion interaction for all orientation angles and separations between a thin
      cylindrical nanotube and the half space. The possibility of repulsive and/or
      nonmonotonic dispersion interactions is examined in detail.

PMID- 24932436
TI  - Nanostructured silicon membranes for control of molecular transport.
AB  - A membrane that allows selective transport of molecular species requires precise
      engineering on the nanoscale. Membrane permeability can be tuned by controlling
      the physical structure and surface chemistry of the pores. Here, a combination of
      electron beam and optical lithography, along with cryogenic deep reactive ion
      etching, has been used to fabricate silicon membranes that are physically robust,
      have uniform pore sizes, and are directly integrated into a microfluidic network.
      Additional reductions in pore size were achieved using plasma enhanced chemical
      vapor deposition and atomic layer deposition of silicon dioxide to coat membrane
      surfaces. Cross sectioning of the membranes using focused ion beam milling was
      used to determine the physical shape of the membrane pores before and after
      coating. Functional characterization of the membranes was performed by using
      quantitative fluorescence microscopy to document the transport of molecular
      species across the membrane.

PMID- 24932437
TI  - Questioning the Use of PEGylation for Drug Delivery.
AB  - Polyethylene glycol (PEG) is widely utilized in drug delivery and nanotechnology
      due to its reported "stealth" properties and biocompatibility. It is generally
      thought that PEGylation allows particulate delivery systems and biomaterials to
      evade the immune system and thereby prolong circulation lifetimes. However,
      numerous studies over the past decade have demonstrated that PEGylation causes
      significant reductions in drug delivery, including enhanced serum protein
      binding, reduced uptake by target cells, and the elicitation of an immune
      response that facilitates clearance in vivo. This report reviews some of the
      extensive literature documenting the detrimental effects of PEGylation, and
      thereby questions the wisdom behind employing this strategy in drug development. 

PMID- 24932439
TI  - Platelet rich plasma therapies: a great potential to be harnessed.

PMID- 24932438
TI  - Metabolomic Analysis Reveals Amino Acid Responses to an Oral Glucose Tolerance
      Test in Women with Prior History of Gestational Diabetes Mellitus.
AB  - OBJECTIVE: Although gestational diabetes mellitus (GDM) is associated with an
      increased risk of type 2 diabetes mellitus (T2DM) compared to normoglycemic
      pregnancies, the biochemical pathways underlying the progression of GDM to T2DM
      are not fully elucidated. The purpose of this exploratory study was to utilize
      metabolomics with an oral glucose tolerance test (OGTT) to examine the amino acid
      response in women with prior GDM to determine if a relationship between these
      metabolites and established risk factors for T2DM exists. MATERIALS/METHODS:
      Thirty-eight non-pregnant women without diabetes but with prior GDM within the
      previous 3 years were recruited from a community-based population. A 75 g-OGTT
      was administered; fasting and 2-hr plasma samples were obtained. Metabolite
      profiles of 23 amino acids or amino acid derivatives were measured with gas
      chromatography-mass spectrometry. Measures of insulin resistance were derived
      from the OGTT and risk factors for T2DM were obtained by self-report. RESULTS:
      Twenty-two metabolite levels decreased significantly in response to the OGTT
      (p<0.05). The clinical covariates most powerfully associated with metabolite
      level changes included race, body mass index (BMI), and duration of prior
      breastfeeding, (mean +/- SD of standardized beta-coefficients, beta = -0.38 +/-
      0.05, 0.25 +/- 0.08, and 0.44 +/- 0.03, respectively, all p<0.05). Notably, a
      prior history of breastfeeding was associated with the greatest number of
      metabolite changes. CONCLUSIONS: Greater change in metabolite levels after a
      glucose challenge was significantly associated with a longer duration of
      breastfeeding and higher BMI. Further exploration of these preliminary
      observations and closer examination of the specific pathways implicated are
      warranted.

PMID- 24932440
TI  - Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich
      Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine:
      current consensus, clinical implications and perspectives.
AB  - Platelet concentrates for topical and infiltrative use - commonly termed Platetet
      Rich Plasma (PRP) or Platelet-Rich Fibrin (PRF) - are used or tested as surgical
      adjuvants or regenerative medicine preparations in most medical fields,
      particularly in sports medicine and orthopaedic surgery. Even if these products
      offer interesting therapeutic perspectives, their clinical relevance is largely
      debated, as the literature on the topic is often confused and contradictory. The
      long history of these products was always associated with confusions, mostly
      related to the lack of consensual terminology, characterization and
      classification of the many products that were tested in the last 40 years. The
      current consensus is based on a simple classification system dividing the many
      products in 4 main families, based on their fibrin architecture and cell content:
      Pure Platelet-Rich Plasma (P-PRP), such as the PRGF-Endoret technique; Leukocyte-
      and Platelet-Rich Plasma (LPRP), such as Biomet GPS system; Pure Platelet-Rich
      Fibrin (P-PRF), such as Fibrinet; Leukocyte- and Platelet-Rich Fibrin (L-PRF),
      such as Intra-Spin L-PRF. The 4 main families of products present different
      biological signatures and mechanisms, and obvious differences for clinical
      applications. This classification serves as a basis for further investigations of
      the effects of these products. Perspectives of evolutions of this classification
      and terminology are also discussed, particularly concerning the impact of the
      cell content, preservation and activation on these products in sports medicine
      and orthopaedics. 

PMID- 24932441
TI  - PRP treatment effects on degenerative tendinopathy - an in vitro model study.
AB  - Platelet-rich plasma (PRP) has become a popular option for the treatment of
      injured tendons. However, the efficacy of PRP treatment is a matter of heated
      debate in orthopaedics and sports medicine. In this study, we used a cell culture
      model to evaluate the potential effects of PRP treatment on degenerative
      tendinopathy. The in vitro model, which uses the current concept of "diseases-in
      a-dish", consisted of tendon stem/progenitor cells (TSCs) that were derived from
      rabbit tendons and cultured in differentiating media with and without autologous
      platelet-rich clot releasate (PRCR). We found that 10% PRCR treatment of TSCs
      blocked their non-tenogenic differentiation, as evidenced by the marked decrease
      in lipid droplets, proteoglycan accumulation, and calcium deposition on cell
      surfaces. Moreover, the protein markers for non-tenocytes (adiponectin, collagen
      type II, and osteocalcin) were either minimally expressed or greatly reduced.
      However, after TSCs underwent non-tenogenic differentiation by pre-treatment in
      non-tenogenic media for two days, PRCR only slightly reduced adipogenesis and
      osteogenesis of TSCs, although chondrogenesis was markedly suppressed. Finally,
      PRCR treatment after pre-treatment of TSCs in non-tenogenic media for one week
      had little effect on any of the three nontenogenic differentiations of TSCs.
      These findings suggest that the injection of PRP in clinics may not be able to
      effectively reverse the degenerative conditions of late-stage tendinopathy, which
      are characterized by lipid depositions, proteoglycan accumulation, and
      calcification, either alone or in combination. 

PMID- 24932442
TI  - Impact of local anaesthetics and needle calibres used for painless PRP injections
      on platelet functionality.
AB  - The platelet-rich plasma (PRP) is an autologous biotherapy commonly used for its
      healing properties. Once activated, platelets released a real "cocktail" of
      growth factor and cytokines implied in numerous regenerative processes. However
      the impact of medical practices associated to PRP therapeutic use on platelets
      functionality remains poorly known. OBJECTIVES: we evaluated the in vitro effects
      of two commonly used local anesthetics (Xylocaine(*) and Naropin(*)) on PRP
      functionality. We also investigated the quantity and quality of PRP that passed
      through the smallest gauge needle commercialized. MATERIALS AND METHODS: PRP from
      9 healthy volunteers were prepared using our previously described home made
      purification protocol. Platelet aggregation capacity was evaluated by
      aggregometry assays and the growth factor release was determined by ELISA after
      platelet activation. We also evaluated the platelet activation status, reactivity
      and stability of platelets by flow cytometry using the P-selectin expression
      marker. RESULTS: the association of local anaesthetics with PRP injections
      resulted in a significant decrease of platelets functionality, assessed by their
      capacity of aggregating. Local anaesthetics did not interfere with the growth
      factor release. The different needle sizes and calibres tested for PRP injections
      did not influence the platelet functionality. CONCLUSIONS: the use of local
      anaesthetics to prevent pain during PRP injections could compromise the
      therapeutic potential of PRP. These results suggest using carefully local
      anaesthetics or limiting their use as often is possible. To minimize injection
      pain, we recommend using 30 G needles. These data will lead to clinical
      recommendations for painless and controlled PRP injections.

PMID- 24932443
TI  - Vascular Endothelial Growth Factor-111 (VEGF-111) and tendon healing: preliminary
      results in a rat model of tendon injury.
AB  - Tendon lesions are among the most frequent musculoskeletal pathologies. Vascular
      endothelial growth factor (VEGF) is known to regulate angiogenesis. VEGF-111, a
      biologically active and proteolysis-resistant splice variant of this family, was
      recently identified. This study aimed at evaluating whether VEGF-111 could have a
      therapeutic interest in tendon pathologies. Surgical section of one Achilles
      tendon of rats was performed before a local injection of either saline or VEGF
      111. After 5, 15 and 30 days, the Achilles tendons of 10 rats of both groups were
      sampled and submitted to a biomechanical tensile test. The force necessary to
      induce tendon rupture was greater for tendons of the VEGF-111 group (p<0.05)
      while the section areas of the tendons were similar. The mechanical stress was
      similar at 5 and 15 days in the both groups but was improved for the VEGF-111
      group at day 30 (p <0.001). No difference was observed in the mRNA expression of
      collagen III, tenomodulin and MMP-9. In conclusion, we observed that a local
      injection of VEGF-111 improves the early phases of the healing process of rat
      tendons after a surgical section. Further confirmatory experimentations are
      needed to consolidate our results. 

PMID- 24932444
TI  - Sonographic findings during and after Platelet Rich Plasma injections in tendons.
AB  - Platelet rich plasma has been used in the treatment of tendinopathies, but the
      sonographic modifications of tendons have received less attention. In this paper
      we report the results of an ultrasound evaluation, performed during and after
      plasma injection, in patients with tendinopathy. The sonographic abnormalities
      and neovascularization were registered in twenty tendons. Three plasma injections
      (once a week) were performed, and a rehabilitation program was recommended. Pain
      and patients' satisfaction were evaluated. During the injections plasma spread
      along the collagen fibers, and an intratendineous cleft produced by the injected
      volume was observed. At 12 months two tendons regained a normal echotexture,
      while neovessels were absent in seven. The remaining tendons showed less
      abnormalities and neovascularization in comparison with baseline. The clinical
      improvement was earlier and more consistent. The discrepancy between the
      ultrasound and clinical results may be explained by the peculiar modalities of
      tendon healing induced by plasma administration. 

PMID- 24932445
TI  - Can PRP effectively treat injured tendons?
AB  - PRP is widely used to treat tendon and other tissue injuries in orthopaedics and
      sports medicine; however, the efficacy of PRP treatment on injured tendons is
      highly controversial. In this commentary, I reason that there are many PRP- and
      patient-related factors that influence the outcomes of PRP treatment on injured
      tendons. Therefore, more basic science studies are needed to understand the
      mechanism of PRP on injured tendons. Finally, I suggest that better understanding
      of the PRP action mechanism will lead to better use of PRP for the effective
      treatment of tendon injuries in clinics. 

PMID- 24932446
TI  - Learning about PRP using cell-based models.
AB  - Studies using in vitro cell models enable evaluation of the effects of different
      PRP products under very controlled and standardized conditions. Therefore the
      results of such studies build the basis for understanding the variable results of
      clinical studies on the use of PRPs. The main lessons learned through the use of
      in vitro cell models are that many different PRP products exist and researchers
      have to report on component variation within each product. These different
      products may have distinctive effects on the various cells treated in
      musculoskeletal injuries; therefore, some products might be more beneficial in
      certain indication than others. In its utilization in cell models, PRP may
      generate a variety of positive effects on cell proliferation, recovery, and
      inflammatory response. There might also be a benefit to adding PRP to current
      pharmacological therapies (e.g. corticosteroids) to prevent their commonly known
      negative effects on e.g. tendon and cartilage tissue. 

PMID- 24932447
TI  - Mesenchymal stem cell response to growth factor treatment and low oxygen tension
      in 3-dimensional construct environment.
AB  - INTRODUCTION: cell-based tissue engineering strategies using human mesenchymal
      stem cells (hMSCs) may help to augment tendon healing. To further investigate the
      in-vitro behavior of this cell population, we investigated low oxygen culture
      levels, and growth factor supplementation and their effect on expression of
      tendon extracellular proteins and cell proliferation. MATERIALS AND METHODS: bone
      marrow aspirate (BMA) was harvested during arthroscopic rotator cuff repair.
      Characterized hMSCs derived from BMA were incorporated into 3-dimensional tissue
      engineered constructs (TECs). TECs were analyzed by frozen sections with
      immunohistochemistry for cell density, collagen I and collagen III expression.
      RESULTS: growth factor stimulation and low oxygen increased cell density within
      TECs. Low oxygen and addition of growth factors to culture media demonstrated an
      increase in collagen I and III expression, both in ambient oxygen conditions and
      low oxygen conditions. CONCLUSION: low oxygen and TGFbeta3 demonstrated a
      positive effect on cell number, and type I and III collagen expression in 3D
      culture environments.

PMID- 24932449
TI  - Could single nucleotide polymorphisms influence on the efficacy of platelet-rich
      plasma in the treatment of sport injuries?
AB  - Platelet-rich plasma (PRP) is a new powerful biological tool in sports medicine,
      when used to treat tendon, ligament and muscle injuries. PRP is a fraction of
      autologous whole blood containing an increased number of platelets and a wide
      variety of cytokines that can improve and accelerate the healing of various
      tissues. An analysis of the literature shows promising pre-clinical results for
      PRP treatment, but there is a lack of solid clinical proof to support its use in
      sports medicine, and in fact, clinical findings on individual responses to PRP
      treatment are contradictory. These contradictions may be due to interindividual
      differences in the presence of single nucleotide polymorphisms (SNPs) in genes
      related to PRPs and/or their receptors. These SNPs can determine a greater or
      lesser response to this treatment and consequently a shorter or longer recovery
      time. We have focused our attention in the study of genes related to PRP with the
      aim to develope a genetic profile that will identify the individuals and injuries
      most likely to benefit from PRP treatment. 

PMID- 24932448
TI  - Partnership between platelet-rich plasma and mesenchymal stem cells: in vitro
      experience.
AB  - We aim to identify current in vitro research exploring platelet-rich plasma (PRP)
      effects in human Mesenchymal Stem Cells (MSCs) that may encourage or limit the
      clinical application of MSCs along with PRP. After a systematic search, we
      identified 57 in vitro studies, focused on optimization of MSC manufacturing, and
      expanding knowledge about how PRP modifies MSCs behavior for translational
      purposes. Influences of PRP on proliferation, migration, stemness, preservation
      of MSC immune-modulatory properties and appearance of senescence phenotype have
      been explored. Overall PRP stimulates MSC proliferation, preserves MSCs
      multipotency and does not interfere with any lineage differentiation. PRP (as
      platelet lysate or releasate) preserves the immune-privileged potential of MSCs
      and may delay the appearance of the senescent phenotype. Currently there are few
      data linking precise molecules and biological mechanisms. Various gaps of
      knowledge need to be addressed in order to obtain enough useful information for
      translational purposes. 

PMID- 24932450
TI  - Tendon structure, disease, and imaging.
AB  - Tendon imaging plays a critical role in evaluating tendon diseases and injuries
      including mechanical, degenerative, and overuse disease, inflammatory enthesitis,
      as well as partial and full thickness tears. Ultrasound and magnetic resonance
      imaging (MRI), each with unique benefits and limitations, are commonly utilized
      to assist in diagnosing these diseases and conditions. This review delineates
      important structural properties of tendon and biochemical changes occurring in
      tendon pathology. This review also examines commonly injured tendons including
      tendons of the elbow, tendons of the rotator cuff of the shoulder, hip abductor
      tendons, patellar tendons, and the Achilles tendon to help clinicians better
      recognize tendon disease. Finally, this paper introduces several emerging imaging
      techniques including T2 mapping, ultra-short echo time MRI, and sonoelastography
      as ways in which tendon imaging and evaluation may be improved. 

PMID- 24932451
TI  - Frequency of De Quervain's tenosynovitis and its association with SMS texting.
AB  - OBJECTIVE: to assess the frequency of De Quervain's tenosynovitis and its
      association with SMS texting. METHOD: a cross-sectional survey was conducted
      among undergraduate students studying in different physical therapy schools of
      Karachi belonging to both public and private sectors. Sample size was 300
      students which were selected through convenience sampling. Data was collected
      through self-administered questionnaire and severity of the pain was assessed
      through Universal Pain Assessment Tool and De Quervain's tenosynovitis was
      diagnosed through Finkelstein test. Data entry and analysis were done using
      computer software SPSS version 20. Frequency and percentages were taken for
      categorical variable. Chi-square was applied to determine association between
      different variables and Finkelstein test. P value < 0.05 was considered
      significant. RESULTS: male/female ratio was 1:4. Regarding the use of cell
      phones, majority 165 (55%) were using regular cell phones, another 89 (30%) were
      using touch screen and 38 (13%) were using QWERTY key pads. Almost half of the
      students were frequently using cell phones for texting, out of them 132 (44%)
      texted less than 50 messages per day. Another 96 (32%) did texting between 50-100
      texts. Out of 300 students who filled the questionnaire 125 (42%) students were
      experiencing pain in the thumb/wrist. Finkelstein test when done on students
      almost half (n=149) showed positive results. It was noted that as frequency of
      mobile phone usage increased progressively more and more people showed positive
      Finkelstein Test (p value 0.000). CONCLUSION: the result of the study concluded
      that almost half of the students use their mobile phones for texting more than 50
      S.M.S per day and because of their mobile key pads and high speed of texting they
      experienced pain and weakness over the base of the thumb/wrist which shows the De
      Quervain's positive in that students and there is a positive association between
      the thumb pain and frequent text messaging.

PMID- 24932452
TI  - In vitro evaluation of the anti-bacterial effect of two preparations of platelet
      rich plasma compared with cefazolin and whole blood.
AB  - PURPOSE: This study investigates the antibacterial properties of two different
      platelet-rich plasma (PRP) platelet concentration preparations (PRPLP and PRPHP)
      through a time-kill assay. METHODS: Two different PRP preparations - a single
      spin process yielding lower white blood cells and platelet concentration (PRPLP)
      and one yielding high platelet and white blood cell concentration (PRPHP) - were
      obtained from 2 individuals. PRPLP, PRPHP, phosphate buffered saline (PBS), whole
      blood and Cefazolin were added to experimental reaction tubes, each containing a
      single bacterial inoculum of Staphylococcus aureus (S. aureus), Staphylococcus
      epidermidis (S. epi), methicillin-resistant Staphylococcus aureus (MRSA) or
      Propionibacterium acnes (P. acnes). Two dilutions (1:1,000, and 1:10,000) were
      plated in duplicate tubes, along with positive (blood and PBS) and negative
      (Cefazolin) controls and assessed at five time points (0, 1, 4, 8 and 24 hours).
      RESULTS: After centrifugation, platelet count of PRPLP was 386 +/- 65.5 * 103/?L
      and PRPHP was 867 +/- 234.4 * 103/?L. Both PRP products showed a significant
      decrease (p<0.05) in bacterial growth at 8 hours compared to whole blood.
      CONCLUSION: The application of PRPLP and PRPHP showed a significant decrease in
      bacterial growth after 8 hours for S. aureus, S. epi, MRSA and P. acnes compared
      to the whole blood control group. S.epi, MRSA, and P. acnes also showed a
      significant decrease in bacterial growth after 24 hours. Despite differences in
      platelet concentration and WBC concentration, no difference in antibacterial
      activity was seen between the two preparations.

PMID- 24932453
TI  - Description of a standardized rehabilitation program based on sub-maximal
      eccentric following a platelet-rich plasma infiltration for jumper's knee.
AB  - INTRODUCTION: Different series emphasized the necessity of rehabilitation program
      after infiltration of platelet-rich plasma (PRP) in case of tendinopathy.
      However, most of them describe only briefly the reeducation protocol and these
      programs vary. Our aim was to extensively describe a specific standardized
      rehabilitation program. METHODS: After a review of literature of post-PRP
      infiltration protocols, we had developed a standardized rehabilitation protocol.
      This protocol was evaluated by 30 subjects with chronic jumper's knee who. A
      standardised progressive sub-maximal eccentric program supervised by a physical
      therapist for 6 weeks was started 1 week post-infiltration. The patient benefited
      also from electromyostimulation, isometric strengthening and stretching of the
      quadriceps, cycloergometer and cryotherapy. After the supervised program, the
      patient had to make an auto-reeducation added to the reathletisation protocol for
      6 more weeks which was followed by maintenance exercises up to 1 year. The
      assessments were made using a VAS, IKDC and VISA-P scores. RESULTS: The VAS, IKDC
      and VISA-P scores decreased very significantly with time. The compliance to auto
      reeducation was good. CONCLUSIONS: We proposed a simple and efficient protocol
      based on sub-maximal eccentric reeducation to add to PRP infiltrations in case of
      patellar tendinopathy.

PMID- 24932454
TI  - The use of odds ratio in the large population-based studies: Warning to readers.
AB  - When researchers conduct large prospective studies, they provide results
      generating statistical analysis; therefore readers need considerable familiarity
      with descriptive and inferential statistics. If quantitative judgments are based
      on interpreting odds ratios as though they were relative risks, they are unlikely
      to be seriously in error. Because of the calculating method, the OR is often less
      precise than the RR in estimating the strength of an association, and this should
      definitely be kept in mind by anyone who reads and interprets the results of a
      large population based-study. 

PMID- 24932455
TI  - Meniscal sutures with outside-in technique: our experience with a less expensive
      method.

PMID- 24932456
TI  - No difference at two years between all inside transtibial technique and
      traditional transtibial technique in anterior cruciate ligament reconstruction.
AB  - BACKGROUND: one of the most recent technique is the "all inside" anterior
      cruciate ligament (ACL) reconstruction. One of the main characteristic of this
      procedure is the sparing of the tibial cortex. Furthermore, the all-inside
      technique requires only one tendon harvested. PURPOSE: the present study
      describes two year clinical outcomes of the all-inside method for ACL
      reconstruction, and compares them with clinical results of a group of patients
      treated with the traditional transtibial single-bundle ACL reconstruction
      technique using the semitendinosus and gracilis tendons (ST-G). STUDY DESIGN:
      pilot study, using historical controls. METHODS: ACL reconstruction was performed
      on two groups of 20 patients each. The patients in one group underwent the all
      inside transtibial technique with ST tendon alone. The second group underwent ACL
      reconstruction with the traditional transtibial single-bundle procedure using
      quadrupled ST-G tendons. Follow up at 24 months was undertaken using the IKDC,
      VAS pain score, Lysholm and Tegner scales. RESULTS: the VAS pain score for the
      traditional ACL group was 84.6 +/- 12.6; whereas the score for the all-inside
      group was 81.6 +/- 13.1, with no statistically significant differences between
      the two groups. In the traditional ACL reconstruction group the Lysholm scale
      gave a "good results" for 7 patient (35%) and "excellent results" for 13 patients
      (65%) and the all-inside group gave "sufficient results" for 4 patients (20%),
      "good results" for 7 patients (35%) and "excellent results" for 9 patients (45%)
      (n.s.). The median of Tegner score was 6.5 (2-10) for the standard method group
      and 6 (1-9) for the all-inside group (n.s). The IKDC evaluated 50% of patients
      from the standard technique group as class A, and 45% as class B and 5% as class
      C. As regards patients of the all inside technique 55% were class A, 40% class B
      and, here too, just 5% scored as class C. No patients were classed as group D in
      each group. CONCLUSIONS: this study suggests that, in respect to return to sports
      and adequate articular function, there are no differences between the all-inside
      transtibial ACL reconstruction technique and the traditional transtibial ACL
      reconstruction using ST-G. The role of all-inside transtibial ACL reconstruction
      remains dubious. LEVEL OF EVIDENCE: III or Level C according with Oxford Center
      of EBM.

PMID- 24932458
TI  - Profile of metabolic abnormalities seen in patients with type 2 diabetes mellitus
      and their first degree relatives with metabolic syndrome seen in Benin City, Edo
      state Nigeria.
AB  - BACKGROUND: To determine the profile of metabolic abnormalities in T2DM persons
      with metabolic syndrome and their non-diabetic first-degree relatives who also
      had metabolic syndrome in Benin City. METHODOLOGY: This was a cross sectional
      case controlled study in which convenience sampling technique was used to recruit
      106 persons with T2DM, 96 people who are first degree relatives of type 2
      diabetic persons and 96 controls using a interviewer administered questionnaire
      technique. The following were assessed: anthropometric indices, blood pressure,
      serum lipid profile, fasting blood sugar, proteinuria, and microalbuminuria. The
      data obtained were analyzed using the statistical software-Statistical package
      for social sciences [SPSS] version 16. A p-value of less than 0.05 was taken as
      statistically significant. RESULTS: THE MEAN AGE (SD) OF THE STUDY GROUPS WERE:
      persons living with T2DM: 58.6 +/- 11.2 years, control: 57.69 +/- 60.8 years and
      FDR: 57.4 +/- 10.6 years. No significant age and sex differences were observed in
      these groups. There were more females (59.7%) than males (40.3%) with T2DM. The
      prevalence of MS was 13.5%, 16.7%, and 87.1% in the control, FDR and T2DM
      patients respectively. For the T2DM group of subjects, impaired fasting glycaemia
      was the commonest metabolic abnormality followed by microalbuminuria, low HDL
      cholesterol, high LDL cholesterol, hypercholesterolaemia and
      hypertriglyceridaemia in decreasing frequency. For the FDR group, low HDL
      cholesterol was the commonest metabolic abnormality followed by
      hypertriglyceridaemia, impaired fasting glucose, high LDL cholesterol,
      hypertriglyceridaemia and microalbuminuria in decreasing frequency.
      Hypercholesterolemia and low HDL cholesterol were the commonest metabolic
      abnormalities in the control group. CONCLUSION: The prevalence of the MS in
      persons with T2DM in Nigeria appears to be high. Secondly, there is a high
      prevalence of lipid abnormalities in all the study groups.

PMID- 24932457
TI  - Mitochondrial dysfunction in obesity: potential benefit and mechanism of Co
      enzyme Q10 supplementation in metabolic syndrome.
AB  - Co-enzyme Q10 (Co-Q10) is an essential component of the mitochondrial electron
      transport chain. Most cells are sensitive to co-enzyme Q10 (Co-Q10) deficiency.
      This deficiency has been implicated in several clinical disorders such as heart
      failure, hypertension, Parkinson's disease and obesity. The lipid lowering drug
      statin inhibits conversion of HMG-CoA to mevalonate and lowers plasma Co-Q10
      concentrations. However, supplementation with Co-Q10 improves the
      pathophysiological condition of statin therapy. Recent evidence suggests that Co
      Q10 supplementation may be useful for the treatment of obesity, oxidative stress
      and the inflammatory process in metabolic syndrome. The anti-inflammatory
      response and lipid metabolizing effect of Co-Q10 is probably mediated by
      transcriptional regulation of inflammation and lipid metabolism. This paper
      reviews the evidence showing beneficial role of Co-Q10 supplementation and its
      potential mechanism of action on contributing factors of metabolic and
      cardiovascular complications. 

PMID- 24932459
TI  - A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering:
      Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte
      culture.
AB  - The creation of stable hepatocyte cultures using cell-matrix interactions has
      proven difficult in microdevices due to dimensional constraints limiting the
      utility of classic tissue culture techniques that involve the use of hydrogels
      such as the collagen "double gel" or "overlay". To translate the collagen overlay
      technique into microdevices, we modified collagen using succinylation and
      methylation reactions to create polyanionic and polycationic collagen solutions,
      and deposited them layer-by-layer to create ultrathin collagen nanolayers on
      hepatocytes. These ultrathin collagen layers covered hepatocytes in microdevices
      and 1) maintained cell morphology, viability, and polarity, 2) induced bile
      canalicular formation and actin reorganization, and 3) maintained albumin and
      urea secretions and CYP activity similar to those observed in hepatocytes in
      collagen double gel hepatocytes in plate cultures. Beyond the immediate
      applications of this technique to create stable, in vitro microfluidic hepatocyte
      cultures for drug toxicity testing, this technique is generally applicable as a
      thin biomaterial for other 3D microtissues.

PMID- 24932460
TI  - Regulation of Adherens Junctions in Trabecular Meshwork Cells by Rac GTPase and
      their influence on Intraocular Pressure.
AB  - Intercellular adherens junctions and cell-extracellular matrix interactions are
      presumed to influence aqueous humor (AH) drainage via the conventional route,
      however, their direct role in modulation of intraocular pressure (IOP) is not
      well understood. Here, we investigated the role of Rac GTPase signaling in basal
      and growth factor-induced formation of adherens junctions in human trabecular
      meshwork (HTM) cells as compared to human umbilical vascular endothelial cells,
      and evaluated the effects of inhibition of Rac GTPase activity on IOP in rabbits.
      Expression of a constitutively active Rac1 GTPase or treatment with platelet
      derived growth factor (PDGF), a known activator of Rac GTPase, induced formation
      of beta-catenin-based adherens junctions, actin cytoskeletal reorganization and
      membrane ruffle in HTM cells. In contrast, treatment of HTM cells with inhibitors
      of Rac GTPase caused cell-cell separation, a decrease in adherens junctions, and
      reorganization of actin stress fibers to the cell cortical regions and focal
      adhesion to the cell leading edges. Both, constitutively active Rac1 and PDGF
      stimulated generation of Reactive Oxygen Species (ROS) in HTM cells, and ROS were
      found to increase adherens junction formation and transendothelial electrical
      resistance (TEER) in HTM cells. Topical application of Rac GTPase inhibitors
      (EHT1864 and NSC23766), however, only marginally influenced IOP in rabbit eyes.
      Taken together, these data reveal that while Rac GTPase signaling plays a
      significant role in regulation of adherens junctions, ROS production and TEER in
      cells of the AH outflow pathway, Rac inhibitors showed only a marginal influence
      on IOP in live rabbits.

PMID- 24932462
TI  - Infrared spectral histopathology for cancer diagnosis: a novel approach for
      automated pattern recognition of colon adenocarcinoma.
AB  - Histopathology remains the gold standard method for colon cancer diagnosis. Novel
      complementary approaches for molecular level diagnosis of the disease are need of
      the hour. Infrared (IR) imaging could be a promising candidate method as it
      probes the intrinsic chemical bonds present in a tissue, and provides a "spectral
      fingerprint" of the biochemical composition. To this end, IR spectral
      histopathology, which combines IR imaging and data processing techniques, was
      employed on seventy seven paraffinized colon tissue samples (48 tumoral and 29
      non-tumoral) in the form of tissue arrays. To avoid chemical deparaffinization, a
      digital neutralization of the spectral interference of paraffin was implemented.
      Clustering analysis was used to partition the spectra and construct pseudo
      colored images, for assigning spectral clusters to various tissue structures
      (normal epithelium, malignant epithelium, connective tissue etc.). Based on the
      clustering results, linear discriminant analysis was then used to construct a
      stringent prediction model which was applied on samples without a priori
      histopathological information. The predicted spectral images not only revealed
      common features representative of the colonic tissue biochemical make-up, but
      also highlighted additional features like tumor budding and tumor-stroma
      association in a label-free manner. This novel approach of IR spectral imaging on
      paraffinized tissues showed 100% sensitivity and allowed detection and
      differentiation of normal and malignant colonic features based purely on their
      intrinsic biochemical features. This non-destructive methodology combined with
      multivariate statistical image analysis appears as a promising tool for colon
      cancer diagnosis and opens up the way to the concept of numerical spectral
      histopathology. 

PMID- 24932461
TI  - Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in
      Prostate Cancer.
AB  - Androgen deprivation therapy (ADT) resulting in testosterone suppression is
      central to the management of prostate cancer (PC). As PC incidence increases, ADT
      is more frequently prescribed, and for longer periods of time as survival
      improves. Initial approaches to ADT included orchiectomy or oral estrogen
      (diethylstilbestrol [DES]). DES reduces PC-specific mortality, but causes
      substantial cardiovascular (CV) toxicity. Currently, luteinizing hormone
      releasing hormone agonists (LHRHa) are mainly used; they produce low levels of
      both testosterone and estrogen (as estrogen in men results from the aromatization
      of testosterone), and many toxicities including osteoporosis, fractures, hot
      flashes, erectile dysfunction, muscle weakness, increased risk for diabetes,
      changes in body composition, and CV toxicity. An alternative approach is
      parenteral estrogen, it suppresses testosterone, appears to mitigate the CV
      complications of oral estrogen by avoiding first-pass hepatic metabolism, and
      avoids complications caused by estrogen deprivation. Recent research on the
      toxicity of ADT and the rationale for revisiting parenteral estrogen is
      discussed.

PMID- 24932463
TI  - Chlamydial infections of fish: diverse pathogens and emerging causes of disease
      in aquaculture species.
AB  - Chlamydial infections of fish are emerging as an important cause of disease in
      new and established aquaculture industries. To date, epitheliocystis, a skin and
      gill disease associated with infection by these obligate intracellular pathogens,
      has been described in over 90 fish species, including hosts from marine and fresh
      water environments. Aided by advances in molecular detection and typing, recent
      years have seen an explosion in the description of these epitheliocystis-related
      chlamydial pathogens of fish, significantly broadening our knowledge of the
      genetic diversity of the order Chlamydiales. Remarkably, in most cases, it seems
      that each new piscine host studied has revealed the presence of a
      phylogenetically unique and novel chlamydial pathogen, providing researchers with
      a fascinating opportunity to understand the origin, evolution and adaptation of
      their traditional terrestrial chlamydial relatives. Despite the advances in this
      area, much still needs to be learnt about the epidemiology of chlamydial
      infections in fish if these pathogens are to be controlled in farmed
      environments. The lack of in vitro methods for culturing of chlamydial pathogens
      of fish is a major hindrance to this field. This review provides an update on our
      current knowledge of the taxonomy and diversity of chlamydial pathogens of fish,
      discusses the impact of these infections on the health, and highlights further
      areas of research required to understand the biology and epidemiology of this
      important emerging group of fish pathogens of aquaculture species.

PMID- 24932464
TI  - Ian Douglas Ronayne.

PMID- 24932465
TI  - Do implants really help? A look at how implants enhance the quality of life for
      our patients.

PMID- 24932466
TI  - Retraction. Differences between bispectral index and spectral entropy during
      xenon anaesthesia: a comparison with propofol anaesthesia.

PMID- 24932468
TI  - Retraction notice to: Nuclear receptor function requires a TFTC-type histone
      acetyl transferase complex.

PMID- 24932467
TI  - Competition-interaction landscapes for the joint response of forests to climate
      change.
AB  - The recent global increase in forest mortality episodes could not have been
      predicted from current vegetation models that are calibrated to regional climate
      data. Physiological studies show that mortality results from interactions between
      climate and competition at the individual scale. Models of forest response to
      climate do not include interactions because they are hard to estimate and require
      long-term observations on individual trees obtained at frequent (annual)
      intervals. Interactions involve multiple tree responses that can only be
      quantified if these responses are estimated as a joint distribution. A new
      approach provides estimates of climate-competition interactions in two critical
      ways, (i) among individuals, as a joint distribution of responses to combinations
      of inputs, such as resources and climate, and (ii) within individuals, due to
      allocation requirements that control outputs, such as demographic rates.
      Application to 20 years of data from climate and competition gradients shows that
      interactions control forest responses, and their omission from models leads to
      inaccurate predictions. Species most vulnerable to increasing aridity are not
      those that show the largest growth response to precipitation, but rather depend
      on interactions with the local resource environment. This first assessment of
      regional species vulnerability that is based on the scale at which climate
      operates, individual trees competing for carbon and water, supports predictions
      of potential savannification in the southeastern US.

PMID- 24932469
TI  - Retraction notice to: Maturation of microRNA is hormonally regulated by a nuclear
      receptor.

PMID- 24932470
TI  - Retraction notice to: RecA-promoted, RecFOR-independent progressive disassembly
      of replisomes stalled by helicase inactivation.

PMID- 24932471
TI  - Charles Frank Farthing.

PMID- 24932472
TI  - Associations between anxiety, depression, antidepressant medication, obesity and
      weight gain among Canadian women.
AB  - PURPOSE: Some mental illnesses have been suggested to be associated with obesity,
      although results are somewhat inconsistent and research has focused mainly on
      depression. METHODS: Associations between anxiety, depression, medications for
      these illnesses, and obesity were investigated cross-sectionally among women aged
      25-74 (n = 3004) who participated as population controls in a cancer case-control
      study. Participants self-reported information on anxiety, depression, height,
      current weight and weight at age 25. RESULTS: No association was observed between
      either anxiety or depression and either current overweight or obesity status.
      However, depressed women taking antidepressants were more likely to be obese [OR
      = 1.71 (95%CI  =  1.16-2.52) daily antidepressant use; OR = 1.89 (95% CI = 1.21
      2.96) ever tricyclic antidepressant use]. In the full study sample consistent
      positive associations between anxiety, depression and obesity among women with a
      history of antidepressant use, and generally negative associations among women
      without, were suggested. Finally, weight gain was associated with history of
      anxiety [5-19 kg OR = 1.29 (95% CI = 1.06-1.57); >= 20 kg OR = 1.43 (95% CI =
      1.08-1.88)] and depression [>= 20 kg OR = 1.28 (95% CI = 0.99-1.65)].
      CONCLUSIONS: These results suggest depression and anxiety may be associated with
      weight gain and antidepressant use may be associated with obesity.

PMID- 24932473
TI  - Depletion of the aryl hydrocarbon receptor in MDA-MB-231 human breast cancer
      cells altered the expression of genes in key regulatory pathways of cancer.
AB  - The aryl hydrocarbon receptor (AhR), a transcription factor that is best known
      for its role in mediating the toxic responses elicited by poly aromatic
      hydrocarbons as well as many other environmental factors; is also involved in
      breast cancer progression. We previously reported that stable knockdown of AhR
      decreased the tumorigenic properties of the highly metastatic MDA-MB-231 breast
      cancer cell line; whereas ectopic overexpression of AhR was sufficient to
      transform immortalized human mammary epithelial cells to exhibit malignant
      phenotypes. In the present study we investigated the genes that are
      differentially regulated by AhR and are controlling cellular processes linked to
      breast cancer. We used Affymetrix Human GeneChip 1.0-ST whole transcriptome
      arrays to analyze alterations of gene expression resulting from stable AhR
      knockdown in the MDA-MB-231 breast cancer cell line. The expression of 144 genes
      was significantly altered with a >=2.0-fold change and a multiple test corrected
      p-value <=0.05, as a result of AhR knockdown. We demonstrate that AhR knockdown
      alters the expression of several genes known to be linked to cancer. These genes
      include those involved in tryptophan metabolism (KYNU), cell growth (MUC1 and
      IL8), cell survival (BIRC3 and BCL3), cell migration and invasion (S100A4 and
      ABI3), multi-drug resistance (ABCC3) and angiogenesis (VEGFA and CCL2). The
      identification of the genes and pathways affected by AhR depletion provides new
      insight into possible molecular events that could explain the reported phenotypic
      changes. In conclusion AhR knockdown alters the expression of genes known to
      enhance or inhibit cancer progression; tipping the balance towards a state that
      counteracts tumor progression. 

PMID- 24932475
TI  - Anti-biofilm activity: a function of Klebsiella pneumoniae capsular
      polysaccharide.
AB  - Competition and cooperation phenomena occur within highly interactive biofilm
      communities and several non-biocides molecules produced by microorganisms have
      been described as impairing biofilm formation. In this study, we investigated the
      anti-biofilm capacities of an ubiquitous and biofilm producing bacterium,
      Klebsiella pneumoniae. Cell-free supernatant from K. pneumoniae planktonic
      cultures showed anti-biofilm effects on most Gram positive bacteria tested but
      also encompassed some Gram negative bacilli. The anti-biofilm non-bactericidal
      activity was further investigated on Staphylococcus epidermidis, by determining
      the biofilm biomass, microscopic observations and agglutination measurement
      through a magnetic bead-mediated agglutination test. Cell-free extracts from K.
      pneumoniae biofilm (supernatant and acellular matrix) also showed an influence,
      although to a lesser extend. Chemical analyses indicated that the active molecule
      was a high molecular weight polysaccharide composed of five monosaccharides:
      galactose, glucose, rhamnose, glucuronic acid and glucosamine and the main
      following sugar linkage residues [-> 2)-alpha-L-Rhap-(1 ->]; [-> 4)-alpha-L-Rhap
      (1 ->]; [alpha-D-Galp-(1 ->]; [-> 2,3)-alpha-D-Galp-(1 ->]; [-> 3)-beta-D-Galp-(1
      ->] and, [-> 4)-beta-D-GlcAp-(1 ->]. Characterization of this molecule indicated
      that this component was more likely capsular polysaccharide (CPS) and precoating
      of abiotic surfaces with CPS extracts from different serotypes impaired the
      bacteria-surface interactions. Thus the CPS of Klebsiella would exhibit a
      pleiotropic activity during biofilm formation, both stimulating the initial
      adhesion and maturation steps as previously described, but also repelling
      potential competitors.

PMID- 24932476
TI  - Rate and predictors of mucosal healing in patients with inflammatory bowel
      disease treated with anti-TNF-alpha antibodies.
AB  - OBJECTIVE: Mucosal healing (MH) is an important treatment goal in patients with
      inflammatory bowel disease (IBD), but factors predicting MH under medical therapy
      are largely unknown. In this study, we aimed to characterize predictive factors
      for MH in anti-TNF-alpha antibody-treated IBD patients. METHODS: We
      retrospectively analyzed 248 IBD patients (61.3% CD, 38.7% UC) treated with anti
      TNF-alpha antibodies (infliximab and/or adalimumab) for MH, defined as
      macroscopic absence of inflammatory lesions (Mayo endoscopy score 0 or SES-CD
      score 0) in colonoscopies which were analyzed before and after initiation of an
      anti-TNF-alpha antibody treatment. RESULTS: In patients treated with only one
      anti-TNF-alpha antibody ("TNF1 group", n = 202), 56 patients (27.7%) achieved
      complete MH at follow-up colonoscopy (median overall follow-up time: 63 months).
      In a second cohort (n = 46), which comprised patients who were consecutively
      treated with two anti-TNF-alpha antibodies ("TNF2 group"), 13 patients (28.3%)
      achieved complete MH (median overall follow-up time: 64.5 months). Compared to
      patients without MH, CRP values at follow-up colonoscopy were significantly lower
      in patients with MH (TNF1 group: p = 8.35*10-5; TNF2 group: p = 0.002).
      Multivariate analyses confirmed CRP at follow-up colonoscopy as predictor for MH
      in the TNF1 group (p = 0.012). Overall need for surgery was lower in patients
      with MH (TNF1 group: p = 0.01; TNF2 group: p = 0.03). CONCLUSIONS: We identified
      low serum CRP level at follow-up colonoscopy as predictor for MH, while MH was an
      excellent negative predictor for the need for surgery.

PMID- 24932478
TI  - Effect of dehydroepiandrosterone administration in patients with poor ovarian
      response according to the Bologna criteria.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant to
      IVF treatment protocols in poor responders. However, clinical evidence for DHEA
      on improvement of ovarian response and IVF outcome is still limited, the validity
      of the results of the earlier studies, especially the varied inclusion criteria,
      is a subject of debate. Recently, the ESHRE Working Group developed a new
      definition, the Bologna criteria. The aim of the current study was to investigate
      the potential effect of DHEA treatment on in vitro fertilization (IVF) outcome of
      poor ovarian responders that fulfill the Bologna criteria. METHODS: This study
      investigated 386 poor ovarian responders that fulfill the Bologna criteria.
      Patients underwent IVF-ET treatment with the GnRH antagonist protocol. The study
      group contained 189 patients, who received 75 mg of DHEA daily (25 mg three times
      daily) before the IVF cycle. The control group was composed of 197 patients who
      received infertility treatment, but did not receive DHEA. The IVF outcome
      parameters in each group were compared. RESULTS: The study and control groups did
      not show statistically significant differences in terms of patient demographics
      characteristics, mean numbers of oocytes retrieved, mature oocytes, fertilization
      rate, cleavage rate, or embryo availability. While the DHEA group demonstrated
      significantly higher implantation rates (18.7% vs. 10.1%; P<0.01) and ongoing PRs
      (26.7% vs. 15.8%; P<0.05) as compared with the control. CONCLUSIONS: DHEA pre
      treatment does not significantly increase oocyte yield. However, the ongoing PRs
      in this subgroup of women are significantly higher after DHEA administration,
      suggesting that DHEA may increase IVF results by improving oocyte and embryo
      quality.

PMID- 24932477
TI  - Upper girdle imaging in facioscapulohumeral muscular dystrophy.
AB  - BACKGROUND: In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is
      early involved and often difficult to assess only relying on physical
      examination. Our aim was to evaluate the pattern and degree of involvement of
      upper girdle muscles in FSHD compared with other muscle diseases with scapular
      girdle impairment. METHODS: We propose an MRI protocol evaluating neck and upper
      girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45
      patients affected by muscular dystrophies and myopathies with prominent upper
      girdle involvement underwent this protocol. Acquired scans were retrospectively
      analyzed. RESULTS: The trapezius (100% of the patients) and serratus anterior
      (85% of the patients) were the most and earliest affected muscles in FSHD,
      followed by the latissimus dorsi and pectoralis major, whilst spinati and
      subscapularis (involved in less than 4% of the patients) were consistently spared
      even in late disease stages. Asymmetry and hyperintensities on short-tau
      inversion recovery (STIR) sequences were common features, and STIR
      hyperintensities could also be found in muscles not showing signs of fatty
      replacement. The overall involvement appears to be disease-specific in FSHD as it
      significantly differed from that encountered in the other myopathies.
      CONCLUSIONS: The detailed knowledge of single muscle involvement provides useful
      information for correctly evaluating patients' motor function and to set a
      baseline for natural history studies. Upper girdle imaging can also be used as an
      additional tool helpful in supporting the diagnosis of FSHD in unclear
      situations, and may contribute with hints on the currently largely unknown
      molecular pathogenesis of this disease.

PMID- 24932479
TI  - Understanding cultivar-specificity and soil determinants of the cannabis
      microbiome.
AB  - Understanding microbial partnerships with the medicinally and economically
      important crop Cannabis has the potential to affect agricultural practice by
      improving plant fitness and production yield. Furthermore, Cannabis presents an
      interesting model to explore plant-microbiome interactions as it produces
      numerous secondary metabolic compounds. Here we present the first description of
      the endorhiza-, rhizosphere-, and bulk soil-associated microbiome of five
      distinct Cannabis cultivars. Bacterial communities of the endorhiza showed
      significant cultivar-specificity. When controlling cultivar and soil type the
      microbial community structure was significantly different between plant
      cultivars, soil types, and between the endorhiza, rhizosphere and soil. The
      influence of soil type, plant cultivar and sample type differentiation on the
      microbial community structure provides support for a previously published two
      tier selection model, whereby community composition across sample types is
      determined mainly by soil type, while community structure within endorhiza
      samples is determined mainly by host cultivar. 

PMID- 24932480
TI  - Feasibility of rapid discharge after transoral robotic surgery of the oropharynx.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the use of an algorithm for rapid discharge
      after transoral robotic surgery (TORS) and its effect on postoperative
      complications. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective
      analysis of TORS cases from September 2009 to February 2013 was conducted. The
      effect of patient and tumor characteristics on postoperative length of stay (LOS)
      and complications were analyzed. RESULTS: A total of 91 patients were included;
      79 underwent TORS for malignancy and 12 for a benign process. The mean LOS was
      1.51 days (range, 1-5 days) with a median of 1 day. The mean time to initiation
      of oral diet was 1.26 days (range, 1-7 days) with a median of 1 day. Eleven (12%)
      patients experienced one or more complications during their postoperative course.
      Multivariate analysis demonstrated a significant association between patient and
      procedure variables and postoperative complications. TORS base of tongue
      reduction for obstructive sleep apnea (OSA) was associated with a significantly
      greater mean incremental time to initiation of oral diet (1.0 days, 95%
      confidence interval [CI]: 0.4 to 1.7, P < .001). A significantly greater mean
      incremental LOS was observed for patients with advanced comorbidity and a delay
      in initiation of oral diet beyond 24 hours. CONCLUSIONS: Rapid initiation of oral
      diet and rapid discharge home is feasible and not associated with postoperative
      complications. Similarly, the performance of a concurrent neck dissection does
      not contribute to LOS or the development of postoperative complications. Patients
      undergoing TORS for OSA are at greater risk of delay in initiation of oral diet
      and increased LOS. LEVEL OF EVIDENCE: 4

PMID- 24932482
TI  - Stochasticity in Ca2+ increase in spines enables robust and sensitive information
      coding.
AB  - A dendritic spine is a very small structure (~0.1 um3) of a neuron that processes
      input timing information. Why are spines so small? Here, we provide functional
      reasons; the size of spines is optimal for information coding. Spines code input
      timing information by the probability of Ca2+ increases, which makes robust and
      sensitive information coding possible. We created a stochastic simulation model
      of input timing-dependent Ca2+ increases in a cerebellar Purkinje cell's spine.
      Spines used probability coding of Ca2+ increases rather than amplitude coding for
      input timing detection via stochastic facilitation by utilizing the small number
      of molecules in a spine volume, where information per volume appeared optimal.
      Probability coding of Ca2+ increases in a spine volume was more robust against
      input fluctuation and more sensitive to input numbers than amplitude coding of
      Ca2+ increases in a cell volume. Thus, stochasticity is a strategy by which
      neurons robustly and sensitively code information. 

PMID- 24932481
TI  - miRNA-1236 inhibits HIV-1 infection of monocytes by repressing translation of
      cellular factor VprBP.
AB  - Primary monocytes are refractory to HIV-1 infection and become permissive upon
      differentiation into monocyte-derived dendritic cells (MDDCs) or macrophages.
      Multiple mechanisms have been proposed to interpret HIV-1 restriction in
      monocytes. Human cellular miRNAs can modulate HIV-1 infection by targeting either
      conserved regions of the HIV-1 genome or host gene transcripts. We have recently
      reported that the translation of host protein pur-alpha is repressed by abundant
      cellular miRNAs to inhibit HIV-1 infection in monocytes. Here, we report that the
      transcript of another cellular factor, VprBP [Vpr (HIV-1)-binding protein], was
      repressed by cellular miRNA-1236, which contributes to HIV-1 restriction in
      monocytes. Transfection of miR-1236 inhibitors enhanced translation of VprBP in
      monocytes and significantly promoted viral infection; exogenous input of
      synthesized miR-1236 mimics into MDDCs suppressed translation of VprBP, and,
      accordingly, significantly impaired viral infection. Our data emphasize the role
      of miRNA in modulating differentiation-dependent susceptibility of the host cell
      to HIV-1 infection. Understanding the modulation of HIV-1 infection by cellular
      miRNAs may provide key small RNAs or the identification of new important protein
      targets regulated by miRNAs for the development of antiviral strategies. 

PMID- 24932483
TI  - A re-evaluation of the size of the white shark (Carcharodon carcharias)
      population off California, USA.
AB  - White sharks are highly migratory and segregate by sex, age and size. Unlike
      marine mammals, they neither surface to breathe nor frequent haul-out sites,
      hindering generation of abundance data required to estimate population size. A
      recent tag-recapture study used photographic identifications of white sharks at
      two aggregation sites to estimate abundance in "central California" at 219 mature
      and sub-adult individuals. They concluded this represented approximately one-half
      of the total abundance of mature and sub-adult sharks in the entire eastern North
      Pacific Ocean (ENP). This low estimate generated great concern within the
      conservation community, prompting petitions for governmental endangered species
      designations. We critically examine that study and find violations of model
      assumptions that, when considered in total, lead to population underestimates. We
      also use a Bayesian mixture model to demonstrate that the inclusion of transient
      sharks, characteristic of white shark aggregation sites, would substantially
      increase abundance estimates for the adults and sub-adults in the surveyed sub
      population. Using a dataset obtained from the same sampling locations and widely
      accepted demographic methodology, our analysis indicates a minimum all-life
      stages population size of >2000 individuals in the California subpopulation is
      required to account for the number and size range of individual sharks observed
      at the two sampled sites. Even accounting for methodological and conceptual
      biases, an extrapolation of these data to estimate the white shark population
      size throughout the ENP is inappropriate. The true ENP white shark population
      size is likely several-fold greater as both our study and the original published
      estimate exclude non-aggregating sharks and those that independently aggregate at
      other important ENP sites. Accurately estimating the central California and ENP
      white shark population size requires methodologies that account for biases
      introduced by sampling a limited number of sites and that account for all life
      history stages across the species' range of habitats. 

PMID- 24932484
TI  - Nosocomial transmission of C. difficile in English hospitals from patients with
      symptomatic infection.
AB  - BACKGROUND: Recent evidence suggests that less than one-quarter of patients with
      symptomatic nosocomial Clostridium difficile infections (CDI) are linked to other
      in-patients. However, this evidence was limited to one geographic area. We aimed
      to investigate the level of symptomatic CDI transmission in hospitals located
      across England from 2008 to 2012. METHODS: A generalized additive mixed-effects
      Poisson model was fitted to English hospital-surveillance data. After adjusting
      for seasonal fluctuations and between-hospital variation in reported CDI over
      time, possible clustering (transmission between symptomatic in-patients) of CDI
      cases was identified. We hypothesised that a temporal proximity would be
      reflected in the degree of correlation between in-hospital CDI cases per week.
      This correlation was modelled through a latent autoregressive structure of order
      1 (AR(1)). FINDINGS: Forty-six hospitals (33 general, seven specialist, and six
      teaching hospitals) located in all English regions met our criteria. In total,
      12,717 CDI cases were identified; seventy-five per cent of these occurred >48
      hours after admission. There were slight increases in reports during winter
      months. We found a low, but statistically significant, correlation between
      successive weekly CDI case incidences (phi = 0.029, 95%CI: 0.009-0.049). This
      correlation was five times stronger in a subgroup analysis restricted to teaching
      hospitals (phi = 0.104, 95%CI: 0.048-0.159). CONCLUSIONS: The results suggest
      that symptomatic patient-to-patient transmission has been a source of CDI
      acquisition in English hospitals in recent years, and that this might be a more
      important transmission route in teaching hospitals. Nonetheless, the weak
      correlation indicates that, in line with recent evidence, symptomatic cases might
      not be the primary source of nosocomial CDI in England.

PMID- 24932485
TI  - Effect of fungal colonization of wheat grains with Fusarium spp. on food choice,
      weight gain and mortality of meal beetle larvae (Tenebrio molitor).
AB  - Species of Fusarium have significant agro-economical and human health-related
      impact by infecting diverse crop plants and synthesizing diverse mycotoxins.
      Here, we investigated interactions of grain-feeding Tenebrio molitor larvae with
      four grain-colonizing Fusarium species on wheat kernels. Since numerous
      metabolites produced by Fusarium spp. are toxic to insects, we tested the
      hypothesis that the insect senses and avoids Fusarium-colonized grains. We found
      that only kernels colonized with F. avenaceum or Beauveria bassiana (an insect
      pathogenic fungal control) were avoided by the larvae as expected. Kernels
      colonized with F. proliferatum, F. poae or F. culmorum attracted T. molitor
      larvae significantly more than control kernels. The avoidance/preference
      correlated with larval feeding behaviors and weight gain. Interestingly, larvae
      that had consumed F. proliferatum- or F. poae-colonized kernels had similar
      survival rates as control. Larvae fed on F. culmorum-, F. avenaceum- or B.
      bassiana-colonized kernels had elevated mortality rates. HPLC analyses confirmed
      the following mycotoxins produced by the fungal strains on the kernels:
      fumonisins, enniatins and beauvericin by F. proliferatum, enniatins and
      beauvericin by F. poae, enniatins by F. avenaceum, and deoxynivalenol and
      zearalenone by F. culmorum. Our results indicate that T. molitor larvae have the
      ability to sense potential survival threats of kernels colonized with F.
      avenaceum or B. bassiana, but not with F. culmorum. Volatiles potentially along
      with gustatory cues produced by these fungi may represent survival threat signals
      for the larvae resulting in their avoidance. Although F. proliferatum or F. poae
      produced fumonisins, enniatins and beauvericin during kernel colonization, the
      larvae were able to use those kernels as diet without exhibiting increased
      mortality. Consumption of F. avenaceum-colonized kernels, however, increased
      larval mortality; these kernels had higher enniatin levels than F. proliferatum
      or F. poae-colonized ones suggesting that T. molitor can tolerate or metabolize
      those toxins. 

PMID- 24932486
TI  - Reduction of high levels of internal radio-contamination by dietary intervention
      in residents of areas affected by the Fukushima Daiichi nuclear plant disaster: a
      case series.
AB  - Maintaining low levels of chronic internal contamination among residents in
      radiation-contaminated areas after a nuclear disaster is a great public health
      concern. However, the efficacy of reduction measures for individual internal
      contamination remains unknown. To reduce high levels of internal radiation
      exposure in a group of individuals exposed through environmental sources, we
      performed careful dietary intervention with identification of suspected
      contaminated foods, as part of mass voluntary radiation contamination screenings
      and counseling program in Minamisoma Municipal General Hospital and Hirata
      Central Hospital. From a total of 30,622 study participants, only 9 residents
      displayed internal cesium-137 (Cs-137) levels of more than 50 Bq/kg. The median
      level of internal Cs-137 contamination in these residents at the initial
      screening was 4,830 Bq/body (range: 2,130-15,918 Bq/body) and 69.6 Bq/kg (range:
      50.7-216.3 Bq/kg). All these residents with high levels of internal contamination
      consumed homegrown produce without radiation inspection, and often collected
      mushrooms in the wild or cultivated them on bed-logs in their homes. They were
      advised to consume distributed food mainly and to refrain from consuming
      potentially contaminated foods without radiation inspection and local produces
      under shipment restrictions such as mushrooms, mountain vegetables, and meat of
      wild life. A few months after the intervention, re-examination of Cs levels
      revealed remarkable reduction of internal contamination in all residents.
      Although the levels of internal radiation exposure appear to be minimal amongst
      most residents in Fukushima, a subset of the population, who unknowingly consumed
      highly contaminated foodstuffs, experienced high levels of internal
      contamination. There seem to be similarities in dietary preferences amongst
      residents with high internal contamination levels, and intervention based on pre-
      and post-test counseling and dietary advice from medical care providers about
      risky food intake appears to be a feasible option for changing residents' dietary
      practices, subsequently resulting in a reduction in Cs internal contamination
      levels. 

PMID- 24932487
TI  - MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the
      gastrointestinal tract.
AB  - INTRODUCTION: JC virus (JCV), a human polyomavirus that causes progressive
      multifocal leukoencephalopathy (PML), has been linked to colorectal cancer (CRC).
      However, determination of JCV infection and its role in carcinogenesis has been
      challenging, highlighting the need for better diagnostic strategies for this
      virus. JCV-specific microRNAs (miRNAs) were identified and shown to negatively
      regulate oncogenic JCV T-Ag. Herein, we determined the pattern of JCV miRNA
      expression in clinical specimens from healthy subjects and CRC patients. MATERIAL
      AND METHODS: JCV miRNA expression was validated in CRC cell lines transfected
      with the JCV T-Ag. Results were confirmed using CRC tissues that were expressed T
      Ag. Expression of JCV-specific miR-J1-5p was measured in fresh stool samples from
      healthy volunteers, and samples from fecal occult blood test kits from healthy
      subject, and patients with colorectal neoplasms. RESULTS: JCV miR-J1-5p was
      detected in JCV-transfected, but not vector-transfected, CRC cells, and was
      stable between cell passages. MiR-J1-5p was present in all six JCV T-Ag+ CRC
      samples. Surprisingly, JCV miRNA was detectable in all normal tissues, but the
      expression was much lower in CRC tissues. Similarly, miR-J1-5p expression was
      present in all fecal samples, but expression was lower in CRCs compared to
      controls or adenoma patients. CONCLUSION: JC virus-specific miR-J1-5p miRNA is a
      potential biomarker for viral infection, and the lower expression in patients
      with colonic neoplasia highlights its biological role regulating oncogenic T-Ag
      expression in CRC. IMPACT: JCV-specific miRNA is a candidate for the development
      of a non-invasive screening test, as well as therapeutic intervention for JCV
      associated diseases.

PMID- 24932488
TI  - Immobilization of His-tagged recombinant xylanase from Penicillium occitanis on
      nickel-chelate Eupergit C for increasing digestibility of poultry feed.
AB  - Recombinant xylanase 2 from Penicillium occitanis expressed with an His-tag in
      Pichia pastoris, termed PoXyn2, was immobilized on nickel-chelate Eupergit C by
      covalent coupling reaction with a high immobilization yield up to 93.49%.
      Characterization of the immobilized PoXyn2 was further evaluated. The optimum pH
      was not affected by immobilization, but the immobilized PoXyn2 exhibited more
      acidic and large optimum pH range (pH 2.0-4.0) than that of the free PoXyn2 (pH
      3.0). The free PoXyn2 had an optimum temperature of 50  degrees C, whereas that
      of the immobilized enzyme was shifted to 65  degrees C. Immobilization increased
      both pH stability and thermostability when compared with the free enzyme.
      Thermodynamically, increase in enthalpy and free energy change after covalent
      immobilization could be credited to the enhanced stability. Immobilized xylanase
      could be reused for 10 consecutive cycles retaining 60% of its initial activity.
      It was found to be effective in releasing reducing sugar from poultry feed.
      Immobilization on Eupergit C is important due to its mechanical resistance at
      high pH and temperature. Hence, considerable stability and reusability of bound
      enzyme may be advantageous for its industrial application. 

PMID- 24932490
TI  - Novel method for reducing temperature of i-STAT1 analyzer in extreme
      environments.

PMID- 24932489
TI  - Identification of a soybean MOTHER OF FT AND TFL1 homolog involved in regulation
      of seed germination.
AB  - Seed germination is an important event in the life cycle of seed plants, and is
      controlled by complex and coordinated genetic networks. Many genes involved in
      the regulation of this process have been identified in different plant species so
      far. Recent studies in both Arabidopsis and wheat have uncovered a new role of
      MOTHER OF FT AND TFL1 (MFT) in seed germination. Here, we reported a homolog of
      MFT in soybean (GmMFT) which strongly expressed in seeds. Detailed expression
      analysis showed that the mRNA level of GmMFT increased with seed development but
      declined during seed germination. The transcription of GmMFT also responded to
      exogenous application of ABA and GA3. Ectopic expression of GmMFT CDS in
      Arabidopsis moderately inhibited seed germination. All these evidences suggest
      that GmMFT may be a negative regulator of seed germination. 

PMID- 24932491
TI  - Comments on: Laboratory tests for the management of major bleeding complications
      and emergency surgery in patients on long-term treatment with direct oral
      anticoagulants: proposals of the Working Group on Perioperative Haemostasis
      (GIHP): a rebuttal.

PMID- 24932492
TI  - Comments on: Laboratory tests for the management of major bleeding complications
      and emergency surgery in patients on long-term treatment with direct oral
      anticoagulants: proposals of the Working Group on Perioperative Haemostasis
      (GIHP).

PMID- 24932493
TI  - Clinical disease severity of respiratory viral co-infection versus single viral
      infection: a systematic review and meta-analysis.
AB  - BACKGROUND: Results from cohort studies evaluating the severity of respiratory
      viral co-infections are conflicting. We conducted a systematic review and meta
      analysis to assess the clinical severity of viral co-infections as compared to
      single viral respiratory infections. METHODS: We searched electronic databases
      and other sources for studies published up to January 28, 2013. We included
      observational studies on inpatients with respiratory illnesses comparing the
      clinical severity of viral co-infections to single viral infections as detected
      by molecular assays. The primary outcome reflecting clinical disease severity was
      length of hospital stay (LOS). A random-effects model was used to conduct the
      meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were
      included. The overall quality of evidence applying the GRADE approach ranged from
      moderate for oxygen requirements to low for all other outcomes. No significant
      differences in length of hospital stay (LOS) (mean difference (MD) -0.20 days,
      95% CI -0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p =
      0.09) were documented in subjects with viral co-infections compared to those with
      a single viral infection. There was no evidence for differences in effects across
      age subgroups in post hoc analyses with the exception of the higher mortality in
      preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection
      as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04).
      CONCLUSIONS: No differences in clinical disease severity between viral co
      infections and single respiratory infections were documented. The suggested
      increased risk of mortality observed amongst children with viral co-infections
      requires further investigation.

PMID- 24932494
TI  - Low level constraints on dynamic contour path integration.
AB  - Contour integration is a fundamental visual process. The constraints on
      integrating discrete contour elements and the associated neural mechanisms have
      typically been investigated using static contour paths. However, in our dynamic
      natural environment objects and scenes vary over space and time. With the aim of
      investigating the parameters affecting spatiotemporal contour path integration,
      we measured human contrast detection performance of a briefly presented foveal
      target embedded in dynamic collinear stimulus sequences (comprising five short
      'predictor' bars appearing consecutively towards the fovea, followed by the
      'target' bar) in four experiments. The data showed that participants' target
      detection performance was relatively unchanged when individual contour elements
      were separated by up to 2 degrees  spatial gap or 200 ms temporal gap.
      Randomising the luminance contrast or colour of the predictors, on the other
      hand, had similar detrimental effect on grouping dynamic contour path and
      subsequent target detection performance. Randomising the orientation of the
      predictors reduced target detection performance greater than introducing
      misalignment relative to the contour path. The results suggest that the visual
      system integrates dynamic path elements to bias target detection even when the
      continuity of path is disrupted in terms of spatial (2 degrees ), temporal (200
      ms), colour (over 10 colours) and luminance (-25% to 25%) information. We discuss
      how the findings can be largely reconciled within the functioning of V1
      horizontal connections. 

PMID- 24932495
TI  - Guidelines for therapeutic drug monitoring of vancomycin: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Despite the availability of clinical practice
      guidelines (CPGs) for therapeutic drug monitoring (TDM) of vancomycin, vancomycin
      serum concentrations still do not reach therapeutic concentrations in many
      patients. Thus, we sought to systematically review the quality and consistency of
      recommendations for an international cohort of CPGs regarding vancomycin TDM.
      METHODS: PubMed, Embase, guidelines' websites and Google were searched for CPGs
      for vancomycin TDM. Two independent assessors rated the quality of each CPG using
      the Appraisal of Guidelines for Research & Evaluation II (AGREEII) instrument and
      data were independently extracted. RESULTS: Twelve guidelines were evaluated and
      the overall quality of guidelines for vancomycin TDM was moderate. The highest
      score was recorded in the domain of clarity of presentation, and the lowest score
      was recorded in the domain of rigor of development and stakeholder involvement.
      The specific recommendations for vancomycin TDM were moderately consistent and
      guidelines varied in trough concentration monitoring, frequency of TDM, and serum
      concentration targets. CONCLUSION: The overall guideline quality for vancomycin
      TDM was not optimal and effort is needed to improve guideline quality, especially
      in the domain of rigor of development and stakeholder involvement.

PMID- 24932496
TI  - Folate intake and the risk of breast cancer: a dose-response meta-analysis of
      prospective studies.
AB  - BACKGROUND: Previous observational studies regarding the existence of an
      association between folate intake and the risk of breast cancer have been
      inconsistent. This study aimed to summarize the evidence regarding this
      relationship using a dose-response meta-analytic approach. METHODOLOGY AND
      PRINCIPAL FINDINGS: We performed electronic searches of the PubMed, EmBase, and
      Cochrane Library databases to identify studies published through June 2013. Only
      prospective observational studies that reported breast cancer effect estimates
      with 95% confidence intervals (CIs) for more than 2 folate intake categories were
      included. We excluded traditional case-control studies because of possible bias
      from various confounding factors. Overall, we included 14 prospective studies
      that reported data on 677,858 individuals. Folate intake had little effect on the
      breast cancer risk (relative risk (RR) for highest versus lowest category = 0.97;
      95% CI, 0.90-1.05; P = 0.451). Dose-response meta-analysis also suggested that a
      100 ug/day increase in folate intake had no significant effect on the risk of
      breast cancer (RR = 0.99; 95% CI, 0.98-1.01; P = 0.361). Furthermore, we used
      restricted cubic splines to evaluate the nonlinear relationship between folate
      intake and the risk of breast cancer, and discovered a potential J-shaped
      correlation between folate intake and breast cancer risk (P = 0.007) and revealed
      that a daily folate intake of 200-320 ug was associated with a lower breast
      cancer risk; however, the breast cancer risk increased significantly with a daily
      folate intake >400 ug. CONCLUSION/SIGNIFICANCE: Our study revealed that folate
      intake had little or no effect on the risk of breast cancer; moreover, a dose
      response meta-analysis suggested a J-shaped association between folate intake and
      breast cancer.

PMID- 24932498
TI  - Effect of the internet commerce on dispersal modes of invasive alien species.
AB  - The spread of invasive alien plants has considerable environmental and economic
      consequences, and is one of the most challenging ecological problems. The spread
      of invasive alien plant species depends largely on long-distance dispersal, which
      is typically linked with human activity. The increasing domination of the
      internet will have impacts upon almost all components of our lives, including
      potential consequences for the spread of invasive species. To determine whether
      the rise of Internet commerce has any consequences for the spread of invasive
      alien plant species, we studied the sale of thirteen of some of the most harmful
      Europe invasive alien plant species sold as decorative plants from twenty-eight
      large, well known gardening shops in Poland that sold both via the Internet and
      through traditional customer sales. We also analyzed temporal changes in the
      number of invasive plants sold in the largest Polish internet auction portal.
      When sold through the Internet invasive alien plant species were transported
      considerably longer distances than for traditional sales. For internet sales,
      seeds of invasive alien plant species were transported further than were live
      plants saplings; this was not the case for traditional sales. Also, with e
      commerce the shape of distance distribution were flattened with low skewness
      comparing with traditional sale where the distributions were peaked and right
      skewed. Thus, e-commerce created novel modes of long-distance dispersal, while
      traditional sale resembled more natural dispersal modes. Moreover, analysis of
      sale in the biggest Polish internet auction portal showed that the number of
      alien specimens sold via the internet has increased markedly over recent years.
      Therefore internet commerce is likely to increase the rate at which ecological
      communities become homogenized and increase spread of invasive species by
      increasing the rate of long distance dispersal. 

PMID- 24932497
TI  - Stimulatory interactions between human coronary smooth muscle cells and dendritic
      cells.
AB  - Despite inflammatory and immune mechanisms participating to atherogenesis and
      dendritic cells (DCs) driving immune and non-immune tissue injury response, the
      interactions between DCs and vascular smooth muscle cells (VSMCs) possibly
      relevant to vascular pathology including atherogenesis are still unclear. To
      address this issue, immature DCs (iDCs) generated from CD14+ cells isolated from
      healthy donors were matured either with cytokines (mDCs), or co-cultured (ccDCs)
      with human coronary artery VSMCs (CASMCs) using transwell chambers. Co-culture
      induced DC immunophenotypical and functional maturation similar to cytokines, as
      demonstrated by flow cytometry and mixed lymphocyte reaction. In turn, factors
      from mDCs and ccDCs induced CASMC migration. MCP-1 and TNFalpha, secreted from
      DCs, and IL-6 and MCP-1, secreted from CASMCs, were primarily involved. mDCs
      adhesion to CASMCs was enhanced by CASMC pre-treatment with IFNgamma and TNFalpha
      ICAM-1 and VCAM-1 were involved, since the expression of specific mRNAs for these
      molecules increased and adhesion was inhibited by neutralizing antibodies to the
      counter-receptors CD11c and CD18. Adhesion was also inhibited by CASMC pre
      treatment with the HMG-CoA-reductase inhibitor atorvastatin and the PPARgamma
      agonist rosiglitazone, which suggests a further mechanism for the anti
      inflammatory action of these drugs. Adhesion of DCs to VSMCs was shown also in
      vivo in rat carotid 7 to 21 days after crush and incision injury. The findings
      indicate that DCs and VSMCs can interact with reciprocal stimulation, possibly
      leading to perpetuate inflammation and vascular wall remodelling, and that the
      interaction is enhanced by a cytokine-rich inflammatory environment and down
      regulated by HMGCoA-reductase inhibitors and PPARgamma agonists. 

PMID- 24932499
TI  - Child health and access to health care in France: Evidence on the role of family
      income.
AB  - BACKGROUND: Our paper investigates the relationship between family income and
      child health in France. We first examine whether there is a significant
      correlation between family income and child general health, and the evolution of
      this relationship across childhood years. We then study the role of specific
      health problems, access to health care, and supplemental health insurance
      coverage, in the income gradient in general health. We also quantify the role of
      income in child anthropometric measurements. Whenever possible, we compare our
      results for France with those obtained for other developed countries. METHODS:
      Using data on up to approximately 24,000 French children from the Health, Health
      Care and Insurance Surveys, we apply econometric techniques to quantify the
      correlation between household income, child general health, specific health
      problems, anthropometric characteristics, access to health care, and supplemental
      insurance coverage. RESULTS: There is a positive and significant correlation
      between family income and child general health in France. The income gradient in
      child general health is possibly smaller in France than in other developed
      countries. The gradient in general health is explained by the greater prevalence
      of specific health problems for low-income children. In addition, income is
      strongly correlated with anthropometric characteristics. Access to health care,
      and supplemental health insurance coverage are probably not major determinants of
      the gradient in general health. CONCLUSION: The relationship between income and
      health in adulthood has antecedents in childhood. Improving access to health care
      services for children from low-income families may not be enough to decrease
      social health inequalities in childhood.

PMID- 24932500
TI  - Individual and mixture effects of caffeine and sulfamethoxazole on the
      daggerblade grass shrimp Palaemonetes pugio following maternal exposure.
AB  - Pharmaceuticals and personal care products (PPCPs) such as caffeine and
      sulfamethoxazole have been detected in the estuarine environment. The present
      study characterized effects of a maternal exposure of these compounds on the
      development of the daggerblade grass shrimp Palaemonetes pugio from embryo to
      juvenile life stage. Ovigerous females were exposed to either caffeine (20 mg/L),
      sulfamethoxazole (60 mg/L), or a mixture of both (20 mg/L caffeine and 60 mg/L
      sulfamethoxazole). Embryos were then removed from the females and the effects of
      the PPCPs on hatching, metamorphosis, juvenile growth, and overall mortality were
      determined. No significant effect was observed on gravid female survival after 5
      d of exposure to caffeine, sulfamethoxazole, or the mixture; however, development
      of the embryos on the female shrimp was delayed in the mixture. Caffeine and
      sulfamethoxazole in the mixture significantly reduced embryo survival. There was
      a significant effect of caffeine, sulfamethoxazole, and the mixture on embryo
      hatching time. Exposure to sulfamethoxazole alone significantly delayed larval
      metamorphosis. Exposure to caffeine and sulfamethoxazole separately led to
      significantly smaller length of juvenile shrimp. Maternal exposure to caffeine
      and sulfamethoxazole, individually and in mixture, resulted in negative effects
      on P. pugio offspring survival and development; however, the concentrations
      tested in the present study were well above maximum detected field
      concentrations. These results may be incorporated into PPCP risk assessments to
      protect sensitive estuarine ecosystems more effectively.

PMID- 24932502
TI  - Screening for anal cancer precursors: what is the learning curve for high
      resolution anoscopy?

PMID- 24932501
TI  - Effect of anti-Mullerian hormone in culture medium on quality of mouse oocytes
      matured in vitro.
AB  - Anti-mullerian hormone (AMH) is thought to reflect the growth of follicles and
      the ovarian function. However, the role of AMH in culture medium during in vitro
      maturation (IVM) on oocyte quality and subsequent development potential is
      unclear. The objective of this study is to investigate the effect of recombinant
      human AMH (rh-AMH) supplemented into IVM medium on oocyte quality. Cumulus-oocyte
      complexes (COCs) were obtained from ICR mice and cultured in vitro with the
      different concentrations (0-1,000 ng/ml) of rh-AMH. Following 16-18 h of culture,
      quantitative PCR and ELISA were performed to analyze GDF9 and BMP15 mRNA
      expression and protein production from the oocytes. Subsequently, in vitro
      fertilization (IVF) and early embryonic development were employed to further
      evaluate the quality of in vitro matured oocytes. The results showed that AMH was
      only expressed in cumulus cells but not in the oocytes. However, AMH most
      specific receptor, AMHR-II, was expressed in both oocytes and cumulus cells. The
      levels of GDF9 and BMP15 expression and blastocyst formation rate were
      significantly increased (p<0.05) when the IVM medium was supplemented with 100
      ng/ml of rh-AMH. With AdH1-SiRNA/AMH for knocking down of AMH expression during
      IVM significantly reduced (p<0.05) the levels of GDF9 and BMP15 expression and
      blastocysts formation rate. These results suggest that AHM improves oocytes
      quality by up-regulating GDF9 and BMP15 expressions during IVM. 

PMID- 24932503
TI  - [Contraindications to lung transplantation: evolving limits?].
AB  - In France, the higher frequency of pulmonary sample in organ donors and the
      enhancement of surgical and perioperative life support techniques, have increased
      the number procedures and the short term prognosis of lung transplantation (LT).
      In this setting, the classical contraindications of LT need to be reconsidered.
      In this article, some of the classical contraindication of LT are confronted to
      the experience acquired in other solid organ transplantations or from some LT
      centers. Specific situations such as LT in patients with previous cancer, HIV
      infection, viral hepatitis, nutritional disorders, acutely ill LT candidates and
      aging candidates are addressed. Surgical contraindications are not reviewed. 

PMID- 24932505
TI  - [Breast cancer-mimicking tuberculosis with pacchypleurite in male].

PMID- 24932504
TI  - [Childhood tuberculosis].
AB  - Childhood TB is an indication of failing TB control in the community. It allows
      disease persistence in the population. Mortality and morbidity due to TB is high
      in children. Moreover, HIV co-infection and multidrug-resistant diseases are as
      frequent in children as in adults. Infection is more frequent in younger
      children. Disease risk after primary infection is greatest in infants younger
      than 2 years. In case of exposure, evidence of infection can be obtained using
      the tuberculin skin test (TST) or an interferon-gamma assay (IGRA). There is no
      evidence to support the use of IGRA over TST in young children. TB suspicion
      should be confirmed whenever possible, using new available tools, particularly in
      case of pulmonary and lymph node TB. Induced sputum, nasopharyngeal aspiration
      and fine needle aspiration biopsy provide a rapid and definitive diagnosis of
      mycobacterial infection in a large proportion of patients. Analysis of paediatric
      samples revealed higher sensitivity and specificity values of molecular
      techniques in comparison with the ones originated from adults. Children require
      higher drugs dosages than adults. Short courses of steroids are associated with
      TB treatment in case of respiratory distress, bronchoscopic desobstruction is
      proposed for severe airways involvement and antiretroviral therapy is mandatory
      in case of HIV infection. Post-exposure prophylaxis in children is a highly
      effective strategy to reduce the risk of TB disease. The optimal therapy for
      treatment of latent infection with a presumably multidrug-resistant Mycobacterium
      tuberculosis strain is currently not known.

PMID- 24932506
TI  - [Place of bilobectomy in pulmonary oncology and prognostic factors in NSCLC].
AB  - INTRODUCTION: Bilobectomy may be performed for different reasons and lung tumors.
      There are still controversies regarding the results of this procedure. We
      reviewed our experience of bilobectomy to evaluate the particularities of this
      resection. METHODS: The clinical files of patients operated on for lung tumors in
      two French centers between 1980 and 2009 were prospectively recorded and
      retrospectively analyzed. The characteristics, management, pathology, and
      survival after right-sided resections for non-small cell lung cancer (NSCLC) were
      then compared. RESULTS: During the study period, 3280 right-sided resections were
      performed, including 235 bilobectomy (7%), for NSCLC in 192 cases (82%). Lower
      middle lobectomy (LML) represented 60% of bilobectomy, with carcinoid tumors and
      squamous cell carcinoma being more frequent in this group. Upper-middle lobectomy
      (UML) represented 40% of bilobectomy, with less postoperative complications and
      mortality in this group. In N0-NSCLC, the rate of postoperative mortality and 5
      year survival rates after bilobectomy (4.7% and 46.1%, respectively) were
      intermediate between lobectomy (2.7% and 52.6%) and pneumonectomy (9.6% and
      31.7%, P<10(-6) for both comparisons). There was no significant difference in 5
      year survival rates according to the type of bilobectomy and the performance of
      any induction therapy. CONCLUSION: Bilobectomy is associated with acceptable in
      hospital mortality and encouraging 5-year survival rates despite an increased
      incidence of postoperative complications. Approximation in survival of UML and
      pneumonectomy and of LML and lobectomy may be due to differences in histologic
      features with different fissure extension and interlobar node involvement.

PMID- 24932507
TI  - Increases in myocardial workload induced by rapid atrial pacing trigger
      alterations in global metabolism.
AB  - OBJECTIVE: To determine whether increases in cardiac work lead to alterations in
      the plasma metabolome and whether such changes arise from the heart or peripheral
      organs. BACKGROUND: There is growing evidence that the heart influences systemic
      metabolism through endocrine effects and affecting pathways involved in energy
      homeostasis. METHODS: Nineteen patients referred for cardiac catheterization were
      enrolled. Peripheral and selective coronary sinus (CS) blood sampling was
      performed at serial timepoints following the initiation of pacing, and metabolite
      profiling was performed by liquid chromatography-mass spectrometry (LC-MS).
      RESULTS: Pacing-stress resulted in a 225% increase in the median rate.pressure
      product from baseline. Increased myocardial work induced significant changes in
      the peripheral concentration of 43 of 125 metabolites assayed, including large
      changes in purine [adenosine (+99%, p = 0.006), ADP (+42%, p = 0.01), AMP (+79%,
      p = 0.004), GDP (+69%, p = 0.003), GMP (+58%, p = 0.01), IMP (+50%, p = 0.03),
      xanthine (+61%, p = 0.0006)], and several bile acid metabolites. The CS changes
      in metabolites qualitatively mirrored those in the peripheral blood in both
      timing and magnitude, suggesting the heart was not the major source of the
      metabolite release. CONCLUSIONS: Isolated increases in myocardial work can induce
      changes in the plasma metabolome, but these changes do not appear to be directly
      cardiac in origin. A number of these dynamic metabolites have known signaling
      functions. Our study provides additional evidence to a growing body of literature
      on metabolic 'cross-talk' between the heart and other organs.

PMID- 24932508
TI  - Multiplex assay for live-cell monitoring of cellular fates of amyloid-beta
      precursor protein (APP).
AB  - Amyloid-beta precursor protein (APP) plays a central role in pathogenesis of
      Alzheimer's disease. APP has a short half-life and undergoes complex proteolytic
      processing that is highly responsive to various stimuli such as changes in
      cellular lipid or energy homeostasis. Cellular trafficking of APP is controlled
      by its large protein interactome, including dozens of cytosolic adaptor proteins,
      and also by interactions with lipids. Currently, cellular regulation of APP is
      mostly studied based on appearance of APP-derived proteolytic fragments to
      conditioned media and cellular extracts. Here, we have developed a novel live
      cell assay system based on several indirect measures that reflect altered APP
      trafficking and processing in cells. Protein-fragment complementation assay
      technology for detection of APP-BACE1 protein-protein interaction forms the core
      of the new assay. In a multiplex form, the assay can measure four endpoints:
      total cellular APP level, total secreted sAPP level in media, APP-BACE1
      interaction in cells and in exosomes released by the cells. Functional validation
      of the assay with pharmacological and genetic tools revealed distinct patterns of
      cellular fates of APP, with immediate mechanistic implications. This new
      technology will facilitate functional genomics studies of late-onset Alzheimer's
      disease, drug discovery efforts targeting APP and characterization of the
      physiological functions of APP and its proteolytic fragments. 

PMID- 24932509
TI  - Continuous morphological variation correlated with genome size indicates frequent
      introgressive hybridization among Diphasiastrum species (Lycopodiaceae) in
      Central Europe.
AB  - Introgressive hybridization is an important evolutionary process frequently
      contributing to diversification and speciation of angiosperms. Its extent in
      other groups of land plants has only rarely been studied, however. We therefore
      examined the levels of introgression in the genus Diphasiastrum, a taxonomically
      challenging group of Lycopodiophytes, using flow cytometry and numerical and
      geometric morphometric analyses. Patterns of morphological and cytological
      variation were evaluated in an extensive dataset of 561 individuals from 57
      populations of six taxa from Central Europe, the region with the largest known
      taxonomic complexity. In addition, genome size values of 63 individuals from
      Northern Europe were acquired for comparative purposes. Within Central European
      populations, we detected a continuous pattern in both morphological variation and
      genome size (strongly correlated together) suggesting extensive levels of
      interspecific gene flow within this region, including several large hybrid swarm
      populations. The secondary character of habitats of Central European hybrid swarm
      populations suggests that man-made landscape changes might have enhanced
      unnatural contact of species, resulting in extensive hybridization within this
      area. On the contrary, a distinct pattern of genome size variation among
      individuals from other parts of Europe indicates that pure populations prevail
      outside Central Europe. All in all, introgressive hybridization among
      Diphasiastrum species in Central Europe represents a unique case of extensive
      interspecific gene flow among spore producing vascular plants that cause serious
      complications of taxa delimitation. 

PMID- 24932511
TI  - Giant thermoelectric effect in graphene-based topological insulators with heavy
      adatoms and nanopores.
AB  - Designing thermoelectric materials with high figure of merit ZT = S(2)GT/Ktot
      requires fulfilling three often irreconcilable conditions, that is, the high
      electrical conductance G, small thermal conductance Ktot, and high Seebeck
      coefficient S. Nanostructuring is one of the promising ways to achieve this goal
      as it can substantially suppress lattice contribution to Ktot. However, it may
      also unfavorably influence the electronic transport in an uncontrollable way.
      Here, we theoretically demonstrate that this issue can be ideally solved by
      fabricating graphene nanoribbons with heavy adatoms and nanopores. The adatoms
      locally enhance spin-orbit coupling in graphene thereby converting it into a two
      dimensional topological insulator with a band gap in the bulk and robust helical
      edge states, which carry electrical current and generate a highly optimized power
      factor S(2)G per helical conducting channel due to narrow boxcar-function-shaped
      electronic transmission (surpassing even the Mahan-Sofo limit obtained for delta
      function-shaped electronic transmission). Concurrently, the array of nanopores
      impedes the lattice thermal conduction through the bulk. Using quantum transport
      simulations coupled with first-principles electronic and phononic band structure
      calculations, the thermoelectric figure of merit is found to reach its maximum ZT
      ? 3 at low temperatures T ? 40 K. This paves a way to design high-ZT materials by
      exploiting the nontrivial topology of electronic states through nanostructuring. 

PMID- 24932510
TI  - Mining gene expression data of multiple sclerosis.
AB  - OBJECTIVES: Microarray produces a large amount of gene expression data,
      containing various biological implications. The challenge is to detect a panel of
      discriminative genes associated with disease. This study proposed a robust
      classification model for gene selection using gene expression data, and performed
      an analysis to identify disease-related genes using multiple sclerosis as an
      example. MATERIALS AND METHODS: Gene expression profiles based on the
      transcriptome of peripheral blood mononuclear cells from a total of 44 samples
      from 26 multiple sclerosis patients and 18 individuals with other neurological
      diseases (control) were analyzed. Feature selection algorithms including Support
      Vector Machine based on Recursive Feature Elimination, Receiver Operating
      Characteristic Curve, and Boruta algorithms were jointly performed to select
      candidate genes associating with multiple sclerosis. Multiple classification
      models categorized samples into two different groups based on the identified
      genes. Models' performance was evaluated using cross-validation methods, and an
      optimal classifier for gene selection was determined. RESULTS: An overlapping
      feature set was identified consisting of 8 genes that were differentially
      expressed between the two phenotype groups. The genes were significantly
      associated with the pathways of apoptosis and cytokine-cytokine receptor
      interaction. TNFSF10 was significantly associated with multiple sclerosis. A
      Support Vector Machine model was established based on the featured genes and gave
      a practical accuracy of ~86%. This binary classification model also outperformed
      the other models in terms of Sensitivity, Specificity and F1 score. CONCLUSIONS:
      The combined analytical framework integrating feature ranking algorithms and
      Support Vector Machine model could be used for selecting genes for other
      diseases.

PMID- 24932512
TI  - Development of an ultrahigh-performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry method for the simultaneous determination of
      salicylic acid, jasmonic acid, and abscisic acid in rose leaves.
AB  - This paper describes a method to detect and quantitate the endogenous plant
      hormones (+/-)-2-cis-4-trans-abscisic acid, (-)-jasmonic acid, and salicylic acid
      by means of ultrahigh-performance liquid chromatography-tandem mass spectrometry
      (UHPLC-MS/MS) in hybrid rose leaf matrices. Deuterium-labeled [(2)H6] (+)-2-cis-4
      trans-abscisic acid, [(2)H6] (+/-)-jasmonic acid, and [(2)H4]-salicylic acid were
      used as internal standards. Rose samples (10 mg) were extracted with
      methanol/water/acetic acid (10:89:1) and subsequently purified on an Oasis MCX 1
      cm(3) Vac SPE cartridge. Performance characteristics were validated according to
      Commission Decision 2002/657/EC. Recovery, repeatability, and within-laboratory
      reproducibility were acceptable for all phytohormones tested at three different
      concentrations. The decision limit and detection capability for (+/-)-2-cis-4
      trans-abscisic acid, (-)-jasmonic acid, and salicylic acid were 0.0075 and 0.015
      MUg/g, 0.00015 and 0.00030 MUg/g, and 0.0089 and 0.018 MUg/g, respectively.
      Matrix effects (signal suppression or enhancement) appeared to be high for all
      substances considered, implying the need for quantitation based on matrix-matched
      calibration curves. 

PMID- 24932513
TI  - Unravelling the S -> O linkage photoisomerization mechanisms in cis- and trans
      [Ru(bpy)2(DMSO)2](2+) using density functional theory.
AB  - A mechanistic study of the intramolecular S -> O linkage photoisomerization in
      the cis and trans isomers of [Ru(bpy)2(DMSO)2](2+) was performed using density
      functional theory. This study reveals that for the cis isomer the linkage
      photoisomerization of the two DMSO ligands occurs sequentially in the lowest
      triplet excited state and can either be achieved by a one-photon or by a two
      photon mechanism. A mechanistic picture of the S -> O photoisomerization of the
      trans isomer is also proposed. This work especially highlights that both
      adiabatic and nonadiabatic processes are involved in these mechanisms and that
      their coexistence is responsible for the rich photophysics and photochemical
      properties observed experimentally for the studied complexes. The different
      luminescent behavior experimentally observed at low temperature between the cis
      and trans isomers is rationalized based on the peculiarity of the topology of the
      triplet excited-state potential energy surfaces. 

PMID- 24932514
TI  - Robust T1-weighted structural brain imaging and morphometry at 7T using MP2RAGE.
AB  - PURPOSE: To suppress the noise, by sacrificing some of the signal homogeneity for
      numerical stability, in uniform T1 weighted (T1w) images obtained with the
      magnetization prepared 2 rapid gradient echoes sequence (MP2RAGE) and to compare
      the clinical utility of these robust T1w images against the uniform T1w images.
      MATERIALS AND METHODS: 8 healthy subjects (29.0 +/- 4.1 years; 6 Male), who
      provided written consent, underwent two scan sessions within a 24 hour period on
      a 7T head-only scanner. The uniform and robust T1w image volumes were calculated
      inline on the scanner. Two experienced radiologists qualitatively rated the
      images for: general image quality; 7T specific artefacts; and, local structure
      definition. Voxel-based and volume-based morphometry packages were used to
      compare the segmentation quality between the uniform and robust images.
      Statistical differences were evaluated by using a positive sided Wilcoxon rank
      test. RESULTS: The robust image suppresses background noise inside and outside
      the skull. The inhomogeneity introduced was ranked as mild. The robust image was
      significantly ranked higher than the uniform image for both observers (observer
      1/2, p-value = 0.0006/0.0004). In particular, an improved delineation of the
      pituitary gland, cerebellar lobes was observed in the robust versus uniform T1w
      image. The reproducibility of the segmentation results between repeat scans
      improved (p-value = 0.0004) from an average volumetric difference across
      structures of ~ 6.6% to ~ 2.4% for the uniform image and robust T1w image
      respectively. CONCLUSIONS: The robust T1w image enables MP2RAGE to produce,
      clinically familiar T1w images, in addition to T1 maps, which can be readily used
      in uniform morphometry packages.

PMID- 24932515
TI  - Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via
      suppression of inflammation and apoptosis: comparison with celecoxib.
AB  - Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction
      and subfertility. Few studies have addressed the pathogenesis of testicular
      injury in RA and its modulation by effective agents. Thus, the current study
      aimed at evaluating the effects of two testosterone boosting agents; chrysin, a
      natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular
      impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin
      (25 and 50mg/kg) and celecoxib (5mg/kg) were orally administered to Wistar rats
      once daily for 21days starting 1h before arthritis induction. Chrysin suppressed
      paw edema with comparable efficacy to celecoxib. More important, chrysin, dose
      dependently and celecoxib attenuated the testicular injury via reversing lowered
      gonadosomatic index and histopathologic alterations with preservation of
      spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR)
      mRNA expression and serum testosterone with concomitant restoration of LH and
      FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase,
      TNF-alpha and protein expression of COX-2 and iNOS besides elevation of IL-10.
      Alleviation of the testicular impairment was accompanied with suppression of
      oxidative stress via lowering testicular lipid peroxides and nitric oxide. With
      respect to apoptosis, both agents downregulated FasL mRNA expression and caspase
      3 activity in favor of cell survival. For the first time, these findings
      highlight the protective effects of chrysin and celecoxib against testicular
      dysfunction in experimental RA which were mediated via boosting testosterone in
      addition to attenuation of testicular inflammation, oxidative stress and
      apoptosis. Generally, the 50mg/kg dose of chrysin exerted comparable protective
      actions to celecoxib. 

PMID- 24932516
TI  - Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in
      the lung interstitial fibrosis.
AB  - Lung interstitial fibrosis is a chronic lung disease, and few effective therapies
      are available to halt or reverse the progression of the disease. In murine and
      human lung fibrosis, the expression of CD147 is increased. However, the role of
      CD147 in lung fibrosis has not been identified, and it remains to be determined
      whether lung fibrosis would be improved by decreasing the expression of CD147. A
      murine bleomycin-induced lung interstitial fibrosis model was used in the
      experiments, and HAb18 mAbs and CsA were administered during the induction of
      lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the
      collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow
      cytometry analysis showed that M1 macrophages induced higher Th17 differentiation
      than M2 macrophages. After treatment with HAb18 mAbs or after reducing the
      expression of CD147 by lentivirus interference in M1 macrophages, the level of
      Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA
      treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage
      and induced the differentiation of Th17 cells in lung interstitial fibrosis,
      perhaps by regulating some cytokines such as IL-6, IL-1beta, IL-12 and IL-23.
      These results indicated that CD147 may play an important role in the development
      of lung interstitial fibrosis. 

PMID- 24932517
TI  - Native metastable prefibrillar oligomers are the most neurotoxic species among
      amyloid aggregates.
AB  - Many proteins belonging to the amyloid family share the tendency to misfold and
      aggregate following common steps, and display similar neurotoxicity. In the
      aggregation pathway different kinds of species are formed, including several
      types of oligomers and eventually mature fibers. It is now suggested that the
      pathogenic aggregates are not the mature fibrils, but the intermediate, soluble
      oligomers. Many kinds of aggregates have been described to exist in a metastable
      state and in equilibrium with monomers. Up to now it is not clear whether a
      specific structure is at the basis of the neurotoxicity. Here we characterized,
      starting from the early aggregation stages, the oligomer populations formed by an
      amyloid protein, salmon calcitonin (sCT), chosen due to its very slow aggregation
      rate. To prepare different oligomer populations and characterize them by means of
      photoinduced cross-linking SDS-PAGE, Energy Filtered-Transmission Electron
      Microscopy (EF-TEM) and Circular Dichroism (CD) spectroscopy, we used Size
      Exclusion Chromatography (SEC), a technique that does not influence the
      aggregation process leaving the protein in the native state. Taking advantage of
      sCT low aggregation rate, we characterized the neurotoxic potential of the SEC
      separated, non-crosslinked fractions in cultured primary hippocampal neurons,
      analyzing intracellular Ca(2+) influx and apoptotic trend. We provide evidence
      that native, globular, metastable, prefibrillar oligomers (dimers, trimers and
      tetramers) were the toxic species and that low concentrations of these aggregates
      in the population was sufficient to render the sample neurotoxic. Monomers and
      other kind of aggregates, such as annular or linear protofibers and mature
      fibers, were totally biologically inactive. 

PMID- 24932519
TI  - Total laparoscopic radical trachelectomy in the treatment of early-stage cervical
      cancer: review of technique and outcomes.
AB  - PURPOSE OF REVIEW: Fertility preservation in early-stage cervical cancer by total
      laparoscopic radical trachelectomy (TLRT) is gaining acceptance as more cases are
      published in the literature. The objective is to review all the literatures
      regarding TLRT especially over the last 12 months and to describe the technique,
      the operative outcomes, the oncologic outcomes and the obstetric outcomes of this
      procedure. RECENT FINDINGS: As the number of cases reported in the literature
      increases, the effectiveness of TLRT for treating early-stage cervical cancer
      continues to gain support. Under the enhanced vision of the laparoscopy, it is
      easy to preserve the ascending branches of the uterine arteries and to divide the
      ligaments surrounding the cervix and vagina. Since TLRT was first reported, about
      140 cases of TLRT have been reported. The tumour recurrence rate is 2.9%. Fifty
      nine out of 140 patients attempted to conceive after TLRT, and forty-six patients
      succeeded. There were 17 miscarriages, 14 preterm births and 11 term births.
      SUMMARY: TLRT appears well tolerated and effective when performed in centres with
      appropriate experience of laparoscopic techniques. Continued research and
      clinical trials are needed to further elucidate the equivalence or superiority of
      TLRT to conventional methods in terms of obstetric outcome and patients' quality
      of life.

PMID- 24932518
TI  - Divalent cation signaling in immune cells.
AB  - Divalent cations of two alkaline earth metals Ca(2+) and Mg(2+) and the
      transition metal Zn(2+) play vital roles in the immune system, and several immune
      disorders are associated with disturbances of their function. Until recently only
      Ca(2+) was considered to serve as a second messenger. However, signaling roles
      for Mg(2+) and Zn(2+) have been recently described, leading to a reevaluation of
      their role as potential second messengers. We review here the roles of these
      cations as second messengers in light of recent advances in Ca(2+), Mg(2+), and
      Zn(2+) signaling in the immune system. Developing a better understanding of these
      signaling cations may lead to new therapeutic strategies for immune disorders. 

PMID- 24932520
TI  - Gene flow within and between catchments in the threatened riparian plant
      Myricaria germanica.
AB  - One of the major distinctions of riparian habitats is their linearity. In linear
      habitats, gene flow is predicted to follow a one-dimensional stepping stone
      model, characterized by bidirectional gene flow between neighboring populations.
      Here, we studied the genetic structure of Myricaria germanica, a threatened
      riparian shrub which is capable of both wind and water dispersal. Our data led us
      to reject the 'one catchment-one gene pool' hypothesis as we found support for
      two gene pools, rather than four as expected in a study area including four
      catchments. This result also implies that in the history of the studied
      populations, dispersal across catchments has occurred. Two contemporary catchment
      crossing migration events were detected, albeit between spatially proximate
      catchments. Allelic richness and inbreeding coefficients differed substantially
      between gene pools. There was significant isolation by distance, and our data
      confirmed the one-dimensional stepping-stone model of gene flow. Contemporary
      migration was bidirectional within the studied catchments, implying that
      dispersal vectors other than water are important for M. germanica.

PMID- 24932521
TI  - The structure factor of a wormlike chain and the random-phase-approximation
      solution for the spinodal line of a diblock copolymer melt.
AB  - An efficient and convenient numerical approach to calculate the structure factor
      of a wormlike chain model is proposed by directly dealing with a formal solution
      of the Green's function. A precise numerical representation of the structure
      factor of the wormlike chain model is then obtained, for arbitrary chain
      rigidity. On one hand, in the flexible limit, the numerical results recover the
      well-known Debye function of the structure factor of a Gaussian chain and
      furthermore predict the correct large-k behavior that a Gaussian model fails to
      capture; on the other hand, in the rigid limit, the numerical results recover the
      well-known Neugebauer function of the structure factor of a rigid rod. Based on
      the calculated structure factor, the random phase approximation is employed to
      study the physical properties of the order-disorder transition for asymmetric
      wormlike diblock copolymers; particularly, the spinodal line of the disordered
      phase is calculated. For the case of symmetric diblock copolymer microphase
      separation, the present calculation reproduces the phase boundary previously
      determined by self-consistent field theories and yields the entire picture
      crossing over from the flexible-chain limit to the rigid-chain limit. 

PMID- 24932522
TI  - Choosing important health outcomes for comparative effectiveness research: a
      systematic review.
AB  - BACKGROUND: A core outcome set (COS) is a standardised set of outcomes which
      should be measured and reported, as a minimum, in all effectiveness trials for a
      specific health area. This will allow results of studies to be compared,
      contrasted and combined as appropriate, as well as ensuring that all trials
      contribute usable information. The COMET (Core Outcome Measures for Effectiveness
      Trials) Initiative aims to support the development, reporting and adoption of
      COS. Central to this is a publically accessible online resource, populated with
      all available COS. The aim of the review we report here was to identify studies
      that sought to determine which outcomes or domains to measure in all clinical
      trials in a specific condition and to describe the methodological techniques used
      in these studies. METHODS: We developed a multi-faceted search strategy for
      electronic databases (MEDLINE, SCOPUS, and Cochrane Methodology Register). We
      included studies that sought to determine which outcomes/domains to measure in
      all clinical trials in a specific condition. RESULTS: A total of 250 reports
      relating to 198 studies were judged eligible for inclusion in the review. Studies
      covered various areas of health, most commonly cancer, rheumatology, neurology,
      heart and circulation, and dentistry and oral health. A variety of methods have
      been used to develop COS, including semi-structured discussion, unstructured
      group discussion, the Delphi Technique, Consensus Development Conference, surveys
      and Nominal Group Technique. The most common groups involved were clinical
      experts and non-clinical research experts. Thirty-one (16%) studies reported that
      the public had been involved in the process. The geographic locations of
      participants were predominantly North America (n = 164; 83%) and Europe (n = 150;
      76%). CONCLUSIONS: This systematic review identified many health areas where a
      COS has been developed, but also highlights important gaps. It is a further step
      towards a comprehensive, up-to-date database of COS. In addition, it shows the
      need for methodological guidance, including how to engage key stakeholder groups,
      particularly members of the public.

PMID- 24932523
TI  - Impact of Hfq on the Bacillus subtilis transcriptome.
AB  - The RNA chaperone Hfq acts as a central player in post-transcriptional gene
      regulation in several Gram-negative Bacteria, whereas comparatively little is
      known about its role in Gram-positive Bacteria. Here, we studied the function of
      Hfq in Bacillus subtilis, and show that it confers a survival advantage. A
      comparative transcriptome analysis revealed mRNAs with a differential abundance
      that are governed by the ResD-ResE system required for aerobic and anaerobic
      respiration. Expression of resD was found to be up-regulated in the hfq- strain.
      Furthermore, several genes of the GerE and ComK regulons were de-regulated in the
      hfq- background. Surprisingly, only six out of >100 known and predicted small
      RNAs (sRNAs) showed altered abundance in the absence of Hfq. Moreover, Hfq
      positively affected the transcript abundance of genes encoding type I toxin
      antitoxin systems. Taken the moderate effect on sRNA levels and mRNAs together,
      it seems rather unlikely that Hfq plays a central role in RNA transactions in
      Bacillus subtilis. 

PMID- 24932526
TI  - Electron beam controlled restructuring of luminescence centers in polycrystalline
      diamond.
AB  - Color centers in diamond are becoming prime candidates for applications in
      photonics and sensing. In this work we study the time evolution of
      cathodoluminescence (CL) emissions from color centers in a polycrystalline
      diamond film under electron irradiation. We demonstrate room-temperature
      activation of several luminescence centers through a thermal mechanism that is
      catalyzed by an electron beam. CL activation kinetics were measured in realtime
      and are discussed in the context of electron induced dehydrogenation of nitrogen
      vacancy-hydrogen clusters and dislocation defects. Our results also show that
      (unintentional) electron beam induced chemical etching can take place during CL
      analysis of diamond. The etching is caused by residual H2O molecules present in
      high vacuum CL systems. 

PMID- 24932525
TI  - Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic
      outcomes and stronger intestinal barrier.
AB  - Dairy products derived from the milk of cows fed in pastures are characterised by
      higher amounts of conjugated linoleic acid and alpha-linolenic acid (ALA), and
      several studies have shown their ability to reduce cardiovascular risk. However,
      their specific metabolic effects compared with standard dairy in a high-fat diet
      (HFD) context remain largely unknown; this is what we determined in the present
      study with a focus on the metabolic and intestinal parameters. The experimental
      animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture
      dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver,
      white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice,
      despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG
      concentrations, and inflammation in the adipose tissue than the SDC mice.
      Furthermore, they exhibited a higher expression of hepatic PPARalpha mRNA and
      adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative
      activity of the tissues. These results might be explained, in part, by the higher
      amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC
      mice. Moreover, the PDC diet was found to increase the proportions of two
      strategic cell populations involved in the protective function of the intestinal
      epithelium, namely Paneth and goblet cells in the small intestine and colon,
      compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic
      outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due,
      at least in part, to the protective mechanisms induced by specific lipids. 

PMID- 24932524
TI  - Mapped clone and functional analysis of leaf-color gene Ygl7 in a rice hybrid
      (Oryza sativa L. ssp. indica).
AB  - Leaf-color is an effective marker to identify the hybridization of rice. Leaf
      color related genes function in chloroplast development and the photosynthetic
      pigment biosynthesis of higher plants. The ygl7 (yellow-green leaf 7) is a mutant
      with spontaneous yellow-green leaf phenotype across the whole lifespan but with
      no change to its yield traits. We cloned gene Ygl7 (Os03g59640) which encodes a
      magnesium-chelatase ChlD protein. Expression of ygl7 turns green-leaves to
      yellow, whereas RNAi-mediated silence of Ygl7 causes a lethal phenotype of the
      transgenic plants. This indicates the importance of the gene for rice plant. On
      the other hand, it corroborates that ygl7 is a non-null mutants. The content of
      photosynthetic pigment is lower in Ygl7 than the wild type, but its light
      efficiency was comparatively high. All these results indicated that the
      mutational YGL7 protein does not cause a complete loss of original function but
      instead acts as a new protein performing a new function. This new function
      partially includes its preceding function and possesses an additional feature to
      promote photosynthesis. Chl1, Ygl98, and Ygl3 are three alleles of the OsChlD
      gene that have been documented previously. However, mutational sites of OsChlD
      mutant gene and their encoded protein products were different in the three
      mutants. The three mutants have suppressed grain output. In our experiment, plant
      materials of three mutants (ygl7, chl1, and ygl98) all exhibited mutational leaf
      color during the whole growth period. This result was somewhat different from
      previous studies. We used ygl7 as female crossed with chl1 and ygl98,
      respectively. Both the F1 and F2 generation display yellow-green leaf phenotype
      with their chlorophyll and carotenoid content falling between the values of their
      parents. Moreover, we noted an important phenomenon: ygl7-NIL's leaf-color is
      yellow, not yellowy-green, and this is also true of all back-crossed offspring
      with ygl7. 

PMID- 24932527
TI  - Fluorescent monitoring of RNA assembly and processing using the split-spinach
      aptamer.
AB  - As insights into RNA's many diverse cellular roles continue to be gained,
      interest and applications in RNA self-assembly and dynamics remain at the
      forefront of structural biology. The bifurcation of functional molecules into
      nonfunctional fragments provides a useful strategy for controlling and monitoring
      cellular RNA processes and functionalities. Herein we present the bifurcation of
      the preexisting Spinach aptamer and demonstrate its utility as a novel split
      aptamer system for monitoring RNA self-assembly as well as the processing of pre
      short interfering substrates. We show for the first time that the Spinach aptamer
      can be divided into two nonfunctional halves that, once assembled, restore the
      original fluorescent signal characteristic of the unabridged aptamer. In this
      regard, the split-Spinach aptamer is represented as a potential tool for
      monitoring the self-assembly of artificial and/or natural RNAs. 

PMID- 24932528
TI  - Evaluation of a temporal bone prototype by experts in otology.
AB  - BACKGROUND: Inexperienced otologists require training on the temporal bone
      drilling process, prior to any surgical activity. The shortage of cadaveric
      temporal bones exerts pressure to create realistic physical prototypes. This
      paper describes the evaluation by otology experts of a specially developed
      temporal bone resin model. METHODS: Computed tomography images were transformed
      into digital files, and anatomically identical right temporal bone models were
      created using stereolithography. These hand-painted resin prototypes were sent to
      25 otologists, accompanied by a 20-item questionnaire. RESULTS: Satisfaction rate
      was 92 per cent. The overall prototype score was 48.87 out of 60. Average scores
      were: 12.63 out of 15 for anatomy-morphology, 6.98 out of 9 for quality of
      drilling, 16.74 out of 21 for identification of anatomical elements and 7.41 out
      of 9 for stages of drilling. Limitations of the model included an excessively
      vivid facial nerve colour and difficulty in identifying the posterior
      semicircular canal. Disadvantages related to the thickness of the resin and its
      residues were identified. CONCLUSION: The prototype appears to provide an
      attractive solution to the shortage of cadaveric temporal bones. However,
      interest in the model for drilling technique training for inexperienced
      otologists has not yet been assessed.

PMID- 24932530
TI  - Confocal laser endomicroscopy for non-invasive head and neck cancer imaging: a
      comprehensive review.
AB  - Histological assessment is an essential tool in the diagnosis and guidance of the
      treatment of various diseases, in particular cancer, of the head and neck. Recent
      major advances in optical imaging techniques have made it possible to acquire
      high-resolution in vivo images at the cellular scale. Confocal endomicroscopy is
      a non-invasive technique, which can be highly useful whenever meaningful in situ
      histological information is required. The technical aspects of confocal
      endomicroscopy are introduced, followed by an overview of major clinical studies
      in the field of head and neck cancer. Ongoing technical developments,
      contributing to improvements in imaging of the upper aero-digestive tract, are
      also discussed. Finally, the potential complementarities of functional and
      molecular imaging, as compared to morphological endomicroscopy, are highlighted. 

PMID- 24932529
TI  - Detection of human papillomavirus (HPV) in clinical samples: evolving methods and
      strategies for the accurate determination of HPV status of head and neck
      carcinomas.
AB  - Much recent attention has highlighted a subset of head and neck squamous cell
      carcinomas (HNSCCs) related to human papillomavirus (HPV) that has an
      epidemiologic, demographic, molecular and clinical profile which is distinct from
      non-HPV-related HNSCC. The clinical significance of detecting HPV in a HNSCC has
      resulted in a growing expectation for HPV testing of HNSCCs. Although the growing
      demand for routine testing is understandable and appropriate, it has impelled an
      undisciplined approach that has been largely unsystematic. The current state of
      the art has now arrived at a point where a better understanding of HPV-related
      tumorigenesis and a growing experience with HPV testing can now move wide scale,
      indiscriminant and non-standardized testing towards a more directed, clinically
      relevant and standardized approach. This review will address the current state of
      HPV detection; and will focus on why HPV testing is important, when HPV testing
      is appropriate, and how to test for the presence of HPV in various clinical
      samples. As no single test has been universally accepted as a best method, this
      review will consider the strengths and weaknesses of some of the more commonly
      used assays, and will emphasize some emerging techniques that may improve the
      efficiency of HPV testing of clinical samples including cytologic specimens. 

PMID- 24932531
TI  - Species-specific isotope tracers to study the accumulation and biotransformation
      of mixtures of inorganic and methyl mercury by the microalga Chlamydomonas
      reinhardtii.
AB  - The present study demonstrates that species-specific isotope tracing is an useful
      tool to precisely measure Hg accumulation and transformations capabilities of
      living organisms at concentrations naturally encountered in the environment. To
      that end, a phytoplanktonic green alga Chlamydomonas reinhardtii Dangeard
      (Chlamydomonadales, Chlorophyceae) was exposed to mixtures of (199)-isotopically
      enriched inorganic mercury ((199)IHg) and of (201)-isotopically enriched
      monomethylmercury ((201)CH3Hg) at a concentration range between less than 1 pM to
      4 nM. Additionally, one exposure concentration of both mercury species was also
      studied separately to evaluate possible interactive effects. No difference in the
      intracellular contents was observed for algae exposed to (199)IHg and (201)CH3Hg
      alone or in their mixture, suggesting similar accumulation capacity for both
      species at the studied concentrations. Demethylation of (201)CH3Hg was observed
      at the highest exposure concentrations, whereas no methylation was detected. 

PMID- 24932533
TI  - Self-efficacy moderation and mediation roles on BPSD and social support
      influences on subjective caregiver burden in Chinese spouse caregivers of
      dementia patients.
AB  - ABSTRACT Background: This study aims to explore moderation and mediation roles of
      caregiver self-efficacy between subjective caregiver burden and (a) behavioral
      and psychological symptoms (BPSD) of dementia; and (b) social support. Methods: A
      cross-sectional study with 137 spouse caregivers of dementia patients was
      conducted in Shanghai. We collected demographic information for the caregiver
      patient dyads, as well as information associated with dementia-related
      impairments, caregiver social support, caregiver self-efficacy, and SF-36.
      Results: Multiple regression analysis showed that caregiver self-efficacy was a
      moderator both between BPSD and subjective caregiver burden, and social support
      and subjective caregiver burden. Results also showed a partial mediation effect
      of caregiver self-efficacy on the impact of BPSD on subjective caregiver burden,
      and a mediation effect of social support on subjective caregiver burden.
      Caregiver self-efficacy and subjective burden significantly influenced BPSD and
      social support. Conclusion: Caregiver self-efficacy played an important role in
      the paths by which the two factors influenced subjective burden. Enhancing
      caregiver self-efficacy for symptom management (particularly BPSD) can be an
      essential strategy for determining interventions to support dementia caregivers
      in China, and possibly in other countries.

PMID- 24932534
TI  - Amelioration of radiation-induced oral cavity mucositis and distant bone marrow
      suppression in fanconi anemia Fancd2-/- (FVB/N) mice by intraoral GS-nitroxide
      JP4-039.
AB  - The altered DNA damage response pathway in patients with Fanconi anemia (FA) may
      increase the toxicity of clinical radiotherapy. We quantitated oral cavity
      mucositis in irradiated Fanconi anemia Fancd2(-/-) mice, comparing this to
      Fancd2(+/-) and Fancd2(+/+) mice, and we measured distant bone marrow suppression
      and quantitated the effect of the intraoral radioprotector GS-nitroxide, JP4-039
      in F15 emulsion. We found that FA mice were more susceptible to radiation injury
      and that protection from radiation injury by JP4-039/F15 was observed at all
      radiation doses. Adult 10-12-week-old mice, of FVB/N background Fancd2(-/-),
      Fancd2(+/-) and Fancd2(+/+) were head and neck irradiated with 24, 26, 28 or 30
      Gy (large fraction sizes typical of stereotactic radiosurgery treatments) and
      subgroups received intraoral JP4-039 (0.4 mg/mouse in 100 MUL F15 liposome
      emulsion) preirradiation. On day 2 or 5 postirradiation, mice were sacrificed,
      tongue tissue and femur marrow were excised for quantitation of radiation-induced
      stress response, inflammatory and antioxidant gene transcripts, histopathology
      and assay for femur marrow colony-forming hematopoietic progenitor cells. Fancd2(
      /-) mice had a significantly higher percentage of oral mucosal ulceration at day
      5 after 26 Gy irradiation (59.4 +/- 8.2%) compared to control Fancd2(+/+) mice
      (21.7 +/- 2.9%, P = 0.0063). After 24 Gy irradiation, Fancd2(-/-) mice had a
      higher oral cavity percentage of tongue ulceration compared to Fancd2(+/+) mice
      irradiated with higher doses of 26 Gy (P = 0.0123). Baseline and postirradiation
      oral cavity gene transcripts were altered in Fancd2(-/-) mice compared to
      Fancd2(+/+) controls. Fancd2(-/-) mice had decreased baseline femur marrow CFU
      GM, BFUe and CFU-GEMM, which further decreased after 24 or 26 Gy head and neck
      irradiation. These changes were not seen in head- and neck-irradiated Fancd2(+/+)
      mice. In radiosensitive Fancd2(-/-) mice, biomarkers of both local oral cavity
      and distant marrow radiation toxicity were ameliorated by intraoral JP4-039/F15.
      We propose that Fancd2(-/-) mice are a valuable radiosensitive animal model
      system, which can be used to evaluate potential radioprotective agents. 

PMID- 24932536
TI  - Heterogeneity of the internal transcribed spacer region in Leishmania tropica
      isolates from southern Iran.
AB  - Most of cutaneous leishmaniasis cases occur in only 7 countries, including Iran.
      Leishmania tropica is the main cause of anthroponotic cutaneous leishmaniasis in
      Iran. In order to study the heterogeneity and phylogeny of L. tropica in southern
      Iran, a total of 61 isolates were obtained from Bam district and the cities
      Kerman and Shiraz. The internal transcribed spacer (ITS) from the ribosomal DNA
      locus was amplified and then analysed by sequencing. Analysis of the ITS
      sequences showed four haplotypes in the isolates, including 3 haplotypes among
      the 58 isolates from the south eastern region, including Bam district and Kerman
      city, and 2 haplotypes among the 3 isolates from Shiraz city. The results showed
      a monophyletic structure for the south eastern population. In comparison to
      GenBank sequences of L. tropica from different countries, most of the southeast
      Iranian and Indian isolates are comprised in one cluster, while isolates from
      other countries and few other Iranian isolates group in a different cluster.
      Analysis of ITS sequences of south eastern L. tropica showed a homogeneous
      population which could be the basis for other molecular epidemiology studies
      using more discriminative markers and tracing possible changes in the population
      structure of L. tropica. 

PMID- 24932537
TI  - Evidence of inappropriate cardiovascular risk assessment in middle-age women
      based on recommended cut-points for waist circumference.
AB  - BACKGROUND AND AIMS: Diverse waist circumference thresholds for assessment of
      metabolic and cardiovascular risk in Caucasians are recommended by different
      health professional organizations. We aimed to determine optimal sex-specific
      thresholds for anthropometric measures showing the strongest association with
      cardiovascular risk factors in a cohort of middle-aged Germans. METHODS AND
      RESULTS: Statistical analyses are based on data from 426 mothers and 267 fathers
      of participants of the Ulm Birth Cohort Study undergoing a clinical follow-up
      examination in 2008 (median age 41 years) using logistic regression analyses. The
      prevalence of many cardiometabolic risk factors was significantly higher in men
      than in women; hypertension: 45%/17% (p < 0.0001), apolipoprotein ratio B/A1 >
      0.72: 35%/9% (<0.0001), hyperglycemia: 11%/14% (p = 0.3), which is in contrast to
      the predicted cardiovascular risk of 52%/70% and 24%/36% based on thresholds for
      waist circumference proposed by International Diabetes Federation and American
      Heart Association, respectively. We determined optimal thresholds for waist
      circumference between 90 and 95 cm for men and women. Using a threshold of 92 cm
      the prevalence of abdominal obesity was 59% in men and 24% in women, which was in
      agreement with the higher prevalence of overweight and obesity in men than in
      women (Body Mass Index (BMI) > 25: 64%/35%). The prediction of cardiometabolic
      risk factors by waist circumference and waist-to-height ratio did not outperform
      the prediction by BMI. In contrast to BMI, waist circumference was correlated
      with body height independent of sex. CONCLUSION: Currently proposed thresholds
      for waist circumference spuriously overestimate the cardiovascular risk in women,
      but not in men in a German population.

PMID- 24932535
TI  - Association of chromosome translocation rate with low dose occupational radiation
      exposures in U.S. radiologic technologists.
AB  - Chromosome translocations are a well-recognized biological marker of radiation
      exposure and cancer risk. However, there is uncertainty about the lowest dose at
      which excess translocations can be detected, and whether there is temporal decay
      of induced translocations in radiation-exposed populations. Dosimetric
      uncertainties can substantially alter the shape of dose-response relationships;
      although regression-calibration methods have been used in some datasets, these
      have not been applied in radio-occupational studies, where there are also complex
      patterns of shared and unshared errors that these methods do not account for. In
      this article we evaluated the relationship between estimated occupational
      ionizing radiation doses and chromosome translocation rates using fluorescent in
      situ hybridization in 238 U.S. radiologic technologists selected from a large
      cohort. Estimated cumulative red bone marrow doses (mean 29.3 mGy, range 0-135.7
      mGy) were based on available badge-dose measurement data and on questionnaire
      reported work history factors. Dosimetric assessment uncertainties were evaluated
      using regression calibration, Bayesian and Monte Carlo maximum likelihood
      methods, taking account of shared and unshared error and adjusted for
      overdispersion. There was a significant dose response for estimated occupational
      radiation exposure, adjusted for questionnaire-based personal diagnostic
      radiation, age, sex and study group (5.7 translocations per 100 whole genome cell
      equivalents per Gy, 95% CI 0.2, 11.3, P = 0.0440). A significant increasing trend
      with dose continued to be observed for individuals with estimated doses <100 mGy.
      For combined estimated occupational and personal-diagnostic-medical radiation
      exposures, there was a borderline-significant modifying effect of age (P =
      0.0704), but little evidence (P > 0.5) of temporal decay of induced
      translocations. The three methods of analysis to adjust for dose uncertainty gave
      similar results. In summary, chromosome translocation dose-response slopes were
      detectable down to <100 mGy and were compatible with those observed in other
      radiation-exposed populations. However, there are substantial uncertainties in
      both occupational and other (personal-diagnostic-medical) doses that may be
      imperfectly taken into account in our analysis. 

PMID- 24932538
TI  - Ambulatory blood pressure monitoring in the elderly: features and perspectives.
AB  - Aging leads to a multitude of changes in the cardiovascular system that include a
      rise in blood pressure. Age-related changes in blood pressure are mainly
      attributable to an increase in systolic blood pressure, generally associated with
      a slight decrease diastolic blood pressure. This leads to a widening in pulse
      pressure. Ambulatory blood pressure monitoring is a useful tool to understand
      these processes and to refine cardiovascular risk assessment. In the light of
      emerging data in this area, we reviewed the main features of ambulatory blood
      pressure in elderly and discussed the evidence showing that ambulatory blood
      pressure is superior to clinic blood pressure to reflect the true pattern of
      blood pressure over time. Furthermore, we discussed the role of weight control
      obtained by fitness programs to prevent an excessive rise in blood pressure with
      age. A thorough understanding of these concepts is of paramount importance and
      has therapeutic implications in the growing population of elderly subjects with
      increased blood pressure. 

PMID- 24932539
TI  - Liquid chromatography-tandem mass spectrometry analysis of eicosanoids and
      related compounds in cell models.
AB  - Enzyme- and free radical-catalyzed oxidation of polyunsaturated fatty acids
      (PUFAs) produces the eicosanoids, docosanoids and octadecanoids. This large
      family of potent bioactive lipids is involved in many biochemical and signaling
      pathways which are implicated in physiological and pathophysiological processes
      and can be viable therapeutic targets. Liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) offers selectivity, sensitivity, robustness and high
      resolution and is able to analyze a large number of eicosanoids in biological
      samples in a short time. The present article reviews and discusses reported LC
      MS/MS methods and the results obtained from their application in cell models.
      Reliable analytical outcomes are critically important for understanding
      physiological and pathophysiological cellular processes, such as inflammation,
      diseases with inflammatory components (e.g., cardiovascular disease, diabetes,
      metabolic syndrome), as well as cancer. Reported findings obtained by using the
      LC-MS/MS methodology in cell systems may have important predictive as well as
      nutritional and pharmacological implications. We conclude that the LC-MS/MS
      methodology is a versatile and reliable analytical tool for the simultaneous
      analysis of multiple PUFA-derived metabolites including the eicosanoids in cell
      culture samples at concentrations on the pM/nM threshold, i.e. at baseline and
      after stimulation.

PMID- 24932540
TI  - Reprint of: Liquid chromatographic enzymatic studies with on-line Beta-secretase
      immobilized enzyme reactor and 4-(4-dimethylaminophenylazo) benzoic acid/5-[(2
      aminoethyl) amino] naphthalene-1-sulfonic acid peptide as fluorogenic substrate.
AB  - High throughput screening (HTS) techniques are required for the fast hit
      inhibitors selection in the early discovery process. However, in Beta-secretase
      (BACE1) inhibitors screening campaign, the most frequently used methoxycoumarin
      based peptide substrate (M-2420) is not widely applicable when aromatic or
      heterocycle compounds of natural source show auto-fluorescence interferences.
      Here, in order to overcome these drawbacks, we propose the use of a highly
      selective 4-(4-dimethylaminophenylazo)benzoic acid/5-[(2
      aminoethyl)amino]naphthalene-1-sulfonic acid (DABCYL/1,5-EDANS) based peptide
      substrate (Substrate IV), whose cleavage product is devoid of spectroscopic
      interference. HrBACE1-IMER was prepared and characterized in terms of units of
      immobilised hrBACE1. BACE1 catalyzed Substrate IV cleavage was on-line
      kinetically characterized in terms of KM and vmax, in a classical Michaelis and
      Menten study. The on-line kinetic constants were found consistent with those
      obtained with the in solution fluorescence resonance energy transfer (FRET)
      standard method. In order to further validate the use of Substrate IV for
      inhibition studies, the inhibitory potency of the well-known BACE1 peptide
      InhibitorIV (IC50: 0.19 +/- 0.02 MUM) and of the natural compound Uleine (IC50:
      0.57 +/- 0.05) were determined in the optimized on-line hrBACE1-IMER. The IC50
      values on the hrBACE1-IMER system were found in agreement with that obtained by
      the conventional methods confirming the applicability of Substrate IV for on-line
      BACE1 kinetic and inhibition studies.

PMID- 24932541
TI  - Reply on 'Prerequisites for a reliable introduction of in vitro neurotoxicity
      testing within the REACH framework'.

PMID- 24932542
TI  - The PERK-eIF2alpha signaling pathway is involved in TCDD-induced ER stress in
      PC12 cells.
AB  - Studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces
      apoptotic cell death in neuronal cells. However, whether this is the result of
      endoplasmic reticulum (ER) stress-mediated apoptosis remains unknown. In this
      study, we determined whether ER stress plays a role in the TCDD-induced apoptosis
      of pheochromocytoma (PC12) cells and primary neurons. PC12 cells were exposed to
      different TCDD concentrations (1, 10, 100, 200, or 500nM) for varying lengths of
      time (1, 3, 6, 12, or 24h). TCDD concentrations much higher than 10nM (100, 200,
      or 500nM) markedly increased glucose-regulated protein (GRP78) and C/EBP
      homologous protein (CHOP) levels, which are hallmarks of ER stress. We also
      evaluated the effects of TCDD on ER morphology in PC12 cells and primary neurons
      that were treated with different TCDD concentrations (1, 10, 50, or 200nM) for
      24h. Ultrastructural ER alterations were observed with transmission electron
      microscopy in PC12 cells and primary neurons treated with high concentrations of
      TCDD. Furthermore, TCDD-induced ER stress significantly promoted the activation
      of the PKR-like ER kinase (PERK), a sensor for the unfolded protein response
      (UPR), and its downstream target eukaryotic translation initiation factor 2 alpha
      (eIF2alpha); in contrast, TCDD did not appear to affect inositol-requiring enzyme
      1 (IRE1) and activating transcription factor 6 (ATF6), two other UPR sensors.
      Importantly, TCDD significantly inhibited eIF2alpha phosphorylation and triggered
      apoptosis in PC12 cells after 6-24h of treatment. Salubrinal, which activates the
      PERK-eIF2alpha pathway, significantly enhanced eIF2alpha phosphorylation in PC12
      cells and attenuated the TCDD-induced cell death. In contrast, knocking down
      eIF2alpha using small interfering RNA markedly enhanced TCDD-induced cell death.
      Together, these results indicate that the PERK-eIF2alpha pathway plays an
      important role in TCDD-induced ER stress and apoptosis in PC12 cells. 

PMID- 24932543
TI  - Magnetic solid sulfonic acid decorated with hydrophobic regulators: a
      combinatorial and magnetically separable catalyst for the synthesis of alpha
      aminonitriles.
AB  - A three-component, Strecker reaction of a series of aldehydes or ketones, amines,
      and trimethylsilyl cyanide for the synthesis of alpha-aminonitriles in the
      presence of a catalytic amount of a magnetic solid sulfonic acid catalyst,
      Fe3O4@SiO2@Me&Et-PhSO3H under solvent-free conditions have been investigated.
      This catalyst, with a combination of hydrophobicity and acidity on the Fe3O4@SiO2
      core-shell of the magnetic nanobeads, as well as its water-resistant property,
      enabled easy mass transfer and catalytic activity in the Strecker reaction. The
      catalyst was easily separated by an external magnet and the recovered catalyst
      was reused in 6 successive reaction cycles without any significant loss of
      activity. 

PMID- 24932544
TI  - Hydrogen sulfide measurement using sulfide dibimane: critical evaluation with
      electrospray ion trap mass spectrometry.
AB  - Accurate measurement of hydrogen sulfide bioavailability remains a technical
      challenge due to numerous issues involving sample processing, detection methods
      used, and actual biochemical products measured. Our group and others have
      reported that reverse phase HPLC detection of sulfide dibimane (SDB) product from
      the reaction of H2S/HS(-) with monobromobimane allows for analytical detection of
      hydrogen sulfide bioavailability in free and other biochemical forms. However, it
      remains unclear whether possible interfering contaminants may contribute to HPLC
      SDB peak readings that may result in inaccurate measurements of bioavailable
      sulfide. In this study, we critically compared hydrogen sulfide dependent SDB
      detection using reverse phase HPLC (RP-HPLC) versus quantitative SRM electrospray
      ionization mass spectrometry (ESI/MS) to obtain greater clarity into the validity
      of the reverse phase HPLC method for analytical measurement of hydrogen sulfide.
      Using an LCQ-Deca ion-trap mass spectrometer, SDB was identified by ESI/MS
      positive ion mode, and quantified by selected reaction monitoring (SRM) using
      hydrocortisone as an internal standard. Collision induced dissociation (CID)
      parameters were optimized at MS2 level for SDB and hydrocortisone. ESI/MS
      detection of SDB standard was found to be a log order more sensitive than RP-HPLC
      with a lower limit of 0.25 nM. Direct comparison of tissue and plasma SDB levels
      using RP-HPLC and ESI/MS methods revealed comparable sulfide levels in plasma,
      aorta, heart, lung and brain. Together, these data confirm the use of SDB as
      valid indicator of H2S bioavailability and highlights differences between
      analytical detection methods.

PMID- 24932545
TI  - Working with "H2S": facts and apparent artifacts.
AB  - Hydrogen sulfide (H2S) is an important signaling molecule with physiological
      endpoints similar to those of nitric oxide (NO). Growing interest in its
      physiological roles and pharmacological potential has led to large sets of
      contradictory data. The principle cause of these discrepancies can be the common
      neglect of some of the basic H2S chemistry. This study investigates how the
      experimental outcome when working with H2S depends on its source and dose and the
      methodology employed. We show that commercially available NaHS should be avoided
      and that traces of metal ions should be removed because these can reduce
      intramolecular disulfides and change protein structure. Furthermore, high H2S
      concentrations may lead to a complete inhibition of cell respiration,
      mitochondrial membrane potential depolarization and superoxide generation, which
      should be considered when discussing the biological effects observed upon
      treatment with high concentrations of H2S. In addition, we provide chemical
      evidence that H2S can directly react with superoxide. H2S is also capable of
      reducing cytochrome c(3+) with the concomitant formation of superoxide. H2S does
      not directly react with nitrite but with NO electrodes that detect H2S. In
      addition, H2S interferes with the Griess reaction and should therefore be removed
      from the solution by Cd(2+) or Zn(2+) precipitation prior to nitrite
      quantification. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) is
      reduced by H2S, and its use should be avoided in combination with H2S. All these
      constraints must be taken into account when working with H2S to ensure valid
      data. 

PMID- 24932546
TI  - Correlations between brain cortical thickness and cutaneous pain thresholds are
      atypical in adults with migraine.
AB  - BACKGROUND/OBJECTIVE: Migraineurs have atypical pain processing, increased
      expectations for pain, and hypervigilance for pain. Recent studies identified
      correlations between brain structure and pain sensation in healthy adults. The
      objective of this study was to compare cortical thickness-to-pain threshold
      correlations in migraineurs to healthy controls. We hypothesized that migraineurs
      would have aberrant relationships between the anatomical neurocorrelates of pain
      processing and pain thresholds. METHODS: Pain thresholds to cutaneously applied
      heat were determined for 31 adult migraineurs and 32 healthy controls. Cortical
      thickness was determined from magnetic resonance imaging T1-weighted sequences.
      Regional cortical thickness-to-pain threshold correlations were determined for
      migraineurs and controls separately using a general linear model whole brain
      vertex-wise analysis. A pain threshold-by-group interaction analysis was then
      conducted to estimate regions where migraineurs show alterations in the pain
      threshold-to-cortical thickness correlations relative to healthy controls.
      RESULTS: Controls had negative correlations (p<0.01 uncorrected) between pain
      thresholds and cortical thickness in left posterior cingulate/precuneus, right
      superior temporal, right inferior parietal, and left inferior temporal regions,
      and a negative correlation (p<0.01 Monte Carlo corrected) with a left superior
      temporal/inferior parietal region. Migraineurs had positive correlations (p<0.01
      uncorrected) between pain thresholds and cortical thickness in left superior
      temporal/inferior parietal, right precuneus, right superior temporal/inferior
      parietal, and left inferior parietal regions. Cortical thickness-to-pain
      threshold correlations differed between migraine and control groups (p<0.01
      uncorrected) for right superior temporal/inferior parietal, right precentral,
      left posterior cingulate/precuneus, and right inferior parietal regions and
      (p<0.01 Monte Carlo corrected) for a left superior temporal/inferior parietal
      region. CONCLUSIONS: Unlike healthy control subjects who have a significant
      negative correlation between cortical thickness in a superior temporal/inferior
      parietal region with pain thresholds, migraineurs have a non-significant positive
      correlation between cortical thickness in a superior temporal/inferior parietal
      region with pain thresholds. Since this region participates in orienting and
      attention to painful stimuli, absence of the normal correlation might represent a
      migraineurs inability to inhibit pain sensation via shifting attention away from
      the painful stimulus.

PMID- 24932549
TI  - [Testicular tumors - results of primary retroperitoneal lymphadenectomy].

PMID- 24932548
TI  - Carnosine ameliorates lens protein turbidity formations by inhibiting calpain
      proteolysis and ultraviolet C-induced degradation.
AB  - Carnosine (CAR) is an endogenous peptide and present in lens, but there is little
      evidence for its effectiveness in calpain-induced proteolysis inhibition and its
      differential effects toward different wavelengths of ultraviolet (UV)
      irradiation. This study aimed to develop three in vitro cataract models to
      compare the mechanisms underlying the protective activities of CAR. Crude
      crystallins extracted from porcine lenses were used for antiproteolysis assays,
      and purified gamma-crystallins were used for anti-UV assays. The turbidity in
      those in vitro models mimics cataract formation and was assayed by measuring
      optical density (OD) at 405 nm. The effectiveness of CAR on calpain-induced
      proteolysis was studied at 37 and 58  degrees C. Patterns of proteins were then
      analyzed by SDS-PAGE. The turbidity was reduced significantly (p<0.05) at 60 min
      measurements with the increased concentration of CAR (10-300 mM). SDS-PAGE showed
      that the decreased intensities at both ~28 and ~30 kDa protein bands in heat
      enhanced assays were ameliorated by CAR at >=10 mM concentrations. In UV-B
      studies, CAR (200, 300 mM) reduced the turbidity of gamma-crystallin
      significantly (p<0.05) at 6 h observations. The turbidity of samples containing
      gamma-crystallins was ameliorated while incubated with CAR (100, 300 mM)
      significantly (p<0.05) following 4 h of exposure to UV-C. SDS-PAGE showed that
      the presence of CAR reduced UV-B-induced aggregation of gamma-crystallins at ~44
      kDa and resulted in less loss of gamma-crystallin following UV-C exposure. The
      result of modeling also suggests that CAR acts as an inhibitor of calpain. In
      conclusion, CAR protects lens proteins more readily by inhibiting proteolysis and
      UV-C-induced degradation than aggregation induced by UV-B irradiation.

PMID- 24932547
TI  - Active-state model of a dopamine D2 receptor-Galphai complex stabilized by
      aripiprazole-type partial agonists.
AB  - Partial agonists exhibit a submaximal capacity to enhance the coupling of one
      receptor to an intracellular binding partner. Although a multitude of studies
      have reported different ligand-specific conformations for a given receptor,
      little is known about the mechanism by which different receptor conformations are
      connected to the capacity to activate the coupling to G-proteins. We have now
      performed molecular-dynamics simulations employing our recently described active
      state homology model of the dopamine D2 receptor-Galphai protein-complex coupled
      to the partial agonists aripiprazole and FAUC350, in order to understand the
      structural determinants of partial agonism better. We have compared our findings
      with our model of the D2R-Galphai-complex in the presence of the full agonist
      dopamine. The two partial agonists are capable of inducing different
      conformations of important structural motifs, including the extracellular loop
      regions, the binding pocket and, in particular, intracellular G-protein-binding
      domains. As G-protein-coupling to certain intracellular epitopes of the receptor
      is considered the key step of allosterically triggered nucleotide-exchange, it is
      tempting to assume that impaired coupling between the receptor and the G-protein
      caused by distinct ligand-specific conformations is a major determinant of
      partial agonist efficacy. 

PMID- 24932550
TI  - [Urinary bladder carcinoma - research subject recruitment!].

PMID- 24932551
TI  - [Prostate carcinoma - does estrogen administration increase the cardiovascular
      risk?].

PMID- 24932552
TI  - [Recurrent urinary tract infections - prevention without antibiotics].

PMID- 24932553
TI  - [DGU Congress - securing access to care despite the increase in patient numbers].

PMID- 24932554
TI  - [Urolithiasis - settle antiplatelets before ureteroscopy?].

PMID- 24932555
TI  - [Prostate cancer - androgen deprivation: intermittent or continuous?].

PMID- 24932556
TI  - [Imaging - new technique saves unnecessary tissue sampling].

PMID- 24932557
TI  - [Double pump system with rapid irrigation changeover].

PMID- 24932558
TI  - [Taxes explanation: deductions for contract physicians].

PMID- 24932559
TI  - [Discharge against medical advice].

PMID- 24932560
TI  - Local and systemic tolerability of a 2'O-methoxyethyl antisense oligonucleotide
      targeting interleukin-4 receptor-alpha delivery by inhalation in mouse and
      monkey.
AB  - Antisense oligonucleotides (ASOs) bind and facilitate degradation of RNA and
      inhibit protein expression in pathways not easily targeted with small molecules
      or antibodies. Interleukin (IL)-4 and IL-13 potentiate signaling through the
      shared IL-4 receptor-alpha (IL-4Ralpha) subunit of their receptors. ASO targeting
      of IL-4Ralpha mRNA in a mouse model of asthma led to attenuation of airway
      hyperactivity, demonstrating potential benefit in asthma patients. This study
      focused on tolerability of inhaled IL-4Ralpha-targeting ASOs. Toxicity studies
      were performed with mouse- (ISIS 23189) and human-specific (ISIS 369645)
      sequences administered by inhalation. Four week (monkey) or 13 week (mouse)
      repeat doses at levels of up to 15 mg/kg/exposure (exp) and 50 mg/kg/exp,
      respectively, demonstrated dose-dependent effects limited to increases in
      macrophage size and number in lung and tracheobronchial lymph nodes. The changes
      were largely non-specific, reflecting adaptive responses that occur during active
      exposure and deposition of ASO and other material in the lung. Reversibility was
      observed at a rate consistent with the kinetics of tissue clearance of ASO.
      Systemic bioavailability was minimal, and no systemic toxicity was observed at
      exposure levels appreciably above pharmacological doses and doses proposed for
      clinical trials.

PMID- 24932561
TI  - Systemic effects of acute cigarette smoke exposure in mice.
AB  - CONTEXT: Cigarette smoke (CS) causes both pulmonary and extrapulmonary disorders.
      OBJECTIVE: To determine the pulmonary and extrapulmonary effects of acute CS
      exposure in regard to inflammation, oxidative stress and DNA damage. MATERIALS
      AND METHODS: Mice were exposed to CS for 10 days and then their lungs, heart,
      liver, pancreas, kidneys, gastrocnemius muscle and subcutaneous (inguinal and
      flank) and visceral (retroperitoneum and periuterus) adipose tissues were
      excised. Bronchoalveolar lavage fluid samples were obtained for differential cell
      analysis. Inflammatory cell infiltration of the tissues was assessed by
      immunohistochemistry for Mac-3(+) cells, F4/80(+) cells and CD45(+) cells.
      Oxidative stress was determined by immunohistochemistry for thymidine glycol (a
      marker of DNA peroxidation) and 4-hydroxy hexenal (a marker of lipid
      peroxidation), by enzyme-linked immunosorbent assay for protein carbonyls (a
      marker of protein peroxidation) and by measurements of enzyme activities of
      glutathione peroxidase, superoxide dismutase and catalase. DNA double-strand
      breaks were assessed by immunohistochemistry for gammaH2AX. RESULTS: CS exposure
      induced inflammatory cell infiltration, oxidative stress and DNA damage in the
      lung. Neither inflammatory cell infiltration nor DNA damage was observed in any
      extrapulmonary organs. However, oxidative stress was increased in the heart and
      inguinal adipose tissue. DISCUSSIONS: Induction of inflammatory cell infiltration
      and DNA damage by acute CS exposure was confined to the lung. However, an
      increased oxidative burden occurred in the heart and some adipose tissue, as well
      as in the lung. CONCLUSIONS: Although extrapulmonary effects of CS are relatively
      modest compared with the pulmonary effects, some extrapulmonary organs are
      vulnerable to CS-induced oxidative stress.

PMID- 24932562
TI  - Epidemiology and impact of urinary incontinence, overactive bladder, and other
      lower urinary tract symptoms: results of the EPIC survey in Russia, Czech
      Republic, and Turkey.
AB  - OBJECTIVE: To estimate the prevalence of urinary incontinence (UI), overactive
      bladder (OAB), and other lower urinary tract symptoms (LUTS) in the Czech
      Republic, Russia, and Turkey. METHODS: Stage one of this population-based survey
      consisted of computer-assisted telephone interviews to obtain prevalence
      estimates of storage, voiding, and post-micturition LUTS. Stage two face-to-face
      interviews evaluated subjects with mixed urinary incontinence (MUI), stress
      urinary incontinence (SUI) or OAB (case group) and a control group (subjects with
      other incontinence or LUTS complaints, or no symptoms). OUTCOME MEASURE:
      Prevalence of LUTS categories were determined for each country based on
      International Continence Society (ICS) criteria. RESULTS AND LIMITATIONS: A total
      of 3130 individuals agreed to participate in the survey, which found high rates
      of LUTS (men 80%; women 84%) and OAB (men 18%; women 28%). Duration of urinary
      symptoms was relatively brief (approximately 60% <= 3 years) and was associated
      with relatively modest effects on quality of life and work performance in the
      majority of individuals. Forty percent had consulted with a healthcare provider
      about their urinary symptoms, of whom 37% had consulted with a physician and 34%
      with an urologist, and 12% had been treated with a prescription medication. Drug
      therapy, while uncommon, was associated with a high degree of self-reported
      improvement (96%). Because of between-country population differences, aggregate
      results may not always be representative of results for each of the three
      countries individually. Study limitations include reliance on patient self
      report, and potential bias introduced by patients who declined to participate in
      the survey. CONCLUSIONS: The results of this epidemiologic survey found high
      rates of LUTS and OAB, but low levels of medical consultation and very low use of
      medication treatment, despite high levels of improvement when medications were
      used.

PMID- 24932563
TI  - Rapid and reliable DNA assembly via ligase cycling reaction.
AB  - Assembly of DNA parts into DNA constructs is a foundational technology in the
      emerging field of synthetic biology. An efficient DNA assembly method is
      particularly important for high-throughput, automated DNA assembly in
      biofabrication facilities and therefore we investigated one-step, scarless DNA
      assembly via ligase cycling reaction (LCR). LCR assembly uses single-stranded
      bridging oligos complementary to the ends of neighboring DNA parts, a
      thermostable ligase to join DNA backbones, and multiple denaturation-annealing
      ligation temperature cycles to assemble complex DNA constructs. The efficiency of
      LCR assembly was improved ca. 4-fold using designed optimization experiments and
      response surface methodology. Under these optimized conditions, LCR enabled one
      step assembly of up to 20 DNA parts and up to 20 kb DNA constructs with very few
      single-nucleotide polymorphisms (<1 per 25 kb) and insertions/deletions (<1 per
      50 kb). Experimental comparison of various sequence-independent DNA assembly
      methods showed that circular polymerase extension cloning (CPEC) and Gibson
      isothermal assembly did not enable assembly of more than four DNA parts with more
      than 50% of clones being correct. Yeast homologous recombination and LCR both
      enabled reliable assembly of up to 12 DNA parts with 60-100% of individual clones
      being correct, but LCR assembly provides a much faster and easier workflow than
      yeast homologous recombination. LCR combines reliable assembly of many DNA parts
      via a cheap, rapid, and convenient workflow and thereby outperforms existing DNA
      assembly methods. LCR assembly is expected to become the method of choice for
      both manual and automated high-throughput assembly of DNA parts into DNA
      constructs. 

PMID- 24932564
TI  - Fluorescence investigation of the detachment of aluminum phthalocyanine molecules
      from aluminum phthalocyanine nanoparticles in monocytes/macrophages and skin
      cells and their localization in monocytes/macrophages.
AB  - BACKGROUND: Nanoparticles made from aluminum phthalocyanine (AlPc) are non
      fluorescent in the nanoparticle form. Once AlPc molecules become detached from
      the particle, fluorescence occurs. Preliminary work showed the benefit of using
      aluminum phthalocyanine nanoparticles (nAlPc) for the rating of the rejection
      risk of skin autografts in mice by measuring fluorescence intensities of detached
      AlPc. Skin autografts showing a high fluorescence intensity were finally rejected
      suggesting an inflammatory process. In contrast, autografts with normal
      autofluorescence were accepted. This work was focused on the mechanism of this
      finding. The aim is detecting inflammatory processes and the potential use of
      nAlPc for PDT as a new treatment modality. METHODS: The effect of the
      lipopolysaccharide-stimulated monocyte/macrophage murine cell line J774A.1 on the
      monomerization of internalized nAlPc was tested. Further, we investigated the
      influence of J774A.1 cells and the normal skin cell lines L-929 or HaCaT on the
      dissolution of nAlPc by laser scanning microscopy and flow cytometry.
      Localization of AlPc molecules after uptake and dissolution of nanoparticles by
      the cells was surveyed. RESULTS: In co-culture models composed of J774A.1 and
      HaCaT/L-929 cells, the AlPc fluorescence intensity in J774A.1 cells is 1.38/1.89
      fold higher, respectively. According to localization measurements in J774A.1
      cells it can be assumed that nAlPc is taken up via endocytosis and remains in
      endosomes and/or lysosomes dissolving there. Detached molecules of AlPc cause
      rapture of the endosomal and/or lysosomal membrane after irradiation to become
      quite uniformly distributed in the cytoplasm. CONCLUSIONS: Evidence for
      monocytes/macrophages being the origin of the measured AlPc fluorescence in
      rejected skin autografts was confirmed.

PMID- 24932566
TI  - Time-series panel analysis (TSPA): multivariate modeling of temporal associations
      in psychotherapy process.
AB  - OBJECTIVE: Processes occurring in the course of psychotherapy are characterized
      by the simple fact that they unfold in time and that the multiple factors engaged
      in change processes vary highly between individuals (idiographic phenomena).
      Previous research, however, has neglected the temporal perspective by its
      traditional focus on static phenomena, which were mainly assessed at the group
      level (nomothetic phenomena). To support a temporal approach, the authors
      introduce time-series panel analysis (TSPA), a statistical methodology explicitly
      focusing on the quantification of temporal, session-to-session aspects of change
      in psychotherapy. TSPA-models are initially built at the level of individuals and
      are subsequently aggregated at the group level, thus allowing the exploration of
      prototypical models. METHOD: TSPA is based on vector auto-regression (VAR), an
      extension of univariate auto-regression models to multivariate time-series data.
      The application of TSPA is demonstrated in a sample of 87 outpatient
      psychotherapy patients who were monitored by postsession questionnaires.
      Prototypical mechanisms of change were derived from the aggregation of individual
      multivariate models of psychotherapy process. In a 2nd step, the associations
      between mechanisms of change (TSPA) and pre- to postsymptom change were explored.
      RESULTS: TSPA allowed a prototypical process pattern to be identified, where
      patient's alliance and self-efficacy were linked by a temporal feedback-loop.
      Furthermore, therapist's stability over time in both mastery and clarification
      interventions was positively associated with better outcomes. CONCLUSIONS: TSPA
      is a statistical tool that sheds new light on temporal mechanisms of change.
      Through this approach, clinicians may gain insight into prototypical patterns of
      change in psychotherapy.

PMID- 24932565
TI  - The Marriage Checkup: a randomized controlled trial of annual relationship health
      checkups.
AB  - OBJECTIVE: This study assessed the efficacy of the Marriage Checkup (MC) for
      improving relationship health and intimacy. METHOD: Cohabiting married couples (N
      = 215, Mage women = 44.5 years, men = 47 years, 93.1% Caucasian) recruited from a
      northeastern U.S. metropolitan area through print and electronic media were
      randomly assigned to MC treatment or wait-list control. Treatment but not control
      couples participated in assessment and feedback visits, at the beginning of the
      study and again 1 year later. All couples completed 9 sets of questionnaires over
      2 years. Outcome measures included the Quality of Marriage Index, the Global
      Distress subscale of the Marital Satisfaction Inventory-Revised, the Intimate
      Safety Questionnaire, and the Relational Acceptance Questionnaire. RESULTS: A
      latent growth curve model indicated significant between-group differences in
      intimacy at every measurement point after baseline (d ranged from .20 to .55, Md
      = .37), significant between-group differences in women's felt acceptance for
      every measurement point after baseline (d ranged from .17 to .47, Md = .34),
      significant between-group differences in men's felt acceptance through the 1-year
      2-week follow-up (d across follow-up ranged from .11 to .40, Md = .25), and
      significant between-group differences in relationship distress through 1-year 6
      month follow-up (d across follow-up ranged from .11 to .39, Md = .23).
      CONCLUSIONS: Longitudinal analysis of the MC supports the hypothesis that the MC
      significantly improves intimacy, acceptance, and satisfaction. Implications for
      dissemination are discussed.

PMID- 24932568
TI  - Survivors Perceptions of Recovery following Air Medical Transport Accidents.
AB  - Abstract Objective: Air medical transport (AMT) teams play an essential role in
      the care of the critically ill and injured. Their work, however, is not without
      risk. Since the inception of the industry numerous AMT accidents have been
      reported. The objective of this research is to gain a better understanding of the
      post-accident sequelae for professionals who have survived AMT accidents. The
      hope is that this understanding will empower the industry to better support
      survivors and plan for the contingencies of post-accident recovery. Methods:
      Qualitative methods were used to explore the experience of flight crew members
      who have survived an AMT accident. "Accident" was defined using criteria
      established by the National Transportation Safety Board. Traditional focus group
      methodology explored the survivors' experiences following the accident. Results:
      Seven survivors participated in the focus group. Content analysis revealed themes
      in four major domains that described the experience of survivors: Physical,
      Psychological, Relational and Financial. Across the themes survivors reported
      that industry and company response varied greatly, ranging from generous support,
      understanding and action to make safety improvements, to little response or
      action and lack of attention to survivor needs. Conclusion: Planning for AMT post
      accident response was identified to be lacking in scope and quality. More focused
      efforts are needed to assist and support the survivors as they regain both their
      personal and professional lives following the accident. This planning should
      include all stakeholders in safe transport; the individual crewmember, air
      medical transport companies, and the industry at large.

PMID- 24932567
TI  - Predictors of child weight loss and maintenance among family-based treatment
      completers.
AB  - OBJECTIVE: To examine general and treatment-specific predictors of children's
      weight outcomes during a pediatric weight management trial. METHOD: One hundred
      fifty overweight children-69.3% female; M body mass index (BMI) z score (z-BMI) =
      2.21 +/- 0.30-completed family-based behavioral weight loss treatment (FBT),
      followed by randomization to social facilitation maintenance (SFM) treatment
      addressing social support and body image; behavioral skills maintenance treatment
      (BSM), which extended FBT skills to maintenance; or a control condition with no
      maintenance treatment. Regression and mixed-effects repeated-measures analysis of
      covariance (ANCOVA) examined child and parent anthropometric, demographic, and
      psychosocial variables in predicting relative weight outcomes over short- and
      long-term follow-ups. RESULTS: Among FBT completers, lower child baseline z-BMI
      and age, and greater parent BMI reductions during FBT and baseline self-efficacy,
      predicted better child relative weight loss following FBT, F(6, 137) = 7.77, p <
      .001. Higher child-reported post-FBT eating pathology predicted greater relative
      weight loss in SFM than BSM or control from post-FBT to 2-year follow-up,
      F(4,255.88) = 3.48, p = .009, whereas higher parent-reported post-FBT social
      support predicted greater relative weight loss in BSM than control, F(2,141.65) =
      3.28, p = .04. Lower parent-reported post-FBT behavioral problems predicted
      greater relative weight loss in SFM and BSM versus control, F(2,147.84) = 7.37, p
      < .001; higher problems predicted equivalent outcome across treatments.
      CONCLUSION: SFM may improve weight outcomes for FBT completers with initially
      higher eating pathology, whereas extending FBT skills may be effective for those
      with higher familial support. These results suggest that certain pretreatment
      variables moderate the effectiveness of different pediatric weight control
      interventions. Further understanding these findings may help optimally match
      families to treatments.

PMID- 24932570
TI  - The impact of perceived frailty on surgeons' estimates of surgical risk.
AB  - BACKGROUND: Physicians are only moderately accurate in estimating surgical risk
      based on clinical vignettes. We assessed the impact of perceived frailty by
      measuring the influence of a short video of a standardized patient on surgical
      risk estimates. METHODS: Thoracic surgeons and cardiothoracic trainees estimated
      the risk of major complications for lobectomy based on clinical vignettes of
      varied risk categories (low, average, high). After each vignette, subjects viewed
      a randomly selected video of a standardized patient exhibiting either vigorous or
      frail behavior, then reestimated risk. Subjects were asked to rate 5 vignettes
      paired with 5 different standardized patients. RESULTS: Seventy-one physicians
      participated. Initial risk estimates varied according to the vignette risk
      category: low 15.2%+/-11.2% risk; average 23.7%+/-16.1%; high 37.3%+/-18.9%
      (p<0.001 by analysis of variance). Concordant information in vignettes and videos
      moderately altered estimates (high risk vignette, frail video 10.6%+/-27.5%
      increase in estimate, p=0.006; low risk vignette, vigorous video 14.5%+/-45.0%
      decrease, p=0.009). Discordant findings influenced risk estimates more
      substantially (high risk vignette, vigorous video 21.2%+/-23.5% decrease in
      second risk estimate, p<0.001; low risk vignette, frail video 151.9%+/-209.8%
      increase, p<0.001). CONCLUSIONS: Surgeons differentiated relative risk of
      lobectomy based on clinical vignettes. The effect of viewing videos was small
      when vignettes and videos were concordant; the effect was more substantial when
      vignettes and videos were discordant. The information will be helpful in training
      future surgeons in frailty recognition and risk estimation.

PMID- 24932569
TI  - WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS
      pathologies.
AB  - WWOX was cloned as a putative tumor suppressor gene mapping to chromosomal
      fragile site FRA16D. Deletions affecting WWOX accompanied by loss of expression
      are frequent in various epithelial cancers. Translocations and deletions
      affecting WWOX are also common in multiple myeloma and are associated with worse
      prognosis. Metanalysis of gene expression datasets demonstrates that low WWOX
      expression is significantly associated with shorter relapse-free survival in
      ovarian and breast cancer patients. Although somatic mutations affecting WWOX are
      not frequent, analysis of TCGA tumor datasets led to identifying 44 novel
      mutations in various tumor types. The highest frequencies of mutations were found
      in head and neck cancers and uterine and gastric adenocarcinomas. Mouse models of
      gene ablation led us to conclude that Wwox does not behave as a highly penetrant,
      classical tumor suppressor gene since its deletion is not tumorigenic in most
      models and its role is more likely to be of relevance in tumor progression rather
      than in initiation. Analysis of signaling pathways associated with WWOX
      expression confirmed previous in vivo and in vitro observations linking WWOX
      function with the TGFbeta/SMAD and WNT signaling pathways and with specific
      metabolic processes. Supporting these conclusions recently we demonstrated that
      indeed WWOX behaves as a modulator of TGFbeta/SMAD signaling by binding and
      sequestering SMAD3 in the cytoplasmic compartment. As a consequence progressive
      loss of WWOX expression in advanced breast cancer would contribute to the pro
      metastatic effects resulting from TGFbeta/SMAD3 hyperactive signaling in breast
      cancer. Recently, GWAS and resequencing studies have linked the WWOX locus with
      familial dyslipidemias and metabolic syndrome related traits. Indeed, gene
      expression studies in liver conditional KO mice confirmed an association between
      WWOX expression and lipid metabolism. Finally, very recently the first human
      pedigrees with probands carrying homozygous germline loss of function WWOX
      mutations have been identified. These patients are characterized by severe CNS
      related pathology that includes epilepsy, ataxia and mental retardation. In
      summary, WWOX is a highly conserved and tightly regulated gene throughout
      evolution and when defective or deregulated the consequences are important and
      deleterious as demonstrated by its association not only with poor prognosis in
      cancer but also with other important human pathologies such as metabolic syndrome
      and CNS related pathologic conditions. 

PMID- 24932573
TI  - Immobilization of Trichoderma harzianum alpha-amylase on treated wool:
      optimization and characterization.
AB  - alpha-Amylase from Trichoderma harzianum was covalently immobilized on activated
      wool by cyanuric chloride. Immobilized alpha-amylase exhibited 75% of its initial
      activity after 10 runs. The soluble and immobilized alpha-amylases exhibited
      maximum activity at pH values 6.0 and 6.5, respectively. The immobilized enzyme
      was more thermally stable than the soluble one. Various substrates were
      hydrolyzed by immobilized alpha-amylase with high efficiencies compared to those
      of soluble alpha-amylase. The inhibition of the immobilized alpha-amylase by
      metal ions was low as compared with soluble enzyme. On the basis of the results
      obtained, immobilized alpha-amylase could be employed in the saccharification of
      starch processing. 

PMID- 24932572
TI  - Tetrabutylammonium bromide (TBABr)-based deep eutectic solvents (DESs) and their
      physical properties.
AB  - Density, viscosity and ionic conductivity data sets of deep eutectic solvents
      (DESs) formed by tetrabutylammonium bromide (TBABr) paired with ethlyene glycol,
      1,3-propanediol, 1,5-pentanediol and glycerol hydrogen bond donors (HBDs) are
      reported. The properties of DES were measured at temperatures between 303 K and
      333 K for HBD percentages of 66.7% to 90%. The effects of HBDs under different
      temperature and percentages are systematically analyzed. As expected, the
      measured density and viscosity of the studied DESs decreased with an increase in
      temperature, while ionic conductivity increases with temperature. In general,
      DESs made of TBABr and glycerol showed the highest density and viscosity and the
      lowest ionic conductivity when compared to other DESs. The presence of an extra
      hydroxyl group on glycerol in a DES affected the properties of the DES. 

PMID- 24932571
TI  - Overexpression of piRNA pathway genes in epithelial ovarian cancer.
AB  - The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell
      maintenance, genome integrity, DNA methylation and retrotransposon control raises
      possible roles of this pathway in cancer. Indeed aberrant expression of human
      PIWI orthologs and Maelstrom has been observed in various cancers. In this study
      we explored the expression and function of piRNA pathway genes in human ovarian
      cancer, based on our recent work, which showed widespread expression of piRNA
      pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is
      significantly increased in malignant EOC (n = 25) compared to benign tumor
      tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is
      lower in malignant and benign tissues when compared to normal ovary. Sequencing
      of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to
      the introduction of a premature stop codon in the PIWI domain, likely due to a
      splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1,
      2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of
      EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent
      to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and
      expressed in the epithelial cells, we investigated if these two genes affect
      invasiveness of ovarian cancer cell lines that do not normally express these
      genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell
      line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly
      both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells.
      Our findings support a growing body of evidence that shows that genes in this
      pathway are upregulated in cancer. In ovarian cancer we show for the first time
      that Piwil1 transcript may often be abnormal result in non functional product. In
      contrast to what has been observed in other cell types, we found that PIWIL1 and
      MAEL have a repressive effect on cell invasiveness.

PMID- 24932574
TI  - Spontaneous grafting of nitrophenyl groups on carbon: effect of radical scavenger
      on organic layer formation.
AB  - The effect of a radical scavenger (DPPH: 2,2-diphenyl-1-picrylhydrazyl) on the
      spontaneous covalent grafting of nitrophenyl functionalities on a vitreous carbon
      substrate using the 4-nitrobenzene diazonium cation has been studied by
      electrochemical measurements and X-ray photoelectron spectroscopy. The addition
      of micromolar concentrations of DPPH to the diazonium solution efficiently limits
      the multilayer formation and leads to monolayer surface coverage. Control of
      polyaryl layer formation via the capture of the reactive nitrophenyl radical was
      also found to increase the proportion of nitrophenyl groups grafted to the
      surface via azo bridges. This work validates the recently reported strategy using
      a radical scavenger to prevent the formation of a polyaryl layer without
      interfering with direct surface grafting. 

PMID- 24932575
TI  - Importance of the donor:fullerene intermolecular arrangement for high-efficiency
      organic photovoltaics.
AB  - The performance of organic photovoltaic (OPV) material systems are hypothesized
      to depend strongly on the intermolecular arrangements at the donor:fullerene
      interfaces. A review of some of the most efficient polymers utilized in
      polymer:fullerene PV devices, combined with an analysis of reported polymer donor
      materials wherein the same conjugated backbone was used with varying alkyl
      substituents, supports this hypothesis. Specifically, the literature shows that
      higher-performing donor-acceptor type polymers generally have acceptor moieties
      that are sterically accessible for interactions with the fullerene derivative,
      whereas the corresponding donor moieties tend to have branched alkyl substituents
      that sterically hinder interactions with the fullerene. To further explore the
      idea that the most beneficial polymer:fullerene arrangement involves the
      fullerene docking with the acceptor moiety, a family of benzo[1,2-b:4,5
      b']dithiophene-thieno[3,4-c]pyrrole-4,6-dione polymers (PBDTTPD derivatives) was
      synthesized and tested in a variety of PV device types with vastly different
      aggregation states of the polymer. In agreement with our hypothesis, the PBDTTPD
      derivative with a more sterically accessible acceptor moiety and a more
      sterically hindered donor moiety shows the highest performance in bulk
      heterojunction, bilayer, and low-polymer concentration PV devices where fullerene
      derivatives serve as the electron-accepting materials. Furthermore, external
      quantum efficiency measurements of the charge-transfer state and solid-state two
      dimensional (2D) (13)C{(1)H} heteronuclear correlation (HETCOR) NMR analyses
      support that a specific polymer:fullerene arrangement is present for the highest
      performing PBDTTPD derivative, in which the fullerene is in closer proximity to
      the acceptor moiety of the polymer. This work demonstrates that the
      polymer:fullerene arrangement and resulting intermolecular interactions may be
      key factors in determining the performance of OPV material systems. 

PMID- 24932577
TI  - Study by Use of 1H NMR Spectroscopy of the Adsorption and Decomposition of
      Glycine, Leucine, and Derivatives in TiO2 Photocatalysis.
AB  - The photocatalytic decomposition and adsorption of glycine (Gly), Gly-Gly, and
      Gly-Gly-Gly, and leucine (Leu), Leu-Gly, Gly-Leu, and Leu-Gly-Gly, in TiO2 (100%
      anatase crystal form) aqueous suspension were investigated by 1H NMR
      spectroscopy. The side chain of Leu, the carboxylic group, and the peptide bond
      were recognized as the adsorptive sites of the peptides on the surface of TiO2.
      For Gly-Leu and Leu-Gly-Gly, the photocatalytic decomposition that took place
      under UV irradiation resulted from the preferable adsorption of the hydrophobic
      side chain of Leu on the TiO2 surface, while for Gly-Gly and Gly-Gly-Gly, the
      photodecomposition proceeded by weak adsorption of the peptide bonds on the
      surface of TiO2.

PMID- 24932576
TI  - Carbon-dot-based ratiometric fluorescent probe for imaging and biosensing of
      superoxide anion in live cells.
AB  - In this article, a ratiometric fluorescent biosensor for O2(*-) was developed, by
      employing carbon dots (C-Dots) as the reference fluorophore and hydroethidine
      (HE), a specific organic molecule toward O2(*-), playing the role as both
      specific recognition element and response signal. The hybrid fluorescent probe CD
      HE only emitted at 525 nm is ascribed to C-Dots, while HE was almost
      nonfluorescent, upon excitation at 488 nm. However, after reaction with O2(*-), a
      new emission peak ascribed to the reaction products of HE and O2(*-) was clearly
      observed at 610 nm. Meanwhile, this peak gradually increased with the increasing
      concentration of O2(*-) but the emission peak at 525 nm stayed constant, leading
      to a ratiometric detection of O2(*-). The inorganic-organic fluorescent sensor
      exhibited high sensitivity, a broad dynamic linear range of ~5 * 10(-7)-1.4 * 10(
      4) M, and low detection limit down to 100 nM. The present probe also showed high
      accuracy and excellent selectivity for O2(*-) over other reactive oxygen species
      (ROS), metal ions, and so on. Moreover, the C-Dot-based inorganic-organic probe
      demonstrated long-term stability against pH changes and continuous light
      illumination, good cell-permeability, and low cytotoxicity. Accordingly, the
      developed fluorescent biosensor was eventually applied for intracellular
      bioimaging and biosensing of O2(*-) changes upon oxidative stress.

PMID- 24932578
TI  - Immunological disbalance in carcinogenesis.
AB  - It is postulated a conception of immunological disbalance between carcinogenesis
      inhibiting and stimulating antibodies (Ab). Inhibiting Ab prevent the carcinogens
      and estradiol but increase the progesterone penetration into the target cells.
      And vise versa do stimulating Ab. Inhibiting Ab could be blocked by corresponding
      antiidiotypic Ab. The processes of carcinogenesis initiation and promotion are
      intensified when stimulating Ab prevail over inhibiting ones. 

PMID- 24932579
TI  - A role for cAMP-driven transactivation of EGFR in cancer aggressiveness -
      therapeutic implications.
AB  - In many common cancers, production of cAMP boosts cancer proliferation, survival,
      and aggressiveness, reflecting the fact that, through mechanisms that require
      further clarification, cAMP can promote tyrosine phosphorylation, notably
      transactivation of the epidermal growth factor receptor (EGFR). Hormones which
      activate adenylate cyclase in many cancers include PGE2 - often produced by cox-2
      activity within tumors - and adrenergic hormones, acting on beta2 receptors.
      NSAID cyclooxygenase inhibitors, including low-dose aspirin, clearly reduce risk
      for many adenocarcinomas, but the impact of cox-2 inhibitors in clinical cancer
      therapy remains somewhat equivocal. There is increasing evidence that increased
      sympathetic drive, often reflecting psychic stress or tobacco usage, increases
      risk for, and promotes the aggressiveness of, many cancers. The non-specific beta
      antagonist propranolol shows cancer-retardant activity in pre-clinical rodent
      studies, especially in stressed animals, and a limited amount of epidemiology
      concludes that concurrent propranolol usage is associated with superior prognosis
      in breast cancer, ovarian cancer, and melanoma. Epidemiology correlating
      increased resting heart rate with increased total cancer mortality can be
      interpreted as compelling evidence that increased sympathetic drive encourages
      the onset and progression of common cancers. Conversely, hormones which inhibit
      adenylate cyclase activity in cancers may have potential for cancer control;
      GABA, which can be administered as a well-tolerated nutraceutical, has potential
      in this regard. Combination regimens intended to down-regulate cancer cAMP
      levels, perhaps used in conjunction with EGFR inhibitors, may have considerable
      potential for suppressing the contribution of cAMP/EGFR to cancer aggressiveness.
      This model also predicts that certain other hormones which activate adenylate
      cylase in various tissue may play a yet-unsuspected role in cancer induction and
      spread. 

PMID- 24932580
TI  - Thiol oxidation of mitochondrial F0-c subunits: a way to switch off antimicrobial
      drug targets of the mitochondrial ATP synthase.
AB  - A primary goal in antimicrobial drug design is to find molecules which inhibit
      key proteins in bacteria without affecting mammalian homologues. To this aim,
      structural differences between eukaryotic and prokaryotic enzyme proteins
      involved in life processes are widely exploited. The membrane-bound enzyme
      complex ATP synthase synthesizes the energy currency molecule of the cell. Due to
      its bioenergetic role, it represents "the enzyme of life" of all living beings.
      The enzyme complex has the unique bi-functional property of exploiting either the
      electrochemical transmembrane gradient to make ATP or, conversely, the free
      energy of ATP hydrolysis to build an electrochemical gradient across the
      membrane. The catalytic mechanism of ATP synthesis/hydrolysis, based on the
      coupling between the two rotary sectors FO and F1 is shared by eukaryotes and
      prokaryotes. However slight structural differences distinguish prokaryotic ATP
      synthases, embedded in cell membrane, from eukaryotic ones localized in the
      mitochondrial inner membrane. In spite of its fundamental task in living
      organisms, up to now the ATP synthase has been poorly exploited as target in
      antibacterial therapy, mainly due to harmful effects on patients. Recent advances
      shoulder the use of drugs targeting the ATP synthase to fight mycobacteria and
      treat human tuberculosis. Macrolide antibiotics and other antimicrobial drugs
      specifically bind to the c-ring of the membrane-embedded FO domain, thus blocking
      ion translocation through FO which is essential for both ATP synthesis and ATP
      hydrolysis. Our findings show that, once bound to the ATP synthase, probably
      through different binding sites on a common binding region on FO, the macrolide
      antibiotics oligomycin, venturicidin and bafilomycin behave as enzyme inhibitors.
      Interestingly, the c subunits of mitochondrial ATP synthase contain conserved
      cysteine residues which are absent in bacteria. We pointed out that when these
      crucial cysteine thiols are oxidized, the common drug binding site of the enzyme
      is somehow destabilized, thus weakening the enzyme-drug interactions and making
      the ATP synthase insensitive to drug inhibition. On these bases we hypothesize
      that the selective oxidation of these cysteine thiols can be exploited to
      desensitize the mitochondrial ATP synthase to drugs which target FO and maintain
      their inhibitory potency on bacterial ATP synthases. According to our hypothesis,
      this strategy could represent an intriguing tool to prevent adverse effects of
      antimicrobial drugs in mammals, thus enhancing the number of natural and
      synthetic compounds which can be used in therapy. To this aim studies should be
      addressed to the identification and formulation of compounds and/or treatments
      able to selectively oxidize the crucial cysteine thiols of c-subunits without
      affecting the overall functionality of the mitochondrial ATP synthase and other
      thiol containing proteins. 

PMID- 24932581
TI  - Depressive symptoms and career-related goal appraisals: genetic and environmental
      correlations and interactions.
AB  - In order to further understand why depressive symptoms are associated with
      negative goal appraisals, the present study examined the genetic and
      environmental correlations and interactions between depressive symptoms and
      career-related goal appraisals. A total of 1,240 Finnish twins aged 21-26 years
      completed a questionnaire containing items on the appraisal of their career goals
      along five dimensions: importance, progress, effort, strain, and self-efficacy.
      In the same questionnaire, the 10-item General Behavior Inventory assessed
      depressive symptoms. Structural equation modeling was used to evaluate the
      genetic and environmental correlations and gene-environment interactions between
      the career-goal appraisals and depressive symptoms. Associations were identified,
      and were attributed to environmental factors. Of the career-related goal
      appraisals, the shared environmental component was of a higher magnitude for the
      dimension of strain among the depressed compared with non-depressed subjects. The
      results indicate that the interplay between depressive symptoms and negative
      career-related goal appraisals is significantly affected by environmental
      factors, and thus possibly susceptible to targeted interventions. 

PMID- 24932582
TI  - The common variant rs4444235 near BMP4 confers genetic susceptibility of
      colorectal cancer: an updated meta-analysis based on a comprehensive statistical
      strategy.
AB  - OBJECTIVE: We performed an updated meta-analysis, using a comprehensive strategy
      of a logistic regression and a model-free approach, to evaluate more precisely
      the role of the rs4444235 variant near the Bone morphogenetic protein-4 (BMP4)
      gene in susceptibility to colorectal cancer (CRC). METHODS: A total of 19 studies
      with 28770 cases and 28234 controls were included. Metagen system with logistic
      regression was applied to choose the most plausible genetic model for rs4444235.
      Generalized odds ratio (ORG) metric was used to provide a global test of
      relationship between rs4444235 and CRC risk. RESULTS: Metagen analysis suggested
      the rs4444235 fitted best to an additive model. In assessment of the additive
      model, heterogeneity was observed (P = 0.059, I2 = 36.1), and pooled per-allele
      OR was 1.08 (95% CI = 1.05-1.11). Based on the model-free approach, pooled ORG
      was 1.09 (95% CI = 1.05-1.14) under a random-effect model. Stratified analyses
      suggested heterogeneity could be in part explained by population ethnicity, study
      design, sources of controls, and sample size. Sensitivity analysis further
      supported the robust stability of the current results, by showing similar pooled
      estimates before and after sequential removal of each study. CONCLUSIONS: This
      meta-analysis provides a robust estimate of the positive association between the
      rs4444235 and CRC risk and further emphasizes the importance of the rs4444235 in
      CRC risk prediction.

PMID- 24932583
TI  - Dysplastic hepatocytes develop nuclear inclusions in a mouse model of viral
      hepatitis.
AB  - Viral hepatitis resulting in chronic liver disease is an important clinical
      challenge and insight into the cellular processes that drive pathogenesis will be
      critical in order to develop new diagnostic and therapeutic options. Nuclear
      inclusions in viral and non-viral hepatitis are well documented and have
      diagnostic significance in some disease contexts. However, the origins and
      functional consequences of these nuclear inclusions remain elusive. To date the
      clinical observation of nuclear inclusions in viral and non-viral hepatitis has
      not been explored at depth in murine models of liver disease. Herein, we report
      that in a transgenic model of hepatitis B surface antigen mediated hepatitis,
      murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions
      were more likely to express markers of cell proliferation. We also established a
      correlation between these inclusions and oxidative stress. N-acetyl cysteine
      treatment effectively reduced oxidative stress levels, relieved endoplasmic
      reticulum (ER) stress, and the number of nuclear inclusions we observed in the
      transgenic mice. Our results suggest that the presence of nuclear inclusions in
      hepatocytes correlates with oxidative stress and cellular proliferation in a
      model of antigen mediated hepatitis. 

PMID- 24932584
TI  - Traffic-related air pollution and the onset of myocardial infarction: disclosing
      benzene as a trigger? A small-area case-crossover study.
AB  - BACKGROUND AND OBJECTIVES: Exposure to traffic is an established risk factor for
      the triggering of myocardial infarction (MI). Particulate matter, mainly emitted
      by diesel vehicles, appears to be the most important stressor. However, the
      possible influence of benzene from gasoline-fueled cars has not been explored so
      far. METHODS AND RESULTS: We conducted a case-crossover study from 2,134 MI cases
      recorded by the local Coronary Heart Disease Registry (2000-2007) in the
      Strasbourg Metropolitan Area (France). Available individual data were age,
      gender, previous history of ischemic heart disease and address of residence at
      the time of the event. Nitrogen dioxide, particles of median aerodynamic diameter
      <10 um (PM10), ozone, carbon monoxide and benzene air concentrations were modeled
      on an hourly basis at the census block level over the study period using the
      deterministic ADMS-Urban air dispersion model. Model input data were emissions
      inventories, background pollution measurements, and meteorological data. We have
      found a positive, statistically significant association between concentrations of
      benzene and the onset of MI: per cent increase in risk for a 1 ug/m3 increase in
      benzene concentration in the previous 0, 0-1 and 1 day was 10.4 (95% confidence
      interval 3-18.2), 10.7 (2.7-19.2) and 7.2 (0.3-14.5), respectively. The
      associations between the other pollutants and outcome were much lower and in
      accordance with the literature. CONCLUSION: We have observed that benzene in
      ambient air is strongly associated with the triggering of MI. This novel finding
      needs confirmation. If so, this would mean that not only diesel vehicles, the
      main particulate matter emitters, but also gasoline-fueled cars--main benzene
      emitters-, should be taken into account for public health action.

PMID- 24932587
TI  - Gas-forming liver abscess in a patient with multi-organ failure: role of imaging
      and management.
AB  - We present an unusual case of air-containing liver abscess demonstrated on plain
      film and ultrasonography with successful treatment utilizing ultrasound-guided
      drainage in a patient in septic shock. Although surgical drainage is often
      indicated, ultrasound-guided catheter drainage along with supportive antibiotic
      therapy can be a safe treatment alternative in critical patients. 

PMID- 24932585
TI  - Tight coupling of Na+/K+-ATPase with glycolysis demonstrated in permeabilized rat
      cardiomyocytes.
AB  - The effective integrated organization of processes in cardiac cells is achieved,
      in part, by the functional compartmentation of energy transfer processes.
      Earlier, using permeabilized cardiomyocytes, we demonstrated the existence of
      tight coupling between some of cardiomyocyte ATPases and glycolysis in rat. In
      this work, we studied contribution of two membrane ATPases and whether they are
      coupled to glycolysis--sarcoplasmic reticulum Ca2+ ATPase (SERCA) and plasmalemma
      Na+/K+-ATPase (NKA). While SERCA activity was minor in this preparation in the
      absence of calcium, major role of NKA was revealed accounting to ~30% of the
      total ATPase activity which demonstrates that permeabilized cell preparation can
      be used to study this pump. To elucidate the contribution of NKA in the pool of
      ATPases, a series of kinetic measurements was performed in cells where NKA had
      been inhibited by 2 mM ouabain. In these cells, we recorded: ADP- and ATP
      kinetics of respiration, competition for ADP between mitochondria and pyruvate
      kinase (PK), ADP-kinetics of endogenous PK, and ATP-kinetics of total ATPases.
      The experimental data was analyzed using a series of mathematical models with
      varying compartmentation levels. The results show that NKA is tightly coupled to
      glycolysis with undetectable flux of ATP between mitochondria and NKA. Such tight
      coupling of NKA to PK is in line with its increased importance in the
      pathological states of the heart when the substrate preference shifts to glucose.

PMID- 24932588
TI  - Is malnutrition a problem for multiple sclerosis patients?
AB  - Nutritional problems associated with multiple sclerosis (MS) have been observed
      in a number of studies and case reports. However, the prevalence of malnutrition
      in MS patients is currently unknown. The primary aim of this study was to assess
      the prevalence of malnutrition in MS patients and to compare the frequency of
      malnutrition in MS to that of other diseases. The second aim of the study was to
      determine whether malnutrition was associated with MS type, disease duration or
      disability status in MS patients. One hundred two MS patients were included in
      the current study. The control group consisted of 50 patients with other chronic
      neurological diseases. Neurological examination scores, Kurtzke Functional System
      Scale scores, serum albumin levels, sedimentation rate and C reactive protein
      (CRP) were recorded for all patients. Chronic malnutrition was defined as serum
      albumin levels below 3.5 g/dl with normal sedimentation rate and CRP levels.
      Twelve MS patients and one control patient were diagnosed with chronic
      malnutrition, but the difference was not statistically significant (p=0.062). In
      the MS group, MS type, disease duration, number of attacks, Expanded Disability
      State Score and Functional System Scale scores were not significantly different
      regardless of patients' serum albumin levels. We found malnutrition was more
      prevalent in MS patients than in other chronic diseases. Malnutrition in MS
      patients was independent of disease course, disease duration, number of attacks,
      disability status and functional system involvement. These results should be
      confirmed with further prospective studies in larger MS populations from several
      facilities.

PMID- 24932589
TI  - Variant rs1906591 on chromosome 4q25 confers increased risk of cardioembolic
      stroke in Chinese patients.
AB  - Ischemic stroke (IS) is a heterogeneous multifactorial disorder caused by both
      genetic and environmental factors. A genome-wide association study on stroke in
      Caucasians identified a variant on chromosome 4q25 that is significantly
      associated with IS, with the strongest risk for cardioembolic stroke (CES). The
      current study aims to investigate the association of the rs1906591 variant on
      4q25 with IS through a case-control study in a Chinese Han population. A total of
      712 IS patients and 774 control subjects were involved in the current research.
      Stroke subtyping was performed according to the Trial of Org 10172 in Acute
      Stroke Treatment criteria. The genotypes were determined using the SNaPshot
      technique. The association of the genotypes with the risk of IS was estimated
      using logistic regression analysis. The rs1906591 single nucleotide polymorphism
      variant was associated with the CES subtype in both recessive and additive models
      (recessive model: odds ratio [OR]=2.58, 95% confidence interval [CI] 1.47-4.53,
      p=0.001, adjusted OR=2.71, 95% CI 1.48-4.96, p=0.001; additive model: OR=2.50,
      95% CI 1.19-5.25, p=0.015, adjusted OR=2.83, 95% CI 1.24-6.50, p=0.013). This
      result indicates that patients with the AA genotype have a higher rate of CES
      than other genotypes. However, the rs1906591 variant was not significantly
      associated with the overall incidence of stroke or other stroke subtypes. The
      rs1906591 variant is significantly associated with CES in the Chinese Han
      population, but not with other stroke subtypes. 

PMID- 24932586
TI  - Relative hypo- and hypercortisolism are both associated with depression and lower
      quality of life in bipolar disorder: a cross-sectional study.
AB  - BACKGROUND: Depression in unipolar and bipolar disorders is associated with
      hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar
      disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for
      the first time how HPA-axis hypo- and hyperactivity relate to depression and
      disease burden in bipolar disorder. We were interested in studying
      hypocortisolism; characterized by increased HPA-axis negative feedback
      sensitivity and lower basal cortisol levels together with the opposite HPA-axis
      regulatory pattern of hypercortisolism. METHODS: This cross-sectional study
      includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A
      dexamethasone-suppression-test (DST) measures the negative feedback sensitivity
      and a weight-adjusted very-low-dose DST was employed, which is sensitive in
      identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles
      of control post-DST values were used as cut-offs identifying patients exhibiting
      relative hypo-, and hypercortisolism. Self-report questionnaires were employed:
      Beck-Depression-Inventory (BDI), Montgomery-Asberg-Depression-Rating-Scale (MADRS
      S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global
      Assessment-of-Functioning. RESULTS: Patients exhibiting relative hypocortisolism
      expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients
      exhibiting relative hypercortisolism expectedly exhibited elevated basal levels
      (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p =
      0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of
      depression and low overall life quality compared with patients exhibiting mid
      post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression
      ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001)
      for life quality. Patients exhibiting relative hypercortisolism showed 1.9-2.4
      (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies
      of depression and low overall life quality compared with patients exhibiting
      eucortisolism. Adjusted OR:s for depression ranged from 2.2-2.7 (BDI, p = 0.068,
      MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. LIMITATIONS: The
      cross-sectional design and lack of pre-established reference values of the DST
      employed. CONCLUSIONS: Relative hypocortisolism and relative hypercortisolism
      were associated with depression and lower life quality, providing novel insights
      into the detrimental role of stress in bipolar disorder.

PMID- 24932590
TI  - Evaluating initial spine trauma response: injury time to trauma center in PA,
      USA.
AB  - Historical perceptions regarding the severity of traumatic spinal cord injury has
      led to considerable disparity in triage to tertiary care centers. This article
      retrospectively reviews a large regional trauma database to analyze whether the
      diagnosis of spinal trauma affected patient transfer timing and patterns. The
      Pennsylvania Trauma database was retrospectively reviewed. All acute trauma
      patient entries for level I and II centers were categorized for diagnosis,
      mechanism, and location of injury, analyzing transportation modality and its
      influence on time of arrival. A total of 1162 trauma patients were identified
      (1014 blunt injuries, 135 penetrating injuries and 12 other) with a mean
      transport time of 3.9 hours and a majority of patients arriving within 7 hours
      (>75%). Spine trauma patients had the longest mean arrival time (5.2 hours)
      compared to blunt trauma (4.2 hours), cranial neurologic injuries (4.35 hours),
      and penetrating injuries (2.13 hours, p<0.0001). There was a statistically
      significant correlation between earlier arrivals and both cranial trauma
      (p=0.0085) and penetrating trauma (p<0.0001). The fastest modality was a fire
      rescue (0.93 hours) or police (0.63 hours) vehicle with Philadelphia County (1.1
      hour) having the quickest arrival times. Most trauma patients arrived to a
      specialty center within 7 hours of injury. However subsets analysis revealed that
      spine trauma patients had the greatest transit times. Present research trials for
      spinal cord injuries suggest earlier intervention may lead to improved recovery.
      Therefore, it is important to focus on improvement of the transportation triage
      system for traumatic spinal patients.

PMID- 24932591
TI  - Smoking increases the risk of multiple sclerosis in Queensland, Australia.
AB  - There is growing evidence for the role of smoking in the aetiology of multiple
      sclerosis (MS). We have undertaken a large case-control study of smoking in MS
      and assessed this using a regression model. We have confirmed an association
      between increased risk of MS and smoking in Queensland, Australia, a region of
      intermediate risk for MS. The overall adjusted odds ratio was 1.9 (95% confidence
      interval 1.5-2.5) for ever smokers. There was no statistically significant
      difference in the risks for males and females. A number of potential mechanisms
      to explain this association have been postulated including direct and indirect
      (via vitamin D) effects on the immune system. 

PMID- 24932592
TI  - Methods of committing suicide among 2,347 people in Ohio.
AB  - The present study explored gender differences in suicidal methods, aiming to
      identify ways to improve our identification of individuals at risk for suicide.
      Preferred suicide methods vary by demographics; however, method-specific risk
      factors have not been consistently identified. All suicidal deaths (N=2,347) in a
      large urban county were identified over a 15-year period (1994-2008). The
      majority of men used shooting and hanging. In contrast, women relied on a variety
      of methods, including self-poisoning, shooting, hanging, and carbon monoxide
      poisoning. Significant demographic differences are evident among individuals who
      die by shooting and self-poisoning.

PMID- 24932593
TI  - Reframing the goals of care conversation: "we're in a different place".
AB  - PURPOSE: Existing recommendations for communicating with patients with metastatic
      cancer about redefining goals of care when anticancer treatment is unlikely to
      provide benefit are based on limited evidence. This study was designed to elicit
      patient and family views on commonly used communication practices. STUDY DESIGN
      AND METHODS: Participants were 37 patients with metastatic gastrointestinal
      cancer and 20 bereaved family members who listened to audiorecordings of oncology
      fellows instructed to discuss a transition in goals of care with a standardized
      patient for whom evidence-based palliative chemotherapy was no longer effective.
      During semistructured qualitative interviews, participants commented on the
      audiorecordings to give feedback on what they liked or disliked about the
      oncologist's communication. These comments were transcribed and analyzed.
      RESULTS: Three preferred communication practices were identified from
      participants' comments. The first practice involves a necessary disruption of the
      patient's expectations about "trying another chemo" ("We're in a different
      place"). The second practice is offering actionable responses to the disruption
      ("Here's what we can do now"). The third practice is to find a new place that
      acknowledges death is closer yet still allows for "living forward" ("Use your
      inner wisdom"). CONCLUSION: This study of patient and family feedback indicates
      that patients and families perceive a conversation about goals of care to require
      disruption of an existing routine, followed by a process of searching and then
      reconfiguration, rather than a logical decision process. These findings suggest
      that assessing quality from patient perspectives must take into account a period
      of disruption and chaos.

PMID- 24932594
TI  - Interfacial mobility scale determines the scale of collective motion and
      relaxation rate in polymer films.
AB  - Thin polymer films are ubiquitous in manufacturing and medical applications, and
      there has been intense interest in how film thickness and substrate interactions
      influence film dynamics. It is appreciated that a polymer-air interfacial layer
      with enhanced mobility plays an important role in the observed changes and recent
      studies suggest that the length scale xi of this interfacial layer is related to
      film relaxation. In the context of the Adam-Gibbs and random first-order
      transition models of glass formation, these results provide indirect evidence for
      a relation between xi and the scale of collective molecular motion. Here we
      report direct evidence for a proportionality between xi and the average length L
      of string-like particle displacements in simulations of polymer films supported
      on substrates with variable interaction strength and rigidity. This relation
      explicitly links xi to the theoretical scale of cooperatively rearranging
      regions, offering a promising route to experimentally determine this scale of
      cooperative motion. 

PMID- 24932596
TI  - Search for information-bearing components in neural data.
AB  - Multivariate empirical mode decomposition (MEMD) is an important extension of
      EMD, suitable for processing multichannel data. It can adaptively decompose
      multivariate data into a set of intrinsic mode functions (IMFs) that are matched
      both in number and in frequency scale. This method is thus holds great potential
      for the analysis of multi- channel neural recordings as it is capable of ensuring
      all the intrinsic oscillatory modes are aligned not only across channels, but
      also across trials. Given a plethora of IMFs derived by MEMD, a question of
      significant interest is how to identify which IMFs contain information, and which
      IMFs are noise. Existing methods that exploit the dyadic filter bank structure of
      white noise decomposition are insufficient since the IMFs do not always adhere to
      the presumed dyadic relationship. Here we propose a statistical procedure to
      identify information-bearing IMFs, which is built upon MEMD that allows adding
      noise as separate channels to serve as a reference to facilitate IMF
      identification. In this procedure, Wasserstein distance is used to measure the
      similarity between the reference IMF and that from data. Simulations are
      performed to validate the method. Local field potentials from cortex of monkeys
      while performing visual tasks are used for demonstration. 

PMID- 24932595
TI  - Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing
      lateral-flow based assays and upconverting phosphor labels.
AB  - The potential of various quantitative lateral flow (LF) based assays utilizing up
      converting phosphor (UCP) reporters for the diagnosis of schistosomiasis is
      reviewed including recent developments. Active infections are demonstrated by
      screening for the presence of regurgitated worm antigens (genus specific
      polysaccharides), whereas anti-Schistosoma antibodies may indicate ongoing as
      well as past infections. The circulating anodic antigen (CAA) in serum or urine
      (and potentially also saliva) is identified as the marker that may allow
      detection of single-worm infections. Quantitation of antigen levels is a reliable
      method to study effects of drug administration, worm burden and anti-fecundity
      mechanisms. Moreover, the ratio of CAA and circulating cathodic antigen (CCA) is
      postulated to facilitate identification of either Schistosoma mansoni or
      Schistosoma haematobium infections. The UCP-LF assays allow simultaneous
      detection of multiple targets on a single strip, a valuable feature for antibody
      detection assays. Although antibody detection in endemic regions is not a useful
      tool to diagnose active infections, it gains potential when the ratio of
      different classes of antibody specific for the parasite/disease can be
      determined. The UCP-LF antibody assay format allows this type of multiplexing,
      including testing a linear array of up to 20 different targets. Multiple test
      spots would allow detection of specific antibodies, e.g. against different
      Schistosoma species or other pathogens as soil-transmitted helminths. Concluding,
      the different UCP-LF based assays for diagnosis of schistosomiasis provide a
      collection of tests with relatively low complexity and high sensitivity, covering
      the full range of diagnostics needed in control programmes for mapping, screening
      and monitoring.

PMID- 24932598
TI  - Need for comprehensive hormonal workup in the management of adrenocortical tumors
      in children.
AB  - OBJECTIVE: Clinical findings do not reflect the excess hormonal status in
      adrenocortical tumors (ACTs) in children. Identification of abnormal hormone
      secretion may help provide the tumor marker and delineate those patients with a
      risk of adrenal suppression following tumor removal. To analyze the impact of
      complete hormonal assessment regardless of the clinical presentation in hormone
      secreting ACTs in childhood. METHODS: Association of hormonal workup at diagnosis
      with the clinical findings and frequency of adrenal suppression postoperatively
      were analyzed in 18 children with ACT. RESULTS: Seventeen of the 18 patients had
      functional ACT. Clinical findings suggested isolated virilization and isolated
      Cushing's syndrome in 38.8% and 17.6% of patients, respectively. Hormonal workup
      revealed a frequency of 83.3% for hyperandrogenism. The majority of the tumors
      (50%) had mixed type hormonal secretion. Hypercortisolism existed in 28.5% of
      children with isolated virilization and hyperandrogenism was found in 2/3 of
      children with isolated Cushing's syndrome. Various androgens other than
      dehydroepiandrosterone sulfate were also determined to be high in
      hyperandrogenism. Increased testosterone was a highly prevalent tumor marker.
      Nine patients (3 with no signs of hypercortisolism) had adrenal suppression
      following tumor removal which lasted 1-24 months. CONCLUSION: Complete hormonal
      workup showed the predominance of mixed hormone-secreting type of tumor in the
      patients who lacked the appropriate clinical findings and also showed that
      patients lacking signs of Cushing's syndrome could have postoperative adrenal
      suppression. Clinical findings may not reflect the abnormal hormone secretion in
      all cases and tumor markers as well as risk of postoperative adrenal suppression
      can best be determined by complete hormonal evaluation at the time of diagnosis.

PMID- 24932599
TI  - Effects of carbohydrate counting method on metabolic control in children with
      type 1 diabetes mellitus.
AB  - OBJECTIVE: Medical nutritional therapy is important for glycemic control in
      children and adolescents with type 1 diabetes mellitus (T1DM). Carbohydrate
      (carb) counting, which is a more flexible nutritional method, has become popular
      in recent years. This study aimed to investigate the effects of carb counting on
      metabolic control, body measurements and serum lipid levels in children and
      adolescents with T1DM. METHODS: T1DM patients aged 7-18 years and receiving
      flexible insulin therapy were divided into carb counting (n=52) and control
      (n=32) groups and were followed for 2 years in this randomized, controlled study.
      Demographic characteristics, body measurements, insulin requirements, hemoglobin
      A1c (HbA1c) and serum lipid levels at baseline and at follow-up were evaluated.
      RESULTS: There were no statistically significant differences between the groups
      in mean HbA1c values in the year preceding the study or in age, gender, duration
      of diabetes, puberty stage, total daily insulin dose, body mass index (BMI)
      standard deviation score (SDS) and serum lipid values. While there were no
      differences in BMI SDS, daily insulin requirement, total cholesterol, low-density
      lipoprotein and triglyceride values between the two groups (p>0.05) during the
      follow-up, annual mean HbA1c levels of the 2nd year were significantly lower in
      the carb counting group (p=0.010). The mean values of high-density lipoprotein
      were also significantly higher in the first and 2nd years in the carb counting
      group (p=0.02 and p=0.043, respectively). CONCLUSION: Carb counting may provide
      good metabolic control in children and adolescents with T1DM without causing any
      increase in weight or in insulin requirements.

PMID- 24932597
TI  - Prader-Willi syndrome and growth hormone deficiency.
AB  - Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating
      great variability with changing clinical features during patient's life. It is
      characterized by severe hypotonia with poor sucking and feeding difficulties in
      early infancy, followed by excessive eating and gradual development of morbid
      obesity in later infancy or early childhood. The phenotype is most probably due
      to hypothalamic dysfunction which is also responsible for growth hormone (GH) and
      thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and
      hypogonadism. The multidimensional problems of patients with PWS can be managed
      with multidisciplinary approach. Reduced GH secretion, low peak GH response to
      stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS
      patients have been documented in many studies. GH therapy has multiple beneficial
      effects on growth and body composition, motor and mental development in PWS
      patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not
      be started in the presence of obstructive sleep apnea syndrome, adenotonsillar
      hypertrophy, severe obesity and diabetes mellitus. GH treatment should be
      considered for patients with genetically confirmed PWS in conjunction with
      dietary, environmental and life-style measures. 

PMID- 24932600
TI  - Identification of novel ROR2 gene mutations in Indian children with Robinow
      syndrome.
AB  - OBJECTIVE: Robinow syndrome (RS) is an extremely rare genetic disorder
      characterized by short-limbed dwarfism, defects in vertebral segmentation and
      abnormalities in the head, face and external genitalia. Mutations in the ROR2
      gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are
      responsible for the autosomal dominant (AD) form of RS. In AD Robinow patients,
      oral manifestations are more prominent, while hemivertebrae and scoliosis rarely
      occur and facial abnormalities tend to be milder. METHODS: Three unrelated
      patients from different parts of India were studied. These patients were
      diagnosed as RRS due to presence of characteristic fetal facies, mesomelia, short
      stature, micropenis, hemivertebrae and rib abnormalities. One of the patients had
      fetal facies and micropenis but unusually mild skeletal features. This patient's
      mother had mild affection in the form of short stature and prominent eyes.
      Testosterone response to human chorionic gonadotropin was investigated in two
      patients and were normal. The exons and exon-intron boundaries of the ROR2 gene
      were sequenced for all probands. Bioinformatics analysis was done for putative
      variants using SIFT, PolyPhen2 and Mutation Taster. RESULTS: Patients 1, 2 and 3
      were homozygous for c.G545A or p.C182Y in exon 5, c.227G>A or p.G76D in exon 3
      and c.668G>A or p.C223Y in exon 6 respectively. Prenatal diagnosis could be
      performed in an ongoing pregnancy in one family and the fetus was confirmed to be
      unaffected. CONCLUSION: ROR2 mutations were documented for the first time in the
      Indian population. Knowledge of the molecular basis of the disorder served to
      provide accurate counseling and prenatal diagnosis to the families.

PMID- 24932601
TI  - The impact of psycho-educational training on the psychosocial adjustment of
      caregivers of osteogenesis imperfecta patients.
AB  - OBJECTIVE: To investigate the impact of a psycho-educational program developed
      for the caregivers of patients diagnosed with osteogenesis imperfecta (OI).
      METHODS: The participants consisted of 16 caregivers. The study was designed as a
      quasi-experimental pre-test/post-test type study consisting of 10 semi-structured
      three-hour training sessions. The data were collected using the "Introductory
      Information Form" and appropriate scales (Burden Interview, Coping Strategies
      Scale, Problem-Solving Inventory and Psychosocial Adjustment to Illness Scale).
      The results were evaluated by descriptive statistics, correlation analysis, one
      way variance analysis and Bonferroni analysis. RESULTS: Psychosocial adjustment
      levels of the caregivers of OI patients before their participation in the
      educational program were found to be associated with styles of coping with
      stress, problem-solving skills and care burden. After the psycho-educational
      training, the majority of the participants reported favorable changes in their
      lives. Following the offered psycho-education resulted in positive changes in the
      mean scores of the caregivers (p<0.05). CONCLUSION: Before the education program,
      the participants were not able to deal efficiently with many aspects of their
      caregiver responsibilities and suffered from an emotional burden due to lack of
      knowledge. The program appears to have provided them both with support to achieve
      significant psychosocial transformation and with an opportunity to reconsider
      their lives in multiple dimensions.

PMID- 24932602
TI  - Generation of monocyte-derived insulin-producing cells from non-human primates
      according to an optimized protocol for the generation of PCMO-derived insulin
      producing cells.
AB  - OBJECTIVE: The vision of potential autologous cell therapy for the cure of
      diabetes encourages ongoing research. According to a previously published
      protocol for the generation of insulin-producing cells from human monocytes, we
      analyzed whether the addition of growth factors could increase insulin
      production. This protocol was then transferred to a non-human primate model by
      using either blood- or spleen-derived monocytes. METHODS: Human monocytes were
      treated to dedifferentiate into programmable cells of monocytic origin (PCMO). In
      addition to the published protocol, PCMOs were then treated with either activin
      A, betacellulin, exendin 3 or 4. Cells were characterized by protein expression
      of insulin, Pdx-1, C-peptide and Glut-2. After identifying the optimal protocol,
      monocytes from baboon blood were isolated and the procedure was repeated. Spleen
      monocytes following splenectomy of a live baboon were differentiated and analyzed
      in the same manner and calculated in number and volume. RESULTS: Insulin content
      of human cells was highest when cells were treated with activin A and their
      insulin content was 13,000 uU/1 million cells. Insulin-producing cells form
      primate monocytes could successfully be generated despite using human growth
      factors and serum. Expression of insulin, Pdx-1, C-peptide and Glut-2 was
      comparable to that of human neo-islets. Total insulin content of activin A
      treated baboon monocytes was 16,000 uU/1 million cells. CONCLUSION: We were able
      to show that insulin-producing cells can be generated from baboon monocytes with
      human growth factors. The amount generated from one spleen could be enough to
      cure a baboon from experimentally induced diabetes in an autologous cell
      transplant setting.

PMID- 24932603
TI  - Lack of association between peripheral activity of thyroid hormones and elevated
      TSH levels in childhood obesity.
AB  - OBJECTIVE: An elevated thyroid stimulating hormone (TSH) level is a frequent
      finding in obese children, but its association with peripheral hormone metabolism
      is not fully understood. We hypothesized that in obesity, the changes in thyroid
      hormone metabolism in peripheral tissues might lead to dysregulation in the
      thyroid axis. The purpose of this study was to investigate the association of TSH
      with thyroid hormones in a group of obese children as compared to normal-weight
      controls. METHODS: Serum TSH, free thyroxine (fT4) and free triiodothyronine
      (fT3) levels were measured in 101 obese children and in 40 controls. Serum
      reverse T3 (rT3) levels were also measured in a subgroup of 51 obese children and
      in 15 controls. RESULTS: Serum TSH level was significantly higher in obese
      children compared to controls (2.78 vs. 1.99 mIU/L, p<0.001), while no difference
      was found in fT4, fT3, rT3 levels and in fT3/rT3 ratio. In the obese group, fT3
      level positively correlated with fT4 (r=0.217, p=0.033) and inversely with rT3
      (r=-0.288, p=0.045). However, thyroid hormone levels and TSH levels were not
      correlated. CONCLUSION: In obese children, normal fT4, fT3 and rT3 levels suggest
      an undisturbed peripheral hormone metabolism. These levels show no correlation
      with elevated TSH levels.

PMID- 24932604
TI  - Epidemiology of congenital hypothyroidism in Markazi Province, Iran.
AB  - OBJECTIVE: The aim of this study was to investigate the epidemiology of
      congenital hypothyroidism (CH) among newborns in Markazi Province, Iran. METHODS:
      This cross-sectional study was conducted from 2006 to 2012. Blood samples were
      taken between 3 to 5 days after birth from the heel. Thyroid stimulating hormone
      (TSH) was tested using the enzyme-linked immunosorbent assay method and was
      employed as the screening test. Newborns with abnormal screening results (TSH >5
      mIU/L) were re-examined. The data were analyzed using SPSS. RESULTS: A total of
      127 112 infants were screened. Of these, 51.2% were male and 48.8% were female.
      The coverage rate of the screening program was 100%. Of 6102 recalled subjects
      (re-call rate 4.8%), 414 cases with CH were detected, yielding a CH prevalence of
      1:307 (female:male ratio 1:0.95). The prevalence of permanent and transient CH
      was 1:581 and 1:628, respectively. CONCLUSION: This study reveals that the
      prevalence of CH is higher compared to worldwide levels. Comprehensive and
      complementary studies for recognizing related risk factors should be a priority
      for health system research in this province.

PMID- 24932605
TI  - Metabolic bone disease of prematurity: report of four cases.
AB  - Osteopenia of prematurity has become a common problem recently because of
      improved survival rates of infants with very low birth weight (VLBW). The
      incidence of neonatal osteopenia is inversely correlated with gestational age and
      birth weight. Herein, we present four cases of preterm osteopenia that were
      referred to the pediatric endocrinology outpatient clinic with diverse clinical
      and laboratory findings and we discuss the clinical course of these infants with
      regard to bone disease after discharge from the neonatal intensive care unit
      (NICU). This report highlights the importance of enteral calcium, phosphorus and
      vitamin D support at adequate doses following discharge from NICU for preterm
      infants with VLBW who are at risk of metabolic bone disease. 

PMID- 24932606
TI  - Acceleration of puberty during growth hormone therapy in a child with septo-optic
      dysplasia.
AB  - Septo-optic dysplasia (SOD) is a heterogeneous disorder of the central nervous
      system characterized by various endocrinological and neurological findings. It is
      a complex disease caused by a combination of genetic and environmental factors.
      Herein, we report the case of a 5.5-year-old girl who presented with short
      stature and strabismus. Ophthalmological examination revealed bilateral optic
      nerve hypoplasia. Ectopic posterior pituitary and bilateral optic hypoplasia were
      detected on brain magnetic resonance imaging. The presence of bilateral optic
      nerve hypoplasia and hypopituitarism led to the diagnosis of SOD. An abated
      growth hormone (GH) response was found in the GH stimulation test and GH
      replacement therapy was initiated. At the end of the first year of clinical
      follow-up, secondary hypothyroidism was detected and L-thyroxine was added to the
      treatment. At the age of 8.25 years, thelarche was noted and 6 months later, the
      patient presented with menarche. At this time, the bone age was 12 years and the
      basal luteinizing hormone level was 7 mIU/mL. These findings indicated
      acceleration in the process of pubertal development. We report this case (i) to
      emphasize the need to investigate hypopituitarism in cases with bilateral optic
      nerve hypoplasia and (ii) to draw attention to the fact that during the follow-up
      of SOD cases receiving GH therapy, inappropriate acceleration of growth velocity
      and rapid improvement in bone age may be predictive of central precocious puberty
      development. 

PMID- 24932607
TI  - A combination of nifedipine and octreotide treatment in an hyperinsulinemic
      hypoglycemic infant.
AB  - Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent
      hypoglycemia in the neonatal and infancy periods. Mutations in the ABCC8 and
      KCNJ11 genes, which encode subunits of the ATP-sensitive potassium channel in the
      pancreatic beta cell, are identified in approximately 50% of these patients. The
      first-line drug in the treatment of HH is diazoxide. Octreotide and glucagon can
      be used in patients who show no response to diazoxide. Nifedipine, a calcium
      channel blocker, has been shown to be an effective treatment in a small number of
      patients with diazoxide-unresponsive HH. We report a HH patient with a homozygous
      ABCC8 mutation (p.W1339X) who underwent a near-total pancreatectomy at 2 months
      of age due to a lack of response to diazoxide and octreotide treatment. Severe
      hypoglycemic attacks continued following surgery, while the patient was being
      treated with octreotide. These attacks resolved when nifedipine was introduced.
      Whilst our patient responded well to nifedipine, the dosage could not be
      increased to 0.75 mg/kg/day due to development of hypotension, a reported side
      effect of this drug. Currently, our patient, now aged 4 years, is receiving a
      combination of nifedipine and octreotide treatment. He is under good control and
      shows no side effects. In conclusion, nifedipine treatment can be started in
      patients with HH who show a poor response to diazoxide and octreotide treatment. 

PMID- 24932608
TI  - Ring chromosome 13 and ambiguous genitalia.
AB  - Ambiguous genitalia, known to be associated with sex chromosome disorders, may
      also be seen with autosomal chromosome anomalies. Herein, we report a case with
      ambiguous genitalia and ring chromosome 13. Ring chromosome 13 is a rare genetic
      anomaly in which the loss of genetic material determines the clinical spectrum. 

PMID- 24932609
TI  - Heparin-induced hyperkalemia in an extremely-low-birth-weight infant: a case
      report.
AB  - Heparin may cause hyperkalemia by blocking aldosterone biosynthesis in the
      adrenal gland. Dizygotic twin sisters were born by Cesarean section at 25 weeks'
      gestation. The younger sister developed acute hyperkalemia (7.4 mEq/L) at 10 days
      of age. At the time of the development of the hyperkalemia, there were no signs
      of systemic infection, cardiac or renal failure, adrenal insufficiency, or sudden
      anemia. She was receiving no medication other than heparin to maintain the
      vascular catheter. Heparin was changed to dalteparin at 12 days of age. The
      plasma potassium level normalized after 14 days of age. After this change, the
      urinary potassium concentration and the aldosterone and plasma renin activity
      increased. The urinary aldosterone levels before and after the changes were 31
      and 183 pg/MUg creatinine, respectively. When heparin-induced hyperkalemia is
      suspected, stopping the heparin administration facilitates diagnosis and
      treatment; if anticoagulant therapy is required; one treatment option is changing
      from unfractionated heparin to low-molecular-weight heparin. 

PMID- 24932612
TI  - Phonon bandgap engineering of strained monolayer MoS2.
AB  - The phonon band structure of monolayer MoS2 is characteristic of a large energy
      gap between acoustic and optical branches, which protects the vibration of
      acoustic modes from being scattered by optical phonon modes. Therefore, the
      phonon bandgap engineering is of practical significance for the manipulation of
      phonon-related mechanical or thermal properties in monolayer MoS2. We perform
      both phonon analysis and molecular dynamics simulations to investigate the
      tension effect on the phonon bandgap and the compression induced instability of
      the monolayer MoS2. Our key finding is that the phonon bandgap can be narrowed by
      the uniaxial tension, and is completely closed at epsilon = 0.145; while the
      biaxial tension only has a limited effect on the phonon bandgap. We also
      demonstrate the compression induced buckling for the monolayer MoS2. The critical
      strain for buckling is extracted from the band structure analysis of the flexure
      mode in the monolayer MoS2 and is further verified by molecular dynamics
      simulations and the Euler buckling theory. Our study illustrates the uniaxial
      tension as an efficient method for manipulating the phonon bandgap of the
      monolayer MoS2, while the biaxial compression as a powerful tool to intrigue
      buckling in the monolayer MoS2.

PMID- 24932610
TI  - Feedback-related negativity in children with two subtypes of attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: The current model of ADHD suggests abnormal reward and punishment
      sensitivity, although differences in ADHD subgroups are unclear. This study aimed
      to investigate the effect of feedback valence (reward or punishment) and
      punishment magnitude (small or large) on Feedback-Related Negativity (FRN) and
      Late Positive Potential (LPP) in two subtypes of ADHD (ADHD-C and ADHD-I)
      compared to typically developing children (TD) during a children's gambling task.
      METHODS: Children with ADHD-C (n = 16), children with ADHD-I (n = 15) and
      typically developing children (n = 15) performed a children's gambling task under
      three feedback conditions: large losses, small losses and gains. FRN and LPP
      components in brain potentials were recorded and analyzed. RESULTS: In TD
      children and children with ADHD-C, large loss feedback evoked more negative FRN
      amplitudes than small loss feedback, suggesting that brain sensitivity to the
      punishment and its magnitude is not impaired in children with ADHD-C. In contrast
      to these two groups, the FRN effect was absent in children with ADHD-I. The LPP
      amplitudes were larger in children with ADHD-C in comparison with those with ADHD
      I, regardless of feedback valence and magnitude. CONCLUSION: Children with ADHD-C
      exhibit intact brain sensitivity to punishment similar to TD children. In
      contrast, children with ADHD-I are significantly impaired in neural sensitivity
      to the feedback stimuli and in particular, to punishment, compared to TD and ADHD
      C children. Thus, FRN, rather than LPP, is a reliable index of the difference in
      reward and punishment sensitivity across different ADHD-subcategories.

PMID- 24932611
TI  - CoCl2, a mimic of hypoxia, induces formation of polyploid giant cells with stem
      characteristics in colon cancer.
AB  - The induction of polyploidy is considered the reproductive end of cells, but
      there is evidence that polyploid giant cancer cells (PGCCs) contribute to cell
      repopulation during tumor relapse. However, the role of these cells in the
      development, progression and response to therapy in colon cancer remains
      undefined. Therefore, the main objective of this study was to investigate the
      generation of PGCCs in colon cancer cells and identify mechanisms of formation.
      Treatment of HCT-116 and Caco-2 colon cancer cells with the hypoxia mimic CoCl2
      induced the formation of cells with larger cell and nuclear size (PGCCs), while
      the cells with normal morphology were selectively eliminated. Cytometric analysis
      showed that CoCl2 treatment induced G2 cell cycle arrest and the generation of a
      polyploid cell subpopulation with increased cellular DNA content. Polyploidy of
      hypoxia-induced PGCCs was confirmed by FISH analysis. Furthermore, CoCl2
      treatment effectively induced the stabilization of HIF-1alpha, the differential
      expression of a truncated form of p53 (p47) and decreased levels of cyclin D1,
      indicating molecular mechanisms associated with cell cycle arrest at G2.
      Generation of PGCCs also contributed to expansion of a cell subpopulation with
      cancer stem cells (CSCs) characteristics, as indicated by colonosphere formation
      assays, and enhanced chemoresistance to 5-fluorouracil and oxaliplatin. In
      conclusion, the pharmacological induction of hypoxia in colon cancer cells causes
      the formation of PGCCs, the expansion of a cell subpopulation with CSC
      characteristics and chemoresistance. The molecular mechanisms involved, including
      the stabilization of HIF-1 alpha, the involvement of p53/p47 isoform and cell
      cycle arrest at G2, suggest novel targets to prevent tumor relapse and treatment
      failure in colon cancer. 

PMID- 24932613
TI  - Mitochondrial DNA variation and virologic and immunological HIV outcomes in
      African Americans.
AB  - OBJECTIVE: To evaluate the impact of mitochondrial DNA (mtDNA) haplogroups on
      virologic and immunological outcomes of HIV infection. DESIGN: HAART-naive
      African American adolescent participants to the Reaching for Excellence in
      Adolescent Care and Health study. METHODS: The mtDNA haplogroups were inferred
      from sequenced mtDNA hypervariable regions HV1 and HV2 and their predictive value
      on HIV outcomes were evaluated in linear mixed models, controlled for human
      leukocyte antigen (HLA)-B27, HLA-B57 and HLA-B35-Px alleles and other covariates.
      RESULTS: We report data showing that the mtDNA L2 lineage, a group composed of
      L2a, L2b and L2e mtDNA haplogroups in the studied population, is significantly
      associated (beta  = -0.08; Bonferroni-adjusted P = 0.004) with decline of CD4 T
      cells (median loss of 8 +/- 1 cells per month) in HAART-naive HIV-infected
      individuals of African American descent (n = 133). No significant association (P
      < 0.05) with set-point viral load was observed with any of the tested mtDNA
      haplogroups. The present data concur with previous findings in the AIDS Clinical
      Trials Group study 384, implicating the L2 lineage with slower CD4 T-cell
      recovery after antiretroviral therapy in African Americans. CONCLUSIONS: Whereas
      the L2 lineage showed an association with unfavorable immunological outcomes of
      HIV infection, its phylogenetic divergence from J and U5a, two lineages
      associated with accelerated HIV progression in European Americans, raises the
      possibility that interactions with common nucleus-encoded variants drive HIV
      progression. Disentangling the effects of mitochondrial and nuclear gene variants
      on the outcomes of HIV infection is an important step to be taken toward a better
      understanding of HIV/AIDS pathogenesis and pharmacogenomics.

PMID- 24932615
TI  - Energy balance at a crossroads: translating the science into action.
AB  - One of the major challenges facing the United States is the high number of
      overweight and obese adults and the growing number of overweight and unfit
      children and youth. To improve the nation's health, young people must move into
      adulthood without the burden of obesity and its associated chronic diseases.
      PURPOSE: To address these issues, the American College of Sports Medicine, the
      Academy of Nutrition and Dietetics, and the US Department of
      Agriculture/Agriculture Research Service convened an expert panel meeting in
      October 2012 titled "Energy Balance at a Crossroads: Translating the Science into
      Action." Experts in the fields of nutrition and exercise science came together to
      identify the biological, lifestyle, and environmental changes that will most
      successfully help children and families attain and manage energy balance and tip
      the scale toward healthier weights. METHODS: Two goals were addressed: 1)
      professional training and 2) consumer/community education. The training goal
      focused on developing a comprehensive strategy to facilitate the integration of
      nutrition and physical activity (PA) using a dynamic energy balance approach for
      regulating weight into the training of undergraduate and graduate students in
      dietetics/nutrition science, exercise science/PA, and pre-K-12 teacher
      preparation programs and in training existing cooperative extension faculty. The
      education goal focused on developing strategies for integrating dynamic energy
      balance into nutrition and PA educational programs for the public, especially
      programs funded by federal/state agencies. RESULTS: The meeting expert presenters
      and participants addressed three key areas: 1) biological and lifestyle factors
      that affect energy balance, 2) undergraduate/graduate educational and training
      issues, and 3) best practices associated with educating the public about dynamic
      energy balance. CONCLUSIONS: Specific consensus recommendations were developed
      for each goal.

PMID- 24932614
TI  - Antiretroviral therapy modifies the genetic effect of known type 2 diabetes
      associated risk variants in HIV-infected women.
AB  - OBJECTIVE: Type 2 diabetes mellitus incidence is increased in HIV-infected
      persons. We examined the associations of diabetes mellitus with known diabetes
      mellitus-risk alleles from the general population in the context of HIV
      infection, and explored effect modification by combination antiretroviral therapy
      (cART). METHODS: The Women's Interagency HIV Study is a prospective cohort of HIV
      infected women. Seventeen European-derived diabetes mellitus-risk polymorphisms
      were genotyped in the eligible participants of the Women's Interagency HIV Study.
      Analyses were run separately for non-African Americans (Whites, Hispanics,
      Asians, and other; n = 378, 49 with incident diabetes mellitus) and African
      Americans (n = 591, 49 with incident diabetes mellitus). Cox proportional-hazards
      models were fit to estimate hazard ratios for diabetes mellitus overall and
      within strata of cART. RESULTS: In non-African Americans, heterogeneity across
      cART regimen was observed for nine of the 14 polymorphisms (phet < 0.05). One
      polymorphism was statistically significantly inversely associated with diabetes
      mellitus risk among women taking two nucleotide reverse transcriptase inhibitors
      (NRTIs) + non-nucleotide reverse transcriptase inhibitor (NNRTI). Five
      polymorphisms were statistically significantly associated with diabetes mellitus
      among women treated with at least two NRTIs + at least one protease inhibitor and
      one polymorphism was associated with diabetes mellitus among those treated with
      at least three NRTIs +/- NNRTI. The hazard ratio per risk allele for IGF2BP2
      rs1470579 was 2.67 (95% confidence interval 1.67-4.31) for women taking cART with
      at least two NRTIs + at least one protease inhibitor and 2.45 (95% confidence
      interval 1.08-5.53) in women taking at least three NRTIs +/- NNRTI (phet = 2.50 *
      10-3). No such associations were observed in the African Americans. CONCLUSIONS:
      Genetic susceptibility to diabetes mellitus, based on the variants studied, is
      substantially elevated among HIV-infected women using cART containing three or
      more NRTI/protease inhibitor components. A personalized medicine approach to cART
      selection may be indicated for HIV-infected persons carrying these diabetes
      mellitus-risk variants.

PMID- 24932617
TI  - Association between total, processed, red and white meat consumption and all
      cause, CVD and IHD mortality: a meta-analysis of cohort studies.
AB  - An association between processed and red meat consumption and total mortality has
      been reported by epidemiological studies; however, there are many controversial
      reports regarding the association between meat consumption and CVD and IHD
      mortality. The present meta-analysis was carried out to summarise the evidence
      from prospective cohort studies on the association between consumption of meat
      (total, red, white and processed) and all-cause, CVD and IHD mortality. Cohort
      studies were identified by searching the PubMed and ISI Web of Knowledge
      databases. Risk estimates for the highest v. the lowest consumption category and
      dose-response meta-analysis were calculated using a random-effects model.
      Heterogeneity among the studies was also evaluated. A total of thirteen cohort
      studies were identified (1 674 272 individuals). Subjects in the highest category
      of processed meat consumption had 22 and 18 % higher risk of mortality from any
      cause and CVD, respectively. Red meat consumption was found to be associated with
      a 16 % higher risk of CVD mortality, while no association was found for total and
      white meat consumption. In the dose-response meta-analysis, an increase of 50 g/d
      in processed meat intake was found to be positively associated with all-cause and
      CVD mortality, while an increase of 100 g/d in red meat intake was found to be
      positively associated with CVD mortality. No significant associations were
      observed between consumption of any type of meat and IHD mortality. The results
      of the present meta-analysis indicate that processed meat consumption could
      increase the risk of mortality from any cause and CVD, while red meat consumption
      is positively but weakly associated with CVD mortality. These results should be
      interpreted with caution due to the high heterogeneity observed in most of the
      analyses as well as the possibility of residual confounding.

PMID- 24932616
TI  - A predictive model of the dynamics of body weight and food intake in rats
      submitted to caloric restrictions.
AB  - Dynamics of body weight and food intake can be studied by temporally perturbing
      food availability. This perturbation can be obtained by modifying the amount of
      available food over time while keeping the overall food quantity constant. To
      describe food intake dynamics, we developed a mathematical model that describes
      body weight, fat mass, fat-free mass, energy expenditure and food intake dynamics
      in rats. In addition, the model considers regulation of food intake by leptin,
      ghrelin and glucose. We tested our model on rats experiencing temporally variable
      food availability. Our model is able to predict body weight and food intake
      variations by taking into account energy expenditure dynamics based on a memory
      of the previous food intake. This model allowed us to estimate this memory lag to
      approximately 8 days. It also explains how important variations in food
      availability during periods longer than these 8 days can induce body weight
      gains. 

PMID- 24932618
TI  - Objective measures for functional diagnostic of the upper airways: practical
      aspects.
AB  - OBJECTIVE: To review the main papers published on the main available tests to
      obtain objective values of nasal patency and to demonstrate aspects of their use
      in medical practice. METHODOLOGY: We performed a non-systematic review of the
      MEDLINE and LILACS databases, and the most relevant articles were selected.
      RESULTS: Objective evaluations are important in epidemiological studies and in
      monitoring of patients with nasal obstruction. There is a wide variety of
      objective tests of nasal function; among them acoustic rhinometry,
      rhinomanometry, and peak nasal inspiratory flow (PNIF) are currently the most
      used tests. CONCLUSION: The choice of the method to evaluate nasal function
      depends on the conditions of each health service. PNIF has been highlighted as a
      simple and reliable alternative that provides easy-to-interpret results, and is
      thus an attractive method for clinical practice.

PMID- 24932619
TI  - Cocaine induced midline destructive lesions.
AB  - PURPOSE: Review of the literature concerning cocaine induced midline destructive
      lesions (CIMDL). METHODS: We reviewed the English literature regarding CIMDL
      involving the nose and its surrounding structures. The review is based on a
      search of the US National Library of Medicine (PubMed) online database from
      January 1st, 1982 to March 31st, 2013. RESULTS: CIMDL is a pathology that mimics
      systemic diseases with positive anti-neutrophil cytoplasmic antibodies (ANCA).
      The prevalence of CIMDL is considered to be about 4.8% among cocaine users.
      Clinical manifestations include hyposmia, facial pain, crusting, ulcers, nasal
      septal perforation, palatal perforation, sinus wall destruction, orbital erosion
      and damage of the anterior skull base. The presence of ANCA directed against
      human neutrophil elastase (HNE) is the most distinguishing feature of CIMDL.
      Toxicological tests, indirect immunofluorescence microscopy, antigen specific
      solid assay testing, histopathological analysis, apoptosis assay and MRI imaging
      concur in the clinical identification of CIMDL. The pathogenesis of CIMDL is
      poorly understood and implicates inflammatory, infective, proapoptotic and
      autoimmune mechanisms. CONCLUSION: CIMDL must be readily recognized by clinicians
      to provide appropriate treatment. Immunosuppressive therapy has no role in the
      treatment of CIMDL. Only abstinence can interrupt the progression of the disease.

PMID- 24932620
TI  - Use of peak nasal inspiratory flowmetry and nasal decongestant to evaluate
      outcome of septoplasty with radiofrequency coblation of the inferior turbinate.
AB  - BACKGROUND: To investigate the role of peak nasal inspiratory flowmetry (PNIF) in
      evaluating inspiratory improvements in patients who underwent both septoplasty
      and inferior turbinate coblation by radiofrequency (ITC-RF). METHODS: One hundred
      and eight patients underwent both Cottle's septoplasty and ITC-RF. PNIF
      measurements were performed in all patients in the preoperative period and 6
      months postoperatively. All measurements were made both before and after
      decongestion of the nasal cavity with oxymetazoline spray. RESULTS: Mean
      preoperative PNIF measurements differed significantly: 104.3 +/- 33.6 L/min vs
      136.1 +/- 27.7 L/min before and after oxymetazoline decongestion, respectively.
      Mean postoperative PNIF measurements were 139.2 +/- 30.8 L/min and 151.2 +/- 32.3
      L/min before and after decongestion, respectively. Preoperatively the mean
      difference between before and after decongestion was 32.1 +/- 16.3 L/min.
      Postoperatively the mean difference was 11.8 +/- 11.1 L/min. CONCLUSION: PNIF can
      be used in the assessment of ITC-RF outcomes with the aid of nasal decongestants,
      even in patients who also underwent septoplasty.

PMID- 24932621
TI  - Nasal peak inspiratory flow (NPIF) as a diagnostic tool for differentiating
      decongestable from structural nasal obstruction.
AB  - BACKGROUND: Identifying the cause of nasal obstruction is critical before
      surgical intervention. Structural nasal obstruction, due to nasal valve stenosis,
      is unlikely to benefit from simple septoplasty and turbinate reduction. This
      study assesses changes in nasal peak inspiratory flow (NPIF) as a tool for
      discriminating decongestable versus structural obstruction. METHODOLOGY: Cross
      sectional study of patients undergoing nasal airflow assessment was performed.
      Rhinomanometry, nasal obstruction visual analogue scores (VAS) and NPIF were
      performed pre- and post-decongestion. Population groups were defined with
      decongestable or structural obstruction by relative post-decongestion changes in
      airways resistance and symptoms. RESULTS: Fifty two patients were assessed, 24
      with decongestable, 28 with structural obstruction. Pre- and post-decongestion
      NPIF were similar between groups. Absolute and percentage NPIF change were larger
      with decongestable versus structural obstruction. Sensitivity and specificity for
      predicting decongestable obstruction were 75.0% and 60.7% for NPIF increase >20
      L/min; 75.0% and 64.3% for NPIF increase >20%. The respective positive predictive
      values were 62.1% and 64.3%. CONCLUSION: NPIF increase after decongestion is
      larger with decongestable than structural nasal obstruction. NPIF alone cannot
      discriminate the two conditions and does not replace more formal assessment.

PMID- 24932622
TI  - Examination versus subjective nasal obstruction in the evaluation of the nasal
      septal deviation.
AB  - BACKGROUND: Nasal septal deviation (NSD) is a frequent complaint among patients
      in an otolaryngology clinic. The prevalence of NSD varies in different
      populations and NSD classification schemes are complex. METHODS: We aimed to
      determine the prevalence of NSD in a population of Turkish young males using a
      new NSD classification method that we developed. We compared the results with
      patients' complaints. All patients underwent two nasal examinations, which were
      performed using a nasal speculum with and without administration of
      vasoconstrictor agents. Inferior Concha Hypertrophy (ICH) was evaluated in the
      first examination and NSDs were scored during the second examination. All
      findings were recorded according to our classification scheme. Severity of nasal
      obstruction was subjectively evaluated by using a visual analogue scale (VAS).
      RESULTS: We found a significant association between prevalence of NSD and nasal
      injuries, but there was no association between the mode of delivery and
      prevalence of NSD. Surprisingly, about 30 % of the participants with NSD had no
      complaint of nasal obstruction. Although most of the participants in the study
      had no severe nasal obstruction complaint, we found an association between NSD
      presence and patient's VAS. CONCLUSION: NSD is very frequent in the Turkish
      population and most often related to trauma; however, its effect on patient
      quality of life varies.

PMID- 24932623
TI  - External nasal valve collapse: validation of novel outcome measurement tool.
AB  - BACKGROUND: We aim to validate a clinical scoring system of external nasal valve
      collapse. External nasal valve collapse is a rare and challenging condition. We
      attempted to simplify the examination of the external valve, the surgical
      planning and the outcome measure. To validate our external valve score, we first
      assessed its reliability (inter-rater agreement and test-retest repeatability).
      We secondly considered the clinical relevance by using our scoring system in
      patients undergoing septorhinoplasty for external valve collapse. METHODOLOGY:
      For validation, 16 Rhinologists scored patients separately on two occasions. For
      the clinical relevance, 26 patients with external valve collapse were scored pre-
      and post-operatively (responsiveness). The external valve score was correlated to
      peak nasal inspiratory flow. RESULTS: The devised scoring system was reliable
      (substantial agreement between 16 surgeons with reproducibility over time). All
      patients in our prospective series showed significant improvement in their
      external valve score. The quality of life measured by the SNOT-22 tool showed
      significant improvement after surgery. CONCLUSION: External nasal valve collapse
      can be diagnosed and graded using this simple scoring system in the outpatient
      clinic. This paper reinforces the pivotal role of septorhinoplasty surgery in
      nasal airway reconstruction and the ongoing need to quantify success.

PMID- 24932624
TI  - Application of Peak Nasal Inspiratory Flow reference values in the treatment of
      allergic rhinitis.
AB  - OBJECTIVE: To assess the applicability of the Peak Nasal Inspiratory Flow (PNIF)
      curves in follow-up of children in the treatment of allergic rhinitis. METHODS:
      Prospective study of 40 patients with AR, grouped in corticosteroid spray versus
      physiological saline solution use. Follow up for 10 weeks through clinical score
      and PNIF percentages in relation to the reference curves, with was-out at week 8.
      Statistical assessment of the effect of treatment on variation of PNIF and
      clinical score was calculated by ANOVA model and Multiple Comparison of Means
      Test - Least Significant Difference. RESULTS: There was a statistically
      significant influence of the group, time and interaction between time and group
      on PNIF percentages. Throughout follow up, patients from the treatment group had
      mean PNIF percentages significantly higher than the placebo group. Clinical score
      results also demonstrated a statistically significant influence between the
      groups, time and interaction between time and group. CONCLUSION: Increase in PNIF
      percentage values observed in children treated with intranasal corticosteroids
      revealed the applicability of PNIF curves in their follow up.

PMID- 24932625
TI  - A critical appraisal of analyzing nasal provocation test results in allergen
      immunotherapy trials.
AB  - BACKGROUND: The statistical analysis of nasal provocation tests is very complex.
      We compared the conventional analysis with the maximally selected test statistics
      and the hierarchical ordered logistic model. METHODS: We re-analyzed data from a
      trial with 112 patients suffering from grass pollen allergy. The patients had
      been randomized to receive either intralymphatic immunotherapy (ILIT) or
      subcutaneous immunotherapy (SCIT). RESULTS: The conventional analysis indicated
      that the logarithmized ratio between the pre- and the post-treatment threshold
      concentration was significantly lower for ILIT than for SCIT. The maximally
      selected test statistics was used to test different threshold symptom scores that
      would imply positive clinical symptoms at the given allergen concentration. A
      threshold score of 3 maximised the difference in improvement between the ILIT and
      the SCIT groups. The hierarchical ordered logistic model does not take threshold
      allergen concentrations as the basis for analysis, but the single scores measured
      at each concentration. This approach simultaneously considers the treatment
      effect (ILIT versus SCIT), the time effect (pre- versus post-treatment), and the
      dose effect (different allergen concentrations). The hierarchical ordered
      logistic model revealed that the clinical improvement was greater after ILIT than
      after SCIT. CONCLUSION: As the choice of method can affect the outcome,
      guidelines for analysis are highly needed.

PMID- 24932626
TI  - Role of inflammation in non-allergic rhinitis.
AB  - OBJECTIVE: To investigate the role of inflammation in non-allergic rhinitis (NAR)
      patients in a large series to establish the prevalence of different NAR-subtypes,
      clinical features and the role of nasal cytology in the diagnostic algorithm.
      METHODOLOGY: Patients were selected out of 3650 individuals who spontaneously
      presented at our institution. We consecutively enrolled 519 NAR-patients in an
      analytical cross-sectional study between November 2007 and June 2013 (level of
      evidence: 3b). All patients underwent rhinological evaluation including symptoms
      questionnaire, endoscopy, CT scan, allergy tests and nasal cytology. RESULTS: The
      inflammatory cell infiltrate affects the severity of symptoms differently,
      allowing for identification of different phenotypes of NAR. We distinguished two
      groups: "NAR without inflammation"(NAR-) and "NAR with inflammation"(NAR+), in
      addition to different NAR-subtypes with inflammation. A significant difference
      was observed in terms of clinical symptoms and association with comorbidities
      (previously diagnosed asthma and aspirin intolerance) between NAR-, NAR+ and
      between different NAR+ subtypes. CONCLUSION: Our data suggest that NAR- and NAR
      with neutrophils behave similarly, showing lower symptom score values and a lower
      risk of association with comorbidities compared to NAR with eosinophils and mast
      cells (singularly or mixed). In our belief it is very important to establish the
      presence and type of inflammation in non-allergic rhinitis patients and nasal
      cytology is a very useful test in correct differential diagnosis.

PMID- 24932627
TI  - Bacterial biofilms in patients with chronic rhinosinusitis: a confocal scanning
      laser microscopy study.
AB  - BACKGROUND: Recent research into the pathophysiology of chronic rhinosinusitis
      suggests an important role for biofilms. They can be detected in both healthy and
      diseased nasal mucosa. Several different methods of detecting biofilms have been
      described. This study investigates the presence of biofilm in a larger group of
      patients with chronic rhinosinusitis undergoing primary functional endoscopic
      surgery. METHODS: Sixty-one patients with chronic rhinosinusitis and 25 controls,
      with septal deviation, were included from 2010 to 2012. Endonasal biopsies were
      harvested during surgery, snap frozen in isopentane, cooled on dry ice and stored
      at -80oC. The samples were prepared with Invitrogens' BacLight LiveDead kit, and
      investigated with confocal scanning laser microscopy for the presence of biofilm.
      RESULTS: In the chronic rhinosinusitis group 55/61 were biofilm positive as
      opposed to 14/25 in the control group. The difference was highly significant. The
      odds ratio was 7.2. CONCLUSION: Patients with chronic rhinosinusitis have a
      highly significant increased point prevalence of biofilms compared to controls.

PMID- 24932628
TI  - An unexpected route for otolaryngology bacterial contamination with a Venturi
      atomizer.
AB  - BACKGROUND: The Venturi-principle atomizer is a commonly used device in
      otolaryngology practices. The purpose of this study is to evaluate the possible
      route of bacterial contamination from the nasal vestibule to the atomizer tip
      through the jet airflow created during the use of the Venturi atomizer. METHODS:
      Thirty nostrils from 15 enrolled volunteers were tested. The aerosols generated
      by spraying sterilized saline into the nostrils were collected using a specially
      made aerosol-collecting nozzle cap. The collected samples were sent for bacterial
      culture, and nasal vestibular swab cultures were performed for comparison.
      RESULTS: In the aerosol-exposed group, 18 out of 30 samples (60%) were positive
      for bacterial growth, confirming the bacterial contamination from the nasal
      vestibule to the atomizer tip through the reverse jet airflow. The bacteria
      species in 8 of the 18 positive samples were identical to those from the nasal
      swab culture results from the same nostril. CONCLUSION: In ordinary
      otolaryngology practices, there are significant risks for bacterial contamination
      from the nasal vestibule to the tip of the Venturi atomizer even without direct
      contact. Clinicians must be more aware of this pattern of contamination, which
      has not been reported in the existing literature.

PMID- 24932629
TI  - Mechanical disfunction in the mucosal oedema formation of patients with nasal
      polyps.
AB  - BACKGROUND: Nasal polyposis (NP) is characterized by an anomalous tissue growth
      with oedema and a lack of extracellular matrix. In this study, we investigated
      whether a mechanical disfunction of the forces that act in oedema formation is
      present in NP. METHODS: We compared the interstitial hydrostatic pressure
      behaviour during a saline solution infusion between healthy nasal mucosa
      (inferior and middle turbinate from 10 patients) and inflamed nasal mucosa from
      NP patients (inferior, middle turbinate and a nasal polyp from 6 patients). We
      used Controlled Disc Stimulation equipment to compare the curve Pressure/Volume
      created during the saline solution infusion. RESULTS: The pressure at 0.2 ml
      infusion was lower in the middle turbinate of NP patients than in the middle
      turbinate of control patients. The lowest P/V mean assessed was in the polypoid
      tissue. CONCLUSIONS: The interstitial hydrostatic pressure showed different
      behaviour during liquid infusion in nasal mucosa from NP patients when compared
      with healthy nasal mucosa. This study allows us to cogitate on a new
      pathophysiological mechanism contributing to the development of the NP.

PMID- 24932630
TI  - Importance of nasal septal cartilage perichondrium for septum strength mechanics:
      a cadaveric study.
AB  - OBJECTIVE: This study aimed to investigate the biomechanical qualities of the
      perichondrium and cartilage, and to determine the strength of the septal
      cartilage against bending forces. STUDY DESIGN: This paper describes an
      experimental cadaver study. MATERIALS AND METHODS: The nasal septal cartilages of
      14 fresh cadavers (8 hours postmortem) were excised from the cadavers and cut
      into two strips: one with the perichondrium (group A) and one without
      perichondrium (group B). A bending test was then performed on the strips.
      RESULTS: The deflection of group A strips was larger than the deflection of group
      B strips. Flexural strength was also larger in group A strips compared to group B
      strips. The average modulus of elasticity was 122% higher in group A compared to
      group B. All conducted tests revealed statistically significant differences
      between groups. CONCLUSION: This study objectively shows that the perichondrium
      provides the cartilage with a 25% bending strength.

PMID- 24932631
TI  - Cultural adaptation of an olfactory test: the odour in bottle test. [corrected].
AB  - OBJECTIVES: To compare the size of the nasal septal body (SB) and inferior
      turbinate (IT) of subjects grouped by sex and age. METHOD: We measured SB and IT
      areas (in cm2) bilaterally in computed tomography (CT) sections of 150 paranasal
      sinuses from 72 males and 78 females. RESULTS: The right and left SB areas were
      smaller in females than in males. In the <= 25-year-old group, the right IT (RIT)
      was significantly smaller in females than in males. In the 26-35 and 46-45 age
      groups, the right SB (RSB) was significantly smaller in females than in males.
      CONCLUSION: The nasal SB may play a role in nasal physiology similar to a
      turbinate and help support optimal airflow. The vascular and glandular structures
      of the SB should be investigated in detail, and minimal invasive procedures
      should be performed in nasal surgery to avoid damaging essential structures.

PMID- 24932632
TI  - Resonator properties of paranasal sinuses: preliminary results of an anatomical
      study.
AB  - BACKGROUND: The contribution of the nasal and paranasal cavities to vocal tract
      resonator properties is unclear as are voice effects of sinus surgery. Here we
      investigate resonance phenomena of paranasal sinuses with and without selective
      occlusion of the middle meatus and maxillary ostium in a cadaver. METHODOLOGY:
      Nasal and paranasal cavities of a Thiel-embalmed cadaver were excited by sine
      tone sweeps from an earphone in the epipharynx. The response was picked up by a
      microphone at the nostrils. Different conditions with blocked and unblocked
      middle meatus were tested. Additionally, infundibulotomy was performed allowing
      direct access to and selective occlusion of the maxillary ostium. RESULTS:
      Responses showed high reproducibility. Minor effects appeared after removal of
      meatal occlusion. A marked low frequency dip was detected after removal of
      occlusion of maxillary ostium following infundibulotomy. CONCLUSION: Reproducible
      frequency responses of nasal tract can be derived from cadaver measurements.
      Marked acoustic effects of the maxillary sinus appeared only after direct
      exposure of the maxillary ostium following infundibulotomy.

PMID- 24932633
TI  - Multiple causes for rhinolithiasis.
AB  - BACKGROUND: Rhinoliths are rare affections of the main nasal cavity and the
      paranasal sinuses. Initially, as a result of their low incidence, they are often
      incorrectly classified as calcified tumors in clinical examination. METHODOLOGY:
      We have identified three cases in our patient population and evaluated the
      clinical symptoms as well as the pathological findings and the causes of the
      disease. RESULTS: Due to their extension and the respective clinical pattern, all
      masses were surgically removed under endotracheal anesthesia. The
      histopathological findings comprised an ectopic tooth, a vegetable (most likely a
      leaf from the garden) as well as a textile foreign body (probably of iatrogenic
      origin). CONCLUSION: Undiscovered foreign bodies of the main nasal cavity are a
      common cause for the formation of rhinoliths. We have also displayed the
      respective incidence and the therapeutic options.

PMID- 24932634
TI  - The wine and beer yeast Dekkera bruxellensis.
AB  - Recently, the non-conventional yeast Dekkera bruxellensis has been gaining more
      and more attention in the food industry and academic research. This yeast species
      is a distant relative of Saccharomyces cerevisiae and is especially known for two
      important characteristics: on the one hand, it is considered to be one of the
      main spoilage organisms in the wine and bioethanol industry; on the other hand,
      it is 'indispensable' as a contributor to the flavour profile of Belgium lambic
      and gueuze beers. Additionally, it adds to the characteristic aromatic properties
      of some red wines. Recently this yeast has also become a model for the study of
      yeast evolution. In this review we focus on the recently developed molecular and
      genetic tools, such as complete genome sequencing and transformation, to study
      and manipulate this yeast. We also focus on the areas that are particularly well
      explored in this yeast, such as the synthesis of off-flavours, yeast detection
      methods, carbon metabolism and evolutionary history.

PMID- 24932635
TI  - Anaphylaxis to iodinated contrast media: clinical characteristics related with
      development of anaphylactic shock.
AB  - OBJECTIVE: Anaphylaxis is the most severe form of radiocontrast media (RCM)
      induced hypersensitivity and can be life-threatening if profound hypotension is
      combined. With increased use of iodine based RCM, related hypersensitivity is
      rapidly growing. However, the clinical characteristics and risk factors of RCM
      induced anaphylaxis accompanied by hypotension (anaphylactic shock) are not
      clearly defined. This study was performed to investigate the risk factors of RCM
      induced anaphylactic shock and the clinical value of RCM skin testing to identify
      causative agents in affected patients. METHODS: We analyzed the data of RCM
      induced anaphylaxis monitored by an inhospital pharmacovigilance center at a
      tertiary teaching hospital from January 2005 to December 2012 and compared the
      clinical features and skin test results according to the accompanying
      hypotension. RESULTS: Among total of 104 cases of RCM induced anaphylaxis, 34.6%
      of patients, developed anaphylaxis on their first exposure to RCM. Anaphylactic
      patients presenting with shock were older (57.4 vs. 50.1 years, p = 0.026) and
      had a history of more frequently exposure to RCM (5.1+/-7.8 vs. 1.9+/-3.3, p =
      0.004) compared to those without hypotension. Among RCMs, hypotension was more
      frequent in anaphylaxis related to iopromide compared to other agents (85.0% vs.
      61.4%, p = 0.011). Skin tests were performed in 51 patients after development of
      RCM induced anaphylaxis. Overall skin test positivity to RCM was 64.7% and 81.8%
      in patients with anaphylactic shock. CONCLUSION: RCM induced anaphylactic shock
      is related to multiple exposures to RCM and most patients showed skin test
      positivity to RCM.

PMID- 24932636
TI  - The nuclear receptor REV-ERBalpha regulates Fabp7 and modulates adult hippocampal
      neurogenesis.
AB  - The function of the nuclear receptor Rev-erbalpha (Nr1d1) in the brain is, apart
      from its role in the circadian clock mechanism, unknown. Therefore, we compared
      gene expression profiles in the brain between wild-type and Rev-erbalpha knock
      out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a
      direct target of repression by REV-ERBalpha. Loss of Rev-erbalpha manifested in
      memory and mood related behavioral phenotypes and led to overexpression of Fabp7
      in various brain areas including the subgranular zone (SGZ) of the hippocampus,
      where neuronal progenitor cells (NPCs) can initiate adult neurogenesis. We found
      increased proliferation of hippocampal neurons and loss of its diurnal pattern in
      Rev-erbalpha KO mice. In vitro, proliferation and migration of glioblastoma cells
      were affected by manipulating either Fabp7 expression or REV-ERBalpha activity.
      These results suggest an important role of Rev-erbalpha and Fabp7 in adult
      neurogenesis, which may open new avenues for treatment of gliomas as well as
      neurological diseases such as depression and Alzheimer. 

PMID- 24932637
TI  - SemFunSim: a new method for measuring disease similarity by integrating semantic
      and gene functional association.
AB  - BACKGROUND: Measuring similarity between diseases plays an important role in
      disease-related molecular function research. Functional associations between
      disease-related genes and semantic associations between diseases are often used
      to identify pairs of similar diseases from different perspectives. Currently, it
      is still a challenge to exploit both of them to calculate disease similarity.
      Therefore, a new method (SemFunSim) that integrates semantic and functional
      association is proposed to address the issue. METHODS: SemFunSim is designed as
      follows. First of all, FunSim (Functional similarity) is proposed to calculate
      disease similarity using disease-related gene sets in a weighted network of human
      gene function. Next, SemSim (Semantic Similarity) is devised to calculate disease
      similarity using the relationship between two diseases from Disease Ontology.
      Finally, FunSim and SemSim are integrated to measure disease similarity. RESULTS:
      The high average AUC (area under the receiver operating characteristic curve)
      (96.37%) shows that SemFunSim achieves a high true positive rate and a low false
      positive rate. 79 of the top 100 pairs of similar diseases identified by
      SemFunSim are annotated in the Comparative Toxicogenomics Database (CTD) as being
      targeted by the same therapeutic compounds, while other methods we compared could
      identify 35 or less such pairs among the top 100. Moreover, when using our method
      on diseases without annotated compounds in CTD, we could confirm many of our
      predicted candidate compounds from literature. This indicates that SemFunSim is
      an effective method for drug repositioning.

PMID- 24932638
TI  - Evaluating the feasibility of an agglomerative hierarchy clustering algorithm for
      the automatic detection of the arterial input function using DSC-MRI.
AB  - During dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI), it
      has been demonstrated that the arterial input function (AIF) can be obtained
      using fuzzy c-means (FCM) and k-means clustering methods. However, due to the
      dependence on the initial centers of clusters, both clustering methods have poor
      reproducibility between the calculation and recalculation steps. To address this
      problem, the present study developed an alternative clustering technique based on
      the agglomerative hierarchy (AH) method for AIF determination. The performance of
      AH method was evaluated using simulated data and clinical data based on
      comparisons with the two previously demonstrated clustering-based methods in
      terms of the detection accuracy, calculation reproducibility, and computational
      complexity. The statistical analysis demonstrated that, at the cost of a
      significantly longer execution time, AH method obtained AIFs more in line with
      the expected AIF, and it was perfectly reproducible at different time points. In
      our opinion, the disadvantage of AH method in terms of the execution time can be
      alleviated by introducing a professional high-performance workstation. The
      findings of this study support the feasibility of using AH clustering method for
      detecting the AIF automatically. 

PMID- 24932640
TI  - Psychometric properties of abbreviated and ultra-brief versions of the Penn State
      Worry Questionnaire.
AB  - The Penn State Worry Questionnaire (PSWQ) is a 16-item self-report measure
      considered the gold-standard assessment instrument for worry. Two abbreviated
      versions of the PSWQ have also been developed. An 8-item measure (PSWQ-A) was
      designed to address poor model fit of the full version with older adult samples,
      and a 3-item version (PSWQ-3) was developed in a clinical setting to avoid
      problems related to the reverse-scored items and to increase clinical utility.
      Preliminary examinations of the abbreviated forms have been promising, but
      additional psychometric evaluation is needed to confirm their reliability and
      validity. The current study compared psychometric properties of the 3 versions of
      the PSWQ in a heterogeneous clinical sample of 272 patients presenting for
      treatment in a partial hospital setting. Results suggested that scores for all 3
      versions had good internal consistency; convergent validity with anxiety, stress,
      intolerance of uncertainty, negative problem orientation, and negative beliefs
      about worry; as well as adequate discriminant validity with depression, emotional
      lability, and substance abuse. On all 3 versions, individuals with generalized
      anxiety disorder (GAD) scored higher than those without the disorder, and across
      all participants, scores decreased from pre- to posttreatment. Finally, scores on
      the 3 versions showed similar levels of sensitivity and specificity as screening
      tools for GAD. Overall, the PSWQ-A and PSWQ-3 scores appear to be internally
      consistent and valid measures of worry that performed similarly to the full 16
      item PSWQ. Given the strong psychometric properties of the shorter form scores,
      clinicians may prefer such forms, as they are quick to administer and easy to
      score in session.

PMID- 24932639
TI  - The quaternary lidocaine derivative QX-314 produces long-lasting intravenous
      regional anesthesia in rats.
AB  - BACKGROUND: The lidocaine derivative, QX-314, produces long-lasting regional
      anesthesia in various animal models. We designed this study to examine whether QX
      314 could produce long-lasting intravenous regional anesthesia (IVRA) in a rat
      model. METHODS: IVRA was performed on tail of rats. EC50 (median effective
      concentration) of QX-314 in IVRA was determined by up-and-down method. IVRA on
      tail of rats was evaluated by tail-flick and tail-clamping tests. For comparison
      between QX-314 and lidocaine, 60 Sprague-Dawley rats were randomly divided into 6
      groups (n = 10/group), respectively receiving 0.5 ml of 0.5% lidocaine, 0.25% QX
      314, 0.5% QX-314, 1.0% QX-314, 2.0% QX-314 and normal saline. To explore the role
      of TRPV1 channel in IVRA of QX-314, 20 rats were randomly divided into 2 groups
      (n = 10/group), respectively receiving 0.5 ml of 1% QX-314 and 1% QX-314+75 ug/ml
      capsazepine. Toxicities of QX-314 on central nervous system and cardiac system
      were measured in rats according to Racine's convulsive scale and by
      electrocardiogram, respectively. RESULTS: QX-314 could produce long-lasting IVRA
      in a concentration-dependent manner. EC50 of QX-314 in rat tail IVRA was 0.15 +/-
      0.02%. At concentration of 0.5%, IVRA duration of QX-314 (2.5 +/- 0.7 hour) was
      significantly longer than that of 0.5% lidocaine (0.3 +/- 0.2 hour, P<0.001).
      TRPV1 channel antagonist (capsazepine) could significantly reduce the effect of
      QX-314. For evaluation of toxicities, QX-314 at doses of 5 or 10 mg/kg did not
      induce any serious complications. However, QX-314 at dose of 20 mg/kg (1% QX-314
      0.5 ml for a rat weighing 250 g) induced death in 6/10 rats. CONCLUSIONS: QX-314
      could produce long-lasting IVRA in a concentration-dependent manner. This long
      lasting IVRA was mediated by activation of TRPV1 channels. Evaluation of toxic
      complications of QX-314 confirmed that low but relevant doses of QX-314 did not
      result in any measurable toxicity.

PMID- 24932641
TI  - Development and validation of the Peer Interaction Macro-Coding System Scales
      (PIMS): a new tool for observational measurement of social competence in youth
      with spina bifida.
AB  - Many children with chronic health conditions encounter enduring difficulties in
      their peer interactions and friendships. This study aimed to create and validate
      scales derived from an observational coding system (i.e., Peer Interaction Macro
      Coding System, or PIMS) in a sample of children with spina bifida and their
      peers. Participants were 106 target child-peer dyads who completed a battery of
      questionnaires and interviews and were videotaped performing 4 interaction tasks,
      which were then coded across multiple domains of social functioning. Five scales
      (i.e., Control, Prosocial Skills, Positive Affect, Conflict, and Dyadic Cohesion)
      were rationally derived based on a review of the literature and a panel of
      experts. Internal consistency and interrater reliability at the scale level were
      good to excellent for all 5 scales. Interscale correlations were in the low-to
      moderate range for 4 of the scales, although the Dyadic Cohesion Scale was highly
      correlated with two other scales and was subsequently dropped. Convergent
      validity and discriminant validity were established by examining the 4 remaining
      scales in association with comparable questionnaire and interview data. The 4
      PIMS scales appear to be reliable and valid measures of social competence and may
      enhance future multimethod research efforts aimed at learning more about peer
      interactions and overall social competence.

PMID- 24932643
TI  - A test of the International Personality Item Pool representation of the Revised
      NEO Personality Inventory and development of a 120-item IPIP-based measure of the
      five-factor model.
AB  - There has been a substantial increase in the use of personality assessment
      measures constructed using items from the International Personality Item Pool
      (IPIP) such as the 300-item IPIP-NEO (Goldberg, 1999), a representation of the
      Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992). The IPIP-NEO
      is free to use and can be modified to accommodate its users' needs. Despite the
      substantial interest in this measure, there is still a dearth of data
      demonstrating its convergence with the NEO PI-R. The present study represents an
      investigation of the reliability and validity of scores on the IPIP-NEO.
      Additionally, we used item response theory (IRT) methodology to create a 120-item
      version of the IPIP-NEO. Using an undergraduate sample (n = 359), we examined the
      reliability, as well as the convergent and criterion validity, of scores from the
      300-item IPIP-NEO, a previously constructed 120-item version of the IPIP-NEO
      (Johnson, 2011), and the newly created IRT-based IPIP-120 in comparison to the
      NEO PI-R across a range of outcomes. Scores from all 3 IPIP measures demonstrated
      strong reliability and convergence with the NEO PI-R and a high degree of
      similarity with regard to their correlational profiles across the criterion
      variables (rICC = .983, .972, and .976, respectively). The replicability of these
      findings was then tested in a community sample (n = 757), and the results closely
      mirrored the findings from Sample 1. These results provide support for the use of
      the IPIP-NEO and both 120-item IPIP-NEO measures as assessment tools for
      measurement of the five-factor model.

PMID- 24932642
TI  - Temporal stability of DSM-5 posttraumatic stress disorder criteria in a problem
      drinking sample.
AB  - The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      5) reformulated posttraumatic stress disorder (PTSD) based partially on research
      showing there were 4 main factors that underlie the symptoms of the disorder. The
      primary aim of this study was to examine the temporal stability of the DSM-5
      factors as measured by the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL
      5; Weathers et al., 2010). Confirmatory factor analyses were conducted to examine
      the structure of DSM-5 PTSD, and temporal stability over 3 time points was
      examined to determine if the measure reflects a consistent construct over time.
      Our sample was 507 combat-exposed veterans of Iraq and Afghanistan who enrolled
      in an online intervention for problem drinking and combat-related stress (Brief
      et al., 2013). We administered the PCL-5 at baseline, 8-week postintervention,
      and 3-month follow-up assessments. The DSM-5 model provided an adequate fit to
      the data at baseline. Tests of equality of form and equality of factor loadings
      demonstrated stability of the factor structure over time, indicating temporal
      stability. This study confirmed the results of previous research supporting the
      DSM-5 model of PTSD symptoms (Elhai et al., 2012; Miller et al., 2013). This is
      the 1st study to demonstrate the temporal stability of the PCL-5, indicating its
      use in longitudinal studies measures the same construct over time.

PMID- 24932644
TI  - Ratings of ADHD symptoms and academic impairment by mothers, fathers, teachers,
      and aides: construct validity within and across settings as well as occasions.
AB  - A Multiple Indicator * Multiple Trait * Multiple Source * Multiple Occasion
      design was used to evaluate invariance, convergent and discriminant validity of
      ADHD-inattention (IN), ADHD-hyperactivity/impulsivity (HI), and academic
      impairment scores from the Child and Adolescent Disruptive Behavior Inventory
      (CADBI) using confirmatory factor analysis. Mothers, fathers, teachers, and aides
      completed the CADBI on 811 Spanish 1st-grade children (54% boys) twice (6-week
      separation). For mothers and fathers, like loadings, thresholds/intercepts,
      factor means, factor variances, and factor covariances/correlations were
      invariant across sources and occasions. All 3 factors also showed convergent
      (convergent correlations from .69 to .83) and significant discriminant validity.
      For teachers and aides, there was also invariance of parameters along with
      convergent and discriminant validity over sources and occasions (convergent
      correlations from .67 to .87). With construct validity established for home and
      school, it was meaningful to test construct validity between home and school.
      Like-item loadings and thresholds/intercepts were invariant between home and
      school, with the ADHD-HI factor mean being lower at school. Convergent validity
      of ADHD-IN, ADHD-HI, and academic impairment factors, especially ADHD-IN and ADHD
      HI, was much weaker between home and school (convergent correlations from .36 to
      .47 for IN and HI). The strong convergent validity of ADHD-IN and ADHD-HI scores
      within home and school in conjunction with weak convergent validity across home
      and school has implications for the assessment and diagnosis of ADHD (i.e., the
      diagnostic criteria of symptom occurrence in 2 or more settings).

PMID- 24932645
TI  - Resilience in a sample of Mexican American adolescents with substance use
      disorders.
AB  - Resolving the many tasks of adolescent development requires resilience. However,
      understanding the role that resilience plays in adolescent development involves
      adequate measurement of the construct. The Connor-Davidson Resilience Scale (CD
      RISC) is a widely used measure of resilience, but a stable latent factor
      structure has not been identified across studies. The measure has typically been
      examined in adult samples while little attention has been given to its use with
      adolescents in general and ethnic minority adolescents in particular. The primary
      purpose of the current study is to identify a latent factor structure of the CD
      RISC in a sample of primarily Mexican American adolescents (N = 106). Two
      competing model structures were tested via confirmatory factor analysis and
      results supported a 7-item unidimensional factor model. Support was also found
      for the construct validity of the measure in relation to ethnic identity and
      depressive symptoms for adolescents in this sample. Implications of the study
      findings for adolescents and avenues of future research are discussed.

PMID- 24932646
TI  - Factor structure and diagnostic validity of the Beck Depression Inventory-II with
      adult clinical inpatients: comparison to a gold-standard diagnostic interview.
AB  - Little is known about the psychometric properties and clinical utility of the
      Beck Depression Inventory-II (BDI-II) among adult clinical inpatients, a group at
      high risk for major depressive disorder (MDD). Data from 1,904 adult inpatients
      were analyzed using confirmatory factor analysis (CFA), Cronbach's alpha, and
      Pearson's correlations. Receiver operating characteristic (ROC) analyses
      evaluating MDD diagnostic performance were conducted with a subsample (n = 467)
      using a structured diagnostic interview for reference. CFA of 3 previous 2-factor
      oblique solutions, observed in adolescent and older adult inpatient clinical
      samples, and 3 corresponding bifactor solutions indicated that BDI-II common item
      variance was overwhelmingly accounted for by 1 general factor specified to all
      items, with minor additional variance contributed by 2 specific factors. Analyses
      revealed high internal consistency (Cronbach's alpha = .93) and significant (p <
      .01) intercorrelations between the BDI-II total scale and Behavior and Symptom
      Identification Scale-24's Depression/Functioning (r = .79) and Overall (r = .82)
      subscales. ROC analyses generated low area under the curve (.695; 95% confidence
      interval [.637, .752]) and cutoff scores with poor sensitivity/specificity
      balance. BDI-II use as a screening instrument for overall depressive symptomology
      was supported, but MDD diagnostic performance was suboptimal. Clinicians are
      advised to use the BDI-II to gauge severity of depression and measure clinical
      changes to depressive symptomology over time but to be mindful of the limitations
      of the BDI-II as a diagnostic tool for adult inpatients.

PMID- 24932647
TI  - Does field reliability for Static-99 scores decrease as scores increase?
AB  - This study examined the field reliability of Static-99 (Hanson & Thornton, 2000)
      scores among 21,983 sex offenders and focused on whether rater agreement
      decreased as scores increased. As expected, agreement was lowest for high-scoring
      offenders. Initial and most recent Static-99 scores were identical for only about
      40% of offenders who had been assigned a score of 6 during their initial
      evaluations, but for more than 60% of offenders who had been assigned a score of
      2 or lower. In addition, the size of the difference between scores increased as
      scores increased, with pairs of scores differing by 2 or more points for about
      30% of offenders scoring in the high-risk range. Because evaluators and systems
      use high Static-99 scores to identify sexual offenders who may require intensive
      supervision or even postrelease civil commitment, it is important to recognize
      that there may be more measurement error for high scores than low scores and to
      consider adopting procedures for minimizing or accounting for measurement error.
      (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24932648
TI  - Comparing short forms of the Social Interaction Anxiety Scale and the Social
      Phobia Scale.
AB  - The Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS;
      Mattick & Clarke, 1998) are companion scales developed to measure anxiety in
      social interaction and performance situations, respectively. The measures have
      strong discriminant and convergent validity; however, their factor structures
      remain debated, and furthermore, the combined administration length (i.e., 39
      items) can be prohibitive for some settings. There have been 4 attempts to assess
      the factor structures of the scales and reduce the item content: the 14-item
      Social Interaction Phobia Scale (SIPS; Carleton et al., 2009), the 12-item SIAS
      6/SPS-6 (Peters, Sunderland, Andrews, Rapee, & Mattick, 2012), the 21-item
      abbreviated SIAS/SPS (ASIAS/ASPS; Kupper & Denollet, 2012), and the 12-item
      Readability SIAS and SPS (RSIAS/RSPS; Fergus, Valentiner, McGrath, Gier-Lonsway,
      & Kim, 2012). The current study compared the short forms on (a) factor structure,
      (b) ability to distinguish between clinical and non-clinical populations, (c)
      sensitivity to change following therapy, and (d) convergent validity with related
      measures. Participants included 3,607 undergraduate students (55% women) and 283
      patients with social anxiety disorder (43% women). Results of confirmatory factor
      analyses, sensitivity analyses, and correlation analyses support the robust
      utility of items in the SIPS and the SPS-6 and SIAS-6 relative to the other short
      forms; furthermore, the SIPS and the SPS-6 and SIAS-6 were also supported by
      convergent validity analyses within the undergraduate sample. The RSIAS/RSPS and
      the ASIAS/ASPS were least supported, based on the current results and the
      principle of parsimony. Accordingly, researchers and clinicians should consider
      carefully which of the short forms will best suit their needs.

PMID- 24932649
TI  - The influence of contextual information on lay judgments of childhood mental
      health concerns.
AB  - Decisions about whether a person is in need of mental health care are often made
      by laypeople with no training in the identification of mental health concerns.
      For example, the parent of a child displaying problematic behavior has to decide
      whether this behavior is likely related to mental health concerns and
      necessitates professional care. The process of identifying mental health concerns
      is made more complicated by the rich background of real-world environmental
      factors or contexts in which concerns can present-contexts that might or might
      not relate to the presence of mental health concerns. We investigated whether
      laypeople use contextual information to make judgments regarding childhood mental
      health disorder symptoms. In Experiment 1, we demonstrated that laypeople's
      judgments of the likelihood of a mental disorder are influenced by non-diagnostic
      contextual information that surrounds symptoms of the disorder. In Experiment 2,
      we demonstrated that providing a causal origin for such disorder symptoms
      accentuates the use of context, regardless of the nature of the causal process
      (i.e., environmental vs. biological). These findings indicate that contextual
      influences on judgments about mental health concerns may reflect a more general
      set of mental reasoning processes than indicated by previous work focused on
      clinicians' judgments. Consequently, these findings have important implications
      for how we think about the influence of contextual information on decision making
      more generally as well as for improving our ability to both reliably identify
      children in need of mental health care and increase children's access to such
      care.

PMID- 24932651
TI  - The use of assistive technology in the everyday lives of young people living with
      dementia and their caregivers. Can a simple remote control make a difference?
AB  - BACKGROUND: This study was a part of a larger study exploring the impact of
      assistive technology on the lives of young people living with dementia (YPD).
      This paper focuses on one of the most useful devices, the simple remote control
      (SRC). The objective was to explore the reason why the SRC is significant and
      beneficial in the everyday lives of YPD and their caregivers. METHODS: This
      qualitative longitudinal study had a participatory design. Eight participants
      received an SRC. The range for using it was 0-15 months. In-depth interviews and
      observations were conducted at baseline and repeated every third month up to 18
      months. A situated learning approach was used in the analysis to provide a deeper
      understanding of the significance and use of SRC. RESULTS: Young people having
      dementia spend a substantial amount of time alone. Watching television was
      reported to be important, but handling remote controls was challenging and
      created a variety of problems. YPD learned to use SRC, which made important
      differences in the everyday lives of all family members. Comprehensive support
      from caregivers and professionals was important for YPD in the learning process.
      CONCLUSIONS: The SRC was deemed a success because it solved challenges regarding
      the use of television in everyday lives of families. The design was recognizable
      and user-friendly, thus allowing YPD to learn its operation. Access to
      professional support and advice regarding assistive technology is vital for
      establishing a system for follow-up and continued collaboration to make future
      adaptations and adjustments.

PMID- 24932652
TI  - Endosonography-guided drainage of malignant fluid collections using lumen
      apposing, fully covered self-expanding metal stents.
AB  - Endosonography (EUS)-guided drainage of paragastric fluid collections using fully
      covered self-expanding metal stents (FCSEMS) is now a well-established procedure.
      Recently, new and specially designed lumen-apposing, fully-covered metal
      cystgastrostomy stents have been employed for this indication. In this case
      series, the use of these new stents for the drainage of malignant fluid
      collections in three symptomatic patients is described. Cases included a large
      pancreatic pseudocyst, secondary to underlying acute lymphoblastic leukemia, and
      two large collections of loculated ascites due to metastatic ovarian and cervical
      cancer, respectively. Technical success in inserting the new stents was achieved
      in all three patients, and resulted in symptomatic relief. There were no
      clinically significant complications directly attributed to the stents. These new
      lumen-apposing cystgastrostomy stents may provide a viable, minimally invasive,
      and effective alternative for drainage of malignant fluid collections, either for
      definitive treatment or for palliation of symptoms. 

PMID- 24932650
TI  - Development and validation of the Hookup Motives Questionnaire (HMQ).
AB  - Despite the high prevalence rates and growing research on hooking up among
      college students, no multidimensional inventory exists in the literature to
      assess motivations for hooking up. In the current study, we report on the
      development and validation of the Hookup Motives Questionnaire (HMQ), designed to
      assess the various reasons for hooking up. Exploratory and confirmatory factor
      analyses were conducted using 2 samples of college students (Campus 1, N = 401;
      Campus 2, N = 367). Exploratory factor analysis was undertaken to explore the
      psychometric properties of an initial set of 25 items, and confirmatory factor
      analysis was conducted to evaluate additional properties of the factor structure.
      The final factor structure of the HMQ contained 19 items that tapped 5 subscales
      representing social-sexual, social-relationship, enhancement, coping, and
      conformity motives. Results demonstrated good internal consistency and
      discriminant validity for the subscales. Moreover, criterion-related validity was
      satisfied by showing that HMQ subscales significantly correlated with hookup
      approval and behavior. Gender differences on the measures were found. The
      inventory offers considerable potential as a psychometrically sound instrument
      that may be administered to understand reasons for engaging in potentially risky
      hookup behaviors and used to inform the design of sexual health programs and
      interventions targeting young adults.

PMID- 24932653
TI  - The diagnosis and management of common sleep disorders in adolescents.
AB  - PURPOSE OF REVIEW: Sleep problems in adolescents are very common and negatively
      impact the quality of their health and lives, yet often go undiagnosed. This
      review is meant to familiarize pediatricians with some of the more commonly
      encountered sleep disorders in this age group, and to review their diagnosis and
      management. RECENT FINDINGS: Recent findings reinforce the ubiquity of
      insufficient and poor-quality sleep in teens and their consequences on physical
      and mental health, cognition, and behavior. Increasing use of technology by
      teens, especially at night, plays a growing role in this. Parentally set bedtimes
      can be effective in increasing the sleep duration, thereby diminishing the
      consequences of insufficient sleep. Parasomnias, common in early childhood,
      usually diminish with the transition into adolescence. An almost 10-fold increase
      in the incidence of narcolepsy has been reported following the use of one type of
      vaccination against influenza H1N1 in Europe. Recent guidelines for the diagnosis
      and management of obstructive sleep apnea are reviewed, as are recent guidelines
      pertaining to the management of sleep disorders of children on the autism
      spectrum. SUMMARY: Sleep disorders in adolescents are both very common and
      underdiagnosed, adversely affecting their overall well being.

PMID- 24932655
TI  - Closure technique for labyrinthine fistula by "underwater" endoscopic ear
      surgery.

PMID- 24932654
TI  - The involvement of MiR-1-clathrin pathway in the regulation of phagocytosis.
AB  - Phagocytosis, one of the most powerful immune responses, is a complicated process
      regulated by many factors. However the regulation of phagocytosis mediated by
      microRNAs has not been extensively investigated. To address this issue, the
      regulation of phagocytosis by miR-1 was characterized in this study. The results
      showed that miR-1 played an important role in the phagocytosis regulation in
      shrimp in vivo. The sequence analysis indicated that miR-1 was highly conserved
      from invertebrates to mammals, suggesting that miR-1 might share the similar or
      same functions in phagocytosis of shrimp hemocytes and mammalian macrophages. The
      data presented that miR-1 was significantly downregulated in cancerous macrophage
      RAW264.7 cells compared with those in the isolated murine macrophage and in the
      immortalized macrophage ANA-1. The findings showed that miR-1 had a great effect
      on the regulation of phagocytosis in cancerous macrophage by the inhibition of
      clathrin heavy chain 1 (CLTC1) gene. Therefore our study presented a novel miR-1
      mediated regulation of phagocytosis both in invertebrate and in vertebrate. 

PMID- 24932656
TI  - Effect of instant cooked giant embryonic rice on body fat weight and plasma lipid
      profile in high fat-fed mice.
AB  - The comparative effects of instant cooked rice made from giant embryo mutant or
      ordinary normal rice on body weight and lipid profile in high fat-fed mice were
      investigated. The animals were given experimental diets for seven weeks: normal
      control (NC), high fat (HF), and HF supplemented with instant normal white (HF
      NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic
      brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat,
      plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic
      index relative to NC group. However, instant rice supplementation counteracted
      this high fat-induced hyperlipidemia through regulation of lipogenesis and
      adipokine production. The GB rice exhibited greater hypolipidemic and body fat
      lowering effects than the GW or NB rice. These findings illustrate that the giant
      embryo mutant may be useful as functional biomaterial for the development of
      instant rice with strong preventive action against high fat diet-induced
      hyperlipidemia and obesity. 

PMID- 24932658
TI  - Hand movements reflect competitive processing in numerical cognition.
AB  - Traditional models of numerical cognition are based on the computer-based
      metaphor of cognition that assumes numerical judgments are stage-based and
      independent of bodily effectors. However, recent studies have indicated that the
      traditional metaphor may be inadequate for describing the processes involved in
      numerical decisions. In the present study, I provide further evidence that number
      processing proceeds in a continuous, competitive manner tightly coupled with
      feedback from the motor system. Forty-five adult participants' hand movements
      were recorded as they used a computer mouse to choose the correct parity
      (odd/even) for single-digit numerals. Distributional analyses of these hand
      movements indicated that responses resulted from competition between parallel and
      partially active mental representations rather than occurring in discrete stages.

PMID- 24932657
TI  - Bioavailability of zinc in Wistar rats fed with rice fortified with zinc oxide.
AB  - The study of zinc bioavailability in foods is important because this mineral
      intake does not meet the recommended doses for some population groups. Also, the
      presence of dietary factors that reduce zinc absorption contributes to its
      deficiency. Rice fortified with micronutrients (Ultra Rice(r)) is a viable
      alternative for fortification since this cereal is already inserted into the
      population habit. The aim of this study was to evaluate the bioavailability of
      zinc (Zn) in rice fortified with zinc oxide. During 42 days, rats were divided
      into four groups and fed with diets containing two different sources of Zn (test
      diet: UR(r) fortified with zinc oxide, or control diet: zinc carbonate (ZnCO3)),
      supplying 50% or 100%, respectively, of the recommendations of this mineral for
      animals. Weight gain, food intake, feed efficiency ratio, weight, thickness and
      length of femur; retention of zinc, calcium (Ca) and magnesium (Mg) in the femur
      and the concentrations of Zn in femur, plasma and erythrocytes were evaluated.
      Control diet showed higher weight gain, feed efficiency ratio, retention of Zn
      and Zn concentration in the femur (p < 0.05). However, no differences were
      observed (p > 0.05) for dietary intake, length and thickness of the femur,
      erythrocyte and plasmatic Zn between groups. Although rice fortified with zinc
      oxide showed a lower bioavailability compared to ZnCO3, this food can be a viable
      alternative to be used as a vehicle for fortification. 

PMID- 24932659
TI  - The evaluation of readiness of medical personnel to act under conditions of
      chemical contamination.
AB  - OBJECTIVE: We evaluated the knowledge of physicians, nurses, and paramedics in
      Poland about the procedures in a chemical contamination. METHODS: An anonymous
      survey was mailed to 600 randomly selected physicians, nurses, and paramedics.
      The survey included questions concerning the process of decontamination,
      knowledge of toxidromes, and the use of selected antidotes. RESULTS: Completed
      surveys were received from 510 respondents (85%). A very low level of knowledge
      was observed regarding decontamination techniques (from 8.3% to 34.2%), use of
      antidotes (from 13.7% to 61%), and knowledge of toxidromes (from 10.2% to 22.7%).
      CONCLUSIONS: Our findings showed that for all aspects of chemical rescue
      procedures queried, the knowledge of medical personnel was not satisfactory. Both
      practical and theoretical training of medical personnel is urgently needed for
      life-saving procedures during a chemical contamination.

PMID- 24932660
TI  - The synergistic effect of nanotopography and sustained dual release of
      hydrophobic and hydrophilic neurotrophic factors on human mesenchymal stem cell
      neuronal lineage commitment.
AB  - A combination of nanotopography and controlled release is a potential platform
      for neuronal tissue engineering applications. Previous studies showed that
      combining both physical and chemical guidance was more effective than individual
      cues in the directional promotion of neurite outgrowth. Nanotopography can direct
      human mesenchymal stem cells (hMSCs) into neuronal lineage, while controlled
      release of neurotrophic factors can deliver temporally controlled biochemical
      signals. Hypothesizing that the synergistic effect will enhance neuronal lineage
      commitment of hMSCs, a fabrication method for multiple neurotrophic factors
      delivery from a single nanopatterned (350 nm gratings), poly-E-caprolactone (PCL)
      film was developed and evaluated. Our results showed a synergistic effect on hMSC
      differentiation cultured on substrates with both nanotopographical and
      biochemical cues. The protein/drug encapsulation into PCL nanopatterned films was
      first optimized using a hydrophilic model protein, bovine serum albumin. The
      hydrophobic retinoic acid (RA) molecule was directly incorporated into PCL films.
      To achieve sustained release, hydrophilic nerve growth factor (NGF) was first
      encapsulated within polyelectrolyte complexation fibers before they were embedded
      within the nanopatterned PCL film. Our results showed that nanotopography on the
      fabricated polymer films remained intact, while release of bioactive RA and NGF
      was sustained over a period of 3 weeks. Under the combinatorial effect of
      physical and biochemical cues, we observed an enhanced upregulation of neuronal
      genes such as microtubule-associated protein 2 (MAP2) and neurofilament light
      (NFL) as compared with sustained delivery of individual cues and bolus delivery.
      Quantitative polymerase chain reaction analysis showed that MAP2 and NFL gene
      upregulation in hMSCs was most pronounced on the nanogratings with sustained
      release of both RA and NGF. The fabricated platforms supported the sustained
      delivery of multiple neurotrophins, including both hydrophobic and hydrophilic
      therapeutic agents, while providing surface patterning versatility for
      application in neural regeneration and tissue engineering. 

PMID- 24932661
TI  - Elevated adropin: a candidate diagnostic marker for myocardial infarction in
      conjunction with troponin-I.
AB  - Myocardial infarction (MI; "heart attack") can cause injury to or death of heart
      muscle tissue (myocardium) owing to prolonged ischemia and hypoxia. Troponins and
      CK-MB are released from heart muscle cells during MI. It has been demonstrated
      that energy expenditure is regulated by adropin expressed in the endocardium,
      myocardium, and epicardium. We hypothesized that adropin is released into the
      bloodstream during myocardial muscle injury caused by MI, so the serum level
      rises as myocytes die. Therefore, we examined the association between adropin
      expression and myocardial infarction in isoproterenol-induced myocardial
      infarction. Rats were randomly allocated to six groups. After treatment they were
      decapitated and their blood and tissues were collected for adropin measurement.
      Changes in adropin synthesis in rat heart, kidney and liver tissues in
      isoproterenol (ISO)-induced MI were demonstrated immunohistochemically. Serum
      adropin concentrations were measured by ELISA, and troponin-I, CK and CK-MB
      concentrations by autoanalysis. The results demonstrated that cardiac muscle
      cells, glomerular, peritubular and renal cortical interstitial cells, hepatocytes
      and liver sinusoidal cells all synthesize adropin, and synthesis increased 1-24 h
      after MI except in the liver cells. The findings elucidate the pathogenesis of
      MI, and the gradual increase in serum adropin could be a novel diagnostic marker
      and serve as an alternative to troponin-I measurement for diagnosing MI.

PMID- 24932663
TI  - Citrus fruit intake and bladder cancer risk: a meta-analysis of observational
      studies.
AB  - Epidemiological studies have investigated the association between citrus fruit
      and bladder cancer risk; however, the results are inconsistent. To assess these
      issues, we conducted a meta-analysis of currently available studies. We
      identified relevant articles by searching the MEDLINE and EMBASE databases. We
      calculated the summary relative risk (RR) with 95% confidence interval (95% CI)
      using a random effect model. We included eight case-control studies and six
      cohort studies in the meta-analysis. There was a significant inverse association
      between citrus fruit intake and bladder cancer risk in all pooled studies (RR:
      0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92),
      but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest
      that citrus fruit intake is related to decreased bladder cancer risk. Subsequent
      well-designed, large prospective studies are needed to obtain better
      understanding of this relationship.

PMID- 24932664
TI  - Is the red cell distribution width strong predictor for treatment response in
      primary glomerulonephritides?
AB  - BACKGROUND: Novel biomarkers are needed to predict the response to treatment in
      patients with nephrotic syndrome (NS) due to primary glomerulonephritides (PGN).
      We aimed to test the predictive value of red blood cell distribution width (RDW)
      for estimation of response to therapy in adult patients with NS. Study design,
      setting & participants, and intervention: We performed a prospective study
      including 176 patients with NS due to PGN. Patients were divided into three
      groups according to their response to the treatment. Group 1 was composed of
      patients with complete remission whereas group 2 was composed of patients with
      partial remission and group 3 was composed of patients who were resistant to the
      treatment. RESULTS: The highest baseline mean RDW value was found in group 3
      patients (17.8 +/- 1.8) whereas the lowest in group 1 (13.4 +/- 0.7) before
      treatment (p<0.05). We found a significant decrease in RDW value after an
      effective treatment in groups 1 and group 2 (p<0.05). However, there was no
      significant change in RDW values after treatment in group 3 (p>0.05). Most of the
      patient with complete remission had base-line RDW level <= 14% (n=45, 90%)
      (p<0.001, Kendal Tau: -0.86), and most of the patients who were resistant to the
      treatment had base-line RDW level p>15% (n=68, 86.1%) (p<0.001, Kendal Tau: 
      0.87). CONCLUSION: Our results suggest that pre-treatment RDW value is a
      promising novel biomarker for predicting response to the treatment in adult
      patients with NS due to PGN.

PMID- 24932666
TI  - Stability of the southern European border of Echinococcus multilocularis in the
      Alps: evidence that Microtus arvalis is a limiting factor.
AB  - SUMMARY The known range of the zoonotic fox tapeworm Echinococcus multilocularis
      has expanded since the 1990s, and today this parasite is recorded in higher
      abundances throughout large parts of Europe. This phenomenon is mostly attributed
      to the increasing European fox populations and their invasion of urban habitats.
      However, these factors alone are insufficient to explain the heterogeneous
      distribution of the parasite in Europe. Here, we analysed the spatial
      interrelationship of E. multilocularis with the known distribution of seven vole
      species in Ticino, southern Switzerland. Among 404 necropsied foxes (1990-2006)
      and 79 fox faecal samples (2010-2012), E. multilocularis was consistently found
      in the north of the investigated area. No expansion of this endemic focus was
      recorded during the 22 years of the study period. This stable endemic focus is
      coincident with the known distribution of the vole species Microtus arvalis but
      not, or only partly, with the distribution of the other autochthonous vole
      species. Our results give evidence that this vole species plays a crucial role in
      the maintenance of the parasite's life cycle and that its absence could be a
      limiting factor for the spread of E. multilocularis in this region.

PMID- 24932665
TI  - Interplay between HDAC6 and its interacting partners: essential roles in the
      aggresome-autophagy pathway and neurodegenerative diseases.
AB  - Cytoplasmic localization and possession of two deacetylase domains and a
      ubiquitin-binding domain make histone deacetylase 6 (HDAC6) a unique histone
      deacetylase. HDAC6 interacts with a number of proteins in the cytoplasm. Some of
      these proteins can be deacetylated by HDAC6 deacetylase activity. Others can
      affect HDAC6 functions by modulating its catalytic activity or ubiquitin-binding
      capability. Over the last decade, HDAC6 has been shown to play important roles in
      the aggresome-autophagy pathway, which selectively targets on protein aggregates
      or damaged organelles for their accumulation and clearance in cells. HDAC6
      interacting partners are integral components in this pathway with regard to their
      regulatory roles through interaction with HDAC6. The aggresome-autophagy pathway
      appears to be an attractive therapeutic target for the treatment of
      neurodegenerative diseases as accumulation of protein aggregates are hallmarks in
      these diseases. In the current review, I discuss the molecular details of how
      HDAC6 and its interacting partners regulate each individual step in the aggresome
      autophagy pathway and also provide perspectives of how HDAC6 can be targeted in
      treating neurodegenerative diseases. 

PMID- 24932667
TI  - Rh-catalyzed sequential oxidative C-H and N-N bond activation: conversion of
      azines into isoquinolines with air at room temperature.
AB  - A rhodium-catalyzed sequential oxidative C-H annulation reaction between
      ketazines and internal alkynes has been developed via C-H and N-N bond activation
      with air as an external oxidant, which led to an efficient approach toward
      isoquinolines with high atom efficiency at rt. Utilizing the distinctive
      reactivity of this catalysis, both N-atoms of the azines could be efficiently
      incorporated to the desired isoquinolines under very robust and mild reaction
      conditions. 

PMID- 24932668
TI  - Design and characterization of a synthetically accessible, photodegradable
      hydrogel for user-directed formation of neural networks.
AB  - Hydrogels with photocleavable units incorporated into the cross-links have
      provided researchers with the ability to control mechanical properties temporally
      and study the role of matrix signaling on stem cell function and fate. With a
      growing interest in dynamically tunable cell culture systems, methods to
      synthesize photolabile hydrogels from simple precursors would facilitate broader
      accessibility. Here, a step-growth photodegradable poly(ethylene glycol) (PEG)
      hydrogel system cross-linked through a strain promoted alkyne-azide cycloaddition
      (SPAAC) reaction and degraded through the cleavage of a nitrobenzyl ether moiety
      integrated into the cross-links is developed from commercially available
      precursors in three straightforward synthetic steps with high yields (>95%). The
      network evolution and degradation properties are characterized in response to one
      and two-photon irradiation. The PEG hydrogel is employed to encapsulate
      embryonic stem cell-derived motor neurons (ESMNs), and in situ degradation is
      exploited to gain three-dimensional control over the extension of motor axons
      using two-photon infrared light. Finally, ESMNs and their in vivo synaptic
      partners, myotubes, are coencapsulated, and the formation of user-directed neural
      networks is demonstrated. 

PMID- 24932670
TI  - Continuous Infusion of Ketamine for Out-of-hospital Isolated Orthopedic Injuries
      Secondary to Trauma: A Randomized Controlled Trial.
AB  - Abstract Objective. Although ketamine has recently been demonstrated to provide a
      morphine-sparing effect, no previous study reports the effect of continuous
      infusion of ketamine for analgesia in out-of-hospital environments. The aim of
      this study was to compare the effect of a continuous infusion of ketamine (IK
      group) vs. a continuous infusion of saline (IS group) on morphine requirements in
      out-of-hospital trauma patients suffering from severe acute pain. Methods. In
      this prospective, multicenter, randomized, single-blind clinical study, patients
      suffering from isolated orthopedic injuries secondary to trauma with severe acute
      pain received a low-dose intravenous (IV) bolus of ketamine (0.2 mg.kg-1)
      combined with an IV bolus of morphine (0.1 mg.kg-1) and were randomized either in
      the IK group (IV continuous infusion of ketamine 0.2 mg.kg-1.h-1), or in the IS
      group (IV continuous infusion of saline at the same volume). The primary endpoint
      was morphine requirements in terms of total dose of morphine (excluding the
      baseline bolus) injected at the end of prehospital emergency care at hospital
      admission (final time, Tf). The secondary endpoint was evaluation of pain with
      visual analogic scale (VAS). Results. Sixty-six patients were enrolled. Total
      morphine dose was not significantly reduced with continuous infusion of ketamine
      (0.048 [0.000; 0.150] vs. 0.107 [0.052; 0.150] in IK and IS groups), with similar
      mean duration of care (median 35.0 min). Analgesia was as efficient without any
      significant difference in VAS at Tf between groups (3.1 +/- 2.3 (IK group) vs.
      3.7 +/- 2.7 (IS group), p = 0.5). Conclusions. Continuous ketamine infusion did
      not reduce morphine requirements in severe acute pain trauma patients in the out
      of-hospital emergency settings.

PMID- 24932669
TI  - Forcefield_NCAA: ab initio charge parameters to aid in the discovery and design
      of therapeutic proteins and peptides with unnatural amino acids and their
      application to complement inhibitors of the compstatin family.
AB  - We describe the development and testing of ab initio derived, AMBER ff03
      compatible charge parameters for a large library of 147 noncanonical amino acids
      including beta- and N-methylated amino acids for use in applications such as
      protein structure prediction and de novo protein design. The charge parameter
      derivation was performed using the RESP fitting approach. Studies were performed
      assessing the suitability of the derived charge parameters in discriminating the
      activity/inactivity between 63 analogs of the complement inhibitor Compstatin on
      the basis of previously published experimental IC50 data and a screening
      procedure involving short simulations and binding free energy calculations. We
      found that both the approximate binding affinity (K*) and the binding free energy
      calculated through MM-GBSA are capable of discriminating between active and
      inactive Compstatin analogs, with MM-GBSA performing significantly better. Key
      interactions between the most potent Compstatin analog that contains a
      noncanonical amino acid are presented and compared to the most potent analog
      containing only natural amino acids and native Compstatin. We make the derived
      parameters and an associated web interface that is capable of performing
      modifications on proteins using Forcefield_NCAA and outputting AMBER-ready
      topology and parameter files freely available for academic use at
      http://selene.princeton.edu/FFNCAA . The forcefield allows one to incorporate
      these customized amino acids into design applications with control over size, van
      der Waals, and electrostatic interactions. 

PMID- 24932671
TI  - Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism among Gaddi tribe
      of Indian state of Himachal Pradesh.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has
      been suggested to be positively associated with several disorders. Distribution
      of the mutant T-allele varies in ethnic and geographical populations of the
      world. AIM: The aim of the present study was to investigate the distribution of
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in a transhumant
      (Gaddi) tribal population of Himachal Pradesh dwelling at high and middle
      altitude and exposed to strong ultraviolet radiation. METHOD AND RESULTS: A total
      of 486 samples (141 males and 345 females) were randomly enrolled from the
      individuals aged 25-75 years who were unrelated up to first cousin. Among Gaddis,
      genotype frequencies of CC, CT and TT were 67.90%, 27.78% and 4.32%,
      respectively. Among males and females distribution of genotype frequencies also
      followed a similar trend. The studied population was in Hardy-Weinberg
      equilibrium (chi(2 )= 2.213, df = 1, p = 0.136). Frequency of mutant T-allele in
      the Gaddi population was found to be 0.183, which might be due to European
      ancestry, endogamous nature and selection.

PMID- 24932673
TI  - Synthesis and characterization of eight compounds of the MU8Q17 family: ScU8S17,
      CoU8S17, NiU8S17, TiU8Se17, VU8Se17, CrU8Se17, CoU8Se17, and NiU8Se17.
AB  - The solid-state MU8Q17 compounds ScU8S17, CoU8S17, NiU8S17, TiU8Se17, VU8Se17,
      CrU8Se17, CoU8Se17, and NiU8Se17 were synthesized from the reactions of the
      elements at 1173 or 1123 K. These isostructural compounds crystallize in space
      group C2h3 - C2/m of the monoclinic system in the CrU8S17 structure type. X-ray
      absorption near-edge structure spectroscopic studies of ScU8S17 indicate that it
      contains Sc3+, and hence charge balance is achieved with a composition that
      includes U3+ as well as U4+. The other compounds charge balance with M2+ and U4+.
      Magnetic susceptibility measurements on ScU8S17 indicate antiferromagnetic
      couplings and a highly reduced effective magnetic moment. Ab Initio calculations
      find the compound to be metallic. Surprisingly, the Sc-S distances are actually
      longer than all the other M-S interactions, even though the ionic radii of Sc3+,
      low-spin Cr2+, and Ni2+ are similar.

PMID- 24932672
TI  - Comparative metabolomics and structural characterizations illuminate colibactin
      pathway-dependent small molecules.
AB  - The gene cluster responsible for synthesis of the unknown molecule "colibactin"
      has been identified in mutualistic and pathogenic Escherichia coli. The pathway
      endows its producer with a long-term persistence phenotype in the human bowel, a
      probiotic activity used in the treatment of ulcerative colitis, and a
      carcinogenic activity under host inflammatory conditions. To date, functional
      small molecules from this pathway have not been reported. Here we implemented a
      comparative metabolomics and targeted structural network analyses approach to
      identify a catalog of small molecules dependent on the colibactin pathway from
      the meningitis isolate E. coli IHE3034 and the probiotic E. coli Nissle 1917. The
      structures of 10 pathway-dependent small molecules are proposed based on
      structural characterizations and network relationships. The network will provide
      a roadmap for the structural and functional elucidation of a variety of other
      small molecules encoded by the pathway. From the characterized small molecule
      set, in vitro bacterial growth inhibitory and mammalian CNS receptor antagonist
      activities are presented. 

PMID- 24932674
TI  - Life meaning is associated with suicidal ideation among depressed veterans.
AB  - Suicide is a major public health concern among U.S. veterans. Even when asked
      directly, veterans who die by suicide have been found to deny suicidal thoughts.
      Psychological assessment needs to go beyond the current risk factors and evaluate
      underlying factors that may increase suicide risk. In the present study,
      diagnostic interviews and self-report questionnaires were used to measure life
      meaning and suicidal ideation in a sample of 110 depressed veterans. Life meaning
      was significantly associated with suicidal ideation, even after accounting for
      depression and suicide history. Life meaning may be an important, previously
      ignored indicator of suicide risk. 

PMID- 24932675
TI  - Influence of noncovalent modification on dispersion state of multiwalled carbon
      nanotubes in melt-mixed immiscible polymer blends.
AB  - Multiwalled carbon nanotubes (MWNTs) were melt-mixed with polyamide6 (PA6) and
      acrylonitrile butadiene styrene copolymer (ABS) to obtain electrically conducting
      composites. MWNTs were noncovalently modified with sodium salt of 6-aminocaproic
      acid (MWNTs-m1) and 3-pyrenealdehyde (MWNTs-m2) to 'deagglomerate' MWNTs. Raman
      spectroscopic analysis indicated a G-band shift from ~1581.9 cm(-1) for pristine
      MWNTs to ~1590.2 cm(-1) for MWNTs-m1 and ~1588.8 cm(-1) for MWNTs-m2, indicating
      the interaction between MWNTs and the respective modifier molecules. Blends
      showed 'co-continuous' morphology on the addition of MWNTs. TEM observations
      showed that a higher population of pristine MWNTs exhibited a 'nanoagglomerated'
      state in PA6 and ABS phases in the case of a 40/60 PA6/ABS blend, unlike a 60/40
      blend, which depicted a higher population of 'individualized' MWNTs. Further, the
      corresponding blends with MWNTs-m1 and MWNTs-m2 showed 'nanoagglomerated' and
      'individualized' MWNTs. Blends with pristine MWNTs showed an increase in DC
      electrical conductivity with an increase in PA6 concentration in the blend.
      Moreover, the corresponding blends with MWNTs-m1 and MWNTs-m2 exhibited an
      increased DC electrical conductivity value as compared to the corresponding blend
      with pristine MWNTs. Ratio of the intensity (H1/H2) of the crystallization peak
      at lower temperature (H1) to the intensity of the crystallization peak at higher
      temperature (H2) depicted lower values for blends with pristine MWNTs as compared
      to the corresponding blends with MWNTs-m1 and MWNTs-m2. TGA studies indicated the
      formation of a thicker 'interphase' involving MWNTs and the interacting polymer
      chains. 

PMID- 24932676
TI  - The electrophoretic mobility of a weakly charged "soft" sphere in a charged
      hydrogel: application of the Lorentz reciprocal theorem.
AB  - The electrophoretic mobility of a dilute, weakly charged "soft" particle in a
      charged hydrogel modeled as an effective medium is investigated in this work.
      This is closely related to previous work (Li, F.; Allison, S. A.; Hill, R. J. J.
      Colloid Interface Sci. 2014, 423, 129-142) but approached in a different way
      using the Lorentz reciprocal theorem. Under the limiting conditions of the
      present work, it is possible to avoid numerical solution of differential
      equations. An analytical equation is derived for the mobility and applied to a
      number of cases. 

PMID- 24932677
TI  - Evaporation-induced flows inside a confined droplet of diluted saline solution.
AB  - Flow patterns inside a droplet of diluted aqueous NaCl solution confined by two
      flat substrates under natural evaporation were investigated both experimentally
      and numerically. We focused on natural convection-driven flows inside confined
      droplets at high Rayleigh numbers (i.e., the ratio of buoyancy to diffusion, Ra),
      where the convection of solutes is strongly dominant, compared to diffusion. The
      evaporated water at the free surface of the droplet builds up a concentration
      gradient inside the solution, which induces the Rayleigh convection flow. Three
      dimensional trajectories of tracer particles in the droplet were tracked, and
      axisymmetric flow motions induced by the Rayleigh convection were experimentally
      measured by using a digital in-line holographic microscopy technique. In
      addition, the effects of the confined droplet's aspect ratio and the liquid's
      molar concentration on the evaporation-induced flows were investigated. The
      convection velocity is found to be increased as molar concentration increases,
      because Rayleigh convection becomes significant at high the molar concentration
      is high (i.e. high Ra). Our numerical simulation based on the Boussinesq
      approximation fairly well predicted the velocity profiles of evaporating confined
      droplets at low concentrations. Consequently, evaporation kinetics inside the
      confined droplets can be controlled with varying droplet's aspect ratio and the
      liquid's molar concentration, which provides helpful information for the design
      of biochemical microplating with limited resources and for tuning self-assembly
      micro/nanoparticle clusters. 

PMID- 24932678
TI  - Heavy metal? Recognizing complications of metal on metal hip arthroplasty.

PMID- 24932680
TI  - Conjugation of a reactive thiol at the nucleotide binding site for site-specific
      antibody functionalization.
AB  - Described here is a UV photo-cross-linking method that utilizes the NBS
      (nucleotide binding site) for site-specific covalent functionalization of
      antibodies with reactive thiol moieties (UV-NBS(Thiol)), while preserving
      antibody activity. By synthesizing an indole-3-butyric acid (IBA) conjugated
      version of cysteine we site-specifically photo-cross-linked a reactive thiol
      moiety to antibodies at the NBS. This thiol moiety can then be used as an
      orthogonally reactive location to conjugate various types of functional ligands
      that possess a thiol reactive group through disulfide bond formation or reaction
      with a maleimide functionalized ligand. Our results demonstrate the utility of
      the UV-NBS(Thiol) method by successfully functionalizing a prostate specific
      antigen antibody (IgG(PSA)) with IBA-Thiol and subsequent reaction with maleimide
      fluorescein. An optimal UV energy of 0.5-1.5 J/cm(2) was determined to yield the
      most efficient photo-cross-linking and resulted in 1-1.5 conjugations per
      antibody while preserving antibody/antigen binding activity and Fc recognition.
      Utilizing the IBA-Thiol ligand allows for an efficient means of site-specifically
      conjugating UV sensitive functionalities to antibody NBS that would otherwise not
      have been amenable by the previously described UV-NBS photo-cross-linking method.
      The UV-NBS(Thiol) conjugation strategy can be utilized in various diagnostic and
      therapeutic applications with nearly limitless potential for the preparation of
      site-specific covalent conjugation of affinity tags, fluorescent molecules,
      peptides, and chemotherapeutics to antibodies. 

PMID- 24932679
TI  - School social fragmentation, economic deprivation and social cohesion and
      adolescent physical inactivity: a longitudinal study.
AB  - OBJECTIVES: To examine the independent influence of school economic deprivation,
      social fragmentation, and social cohesion on the likelihood of participating in
      no physical activity among students. METHODS: Data are from a large-scale
      longitudinal study of schools based in disadvantaged communities in Quebec,
      Canada. Questionnaires were administered every year between 2002 and 2008 among n
      = 14,924 students aged 12 to 18 from a sample of 70 schools. Cross-sectional and
      longitudinal analyses were conducted. Multilevel modeling was utilized to account
      for the clustering of students within schools. Schools were categorized as being
      low, moderate or high economic deprivation, social fragmentation and social
      cohesion. Those who indicated that they do no participate in any physical
      activity during the week were identified as being physically inactive. RESULTS:
      In baseline multilevel cross-sectional analyses, adolescents attending schools in
      the highest (compared to the lowest) levels of socioeconomic deprivation and
      social fragmentation were more likely to be physically inactive (OR = 1.33, 95%
      CI = 1.03, 1.72; and OR = 1.24, 95% CI = 0.98, 1.56, respectively). Conversely,
      students attending schools with the highest cohesion were less likely to be
      physically inactive (OR = 0.78, 95% CI = 0.61, 0.99). In longitudinal analysis,
      physically active students who attended schools with the highest social
      fragmentation were more likely to become physically inactive over two years (OR =
      1.65, 95% CI = 1.09, 2.51). CONCLUSION: The school socioeconomic environment
      appears to be an important contextual influence on participation in no physical
      activity among adolescents. Following adolescents beyond two years is necessary
      to determine if these environments have a lasting effect on physical activity
      behavior.

PMID- 24932681
TI  - Long term effect of curcumin in regulation of glycolytic pathway and angiogenesis
      via modulation of stress activated genes in prevention of cancer.
AB  - Oxidative stress, an important factor in modulation of glycolytic pathway and
      induction of stress activated genes, is further augmented due to reduced
      antioxidant defense system, which promotes cancer progression via inducing
      angiogenesis. Curcumin, a naturally occurring chemopreventive phytochemical, is
      reported to inhibit carcinogenesis in various experimental animal models.
      However, the underlying mechanism involved in anticarcinogenic action of curcumin
      due to its long term effect is still to be reported because of its rapid
      metabolism, although metabolites are accumulated in tissues and remain for a
      longer time. Therefore, the long term effect of curcumin needs thorough
      investigation. The present study aimed to analyze the anticarcinogenic action of
      curcumin in liver, even after withdrawal of treatment in Dalton's lymphoma
      bearing mice. Oxidative stress observed during lymphoma progression reduced
      antioxidant enzyme activities, and induced angiogenesis as well as activation of
      early stress activated genes and glycolytic pathway. Curcumin treatment resulted
      in activation of antioxidant enzyme super oxide dismutase and down regulation of
      ROS level as well as activity of ROS producing enzyme NADPH:oxidase, expression
      of stress activated genes HIF-1alpha, cMyc and LDH activity towards normal level.
      Further, it lead to significant inhibition of angiogenesis, observed via MMPs
      activity, PKCalpha and VEGF level, as well as by matrigel plug assay. Thus
      findings of this study conclude that the long term effect of curcumin shows
      anticarcinogenic potential via induction of antioxidant defense system and
      inhibition of angiogenesis via down regulation of stress activated genes and
      glycolytic pathway in liver of lymphoma bearing mice. 

PMID- 24932682
TI  - Human 45,X fibroblast transcriptome reveals distinct differentially expressed
      genes including long noncoding RNAs potentially associated with the
      pathophysiology of Turner syndrome.
AB  - Turner syndrome is a chromosomal abnormality characterized by the absence of
      whole or part of the X chromosome in females. This X aneuploidy condition is
      associated with a diverse set of clinical phenotypes such as gonadal dysfunction,
      short stature, osteoporosis and Type II diabetes mellitus, among others. These
      phenotypes differ in their severity and penetrance among the affected
      individuals. Haploinsufficiency for a few X linked genes has been associated with
      some of these disease phenotypes. RNA sequencing can provide valuable insights to
      understand molecular mechanism of disease process. In the current study, we have
      analysed the transcriptome profiles of human untransformed 45,X and 46,XX
      fibroblast cells and identified differential expression of genes in these two
      karyotypes. Functional analysis revealed that these differentially expressing
      genes are associated with bone differentiation, glucose metabolism and gonadal
      development pathways. We also report differential expression of lincRNAs in X
      monosomic cells. Our observations provide a basis for evaluation of cellular and
      molecular mechanism(s) in the establishment of Turner syndrome phenotypes. 

PMID- 24932683
TI  - Genome-wide identification and characterization of long intergenic non-coding
      RNAs in Ganoderma lucidum.
AB  - Ganoderma lucidum is a white-rot fungus best-known for its medicinal activities.
      We have previously sequenced its genome and annotated the protein coding genes.
      However, long non-coding RNAs in G. lucidum genome have not been analyzed. In
      this study, we have identified and characterized long intergenic non-coding RNAs
      (lincRNA) in G. lucidum systematically. We developed a computational pipeline,
      which was used to analyze RNA-Seq data derived from G. lucidum samples collected
      from three developmental stages. A total of 402 lincRNA candidates were
      identified, with an average length of 609 bp. Analysis of their adjacent protein
      coding genes (apcGenes) revealed that 46 apcGenes belong to the pathways of
      triterpenoid biosynthesis and lignin degradation, or families of cytochrome P450,
      mating type B genes, and carbohydrate-active enzymes. To determine if lincRNAs
      and these apcGenes have any interactions, the corresponding pairs of lincRNAs and
      apcGenes were analyzed in detail. We developed a modified 3' RACE method to
      analyze the transcriptional direction of a transcript. Among the 46 lincRNAs, 37
      were found unidirectionally transcribed, and 9 were found bidirectionally
      transcribed. The expression profiles of 16 of these 37 lincRNAs were found to be
      highly correlated with those of the apcGenes across the three developmental
      stages. Among them, 11 are positively correlated (r>0.8) and 5 are negatively
      correlated (r<-0.8). The co-localization and co-expression of lincRNAs and those
      apcGenes playing important functions is consistent with the notion that lincRNAs
      might be important regulators for cellular processes. In summary, this represents
      the very first study to identify and characterize lincRNAs in the genomes of
      basidiomycetes. The results obtained here have laid the foundation for study of
      potential lincRNA-mediated expression regulation of genes in G. lucidum. 

PMID- 24932684
TI  - MIF family members cooperatively inhibit p53 expression and activity.
AB  - The tumor suppressor p53 is induced by genotoxic stress in both normal and
      transformed cells and serves to transcriptionally coordinate cell cycle
      checkpoint control and programmed cell death responses. Macrophage migration
      inhibitory factor (MIF) is an autocrine and paracrine acting cytokine/growth
      factor that promotes lung adenocarcinoma cell motility, anchorage-independence
      and neo-angiogenic potential. Several recent studies indicate that the only known
      homolog of MIF, D-dopachrome tautomerase (D-DT - also referred to as MIF-2), has
      functionally redundant activities with MIF and cooperatively promotes MIF
      dependent pro-tumorigenic phenotypes. We now report that MIF and D-DT
      synergistically inhibit steady state p53 phosphorylation, stabilization and
      transcriptional activity in human lung adenocarcinoma cell lines. The combined
      loss of MIF and D-DT by siRNA leads to dramatically reduced cell cycle
      progression, anchorage independence, focus formation and increased programmed
      cell death when compared to individual loss of MIF or D-DT. Importantly, p53
      mutant and p53 null lung adenocarcinoma cell lines were only nominally rescued
      from the cell growth effects of MIF/D-DT combined deficiency suggesting only a
      minor role for p53 in these transformed cell growth phenotypes. Finally,
      increased p53 activation was found to be independent of aberrantly activated AMP
      activated protein kinase (AMPK) that occurs in response to MIF/D-DT-deficiency
      but is dependent on reactive oxygen species (ROS) that mediate aberrant AMPK
      activation in these cells. Combined, these findings suggest that both p53
      wildtype and mutant human lung adenocarcinoma tumors rely on MIF family members
      for maximal cell growth and survival. 

PMID- 24932685
TI  - Insulin-like growth factor 2 silencing restores taxol sensitivity in drug
      resistant ovarian cancer.
AB  - Drug resistance is an obstacle to the effective treatment of ovarian cancer. We
      and others have shown that the insulin-like growth factor (IGF) signaling pathway
      is a novel potential target to overcome drug resistance. The purpose of this
      study was to validate IGF2 as a potential therapeutic target in drug resistant
      ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An
      analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer
      cohort showed that high IGF2 mRNA expression is significantly associated with
      shortened interval to disease progression and death, clinical indicators of drug
      resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2
      mRNA levels measured in cell lines resistant to various microtubule-stabilizing
      agents including Taxol were found to be significantly elevated compared to the
      drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was
      investigated in vitro and in vivo. Transient IGF2 knockdown significantly
      sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian
      cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug
      resistance, wherein the maximal tolerated dose of Taxol did not delay tumor
      growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits
      signals from IGF1 and IGF2) using a monoclonal antibody did not alter the
      response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY
      T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a
      potential therapeutic target in drug resistant ovarian cancer and show that
      directly targeting IGF2 may be a preferable strategy compared with targeting
      IGF1R alone. 

PMID- 24932686
TI  - Helicobacter hepaticus induces an inflammatory response in primary human
      hepatocytes.
AB  - Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma
      in certain strains of mice. Until now the pathogenic role of Helicobacter species
      on human liver tissue is still not clarified though Helicobacter species
      identification in human liver cancer was successful in case controlled studies.
      Therefore we established an in vitro model to investigate the interaction of
      primary human hepatocytes (PHH) with Helicobacter hepaticus. Successful co
      culturing of PHH with Helicobacter hepaticus was confirmed by visualization of
      motile bacteria by two-photon-microscopy. Isolated human monocytes were
      stimulated with PHH conditioned media. Changes in mRNA expression of acute phase
      cytokines and proteins in PHH and stimulated monocytes were determined by Real
      time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture
      supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA
      expression of Interleukin-1 beta (IL-1beta), Tumor necrosis factor-alpha,
      Interleukin-8 (IL-8) and Monocyte chemotactic protein-1 (MCP-1) in PHH (p<0.05)
      resulting in a corresponding increase of IL-8 and MCP-1 concentrations in PHH
      supernatants (p<0.05). IL-8 and IL-1beta mRNA expression was induced in monocytes
      stimulated with Helicobacter hepaticus infected PHH conditioned media (p<0.05).
      An increase of Cyclooxygenase-2 mRNA expression was observed, with a concomitant
      increase of prostaglandin E2 concentration in PHH supernatants at 24 and 48 h
      (p<0.05). In contrast, at day 7 of co-culture, no persistent elevation of
      cytokine mRNA could be detected. High expression of intercellular adhesion
      molecule-1 on PHH cell membranes after co-culture was shown by two-photon
      microscopy and confirmed by flow-cytometry. Finally, expression of Cytochrome
      P450 3A4 and albumin mRNA were downregulated, indicating an impairment of
      hepatocyte synthesis function by Helicobacter hepaticus presence. This is the
      first in vitro model demonstrating a pathogenic effect of a Helicobacter spp. on
      human liver cells, resulting in an inflammatory response with increased synthesis
      of inflammatory mediators and consecutive monocyte activation.

PMID- 24932688
TI  - Clearance of Aspergillus fumigatus is impaired in the airway in allergic
      inflammation.
AB  - BACKGROUND: Aspergillus fumigatus (Af) sometimes colonizes and persists within
      the respiratory tree in some patients with asthma. To date, the precise reasons
      why the clearance of Af is impaired in patients with asthma remain unknown.
      OBJECTIVE: To characterize the effects of allergic airway inflammation on
      clearance of Af. METHODS: Control and Dermatophagoides farinae (Df) allergen
      sensitized BALB/c mice were intranasally infected with Af. After 2 and 9 days of
      infection, the pathology, fungal burden, and cytokine profile in lung tissue were
      compared. In a different set of experiments, the phagocytotic activity of
      alveolar macrophages and the expression of their pathogen recognition receptors
      also were determined. RESULTS: The Af conidia and neutrophilic airway
      inflammation disappeared by day 9 after infection in control mice. In Df
      sensitized mice, Af conidia and neutrophilic and eosinophilic airway inflammation
      persisted at day 9 after infection. Compared with control mice, Df allergen
      sensitized mice showed significant increases in interleukin (IL)-5 and decreases
      in IL-12 and interferon-gamma in lung tissues at day 2 after infection. Most
      importantly, compared with Af-infected non-Df-sensitized mice, IL-17 in lung
      tissues was significantly decreased in Df allergen-sensitized Af-infected mice at
      day 2 after infection but was significantly increased at day 9. Alveolar
      macrophages isolated from Df allergen-sensitized mice exhibited significant
      decreases in phagocytotic activity and expression of Toll-like receptor-4 and
      dectin-1 compared with those from control mice. CONCLUSION: In the airway of
      patients with allergy, T-helper cell type 2-dominant immunity potentially affects
      the expression of pathogen recognition receptors and attenuates cellular defense
      against Af. Prolonged IL-17 production also could play an important role.

PMID- 24932689
TI  - Chemokine expression in diverse nonimmediate drug hypersensitivity reactions:
      focus on thymus activation-regulated chemokine, cutaneous T-cell-attracting
      chemokine, and interleukin-10.
AB  - BACKGROUND: Skin infiltration of different types of T lymphocytes is responsible
      for inflammatory profiles of nonimmediate drug hypersensitivity reactions
      (niDHRs). Important chemokines attracting skin-specific homing T cells include
      thymus activation-regulated chemokine (TARC) and cutaneous T-cell-attracting
      chemokine (CTACK). Interleukin-10 (IL-10) is a potent chemokine attracting CD8(+)
      T cells. OBJECTIVE: To investigate serum levels of TARC, CTACK, and IL-10 in
      patients with niDHRs and evaluate the correlation among these 3 chemokines.
      METHODS: Forty patients, including 19 patients with Stevens-Johnson syndrome and
      toxic epidermal necrolysis and 21 patients with maculopapular exanthema, and 21
      healthy donors were recruited into the study. Clinical data of patients were
      obtained. Serum TARC, CTACK, and IL-10 levels were determined by enzyme-linked
      immunosorbent assay. RESULTS: Serum levels of TARC, CTACK, and IL-10 were
      significantly elevated in patients with niDHRs compared with those in normal
      controls (P < .05, P < .001, P < .001, respectively). The CTACK and IL-10 levels
      were significantly higher (P < .05, P < .001) in patients with Stevens-Johnson
      syndrome and toxic epidermal necrolysis than in normal controls. Patients with
      maculopapular exanthema exhibited higher levels of TARC, CTACK, and IL-10
      compared with normal controls (P < .001, P < .001, P < .05). Serum CTACK levels
      were positively correlated with TARC levels in all 40 patients (rs = 0.3422, P <
      .05). Serum CTACK levels positively correlated with detachment of body surface
      area in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (rs
      = 0.510, P < .05). CONCLUSION: These results support a role for TARC, CTACK, and
      IL-10 in the pathogenesis of niDHRs for their chemotactic ability to attract
      different T-cell subtypes and different functional severities in niDHRs.

PMID- 24932690
TI  - Extracellular polysaccharide production by a novel osmotolerant marine strain of
      Alteromonas macleodii and its application towards biomineralization of silver.
AB  - The present study demonstrates exopolysaccharide production by an osmotolerant
      marine isolate and also describes further application of the purified
      polysaccharide for production of colloidal suspension of silver nanoparticles
      with narrow size distribution. Phylogenetic analysis based on 16S r RNA gene
      sequencing revealed close affinity of the isolate to Alteromonas macleodii.
      Unlike earlier reports, where glucose was used as the carbon source, lactose was
      found to be the most suitable substrate for polysaccharide production. The strain
      was capable of producing 23.4 gl(-1) exopolysaccharide with a productivity of 7.8
      gl(-1) day(-1) when 15% (w/v) lactose was used as carbon source. Furthermore, the
      purified polysaccharide was able to produce spherical shaped silver nanoparticles
      of around 70 nm size as characterized by Uv-vis spectroscopy, Dynamic light
      scattering and Transmission electron microscopy. These observations suggested
      possible commercial potential of the isolated strain for production of a
      polysaccharide which has the capability of synthesizing biocompatible metal
      nanoparticle.

PMID- 24932691
TI  - Febuxostat in adenosine phosphoribosyltransferase deficiency.

PMID- 24932694
TI  - Introduction to the World Society for Reconstructive Microsurgery 2013 meeting.

PMID- 24932692
TI  - Regulation of HIV-Gag expression and targeting to the endolysosomal/secretory
      pathway by the luminal domain of lysosomal-associated membrane protein (LAMP-1)
      enhance Gag-specific immune response.
AB  - We have previously demonstrated that a DNA vaccine encoding HIV-p55gag in
      association with the lysosomal associated membrane protein-1 (LAMP-1) elicited a
      greater Gag-specific immune response, in comparison to a DNA encoding the native
      gag. In vitro studies have also demonstrated that LAMP/Gag was highly expressed
      and was present in MHCII containing compartments in transfected cells. In this
      study, the mechanisms involved in these processes and the relative contributions
      of the increased expression and altered traffic for the enhanced immune response
      were addressed. Cells transfected with plasmid DNA constructs containing p55gag
      attached to truncated sequences of LAMP-1 showed that the increased expression of
      gag mRNA required p55gag in frame with at least 741 bp of the LAMP-1 luminal
      domain. LAMP luminal domain also showed to be essential for Gag traffic through
      lysosomes and, in this case, the whole sequence was required. Further analysis of
      the trafficking pathway of the intact LAMP/Gag chimera demonstrated that it was
      secreted, at least in part, associated with exosome-like vesicles. Immunization
      of mice with LAMP/gag chimeric plasmids demonstrated that high expression level
      alone can induce a substantial transient antibody response, but targeting of the
      antigen to the endolysosomal/secretory pathways was required for establishment of
      cellular and memory response. The intact LAMP/gag construct induced
      polyfunctional CD4+ T cell response, which presence at the time of immunization
      was required for CD8+ T cell priming. LAMP-mediated targeting to
      endolysosomal/secretory pathway is an important new mechanistic element in LAMP
      mediated enhanced immunity with applications to the development of novel anti-HIV
      vaccines and to general vaccinology field. 

PMID- 24932695
TI  - Introduction to the World Society for Reconstructive Microsurgery 2013 scientific
      meeting and paper issue.

PMID- 24932693
TI  - Transformation products and human metabolites of triclocarban and triclosan in
      sewage sludge across the United States.
AB  - Removal of triclocarban (TCC) and triclosan (TCS) from wastewater is a function
      of adsorption, abiotic degradation, and microbial mineralization or
      transformation, reactions that are not currently controlled or optimized in the
      pollution control infrastructure of standard wastewater treatment. Here, we
      report on the levels of eight transformation products, human metabolites, and
      manufacturing byproducts of TCC and TCS in raw and treated sewage sludge. Two
      sample sets were studied: samples collected once from 14 wastewater treatment
      plants (WWTPs) representing nine states, and multiple samples collected from one
      WWTP monitored for 12 months. Time-course analysis of significant mass fluxes
      (alpha=0.01) indicate that transformation of TCC (dechlorination) and TCS
      (methylation) occurred during sewage conveyance and treatment. Strong linear
      correlations were found between TCC and the human metabolite 2'-hydroxy-TCC
      (r=0.84), and between the TCC-dechlorination products dichlorocarbanilide (DCC)
      and monochlorocarbanilide (r=0.99). Mass ratios of DCC-to-TCC and of methyl
      triclosan (MeTCS)-to-TCS, serving as indicators of transformation activity,
      revealed that transformation was widespread under different treatment regimes
      across the WWTPs sampled, though the degree of transformation varied
      significantly among study sites (alpha=0.01). The analysis of sludge sampled
      before and after different unit operation steps (i.e., anaerobic digestion,
      sludge heat treatment, and sludge drying) yielded insights into the extent and
      location of TCC and TCS transformation. Results showed anaerobic digestion to be
      important for MeTCS transformation (37-74%), whereas its contribution to partial
      TCC dechlorination was limited (0.4-2.1%). This longitudinal and nationwide
      survey is the first to report the occurrence of transformation products, human
      metabolites, and manufacturing byproducts of TCC and TCS in sewage sludge.

PMID- 24932696
TI  - Neuroprotection against Abeta25-35-induced apoptosis by Salvia miltiorrhiza
      extract in SH-SY5Y cells.
AB  - The neurotoxicity of beta-amyloid protein (Abeta) contributes significantly to
      the pathogenesis of Alzheimer's disease (AD), and hence the attractive
      therapeutic strategies focusing on the modulation of Abeta-induced neurotoxicity
      are warranted. The present study aims to investigate the neuroprotection and
      underlying mechanisms by which Salvia miltiorrhiza Bunge (Lamiaceae) extract
      (SME) protects against Abeta25-35-induced apoptosis in SH-SY5Y cells. 2h Pre
      treatment of SH-SY5Y cells with SME (0.01, 0.1 or 0.2mg raw herb/ml)
      concentration-dependently attenuated Abeta25-35-induced cell death, as evidenced
      by the increase in cell viability and decrease in neuronal apoptosis. In
      addition, SME suppressed the increased intracellular reactive oxygen species
      levels, decreased the protein expression of cleaved caspase-3, cytosolic
      cytochrome c, and Bax/Bcl-2 ratio. These findings taken together suggest that SME
      provides substantial neuroprotection against Abeta25-35-induced neurotoxicity in
      SH-SY5Y cells, at least in part, via inhibiting oxidative stress and attenuating
      the mitochondria-dependent apoptotic pathway. The approach used in this study may
      also be useful for the screening of therapeutic agents for AD and other related
      neurodegenerative disease. 

PMID- 24932697
TI  - Gastrodin protects against MPP(+)-induced oxidative stress by up regulates heme
      oxygenase-1 expression through p38 MAPK/Nrf2 pathway in human dopaminergic cells.
AB  - Although the etiology of PD remains unclear, increasing evidence has shown that
      oxidative stress plays an important role in its pathogenesis and that of other
      neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent
      of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to
      display antioxidant activity. The present study aimed to investigate the
      protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP(+))-induced
      oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying
      mechanism for this neuroprotection. Results indicate that pre-treatment with
      gastrodin for 1h significantly reduced the MPP(+)-induced viability loss,
      apoptotic rate and attenuated MPP(+)-mediated ROS production. In addition,
      gastrodin inhibited MPP(+)-induced lowered membrane potential, decreased Bcl
      2/Bax ratio. Moreover, we have revealed the gastrodin increased Nrf2 nuclear
      translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for
      the first time revealed gastrodin could increased antioxidant enzyme HO-1
      expression in concentration-dependent and time-dependent manners. HO-1 siRNA
      transfection was employed, and confirmed gastrodin could active the expression of
      HO-1. And the increase in HO-1 expression was correlated with the protective
      effect of gastrodin against MPP(+)-induced injury. Because the inhibitor of HO-1
      activity, ZnPP reversed the protective effect of gastrodin against MPP(+)-induced
      cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580,
      concentration-dependently blocked on gastrodin-induced HO-1 expression, and
      meanwhile SB203580 reversed the protective effect of gastrodin against MPP(+)
      induced cell death. Taken together, these findings suggest that gastrodin can
      induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway,
      thereby protecting the SH-SY5Y cells from MPP(+)-induced oxidative cell death.
      Thus our study indicates that gastrodin has a partial cytoprotective role in
      dopaminergic cell culture systems and could be of importance for the treatment of
      PD and other oxidative stress-related diseases. 

PMID- 24932698
TI  - WITHDRAWN: Long-term ventilation in children: Ten years later.
AB  - This article has been withdrawn for editorial reasons because the journal will be
      published only in English. In order to avoid duplicated records, this article can
      be found at http://dx.doi.org/10.1016/j.rppnen.2014.03.017. 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- 24932699
TI  - Detection of mercury(II) ions using colorimetric gold nanoparticles on paper
      based analytical devices.
AB  - An on-field colorimetric sensing strategy employing gold nanoparticles (AuNPs)
      and a paper-based analytical platform was investigated for mercury ion (Hg(2+))
      detection at water sources. By utilizing thymine-Hg(2+)-thymine (T-Hg(2+)-T)
      coordination chemistry, label-free detection oligonucleotide sequences were
      attached to unmodified gold nanoparticles to provide rapid mercury ion sensing
      without complicated and time-consuming thiolated or other costly labeled probe
      preparation processes. Not only is this strategy's sensing mechanism specific
      toward Hg(2+), rather than other metal ions, but also the conformational change
      in the detection oligonucleotide sequences introduces different degrees of AuNP
      aggregation that causes the color of AuNPs to exhibit a mixture variance. To
      eliminate the use of sophisticated equipment and minimize the power requirement
      for data analysis and transmission, the color variance of multiple detection
      results were transferred and concentrated on cellulose-based paper analytical
      devices, and the data were subsequently transmitted for the readout and storage
      of results using cloud computing via a smartphone. As a result, a detection limit
      of 50 nM for Hg(2+) spiked pond and river water could be achieved. Furthermore,
      multiple tests could be performed simultaneously with a 40 min turnaround time.
      These results suggest that the proposed platform possesses the capability for
      sensitive and high-throughput on-site mercury pollution monitoring in resource
      constrained settings. 

PMID- 24932700
TI  - Stiff filamentous virus translocations through solid-state nanopores.
AB  - The ionic conductance through a nanometer-sized pore in a membrane changes when a
      biopolymer slides through it, making nanopores sensitive to single molecules in
      solution. Their possible use for sequencing has motivated numerous studies on how
      DNA, a semi-flexible polymer, translocates nanopores. Here we study voltage
      driven dynamics of the stiff filamentous virus fd with experiments and
      simulations to investigate the basic physics of polymer translocations. We find
      that the electric field distribution aligns an approaching fd with the nanopore,
      promoting its capture, but it also pulls fd sideways against the membrane after
      failed translocation attempts until thermal fluctuations reorient the virus for
      translocation. fd is too stiff to translocate in folded configurations. It
      therefore translocates linearly, exhibiting a voltage-independent mobility and
      obeying first-passage-time statistics. Surprisingly, lengthwise Brownian motion
      only partially accounts for the translocation velocity fluctuations. We also
      observe a voltage-dependent contribution whose origin is only partially
      determined. 

PMID- 24932701
TI  - GATA4 is essential for bone mineralization via ERalpha and TGFbeta/BMP pathways.
AB  - Osteoporosis is a disease characterized by low bone mass, leading to an increased
      risk of fragility fractures. GATA4 is a zinc-finger transcription factor that is
      important in several tissues, such as the heart and intestines, and has recently
      been shown to be a pioneer factor for estrogen receptor alpha (ERalpha) in
      osteoblast-like cells. Herein, we demonstrate that GATA4 is necessary for
      estrogen-mediated transcription and estrogen-independent mineralization in vitro.
      In vivo deletion of GATA4, driven by Cre-recombinase in osteoblasts, results in
      perinatal lethality, decreased trabecular bone properties, and abnormal bone
      development. Microarray analysis revealed GATA4 suppression of TGFbeta signaling,
      necessary for osteoblast progenitor maintenance, and concomitant activation of
      BMP signaling, necessary for mineralization. Indeed, pSMAD1/5/8 signaling,
      downstream of BMP signaling, is decreased in the trabecular region of conditional
      knockout femurs, and pSMAD2/3, downstream of TGFbeta signaling, is increased in
      the same region. Together, these experiments demonstrate the necessity of GATA4
      in osteoblasts. Understanding the role of GATA4 to regulate the tissue
      specificity of estrogen-mediated osteoblast gene regulation and estrogen
      independent bone differentiation may help to develop therapies for postmenopausal
      osteoporosis.

PMID- 24932702
TI  - Association between temperature and emergency room visits for cardiorespiratory
      diseases, metabolic syndrome-related diseases, and accidents in metropolitan
      Taipei.
AB  - OBJECTIVE: This study evaluated risks of the emergency room visits (ERV) for
      cerebrovascular diseases, heart diseases, ischemic heart disease, hypertensive
      diseases, chronic renal failure (CRF), diabetes mellitus (DM), asthma, chronic
      airway obstruction not elsewhere classified (CAO), and accidents associated with
      the ambient temperature from 2000 to 2009 in metropolitan Taipei. METHODS: The
      distributed lag non-linear model was used to estimate the cumulative relative
      risk (RR) and confidence interval (CI) of cause-specific ERV associated with
      daily temperature from lag 0 to lag 3 after controlling for potential
      confounders. RESULTS: This study identified that temperatures related to the
      lowest risk of ERV was 26  degrees C for cerebrovascular diseases, 18  degrees C
      for CRF, DM, and accidents, and 30  degrees C for hypertensive diseases, asthma,
      and CAO. These temperatures were used as the reference temperatures to measure RR
      for the corresponding diseases. A low temperature (14 degrees C) increased the
      ERV risk for cerebrovascular diseases, hypertensive diseases, and asthma, with
      respective cumulative 4-day RRs of 1.56 (95% CI: 1.23, 1.97), 1.78 (95% CI: 1.37,
      2.34), and 2.93 (95% CI: 1.26, 6.79). The effects were greater on, or after, lag
      one. At 32 degrees C, the cumulative 4-day RR for ERV was significant for CRF (RR
      = 2.36; 95% CI: 1.33, 4.19) and accidents (RR = 1.23; 95% CI: 1.14, 1.33) and the
      highest RR was seen on lag 0 for CRF (RR = 1.69; 95% CI: 1.01, 3.58), DM (RR =
      1.69; 95% CI: 1.09, 2.61), and accidents (RR = 1.19; 95% CI: 1.11, 1.27).
      CONCLUSIONS: Higher temperatures are associated with the increased ERV risks for
      CRF, DM, and accidents and lower temperatures with the increased ERV risks for
      cerebrovascular diseases, hypertensive diseases, and asthma in the subtropical
      metropolitan.

PMID- 24932703
TI  - Subcutaneous and intravenous ceftriaxone administration in patients more than 75
      years of age.
AB  - OBJECTIVE: We wanted to compare the first line intravenous administration of
      ceftriaxone to a subcutaneous administration in patients more than 75 years of
      age. METHOD: We performed a retrospective monocentric study on all patients more
      than 75 years of age admitted to the Ales hospital between January 1 and December
      31, 2011, having received at least two doses of ceftriaxone intravenously (IV) or
      subcutaneously (SC). RESULTS: One hundred and forty-eight patients (70 females/78
      males patients) were included, 110 received ceftriaxone IV and 38 SC. They were a
      mean age of 84.7 years, older in the SC group (86.9 years) than in the IV group
      (83.9 years) (P = 0.0052). The SC group patients presented more frequently with
      dementia (57% vs. 25% P = 0.001), were more often bedridden (22% vs. 7% P =
      0.023), had a higher mean World Health Organization status (3.13 vs. 2.76, P =
      0.0181), and higher ADL score (7.79 vs. 5.76, P = 0.0056). There was no
      statistical difference for isolated bacteria, site of infection, death rate, and
      patients cured. CONCLUSION: Subcutaneous ceftriaxone administration seems to be
      preferred for fragile elderly patients independently of disease severity. This
      administration is not associated to an impaired effectiveness or to an increased
      death rate.

PMID- 24932705
TI  - Electrocution-related mortality: a review of 71 deaths by low-voltage electrical
      current in Guangdong, China, 2001-2010.
AB  - The aim of this study was to investigate the epidemiological characteristics of
      low-voltage electrocution deaths in Guangdong, China. Three thousand three
      hundred seventy autopsy reports from the Department of Forensic Pathology,
      Zhongshan School of Medicine, Sun Yat-Sen University, over a period of 10 years
      (2001-2010) were reviewed, of which 71 low-voltage electrocution cases were
      identified. The descriptive statistical analyses were carried out with the
      application of SPSS 19.0 software. Electrocution accounted for 2.11% of all
      autopsied cases. The age range was 3 to 57 years with a mean age of 31.77 +/-
      11.0 years. The average age of male victims was 33.08 +/- 10.77 years, and that
      of female victims was 22.63 +/- 11.06 years. The majority of the victims (87.33%)
      were male. Among the circumstances leading to electrocution, most of them
      occurred in factory and in the street. Considering the contact details, deaths
      were caused most frequently by touching electrical wires (n = 27, 38.02%),
      followed by touching charged machine (n = 20, 28.17%). There were no suicide and
      homicide cases. Of all electrocution cases, 50.70% occurred during the summer
      period from June through August. The upper extremity was the most frequently
      involved contact site (59.72%). No electrical burn marks were present in 14 cases
      (19.72%). Our results indicated that most deaths from electrocution occur more
      often in factories, in summer seasons, and to young male workers, which can help
      in the development of a differentiated strategy for the prevention of
      electrocution, while taking into consideration sex, age, occupation, and season
      of the year. 

PMID- 24932704
TI  - Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT
      molecular subgroups reveal different therapeutic responses to adjuvant
      chemotherapy.
AB  - Medulloblastoma (MB) is one of the most common primary central nervous system
      tumors in children. Data is lacking of a large cohort of medulloblastoma patients
      in China. Also, our knowledge on the sensitivity of different molecular subgroups
      of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited.
      The authors performed a retrospective study of 173 medulloblastoma patients
      treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded
      (FFPE) tissues were available in all the cases and sections were stained to
      classify histological and molecular subgroups. Univariate and multivariate
      analyses were used to investigate prognostic factors. Of 173 patients, there were
      118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall
      survival (OS) rates for all patients, children and adults were 52%, 48% and 63%,
      respectively. After multivariate analysis, postoperative primary radiation
      therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors
      influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found
      significantly improving the survival of children (p<0.001) while it was not a
      significant prognostic factor for adult patients. Moreover, patients in WNT
      subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes)
      given postoperative adjuvant therapies. Postoperative primary RT was found to be
      a strong prognostic factor influencing the survival in all histological and
      molecular subgroups (p<0.001). Postoperative primary CHT was found significantly
      to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS
      p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p =
      0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p
      = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055).
      Our study showed postoperative primary CHT significantly influence the survival
      of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of
      MB. 

PMID- 24932706
TI  - Molecular approaches for detection of the multi-drug resistant tuberculosis (MDR
      TB) in Bangladesh.
AB  - The principal obstacles in the treatment of tuberculosis (TB) are delayed and
      inaccurate diagnosis which often leads to the onset of the drug resistant TB
      cases. To avail the appropriate treatment of the patients and to hinder the
      transmission of drug-resistant TB, accurate and rapid detection of resistant
      isolates is critical. Present study was designed to demonstrate the efficacy of
      molecular techniques inclusive of line probe assay (LPA) and GeneXpert MTB/RIF
      methods for the detection of multi-drug resistant (MDR) TB. Sputum samples from
      300 different categories of treated and new TB cases were tested for the
      detection of possible mutation in the resistance specific genes (rpoB, inhA and
      katG) through Genotype MTBDRplus assay or LPA and GeneXpert MTB/RIF tests.
      Culture based conventional drug susceptibility test (DST) was also carried out to
      measure the efficacy of the molecular methods employed. Among 300 samples, 191
      (63.7%) and 193 (64.3%) cases were found to be resistant against rifampicin in
      LPA and GeneXpert methods, respectively; while 189 (63%) cases of rifampicin
      resistance were detected by conventional DST methods. On the other hand, 196
      (65.3%) and 191 (63.7%) isolates showed isoniazid resistance as detected by LPA
      and conventional drug susceptibility test (DST), respectively. Among the drug
      resistant isolates (collectively 198 in LPA and 193 in conventional DST), 189
      (95.6%) and 187 (96.9%) were considered to be MDR as examined by LPA and
      conventional DST, respectively. Category-II and -IV patients encountered higher
      frequency of drug resistance compared to those from category-I and new cases.
      Considering the higher sensitivity, specificity and accuracy along with the
      required time to results significantly shorter, our study supports the adoption
      of LPA and GeneXpert assay as efficient tools in detecting drug resistant TB in
      Bangladesh. 

PMID- 24932707
TI  - Management of atypical cranial meningiomas, part 1: predictors of recurrence and
      the role of adjuvant radiation after gross total resection.
AB  - BACKGROUND: Indications for external beam radiation therapy (EBRT) for atypical
      meningiomas (AMs) remain unclear. OBJECTIVE: To analyze features associated with
      recurrence in AM patients after gross total resection (GTR) and to assess the
      relative benefit of EBRT in a retrospective cohort study. METHODS: One hundred
      fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0
      months) were examined for possible predictors of recurrence (age, sex, location,
      volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum
      tests were used to analyze the association between these predictors and use of
      EBRT. The impact on recurrence for these predictors and EBRT was analyzed with
      Kaplan-Meier and Cox regression. RESULTS: Of 151 patients, 13 (8.6%) experienced
      recurrence after GTR (median, 47.0 months). Multivariate analysis identified
      elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of
      recurrence. Larger volume (P = .96) was not associated with recurrence but was
      more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR
      (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months).
      The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/EBRT
      were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated
      no difference in progression-free survival or overall survival after GTR vs
      GTR/EBRT (P = .8, P > .99). CONCLUSION: Brain invasion and high mitotic rates may
      predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free
      survival and overall survival, suggesting that observation rather than EBRT may
      be indicated after GTR.

PMID- 24932708
TI  - Management of atypical cranial meningiomas, part 2: predictors of progression and
      the role of adjuvant radiation after subtotal resection.
AB  - BACKGROUND: The efficacies of adjuvant stereotactic radiosurgery (SRS) and
      external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after
      subtotal resection (STR) remain unclear. OBJECTIVE: To analyze the clinical,
      histopathological, and radiographic features associated with progression in AM
      patients after STR. METHODS: Fifty-nine primary AMs after STR were examined for
      predictors of progression, including the impact of SRS and EBRT, in a
      retrospective cohort study. RESULTS: Twenty-seven patients (46%) progressed after
      STR (median, 30 months). On univariate analysis, spontaneous necrosis positively
      (hazard ratio = 5.2; P = .006) and adjuvant radiation negatively (hazard ratio =
      0.3; P = .009) correlated with progression; on multivariate analysis, only
      adjuvant radiation remained independently significant (hazard ratio = 0.3; P =
      .006). SRS and EBRT were associated with greater local control (LC; P = .02) and
      progression-free survival (P = .007). The 2-, 5-, and 10-year actuarial LC rates
      after STR vs STR/EBRT were 60%, 34%, and 34% vs 96%, 65%, and 45%. The 2-, 5-,
      and 10-year actuarial progression-free survival rates after STR vs STR/EBRT were
      60%, 30%, and 26% vs 96%, 65%, and 45%. Compared with STR alone, adjuvant
      radiation therapy significantly improved LC in AMs that lack spontaneous necrosis
      (P = .003) but did not improve LC in AMs with spontaneous necrosis (P = .6).
      CONCLUSION: Adjuvant SRS or EBRT improved LC of AMs after STR but only for tumors
      without spontaneous necrosis. Spontaneous necrosis may aid in decisions to
      administer adjuvant SRS or EBRT after STR of AMs.

PMID- 24932709
TI  - Large pontine cavernous malformations: resection via the telovelar approach and
      mapping of the fourth ventricular floor: 3-dimensional operative video.

PMID- 24932710
TI  - The history of neurosurgery at the University of Alabama at Birmingham.
AB  - : The Division of Neurosurgery at the University of Alabama at Birmingham was
      formally founded in 1954 under the leadership of James Garber Galbraith. The
      following 60 years would see neurosurgery at the forefront of the development of
      a nationally recognized medical center in the heart of Birmingham, Alabama. The
      Department of Neurosurgery now employs 14 faculty members, performs more than
      4500 neurosurgical procedures annually, is active in clinical and laboratory
      research, and boasts a contemporary, comprehensive residency training program.

PMID- 24932711
TI  - Mechanism of 2-hydropropyl-beta-cyclodextrin in the stabilization of frozen
      formulations.
AB  - Freezing of commonly used parenteral products to increase pharmaceutical
      stability for cost-saving purposes is a common practice in patient care. However,
      frozen meropenem, a model drug, in saline has a shelf life of less than a month
      due to the low glass transition temperature (Tg'): below -40 degrees C. When
      meropenem is formulated with the 2-hydroxypropyl-beta-cyclodextrin (HPBC) the
      shelf life (?90% potency) is extrapolated to be greater than one year at -25
      degrees C based on data for storage at 6months. The mechanisms that may explain
      meropenem-HPBC formulation frozen stability include vitrification and/or
      formation of an inclusion complex. Although NMR data indicated complexation of
      meropenem by HPBC in a ratio of 0.6:1, inclusion was unlikely to be the mechanism
      as stability was not extended to the thawed solutions. Therefore, vitrification
      is concluded to be the stabilization mechanism. The Tg' for meropenem-HPBC
      (13.3%) formulation at pH 7.9 was -17.75 degrees C which was similar to that of a
      meropenem solution formulated with a known vitrifying agent, Dextran 40. This
      higher Tg' for HPBC was unexpected based on trends predicted by the Fox-Flory
      equation. Trial formulations containing either Dextran 1, Dextran 40,
      hydroxyethyl starch, or sulfobutyl-beta-cyclodextrin heptasodium (Captisol(r))
      were also unable to stabilize meropenem as the Tg' values were below the frozen
      storage temperature. Upon 6-month storage, potency losses were -3.0% and -7.7%
      for meropenem frozen premix formulated in 13.3% HPBC (pH 7.9) at -25 and -20
      degrees C storage, respectively; versus -31.2% and -60.8% for controls. Frozen
      premixes with high ionic strength (containing NaCl or Captisol(r)) and/or at pH
      7.3 were also found to be unstable. 

PMID- 24932712
TI  - Topological characterization of a bacterial cellulose-acrylic acid polymeric
      matrix.
AB  - This paper focuses on the micro- and nano-topological organization of a hydrogel,
      constituted by a mixture of bacterial cellulose and acrylic acid, and intended
      for biomedical applications. The presence of acrylic acid promotes the formation
      of two interpenetrated continuous phases: the primary "pores phase" (PP)
      containing only water and the secondary "polymeric network phase" (PNP)
      constituted by the polymeric network swollen by the water. Low field Nuclear
      Magnetic Resonance (LF NMR), rheology, Scanning Electron Microscopy (SEM) and
      release tests were used to determine the characteristics of the two phases. In
      particular, we found that this system is a strong hydrogel constituted by 81%
      (v/v) of PP phase the remaining part being occupied by the PNP phase. Pores
      diameters span in the range 10-100 MUm, the majority of them (85%) falling in the
      range 30-90 MUm. The high PP phase tortuosity indicates that big pores are not
      directly connected to each other, but their connection is realized by a series of
      interconnected small pores that rend the drug path tortuous. The PNP is
      characterized by a polymer volume fraction around 0.73 while mesh size is around
      3 nm. The theoretical interpretation of the experimental data coming from the
      techniques panel adopted, yielded to the micro- and nano-organization of our
      hydrogel.

PMID- 24932713
TI  - Framework for engineering finite state machines in gene regulatory networks.
AB  - Finite state machines are fundamental computing devices at the core of many
      models of computation. In biology, finite state machines are commonly used as
      models of development in multicellular organisms. However, it remains unclear to
      what extent cells can remember state, how they can transition from one state to
      another reliably, and whether the existing parts available to the synthetic
      biologist are sufficient to implement specified finite state machines in living
      cells. Furthermore, how complex multicellular behaviors can be realized by
      multiple cells coordinating their states with signaling, growth, and division is
      not well understood. Here, we describe a method by which any finite state machine
      can be built using nothing more than a suitably engineered network of readily
      available repressing transcription factors. In particular, we show the
      mathematical equivalence of finite state machines with a Boolean model of gene
      regulatory networks. We describe how such networks can be realized with a small
      class of promoters and transcription factors. To demonstrate the effectiveness of
      our approach, we show that the behavior of the coarse grained ideal Boolean
      network model approximates a fine grained delay differential equation model of
      gene expression. Finally, we explore a framework for the design of more complex
      systems via an example, synthetic bacterial microcolony edge detection, that
      illustrates how finite state machines could be used together with cell signaling
      to construct novel multicellular behaviors. 

PMID- 24932714
TI  - Duration of melatonin regulates seasonal plasticity in subtropical Indian weaver
      bird, Ploceus philippinus.
AB  - Day length regulates seasonal plasticity connected with reproduction in birds.
      Rhythmic pineal melatonin secretion is a reliable indicator of the night length,
      hence day length. Removal of rhythmic melatonin secretion by exposure to constant
      bright light (LLbright) or by pinealectomy renders several species of songbirds
      including Indian weaver bird (Ploceus philippinus) arrhythmic. Present study
      investigated whether rhythmic melatonin is involved in the regulation of key
      reproductive neuropeptides (GnRH I and GnIH) and reproduction linked neural
      changes, viz. song control nuclei, in Indian weaver birds. Two experiments were
      performed using birds in an arrhythmic condition with low (under LLbright) or no
      (in the absence of pineal gland) endogenous melatonin. In experiment I, three
      groups of birds (n=5 each) entrained to 12L:12D were exposed to LLbright (25lux)
      for two weeks. Beginning on day 15 of LLbright, a control group received vehicle
      for 16h and two treatment groups were given melatonin in drinking water for 8h or
      16h. In experiment II, one group of sham-operated and three groups of
      pinealectomized birds (n=5 each) entrained to 12L:12D were exposed to constant
      dim light (LLdim, 0.5lux). Beginning on day 15 of LLdim, three groups received
      similar treatment as in experiment I. Birds were perfused after thirty cycles of
      the melatonin treatment, and brain sections were immunohistochemically double
      labeled for GnRH I and GnIH or Nissl stained. Activity was recorded throughout
      the experiments, while body mass and testes were measured at the beginning and
      end of the experiment. Birds were synchronized with melatonin cycles and measured
      the duration of melatonin as "night". Pinealectomized birds that received 16h of
      melatonin had significantly higher GnIH-ir cells than those received 8h
      melatonin; there was no difference in the GnRH I immunoreactivity between two
      treatment groups however. Intact birds that received long duration melatonin
      cycles exhibited small song control nuclei, specifically the high vocal center
      (HVC) and the robust nucleus of the arcopallium (RA), while birds that received
      short duration melatonin or no melatonin exhibited large HVC and RA. Thus,
      melatonin possibly regulates seasonal reproduction via GnIH secretion, and also
      controls seasonal neuroplasticity in the song control system in songbirds. 

PMID- 24932715
TI  - Leptin expression is rhythmic in brain and liver of goldfish (Carassius auratus).
      Role of feeding time.
AB  - Daily rhythms of feeding regulators are currently arousing research interest due
      to the relevance of the temporal harmony of endocrine regulators for growth and
      welfare in vertebrates. However, it is unknown the leptin circadian pattern in
      fish. The aim of this study is to investigate if leptin (gLep-aI and gLep-aII)
      expression is rhythmic in goldfish (Carassius auratus) liver and brain, and if
      such rhythms are driven by feeding time through a food entrainable oscillator.
      Fish maintained under 12-h light:12-h dark photoperiod and a scheduled feeding
      time showed 24-h locomotor activity and glycaemia rhythms. Moreover, hepatic gLep
      aI and brain gLep-aI and gLep-aII expression were rhythmic with different daily
      profiles, showing a postprandial increase of leptin expression in the liver but
      not in the brain. Under constant light and different feeding regimes (scheduled
      fed at 10:00, 22:00 or randomly fed), feeding time synchronized daily rhythms in
      locomotor activity, glycaemia and clock gene expression (gPer1a, gPer3 and
      gCry3), but the rhythmic expression of hepatic gLep-aI and brain gLep-aII only
      remained in fed fish at 10:00. In summary, daily rhythms of leptin expression in
      goldfish are differently regulated at central and peripheral level, and they are
      not directly driven by clock genes. The role of food entrained oscillators on
      leptin expression rhythms in fish remains to be demonstrated.

PMID- 24932716
TI  - The epidemiology and outcomes of infective endocarditis in a tertiary care
      hospital in Oman.
AB  - OBJECTIVES: We undertook this study to describe the epidemiological and clinical
      features of infective endocarditis (IE) and to study the complications and
      management of IE in a tertiary care hospital in Oman. METHODS: This is a
      retrospective study of 58 adult patients (>13 years of age) admitted to the Royal
      Hospital with IE from June 2006 to June 2011. RESULTS: Of the 58 patients, 40
      (69%) were males, and 18 (31%) were females (ratio 2.2). The median age was 43.6
      years (range: 14-85). Forty-eight cases (82.7%) had native valves, nine patients
      (15.6%) had prosthetic valves, and one case (1.7%) had a pacemaker. The most
      commonly involved valves were mitral (33, 56.9%) and aortic (23, 39.7%). The
      blood cultures were positive in 47 (81%) patients, and the most commonly isolated
      organisms were Streptococci spp., which were found in 20 (34.5%) patients, and
      Staphylococci spp., which were found in 19 (32.8%) patients. The complication
      rate was 21%. A total of 15 (25.9%) patients underwent surgical intervention, and
      the in-hospital mortality rate was 27.6%. CONCLUSIONS: Native-valve IE is the
      predominant type of endocarditis and is more of an acute disease. The prevalence
      of Staphylococci spp. IE is similar to that of Streptococci spp. IE, and its
      associated mortality remains high.

PMID- 24932717
TI  - Surface sediments in the marsh-sandy land transitional area: sandification in the
      western Songnen Plain, China.
AB  - The development of sandification process was studied, by monitoring the changes
      of sediment characteristics, at marsh-sandy land intersections in China's Songnen
      region. A series of sediment collection plates were deployed in the region; after
      one year, sediments in these plates were analyzed for changes of mass and
      chemical characteristics. The sediment flux and the sand content of the sediments
      decreased with the increasing longitudinal distance between the sampling site and
      the centre line of a sand dune. The mean sediment flux was 29 +/- 14 kg m(-2) yr(
      1) and 0.6 +/- 0.3 kg m(-2) yr(-1) in the sandy land and marsh, respectively.
      Strong, positive correlations were found between the concentrations of organic
      matter, total nitrogen, P, Fe, Ti, V and Zr, all of which were also negatively
      correlated with the sand content. The concentrations of organic matter, total
      nitrogen, P, Fe, Ti, V and Zr in the marsh sediment samples were all
      significantly greater than the corresponding concentrations of the sandy land
      (p<0.001). Sand content and Ti, V and Zr concentrations all proved to be valid
      indicators of sandification intensity, and they showed that the marsh could be
      divided into three distinct zones. Sand expansion extended about 88 m into the
      marsh. The mean sand content in the sediments of the sandy land was 91% and then
      64% in the marsh, which in turn was higher than that of marshes outside the
      influence of sandification, suggesting that the marsh in the marsh-sandy land
      transitional area has already undergone extensive sandification in the past. The
      study results provide information on the wetland's function of indicating and
      buffering the sandification process.

PMID- 24932719
TI  - Development of multilayer microcapsules by a phase coacervation method based on
      ionic interactions for textile applications.
AB  - The present study describes the development of multilayer microcapsules by 11
      alternate additions of chitosan (Chi) and sodium dodecyl sulfate (SDS) in a
      combined emulsification and phase coacervation method based on ionic
      interactions. After an alkali treatment, microcapsules are applied on polyester
      (PET) fabric by a padding process to investigate their wash-durability on fabric.
      Air atmospheric plasma treatment is performed on PET fabric to modify the surface
      properties of the textiles. Zeta potential, X-ray photoelectron spectroscopy
      (XPS), wetting measurements, scanning electron microscopy (SEM), and atomic force
      microscopy (AFM) with surface roughness measurements are realized to characterize
      and determine wash durability of microcapsule samples onto PET. After alkali
      treatment, the microcapsules are selected for textile application because they
      are submicron sized with the desired morphology. The results obtained from
      various characterization techniques indicate that microcapsules are wash-durable
      on PET fabric pre activated by air plasma atmospheric as Chi based microcapsules
      can interact directly with PET by ionic interactions. 

PMID- 24932720
TI  - Convergence angles of metal ceramic crowns prepared by dental students.
AB  - STATEMENT OF PROBLEM: Convergence angles of crown preparations achieved by dental
      students vary from the recommended angles and depend on many variables and
      factors. Sex of operators and examination conditions in which preparations were
      made have not been reported in the literature. PURPOSE: The purpose of this study
      was to determine the mean convergence angles produced by fifth-year dental
      students at King Abdulaziz University. MATERIAL AND METHODS: Maxillary first
      premolar abutment preparations for metal ceramic restoration were made by fifth
      year dental students on typodonts under preclinical examination conditions. A
      total of 68 preparations, made by 38 male and 30 female students, were randomly
      selected for evaluation of the buccolingual and mesiodistal convergence angles of
      each abutment tooth with an optical preparation scanner and digitizer to produce
      3-dimensional digital objects. Two-sided t tests were performed to compare the
      buccolingual and mesiodistal angles between the sexes. RESULTS: The mean
      mesiodistal angle of all preparations was 11.11 +/-4.79 degrees, and the mean
      buccolingual angle was 10.49 +/-3.95 degrees. The mean buccolingual angle in
      preparations by male students was 10.16 +/-3.90 degrees, compared with 11.46 +/
      5.06 degrees in preparations by female students. The mean mesiodistal angle was
      10.92 +/-4.03 degrees in preparations by male students, compared to 10.66 +/-4.45
      degrees in preparations by female students. No statistical difference was
      observed between the sexes for either angle (buccolingual, P=.435; mesiodistal,
      P=.497). The smallest and largest angles observed were 2.59 and 24.64 degrees.
      Approximately 12% of male students and 10% of female students made preparations
      with less than a 6-degree (ideal convergence angle) buccolingual or mesiodistal
      angle. CONCLUSIONS: The average convergence angles produced were between 10.16
      and 11.46 degrees. Several students were able to achieve ideal convergence
      angles. Male and female students achieved similar buccolingual and mesiodistal
      convergence angles.

PMID- 24932721
TI  - Improving the tolerance of Escherichia coli to medium-chain fatty acid
      production.
AB  - Microbial fatty acids are an attractive source of precursors for a variety of
      renewable commodity chemicals such as alkanes, alcohols, and biofuels. Rerouting
      lipid biosynthesis into free fatty acid production can be toxic, however, due to
      alterations of membrane lipid composition. Here we find that membrane lipid
      composition can be altered by the direct incorporation of medium-chain fatty
      acids into lipids via the Aas pathway in cells expressing the medium-chain
      thioesterase from Umbellularia californica (BTE). We find that deletion of the
      aas gene and sequestering exported fatty acids reduces medium-chain fatty acid
      toxicity, partially restores normal lipid composition, and improves medium-chain
      fatty acid yields. 

PMID- 24932723
TI  - Spatial orienting following dynamic cues in infancy: grasping hands versus
      inanimate objects.
AB  - Movement perception facilitates spatial orienting of attention in infants
      (Farroni, Johnson, Brockbank, & Simion, 2000). In a series of 4 experiments, we
      investigated how orienting of attention in infancy is modulated by dynamic
      stimuli. Experiment 1 (N = 36) demonstrated that 5-month-olds as well as 7-month
      olds orient to the direction of a dynamically grasping human hand. Experiment 2
      (N = 36) showed that 7-month-olds orient covertly to direction of a geometrical
      shape moving on the trajectory of the grasping movement, but 5-month-olds do not.
      Experiment 3 (N = 18) showed that mere linear translating object movement does
      not elicit covert orienting of attention in 7-month-olds. In Experiment 4 (N =
      18), we found that 7-month-olds process both grasping direction and movement
      direction, which resulted in increased reaction times when these cues conflicted.
      These findings suggest that orienting of attention reflects rapid detection of
      goal-directed agents. Five-month-olds need the information of both movement and
      grasping direction, whereas 7-month-olds can use each of these directional cues
      in isolation.

PMID- 24932722
TI  - Parent relationship quality buffers against the effect of peer stressors on
      depressive symptoms from middle childhood to adolescence.
AB  - During the transition to adolescence, several developmental trends converge to
      increase the importance of peer relationships, the likelihood of peer-related
      stressors, and the experience of depressive symptoms. Simultaneously, there are
      significant changes in parent-child relationships. The current study sought to
      evaluate whether positive relationship quality with parents continued to serve a
      protective effect by buffering the relationship between stressful life events,
      especially peer stress, and increases in depressive symptoms throughout the
      transition to adolescence. Participants in a large (N = 692) 2-site accelerated
      longitudinal study were recruited in 3rd, 6th, and 9th grade and followed every 3
      months for 1 year. At baseline, parents and youth reported on parent-child
      relationship quality, and every 3 months thereafter reported on their levels of
      stressors and depressive symptoms. Parent relationship quality moderated the
      relationship of person-level fluctuations in peer stressors, such that there was
      a stronger association between peer stressors and increases in depressive
      symptoms in youth with lower levels of positive parental relationship quality.
      This effect was specific to peer stressors. These results suggest that low levels
      of parent relationship quality leave youth particularly vulnerable to the
      depressogenic effects of peer stressors from childhood through adolescence.

PMID- 24932724
TI  - Probability versus representativeness in infancy: can infants use naive physics
      to adjust population base rates in probabilistic inference?
AB  - A rich tradition in developmental psychology explores physical reasoning in
      infancy. However, no research to date has investigated whether infants can reason
      about physical objects that behave probabilistically, rather than
      deterministically. Physical events are often quite variable, in that similar
      looking objects can be placed in similar contexts with different outcomes. Can
      infants rapidly acquire probabilistic physical knowledge, such as some leaves
      fall and some glasses break by simply observing the statistical regularity with
      which objects behave and apply that knowledge in subsequent reasoning? We taught
      11-month-old infants physical constraints on objects and asked them to reason
      about the probability of different outcomes when objects were drawn from a large
      distribution. Infants could have reasoned either by using the perceptual
      similarity between the samples and larger distributions or by applying physical
      rules to adjust base rates and estimate the probabilities. Infants learned the
      physical constraints quickly and used them to estimate probabilities, rather than
      relying on similarity, a version of the representativeness heuristic. These
      results indicate that infants can rapidly and flexibly acquire physical knowledge
      about objects following very brief exposure and apply it in subsequent reasoning.

PMID- 24932725
TI  - Genome-wide analysis of repeat diversity across the family Musaceae.
AB  - BACKGROUND: The banana family (Musaceae) includes genetically a diverse group of
      species and their diploid and polyploid hybrids that are widely cultivated in the
      tropics. In spite of their socio-economic importance, the knowledge of Musaceae
      genomes is basically limited to draft genome assemblies of two species, Musa
      acuminata and M. balbisiana. Here we aimed to complement this information by
      analyzing repetitive genome fractions of six species selected to represent
      various phylogenetic groups within the family. RESULTS: Low-pass sequencing of M.
      acuminata, M. ornata, M. textilis, M. beccarii, M. balbisiana, and Ensete
      gilletii genomes was performed using a 454/Roche platform. Sequence reads were
      subjected to analysis of their overall intra- and inter-specific similarities
      and, all major repeat families were quantified using graph-based clustering.
      Maximus/SIRE and Angela lineages of Ty1/copia long terminal repeat (LTR)
      retrotransposons and the chromovirus lineage of Ty3/gypsy elements were found to
      make up most of highly repetitive DNA in all species (14-34.5% of the genome).
      However, there were quantitative differences and sequence variations detected for
      classified repeat families as well as for the bulk of total repetitive DNA. These
      differences were most pronounced between species from different taxonomic
      sections of the Musaceae family, whereas pairs of closely related species (M.
      acuminata/M. ornata and M. beccarii/M. textilis) shared similar populations of
      repetitive elements. CONCLUSIONS: This study provided the first insight into the
      composition and sequence variation of repetitive parts of Musaceae genomes. It
      allowed identification of repetitive sequences specific for a single species or a
      group of species that can be utilized as molecular markers in breeding programs
      and generated computational resources that will be instrumental in repeat masking
      and annotation in future genome assembly projects.

PMID- 24932726
TI  - Hydrophilization of poly(caprolactone) copolymers through introduction of
      oligo(ethylene glycol) moieties.
AB  - In this study, a new family of poly(epsilon-caprolactone) (PCL) copolymers that
      bear oligo(ethylene glycol) (OEG) moieties is described. The synthesis of three
      different oligo(ethylene glycol) functionalized epoxide monomers derived from 2
      methyl-4-pentenoic acid, and their copolymerization with epsilon-caprolactone
      (CL) to poly(CL-co-OEG-MPO) copolymers is presented. The statistical
      copolymerization initiated with SnOct2/BnOH yielded the copolymers with varying
      OEG content and composition. The linear relationship between feed ratio and
      incorporation of the OEG co-monomer enables control over backbone functional
      group density. The introduction of OEG moieties influenced both the thermal and
      the hydrophilic characteristics of the copolymers. Both increasing OEG length and
      backbone content resulted in a decrease in static water contact angle. The
      introduction of OEG side chains in the PCL copolymers had no adverse influence on
      MC-3TE3-E1 cell interaction. However, changes to cell form factor (Phi) were
      observed. While unmodified PCL promoted elongated (anisotropic) morphologies (Phi
      = 0.094), PCL copolymer with tri-ethylene glycol side chains at or above seven
      percent backbone incorporation induced more isotropic cell morphologies (Phi =
      0.184) similar to those observed on glass controls (Phi = 0.151). 

PMID- 24932727
TI  - Hydrographic processes driven by seasonal monsoon system affect siphonophore
      assemblages in tropical-subtropical waters (western North Pacific Ocean).
AB  - This work is a part of the Taiwan Cooperative Oceanic Fisheries Investigation,
      the first large scale hydrographic and plankton survey around Taiwan (21-26
      degrees N, 119-123 degrees E). The present study examined the influence of
      hydrodynamic and biological variables driven by monsoon system on the
      siphonophore assemblages through an annual cycle in 2004. Calycophorans, namely
      Chelophyes appendiculata, Diphyes chamissonis, Lensia subtiloides, Bassia
      bassensis, and Muggiaea atlantica, were the most dominant siphonophore species.
      Maximum abundance of these dominant species generally occurred during the warm
      period (May and August), while M. atlantica had a significantly peak abundance in
      February. Although no apparently temporal difference in siphonophore abundance
      was observed in the study, siphonophore assemblage was more diverse in August
      than in other sampling times. Result of a cluster analysis indicated that
      assemblage structure of siphonophores in the waters around Taiwan varied at
      temporal and spatial scales during the sampling period. The intrusions of the
      Kuroshio Branch Current and China Coastal Current to the study area play an
      important role on the transportation of siphonophores. Also, the distribution of
      siphonophore assemblage was closely related to the hydrographic characteristics,
      with temperature, chlorophyll a concentration, and zooplankton abundance being
      the major environmental factors affecting the spatio-temporal variability of
      siphonophores. This study contributes substantially to the new knowledge of the
      siphonophore assemblage in the tropical-temperate waters of Taiwan. 

PMID- 24932728
TI  - ELN gene triplication responsible for familial supravalvular aortic aneurysm.
AB  - Supravalvular aortic aneurysms are less frequent than abdominal ones. Among
      Supravalvular aortic aneurysm aetiologies, we focused on dystrophic lesions as
      they can be secondary to genetic causes such as elastin anomaly. We report on a
      familial 7q11.23 triplication - including the ELN gene - segregating with a
      supravalvular aortic aneurysm. During her first pregnancy, our index patient was
      diagnosed with tuberous sclerosis and with a Supravalvular aortic aneurysm. The
      foetus was affected equally. For the second pregnancy, parents applied for
      preimplantation diagnosis, and a subsequent prenatal diagnosis was offered to the
      couple, comprising TSC1 molecular analysis, karyotype, and multiplex ligation
      probe amplification. TSC1 mutation was not found on foetal deoxyribo nucleic
      acid. Foetal karyotype was normal, but multiplex ligation probe amplification
      detected a 7q11.23 duplication. Quantitative-polymerase chain reaction and array
      comparative genomic hybridisation carried out to further assess this chromosome
      imbalance subsequently identified a 7q11.23 triplication involving ELN and LIMK1.
      Foetal heart ultrasound identified a Supravalvular aortic aneurysm. A familial
      screening was offered for the 7q11.23 triplication and, when found, heart
      ultrasound was performed. The triplication was diagnosed in our index case as
      well as in her first child. Of the 17 individuals from this family, 11 have the
      triplication. Of the 11 individuals with the triplication, 10 were identified to
      have a supravalvular aortic aneurysm. Of them, two individuals received a medical
      treatment and one individual needed surgery. We provide evidence of supravalvular
      aortic aneurysm segregating with 7q11.23 triplication in this family. We would
      therefore recommend cardiac surveillance for individuals with 7q11.23
      triplication. It would also be interesting to offer a quantitative-polymerase
      chain reaction or an array-comparative genomic hybridisation to a larger cohort
      of patients presenting with isolated supravalvular aortic aneurysm, as it may
      provide further information. 

PMID- 24932729
TI  - Genetic and ecological outcomes of Inga vera subsp. affinis (Leguminosae) tree
      plantations in a fragmented tropical landscape.
AB  - Planting of native trees for habitat restoration is a widespread practice, but
      the consequences for the retention and transmission of genetic diversity in
      planted and natural populations are unclear. Using Inga vera subsp. affinis as a
      model species, we genotyped five natural and five planted populations in the
      Atlantic forest of northeastern Brazil at polymorphic microsatellite loci. We
      studied the breeding system and population structure to test how much genetic
      diversity is retained in planted relative to natural populations. We then
      genotyped seedlings from these populations to test whether genetic diversity in
      planted populations is restored by outcrossing to natural populations of I. vera.
      The breeding system of natural I. vera populations was confirmed to be highly
      outcrossing (t = 0.92; FIS = -0.061, P = 0.04), with populations showing weak
      population substructure (FST = 0.028). Genetic diversity in planted populations
      was 50% less than that of natural populations (planted: AR = 14.9, HO = 0.865 and
      natural: AR = 30.8, HO = 0.655). However, seedlings from planted populations
      showed a 30% higher allelic richness relative to their parents (seedlings AR =
      10.5, parents AR = 7.6). Understanding the processes and interactions that shape
      this system are necessary to provide ecologically sensible goals and successfully
      restore hyper-fragmented habitats. Future restoration plans for I. vera must
      consider the genetic diversity of planted populations and the potential for gene
      flow between natural populations in the landscape, in order to preserve
      ecological interactions (i.e. pollination), and promote opportunities for
      outcrossing.

PMID- 24932731
TI  - Persistence of Toxoplasma gondii tissue stages in poultry over a conventional
      fattening cycle.
AB  - Toxoplasma gondii is a widely spread protozoon in humans, mammals and poultry.
      Regarding the latter, nothing is known yet about the duration of T. gondii
      persistence and distribution over a conventional fattening cycle of turkeys and
      chickens. Twenty-four turkeys and 12 broiler chickens were infected intravenously
      with 1*10(6) T. gondii tachyzoites (strain NED). Serum antibody levels were
      determined weekly by ELISA (turkeys) or immunofluorescent antibody test
      (chickens). Turkeys were slaughtered at 4, 8, 12 and 16 weeks post-infection
      (p.i.), and chickens 5 or 10 weeks p.i. (n = 6 per group). Sixteen different
      tissue samples per bird were analysed for T. gondii by PCR. All infected animals
      showed seroconversion. In turkeys, 15.9% of all samples were tested positive for
      T.-gondii-DNA. Among the edible tissues (drumstick, thigh, breast muscle, heart,
      liver and gizzard) 7.8% tested positive. Among poultry slaughtered after
      different periods of time after infection no significant differences (P>0.05)
      regarding the number of positive samples were observed. Only 4 out of 192 samples
      (2.1%) from infected chickens contained detectable T. gondii DNA.The PCR findings
      suggested that T. gondii may persist in poultry. Particularly in turkey it was
      shown that edible tissues stay infected for at least 16 weeks p.i. which
      indicates a potential risk for consumers of undercooked turkey meat whereas
      chickens appear less susceptible to T. gondii infection.

PMID- 24932730
TI  - Chondroitin sulfate proteoglycan CSPG4 as a novel hypoxia-sensitive marker in
      pancreatic tumors.
AB  - CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed
      whether the shed ectodomain of CSPG4 (sCSPG4) might circulate and reflect
      potential changes in CSPG4 tissue expression (pCSPG4) due to desmoplastic and
      malignant aberrations occurring in pancreatic tumors. Serum sCSPG4 was measured
      using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors
      (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms:
      benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic
      IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14;
      ductal adenocarcinomas, n = 35+86). Pancreatic pCSPG4 expression was evaluated
      using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. sCSPG4
      was found in circulation, but its level was significantly lower in pancreatic
      patients than in donors. Selective maintenance was observed in advanced IPMNs and
      PDACs and showed a nodal association while lacking prognostic relevance.
      Pancreatic pCSPG4 expression was preserved or elevated, whereby neoplastic cells
      lacked pCSPG4 or tended to overexpress without shedding. Extreme pancreatic
      overexpression, membranous exposure and tissue(high)/sera(low)-discordance
      highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic
      markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which
      pVHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing
      confined pCSPG4 overexpression to normal mesenchymal but not epithelial cells,
      and a third of tested carcinoma cell lines; however, only the latter showed
      pCSPG4-responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce
      the malignant potential of either normoxic or hypoxic cells. Thus, overexpression
      of the newly established conditional hypoxic indicator, CSPG4, is apparently non
      pathogenic in pancreatic malignancies but might mark distinct epithelial lineage
      and contribute to cell polarity disorders. Surficial retention on tumor cells
      renders CSPG4 an attractive therapeutic target. Systemic 'drop and restoration'
      alterations accompanying IPMN and PDAC progression indicate that the interference
      of pancreatic diseases with local and remote shedding/release of sCSPG4 into
      circulation deserves broad diagnostic exploration.

PMID- 24932732
TI  - Vitamin D status and its determinants in children and adults among families in
      late summer in Denmark.
AB  - The impact of the familial relationship on vitamin D status has not been
      investigated previously. The objective of the present cross-sectional study was
      to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants
      in children and adults among families in late summer in Denmark (56 degrees N).
      Data obtained from 755 apparently healthy children (4-17 years) and adults (18-60
      years) recruited as families (n 200) in the VitmaD study were analysed. Blood
      samples were collected in September-October, and serum 25(OH)D concentration was
      measured by liquid chromatography-tandem MS. Information on potential
      determinants was obtained using questionnaires. The geometric mean serum 25(OH)D
      concentration was 72.1 (interquartile range 61.5-86.7) nmol/l (range 9-162
      nmol/l), with 9 % of the subjects having 25(OH)D concentrations < 50 nmol/l. The
      intra-family correlation was 0.27 in all subjects, 0.24 in the adults and 0.42 in
      the children. Serum 25(OH)D concentration was negatively associated with BMI (P<
      0.001) and positively associated with dietary vitamin D intake (P= 0.008),
      multivitamin use (P= 0.019), solarium use (P= 0.006), outdoor stay (P= 0.001),
      sun preference (P= 0.002) and sun vacation (P< 0.001), but was not associated
      with lifestyle-related factors in the adults when these were assessed together
      with the other determinants. In conclusion, the majority of children and adults
      among the families had serum 25(OH)D concentrations >50 nmol/l in late summer in
      Denmark. Both dietary and sun-related factors were determinants of vitamin D
      status and the familial component was stronger for the children than for the
      adults.

PMID- 24932733
TI  - Structure-induced enhancement of thermal conductivities in electrospun polymer
      nanofibers.
AB  - Polymers that are thermally insulating in bulk forms have been found to exhibit
      higher thermal conductivities when stretched under tension. This enhanced heat
      transport performance is believed to arise from the orientational alignment of
      the polymer chains induced by tensile stretching. In this work, a novel high
      sensitivity micro-device platform was employed to determine the axial thermal
      conductivity of individual Nylon-11 polymer nanofibers fabricated by
      electrospinning and post-stretching. Their thermal conductivity showed a
      correlation with the crystalline morphology measured by high-resolution wide
      angle X-ray scattering. The relationship between the nanofiber internal
      structures and thermal conductivities could provide insights into the
      understanding of phonon transport mechanisms in polymeric systems and also guide
      future development of the fabrication and control of polymer nanofibers with
      extraordinary thermal performance and other desired properties. 

PMID- 24932734
TI  - Prehospital Transfusion of Plasma and Red Blood Cells in Trauma Patients.
AB  - Abstract Objective. Earlier use of plasma and red blood cells (RBCs) has been
      associated with improved survival in trauma patients with substantial hemorrhage.
      We hypothesized that prehospital transfusion (PHT) of thawed plasma and/or RBCs
      would result in improved patient coagulation status on admission and survival.
      Methods. Adult trauma patient records were reviewed for patient demographics,
      shock, coagulopathy, outcomes, and blood product utilization from September 2011
      to April 2013. Patients arrived by either ground or two different helicopter
      companies. All patients transfused with blood products (either pre- or in
      hospital) were included in the study. One helicopter system (LifeFlight, LF) had
      thawed plasma and RBCs while the other air (OA) and ground transport systems used
      only crystalloid resuscitation. Patients receiving PHT were compared with all
      other patients meeting entry criteria to the study cohort. All comparisons were
      adjusted in multilevel regression models. Results. A total of 8,536 adult trauma
      patients were admitted during the 20-month study period, of which 1,677 met
      inclusion criteria. They represented the most severely injured patients (ISS = 24
      and mortality = 26%). There were 792 patients transported by ground, 716 by LF,
      and 169 on OA. Of the LF patients, 137 (19%) received prehospital transfusion.
      There were 942 units (244 RBCs and 698 plasma) placed on LF helicopters, with
      1.9% wastage. PHT was associated with improved acid-base status on hospital
      admission, decreased use of blood products over 24 hours, a reduction in the risk
      of death in the sickest patients over the first 6 hours after admission, and
      negligible blood products wastage. In this small single-center pilot study, there
      were no differences in 24-hour (odds ratio 0.57, p = 0.117) or 30-day mortality
      (odds ratio 0.71, p = 0.441) between LF and OA. Conclusions. Prehospital plasma
      and RBC transfusion was associated with improved early outcomes, negligible blood
      products wastage, but not an overall survival advantage. Similar to the data
      published from the ongoing war, improved early outcomes are associated with
      placing blood products prehospital, allowing earlier infusion of life-saving
      products to critically injured patients.

PMID- 24932735
TI  - Coxsackievirus A6 associated hand, foot and mouth disease in adults: clinical
      presentation and review of the literature.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) is generally considered a rare
      illness in adults. Classically, HFMD has been strongly associated with
      coxsackievirus strain A16 and enterovirus 71. The coxsackievirus A6 (CVA6) strain
      has been linked to severe worldwide outbreaks since 2008. CVA6 is associated with
      a more severe and profound course of disease, affecting both children and adults.
      OBJECTIVES: To present a series of five adult patients diagnosed with HFMD due to
      CVA6. We investigate method of diagnosis and compare clinical presentation of
      adult cases to those in children. STUDY DESIGN: Each patient underwent a full
      body skin exam as well as inspection of the oral cavity. Rapid plasma reagin
      (RPR) and serologic assays by complement fixation against coxsackievirus B (1-6)
      and A (2,4,7,9,10,16) were performed as indicated. As standard serological
      testing does not detect CVA6, real-time reverse transcription-polymerase chain
      reaction (qRT-PCR) of serum, buccal swabs, and skin scrapings were performed by
      the Centers for Disease Control and Prevention (CDC). RESULTS: Each patient had
      clinical findings consistent with various stages of HFMD. One patient presented
      with delayed onychomadesis and desquamation of the palms and soles. RPR and
      serologic assays by complement fixation against CVB (1-6) and CVA (2,4,7,9,10,16)
      were mostly negative, although elevated in two patients due to cross-reactivity.
      qRT-PCR identified CVA6 genetic material in samples from all patients.
      CONCLUSION: This series demonstrates that there is a wide array of disease
      presentation of CVA6 associated HFMD in adults.

PMID- 24932736
TI  - Association of dolutegravir and rilpivirine, enhanced by foscarnet induction, in
      effective salvage antiretroviral therapy.
AB  - We report the case of a multi-experienced patient, infected with an HIV-1 strain,
      with selected multiple resistance mutations. We designed a novel well-tolerated
      and effective rescue treatment including dolutegravir, rilpivirine, and
      foscarnet, allowing a 60-week sustained virological response for the first time
      in 23 years of HIV infection. 

PMID- 24932737
TI  - Evaluation of the Bio-Rad Geenius HIV-1/2 test as a confirmatory assay.
AB  - OBJECTIVES: We have evaluated the recently Conformite Europeenne (CE)-marked Bio
      Rad Geenius human immunodeficiency virus (HIV)1/2 as a rapid and simple
      alternative to western blot for confirmation of HIV screening results. METHODS: A
      total of 160 serum samples were tested: 44 HIV-1 reactive samples by a fourth
      generation Murex HIV Ag/Ab and/or Vidas HIV Duo Ultra, five HIV-2 reactive
      samples, 15 HIV-1 non-B subtype samples and 11 confirmed HIV-1 early
      seroconversion samples, 72 nonreactive samples, eight indeterminate samples by MP
      HIV BLOT 2.2 confirmed negative after follow-up and five low-reactive samples by
      enzyme immunoassay (EIA) negative by MP HIV BLOT 2.2. The samples were tested
      according to the manufacturer's guidelines. RESULTS: The overall sensitivity for
      Bio-Rad Geenius HIV1/2 assay was 92%. Five out of 11 early seroconversion samples
      were tested positive, four negative and two indeterminate. All HIV-1 non-B
      subtype samples were tested positive. Two out of the five HIV-2 reactive samples
      were tested positive HIV-2, two positive HIV-2 with HIV-1 cross-reaction and one
      HIV positive untypable. After excluding early seroconversion samples, the
      sensitivity of Bio-Rad Geenius HIV1/2 assay reached 100%. Overall specificity was
      96%. All HIV negative serums by fourth-generation EIA were tested negative. All
      five low-reactive samples by EIA, negative by HIV BLOT 2.2 were tested negative
      by Bio-Rad Geenius HIV1/2. Two out of the eight indeterminate samples by MP HIV
      BLOT 2.2 that were confirmed negative after follow-up were tested indeterminate
      and one invalid, the other five were negative. After excluding these last 13
      samples, the specificity of Bio-Rad Geenius HIV1/2 assay reached 100%. In
      comparison with MP HIV BLOT 2.2, the Bio-Rad Geenius HIV1/2 assay was markedly
      time saving, allowed full traceability, automatic reading and interpretation.
      CONCLUSIONS: The Bio-Rad Geenius HIV1/2 confirmatory system represents a reliable
      alternative to other confirmatory assays in HIV testing algorithms and provides
      clear improvement in quality management.

PMID- 24932738
TI  - Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis.
AB  - OBJECTIVE: Lipopolysaccharide (LPS) is a major component of the Neisseria
      meningitidis outer membrane. Here we report a patient with meningococcal
      meningitis of which the causative isolate lacked LPS. Thus far, no naturally
      occurring LPS-deficient meningococcal isolate has been known to cause clinical
      disease. METHODS: We used SDS-PAGE, silver staining and LPS-specific antibodies
      in whole cell ELISA to determine LPS presence in the causative isolate.
      Meningococcal whole genome sequencing was performed using Roche 454-sequencing.
      The N. meningitidis strain MC58 was used to compare all LPS biosynthesis
      associated genes. We compared growth characteristics of Escherichia coli
      transformed with a plasmid containing 2 lpxH types. RESULTS: The patient
      presented with isolated thunderclap headache. Analysis of the causative N.
      meningitidis showed no LPS. Whole genome sequencing revealed a mutation located
      in lpxH explaining LPS-deficiency. Expression of this lpxH variant in E. coli
      resulted in growth impairment compared to E. coli expressing the meningococcal
      wild type lpxH variant. In addition, inactivating lpxH in N. meningitidis H44/76
      by insertional inactivation with a kanamycin cassette resulted in a LPS-deficient
      phenotype. CONCLUSIONS: We describe invasive meningococcal disease caused by a
      naturally occurring LPS-deficient meningococcal isolate.

PMID- 24932739
TI  - Ability of horse anti-Tityus discrepans F(ab')2 ELISA assay to recognize Tityus
      discrepans venom toxins.
AB  - Anti-Tityus discrepans F(ab')2 ELISA recognition of T. discrepans toxins was
      measured with regression analysis and its slope called ELISA recognition value
      (ERv). Fractions containing toxins affecting mammal macrophages or Na(+)-channels
      have Ervs >19. Toxins affecting potassium channels or insect NaV channels have
      ERvs <10. Fractions including curarizing or antineoplasic peptides had ERvs <1.
      Erv increases in proportion to mammalian toxin toxicity rather than to toxin
      molecular mass. 

PMID- 24932740
TI  - Phosphodiesterase from Daboia russelli russelli venom: purification, partial
      characterization and inhibition of platelet aggregation.
AB  - Phosphodiesterases (PDEs) belong to a super-family of enzymes that have multiple
      roles in the metabolism of extracellular nucleotides and regulation of nucleotide
      based intercellular signalling. A PDE from Russell's viper (Daboia russelli
      russelli) venom (DR-PDE) was purified by gel filtration, ion exchange and
      affinity chromatographies. Homogeneity of the preparation was verified by SDS
      PAGE, SE-HPLC and mass spectrometry. It was free from 5'-nucleotidase, alkaline
      phosphatase and protease activities. Identity of the enzyme was ensured from
      partial sequence homology with other PDEs. DR-PDE was inactivated by polyvalent
      anti-venom serum and metal chelators. The enzyme was partially inhibited by the
      root extracts of four medicinal plants but remained unaffected by inhibitors of
      intracellular PDEs. DR-PDE hydrolyses ADP and thus, strongly inhibits ADP-induced
      platelet aggregation in human platelet rich plasma. This study leads to better
      understanding of a component of Russell's viper venom that affects homoeostatic
      system of the victim. 

PMID- 24932741
TI  - NF-kappaB plays a key role in microcystin-RR-induced HeLa cell proliferation and
      apoptosis.
AB  - Microcystins (MCs) are well-known cyanobacterial toxins produced in eutrophic
      waters and can act as potential carcinogens and have caused serious risk to human
      health. However, pleiotropic even paradoxical actions of cells exposure to MCs
      have been reported, and the mechanisms of MC-induced tumorigenesis and apoptosis
      are still unknown. In this study, we performed the first comprehensive in vitro
      investigation on carcinogenesis associated with nuclear factor kappa B (NF
      kappaB) and its downstream genes in HeLa cells (Human cervix adenocarcinoma cell
      line from epithelial cells) exposure to MC-RR. HeLa cells were treated with 0,
      20, 40, 60, and 80 ug/mL MC-RR for 4, 8, 12, and 24 h. HeLa cells presented
      dualistic responses to different doses of MCs. CCK8 assay showed that MC-RR
      exposure evidently enhanced cell viability of HeLa cells at lower MCs doses. Cell
      cycle and apoptosis analysis revealed that lower MCs doses promoted G1/S
      transition and cell proliferation while higher doses of MCs induced apoptosis,
      with a dose-dependent manner. Electrophoretic mobility shift assay (EMSA)
      revealed that MC-RR could increase/decrease NF-kappaB activity at lower/higher MC
      RR doses, respectively. Furthermore, the expression of NF-kappaB downstream
      target genes including c-FLIP, cyclinD1, c-myc, and c-IAP2 showed the same
      variation trend as NF-kappaB activity both at mRNA and protein levels, which were
      induced by lower doses of MC-RR and suppressed by higher doses. Our data verified
      for the first time that NF-kappaB pathway may mediate MC-induced cell
      proliferation and apoptosis and provided a better understanding of the molecular
      mechanism for potential carcinogenicity of MC-RR. 

PMID- 24932743
TI  - The human biology of the past.

PMID- 24932744
TI  - Unity in diversity: an overview of the genomic anthropology of India.
AB  - CONTEXT: India is considered a treasure for geneticists and evolutionary
      biologists due to its vast human diversity, consisting of more than 4500
      anthropologically well-defined populations (castes, tribes and religious groups).
      Each population differs in terms of endogamy, language, culture, physical
      features, geographic and climatic position and genetic architecture. These
      factors contributed to India-specific genetic variations which may be responsible
      for various common diseases in India and its migratory populations. As a result,
      interpretations of the origins and affinities of Indian populations as well as
      health and disease conditions require complex and sophisticated genetic analysis.
      Evidence of ancient human dispersals and settlements is preserved in the genome
      of Indian inhabitants and this has been extensively analysed in conventional and
      genomic analyses. OBJECTIVE AND METHODS: Using genomic analyses of STRs and Alu
      on a set of populations, this study estimates the level and extent of genetic
      variation and its implications. RESULTS: The results show that Indian populations
      have a higher level of unique genetic diversity which is structured by many
      social processes and geographical attributes of the country. CONCLUSION: This
      overview highlights the need to study the anthropological structure and
      evolutionary history of Indian populations while designing genomic and epigenomic
      investigations.

PMID- 24932742
TI  - A rationale to target the SWI/SNF complex for cancer therapy.
AB  - SWI/SNF is a multisubunit chromatin-remodeling complex that performs fundamental
      roles in gene regulation, cell lineage specification, and organismal development.
      Mutations that inactivate SWI/SNF subunits are found in nearly 20% of human
      cancers, which indicates that the proper functioning of this complex is necessary
      to prevent tumor formation in diverse tissues. Recent studies show that SWI/SNF
      mutant cancers depend on residual SWI/SNF complexes for their aberrant growth,
      thus revealing synthetic lethal interactions that could be exploited for
      therapeutic purposes. Other studies reveal that certain acute leukemias and small
      cell lung cancers, which lack SWI/SNF mutations, can be vulnerable to inhibition
      of the SWI/SNF ATPase subunit BRG1, whereas several normal and malignant cell
      types do not show this sensitivity. Here, we review the emerging evidence that
      implicates SWI/SNF as a tumor-dependency and candidate drug target in human
      cancer. 

PMID- 24932745
TI  - Reticulate evolution and the human past: an anthropological perspective.
AB  - CONTEXT: The evidence is mounting that reticulate (web-like) evolution has shaped
      the biological histories of many macroscopic plants and animals, including non
      human primates closely related to Homo sapiens, but the implications of this non
      hierarchical evolution for anthropological enquiry are not yet fully understood.
      When they are understood, the result may be a paradigm shift in evolutionary
      anthropology. OBJECTIVE/METHODS: This paper reviews the evidence for reticulated
      evolution in the non-human primates and human lineage. Then it makes the case for
      extrapolating this sort of patterning to Homo sapiens and other hominins and
      explores the implications this would have for research design, method and
      understandings of evolution in anthropology. RESULTS/CONCLUSION: Reticulation was
      significant in human evolutionary history and continues to influence societies
      today. Anthropologists and human scientists-whether working on ancient or modern
      populations-thus need to consider the implications of non-hierarchic evolution,
      particularly where molecular clocks, mathematical models and simplifying
      assumptions about evolutionary processes are used. This is not just a problem for
      palaeoanthropology. The simple fact of different mating systems among modern
      human groups, for example, may demand that more attention is paid to the
      potential for complexity in human genetic and cultural histories.

PMID- 24932746
TI  - Diagnosing Homo sapiens in the fossil record.
AB  - BACKGROUND: Diagnosing Homo sapiens is a critical question in the study of human
      evolution. Although what constitutes living members of our own species is
      straightforward, in the fossil record this is still a matter of much debate. The
      issue is complicated by questions of species diagnoses and ideas about the mode
      by which a new species is born, by the arguments surrounding the behavioural and
      cognitive separateness of the species, by the increasing appreciation of
      variation in the early African H. sapiens record and by new DNA evidence of
      hybridization with extinct species. METHODS AND RESULTS: This study synthesizes
      thinking on the fossils, archaeology and underlying evolutionary models of the
      last several decades with recent DNA results from both H. sapiens and fossil
      species. CONCLUSION: It is concluded that, although it may not be possible or
      even desirable to cleanly partition out a homogenous morphological description of
      recent H. sapiens in the fossil record, there are key, distinguishing
      morphological traits in the cranium, dentition and pelvis that can be usefully
      employed to diagnose the H. sapiens lineage. Increasing advances in retrieving
      and understanding relevant genetic data provide a complementary and perhaps
      potentially even more fruitful means of characterizing the differences between H.
      sapiens and its close relatives.

PMID- 24932747
TI  - Combining radiographic and histological data for dental development to compare
      growth in the past and the present.
AB  - BACKGROUND: Being able to estimate the age at death of fossil hominins enables
      meaningful comparisons of both dental and general growth, past and present. AIM:
      The aim of this study was to use data for modern permanent canine formation
      derived from separate histological and radiographic studies to estimate the age
      at death of an early African Homo erectus specimen (KNM-WT 15 000) with a
      developing permanent maxillary canine. METHODS: Ground sections of 18 sexed
      modern human canines were used to reconstruct growth in tooth height along the
      enamel-dentine junction (EDJ) and onwards into root formation along the cement
      dentine junction (CDJ). Daily rates of enamel and dentine formation were used to
      put a time scale to cumulative fractions of tooth height. RESULTS: Age estimates
      for KNM-WT 15 000 averaged 7.89-8.8 years of age (range = 6.6-10.3 years) and
      were close to previous histological estimates for this individual (7.6-8.8
      years). CONCLUSIONS: Stages of dental development in KNM-WT 15 000 were easily
      accommodated within this age distribution of a modern sample. However, body mass
      and stature estimates for KNM-WT 15 000 fell well beyond those reported for a
      modern sample of 438 Sudanese children aged between 7.0-10 years.

PMID- 24932748
TI  - Isotopic and trace element evidence of dietary transitions in early life.
AB  - CONTEXT: Nursing behaviour has significant implications for individual health and
      population dynamics. Reconstruction of infant and early childhood diet has become
      a key focus in studies of past populations. OBJECTIVE: This paper reviews
      knowledge about how trace element and stable isotope composition of bone and
      dental tissues changes during development and how this may influence
      interpretation of biology and behaviour in past populations. METHODS: Studies of
      recent populations and osteological samples were reviewed. RESULTS: Four distinct
      stages of nutritional intake are recognized: gestation, exclusive breastfeeding,
      a transitional or weaning stage and fully weaned. The trace element and stable
      isotope composition of developing foetal and infant tissues differs during each
      of these stages due to differences in the source of nutrients and changes in
      metabolic parameters. CONCLUSION: Interpretation of early lifetime diet from
      trace element or stable isotope values requires a comprehensive and validated
      physiological model for changes during and at the transition between dietary
      stages. Micro-sampling of dental tissues offers the potential to reconstruct an
      individual record of early lifetime diet within a chronological framework and has
      several advantages over traditional cross-sectional techniques. Further research
      is necessary to understand the factors influencing intra-tooth variability in
      recovered signals and their chronological interpretation.

PMID- 24932749
TI  - Parturition lines in modern human wisdom tooth roots: do they exist, can they be
      characterized and are they useful for retrospective determination of age at first
      reproduction and/or inter-birth intervals?
AB  - BACKGROUND: Parturition lines have been described in the teeth of a number of
      animals, including primates, but never in modern humans. These accentuated lines
      in dentine are comprised of characteristic dark and light component zones. AIM:
      The aim of this study was to review the physiology underlying these lines and to
      ask if parturition lines exist in the third molar tooth roots of mothers known to
      have had one or more children during their teenage years. METHODS: Brief
      retrospective oral medical obstetric histories were taken from four mothers and
      compared with histological estimates for the timing of accentuated markings
      visible in longitudinal ground sections of their wisdom teeth. RESULTS: Evidence
      of accentuated markings in M3 root dentine matched the age of the mother at the
      time their first child was born reasonably well. However, the dates calculated
      for inter-birth intervals did not match well. CONCLUSIONS: Parturition lines
      corresponding to childbirth during the teenage years can exist in human M3 roots,
      but may not always do so. Without a written medical history it would not be
      possible to say with confidence that an accentuated line in M3 root dentine was
      caused by stress, illness or was a parturition line.

PMID- 24932750
TI  - Humans are not cooperative breeders but practice biocultural reproduction.
AB  - CONTEXT: Alloparental care and feeding of young is often called "cooperative
      breeding" and humans are increasingly described as being a cooperative breeding
      species. OBJECTIVE: To critically evaluate whether the human offspring care
      system is best grouped with that of other cooperative breeders. METHODS: (1)
      Review of the human system of offspring care in the light of definitions of
      cooperative, communal and social breeding; (2) re-analysis of human lifetime
      reproductive effort. RESULTS: Human reproduction and offspring care are distinct
      from other species because alloparental behaviour is defined culturally rather
      than by genetic kinship alone. This system allows local flexibility in
      provisioning strategies and ensures that care and resources often flow between
      unrelated individuals. This review proposes the term "biocultural reproduction"
      to describe this unique human reproductive system. In a re-analysis of human life
      history data, it is estimated that the intense alloparenting typical of human
      societies lowers the lifetime reproductive effort of individual women by 14-29%
      compared to expectations based upon other mammals. CONCLUSION: Humans are not
      cooperative breeders as classically defined; one effect of the unique strategy of
      human biocultural reproduction is a lowering of human lifetime reproductive
      effort, which could help explain lifespan extension.

PMID- 24932752
TI  - Eponyms in cardiothoracic radiology: part III--interstitium.
AB  - Eponyms serve the purpose of honoring individuals who have made important
      observations and discoveries. As with other fields of medicine, eponyms are
      frequently encountered in radiology, particularly in chest radiology. However,
      inappropriate use of an eponym may lead to potentially dangerous
      miscommunication. Moreover, an eponym may honor the incorrect person or a person
      who falls into disrepute. Despite their limitations, eponyms are still widespread
      in the medical literature. Furthermore, in some circumstances, more than one
      individual may have contributed to the description or discovery of a particular
      anatomical structure or disease, whereas in others, an eponym may have been
      incorrectly applied initially and propagated for years in the medical literature.
      Nevertheless, radiologic eponyms are a means of honoring those who have made
      lasting contributions to the field of radiology, and familiarity with these
      eponyms is critical for proper reporting and accurate communication. In addition,
      the acquisition of some historical knowledge about those whose names are
      associated with various structures or pathologic conditions conveys a sense of
      humanity in the science of medicine. In this third installment of this series,
      the authors discuss a number of chest radiology eponyms as they relate to the
      pulmonary interstitium, including relevant clinical and imaging features, as well
      biographical information of the respective eponym's namesake.

PMID- 24932751
TI  - TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival
      under beta-lactam antibiotic exposure.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant
      pathogen responsible for several difficult-to-treat infections in humans.
      Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent
      infections, are composed of mixed cell populations that contain organisms with
      low levels of resistance (hetero-resistant HeR) and those that display high
      levels of drug resistance (homo-resistant HoR). However, the full understanding
      of beta-lactam-mediated HeR/HoR selection remains to be completed. In previous
      studies we demonstrated that acquisition of the HoR phenotype during exposure to
      beta-lactam antibiotics depended on two key elements: (1) activation of the SOS
      response, a conserved regulatory network in bacteria that is induced in response
      to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic
      changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in
      order to increase the energy supply for cell-wall synthesis. In the present work,
      we identified that both main mechanistic components are associated through TCA
      cycle-mediated reactive oxygen species (ROS) production, which temporally affects
      DNA integrity and triggers activation of the SOS response resulting in enhanced
      mutagenesis. The present work brings new insights into a role of ROS generation
      on the development of resistance to beta-lactam antibiotics in a model of natural
      occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism. 

PMID- 24932753
TI  - Are numbers, size and brightness equally efficient in orienting visual attention?
      Evidence from an eye-tracking study.
AB  - A number of studies have shown strong relations between numbers and oriented
      spatial codes. For example, perceiving numbers causes spatial shifts of attention
      depending upon numbers' magnitude, in a way suggestive of a spatially oriented,
      mental representation of numbers. Here, we investigated whether this phenomenon
      extends to non-symbolic numbers, as well as to the processing of the continuous
      dimensions of size and brightness, exploring whether different quantitative
      dimensions are equally mapped onto space. After a numerical (symbolic Arabic
      digits or non-symbolic arrays of dots; Experiment 1) or a non-numerical cue
      (shapes of different size or brightness level; Experiment 2) was presented,
      participants' saccadic response to a target that could appear either on the left
      or the right side of the screen was registered using an automated eye-tracker
      system. Experiment 1 showed that, both in the case of Arabic digits and dot
      arrays, right targets were detected faster when preceded by large numbers, and
      left targets were detected faster when preceded by small numbers. Participants in
      Experiment 2 were faster at detecting right targets when cued by large-sized
      shapes and left targets when cued by small-sized shapes, whereas brightness cues
      did not modulate the detection of peripheral targets. These findings indicate
      that looking at a symbolic or a non-symbolic number induces attentional shifts to
      a peripheral region of space that is congruent with the numbers' relative
      position on a mental number line, and that a similar shift in visual attention is
      induced by looking at shapes of different size. More specifically, results
      suggest that, while the dimensions of number and size spontaneously map onto an
      oriented space, the dimension of brightness seems to be independent at a certain
      level of magnitude elaboration from the dimensions of spatial extent and number,
      indicating that not all continuous dimensions are equally mapped onto space. 

PMID- 24932754
TI  - A workplace violence educational program: a repeated measures study.
AB  - Violence against healthcare employees is a profound problem in the emergency
      department worldwide. One strategy to reduce the risk of violence is prevention
      focused education. The purpose of this paper was to report the learning outcomes
      of a workplace violence educational prevention program tailored to the needs of
      emergency department employees. A quasi-experimental design was used to determine
      the knowledge retention of program content following a hybrid (online and
      classroom) educational intervention. One hundred twenty emergency department
      employees that completed the workplace violence prevention program participated
      in the study. A repeated-measures analysis of variance was conducted to determine
      if individual test scores increased significantly between baseline, posttest, and
      six month posttest periods. The results indicated a significant time effect,
      Wilk's Lambda = .390, F (2, 118) = 26.554, p < .001, eta2 = .310. Follow-up
      polynomial contrasts indicated a significant linear effect with means increasing
      over time, F (1, 119) = 53.454, p < .001, eta2 = .310, while individual test
      scores became significantly higher over time. It was concluded that the use of a
      hybrid modality increases the probability that significant learning outcomes and
      retention will be achieved.

PMID- 24932755
TI  - Educational gradients in psychotropic medication use among older adults in Costa
      Rica and the United States.
AB  - OBJECTIVE: The relationship of education, psychiatric diagnoses, and use of
      psychotropic medication has been explored in the United States, but little is
      known about this relationship in poorer countries, despite the high burden of
      mental illness in these countries. This study estimated educational gradients in
      diagnosis and psychotropic drug use in the United States and Costa Rica, a middle
      income country with universal health insurance. METHODS: Analyses were conducted
      by using data of older adults (>=60) from the 2005 U.S. Medical Expenditure Panel
      Survey (N=4,788) and the 2005 Costa Rican Longevity and Healthy Aging Study
      (N=2,827). Logistic regressions examined the effect of education level (low,
      medium, or high) and urban residence on the rates of self-reported mental health
      diagnoses, screening diagnosis, and psychotropic medication use with and without
      an associated psychiatric diagnosis. RESULTS: Rates of self-reported diagnoses
      were lower in the United States (12%) than in Costa Rica (20%), possibly
      reflecting differences in survey wording. In both countries, the odds of having
      depression were significantly lower among persons with high education. In Costa
      Rica, use of psychotropic medication among persons with self-reported diagnoses
      increased by education level. CONCLUSIONS: The educational gradients in
      medication use were different in the United States and Costa Rica, and stigma and
      access to care in these countries may play an important role in these
      differences, although type of insurance did not affect educational gradients in
      the United States. These analyses increase the evidence of the role of education
      in use of the health care system.

PMID- 24932756
TI  - New generation of bioorthogonally applicable fluorogenic dyes with visible
      excitations and large Stokes shifts.
AB  - Synthesis of a set of new, azide bearing, biorthogonally applicable fluorogenic
      dyes with large Stokes shifts is presented herein. To assess the fluorogenic
      performance of these new dyes we have labeled a genetically modulated,
      cyclooctyne-bearing protein in lysate medium. Studies showed that the labels
      produce specific signal with minimal background fluorescence. We also provide
      theoretical insights into the design of such fluorogenic labels. 

PMID- 24932757
TI  - Melatonin secretion is impaired in women with preeclampsia and an abnormal
      circadian blood pressure rhythm.
AB  - Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia,
      accompanied by adverse outcomes. Melatonin plays pivotal role in biological
      circadian rhythms. This study investigated the relationship between melatonin
      secretion and circadian BP rhythm in preeclampsia. Cases were women with
      preeclampsia treated between January 2006 and June 2007 in the University
      Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological
      and gestational age, served as controls. Twenty-four hour ambulatory BP
      monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels
      were determined in day and night time samples by enzyme-linked immunoassays.
      Measurements were repeated 2 months after delivery. Thirty-one women with
      preeclampsia and 20 controls were included. Twenty-one of the 31 women with
      preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia
      there were significantly lower night time melatonin (48.4 +/- 24.7 vs. 85.4 +/-
      26.9 pg/mL, p<0.001) levels. Adjustment for circadian BP rhythm status ascribed
      this finding exclusively to non-dippers (p<0.01). Two months after delivery, in
      11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm
      reappeared. In contrast, in cases with retained non-dipping status (n=10)
      melatonin secretion rhythm remained impaired: daytime versus night time melatonin
      (33.5 +/- 13.0 vs. 28.0 +/- 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin
      levels were, overall, similar to serum melatonin. Circadian BP and melatonin
      secretion rhythm follow parallel course in preeclampsia, both during pregnancy
      and, at least 2 months after delivery. Our findings may be not sufficient to
      implicate a putative therapeutic effect of melatonin, however, they clearly
      emphasize that its involvement in the pathogenesis of a non-dipping BP in
      preeclampsia needs intensive further investigation.

PMID- 24932758
TI  - Fluorescent protein-expressing neural progenitor cells as a tool for
      transplantation studies.
AB  - The purpose of this study was to generate quadruple fluorescent protein (QFP)
      transgenic mice as a source for QFP-expressing neural stem and progenitor cells
      (NSCs/NPCs) that could be utilized as a tool for transplantation research. When
      undifferentiated, these NSCs only express cyan fluorescent protein (CFP);
      however, upon neuronal differentiation, the cells express yellow fluorescent
      protein (YFP). During astrocytic differentiation, the cells express green
      fluorescent protein (GFP), and during oligodendrocytic differentiation, the cells
      express red fluorescent protein (DsRed). Using immunocytochemistry,
      immunoblotting, flow cytometry and electrophysiology, quadruple transgenic NPCs
      (Q-NPCs) and GFP-sorted NPCs were comprehensively characterized in vitro.
      Overall, the various transgenes did not significantly affect proliferation and
      differentiation of transgenic NPCs in comparison to wild-type NPCs. In contrast
      to a strong CFP and GFP expression in vitro, NPCs did not express YFP and dsRed
      either during proliferation or after differentiation in vitro. GFP-positive
      sorted NPCs, expressing GFP under the control of the human GFAP promoter,
      demonstrated a significant improvement in astroglial differentiation in
      comparison to GFP-negative sorted NPCs. In contrast to non-sorted and GFP
      positive sorted NPCs, GFP-negative sorted NPCs demonstrated a high proportion of
      neuronal differentiation and proved to be functional in vitro. At 6 weeks after
      the intracerebroventricular transplantation of Q-NPCs into neonatal wild-type
      mice, CFP/DCX (doublecortin) double-positive transplanted cells were observed.
      The Q-NPCs did not express any other fluorescent proteins and did not mature into
      neuronal or glial cells. Although this model failed to visualize NPC
      differentiation in vivo, we determined that activation of the NPC glial
      fibrillary acid protein (GFAP) promoter, as indicated by GFP expression, can be
      used to separate neuronal and glial progenitors as a valuable tool for
      transplantation studies. 

PMID- 24932759
TI  - Ultrafine carbon black induces glutamate and ATP release by activating connexin
      and pannexin hemichannels in cultured astrocytes.
AB  - Ultrafine particles could enter central nervous system and were associated with
      brain damage. The underlying mechanisms have not been fully elucidated. Glutamate
      and ATP are important signaling molecules in brain physiology and pathology. We
      investigated whether ultrafine carbon black (ufCB) could regulate the release of
      glutamate and ATP from cultured cortical astrocytes and the involvement of
      hemichannels in the release mechanism. Our results showed that ufCB dose
      dependently increased glutamate and ATP release and activated hemichannels in
      astrocytes. ufCB-activated hemichannels were attributed to the activation of both
      connexin 43 (Cx43) and pannexin1 (Panx1) hemichannels, which was based on the
      finding of increased protein expression and distribution on cell surface of Cx43
      and Panx1, and the inhibiting effects of hemichannel inhibitor carbenoxolone,
      Cx43 hemichannel inhibitor (43)Gap27 and Panx1 hemichannel inhibitor (10)Panx1 on
      hemichannel activation. Furthermore, ufCB-induced glutamate and ATP release were
      dependent on Cx43 and Panx1 hemichannels, because carbenoxolone and (43)Gap27
      inhibited ufCB-induced glutamate and ATP release, and (10)Panx1 inhibited ufCB
      induced ATP release. Taken together, we demonstrated, for the first time, that
      ufCB could induce glutamate and ATP release by activating Cx43 and Panx1
      hemchannels in astrocytes. Our findings suggest a novel mechanism for
      neurotoxicity caused by ultrafine particles. 

PMID- 24932760
TI  - Photoelectrochemical DNA biosensors.

PMID- 24932761
TI  - Modified robotic-assisted thyroidectomy: an initial experience with the
      retroauricular approach.
AB  - OBJECTIVES/HYPOTHESIS: New approaches for robotic-assisted thyroidectomy,
      including the retroauricular approach, were recently described. We have modified
      the established surgical approach for retroauricular robotic thyroidectomy.
      Herein, we report our initial experience to identify challenges and limitations
      of this new surgical approach. STUDY DESIGN: Prospective case series. METHODS:
      This study was performed under institutional review board approval for patients
      who underwent retroauricular robotic hemithyroidectomy at an academic North
      American institution. The retroauricular approach was modified by using the space
      between the two heads of the sternocleidomastoid muscle as our working space.
      Additionally, selected patients underwent concomitant neck lift surgery with
      robotic thyroid surgery. Clinical characteristics, total operative time, blood
      loss, surgical outcomes, and length of hospital stay were evaluated. RESULTS:
      Twelve female patients were included in this study. Mean age was 45 +/- 4.43
      years, and mean body mass index was 28.6 +/- 2.15. Mean thyroid nodule size was
      1.15 +/- 0.26 cm(3). All cases were completed successfully via single
      retroauricular incision. There was no conversion to an open approach. Four out of
      12 patients (33%) underwent additional concomitant neck lift surgery, with a mean
      total operative time of 156 +/- 15.88 minutes. The mean operative time for the
      remaining eight patients who underwent the robotic approach without additional
      neck lift surgery was 145.4 +/- 10.08 minutes. There were no cases of permanent
      vocal cord paralysis or permanent hypoparathyroidism. Mean blood loss was 22.4 +/
      4.32 mL. Four patients (33%) were discharged home on the same day of surgery,
      and the remaining eight patients were discharged after an overnight stay.
      CONCLUSIONS: Single-incision retroauricular robotic hemithyroidectomy can be a
      safe and feasible alternative to other remote access techniques. Neck lift
      surgery can be performed safely in a select group of patients. However, future
      studies are warranted to further evaluate the benefits and limitations of this
      novel approach.

PMID- 24932763
TI  - Personality * hormone interactions in adolescent externalizing psychopathology.
AB  - The "dual-hormone" hypothesis predicts that testosterone and cortisol will
      jointly regulate aggressive and socially dominant behavior in children and adults
      (e.g., Mehta & Josephs, 2010). The present study extends research on the dual
      hormone hypothesis by testing the interaction between testosterone, cortisol, and
      personality disorder (PD) traits in predicting externalizing problems in a
      community sample of adolescent males and females. Participants were 106 youth
      from the community, ranging in age from 13-18 (Mage = 16.01 years, SDage = 1.29),
      and their parents. Parents and youth provided ratings on an omnibus measure of
      personality pathology and externalizing problems. Youth provided saliva samples
      via passive drool from which testosterone and cortisol levels were obtained.
      Robust moderation of the joint effects of testosterone and cortisol on parent
      reported externalizing problems was found for both higher-order PD traits
      associated with externalizing psychopathology (Disagreeableness and Emotional
      Instability). Higher testosterone was associated with externalizing outcomes, but
      only when cortisol was low, and only among youth with high levels of
      Disagreeableness and Emotional Instability. These findings provide the first
      evidence for the dual-hormone hypothesis in a mixed-sex sample of community
      adolescents, but importantly offer novel evidence for the importance of
      personality traits. Examination of the joint regulation of externalizing problems
      by testosterone and cortisol in the context of adolescent personality may help to
      clarify inconsistent main effects of testosterone and cortisol on clinical
      externalizing phenotypes.

PMID- 24932762
TI  - Psychopathic and externalizing offenders display dissociable dysfunctions when
      responding to facial affect.
AB  - Despite similarity in their disinhibited behaviors, the cognitive-affective
      mechanisms that characterize psychopathy and externalizing are relatively
      distinct. One theoretical perspective suggests that psychopathy is associated
      with an early attention bottleneck that precludes the processing of contextual
      information, leading to a rigid goal-directed focus. Alternatively, externalizing
      may be associated with an overallocation of processing resources to
      motivationally salient information, which disrupts the use of cognitive control.
      In this study, male prisoners assessed on psychopathic and externalizing traits
      performed a new gaze detection task involving affective faces. As predicted,
      psychopathy but not externalizing was associated with superior performance on the
      gaze-detection task when the necessity of using contextual affect to regulate
      goal-directed behavior was minimized. Conversely, externalizing but not
      psychopathy was associated with increased errors on trials that required
      participants to use affective expressions, specifically fear, as a cue to inhibit
      dominant responses. These results have theoretical and applied significance for
      both psychopathic and externalizing forms of disinhibition. Recognition and
      utilization of facial affect are important for socialization and interpersonal
      interactions; therefore, any cognitive-affective processes that interrupt the
      fluency with which this information is processed may be important for
      understanding the underpinnings of disinhibition.

PMID- 24932764
TI  - Psychopathy, DSM-5, and a caution.
AB  - Recently developed models of psychopathy include such traits as fearlessness,
      boldness, and invulnerability. Section III of Diagnostic and Statistical Manual
      of Mental Disorders (DSM-5) includes as well a psychopathy specifier that is
      modeled after these traits. The purpose of the current study was to test
      empirically the convergent and discriminant validity of the Psychopathic
      Personality Inventory-Revised (PPI-R), the Triarchic Psychopathy Measure (TriPM),
      the Elemental Psychopathy Assessment (EPA), and the Personality Inventory for DSM
      5 (PID-5) with respect to their relationship to one another, with traditional
      measures of psychopathy and antisocial personality disorder, and with a measure
      of the 5-factor model. Participants were 2 samples of community adults (280 and
      196) who indicated that they have engaged in criminal activities. The results
      indicated good convergent and discriminant validity for the PPI-R, TriPM, EPA,
      and the PID-5 psychopathy specifiers, as well as relationships with a measure of
      the 5 factor model that were quite distinct from the relationships obtained for
      traditional measures of antisocial personality disorder and psychopathy. However,
      concerns are raised with respect to a reliance on reverse-coded items for the
      assessment of components of psychopathy.

PMID- 24932767
TI  - Boston keratoprosthesis type 1 for herpes simplex and herpes zoster keratopathy.
AB  - PURPOSE: The aim of this study was to evaluate and compare the outcomes of Boston
      keratoprosthesis type 1 (Kpro-1) in eyes with herpes simplex virus (HSV) and
      herpes zoster virus (HZV) keratopathy. METHODS: A retrospective review was
      performed of the medical records of every patient treated with a Boston Kpro-1 at
      the University of Iowa Hospitals and Clinics between January 1, 2008 and July 1,
      2012. Eyes with visual loss due to HSV or HZV keratopathy were included in the
      statistical analysis. The main outcome measures were graft retention,
      postoperative complications, and visual outcome. RESULTS: Nine eyes met the
      inclusion criteria, including 5 eyes in the HSV group and 4 eyes in the HZV
      group. The graft retention rate was 100% in the HSV group after a mean follow-up
      of 48.4 months, compared with 25% in the HZV group after 50.5 months (P = 0.048).
      There were 3 cases of microbial keratitis, including 2 eyes that also developed
      endophthalmitis, in the HZV group, compared with no cases in the HSV group (P =
      0.048). There was significantly better best-corrected visual acuity at the most
      recent examination in the HSV group than in the HZV group (P = 0.019). All 5 HSV
      eyes had improved best-corrected visual acuity compared with preoperative acuity,
      whereas only 1 HZV eye experienced a similar result (P = 0.048). CONCLUSIONS:
      Kpro-1 is associated with an excellent prognosis for graft retention, acceptably
      low prevalence of sight-threatening complications, and highly satisfactory visual
      improvement in eyes with HSV keratopathy, but not in eyes with HZV keratopathy.

PMID- 24932765
TI  - Effects of intravenous dexmedetomidine on emergence agitation in children under
      sevoflurane anesthesia: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Emergence agitation (EA) is a common complication in children under
      sevoflurane anesthesia. The aim of this meta-analysis was to evaluate the effects
      of intravenous dexmedetomidine on EA in children under sevoflurane anesthesia.
      METHODS: A comprehensive literature search was conducted to identify clinical
      trials that evaluated the effects of intravenous dexmedetomidine and placebo on
      EA in children under sevoflurane anesthesia. The search collected trials from
      MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and
      Web of Science. Analysis was conducted using STATA version 12.0. Data from each
      trial were pooled using relative ratio (RR) for dichotomous data or weighted mean
      difference (WMD) for continuous data and corresponding 95% confidence interval
      (95% CI). Heterogeneity assessment, sensitivity analysis, and publication bias
      were performed. RESULTS: Twelve trials, in which 459 patients received
      dexmedetomidine and 353 patients received placebo, were included in this
      analysis. We found that intravenous dexmedetomidine decreased the incidences of
      EA (RR = 0.346, 95% CI 0.263 to 0.453, P<0.001), and postoperative pain (RR =
      0.405, 95% CI 0.253 to 0.649, P<0.001). Intravenous dexmedetomidine also
      prolonged extubation time (WMD = 0.617, 95% CI 0.276 to 958, P<0.001), and
      emergence time (WMD = 0.997, 95% CI 0.392 to 1.561, P = 0.001). Further evidences
      are required to evaluate the incidence of postoperative nausea and vomiting
      (PONV). Sensitivity analysis strengthened evidences for lower incidences of EA,
      pain, and prolonged extubation time, and emergence time. Funnel plots did not
      detect any significant publication bias. CONCLUSION: Meta-analysis demonstrated
      that dexmedetomidine decreased the incidence of EA in children under sevoflurane
      anesthesia.

PMID- 24932768
TI  - Scalable production of microbially mediated zinc sulfide nanoparticles and
      application to functional thin films.
AB  - A series of semiconducting zinc sulfide (ZnS) nanoparticles were scalably,
      reproducibly, controllably and economically synthesized with anaerobic metal
      reducing Thermoanaerobacter species. These bacteria reduced partially oxidized
      sulfur sources to sulfides that extracellularly and thermodynamically
      incorporated with zinc ions to produce sparingly soluble ZnS nanoparticles with
      ~5nm crystallites at yields of ~5gl(-1)month(-1). A predominant sphalerite
      formation was facilitated by rapid precipitation kinetics, a low cation/anion
      ratio and a higher zinc concentration compared to background to produce a
      naturally occurring hexagonal form at the low temperature, and/or water
      adsorption in aqueous conditions. The sphalerite ZnS nanoparticles exhibited
      narrow size distribution, high emission intensity and few native defects. Scale
      up and emission tunability using copper doping were confirmed spectroscopically.
      Surface characterization was determined using Fourier transform infrared and X
      ray photoelectron spectroscopies, which confirmed amino acid as proteins and
      bacterial fermentation end products not only maintaining a nano-dimensional
      average crystallite size, but also increasing aggregation. The application of ZnS
      nanoparticle ink to a functional thin film was successfully tested for potential
      future applications. 

PMID- 24932769
TI  - Bone and metal: an orthopaedic perspective on osseointegration of metals.
AB  - The area of implant osseointegration is of major importance, given the predicted
      significant rise in the number of orthopaedic procedures and an increasingly
      ageing population. Osseointegration is a complex process involving a number of
      distinct mechanisms affected by the implant bulk properties and surface
      characteristics. Our understanding and ability to modify these mechanisms through
      alterations in implant design is continuously expanding. The following review
      considers the main aspects of material and surface alterations in metal implants,
      and the extent of their subsequent influence on osseointegration. Clinically,
      osseointegration results in asymptomatic stable durable fixation of orthopaedic
      implants. The complexity of achieving this outcome through incorporation and
      balance of contributory factors is highlighted through a clinical case report. 

PMID- 24932770
TI  - Biomineralization special issue.

PMID- 24932771
TI  - Tuning the architecture of three-dimensional collagen hydrogels by physiological
      macromolecular crowding.
AB  - Macromolecular crowding is an optimal physiological feature in intracellular and
      extracellular spaces, and results from a variety of macromolecules occupying
      space and contributing to a fractional volume occupancy. Here, we show that soft
      collagen hydrogels assembled in nature-inspired crowded conditions feature
      enhanced biophysical properties. We demonstrate that crowding tunes the rate of
      collagen nucleation and fiber growth, affecting fiber diameter and organization.
      Adjustments of crowding levels during collagen assembly tune the gel pore size,
      protein permeability, transparency and resistance to enzymatic degradation.
      Furthermore, gels assembled in crowded conditions are twice as resistant to
      mechanical stress as the controls, inducing a 70% boost of proliferation of stem
      cells cultured on tuned hydrogels. Emulating the crowdedness of interstitial
      fluids therefore represents a way to optimize the properties of soft collagen
      gels, with promising applications in soft biomaterials design. 

PMID- 24932772
TI  - Highly enantioselective synthesis of chiral cyclic allylic amines via Rh
      catalyzed asymmetric hydrogenation.
AB  - Highly regioselective and enantioselective asymmetric hydrogenation of cyclic
      dienamides catalyzed by an Rh-DuanPhos complex has been developed, which provides
      a readily accessible method for the synthesis of chiral cyclic allylic amines in
      excellent enantioselectivities (up to 99% ee). The products are valuable chiral
      building blocks and could be easily transformed to multisubstituted cyclohexane
      derivatives. 

PMID- 24932773
TI  - Modified montmorillonite clay microparticles for stable oil-in-seawater
      emulsions.
AB  - Environmentally benign clay particles are of great interest for the stabilization
      of Pickering emulsions. Dodecane-in-synthetic seawater (SSW) emulsions formed
      with montmorillonite (MMT) clay microparticles modified with bis(2
      hydroxyethyl)oleylamine were stable against coalescence, even at clay
      concentrations down to 0.1% w/v. Remarkably, as little as 0.001% w/v surfactant
      lowered the hydrophilicity of the clay to a sufficient level for stabilization of
      oil-in-SSW emulsions. The favorable effect of SSW on droplet size reduction and
      emulsion stability enhancement is hypothesized to be due to reduced electrostatic
      repulsion between adsorbed clay particles and a consequent increase in the
      continuous phase (an aqueous clay suspension) viscosity. Water/oil (W/O)
      emulsions were inverted to O/W either by decreasing the mass ratio of surfactant
      to-clay (transitional inversion) or by increasing the water volume fraction
      (catastrophic inversion). For both types of emulsions, coalescence was minimal
      and the sedimentation or creaming was highly correlated with the droplet size.
      For catastrophic inversions, the droplet size of the emulsions was smaller in the
      case of the preferred curvature. Suspensions of concentrated clay in oil
      dispersions in the presence of surfactant were stable against settling. The mass
      transfer pathways during emulsification of oil containing the clay particles were
      analyzed on the droplet size/stability phase diagrams to provide insight for the
      design of dispersant systems for remediating surface and subsurface oceanic oil
      spills. 

PMID- 24932775
TI  - Diffusion models: still promoting progresses. Comments on "Multiscale approach to
      pest insect monitoring: random walks, pattern formation, synchronization and
      networks" by S. Petrovskii, N. Petrovskaya and D. Bearup.

PMID- 24932774
TI  - Geographic variability in the association between socioeconomic status and BMI in
      the USA and Canada.
AB  - OBJECTIVE: Reported associations between socioeconomic status (SES) and obesity
      are inconsistent depending on gender and geographic location. Globally, these
      inconsistent observations may hide a variation in the contextual effect on
      individuals' risk of obesity for subgroups of the population. This study explored
      the regional variability in the association between SES and BMI in the USA and in
      Canada, and describes the geographical variance patterns by SES category.
      METHODS: The 2009-2010 samples of the Behavioral Risk Factor Surveillance System
      (BRFSS) and the Canadian Community Health Survey (CCHS) were used for this
      comparison study. Three-level random intercept and differential variance
      multilevel models were built separately for women and men to assess region
      specific BMI by SES category and their variance bounds. RESULTS: Associations
      between individual SES and BMI differed importantly by gender and countries. At
      the regional-level, the mean BMI variation was significantly different between
      SES categories in the USA, but not in Canada. In the USA, whereas the county
      specific mean BMI of higher SES individuals remained close to the mean, its
      variation grown as SES decreased. At the county level, variation of mean BMI
      around the regional mean was 5 kg/m2 in the high SES group, and reached 8.8 kg/m2
      in the low SES group. CONCLUSIONS: This study underlines how BMI varies by
      country, region, gender and SES. Lower socioeconomic groups within some regions
      show a much higher variation in BMI than in other regions. Above the BMI regional
      mean, important variation patterns of BMI by SES and place of residence were
      found in the USA. No such pattern was found in Canada. This study suggests that a
      change in the mean does not necessarily reflect the change in the variance.
      Analyzing the variance by SES may be a good way to detect subtle influences of
      social forces underlying social inequalities.

PMID- 24932776
TI  - Emodin opposes chronic unpredictable mild stress induced depressive-like behavior
      in mice by upregulating the levels of hippocampal glucocorticoid receptor and
      brain-derived neurotrophic factor.
AB  - Emodin, the major active component of Rhubarb, has shown neuroprotective
      activity. This study is attempted to investigate whether emodin possesses
      beneficial effects on chronic unpredictable mild stress (CUMS)-induced behavioral
      deficits (depression-like behaviors) and explore the possible mechanisms. ICR
      mice were subjected to chronic unpredictable mild stress for 42 consecutive days.
      Then, emodin and fluoxetine (positive control drug) were administered for 21
      consecutive days at the last three weeks of CUMS procedure. The classical
      behavioral tests: open field test (OFT), sucrose preference test (SPT), tail
      suspension test (TST) and forced swimming test (FST) were applied to evaluate the
      antidepressant effects of emodin. Then plasma corticosterone concentration,
      hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor
      (BDNF) levels were tested to probe the mechanisms. Our results indicated that 6
      weeks of CUMS exposure induced significant depression-like behavior, with high,
      plasma corticosterone concentration and low hippocampal GR and BDNF expression
      levels. Whereas, chronic emodin (20, 40 and 80 mg/kg) treatments reversed the
      behavioral deficiency induced by CUMS exposure. Treatment with emodin normalized
      the change of plasma corticosterone level, which demonstrated that emodin could
      partially restore CUMS-induced HPA axis impairments. Besides, hippocampal GR
      (mRNA and protein) and BDNF (mRNA) expressions were also up-regulated after
      emodin treatments. In conclusion, emodin remarkably improved depression-like
      behavior in CUMS mice and its antidepressant activity is mediated, at least in
      part, by the up-regulating GR and BDNF levels in hippocampus.

PMID- 24932777
TI  - Lignan formation in hairy root cultures of Edelweiss (Leontopodium nivale ssp.
      alpinum (Cass.) Greuter).
AB  - A hairy root line of Edelweiss (Leontopodium nivale ssp. alpinum (Cass.) Greuter)
      was obtained upon transformation with Agrobacterium rhizogenes strain ATCC15834.
      Elicitation of this line with silver nitrate, sucrose, methyl jasmonate and yeast
      extract at various concentrations in most cases resulted in a stimulation of
      lignan biosynthesis. Through elicitation with 6% sucrose the roots accumulated
      the pharmacologically active lignans leoligin and 5-methoxy-leoligin at levels of
      0.0678% and 0.0372%, respectively, without significant growth inhibition. These
      lignan levels were comparable to those found in intact roots of cultivated
      Edelweiss. The biotechnological production of leoligin could be an attractive
      option for the continuous, field culture-independent production of the valuable
      secondary metabolites leoligin and 5-methoxy-leoligin. 

PMID- 24932778
TI  - Part 2: Sensitivity comparisons of the mayfly Centroptilum triangulifer to
      Ceriodaphnia dubia and Daphnia magna using standard reference toxicants; NaCl,
      KCl and CuSO4.
AB  - Criteria for establishing water quality standards that are protective for 95% of
      the native species are generally based upon laboratory toxicity tests. These
      tests utilize common model organisms that have established test methods. However,
      for invertebrates these species represent mostly the zooplankton community and
      are not inclusive of all taxa. In order to examine a potential under
      representation in emerging aquatic invertebrates the US Environmental Protection
      Agency has cultured a parthenogenetic mayfly, Centroptilum triangulifer
      (Ephemeroptera: Baetidae). This study established a 48h acute and a 14-day short
      term chronic testing procedure for C. triangulifer and compared its sensitivity
      to two model invertebrates, Ceriodaphnia dubia and Daphnia magna. Toxicity tests
      were conducted to determine mortality and growth effects using standard reference
      toxicants: NaCl, KCl and CuSO4. In 48-h acute tests, the average LC50 for the
      mayfly was 659mgL(-1) NaCl, 1957mgL(-1) KCl, and 11MUgL(-1) CuSO4. IC25 values,
      using dry weight as the endpoint, were 228mgL(-1) NaCl, 356mgL(-1) KCl and 5MUgL(
      1) CuSO4. C. triangulifer was the most sensitive species in NaCl acute and
      chronic growth tests. At KCl concentrations tested, C. triangulifer was less
      sensitive for acute tests but was equally or more sensitive than C. dubia and D.
      magna for growth measurements. This study determined C. triangulifer has great
      potential and benefits for use in ecotoxicological studies.

PMID- 24932779
TI  - Heuristic modeling of carcinogenesis for the population with dichotomous
      susceptibility to cancer: a pancreatic cancer example.
AB  - At present, carcinogenic models imply that all individuals in a population are
      susceptible to cancer. These models either ignore a fall of the cancer incidence
      rate at old ages, or use some poorly identifiable parameters for its accounting.
      In this work, a new heuristic model is proposed. The model assumes that, in a
      population, only a small fraction (pool) of individuals is susceptible to cancer
      and decomposes the problem of the carcinogenic modeling on two sequentially
      solvable problems: (i) determination of the age-specific hazard rate in
      individuals susceptible to cancer (individual hazard rate) from the observed
      hazard rate in the population (population hazard rate); and (ii) modelling of the
      individual hazard rate by a chosen "up" of the theoretical hazard function
      describing cancer occurrence in individuals in time (age). The model considers
      carcinogenesis as a failure of individuals susceptible to cancer to resist cancer
      occurrence in aging and uses, as the theoretical hazard function, the three
      parameter Weibull hazard function, often utilized in a failure analysis. The
      parameters of this function, providing the best fit of the modeled and observed
      individual hazard rates (determined from the population hazard rates), are the
      outcomes of the modeling. The model was applied to the pancreatic cancer data. It
      was shown that, in the populations stratified by gender, race and the geographic
      area of living, the modeled and observed population hazard rates of pancreatic
      cancer occurrence have similar turnovers at old ages. The sizes of the pools of
      individuals susceptible to this cancer: (i) depend on gender, race and the
      geographic area of living; (ii) proportionally influence the corresponding
      population hazard rates; and (iii) do not influence the individual hazard rates.
      The model should be further tested using data on other types of cancer and for
      the populations stratified by different categorical variables. 

PMID- 24932780
TI  - Event-related potentials for post-error and post-conflict slowing.
AB  - In a reaction time task, people typically slow down following an error or
      conflict, each called post-error slowing (PES) and post-conflict slowing (PCS).
      Despite many studies of the cognitive mechanisms, the neural responses of PES and
      PCS continue to be debated. In this study, we combined high-density array EEG and
      a stop-signal task to examine event-related potentials of PES and PCS in sixteen
      young adult participants. The results showed that the amplitude of N2 is greater
      during PES but not PCS. In contrast, the peak latency of N2 is longer for PCS but
      not PES. Furthermore, error-positivity (Pe) but not error-related negativity
      (ERN) was greater in the stop error trials preceding PES than non-PES trials,
      suggesting that PES is related to participants' awareness of the error. Together,
      these findings extend earlier work of cognitive control by specifying the neural
      correlates of PES and PCS in the stop signal task. 

PMID- 24932781
TI  - Poly(ADP-ribose) polymerase inhibition improves endothelin-1-induced endothelial
      dysfunction in rat thoracic aorta.
AB  - AIM: The aim of this study was to investigate whether poly(ADP-ribose) polymerase
      (PARP) inhibition improves endothelin-1 (ET-1)-induced endothelial dysfunction
      (ED). METHODS: Isolated rat thoracic aorta rings were incubated with ET-1 (10
      nmol/L) in the presence or absence of either polyethylene glycol-superoxide
      dismutase (PEG-SOD; a cell-permeable superoxide radical scavenger, 41 U/mL) plus
      apocynin (a NADPH oxidase inhibitor, 300 umol/L) or PJ34 (an inhibitor of polyADP
      ribose polymerase, 3 umol/L) for 18 h. Isometric tension studies were performed
      in response to acetylcholine (ACh; an endothelium-dependent vasodilator), sodium
      nitroprusside (SNP; an endothelium-independent vasodilator), and phenylephrine
      (Phe). PARP-1 and PAR (an end-product of PARP activity) expressions were
      evaluated by both Western blot and immunohistochemistry. RESULTS: Incubation of
      thoracic aorta rings with ET-1 resulted in a significant inhibition of the
      response to ACh, while SNP-induced relaxation was unaffected. The contractile
      response to Phe increased in arteries that were incubated with ET-1. PARP-1 and
      PAR expressions increased after ET-1 incubation. The diminished vasoreactivity as
      well as changes in expressions of PARP-1 and PAR in ET-1-incubated vessels were
      improved by both PEG-SOD plus apocynin and PJ34. CONCLUSION: Our studies
      demonstrate that ED induced by ET-1 seems to be effected via oxidative stress in
      the thoracic aorta endothelium with subsequent activation of the PARP pathway.

PMID- 24932782
TI  - Genetic risk score and adiposity interact to influence triglyceride levels in a
      cohort of Filipino women.
AB  - BACKGROUND/OBJECTIVES: Individually, genetic variants only moderately influence
      cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this
      study we generated genetic risk scores from a combination of previously reported
      variants influencing CM traits, and used these scores to explore how adiposity
      levels could mediate genetic contributions to CM traits. SUBJECTS/METHODS:
      Participants included 1649 women from the 2005 Cebu Longitudinal Health and
      Nutrition Survey. Three genetic risk scores were constructed for C-reactive
      protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides
      (TGs). We used linear regression models to assess the association between each
      genetic risk score and its related trait. We also tested for interactions between
      each score and measures of adiposity. RESULTS: Each genetic risk score explained
      a greater proportion of variance in trait levels than any individual genetic
      variant. We found an interaction between the TG genetic risk score (2.29-14.34
      risk alleles) and waist circumference (WC) (Pinteraction=1.66 * 10(-2)). Based on
      model predictions, for individuals with a higher TG genetic risk score (75th
      percentile=12), having an elevated WC (?80 cm) increased TG levels from 1.32 to
      1.71 mmol l(-1). However, for individuals with a lower score (25th percentile=7),
      having an elevated WC did not significantly change TG levels. CONCLUSIONS: The TG
      genetic risk score interacted with adiposity to synergistically influence TG
      levels. For individuals with a genetic predisposition to elevated TG levels, our
      results suggest that reducing adiposity could possibly prevent further increases
      in TG levels and thereby lessen the likelihood of adverse health outcomes such as
      cardiovascular disease.

PMID- 24932783
TI  - Preoperative angiotensin axis blockade therapy, intraoperative hypotension, and
      the risks of postoperative acute kidney injury.

PMID- 24932784
TI  - What do patients consider to be the most important outcomes for effectiveness
      studies on migraine treatment? Results of a Delphi study.
AB  - BACKGROUND: The outcome measures most frequently used in studies on the
      effectiveness of migraine treatment are whether the patient is free of pain,
      nausea, and free of photophobia/phonophobia within two hours. However, no patient
      centred outcome measures are available. Therefore, we performed an online Delphi
      procedure to compile a list of outcome measures deemed most important to migraine
      patients. METHODS: From a large database of migraine patients, we randomly
      selected 150 males and 150 females patients. We asked the open-ended question:
      'If a new medicine was developed for migraine attacks, what would you wish the
      effect of this medication to be?' In the second and third rounds, we presented
      the answers of the first round and asked the patients to rate the importance of
      each item. RESULTS: The initial response rate was 56% (n = 169). In the
      subsequent rounds the response rates were 90% (n = 152), and 97% (n = 147),
      respectively. Patients wanted their attack medication to treat the headache
      within 30 min, to prevent the attack from getting worse, to ensure they could
      function properly within 1 h, and prevent the recurrence of symptoms during the
      same day. CONCLUSIONS: The currently used outcome measures in migraine research
      do not sufficiently reflect the wishes of patients. Patients want the medication
      to work faster, to take away pain at an earlier stage, to make them able to
      function properly quickly, and to prevent recurrence. These aspects should be
      considered in future evaluation of new attack medication for migraine.

PMID- 24932785
TI  - Global emission inventories for C4-C14 perfluoroalkyl carboxylic acid (PFCA)
      homologues from 1951 to 2030, Part I: production and emissions from quantifiable
      sources.
AB  - We quantify global emissions of C4-C14 perfluoroalkyl carboxylic acid (PFCA)
      homologues during the life-cycle of products based on perfluorooctanoic acid
      (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonyl fluoride (POSF),
      and fluorotelomer compounds. We estimate emissions of 2610-21400 tonnes of C4-C14
      PFCAs in the period from 1951 to 2015, and project 20-6420 tonnes to be emitted
      from 2016 to 2030. The global annual emissions steadily increased in the period
      1951-2002, followed by a decrease and then another increase in the period 2002
      2012. Releases from fluoropolymer production contributed most to historical PFCA
      emissions (e.g. 55-83% in 1951-2002). Since 2002, there has been a geographical
      shift of industrial sources (particularly fluoropolymer production sites) from
      North America, Europe and Japan to emerging Asian economies, especially China.
      Sources differ between PFCA homologues, sometimes considerably, and the relative
      contributions of each source change over time. For example, whereas 98-100% of
      historical (1951-2002) PFOA emissions are attributed to direct releases during
      the life-cycle of products containing PFOA as ingredients or impurities, a much
      higher historical contribution from PFCA precursor degradation is estimated for
      some other homologues (e.g. 9-78% for PFDA). We address the uncertainties of the
      PFCA emissions by defining a lower and a higher emission scenario, which differ
      by approximately a factor of eight. 

PMID- 24932786
TI  - Role of nurse practitioners in encouraging use of personal health records.
AB  - With increased mobility, it is important that individuals keep their own personal
      health records (PHRs). Nurse practitioners are encouraged to assume greater
      responsibility for PHR adoption and recognize the key role they play in
      recommending PHR use. This article also briefly discusses college students'
      perceptions of their exposure to online PHRs.

PMID- 24932787
TI  - Beyond the exam room.

PMID- 24932788
TI  - Dimethyl fumarate (Tecfidera) for multiple sclerosis.

PMID- 24932789
TI  - Alpha-1 antitrypsin deficiency.

PMID- 24932790
TI  - Federal Trade Commission policy paper promotes unrestricted practice.

PMID- 24932793
TI  - Late-onset postpartum preeclampsia: a case study.
AB  - Late-onset postpartum preeclampsia is atypical and potentially life-threatening.
      Diagnosis is frequently delayed because signs and symptoms of significant disease
      are subtle, thus, nurse practitioners should have a high index of suspicion.
      Immediate consultation, diagnosis, initial management, pathophysiology, and
      breastfeeding support are discussed as well as patient education and future
      health implications.

PMID- 24932794
TI  - Reducing the burden of medication costs to improve medication adherence.
AB  - The high cost of medications is one reason that patients do not adhere to
      treatment plans. Providers can take actions to relieve the economic burden such
      as prescribing generic medications and offering patients information on various
      resources, including discount generic drug lists, discount cards, mail-order
      pharmacies, and prescription assistance programs.

PMID- 24932795
TI  - A snapshot of the latest heart failure guidelines.
AB  - Heart failure (HF) is a complex chronic condition with high morbidity and
      mortality. The purpose of this article is to present a snapshot of the 2013
      ACCF/AHA guidelines focusing on management and treatment of HF in primary care.

PMID- 24932797
TI  - Effect of stress echocardiography testing on changes in cardiovascular risk
      behaviors in postmenopausal women: a prospective survey study.
AB  - BACKGROUND: We evaluated the impact of contrast stress echocardiography (CSE)
      testing results on cardiovascular (CV) risk behaviors in postmenopausal women
      presenting with chest pain symptoms. This was a substudy of the Stress
      Echocardiography in Menopausal Women at Risk for Coronary Artery Disease (SMART)
      trial. METHODS: From 2004 to 2007, 366 women (mean age 54.4 +/- 5.5 years, range
      40-65; body mass index (BMI) 31.4 +/- 6.68; Caucasian in 95%) completed CSE and
      were invited to participate in the Women's Heart Clinic Risk Assessment
      Questionnaire (WHCRAQ survey) at the time of CSE and after 2 years. Of the 366,
      203 (55%) postmenopausal women completed both the baseline and 2-year follow-up
      surveys (age 61 +/- 5 years; Framingham risk score 6 +/- 4%, 81% treadmill CSE,
      19% dobutamine CSE). WHCRAQ assessed medical history, hormone therapy (HT), and
      CV risk behaviors (cigarette smoking history, including current smoking and mean
      cigarettes smoked per day; physical activity or exercise, including mean exercise
      minutes per week; and dietary fat intake, alcohol intake, and mean alcohol drinks
      per week). Abnormal CSE was defined as a new or worsening stress wall motion
      abnormality. Post-CSE changes in CV risk behaviors were determined by comparing
      baseline versus 2-year data. RESULTS: Of the 203 women who completed the survey
      at baseline and 2-year CSE, 29 were excluded to avoid confounding effect
      (coronary angiography [CA] was performed during follow-up). Of 174 women (55%
      hypertensive, 10% diabetic, 76% hyperlipidemic, and 25% on HT), CSE was abnormal
      in 10%. Baseline characteristics were not significantly different in normal
      versus abnormal CSE, apart from diabetes (8% vs. 24%, p=0.04). Slightly more
      women with normal CSE were taking HT than not (27% vs. 12%, p=0.19). CV risk
      behaviors that were different in normal versus abnormal CSE included current
      smoking, alcohol drinks per week, and higher fat diet (8% vs. 24%, p=0.03; 2.5 +/
      3.5 vs. 1.94+/-5.2, p=0.031; and 92% vs. 76%, p=0.03, respectively). Cigarette
      smoking decreased (mean difference of -1.5 cigarettes per day, p=0.014) in the
      abnormal-CSE group, whereas number of alcohol drinks per week increased (mean
      difference +0.38, p=0.009) in the normal-CSE group. CONCLUSION: We observed an
      association of lifestyle changes with CSE test results in postmenopausal women.

PMID- 24932799
TI  - Evaluation of genotoxicity testing of FDA approved large molecule therapeutics.
AB  - Large molecule therapeutics (MW>1000daltons) are not expected to enter the cell
      and thus have reduced potential to interact directly with DNA or related
      physiological processes. Genotoxicity studies are therefore not relevant and
      typically not required for large molecule therapeutic candidates. Regulatory
      guidance supports this approach; however there are examples of marketed large
      molecule therapeutics where sponsors have conducted genotoxicity studies. A
      retrospective analysis was performed on genotoxicity studies of United States FDA
      approved large molecule therapeutics since 1998 identified through the Drugs@FDA
      website. This information was used to provide a data-driven rationale for
      genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99
      therapeutics identified were tested for genotoxic potential. None of the
      therapeutics tested showed a positive outcome in any study except the peptide
      glucagon (GlucaGen(r)) showing equivocal in vitro results, as stated in the
      product labeling. Scientific rationale and data from this review indicate that
      testing of a majority of large molecule modalities do not add value to risk
      assessment and support current regulatory guidance. Similarly, the data do not
      support testing of peptides containing only natural amino acids. Peptides
      containing non-natural amino acids and small molecules in conjugated products may
      need to be tested. 

PMID- 24932798
TI  - Chronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of
      GluA1-subunit deficient mice.
AB  - Abnormal excitatory glutamate neurotransmission and plasticity have been
      implicated in schizophrenia and affective disorders. Gria1-/- mice lacking GluA1
      subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust
      novelty-induced hyperactivity, social deficits and heightened approach features,
      suggesting that they could be used to test for anti-manic activity of drugs.
      Here, we tested the efficacy of chronic treatment with established anti-manic
      drugs on behavioural properties of the Gria1-/- mice. The mice received standard
      mood stabilizers (lithium and valproate) and novel ones (topiramate and
      lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at
      least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of
      the Gria1-/- mice, especially by promoting the habituation, while none of them
      attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet.
      Treatment with lithium and valproate reversed the elevated exploratory activity
      of Gria1-/- mice. Valproate treatment also reduced struggling behaviour in tail
      suspension test and restored reciprocally-initiated social contacts of Gria1-/-
      mice to the level shown by the wild-type Gria1+/+ mice. Gria1-/- mice consumed
      slightly more sucrose during intermittent sucrose exposure than the wild-types,
      but ran similar distances on running wheels. These behaviours were not
      consistently affected by lithium and valproate in the Gria1-/- mice. The efficacy
      of various anti-manic drug treatments on novelty-induced hyperactivity suggests
      that the Gria1-/- mouse line can be utilized in screening for new therapeutics. 

PMID- 24932800
TI  - Oral 4-week and 13-week toxicity studies of polyvinyl acetate vinyl laurate
      copolymer in rats.
AB  - Polyvinyl acetate vinyl laurate copolymer (PVAcVL) is a useful component of gum
      base for chewing gum production. The safety of PVAcVL was examined in a 4-week
      and a 13-week oral toxicity study in rats. Finely powdered PVAcVL was
      administered with the diet at levels of 1.25%, 2.0% and 5% in the 4-week study
      and 1.25%, 2.5% and 5% in the 13-week study. There were no treatment related
      effects on mortality, bodyweight gains feed efficiency, ophthalmoscopic findings,
      hematological and clinical chemical parameters, neurobehavioral observations as
      well as gross and histopathological changes of standard organs and tissues. The
      highest dose tested in the 13-week study (3783 and 4396mg/kgbw/d for males and
      females, respectively) proved to be a NOAEL. 

PMID- 24932801
TI  - Generation of giant unilamellar liposomes containing biomacromolecules at
      physiological intracellular concentrations using hypertonic conditions.
AB  - Artificial cells, particularly cell-sized liposomes, serve as tools to improve
      our understanding of the physiological conditions of living cells. However, such
      artificial cells typically contain a more dilute solution of biomacromolecules
      than that found in living cells (300 mg mL(-1)). Here, we reconstituted the
      intracellular biomacromolecular conditions in liposomes using hyperosmotic
      pressure. Liposomes encapsulating 80 mg mL(-1) of macromolecules of BSA or a
      protein mixture extracted from Escherichia coli were immersed in hypertonic
      sucrose. The concentration of macromolecules in BSA-containing liposomes was
      increased in proportion to the initial osmotic pressure ratio between internal
      and external media. On the other hand, the concentration of the protein mixture
      in liposomes could be saturated to reach the physiological concentration of
      macromolecules in cells. Furthermore, membrane transformation after the
      hypertonic treatment differed between BSA- and protein mixture-containing
      liposomes. These results strongly suggested that the crowded environment in cells
      is different from that found in typical single-component systems. 

PMID- 24932802
TI  - miRNAs in circulation: mirroring bone conditions?

PMID- 24932803
TI  - In vivo tracing uptake and elimination of organic pesticides in fish muscle.
AB  - Bioconcentration factors (BCFs) measured in the laboratory are important for
      characterizing the bioaccumulative properties of chemicals entering the
      environment, especially the potential persistent organic pollutants (POPs), which
      can pose serious adverse effects on ecosystem and human health. Traditional
      lethal analysis methods are time-consuming and sacrifice too many experimental
      animals. In the present study, in vivo solid-phase microextraction (SPME) was
      introduced to trace the uptake and elimination processes of pesticides in living
      fish. BCFs and elimination kinetic coefficients of the pesticides were recorded
      therein. Moreover, the metabolism of fenthion was also traced with in vivo SPME.
      The method was time-efficient and laborsaving. Much fewer experimental animals
      were sacrificed during the tracing. In general, this study opened up an
      opportunity to measure BCFs cheaply in laboratories for the registering of
      emerging POPs and inspecting of suspected POPs, as well as demonstrated the
      potential application of in vivo SPME in the study of toxicokinetics of
      pollutants. 

PMID- 24932804
TI  - Histone deacetylase inhibition induces long-lasting changes in maternal behavior
      and gene expression in female mice.
AB  - In many species, including mice, maternal responsiveness is experience-dependent
      and permanent, lasting for long periods (months to years). We have shown that
      after brief exposures to pups, virgin female mice continue to respond maternally
      toward pups for at least one month. Administration of a histone deacetylase
      inhibitor (HDACi) reduces the amount of maternal experience required to affect
      maternal behavior and gene expression. In this set of studies, we examined the
      epigenetic mechanisms that underlie these motivated behaviors. We assessed
      whether the effects of HDACi persisted 1 month after the initial experience (in
      the absence of continued pup experience or HDACi treatment) and whether the
      maintenance of maternal memory was associated with stable changes in gene
      expression. Using chromatin immunoprecipitation, we examined whether Esr2 and Oxt
      gene expression might be mediated by recruitment of the histone acetyltransferase
      cAMP response element binding protein (CBP) to their promoter regions after
      maternal memory consolidation. We report that HDACi treatment induced long
      lasting changes in maternal responsiveness. Maternal learning was associated with
      increased recruitment of CBP to the Esr2 and Oxt gene promoters during the
      consolidation of maternal memory as well as a persistent increase in estrogen
      receptor-beta (Esr2) mRNA and decreased expression of the de novo DNA
      methyltransferase Dnmt3a within the medial preoptic area. The consolidation of
      the maternal experience may involve the CBP recruitment and stable changes in
      gene expression, which maintain increased maternal responsiveness for long
      periods of time. 

PMID- 24932805
TI  - Pancreatic beta-cell-specific ablation of TASK-1 channels augments glucose
      stimulated calcium entry and insulin secretion, improving glucose tolerance.
AB  - Calcium entry through voltage-dependent Ca(2+) channels (VDCCs) is required for
      pancreatic beta-cell insulin secretion. The 2-pore-domain acid-sensitive
      potassium channel (TASK-1) regulates neuronal excitability and VDCC activation by
      hyperpolarizing the plasma membrane potential (Deltapsip); however, a role for
      pancreatic beta-cell TASK-1 channels is unknown. Here we examined the influence
      of TASK-1 channel activity on the beta-cell Deltapsip and insulin secretion
      during secretagogue stimulation. TASK-1 channels were found to be highly
      expressed in human and rodent islets and localized to the plasma membrane of beta
      cells. TASK-1-like currents of mouse and human beta-cells were blocked by the
      potent TASK-1 channel inhibitor, A1899 (250nM). Although inhibition of TASK-1
      currents did not influence the beta-cell Deltapsip in the presence of low (2mM)
      glucose, A1899 significantly enhanced glucose-stimulated (14mM) Deltapsip
      depolarization of human and mouse beta-cells. TASK-1 inhibition also resulted in
      greater secretagogue-stimulated Ca(2+) influx in both human and mouse islets.
      Moreover, conditional ablation of mouse beta-cell TASK-1 channels reduced K2P
      currents, increased glucose-stimulated Deltapsip depolarization, and augmented
      secretagogue-stimulated Ca(2+) influx. The Deltapsip depolarization caused by
      TASK-1 inhibition resulted in a transient increase in glucose-stimulated mouse
      beta-cell action potential (AP) firing frequency. However, secretagogue
      stimulated beta-cell AP duration eventually increased in the presence of A1899 as
      well as in beta-cells without TASK-1, causing a decrease in AP firing frequency.
      Ablation or inhibition of mouse beta-cell TASK-1 channels also significantly
      enhanced glucose-stimulated insulin secretion, which improved glucose tolerance.
      Conversely, TASK-1 ablation did not perturb beta-cell Deltapsip, Ca(2+) influx,
      or insulin secretion under low-glucose conditions (2mM). These results reveal a
      glucose-dependent role for beta-cell TASK-1 channels of limiting glucose
      stimulated Deltapsip depolarization and insulin secretion, which modulates
      glucose homeostasis.

PMID- 24932806
TI  - A rapid cytoplasmic mechanism for PI3 kinase regulation by the nuclear thyroid
      hormone receptor, TRbeta, and genetic evidence for its role in the maturation of
      mouse hippocampal synapses in vivo.
AB  - Several rapid physiological effects of thyroid hormone on mammalian cells in
      vitro have been shown to be mediated by the phosphatidylinositol 3-kinase (PI3K),
      but the molecular mechanism of PI3K regulation by nuclear zinc finger receptor
      proteins for thyroid hormone and its relevance to brain development in vivo have
      not been elucidated. Here we show that, in the absence of hormone, the thyroid
      hormone receptor TRbeta forms a cytoplasmic complex with the p85 subunit of PI3K
      and the Src family tyrosine kinase, Lyn, which depends on two canonical
      phosphotyrosine motifs in the second zinc finger of TRbeta that are not conserved
      in TRalpha. When hormone is added, TRbeta dissociates and moves to the nucleus,
      and phosphatidylinositol (3, 4, 5)-trisphosphate production goes up rapidly.
      Mutating either tyrosine to a phenylalanine prevents rapid signaling through PI3K
      but does not prevent the hormone-dependent transcription of genes with a thyroid
      hormone response element. When the rapid signaling mechanism was blocked
      chronically throughout development in mice by a targeted point mutation in both
      alleles of Thrb, circulating hormone levels, TRbeta expression, and direct gene
      regulation by TRbeta in the pituitary and liver were all unaffected. However, the
      mutation significantly impaired maturation and plasticity of the Schaffer
      collateral synapses on CA1 pyramidal neurons in the postnatal hippocampus. Thus,
      phosphotyrosine-dependent association of TRbeta with PI3K provides a potential
      mechanism for integrating regulation of development and metabolism by thyroid
      hormone and receptor tyrosine kinases. 

PMID- 24932807
TI  - Rab5 activity regulates GLUT4 sorting into insulin-responsive and non-insulin
      responsive endosomal compartments: a potential mechanism for development of
      insulin resistance.
AB  - Glucose transporter isoform 4 (GLUT4) is the insulin-responsive glucose
      transporter mediating glucose uptake in adipose and skeletal muscle. Reduced
      GLUT4 translocation from intracellular storage compartments to the plasma
      membrane is a cause of peripheral insulin resistance. Using a chronic
      hyperinsulinemia (CHI)-induced cell model of insulin resistance and Rab5 mutant
      overexpression, we determined these manipulations altered endosomal sorting of
      GLUT4, thus contributing to the development of insulin resistance. We found that
      CHI induced insulin resistance in 3T3-L1 adipocytes by retaining GLUT4 in a Rab5
      activity-dependent compartment that is unable to equilibrate with the cell
      surface in response to insulin. Furthermore, CHI-mediated retention of GLUT4 in
      this non-insulin-responsive compartment impaired filling of the transferrin
      receptor (TfR)-positive and TfR-negative insulin-responsive storage compartments.
      Our data suggest that hyperinsulinemia may inhibit GLUT4 by chronically
      maintaining GLUT4 in the Rab5 activity-dependent endosomal pathway and impairing
      formation of the TfR-negative and TfR-positive insulin-responsive GLUT4 pools.
      This model suggests that an early event in the development of insulin-resistant
      glucose transport in adipose tissue is to alter the intracellular localization of
      GLUT4 to a compartment that does not efficiently equilibrate with the cell
      surface when insulin levels are elevated for prolonged periods of time. 

PMID- 24932809
TI  - Regulation of GLUT transporters by flavonoids in androgen-sensitive and 
      insensitive prostate cancer cells.
AB  - Cancer cells show different metabolic requirements from normal cells. In prostate
      cancer, particularly, glycolytic metabolism differs in androgen-responsive and
      nonresponsive cells. In addition, some natural compounds with antiproliferative
      activities are able to modify glucose entry into cells by either modulating
      glucose transporter (GLUT) expression or by altering glucose binding. The aim of
      this work was to study the regulation of some GLUTs (GLUT1 and GLUT4) in both
      androgen-sensitive (LNCaP) and -insensitive (PC-3) prostate cancer cells by 4
      structurally different flavonoids (ie, genistein, phloretin, apigenin, and
      daidzein). Glucose uptake was measured using nonradiolabeled 2-deoxyglucose. The
      evaluation of protein levels as well as subcellular distribution of GLUT1/4 were
      analyzed by Western blot and immunocytochemistry, respectively. Androgen
      insensitive LNCaP-R and androgen-sensitive PC-3-AR cells were used to study the
      effect of androgen signaling. Additionally, a docking simulation was employed to
      compare interactions between flavonoids and XylE, a bacterial homolog of GLUT1 to
      -4. Results show for the first time the presence of functionally relevant GLUT4
      in prostate cancer cells. Furthermore, differences in GLUT1 and GLUT4 levels and
      glucose uptake were found, without differences on subcellular distribution, after
      incubation with flavonoids. Docking simulation showed that all compounds interact
      with the same location of transporters. More importantly, differences between
      androgen-sensitive and -insensitive prostate cancer cells were found in both GLUT
      protein levels and glucose uptake. Thus, phenotypic characteristics of prostate
      cancer cells are responsible for the different effects of these flavonoids in
      glucose uptake and in GLUT expression rather than their structural differences,
      with the most effective in reducing cell growth being the highest in modifying
      glucose uptake and GLUT levels. 

PMID- 24932810
TI  - Phloridzin improves lipoprotein lipase activity in stress-loaded mice via AMPK
      phosphorylation.
AB  - Long-term stress exposure can lead to disturbed homeostasis and cause many life
      style diseases. Phloridzin possesses various bioactivities, but the understanding
      of the effects of phloridzin on stress-related lipid metabolism disorder is
      limited. Our results demonstrate that phloridzin improved plasma lipoprotein
      lipase (LPL) activity and triglyceride metabolism in restrained mice. A decrease
      of angiopoietin-like protein 4 (ANGPTL4) mRNA expression and an increase of AMP
      activated protein kinase (AMPK) phosphorylation were observed after phloridzin
      treatment. After inhibiting AMPK phosphorylation, the effects of phloridzin on
      the amelioration of plasma LPL activity and suppression of ANGPTL4 expression
      were blocked. In addition, cardiac AMPK phosphorylation, plasma LPL activity and
      ANGPTL4 expression were also affected by phloridzin, even if the glucocorticoid
      receptor was blocked. Taken together, the down-regulation of ANGPTL4 expression
      by phloridzin was probably via a direct activation of AMPK pathway. This
      discovery can provide a biochemical and nutritional basis for the use of
      phloridzin-containing food and beverage in daily life.

PMID- 24932808
TI  - Biochemical and cell biological properties of the human prohormone convertase 1/3
      Ser357Gly mutation: a PC1/3 hypermorph.
AB  - Satiety and appetite signaling are accomplished by circulating peptide hormones.
      These peptide hormones require processing from larger precursors to become
      bioactive, often by the proprotein convertase 1/3 (PC1/3). Several subcellular
      maturation steps are necessary for PC1/3 to achieve its optimal enzymatic
      activity. Certain PC1/3 variants found in the general population slightly
      attenuate its enzymatic activity and are associated with obesity and diabetes.
      However, mutations that increase PC1/3 activity and/or affect its specificity
      could also have physiological consequences. We here present data showing that the
      known human Ser357Gly PC1/3 mutant (PC1/3(S357G)) represents a PC1/3 hypermorph.
      Conditioned media from human embryonic kidney-293 cells transfected with
      PC1/3(WT) and PC1/3(S357G) were collected and enzymatic activity characterized.
      PC1/3(S357G) exhibited a lower calcium dependence; a higher pH optimum (neutral);
      and a higher resistance to peptide inhibitors than the wild-type enzyme.
      PC1/3(S357G) exhibited increased cleavage to the C-terminally truncated form, and
      kinetic parameters of the full-length and truncated mutant enzymes were also
      altered. Lastly, the S357G mutation broadened the specificity of the enzyme; we
      detected PC2-like specificity on the substrate proCART, the precursor of the
      cocaine- and amphetamine regulated transcript neuropeptide known to be associated
      with obesity. The production of another anorexigenic peptide normally synthesized
      only by PC2, alphaMSH, was increased when proopiomelanocortin was coexpressed
      with PC1/3(S357G). Considering the aberrant enzymatic profile of PC1/3(S357G), we
      hypothesize that this enzyme possesses unusual processing activity that may
      significantly change the profile of circulating peptide hormones. 

PMID- 24932812
TI  - Clinical outcome in heart transplant recipients receiving everolimus in
      combination with dosage reduction of the calcineurin inhibitor cyclosporine A or
      tacrolimus.
AB  - The mTOR inhibitor everolimus (EVL) can be used for calcineurin inhibitor-sparing
      immunosuppression in heart transplantation (HTx). However, comparable data
      regarding clinical outcomes in HTx recipients receiving EVL either with dosage
      reduction of cyclosporine A (CSA) or with dosage reduction of tacrolimus (TAC) is
      scarce. In a retrospective data analysis, we compared 5-year clinical outcomes in
      154 maintenance patients receiving EVL with CSA (n=106) or TAC (n=48). The
      primary endpoint was a composite of death, graft loss and EVL discontinuation
      (treatment failure). Secondary endpoints were kidney function, cardiac rejection,
      cytomegalovirus infection and biochemical safety parameters. In the CSA and TAC
      group, the primary endpoint was reached by 59.8% and 53.1%, respectively
      (P=0.716). Five-year mortality was 30.4% (CSA group) and 23.13% (TAC group),
      respectively (P=0.371), and freedom from EVL discontinuation was 53.3% and 59.6%
      (P=0.566) in the respective groups. Covariate-adjusted relative risk of treatment
      failure was in the CSA group=1.28 (95% CI: 0.70-2.34; P=0.43) compared with the
      TAC group. The course of covariate-adjusted estimated glomerular filtration rate
      and freedom from cytomegalovirus infection was similar in the two groups (P=0.502
      and P=0.476), whereas covariate-adjusted freedom from rejection was lower in the
      CSA group compared with the TAC group (P=0.023). Lipid status and blood cell
      counts were comparable between groups. In conclusion, data indicate that EVL plus
      reduced TAC is not superior to EVL plus reduced CSA regarding treatment failure
      and kidney function. However, compared with EVL plus reduced CSA, EVL plus
      reduced TAC seems to reduce cardiac rejections. 

PMID- 24932811
TI  - Late-onset neutropenia and acute rejection in ABO-incompatible kidney transplant
      recipients receiving rituximab and mycophenolate mofetil.
AB  - INTRODUCTION: Using rituximab, we have performed successful ABO-incompatible
      kidney transplantations in recipients without splenectomy as well as in those
      with high pretransplant anti-A/B antibody titers. A common and increasingly
      recognized toxicity of rituximab is late-onset neutropenia (LON), defined as
      unexplained grades III to IV neutropenia occurring at least 4weeks after the last
      dose of rituximab in the absence of an alternative explanation. PATIENTS AND
      METHODS: Between May 2006 and December 2011, 25 patients who received rituximab
      underwent successful ABO-incompatible kidney transplantation and were enrolled as
      the subjects in this study. The incidence rate and clinical features of LON as
      well as the relationship between LON and acute rejection in these patients were
      studied. RESULTS: Twelve recipients (48%) experienced LON 2 to 12months after
      transplantation. Five of the 12 patients (41.6%) who developed LON had an episode
      of biopsy-confirmed acute cellular rejection, as compared with one of the 13
      patients (7.7%) who did not develop LON. Moreover, 3 patients who experienced LON
      developed steroid and deoxyspergualin-resistant acute cellular rejection
      requiring OKT-3 administration. CONCLUSIONS: The frequency of acute cellular
      rejection was higher in ABO-incompatible kidney transplant recipients with LON
      than in those without LON. Our findings suggested that these recipients who
      developed LON after rituximab administration may be at an increased risk for
      acute cellular rejection.

PMID- 24932814
TI  - Pediatric sensorineural hearing loss.

PMID- 24932815
TI  - Endoscopic view of osteogenesis imperfecta of the maxilla.

PMID- 24932816
TI  - An unusual presentation of anterior subglottic stenosis.

PMID- 24932817
TI  - Rhabdomyosarcoma of the supraglottis in an adult.

PMID- 24932818
TI  - Mitek bone-anchored static suture suspension of the oral commissure.

PMID- 24932813
TI  - Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid
      synovium and its potential contribution to fibroblast platelet crosstalk.
AB  - INTRODUCTION: Synovial fibroblasts (SF) undergo phenotypic changes in rheumatoid
      arthritis (RA) that contribute to inflammatory joint destruction. This study was
      undertaken to evaluate the clinical and functional significance of ectopic
      podoplanin (gp38) expression by RA SF. METHODS: Expression of gp38 and its CLEC2
      receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies
      from RA patients and normal and osteoarthritic controls. Correlation between gp38
      expression and RA clinicopathological variables was analyzed. In patients
      rebiopsied after anti-TNF-alpha therapy, changes in gp38 expression were
      determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze
      the functional contribution of gp38 to SF migratory and invasive properties, and
      to SF platelet crosstalk. RESULTS: gp38 was abundantly but variably expressed in
      RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal
      RA variables, significantly increased gp38 expression was only found in patients
      with lymphoid neogenesis (LN), and RF or ACPA autoantibodies. Cultured synovial
      but not dermal fibroblasts showed strong constitutive gp38 expression that was
      further induced by TNF-alpha. In RA patients, anti-TNF-alpha therapy
      significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor
      expression was only observed in platelets. gp38 silencing in cultured SF did not
      modify their migratory and invasive properties but reduced the expression of IL-6
      and IL-8 genes induced by SF-platelet interaction. CONCLUSIONS: In RA, synovial
      expression of gp38 is strongly associated to LN and it is reduced after anti-TNF
      alpha therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible
      in RA synovium in vivo and can specifically contribute to gene expression by SF.

PMID- 24932819
TI  - Postauricular fascia in augmentation rhinoplasty.
AB  - Ten rhinoplasty operations performed using postauricular fascia for the purpose
      of augmenting the radix and dorsum of the nose were analyzed retrospectively. All
      the operations were performed over a 1-year period, between 2005 and 2006. The
      fascia of the postauricular area has been used as a source of pliable soft-tissue
      grafts in primary and revision rhinoplasty. It may be easily accessed using a
      single sulcus incision that also enables harvesting of ear cartilage grafts.
      Deficiency in the radix is an overlooked abnormality seen in many patients
      undergoing primary as well as revision rhinoplasty after aggressive hump removal.
      Recent trends in rhinoplasty have been to avoid the overly reduced nasal skeleton
      and to create a more balanced nasal surgery result. This article presents the use
      of the postauricular fascia as a radix graft that has been found to be simple to
      carry out, reliable, and long lasting. In addition, the fascia graft is useful in
      the camouflage of various nasal deformities in the dorsum and sidewalls. The
      average patient follow-up for the study was 24 months. 

PMID- 24932820
TI  - Condyloma acuminatum of the buccal mucosa.
AB  - Condyloma acuminatum is a human papillomavirus (HPV)-induced disease. It is
      usually transmitted sexually, and it frequently occurs in the anogenital area. A
      finding of condyloma acuminatum in the oral cavity is rare. Besides HPV, other
      risk factors for oral condyloma include chewing betel quid and smoking. We report
      the case of a 52-year-old man who presented with a 2 * 2-cm verrucous white patch
      on his buccal mucosa. He was habituated to both betel quid and cigarette smoking.
      A biopsy of the lesion identified it as a verrucous hyperplasia of the squamous
      epithelium with HPV-related koilocytic changes. The lesion was excised, and
      further histopathology identified it as condyloma acuminatum. The patient was
      disease-free 9 months postoperatively. The possibility of condyloma acuminatum
      should be considered in the differential diagnosis of an oral white lesion. The
      most common treatments are surgical excision, cryosurgery, electrocautery, and
      laser excision. There is no known role for antiviral therapy. 

PMID- 24932821
TI  - Ossifying fibromyxoid tumor metastatic to the thyroid: a case report and review
      of the literature.
AB  - Ossifying fibromyxoid tumors are rare soft-tissue neoplasms, usually with an
      indolent course. However, atypical/malignant variants have been described,
      showing either local recurrence after complete excision or metastasis to the
      lungs, mediastinum, adrenals, or soft tissue. We report the case of an ossifying
      fibromyxoid tumor of the left ankle that metastasized to the lung and thyroid
      gland 12 years after the initial diagnosis and surgical treatment. To our
      knowledge, this is the first reported case of this neoplasm metastasizing to the
      thyroid gland. 

PMID- 24932822
TI  - Report of a rare case of carcinosarcoma of the maxillary sinus with sternal
      metastasis.
AB  - Carcinosarcoma is a highly aggressive and infiltrative tumor. A finding of this
      tumor in a paranasal sinus is exceedingly rare. We describe the case of a 61-year
      old man who presented with a mass on the left side of his face. The mass was
      excised via a total maxillectomy with a modified radical neck dissection.
      Histologic analysis identified a mixture of carcinomatous and sarcomatous
      components. Within 1 month of surgery, the patient developed a sternal
      metastasis, and he died within a short period of time. The aggressive nature of
      this tumor and its metastases demand early diagnosis and prompt treatment. 

PMID- 24932823
TI  - Endoscopic management of spontaneous CSF rhinorrhea with septal graft and middle
      turbinate rotational flap technique: a review of 31 cases.
AB  - Spontaneous cerebrospinal fluid (CSF) rhinorrhea poses a major challenge to
      rhinologists. Much controversy attends its cause, pathophysiology, management,
      and prognosis. It has been suggested that endoscopic placement of a septal graft
      with a middle turbinate rotational flap may represent the ideal approach to
      closing skull base defects. We conducted a retrospective chart review to compile
      the results of this approach in 31 patients with spontaneous CSF rhinorrhea-22
      women and 9 men, aged 18 to 67 years (mean 38.5 +/- 8.96) at diagnosis. After one
      surgery, success had been achieved in 27 of these patients (87.1%). The remaining
      4 patients underwent a second surgery, and 2 of them experienced a successful
      closure. In the remaining 2 patients, a third surgery was still unsuccessful, and
      they were referred to the neurosurgical team for a shunt procedure. Thus, the
      overall success rate with the septal graft and a middle turbinate rotational flap
      was 93.5% (29/31). Septal grafts and middle turbinate flaps are easy to harvest
      and easy to place. Accurate localization of the defect, meticulous surgical
      technique, and cerebral dehydrating measures may improve outcomes. Further study
      of spontaneous CSF rhinorrhea to better evaluate its pathophysiology and
      prognostic factors is warranted. 

PMID- 24932824
TI  - Metastatic hepatocellular carcinoma presenting as a sphenoid sinus mass and
      meningeal carcinomatosis.
AB  - We report the case of a 30-year-old woman who was referred to us for evaluation
      of a 2-week history of fever, headache, vomiting, bilateral ptosis, and blurred
      vision. Imaging obtained by the referring institution had identified a sphenoid
      sinus mass and diffuse meningeal infiltration, which was thought to represent an
      infective process. We subsequently identified the mass as a metastatic
      hepatocellular carcinoma (HCC). The patient was placed under palliative care, and
      she died 1 month later. Metastases to the sphenoid sinus from any primary source
      are very rare, and they are generally not considered in the radiologic
      differential diagnosis. HCC is known to metastasize to the lung, lymph nodes, and
      musculoskeletal system; again, reported cases of metastasis to the sphenoid sinus
      are rare. Indeed, our review of the English-language literature found only 6
      previously reported cases of sinonasal metastasis of a primary HCC. A diagnosis
      of a sinonasal metastasis is more difficult in a patient who has no previous
      diagnosis of a primary malignancy. In presenting this case, our aim is to remind
      readers of this possibility. 

PMID- 24932825
TI  - Helical tomotherapy of the complete scalp and the ipsilateral lymph nodes in a
      case of scalp angiosarcoma.
AB  - Scalp angiosarcoma represents a therapeutic challenge to all disciplines. This
      case report demonstrates the potential usefulness of helical tomotherapy (HT) as
      a new radiotherapeutic treatment option. A 71-year-old woman presented with a
      superficial angiosarcoma of the scalp, forehead, and left pre- and postauricular
      areas, with several nodular ulcerating and bleeding lesions. Irradiation of the
      gross tumor was performed with a total dose of 70 Gy in 2-Gy fractions and of the
      left cervical lymph nodes with 56 Gy in 1.6-Gy fractions. Good target coverage
      was achieved without compromising organs at risk, notably the brain. Treatment
      was very fast (661 seconds per fraction) and was administered with minimal acute
      toxicity (National Cancer Institute Common Toxicity Criteria: grade 2 erythema
      and grade 2 dysphagia). During treatment, tumor nodules dissolved into
      hyperkeratosis. We conclude that with HT, irradiation of the scalp and cervical
      lymph nodes can be conducted with minimal acute toxicity and without junction
      problems. 

PMID- 24932826
TI  - Sebaceous carcinoma of the parotid gland: a case report and review of the
      literature.
AB  - Sebaceous carcinoma is a rare malignancy primarily affecting the periocular
      sebaceous glands. Sebaceous carcinoma of the parotid gland is exceedingly rare,
      with only 30 cases reported in the literature. Our case brings this total to 31.
      We present a case involving a 57-year-old man with a slowly enlarging, right tail
      of-parotid mass abutting the ear lobule with overlying skin discoloration.
      Excision of the mass with superficial parotidectomy was performed, and
      microscopic examination demonstrated sebaceous carcinoma with positive margins.
      Subsequently, the patient underwent a completion parotidectomy and inferior
      auriculectomy with no evidence of residual tumor. Six months after postoperative
      adjuvant radiotherapy, the patient remains tumor-free. The clinical and
      morphologic features of this tumor are discussed. 

PMID- 24932827
TI  - Nasal vestibule schwannoma: report of a rare case.
AB  - Schwannomas of the nasal cavity and paranasal sinuses are quite rare, especially
      in the nasal vestibule. We report the case of a 61-year-old woman who presented
      with a 2-month history of progressively worsening right-sided epistaxis and nasal
      blockage. Rigid nasoendoscopy showed a mobile, smooth, globular mass occupying
      the right nasal vestibule. The mass arose from the lateral nasal wall and
      impinged on the anterior part of the middle turbinate posteriorly. Computed
      tomography of the paranasal sinuses showed a 3.8 * 1.7-cm enhancing mass in the
      right nostril. The mass obliterated the nasal cavity and caused mild deviation of
      the septum. The preoperative histopathologic examination showed positivity for
      vimentin and S-100 protein, suggesting a diagnosis of schwannoma. The patient
      underwent an intranasal laser-assisted excision biopsy. The histopathologic
      examination confirmed the diagnosis of schwannoma. Postoperative recovery was
      uneventful, and no recurrence was seen in the follow-up period. 

PMID- 24932828
TI  - Harmonic Scalpel versus electrocautery and surgical clips in head and neck free
      flap harvesting.
AB  - We sought to determine the safety and utility of Harmonic Scalpel-assisted free
      flap harvesting as an alternative to a combined electrocautery and surgical clip
      technique. The medical records of 103 patients undergoing radial forearm free
      flap reconstruction (105 free flaps) for head and neck surgical defects between
      2006 and 2008 were reviewed. The use of bipolar electrocautery and surgical clips
      for division of small perforating vessels (n = 53) was compared to ultrasonic
      energy (Harmonic Scalpel; Ethicon Endo-Surgery, Inc., Cincinnati, Ohio) (n = 52)
      free-tissue harvesting techniques. Flap-harvesting time was reduced with the use
      of the Harmonic Scalpel when compared with electrocautery and surgical clip
      harvest (31.4 vs. 36.9 minutes, respectively; p = 0.06). Two patients who
      underwent flap harvest with electrocautery and surgical clips developed
      postoperative donor site hematomas, whereas no donor site complications were
      noted in the Harmonic Scalpel group. Recipient site complication rates for
      infection, fistula, and hematoma were similar for both harvesting techniques (p =
      0.77). Two flap failures occurred in the clip-assisted radial forearm free-flap
      harvest group, and none in the Harmonic Scalpel group. Median length of
      hospitalization was significantly reduced for patients who underwent free-flap
      harvest with the Harmonic Scalpel when compared with the other technique (7 vs. 8
      days; p = 0.01). The Harmonic Scalpel is safe, and its use is feasible for radial
      forearm free-flap harvest. 

PMID- 24932829
TI  - Extensive basal cell carcinoma of the face: an extreme case of denial.
AB  - Patients with head and neck cancer are particularly susceptible to using denial
      as a coping mechanism. While some forms of denial may help patients achieve
      better levels of physical functioning, persistent denial can serve as a major
      barrier to treatment. We report a case of extreme denial by a 60-year-old woman
      with an extensive basal cell carcinoma of the face that had been neglected for
      more than 20 years. We present this case to raise awareness of the potential
      danger of denial, and we discuss strategies that physicians can undertake to
      properly manage patients who engage in it. Since the diagnosis and treatment of
      head and neck cancer can result in profound psychological trauma, gaining an
      appreciation for how patients cope with it is an important part of the
      comprehensive care of head and neck oncology patients. 

PMID- 24932830
TI  - How do pediatric adenoidectomy and adenotonsillotomy influence maternal
      psychological status?
AB  - We conducted a study to determine the impact that pediatric adenoidectomy or
      adenotonsillotomy (adenoidectomy with a partial tonsillectomy) had on the short
      term psychological status of the children's mothers. Mothers of 100 treated
      children were examined with the 14-item Hospital Anxiety and Depression Scale
      (HADS) questionnaire immediately before the operation and 3 days afterward; to
      establish a baseline for control purposes, they completed another questionnaire
      10 days postoperatively. We also compiled data for the mothers' demographic
      information and the children's physical status. In the preoperative period, we
      found that (1) the anxiety scores of half the mothers were abnormal, (2)
      depression scores were higher in the adenotonsillotomy group, and (3) anxiety and
      depression scores were lower in the mothers with more education and in the
      mothers who had a personal or family history of previous surgery. At 3 days
      postoperatively, anxiety and depression scores were again lower in the more
      educated mothers, and lower in the absence of postoperative fever. We conclude
      that mothers whose children are undergoing adenoidectomy or adenotonsillotomy,
      particularly the latter, and those with less education may require some
      psychological intervention. Such help may also be needed when postoperative
      complications occur. 

PMID- 24932831
TI  - Bacteriology and antimicrobial susceptibility of ENT infections in a tropical
      hospital.
AB  - We conducted a retrospective observational study to determine the spectrum and
      antibiotic sensitivity pattern of organisms isolated in otorhinolaryngologic
      (ORL) infections. We reviewed the laboratory culture and sensitivity records of
      4,909 patients-2,773 males (56.5%) and 2,136 females (43.5%), aged 2 to 90 years
      (mean: 45.3 +/- 12.6)-who had been seen at two government hospitals in Malaysia.
      Of this group, 4,332 patients had a respiratory tract infection (88.2%), 206 had
      an ear infection (4.2%), 188 had a deep neck infection (3.8%), and 183 had an
      oropharyngeal infection (3.7%). The most common isolated organisms were
      Klebsiella spp, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus
      aureus, methicillin-susceptible S aureus, coagulase-negative S aureus, and
      Acinetobacter baumannii. We also identified the antimicrobial susceptibility of
      these organisms. We conclude that since the spectrum of causative pathogens in
      some infections differs between tropical and nontropical areas of the world,
      tropical hospitals should not completely adopt the antibiotic guidelines for ORL
      infections that have been recommended for hospitals in nontropical regions. We
      hope that our review and analysis of local data will help practitioners in
      Malaysia develop an appropriate prescribing policy with respect to ORL pathogens
      and antimicrobial susceptibility. The goal is to reduce the morbidity and
      mortality associated with these infections. 

PMID- 24932832
TI  - Automastoidectomy.

PMID- 24932833
TI  - An abnormal sigmoid sinus with a dire clinical implication.

PMID- 24932834
TI  - Metastatic ovarian sex-cord stromal tumor with annular tubules in a patient
      without Peutz-Jeghers syndrome.
AB  - Sex-cord stromal tumors (SCSTs) with annular tubules (SCTATs) are a small class
      of ovarian lesions that possess histologic features of both Sertoli and granulosa
      cells. Approximately one-third of patients with SCTAT also have Peutz-Jaghers
      syndreome, which makes these cases especially rare. Patients with non-PJS
      associated SCTAT make up the remaining two-thirds; 20% of these cases have a
      metastatic presentation. Metastasis of these tumors to the head and neck region
      has only been reported in a few instances. In this article we report a case of a
      25-year-old woman who presented with "a lump in her throat" and was ultimately
      diagnosed with SCTAT. We also discuss the current protocols in the diagnosis and
      treatment of this entity. 

PMID- 24932835
TI  - Synthesis of truncated analogues of preptin-(1-16), and investigation of their
      ability to stimulate osteoblast proliferation.
AB  - Preptin, a 34-amino acid residue peptide hormone is co-secreted with insulin from
      the beta-pancreatic cells and is active in fuel metabolism. We have previously
      established that a shorter fragment of preptin, namely preptin-(1-16), stimulates
      bone growth by proliferation and increasing the survival rate of osteoblasts.
      This was demonstrated in both in vitro and in vivo models. These findings suggest
      that preptin-(1-16) could play an important role in the anabolic therapy of
      osteoporosis. However, due to the large size of the peptide it is not an ideal
      therapeutic agent. The aim of this study was to identify the shortest preptin
      analogue that retains or even increases the bone anabolic activity as compared to
      the parent preptin-(1-16) peptide. Truncations were made in a methodical manner
      from both the N-terminus and the C-terminus of the peptide, and the effect of
      these deletions on the resulting biological activity was assessed. In order to
      improve the enzymatic stability of the shortest yet active analogue identified,
      ruthenium-catalysed ring closing metathesis was used to generate a macrocyclic
      peptide using allylglycine residues as handles for ring formation. We have
      successfully identified a short 8-amino acid preptin (1-8) fragment that retains
      an anabolic effect on the proliferation of primary rat osteoblasts and enhances
      bone nodule formation. Preptin (1-8) is a useful lead compound for the
      development of orally active therapeutics for the treatment of osteoporosis.

PMID- 24932837
TI  - Will management of appendicitis have the same fate as management of duodenal
      ulcer?

PMID- 24932836
TI  - Development of a simplified and convenient assay for cell-mediated immunity to
      the mumps virus.
AB  - Because methods for measuring cell-mediated immunity (CMI) to the mumps virus are
      expensive, time-consuming, and technically demanding, the role of CMI in mumps
      virus infection remains unclear. To address this issue, we report here the
      development of a simplified method for measuring mumps virus-specific CMI that is
      suitable for use in diverse laboratory and clinical settings. A mumps vaccine was
      cultured with whole blood, and interferon (IFN)-gamma released into the culture
      supernatant was measured using an enzyme-linked immunosorbent assay. IFN-gamma
      production in blood from vaccinated subjects markedly increased in response to
      the vaccine and decreased before the antibody titer decreased in some cases,
      suggesting that this assay may be used as a simple surrogate method for measuring
      CMI specific for the mumps virus. 

PMID- 24932838
TI  - Spectroscopy of homo- and heterodimers of silver and gold nanocubes as a function
      of separation: a DDA simulation.
AB  - The plasmonic fields of silver and gold nanocubes are known to be among the
      strongest of any plasmonic metallic nanoparticles. Aggregation dominates their
      use in imaging and sensing applications due to the resulting enhancement of the
      plasmonic field in between the nanoparticles (hot spots). The first step in the
      aggregation process is dimerization. In the present work, we used the discrete
      dipole approximation (DDA) to calculate the interdimer separation dependence of
      the absorption and scattering components of the localized surface plasmon
      resonance (LSPR) extinction of homo and heterodimers of Ag and Au nanocubes when
      excited parallel to their interparticle axis. We also examined the changes in the
      nanocube surface plasmonic field distributions as the dimer separation was
      varied. The results from the homodimers were as expected: as the cubes were
      brought together, there was a red shift in the primary plasmon band in accordance
      with the universal scaling law. Additionally, as the particles moved together,
      scattering contributed more to the overall extinction. By examining the E-field
      distributions, we found that the hot spot geometry changes abruptly at small
      separations. At very short distances, the hot spot is located between the
      adjacent faces and away from the corners of these faces. At larger separations it
      moves toward the adjacent corners. We observed apparently anomalous behavior for
      the heterodimer. First, the E-field resulting from excitation of the Ag dominated
      plasmon resonance was significantly weaker than expected. Second, the red shift
      of the gold dominated plasmon resonance did not follow the universal scaling law.
      The most likely explanation for these observations is that the silver plasmon
      mixes strongly with the energetically resonant, but nonplasmonic, gold interband
      transition to form a hybrid resonance that produces weaker overall field
      intensity on the two nanocubes at short separation. 

PMID- 24932839
TI  - Photochemical behavior of sethoxydim in the presence of vegetable oils.
AB  - The photodecomposition of herbicides may be affected by adding vegetable oils to
      the spray tank. In this study nine vegetable oils were compared to assess the
      photodecomposition of sethoxydim under natural light conditions. The experiment
      was conducted as completely randomized factorial design with three replicates at
      the College of Agriculture, Ferdowsi University of Mashhad, Iran, in 2013. Each
      herbicidal solution (with and without vegetable oil) was exposed to sunshine with
      time intervals of 0, 5, 10, 20, 30, 60, 120, and 240 min. The results revealed
      that the half-life value was increased by adding castor bean and cottonseed oils
      to 1.39- and 1.18-fold, respectively, compared to nonvegetable oil. These values
      for turnip, olive, corn, soybean, sunflower, canola, and sesame oils were
      decreased down to 4.74-, 2.38-, 1.81-, 1.75-, 1.52-, 1.28-, and 1.11-fold,
      respectively. A positive relationship existed between the half-life of sethoxydim
      in the presence of vegetable oils and their viscosity. However, a negative
      relationship was monitored between unsaturated/saturated fatty acids ratio and
      the monounsaturated value with half-life. A positive relationship also existed
      between saturated fatty acids, polyunsaturated fatty acids, palmitic acid, and
      linoleic acid with half-life. This study revealed that the amount of fatty acids
      in vegetable oils is a determining factor in preventing or facilitating the
      photodecomposition of sethoxydim. 

PMID- 24932841
TI  - An anionic aluminabenzene bearing aromatic and ambiphilic contributions.
AB  - The synthesis and structure of an anionic aluminabenzene, which is the first
      example of an aluminum-containing heterobenzene, are reported. The molecular
      structure of this aluminabenzene exhibits a planar six-membered ring, and the
      absence of any bond alternation between its unsaturated bonds is consistent with
      the structural criteria of aromaticity. Theoretical calculations and the NMR
      spectroscopic analysis of this anionic aluminabenzene furthermore suggest that,
      in addition to the aromatic conjugation of six pi-electrons, an ambiphilic
      contribution from a Lewis acidic aluminum center and an anionic pentadienyl
      moiety are present. Due to this contribution, the aluminabenzene is able to react
      with Lewis bases such as 4-dimethylaminopyridine and electrophiles such as methyl
      iodide. 

PMID- 24932840
TI  - The impact of insurance and socioeconomic status on outcomes for patients with
      left ventricular assist devices.
AB  - BACKGROUND: There has been a steady increase of patients living in the community
      with Left Ventricular Assist Devices (LVADs). There is a significant gap in our
      fund of knowledge with respect to the impact that insurance and socioeconomic
      status has on outcomes for LVAD patients. We thus hypothesize that low
      neighborhood socioeconomic status and receipt of Medicaid, respectively, lead to
      earlier readmissions, earlier death, as well as longer time to transplantation
      among LVAD patients. METHODS: This was a retrospective review of 101 patients
      using existing data in the medical information warehouse database at The Ohio
      State University Medical Center. Primary outcomes measured included time to first
      event (first readmission or death), death, and time to rehospitalization. Our
      secondary outcome of interest included time from LVAD implantation to cardiac
      transplantation. RESULTS: Recipients of Medicaid did not have an increased risk
      of adverse events compared with patients without Medicaid coverage. Low Median
      Household Income (MHI) was associated with an increased risk of readmission (log
      rank P = 0.0069) and time to first event (log-rank P = 0.0088). Bridge to
      transplantation was the only independent predictor of time to death (Hazard Ratio
      2.1, [95% confidence interval = 1.03-4.37]). Low MHI and a history of
      atherosclerosis were both significant predictors for readmission and time to
      first event. Aldosterone antagonist use decreased the risk of readmission or time
      to first event by 46%. CONCLUSIONS: LVAD recipients with a low MHI were more
      likely to be readmitted to the hospital after LVAD implantation. Whether these
      patients are adequately monitored on an outpatient basis remains unclear.

PMID- 24932843
TI  - Searching the expressive face: evidence for both the right hemisphere and valence
      specific hypotheses.
AB  - Quick and accurate judgments of emotional expressivity and attractiveness
      facilitate social interactions. Eye tracking was used to examine left/right
      asymmetries across 2 studies. Fixations to each hemiface, and to the eyes and
      mouth, when judging attractiveness and emotional expressivity were examined.
      Overall, more fixations occurred on the left hemiface (from the viewer's point of
      view), even when mirror-reversed, supporting the suggestion that we intuitively
      know the left hemiface is more expressive. The right side of the mouth was
      fixated more when judging happiness, whereas the left eye was fixated more for
      sadness and the left mouth when rating emotional expressivity. The present
      findings support the notion that the right hemisphere and valence-specific
      hypotheses are not mutually exclusive. The right hemisphere hypothesis is
      supported when assessing global facial qualities (i.e., hemiface); however,
      hemispheric processing differences emerge when exploring the eyes and mouth. The
      current findings highlight the importance of not only considering how the face is
      examined more generally, but of also exploring smaller regions of interest to
      investigate lateral biases. Future research should therefore include analyses of
      fixations to the hemifaces, as well as to these smaller regions of interest.

PMID- 24932842
TI  - How arousal modulates the visual contrast sensitivity function.
AB  - Recent evidence indicates that emotion enhances contrast thresholds in subsequent
      visual perception (Phelps, Ling, & Carrasco, 2006) and perceptual sensitivity for
      low-spatial frequency but not high-spatial frequency targets (Bocanegra &
      Zeelenberg, 2009b). However, these studies just report responses to various
      frequencies at a fixed contrast level or responses to various contrasts at a
      fixed frequency. In the current study, we measured the full contrast sensitivity
      function as a function of emotional arousal in order to investigate potential
      interactions between spatial frequency and contrast. We used a Bayesian adaptive
      inference with a trial-to-trial information gain strategy (Lesmes, Lu, Baek, &
      Albright, 2010) and a fear-conditioned stimulus to manipulate arousal level. The
      spatial frequency at which people showed peak contrast sensitivity shifted to
      lower spatial frequencies in the arousing condition compared with the nonarousing
      condition and people had greater contrast sensitivity function bandwidth in the
      arousing than in the nonarousing condition.

PMID- 24932844
TI  - Ultrasound-guided interventions in children.
AB  - There are a variety of available imaging modalities used for minimally invasive
      procedures in children, however, among the most frequently used is ultrasound
      (US). The advantages of US are vast and include real-time visualization, lack of
      ionizing radiation, and all-around versatility. US is also inexpensive, portable
      and widely available. In general US guided procedures in children have
      applications in nearly every aspect of medical therapy. Properly trained
      practitioners with US imaging experience and detailed knowledge of the relevant
      anatomy provide an invaluable service to the care of pediatric patients in many
      centers. This paper will discuss many of the image guided procedures that are
      performed in children and offer practical techniques from the collective
      experience of our practice at a large pediatric tertiary care center. 

PMID- 24932845
TI  - Basics, principles, techniques and modern methods in paediatric ultrasonography.
AB  - Ultrasonography (US) is the mainstay of paediatric Radiology. This review aims at
      revisiting basic US principles, to list specific needs throughout childhood, and
      to discuss the application of new and modern US methods. The various sections
      elude to basic US physics, technical requisites and tips for handling,
      diagnostically valuable applications of modern techniques, and how to properly
      address hazards, risks and limitations. In conclusion, US holds vast potential
      throughout childhood in almost all body regions and many childhood specific
      queries - helping to reduce the need for or to optimize more invasive or
      irradiating imaging. Make the most of US and offerings a dedicated paediatric US
      service throughout the day, the week and the year thus is and will stay a major
      task of Paediatric Radiology. 

PMID- 24932846
TI  - Low energy mammogram obtained in contrast-enhanced digital mammography (CEDM) is
      comparable to routine full-field digital mammography (FFDM).
AB  - PURPOSE: Contrast enhanced digital mammography (CEDM) uses low energy and high
      energy exposures to produce a subtracted contrast image. It is currently
      performed with a standard full-field digital mammogram (FFDM). The purpose is to
      determine if the low energy image performed after intravenous iodine injection
      can replace the standard FFDM. METHODS: And Materials: In an IRB approved HIPAA
      compatible study, low-energy CEDM images of 170 breasts in 88 women (ages 26-75;
      mean 50.3) undergoing evaluation for elevated risk or newly diagnosed breast
      cancer were compared to standard digital mammograms performed within 6 months.
      Technical parameters including posterior nipple line (PNL) distance, compression
      thickness, and compression force on the MLO projection were compared.
      Mammographic findings were compared qualitatively and quantitatively. Mixed
      linear regression using generalized estimating equation (GEE) method was
      performed. Intraclass correlation coefficients (ICC) with 95% confidence interval
      (95%CI) were estimated to assess agreement. RESULTS: No statistical difference
      was found in the technical parameters compression thickness, PNL distance,
      compression force (p-values: 0.767, 0.947, 0.089). No difference was found in the
      measured size of mammographic findings (p-values 0.982-0.988). Grouped
      calcifications had a mean size/extent of 2.1cm (SD 0.6) in the low-energy
      contrast images, and a mean size/extent of 2.2 cm (SD 0.6) in the standard
      digital mammogram images. Masses had a mean size of 1.8 cm (SD 0.2) in both
      groups. Calcifications were equally visible on both CEDM and FFDM. CONCLUSION:
      Low energy CEDM images are equivalent to standard FFDM despite the presence of
      intravenous iodinated contrast. Low energy CEDM images may be used for
      interpretation in place of the FFDM, thereby reducing patient dose.

PMID- 24932847
TI  - MRI evidence for preserved regulation of intracranial pressure in patients with
      cerebral arteriovenous malformations.
AB  - PURPOSE: The purpose of this study was to investigate intracranial pressure and
      associated hemo- and hydrodynamic parameters in patients with cerebral
      arteriovenous malformations AVMs. METHODS: Thirty consecutive patients with
      arteriovenous malformations (median age 38.7 years, 27/30 previously treated with
      radiosurgery) and 30 age- and gender-matched healthy controls were investigated
      on a 3.0T MR scanner. Nidus volume was quantified on dynamic MR angiography.
      Total arterial cerebral blood flow (tCBF), venous outflow as well as aqueductal
      and craniospinal stroke volumes were obtained using velocity-encoded cine-phase
      contrast MRI. Intracranial volume change during the cardiac cycle was calculated
      and intracranial pressure (ICP) was derived from systolic intracranial volume
      change (ICVC) and pulse pressure gradient. RESULTS: TCBF was significantly higher
      in AVM patients as compared to healthy controls (median 799 vs. 692 mL/min,
      p=0.007). There was a trend for venous flow to be increased in both the
      ipsilateral internal jugular vein (IJV, 282 vs. 225 mL/min, p=0.16), and in the
      contralateral IJV (322 vs. 285 mL/min, p=0.09), but not in secondary veins. There
      was no significant difference in median ICP between AVM patients and control
      subjects (6.9 vs. 8.6 mmHg, p=0.30) and ICP did not correlate with nidus volume
      in AVM patients (rho=-0.06, p=0.74). There was a significant positive correlation
      between tCBF and craniospinal CSF stroke volume (rho=0.69, p=0.02). CONCLUSIONS:
      The elevated cerebral blood flow in patients with AVMs is drained through an
      increased flow in IJVs but not secondary veins. ICP is maintained within ranges
      of normal and does not correlate with nidus volume.

PMID- 24932848
TI  - Intrinsic subtypes and tumor grades in breast cancer are associated with distinct
      3-D power Doppler sonographic vascular features.
AB  - PURPOSE: This study aimed to investigate the three-dimensional (3-D) power
      Doppler ultrasonographic (PDUS) vascular features of breast carcinoma according
      to intrinsic subtypes, nodal stage, and tumor grade. MATERIALS AND METHODS: Total
      115 receiving mastectomy breast carcinomas (mean size, 2.5 cm; range, 0.7-6.5
      cm), including 102 invasive ductal carcinomas (IDC), 10 ductal carcinomas in situ
      (DCIS), and 3 invasive lobular carcinomas (ILC) diagnosed after mastectomy, were
      used in this retrospective study. Sixty IDC had nodal status and histopathologic
      tumor grades available for analysis. Vascular features, including number of
      vascular trees (NV), longest path length (LPL), total vessel length (TVL), number
      of bifurcations (NB), distance metric (DM), inflection count metric (ICM), vessel
      diameter (VD), and vessel-to-volume ratio (VVR) were extracted using 3-D thinning
      method. The Mann-Whitney U test, Student's t-test, one-way ANOVA, and Kruskal
      Wallis test were performed as appropriate. RESULTS: There was no significant
      difference of vascular features among IDC, DCIS and ILC. Except VD, vascular
      features in luminal type were significantly lower compared to HER2-enriched or
      triple negative types (p<0.05). Compared to ER+ (estrogen receptor positive)
      tumors, all features in ER- (estrogen receptor negative) tumors were
      significantly higher (p<0.01). Despite some significantly higher vascular
      features in high grade IDC compared to low and intermediate grade, there was no
      significant correlation between vascular features and nodal stages. CONCLUSION:
      Differences in 3-D PDUS vascular features among intrinsic types of IDC are
      attributed to their ER status. Vascular features extracted by 3-D PDUS correlate
      with tumor grades but not nodal stage in IDC.

PMID- 24932849
TI  - Real world biodiversity-ecosystem functioning: a seafloor perspective.
AB  - The effective application of biodiversity-ecosystem function (BEF) research to
      societal needs amid the Anthropocene represents the next grand challenge for
      ecology. Biodiversity knowledge that is most meaningful to society must reconcile
      insights derived from theory with detailed experiments and broad-scale trends.
      This perspective requires science that addresses high species richness,
      redundancy, and natural variability, which simplified 'model systems' cannot
      mimic. Here, we illustrate solutions of biodiversity knowledge to management and
      societal problems that combine BEF with scaling experiments, analysis of BEF
      along environmental gradients, and mapping technologies. We primarily draw
      examples from biophysical interactions in seafloor environments, which cover 70%
      of the Earth and add significantly to global ecosystem functions and services. 

PMID- 24932850
TI  - Climate relicts and their associated communities as natural ecology and evolution
      laboratories.
AB  - Climate relicts, marginal populations that have become isolated via climate
      driven range shifts, preserve ecological and evolutionary histories that can span
      millennia. Studies point to climate relicts as 'natural laboratories' for
      investigating how long-term environmental change impacts species and populations.
      However, we propose that such research should be expanded to reveal how climate
      change affects 'interacting' species in ways that reshape community composition
      and evolution. Biotic interactions and their community and ecosystem effects are
      often genetically based and driven by associations with foundation species. We
      discuss evolution in climate relicts within the context of the emerging fields of
      community and ecosystem genetics, exploring the idea that foundation relicts are
      also natural community and ecosystem laboratories and windows to future
      landscapes.

PMID- 24932851
TI  - Scapholunate ligament reconstruction using a flexor carpi radialis tendon graft.
AB  - PURPOSE: To review the results of scapholunate ligament reconstruction using a
      flexor carpi radialis tendon graft. METHODS: We performed a retrospective review
      of 22 patients with post-traumatic scapholunate instability who were treated with
      a modification of the Brunelli, a flexor carpi radialis tendon graft. RESULTS:
      The mean follow-up was 61 months. The average age was 40 years. The average loss
      of flexion was 23 degrees  and of extension was 22 degrees  compared with the
      contralateral side. Grip strength averaged 67% of the nonoperated side. All
      patients except 2 returned to work. Degenerative changes were seen in 3 patients
      at the time of revision. Complications occurred in 2 patients and included
      avascular necrosis of the scaphoid. CONCLUSIONS: Perfect biomechanical
      reconstruction might not be possible for scapholunate dissociation. Our results
      show, however, that ligament reconstruction led to satisfactory results from the
      patient's point of view. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24932852
TI  - Cytomegalovirus-related hemorrhagic cystitis in an immunocompetent child.
AB  - Cytomegalovirus (CMV) infections are mostly seen in immunocompromised patients.
      However, unusual manifestations or complications of acquired CMV infections in
      immunocompetent patients are rarely reported. CMV-related hemorrhagic cystitis is
      extremely rare but should be considered even in immunocompetent patients. We
      present a case of a 3-year-old immunocompetent boy with intermittent, terminal
      gross hematuria lasting for 1 month. There was no history of genitourinary trauma
      or stone disease. Urine analysis revealed hematuria with eumorphic red blood
      cells and no proteinuria. Urine culture was negative. Ultrasonography showed
      increased bladder wall thickness and irregularity at inferior of bladder.
      Cystoscopy revealed hyperemia and edema. Histopathological examination was
      consistent with CMV infection, viral DNA by polymerase chain reaction in
      peripheral blood and urine were positive. Clinical, laboratory, and imaging
      features pointed towards hemorrhagic cystitis due to CMV. He was followed-up with
      no treatment. After 1 month, repeated investigations showed complete resolution
      of finding. This is a rare description of an immunocompetent child with CMV
      induced cystitis.

PMID- 24932853
TI  - Reducing unnecessary preoperative blood orders and costs by implementing an
      updated institution-specific maximum surgical blood order schedule and a remote
      electronic blood release system.
AB  - BACKGROUND: Using blood utilization data acquired from the anesthesia information
      management system, an updated institution-specific maximum surgical blood order
      schedule was introduced. The authors evaluated whether the maximum surgical blood
      order schedule, along with a remote electronic blood release system, reduced
      unnecessary preoperative blood orders and costs. METHODS: At a large academic
      medical center, data for preoperative blood orders were analyzed for 63,916
      surgical patients over a 34-month period. The new maximum surgical blood order
      schedule and the electronic blood release system (Hemosafe; Haemonetics Corp.,
      Braintree, MA) were introduced mid-way through this time period. The authors
      assessed whether these interventions led to reductions in unnecessary
      preoperative orders and associated costs. RESULTS: Among patients having surgical
      procedures deemed not to require a type and screen or crossmatch (n = 33,216),
      the percent of procedures with preoperative blood orders decreased by 38% (from
      40.4% [7,167 of 17,740 patients] to 25.0% [3,869 of 15,476 patients], P < 0.001).
      Among all hospitalized inpatients, the crossmatch-to-transfusion ratio decreased
      by 27% (from 2.11 to 1.54; P < 0.001) over the same time period. The proportion
      of patients who required emergency release uncrossmatched blood increased from
      2.2 to 3.1 per 1,000 patients (P = 0.03); however, most of these patients were
      having emergency surgery. Based on the realized reductions in blood orders,
      annual costs were reduced by $137,223 ($6.08 per patient) for surgical patients,
      and by $298,966 ($6.20/patient) for all hospitalized patients. CONCLUSION:
      Implementing institution-specific, updated maximum surgical blood order schedule
      directed preoperative blood ordering guidelines along with an electronic blood
      release system results in a substantial reduction in unnecessary orders and
      costs, with a clinically insignificant increase in requirement for emergency
      release blood transfusions.

PMID- 24932854
TI  - Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery
      Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine
      Model.
AB  - Stem cell therapy is currently being studied with a view to rescuing various
      neurological diseases. Such studies require not only the discovery of potent
      candidate cells but also the development of methods that allow optimal delivery
      of those candidates to the brain tissues. Given that the blood-brain barrier
      (BBB) precludes cells from entering the brain, the present study was designed to
      test whether hyperosmolar mannitol securely opens the BBB and enhances intra
      arterial cell delivery. A noninjured normal canine model in which the BBB was
      presumed to be closed was used to evaluate the feasibility and safety of the
      tested protocol. Autologous adipose tissue-derived pericytes with platelet
      derived growth factor receptor beta positivity were utilized. Cells were
      administered 5 min after mannitol pretreatment using one of following techniques:
      (1) bolus injection of a concentrated suspension, (2) continuous infusion of a
      diluted suspension, or (3) bolus injection of a concentrated suspension that had
      been shaken by repeated syringe pumping. Animals administered a concentrated cell
      suspension without mannitol pretreatment served as a control group. Vital signs,
      blood parameters, neurologic status, and major artery patency were kept stable
      throughout the experiment and the 1-month posttreatment period. Although ischemic
      lesions were noted on magnetic resonance imaging in several mongrel dogs with
      concentrated cell suspension, the injection technique using repeated syringe
      shaking could avert this complication. The cells were detected in both
      ipsilateral and contralateral cortices and were more frequent at the ipsilateral
      and frontal locations, whereas very few cells were observed anywhere in the brain
      when mannitol was not preinjected. These data suggest that intra-arterial cell
      infusion with mannitol pretreatment is a feasible and safe therapeutic approach
      in stable brain diseases such as chronic stroke. 

PMID- 24932855
TI  - Pneumocystis jiroveci pneumonia in patients receiving dasatinib treatment.
AB  - Dasatinib may cause various adverse effects such as myelosuppression and pleural
      effusion. It is well known that dasatinib may affect cellular immunity, which
      leads to the subsequent risk of a myriad of infections and viral reactivations,
      especially cytomegalovirus. Pneumocystis jiroveci pneumonia (PJP) is an
      opportunistic infection that typically occurs in immunocompromised hosts.
      Although pneumonia is not uncommon among dasatinib-treated patients, dasatinib
      associated PJP has been reported only once in the literature, without a
      description of the clinical details. We report herein two cases of PJP in
      patients receiving treatment containing dasatinib. One patient developed PJP at 7
      months following dasatinib in combination with chemotherapy for the treatment of
      acute lymphoblastic leukemia. The other patient developed pleural effusion and
      PJP at 2 years following dasatinib treatment for chronic myeloid leukemia. Both
      patients recovered well after management with sulfamethoxazole/trimethoprim. Our
      experience illustrates that PJP is a potentially important complication of
      dasatinib-based treatment. Raising clinical awareness is important as prompt
      diagnosis and timely management are the cornerstones of successful treatment. 

PMID- 24932856
TI  - Species identification of Mycobacterium abscessus subsp. abscessus and
      Mycobacterium abscessus subsp. bolletii using rpoB and hsp65, and susceptibility
      testing to eight antibiotics.
AB  - OBJECTIVES: To separate Mycobacterium abscessus subsp. bolletii from
      Mycobacterium abscessus subsp. abscessus using species identification, and to
      investigate the in vitro activity of amikacin, cefoxitin, imipenem, levofloxacin,
      moxifloxacin, clarithromycin, azithromycin, and linezolid against Mycobacterium
      abscessus. METHODS: Seventy M. abscessus isolates, previously identified by 16S
      rRNA sequencing, were further identified by comparative sequence analysis of rpoB
      and hsp65. Drug susceptibility testing was conducted using the microplate Alamar
      Blue assay in accordance with Clinical and Laboratory Standards Institute (CLSI)
      guidelines and interpreted using CLSI breakpoints. RESULTS: Of the 70 strains, 45
      (64%) were M. abscessus subsp. abscessus and 25 (36%) were M. abscessus subsp.
      bolletii. The majority of M. abscessus isolates were susceptible to azithromycin,
      amikacin, linezolid, and imipenem (M. abscessus subsp. abscessus: 93%, 98%, 93%,
      and 73%, respectively; M. abscessus subsp. bolletii: 96%, 96%, 80%, and 68%,
      respectively). Approximately half of the M. abscessus isolates were moderately
      susceptible to cefoxitin and moxifloxacin (M. abscessus subsp. abscessus 53% and
      49%; M. abscessus subsp. bolletii 72% and 68%). Nearly all the M. abscessus
      isolates were resistant to levofloxacin (M. abscessus subsp. abscessus 96%, M.
      abscessus subsp. bolletii 100%). Inducible clarithromycin resistance was found in
      M. abscessus. After 14 days of incubation, 83% M. abscessus subsp. abscessus and
      36% M. abscessus subsp. bolletii were resistant to clarithromycin. CONCLUSIONS:
      Using rpoB and hsp65, M. abscessus subsp. bolletii could be distinguished from M.
      abscessus subsp. abscessus. Amikacin and azithromycin showed excellent activity
      against M. abscessus in vitro. Imipenem, linezolid, cefoxitin, and moxifloxacin
      also showed good activity. Levofloxacin was inactive against M. abscessus.
      Although clarithromycin showed excellent activity against M. abscessus on day 3,
      inducible resistance occurred, and after 14 days clarithromycin showed little
      activity against M. abscessus subsp. abscessus, but still had good activity
      against M. abscessus subsp. bolletii.

PMID- 24932858
TI  - Durability of the efficacy of integrated care in schizophrenia: a five-year
      randomized controlled study.
AB  - OBJECTIVE: The aim of the study was to evaluate the durability of efficacy of the
      Integrated Care (IC) program in a Swedish context. The IC program is a person
      centered flexible assertive community treatment approach delivered through a
      novel mechanism: a resource group clinical microsystem for each patient. METHODS:
      All patients with schizophrenia in a Gothenburg urban-sector catchment area were
      randomly assigned to either the IC or the Rational Rehabilitation (RR) programs.
      Sixty-six patients were interviewed and assessed by independent interviewers
      before treatment, after treatment (24 months), and at follow-up (five years).
      Analysis was by intention to treat. RESULTS: At the five-year follow-up,
      significant improvements were noted in social functioning and consumer
      satisfaction in the IC group (N=35) compared with the RR group (N=31). No
      patients were lost to services in either program. CONCLUSIONS: The major finding
      was the durability of efficacy of the IC program.

PMID- 24932860
TI  - Rapid fibroblast activation in mammalian cells induced by silicon nanowire
      arrays.
AB  - Activated tumor-associated fibroblasts (TAFs) with abundant fibroblast activation
      protein (FAP) expression attract tremendous attention in tumor progression
      studies. In this work, we report a rapid 24 h FAP activation method for
      fibroblasts using silicon nanowires (SiNWs) as culture substrates instead of
      growth factors or chemokines. In contrast with cells cultured on flat silicon
      which rarely express FAP, SiNW cultivated cells exhibit FAP levels similar to
      those found in cancerous tissue. We demonstrated that activated cells grown on
      SiNWs maintain their viability and proliferation in a time-dependent manner.
      Moreover, environmental scanning electron microscopy (ESEM) and focused ion beam
      and scanning electron microscopy (FIB-SEM) analysis clearly revealed that
      activated cells on SiNWs adapt to the structure of their substrates by filling
      inter-wire cavities via filopodia in contrast to cells cultured on flat silicon
      which spread freely. We further illustrated that the expression of FAP was rarely
      detected in activated cells after being re-cultured in Petri dishes, suggesting
      that the unique structure of SiNWs may have a certain influence on FAP
      activation. 

PMID- 24932857
TI  - Brain processing of emotional scenes in aging: effect of arousal and affective
      context.
AB  - Research on emotion showed an increase, with age, in prevalence of positive
      information relative to negative ones. This effect is called positivity effect.
      From the cerebral analysis of the Late Positive Potential (LPP), sensitive to
      attention, our study investigated to which extent the arousal level of negative
      scenes is differently processed between young and older adults and, to which
      extent the arousal level of negative scenes, depending on its value, may
      contextually modulate the cerebral processing of positive (and neutral) scenes
      and favor the observation of a positivity effect with age. With this aim, two
      negative scene groups characterized by two distinct arousal levels (high and low)
      were displayed into two separate experimental blocks in which were included
      positive and neutral pictures. The two blocks only differed by their negative
      pictures across participants, as to create two negative global contexts for the
      processing of the positive and neutral pictures. The results show that the
      relative processing of different arousal levels of negative stimuli, reflected by
      LPP, appears similar between the two age groups. However, a lower activity for
      negative stimuli is observed with the older group for both tested arousal levels.
      The processing of positive information seems to be preserved with age and is also
      not contextually impacted by negative stimuli in both younger and older adults.
      For neutral stimuli, a significantly reduced activity is observed for older
      adults in the contextual block of low-arousal negative stimuli. Globally, our
      study reveals that the positivity effect is mainly due to a modulation, with age,
      in processing of negative stimuli, regardless of their arousal level. It also
      suggests that processing of neutral stimuli may be modulated with age, depending
      on negative context in which they are presented to. These age-related effects
      could contribute to justify the differences in emotional preference with age. 

PMID- 24932861
TI  - Underpinning sustainable vector control through informed insecticide resistance
      management.
AB  - BACKGROUND: There has been rapid scale-up of malaria vector control in the last
      ten years. Both of the primary control strategies, long-lasting pyrethroid
      treated nets and indoor residual spraying, rely on the use of a limited number of
      insecticides. Insecticide resistance, as measured by bioassay, has rapidly
      increased in prevalence and has come to the forefront as an issue that needs to
      be addressed to maintain the sustainability of malaria control and the drive to
      elimination. Zambia's programme reported high levels of resistance to the
      insecticides it used in 2010, and, as a result, increased its investment in
      resistance monitoring to support informed resistance management decisions.
      METHODOLOGY/PRINCIPAL FINDINGS: A country-wide survey on insecticide resistance
      in Zambian malaria vectors was performed using WHO bioassays to detect resistant
      phenotypes. Molecular techniques were used to detect target-site mutations and
      microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was
      resistant to pyrethroids, DDT and carbamates, with potential organophosphate
      resistance in one population. The resistant phenotypes were conferred by both
      target-site and metabolic mechanisms. Anopheles funestus s.s. was largely
      resistant to pyrethroids and carbamates, with potential resistance to DDT in two
      locations. The resistant phenotypes were conferred by elevated levels of
      cytochrome p450s. CONCLUSIONS/SIGNIFICANCE: Currently, the Zambia National
      Malaria Control Centre is using these results to inform their vector control
      strategy. The methods employed here can serve as a template to all malaria
      endemic countries striving to create a sustainable insecticide resistance
      management plan.

PMID- 24932862
TI  - Quantitative detection of 8-Oxo-7,8-dihydro-2'-deoxyguanosine using chemical
      tagging and qPCR.
AB  - 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is a commonly formed DNA lesion
      that is useful as a biomarker for oxidative stress. Although methods for
      selective quantification of 8-oxodGuo exist, there is room for additional methods
      that are sensitive and utilize instrumentation that is widely available. We
      previously took advantage of the reported reactivity of 8-oxodGuo to develop a
      method for detecting the lesion by selectively covalently tagging it with a
      molecule equipped with a biotin label that can be used subsequently with a
      reporting method ( Xue , L. and Greenberg , M. M. ( 2007 ) J. Am. Chem. Soc. 129
      , 7010 ). We now report a method that can detect as little as 14 amol of 8
      oxodGuo by tagging DNA with a reagent containing a disulfide that reduces
      background due to nonspecific binding. The reagent also contains biotin that
      enables capturing target DNA on streptavidin-coated magnetic beads. The captured
      DNA is quantified using quantitative PCR. The method is validated by comparing
      the amount of 8-oxodGuo detected as a function of Fe(2+)/H2O2/ascorbate-dose to
      that reported previously using mass spectrometry. 

PMID- 24932863
TI  - MRI shows limited mixing between systemic and pulmonary circulations in foetal
      transposition of the great arteries: a potential cause of in utero pulmonary
      vascular disease.
AB  - OBJECTIVES: To investigate the relationship between foetal haemodynamics and
      postnatal clinical presentation in patients with transposition of the great
      arteries using phase-contrast cardiovascular magnetic resonance. BACKGROUND: A
      severe and irreversible form of persistent pulmonary hypertension of the newborn
      occurs in up to 5% of patients with transposition and remains an important cause
      of morbidity and mortality in these infants. Restriction at the foramen ovale and
      ductus arteriosus has been identified as a risk factor for the development of
      pulmonary hypertension, and this can now be studied with magnetic resonance
      imaging using a new technique called metric optimised gating. METHODS: Blood flow
      was measured in the major vessels of four foetuses with transposition with intact
      ventricular septum (gestational age range: 35-38 weeks) and compared with values
      from 12 normal foetuses (median gestational age: 37 weeks; range: 34-40 weeks).
      RESULTS: We found significantly reduced flows in the ductus arteriosus (p<0.01)
      and foramen ovale (p=0.03) and increased combined ventricular output (p=0.01),
      ascending aortic (p=0.001), descending aortic (p=0.03), umbilical vein (p=0.03),
      and aorto-pulmonary collateral (p<0.001) flows in foetuses with transposition
      compared with normals. The foetus with the lowest foramen ovale shunt and highest
      aorto-pulmonary collateral flow developed fatal pulmonary vascular disease.
      CONCLUSIONS: We found limited mixing between the systemic and pulmonary
      circulations in a small group of late-gestation foetuses with transposition. We
      propose that the resulting hypoxia of the pulmonary circulation could be the
      driver behind increased aorto-pulmonary collateral flow and contribute to the
      development of pulmonary vascular disease in some foetuses with transposition.

PMID- 24932864
TI  - Stereo camera based virtual cane system with identifiable distance tactile
      feedback for the blind.
AB  - In this paper, we propose a new haptic-assisted virtual cane system operated by a
      simple finger pointing gesture. The system is developed by two stages:
      development of visual information delivery assistant (VIDA) with a stereo camera
      and adding a tactile feedback interface with dual actuators for guidance and
      distance feedbacks. In the first stage, user's pointing finger is automatically
      detected using color and disparity data from stereo images and then a 3D pointing
      direction of the finger is estimated with its geometric and textural features.
      Finally, any object within the estimated pointing trajectory in 3D space is
      detected and the distance is then estimated in real time. For the second stage,
      identifiable tactile signals are designed through a series of identification
      experiments, and an identifiable tactile feedback interface is developed and
      integrated into the VIDA system. Our approach differs in that navigation guidance
      is provided by a simple finger pointing gesture and tactile distance feedbacks
      are perfectly identifiable to the blind. 

PMID- 24932866
TI  - Occupancy grid mapping in urban environments from a moving on-board stereo-vision
      system.
AB  - Occupancy grid map is a popular tool for representing the surrounding
      environments of mobile robots/intelligent vehicles. Its applications can be dated
      back to the 1980s, when researchers utilized sonar or LiDAR to illustrate
      environments by occupancy grids. However, in the literature, research on vision
      based occupancy grid mapping is scant. Furthermore, when moving in a real dynamic
      world, traditional occupancy grid mapping is required not only with the ability
      to detect occupied areas, but also with the capability to understand dynamic
      environments. The paper addresses this issue by presenting a stereo-vision-based
      framework to create a dynamic occupancy grid map, which is applied in an
      intelligent vehicle driving in an urban scenario. Besides representing the
      surroundings as occupancy grids, dynamic occupancy grid mapping could provide the
      motion information of the grids. The proposed framework consists of two
      components. The first is motion estimation for the moving vehicle itself and
      independent moving objects. The second is dynamic occupancy grid mapping, which
      is based on the estimated motion information and the dense disparity map. The
      main benefit of the proposed framework is the ability of mapping occupied areas
      and moving objects at the same time. This is very practical in real applications.
      The proposed method is evaluated using real data acquired by our intelligent
      vehicle platform "SeTCar" in urban environments. 

PMID- 24932865
TI  - Disposable screen printed electrochemical sensors: tools for environmental
      monitoring.
AB  - Screen printing technology is a widely used technique for the fabrication of
      electrochemical sensors. This methodology is likely to underpin the progressive
      drive towards miniaturized, sensitive and portable devices, and has already
      established its route from "lab-to-market" for a plethora of sensors. The
      application of these sensors for analysis of environmental samples has been the
      major focus of research in this field. As a consequence, this work will focus on
      recent important advances in the design and fabrication of disposable screen
      printed sensors for the electrochemical detection of environmental contaminants.
      Special emphasis is given on sensor fabrication methodology, operating details
      and performance characteristics for environmental applications. 

PMID- 24932867
TI  - Suitability evaluation of multipoint simultaneous CO2 sampling wireless sensors
      for livestock buildings.
AB  - The environment in livestock buildings must be controlled to ensure the health
      and welfare of both workers and animals, as well as to restrict the emission of
      pollutants to the atmosphere. Among the pollutants generated inside these
      premises, carbon dioxide (CO2) is of great interest in terms of animal welfare
      and ventilation control. The use of inexpensive sensors means that complete
      systems can be designed with a number of sensors located around the building.
      This paper describes a study of the suitability of multipoint simultaneous CO2
      sensors operating in a wireless sensor network, which was found to operate
      satisfactorily under laboratory conditions and was found to be the best
      alternative for these applications. The sensors showed a highly linear response
      to CO2 concentrations, ranging from 500 to 5000 ppm. However, individual sensor
      response was found to differ, which made it necessary to calibrate each one
      separately. Sensor precision ranged between 80 and 110 ppm CO2, and sensor
      response to register a 95% change in concentration was estimated at around 5 min.
      These features mean this type of sensor network can be used to monitor animal
      welfare and also for environmental control in poorly ventilated livestock
      premises. According to the tests conducted in this study, a temporal drift may
      occur and therefore a regular calibration of sensors would be needed. 

PMID- 24932868
TI  - Simulation and implementation of a morphology-tuned gold nano-islands integrated
      plasmonic sensor.
AB  - This work presents simulation, analysis and implementation of morphology tuning
      of gold nano-island structures deposited by a novel convective assembly
      technique. The gold nano-islands were simulated using 3D Finite-Difference Time
      Domain (FDTD) techniques to investigate the effect of morphological changes and
      adsorption of protein layers on the localized surface plasmon resonance (LSPR)
      properties. Gold nano-island structures were deposited on glass substrates by a
      novel and low-cost convective assembly process. The structure formed by an
      uncontrolled deposition method resulted in a nano-cluster morphology, which was
      annealed at various temperatures to tune the optical absorbance properties by
      transforming the nano-clusters to a nano-island morphology by modifying the
      structural shape and interparticle separation distances. The dependence of the
      size and the interparticle separation distance of the nano-islands on the LSPR
      properties were analyzed in the simulation. The effect of adsorption of protein
      layer on the nano-island structures was simulated and a relation between the
      thickness and the refractive index of the protein layer on the LSPR peak was
      presented. Further, the sensitivity of the gold nano-island integrated sensor
      against refractive index was computed and compared with the experimental results.

PMID- 24932869
TI  - Improving short term instability for quantitative analyses with portable
      electronic noses.
AB  - One of the main problems when working with electronic noses is the lack of
      reproducibility or repeatability of the sensor response, so that, if this problem
      is not properly considered, electronic noses can be useless, especially for
      quantitative analyses. On the other hand, irreproducibility is increased with
      portable and low cost electronic noses where laboratory equipment like gas zero
      generators cannot be used. In this work, we study the reproducibility of two
      portable electronic noses, the PEN3 (commercial) and CAPINose (a proprietary
      design) by using synthetic wine samples. We show that in both cases short term
      instability associated to the sensors' response to the same sample and under the
      same conditions represents a major problem and we propose an internal
      normalization technique that, in both cases, reduces the variability of the
      sensors' response. Finally, we show that the normalization proposed seems to be
      more effective in the CAPINose case, reducing, for example, the variability
      associated to the TGS2602 sensor from 12.19% to 2.2%. 

PMID- 24932871
TI  - Early maladaptive schema-related impairment and co-occurring current major
      depressive episode-related enhancement of mental state decoding ability in
      borderline personality disorder.
AB  - Disturbed interpersonal relationships specific to borderline personality disorder
      (BPD) suggest biased processing of social information. The goal of this study was
      to examine alterations in mental state decoding (MSD) and their associations with
      early maladaptive schemas (EMS) that may lead to the misinterpretation of
      incoming information. In addition, the authors' aim was to evaluate the effects
      of a co-occurring current major depressive episode (MDE) on the MSD performance
      of BPD patients. Seventy-eight BPD patients (34 with MDE) and 76 matched healthy
      controls (HC) were assessed for Reading the Mind in the Eyes Test (RMET) and the
      level of EMS. The authors found that impairment in the total RMET performance, as
      well as specific impairment regarding the recognition of positive and neutral
      items, was associated with EMS, and enhanced vigilance to negative mental states
      was characteristic to BPD with MDE. Results suggest that MSD ability is altered
      in two independent ways in BPD. 

PMID- 24932870
TI  - Freshwater-borne bacteria isolated from a Malaysian rainforest waterfall
      exhibiting quorum sensing properties.
AB  - One obvious requirement for concerted action by a bacterial population is for an
      individual to be aware of and respond to the other individuals of the same
      species in order to form a response in unison. The term "quorum sensing" (QS) was
      coined to describe bacterial communication that is able to stimulate expression
      of a series of genes when the concentration of the signaling molecules has
      reached a threshold level. Here we report the isolation from aquatic environment
      of a bacterium that was later identified as Enterobacter sp.. Chromobacterium
      violaceum CV026 and Escherichia coli [pSB401] were used for preliminary screening
      of N-acyl homoserine lactone (AHL) production. The Enterobacter sp. isolated was
      shown to produce two types of AHLs as confirmed by analysis using high resolution
      tandem mass spectrometry. To the best of our knowledge, this is the first
      documentation of an Enterobacter sp. that produced both 3-oxo-C6-HSL and 3-oxo-C8
      HSL as QS signaling molecules. 

PMID- 24932872
TI  - Diagnostic value of the Dutch version of the McLean Screening Instrument for BPD
      (MSI-BPD).
AB  - Borderline personality disorder (BPD) often goes unrecognized, and therefore a
      short but accurate screening tool is desired. The present study investigated the
      psychometric properties of the 10-item McLean Screening Instrument for BPD (MSI
      BPD) in 159 well-diagnosed female participants. The MSI-BPD showed excellent
      internal consistency (alpha = .90). When compared to BPD diagnoses based on a
      structured clinical interview (SCID-II), the MSI-BPD showed substantial congruent
      validity (receiver operating characteristic area under the curve = 0.96). The
      cutoff point proposed by the developers of the MSI-BPD (7 or more) showed high
      specificity (.96) and good sensitivity (.71). The optimal cutoff point in the
      present study (5 or more) showed somewhat lower specificity (.86), but
      importantly better sensitivity (.94). Taken together, the Dutch version of the
      MSI-BPD demonstrated good psychometric properties for a screening tool. 

PMID- 24932873
TI  - Association between childhood maltreatment and normal adult personality traits:
      exploration of an understudied field.
AB  - We assessed normal personality traits and childhood trauma in approximately 1170
      subjects from a general population-based community sample. In bivariate analyses
      emotional abuse was most pervasively related to personality, showing significant
      detrimental associations with neuroticism, extraversion, openness,
      conscientiousness, and agreeableness. Neuroticism was significantly related to
      emotional abuse and neglect, physical abuse and neglect, and sexual abuse.
      Emotional abuse was related to neuroticism in men more profoundly than in women
      (beta = 0.095). Adjusting for the covariance between childhood maltreatment
      variables, neuroticism was mainly related to emotional abuse (beta = 0.193),
      extraversion to emotional neglect (beta = -0.259), openness to emotional abuse
      (beta = 0.175), conscientiousness to emotional abuse (beta = -0.110), and
      agreeableness to emotional neglect (beta = -0.153). The proportion of variance
      explained was highest in neuroticism (5.6%) and lowest in openness (1.9%) and
      conscientiousness (1.8%). These findings help to understand the complex
      association between childhood maltreatment and both normal and pathological
      personality. 

PMID- 24932875
TI  - Affective empathy differs in male violent offenders with high- and low-trait
      psychopathy.
AB  - This study investigated affective and cognitive empathic processes in
      incarcerated violent offenders with lower and higher psychopathic traits and
      healthy controls. Participants witnessed painful expressions of others displayed
      on video clips. Skin conductance responses (SCR) were recorded to assess
      autonomic emotional arousal, and various empathy ratings were used as measures of
      self-reported vicarious responses. Reduced SCRs occurred during the observation
      of pain in others in lower and higher psychopathic-trait participants alike,
      compared to controls. Despite these diminished autonomic responses indicating
      reduced vicarious responses, only inmates with higher psychopathic traits
      provided empathy ratings comparable to those of the controls. These findings
      indicate that violent offenders display reduced autonomic arousal in response to
      distress cues of others, irrespective of psychopathy. However, only higher
      psychopathic-trait offenders were able to provide self-report in a way that let
      them appear to be as empathic as controls-enabling them to know, yet not to feel,
      what others feel. 

PMID- 24932874
TI  - A triarchic model analysis of the youth psychopathic traits inventory.
AB  - The Triarchic model of psychopathy characterizes this complex condition in terms
      of distinct phenotypic constructs of boldness, meanness, and disinhibition. The
      current study evaluated the coverage of these constructs provided by a well
      established inventory for assessing psychopathy in adolescents, the Youth
      Psychopathic Traits Inventory (YPI). A consensus rating approach was used to
      identify YPI items relevant to each Triarchic model construct, and convergent and
      discriminant validity of the resulting YPI-Triarchic scales were examined in
      relation to criterion measures consisting of scores on other psychopathy measures
      and relevant personality trait variables (N = 618, M age = 18.8). The YPI
      Triarchic scales showed good internal consistency and exhibited properties
      largely consistent with predictions based on the Triarchic model, aside from
      somewhat greater than expected covariance between boldness and other facet
      scales. Findings are discussed in terms of their implications for interpreting
      scores on the YPI and for investigating distinctive components of psychopathy in
      youth. 

PMID- 24932876
TI  - Severity of anxiety symptoms reported by borderline patients and Axis II
      comparison subjects: description and prediction over 16 years of prospective
      follow-up.
AB  - The first purpose of this study was to determine the severity of anxiety symptoms
      reported by borderline patients and Axis II comparison subjects over 16 years of
      follow-up. The second purpose was to determine the most salient predictors of the
      severity of anxiety symptoms of borderline patients. Initially, 290 borderline
      inpatients and 72 comparison subjects were assessed using measures of anxiety,
      childhood adversity, and normal personality. The severity of anxiety symptoms was
      reassessed every 2 years. Borderline patients reported approximately twice as
      severe symptoms of anxiety as comparison subjects. However, these symptoms
      decreased significantly over time for those in both groups. Among borderline
      patients, two variables were found to be significant multivariate predictors of
      severity of overall anxiety: nonsexual childhood abuse and trait neuroticism. The
      results of this study suggest that anxiety symptoms form a distinct profile for
      borderline patients-a profile related to both childhood adversity and a
      vulnerable temperament. 

PMID- 24932877
TI  - New pharmacological approaches for cystic fibrosis: promises, progress, pitfalls.
AB  - With the discovery of the CFTR gene in 1989, the search for therapies to improve
      the basic defects of cystic fibrosis (CF) commenced. Pharmacological manipulation
      provides the opportunity to enhance CF transmembrane conductance regulator (CFTR)
      protein synthesis and/or function. CFTR modulators include potentiators to
      improve channel gating (class III mutations), correctors to improve abnormal CFTR
      protein folding and trafficking (class II mutations) and stop codon mutation read
      through drugs relevant for patients with premature stop codons (most class I
      mutations). After several successful clinical trials the potentiator, ivacaftor,
      is now licenced for use in adults and children (>six years), with CF bearing the
      class III G551D mutation and FDA licence was recently expanded to include 8
      additional class III mutations. Alternative approaches for class I and class II
      mutations are currently being studied. Combination drug treatment with correctors
      and potentiators appears to be required to restore CFTR function of F508del, the
      most common CFTR mutation. Alternative therapies such as gene therapy and
      pharmacological modulation of other ion channels may be advantageous because they
      are mutation-class independent, however progress is less well advanced. Clinical
      trials for CFTR modulators have been enthusiastically embraced by patients with
      CF and health care providers. Whilst novel trial end-points are being evaluated
      allowing CFTR modulators to be efficiently tested, many challenges related to the
      complexity of CFTR and the biology of the epithelium still need to be overcome. 

PMID- 24932878
TI  - Formation of nanosized islands of dialkyl beta-ketoester bonds for efficient
      hydrophobization of a cellulose film surface.
AB  - The efficient hydrophobization mechanism of a hydrophilic cellulose film surface
      with alkylketene dimer (AKD) was studied in terms of formation of beta-ketoester
      bonds at AKD/cellulose interfaces and their nanosized distribution analysis. AKD
      treated cellulose and nanocellulose films were sequentially extracted with
      chloroform, hot water, and dioxane/water. Atomic force microscopy and high
      resolution secondary-ion mass spectrometry were used to analyze the surface
      structures of the AKD-treated cellulose films and those after the sequential
      extraction. The results showed that the AKD molecules had melted and transformed
      into spherical nanoparticles, ~37 nm in diameter, on the film surface during heat
      treatment, forming "sea/island"-like structures; the film surface projection area
      comprised 99% hydrophilic cellulose and 1% hydrophobic AKD nanoparticles.
      Determination of the AKD contents in the films revealed that an extremely small
      amount of AKD/cellulose beta-ketoester bonds were likely to form at the
      AKD/cellulose interfaces during heating, clearly contributing to the hydrophobic
      nature of the sequentially extracted cellulose films. 

PMID- 24932880
TI  - Association between sugar-sweetened and artificially sweetened soft drinks and
      type 2 diabetes: systematic review and dose-response meta-analysis of prospective
      studies.
AB  - The intake of sugar-sweetened soft drinks has been reported to be associated with
      an increased risk of type 2 diabetes, but it is unclear whether this is because
      of the sugar content or related lifestyle factors, whether similar associations
      hold for artificially sweetened soft drinks, and how these associations are
      related to BMI. We aimed to conduct a systematic literature review and dose
      response meta-analysis of evidence from prospective cohorts to explore these
      issues. We searched multiple sources for prospective studies on sugar-sweetened
      and artificially sweetened soft drinks in relation to the risk of type 2
      diabetes. Data were extracted from eleven publications on nine cohorts.
      Consumption values were converted to ml/d, permitting the exploration of linear
      and non-linear dose-response trends. Summary relative risks (RR) were estimated
      using a random-effects meta-analysis. The summary RR for sugar-sweetened and
      artificially sweetened soft drinks were 1.20/330 ml per d (95 % CI 1.12, 1.29, P<
      0.001) and 1.13/330 ml per d (95 % CI 1.02, 1.25, P= 0.02), respectively. The
      association with sugar-sweetened soft drinks was slightly lower in studies
      adjusting for BMI, consistent with BMI being involved in the causal pathway.
      There was no evidence of effect modification, though both these comparisons
      lacked power. Overall between-study heterogeneity was high. The included studies
      were observational, so their results should be interpreted cautiously, but
      findings indicate a positive association between sugar-sweetened soft drink
      intake and type 2 diabetes risk, attenuated by adjustment for BMI. The trend was
      less consistent for artificially sweetened soft drinks. This may indicate an
      alternative explanation, such as lifestyle factors or reverse causality. Future
      research should focus on the temporal nature of the association and whether BMI
      modifies or mediates the association.

PMID- 24932881
TI  - Cloning and characteristic analysis of a novel aspartic protease gene Asp55 from
      Trichoderma asperellum ACCC30536.
AB  - Proteases secreted by fungi belonging to the genus Trichoderma play important
      roles in biocontrol. In this study, the coding sequence and promoter region of
      the novel aspartic protease gene Asp55 were cloned from strain Trichoderma
      asperellum ACCC30536. Many cis-elements involved in phytopathogenic and
      environmental stress responses were identified in the Asp55 promoter region and
      may be recognized by MYB or WRKY transcription factors. The expression pattern of
      Asp55 under eight culture conditions was investigated by RT-qPCR. The expression
      level of Asp55 was up-regulated by poplar stem powder, Alternaria alternata cell
      wall fragments and A. alternata fermentation liquid, while it was down-regulated
      by carbon and nitrogen source starvation, and by powdered poplar leaves and
      roots. Additionally, the expression patterns of 15 genes encoding MYB
      transcription factors (Myb1 to Myb15) were also analyzed by RT-qPCR. Myb2 showed
      the most similar expression pattern with Asp55. The cDNA of Asp55 was expressed
      in Escherichia coli BL21, and recombinant ASP55 (rASP55) was purified. The
      purified rASP55 was evaluated for enzymatic activity and showed inhibitory effect
      on phytopathogenic A. alternata. 

PMID- 24932882
TI  - Diversity and distribution of planktonic anaerobic ammonium-oxidizing bacteria in
      the Dongjiang River, China.
AB  - Anaerobic ammonium-oxidizing (anammox) process has recently been recognized as an
      important pathway for removing fixed nitrogen (N) from aquatic ecosystems.
      Anammox organisms are widely distributed in freshwater environments. However,
      little is known about their presence in the water column of riverine ecosystems.
      Here, the existence of a diverse anammox community was revealed in the water
      column of the Dongjiang River by analyzing 16S rRNA and hydrazine oxidation (hzo)
      genes of anammox bacteria. Phylogenetic analyses of hzo genes showed that
      Candidatus Jettenia related clades of anammox bacteria were dominant in the
      river, suggesting the ecological microniche distinction from freshwater/estuary
      and marine anammox bacteria with Ca. Brocadia and Kuenenia genera mainly detected
      in freshwater/estuary ecosystems, and Ca. Scalindua genus mainly detected in
      marine ecosystems. The abundance and diversity of anammox bacteria along the
      river were both significantly correlated with concentrations of NH4(+)-N based on
      Pearson and partial correlation analyses. Redundancy analyses showed the contents
      of NH4(+)-N, NO3(-)-N and the ratio of NH4(+)-N to NO2(-)-N significantly
      influenced the spatial distributions of anammox bacteria in the water column of
      the Dongjiang River. These results expanded our understanding of the distribution
      and potential roles of anammox bacteria in the water column of the river
      ecosystem. 

PMID- 24932883
TI  - Improved ethanol tolerance of Saccharomyces cerevisiae in mixed cultures with
      Kluyveromyces lactis on high-sugar fermentation.
AB  - The influence of non-Saccharomyces yeast, Kluyveromyces lactis, on metabolite
      formation and the ethanol tolerance of Saccharomyces cerevisiae in mixed cultures
      was examined on synthetic minimal medium containing 20% glucose. In the late
      stage of fermentation after the complete death of K. lactis, S. cerevisiae in
      mixed cultures was more ethanol-tolerant than that in pure culture. The
      chronological life span of S. cerevisiae was shorter in pure culture than mixed
      cultures. The yeast cells of the late stationary phase both in pure and mixed
      cultures had a low buoyant density with no significant difference in the non
      quiescence state between both cultures. In mixed cultures, the glycerol contents
      increased and the alanine contents decreased when compared with the pure culture
      of S. cerevisiae. The distinctive intracellular amino acid pool concerning its
      amino acid concentrations and its amino acid composition was observed in yeast
      cells with different ethanol tolerance in the death phase. Co-cultivation of K.
      lactis seems to prompt S. cerevisiae to be ethanol tolerant by forming opportune
      metabolites such as glycerol and alanine and/or changing the intracellular amino
      acid pool. 

PMID- 24932885
TI  - The role of vascular endothelial growth factor in pulmonary arterial
      hypertension. The angiogenesis paradox.
AB  - Pulmonary arterial hypertension (PAH) is characterized by dysfunctional
      angiogenesis leading to lung vessel obliteration. PAH is widely considered a
      proangiogenic disease; however, the role of angiogenic factors, such as the
      vascular endothelial growth factor (VEGF) and its receptors, in the pathobiology
      of PAH remains incompletely understood. This Review attempts to untangle some of
      the complex multilayered actions of VEGF to provide a VEGF-centered perspective
      of PAH. Furthermore, we provide a cogent explanation for the paradox of VEGF
      receptor blockade-induced pulmonary hypertension that characterizes the SU5416
      hypoxia rat model of PAH, and attempt to translate the knowledge gained from the
      experimental model to the human disease by postulating the potential role of
      endogenous (SU5416-like) VEGF inhibitors. The main objective of this Review is to
      promote discussion and investigation of the opposing and complementary actions of
      VEGF in PAH. Understanding the balance between angiogenic and antiangiogenic
      factors and their role in the pathogenesis of PAH will be necessary before
      antiangiogenic drugs can be considered for the treatment of PAH. 

PMID- 24932884
TI  - Impact of gene molecular evolution on phylogenetic reconstruction: a case study
      in the rosids (Superorder Rosanae, Angiosperms).
AB  - Rate of substitution of genomic regions is among the most debated intrinsic
      features that impact phylogenetic informativeness. However, this variable is also
      coupled with rates of nonsynonymous substitutions that underscore the nature and
      degree of selection on the selected genes. To empirically address these
      variables, we constructed four completely overlapping data sets of plastid matK,
      atpB, rbcL, and mitochondrial matR genes and used the rosid lineage (angiosperms)
      as a working platform. The genes differ in combinations of overall rates of
      nucleotide and amino acid substitutions. Tree robustness, homoplasy, accuracy in
      contrast to a reference tree, and phylogenetic informativeness are evaluated. The
      rapidly evolving/unconstrained matK faired best, whereas remaining genes varied
      in degrees of contribution to rosid phylogenetics across the lineage's 108
      million years evolutionary history. Phylogenetic accuracy was low with the slowly
      evolving/unconstrained matR despite least amount of homoplasy. Third codon
      positions contributed the highest amount of parsimony informative sites,
      resolution and informativeness, but magnitude varied with gene mode of evolution.
      These findings are in clear contrast with the views that rapidly evolving regions
      and the 3rd codon position have inevitable negative impact on phylogenetic
      reconstruction at deep historic level due to accumulation of multiple hits and
      subsequent elevation in homoplasy and saturation. Relaxed evolutionary constraint
      in rapidly evolving genes distributes substitutions across codon positions, an
      evolutionary mode expected to reduce the frequency of multiple hits. These
      findings should be tested at deeper evolutionary histories. 

PMID- 24932886
TI  - Pharmacological and behavioral management of some often-overlooked clozapine
      induced side effects.
AB  - This article reviews four of the milder but still bothersome side effects of
      clozapine that are fairly frequent and may have a negative impact on patients'
      compliance with the treatment regime. We reviewed the available literature on the
      rate and management of four non-life-threatening side effects of clozapine,
      including hypersalivation, constipation, tachycardia, and nocturnal enuresis. We
      found a variety of pharmacological and behavioral strategies to manage these four
      side effects. There is, however, no consensus on a preferred strategy to control
      these distressing side effects and there are no guidelines. Psychiatrists should
      be aware of the relatively high rate of hypersalivation, constipation,
      tachycardia, and nocturnal enuresis in clozapine-treated patients, of the impact
      that these side effects may have on patients' quality of life, and should be able
      to suggest management strategies to the patients. 

PMID- 24932888
TI  - Epidemiology of granulomatosis with polyangiitis (Wegener's granulomatosis) in
      Northern Italy: a 15-year population-based study.
AB  - OBJECTIVE: To investigate the epidemiology of granulomatosis with polyangiitis
      (GPA) over a 15-year period in a defined area of northern Italy. METHODS: All
      patients with incident GPA diagnosed from January 1, 1995 to December 31, 2009
      living in the Reggio Emilia area were identified by looking at computerized
      hospital discharge diagnoses, by contacting Reggio Emilia Hospital physicians and
      community-based specialists, and by checking the databases of the pathology and
      the laboratory departments and the Reggio Emilia district database for rare
      diseases. Patients were classified according to the European Medicines Agency
      (EMA) algorithm. Patients were followed up from the time of diagnosis until
      either their death or December 31, 2011. For each case, we identified 20 control
      subjects from the same geographic area matched for age and gender. RESULTS: A
      total of 18 patients (7 men and 11 women) with GPA were identified. The overall
      age- and sex-adjusted incidence rate (IR) was 2.4 per million (95% CI: 1.2-3.5).
      The mean annual IR increased from 1.7/million/year during 1995-1999 to 3.4 during
      2005-2009. The highest IR occurred in females aged 70-79 years (13.5 per million;
      95% CI: 5.0-30.0) and in males aged >= 80 years (14.9 per million; 95% CI: 2.5
      49.4). The prevalence of GPA on December 31, 2009 was 34.3 per million (95% CI:
      20.3-54.2). The point prevalence per million increased from 17.8 (95% CI: 7.7
      35.1) in 1999 to 34.3 (95% CI: 20.3-54.2) in 2009. Survival among individuals
      with GPA was significantly reduced compared to that observed in the matched
      control population (p < 0.001). CONCLUSION: In the Italian population, GPA is
      very uncommon and GPA patients have reduced survival.

PMID- 24932889
TI  - Psoriatic arthritis and nail changes: exploring the relationship.
AB  - OBJECTIVE: Psoriatic arthritis (PsA) has a diverse range of clinical
      manifestations, both articular and extra-articular. Although the association of
      PsA with skin changes is well established, the relationship of PsA with psoriatic
      nail changes remains relatively unexplored. METHODS: This report reviews the
      current literature surrounding the association of PsA with nail changes. A review
      of the literature was completed using PubMed, MEDLINE, and EMBASE in September
      2013, encompassing years 1964-2012. RESULTS: A total of 21 articles were
      reviewed. On average, 66% [standard deviation (SD) 17.7] of PsA patients had nail
      changes. The type of nail changes and their associations varied widely between
      studies. CONCLUSIONS: Studies of nail changes in PsA are highly variable with a
      wide range of results. Given the variability of results that were observed in
      this review, our recommendations are that further large studies on nail changes
      in patients with PsA should be conducted.

PMID- 24932890
TI  - Synthesis and optical properties of dioxolane-functionalized hexacenes and
      heptacenes.
AB  - The synthesis of dioxolane-functionalized hexacenes and heptacenes is reported.
      While heptacenes were too reactive to be successfully isolated, hexacenes showed
      higher stability and characteristic long-wavelength fluorescence both in solution
      and in the solid state as crystalline powders. 

PMID- 24932887
TI  - Multivalent antiviral XTEN-peptide conjugates with long in vivo half-life and
      enhanced solubility.
AB  - XTENs are unstructured, nonrepetitive protein polymers designed to prolong the in
      vivo half-life of pharmaceuticals by introducing a bulking effect similar to that
      of poly(ethylene glycol). While XTEN can be expressed as a recombinant fusion
      protein with bioactive proteins and peptides, therapeutic molecules of interest
      can also be chemically conjugated to XTEN. Such an approach permits precise
      control over the positioning, spacing, and valency of bioactive moieties along
      the length of XTEN. We have demonstrated the attachment of T-20, an anti
      retroviral peptide indicated for the treatment of HIV-1 patients with multidrug
      resistance, to XTEN. By reacting maleimide-functionalized T-20 with cysteine
      containing XTENs and varying the number and positioning of cysteines in the
      XTENs, a library of different peptide-polymer combinations were produced. The T
      20-XTEN conjugates were tested using an in vitro antiviral assay and were found
      to be effective in inhibiting HIV-1 entry and preventing cell death, with the
      copy number and spacing of the T-20 peptides influencing antiviral activity. The
      peptide-XTEN conjugates were also discovered to have enhanced solubilities in
      comparison with the native T-20 peptide. The pharmacokinetic profile of the most
      active T-20-XTEN conjugate was measured in rats, and it was found to exhibit an
      elimination half-life of 55.7 +/- 17.7 h, almost 20 times longer than the
      reported half-life for T-20 dosed in rats. As the conjugation of T-20 to XTEN
      greatly improved the in vivo half-life and solubility of the peptide, the XTEN
      platform has been demonstrated to be a versatile tool for improving the
      properties of drugs and enabling the development of a class of next-generation
      therapeutics. 

PMID- 24932891
TI  - The 3-dimensional, 4-channel model of human visual sensitivity to grayscale
      scrambles.
AB  - Previous research supports the claim that human vision has three dimensions of
      sensitivity to grayscale scrambles (textures composed of randomly scrambled
      mixtures of different grayscales). However, the preattentive mechanisms (called
      here "field-capture channels") that confer this sensitivity remain obscure. The
      current experiments sought to characterize the specific field-capture channels
      that confer this sensitivity using a task in which the participant is required to
      detect the location of a small patch of one type of grayscale scramble in an
      extended background of another type. Analysis of the results supports the
      existence of four field-capture channels: (1) the (previously characterized)
      "blackshot" channel, sharply tuned to the blackest grayscales; (2) a (previously
      unknown) "gray-tuned" field-capture channel whose sensitivity is zero for black
      rising sharply to maximum sensitivity for grayscales slightly darker than mid
      gray then decreasing to half-height for brighter grayscales; (3) an "up-ramped"
      channel whose sensitivity is zero for black, increases linearly with increasing
      grayscale reaching a maximum near white; (4) a (complementary) "down-ramped"
      channel whose sensitivity is maximal for black, decreases linearly reaching a
      minimum near white. The sensitivity functions of field-capture channels (3) and
      (4) are linearly dependent; thus, these four field-capture channels collectively
      confer sensitivity to a 3-dimensional space of histogram variations. 

PMID- 24932892
TI  - Mobile phone reminders for paediatric HIV follow-up care.

PMID- 24932893
TI  - Effect of mobile phone reminders on follow-up medical care of children exposed to
      or infected with HIV in Cameroon (MORE CARE): a multicentre, single-blind,
      factorial, randomised controlled trial.
AB  - BACKGROUND: Missed scheduled HIV appointments lead to increased mortality,
      resistance to antiretroviral therapy, and suboptimum virological response. We
      aimed to assess whether reminders sent to carers by text message, mobile phone
      call, or concomitant text message and mobile phone call increase attendance at
      medical appointments for HIV care in a population of children infected with or
      exposed to HIV in Cameroon. We also aimed to ascertain the most cost-effective
      method of mobile-phone-based reminder. METHODS: MORE CARE was a multicentre,
      single-blind, factorial, randomised controlled trial in urban, semi-urban, and
      rural settings in Cameroon. Carers of children who were infected with or had been
      exposed to HIV were randomly assigned electronically in blocks of four and
      allocated (1:1:1:1) sequentially to receive a text message and a call, a text
      message only, a call only, or no reminder (control). Investigators were masked to
      group assignment. Text messages were sent and calls made 2 or 3 days before a
      scheduled follow-up appointment. The primary outcomes were efficacy (the
      proportion of patients attending a previously scheduled appointment) and
      efficiency (attendance/[measures of staff working time * cost of the reminders]),
      as a measure of cost-effectiveness. The primary analysis was by intention to
      treat. This study is registered with the Pan African Clinical Trials Register,
      number PACTR201304000528276. FINDINGS: The study took place between Jan 28 and
      May 24, 2013. We randomly assigned 242 adult-child (carer-patient) pairs into
      four groups: text message plus call (n=61), call (n=60), text message (n=60), and
      control (n=61). 54 participants (89%) in the text message plus call group, 51
      (85%) in the call group, 45 (75%) in the text message group, and 31 (51%) in the
      control group attended their scheduled appointment. Compared with control, the
      odds ratios for improvement in the primary efficacy outcome were 7.5 (95% CI 2.9
      19.0; p<0.0001) for text message plus call, 5.5 (2.3-13.1; p=0.0002) for call,
      and 2.9 (1.3-6.3; p=0.012) for text message. No significant differences were seen
      in comparisons of the three intervention groups with each other, and there was no
      synergism between text messages and calls. For the primary efficiency outcome,
      the mean difference for text message versus text message plus call was 1.5 (95%
      CI 0.7 to 2.4; p=0.002), for call versus text message plus call was 1.2 (0.7 to
      1.6; p<0.0001), and for call versus text message was 0.4 (-1.3 to 0.6; p=0.47).
      INTERPRETATION: Mobile-phone-based reminders of scheduled HIV appointments for
      carers of paediatric patients in low-resource settings can increase attendance.
      The most effective method of reminder was text message plus phone call, but text
      messaging alone was the most efficient (ie, cost-effective) method. FUNDING: No
      external funding.

PMID- 24932894
TI  - Comparison of neurodegeneration and cognitive impairment in neonatal mice exposed
      to propofol or isoflurane.
AB  - BACKGROUND: While previous studies have demonstrated neuronal apoptosis and
      associated cognitive impairment after isoflurane or propofol exposure in neonatal
      rodents, the effects of these two anesthetics have not been directly compared.
      Here, we compare and contrast the effectiveness of isoflurane and propofol to
      cause neurodegeneration in the developing brain and associated cognitive
      dysfunction. METHODS: Seven-day-old mice were used. Mice in the isoflurane
      treatment group received 6 h of 1.5% isoflurane, while mice in propofol treatment
      group received one peritoneal injection (150 mg/kg), which produced persistent
      anesthesia with loss of righting for at least 6 h. Mice in control groups
      received carrying gas or a peritoneal injection of vehicle (intralipid). At 6 h
      after anesthetic treatment, a subset of each group was sacrificed and examined
      for evidence of neurodegeneration, using plasma levels of S100beta, and apoptosis
      using caspase-3 immunohistochemistry in the cerebral cortex and hippocampus and
      Western blot assays of the cortex. In addition, biomarkers for inflammation
      (interleukin-1, interleukin-6, and tumor necrosis factor alpha) were examined
      with Western blot analyses of the cortex. In another subset of mice, learning and
      memory were assessed 32 days after the anesthetic exposures using the Morris
      water maze. RESULTS: Isoflurane significantly increased plasma S100beta levels
      compared to controls and propofol. Both isoflurane and propofol significantly
      increased caspase-3 levels in the cortex and hippocampus, though isoflurane was
      significantly more potent than propofol. However, there were no significant
      differences in the inflammatory biomarkers in the cortex or in subsequent
      learning and memory between the experimental groups. CONCLUSION: Both isoflurane
      and propofol caused significant apoptosis in the mouse developing brain, with
      isoflurane being more potent. Isoflurane significantly increased levels of the
      plasma neurodegenerative biomarker, S100beta. However, these neurodegenerative
      effects of isoflurane and propofol in the developing brain were not associated
      with effects on inflammation or with cognitive dysfunction in later life.

PMID- 24932896
TI  - Ecological momentary assessment of acute alcohol use disorder symptoms:
      associations with mood, motives, and use on planned drinking days.
AB  - Several theories posit that alcohol is consumed both in relation to one's mood
      and in relation to different motives for drinking. However, there are mixed
      findings regarding the role of mood and motives in predicting drinking.
      Ecological momentary assessment (EMA) methods provide an opportunity to evaluate
      near real-time changes in mood and motives within individuals to predict alcohol
      use. In addition, endorsement of criteria of an alcohol use disorder (AUD) may
      also be sensitive to changes within subjects. The current study used EMA with 74
      moderate drinkers who responded to fixed and random mood, motive, alcohol use,
      and AUD criteria prompts over a 21-day assessment period. A temporal pattern of
      daytime mood, evening drinking motivation, and nighttime alcohol use and acute
      AUD symptoms on planned drinking days was modeled to examine how these
      associations unfold throughout the day. The results suggest considerable
      heterogeneity in drinking motivation across drinking days. Additionally, an
      affect regulation model of drinking to cope with negative mood was observed.
      Specifically, on planned drinking days, the temporal association between daytime
      negative mood and the experience of acute AUD symptoms was mediated via coping
      motives and alcohol use. The current study found that motives are dynamic, and
      that changes in motives may predict differential drinking patterns across days.
      Further, the study provides evidence that emotion-regulation-driven alcohol
      involvement may need to be examined at the event level to fully capture the ebb
      and flow of negative affect motivated drinking.

PMID- 24932897
TI  - Male brush-turkeys attempt sexual coercion in unusual circumstances.
AB  - Sexual coercion by males is generally understood to have three forms: forced
      copulation, harassment and intimidation. We studied Australian brush-turkeys,
      Alectura lathami, to determine whether some male behaviours towards females at
      incubation mounds could be classified as aggressive, whether males were
      attempting sexual coercion and, if so, whether the coercion was successful. We
      found that some male behaviours towards females were significantly more likely to
      be followed by the cessation of female mound activity, and hence could be
      classified as aggressive, while others were significantly more likely to be
      followed by the commencement of female mound activity, and hence could be
      classified as enticing. Copulation was preceded by higher rates of male
      enticement and by higher rates of certain types of male aggression. It therefore
      seemed that males were attempting sexual coercion. There was little evidence,
      however, that this combination of coercion and enticement was successful in
      obtaining copulations. While forced copulation did occur, it was infrequent, and
      no evidence could be found for intimidation. We conclude that harassment is the
      primary form of sexual coercion by male brush-turkeys. Although sexual coercion
      is understood to be a sub-optimal tactic, brush-turkey sexual coercion was
      employed as a primary tactic by dominant males who owned incubation mounds. One
      possible explanation for this apparent paradox is that aggression is the default
      solution for social conflicts in this species, and hence can be interpreted as a
      behavioural syndrome. 

PMID- 24932898
TI  - On evolutionary causes and evolutionary processes.
AB  - In this essay I consider how biologists understand 'causation' and 'evolutionary
      process', drawing attention to some idiosyncrasies in the use of these terms. I
      suggest that research within the evolutionary sciences has been channeled in
      certain directions and not others by scientific conventions, many of which have
      now become counterproductive. These include the views (i) that evolutionary
      processes are restricted to those phenomena that directly change gene
      frequencies, (ii) that understanding the causes of both ecological change and
      ontogeny is beyond the remit of evolutionary biology, and (iii) that biological
      causation can be understood by a dichotomous proximate-ultimate distinction, with
      developmental processes perceived as solely relevant to proximate causation. I
      argue that the notion of evolutionary process needs to be broadened to
      accommodate phenomena such as developmental bias and niche construction that bias
      the course of evolution, but do not directly change gene frequencies, and that
      causation in biological systems is fundamentally reciprocal in nature. This
      article is part of a Special Issue entitled: In Honor of Jerry Hogan.

PMID- 24932895
TI  - Cognitive deficits specific to depression-prone smokers during abstinence.
AB  - Cigarette smoking is associated with a higher prevalence of depressive symptoms
      and individuals with elevated symptoms of depression have more difficulty
      quitting smoking. Depression is accompanied by cognitive deficits similar to
      those observed during nicotine withdrawal. Depressed smokers may smoke to
      alleviate these cognitive symptoms, which are exacerbated upon smoking
      abstinence. We hypothesized that following overnight abstinence, depression-prone
      smokers (DP+; past history and current depression symptoms; n = 34) would exhibit
      deficits in short-term and working memory, and experience greater attentional
      bias for affective stimuli, compared with smokers with no history or current
      symptoms of depression (DP-; n = 34). All participants underwent two laboratory
      sessions, once while smoking abstinent and once while smoking ad libitum (order
      counterbalanced, abstinence biochemically verified). Smokers completed measures
      of short-term memory (STM; word recognition task), working memory (N-back task),
      and attentional bias (Emotional Stroop task). The DP+ group showed declines in
      STM during abstinence compared with smoking, whereas the DP- group did not
      (interaction p = .02). There were small decrements in working memory accuracy
      during abstinence (p = .05), but this did not interact with depression status.
      During the Emotional Stroop task, the DP+ group showed an attentional bias toward
      positive versus neutral stimuli during abstinence compared with smoking
      (interaction p = .01). This study provides initial evidence that depressive
      symptoms may moderate abstinence-induced deficits in STM and shift attentional
      bias toward emotionally salient stimuli during abstinence. These cognitive
      changes may prompt relapse and may help identify novel targets for nicotine
      dependence treatment aimed at attenuating these deficits to improve cessation
      rates.

PMID- 24932900
TI  - A comparison of parotid imaging characteristics and sialendoscopic findings in
      obstructive salivary disorders.
AB  - OBJECTIVES/HYPOTHESIS: To examine how preoperative imaging characteristics
      correlate with sialendoscopic findings and operative outcomes in patients with
      obstructive parotid symptoms. STUDY DESIGN: Retrospective review. METHODS: We
      identified 112 consecutive patients who underwent 134 unilateral or bilateral
      parotid gland sialendoscopies between December 2005 and August 2013. We reviewed
      clinical history, radiographic imaging and reports, operative reports, and
      clinical outcomes. Available preoperative computed tomography (CT) or magnetic
      resonance imaging (MRI) were analyzed for parotid stone size and location
      relative to the masseter muscle. RESULTS: For patients with parotid stone on
      preoperative imaging, at least one stone was found on sialendoscopy in 63% of
      cases. In contrast, for all cases with preoperative imaging negative for stone,
      no stone was found on sialendoscopy suggesting that parotid stones are not
      radiolucent on CT imaging. Furthermore, stones located anterior to the masseter
      were more successfully visualized on sialendoscopy compared to stones located
      posterior to the masseter. Anteriorly located stones were also more accessible
      for endoscopic management, whereas posterior stones required combined approaches
      for management. CONCLUSIONS: Preoperative imaging characteristics such as stone
      presence, size, and location provide essential information that can guide
      surgical planning and clinical outcome expectations for obstructive parotid
      disease management. All parotid CT scans that failed to demonstrate stones on
      imaging had no stone found on sialendoscopy. Stones posterior to the masseter
      muscle are the most difficult to access with sialendoscopy, and in these cases,
      patients should be counseled about the potential need for a transfacial approach
      to remove symptomatic stones. LEVEL OF EVIDENCE: 2b.

PMID- 24932899
TI  - Adaptation of the lateral distal femur DXA scan technique to adults with
      disabilities.
AB  - The technique that best addresses the challenges of assessing bone mineral
      density in children with neuromuscular impairments is a dual-energy X-ray
      absorptiometry (DXA) scan of the lateral distal femur. The purpose of this study
      was to adapt this technique to adults with neuromuscular impairments and to
      assess the reproducibility of these measurements. Thirty-one adults with cerebral
      palsy had both distal femurs scanned twice, with the subject removed and then
      repositioned between each scan (62 distal femurs, 124 scans). Each scan was
      independently analyzed twice by 3 different technologists of varying experience
      with DXA (744 analyses). Precision of duplicate analyses of the same scan was
      good (range: 0.4%-2.3%) and depended on both the specific region of interest and
      the experience of the technologist. Precision was reduced when comparing
      duplicate scans, ranging from 7% in the metaphyseal (cancellous) region to 2.5%
      in the diaphyseal (cortical) region. The least significant change was determined
      as recommended by the International Society for Clinical Densitometry for each
      technologist and each region of interest. Obtaining reliable, reproducible, and
      clinically relevant assessments of bone mineral density in adults with
      neuromuscular impairments can be challenging. The technique of obtaining DXA
      scans of the lateral distal femur can be successfully applied to this population
      but requires a commitment to developing the necessary expertise. 

PMID- 24932901
TI  - Etiopathogenesis of equinovarus foot malformations.
AB  - Congenital talipes equinovarus (CTEV) is the most common musculoskeletal birth
      defect affecting approximately 1/700-1/1000 of liveborns. Even though extensive
      epidemiological and genetic studies have been carried out to address its causes,
      the precise mechanisms leading to this common birth defect remain elusive. CTEV
      is a multifactorial disorder, hence the combination of genetic and environmental
      factors are known contributors to this developmental abnormality. So far a
      handful of genes involved in limb patterning like PITX1, HOXA, HOXD, TBX4, and
      RBM10, as well as genes involved in muscle contraction, have been identified as
      possible players. Among many environmental factors investigated, maternal smoking
      seems to hold the strongest consistent association with this disorder. This
      article will review and discuss some of the most common genetic and environmental
      factors associated with the etiopathogenesis of CTEV. 

PMID- 24932902
TI  - Infantile hydrocephalus: a review of epidemiology, classification and causes.
AB  - Hydrocephalus is a common but complex condition caused by physical or functional
      obstruction of CSF flow that leads to progressive ventricular dilatation. Though
      hydrocephalus was recently estimated to affect 1.1 in 1000 infants, there have
      been few systematic assessments of the causes of hydrocephalus in this age group,
      which makes it a challenging condition to approach as a scientist or as a
      clinician. Here, we review contemporary literature on the epidemiology,
      classification and pathogenesis of infantile hydrocephalus. We describe the major
      environmental and genetic causes of hydrocephalus, with the goal of providing a
      framework to assess infants with hydrocephalus and guide future research. 

PMID- 24932904
TI  - Primary ductal adenocarcinoma of the lacrimal gland, associated with abundant
      intracytoplasmic lumens containing some eosinophilic hyaline globules:
      cytological, histological and ultrastructural findings.
AB  - A primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare distinct
      subtype of an epithelial tumor arising in the lacrimal gland. PDA is the
      counterpart of salivary duct carcinoma (SDC) resembling an invasive ductal
      carcinoma (IDC) of the breast. In our case, PDA revealed histopathological and
      immunohistochemical results corresponding to SDC. Interestingly, the tumor cells
      showed intracytoplasmic vacuoles containing dense eosinophilic hyaline globules
      at light microscopy. Ultrastructurally, the tumor cells exhibited microvilli
      lined intracytoplasmic lumen containing homogenous electron-dense secretory
      products. A previous study demonstrated that numerous intracytoplasmic lumens of
      tumor cells are favored breast malignant tumor, similar to the histopathology of
      PDA, rather than benign lesion. This characteristic finding may be meaningful to
      diagnose high grade epithelial tumors including PDA.

PMID- 24932903
TI  - 15q26.1 microdeletion encompassing only CHD2 and RGMA in two adults with moderate
      intellectual disability, epilepsy and truncal obesity.
AB  - We report two patients with microdeletions in chromosomal subdomain 15q26.1
      encompassing only two genes, CHD2 and RGMA. Both patients present a distinct
      phenotype with intellectual disability, epilepsy, behavioral issues, truncal
      obesity, scoliosis and facial dysmorphism. CHD2 haploinsufficiency is known to
      cause intellectual disability and epilepsy, RGMA haploinsufficiency might explain
      truncal obesity with onset around puberty observed in our two patients. 

PMID- 24932905
TI  - Application of a prediction model for the progression of rheumatoid arthritis in
      patients with undifferentiated arthritis.
AB  - INTRODUCTION: Different prediction rules have been applied to patients with
      undifferentiated arthritis (UA) to identify those that progress to rheumatoid
      arthritis (RA). The Leiden Prediction Rule (LPR) has proven useful in different
      UA cohorts. OBJECTIVE: To apply the LPR to a cohort of patients with UA of
      northeastern Mexico. METHODS: We included 47 patients with UA, LPR was applied at
      baseline. They were evaluated and then classified after one year of follow-up
      into two groups: those who progressed to RA (according to ACR 1987) and those who
      did not. RESULTS: 43% of the AI patients developed RA. In the RA group, 56% of
      patients obtained a score <= 6 and only 15% >= 8. 70% who did not progress to RA
      had a score between 6 and <= 8. There was no difference in median score of LPR
      between groups, p=0.940. CONCLUSION: Most patients who progressed to RA scored
      less than 6 points in the LPR. Unlike what was observed in other cohorts, the
      model in our population did not allow us to predict the progression of the
      disease.

PMID- 24932906
TI  - Macrophage activation syndrome as a severe manifestation of adult's Sitll's
      disease. Hemophagocytic cells in ascites.

PMID- 24932907
TI  - Prosthesis infection by Mycobacterium tuberculosis in a patient with rheumatoid
      arthritis: A case report and literature review.

PMID- 24932908
TI  - Oncogenic fusion proteins expressed in immature hematopoietic cells fail to
      recapitulate the transcriptional changes observed in human AML.
AB  - Reciprocal chromosomal translocations are observed in one-third of acute myeloid
      leukemia (AML) cases. Targeting and understanding the effects of the resulting
      aberrant oncogenic fusion proteins may help developing drugs against specific
      leukemic subtypes, as demonstrated earlier by the use of ATRA in acute
      promyelocytic leukemia. Hematopoietic stem/progenitor (HSPCs) cells transduced
      with oncogenic fusion genes are regarded as promising in vitromodels of their
      corresponding AML subtypes. Here, we critically assessed the potential of such in
      vitro models using an integrative bioinformatics approach. Surprisingly, we found
      that the gene-expression profiles of CD34+ human HSPCs transformed with the
      potent oncogenic fusion proteins AML-ETO or MLL-AF9, only weakly resembled those
      derived from primary AML samples. Hence, our work raises concerns as to the
      relevance of the use of in vitro transduced cells to study the impact of
      transcriptional deregulation in human AML. 

PMID- 24932909
TI  - A model based on environmental factors for diameter distribution in black wattle
      in Brazil.
AB  - This article discusses the dynamics of a diameter distribution in stands of black
      wattle throughout its growth cycle using the Weibull probability density
      function. Moreover, the parameters of this distribution were related to
      environmental variables from meteorological data and surface soil horizon with
      the aim of finding a model for diameter distribution which their coefficients
      were related to the environmental variables. We found that the diameter
      distribution of the stand changes only slightly over time and that the estimators
      of the Weibull function are correlated with various environmental variables, with
      accumulated rainfall foremost among them. Thus, a model was obtained in which the
      estimators of the Weibull function are dependent on rainfall. Such a function can
      have important applications, such as in simulating growth potential in regions
      where historical growth data is lacking, as well as the behavior of the stand
      under different environmental conditions. The model can also be used to project
      growth in diameter, based on the rainfall affecting the forest over a certain
      time period. 

PMID- 24932910
TI  - In response to "Preoperative angiotensin axis blockade therapy, intraoperative
      hypotension, and the risks of postoperative acute kidney injury".

PMID- 24932911
TI  - Gender differences in awareness and outcomes during acute traumatic brain injury
      recovery.
AB  - BACKGROUND: Recent literature on traumatic brain injury (TBI), though mixed when
      reporting outcomes, seems collectively to suggest possible gender advantage for
      women in postinjury recovery, especially in executive functions. Hormonal
      neuroprotection, through female reproductive hormones, is often proposed as an
      underlying factor in these results. We explored potential gender differences in
      an aspect of executive functions, self-awareness (SA), which is often impaired
      after TBI, limits patient effort in critical rehabilitation, and increases
      caregiver burden. METHODS: Within a prospective survey, repeated-measures design,
      121 patients with moderate or severe TBI undergoing acute rehabilitation in a
      Level 1 trauma center, a family member or caregiver informant, and a treating
      clinician were asked to complete the Patient Competency Rating Scale (PCRS) and
      the Frontal Systems Behavior Scale (FrSBe) at admission and discharge. RESULTS:
      Although overall, women and men with TBI showed generally similar levels of SA,
      women had significantly better awareness of their injury-related deficits at
      acute rehabilitation discharge, even when controlling for age, education, and
      injury severity. CONCLUSIONS: Mixed findings in this study mirror the pattern of
      results that dominate the published literature on gender and TBI. Gender
      differences in executive dysfunction may not be as large or robust as some
      researchers argue. In addition, complex interplays of socialization, gender-role
      expectations, naturally occurring male and female ability differences, and
      differences in access to postinjury rehabilitation are understudied potential
      moderators.

PMID- 24932912
TI  - Molecular characterization and analysis of a novel protein disulfide isomerase
      like protein of Eimeria tenella.
AB  - Protein disulfide isomerase (PDI) and PDI-like proteins are members of the
      thioredoxin superfamily. They contain thioredoxin-like domains and catalyze the
      physiological oxidation, reduction and isomerization of protein disulfide bonds,
      which are involved in cell function and development in prokaryotes and
      eukaryotes. In this study, EtPDIL, a novel PDI-like gene of Eimeria tenella, was
      cloned using rapid amplification of cDNA ends (RACE) according to the expressed
      sequence tag (EST). The EtPDIL cDNA contained 1129 nucleotides encoding 216 amino
      acids. The deduced EtPDIL protein belonged to thioredoxin-like superfamily and
      had a single predicted thioredoxin domain with a non-classical thioredoxin-like
      motif (SXXC). BLAST analysis showed that the EtPDIL protein was 55-59% identical
      to PDI-like proteins of other apicomplexan parasites. The transcript and protein
      levels of EtPDIL at different development stages were investigated by real-time
      quantitative PCR and western blot. The messenger RNA and protein levels of EtPDIL
      were higher in sporulated oocysts than in unsporulated oocysts, sporozoites or
      merozoites. Protein expression was barely detectable in unsporulated oocysts.
      Western blots showed that rabbit antiserum against recombinant EtPDIL recognized
      only a native 24 kDa protein from parasites. Immunolocalization with EtPDIL
      antibody showed that EtPDIL had a disperse distribution in the cytoplasm of whole
      sporozoites and merozoites. After sporozoites were incubated in complete medium,
      EtPDIL protein concentrated at the anterior of the sporozoites and appeared on
      the surface of parasites. Specific staining was more intense and mainly located
      on the parasite surface after merozoites released from mature schizonts invaded
      DF-1 cells. After development of parasites in DF-1 cells, staining intensified in
      trophozoites, immature schizonts and mature schizonts. Antibody inhibition of
      EtPDIL function reduced the ability of E. tenella to invade DF-1 cells. These
      results suggested that EtPDIL might be involved in sporulation in external
      environments and in host cell adhesion, invasion and development of E. tenella. 

PMID- 24932913
TI  - Structure-based virtual screening approach for discovery of covalently bound
      ligands.
AB  - We present a fast and effective covalent docking approach suitable for large
      scale virtual screening (VS). We applied this method to four targets (HCV NS3
      protease, Cathepsin K, EGFR, and XPO1) with known crystal structures and known
      covalent inhibitors. We implemented a customized "VS mode" of the Schrodinger
      Covalent Docking algorithm (CovDock), which we refer to as CovDock-VS. Known
      actives and target-specific sets of decoys were docked to selected X-ray
      structures, and poses were filtered based on noncovalent protein-ligand
      interactions known to be important for activity. We were able to retrieve 71%,
      72%, and 77% of the known actives for Cathepsin K, HCV NS3 protease, and EGFR
      within 5% of the decoy library, respectively. With the more challenging XPO1
      target, where no specific interactions with the protein could be used for
      postprocessing of the docking results, we were able to retrieve 95% of the
      actives within 30% of the decoy library and achieved an early enrichment factor
      (EF1%) of 33. The poses of the known actives bound to existing crystal structures
      of 4 targets were predicted with an average RMSD of 1.9 A. To the best of our
      knowledge, CovDock-VS is the first fully automated tool for efficient virtual
      screening of covalent inhibitors. Importantly, CovDock-VS can handle multiple
      chemical reactions within the same library, only requiring a generic SMARTS-based
      predefinition of the reaction. CovDock-VS provides a fast and accurate way of
      differentiating actives from decoys without significantly deteriorating the
      accuracy of the predicted poses for covalent protein-ligand complexes. Therefore,
      we propose CovDock-VS as an efficient structure-based virtual screening method
      for discovery of novel and diverse covalent ligands. 

PMID- 24932915
TI  - VMSbase: an R-package for VMS and logbook data management and analysis in
      fisheries ecology.
AB  - VMSbase is an R package devised to manage, process and visualize information
      about fishing vessels activity (provided by the vessel monitoring system--VMS)
      and catches/landings (as reported in the logbooks). VMSbase is primarily
      conceived to be user-friendly; to this end, a suite of state-of-the-art analyses
      is accessible via a graphical interface. In addition, the package uses a database
      platform allowing large datasets to be stored, managed and processed vey
      efficiently. Methodologies include data cleaning, that is removal of redundant or
      evidently erroneous records, and data enhancing, that is interpolation and
      merging with external data sources. In particular, VMSbase is able to estimate
      sea bottom depth for single VMS pings using an on-line connection to the National
      Oceanic and Atmospheric Administration (NOAA) database. It also allows VMS pings
      to be assigned to whatever geographic partitioning has been selected by users.
      Standard analyses comprise: 1) metier identification (using a modified CLARA
      clustering approach on Logbook data or Artificial Neural Networks on VMS data);
      2) linkage between VMS and Logbook records, with the former organized into
      fishing trips; 3) discrimination between steaming and fishing points; 4)
      computation of spatial effort with respect to user-selected grids; 5) calculation
      of standard fishing effort indicators within Data Collection Framework; 6) a
      variety of mapping tools, including an interface for Google viewer; 7) estimation
      of trawled area. Here we report a sample workflow for the accessory sample
      datasets (available with the package) in order to explore the potentialities of
      VMSbase. In addition, the results of some performance tests on two large datasets
      (1*10(5) and 1*10(6) VMS signals, respectively) are reported to inform about the
      time required for the analyses. The results, although merely illustrative,
      indicate that VMSbase can represent a step forward in extracting and enhancing
      information from VMS/logbook data for fisheries studies.

PMID- 24932914
TI  - Spectroscopic characterization of a green copper site in a single-domain
      cupredoxin.
AB  - Cupredoxins are widespread copper-binding proteins, mainly involved in electron
      transfer pathways. They display a typical rigid greek key motif consisting of an
      eight stranded beta-sandwich. A fascinating feature of cupredoxins is the natural
      diversity of their copper center geometry. These geometry variations give rise to
      drastic changes in their color, such as blue, green, red or purple. Based on
      several spectroscopic and structural analyses, a connection between the geometry
      of their copper-binding site and their color has been proposed. However, little
      is known about the relationship between such diversity of copper center geometry
      in cupredoxins and possible implications for function. This has been difficult to
      assess, as only a few naturally occurring green and red copper sites have been
      described so far. We report herein the spectrocopic characterization of a novel
      kind of single domain cupredoxin of green color, involved in a respiratory
      pathway of the acidophilic organism Acidithiobacillus ferrooxidans. Biochemical
      and spectroscopic characterization coupled to bioinformatics analysis reveal the
      existence of some unusual features for this novel member of the green cupredoxin
      sub-family. This protein has the highest redox potential reported to date for a
      green-type cupredoxin. It has a constrained green copper site insensitive to pH
      or temperature variations. It is a green-type cupredoxin found for the first time
      in a respiratory pathway. These unique properties might be explained by a region
      of unknown function never found in other cupredoxins, and by an unusual length of
      the loop between the second and the fourth copper ligands. These discoveries will
      impact our knowledge on non-engineered green copper sites, whose involvement in
      respiratory chains seems more widespread than initially thought. 

PMID- 24932916
TI  - Expression and functional characterization of NOD2 in decidual stromal cells
      isolated during the first trimester of pregnancy.
AB  - NOD2, one of the cytosolic proteins that contain a nuclear oligomerization domain
      (NOD), is a pattern recognition receptor (PRR) involved in innate immune
      responses to intracellular pathogens. Little is known, however, about the effect
      of NOD2 expression on the maternal-fetal relationship. Our aim was to elucidate
      the functions of NOD2 in normal decidual stromal cells (DSCs) from the first
      trimester. Tissues and DSCs were isolated from 26 patients with normal
      pregnancies that required abortion. The expression of NOD2 in deciduas/decidual
      stromal cells (DSCs) was examined by real-time PCR, immunohistochemistry, and In
      cell western. DSCs containing NOD2 were stimulated by its ligand, muramyl
      dipeptide (MDP). The secretion of various cytokines and chemokines were measured
      by ELISA and the apoptotic rate was determined by flow cytometry. Treatment with
      MDP significantly elevated the expression of both NOD2 mRNA and protein levels in
      DSCs. In addition, MDP activation of NOD2 significantly increased IL-1beta and
      MCP-1 cytokine expression in a dose dependent manner but had no effect on IL-12
      expression. IL-1beta and TNF-alpha also significantly increased the expression of
      NOD2 in DSCs, suggesting a positive feedback loop mechanism. Moreover, MDP
      stimulation augmented DSC apoptosis. In summary, the results suggest that NOD2
      expression in DSCs plays an important role in protecting the embryo and
      preventing infection in the maternal-fetal interface. 

PMID- 24932918
TI  - Regulation of virus-induced inflammatory response by Dunaliella salina alga
      extract in macrophages.
AB  - Previous reports have suggested that many constituents within various algal
      samples are able to attenuate LPS-induced inflammatory effects. To date no report
      has been published on the regulation of virus-induced inflammatory response of
      Dunaliella salina carotenoid extract. In the present study, the anti-inflammatory
      effect of D. salina carotenoid extract on pseudorabies virus (PRV)-infected RAW
      264.7 macrophages was investigated. We evaluated the anti-inflammatory effect of
      D. salina carotenoid extract on PRV-infected RAW 264.7 cells by measuring cell
      viability, cytotoxicity, production of inflammatory mediators such as NO, iNOS,
      COX-2, pro-inflammatory cytokines and anti-virus replication by plaque assay. We
      found down-regulation of the expression of the iNOS, COX-2 and pro-inflammatory
      genes IL-1beta, IL-6, TNF-alpha, and MCP-1 in a dose-dependent manner. Although
      there was no effect on viral replication, there were tendencies toward lower
      virus titer and tendencies toward higher cell survival. Most importantly, we
      found that inhibition of TLR9, PI3K and Akt phosphorylation plays a crucial role
      in the extract-mediated NF-kappaB regulation by modulating IKK-IkappaB signaling
      in PRV-infected RAW264.7 cells. These results indicate that D. salina carotenoid
      extracts inhibited inflammation by inhibition of NF-kappaB activation by TLR9
      dependent via PI3K/Akt inactivation. 

PMID- 24932917
TI  - Variations in the relation between education and cause-specific mortality in 19
      European populations: a test of the "fundamental causes" theory of social
      inequalities in health.
AB  - Link and Phelan have proposed to explain the persistence of health inequalities
      from the fact that socioeconomic status is a "fundamental cause" which embodies
      an array of resources that can be used to avoid disease risks no matter what
      mechanisms are relevant at any given time. To test this theory we compared the
      magnitude of inequalities in mortality between more and less preventable causes
      of death in 19 European populations, and assessed whether inequalities in
      mortality from preventable causes are larger in countries with larger resource
      inequalities. We collected and harmonized mortality data by educational level on
      19 national and regional populations from 16 European countries in the first
      decade of the 21st century. We calculated age-adjusted Relative Risks of
      mortality among men and women aged 30-79 for 24 causes of death, which were
      classified into four groups: amenable to behavior change, amenable to medical
      intervention, amenable to injury prevention, and non-preventable. Although an
      overwhelming majority of Relative Risks indicate higher mortality risks among the
      lower educated, the strength of the education-mortality relation is highly
      variable between causes of death and populations. Inequalities in mortality are
      generally larger for causes amenable to behavior change, medical intervention and
      injury prevention than for non-preventable causes. The contrast between
      preventable and non-preventable causes is large for causes amenable to behavior
      change, but absent for causes amenable to injury prevention among women. The
      contrast between preventable and non-preventable causes is larger in Central &
      Eastern Europe, where resource inequalities are substantial, than in the Nordic
      countries and continental Europe, where resource inequalities are relatively
      small, but they are absent or small in Southern Europe, where resource
      inequalities are also large. In conclusion, our results provide some further
      support for the theory of "fundamental causes". However, the absence of larger
      inequalities for preventable causes in Southern Europe and for injury mortality
      among women indicate that further empirical and theoretical analysis is necessary
      to understand when and why the additional resources that a higher socioeconomic
      status provides, do and do not protect against prevailing health risks. 

PMID- 24932919
TI  - Occurrence and exposure to polycyclic aromatic hydrocarbons in kindling-free
      charcoal grilled meat products in Taiwan.
AB  - This study aimed to determine the contents of 16 PAHs in kindling-free-charcoal
      grilled meat and seafood products by GC-MS coupled with a QuEChERS method, and
      estimate the potential risk associated with consumption of those products in
      Taiwan. Results showed that the total PAHs contents ranged from 6.3+/-0.9 to
      238.8+/-8.3 ng/g in poultry meat, 0.1+/-0.0-547.5+/-12.2 ng/g in red meat, and
      6.6+/-1.4-249.7+/-6.4 ng/g in seafood products. Among various PAHs, the highly
      carcinogenic benzo[a]pyrene was detected in chicken breast grilled at 84 degrees
      C (30 min), chicken heart at 100 degrees C (26 min), chicken drumstick at 74
      degrees C (20 min), duck drumstick at 85 degrees C (40 min), and lamb steak at 88
      degrees C (12 min), with its level amounting to 1.3+/-0.0, 2.4+/-0.1, 4.0+/-1.3,
      3.1+/-0.0, and 5.8+/-0.5 ng/g, respectively. The generation of PAHs was
      associated with grilling time, temperature and fat content. Risk assessment of
      dietary exposure to PAHs revealed toxicity equivalent to range from ND - 6.174+/
      0.505 MUg/g and margin of exposure was >10,000, which agreed with the EFSA's
      definition of low public health concern. The lifelong average daily PAHs intake
      was higher for adults than for elderly people in Taiwan, however, consumption of
      kindling-free-charcoal grilled meat should not be a public health concern based
      on cancer risk potency.

PMID- 24932920
TI  - Does dietary L-methionine serve as a foe or friend for global DNA
      hypomethylation?

PMID- 24932921
TI  - Neurofibromin deficiency-associated transcriptional dysregulation suggests a
      novel therapy for tibial pseudoarthrosis in NF1.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by
      mutations in NF1. Among the earliest manifestations is tibial pseudoarthrosis and
      persistent nonunion after fracture. To further understand the pathogenesis of
      pseudoarthrosis and the underlying bone remodeling defect, pseudoarthrosis tissue
      and cells cultured from surgically resected pseudoarthrosis tissue from NF1
      individuals were analyzed using whole-exome and whole-transcriptome sequencing as
      well as genomewide microarray analysis. Genomewide analysis identified multiple
      genetic mechanisms resulting in somatic biallelic NF1 inactivation; no other
      genes with recurring somatic mutations were identified. Gene expression profiling
      identified dysregulated pathways associated with neurofibromin deficiency,
      including phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase
      (MAPK) signaling pathways. Unlike aggressive NF1-associated malignancies, tibial
      pseudoarthrosis tissue does not harbor a high frequency of somatic mutations in
      oncogenes or other tumor-suppressor genes, such as p53. However, gene expression
      profiling indicates that pseudoarthrosis tissue has a tumor-promoting
      transcriptional pattern, despite lacking tumorigenic somatic mutations.
      Significant overexpression of specific cancer-associated genes in pseudoarthrosis
      highlights a potential for receptor tyrosine kinase inhibitors to target
      neurofibromin-deficient pseudoarthrosis and promote proper bone remodeling and
      fracture healing.

PMID- 24932922
TI  - RNA interference-mediated knockdown of three putative aminopeptidases N affects
      susceptibility of Spodoptera exigua larvae to Bacillus thuringiensis Cry1Ca.
AB  - Aminopeptidase N (APN) isoforms in insects have been documented to be involved in
      the mode of action of insecticidal crystal proteins (Cry) from Bacillus
      thuringiensis. Here we cloned two novel Seapns from the larval midgut of
      Spodoptera exigua, a major pest of many crops of economic importance in China.
      According to a phylogenetic analysis, these two novel SeAPNs, along with the four
      SeAPN isoforms already described, belong to six different clades. All the six
      SeAPNs share similar structural features. From N- to C-terminus a signal peptide,
      a gluzincin aminopeptidase motif, a zinc binding/gluzincin motif, and a
      glycosylphosphatidylinositol-anchor sequence are located. The six Seapn genes
      were highly expressed at the larval stage, especially in the larval gut.
      Ingestion during four consecutive days of double-stranded RNAs (dsRNAs) targeting
      Seapn1, Seapn2, Seapn3, Seapn4, Seapn5 and Seapn6 significantly reduced
      corresponding mRNA levels by 55.6%, 45.5%, 43.2%, 56.8%, 45.4%, and 46.0%
      respectively, compared with those recorded in control larvae fed on non-specific
      dsRNA (dsegfp). When the larvae that previously ingested phosphate buffered
      saline (PBS)-, dsegfp-, or six dsSeapns-overlaid diets were then exposed to a
      diet containing Cry1Ca, the larval mortalities were 71.2%, 69.3%, 52.0%, 77.2%,
      43.3%, 62.0%, 65.4% and 53.8% respectively recorded after 6days. ANOVA analysis
      revealed that the larvae previously fed on dsSeapn1-, dsSeapn3-, and dsSeapn6
      overlaid diets had significantly lower mortalities than those previously ingested
      PBS-, dsegfp-, dsSeapn2-, dsSeapn4- and dsSeapn5-overlaid diets. Thus, these
      results suggest that SeAPN1, SeAPN3 and SeAPN6 may be candidate receptors for
      Cry1Ca in S. exigua. 

PMID- 24932925
TI  - Characterization of a conical intersection in a charge-transfer dimer with two
      dimensional time-resolved stimulated Raman spectroscopy.
AB  - Photochemical reactions are mediated by conical intersections (CI), which are
      difficult to directly probe and characterize. To gain insight into CIs, two
      dimensional femtosecond stimulated Raman spectroscopy (2D-FSRS) is used to
      examine a model excited-state charge-transfer (CT) complex consisting of an
      electron donor, tetramethylbenzene (TMB), and an acceptor,
      tetracyanoquinodimethane (TCNQ). Following impulsive excitation, the excited
      state transient absorption reveals large-amplitude excited-state wave packet
      motion along low-frequency modes, in particular TCNQ's totally symmetric 323 cm(
      1) CCN bend, which persist for ~5 ps. These low-frequency coherences modulate the
      intensity and peak frequencies of the excited-state FSRS vibrational spectra. In
      particular, large-magnitude oscillations at 323 cm(-1) are observed in the peak
      frequency (Deltaomega = 2 cm(-1)) and intensity (DeltaOD = 1.5 mOD) of the
      nontotally symmetric 1271 cm(-1) C?C rocking mode. The magnitude of these
      oscillations is analyzed to determine the first-order anharmonic coupling between
      the high- and low-frequency degrees of freedom in the excited state. The
      anharmonic coupling between the totally symmetric 323 cm(-1) and the nontotally
      symmetric 1271 cm(-1) modes is estimated to be in excess of 50 cm(-1), strongly
      suggesting that they are the tuning and coupling modes, respectively, for the CI
      that connects the CT excited state to the neutral ground state and controls
      charge recombination internal conversion. 

PMID- 24932923
TI  - Accelerator mass spectrometry detection of beryllium ions in the antigen
      processing and presentation pathway.
AB  - Exposure to small amounts of beryllium (Be) can result in beryllium sensitization
      and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is
      presented to Be-responsive T-cells by professional antigen-presenting cells
      (APC). This presentation drives T-cell proliferation and pro-inflammatory
      cytokine (IL-2, TNFalpha, and IFNgamma) production and leads to granuloma
      formation. The mechanism by which beryllium enters an APC and is processed to
      become part of the beryllium antigen complex has not yet been elucidated.
      Developing techniques for beryllium detection with enough sensitivity has
      presented a barrier to further investigation. The objective of this study was to
      demonstrate that Accelerator Mass Spectrometry (AMS) is sensitive enough to
      quantify the amount of beryllium presented by APC to stimulate Be-responsive T
      cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T
      cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of
      beryllium processed for presentation was determined. Further, IFNgamma
      intracellular cytokine assays were performed to demonstrate that Be-ferritin (at
      levels used in the experiments) could stimulate Be-responsive T-cells when
      presented by an APC of the correct HLA type (HLA-DP0201). The results indicated
      that Be-responsive T-cells expressed IFNgamma only when APC with the correct HLA
      type were able to process Be for presentation. Utilizing AMS, it was determined
      that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and
      APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA
      DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng)
      than HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection
      of picogram levels of Be processed by APC is possible. Further, regardless of
      form, Be requires processing by APC to successfully stimulate Be-responsive T
      cells to generate IFNgamma.

PMID- 24932924
TI  - Genetic manipulation of outer membrane permeability: generating porous
      heterogeneous catalyst analogs in Escherichia coli.
AB  - The limited permeability of the E. coli outer membrane can significantly hinder
      whole-cell biocatalyst performance. In this study, the SARS coronavirus small
      envelope protein (SCVE) was expressed in E. coli cells previously engineered for
      periplasmic expression of carbonic anhydrase (CA) activity. This maneuver
      increased small molecule uptake by the cells, resulting in increased apparent CA
      activity of the biocatalysts. The enhancements in activity were quantified using
      methods developed for traditional heterogeneous catalysis. The expression of the
      SCVE protein was found to significantly reduce the Thiele moduli (phi), as well
      as increase the effectiveness factors (eta), effective diffusivities (De), and
      permeabilities (P) of the biocatalysts. These catalytic improvements translated
      into superior performance of the biocatalysts for the precipitation of calcium
      carbonate from solution which is an attractive strategy for long-term
      sequestration of captured carbon dioxide. Overall, these results demonstrate that
      synthetic biology approaches can be used to enhance heterogeneous catalysts
      incorporated into microbial whole-cell scaffolds. 

PMID- 24932926
TI  - Less than 1000 days to go for MDGs 4 and 5: where are we and what needs to be
      done?

PMID- 24932927
TI  - Reducing the burden of maternal and child morbidity and mortality in the Eastern
      Mediterranean Region? Yes, we can.
AB  - Maternal and child morbidity and mortality are a major public health, development
      and human rights challenge globally and in the WHO Eastern Mediterranean Region.
      The Region is diverse, with high-, middle- and low- income countries, many
      suffering from political instability, conflicts and other complex development
      challenges. Although progress has been made towards Millennium Development Goals
      4 and 5, it has been uneven both between and within countries. This paper makes
      an analysis of the strengths, weaknesses, opportunities and threats to improving
      maternal and child mortality and morbidity with a focus on the Region. In answer
      to the question whether we can reduce the burden of maternal and child morbidity
      and mortality in the Region: yes, we can. However, commitment and collaboration
      are needed at the country, regional and international levels. 

PMID- 24932928
TI  - Community participation eludes Pakistan's maternal, newborn and child health
      programme.
AB  - This study looked at the comprehensiveness of the primary health care approach
      being applied in Pakistan's National Maternal, Newborn and Child Health (MNCH)
      Programme launched in 2005. The methods included a review of the programme's
      guideline documents, in-depth interviews with managers/advisors and focus group
      discussions with community groups and service providers. The MNCH Programme is
      applying a selective primary care model. Programme advisors and managers were
      concerned about the quality of training, political interference and incomplete
      implementation. Service providers were not working together as envisioned.
      Community midwives complained about the community's perceptions of them.
      Community members were unaware of MNCH Programme implementation in their areas.
      Pakistan's primary health care programme needs to be reviewed and revised
      according current thinking on community participation and inter-sectoral
      collaboration to accelerate progress towards achievement of Millennium
      Development Goals 4 and 5. 

PMID- 24932929
TI  - Expanding the comprehensive national neonatal screening programme in the United
      Arab Emirates from 1995 to 2011.
AB  - The national neonatal screening programme in the United Arab Emirates currently
      includes 16 disorders: congenital hypothyroidism, sickle-cell diseases,
      congenital adrenal hyperplasia, biotinidase deficiency and 12 amino acid, organic
      acid and fatty acid disorders. This paper reports data since the programme
      started in January 1995 up to December 2011 on the incidence of screened
      disorders and the molecular basis of positive screened cases. Screening used a
      combination of tandem mass spectrometry, molecular technologies and biochemical
      analysis. A total of 750 365 infants were screened and 717 babies saved from
      associated morbidity and/or mortality. The incidence of screened disorders were
      1:1 873 for congenital hypothyroidism, 1:14 544 for phenylketonuria, 1:3 526 for
      amino acid, organic acid and fatty acid disorders, 1:9 030 for classical
      congenital adrenal hyperplasia, 1:8 300 for biotinidase deficiency, 1:2 384 for
      sickle-cell disease and 1:121 for sickle-cell traits. Coverage of neonatal
      screening in the population reached 95% in 2010. 

PMID- 24932930
TI  - Prevalence and factors associated with exclusive breastfeeding at 6 months of
      life in Tehran: a population-based study.
AB  - Exclusive breastfeeding is the best form of nutrition for infants in the first 6
      months of life. The aim of this study was to determine the prevalence of
      exclusive breastfeeding in Tehran, Islamic Republic of Iran in the first 6 months
      of life, and the factors that influence it. In a population-based, cross
      sectional study 538 mothers with children aged 6-24 months completed an interview
      questionnaire. Only 46.5% of mothers exclusively breastfed their infant in the
      first 6 months of life. In multivariate analysis formula supplementation in the
      hospital (OR = 0.41, 95% CI: 0.17-0.95) and mother receiving conflicting infant
      feeding advice (OR = 0.53, 95% CI: 0.37-0.78) had a negative effect on exclusive
      breastfeeding. Mother's intention to exclusively breastfeed (OR = 5.85, 95% CI:
      2.88-11.9) and infant having first breast contact 6-30 minutes after delivery (OR
      = 2.35, 95% CI: 1.17-4.72) had positive effects on exclusive breastfeeding. 

PMID- 24932931
TI  - Prevalence of anaemia in preschool children in Karma Albalad area, Northern
      State, Sudan.
AB  - Anaemia is a major childhood health problem in developing countries. The aim of
      this cross-sectional study was to determine the prevalence of anaemia, and some
      of its determinants, in preschool children in a rural village in the Northern
      State of Sudan. All children aged 3-6 years attending the 4 village kindergartens
      on the day of the study were enrolled. Demographic and socioeconomic data were
      collected using a questionnaire completed by parents, and blood samples were
      taken for haemoglobin measurement. Out of 163 children, 131 had anaemia
      (haemoglobin level < 11 g/dL), a prevalence of 80.4%. This figure is comparable
      to data from other developing countries. The prevalence of anaemia was not
      significantly associated with any of the studied demographic and socioeconomic
      factors (sex, economic status of the family, mother's literacy or family size) or
      health of the child (history of pica or number of attacks of malaria in the last
      year). A campaign to tackle this serious health issue is urgently needed. 

PMID- 24932932
TI  - Association between dietary habits and body mass index of adolescent females in
      intermediate schools in Riyadh, Saudi Arabia.
AB  - Obesity among Saudi youth is a growing public health challenge. This cross
      sectional study measured body mass index (BMI) and determined the eating habits
      and lifestyle of 107 randomly selected female adolescent students (age 12-15
      years) at schools in Riyadh. The students' heights and weights were measured and
      a pre-tested questionnaire was used to collect data on diet and lifestyle. The
      majority of the students' families had monthly income > 10 000 riyals (US$ 1 =
      3.75 riyals). About half the students (53.3%) were within normal weight, 28.6%
      were underweight, 12.4% overweight and 5.7% obese. The majority of the students
      did not have healthy dietary or exercise habits. There were no significant
      differences between BMI category and dietary pattern and lifestyle. Increasing
      educational programmes with healthy dietary concepts to improve the dietary
      pattern of female adolescents is recommended. 

PMID- 24932933
TI  - Comparison of two assays in the diagnosis of toxoplasmosis: immunological and
      molecular.
AB  - Serological tests for Toxoplasma gondii are inadequate because antibody
      production either fails or is significantly delayed. This study in eastern Iraq
      investigated the IgG-avidity ELISA test for detecting recent T. gondii infections
      among pregnant women and compared immunological methods and PCR as molecular
      assays in the diagnosis of T. gondii. Serums samples were taken from 130 pregnant
      women at risk of toxoplasmosis and a control group of 25 women with normal
      pregnancy. Of 50 IgM- and/or IgG-positive samples, only 15 showed low IgG-avidity
      antibodies. PCR was performed on 25 selected samples. Toxoplasma DNA was detected
      in 15/15 IgM-positive with low IgG-avidity and 1/3 IgM-positive with high IgG
      avidity. None of the IgM-negative with high IgG-avidity showed any Toxoplasma
      DNA. ELISA IgG-avidity when used in combination with ELISA IgG/IgM is a valuable
      assay for the exclusion of ongoing or recently acquired T. gondii infection in
      pregnant women. 

PMID- 24932934
TI  - Prevalence of coeliac disease among adult patients with autoimmune hypothyroidism
      in Jordan.
AB  - The prevalence of coeliac disease among patients with autoimmune hypothyroidism
      has not been studied before in Jordan and other Arab countries. A cross-sectional
      record-based review was made of all adult autoimmune hypothyroidism patients who
      attended a referral centre in Jordan, during an 8-month period. Coeliac disease
      in these patients was diagnosed by the attending physician based on positive
      serological tests for anti-endomysial antibodies IgA and IgG followed by duodenal
      biopsy to confirm the diagnosis of coeliac disease. Of 914 patients recruited,
      117 (12.8%) were seropositive for coeliac disease. Of 87 seropositive patients
      who underwent duodenal biopsy, 39 had positive histological findings of coeliac
      disease (44.8%). Extrapolating from these findings the overall rate of coeliac
      disease among autoimmune hypothyroidism patients was estimated to be 5.7%. In
      multivariate logistic regression coeliac disease was significantly associated
      with older age (> 40 years), presence of other autoimmune diseases, vitamin B12
      deficiency and anaemia. 

PMID- 24932935
TI  - Physicians' knowledge, attitude and practices regarding management of medications
      in Ramadan.
AB  - To evaluate knowledge, attitude and practices (KAP) of physicians regarding the
      management of medications in Ramadan we used a self-administered questionnaire on
      a target sample of 381 physicians at Jordan University Hospital, King Abdulla
      University Hospital and a number of private clinics in Amman, during September
      and October of 2008. A total of 297 questionnaires were returned. Physicians' KAP
      about management of medications in Ramadan was generally insufficient. The main
      factors that affected KAP were age, nationality, specialty, and country and year
      of last qualification (P < 0.05). Female physicians scored better than males, and
      fellows scored better than other groups for knowledge. Most physicians' attitudes
      and practices were in line with religious opinion in regard to which routes of
      drug administration can nullify fasting, indicating that physicians have adequate
      knowledge in this area. 

PMID- 24932936
TI  - Termination of second and early third trimester pregnancy: comparison of 3
      methods.

PMID- 24932937
TI  - Human mitochondrial DNA and endogenous bacterial surrogates for risk assessment
      of graywater reuse.
AB  - Previous graywater risk assessment studies have focused on fecal contamination,
      yet the low density of fecal indicators may not provide the most useful approach
      to assess pathogen removal during graywater treatment. In this study, we employed
      high throughput bacterial sequencing and qPCR to elucidate potential microbial
      surrogates in wastewater sourced from an industrial laundry. In addition, we
      explored human mitochondrial DNA (HmtDNA) as a new, potentially more reliable
      molecular marker, because it can be unambiguously sourced, has a high copy number
      per cell, and is persistent when released from cells with no self-replication in
      graywater. Pyrosequencing and qPCR revealed that laundry water microbiota was
      dominated by the skin-associated bacteria Staphylococcus, Corynebacterium, and
      Propionibacterium (6.5, 5.7, 5.4 log10 copies/100 mL, respectively). While HmtDNA
      was less abundant (2.8 log10 copies/100 mL), it showed a strong positive
      correlation with the opportunistic pathogen Staphylococcus aureus (r=0.54,
      P=3.2*10(-4)) and closely followed a first-order exponential decay model
      (R2=0.98), remaining detectable in stored laundry graywater for up to 6 days at
      20  degrees C. Based on abundance and persistence, we propose HmtDNA and total
      Staphylococcus as future laundry graywater treatment surrogates to potentially
      assess a wide dynamic range of pathogen removal.

PMID- 24932938
TI  - Editorial overview: viral pathogenesis: dealing with complexity in virus-induced
      disease.

PMID- 24932940
TI  - Comparative analysis of antioxidant activity and functional components of the
      ethanol extract of lotus (Nelumbo nucifera) from various growing regions.
AB  - The variations in antioxidant activity and concentration of functional components
      in the ethanol extracts of lotus seeds and rhizomes based on the growing region
      and dryness were investigated. Free radical scavenging activity, total phenolic
      and flavonoid content, and concentration of several specific flavonoids and
      alkaloids in the ethanol extracts of lotus were measured. Antioxidant activity
      and its correlative total phenolic content varied characteristically depending on
      the growing region and dryness. High-perfomance liquid chromatography analysis
      showed that the ethanol extracts of lotus seeds from Vietnam (Ho Chi Minh City),
      raw rhizomes from Korea (Siheung), and dried rhizomes from Japan (Nigata) had the
      greatest specific flavonoid content. The ethanol extracts of seeds from China
      (Hubei), raw rhizomes from Japan (Nigata), and dried rhizomes from Korea
      (Siheung) had the greatest specific alkaloid content. Astragaline, rutin,
      isoquercetin, nuciferine, dauricine, isoliensinine, and neferine were identified
      in lotus rhizomes for the first time in this study. 

PMID- 24932939
TI  - Maternal choline supplementation improves spatial mapping and increases basal
      forebrain cholinergic neuron number and size in aged Ts65Dn mice.
AB  - Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of
      Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic
      neuron (BFCN) degeneration. The present study tested the hypothesis that maternal
      choline supplementation (MCS) improves spatial mapping and protects against BFCN
      degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and
      lactation, dams were assigned to either a choline sufficient (1.1g/kg choline
      chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and
      17months of age, offspring were tested in the radial arm water maze (RAWM) to
      examine spatial mapping followed by unbiased quantitative morphometry of BFCNs.
      Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative
      to normal disomic (2N) littermates. Additionally, a significantly lower number
      and density of medial septum (MS) hippocampal projection BFCNs was also found in
      unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping
      and increased number, density, and size of MS BFCNs in Ts65Dn offspring.
      Moreover, the density and number of MS BFCNs correlated significantly with
      spatial memory proficiency, providing support for a functional relationship
      between these behavioral and morphometric effects of MCS for trisomic offspring.
      Thus, increasing maternal choline intake during pregnancy may represent a safe
      and effective treatment approach for expectant mothers carrying a DS fetus, as
      well as a possible means of BFCN neuroprotection during aging for the population
      at large. 

PMID- 24932941
TI  - Rhinorrhea in Parkinson's disease: a consecutive multicenter study in Japan.
AB  - Recent reports suggest that rhinorrhea, defined as the presence of a runny nose
      unrelated to respiratory infections, allergies, or sinus problems, occurs more
      frequently among patients with Parkinson's disease (PD) than among healthy
      controls. We conducted a questionnaire survey in a multicenter study throughout
      Japan and compared the frequency of rhinorrhea between 231 PD and 187 normal
      control (NC) subjects. After excluding patients with rhinitis or paranasal
      sinusitis, a total of 159 PD and 59 NC subjects were included in our analysis.
      Rhinorrhea occurred more frequently in PD patients than NC subjects (33.3% vs.
      11.9%; P=0.01). Among PD patients, rhinorrhea was more common in men than women
      (P=0.005). Rhinorrhea was not correlated with disease duration, modified Hoehn
      and Yahr score, disease type (akinesia rigidity vs. tremor dominant), or cardiac
      sympathetic function (evaluated by (123)I-metaiodobenzylguanidine uptake). To our
      knowledge, this is the first multicenter study on the frequency of PD-related
      rhinorrhea in Asian countries. 

PMID- 24932943
TI  - When couples disconnect: rumination and withdrawal as maladaptive responses to
      everyday stress.
AB  - Previous research has highlighted the importance of examining the interpersonal
      context of stress and coping. How individuals in a relationship respond to one
      another and cope with stress together have important outcomes on both individual
      and dyadic levels. The current study sought to examine 2 deleterious coping
      responses, rumination and interpersonal withdrawal, as they relate to
      occupational stress and interact in the home setting. An intensive longitudinal
      design was employed in a sample of 87 couples in which 1 partner was working as a
      paramedic. Over a period of 4 consecutive work shifts, daily reports of marital
      tension, spouses' withdrawal, and paramedics' work stress, burnout, and
      rumination were collected. Multilevel models incorporating actor and partner
      effects examined daily associations. Supporting our first and second hypotheses,
      significant associations were observed between paramedics' work stress and
      subsequent rumination and withdrawal on the part of paramedics. Paramedics' work
      related burnout also predicted increased withdrawal from their respective
      spouses. Regarding the role of these coping responses in daily marital
      functioning, paramedics' rumination and spouses' withdrawal were associated with
      increased marital tension over the 4-day period. On days when spouses withdrew
      more from the relationship, the associations between paramedics' rumination and
      both partners' reports of marital tension were greater, supporting our third
      hypothesis. These findings illustrate the importance of examining both partners'
      coping responses as they interact to predict marital tension. They further
      underscore the maladaptive nature of rumination and withdrawal specifically in an
      interpersonal context. Potential implications for collaborative coping are
      discussed. (

PMID- 24932944
TI  - Phosphine-olefin ligands based on a planar-chiral (pi-arene)chromium scaffold:
      design, synthesis, and application in asymmetric catalysis.
AB  - The NMR and X-ray crystallographic studies clarified that planar-chiral
      alkenylene-bridged (phosphino-pi-arene)(phosphine)chromium complexes 3 were
      capable of coordinating to a rhodium(I) cation in a bidentate fashion at the (pi
      arene)-bound phosphorus atom and at the olefin moiety. The P-olefin chelate
      coordination of 3 constructs the effective chiral environment at the metal
      center, and thus, these rhodium complexes display high performances in various
      rhodium-catalyzed asymmetric 1,4- and 1,2-addition reactions with arylboron
      nucleophiles. The control experiments demonstrated that the (eta(2)-olefin)-Rh
      interaction as well as the bridging structure in 3 played the pivotal roles in
      the high enantioselectivity of the Rh-catalyzed asymmetric reactions. To enhance
      the synthetic utilities of these phosphine-olefin ligands, an enantiospecific and
      scalable synthetic method was developed. The novel synthetic method is flexible
      in terms of the substituent variation, and a library of the planar-chiral
      (arene)chromium-based phosphine-olefin ligands was established by the
      combinatorial approach. Among the newly prepared ligand library, compound 3g,
      which is with a bis(3,5-dimethylphenyl)phosphino group on the eta(6)-arene ring,
      was found to be a far better chiral ligand in the rhodium-catalyzed asymmetric
      reactions showing excellent enantioselectivity and high yields. 

PMID- 24932942
TI  - Gender minority stress, mental health, and relationship quality: a dyadic
      investigation of transgender women and their cisgender male partners.
AB  - Research has demonstrated associations between experiences of discrimination,
      relationship quality, and mental health. However, critical questions remain
      unanswered with regard to how stigma enacted and experienced at the dyadic-level
      influences relationship quality and mental health for transgender women and their
      cisgender (nontransgender) male partners. The present study sought to examine how
      experiences of transgender-related discrimination (i.e., unfair treatment,
      harassment) and relationship stigma (i.e., the real or anticipated fear of
      rejection based on one's romantic affiliation) were associated with both partners
      relationship quality and mental health. Couples (n = 191) were recruited to
      participate in cross-sectional survey. Dyadic analyses using actor-partner
      interdependence models were conducted to examine the influence of minority
      stressors on clinically significant depressive distress and relationship quality.
      For both partners, financial hardship, discrimination, and relationship stigma
      were associated with an increased odds of depressive distress. For both partners,
      financial hardship was associated with lower relationship quality. Among
      transgender women, their own and their partner's higher relationship stigma
      scores were associated with lower relationship quality; however, among male
      partners, only their partner's greater relationship stigma scores were associated
      with lower relationship quality. Findings provide preliminary support for dyadic
      crossover effects of relationship stigma on the health of partners. Findings
      illustrate the importance of minority stress and dyadic stress frameworks in
      understanding and intervening upon mental health disparities among transgender
      women and their male partners. Couples-based interventions and treatment
      approaches to help transgender women and their male partners cope with minority
      stressors are warranted to improve the health and well-being of both partners.

PMID- 24932946
TI  - Fruits, berries, and nuts: phytochemicals in wound healing.

PMID- 24932949
TI  - Was your work bundled into the skilled nursing facility payment?

PMID- 24932950
TI  - Cancers mimicking fungal infections.
AB  - Primary and metastatic malignancies may occasionally mimic or coexist with
      cutaneous fungal infections. The authors report 3 cases of cancers that were
      initially presumed to be cutaneous fungal infections. Dermatologists should
      maintain a low threshold for skin biopsy in patients with persistent or
      refractory fungal infections.

PMID- 24932945
TI  - Hair drug testing results and self-reported drug use among primary care patients
      with moderate-risk illicit drug use.
AB  - BACKGROUND: This study sought to examine the utility of hair testing as a
      research measure of drug use among individuals with moderate-risk drug use based
      on the internationally validated Alcohol, Smoking, and Substance Involvement
      Screening Test (ASSIST). METHODS: This study is a secondary analysis using
      baseline data from a randomized trial of brief intervention for drug misuse, in
      which 360 adults with moderate-risk drug use were recruited from two community
      clinics in New Mexico, USA. The current study compared self-reported drug use on
      the ASSIST with laboratory analysis of hair samples using a standard commercially
      available 5-panel test with assay screening and gas chromatography/mass
      spectrometry (GC/MS) confirmation. Both self-report and hair testing covered a 3
      month period. RESULTS: Overall concordance between hair testing and self-report
      was 57.5% (marijuana), 86.5% (cocaine), 85.8% (amphetamines), and 74.3%
      (opioids). Specificity of hair testing at standard laboratory cut-offs exceeded
      90% for all drugs, but sensitivity of hair testing relative to self-report was
      low, identifying only 52.3% (127/243) of self-disclosed marijuana users, 65.2%
      (30/46) of cocaine users, 24.2% (8/33) of amphetamine users, and 2.9% (2/68) of
      opioid users. Among participants who disclosed using marijuana or cocaine in the
      past 3 months, participants with a negative hair test tended to report lower
      frequency use of those drugs (p<.001 for marijuana and cocaine). CONCLUSIONS:
      Hair testing can be useful in studies with moderate-risk drug users, but the
      potential for under-identification of low-frequency use suggests that researchers
      should consider employing low detection cut-offs and using hair testing in
      conjunction with self-report.

PMID- 24932951
TI  - Diabetic foot ulcer off-loading: The gap between evidence and practice. Data from
      the US Wound Registry.
AB  - OBJECTIVE: To evaluate the practice of off-loading diabetic foot ulcers (DFUs)
      using real-world data from a large wound registry to better identify and
      understand the gap between evidence and practice. DESIGN: Retrospective,
      deidentified data were extracted from the US Wound Registry based on
      patient/wound characteristics, procedures performed, and at which clinic the DFU
      was treated. SETTING: 96 clinics (23 from the United States and Puerto Rico)
      PATIENTS: : 11,784 patients; 25,114 DFUs MAIN OUTCOME MEASURES: : Healed/not
      healed, amputated, percent off-loading, percent use of total contact casting
      (TCC), infection rate MAIN RESULTS: : Off-loading was documented in only 2.2% of
      221,192 visits from January 2, 2007, to January 6, 2013. The most common off
      loading option was the postoperative shoe (36.8%) and TCC (16.0%). There were
      significantly more amputations within 1 year for non-TCC-treated DFUs compared
      with TCC-treated DFUs (5.2% vs 2.2%; P = .001). The proportion of healed wounds
      was slightly higher for TCC-treated DFUs versus non-TCC-treated DFUs (39.4% vs
      37.2%). Infection rates were significantly higher for non-TCC-treated DFUs
      compared with TCC-treated DFUs (2.6 vs 1.6; P = 2.1 * 10). Only 59 clinics used
      TCC (61%); 57% of those clinics used traditional TCC, followed by TCC-EZ (36%).
      Among clinics using any type of TCC, 96.3% of the DFUs that did not receive TCC
      were "TCC-eligible" ulcers. Among clinics using "traditional" TCC systems, 1.4%
      of DFUs were treated with TCC, whereas clinics using TCC-EZ provided TCC to 6.2%
      of DFUs. CONCLUSION: Total contact casting is vastly underutilized in DFU wound
      care settings, suggesting that there is a gap in practice for adequate off
      loading. New, easier-to-apply TCC kits, such as the TCC-EZ, may increase the
      frequency with which this ideal form of adequate off-loading is utilized.

PMID- 24932952
TI  - Healing effect of sea buckthorn, olive oil, and their mixture on full-thickness
      burn wounds.
AB  - OBJECTIVE: The purpose of this study is to evaluate the healing effect of silver
      sulfadiazine (SSD), sea buckthorn, olive oil, and 5% sea buckthorn and olive oil
      mixture on full-thickness burn wounds with respect to both gross and
      histopathologic features. METHODS: Full-thickness burns were induced on 60 rats;
      the rats were then were divided into 5 groups and treated with sea buckthorn,
      olive oil, a 5% sea buckthorn/olive oil mixture, SSD, and normal saline
      (control). They were observed for 28 days, and the wounds' healing process was
      evaluated. RESULTS: Wound contraction occurred faster in sea buckthorn, olive
      oil, and the sea buckthorn/olive oil mixture groups compared with the SSD and
      control groups. The volume of the exudates was controlled more effectively in
      wounds treated with the sea buckthorn/olive oil mixture. Purulent exudates were
      observed in the control group, but the others did not show infection. The group
      treated with sea buckthorn/olive oil mixture revealed more developed re
      epithelialization with continuous basement membrane with a mature granulation
      tissue, whereas the SSD-treated group showed ulceration, necrosis, and immature
      granulation. The results show that sea buckthorn and olive oil individually are
      proper dressing for burn wounds and that they also show a synergetic effect when
      they are used together. CONCLUSION: A sea buckthorn and olive oil mixture could
      be considered as an alternative dressing for full-thickness burns because of
      improved wound healing characteristics and antibacterial property.

PMID- 24932953
TI  - A novel technique for increasing skin oxygenation.
AB  - OBJECTIVE: To develop a novel technique for increasing skin oxygenation based on
      diffusion principles and Fick's laws of diffusion. METHODS: A device that allows
      the creation of an oxygen-depleted environment immediately to the skin while
      simultaneously allowing measurement of the transcutaneous oxygen tension (TcPo2)
      levels was created. This device forms an oxygen gradient from the capillary bed
      of the subcutaneous tissue, through the skin's semipermeable membrane, and toward
      the oxygen-depleted enclosed environment. A healthy adult subject was fitted with
      the device. Once baseline TcPo2 levels were recorded, the oxygen concentration
      within the device was lowered, and TcPo2 levels were monitored. Effects were also
      studied when subjects breathed 100% oxygen for 5 minutes. RESULTS: Oxygen levels
      in the device decreased in accordance with increases in skin TcPo2 levels
      measured within the device. CONCLUSIONS: The application of this technique
      results in an increase in oxygen concentration in the skin and subcutaneous
      tissue in healthy subjects with normal, well-perfused skin. Whether this novel
      technique produces an increase in the skin oxygenation of subjects with
      inappropriate tissue oxygenation and chronic wounds requires further study.

PMID- 24932954
TI  - Topical phytochemicals: applications for wound healing.
AB  - To maximize the effectiveness of any complementary therapy in treating chronic
      wounds, the clinician must fully appreciate the scientific basis in which this
      treatment modality influences wound healing. The biological changes influenced by
      phytochemical compounds can have a positive effect on wound healing, which often
      depends on extract selection and clinical application. A sound understanding of
      the physiological changes that are associated with phytochemical compounds will
      help the clinician to make an appropriate extract selection and guide treatment
      decisions.Tissue adhesion has long been considered a key step in determining a
      bacterium's pathogenicity. The process of preventing infections by decreasing
      bacterial-tissue adhesion has been reported in the literature, with particular
      focus on the antibacterial effects of ingested cranberry juice. Cranberry juice
      has been studied primarily as a "home remedy" in the treatment of urinary tract
      infection with its antiadhesion and/or antibacterial effects in a chronic wound
      needing further investigation.

PMID- 24932956
TI  - Alert! July and October 2014 are key to reporting requirements timeline.

PMID- 24932958
TI  - Use of augmentation agents for treating depression: analysis of a psychiatric
      electronic medical record data set.
AB  - OBJECTIVE: This study evaluated the relationship between patient characteristics
      and augmentation strategies for the treatment of major depressive disorder.
      METHODS: This retrospective, cross-sectional study used data from a psychiatric
      electronic medical record database for patients with depression without psychosis
      or psychotic features who initiated augmentation therapy between January 2001 and
      June 2011. Medical records were evaluated to identify factors predicting use of
      specific augmentation agents, and a multivariate logistic regression model was
      used to assess clinical and demographic predictors of augmentation strategy.
      RESULTS: Of 3,209 patients initiating augmentation therapy for depression, 75%
      received augmentation with an antidepressant combination and 11% received
      augmentation with second-generation antipsychotics. Baseline clinical severity
      (Clinical Global Impressions-Severity score) most strongly and consistently
      predicted augmentation with second-generation antipsychotics. CONCLUSIONS:
      Treatment of patients in specialty settings with depression was often augmented
      with an antidepressant combination, whereas those with severe depression had an
      increased likelihood of augmentation with second-generation antipsychotics.

PMID- 24932957
TI  - Identification of minimum carbohydrate moiety in N-glycosylation sites of brain
      endothelial cell glycoprotein 96 for interaction with Escherichia coli K1 outer
      membrane protein A.
AB  - Bacterial meningitis is a serious central nervous system infection and
      Escherichia coli K1 (E. coli K1) is one of the leading etiological agents that
      cause meningitis in neonates. Outer membrane protein A (OmpA) of E. coli K1 is a
      major virulence factor in the pathogenesis of meningitis, and interacts with
      human brain microvascular endothelial cells (HBMEC) to cross the blood-brain
      barrier. Using site-directed mutagenesis, we demonstrate that two N-glycosylation
      sites (NG1 and NG2) in the extracellular domain of OmpA receptor, Ecgp96 are
      critical for bacterial binding to HBMEC. E. coli K1 invasion assays using CHO
      Lec1 cells that express truncated N-glycans, and sequential digestion of HBMEC
      surface N-glycans using specific glycosidases showed that GlcNAc1-4GlcNAc
      epitopes are sufficient for OmpA interaction with HBMEC. Lack of NG1 and NG2
      sites in Ecgp96 inhibits E. coli K1 OmpA induced F-actin polymerization,
      phosphorylation of protein kinase C-alpha, and disruption of transendothelial
      electrical resistance required for efficient invasion of E. coli K1 in HBMEC.
      Furthermore, the microvessels of cortex and hippocampus of the brain sections of
      E. coli K1 infected mice showed increased expression of glycosylated Ecgp96.
      Therefore, the interface of OmpA and GlcNAc1-4GlcNAc epitope interaction would be
      a target for preventative strategies against E. coli K1 meningitis. 

PMID- 24932959
TI  - A review of the evidence to inform pneumococcal vaccine recommendations for risk
      groups aged 2 years and older.
AB  - For decades, vaccination with the 23-valent polysaccharide pneumococcal vaccine
      (PPV23) has been available for risk groups aged ?2 years to prevent invasive
      pneumococcal disease (IPD). Recently, a 13-valent pneumococcal conjugated vaccine
      (PCV13) has been licensed for use in all age groups. PCV13 may induce better
      protection than PPV23 because of different immunogenic properties. This called
      for a revision of vaccine recommendations for risk groups. We therefore reviewed
      literature on risk groups for IPD, and effectiveness and safety of pneumococcal
      vaccines and supplemented that with information from public health institutes,
      expert consultations and data on IPD epidemiology. We included 187 articles. We
      discuss the implications of the heterogenic vulnerability for IPD within and
      between risk groups, large indirect effects of childhood immunization, and
      limited knowledge on additional clinical benefits of PCV13 in combination with
      PPV23 for the Norwegian recommendations. These are now step-wise and consider the
      need for vaccination, choice of pneumococcal vaccines, and re-vaccination
      interval by risk group.

PMID- 24932960
TI  - Molecular resolution friction microscopy of Cu phthalocyanine thin films on
      dolomite (104) in water.
AB  - The reliability of ultrathin organic layers as active components for molecular
      electronic devices depends ultimately on an accurate characterization of the
      layer morphology and ability to withstand mechanical stresses on the nanoscale.
      To this end, since the molecular layers need to be electrically decoupled using
      thick insulating substrates, the use of AFM becomes mandatory. Here, we show how
      friction force microscopy (FFM) in water allows us to identify the orientation of
      copper(ii)phthalocyanine (CuPc) molecules previously self-assembled on a dolomite
      (104) mineral surface in ultra-high vacuum. The molecular features observed in
      the friction images show that the CuPc molecules are stacked in parallel rows
      with no preferential orientation with respect to the dolomite lattice, while the
      stacking features resemble well the single CuPc crystal structure. This proves
      that the substrate induction is low and makes friction force microscopy in water
      a suitable alternative to more demanding dynamic AFM techniques in ultra-high
      vacuum. 

PMID- 24932961
TI  - "Rigid body rotation" of the left ventricle in hypoplastic right-heart syndrome:
      a case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path
      Study.
AB  - Left ventricular twist results from the movement of two orthogonally oriented
      muscular bands of the helical myocardial structure, with a consequent clockwise
      rotation of the left ventricular base and counterclockwise rotation of the left
      ventricular apex. To the best of the authors' knowledge, this is the first time
      that left ventricular "rigid body rotation", the near absence of left ventricular
      twist in hypoplastic right-heart syndrome, has been demonstrated. 

PMID- 24932962
TI  - Marble burying as a test of the delayed anxiogenic effects of acute
      immobilisation stress in mice.
AB  - A majority of rodent studies characterizing the anxiogenic effects of stress have
      utilized exploration-based models, such as the elevated plus-maze. An alternative
      strategy has relied on ethologically natural behavior such as defensive burying.
      One such paradigm, marble burying, has proven to be an effective behavioral assay
      of the anxiolytic effects of pharmacological manipulations, and of genetically
      modified mouse models. Relatively little, however, is known about the sensitivity
      of this test in assessing the anxiogenic effects of stress. Most of the earlier
      reports have examined the immediate, but not more long-term, effects of
      pharmacological or environmental manipulations in mice. Hence, we used the marble
      burying test to examine if acute immobilization stress leads to enhanced anxiety
      like behavior in C57Bl/6 mice if the test is employed with a significant time
      delay. We find this test to be sensitive enough to detect the anxiogenic effects
      even 10 days after a single episode of 2-h immobilization stress. Our results
      suggest that the marble burying test could serve as a useful behavioral paradigm
      for not only estimating the gradual progression of the anxiogenic impact of
      stress over time, but also raises the possibility of using the temporal delay
      after stress to test the potential efficacy of post-stress interventions with
      anxiolytic drugs. 

PMID- 24932963
TI  - Multivariate temporal pattern analysis applied to the study of rat behavior in
      the elevated plus maze: methodological and conceptual highlights.
AB  - Aim of this article is to illustrate the application of a multivariate approach
      known as t-pattern analysis in the study of rat behavior in elevated plus maze.
      By means of this multivariate approach, significant relationships among
      behavioral events in the course of time can be described. Both quantitative and t
      pattern analyses were utilized to analyze data obtained from fifteen male Wistar
      rats following a trial 1-trial 2 protocol. In trial 2, in comparison with the
      initial exposure, mean occurrences of behavioral elements performed in protected
      zones of the maze showed a significant increase counterbalanced by a significant
      decrease of mean occurrences of behavioral elements in unprotected zones.
      Multivariate t-pattern analysis, in trial 1, revealed the presence of 134 t
      patterns of different composition. In trial 2, the temporal structure of behavior
      become more simple, being present only 32 different t-patterns. Behavioral
      strings and stripes (i.e. graphical representation of each t-pattern onset) of
      all t-patterns were presented both for trial 1 and trial 2 as well. Finally,
      percent distributions in the three zones of the maze show a clear-cut increase of
      t-patterns in closed arm and a significant reduction in the remaining zones.
      Results show that previous experience deeply modifies the temporal structure of
      rat behavior in the elevated plus maze. In addition, this article, by
      highlighting several conceptual, methodological and illustrative aspects on the
      utilization of t-pattern analysis, could represent a useful background to employ
      such a refined approach in the study of rat behavior in elevated plus maze. 

PMID- 24932964
TI  - The effect of swallowing treatments on corticobulbar excitability: a review of
      transcranial magnetic stimulation induced motor evoked potentials.
AB  - Transcranial magnetic stimulation (TMS) has been used extensively as a method of
      investigating the corticomotor physiology of many motor tasks, including healthy
      and disordered swallowing. Changes in excitability of cortical projections to
      various swallowing muscles have been documented in response to treatments with
      TMS induced motor evoked potentials (MEPs). These studies have provided valuable
      insight into CNS response to swallowing impairment, and more importantly, the
      adaptations associated with functional recovery. However, unique obstacles are
      presented when investigating corticobulbar neurophysiology associated with the
      complex task of swallowing. Stringent methodological control and supplementary
      outcome measures are required to ensure robust and clinically applicable
      findings. This article offers a tutorial for the researcher who may be
      considering the use of TMS for investigating changes in cortical excitability
      associated with various swallowing paradigms. Included is a review of the
      mechanisms of TMS and what can be measured with this technique, a summary of
      existing research using MEPs to investigate swallowing, a review of
      methodological factors that may influence outcomes, and proposed directions for
      new areas of research. 

PMID- 24932965
TI  - A simple and reliable method to perform biomechanical evaluation of postoperative
      nerve adhesions.
AB  - BACKGROUND: Perineural fibrotic adhesions are among the major complications of
      peripheral nerve surgery. While different experimental models have been used for
      the pre-clinical testing of anti-adherential strategies, the methods used so far
      to induce scar tissue appear to be poorly standardized and reproducible. NEW
      METHOD: Thirty adult mice were used. Two methods were tested: the first one is
      based on burning the perineural muscular bed with a diathermocoagulator, while
      the second is based on direct scratching of the nerve surface with a cotton swab.
      After 3 weeks, the fibrotic reaction was assessed by measuring the peak pull out
      force of the nerve from muscular bed by means of a new tool specifically devised
      for biomechanical assessment of scar tissue formation. Moreover, histological
      analysis with specific collagen stain was also carried out. RESULTS: Both methods
      produced fibrotic reaction. Statistical analysis of biomechanical data showed a
      significant difference between burning and scratching group compared to the
      control sham operated group. No significant differences were detected between
      burning and scratching group. Histological analysis showed the presence of
      perineural scar tissue in both groups, though with a different distribution
      pattern. COMPARISON WITH OTHER METHODS: This protocol is easier to perform. The
      tool used for biomechanical evaluation is reliable and cheap. CONCLUSIONS: Both
      methods for perineural scar formation are effective and simple. They represent
      reproducible models for the study of the anti-adherential strategies. Yet,
      biomechanical testing with the device that we have developed proved to be a
      reliable and simple method for the quantitative assessment of the degree of
      perineural adhesion formation.

PMID- 24932966
TI  - Engineered RNase P ribozymes effectively inhibit human cytomegalovirus gene
      expression and replication.
AB  - RNase P ribozyme can be engineered to be a sequence-specific gene-targeting agent
      with promising application in both basic research and clinical settings. By using
      an in vitro selection system, we have previously generated RNase P ribozyme
      variants that have better catalytic activity in cleaving an mRNA sequence than
      the wild type ribozyme. In this study, one of the variants was used to target the
      mRNA encoding human cytomegalovirus (HCMV) essential transcription factor
      immediate-early protein 2 (IE2). The variant was able to cleave IE2 mRNA in vitro
      50-fold better than the wild type ribozyme. A reduction of about 98% in IE2
      expression and a reduction of 3500-fold in viral production was observed in HCMV
      infected cells expressing the variant compared to a 75% reduction in IE2
      expression and a 100-fold reduction in viral production in cells expressing the
      ribozyme derived from the wild type sequence. These results suggest that ribozyme
      variants that are selected to be highly active in vitro are also more effective
      in inhibiting the expression of their targets in cultured cells. Our study
      demonstrates that RNase P ribozyme variants are efficient in reducing HCMV gene
      expression and growth and are potentially useful for anti-viral therapeutic
      application. 

PMID- 24932967
TI  - Yeast cell lysis enhances dimethyl trisulfide formation in sake.
AB  - The present study showed that the lysis of yeast cells and subsequent release of
      cell contents in sake mash accelerated dimethyl trisulfide (DMTS) formation.
      Among these, heat unstable and relatively high molecular weight compounds were
      assumed to be enzymes; thus, enzymatic reactions probably contribute to DMTS
      formation. 

PMID- 24932968
TI  - Functional analysis of bifidobacterial promoters in Bifidobacterium longum and
      Escherichia coli using the alpha-galactosidase gene as a reporter.
AB  - Heterologous gene expression in bifidobacteria requires weak, strong, and
      inducible promoters depending on the objectives of different expression studies.
      Weak promoters in Escherichia coli can also be desirable for stable heterologous
      gene cloning. Here, we developed a reporter system using the Bifidobacterium
      longum alpha-galactosidase gene and investigated the activity and inducibility of
      seven bifidobacterial promoters in B. longum and their activities in E. coli.
      These studies revealed diverse promoter activities. Three promoters were highly
      active in B. longum, but only slightly active in E. coli. Among these, two
      phosphoketolase gene (xfp) promoters exhibited strong activity in B. longum cells
      grown on glucose. In contrast, the promoter activity of the fructose transporter
      operon (fruEKFG) was strongly induced by carbohydrates other than glucose,
      including fructose, xylose, and ribose. These promoters will allow strong or
      highly inducible expression in bifidobacteria and stable gene cloning in E. coli.
      In contrast to the functions of these promoters, the promoter of sucrose
      utilization operon cscBA showed very high activity in E. coli but low activity in
      B. longum. Other three promoters were functional in both B. longum and E. coli.
      In particular, two sucrose phosphorylase gene (scrP) promoters showed inducible
      activity by sucrose and raffinose in B. longum, indicating their applicability
      for regulated expression studies. The diverse promoter functions revealed in this
      study will contribute to enabling the regulated expression of heterologous genes
      in bifidobacteria research. 

PMID- 24932969
TI  - Polyhydroxyalkanoate production by a novel bacterium Massilia sp. UMI-21 isolated
      from seaweed, and molecular cloning of its polyhydroxyalkanoate synthase gene.
AB  - We successfully isolated one microorganism (UMI-21) from Ulva, a green algae that
      contains starch. The strain UMI-21 can produce polyhydroxyalkanoate (PHA) from
      starch, maltotriose, or maltose as a sole carbon source. Taxonomic studies and
      16S rDNA sequence analysis revealed that strain UMI-21 was phylogenetically
      related to species of the genus Massilia. The PHA content under the cultivation
      condition using a 10-L jar fermentor was 45.5% (w/w). This value was higher than
      that obtained after cultivation in a flask, suggesting the possibility of large
      scale PHA production by UMI-21 from starch. A major issue for the industrial
      production of microbial PHAs is the very high production cost. Starch is a
      relatively inexpensive substrate that is also found in abundant seaweeds such as
      Ulva. Therefore, the strain isolated in this study may be very useful for
      producing PHA from seaweeds containing polysaccharides such as starch. In
      addition, a 3.7-kbp DNA fragment containing the whole PHA synthase gene (phaC)
      was obtained from the strain UMI-21. The results of open reading frame (ORF)
      analysis suggested that the DNA fragment contained two ORFs, which were composed
      of 1740 (phaC) and 564 bp (phaR). The deduced amino acid sequence of PhaC from
      strain UMI-21 shared high similarity with PhaC from Ralstonia eutropha, which is
      a representative PHA-producing bacterium with a class I PHA synthase. This is the
      first report for the cloning of the PHA synthase gene from Massilia species. 

PMID- 24932971
TI  - Formation of supported lipid bilayers by vesicle fusion: effect of deposition
      temperature.
AB  - We have investigated the effect of deposition temperature on supported lipid
      bilayer formation via vesicle fusion. By using several complementary surface
      sensitive techniques, we demonstrate that despite contradicting literature on the
      subject, high-quality bilayers can be formed below the main phase-transition
      temperature of the lipid. We have carefully studied the formation mechanism of
      supported DPPC bilayers below and above the lipid melting temperature (Tm) by
      quartz crystal microbalance and atomic force microscopy under continuous flow
      conditions. We also measured the structure of lipid bilayers formed below or
      above Tm by neutron reflection and investigated the effect of subsequent cooling
      to below the Tm. Our results clearly show that a continuous supported bilayer can
      be formed with high surface coverage below the lipid Tm. We also demonstrate that
      the high dissipation responses observed during the deposition process by QCM-D
      correspond to vesicles absorbed on top of a continuous bilayer and not to a
      surface-supported vesicular layer as previously reported. 

PMID- 24932970
TI  - Contributions of Fusarium virguliforme and Heterodera glycines to the disease
      complex of sudden death syndrome of soybean.
AB  - BACKGROUND: Sudden death syndrome (SDS) of soybean caused by Fusarium
      virguliforme spreads and reduces soybean yields through the North Central region
      of the U.S. The fungal pathogen and Heterodera glycines are difficult to manage.
      METHODOLOGY/PRINCIPAL FINDINGS: The objective was to determine the contributions
      of H. glycines and F. virguliforme to SDS severity and effects on soybean yield.
      To quantify DNA of F. virguliforme in soybean roots and soil, a specific real
      time qPCR assay was developed. The assay was used on materials from soybean field
      microplots that contained in a four-factor factorial-design: (i) untreated or
      methyl bromide-fumigated; (ii) non-infested or infested with F. virguliforme;
      (iii) non-infested or infested with H. glycines; (iv) natural precipitation or
      additional weekly watering. In years 2 and 3 of the trial, soil and watering
      treatments were maintained. Roots of soybean 'Williams 82' were collected for
      necrosis ratings at the full seed growth stage R6. Foliar symptoms of SDS (area
      under the disease progress curve, AUDPC), root necrosis, and seed yield
      parameters were related to population densities of H. glycines and the relative
      DNA concentrations of F. virguliforme in the roots and soil. The specific and
      sensitive real time qPCR was used. Data from microplots were introduced into
      models of AUDPC, root necrosis, and seed yield parameters with the frequency of
      H. glycines and F. virguliforme, and among each other. The models confirmed the
      close interrelationship of H. glycines with the development of SDS, and allowed
      for predictions of disease risk based on populations of these two pathogens in
      soil. CONCLUSIONS/SIGNIFICANCE: The results modeled the synergistic interaction
      between H. glycines and F. virguliforme quantitatively in previously infested
      field plots and explained previous findings of their interaction. Under these
      conditions, F. virguliforme was mildly aggressive and depended on infection of H.
      glycines to cause highly severe SDS.

PMID- 24932972
TI  - Long-term intake of soyabean phytosterols lowers serum TAG and NEFA
      concentrations, increases bile acid synthesis and protects against fatty liver
      development in dyslipidaemic hamsters.
AB  - Various human trials and pre-clinical studies have suggested that dietary plant
      sterols possess hypotriacylglycerolaemic properties apart from their cholesterol
      lowering properties. We hypothesised that phytosterols (PS) might attenuate
      triacylglycerolaemia by interfering with the deleterious effects of cholesterol
      overload in the liver. In the present study, twenty hamsters (Mesocricetus
      auratus) with diet-induced combined hyperlipidaemia were fed a high-fat diet
      (HFD, n 10) or a HFD supplemented with soyabean PS (n 10) for 40 d. In parallel,
      a healthy group was fed a standard diet (n 10). PS normalised fasting plasma
      cholesterol concentrations completely after 20 d and were also able to normalise
      serum TAG and NEFA concentrations after 40 d. HFD feeding caused microvesicular
      steatosis and impaired the expression of key genes related to fatty acid
      oxidation such as PPARA, carnitine palmitoyltransferase-Ialpha (CPT1A) and
      phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver. PS treatment completely
      protected against HFD-induced steatosis and resulted in a normalised hepatic gene
      expression profile. The protection of the hepatic function by PS was paralleled
      by increased faecal cholesterol excretion along with a 2-fold increase in the
      biliary bile acid (BA):cholesterol ratio. The present study supports the
      conclusion that long-term consumption of PS can reduce serum TAG and NEFA
      concentrations and can protect against the development of fatty liver via
      different mechanisms, including the enhancement of BA synthesis. The results of
      the present study place these compounds as promising hepatoprotective agents
      against fatty liver and its derived pathologies.

PMID- 24932973
TI  - Isolation and characterization of microsatellite markers and analysis of genetic
      diversity in Chinese jujube (Ziziphus jujuba Mill.).
AB  - Chinese jujube (Ziziphus jujuba Mill, 2n = 2* = 24, Rhamnaceae) is an
      economically important Chinese native species. It has high nutritional value, and
      its medicinal properties have led to extensive use in traditional oriental
      medicine. The characterization of genotypes using molecular markers is important
      for genetic studies and plant breeding. However, few simple sequence repeat (SSR)
      markers are available for this species. In this study, 1,488 unique SSR clones
      were isolated from Z. jujuba 'Dongzao' using enriched genomic libraries coupled
      with a three-primer colony PCR screening strategy, yielding a high enrichment
      rate of 73.3%. Finally, 1,188 (80.87%) primer pairs were amplified successfully
      in the size expected for 'Dongzao'. A total of 350 primer pairs were further
      selected and evaluated for their ability to detect polymorphisms across a panel
      of six diverse cultivars; among these, 301 primer pairs detected polymorphisms,
      and the polymorphism information content (PIC) value across all loci ranged from
      0.15 to 0.82, with an average of 0.52. An analysis of 76 major cultivars employed
      in Chinese jujube production using 31 primer pairs revealed comparatively high
      genetic diversity among these cultivars. Within-population differences among
      individuals accounted for 98.2% of the observed genetic variation. Neighbor
      joining clustering divided the cultivars into three main groups, none of which
      correspond to major geographic regions, suggesting that the genetics and
      geographical origin of modern Chinese jujube cultivars might not be linked. The
      current work firstly reports the large-scale development of Chinese jujube SSR
      markers. The development of these markers and their polymorphic information
      represent a significant improvement in the available Chinese jujube genomic
      resources and will facilitate both genetic and breeding applications, further
      accelerating the development of new cultivars.

PMID- 24932975
TI  - Phloretin promotes osteoclast apoptosis in murine macrophages and inhibits
      estrogen deficiency-induced osteoporosis in mice.
AB  - Bone-remodeling imbalance induced by increased osteoclast formation and bone
      resorption is known to cause skeletal diseases such as osteoporosis. The
      reduction of estrogen levels at menopause is one of the strongest risk factors
      developing postmenopausal osteoporosis. This study investigated osteoprotective
      effects of the dihydrochalcone phloretin found in apple tree leaves on bone loss
      in ovariectomized (OVX) C57BL/6 female mice as a model for postmenopausal
      osteoporosis. OVX demoted bone mineral density (BMD) of mouse femurs, reduced
      serum 17beta-estradiol level and enhanced serum receptor activator of NF-kappaB
      ligand (RANKL)/osteoprotegerin ratio with uterine atrophy. Oral administration of
      10 mg/kg phloretin to OVX mice for 8 weeks improved such effects, compared to
      sham-operated mice. Phloretin attenuated TRAP activity and cellular expression of
      beta3 integrin and carbonic anhydrase II augmented in femoral bone tissues of OVX
      mice. This study further examined that osteogenic activity of phloretin in RANKL
      differentiated Raw 264.7 macrophages into mature osteoclasts. Phloretin at 1-20
      MUM stimulated Smac expression and capase-3 activation concurrently with nuclear
      fragmentation of multi-nucleated osteoclasts, indicating that this compound
      promoted osteoclast apoptosis. Consistently, phloretin enhanced bcl-2 induction
      but diminished bax expression. Furthermore, phloretin activated ASK-1-diverged
      JNK and p38 MAPK signaling pathways in mature osteoclasts, whereas it dose
      dependently inhibited the RANKL-stimulated activation of ERK. Therefore,
      phloretin manipulated ASK-1-MAPK signal transduction leading to transcription of
      apoptotic genes. Phloretin was effective in preventing estrogen deficiency
      induced osteoclastogenic resorption.

PMID- 24932976
TI  - When can a normal dose be an overdose? Who is at risk?

PMID- 24932974
TI  - A monoterpene, unique component of thyme honeys, induces apoptosis in prostate
      cancer cells via inhibition of NF-kappaB activity and IL-6 secretion.
AB  - We have previously demonstrated that Greek thyme honey inhibits significantly the
      cell viability of human prostate cancer cells. Herein, 15 thyme honey samples
      from several regions of Greece were submitted to phytochemical analysis for the
      isolation, identification and determination (through modern spectral means) of
      the unique thyme honey monoterpene, the compound trihydroxy ketone E-4-(1,2,4
      trihydroxy-2,6,6-trimethylcyclohexyl)-but-3-en-2-one. We investigated the anti
      growth and apoptotic effects of the trihydroxy ketone on PC-3 human androgen
      independent prostate cancer cells using MTT assay and Annexin V-FITC
      respectively. The molecular pathways involved to such effects were further
      examined by evaluating its ability to inhibit (a) the NF-kappaB phosphorylation
      (S536), (b) JNK and Akt phosphorylation (Thr183/Tyr185 and S473 respectively) and
      (c) IL-6 production, using ELISA method. The anti-microbial effects of the
      trihydroxy ketone against a panel of nine pathogenic bacteria and three fungi
      were also assessed. The trihydroxy ketone exerted significant apoptotic activity
      in PC-3 prostate cancer cells at 100 MUM, while it inhibited NF-kappaB
      phosphorylation and IL-6 secretion at a concentration range 10(-6)-10(-4)M. Akt
      and JNK signaling were not found to participate in this process. The trihydroxy
      ketone exerted significant anti-microbial profile against many human pathogenic
      bacteria and fungi (MIC values ranged from 0.04 to 0.57 mg/ml). Conclusively, the
      Greek thyme honey-derived monoterpene exerted significant apoptotic activity in
      PC-3 cells, mediated, at least in part, through reduction of NF-kappaB activity
      and IL-6 secretion and may play a key role in the anti-growth effect of thyme
      honey on prostate cancer cells.

PMID- 24932977
TI  - Appropriate head position for nasotracheal intubation by using lightwand device
      (Trachlight).
AB  - The purpose of this study was to determine the relationship between the head
      position and the subsequent ease of nasotracheal intubation by using the
      lightwand device Trachlight (TL). Patients requiring nasotracheal intubation were
      subdivided into 3 groups according to the intubated head position (group S:
      sniffing position; group E: extension position; and group N: neutral position).
      The number of attempts, the total intubation time, and the failures of the TL
      intubation were recorded. Intubation difficulty by means of TL was assessed by
      the ordinal 6-point scale. Of the 300 patients enrolled in the study, TL
      intubation was successful in 91.3% of them. There was no significant difference
      in the success rate of the first attempt between the groups. No correlation
      between the ordinal scale and the head position was observed. The total
      intubation time and the ratio of "unsuccessful" cases were not significantly
      different among the 3 groups. TL is an effective alternative for patients who
      require nasotracheal intubation. Our study did not determine the most favorable
      head position for nasotracheal intubation with the TL, so we recommend that
      nasotracheal intubation with TL be started with the head in the neutral position
      and then changed to a more appropriate position, if necessary, on an individual
      basis.

PMID- 24932978
TI  - Lidocaine concentration in mandibular bone after subperiosteal infiltration
      anesthesia decreases with elevation of periosteal flap and irrigation with
      saline.
AB  - It has been reported that the action of infiltration anesthesia on the jawbone is
      attenuated significantly by elevation of the periosteal flap with saline
      irrigation in clinical studies; however, the reason is unclear. Therefore, the
      lidocaine concentration in mandibular bone after subperiosteal infiltration
      anesthesia was measured under several surgical conditions. The subjects were 48
      rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000
      epinephrine (adrenaline) was injected into the right mandibular angle and left
      mandibular body, respectively. Under several surgical conditions (presence or
      absence of periosteal flap, and presence or absence of saline irrigation), both
      mandibular bone samples were removed at a fixed time after subperiosteal
      infiltration anesthesia. The lidocaine concentration in each mandibular bone
      sample was measured by high-performance liquid chromatography. As a result,
      elevation of the periosteal flap with saline irrigation significantly decreased
      the lidocaine concentration in the mandibular bone. It is suggested that the
      anesthetic in the bone was washed out by saline irrigation. Therefore,
      supplemental conduction and/or general anesthesia should be utilized for long
      operations that include elevation of the periosteal flap with saline irrigation.

PMID- 24932980
TI  - Do patients fear undergoing general anesthesia for oral surgery?
AB  - Many patients undergoing major surgery have more fear of the general anesthesia
      than the procedure. This appears to be reversed with oral surgery. Therefore,
      patients need to be as well informed about this aspect as the surgical operation.

PMID- 24932979
TI  - Anesthetic efficacy of a combination of 0.5 M mannitol plus 36.8 mg of lidocaine
      with 18.4 MUg epinephrine in maxillary infiltration: a prospective, randomized,
      single-blind study.
AB  - The purpose of this prospective, randomized, single-blind study was to determine
      the anesthetic efficacy of lidocaine with epinephrine compared to lidocaine with
      epinephrine plus 0.5 M mannitol in maxillary lateral incisor infiltrations. Forty
      one subjects randomly received 2 maxillary lateral infiltrations consisting of a
      1.84-mL solution of 36.8 mg lidocaine with 18.4 MUg epinephrine (control
      solution) and a 2.90-mL solution of 36.8 mg lidocaine with 18.4 MUg epinephrine
      (1.84 mL) plus 0.5 M mannitol (1.06 mL) in 2 separate appointments spaced at
      least 1 week apart. The maxillary lateral incisor was blindly electric pulp
      tested in 2-minute cycles for 60 minutes postinjection. No response from the
      subject to the maximum output (a reading of 80) of the pulp tester was used as
      the criterion for pulpal anesthesia. Total percent pulpal anesthesia was defined
      as the total of all pulpal anesthesia readings (at output of 80) over the 60
      minute test period. Pain during solution deposition and postoperative pain were
      also measured. The results demonstrated that a 2.90-mL solution of 36.8 mg
      lidocaine with 18.4 MUg epinephrine (1.84 mL) plus 0.5 M mannitol (1.06 mL) was
      not statistically significantly superior to a 1.84-mL solution of 36.8 mg
      lidocaine with 18.4 MUg epinephrine. The pain of solution deposition was lower
      with the lidocaine/mannitol formulation. Postoperative pain was not statistically
      significantly different between the lidocaine/mannitol formulation and the
      lidocaine formulation without mannitol. We concluded that adding 0.5 M mannitol
      to a lidocaine with epinephrine formulation was not significantly more effective
      in achieving a greater percentage of total pulpal anesthesia (as defined in this
      study) than a lidocaine formulation without mannitol in the maxillary lateral
      incisor.

PMID- 24932981
TI  - Cerebrovascular accident under anesthesia during dental surgery.
AB  - Stroke, or cerebrovascular accident (CVA), is a medical emergency that may lead
      to permanent neurological damage, complications, and death. The rapid loss of
      brain function due to disruption of the blood supply to the brain is caused by
      blockage (thrombosis, arterial embolism) or hemorrhage. The incidence of CVA
      during anesthesia for noncardiac nonvascular surgery is as high as 1% depending
      on risk factors. Comprehensive preoperative assessment and good perioperative
      management may prevent a CVA. However, should an ischemic event occur,
      appropriate and rapid management is necessary to minimize the deleterious effects
      caused to the patient. This case report describes a patient who had an ischemic
      CVA while under general anesthesia for dental alveolar surgery and discusses the
      anesthesia management.

PMID- 24932982
TI  - Essentials of airway management, oxygenation, and ventilation: part 1: basic
      equipment and devices.
AB  - Offices and outpatient dental facilities must be properly equipped with devices
      for airway management, oxygenation, and ventilation. Optimizing patient safety
      using crisis resource management (CRM) involves the entire dental office team
      being familiar with airway rescue equipment. Basic equipment for oxygenation,
      ventilation, and airway management is mandated in the majority of US dental
      offices per state regulations. The immediate availability of this equipment is
      especially important during the administration of sedation and anesthesia as well
      as the treatment of medical urgencies/emergencies. This article reviews basic
      equipment and devices essential in any dental practice whether providing local
      anesthesia alone or in combination with procedural sedation. Part 2 of this
      series will address advanced airway devices, including supraglottic airways and
      armamentarium for tracheal intubation and invasive airway procedures.

PMID- 24932985
TI  - Lubricin expression in human osteoarthritic knee meniscus and synovial fluid: a
      morphological, immunohistochemical and biochemical study.
AB  - The purpose of this study was to investigate the expression of lubricin, the
      product of the human PRG4 (proteoglycan 4) gene, in menisci and synovial fluid
      from normal donors and patients with osteoarthritis (OA), using a combination of
      histology, immunohistochemistry, ELISA and Western blotting analysis, to provide
      further insight on the role of this protein in the progression of OA and
      pathological processes in the meniscus. Lubricin expression was studied in
      samples from 40 patients and in 9 normal donors after arthroscopic partial
      meniscectomy. Histological analysis confirmed normal microanatomy and the absence
      of structural changes in control samples. Menisci derived from OA patients showed
      evidence of structural alterations, fibrillations and clefts. Immunohistochemical
      analysis revealed very strong lubricin immunostaining in normal menisci in
      contrast to weak/moderate staining seen in osteoarthritic menisci. Quantitative
      ELISA and Western blot analysis confirmed the above results. The findings of this
      study support the notion that changes in lubricin expression and boundary
      lubricating ability of cartilage is followed by the development of OA. This study
      could provide the biological foundation for the development of novel therapeutic
      treatments, to be applied before the surgery, for the prevention of post
      traumatic cartilage damage. 

PMID- 24932986
TI  - Magnetic resonance-guided high-intensity focused ultrasound treatment of locally
      advanced pancreatic adenocarcinoma: preliminary experience for pain palliation
      and local tumor control.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility of magnetic
      resonance-guided focused ultrasound (MRgFUS) ablation for pain palliation and
      local tumor control in selected patients with unresectable primary pancreatic
      adenocarcinoma. MATERIALS AND METHODS: After providing dedicated informed
      consent, 7 patients with histologically proven unresectable pancreatic
      adenocarcinoma underwent MRgFUS treatment on a dedicated 3-T unit featuring a
      dedicated ablation system. All lesions were evaluated for device accessibility
      before the treatment. Procedures of MRgFUS were performed with the patients under
      general anesthesia with constant controlled respiration. Clinical assessment
      included evaluation of symptom severity using a visual analog scale before and
      after the treatment. Imaging follow-up, including both computed tomographic and
      magnetic resonance examinations, was performed immediately after the treatment
      and at 3 and 6 months to evaluate the effects of MRgFUS on the targeted tumor and
      the occurrence, if any, of procedure-related complications. RESULTS: The MRgFUS
      ablation was successfully performed in 6 patients; no adverse events were
      observed during or after the procedure. In a single patient, lesion accessibility
      was limited at treatment time, and the procedure was suspended. The visual analog
      scale score decreased in all patients from a mean (SD) of 7 (1) to 3 (1) after
      the treatment. Follow-up imaging results revealed negligible (n = 1) or no (n =
      5) tumor regrowth within the ablation area. One patient died because of a
      metastatic disease 13 months after the treatment, whereas the other 5 are
      nonprogressing survivors at 6 and 8 months after the treatment. CONCLUSIONS: Our
      preliminary clinical experience suggests that MRgFUS is a feasible and repeatable
      ablative technique in selected patients with unresectable and device-accessible
      pancreatic adenocarcinoma.

PMID- 24932987
TI  - Modified simple limbal epithelial transplantation using cryopreserved amniotic
      membrane for unilateral limbal stem cell deficiency.
AB  - PURPOSE: To report the results of simple limbal epithelial transplantation using
      a double-layered cryopreserved amniotic membrane graft for the management of
      unilateral limbal stem cell deficiency. DESIGN: Retrospective case series.
      METHODS: Four consecutive patients with unilateral partial (2 eyes) and total (2
      eyes) limbal stem cell deficiency secondary to ocular surface burns (2 eyes),
      trauma (1 eye) and conjunctival melanoma treatment (1 eye) underwent modified
      simple limbal epithelial transplantation at Bascom Palmer Eye Institute.
      Preoperative and postoperative visual acuity and quality of corneal epithelium
      were evaluated. RESULTS: The patients were followed up for a mean +/- standard
      deviation of 7.5 +/- 1.3 months. The donor eye returned to a healthy state in all
      patients. All patients had significant improvement in visual acuity and
      resolution of ocular pain in the affected eye. Regular corneal epithelium and a
      quiet ocular surface were obtained in all patients by a median of 4 weeks.
      CONCLUSIONS: Compared with the currently used surgical techniques for management
      of limbal stem cell deficiency, simple limbal epithelial transplantation seems to
      be a safe, reproducible, and effective alternative. The use of a double layer
      allows more protection for the explant without impacting outcomes. Also, the use
      of cryopreserved amniotic membrane allows surgeons to perform this procedure in
      the Unites States. More cases with longer follow-up will be needed to assess the
      outcomes further.

PMID- 24932988
TI  - Pathogenesis and treatment of maculopathy associated with cavitary optic disc
      anomalies.
AB  - PURPOSE: To propose a unifying theory regarding the pathogenesis of maculopathy
      associated with cavitary optic disc anomalies and to describe a rational approach
      to achieving a permanent cure in affected eyes. DESIGN: Interpretive essay.
      METHODS: Review and synthesis of selected literature, with interpretation and
      perspective in relating pathoanatomic features to pathogenesis and treatment.
      RESULTS: Congenital cavitary anomalies of the optic disc, including typical
      coloboma, optic pit (and other atypical colobomas), morning glory anomaly, and
      extrapapillary cavitation, are associated with an enigmatic maculopathy
      characterized by schisis-like thickening and serous detachment. The unifying
      anatomic theme of these anomalies is the presence of a scleral (or lamina
      cribrosa) defect permitting anomalous communications between intraocular and
      extraocular spaces. These communications enable the critical pathogenic mechanism
      responsible for the maculopathy, namely, dynamic fluctuations in the gradient
      between intraocular and intracranial pressures that direct the movement of fluid
      (vitreous humor or cerebrospinal fluid) into and under the retina. Vitreous
      traction does not seem to play a significant pathogenic role. Permanent cure of
      the maculopathy requires either elimination of the translaminar pressure gradient
      or closure of the pathway for fluid flow into the retina. We advocate carefully
      titrated juxtapapillary laser photocoagulation followed by vitrectomy with gas
      tamponade for creation of a permanent intraretinal and subretinal fluid barrier.
      CONCLUSIONS: The peculiar features of cavitary optic disc maculopathy can be
      explained only by considering the pressure gradients that develop along anomalous
      communications between intraocular and extraocular spaces. A permanent cure for
      this condition can be achieved by closing the pathway for fluid migration from
      the cavitary lesion into and under the retina.

PMID- 24932989
TI  - A prospective randomized clinical evaluation of 3 presbyopia-correcting
      intraocular lenses after cataract extraction.
AB  - PURPOSE: To compare contrast sensitivity, visual acuity (VA), and halos in
      subjects bilaterally implanted with 1 of 3 FDA-approved presbyopia-correcting
      intraocular lenses. DESIGN: Prospective, randomized, partially masked,
      multicenter clinical trial. METHODS: Seventy-eight subjects were randomized
      sequentially for bilateral implantation with the Crystalens AO (Bausch & Lomb
      Surgical), AcrySof IQ ReSTOR +3.0 (Alcon Laboratories), or Tecnis Multifocal
      (Abbott Medical Optics) lenses. Subjects were evaluated through visit 4 (4 to 6
      months after surgery) with the following monocular and binocular assessments:
      high- and low-contrast VA, contrast sensitivity without glare, halos or
      starbursts, defocus curves, optical scatter, retinal point spread function, and
      safety. RESULTS: The Crystalens AO and ReSTOR +3.0 demonstrated better monocular
      and binocular contrast sensitivity without glare at low to mid spatial
      frequencies compared with the Tecnis Multifocal lens. Binocular uncorrected
      distance VA was not significantly different between the 3 lenses. The Crystalens
      AO had significantly better binocular low-contrast distance-corrected VA than the
      ReSTOR +3.0 and better mean monocular low-contrast DCVA than the Tecnis
      Multifocal lens. The Crystalens AO demonstrated significantly better monocular
      and binocular uncorrected and distance-corrected intermediate VA than the ReSTOR
      +3.0 or Tecnis Multifocal lenses. The ReSTOR+3.0 lens had significantly better
      monocular and binocular uncorrected and distance-corrected near VA tested at 40
      cm compared with the Crystalens AO and Tecnis Multifocal lens. The Crystalens AO
      elicited significantly less halos than the Tecnis Multifocal lens and less
      optical scatter than the ReSTOR +3.0 or Tecnis Multifocal lens. CONCLUSIONS: The
      Crystalens AO had statistically better uncorrected intermediate VA and distance
      corrected intermediate VA than the ReSTOR +3.0 or Tecnis Multifocal lenses and
      fewer photic phenomenon than the Tecnis Multifocal lens. Both multifocals had
      better distance-corrected near VA and uncorrected near VA than the Crystalens AO.
      These findings may guide intraocular lens selection for individual patients
      seeking to optimize vision at specific vergences or lighting conditions.

PMID- 24932990
TI  - Norsampsones A-D, four new decarbonyl polycyclic polyprenylated
      acylphloroglucinols from Hypericum sampsonii.
AB  - Norsampsones A-D (1-4), four new decarbonyl polycyclic polyprenylated
      acylphloroglucinols, together with a new biogenetically related compound
      hypersampsone M (5), were isolated from the aerial parts of Hypericum sampsonii.
      Norsampsones A-D featured an unprecedented carbon skeleton with the loss of C-2
      carbonyl in the phloroglucinol ring. All structures were determined by extensive
      NMR spectroscopic methods, ECD calculation, and single-crystal X-ray diffraction.

PMID- 24932991
TI  - Exercise enhances wound healing and prevents cancer progression during aging by
      targeting macrophage polarity.
AB  - Physical activity, which can include regular and repetitive exercise training,
      has been shown to decrease the incidence of age-related diseases. Aging is
      characterized by aberrant immune responses, including impaired wound healing and
      increased cancer risk. The behavior and polarized phenotype of tissue macrophages
      are distinct between young and old organisms. The balance of M1 and M2
      macrophages is altered in the aged tissue microenvironment, with a tilt towards
      an M2-dominant macrophage population, as well as its associated signaling
      pathways. These M2-type responses may result in unresolved inflammation and
      create an environment that impairs wound healing and is favorable for cancer
      growth. We discuss the concept that exercise training can improve the regulation
      of macrophage polarization and normalize the inflammatory process, and thereby
      exert anticancer effects and enhance wound healing in older humans. 

PMID- 24932992
TI  - Renzo Guerrini: seeing things other people don't see.

PMID- 24932995
TI  - Effectively responding to tactile stimulation: do homologous cue and effector
      locations really matter?
AB  - We report a study designed to investigate the extent to which speeded behavioral
      responses following tactile stimulation are influenced by differences in neural
      conduction latencies at different body sites and/or by the characteristics of the
      compatibility between the cue and effector. The results showed that it may not be
      particularly desirable to present tactile cues (e.g., warning signals) to an
      interface operator's feet if a speeded foot response is required, for even though
      such an arrangement maximizes the set-level compatibility between the stimulus
      and the response, it turns out that response latencies are primarily determined
      by conduction latencies through the peripheral nervous system. 

PMID- 24932996
TI  - Audiovisual beat induction in complex auditory rhythms: point-light figure
      movement as an effective visual beat.
AB  - This study investigated whether explicit beat induction in the auditory, visual,
      and audiovisual (bimodal) modalities aided the perception of weakly metrical
      auditory rhythms, and whether it reinforced attentional entrainment to the beat
      of these rhythms. The visual beat-inducer was a periodically bouncing point-light
      figure, which aimed to examine whether an observed rhythmic human movement could
      induce a beat that would influence auditory rhythm perception. In two tasks,
      participants listened to three repetitions of an auditory rhythm that were
      preceded and accompanied by (1) an auditory beat, (2) a bouncing point-light
      figure, (3) a combination of (1) and (2) synchronously, or (4) a combination of
      (1) and (2), with the figure moving in anti-phase to the auditory beat.
      Participants reproduced the auditory rhythm subsequently (Experiment 1), or
      detected a possible temporal change in the third repetition (Experiment 2). While
      an explicit beat did not improve rhythm reproduction, possibly due to the
      syncopated rhythms when a beat was imposed, bimodal beat induction yielded
      greater sensitivity to a temporal deviant in on-beat than in off-beat positions.
      Moreover, the beat phase of the figure movement determined where on-beat accents
      were perceived during bimodal induction. Results are discussed with regard to
      constrained beat induction in complex auditory rhythms, visual modulation of
      auditory beat perception, and possible mechanisms underlying the preferred visual
      beat consisting of rhythmic human motions. 

PMID- 24932994
TI  - The effects of school holidays on transmission of varicella zoster virus, England
      and Wales, 1967-2008.
AB  - BACKGROUND: Changes in children's contact patterns between termtime and school
      holidays affect the transmission of several respiratory-spread infections.
      Transmission of varicella zoster virus (VZV), the causative agent of chickenpox,
      has also been linked to the school calendar in several settings, but temporal
      changes in the proportion of young children attending childcare centres may have
      influenced this relationship. METHODS: We used two modelling methods (a simple
      difference equations model and a Time series Susceptible Infectious Recovered
      (TSIR) model) to estimate fortnightly values of a contact parameter (the per
      capita rate of effective contact between two specific individuals), using GP
      consultation data for chickenpox in England and Wales from 1967-2008. RESULTS:
      The estimated contact parameters were 22-31% lower during the summer holiday than
      during termtime. The relationship between the contact parameter and the school
      calendar did not change markedly over the years analysed. CONCLUSIONS: In England
      and Wales, reductions in contact between children during the school summer
      holiday lead to a reduction in the transmission of VZV. These estimates are
      relevant for predicting how closing schools and nurseries may affect an outbreak
      of an emerging respiratory-spread pathogen.

PMID- 24932997
TI  - Outcomes of programs serving mothers with psychiatric disabilities and their
      young children: a multisite case file abstraction study.
AB  - OBJECTIVE: This multisite study examined outcomes of mothers with mental
      illnesses receiving integrated clinical, rehabilitation, and parenting services
      for their preschool-age children. Mothers' outcomes included independent living
      and employment status, custody loss and reunification, psychiatric
      hospitalization, and substance abuse. METHOD: Retrospective case file abstraction
      yielded data regarding 104 mothers served over 12-month periods during 1995-1999
      at 4 programs located in 3 different states. Multivariable logistic regression
      (MLR) analysis explored associations between outcomes and predictors from prior
      research, controlling for study site. RESULTS: During their first 12 months of
      program participation, significant increases were found in the proportions of
      mothers employed and living independently. Significant decreases were noted in
      the proportion of mothers abusing substances. Although 10% of the women served
      lost formal custody during their first year of participation, 22% were reunited
      with 1 or more children. In MLR analysis, mothers who abused substances were more
      likely to have experienced childhood sexual abuse and custody loss; those who
      were psychiatrically hospitalized were more likely to have abused substances,
      lost custody of 1 or more children, and had more disabling forms of mental
      illness; and those who lost custody of 1 or more children were more likely to
      have experienced a psychiatric hospitalization and less likely to be residing
      with 3 or more children. CONCLUSIONS: Programs for mothers with mental illness
      and their preschool children address service needs in an integrated fashion that
      appears to improve clinical and rehabilitation outcomes, while preventing custody
      loss and supporting reunification.

PMID- 24932993
TI  - Malformations of cortical development: clinical features and genetic causes.
AB  - Malformations of cortical development are common causes of developmental delay
      and epilepsy. Some patients have early, severe neurological impairment, but
      others have epilepsy or unexpected deficits that are detectable only by
      screening. The rapid evolution of molecular biology, genetics, and imaging has
      resulted in a substantial increase in knowledge about the development of the
      cerebral cortex and the number and types of malformations reported. Genetic
      studies have identified several genes that might disrupt each of the main stages
      of cell proliferation and specification, neuronal migration, and late cortical
      organisation. Many of these malformations are caused by de-novo dominant or X
      linked mutations occurring in sporadic cases. Genetic testing needs accurate
      assessment of imaging features, and familial distribution, if any, and can be
      straightforward in some disorders but requires a complex diagnostic algorithm in
      others. Because of substantial genotypic and phenotypic heterogeneity for most of
      these genes, a comprehensive analysis of clinical, imaging, and genetic data is
      needed to properly define these disorders. Exome sequencing and high-field MRI
      are rapidly modifying the classification of these disorders. 

PMID- 24932998
TI  - JAK2, STAT3 and SOCS3 gene expression in women with and without breast cancer.
AB  - INTRODUCTION: Breast cancer is a disease that arises from the accumulation of
      alterations in the genome of cells that make up the mammary gland. The Janus
      kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3)
      signaling pathway has been reported to participate in the development of breast
      cancer and is activated by adipocytokines such as leptin, which are elevated in
      obesity. In contrast, alterations in suppressor of cytokine signaling 3 (SOCS3)
      gene expression have been found in patients with decreased breast cancer
      metastasis. OBJECTIVE: The current study sought to identify whether JAK2, STAT3
      and SOCS3 gene expression is associated with body mass index (BMI) and breast
      cancer. METHODS: This was a cross-sectional prospective study. JAK2, STAT3 and
      SOCS3 gene expression levels were determined using RT-qPCR from the biopsies of
      26 patients with breast cancer and 43 patients with benign breast lesions. We
      compared the expression of these genes, relative to the housekeeping genes, ACTB
      and GAPDH, against BMI, clinical stage and immunohistochemistry. RESULTS: STAT3
      gene expression was increased in breast cancer patients (p<=0.001; AUC=0.65; AUC
      95% CI: 0.5-0.8), and SOCS3 expression was decreased in obese patients with
      benign breast lesions (p<=0.001; AUC=0.51; AUC 95% CI: 0.36-0.65). With regard to
      the clinical stage, there were significant differences in STAT3 gene expression
      between stage II and III (p<=0.011) and stage II and IV (p<=0.033) breast
      cancers. Among all women, there was a positive correlation between JAK2 and STAT3
      expression (R=0.493, p=0.000). In addition, breast cancers that were negative for
      HER2 were associated with JAK2 and SOCS3 (R=0.645, p=0.003). CONCLUSION: High
      levels of STAT3 expression were associated with early stages of breast cancer
      development and patients in the control group with obesity showed higher
      expression of SOCS3 regarding overweight.

PMID- 24932999
TI  - Exploring the molecular mechanism of acute heat stress exposure in broiler
      chickens using gene expression profiling.
AB  - The process of heat regulation is complex and its exact molecular mechanism is
      not fully understood. In this study, to investigate the global gene regulation
      response to acute heat exposure, gene microarrays were exploited to analyze the
      effects of heat stress on three tissues (brain, liver, leg muscle) of the yellow
      broiler chicken (Gallus gallus). We detected 166 differentially expressed genes
      (DEGs) in the brain, 219 in the leg muscle and 317 in the liver. Six of these
      genes were differentially expressed in all three tissues and were validated by
      qRT-PCR, and included heat shock protein genes (HSPH1, HSP25), apoptosis-related
      genes (RB1CC1, BAG3), a cell proliferation and differentiation-related gene (ID1)
      and the hunger and energy metabolism related gene (PDK). All these genes might be
      important factors in chickens suffering from heat stress. We constructed gene co
      expression networks using the DEGs of the brain, leg muscle and liver and two,
      four and two gene co-expression modules were identified in these tissues,
      respectively. Functional enrichment of these gene modules revealed that various
      functional clusters were related to the effects of heat stress, including those
      for cytoskeleton, extracellular space, ion binding and energy metabolism. We
      concluded that these genes and functional clusters might be important factors in
      chickens under acute heat stress. Further in-depth research on the newly
      discovered heat-related genes and functional clusters is required to fully
      understand their molecular functions in thermoregulation. 

PMID- 24933000
TI  - Challenges in assessing pathogenicity based on frequency of variants in mismatch
      repair genes: an extreme case of a MSH2 variant and a meta-analysis.
AB  - The clinical interpretation of variants in mismatch repair (MMR) genes associated
      with Lynch syndrome can be confusing when the functional nature of the variant is
      not clearly defined. We report an extreme case where a polymorphism in the MSH2
      gene which had a low minor allele frequency, was misclassified as a mutation
      based on low evidential methods in the database and previous publications. We
      expanded this experience to perform a systematic meta-analysis in order to
      investigate other variants that have potentially been misclassified. Our results
      suggested that the interpretation of pathogenicity should be more cautious and
      emphasized the need for solid validation through multiple analyses including
      functional analysis for variants in MMR genes. 

PMID- 24933001
TI  - GC constituents and relative codon expressed amino acid composition in
      cyanobacterial phycobiliproteins.
AB  - The genomic as well as structural relationship of phycobiliproteins (PBPs) in
      different cyanobacterial species are determined by nucleotides as well as amino
      acid composition. The genomic GC constituents influence the amino acid
      variability and codon usage of particular subunit of PBPs. We have analyzed 11
      cyanobacterial species to explore the variation of amino acids and causal
      relationship between GC constituents and codon usage. The study at the first,
      second and third levels of GC content showed relatively more amino acid
      variability on the levels of G3+C3 position in comparison to the first and second
      positions. The amino acid encoded GC rich level including G rich and C rich or
      both correlate the codon variability and amino acid availability. The fluctuation
      in amino acids such as Arg, Ala, His, Asp, Gly, Leu and Glu in alpha and beta
      subunits was observed at G1C1 position; however, fluctuation in other amino acids
      such as Ser, Thr, Cys and Trp was observed at G2C2 position. The coding selection
      pressure of amino acids such as Ala, Thr, Tyr, Asp, Gly, Ile, Leu, Asn, and Ser
      in alpha and beta subunits of PBPs was more elaborated at G3C3 position. In this
      study, we observed that each subunit of PBPs is codon specific for particular
      amino acid. These results suggest that genomic constraint linked with GC
      constituents selects the codon for particular amino acids and furthermore, the
      codon level study may be a novel approach to explore many problems associated
      with genomics and proteomics of cyanobacteria. 

PMID- 24933003
TI  - The impact of respiratory gating on lung dosimetry in stereotactic body
      radiotherapy for lung cancer.
AB  - The purpose of this study was to evaluate the impacts of respiratory gating and
      different gating windows (GWs) on lung dosimetry in stereotactic body
      radiotherapy (SBRT) for lung cancer. Gated SBRT plans were developed using the
      four-dimensional computed tomography data from 17 lung cancer patients treated
      with SBRT. Using amplitude-based end-exhalation gating, we established 2 fixed
      GWs with approximate duty cycles of 50% (50% GW) and 25% (25% GW), respectively,
      for this study. For highly mobile tumors (3D mobility > 10 mm), additional
      benefits in lung-dose reductions were achieved with the 25% GW, as a result of
      inadequate mobility and planning target volume reductions obtained with the 50%
      GW. In these tumors, the absolute differences compared to the non-gated and 50%
      gated plans, were 0.5 Gy and 0.33 Gy for the mean lung dose and 1.11% and 0.71%
      for the V20, respectively. Dosimetric benefits were achieved with the 50% GW,
      compared with the non-gated plan, for tumors with both low mobility and small
      volume (gross tumor volume <= 10 cc). Among the identified predictive factors of
      dosimetric benefits, the lateral distance from midspinal canal and the motion
      range in anterior-posterior direction might be stronger factors because of their
      correlations with many of the lung-dose parameters and greater predictive
      capacity. The results of the present study might facilitate the selection of
      appropriate patients and the optimal GW according to the tumor characteristics
      for gated lung SBRT. 

PMID- 24933002
TI  - Common variants of xeroderma pigmentosum genes and prostate cancer risk.
AB  - The genetic basis of prostate cancer (PC) is complex and appears to involve
      multiple susceptibility genes. A number of studies have evaluated a possible
      correlation between several NER gene polymorphisms and PC risk, but most of them
      evaluated only single SNPs among XP genes and the results remain inconsistent.
      Out of 94 SNPs located in seven XP genes (XPA-XPG) a total of 15 SNPs were
      assayed in 720 unselected patients with PC and compared to 1121 healthy adults.
      An increased risk of disease was associated with the XPD SNP, rs1799793
      (Asp312Asn) AG genotype (OR=2.60; p<0.001) and with the AA genotype (OR=531;
      p<0.0001) compared to the control population. Haplotype analysis of XPD revealed
      one protective haplotype and four associated with an increased disease risk,
      which showed that the A allele (XPD rs1799793) appeared to drive the main effect
      on promoting prostate cancer risk. Polymorphism in XPD gene appears to be
      associated with the risk of prostate cancer. 

PMID- 24933004
TI  - Balance as a measurement of fatigue in postcall residents.
AB  - OBJECTIVES/HYPOTHESIS: To determine the degree to which balance is impaired by
      fatigue in postcall medical residents and to assess the validity of posturography
      in quantifying that impairment. STUDY DESIGN: Prospective study. METHODS: Medical
      residents underwent the following tests before and immediately after overnight
      call: 1) computerized dynamic posturography (CDP) using the Equitest force
      platform (Natus Medical Inc., Clackamas, OR); 2) Clinical Test of Sensory
      Interaction and Balance, in which the residents stood on a compliant foam mat
      with closed eyes and flexed and extended their necks; 3) a computerized reaction
      time test (available at www.humanbenchmark.com). All tests were performed before
      and after call at approximately the same time of day to exclude circadian rhythm
      influence on fatigue. The residents also completed questionnaires, including the
      Stanford Sleepiness Scale, describing their level of fatigue before and after
      call. RESULTS: A statistically significant difference was found between a
      resident's pre- and postcall test with regard to reaction time (P = .01),
      Stanford Sleepiness Scale score (P = .001), and preference for the visual system
      as measured by CDP (P = .05). Linear regression analysis showed a statistically
      significant relationship between sleep deprivation and multiple performance
      variables measured by CDP. CONCLUSIONS: With the growing attention paid to
      resident duty hours, there is an increasing need for research involving fatigue
      and practical ways to measure it. This study shows that residents who are
      measurably fatigued (both objectively and subjectively) may have difficulty
      utilizing vestibular input during quiet standing but can compensate by means of
      somatosensory and visual input. LEVEL OF EVIDENCE: NA.

PMID- 24933005
TI  - Proteomic profiling of chikungunya virus-infected human muscle cells: reveal the
      role of cytoskeleton network in CHIKV replication.
AB  - Chikungunya virus (CHIKV) is an arthropod-borne, positive-sense, single-stranded
      RNA virus belonging to genus Alphavirus and family Togaviridae. The clinical
      manifestations developed upon CHIKV-infection include fever, myositis, arthralgia
      and maculopapular rash. Thus, the re-emergence of CHIKV has posed serious health
      threats worldwide. Due to the fact that myositis is induced upon CHIKV-infection,
      we sought to understand the dynamic proteomic regulation in SJCRH30, a human
      rhabdomyosarcoma cell line, to gain insights on CHIKV pathogenesis. Two
      dimensional gel electrophoresis (2DE) in combination of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to
      profile differential cellular proteins expression in CHIKV-infected SJCRH30
      cells. 2DE analysis on CHIKV-infected cells has revealed 44 protein spots. These
      spots are found to be involved in various biological pathways such as
      biomolecules synthesis and metabolism, cell signaling and cellular
      reorganization. siRNA-mediated gene silencing on selected genes has elucidated
      the biological significance of these gene-translated host proteins involved in
      CHIKV-infection. More importantly, the interaction of vimentin with non
      structural protein (nsP3) of CHIKV was shown, suggesting the role played by
      vimentin during CHIKV replication by forming an anchorage network with the CHIKV
      replication complexes (RCs). BIOLOGICAL SIGNIFICANCE: Chikungunya virus (CHIKV)
      is a re-emerging virus that has caused various disease outbreaks in Africa and
      Asia. The clinical symptoms of CHIKV-infection include fever, skin rash,
      recurrent joint paint, and myositis. Neuronal implications and death may be
      resulted from the severe viral infection. Up to date, there are no effective
      treatments and vaccines against CHIKV-infection. More importantly, little is
      known about the differential regulation of host proteins upon CHIKV infection,
      hence deciphering the viral-host cell interactions during viral infection provide
      critical information on our understanding on the mechanisms of virus infection
      and its dependency of host proteins for replication. In light of the muscle
      related clinical manifestations of myositis resulting from CHIKV-infection, human
      rhabdomyosarcoma cells, SJCRH30 were utilized in this protein profiling study, in
      order to decipher the pathogenesis of CHIKV. This study has identified an arrays
      of host proteins that are differentially regulated upon CHIKV infection including
      that of the cytoskeletal protein, vimentin that plays significant role in aiding
      the replication of CHIKV within the host cells through 2DE assay.
      Immunofluorescence assay further shows that the novel interaction between
      cytoskeleton structure and CHIKV replication complex by forming an intercalating
      network around the replication complexes and facilitating various stages of the
      virus life cycle. This novel finding has inevitably led to a deeper understanding
      of CHIKV pathogenesis in revealing the importance of host proteins during CHIKV
      replication, as well as contributing to the development of specific antiviral
      strategies against this medically important viral pathogen.

PMID- 24933006
TI  - Phospho-proteomic analysis of developmental reprogramming in the moss
      Physcomitrella patens.
AB  - One of the most common post-translational modifications is protein
      phosphorylation, which controls many activities of plant life. However, its role
      in the reprogramming of developmental pathways of plant cells remains elusive.
      Here, using Physcomitrella patens, we characterize the phospho-proteome for
      protonemata, protoplasts made therefrom, and protoplasts regenerated for 2d.
      Through a titanium dioxide (TiO2)-based phospho-peptide enrichment method and
      liquid chromatography-tandem mass spectrometry (LC-MS/MS), more than 2000 phospho
      proteins were identified. Among the 519 proteins with functional annotation in
      fresh protoplasts and protoplasts regenerated for 2d, proteins involved in
      epigenetic modification, post-transcriptional gene regulation, hormone signal
      transduction, and meristem maintenance have been previously reported to be
      important for developmental reprogramming. Several novel transcription factors
      including SWI/SNF complex protein, SNF2 family protein and MADS-domain
      transcription factor appear to be important in developmental reprogramming plant
      cells. Phosphorylation of marker proteins such as somatic embryogenesis receptor
      kinase and NAC transcription factor, suggests that this post-translational
      modification is vital for the cell's ability to adjust its developmental program.
      Together, our study presents a more complete understanding of the plant cell's
      developmental reprogramming. BIOLOGICAL SIGNIFICANCE: Protoplast regeneration is
      an ideal model system for investigating developmental reprogramming in plants.
      Here, for Physcomitrella patens, we characterize the phospho-proteome for
      protonemata, protoplasts made therefrom, and for protonemata regenerated from the
      protoplasts for 2d. Among the 519 proteins with functional annotation in fresh
      protoplasts and protoplasts regenerated for 2d, proteins involved in epigenetic
      modification, post-transcriptional gene regulation, hormone signal transduction,
      and meristem maintenance have been reported to be important for expression of
      developmental reprogramming. Together, our study presents a more complete
      understanding of the plant cell's developmental reprogramming.

PMID- 24933007
TI  - Abnormal hepatocellular mitochondria in methylmalonic acidemia.
AB  - Methylmalonic acidemia (MMA) is one of the most frequently encountered forms of
      branched-chain organic acidemias. Biochemical abnormalities seen in some MMA
      patients, such as lactic acidemia and increased tricarboxylic acid cycle
      intermediate excretion, suggest mitochondrial dysfunction. In order to
      investigate the possibility of mitochondrial involvement in MMA, we examined
      liver tissue for evidence of mitochondrial ultrastructural abnormalities. Five
      explanted livers obtained from MMA mut(0) patients undergoing liver
      transplantation were biopsied. All patients had previous episodes of metabolic
      acidosis, lactic acidemia, ketonuria, and hyperammonemia. All biopsies revealed a
      striking mitochondriopathy by electron microscopy. Mitochondria were markedly
      variable in size, shape, and conformation of cristae. The inner matrix appeared
      to be greatly expanded and the cristae were diminutive and disconnected. No
      crystalloid inclusions were noted. This series clearly documents extensive
      mitochondrial ultrastructure abnormalities in liver samples from MMA patients
      undergoing transplantation, providing pathological evidence for mitochondrial
      dysfunction in the pathophysiology of MMA mut(0). Considering the trend to
      abnormally large mitochondria, the metabolic effects of MMA may restrict
      mitochondrial fission or promote fusion. The correlation between mitochondrial
      dysfunction and morphological abnormalities in MMA may provide insights for
      better understanding and monitoring of optimized or novel therapeutic strategies.

PMID- 24933009
TI  - Response to Snijders et al.

PMID- 24933008
TI  - Himalayan-Tibetan plateau uplift drives divergence of polyploid poppies:
      Meconopsis Viguier (Papaveraceae).
AB  - Meconopsis Viguier (Papaveraceae) is an iconic genus of alpine forbs that
      includes medicinal and ornamental species. This study extends previous
      phylogenetic analyses of Meconopsis, using ITS sequences representing all the
      major Meconopsis clades. Phenotypic traits are also analysed for all described
      species. Our results show that Meconopsis evolved as a >= octaploid clade, with
      considerable interior structure reflecting further changes in ploidy levels as
      well as phenotypic differentiation. We support the exclusion of a few species as
      Cathcartia or Papaver, making Meconopsis a Tibetan region clade. Based on average
      rates of nucleotide substitution in angiosperm herbs we estimate that the
      Meconopsis clade diverged from the Meconella clade of Papaver approximately 16.6
      Ma. This is soon after the 'hard' collision of the Indian continent with Asia
      caused uplift of the Himalaya and Hengduan ranges, greatly extended the Tibetan
      plateau, and initiated monsoonal climates. Eight major clades within Meconopsis
      are well supported and these correspond closely to previously recognised subgenus
      groups. However, the relationship among the clades is poorly resolved, probably
      because they diverged rapidly ~15-11 Ma. Two of these clades are ~dodecaploid but
      appear to have originated independently. The eight clades have distinct
      distributions, variously associated with the Himalaya, the eastern Plateau and
      Hengduan ranges. Some Meconopsis species were not monophyletic, suggesting that a
      combination of multilocus molecular and phenotypic traits is required when
      defining and revising species. 

PMID- 24933010
TI  - Nasal NO, high-speed video microscopy, electron microscopy, and genetics: a
      primary ciliary dyskinesia puzzle to complete.

PMID- 24933011
TI  - Multi-Channel neurodegenerative pattern analysis and its application in
      Alzheimer's disease characterization.
AB  - Neuroimaging has played an important role in non-invasive diagnosis and
      differentiation of neurodegenerative disorders, such as Alzheimer's disease and
      Mild Cognitive Impairment. Various features have been extracted from the
      neuroimaging data to characterize the disorders, and these features can be
      roughly divided into global and local features. Recent studies show a tendency of
      using local features in disease characterization, since they are capable of
      identifying the subtle disease-specific patterns associated with the effects of
      the disease on human brain. However, problems arise if the neuroimaging database
      involved multiple disorders or progressive disorders, as disorders of different
      types or at different progressive stages might exhibit different degenerative
      patterns. It is difficult for the researchers to reach consensus on what brain
      regions could effectively distinguish multiple disorders or multiple progression
      stages. In this study we proposed a Multi-Channel pattern analysis approach to
      identify the most discriminative local brain metabolism features for
      neurodegenerative disorder characterization. We compared our method to global
      methods and other pattern analysis methods based on clinical expertise or
      statistics tests. The preliminary results suggested that the proposed Multi
      Channel pattern analysis method outperformed other approaches in Alzheimer's
      disease characterization, and meanwhile provided important insights into the
      underlying pathology of Alzheimer's disease and Mild Cognitive Impairment. 

PMID- 24933012
TI  - Learning curve and long-term outcomes of laparoscopy-assisted distal gastrectomy
      for gastric cancer.
AB  - OBJECTIVE: To discuss the learning curve of laparoscopy-assisted distal
      gastrectomy (LADG) with lymph node dissection and the oncological results and
      long-term outcomes of different periods in the learning stage. PATIENTS AND
      METHODS: One hundred twenty-four patients with gastric cancer who received LADG
      with lymph node dissection from January 2004 to December 2009 were
      retrospectively reviewed and analyzed. They were divided into three groups (A-C)
      according to different operative date: 41 were in Group A (early), 41 in Group B
      (middle), and 42 in Group C (laer). There were no significant statistical
      differences among the three groups with respect to age, gender, early/advanced
      gastric cancer, Union for International Cancer Control stage, and lymph node
      dissection. Then the following items were compared in these groups: operative
      time, blood loss, number of lymph nodes harvested, postoperative complications,
      postoperative hospital stay, and long-term survival. RESULTS: The operative time
      in Group A (235.0+/-50.3 minutes) was significantly longer than in Groups B
      (201.7+/-39.6 minutes) and C (199.0+/-44.7 minutes), but there was no significant
      difference between Groups B and C. The harvest of lymph nodes from Group A
      (11.0+/-5.5) was significantly less than from Groups B (16.3+/-9.2) and C (17.2+/
      8.7), but there was no significant difference between Groups B and C. The
      postoperative hospital stay and complications, overall survival, and disease-free
      survival showed no difference among the three groups. CONCLUSIONS: The learning
      curve of gastrointestinal surgeons with experience of laparoscopic operation is
      about 40 cases. The oncological principles and long-term outcomes were not
      sacrificed during the learning stage.

PMID- 24933013
TI  - From childhood trauma to elevated C-reactive protein in adulthood: the role of
      anxiety and emotional eating.
AB  - OBJECTIVE: Childhood trauma is known to be related to inflammatory processes in
      adulthood, but underlying psychological/behavioral mechanisms have not been fully
      characterized. To investigate associations between childhood trauma and
      inflammation (indexed by C-reactive protein [CRP]), we used a structural equation
      modeling approach on a subsample of the Midlife in the United States biomarker
      project. METHODS: Participants included 687 men and women without history of
      cancer, diabetes, cardiovascular disease, or stroke who completed a physical
      examination and extensive questionnaires and provided blood. To test for sex
      differences, we held as many parameters invariant across sexes as possible while
      still retaining good model fit. RESULTS: Tests of direct and indirect effects
      revealed that childhood trauma was significantly associated with elevated CRP,
      via elevated body mass index (BMI; p < .001). This relationship was mediated by a
      broad latent measure of distress, which was associated with using food as a
      coping mechanism. Men and women differed in reported levels of physical abuse,
      sexual abuse, and physical neglect. Compared with men, women showed a stronger
      association between BMI and CRP, whereas men had a stronger association between
      use of food to cope and elevated BMI. CONCLUSIONS: Our results are consistent
      with a model in which childhood trauma is associated with elevated CRP, a
      relationship associated with stress reactivity and compensatory emotional eating.
      Men and women may experience trauma in qualitatively distinct patterns but share
      many vulnerabilities, which can lead to elevated health risks. Emotional eating
      may be an important target for intervention in this population.

PMID- 24933014
TI  - Personality facets and all-cause mortality among Medicare patients aged 66 to 102
      years: a follow-on study of Weiss and Costa (2005).
AB  - OBJECTIVE: To investigate associations between personality facets and survival
      during an 8-year follow-up. METHODS: In 597 Medicare recipients (age, 66-102
      years) followed up for approximately 8 years, personality domains and facets were
      assessed using the Revised NEO Personality Inventory (NEO-PI-R). This study
      builds on a previous study which used proportional hazards regression to test
      whether the NEO-PI-R factor and selected facet scores were associated with
      mortality risk. That study revealed that the neuroticism facet impulsiveness,
      agreeableness facet straightforwardness, and conscientiousness facet self
      discipline were related to lower risk during 4 years of follow-up. We extended
      the follow-up period by 4 years, examined all 30 facets, and used accelerated
      failure time modeling as an additional analytic approach. Unlike proportional
      hazards regression, accelerated failure time modeling permits inferences about
      the median survival length conferred by predictors. Each facet was tested in a
      model that included health-related covariates and NEO-PI-R factor scores for
      dimensions that did not include that facet. RESULTS: Over the 8-year follow-up
      period, impulsiveness was not significant, each standard deviation of
      straightforwardness was associated with an 11% increase in median survival time
      and, when dichotomized, higher self-discipline was associated with a 34% increase
      in median survival time. Each standard deviation of altruism, compliance, tender
      mindedness, and openness to fantasy was associated with a 9% to 11% increase in
      median survival time. CONCLUSIONS: After extending the follow-up period from 4 to
      8 years, self-discipline remained a powerful predictor of survival and facets
      associated with imagination, generosity, and higher-quality interpersonal
      interactions become increasingly important.

PMID- 24933015
TI  - Cisplatin loaded methoxy poly (ethylene glycol)-block-Poly (L-glutamic acid-co-L
      Phenylalanine) nanoparticles against human breast cancer cell.
AB  - Cisplatin (cis-diaminodichloroplatinum, CDDP) loaded methoxy poly (ethylene
      glycol)-block-poly (glutamic acid-co-phenyl alanine) [mPEG-b-P (Glu10 -co-Phe10 )
      (PGlu10 ) and mPEG-b-P (Glu20 -co-Phe10 ) (PGlu20 )] nanoparticles with two
      different formulations (CDDP/PGlu10 and CDDP/PGlu20 ) are successfully developed
      in uniformly sizes. In 190 h, the CDDP/PGlu10 shows 30% release at physiological
      pH and 39% at lysosomal pH. Similarly, the CDDP/PGlu20 shows 60% release at
      physiological pH and 90% release at lysosomal pH. The sustained and controlled
      release of both formulations evidences the in vitro longevity of the
      nanoparticles. The cell proliferation inhibition of nanoparticles against human
      breast cancer cell line ZR-75-30 is dose and time dependent. Both CDDP/PGlu10 and
      CDDP/PGlu20 show excellent hemo compatibility as evaluated by hemolysis
      experiments. The in vivo fate of CDDP and CDDP loaded nanoparticles are evaluated
      by pharmacokinetics studies. Free CDDP underwgoes instant platinum concentration
      decrease after intravenous administration with 1.0 wt% left in 24 h while the
      CDDP loaded nanoparticles show prolonged blood circulation time with 5 wt%
      (CDDP/PGlu20 ) to 14 wt% (CDDP/PGlu10 ) left in 24 h. This prolonged blood
      circulation of CDDP loaded nanoparticles makes them as promising nanocarriers for
      tumor targeting delivery. 

PMID- 24933016
TI  - Using information from historical high-throughput screens to predict active
      compounds.
AB  - Modern high-throughput screening (HTS) is a well-established approach for hit
      finding in drug discovery that is routinely employed in the pharmaceutical
      industry to screen more than a million compounds within a few weeks. However, as
      the industry shifts to more disease-relevant but more complex phenotypic screens,
      the focus has moved to piloting smaller but smarter chemically/biologically
      diverse subsets followed by an expansion around hit compounds. One standard
      method for doing this is to train a machine-learning (ML) model with the chemical
      fingerprints of the tested subset of molecules and then select the next compounds
      based on the predictions of this model. An alternative approach would be to take
      advantage of the wealth of bioactivity information contained in older (full-deck)
      screens using so-called HTS fingerprints, where each element of the fingerprint
      corresponds to the outcome of a particular assay, as input to machine-learning
      algorithms. We constructed HTS fingerprints using two collections of data: 93 in
      house assays and 95 publicly available assays from PubChem. For each source, an
      additional set of 51 and 46 assays, respectively, was collected for testing.
      Three different ML methods, random forest (RF), logistic regression (LR), and
      naive Bayes (NB), were investigated for both the HTS fingerprint and a chemical
      fingerprint, Morgan2. RF was found to be best suited for learning from HTS
      fingerprints yielding area under the receiver operating characteristic curve
      (AUC) values >0.8 for 78% of the internal assays and enrichment factors at 5%
      (EF(5%)) >10 for 55% of the assays. The RF(HTS-fp) generally outperformed the LR
      trained with Morgan2, which was the best ML method for the chemical fingerprint,
      for the majority of assays. In addition, HTS fingerprints were found to retrieve
      more diverse chemotypes. Combining the two models through heterogeneous
      classifier fusion led to a similar or better performance than the best individual
      model for all assays. Further validation using a pair of in-house assays and data
      from a confirmatory screen--including a prospective set of around 2000 compounds
      selected based on our approach--confirmed the good performance. Thus, the
      combination of machine-learning with HTS fingerprints and chemical fingerprints
      utilizes information from both domains and presents a very promising approach for
      hit expansion, leading to more hits. The source code used with the public data is
      provided.

PMID- 24933018
TI  - The effects of daily supplementation of Dendrobium huoshanense polysaccharide on
      ethanol-induced subacute liver injury in mice by proteomic analysis.
AB  - Polysaccharides isolated from edible Dendrobium huoshanense have been shown to
      possess a hepatoprotection function for selenium- and carbon tetrachloride
      induced liver injury. In this study, we investigated the preventive effects of
      daily supplementation with an homogeneous polysaccharide (DHP) purified from D.
      huoshanense on ethanol-induced subacute liver injury in mice and its potential
      mechanisms in liver protection by a proteomic approach. DHP was found to
      effectively depress the increased ratio of liver weight to body weight, reduce
      the elevated levels of serum aspartate aminotransferase, total cholesterol, total
      bilirubin and low density lipoprotein, and alleviate hepatic steatosis in mice
      with ethanol-induced subacute liver injury. Hepatic proteomics analysis performed
      by two-dimensional difference gel electrophoresis (2D-DIGE) coupled with matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI
      TOF/TOF-MS) revealed that cystathionine beta-synthase (Cbs) and D-lactate
      dehydrogenase (Ldhd) were two key proteins regulated by daily DHP intervention,
      which may assist in correcting the abnormal hepatic methionine metabolism pathway
      and decreasing the level of hepatic methylglyoxal generated from disordered
      metabolic pathways caused by ethanol. Our data suggest that DHP can protect liver
      function from alcoholic injury with complicated molecular mechanisms involving
      regulation of Cbs and Ldhd.

PMID- 24933017
TI  - The analytic bilinear discrimination of single-trial EEG signals in rapid image
      triage.
AB  - The linear discriminant analysis (LDA) method is a classical and commonly
      utilized technique for dimensionality reduction and classification in brain
      computer interface (BCI) systems. Being a first-order discriminator, LDA is
      usually preceded by the feature extraction of electroencephalogram (EEG) signals,
      as multi-density EEG data are of second order. In this study, an analytic
      bilinear classification method which inherits and extends LDA is proposed. This
      method considers 2-dimentional EEG signals as the feature input and performs
      classification using the optimized complex-valued bilinear projections. Without
      being transformed into frequency domain, the complex-valued bilinear projections
      essentially spatially and temporally modulate the phases and magnitudes of slow
      event-related potentials (ERPs) elicited by distinct brain states in the sense
      that they become more separable. The results show that the proposed method has
      demonstrated its discriminating capability in the development of a rapid image
      triage (RIT) system, which is a challenging variant of BCIs due to the fast
      presentation speed and consequently overlapping of ERPs. 

PMID- 24933019
TI  - In silico identification of plant miRNAs in mammalian breast milk exosomes--a
      small step forward?
AB  - MicroRNAs (miRNAs) are a class of small RNA molecules that regulate gene
      expression by inhibiting the protein translation or targeting the mRNA cleavage.
      They play many important roles in living organism cells; however, the knowledge
      on miRNAs functions has become more extensive upon their identification in
      biological fluids and recent reports on plant-origin miRNAs abundance in human
      plasma and serum. Considering these findings, we performed a rigorous
      bioinformatics analysis of publicly available, raw data from high-throughput
      sequencing studies on miRNAs composition in human and porcine breast milk
      exosomes to identify the fraction of food-derived miRNAs. Several processing and
      filtering steps were applied to increase the accuracy, and to avoid false
      positives. Through aforementioned analysis, 35 and 17 miRNA species, belonging to
      25 and 11 MIR families, were identified, respectively. In the human samples the
      highest abundance levels yielded the ath-miR166a, pab-miR951, ptc-miR472a and bdi
      miR168, while in the porcine breast milk exosomes, the zma-miR168a, zma-miR156a
      and ath-miR166a have been identified in the largest amounts. The consensus
      prediction and annotation of potential human targets for select plant miRNAs
      suggest that the aforementioned molecules may interact with mRNAs coding several
      transcription factors, protein receptors, transporters and immune-related
      proteins, thus potentially influencing human organism. Taken together, the
      presented analysis shows proof of abundant plant miRNAs in mammal breast milk
      exosomes, pointing at the same time to the new possibilities arising from this
      discovery. 

PMID- 24933021
TI  - Survey of the crayfish plague pathogen presence in the Netherlands reveals a new
      Aphanomyces astaci carrier.
AB  - North American crayfish species as hosts for the crayfish plague pathogen
      Aphanomyces astaci contribute to the decline of native European crayfish
      populations. At least six American crayfish species have been reported in the
      Netherlands but the presence of this pathogenic oomycete with substantial
      conservational impact has not yet been confirmed in the country. We evaluated A.
      astaci prevalence in Dutch populations of six alien crustaceans using species
      specific quantitative PCR. These included three confirmed crayfish carriers
      (Orconectes limosus, Pacifastacus leniusculus, Procambarus clarkii), two recently
      introduced but yet unstudied crayfish (Orconectes cf. virilis, Procambarus cf.
      acutus), and a catadromous crab Eriocheir sinensis. Moderate levels of infection
      were observed in some populations of O. limosus and P. leniusculus. Positive
      results were also obtained for E. sinensis and two Dutch populations of O. cf.
      virilis. English population of the latter species was also found infected,
      confirming this taxon as another A. astaci carrier in European waters. In
      contrast, Dutch P. clarkii seem only sporadically infected, and the pathogen was
      not yet detected in P. cf. acutus. Our study is the first confirmation of
      crayfish plague infections in the Netherlands and demonstrates substantial
      variation in A. astaci prevalence among potential hosts within a single region, a
      pattern possibly linked to their introduction history and coexistence. 

PMID- 24933020
TI  - An ecosystem-based approach to assess the status of a Mediterranean ecosystem,
      the Posidonia oceanica seagrass meadow.
AB  - Biotic indices, which reflect the quality of the environment, are widely used in
      the marine realm. Sometimes, key species or ecosystem engineers are selected for
      this purpose. This is the case of the Mediterranean seagrass Posidonia oceanica,
      widely used as a biological quality element in the context of the European Union
      Water Framework Directive (WFD). The good quality of a water body and the
      apparent health of a species, whether or not an ecosystem engineer such as P.
      oceanica, is not always indicative of the good structure and functioning of the
      whole ecosystem. A key point of the recent Marine Strategy Framework Directive
      (MSFD) is the ecosystem-based approach. Here, on the basis of a simplified
      conceptual model of the P. oceanica ecosystem, we have proposed an ecosystem
      based index of the quality of its functioning, compliant with the MSFD
      requirements. This index (EBQI) is based upon a set of representative functional
      compartments, the weighting of these compartments and the assessment of the
      quality of each compartment by comparison of a supposed baseline. The index well
      discriminated 17 sites in the north-western Mediterranean (French Riviera,
      Provence, Corsica, Catalonia and Balearic Islands) covering a wide range of human
      pressure levels. The strong points of the EBQI are that it is easy to implement,
      non-destructive, relatively robust, according to the selection of the
      compartments and to their weighting, and associated with confidence indices that
      indicate possible weakness and biases and therefore the need for further field
      data acquisition. 

PMID- 24933022
TI  - First report on vertical transmission of a plasmid DNA in freshwater prawn,
      Macrobrachium rosenbergii.
AB  - Outbreak of WSSV disease is one of the major stumbling blocks in shrimp
      aquaculture. DNA vaccines have shown potential for mass scale vaccination owing
      to their stability, cost effectiveness and easy maintenance. Development of
      economically feasible delivery strategies remains to be a major challenge. This
      study demonstrates vertical transmission of a plasmid DNA in a decapod
      Macrobrachium rosenbergii for the first time. Females at three different
      maturation stages (immature, matured and berried) and mature males were injected
      with a plasmid DNA and allowed to spawn with untreated counterparts. Using
      specific primers the plasmid DNA could be amplified from the offspring of all
      groups except that of berried females. For this confirmation genomic DNA was
      isolated from 3 pools of 10 post larvae in each group. This presents an ideal
      strategy to protect young ones at zero stress. 

PMID- 24933023
TI  - The quick extraction of chitin from an epizoic crustacean species (Chelonibia
      patula).
AB  - Chitin was isolated from the shells of Chelonibia patula (barnacle, Crustacea),
      which lives on blue crab epizoically, following a 10-min demineralisation process
      through HCl and a 20-min deproteinisation process through NaOH. Due to the low
      crystalline structure, and mineral-rich and low-protein content of the shells,
      chitin isolation was convenient. It was observed that the shell structure of C.
      patula contains 3.11% chitin per its dry weight. Following characterisation of
      the isolated chitin by using Fourier transform infrared spectroscopy,
      thermogravimetric analysis, X-ray diffractometry, elemental analysis and scanning
      electron microscopy, it was determined that there was close similarity with the
      alpha-chitin isolated from crabs, shrimps and insects in various studies. It was
      observed that chitin was composed of nanofibres with a width of 10-20 nm. It was
      concluded that this was an economically advantageous chitin resource compared
      with crustaceans such as shrimp, crayfish and crab, because it is possible to
      isolate chitin in a significantly shorter time.

PMID- 24933025
TI  - Serum and adipose tissue amino acid homeostasis in the metabolically healthy
      obese.
AB  - A subgroup of obese individuals, referred to as metabolically healthy obese
      (MHO), have preserved insulin sensitivity and a normal lipid profile despite
      being obese. The molecular basis for this improved cardiometabolic profile
      remains unclear. Our objective was to integrate metabolite and gene expression
      profiling to elucidate the molecular distinctions between MHO and metabolically
      unhealthy obese (MUO) phenotypes. A subset of individuals were selected from the
      Diabetes Risk Assessment study and classified into three groups using
      anthropometric and clinical measurements: lean healthy (LH), MHO, and MUO. Serum
      metabolites were profiled using gas chromatography coupled to mass spectrometry.
      Multivariate data analysis uncovered metabolites that differed between groups,
      and these were subsequently validated by capillary electrophoresis coupled to
      mass spectrometry. Subcutaneous adipose tissue (SAT) gene expression profiling
      using microarrays was performed in parallel. Amino acids were the most relevant
      class of metabolites distinguishing MHO from MUO individuals. Serum levels of
      glutamic acid, valine, and isoleucine were positively associated (i.e., LH < MHO
      < MUO) with homeostasis model assessment-insulin resistance (HOMA-IR) and
      glycated hemoglobin (HbA1c) values, while leucine was only correlated with HOMA
      IR. The glutamine-to-glutamic acid ratio and glycine were inversely correlated
      (i.e., LH > MHO > MUO) with HbA1c values. Concomitantly, SAT gene expression
      profiling revealed that genes related to branched-chain amino acid catabolism and
      the tricarboxylic acid cycle were less down-regulated in MHO individuals compared
      to MUO individuals. Together, this integrated analysis revealed that MHO
      individuals have an intermediate amino acid homeostasis compared to LH and MUO
      individuals. 

PMID- 24933026
TI  - From 2,4-dimethoxypyrimidine to 1,3-dimethyluracil: isomerization and
      hydrogenation enthalpies and noncovalent interactions.
AB  - An enthalpic value for the N-methyllactam/O-methyllactim isomerization, in the
      gaseous phase, is reported in this work for the conversion between 2,4
      dimethoxypyrimidine and 1,3-dimethyluracil. For this purpose, the enthalpy of
      formation of 2,4-dimethoxypyrimidine, in the gaseous phase, was obtained
      experimentally combining results from combustion calorimetry and Calvet
      microcalorimetry, and the enthalpy of formation of 1,3-dimethyluracil, in the
      gaseous phase, reported previously in the literature, is also discussed. The
      enthalpy of hydrogenation of 1,3-dimethyluracil is compared with the enthalpy of
      hydrogenation of uracil and interpreted in terms of aromaticity, considering the
      influence of the hyperconjugation and the hindrance of the solvation of the ring
      by the methyl groups. The enthalpy of sublimation of 2,4-dimethoxypyrimidine was
      obtained combining Calvet microcalorimetry and differential scanning calorimetry
      results. This enthalpy is compared with the enthalpy of sublimation of 1,3
      dimethyluracil previously reported in the literature and analyzed herein. From
      the interplay between the experimental results and the theoretical simulation of
      dimers of these molecules, the influence of stereochemical hindrance on the in
      plane intermolecular contacts and aromaticity on the pi...pi interactions is
      analyzed. 

PMID- 24933024
TI  - Denoising MR images using non-local means filter with combined patch and pixel
      similarity.
AB  - Denoising is critical for improving visual quality and reliability of associative
      quantitative analysis when magnetic resonance (MR) images are acquired with low
      signal-to-noise ratios. The classical non-local means (NLM) filter, which
      averages pixels weighted by the similarity of their neighborhoods, is adapted and
      demonstrated to effectively reduce Rician noise without affecting edge details in
      MR magnitude images. However, the Rician NLM (RNLM) filter usually blurs small
      high-contrast particle details which might be clinically relevant information. In
      this paper, we investigated the reason of this particle blurring problem and
      proposed a novel particle-preserving RNLM filter with combined patch and pixel
      (RNLM-CPP) similarity. The results of experiments on both synthetic and real MR
      data demonstrate that the proposed RNLM-CPP filter can preserve small high
      contrast particle details better than the original RNLM filter while denoising MR
      images. 

PMID- 24933027
TI  - Label-free determination of hemodynamic parameters in the microcirculaton with
      third harmonic generation microscopy.
AB  - Determination of blood flow velocity and related hemodynamic parameters is an
      important aspect of physiological studies which in many settings requires
      fluorescent labeling. Here we show that Third Harmonic Generation (THG)
      microscopy is a suitable tool for label-free intravital investigations of the
      microcirculation in widely-used physiological model systems. THG microscopy is a
      non-fluorescent multi-photon scanning technique combining the advantages of label
      free imaging with restriction of signal generation to a focal spot. Blood flow
      was visualized and its velocity was measured in adult mouse cremaster muscle
      vessels, non-invasively in mouse ear vessels and in Xenopus tadpoles. In
      arterioles, THG line scanning allowed determination of the flow pulse velocity
      curve and hence the heart rate. By relocating the scan line we obtained velocity
      profiles through vessel diameters, allowing shear rate calculations. The cell
      free layer containing the glycocalyx was also visualized. Comparison of the
      current microscopic resolution with theoretical, diffraction limited resolution
      let us conclude that an about sixty-fold THG signal intensity increase may be
      possible with future improved optics, optimized for 1200-1300 nm excitation. THG
      microscopy is compatible with simultaneous two-photon excited fluorescence
      detection. It thus also provides the opportunity to determine important
      hemodynamic parameters in parallel to common fluorescent observations without
      additional label. 

PMID- 24933028
TI  - In vitro and in vivo release characteristics of Tacrolimus (FK506) from an
      episcleral drug-delivery implant.
AB  - PURPOSE: To investigate the in vitro and in vivo release characteristics of
      Tacrolimus (FK506) from an episcleral drug-delivery implant. METHODS: For in
      vitro experiments, Tacrolimus-loaded implants (0.5 mL; at concentrations of 0.25,
      0.5, and 1.0 mg/mL) were immersed in a balanced salt solution. Samples of the
      surrounding liquid were aspirated at different times over a 96-h period. For in
      vivo experiments, the experimental group received an implant loaded with
      Tacrolimus (0.5 mg/mL; 0.5 mL); the control group was given a subconjunctival
      injection of 0.5 mL Tacrolimus (0.5 mg/mL). On postoperative days 3, 7, 14, 28,
      and 56, 3 animals were sacrificed, and their eyes were enucleated. Tacrolimus
      concentrations were determined by liquid chromatographic-tandem mass
      spectrometry. Ocular toxicity was evaluated by slit-lamp photography, fundus
      photography, intraocular pressure (IOP), and histology. RESULTS: The implants
      released Tacrolimus in a biphasic pattern for 96 h in the in vitro study. The
      release kinetics were not dependent on the drug concentrations. The in vivo study
      showed statistically significant differences between the 2 treatment groups.
      Tacrolimus levels were particularly high in the conjunctiva, iris, ciliary body,
      cornea, sclera, choroid, and retina in the experimental group, while
      concentrations were low and only lasted for 1 week in the controls. Slit-lamp
      photography, fundus photography, IOP, and histology showed no evidence of toxic
      effects. CONCLUSIONS: The episcleral drug-delivery implant mechanically released
      Tacrolimus through the apertures of capsules and, consequently, may be a
      promising drug vehicle for the treatment of immune-mediated ocular disorders.

PMID- 24933030
TI  - Efficient utilization of greenhouse gases in a gas-to-liquids process combined
      with CO2/steam-mixed reforming and Fe-based Fischer-Tropsch synthesis.
AB  - Two process models for carbon dioxide utilized gas-to-liquids (GTL) process
      (CUGP) mainly producing light olefins and Fischer-Tropsch (F-T) synthetic oils
      were developed by Aspen Plus software. Both models are mainly composed of a
      reforming unit, an F-T synthesis unit and a recycle unit, while the main
      difference is the feeding point of fresh CO2. In the reforming unit, CO2
      reforming and steam reforming of methane are combined together to produce syngas
      in flexible composition. Meanwhile, CO2 hydrogenation is conducted via reverse
      water gas shift on the Fe-based catalysts in the F-T synthesis unit to produce
      hydrocarbons. After F-T synthesis, the unreacted syngas is recycled to F-T
      synthesis and reforming units to enhance process efficiency. From the simulation
      results, it was found that the carbon efficiencies of both CUGP options were
      successfully improved, and total CO2 emissions were significantly reduced,
      compared with the conventional GTL processes. The process efficiency was
      sensitive to recycle ratio and more recycle seemed to be beneficial for improving
      process efficiency and reducing CO2 emission. However, the process efficiency was
      rather insensitive to split ratio (recycle to reforming unit/total recycle), and
      the optimum split ratio was determined to be zero. 

PMID- 24933029
TI  - Subthalamic nucleus deep brain stimulation induces motor network BOLD activation:
      use of a high precision MRI guided stereotactic system for nonhuman primates.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) is a powerful method for
      identifying in vivo network activation evoked by deep brain stimulation (DBS).
      OBJECTIVE: Identify the global neural circuitry effect of subthalamic nucleus
      (STN) DBS in nonhuman primates (NHP). METHOD: An in-house developed MR image
      guided stereotactic targeting system delivered a mini-DBS stimulating electrode,
      and blood oxygenation level-dependent (BOLD) activation during STN DBS in healthy
      NHP was measured by combining fMRI with a normalized functional activation map
      and general linear modeling. RESULTS: STN DBS significantly increased BOLD
      activation in the sensorimotor cortex, supplementary motor area, caudate nucleus,
      pedunculopontine nucleus, cingulate, insular cortex, and cerebellum (FDR <
      0.001). CONCLUSION: Our results demonstrate that STN DBS evokes neural network
      grouping within the motor network and the basal ganglia. Taken together, these
      data highlight the importance and specificity of neural circuitry activation
      patterns and functional connectivity.

PMID- 24933031
TI  - Accumulation of oxidative stress-related gene polymorphisms and the risk of
      coronary heart disease events in patients with type 2 diabetes--an 8-year
      prospective study.
AB  - OBJECTIVE: Oxidative stress, which is provoked in patients with diabetes, plays
      critical roles in the pathogenesis of coronary heart disease (CHD). We
      simultaneously determined 5 relatively common genetic variants related to
      oxidative stress and evaluated the combined effect on CHD. METHODS: We enrolled
      1977 Japanese type 2 diabetic subjects without history of CVD (males 66.1%, 59.5
      +/- 10.0 years old), determined their genotypes regarding glutamate-cysteine
      ligase modifier subunit (GCLM) C-588T, manganese superoxide dismutase (SOD2)
      Val16Ala, endothelial nitric oxide synthase (NOS3) G894T, NAD(P)H oxidase p22phox
      (CYBA) C242T, and myeloperoxidase (MPO) G-463A polymorphisms, and prospectively
      evaluated the association between these polymorphisms and CHD events. RESULTS:
      The median follow-up period was 7.5 years and there were 85 new CHD events. The
      single association analysis revealed that there were no statistically significant
      associations between each polymorphism and the prevalence of CHD. Interestingly,
      the risk of CHD event was higher with the increase of the total number of 10
      concomitant unfavorable "pro-oxidant alleles" in each subject (p for trend =
      0.018, log-rank test). Especially, the carriers of >=8 pro-oxidant alleles had a
      significantly increased risk as compared to the carriers of <8 pro-oxidant
      alleles, whether the other clinical variables were adjusted (HR 2.92 with 95%CI
      1.50-5.67, p = 0.002) or not (HR 2.89 with 95%CI 1.49-5.59, p = 0.002)..
      CONCLUSIONS: Accumulation of gene polymorphisms related to oxidative stress is
      likely associated with the development of CHD in patients with type 2 diabetes,
      suggesting that the combined information about these variants is useful to assess
      the risk of CHD.

PMID- 24933032
TI  - Insulin-induced glucose control improves HDL cholesterol levels but not reverse
      cholesterol transport in type 2 diabetic patients.
AB  - Type 2 diabetes (T2D) is characterized by low HDL cholesterol (HDL-C) and HDL
      dysfunction. We herein tested whether lowering HbA1c affects HDL-C and reverse
      cholesterol transport (RCT). Forty-two uncontrolled T2D patients initiating basal
      insulin were included. HbA1c, HDL-C and RCT were assessed at baseline and after 6
      months. At baseline, HDL-C and RCT were directly correlated (r = 0.50; p <
      0.001). After 6 months of insulin therapy, HbA1c dropped from 8.8 +/- 0.16% to
      7.1 +/- 0.1%, while average HDL-C and RCT did not change. Follow-up HDL-C and RCT
      were still correlated (r = 0.31; p = 0.033) and DeltaHDL-C correlated with
      DeltaRCT (r = 0.32; p = 0.029). DeltaHbA1c correlated with DeltaHDL-C (r = 0.43,
      p = 0.001), but not with DeltaRCT. In patients with DeltaHbA1c above the median
      value (1.3%), HDL-C (but not RCT) increased significantly. In conclusion, glucose
      control correlates with increased HDL-C, but not with improved RCT. Thus,
      persistent HDL dysfunction despite improved HbA1c and HDL-C can contribute to
      residual cardiovascular risk in T2D. 

PMID- 24933033
TI  - Optimal part and module selection for synthetic gene circuit design automation.
AB  - An integral challenge in synthetic circuit design is the selection of optimal
      parts to populate a given circuit topology, so that the resulting circuit
      behavior best approximates the desired one. In some cases, it is also possible to
      reuse multipart constructs or modules that have been already built and
      experimentally characterized. Efficient part and module selection algorithms are
      essential to systematically search the solution space, and their significance
      will only increase in the following years due to the projected explosion in part
      libraries and circuit complexity. Here, we address this problem by introducing a
      structured abstraction methodology and a dynamic programming-based algorithm that
      guaranties optimal part selection. In addition, we provide three extensions that
      are based on symmetry check, information look-ahead and branch-and-bound
      techniques, to reduce the running time and space requirements. We have evaluated
      the proposed methodology with a benchmark of 11 circuits, a database of 73 parts
      and 304 experimentally constructed modules with encouraging results. This work
      represents a fundamental departure from traditional heuristic-based methods for
      part and module selection and is a step toward maximizing efficiency in synthetic
      circuit design and construction. 

PMID- 24933035
TI  - The mourning after: the potential for critical care nurses to improve family
      outcome and experience in end of life care.

PMID- 24933036
TI  - Clinical utility of immunohistochemistry and other ancillary techniques in
      assessment of uterine tumors.

PMID- 24933034
TI  - Therapeutic targeting of autophagy in cancer. Part II: pharmacological modulation
      of treatment-induced autophagy.
AB  - Autophagy, the catabolic pathway in which cells recycle organelles and other
      parts of their own cytoplasm, is increasingly recognised as an important
      cytoprotective mechanism in cancer cells. Several cancer treatments stimulate the
      autophagic process and when autophagy is inhibited, cancer cells show an enhanced
      response to multiple treatments. These findings have nourished the theory that
      autophagy provides cancer cells with a survival advantage during stressful
      conditions, including exposure to therapeutics. Therefore, interference with the
      autophagic response can potentially enhance the efficacy of cancer therapy. In
      this review we examine two approaches to modulate autophagy as complementary
      cancer treatment: inhibition and induction. Inhibition of autophagy during cancer
      treatment eliminates its cytoprotective effects. Conversely, induction of
      autophagy combined with conventional cancer therapy exerts severe cytoplasmic
      degradation that can ultimately lead to cell death. We will discuss how autophagy
      can be therapeutically manipulated in cancer cells and how interactions between
      the conventional cancer therapies and autophagy modulation influence treatment
      outcome. 

PMID- 24933038
TI  - Evidenced based review of recommendations addressing the frequency of changing
      long-term indwelling urinary catheters in older adults.
AB  - The frequency of changing long-term indwelling urinary catheters is a subject of
      debate. The focus of this integrative review is to determine if routinely
      scheduled changes of long-term indwelling urinary catheters in older adults is
      evidence-based. There are no current research studies specifically studying
      routine changes of chronic indwelling urinary catheters available to support or
      refute this common practice. The frequency of chronic urinary catheter changes
      should be tailored to the individual patient and occur as clinically indicated.
      Rigorous research studies are needed to advance the science used to provide
      evidence-based care for this vulnerable population. 

PMID- 24933037
TI  - Determination of trace acrylamide in starchy foodstuffs by HPLC using a novel
      mixed-mode functionalized calixarene sorbent for solid-phase extraction cleanup.
AB  - In this paper, a rapid and effective HPLC method, using
      tetraazacalix[2]arene[2]triazine-modified silica gel (NCSi) as solid-phase
      extraction (SPE) sorbent, was developed for the purification and determination of
      trace acrylamide in starchy foodstuffs. The main influence factors of SPE
      including amount of NCSi sorbent, sample flow rate, and volume and composition of
      washing solution were investigated and evaluated in the sample pretreatment step.
      The optimized purification effect was achieved at the sample flow rate of 3
      mL/min with 100 mg of NCSi and 2 mL of washing solution (water, 100%). The HPLC
      separation was carried out on a C18 column (250*4.6 mm i.d., 5 MUm) with a mobile
      phase of methanol/water (10:90, v/v). The linear range of the calibration curve
      was 4-4000 ng/mL with s correlation coefficient of >0.9999. The intraday and
      interday RSDs (n=5) of peak areas of acrylamide were 0.22 and 0.90% and the
      intraday and interday RSDs (n=5) of retention times were 0.50 and 1.63%,
      respectively. In addition, overall recoveries through the extraction and NCSi-SPE
      purification ranged from 73.13 to 98%. Compared with the commercial SPE sorbents,
      NCSi featured excellent selectivity to retain polar and nonpolar interferences in
      the sample matrices. The improved method was simple, rapid, accurate, and
      promising for the determination of trace acrylamide in starchy foods with a
      complex matrix.

PMID- 24933039
TI  - Seroepidemiology of Toxoplasma gondii infection in Bai and Han ethnic groups in
      southwestern China.
AB  - Eating raw pork and/or liver is a custom of the Bai ethnic group in China. Most
      people living in Dali Bai Autonomous Prefecture, Yunnan Province, southwestern
      China are of Bai ethnicity. Little is known of the seroprevalence of Toxoplasma
      gondii in Bai and Han ethnic populations in this region. In the present survey, a
      total of 555 and 595 blood samples were obtained from Bai and Han ethnic groups
      in Dali urban and rural areas, respectively. Enzyme-linked immunosorbent assay
      was performed to examine T. gondii IgG antibodies. Total positive rate of anti-T.
      gondii IgG in Bai and Han groups in this region was 21.6% (248/1150). The total
      seroprevalence of T. gondii was significantly higher in the Bai ethnic group
      (32.3%, 179/555) than in the Han ethnic group (11.6%, 69/595) (P < 0.01). The
      results of statistical analysis indicated that there was no significant
      difference between cat feeding/non-cat feeding groups in the Bai ethnic group,
      the most important risk factor was consumption of raw pork and/or liver for the
      Bai group, but feeding a cat may be the main route of T. gondii infection for the
      Han group. Therefore, it is essential to implement integrated strategies to
      prevent and control T. gondii infection in this unique region of the world.

PMID- 24933040
TI  - The role of social support in dialysis patients' feelings of autonomy and self
      esteem: is support more beneficial for patients with specific illness
      perceptions?
AB  - The purpose of this study was to investigate whether effects of various types of
      support on dialysis patients' perceived autonomy and self-esteem depend on
      patients' perceived concerns and personal control regarding their illness. One
      hundred sixty-six patients completed written questionnaires. Main and interaction
      effects of support, concern, and personal control on autonomy and self-esteem
      were examined using linear regression analyses. General emotional support was
      positively related to autonomy in highly concerned patients (p < .05).
      Overprotection was negatively associated with autonomy (p < .05), and this
      association was stronger in patients with high perceived personal control (p <
      .01). A positive main effect of general emotional support (p < .05) and a
      negative main effect of overprotection (p < .01) on self-esteem were observed.
      The role of support in dialysis patients' autonomy appears to depend on patients'
      illness perceptions, whereas the role of support in patients' self-esteem does
      not. These findings suggest that dialysis patients' personal views about their
      illness can provide insight into whether patients could benefit from support, and
      that the provision of support should be tailored to patients' individual needs.

PMID- 24933041
TI  - The beta-adrenergic system as a possible new target for pharmacologic treatment
      of neovascular retinal diseases.
AB  - Retinal neovascular pathologies, such as diabetic retinopathy, retinopathy of
      prematurity (ROP) and age-related macular degeneration, may be treated with
      intravitreal injections of drugs targeting vascular endothelial growth factor
      (VEGF), the main inducer of neoangiogenesis; however further improvements and
      alternative strategies are needed. In the last few years, an intense research
      activity has focused on the beta-adrenergic system. The results indicate that, in
      different experimental models, a decrease of the beta-adrenergic function may
      result either in reduction or in exacerbation of the vascular changes, thus
      suggesting possible dual effects of beta-adrenoreceptor (beta-AR) modulation
      depending on the experimental setting. In in vivo models of proliferative
      retinopathies, most of the data point to a strong inhibitory role against
      vascular changes exerted by the blockade of specific beta-ARs. In particular, the
      beta2-AR seems to be the mostly involved in these responses, and the beta1-/beta2
      AR blocker propranolol results highly effective in inhibiting both the increase
      of VEGF expression caused by a hypoxic insult and the consequent neovascular
      response. These observations have prompted clinical trials in preterm infants
      with ROP, where oral administrations of propranolol produced positive results in
      terms of efficacy, although safety problems were also reported. In addition, the
      possibility of using topical propranolol administrations in the form of eye drops
      opens new potential routes of drug administration in humans. A further point that
      should be considered is that there are data demonstrating significant
      antiapoptotic effects exerted by beta-ARs, therefore if beta-AR blockers were
      used to inhibit aberrant neovascularization, there may be a burden to pay in
      terms of impaired neuronal viability. 

PMID- 24933043
TI  - Role of sterically demanding chiral dirhodium catalysts in site-selective C-H
      functionalization of activated primary C-H bonds.
AB  - The influence of sterically demanding dirhodium tetracarboxylate catalysts on the
      site selectivity of C-H functionalization by means of rhodium carbene-induced C-H
      insertion is described. The established dirhodium tetraprolinate-catalyzed
      reactions of aryldiazoacetates cause preferential C-H functionalization of
      secondary C-H bonds as a result of competing steric and electronic effects. The
      sterically more demanding dirhodium tetrakis(triarylcyclopropanecarboxylate)
      catalysts, exemplified by dirhodium tetrakis[(R)-(1-(biphenyl)-2,2
      diphenylcyclopropanecarboxylate)] [Rh2(R-BPCP)4], favor C-H functionalization of
      activated primary C-H bonds. Highly site-selective and enantioselective C-H
      functionalization of a variety of simple substrates containing primary benzylic,
      allylic, and methoxy C-H bonds was achieved with this catalyst. The utility of
      this approach has been demonstrated by the late-stage primary C-H
      functionalization of (-)-alpha-cedrene and a steroid. 

PMID- 24933042
TI  - Stem cells as source for retinal pigment epithelium transplantation.
AB  - Inherited maculopathies, age related macular degeneration and some forms of
      retinitis pigmentosa are associated with impaired function or loss of the retinal
      pigment epithelium (RPE). Among potential treatments, transplantation approaches
      are particularly promising. The arrangement of RPE cells in a well-defined tissue
      layer makes the RPE amenable to cell or tissue sheet transplantation. Different
      cell sources have been suggested for RPE transplantation but the development of a
      clinical protocol faces several obstacles. The source should provide a sufficient
      number of cells to at least recover the macula area. Secondly, cells should be
      plastic enough to be able to integrate in the host tissue. Tissue sheets should
      be considered as well, but the substrate on which RPE cells are cultured needs to
      be carefully evaluated. Immunogenicity can also be an obstacle for effective
      transplantation as well as tumorigenicity of not fully differentiated cells.
      Finally, ethical concerns may represent drawbacks when embryo-derived cells are
      proposed for RPE transplantation. Here we discuss different cell sources that
      became available in recent years and their different properties. We also present
      data on a new source of human RPE. We provide a protocol for RPE differentiation
      of retinal stem cells derived from adult ciliary bodies of post-mortem donors. We
      show molecular characterization of the in vitro differentiated RPE tissue and
      demonstrate its functionality based on a phagocytosis assay. This new source may
      provide tissue for allogenic transplantation based on best matches through
      histocompatibility testing. 

PMID- 24933044
TI  - Glutathione-facilitated design and fabrication of gold nanoparticle-based logic
      gates and keypad lock.
AB  - In this paper, we describe how we developed a simple design and fabrication
      method for logic gates and a device by using a commercially available tripeptide,
      namely glutathione (GSH), together with metal ions and disodium
      ethylenediaminetetraacetate (EDTA) to control the dispersion and aggregation of
      gold nanoparticles (NPs). With the fast adsorption of GSH on gold NPs and the
      strong coordination of GSH with metal ions, the addition of GSH and Pb(2+) ions
      immediately resulted in the aggregation of gold NPs, giving rise to an AND
      function. Either Pb(2+) or Ba(2+) ions induced the aggregation of gold NPs in the
      presence of GSH, supporting an OR gate. Based on the fact that EDTA has a strong
      capacity to bind metal ions, thus preventing the aggregation of gold NPs, an
      INHIBIT gate was also fabricated. More interestingly, we found that the addition
      sequence of GSH and Hg(2+) ions influenced the aggregation of gold NPs in a
      controlled manner, which was used to design a sequential logic gate and a three
      input keypad lock for potential use in information security. The GSH strategy
      addresses concerns of low cost, simple fabrication, versatile design and easy
      operation, and offers a promising platform for the development of functional
      logic systems. 

PMID- 24933045
TI  - What is the best fluid for volume resuscitation in critically ill adults with
      sepsis? The jury is still out, but a verdict is urgently needed ...*.

PMID- 24933046
TI  - On the lack of standardized essential PICU guidelines*.

PMID- 24933047
TI  - Identifying the ICU recidivist in the hospital*.

PMID- 24933048
TI  - The ongoing challenge of evaluating rescue therapies in acute respiratory
      distress syndrome*.

PMID- 24933049
TI  - Adipose tissue on CT scans in critical care and trauma are associated with acute
      kidney injury*.

PMID- 24933050
TI  - Sickle cell patients face death in the ICU*.

PMID- 24933051
TI  - Antibiotic dosing during renal replacement therapy: one size does not fit all*.

PMID- 24933052
TI  - Timing of corticosteroids in refractory septic shock: a key or wishful
      thinking?*.

PMID- 24933054
TI  - Survival for the cirrhotic patient with septic shock*.

PMID- 24933053
TI  - Exploring the boundaries of systemic inflammation*.

PMID- 24933055
TI  - Blood transfusions and infected lungs--worse outcomes?*.

PMID- 24933056
TI  - Never waste an opportunity to debrief*.

PMID- 24933057
TI  - Chlorhexidine-impregnated dressing: an efficient weapon against catheter-related
      bloodstream infection?*.

PMID- 24933058
TI  - Paving a new road for generating evidence-based care in sepsis*.

PMID- 24933059
TI  - Regional lung strain and the metabolic signature of injury*.

PMID- 24933060
TI  - Selepressin in septic shock: sharpening the VASST effects of vasopressin?*.

PMID- 24933061
TI  - Muscle-specific inhibition of the classical nuclear factor-kappaB pathway is
      protective against diaphragmatic weakness in murine endotoxemia.
AB  - OBJECTIVE: Diaphragmatic weakness and acute respiratory failure are common in
      sepsis. Nuclear factor-kappaB acts as a general coordinator of the systemic
      inflammatory response, but its role within the diaphragm itself during sepsis is
      unknown. We investigated the potential protective effect upon the diaphragm of
      inhibiting nuclear factor-kappaB only within muscle fibers during acute
      endotoxemia. DESIGN: Prospective study in experimental animals. SETTING:
      University research laboratory. INTERVENTIONS: Wild-type and transgenic (muscle
      specific IkappaBalpha super-repressor) mice with skeletal muscle-specific
      inhibition of the classical nuclear factor-kappaB pathway were subjected to acute
      endotoxemia. Muscle-specific ubiquitin ligases (muscle RING-finger protein 1 and
      atrogin-1), caspase-3 activity, inhibitor of apoptosis proteins, proinflammatory
      cytokines (interleukin-1beta, monocyte chemoattractant protein-1, and tumor
      necrosis factor-alpha), and diaphragmatic contractility were evaluated after 24
      hours. MEASUREMENTS AND MAIN RESULTS: In wild-type mice, endotoxemia
      significantly increased proinflammatory cytokines (fold-change messenger RNA:
      interleukin-1beta = 7.6, monocyte chemoattractant protein-1 = 15.3, and tumor
      necrosis factor-alpha = 2.2) and proteolysis effectors (fold-change messenger
      RNA: muscle RING-finger protein 1 = 5.7, atrogin-1 = 2.8; caspase-3 activity
      elevated by 28%) in the diaphragm, while reducing its force-generating capacity
      by 38%. In nonendotoxemic muscle-specific IkappaBalpha super-repressor
      diaphragms, caspase-3 activity was unexpectedly increased by 40% above basal wild
      type levels and inhibitors of apoptosis proteins were down-regulated, but force
      production remained normal. In muscle-specific IkappaBalpha super-repressor mice
      subjected to endotoxemia, proinflammatory cytokines, muscle RING-finger protein
      1, and atrogin-1 were not significantly increased above their basal levels, and
      diaphragmatic weakness and further increases in caspase-3 activity were
      completely prevented. CONCLUSIONS: These results suggest that nuclear factor
      kappaB signaling within skeletal muscle fibers is a key pathway leading to
      diaphragmatic weakness during acute endotoxemia, most likely via effects on
      multiple inflammatory mediators. In addition, inhibition of nuclear factor-kappaB
      signaling within diaphragm muscle fibers has complex effects on caspase-3
      activation, which could have implications for the treatment of sepsis-induced
      diaphragmatic dysfunction.

PMID- 24933062
TI  - End-of-life care and deactivation of left ventricular assist devices.

PMID- 24933063
TI  - The authors reply.

PMID- 24933064
TI  - Time to break down silos: alternative approaches to staffing ICUs.

PMID- 24933065
TI  - The authors reply.

PMID- 24933066
TI  - Comments on perioperative fluid therapy with tetrastarch and gelatin in cardiac
      surgery--a prospective sequential analysis.

PMID- 24933067
TI  - The authors reply.

PMID- 24933068
TI  - The role of fibroblast growth factor 23 in sepsis.

PMID- 24933069
TI  - The authors reply.

PMID- 24933070
TI  - Choice of renal replacement therapy modality and long-term dialysis dependence.
      Where do we stand after three decades?

PMID- 24933071
TI  - The author replies.

PMID- 24933072
TI  - Simulation and its role in airway management training.

PMID- 24933073
TI  - The authors reply.

PMID- 24933074
TI  - External ventricular drain-related ventriculitis prevention: standard preventive
      measures still work.

PMID- 24933075
TI  - The authors reply.

PMID- 24933076
TI  - Can global end-diastolic volume index influence the occurrence of delayed
      cerebral ischemia and pulmonary edema after subarachnoid hemorrhage?

PMID- 24933077
TI  - Use of therapeutic hypothermia after in-hospital cardiac arrest: did the
      physicians know the guidelines?

PMID- 24933078
TI  - The authors reply.

PMID- 24933079
TI  - Imogolite: an aluminosilicate nanotube endowed with low cytotoxicity and
      genotoxicity.
AB  - High-aspect-ratio nanomaterials (HARN) (typically, single-walled carbon nanotubes
      (SWCNT) or multiwalled carbon nanotubes (MWCNT)) impair airway barrier function
      and are toxic to macrophages. Here, we assess the biological effects of nanotubes
      of imogolite (INT), a hydrated alumino-silicate [(OH)3Al2O3SiOH] occurring as
      single-walled NT, on murine macrophages and human airway epithelial cells. Cell
      viability was assessed with resazurin. RT-PCR was used to study the expression of
      Nos2 and Arg1, markers of classical or alternative macrophage activation,
      respectively, and nitrite concentration in the medium was determined to assess NO
      production. Epithelial barrier integrity was evaluated from the trans-epithelial
      electrical resistance (TEER). Potential genotoxicity of INT was assessed with
      comet and cytokinesis-block micronucleus cytome assays. Compared to MWCNT and
      SWCNT, INT caused much smaller effects on RAW264.7 and MH-S macrophage viability.
      The incubation of macrophages with INT at doses as high as 120 MUg/cm(2) for 72 h
      did not alter either Nos2 or Arg1 expression nor did it increase NO production,
      whereas IL6 was induced in RAW264.7 cells but not in MH-S cells. INT did not show
      any genotoxic effect in RAW264.7 and A549 cells except for a decrease in DNA
      integrity observed in epithelial A549 cells after treatment with the highest dose
      (80 MUg/cm(2)). No significant change in permeability was recorded in Calu-3
      epithelial cell monolayers exposed to INT, whereas comparable doses of both SWCNT
      and MWCNT lowered TEER. Thus, in spite of their fibrous nature, INT appear not to
      be markedly toxic for in vitro models of lung-blood barrier cells. 

PMID- 24933080
TI  - Plasma adiponectin levels and relations with cytokines in children with acute
      rheumatic fever.
AB  - AIM: We aimed to investigate the role of adiponectin in acute rheumatic fever by
      evaluating correlations with cytokines and acute-phase reactants. METHODS:
      Patients were divided into three groups by clinical findings. Group 1 included 8
      patients with only chorea, Group 2 included 13 patients with arthritis and
      carditis, and Group 3 included 12 patients with only carditis. A total of 54 age-
      and gender-matched children were enrolled in the control group. Blood samples
      were drawn for analysing acute-phase reactants, adiponectin, tumour necrosis
      factor-alpha, interleukin-6, and interleukin-8 levels at baseline on Days 2, 5,
      10, and 15, and at 8 weeks. RESULTS: There was no statistically significant
      difference between baseline age, gender, body mass index, serum triglyceride,
      total cholesterol, and low-density lipoprotein levels of the study and control
      groups (p>0.05). No correlation was found between baseline plasma adiponectin
      levels, age, body mass index, follicle-stimulating hormone, luteinising hormone,
      oestradiol, total testosterone, and blood lipid levels of the study and control
      groups (p>0.05). We found that adiponectin and interleukin-6 levels increased,
      tumour necrosis factor-alpha levels decreased, and interleukin-8 levels remained
      unchanged in acute rheumatic fever, which is an inflammatory disease. Moreover,
      adiponectin level was higher and tumour necrosis factor-alpha level was lower in
      the improvement period in comparison with the acute period, particularly in the
      carditis group. CONCLUSION: It was considered that, increasing throughout the
      treatment period, adiponectin may have anti-inflammatory effects in acute
      rheumatic fever. In addition, adiponectin levels are associated with a decline in
      inflammatory mediators in rheumatic fever.

PMID- 24933082
TI  - Wilms' tumor--lessons and outcomes--a 25-year single center UK experience.
AB  - Wilms' tumor (WT) is a common childhood renal cancer. A 25-year single center UK
      experience is reported. During 1985-2010, 97 children underwent immediate
      nephrectomy or delayed resection of tumor after chemotherapy. Survival,
      morbidity, and late effects following treatment are described. Tumor distribution
      was: Stage I, 25.7% (n = 25); Stage II, 24.7% (n = 24); Stage III, 26.8% (n =
      26); Stage IV, 17.5% (n = 17); and Stage V, 5.2% (n = 5). Immediate nephrectomy
      was performed in 39% (n = 38) patients with elective delayed resection in 61% (n
      = 59) cases. Ten patients had cavotomy to excise tumor involving vena cava
      territory. Two cases required cardiopulmonary bypass. Tumor rupture was recorded
      in eight (8.5%) total operated cases-after immediate (n = 5/37), 13.5% vs delayed
      nephrectomy-(n = 3/57), 5.2%; X(2) P = .154. From 2001 onwards, one case of tumor
      rupture was recorded at this center after the universal adoption of UKW3 and SIOP
      guidelines advocating preoperative chemotherapy and delayed nephrectomy for all
      WT. Three treatment-related deaths occurred-hepatic veno-occlusive disease (n =
      2) with actinomycin D and a single WT fatality due to vascular injury. Overall
      survival was 84.5% (82/97 cases). Two patients developed "late malignancies" 
      thyroid cancer and a basal cell carcinoma. This study demonstrates excellent
      survival for WT comparable with national outcomes and international cooperative
      studies. Adverse events with chemotherapy and surgery, including "late onset,"
      second malignancies deserve special consideration.

PMID- 24933081
TI  - Efficacy assessment of an MVA vectored Rift Valley Fever vaccine in lambs.
AB  - The present study has evaluated the protection conferred by a single subcutaneous
      dose of a modified vaccinia virus Ankara (MVA) vectored vaccine encoding the Rift
      Valley Fever virus (RVFV) glycoproteins Gn and Gc in lambs. Three groups of six
      to seven lambs were immunized as follows: one group received the vaccine (termed
      rMVA-GnGc), a second group received an MVA vector (vector control) and a third
      group received saline solution (non-vaccinated control). Fourteen days later, all
      animals were subcutaneously challenged with 10(5) TCID50 of the virulent RVFV
      isolate 56/74 and vaccine efficacy assessed using standard endpoints. Two lambs
      (one from the vaccine group and one from the vector control group) succumbed to
      RVFV challenge, showing characteristic liver lesions. Lambs from both the vector
      control and non-vaccinated groups were febrile from days 2 to 5 post challenge
      (pc) while those in the rMVA-GnGc group showed a single peak of pyrexia at day 3
      pc. RVFV RNA was detected in both nasal and oral swabs from days 3 to 7 pc in
      some lambs from the vector control and non-vaccinated groups, but no viral
      shedding could be detected in the surviving lambs vaccinated with rMVA-GnGc.
      Together, the data suggest that a single dose of the rMVA-GnGc vaccine may be
      sufficient to reduce RVFV shedding and duration of viremia but does not provide
      sterile immunity nor protection from disease. Further optimization of this
      vaccine approach in lambs is warranted. 

PMID- 24933083
TI  - Does nighttime exercise really disturb sleep? Results from the 2013   National
      Sleep Foundation Sleep in America Poll.
AB  - OBJECTIVE: To assess the relationship between sleep, time of exercise, and
      intensity of exercise in a large American sample. METHODS: The 2013 National
      Sleep Foundation Sleep in America Poll was a cross-sectional study of 1000 adults
      stratified by age (23-60 years) and U.S. geographical region. Sleep outcomes
      included self-reported sleep quality, total sleep time, sleep latency, and waking
      unrefreshed. Exercise timing was characterized as morning (>8 h before bed),
      afternoon (4-8 h before bed), or evening (<4 h before bed). Exercise intensity
      was assessed with a modified version of the International Physical Activity
      Questionnaire. RESULTS: After adjustment for confounders, evening moderate or
      vigorous exercisers did not differ in any of the reported sleep metrics compared
      to non-exercisers. Morning vigorous exercisers had the most favorable sleep
      outcomes, including greater likelihood of reporting good sleep quality (OR =
      1.88, p < .001) and lower likelihood of waking unrefreshed (OR = 0.56, p = .03).
      Most individuals who performed vigorous evening exercise believed that their
      sleep was of equal or better quality (97%) and duration (98%) on days they
      exercised. CONCLUSION: Evening exercise was not associated with worse sleep.
      These findings add to the growing body of evidence that sleep hygiene
      recommendations should not discourage evening exercise.

PMID- 24933084
TI  - Sleep timing, chronotype, mood, and behavior at an Arctic latitude (69 degrees 
      N).
AB  - OBJECTIVE: Daylight is an important zeitgeber for entraining the circadian rhythm
      to a 24 h clock cycle, especially within the Polar circle, which has long Polar
      nights several months each year. Phase delays in sleep timing may occur, but the
      mean shift is normally small. However, the individual variation in phase shifts
      is large, implicating moderating factors. Here we examined the role of several
      self-regulatory variables (mood and fatigue, behavioral habits, and psychological
      self-regulation) as moderators of seasonality in sleep timing and chronotype.
      METHODS: A sample of 162 young adults (76% females; mean age: females 23.4 years,
      males 24.3 years) participated in a prospective study across three seasons
      (September, December, March) in Tromso/Norway at 69 degrees 39'N Sleep diary and
      sleep/health-related questionnaire data were collected at each time-point.
      RESULTS: Sleep timing and chronotype were delayed during the dark period
      (December) compared with brighter photoperiods (September and March). Comparable
      effects were observed for insomnia, fatigue, mood (depression and anxiety),
      subjective health complaints, physical activity, and school-related stress. Most
      importantly, depression and fatigue moderated the degree of seasonal shifting in
      sleep timing, whereas the other self-regulation indicators did not (ie eating
      habits, physical activity, and psychological self-regulation). CONCLUSION:
      Seasonality in sleep timing and chronotype was confirmed, and it seems that
      depressive symptoms during the dark period exacerbate phase-shifting problems for
      people living in sub-Arctic regions.

PMID- 24933085
TI  - Response to, ''The unnormalized spectral indices of heart rate variability should
      be presented in conjunction with normalized versions of the same variables''.

PMID- 24933086
TI  - In brief: a naloxone auto-injector (Evzio).

PMID- 24933087
TI  - Extended-release hydrocodone (Zohydro) for pain.

PMID- 24933088
TI  - Sublingual immunotherapy for allergic rhinitis.

PMID- 24933089
TI  - In brief: lowering the dose of Lunesta.

PMID- 24933090
TI  - Redox-responsive nanocarrier based on heparin end-capped mesoporous silica
      nanoparticles for targeted tumor therapy in vitro and in vivo.
AB  - This study reports a smart controlled drug release system based on mesoporous
      silica nanoparticles (MSNs) for targeted drug delivery. The system was fabricated
      by employing heparin as an end-capping agent to seal the mesopores of MSNs via
      disulfide bonds as intermediate linkers for intracellular glutathione triggered
      drug release. Lactobionic acid molecules were then coupled to heparin end-capped
      MSNs that serve as targeting motifs for facilitating the uptake of doxorubicin
      (DOX) loaded MSNs by HepG2 cells and tumors, respectively. Detailed
      investigations demonstrated that the fabricated drug delivery systems could
      deliver DOX to cancer cells to induce cell apoptosis in vitro and tumor tissue
      for the inhibition of tumor growth in vivo with minimal side effects. The study
      affords a promising nanocarrier for redox-responsive cargo delivery with high
      curative efficiency for cancer therapy. 

PMID- 24933091
TI  - Dietary L-carnitine supplementation increases lipid deposition in the liver and
      muscle of yellow catfish (Pelteobagrus fulvidraco) through changes in lipid
      metabolism.
AB  - Carnitine has been reported to improve growth performance and reduce body lipid
      content in fish. Thus, we hypothesised that carnitine supplementation can improve
      growth performance and reduce lipid content in the liver and muscle of yellow
      catfish (Pelteobagrus fulvidraco), a commonly cultured freshwater fish in inland
      China, and tested this hypothesis in the present study. Diets containing l
      carnitine at three different concentrations of 47 mg/kg (control, without extra
      carnitine addition), 331 mg/kg (low carnitine) and 3495 mg/kg (high carnitine)
      diet were fed to yellow catfish for 8 weeks. The low-carnitine diet significantly
      improved weight gain (WG) and reduced the feed conversion ratio (FCR). In
      contrast, the high-carnitine diet did not affect WG and FCR. Compared with the
      control diet, the low-carnitine and high-carnitine diets increased lipid and
      carnitine contents in the liver and muscle. The increased lipid content in the
      liver could be attributed to the up-regulation of the mRNA levels of SREBP,
      PPARgamma, fatty acid synthase (FAS) and ACCa and the increased activities of
      lipogenic enzymes (such as FAS, glucose-6-phosphate dehydrogenase, 6
      phosphogluconate dehydrogenase and malic enzyme) and to the down-regulation of
      the mRNA levels of the lipolytic gene CPT1A. The increased lipid content in
      muscle could be attributed to the down-regulation of the mRNA levels of the
      lipolytic genes CPT1A and ATGL and the increased activity of lipoprotein lipase.
      In conclusion, in contrast to our hypothesis, dietary carnitine supplementation
      increased body lipid content in yellow catfish.

PMID- 24933092
TI  - Characterization of a rapid and reliable method for iodide biomonitoring in serum
      and urine based on ion chromatography-ICP-mass spectrometry.
AB  - An appropriate and controlled supply of thyroid hormones is vital for proper body
      function. In turn, an appropriate synthesis of T3 and T4 in the thyroid gland is
      dependent on a sufficient and balanced iodide concentration in blood serum. Due
      to widespread iodine deficiency or some cases of iodine over exposure, iodide
      biomonitoring in serum is important and it is that biomonitoring approach being
      closest to the bioavailable I(-) supply for the thyroid gland. Therefore, this
      paper describes a biomonitoring method for iodide determination in serum based on
      ion chromatography-inductively coupled plasma mass spectrometry (IC-ICP-MS).
      Since in literature only very few data are available on iodide in serum but many
      in urine the method is also extended to I(-) monitoring in urine. The method was
      additionally designed to have short analysis time (8min) for increased sample
      throughput, good precision in serial measurement (serum: 4.86%; urine: 1.4%), and
      day-to-day determination (serum: 5.7%; urine: 2.28%), high accuracy (serum: 105%;
      urine: 101%) and good recovery (serum: 102%; urine: 99%) even in matrix-rich
      samples at low I(-) concentration. Also, investigations were performed to
      elucidate whether internal standardization during chromatography, sample
      preparation for protein-matrix removal or matrix-matched calibration are
      advantageous for analytical performance. Finally, limits of detection (3sigma) of
      0.12MUg/L or 0.05MUg/L (serum or urine) and limit of quantification (10sigma) of
      0.39MUg/L or 0.17MUg/L (serum or urine) were achieved. 

PMID- 24933093
TI  - Taking it one day at a time: African American women aging with HIV and co
      morbidities.
AB  - Self-managing HIV/AIDS presents challenges for anyone infected. These challenges
      may be further complicated for older HIV-infected African American women who
      acquired the disease at younger ages and now have co-morbidities. Little is known
      regarding how women's age identity, social responsibilities, co-morbidities, and
      romantic relationship status influence their HIV self-management. Five focus
      groups were conducted in Washington DC, with HIV-positive African American women
      aged 52-65. Topics included HIV and co-morbidity self-management, social support
      needs, medication adherence, and future plans for old age. A constant comparison
      approach was applied during data analysis. Co-morbidities, including diabetes and
      hypertension, were perceived to be more difficult to self-manage than HIV. This
      difficulty was not attributed to aging but to daily struggles such as lack of
      income and/or health insurance, an inflexible work schedule, and loneliness.
      Social responsibilities, including caring for family, positively impacted
      participants' ability to self-manage HIV by serving as motivation to stay healthy
      in order to continue to help family members. In contrast, inflexible work
      schedules negatively impacted women's ability to sustain medication adherence.
      Overall, this study demonstrates that HIV and co-morbidity self-management are
      inextricably linked. We can no longer afford to view engagement in HIV care as a
      single-disease issue and hope to attain optimal health and well-being in our HIV
      affected populations. Optimal HIV self-management must be framed within a larger
      context that simultaneously addresses HIV and co-morbidities, while considering
      how social and cultural factors uniquely intersect to influence older African
      American women's self-management strategies.

PMID- 24933094
TI  - Relationship of sperm small heat-shock protein 10 and voltage-dependent anion
      channel 2 with semen freezability in boars.
AB  - Freezability differences between boar ejaculates exist, but there is no useful
      method to predict the ejaculate freezability before sperm cryopreservation takes
      place. In this context, the present study sought to determine whether the amounts
      of small heat-shock protein 10 (also known as outer dense fiber protein 1)
      (ODF1/HSPB10) and voltage-dependent anion channel 2 (VDAC2) may be used as boar
      sperm freezability markers. With this aim, 26 boar ejaculates were split into two
      fractions: one for protein extraction and the other for cryopreservation
      purposes. Ejaculates were subsequently classified into two groups (good
      freezability ejaculates [GFE] and poor freezability ejaculates [PFE]) based on
      viability and sperm motility assessments after 30 and 240 minutes of after
      thawing. Although the VDAC2 amounts, analyzed through Western blot, were
      significantly higher (P < 0.01) in GFE (1.15 +/- 0.18 density mm(2)) than in PFE
      (0.16 +/- 0.03 density mm(2)), no significant differences were observed in
      ODF1/HSPB10 between both groups (i.e., 1.97 +/- 0.38 density mm(2) in GFE vs.
      1.87 +/- 1.54 density mm(2) in PFE). In addition, principal component and
      multiple regression analyses indicated that the component explaining most of the
      variance (78.41%) in ejaculate freezability at 240 minutes after thawing resulted
      to be significantly (P < 0.05) correlated with VDAC2 content. This result
      revealed that the amounts of VDAC2 but not those of ODF1/HSPB10 may be used to
      predict the freezability of a given boar ejaculate before starting
      cryopreservation procedures.

PMID- 24933095
TI  - Inflammatory cytokine concentrations in uterine flush and serum samples from
      dairy cows with clinical or subclinical endometritis.
AB  - The objective of this study was to compare the concentrations of inflammatory
      cytokines in uterine flush and serum from healthy postpartum dairy cows and cows
      with clinical or subclinical endometritis. Clinical endometritis was diagnosed by
      observation of vaginal discharges (>50% pus) and subclinical endometritis was
      diagnosed by evaluation of uterine cytology (neutrophils >18%) at 4 weeks
      postpartum. Uterine flush was obtained from 48 cows at 4, 6, and 8 weeks
      postpartum for evaluation of tumor necrosis factor-alpha (TNF-alpha), interleukin
      (IL)-1beta, IL-6, IL-8, and IL-10 concentrations. Serum samples were obtained
      from 34 cows just after calving and at 1, 2, 4, 6, and 8 weeks postpartum for
      evaluation of TNF-alpha, IL-1beta, and IL-6 concentrations. Concentrations of TNF
      alpha, IL-6, and IL-10 were greater (P < 0.05) in cows with clinical endometritis
      than in cows with subclinical endometritis and healthy controls, whereas
      concentrations of IL-8 in both cows with clinical and subclinical endometritis
      were greater (P < 0.005) than in controls. Overall, IL-6 and IL-10 concentrations
      decreased during the postpartum period. IL-1beta concentrations in cows with
      clinical endometritis decreased (P < 0.0005) during the postpartum, whereas
      concentrations in cows with subclinical endometritis and controls did not change
      significantly with time; at 4 weeks postpartum, concentrations were greater (P <
      0.0001) in cows with clinical endometritis. There were no significant effects of
      group, sampling time, or interaction on serum cytokine concentrations. In
      conclusion, cows with endometritis have greater inflammatory cytokine
      concentrations in uterine flush than healthy cows, but no differences were
      observed in serum.

PMID- 24933096
TI  - Accurate early infant HIV diagnosis in primary health clinics using a point-of
      care nucleic acid test.
AB  - OBJECTIVE: To evaluate the accuracy of a point-of-care (POC) nucleic acid-based
      test (NAT) for early infant HIV diagnosis (EID) in primary health clinics in
      Mozambique. METHODS: POC and laboratory NAT EID tests were conducted on matched
      blood samples collected from 827 HIV-exposed infants younger than 18 months who
      were enrolled consecutively at 4 periurban primary health clinics and the central
      hospital in Maputo. Lancet heel draw blood collected by nurses was tested on site
      for HIV-1/-2 RNA on the Alere HIV NAT POC device and also used to create dried
      blood spots for later laboratory EID testing on the Roche Cobas Taqman/Ampliprep
      instrument. Results were used to determine the sensitivity, specificity, and
      agreement between the POC and laboratory NAT EID tests. RESULTS: The sensitivity
      and specificity of POC NAT EID testing were 98.5% (95% confidence interval (CI):
      91.7 to 99.9, n = 65) and 99.9% (95% CI: 99.3 to 100, n = 762), respectively,
      compared with laboratory EID tests. Overall agreement was high (Cohen kappa =
      0.981; 95% CI: 0.96 to 1.00). Positive (98.5%; 95% CI: 96.3 to 100) and negative
      99.9% (95% CI: 99.7 to 100) test agreement was also high. CONCLUSIONS: Primary
      health care nurses accurately performed POC NAT EID testing within primary health
      care clinics. On-site nucleic acid-based EID testing is technically feasible in
      clinic settings and could be used in efforts to improve access to pediatric HIV
      antiretroviral treatment.

PMID- 24933098
TI  - A novel straightforward synthesis of 2,4-disubstituted-1,3,5-triazines via
      aerobic copper-catalyzed cyclization of amidines with DMF.
AB  - A novel straightforward synthesis of both symmetrical and unsymmetrical 2,4
      disubstituted-1,3,5-triazines via aerobic copper-catalyzed cyclization of
      amidines with DMF as a one-carbon synthon has been developed. The presented
      method allows synthesizing the products that are currently inaccessible or
      challenging to prepare with the advantages of operational simplicity, broad
      substrate scope, and no need for prefunctionalized reagents, making it a highly
      practical approach to access various 2,4-disubstituted-1,3,5-triazines. 

PMID- 24933099
TI  - Insulin-like modulation of Akt/FoxO signaling by copper ions is independent of
      insulin receptor.
AB  - Copper ions are known to induce insulin-like effects in various cell lines,
      stimulating the phosphoinositide 3'-kinase (PI3K)/Akt signaling cascade and
      leading to the phosphorylation of downstream targets, including FoxO
      transcription factors. The aim of this work was to study the role of insulin- and
      IGF1-receptors (IR and IGF1R) in insulin-like signaling induced by copper in
      HepG2 human hepatoma cells. Cells were exposed to Cu(II) at various
      concentrations for up to 60 min. While Akt and FoxO1a/FoxO3a were strongly
      phosphorylated in copper- and insulin-treated cells at all time points studied,
      only faint tyrosine phosphorylation of IR/IGF1R was detected in cells exposed to
      Cu(II) by either immunoprecipitation/immunoblot or by immunoblotting using
      phospho-specific antibodies, whereas insulin triggered strong phosphorylation at
      these sites. Pharmacological inhibition of IR/IGF1R modestly attenuated Cu
      induced Akt and FoxO phosphorylation, whereas no attenuation of Cu-induced Akt
      activation was achieved by siRNA-mediated IR depletion. Cu(II)-induced FoxO1a
      nuclear exclusion was only slightly impaired by pharmacological inhibition of
      IR/IGF1R, whereas insulin-induced effects were blunted. In contrast, genistein, a
      broad-spectrum tyrosine kinase inhibitor, at concentrations not affecting
      IR/IGF1R, attenuated Cu(II)-induced Akt phosphorylation, pointing to the
      requirement of tyrosine kinases other than IR/IGF1R for Cu(II)-induced signaling.

PMID- 24933097
TI  - Prevalent tuberculosis at HIV diagnosis in Rio de Janeiro, Brazil: the TB/HIV in
      Rio (THRio) Cohort.
AB  - BACKGROUND: Although Brazil has model HIV care programs, many patients continue
      to present late to care. We studied the frequency of tuberculosis (TB) diagnosed
      at HIV diagnosis in Rio de Janeiro, Brazil, to quantify missed opportunities for
      TB prevention. METHODS: People living with HIV (PLHIV) and enrolled in the TB/HIV
      in Rio study between September 1, 2005, and August 31, 2009, were included.
      Prevalent TB was defined as TB diagnosed within 60 days of HIV diagnosis or HIV
      diagnosis during TB therapy. Survival was measured from HIV diagnosis. We
      conducted Kaplan-Meier survival plots and Cox regression analyses. RESULTS: Four
      thousand five hundred forty-eight newly diagnosed PLHIV were enrolled: 476
      (10.5%) with prevalent TB. Individuals with prevalent TB were older, had lower
      CD4 counts, and higher viral loads than did those without TB. Median time to
      receiving highly active antiretroviral therapy (HAART) in those with prevalent TB
      was 99 days (interquartile range = 58-191) vs. 126 days (interquartile range = 63
      301) in those without TB (P = 0.021). Among those with prevalent TB, 17% died
      during follow-up compared with 8% among those without TB (P < 0.001). After
      adjustment for sex, age, baseline CD4, and baseline viral load, the risk of
      occurrence of death remained significantly higher among those with prevalent TB
      [adjusted hazard ratio = 1.72 (confidence interval 95% 1.19 to 2.48)].
      CONCLUSIONS: More than 10% of new PLHIV in our study presented to care with
      concurrent active TB disease and thus missed the opportunity for undergoing TB
      preventive therapy. Despite initiating HAART more quickly, these individuals were
      at a significantly greater risk of death. Earlier HIV diagnosis is necessary to
      provide earlier initiation of HAART and TB preventive therapy to reduce morbidity
      and mortality in PLHIV.

PMID- 24933100
TI  - Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for
      Lynch syndrome.
AB  - OBJECTIVE: Determine factors impacting the uptake of genetic counseling and
      results of genetic testing following universal tumor testing for Lynch syndrome
      in patients with endometrial cancer. METHODS: The study population consisted of
      two unselected cohorts of endometrial cancer patients, 408 identified
      retrospectively and 206 identified prospectively. Immunohistochemistry for
      mismatch repair protein expression and/or microsatellite instability analysis was
      performed on these tumors. MLH1 methylation analysis was performed on tumors with
      loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome
      if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1
      without MLH1 promoter methylation, and/or microsatellite instability.
      Participants with suggestive tumor studies were contacted and offered genetic
      counseling and testing. RESULTS: In the retrospective cohort, 11% had tumor
      studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A
      germline mutation was detected in 40%, and one had a variant of uncertain
      significance. In the prospective cohort, 8.7% of patients had tumor testing
      suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline
      mutations were found in 40%, and one had a variant of uncertain significance.
      Common challenges included timing of re-contact, age, perceived lack of
      relevance, inability to travel and limited insurance coverage. CONCLUSIONS: There
      are several barriers to genetic counseling and testing follow-up after universal
      tumor testing, and uninformative genetic test results present a management
      challenge. It is important to consider these limitations when implementing an
      approach to screening endometrial cancer patients for Lynch syndrome.

PMID- 24933101
TI  - Postoperative readmissions following ileostomy formation among patients with a
      gynecologic malignancy.
AB  - OBJECTIVES: Ileostomy results in a relatively poorer water reabsorption and is
      associated with dehydration and renal injury. These problems may be exacerbated
      in the setting of gynecologic cancers owing to both patient and disease-related
      factors. We evaluated the rate and reasons for hospital readmission within 30
      days of ileostomy creation in patients with a gynecologic malignancy. METHODS: We
      performed a retrospective review of women with gynecologic malignancies who
      underwent ileostomy creation between 2002 and 2013. RESULTS: Fifty-three patients
      were eligible for analysis. The mean age was 63.3 years. Most patients had
      ovarian cancer (86.5%). Indications for ileostomy included small bowel
      obstruction (45.3%), as part of primary debulking (18.9%), or treatment of an
      anastomotic leak (15.1%). The 30-day readmission rate was 34%. Co-morbid diseases
      such as hypertension (p=0.008) and chronic kidney disease (p=0.010) were more
      common among women who were readmitted. The most common reasons for readmission
      were dehydration (38.9%) and acute renal failure (33.3%); women readmitted for
      these conditions had higher average serum creatinine levels at initial
      postoperative discharge (1.00 mg/dL versus 0.71 mg/dL, p=0.017) than women who
      did not require readmission. Readmitted women had a trend toward shorter overall
      survival (0.41 years versus 1.67 years, p=0.061). CONCLUSIONS: Readmission rates
      for gynecologic oncology patients undergoing ileostomy were similar to, but
      higher than those previously reported in the colorectal literature. In our
      population, patients with preexisting cardiovascular or renal disease were at the
      highest risk of readmission and may benefit from preemptive strategies to
      decrease high ostomy output and dehydration.

PMID- 24933102
TI  - Is bariatric surgery an option for women with gynecologic cancer? Examining
      weight loss counseling practices and training among gynecologic oncology
      providers.
AB  - OBJECTIVE: The objective of this study was to evaluate gynecologic oncology
      provider (GOP) practices regarding weight loss (WL) counseling, and to assess
      their willingness to initiate weight loss interventions, specifically bariatric
      surgery (WLS). METHODS: Members of the Society of Gynecologic Oncology were
      invited to complete an online survey of 49 items assessing knowledge, attitudes,
      and behaviors related to WL counseling. RESULTS: A total of 454 participants
      initiated the survey, yielding a response rate of 30%. The majority of
      respondents (85%) were practicing GOP or fellows. A majority of responders
      reported that >50% of their patient population is clinically obese (BMI >= 30).
      Only 10% reported having any formal training in WL counseling, most often in
      medical school or residency. Providers who feel adequate about WL counseling were
      more likely to offer multiple WL options to their patients (p<.05). Over 90% of
      responders believe that WLS is an effective WL option and is more effective than
      self-directed diet and medical management of obesity. Providers who were more
      comfortable with WL counseling were significantly more likely to recommend WLS
      (p<.01). Approximately 75% of respondents expressed interest in clinical trials
      evaluating WLS in obese cancer survivors. CONCLUSIONS: The present study suggests
      that GOP appreciate the importance of WL counseling, but often fail to provide
      it. Our results demonstrate the paucity of formal obesity training in oncology.
      Providers seem willing to recommend WLS as an option to their patients but also
      in clinical trials examining gynecologic cancer outcomes in women treated with
      BS.

PMID- 24933104
TI  - [What would you do with a 29-weeks pregnant woman with generalised pruritus?].
AB  - Intrahepatic cholestasis of pregnancy is a reversible disease of variable
      frequency. The pathophysiology involves an increase of the bile acids in the
      fetal blood of the mother and the fetus. The high concentrations of the bile
      acids cause maternal pruritus and high perinatal morbimortality. Primary Care
      physicians in close contact with the patient must have a high index of suspicion
      when faced with typical symptoms of cholestasis, such as generalized pruritus in
      women in the second or third trimester of gestation to be able to act on the
      consequences. 

PMID- 24933103
TI  - Associations of polymorphisms in DNA repair genes and MDR1 gene with chemotherapy
      response and survival of non-small cell lung cancer.
AB  - OBJECTIVES: We aimed to determine the associations of genetic polymorphisms of
      excision repair cross-complementation group 1 (ERCC1) rs11615, xeroderma
      pigmentosum group D (XPD/ERCC2) rs13181, X-ray repair cross complementing group 1
      (XRCC1) rs25487, XRCC3 rs1799794, and breast cancer susceptibility gene 1 (BRCA1)
      rs1799966 from the DNA repair pathway and multiple drug resistance 1 (MDR1/ABCB1)
      rs1045642 with response to chemotherapy and survival of non-small cell lung
      cancer (NSCLC) in a Chinese population. MATERIALS AND METHODS: A total of 352
      NSCLC patients were enrolled to evaluate the associations of the six SNPs with
      response to chemotherapy and overall survival. Logistic regressions were applied
      to test the associations of genetic polymorphisms with response to chemotherapy
      in 161 advanced NSCLC patients. Overall survival was analyzed in 161 advanced and
      156 early stage NSCLC patients using the Kaplan-Meier method with log-rank test,
      respectively. Multivariate Cox proportional hazards model was performed to
      determine the factors independently associated with NSCLC prognosis. RESULTS:
      BRCA1 rs1799966 minor allele C (TC+CC vs. TT, OR = 0.402, 95% CI = 0.204-0.794, p
      = 0.008) and MDR1/ABCB1 rs1045642 minor allele A (GA +AA vs. GG, OR = 0.478, 95%
      CI = 0.244-0.934, p = 0.030) were associated with a better response to
      chemotherapy in advanced NSCLC patients. Survival analyses indicated that BRCA1
      rs1799966 TC+CC genotypes were associated with a decreased risk of death (HR =
      0.617, 95% CI = 0.402-0.948, p = 0.028) in advanced NSCLC patients, and the
      association was still significant after the adjustment for covariates.
      Multivariate Cox regression analysis showed that ERCC1 rs11615 AA genotype (P =
      0.020) and smoking (p = 0.037) were associated with increased risks of death in
      early stage NSCLC patients after surgery. CONCLUSIONS: Polymorphisms of genes in
      DNA repair pathway and MDR1 could contribute to chemotherapy response and
      survival of patients with NSCLC.

PMID- 24933105
TI  - Pastoral care use among post-9/11 veterans who screen positive for mental health
      problems.
AB  - As a result of their military experience, veterans with mental health problems
      may have unique motivations for seeking help from clergy. Patterns and correlates
      of seeking pastoral care were examined using a nationwide representative survey
      that was conducted among veterans of post-9/11 conflicts (adjusted N = 1,068; 56%
      response rate). Separate multivariate logistic regression models were used to
      examine veteran characteristics associated with seeking pastoral care and seeking
      mental health services. Among post-9/11 veterans with a probable mental disorder
      (n = 461)-defined as a positive screen for posttraumatic stress disorder, major
      depressive disorder, or alcohol misuse-20.2% reported talking to a "pastoral
      counselor" in the preceding year, 44.7% reported talking to a mental health
      professional, and 46.6% reported talking to neither. In a multivariate analysis
      for veterans with a probable mental disorder, seeing a pastoral counselor was
      associated with an increased likelihood of seeing a mental health professional in
      the past year (OR: 2.16; 95% CI: [1.28, 3.65]). In a separate bivariate analysis,
      pastoral counselors were more likely to be seen by veterans who indicated
      concerns about stigma or distrust of mental health care. These results suggest
      that pastoral and mental health care services may complement one another and
      underscore the importance of enhancing understanding and collaboration between
      these disciplines so as to meet the needs of the veterans they serve.

PMID- 24933107
TI  - A meta-analysis of cognitive functioning in nondemented adults with type 2
      diabetes mellitus.
AB  - OBJECTIVE: The current investigation sought to determine the pattern and
      magnitude of cognitive functioning deficits in persons with type 2 diabetes
      mellitus without dementia using meta-analysis to consolidate findings in the
      literature. METHODS: MedLine and PsychInfo databases were searched to identify
      studies of cognitive functioning in persons with type 2 diabetes. Effect sizes
      (Cohen's d) were calculated for the differences in cognitive functioning between
      subjects with type 2 diabetes and controls without diabetes on classified
      cognitive abilities. Average d values were calculated for all cognitive abilities
      across studies. RESULTS: Twenty-five studies meeting the inclusion criteria were
      identified. Persons with type 2 diabetes performed significantly lower than
      controls without diabetes (p<0.05) on all cognitive abilities evaluated, with
      effect sizes ranging from -0.14 to -0.37. The largest effect sizes were
      processing speed (with motor task demands), M -0.37 (95% CI, -0.41 to -0.32), and
      divided attention/shifting, M -0.36 (95% CI, -0.42 to -0.31). CONCLUSIONS: Type 2
      diabetes leads to mild to moderate deficits in all measured cognitive abilities.
      There was a lack of published studies investigating type 2 diabetes-associated
      variables; therefore, additional meta-analyses investigating the impact of these
      variables on cognitive functioning in type 2 diabetes could not be performed. As
      such, data from individual studies must be reported consistently to allow for
      investigation of variables that may affect the relationship between type 2
      diabetes and cognitive functioning. Given the present findings, clinicians
      working with patients with type 2 diabetes should be alerted to the possibility
      of cognitive changes that could impact type 2 diabetes treatment management or
      require referral for neuropsychological assessment.

PMID- 24933106
TI  - Effect of atorvastatin on pancreatic Beta-cell function and insulin resistance in
      type 2 diabetes mellitus patients: a randomized pilot study.
AB  - OBJECTIVE: Statins are commonly used for the management of dyslipidemia in type 2
      diabetes mellitus patients. We hypothesized that atorvastatin could modulate the
      beta-cell function by altering the levels of proapoptotic and antiapoptotic
      lipoproteins and could also have an effect on insulin resistance. The aim of the
      present pilot study was to assess the effect of atorvastatin 10 mg on pancreatic
      beta-cell function and insulin resistance in patients with hyperlipidemia and
      type 2 diabetes by using the homeostasis model assessment-2 (HOMA2) index.
      METHODS: Fifty-one type 2 diabetes patients receiving oral antidiabetes drugs,
      not taking statins, with baseline low-density lipoprotein cholesterol between 2.6
      mmol/L and 4.1 mmol/L were included. Forty-three patients (21 in placebo group
      and 22 in atorvastatin group) completed the study and were taken up for final
      analysis. Fasting blood samples were obtained at baseline and at 12 weeks to
      determine levels of blood glucose, lipid profile, insulin, C-peptide and
      glycosylated hemoglobin (A1C). RESULTS: Atorvastatin nonsignificantly increased
      fasting serum insulin (+14.29%, p=0.18), accompanied by marginal nonsignificant
      increases in fasting plasma glucose and A1C. There was a decrease in HOMA2
      percent beta-cell function (-2.9%, p=0.72) and increase in HOMA2 insulin
      resistance (+14%, p=0.16) in the atorvastatin group as compared with baseline,
      but the difference was not statistically significant. CONCLUSIONS: Atorvastatin
      in the dose used failed to produce significant change in pancreatic beta-cell
      function and insulin resistance in type 2 diabetes patients as assessed by the
      HOMA2 index. The possible explanations include absence of lipotoxicity at
      prevailing levels of dyslipidemia at baseline or inadequacy of statin dose used
      in the study. (Clinical Trials Registry-India: CTRI/2008/091/000099).

PMID- 24933108
TI  - Food and physical activity behaviours of adults attending a prediabetes education
      class.
AB  - OBJECTIVES: The primary objective of this study was to examine food and physical
      activity behaviours of adults with prediabetes. METHODS: For this cross-sectional
      study, adults (aged >17 years) with prediabetes (n=1228) who attended a
      prediabetes education class were recruited. Participants self-administered an
      assessment of food and physical activity behaviours using the Food Behaviour
      Checklist and the Godin Leisure Time Exercise Questionnaire. Linear regression
      models were performed to identify significant relationships between food,
      physical activity, age, body mass index and food access variables. RESULTS:
      Participants were 35.8% men with a mean age of 57.7 years (SD 11.6) and 64.2%
      women with a mean age of 55.2 years (13.9). Neither group was consuming adequate
      fruits and vegetables (17.1% for men and 29.2% for women eating 5 or more
      servings a day) or meeting physical activity guidelines of 150 minutes (29.5% for
      men and 26.2% for women). Approximately 29.0% of the entire sample "always"
      consumed milk or soy products. Men reported higher saturated fat intakes than
      women. For the entire sample, 83.4% rated their diet quality as needing
      improvement, and most consumed sweetened beverages (71.1% of men and 50.9% of
      women). Many participants (88.5%) used nutrition facts panels to choose foods.
      Food behaviour subscales and physical activity were significantly associated with
      each other and with age, body mass index and food access (p<0.05). CONCLUSIONS:
      Overall, adults with prediabetes reported less than optimal food and physical
      activity behaviours. Evaluation of lifestyle behaviours using simple tools like
      the Food Behaviour Checklist and Godin Leisure Time Exercise Questionnaire can be
      helpful for program design, evaluation and delivery.

PMID- 24933109
TI  - Modular isotopomer synthesis of gamma-hydroxybutyric acid for a quantitative
      analysis of metabolic fates.
AB  - Herein we report a study combining metabolomics and mass isotopomer analysis used
      for investigation of the biochemical fate of gamma-hydroxybutyric acid (GHB).
      Using various (13)C incorporation labeling patterns into GHB, we have discovered
      that GHB is catabolized by previously unknown processes that include (i) direct
      beta-oxidation to acetyl-CoA and glycolate, (ii) alpha-oxidation to 3
      hydroxypropionyl-CoA and formate, and (iii) cleavage of C-4 to yield 3
      hydroxypropionate and CO2. We further utilized the unique attributes of our
      labeling patterns and the resultant isotopomers to quantitate relative flux down
      the identified pathways. 

PMID- 24933111
TI  - Effects of deafness and cochlear implant use on temporal response characteristics
      in cat primary auditory cortex.
AB  - We have previously shown that neonatal deafness of 7-13 months duration leads to
      loss of cochleotopy in the primary auditory cortex (AI) that can be reversed by
      cochlear implant use. Here we describe the effects of a similar duration of
      deafness and cochlear implant use on temporal processing. Specifically, we
      compared the temporal resolution of neurons in AI of young adult normal-hearing
      cats that were acutely deafened and implanted immediately prior to recording with
      that in three groups of neonatally deafened cats. One group of neonatally
      deafened cats received no chronic stimulation. The other two groups received up
      to 8 months of either low- or high-rate (50 or 500 pulses per second per
      electrode, respectively) stimulation from a clinical cochlear implant, initiated
      at 10 weeks of age. Deafness of 7-13 months duration had no effect on the
      duration of post-onset response suppression, latency, latency jitter, or the
      stimulus repetition rate at which units responded maximally (best repetition
      rate), but resulted in a statistically significant reduction in the ability of
      units to respond to every stimulus in a train (maximum following rate). None of
      the temporal response characteristics of the low-rate group differed from those
      in acutely deafened controls. In contrast, high-rate stimulation had diverse
      effects: it resulted in decreased suppression duration, longer latency and
      greater jitter relative to all other groups, and an increase in best repetition
      rate and cut-off rate relative to acutely deafened controls. The minimal effects
      of moderate-duration deafness on temporal processing in the present study are in
      contrast to its previously-reported pronounced effects on cochleotopy. Much
      longer periods of deafness have been reported to result in significant changes in
      temporal processing, in accord with the fact that duration of deafness is a major
      factor influencing outcome in human cochlear implantees. 

PMID- 24933110
TI  - Myo-inositol in Down syndrome amniotic fluid. A case-control study.

PMID- 24933114
TI  - The economic implications of multiple pregnancy following ART.
AB  - The clinical risks to mothers and babies associated with assisted reproductive
      technology (ART) multiple birth pregnancies are well described and widely
      recognized. In contrast, the long-term economic consequences that follow are less
      appreciated. The few economic analyses that do exist consistently demonstrate the
      greater patient, healthcare and societal costs associated with twins and higher
      order multiples when compared with singleton infants, and convincingly add to the
      argument that single embryo transfer should be standard practice in most patient
      groups. Several recent studies have shown that the relative price paid by
      patients for ART treatment not only has implications for who can afford to access
      treatment, but also plays an important role in incentivizing embryo transfer
      practices and thus ART multiple birth rates. This review summarizes the current
      literature on the costs and consequences of ART multiple births, the contribution
      of ART multiple births to the economic burden associated with preterm birth, the
      evidence for the cost-effectiveness of single embryo transfer, and the
      association between the cost of treatment and the downstream costs associated
      with multiple births. 

PMID- 24933113
TI  - Myc and its interactors take shape.
AB  - The Myc oncoprotein is a key contributor to the development of many human
      cancers. As such, understanding its molecular activities and biological functions
      has been a field of active research since its discovery more than three decades
      ago. Genome-wide studies have revealed Myc to be a global regulator of gene
      expression. The identification of its DNA-binding partner protein, Max, launched
      an area of extensive research into both the protein-protein interactions and
      protein structure of Myc. In this review, we highlight key insights with respect
      to Myc interactors and protein structure that contribute to the understanding of
      Myc's roles in transcriptional regulation and cancer. Structural analyses of Myc
      show many critical regions with transient structures that mediate protein
      interactions and biological functions. Interactors, such as Max, TRRAP, and PTEF
      b, provide mechanistic insight into Myc's transcriptional activities, while
      others, such as ubiquitin ligases, regulate the Myc protein itself. It is
      appreciated that Myc possesses a large interactome, yet the functional relevance
      of many interactors remains unknown. Here, we discuss future research trends that
      embrace advances in genome-wide and proteome-wide approaches to systematically
      elucidate mechanisms of Myc action. This article is part of a Special Issue
      entitled: Myc proteins in cell biology and pathology. 

PMID- 24933115
TI  - Ultrastructural study of electron dense deposits in renal tubular basement
      membrane: prevalence and relationship to epithelial atrophy.
AB  - This study reports the prevalence of immune deposits associated with the proximal
      and distal tubules in a series of routine renal biopsies received in our
      department during a single calendar year. From 87 cases, 65 (74%) were found to
      have glomerular immune deposits by immunofluorescence. Tubular immune deposits
      were found in 12 cases (18%), 3 of which had no glomerular deposits. By
      transmission electron microscopy (EM), 58 cases (66%) were found to have deposits
      of granular or vesicular material associated with the tubular basement membranes
      (TBM). Finely granular electron dense deposits appeared to correspond to the
      immune deposits seen by immunofluorescence microscopy (IF) and may be a sensitive
      marker of immune deposition.

PMID- 24933116
TI  - The effect of progesterone on genes involved in preterm labor.
AB  - The decidua is known to be a major source of intrauterine PGF2alpha during late
      gestation and labor, and inflammatory cytokines, including IL-1beta, IL-6, and IL
      8, are elevated in spontaneous preterm deliveries. In the present study, to
      elucidate how progesterone blocks the pathways associated with preterm birth, we
      determined the effects of P4 on the expression of PTGS-2 and PTGFR mRNA in human
      decidua fibroblast cells, as well as the genes, using microarray analysis.
      Senescence was induced in primary cultured human decidual cells treated with IL
      1beta. The IL-1beta treatment implicated by microarray analysis increased gene
      expression levels of PTGS-2, PTGFR, NFkappa-B p65, IL-17, and IL-8. In contrast,
      P4+IL-1beta decreased the expression levels of all of these genes in comparison
      to treatment with IL-1beta alone (p<0.05). IL-1beta also increased the proportion
      of SA-beta-gal-positive cells. Treatment with IL-1beta also increased the p21
      protein level in comparison to cells treated either with the vehicle or P4.
      Neither the p21 protein level nor the number of SA-beta-gal-positive cells was
      increased in normal endometrial glandular cells by IL-1beta (p<0.05). Our studies
      demonstrated that P4 changes the level of gene expression in a manner that favors
      an anti-inflammatory milieu. Because IL-8 appears to be the cytokine whose
      expression is most significantly modulated by P4, further studies evaluating IL-8
      as a therapeutic target are needed.

PMID- 24933117
TI  - Functional Toll-like receptors in primary first-trimester trophoblasts.
AB  - Toll-like receptors (TLRs) are an important part of the body's danger response
      system and crucial for initiating inflammation in response to cellular stress,
      tissue damage, and infections. Proper placental development is sensitive to
      inflammatory activation, and a role for TLRs in trophoblast immune activation has
      been suggested, but no overall examination has been performed in primary
      trophoblasts of early pregnancy. This study aimed to broadly examine cell surface
      and endosomal TLR gene expression and activation in first-trimester trophoblasts.
      Gene expression of all ten TLRs was examined by quantitative RT-PCR (RT-qPCR) in
      primary first-trimester trophoblasts (n = 6) and the trophoblast cell line BeWo,
      and cytokine responses to TLR ligands were detected by quantitative multiplex
      immunoassay. Primary first-trimester trophoblasts broadly expressed all ten TLR
      mRNAs; TLR1, TLR2, TLR3, TLR4, and TLR6 mRNA were expressed by all primary
      trophoblast populations, while TLR5, TLR7, TLR8, TLR9, and TLR10 mRNA expression
      was more restricted. Functional response to ligand activation of cell surface
      TLR2/1, TLR4, and TLR5 increased IL-6 and/or IL-8 release (P < 0.01) from primary
      trophoblasts. For endosomal TLRs, TLR3 and TLR9 ligand exposure increased
      receptor-specific production of IL-8 (P < 0.01) and IFN-gamma-induced protein 10
      (IP-10; P < 0.001) or vascular endothelial growth factor A (VEGFA; P < 0.01). In
      contrast, BeWo cells expressed lower TLR mRNA levels and did not respond to TLR
      activation. In conclusion, primary first-trimester trophoblasts broadly express
      functional TLRs, with inter-individual variation, suggesting that trophoblast
      TLR2, TLR3, TLR4, TLR5, and TLR9 might play a role in early placental
      inflammation.

PMID- 24933118
TI  - Impact of maternal cholesterol metabolism on ovarian follicle development and
      fertility.
AB  - The relationship among maternal lipid metabolism, fetal development, and adult
      disease of the offspring represents an emerging topic of high epidemiological
      relevance. The present review highlights the very early aspects of this process.
      Recent data suggest a link between lipid metabolism and reproduction/fertility,
      not only on the systemic level, but also locally on the level of the ovary that
      maintains its own sterol metabolism, likely in a self-regulated fashion.
      Follicular fluid - which surrounds oocytes in a developing follicle - contains
      all relevant lipoprotein subclasses that reach the follicular fluid either by
      diffusion, in the case of high-density lipoproteins (HDL), or by local production
      within the granulosa cells, in the case of very low-density lipoproteins (VLDL).
      Here, we summarize current knowledge on lipoprotein metabolism in the ovary in
      the context of fertility, and hypothesize that lipoproteins within follicular
      fluid are relevant to the development of the early embryo and thereby putatively
      also to the programming of metabolic disease later in life. 

PMID- 24933119
TI  - Perceived top 10 highly effective interventions to prevent adult inpatient fall
      injuries by specialty area: a multihospital nurse survey.
AB  - PURPOSE: This study identified the perceived top 10 highly effective
      interventions to prevent fall injuries of adult inpatients based on the
      perceptions of RN staff by specialty area in acute hospital settings. BACKGROUND:
      The fall prevention precautions to focus on may vary by patients' medical
      problems and thus by specialty area. METHODS: This cross-sectional nurse survey
      was conducted at five U.S. health systems (July 2011-February 2012, 68 study
      units, 10 specialty areas). 560 staff participants completed the survey, yielding
      an overall response rate of 25.81%. This work is part of a larger project.
      Descriptive statistics were used. RESULTS: Each specialty area had its own top 10
      effective interventions identified by RNs. The complexity and differences in the
      top 10 highly effective interventions by the 10 included specialty areas are
      apparent. For example, only one common intervention (keeping hospital bed brakes
      locked) appeared in the lists from the medical units and surgical units.
      CONCLUSION: Addressing the unique needs of the patient population by specialty
      area is essential. Adopting the perceived top 10 highly effective interventions
      for preventing injurious falls by specialty area with staff consensus might be
      more feasible for staff buy-in and compliance in inpatient acute care settings.
      Since patients' characteristics may change over time and the science in fall
      prevention is advancing, re-prioritizing effective interventions as needed every
      2 years is recommended.

PMID- 24933120
TI  - Role of vitamin D in ovarian physiology and its implication in reproduction: a
      systematic review.
AB  - OBJECTIVE: To report an update on the role of vitamin D (VD) in ovarian
      physiology with a focus on genes involved in steroidogenesis, follicular
      development, and ovarian reserve, as well as ovulatory dysfunction associated
      with polycystic ovary syndrome (PCOS), and ovarian response to assisted
      reproductive technology (ART). DESIGN: Systematic review. SETTING: Not
      applicable. PATIENT(S): Human, animal, and cell culture models. INTERVENTION(S):
      Pubmed literature search. MAIN OUTCOME MEASURE(S): Granulosa cell function, serum
      antimullerian hormone (AMH), AMH and its receptor gene expression, soluble
      receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART
      outcome. RESULT(S): In human granulosa cells, VD alters AMH signaling, FSH
      sensitivity, and progesterone production and release, indicating a possible
      physiologic role for VD in ovarian follicular development and luteinization. In
      the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and
      appropriate VD supplementation in VD-depleted women can suppress the seasonal
      changes that occur in serum AMH. In VD-deficient women with PCOS, VD
      supplementation lowers the abnormally elevated serum AMH levels, possibly
      indicating a mechanism by which VD improves folliculogenesis. The
      antiinflammatory sRAGE serum levels significantly increase in women with PCOS
      after VD replacement. Although follicular fluid 25OH-D correlates with IVF
      outcomes, there is a lack of data pertaining to the impact of VD supplementation
      on pregnancy rates following IVF. CONCLUSION(S): This review underscores the need
      for understanding the mechanistic actions of VD in ovarian physiology and the
      critical need for randomized trials to elucidate the impact of VD supplementation
      on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction
      associated with PCOS.

PMID- 24933121
TI  - Alternative views on setting clinical trial futility criteria.
AB  - A feature increasingly utilized in clinical trial practice is to allow a study to
      stop early when it seems unlikely to achieve its primary efficacy objectives.
      This is commonly referred to as stopping for futility, and can be motivated by
      ethical and financial considerations. A number of methods for addressing futility
      have been described in the literature, including rules based upon conditional
      power, predictive probability, beta spending functions, and others. We consider
      futility stopping from the point of view of quantifying and providing an
      objective sensible balance between risks of incorrect decisions (e.g., stopping
      trials which should continue, and continuing trials which should stop), and
      discuss how specific considerations within a trial can lead to choice of a
      sensible scheme. This approach is not specific to any particular scales in the
      literature such as those just mentioned, and we describe interrelationships among
      criteria expressed on different scales. As futility may be evaluated multiple
      times in a long-term trial and the amount of information available at scheduled
      interim analyses may be difficult to predict in advance, we present a specific
      optimality criterion and discuss which of the familiar scales tend to produce
      schemes simple to describe and implement, and with better behavior across
      different timepoints at which futility might be evaluated. 

PMID- 24933123
TI  - A node linkage approach for sequential pattern mining.
AB  - Sequential Pattern Mining is a widely addressed problem in data mining, with
      applications such as analyzing Web usage, examining purchase behavior, and text
      mining, among others. Nevertheless, with the dramatic increase in data volume,
      the current approaches prove inefficient when dealing with large input datasets,
      a large number of different symbols and low minimum supports. In this paper, we
      propose a new sequential pattern mining algorithm, which follows a pattern-growth
      scheme to discover sequential patterns. Unlike most pattern growth algorithms,
      our approach does not build a data structure to represent the input dataset, but
      instead accesses the required sequences through pseudo-projection databases,
      achieving better runtime and reducing memory requirements. Our algorithm
      traverses the search space in a depth-first fashion and only preserves in memory
      a pattern node linkage and the pseudo-projections required for the branch being
      explored at the time. Experimental results show that our new approach, the Node
      Linkage Depth-First Traversal algorithm (NLDFT), has better performance and
      scalability in comparison with state of the art algorithms. 

PMID- 24933125
TI  - Service users' priorities and preferences for treatment of psychosis: a user-led
      Delphi study.
AB  - OBJECTIVE: Service users may have different priorities and preferences for
      treatment compared with mental health professionals. Few studies have explored
      these potentially important differences. This study sought consensus from a
      sample of service users regarding priorities and preferences for treatment of
      psychosis. METHODS: A three-stage Delphi study exploring treatment priorities and
      preferences was conducted with a sample of mental health service users ("experts
      by experience"). After generation of an initial statement list (stage 1, N=6
      participants), 64 diverse elements of mental health treatment were rated during a
      two-stage online survey process (stage 2, N=32; stage 3, N=21). RESULTS: Fifteen
      of 64 treatment-related statements were endorsed as important or essential
      treatment priorities or preferences by more than 80% of participants during stage
      2. Two further statements were similarly endorsed during stage 3. CONCLUSIONS:
      This study is among the first of its kind and highlights the importance of
      assessing individual treatment priorities.

PMID- 24933124
TI  - A golden gate modular cloning toolbox for plants.
AB  - Plant Synthetic Biology requires robust and efficient methods for assembling
      multigene constructs. Golden Gate cloning provides a precision module-based
      cloning technique for facile assembly of multiple genes in one construct. We
      present here a versatile resource for plant biologists comprising a set of
      cloning vectors and 96 standardized parts to enable Golden Gate construction of
      multigene constructs for plant transformation. Parts include promoters,
      untranslated sequences, reporters, antigenic tags, localization signals,
      selectable markers, and terminators. The comparative performance of parts in the
      model plant Nicotiana benthamiana is discussed. 

PMID- 24933122
TI  - Common carotid intima media thickness and ankle-brachial pressure index correlate
      with local but not global atheroma burden: a cross sectional study using whole
      body magnetic resonance angiography.
AB  - BACKGROUND: Common carotid intima media thickness (CIMT) and ankle brachial
      pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have
      been shown to correlate with arterial stiffness, however their correlation with
      global atherosclerotic burden has not been previously assessed. We compare CIMT
      and ABPI with atheroma burden as measured by whole body magnetic resonance
      angiography (WB-MRA). METHODS: 50 patients with symptomatic peripheral arterial
      disease were recruited. CIMT was measured using ultrasound while rest and
      exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4
      volume acquisitions with a divided dose of intravenous gadolinium gadoterate
      meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical
      arterial segments with each scored according to degree of luminal narrowing: 0 =
      normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment
      scores were summed and from this a standardized atheroma score was calculated.
      RESULTS: The atherosclerotic burden was high with a standardised atheroma score
      of 39.5+/-11. Common CIMT showed a positive correlation with the whole body
      atheroma score (beta 0.32, p = 0.045), however this was due to its strong
      correlation with the neck and thoracic segments (beta 0.42 p = 0.01) with no
      correlation with the rest of the body. ABPI correlated with the whole body
      atheroma score (beta -0.39, p = 0.012), which was due to a strong correlation
      with the ilio-femoral vessels with no correlation with the thoracic or neck
      vessels. On multiple linear regression, no correlation between CIMT and global
      atheroma burden was present (beta 0.13 p = 0.45), while the correlation between
      ABPI and atheroma burden persisted (beta -0.45 p = 0.005). CONCLUSION: ABPI but
      not CIMT correlates with global atheroma burden as measured by whole body
      contrast enhanced magnetic resonance angiography in a population with symptomatic
      peripheral arterial disease. However this is primarily due to a strong
      correlation with ilio-femoral atheroma burden.

PMID- 24933126
TI  - Vitamin B12 deficiency in an adolescent girl with polycystic ovarian syndrome.

PMID- 24933127
TI  - Field electron emission of layered Bi2Se3 nanosheets with atom-thick sharp edges.
AB  - Field electron emission properties of solution processed few-layer Bi2Se3
      nanosheets are studied for the first time, which exhibit a low turn-on field of
      2.3 V MUm(-1), a high field enhancement factor of up to 6860 and good field
      emission stability. This performance is better than that of the as reported
      layered MoS2f sheets and is comparable to that of single layer graphene films.
      The efficient field emission behaviours are found to be not only attributed to
      their lower work function but also related to their numerous sharp edges or
      protrusion decorated structure based on our simulation results. Besides, the
      contribution of possible two-dimensional electron gas surface states of atom
      thick layered Bi2Se3 nanosheets is discussed in this paper. We anticipate that
      these solution processed layered Bi2Se3 nanosheets have great potential as robust
      high-performance vertical structure electron emitters for future light weight and
      highly flexible vacuum micro/nano-electronic device applications.

PMID- 24933128
TI  - Pressure-voltage trap for DNA near a solid-state nanopore.
AB  - We report the formation of a tunable single DNA molecule trap near a solid-state
      nanopore in an electrolyte solution under conditions where an electric force and
      a pressure-induced viscous flow force on the molecule are nearly balanced.
      Trapped molecules can enter the pore multiple times before escaping the trap by
      passing through the pore or by diffusing away. Statistical analysis of many
      individually trapped molecules yields a detailed picture of the fluctuation
      phenomena involved, which are successfully modeled by a one-dimensional first
      passage approach. 

PMID- 24933129
TI  - STAT4 deficiency protects against neointima formation following arterial injury
      in mice.
AB  - Signal transducer and activator of transcription 4 (STAT4) has been associated
      with susceptibility to autoimmune diseases. Intriguingly, we previously reported
      that STAT4 might play a critical role in vascular smooth muscle cell (VSMC)
      proliferation. The present study therefore investigated the impact of STAT4 on
      VSMC migration, apoptosis and neointimal hyperplasia postinjury, as well as the
      underlying mechanisms. Guide-wire injury was associated with development of
      intimal neointima, STAT4 and phosphorylated STAT4 (p-STAT4) expressions were
      apparently up-regulated in the injured arteries. Neointima was greatly blocked in
      STAT4 knockout (KO) mice compared with wild type (WT) mice. A marked loss of
      inflammatory cells was identified in the vasculature postinjury in STAT4 KO mice.
      VSMC apoptosis was enhanced in the vasculature postinjury in STAT4 KO mice
      compared with WT mice. Cultured primary STAT4 KO VSMCs displayed reduced
      migration in comparison with WT controls. Mechanically, the deletion of STAT4
      potently decreased the level of MCP-1, and its downstream targets MMP1 and MMP2.
      The effect of STAT4 on VSMC apoptosis was mainly mediated by the activation of
      the mitochondrial apoptotic pathway, as manifested by increased cytochrome c
      release and the activation of caspase-3. STAT4 therefore represents a promising
      molecular target to limit restenosis after artery intervention. 

PMID- 24933130
TI  - Genetic epidemiology of cancer predisposition DNA repair genes is probably
      related with ancestral surviving under adverse environmental conditions.
AB  - AIMS: Surviving under a stressful environment may be a real challenge.
      Individuals (and their offspring) with accumulated genetic variation in their DNA
      repair genes may have a higher probability to survive under these conditions. A
      partially unstable DNA repair system raises the mutagenesis rate and the
      probability for an advantageous mutation to appear. This can also explain the
      high incidence of specific types of cancer today. The aim of this study was to
      find evidence for this phenomenon in humans, trying in this way to explain the
      cancer rates that differ worldwide and especially the breast and colon cancer
      ones. RESULTS: The last ice age (last glacial maximum) is probably the most
      recent example of extreme environmental conditions that existed in many regions
      of our planet. Careful comparison of the last ice age Earth map with the cancer
      incidence maps of the GLOBOCAN project revealed a high similarity. Human
      populations that survived in those regions may indeed have a partially defective
      DNA repair system. Adding on to this observation, an evolutionary model is
      proposed here for how populations escape extinction, where cancer may have been
      increased in modern humans due to an evolutionary site effect. CONCLUSION: A
      novel explanation is proposed for the high cancer incidence in specific
      geographic regions, based on epidemiological observations and on the assumption
      for unstable DNA repair in ancestral individuals.

PMID- 24933131
TI  - Shorter dispatcher-assisted CPR time-to-compression using the latest dispatch
      protocol.

PMID- 24933132
TI  - Reply to letter: shorter dispatcher-assisted CPR time-to-compression using the
      latest dispatch protocol.

PMID- 24933134
TI  - Impact of expectations on the effects of exercise on psychological distress.
AB  - OBJECTIVE: To evaluate the influence of expectations on effectiveness of exercise
      in reducing psychological distress. METHOD: Data came from a Swedish longitudinal
      population-based study consisting of 4631 people aged 20-64 years. Psychological
      distress was measured with the Major Depressive Inventory. Expectations (positive
      expectations or indifference) towards exercise were combined with exercise
      (regular exercise: yes or no). RESULTS: Indifferent non-exercisers had increased
      risk of psychological distress. Regular exercisers who were indifferent towards
      exercise as a self-help method were less likely to be psychologically distressed
      compared to exercisers with positive expectations. CONCLUSION: The results
      encourage systematic use of exercise in prevention and rehabilitation of persons
      suffering from psychological distress. People's personal expectations might not
      be needed for treatment effect.

PMID- 24933133
TI  - Relationship between perceived discrimination and sedentary behavior in adults.
AB  - OBJECTIVE: To identify psychosocial factors associated with sedentary behavior,
      we tested whether perceived discrimination is associated with sedentary behavior.
      METHODS: Black and white men and women (N = 3270) from the Coronary Artery Risk
      Development in Young Adults (CARDIA) Study reported experiences of discrimination
      and time engaged in total and screen time sedentary behaviors in 2010-11.
      RESULTS: There were no associations of discriminatory experiences with total
      sedentary behavior time. However, discriminatory experiences were positively
      associated with screen time for black men (OR 1.81, 95% CI: 1.14, 2.86) and white
      women (OR 1.51, 95% CI: 1.14, 2.00) after adjusting for demographic and
      traditional cardiovascular disease risk factors. CONCLUSION: Among black men and
      white women, discriminatory experiences were correlated with more screen time
      sedentary behavior.

PMID- 24933135
TI  - Does culture or illness change a smoker's perspective on cessation?
AB  - OBJECTIVES: To explore cultural context for smoking cessation within Chinese
      communities in Vancouver, and identify opportunities to support development of
      culturally appropriate resources for cessation. METHODS: Applied participatory
      approach involving community members, patients, and key-informants in the design
      and implementation of the research. RESULTS: Whereas many participants were
      motivated to quit, their perceptions of desire to do so were not supported by
      effective interventions and many attempts to quit were unsuccessful. CONCLUSION:
      Tobacco control clinics and care providers need to adopt culturally and
      linguistically relevant interventions to facilitate behavioral modifications and
      cessation in ethnic minority communities.

PMID- 24933137
TI  - Smiles count but minutes matter: responses to classroom exercise breaks.
AB  - OBJECTIVES: To determine the subjective responses of teachers and students to
      classroom exercise breaks, and how responses varied by duration. METHODS: This
      mixed-methods experimental study included focus groups with teachers (N = 8) and
      4(th)- and 5(th)-grade students (N = 96). Students participated in 5-, 10-, and
      20-minute exercise breaks and 10 minutes of sedentary activity. In an additional
      exploratory analysis, video-tapes of each condition were coded and compared for
      positive affect. RESULTS: Students and teachers discussed multiple benefits, but
      teachers discussed barriers to implementing regular breaks of 5-minutes or more.
      Students exhibited higher positive affect during each exercise condition.
      CONCLUSIONS: Classroom exercise breaks are an enjoyable way to increase physical
      activity, but additional support may be needed to encourage teachers to implement
      breaks of 5 minutes or longer.

PMID- 24933138
TI  - Stigma and health literacy: an agenda for advancing research and practice.
AB  - OBJECTIVES: To propose a framework addressing various factors contributing to
      stigma associated with low health literacy, how stigma is manifested, and how it
      may contribute to adverse health consequences. METHOD: The framework incorporated
      concepts found in existing empirical research on stigmatized health conditions
      with an emphasis on concealable conditions such as mental health, HIV status, and
      some chronic illnesses. RESULTS: Pursuing the proposed research agenda would
      provide a better understanding of the various factors contributing to stigma
      associated with low health literacy, how that stigma is manifested, and how it
      may contribute to adverse health consequences. CONCLUSION: The goal of proposing
      a wide-ranging research agenda is to encourage research that will inform the
      development of a comprehensive framework that addresses factors that influence
      stigma associated with health literacy from multiple levels: micro, meso, and
      macro.

PMID- 24933139
TI  - Predicting illness behavior: health anxiety mediated by locus of control.
AB  - OBJECTIVE: To examine the role of 3 dimensions of Health Locus of Control (HLOC)
      on the relationship between health anxiety and illness behavior. METHODS: Cross
      sectional survey study of 202 college women. Path analysis and bootstrapping
      techniques were used to test the significance of mediated models. RESULTS: The
      indirect effect of Powerful Others HLOC was significant (beta = .06, p < .001),
      and together health anxiety and Powerful Others HLOC explained 27% of the
      variance in illness behavior. CONCLUSION: Health anxiety and illness behavior are
      common problems in college women, and that Powerful Others HLOC is a key
      mechanism underlying the relationship between health anxiety and illness
      behavior.

PMID- 24933136
TI  - Novel incentives and messaging in an online college smoking intervention.
AB  - OBJECTIVES: To examine the feasibility, acceptability, and potential
      effectiveness of an online intervention targeting college smokers. The incentives
      involved discounted or free goods and services from businesses proximal to each
      campus. METHODS: A randomized controlled trial was conducted with 122 current
      smokers recruited from 2 Southeastern US universities. The intervention involved
      health behavior monitoring, targeted messaging, and incentives for healthy goods
      and services versus the American Cancer Society's Guide to Quitting Smoking
      online. RESULTS: The intervention achieved greater adherence and utilization (p's
      < .001). Overall, 55.6% learned about a local business through this program. At
      end-of-treatment, intervention participants less frequently attempted to quit (p
      = .02) but smoked fewer cigarettes/day (p = .05). Both groups demonstrated
      significant end-of-treatment cessation rates. CONCLUSIONS: This intervention
      demonstrated feasibility and acceptability.

PMID- 24933140
TI  - Does adolescent weight status predict problematic substance use patterns?
AB  - OBJECTIVES: To identify underlying patterns of cigarette smoking, alcohol use,
      and marijuana use in young adulthood, and ascertain whether adolescent overweight
      or obesity status predicts problematic substance use patterns. METHODS: The study
      included 15,119 participants from the National Longitudinal Study of Adolescent
      Health (Add Health) at Wave 1 (11-19 years) and Wave 3 (18-26 years). Latent
      class analysis was conducted. RESULTS: Participants were classified into a Low
      Substance Use (35%), Regular Smokers (12%), High-risk Alcohol use (33%), or High
      Substance Use (20%) class. Overweight/obese adolescents had a greater likelihood
      of belonging to the Regular Smokers class. CONCLUSIONS: Overweight/obese
      adolescents are at higher risk of engaging in regular cigarette smoking without
      problematic alcohol or marijuana use.

PMID- 24933142
TI  - Food-shopping environment disparities in Texas WIC vendors: a pilot study.
AB  - OBJECTIVE: To identify differences in food-shopping environments of Texas WIC
      vendors using a culturally adapted instrument. METHODS: A survey tool was
      developed for measuring food availability, accessibility, and affordability in
      111 WIC vendors in Texas. Two-tailed t-tests and Mann-Whitney tests were used for
      rural/urban and Texas-Mexico border/non-border area comparisons. RESULTS: Prices
      were higher in rural areas than in urban areas for 2 key foods, fruits (p = .024)
      and milk (p = .007); non-border vendors had overall better food availability than
      border vendors; non-border vendors had better accessibility for fruits (p = .007)
      than border vendors. CONCLUSION: In Texas, disparities in food-shopping
      environments are evident and can be assessed using a culturally adapted survey
      tool.

PMID- 24933141
TI  - Physical activity of preschool-aged Latino children in farmworker families.
AB  - OBJECTIVE: To describe time spent in sedentary and moderate-to-vigorous physical
      activity (MVPA) by children in Latino farmworker families and delineate sources
      of variation in sedentary and MVPA. METHOD: Data were from mother-child dyads (N
      = 248) in Latino farmworker households in North Carolina. Physical activity was
      assessed using accelerometers; mothers described their children's characteristics
      and their physical and social environments. RESULTS: Children spent 6.2 hours/day
      sedentary (Median=369 minutes), and 6.0 minutes/day in MVPA. Children in Head
      Start spent more time sedentary, whereas children living where dogs roam freely
      were less sedentary. Children whose mothers limited screen time spent 2 more
      minutes in MVPA. CONCLUSIONS: Preschool-aged Latino children in farmworker
      families are sedentary, engaging in little MVPA.

PMID- 24933143
TI  - Knowledge, attitudes, and beliefs of patients with chronic liver disease.
AB  - OBJECTIVES: To explore knowledge, attitudes, behaviors, and barriers to care
      among patients with chronic liver disease (CLD). METHODS: Three separate, one
      time-only, 60-minutes focus group sessions were audio-recorded, transcribed, and
      analyzed using an editing style of analysis. RESULTS: In total, 13 focus group
      participants provided 254 discrete comments. Emerging themes included: negative
      lifestyles/behaviors, lack of CLD knowledge, negative attitudes/emotions, stigma
      and negativity, health insurance, inaccessible/high cost medical care,
      drug/alcohol abuse, and discriminately sharing CLD diagnoses. CONCLUSIONS:
      Participants felt lack of CLD knowledge was a key factor in how patients
      perceived prevention, risks, causes, and treatment. These findings contribute to
      the important, yet limited, base of knowledge about CLD and provide a benchmark
      for future, more extensive studies and interventions.

PMID- 24933144
TI  - Factors related to hepatitis B screening among Africans in New York City.
AB  - OBJECTIVE: To understand factors that US Africans identify as barriers and
      facilitators for accessing hepatitis B (HBV) screening. METHODS: In-depth
      interviews were conducted and guided by the PEN-3 model to elicit culturally
      driven information in minority communities. RESULTS: Interviews were conducted
      with 22 US Africans. Salient themes that emerged were HBV knowledge, complexity
      of the US medical system, unaccustomed to preventive care, language and health
      literacy, availability and accessibility of screening, fear of disclosure,
      reliance on faith community, stigma of HBV, primacy towards a higher power on
      illnesses, and social systems influences. CONCLUSIONS: Findings were consistent
      with other at-risk populations, however, emphasis on privacy and fear of
      disclosure are distinct to Africans. This reinforces the need for a culturally
      targeted intervention for this at-risk population.

PMID- 24933145
TI  - Women's perspectives on smoking and pregnancy and graphic warning labels.
AB  - OBJECTIVES: To explore women's knowledge, attitudes, and beliefs about adverse
      outcomes associated with smoking during pregnancy and which outcomes might
      motivate cessation; to explore reactions to graphic warnings depicting 2 adverse
      outcomes. METHODS: Twelve focus groups were conducted with women of childbearing
      age who were current smokers. RESULTS: Participants had low to moderate awareness
      of many outcomes and believed it was acceptable to smoke in the first trimester
      before knowledge of pregnancy. Perceived susceptibility to outcomes was low.
      Motivators included risk-focused information, especially serious risks to the
      baby (eg, stillbirth, SIDS). Graphic warnings produced strong reactions,
      especially the warning with a real photo. CONCLUSIONS: Despite barriers to
      reducing rates of smoking during pregnancy, educational information and photos
      depicting babies' risks could motivate women to quit.

PMID- 24933146
TI  - Weight misperception and health risk behaviors in youth: the 2011 US YRBS.
AB  - OBJECTIVES: To evaluate dose-response associations between misperceived weight
      and 32 health risk behaviors in a nationally representative sample of US
      adolescents. METHODS: Participants included 13,864 US high school students in the
      2011 Youth Risk Behavior Survey. Comparing the degree of agreement between
      perceived and reported actual weight, weight misperception was determined as 5
      categories. Multivariable-adjusted logistic regression analyses evaluated
      associations of weight misperception with 32 health risk behaviors. RESULTS: Both
      underestimated and overestimated weight were statistically significantly
      associated with all 32 health risk behaviors in a dose-response manner after
      adjustment for age, sex and race/ethnicity, where greater weight misperception
      was associated with higher engagement in health risk behaviors. CONCLUSIONS:
      Understanding potential impacts of weight misperception on health risk behaviors
      could improve interventions that encourage healthy weight perception and
      attainment for adolescents.

PMID- 24933147
TI  - Barriers to dental services for older adults.
AB  - OBJECTIVE: To explore barriers to older adults' accessing dental care. METHODS:
      We performed oral exams on 184 community-dwelling older adults; those who needed
      dental care were contacted 6-12 weeks later to determine if they were able to
      access treatment. Those who could not access care were interviewed regarding
      barriers. RESULTS: Of those examined, 89% needed dental treatment. After 6 weeks,
      52% had received treatment, 48% had not. Those unable to access treatment had
      fewer teeth, were more likely to be referred regarding dentures, and were less
      likely to have a dentist. Reasons cited for not accessing care among the 35
      participants we interviewed included a lack of finances, transportation, or
      assistance in navigating dental service. CONCLUSIONS: Older adults have a high
      burden of oral disease and access barriers remain.

PMID- 24933148
TI  - Peer support enhanced social support in adolescent females during weight loss.
AB  - OBJECTIVES: To describe the development of a peer support intervention and test
      an enhanced version compared to a standard protocol. METHODS: Participants (N =
      36 females) were assigned to an Enhanced Peer Support (PS) vs Standard weight
      loss group for 4 months. The PS component consisted of skills training and
      practice between sessions using social networking. RESULTS: The PS group
      perceived significantly more peer support and experienced higher levels of social
      interaction. When meeting frequency decreased, the PS group showed an increase in
      overall types of support from group members. CONCLUSIONS: Findings suggest that
      an intervention targeting peer support skills results in greater feelings of peer
      support.

PMID- 24933150
TI  - Organic acids tunably catalyze carbonic acid decomposition.
AB  - Density functional theory calculations predict that the gas-phase decomposition
      of carbonic acid, a high-energy, 1,3-hydrogen atom transfer reaction, can be
      catalyzed by a monocarboxylic acid or a dicarboxylic acid, including carbonic
      acid itself. Carboxylic acids are found to be more effective catalysts than
      water. Among the carboxylic acids, the monocarboxylic acids outperform the
      dicarboxylic ones wherein the presence of an intramolecular hydrogen bond hampers
      the hydrogen transfer. Further, the calculations reveal a direct correlation
      between the catalytic activity of a monocarboxylic acid and its pKa, in contrast
      to prior assumptions about carboxylic-acid-catalyzed hydrogen-transfer reactions.
      The catalytic efficacy of a dicarboxylic acid, on the other hand, is
      significantly affected by the strength of an intramolecular hydrogen bond.
      Transition-state theory estimates indicate that effective rate constants for the
      acid-catalyzed decomposition are four orders-of-magnitude larger than those for
      the water-catalyzed reaction. These results offer new insights into the
      determinants of general acid catalysis with potentially broad implications. 

PMID- 24933149
TI  - Proteomics of neuropathic pain: proteins and signaling pathways affected in a rat
      model.
AB  - The myriad proteins may be involved in the mechanisms underlying the development
      and maintenance of neuropathic pain, an extremely disabling condition that
      originates from pathology of the nervous system. To address the mechanisms, we
      here analyzed proteins and cellular networks in the dorsal spinal cord mediating
      pain processing in a well-established rat model of neuropathic pain induced by
      spinal nerve ligation (SNL). Labeling-based proteomic methods together with high
      resolution mass spectrometry for proteome analysis were applied. 38 proteins
      including synapsin 1 and microtubule-associated protein 2 were identified as
      differently expressed in the SNL group. Pathway analysis suggests that
      maladaptive changes in the levels of these proteins may contribute to abnormal
      synaptic transmission and neuronal intracellular signaling underlying the onset
      and development of neuropathic pain. 

PMID- 24933151
TI  - Care of the post-laryngectomy stoma #281.

PMID- 24933152
TI  - SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid
      tumors.
AB  - Mutations in the SMARCB1 gene are involved in several human tumor-predisposing
      syndromes. They were established as an underlying cause of the tumor suppressor
      syndrome schwannomatosis in 2008. There is a much higher rate of mutation
      detection in familial disease than in sporadic disease. We have performed
      extensive genetic testing on a cohort of familial and sporadic patients who
      fulfilled clinical diagnostic criteria for schwannomatosis. In our updated
      cohort, we identified novel mutations within the SMARCB1 gene as well as several
      recurrent mutations. Of the schwannomatosis screens reported to date, including
      those in our updated cohort, SMARCB1 mutations have been found in 45% of familial
      probands and 9% of sporadic patients. The exon 1 mutation, c.41C>A p.Pro14His
      (10% in our series), and the 3' untranslated region mutation, c.*82C>T (27%), are
      the most common changes reported in patients with schwannomatosis to date,
      indicating the presence of mutation hot spots at both 5' and 3' portions of the
      gene. Comparison with germline SMARCB1 mutations in patients with rhabdoid tumors
      showed that the schwannomatosis mutations were significantly more likely to occur
      at either end of the gene and be nontruncating mutations (P < 0.0001). SMARCB1
      mutations are found in a significant proportion of schwannomatosis patients, and
      an even higher proportion of rhabdoid patients. Whereas SMARCB1 alone seems to
      account for rhabdoid disease, there is likely to be substantial heterogeneity in
      schwannomatosis even for familial disease. There is a clear genotype-phenotype
      correlation, with germline rhabdoid mutations being significantly more likely to
      be centrally placed, involve multiple exon deletions, and be truncating
      mutations. 

PMID- 24933154
TI  - Influence of fuel injection timing and pressure on in-flame soot particles in an
      automotive-size diesel engine.
AB  - The current understanding of soot particle morphology in diesel engines and their
      dependency on the fuel injection timing and pressure is limited to those sampled
      from the exhaust. In this study, a thermophoretic sampling and subsequent
      transmission electron microscope imaging were applied to the in-flame soot
      particles inside the cylinder of a working diesel engine for various fuel
      injection timings and pressures. The results show that the number count of soot
      particles per image decreases by more than 80% when the injection timing is
      retarded from -12 to -2 crank angle degrees after the top dead center. The late
      injection also results in over 90% reduction of the projection area of soot
      particles on the TEM image and the size of soot aggregates also become smaller.
      The primary particle size, however, is found to be insensitive to the variations
      in fuel injection timing. For injection pressure variations, both the size of
      primary particles and soot aggregates are found to decrease with increasing
      injection pressure, demonstrating the benefits of high injection velocity and
      momentum. Detailed analysis shows that the number count of soot particles per
      image increases with increasing injection pressure up to 130 MPa, primarily due
      to the increased small particle aggregates that are less than 40 nm in the radius
      of gyration. The fractal dimension shows an overall decrease with the increasing
      injection pressure. However, there is a case that the fractal dimension shows an
      unexpected increase between 100 and 130 MPa injection pressure. It is because the
      small aggregates with more compact and agglomerated structures outnumber the
      large aggregates with more stretched chain-like structures. 

PMID- 24933153
TI  - First identification of resident and circulating fibrocytes in Dupuytren's
      disease shown to be inhibited by serum amyloid P and Xiapex.
AB  - Dupuytren's disease (DD) is a common progressive fibroproliferative disorder
      causing permanent digital contracture. Proliferative myofibroblasts are thought
      to be the cells responsible for DD initiation and recurrence, although their
      source remains unknown. DD tissue has also been shown to harbor mesenchymal and
      hematopoietic stem cells. Fibrocytes are circulating cells that show
      characteristics of fibroblasts and they express surface markers for both
      hematopoietic and mesenchymal stromal cells. Fibrocytes differentiate from
      peripheral CD14+ mononuclear cells, which can be inhibited by serum amyloid P
      (SAP). In this study we have demonstrated the presence of fibrocytes in DD blood
      and tissue, moreover we have evaluated the effects of SAP and Xiapex (Collagenase
      Clostridium histolyticum) on fibrocytes derived from DD. H&E staining showed
      typical Spindle shaped morphology of fibrocytes. FACS analysis based on a unique
      combination of 3 markers, revealed the increased presence of fibrocytes in blood
      and tissue of DD patients. Additionally, immunohistology of DD nodule and cord
      tissue showed the presence of collagen 1+/CD34+ cells. No difference in plasma
      SAP levels was observed between DD and control. Higher concentrations of SAP
      significantly inhibited fibrocytes differentiated from DD derived monocytes
      compared to control. DD fascia derived fibrocytes showed resistance to growth
      inhibition by SAP, particularly nodule derived fibrocytes showed robust growth
      even at higher SAP concentrations compared to control. DD derived fibrocytes were
      positive for typical fibrocyte dual markers, i.e. Collagen 1/LSP-1 and collagen
      1/CD34. Xiapex was more effective in inhibiting the growth of nodule derived
      cells compared to commercially available collagenase A. Our results show for the
      first time the increased presence of fibrocytes in DD patient's blood and disease
      tissue compared to control tissue. Additionally, we evaluate the response of
      these fibrocytes to SAP and Xiapex therapy. 

PMID- 24933155
TI  - ARHGAP22 localizes at endosomes and regulates actin cytoskeleton.
AB  - Rho small GTPases control cell morphology and motility through the rearrangement
      of actin cytoskeleton. We have previously shown that FilGAP, a Rac-specific GAP,
      binds to the actin-cross-linking protein Filamin A (FLNa) and suppresses Rac
      dependent lamellae formation and cell spreading. ARHGAP22 is a member of FilGAP
      family, and implicated in the regulation of tumor cell motility. However, little
      is known concerning the cellular localization and mechanism of regulation at the
      molecular level. Whereas FilGAP binds to FLNa and localizes to lamellae, we found
      that ARHGAP22 did not bind to FLNa. Forced expression of ARHGAP22 induced
      enlarged vesicular structures containing the endocytic markers EEA1, Rab5, and
      Rab11. Moreover, endogenous ARHGAP22 is co-localized with EEA1- and Rab11
      positive endosomes but not with trans-Golgi marker TNG46. When constitutively
      activated Rac Q61L mutant was expressed, ARHGAP22 is co-localized with Rac Q61L
      at membrane ruffles, suggesting that ARHGAP22 is translocated from endosomes to
      membrane ruffles to inactivate Rac. Forced expression of ARHGAP22 suppressed
      lamellae formation and cell spreading. Conversely, knockdown of endogenous
      ARHGAP22 stimulated cell spreading. Thus, our findings suggest that ARHGAP22
      controls cell morphology by inactivating Rac but its localization is not mediated
      by its interaction with FLNa. 

PMID- 24933157
TI  - Short-term memory development: differences in serial position curves between age
      groups and latent classes.
AB  - In studies on the development of cognitive processes, children are often grouped
      based on their ages before analyzing the data. After the analysis, the
      differences between age groups are interpreted as developmental differences. We
      argue that this approach is problematic because the variance in cognitive
      performance within an age group is considered to be measurement error. However,
      if a part of this variance is systematic, it can provide very useful information
      about the cognitive processes used by some children of a certain age but not
      others. In the current study, we presented 210 children aged 5 to 12 years with
      serial order short-term memory tasks. First we analyze our data according to the
      approach using age groups, and then we apply latent class analysis to form latent
      classes of children based on their performance instead of their ages. We display
      the results of the age groups and the latent classes in terms of serial position
      curves, and we discuss the differences in results. Our findings show that there
      are considerable differences in performance between the age groups and the latent
      classes. We interpret our findings as indicating that the latent class analysis
      yielded a much more meaningful way of grouping children in terms of cognitive
      processes than the a priori grouping of children based on their ages.

PMID- 24933158
TI  - R2oDNA designer: computational design of biologically neutral synthetic DNA
      sequences.
AB  - R2oDNA Designer is a web application that stochastically generates orthogonal
      sets of synthetic DNA sequences designed to be biologically neutral. Biologically
      neutral sequences may be used for directing efficient DNA assembly by overlap
      directed methods, as a negative control for functional DNA, as barcodes, or
      potentially as spacer regions to insulate biological parts from local context.
      The software creates optimized sequences using a Monte Carlo simulated annealing
      approach followed by the elimination of sequences homologous to host genomes and
      commonly used biological parts. An orthogonal set is finally determined by using
      a network elimination algorithm. Design constraints can be defined using either a
      web-based graphical user interface (GUI) or uploading a file containing a set of
      text commands. 

PMID- 24933156
TI  - Tracking endogenous amelogenin and ameloblastin in vivo.
AB  - Research on enamel matrix proteins (EMPs) is centered on understanding their role
      in enamel biomineralization and their bioactivity for tissue engineering. While
      therapeutic application of EMPs has been widely documented, their expression and
      biological function in non-enamel tissues is unclear. Our first aim was to screen
      for amelogenin (AMELX) and ameloblastin (AMBN) gene expression in mandibular
      bones and soft tissues isolated from adult mice (15 weeks old). Using RT-PCR, we
      showed mRNA expression of AMELX and AMBN in mandibular alveolar and basal bones
      and, at low levels, in several soft tissues; eyes and ovaries were RNA-positive
      for AMELX and eyes, tongues and testicles for AMBN. Moreover, in mandibular
      tissues AMELX and AMBN mRNA levels varied according to two parameters: 1)
      ontogenic stage (decreasing with age), and 2) tissue-type (e.g. higher level in
      dental epithelial cells and alveolar bone when compared to basal bone and dental
      mesenchymal cells in 1 week old mice). In situ hybridization and
      immunohistodetection were performed in mandibular tissues using AMELX KO mice as
      controls. We identified AMELX-producing (RNA-positive) cells lining the adjacent
      alveolar bone and AMBN and AMELX proteins in the microenvironment surrounding
      EMPs-producing cells. Western blotting of proteins extracted by non-dissociative
      means revealed that AMELX and AMBN are not exclusive to mineralized matrix; they
      are present to some degree in a solubilized state in mandibular bone and
      presumably have some capacity to diffuse. Our data support the notion that AMELX
      and AMBN may function as growth factor-like molecules solubilized in the aqueous
      microenvironment. In jaws, they might play some role in bone physiology through
      autocrine/paracrine pathways, particularly during development and stress-induced
      remodeling. 

PMID- 24933159
TI  - Reduction of carcinogenic 4(5)-methylimidazole in a caramel model system:
      influence of food additives.
AB  - The effect of various food additives on the formation of carcinogenic 4(5)
      methylimidazole (4-MI) in a caramel model system was investigated. The
      relationship between the levels of 4-MI and various pyrazines was studied. When
      glucose and ammonium hydroxide were heated, the amount of 4-MI was 556 +/- 1.3
      MUg/mL, which increased to 583 +/- 2.6 MUg/mL by the addition of 0.1 M of sodium
      sulfite. When various food additives, such as 0.1 M of iron sulfate, magnesium
      sulfate, zinc sulfate, tryptophan, and cysteine were added, the amount of 4-MI
      was reduced to 110 +/- 0.7, 483 +/- 2.0, 460 +/- 2.0, 409 +/- 4.4, and 397 +/-
      1.7 MUg/mL, respectively. The greatest reduction, 80%, occurred with the addition
      of iron sulfate. Among the 12 pyrazines, 2-ethyl-6-methylpyrazine with 4-MI
      showed the highest correlation (r = -0.8239). 

PMID- 24933160
TI  - Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM:
      the potential of combination strategies.
AB  - Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive
      tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which
      generate a network of disorganized, tortuous and permeable vessels. Recruitment
      of bone marrow derived cells (BMDC) is crucial for vasculogenesis. These cells
      may act as vascular progenitors by integrating into the newly formed blood
      vessels or as vascular modulators by releasing pro-angiogenic factors. In
      patients with recurrent GBM, anti-vascular endothelial growth factor (VEGF)
      therapy has been evaluated in combination with chemotherapy, yielding
      improvements in progression-free survival (PFS). However, benefits are temporary
      as vascular tumors acquire angiogenic pathways independently of VEGF.
      Specifically, acute hypoxia following prolonged VEGF depletion induces the
      recruitment of certain myeloid cell subpopulations, which highly contribute to
      treatment refractoriness. Here we review the molecular mechanisms of
      neovascularization in relation to bevacizumab therapy with special emphasis on
      the recruitment of BMDCs and possible combination therapies for GBM patients. 

PMID- 24933161
TI  - Genomic characterization of a novel picornavirus in Pekin ducks.
AB  - A novel picornavirus was detected from Pekin ducks (Anas platyrhynchos domestica)
      and completely sequenced. The virus was most closely related to megriviruses,
      with amino acid identities of 32-68%, 35-45%, 51-57%, 41-50%, and 61-63% in the
      P1, P2, P3, polyprotein, and 2C and 3CD regions, respectively. The virus was thus
      identified as an additional species in the genus Megrivirus and named Duck
      megrivirus (DMV). Sequence analyses indicated that the DMV genome possessed a
      megrivirus-like organization and also exhibited several unique features. The
      polyadenylated genome comprised 9700nt, one of the largest among known
      picornaviruses. A notable feature was the 2A region, which had an association of
      two distinct, function-unknown 2As (2A1 and 2A2) and a parechovirus-like 2A3. The
      5' untranslated region (UTR) contained a variant type IVB internal ribosome entry
      site (IRES), which possessed a long helix III4 ending with the "8"-like 20-nt
      long conserved structure at the top of domain III. The secondary structure model
      of inferred domain III of DMV-like IRES was also conserved in quail picornavirus,
      pigeon picornavirus B, and megriviruses. Domain II in DMV contained the conserved
      internal and apical loops previously identified in groups A and C of
      hepacivirus/pestivirus like IRESs. Moreover, DMV was closely related to different
      megriviruses in different genomic regions. These findings suggest that
      recombination events involving exchange of coding and noncoding regions may have
      occurred. DMV was detected in 28 of 117 (23.9%) ducks from four provinces in
      China, suggesting a high prevalence of DMV in duck populations. 

PMID- 24933162
TI  - Clinical and haematological characterisation of Mycoplasma suis infections in
      splenectomised and non-splenectomised pigs.
AB  - Mycoplasma suis causes infectious anaemia in pigs (IAP), which can manifest in
      various degrees of severity depending on the virulence and the host's
      susceptibility. As M. suis cannot be cultured in vitro experimental infections of
      splenectomised animals play an essential role for pathogenesis research. The aim
      of the present study was to characterise the course of experimental infection
      using the highly virulent and red blood cell (RBC-) invasive M. suis strain
      KI3806, to compare the experimental course in splenectomised and non
      splenectomised pigs and to correlate clinical and haematological parameters with
      M. suis blood loads. All infected splenectomised pigs (n=7) were PCR-positive 2
      days post infection (DPI) with maximum mean bacterial loads of 1.61 * 10(10)M.
      suis/mL on 8 DPI. They developed severe anaemia and massive hypoglycaemia by 8
      DPI and had to be euthanised preterm (until 8 DPI) without seroconversion. The
      non-splenectomised pigs (n=7) became PCR-positive within 23 DPI and reached a
      maximum mean M. suis load of 1.64 * 10(5)M. suis/mL on 8 DPI. They developed mild
      anaemia, massive skin alterations with petechiae and haemorrhagic diathesis and
      seroconverted within 35 DPI. The study demonstrated that experimental infection
      of splenectomised pigs with the highly virulent M. suis strain KI3806 induces a
      fulminant course of infection. In contrast, M. suis strain KI3806 induces a mild
      course of disease in non-splenectomised pigs, which resembles the situation in
      naturally infected pigs. Therefore, these infection models are valuable for
      future pathogenesis studies on acute and chronic M. suis infections.

PMID- 24933163
TI  - No contact transmission of avian bornavirus in experimentally infected cockatiels
      (Nymphicus hollandicus) and domestic canaries (Serinus canaria forma domestica).
AB  - Avian bornaviruses (ABV) are the causative agents of proventricular dilatation
      disease (PDD), a widely distributed disease of parrots. Distinct ABV lineages
      were also found in various non-psittacine avian species, such as canaries, but
      the pathogenic role of ABV in these species is less clear. Despite the wide
      distribution of ABV in captive parrots and canaries, its mode of transmission is
      poorly understood: both horizontal transmission via the urofaecal-oral route and
      vertical transmission are discussed to play a role. In this study we investigated
      pathology and horizontal transmission of ABV in domestic canaries (Serinus
      canaria forma domestica) and cockatiels (Nymphicus hollandicus), two natural host
      species commonly used for experimental ABV infections. ABV inoculation resulted
      in persistent infection of all inoculated animals from both species. ABV-infected
      cockatiels exhibited PDD-like symptoms, such as neurologic signs or shedding of
      undigested seeds. In contrast, infected domestic canaries did not develop
      clinical disease. Interestingly, we did not detect viral RNA in cloacal swabs and
      organ samples or ABV-specific antibodies in serum samples of contact-exposed
      sentinel birds from either species at any time during a four months observation
      period. Our results strongly indicate that horizontal transmission of ABV by
      direct contact is inefficient in immunocompetent fully fledged domestic canaries
      and cockatiels. 

PMID- 24933164
TI  - Should we always improve adherence to antimicrobial treatment? I don't think we
      should.

PMID- 24933165
TI  - Spatial relations of mercury contents in Pike (Esox lucius) and sediments
      concentration of the Anzali wetland, along the southern shores of the Caspian
      Sea, Iran.
AB  - In recent decades, the Anzali wetland has been threatened and destroyed by
      environmental pollution from several sources. The purpose of this study was to
      determine the possible relationships between mercury concentrations in Pike and
      their respective sediments within the assumed multiple activity center scales of
      Pike (100, 250 and 500 m in radius). To gain a better understanding spatial
      distribution pattern of Hg in sediments and to pursue the main purpose of this
      study, kriging (geostatistic spatial interpolation method) was applied. Poor
      relationships were found between mercury concentrations of Pike and sediments
      within the assumed multiple activity center scales of Pike. The mercury sediment
      influence diminished with the increasing radii of assumed activity centers. The
      results of the present study indicate that fish and sediment mercury
      concentrations in western parts of the Anzali wetland were low in comparison with
      the concentrations reported in the literature from other regions.

PMID- 24933166
TI  - Major factors influencing the elemental composition of surface estuarine
      sediments: the case of 15 estuaries in Portugal.
AB  - Upper sediments (0-5 cm) were sampled in 94 sites of water bodies of the fifteen
      Portuguese estuaries characterized by distinct settings of climate, topography
      and lithology, and marked by diverse anthropogenic pressures. Confined areas
      recognized as highly anthropogenic impacted, as well as areas dominated by
      erosion or frequently dredged were not sampled. Grain size, organic carbon
      (Corg), Al and trace elements (As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn) were
      determined. Normalisation of trace element concentrations to Al and Corg,
      correlations between elements and Principal Component Analysis (PCA) allowed
      identifying elemental associations and the relevance of grain-size, lithology and
      anthropogenic inputs on sediment chemical composition. Whereas grain-size is the
      dominant effect for the majority of the studied estuaries, the southern estuaries
      Mira, Arade and Guadiana are dominated by specific lithologies of their river
      basins, and anthropogenic effects are identified in Ave, Leca, Tagus and Sado.
      This study emphasizes how baseline values of trace elements in sediments may vary
      within and among estuarine systems.

PMID- 24933167
TI  - The endocannabinoid system and appetite: relevance for food reward.
AB  - Mounting evidence substantiates the central role of the endocannabinoid system
      (ECS) in the modulation of both homeostatic and hedonic elements of appetite and
      food intake. Conversely, feeding status and dietary patterns directly influence
      activity of the ECS. Following a general introduction on the functioning of the
      ECS, the present review specifically addresses its role in the modulation of
      hedonic eating. Humans possess strong motivational systems triggered by rewarding
      aspects of food. Food reward is comprised of two components: one appetitive
      (orienting towards food); the other consummatory (hedonic evaluation), also
      referred to as 'wanting' and 'liking', respectively. Endocannabinoid tone seems
      to influence both the motivation to feed and the hedonic value of foods, probably
      by modifying palatability. Human physiology underlying hedonic eating is still
      not fully understood. A better understanding of the role of the ECS in the
      rewarding value of specific foods or diets could offer new possibilities to
      optimise the balance between energy and nutrient intake for different target
      groups. These groups include the obese and overweight, and potentially
      individuals suffering from malnutrition. Examples for the latter group are
      patients with disease-related anorexia, as well as the growing population of
      frail elderly suffering from persistent loss of food enjoyment and appetite
      resulting in malnutrition and involuntary weight loss. It has become clear that
      the psychobiology of food hedonics is extremely complex and the clinical failure
      of CB1 inverse agonists including rimonabant (Accomplia(r)) has shown that 'quick
      wins' in this field are unlikely. 

PMID- 24933168
TI  - An investigation of implied Miranda waivers and Powell wording in a mock-crime
      study.
AB  - To guard against coerced self-incrimination, the Supreme Court of the United
      States outlined in Miranda v. Arizona (1966) what arresting officers must convey
      to custodial suspects for resulting statements to be admissible into evidence.
      During the ensuing decades, the Court has continued to grapple with the requisite
      wording and practical enforcement of these Constitutional rights. In Florida v.
      Powell (2010), the Court upheld the conviction of a defendant whose Miranda
      warning affirmed that before questioning he had the right to an attorney, but
      failed to specify that during questioning he had this right as well. In Berghuis
      v. Thompkins (2010), the Court ruled that the right to silence must be invoked
      explicitly, while valid Miranda waivers could be "implied" by a suspect's actions
      as well as words. The current study employed a mock crime design to assess the
      practical effects of these 2 rulings on waiver decisions. The wording change
      enabled by Powell had little effect on Miranda knowledge and reasoning. With
      regard to Thompkins, the type of waiver profoundly affected subsequent decisions:
      13.7% exercised their rights following implied waivers versus 81.1% with explicit
      waivers. Importantly, the implied waiver condition produced much higher
      percentages of confessions (17.6% vs. 3.8%) and of admissions about incriminating
      information (29.4% vs. 9.4%).

PMID- 24933169
TI  - Two sides of the same coin: gender harassment and heterosexist harassment in LGBQ
      work lives.
AB  - This project investigated the incidence, interplay, and impact of gender- and
      sexuality-based harassment, as experienced by lesbian, gay, bisexual, and queer
      (LGBQ) employees in higher education. Unlike much queer empirical research,
      participants in this study were residents of noncoastal regions of the U.S. that
      are predominantly White, rural, and conservative (i.e., "red states"). They
      completed surveys about their harassment experiences (gender harassment-sexist,
      gender harassment-policing, and heterosexist harassment), perceived support
      systems (from supervisors and organizations), and job attitudes (job burnout, job
      stress, and job satisfaction). Results showed that gender harassment-both sexist
      and policing subtypes-rarely occurred absent heterosexist harassment, and vice
      versa. Harassment severity (experiencing moderate to high levels of all three
      harassment types) was significantly associated with greater levels of job burnout
      (both disengagement and exhaustion) and job dissatisfaction. Even infrequent
      experiences of harassment related to large increases in the "threat" variety of
      job stress (i.e., sense of feeling hassled and overwhelmed on the job).
      Additionally, employees who perceived the lowest organizational support reported
      the most harassment. We interpret results in light of research on organizational
      behavior and LGBQ psychology. Moreover, we discuss our findings in the context of
      Title VII, currently interpreted to protect against harassment based on gender,
      sex, and sex stereotyping, but not sexual orientation. Our results can inform
      several possible avenues of expanding gay civil rights in employment: broadening
      judicial interpretations of Title VII, passing new legislation (e.g., the
      Employment Non-Discrimination Act, or ENDA), and strengthening organizational
      supports and policies that protect against sexuality-based abuses.

PMID- 24933170
TI  - Serious mental illness, criminal risk, parole supervision, and recidivism:
      testing of conditional effects.
AB  - Adults with serious mental illness (SMI) who are released from prison tend to
      recidivate more quickly and at higher rates than similarly situated adults who do
      not have SMI. The current study examined whether this relationship with
      recidivism is mediated by criminal risk level and whether parole supervision can
      ameliorate the effects of SMI on recidivism. Findings indicate that SMI did
      exhibit a significant indirect effect with recidivism when considering its
      relationship with actuarially assessed risk. However, this indirect effect was
      not conditioned by whether the individual was released to parole; specifically
      release status did not moderate the relationship between risk and recidivism. The
      direct effects of SMI on recidivism were found to be conditioned upon release
      status. Specifically, we found no relationship between SMI and recidivism for
      parolees and a negative relationship between SMI and recidivism among
      nonparolees. Findings indicate a need for paroling authorities to find more
      effective ways of reducing criminal risk, which can decrease subsequent
      recidivism, among the individuals they supervise.

PMID- 24933171
TI  - Changes in dynamic risk and protective factors for violence during inpatient
      forensic psychiatric treatment: predicting reductions in postdischarge community
      recidivism.
AB  - Empirical studies have rarely investigated the association between improvements
      on dynamic risk and protective factors for violence during forensic psychiatric
      treatment and reduced recidivism after discharge. The present study aimed to
      evaluate the effects of treatment progress in risk and protective factors on
      violent recidivism. For a sample of 108 discharged forensic psychiatric patients
      pre- and posttreatment assessments of risk (HCR-20) and protective factors
      (SAPROF) were compared. Changes were related to violent recidivism at different
      follow-up times after discharge. Improvements on risk and protective factors
      during treatment showed good predictive validity for abstention from violence for
      short- (1 year) as well as long-term (11 years) follow-up. This study
      demonstrates the sensitivity of the HCR-20 and the SAPROF to change and shows
      improvements on dynamic risk and protective factors are associated with lower
      violent recidivism long after treatment.

PMID- 24933172
TI  - A psychometric examination of treatment change in a multisite sample of treated
      Canadian federal sexual offenders.
AB  - In the present study, we examined the degree of change and predictive accuracy of
      a number of well-known psychological self-report measures intended to identify
      treatment targets for sexual offenders. Participants included 392 federally
      incarcerated sexual offenders who participated in low, moderate, or high
      intensity sexual offender programs offered within penitentiaries under the
      jurisdiction of the Correctional Service of Canada. These men were followed in
      the community for an average of 5.42 years postrelease. Very small to moderate
      pretreatment and posttreatment changes were found on measures of cognitive
      distortions, aggression/hostility, empathy, loneliness, social intimacy, and sex
      offender acceptance of responsibility. However, pretreatment and posttreatment
      scores on these measures frequently demonstrated weak and inconsistent
      relationships to sexual, violent, and general recidivism. In addition, within
      treatment change on these measures bore little relationship to outcome. However,
      when statistically corrected for pretreatment score the relationship of treatment
      change to outcome frequently improved, particularly on measures of physical
      aggression and anger, even after controlling for Static-99R score. Clinical and
      research implications are discussed regarding the assessment and evaluation of
      change on psychological risk factors in treated sexual offenders.

PMID- 24933173
TI  - Examining pretrial publicity in a shadow jury paradigm: issues of slant,
      quantity, persistence and generalizability.
AB  - The purpose of this study was to examine the influence of pretrial publicity
      (PTP) on mock juror decision making. Specifically, we examined the influence of
      quantity and slant of the PTP (proprosecution vs. prodefense), the persistence of
      PTP effects over time, and whether the PTP effects demonstrated in research
      laboratories would also occur in more naturalistic settings (generalizability).
      Using a shadow jury paradigm we examined these effects using a real trial as
      stimulus. Mock jurors included 115 jury-eligible community members who were
      naturally exposed to PTP in the venue in which the actual case occurred and 156
      who were experimentally exposed. We found mock jurors were significantly
      influenced by both the slant and quantity of the PTP to which they were exposed,
      such that those exposed to proprosecution or prodefense PTP tended to render
      decision in support of the party favored in the PTP, and those exposed to greater
      quantities of PTP tended to be more biased. Additionally, PTP effects persisted
      throughout the course of the trial and continued to influence judgments in face
      of trial evidence and arguments. A finding of no significant difference in the
      effect of exposure slant between the naturally exposed and experimentally exposed
      samples provides support for the external validity of laboratory studies
      examining PTP effects. This research helps address some of the concerns raised by
      courts with regard to the durability of PTP effects and the application of
      laboratory findings to real world settings.

PMID- 24933174
TI  - "So, what is a psychopath?" Venireperson perceptions, beliefs, and attitudes
      about psychopathic personality.
AB  - This study surveyed over 400 individuals attending jury duty regarding various
      perceptions, attitudes, and beliefs they had concerning psychopathic personality
      (psychopathy). The protocol included (a) prototype ratings of what participants
      considered to be core features, using the Comprehensive Assessment of
      Psychopathic Personality (CAPP) prototype rating scale; (b) questions concerning
      knowledge and beliefs about psychopathy (e.g., prevalence in society); and (c)
      attitudinal scales concerning potential associated features (e.g., criminality,
      rehabilitation potential), etiological underpinnings, and moral judgments and
      legal sanctions. Consistent with results of earlier studies using expert raters,
      jury panel members rated most of the 33 individual CAPP items and all 6 CAPP
      scales as at least moderately prototypical, with Self and Dominance domains
      obtaining the highest mean ratings. Many participants also strongly endorsed
      symptoms of psychosis (e.g., delusions) as prototypical of psychopathy. Despite
      this, they viewed psychopaths as responsible for their own actions, as capable of
      determining right from wrong, and as generally not "insane." Our findings
      indicate that jury panel members view the prototypical psychopath as highly
      dominant, self-focused, and lacking in remorse and empathy and reinforce the need
      for expert witnesses to clearly differentiate between psychopathy and psychotic
      spectrum disorders.

PMID- 24933175
TI  - Double-blind photo lineups using actual eyewitnesses: an experimental test of a
      sequential versus simultaneous lineup procedure.
AB  - Eyewitnesses (494) to actual crimes in 4 police jurisdictions were randomly
      assigned to view simultaneous or sequential photo lineups using laptop computers
      and double-blind administration. The sequential procedure used in the field
      experiment mimicked how it is conducted in actual practice (e.g., using a
      continuation rule, witness does not know how many photos are to be viewed,
      witnesses resolve any multiple identifications), which is not how most lab
      experiments have tested the sequential lineup. No significant differences emerged
      in rates of identifying lineup suspects (25% overall) but the sequential
      procedure produced a significantly lower rate (11%) of identifying known-innocent
      lineup fillers than did the simultaneous procedure (18%). The
      simultaneous/sequential pattern did not significantly interact with estimator
      variables and no lineup-position effects were observed for either the
      simultaneous or sequential procedures. Rates of nonidentification were not
      significantly different for simultaneous and sequential but nonidentifiers from
      the sequential procedure were more likely to use the "not sure" response option
      than were nonidentifiers from the simultaneous procedure. Among witnesses who
      made an identification, 36% (41% of simultaneous and 32% of sequential)
      identified a known-innocent filler rather than a suspect, indicating that
      eyewitness performance overall was very poor. The results suggest that the
      sequential procedure that is used in the field reduces the identification of
      known-innocent fillers, but the differences are relatively small.

PMID- 24933176
TI  - Predictors of juveniles' noncompliance with probation requirements.
AB  - Probation is the most common disposition for adjudicated youth, but little is
      known about which specific requirements are commonly imposed on juveniles, the
      requirements with which juveniles most often fail to comply, and how certain
      youth characteristics and/or imposed requirements might relate to probation
      noncompliance. An investigation of 120 archived files of youth represented by an
      urban public defender's office identified 29 probation requirements imposed on
      youth and 18 requirements with which youth commonly failed to comply. Results
      revealed that 52% of youth failed to comply with at least one probation
      requirement; prior probation noncompliance and race were both significantly
      associated with noncompliance in the examined probation disposition. In addition,
      the probability of probation noncompliance was significantly higher when youth
      received either of two substance-related probation requirements: drug tests or
      drug and alcohol counseling. Such results may prompt further investigation of
      juvenile probation-related predictors, identify areas of need for clinical
      service provision to foster successful completion of probation requirements, and
      help identify areas of potential biases among juvenile court personnel.

PMID- 24933178
TI  - Visible light driven benzyl alcohol dehydrogenation in a dye-sensitized
      photoelectrosynthesis cell.
AB  - Light-driven dehydrogenation of benzyl alcohol (BnOH) to benzaldehyde and
      hydrogen has been shown to occur in a dye-sensitized photoelectrosynthesis cell
      (DSPEC). In the DSPEC, the photoanode consists of mesoporous films of TiO2
      nanoparticles or of core/shell nanoparticles with tin-doped In2O3 nanoparticle
      (nanoITO) cores and thin layers of TiO2 deposited by atomic layer deposition
      (nanoITO/TiO2). Metal oxide surfaces were coderivatized with both a ruthenium
      polypyridyl chromophore in excess and an oxidation catalyst. Chromophore
      excitation and electron injection were followed by cross-surface electron
      transfer activation of the catalyst to -Ru(IV)?O(2+), which then oxidizes benzyl
      alcohol to benzaldehyde. The injected electrons are transferred to a Pt electrode
      for H2 production. The nanoITO/TiO2 core/shell structure causes a decrease of up
      to 2 orders of magnitude in back electron-transfer rate compared to TiO2. At the
      optimized shell thickness, sustained absorbed photon to current efficiency of
      3.7% was achieved for BnOH dehydrogenation, an enhancement of ~10 compared to
      TiO2.

PMID- 24933177
TI  - Sumoylation regulates ER stress response by modulating calreticulin gene
      expression in XBP-1-dependent mode in Caenorhabditis elegans.
AB  - Excessive accumulation of unfolded proteins in the endoplasmic reticulum (ER)
      lumen causes ER stress, which induces a set of genes, including those encoding ER
      resident chaperones, to relieve the detrimental effects and recover homeostasis.
      Calreticulin is a chaperone that facilitates protein folding in the ER lumen, and
      its gene expression is induced by ER stress in Caenorhabditis elegans.
      Sumoylation conjugates small ubiquitin-like modifier (SUMO) proteins with target
      proteins to regulate a variety of biological processes, such as protein
      stability, nuclear transport, DNA binding, and gene expression. In this study, we
      showed that C. elegans X-box-binding protein 1 (Ce-XBP-1), an ER stress response
      transcription factor, interacts with the SUMO-conjugating enzyme UBC-9 and a
      SUMOylation target. Our results indicated that abolishing sumoylation enhanced
      calreticulin expression in an XBP-1-dependent manner, and the resulting increase
      in calreticulin counteracted ER stress. Furthermore, sumoylation was repressed in
      C. elegans undergoing ER stress. Finally, RNAi against ubc-9 mainly affected the
      expression of genes associated with ER functions, such as lipid and organic acid
      metabolism. Our results suggest that sumoylation plays a regulatory role in ER
      function by controlling the expression of genes required for ER homeostasis in C.
      elegans. 

PMID- 24933179
TI  - The synergetic effect of MoS2 and graphene on Ag3PO4 for its ultra-enhanced
      photocatalytic activity in phenol degradation under visible light.
AB  - The photo-degradation of organic pollutants using solar light is an attractive
      chemical process for water pollution control. In this study, we synthesized a new
      composite material consisting of silver phosphate (Ag3PO4) sub-microcrystals
      grown on a layered molybdenum disulfide (MoS2) and graphene (GR) hybrid as a high
      performance photocatalyst for the degradation of toxic organic pollutants. This
      composite photocatalyst was prepared via a simple two-step hydrothermal process
      that used sodium molybdate, thiourea and graphene oxide as precursors for the
      MoS2/GR hybrid and silver nitrate for the Ag3PO4 sub-microcrystals. The composite
      Ag3PO4-0.02(MoS2/0.005GR) was found to be the most effective catalyst for the
      photo-decomposition of 2,4-dichlorophenol under simulated solar light and visible
      light (lambda >= 420 nm). The photocatalyst was also highly active for the
      degradation of nitrophenol and chlorophenol. The ultra photocatalytic activity of
      the novel catalyst arose from the synergetic effects of MoS2 and GR as
      cocatalysts in the composite. MoS2/GR nanosheets served as electron collectors
      for the interfacial electron transfer from Ag3PO4 to electron acceptors in the
      aqueous solution and thus enhanced the separation of the photo-generated electron
      hole pairs and made the holes more available for organic oxidation. In addition,
      the presence of MoS2 and GR provided more active adsorption sites and allowed for
      the activation of dissolved O2 for organic degradation in water.

PMID- 24933180
TI  - Integrating laptops into an undergraduate nursing curriculum: implementation and
      evaluation.

PMID- 24933181
TI  - Amazing news for sharable/comparable nursing data to support big data science.

PMID- 24933183
TI  - Sunlight-driven photochemical halogenation of dissolved organic matter in
      seawater: a natural abiotic source of organobromine and organoiodine.
AB  - Reactions of dissolved organic matter (DOM) with photochemically generated
      reactive halogen species (RHS) may represent an important natural source of
      organohalogens within surface seawaters. However, investigation of such processes
      has been limited by difficulties in quantifying low dissolved organohalogen
      concentrations in the presence of background inorganic halides. In this work,
      sequential solid phase extraction (SPE) and silver-form cation exchange
      filtration were utilized to desalt and preconcentrate seawater DOM prior to
      nonspecific organohalogen analysis by ICP-MS. Using this approach, native
      organobromine and organoiodine contents were found to range from 3.2-6.4 * 10(-4)
      mol Br/mol C and 1.1-3.8 * 10(-4) mol I/mol C (or 19-160 nmol Br L(-1) and 6-36
      nmol I L(-1)) within a wide variety of natural seawater samples, compared with
      0.6-1.2 * 10(-4) mol Br/mol C and 0.6-1.1 * 10(-5) mol I/mol C in terrestrial
      natural organic matter (NOM) isolates. Together with a chemical probe method
      specific for RHS, the SPE+ICP-MS approach was also employed to demonstrate
      formation of nanomolar levels of organobromine and organoiodine during simulated
      and natural solar irradiation of DOM in artificial and natural seawaters. In a
      typical experiment, the organobromine content of 2.1 * 10(-4) mol C L(-1) (2.5 mg
      C L(-1)) of Suwannee River NOM in artificial seawater increased by 69% (from 5.9
      * 10(-5) to 1.0 * 10(-4) mol Br/mol C) during exposure to 24 h of simulated
      sunlight. Increasing I(-) concentrations (up to 2.0 * 10(-7) mol L(-1)) promoted
      increases of up to 460% in organoiodine content (from 8.5 * 10(-6) to 4.8 * 10(
      5) mol I/mol C) at the expense of organobromine formation under the same
      conditions. The results reported herein suggest that sunlight-driven reactions of
      RHS with DOM may play a significant role in marine bromine and iodine cycling. 

PMID- 24933184
TI  - Physiological changes in blood pressure impact peripheral endothelial function
      during adolescence.
AB  - Reactive hyperemia index is a measure of endothelial function used to assess
      subclinical atherosclerosis. When evaluated in healthy adolescents, significant
      changes in endothelial function were correlated with advancing age, pubertal
      status, and blood pressure. Blood pressure was the principal contributor to
      reactive hyperemia index variability independent of age, lipid profile, body mass
      index, and/or pubertal status. Interpretation of this peripheral vascular marker
      should include age and maturational changes in paediatric patients. 

PMID- 24933185
TI  - The role of nitric oxide in the object recognition memory.
AB  - The novel object recognition task (NORT) assesses recognition memory in animals.
      It is a non-rewarded paradigm that it is based on spontaneous exploratory
      behavior in rodents. This procedure is widely used for testing the effects of
      compounds on recognition memory. Recognition memory is a type of memory severely
      compromised in schizophrenic and Alzheimer's disease patients. Nitric oxide (NO)
      is sought to be an intra- and inter-cellular messenger in the central nervous
      system and its implication in learning and memory is well documented. Here I
      intended to critically review the role of NO-related compounds on different
      aspects of recognition memory. Current analysis shows that both NO donors and NO
      synthase (NOS) inhibitors are involved in object recognition memory and suggests
      that NO might be a promising target for cognition impairments. However, the
      potential neurotoxicity of NO would add a note of caution in this context. 

PMID- 24933186
TI  - Nitric oxide facilitates active avoidance learning via enhancement of glutamate
      levels in the hippocampal dentate gyrus.
AB  - The hippocampus is a key structure for learning and memory in mammals, and long
      term potentiation (LTP) is an important cellular mechanism responsible for
      learning and memory. Despite a number of studies indicating that nitric oxide
      (NO) is involved in the formation and maintenance of LTP as a retrograde
      messenger, few studies have used neurotransmitter release as a visual indicator
      in awake animals to explore the role of NO in learning-dependent long-term
      enhancement of synaptic efficiency. Therefore, in the present study, the effects
      of l-NMMA (a NO synthase inhibitor) and SNP (a NO donor) on extracellular
      glutamate (Glu) concentrations and amplitudes of field excitatory postsynaptic
      potential (fEPSP) were measured in the hippocampal dentate gyrus (DG) region
      during the acquisition and extinction of active-avoidance behavior in freely
      moving conscious rats. In the control group, the extracellular concentration of
      Glu in the DG was significantly increased during the acquisition of active
      avoidance behavior and gradually returned to baseline levels following extinction
      training. In the experimental group, the change in Glu concentration was
      significantly reduced by local microinjection of l-NMMA, as was the acquisition
      of the active-avoidance behavior. In contrast, the change in Glu concentration
      was significantly enhanced by SNP, and the acquisition of the active-avoidance
      behavior was significantly accelerated. Furthermore, in all groups, the changes
      in extracellular Glu were accompanied by corresponding changes in fEPSP amplitude
      and active-avoidance behavior. Our results suggest that NO in the hippocampal DG
      facilitates active avoidance learning via enhancements of glutamate levels and
      synaptic efficiency in rats. 

PMID- 24933187
TI  - Potential of a smartphone as a stress-free sensor of daily human behaviour.
AB  - Behaviour is one of the most powerful objective signals that connotes
      psychological functions regulated by neuronal network systems. This study
      searched for simple behaviours using smartphone sensors with three axes for
      measuring acceleration, angular speed and direction. We used quantitative
      analytic methodology of pattern recognition for work contexts, individual workers
      and seasonal effects in our own longitudinally recorded data. Our 13 laboratory
      members were involved in the care of common marmosets and domestic chicks, which
      lived in separate rooms. They attached a smartphone to their front waist-belts
      during feeding and cleaning in five care tasks. Behavioural characteristics such
      as speed, acceleration and azimuth, pitch, and roll angles were monitored.
      Afterwards, participants noted subjective scores of warmth sensation and work
      efficiency. The multivariate time series behavioral data were characterized by
      the subjective scores and environmental factors such as room temperature, season,
      and humidity, using the linear mixed model. In contrast to high-precision but
      stress-inducing sensors, the mobile sensors measuring daily behaviours allowed us
      to quantify the effects of the psychological states and environmental factors on
      the behavioural traits. 

PMID- 24933188
TI  - Clozapine and glycinamide prevent MK-801-induced deficits in the novel object
      recognition (NOR) test in the domestic rabbit (Oryctolagus cuniculus).
AB  - Studies in humans indicate that acute administration of sub-anesthetic doses of
      ketamine, an NMDA receptor antagonist, provokes schizophrenic-like symptoms in
      healthy volunteers, and exacerbates existing symptoms in individuals with
      schizophrenia. These and other findings suggest that NMDA receptor hypofunction
      might participate in the pathophysiology of schizophrenia, and have prompted the
      development of rodent pharmacological models for this disorder based on acute or
      subchronic treatment with NMDA receptor antagonists, as well as the development
      of novel pharmacotherapies based on increasing extrasynaptic glycine
      concentrations. In the present study, we tested whether acute hyperlocomotory
      behavior and/or deficits in the novel object recognition (NOR) task, induced in
      male rabbits by the acute subcutaneous (s.c.) administration of MK-801 (0.025 and
      0.037 mg/kg s.c., respectively), were prevented by prior administration of the
      atypcial antipsychotic, clozapine (0.2mg/kg, s.c.), or the glycine pro-drug
      glycinamide (56 mg/kg, s.c.). We found that clozapine fully prevented the MK-801
      induced hyperlocomotion, and both clozapine and glycinamide prevented MK-801
      induced deficits in the NOR task. The present results show that MK-801-induced
      hyperlocomotion and deficits in the NOR task in the domestic rabbit demonstrate
      predictive validity as an alternative animal model for symptoms of schizophrenia.
      Moreover, these results indicate that glycinamide should be investigated in pre
      clinical models of neuropsychiatric disorders such as schizophrenia, obsessive
      compulsive disorder and anxiety disorders, where augmentation of extrasynaptic
      glycine concentrations may have therapeutic utility.

PMID- 24933189
TI  - A behavioral and micro positron emission tomography imaging study in a rat model
      of hypothyroidism.
AB  - Hypothyroidism leads to somatic, neuropsychological, and psychiatric changes that
      are similar to depression. The mechanisms underlying the behavioral abnormalities
      in adult onset hypothyroidism remain ambiguous. Hypothyroidism was induced in
      adult male Wistar rats by the maintenance of 0.05% propylthiouracil (PTU) in
      drinking water for 5 weeks (hypothyroid group; HP group); control rats (CON
      group) received an equivalent amount of water. The open field and sucrose
      preference tests were employed, and the link between behavioral changes and brain
      glucose metabolism was evaluated using micro positron emission tomography
      imaging. The open field test revealed slightly decreased locomotor activity and
      significantly reduced rearing and defecation in the hypothyroid group.
      Hypothyroid rats were also characterized by decreased body weight, sucrose
      preference, and relative sucrose intake compared to control rats. Hypothyroidism
      induced reduced brain glucose metabolism in the bilateral motor cortex, the
      caudate putamen, the cortex cingulate, the nucleus accumbens, and the frontal
      association cortex. A decreased sucrose preference was positively correlated with
      metabolic glucose changes in the caudate putamen and the nucleus accumbens. The
      results indicate that the activity pattern in adult onset hypothyroidism is
      different from the activity pattern when hypothyroidism is induced in the
      developmental period of the central nervous system. Decreased sucrose preference
      in hypothyroid rats may be attributed to anhedonia. Furthermore, these findings
      suggest there may be a common mechanism underlying adult onset hypothyroidism and
      depression. 

PMID- 24933190
TI  - CRF family peptides are differently altered by acute restraint stress and chronic
      unpredictable stress.
AB  - Corticotropin-releasing factor (CRF) acts to promote stress-like physiological
      and behavioral responses and is mainly expressed in the paraventricular
      hypothalamic nucleus (PVN). Urocortin 1 (Ucn1) is also a ligand to CRF type 1 and
      2 receptors that has been associated with the stress response. Ucn1 neurons are
      primarily found in the Edinger-Westphal (EW) nucleus. It has been previously
      proposed that CRF and Ucn1 differently modulate stress responses to distinct
      types of stressors. The present study used male Wistar rats to compare the
      effects of acute restraint stress and unpredictable chronic stress (UCS) through
      Fos-immunoreactivity (Fos-ir) on CRF-containing neurons of PVN and Ucn1
      containing EW centrally projecting neurons. Results showed that PVN neurons
      responded to both acute restraint and UCS. Also for the PVN, unspecific
      variables, dependent on the time animals remained in the laboratory, do not seem
      to alter Fos-ir, since no significant differences between acute and chronic
      control groups were found. On the other hand, EW neurons were only activated in
      response to acute restraint stress. Also, for this nucleus a significant
      difference was found between acute and chronic control groups, suggesting that
      unspecific variables, dependent on the time animals remain in the laboratory,
      interfere with the nucleus activation. These results suggest that CRF/Ucn1
      neuronal circuits encompass two interconnected systems, which are coordinated to
      respond to acute stressors, but are differentially activated during chronic
      unpredictable stress. 

PMID- 24933192
TI  - Intracardiac thrombus in children: the fine equilibrium between the risk and the
      benefit.
AB  - The medical records of 16 patients diagnosed as intracardiac thrombus were
      searched. The size, location and outcome of thrombus together with demographic
      data of patients were assessed. The median age of the patients was 2.2 years. Six
      patients were newborn and two patients were infant. The median size of thrombus
      was 9 mm. The localization was right atrium in seven, right ventricle in five,
      left ventricle in one, pulmonary artery in one, and superior vena cava in two
      patients. There was prematurity in five, ciyanotic congenital heart disease in
      one, blood culture positivity in three, malignancy in four, nephrotic syndrome in
      one, indwelling catheters in 10, and acquired or genetic thrombophilia in six
      patients as risk factors. In the treatment, the first choice was tissue
      plasminogen activator in two patients, heparin infusion in one patient and low
      molecular weight heparin in remaining 12 patients. In nine patients, therapy
      included parenteral antimicrobials together with anticoagulants. The result was
      complete resolution in 15 patients and in one patient thrombus was surgically
      removed. The median time was 16 (2-70) days for 50% resolution and 26 (3-93) days
      for complete resolution. There was a statistically significant (P = .027 and r =
      0.5) correlation between the size and the complete resolution time. There was no
      anticoagulant therapy related major complication. In patients with intracardiac
      thrombus, selection of anticoagulant therapy may decrease the risk of
      complications. Surgery is rarely required and thrombolytics are not usually
      necessary for resolution of thrombus.

PMID- 24933191
TI  - Experimenter effects on behavioral test scores of eight inbred mouse strains
      under the influence of ethanol.
AB  - Eight standard inbred mouse strains were evaluated for ethanol effects on a
      refined battery of behavioral tests in a study that was originally designed to
      assess the influence of rat odors in the colony on mouse behaviors. As part of
      the design of the study, two experimenters conducted the tests, and the study was
      carefully balanced so that equal numbers of mice in all groups and times of day
      were tested by each experimenter. A defect in airflow in the facility compromised
      the odor manipulation, and in fact the different odor exposure groups did not
      differ in their behaviors. The two experimenters, however, obtained markedly
      different results for three of the tests. Certain of the experimenter effects
      arose from the way they judged behaviors that were not automated and had to be
      rated by the experimenter, such as slips on the balance beam. Others were not
      evident prior to ethanol injection but had a major influence after the injection.
      For several measures, the experimenter effects were notably different for
      different inbred strains. Methods to evaluate and reduce the impact of
      experimenter effects in future research are discussed. 

PMID- 24933193
TI  - The association between apelin-12 levels and paroxysmal supraventricular
      tachycardia.
AB  - AIMS: Our aim was to investigate the apelin-12 levels in patients with
      atrioventricular tachyarrhythmias and compare with those in patients with lone
      atrial fibrillation. METHODS: Forty four patients with supraventricular
      tachycardia as atrial fibrillation, 44 patients with paroxysmal supraventricular
      tachycardia (P-SVT) as atrioventricular tachyarrhythmias, including
      atrioventricular nodal reentrant tachycardia or atrioventricular reentrant
      tachycardia, and 30 age- and sex-matched healthy individuals were included in the
      study. RESULTS: The apelin-12 levels were significantly lower in both atrial
      fibrillation and P-SVT groups than control group. In post-hoc analysis, there was
      no significant difference in apelin-12 levels between atrial fibrillation and P
      SVT groups (P = 0.9). Patients in atrial fibrillation group and patients in P-SVT
      group had significantly lower apelin-12 levels than control group, separately (P
      < 0.001 and P < 0.001, respectively). The sensitivity and specificity values of
      the apelin-12 levels for predicting SVT, including both atrial fibrillation and
      atrioventricular reentrant tachycardia or atrioventricular nodal reentrant
      tachycardia were 64.77 and 90%, respectively (cut-off value was 0.87). The area
      under the receiver operator characteristic curve was 0.834 for the apelin-12
      levels (P = 0.0001). CONCLUSION: Apelin-12 levels are lower in patients with
      atrial fibrillation and P-SVT than control groups. Lower apelin levels in
      patients with atrial fibrillation and P-SVT would be expected to result in a
      decrease in the conduction velocity.

PMID- 24933194
TI  - Myocardial biomarkers and delayed enhanced cardiac magnetic resonance
      relationship in clinically suspected myocarditis and insight on clinical outcome.
AB  - AIMS: The relationship of cardiac magnetic resonance (CMR) late gadolinium
      enhancement (LGE) with myocardial biomarkers and markers of inflammation in acute
      viral myocarditis is not clearly defined. We assessed the relationship of LGE
      with myocardial and inflammatory biomarkers measured during the acute phase of
      myocarditis and their predictive value on clinical outcome. METHODS: Patients
      with first clinical episode of acute viral myocarditis and complete CMR study,
      including cine and LGE images, were included. The peak values of troponin I,
      creatine kinase, C-reactive protein value at admission and LGE extent were
      reported for each case. A 29-month clinical follow-up was performed, and cardiac
      symptoms and adverse cardiac events (all-cause death, heart transplant,
      hospitalization for heart failure) were reported. RESULTS: Forty-one patients (39
      +/- 15 years and 78% men) were included. Median LGE extent was 13% [interquartile
      range (IQR) (9%, 19%)] of left-ventricular mass and mean left-ventricular
      ejection fraction was 56 +/- 11%. There was a significant correlation between
      peak troponin I and LGE extent (r = 0.51, P < 0.001), and between peak creatine
      kinase and LGE extent (r = 0.66, P < 0.001). There was no correlation between C
      reactive protein at admission and LGE extent (r = 0.27, P = 0.09). At follow-up,
      eight (20%) patients had an adverse clinical event. LGE extent was significantly
      associated with a worse New York Heart Association status at follow-up [odds
      ratio (OR) 1.21, 95% confidence interval (CI) 1.07, 1.37, P = 0.002]. After
      adjustment for left-ventricular ejection fraction, age and clinical presentation
      category, LGE extent remained an independent predictor of cardiovascular events
      (hazard ratio 1.42; 95% CI 1.05, 1.95, P = 0.027). CONCLUSIONS: LGE extent on CMR
      studies is significantly correlated to biomarkers of myocardial injury in
      patients with acute viral myocarditis, and is a significant independent predictor
      of adverse cardiovascular outcome.

PMID- 24933195
TI  - The roles of nitric oxide and hydrogen sulfide in the anti-atherosclerotic effect
      of atorvastatin.
AB  - AIMS: To investigate antiatherosclerosis effect of atorvastatin (ATV) in a rat
      atherosclerosis model, and to explore roles of nitric oxide and hydrogen sulfide
      (H2S) in this event. METHODS: After being fed a high-fat diet, the rats were
      treated with ATV, ATV combined with cystathionine-gamma-lyase (CSE) inhibitor DL
      propargylglycine, and ATV combined with endothelial nitric oxide synthase (eNOS)
      inhibitor N'-nitro-L-arginine-methyl ester hydrochloride from 9 to 12 weeks,
      respectively. At the end of the experiment, the animals were sacrificed.
      Pathologic changes of aortic arch were observed to assay the degree of
      atherosclerotic lesions. Serum total cholesterol (TC), triglyceride, low-density
      lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were
      determined. Further, nitric oxide, total nitric oxide synthase and eNOS, and H2S
      and CSE were also measured. RESULTS: Compared with the normal control group,
      serum TC, triglyceride, and LDL-C levels in the model group were significantly
      elevated (P < 0.05). Pathological result suggested typical atherosclerotic
      lesions after the high-fat diet. The serum nitric oxide, eNOS, H2S, and CSE
      significantly decreased (P < 0.05). Quantitative reverse transcription polymerase
      chain reaction (qRT-PCR) showed that mRNA levels of eNOS and CSE in the aortic
      arch of the model rats were significantly downregulated (P < 0.05). Actually, ATV
      significantly ameliorated atherosclerotic lesions. ATV also significantly
      downregulated increased serum TC and LDL-C, and upregulated decreased serum
      nitric oxide and eNOS. However, it had no significant effects on serum H2S and
      CSE (P > 0.05). ATV combined with DL-propargylglycine significantly reduced serum
      H2S and CSE, and increased serum nitric oxide and eNOS as compared to single ATV
      treatment (P < 0.05). ATV combined with N'-nitro-L-arginine-methyl ester
      hydrochloride significantly increased serum TC, LDL-C, H2S, and CSE, and
      decreased nitric oxide and eNOS as compared to the single ATV (P < 0.05).
      CONCLUSIONS: ATV significantly ameliorates atherosclerotic lesions and enhances
      the activity of serum nitric oxide system, but not H2S system. The blockage of
      nitric oxide pathway, but not H2S pathway, significantly weakens
      antiatherosclerosis of ATV.

PMID- 24933196
TI  - Separation of mediastinal shed blood during aortic valve surgery elicits a
      reduced inflammatory response.
AB  - AIMS: The detrimental effects of inflammation following cardiopulmonary bypass
      (CPB) could negatively affect the postoperative outcome in a specific subset of
      high-risk patients. We therefore investigated the impact of a CPB circuit
      (Admiral, Eurosets, Italy) that allows separation of intracavitary and
      mediastinal blood on the release of biochemical markers and clinical outcome when
      compared with a conventional circuit. METHODS: Thirty patients undergoing aortic
      valve surgery were prospectively enrolled and assigned to Admiral group (Group 1,
      G1, n = 15) or conventional CPB group (Group 2, G2, n = 15). The Admiral
      oxygenator allows for a separate collection of mediastinal blood processed
      through a cell-saver before retransfusion. Clinical data and biochemical
      parameters were measured preoperatively, during CPB and at different time-points
      postoperatively. RESULTS: Preoperative demographics, intraoperative data (as CPB
      and aortic cross-clamping time) and perioperative complications did not differ
      between groups. Inflammatory response was significantly decreased in G1, as
      assessed by means of D-dimer (G1 = 1332.3  +/-  953.9 vs. G2 = 2791.9  +/- 
      1740.7  ng/ml, P = 0.02), C-reactive protein (G1 = 169.1  +/-  164.8 vs. G2 =
      57.1  +/-  39.3  mg/l, P = 0.04), interleukin-6 (G1 = 11.8  +/- 12.5 vs. G2 =
      26.5  +/-  24.9  pg/ml, P = 0.02) and tumour necrosis factor-alpha (G1 = 29  +/- 
      28.7 vs. G2 = 45.5  +/-  23.6 pg/ml, P = 0.03). CONCLUSION: Although no
      considerable difference was detected in terms of perioperative outcomes, the
      Admiral oxygenator did result in a significant reduction of inflammatory markers
      during the early postoperative course.

PMID- 24933197
TI  - Treating cardiac myxomas: a 16-year Chinese single-center study.
AB  - AIMS: Currently, myxoma is the most common type of primary cardiac tumor
      diagnosed. This article describes the experience over the past 16 years with
      cases of cardiac myxoma in Chinese patients and elucidated the differences
      between solid and papillary myxomas. METHODS: The clinical details of 68 patients
      with cardiac myxomas who underwent surgery between January 1996 and January 2012
      at our center were retrospectively analyzed. RESULTS: The left atrium was the
      primary tumor site in 88% of the patients included in this study. The most common
      implant site was the interatrial septum (69%), especially for patients with solid
      tumors. Common clinical symptoms included dyspnea and palpitation, whereas
      embolic events occurred in 12 patients. Myxoma resection involved a midline
      sternotomy utilizing cardiopulmonary bypass. According to pathological
      classification, solid myxomas were present in 28 patients (47%), whereas
      papillary myxomas were detected in 40 patients (53%). In the solid group,
      arrhythmias and a larger tumor volume were more common. Correspondingly, in 97.4 
      +/-  2.5% of cases, secondary surgery was not needed after 10 years. Overall, the
      actuarial survival for patients undergoing surgical excision of myxoma was 98.4 
      +/-  1.6% at 5 years and 96.0  +/-  2.8% at 10 years. CONCLUSION: Solid myxomas
      were associated with more arrhythmias, a larger tumor volume, implantation in the
      interatrial septum, and a need for concomitant surgery compared with papillary
      myxomas. Further studies should determine whether serum or histological markers
      could be routinely used in combination with echocardiograms, MRI and computed
      tomography for the predictions of recurrent myxomas during annual follow-up
      examinations.

PMID- 24933198
TI  - Adipokines and endothelial dysfunction in acute myocardial infarction and the
      risk of recurrent cardiovascular events.
AB  - AIMS: The aim of the study was to evaluate the prognostic role of adipokines
      (adiponectin, apelin, resistin, and visfatin) in patients with acute myocardial
      infarction (AMI) in relation to the extent of glucose metabolism impairment and
      intensity of systemic low-grade inflammation. METHODS: This case-control study
      covered 131 patients with coronary artery disease: 104 consecutive patients with
      AMI (74% men, mean age of 62 +/- 11 years) treated with primary percutaneous
      coronary intervention with stent implantation, and 27 patients with stable angina
      (70% men, mean age of 63 +/- 11 years), who were initially assessed in terms of
      adipokine levels, C-reactive protein and various echocardiographic and vascular
      parameters. Major adverse cardiovascular events were recorded in the AMI group
      during 3-year follow-up. RESULTS: Resistin and visfatin serum levels were
      significantly higher (P < 0.001), and adiponectin and apelin were lower (P <
      0.001) in AMI patients as compared to patients with stable angina. In AMI
      patients, adipokine levels were not related to glucose metabolism disturbances,
      yet adiponectin (P = 0.03) and resistin (P = 0.001) concentrations were related
      to the number of affected coronary vessels. Serum adiponectin level correlated
      negatively (r = -0.608, P < 0.05), whereas resistin and visfatin correlated
      positively (r = 0.526, P < 0.05 and r = 0.352, P < 0.05, respectively) with C
      reactive protein levels. All of the analyzed adipokines significantly accounted
      for the flow-mediated dilation variability (Radjusted 32%) in the AMI group. The
      Cox survival analysis indicated that resistin and visfatin were independent risk
      factors of recurrent AMI/unstable angina, with the diagnostic threshold above
      12.2 ng/ml for resistin and above 11.8 ng/ml for visfatin concentrations.
      CONCLUSION: An abnormal profile in serum adipokines observed in AMI is related to
      systemic inflammation and the degree of atherosclerosis independently of glucose
      metabolism disturbances and heralds major adverse cardiovascular event occurrence
      in long-term observation.

PMID- 24933199
TI  - Changed outcomes of fetuses with congenital heart disease: new Italian
      Multicentre study.
AB  - OBJECTIVES: To analyse the outcomes of fetuses with congenital heart disease
      between 2000 and 2005 in comparison to a previous multicentre study regarding the
      period 1983-1996. PARTICIPANTS AND METHODS: Data of seven centres were
      prospectively collected, the inclusion criteria being a confirmed fetal diagnosis
      after birth or at autopsy and a known follow-up, for at least 6 months after
      birth. Data of 649 fetuses, median age at diagnosis 24 weeks' gestation (15-37),
      340/649 (52.4%) diagnosed before 24 weeks, were analysed. RESULTS: Sixty seven
      and 59 cases had chromosomal or extracardiac anomalies (10.3 and 9.1%).
      Termination of pregnancy was chosen in 21.6% of cases versus 28.9% in the
      previous study, being significantly lower in cases with early diagnosis (P
      <0.001). Out of 509 fetuses continuing pregnancy, 23 died in utero (4.5%) and 110
      (21.1%) postnatally, versus 43% in the previous study (P <0.0017). Total
      surgical/postprocedure death occurred in 20.6% (59/287 infants) versus 37%
      previously (P <0.003), 67 infants being premature and 35 with associated
      chromosomal or extracardiac anomalies. The current overall mortality rate was
      higher in cases with chromosomal or extracardiac anomalies (59.5 and 51.35%,
      respectively, whereas it was 20.1% in isolated congenital heart disease). Overall
      current survival was 376 of 509 (73.9%) versus 45% in the previous study (P
      <0.0001). CONCLUSION: Our data show a reduced overall and surgical mortality,
      with respect to our previous study, resulting from resulting from an improved
      perinatal management and treatment of affected fetuses in the more recent era.

PMID- 24933200
TI  - Glycated haemoglobin and long-term mortality in patients with ST Elevation
      Myocardial Infarction.
AB  - BACKGROUNDS/OBJECTIVES: We aimed at assessing the impact of increased HbA1c
      (>=6.5%) on 1-year mortality in consecutive patients with ST Elevation Myocardial
      Infarction (STEMI) submitted to primary percutaneous coronary intervention (PCI).
      METHODS: The study population comprises 1205 STEMI patients treated with primary
      PCI and consecutively admitted to our Center from 1 January 2004 to 31 December
      2011. RESULTS: Two hundred and seventy-six patients with previously diagnosed
      diabetes (276/1205, 22.9%, Group A), 78 patients without previously known
      diabetes and HbA1c at least 6.5% (78/1205, 6.5%, Group B) and 851 patients
      without previously known diabetes and HbA1c less than 6.5% (851/1205, 70.1%,
      Group C).At Cox regression analysis, HbA1c at least 6.5% was not related to 1
      year postdischarge mortality in patients with previously diagnosed diabetes nor
      in those without previously known diabetes.Kaplan-Meier survival curve analysis
      showed that patients in Group A exhibited the lowest survival rate, while
      patients in Group B (i.e. patients without previously known diabetes and with
      HbA1c >=6.5%) showed a significant reduction in their survival rate since 6
      months after discharge. CONCLUSION: In a large series of STEMI patients submitted
      to primary PCI, HbA1c levels were not related with outcomes at multivariable
      analysis.

PMID- 24933201
TI  - Orthostatic hypotension: definition, diagnosis and management.
AB  - Orthostatic hypotension commonly affects elderly patients and those suffering
      from diabetes mellitus and Parkinson's disease. It is a cause of significant
      morbidity in the affected patients. The goal of this review is to outline the
      pathophysiology, evaluation, and management of the patients suffering from
      orthostatic hypotension. 

PMID- 24933202
TI  - Mind injuries after cardiac surgery.
AB  - After cardiac surgery, delirium, cognitive dysfunction, depression, or anxiety
      disorders frequently occur, and profoundly affect patients' prognosis and quality
      of life. This narrative review focuses on the main clinical presentations of
      cognitive and psychological problems ('mind injuries') that occur postoperatively
      in absence of ascertainable focal neurologic deficits, exploring their
      pathophysiological mechanisms and possible strategies for prevention and
      treatment. Postoperative cognitive dysfunction is a potentially devastating
      complication that can involve several mechanisms and several predisposing,
      intraoperative, and postoperative risk factors, which can result in or be
      associated to cerebral microvascular damage. Postoperative depression is
      influenced by genetic or psychosocial predisposing factors, by neuroendocrine
      activation, and by the release of several pro-inflammatory factors. The net
      effect of these changes is neuroinflammation. These complex biochemical
      alterations, along with an aspecific response to stressful life events, might
      target the function of several brain areas, which are thought to represent a
      trigger factor for the onset of depression. 

PMID- 24933203
TI  - Right heart failure due to a fistula between a giant aortic pseudoaneurysm and
      the left atrium: a late complication after cardiovascular surgery.
AB  - : A 69-year-old woman, treated 5 years before with mechanical aortic valve and
      vascular prosthesis of ascending aorta implantation for severe aortic
      regurgitation and dilation of ascending aorta, was referred to our center for
      dyspnea and peripheral edema. The transthoracic echocardiography showed a giant
      pseudoaneurysm incorporating the vascular prosthesis and a fistula of it with the
      left atrium. These findings were confirmed using the transesophageal
      echocardiogram, cardiac computed tomography, and during cardiac surgery, which
      was performed 5 days later. The reparative intervention consisted of suturing of
      both the connections; the patient survived the surgery, but she died 6 weeks
      later due to infectious complications.

PMID- 24933204
TI  - The impact of the metabolic syndrome on the outcome after aortic valve
      replacement.
AB  - OBJECTIVES: The aim of this study was to examine the influence of the metabolic
      syndrome on the left ventricular geometry as well as on the early and mid-time
      outcome in patients with aortic stenosis who underwent aortic valve replacement.
      METHODOLOGY: The study included 182 patients who underwent aortic valve
      replacement due to aortic stenosis. The metabolic syndrome was defined by the
      presence of at least three AHA-NHLB (American Heart Association/National Heart,
      Lung and Blood Institute) criteria. All the patients were followed for at least 2
      years after the surgery. RESULTS: The metabolic syndrome did not influence the
      severity of aortic stenosis (mean gradient and aortic valve area). However, the
      metabolic syndrome was associated with the reduced prevalence of the normal left
      ventricular geometry and the increased risk of concentric left ventricular
      hypertrophy in patients with aortic stenosis. Among the metabolic syndrome
      criteria, only increased blood pressure was simultaneously associated with the
      short-term and mid-term outcome, independently of other risk factors. Increased
      fasting glucose level was an independent predictor of the only 30-day outcome
      after the valve replacement. The metabolic syndrome and left ventricular
      hypertrophy were, independently of hypertension and diabetes, associated with the
      30-day outcome, as well as incidence of major cerebrovascular and cardiovascular
      events in the 2-year postoperative period. CONCLUSION: The metabolic syndrome
      does not change severity of the aortic stenosis, but significantly impacts the
      left ventricular remodeling in these patients. The metabolic syndrome and left
      ventricular hypertrophy, irrespective of hypertension and diabetes, are
      predictors of the short-term and mid-term outcome of patients with aortic
      stenosis who underwent aortic valve replacement.

PMID- 24933205
TI  - Airflow reversibility and long-term outcomes in patients with COPD without
      comorbidities.
AB  - BACKGROUND: The forced expiratory volume at first second (FEV(1)) during
      spirometry reflects the severity of chronic obstructive pulmonary disease (COPD)
      and is known to be an important prognostic factor. It is uncertain whether the
      response to short-acting bronchodilators may predict long-term outcomes such as
      hospitalizations and mortality. METHODS: We retrospectively studied a total of
      1203 consecutive COPD patients without significant comorbidities during a mean
      (+/-SD) of 69 +/- 39 months of follow-up. At baseline the subjects were
      classified as those with positive or negative bronchodilator test (BDT) and also
      in quartiles of absolute bronchodilator response to 400 MUg of salbutamol.
      Hospital visits and mortality were the end points. RESULTS: A positive
      bronchodilator test was observed in 332 (27.6%) of the patients. There were 73
      (21.9%) deaths in patients with a positive BDT versus 253 (28.7%) in those with a
      negative BDT (p = 0.04). In adjusted Cox regression analysis a positive BDT was
      significantly associated with a prolonged time to first hospitalization. After
      stratifying the population by quartiles of response to BDT, a dose-response
      relationship was observed with the best outcomes in the quartile with highest
      level of airflow reversibility, even after controlling for age, sex, BMI, smoking
      status and baseline postbronchodilator FEV(1). CONCLUSIONS: In a large population
      of well characterized COPD patients without significant comorbidities, those
      demonstrating higher levels of reversibility at baseline presented better long
      term outcomes even after controlling for other known prognostic factors.

PMID- 24933206
TI  - Solute concentration-dependent contact angle hysteresis and evaporation stains.
AB  - The presence of nonvolatile solutes in a liquid drop on a solid surface can
      affect the wetting properties. Depending on the surface-activity of the solutes,
      the extent of contact angle hysteresis (CAH) can vary with their concentration
      and the pattern of the evaporation stain is altered accordingly. In this work,
      four types of concentration-dependent CAH and evaporation stains are identified
      for a water drop containing polymeric additives on polycarbonate. For polymers
      without surface-activity such as dextran, advancing and receding contact angles
      (thetaa and thetar) are independent of solute concentrations, and a concentrated
      stain is observed in the vicinity of the drop center after complete evaporation.
      For polymers with weak surface-activity such as poly(ethylene glycol) (PEG), both
      thetaa and thetar are decreased by solute addition, and the stain pattern varies
      with increasing PEG concentration, including a concentrated stain and a mountain
      like island. For polymers with intermediate surface-activity such as sodium
      polystyrenesulfonate (NaPSS), thetaa descends slightly, but thetar decreases
      significantly after the addition of a substantial amount of NaPSS, and a ring
      like stain pattern is observed. Moreover, the size of the ring stain can be
      controlled by NaPSS concentration. For polymers with strong surface-activity such
      as poly(vinylpyrrolidone) (PVP), thetaa remains essentially a constant, but
      thetar is significantly lowered after the addition of a small amount of PVP, and
      the typical ring-like stain is seen. 

PMID- 24933207
TI  - Plerixafor and G-CSF for autologous stem cell mobilization in AL amyloidosis.

PMID- 24933208
TI  - Clinical impact of pre-transplant diastolic function on outcome after allogeneic
      hematopoietic SCT.

PMID- 24933209
TI  - Essential requirements for setting up a stem cell processing laboratory.
AB  - The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow
      Transplantation wrote this guideline to assist physicians and laboratory
      technologists with the setting up of a cell processing laboratory (CPL) to
      support a hematopoietic stem cell transplant program, thereby facilitating the
      start-up of a transplant program in a new location and improving patient access
      to transplantation worldwide. This guideline describes the minimal essential
      features of designing such a laboratory and provides a list of equipment and
      supply needs and staffing recommendations. It describes the typical scope of
      services that a CPL is expected to perform, including product testing services,
      and discusses the basic principles behind the most frequent procedures. Quality
      management (QM) principles specific to a CPL are also discussed. References to
      additional guidance documents that are available worldwide to assist with QM and
      regulatory compliance are also provided.

PMID- 24933210
TI  - New frontiers in pediatric Allo-SCT: novel approaches for children and
      adolescents with ALL.
AB  - Although most children with ALL can be cured by chemotherapy approaches,
      allogeneic hematopoietic cell transplant (HCT) therapy offers a better chance of
      cure to selected high-risk patients in first remission and most children who
      relapse. Although transplant-related mortality has decreased significantly in the
      past decade, relapse remains high after HCT for ALL; developing strategies to
      decrease relapse and improve survival are vital. Recent studies have shown that
      relapse risk can be accurately defined using measurements of minimal residual
      disease (MRD) both pre- and post-HCT and by knowing whether patients get GVHD in
      the first 2 months after transplant. With these risk definitions in hand,
      investigators are now applying novel agents and immunotherapeutic methods in
      attempt to lower MRD before transplant and modulate the GVL effect after
      transplant. With powerful new immunological approaches coming on line, the
      transplant process itself will likely expand to include pre and/or post-HCT
      interventions aimed at reducing relapse. 

PMID- 24933212
TI  - Pitfalls in the use of randomised controlled trials for fish oil studies with
      cardiac patients.
AB  - Randomised controlled trials (RCT) examining the effects of fish oil
      supplementation on cardiac outcomes have yielded varying results over time.
      Although RCT are placed at the top of the evidence hierarchy, this methodology
      arose in the framework of pharmaceutical development. RCT with pharmaceuticals
      differ in important ways from RCT involving fish oil interventions. In
      particular, in pharmaceutical RCT, the test agent is present only in the
      intervention group and not in the control group, whereas in fish oil RCT, n-3
      fats are present in the diet and in the tissues of both groups. Also, early phase
      studies with pharmaceuticals determine pharmacokinetics and pharmacodynamics to
      design the dose of the RCT intervention so that it is in a predicted linear dose
      response range. None of this happens in fish oil RCT, and there is evidence that
      both baseline n-3 intake and tissue levels may be sufficiently high in the dose
      response range that it is not possible to demonstrate a clinical effect with a
      RCT. When these issues are considered, it is possible that the changing pattern
      of fish consumption and fish oil use over time, especially in cardiac patients,
      can explain the disparity where benefit was observed in the early fish oil trials
      but not in the more recent trials. 

PMID- 24933211
TI  - Notoginsenoside R1 attenuates atherosclerotic lesions in ApoE deficient mouse
      model.
AB  - AIMS: Atherosclerosis is the primary cause of cardiovascular diseases and stroke.
      The current study evaluated the interventional effects of a naturally occurring
      compound Notoginsenoside R1 (NR1) on atherosclerosis in ApoE-/- mice. METHODS AND
      RESULTS: The atherosclerotic lesion was significantly alleviated by NR1 treatment
      and this attenuation was marked by reduction in lipid deposition, fibrosis and
      oxidative stress. Increased serum levels of GSH and SOD and decreased level of
      MDH were observed in NR1-treated ApoE-/- mice. NR1 treatment also significantly
      decreased the levels of CHO, TG, ox-LDL and increased the level of HDL.
      Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF
      alpha and gamma-IFN were markedly reduced in NR1-treated ApoE-/- mice.
      Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR
      126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR
      92a were observed in the vehicle-treated ApoE-/- mice. While NR1 treatment led to
      a significant reduction in the expression of miR-21, miR-26a, miR-126 and
      increased expression of miR-20a. CONCLUSION: Collectively, our results
      demonstrated for the first time the anti-atherosclerotic effects of NR1, which
      could be in part mediated through its multiple targeting effects on inflammation,
      oxidative stress, lipid metabolism and microRNA expression. These results
      therefore justify further evaluation of NR1 as a therapeutic agent treating
      atherosclerosis.

PMID- 24933213
TI  - Exercise training decreases gene expression of endo- and xeno-sensors in rat
      small intestine.
AB  - The purpose of the study was to test the hypothesis that gene expression of
      members of the nuclear receptor (NR) superfamily known to act as endo- and xeno
      sensors is reduced in the ileum of exercise-trained (Tr) rats. Healthy female
      rats were either treadmill-trained for 8 weeks, 5 times/week, or remained
      sedentary (Sed). Training resulted in a significant (p < 0.05) decrease in plasma
      free fatty acid (0.18 +/- 0.01 to 0.15 +/- 0.01 mmol/L) and glycerol (24.8 +/-
      0.8 to 18.7 +/- 0.8 mg/L) concentrations. Gene expressions of NRs farnesoid X
      receptor (FXR; p < 0.05), liver X receptor (LXR; p < 0.05), pregnane X receptor
      (PXR; p < 0.01), and retinoid X receptor (RXR; p < 0.06) were reduced in the
      ileum of Tr compared with Sed animals. Tr was also associated with a reduction (p
      < 0.05) in gene expression of FXR downstream heterodimeric organite solute
      transporters alpha (OSTalpha) and beta (OSTbeta) involved in the transport of
      bile acids, LXR downstream genes heterodimeric ATP-binding cassette transporters
      (ABCG5/G8) involved in transport of absorbed cholesterol back to the lumen, and
      Niemann-Pick C1-like 1 (NPC1L1) involved in cholesterol absorption. These data
      indicate that exercise training lowers the expression of molecules involved in
      the defense system of the ileum against endobiotic and xenobiotic insults under
      normal conditions, thus, suggesting that regular exercise contributes to the
      intestinal maintenance of cholesterol and bile acid homeostasis. 

PMID- 24933214
TI  - Tracking functional status across the spinal cord injury lifespan: linking
      pediatric and adult patient-reported outcome scores.
AB  - OBJECTIVE: To use item response theory (IRT) methods to link scores from 2
      recently developed contemporary functional outcome measures, the adult Spinal
      Cord Injury-Functional Index (SCI-FI) and the Pedi SCI (both the parent version
      and the child version). DESIGN: Secondary data analysis of the physical
      functioning items of the adult SCI-FI and the Pedi SCI instruments. We used a
      nonequivalent group design with items common to both instruments and the Stocking
      Lord method for the linking. Linking was conducted so that the adult SCI-FI and
      Pedi SCI scaled scores could be compared. SETTING: Community. PARTICIPANTS: This
      study included a total sample of 1558 participants. Pedi SCI items were
      administered to a sample of children (n=381) with SCI aged 8 to 21 years, and of
      parents/caregivers (n=322) of children with SCI aged 4 to 21 years. Adult SCI-FI
      items were administered to a sample of adults (n=855) with SCI aged 18 to 92
      years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Five scales common
      to both instruments were included in the analysis: Wheelchair, Daily Routine/Self
      care, Daily Routine/Fine Motor, Ambulation, and General Mobility functioning.
      RESULTS: Confirmatory factor analysis and exploratory factor analysis results
      indicated that the 5 scales are unidimensional. A graded response model was used
      to calibrate the items. Misfitting items were identified and removed from the
      item banks. Items that function differently between the adult and child samples
      (ie, exhibit differential item functioning) were identified and removed from the
      common items used for linking. Domain scores from the Pedi SCI instruments were
      transformed onto the adult SCI-FI metric. CONCLUSIONS: This IRT linking allowed
      estimation of adult SCI-FI scale scores based on Pedi SCI scale scores and vice
      versa; therefore, it provides clinicians with a means of tracking long-term
      functional data for children with an SCI across their entire lifespan.

PMID- 24933216
TI  - School climate and bullying victimization: a latent class growth model analysis.
AB  - Researchers investigating school-level approaches for bullying prevention are
      beginning to discuss and target school climate as a construct that (a) may
      predict prevalence and (b) be an avenue for school-wide intervention efforts
      (i.e., increasing positive school climate). Although promising, research has not
      fully examined and established the social-ecological link between school climate
      factors and bullying/peer aggression. To address this gap, we examined the
      association between school climate factors and bullying victimization for 4,742
      students in Grades 3-12 across 3 school years in a large, very diverse urban
      school district using latent class growth modeling. Across 3 different models
      (elementary, secondary, and transition to middle school), a 3-class model was
      identified, which included students at high-risk for bullying victimization.
      Results indicated that, for all students, respect for diversity and student
      differences (e.g., racial diversity) predicted within-class decreases in reports
      of bullying. High-risk elementary students reported that adult support in school
      was a significant predictor of within-class reduction of bullying, and high-risk
      secondary students report peer support as a significant predictor of within-class
      reduction of bullying.

PMID- 24933215
TI  - Mapping the academic problem behaviors of adolescents with ADHD.
AB  - This study possessed 2 aims: (a) to develop and validate a clinician-friendly
      measure of academic problem behavior that is relevant to the assessment of
      adolescents with attention deficit/hyperactivity disorder (ADHD) and (b) to
      better understand the cross-situational expression of academic problem behaviors
      displayed by these youth. Within a sample of 324 adolescents with the Diagnostic
      and Statistical Manual of Mental Disorders, 4th Edition, Text Revision diagnosed
      ADHD (age M = 13.07, SD = 1.47), parent, teacher, and adolescent self-report
      versions of the Adolescent Academic Problems Checklist (AAPC) were administered
      and compared. Item prevalence rates, factorial validity, interrater agreement,
      internal consistency, and concurrent validity were evaluated. Findings indicated
      the value of the parent and teacher AAPC as a psychometrically valid measure of
      academic problems in adolescents with ADHD. Parents and teachers offered unique
      perspectives on the academic functioning of adolescents with ADHD, indicating the
      complementary roles of these informants in the assessment process. According to
      parent and teacher reports, adolescents with ADHD displayed problematic academic
      behaviors in multiple daily tasks, with time management and planning deficits
      appearing most pervasive. Adolescents with ADHD display heterogeneous academic
      problems that warrant detailed assessment prior to treatment. As a result, the
      AAPC may be a useful tool for clinicians and school staff conducting targeted
      assessments with these youth.

PMID- 24933217
TI  - Well-being, school climate, and the social identity process: a latent growth
      model study of bullying perpetration and peer victimization.
AB  - The present study concerns longitudinal research on bullying perpetration and
      peer victimization. A focus is on school factors of school climate (academic
      support, group support) and school identification (connectedness or belonging),
      which are conceptualized as related but distinct constructs. Analysis of change
      on these factors as well as individual well-being across time contributes to
      understanding bullying behavior. Latent growth modeling was employed to examine
      the predictors of anxiety, depression, 2 school climate factors and school
      identification in understanding change in physical and verbal bullying behavior.
      The sample included 492 Australian school students (means age 15 years, 53.5%
      male) in Grades 7 to 10 who completed measures over 3 years. Academic support and
      group support were the strongest predictors of change in bullying and
      victimization. Positive change in school identification also predicted a decrease
      in bullying behavior over time. An increase in depression or anxiety across time
      predicted an increase in rates of both bullying and victimization over time.
      Future research should continue to examine the complex relationship between
      individual-psychological and social-psychological variables in impacting on
      incidence of school-based bullying. On a practical note, school-based
      intervention programs may benefit from an approach that aims to target the school
      climate, social identity with the school, and promote individual psychological
      well-being.

PMID- 24933218
TI  - Understanding and measuring student engagement in school: the results of an
      international study from 12 countries.
AB  - The objective of the present study was to develop a scale that is appropriate for
      use internationally to measure affective, behavioral, and cognitive dimensions of
      student engagement. Psychometric properties of this scale were examined with data
      of 3,420 students (7th, 8th, and 9th grade) from 12 countries (Austria, Canada,
      China, Cyprus, Estonia, Greece, Malta, Portugal, Romania, South Korea, the United
      Kingdom, and the United States). The intraclass correlation of the full-scale
      scores of student engagement between countries revealed that it was appropriate
      to aggregate the data from the 12 countries for further analyses. Coefficient
      alphas revealed good internal consistency. Test-retest reliability coefficients
      were also acceptable. Confirmatory factor analyses indicated that the data fit
      well to a second-order model with affective, behavioral, and cognitive engagement
      as the first-order factors and student engagement as the second-order factor. The
      results support the use of this scale to measure student engagement as a
      metaconstruct. Furthermore, the significant correlations of the scale with
      instructional practices, teacher support, peer support, parent support, emotions,
      academic performance, and school conduct indicated good concurrent validity of
      the scale. Considerations and implications regarding the international use of
      this student engagement in school measure are discussed.

PMID- 24933219
TI  - Evaluation of toxicity of Calophyllum brasiliense stem bark extract by in vivo
      and in vitro assays.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Calophyllum brasiliense Camb., Clusiaceae, is
      commonly known as "guanandi" and its stem bark is used in Brazilian traditional
      medicine to treat rheumatism, vein problems, hemorrhoids and gastric ulcers. The
      aim of this study was to evaluate the toxicity of hexane extract of Calophyllum
      brasiliense stem bark (HECb) using in vitro and in vivo experimental models.
      MATERIALS AND METHODS: In vitro toxicity was evaluated by Alamar Blue
      cytotoxicity assay and micronucleus test, using Chinese hamster ovary (CHO-k1)
      epithelial cells. in vivo toxicity was evaluated by oral acute and subchronic
      toxicity assays. In the oral acute toxicity screening, a single dose of HECb was
      administered to mice at doses ranging from 250 to 1000 mg/kg. In the subchronic
      study, HECb was administered orally for 30 days to Wistar rats at doses of 100
      mg/kg and 500 mg/kg. Phytochemical analyses were performed by HPLC/UV-vis,
      secondary metabolites were quantified by spectrophotometric methods. RESULTS:
      HECb presented IC50=119.94+/-4.31 ug/mL after a 24 h cytotoxicity test using CHO
      k1 cells, showing low cytotoxicity. However, when the cells were exposed to HECb
      for 72 h, the IC50 value was 8.39+/-2.00 ug/mL, showing in this case, a
      pronounced cytotoxic effect. In the oral acute toxicity studies, doses up to 500
      mg/kg of HECb did not cause any changes in both male and female mice. At 1000
      mg/kg, male mice showed signs typical of depression and stimulation that were
      reversed at 72 h. Besides, female mice were more sensitive to the toxic effect of
      HECb at 1000 mg/kg, which initially presented typical agitation signals, followed
      by depression signals, leading to death of all the animals at 24h. In subchronic
      assay with rats, HECb administered orally at doses of 100 and 500 mg/kg did not
      cause significant changes in all clinical parameters evaluated. Histopathological
      analyses showed no deleterious effect in the vital organs of rats. Preliminary
      phytochemical analysis revealed the presence of phenolic compounds, steroids, and
      volatile coumarins. Analysis by HPLC showed two major peaks characteristic of
      chromanones. CONCLUSIONS: In vitro toxicological tests showed that HECb exhibited
      cytotoxicity especially after 72 h of exposition, and mutagenicity on the highest
      tested dose. The in vivo studies demonstrated that HECb produced some toxicity
      signs at the highest dose tested, particularly, in the acute toxicity test but
      showed no significant signs of toxicity in the subchronic assay. Based on these
      and previous pharmacological studies, it is possible to say that HECb did not
      exhibit significant toxicity at its effective dose. This suggests that HECb is
      relatively safe in humans at its effective dose.

PMID- 24933220
TI  - A survey on medicinal materials used in traditional systems of medicine in Sri
      Lanka.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sri Lanka has rich traditional systems of
      medicine, which cater to 60-70% of the rural population's primary health care
      needs. However, development of existing systems has been hindered by the
      unavailability of up-to-date information on medicinal materials and other related
      issues. For streamlining purposes, we investigated the present-day scenario of
      country's medicinal plant industry by gathering up-to-date information on the
      types of raw materials required, their aggregate quantities, heavily used and
      rare materials, family wise distribution, challenges faced by stakeholders as
      well as other pertinent issues. MATERIALS AND METHODS: The present survey covered
      the selected government Ayurveda hospitals, traditional and Ayurveda
      practitioners, large and small-scale herbal drug and cosmetic manufactures,
      importers, collectors and Ayurveda commissioners throughout the country. A
      systematic questionnaire was distributed and face-to-face interviews were
      conducted. Collected data were tabulated and analyzed. RESULTS: A diverse range
      of medicinal materials, including 290 species (64.73%) from dried plants, 59
      (13.17%) from fresh plants, 69 (15.40%) from minerals, 18 (4.02%) from animal
      sources and 12 (2.68%) from other sources were recorded. A total of 302 plant
      species belonging to 95 families, dominated by Leguminosae family, was listed.
      Out of these, 46 species belonging to 35 families were used intensively. A large
      portion of herbal materials was of completely local origin (71.13%) while 26%
      were imported and the rest (2.87%) can be obtained by both routes. Leaves were
      the most highly used part of the plant (22.2%). High price, poor quality,
      insufficient or totally absence of continuous supply and adulteration were the
      main constraints faced by the stakeholders. The unavailability of systematic
      cultivation and processing protocols, incorrect identification, and lack of
      proper quality control methodologies were identified as major challenges of the
      industry. CONCLUSION: The present study revealed a currently bleak scenario of
      the medicinal material industry in Sri Lanka. The results clearly demonstrated
      the need to implement a national strategy to address the major challenges faced
      by different stakeholders. Information generated through this study could be
      effectively incorporated for the formulation of a sustainable development
      strategy for this industry.

PMID- 24933221
TI  - Tongue diagnosis system for quantitative assessment of tongue coating in patients
      with functional dyspepsia: a clinical trial.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tongue diagnosis is a significant procedure to
      examine the physiological and pathological changes of the human body in oriental
      medicine. However, the conventional method of tongue diagnosis including direct
      observation of tongue has limitations because of various external factors and
      subjective factors. Therefore, the current study investigated the usefulness of
      the tongue diagnosis system (TDS) as a diagnostic tool for evaluating tongue
      coating thickness (TCT) by assessing the agreement between the TDS and a gold
      standard established by assessors using the conventional method. MATERIALS AND
      METHODS: The present study was designed as a prospective clinical trial including
      60 patients with functional dyspepsia. The TDS was used to capture tongue images
      twice within a 30-min interval to assess its reproducibility. Tongue coating
      percentage was measured by the TDS, and TCT was classified as either no coating,
      thin coating, or thick coating according to the existing diagnostic criteria.
      After both TDS examinations, the weight of tongue coating was quantitatively
      measured, and the correlation between the actual quantity of tongue coating and
      the percentage of the coating measured by the TDS was analyzed using Pearson's
      correlation. After collecting tongue images in all 60 patients, tongue coating
      was evaluated using a conventional method by 5 well-trained assessors to
      establish the gold standard for evaluating TCT, which allowed us to assess the
      diagnostic agreement between the TDS and the gold standard. After 2 weeks, TCT
      evaluation was repeated by the same assessors using the same images but in a
      random order. RESULTS: The agreement between the TDS and the gold standard for
      evaluating TCT was almost perfect (weighted kappa, 0.840), as was the
      reproducibility of the TDS (weighted kappa, 0.851). The percentage of tongue
      coating measured by the TDS was significantly correlated with the weight of
      tongue coating (r=0.442, p <0.001). The levels of intra-rater reliability ranged
      from substantial to almost perfect (range of weighted kappa, 0.777-0.923). The
      inter-rater reliability of 5 assessors was moderate (weighted kappa, 0.563).
      CONCLUSIONS: The present study demonstrated that the TDS can be used as a
      diagnostic tool for the objective and standardized evaluation of TCT in actual
      clinical practice.

PMID- 24933222
TI  - Complement activity of polysaccharides from three different plant parts of
      Terminalia macroptera extracted as healers do.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Water decoctions of the root bark, stem bark and
      leaves of Terminalia macroptera are used by traditional healers in Mali to cure a
      wide range of illnesses, such as wounds, hepatitis, malaria, fever, cough and
      diarrhea as well as tuberculosis. Plant polysaccharides isolated from crude water
      extracts have previously shown effects related to the immune system. The aims of
      this study are comparing the properties of the polysaccharides among different
      plant parts, as well as relationship between chemical characteristics and
      complement fixation activities when the plant material has been extracted as the
      traditional healers do, with boiling water directly. MATERIALS AND METHODS: Root
      bark, stem bark and leaves of Terminalia macroptera were extracted by boiling
      water, and five purified polysaccharide fractions were obtained by anion exchange
      chromatography and gel filtration. Chemical compositions were determined by GC of
      the TMS derivatives of the methyl-glycosides and the linkage determined after
      permethylation and GC-MS of the derived partly methylated alditol acetates. The
      bioactivity was determined by the complement fixation assay of the crude extracts
      and purified fractions. RESULTS: The acidic fraction TRBD-I-I isolated from the
      root bark was the most active of the fractions isolated. Structural studies
      showed that all purified fractions are of pectic nature, containing
      rhamnogalacturonan type I backbone. Arabinogalactan type II side chains were
      present in all fractions except TRBD-I-II. The observed differences in complement
      fixation activities among the five purified polysaccharide fractions are probably
      due to differences in monosaccharide compositions, linkage types and molecular
      sizes. CONCLUSION: The crude extracts from root bark and stem bark have similar
      total activities, both higher than those from leaves. The root bark, leaves and
      stem bark are all good sources for fractions containing bioactive
      polysaccharides. But due to sustainability, it is prefer to use leaves rather
      than the other two plant parts, and then the dosage by weight must be higher when
      using leaves.

PMID- 24933223
TI  - Sclederma of Poria cocos exerts its diuretic effect via suppression of renal
      aquaporin-2 expression in rats with chronic heart failure.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sclederma of Poria cocos (Hoelen) has been used
      as a diuretic in traditional Asian medicine. However, the underlying mechanism by
      which Sclederma of Poria cocos (hoelen) exerts its diuretic effect has not been
      well identified. The aim of the present study was to evaluate the effects of
      Sclederma of Poria cocos (hoelen) in rats with chronic heart failure (CHF)
      induced by acute myocardial infarction and to investigate the underlying
      mechanisms. MATERIALS AND METHODS: An aqueous extract of Sclederma of Poria cocos
      (hoelen) (2.4 g/kg/d, 1.2 g/kg/d or 0.6 g/kg/d) or furosemide (20 mg/kg/d) was
      administered orally to male Sprague-Dawley rats starting on the day of coronary
      ligation. The urine output of all rats was quantified and collected every day for
      1 or 4 weeks. The expression of aquaporin-2 (AQP2) was examined after treatment
      for 1 or 4 weeks. RESULTS: Urinary output increased significantly and urinary
      osmolality decreased after oral administration of Sclederma of Poria cocos
      (hoelen) for both 1 and 4 weeks. Sclederma of Poria cocos (hoelen) caused less
      electrolyte disorder than furosemide. Furthermore, Sclederma of Poria cocos
      (hoelen) reduced the levels of plasma BNP in CHF rats, whereas furosemide had no
      effect. Importantly, both mRNA and protein expression of AQP2 were down-regulated
      and urinary excretion of AQP2 was decreased after administration of Sclederma of
      Poria cocos (hoelen) to CHF rats. Similarly, Sclederma of Poria cocos (hoelen)
      reduced plasma arginine vasopressin (AVP) level and down-regulated vasopressin
      type 2 receptor (V2R) mRNA expression. CONCLUSIONS: Sclederma of Poria cocos
      (hoelen) exerts its diuretic effect and improves cardiac function in CHF rats via
      the AVP-V2R-AQP2 axis.

PMID- 24933224
TI  - Semen Astragali Complanati: an ethnopharmacological, phytochemical and
      pharmacological review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Semen Astragali Complanati (SAC), the dried ripe
      seed of Flatstem Milkvetch (Astragalus complanatus Bunge) (Leguminosae), is
      commonly used in traditional Chinese medicine (TCM) for treating muscle, liver,
      kidney, blood, skin and reproductive system diseases. MATERIALS AND METHODS:
      Relevant information about SAC was gathered via "Google Scholar", "ISI Web of
      Knowledge", "PubMed", "ScienceDirect", "Medline Plus", "ACS", "CNKI" and "Wiley
      Online Library" and from books in local libraries. RESULTS: The major contents of
      SAC include fatty acids, amino acids, polysaccharides, flavonoids, triterpene
      glycosides and trace elements. Previous scientific studies have reported that SAC
      exhibits a number of therapeutic effects on chronic diseases such as
      cardiovascular diseases, diabetes mellitus and cancers. It has been found that
      flavonoids are the main bioactive component in SAC. However most of the previous
      studies have shown the effects brought by the total flavonoid fraction extracted
      from SAC only; further studies are warranted for the biological effects produced
      by individual components. There are only a few studies on the toxicity of SAC and
      the overall results show that its toxicity is quite low or even non-existent.
      CONCLUSIONS: SAC is a valuable TCM herb with multiple pharmacological effects for
      treating some chronic diseases. More studies on SAC will help us to have a better
      understanding of its pharmacological mechanisms so as to provide more scientific
      evidence to explain its traditional uses, identify its therapeutic potential on
      other diseases and understand its possible harmful effects. Based on previous
      studies, it is easy to identify that antioxidant effect of SAC might play an
      important role on its pharmacological effects. Studying the effects of SAC on
      handling intracellular reactive oxygen species may be a potential direction to
      help understanding the molecular mechanisms of SAC on preventing and/or treating
      chronic diseases.

PMID- 24933225
TI  - Triptolide: progress on research in pharmacodynamics and toxicology.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f. (Tripterygium
      wilfordii), also known as Huangteng and gelsemium elegan, is a traditional
      Chinese medicine that has been marketed in China as Tripterygium wilfordii
      glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii
      extracts, has been used to treat various diseases, including lupus, cancer,
      rheumatoid arthritis and nephritic syndrome. This review summarizes recent
      developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy
      and toxicology of TP, with a focus on its novel mechanism of reducing toxicity.
      This review provides insight for future studies on traditional Chinese medicine,
      a field that is both historically and currently important. MATERIALS AND METHODS:
      We included studies published primarily within the last five years that were
      available in online academic databases (e.g., PubMed, Google Scholar, CNKI,
      SciFinder and Web of Science). RESULTS: TP has a long history of use in China
      because it displays multiple pharmacological activities, including anti
      rheumatism, anti-inflammatory, anti-tumor and neuroprotective properties. It has
      been widely used for the treatment of various diseases, such as rheumatoid
      arthritis, nephritic syndrome, lupus, Behcet's disease and central nervous system
      diseases. Recently, numerous breakthroughs have been made in our understanding of
      the pharmacological efficacy of TP. Although TP has been marketed as a
      traditional Chinese medicine, its multi-organ toxicity prevents it from being
      widely used in clinical practice. CONCLUSIONS: Triptolide, a biologically active
      natural product extracted from the root of Tripterygium wilfordii, has shown
      promising pharmacological effects, particularly as an anti-tumor agent.
      Currently, in anti-cancer research, more effort should be devoted to
      investigating effective anti-tumor targets and confirming the anti-tumor spectrum
      and clinical indications of novel anti-tumor pro-drugs. To apply TP
      appropriately, with high efficacy and low toxicity, the safety and non-toxic dose
      range for specific target organs and diseases should be determined, the altered
      pathways and mechanisms of exposure need to be clarified, and an early warning
      system for toxicity needs to be established. With further in-depth study of the
      efficacy and toxicity of TP, we believe that TP will become a promising multi-use
      drug with improved clinical efficacy and safety in the future.

PMID- 24933226
TI  - Dose-response of oridonin on hepatic cytochromes P450 mRNA expression and
      activities in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Oridonin, the major terpene found in Rabdosia
      rubescens, is widely used as a dietary supplement or therapeutic drug. The
      effects of oridonin on drug processing genes, such as cytochrome P450 and nuclear
      receptors, were still unclear. Therefore, the present study investigated the
      influence of oridonin on the hepatic drug metabolizing system to evaluate the
      safety through its drug interaction potential. MATERIALS AND METHODS: In this
      study, eight-week-old male C57BL/6 mice were treated oridonin orally (0, 25, 50,
      100, 200 mg/kg, i.g.) for 15 days. The effects of oridonin on major Cyps in mice
      livers were examined at both the mRNA and enzyme activity levels. RESULTS: In
      general, there are no significant influence of various dose of oridonin on mice
      liver function. However, oridonin significantly increased Cyps (1a, 2a, 2d, 2e,
      2c and 3a family) mRNA expression. In addition, it could induce Cyps activity in
      microsome incubation at maximum dosage. To our knowledge, it is the first time to
      identify oridonin as a Cyps inducer in vivo. It also promotes the expression of
      CAR, PXR and POR. CONCLUSION: These results indicate that, if studies in mice
      extrapolate to humans by orthologous genes, oridonin appears to be a risk to herb
      drug interactions due to its induction effects on drug processing genes
      expression and activation.

PMID- 24933227
TI  - The mechanism of hepatoprotective effect of sesquiterpene rich fraction from
      Cichorum glandulosum Boiss. et Huet on immune reaction-induced liver injury in
      mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cichorum glandulosum Boiss. et Huet is a
      traditional Uygur herbal medicine that has been used as a cholagogic and diuretic
      agent to improve liver function. However, the mechanism is not known for the
      liver-protective function. We investigated the antioxidant effects of plant
      extraction (CGE60) in vitro and in vivo, and find the mechanism of liver
      protection in Bacille Calmette-Guerin vaccine (BCG)+Lipopolysaccharides (LPS)
      induced liver injury in mice. MATERIALS AND METHODS: CGE60 was made, and the
      antioxidant activity was investigated by comparing the ability of scavenging 1,1
      diphenyl-2-picrylhydrazyl (DPPH), and 2,2-azinobis(3-ehtylbenzothiazolin-6
      sulfnicAcid) diammonium salt (ABTS) free radicals in vitro. Then, CGE60 was
      administrated in mice of liver damage model which was induced in mice using the
      BCG+LPS protocol. The CGE 60 extract was tested at three dosages: 50 mg/kg, 100
      mg/kg, and 200 mg/kg. Product of lipid peroxidation (MDA), superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GSH-PX,), nitric oxide (NO),
      nitric oxide synthetase (NOS), hydroxyproline and alkaline phosphatase (ALP)
      contents were evaluated in liver to determine the CGE60 activity in the hepatic
      injury model. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and
      transforming growth factor-beta (TGF-beta) proteins were determined in the liver
      tissues using ELSIA. The signaling activities were evaluated in Western blot.
      RESULTS: CGE60 exhibited strong antioxidant ability in vitro. With oral
      administration, CGE60 significantly increased the activity of CAT, SOD, GSH-PX,
      and decreased the level of NO, NO synthase, hydroxyproline, ALP and lipid
      peroxidation liver of in the BDG+ LPS model. CGE60 attenuated hepatic
      inflammation via down- regulation of TNF-alpha, IL-6 and TGF-beta. CGE60 blocked
      protein expression of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa-B (NF
      kappaB), phosphorylation of extracellular signal-regulated kinase (p-ERK1/2), and
      cyclooxygenase-2 (COX-2),but activated the expression of p-P38 MAPK. CONCLUSION:
      This study suggests that CGE60 possesses antioxidant activity and this activity
      associates with hepatoprotective effect in the mice of BCG +LPS model, and the
      mechanisms underlying these effects may involve antioxidant actions and anti
      inflammation activities.

PMID- 24933228
TI  - Toxicological evaluation of the hydroethanolic extract of Dilodendron bipinnatum
      Radlk.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dilodendron bipinnatum Radlk., Sapindaceae, is
      popularly known as 'mulher-pobre'. Its stem bark macerate or decoction is
      popularly used mainly to treat uterine inflammation and bone fractures. Acute
      oral and subchronic toxicities of the hydroethanolic extract of Dilodendron
      bipinnatum (HEDb) were investigated as well as the classes of phytochemical
      present in the extract. MATERIALS AND METHODS: Acute toxicity of HEDb was
      investigated by hippocratic screening in Swiss mice, cytotoxicity and potential
      genotoxic effect were evaluated with micronucleus test in the CHO-k1cells.
      Subchronic oral toxicity of HEDb was assessed in Wistar rats with graded doses of
      HEDb repeatedly administered for 30 days, in order to evaluate the behavioral
      changes, weight gain, water and feed consumption, urine and feces excretion,
      hematological and biochemical parameters and histopathological examinations of
      vital organs. RESULTS: In hippocratic screening doses up to 5000 mg/kg p.o. did
      not cause any changes in female mice, while signs of reduction in motility,
      increased respiratory rate and tail erection were observed in male mice but were
      all reversed within an hour. In cytotoxicity assay, IC50 was 118+/-1.55 ug/mL in
      CHO-k1 cells. Micronucleus test demonstrated that the plant extract is non
      genotoxic. In subchronic toxicity studies, minor change was observed as an
      increase in the urine output in the last 18 days of treatment with 500 mg/kg of
      HEDb, while other parameters remained unchanged. All alterations observed were
      discrete and minor in nature and were not accompanied by any relevant clinical
      signs or any toxicologically significant biochemical, hematological and
      histopathological changes. Preliminary phytochemical analysis revealed the
      presence of aurones, chalcones, coumarins, flavonones, flavononoids, phenols, and
      saponins. CONCLUSION: The results demonstrate high safety profile of HEDb in both
      experimental animals and cell models assays. However, there may be risk of
      hepatotoxicity in the use of the extract at high doses for a prolonged period.

PMID- 24933229
TI  - Resins-based denture soft lining materials modified by chlorhexidine salt
      incorporation: an in vitro analysis of antifungal activity, drug release and
      hardness.
AB  - OBJECTIVES: To evaluate the in vitro growth inhibition of Candida albicans, the
      rate of chlorhexidine release and shore A hardness from resins-based denture soft
      lining materials modified by chlorhexidine diacetate (CDA) or chlorhexidine
      hydrochloride (CHC) incorporation. METHODS: Resin discs were prepared from soft
      denture liners based on poly (methyl methacrylate) (PMMA) or poly (ethyl
      methacrylate) (PEMA) containing 0.5, 1.0 and 2.0 wt.% of CDA or CHC. For
      antifungal activity resin discs were placed on agar plates inoculated with C.
      albicans, after 48 h at 37 degrees C the diameters of inhibition zones were
      measured. For the chlorhexidine release, discs were immersed into distilled water
      at 37 degrees C, and spectral measurements were made after 48 h. Shore A hardness
      was evaluated at the baseline, 2 and 7 days, using 6mm thick rectangular
      specimens also immersed into distilled water at 37 degrees C. Data were
      statistically processed by SigmaStat software using ANOVA and all pairwise
      multiple comparison procedures was done using the Holm-Sidak method, with
      alpha=0.05 (p<0.001). RESULTS: CDA added to PMMA soft liner and PEMA soft liner
      had a dose-related inhibitory effect on C. albicans and on chlorhexidine release
      rate (p<0.001). The PMMA and PEMA hardness increased statistically by time but
      not for the different CDA concentrations. CHC had no inhibitory effect on C.
      albicans. SIGNIFICANCE: Chlorhexidine diacetate released from resins-based soft
      lining materials can be convenient to reduce the biofilm development on the
      material surface and treat denture stomatitis, without depending on patient
      compliance.

PMID- 24933230
TI  - Full-arch prostheses from translucent zirconia: accuracy of fit.
AB  - OBJECTIVES: The aim of this study was to evaluate the marginal and internal fit
      of single crowns, compared to 14-unit frameworks made of translucent yttria
      stabilized zirconia. We hypothesized that there is an influence of the type of
      restoration on the marginal and internal fit. METHODS: Eight teeth (FDI locations
      17, 15, 13, 11, 21, 23, 25 and 27) of a typodont maxillary model were provided
      with a chamfer preparation to accommodate a 14-unit prosthesis or four single
      crowns (SCs). Ten 14-unit fixed dental prostheses (FDPs) and 40 single crowns
      were fabricated using a computer aided design (CAD)/computer aided manufacturing
      (CAM) system with pre-sintered translucent yttria-stabilized zirconia blanks. The
      restorations were cemented onto twenty master dies, which were sectioned into
      four pieces each. Then, the marginal and internal fits were examined using a
      binocular microscope. In order to detect the differences between the two types of
      restorations a non-parameteric test (Mann-Whitney-U) was carried out; to detect
      differences between the abutment teeth and the abutment surfaces non-parametric
      tests (Kruskal-Wallis) and pairwise post hoc analyses (Mann-Whitney-U) were
      performed after testing data for normal distribution (method according to Shapiro
      Wilk). Level of significance was set at 5%. RESULTS: The mean (SD) marginal
      opening gap dimensions were 18 MUm (14) for the single crowns and 29 MUm (27) for
      the 14-unit FDPs (p<0.001). Abutment 21 of the FDPs showed statistical
      differences concerning the location of the teeth in both marginal and internal
      fit (p<0.001). The measured gaps (types I-IV) revealed statistical differences
      between all types, when comparing SCs to the FDPs (p<0.001). SIGNIFICANCE: Single
      crowns showed significantly better accuracy of fit, compared to the 14-unit FDPs.
      However, both restorations showed clinically acceptable marginal and internal
      fit.

PMID- 24933231
TI  - Associations between the common HNF1A gene variant p.I27L (rs1169288) and risk of
      type 2 diabetes mellitus are influenced by weight.
AB  - AIM: The common variants p.I27L (rs1169288), p.A98V (rs1800574) and p.S487N
      (rs2464196) of the hepatocyte nuclear factor 1-alpha (HNF1A) gene have been
      inconsistently associated with impaired glucose tolerance and/or an increased
      risk of type 2 diabetes mellitus (T2DM). The present study aimed to investigate
      whether these associations are affected by weight. METHODS: A cross-sectional
      analysis was conducted among 861 Japanese subjects (males: 65.5%; 61.8+/
      12.3years) attending a health-screening programme. Interactive effects between
      HNF1A variants and weight status on risk of T2DM or dysglycaemic status were
      determined. RESULTS: The 27L variant carriers were at higher risk of T2DM and
      dysglycaemic status than non-carriers, but only in normal-weight subjects [odds
      ratio (OR): 2.04, P=0.03 and OR: 2.56, P=0.01, respectively]. An interactive
      effect of the p.I27L (rs1169288) variant and weight status on the risk of
      dysglycaemic status was found (P=0.04). Age, but not body mass index (BMI), was a
      risk factor for dysglycaemic status in the 27L carriers (OR: 1.05, P=0.0003),
      whereas BMI was a risk factor in non-carriers (OR: 1.23, P=0.008). No carriers of
      98V were identified, and 487N was not associated with either T2DM or dysglycaemic
      status in our study population. CONCLUSION: These findings suggest that the HNF1A
      p.I27L (rs1169288) variant may be a significant risk factor of T2DM in normal
      weight subjects and that earlier inconsistent results may have been due, in part,
      to subjects' weight status. Further investigations in larger cohorts are needed
      to verify these findings.

PMID- 24933232
TI  - Anti-sRAGE autoimmunity in obesity: downturn after bariatric surgery is
      independent of previous diabetic status.
AB  - AIM: Morbid obesity increases the risk of cardiovascular disease (CVD). The
      receptor for advanced glycation end-products (RAGE) is implicated in
      proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been
      proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were
      described and found to be increased in diseases where RAGE is overexpressed. This
      study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly
      obese patients. METHODS: After exclusion based on specific criteria, 150 subjects
      (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly
      recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE
      autoantibodies were measured before bariatric surgery. Sixty-nine patients were
      followed for up to 1year after gastric bypass, and their levels of sRAGE and anti
      sRAGE autoantibodies measured. The control group consisted of healthy blood
      donors. RESULTS: Compared with controls, baseline levels of sRAGE and anti-sRAGE
      autoantibodies were significantly higher in all obese patients independently of
      glucose regulation (P<0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE
      were decreased (P<0.001). The decrease in anti-sRAGE autoantibodies was
      correlated with an increase in high-density lipoprotein (HDL; P=0.02).
      CONCLUSION: Independently of previous diabetic status, morbid obesity increases
      sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a
      decrease in both titres. The decrease in anti-sRAGE correlates with an increase
      in HDL.

PMID- 24933233
TI  - Synthesis of the tetrasaccharide outer core fragment of Burkholderia multivorans
      lipooligosaccharide.
AB  - The first synthesis of the outer core fragment of Burkholderia multivorans
      lipooligosaccharide [beta-D-Glc-(1->3)-alpha-D-GalNAc-(1->3)-beta-D-GalNAc-(1->3)
      L-Rha] as alpha-allyl tetrasaccharide was accomplished. The glycosylations
      involving GalNAc units were studied in depth testing them under several
      conditions. This allowed the building of both the alpha- and the beta-configured
      glycosidic bonds by employing the same GalNAc glycosyl donor, thus considerably
      shortening the total number of synthetic steps. The target tetrasaccharide was
      synthesized with an allyl aglycone to allow its future conjugation with an
      immunogenic protein en route to the development of a synthetic neoglycoconjugate
      vaccine against the Burkholderia cepacia pathogens.

PMID- 24933234
TI  - Anomeric spirocycles by solvent incorporation: reactions of O-peracylated
      (glyculopyranose and glyculopyranosyl bromide)onamide derivatives with ketones.
AB  - Reactions of O-peracetylated (alpha-D-galacto-heptulopyranosyl bromide)onamide
      and O-perbenzoylated (alpha-D-gluco-heptulopyranosyl bromide)onamide with ketones
      in the presence of silver(I) salt promoters gave the corresponding O-peracylated
      1',5'-anhydro-D-glycitol-spiro-[1',5]-4-imino-2,2-disubstituted-1,3-dioxolanes.
      The D-galacto configured starting compounds furnished both spiro epimers, while
      the D-gluco counterparts yielded only configurationally inverted products. Under
      acidic conditions, O-perbenzoylated alpha-D-gluco-heptulopyranosonamide and
      ketones yielded the protected 1',5'-anhydro-D-glucitol-spiro-[1',5]-2,2
      disubstituted-oxazolidin-4-ones, which were O-debenzoylated by the Zemplen
      protocol. These compounds had no inhibition against rabbit muscle glycogen
      phosphorlyase b.

PMID- 24933235
TI  - Consumer knowledge and attitudes toward nutritional labels.
AB  - OBJECTIVE: To determine Mauritian consumers' attitudes toward nutritional labels
      based on the Kano model and to identify determinants of the use and understanding
      of nutrition labels. DESIGN: The researchers also used a Kano model questionnaire
      to determine consumers' attitudes toward nutrition labeling. SETTING: Four
      hundred consumers residing in Mauritius. PARTICIPANTS: Information was elicited
      via a questionnaire that assessed nutritional knowledge and information about the
      use and understanding of nutritional labels and demographic factors. MAIN OUTCOME
      MEASURES: Nutritional label use and understanding, nutrition knowledge, and
      association of demographic factors with label use. ANALYSIS: Statistical tests
      performed included 1-way ANOVA and independent samples t tests. RESULTS:
      Statistically significant relationships (P < .05) were found for nutritional
      knowledge and nutritional label usage with demographic factors. All demographic
      factors with the exception of gender were significantly associated (P < .05) with
      nutritional label understanding. Based on the outcome of the Kano survey, calorie
      content, trans fat content, protein content, and cholesterol content were found
      to be must-be attributes: that is, attributes that, when not present, result in
      consumer dissatisfaction. CONCLUSIONS AND IMPLICATIONS: Age, education, income,
      household size, and nutrition knowledge had an impact on nutritional label use.
      Health promoters should aim to increase the use of nutritional labels.

PMID- 24933236
TI  - A true branchial fistula in the context of branchiootic syndrome: challenges of
      diagnosis and management.
AB  - BACKGROUND: The presence of a branchial fistula with communication both
      internally and externally: a 'true' branchial fistula is rare, and may arise in
      the context of autosomal dominant conditions such as branchiootic syndrome and
      branchiootorenal syndrome. STUDY: We discuss the case of a true branchial
      fistula, which recurred after initial surgical excision, in a patient with
      branchiootic syndrome. The residual tract was dissected in a second operation
      through stepladder neck incisions and removed in toto via an intraoral approach.
      No renal abnormalities were detected on investigation with ultrasound.
      DISCUSSION: Incomplete excision of a branchial sinus is likely to cause
      recurrence however intraoperative visualisation of the tract can can sometimes
      prove challenging. An combined intraoral and external approach aids delineation
      and tract definition when there is a true branchial fistula and can therefore
      facilitate a complete excision. Suspicion of an hereditary aetiology should be
      raised in patients with bilateral or preauricular features, or a positive family
      history, which may then prompt additional renal and genetic investigation.

PMID- 24933237
TI  - Surgical treatment of severe hidradenitis suppurativa of the axilla:
      thoracodorsal artery perforator (TDAP) flap versus split skin graft.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease
      affecting the apocrine glands of the axillary, groin and mammary regions with
      significant physical and psychosocial sequelae. Surgical excision of the affected
      tissue is the gold standard treatment. Severe axillary HS is associated with high
      rates of recurrence and requires extensive surgical resection with challenging
      reconstruction associated with risk of post-operative complications. The most
      effective method for reconstruction of the axilla after excision of HS is yet to
      be identified. We present a prospective observational study comparing thoraco
      dorsal artery perforator (TDAP) flap and split-skin graft (SSG). METHODS: Over 4
      years, we enrolled 27 consecutive patients with Hurley's Stage III HS of the
      axilla who underwent surgical excision with reconstruction using either SSG
      (n=12) or TDAP flap reconstruction (n=15). We evaluated and compared
      intraoperative and post-operative data, quality of life (dermatology life quality
      index questionnaire) and pain/discomfort (visual analogue scale) before and after
      surgery. RESULTS: Patients who underwent TDAP flap reconstruction had
      significantly faster recovery, fewer complications and fewer overall number of
      procedures than those who underwent SSG reconstruction. All patients reported an
      improved quality of life (QOL) after their operation and the TDAP group showed
      significantly more improvement than the SSG group. All patients reported a
      reduction in pain/discomfort but there was no significant difference between
      groups. CONCLUSION: TDAP flap and SSG both improve QOL for patients with severe
      axillary HS. The TDAP flap showed greater benefits in terms of QOL, recovery,
      rate of complications and number of overall procedures.

PMID- 24933238
TI  - No need to cut the nerve in LD reconstruction to avoid jumping of the breast: a
      prospective randomized study.
AB  - BACKGROUND AND AIM: It has been shown that the myocutaneous latissimus dorsi flap
      volume and consistency remain mainly the same regardless the nerve is cut or not
      in breast reconstruction. It is controversial how big an impact the flap
      innervation has on the muscle activity of the flap. The aim of the study was to
      prospectively evaluate the influence of latissimus dorsi flap innervation on the
      functional and aesthetic outcome of delayed breast reconstruction. METHODS:
      Between 2007 and 2008, 28 breast reconstructions were performed and randomly
      divided into denervation group (surgical denervation by excision of 1 cm of
      proximal thoracodorsal nerve, n=14) and innervation group (thoracodorsal nerve
      saved intact, n=14). Patients were clinically evaluated and a questionnaire
      considering functional and aesthetic outcome was filled 1-year after operation.
      Muscular twitching, pain, tightness, shape and symmetry of the breasts were
      evaluated. In addition, the mobility of the shoulder joint on the operated side
      was evaluated and the patients self-estimated the activities of daily living.
      RESULTS: There was no significant difference in latissimus dorsi flap twitching,
      pain and tightness of the breast and symmetry and shape of the breasts between
      denervated and innervated groups. The shoulder joint mobility was not found to be
      changed significantly in either of the groups and there were no limitations in
      activities of daily living. CONCLUSIONS: Thoracodorsal nerve division or
      preservation does not significantly affect muscle contraction activity of the
      latissimus dorsi flap and distortion of the breast when latissimus dorsi muscle
      humeral insertion is also detached. Therefore, both cutting and saving the nerve
      are justified in latissimus dorsi flap breast reconstruction depending on whether
      the humeral insertion of the muscle is preserved intact or divided and the flap
      islanded. The study shows that there is no tangible benefit in dividing the nerve
      when the flap is islanded. Clinical trial has been registered in public trials
      registry. Trial registry name is 'The significance of latissimus dorsi flap
      innervation in delayed breast reconstruction'. Registration number is NCT01239524
      and URL is https://register.clinicaltrials.gov.

PMID- 24933239
TI  - The Tessier number 3 cleft: a report of 10 cases and review of literature.
AB  - The Tessier number 3 cleft is one of the most intricate and destructive of all
      facial clefts, presenting surgeons with a difficult task for reconstruction. We
      present a series of 10 patients with this rare cleft all treated by a single
      surgeon over 30 years. All patients with Tessier number 3 clefts treated between
      1978 and 2008 by the senior surgeon were reviewed. Demographic data and all
      associated clinical findings including cranial and extracranial anomalies were
      recorded. Methods used to reconstruct each patient were also noted. Seven males
      and three females were identified and age at initial treatment ranged from 12
      months to 12 years. Mean follow-up was 6.3 years. Multiple craniofacial anomalies
      were appreciated including other rare facial clefts, hypertelorbitism, lacrimal
      obstruction, anophthalmia, choanal atresia, and hemifacial microsomia. Amniotic
      banding was the most prominent extracranial finding noted in these patients.
      Tessier number 3 clefts can be associated with multiple other craniofacial
      anomalies making reconstruction challenging. Soft tissue and bony reconstruction
      must be considered separately, and a variety of tools may be employed to
      accomplish each goal. As the presentation can be highly variable, an
      individualized treatment plan must be made to meet each patient's specific needs.

PMID- 24933240
TI  - Unilateral approach for bilateral foramen decompression in minimally invasive
      transforaminal interbody fusion.
AB  - OBJECTIVE: To evaluate the efficiency and safety of a unilateral approach for
      bilateral foramen decompression in minimally invasive transforaminal lumbar
      interbody fusion (miTLIF) for the treatment of bilateral foraminal stenosis.
      METHODS: Treatment of 52 levels of bilateral foraminal stenosis in 48 patients
      was performed using a unilateral approach for bilateral foramen decompression in
      miTLIF. The foramen areas on bilateral sides, the cross-sectional areas of the
      dura mater, and the structural preservation of the multifidus muscle on bilateral
      sides were compared preoperatively and 1 year postoperatively. Visual analog
      scale scores of pain, 36-item short form health survey results, and complications
      were recorded after reviewing patient charts. Fusion rates were evaluated 1 year
      postoperatively. RESULTS: The average age of patients was 62.48 years. The mean
      follow-up period was 12.78 months. The foramen areas on bilateral sides and the
      cross-sectional area of the dura mater increased significantly postoperatively (P
      < 0.05). Structural preservation of the multifidus muscle was observed in 20 of
      54 levels (37%) on ipsilateral sides and in 48 of 54 levels (89%) on
      contralateral sides. No major complications were observed, and the incidences of
      minor complications and incidental durotomy were 28% and 4%, respectively.
      Improvements in average visual analog scale pain and 36-item short form health
      survey 6 (preoperative to 1 year postoperatively) scores were from 5.9 to 1.8 (P
      < 0.05) and from 51.3 to 71.3 (P < 0.01), respectively. The radiologic criteria
      of bony fusion were met by 40 patients (83%). CONCLUSIONS: A unilateral approach
      for bilateral foramen decompression in miTLIF provides a safe and efficient
      method for the treatment of bilateral foramen stenosis in patients with
      degenerative spinal disorders.

PMID- 24933241
TI  - Cost savings associated with antibiotic-impregnated shunt catheters in the
      treatment of adult and pediatric hydrocephalus.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) shunt infection is a major cause of
      morbidity and mortality in the treatment of hydrocephalus and is associated with
      significant medical cost. Several studies have demonstrated the efficacy of
      antibiotic-impregnated (AI) shunt catheters in reducing CSF shunt infection;
      however, providers remain reluctant to adopt AI catheters into practice because
      of the increased upfront cost. The objective of this study was to determine if
      the use of AI catheters provided cost savings in a large nationwide database.
      METHODS: Hospital discharge and billing records from the Premier Perspective
      Database from 2003-2009 were retrospectively reviewed to identify all adult and
      pediatric patients undergoing de novo ventricular shunt placement. The incidence
      of shunt infection within 1 year of implantation was determined. Shunt infection
      related cost was defined as all inpatient billing costs incurred during
      hospitalization for treatment of shunt infection. RESULTS: In 287 U.S. hospitals,
      10,819 adult (AI catheters, 963; standard catheters, 9856) and 1770 pediatric (AI
      catheters, 229; standard catheters, 1541) patients underwent ventricular shunt
      placement. AI catheters were associated with significant reduction in infection
      for both adult (2.2% vs. 3.6%, P = 0.02) and pediatric (2.6% vs. 7.1%, P < 0.01)
      patients. Total infection-related costs were $17,371,320 ($45,714 +/- $49,745 per
      shunt infection) for adult patients and $6,508,064 ($56,104 +/- $65,746 per shunt
      infection) for pediatric patients. Infection-related cost per 100 de novo shunts
      placed was $120,534 for AI catheters and $162,659 for standard catheters in adult
      patients and $165,087 for AI catheters and $395,477 for standard catheters in
      pediatric patients. CONCLUSIONS: In analysis of this large, nationwide database,
      AI catheters were found to be associated with a significant reduction in
      infection incidence, resulting in tremendous cost savings. AI catheters were
      associated with a cost savings of $42,125 and $230,390 per 100 de novo shunts
      placed in adult and pediatric patients, respectively.

PMID- 24933242
TI  - The efficacy of bypass surgery using a short interposition graft for the
      treatment of intracranial complex aneurysm.
AB  - OBJECTIVE: To evaluate the efficacy of a short interposition graft using
      saphenous vein or radial artery to connect the proximal superficial temporal
      artery and the M2 segments of the middle cerebral artery for the treatment of
      complex intracranial aneurysm. METHODS: From March 2007 to February 2012, short
      interposition graft bypass operations were performed in 13 patients with complex
      intracranial aneurysms. There were 6 ruptured aneurysms, including blood blister
      like aneurysms in 3 patients, giant aneurysms in 2 patients, and fusiform
      dissecting aneurysm in 1 patient. Among 7 patients with unruptured aneurysms,
      there were 5 giant aneurysms and 2 large fusiform aneurysms in the M2 segment.
      RESULTS: Parent artery occlusion with endovascular coiling (3 patients) or
      trapping by direct clipping (10 patients) was used to treat complex cerebral
      aneurysms. Complete occlusion of the aneurysm was demonstrated in 11 patients
      (85%); the other 2 patients did not demonstrate occlusion immediately
      postoperatively. Except for 2 patients who presented with poor-grade subarachnoid
      hemorrhage, patients (n = 11; 85%) demonstrated good scores on the Glasgow
      Outcome Scale. No new neurologic deficits developed in relation to insufficient
      blood flow through the bypass graft. In all 13 patients, graft patency was good
      at long-term follow-up (overall mean follow-up, 28.2 months). CONCLUSIONS:
      Superficial temporal artery-middle cerebral artery bypass surgery using a short
      interposition graft for intracranial complex aneurysms seems to be safe and
      efficient hemodynamically after occlusion of the parent artery. It could be
      regarded as a good alternative to high-flow bypass surgery.

PMID- 24933243
TI  - Parental acceptance of minimally invasive fetal and neonatal autopsy compared
      with conventional autopsy.
AB  - OBJECTIVE: To determine parental acceptance of minimally invasive autopsy (MIA)
      involving postmortem imaging and organ tissue sampling compared with conventional
      autopsy and to compare the acceptability of percutaneous versus laparoscopic
      guided biopsy. METHODS: Following termination of pregnancy parents were offered
      the option of traditional autopsy and subsequently interviewed about their
      acceptance of MIA. The McNemar test for paired samples was used to assess the
      difference in acceptance of MIA and conventional autopsy. The Wilcoxon signed
      rank test for paired samples was used to compare the acceptance score for
      percutaneous versus laparoscopic-guided biopsy. Logistic regression was selected
      to study the association of parental acceptance of conventional autopsy and MIA
      with different variables. RESULTS: Conventional autopsy was accepted by 42
      (60.0%) of the 70 parents. Regression analysis showed that non-Muslim faith was
      the only factor significantly associated with acceptance of conventional autopsy
      (p = 0.030). Of 28 parents who initially refused conventional autopsy, 13(46.4%)
      subsequently accepted MIA, increasing acceptance to 78.6% (p < 0.001). Regression
      analysis showed that none of the factors significantly affected MIA acceptance.
      Parents expressed no preference between postmortem percutaneous versus
      laparoscopic-guided biopsy (p = 0.061). CONCLUSION: Post-mortem imaging combined
      with systematic organ biopsies is highly acceptable among all parents independent
      of their religion and the method used for organ biopsy.

PMID- 24933246
TI  - Functional cognitive and cortical abnormalities in chronic and first-admission
      schizophrenia.
AB  - Evoked and induced event-related neural oscillations have recently been proposed
      as a key mechanism supporting higher-order cognition. Cognitive decay and
      abnormal electromagnetic sensory gating reliably distinguish schizophrenia (SZ)
      patients and healthy individuals, demonstrated in chronic (CHR) and first
      admission (FA) patients. Not yet determined is whether altered event-related
      modulation of oscillatory activity is manifested at early stages of SZ, thus
      reflects and perhaps embodies the development of psychopathology, and provides a
      mechanism for the gating deficit. The present study compared behavioral and
      functional brain measures in CHR and FA samples. Cognitive test performance
      (MATRICS Consortium Cognitive Battery, MCCB), neuromagnetic event-related fields
      (M50 gating ratio), and oscillatory dynamics (evoked and induced modulation of 8
      12Hz alpha) during a paired-click task were assessed in 35 CHR and 31 FA patients
      meeting the criteria for ICD-10 diagnoses of schizophrenia as well as 28 healthy
      comparison subjects (HC). Both patient groups displayed poorer cognitive
      performance, higher M50 ratio (poorer sensory gating), and less induced
      modulation of alpha activity than did HC. Induced alpha power decrease in
      bilateral posterior regions varied with M50 ratio in HC but not SZ, whereas
      orbitofrontal alpha power decrease was related to M50 ratio in SZ but not HC.
      Results suggest disruption of oscillatory dynamics at early stages of illness,
      which may contribute to deficient information sampling, memory updating, and
      higher cognitive functioning. 

PMID- 24933247
TI  - FKBP51 controls cellular adipogenesis through p38 kinase-mediated phosphorylation
      of GRalpha and PPARgamma.
AB  - Glucocorticoid receptor-alpha (GRalpha) and peroxisome proliferator-activated
      receptor-gamma (PPARgamma) are critical regulators of adipogenic responses. We
      have shown that FK506-binding protein 51 (FKBP51) represses the Akt-p38 kinase
      pathway to reciprocally inhibit GRalpha but stimulate PPARgamma by targeting
      serine 112 (PPARgamma) and serines 220 and 234 (GRalpha). Here, this mechanism is
      shown to be essential for GRalpha and PPARgamma control of cellular adipogenesis.
      In 3T3-L1 cells, FKBP51 was a prominent marker of the differentiated state and
      knockdown of FKBP51 showed reduced lipid accumulation and expression of
      adipogenic genes. Compared with wild-type (WT), FKBP51 knockout (51KO) mouse
      embryonic fibroblasts (MEFs) showed dramatic resistance to differentiation, with
      almost no lipid accumulation and greatly reduced adipogenic gene expression.
      These features were rescued by reexpression of FKBP51 in 51KO cells. 51KO MEFs
      exhibited reduced fatty acid synthase activity, increased sensitivity to GRalpha
      induced lipolysis, and reduced PPARgamma activity at adipogenic genes
      (adiponectin, CD36, and perilipin) but elevated GRalpha transrepression at these
      same genes. A p38 kinase inhibitor increased lipid content in WT cells and also
      restored lipid levels in 51KO cells, showing that elevated p38 kinase activity is
      a major contributor to adipogenic resistance in the 51KO cells. In 51KO cells,
      the S112A mutant of PPARgamma and the triple S212A/S220A/S234A mutant of GRalpha
      both increased lipid accumulation, identifying these residues as targets of the
      FKBP51/p38 axis. Our combined investigations have uncovered FKBP51 as a key
      regulator of adipogenesis via the Akt-p38 pathway and as a potential target in
      the treatment of obesity and related disorders. 

PMID- 24933244
TI  - Sleep quality and body mass index in college students: the role of sleep
      disturbances.
AB  - OBJECTIVE: Obesity and its comorbidities have emerged as a leading public health
      concern. The aim of this study was to explore the relationship between body mass
      index (BMI) and sleep patterns, including duration and disturbances. METHODS: A
      convenience sample of 515 college students completed an online survey consisting
      of the Pittsburgh Sleep Quality Index (PSQI), and self-reported height and weight
      to calculate BMI. Univariate and multivariate logistic regression analyses were
      performed using components of the PSQI as predictors of overweight (BMI >= 25).
      RESULTS: One-third of the participants had BMI >= 25, and 51% were poor-quality
      sleepers (PSQI > 5). Controlling for age and sex, only sleep disturbances were
      associated with overweight (odds ratio = 1.66, 95% confidence interval [1.08,
      2.57]). CONCLUSIONS: Sleep disturbances, rather than sleep duration, predicted
      overweight among young adults; this is consistent with the most recent evidence
      in the literature. These findings support expanding the scope of wellness
      programs to promote healthy sleep among students.

PMID- 24933248
TI  - FKBP51 reciprocally regulates GRalpha and PPARgamma activation via the Akt-p38
      pathway.
AB  - FK506-binding protein 51 (FKBP51) is a negative regulator of glucocorticoid
      receptor-alpha (GRalpha), although the mechanism is unknown. We show here that
      FKBP51 is also a chaperone to peroxisome proliferator-activated receptor-gamma
      (PPARgamma), which is essential for activity, and uncover the mechanism
      underlying this differential regulation. In COS-7 cells, FKBP51 overexpression
      reduced GRalpha activity at a glucocorticoid response element-luciferase
      reporter, while increasing PPARgamma activity at a peroxisome proliferator
      response element reporter. Conversely, FKBP51-deficient (knockout) (51KO) mouse
      embryonic fibroblasts (MEFs) showed elevated GRalpha but reduced PPARgamma
      activities compared with those in wild-type MEFs. Phosphorylation is known to
      exert a similar pattern of reciprocal modulation of GRalpha and PPARgamma.
      Knockdown of FKBP51 in 3T3-L1 preadipocytes increased phosphorylation of
      PPARgamma at serine 112, a phospho-residue that inhibits activity. In 51KO cells,
      elevated phosphorylation of GRalpha at serines 220 and 234, phospho-residues that
      promote activity, was observed. Because FKBP51 is an essential chaperone to the
      Akt-specific phosphatase PH domain leucine-rich repeat protein phosphatase, Akt
      signaling was investigated. Elevated Akt activation and increased activation of
      p38 kinase, a downstream target of Akt that phosphorylates GRalpha and PPARgamma,
      were seen in 51KO MEFs, causing activation and inhibition, respectively.
      Inactivation of p38 with PD169316 reversed the effects of FKBP51 deficiency on
      GRalpha and PPARgamma activities and reduced PPARgamma phosphorylation. Last,
      loss of FKBP51 caused a shift of PPARgamma from cytoplasm to nucleus, as
      previously shown for GRalpha. A model is proposed in which FKBP51 loss
      reciprocally regulates GRalpha and PPARgamma via 2 complementary mechanisms:
      activation of Akt-p38-mediated phosphorylation and redistribution of the
      receptors to the nucleus for direct targeting by p38. 

PMID- 24933252
TI  - Optimal immunosuppression for HIV-positive kidney transplants: long-term
      randomized controlled trials needed.

PMID- 24933253
TI  - The authors' reply.

PMID- 24933249
TI  - Research resource: Gene profiling of G protein-coupled receptors in the arcuate
      nucleus of the female.
AB  - The hypothalamic arcuate nucleus controls many critical homeostatic functions
      including energy homeostasis, reproduction, and motivated behavior. Although G
      protein-coupled receptors (GPCRs) are involved in the regulation of these
      functions, relatively few of the GPCRs have been identified specifically within
      the arcuate nucleus. Here, using TaqMan low-density arrays we quantified the mRNA
      expression of nonolfactory GPCRs in mouse arcuate nucleus. An unprecedented
      number of GPCRs (total of 292) were found to be expressed, of which 183 were
      known and 109 were orphan GPCRs. The known GPCR genes expressed were classified
      into several functional clusters including hormone/neurotransmitter, growth
      factor, angiogenesis and vasoactivity, inflammation and immune system, and lipid
      messenger receptors. The plethora of orphan genes expressed in the arcuate
      nucleus were classified into 5 structure-related classes including class A
      (rhodopsin-like), class B (adhesion), class C (other GPCRs), nonsignaling 7
      transmembrane chemokine-binding proteins, and other 7-transmembrane proteins.
      Therefore, for the first time, we provide a quantitative estimate of the numerous
      GPCRs expressed in the hypothalamic arcuate nucleus. Finally, as proof of
      principle, we documented the expression and function of one of these receptor
      genes, the glucagon-like peptide 1 receptor (Glp1r), which was highly expressed
      in the arcuate nucleus. Single-cell RT-PCR revealed that Glp1r mRNA was localized
      in proopiomelanocortin neurons, and using whole-cell recording we found that the
      glucagon-like peptide 1-selective agonist exendin-4 robustly excited
      proopiomelanocortin neurons. Thus, the quantitative GPCR data emphasize the
      complexity of the hypothalamic arcuate nucleus and furthermore provide a valuable
      resource for future neuroendocrine/endocrine-related experiments. 

PMID- 24933254
TI  - Multiple Aspergillus brain abscesses after liver transplantation.

PMID- 24933255
TI  - Update on the provisional estimation of developing iatrogenic variant Creutzfeldt
      Jakob disease from human islet cell transplantation procedures.

PMID- 24933256
TI  - Late donor bone marrow failure after allogeneic hematopoietic stem cell
      transplantation.

PMID- 24933257
TI  - Measurement of cooling and warming rates in vitrification-based plant
      cryopreservation protocols.
AB  - Cryopreservation protocols include the use of additives and pretreatments aimed
      to reduce the probability of ice nucleation at all temperatures, mainly through
      micro-viscosity increase. Still, there is a risk of ice formation in the
      temperature region comprised between the equilibrium freezing (Tf ) and the glass
      transition (TG ) temperatures. Consequently, fast cooling and warming, especially
      in this region, is a must to avoid ice-derived damage. Vitrification and droplet
      vitrification techniques, frequently used cryopreservation protocols based in
      fast cooling, were studied, alongside with the corresponding warming procedures.
      A very fast data acquisition system, able to read very low temperatures, down to
      that of liquid nitrogen, was employed. Cooling rates, measured between -20
      degrees C and -120 degrees C, ranged from ca. 5 degrees C s(-1) to 400 degrees C
      s(-1) , while warming rates spanned from ca. 2 degrees C s(-1) to 280 degrees C
      s(-1) , for the different protocols and conditions studied. A wider measuring
      window (0 degrees C to -150 degrees C) produced lower rates for all cases. The
      cooling and warming rates were also related to the survival observed after the
      different procedures. Those protocols with the faster rates yielded the highest
      survival percentages.

PMID- 24933258
TI  - Control of protein function through optochemical translocation.
AB  - Controlled manipulation of proteins and their function is important in almost all
      biological disciplines. Here, we demonstrate control of protein activity with
      light. We present two different applications-light-triggered transcription and
      light-triggered protease cleavage-both based on the same concept of protein
      mislocation, followed by optochemically triggered translocation to an active
      cellular compartment. In our approach, we genetically encode a photocaged lysine
      into the nuclear localization signal (NLS) of the transcription factor SATB1.
      This blocks nuclear import of the protein until illumination induces caging group
      removal and release of the protein into the nucleus. In the first application,
      prepending this NLS to the transcription factor FOXO3 allows us to optochemically
      switch on its transcription activity. The second application uses the developed
      light-activated NLS to control nuclear import of TEV protease and subsequent
      cleavage of nuclear proteins containing TEV cleavage sites. The small size of the
      light-controlled NLS (only 20 amino acids) minimizes impact of its insertion on
      protein function and promises a general approach to a wide range of optochemical
      applications. Since the light-activated NLS is genetically encoded and optically
      triggered, it will prove useful to address a variety of problems requiring
      spatial and temporal control of protein function, for example, in stem-cell,
      developmental, and cancer biology. 

PMID- 24933259
TI  - Primary liver cells cultured on carbon nanotube substrates for liver tissue
      engineering and drug discovery applications.
AB  - Here, we explore the use of two- and three-dimensional scaffolds of multiwalled
      carbon nanotubes (MWNTs) for hepatocyte cell culture. Our objective is to study
      the use of these scaffolds in liver tissue engineering and drug discovery. In our
      experiments, primary rat hepatocytes, the parenchymal (main functional) cell type
      in the liver, were cultured on aligned nanogrooved MWNT sheets, MWNT yarns, or
      standard 2-dimensional culture conditions as a control. We find comparable cell
      viability between all three culture conditions but enhanced production of the
      hepatocyte-specific marker albumin for cells cultured on MWNTs. The basal
      activity of two clinically relevant cytochrome P450 enzymes, CYP1A2 and CYP3A4,
      are similar on all substrates, but we find enhanced induction of CYP1A2 for cells
      on the MWNT sheets. Our data thus supports the use of these substrates for
      applications including tissue engineering and enhancing liver-specific functions,
      as well as in in vitro model systems with enhanced predictive capability in drug
      discovery and development. 

PMID- 24933260
TI  - Barriers to mental health treatment for military wives.
AB  - OBJECTIVE: An Internet-based survey sought information about barriers to mental
      health services for military wives. METHODS: On the basis of qualitative work, an
      Internet-based program was created to identify military wives who may have major
      depressive disorder. RESULTS: Women (N=569, ages 18 to 56) were recruited from 45
      states and eight foreign countries. Most participants (78%) reported mild to
      severe depression. Many (44%) reported unaddressed mental health needs. Barriers
      included inability to attend daytime appointments (38%), inability to find a
      counselor who understands the needs of military spouses (35%), inability to find
      a counselor the participant could trust (29%), concerns about confidentiality
      (26%), and lack of knowledge about where to get services (25%). The barriers
      reported differed markedly from those described by distressed women in the
      general population. CONCLUSIONS: Military wives are an underserved population.
      Knowledge of military culture is essential for civilian mental health providers
      working with military wives.

PMID- 24933261
TI  - Structure of kif14: an engaging molecular motor.

PMID- 24933262
TI  - Template-free synthesis of mesoporous polymers.
AB  - Mesoporous polyacrylamides (PAMs) with tunable porosities were synthesized in 1
      alkyl-3-methylimidazolium tetrafluoroborates ([Cnmim][BF4], n = 4, 6, 8, 10). The
      as-synthesized PAM was used as a support for Pd nanoparticles and the Pd/PAM
      composite showed high catalytic activity and selectivity for the hydrogenation of
      p-chloronitrobenzene reaction to yield p-chloroaniline. 

PMID- 24933263
TI  - Individual effects of seasonal changes, visitor density, and concurrent bear
      behavior on stereotypical behaviors in captive polar bears (Ursus maritimus).
AB  - Stereotypical behaviors in captive polar bears (Ursus maritimus) can be
      detrimental to their welfare. These behaviors can be reduced through enrichment
      programs but are often not completely eliminated, so identifying potential
      triggers is important. The present study investigated the influences of seasonal
      changes, visitor density, and concurrent bear activity on stereotypical behaviors
      exhibited by 3 captive polar bears at the Toronto Zoo. All bears exhibited these
      behaviors; however, individual differences were found in duration and form. The
      male exhibited less stereotypical behavior during spring, and the females
      exhibited less stereotypical behavior during winter. An increase in visitor
      density was associated with more stereotypical behavior in 1 female but less
      stereotypical behavior in the other 2 bears. All bears engaged in more
      stereotypical behaviors when the other bears were inactive, and 1 female engaged
      in more stereotypical behaviors when the other bears were out of sight. Further,
      when conspecifics were active, all bears engaged in less stereotypical behaviors.
      Given the variability among individual bears, future enrichment programs must be
      tailored to the needs of individuals to maximize efficacy. 

PMID- 24933264
TI  - Exploring universal patterns in human home-work commuting from mobile phone data.
AB  - Home-work commuting has always attracted significant research attention because
      of its impact on human mobility. One of the key assumptions in this domain of
      study is the universal uniformity of commute times. However, a true comparison of
      commute patterns has often been hindered by the intrinsic differences in data
      collection methods, which make observation from different countries potentially
      biased and unreliable. In the present work, we approach this problem through the
      use of mobile phone call detail records (CDRs), which offers a consistent method
      for investigating mobility patterns in wholly different parts of the world. We
      apply our analysis to a broad range of datasets, at both the country (Portugal,
      Ivory Coast, and Saudi Arabia), and city (Boston) scale. Additionally, we compare
      these results with those obtained from vehicle GPS traces in Milan. While
      different regions have some unique commute time characteristics, we show that the
      home-work time distributions and average values within a single region are indeed
      largely independent of commute distance or country (Portugal, Ivory Coast, and
      Boston)-despite substantial spatial and infrastructural differences. Furthermore,
      our comparative analysis demonstrates that such distance-independence holds true
      only if we consider multimodal commute behaviors-as consistent with previous
      studies. In car-only (Milan GPS traces) and car-heavy (Saudi Arabia) commute
      datasets, we see that commute time is indeed influenced by commute distance.
      Finally, we put forth a testable hypothesis and suggest ways for future work to
      make more accurate and generalizable statements about human commute behaviors. 

PMID- 24933265
TI  - Age-related changes in intracortical inhibition are mental-cognitive state
      dependent.
AB  - INTRODUCTION: This study aimed to assess the impact of aging and 'state
      dependency' on cortical excitability. Two studies investigated these factors
      using a motor task and found that the age-related differences observed at rest
      disappeared in the task condition. However, as both their tasks and excitability
      measurements involved the motor cortex, their results could be specific only to
      the motor system. To overcome this problem, the present study used a cognitive
      task to control mental state. METHOD: Intracortical inhibition/facilitation
      (ICI/ICF) were assessed in young and older adults at rest and during the
      cognitive task. The cortical silent period (CSP) was also evaluated. RESULTS: ICI
      and CSP were reduced with aging. However, ICI differences between young and old
      people disappeared when they performed the cognitive task. CONCLUSION: Age and
      mental state modify cortical excitability. Taking these factors into
      consideration is crucial to clinical research using cortical excitability as a
      possible biomarker of pathology.

PMID- 24933266
TI  - Quantitative proteome profiling of CNS-infiltrating autoreactive CD4+ cells
      reveals selective changes during experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a murine model of multiple
      sclerosis, a chronic neurodegenerative and inflammatory autoimmune condition of
      the central nervous system (CNS). Pathology is driven by the infiltration of
      autoreactive CD4(+) lymphocytes into the CNS, where they attack neuronal sheaths
      causing ascending paralysis. We used an isotope-coded protein labeling approach
      to investigate the proteome of CD4(+) cells isolated from the spinal cord and
      brain of mice at various stages of EAE progression in two EAE disease models:
      PLP139-151-induced relapsing-remitting EAE and MOG35-55-induced chronic EAE,
      which emulate the two forms of human multiple sclerosis. A total of 1120 proteins
      were quantified across disease onset, peak-disease, and remission phases of
      disease, and of these 13 up-regulated proteins of interest were identified with
      functions relating to the regulation of inflammation, leukocyte adhesion and
      migration, tissue repair, and the regulation of transcription/translation.
      Proteins implicated in processes such as inflammation (S100A4 and S100A9) and
      tissue repair (annexin A1), which represent key events during EAE progression,
      were validated by quantitative PCR. This is the first targeted analysis of
      autoreactive cells purified from the CNS during EAE, highlighting fundamental
      CD4(+) cell-driven processes that occur during the initiation of relapse and
      remission stages of disease. 

PMID- 24933267
TI  - Marriage, cohabitation, and men's use of preventive health care services.
AB  - Previous research has demonstrated that married men are more likely than not
      married men to seek preventive health care services because their spouses
      encourage them to do so (1,2). It was not known, however, whether cohabiting
      partners of not-married men play a health-promoting role similar to that of
      spouses. With data from the 2011-2012 National Health Interview Survey (NHIS),
      selected measures of preventive health care service use were compared for three
      groups of men aged 18-64: married men (defined as those living with a spouse),
      cohabiting men (defined as those living with a partner who is not a spouse), and
      other not-married men. The consistency of observed differences by age and health
      insurance coverage status was also investigated.

PMID- 24933268
TI  - Shear wave elastography contribution in ultrasound diagnosis management of breast
      lesions.
AB  - PURPOSE: To determine the diagnosis performance of shear wave elastography in the
      differentiation of benign and malignant breast lesions and the factors
      influencing the elasticity values. To suggest an appropriate management of breast
      lesions using the ultrasound-elastography combination. PATIENTS AND METHODS:
      Monocentric retrospective study of 167 breast lesions classified by conventional
      ultrasound as BI-RADS category 3 or higher that underwent an elastography study
      and histological analysis. RESULTS: The analysis of qualitative parameters,
      according to the classification established in this study, allows us to obtain a
      sensitivity of 91.1% and a specificity of 92.3%. These values are very close to
      or better than the quantitative parameters Emax and Emean. Different Emax
      thresholds values were established based on the long axis of the lesion and its
      palpable character, which appeared to be significant factors influencing
      elasticity. The management of breast lesions by combining ultrasound and
      elastography, as proposed here, allows us to keep the sensitivity of an
      ultrasound (96%), while doubling its specificity (86.2% versus 43.1%).
      CONCLUSION: With the complementary nature of their performance, the combination
      of conventional ultrasound and shear wave elastography can improve the management
      of breast lesions. The qualitative classification proposed appears to be relevant
      assistance in lesion characterization.

PMID- 24933269
TI  - Advanced technologies applied to physiopathological analysis of central nervous
      system aneurysms and vascular malformations.
AB  - While depiction and definition of morphological and architectural characteristics
      of CNS vascular disorders remains the first step of an MR analysis, emerging
      imaging techniques offer new functional information that might help to
      characterize rupture risk of CNS vascular disorders. Two main orientations are
      suggested by recent studies: inflammation of the vessel wall and analysis of
      physical constraints of blood flow using 4D flow imaging (shear parietal). This
      paper will focus on radiological application of 4D flow imaging and inflammation
      imaging, in the characterization of potential prognostic markers of CNS vascular
      disorders. We will review the basic technical considerations of 4D flow MRA,
      inflammation imaging and discuss their applications in CNS vascular disorders:
      aneurysms, arteriovenous malformation, dural arteriovenous fistulas. We will
      illustrate their potential in the development of individual rupture risk criteria
      in brain vascular disorders. 

PMID- 24933270
TI  - Treatment of hepatic and pulmonary metastases with radiofrequency.
AB  - Although metastatic disease indicates diffusion of a cancer at a distance from
      its site of origin, in some cases pulmonary and hepatic metastases are isolated
      and slowly progressive, making them suitable for local treatment. Thermo-ablation
      techniques are associated with low morbidity and reduced collateral parenchymal
      damage; they therefore play an important role in such patients, where the disease
      is slow and chronic, requiring repeated local treatments. Unlike radiotherapy, a
      second treatment is possible in the event of local failure. 

PMID- 24933271
TI  - Exposure to mutagenic disinfection byproducts leads to increase of antibiotic
      resistance in Pseudomonas aeruginosa.
AB  - Bacterial antibiotic resistance (BAR) in drinking water has become a global issue
      because of its risks on the public health. Usually, the antibiotic concentrations
      in drinking water are too low to select antibiotic resistant strains effectively,
      suggesting that factors other than antibiotics would contribute to the emergence
      of BAR. In the current study, the impacts of mutagenic disinfection byproducts
      (DBPs) on BAR were explored, using four typical DBPs: dibromoacetic acid,
      dichloroacetonitrile, potassium bromate, and 3-chloro-4-(dichloromethyl)-5
      hydroxy-2(5H)-furanone (MX). After exposure to DBPs, resistances to 10 individual
      antibiotics and multiple antibiotics were both raised by various levels,
      norfloxacin and polymycin B resistances were enhanced even greater than 10-fold
      compared with control. MX increased the resistance most observably in the
      selected DBPs, which was consistent with its mutagenic activity. The resistant
      mutants showed hereditary stability during 5-day culturing. The increase of BAR
      was caused by the mutagenic activities of DBPs, since mutation frequency declined
      by adding ROS scavenger. Mutagenesis was further confirmed by sequencing of the
      related genes. Our study indicated that mutagenic activities of the selected DBPs
      could induce antibiotic resistance, even multidrug resistance, which may
      partially explain the lack of agreement between BAR and antibiotic levels in
      drinking water. 

PMID- 24933272
TI  - No one knew.

PMID- 24933273
TI  - A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in
      ligand-protein complexes when a halogenated ligand is an H-bond donor.
AB  - Halogen bonding in ligand-protein complexes is currently widely exploited, e.g.
      in drug design or supramolecular chemistry. But little attention has been
      directed to other effects that may result from replacement of a hydrogen by a
      strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between
      protein and ligand demonstrates that the length of a hydrogen bond depends on the
      type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a
      protein and a halogenated ligand are visibly shorter than those estimated for the
      same family of proteins in complexes with non-halogenated ligands. Taking into
      account the effect of halogenation on hydrogen bonding is thus important when
      evaluating structural and/or energetic parameters of ligand-protein complexes.
      All these observations are consistent with the concept that halogenation
      increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes
      them better, i.e. stronger, H-bond donors. 

PMID- 24933275
TI  - Using a five-gene phylogeny to test morphology-based hypotheses of Smittium and
      allies, endosymbiotic gut fungi (Harpellales) associated with arthropods.
AB  - Smittium, one of the first described genera of gut fungi, is part of a larger
      group of endosymbiotic microorganisms (Harpellales) that live predominantly in
      the digestive tracts of aquatic insects. As a diverse and species-rich taxon,
      Smittium has helped to advance our understanding of the gut fungi, in part due to
      the relative success of attempts to culture species of Smittium as compared to
      other members of Harpellales. Approximately 40% of the 81 known species of
      Smittium have been cultured. This is the first Smittium multigene dataset and
      phylogenetic analysis, using the 18S and 28S rRNA genes, as well as RPB1, RPB2,
      and MCM7 translated protein sequences. Several well-supported clades were
      recovered within Smittium. One includes the epitype S. mucronatum (the "True
      Smittium" clade), and another contains many species including S. simulii and S.
      orthocladii (the "Parasmittium" clade). Ancestral states were reconstructed for
      holdfast shape, thallus branching type, as well as asexual (trichospore) and
      sexual (zygospore) spore morphology. Two of these characters, holdfast shape and
      trichospore morphology, supported the split of the two main clades revealed by
      the molecular phylogeny, suggesting these are natural clades and these traits may
      have evolutionary and perhaps ecological significance. 

PMID- 24933274
TI  - Rule-based design of synthetic transcription factors in eukaryotes.
AB  - To design and build living systems, synthetic biologists have at their disposal
      an increasingly large library of naturally derived and synthetic parts. These
      parts must be combined together in particular orders, orientations, and spacings
      to achieve desired functionalities. These structural constraints can be viewed as
      grammatical rules describing how to assemble parts together into larger
      functional units. Here, we develop a grammar for the design of synthetic
      transcription factors (sTFs) in eukaryotic cells and implement it within GenoCAD,
      a Computer-Aided Design (CAD) software for synthetic biology. Knowledge derived
      from experimental evidence was captured in this grammar to guide the user to
      create designer transcription factors that should operate as intended. The
      grammar can be easily updated and refined as our experience with using sTFs in
      different contexts increases. In combination with grammars that define other
      synthetic systems, we anticipate that this work will enable the more reliable,
      efficient, and automated design of synthetic cells with rich functionalities. 

PMID- 24933277
TI  - The attentional boost effect in schizophrenia.
AB  - The present study reports 2 experiments examining the Attentional Boost Effect
      (ABE) in schizophrenic patients and matched healthy controls, using visual and
      verbal materials. The ABE refers to the surprising finding that, in a divided
      attention condition, images and words encoded with targets are remembered better
      than images and words encoded with distractors. Unlike controls (who showed the
      typical ABE), schizophrenic patients reported no memory advantage for stimuli
      presented together with targets in the divided attention condition. On the other
      hand, the interference effect on the recognition of stimuli presented with
      distractors was not exacerbated in patients (as compared with controls). In line
      with the dual-task interaction model proposed by Swallow and Jiang (2013), the
      absence of a significant facilitation indicates that schizophrenic patients have
      a deficit in the process of attentional enhancement triggered by target
      detection. A number of neural mechanisms potentially underlying this impairment
      are discussed, as well as implications for the characterization of the
      attentional deficits involved in schizophrenia.

PMID- 24933276
TI  - Cognitive load and emotional processing in generalized anxiety disorder:
      electrocortical evidence for increased distractibility.
AB  - Generalized anxiety disorder (GAD) may be characterized by emotion regulation
      deficits attributable to an imbalance between top-down (i.e., goal-driven) and
      bottom-up (i.e., stimulus-driven) attention. In prior work, these attentional
      processes were examined by presenting unpleasant and neutral pictures within a
      working memory paradigm. The late positive potential (LPP) measured attention
      toward task-irrelevant pictures. Results from this prior work showed that working
      memory load reduced the LPP across participants; however, this effect was
      attenuated for individuals with greater self-reported state anxiety, suggesting
      reduced top-down control. In the current study, the same paradigm was used with
      106 medication-free female participants-71 with GAD and 35 without GAD.
      Unpleasant pictures elicited larger LPPs, and working memory load reduced the
      picture-elicited LPP. Compared with healthy controls, participants with GAD
      showed large LPPs to unpleasant pictures presented under high working memory
      load. Self-reported symptoms of anhedonic depression were related to a reduced
      effect of working memory load on the LPP elicited by neutral pictures. These
      results indicate that individuals with GAD show less flexible modulation of
      attention when confronted with unpleasant stimuli. Furthermore, among those with
      GAD, anhedonic depression may broaden attentional deficits to neutral
      distracters.

PMID- 24933279
TI  - Integrating oddity traits in a dimensional model for personality pathology
      precursors.
AB  - Current dimensional measures of early personality pathology (e.g., the
      Dimensional Personality Symptom Item Pool, DIPSI; De Clercq, De Fruyt, Van
      Leeuwen, & Mervielde, 2006) describe personality difficulties within a 4
      dimensional framework. The present study corroborates recent evidence on the
      relevance of including a 5th Oddity-related domain for a more comprehensive
      description of personality pathology, and presents the construction of an
      empirically based taxonomy of early Oddity features. Psychometric and factor
      analytic procedures were conducted on self- and maternal ratings of adolescents
      (N = 434), resulting in 4 internally consistent facets that empirically collapse
      in 1 higher-order "Oddity" factor. From a structural perspective, this Oddity
      factor emerged as a clear 5th factor beyond the earlier proposed 4-dimensional
      structure of child and adolescent personality pathology. Significant associations
      of Oddity with both general and maladaptive trait equivalents support the
      construct validity of this 5th factor, and challenge current hypotheses on the
      applicability of the continuity hypothesis on general and maladaptive trait
      variance within the openness field. The results further suggest that Oddity
      traits are meaningfully associated with general psychopathology at a young age.
      These findings are discussed in terms of the importance of including a 5th Oddity
      related factor in dimensional models of developmental personality pathology in
      order to acquire a more comprehensive description of the building blocks that
      underlie early personality difficulties.

PMID- 24933278
TI  - The many faces of affect: a multilevel model of drinking frequency/quantity and
      alcohol dependence symptoms among young adults.
AB  - This research tested a multilevel structural equation model of associations
      between 3 aspects of affective functioning (state affect, trait affect, and
      affective lability) and 3 alcohol outcomes (likelihood of drinking, quantity on
      drinking days, and dependence symptoms) in a sample of 263 college students.
      Participants provided 49 days of experience sampling data over 1.3 years in a
      longitudinal burst design. Within-person results: At the daily level, positive
      affect was directly associated with greater likelihood and quantity of alcohol
      consumption. Daily negative affect was directly associated with higher
      consumption on drinking days and with higher dependence symptoms. Between-person
      direct effects: Affect lability was associated with higher trait negative, but
      not positive, affect. Trait positive affect was inversely associated with the
      proportion of drinking days, whereas negative affectivity predicted a greater
      proportion of drinking days. Affect lability exhibited a direct association with
      dependence symptoms. Between-person indirect effects: Trait positive affect was
      associated with fewer dependence symptoms via proportion of drinking days. Trait
      negative affect was associated with greater dependence symptoms via proportion of
      drinking days. The results distinguish relations of positive and negative affect
      to likelihood versus amount of drinking and state versus trait drinking outcomes,
      and highlight the importance of affect variability for predicting alcohol
      dependence symptoms.

PMID- 24933280
TI  - Out of the frying pan, into the fire: mixed affective reactions to social
      proximity in borderline and avoidant personality disorders in daily life.
AB  - Social proximity typically helps individuals meet their belongingness needs, but
      several forms of psychopathology, including borderline and avoidant personality
      disorders (BPD and APD, respectively) are characterized by social difficulties.
      This experience-sampling study is one of the first to directly investigate the
      affective reactions of individuals with BPD and APD (compared with healthy
      controls [HC]) to social proximity in daily life. We examined both person-level
      and day-level reactions. At the person level, the rate of social proximity across
      the diary period was associated with diminished feelings of rejection, isolation,
      shame, and dissociation in the HC group. In contrast, it was not associated with
      any affective reaction in the BPD group, and was associated with decreased
      rejection and isolation on the one hand, but also with increased anxiety in the
      APD group. At the day level, we used multilevel regression to examine affective
      reactions when in social proximity. The HC group showed a consistent benefit when
      in social proximity. In contrast, both PD groups exhibited mixed affective
      reactions to social proximity; specifically, benefits (increased positive affect,
      decreased rejection, isolation, and dissociation) were interspersed with costs
      (increased shame for both PD groups; increased anger for BPD; increased anxiety
      for APD). The mixed reactions found in both PDs may contribute to the disturbed
      relationships of individuals with these disorders.

PMID- 24933281
TI  - Network analysis of persistent complex bereavement disorder in conjugally
      bereaved adults.
AB  - Persistent complex bereavement disorder (PCBD) is a bereavement-specific syndrome
      characterized by prolonged and impairing grief. Most research on this syndrome
      rests on the traditional latent variable model, whereby symptoms reflect an
      underlying entity. The network (or causal system) approach offers an alternative
      framework for understanding PCBD that does not suffer from limitations inherent
      in the latent entity approach. The network approach to psychopathology
      conceptualizes the relation between symptoms and disorder as mereological, not
      reflective. That is, symptoms do not reflect an inferred, unobservable category
      or dimension, but rather are themselves constitutive of the disorder.
      Accordingly, we propose that PCBD constitutes a causal system of mutually
      reinforcing symptoms that arise following the death of a loved one and settle
      into a pathological equilibrium. In this study, we used data from the Changing
      Lives of Older Couples database to identify symptoms central to PCBD, to
      distinguish the PCBD network from an overlapping but distinct network of
      depression symptoms, and to examine how previously identified risk factors may
      contribute to the maintenance or development of PCBD. Together, these findings
      provide an important first step toward understanding the nature and etiology of
      the PCBD network.

PMID- 24933283
TI  - Change in emotion regulation strategy use and its impact on adolescent
      nonsuicidal self-injury: a three-year longitudinal analysis using latent growth
      modeling.
AB  - This longitudinal study examines the extent to which changes in the use of
      cognitive reappraisal, expressive suppression, and rumination impact on
      frequency, duration, and medical severity of nonsuicidal self-injury (NSSI) among
      adolescents. Data from 3,143 predominantly female high school students recruited
      from 40 Australian secondary schools were analyzed using latent growth curve
      modeling. Significant differences in the psychological factors between the 555
      participants with a history of NSSI and non-self-injurers were reported at
      baseline. Self-injurers experienced significantly greater accumulation of life
      stressors over time compared with non-self-injurers. After controlling for
      adverse life events, psychological distress and other emotion regulation
      strategies, use of cognitive reappraisal at baseline was associated with less
      severe NSSI presentations, and slower growth in medical severity of NSSI over
      time. Findings indicate that while both cohorts have similar emotion regulation
      trajectories, adolescents who self-injure start off at a disadvantage and have a
      propensity to engage in less helpful processes that tend to heighten negative
      emotional states. Results recommend increasing focus on improving adolescents'
      frequency and skills in use of cognitive reappraisal in efforts to reduce NSSI
      among this population.

PMID- 24933282
TI  - Response monitoring and adjustment: differential relations with psychopathic
      traits.
AB  - Studies on the relation between psychopathy and cognitive functioning often show
      mixed results, partially because different factors of psychopathy have not been
      considered fully. Based on previous research, we predicted divergent results
      based on a 2-factor model of psychopathy (interpersonal-affective traits and
      impulsive-antisocial traits). Specifically, we predicted that the unique variance
      of interpersonal-affective traits would be related to increased monitoring (i.e.,
      error-related negativity) and adjusting to errors (i.e., posterror slowing),
      whereas impulsive-antisocial traits would be related to reductions in these
      processes. Three studies using a diverse selection of assessment tools, samples,
      and methods are presented to identify response monitoring correlates of the 2
      main factors of psychopathy. In Studies 1 (undergraduates), 2 (adolescents), and
      3 (offenders), interpersonal-affective traits were related to increased
      adjustment following errors and, in Study 3, to enhanced monitoring of errors.
      Impulsive-antisocial traits were not consistently related to error adjustment
      across the studies, although these traits were related to a deficient monitoring
      of errors in Study 3. The results may help explain previous mixed findings and
      advance implications for etiological models of psychopathy.

PMID- 24933284
TI  - Chemical analysis and antihyperglycemic activity of an original extract from
      burdock root (Arctium lappa).
AB  - In the present study, we obtained a dried burdock root extract (DBRE) rich in
      caffeoylquinic acids derivatives. We performed the chemical characterization of
      DBRE and explored its antihyperglycemic potential in both in vitro and in vivo
      experiments. Chemical analysis of DBRE using LC-MS and GC-MS revealed the
      presence of a great majority of dicaffeoylquinic acid derivatives (75.4%) of
      which 1,5-di-O-caffeoyl-4-O-maloylquinic acid represents 44% of the extract. In
      the in vitro experiments, DBRE is able to increase glucose uptake in cultured L6
      myocytes and to decrease glucagon-induced glucose output from rat isolated
      hepatocytes together with a reduction of hepatic glucose 6-phosphatase activity.
      DBRE did not increase insulin secretion in the INS-1 pancreatic beta-cell line.
      In vivo, DBRE improves glucose tolerance both after intraperitoneal and oral
      subchronic administration. In conclusion, our data demonstrate that DBRE
      constitutes an original set of caffeoylquinic acid derivatives displaying
      antihyperglycemic properties. 

PMID- 24933285
TI  - Ultrasound-accelerated versus standard catheter-directed thrombolysis in 102
      patients with acute and subacute limb ischemia.
AB  - PURPOSE: To compare the safety and efficacy of ultrasound-accelerated
      thrombolysis (UAT) and standard catheter-directed thrombolysis (CDT) in patients
      with acute and subacute limb ischemia. MATERIALS AND METHODS: Medical records of
      all patients treated with thrombolysis for acute and subacute limb ischemia
      between August 2005 and January 2012 were reviewed. Coprimary (increase in ankle
      brachial index, degree of lysis) and secondary endpoints (technical success,
      distal embolization, bleeding complications, need for additional interventions)
      were assessed. UAT was performed in 75 patients, and CDT was performed in 27
      patients. Patients' baseline demographic and clinical parameters and procedure
      details, including lytic drug infusion rate (P = .704 and P = .987), total
      infusion time (P = .787 and P = .377), and use of adjunctive procedures (P =
      .457), did not differ significantly between the two groups. RESULTS: Complete
      lysis was achieved in 72.0% (UAT) and 63.0% (CDT) of patients (P = .542);
      hemodynamic success was achieved in 91.8% (UAT) and 92.3% (CDT) (P = .956).
      Overall major and minor bleeding complications were observed in 6.9% (UAT) and
      3.9% (CDT) of patients. Major (P = .075) and minor (P = .276) bleeding
      independently did not differ between UAT and CDT. Major and minor bleeding
      combined was lower: 6.7% (UAT) versus 22.2% (CDT) (P = .025). Overall target
      vessel patency after 8.0 months (range, 1.5-20.5 mo) was 73.5%; target vessel
      patency for UAT was 75.9% versus 64.3% for CDT (P = .379). Median long-term
      survival was not significantly different between UAT and CDT: 3.6 years (range,
      2.42-5.33 y) versus 1.8 years (range, 1.33-4.92 y) (P = .061). CONCLUSIONS: Both
      UAT and CDT are safe and efficient treatment modalities for patients with acute
      and subacute limb ischemia. The observed lower risk of total bleeding for UAT
      versus CDT may warrant prospective comparative trials.

PMID- 24933286
TI  - Ethosuximide reduces electrographical and behavioral correlates of alcohol
      withdrawal seizure in DBA/2J mice.
AB  - Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound
      hyperexcitability can result in withdrawal seizure. Withdrawal symptoms,
      including seizures, may drive individuals to relapse, thus representing a
      significant barrier to recovery. Our lab previously identified an upregulation of
      the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor
      to the generation and propagation of seizures in a model of withdrawal. In the
      present study, we examined whether ethosuximide (ETX), a T-channel antagonist,
      could decrease the severity of ethanol withdrawal seizures by evaluating
      electrographical and behavioral correlates of seizure activity. DBA/2J mice were
      exposed to an intermittent ethanol exposure paradigm. Mice were treated with
      saline or ETX in each withdrawal period, and cortical EEG activity was recorded
      to determine seizure severity. We observed a progression in seizure activity with
      each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal
      induced spike and wave discharges (SWDs), in terms of absolute number, duration
      of events, and contribution to EEG power in the 6-10 Hz frequency range. We also
      evaluated the effects of ETX on handling-induced convulsions. Overall, we
      observed a decrease in handling-induced convulsion severity in mice treated with
      ETX. Our findings suggest that ETX may be a useful pharmacological agent for
      studies of alcohol withdrawal and treatment of resulting seizures.

PMID- 24933287
TI  - First llama (Lama glama) pregnancy obtained after in vitro fertilization and in
      vitro culture of gametes from live animals.
AB  - The aim of this study was to evaluate the developmental competence and pregnancy
      rate of llama hatched blastocysts produced in vitro using gametes from live
      animals and two different culture conditions. Fifteen adult females were
      superstimulated with 1500 IU of eCG, eleven (73%) responded to the treatment and
      were used as oocyte donors. Follicular aspiration was conducted by flank
      laparotomy. Semen collections were performed under general anesthesia by
      electroejaculation of the male. Sixty-six COCs were recovered from 77 aspirated
      follicles (86% recovery) and were randomly placed in Fertil-TALP microdroplets
      with the sperm suspension (20 * 10(6)live spermatozoa/ml). After 24 h, they were
      placed in SOFaa medium supplemented with FCS and randomly assigned to one of two
      culture conditions. Culture condition 1 (CC1) consisted of 6 days of culture
      (n=28) and culture condition 2 (CC2) consisted of renewing the culture medium
      every 48 h (n=35). In CC1, the blastocyst rate was 36% (10/28) and the hatched
      blastocyst rate was 28% (8/28) whereas in CC2, the blastocyst rate was 34%
      (12/35) and the hatched blastocyst rate was 20% (7/35) (p>0.05). No pregnancies
      were obtained after embryo transfer (ET) of CC1 blastocysts (0/8) while one
      pregnancy was obtained (1/7) after transferring a hatched blastocyst from CC2.
      Forty-two days after the ET, the pregnancy was lost. This study represents the
      first report of a pregnancy in the llama after intrauterine transfer of embryos
      produced by in vitro fertilization using gametes from live animals.

PMID- 24933288
TI  - Warm water bath stimulates phase-shifts of the peripheral circadian clocks in
      PER2::LUCIFERASE mouse.
AB  - Circadian clocks in the peripheral tissues of mice are known to be entrained by
      pulse stimuli such as restricted feeding, novel wheel running, and several other
      agents. However, there are no reports on high temperature pulse-mediated
      entrainment on the phase-shift of peripheral clocks in vivo. Here we show that
      temperature treatment of mice for two days at 41 degrees C, instead of 37 degrees
      C, for 1-2 h during the inactive period, using a temperature controlled water
      bath stimulated phase-advance of peripheral clocks in the kidney, liver, and
      submandibular gland of PER2::LUCIFERASE mice. On the other hand, treatment for 2
      days at 35 degrees C ambient room temperature for 2 h did not cause a phase
      advance. Maintenance of mice at 41 degrees C in a water bath, sustained the core
      body temperature at 40-41 degrees C. However, the use of 37 degrees C water bath
      or the 35 degrees C ambient room temperature elevated the core body temperature
      to 38.5 degrees C, suggesting that at least a core body temperature of 40-41
      degrees C is necessary to cause phase-advance under light-dark cycle conditions.
      The temperature pulse stimulation at 41 degrees C, instead of 37 degrees C water
      bath for 2 h led to the elevated expression of Per1 and Hsp70 in the peripheral
      tissue of mice. In summary, the present study demonstrates that transient high
      temperature pulse using water bath during daytime causes phase-advance in mouse
      peripheral clocks in vivo. The present results suggest that hot water bath may
      affect the phase of peripheral clocks. 

PMID- 24933289
TI  - Predictive DFT-based approaches to charge and spin transport in single-molecule
      junctions and two-dimensional materials: successes and challenges.
AB  - CONSPECTUS: The emerging field of flexible electronics based on organics and two
      dimensional (2D) materials relies on a fundamental understanding of charge and
      spin transport at the molecular and nanoscale. It is desirable to make
      predictions and shine light on unexplained experimental phenomena independently
      of experimentally derived parameters. Indeed, density functional theory (DFT),
      the workhorse of first-principles approaches, has been used extensively to model
      charge/spin transport at the nanoscale. However, DFT is essentially a ground
      state theory that simply guarantees correct total energies given the correct
      charge density, while charge/spin transport is a nonequilibrium phenomenon
      involving the scattering of quasiparticles. In this Account, we critically assess
      the validity and applicability of DFT to predict charge/spin transport at the
      nanoscale. We also describe a DFT-based approach, DFT+Sigma, which incorporates
      corrections to Kohn-Sham energy levels based on many-electron calculations. We
      focus on single-molecule junctions and then discuss how the important
      considerations for DFT descriptions of transport can differ in 2D materials. We
      conclude that when used appropriately, DFT and DFT-based approaches can play an
      important role in making predictions and gaining insight into transport in these
      materials. Specifically, we shall focus on the low-bias quasi-equilibrium regime,
      which is also experimentally most relevant for single-molecule junctions. The
      next question is how well can the scattering of DFT Kohn-Sham particles
      approximate the scattering of true quasiparticles in the junction? Quasiparticles
      are electrons (holes) that are surrounded by a constantly changing cloud of holes
      (electrons), but Kohn-Sham particles have no physical significance. However, Kohn
      Sham particles can often be used as a qualitative approximation to
      quasiparticles. The errors in standard DFT descriptions of transport arise
      primarily from errors in the Kohn-Sham energy levels (self-energy errors). These
      errors are small in the strong-coupling regime where the molecular levels are
      significantly broadened at the Fermi level but are large in the coherent off
      resonant tunneling regime where DFT overestimates conductance by orders of
      magnitude. The DFT+Sigma approach uses a physically motivated, parameter free
      estimate of the self-energy corrections to correct the energy levels in DFT,
      giving conductance in quantitative agreement with experiment for a large but
      nonexhaustive class of single-molecule junctions. In 2D materials, the self
      energy error is relatively small, and critical issues stem instead from the large
      length scales in experiments, which make it necessary to consider band-bending
      within the 2D material, as well as scattering due to electron-phonon
      interactions, spin-flip interactions, defects, etc.

PMID- 24933290
TI  - [Whipple's disease and Tropheryma whipplei infections in internal medicine. When
      to think about it? How to treat?].
AB  - Tropheryma whipplei culture and genome sequencing have, thanks to new tools,
      rationalized both diagnosis and treatment of Whipple's disease. Whipple's disease
      involves mainly Caucasian male, approximately 50-years-old, suffering from
      arthralgia, weight loss and diarrhea. A worsening of clinical manifestations
      after immunosuppressive therapy is frequently observed while antibiotics
      prescribed for another infection improves the clinical status. Clinical
      manifestations may more rarely suggest lymphoma or sarcoidosis. Positive T.
      whipplei performed on both saliva and stool samples are strongly suggestive of
      Whipple's disease. The diagnosis is confirmed by positive periodic acid Schiff
      staining or immunohistochemistry performed on small-bowel biopsies. Localized
      chronic infections are defined by the absence of histological duodenal
      involvement. Endocarditis mainly occurs in 60-years-old men with arthralgia,
      cardiac failure or embolic events. Encephalitis causes mainly cognitive and
      psychiatric involvement, and sometimes dementia, ataxia and weight gain. Uveitis
      and arthritis evolve chronically, and are frequently resistant to
      immunosuppressive treatment. PCR and culture (particularly for cerebrospinal
      fluid) performed on various tissues and fluids allow the localized infections
      diagnosis. In classic Whipple's disease, the treatment with doxycycline
      (200mg/day) and hydroxychloroquine (600 mg/day) for a length of 12 months
      followed by a lifetime treatment by doxycycline (200 mg/day) should be
      recommended to avoid reinfection. In localized infections, a treatment with
      doxycycline (200mg/day) and hydroxychloroquine (600 mg/day) is proposed for 12 to
      18 months followed by a lifetime follow-up.

PMID- 24933291
TI  - Bloodstream infection outbreaks related to opioid-diverting health care workers:
      a cost-benefit analysis of prevention and detection programs.

PMID- 24933293
TI  - Factors affecting circulating levels of peptide YY in humans: a comprehensive
      review.
AB  - As obesity continues to be a global epidemic, research into the mechanisms of
      hunger and satiety and how those signals act to regulate energy homeostasis
      persists. Peptide YY (PYY) is an acute satiety signal released upon nutrient
      ingestion and has been shown to decrease food intake when administered
      exogenously. More recently, investigators have studied how different factors
      influence PYY release and circulating levels in humans. Some of these factors
      include exercise, macronutrient composition of the diet, body-weight status,
      adiposity levels, sex, race and ageing. The present article provides a succinct
      and comprehensive review of the recent literature published on the different
      factors that influence PYY release and circulating levels in humans. Where human
      data are insufficient, evidence in animal or cell models is summarised.
      Additionally, the present review explores the recent findings on PYY responses to
      different dietary fatty acids and how this new line of research will make an
      impact on future studies on PYY. Human demographics, such as sex and age, do not
      appear to influence PYY levels. Conversely, adiposity or BMI, race and acute
      exercise all influence circulating PYY levels. Both dietary fat and protein
      strongly stimulate PYY release. Furthermore, MUFA appear to result in a smaller
      PYY response compared with SFA and PUFA. PYY levels appear to be affected by
      acute exercise, macronutrient composition, adiposity, race and the composition of
      fatty acids from dietary fat. 

PMID- 24933292
TI  - Outbreaks of infections associated with drug diversion by US health care
      personnel.
AB  - OBJECTIVE: To summarize available information about outbreaks of infections
      stemming from drug diversion in US health care settings and describe recommended
      protocols and public health actions. PATIENTS AND METHODS: We reviewed records at
      the Centers for Disease Control and Prevention related to outbreaks of infections
      from drug diversion by health care personnel in US health care settings from
      January 1, 2000, through December 31, 2013. Searches of the medical literature
      published during the same period were also conducted using PubMed. Information
      compiled included health care setting(s), infection type(s), specialty of the
      implicated health care professional, implicated medication(s), mechanism(s) of
      diversion, number of infected patients, number of patients with potential
      exposure to blood-borne pathogens, and resolution of the investigation. RESULTS:
      We identified 6 outbreaks over a 10-year period beginning in 2004; all occurred
      in hospital settings. Implicated health care professionals included 3 technicians
      and 3 nurses, one of whom was a nurse anesthetist. The mechanism by which
      infections were spread was tampering with injectable controlled substances. Two
      outbreaks involved tampering with opioids administered via patient-controlled
      analgesia pumps and resulted in gram-negative bacteremia in 34 patients. The
      remaining 4 outbreaks involved tampering with syringes or vials containing
      fentanyl; hepatitis C virus infection was transmitted to 84 patients. In each of
      these outbreaks, the implicated health care professional was infected with
      hepatitis C virus and served as the source; nearly 30,000 patients were
      potentially exposed to blood-borne pathogens and targeted for notification
      advising testing. CONCLUSION: These outbreaks revealed gaps in prevention,
      detection, and response to drug diversion in US health care facilities. Drug
      diversion is best prevented by health care facilities having strong narcotics
      security measures and active monitoring systems. Appropriate response includes
      assessment of harm to patients, consultation with public health officials when
      tampering with injectable medication is suspected, and prompt reporting to
      enforcement agencies.

PMID- 24933294
TI  - Estimating causal effects from multiple-baseline studies: implications for design
      and analysis.
AB  - Traditionally, average causal effects from multiple-baseline data are estimated
      by aggregating individual causal effect estimates obtained through within-series
      comparisons of treatment phase trajectories to baseline extrapolations. Concern
      that these estimates may be biased due to event effects, such as history and
      maturation, motivates our proposal of a between-series estimator that contrasts
      participants in the treatment to those in the baseline phase. Accuracy of the new
      method was assessed and compared in a series of simulation studies where
      participants were randomly assigned to intervention start points. The within
      series estimator was found to have greater power to detect treatment effects but
      also to be biased due to event effects, leading to faulty causal inferences. The
      between-series estimator remained unbiased and controlled the Type I error rate
      independent of event effects. Because the between-series estimator is unbiased
      under different assumptions, the 2 estimates complement each other, and the
      difference between them can be used to detect inaccuracies in the modeling
      assumptions. The power to detect inaccuracies associated with event effects was
      found to depend on the size and type of event effect. We empirically illustrate
      the methods using a real data set and then discuss implications for researchers
      planning multiple-baseline studies.

PMID- 24933296
TI  - Factors predicting an arrhythmogenic superior vena cava in atrial fibrillation
      ablation: insight into the mechanism.
AB  - BACKGROUND: The superior vena cava (SVC) is an infrequent but important source of
      atrial fibrillation (AF), but is not always easy to identify. OBJECTIVE: This
      study aimed to identify predictors of an arrhythmogenic SVC (a-SVC) in patients
      undergoing AF ablation. METHODS: Eight hundred thirty-six consecutive patients
      undergoing AF ablation were analyzed. All patients underwent pulmonary vein
      antrum isolation during the index procedure. An a-SVC, defined as SVC-triggered
      AF and an SVC associated with the maintenance of AF, was evaluated by mapping
      catheters throughout the procedure. RESULTS: An a-SVC was identified in 44
      patients (5.3%) during a total of 1063 procedures. Patients with an a-SVC were
      younger, less obese, and had a smaller left atrial (LA) size and more paroxysmal
      AF than those without an a-SVC. The presence of structural heart disease and
      hypertension was lower, and the coexistence of spontaneous common atrial flutter
      (AFL) before or during the index procedure was higher in those with an a-SVC than
      in those without. A multiple logistic regression analysis revealed that the LA
      size (odds ratio 0.93; 95% confidence interval 0.88-0.99; P = .038) and
      coexistence of spontaneous common AFL (odds ratio 2.01; 95% confidence interval
      1.00-4.02; P = .048) were independent predictors identifying an a-SVC. Although
      19 patients (43.2%) required repeat procedures, 39 (88.6%) were free from any
      atrial tachyarrhythmias without antiarrhythmic drugs at a median of 16.5 months
      (25th-75th percentiles 9.0-27.0 months) after a mean of 1.5 +/- 0.7 procedures.
      CONCLUSION: A smaller LA size and coexistence of spontaneous common AFL were
      independent predictors of an a-SVC in the context of AF ablation.

PMID- 24933298
TI  - Palliative care provision for patients with a hematological malignancy: can we do
      more?

PMID- 24933297
TI  - Lanthanide-doped upconversion nanoparticles electrostatically coupled with
      photosensitizers for near-infrared-triggered photodynamic therapy.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great
      promise in photodynamic therapy (PDT). Herein, we report a facile strategy to
      fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs
      coupled with a photosensitizer of a beta-carboxyphthalocyanine zinc (ZnPc-COOH)
      molecule via direct electrostatic interaction. Due to the close proximity between
      UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from
      UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet
      oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high
      efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth
      both in vitro and in vivo, thereby revealing the great potential of the UCNP
      based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer
      therapy. 

PMID- 24933299
TI  - Prophylactic antibiotics for preventing Gram-positive infections associated with
      long-term central venous catheters in oncology patients: beneficial or not?

PMID- 24933300
TI  - Rare combination of bilateral divided atrial chambers and pulmonary vein stenosis
      with review of the literature.
AB  - INTRODUCTION: The term cor triatriatum is used to describe a fibromuscular
      partition that divides an atrium into two compartments. It was first used by
      Borst in 1905, although the lesion had been described before by Church in 1868.
      Both described divided left atrial chamber (also referred to as cor triatriatum
      sinister). The incidence of the divided left atrial chamber among patients with
      congenital heart disease is reported at 0.1% and 0.4% in an autopsy study.
      Divided right atrial chamber - also referred to as cor triatriatum dexter - is
      even rarer to an extent that there is no reported incidence and only few hundred
      cases have been reported so far. A search through pubMed library revealed only 90
      publications on humans, either under the term "dexter" or "dextrum". We would
      like to report a new association of bilateral divided atrial chambers and
      pulmonary vein stenosis, with a review of the literature.

PMID- 24933301
TI  - The ghrelin-GHSR-1a system in the ocular neuro-humoral regulation. Pearls and
      controversies.

PMID- 24933302
TI  - Wolman's disease with secondary hemophagocytic lymphohistiocytosis.

PMID- 24933303
TI  - Hemolysin of enterohemorrhagic Escherichia coli: structure, transport, biological
      activity and putative role in virulence.
AB  - Enterohemorrhagic Escherichia coli (EHEC) cause diarrhea, bloody diarrhea and
      hemolytic-uremic syndrome (HUS), a thrombotic microangiopathy affecting the renal
      glomeruli, the intestine, and the brain. The pathogenesis of EHEC-mediated
      diseases is incompletely understood. In addition to Shiga toxins, the major
      virulence factors of EHEC, the contribution of EHEC hemolysin (EHEC-Hly), also
      designated EHEC toxin (Ehx), which is a member of the RTX (repeats-in-toxin)
      family, is increasingly recognized. The toxin and its activation and secretion
      machinery are encoded by the EHEC-hlyCABD operon, in which EHEC-hlyA is the
      structural gene for EHEC-Hly and the EHEC-hlyC product mediates post
      translational activation of EHEC-Hly; the EHEC-hlyB- and EHEC-hlyD-encoded
      proteins form, together with genetically unlinked TolC, the type I secretion
      system that transports EHEC-Hly out of the bacterial cell. EHEC-Hly exists in two
      biologically active forms: as a free EHEC-Hly, and an EHEC-Hly associated with
      outer membrane vesicles (OMVs) that are released by EHEC during growth. The OMV
      associated form results from a rapid binding of free EHEC-Hly to OMVs upon its
      extracellular secretion. The OMV association stabilizes EHEC-Hly and thus
      substantially prolongs its hemolytic activity compared to the free toxin. The two
      EHEC-Hly forms differ by their mechanism of toxicity toward human intestinal
      epithelial and microvascular endothelial cells, which are the major targets
      during EHEC infection. The free EHEC-Hly lyses human microvascular endothelial
      cells, presumably by pore formation in the cell membrane. In contrast, the OMV
      associated EHEC-Hly does not lyse any of these cell types, but after its cellular
      internalization via OMVs it targets mitochondria and triggers caspase-9-mediated
      apoptosis. The proinflammatory potential of EHEC-Hly, in particular its ability
      to elicit secretion of interleukin-1beta from human monocytes/macrophages, might
      be an additional mechanism of its putative contribution to the pathogenesis of
      EHEC-mediated diseases. Increasing understanding of molecular mechanisms
      underlying interaction of EHEC-Hly with target cells as well as the host cell
      responses to the toxin supports the involvement of EHEC-Hly in the pathogenesis
      of EHEC-mediated diseases and forms a basis for prevention of the EHEC-Hly
      mediated injury during human infection.

PMID- 24933304
TI  - Phenotypic and molecular characterization of hyperpigmented group B Streptococci.
AB  - Group B Streptococcus (GBS) causes invasive infections in neonates, older adults
      and patients with comorbidities. beta-hemolysin/cytolysin is an important GBS
      virulence factor. It is encoded by the cyl operon and confers GBS hemolytic
      activity. Isolates displaying hyperpigmentation are typically hyperhemolytic.
      Comparison of clonally identical isolates displaying different levels of
      pigmentation has shown transcriptional dysregulation due to mutations in
      components of the control of the virulence S/R (CovS/R) regulatory system. In
      addition, hyperpigmented isolates show decreased CAMP factor and decreased
      capsule thickness. In analogy to findings in group A Streptococcus, a pivotal
      role of CovS/R has been proposed in the host-pathogen interaction of invasive GBS
      infection. However, corresponding investigations on multiple clinical GBS
      isolates have not been performed. We prospectively collected hyperpigmented
      isolates found in a diagnostic laboratory and performed phenotypic, molecular and
      transcriptional analyses. In the period from 2008 to 2012, we found 10 isolates
      obtained from 10 patients. The isolates reflected both invasive pathogens and
      colonizers. In three cases, clonally identical but phenotypically different
      variants were also found. Hence, the analyses included 13 isolates. No capsular
      serotype was found to be significantly more frequent. Bacterial pigments were
      analyzed via spectrophotometry and for their hemolytic activity. Data obtained
      for typical absorbance spectra peaks correlated significantly with hemolytic
      activity. Molecular analysis of the cyl operon showed that it was conserved in
      all isolates. The covR sequence displayed mutations in five isolates; in one
      isolate, the CovR binding site to cylX was abrogated. Our results on clinical
      isolates support previous findings on CovR-deficient isogenic mutants, but
      suggest that - at least in some clinical isolates - for beta-hemolysin/cytolysin
      and CAMP factor production, other molecular pathways may be involved. 

PMID- 24933305
TI  - The use of cone beam computed tomography in the postoperative assessment of
      orbital wall fracture reconstruction.
AB  - PURPOSE: Computed tomography (CT) is currently the standard in postoperative
      evaluation of orbital wall fracture reconstruction, but cone beam computed
      tomography (CBCT) offers potential advantages including reduced radiation dose
      and cost. The purpose of this study is to examine objectively the image quality
      of CBCT in the postoperative evaluation of orbital fracture reconstruction, its
      radiation dose, and cost compared with CT. MATERIALS AND METHODS: Four
      consecutive patients with orbital wall fractures in whom surgery was indicated
      underwent orbital reconstruction with radio-opaque grafts (bone, titanium
      reinforced polyethylene, and titanium plate) and were assessed postoperatively
      with orbital CBCT. CBCT was evaluated for its ability to provide objective
      information regarding the adequacy of orbital reconstruction, radiation dose, and
      cost. RESULTS: In all patients, CBCT was feasible and provided hard tissue image
      quality comparable to CT with significantly reduced radiation dose and cost.
      However, it has poorer soft tissue resolution, which limits its ability to
      identify the extraocular muscles, their relationship to the reconstructive graft,
      and potential muscle entrapment. CONCLUSIONS: CBCT is a viable alternative to CT
      in the routine postoperative evaluation of orbital fracture reconstruction.
      However, in the patient who develops gaze restriction postoperatively,
      conventional CT is preferred over CBCT for its superior soft tissue resolution to
      exclude extraocular muscle entrapment.

PMID- 24933306
TI  - Giant epidermal inclusion cyst over the parotid gland mixing parotid tumor.

PMID- 24933307
TI  - Esthesioneuroblastoma of the parotid gland.

PMID- 24933308
TI  - Comparative study in orthognathic surgery between Dolphin Imaging software and
      manual prediction.

PMID- 24933310
TI  - Clinical-radiographic analysis of Eagle syndrome.

PMID- 24933311
TI  - J-bone graft for the reconstruction of the jaws.
AB  - The J-bone graft technique has been used for the reconstruction of glenoid
      surfaces with significant bone loss in orthopedic surgery in which the J-shaped
      bicortical bone graft is harvested from the iliac crest. Because of the osteotomy
      design, the press-fit fixation into the defect is obtained. In this technical
      note, the authors adopted this technique to oral and maxillofacial surgery and
      described the technique for the reconstruction of the jaws. 

PMID- 24933312
TI  - Mean platelet volume may not be beneficial for the management of patients with
      adenoid hypertrophy.

PMID- 24933313
TI  - Why platelet-rich plasma failed to promote bone healing in combination with a
      biphasic synthetic graft material in bone defects: a critical comment.

PMID- 24933314
TI  - Vertebral artery stenosis is a very unlikely cause of Horner syndrome.

PMID- 24933315
TI  - Preferential adsorption from liquid water-ethanol mixtures in alumina pores.
AB  - The sorptivity, structure, and dynamics of liquid water-ethanol mixtures confined
      in alumina pores were studied by molecular dynamics simulations. Due to an
      effective stronger attraction between water and the alumina surface, our
      simulations show that water is preferentially adsorbed in alumina nanopores from
      bulk solutions of varying composition. These results are in good qualitative
      agreement with experimental data reported by Rao and Sircar (Adsorpt. Sci.
      Technol. 1993, 10, 93). Analysis of the simulated trajectories allows us to
      predict that water diffuses through the narrow pores more easily than ethanol, in
      part because of its smaller size. Our results suggest that ethanol has an
      antiplasticization effect on water within the narrow pores considered here,
      whereas it has a plasticization effect on water in the bulk. Rao and Sircar
      suggested that alumina could be used in concentration swing and/or concentration
      thermal swing adsorption processes to separate water from ethanol. In addition,
      our results suggest the possibility of using alumina for manufacturing
      permselective membranes to produce anhydrous ethanol from liquid water-ethanol
      solutions. 

PMID- 24933316
TI  - Comparison of 3D dose distributions for HDR 192Ir brachytherapy sources with
      normoxic polymer gel dosimetry and treatment planning system.
AB  - Radiation fluence changes caused by the dosimeter itself and poor spatial
      resolution may lead to lack of 3-dimensional (3D) information depending on the
      features of the dosimeter and quality assurance of dose distributions for high
      dose rate (HDR) iridium-192 ((192)Ir) brachytherapy sources is challenging and
      experimental dosimetry methods used for brachytherapy sources are limited. In
      this study, we investigated 3D dose distributions of (192)Ir brachytherapy
      sources for irradiation with single and multiple dwell positions using a normoxic
      gel dosimeter and compared them with treatment planning system (TPS)
      calculations. For dose calibration purposes, 100-mL gel-containing vials were
      irradiated at predefined doses and then scanned in an magnetic resonance (MR)
      imaging unit. Gel phantoms prepared in 2 spherical glasses were irradiated with
      (192)Ir for the calculated dwell positions, and MR scans of the phantoms were
      obtained. The images were analyzed with MATLAB software. Dose distributions and
      profiles derived with 1-mm resolution were compared with TPS calculations.
      Linearity was observed between the delivered dose and the reciprocal of the T2
      relaxation time constant of the gel. The x-, y-, and z-axes were defined as the
      sagittal, coronal, and axial planes, respectively, the sagittal and axial planes
      were defined parallel to the long axis of the source while the coronal plane was
      defined horizontally to the long axis of the source. The differences between
      measured and calculated profile widths of 3-cm source length and point source for
      70%, 50%, and 30% isodose lines were evaluated at 3 dose levels using 18 profiles
      of comparison. The calculations for 3-cm source length revealed a difference of >
      3mm in 1 coordinate at 50% profile width on the sagittal plane and 3 coordinates
      at 70% profile width and 2 coordinates at 50% and 30% profile widths on the axial
      plane. Calculations on the coronal plane for 3-cm source length showed > 3-mm
      difference in 1 coordinate at 50% and 70% and 2 coordinates at 30% profile
      widths. The point source measurements and calculations for 50% profile widths
      revealed a difference > 3mm in 1 coordinate on the sagittal plane and 2
      coordinates on the axial plane. The doses of 3 coordinates on the sagittal plane
      and 4 coordinates on the axial plane could not be evaluated in 30% profile width
      because of low doses. There was good agreement between the gel dosimetry and TPS
      results. Gel dosimetry provides dose distributions in all 3 planes at the same
      time, which enables us to define the dose distributions in any plane with high
      resolution. It can be used to obtain 3D dose distributions for HDR (192)Ir
      brachytherapy sources and 3D dose verification of TPS. 

PMID- 24933317
TI  - A class solution for volumetric-modulated arc therapy planning in
      postprostatectomy radiotherapy.
AB  - This study is aimed to test a postprostatectomy volumetric-modulated arc therapy
      (VMAT) planning class solution. The solution applies to both the progressive
      resolution optimizer algorithm version 2 (PRO 2) and the algorithm version 3 (PRO
      3), addressing the effect of an upgraded algorithm. A total of 10 radical
      postprostatectomy patients received 68 Gy to 95% of the planning target volume
      (PTV), which was planned using VMAT. Each case followed a set of planning
      instructions; including contouring, field setup, and predetermined optimization
      parameters. Each case was run through both algorithms only once, with no user
      interaction. Results were averaged and compared against Radiation Therapy
      Oncology Group (RTOG) 0534 end points. In addition, the clinical target volume
      (CTV) D100, PTV D99, and PTV mean doses were recorded, along with conformity
      indices (CIs) (95% and 98%) and the homogeneity index. All cases satisfied PTV
      D95 of 68 Gy and a maximum dose < 74.8 Gy. The average result for the PTV D99 was
      64.1 Gy for PRO 2 and 62.1 Gy for PRO 3. The average PTV mean dose for PRO 2 was
      71.4 Gy and 71.5 Gy for PRO 3. The CTV D100 average dose was 67.7 and 68.0 Gy for
      PRO 2 and PRO 3, respectively. The mean homogeneity index for both algorithms was
      0.08. The average 95% CI was 1.17 for PRO 2 and 1.19 for PRO 3. For 98%, the
      average results were 1.08 and 1.12 for PRO 2 and PRO 3, respectively. All cases
      for each algorithm met the RTOG organs at risk dose constraints. A successful
      class solution has been established for prostate bed VMAT radiotherapy regardless
      of the algorithm used.

PMID- 24933318
TI  - Crossover experiments applied to network formation reactions: improved strategies
      for counting elastically inactive molecular defects in PEG gels and hyperbranched
      polymers.
AB  - Molecular defects critically impact the properties of materials. Here we
      introduce a paradigm called "isotopic labeling disassembly spectrometry" (ILDaS)
      that facilitates unprecedented precise experimental correlations between
      elastically inactive network defects (dangling chains and primary loops) and
      network formation kinetics and precursor structure. ILDaS is inspired by
      classical crossover experiments, which are often used to interrogate whether a
      reaction mechanism proceeds via an inter- or intramolecular pathway. We show that
      if networks are designed from labeled bifunctional monomers that transfer their
      labels to multifunctional junctions upon network formation, then the extent of
      junction labeling correlates directly with the number of dangling chains and
      cyclic imperfections within the network. We demonstrate two complementary ILDaS
      approaches that enable defect measurements with short analysis times, low cost,
      and synthetic versatility applicable to a broad range of network materials
      including polydisperse polymer precursors. The results will spur new experimental
      and theoretical investigations into the interplay between polymer network
      structure and properties. 

PMID- 24933319
TI  - Trichomide A, a natural cyclodepsipeptide, exerts immunosuppressive activity
      against activated T lymphocytes by upregulating SHP2 activation to overcome
      contact dermatitis.
AB  - Increasing numbers of people are suffering from allergic contact dermatitis.
      However, the immunosuppressive drug candidate with negligible toxicity is still
      deficient. In the present study, we identified a natural cyclodepsipeptide named
      trichomide A that effectively inhibited the proliferation of activated T cells
      and reduced the production of proinflammatory cytokines but had almost no toxic
      effect on naive T cells at 0.3-3 MUM. In addition, trichomide A caused G0/G1
      phase arrest, suppressed the activation of AKT and STAT3, and increased the level
      of phosphorylated SHP2 in activated T cells in dose- and time-dependent manners.
      Furthermore, an in vivo experiment demonstrated that trichomide A significantly
      ameliorated picryl chloride (PCI)-induced contact hypersensitivity in mice. Such
      effects of trichomide A in the aforementioned experiments were significantly
      reversed by the inhibition of SHP2 activity using the SHP2-specific inhibitor
      PHPS1 or conditional SHP2 knockout mice in T cells, suggesting the SHP2-dependent
      action of trichomide A. Taken together, trichomide A showed an immunosuppressive
      activity against T cell-mediated immune responses both in vitro and in vivo,
      which has potential for the treatment of immune-related skin diseases.

PMID- 24933321
TI  - DC-HIL+ CD14+ HLA-DR no/low cells are a potential blood marker and therapeutic
      target for melanoma.

PMID- 24933320
TI  - Abnormally differentiating keratinocytes in the epidermis of systemic sclerosis
      patients show enhanced secretion of CCN2 and S100A9.
AB  - Skin involvement with dermal fibrosis is a hallmark of systemic sclerosis (SSc),
      and keratinocytes may be critical regulators of fibroblast function through
      secretion of chemo-attracting agents, as well as through growth factors and
      cytokines influencing the phenotype and proliferation rate of fibroblasts.
      Epithelial-fibroblast interactions have an important role in fibrosis in general.
      We have characterized the SSc epidermis and asked whether SSc-injured epidermal
      cells release factors capable of promoting fibrosis. Our results show that the
      SSc epidermis is hypertrophic, and has altered expression of terminal
      differentiation markers involucrin, loricrin, and filaggrin. Multiplex profiling
      revealed that SSc epidermal explants release increased levels of CCN2 and S100A9.
      CCN2 induction was found to spread into the upper papillary dermis, whereas
      S100A9 was shown to induce fibroblast proliferation and to enhance fibroblast
      CCN2 expression via Toll-like receptor 4. These data suggest that the SSc
      epidermis provides an important source of pro-fibrotic CCN2 and proinflammatory
      S100A9 in SSc skin, and therefore contributes to the fibrosis and inflammation
      seen in the disease. 

PMID- 24933322
TI  - Eating 'attentively' reduces later energy consumption in overweight and obese
      females.
AB  - Attentional and memory processes underpin appetite control, but whether
      encouraging overweight individuals to eat more 'attentively' can promote
      reductions in energy consumption is unclear. In the present study with a between
      subjects design, a total of forty-eight overweight and obese females consumed a
      fixed lunchtime meal. Their ad libitum energy intake of high-energy snack food
      was observed during a second laboratory session that occurred later that day. In
      the focused-attention condition, participants ate their lunch while listening to
      audio instructions that encouraged them to pay attention to the food being eaten.
      In a control condition, participants ate while listening to an audio book with a
      neutral (non-food-related) content. To test whether focused attention influenced
      food intake via enhancing the memory of the earlier consumed meal, we measured
      the participants' memory of their lunchtime meal. Ad libitum snack intake was
      approximately 30 % lower for participants in the focused-attention condition than
      for those in the control condition, and this difference was statistically
      significant. There was limited evidence that attention decreased later food
      intake by enhancing memory representation of the earlier consumed meal. Eating
      attentively can lead to a substantial decrease in later energy intake in
      overweight and obese individuals. Behavioural strategies that encourage a more
      'attentive' way of eating could promote sustained reductions in energy intake and
      weight loss.

PMID- 24933323
TI  - Exploring the role of conformational heterogeneity in cis-autoproteolytic
      activation of ThnT.
AB  - In the past decade, there have been major achievements in understanding the
      relationship between enzyme catalysis and protein structural plasticity. In
      autoprocessing systems, however, there is a sparsity of direct evidence of the
      role of conformational dynamics, which are complicated by their intrinsic
      chemical reactivity. ThnT is an autoproteolytically activated enzyme involved in
      the biosynthesis of the beta-lactam antibiotic thienamycin. Conservative mutation
      of ThnT results in multiple conformational states that can be observed via X-ray
      crystallography, establishing ThnT as a representative and revealing system for
      studing how conformational dynamics control autoactivation at a molecular level.
      Removal of the nucleophile by mutation to Ala disrupts the population of a
      reactive state and causes widespread structural changes from a conformation that
      promotes autoproteolysis to one associated with substrate catalysis. Finer
      probing of the active site polysterism was achieved by EtHg derivatization of the
      nucleophile, which indicates the active site and a neighboring loop have coupled
      dynamics. Disruption of these interactions by mutagenesis precludes the ability
      to observe a reactive state through X-ray crystallography, and application of
      this insight to other autoproteolytically activated enzymes offers an explanation
      for the widespread crystallization of inactive states. We suggest that the N
      >O(S) acyl shift in cis-autoproteolysis might occur through a si-face attack,
      thereby unifying the fundamental chemistry of these enzymes through a common
      mechanism.

PMID- 24933325
TI  - Acute dim light at night increases body mass, alters metabolism, and shifts core
      body temperature circadian rhythms.
AB  - The circadian system is primarily entrained by the ambient light environment and
      is fundamentally linked to metabolism. Mounting evidence suggests a causal
      relationship among aberrant light exposure, shift work, and metabolic disease.
      Previous research has demonstrated deleterious metabolic phenotypes elicited by
      chronic (>4 weeks) exposure to dim light at night (DLAN) (~ 5 lux). However, the
      metabolic effects of short-term (<2 weeks) exposure to DLAN are unspecified. We
      hypothesized that metabolic alterations would arise in response to just 2 weeks
      of DLAN. Specifically, we predicted that mice exposed to dim light would gain
      more body mass, alter whole body metabolism, and display altered body temperature
      (Tb) and activity rhythms compared to mice maintained in dark nights. Our data
      largely support these predictions; DLAN mice gained significantly more mass,
      reduced whole body energy expenditure, increased carbohydrate over fat oxidation,
      and altered temperature circadian rhythms. Importantly, these alterations
      occurred despite similar activity locomotor levels (and rhythms) and total food
      intake between groups. Peripheral clocks are potently entrained by body
      temperature rhythms, and the deregulation of body temperature we observed may
      contribute to metabolic problems due to "internal desynchrony" between the
      central circadian oscillator and temperature sensitive peripheral clocks. We
      conclude that even relatively short-term exposure to low levels of nighttime
      light can influence metabolism to increase mass gain.

PMID- 24933324
TI  - Daily rhythms are retained both in spontaneously developed sarcomas and in
      xenografts grown in immunocompromised SCID mice.
AB  - The circadian clock generates and regulates many daily physiological, metabolic
      and behavioral rhythms as well as acute responses to various types of stresses
      including those induced by anticancer treatment. It has been proposed that
      modulatory function of the clock may be used for improving the therapeutic
      efficacy of established anti-cancer treatments. In order to rationally exploit
      this mechanism, more information is needed to fully characterize the functional
      status of the molecular clock in tumors of different cellular origin; however,
      the data describing tumor clocks are still inconsistent. Here we tested the
      status of clock in two models of tumors derived from connective tissue: sarcomas
      spontaneously developed in p53-deficient mice and human fibrosarcoma cells grown
      as xenografts in immunocompromised severe combined immunodeficient (SCID) mice.
      We show that both types of tumors retain a functional clock, which is
      synchronized in phase with normal tissues. We also show that spontaneously
      developed tumors are not only oscillating in the context of an organism where
      they receive hormonal and metabolic signals but continue oscillating ex vivo in
      tissue explants demonstrating that tumors have functional clocks capable of
      timing all their functions. We also provide evidence that similar to liver,
      tumors can be synchronized by food availability independent of the central
      pacemaker in the suprachiasmatic nuclei (SCN). These data provide the basis for
      the design of anticancer therapies that take into account the circadian metabolic
      and physiological patterns of both the tumor and normal tissues. 

PMID- 24933326
TI  - To move or not to move: subthalamic deep brain stimulation effects on implicit
      motor simulation.
AB  - We explored implicit motor simulation processes in Parkinson's Disease (PD)
      patients with ON-OFF subthalamic deep brain stimulation (DBS) of the sub-thalamic
      nucleus (STN). Participants made lexical decisions about hand action-related
      verbs, abstract verbs, and pseudowords presented either within a positive (e.g.,
      "Do ...") or a negative (e.g., "Don't ...") sentence context. Healthy controls
      showed significantly slower responses for hand-action verbs (vs. abstract verbs)
      in the negative (vs. positive) context, which suggests that negative contexts may
      suppress motor simulation or preparation processes. The STN-DBS improves cortical
      motor functions, thus patients are expected to perform at the same level as
      unimpaired subjects in the ON condition. By contrast, the 50% reduced DBS is
      expected to result in a reduced activation for motor information, which in turn
      might cause a reduced, if not absent, context modulation. PD patients exhibited
      the same pattern as controls when their DBS was at 100% ON; however, reducing the
      DBS to 50% had a deleterious outcome on the positive faster than negative context
      effect, suggesting that the altered inhibition mechanism in PD could be
      responsible for the missed effect. In addition, our results confirm the view that
      implicit motor simulation mechanisms behind action-related verb processing are
      flexible and context-dependent. 

PMID- 24933328
TI  - Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to
      cardiac vagal neurons in the nucleus ambiguus.
AB  - Dexmedetomidine, an alpha2 adrenergic agonist, is a useful sedative but can also
      cause significant bradycardia. This decrease in heart rate may be due to
      decreased central sympathetic output as well as increased parasympathetic output
      from brainstem cardiac vagal neurons. In this study, using whole cell voltage
      clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and
      inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac
      vagal neurons in the rat nucleus ambiguus was determined. The results indicate
      that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to
      cardiac vagal neurons, with no significant effect on excitatory input. These
      results provide a mechanism for dexmedetomidine induced bradycardia and has
      implications for the management of this potentially harmful side effect. 

PMID- 24933327
TI  - Selective vasopressin-1a receptor antagonist prevents brain edema, reduces
      astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic
      brain injury.
AB  - A secondary and often lethal consequence of traumatic brain injury is cellular
      edema that we posit is due to astrocytic swelling caused by transmembrane water
      fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested
      whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4,
      reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR
      inhibition by SR49059 significantly reduced brain edema after cortical contusion
      injury (CCI) in rat 5h post-injury. Injured-hemisphere brain water content (n=6
      animals/group) and astrocytic area (n=3/group) were significantly higher in CCI
      vehicle (80.5+/-0.3%; 18.0+/-1.4 um(2)) versus sham groups (78.3+/-0.1%; 9.5+/
      0.9 um(2)), and SR49059 blunted CCI-induced increases in brain edema (79.0+/
      0.2%; 9.4+/-0.8um(2)). CCI significantly up-regulated GFAP, V1aR and AQP4 protein
      levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI
      vehicle, sham and CCI-SR49059 groups, GFAP was 1.58+/-0.04, 0.47+/-0.02, and
      0.81+/-0.03, respectively; V1aR was 1.00+/-0.06, 0.45+/-0.05, and 0.46+/-0.09;
      and AQP4 was 2.03+/-0.34, 0.49+/-0.04, and 0.92+/-0.22. Confocal
      immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059
      groups, fluorescence intensity of GFAP was 349+/-38, 56+/-5, and 244+/-30,
      respectively, V1aR was 601+/-71, 117.8+/-14, and 390+/-76, and AQP4 was 818+/
      117, 158+/-5, and 458+/-55 (n=3/group). The results support that edema was
      predominantly cellular following CCI and documented that V1aR inhibition with
      SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting
      edematous changes. Our findings suggest V1aR inhibitors may be potential
      therapeutic tools to prevent cellular swelling and provide treatment for post
      traumatic brain edema.

PMID- 24933330
TI  - Determination of liver specific toxicities in rat hepatocytes by high content
      imaging during 2-week multiple treatment.
AB  - DILI is a major safety issue during drug development and one of the leading
      causes for market withdrawal. Despite many efforts made in the past, the
      prediction of DILI using in vitro models remains very unreliable. In the present
      study, the well-established hepatocyte Collagen I-MatrigelTM sandwich culture was
      used, mimicking chronic drug treatment after multiple incubations for 14 days.
      Ten drugs associated with different types of specific preclinical and clinical
      liver injury were evaluated at non-cytotoxic concentrations. Mrp2-mediated
      transport, intracellular accumulation of neutral lipids and phospholipids were
      selected as functional endpoints by using CellomicsTM Arrayscan(r) technology and
      assessed at five timepoints (day 1, 3, 7, 10, 14). Liver specific functional
      impairments after drug treatment were enhanced over time and could be monitored
      by HCI already after few days and before cytotoxicity. Phospholipidosis-inducing
      drugs Chlorpromazine and Amiodarone displayed the same response as in vivo.
      Cyclosporin A, Chlorpromazine, and Troglitazone inhibited Mrp2-mediated biliary
      transport, correlating with in vivo findings. Steatosis remained difficult to be
      reproduced under the current in vitro testing conditions, resulting into false
      negative and positive responses. The present results suggest that the repeated
      long-term treatment of rat hepatocytes in the Collagen I-MatrigelTM sandwich
      configuration might be a suitable tool for safety profiling of the potential to
      induce phospholipidosis and impair Mrp2-mediated transport processes, but not to
      predict steatosis.

PMID- 24933331
TI  - A REVELation in non-small-cell lung cancer treatment?

PMID- 24933332
TI  - Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line
      treatment of stage IV non-small-cell lung cancer after disease progression on
      platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3
      trial.
AB  - BACKGROUND: Ramucirumab is a human IgG1 monoclonal antibody that targets the
      extracellular domain of VEGFR-2. We aimed to assess efficacy and safety of
      treatment with docetaxel plus ramucirumab or placebo as second-line treatment for
      patients with stage IV non-small-cell-lung cancer (NSCLC) after platinum-based
      therapy. METHODS: In this multicentre, double-blind, randomised phase 3 trial
      (REVEL), we enrolled patients with squamous or non-squamous NSCLC who had
      progressed during or after a first-line platinum-based chemotherapy regimen.
      Patients were randomly allocated (1:1) with a centralised, interactive voice
      response system (stratified by sex, region, performance status, and previous
      maintenance therapy [yes vs no]) to receive docetaxel 75 mg/m(2) and either
      ramucirumab (10 mg/kg) or placebo on day 1 of a 21 day cycle until disease
      progression, unacceptable toxicity, withdrawal, or death. The primary endpoint
      was overall survival in all patients allocated to treatment. We assessed adverse
      events according to treatment received. This study is registered with
      ClinicalTrials.gov, number NCT01168973. FINDINGS: Between Dec 3, 2010, and Jan
      24, 2013, we screened 1825 patients, of whom 1253 patients were randomly
      allocated to treatment. Median overall survival was 10.5 months (IQR 5.1-21.2)
      for 628 patients allocated ramucirumab plus docetaxel and 9.1 months (4.2-18.0)
      for 625 patients who received placebo plus docetaxel (hazard ratio 0.86, 95% CI
      0.75-0.98; p=0.023). Median progression-free survival was 4.5 months (IQR 2.3
      8.3) for the ramucirumab group compared with 3.0 months (1.4-6.9) for the control
      group (0.76, 0.68-0.86; p<0.0001). We noted treatment-emergent adverse events in
      613 (98%) of 627 patients in the ramucirumab safety population and 594 (95%) of
      618 patients in the control safety population. The most common grade 3 or worse
      adverse events were neutropenia (306 patients [49%] in the ramucirumab group vs
      246 [40%] in the control group), febrile neutropenia (100 [16%] vs 62 [10%]),
      fatigue (88 [14%] vs 65 [10%]), leucopenia (86 [14%] vs 77 [12%]), and
      hypertension (35 [6%] vs 13 [2%]). The numbers of deaths from adverse events (31
      [5%] vs 35 [6%]) and grade 3 or worse pulmonary haemorrhage (eight [1%] vs eight
      [1%]) did not differ between groups. Toxicities were manageable with appropriate
      dose reductions and supportive care. INTERPRETATION: Ramucirumab plus docetaxel
      improves survival as second-line treatment of patients with stage IV NSCLC.
      FUNDING: Eli Lilly.

PMID- 24933333
TI  - Different effects of bifeprunox, aripiprazole, and haloperidol on body weight
      gain, food and water intake, and locomotor activity in rats.
AB  - Following on the success of Aripiprazole with its high clinical efficacy and
      minimal side effects, further antipsychotic drugs (such as Bifeprunox) have been
      developed based on the same dopamine D2 partial agonist pharmacological profile
      as Aripiprazole. However clinical trials of Bifeprunox have found differing
      results to that of its predecessor, without the same significant clinical
      efficacy. This study has therefore investigated the different effects of 10 week
      treatment with Aripiprazole (0.75 mg/kg, 3 times per day), Bifeprunox (0.8 mg/kg,
      3 times per day) and Haloperidol (0.1mg/kg, 3 times per day) on body weight gain,
      food and water intake, white fat mass, and 8 week treatment on locomotor
      activity. Treatment with Bifeprunox was found to significantly reduce all of the
      measured parameters except white fat mass compared to the control group. However,
      Aripiprazole and Haloperidol treatment reduced water intake compared to the
      control, without any significant effects on the other measured parameters. These
      findings further demonstrate the potential pharmacological differences between
      Aripiprazole and Bifeprunox, and identify potential weight loss side effects and
      increased anxiety behaviour with Bifeprunox treatment.

PMID- 24933334
TI  - Augmentation of antidepressant effects of duloxetine and bupropion by caffeine in
      mice.
AB  - There is an unmet need in the treatment of depression suggesting requirement of
      new therapeutic approaches having better efficacy and safety profile. Patients
      receiving antidepressant therapy generally consume caffeine in the form of tea or
      coffee. The objective of the present study was to evaluate the augmentation of
      antidepressant effects of duloxetine and/or bupropion with caffeine. Male Swiss
      Albino mice received treatment of normal saline (10 ml/kg), 'caffeine alone'
      (10mg/kg), 'duloxetine alone' (10mg/kg), 'bupropion alone' (10mg/kg),
      caffeine+duloxetine (5mg/kg, each), bupropion+caffeine (5mg/kg, each), and
      bupropion+duloxetine (5mg/kg, each) through the intra-peritoneal route. The
      immobility period was analyzed 30 min after the treatment in forced swim and tail
      suspension tests. Norepinephrine, dopamine, and serotonin levels were analyzed in
      hippocampus, cerebral cortex and whole brain using HPLC with fluorescence
      detector. Euthanasia was performed 1h after treatment. Comparison between vehicle
      treated group and other groups showed significant decrease in immobility in all
      drug treated groups in both antidepressant models. Caffeine plus duloxetine
      treated group was better among the combination treated groups in terms of
      decrease in immobility and increase in norepinephrine, dopamine, and serotonin
      levels in hippocampi, cerebral cortices, and whole brain when compared to their
      respective monotherapy treated groups. These combination approaches may help in
      reducing the dose of duloxetine/bupropion, and consequently lower the associated
      side/adverse effects.

PMID- 24933335
TI  - Using the five-choice serial reaction time task to examine the effects of
      atomoxetine and methylphenidate in the male spontaneously hypertensive rat.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most common
      neurodevelopmental disorder and is normally treated with either stimulant or non
      stimulant medication such as methylphenidate and atomoxetine respectively. The
      impact of these drugs on attention and impulsivity has been explored extensively
      in healthy animals but there is little research into their effects in an animal
      model of ADHD. In the present study we investigated the effects of both drugs on
      the spontaneously hypertensive rat (SHR) model of ADHD using the five-choice
      serial reaction time task (5CSRTT). We found a number of difficulties associated
      with training this vulnerable strain on such a complex task. However, where rats
      were able to learn the task we found very small effects of methylphenidate;
      increased incorrect responding and therefore decreased accuracy, a marker of
      attention at a single dose. There were no significant effects of atomoxetine on
      accuracy once multiple comparisons were taken into consideration. We found no
      effects of either drug on premature responding, a marker of impulsivity. These
      results indicate that the 5CSRTT may not be most sensitive to the impulsivity
      displayed in the SHR. Furthermore, they suggest that the SHR may lack predictive
      validity and further investigation is needed to optimise use of this model. 

PMID- 24933336
TI  - High-dose corticosterone after fear conditioning selectively suppresses fear
      renewal by reducing anxiety-like response.
AB  - Exposure therapy is widely used to treat anxiety disorders, including
      posttraumatic stress disorder (PTSD). However, preventing the return of fear is
      still a major challenge after this behavioral treatment. An increasing number of
      studies suggest that high-dose glucocorticoid treatment immediately after trauma
      can alleviate the symptoms of PTSD in humans. Unknown is whether high-dose
      glucocorticoid treatment following fear conditioning suppresses the return of
      fear. In the present study, a typical fear renewal paradigm (AAB) was used, in
      which the fear response to an auditory cue can be restored in a novel context
      (context B) when both training and extinction occur in the same context (context
      A). We trained rats for auditory fear conditioning and administered
      corticosterone (CORT; 5 and 25mg/kg, i.p.) or vehicle with different delays (1
      and 24h). Forty-eight hours after drug injection, extinction was conducted with
      no drug in the training context, followed by a test of tone-induced freezing
      behavior in the same (AAA) or a shifted (AAB) context. Both immediate and delayed
      administration of high-dose CORT after fear conditioning reduced fear renewal. To
      examine the anxiolytic effect of CORT, independent rats were trained for cued or
      contextual fear conditioning, followed by an injection of CORT (5 and 25mg/kg,
      i.p.) or vehicle at a 1 or 24h delay. One week later, anxiety-like behavior was
      assessed in the elevated plus maze (EPM) before and after fear expression. We
      found that high-dose CORT decreased anxiety-like behavior without changing tone-
      or context-induced freezing. These findings indicate that a single high-dose CORT
      administration given after fear conditioning may selectively suppress fear
      renewal by reducing anxiety-like behavior and not by altering the consolidation,
      retrieval, or extinction of fear memory. 

PMID- 24933337
TI  - The effects of the estrus cycle and citalopram on anxiety-like behaviors and c
      fos expression in rats.
AB  - In rats, hormonal fluctuations during the estrus cycle may have numerous
      behavioral and neurobiological consequences. The aim of this study was to
      investigate the effects of estrus cycles and citalopram on behavior, ultrasonic
      vocalizations, anxiety levels, and c-fos expression in rats. With this aim, the
      rats were grouped into two: (1) a control group (n=16) and (2) a citalopram group
      (n=16), which received daily intraperitoneal 20mg/kg citalopram from baseline
      (D0) to the 10th day (D10). Behavioral analysis and ultrasonic vocalization (USV)
      recordings were made on D0 and D10. Next, the rats were further subgrouped
      according to estrus phases identified through a vaginal smear (8 proestrus rats
      and 8 non-proestrus rats, in each group). The rat's anxiety levels were analyzed
      with an elevated plus maze (EPM), and their c-fos expression was measured at the
      cingulate cortex, the amygdala, and the paraventricular thalamic nucleus. Our
      results showed that the citalopram group showed significantly more grooming
      behaviors on D10 than the control group (p=0.002). USVs on D0, D10 and during the
      EPM did not show any significant differences between the groups. Proestrus rats
      in the control group showed significantly less anxiety-like behavior during the
      EPM than the non-proestrus rats in the control group (p=0.028 for time spent in
      open arms, and p=0.011 for entries into open arms). There was no significant
      difference in anxiety-like behavior between the control and citalopram groups,
      and between the proestrus and non-estrous rats in the citalopram group. C-fos
      expression at the amygdala (p=0.013) and the paraventricular thalamic nucleus
      (p=0.014) was significantly inhibited in the citalopram group. We concluded that
      estrus cycles have a significant effect on anxiety levels in rats, which may be
      suppressed behaviorally and neurobiologically by citalopram. 

PMID- 24933338
TI  - A viscoelastic poromechanical model of the knee joint in large compression.
AB  - The elastic response of the knee joint in various loading and pathological
      conditions has been investigated using anatomically accurate geometry. However,
      it is still challenging to predict the poromechanical response of the knee in
      realistic loading conditions. In the present study, a viscoelastic,
      poromechanical model of the knee joint was developed for soft tissues undergoing
      large deformation. Cartilages and menisci were modeled as fibril-reinforced
      porous materials and ligaments were considered as fibril-reinforced hyperelastic
      solids. Quasi-linear viscoelasticty was formulated for the collagen network of
      these tissues and nearly incompressible Neo-Hookean hyperelasticity was used for
      the non-fibrillar matrix. The constitutive model was coded with a user defined
      FORTRAN subroutine, in order to use ABAQUS for the finite element analysis. Creep
      and stress relaxation were investigated with large compression of the knee in
      full extension. The contact pressure distributions were found similar in creep
      and stress relaxation. However, the load transfer in the joint was completely
      different in these two loading scenarios. During creep, the contact pressure
      between cartilages decreased but the pressure between cartilage and meniscus
      increased with time. This led to a gradual transfer of some loading from the
      central part of cartilages to menisci. During stress relaxation, however, both
      contact pressures decreased monotonically. 

PMID- 24933339
TI  - Dosimetric comparison of (192)Ir high-dose-rate brachytherapy vs. 50 kV x-rays as
      techniques for breast intraoperative radiation therapy: conceptual development of
      image-guided intraoperative brachytherapy using a multilumen balloon applicator
      and in-room CT imaging.
AB  - PURPOSE: At our institution, the availability of a shielded procedure room with
      in-room CT-on-rails imaging allows for the exploration of a high-dose-rate (HDR)
      brachytherapy approach for breast intraoperative radiation therapy (IORT). We
      hypothesize that HDR brachytherapy will permit a higher prescription dose without
      increasing toxicity. In this study, we compare the dosimetry of intraoperative
      HDR brachytherapy, using multilumen balloon applicator, to IORT with a 50 kV
      source and then select a prescription dose for a subsequent clinical trial.
      METHODS AND MATERIALS: The CT scans of 14 patients who had previously received
      multilumen balloon-based breast brachytherapy were replanned to a standard
      prescription to the target volume. The same 14 cases were planned to the
      specifications of a 50 kV x-ray system. Uniform volume optimization and
      prescription doses were used to permit direct comparisons. All plans were
      evaluated for the dose homogeneity index, tumor coverage, and dose to normal
      tissues, including skin, ribs, and heart (for left breast plans). RESULTS: The
      HDR brachytherapy plans were superior to 50 kV superficial photon plans for IORT
      in all dosimetric parameters except for the heart and rib dosimetric parameters.
      Prescription dose of 12.5 Gy to the planning target volume for evaluation yielded
      a dose to 95 percent of the balloon surface of 19.7 Gy. CONCLUSIONS: Image-guided
      HDR intraoperative brachytherapy with a multilumen balloon applicator provides
      superior target volume coverage compared with 50 kV photons, while maintaining
      doses within tolerance limits for normal tissues. An ongoing prospective clinical
      trial will evaluate the safety and feasibility of this technique.

PMID- 24933341
TI  - Prenatal diagnosis of 5p deletion syndrome in a female fetus leading to
      identification of the same diagnosis in her mother.

PMID- 24933340
TI  - Diabetes care and complications in primary care in the Tshwane district of South
      Africa.
AB  - AIMS: To describe the diabetic population receiving primary care from the Tshwane
      district public health services and to assess the quality of care of members of
      this population, their level of disease control and the extent of their
      complications. METHODS: A cluster-randomised trial was conducted in 12 primary
      care clinics in Tshwane district. A total of 599 diabetic patients attending
      these clinics for review were consecutively interviewed and clinically examined.
      Data on the care received was also obtained from their clinical records for the
      previous 12 months. Patients randomised to the active arm of the study were
      screened for complications. RESULTS: The mean age was 58 years and 80.5% had a
      body mass index (BMI) >=25 kg/m(2). Sixty-eight percent of patients were female.
      Acceptable glycaemic control and LDL-cholesterol were found for only 27% and 33%
      of patients, respectively (HbA1c<7%; LDL<2.5 mmol/l). Despite more than 79% of
      patients reporting to be hypertensive, 68% of patients had a systolic blood
      pressure above 130 mmHg and 64% had a diastolic blood pressure above 80 mmHg.
      Evaluating patient records of the preceding year, screening for eye complications
      was only reported in 8.2%, feet complications in 6.5%, kidney complications in
      21.4% and cardiovascular complications in 7.8%. The screening prevalences found
      were 29% for retinopathy, 22% for maculopathy, 5% for neuropathy
      (neurothesiometer), 7% for nephropathy (eGFR stages 3-5), 17% for possible
      infarction (Rose questionnaire) and 36% for severe erectile dysfunction (SHIM
      questionnaire). CONCLUSION: Diabetes care and screening for complications at
      primary care level in the Tshwane district were found to be sub-optimal. Measures
      should be taken to address this.

PMID- 24933343
TI  - Inhibited osteoclastic bone resorption through alendronate treatment in rats
      reduces severe osteoarthritis progression.
AB  - Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by
      progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced
      subchondral bone remodeling, osteophyte formation and synovial thickening.
      Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and
      results in reduced bone remodeling. This study investigated the effects of pre
      emptive use of ALN on OA related osteoclastic subchondral bone resorption in an
      in vivo rat model for severe OA. Using multi-modality imaging we measured effects
      of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced
      in left rat knees using papain injections in combination with a moderate running
      protocol. Twenty rats were treated with subcutaneous ALN injections and compared
      to twenty untreated controls. Animals were longitudinally monitored for 12weeks
      with in vivo MUCT to measure subchondral bone changes and SPECT/CT to determine
      synovial macrophage activation using a folate-based radiotracer. Articular
      cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced MUCT and
      histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage
      thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a
      result we found less subchondral plate porosity and reduced osteophytosis. ALN
      treatment did not reduce subchondral sclerosis. However, after the OA induction
      phase, ALN treatment protected cartilage ECM from degradation and reduced
      synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG
      content of tibia cartilage in healthy joints. Our data was consistent with the
      hypothesis that osteoclastic bone resorption might play an important role in OA
      and may be a driving force for progression of the disease. However, our study
      suggest that this effect might not solely be effects on osteoclastic activity,
      since ALN treatment also influenced macrophage functioning. Additionally, ALN
      treatment and physical activity exercised a positive effect in healthy control
      joints, which increased cartilage sGAG content. More research on this topic might
      lead to novel insights as to improve cartilage quality. 

PMID- 24933342
TI  - Osteocyte-derived RANKL is a critical mediator of the increased bone resorption
      caused by dietary calcium deficiency.
AB  - Parathyroid hormone (PTH) excess stimulates bone resorption. This effect is
      associated with increased expression of the osteoclastogenic cytokine receptor
      activator of nuclear factor kappaB ligand (RANKL) in bone. However, several
      different cell types, including bone marrow stromal cells, osteocytes, and T
      lymphocytes, express both RANKL and the PTH receptor and it is unclear whether
      RANKL expression by any of these cell types is required for PTH-induced bone
      loss. Here we have used mice lacking the RANKL gene in osteocytes to determine
      whether RANKL produced by this cell type is required for the bone loss caused by
      secondary hyperparathyroidism induced by dietary calcium deficiency in adult
      mice. Thirty days of dietary calcium deficiency caused bone loss in control mice,
      but this effect was blunted in mice lacking RANKL in osteocytes. The increase in
      RANKL expression in bone and the increase in osteoclast number caused by dietary
      calcium deficiency were also blunted in mice lacking RANKL in osteocytes. These
      results demonstrate that RANKL produced by osteocytes contributes to the
      increased bone resorption and the bone loss caused by secondary
      hyperparathyroidism, strengthening the evidence that osteocytes are an important
      target cell for hormonal control of bone remodeling. 

PMID- 24933345
TI  - Mortality in British hip fracture patients, 2000-2010: a population-based
      retrospective cohort study.
AB  - BACKGROUND: Data on recent trends in mortality after hip fracture are scarce.
      Aims were therefore to examine secular trends in all-cause and cause-specific
      mortality post hip fracture and to compare this to the general population from
      2000 to 2010. METHODS: Population-based cohort study within the United Kingdom
      Clinical Practice Research Datalink and linked to cause of death data for 57.7%
      of patients. Patients with a first hip fracture (n=31,495) were matched to up to
      four controls by age, sex, index date, and practice. All subjects were followed
      for death, and lifestyle, disease and medication history adjusted hazard ratios
      (HRs) were calculated. RESULTS: One-year all-cause mortality after hip fracture
      declined from 2009 and was 14% lower after, compared with before 2009 (22.3% to
      20.5%, adj. HR 0.86, 95% CI: 0.81-0.92). The decline was observed for males
      (>=75years) and females (>=85years). Significant contributors to the decline in
      mortality post hip fracture were respiratory infections in females as were
      malignant diseases in males. However, one-year all-cause mortality remained
      unaltered over the decade when compared to controls with a 3.5-fold and 2.4-fold
      increased risk in males and females respectively. No significant changes were
      observed in the relative risks for one-year cause-specific mortality for both
      genders. CONCLUSIONS: One-year mortality after hip fracture has declined over the
      last decade in the UK. However, the difference in one-year mortality between hip
      fracture patients and the general population remained unaltered. These
      observations highlight the need for the continued implementation of evidence
      based standards for good hip fracture care.

PMID- 24933344
TI  - Ginsenoside-Rb2 displays anti-osteoporosis effects through reducing oxidative
      damage and bone-resorbing cytokines during osteogenesis.
AB  - Reactive oxygen species (ROS) are a significant pathogenic factor of
      osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted
      from ginseng, is a potent antioxidant that generates interest regarding the bone
      metabolism area. We tested the potential anti-osteoporosis effects of Rb2 and its
      underlying mechanism in this study. We produced an oxidative damage model induced
      by hydrogen peroxide (H2O2) in osteoblastic MC3T3-E1 cells to test the essential
      anti-osteoporosis effects of Rb2in vitro. The results indicated that treatment of
      0.1 to 10MUM Rb2 promoted the proliferation of MC3T3-E1 cells, improved alkaline
      phosphatase (ALP) expression, elevated calcium mineralization and mRNA
      expressions of Alp, Col1a1, osteocalcin (Ocn) and osteopontin (Opn) against
      oxidative damage induced by H2O2. Importantly, Rb2 reduced the expression levels
      of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and
      inhibited the H2O2-induced production of ROS. The in vivo study indicated that
      the Rb2 administered for 12weeks partially decreased blood malondialdehyde (MDA)
      activity and elevated the activity of reduced glutathione (GSH) in ovariectomized
      (OVX) mice. Moreover, Rb2 improved the micro-architecture of trabecular bones and
      increased bone mineral density (BMD) of the 4th lumbar vertebrae (L4) and the
      distal femur. Altogether, these results demonstrated that the potential anti
      osteoporosis effects of Rb2 were linked to a reduction of oxidative damage and
      bone-resorbing cytokines, which suggests that Rb2 might be effective in
      preventing and alleviating osteoporosis. 

PMID- 24933346
TI  - Molecular mechanisms underlying skeletal growth arrest by cutaneous scarring.
AB  - In pediatric surgeries, cutaneous scarring is frequently accompanied by an arrest
      in skeletal growth. The molecular mechanisms responsible for this effect are not
      understood. Here, we investigated the relationship between scar contracture and
      osteogenesis. An excisional cutaneous wound was made on the tail of neonatal
      mice. Finite element (FE) modeling of the wound site was used to predict the
      distribution and magnitude of contractile forces within soft and hard tissues.
      Morphogenesis of the bony vertebrae was monitored by micro-CT analyses, and
      vertebral growth plates were interrogated throughout the healing period using
      assays for cell proliferation, death, differentiation, as well as matrix
      deposition and remodeling. Wound contracture was grossly evident on post-injury
      day 7 and accompanying it was a significant shortening in the tail. FE modeling
      indicated high compressive strains localized to the dorsal portions of the
      vertebral growth plates and intervertebral disks. These predicted strain
      distributions corresponded to sites of increased cell death, a cessation in cell
      proliferation, and a loss in mineralization within the growth plates and IVD.
      Although cutaneous contracture resolved and skeletal growth rates returned to
      normal, vertebrae under the cutaneous wound remained significantly shorter than
      controls. Thus, localized contractile forces generated by scarring led to spatial
      alterations in cell proliferation, death, and differentiation that inhibited bone
      growth in a location-dependent manner. Resolution of cutaneous scarring was not
      accompanied by compensatory bone growth, which left the bony elements permanently
      truncated. Therefore, targeting early scar reduction is critical to preserving
      pediatric bone growth after surgery. 

PMID- 24933347
TI  - The fracture sites of atypical femoral fractures are associated with the weight
      bearing lower limb alignment.
AB  - PURPOSE: Atypical femoral fractures (AFFs) are stress-related fractures that are
      speculated to associate with long-term treatment with bisphosphonates for
      osteoporosis. A history of AFF is a high risk factor for the development of a
      subsequent AFF in the same location of the contralateral femur, suggesting that a
      patient's individual anatomical factor(s) are related to the fracture site of
      AFFs. In this study, we investigated the radiographs of fourteen AFFs (four
      bilateral fractures among ten patients) treated at six hospitals associated with
      our university between 2005 and 2010. The fracture site and standing femorotibial
      angle (FTA), which reflects the mechanical axis of the lower limb, were measured
      on weight-bearing lower limb radiographs. The fracture site and FTA of patients
      with typical femoral fractures (TFF) were compared to those of patients with
      AFFs. The correlations were examined using Spearman's rank correlation
      coefficients. The fracture locations in the femora were almost the same in the
      patients with bilateral AFFs. There was a positive correlation between the
      fracture site and the standing FTA in the patients with AFFs (r=0.82, 95%
      confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA
      (varus alignment), the more distal the site of the fracture in the femur. The FTA
      of the patients with atypical diaphyseal femoral fracture were significantly
      larger compared to that of those with not only atypical subtrochanteric fractures
      but also TFFs. In conclusion, the fracture sites of AFFs are associated with the
      standing lower limb alignment, while those of TFFs are not.

PMID- 24933348
TI  - Anna-Monika Award Lecture, DGPPN Kongress, 2013: the role of the hypothalamic
      pituitary-adrenal (HPA) axis in the pathogenesis of psychotic major depression.
AB  - OBJECTIVES: This Anna Monika Award Lecture updates the role of the hypothalamic
      pituitary-adrenal (HPA) axis in the pathogenesis and treatment of psychotic major
      depression (PMD). METHODS: Published reports from our group and others on the
      clinical phenomenology (including cognition), HPA axis activity, and genetics of
      PMD are reviewed as are published trials of the GR antagonist, mifepristone.
      RESULTS: Current prevalence of PMD is 0.4%. PMD patients demonstrate significant
      elevations in HPA activity (e.g., particularly high rates of dexamethasone non
      suppression, high post-dexamethasone cortisol, etc.) as well as significant
      impairment in cognition (attention, executive function/response inhibition and
      verbal and visual memory). High cortisol levels correlate with a number of
      cognitive deficits (e.g., verbal memory). Allelic variants of the glucocorticoid
      receptor (GR) gene contribute significantly to both cortisol levels and to
      measures of psychosis; corticotropin-releasing hormone receptor 1 variants
      contribute to measures of depression and psychosis. GR antagonists have produced
      rapid improvement in psychotic symptoms, although failed trials indicate a
      therapeutic blood level that may require a dose of 1,200 mg/day that is much
      higher than the commonly tested 600 mg/day. CONCLUSIONS: HPA axis over-activity
      appears to play a major role in the pathogenesis of PMD and is a target of drug
      development.

PMID- 24933349
TI  - Cutaneous microbiome studies in the times of affordable sequencing.
AB  - BACKGROUND: Skin is our first line of defense against pathogenic microorganisms
      and the intimate contact between the epidermis and microbes has been well known.
      PURPOSES: Microbes that cause infection are associated with inflammatory
      dermatoses and exacerbate wound healing. It is therefore of vital importance to
      understand the intricacies of skin-microbiota interactions. However, until
      recently our knowledge and understanding was limited by being unable to deal with
      uncultivatable microorganisms, which constitute a large majority. BASIC
      PROCEDURES: Recent advances in DNA sequencing methodologies, analysis tools and
      affordability led to major breakthroughs in defining the cutaneous microbiome.
      MAIN FINDINGS: We now know that four phyla, Actinobacteria, Firmicytes,
      Proteobacteria and Bacteroidetes, constitute preponderance of skin bacteria,
      while Malassezia dominates the fungal microbiome. We know that there are some 300
      different bacteria inhabiting our skin. We also know that there is remarkable
      interpersonal variation, that the microbiota change over time, that different
      body sites harbor specific microbial arrays and that microbiota
      characteristically change in skin diseases. PRINCIPAL CONCLUSIONS: The recent
      advances led to appreciation that microbes are, for the most part, our allies,
      useful and protective, and that with increased understanding we will be able to
      harness our cutaneous friends to maintain and promote our health.

PMID- 24933351
TI  - Spontaneous intracranial hypotension in a case of systemic lupus erythematosus.

PMID- 24933350
TI  - Engineered platform for bioethylene production by a cyanobacterium expressing a
      chimeric complex of plant enzymes.
AB  - Ethylene is an industrially important compound, but more sustainable production
      methods are desirable. Since cellulosomes increase the ability of cellulolytic
      enzymes by physically linking the relevant enzymes via dockerin-cohesin
      interactions, in this study, we genetically engineered a chimeric cellulosome
      like complex of two ethylene-generating enzymes from tomato using cohesin
      dockerins from the bacteria Clostridium thermocellum and Acetivibrio
      cellulolyticus. This complex was transformed into Escherichia coli to analyze
      kinetic parameters and enzyme complex formation and into the cyanobacterium
      Synechococcus elongatus PCC 7942, which was then grown with and without 0.1 mM
      isopropyl beta-D-1-thiogalactopyranoside (IPTG) induction. Only at minimal
      protein expression levels (without IPTG), the chimeric complex produced 3.7 times
      more ethylene in vivo than did uncomplexed enzymes. Thus, cyanobacteria can be
      used to sustainably generate ethylene, and the synthetic enzyme complex greatly
      enhanced production efficiency. Artificial synthetic enzyme complexes hold great
      promise for improving the production efficiency of other industrial compounds.

PMID- 24933352
TI  - Platelet-rich plasma therapy is effective for the treatment of refractory skin
      ulcers in patients with systemic sclerosis.

PMID- 24933353
TI  - Robust stochastic stability of discrete-time fuzzy Markovian jump neural
      networks.
AB  - This paper focuses the issue of robust stochastic stability for a class of
      uncertain fuzzy Markovian jumping discrete-time neural networks (FMJDNNs) with
      various activation functions and mixed time delay. By employing the Lyapunov
      technique and linear matrix inequality (LMI) approach, a new set of delay
      dependent sufficient conditions are established for the robust stochastic
      stability of uncertain FMJDNNs. More precisely, the parameter uncertainties are
      assumed to be time varying, unknown and norm bounded. The obtained stability
      conditions are established in terms of LMIs, which can be easily checked by using
      the efficient MATLAB-LMI toolbox. Finally, numerical examples with simulation
      result are provided to illustrate the effectiveness and less conservativeness of
      the obtained results. 

PMID- 24933354
TI  - Improved delay-dependent stability analysis for neural networks with time-varying
      delays.
AB  - In this paper, the problem of delay-dependent asymptotic stability analysis for
      neural networks with time-varying delays is considered. A new class of Lyapunov
      functional is proposed by considering the information of neuron activation
      functions adequately. By using the delay-partitioning method and the reciprocally
      convex technique, some less conservative stability criteria are obtained in terms
      of linear matrix inequalities (LMIs). Finally, two numerical examples are given
      to illustrate the effectiveness of the derived method. 

PMID- 24933355
TI  - Fractional-order system identification and proportional-derivative control of a
      solid-core magnetic bearing.
AB  - This paper presents the application of fractional-order system identification
      (FOSI) and proportional-derivative (PD(u)) control to a solid-core magnetic
      bearing (MB). A practical strategy for closed-loop incommensurate FOSI along with
      a modified error criterion is utilized to model the MB system and a
      corresponding, verification experiment is carried out. Based on the identified
      model, integer-order (IO) PD and fractional-order (FO) PD(u) controllers are
      designed and compared with the same specifications. Besides, the relation between
      the two categories of controllers is discussed by their feasible control zones.
      Final simulation and experimental results show that the FO PD(u) controller can
      significantly improve the transient and steady-state performance of the MB system
      comparing with the IO PD controller. 

PMID- 24933357
TI  - Synthesis of POSS-based ionic conductors with low glass transition temperatures
      for efficient solid-state dye-sensitized solar cells.
AB  - Replacing liquid-state electrolytes with solid-state electrolytes has been proven
      to be an effective way to improve the durability of dye-sensitized solar cells
      (DSSCs). We report herein the synthesis of amorphous ionic conductors based on
      polyhedral oligomeric silsesquioxane (POSS) with low glass transition
      temperatures for solid-state DSSCs. As the ionic conductor is amorphous and in
      the elastomeric state at the operating temperature of DSSCs, good pore filling in
      the TiO2 film and good interfacial contact between the solid-state electrolyte
      and the TiO2 film can be guaranteed. When the POSS-based ionic conductor
      containing an allyl group is doped with only iodine as the solid-state
      electrolyte without any other additives, power conversion efficiency of 6.29% has
      been achieved with good long-term stability under one-sun soaking for 1000 h. 

PMID- 24933356
TI  - Conformational switch of insulin-binding aptamer into G-quadruplex induced by K+
      and Na+: an experimental and theoretical approach.
AB  - Guanine-rich sequences can form the G-quadruplex structure in the presence of
      specific metal ions. Here, circular dichroism, UV-vis absorption, fluorescence,
      and molecular dynamics simulation studies revealed that insulin-binding aptamer
      (IBA) could form an intramolecular G-quadruplex structure after binding K(+).
      Circular dichroism (CD) spectra demonstrated that IBA could fold into a parallel
      G-quadruplex with a strong positive peak at 263 nm. Analysis of equilibrium
      titration data revealed that cation binding was cooperative with the Hill
      coefficient of 2.01 in K(+) and 1.90 in Na(+). Thermal denaturation assays
      indicated that K(+)-induced G-quadruplex is more stable than Na(+)-induced
      structure. Folding of IBA into G-quadruplex leading to the contact quenching
      occurs as a result of the formation of a nonfluorescent complex between donor and
      acceptor. Based on fluorescence quenching of IBA folding, a potassium-sensing
      aptasensor in the range of 0-1.4 mM was proposed. Since the quenching process was
      predominantly static, the binding constant and the number of binding sites were
      determined. In this research, based on the experimental data, the initial model
      of IBA G-quadruplex was constructed by molecular modeling method. The modeling
      structure of IBA is an intramolecular parallel-strand quadruplex conformation
      with two guanine tetrads. The extended molecular dynamics simulation for the
      model indicated that the G-quadruplex maintains its structure very well in
      aqueous solution in presence of K(+) in the central cavity. In contrast, it was
      demonstrated that the G-quadruplex structure of model in the water collapses in
      absence of this cation.

PMID- 24933358
TI  - Otologic complications of Stevens-Johnson Syndrome and Toxic Epidermal
      Necrolysis.
AB  - This case report demonstrates the otologic complications of Stevens-Johnson
      Syndrome and Toxic Epidermal Necrolysis (SJS/TEN). A five year-old male was
      admitted to the burn unit with the diagnosis of SJS/TEN believed secondary to
      acetaminophen use. After resolution of the acute phase, the patient was left with
      a severe auricular deformity with scarring and complete occlusion of the right
      external auditory canal (EAC). The patient underwent meatoplasty, canaloplasty,
      and tympanoplasty with subsequent placement of a molded stent in order to
      maintain patency of his EAC. Four years later, the patient has a patent right EAC
      with adequate hearing. 

PMID- 24933359
TI  - A novel splice site mutation in DFNA5 causes late-onset progressive non-syndromic
      hearing loss in a Chinese family.
AB  - OBJECTIVES: Mutations in DFNA5 may lead to autosomal dominant non-syndromic
      sensorineural hearing loss (NSHL). To date, only four DFNA5 mutations have been
      reported, all resulting in skipping of exon 8 at the mRNA level. In this study,
      we aim to characterize the clinical features and the genetic cause of a Chinese
      DFNA5 family. METHODS: Targeted next-generation sequencing of 79 known deafness
      genes was performed in the proband. Co-segregation between the disease phenotype
      and the potentially pathogenic variant was confirmed in all family members by
      Sanger sequencing. RESULTS: A novel heterozygous c.991-2A>G mutation in DFNA5 was
      identified in this family segregating with the autosomal dominant, late-onset
      NSHL. This mutation was located in the conventional splice site in intron 7 and
      was likely to result in skipping of exon 8. The severity of hearing impairment
      varied intrafamilially. CONCLUSION: We identified a novel c.991-2A>G mutation in
      DFNA5 which again may lead to exon 8 skipping at the mRNA level. Our findings
      supported that the DFNA5-associated NSHL results from a specific gain-of-function
      mechanism.

PMID- 24933360
TI  - Visual and neurologic deterioration in otogenic lateral sinus thrombosis: 15 year
      experience.
AB  - OBJECTIVES: Otogenic lateral sinus thrombosis is a rare complication of acute
      otitis media whose clinical presentation has changed with the early use of
      antibiotics. The aim of this study was to analyze the changing clinical signs,
      vaccination status, therapeutic management and outcome of these patients.
      METHODS: Retrospective chart review of 10 children treated with otogenic lateral
      sinus thrombosis in a tertiary level teaching hospital in Budapest, Hungary, from
      January 1998 till August 2013. RESULTS: Patients were divided into Early and Late
      presenting groups. In the Early presenting group, sepsis developed within one
      week after the onset of acute otitis media. At admission otological symptoms were
      predominant. The Late presenting group experienced acute otitis media several
      weeks prior to presentation and in this group neurologic symptoms dominated the
      clinical picture at admission. All patients received antibiotics. Eight of them
      were also treated with low molecular weight heparin. All children underwent
      cortical mastoidectomy. After surgery, the clinical signs of elevated
      intracranial pressure transiently worsened. This manifested as progression of
      papilledema in seven children, causing severe visual disturbance in two cases.
      After medical treatment and serial lumbar punctures all patients except one
      recovered. This child has permanent visual acuity failure of 0.5D unilaterally.
      At one year follow up complete and partial recanalization were noted in five and
      two patients, respectively. CONCLUSIONS: After mastoidectomy the signs of
      elevated intracranial pressure can transiently worsen, papilledema can progress.
      Daily bedside monitoring of visual acuity and regular ophthalmoscopy with
      neurologic examination is recommended during hospitalization. Close follow up is
      advised up to one year. When the dominant sinus is occluded, the clinical
      scenario is more protracted and severe.

PMID- 24933361
TI  - Employment status of people with mental illness: national survey data from 2009
      and 2010.
AB  - OBJECTIVE: The aim of this study was to describe employment according to mental
      illness severity in the United States during 2009 and 2010. METHODS: The sample
      included all working-age participants (ages 18-64) from the 2009 and 2010
      National Survey on Drug Use and Health (N=77,326). Two well-established scales of
      mental health distinguished participants with none, mild, moderate, and serious
      mental illness. Analyses compared employment rate and income by mental illness
      severity. Employment status was estimated with logistic regression models that
      controlled for demographic characteristics and substance use disorders. In
      secondary analyses the relationship between mental illness and employment was
      assessed for variation by age and education status. RESULTS: Employment rates
      decreased with increasing mental illness severity (no mental illness, 75.9%
      employment; mild, 68.8%; moderate, 62.7%; and serious, 54.5%, p<.001). Over a
      third of people with serious mental illness, 38.5%, had incomes <$10,000
      (compared with 23.1% of people with no mental illness, p<.001). The gap in
      adjusted employment rates comparing persons with serious versus no mental illness
      was 1% among people 18-25 years old versus 21% among people 50-64 (p<.001).
      CONCLUSIONS: More severe mental illness was associated with lower employment
      rates in 2009 and 2010. People with serious mental illness are less likely than
      people with no, mild, or moderate mental illness to be employed after age 49.

PMID- 24933362
TI  - FGFR3 expression in primary invasive bladder cancers and matched lymph node
      metastases.
AB  - PURPOSE: FGFR3 is considered a good therapeutic target for bladder cancer.
      However, to our knowledge it is unknown whether the FGFR3 status of primary
      tumors is a surrogate for related metastases, which must be targeted by FGFR
      targeted systemic therapies. We assessed FGFR3 protein expression in primary
      bladder tumors and matched nodal metastases. MATERIALS AND METHODS: We examined
      matched primary tumor and nodal metastases from 150 patients with bladder cancer
      clinically staged as N0M0. Four samples per patient were incorporated into a
      tissue microarray and FGFR3 expression was assessed by immunohistochemistry.
      FGFR3 expression was tested for an association with categorical clinical data
      using the Fisher exact test, and with overall and recurrence-free survival by
      Kaplan-Meier analysis. RESULTS: Duplicate spots from primary tumors and lymph
      node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p
      <0.001). Overall FGFR protein expression levels did not differ between primary
      and metastatic lesions (p = 0.78). Up-regulated expression was recorded in 53 of
      106 evaluable primary tumor spots and 56 matched metastases. Concordance of FGFR3
      expression levels in 79 matched primary tumor and metastasis specimens was high
      (OR 8.45, p <0.001). In 15 and 12 patients expression was up-regulated in only
      metastasis and in only the primary tumor, respectively. Overall and recurrence
      free survival was not related to FGFR3 expression. CONCLUSIONS: FGFR3 expression
      in matched primary and metastasized bladder cancer specimens showed good but not
      absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide
      the selection of FGFR targeted therapy.

PMID- 24933363
TI  - Anterior vaginal wall suspension procedure for moderate bladder and uterine
      prolapse as a method of uterine preservation.
AB  - PURPOSE: We report our experience with anterior vaginal wall suspension for
      moderate anterior vaginal compartment prolapse and uterine descent less than
      stage 2. MATERIALS AND METHODS: Data on patients who underwent anterior vaginal
      wall suspension with uterine preservation by hysteropexy and had a 1-year minimum
      followup were extracted from a long-term, prospective, institutional review board
      approved, surgical prolapse database. The indication for uterine preservation was
      uterine descent not beyond the distal third of the vagina with traction with the
      patient under anesthesia, and negative Pap smear and pelvic ultrasound
      preoperatively. The upper suture of the anterior vaginal wall suspension secures
      the cardinal ligament complex, allowing for uterine suspension once the suture is
      transferred suprapubically. Failure was defined as prolapse recurrence greater
      than stage 2 on physical examination or the need for reoperation for uterine
      descent. Outcome measures at serial intervals included validated questionnaires,
      physical examination, standing voiding cystourethrogram at 6 months
      postoperatively and complications. RESULTS: From May 1996 to March 2012, 52 of
      739 patients met inclusion criteria. Mean followup was 55 months (range 12 to
      175, median 44). Mean patient age was 62 years (range 38 to 81), mean body mass
      index was 26.7 kg/m(2) (range 18.3 to 49.4) and mean parity was 2.7. There were
      no transfusions or intraoperative complications. Overall 7 (13%) patients
      underwent subsequent hysterectomy for uterine prolapse recurrence at 7 months to
      6 years postoperatively. CONCLUSIONS: The anterior vaginal wall suspension
      procedure offers a simple, mesh-free surgical alternative with acceptable long
      term followup in patients with moderate uterine prolapse who wish for uterine
      preservation. However, patients should be appropriately counseled about the low
      risk of subsequent hysterectomy.

PMID- 24933364
TI  - First measurements of a carbon dioxide plume from an industrial source using a
      ground based mobile differential absorption lidar.
AB  - The emission of carbon dioxide (CO2) from industrial sources is one of the main
      anthropogenic contributors to the greenhouse effect. Direct remote sensing of CO2
      emissions using optical methods offers the potential for the identification and
      quantification of CO2 emissions. We report the development and demonstration of a
      ground based mobile differential absorption lidar (DIAL) able to measure the mass
      emission rate of CO2 in the plume from a power station. To our knowledge DIAL has
      not previously been successfully applied to the measurement of emission plumes of
      CO2 from industrial sources. A significant challenge in observing industrial CO2
      emission plumes is the ability to discriminate and observe localised
      concentrations of CO2 above the locally observed background level. The objectives
      of the study were to modify our existing mobile infrared DIAL system to enable
      CO2 measurements and to demonstrate the system at a power plant to assess the
      feasibility of the technique for the identification and quantification of CO2
      emissions. The results of this preliminary study showed very good agreement with
      the expected emissions calculated by the site. The detection limit obtained from
      the measurements, however, requires further improvement to provide quantification
      of smaller emitters of CO2, for example for the detection of fugitive emissions.
      This study has shown that in principle, remote optical sensing technology will
      have the potential to provide useful direct data on CO2 mass emission rates. 

PMID- 24933369
TI  - A Shining Light in Canada's Health Information System.

PMID- 24933366
TI  - Quantitative proteomic analysis identifies targets and pathways of a 2
      aminobenzamide HDAC inhibitor in Friedreich's ataxia patient iPSC-derived neural
      stem cells.
AB  - Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors
      show promise as therapeutics for the neurodegenerative diseases Friedreich's
      ataxia (FRDA) and Huntington's disease (HD). While it is clear that HDAC3 is one
      of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of
      other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial
      effects of these compounds in FRDA and HD, and other HDAC interacting proteins
      may be impacted by the compound. To this end, we synthesized activity-based
      profiling probe (ABPP) versions of one of our HDAC inhibitors (compound 106), and
      in the present study we used a quantitative proteomic method coupled with
      multidimensional protein identification technology (MudPIT) to identify the
      proteins captured by the ABPP 106 probe. Nuclear proteins were extracted from
      FRDA patient iPSC-derived neural stem cells, and then were reacted with control
      and ABPP 106 probe. After reaction, the bound proteins were digested on the
      beads, and the peptides were modified using stable isotope-labeled formaldehyde
      to form dimethyl amine. The selectively bound proteins determined by mass
      spectrometry were subjected to functional and pathway analysis. Our findings
      suggest that the targets of compound 106 are involved not only in transcriptional
      regulation but also in posttranscriptional processing of mRNA. 

PMID- 24933368
TI  - Dynamical phenotyping: using temporal analysis of clinically collected
      physiologic data to stratify populations.
AB  - Using glucose time series data from a well measured population drawn from an
      electronic health record (EHR) repository, the variation in predictability of
      glucose values quantified by the time-delayed mutual information (TDMI) was
      explained using a mechanistic endocrine model and manual and automated review of
      written patient records. The results suggest that predictability of glucose
      varies with health state where the relationship (e.g., linear or inverse) depends
      on the source of the acuity. It was found that on a fine scale in parameter
      variation, the less insulin required to process glucose, a condition that
      correlates with good health, the more predictable glucose values were.
      Nevertheless, the most powerful effect on predictability in the EHR subpopulation
      was the presence or absence of variation in health state, specifically, in- and
      out-of-control glucose versus in-control glucose. Both of these results are
      clinically and scientifically relevant because the magnitude of glucose is the
      most commonly used indicator of health as opposed to glucose dynamics, thus
      providing for a connection between a mechanistic endocrine model and direct
      insight to human health via clinically collected data. 

PMID- 24933370
TI  - Administrative data and the manitoba centre for health policy: some reflections.
AB  - The authors review their 30 years' experience in determining the best research
      applications for routinely collected data from ministries of health, education
      and social services. They describe the rich research opportunities afforded by 40
      years of data on health - i.e., every patient contact with hospitals, physicians,
      drugs and more - from the problems encountered in convincing an academic journal
      that meaningful findings could be culled from information collected on paying
      bills and tracking patients, through studies on education (enrolment, grades,
      standardized tests for grades 1 to 12), family characteristics (residential
      moves, marital formation and breakdown, number and timing of births) and social
      services (welfare recipients, children taken into care, protection services
      offered children in the family). They also detail how and why the Manitoba Centre
      for Health Policy was founded, and how it has continued through multiple
      ministerial, deputy and government changes. 

PMID- 24933371
TI  - The manitoba centre for health policy: a case study.
AB  - CONTEXT: The Manitoba Centre for Health Policy (MCHP) is a university research
      centre with a long-standing contractual arrangement with government. OBJECTIVE:
      The purpose of this project was to examine the facilitators and challenges in the
      development, establishment and continuation of MCHP. METHODS: In-depth, semi
      structured interviews with 28 participants selected purposefully and a document
      review were conducted and analyzed using qualitative methods. RESULTS: Although a
      unique confluence of factors facilitated MCHP's establishment, participants
      viewed safeguards to credibility (arm's-length from government; guaranteed
      academic freedom) along with powerful advocates as key to longevity. Other
      factors that participants discussed as important to sustainability included
      excellence in scholarship; thorough protection of privacy; stable funding;
      incremental growth; teamwork; leadership; nurturing of relationships; and
      authentic partnerships. CONCLUSIONS: MCHP has demonstrated that using local
      administrative data to address policy-related research questions is of enduring
      value to local and provincial communities, and also has national and
      international relevance.

PMID- 24933372
TI  - Straw into Gold: Lessons Learned (and Still Being Learned) at the Manitoba Centre
      for Health Policy.
AB  - What lessons have we learned at the Manitoba Centre for Health Policy (MCHP)
      about knowledge translation (KT) over the past 20 years, and what is our vision
      for the future? How does that KT interrelate with our other activities - research
      and the Population Health Data Repository? Who first noticed that "there's gold
      in them thar hills," and what did they do about it? How did we weave
      administrative database "straw" into gold, how have we panned for gold and how do
      we look for the pot of gold in the future? This paper describes how MCHP began
      with an integrated KT research relationship with government, and through The Need
      to Know Team, extended KT to regional health authority planners. It describes the
      various push-pull KT mechanisms that MCHP has used, including dissemination of
      research to planners through interactive workshops, and to other researchers
      through Web-based resources. 

PMID- 24933373
TI  - The role of administrative record linkage in creating trajectories of early human
      development.
AB  - Early childhood development (ECD) is a significant social determinant of health.
      Monitoring ECD to reveal trends and patterns of development requires high-quality
      information on a population from infancy through adulthood. This study linked
      data from the Early Development Instrument (EDI), administered in senior
      kindergarten, with data from the Foundation Skills Assessment (FSA), graduation
      status and SES to show that Vancouver schools with poor FSA results also had high
      proportions of children with low EDI and SES scores. Linking EDI data to data on
      pregnancy, birth, medical history, hospital care and success in school would
      enable the creation of normative EDC trajectories for all children. A person
      specific, anonymized, population-based record linkage system is an indispensable
      prerequisite for creating and monitoring developmental trajectories. 

PMID- 24933374
TI  - Can joined-up data lead to joined-up thinking? The Western Australian
      developmental pathways project.
AB  - Modern societies are challenged by "wicked problems" - by definition, those that
      are difficult to define, multi-causal and hard to treat. Problems such as low
      birth weight, obesity, mental ill health, teenage pregnancy, educational
      difficulties and juvenile crime fit this category. Given the complex nature of
      these problems, they require the best data in order to measure them, guide policy
      frameworks and evaluate whether the steps taken to address them are actually
      making a difference. What such problems really require are joined-up approaches
      to enable effective solutions. In this paper, we describe a unique initiative to
      encourage a more preventive, whole-of-government approach to these problems - the
      Developmental Pathways Project, which has enabled the linkage of a large number
      of de-identified administrative databases in order to explore the pathways into
      and out of the negative outcomes affecting our children and youth. This project
      has not only enabled the linkage of agency data, but also of agency personnel, in
      order to improve and promote cross-agency research, policy and preventive
      solutions. Through the use of these linkages we are attempting to shift the
      paradigm to encourage agencies to appreciate that these "wicked problems" demand
      a preventive approach, as well as the provision of effective services for those
      already affected. 

PMID- 24933375
TI  - How has health services research made a difference?
AB  - Health services research (HSR) is commonly conceived as an applied discipline
      whose success is defined by its tangible impact on policy, practice or both. In
      Canada there has been a concerted effort to engage decision-makers in informing
      the research agenda. While it is admirable to aspire to practical utility, the
      HSR community has no control over the ultimate disposition of its work.
      Furthermore, the conditions for change must be present if the pathway from
      relevant, high-quality research to application is to be relatively smooth and
      immediate. In such cases, the changes may have occurred regardless of whether the
      research to support them took place. An examination of some widely renowned HSR
      reveals that timely and significant impact is relatively rare. Moreover, research
      that fundamentally changes how we view the world plays out over decades; it would
      be impossible to act on it in the short term, and in some cases it is not clear
      what ought to be done. The implications are that the first duty of HSR is to seek
      truth, and that funding and decision-making communities should define "useful"
      broadly, from a longer-term perspective. Taking the wide and the long view will
      in the end generate a greater return on investment in HSR than focusing too
      narrowly on contemporary preoccupations. 

PMID- 24933376
TI  - Panning for Population Gold: 20 Years of Research at MCHP.

PMID- 24933377
TI  - The Whole Is Greater Than the Sum of the Parts: Using Data Linkage and Cohort
      Designs to Create Data Synergy at MCHP.

PMID- 24933378
TI  - Taking It to the Streets: Figuring Out and Communicating What's Really Important
      in Children's Health and Well-being Research.

PMID- 24933379
TI  - Clinical Research at MCHP Over the Next 20 Years.

PMID- 24933380
TI  - Using administrative data to study child health.

PMID- 24933381
TI  - International health data linkage network.

PMID- 24933382
TI  - Dancing with the Media - Be Careful Not to Step on Your Partner's Toes: The
      Challenge of Working with the Media to Share Research Findings with the Public.

PMID- 24933383
TI  - Seeking the Balance between Harm and Benefit: The Role of Pharmacosurveillance in
      Choosing the Drugs We Should Take.

PMID- 24933384
TI  - Expanding the data repository: new technology and resources for the 21st century.

PMID- 24933385
TI  - Beyond administrative data: a vision for health information systems for Canada.

PMID- 24933386
TI  - The inside story: knowledge translation lessons from the need to know team.

PMID- 24933387
TI  - Healthcare services for an aging population: using administrative data to help
      prepare for the future.

PMID- 24933388
TI  - The effects of dietary counseling on children with food allergy: a prospective,
      multicenter intervention study.
AB  - Although dietary counseling is generally recommended in children with food
      allergy (FA), its effect on the nutritional status of these patients has not yet
      been evaluated. Our nonrandomized multicenter prospective intervention study was
      undertaken to investigate the effects of dietary counseling on children with FA.
      Anthropometric data, dietary intakes, and laboratory biomarkers of nutritional
      status were evaluated in children with FA (aged 6 to 36 months) before and after
      dietary counseling, by multidisciplinary teams composed of pediatricians,
      dietitians, and nurses. Ninety-one children with FA (49 boys and 42 girls; mean
      age 18.9 months, 95% CI 16.5 to 21.3) were evaluated; 66 children without FA (41
      boys and 25 girls; mean age 20.3 months, 95% CI 17.7 to 22.8) served as controls
      providing baseline values only. At enrollment, energy and protein intakes were
      lower in children with FA (91 kcal/kg/day, interquartile range [IQR]=15.1,
      minimum=55.2, maximum=130.6; and 2.2 g/kg/day, IQR=0.5, minimum=1.5, maximum=2.7,
      respectively) than in children without FA (96 kcal/kg/day, IQR=6.1, minimum=83.6,
      maximum=118.0; and 4.6 g/kg/day, IQR=1.2, minimum=2.0, maximum=6.1, respectively;
      P<0.001). A weight to length ratio <2 standard deviations was more frequent in
      children with FA than in children without FA (21% vs 3%; P<0.001). At 6 months
      following dietary counseling, the total energy intake of children with FA was
      similar to the baseline values of control children. Dietary counseling also
      resulted in a significant improvement of their anthropometric and laboratory
      biomarkers of nutritional status. The results of our study support the crucial
      role of dietary counseling in the clinical management of children with FA.

PMID- 24933390
TI  - Begging to be heard.

PMID- 24933389
TI  - Bifunctional chelates optimized for molecular MRI.
AB  - Important requirements for exogenous dyes or contrast agents in magnetic
      resonance imaging (MRI) include an effective concentration of paramagnetic or
      superparamagnetic ions at the target to be imaged. We report the concise
      synthesis and characterization of several new enantiopure bifunctional
      derivatives of (alpha(1)R,alpha(4)R,alpha(7)R,alpha(10)R)
      alpha(1),alpha(4),alpha(7),alpha(10)-tetramethyl-1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTMA) (and their 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTA) analogues as controls) that can be covalently
      attached to a contrast agent delivery system using either click or peptide
      coupling chemistry. Gd complexes of these derivatives can be attached to delivery
      systems while maintaining optimal water residence time for increased molecular
      imaging sensitivity. Long chain biotin (LC-biotin) derivatives of the Eu(III) and
      Gd(III) chelates associated with avidin are used to demonstrate higher
      efficiencies. Variable-temperature relaxometry, (17)O NMR, and nuclear magnetic
      resonance dispersion (NMRD) spectroscopy used on the complexes and biotin-avidin
      adducts measure the influence of water residence time and rotational correlation
      time on constrained and unconstrained systems. The Gd(III)-DOTMA derivative has a
      shorter water residence time than the Gd(III)-DOTA derivative. Compared to the
      constrained Gd(III)-DOTA derivatives, the rotationally constrained Gd(III)-DOTMA
      derivative has ~40% higher relaxivity at 37  degrees C, which could increase its
      sensitivity as an MRI agent as well as reduce the dose of the targeting agent. 

PMID- 24933392
TI  - Sequential EEG characteristics may predict seizure recurrence in rolandic
      epilepsy.
AB  - PURPOSE: The prognosis of rolandic epilepsy (RE) is considered favorable. Since a
      moderate proportion of cases presents with isolated seizures, continuous
      treatment should be considered only for frequent seizures. Clinical and
      electroencephalogram (EEG) markers to predict seizure recurrence need to be
      identified. The purpose of this study was to identify EEG criteria related to
      seizure recurrence in RE. METHODS: There were 10 children (aged 3-10 years; 6
      males, 4 females) in the recurrence group and 12 (aged 4-7 years; 6 males, 6
      females) in the isolated group. Occurrences of the number of spikes were scored,
      and the presence of rolandic discharges (RD) in the awake record was evaluated.
      All patients were evaluated longitudinally, clinically and by EEG, with repeated
      EEG recordings every 3 months. Clinical and EEG follow-up was performed for >=4
      years. RESULTS: Seizure recurrence and extended periods of high-frequency
      paroxysmal EEG abnormalities (>6 months after onset) were significantly
      correlated (p<0.001). Moreover, the appearance of RD in awake recordings tended
      to be more prevalent in the recurrence group than in the isolated group (odds
      ratio 4.714). CONCLUSION: In addition to RD in the awake record, a combination of
      spike rate and extended periods of high-frequency paroxysmal EEG abnormalities
      may predict seizure recurrence in RE.

PMID- 24933391
TI  - Solution structure of a bacterial microcompartment targeting peptide and its
      application in the construction of an ethanol bioreactor.
AB  - Targeting of proteins to bacterial microcompartments (BMCs) is mediated by an 18
      amino-acid peptide sequence. Herein, we report the solution structure of the N
      terminal targeting peptide (P18) of PduP, the aldehyde dehydrogenase associated
      with the 1,2-propanediol utilization metabolosome from Citrobacter freundii. The
      solution structure reveals the peptide to have a well-defined helical
      conformation along its whole length. Saturation transfer difference and
      transferred NOE NMR has highlighted the observed interaction surface on the
      peptide with its main interacting shell protein, PduK. By tagging both a pyruvate
      decarboxylase and an alcohol dehydrogenase with targeting peptides, it has been
      possible to direct these enzymes to empty BMCs in vivo and to generate an ethanol
      bioreactor. Not only are the purified, redesigned BMCs able to transform pyruvate
      into ethanol efficiently, but the strains containing the modified BMCs produce
      elevated levels of alcohol. 

PMID- 24933393
TI  - Cardiovascular pressure measurement in safety assessment studies: technology
      requirements and potential errors.
AB  - In the early days of in vivo nonclinical pressure measurement, most laboratories
      were required to have considerable technical/engineering expertise to configure
      and maintain pressure transducers, amplifiers, tape recorders, chart recorders,
      etc. Graduate students and postdoctoral fellows typically had some training in
      the requirements and limitations of the technology they used and were closely
      engaged in the collection and evaluation of data from their own experiments. More
      recently, pressure sensing telemetry and data acquisition/analysis systems are
      provided by vendors as turnkey systems, often resulting in a situation where
      users are less familiar with the technicalities of their operation. Also,
      investigators are now more likely to be absent and rely on technical staff for
      the collection of raw in vivo pressure data from their experiments than in the
      past. Depending on the goals of an experiment, an investigator may require the
      measurement of a variety of different pressure parameters, over varying periods
      of time. A basic understanding of the requirements and limitations that can
      affect the accuracy and precision of these parameters is important to ensure that
      the results and conclusions from an experiment are reliable. Factors to consider
      include the possibility of hydrostatic pressure effects from blood inside the
      vasculature of the animal, depending on the location of the sensor, as well as
      from fluid inside a fluid-filled catheter system; long-term stability (lack of
      drift) of a sensor over time, which can affect the interpretation of absolute
      pressure changes over a prolonged experiment; frequency response of the sensor
      and associated electronics; and the phase shift that occurs depending on location
      of the sensor in the vasculature or because of a fluid-filled catheter system.
      Each of these factors is discussed, and the particular requirements of frequency
      response as applied to the measurement of cardiac left ventricular pressure are
      emphasized. When these factors are understood, a pressure sensing and measurement
      system can be selected that is optimized for the experimental model being
      studied, thus eliminating errors or inaccurate results. 

PMID- 24933394
TI  - Alamar blue reagent interacts with cell-culture media giving different
      fluorescence over time: potential for false positives.
AB  - INTRODUCTION: The cell viability assay by alamar blue is based on the principle
      of reduction of the non-fluorescent reagent (resazurin) to a fluorescent compound
      (resarufin) by the intracellular reducing environment of living cells over time.
      In the present study, we have for the first time shown that even in the absence
      of cells, there occurs significant interaction between alamar blue and cell
      culture media causing an increase in fluorescence. METHODS: We have used Opti
      MEM, DMEM and 1:1 DMEM:Opti-MEM as three different media and determined the
      changes in their relative fluorescence units (RFUs) over time after the addition
      of 10% (v/v) alamar blue using two-way repeated measures analysis of variance (RM
      ANOVA) followed by Tukey's post-hoc test. RESULTS: Our results show that upon the
      addition of alamar blue, there occurs a significant increase in RFUs in all the
      three media over time along with a significantly higher RFU for the Opti-MEM
      overall (p<0.05). We also show that the time-dependent change in RFU of 1:1
      DMEM:Opti-MEM was more gradual compared to that of the other two media.
      DISCUSSION: These findings indicate that the reagent can itself interact with the
      media causing significantly different fluorescence over time in a manner
      independent from the effect of intracellular reducing environment of living cells
      on alamar blue. In addition our results indicate that fluorescence varies as a
      function of incubation time with the reagent. These findings signify the need for
      routine subtraction of the background fluorescence of media-only with alamar blue
      reagent during measurement of cell viability by this method in order to determine
      an accurate measurement of cell viability.

PMID- 24933395
TI  - A multiple microwave ablation strategy in patients with initially unresectable
      colorectal cancer liver metastases - A safety and feasibility study of a new
      concept.
AB  - AIMS: Resection for colorectal cancer liver metastases is indicated when an R0
      resection with preservation of a sufficient future liver remnant (FLR) is
      achievable. Multimodality conversion of initially unresectable patients to
      resectable is possible in some patients. We present results of a downstaging
      strategy using microwave ablation (MWA). PATIENTS AND METHODS: In patients where
      resection was precluded by absence of a tumour-free FLR due to the extent of
      segmental tumour engagement, but with the potential to clear the whole liver with
      multiple local ablations, MWA was performed at laparotomy using ultrasound
      guidance or computer-assisted navigation. Mortality and morbidity was recorded
      and the overall and disease-free survival of the ablated patients was compared to
      data of two historic cohorts. RESULTS: Ten of twenty treated patients were alive
      at median follow-up 25 months. There was no perioperative mortality, with MWA
      associated complications being mild to moderate. The MWA group showed a 4-year
      overall survival of 41%, compared to 70% for a historic cohort of primarily
      resected patients and 4% for patients with palliative treatment. CONCLUSION:
      Results of the multiple ablation strategy in the defined population suggest a
      survival benefit, compared to palliative chemotherapy alone with acceptable
      associated morbidity and no perioperative mortality.

PMID- 24933397
TI  - Structure-property relationships of curved aromatic materials from first
      principles.
AB  - CONSPECTUS: Considerable effort in the past decade has been extended toward
      achieving computationally affordable theoretical methods for accurate prediction
      of the structure and properties of materials. Theoretical predictions of solids
      began decades ago, but only recently have solid-state quantum techniques become
      sufficiently reliable to be routinely chosen for investigation of solids as
      quantum chemistry techniques are for isolated molecules. Of great interest are ab
      initio predictive theories for solids that can provide atomic scale insights into
      properties of bulk materials, interfaces, and nanostructures. Adaption of the
      quantum chemical framework is challenging in that no single theory exists that
      provides prediction of all observables for every material type. However, through
      a combination of interdisciplinary efforts, a richly textured and substantive
      portfolio of methods is developing, which promise quantitative predictions of
      materials and device properties as well as associated performance analysis.
      Particularly relevant for device applications are organic semiconductors (OSC),
      with electrical conductivity between that of insulators and that of metals.
      Semiconducting small molecules, such as aromatic hydrocarbons, tend to have high
      polarizabilities, small band-gaps, and delocalized pi electrons that support
      mobile charge carriers. Most importantly, the special nature of optical
      excitations in the form of a bound electron-hole pairs (excitons) holds
      significant promise for use in devices, such as organic light emitting diodes
      (OLEDs), organic photovoltaics (OPVs), and molecular nanojunctions. Added
      morphological features, such as curvature in aromatic hydrocarbon structure, can
      further confine the electronic states in one or more directions leading to
      additional physical phenomena in materials. Such structures offer exploration of
      a wealth of phenomenology as a function of their environment, particularly due to
      the ability to tune their electronic character through functionalization. This
      Account offers discussion of current state-of-the-art electronic structure
      approaches for prediction of structural, electronic, optical, and transport
      properties of materials, with illustration of these capabilities from a series of
      investigations involving curved aromatic materials. The class of curved aromatic
      materials offers the ability to investigate methodology across a wide range of
      materials complexity, including (a) molecules, (b) molecular crystals, (c)
      molecular adsorbates on metal surfaces, and (d) molecular nanojunctions. A
      reliable pallet of theoretical tools for such a wide array relies on expertise
      spanning multiple fields. Working together with experimental experts,
      advancements in the fundamental understanding of structural and dynamical
      properties are enabling focused design of functional materials. Most importantly,
      these studies provide an opportunity to compare experimental and theoretical
      capabilities and open the way for continual improvement of these capabilities.

PMID- 24933396
TI  - Risk pathways among traumatic stress, posttraumatic stress disorder symptoms, and
      alcohol and drug problems: a test of four hypotheses.
AB  - The present study utilized longitudinal data from a community sample (n = 377;
      166 trauma-exposed; 54% males; 73% non-Hispanic Caucasian; 22% Hispanic; 5% other
      ethnicity) to test whether pretrauma substance use problems increase risk for
      trauma exposure (high-risk hypothesis) or posttraumatic stress disorder (PTSD)
      symptoms (susceptibility hypothesis), whether PTSD symptoms increase risk for
      later alcohol/drug problems (self-medication hypothesis), and whether the
      association between PTSD symptoms and alcohol/drug problems is attributable to
      shared risk factors (shared vulnerability hypothesis). Logistic and negative
      binomial regressions were performed in a path analysis framework. Results
      provided the strongest support for the self-medication hypothesis, such that PTSD
      symptoms predicted higher levels of later alcohol and drug problems, over and
      above the influences of pretrauma family risk factors, pretrauma substance use
      problems, trauma exposure, and demographic variables. Results partially supported
      the high-risk hypothesis, such that adolescent substance use problems increased
      risk for assaultive violence exposure but did not influence overall risk for
      trauma exposure. There was no support for the susceptibility hypothesis. Finally,
      there was little support for the shared vulnerability hypothesis. Neither trauma
      exposure nor preexisting family adversity accounted for the link between PTSD
      symptoms and later substance use problems. Rather, PTSD symptoms mediated the
      effect of pretrauma family adversity on later alcohol and drug problems, thereby
      supporting the self-medication hypothesis. These findings make important
      contributions to better understanding the directions of influence among traumatic
      stress, PTSD symptoms, and substance use problems.

PMID- 24933398
TI  - Adiponectin is associated with increased mortality in patients with already
      established cardiovascular disease: a systematic review and meta-analysis.
AB  - BACKGROUND: The overall quantitative estimate on the possible association of
      adiponectin concentrations with mortality in patients with cardiovascular
      diseases (CVD) has not been reported. METHODS: We performed a systematic review
      and meta-analysis of prospective studies to evaluate the overall quantitative
      estimates on the adiponectin levels for risk of mortality in patients with CVD.
      MEDLINE, EMBASE, CINAHL, and the Cochrane Library (up to Mar 22, 2014) were used
      to search for studies evaluating the effect of adiponectin levels on mortality in
      patients with CVD. Random-effect models were selected to estimate overall effect
      estimates. RESULTS: Data from 14063 CVD patients enrolled in 15 prospective
      cohort and 1 nested case control studies were collated. The meta-analyses showed
      strong positive association of adiponectin with all-cause (n=14 studies, overall
      pooled effect estimate=1.45 [95% CI, 1.17-1.79]) and cardiovascular (n=11
      studies, overall pooled effect estimate=1.69 [1.35-2.10]) mortality, for the
      highest tertile of adiponectin levels versus the lowest tertile. Subgroup
      analyses show study characteristics (including effect estimate, mean age, study
      location, sample sizes, gender, durations of follow-up, types of primary event,
      and acute or chronic CVD) did not substantially influence these positive
      associations. CONCLUSIONS: Our results showed that increased baseline plasma
      adiponectin levels are significantly associated with elevated risk of all-cause
      and cardiovascular mortality in subjects with CVD. These positive associations
      may have been amplified by adjustment for potential intermediates or residual
      confounding, and their basis requires further investigation.

PMID- 24933399
TI  - Exendin-4 regulates lipid metabolism and fibroblast growth factor 21 in hepatic
      steatosis.
AB  - OBJECTIVE: Hepatokine fibroblast growth factor (FGF) 21 takes part in the
      regulation of lipid metabolism in the liver and adipose tissue. We investigated
      whether exendin-4 regulates the expression of FGF21 in the liver, and whether the
      effects of exendin-4 on the regulation of FGF21 expression are mediated via
      silent mating type information regulation 2 homolog (SIRT) 1 or SIRT6.
      MATERIALS/METHODS: The C57BL/6J mice were fed a low fat diet, high fat diet, or
      high fat diet with 1 nmol/kg/day exendin-4 intraperitoneal injection for 10
      weeks. HepG2 used in vitro study was treated with palmitic aicd (0.4 mM) with or
      without exendin-4 (100 nM) and FGF21 (50 nM) for 24 hours. The change of FGF21
      and its receptors expression by exendin-4 were measured using quantitative real
      time RT-PCR and Western blot. The intracellular lipid content in HepG2 cells was
      evaluated by Oil Red O staining. Inhibition of FGF21, SIRT1 and SIRT6, by 10 nM
      siRNA was performed to establish the signaling pathway of exendin-4 action in
      hepatic lipid metabolism. RESULTS: Exendin-4 increased the expression of FGF21
      and its receptors in high fat diet-induced obese mice. In addition, recombinant
      FGF21 treatment reduced lipid content in palmitic acid-treated HepG2 cells. We
      also observed significantly decreased expression of peroxisomal proliferator
      activated receptor (PPAR) alpha and medium-chain acyl-coenzyme A dehydrogenase
      (MCAD) in hepatocytes transfected with FGF21 siRNA. In cells treated with exendin
      4, inhibition of SIRT1, but not SIRT6, by siRNA significantly repressed the
      expression of FGF21 mRNA, whereas decreased SIRT1 expression by inhibition of
      FGF21 was not observed. CONCLUSIONS: These data suggest that exendin-4 could
      improve fatty liver by increasing SIRT1-mediated FGF21.

PMID- 24933401
TI  - Childhood adversities and adolescent depression: a matter of both risk and
      resilience.
AB  - Childhood adversities have been proposed to modify later stress sensitivity and
      risk of depressive disorder in several ways: by stress sensitization, stress
      amplification, and stress inoculation. Combining these models, we hypothesized
      that childhood adversities would increase risk of early, but not later, onsets of
      depression (Hypothesis 1). In those without an early onset, childhood adversities
      were hypothesized to predict a relatively low risk of depression in high-stress
      conditions (Hypothesis 2a) and a relatively high risk of depression in low-stress
      conditions (Hypothesis 2b), compared to no childhood adversities. These
      hypotheses were tested in 1,584 participants of the Tracking Adolescents'
      Individual Lives Survey, a prospective cohort study of adolescents. Childhood
      adversities were assessed retrospectively at ages 11 and 13.5, using self-reports
      and parent reports. Lifetime DSM-IV major depressive episodes were assessed at
      age 19, by means of the Composite International Diagnostic Interview. Stressful
      life events during adolescence were established using interview-based contextual
      ratings of personal and network events. The results provided support for all
      hypotheses, regardless of the informant and timeframe used to assess childhood
      adversities and regardless of the nature (personal vs. network, dependent vs.
      independent) of recent stressful events. These findings suggest that age at first
      onset of depression may be an effective marker to distinguish between various
      types of reaction patterns. 

PMID- 24933400
TI  - Dipeptidyl peptidase inhibition prevents diastolic dysfunction and reduces
      myocardial fibrosis in a mouse model of Western diet induced obesity.
AB  - OBJECTIVE: Consumption of a high-fat/high-fructose Western diet (WD) is linked to
      rising obesity and heart disease, particularly diastolic dysfunction which
      characterizes early obesity/metabolic cardiomyopathy. Mounting evidence supports
      a role for inflammation, oxidative stress and fibrosis in the pathophysiology of
      metabolic cardiomyopathy. Dipeptidyl peptidase-4 (DPP-4) is a circulating
      exopeptidase recently reported to be elevated in the plasma of patients with
      insulin resistance (IR), obesity and heart failure. We hypothesized that a model
      of WD induced obesity/metabolic cardiomyopathy would exhibit increased DPP-4
      activity and cardiac fibrosis with DPP-4 inhibition preventing cardiac fibrosis
      and the associated diastolic dysfunction. MATERIALS/METHODS: Four-week-old
      C57BL6/J mice were fed a high-fat/high-fructose WD with the DPP-4 inhibitor
      MK0626 for 16 weeks. Cardiac function was examined by high-resolution cine
      cardiac magnetic resonance imaging (MRI). Phenotypic analysis included
      measurements of body and heart weight, systemic IR and DPP-4 activity.
      Immunohistochemistry and transmission electron microscopy (TEM) were utilized to
      identify underlying pathologic mechanisms. RESULTS: We found that chronic WD
      consumption caused obesity, IR, elevated plasma DPP-4 activity, heart enlargement
      and diastolic dysfunction. DPP-4 inhibition with MK0626 in WD fed mice resulted
      in >75% reduction in plasma DPP-4 activity, improved IR and normalized diastolic
      relaxation. WD consumption induced myocardial oxidant stress and fibrosis with
      amelioration by MK0626. TEM of hearts from WD fed mice revealed abnormal
      mitochondrial and perivascular ultrastructure partially corrected by MK0626.
      CONCLUSIONS: This study provides evidence of a role for increased DPP-4 activity
      in metabolic cardiomyopathy and a potential role for DPP-4 inhibition in
      prevention and/or correction of oxidant stress/fibrosis and associated diastolic
      dysfunction.

PMID- 24933402
TI  - Facilitating classroom based interprofessional learning: a grounded theory study
      of university educators' perceptions of their role adequacy as facilitators.
AB  - The provision of inter professional learning (IPL) within undergraduate
      programmes is now well established within many Higher Education Institutions
      (HEIs). IPL aims to better equip nurses and other health professionals with
      effective collaborative working skills and knowledge to improve the quality of
      patient care. Although there is still ambiguity in relation to the optimum timing
      and method for delivering IPL, effective facilitation is seen as essential. This
      paper reports on a grounded theory study of university educators' perceptions of
      the knowledge and skills needed for their role adequacy as IPL facilitators. Data
      was collected using semi structured interviews with nine participants who were
      theoretically sampled from a range of professional backgrounds, with varied
      experiences of education and involvement in facilitating IPL. Constant
      comparative analysis was used to generate four data categories: creating and
      sustaining an IPL group culture through transformational IPL leadership (core
      category), readiness for IPL facilitation, drawing on past interprofessional
      learning and working experiences and role modelling an interprofessional
      approach. The grounded theory generated from this study, although propositional,
      suggests that role adequacy for IPL facilitation is dependent on facilitator
      engagement in a process of 'transformational interprofessional learning
      leadership' to create and sustain a group culture. 

PMID- 24933403
TI  - Wide temperature range testing with ROTEM coagulation analyses.
AB  - Mild induced hypothermia is used for neuroprotection in patients successfully
      resuscitated after cardiac arrest. Temperature-dependent effects on rotational
      thromboelastometry (ROTEM((r))) assays with EXTEM((r)), FIBTEM((r)), or
      APTEM((r)) in cardiac arrest patients have not previously been studied. Ten
      patients with out-of-hospital cardiac arrest who underwent induced hypothermia
      were studied during stable hypothermia at 33 degrees C. ROTEM temperature effects
      on EXTEM, FIBTEM, and APTEM assays were studied at temperatures set between 30
      degrees C and 42 degrees C. Citrated whole blood test tubes were incubated in
      temperature-adjusted heating blocks and then investigated at respective
      temperature in the temperature-adjusted ROTEM. The following variables were
      determined: clotting time (CT), clot formation time (CFT), alpha-angle, and
      maximum clot firmness (MCF). The results from hypo- and hyperthermia samples were
      compared with the samples incubated at 37 degrees C using the Wilcoxon matched
      pairs signed-rank test. A p-value of <0.05 was considered significant. CT
      EXTEM((r)) and CT-APTEM((r)) were prolonged by hypothermia at 30 degrees C
      (p<0.01 for both) and 33 degrees C (p<0.05 for both). Hyperthermia at 42 degrees
      C shortened CT-EXTEM (p<0.05) and CT-APTEM (p<0.01). CFT-EXTEM((r)) and CFT
      APTEM((r)) were markedly prolonged by hypothermia at 30 degrees C, 33 degrees C,
      and 35 degrees C (p<0.01 for all except CFT-EXTEM, 35 degrees C [p<0.05]). The
      alpha-angle-EXTEM was markedly decreased at 30 degrees C, 33 degrees C, and 35
      degrees C (p<0.01) but increased at 40 degrees C (p<0.05) and 42 degrees C
      (p<0.01); alpha-angle-APTEM showed similar results. MCF was unchanged at
      different temperatures for all tests. ROTEM (EXTEM, FIBTEM, and APTEM assays)
      revealed a hypocoagulative response to in vitro-applied hypothermia in the blood
      of cardiac arrest patients reflected in the prolonged clot initiation and
      decreased clot propagation. Hyperthermia showed the opposite effects. Clot
      firmness was not affected by temperature. 

PMID- 24933405
TI  - Design of highly sensitive and selective Au@NiO yolk-shell nanoreactors for gas
      sensor applications.
AB  - Au@NiO yolk-shell nanoparticles (NPs) were synthesized by simple solution route
      and applied for efficient gas sensor towards H2S gas. Carbon encapsulated Au
      (Au@C core-shell) NPs were synthesized by glucose-assisted hydrothermal method,
      whereas Au@NiO yolk-shell NPs were synthesized by precipitation method using Au@C
      core-shell NPs as a template. Sub-micrometer Au@NiO yolk-shell NPs were formed
      having 50-70 nm Au NPs at the periphery of NiO shell (10-20 nm), which was
      composed of 6-12 nm primary NiO particles. Au@NiO yolk-shell NPs showed higher
      response for H2S compared to other interfering gases (ethanol, p-xylene, NH3, CO
      and H2). The maximum response was 108.92 for 5 ppm of H2S gas at 300  degrees C,
      which was approximately 19 times higher than that for the interfering gases. The
      response of Au@NiO yolk-shell NPs to H2S was approximately 4 times higher than
      that of bare NiO hollow nanospheres. Improved performance of Au@NiO yolk-shell
      NPs was attributed to hollow spaces that allowed the accessibility of Au NPs to
      gas molecules. It was suggested that adsorption of H2S on Au NPs resulted in the
      formation of sulfide layer, which possibly lowered its work function, and
      therefore tuned the electron transfer from Au to NiO rather NiO to Au, which
      leaded to increase in resistance and therefore response.

PMID- 24933404
TI  - External validation of the SF-36 quality-of-life questionnaire in Italian and
      Brazilian populations to select patients with colorectal endometriosis for
      surgery.
AB  - STUDY OBJECTIVE: To evaluate the external validity of the validated French model
      of the quality-of-life questionnaire (QOL) SF-36 in predicting improvement after
      colorectal resection for endometriosis. DESIGN: Italian and Brazilian cohort
      studies (Canadian Task Force classification II-3). SETTING: Tertiary referral
      university hospital in Brazil and expert center in endometriosis in Italy.
      PATIENTS: Patients with colorectal endometriosis from an Italian population (n =
      63) and a Brazilian population (n = 151). INTERVENTION: Laparoscopic colorectal
      resection for treatment of endometriosis. MEASUREMENTS AND MAIN RESULTS:
      Preoperative and postoperative evaluations of the Physical Component Summary
      (PCS) and the Mental Component Summary (MCS) of the SF-36 were performed.
      Substantial improvement in PCS and MCS was observed after colorectal resection in
      both populations. In the Brazilian population, the receiver operating curve (ROC)
      (area under the curve [AUC]) was 0.83 (95% confidence interval [CI], 0.77-0.89)
      for MCS and 0.78 (95% CI, 0.71-0.83) for PCS, demonstrating good discrimination
      performance. The mean difference between the predicted and calibrated
      probabilities was 19.6% for MCS and 32.8% for PCS. In the Italian population, the
      ROC curve (AUC) was 0.65 (95% CI, 0.52-0.78) for PCS and 0.67 (95% CI, 0.55-0.78)
      for MCS. The model demonstrated poor discrimination and calibration performance
      for PCS (p < .001) and MCS (p = .003). The mean difference between the predicted
      and calibrated probabilities was 17.5% for MCS and 21.8% for PCS. CONCLUSION:
      Despite the use of validated translations of the SF-36, our results underline the
      limits of this tool in selection of patients for colorectal resection due to
      underestimation of predicted quality of life, possibly because of variations in
      epidemiologic characteristics of the populations.

PMID- 24933406
TI  - Characterization of titanium dioxide nanoparticles in food products: analytical
      methods to define nanoparticles.
AB  - Titanium dioxide (TiO2) is a common food additive used to enhance the white
      color, brightness, and sometimes flavor of a variety of food products. In this
      study 7 food grade TiO2 materials (E171), 24 food products, and 3 personal care
      products were investigated for their TiO2 content and the number-based size
      distribution of TiO2 particles present in these products. Three principally
      different methods have been used to determine the number-based size distribution
      of TiO2 particles: electron microscopy, asymmetric flow field-flow fractionation
      combined with inductively coupled mass spectrometry, and single-particle
      inductively coupled mass spectrometry. The results show that all E171 materials
      have similar size distributions with primary particle sizes in the range of 60
      300 nm. Depending on the analytical method used, 10-15% of the particles in these
      materials had sizes below 100 nm. In 24 of the 27 foods and personal care
      products detectable amounts of titanium were found ranging from 0.02 to 9.0 mg
      TiO2/g product. The number-based size distributions for TiO2 particles in the
      food and personal care products showed that 5-10% of the particles in these
      products had sizes below 100 nm, comparable to that found in the E171 materials.
      Comparable size distributions were found using the three principally different
      analytical methods. Although the applied methods are considered state of the art,
      they showed practical size limits for TiO2 particles in the range of 20-50 nm,
      which may introduce a significant bias in the size distribution because particles
      <20 nm are excluded. This shows the inability of current state of the art methods
      to support the European Union recommendation for the definition of nanomaterials.

PMID- 24933407
TI  - Coagulation and transfusion in the postoperative bleeding patient.
AB  - PURPOSE OF REVIEW: Bleeding can be minimal, severe, life-threatening, or organ
      threatening. Depending on the compensatory capacity of the patient, most bleeding
      events going beyond 20% blood volume may represent an emergency as well as a risk
      factor for anemia, transfusion, coagulopathy, and tissue hypoperfusion. All these
      factors are independent predictors for survival in postoperative critical care
      and are drivers for resource use and costs. RECENT FINDINGS: A systematic
      literature search behind the guidelines from the European Society of
      Anesthesiology on the management of severe perioperative bleeding gives an up-to
      date evidence-based summary of strategies intended to correct hemostasis, control
      bleeding, and increase patient safety. The current review discusses information,
      recommendations, and suggestions in the European Society of Anesthesiology
      guidelines, which appear applicable to the bleeding patient after the end of
      surgery. SUMMARY: Individualized coagulation management guided by viscoelastic
      tests and restrictive transfusion behavior are encouraged in clinical practice of
      critical care. Potential fields of research are multifold, for example,
      thromboembolic adverse effects of hemostatic interventions in the isochronic
      postoperative acute-phase response, transfusion restrictions by increasing
      postoperative tolerance to anemia and erythropoiesis, and implementation of
      guidelines and institutional algorithms.

PMID- 24933408
TI  - Approach-Avoidance Attitudes Associated with Initial Therapy Appointment
      Attendance: A Prospective Study.
AB  - BACKGROUND: Initial therapy appointments have high nonattendance rates yet the
      reasons remain poorly understood. AIMS: This study aimed to identify positive and
      negative attitudes towards therapy that predicted initial attendance, informed by
      a perceptual control theory account of approach-avoidance conflicts in help
      seeking. METHOD: A prospective study was conducted within a low intensity CBT
      service using first appointment attendance (n = 96) as an outcome. Measures
      included attitudes towards therapy, depression and anxiety scales, and
      demographic variables. RESULTS: Endorsement of a negative attitude item
      representing concern about self-disclosure was independently predictive of
      nonattendance. Positive attitudes predicted increased attendance, especially
      endorsement of motives for self-reflection, but only among less depressed
      individuals. CONCLUSIONS: Self-disclosure concerns contribute to therapy
      avoidance and having goals for self-reflection may represent approach motivation
      for therapy; however, the latter has less impact among more highly depressed
      people.

PMID- 24933409
TI  - Synthesis, hybridization characteristics, and fluorescence properties of
      oligonucleotides modified with nucleobase-functionalized locked nucleic acid
      adenosine and cytidine monomers.
AB  - Conformationally restricted nucleotides such as locked nucleic acid (LNA) are
      very popular as affinity-, specificity-, and stability-enhancing modifications in
      oligonucleotide chemistry to produce probes for nucleic acid targeting
      applications in molecular biology, biotechnology, and medicinal chemistry.
      Considerable efforts have been devoted in recent years to optimize the
      biophysical properties of LNA through additional modification of the sugar
      skeleton. We recently introduced C5-functionalization of LNA uridines as an
      alternative and synthetically more straightforward approach to improve the
      biophysical properties of LNA. In the present work, we set out to test the
      generality of this concept by studying the characteristics of oligonucleotides
      modified with four different C5-functionalized LNA cytidine and C8-functionalized
      LNA adenosine monomers. The results strongly suggest that C5-functionalization of
      LNA pyrimidines is indeed a viable approach for improving the binding affinity,
      target specificity, and/or enzymatic stability of LNA-modified ONs, whereas C8
      functionalization of LNA adenosines is detrimental to binding affinity and
      specificity. These insights will impact the future design of conformationally
      restricted nucleotides for nucleic acid targeting applications. 

PMID- 24933410
TI  - Quantitative EEG in Alzheimer's disease: cognitive state, resting state and
      association with disease severity.
AB  - BACKGROUND: Quantitative electroencephalogram (qEEG) recorded during cognitive
      tasks has been shown to differentiate between patients with Alzheimer's disease
      (AD) and healthy individuals. However, the association between various qEEG
      markers recorded during mnestic paradigms and clinical measures of AD has not
      been studied in detail. OBJECTIVE: To evaluate if 'cognitive' qEEG is a useful
      diagnostic option, particularly if memory paradigms are used as cognitive
      stimulators. METHODS: This study is part of the Prospective Registry on Dementia
      in Austria (PRODEM), a multicenter dementia research project. A cohort of 79
      probable AD patients was included in a cross-sectional analysis. qEEG recordings
      performed in resting states were compared with recordings during cognitively
      active states. Cognition was evoked with a face-name paradigm and a paired
      associate word list task, respectively. Relative band powers, coherence and auto
      mutual information were computed as functions of MMSE scores for the memory
      paradigms and during rest. Analyses were adjusted for the co-variables age, sex,
      duration of dementia and educational level. RESULTS: MMSE scores explained 36-51%
      of the variances of qEEG-markers. Face-name encoding with eyes open was superior
      to resting state with eyes closed in relative theta and beta1 power as well as
      coherence, whereas relative alpha power and auto-mutual information yielded more
      significant results during resting state with eyes closed. The face-name task
      yielded stronger correlations with MMSE scores than the verbal memory task.
      CONCLUSION: qEEG alterations recorded during mnestic activity, particularly face
      name encoding showed the highest association with the MMSE and may serve as a
      clinically valuable marker for disease severity.

PMID- 24933412
TI  - Credibility assessment: preliminary process theory, the polygraph process, and
      construct validity.
AB  - The term "polygraph test," particularly in a forensic context, is used generally
      to describe diagnostic procedures using a polygraph instrument to assess
      credibility. Polygraph testing has been subject to greater scrutiny, debate, and
      empirical study than many other forensic techniques. It has been repeatedly
      demonstrated that, when used properly, the polygraph testing process functions
      with a high degree of predictive (criterion) validity. However, advocates have
      failed to address, in a substantive manner, the primary objection often cited by
      opponents that the polygraph procedure most used in applied day-to-day contexts,
      that is, Comparison Question Testing (CQT), is atheoretical and lacking construct
      validity. A review of the available research literature, including that from the
      neurosciences, psychophysiology, and other relevant disciplines, coupled with an
      intimate understanding of two commonly used polygraph procedures, the context in
      which they are used, and the scientific method, strongly suggests that such
      claims are no longer true, nor warranted. Here, we discuss the interplay of the
      two most advocated polygraph procedures, the CQT and CIT (Concealed Information
      Testing), with Preliminary Process Theory (PPT), contemporary writings on memory
      and other contributions from the research literature relevant to the instrumental
      assessment of credibility. We conclude that the available scientific evidence not
      only establishes a plausible theoretical construct that strengthens the practical
      application of the polygraph process in forensic and other settings, but also
      concurrently provides directions for future research by scientists interested in
      the applied assessment of credibility. 

PMID- 24933411
TI  - Infant cortical electrophysiology and perception of vowel contrasts.
AB  - Cortical auditory evoked potentials (CAEPs) were obtained for vowel tokens
      presented in an oddball stimulus paradigm. Perceptual measures of vowel
      discrimination were obtained using a visually-reinforced head-turn paradigm. The
      hypothesis was that CAEP latencies and amplitudes would differ as a function of
      vowel type and be correlated with perceptual performance. Twenty normally hearing
      infants aged 4-12 months were evaluated. CAEP component amplitudes and latencies
      were measured in response to the standard, frequent token /a/ and for infrequent,
      deviant tokens /i/, /o/ and /u/, presented at rates of 1 and 2 tokens/s. The
      perceptual task required infants to make a behavioral response for trials that
      contained two different vowel tokens, and ignore those in which the tokens were
      the same. CAEP amplitudes were larger in response to the deviant tokens, when
      compared to the control condition in which /a/ served as both standard and
      deviant. This was also seen in waveforms derived by subtracting the response to
      standard /a/ from the responses to deviant tokens. CAEP component latencies in
      derived responses at 2/s also demonstrated some sensitivity to vowel contrast
      type. The average hit rate for the perceptual task was 68.5%, with a 25.7% false
      alarm rate. There were modest correlations of CAEP amplitudes and latencies with
      perceptual performance. The CAEP amplitude differences for vowel contrasts could
      be used as an indicator of the underlying neural capacity to encode spectro
      temporal differences in vowel sounds. This technique holds promise for
      translation to clinical methods for evaluating speech perception.

PMID- 24933413
TI  - The visual mismatch negativity (vMMN): toward the optimal paradigm.
AB  - In the present article, we tested an optimal vMMN paradigm allowing one to obtain
      vMMNs for several visual attributes in a short time. vMMN responses to changes in
      color, duration, orientation, shape, and size were compared between the
      traditional 'oddball' paradigm (a single type of visual change in each sequence)
      and the optimal paradigm in which all the 5 types of changes appeared within the
      same sequence. The vMMNs obtained in the optimal paradigm were equal or larger in
      amplitude to those in the traditional vMMN paradigm. The optimal paradigm can
      provide 5 different vMMNs in the same time in which usually only one MMN is
      obtained. This short objective measure could putatively be used as an index for
      visual cognition function especially in clinical research. 

PMID- 24933414
TI  - SIAMO: Italian Pediatric Oncologists and Adult Medical Oncologists Join Forces
      for Adolescents with Cancer.

PMID- 24933416
TI  - Is living with psychosis demoralizing? Insight, self-stigma, and clinical outcome
      among people with schizophrenia across 1 year.
AB  - Lack of insight is a major target in the treatment of schizophrenia. However,
      insight may have undesirable effects on self-concept and motivation that can
      hinder recovery. This study aimed to examine the link between insight, self
      stigma, and demoralization as predictors of symptoms and functioning. Insight,
      self-stigma, depressive and psychotic symptoms, and functioning were assessed
      among 133 outpatients with schizophrenia at baseline and 12 months later. The
      data were analyzed by hierarchical multiple linear regressions. More insight at
      baseline and an increase in self-stigma over 12 months predicted more
      demoralization at follow-up. Insight at baseline was not associated with any
      outcome variable, but self-stigma at baseline was related to poorer functioning
      and more positive symptoms at follow-up. More demoralization at baseline
      predicted poorer functioning 12 months later. Demoralization did not mediate the
      relationship between self-stigma at baseline and functioning after 1 year. Given
      the decisive role of self-stigma regarding recovery from schizophrenia,
      dysfunctional beliefs related to illness and the self should be addressed in
      treatment. Different psychotherapeutical approaches are discussed. 

PMID- 24933415
TI  - Psychiatrists' views of the genetic bases of mental disorders and behavioral
      traits and their use of genetic tests.
AB  - We examined how 372 psychiatrists view genetic aspects of mental disorders and
      behaviors and use genetic tests (GTs). Most thought that the genetic contribution
      was moderate/high for bipolar disorder, schizophrenia, depression, Alzheimer's,
      intelligence, creativity, anxiety, and suicidality. In the past 6 months, 14.1%
      ordered GTs, 18.3% discussed prenatal testing with patients, 36.0% initiated
      discussions about other GTs, 41.6% had patients ask about GTs, and 5.3% excluded
      GT results from patient records. Many thought that GTs; were available for
      schizophrenia (24.3%) and major depression (19.6%). Women were more likely to
      report that patients asked about GTs; and were less certain about the degree of
      genetic contribution to several disorders. Psychiatrists perceive strong genetic
      bases for numerous disorders and traits, and many have discussed and ordered
      tests for GTs, but have relatively limited knowledge about available tests. These
      data suggest possible sex differences in psychiatrists' beliefs about genetic
      contributions to disorders and have implications for future research, education,
      policy, and care. 

PMID- 24933417
TI  - Perceptual properties of obsessive thoughts are associated with low insight in
      obsessive-compulsive disorder.
AB  - Obsessions are traditionally defined as bothersome and repetitive thoughts that
      the patient is unable to resist. Preliminary evidence suggests that in a subgroup
      of patients with obsessive-compulsive disorder (OCD), obsessions are experienced
      as partially perceptual. The present study explored the frequency of perceptually
      laden obsessions and their relationship with illness insight and depression.
      Twenty-six patients with OCD were administered the newly developed Sensory
      Properties of Obsessions Questionnaire. Participants were asked to endorse on a 5
      point Likert scale whether their obsessions were associated with perceptual
      features. Participants showed moderate symptom severity. A total of 73% affirmed
      that their obsessions contained perceptual features. The predominant perceptual
      channels were visual, tactile, and somatic (i.e., bodily sensations). The extent
      of perceptual aspects associated with obsessions was strongly correlated with
      lack of insight (Yale-Brown Obsessive-Compulsive Scale item 11) but not
      depression severity. The present study suggests that obsessive thoughts are
      frequently accompanied by perceptual sensations, which concurs with models
      assuming a continuum between hallucinations and intrusions. Apparently, the more
      "real" or authentic the obsessive thought is experienced, the less the afflicted
      person is able to dismiss its content as fully irrational or absurd. 

PMID- 24933418
TI  - Surfactant selection principle for reducing critical micelle concentration in
      mixtures of oppositely charged gemini surfactants.
AB  - Cationic quaternary ammonium gemini surfactants
      C(n)H(2n+1)(CH3)2N(+)CH2CHCHCH2(CH3)2N(+)C(n)H(2n+1)2Br(-) (C(n)C4C(n), n = 12,
      8, 6) with alkyl spacers,
      C(n)H(2n+1)(CH3)2N(+)CH2CHOHCHOHCH2(CH3)2N(+)C(n)H(2n+1)2Br(-) (C(n)C4(OH)2C(n),
      n = 12, 8, 6, 4) with two hydroxyl groups in alkyl spacers, and cationic ammonium
      single-chain surfactants C(n)H(2n+1)(CH3)2N(+)Br(-) (C(n)TAB, n = 12, 8, 6) have
      been chosen to fabricate oppositely charged surfactant mixtures with anionic
      sulfonate gemini surfactant C12H25N(CH2CH2CH2SO3(
      ))CH2CH2CH2(CH3)2N(CH2CH2CH2SO3(-))C12H252Na (C12C3C12(SO3)2). Surface tension,
      electrical conductivity, and isothermal titration microcalorimetry (ITC) were
      used to study their surface properties, aggregation behaviors, and intermolecular
      interactions. The mixtures of C12C3C12(SO3)2/C(n)C4(OH)2C(n) (n = 12, 8) and
      C12C3C12(SO3)2/C12C4C12 show anomalous larger critical micelle concentration
      (CMC) than C12C3C12(SO3)2, while the mixtures of C12C3C12(SO3)2/C(n)C4(OH)2C(n)
      (n = 6, 4), C12C3C12(SO3)2/C(n)C4(OH)2C(n) (n = 6, 4), and C12C3C12(SO3)2/C(n)TAB
      (n = 12, 8, 6) exhibit much lower CMC than C12C3C12(SO3)2. The results indicate
      that strong hydrophobic interactions between the alkyl chains assisted by strong
      electrostatic attractions between the headgroups and hydrogen bonds between the
      spacers lead to the formation of less surface active premicellar aggregates in
      bulk solution, resulting in the increase of CMC. If these interactions are
      weakened or inhibited, less surface active premicellar aggregates are no longer
      formed in the mixtures, and thus the CMC values are reduced. The work reveals
      that the combination of two surfactants with great self-assembling ability
      separately may have strong intermolecular binding interactions; however, their
      mixtures do not always generate superior synergism properties. Only moderate
      intermolecular interaction can generate the strongest synergism in CMC reduction.

PMID- 24933419
TI  - Survival of Salmonella spp. and fecal indicator bacteria in Vietnamese biogas
      digesters receiving pig slurry.
AB  - Small-scale biogas digesters are widely promoted worldwide as a sustainable
      technology to manage livestock manure. In Vietnam, pig slurry is commonly applied
      to biogas digesters for production of gas for electricity and cooking with the
      effluent being used to fertilize field crops, vegetables and fish ponds. Slurry
      may contain a variety of zoonotic pathogens, e.g. Salmonella spp., which are able
      to cause disease in humans either through direct contact with slurry or by fecal
      contamination of water and foods. The objective of this study was to evaluate the
      survival of Salmonella spp. and the fecal indicator bacteria, enterococci, E.
      coli, and spores of Clostridium perfringens in biogas digesters operated by small
      scale Vietnamese pig farmers. The serovar and antimicrobial susceptibility of the
      Salmonella spp. isolated were also established. The study was conducted in 12
      farms (6 farms with and 6 farms without toilet connected) located in Hanam
      province, Vietnam. Sampling of pig slurry and biogas effluent was done during two
      seasons. Results showed that the concentration of enterococci, E. coli, and
      Clostridium perfringens spores was overall reduced by only 1-2 log10-units in the
      biogas digesters when comparing raw slurry and biogas effluent. Salmonella spp.
      was found in both raw slurry and biogas effluent. A total of 19 Salmonella
      serovars were identified, with the main serovars being Salmonella Typhimurium
      (55/138), Salmonella enterica serovar 4,[5],12:i:- (19/138), Salmonella
      Weltevreden (9/138) and Salmonella Rissen (9/138). The Salmonella serovars showed
      similar antimicrobial resistance patterns to those previously reported from
      Vietnam. When promoting biogas, farmers should be made aware that effluent should
      only be used as fertilizer for crops not consumed raw and that indiscriminate
      discharge of effluent are likely to contaminate water recipients, e.g. drinking
      water sources, with pathogens. Relevant authorities should promote safe animal
      manure management practices to farmers and regulations be updated to ensure food
      safety and public health.

PMID- 24933420
TI  - Exploring the role of 2-chloro-6-fluoro substitution in 2-alkylthio-6-benzyl-5
      alkylpyrimidin-4(3H)-ones: effects in HIV-1-infected cells and in HIV-1 reverse
      transcriptase enzymes.
AB  - A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2
      (alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6
      difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1
      reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs
      showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV
      1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl)
      substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with
      the highest, wide-spectrum inhibitory activity against HIV-1. Three
      representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic
      centers were resolved into their individual stereoisomers and showed a
      significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest
      antiviral activity well correlating with the R absolute configuration to the
      stereogenic center of the C6-benzylic position in both cellular and enzymatic
      tests. Application of previously reported COMBINEr protocol on 9c and 10c
      confirmed the influence of the stereogenic centers on their binding modes in the
      HIV-1 RT.

PMID- 24933422
TI  - Oncostatin M overexpression induces matrix deposition, STAT3 activation, and
      SMAD1 Dysregulation in lungs of fibrosis-resistant BALB/c mice.
AB  - Adverse health outcomes in pulmonary fibrosis are associated with extracellular
      matrix (ECM) accumulation. Although transforming growth factor-beta (TGF-beta)
      has been reported to be an important regulator of fibrosis pathogenesis, TGF-beta
      independent pathways may also be involved. Here, we investigated responses of
      putative relatively fibrosis-resistant BALB/c mice to transient pulmonary
      overexpression of oncostatin M (OSM) using an adenovirus vector encoding OSM
      (AdOSM) and compared responses with the relatively fibrosis-prone C57Bl/6 strain.
      Interestingly, BALB/c mice showed similar ECM accumulation and collagen 1A1 and
      3A1 mRNA elevation to C57Bl/6 mice 7 days after endotracheal administration of
      AdOSM. TGF-beta1 mRNA levels and pSMAD2 signal were not regulated in either
      strain in total lung extracts. In contrast to C57Bl/6 mice, BALB/c mice lacked
      eosinophil, Th2 cytokine, and pro-inflammatory cytokine elevation in the
      broncholveolar space. OSM overexpression induced STAT3 activation and SMAD1/5/8
      signaling suppression in lung from both mice strains, which was associated with a
      downregulation of BMPR2 and BMP ligands, and increased expression of the BMP
      antagonist gremlin. Although we also observed STAT3 activation and SMAD1/5/8
      signaling suppression in mouse lung fibroblast cultures in vitro upon OSM
      stimulation, immunohistochemistry analyses indicated that the AdOSM-induced
      pSMAD1/5/8 signal suppression was primarily localized to the airway epithelium.
      Other gp130 cytokines including IL-6, LIF, CT-1, but not IL-31, also induced
      STAT3 activation and SMAD1/5/8 signaling suppression in C10 mouse lung epithelial
      cells and BEAS 2B bronchial epithelial cells, and we found that pharmacological
      inhibition of STAT3 activation reversed OSM-induced SMAD1/5/8 signaling
      suppression in vitro. The results demonstrate that OSM induces ECM accumulation
      in fibrosis-resistant BALB/c mouse lung in the absence of Th2 inflammation or TGF
      beta signaling, and highlight a dichotomy of STAT3 activation versus SMAD1
      suppression in this process. 

PMID- 24933421
TI  - 17beta-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I
      dependent Grp78 induction in osteoblasts.
AB  - Although many studies have suggested that estrogen prevents postmenopausal bone
      loss partially due to its anti-apoptosis effects in osteoblasts, the underlying
      mechanism has not been fully elucidated. In the present study, we found that
      17beta-estradiol (17beta-E2), one of the primary estrogens, inhibited endoplasmic
      reticulum (ER) stress-induced apoptosis in MC3T3-E1 cells and primary
      osteoblasts. Interestingly, 17beta-E2-promoted Grp78 induction, but not CHOP
      induction in response to ER stress. We further confirmed that Grp78-specific
      siRNA reversed the inhibition of 17beta-E2 on ER stress-induced apoptosis by
      activating caspase-12 and caspase-3. Moreover, we found that 17beta-E2 markedly
      increased the phosphorylated TFII-I levels and nuclear localization of TFII-I in
      ER stress conditions. 17beta-E2 stimulated Grp78 promoter activity in a dose
      dependent manner in the presence of TFII-I and enhanced the binding of TFII-I to
      the Grp78 promoter. In addition, 17beta-E2 notably increased phosphorylated
      ERK1/2 levels and Ras kinase activity in MC3T3-E1 cells. The ERK1/2 activity
      specific inhibitor U0126 remarkably blocked 17beta-E2-induced TFII-I
      phosphorylation and Grp78 expression in response to ER stress. Together, 17beta
      E2 protected MC3T3-E1 cells against ER stress-induced apoptosis by promoting Ras
      ERK1/2-TFII-I signaling pathway-dependent Grp78 induction.

PMID- 24933423
TI  - Adenoviral targeting using genetically incorporated camelid single variable
      domains.
AB  - The unique ability of human adenovirus serotype 5 (Ad5) to accomplish efficient
      transduction has allowed the use of Ad5-based vectors for a range of gene therapy
      applications. Several strategies have been developed to alter tropism of Ad
      vectors to achieve a cell-specific gene delivery by using fiber modifications via
      genetic incorporation of targeting motifs. In this study, we have explored the
      utility of novel anti-human carcinoembryonic antigen (hCEA) single variable
      domains derived from heavy chain (VHH) camelid family of antibodies to achieve
      targeted gene transfer. To obtain anti-CEA VHHs, we produced a VHH-display
      library from peripheral blood lymphocytes RNA of alpacas at the peak of immune
      response to the hCEA antigen (Ag). We genetically incorporated an anti-hCEA VHH
      into a de-knobbed Ad5 fiber-fibritin chimera and demonstrated selective targeting
      to the cognate epitope expressed on the membrane surface of target cells. We
      report that the anti-hCEA VHH used in this study retains Ag recognition
      functionality and provides specificity for gene transfer of capsid-modified Ad5
      vectors. These studies clearly demonstrated the feasibility of retargeting of Ad5
      based gene transfer using VHHs. 

PMID- 24933426
TI  - OVERWEIGHT/OBESITY AND HUMAN CAPITAL FORMATION FROM INFANCY TO ADOLESCENCE:
      EVIDENCE FROM TWO LARGE US COHORTS.
AB  - Body mass index (BMI) levels in US children and adolescents have increased over
      the past several decades. The negative health effects of this trend are well
      documented. Recent work has evaluated the potential effects on skills formation.
      Studies are mixed on whether there is an association between high BMI and skills
      outcomes, and those that estimate causal effects find none. This paper offers
      estimates on the causal effect of BMI-defined overweight and obesity on skills
      formation using two large cohorts of contemporary US children followed from
      infancy to 5 years and from kindergarten (6 years) to the eighth grade (14
      years). Significant negative associations were observed in the random effects
      models for males in early life with respect to a mental skills assessment, for
      females during the pre-school years for reading and maths assessments, for both
      males and females during the schooling years for reading assessments and for
      females during the schooling years for maths assessments. Fixed effects models
      yielded a significant negative association only with respect to the latter. The
      implication of these findings is that any improvement in skills outcomes that may
      accompany reductions in obesity prevalence may depend on whether interventions
      are general to overall health productivity or whether they are specific to
      dietary and exercise behaviours. 

PMID- 24933424
TI  - The tissue is the issue: improved methylome analysis from paraffin-embedded
      tissues by application of the HOPE technique.
AB  - Alterations in the DNA methylome are characteristic for numerous diseases and a
      typical hallmark of cancer. Therefore, DNA methylation is currently under
      investigation in research labs and has also entered diagnostics. Recently,
      protocols like the BeadChip technology have become commercially available to
      study DNA methylation in an array format and semiquantitative fashion. However,
      it is known that fixation of the sample material with formalin prior to BeadChip
      analysis can affect the results. In this study we compared the influence of
      fixation on the outcome of BeadChip analysis. From six patients each a lung
      cancer tissue sample and a corresponding tumor-free lung tissue sample were
      collected. The samples were separated into three pieces. One piece of each sample
      was fixed with formalin, another one by the non-cross-linking HOPE technique
      (Hepes-glutamic acid buffer mediated Organic solvent Protection Effect).
      Subsequently, both became paraffin embedded. As a reference, the remaining third
      piece was cryopreserved. In addition we used three adenocarcinoma cell lines
      (H838, A549, and H1650) to validate the results from patient tissues. We show
      that using the HOPE technique instead of formalin largely prevents the
      introduction of formalin-fixation related artifacts. An ANOVA analysis
      significantly separated HOPE- and cryopreserved from formalin-fixed samples
      (FDR<0.05), while differences in the methylation data obtained from HOPE-fixed
      and cryopreserved material were minor. Consequently, HOPE fixation is superior to
      formalin fixation if a subsequent BeadChip analysis of paraffin-embedded sample
      material is intended. 

PMID- 24933427
TI  - beta-cyclodextrin and curcumin, a potent cocktail for disaggregating and/or
      inhibiting amyloids: a case study with alpha-synuclein.
AB  - Aggregation of alpha-synuclein has been implicated in Parkinson's disease (PD).
      While many compounds are known to inhibit alpha-synuclein aggregation,
      dissolution of aggregates into their constituent monomers cannot be readily
      achieved. In this study, using a range of techniques, we have shown that an
      optimized cocktail of curcumin and beta-cyclodextrin, at appreciably low
      concentrations, not only inhibited aggregation but also broke up the preformed
      aggregates almost completely. We propose that these compounds exhibit synergy in
      their action and thus provide us with the exciting prospect of working toward the
      development of a suitable drug candidate for prevention and treatment of PD. 

PMID- 24933425
TI  - Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like
      inflammatory response.
AB  - Preeclampsia is a human pregnancy-specific disorder characterized by a placental
      pro-inflammatory response in combination with an imbalance of angiogenic factors
      and clinical symptoms, including hypertension and proteinuria. Insufficient
      uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion
      during placentation is believed to be responsible for many of the molecular
      events leading to the clinical manifestations of this disease. We investigated
      the use of hypoxic treatment of the dual placental perfusion system as a model
      for preeclampsia. A modified perfusion technique allowed us to achieve a mean
      soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia
      and <3% for hypoxia (as a model for preeclampsia). We assayed for the levels of
      different inflammatory cytokines, oxidative stress markers, as well as other
      factors, such as endothelin (ET)-1 that are known to be implicated as part of the
      inflammatory response in preeclampsia. Our results show a significant increase
      under hypoxia in the levels of different inflammatory cytokines, including IL-6
      (P=0.002), IL-8 (P<0.0001), TNF-alpha (P=0.032) and IFN-gamma (P=0.009) at 360
      min in maternal venous samples (n=6). There was also a significant increase in ET
      1 levels under hypoxia both on the maternal side at 30 min (P=0.003) and fetal
      side at 360 min (P=0.036) (n=6). Other markers of oxidative stress, including
      malondialdehyde and 8-iso-protaglandin F2alpha (P=0.009) also show increased
      levels. Overall, these findings indicate that exposure of ex vivo dually perfused
      placental tissue to hypoxia provides a useful model for mimicking the
      inflammatory response characteristic of preeclampsia. This would therefore
      provide a powerful tool for studying and further delineating the molecular
      mechanisms involved in the underlying pathophysiology of preeclampsia. 

PMID- 24933428
TI  - Antioxidants and human diseases.
AB  - Oxidative stress plays a pivotal role in the development of human diseases.
      Reactive oxygen species (ROS) that includes hydrogen peroxide, hyphochlorus acid,
      superoxide anion, singlet oxygen, lipid peroxides, hypochlorite and hydroxyl
      radical are involved in growth, differentiation, progression and death of the
      cell. They can react with membrane lipids, nucleic acids, proteins, enzymes and
      other small molecules. Low concentrations of ROS has an indispensable role in
      intracellular signalling and defence against pathogens, while, higher amounts of
      ROS play a role in number of human diseases, including arthritis, cancer,
      diabetes, atherosclerosis, ischemia, failures in immunity and endocrine
      functions. Antioxidants presumably act as safeguard against the accumulation of
      ROS and their elimination from the system. The aim of this review is to highlight
      advances in understanding of the ROS and also to summarize the detailed impact
      and involvement of antioxidants in selected human diseases. 

PMID- 24933429
TI  - A framework for unpacking cognitive benefits of distributed complex visual
      displays.
AB  - What are the advantages and disadvantages of spatially stacked (i.e., when
      information sources are presented side-by-side) versus distributed (i.e., when
      information sources are sitting on top of one another with only the top source
      fully visible) organizations of information? We introduce a new theoretical
      decomposition of these advantages and disadvantages (information internalization,
      information access, and information externalization costs), along with a new
      analytic technique for measuring each theoretical aspects using eye tracking.
      Thirty-eight scientists-in-training solved a complex data interpretation problem
      using either a distributed or a stacked display. Display format influenced all 3
      factors, but in opposing ways: stacked displays increase internalization and
      externalization costs but decrease information access costs. The framework
      reveals trade-offs among the 3 factors that can be precisely characterized to
      guide interface user design and optimization.

PMID- 24933430
TI  - Carbohydrate ingestion before and during soccer match play and blood glucose and
      lactate concentrations.
AB  - CONTEXT: The ingestion of carbohydrate (CHO) before and during exercise and at
      halftime is commonly recommended to soccer players for maintaining blood glucose
      concentrations throughout match play. However, an exercise-induced rebound
      glycemic response has been observed in the early stages of the second half of
      simulated soccer-specific exercise when CHO-electrolyte beverages were consumed
      regularly. Therefore, the metabolic effects of CHO beverage consumption
      throughout soccer match play remain unclear. OBJECTIVE: To investigate the blood
      glucose and blood lactate responses to CHOs ingested before and during soccer
      match play. DESIGN: Crossover study. SETTING: Applied research study. PATIENTS OR
      OTHER PARTICIPANTS: Ten male outfield academy soccer players (age = 15.6 +/- 0.2
      years, height = 1.74 +/- 0.02 m, mass = 65.3 +/- 1.9 kg, estimated maximal oxygen
      consumption = 58.4 +/- 0.8 mL.kg(-1).min(-1)). INTERVENTION(S): Players received
      a 6% CHO-electrolyte solution or an electrolyte (placebo) solution 2 hours before
      kickoff, before each half (within 10 minutes), and every 15 minutes throughout
      exercise. Blood samples were obtained at rest, every 15 minutes during the match
      (first half: 0-15, 15-30, and 30-45 minutes; second half: 45-60, 60-75, and 75-90
      minutes) and 10 minutes into the halftime break. MAIN OUTCOME MEASURE(S):
      Metabolic responses (blood glucose and blood lactate concentrations) and markers
      of exercise intensity (heart rate) were recorded. RESULTS: Supplementation
      influenced the blood glucose response to exercise (time * treatment interaction
      effect: P <= .05), such that glucose concentrations were higher at 30 to 45
      minutes in the CHO than in the placebo condition. However, in the second half,
      blood glucose concentrations were similar between conditions because of transient
      reductions from peak values occurring in both trials at halftime. Blood lactate
      concentrations were elevated above those at rest in the first 15 minutes of
      exercise (time-of-sample effect: P < .001) and remained elevated throughout
      exercise. Supplementation did not influence the pattern of response (time *
      treatment interaction effect: P = .49). CONCLUSIONS: Ingestion of a 6% CHO
      electrolyte beverage before and during soccer match play did not benefit blood
      glucose concentrations throughout the second half of exercise.

PMID- 24933431
TI  - Reliability and validity evidence of multiple balance assessments in athletes
      with a concussion.
AB  - CONTEXT: An estimated 300 000 sport-related concussion injuries occur in the
      United States annually. Approximately 30% of individuals with concussions
      experience balance disturbances. Common methods of balance assessment include the
      Clinical Test of Sensory Organization and Balance (CTSIB), the Sensory
      Organization Test (SOT), the Balance Error Scoring System (BESS), and the Romberg
      test; however, the National Collegiate Athletic Association recommended the Wii
      Fit as an alternative measure of balance in athletes with a concussion. A central
      concern regarding the implementation of the Wii Fit is whether it is reliable and
      valid for measuring balance disturbance in athletes with concussion. OBJECTIVE:
      To examine the reliability and validity evidence for the CTSIB, SOT, BESS,
      Romberg test, and Wii Fit for detecting balance disturbance in athletes with a
      concussion. DATA SOURCES: Literature considered for review included publications
      with reliability and validity data for the assessments of balance (CTSIB, SOT,
      BESS, Romberg test, and Wii Fit) from PubMed, PsycINFO, and CINAHL. DATA
      EXTRACTION: We identified 63 relevant articles for consideration in the review.
      Of the 63 articles, 28 were considered appropriate for inclusion and 35 were
      excluded. DATA SYNTHESIS: No current reliability or validity information supports
      the use of the CTSIB, SOT, Romberg test, or Wii Fit for balance assessment in
      athletes with a concussion. The BESS demonstrated moderate to high reliability
      (interclass correlation coefficient = 0.87) and low to moderate validity
      (sensitivity = 34%, specificity = 87%). However, the Romberg test and Wii Fit
      have been shown to be reliable tools in the assessment of balance in Parkinson
      patients. CONCLUSIONS: The BESS can evaluate balance problems after a concussion.
      However, it lacks the ability to detect balance problems after the third day of
      recovery. Further investigation is needed to establish the use of the CTSIB, SOT,
      Romberg test, and Wii Fit for assessing balance in athletes with concussions.

PMID- 24933432
TI  - Cohort study design: an underutilized approach for advancement of evidence-based
      and patient-centered practice in athletic training.
AB  - OBJECTIVE: Providing patient-centered care requires consideration of numerous
      factors when making decisions that will influence a patient's health status.
      BACKGROUND: Clinical decisions should be informed by relevant research evidence,
      but the literature often lacks pertinent information for problems encountered in
      routine clinical practice. Although a randomized clinical trial provides the best
      research design to ensure the internal validity of study findings, ethical
      considerations and the competitive culture of sport often preclude random
      assignment of patients or participants to a control condition. CLINICAL
      ADVANTAGES: A cohort study design and Bayesian approach to data analysis can
      provide valuable evidence to support clinical decisions. Dichotomous
      classification of both an outcome and 1 or more predictive factors permits
      quantification of the likelihood of occurrence of a specified outcome.
      CONCLUSIONS: Multifactorial prediction models can reduce uncertainty in clinical
      decision making and facilitate the individualization of treatment, thereby
      supporting delivery of clinical services that are both evidence based and patient
      centered.

PMID- 24933433
TI  - The secondary school football coach's relationship with the athletic trainer and
      perspectives on exertional heat stroke.
AB  - CONTEXT: Prior researchers have examined the first-aid knowledge and decision
      making among high school coaches, but little is known about their perceived
      knowledge of exertional heat stroke (EHS) or their relationships with an athletic
      trainer (AT). OBJECTIVE: To examine secondary school football coaches' perceived
      knowledge of EHS and their professional relationship with an AT. DESIGN:
      Qualitative study. SETTING: Web-based management system. PATIENTS OR OTHER
      PARTICIPANTS: Thirty-eight secondary school head football coaches (37 men, 1
      woman) participated in this study. Their average age was 47 +/- 10 years old, and
      they had 12 +/- 9 years' experience as a head football coach. DATA COLLECTION AND
      ANALYSIS: Participants responded to a series of online questions that were
      focused on their perceived knowledge of EHS and professional relationships with
      ATs. Data credibility was established through multiple-analyst triangulation and
      peer review. We analyzed the data by borrowing from the principles of a general
      inductive approach. RESULTS: Two dominant themes emerged from the data: perceived
      self-confidence of the secondary school coach and the influence of the AT. The
      first theme highlighted the perceived confidence, due to basic emergency care
      training, of the coach regarding management of an emergency situation, despite a
      lack of knowledge. The second theme illustrated the secondary school coach's
      positive professional relationships with ATs regarding patient care and emergency
      procedures. Of the coaches who participated, 89% (34 out of 38) indicated
      positive interactions with their ATs. CONCLUSIONS: These secondary school coaches
      were unaware of the potential causes of EHS or the symptoms associated with EHS,
      and they had higher perceived levels of self-confidence in management abilities
      than indicated by their perceived knowledge level. The secondary school football
      coaches valued and understood the role of the AT regarding patient and emergency
      care.

PMID- 24933434
TI  - Microglia and their CX3CR1 signaling are involved in hippocampal- but not
      olfactory bulb-related memory and neurogenesis.
AB  - Recent studies demonstrate that microglia play an important role in cognitive and
      neuroplasticity processes, at least partly via microglial CX3C receptor 1
      (CX3CR1) signaling. Furthermore, microglia are responsive to environmental
      enrichment (EE), which modulates learning, memory and neurogenesis. In the
      present study we examined the role of microglial CX3CR1 signaling in hippocampal-
      and olfactory-bulb (OB)-related memory and neurogenesis in homozygous mice with
      microglia-specific transgenic expression of GFP under the CX3CR1 promoter
      (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as
      heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient
      mice displayed better hippocampal-dependent memory functioning and olfactory
      recognition, along with increased number and soma size of hippocampal microglia,
      suggestive of mild activation status, but no changes in OB microglia. A similar
      increase in hippocampal-dependent memory functioning and microglia number was
      also induced by pharmacological inhibition of CX3CR1 signaling, using chronic
      (2weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE
      improved hippocampal-dependent memory and neurogenesis, and increased hippocampal
      microglia number and soma size, whereas odor enrichment (OE) improved olfactory
      recognition and OB neurogenesis without changing OB microglia status. In CX3CR1
      deficient mice, EE and OE did not produce any further improvement in memory
      functioning or neurogenesis and had no effect on microglial status. These results
      support the notion that in the hippocampus microglia and their interactions with
      neurons via the CX3CR1 play an important role in memory functioning and
      neurogenesis, whereas in the OB microglia do not seem to be involved in these
      processes. 

PMID- 24933435
TI  - Impact of extreme climate and bioinvasion on temporal coupling of spring herring
      (Clupea harengus m.) larvae and their prey.
AB  - We used weekly observational data from mid-May to end of July in 1958-2012 in
      Gulf of Riga to investigate temporal coupling between spring herring larvae and
      their first prey - copepod nauplii, under the extreme hydroclimatic conditions.
      We focused on a small shallow estuary that is important nursery ground for larvae
      of the Gulf of Riga (Baltic Sea) herring population. We quantified the effect of
      extreme values of the winter air temperatures, time of ice retreat and spring
      water temperatures on the timing of peak abundance of herring larvae and copepod
      nauplii. We also assessed whether the invasion of the non-native cladoceran
      Cercopagis pengoi had notable effect on timing and abundance of copepod nauplii
      during the peak occurrence of herring larvae. In the years of earliest ice
      retreat the peak abundance of herring larvae was five weeks earlier than in the
      years of latest ice retreat, while the timing of nauplii remained unchanged.
      Abundant presence of the C. pengoi affected neither timing nor maximum abundance
      of copepod nauplii during the herring larvae first feeding period. Thus, we
      conclude that processes induced by climate variability are superior to invasion
      of C. pengoi in determining the timing and coupling of larval herring and copepod
      nauplii.

PMID- 24933436
TI  - Population structure and spread of the polychaete Diopatra biscayensis along the
      French Atlantic coast: human-assisted transport by-passes larval dispersal.
AB  - Intertidal populations of the ecosystem engineering polychaete, Diopatra
      biscayensis, were analyzed on the French Atlantic coast for three years with
      individual size estimated from tube-cap aperture. All but the northernmost
      population along the Bay of Biscay have yearly recruitment. Individuals live 3-5
      years and are likely reproductive as one year olds. Simulations indicate
      dispersal distances are <50 km; yet, populations also exist within the Normano
      Breton Gulf in the western English Channel, more than 450 km from the
      northernmost Bay of Biscay population at La Trinite-sur-Mer. Three of the four
      populations in the Normano-Breton Gulf have no young of the year, but are near to
      active mussel culture where mussel seed is transported on ropes from dense D.
      biscayensis areas in the Vendee-Charente region in the Bay of Biscay. The
      majority of D. biscayensis were adjacent to the likely source, mussel seed ropes.
      Transport assisted by aquaculture is the likely explanation for the populations
      in the Normano-Breton Gulf. 

PMID- 24933437
TI  - Grazing rate of zebra mussel in a shallow eutrophicated bay of the Baltic Sea.
AB  - Benthic suspension feeding is an important process in coastal ecosystems. Among
      all the World's oceans, coastal ecosystems are the most modified by human impact
      and changing at accelerating pace. It is complicated to understand, how various
      environmental factors affect feeding rates of suspension feeders in their natural
      habitats. Thus, shapes of such relationships are poorly described for several
      intersections of environmental gradients. In this study, relationships between
      grazing rates of an invasive bivalve Dreissena polymorpha and ambient
      environmental factors were investigated in a turbid eutrophic bay of the central
      Baltic Sea using a novel modelling method of Boosted Regression Trees (BRT), a
      statistical tool able to handle non-normal distributions, complex relationships,
      and interactive effects. Feeding rates of mussels were derived from field
      populations by measuring the content of algal pigments in specimens collected
      from their natural habitat. The content of pigments was converted to feeding rate
      separately each time using field experiments measuring simultaneously the content
      of pigments and biodeposition of mussels. The results suggest that feeding rates
      of D. polymorpha are related to several environmental factors which gradients
      outreach the optimal range for the local mussel population. All the observed
      effects were non-linear with complex shapes. Variability along the resource
      gradient was the most important predictor of mussel feeding, followed by salinity
      and disturbance caused by wind. The most important interaction occurred between
      disturbance and resource gradient, while feeding function showed more plasticity
      along the latter. Mapping of environmental tipping points with the aid of machine
      learning methods may enable to concentrate the most relevant information about
      ecological functions worldwide.

PMID- 24933438
TI  - Realized niche width of a brackish water submerged aquatic vegetation under
      current environmental conditions and projected influences of climate change.
AB  - Little is known about how organisms might respond to multiple climate stressors
      and this lack of knowledge limits our ability to manage coastal ecosystems under
      contemporary climate change. Ecological models provide managers and decision
      makers with greater certainty that the systems affected by their decisions are
      accurately represented. In this study Boosted Regression Trees modelling was used
      to relate the cover of submerged aquatic vegetation to the abiotic environment in
      the brackish Baltic Sea. The analyses showed that the majority of the studied
      submerged aquatic species are most sensitive to changes in water temperature,
      current velocity and winter ice scour. Surprisingly, water salinity, turbidity
      and eutrophication have little impact on the distributional pattern of the
      studied biota. Both small and large scale environmental variability contributes
      to the variability of submerged aquatic vegetation. When modelling species
      distribution under the projected influences of climate change, all of the studied
      submerged aquatic species appear to be very resilient to a broad range of
      environmental perturbation and biomass gains are expected when seawater
      temperature increases. This is mainly because vegetation develops faster in
      spring and has a longer growing season under the projected climate change
      scenario.

PMID- 24933440
TI  - Medial migration of lag screw after gamma nailing.
AB  - Fractures of the proximal femur are common in the elderly population.
      Intramedullary nailing has become the standard treatment for intertrochanteric
      fractures although several extramedullary implants (e.g. dynamic hip screw (DHS),
      blade plate, locking compression plate (LCP), etc.) exist. However, despite this
      being a very common operation in traumatology, there are numerous associated
      complications. We report the rare complication of the migration of the medial lag
      screw into the pelvis at five and a half weeks postoperatively. The implant was
      removed and replaced by a total hip arthroplasty with simultaneous grafting of
      the acetabular defect and strapping of the greater trochanter. The evolution was
      favourable. We also present a review of the literature and analyze our case. 

PMID- 24933442
TI  - Surgical excision of ununited hook of hamate fractures via the carpal tunnel
      approach.
AB  - INTRODUCTION: Direct excision of a symptomatic ununited hook of hamate fracture
      is the gold standard, most frequently via a Guyon space approach. The open carpal
      tunnel approach is another option, which has not previously been commonly
      considered and not reported in a peer review journal. Our study aims to highlight
      the carpal tunnel approach as a successful technique in a consecutive series of
      ununited hook of hamate fractures. PATIENTS AND METHODS: Seven patients (all male
      and mean age 30.7 years) were reviewed with symptomatic ununited fractures
      following a period of cast immobilization. All the patients operated on underwent
      excision of the hook of hamate fragment via the open carpal tunnel approach.
      RESULTS: All patients successfully returned to their pre-injury level of
      functioning after 8-12 weeks and there were no complications. CONCLUSIONS: Our
      study highlights the open carpal tunnel approach as a successful technique for
      open excision of symptomatic ununited hook of hamate fractures, because of its
      familiarity, ease of performance, excellent visualization and low morbidity.
      Level of Evidence IV Case Series.

PMID- 24933439
TI  - Eph receptor tyrosine kinases in cancer stem cells.
AB  - Eph receptor tyrosine kinases (RTKs) and their ligands, ephrins, play critical
      roles in development, tissue homeostasis, and cancer. Because Eph receptors are
      expressed in most adult stem cell niches and in many types of cancers, it has
      been long suspected that this family of RTKs may also regulate the function of
      cancer stem-like cells (CSCs). This review will focus on recent studies to
      elucidate the contribution of Eph/ephrin molecules in CSC self-renewal and
      tumorigenicity, as well as describe efforts to target these molecules in cancer.
      Because CSCs are often resistant to therapeutic intervention and have been shown
      to depend on Eph RTKs for self-renewal, targeting Eph receptors may hold promise
      for the treatment of drug-resistant cancers. 

PMID- 24933441
TI  - A description of the severity of equestrian-related injuries (ERIs) using
      clinical parameters and patient-reported outcomes.
AB  - INTRODUCTION: Despite a number of injury prevention campaigns and interventions,
      horse riding continues to be a dangerous activity, resulting in more accidents
      per hour than motorcycling, skiing and football. Injuries are often serious, with
      one in four patients requiring admission to hospital. This study aims to describe
      the severity of equestrian-related injuries (ERIs) using both clinical parameters
      and patient-reported outcomes. PATIENTS AND METHODS: A retrospective study of all
      patients aged >=18 years admitted to The Alfred Hospital between January 2003 and
      January 2008 with an ERI was performed. Specific clinical data were extracted
      from the medical record. In addition, a questionnaire was conducted identifying
      the details of the accident, the required recovery time and levels of ongoing
      pain and physical disability. RESULTS: During the study period 172 patients met
      the inclusion criteria. There were three deaths (2%). Eighty-two patients (48%)
      suffered head injuries. Forty-one patients (24%) were admitted to the ICU and 31
      patients (18%) required mechanical ventilation. On discharge, 41 patients (24%)
      required transfer to a sub-acute rehabilitation facility. One-hundred-and-twenty
      four patients (72%) completed the questionnaire. Thirty-nine respondents (31%)
      were not wearing a helmet. Among patients injured for more than 6 months, 38
      (35%) still experienced moderate or severe pain or disability. Ninety-five
      patients had returned to work at the time of review, among which 47(50%) required
      longer than 6 months to recover, and 40 (42%) returned at a reduced capacity.
      CONCLUSIONS: The clinical and patient-reported outcomes of ERIs requiring
      hospital admission are poor. Persistent pain and disability are common, even up
      to 5 years post-injury. A large proportion of patients required longer than 6
      months to return to work and many return at a reduced capacity.

PMID- 24933443
TI  - Cranial injuries secondary to assault with a machete.
AB  - BACKGROUND: Assaults with a machete cause compound skull fractures which present
      as a neurosurgical emergency. We aimed to profile cranial injuries caused by a
      machete over a 10 year period in a single neurosurgical unit. MATERIALS AND
      METHODS: Retrospective data analysis of cranial injuries following assault with a
      machete, admitted to the neurosurgery ward, from January 2003 to December 2012
      was performed. Medical records were analyzed for demographics, clinical
      presentation, CT scan findings, surgical treatment and Glasgow Outcome Scale
      (GOS) at discharge. Management involved wound debridement with antibiotic cover.
      RESULTS: Of 185 patients treated 172 (93%) were male. Mean age was 31+/-11.4
      years. Mean GCS on admission was 13+/-2. Presenting features were focal
      neurological deficit (48%), brain matter oozing from wounds (20%), and post
      traumatic seizures (12%). Depressed skull fractures were found in 162 (88%)
      patients. Findings on CT brain scan were intra-cranial haematoma (88%),
      pneumocephalus (39%) and features of raised intra-cranial pressure (37%). Thirty
      one patients (17%) presented with septic head wounds. One hundred and fifty seven
      patients (85%) were treated surgically. The median hospital stay was 8 days
      (range 1-145). The median GOS at discharge was 5 (range 1-5). Twelve patients
      died within the same admission (6.5%). CONCLUSION: Machetes cause complex cranial
      injuries with associated neurological deficit and should be treated as
      neurosurgical emergency. Timeous intervention and good surgical principles are
      advocated to prevent secondary infection and further neurological deterioration.

PMID- 24933444
TI  - Engineering Escherichia coli for light-activated cytolysis of mammalian cells.
AB  - By delivering payloads in response to specific exogenous stimuli, smart bacterial
      therapeutics have the potential to overcome many limitations of conventional
      therapies, including poor targeting specificity and dosage control in current
      cancer treatments. Although not yet explored as a trigger for bacterial drug
      delivery, light is an ideal induction mechanism because it offers fine
      spatiotemporal control and is easily and safely administered. Using recent
      advances in optogenetics, we have engineered two strains of Escherichia coli to
      secrete a potent mammalian cytotoxin in response to blue or red light. The tools
      in this study demonstrate the initial feasibility of light-activated bacterial
      therapeutics for applications such as tumor cytolysis, and their modular nature
      should enable simple substitution of other payloads of interest. 

PMID- 24933445
TI  - Pathogenicity and treatment of Bartonella infections.
AB  - Bartonella spp. are responsible for emerging and re-emerging diseases around the
      world. The majority of human infections are caused by Bartonella henselae,
      Bartonella quintana and Bartonella bacilliformis, although other Bartonella spp.
      have also been associated with clinical manifestations in humans. The severity of
      Bartonella infection correlates with the patient's immune status. Clinical
      manifestations can range from benign and self-limited to severe and life
      threatening disease. Clinical conditions associated with Bartonella spp. include
      local lymphadenopathy, bacteraemia, endocarditis, and tissue colonisation
      resulting in bacillary angiomatosis and peliosis hepatis. Without treatment,
      Bartonella infection can cause high mortality. To date, no single treatment is
      effective for all Bartonella-associated diseases. In the absence of systematic
      reviews, treatment decisions for Bartonella infections are based on case reports
      that test a limited number of patients. Antibiotics do not significantly affect
      the cure rate in patients with Bartonella lymphadenopathy. Patients with
      Bartonella spp. bacteraemia should be treated with gentamicin and doxycycline,
      but chloramphenicol has been proposed for the treatment of B. bacilliformis
      bacteraemia. Gentamicin in combination with doxycycline is considered the best
      treatment regimen for endocarditis, and erythromycin is the first-line antibiotic
      therapy for the treatment of angioproliferative lesions. Rifampicin or
      streptomycin can be used to treat verruga peruana. In this review, we present
      recent data and recommendations related to the treatment of Bartonella infections
      based on the pathogenicity of Bartonella spp. 

PMID- 24933447
TI  - Outpatient parenteral antimicrobial therapy (OPAT) for infectious endocarditis in
      Spain.

PMID- 24933446
TI  - Photodynamic antibacterial and antibiofilm activity of RLP068/Cl against
      Staphylococcus aureus and Pseudomonas aeruginosa forming biofilms on prosthetic
      material.
AB  - Prosthetic joint infections (PJIs) are becoming a growing public health concern
      in developed countries as more people undergo arthroplasty for bone fixation or
      joint replacement. Because a wide range of bacterial strains responsible for PJIs
      can produce biofilms on prosthetic implants and because the biofilm structure
      confers elevated bacterial resistance to antibiotic therapy, new drugs and
      therapies are needed to improve the clinical outcome of treatment of PJIs.
      Antimicrobial photodynamic therapy (APDT), a non-antibiotic broad-spectrum
      antimicrobial treatment, is also active against multidrug-resistant micro
      organisms such as meticillin-resistant Staphylococcus aureus (MRSA) and
      Pseudomonas aeruginosa. APDT uses a photosensitiser that targets bacterial cells
      following exposure to visible light. APDT with RLP068/Cl, a novel
      photosensitiser, was studied by confocal laser scanning microscopy (CLSM) to
      evaluate the disruption of MRSA and P. aeruginosa biofilms on prosthetic
      material. Quantitative CLSM studies showed a reduction in biofilm biomass
      (biofilm disruption) and a decrease in viable cell numbers, as determined by
      standard plate counting, in the S. aureus and P. aeruginosa biofilms exposed to
      APDT with the photosensitiser RLP068/Cl. APDT with RLP068/Cl may be a useful
      approach to the treatment of PJI-associated biofilms. 

PMID- 24933448
TI  - Clinical utility of caspofungin eye drops in fungal keratitis.
AB  - Treatment of fungal keratitis remains challenging. To date, only the polyenes and
      azoles are commonly used topically in the management of fungal keratitis.
      Natamycin, a polyene, is the only antifungal eye drop that is commercially
      available; the remainder are prepared in-house and are used in an 'off-label'
      manner. Failure of medical treatment for fungal keratitis is common, hence there
      is a need for more effective topical antifungal therapy. To increase the
      antifungal eye drop armamentarium, it is important to investigate the utility of
      other classes of antifungal agents for topical use. Caspofungin, an echinocandin
      antifungal agent, could potentially be used to address the existing shortcomings.
      However, little is known about the usefulness of topically administered
      caspofungin. This review will briefly explore the incidence, epidemiology and
      antifungal treatment of fungal keratitis. It will focus primarily on evidence
      related to the efficacy, safety and practicality of using caspofungin eye drops
      in fungal keratitis. 

PMID- 24933449
TI  - Global health imaging curriculum in radiology residency programs: the
      fundamentals.
AB  - Recent advances in imaging technology have created new opportunities for medical
      imaging to improve health care in resource-restricted countries around the world.
      Radiology residents are increasingly interested in global health and imaging
      outreach, yet infrastructure and opportunities for international outreach are
      limited. With the recent change in the ABR exam schedule, residents now have more
      flexibility in the fourth year of training to pursue elective interests,
      including participation in global health projects. Creating a formalized global
      health imaging curriculum will improve the quality, quantity, and overall impact
      of initiatives undertaken by residents and their training programs. A curriculum
      is proposed that provides content, opportunities for global health project
      development, and established metrics for effective evaluation and assessment.
      Four components considered integral to a global health imaging curriculum are
      described: (1) global and public health education; (2) targeted travel medicine
      education; (3) basic imaging proficiency; and (4) practice attitudes and
      accountability. Methods are presented of differentiating curricula to increase
      applicability across the spectrum of training programs that vary in available
      resources. A blueprint is presented for formalizing a global health curriculum or
      elective rotation within a program, as well as a resource for residents,
      radiologists, and organizations to make a meaningful impact on global health. 

PMID- 24933450
TI  - ACR Appropriateness Criteria Headache.
AB  - Most patients presenting with uncomplicated, nontraumatic, primary headache do
      not require imaging. When history, physical, or neurologic examination elicits
      "red flags" or critical features of the headache, then further investigation with
      imaging may be warranted to exclude a secondary cause. Imaging procedures may be
      diagnostically useful for patients with headaches that are: associated with
      trauma; new, worse, or abrupt onset; thunderclap; radiating to the neck; due to
      trigeminal autonomic cephalgia; persistent and positional; and temporal in older
      individuals. Pregnant patients, immunocompromised individuals, cancer patients,
      and patients with papilledema or systemic illnesses, including hypercoagulable
      disorders may benefit from imaging. Unlike most headaches, those associated with
      cough, exertion, or sexual activity usually require neuroimaging with MRI of the
      brain with and without contrast to exclude potentially underlying pathology
      before a primary headache syndrome is diagnosed. The ACR Appropriateness Criteria
      are evidence-based guidelines for specific clinical conditions that are reviewed
      every 2 years by a multidisciplinary expert panel. The guideline development and
      review include an extensive analysis of current medical literature from peer
      reviewed journals and the application of a well-established consensus methodology
      (modified Delphi) to rate the appropriateness of imaging and treatment procedures
      by the panel. In those instances in which evidence is lacking or not definitive,
      expert opinion may be used to recommend imaging or treatment. 

PMID- 24933451
TI  - Effectiveness and cost-effectiveness of individually tailored Internet-delivered
      cognitive behavior therapy for anxiety disorders in a primary care population: a
      randomized controlled trial.
AB  - A significant proportion of the general population suffers from anxiety
      disorders, often with comorbid psychiatric conditions. Internet-delivered
      cognitive behavior therapy (ICBT) has been found to be a potent treatment for
      patients with specific psychiatric conditions. The aim of this trial was to
      investigate the effectiveness and cost-effectiveness of ICBT when tailoring the
      treatment to address comorbidities and preferences for primary-care patients with
      a principal anxiety disorder. One hundred participants were recruited through
      their primary-care contact and randomized to either treatment or an active
      control group. The treatment consisted of 7-10 weekly individually assigned
      modules guided by online therapists. At post-treatment, 46% of the treatment
      group had achieved clinically significant improvement on the primary outcome
      measure (CORE-OM) and between-group effect sizes ranged from d = 0.20 to 0.86,
      with a mean effect of d = 0.59. At one-year follow-up, within-group effect sizes
      varied between d = 0.53 to 1.00. Cost analysis showed significant reduction of
      total costs for the ICBT group, the results were maintained at one-year follow-up
      and the incremental cost-effectiveness ratio favored ICBT compared to control
      group. Individually tailored ICBT is an effective and cost-effective treatment
      for primary-care patients with anxiety disorders with or without comorbidities.
      TRIAL REGISTRATION: Clinicaltrials.gov: NCT01390168.

PMID- 24933452
TI  - Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma:
      treatment outcomes of a prospective, multicentric clinical study.
AB  - BACKGROUND AND PURPOSE: To evaluate long-term outcome in locoregionally advanced
      nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy
      (IMRT) and concurrent chemotherapy. MATERIAL AND METHODS: Between January 2006
      and August 2008, 249 patients with stage III-IVb NPC were treated by IMRT plus
      concurrent chemotherapy in this multicenter prospective study. RESULTS: With a
      mean follow-up of 54.1 months, the 5-year actuarial rates of overall survival
      (OS), local recurrence-free survival (LRFS), regional recurrence-free survival
      (RRFS), and distant metastasis-free survival (DMFS) were 78.4%, 86.8%, 88.4%,
      78.0%, respectively. There were 29 local recurrences, 25 regional recurrences and
      52 distant metastases, respectively. Distant metastasis is the main cause of
      treatment failure. N-stage was an independent prognostic factor for LRFS, RRFS,
      DMFS and OS. Acute toxicity ?grade III mainly consisted of mucositis (34.9%),
      neutropenia (11.2%), xerostomia (5.6%), and dermatitis (5.2%). The main
      documented late toxicity was xerostomia, and the severity of xerostomia decreased
      over time. At 24 months after treatment, 13.2% of patients had grade 2
      xerostomia, and none had grade 3 or 4 xerostomia. CONCLUSIONS: IMRT with
      concurrent cisplatin chemotherapy resulted in encouraging rates of local and
      distant control and overall survival with acceptable rates of acute and limited
      rates of late toxicity in patients with locoregionally advanced NPC. Distant
      metastasis remained the main cause of failure. More effective systemic therapy
      should be explored for patients with advanced N-stage.

PMID- 24933453
TI  - Comparison and validation of some ITS primer pairs useful for fungal
      metabarcoding studies.
AB  - Current metabarcoding studies aiming to characterize microbial communities
      generally rely on the amplification and sequencing of relatively short DNA
      regions. For fungi, the internal transcribed spacer (ITS) region in the ribosomal
      RNA (rRNA) operon has been accepted as the formal fungal barcode. Despite an
      increasing number of fungal metabarcoding studies, the amplification efficiency
      of primers is generally not tested prior to their application in metabarcoding
      studies. Some of the challenges that metabarcoding primers should overcome
      efficiently are the amplification of target DNA strands in samples rich in non
      target DNA and environmental pollutants, such as humic acids, that may have been
      co-extracted with DNA. In the current study, three selected primer pairs were
      tested for their suitability as fungal metabarcoding primers. The selected primer
      pairs include two primer pairs that have been frequently used in fungal
      metabarcoding studies (ITS1F/ITS2 and ITS3/ITS4) and a primer pair (ITS86F/ITS4)
      that has been shown to efficiently amplify the ITS2 region of a broad range of
      fungal taxa in environmental soil samples. The selected primer pairs were
      evaluated in a 454 amplicon pyrosequencing experiment, real-time PCR (qPCR)
      experiments and in silico analyses. Results indicate that experimental evaluation
      of primers provides valuable information that could aid in the selection of
      suitable primers for fungal metabarcoding studies. Furthermore, we show that the
      ITS86F/ITS4 primer pair outperforms other primer pairs tested in terms of in
      silico primer efficiency, PCR efficiency, coverage, number of reads and number of
      species-level operational taxonomic units (OTUs) obtained. These traits push the
      ITS86F/ITS4 primer pair forward as highly suitable for studying fungal diversity
      and community structures using DNA metabarcoding. 

PMID- 24933454
TI  - MicroRNA-196a/-196b promote cell metastasis via negative regulation of radixin in
      human gastric cancer.
AB  - MicroRNAs (miRNAs) play an important role to contribute carcinogenesis. The aim
      of the current study was to identify useful biomarkers from miRNAs. Differential
      miRNA profiles were analyzed using the miRNA qRT-PCR-based assay. Two of the most
      upregulated miRNAs were selected and validated. The miR-196a/-196b levels were
      significantly increased in gastric cancer (GC) tissues (n=109). Overexpression of
      miR-196a/-196b was significantly associated with tumor progression and poorer 5
      year survival outcomes. Overexpression of miR-196a/-196b enhances GC cell
      migration and invasion. Further, radixin was identified as a target gene of miR
      196a/-196b. Elevated miR-196a/-196b expression in GC cells led to reduced radixin
      protein levels and vice versa. Notably, an inverse correlation between miR-196a/
      196b and radixin mRNA and protein expression was observed in GC tissues with in
      situ hybridization and immunohistochemistry analyses. Together, miR-196a/-196b
      inhibitory oligonucleotides or overexpression of the radixin may thus have
      therapeutic potential in suppressing GC metastasis. 

PMID- 24933455
TI  - Liver transplantation with grafts from donors who die from suicide by hanging: a
      matched cohort study.
AB  - INTRODUCTION: Hanging is a common method of suicide globally, and the incidence
      is increasing at an alarming rate. The purpose of this study was to analyze our
      experience with the use of liver grafts from donors whose cause of death is
      suicidal hanging and to evaluate the outcome of the graft recipients. PATIENTS
      AND METHODS: Twenty-four consecutive patients were transplanted with grafts
      obtained from suicidal hanging donors. These patients (group A) were case-matched
      to 24 patients who underwent liver transplantation with a liver graft from a
      brain-dead donor whose cause of death was not hanging or strangulation (group B).
      The analysis was focused on postoperative complications, graft, and recipient
      outcomes. RESULTS: Donors in group A showed a significantly higher mean [+/-2
      standard deviation] serum aspartate aminotransferase and alanine aminotransferase
      compared to group B (aspartate aminotransferase, 168[166] vs. 57[67] IU/L;
      P=0.006; alanine aminotransferase, 151[197] vs. 58[103] IU/L; P=0.049); however,
      there was no difference in graft failure rates between the two groups [8.3% (n=2)
      in each group]. Overall 30-day postoperative morbidity, 1-year and 5-year
      survivals were comparable in both groups (P=0.96, P=0.35, P=0.69, respectively).
      CONCLUSION: The use of grafts from suicidal hanging donors (without hemodynamic
      instability and with downward trend in the donor transaminases) is not associated
      with higher post-liver transplantation complication rates and does not negatively
      influence recipient's outcome.

PMID- 24933456
TI  - Development of antidonor antibody directed toward non-major histocompatibility
      complex antigens in tolerant animals.
AB  - BACKGROUND: The clinical significance of antibodies directed against antigens
      other than major histocompatibility complex (MHC) antigens is poorly understood,
      and there are few large animal models in which such antibodies can be examined.
      We studied, both retrospectively and prospectively, the development of antibodies
      to non-MHC antigens in tolerant miniature swine. METHODS: Our database was
      assessed for cases of antidonor antibody formation in tolerant animals over the
      last 20 years. Flow cytometry, absorption assays, and familial analyses for
      inheritance pattern of the gene(s) potentially responsible for the antibody
      reactivities were carried out, and an animal determined to be negative for this
      reactivity was immunized by a skin graft and subcutaneous injections of
      peripheral blood monocyte cells from an antigen-positive donor. RESULTS: Sixteen
      of 469 tolerant animals tested were found to have developed antidonor antibodies.
      These antibodies were found to be specific for the same, presumably single, non
      MHC antigen. Familial analyses indicated that the gene encoding this antigen was
      expressed in an autosomal-dominant manner in approximately 95% of the herd. In a
      prospective study, antidonor antibodies with the same specificity as those
      observed retrospectively were successfully induced in an antigen-negative animal
      after immunization with peripheral blood monocyte cells. CONCLUSION: To our
      knowledge, this is the first report of the development of antibodies to a highly
      prevalent, non-MHC antigen present on peripheral blood mononuclear cells and
      developing in tolerant animals without signs of graft dysfunction. Considering
      the concern often raised by the appearance of antidonor antibodies in transplant
      recipients, these data could have important implications for clinical
      transplantation.

PMID- 24933457
TI  - Atypical hemolytic uremic syndrome recurrence after kidney transplantation.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a
      high recurrence rate after kidney transplantation. In most cases, aHUS are caused
      by genetic mutations of components of the complement alternative pathway. In this
      single-center series, we present our data of 12 consecutive patients with aHUS
      and the outcome after kidney transplantation. METHODS: In this 10-year
      retrospective study, we identified 12 patients with aHUS who were managed in our
      center since 2003. We reviewed clinical data, including genetic testing,
      posttransplant course and response to therapy including the prophylactic use of
      eculizumab. RESULTS: Overall, eight patients are women. Six of our patients have
      at least one genetic mutation causing aHUS, including 4 with complement factor H
      mutations. Nine patients had at least one previous kidney transplant that failed
      secondary to recurrent aHUS (75% of our patients). Three patients were treated
      with eculizumab and plasmapheresis for recurrent aHUS after kidney
      transplantation; two of them responded to the therapy. Four patients received
      prophylactic eculizumab; three of them received 6 months and one has been on life
      long therapy. No signs of recurrence have been observed in these 4 patients so
      far. CONCLUSION: Genetic mutations of the complement alternative pathway were
      confirmed in half of our patients, most of those mutations are in CHF. We
      demonstrate that treatment or prophylaxis with eculizumab was effective in
      reversing or preventing aHUS whether or not genetic complement mutations were
      identified.

PMID- 24933458
TI  - Regulatory T-cell therapy in the induction of transplant tolerance: the issue of
      subpopulations.
AB  - Clinical tolerance induction to permit minimization or cessation of
      immunosuppressive drugs is one of the key research goals in solid organ
      transplantation. The use of ex vivo expanded or manipulated immunologic cells,
      including CD4CD25FOXP3 regulatory T cells (Tregs), to achieve this aim is already
      a reality, with several trials currently recruiting patients. Tregs are a highly
      suppressive, nonredundant, population of regulatory cells that prevent the
      development of autoimmune diseases in mammals. Data from transplanted humans and
      animal models support the notion that Tregs can mediate both induction and
      adoptive transfer of transplantation tolerance. However, human Tregs are highly
      heterogeneous and include subpopulations with the potential to produce the
      proinflammatory cytokine interleukin-17, which has been linked to transplant
      rejection. Tregs are also small in number in the peripheral circulation, thus
      they require ex vivo expansion before infusion into man. Selection of the most
      appropriate Treg population for cell therapy is, therefore, a critical step in
      ensuring successful clinical outcomes. In this review, we discuss Treg
      subpopulations, their subdivision based on nonmutually exclusive criteria of
      origin, expression of immunologic markers and function, availability in the
      peripheral blood of patients awaiting transplantation, and their suitability for
      programs of cell-based therapy. 

PMID- 24933459
TI  - Antibodies to denatured human leukocyte antigen: relevant or just noise?

PMID- 24933460
TI  - U-CN versus Ce-NC coordination in trivalent complexes derived from M[N(SiMe3)2]3
      (M = Ce, U).
AB  - Reactions of [MN*3] (M = Ce, U; N* = N(SiMe3)2) and NR4CN (R = Me, Et, or (n)Bu)
      or KCN in the presence of 18-crown-6 afforded the series of cyanido-bridged
      dinuclear compounds [NEt4][(MN*3)2(MU-CN)] (M = Ce, 2a, and U, 2b), [K(18-crown
      6)(THF)2][(CeN*3)2(MU-CN)] (2'a), and [K(18-crown-6)][(UN*3)2(MU-CN)] (2'b), and
      the mononuclear mono-, bis-, and tris(cyanide) complexes [NEt4][MN*3(CN)] (M =
      Ce, 1a(Et), and U, 1b(Et)), [NMe4][MN*3(CN)] (M = Ce, 1a(Me), and U, 1b(Me)),
      [K(18-crown-6)][MN*3(CN)] (M = Ce, 1'a, and U, 1'b), [N(n)Bu4]2[MN*3(CN)2] (M =
      Ce, 3a, and U, 3b), [K(18-crown-6)]2[MN*3(CN)2] (M = Ce, 3'a, and U, 3'b), and
      [N(n)Bu4]2[MN*2(CN)3] (M = Ce, 4a, and U, 4b). The mono- and bis(cyanide)
      complexes were found to be in equilibrium. The formation constant of 3'b (K3'b)
      from 1'b at 10  degrees C in THF is equal to 5(1) * 10(-3), and -DeltaH3'b =
      104(2) kJ mol(-1) and -DeltaS3'b = 330(5) J mol(-1) K(-1). The bis(cyanide)
      compound 3a or 3b was slowly transformed in solution into an equimolar mixture of
      the mono- and tris(cyanide) derivatives with elimination of N(n)Bu4N*. The
      crystal structures of 1a(Me), 1b(Me), 1'a.toluene, 1'b.toluene, 2'a, 2'b, 3a,
      3'a, 3'b, 3'a.2benzene, 3'b.2benzene, 4a.0.5THF, and 4b.Et2O were determined.
      Crystals of the bis(cyanide) uranium complexes 3'b and 3'b.2benzene are
      isomorphous with those of the cerium counterparts 3'a and 3'a.2benzene, but they
      are not isostructural since the data revealed distinct coordination modes of the
      CN group, through the C or N atom to the U or Ce metal center, respectively. This
      differentiation has been analyzed using density functional theory calculations.
      The observed preferential coordination of the cyanide and isocyanide ions toward
      uranium or cerium in the bis(cyanide) complexes is corroborated by the
      consideration of the binding energies of these groups to the metals and by the
      comparison of DFT optimized geometries with the crystal structures. The better
      affinity of the cyanide ligand toward U(III) over Ce(III) metal center is related
      to the better energy matching between the 6d/5f uranium orbitals and the cyanide
      ligand ones, leading to a non-negligible covalent character of the bonding. 

PMID- 24933462
TI  - Genome analysis of non-human primate polyomaviruses.
AB  - Polyomaviruses have so far only been isolated from mammals and birds. Typical for
      all members of this family is their double-stranded genome of approximately 5000
      base-pairs which can be divided into an early region encoding at least two
      functional proteins, the large and small tumor antigens, and a late region
      encompassing genes for the capsid proteins VP1 and VP2. During the last 10 years
      several novel polyomaviruses have been described in non-human primates and man.
      This review compares the non-human primate polyomavirus genomes that have been
      completely sequenced with each other and with the genomes of human
      polyomaviruses. We predict the presence of protein- and microRNA-encoding
      sequences. Our analyses demonstrate that several genetically distinct groups of
      non-human primate polyomaviruses exist, that different polyomaviruses can infect
      the same non-human primate species but that most of their proteins display highly
      similar domains and motifs, indicating conservation of key functions.

PMID- 24933461
TI  - Ecophysiology of Anopheles gambiae s.l.: persistence in the Sahel.
AB  - The dry-season biology of malaria vectors is poorly understood, especially in
      arid environments when no surface waters are available for several months, such
      as during the dry season in the Sahel. Here we reappraise results on the dry
      season physiology of members of the Anopheles gambiae s.l. complex in the broad
      context of dormancy in insects and especially in mosquitoes. We examine evidence
      on seasonal changes in reproduction, metabolism, stress tolerance, nutrition,
      molecular regulation, and environmental conditions and determine if the current
      results are compatible with dry-season diapause (aestivation) as the primary
      strategy for persistence throughout the dry season in the Sahel. In the process,
      we point out critical gaps in our knowledge that future studies can fill. We find
      compelling evidence that members of the An. gambiae s.l. complex undergo a form
      of aestivation during the Sahelian dry season by shifting energetic resources
      away from reproduction and towards increased longevity. Considering the
      differences between winter at temperate latitudes, which entails immobility of
      the insect and hence reliance on physiological solutions, as opposed to the
      Sahelian dry season, which restricts reproduction exclusively, we propose that
      behavioral changes play an important role in complementing physiological changes
      in this strategy. 

PMID- 24933463
TI  - Interaction between infectious diseases and personality traits: ACP1*C as a
      potential mediator.
AB  - In geographical regions characterized by high pathogen prevalence, it has been
      shown that human populations tend to be characterized by lower levels of
      extraversion (E) and openness to experience (OtE). According to the "behavioral
      immune system" hypothesis, the reduction of extraversion and openness levels
      represents a behavioral defense against infections. Like the 'classical' immune
      system, the "behavioral immune system" could also be shaped by its underlying
      genetic background. Previous studies have shown that the *C allele of the ACP1
      gene confers increased susceptibility to infectious/parasitic diseases. We
      hypothesized that carriers of the ACP1*C allele should likewise be associated
      with reduced E and OtE. We tested this hypothesis using two samples comprised of
      153 students from Southern California (Group 1), and 162 female subjects
      recruited from an executive health program (Group 2), genotyped for ACP1
      polymorphism and evaluated by the NEO Five-Factor Inventory (NEO-FFI). ACP1 was
      significantly associated with E: we found that carriers of ACP1*C showed reduced
      scores for E (Group 1: beta=-4.263, P=0.027; Group 2: beta=-8.315, P=0.003; Group
      1+Group 2: beta=-5.366, P=0.001). Across groups, ACP1 was only marginally
      associated with OtE. In conclusion, the present study found that the ACP1*C
      allele, previously associated with an increased vulnerability to
      infectious/parasitic diseases may also be able to shape behavioral immune
      defenses by interaction with the level of E. 

PMID- 24933464
TI  - Bioactivity and phytochemical characterization of Arenaria montana L.
AB  - The bioactivity (antioxidant and cytotoxic activities) of the aqueous and
      methanolic extracts of Arenaria montana L., a plant commonly used in Portuguese
      folk medicine, was evaluated and compared. Furthermore, the phytochemical
      composition was determined based on hydrophilic (sugars, organic acids and
      phenolic compounds) and lipophilic (fatty acids and tocopherols) compounds, in
      order to valorize this plant material as a functional food/nutraceutical.
      Fructose, oxalic acid, methyl-luteolin 2''-O-feruloylhexosyl-C-hexoside, alpha
      tocopherol, and linoleic acid were the main individual compounds found in A.
      montana. In general, the aqueous extract showed higher antioxidant and cytotoxic
      activities than the methanolic extract; the latter showed activity only against
      HeLa and HepG2 cell lines. Both aqueous and methanolic extracts showed some
      hepatotoxicity but at higher doses than the ones active for tumor cell lines.
      Moreover, the aqueous extract of A. montana may be used as a functional food or
      nutraceutical due to the high antioxidant and cytotoxic activities, and due to
      the presence of bioactive compounds. As far as we know, this is the first report
      on the phytochemical composition and bioactivity of A. montana. 

PMID- 24933465
TI  - Formation of newly synthesized adeno-associated virus capsids in the cell
      nucleus.
AB  - Adeno-associated virus (AAV) particles inside the nucleus of a HEK 293 cell are
      shown by electron microscopy. Cells have been triple-transfected for vector
      production and were analyzed for capsid formation three days later. Newly
      assembled particle are visible as seemingly unstructured conglomerates or crystal
      like arrays.

PMID- 24933467
TI  - Control and eventual eradication of Trypanosoma evansi infection in dromedary
      camels after an episodic outbreak in mainland Spain: an example in a non-endemic
      area.
AB  - In 2008, Trypanosoma evansi was detected on a camel farm in mainland Spain. The
      animals were isolated, confined in a closed stable, and treated twice with
      melarsamine (Cymelarsan((r)), Merial, Lyon, France) with an interval of 1 month.
      Clinical and laboratory examinations by means of parasitological, serological,
      and molecular procedures (polymerase chain reaction (PCR)) were carried out
      regularly for 6 years. After the treatment, all parasitemic camels were cleared
      of parasites, and in the seropositive camels a progressive decrease in antibody
      levels was observed, with complete disappearance of antibodies between 15 and 21
      months, except in one animal which showed doubtful Ag-Ab reaction at 21 months
      post treatment. In the next assessment, 6 months later, the diagnostic tests
      conducted on all animals had a negative result. The diagnostic and therapeutic
      tools recently developed against T. evansi will evidence new and alternative
      approaches after the parasite is detected, particularly if outbreak occurs in
      geographically localized areas in territories free of the disease. 

PMID- 24933468
TI  - Descriptive findings from analysis of a large database of cattle worm egg count
      and larval culture results collected across Australia between 2002 and 2012.
AB  - Results from worm egg counts (WECs) of cattle from across Australia over an 11
      year period have been analysed to provide contemporary data on WEC and worm genus
      distribution in Australian cattle. A sampling kit consisted of ten sample
      containers. Faecal samples were collected into each sampling kit from groups of
      cattle and WEC and larval cultures were conducted using standard procedures. A
      submission form was completed for each kit with data requested including date of
      sampling, property address, age, average estimated weight and production type of
      cattle, last drench used and date of drenching. Regional analysis was done by
      postcode region and postcode regions were grouped into bioclimatic regions. A
      total of 5069 submissions were received from 2002 to the end of 2012 representing
      over 50,000 individual faecal samples. Seventy-seven percent of cattle sampled
      were no more than 2 years of age with the remainder representing a range of age
      groups. Samples were collected from all of the significant cattle producing
      regions of Australia. There was a tendency for higher geometric mean WEC in
      cattle in northern Australia and in high rainfall areas along the east coast of
      Australia. Geometric mean WEC for bioclimatic regions varied seasonally with a
      peak in autumn in regions with summer dominant rainfall, but little seasonal
      variation in regions with winter dominant rainfall patterns. Worm genera cultured
      varied throughout Australia with Cooperia spp. being most prevalent across the
      country, followed by Haemonchus spp. and Oesophagostomum spp. in summer rainfall
      dominant regions and Ostertagia spp. and Trichostrongylus spp. in winter rainfall
      regions. In the coastal, tablelands, and temperate rangelands regions of NSW,
      Haemonchus spp. were as prevalent as Cooperia spp. during autumn months and
      levels of Haemonchus spp. found in south-western Western Australia were higher
      than previously documented. These data provide an up-to-date summary of internal
      parasites in Australian cattle. Regional differences in WEC between northern and
      southern Australia are evident and should be further explored. These data suggest
      that there has been a move to Cooperia spp. being the predominant worm genus in
      Australian cattle, with increasing levels of Haemonchus spp. being evident in
      southern temperate regions of Australia. 

PMID- 24933469
TI  - Polypyrrole-coated electrospun poly(lactic acid) fibrous scaffold: effects of
      coating on electrical conductivity and neural cell growth.
AB  - Neuronal activities play critical roles in both neurogenesis and neural
      regeneration. In that sense, electrically conductive and biocompatible
      biomaterial scaffolds can be applied in various applications of neural tissue
      engineering. In this study, we fabricated a novel biomaterial for neural tissue
      engineering applications by coating electrospun poly(lactic acid) (PLA)
      nanofibers with a conducting polymer, polypyrole (PPy), via admicellar
      polymerization. Optimal conditions for polymerization and preparation of PPy
      coated electrospun PLA nanofibers were obtained by comparing results from
      scanning electron microscopy, X-ray photoelectron spectrometer, and surface
      conductivity tests. In vitro cell culture experiments showed that PPy-coated
      electrospun PLA fibrous scaffold is not toxic. The scaffold could support
      attachment and migration of neural progenitor cells. Neurons derived from
      progenitor exhibited long neurite outgrowth under electrical stimulation. Our
      study concluded that PPy-coated electrospun PLA fibers had a good
      biocompatibility with neural progenitor cells and may serve as a promising
      material for controlling progenitor cell behaviors and enhancing neural repair. 

PMID- 24933471
TI  - Pressure-Dependent Properties of Elementary Hydrophobic Interactions:
      Ramifications for Activation Properties of Protein Folding.
AB  - Hydration effects on a pair of methane molecules are investigated by extensive
      constant-pressure (NPT) sampling using the TIP4P model of water under 1, 1000,
      2000, and 3000 atm. The volume distributions of pure water and of methanes plus
      water are determined directly as functions of methane-methane distance xi. The
      corresponding excess isothermal and adiabatic compressibilities are estimated
      from the pressure-dependent methane excess volume. The dependence of excess
      volume on xi is oscillatory for small xi. The maxima of excess volume and
      compressibility are seen near the desolvation barrier (db) of the potential of
      mean force (PMF). These features may be understood by the development, near the
      db, of a void volume encased by a molecular (Connolly) surface defined using a
      water-sized probe. These db properties for two methanes are consistent with well
      corroborated experimental observations of positive activation volumes for protein
      folding and some experiments suggesting a slightly higher compressibility for the
      folding transition state than the unfolded state. At high pressures, the volumes
      at the PMF solvent-separated minimum and the contact-minimum configurations are
      both smaller than the volume at large xi. This trend provides a rationalization
      for the compactness of pressure-denatured states of proteins. Taking the packing
      densities of pure nonpolar phases into consideration, our simulation results
      suggest that whether the activation volume of unfolding is positive or negative
      hinges on the packing compactness of the protein core. Volume change can be but
      is not necessarily monotonic along the folding pathway.

PMID- 24933472
TI  - Moonlighting adenosine deaminase: a target protein for drug development.
AB  - Interest in adenosine deaminase (ADA) in the context of medicine has mainly
      focused on its enzymatic activity. This is justified by the importance of the
      reaction catalyzed by ADA not only for the intracellular purine metabolism, but
      also for the extracellular purine metabolism as well, because of its capacity as
      a regulator of the concentration of extracellular adenosine that is able to
      activate adenosine receptors (ARs). In recent years, other important roles have
      been described for ADA. One of these, with special relevance in immunology, is
      the capacity of ADA to act as a costimulator, promoting T-cell proliferation and
      differentiation mainly by interacting with the differentiation cluster CD26.
      Another role is the ability of ADA to act as an allosteric modulator of ARs.
      These receptors have very general physiological implications, particularly in the
      neurological system where they play an important role. Thus, ADA, being a single
      chain protein, performs more than one function, consistent with the definition of
      a moonlighting protein. Although ADA has never been associated with moonlighting
      proteins, here we consider ADA as an example of this family of multifunctional
      proteins. In this review, we discuss the different roles of ADA and their
      pathological implications. We propose a mechanism by which some of their
      moonlighting functions can be coordinated. We also suggest that drugs modulating
      ADA properties may act as modulators of the moonlighting functions of ADA, giving
      them additional potential medical interest. 

PMID- 24933473
TI  - Flexible organic light-emitting diodes with enhanced light out-coupling
      efficiency fabricated on a double-sided nanotextured substrate.
AB  - High-efficiency organic light-emitting diodes (OLEDs) have generated tremendous
      research interest. One of the exciting possibilities of OLEDs is the use of
      flexible plastic substrates, which unfortunately have a mismatching refractive
      index compared with the conventional ITO anode and the air. To unlock the light
      loss on flexible plastic, we report a high-efficiency flexible OLED directly
      fabricated on a double-sided nanotextured polycarbonate substrate by thermal
      nanoimprint lithography. The template for the nanoimprint process is a replicate
      from a silica arrayed with nanopillars and fabricated by ICP etching through a
      SiO2 colloidal spheres mask. It has been shown that with the internal quasi
      periodical scattering gratings the efficiency enhancement can reach 50% for a
      green light OLED, and with an external antireflection structure, the normal
      transmittance is increased from 89% to 94% for paraboloid-like pillars. The OLED
      directly fabricated on the double-sided nanotextured polycarbonate substrate has
      reached an enhancing factor of ~2.8 for the current efficiency. 

PMID- 24933470
TI  - Transcription activator-like effectors: a toolkit for synthetic biology.
AB  - Transcription activator-like effectors (TALEs) are proteins secreted by
      Xanthomonas bacteria to aid the infection of plant species. TALEs assist
      infections by binding to specific DNA sequences and activating the expression of
      host genes. Recent results show that TALE proteins consist of a central repeat
      domain, which determines the DNA targeting specificity and can be rapidly
      synthesized de novo. Considering the highly modular nature of TALEs, their
      versatility, and the ease of constructing these proteins, this technology can
      have important implications for synthetic biology applications. Here, we review
      developments in the area with a particular focus on modifications for custom and
      controllable gene regulation. 

PMID- 24933474
TI  - A new growth curve model for biological growth: some inferential studies on the
      growth of Cirrhinus mrigala.
AB  - Growth of living organisms is a fundamental biological process. It depicts the
      physiological development of the species related to the environment. Mathematical
      development of growth curve models has a long history since its birth. We propose
      a mathematical model to describe the evolution of relative growth rate as a
      function of time based on a real life experiment on a major Indian Carp Cirrhinus
      mrigala. We establish that the proposed model is able to describe the fish growth
      dynamics more accurately for our experimental data than some existing models e.g.
      logistic, Gompertz, exponential. Approximate expressions of the points of
      inflection and the time of achieving the maximum relative growth rate are
      derived. We study, in detail, the existence of a nonlinear least squares
      estimator of the model parameters and their consistency properties. Test
      statistics is developed to study the equality of points of inflection and
      equality of the amount of time necessary to achieve the maximum relative growth
      rate for a species at two different locations. Using the theory of variance
      stabilizing transformations, we propose a new test statistic to test the effect
      of the decay parameter for the proposed growth law. The testing procedure is
      found to be more sensitive in comparison with the test based on nonlinear least
      squares estimates. Our proposed model provides a general framework to model
      growth in other disciplines as well. 

PMID- 24933475
TI  - Quantifying the effects of anagenetic and cladogenetic evolution.
AB  - An ongoing debate in evolutionary biology is whether phenotypic change occurs
      predominantly around the time of speciation or whether it instead accumulates
      gradually over time. In this work I propose a general framework incorporating
      both types of change, quantify the effects of speciational change via the
      correlation between species and attribute the proportion of change to each type.
      I discuss results of parameter estimation of Hominoid body size in this light. I
      derive mathematical formulae related to this problem, the probability generating
      functions of the number of speciation events along a randomly drawn lineage and
      from the most recent common ancestor of two randomly chosen tip species for a
      conditioned Yule tree. Additionally I obtain in closed form the variance of the
      distance from the root to the most recent common ancestor of two randomly chosen
      tip species. 

PMID- 24933476
TI  - Retention of a 24-hour time memory in Syrian hamsters carrying the 20-hour short
      circadian period mutation in casein kinase-1epsilon (ck1epsilontau/tau).
AB  - Circadian rhythmic expression of conditioned place avoidance (CPA) was produced
      in Syrian hamsters homozygous for the circadian short period mutation, tau. In
      constant dim red light neither the 20 h endogenous period, nor a 20 h place
      conditioning schedule eliminated the 24 h modulation of CPA behavior described
      previously for wild type (wt) hamsters and other species. Tau mutants exhibited a
      20 h rhythm superimposed on the 24 h modulation. The 20 h component was removed
      selectively with lesions of the suprachiasmatic nucleus. Wt animals conditioned
      on a 20 h schedule did not produce a 20 h rhythm, but still expressed the 24 h
      modulation. The results show that the context entrainable oscillator (CEO)
      underlying memory for the timing of an unconditioned stimulus, retains a period
      of about 24 h regardless of clock gene background (tau mutation) and/or the
      conditioning schedule (24 vs 20 h). Therefore the CEO responsible for time memory
      is distinct from the biological clock controlling activity; the underlying
      circadian molecular mechanisms may differ from the ubiquitous transcription
      translation feedback oscillator; and time memory itself is not classically
      conditioned.

PMID- 24933477
TI  - Propane dehydrogenation over Pt-Cu bimetallic catalysts: the nature of coke
      deposition and the role of copper.
AB  - This paper describes an investigation of the promotional effect of Cu on the
      catalytic performance of Pt/Al2O3 catalysts for propane dehydrogenation. We have
      shown that Pt/Al2O3 catalysts possess higher propylene selectivity and lower
      deactivation rate as well as enhanced anti-coking ability upon Cu addition. The
      optimized loading content of Cu is 0.5 wt%, which increases the propylene
      selectivity to 90.8% with a propylene yield of 36.5%. The origin of the enhanced
      catalytic performance and anti-coking ability of the Pt-Cu/Al2O3 catalyst is
      ascribed to the intimate interaction between Pt and Cu, which is confirmed by the
      change of particle morphology and atomic electronic environment of the catalyst.
      The Pt-Cu interaction inhibits propylene adsorption and elevates the energy
      barrier of C-C bond rupture. The inhibited propylene adsorption diminishes the
      possibility of coke formation and suppresses the cracking reaction towards the
      formation of lighter hydrocarbons on Pt-Cu/Al2O3, while a higher energy barrier
      for C-C bond cleavage suppresses the methane formation. 

PMID- 24933478
TI  - Pineal tumours: Experience of the French National Register and the Lyon School,
      results and considerations.
AB  - The experience of the French National Register of pineal tumours and the
      experience of the Lyon School are reported. Data were collected from 26 French
      neurosurgical centres from 1989 in Lyons and in other centres from 1997. For
      radiological and pathological studies, 517 cases were considered while only 452
      with sufficient clinical and follow-up data were retained for further analysis.
      These data highlight the importance of the initial diagnosis for a therapeutic
      strategy that can be completely different in cases of pineal or germ cell
      tumours. As regards the latter, chemotherapy and radiotherapy can avoid surgery.
      Pineocytomas are benign lesions and their complete removal guarantees the cure.
      Pineal parenchymal tumours with intermediate differentiation (PTT-ID) require
      complete removal and complementary treatment in cases of histological
      abnormalities with approximately 66% of patients who remain alive. Pineoblastomas
      have a poor prognosis and the rate of survival in the French National Register is
      only 33% of cases. Germinomas can be treated with chemotherapy or radiotherapy
      alone and generally the indication for surgical removal is limited to residual
      tumours. The rate of survival is 64% at 10 years. For papillary tumours of the
      pineal region (PTPR) complete removal is a good prognostic factor. Radiotherapy
      seems to be effective in cases of residual tumours. The experience and results
      with radiosurgery treatment have been limited in the French national and Lyon
      experience. 

PMID- 24933479
TI  - Preferences regarding disclosure of a diagnosis of dementia: a systematic review.
AB  - BACKGROUND: Studies in memory clinics suggest that the majority of patients would
      like to know of a diagnosis of dementia. It is less clear what preferences are in
      the community. Our objective was to review the literature on preferences
      regarding disclosure of a diagnosis of dementia and to assess key arguments in
      favor of and against disclosure. METHODS: Systematic search of empirical studies
      was performed in Pubmed, Embase, and Psycinfo. We extracted preferences of
      individuals without cognitive impairment (general population; relatives of
      dementia patients; and physicians) and preferences of individuals referred to a
      memory clinic or already diagnosed with dementia. A meta-analysis was done using
      a random effects model. Our main conclusions are based on studies with a response
      rate >=75%. RESULTS: We included 23 articles (9.065 respondents). In studies with
      individuals without cognitive impairment, the pooled percentage in favor of
      disclosure was 90.7% (95%CI: 83.8%-97.5%). In studies with patients who were
      referred to a memory clinic or already diagnosed with dementia, the pooled
      percentage that considered disclosure favorable was 84.8% (95%CI: 75.6%-94.0%).
      The central arguments in favor of disclosure pertained to autonomy and the
      possibility to plan one's future. Arguments against disclosure were fear of
      getting upset and that knowing has no use. CONCLUSIONS: The vast majority of
      individuals without and with cognitive impairment prefers to be informed about a
      diagnosis of dementia for reasons pertaining to autonomy.

PMID- 24933480
TI  - You keep using that term.

PMID- 24933481
TI  - NOTCH and PTEN in prostate cancer.
AB  - Over the past decade, our understanding of the role that Notch-signaling has in
      tumorigenesis has shifted from leukemogenesis into cancers of solid tumors.
      Emerging data suggests that in addition to direct effects mediated through the
      canonical Notch pathway, Notch may participate in epithelial tumor development
      through regulation of pathways such as PTEN/PI3K/Akt. Prostate cancer is a
      disease for which PTEN gene expression is especially essential. This review will
      summarize a role for Notch in prostate development and cancer with an emphasis on
      how the Notch pathway may intersect with PTEN/PI3K/Akt and mTOR signaling. 

PMID- 24933482
TI  - The Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ)
      revised: item response analysis and concurrent validity.
AB  - OBJECTIVE: Childhood cancer survivors are at risk for neurocognitive impairment
      related to cancer diagnosis or treatment. This study refined and further
      validated the Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS
      NCQ; Krull et al., 2008), a scale developed to screen for impairment in long-term
      survivors of childhood cancer. METHOD: Items related to task efficiency, memory,
      organization, and emotional-regulation domains were examined using item response
      theory (IRT). Data were collected from 833 adult survivors of childhood cancer
      who completed self-report and direct neurocognitive testing for the St. Jude
      Lifetime Cohort Study. The revision process included: (a) content-validity
      mapping of items to domains, (b) constructing a revised CCSS-NCQ, (c) selecting
      items within specific domains using IRT, and (d) evaluating concordance between
      the revised CCSS-NCQ and direct neurocognitive assessment. RESULTS: Using content
      and measurement properties, 32 items were retained (8 items in 4 domains). Items
      captured low to middle levels of neurocognitive concerns. The latent domain
      scores demonstrated poor convergent/divergent validity with the direct
      assessments. Adjusted ESs (ES; Cohen's d) for agreement between self-reported
      memory and direct memory assessment were moderate for total recall (ES = 0.66),
      long-term memory (ES = 0.63), and short-term memory (STM; ES = 0.55). ESs between
      self-rated task efficiency and direct assessment of attention were moderate for
      focused attention (ES = 0.70) and attention span (ES = 0.50), but small for
      sustained attention (ES = 0.36). Cranial radiation therapy and female gender were
      associated with lower self-reported neurocognitive function. CONCLUSION: The
      revised CCSS-NCQ demonstrates adequate measurement properties for assessing day
      to-day neurocognitive concerns in childhood cancer survivors, and adds useful
      information to direct assessment.

PMID- 24933484
TI  - Unilateral hand contractions produce motivational biases in social economic
      decision making.
AB  - OBJECTIVE: Unilateral hand contractions have been shown to induce relative
      activation of the contralateral hemisphere, which is in turn associated with
      distinct motivational states. Specifically, right hand contraction increases
      relative left activation and promotes an approach state, and left hand
      contractions promote relative right activation and withdrawal states. Using the
      same hand clenching technique, the present study extends this research to examine
      the incidental role of motivational tendency on interactive economic decision
      making. METHOD: A total of 75 right-handed participants were randomly assigned to
      1 of 3 conditions, including withdrawal/left-hand contractions, approach/right
      hand contractions, and control/no contraction. Participants completed 2 well
      known economic tasks, namely the Ultimatum Game (UG), Dictator Game (DG).
      RESULTS: In the UG, we found that relative to individuals in the withdrawal
      condition, those in the approach (right-hand contraction) condition made higher
      monetary offers to human partners who could either accept or reject these offers.
      Moreover, those in the approach condition rejected significantly more unfair
      offers from human partners. CONCLUSIONS: This study provides the first evidence
      that hemispheric activation, using unilateral muscle contractions, may play a
      causal role in biasing social economic decision making. Overall, there results
      suggest that greater relative left frontal activation promotes reward-maximizing
      strategies, consistent with an approach motivation, and relative right frontal
      activation may decrease such strategic tendencies.

PMID- 24933483
TI  - Life experience and demographic influences on cognitive function in older adults.
AB  - OBJECTIVE: We examined the influence of a broad spectrum of life experiences on
      longitudinal cognitive trajectories in a demographically diverse sample of older
      adults. METHOD: Participants were 333 educationally, ethnically, and cognitively
      diverse older adults enrolled in a longitudinal aging study. Mixed-effects
      regression was used to measure baseline status in episodic memory, executive
      functioning, and semantic memory and change in a global cognition factor defined
      by change in these 3 domain-specific measures. We examined effects of life
      experience variables (literacy, childhood socioeconomic status, morphometric
      measures of physical development, life course physical and recreational activity)
      on longitudinal cognitive trajectories, covarying for age, apolipoprotein E
      (APOE) genotype and demographics (education, ethnicity, language). RESULTS: Non
      Latino Whites had higher baseline cognition, but life experience variables
      attenuated ethnic differences in cognitive scores. Age, literacy, childhood
      socioeconomic status, and physical activity significantly influenced baseline
      cognition. Age, APOE epsilon4, and decline in intellectually and socially
      stimulating recreational activity from mid to late life were independently
      associated with increased late life cognitive decline. Higher literacy and late
      life recreational activity were associated with less decline. Literacy had
      similar effects for English and Spanish readers/speakers. Bilingual English and
      Spanish speakers did not differ from English Speakers in cognitive performance.
      CONCLUSIONS: Life experience variables, especially literacy level, were strongly
      related to baseline cognition and substantially attenuated effects of
      race/ethnicity and education. Cognitive change was best explained by age, APOE
      epsilon4, literacy, and current recreational activities. Literacy had robust
      associations with baseline cognition and cognitive change in both English and
      Spanish speakers.

PMID- 24933485
TI  - Assessment of functional change and cognitive correlates in the progression from
      healthy cognitive aging to dementia.
AB  - OBJECTIVE: There is currently limited understanding of the course of change in
      everyday functioning that occurs with normal aging and dementia. To better
      characterize the nature of this change, we evaluated the types of errors made by
      participants as they performed everyday tasks in a naturalistic environment.
      METHOD: Participants included cognitively healthy younger adults (YA; n = 55) and
      older adults (OA; n = 88), and individuals with mild cognitive impairment (MCI: n
      = 55) and dementia (n = 18). Participants performed 8 scripted everyday
      activities (e.g., filling a medication dispenser) while under direct observation
      in a campus apartment. Task performances were coded for the following errors:
      inefficient actions, omissions, substitutions, and irrelevant actions. RESULTS:
      Performance accuracy decreased with age and level of cognitive impairment.
      Relative to the YAs, the OA group exhibited more inefficient actions which were
      linked to performance on neuropsychological measures of executive functioning.
      Relative to the OAs, the MCI group committed significantly more omission errors
      which were strongly linked to performance on memory measures. All error types
      were significantly more prominent in individuals with dementia. Omission errors
      uniquely predicted everyday functional status as measured by both informant
      report and a performance-based measure. CONCLUSIONS: These findings suggest that
      in the progression from healthy aging to MCI, everyday task difficulties may
      evolve from task inefficiencies to task omission errors, leading to inaccuracies
      in task completion that are recognized by knowledgeable informants. Continued
      decline in cognitive functioning then leads to more substantial everyday errors,
      which compromise ability to live independently.

PMID- 24933486
TI  - An empirical comparison of the therapeutic benefits of physical exercise and
      cognitive training on the executive functions of older adults: a meta-analysis of
      controlled trials.
AB  - A robust body of aging-related research has established benefits of both physical
      exercise (PE) and cognitive training (CT) on executive functions related to the
      activities of daily living of older adults; however, no meta-analysis has
      compared these treatments. OBJECTIVE: The current quantitative review involved a
      comparison of the overall effect sizes of PE and CT interventions on executive
      functions (Morris, 2008; pre-post-controlled effect size: d(ppc)), while also
      exploring contextual moderators of treatment outcomes. METHOD: A systematic
      review identified 46 studies (23 PE, 21 CT, and 2 both) meeting inclusion
      criteria (i.e., controlled interventions, executive-related outcomes, mean ages
      65+, information to calculate d(ppc)). RESULTS: The weighted mean dppc values
      came to 0.12 (p < .01) for PE and 0.24 (p < .01) for CT. Treatment effects
      differed based on executive constructs for CT, with problem solving presenting
      the highest d(ppc) (0.47, p < .01). Notably, PE produced similar effect sizes
      across distinct executive functions. Treatment characteristics (e.g., session
      length/frequency) did not predict effect sizes. CT had a significant benefit on
      healthy participants (0.26, p < .01), but cognitively impaired samples did not
      experience a significant effect. CONCLUSIONS: Both treatments improved executive
      functions, but CT presented a potential advantage at improving executive
      functions. Improvements in executive functions differed depending on construct
      for CT, whereas each construct produced similar, modest effect sizes for PE.
      Publication bias and study quality variability potentially bias these
      conclusions, as lower quality studies likely produced inflated effect sizes.

PMID- 24933487
TI  - Visual encoding impairment in patients with schizophrenia: contribution of
      reduced working memory span, decreased processing speed, and affective symptoms.
AB  - OBJECTIVE: Previous research has revealed the contribution of decreased
      processing speed and reduced working memory span in verbal and visual memory
      impairment in patients with schizophrenia. The role of affective symptoms in
      verbal memory has also emerged in a few studies. The authors designed a picture
      recognition task to investigate the impact of these factors on visual encoding.
      METHOD: Two types of pictures (black and white vs. colored) were presented under
      2 different conditions of context encoding (either displayed at a specific
      location or in association with another visual stimulus). It was assumed that the
      process of encoding associated pictures was more effortful than that of encoding
      pictures that were presented alone. Working memory span and processing speed were
      assessed. RESULTS: In the patient group, working memory span was significantly
      associated with the recognition of the associated pictures but not significantly
      with that of the other pictures. Controlling for processing speed eliminated the
      patients' deficit in the recognition of the colored pictures and greatly reduced
      their deficit in the recognition of the black-and-white pictures. The recognition
      of the black-and-white pictures was inversely related to anxiety in men and to
      depression in women. CONCLUSIONS: Working memory span constrains the effortful
      visual encoding processes in patients, whereas processing speed decrement
      accounts for most of their visual encoding deficit. Affective symptoms also have
      an impact on visual encoding, albeit differently in men and women.

PMID- 24933488
TI  - Cognitive impairment in adult ADHD--perspective matters!
AB  - OBJECTIVE: The assessment of cognitive functions of adults with attention deficit
      hyperactivity disorder (ADHD) comprises self-ratings of cognitive functioning
      (subjective assessment) as well as psychometric testing (objective
      neuropsychological assessment). The aim of the present study was to explore the
      utility of these assessment strategies in predicting neuropsychological
      impairments of adults with ADHD as determined by both approaches. METHOD: Fifty
      five adults with ADHD and 66 healthy participants were assessed with regard to
      cognitive functioning in several domains by employing subjective and objective
      measurement tools. Significance and effect sizes for differences between groups
      as well as the proportion of patients with impairments were analyzed.
      Furthermore, logistic regression analyses were carried out in order to explore
      the validity of subjective and objective cognitive measures in predicting
      cognitive impairments. RESULTS: Both subjective and objective assessment tools
      revealed significant cognitive dysfunctions in adults with ADHD. The majority of
      patients displayed considerable impairments in all cognitive domains assessed. A
      comparison of effect sizes, however, showed larger dysfunctions in the subjective
      assessment than in the objective assessment. Furthermore, logistic regression
      models indicated that subjective cognitive complaints could not be predicted by
      objective measures of cognition and vice versa. CONCLUSIONS: Subjective and
      objective assessment tools were found to be sensitive in revealing cognitive
      dysfunctions of adults with ADHD. Because of the weak association between
      subjective and objective measurements, it was concluded that subjective and
      objective measurements are both important for clinical practice but may provide
      distinct types of information and capture different aspects of functioning.

PMID- 24933489
TI  - Discrimination and recognition of facial expressions of emotion and their links
      with voluntary control of facial musculature in Parkinson's disease.
AB  - OBJECTIVE: To explore perception of facial expressions of emotion and its link
      with voluntary facial musculature control in Parkinson's disease (PD). METHOD: We
      investigated in 2 sets of experiments in PD patients and healthy controls the
      perceptual ability to discriminate (a) graded intensities of emotional from
      neutral expressions, (b) graded intensities of the same emotional expressions,
      (c) full-blown discrepant emotional expressions from 2 similar expressions and
      the more complex recognition ability to label full-blown emotional expressions.
      We tested an embodied simulationist account of emotion perception in PD, which
      predicts a link between the ability to perceive emotional expressions and facial
      musculature control. We also explored the contribution of the ability to extract
      facial information (besides emotion) to emotion perception in PD. RESULTS: Those
      with PD were, as a group, impaired relative to controls (with large effect sizes)
      in all measures of discrimination and recognition of emotional expressions,
      although some patients performed as well as the best performing controls. In
      support of embodied simulation, discrimination and recognition of emotional
      expressions correlated positively with voluntary control of facial musculature
      (after partialing out disease severity and age). Patients were also impaired at
      extracting information other than emotion from faces, specifically discriminating
      and recognizing identity from faces (with large effect sizes); identity
      discrimination correlated positively with emotion discrimination and recognition
      but not with voluntary facial musculature control (after partialing out disease
      severity and age). CONCLUSIONS: The results indicate that impaired sensory and
      sensorimotor processes, which are a function of disease severity, affect emotion
      perception in PD.

PMID- 24933490
TI  - Preserved meaning in the context of impaired naming in temporal lobe epilepsy.
AB  - OBJECTIVE: Word-finding difficulties are a common complaint among individuals
      with left (domain) temporal lobe epilepsy (TLE). We tested the hypothesis that
      these difficulties stem from a deficit in semantic processing. METHOD: We tested
      and compared semantic processing in left and right TLE patients and healthy
      controls. To avoid the confound of word retrieval, we used two semantic tasks
      (semantic priming and picture-matching) that did not require spoken word
      production. In addition to accuracy, we recorded response time in an effort to
      achieve a sensitive assessment of semantic processing. RESULTS: Semantic priming
      was in all respects comparable between left TLE patients with documented word
      finding difficulty and right TLE patients without word-finding difficulty.
      Likewise, performances were comparable between groups on picture matching, which
      demanded knowledge of detailed semantic features for decisions regarding subtle
      differences in semantic relatedness. CONCLUSIONS: Overall, these results, which
      demonstrate a relative preservation of semantic processing in left TLE, suggest
      that the probable cause of word-finding difficulty in this group relates to
      processes that follow semantic retrieval in word production, involving the
      retrieval of lexical/phonological information. In addition to clinical
      implications for remediation, these results refine our understanding of the
      neurocognitive organization of temporal mechanisms supporting spoken word
      production.

PMID- 24933491
TI  - Hyperconnectivity is a fundamental response to neurological disruption.
AB  - OBJECTIVE: In the cognitive and clinical neurosciences, the past decade has been
      marked by dramatic growth in a literature examining brain "connectivity" using
      noninvasive methods. We offer a critical review of the blood oxygen level
      dependent functional MRI (BOLD fMRI) literature examining neural connectivity
      changes in neurological disorders with focus on brain injury and dementia. The
      goal is to demonstrate that there are identifiable shifts in local and large
      scale network connectivity that can be predicted by the degree of pathology. We
      anticipate that the most common network response to neurological insult is
      hyperconnectivity but that this response depends upon demand and resource
      availability. METHOD: To examine this hypothesis, we initially reviewed the
      results from 1,426 studies examining functional brain connectivity in individuals
      diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive
      impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126
      studies were included for detailed analysis. RESULTS: RESULTS from 126 studies
      examining local and whole brain connectivity demonstrated increased connectivity
      in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with
      findings in mild cognitive impairment and Alzheimer's disease where there is a
      shift to diminished connectivity as degeneration progresses. CONCLUSION: This
      summary of the functional imaging literature using fMRI methods reveals that
      hyperconnectivity is a common response to neurological disruption and that it may
      be differentially observable across brain regions. We discuss the factors
      contributing to both hyper- and hypoconnectivity results after neurological
      disruption and the implications these findings have for network plasticity.

PMID- 24933493
TI  - Team-based care to improve blood pressure control: recommendation of the
      Community Preventive Services Task Force.

PMID- 24933492
TI  - Does bilingualism contribute to cognitive reserve? Cognitive and neural
      perspectives.
AB  - OBJECTIVE: Cognitive reserve refers to how individuals actively utilize neural
      resources to cope with neuropathology to maintain cognitive functioning. The
      present review aims to critically examine the literature addressing the
      relationship between bilingualism and cognitive reserve to elucidate whether
      bilingualism delays the onset of cognitive and behavioral manifestations of
      dementia. Potential neural mechanisms behind this relationship are discussed.
      METHOD: PubMed and PsycINFO databases were searched (through January 2014) for
      original research articles in English or Spanish languages. The following search
      strings were used as keywords for study retrieval: "bilingual AND reserve,"
      "reserve AND neural mechanisms," and "reserve AND multilingualism." RESULTS:
      Growing scientific evidence suggests that lifelong bilingualism contributes to
      cognitive reserve and delays the onset of Alzheimer's disease symptoms, allowing
      bilingual individuals affected by Alzheimer's disease to live an independent and
      richer life for a longer time than their monolingual counterparts. Lifelong
      bilingualism is related to more efficient use of brain resources that help
      individuals maintain cognitive functioning in the presence of neuropathology. We
      propose multiple putative neural mechanisms through which lifelong bilinguals
      cope with neuropathology. The roles of immigration status, education, age of
      onset, proficiency, and frequency of language use on the relationship between
      cognitive reserve and bilingualism are considered. CONCLUSIONS: Implications of
      these results for preventive practices and future research are discussed.

PMID- 24933495
TI  - Quantitative analysis of neonicotinoid insecticide residues in foods: implication
      for dietary exposures.
AB  - This study quantitatively measured neonicotinoids in various foods that are
      common to human consumption. All fruit and vegetable samples (except nectarine
      and tomato) and 90% of honey samples were detected positive for at least one
      neonicotinoid; 72% of fruits, 45% of vegetables, and 50% of honey samples
      contained at least two different neonicotinoids in one sample, with imidacloprid
      having the highest detection rate among all samples. All pollen samples from New
      Zealand contained multiple neonicotinoids, and five of seven pollens from
      Massachusetts detected positive for imidacloprid. These results show the
      prevalence of low-level neonicotinoid residues in fruits, vegetables, and honey
      that are readily available in the market for human consumption and in the
      environment where honeybees forage. In light of new reports of toxicological
      effects in mammals, the results strengthen the importance of assessing dietary
      neonicotinoid intakes and the potential human health effects. 

PMID- 24933496
TI  - RCT of a brief phone-based CBT intervention to improve PTSD treatment utilization
      by returning service members.
AB  - OBJECTIVES: Many service members do not seek care for mental health and addiction
      problems, often with serious consequences for them, their families, and their
      communities. This study tested the effectiveness of a brief, telephone-based,
      cognitive-behavioral intervention designed to improve treatment engagement among
      returning service members who screened positive for posttraumatic stress disorder
      (PTSD). METHODS: Service members who had served in Operation Enduring Freedom or
      Operation Iraqi Freedom who screened positive for PTSD but had not engaged in
      PTSD treatment were recruited (N=300), randomly assigned to either control or
      intervention conditions, and administered a baseline interview. Intervention
      participants received a brief cognitive-behavioral therapy intervention;
      participants in the control condition had access to usual services. All
      participants received follow-up phone calls at months 1, 3, and 6 to assess
      symptoms and service utilization. RESULTS: Participants in both conditions had
      comparable rates of treatment engagement and PTSD symptom reduction over the
      course of the six-month trial, but receiving the telephone-based intervention
      accelerated service utilization (treatment engagement and number of sessions) and
      PTSD symptom reduction. CONCLUSIONS: A one-time brief telephone intervention can
      engage service members in PTSD treatment earlier than conventional methods and
      can lead to immediate symptom reduction. There were no differences at longer-term
      follow-up, suggesting the need for additional intervention to build upon initial
      gains.

PMID- 24933497
TI  - The use of banquettes of Posidonia oceanica as a source of fiber and minerals in
      ruminant nutrition. An observational study.
AB  - In the search for new food sources that contribute to the optimization of
      livestock production this paper discusses the possibility of using waste (called
      banquettes) of a marine plant commonly found on the Mediterranean coasts:
      Posidonia oceanica. The idea stems from the use of a waste that in summertime
      generates large costs because it is considered bothersome on the beaches. Thus,
      tons and tons of residues are collected each year from the beach, being destined
      for incineration. However, alternative uses for these residues are suggested,
      such as forage that is particularly relevant for the Mediterranean coast, where
      the weather does not support abundant grass growth. With this purpose, samples of
      banquettes of P. oceanica from six different points of a touristic place located
      in the Murcia Region (S.E. of Spain) were collected in April 2012 on the same day
      directly from the beach above the water line, washed with distilled water and sun
      dried for 48 h. Approximately 500 g of each sample of plant material was chopped
      and two subsamples of 200 g each were placed in airtight plastic containers and
      sent to the laboratory for mineral and chemical analysis. This report provides
      data on the nutritional composition of P. oceanica such as mineral contents (As,
      Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn) and chemical composition (ash, CP, ether
      extract (EE), NDF and ADF, respectively) and ADL. Finally, the in sacco rumen
      disappearance of dry matter (DM), organic matter (OM), CP and NDF were studied.
      Our results showed that minerals, except for Fe, where within the range of values
      reported for P. oceanica in other parts of the Mediterranean region. Given the
      high Fe content further studies assessing the antagonic Fe-Cu interaction and its
      effect on animal health should be addressed. In relation to chemical composition,
      it is clear that this seagrass is a poor protein source and has levels of DM
      degradability at 24 h, similar to those obtained for cereal straw. The
      information summarized here shows some potential for the use of banquettes of P.
      oceanica as forage source in ruminant nutrition.

PMID- 24933498
TI  - Enantioselective ruthenium(II)/Xyl-SunPhos/Daipen-catalyzed hydrogenation of
      gamma-ketoamides.
AB  - A series of gamma-hydroxy amides were synthesized with high enantioselectivities
      (up to 99%) using asymmetric hydrogenation of the corresponding gamma-ketoamides
      in the presence of Ru-Xyl-SunPhos-Daipen catalyst providing key building blocks
      for a variety of naturally occurring and biologically active compounds. 

PMID- 24933494
TI  - Team-based care and improved blood pressure control: a community guide systematic
      review.
AB  - CONTEXT: Uncontrolled hypertension remains a widely prevalent cardiovascular risk
      factor in the U.S. team-based care, established by adding new staff or changing
      the roles of existing staff such as nurses and pharmacists to work with a primary
      care provider and the patient. Team-based care has the potential to improve the
      quality of hypertension management. The goal of this Community Guide systematic
      review was to examine the effectiveness of team-based care in improving blood
      pressure (BP) outcomes. EVIDENCE ACQUISITION: An existing systematic review
      (search period, January 1980-July 2003) assessing team-based care for BP control
      was supplemented with a Community Guide update (January 2003-May 2012). For the
      Community Guide update, two reviewers independently abstracted data and assessed
      quality of eligible studies. EVIDENCE SYNTHESIS: Twenty-eight studies in the
      prior review (1980-2003) and an additional 52 studies from the Community Guide
      update (2003-2012) qualified for inclusion. Results from both bodies of evidence
      suggest that team-based care is effective in improving BP outcomes. From the
      update, the proportion of patients with controlled BP improved (median
      increase=12 percentage points); systolic BP decreased (median reduction=5.4
      mmHg); and diastolic BP also decreased (median reduction=1.8 mmHg). CONCLUSIONS:
      Team-based care increased the proportion of people with controlled BP and reduced
      both systolic and diastolic BP, especially when pharmacists and nurses were part
      of the team. Findings are applicable to a range of U.S. settings and population
      groups. Implementation of this multidisciplinary approach will require health
      system-level organizational changes and could be an important element of the
      medical home.

PMID- 24933500
TI  - Relationship between modified CT severity index and clinical features of L
      asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia.
AB  - PURPOSE: To describe clinical and CT features of L-asparaginase-associated
      pancreatitis (L-AP) and to correlate CT grades with clinical parameters. METHODS:
      A total of 16 children (M:F = 9:7; mean age, 8.1 years) who developed L-AP after
      L-asparaginase (L-asp) treatment and underwent abdominal CT scan were included.
      We retrospectively reviewed clinical data (age, sex, signs, and symptoms related
      to pancreatic toxicity and its complications, the number of L-asp doses receiving
      before L-AP); laboratory test results (serum amylase, lipase, C-reactive protein
      (CRP), calcium, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), aspartate
      aminotransferase (AST), glucose, and serum albumin); and clinical course (the
      number of days of hospitalization, number of NPO days, use of nasogastric tube,
      intravenous (IV) narcotics, total parenteral nutrition (TPN) or any surgical
      intervention). We also reviewed CT images and modified CT severity index (MCSI)
      for grading the severity of AP and classified to three groups (mild, moderate,
      and severe) or two groups (low and high score) according to MCSI. RESULTS: L-AP
      typically occurred early in the course of therapy. Use of IV narcotics (P = .014)
      and peak amylase (P = .009) showed a significant difference between mild and
      severe L-AP groups according to MCSI. Between the low and high score groups, Use
      of IV narcotics (P = .046), BUN (P = .039), and peak amylase level (P = .013) was
      significantly different. However, the L-asp dose, hospital day, and other
      clinical date associated with prognosis did not show any significant difference.
      CONCLUSION: In L-AP with pediatric ALL patients, MCSI may correlate with usage of
      IV narcotics, BUN, and peak amylase levels.

PMID- 24933501
TI  - Motor learning during poststroke gait rehabilitation: a case study.
AB  - INTRODUCTION: To develop more effective gait rehabilitation strategies, it is
      important to understand the time course of motor learning that underlies
      improvements achieved with gait training. The purpose of this case study was to
      evaluate motor learning through the measurement of within-session and across
      session changes in gait biomechanics during the first and sixth weeks of a 6-week
      clinical gait training program. CASE DESCRIPTION: A 47-year-old man with
      poststroke left hemiparesis participated in the study (15.5 months poststroke,
      lower extremity Fugl-Meyer score of 12). INTERVENTION: The subject participated
      in 6 weeks of training with 3 sessions per week, comprising fast treadmill
      walking and functional electrical stimulation to plantar and dorsiflexors. In one
      training session during the first and sixth weeks, paretic propulsion and swing
      phase knee flexion were measured during a pretest (before the training session),
      posttest (after the training session), and retention test (48 hours after
      training). OUTCOMES: After 6 week of training, the subject's gait speed increased
      from 0.38 to 0.57 m/s; there was a 55.4% improvement in paretic propulsion and
      25% increase in swing phase knee flexion. Examination of change scores revealed
      greater within-session gains and greater retention during the first versus sixth
      weeks of gait training for both paretic propulsion and knee flexion. DISCUSSION:
      We demonstrate the feasibility and advantage of using within- and across-session
      changes for evaluating motor learning during clinical gait rehabilitation. An
      understanding of the time course of motor learning that underlies gait training
      can guide the development of novel strategies and dosing regimens to increase the
      efficacy of each session of gait rehabilitation. VIDEO ABSTRACT AVAILABLE: (See
      Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A72, for more
      insights from the authors.).

PMID- 24933503
TI  - Children's (in)dependent mobility in Portugal.
AB  - OBJECTIVES: To characterize children's independent mobility in Portugal, by
      studying the influence of age, sex, school type (primary/secondary) and location
      (urban/rural). To explore associations between mobility licences and children's
      actual independent mobility. DESIGN: Cross-sectional study of 1099 children
      between 8 and 15 years of age and their parents. Children attended primary
      (n=660, 49% boys, 69% urban) and secondary (n=439, 43% boys, 72% urban) schools.
      METHODS: The Portuguese version of the child independent mobility survey (Policy
      Studies Institute, London) was completed. Parents reported the mobility licences
      granted to their children. Children reported their independent mobility on school
      journeys and on weekends. Differences were examined in mobility licences and
      independent mobility by sex, urban/rural setting and primary/secondary schools.
      Multiple logistic regression models examined the associations between different
      variables and actual independent mobility. RESULTS: Secondary school children are
      granted more licences and have greater levels of independent mobility than
      primary school children. Only 21% of primary school children and 45% of secondary
      school children come home from school actively and independently. Overall, sex
      does not influence the licences granted to children in Portugal but boys have
      greater levels of independent mobility during the weekends than girls. Children
      in rural settings report engaging in more activities during the weekend. The
      number of mobility licences granted to the child was identified as predictor for
      actual independent mobility on school days and during the weekend. CONCLUSIONS:
      Portuguese children lack independent mobility. Complementary qualitative research
      will be important to inform about the better practices to tackle this problem.

PMID- 24933504
TI  - Retrospective analysis of anthropometric and fitness characteristics associated
      with long-term career progression in Rugby League.
AB  - OBJECTIVES: The current study retrospectively investigated the differences in
      anthropometric and fitness characteristics of junior rugby league players
      selected onto a talent identification and development (TID) programme between
      long-term career progression levels (i.e., amateur, academy, professional).
      DESIGN: Retrospective design. METHODS: Former junior rugby league players (N=580)
      selected to a TID programme were grouped according to their career progression
      level. Anthropometric (height, sitting height, body mass and sum of four
      skinfolds), maturational and fitness (power, speed, change of direction speed and
      estimated VO2max) assessments were conducted at 13-15 years. Multivariate
      analysis of covariance (MANCOVA) analyzed differences between career progression
      levels controlling for chronological age. RESULTS: 57.1% and 12.1% of players
      selected to the TID programme progressed to academy and professional levels in
      rugby league, respectively. Sum of four skinfolds (eta(2)=0.03), vertical jump
      (eta(2)=0.02), 10 m (eta(2)=0.02), 20 m (eta(2)=0.02), 30 m (eta(2)=0.02), and 60
      m (eta(2)=0.03) speed, agility 505 left (eta(2)=0.06), agility 505 right
      (eta(2)=0.05) and estimated VO2max (eta(2)=0.03) were superior within junior
      players who progressed to professional compared to amateur levels. No significant
      differences were identified between future academy and professional players for
      any measure. CONCLUSIONS: Findings suggest that lower sum of four skinfolds and
      advanced fitness characteristics within junior (13-15 years) rugby league players
      may partially contribute to long-term career progression. Therefore, TID
      programmes within rugby league should aim to assess and develop body composition
      and fitness characteristics, especially change of direction speed. However, TID
      programmes should also consider technical, tactical and psycho-social
      characteristics of junior rugby league players that may be important for long
      term career progression.

PMID- 24933499
TI  - Nitric oxide signaling in the development and evolution of language and cognitive
      circuits.
AB  - The neocortex underlies not only remarkable motor and sensory capabilities, but
      also some of our most distinctly human cognitive functions. The emergence of
      these higher functions during evolution was accompanied by structural changes in
      the neocortex, including the acquisition of areal specializations such as Broca's
      speech and language area. The study of these evolutionary mechanisms, which
      likely involve species-dependent gene expression and function, represents a
      substantial challenge. These species differences, however, may represent valuable
      opportunities to understand the molecular underpinnings of neocortical evolution.
      Here, we discuss nitric oxide signaling as a candidate mechanism in the assembly
      of neocortical circuits underlying language and higher cognitive functions. This
      hypothesis was based on the highly specific mid-fetal pattern of nitric oxide
      synthase 1 (NOS1, previously nNOS) expression in the pyramidal (projection)
      neurons of two human neocortical areas respectively involved in speech and
      language, and higher cognition; the frontal operculum (FOp) and the anterior
      cingulate cortex (ACC). This expression is transiently present during mid
      gestation, suggesting that NOS1 may be involved in the development of these areas
      and the assembly of their neural circuits. As no other gene product is known to
      exhibit such exquisite spatiotemporal expression, NOS1 represents a remarkable
      candidate for these functions. 

PMID- 24933505
TI  - The diagnostic utility of clinical tests for differentiating between cervicogenic
      and other causes of dizziness after a sports-related concussion: An international
      Delphi study.
AB  - OBJECTIVES: Dizziness after a sports-related concussion is very common and is
      associated with prolonged recovery. The events in sports that cause concussion
      include strong mechanical forces exerted to the head and neck, potentially
      injuring the cervical region, the peripheral vestibular and central nervous
      system, all of which can contribute to a sensation of dizziness. The purpose of
      this study was to identify proper clinically administered tests and measures that
      are useful in differentiating between cervicogenic and other causes of dizziness
      after a sports-related concussion. DESIGN: The Delphi method. METHODS: The
      workgroup identified the initial list of suggested clinical tests and the initial
      list of content experts on dizziness and/or concussion through a search of peer
      reviewed and grey literature. The respondent group included all invited experts
      who opted to participate. A sequential three-round process was used for
      elicitation of consensus opinions from the targeted content experts. RESULTS: The
      respondent group included 25 members from several medical disciplines who were
      experts in concussion and dizziness. At the conclusion of the study, ten clinical
      tests achieved the designation of strong clinical utility, six were determined to
      have weak clinical utility and seven achieved no consensus among the experts.
      CONCLUSIONS: The majority of clinical tests identified as having strong clinical
      utility are tests used to identify dizziness originating from the vestibular or
      central nervous system. No clinical tests specific for the cervical region
      achieved consensus. Expert opinion from different medical professions and even
      within professions was widely divergent regarding the utility of clinical tests
      to assess cervical dysfunction.

PMID- 24933506
TI  - LIM proteins in actin cytoskeleton mechanoresponse.
AB  - The actin cytoskeleton assembles into branched networks or bundles to generate
      mechanical force for critical cellular processes such as establishment of
      polarity, adhesion, and migration. Stress fibers (SFs) are contractile actomyosin
      structures that physically couple to the extracellular matrix through integrin
      based focal adhesions (FAs), thereby transmitting force into and across the cell.
      Recently, LIN-11, Isl1, and MEC-3 (LIM) domain proteins have been implicated in
      mediating this cytoskeletal mechanotransduction. Among the more well-studied LIM
      domain adapter proteins is zyxin, a dynamic component of both FAs and SFs. Here
      we discuss recent research detailing the mechanisms by which SFs adjust their
      structure and composition to balance mechanical forces and suggest ways that
      zyxin and other LIM domain proteins mediate mechanoresponse. 

PMID- 24933507
TI  - Synthesis and evaluation of three structurally related 18F-labeled orvinols of
      different intrinsic activities: 6-O-[18F]fluoroethyl-diprenorphine ([18F]FDPN), 6
      O-[18F]fluoroethyl-buprenorphine ([18F]FBPN), and 6-O-[18F]fluoroethyl-phenethyl
      orvinol ([18F]FPEO).
AB  - We report the synthesis and biological evaluation of a triplet of 6-O-(18)F
      fluoroethylated derivatives of structurally related orvinols that span across the
      full range of intrinsic activities, the antagonist diprenorphine, the partial
      agonist buprenorphine, and the full agonist phenethyl-orvinol. [(18)F]fluoroethyl
      diprenorphine, [(18)F]fluoroethyl-buprenorphine, and [(18)F]fluoroethyl-phenethyl
      orvinol were prepared in high yields and quality from their 6-O-desmethyl
      precursors. The results indicate suitable properties of the three 6-O-(18)F
      fluoroethylated derivatives as functional analogues to the native carbon-11
      labeled versions with similar pharmacological properties. 

PMID- 24933508
TI  - Genetic differences in the rat lungworm, Angiostrongylus cantonensis (Nematoda:
      Angiostrongylidae), in Thailand.
AB  - This study surveyed the genetic differences among Angiostrongylus cantonensis (A.
      cantonensis) using the mitochondrial cytochrome b (cytb) gene. Partial cytb
      sequences were determined for 91 worms from eight locations in Thailand. Using
      morphological techniques, the nematodes were found to be A. cantonensis.
      Phylogenetic analysis found two main clades, which were subdivided into four
      subclades (clusters). Haplotype network analysis showed that 11 distinct cytb
      haplotypes were also present in four groups of A. cantonensis. There was no
      observable relationship between the genetic differentiation of gene flow and
      geographical distance. This low genetic variation and geographical distribution
      of A. cantonensis in each location indicates a founder effect, which may have
      resulted from multiple independent origins, and suggests that haplotypes migrated
      from endemic areas via human-related activities. 

PMID- 24933510
TI  - In situ synthesis of size-controlled, stable silver nanoparticles within
      ultrashort peptide hydrogels and their anti-bacterial properties.
AB  - We have developed a silver-releasing biomaterial with promising potential for
      wound healing applications. The material is made of ultrashort peptides which can
      self-assemble in water to form hydrogels. Silver nanoparticles (Ag NPs) were
      synthesized in situ within the biomaterial, using only UV irradiation and no
      additional chemical reducing agents. The synthetic strategy allows precise
      control of the nanoparticle size, with the network of peptide fibers preventing
      aggregation of Ag NPs. The biomaterial shows increased mechanical strength
      compared to the hydrogel control. We observed a sustained release of Ag NPs over
      a period of 14 days. This is a crucial prerequisite for effective anti-bacterial
      therapy. The ability to inhibit bacterial growth was tested using different
      bacterial strains, namely gram-negative Escherichia coli and Pseudomonas
      aeruginosa and gram-positive Staphylococcus aureus. Inhibition of bacterial
      growth was observed for all strains. The best results were obtained for
      Pseudomonas aeruginosa which is known for exhibiting multidrug resistance.
      Biocompatibility studies on HDFa cells, using Ag NP-containing hydrogels, did not
      show any significant influence on cell viability. We propose this silver
      releasing hydrogel as an excellent biomaterial with great potential for
      applications in wound healing due to its low silver content, sustained silver
      nanoparticle release and biocompatibility. 

PMID- 24933511
TI  - The effect of oral administration of iron saturated-bovine lactoferrin
      encapsulated chitosan-nanocarriers on osteoarthritis.
AB  - Osteoarthritis (OA) treatments have major limitations which include systemic
      toxicity, reduced joint retention and inability to inhibit disease progression.
      In this study, the therapeutic potentials of 100% iron saturated-bovine
      lactoferrin encapsulated in alginate-chitosan polymeric nanocarriers (AEC-CP-Fe
      bLf-NCs) were examined in in vitro inflammatory OA model and in collagen-induced
      arthritis (CIA) mice. By diminishing IL-1beta induced apoptotic and oxidative
      stress, chondrocyte protection and proliferation was up-regulated with C-CP-Fe
      bLf-NCs as compared to void and C-CP-Apo(metal free)-bLf-NCs. Oral administration
      of nanocarriers in mice was non-toxic and it significantly induced disease
      modifying activity by reducing joint inflammation and significantly
      downregulating the expression of catabolic genes, IL-1beta, NO, JNK and MAPK. In
      addition, up-regulation of type II collagen, aggrecan and inflammation depleted
      iron and calcium metabolisms via inhibition of miRNA of iron transporting
      receptors was shown in AEC-CP-Fe-bLf-NCs treated mice. In addition, AEC-CP-Fe-bLf
      NCs dissoluted calcium pyrophosphate crystals found in mice joints indicating the
      significantly important therapeutic ability of nanoformulated Fe-bLf to be
      utilized in the treatment of chronic inflammatory rheumatic diseases such as OA. 

PMID- 24933512
TI  - Vitrified collagen-based conjunctival equivalent for ocular surface
      reconstruction.
AB  - The main functions of the conjunctiva, an essential part of the ocular surface,
      are to maintain the equilibrium of the tear film and to protect the eye. Upon
      injuries, the prerequisite to successful ocular surface repair is conjunctival
      reconstruction. Tissue engineering techniques, including transplantation of
      autografts, amniotic membranes and numerous synthetic/natural materials, have
      been developed. However, none of these strategies is completely satisfactory due
      to lack of goblet cell repopulation, poor mechanical properties or non
      standardized preparation procedure. Here, we cultured conjunctival epithelial
      cells on vitrified collagen membranes and developed a tissue equivalent for
      repairing damaged conjunctiva. Optimized vitrified collagen has superior
      mechanical and optical properties to previous biomaterials for ocular surface
      application, and its unique fibrillar structure significantly benefited
      conjunctival epithelial cell growth and the phenotypic development in vitro. In a
      rabbit model, vitrified collagen greatly promoted conjunctival regeneration with
      rapid re-epithelization, sufficient repopulation of goblet cells and minimized
      fibrosis and wound contracture, proved by gene expression analyses and
      histological staining. In conclusion, we have demonstrated the potential
      suitability of utilizing vitrified collagen-based tissue equivalent in ocular
      surface reconstruction. 

PMID- 24933513
TI  - Mimicking the extracellular matrix with functionalized, metal-assembled collagen
      peptide scaffolds.
AB  - Natural and synthetic three-dimensional (3-D) scaffolds that mimic the
      microenvironment of the extracellular matrix (ECM), with growth factor
      storage/release and the display of cell adhesion signals, offer numerous
      advantages for regenerative medicine and in vitro morphogenesis and oncogenesis
      modeling. Here we report the design of collagen mimetic peptides (CMPs) that
      assemble into a highly crosslinked 3-D matrix in response to metal ion stimuli,
      that may be functionalized with His-tagged cargoes, such as green fluorescent
      protein (GFP-His8) and human epidermal growth factor (hEGF-His6). The bound hEGF
      His6 was found to gradually release from the matrix in vitro and induce cell
      proliferation in the EGF-dependent cell line MCF10A. The additional incorporation
      of a cell adhesion sequence (RGDS) at the N-terminus of the CMP creates an
      environment that facilitated the organization of matrix-encapsulated MCF10A cells
      into spheroid structures, thus mimicking the ECM environment. 

PMID- 24933515
TI  - Coronary artery bypass graft: why is the saphenous vein prone to intimal
      hyperplasia?
AB  - Proliferation and migration of smooth muscle cells and the resultant intimal
      hyperplasia cause coronary artery bypass graft failure. Both internal mammary
      artery and saphenous vein are the most commonly used bypass conduits. Although an
      internal mammary artery graft is immune to restenosis, a saphenous vein graft is
      prone to develop restenosis. We found significantly higher activity of
      phosphatase and tensin homolog (PTEN) in the smooth muscle cells of the internal
      mammary artery than in the saphenous vein. In this article, we critically review
      the pathophysiology of vein-graft failure with detailed discussion of the
      involvement of various factors, including PTEN, matrix metalloproteinases, and
      tissue inhibitor of metalloproteinases, in uncontrolled proliferation and
      migration of smooth muscle cells towards the lumen, and invasion of the graft
      conduit. We identified potential target sites that could be useful in preventing
      and (or) reversing unwanted consequences following coronary artery bypass graft
      using saphenous vein. 

PMID- 24933516
TI  - Involuntary memories of emotional scenes: the effects of cue discriminability and
      emotion over time.
AB  - Involuntary episodic memories come to mind spontaneously--that is, with no
      preceding retrieval attempts. Such memories are frequent in daily life, in which
      they are predominantly positive and often triggered by situational features
      matching distinctive parts of the memory. However, individuals suffering from
      psychological disorders, such as posttraumatic stress disorder, have stressful,
      repetitive, and unwanted involuntary memories about negative events in their
      past. These unwanted recollections are disturbing and debilitating. Although such
      intrusive involuntary memories are observed across a range of clinical disorders,
      there is no broadly agreed upon explanation of their underlying mechanisms and no
      successful experimental simulations of their retrieval. In a series of
      experiments, we experimentally manipulated the activation of involuntary episodic
      memories for emotional and neutral scenes and predicted their activation on the
      basis of manipulations carried out at encoding and retrieval. Our findings
      suggest that the interplay between cue discriminability at the time of retrieval
      and emotional arousal at the time of encoding are crucial for explaining
      intrusive memories following negative events. While cue distinctiveness is
      important directly following encoding of the scenes, emotional intensity
      influences retrieval after delays of 24 hr and 1 week. Voluntary remembering
      follows the same pattern as involuntary remembering. Our results suggest an
      explanatory model of intrusive involuntary memory for emotional events in
      clinical disorders.

PMID- 24933514
TI  - Therapeutic potential of adipose-derived stromal cells in age-related
      osteoporosis.
AB  - Adipose-derived stromal cells (ASCs) are increasingly being used for orthopedic
      based tissue engineering approaches due to their ability to readily undergo
      osteogenic differentiation. In the present study, we used in vitro and in vivo
      approaches to evaluate the use of ASCs as a treatment strategy for age-related
      osteoporosis. Molecular, histological and micro-computed tomography (micro-CT)
      based approaches confirmed that ASCs isolated from 18-week-old osteoporotic
      senescence-accelerated mice (SAMP6) were capable of undergoing osteogenesis when
      cultured in either silk fibroin (SF) scaffolds or scaffold-free microtissues (ASC
      MT). A single intratibial injection of CM-Dil-labeled isogeneic ASCs or ASC-MT
      into SAMP6 recipients significantly improved trabecular bone quality after 6
      weeks in comparison to untreated contralateral bones, as determined by micro-CT.
      Injected ASCs could be observed in paraffin wax bone sections at 24 h and 6 weeks
      post treatment and induced a significant increase in several molecular markers of
      bone turnover. Furthermore, a significant improvement in the osteogenic potential
      of osteoporotic patient-derived human bone marrow stromal cells (BMSCs) was
      observed when differentiated in conditioned culture media harvested from
      osteoporotic patient-derived human ASCs. These findings therefore support the use
      of ASCs as an autologous cell-based approach for the treatment of osteoporosis. 

PMID- 24933517
TI  - Action video games do not improve the speed of information processing in simple
      perceptual tasks.
AB  - Previous research suggests that playing action video games improves performance
      on sensory, perceptual, and attentional tasks. For instance, Green, Pouget, and
      Bavelier (2010) used the diffusion model to decompose data from a motion
      detection task and estimate the contribution of several underlying psychological
      processes. Their analysis indicated that playing action video games leads to
      faster information processing, reduced response caution, and no difference in
      motor responding. Because perceptual learning is generally thought to be highly
      context-specific, this transfer from gaming is surprising and warrants
      corroborative evidence from a large-scale training study. We conducted 2
      experiments in which participants practiced either an action video game or a
      cognitive game in 5 separate, supervised sessions. Prior to each session and
      following the last session, participants performed a perceptual discrimination
      task. In the second experiment, we included a third condition in which no video
      games were played at all. Behavioral data and diffusion model parameters showed
      similar practice effects for the action gamers, the cognitive gamers, and the
      nongamers and suggest that, in contrast to earlier reports, playing action video
      games does not improve the speed of information processing in simple perceptual
      tasks.

PMID- 24933518
TI  - Bidirectional placental transfer of Bisphenol A and its main metabolite,
      Bisphenol A-Glucuronide, in the isolated perfused human placenta.
AB  - The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor
      interfering with developmental processes, raises the question of the risk for
      human health of BPA fetal exposure. In humans, highly variable BPA concentrations
      have been reported in the feto-placental compartment. However the human fetal
      exposure to BPA still remains unclear. The aim of the study was to characterize
      placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA
      G) using the non-recirculating dual human placental perfusion. This high
      placental bidirectional permeability to the lipid soluble BPA strongly suggests a
      transport by passive diffusion in both materno-to-fetal and feto-to-maternal
      direction, leading to a calculated ratio between fetal and maternal free BPA
      concentrations of about 1. In contrast, BPA-G has limited placental permeability,
      particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA
      conjugates could be explained mainly by its limited capacity to extrude BPA-G. 

PMID- 24933519
TI  - Fabrication of PLLA/beta-TCP nanocomposite scaffolds with hierarchical porosity
      for bone tissue engineering.
AB  - Polymer and ceramic composite scaffolds play a crucial role in bone tissue
      engineering. In an attempt to mimic the architecture of natural extracellular
      matrix (ECM), poly(l-lactic acid)/beta-tricalcium phosphate (PLLA/beta-TCP)
      nanocomposite scaffolds with a hierarchical pore structure were fabricated by
      combining thermal induced phase separation and salt leaching techniques. The
      nanocomposite scaffold consisted of a nanofibrous PLLA matrix with a highly
      interconnected, high porosity (>93%) hierarchical pore structure with pore
      diameters ranging from 500nm to 300MUm and a homogeneously distributed beta-TCP
      nanoparticle phase. The nanofibrous PLLA matrix had a fiber diameter of 70-300nm.
      The nanocomposite scaffolds possess three levels of hierarchical structure: (1)
      porosity; (2) nanofibrous PLLA struts comprising the pore walls; and (3) beta-TCP
      nanoparticle phase. The beta-TCP nanoparticle phase improved the mechanical
      properties and bioactivity of the PLLA matrix. The nanocomposite scaffolds
      supported MG-63 osteoblast proliferation, penetration, and ECM deposition,
      indicating the potential of PLLA/beta-TCP nanocomposite scaffolds with
      hierarchical porosity for bone tissue engineering applications. 

PMID- 24933520
TI  - A structural study on the protection of glycation of superoxide dismutase by
      thymoquinone.
AB  - Accumulation of advanced glycation end products (AGEs) in tissues and serum plays
      important roles in diabetes-associated complications. Therefore, the
      identification of antiglycating compounds is attracting considerable interest. In
      this study, the structural changes associated with the glycation of superoxide
      dismutase (SOD) and its protection by thymoquinone (TQ) have been investigated by
      biophysical techniques. Incubation of SOD with glucose, methylglyoxal (MG) or
      both at 37C resulted in progressive hyperchromicity at 280nm, intrinsic
      fluorescence quenching at 310nm, decrease in negative ellipticity at 208nm, AGE
      specific fluorescence enhancement in the wavelength range 400-480nm and
      Thioflavin T (ThT) fluorescence enhancement at 480nm (fibrillar state
      enhancement). Therefore, glycation by glucose or MG induced both tertiary and
      secondary structural changes in SOD and formation of AGEs and fibrils. The
      changes were more and faster with MG than with glucose since MG is a stronger
      glycating agent than glucose. TQ offered protection against glucose or MG-induced
      glycation of SOD as observed by a reduction in the structural changes, formation
      of AGEs and fibrils. Thus, TQ can be used for reducing diabetic complications
      many of which are due to protein glycation. 

PMID- 24933521
TI  - Properties of collagen gels cross-linked by N-hydroxysuccinimide activated adipic
      acid deriviate.
AB  - In order to improve the properties of collagen gel, N-hydroxysuccinimide
      activated adipic acid derivative (NHS-AA) was introduced into the formation of
      collagen fibrils. NHS-AA with different [NHS-AA]/[NH2] ratios (0.1-1.5,
      calculated by [ester group] of NHS-AA and [NH2] of lysine and hydroxylysine
      residues of collagen) was added after, simultaneously with or before the
      formation of collagen fibrils (abbreviated CAF, CSF and CBF, respectively) to
      obtain different collagen gels. With the same dose of NHS-AA, the cross-linking
      degree for CAF was lower than those for CSF and CBF. The formation of collagen
      fibrils was restrained by NHS-AA for CSF and CBF while that for CAF was
      unaffected. When the dose of NHS-AA increased from 0.1 to 1.5, the water contents
      of CSF and CBF increased while that of CAF had no obvious change. With lower dose
      of NHS-AA (0.1), CAF possessed higher value of G' (87.3Pa) and the best thermal
      stability (47.6 degrees C). As the ratio of [NHS-AA]/[NH2] increased to 1.5, CSF
      had the maximum value of G' (288.8Pa) and CAF had the best thermal stability
      (52.9 degrees C). These results showed collagen gels with different properties
      could be prepared by adding NHS-AA with different adding sequence and dose. 

PMID- 24933522
TI  - Regulating a benzodifuran single molecule redox switch via electrochemical gating
      and optimization of molecule/electrode coupling.
AB  - We report a novel strategy for the regulation of charge transport through single
      molecule junctions via the combination of external stimuli of electrode
      potential, internal modulation of molecular structures, and optimization of
      anchoring groups. We have designed redox-active benzodifuran (BDF) compounds as
      functional electronic units to fabricate metal-molecule-metal (m-M-m) junction
      devices by scanning tunneling microscopy (STM) and mechanically controllable
      break junctions (MCBJ). The conductance of thiol-terminated BDF can be tuned by
      changing the electrode potentials showing clearly an off/on/off single molecule
      redox switching effect. To optimize the response, a BDF molecule tailored with
      carbodithioate (-CS2(-)) anchoring groups was synthesized. Our studies show that
      replacement of thiol by carbodithioate not only enhances the junction conductance
      but also substantially improves the switching effect by enhancing the on/off
      ratio from 2.5 to 8. 

PMID- 24933523
TI  - Re: Role of diffusion-weighted MRI in differentiation of hepatic abscesses from
      non-infected fluid collections. A reply.

PMID- 24933524
TI  - Can diffusion-weighted imaging be used to differentiate brain abscess from other
      ring-enhancing brain lesions? A meta-analysis.
AB  - AIM: To explore the role of diffusion-weighted imaging (DWI) in the
      discrimination of brain abscess from other ring-enhancing brain lesions through
      meta-analysis. MATERIALS AND METHODS: The PUMBED, OVID, and China National
      Knowledge Infrastructure (CNKI) databases, from January 1995 to March 2013, were
      searched for studies evaluating the diagnostic performance of DWI in the
      discrimination of brain abscess lesions. Using the data collected, pooled
      sensitivities and specificities across studies were determined, positive and
      negative likelihood ratios (LR) were calculated, and summary receiver operating
      characteristic (SROC) curves were constructed. RESULTS: A total of 11 studies
      fulfilled all of the inclusion criteria and were considered for the analysis. The
      pooled sensitivity values and pooled specificity values including 95% confidence
      intervals (CI) were 0.95 (0.87-0.98) and 0.94 (0.88-0.97). The pooled positive LR
      (95% CI) was 4.13(2.55-6.7); the pooled negative LR (95% CI) was 0.01 (0-1.7);
      and the area under the curve of the symmetric SROC was 0.98. CONCLUSIONS: DWI has
      high sensitivity and specificity for the differentiation of brain abscess from
      other intracranial cystic mass lesions.

PMID- 24933525
TI  - How do health professionals support pregnant and young mothers in the community?
      A selective review of the research literature.
AB  - BACKGROUND: The cultural phenomenon of "teenage pregnancy and motherhood" has
      been socially constructed and (mis)represented in social and health care
      discourses for several decades. Despite a growing body of qualitative research
      that presents an alternative and positive view of young motherhood, there remains
      a significant gap between pregnant and young women's experience of young
      motherhood and current global health and social policy that directs service
      delivery and practice. AIM: This paper aims to heighten awareness of how a
      negative social construction of young motherhood influences global health and
      social policy that directs current community health models of practice and care
      for young mothers in the community. DISCUSSION: There is clear evidence on the
      vital role social support plays in young women's experience of pregnancy and
      motherhood, particularly in forming a positive motherhood identity. This
      discussion paper calls us to start open and honest dialogue on how we may begin
      to re-vision the 'deficit view' of young motherhood in order to address this
      contradiction between research evidence, policy discourse and current practice
      and service provision. Qualitative research that privileges young women's voices
      by considering the multidimensional experiences of young motherhood is an
      important step towards moving away from universally prescribed interventions to a
      non-standard approach that fosters relational and responsive relationships with
      young mothers that includes addressing the immediate needs of young mothers at
      the particular time.

PMID- 24933526
TI  - Women's expectations and experiences with labour pain in medical and midwifery
      models of birth in the United States.
AB  - BACKGROUND: This research focuses on how women understand and experience labour
      as related to two competing views of childbirth pain. The biomedical view is that
      labour pain is abnormal and anaesthesia/analgesia use is encouraged to relieve
      the pain. The midwifery view is that pain is a normal part of labour that should
      be worked with instead of against. AIMS: To determine differences in the
      preparation for and experiences with labour pain by women choosing midwives
      versus obstetricians. METHODS: Prenatal and postpartum in-depth semi-structured
      interviews were conducted with a convenience sample of 80 women in Florida
      (United States): 40 who had chosen an obstetrician and 40 who had chosen a
      licensed midwife as their birth practitioner. FINDINGS: Women in both groups were
      concerned with the pain of childbirth before and after their labour experiences.
      Women choosing midwives discussed preparing for pain through various non
      pharmaceutical coping methods, while women choosing physicians discussed
      pharmaceutical and non-pharmaceutical pain relief. CONCLUSIONS: Equal numbers of
      women expressed concerns with childbirth pain during the prenatal interviews,
      while more women choosing doctors spoke about pain after their births. Women had
      negative experiences when their planned pain relief method, either natural or
      medical, did not occur. The quandary facing women when it comes to labour pain
      relief is not choosing what they desire, but rather preparing themselves for the
      possibility that they may have to accept alternatives to their original
      preferences.

PMID- 24933527
TI  - Finding an emotional face in a crowd: emotional and perceptual stimulus factors
      influence visual search efficiency.
AB  - In this article, we examine how emotional and perceptual stimulus factors
      influence visual search efficiency. In an initial task, we run a visual search
      task, using a large number of target/distractor emotion combinations. In two
      subsequent tasks, we then assess measures of perceptual (rated and computational
      distances) and emotional (rated valence, arousal and potency) stimulus
      properties. In a series of regression analyses, we then explore the degree to
      which target salience (the size of target/distractor dissimilarities) on these
      emotional and perceptual measures predict the outcome on search efficiency
      measures (response times and accuracy) from the visual search task. The results
      show that both emotional and perceptual stimulus salience contribute to visual
      search efficiency. The results show that among the emotional measures, salience
      on arousal measures was more influential than valence salience. The importance of
      the arousal factor may be a contributing factor to contradictory history of
      results within this field. 

PMID- 24933529
TI  - Engineering bacteria to form a biofilm and induce clumping in Caenorhabditis
      elegans.
AB  - Bacteria are needed for a vast range of biotechnological processes, which they
      carry out either as pure cultures or in association with other bacteria and/or
      fungi. The potential of bacteria as biofactories is hampered, though, by their
      limited mobility in solid or semisolid media such as agricultural or domestic
      waste. This work represents an attempt toward overcoming this limitation by
      associating bacterial biotechnological properties with the transport ability of
      the nematode Caenorhabditis elegans. We report here biofilm formation on C.
      elegans by engineered Escherichia coli expressing a Xhenorhabdus nematophila
      adhesion operon and induction of nematode social feeding behavior (clumping)
      through an E. coli-mediated iRNA blocking on the expression of FLP-21, a
      neuropeptide involved in worm solitary behavior. 

PMID- 24933528
TI  - Spatial variations in Achilles tendon shear wave speed.
AB  - Supersonic shear imaging (SSI) is an ultrasound imaging modality that can provide
      insight into tissue mechanics by measuring shear wave propagation speed, a
      property that depends on tissue elasticity. SSI has previously been used to
      characterize the increase in Achilles tendon shear wave speed that occurs with
      loading, an effect attributable to the strain-stiffening behavior of the tissue.
      However, little is known about how shear wave speed varies spatially, which is
      important, given the anatomical variation that occurs between the calcaneus
      insertion and the gastrocnemius musculotendon junction. The purpose of this study
      was to investigate spatial variations in shear wave speed along medial and
      lateral paths of the Achilles tendon for three different ankle postures: resting
      ankle angle (R, i.e. neutral), plantarflexed (P; R - 15 degrees ), and
      dorsiflexed (D; R+15 degrees ). We observed significant spatial and posture
      variations in tendon shear wave speed in ten healthy young adults. Shear wave
      speeds in the Achilles free tendon averaged 12 +/- 1.2m/s in a resting position,
      but decreased to 7.2 +/- 1.8m/s with passive plantarflexion. Distal tendon shear
      wave speeds often reached the maximum tracking limit (16.3m/s) of the system when
      the ankle was in the passively dorsiflexed posture (+15 degrees  from R). At a
      fixed posture, shear wave speeds decreased significantly from the free tendon to
      the gastrocnemius musculotendon junction, with slightly higher speeds measured on
      the medial side than on the lateral side. Shear wave speeds were only weakly
      correlated with the thickness and depth of the tendon, suggesting that the distal
      to-proximal variations may reflect greater compliance in the aponeurosis relative
      to the free tendon. The results highlight the importance of considering both limb
      posture and transducer positioning when using SSI for biomechanical and clinical
      assessments of the Achilles tendon.

PMID- 24933530
TI  - Pharmacokinetics and tissue distribution of ginsenoside Rh2 and Rg3 epimers after
      oral administration of BST204, a purified ginseng dry extract, in rats.
AB  - 1. BST204, a purified ginseng dry extract containing a high concentration of
      racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in
      cancer patients in Korea. This study investigates the pharmacokinetics and tissue
      distribution of BST204 in rats. 2. After oral administration of BST204, only the
      S epimers, S-Rh2 and S-Rg3, could be determined in rat plasma. The poor
      absorption of the R-epimers, R-Rh2 and R-Rg3, may be attributed to lower membrane
      permeability and extensive intestinal oxygenation and/or deglycosylation into
      metabolites. The AUC and Cmax values of both S-Rh2 and S-Rg3 after BST204 oral
      administration were proportional to the administered BST204 doses ranged from 400
      mg/kg to 2000 mg/kg, which suggested linear pharmacokinetic properties. 3. There
      were no statistically significant differences in the pharmacokinetics of S-Rh2
      and S-Rg3 after oral administration of pure S-Rh2 (31.5 mg/kg) and S-Rg3 (68
      mg/kg) compared with oral administration of BST204, 1000 mg/kg. These indicated
      that the presence of other components of BST204 extract did not influence the
      pharmacokinetic behavior of S-Rh2 and S-Rg3. 4. After oral dosing of BST204, S
      Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in
      rats. 5. Our finding may help to understand pharmacokinetic characteristics of S
      Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in
      clinical application of BST204.

PMID- 24933531
TI  - Strain- and context-dependent effects of the anandamide hydrolysis inhibitor
      URB597 on social behavior in rats.
AB  - Genetic and environmental factors play an important role in the cannabinoid
      modulation of motivation and emotion. Therefore, the aim of the present study was
      to test whether anandamide modulation of social behavior is strain- and context
      dependent. We tested the effects of the anandamide hydrolysis inhibitor URB597 on
      social behavior and 50-kHz ultrasonic vocalizations (USVs) in adolescent and
      adult Wistar and Sprague-Dawley rats tested in different emotionally arousing
      conditions (familiarity/unfamiliarity to the test cage, low/high light). Under
      all experimental conditions, adolescent and adult Sprague-Dawley rats displayed
      higher levels of social behavior and emitted more 50-kHz USVs than Wistar rats.
      URB597 enhanced social play behavior in adolescent Wistar rats under all
      experimental conditions. However, URB597 only increased social interaction in
      adult Wistar rats under unfamiliar/high light conditions. URB597 did not affect
      adolescent social play behavior and adult social interaction in Sprague-Dawley
      rats under any experimental condition. Moreover, URB597 increased the USVs
      emitted during social interaction by adolescent Wistar and adult Sprague-Dawley
      rats tested under familiar/high light and unfamiliar/high light, respectively.
      These results show that anandamide has distinct roles in adolescent and adult
      social behaviors. Anandamide modulation of adolescent social play behavior is
      strain- but not context-dependent. Conversely, anandamide modulation of adult
      social behavior and USV emission depends upon both strain and experimental
      context. Furthermore, these results confirm that profound behavioral differences
      exist between Wistar and Sprague-Dawley rats, which may explain the sometimes
      contradictory effects of cannabinoid drugs on emotionality in different strains
      of rodents. 

PMID- 24933532
TI  - Hallucinogen persisting perception disorder and the serotonergic system: a
      comprehensive review including new MDMA-related clinical cases.
AB  - Hallucinogen persisting perception disorder (HPPD) is a drug-induced condition
      associated with inaccurate visual representations. Since the underlying
      mechanism(s) are largely unknown, this review aims to uncover aspects underlying
      its etiology. Available evidence on HPPD and drug-related altered visual
      processing was reviewed and the majority of HPPD cases were attributed to drugs
      with agonistic effects on serotonergic 5-HT2A receptors. Moreover, we present 31
      new HPPD cases that link HPPD to the use of ecstasy (MDMA), which is known to
      reverse serotonin reuptake and acts as agonist on 5-HT2A receptors. The available
      evidence suggests that HPPD symptoms may be a result from a misbalance of
      inhibitory-excitatory activity in low-level visual processing and GABA-releasing
      inhibitory interneurons may be involved. However, high co-morbidities with
      anxiety, attention problems and derealization symptoms add complexity to the
      etiology of HPPD. Also, other perceptual disorders that show similarity to HPPD
      cannot be ruled out in presentations to clinical treatment. Taken together,
      evidence is still sparse, though low-level visual processing may play an
      important role. A novel finding of this review study, evidenced by our new cases,
      is that ecstasy (MDMA) use may also induce symptoms of HPPD.

PMID- 24933533
TI  - Patient satisfaction with community pharmacy: comparing urban and suburban chain
      pharmacy populations.
AB  - BACKGROUND: Patient satisfaction with pharmaceutical care can be a strong
      predictor of medication and other health-related outcomes. Less understood is the
      role that location of pharmacies in urban or suburban environments plays in
      patient satisfaction with pharmacy and pharmacist services. OBJECTIVES: The
      purpose of this study was to serve as a pilot examining urban and suburban
      community pharmacy populations for similarities and differences in patient
      satisfaction. METHODS: Community pharmacy patients were asked to self-administer
      a 30-question patient satisfaction survey. Fifteen questions addressed their
      relationship with the pharmacist, 10 questions addressed satisfaction and
      accessibility of the pharmacy, and five questions addressed financial concerns.
      Five urban and five suburban pharmacies agreed to participate. Data analysis
      included descriptive statistics and chi-square analysis. RESULTS: Most patients
      reported high levels of satisfaction. Satisfaction with pharmacist relationship
      and service was 70% or higher with no significant differences between locations.
      There were significant differences between the urban and suburban patients
      regarding accessibility of pharmacy services, customer service and some
      patient/pharmacist trust issues. CONCLUSIONS: The significant differences between
      patient satisfaction in the suburban and urban populations warrant a larger study
      with more community pharmacies in other urban, suburban and rural locations to
      better understand and validate study findings.

PMID- 24933534
TI  - Motor imagery modulation of postural sway is accompanied by changes in the EMG
      COP association.
AB  - Motor imagery (MI) performed in an upright stance promotes increases in postural
      sway without changes in usual amplitude measures of calf muscle EMG. However,
      postural muscle activity can also be determined from the temporal association
      between EMG and center of pressure (COP) displacements. In this study we
      investigated whether the MI modulation of postural sway is accompanied by changes
      in EMG-COP association. Surface EMG from the lateral gastrocnemius (LG) muscle
      and COP coordinates were collected from 12 subjects while they imagined
      themselves performing a rising on tiptoes movement via kinesthetic or visual
      imagery. As a control condition subjects were requested to imagine singing a
      song. The standard deviation of the forward-backward COP sway and the coefficient
      of variation of the EMG were calculated and compared across tasks. The degree of
      association between COP sways and LG activity was evaluated through a cross
      correlation function. Kinesthetic imagery promoted a larger COP displacement than
      both visual and control imagery (p<0.02). No difference in EMG amplitude was
      observed across imagery tasks (p=0.08). Crucially, we found a stronger EMG-COP
      association during kinesthetic imagery compared to control imagery (p=0.02),
      whereas the EMG-COP association in visual imagery was not different from that
      observed during kinesthetic or control imagery (p>0.19). In conclusion,
      kinesthetic imagery resulted in a higher EMG-COP temporal association. Subliminal
      fringe mechanisms may account for the imagery effects on muscle activity and
      postural sway during upright stance. 

PMID- 24933535
TI  - Hexamethonium-induced augmentation of the electrical twitch response in the
      guinea-pig ileum longitudinal muscle-myenteric plexus strip.
AB  - Longitudinal muscle-myenteric plexus strips of the guinea-pig ileum were used to
      investigate the nature of the hexamethonium-induced augmentation of the twitch
      response. All preparations were set up in Tyrode solution and intermittent
      longitudinal twitch contractions were evoked by single pulse electrical field
      stimulation. Hexamethonium, a blocker of nicotinic ganglionic transmission, at
      300 MUmol/l and 1 mmol/l augmented the twitch contractions by 21% and 35%,
      respectively. First we tested for a possible nicotinic drive onto an inhibitory
      neuronal component to the longitudinal smooth muscle cells. However, guanethidine
      (5 MUmol/l), naloxone (1 MUmol/l), or l-NAME (300 MUmol/l) were without effect on
      the hexamethonium-induced augmentation. The P2 purinoceptor antagonist
      pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), 25-100 MUmol/l,
      without altering the control twitch responses, dose-dependently reduced the
      hexamethonium-induced augmentation; at 100 MUmol/l a statistically significantly
      inhibition was observed. Based on these functional experiments we found no
      evidence that blocking nicotinic transmission removed a tonic adrenergic,
      opioidergic or nitrergic inhibitory input to the longitudinal muscle. However, we
      provide evidence for a hexamethonium-induced augmentation of the P2 purinergic
      input to cholinergic motoneurons of the guinea-pig ileum longitudinal muscle. The
      P2-nicotinic receptor interaction presents a novel modulatory mechanism to
      cholinergic myenteric motor neurons.

PMID- 24933537
TI  - Does overestimation of an object's mass during arm-raising modify postural
      adjustments?
AB  - By using a dummy weight during an arm-raising movement, we sought to determine
      whether (i) postural adjustments are modified and (ii) the required focal
      movement can be performed adequately. Standing on a force platform, 30 healthy
      young adults performed voluntary, arm-raising movements with cube-shaped boxes: a
      small 1 kg box, a large 4 kg box and a large 1 kg box (i.e. the dummy weight,
      which looked as if it weighed 4 kg). Postural adjustments were quantified in
      terms of the latency, intensity and duration of the positive phase of the
      vertical torque (Tz) and displacements of the center of pressure. Lifting the
      dummy and lifting the small 1 kg box were associated with similar arm velocity
      curves. The characteristics of the positive Tz phase for the dummy box were
      intermediate between those observed for the small 1 kg box and the large 4 kg
      box. There were no differences between the three box-lifting conditions in terms
      of the latency and duration of Tz. We conclude that overestimation of the dummy's
      mass was rapidly corrected by a feedback mechanism. Postural control was modified
      online as soon as the dummy's true weight was perceived, which therefore enabled
      the maintenance of balance and adequate execution of the voluntary (focal)
      movement.

PMID- 24933536
TI  - Serial processing in primary and secondary somatosensory cortex: A DCM analysis
      of human fMRI data in response to innocuous and noxious electrical stimulation.
AB  - The anatomy of the somatosensory system allows both serial and parallel
      information flow but the conditions involving each mode of processing is a matter
      of debate. In this functional magnetic resonance imaging (fMRI) study, cutaneous
      electrical stimulation was applied to human volunteers at three intensities (low
      innocuous, moderate-noxious and high-noxious) to investigate interactions between
      contralateral primary and secondary somatosensory cortices (S1c and S2c), and
      between contralateral and ipsilateral S2 (S2c and S2i), using dynamic causal
      modeling (DCM). Our results are consistent with serial processing with a key role
      of the direct input to S1c for all three intensity levels. The more intense
      stimulus also induced significantly more interactions between S2i and S2c,
      consistent with an increase in inter-hemispheric integration associated with the
      additional recruitment of nociceptive inputs. However, stronger pain reports were
      also associated with reduced information flow from S1c to S2c at both the
      moderate (r=-0.81, p=0.004) and the high stimulation level (r=-0.63, p=0.037).
      These findings suggest that the connectivity pattern driven by innocuous inputs
      is modified by the additional activation of nociceptive afferents. 

PMID- 24933539
TI  - Extraction of practice-dependent and practice-independent finger movement
      patterns.
AB  - Extensive motor practice can reorganize movements of a redundant number of
      degrees of freedom (DOFs). Using principal component (PC) analysis, the present
      study characterized the movement reorganization of the hand that possesses a
      large number of DOFs during a course of practice. Five musically naive
      individuals practiced to play a short sequence of melody with the left hand for
      four successive days, and their hand kinematics was measured using a motion
      capture system. The PC analysis of the hand joint kinematics identified two
      distinct patterns of movement, which accounted for more than 80% of the total
      variance of movements. The second PC but not the first PC changed through
      practice. A correlation analysis demonstrated that the PC sensitive to the
      practice was characterized by coupled movements across fingers in the same
      direction. A regression analysis identified a decrease in the contribution of
      this PC to the hand movement organization through practice, which indicates a
      reduction of the movement covariation across fingers and thus an enhancement of
      the individuated finger movements. The results implicate potential of PC analysis
      to extract practice-invariant and practice-dependent movement patterns
      distinctively in complex hand motor behaviors. 

PMID- 24933538
TI  - Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via
      inhibition of inflammatory responses.
AB  - Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's
      disease (AD), but the underlying mechanisms remain unclear. In this study, Morris
      water maze test, ELISA and electrophysiological methods were used to examine the
      role and underling mechanisms of rosiglitazone on Abeta42 oligomer-induced memory
      impairments. We found that rosiglitazone attenuated Abeta42 oligomer-induced
      memory impairments in rats in a dose-dependent manner. The levels of inflammatory
      cytokines interleukin-1 beta (IL-1beta) and interferon gamma (IFNgamma) were
      significantly increased 7 days after injection of Abeta42 oligomers into the rat
      hippocampus. Inhibition of microglia activation prevented Abeta42 oligomer
      induced increases in IL-1beta and IFNgamma levels. Rosiglitazone completely
      prevented the increase in the levels of IL-1beta and IFNgamma induced by Abeta42
      oligomers. Treatment of hippocampal slices with the inflammatory cytokine IL
      1beta or IFNgamma significantly inhibited the production of long-term
      potentiation (LTP) in the dentate gyrus. Rosiglitazone prevented the inhibitory
      effects of inflammatory cytokines on LTP. Thus, inhibition of inflammatory
      responses may be part of the mechanisms of action of rosiglitazone on preventing
      memory deficits induced by Abeta42 oligmers. 

PMID- 24933540
TI  - Functional assessment in older adults: should we use timed up and go or gait
      speed test?
AB  - In order to assess functional skills of older adults, both timed up and go (TUG)
      test and gait speed (GS) test are well validated concerning their predictive
      capacities. However, the question remains unclear which one of these tests
      represents better the whole physical performance of older adults. The aim of this
      study is to determine the more representative test, between TUG and GS, of the
      whole motor control quality. To study links between locomotion capacities and arm
      function, we measured, in a population of frail aged patients, the locomotion
      tests and the mean arm maximal velocity developed during a speed-accuracy trade
      off. This arm movement consisted in reaching the hand toward a target in a
      virtual game scene. We plotted the different couples of variables obtained on
      graphs, and calculate Pearson correlation coefficients between each couple. The
      Pearson correlation between GS and hand maximal velocity was significant
      (r=0.495; p=0.046). Interestingly, we found a non significant Pearson correlation
      between timed up and go score (TUG) and hand maximal velocity (r=-0.139;
      p=0.243). Our results suggest that GS score is more representative of the whole
      motor ability of frail patients than the TUG. We propose that the relative
      complexity of the TUG motor sequence could be involved in this difference. For a
      few patients with motor automatisms deficiencies, this motor sequence complexity
      could leads to a dual task perturbation. In this way, we conclude that GS should
      be preferred over the TUG with older adults. 

PMID- 24933541
TI  - Giving credit where it's due.

PMID- 24933542
TI  - Going gender-neutral with the HPV vaccine.

PMID- 24933543
TI  - Medication errors in a public hospital in Brazil.
AB  - This article describes the analysis of the frequency, type and risk factors
      relating to errors in the preparation and administration of medications in
      patients admitted to a public hospital in Brasilia Federal District, Brazil,
      which serves a population of approximately 500,000 inhabitants. Patients are
      commonly affected and harmed by medication errors, almost half of which are
      preventable. This is a cross-sectional, descriptive and exploratory study
      conducted in a clinical medicine unit. Direct observations were made by eight
      nurse technicians. The type of error, the type of drug involved and associated
      risk factors were analysed. Relationships between the occurrence of errors and
      risk factors were studied with logistic regression models. Of the 484 observed
      doses, 69.5% errors occurred during drug administration, 69.6% during the
      preparation stage, 48.6% were timing errors, 1.7% were dose-related errors and
      9.5% were errors of omission. More than one error was detected in 34.5% of
      occasions. Unlabelled drugs increased the risk of timing errors by a factor of
      13.72. Interruptions in preparation increased the risk of errors by a factor of
      3.75. Caring for a larger number of patients (8-9) increased the risk of timing
      errors by a factor of 8.27. The research shows the need to manage the risk of
      medication errors in their real-life contexts by interposing safety barriers
      between the hazards and potential errors. 

PMID- 24933544
TI  - The return of autonomy in nursing: a way forward.

PMID- 24933545
TI  - Valid informed consent in research: an introduction.

PMID- 24933546
TI  - Coaching to promote professional development in nursing practice.
AB  - This article presents coaching, which facilitates the highest form of learning,
      as a potential strategy for promoting professional development in nursing. In
      doing so, it sets out what coaching is and highlights its benefits in terms of
      team building, adaptation to changes, career planning and professional
      development. Having established the rudiments of coaching and identifying its
      qualities, the article then sets out strategies of coaching using three models:
      the 3-D Technique Model, The Practice Spiral Model and The Grow Model. Three case
      histories are presented to explain how these models could be used to implement
      coaching and personal learning plans (PLP). Directions are provided where
      training for coaching is available. It is concluded that coaching can be a
      powerful tool in enhancing nurses' and other health professionals' ability to
      contribute to the success of healthcare organisations. 

PMID- 24933547
TI  - Effectiveness of alcohol brief interventions in general practice.
AB  - Harmful levels of alcohol consumption are a longstanding but continually growing
      health concern affecting individuals, and consequently populations. Through
      personalised advice, alcohol brief interventions (ABIs) target drinking habits,
      which are deemed damaging to health. They are not targeted at dependent drinkers
      for whom a more intensive and specialist service would be better suited. In
      response to recent shifts in public-health strategy away from ABIs, and the
      publication of new trials into their effectiveness, this article evaluates the
      value of ABIs through the review of eleven relevant studies. Findings suggest
      that hazardous drinkers did reduce their drinking patterns following ABI, but not
      more so than control participants who were given standard treatment. The
      evolution of standard treatment to include thorough screening, non-personalised
      advice and sometimes literature on alcohol intake delivers an intervention, that
      is effective in reducing drinking. Therefore, future research and practice should
      focus on screening methods and quality of standard care rather than on brief
      interventions. 

PMID- 24933548
TI  - Fingolimod for multiple sclerosis: a review for the specialist nurse.
AB  - The availability of treatments for multiple sclerosis (MS) has increased
      substantially over the past decade. Once-daily fingolimod 0.5 mg capsules
      (Gilenya, Novartis Pharma) were approved in the European Union in March 2011 as
      the first oral disease-modifying therapy for patients with relapsing MS. This
      review summarises the efficacy and safety of fingolimod, and discusses practical
      considerations for MS specialist nurses. Fingolimod has demonstrated efficacy in
      the treatment of relapsing-remitting MS, as assessed by relapse measures,
      inflammatory disease activity and brain volume loss. Evaluation of its safety
      profile suggests a need for monitoring procedures for specific adverse events,
      including transient, mostly asymptomatic, reductions in heart rate, blood
      pressure increases, macular oedema and liver enzyme elevations. The MS nurse is
      likely to be involved in monitoring treatment initiation, providing support in
      the case of adverse events and promoting patient adherence to the prescribed
      treatment regimen. 

PMID- 24933549
TI  - Swab and instrument count practice: ways to enhance patient safety.
AB  - This article presents the results of an audit of swab and instrument count
      practices in the operating department of a large hospital NHS Trust in South East
      England. A literature review of the subject is presented followed by the
      methodology used including questionnaires and observation of practice. Findings
      are discussed in terms of compliance with the department's swab and instrument
      count policy and observed practice mapped against the recommendations for best
      practice in the literature. The findings show that audit of practice is still
      treated with suspicion by many and that a number of practices of scrub and
      circulating personnel in operating theatres need to be improved. Recommendations
      are made related to improving staff development in the department and introducing
      clinical supervision as one way to provide support for colleagues to reflect on
      their practice and change to more evidence-based practices in the operating
      department. 

PMID- 24933551
TI  - Reflection: from staff nurse to nurse consultant. Part 9: Portfolios and
      reflection.

PMID- 24933550
TI  - A 'new wave' of CQC inspections.

PMID- 24933552
TI  - Improving services for disabled children and their families.

PMID- 24933553
TI  - Why asthma is killing and patient care is falling short.

PMID- 24933554
TI  - Theory into practice (sometimes doesn't go).

PMID- 24933555
TI  - Dementia care: knowledge is power.

PMID- 24933556
TI  - AC electric field induced dipole-based on-chip 3D cell rotation.
AB  - The precise rotation of suspended cells is one of the many fundamental
      manipulations used in a wide range of biotechnological applications such as cell
      injection and enucleation in nuclear transfer (NT) cloning. Noticeably scarce
      among the existing rotation techniques is the three-dimensional (3D) rotation of
      cells on a single chip. Here we present an alternating current (ac) induced
      electric field-based biochip platform, which has an open-top sub-mm square
      chamber enclosed by four sidewall electrodes and two bottom electrodes, to
      achieve rotation about the two axes, thus 3D cell rotation. By applying an ac
      potential to the four sidewall electrodes, an in-plane (yaw) rotating electric
      field is generated and in-plane rotation is achieved. Similarly, by applying an
      ac potential to two opposite sidewall electrodes and the two bottom electrodes,
      an out-of-plane (pitch) rotating electric field is generated and rolling rotation
      is achieved. As a prompt proof-of-concept, bottom electrodes were constructed
      with transparent indium tin oxide (ITO) using the standard lift-off process and
      the sidewall electrodes were constructed using a low-cost micro-milling process
      and then assembled to form the chip. Through experiments, we demonstrate rotation
      of bovine oocytes of ~120 MUm diameter about two axes, with the capability of
      controlling the rotation direction and the rate for each axis through control of
      the ac potential amplitude, frequency, and phase shift, and cell medium
      conductivity. The maximum observed rotation rate reached nearly 140 degrees  s-1,
      while a consistent rotation rate reached up to 40 degrees  s-1. Rotation rate
      spectra for zona pellucida-intact and zona pellucida-free oocytes were further
      compared and found to have no effective difference. This simple, transparent,
      cheap-to-manufacture, and open-top platform allows additional functional modules
      to be integrated to become a more powerful cell manipulation system.

PMID- 24933557
TI  - Hexa- and trinuclear organoantimony oxo clusters stabilized by organosilanols.
AB  - Reactions of Ph2SbCl3 with RSi(OH)3 [where R = tert-Bu, cyclo-C6H11] and
      Ph2Si(OH)2 in toluene in the presence of triethylamine as a base were performed.
      Single-crystal X-ray structural elucidation of the products revealed the
      formation of hexanuclear antimony(V) and mixed-valent antimony (III/V) oxo
      hydroxo clusters built up of an incomplete cubane subunit. Interestingly, in all
      the reactions, at least one Sb-C bond cleavage has been observed, leading to the
      formation of novel cluster assemblies [(Ph2Sb)4(PhSb)2(C4H9SiO3)2(O)6(OH)2] (1),
      [(Ph2Sb)4(PhSb)2(C6H11SiO3)2(O)6(OH)2] (2), [(Ph2Sb)(PhSb)2(Ph2SiO2)2(O)3(OH)2](
      )Et3NH(+) (3), and [(Ph2Sb)4(Sb)2(Ph2SiO2)2(O)6(OH)2] (4), respectively. 

PMID- 24933558
TI  - Introduction: gene and cell therapy projects of the seventh framework program.

PMID- 24933559
TI  - Persisting transgenesis (PERSIST).

PMID- 24933560
TI  - Advanced cell-based therapies for the treatment of primary immunodeficiency (Cell
      PID).

PMID- 24933561
TI  - Nonhuman adenovirus vectors for gene transfer to the brain (BrainCAV).

PMID- 24933562
TI  - Biodegradable magnetic stent for coronary artery luminal regeneration
      (Biomagscar).

PMID- 24933563
TI  - Augmenting PBGD expression in the liver as a novel gene therapy for acute
      intermittent porphyria (AIPgene).

PMID- 24933564
TI  - Gene-activated matrices for bone and cartilage regeneration in arthritis (GAMBA).

PMID- 24933565
TI  - Phase I/II ex vivo gene therapy clinical trial for recessive dystrophic
      epidermolysis bullosa using skin equivalent grafts genetically corrected with a
      COL7A1-encoding SIN retroviral vector (GENEGRAFT).

PMID- 24933566
TI  - Therapeutic challenge in leukodystrophies: translational and ethical research
      toward clinical trials (LeukoTreat).

PMID- 24933567
TI  - Optimization of stem cell therapy for clinical trials of degenerative skin and
      muscle diseases (OptiStem).

PMID- 24933568
TI  - Fighting blindness of Usher syndrome: diagnosis, pathogenesis, and retinal
      treatment (TreatRetUsher) (TREATRUSH).

PMID- 24933570
TI  - Congratulations to the winners of the 12 Pioneer Awards for seminal work in gene
      and cell therapy.

PMID- 24933569
TI  - Pulsed versus continuous application of the prodrug 5-fluorocytosine to enhance
      the oncolytic effectiveness of a measles vaccine virus armed with a suicide gene.
AB  - Abstract Oncolytic virotherapy with measles vaccine virus (MeV) already has been
      demonstrated to be safe. However, early clinical results pointed out the
      necessity for an enhancement of oncolytic effectiveness of MeV-based
      virotherapeutics. In our work, we are developing an armed measles vaccine virus
      (MeV-SCD) encoding a suicide fusion gene of yeast cytosine deaminase/uracil
      phosphoribosyltransferase, converting the nontoxic prodrug 5-fluorocytosine (5
      FC) to the chemotherapeutic drug 5-fluorouracil (5-FU). To preclinically
      investigate what an optimal prodrug-assisted therapeutic regimen might look like,
      we added 5-FC at various time points after infection with MeV-SCD and either let
      the prodrug remain in the tumor cell culture medium continuously for various time
      periods ("continuous" 5-FC application) or applied it only temporarily for
      defined shorter periods of time ("pulsed" 5-FC application); we also varied the
      time point at which 5-FC was added after infection with MeV-SCD. As a result,
      addition of the prodrug at early times postinfection (e.g., at 3 hr
      postinfection) was found to be inferior concerning the overall oncolytic
      effectiveness when compared with addition of 5-FC at later time points (e.g., at
      24 hr postinfection). Next, oncolytic effectiveness was found to correlate
      positively with the overall duration of incubation of MeV-infected tumor cells
      with 5-FC. Of note, this was true despite our finding that addition of the
      prodrug could also exert an inhibitory effect on the generation of infectious
      progeny viral particles, that is, on virus replication. These findings should be
      helpful for the rational design of further trials (preclinical, clinical) using
      suicide gene armed virotherapeutics, such as MeV-SCD. 

PMID- 24933571
TI  - Powerhouse down: Complex II dissociation in the respiratory chain.
AB  - Complex II of the respiratory chain (RC) recently emerged as a prominent
      regulator of cell death. In both cancer cells as well as neurodegenerative
      diseases, mutations in subunits have been found along with other genetic
      alterations indirectly affecting this complex. Anticancer compounds were
      developed that target complex II and cause cell death in a tumor-specific way.
      Our mechanistic understanding of how complex II is activated for cell death
      induction has recently been made clearer in recent studies, the results of which
      are covered in this review. This protein assembly is specifically activated for
      cell death via the dissociation of its SDHA and SDHB subunits from the membrane
      anchoring proteins through pH change or mitochondrial Ca(2+) influx. The SDH
      activity contained in the SDHA/SDHB subcomplex remains intact and then generates,
      in an uncontrolled fashion, excessive amounts of reactive oxygen species (ROS)
      for cell death. Future studies on this mitochondrial complex will further
      elucidate it as a target for cancer treatments and reveal its role as a nexus for
      many diverse stimuli in cell death signaling. 

PMID- 24933572
TI  - Forced distribution rating systems: when does "rank and yank" lead to adverse
      impact?
AB  - Despite widespread use of forced distribution rating systems (FDRSs), the
      potential for this performance appraisal method to lead to adverse impact (AI) in
      a layoff context has yet to be examined empirically. Thus, the current study uses
      a Monte Carlo simulation to examine the likelihood of encountering AI violations
      when an FDRS is used in the context of layoffs. The primary research questions
      included an examination of how AI violations change depending on the definition
      of the employment action (i.e., retention vs. layoff), the length of the repeated
      layoffs, and whether or not laid off employees are replaced each year. The
      current study also examined the impact of the size of the organization, the
      percentage of the workforce laid off, and the type of AI calculation method used
      on the likelihood of AI violations. Results suggest that defining the employment
      action as layoffs (rather than as retentions) may result in a greater likelihood
      of AI violations, and AI violations are likely to peak in the 1st year of use.
      Further, replacing laid off employees may result in higher levels of AI over time
      as compared with not replacing layoffs. Additionally, the greatest risk for AI
      occurs when the organization size is large (i.e., N = 10,000) and when certain AI
      calculation methods are used. Results are discussed in terms of their practical
      and legal implications for organizations.

PMID- 24933573
TI  - Towards exhaustive and automated high-throughput screening for crystalline
      polymorphs.
AB  - Methods capable of exhaustively screening for crystal polymorphism remain an
      elusive goal in solid-state chemistry. Particularly promising among the new
      generation of approaches is polymer-induced heteronucleation (PIHn), a tool
      utilizing hundreds of unique polymers for granting kinetic access to polymorphs.
      Here PIHn is redeployed in a high density format in which 288 distinct polymers,
      each acting as a heteronucleant, are arrayed on one substrate. This format allows
      determining the outcome of thousands of crystallizations in an automated fashion
      with only a few milligrams of sample. This technology enables the study of a
      broader range of targets, including preclinical candidates, facilitating
      determination of polymorphism propensity much earlier in the drug development
      process. Here the efficacy of this approach is demonstrated using four
      pharmaceutically relevant compounds: acetaminophen, tolfenamic acid, ROY, and
      curcumin. 

PMID- 24933574
TI  - Demographic characteristics and prognostic indicators of childhood burn in a
      developing country.
AB  - Children constitute a significant proportion of burn victims in most studies from
      the developing countries. While there has been a progressive improvement in the
      outcome from childhood burn in many developed nations, the morbidity and
      mortality remains high in many low and middle income countries. The aim of our
      study is to evaluate the demographic characteristics and prognostic indicators of
      childhood burn in a major referral teaching hospital in a developing country. A
      review of the records of 638 patients with acute burns managed over a 10-year
      period from January 2001 to December 2010 at the University College Hospital,
      Ibadan Nigeria was done. The clinical and epidemiological data were retrieved
      from computerized data base using the ISBI proforma. Information obtained
      includes Biodata, Etiology, location, TBSA, presence of Inhalation injury and the
      treatment outcome. Data of patients aged 16 years and below were analyzed using
      the SPSS version 16. The main outcome measure was the patient's survival. 289
      children representing 45.3% of the total number of burn patients were managed
      over the period. The M:F ratio was 1.1:1. The median age of the cohort was 4.0
      years while the median TBSA was 21.0%. Non-intentional causes were responsible
      for 89.6% cases. Most of the injuries (88.6%) occurred at home. Eighty-three
      patients had inhalation injury out of which 57 (68.7%) deaths were recorded. The
      overall mortality rate in the cohort was 39.5% with an LA50 of burn size of 45%.
      The TBSA was also found to be a determinant of outcome. Majority of childhood
      burns are from preventable causes with attendant dismal mortality figures.
      Effective burn prevention strategies and improved quality of care remain pivotal
      in reducing childhood burn morbidity and mortality in the developing countries. 

PMID- 24933575
TI  - Osteoplastic reconstruction of severely resorbed maxilla by stack plasty:
      combining sinus augmentation with lateral and vertical onlay bone grafting.
AB  - Progressive loss of the alveolus with aging leads to defects in the buccolingual
      and vertical dimensions. Maxillomandibular spatial discrepancies and deficits in
      sagittal facial projection develop at the same time as deficiencies of the
      periodontal unit, alveolar bone, and attached gingiva increase, depending on the
      extent of the atrophy. To restore the anatomy, a sinus lift should be combined
      with lateral and vertical bony augmentation in an osteoplastic procedure. To
      achieve this, "block over block" replacement with bone from the iliac crest
      allows precise functional and aesthetic restoration of the alveolus and the
      nasomaxillary region by combining inlay, interpositional, and onlay grafting. To
      our knowledge, preprosthetic osteoplastic reconstruction with stacked bone grafts
      has not previously been documented with a large number of patients. We report the
      results of this procedure in 62 patients with severe maxillary atrophy.

PMID- 24933576
TI  - How accurate are rapid prototyped (RP) final orthognathic surgical wafers? A
      pilot study.
AB  - Computer packages have been introduced to simulate the movements of the jaw in
      three dimensions to facilitate planning of treatment. After final 3-dimensional
      virtual planning, a rapid prototype wafer can be manufactured and used in
      theatre. Our aim was to assess the accuracy of rapid prototyping of virtual
      wafers derived from laser scanned dental models using CAD/CAM software. Upper and
      lower plaster models from 10 orthognathic patients, the articulated models, and
      the conventional wafers were scanned. The virtual wafers were made from CAD/CAM
      software, and printed on a stereolithographic printer. We also scanned the
      articulated models with rapid prototype wafers in place. The validity of the
      final rapid prototype wafer was measured by the accuracy with which upper and
      lower models related to one another. The absolute mean error of the rapid
      prototype wafer when aligned with the dental models was 0.94 (0.09) mm. The
      absolute distance of the 2 models articulated by conventional and rapid prototype
      wafers ranged from 0.04 - 1.73mm. The rapid prototype wafers were able to
      orientate the upper and lower dental models with an absolute mean error of 0.94
      (0.09) mm, but it ranged from 0.04-1.73mm.

PMID- 24933578
TI  - Adaptive evolution of an artificial RNA genome to a reduced ribosome environment.
AB  - The reconstitution of an artificial system that has the same evolutionary ability
      as a living thing is a major challenge in the in vitro synthetic biology. In this
      study, we tested the adaptive evolutionary ability of an artificial RNA genome
      replication system, termed the translation-coupled RNA replication (TcRR) system.
      In a previous work, we performed a study of the long-term evolution of the genome
      with an excess amount of ribosome. In this study, we continued the evolution
      experiment in a reduced-ribosome environment and observed that the mutant genome
      compensated for the reduced ribosome concentration. This result demonstrated the
      ability of the TcRR system to adapt and may be a step toward generating living
      things with evolutionary ability.

PMID- 24933577
TI  - P300 aberration in first-episode schizophrenia patients: a meta-analysis.
AB  - BACKGROUND: Decreased P300 amplitude is one of the most consistent findings in
      patients with schizophrenia. However, whether prolonged P300 latency occurs in
      patients with schizophrenia, especially first-episode schizophrenia (FES)
      patients, remains controversial. METHODS: A meta-analyses of P300 aberration in
      FES patients and healthy control(HC) group was conducted. The meta-regression
      analysis was performed using a random effects model. The pooled standardized
      effect size (PSES) was calculated as the division of the difference between the
      means of the two groups by the common standard deviation. RESULTS: A total of 569
      FES patients and 747 HCs were included in this meta-analysis. P300 amplitude was
      significantly reduced (PSES = -0.83, 95% CI: -1.02-0.65, P = 0.00001) and P300
      latency was delayed significantly in FES patients (PSES = -0.48, 95% CI: 0.14
      0.81, P = 0.005). The meta-regression analysis showed that task difficulty was a
      source of heterogeneity. CONCLUSIONS: The meta-analysis confirms that disrupted
      information processing is found in FES patients, which is manifested by smaller
      P300 amplitude and delayed P300 latency.

PMID- 24933579
TI  - Characterization of Viral Capsid Protein Self-Assembly around Short Single
      Stranded RNA.
AB  - For many viruses, the packaging of a single-stranded RNA (ss-RNA) genome is
      spontaneous, driven by capsid protein-capsid protein (CP) and CP-RNA
      interactions. Furthermore, for some multipartite ss-RNA viruses, copackaging of
      two or more RNA molecules is a common strategy. Here we focus on RNA copackaging
      in vitro by using cowpea chlorotic mottle virus (CCMV) CP and an RNA molecule
      that is short (500 nucleotides (nts)) compared to the lengths (~3000 nts)
      packaged in wild-type virions. We show that the degree of cooperativity of virus
      assembly depends not only on the relative strength of the CP-CP and CP-RNA
      interactions but also on the RNA being short: a 500-nt RNA molecule cannot form a
      capsid by itself, so its packaging requires the aggregation of multiple CP-RNA
      complexes. By using fluorescence correlation spectroscopy (FCS), we show that at
      neutral pH and sufficiently low concentrations RNA and CP form complexes that are
      smaller than the wild-type capsid and that four 500-nt RNAs are packaged into
      virus-like particles (VLPs) only upon lowering the pH. Further, a variety of bulk
      solution techniques confirm that fully ordered VLPs are formed only upon
      acidification. On the basis of these results, we argue that the observed high
      degree of cooperativity involves equilibrium between multiple CP/RNA complexes.

PMID- 24933580
TI  - Frontoparietal cognitive control of verbal memory recall in Alzheimer's disease.
AB  - OBJECTIVE: Episodic memory retrieval is reliant upon cognitive control systems,
      of which 2 have been identified with functional neuroimaging: a cingulo-opercular
      salience network (SN) and a frontoparietal executive network (EN). In Alzheimer's
      disease (AD), pathology is distributed throughout higher-order cortices. The
      hypotheses were that this frontoparietal pathology would impair activity
      associated with verbal memory recall; and that central cholinesterase inhibition
      (ChI) would modulate this, improving memory recall. METHODS: Functional magnetic
      resonance imaging was used to study normal participants and 2 patient groups:
      mild cognitive impairment (MCI) and AD. Activity within the EN and SN was
      observed during free recall of previously heard sentences, and related to
      measures of recall accuracy. RESULTS: In normal subjects, trials with reduced
      recall were associated with greater activity in both the SN and EN. Better recall
      was associated with greater activity in medial regions of the default mode
      network. By comparison, AD patients showed attenuated responses in both the SN
      and EN compared with either controls or MCI patients, even after recall
      performance was matched between groups. Following ChI, AD patients showed no
      modulation of activity within the SN, but increased activity within the EN. There
      was also enhanced activity within regions associated with episodic and semantic
      memory during less successful recall, requiring greater cognitive control.
      INTERPRETATION: The results indicate that in AD, impaired responses of cognitive
      control networks during verbal memory recall are partly responsible for reduced
      recall performance. One action of symptom-modifying treatment is partially to
      reverse the abnormal function of frontoparietal cognitive control and temporal
      lobe memory networks.

PMID- 24933581
TI  - Luminescent gold surfaces for sensing and imaging: patterning of transition metal
      probes.
AB  - Luminescent transition metal complexes are introduced for the microcontact
      printing of optoelectronic devices. Novel ruthenium(II), RubpySS, osmium(II),
      OsbpySS, and cyclometalated iridium(III), IrbpySS, bipyridyl complexes with long
      spacers between the surface-active groups and the metal were developed to reduce
      the distance-dependent, nonradiative quenching pathways by the gold surface.
      Indeed, surface-immobilized RubpySS and IrbpySS display strong red and green
      luminescence, respectively, on planar gold surfaces with luminescence lifetimes
      of 210 ns (RubpySS.Au) and 130 and 12 ns (83%, 17%) (IrbpySS.Au). The modified
      surfaces show enhancement of their luminescence lifetime in comparison with
      solutions of the respective metal complexes, supporting the strong luminescence
      signal observed and introducing them as ideal inorganic probes for imaging
      applications. Through the technique of microcontact printing, complexes were
      assembled in patterns defined by the stamp. Images of the red and green patterns
      rendered by the RubpySS.Au and IrbpySS.Au monolayers were revealed by
      luminescence microscopy studies. The potential of the luminescent surfaces to
      respond to biomolecular recognition events is demonstrated by addition of the
      dominant blood-pool protein, bovine serum albumin (BSA). Upon treatment of the
      surface with a BSA solution, the RubpySS.Au and IrbpySS.Au monolayers display a
      large luminescence signal increase, which can be quantified by time-resolved
      measurements. The interaction of BSA was also demonstrated by surface plasmon
      resonance (SPR) studies of the surfaces and in solution by circular dichroism
      spectroscopy (CD). Overall, the assembly of arrays of designed coordination
      complexes using a simple and direct MU-contact printing method is demonstrated in
      this study and represents a general route toward the manufacture of
      micropatterned optoelectronic devices designed for sensing applications. 

PMID- 24933582
TI  - Effects of a new piezoelectric device on periosteal microcirculation after
      subperiosteal preparation.
AB  - INTRODUCTION: Subperiosteal preparation using a periosteal elevator leads to
      disturbances of local periosteal microcirculation. Soft-tissue damage can usually
      be considerably reduced using piezoelectric technology. For this reason, we
      investigated the effects of a novel piezoelectric device on local periosteal
      microcirculation and compared this approach with the conventional preparation of
      the periosteum using a periosteal elevator. MATERIAL AND METHODS: A total of 20
      Lewis rats were randomly assigned to one of two groups. Subperiosteal preparation
      was performed using either a piezoelectric device or a periosteal elevator.
      Intravital microscopy was performed immediately after the procedure as well as
      three and eight days postoperatively. Statistical analysis of microcirculatory
      parameters was performed offline using analysis of variance (ANOVA) on ranks
      (p<0.05). RESULTS: At all time points investigated, intravital microscopy
      demonstrated significantly higher levels of periosteal perfusion in the group of
      rats that underwent piezosurgery than in the group of rats that underwent
      treatment with a periosteal elevator. CONCLUSION: The use of a piezoelectric
      device for subperiosteal preparation is associated with better periosteal
      microcirculation than the use of a conventional periosteal elevator. As a result,
      piezoelectric devices can be expected to have a positive effect on bone
      metabolism.

PMID- 24933583
TI  - Selection and evolution of resistance to antimicrobial drugs.
AB  - The overuse and misuse of antibiotics over many years has selected a high
      frequency of resistance among medically important bacterial pathogens. The
      evolution of resistance is complex, frequently involving multiple genetic
      alterations that minimize biological fitness costs and/or increase the resistance
      level. Resistance is selected at very low drug concentrations, such as found
      widely distributed in the environment, and this selects for resistant mutants
      with a high fitness. Once resistance with high fitness is established in a
      community it is very difficult to reduce its frequency. Addressing the problem of
      resistance is essential if we are to ensure a future where we can continue to
      enjoy effective medical control of bacterial infections. This will require
      several actions including the discovery and development of novel antibiotics, the
      creation of a continuous pipeline of drug discovery, and the implementation of
      effective global antibiotic stewardship to reduce the misuse of antibiotics and
      their release into the environment.

PMID- 24933584
TI  - Long-term monitoring of the human intestinal microbiota from the 2nd week to 13
      years of age.
AB  - Microbial contact begins prior to birth and continues rapidly thereafter. Few
      long term follow-up studies have been reported and we therefore characterized the
      development of intestinal microbiota of ten subjects from the 2nd week of life to
      13 years of age. PCR-denaturing gradient gel electrophoresis combined with
      several bacterial group-specific primer sets demonstrated the colonization steps
      of defined bacterial groups in the microbiota. Bifidobacterium species were seen
      throughout the test period in all subjects. Bacteroides fragilis group and
      Blautia coccoides-Eubacterium rectale group species were not detected in several
      subjects during the first 6 months of life but were commonly seen after 12 months
      of life. Streptococcus group appeared during early life but was not seen in
      several subjects at the age of 13 years. Although a few species were linked with
      the increasing age, major bacterial species in the groups did not change
      dramatically. Rather considerable changes were found in the relative abundances
      of each bacterial species. Clustering analysis of total bacterial flora indicated
      that the microbiota changed considerably between 6 months and 12 months of life,
      and, at the age of 12 months, the intestinal microbiota was already converted
      toward a profile characteristic of an adult microbiota. Probiotic supplementation
      in the beginning of life did not have major impacts on later microbiota
      development. 

PMID- 24933585
TI  - The identification of four histidine kinases that influence sporulation in
      Clostridium thermocellum.
AB  - In this study, we sought to identify genes involved in the onset of spore
      formation in Clostridium thermocellum via targeted gene deletions, gene over
      expression, and transcriptional analysis. We determined that three putative
      histidine kinases, clo1313_0286, clo1313_2735 and clo1313_1942 were positive
      regulators of sporulation, while a fourth kinase, clo1313_1973, acted as a
      negative regulator. Unlike Bacillus or other Clostridium species, the deletion of
      a single positively regulating kinase was sufficient to abolish sporulation in
      this organism. Sporulation could be restored in these asporogenous strains via
      overexpression of any one of the positive regulators, indicating a high level of
      redundancy between these kinases. In addition to having a sporulation defect,
      deletion of clo1313_2735 produced L-forms. Thus, this kinase may play an
      additional role in repressing L-form formation. This work suggests that C.
      thermocellum enters non-growth states based on the sensory input from multiple
      histidine kinases. The ability to control the development of non-growth states at
      the genetic level has the potential to inform strategies for improved strain
      development, as well as provide valuable insight into C. thermocellum biology. 

PMID- 24933586
TI  - Evaluation of 4-substituted styrenes as functional monomers for the synthesis of
      theophylline-specific molecularly imprinted polymers.
AB  - Six novel functional monomers: 4-(4-vinylphenyl)pyridine (M1), 4'-vinylbiphenyl-4
      ol (M2), N,N-dimethyl-4'-vinylbiphenyl-3-amine (M3), (4'-vinylbiphenyl-4
      yl)methanol (M4), 4'-vinylbiphenyl-4-carboxylic acid (M5) and 4-hydroxy-5-methyl
      4'-vinylbiphenyl-3-carboxylic acid (M6), were examined for their ability to
      imprint theophylline (1). Using a molecular modelling-NMR titration approach, M2
      and M6 were predicted to give rise to the most specific molecularly imprinted
      polymers (MIPs). Rebinding analysis suggests that no imprinting effect resulted
      from the polymerisation of monomers M1, M5 and M6, but modest to good levels of
      imprinting were evident from monomers M2, M3 and M4 with IF values ranging from
      1.1 (MIPM3, 20 mg) to 45 (MIPM2, 10 mg). The selective recognition of 1 varied as
      a function of polymer mass used. At low polymer loadings MIPM2 gave the very high
      IF of 45, reducing to IF = 4.1-2.3 at 20-40 mg polymer loading. With monomer M2,
      microwave synthesised MIP (MW-MIPM2) was examined. The MW-MIPM2 displayed lower
      specific rebinding than its conventionally produced counterpart (MIPM2) with IF
      values ranging from 1.6-2.3 (cf., MIPM2 IF 2.3-45), but significantly higher
      levels of rebinding with 25-52% of 1 rebound from a 0.080 mM CH3CN solution of 1
      (cf., MIPM2 5-25%). MW-MIPM2 displayed a lower BET surface area than MIPM2 (185
      m(2) g(-1)vs. 240 m(2) g(-1)), and lower surface (zeta) potential (-13.1 +/- 8.22
      mV vs. -31.4 +/- 4.84 mV). Freundlich isotherm analysis revealed that MW-MIPM2
      possessed higher affinity binding sites for 1 than MIPM2 with Kd values of 1.38
      and 2.31 respectively. In addition, MW-MIPM2 also exhibits a higher number of
      binding sites (NT) compared to MW-NIPM2 (0.72 and 0.41 mg g(-1), respectively).
      In specificity studies using caffeine (2), MIPM2 displayed a two-fold preference
      for rebinding of 1 and MW-MIPM2 a five-fold preference for 1 over 2. The quantity
      of 2 bound in both cases was consistent with non-specific binding events. In
      competitive rebinding experiments, increased discrimination in favour of 1 over 2
      was observed.

PMID- 24933587
TI  - Antidepressants are independently associated with gait deficits in single and
      dual task conditions.
AB  - OBJECTIVES: This study examined the relationships between late-onset depressive
      symptoms, antidepressants, and single and dual task gait in older adults. DESIGN:
      Cross-sectional study. SETTING: The Irish Longitudinal Study on Ageing (TILDA), a
      nationally representative cohort study. PARTICIPANTS: Community-dwelling adults
      aged 60 years and older, with Mini-Mental State Examination score >=24, no
      history of Parkinson's disease or early onset depression, and unaided completion
      of a gait assessment (N = 1,998). This study compared participants with and
      without potentially clinically relevant depressive symptoms (i.e., >=16 on the
      Centre for Epidemiological Studies Depression scale) and participants who were
      and were not on antidepressant therapy. MEASUREMENTS: Gait measures were obtained
      during single and dual task (reciting alternate letters of alphabet, A-C-E)
      walking using a 4.88 m GAITRite walkway. Regression analysis was used to examine
      the associations between each group and gait adjusting for sociodemographics and
      health. RESULTS: In the unadjusted models, depressive symptoms and antidepressant
      use were associated with gait deficits. After adjusting for covariates,
      antidepressant use was associated with reduced gait speed and stride length in
      single and dual task walking; depressive symptoms were not associated with any
      deficits. CONCLUSIONS: As gait impairments are associated with an increased risk
      of adverse outcomes including falls, clinicians should be aware of the impact of
      antidepressants on gait in older adults. Subsequent to this, interventions aimed
      at improving physical function, which is a known precursor to falls and
      functional disability, should be recommended.

PMID- 24933588
TI  - HJB-1, a 17-hydroxy-jolkinolide B derivative, inhibits LPS-induced inflammation
      in mouse peritoneal macrophages.
AB  - Jolkinolide B (JB) and 17-hydroxy-JB (HJB) are diterpenoids from plants and it
      has been reported that the presence of a C-17 hydroxy group in JB significantly
      enhances the anti-inflammatory potency of JB. In this study, two HJB derivatives
      HJB-1 and HJB-2 were generated by the chemical modification of a 17-hydroxy group
      of HJB. HJB-1 more effectively inhibited TNF-alpha, IL-1beta and IL-6 release in
      LPS-stimulated mouse peritoneal macrophages. In addition, HJB-1 reduced LPS
      induced mRNA expression of TNF-alpha, IL-1beta, IL-6, COX-2 and iNOS in a
      concentration-dependent manner, but did not alter IL-10 mRNA expression. LPS
      induced NF-kappaB activation and MAPK phosphorylation were also effectively
      inhibited by HJB-1. These results demonstrate that HJB-1 exerts anti-inflammatory
      effects on LPS-activated mouse peritoneal macrophages by inhibiting NF-kappaB
      activation and MAPK phosphorylation and modification of a 17-hydroxy group of HJB
      may enhance the anti-inflammatory potency of HJB derivatives. 

PMID- 24933590
TI  - Outpatient palliative care for chronic obstructive pulmonary disease: a case
      series.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have well
      documented symptoms that affect quality of life. Professional societies recommend
      palliative care for such patients, but the optimal way of delivering this care is
      unknown. OBJECTIVE: To describe an outpatient palliative medicine program for
      patients with COPD. DESIGN: Retrospective case series. SETTING/SUBJECTS: Thirty
      six patients with COPD followed in a United States academic outpatient palliative
      medicine clinic. MEASUREMENTS: Descriptive analysis of sociodemographic data,
      disease severity and comorbidities, treatments, hospitalizations, mortality,
      topic discussion, and symptom assessment. RESULTS: Thirty-six patients
      (representing 5% of the total number of patients with COPD seen in a specialty
      pulmonary clinic) were seen over 11 months and followed for 2 years. Seventy
      seven percent of patients were Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) stage 3-4 and 72% were on oxygen at home. No patients had
      documented advanced directives at the initial visit but documentation increased
      to 61% for those who had follow-up appointments. The most commonly documented
      topics included symptoms (100%), social issues (94%), psychological issues (78%),
      and advance care planning (75%). Of symptoms assessed, pain was the least
      prevalent (51.6%), and breathlessness and fatigue were the most prevalent (100%).
      Symptoms were often undertreated prior to the palliative care appointment. During
      the 3-year study period, there were 120 hospital admissions (median, 2) and 12
      deaths (33%). CONCLUSIONS: The patients with COPD seen in the outpatient
      palliative medicine clinic had many comorbid conditions, severe illness, and
      significant symptom burden. Many physical and psychological symptoms were
      untreated prior to the palliative medicine appointment. Whether addressing these
      symptoms through a palliative medicine intervention affects outcomes in COPD is
      unknown but represents an important topic for future research.

PMID- 24933591
TI  - The arthroscopic treatment of shoulder instability: bioabsorbable and standard
      metallic anchors produce equivalent clinical results.
AB  - PURPOSE: To investigate whether there are any differences in clinical outcomes
      and complications between absorbable and nonabsorbable suture anchors in the
      treatment of shoulder instability. METHODS: We performed a comprehensive search
      of Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature),
      Embase, and the Cochrane Central Registry of Controlled Trials, from inception of
      the databases, using various combinations of keywords. Only studies focusing on
      clinical outcomes of patients who underwent arthroscopic shoulder stabilization
      with suture anchors were selected. Two authors (R.P. and L.D.B.) then evaluated
      the methodologic quality of each article using the Coleman Methodology Score.
      RESULTS: Ten articles were included. Four were prospective randomized studies, 2
      were prospective cohort studies, and 4 were case series. The mean modified
      Coleman Methodology Score was 76.2. CONCLUSIONS: Given the overall good results
      reported after arthroscopic stabilization of the shoulder using different suture
      anchors, it is not possible to draw a definite and solid suggestion on which
      class of device is better advised for routine use. Thus the decision to use one
      of the anchor systems available may mostly depend on its cost-effectiveness,
      which should be the focus of future comprehensive research. LEVEL OF EVIDENCE:
      Level IV, systematic review of Level I to IV studies.

PMID- 24933592
TI  - A well-refined in vitro model derived from human embryonic stem cell for
      screening phytochemicals with midbrain dopaminergic differentiation-boosting
      potential for improving Parkinson's disease.
AB  - Stimulation of endogenous neurogenesis is a potential approach to compensate for
      loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in
      patients with Parkinson's disease (PD). This objective was to establish an in
      vitro model by differentiating pluripotent human embryonic stem cells (hESCs)
      into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA
      neurogenesis-boosting potentials. Consequently, a five-stage differentiation
      process was developed. The derived cells expressed many mDA markers including
      tyrosine hydroxylase (TH), beta-III tubulin, and dopamine transporter (DAT). The
      voltage-gated ion channels and dopamine release were also examined for verifying
      neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2
      (dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then,
      several potential phytochemicals including green tea catechins and ginsenosides
      were tested using the model. Finally, ginsenoside Rb1 was identified as the most
      potent phytochemical which is capable of upregulating neurotrophin expression and
      inducing mDA differentiation. 

PMID- 24933593
TI  - Sensitivity to social information, social referencing, and safety attitudes in a
      hazardous occupation.
AB  - Social referencing, or seeking information cues from others, occurs when a worker
      must make sense of those aspects of work, like safety hazards, that are
      ambiguous. This is a central argument of Social Information Processing Theory
      (SIPT), a social referencing and job characteristics theory of work attitudes.
      Adapting SIPT to the understanding of safety perceptions and attitudes, this
      paper hypothesizes relationships between the worker's sensitivity to social
      information, the worker's social safety cognitions, and the worker's own safety
      attitudes. Findings from a field study of workers in a hazardous occupation,
      emergency care/firefighting, confirmed SIPT-predicted relationships among these
      factors: the worker's belief in management's willingness to provide a safe work
      environment, the degree of risk the worker associates with his or her job, the
      worker's concern about the frequency of exposure to hazards, and the worker's
      personal experiences with hazards. These findings also suggest that a social
      referencing and job characteristics perspective like SIPT provides a logical and
      useful theoretical framework for understanding workers' interpretations of safety
      conditions. This perspective also helps relate theories of safety attitudes to a
      broad set of theories of social information and organizational behavior.

PMID- 24933594
TI  - The role of mindfulness and psychological capital on the well-being of leaders.
AB  - In today's highly competitive and extremely complex global economy,
      organizational leaders at all levels are facing unprecedented challenges. Yet,
      some seem to be handling the pressure better than others. Utilizing 4 samples of
      CEOs/presidents/top (n = 205), middle (n = 183), and junior (n = 202) managers,
      as well as 107 entrepreneurs, using Structural Equation Modeling we tested the
      direct effect that their level of mindfulness (heightened awareness) and the
      mediating effect of their psychological capital (i.e., hope, efficacy,
      resilience, and optimism) may have on their mental well-being. In all 4 samples,
      mindfulness was found to be negatively related to various dysfunctional outcomes
      such as anxiety, depression, and negative affect of the managerial leaders and
      burnout (i.e., emotional exhaustion and cynicism) of the entrepreneurs. For all 4
      samples, the model with psychological capital mediating the effects of
      mindfulness on dysfunctional outcomes fit the data best. The study limitations,
      future research and practical implications of these findings conclude the
      article.

PMID- 24933595
TI  - Civility norms, safety climate, and safety outcomes: a preliminary investigation.
AB  - Working environments that are both civil and safe are good for business and
      employee well-being. Civility has been empirically linked to such important
      outcomes as organizational performance and individuals' positive work-related
      attitudes, yet research relating civility to safety is lacking. In this study, we
      link perceptions of civility norms to perceptions of safety climate and safety
      outcomes. Drawing on social exchange theory, we proposed and tested a model in 2
      samples wherein civility norms indirectly relate to safety outcomes through
      associations with various safety climate facets. Our results supported direct
      relationships between civility and management safety climate and coworker safety
      climate. Additionally, indirect effects of civility norms on unsafe behaviors and
      injuries were observed. Indirect effects of civility norms on unsafe behaviors
      were observed through coworker safety climate and work-safety tension. Indirect
      effects of civility norms on injuries were observed through management safety
      climate and work-safety tension for full-time employees, although these effects
      did not hold for part-time employees. This study provides initial evidence that
      researchers and practitioners may want to look beyond safety climate to civility
      norms to more comprehensively understand the origins of unsafe behaviors and
      injuries and to develop appropriate preventive interventions.

PMID- 24933596
TI  - Unfinished tasks foster rumination and impair sleeping - particularly if leaders
      have high performance expectations.
AB  - This study examines the relationship between time pressure and unfinished tasks
      as work stressors on employee well-being. Relatively little is known about the
      effect of unfinished tasks on well-being. Specifically, excluding the impact of
      time pressure, we examined whether the feeling of not having finished the week's
      tasks fosters perseverative cognitions and impairs sleep. Additionally, we
      proposed that leader performance expectations moderate these relationships. In
      more detail, we expected the detrimental effect of unfinished tasks on both
      rumination and sleep would be enhanced if leader expectations were perceived to
      be high. In total, 89 employees filled out online diary surveys both before and
      after the weekend over a 5-week period. Multilevel growth modeling revealed that
      time pressure and unfinished tasks impacted rumination and sleep on the weekend.
      Further, our results supported our hypothesis that unfinished tasks explain
      unique variance in the dependent variables above and beyond the influence of time
      pressure. Moreover, we found the relationship between unfinished tasks and both
      rumination and sleep was moderated by leader performance expectations. Our
      results emphasize the importance of unfinished tasks as a stressor and highlight
      that leadership, specifically in the form of performance expectations,
      contributes significantly to the strength of this relationship.

PMID- 24933589
TI  - Key mediators in the immunopathogenesis of allergic asthma.
AB  - Asthma is described as a chronic inflammatory disorder of the conducting airways.
      It is characterized by reversible airway obstruction, eosinophil and Th2
      infiltration, airway hyper-responsiveness and airway remodeling. Our findings to
      date have largely been dependent on work done using animal models, which have
      been instrumental in broadening our understanding of the mechanism of the
      disease. However, using animals to model a uniquely human disease is not without
      its drawbacks. This review aims to examine some of the key mediators and cells of
      allergic asthma learned from animal models and shed some light on emerging
      mediators in the pathogenesis allergic airway inflammation in acute and chronic
      asthma. 

PMID- 24933597
TI  - Direct-to-patient laboratory test reporting: balancing access with effective
      clinical communication.

PMID- 24933598
TI  - A twin study of problematic internet use: its heritability and genetic
      association with effortful control.
AB  - Our goal was to estimate genetic and environmental sources of influence on
      adolescent problematic internet use, and whether these individual differences can
      be explained by effortful control, an important aspect of self-regulation. A
      sample of 825 pairs of Chinese adolescent twins and their parents provided
      reports of problematic internet use and effortful control. Univariate analysis
      revealed that genetic factors explained 58-66% of variance in problematic
      internet use, with the rest explained by non-shared environmental factors. Sex
      difference was found, suggesting boys' problematic internet use was more
      influenced by genetic influences than girls' problematic internet use. Bivariate
      analysis indicated that effortful control accounted for a modest portion of the
      genetic and non-shared environmental variance in problematic internet use among
      girls. In contrast, among boys, effortful control explained between 6% (parent
      report) and 20% (self-report) of variance in problematic internet use through
      overlapping genetic pathways. Adolescent problematic internet use is heritable,
      and poor effortful control can partly explain adolescent problematic internet
      use, with effects stronger for boys. Implications for future research are
      discussed. 

PMID- 24933599
TI  - Quo vadis polyplex?
AB  - Polymeric siRNA delivery has been an important field for the Journal of
      Controlled Release since the early 2000s. With currently about 1600 publications
      on this topic that can be found in Scopus, we have to ask ourselves why the
      clinical translation has been so slow. In this review we address the importance
      of in vivo studies, the problem of biocompatibility of the carrier systems,
      intracellular entrapment and endosomal release, as well as stability issues in
      the presence of serum. Most of all, we ask the question: Quo vadis? Where do
      polymeric carriers go inside the cell and inside the body and how does this
      affect repeated administration? We show that the gap of knowledge on polymer
      biodistribution and excretion has not been closed yet and needs to be addressed
      to develop safe RNAi therapeutics. 

PMID- 24933600
TI  - Issues and concerns in nanotech product development and its commercialization.
AB  - The revolutionary and ubiquitous nature of nanotechnology has fetched it a
      considerable attention in the past few decades. Even though its enablement and
      application to various sectors including pharmaceutical drug development is
      increasing with the enormous government aided funding for nanotechnology-based
      products, however the parallel commercialization of these systems has not picked
      up a similar impetus. The technology however does address the unmet needs of
      pharmaceutical industry, including the reformulation of drugs to improve their
      solubility, bioavailability or toxicity profiles as observed from the wide array
      of high-quality research publications appearing in various scientific journals
      and magazines. Based on our decade-long experience in the field of nanotech-based
      drug delivery systems and extensive literature survey, we perceive that the major
      hiccups to the marketing of these nanotechnology products can be categorized as
      1) inadequate regulatory framework; 2) lack of support and acceptance by the
      public, practicing physician, and industry; 3) developmental considerations like
      scalability, reproducibility, characterization, quality control, and suitable
      translation; 4) toxicological issues and safety profiles; 5) lack of available
      multidisciplinary platforms; and, 6) poor intellectual property protection. The
      present review dwells on these issues elaborating the trends followed by the
      industry, regulatory role of the USFDA and their implication, and the challenges
      set forth for a successful translation of these products from the lab and
      different clinical phases to the market.

PMID- 24933601
TI  - Lipid nanoparticles: drug localization is substance-specific and achievable load
      depends on the size and physical state of the particles.
AB  - Lipid nanoemulsions and -suspensions are being intensively investigated as
      carriers for poorly water soluble drugs. The question on where model compounds or
      probes are localized within the dispersions has been the subject of several
      studies. However, only little data exists for pharmaceutically relevant molecules
      in dispersions composed of pharmaceutically relevant excipients. In this work,
      the localization of drugs and drug-like substances was studied in lipid
      nanoemulsions and -suspensions. Conclusions about the drug localization were
      drawn from the relations between lipid mass, specific particle surface area and
      drug load in the dispersions. Additionally, the achievable drug loads of the
      liquid and the solid lipid particles were compared. Nanoemulsions and 
      suspensions comprised trimyristin as lipid matrix and poloxamer 188 as emulsifier
      and were prepared with different well-defined particle sizes. These pre-formed
      dispersions were passively loaded with either amphotericin B, curcumin,
      dibucaine, fenofibrate, mefenamic acid, propofol, or a porphyrin derivative. The
      physico-chemical properties of the particles were characterized; drug load and
      lipid content were quantified by UV spectroscopy and high performance liquid
      chromatography, respectively. For all drugs the passive loading procedure was
      successful in both emulsions and suspensions. Solid particles accommodate drug
      molecules preferably at the particle surface. Liquid particles can accommodate
      drugs at the particle surface as well as in the core; the distribution between
      the two sites is drug specific. It is also drug specific whether solid or liquid
      particles yield higher drug loads. As a general rule, smaller particles led to
      higher drug loads than larger ones. Propofol and the porphyrin derivative
      displayed eutectic interaction with the lipid and crystal growth after loading,
      respectively. 

PMID- 24933602
TI  - Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the
      brain.
AB  - The possibility of using genes as medicines to treat brain diseases is currently
      limited by the lack of safe and efficacious delivery systems able to cross the
      blood-brain barrier, thus resulting in a failure to reach the brain after
      intravenous administration. On the basis that iron can effectively reach the
      brain by using transferrin receptors for crossing the blood-brain barrier, we
      propose to investigate if a transferrin-bearing generation 3-polypropylenimine
      dendrimer would allow the transport of plasmid DNA to the brain after intravenous
      administration. In vitro, the conjugation of transferrin to the polypropylenimine
      dendrimer increased the DNA uptake by bEnd.3 murine brain endothelioma cells
      overexpressing transferrin receptors, by about 1.4-fold and 2.3-fold compared to
      that observed with the non-targeted dendriplex and naked DNA. This DNA uptake
      appeared to be optimal following 2h incubation with the treatment. In vivo, the
      intravenous injection of transferrin-bearing dendriplex more than doubled the
      gene expression in the brain compared to the unmodified dendriplex, while
      decreasing the non-specific gene expression in the lung. Gene expression was at
      least 3-fold higher in the brain than in any tested peripheral organs and was at
      its highest 24h following the injection of the treatments. These results suggest
      that transferrin-bearing polypropylenimine dendrimer is a highly promising gene
      delivery system to the brain. 

PMID- 24933603
TI  - Combination-targeting to multiple endothelial cell adhesion molecules modulates
      binding, endocytosis, and in vivo biodistribution of drug nanocarriers and their
      therapeutic cargoes.
AB  - Designing of drug nanocarriers to aid delivery of therapeutics is an expanding
      field that can improve medical treatments. Nanocarriers are often functionalized
      with elements that recognize cell-surface molecules involved in subcellular
      transport to improve targeting and endocytosis of therapeutics. Combination
      targeting using several affinity elements further modulates this outcome. The
      most studied example is endothelial targeting via multiple cell adhesion
      molecules (CAMs), which mimics the strategy of leukocytes to adhere and traverse
      the vascular endothelium. Yet, the implications of this strategy on intracellular
      transport and in vivo biodistribution remain uncharacterized. We examined this
      using nanocarriers functionalized for dual- or triple-targeting to intercellular,
      platelet-endothelial, and/or vascular CAMs (ICAM-1, PECAM-1, VCAM-1). These
      molecules differ in expression level, location, pathological stimulation, and/or
      endocytic pathway. In endothelial cells, binding of PECAM-1/VCAM-1-targeted
      nanocarriers was intermediate to single-targeted counterparts and enhanced in
      disease-like conditions. ICAM-1/PECAM-1-targeted nanocarriers surpassed PECAM
      1/VCAM-1 in control, but showed lower selectivity toward disease-like conditions.
      Triple-targeting resulted in binding similar to ICAM-1/PECAM-1 combination and
      displayed the highest selectivity in disease-like conditions. All combinations
      were effectively internalized by the cells, with slightly better performance when
      targeting receptors of different endocytic pathways. In vivo, ICAM-1/PECAM-1
      targeted nanocarriers outperformed PECAM-1/VCAM-1 in control and disease-like
      conditions, and triple-targeted counterparts slightly enhanced this outcome in
      some organs. As a result, delivery of a model therapeutic cargo (acid
      sphingomyelinase, deficient in Niemann-Pick disease A-B) was enhanced to all
      affected organs by triple-targeted nanocarriers, particularly in disease-like
      conditions. Therefore, multi-CAM targeting may aid the optimization of some
      therapeutic nanocarriers, where the combination and multiplicity of the affinity
      moieties utilized allow modulation of targeting performance. 

PMID- 24933604
TI  - Physiological stress reactivity and empathy following social exclusion: a test of
      the defensive emotional analgesia hypothesis.
AB  - Experiences of social exclusion elicit social pain responses. The current study
      examined the ability of social exclusion to activate physiological stress
      responses and adaptively modulate affect and empathy consistent with "defensive
      emotional analgesia." Measures of affect and empathy, and saliva samples for
      cortisol and alpha-amylase (sAA) analysis, were collected before and after
      subjects participated in a computer game ("Cyberball") designed to manipulate
      feelings of social exclusion. Contrary to our hypotheses, social exclusion was
      associated with a reduction in cortisol, and social inclusion with an increase in
      cortisol. Both Cyberball groups showed increases in sAA and decreases in both
      positive and negative affect, with the greatest drop in affect occurring after
      social exclusion. Empathy did not differ between the social exclusion and
      inclusion groups and was not correlated with cortisol or sAA levels. These
      results support the presence of a defensive response to social exclusion in which
      central stress pathways controlling cortisol release are inhibited. Cortisol and
      sAA were shown to have distinct patterns of responses to psychological stress,
      with sAA responding more rapidly. Related methodological concerns for the use of
      these physiological stress markers and of Cyberball in social neuroscience
      research are discussed. 

PMID- 24933605
TI  - BRAF(V600) mutation levels predict response to vemurafenib in metastatic
      melanoma.

PMID- 24933606
TI  - Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic
      melanoma.
AB  - BRAF and MEK inhibitors are not established treatments for non-V600 mutation
      positive metastatic melanoma. We carried out a retrospective analysis of efficacy
      and safety in four patients with BRAF K601E and one patient with L597Q mutation
      positive metastatic melanoma treated with the MEK inhibitor trametinib. Three
      patients achieved a RECIST partial response, including the patient with an L597Q
      mutation. Paired biopsies available in one of the five patients showed reduced
      phospho-ERK signalling and this corresponded to a metabolic response on F
      fluorodeoxyglucose-PET scanning. Trametinib toxicity was manageable. Trametinib
      has antitumour activity in patients with BRAF K601E and L597Q mutation-positive
      metastatic melanoma.

PMID- 24933607
TI  - Tyrosinase inhibitory activity of a glucosylated hydroxystilbene in mouse melan-a
      melanocytes.
AB  - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucopyranoside (1), isolated from
      Polygonum multiflorum, is a noncompetitive inhibitor of tyrosinase in cell-free
      kinetics; it reduced the Vmax values in a dose-dependent manner. Compound 1
      inhibited PKA-induced melanogenesis, reduced the protein expression of tyrosinase
      and its transcription factor, the microphthalmia-associated transcription factor,
      and lowered the complex formation between tyrosinase and tyrosinase-related
      protein 1 (TRP-1). Immunofluorescence microscopy revealed no association of
      tyrosinase with the endoplasmic reticulum or lysosomes, implying the absence of a
      direct effect of 1 on the maturation process of the enzyme. The antimelanogenic
      activity of 1 is likely mediated through a noncompetitive inhibition on
      tyrosinase, down-regulation of the expression of melanogenic proteins, and
      reduction of tyrosinase/TRP-1 complex formation.

PMID- 24933608
TI  - Transcranial regional cerebral oxygen desaturation predicts delayed cerebral
      ischaemia and poor outcomes after subarachnoid haemorrhage: a correlational
      study.
AB  - OBJECTIVES: To examine the relationship between regional cerebral oxygen
      saturation (rSO2), delayed cerebral ischaemia (DCI), and outcomes after
      aneurysmal subarachnoid haemorrhage (aSAH). RESEARCH METHODOLOGY: Subjects (n =
      163) with aSAH, age 21-75 years, and Fisher grade >1 were included in the study.
      Continuous rSO2 monitoring was performed for 5-10 days after injury using near
      infrared spectroscopy with sensors over the frontal/temporal cortex. rSO2<50
      indicated desaturation. DCI was defined as neurological deterioration due to
      impaired cerebral blood flow. Three- and 12-month functional outcomes were
      assessed by the modified Rankin scale (MRS) as good (0-3) and poor (4-6).
      RESULTS: DCI occurred in 57% of patients; of these 66% had rSO2<50. Overall, 56%
      had rSO2<50 on either side, 21% and 16% had poor MRS at 3 and 12 months. Subjects
      with rSO2 <50 were 3.25 times more likely to have DCI compared to those with rSO2
      >50 (OR 3.25, 95%CI 1.58-6.69), positive predictive value (PPV) = 70%. Subjects
      with rSO2 <50 were 2.7 times more likely to have poor 3-month MRS compared to
      those with rSO2 >50 (OR 2.7, 95%CI 1.1-7.2), PPV = 70%. CONCLUSIONS: These
      results suggest that NIRS has the potential for detecting DCI after aSAH. This
      potential needs to be further explored in a larger prospective study.

PMID- 24933609
TI  - Care, compassion and competence in critical care: a qualitative exploration of
      nurses' experience of family witnessed resuscitation.
AB  - This exploratory study was grounded in a local initiative promoting family
      witnessed resuscitation in the critical care units of a regional cardio-thoracic
      centre in the United Kingdom (UK). Research in this field has focussed on the
      perceived benefits, or otherwise, of family involvement, but little is known
      about the impact this has on critical care nurses or their practice. This study
      aimed to gain insights into nurses' experience of family witnessed resuscitation
      and identify any implications for critical care practices. The study employed a
      phenomenological approach and interviewed six nurses who had been involved in
      family witnessed resuscitation. Data from the transcribed interviews were
      analysed thematically and organised into descriptive categories which reflected
      the nursing experience of these resuscitation events. The three thematic
      categories generated by data analysis illustrate the challenges nurses faced in
      seeking to balance compassionate care and technical competence in emergency
      situations on critical care units. They also showed how nurses sought to
      reconcile unsettling emotions with their professional practice and
      responsibilities. The findings of this study are consistent with what is already
      known about the challenges of critical care nursing, but suggest that more
      research is needed to understand the practical and emotional complexities of
      family witnessed resuscitation. 

PMID- 24933610
TI  - Enhanced triterpene accumulation in Panax ginseng hairy roots overexpressing
      mevalonate-5-pyrophosphate decarboxylase and farnesyl pyrophosphate synthase.
AB  - To elucidate the function of mevalonate-5-pyrophosphate decarboxylase (MVD) and
      farnesyl pyrophosphate synthase (FPS) in triterpene biosynthesis, the genes
      governing the expression of these enzymes were transformed into Panax ginseng
      hairy roots. All the transgenic lines showed higher expression levels of PgMVD
      and PgFPS than that by the wild-type control. Among the hairy root lines
      transformed with PgMVD, M18 showed the highest level of transcription compared to
      the control (14.5-fold higher). Transcriptions of F11 and F20 transformed with
      PgFPS showed 11.1-fold higher level compared with control. In triterpene
      analysis, M25 of PgMVD produced 4.4-fold higher stigmasterol content (138.95
      MUg/100 mg, dry weight [DW]) than that by the control; F17 of PgFPS showed the
      highest total ginsenoside (36.42 mg/g DW) content, which was 2.4-fold higher
      compared with control. Our results indicate that metabolic engineering in P.
      ginseng was successfully achieved through Agrobacterium rhizogenes-mediated
      transformation and that the accumulation of phytosterols and ginsenosides was
      enhanced by introducing the PgMVD and PgFPS genes into the hairy roots of the
      plant. Our results suggest that PgMVD and PgFPS play an important role in the
      triterpene biosynthesis of P. ginseng. 

PMID- 24933611
TI  - Multi-peaked adaptive landscape for chikungunya virus evolution predicts
      continued fitness optimization in Aedes albopictus mosquitoes.
AB  - Host species-specific fitness landscapes largely determine the outcome of host
      switching during pathogen emergence. Using chikungunya virus (CHIKV) to study
      adaptation to a mosquito vector, we evaluated mutations associated with recently
      evolved sub-lineages. Multiple Aedes albopictus-adaptive fitness peaks became
      available after CHIKV acquired an initial adaptive (E1-A226V) substitution,
      permitting rapid lineage diversification observed in nature. All second-step
      mutations involved replacements by glutamine or glutamic acid of E2 glycoprotein
      amino acids in the acid-sensitive region, providing a framework to anticipate
      additional A. albopictus-adaptive mutations. The combination of second-step
      adaptive mutations into a single, 'super-adaptive' fitness peak also predicted
      the future emergence of CHIKV strains with even greater transmission efficiency
      in some current regions of endemic circulation, followed by their likely global
      spread. 

PMID- 24933613
TI  - TIR-domain-containing protein repertoire of nine anthozoan species reveals coral
      specific expansions and uncharacterized proteins.
AB  - The intracellular toll/interleukin-1 receptor (TIR) domain plays an important
      role in vertebrate immunity, but the evolution and function of invertebrate TIR
      domain-containing proteins is not fully understood. This study characterized and
      compared the TIR-domain-containing protein repertoire of nine cnidarians in class
      Anthozoa. A diverse set of proteins, including MyD88 (myeloid differentiation
      primary response protein 88), toll-like receptor (TLR)-like, interleukin-1
      receptor (IL-1R)-like, and TIR-only proteins are present in the species surveyed.
      Increased numbers of TIR-only proteins were observed in corals compared to
      anemones, especially in the Acroporid and Pocilloporid coral families. This
      expansion could be linked to diversity of the microbial community on or in hosts
      and managing both positive and negative associations. Phylogenetic analysis
      indicates there are two groups of proteins with IL-1R-like domain architecture in
      anthozoans that potentially evolved independently of the vertebrate family.
      Bacterial-like TIR_2 domain proteins are also present, including one sequence
      with novel domain architecture. Overall this work promotes a better understanding
      of the anthozoan immune repertoire, which is important in the context learning
      about ancestral immune pathways and host-microbe interactions. 

PMID- 24933615
TI  - Acquired subglottic stenosis: aetiological profile and treatment results.
AB  - OBJECTIVES: To analyse the aetiological profile and surgical results of patients
      with acquired chronic subglottic stenosis, and formulate a surgical scheme based
      on an audit of various surgical procedures. METHODS: Thirty patients were treated
      by 65 procedures (31 endoscopic and 34 external) between 2004 and 2009. RESULTS:
      Isolated subglottic stenosis was noted as unusual in the majority (27 cases),
      demonstrating contiguous tracheal or glottic involvement. The major aetiologies
      were intubation injury (n = 8) and external injury (n = 21) (i.e. blunt trauma,
      strangulation or penetrating injury). Vocal fold immobility and cartilage
      framework involvement were frequent with external injury and infrequent with
      intubation injury. Luminal restoration was achieved by endoscopic procedures in 2
      cases, external procedures in 19 cases, and external plus adjuvant endoscopic
      procedures in 8 cases. The preferred surgical options were: endoscopic
      procedures, restricted to short, recent, grade I or II mucosal stenosis cases;
      and external procedures for all other stenosis situations, including isolated
      subglottic (anterior cricoid split plus cartilage graft), subglottic and glottic
      or high subglottic (anterior plus posterior cricoid split with cartilage graft),
      and subglottic and tracheal (cricotracheal resection with anastomosis).
      CONCLUSIONS: External injury stenosis has a worse profile than intubation injury
      stenosis. Anatomical categorisation of subglottic stenosis guides surgical
      procedure selection. Endoscopic procedures have limited indications as primary
      procedures but are useful adjunctive procedures.

PMID- 24933614
TI  - Physiologic field triage criteria for identifying seriously injured older adults.
AB  - OBJECTIVE: To evaluate the ability of out-of-hospital physiologic measures to
      predict serious injury for field triage purposes among older adults and
      potentially reduce the undertriage of seriously injured elders to non-trauma
      hospitals. METHODS: This was a retrospective cohort study involving injured
      adults 55 years and older transported by 94 emergency medical services (EMS)
      agencies to 122 hospitals (trauma and non-trauma) in 7 regions of the western
      United States from January 1, 2006 to December 31, 2008. We evaluated initial out
      of-hospital Glasgow Coma Scale (GCS) score, systolic blood pressure (SBP),
      respiratory rate, heart rate, shock index (SBP / heart rate), out-of-hospital
      procedures, mechanism of injury, and patient demographics. The primary outcome
      was "serious injury," defined as Injury Severity Score (ISS) >= 16, as a measure
      of trauma center need. We used multivariable regression models, fractional
      polynomials and binary recursive partitioning to evaluate appropriate physiologic
      cut-points and the value of different physiologic triage criteria. RESULTS: A
      total of 44,890 injured older adults were evaluated and transported by EMS, of
      whom 2,328 (5.2%) had ISS >= 16. Nonlinear associations existed between all
      physiologic measures and ISS >= 16 (unadjusted and adjusted p <= 0.001 for all,),
      except for heart rate (adjusted p = 0.48). Revised physiologic triage criteria
      included GCS score <= 14; respiratory rate < 10 or > 24 breaths per minute or
      assisted ventilation; and SBP < 110 or > 200 mmHg. Compared to current triage
      practices, the revised criteria would increase triage sensitivity from 78.6 to
      86.3% (difference 7.7%, 95% CI 6.1-9.6%), reduce specificity from 75.5 to 60.7%
      (difference 14.8%, 95% CI 14.3-15.3%), and increase the proportion of patients
      without serious injuries transported to major trauma centers by 60%. CONCLUSIONS:
      Existing out-of-hospital physiologic triage criteria could be revised to better
      identify seriously injured older adults at the expense of increasing overtriage
      to major trauma centers.

PMID- 24933617
TI  - Return to Oz: voice pitch facilitates assessments of men's body size.
AB  - Listeners associate low voice pitch (fundamental frequency and/or harmonics) and
      formants (vocal-tract resonances) with large body size. Although formants
      reliably predict size within sexes, pitch does not reliably predict size in
      groups of same-sex adults. Voice pitch has therefore long been hypothesized to
      confound within-sex size assessment. Here we performed a knockout test of this
      hypothesis using whispered and 3-formant sine-wave speech devoid of pitch.
      Listeners estimated the relative size of men with above-chance accuracy from
      voiced, whispered, and sine-wave speech. Critically, although men's pitch and
      physical height were unrelated, the accuracy of listeners' size assessments
      increased in the presence rather than absence of pitch. Size assessments based on
      relatively low pitch yielded particularly high accuracy (70%-80%). Results of
      Experiment 2 revealed that amplitude, noise, and signal degradation of unvoiced
      speech could not explain this effect; listeners readily perceived formant shifts
      in manipulated whispered speech. Rather, in Experiment 3, we show that the denser
      harmonic spectrum provided by low pitch allowed for better resolution of
      formants, aiding formant-based size assessment. These findings demonstrate that
      pitch does not confuse body size assessment as has been previously suggested, but
      instead facilitates accurate size assessment by providing a carrier signal for
      vocal-tract resonances.

PMID- 24933616
TI  - Executive and perceptual attention play different roles in visual working memory:
      evidence from suffix and strategy effects.
AB  - Four experiments studied the interfering effects of a to-be-ignored "stimulus
      suffix" on cued recall of feature bindings for a series of objects. When each
      object was given equal weight (Experiment 1) or rewards favored recent items
      (Experiments 2 and 4), a recency effect emerged that was selectively reduced by a
      suffix. The reduction was greater for a "plausible" suffix with features drawn
      from the same set as the memory items, in which case a feature of the suffix was
      frequently recalled as an intrusion error. Changing payoffs to reward recall of
      early items led to a primacy effect alongside recency (Experiments 3 and 4).
      Primacy, like recency, was reduced by a suffix and the reduction was greater for
      a suffix with plausible features, such features often being recalled as intrusion
      errors. Experiment 4 revealed a tradeoff such that increased primacy came at the
      cost of a reduction in recency. These observations show that priority
      instructions and recency combine to determine a limited number of items that are
      the most accessible for immediate recall and yet at the same time the most
      vulnerable to interference. We interpret this outcome in terms of a labile,
      limited capacity "privileged state" controlled by both central executive
      processes and perceptual attention. We suggest further that this privileged state
      can be usefully interpreted as the focus of attention in the episodic buffer.

PMID- 24933618
TI  - Real-world interattribute distances lead to inefficient face gender
      categorization.
AB  - The processing of interattribute distances is believed to be critical for upright
      face categorization. A recent study by Taschereau-Dumouchel, Rossion, Schyns, and
      Gosselin (2010) challenged this idea by showing that participants were nearly at
      chance when asked to identify faces on the sole basis of real-world
      interattribute distances, while they were nearly perfect when all other facial
      cues were shown. However, it remains possible that humans are highly tuned to
      interattribute distances but that the information conveyed by these cues is
      scarce. We tested this hypothesis by contrasting the efficiencies-a measure of
      performance that factors out task difficulty-of 60 observers in 6 face gender
      categorization tasks. Our main finding is that efficiencies for faces that varied
      only in terms of their interattribute distances were an order of magnitude lower
      than efficiencies for faces that varied in all respects, except their
      interattribute distances, or in all respects. These results provide a definitive
      blow to the idea that real-world interattribute distances are critical for
      upright face processing. (PsycINFO Database Record (c) 2014 APA, all rights
      reserved). 

PMID- 24933619
TI  - beta1-Adrenergic blockers exert antioxidant effects, reduce matrix
      metalloproteinase activity, and improve renovascular hypertension-induced cardiac
      hypertrophy.
AB  - Hypertension induces left-ventricular hypertrophy (LVH) by mechanisms involving
      oxidative stress and unbalanced cardiac matrix metalloproteinase (MMP) activity.
      We hypothesized that beta1-adrenergic receptor blockers with antioxidant
      properties (nebivolol) could reverse hypertension-induced LVH more effectively
      than conventional beta1-blockers (metoprolol) when used at doses that exert
      similar antihypertensive effects. Two-kidney one-clip (2K1C) hypertension was
      induced in male Wistar rats. Six weeks after surgery, hypertensive and sham rats
      were treated with nebivolol (10 mg kg(-1)day(-1)) or metoprolol (20 mg kg(-1)day(
      1)) for 4 weeks. Systolic blood pressure was monitored weekly by tail-cuff
      plethysmography. LV structural changes and fibrosis were studied in
      hematoxylin/eosin- and picrosirius-stained sections, respectively. Cardiac MMP
      levels and activity were determined by in situ zymography, gel zymography, and
      immunofluorescence. Dihydroethidium and lucigenin-derived chemiluminescence
      assays were used to assess cardiac reactive oxygen species (ROS) production.
      Nitrotyrosine levels were determined in LV samples by immunohistochemistry and
      green fluorescence and were evaluated using the ImageJ software. Cardiac protein
      kinase B/Akt (AKT) phosphorylation state was assessed by Western blot. Both beta
      blockers exerted similar antihypertensive effects and attenuated hypertension
      induced cardiac remodeling. Both drugs reduced myocyte hypertrophy and collagen
      deposition in 2K1C rats. These effects were associated with lower cardiac ROS and
      nitrotyrosine levels and attenuation of hypertension-induced increases in cardiac
      MMP-2 levels and in situ gelatinolytic activity after treatment with both beta
      blockers. Whereas hypertension increased AKT phosphorylation, no effects were
      found with beta-blockers. In conclusion, we found evidence that two beta1
      blockers with different properties attenuate hypertension-induced LV hypertrophy
      and cardiac collagen deposition in association with significant cardiac
      antioxidant effects and MMP-2 downregulation, thus suggesting a critical role for
      beta1-adrenergic receptors in mediating those effects. Nebivolol is not superior
      to metoprolol, at least with respect to their capacity to reverse hypertension
      induced LVH.

PMID- 24933621
TI  - The properties of capillary columns with silica organic-inorganic MCM-41 type
      porous layer stationary phase.
AB  - In this work, we report the method of capillary columns preparation for gas-solid
      chromatography with a porous layer of MCM-41 type silica sorbent. The porous
      layer was synthesized by the sol-gel method inside the column. Scanning electron
      microscopy (SEM) measurements were performed to obtain information about the
      porous layer. The loading capacity of the prepared columns was investigated. An
      adsorbent selectivity was changed by using different relative contents of organic
      inorganic precursors: vinyltriethoxysilane (VTEOS) and tetraethoxysilane (TEOS).
      Properties of the columns prepared are discussed. Separating examples of C1-C4
      hydrocarbons and some other compounds are presented.

PMID- 24933620
TI  - Critical cysteines in Akt1 regulate its activity and proteasomal degradation:
      implications for neurodegenerative diseases.
AB  - Impaired Akt1 signaling is observed in neurodegenerative diseases, including
      Parkinson's disease (PD). In PD models oxidative modification of Akt1 leads to
      its dephosphorylation and consequent loss of its kinase activity. To explore the
      underlying mechanism we exposed Neuro2A cells to cadmium, a pan inhibitor of
      protein thiol disulfide oxidoreductases, including glutaredoxin 1 (Grx1), or
      downregulated Grx1, which led to dephosphorylation of Akt1, loss of its kinase
      activity, and also decreased Akt1 protein levels. Mutation of cysteines to
      serines at 296 and 310 in Akt1 did not affect its basal kinase activity but
      abolished cadmium- and Grx1 downregulation-induced reduction in Akt1 kinase
      activity, indicating their critical role in redox modulation of Akt1 function and
      turnover. Cadmium-induced decrease in phosphorylated Akt1 correlated with
      increased association of wild-type (WT) Akt1 with PP2A, which was absent in the
      C296-310S Akt1 mutant and was also abolished by N-acetylcysteine treatment.
      Further, increased proteasomal degradation of Akt1 by cadmium was not seen in the
      C296-310S Akt1 mutant, indicating that oxidation of cysteine residues facilitates
      degradation of WT Akt1. Moreover, preventing oxidative modification of Akt1
      cysteines 296 and 310 by mutating them to serines increased the cell survival
      effects of Akt1. Thus, in neurodegenerative states such as PD, maintaining the
      thiol status of cysteines 296 and 310 in Akt1 would be critical for Akt1 kinase
      activity and for preventing its degradation by proteasomes. Preventing
      downregulation of Akt signaling not only has long-range consequences for cell
      survival but could also affect the multiple roles that Akt plays, including in
      the Akt-mTOR signaling cascade. 

PMID- 24933622
TI  - Covalent immobilization of graphene onto stainless steel wire for jacket-free
      stir bar sorptive extraction.
AB  - Stainless steel wire is a good substrate for jacket-free stir bar sorptive
      extraction (SBSE). In this work, we present the first example of chemical
      modification of graphene on stainless steel wire (SSW) for SBSE. Bio-inspired
      polydopamine was firstly modified on the SSW covalently; then graphene oxide was
      introduced and reacted with amino groups of polydopamine layer. The modification
      of polydopamine and graphene can be repeated by a layer-by-layer strategy,
      resulting in control of the thickness of graphene layer and increase of
      extraction capability. The prepared covalently immobilized graphene-stainless
      steel wire (G-SSW) exhibited good stability under stirring, ultrasonication and
      treatment with commonly used organic solvents, basic and acidic solutions.
      Application as stir bar for SBSE, G-SSW was found to possess good extraction
      efficiency towards pollutant polyaromatic hydrocarbons (PAHs), with enrichment
      factors from 10086 to 16896. After optimization of conditions, G-SSW based SBSE
      was coupled HPLC for determination of PAHs in environmental and food samples. The
      quantitative method has low limits of detection of 0.2-50pg/mL, which is better
      than some reported SBSE-HPLC methods. The method shows wide linear range (200
      5000, 10-1000 and 1-1000pg/mL), good linearity (r>=0.9950) and good
      reproducibility (RSD<=4.97%). The method has been applied to soil and food
      samples, with good selectivity and good recoveries ranging from 88.5-113.6%.

PMID- 24933623
TI  - Number of erythrocyte transfusions is more predictive than serum ferritin in
      estimation of cardiac iron loading in pediatric patients with acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Transfusions with packed erythrocytes is a common practice in
      pediatric patients with acute lymphoblastic leukemia (ALL) who are on
      chemotherapy. Since there is no physiological excretion mechanism for iron, the
      iron related to erythrocyte transfusions accumulates and may contribute to late
      cardiac, hepatic and endocrine complications in these patients. PROCEDURE: In
      order to evaluate the iron burden among pediatric patients with ALL and define
      the risk factors associated with higher iron loading, we evaluated 79 pediatric
      patients with ALL (36 were off-therapy). Cardiac and hepatic T2* were ordered to
      a total of 22 (28%) patients who were either transfused with erythrocytes >= 10
      times (n=11; 50%), had serum ferritin (SF) >= 1000 ng/ml (n=2; 9.1%) or both
      (n=9; 40.9%). RESULTS: Half of the patients who were screened by T2* MRI had
      hepatic T2*<7 ms and six (27%) of the patients had cardiac T2*<20 ms, indicating
      iron loading. Patients who had serum ferritin <1000 vs >= 1000 ng/ml had median
      cardiac T2* values of 28.3 ms (15-40) vs 21 (7.9-36), (p=0.324); whereas hepatic
      T2* of 10.8 (5.32-27) vs 4.7 (2.2-36), (p=0.017). Patients who had erythrocyte
      transfusion <10 vs >= 10 times had median cardiac T2* values of 34 ms (28-38) vs
      23 (7.93-40), (p=0.021); whereas hepatic T2* of 13.6 (6.6-36) vs 5.32 (2.2-27),
      (p=0.046). CONCLUSIONS: Our results indicate that pediatric patients with ALL
      should be screened for transfusional iron load and the amount of erythrocyte
      transfusions seems to be a more reliable indication than serum ferritin levels to
      detect cardiac iron loading in these patients.

PMID- 24933624
TI  - Passion fruit peel extract attenuates bleomycin-induced pulmonary fibrosis in
      mice.
AB  - Idiopathic pulmonary fibrosis is a progressive fatal lung disease characterized
      by excessive collagen deposition, with no effective treatments. We investigated
      the efficacy of natural products with high anti-inflammatory activity, such as
      passion fruit peel extract (PFPE), in a mouse model of bleomycin-induced
      pulmonary fibrosis (PF). C57BL/6J mice were subjected to a single intratracheal
      instillation of bleomycin to induce PF. Daily PFPE treatment significantly
      reduced loss of body mass and mortality rate in mice compared with those treated
      with bleomycin. While bleomycin-induced PF resulted in elevated total numbers of
      inflammatory cells, macrophages, lymphocytes, and neutrophils in bronchoalveolar
      lavage fluid on both days 7 and 21, PFPE administration significantly attenuated
      these phenomena compared with bleomycin group. On day 7, the decreased superoxide
      dismutase and myeloperoxidase activities observed in the bleomycin group were
      significantly restored with PFPE treatment. On day 21, enhanced hydroxyproline
      deposition in the bleomycin group was also suppressed by PFPE administration.
      PFPE treatment significantly attenuated extensive inflammatory cell infiltration
      and accumulation of collagen in lung tissue sections of bleomycin-induced mice on
      days 7 and 21, respectively. Our results indicate that administration of PFPE
      decreased bleomycin-induced PF because of anti-inflammatory and antioxidant
      activities. 

PMID- 24933625
TI  - Transition from stripe-like patterns to a particulate film using driven
      evaporating menisci.
AB  - Better control of colloidal assembly by convective deposition is particularly
      helpful in particle templating. However, knowledge of the different factors that
      can alter colloidal patterning mechanisms is still insufficient. Deposit
      morphology is strongly ruled by contact line dynamics, but the wettability
      properties of the substrate can alter it drastically. In this work, we
      experimentally examined the roles of substrate contact angle hysteresis and
      receding contact angle using driven evaporating menisci similar to the dip
      coating technique but at a low capillary number. We used smooth substrates with
      very different wettability properties and nanoparticles of different sizes. For
      fixed withdrawal velocity, evaporation conditions, and nanoparticle
      concentration, we analyzed the morphology of the deposits formed on each
      substrate. A gradual transition from stripe-like patterns to a film was observed
      as the contact angle hysteresis and receding contact angle were lowered. 

PMID- 24933626
TI  - Information integration without awareness.
AB  - Information integration and consciousness are closely related, if not
      interdependent. But, what exactly is the nature of their relation? Which forms of
      integration require consciousness? Here, we examine the recent experimental
      literature with respect to perceptual and cognitive integration of
      spatiotemporal, multisensory, semantic, and novel information. We suggest that,
      whereas some integrative processes can occur without awareness, their scope is
      limited to smaller integration windows, to simpler associations, or to ones that
      were previously acquired consciously. This challenges previous claims that
      consciousness of some content is necessary for its integration; yet it also
      suggests that consciousness holds an enabling role in establishing integrative
      mechanisms that can later operate unconsciously, and in allowing wider-range
      integration, over bigger semantic, spatiotemporal, and sensory integration
      windows. 

PMID- 24933627
TI  - Does recent sexual intercourse during pregnancy affect the results of the fetal
      fibronectin rapid test? A comparative prospective study.
AB  - OBJECTIVE: We conducted a prospective comparative cohort study to determinate the
      influence of coitus on quantitative fetal fibronectin test results under normal
      pregnancy conditions. We also compared values obtained in cervical and vaginal
      secretions. METHODS: In a population of women with normal singleton pregnancies
      between 22 and 28 weeks gestation, we have performed (cervical and vaginal)
      quantitative fetal fibronectin tests in two separate groups classified according
      to timing after coitus (one group of women had intercourse within 24 h before
      sampling and the control group had intercourse >24 h before sampling). The main
      outcome measures were the proportion of positive tests in both groups and the
      correlation between cervical and vaginal values through the Pearson correlation
      coefficient. RESULTS: Both groups were similar in terms of general
      characteristics and pregnancy outcomes. The proportions of positive results in
      the vaginal secretions were 7.5% and 25.0% (P=0.007) in the control and coitus
      group, respectively. In the cervical secretions, the proportions of positive
      tests were greater, but not statistically different (39.7% and 40.0%,
      respectively). The Pearson correlation coefficients were very low (<0.3)
      indicating poor correlation between both sampling locations. Even if the cervical
      values were generally greater than the vaginal values, they were lower in 26% of
      the women. CONCLUSIONS: Coitus definitely interferes with vaginal fetal
      fibronectin test results. In cervical secretions, the positive rate was so high
      that coitus had no influence, but cervical sampling in this location should be
      avoided.

PMID- 24933628
TI  - New laboratory markers for the management of rheumatoid arthritis patients.
AB  - Rheumatoid arthritis, the most prominent of systemic autoimmune rheumatic
      diseases, represents an important social health problem. Recent insights into the
      immunopathogenic mechanism of this complex and multiform illness might open new
      perspectives for a more appropriate laboratory approach. In this review we focus
      on the most relevant pathogenetic mechanism; indicating the laboratory biomarkers
      specifically linked to early diagnosis, prognosis, evolutive aspects of the
      disease, and therapeutic efficacy. Evidence based on laboratory medicine could
      provide the best outcome for patients.

PMID- 24933629
TI  - Validity and reliability of the 13C-methionine breath test for the detection of
      moderate hyperhomocysteinemia in Mexican adults; statistical issues in validity
      and reliability analysis.

PMID- 24933630
TI  - The serum uromodulin level is associated with kidney function.
AB  - BACKGROUND: In chronic kidney diseases of various etiologies, the urinary
      excretion of uromodulin is usually decreased in parallel with the glomerular
      filtration rate. This study aimed to investigate whether serum uromodulin is
      associated with kidney function. METHODS: Within the framework of the Seniorlabor
      study, a subset of subjectively healthy individuals 60 years of age and older
      were included in the study. Serum uromodulin was measured with ELISA. The
      relationship between serum uromodulin and different stages of kidney function
      (i.e., cystatin C-based 2012-CKD-EPI eGFRCysC>90 mL/min/1.73 m2, 60-89
      mL/min/1.73 m2, 45-59 mL/min/1.73 m2, and <45 mL/min/1.73 m2) was investigated.
      Furthermore, the relationship between serum uromodulin and other markers of
      kidney function (i.e., creatinine, cystatin C, and urea) was assessed. RESULTS:
      In total, 289 participants (140 males/149 females; mean age 71+/-7 years) were
      included in the study. There were significant differences in serum uromodulin
      among the four groups according to different kidney function stages (p<0.001).
      Serum uromodulin displayed inverse relationships with creatinine (r=-0.39),
      cystatin C (r=-0.42), and urea (r=-0.30) and, correspondingly, a positive
      relationship with eGFRCysC (r=0.38, p<0.001 for all). These associations remained
      intact when fitting a regression model that incorporated age, gender, body mass
      index, and current smoking status as covariates. CONCLUSIONS: Serum uromodulin
      behaves in a manner opposite that of the different conventional renal retention
      markers by displaying lower concentrations with decreasing kidney function. As
      uromodulin is produced by the cells of the thick ascending limb of the loop of
      Henle, lower uromodulin serum levels may reflect a reduction in number or
      function of these cells in chronic kidney disease.

PMID- 24933631
TI  - Comparison of statistical methods for finding network motifs.
AB  - There has been much recent interest in systems biology for investigating the
      structure of gene regulatory systems. Such networks are often formed of specific
      patterns, or network motifs, that are interesting from a biological point of
      view. Our aim in the present paper is to compare statistical methods specifically
      with regard to the question of how well they can detect such motifs. One popular
      approach is by network analysis with Gaussian graphical models (GGMs), which are
      statistical models associated with undirected graphs, where vertices of the graph
      represent genes and edges indicate regulatory interactions. Gene expression
      microarray data allow us to observe the amount of mRNA simultaneously for a large
      number of genes p under different experimental conditions n, where p is usually
      much larger than n prohibiting the use of standard methods. We therefore compare
      the performance of a number of procedures that have been specifically designed to
      address this large p-small n issue: G-Lasso estimation, Neighbourhood selection,
      Shrinkage estimation using empirical Bayes for model selection, and PC-algorithm.
      We found that all approaches performed poorly on the benchmark E. coli network.
      Hence we systematically studied their ability to detect specific network motifs,
      pairs, hubs and cascades, in extensive simulations. We conclude that all methods
      have difficulty detecting hubs, but the PC-algorithm is most promising.

PMID- 24933632
TI  - Morphological variations of the anterior thoracic skeleton and their forensic
      significance: radiographic findings in a Spanish autopsy sample.
AB  - The anterior thoracic skeleton may exhibit a number of morphological variations
      or anomalies, including accessory ossicles, atypical fusion or nonfusion of bony
      segments, and accessory foramina. Awareness of these minor skeletal variants is
      important in forensic medicine given that they may be mistakenly identified as
      pathological or traumatic lesions. The identification of subtle morphological
      anomalies may also aid in the process of individualization by serving as points
      of similarity if their occurrence was recorded antemortem. This study assessed
      the prevalence of anatomical variants of the sternum and ribs in a modern
      population from Spain, since the frequency of these skeletal anomalies differs
      between population groups. The occurrence of sternal clefts and foramina,
      bifurcated ribs, fusion of the manubriosternal and sternoxiphoidal junctions, and
      type of xiphoid process end was evaluated on posterior-anterior digital
      radiographs. None of the morphological variations were associated with sex or
      age, with the exception of two traits related to the xiphoid process. The xiphoid
      process was absent more often in younger individuals, particularly specimens
      below the age of 30 years, whereas, complete fusion of the sternoxiphoidal
      junction was more often observed in individuals above 50 years of age. However,
      these morphological variants are highly variable in the study sample and thus
      they have limited utility in forensic age estimation in the Spanish population.
      Nonetheless, the presence of various morphological anomalies such as sternal
      foramina, bifid ribs, and triple-ended xiphoid processes may provide information
      useful for establishing a personal identification. 

PMID- 24933633
TI  - The identification of an impurity product, 4,6-dimethyl-3,5-diphenylpyridin-2-one
      in an amphetamine importation seizure, a potential route specific by-product for
      amphetamine synthesized by the APAAN to P2P, Leuckart route.
AB  - During the analysis of a Customs' importation case for the suspected presence of
      controlled drugs, amphetamine was found to be present. The samples were also
      found to contain by-products from the amphetamine synthesis and these included
      benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N
      formylamphetamine, a pair of naphthalene derivatives and amphetamine dimers.
      During the experimental investigation of the naphthalenes formation, a series of
      syntheses involved the acid hydrolysis of alpha-phenylacetoacetonitrile (APAAN).
      In one such experiment with sulfuric acid, a white substance was visibly
      deposited on the glassware and this was identified as the pyridone derivative,
      4,6-dimethyl-3,5-diphenylpyridin-2-one. This compound was subsequently found to
      be present in the amphetamine product seized by the Customs and also in the final
      product of our own laboratory synthesized amphetamine (APAAN hydrolyzed to
      P2P/Leuckart reaction). Interestingly, the, 4,6-dimethyl-3,5-diphenylpyridin-2
      one was not found when commercially supplied P2P underwent the Leuckart reaction
      to yield amphetamine. This suggests that 4,6-dimethyl-3,5-diphenylpyridin-2-one
      may be a route specific marker to the use of APAAN as a starting material in the
      synthesis of P2P and subsequent Leuckart reaction to yield amphetamine. 

PMID- 24933634
TI  - Brain metastases from lung cancer show increased expression of DVL1, DVL3 and
      beta-catenin and down-regulation of E-cadherin.
AB  - The susceptibility of brain to secondary formation from lung cancer primaries is
      a well-known phenomenon. In contrast, the molecular basis for invasion and
      metastasis to the brain is largely unknown. In the present study, 31 brain
      metastases that originated from primary lung carcinomas were analyzed regarding
      over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1)
      and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by
      immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase
      chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to
      investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in
      brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was
      observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the
      Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the
      nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of
      cases with nuclear beta-catenin significantly increased (p=0.0001). Down
      regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed
      36% of samples with LOH of the CDH1. In comparison to other lung cancer
      pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were
      significantly associated to CDH1 LOH (p=0.001). Microsatellite instability was
      detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not
      targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta
      catenin were present in brain metastases which indicates that Wnt signaling is
      important and may contribute to better understanding of genetic profile
      conditioning lung cancer metastasis to the brain.

PMID- 24933635
TI  - Sperm-egg fusion: a molecular enigma of mammalian reproduction.
AB  - The mechanism of gamete fusion remains largely unknown on a molecular level
      despite its indisputable significance. Only a few of the molecules required for
      membrane interaction are known, among them IZUMO1, which is present on sperm,
      tetraspanin CD9, which is present on the egg, and the newly found oolema protein
      named Juno. A concept of a large multiprotein complex on both membranes forming
      fusion machinery has recently emerged. The Juno and IZUMO1, up to present, is the
      only known extracellular receptor pair in the process of fertilization, thus,
      facilitating the essential binding of gametes. However, neither IZUMO1 nor Juno
      appears to be the fusogenic protein. At the same time, the tetraspanin is
      expected to play a role in organizing the egg membrane order and to interact
      laterally with other factors. This review summarizes, to present, the known
      molecules involved in the process of sperm-egg fusion. The complexity and
      expected redundancy of the involved factors makes the process an intricate and
      still poorly understood mechanism, which is difficult to comprehend in its full
      distinction. 

PMID- 24933637
TI  - Weighted risk score-based multifactor dimensionality reduction to detect gene
      gene interactions in nasopharyngeal carcinoma.
AB  - Determining the complex relationships between diseases, polymorphisms in human
      genes and environmental factors is challenging. Multifactor dimensionality
      reduction (MDR) has been proven to be capable of effectively detecting the
      statistical patterns of epistasis, although classification accuracy is required
      for this approach. The imbalanced dataset can cause seriously negative effects on
      classification accuracy. Moreover, MDR methods cannot quantitatively assess the
      disease risk of genotype combinations. Hence, we introduce a novel weighted risk
      score-based multifactor dimensionality reduction (WRSMDR) method that uses the
      Bayesian posterior probability of polymorphism combinations as a new quantitative
      measure of disease risk. First, we compared the WRSMDR to the MDR method in
      simulated datasets. Our results showed that the WRSMDR method had reasonable
      power to identify high-order gene-gene interactions, and it was more effective
      than MDR at detecting four-locus models. Moreover, WRSMDR reveals more
      information regarding the effect of genotype combination on the disease risk, and
      the result was easier to determine and apply than with MDR. Finally, we applied
      WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a
      statistically significant high-order interaction among three polymorphisms:
      rs2860580, rs11865086 and rs2305806. 

PMID- 24933636
TI  - Carriers in cell-based therapies for neurological disorders.
AB  - There is a pressing need for long-term neuroprotective and neuroregenerative
      therapies to promote full function recovery of injuries in the human nervous
      system resulting from trauma, stroke or degenerative diseases. Although cell
      based therapies are promising in supporting repair and regeneration, direct
      introduction to the injury site is plagued by problems such as low transplanted
      cell survival rate, limited graft integration, immunorejection, and tumor
      formation. Neural tissue engineering offers an integrative and multifaceted
      approach to tackle these complex neurological disorders. Synergistic therapeutic
      effects can be obtained from combining customized biomaterial scaffolds with cell
      based therapies. Current scaffold-facilitated cell transplantation strategies aim
      to achieve structural and functional rescue via offering a three-dimensional
      permissive and instructive environment for sustainable neuroactive factor
      production for prolonged periods and/or cell replacement at the target site. In
      this review, we intend to highlight important considerations in biomaterial
      selection and to review major biodegradable or non-biodegradable scaffolds used
      for cell transplantation to the central and peripheral nervous system in
      preclinical and clinical trials. Expanded knowledge in biomaterial properties and
      their prolonged interaction with transplanted and host cells have greatly
      expanded the possibilities for designing suitable carrier systems and the
      potential of cell therapies in the nervous system. 

PMID- 24933639
TI  - Cytotoxic effects of dillapiole on embryonic development of mouse blastocysts in
      vitro and in vivo.
AB  - We examined the cytotoxic effects of dillapiole, a phenylpropanoid with
      antileishmanial, anti-inflammatory, antifungal, and acaricidal activities, on the
      blastocyst stage of mouse embryos, subsequent embryonic attachment and outgrowth
      in vitro, and in vivo implantation via embryo transfer. Blastocysts treated with
      2.5-10 MUM dillapiole exhibited a significant increase in apoptosis and
      corresponding decrease in total cell number. Notably, the implantation success
      rates of blastocysts pretreated with dillapiole were lower than those of their
      control counterparts. Moreover, in vitro treatment with 2.5-10 MUM dillapiole was
      associated with increased resorption of post-implantation embryos and decreased
      fetal weight. Our results collectively indicate that dillapiole induces apoptosis
      and retards early post-implantation development, both in vitro and in vivo.
      However, the extent to which this organic compound exerts teratogenic effects on
      early human development is not known at present. Further studies are required to
      establish effective protection strategies against the cytotoxic effects of
      dillapiole. 

PMID- 24933638
TI  - Damage of neuroblastoma cell SH-SY5Y mediated by MPP+ inhibits proliferation of T
      cell leukemia Jurkat by co-culture system.
AB  - The adaptive immune system has implications in pathology of Parkinson's disease
      (PD). Research data demonstrated that the peripheral CD4+ T-cell population
      decreased in pathogenesis of PD. The effect of damaged dopaminergic neurons on
      peripheral T cells of PD is still unknown. In this study, we constructed a
      neuronal and glial cells co-culture model by using human neuroblastoma cells SH
      SY5Y and gliomas cells U87. After the co-culture cells were treated with
      neurotoxin 1-methyl-4-phenylpyridinium (MPP+) for 24 h, the conditioned media was
      harvested and used to cultivate T-cell leukemia Jurkat cells for another 24 h. We
      then analyzed the cell proliferation, cell cycle and necrosis effect of Jurkat
      cells. The results showed that co-culture medium of SH-SY5Y and U87 cells with
      MPP+ treatment inhibited the proliferation of Jurkat cells compared to control
      medium without MPP+, even though the same concentration of MPP+ had very little
      toxicity to the Jurkat cell. Furthermore, co-culture medium with low
      concentration of MPP+ (100 uM) arrested Jurkat cells cycle in G2/M phase through
      increasing cell cycle division 2 (CDC2) and CyclinB1 expression level, whereas co
      culture medium with high concentration of MPP+ (500 uM) induced Jurkat cell
      necrosis through cellular swelling and membrane breakage. Our data implies that
      damaged dopamine neurons with glial cells can lead to the reduced number or
      inhibited proliferation activity of peripheral T cells. 

PMID- 24933640
TI  - Role of Candida albicans-secreted aspartyl proteinases (Saps) in severe early
      childhood caries.
AB  - Candida albicans is strongly associated with severe early childhood caries (S
      ECC). However, the roles of secreted aspartyl proteinases (Saps), an important
      virulence factor of C. albicans, in the progress of S-ECC are not clear. In our
      study, the Saps activities were evaluated by the yeast nitrogen base-bovine serum
      albumi (YNB-BSA) agar plate method and by the MTT method with bovine serum
      albumin (BSA) as the substrate. Genotypes of C. albicans and gene expression of
      Sap1-5 were evaluated. The relationships of Saps activities and genotypes with S
      ECC were analyzed. The results showed that enzyme activities of Saps in the S-ECC
      group were significantly higher than those in the caries free (CF) group
      (p<0.05). Genotypes A, B and C were detected in the S-ECC group, and genotypes A
      and C were detected in the CF group. In the genotype A group, Saps activity in
      the S-ECC group was significantly different from that in the CF group (p<0.05).
      The gene expression level of Sap1 in the S-ECC group was significantly higher
      than that in the CF group (p=0.001), while Sap4 expression was significantly
      lower than that in the CF group (p=0.029). It can be concluded that Sap1-5 are
      the predominant proteinase genes expressed in C. albicans from dental biofilm and
      Sap1 may play an important role in the development of S-ECC.

PMID- 24933642
TI  - Methylene-linked anilide-bis(aryloxide) ligands: lithium, sodium, potassium,
      chromium(III), and vanadium(III) ligation.
AB  - The anilide-bis(aryloxide) proligands H3[ONO(R)] (where H3[ONO(R)] = 2,6-(3-R(1)
      5-R(2)-2-hydroxybenzyl)-4-tert-butyl-N-tolyl-aniline; H3[ONO(tBu)], R(1) = (t)Bu,
      R(2) = Me; H3[ONO(Me)], R(1) = Me, R(2) = (t)Bu; H3[ONO(Me2)], R(1) = R(2) = Me)
      were synthesized from 2-bromo-5-tert-butyl-isophthalic acid dimethyl ester in
      three steps in multigram scale. The ligand precursor H3[ONO(tBu)] was readily
      doubly and triply deprotonated with alkali metal reagents to generate the related
      derivatives M2[H(ONO(tBu))] and M3[ONO(tBu)] (M = Li, Na, K). The extent of
      ligand deprotonation is observed to depend on the choice of deprotonating
      reagents and solvents. Transmetalation reaction of the trilithium derivative
      Li3[ONO(tBu)] with MCl3(THF)3 (M = Cr, V; THF = tetrahydrofuran) afforded
      [(ONO(tBu))CrCl(THF){Li(THF)}] (5) and [(ONO(tBu))V(THF)] (6). The vanadium
      complex 6 reacted readily with 2-butyne, styrene oxide, and mesityl azide,
      yielding [(ONO(tBu))V(eta(2)-MeCCMe)] (7), [(ONO(tBu))V(O)] (8), and
      [(ONO(tBu))V(NMes)] (9), respectively. The solid-state structures of H3[ONO(tBu)]
      and metal complexes were determined by X-ray crystallography. The [ONO(tBu)]
      ligand adopts a u-shaped structure in solution and solid state. 

PMID- 24933641
TI  - An efficient Agrobacterium-mediated transformation system for poplar.
AB  - Poplar is a model system for the regeneration and genetic transformation of woody
      plants. To shorten the time required for studies of transgenic poplar, efforts
      have been made to optimize transformation methods that use Agrobacterium
      tumefaciens. In this study, an Agrobacterium infective suspension was treated at
      4  degrees C for at least 10 h before infecting explants. By transforming the
      Populus hybrid clone "Nanlin895" (Populus deltoides*P. euramericana) with
      Agrobacterium harboring the PBI121:CarNAC6 binary vector, we showed that the
      transformation efficiency was improved significantly by multiple independent
      factors, including an Agrobacterium infective suspension with an OD600 of 0.7, an
      Agrobacterium infection for 120 min, an Agrobacterium infective suspension at a
      pH of 5.0, an acetosyringone concentration of 200 uM, a cocultivation at 28 
      degrees C, a cocultivation for 72 h and a sucrose concentration of 30 g/L in the
      cocultivation medium. We also showed that preculture of wounded leaf explants for
      two days increased the regeneration rate. The integration of the desired gene
      into transgenic poplars was detected using selective medium containing kanamycin,
      followed by southern blot analysis. The expression of the transgene in the
      transgenic lines was confirmed by northern blot analysis.

PMID- 24933644
TI  - Ex vivo bubble production from ovine large blood vessels: size on detachment and
      evidence of "active spots".
AB  - Nanobubbles formed on the hydrophobic silicon wafer were shown to be the source
      of gas micronuclei from which bubbles evolved during decompression. Bubbles were
      also formed after decompression on the luminal surface of ovine blood vessels.
      Four ovine blood vessels: aorta, pulmonary vein, pulmonary artery, and superior
      vena cava, were compressed to 1013 kPa for 21 h. They were then decompressed,
      photographed at 1-s intervals, and bubble size was measured on detachment. There
      were certain spots at which bubbles appeared, either singly or in a cluster. Mean
      detachment diameter was between 0.7 and 1.0 mm. The finding of active spots at
      which bubbles nucleate is a new, hitherto unreported observation. It is possible
      that these are the hydrophobic spots at which bubbles nucleate, stabilise, and
      later transform into the gas micronuclei that grow into bubbles. The possible
      neurological effects of these large arterial bubbles should be further explored.

PMID- 24933643
TI  - Solution-phase parallel synthesis of acyclic nucleoside libraries of purine,
      pyrimidine, and triazole acetamides.
AB  - Molecular diversity plays a pivotal role in modern drug discovery against
      phenotypic or enzyme-based targets using high throughput screening technology.
      Under the auspices of the Pilot Scale Library Program of the NIH Roadmap
      Initiative, we produced and report herein a diverse library of 181 purine,
      pyrimidine, and 1,2,4-triazole-N-acetamide analogues which were prepared in a
      parallel high throughput solution-phase reaction format. A set of assorted amines
      were reacted with several nucleic acid N-acetic acids utilizing HATU as the
      coupling reagent to produce diverse acyclic nucleoside N-acetamide analogues.
      These reactions were performed using 24 well reaction blocks and an automatic
      reagent-dispensing platform under inert atmosphere. The targeted compounds were
      purified on an automated purification system using solid sample loading prepacked
      cartridges and prepacked silica gel columns. All compounds were characterized by
      NMR and HRMS, and were analyzed for purity by HPLC before submission to the
      Molecular Libraries Small Molecule Repository (MLSMR) at NIH. Initial screening
      through the Molecular Libraries Probe Production Centers Network (MLPCN) program,
      indicates that several analogues showed diverse and interesting biological
      activities. 

PMID- 24933646
TI  - N-terminal truncations of substance P 1-7 amide affect its action on spinal cord
      injury-induced mechanical allodynia in rats.
AB  - Central neuropathic pain can arise from injury of the spinal cord and can become
      chronic. Treatment is difficult and, because complete pain relief is currently
      very hard to achieve, there is a need for new, more effective treatment options.
      In this study we used an animal model of spinal cord injury to evaluate the
      potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating
      signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess
      antinociceptive properties. We also studied the effects of intraperitoneal
      injection of an amidated analog of this heptapeptide and of its truncated
      analogs, all of which had high affinity to the SP1-7 binding site, to evaluate
      the importance of the removed amino acids for the biodistribution and stability
      of the peptides. Most of the examined compounds alleviated mechanical allodynia
      without any signs of sedation or motor impairment in the rats. In contrast, the
      response threshold to acute nociceptive stimulation was not affected by any of
      the compounds tested. Most of the amino acids in the heptapeptide structure were
      essential for retaining the biological effect after peripheral injection. These
      observations suggest that the heptapeptide and its N-terminal truncated hexa- and
      pentapeptide analogs could be of interest for further development of analgesics
      in the management of mechanical allodynia. 

PMID- 24933645
TI  - Combination treatment of r-tPA and an optimized human apyrase reduces mortality
      rate and hemorrhagic transformation 6h after ischemic stroke in aged female rats.
AB  - Recombinant tissue plasminogen activator (r-tPA) is the only FDA-approved drug
      treatment for ischemic stroke and must be used within 4.5h. Thrombolytic
      treatment with r-tPA has deleterious effects on the neurovascular unit that
      substantially increases the risk of intracerebral hemorrhage if administered too
      late. These therapeutic shortcomings necessitate additional investigation into
      agents that can extend the therapeutic window for safe use of thrombolytics. In
      this study, combination of r-tPA and APT102, a novel form of human
      apyrase/ADPase, was investigated in a clinically-relevant aged-female rat embolic
      ischemic stroke model. We propose that successfully extending the therapeutic
      window of r-tPA administration would represent a significant advance in the
      treatment of ischemic stroke due to a significant increase in the number of
      patients eligible for treatment. Results of our study showed significantly
      reduced mortality from 47% with r-tPA alone to 16% with co-administration of
      APT102 and r-tPA. Co-administration decreased cortical (47 +/- 5% vs. 29 +/- 5%),
      striatal (50 +/- 2%, vs. 40 +/- 3%) and total (48 +/- 3%vs. 33 +/- 4%)
      hemispheric infarct volume compared to r-tPA alone. APT102 improved neurological
      outcome (8.9+/-0.6, vs. 6.8 +/- 0.8) and decreased hemoglobin extravasation in
      cortical tissue (1.9 +/- 0.1mg/dl vs. 1.4 +/- 0.1mg/dl) striatal tissue (2.1 +/-
      0.3mg/dl vs. 1.4 +/- 0.1mg/dl) and whole brain tissue (2.0 +/- 0.2mg/dl vs. 1.4
      +/- 0.1mg/dl). These data suggest that APT102 can safely extend the therapeutic
      window for r-tPA mediated reperfusion to 6h following experimental stroke without
      increased hemorrhagic transformation. APT102 offers to be a viable adjunct
      therapeutic option to increase the number of clinical patients eligible for
      thrombolytic treatment after ischemic stroke.

PMID- 24933647
TI  - Anti-cancer effects of ursane triterpenoid as a single agent and in combination
      with cisplatin in bladder cancer.
AB  - Ursolic acid and most of its derivatives are cytotoxic to bladder cancer cells.
      An ursolic acid derivative, isopropyl 3beta-hydroxyurs-12-en-28-oat (UA17),
      previously reported that it exhibited potent cytotoxicity against bladder cancer
      cells, NTUB1 cells. In this study, we further investigated the underlying
      mechanism of UA17 and evaluated its potential clinical use. UA17 may exert the
      onset of a p53-mediated p38 MAPK activation to up-regulate GADD153. GADD153, in
      turn, down-regulated Bcl-2 protein to cause mitochondrial membrane potential loss
      and apoptosis through intracellular ROS generation. In addition, UA17 markedly
      decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (CDK2 and
      CDK4), and caused increase of p21 and p27 levels. To assess the suitability of
      UA17 as a chemotherapeutic agent against NTUB1 cells, its cytotoxic effects have
      been further evaluated in the combination with cisplatin. The addition of UA17 to
      cisplatin induces possibly additive cell growth inhibition which correlated to
      the accumulation of S phase cells and a corresponding decrease in accumulation of
      G1 phase cells, accompanied an increased accumulation of sub-G1 phase cells.
      Furthermore, UA17/cisplatin combination exhibited increase of p21, cyclin E, and
      p-p53 level, and decrease of p27 and cyclin D1 proteins, and slightly diminishing
      the level of CDK2. P-p38 up-regulation induced by UA17/cisplatin combination
      through generation of ROS and Bcl-2 down-regulation induced by UA17/cisplatin
      combination increased cell death. Finally, the antitumorigenic effects of UA17 or
      UA17/cisplatin combination were further supported by their inhibition on growth
      of bladder tumor cells in a therapeutic murine MBT-2 bladder tumor model. 

PMID- 24933648
TI  - Gastric emptying is involved in Lactobacillus colonisation in mouse stomach.
AB  - Lactobacilli are indigenous microbes of the stomach of rodents, with much lower
      numbers being present in mice fed a purified diet than in those fed a non
      purified diet. We postulated that gastric emptying (GE) is responsible for the
      different colonisation levels of lactobacilli and tested this hypothesis in the
      present study. BALB/cCr Slc mice were fed either a non-purified diet or a
      purified diet for 2 weeks. The number of gastric tissue-associated lactobacilli
      was lower in mice fed the purified diet than in those fed the non-purified diet.
      GE, estimated by measuring the food recovered from the stomach, was higher in
      mice fed the purified diet than in those fed the non-purified diet and correlated
      negatively with the number of lactobacilli. Mice fed the non-purified diet
      exhibited lower GE rates even when lactobacilli were eliminated by ampicillin
      administration through the drinking-water, suggesting that GE is the cause but
      not the consequence of different Lactobacillus colonisation levels. The plasma
      concentrations of acylated ghrelin, a gastric hormone that promotes GE, were
      higher in mice fed the purified diet than in those fed the non-purified diet.
      There was a negative correlation between GE and the number of lactobacilli in
      mice fed the non-purified diet, the purified diet, and the purified diet
      supplemented with sugarbeet fibre (200 g/kg diet) or carboxymethyl cellulose (40
      g/kg diet). We propose that a higher GE rate contributes, at least in part, to
      lower gastric colonisation levels of lactobacilli in mice fed a purified diet.

PMID- 24933649
TI  - Simultaneous analysis of 22 volatile organic compounds in cigarette smoke using
      gas sampling bags for high-throughput solid-phase microextraction.
AB  - Quantifying volatile organic compounds (VOCs) in cigarette smoke is necessary to
      establish smoke-related exposure estimates and evaluate emerging products and
      potential reduced-exposure products. In response to this need, we developed an
      automated, multi-VOC quantification method for machine-generated, mainstream
      cigarette smoke using solid-phase microextraction gas chromatography-mass
      spectrometry (SPME-GC-MS). This method was developed to simultaneously quantify a
      broad range of smoke VOCs (i.e., carbonyls and volatiles, which historically have
      been measured by separate assays) for large exposure assessment studies. Our
      approach collects and maintains vapor-phase smoke in a gas sampling bag, where it
      is homogenized with isotopically labeled analogue internal standards and sampled
      using gas-phase SPME. High throughput is achieved by SPME automation using a CTC
      Analytics platform and custom bag tray. This method has successfully quantified
      22 structurally diverse VOCs (e.g., benzene and associated monoaromatics,
      aldehydes and ketones, furans, acrylonitrile, 1,3-butadiene, vinyl chloride, and
      nitromethane) in the microgram range in mainstream smoke from 1R5F and 3R4F
      research cigarettes smoked under ISO (Cambridge Filter or FTC) and Intense
      (Health Canada or Canadian Intense) conditions. Our results are comparable to
      previous studies with few exceptions. Method accuracy was evaluated with third
      party reference samples (<=15% error). Short-term diffusion losses from the gas
      sampling bag were minimal, with a 10% decrease in absolute response after 24 h.
      For most analytes, research cigarette inter- and intrarun precisions were <=20%
      relative standard deviation (RSD). This method provides an accurate and robust
      means to quantify VOCs in cigarette smoke spanning a range of yields that is
      sufficient to characterize smoke exposure estimates. 

PMID- 24933650
TI  - A royal college of radiologists national audit of radiotherapy in the treatment
      of metastatic spinal cord compression and implications for the development of
      acute oncology services.
AB  - AIMS: To audit the current use of radiotherapy in UK cancer centres for the
      treatment of metastatic spinal cord compression against national standards that
      seek to optimise functional and quality of life outcomes. MATERIALS AND METHODS:
      A Royal College of Radiologists prospective national audit of patients treated
      with radiotherapy in UK cancer centres was carried out over a 3 month period
      between September and December 2008, with a repeat audit carried out in August
      2012. RESULTS: Five hundred and ninety-six cases were received from 42 cancer
      centres (74%) in 2008, with data from 323 cases received from 52 (90%) centres in
      2012. Ninety-three per cent (358) of patients had a diagnostic magnetic resonance
      imaging scan carried out within 24 h of referral for radiotherapy in 2008
      compared with 205 patients (97%) in 2012. One hundred and eleven (32%) good
      prognosis patients were discussed with spinal surgeons; only 10 good prognosis
      patients were recorded as proceeding to surgery in 2008. This improved in 2012,
      with 94 (41% of good prognosis patients recorded as having been discussed with
      nine proceeding to surgery). Sixty-nine per cent of paraplegic patients in 2008
      received multiple fractions of radiotherapy, which was similar to 2012 when 62%
      received more than a single fraction. A metastatic spinal cord compression co
      ordinator was available in just over 50% of cases (164/323) and was involved in
      patient management in 26% of cases in 2012. CONCLUSION: Despite level 1 evidence
      of the superior functional outcome and survival benefit for surgery, few good
      prognosis patients were recorded as having been discussed with surgeons and even
      fewer proceeded to surgery.

PMID- 24933651
TI  - Differential patterns of effects of age and sex on metabolic syndrome in Taiwan:
      implication for the inadequate internal consistency of the current criteria.
AB  - AIMS: Current criteria of metabolic syndrome (MetS) give equal weight to each
      component and apply mostly the same cut-off values to all ages. The contribution
      of each component to MetS and the effects of age and sex on each component and
      MetS were explored. METHODS: We carried out a survey on residents aged 40-74
      years of the northern coastal area of Taiwan. The prevalent rates of MetS in 646
      males and 961 females were 32.4% and 27.8%, respectively. Logistic regression
      analyses were used to assess the main and interactive effects of age and sex. The
      Cronbach's alpha coefficient was calculated as the indicator of internal
      consistency of MetS components. RESULTS: There were significant age trends for
      MetS components, except for low HDL-C in both sexes and high fasting triglyceride
      in males. Logistic regression analyses showed that the effects of age and sex on
      MetS and its component were all different. The age-sex-specific Cronbach's alpha
      coefficients for MetS ranged from 0.43 to 0.61. The age trends of the
      coefficients in males and females were opposite. The exclusion of some components
      from the MetS resulted in an increase of the coefficients. CONCLUSIONS: Our
      results indicate that the internal consistency of MetS was questionable. It seems
      that the currently defined MetS components of MetS did not formulate a single
      pathophysiological entity. Given equal weight to each component and used the same
      cut-off values for the subjects of all age groups in both sexes need to be
      reconsidered.

PMID- 24933652
TI  - Psychiatric and substance-use comorbidities associated with lifetime crack
      cocaine use in young adults in the general population.
AB  - OBJECTIVE: To assess the association between lifetime crack cocaine use and
      psychiatric (post-traumatic stress disorder, current depression, current
      dysthymia, generalized anxiety disorder, panic disorder with agoraphobia, social
      phobia, as well as SRQ scores and suicide risk) and substance-use disorders
      (tobacco, alcohol, cannabis, cocaine, amphetamine, inhalants, sedatives,
      hallucinogens and opioids) in youth in the general population of the city of
      Pelotas, RS. METHOD: This was a cross-sectional population-based study, involving
      1560 participants between 18 and 24 ears old. Lifetime substance use and abuse
      were investigated using the ASSIST inventory. Psychiatric comorbidities were
      assessed using the Mini-International Neuropsychiatric Interview and symptoms of
      common mental disorders were evaluated with the Self-Reported Questionnaire
      (SRQ). RESULTS: The prevalence of lifetime crack cocaine use in the sample was
      2.5%. Its use was associated with total SRW scores and the presence of post
      traumatic stress disorder, antisocial personality disorder and suicide risk in
      the final regression model. Tobacco, alcohol, cannabis, cocaine, amphetamine and
      cocaine dependence were also associated with lifetime use of crack cocaine.
      DISCUSSION: Youth with a history of crack cocaine use had a higher prevalence of
      psychiatric conditions such as post-traumatic stress disorder, as well as an
      increased risk of tobacco, alcohol, cannabis, cocaine, amphetamine and inhalant
      use and dependence.

PMID- 24933653
TI  - A preliminary investigation of the effects of the unified protocol on
      temperament.
AB  - Previous research has shown that two dimensions of temperament referred to as
      neuroticism/behavioral inhibition (N/BI) and extraversion/behavioral activation
      (E/BA) are key risk factors in the development and maintenance of anxiety and
      mood disorders (Brown & Barlow, 2009). Given such findings, these temperamental
      dimensions may represent promising treatment targets for individuals with
      emotional disorders; however, to date, few studies have investigated the effects
      of psychological treatments on temperamental constructs generally assumed to be
      "stable, inflexible, and pervasive" (American Psychiatric Association, 2000). The
      present study addresses this gap in the literature by examining the effects of
      the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP;
      Barlow et al., 2011), a cognitive-behavioral therapy designed to target core
      processes of N/BI and E/BA temperaments, in a sample of adults with principal
      anxiety disorders and a range of comorbid conditions. Results revealed small
      effects of the UP on N/BI and E/BA compared with a waitlist control group at post
      treatment. Additionally, decreases in N/BI and increases in E/BA during treatment
      were associated with improvements in symptoms, functioning, and quality of life.
      Findings provide preliminary support for the notion that the UP treatment
      facilitates beneficial changes in dimensions of temperament. 

PMID- 24933655
TI  - Decrease in thermal conductivity in polymeric P3HT nanowires by size-reduction
      induced by crystal orientation: new approaches towards thermal transport
      engineering of organic materials.
AB  - To date, there is no experimental characterization of thermal conductivity of
      semiconductor polymeric individual nanowires embedded in a matrix. This work
      reports on scanning thermal microscopy measurements in a 3omega configuration to
      determine how the thermal conductivity of individual nanowires made of a model
      conjugated polymer (P3HT) is modified when decreasing their diameters. We observe
      a reduction of thermal conductivity, from lambdaNW = 2.29 +/- 0.15 W K(-1) m(-1)
      to lambdaNW = 0.5 +/- 0.24 W K(-1) m(-1), when the diameter of nanowires is
      reduced from 350 nm to 120 nm, which correlates with the polymer crystal
      orientation measured by WAXS. Through this work, the foundations for future
      polymer thermal transport engineering are presented. 

PMID- 24933654
TI  - Direct activation of ATM by resveratrol under oxidizing conditions.
AB  - Resveratrol has been widely reported to reduce cancer progression in model
      systems and to selectively induce cell death in transformed cell lines. Many
      enzymes have been reported to respond to resveratrol in mammalian cells,
      including the Ataxia-Telangiectasia Mutated (ATM) protein kinase that acts in DNA
      damage recognition, signaling, and repair. Here we investigate the responses of
      ATM to resveratrol exposure in normal and transformed human cell lines and find
      that ATM autophosphorylation and substrate phosphorylation is stimulated by
      resveratrol in a manner that is promoted by reactive oxygen species (ROS). We
      observe direct stimulatory effects of resveratrol on purified ATM in vitro and
      find that the catalytic efficiency of the kinase on a model substrate is
      increased by resveratrol. In the purified system we also observe a requirement
      for oxidation, as the effect of resveratrol on ATM signaling is substantially
      reduced by agents that prevent disulfide bond formation in ATM. These results
      demonstrate that resveratrol effects on ATM are direct, and suggest a mechanism
      by which the oxidizing environment of transformed cells promotes ATM activity and
      blocks cell proliferation. 

PMID- 24933656
TI  - Accurate determination of relative metatarsal protrusion with a small
      intermetatarsal angle: a novel simplified method.
AB  - Several published studies have explained in detail how to measure relative
      metatarsal protrusion on the plain film anteroposterior pedal radiograph. These
      studies have demonstrated the utility of relative metatarsal protrusion
      measurement in that it correlates with distal forefoot deformity or pathologic
      features. The method currently preferred by practitioners in podiatric medicine
      and surgery often presents one with the daunting challenge of obtaining an
      accurate measurement when the intermetatarsal 1-2 angle is small. The present
      study illustrates a novel mathematical solution to this problem that is simple to
      master, relatively quick to perform, and yields accurate results. Our method was
      tested and proven by 4 trained observers with varying degrees of clinical skill
      who independently measured the same 10 radiographs. 

PMID- 24933657
TI  - Highly infectious CJD particles lack prion protein but contain many viral-linked
      peptides by LC-MS/MS.
AB  - It is widely believed that host prion protein (PrP), without nucleic acid,
      converts itself into an infectious form (PrP-res) that causes transmissible
      encephalopathies (TSEs), such as human sporadic CJD (sCJD), endemic sheep
      scrapie, and epidemic BSE. There are many detailed investigations of PrP, but
      proteomic studies of other proteins in verified infectious TSE particles have not
      been pursued, even though brain homogenates without PrP retain their complete
      infectious titer. To define proteins that may be integral to, process, or protect
      an agent genome, we developed a streamlined, high-yield purification of
      infectious FU-CJD mouse brain particles with minimal PrP. Proteinase K (PK)
      abolished all residual particle PrP, but did not reduce infectivity, and viral
      size particles lacking PrP were ~70S (vs. 90-120S without PK). Furthermore, over
      1,500 non-PrP proteins were still present and positively identified in high titer
      FU-CJD particles without detectable PrP by mass spectrometry (LC-MS/MS); 114 of
      these peptides were linked to viral motifs in the environmental-viral database,
      and not evident in parallel uninfected controls. Host components were also
      identified in both PK and non-PK treated particles from FU-CJD mouse brain and
      human sCJD brain. This abundant cellular data had several surprises, including
      finding Huntingtin in the sCJD but not normal human brain samples. Similarly, the
      neural Wiskott-Aldrich sequence and multivesicular and endosome components
      associated with retromer APP (Alzheimer amyloid) processing were only in sCJD.
      These cellular findings suggest that new therapies directed at retromer-vesicular
      trafficking in other neurodegenerative diseases may also counteract late-onset
      sCJD PrP amyloid pathology.

PMID- 24933658
TI  - Poor outcome with nonmyeloablative conditioning regimen before cord blood
      transplantation for patients with high-risk acute myeloid leukemia compared with
      matched related or unrelated donor transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is recommended for
      patients with high-risk acute myeloid leukemia (AML). In many situations, a
      matched related (MRD) or matched unrelated donor (MUD) is lacking, in which case
      unrelated cord blood units (UCB) provide an alternative. We analyzed the outcome
      of consecutive high-risk AML patients prepared with reduced-intensity
      conditioning (RIC) regimens and allografted with UCB (n = 32) and compared their
      outcome with high-risk AML patients who underwent transplantation with MRD/MUD (n
      = 49) in the same period of time. Grade III to IV acute graft-versus-host disease
      (GVHD) occurred slightly more frequently in the UCB group (25%) than in the
      MRD/MUD group (8%) (P = .069). Conversely, we found a lower incidence of
      extensive chronic GVHD in the UCB group (6%) than in the MRD/MUD group (20%, P =
      .085). Nonrelapse mortality at 4 years was 16% and 22% in the UCB and MRD/MUD
      groups, respectively (P = .529). The cumulative incidence of relapse at 4 years
      was significantly higher in the UCB group (60%) than in the MRD/MUD group (27%, P
      = .006). Leukemia-free survival (LFS) and overall survival (OS) at 4 years were
      25% and 34%, respectively, in the UCB group and 50% and 56%, respectively, in the
      MRD/MUD group (LFS, P = .029; OS, P = .072). Multivariate analyses adjusted by
      cytogenetics and disease status at the time of Allo-HSCT revealed that use of UCB
      remained an independent predictive factor of shorter LFS (hazard ratio, 2.0; 95%
      confidence interval, 1.1 to 3.6; P = .018), and was associated with a trend for
      shorter OS (hazard ratio, 1.7; 95% confidence interval, .9 to 3.2; P = .093).
      Whereas UCB provides an alternative for patients with high-risk AML lacking an
      MRD/MUD, the high incidence of relapse after RIC-based UCB Allo-HSCT is a
      concern. Attempts to improve leukemic control with UCB Allo-HSCT are warranted,
      as well as the evaluation of other alternative donors in this context. 

PMID- 24933659
TI  - Quantification of the transverse carpal ligament elastic properties by sex and
      region.
AB  - BACKGROUND: The transverse carpal ligament is an integral factor in the etiology
      of carpal tunnel syndrome. The purpose of this study was to report the
      biomechanical properties of this ligament and quantify sex-based differences and
      regional variation in tissue response. We hypothesized that the mechanical
      response would not be uniform across the surface, and that female ligament
      properties would have higher strain profiles and lower mechanical properties.
      METHODS: Uniaxial testing of twelve (six males, six females) human fresh frozen
      cadaveric transverse carpal ligaments was carried out using an Instron Materials
      Testing Machine. Strain was measured via a non-contact optical method. FINDINGS:
      The following biomechanical properties of the transverse carpal ligament were
      reported in this work: failure strain (male: 9.2 (SD 5.0), female: 15.5 (SD
      7.1)%), strength (male: 4.9 (SD 1.5), female: 4.5 (SD 1.6) MPa), and modulus of
      elasticity (male: 52.9 (SD 19.6), female: 38.2 (SD 21.9) MPa). The radial side
      displayed significantly more strain at failure compared to ulnar (P<0.0001).
      INTERPRETATION: The results of this study provide evidence that manipulative
      treatments should focus stretching on the radial half of the tissue, which
      experiences larger strains under uniform loading conditions. In addition, this
      work suggests possible sex-based differences in mechanical properties of the
      transverse carpal ligament, which could provide a basis for the development of
      improved non-surgical treatment methods for carpal tunnel syndrome. The results
      can also be applied to generate more accurate computational models of the wrist.

PMID- 24933660
TI  - Risk of edge-loading and prosthesis impingement due to posterior pelvic tilting
      after total hip arthroplasty.
AB  - BACKGROUND: Proper implant orientation is essential for avoiding edge-loading and
      prosthesis impingement in total hip arthroplasty. Although cup orientation is
      affected by a change in pelvic tilt after surgery, it has been unclear whether
      surgeons can prevent impingement and edge-loading by proper positioning by taking
      into account any change in pelvic alignment associated with alteration of hip
      range of motion. METHODS: We simulated implant orientation without edge-loading
      and prosthesis impingement, even with a change in pelvic tilt and associated
      change in hip range of motion after surgery, by collision detection using implant
      models created with computer-aided design. FINDINGS: If posterior pelvic tilting
      with a corresponding hyperextension change in hip range of motion after surgery
      remains within 10 degrees , as occurs in 90% of cases, surgeons can avoid edge
      loading and impingement by correctly orienting the implant, even when using a
      conventional prosthesis. However, if a 20 degrees  change occurs after surgery,
      it may be difficult to avoid those risks. INTERPRETATION: Although edge-loading
      and impingement can be prevented by performing appropriate surgery in most cases,
      even when taking into account postoperative changes in pelvic tilt, it may also
      be important to pay attention to spinal conditions to ensure that pelvic tilting
      is not extreme because of increasing kyphosis.

PMID- 24933662
TI  - An ERP investigation of the co-development of hemispheric lateralization of face
      and word recognition.
AB  - The adult human brain would appear to have specialized and independent neural
      systems for the visual processing of words and faces. Extensive evidence has
      demonstrated greater selectivity for written words in the left over right
      hemisphere, and, conversely, greater selectivity for faces in the right over left
      hemisphere. This study examines the emergence of these complementary neural
      profiles, as well as the possible relationship between them. Using behavioral and
      neurophysiological measures, in adults, we observed the standard finding of
      greater accuracy and a larger N170 ERP component in the left over right
      hemisphere for words, and conversely, greater accuracy and a larger N170 in the
      right over the left hemisphere for faces. We also found that although children
      aged 7-12 years revealed the adult hemispheric pattern for words, they showed
      neither a behavioral nor a neural hemispheric superiority for faces. Of
      particular interest, the magnitude of their N170 for faces in the right
      hemisphere was related to that of the N170 for words in their left hemisphere.
      These findings suggest that the hemispheric organization of face recognition and
      of word recognition does not develop independently, and that word lateralization
      may precede and drive later face lateralization. A theoretical account for the
      findings, in which competition for visual representations unfolds over the course
      of development, is discussed.

PMID- 24933661
TI  - Contrasting networks for recognition memory and recency memory revealed by
      immediate-early gene imaging in the rat.
AB  - The expression of the immediate-early gene c-fos was used to compare networks of
      activity associated with recency memory (temporal order memory) and recognition
      memory. In Experiment 1, rats were first familiarized with sets of objects and
      then given pairs of different, familiar objects to explore. For the recency test
      group, each object in a pair was separated by 110 min in the time between their
      previous presentations. For the recency control test, each object in a pair was
      separated by less than a 1 min between their prior presentations. Temporal
      discrimination of the objects correlated with c-fos activity in the recency test
      group in several sites, including area Te2, the perirhinal cortex, lateral
      entorhinal cortex, as well as the dentate gyrus, hippocampal fields CA3 and CA1.
      For both the test and control conditions, network models were derived using
      structural equation modeling. The recency test model emphasized serial
      connections from the perirhinal cortex to lateral entorhinal cortex and then to
      the CA1 subfield. The recency control condition involved more parallel pathways,
      but again highlighted CA1 within the hippocampus. Both models contrasted with
      those derived from tests of object recognition (Experiment 2), because stimulus
      novelty was associated with pathways from the perirhinal cortex to lateral
      entorhinal cortex that then involved both the dentate gyrus (and CA3) and CA1 in
      parallel. The present findings implicate CA1 for the processing of familiar
      stimuli, including recency discriminations, while the dentate gyrus and CA3
      pathways are recruited when the perirhinal cortex signals novel stimuli.

PMID- 24933663
TI  - Verbal learning and memory in agenesis of the corpus callosum.
AB  - The role of interhemispheric interactions in the encoding, retention, and
      retrieval of verbal memory can be clarified by assessing individuals with
      complete or partial agenesis of the corpus callosum (AgCC), but who have normal
      intelligence. This study assessed verbal learning and memory in AgCC using the
      California Verbal Learning Test-Second Edition (CVLT-II). Twenty-six individuals
      with AgCC were compared to 24 matched controls on CVLT-II measures, as well as
      Donders' four CVLT-II factors (i.e., Attention Span, Learning Efficiency, Delayed
      Memory, and Inaccurate Memory). Individuals with AgCC performed significantly
      below healthy controls on the Delayed Memory factor, confirmed by significant
      deficits in short and long delayed free recall and cued recall. They also
      performed less well in original learning. Deficient performance by individuals
      with AgCC during learning trials, as well as deficits in all forms of delayed
      memory, suggest that the corpus callosum facilitates interhemispheric elaboration
      and encoding of verbal information. 

PMID- 24933664
TI  - Equity in surgical leadership for women: more work to do.
AB  - BACKGROUND: Sex disparity in the Program Director role has not been studied. The
      goal of this study is to evaluate the percentage of women in Chair and Program
      Director positions. We hypothesize that there is a higher percentage of women in
      the Program Director role than Chair role. METHODS: An Internet search identified
      Chairs, Program Directors, Associate Program Directors, and Division Chiefs.
      Statistical analysis compared percentages of women in these roles at all
      institutions, academic/community programs, and regions. RESULTS: There is higher
      female representation in the Program Director position than Chair position (P =
      .002) in General Surgery, Otolaryngology, and Orthopedics. More women are
      Associate Program Directors than Division Chiefs (23.6% vs 9.8%, P <= .001).
      Academic and community programs are no different. In the West, a greater
      percentage of women are Chairs as compared with the other regions (P <= .002).
      CONCLUSIONS: There are higher rates of women in Program Director position than
      Department Chair position. This discrepancy warrants further investigation.

PMID- 24933665
TI  - Outcomes of pancreatic debridement in acute pancreatitis: analysis of the
      nationwide inpatient sample from 1998 to 2010.
AB  - BACKGROUND: The objective of this study was to perform a national review of
      patients with acute pancreatitis (AP) who undergo pancreatic debridement (PD) to
      evaluate for risk factors of in-hospital mortality. METHODS: The Nationwide
      Inpatient Sample was used to identify patients with AP who underwent PD between
      1998 and 2010. Risk factors for in-hospital mortality were assessed with
      multivariate logistic regression. RESULTS: From 1998 to 2010, there were 585,978
      nonelective admissions with AP, of which 1,783 (.3%) underwent PD. From 1998 to
      2010, the incidence of PD decreased from .44% to .25% (P < .01) and PD in
      hospital mortality decreased from 29.0% to 15% (P < .05). Of patients undergoing
      PD, independent factors associated with increased odds of mortality were
      increased age (odds ratio [OR] 1.04, confidence interval [CI] 1.03 to 1.05; P <
      .01), sepsis with organ failure (OR 1.76, CI 1.24 to 2.51; P < .01), peptic ulcer
      disease (OR 1.83, CI 1.02 to 3.30; P < .05), liver disease (OR 2.27, CI 1.36 to
      3.78; P < .01), and renal insufficiency (OR 1.78, CI 1.14 to 2.78; P < .05).
      CONCLUSIONS: The incidence and operative mortality of PD have decreased
      significantly over the last decade in the United States with higher odds of dying
      in patients who are older, with chronic liver, renal, or ulcer disease, and
      higher rates of sepsis with organ failure.

PMID- 24933666
TI  - The eye of the master.

PMID- 24933667
TI  - The use of rapid thromboelastogram for trauma mortality prediction.

PMID- 24933668
TI  - Can trauma surgeons manage mild traumatic brain injuries?
AB  - BACKGROUND: Current practices suggest that patients with mild traumatic brain
      injuries (MTBI) receive neurosurgical consultations, while less than 1% require
      neurosurgical intervention. We implemented a policy of selective neurosurgical
      consultation with the hypothesis that trauma surgeons alone may manage such
      patients with no impact on patient outcomes. METHODS: Data from a level I trauma
      registry were analyzed. Patients with MTBI resulting in an intracranial
      hemorrhage of 1 cm or less and a Glasgow Coma Score of 13 or greater were
      included. Patients with additional intracranial injuries were excluded.
      Multivariate regression was used to determine the relationship between
      neurosurgical management and good neurologic outcomes, while controlling for
      injury severity, demographics, and comorbidities. RESULTS: Implementation of the
      neurosurgical policy significantly reduced the number of such consults (94%
      before vs 65% after, P < .002). Multivariate analysis revealed that neurosurgical
      consultation was not associated with neurologic outcomes of patients.
      CONCLUSIONS: Implementation of a selective neurosurgical consultation policy for
      patients with MTBI reduced neurosurgical consultations without any impact on
      patient outcomes, suggesting that trauma surgeons can effectively manage these
      patients.

PMID- 24933669
TI  - Large and complex ventral hernia repair using "components separation technique"
      without mesh results in a high recurrence rate.
AB  - BACKGROUND: Recurrence rates after component separation technique (CST) are low
      in the literature but may be underestimated because of inadequate follow-up
      methods. METHODS: Prospective patient follow-up was performed of consecutive
      patients who underwent repair of large and complex ventral hernias using CST
      without mesh utilization. Primary outcome was recurrent hernia determined by
      clinical examination at least 1 year after surgery in all living patients.
      Current literature underwent meta-analysis regarding outcomes and mode of follow
      up. RESULTS: Seventy-five patients were included with a mean age of 52.2 years
      and a mean defect size of 214.9 cm(2), respectively. Twenty-nine patients (38.7%)
      had a recurrent hernia after a mean of 40.9-month follow-up, and this was
      significantly higher than in the literature (14.0%, P < .01). Sixty-four percent
      of studies in the literature were unclear about the method of determining
      recurrent hernia or included telephone follow-up and questionnaires. CONCLUSIONS:
      CST coincides with a high recurrence rate when clinical follow-up is longer than
      a year. Reported recurrence rates are probably underestimated because the method
      and duration of follow-up are inadequate.

PMID- 24933670
TI  - How prepared are your interns to take calls? Results of a multi-institutional
      study of simulated pages to prepare medical students for surgery internship.
AB  - BACKGROUND: This study evaluated a simulated pages curriculum that was developed
      to assess communication and clinical decision making in medical students and
      interns. METHODS: A curriculum consisting of 14 simulated pages was administered
      across 5 institutions to 150 senior medical students. A 3-case subset was
      administered to interns who did not participate in the curriculum. Six expert
      surgeons identified critical fails and set passing scores for case-specific
      assessments using the Graphical Hofstee Method. RESULTS: Participants in the
      curriculum demonstrated superior clinical decision making compared with non
      participants across all cases scenarios (P < .01). Average medical student scores
      for clinical decision making were 46.9%. Global ratings averaged 6.0 for
      communication and 5.2 for patient care. Passing rates averaged 46%. CONCLUSIONS:
      Participation in a mock page curriculum improved performance. The performance of
      participants based on expert standards set for simulated page performance
      highlight the need for innovative approaches to improve interns' preparedness to
      take calls.

PMID- 24933671
TI  - [Post anoxia impairment of autobiographical memory and time estimation].
AB  - A case of episodic amnesia with impairment of time perception is described; it
      illustrates the link between time perception and autobiographical memory. This
      woman suffered from a Sheehan syndrome with anoxia at the age of 36 and since
      that date has had a strong and isolated difficulty to estimate the date and
      duration of events in a range of weeks, months or years. Conversely, short
      duration time spans are correctly evaluated. The patient's complaints also
      involve episodic memory. She reports many events from her biography very
      imprecisely while the semantic autobiographical data are preserved. The patient
      has difficulty in recalling the date of public events and the period of celebrity
      of well-known people. That observation confirms the specificity of time
      organization for long periods and the link with the episodic memory where the
      context of the dating task is crucial. The results are discussed in reference to
      autobiographical memory that involves mental wandering in time-space and the
      constitution of self over a time continuum. 

PMID- 24933672
TI  - [Recurrent painful ophthalmoplegic neuropathy or recurrent demyelinating
      neuropathy].

PMID- 24933673
TI  - Preparation of TiO2 nanoparticles coated with ionic liquids: a supramolecular
      approach.
AB  - Coated TiO2 nanoparticles by dicationic imidazolium-based ionic liquids (ILs)
      were prepared and studied by differential scanning calorimetry (DSC), dynamic
      light scattering (DLS), transmission electron microscopy (TEM), powder X-ray
      diffraction (XRD), and scanning electron microscopy (SEM). Three ILs with
      different hydrophobicity degrees and structural characteristics were used (IL-1,
      IL-2, and IL-3). The interaction between IL molecules and the TiO2 surface was
      analyzed in both solid state and in solution. The physical and chemical
      properties of coated nanoparticles (TiO2 + IL-1, TiO2 + IL-2, and TiO2 + IL-3)
      were compared to pure materials (TiO2, IL-1, IL-2, and IL-3) in order to evaluate
      the interaction between both components. Thermal behavior, diffraction pattern,
      and morphologic characteristics were evaluated in the solid state. It was
      observed that all mixtures (TiO2 + IL) showed different behavior from that
      detected for pure substances, which is an evidence of film formation. DLS
      experiments were conducted to determine film thickness on the TiO2 surface
      comparing the size (hydrodynamic radius, Rh) of pure TiO2 with coated
      nanoparticles (TiO2 + IL). Results showed the thickness of the film increased
      with hydrophobicity of the IL compound. TEM images support this observation.
      Finally, X-ray diffraction patterns showed that, in coated samples, no structural
      changes in TiO2 diffraction peaks were observed, which is related to the
      maintenance of the crystalline structure. On the contrary, ILs showed different
      diffraction patterns, which confirms the hypothesis of interactions happening
      between IL and the TiO2 nanoparticles surface. 

PMID- 24933674
TI  - Surgical emergencies in oncology.
AB  - An oncologic emergency is defined as an acute, potentially life threatening
      condition in a cancer patient that has developed as a result of the malignant
      disease or its treatment. Many oncologic emergencies are signs of advanced, end
      stage malignant disease. Oncologic emergencies can be divided into medical or
      surgical. The literature was reviewed to construct a summary of potential
      surgical emergencies in oncology that any surgeon can be confronted with in daily
      practice, and to offer insight into the current approach for these wide ranged
      emergencies. Cancer patients can experience symptoms of obstruction of different
      structures and various causes. Obstruction of the gastrointestinal tract is the
      most frequent condition seen in surgical practice. Further surgical emergencies
      include infections due to immune deficiency, perforation of the gastrointestinal
      tract, bleeding events, and pathological fractures. For the institution of the
      appropriate treatment for any emergency, it is important to determine the
      underlying cause, since emergencies can be either benign or malignant of origin.
      Some emergencies are well managed with conservative or non-invasive treatment,
      whereas others require emergency surgery. The patient's performance status,
      cancer stage and prognosis, type and severity of the emergency, and the patient's
      wishes regarding invasiveness of treatment are essential during the decision
      making process for optimal management. 

PMID- 24933675
TI  - Asymmetric synthesis of substituted NH-piperidines from chiral amines.
AB  - Previously, we reported an efficient asymmetric synthesis of substituted
      piperidines through an exocyclic chirality induced nitroalkene/amine/enone (NAE)
      condensation reaction. An effective protecting group strategy was developed
      herein to achieve enantiopure piperidines (yields up to 92%) with complete
      chirality retention (ee > 95%). A simple derivatization of the obtained
      piperidines gave thiourea catalysts, indicating the strong potential of this
      method for producing new amine-based dual functional organocatalysts for future
      development. 

PMID- 24933676
TI  - Patients surviving six months in hospice care: who are they?
AB  - BACKGROUND: On January 1, 2011, the Centers for Medicare and Medicaid Services
      (CMS) began requiring U.S. hospices to conduct a "face-to-face" (F2F) assessment
      of eligibility for continued hospice care with patients entering their third
      certification period (180 days after initial enrollment). Understanding which
      patient populations require F2F assessment is important for evaluating the impact
      of the CMS regulation and gauging the appropriateness of the 6-month prognosis
      criteria for different patient groups. METHODS: Retrospective program records
      were obtained for patients enrolled in a large hospice 6 months prior to
      implementation of the CMS regulation (N=375). Patients who remained in hospice
      and received a F2F (n=140) were compared to patients who were no longer in
      hospice (n=235) on demographics, terminal condition (categorized as
      debility/dementia, cancer, or other), presence of serious comorbidity, length of
      stay, setting of care prior to admission, and hospice outcome using bivariate
      statistics. Predictors of F2F recertification were examined using a multivariable
      logistic regression model controlling for demographics, setting of care prior to
      admission, comorbidity, and primary terminal diagnosis. RESULTS: At the bivariate
      level, patients who received an F2F were older (p<0.001), and more likely to have
      lived in a facility care setting prior to hospice admission (p<0.001) than their
      non-F2F counterparts. Findings from the logistic regression analysis indicate
      that initial setting of care (odds ratio [OR] for inpatient versus home=0.20;
      p=0.01), presence of serious comorbidity (OR=2.84; p<0.001), and primary
      diagnosis (OR for debility/dementia versus cancer=3.35; p<0.001) were significant
      predictors of F2F recertification. CONCLUSIONS: Unlike hospice patients with
      cancer, patients with a primary diagnosis of dementia or debility are more likely
      to remain in hospice care beyond 6 months and require F2F recertification. Still,
      these patients need the services provided by hospice care and may be limited by
      the 6-month recertification criteria.

PMID- 24933677
TI  - So much hope for lupus, at last.

PMID- 24933678
TI  - When biologics should be used in systemic lupus erythematosus?
AB  - Recently, the use and evaluation of biologics increased in systemic lupus
      erythematosus (SLE). However, no international recommendation is available
      concerning the use of biologics with regards to the subset of patients who should
      be treated, the optimal time to treat, the objective of treatment and the manner
      to discontinue it. To address these complex questions, we focused on biologics
      already evaluated in at least two published randomized controlled trials. We
      summarized the results of these trials and available observational data in
      registries. Taking into account the clinical evidence, we proposed some guidance
      on the way biologics could be used in SLE. Many areas of uncertainty persist and
      require intensifying efforts from the academic world to set up new trials, and
      develop international recommendations. 

PMID- 24933679
TI  - [Long-term mechanical circulatory support in 2014: A real alternative to heart
      transplantation?].
AB  - Cardiac transplantation remains the gold standard for end stage heart failure
      however results of long-term mechanical circulatory support have dramatically
      improved over the last 10years. One should now clearly consider a left
      ventricular assist device as bridge to transplant or destination therapy in
      refractory isolated left heart failure. Mechanical biventricular support remains
      more challenging with lower survival and may be proposed as bridge to transplant.
      Correct patient's selection and appropriate follow-up are mandatory in such
      critical patients. 

PMID- 24933680
TI  - [Early diagnosis of Alzheimer's disease: are we too close to the trees to see the
      forest?].

PMID- 24933681
TI  - Enhanced catalytic efficiency in quercetin-4'-glucoside hydrolysis of Thermotoga
      maritima beta-glucosidase A by site-directed mutagenesis.
AB  - Te-BglA and Tm-BglA are glycoside hydrolase family 1 beta-glucosidases from
      Thermoanaerobacter ethanolicus JW200 and Thermotoga maritima, respectively, with
      53% sequence identity. However, Te-BglA could more effectively hydrolyze
      isoflavone glucosides to their aglycones than could Tm-BglA, possibly due to the
      difference in amino acid residues around their glycone binding pockets. Site
      directed mutagenesis was used to replace the amino acid residues of Tm-BglA with
      the corresponding residues of Te-BglA, generating three single mutants (F221L,
      N223L, and G224T), as well as the corresponding three double mutants
      (F221L/N223L, F221L/G224T, and N223L/G224T) and one triple mutant
      (F221L/N223L/G224T). The seven mutants have been purified, characterized, and
      compared to the wild-type Tm-BglA. The effects of the mutations on kinetics,
      enzyme activity, and substrate specificity were determined. All mutants showed pH
      activity curves narrower on the basic side and wider on the acid side and had
      similar optimal pH and stability at pH 6.5-8.3. They were more stable up to 85 
      degrees C, but G224T displayed higher optimal temperature than Tm-BglA. Seven
      mutants indicated an obvious increase in catalytic efficiency toward p
      nitrophenyl beta-D-glucopyranoside (pNPG) but an increase or not change in K(m).
      All mutants showed a decrease in catalytic efficiency of isoflavonoid glycosides
      and were not changed for F221L and lost for N223L in enzymatic hydrolysis on
      quercetin glucosides. Contrarily, G224T resulted in a dramatic increase
      conversion of Q4' (35.5%) and Q3,4' (28.6%) in accord with an increased turnover
      number (k(cat), 1.4*) and catalytic efficiency (k(cat)/K(m), 2.2*) as well as a
      decrease in K(m) (0.24) for Q4'. Modeling showed that G224T mutation at position
      224 may enhance the interaction between G224T and 5-OH and 3-OH on the quercetin
      backbone of Q4'.

PMID- 24933682
TI  - Raman and coherent anti-Stokes Raman scattering microscopy studies of changes in
      lipid content and composition in hormone-treated breast and prostate cancer
      cells.
AB  - Increasing interest in the role of lipids in cancer cell proliferation and
      resistance to drug therapies has motivated the need to develop better tools for
      cellular lipid analysis. Quantification of lipids in cells is typically done by
      destructive chromatography protocols that do not provide spatial information on
      lipid distribution and prevent dynamic live cell studies. Methods that allow the
      analysis of lipid content in live cells are therefore of great importance. Using
      micro-Raman spectroscopy and coherent anti-Stokes Raman scattering (CARS)
      microscopy, we generated a lipid profile for breast (T47D, MDA-MB-231) and
      prostate (LNCaP, PC3) cancer cells upon exposure to medroxyprogesterone acetate
      (MPA) and synthetic androgen R1881. Combining Raman spectra with CARS imaging, we
      can study the process of hormone-mediated lipogenesis. Our results show that
      hormone-treated cancer cells T47D and LNCaP have an increased number and size of
      intracellular lipid droplets and higher degree of saturation than untreated
      cells. MDA-MB-231 and PC3 cancer cells showed no significant changes upon
      treatment. Principal component analysis with linear discriminant analysis of the
      Raman spectra was able to differentiate between cancer cells that were treated
      with MPA, R1881, and untreated.

PMID- 24933684
TI  - Balancing safety and enjoyment. Current practice when recommending tastes for
      people with intellectual disabilities who are non-orally fed.
AB  - Eating and drinking problems are common among people with intellectual
      disabilities. Having a compromised swallow or being at risk of inadequate
      nutrition are two reasons for introducing non-oral feeding. Such procedures
      involve the creation of an external opening for food and drink to be delivered
      directly into the stomach through a tube. In recent years maintenance of the
      swallow and quality of life issues have led to introduction of small amounts of
      food and drink (oral tastes) for people who are non-orally fed. Little evidence
      exists about the reasoning used to inform this decision or the types of oral
      tastes offered. This study aims to address these omissions. An exploratory
      survey, distributed via email, was used to gather information from speech and
      language therapists and dietitians about their current practice and their
      decision-making processes when offering oral tastes to people who are non-orally
      fed. Data presented here reflect the responses from respondents working primarily
      with people with intellectual disabilities (55 out of 158 respondents). Oral
      tastes were being offered and clinical decision-making around this centred on
      balancing the wellbeing and wishes of the person with intellectual disabilities
      and their carers with the risks to wellbeing inherent in implementing and
      supporting an oral taste programme. 

PMID- 24933683
TI  - Development of Raman spectral markers to assess metastatic bone in breast cancer.
AB  - Bone is the most common site for breast cancer metastases. One of the major
      complications of bone metastasis is pathological bone fracture caused by chronic
      bone loss and degeneration. Current guidelines for the prediction of pathological
      fracture mainly rely on radiographs or computed tomography, which are limited in
      their ability to predict fracture risk. The present study explored the
      feasibility of using Raman spectroscopy to estimate pathological fracture risk by
      characterizing the alterations in the compositional properties of metastatic
      bones. Tibiae with evident bone destruction were investigated using Raman
      spectroscopy. The carbonation level calculated by the ratio of
      carbonate/phosphate nu1 significantly increased in the tumor-bearing bone at all
      the sampling regions at the proximal metaphysis and diaphysis, while tumor
      induced elevation in mineralization and crystallinity was more pronounced in the
      metaphysis. Furthermore, the increased carbonation level is positively correlated
      to bone lesion size, indicating that this parameter could serve as a unique
      spectral marker for tumor progression and bone loss. With the promising advances
      in the development of spatially offset Raman spectroscopy for deep tissue
      measurement, this spectral marker can potentially be used for future noninvasive
      evaluation of metastatic bone and prediction of pathological fracture risk.

PMID- 24933685
TI  - Adjusting to motherhood. The importance of BMI in predicting maternal well-being,
      eating behaviour and feeding practice within a cross cultural setting.
AB  - Maternal body mass index (BMI) is associated with negative body image and
      restrained eating which are experienced differently across cultures. The present
      study aimed to: 1) examine if self-esteem, eating behaviours and body
      satisfaction changed from early pregnancy to 2-6 months after giving birth; 2)
      explore changes according to country (Israel vs. UK) and BMI; and 3) determine
      any relationship between these measurements and infant feeding. Participants
      completed questionnaires assessing self-esteem, body image and eating/feeding
      behaviours. Multilevel linear modelling was used to account for change and to
      assess the independent impact of BMI on outcomes. Seventy-three women and infants
      participated in the study in early pregnancy and again 16 (9) weeks following
      birth. Women gained 1.5 kg (range -12 + 23) and UK mothers reported significantly
      greater body dissatisfaction, but self-esteem and eating behaviours remained
      stable. BMI was the main predictor of self-esteem, eating behaviours and body
      satisfaction. Mothers' perceptions of infant's eating did not vary according to
      BMI or country; however, heavier mothers reported feeding their infants according
      to a schedule. The first months after giving birth are a key time to assess
      adjustment to motherhood but later assessments are necessary in order to track
      changes beyond the early period post-pregnancy. 

PMID- 24933686
TI  - Scents boost preference for novel fruits.
AB  - When faced with a novel food, multisensory information that includes appearance
      and smell is a very important cue for preference, categorization, and the
      decision of whether or not to eat it. We elucidated whether olfactory information
      leads to biased visual categorization of and preference for fruits, even when
      odors are presented subliminally. We employed morphed images of strawberries and
      tomatoes combined with their corresponding odorants as stimuli. Participants were
      asked to categorize the images into either of two categories, to evaluate their
      preference for each visual image, and to judge the presence/absence of the odor.
      Results demonstrated that visual categorization was not affected by the odor
      manipulation; however, preference for uncategorizable images increased when odors
      were presented regardless of the participant's awareness of the odor. Our
      findings suggest that visual preference for novel fruits is based on both
      conscious and unconscious olfactory processing regarding edibility. 

PMID- 24933687
TI  - Tailoring the electronic structure in bilayer molybdenum disulfide via interlayer
      twist.
AB  - Molybdenum disulfide bilayers with well-defined interlayer twist angle were
      constructed by stacking single-crystal monolayers. Varying interlayer twist angle
      results in strong tuning of the indirect optical transition energy and second
      harmonic generation and weak tuning of direct optical transition energies and
      Raman mode frequencies. Electronic structure calculations show the interlayer
      separation changes with twist due to repulsion between sulfur atoms, resulting in
      shifts of the indirect optical transition energies. These results show that
      interlayer alignment is a crucial variable in tailoring the properties of two
      dimensional heterostructures. 

PMID- 24933688
TI  - Long-term deficits in quadriceps strength and activation following anterior
      cruciate ligament reconstruction.
AB  - OBJECTIVE: Even some time after a ruptured ACL has been reconstructed thigh
      musculature atrophy, voluntary activation, and knee-extensor strength deficits
      may be encountered. The purpose of this study was to evaluate bilateral knee
      extension strength, voluntary activation of the quadriceps, and thigh
      circumference in males and females with ACL reconstruction (ACLR). DESIGN AND
      PARTICIPANTS: Within-subject and between-subject designs were used to evaluate 24
      unilateral ACLR individuals and 23 controls. MAIN OUTCOME MEASURES: Isokinetic
      knee-extension strength was assessed in ACLR participants while central
      activation ratio (CAR) and thigh circumference measures were obtained from both
      groups. RESULTS: Knee-extensor strength deficits (p < .039) and lower CAR of the
      quadriceps were found in the ACLR limb compared to the uninvolved limb (p =
      .047). Extensor strength was greater in males (p < .001), however, CAR was not
      different between sexes (p = .086). No difference in voluntary activation was
      revealed among the ACLR limb, uninvolved limb, and control limb when compared as
      independent groups (p = .460). The strength deficits found in the ACLR limb are
      partly attributable to lower voluntary activation compared to the uninvolved leg,
      given that no difference was found in thigh circumference between legs.
      CONCLUSION: Clinicians should consider the deficits in muscle function when
      returning patients to pre-injury activity levels.

PMID- 24933689
TI  - Discovery, isolation, and structure elucidation of dretamycin.
AB  - The Candida albicans fitness test is a whole cell screening platform that
      utilizes a mixed-pool of C. albicans mutants, each of which carries a
      heterozygous deletion of a particular gene. In the presence of an antifungal
      inhibitor, a subset of these mutants exhibits a growth phenotype of
      hypersensitivity or hyposensitivity. Collectively these mutants reflect aspects
      of the mechanism of action of the compound in question. In the course of
      screening natural products a culture of Streptomyces sp. MS-1-4 was discovered to
      produce a compound, dretamycin, which yielded a fitness profile exhibiting
      significant hypersensitivity of the DRE2 heterozygote and hyposensitivity of the
      DIP5 heterozygote. Herein we report the production, isolation, and structure
      elucidation of dretamycin. 

PMID- 24933690
TI  - Exploring the heterologous genomic space for building, stepwise, complex,
      multicomponent tolerance to toxic chemicals.
AB  - Modern bioprocessing depends on superior cellular traits, many stemming from
      unknown genes and gene interactions. Tolerance to toxic chemicals is such an
      industrially important complex trait, which frequently limits the economic
      feasibility of producing commodity chemicals and biofuels. Chemical tolerance
      encompasses both improved cell viability and growth under chemical stress.
      Building upon the success of our recently reported semisynthetic stress response
      system expressed off plasmid pHSP (Heat Shock Protein), we probed the genomic
      space of the solvent tolerant Lactobacillus plantarum to identify genetic
      determinants that impart solvent tolerance in combination with pHSP. Using two
      targeted enrichments, one for superior viability and one for better growth under
      ethanol stress, we identified several beneficial heterologous DNA determinants
      that act synergistically with pHSP. In separate strains, a 209% improvement in
      survival and an 83% improvement in growth over previously engineered strains
      based on pHSP were thus generated. We then developed a composite phenotype of
      improved growth and survival by combining the identified L. plantarum genetic
      fragments. This demonstrates the concept for a sequential, iterative assembly
      strategy for building multigenic traits by exploring the synergistic effects of
      genetic determinants from a much broader genomic space. The best performing
      strain produced a 3.7-fold improved survival under 8% ethanol stress, as well as
      a 32% increase in growth under 4% ethanol. This strain also shows significantly
      improved tolerance to n-butanol. Improved solvent production is rarely examined
      in tolerance engineering studies. Here, we show that our system significantly
      improves ethanol productivity in a Melle-Boinot-like fermentation process. 

PMID- 24933692
TI  - Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory
      diseases.
AB  - It is well established that glial cells have critical roles in the inflammatory
      processes in the central nervous system (CNS). These cells can be activated by a
      variety of endogenous and exogenous stimuli (i.e. gliosis) and can produce high
      levels of bioactive compounds that are noxious for neuronal cell function. One of
      the most important molecules released by activated glial cells is the bioactive
      free radical nitric oxide (NO). Although NO physiologically acts as both
      neuromodulator and neurotransmitter in the brain, excess production of NO by
      glial cells has diverse harmful effects on neuronal function, causing neuronal
      cell injury/death. The production of NO is induced by overexpression of the
      inducible isoform of NO synthase (iNOS) enzyme in glial cells. In this review, we
      describe the possible mechanisms that underlie the iNOS-mediated overproduction
      of glial NO in several pediatric and adult neuropathologic conditions such as
      periventricular leukomalacia (PVL), Krabbe's disease, X-linked
      adrenoleukodystrophy (ALD) and multiple sclerosis (MS). We specifically discuss
      various signaling cascades that activate several transcription factors involved
      in the iNOS expression in both astrocytes and microglia. We also discuss the
      consequences of iNOS-mediated NO production in neuroinflammatory diseases
      including MS. A complete understanding of the regulation of iNOS expression in
      glial cells and the mechanisms by which iNOS-mediated NO production is involved
      in neuroinflammation can provide new insights into the identification of novel
      targets for therapeutic intervention in NO-mediated neurologic diseases. 

PMID- 24933691
TI  - The role of matrix in HIV-1 envelope glycoprotein incorporation.
AB  - Incorporation of the viral envelope (Env) glycoprotein is a critical requirement
      for the production of infectious HIV-1 particles. It has long been appreciated
      that the matrix (MA) domain of the Gag polyprotein and the cytoplasmic tail of
      Env are central players in the process of Env incorporation, but the precise
      mechanisms have been elusive. Several recent developments have thrown light on
      the contributions of both proteins, prompting a re-evaluation of the role of MA
      during Env incorporation. The two domains appear to play distinct but
      complementary roles, with the cytoplasmic tail of Env responsible for directing
      Env to the site of assembly and the matrix domain accommodating the cytoplasmic
      tail of Env in the Gag lattice. 

PMID- 24933694
TI  - Yielding to desire: the durability of affective preferences.
AB  - People's expectations about the future are guided not just by the contingencies
      of situations but also by what they hope or wish will happen next. These
      preferences can inform predictions that run counter to what should or must occur
      based on the logic of unfolding events. Effects of this type have been regularly
      identified in studies of judgment and decision making, with individuals' choices
      often reflecting emotional rather than rational influences. Encouraging
      individuals to rely less on their emotional considerations has proven a challenge
      as affective responses are generated quickly and are seemingly informative for
      decisions. In 6 experiments we examined whether individuals could be encouraged
      to rely less on their affective preferences when making judgments about future
      events. Participants read stories in which contexts informed the likelihood of
      events in ways that might run counter to their preferential investments in
      particular outcomes. While being less than relevant given the logic of events,
      participants' affective considerations remained influential despite time allotted
      for predictive reflection. In contrast, instructional warnings helped attenuate
      the influence of affective considerations, even under conditions previously shown
      to encourage preferential biases. The findings are discussed with respect to
      factors that mediate preference effects, and highlight challenges for overcoming
      people's reliance on affective contributors to everyday judgments and
      comprehension.

PMID- 24933695
TI  - Why do participants initiate free recall of short lists of words with the first
      list item? Toward a general episodic memory explanation.
AB  - Participants who are presented with a short list of words for immediate free
      recall (IFR) show a strong tendency to initiate their recall with the 1st list
      item and then proceed in forward serial order. We report 2 experiments that
      examined whether this tendency was underpinned by a short-term memory store, of
      the type that is argued by some to underpin recency effects in IFR. In Experiment
      1, we presented 3 groups of participants with lists of between 2 and 12 words for
      IFR, delayed free recall, and continuous-distractor free recall. The to-be
      remembered words were simultaneously spoken and presented visually, and the
      distractor task involved silently solving a series of self-paced, visually
      presented mathematical equations (e.g., 3 + 2 + 4 = ?). The tendency to initiate
      recall at the start of short lists was greatest in IFR but was also present in
      the 2 other recall conditions. This finding was replicated in Experiment 2, where
      the to-be-remembered items were presented visually in silence and the
      participants spoke aloud their answers to computer-paced mathematical equations.
      Our results necessitate that a short-term buffer cannot be fully responsible for
      the tendency to initiate recall from the beginning of a short list; rather, they
      suggest that the tendency represents a general property of episodic memory that
      occurs across a range of time scales.

PMID- 24933693
TI  - The changeable nervous system: studies on neuroplasticity in cerebellar cultures.
AB  - Circuit reorganization after injury was studied in a cerebellar culture model.
      When cerebellar cultures derived from newborn mice were exposed at explantation
      to a preparation of cytosine arabinoside that destroyed granule cells and
      oligodendrocytes and compromised astrocytes, Purkinje cells surviving in greater
      than usual numbers were unensheathed by astrocytic processes and received twice
      the control number of inhibitory axosomatic synapses. Purkinje cell axon
      collaterals sprouted and many of their terminals formed heterotypical synapses
      with other Purkinje cell dendritic spines. The resulting circuit reorganization
      preserved inhibition in the cerebellar cortex. Following this reorganization,
      replacement of the missing granule cells and glia was followed by a restitution
      of the normal circuitry. Most of these developmental and reconstructive changes
      were not dependent on neuronal activity, the major exception being inhibitory
      synaptogenesis. The full complement of inhibitory synapses did not develop in the
      absence of neuronal activity, which could be mitigated by application of
      exogenous TrkB receptor ligands. Inhibitory synaptogenesis could also be promoted
      by activity-induced release of endogenous TrkB receptor ligands or by antibody
      activation of the TrkB receptor. 

PMID- 24933696
TI  - Discounting of monetary rewards that are both delayed and probabilistic: delay
      and probability combine multiplicatively, not additively.
AB  - The value of an outcome is affected both by the delay until its receipt (delay
      discounting) and by the likelihood of its receipt (probability discounting).
      Despite being well-described by the same hyperboloid function, delay and
      probability discounting involve fundamentally different processes, as revealed,
      for example, by the differential effects of reward amount. Previous research has
      focused on the discounting of delayed and probabilistic rewards separately, with
      little research examining more complex situations in which rewards are both
      delayed and probabilistic. In 2 experiments, participants made choices between
      smaller rewards that were both immediate and certain and larger rewards that were
      both delayed and probabilistic. Analyses revealed significant interactions
      between delay and probability factors inconsistent with an additive model. In
      contrast, a hyperboloid discounting model in which delay and probability were
      combined multiplicatively provided an excellent fit to the data. These results
      suggest that the hyperboloid is a good descriptor of decision making in
      complicated monetary choice situations like those people encounter in everyday
      life.

PMID- 24933697
TI  - Sleep can reduce the testing effect: it enhances recall of restudied items but
      can leave recall of retrieved items unaffected.
AB  - The testing effect refers to the finding that retrieval practice in comparison to
      restudy of previously encoded contents can improve memory performance and reduce
      time-dependent forgetting. Naturally, long retention intervals include both wake
      and sleep delay, which can influence memory contents differently. In fact, sleep
      immediately after encoding can induce a mnemonic benefit, stabilizing and
      strengthening the encoded contents. We investigated in a series of 5 experiments
      whether sleep influences the testing effect. After initial study of categorized
      item material (Experiments 1, 2, and 4A), paired associates (Experiment 3), or
      educational text material (Experiment 4B), subjects were asked to restudy encoded
      contents or engage in active retrieval practice. A final recall test was
      conducted after a 12-hr delay that included diurnal wakefulness or nocturnal
      sleep. The results consistently showed typical testing effects after the wake
      delay. However, these testing effects were reduced or even eliminated after
      sleep, because sleep benefited recall of restudied items but left recall of
      retrieved items unaffected. The findings are consistent with the bifurcation
      model of the testing effect (Kornell, Bjork, & Garcia, 2011), according to which
      the distribution of memory strengths across items is shifted differentially by
      retrieving and restudying, with retrieval strengthening items to a much higher
      degree than restudy does. On the basis of this model, most of the retrieved items
      already fall above recall threshold in the absence of sleep, so additional sleep
      induced strengthening may not improve recall of retrieved items any further.

PMID- 24933698
TI  - Piloting and path integration within and across boundaries.
AB  - Three experiments investigated whether navigation is less efficient across
      boundaries than within boundaries. In an immersive virtual environment,
      participants learned objects' locations in a large room or a small room.
      Participants then pointed to the objects' original locations after physically
      walking a circuitous path without vision. For participants who learned the
      objects in the large room, the testing position and the learning position were in
      the same room so that participants did not cross boundaries before testing; for
      participants who learned the objects in the small room, the testing position and
      the learning position were in 2 different rooms so that participants crossed
      boundaries before testing. Participants who learned the objects in the large
      room, during testing, either saw cues indicating the targets' locations (piloting
      group) or not (path integration group). Participants who learned the objects in
      the small room, during testing did not see any cues correctly indicating the
      targets' locations. The results showed that pointing accuracy was higher for
      those who learned the objects in the large room and in the piloting group than
      for those who learned the objects in the small room. However, this cross-boundary
      cost did not occur when we contrasted participants who learned objects in the
      large room and in the path integration group with participants who learned in a
      small room. These results suggested that navigation that relies on path
      integration only is not sensitive to boundary crossing, although navigation that
      relies on piloting is less efficient across boundaries than within boundaries.

PMID- 24933699
TI  - Using E-Z Reader to examine the consequences of fixation-location measurement
      error.
AB  - There is an ongoing debate about whether fixation durations during reading are
      only influenced by the processing difficulty of the words being fixated (i.e.,
      the serial-attention hypothesis) or whether they are also influenced by the
      processing difficulty of the previous and/or upcoming words (i.e., the attention
      gradient hypothesis). This article reports the results of 3 simulations that
      examine how systematic and random errors in the measurement of fixation locations
      can generate 2 phenomena that support the attention-gradient hypothesis:
      parafoveal-on-foveal effects and large spillover effects. These simulations
      demonstrate how measurement error can produce these effects within the context of
      a computational model of eye-movement control during reading (E-Z Reader;
      Reichle, 2011) that instantiates strictly serial allocation of attention, thus
      demonstrating that these effects do not necessarily provide strong evidence
      against the serial-attention hypothesis.

PMID- 24933700
TI  - Encoding and retrieval processes involved in the access of source information in
      the absence of item memory.
AB  - The current study sought to examine the relative contributions of encoding and
      retrieval processes in accessing contextual information in the absence of item
      memory using an extralist cuing procedure in which the retrieval cues used to
      query memory for contextual information were related to the target item but never
      actually studied. In Experiments 1 and 2, participants studied 1 category member
      (e.g., onion) from a variety of different categories and at test were presented
      with an unstudied category label (e.g., vegetable) to probe memory for item and
      source information. In Experiments 3 and 4, 1 member of unidirectional (e.g.,
      credit or card) or bidirectional (e.g., salt or pepper) associates was studied,
      whereas the other unstudied member served as a test probe. When recall failed,
      source information was accessible only when items were processed deeply during
      encoding (Experiments 1 and 2) and when there was strong forward associative
      strength between the retrieval cue and target (Experiments 3 and 4). These
      findings suggest that a retrieval probe diagnostic of semantically related item
      information reinstantiates information bound in memory during encoding that
      results in reactivation of associated contextual information, contingent upon
      sufficient learning of the item itself and the association between the item and
      its context information.

PMID- 24933701
TI  - Pushing typists back on the learning curve: contributions of multiple linguistic
      units in the acquisition of typing skill.
AB  - The present study investigated the way people acquire and control skilled
      performance in the context of typewriting. Typing skill was degraded by changing
      the location of a key (target key) while retaining the locations of other keys to
      disable an association between the letter and the key. We conducted 4
      experiments: Experiment 1 demonstrated that disabling a letter-key association
      affected not only the execution of the target keystroke but also the planning of
      other keystrokes for words involving the target key. In Experiments 2-4, typists
      practiced with a new target location and then transferred to a condition in which
      they typed the practiced words with the original key location (Experiment 2) or
      typed new words with the practiced key location (Experiments 3 and 4). Experiment
      2 showed that the newly acquired letter-key association interfered with the
      execution of the original keystroke but not planning. Experiments 3 and 4
      demonstrated that acquisition of the new letter-key association depended on
      multiple levels of linguistic units. Experiment 4 demonstrated that acquisition
      of the new association depended on sequences both before and after the target
      keystroke. We discuss implications of the results for 2 prominent approaches to
      modeling sequential behavior: hierarchical control and recurrent network models.

PMID- 24933702
TI  - When do words hurt? A multiprocess view of the effects of verbalization on visual
      memory.
AB  - Verbal overshadowing reflects the impairment in memory performance following
      verbalization of nonverbal stimuli. However, it is not clear whether the same
      mechanisms are responsible for verbal overshadowing effects observed with
      different stimuli and task demands. In the present article, we propose a
      multiprocess view that reconciles the main theoretical explanations of verbal
      overshadowing deriving from the use of different paradigms. Within a single
      paradigm, we manipulated both the nature of verbalization at encoding
      (nameability of the stimuli) and postencoding (verbal descriptions), as well as
      the nature (image transformation or recognition) and, by implication, the demands
      of the final memory task (global or featural). Results from 3 experiments
      replicated the negative effects of encoding and postencoding verbalization in
      imagery and recognition tasks, respectively. However, they also showed that the
      demands of the final memory task can modulate or even reverse verbal
      overshadowing effects due to both postencoding verbalization and naming during
      encoding.

PMID- 24933703
TI  - TMEPAI inhibits TGF-beta signaling by promoting lysosome degradation of TGF-beta
      receptor and contributes to lung cancer development.
AB  - Transforming growth factor-beta (TGF-beta) signaling plays important roles in
      embryogenesis and tumorigenesis by controlling cell growth, differentiation and
      migration. The transmembrane prostate androgen-induced protein (TMEPAI) is
      elevated in several cancers. TMEPAI expression is induced by TGF-beta signaling,
      and in turn, expression of TMEPAI negatively regulates TGF-beta signaling, but
      the molecular mechanisms of TMEPAI induced TGF-beta signaling inhibition are not
      well understood. Here we report that TMEPAI is localized to the lysosome and late
      endosome, and that association of TMEPAI with the E3 ubiquitin ligase Nedd4 is
      required for its transport to the lysosome. TMEPAI associates with the TGF-beta
      type I receptor (TbetaRI) and promotes its degradation in the lysosome. Depletion
      of TMEPAI in A549 lung cancer cells inhibits cell proliferation, migration and
      invasion, while TMEPAI expression in nude mice promotes tumorigenesis. These
      results reveal a novel function for TMEPAI in regulating TGF-beta signaling
      through the modulation of TbetaRI levels, which has important implications for
      cancer development in vivo.

PMID- 24933705
TI  - Theory of mind and switching predict prospective memory performance in
      adolescents.
AB  - Research indicates ongoing development of prospective memory as well as theory of
      mind and executive functions across late childhood and adolescence. However, so
      far the interplay of these processes has not been investigated. Therefore, the
      purpose of the current study was to investigate whether theory of mind and
      executive control processes (specifically updating, switching, and inhibition)
      predict prospective memory development across adolescence. In total, 42
      adolescents and 41 young adults participated in this study. Young adults
      outperformed adolescents on tasks of prospective memory, theory of mind, and
      executive functions. Switching and theory of mind predicted prospective memory
      performance in adolescents. 

PMID- 24933706
TI  - Event- and time-triggered remembering: the impact of attention deficit
      hyperactivity disorder on prospective memory performance in children.
AB  - The current study examined prospective memory (PM, both time-based and event
      based) and time estimation (TR, a time reproduction task) in children with and
      without attention deficit hyperactivity disorder (ADHD). This study also
      investigated the influence of task performance and TR on time-based PM in
      children with ADHD relative to controls. A sample of 69 children, aged 8 to 13
      years, completed the CyberCruiser-II time-based PM task, a TR task, and the Super
      Little Fisherman event-based PM task. PM performance was compared with children's
      TR abilities, parental reports of daily prospective memory disturbances
      (Prospective and Retrospective Memory Questionnaire for Children, PRMQC), and
      ADHD symptomatology (Conner's rating scales). Children with ADHD scored more
      poorly on event-based PM, time-based PM, and TR; interestingly, TR did not appear
      related to performance on time-based PM. In addition, it was found that PRMQC
      scores and ADHD symptom severity were related to performance on the time-based PM
      task but not to performance on the event-based PM task. These results provide
      some limited support for theories that propose a distinction between event-based
      PM and time-based PM.

PMID- 24933704
TI  - The epicardium signals the way towards heart regeneration.
AB  - From historical studies of developing chick hearts to recent advances in
      regenerative injury models, the epicardium has arisen as a key player in heart
      genesis and repair. The epicardium provides paracrine signals to nurture growth
      of the developing heart from mid-gestation, and epicardium-derived cells act as
      progenitors of numerous cardiac cell types. Interference with either process is
      terminal for heart development and embryogenesis. In adulthood, the dormant
      epicardium reinstates an embryonic gene programme in response to injury.
      Furthermore, injury-induced epicardial signalling is essential for heart
      regeneration in zebrafish. Given these critical roles in development, injury
      response and heart regeneration, the application of epicardial signals following
      adult heart injury could offer therapeutic strategies for the treatment of
      ischaemic heart disease and heart failure. 

PMID- 24933707
TI  - Multiple perpetrator rape among girls evaluated at a hospital-based child
      advocacy center: seven years of reviewed cases.
AB  - The aim of this study was to describe contextual events, abuse experiences, and
      disclosure processes of adolescents who presented to a hospital-based Child
      Advocacy Center for medical evaluation and evidentiary collection as indicated
      after experiencing multiple perpetrator rape during a single event (n=32) and to
      compare these findings to a group of single perpetrator sexual assaults (n=534).
      This study used a retrospective mixed-methods design with in-depth, forensic
      interviews and complete physical examinations of gang-raped adolescents. Patients
      ranged from 12 to 17 years (M=14 years). Girls who experienced multiple
      perpetrator rape during a single event were more likely to have run away, to have
      drunk alcohol in the past month, and to have participated in binge drinking in
      the past 2 weeks. Acute presentation of these victims were rare but 30% had
      hymenal transections and 38% had sexually transmitted infections (STIs). Forensic
      interviews revealed alcohol was a common weapon used by offenders, and its use
      resulted in victims experiencing difficulty in remembering and reporting details
      for police investigation or physical and mental health care. Most victims were
      raped at parties they attended with people they thought they could trust, and
      they felt let down by witnesses who could have helped but did not intervene.
      Although relatively rare, multiple perpetrator rape during a single event is a
      type of severe sexual assault experience and has significant risks for
      deleterious health outcomes. These victims require health care by trained
      providers to diagnose physical findings, treat STIs, screen for trauma, and
      support victims. 

PMID- 24933708
TI  - Child victims and poly-victims in China: are they more at-risk of family
      violence?
AB  - Multiple forms of violence may co-occur on a child. These may include various
      forms of child victimization and different types of family violence. However,
      evidence that child victims are more likely to witness other types of family
      violence has been lacking in China. Using data of a large and diverse sample of
      children recruited from 6 regions in China during 2009 and 2010 (N=18,341; 47%
      girls; mean age=15.9 years), the associations between child victimization and
      family violence witnessed were examined. Descriptive statistics and the
      associations between child victimization, demographic characteristics, and family
      violence witnessed were analyzed. Lifetime and preceding-year rates were 71.7%
      and 60.0% for any form of child victimization and 14.0% and 9.2% for poly
      victimization (having four or more types of victimization), respectively. Family
      disadvantages (i.e., lower socio-economic status, single parents, and having more
      than one child in the family) were associated with child victimization and poly
      victimization. Witnessing of parental intimate partner violence, elder abuse, and
      in-law conflict also increased the likelihood of child victimization and poly
      victimization, even after the adjustment of demographic factors. Possible
      mechanisms for the links between family violence and child victimization are
      discussed. The current findings indicated the need for focusing on the whole
      family rather than the victim only. For example, screening for different types of
      family violence when child victims are identified may help early detection of
      other victims within the family. 

PMID- 24933709
TI  - Acquired cholesteatoma in children: clinical features and surgical outcome.
AB  - OBJECTIVE: In general, cholesteatoma tends to recur more frequently in children
      than in adults. This has been suggested to be due to immature Eustachian tube
      function, underdeveloped mastoid air cells, and subsequent repetitive otitis
      media in children. This study was undertaken to determine the characteristics of
      acquired cholesteatoma in children by comparison with that in adults. METHODS: We
      retrospectively evaluated 42 children with acquired cholesteatoma (males, 38;
      females, 4; age range, 3-15 years) using medical records from January 1999 to
      December 2009 at the Department of Otolaryngology, Niigata University Hospital.
      The extent of disease was classified according to the Classification and Staging
      of cholesteatoma proposed by the Japan Otological Society in 2010. RESULTS: No
      major differences in stage classification were observed between children and
      adults. In children with pars flaccida-type cholesteatoma, the epithelium tended
      to invade from the attic to the mastoid cavity and mesotympanum. In contrast,
      adult patients with invasion to the mesotympanum were fewer. The rate of
      disappearance of the stapes superstructure was almost the same in children and in
      adults. The destruction of the superstructure of the stapes was more common in
      pars tensa type than pars flaccida type; so it was dependent on the pathology.
      Postoperative hearing levels were better in children, even in those with
      widespread lesions. However, the recurrence rate was significantly higher in
      children. CONCLUSIONS: Acquired cholesteatoma in children showed a wider
      invasion, and the recurrence rates were higher than that in adults. For patients
      with a widespread lesion and severe destruction of the ossicles, a two-stage
      surgery is recommended.

PMID- 24933711
TI  - Upper aero-digestive contamination by Pseudomonas aeruginosa and implications in
      Cystic Fibrosis.
AB  - BACKGROUND: Cystic Fibrosis (CF) is a severe genetic disorder that is common
      among the Caucasian population. Bacterial respiratory infections are the main
      cause of morbidity and mortality in CF patients. Pseudomonas aeruginosa is the
      main pathogen of lower airways (LAW) decline. METHOD: To understand chronic
      broncho-pulmonary colonization, a systematic review is conducted. The aim of our
      article is to identify the pathways of contamination in the upper aero-digestive
      tract. RESULTS: A large number of articles report that P. aeruginosa is
      established first at nasopharyngeal sites. The vast majority of authors agree
      that the upper aero-digestive tract is the first location of colonization by P.
      aeruginosa and its presence appears to be predictive of subsequent broncho
      pulmonary colonization. CONCLUSION: This review supports the possible involvement
      of the nasal and paranasal sinuses and oral cavity as means of contamination.

PMID- 24933710
TI  - Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction.
AB  - OBJECTIVE: Mutations of transmembrane channel-like 1 gene (TMC1) can cause
      dominant (DFNA36) or recessive (DFNB7/B11) deafness. In this article, we describe
      the characteristics of DFNA36 and DFNB7/B11 deafness, the features of the Tmc1
      mutant mouse strains, and recent advances in our understanding of TMC1 function.
      METHODS: Publications related to TMC1, DFNA36, or DFNB7/B11 were identified
      through PubMed. RESULTS: All affected DFNA36 subjects showed post-lingual,
      progressive, sensorineural hearing loss (HL), initially affecting high
      frequencies. In contrast, almost all affected DFNB7/B11 subjects demonstrated
      congenital or prelingual severe to profound sensorineural HL. The mouse Tmc1 gene
      also has dominant and recessive mutant alleles that cause HL in mutant strains,
      including Beethoven, deafness, and Tmc1 knockout mice. These mutant mice have
      been instrumental for revealing that Tmc1 and its closely related paralog Tmc2
      are expressed in cochlear and vestibular hair cells, and are required for hair
      cell mechanoelectrical transduction (MET). Recent studies suggest that TMC1 and
      TMC2 may be components of the long-sought hair cell MET channel. CONCLUSION: TMC1
      mutations disrupt hair cell MET.

PMID- 24933712
TI  - Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal
      neovascularization model.
AB  - Inflammatory angiogenesis is the pathogenic mechanism of various sight
      threatening eye diseases, among them corneal neovascularization. Current
      treatment options include steroids which have undesirable side effects, or anti
      VEGF which has only limited efficacy. In an inflammatory environment, however,
      angiogenesis can be stimulated by numerous factors not directly targeted by anti
      VEGF therapy. The aim of this study was to induce corneal inflammation leading to
      angiogenesis, and investigate the early, differential effects of steroid and anti
      VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two
      Wistar rats received a single intrastromal corneal suture to induce a controlled
      inflammatory angiogenic response. Rats were subsequently treated with
      dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times
      daily for 7 days. In vivo confocal microscopy of the cornea was performed
      longitudinally from 5 h up to 7 d to investigate morphology at the cellular and
      tissue-level. In vivo photographic vessel analysis and immunohistochemistry were
      also performed. RT-PCR for VEGF-A, FGF-2, IL-6, TNF-alpha, CXCL2, CCL2, CCL3 and
      DLL4 was performed at 24 h, and for VEGF-A, IL-6, TNF-alpha, FGF-2, CXCL2, CCL2,
      and CCL3 at 7 days. Early infiltration of CD11b + myeloid cells into the cornea
      at 5 h post-suture was delayed by both treatments relative to controls; however
      neither treatment was able to suppress accumulation of myeloid cells at day 2 or
      7. Limbal vessel dilation was inhibited at 5 h by both treatments, but only
      dexamethasone showed sustained effect until day 2. Early macrophage recruitment
      was also suppressed by dexamethasone (but not by anti-VEGF) until day 2.
      Dexamethasone furthermore suppressed corneal neovascularization at day 7 by over
      90%, whereas suppression by anti-VEGF was 14%. Despite differential suppression
      of vessel dilation, macrophage recruitment, and vascular invasion, anti-VEGF and
      dexamethasone both down-regulated VEGF-A and IL-6 expression at 24 h with
      sustained effect to 7 d. They also both down regulated FGF-2 and TNF-alpha at 24
      h and CCL2 at 7 d. In conclusion, anti-angiogenic treatments influence early, pre
      angiogenic tissue activity such as limbal vessel dilation, inflammatory cell
      infiltration of the stroma, and macrophage recruitment. Importantly, the
      differential effects of steroids and anti-VEGF treatment in suppressing
      neovascular growth could not be attributed to differential inhibition of several
      major angiogenic and inflammatory factors in the early pre-sprouting phase,
      including IL-6, VEGF-A, FGF-2, TNF-alpha, CCL2, CCL3, CXCL2, or DLL4. 

PMID- 24933713
TI  - Submodalities of emotion in the context of cingulate subregions.

PMID- 24933714
TI  - Tumor progression during preoperative chemotherapy predicts failure to complete 2
      stage hepatectomy for colorectal liver metastases: results of an Italian
      multicenter analysis of 130 patients.
AB  - BACKGROUND: We aimed to evaluate the feasibility and long-term results of 2-stage
      hepatectomy (TSH) in patients with bilobar colorectal liver metastases (CRLM).
      STUDY DESIGN: We performed a retrospective multicenter study including 4 Italian
      hepatobiliary surgery units. One hundred thirty patients were selected for TSH
      between 2002 and 2011. The primary endpoint was feasibility of TSH and analysis
      of factors associated with failure to complete the procedure. The secondary
      endpoint was the long-term survival analysis. RESULTS: Patients presented with
      synchronous CRLM in 80.8% of cases, with a mean number of 8.3 CRLM and with
      concomitant extrahepatic disease in 20.0% of cases. The rate of failure to
      complete TSH was 21.5% and tumor progression was the most frequent reason for
      failure (18.5% of cases). Primary tumor characteristics, type, number, and
      distribution of CRLM were not associated with significantly different risks of
      disease progression. Multivariable logistic regression analysis showed that tumor
      progression during prehepatectomy chemotherapy was the only independent risk
      factor for failure to complete TSH. The 5- and 10-year overall survival rates for
      patients who completed TSH were 32.1% and 24.1%, respectively, with a median
      survival of 43 months. Duration of prehepatectomy chemotherapy >=6 cycles was
      found to be the only independent predictor of overall and disease-free survival.
      CONCLUSIONS: This study showed that selection of patients by response to
      prehepatectomy chemotherapy may be extremely important before planning TSH
      because tumor progression while receiving prehepatectomy chemotherapy was
      associated with significantly higher risk of failure to complete the second
      stage. For patients who completed the TSH strategy, long-term outcomes can be
      achieved with results similar to those observed after single-stage hepatectomy.

PMID- 24933716
TI  - [Cardiovascular morbimortality after a follow-up of six years in black
      hypertensive in South Algeria].
AB  - INTRODUCTION: Arterial hypertension is a major public health problem not only
      internationally, but also in our country, and it is the major risk factor for
      cardiovascular diseases. In south Algeria, the black population is nearly half
      the population of the oases of the Algerian Sahara. THE OBJECTIVES OF THE STUDY:
      The objectives of the study are to analyze the long-term fate of the black
      hypertensive subjects in Algerian oases in southern Algeria, in terms of
      morbidity and mortality, comparing the morphometric profile and cardiovascular
      complications with the white population of the same oases. MATERIALS AND METHODS:
      One thousand four hundred and twenty-five subjects of both sexes were included
      (811 blacks and 614 white subjects), aged 40 and older, living in the Algerian
      Sahara and were reviewed after six years of decline. The control consisted of
      filling a questionnaire oriented on civil status, target organ damage, the number
      of hospitalizations and mortality. All calculations and statistical analyzes are
      processed by the SPSS 17.0 and Epi Info6 software. RESULTS: Mean age for the
      black population and the white population was 60.3+/-11.1 and 58.6+/-10.6years,
      respectively. The incidence of hypertension was 50 % among blacks. The main
      complications observed were: stroke in 3.8 %, heart failure in 3.1 %, myocardial
      infarction in 1.7 %, hospitalizations related to cardiovascular complications of
      the black population was around 4.4 %, mortality 5.4 %. CONCLUSION: These data on
      hypertension black subjects emphasize the importance of a policy of adequate
      local health issues raised, both in terms of the management of hypertension, as
      in investment in local medical research.

PMID- 24933715
TI  - Comparison of comorbidity collection methods.
AB  - BACKGROUND: Multiple valid comorbidity indices exist to quantify the presence and
      role of comorbidities in cancer patient survival. Our goal was to compare chart
      based Adult Comorbidity Evaluation-27 index (ACE-27) and claims-based Charlson
      Comorbidity Index (CCI) methods of identifying comorbid ailments and their
      prognostic abilities. STUDY DESIGN: We conducted a prospective cohort study of
      6,138 newly diagnosed cancer patients at 12 different institutions. Participating
      registrars were trained to collect comorbidities from the abstracted chart using
      the ACE-27 method. The ACE-27 assessment was compared with comorbidities captured
      through hospital discharge face sheets using ICD coding. The prognostic
      accomplishments of each comorbidity method were examined using follow-up data
      assessed at 24 months after data abstraction. RESULTS: Distribution of the ACE-27
      scores was: "none" for 1,453 (24%) of the patients; "mild" for 2,388 (39%);
      "moderate" for 1,344 (22%), and "severe" for 950 (15%) of the patients. Deyo's
      adaption of the CCI identified 4,265 (69%) patients with a CCI score of 0, and
      the remaining 31% had CCI scores of 1 (n = 1,341 [22%]), 2 (n = 365 [6%]), or 3
      or more (n = 167 [3%]). Of the 4,265 patients with a CCI score of zero, 394 (9%)
      were coded with severe comorbidities based on ACE-27 method. A higher comorbidity
      score was significantly associated with higher risk of death for both comorbidity
      indices. The multivariable Cox model, including both comorbidity indices, had the
      best performance (Nagelkerke's R(2) = 0.37) and the best discrimination (C index
      = 0.827). CONCLUSIONS: The number, type, and overall severity of comorbid
      ailments identified by chart- and claims-based approaches in newly diagnosed
      cancer patients were notably different. Both indices were prognostically
      significant and able to provide unique prognostic information.

PMID- 24933717
TI  - Effect of oculomotor rehabilitation on accommodative responsivity in mild
      traumatic brain injury.
AB  - Accommodative dysfunction is a common oculomotor sequelae of mild traumatic brain
      injury (mTBI). This study evaluated a range of dynamic (objective) and static
      (subjective) measures of accommodation in 12 nonstrabismic individuals with mTBI
      and near vision-related symptoms before and after oculomotor training (OMT) and
      placebo (P) training (6 wk, two sessions per week, 3 h of training each).
      Following OMT, the dynamics of accommodation improved markedly. Clinically, there
      was a significant increase in the maximum accommodative amplitude both
      monocularly and binocularly. In addition, the near vision symptoms reduced along
      with improved visual attention. None of the measures were found to change
      significantly following P training. These results provide evidence for a
      significant positive effect of the accommodatively based OMT on accommodative
      responsivity. Such improvement is suggestive of oculomotor learning,
      demonstrating considerable residual brain-visual system plasticity in the adult
      compromised brain. 

PMID- 24933718
TI  - Influence of physical capacities of males with transtibial amputation on gait
      adjustments on sloped surfaces.
AB  - The aim of the study was to investigate how kinematic and kinetic adjustments
      between level and slope locomotion of persons with transtibial amputation are
      related to their individual muscular and functional capacities. A quantified gait
      analysis was conducted on flat and slope surfaces for seven patients with
      transtibial amputation and a control group of eight subjects to obtain
      biomechanical parameters. In addition, maximal isometric muscular strength (knee
      and hip extensors) and functional scores were measured. The results of this study
      showed that most of the persons with transtibial amputation could adapt to ramp
      ascent either by increasing ankle, knee, and hip flexion angles of the residual
      limb and/or by recruiting their hip extensors to guarantee enough hip extension
      power during early stance. Besides, 6-minute walk test score was shown to be a
      good predictor of adaptation capacities to slope ascent. In ramp descent, the
      increase of knee flexion moment was correlated with knee extensor strength and
      residual-limb length. However, no correlation was observed with functional
      parameters. Results show that the walking strategy adopted by persons with
      transtibial amputation to negotiate ramp locomotion mainly depends on their
      muscular capacities. Therefore, muscular strengthening should be a priority
      during rehabilitation. 

PMID- 24933719
TI  - How do walking, standing, and resting influence transtibial amputee residual limb
      fluid volume?
AB  - The purpose of this research was to determine how fluid volume changes in the
      residual limbs of people with transtibial amputation were affected by activity
      during test sessions with equal durations of resting, standing, and walking.
      Residual limb extracellular fluid volume was measured using biompedance analysis
      in 24 participants. Results showed that all subjects lost fluid volume during
      standing with equal weight-bearing, averaging a loss rate of -0.4%/min and a mean
      loss over the 25 min test session of 2.6% (standard deviation [SD] 1.1). Sixteen
      subjects gained limb fluid volume during walking (mean gain of 1.0% [SD 2.5]),
      and fifteen gained fluid volume during rest (mean gain of 1.0% [SD 2.2]). Walking
      explained only 39.3% of the total session fluid volume change. There was a strong
      correlation between walk and rest fluid volume changes (-0.81). Subjects with
      peripheral arterial disease experienced relatively high fluid volume gains during
      sitting but minimal changes or losses during sit-to-stand and stand-to-sit
      transitioning. Healthy female subjects experienced high fluid volume changes
      during transitioning from sit-to-stand and stand-to-sit. The differences in fluid
      volume response among subjects suggest that volume accommodation technologies
      should be matched to the activity-dependent fluid transport characteristics of
      the individual prosthesis user. 

PMID- 24933721
TI  - Sensor-based hip control with hybrid neuroprosthesis for walking in paraplegia.
AB  - The objectives of this study were to test whether a hybrid neuroprosthesis (HNP)
      with an exoskeletal variable-constraint hip mechanism (VCHM) combined with a
      functional neuromuscular stimulation (FNS) controller can maintain upright
      posture with less upper-limb support and improve gait speed as compared with
      walking with either an isocentric reciprocating gait orthosis (IRGO) or FNS only.
      The results show that walking with the HNP significantly reduced forward lean in
      FNS-only walking and the maximum upper-limb forces by 42% and 19% as compared
      with the IRGO and FNS-only gait, respectively. Walking speed increased
      significantly with VCHM as compared with 1:1 reciprocal coupling and by 15% when
      using the sensor-based FNS controller as compared with HNP with fixed baseline
      stimulation without the controller active. 

PMID- 24933720
TI  - Increased reward in ankle robotics training enhances motor control and cortical
      efficiency in stroke.
AB  - Robotics is rapidly emerging as a viable approach to enhance motor recovery after
      disabling stroke. Current principles of cognitive motor learning recognize a
      positive relationship between reward and motor learning. Yet no prior studies
      have established explicitly whether reward improves the rate or efficacy of
      robotics-assisted rehabilitation or produces neurophysiologic adaptations
      associated with motor learning. We conducted a 3 wk, 9-session clinical pilot
      with 10 people with chronic hemiparetic stroke, randomly assigned to train with
      an impedance-controlled ankle robot (anklebot) under either high reward (HR) or
      low reward conditions. The 1 h training sessions entailed playing a seated video
      game by moving the paretic ankle to hit moving onscreen targets with the anklebot
      only providing assistance as needed. Assessments included paretic ankle motor
      control, learning curves, electroencephalograpy (EEG) coherence and spectral
      power during unassisted trials, and gait function. While both groups exhibited
      changes in EEG, the HR group had faster learning curves (p = 0.05), smoother
      movements (p </= 0.05), reduced contralesional-frontoparietal coherence (p </=
      0.05), and reduced left-temporal spectral power (p </= 0.05). Gait analyses
      revealed an increase in nonparetic step length (p = 0.05) in the HR group only.
      These results suggest that combining explicit rewards with novel anklebot
      training may accelerate motor learning for restoring mobility. 

PMID- 24933722
TI  - Complex muscle vibration patterns to induce gait-like lower-limb movements: proof
      of concept.
AB  - Muscle vibrations can induce motor responses and illusions of complex movements.
      However, inducing gait-like cyclical movements and illusions requires the
      application of multiple fast alternating vibrations to lower-limb muscles. The
      objectives were (1) to test the feasibility of delivering complex vibrations in a
      time-organized manner and (2) to illustrate the possibility of inducing alternate
      gait-in-place-like movements using these vibrations. Patterns of vibration,
      produced by 12 vibrators applied bilaterally on the flexor and extensor muscle
      groups of the lower limbs, were based on normal gait kinematics. We tested 1 s
      and 2 s cycle patterns of vibration. Vibrator responses were assessed using auto-
      and crosscorrelations and frequency analyses based on accelerometry measurements,
      and compared between patterns. High auto- (>0.8) and crosscorrelation (>0.6)
      coefficients demonstrated a good response by the vibrators to the control signal.
      Vibrations induced cyclical, low-amplitude stepping-in-place movements that
      mimicked alternate walking movements with both legs, with 1 s and 2 s cycle
      durations, in one nondisabled participant and one participant with American
      Spinal Injury Association Impairment Scale B spinal cord injury standing,
      relaxed, with body-weight support. Electromechanical vibrators can deliver
      complex cyclical vibrations and trigger gait-like lower-limb movements. These
      results warrant the application of these vibration patterns on individuals with
      sensorimotor impairments to test their potential in gait rehabilitation. 

PMID- 24933723
TI  - Comparison of body-powered voluntary opening and voluntary closing prehensor for
      activities of daily life.
AB  - Persons with an upper-limb amputation who use a body-powered prosthesis typically
      control the prehensor through contralateral shoulder movement, which is
      transmitted through a Bowden cable. Increased cable tension either opens or
      closes the prehensor; when tension is released, some passive element, such as a
      spring, returns the prehensor to the default state (closed or open). In this
      study, we used the Southampton Hand Assessment Procedure to examine functional
      differences between these two types of prehensors in 29 nondisabled subjects (who
      used a body-powered bypass prosthesis) and 2 persons with unilateral transradial
      amputations (who used a conventional body-powered device). We also administered a
      survey to determine whether subjects preferred one prehensor or the other for
      specific tasks, with a long-term goal of assessing whether a prehensor that could
      switch between both modes would be advantageous. We found that using the
      voluntary closing prehensor was 1.3 s faster (p = 0.02) than using the voluntary
      opening prehensor, across tasks, and that there was consensus among subjects on
      which types of tasks they preferred to do with each prehensor type. Twenty-five
      subjects wanted a device that could switch between the two modes in order to
      perform particular tasks. 

PMID- 24933724
TI  - Performance-based assessment of falls risk in older veterans with executive
      dysfunction.
AB  - Falling is a serious hazard for older veterans that may lead to severe injury,
      loss of independence, and death. While the American Geriatrics Society (AGS)
      provides guidelines to screen individuals at risk for falls, the guidelines may
      be less successful with specific subgroups of patients. In a veteran sample, we
      examined whether the Timed Up and Go (TUG) test, including a modified version,
      the TUG-Cognition, effectively detected potential fallers whose risk was
      associated with cognitive deficits. Specifically, we sought to determine whether
      TUG tasks and AGS criteria were differentially associated with executive
      dysfunction, whether the TUG tasks identified potential fallers outside of those
      recognized by AGS criteria, and whether these tasks distinguished groups of
      fallers. Participants included 120 mostly male patients referred to the Memory
      Assessment Clinic because of cognitive impairment. TUG-Cognition scores were
      strongly associated with executive dysfunction and differed systematically
      between fallers grouped by number of falls. These findings suggest that the TUG
      Cognition shows promise in identifying fallers whose risk is related to or
      compounded by cognitive impairment. Future research should study the predictive
      validity of these measures by following patients prospectively. 

PMID- 24933725
TI  - Evaluation of two cane instruments in older adults with knee osteoarthritis.
AB  - The objectives of this study were to describe the psychometric properties of the
      Cane Cognitive Mediator Scale (CCMS) and the Psychosocial Impact of Assistive
      Devices Scale (PIADS) in adults with knee osteoarthritis (OA) and to determine
      the feasibility of applying these instruments as screening tools to identify
      patients with the propensity to use a cane. Data from a randomized crossover
      trial were analyzed for 53 older adults with knee OA. Perceptions on using a cane
      were measured at baseline using the CCMS and PIADS. The CCMS was repeated 1 wk
      later. At 6 mo, subjects rated their intention to use a cane. The findings
      indicated that 1 wk test-retest reliability was acceptable for the CCMS Attitudes
      and Subjective Norms subscales (r = 0.48 to 0.93) and low for the CCMS Perceived
      Behavioral Control subscale (r = 0.15). Internal consistency reliability was good
      for each CCMS and PIADS subscale. The CCMS Subjective Norms subscale demonstrated
      acceptable predictive validity across all subgroups (r = 0.53 to 0.88). The PIADS
      Adaptability subscale demonstrated acceptable predictive validity for the 45 to
      64 yr-old age group (r = 0.54). The findings indicate that the CCMS Subjective
      Norms subscale exhibits good psychometric properties and has potential
      application as a screening tool. 

PMID- 24933726
TI  - PTSD is negatively associated with physical performance and physical function in
      older overweight military Veterans.
AB  - This study examines the effect of posttraumatic stress disorder (PTSD) on
      function and physical performance in older overweight military Veterans with
      comorbid conditions. This is a secondary data analysis of older Veterans (mean
      age = 62.9 yr) participating in a physical activity counseling trial. Study
      participants with PTSD (n = 67) and without PTSD (n = 235) were identified. Self
      reported physical function (36-item Short Form Health Survey) and directly
      measured physical performance (mobility, aerobic endurance, strength) were
      assessed. Multivariate analyses of variance controlling for demographic factors
      and psychiatric disorders demonstrated significant physical impairment among
      those with PTSD. PTSD was negatively associated with self-reported physical
      function, functioning in daily activities, and general health (p < 0.01). Those
      with PTSD also performed significantly worse on tests of lower-limb function (p <
      0.05). Despite being significantly younger, Veterans with PTSD had comparable
      scores on gait speed, aerobic endurance, grip strength, and bodily pain compared
      with Veterans without PTSD. This study provides preliminary data for the negative
      association between PTSD and physical function in older military Veterans. These
      data highlight the importance of ongoing monitoring of physical performance among
      returning Veterans with PTSD and intervening in older overweight Veterans with
      PTSD, whose physical performance scores are indicative of accelerated risk of
      premature functional aging. 

PMID- 24933727
TI  - Elastic head support for persons with amyotrophic lateral sclerosis.
AB  - This article describes an inexpensive elastic head support for persons with
      amyotrophic lateral sclerosis (ALS) and neck muscle weakness and also presents a
      case series to examine its effectiveness. The device offers support to the head
      while the user is seated, standing, and walking, providing support for persons in
      various stages of ALS. The head support system was tested in seven male patients
      with ALS. Before and after the 2 wk trial, the subjects answered questions
      related to their communication efficacy, difficulty swallowing, level of neck
      discomfort, number of hours being upright before neck discomfort, comfort in
      social settings, and rating of perceived dyspnea. Subjects also answered specific
      questions related to the elastic head support after the 2 wk trial. The results
      suggested that the elastic head support is useful for some, but not all,
      patients. 

PMID- 24933729
TI  - New methods for evaluating physical and thermal comfort properties of orthotic
      materials used in insoles for patients with diabetes.
AB  - Orthotic insoles are commonly used in the treatment of the diabetic foot to
      prevent ulcerations. Choosing suitable insole material is vital for effective
      foot orthotic treatment. We examined seven types of orthotic materials. In
      consideration of the key requirements and end uses of orthotic insoles for the
      diabetic foot, including accommodation, cushioning, and control, we developed
      test methods for examining important physical properties, such as force reduction
      and compression properties, insole-skin friction, and shear properties, as well
      as thermal comfort properties of fabrication materials. A novel performance index
      that combines various material test results together was also proposed to
      quantify the overall performance of the insole materials. The investigation
      confirms that the insole-sock interface has a lower coefficient of friction and
      shearing stress than those of the insole-skin interface. It is also revealed that
      material brand and the corresponding density and cell volume, as well as
      thickness, are closely associated with the performance of moisture absorption and
      thermal comfort. On the basis of the proposed performance index, practitioners
      can better understand the properties and performance of various insole materials,
      thus prescribing suitable orthotic insoles for patients with diabetic foot. 

PMID- 24933728
TI  - Detraining outcomes with expiratory muscle strength training in Parkinson
      disease.
AB  - Expiratory muscle strength training (EMST) is efficacious for improving maximum
      expiratory pressure (MEP), cough function, and swallowing safety in Parkinson
      disease (PD). However, there are no published reports describing detraining
      effects following EMST in persons with PD. Moreover, there are no published
      reports describing detraining effects following any behavioral swallowing
      intervention. Ten participants with PD underwent 3 mo of detraining following
      EMST. Measures of MEP and swallowing safety were made prior to beginning EMST
      (baseline), posttreatment (predetraining), and 3 mo postdetraining. Participants
      demonstrated, on average, a 19% improvement in MEP from pre- to post-EMST.
      Following the 3 mo detraining period, MEP declined by 2% yet remained 17% above
      the baseline value. No statistically significant changes were found in swallowing
      safety from post-EMST to postdetraining period. Following the 3 mo detraining
      period, seven participants demonstrated no change in swallowing safety, one
      worsened, and two had improvements. This preliminary study highlights the need
      for the design of maintenance programs to sustain function following intensive
      periods of training. 

PMID- 24933730
TI  - Sound transmission by cartilage conduction in ear with fibrotic aural atresia.
AB  - A hearing aid using cartilage conduction (CC) has been proposed as an alternative
      to bone conduction (BC) hearing aids. The transducer developed for this
      application is lightweight, requires a much smaller fixation force than a BC
      hearing aid, and is more convenient to use. CC can be of great benefit to
      patients with fibrotic aural atresia. Fibrotic tissue connected to the ossicles
      provides an additional pathway (termed fibrotic tissue pathway) for sound to
      reach the cochlea by means of CC. To address the function of fibrotic tissue
      pathway, BC and CC thresholds were measured in six ears with fibrotic aural
      atresia. The relationship between the CC thresholds and the results of computed
      tomography was investigated. In the ears with the presence of a fibrotic tissue
      pathway, the CC thresholds were lower than the BC thresholds at 0.5 and 1.0 kHz.
      At 2.0 kHz, no significant difference was observed between the BC and CC
      thresholds. The current findings suggest that sound in the low to middle
      frequency range is transmitted more efficiently by CC via a fibrotic tissue
      pathway than BC. The development of hearing devices using CC can contribute to
      rehabilitation, particularly in patients with fibrotic aural atresia. 

PMID- 24933731
TI  - Phosphorylation of Akt at the C-terminal tail triggers Akt activation.
AB  - Aberrant hyper-activation of the protein kinase Akt plays a critical role in
      promoting tumorigenesis. Mechanistically, previous studies establish that
      phosphorylation of Akt at S473 and T308 by mTORC2 and PDK1, respectively, is
      necessary for its full activation, thereby having been used as Akt activation
      markers. Recently, we report that phosphorylation of S477 and T479 at the extreme
      C-terminus of Akt1 promotes Akt1 activation. We further demonstrate that Akt1
      pS477 and pT479 events are governed by Cdk2/Cyclin A or mTORC2 under distinct
      cellular contexts such as cell cycle progression or growth stimulation
      conditions. Here, we summarize our major findings regarding the biological
      significance for pS477/pT479-mediated activation of Akt and also provide
      perspectives for future follow-up studies. 

PMID- 24933732
TI  - Donor parity no longer a barrier for female-to-male hematopoietic stem cell
      transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied
      treatment for disorders mainly involving the hematopoietic system. The success of
      this treatment depends on many different patient- and donor-specific factors.
      Based on higher CD34+ yields and superior clinical outcomes associated with the
      use of male donors, males are generally seen as the preferred HSCT donor. In
      addition, female donors are notorious for bearing memory type lymphocytes induced
      by previous pregnancies; such alloimmune cells may provoke unwanted immune
      reactions such as graft-vs.-host disease in transplant recipients. Consequently,
      many transplant centers try to avoid parous donors, particularly when searching
      the best unrelated donor for a male patient. We recently showed that parous women
      with female offspring have an anti-male directed tolerogenic immune status
      comparable to that of nulliparous donors. As discussed in this article addendum,
      the sex of the donor's offspring combined with the presence of HY-specific T
      regulator cells are possibly better selection criteria than parity status per se.

PMID- 24933734
TI  - Editorial: culture and psychiatry.

PMID- 24933733
TI  - Is there unity in an image?

PMID- 24933735
TI  - [Quantitative assessment on physical activity among Chinese adults aged 18 to 60
      years old in three provinces].

PMID- 24933736
TI  - [Epidemiological analysis on the deaths of hand-foot-mouth disease in Guizhou
      province, 2012].

PMID- 24933737
TI  - Primary delusional parasitosis treated effectively with paliperidone.

PMID- 24933739
TI  - Colonoscopic localisation of colorectal  tumours.

PMID- 24933738
TI  - Schizophrenia: cracked but on the way to repair.

PMID- 24933740
TI  - Gene expression analysis for prostate cancer management.

PMID- 24933741
TI  - Myocardial sympathetic innervation imaging in heart failure.

PMID- 24933742
TI  - Artificial intervertebral disc arthroplasty for treatment of degenerative disc
      disease of the cervical spine.

PMID- 24933743
TI  - Artificial pancreas device systems.

PMID- 24933744
TI  - Special report: screening asymptomatic women with dense breasts and normal
      mammograms for breast cancer.

PMID- 24933745
TI  - Parotid gland pleomorphic adenoma with floret-like tyrosine-rich crystals.

PMID- 24933746
TI  - An aripiprazole discontinuation syndrome.
AB  - Major depression is a common and debilitating illness. Over recent years, new
      pharmacologic treatments have been approved for this disorder, including the
      atypical antipsychotics. One of the benefits of these medications is their
      significant efficacy as augmenting agents for unipolar, nonpsychotic major
      depressive disorder (MDD).Aripiprazole (marketed as Abilify, Bristol-Myers
      Squibb/ Otsuka Pharmaceuticals) was the first medication of this class approved
      for adjunctive treatment of MDD, and is the 5th most commonly prescribed
      medication in the United States in 2010. However, despite the frequency of its
      use, little has been described regarding events surrounding aripiprazole
      discontinuation. Here I describe what is, to my knowledge, the first reported
      case of an aripiprazole discontinuation syndrome. While directly relevant to
      psychiatrists and behavioral specialists, the symptoms described here are
      pertinent for internists and neurologists who may encounter this medication in
      their clinical practice.

PMID- 24933747
TI  - Phlegmonous colitis associated with advanced liver disease: case report and novel
      radiological signs.

PMID- 24933748
TI  - Q & A with Dr. Gowri Anandarajah on spirituality and medicine.

PMID- 24933749
TI  - Broad hardship exemptions could make mandate a paper tiger.

PMID- 24933750
TI  - Enrollment groups learning from mistakes in marketing to Latinos.

PMID- 24933751
TI  - State boards' policy for telemedicine may present roadblocks.

PMID- 24933752
TI  - Rethinking spine care.

PMID- 24933753
TI  - An early system integration visionary.

PMID- 24933754
TI  - Dedicated to molding new leaders.

PMID- 24933755
TI  - Leadership through relationships.

PMID- 24933756
TI  - Shelter for convalescence.

PMID- 24933757
TI  - Where should you go for cancer care?

PMID- 24933758
TI  - Medical home findings out-of-date.

PMID- 24933760
TI  - Redefining healthcare leadership.

PMID- 24933759
TI  - Don't downplay patient satisfaction.

PMID- 24933761
TI  - A hippocratic oath for healthcare managers.

PMID- 24933762
TI  - Employers must keep pressuring providers on costs.

PMID- 24933763
TI  - When things are not to your liking.

PMID- 24933764
TI  - The state of professional discipline in 2013.

PMID- 24933765
TI  - Time well spent.

PMID- 24933766
TI  - When the dentist and patient don't agree.

PMID- 24933767
TI  - Septic arthritis of the shoulder in a dental patient: a case report and review.
AB  - Septic arthritis of the glenohumoral joint is rare following dental procedures,
      comprising approximately 3% of all joint infections. Septic arthritis following
      bacteremia from dental procedures is uncommon and generally occurs in prosthetic
      joints. Predisposing causes may include immunocompromising diseases such as
      diabetes, HIV infection, renal failure and intravenous drug abuse. We report a
      rare case of unilateral glenohumoral joint septic arthritis in a 60-year-old male
      patient (without a prosthetic joint) secondary to a dental procedure. The
      insidious nature of the presentation is highlighted. Septic arthritis infections,
      though rare, require a high level of clinical suspicion. Vague symptoms of
      shoulder pain may mask the initial diagnosis, as was the case in our patient.
      Incision and drainage via surgical intervention are often required, followed by
      parenteral antibiotics.

PMID- 24933769
TI  - Dental management of florid cemento-osseous dysplosia.
AB  - Cemento-osseous dysplasia encompasses several different clinical and radiographic
      presentations, including periapical, focal and florid cemento-osseous dysplasia
      (FCOD). FCOD is usually asymptomatic and discovered only fortuitously. No
      treatment is required unless the lesion is secondarily infected. Oral hygiene
      advice should be emphasized for patients with FCOD to prevent caries and
      periodontal diseases and to maintain natural teeth. Osseointegration of implants
      would likely not be successful in these patients because the bone is abnormal and
      not well-vascularized.

PMID- 24933768
TI  - Concrescence: assessment of case by periapical radiography, cone beam computed
      tomography and micro-computed tomography.
AB  - The aim of this article was to describe imaging aspects of concrescence analyzed
      by three imaging modalities. A second molar joined together with a third molar
      was imaged using digital periapical radiography, cone beam computed tomography
      (CBCT) and micro-computed tomography (Micro-CT). On periapical radiograph, the
      mesial root of the third molar is superimposed on the distal root of the second
      molar. On CBCT images, a large cementum union between bulbous roots was detected,
      confirming the diagnosis of concrescence. On micro-CT images, the cementum union
      appeared limited to the apical third of the roots. In conclusion, both computed
      tomography modalities allowed for the diagnosis of concrescence. However, only
      micro-CT provided the real extension of the cementum union.

PMID- 24933770
TI  - Calcifying odontogenic cyst: dilemma in classification.
AB  - Calcifying odontogenic cyst (COC) shows extreme diversity in its clinical and
      histopathological features, as well as in its biological behavior. Because of
      this diversity, there has been confusion and disagreement on the terminology and
      classification of this lesion. Attempts to classify COC can be divided into two
      concepts: monistic and dualistic. We present a case of COC with coexisting
      histopathologic features of a cyst and a neoplasm, thus posing a dilemma in the
      terminology used to categorize and classify it.

PMID- 24933771
TI  - The relationship between estrogen, estrogen receptors and periodontal disease in
      adult women: a review of the literature.
AB  - The literature supports the fact that estrogen plays an important role in
      skeletal maintenance and remodeling. Estrogen, acting through estrogen receptors
      in the cells of the periodontal ligament, has a regulatory interaction on bone
      dynamics through a complex set of basic multicellular units (BMUs). Deficiency of
      estrogen results in an increased number of BMUs and enhanced bone turnover. The
      impact of the changes in estrogen deficiency on bone dynamics is primarily
      mediated through osteoclasts, with greater interdiction of estrogen's actions on
      trabecular bone than on cortical bone. The purpose of this manuscript is to
      review the literature for evidence to support an association between estrogen and
      periodontal disease in adult women, as well as bone mineral density, and to help
      clarify the mechanism of action. We found in our review of all pertinent
      databases, including Cochrane, that there are few peer-reviewed clinical studies
      that examine the relationship between estrogen deficiency and periodontal
      disease, and bone mineral density (BMD) and periodontal disease. Thus, future
      research is needed to investigate these associations so that at-risk patients can
      be identified earlier to avoid functional and esthetic sequellae of periodontal
      disease.

PMID- 24933772
TI  - An unusual affliction of the tongue.
AB  - A dramatic presentation of a large ulcer on the dorsal tongue of a recently
      hospitalized patient is presented. The lesion was found to be nosocomial in
      origin, and consistent with traumatic ulcerative granuloma with stromal
      eosinophilia (TUGSE). A review of the current pathogenic mechanisms, differential
      diagnosis and management of TUGSE is included.

PMID- 24933773
TI  - Effect of irrigation with Tetraclean on bacterial leakage of obturated root
      canals.
AB  - The purpose of the study presented here was to evaluate the effect of Tetraclean,
      Hypoclean, Chlor-XTRA, 2% chlorhexidine and 6% sodium hypochlorite/17% EDTA as a
      final irrigant on bacterial leakage of the root canal. One hundred and fifty-five
      extracted human maxillary central incisors were randomly divided into five
      experimental groups of 25 teeth each and two control groups of 15 teeth each. The
      root canals in each group were irrigated with 2 ml of the relevant irrigant
      between each filing. The root canals in group 5 were irrigated with 5 ml of 17%
      EDTA at the end of root canal preparation. The teeth in each group were obturated
      with gutta-percha and AH-26 sealer. Positive control teeth were obturated with a
      single gutta-percha cone without sealer, and negative controls were obturated in
      the same way as experimental groups. The coronal portion of each root was placed
      in contact with inoculum of Enterococcus faecalis in Brain Heart Infusion (BHI)
      culture media. Findings showed that the mean number of days for bacterial
      penetration in the Tetraclean group was greater than for other experimental
      groups. On the other hand, the Chlor-XTRA Vista group showed the fewest mean
      number of days for bacterial leakage.

PMID- 24933774
TI  - Anticipate & educate to navigate murky healthcare reform waters.

PMID- 24933775
TI  - Don't let depression derail your staff's morale and motivation.

PMID- 24933776
TI  - Managing yourself will help you manage others.

PMID- 24933777
TI  - Morale boosters can make your hospital a desirable place to work.

PMID- 24933778
TI  - Postanesthesia care 'action plan' aims to ensure optimal patient safety.

PMID- 24933779
TI  - Perceptive leadership fosters collaboration among hybrid OR staff.

PMID- 24933780
TI  - Smart and simple process changes help cut case times and costs.

PMID- 24933781
TI  - What happens in the BOD meetings doesn't stay there!

PMID- 24933782
TI  - Family caregivers as co-patients.

PMID- 24933783
TI  - Evaluating the impact of medication cabinets in patients' rooms on a medical
      surgical telemetry unit.
AB  - Results of a pre-post survey study designed to evaluate the impact of medication
      cabinets in patients' rooms on nurses' satisfaction with medication
      administration, medication charge accuracy, and errors are described.

PMID- 24933784
TI  - Mantra meditation as a bedside spiritual intervention.
AB  - The increased acceptance of integrative care allows nurses to investigate their
      role as active providers of spiritual care at the bedside. Lack of clear role
      expectations and interventions support the need for a simple, flexible spiritual
      bedside intervention. The use of a meditation mantra is discussed.

PMID- 24933785
TI  - Development and implementation of an educational support process for electronic
      nursing admission assessment documentation.
AB  - Educating nurses in use of the electronic health record nursing admission
      assessment using e-learning alone may not yield best results. Use of a hybrid
      instructional method of e-learning followed by a brief (20-minute) slide
      presentation with face-to-instruction significantly improved nursing
      documentation.

PMID- 24933786
TI  - Reducing nasal pressure ulcers with an alternative taping device.
AB  - Mucosal tissues are vulnerable to nasal pressure ulcers (NPUs) secondary to
      nasogastric tubes, and can cause hospital-associated complications and increased
      length of stay. The findings of this study suggest a commercially available
      device significantly reduces NPUs and is more adherent compared to conventional
      adhesive taping.

PMID- 24933787
TI  - Nonalcoholic fatty liver disease and the PNPLA3 gene.
AB  - Nonalcoholic fatty liver disease, a potentially fatal obesity-related condition,
      affects more than 70 million people in the United States. Nurses are well
      positioned to impact this genetically influenced disease by is increasing
      awareness, providing patient education, and advocating for affected persons.

PMID- 24933788
TI  - Procedure-specific postoperative pain management.
AB  - With 48 million surgical proceduces performed annually in the United States
      (Center for Disease Control and Prevention, 2012), posttoperative pain management
      is a significant health care concern for both patients and health care providers.
      Current information regarding assessment and treatment of postoperative pain is
      discussed, including recommendations from the Procedure-Specific Postoperative
      Pain Management (PROSPECT) working group.

PMID- 24933790
TI  - Statistical and clinical significance.

PMID- 24933789
TI  - Discharge planning rounds to the bedside: a patient- and family-centered
      approach.
AB  - Discharge planning rounds done at the bedside is an effective patient-centered
      approach to discharge planning and does not take any longer than traditional
      rounds apart from the patient and caregiver. Bedside rounds may decrease patient
      utilization of health care resources after discharge.

PMID- 24933791
TI  - The impact of simulation on patient care.

PMID- 24933792
TI  - A response to the transformation of America's health care: direct-care nurses
      bring FLOWERS to the bedside.

PMID- 24933793
TI  - Can there really be joy at work?

PMID- 24933794
TI  - Genetics: make the link.

PMID- 24933795
TI  - Disparities in multiple risk factors for cardiovascular diseases - Delaware,
      2011.
AB  - INTRODUCTION: The purpose of this study is to determine the prevalence of
      multiple risk factors for Cardiovascular Diseases (CVD) and to identify
      disparities in risk status among population subgroups in Delaware. As a secondary
      analysis the study will also analyze self-reported CVD prevalence overall and
      discuss differences in prevalence by age, sex, race/ethnicity, education, income,
      employment status, and county of residence. METHODS: Analysis was conducted using
      Delaware data for 4,777 respondents from the 2011 Behavioral Risk Factor
      Surveillance System (BRFSS). Survey participants having greater than or equal to
      two of the following risk factors: obesity, high blood pressure, high blood
      cholesterol, current smoking, and diabetes mellitus were considered as having
      multiple risk factors for CVD. RESULTS: In 2011, the prevalence of CVD in
      Delaware was 8.61 percent (95 percent Confidence Interval [CI, 7.55, 9.66]).
      Overall, 22.51 percent (95 percent CI, 20.62-24.40) of persons reported having no
      risk factors, 32.30 percent (95 percent CI, 30.31-34.28) reported one risk
      factor, and 45.20 percent (95 percent CI, 43.18-47.21) reported multiple risk
      factors. Prevalence of multiple risk factors was higher for the aged, less
      educated, and unemployed. Disparities by gender and race were not significant.
      Sussex County had a higher prevalence of CVD multiple risk factors, 53.18 percent
      (95 percent CI, 49.47-56.89) followed by Kent County, 49.75 percent (95 percent
      CI, 45.92-53.58). CONCLUSIONS: One of the priority goals of Healthy People 2020
      is to improve cardiovascular health and quality of life through prevention,
      detection, and treatment of risk factors for heart attack and stroke and also
      prevention of repeat cardiovascular events. This study indicates that in 2011 a
      higher proportion of the Delaware population had multiple risk factors for heart
      disease and stroke, particularly certain population subgroups defined by
      socioeconomic status. Development of effective prevention programs targeting
      populations with greater risk factor prevalence should reduce CVD incidence,
      which will significantly contribute to the decline in both CVD prevalence and CVD
      mortality. Understanding the determinants for modifiable risk factors might
      facilitate their control for public health.

PMID- 24933796
TI  - Benefits of a dentifrice containing 8% arginine, calcium carbonate, and sodium
      monofluorophosphate on enamel erosion.

PMID- 24933797
TI  - In vitro study of the effect of a dentifrice containing 8% arginine, calcium
      carbonate, and sodium monofluorophosphate on acid-softened enamel.
AB  - OBJECTIVE: To investigate the possible mode of action of a dentifrice containing
      8% arginine and calcium carbonate (Pro-Argin Technology), and sodium
      monofluorophosphate in delivering the benefits of preventing acid erosion and
      rehardening acid-softened enamel. METHODS: The surfaces of acid-softened bovine
      enamel specimens were evaluated after application of a dentifrice containing 8%
      arginine, calcium carbonate, and sodium monofluorophosphate in vitro. Scanning
      Electron Microscopy (SEM), Electronic Spectrometry for Chemical Analysis (ESCA),
      and Secondary Ion Mass Spectrometry (SIMS) were used to characterize the enamel
      surfaces. RESULTS: Exposure of pristine enamel surfaces to citric acid resulted
      in clear roughening of the surface. Multiple applications of a dentifrice
      containing 8% arginine, calcium carbonate, and sodium monofluorophosphate to the
      surface of the enamel resulted in the disappearance of the microscopic voids
      observed by SEM as a function of treatment applications. The ESCA analysis
      demonstrated that both the nitrogen and carbonate levels increased as the number
      of treatments increased, which provides evidence that arginine and calcium
      carbonate were bound to the surface. Observance of arginine's signature mass
      fragmentation pattern by SIMS analysis confirmed the identity of arginine on the
      enamel surface. CONCLUSION: A series of in vitro experiments has demonstrated a
      possible mode of action by which a dentifrice containing 8% arginine, calcium
      carbonate, and sodium monofluorophosphate delivers the benefits of preventing
      acid erosion and rehardening acid-softened enamel. The combination of arginine
      and calcium carbonate adheres to the enamel surface and helps to fill the
      microscopic gaps created by acid, which in turn helps repair the enamel and
      provides a protective coating against future acid attacks.

PMID- 24933798
TI  - Evaluation of a dentifrice containing 8% arginine, calcium carbonate, and sodium
      monofluorophosphate to prevent enamel loss after erosive challenges using an
      intra-oral erosion model.
AB  - OBJECTIVE: The objective of this study was to assess the ability of a dentifrice
      containing 8% arginine and calcium carbonate (Pro-Argin' Technology), and 1450
      ppm fluoride as sodium monofluorophosphate (MFP) to prevent enamel loss from an
      erosive acid challenge in comparison to a silica-based dentifrice with 1450 ppm
      fluoride as MFP using an intra-oral erosion model. METHODS: The intra-oral
      clinical study used a double blind, two-treatment, crossover design. A palatal
      retainer was used to expose the enamel specimens to the oral environment during
      the five-day treatment period. The retainer was designed to house three partially
      demineralized bovine enamel samples. The study population was composed of 24
      adults, ages 18 to 70 years. The study consisted of two treatment periods, with a
      washout period lasting seven (+/- three) days preceding each treatment phase. A
      silica-based dentifrice without fluoride was used during the washout period. The
      Test Dentifrice used in this study contained 8% arginine and calcium carbonate
      (Pro-Argin Technology), and 1450 ppm fluoride as sodium monofluorophosphate
      (MFP). The Control Dentifrice was silica-based and contained 1450 ppm fluoride as
      MFP. The treatment period lasted five days, during which the panelists wore the
      retainer 24 hours a day (except during meals and the ex vivo acid challenges) and
      brushed with their assigned product while wearing the retainer. The panelists
      brushed once in the morning and once in the evening each day for one minute,
      followed by a one-minute swish with the slurry and a rinse with 15 ml of water.
      The panelists brushed only their teeth and not the specimens directly. There were
      four ex vivo challenges with 1% citric acid dispersed throughout the day: two in
      the morning, one in the afternoon, and one in the evening. Mineral loss was
      monitored by a quantitative light fluorescence (QLF) technique. RESULTS: Twenty
      three of 24 subjects successfully completed the study. The one subject who did
      not complete the study did so for reasons unrelated to the study or products
      used. The average percent mineral loss for the Test Dentifrice and Control
      Dentifrice was 9.74 +/- 13.23 and 18.36 +/- 14.14, respectively. The statistical
      analysis showed that the observed product differences were statistically
      significant (p < 0.001). CONCLUSION: The Test Dentifrice with 8% arginine,
      calcium carbonate, and 1450 ppm fluoride as MFP provided significantly better
      protection against erosive challenges in comparison to the Control Dentifrice
      with 1450 ppm fluoride as MFP.

PMID- 24933800
TI  - Sodium fertilization increases termites and enhances decomposition in an
      Amazonian forest.
AB  - Added Na was used to determine whether litter decomposition and associated fungal
      biomass and termites are limited by Na availability in a lowland tropical
      rainforest at Yasuni, Ecuador. This is a partial test of the "sodium ecosystem
      respiration" (SER) hypothesis that posits Na is critical for consumers but not
      plants, that Na shortfall is more likely on highly weathered soils inland from
      oceanic aerosols, and that this shortfall results in decreased decomposer
      activity. We fertilized 4 x 4 m plots twice a month for a year with quantities of
      Na comparable to those falling on a coastal tropical rainforest. Decomposition
      rates of four substrates were consistently higher on +NaCl plots by up to 70% for
      cellulose, and 78%, 68%, and 29% for three woods of increasing percentage lignin.
      The density of termite workers averaged 17-fold higher on +NaCl plots; fungal
      biomass failed to differ. After controlling for temperature and precipitation,
      which co-limit gross primay productivity (GPP) and ecosystem respiration (ER),
      these results suggest that Na shortfall is an agent enhancing the storage of
      coarse woody debris in inland tropical forests.

PMID- 24933799
TI  - Evaluation of a dentifrice containing 8% arginine, calcium carbonate, and sodium
      monofluorophosphate to repair acid-softened enamel using an intra-oral
      remineralization model.
AB  - OBJECTIVE: An intra-oral remineralization study was conducted to compare the
      ability of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin
      Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP) to
      remineralize acid-softened bovine enamel specimens compared to a silica-based
      dentifrice with 1450 ppm fluoride as MFP. METHODS: The intra-oral clinical study
      employed a double blind, two-treatment, crossover design, and used an upper
      palatal retainer to expose the enamel specimens to the oral environment during
      product use and periods of remineralization. The retainer was designed to house
      three partially demineralized bovine enamel samples. The study population was
      comprised of 30 adults, ages 18 to 70 years. The study consisted of two treatment
      phases with a washout period lasting seven (+/- three) days preceding each
      treatment phase. A silica-based dentifrice without fluoride was used during the
      washout period. The Test Dentifrice used in this study contained 8% arginine,
      calcium carbonate, and 1450 ppm fluoride as sodium monofluorophosphate (MFP). The
      Control Dentifrice was silica-based and contained 1450 ppm fluoride as MFP. The
      treatment period consisted of a three-day lead-in period with the assigned
      product. The panelists brushed two times per day during the three-day lead-in
      period with the assigned product. On the fourth day, the panelists began brushing
      with the assigned product with the retainer in their mouth. The panelists brushed
      for one minute, followed by a one-minute swish with the slurry and a rinse with
      15 ml of water in the morning, in the afternoon, and night with the retainer in
      the mouth. The panelists brushed only their teeth and not the specimens directly.
      Changes in mineral content before and after treatment were measured using a Knoop
      microhardness tester. RESULTS: The results of the study showed that percent
      remineralization values for the Test Dentifrice and Control Dentifrice were
      14.99% and 8.66%, respectively. A statistical analysis showed that the Test
      Dentifrice was statistically significantly more effective at remineralizing acid
      softened enamel in comparison to the Control Dentifrice (p < 0.05). CONCLUSION:
      This study demonstrated that the Test Dentifrice with 8% arginine, calcium
      carbonate, and 1450 ppm fluoride as MFP is highly effective treatment for
      promoting remineralization of enamel that has been softened by an erosive
      challenge.

PMID- 24933801
TI  - Masting promotes individual- and population-level reproduction by increasing
      pollination efficiency.
AB  - Masting is a reproductive strategy defined as the intermittent and synchronized
      production of large seed crops by a plant population. The pollination efficiency
      hypothesis proposes that masting increases pollination success in plants. Despite
      its general appeal, no previous studies have used long-term data together with
      population- and individual-level analyses to assess pollination efficiency
      between mast and non-mast events. Here we rigorously tested the pollination
      efficiency hypothesis in ponderosa pine (Pinus ponderosa), a long-lived
      monoecious, wind-pollinated species, using a data set on 217 trees monitored
      annually for 20 years. Relative investment in male and female function by
      individual trees did not vary between mast and non-mast years. At both the
      population and individual level, the rate of production of mature female cones
      relative to male strobili production was higher in mast than non-mast years,
      consistent with the predicted benefit of reproductive synchrony on reproductive
      success. In addition, at the individual level we found a higher conversion of
      unfertilized female conelets into mature female cones during a mast year compared
      to a non-mast year. Collectively, parallel results at the population and
      individual tree level provide robust evidence for the ecological, and potentially
      also evolutionary, benefits of masting through increased pollination efficiency.

PMID- 24933802
TI  - Plant community response to loss of large herbivores differs between North
      American and South African savanna grasslands.
AB  - Herbivory and fire shape plant community structure in grass-dominated ecosystems,
      but these disturbance regimes are being altered around the world. To assess the
      consequences of such alterations, we excluded large herbivores for seven years
      from mesic savanna grasslands sites burned at different frequencies in North
      America (Konza Prairie Biological Station, Kansas, USA) and South Africa (Kruger
      National Park). We hypothesized that the removal of a single grass-feeding
      herbivore from Konza would decrease plant community richness and shift community
      composition due to increased dominance by grasses. Similarly, we expected grass
      dominance to increase at Kruger when removing large herbivores, but because large
      herbivores are more diverse, targeting both grasses and forbs, at this study
      site, the changes due to herbivore removal would be muted. After seven years of
      large-herbivore exclusion, richness strongly decreased and community composition
      changed at Konza, whereas little change was evident at Kruger. We found that this
      divergence in response was largely due to differences in the traits and numbers
      of dominant grasses between the study sites rather than the predicted differences
      in herbivore assemblages. Thus, the diversity of large herbivores lost may be
      less important in determining plant community dynamics than the functional traits
      of the grasses that dominate mesic, disturbance-maintained savanna grasslands.

PMID- 24933803
TI  - Does biodiversity protect humans against infectious disease?
AB  - Control of human infectious disease has been promoted as a valuable ecosystem
      service arising from the conservation of biodiversity. There are two commonly
      discussed mechanisms by which biodiversity loss could increase rates of
      infectious disease in a landscape. First, loss of competitors or predators could
      facilitate an increase in the abundance of competent reservoir hosts. Second,
      biodiversity loss could disproportionately affect non-competent, or less
      competent reservoir hosts, which would otherwise interfere with pathogen
      transmission to human populations by, for example, wasting the bites of infected
      vectors. A negative association between biodiversity and disease risk, sometimes
      called the "dilution effect hypothesis," has been supported for a few disease
      agents, suggests an exciting win-win outcome for the environment and society, and
      has become a pervasive topic in the disease ecology literature. Case studies have
      been assembled to argue that the dilution effect is general across disease
      agents. Less touted are examples in which elevated biodiversity does not affect
      or increases infectious disease risk for pathogens of public health concern. In
      order to assess the likely generality of the dilution effect, we review the
      association between biodiversity and public health across a broad variety of
      human disease agents. Overall, we hypothesize that conditions for the dilution
      effect are unlikely to be met for most important diseases of humans. Biodiversity
      probably has little net effect on most human infectious diseases but, when it
      does have an effect, observation and basic logic suggest that biodiversity will
      be more likely to increase than to decrease infectious disease risk.

PMID- 24933804
TI  - Multiple mutualist effects: conflict and synergy in multispecies mutualisms.
AB  - Most organisms interact with multiple mutualistic species that confer different
      functional benefits, yet current conceptual frameworks do not fully address this
      complexity. A network approach considers multiple mutualistic interactions within
      a functional type and has been largely nonmechanistic, with little attention to
      the fitness consequences of specific interactions. Alternatively, consumer
      resource approaches have explicitly characterized the mechanisms and fitness
      consequences of resource exchange, but have not been extended to functionally
      divergent partners. First, we merge these approaches using graphical models to
      define the multiple mutualist effects (MMEs) that occur when a focal species has
      multiple partner mutualists. This approach mirrors food web research that has
      been advanced by studies of multiple predator effects as well as by detailed
      investigations of modules nested within larger networks. Second, we define the
      pathways through which a focal mutualist and two or more partner species could
      interact, reviewing examples of MMEs that span a range from positive to negative
      fitness effects. Third, given the potential for nonadditivity demonstrated by the
      existing literature, we pose new hypotheses for species-interaction outcomes by
      examining factors such as the extent of overlap in rewards exchanged among
      partners and their resulting network topologies. Our synthesis illustrates how
      the consideration of MMEs can improve the ability to predict the outcomes of
      losses or gains of mutualisms from ecosystems.

PMID- 24933805
TI  - Climate warming mediates negative impacts of rapid pond drying for three
      amphibian species.
AB  - Anthropogenic climate change will present both opportunities and challenges for
      pool-breeding amphibians. Increased water temperature and accelerated drying may
      directly affect larval growth, development, and survival, yet the combined
      effects of these processes on larvae with future climate change remain poorly
      understood. Increased surface temperatures are projected to warm water and
      decrease water inputs, leading to earlier and faster wetland drying. So it is
      often assumed that larvae will experience negative synergistic impacts with
      combined warming and drying. However, an alternative hypothesis is that warming
      induced increases in metabolic rate and aquatic resource availability might
      compensate for faster drying rates, generating antagonistic larval responses. We
      conducted a mesocosm experiment to test the individual and interactive effects of
      pool permanency (permanent vs. temporary) and water temperature (ambient vs. (+) 
      3 degrees C) on three anurans with fast-to-slow larval development rates (Great
      Basin spadefoot [Spea intermontana], Pacific chorus frog [Pseudacris regilla],
      and northern red-legged frog [Rana aurora]). We found that although tadpoles in
      warmed pools reached metamorphosis 15-17 days earlier, they did so with little
      cost (< 2 mm) to size, likely due to greater periphyton growth in warmed pools
      easing drying-induced resource competition. Warming and drying combined to act
      antagonistically on early growth (P = 0.06) and survival (P = 0.06), meaning the
      combined impact was less than the sum of the individual impacts. Warming and
      drying acted additively on time to and size at metamorphosis. These
      nonsynergistic impacts may result from cotolerance of larvae to warming and
      drying, as well as warming helping to offset negative impacts of drying. Our
      results indicate that combined pool warming and drying may not always be harmful
      for larval amphibians. However, they also demonstrate that antagonistic responses
      are difficult to predict, which poses a challenge to proactive conservation and
      management. Our study highlights the importance of considering the nature of
      multiple stressor interactions as amphibians are exposed to an increasing number
      of anthropogenic threats.

PMID- 24933806
TI  - Countryside biogeography of Neotropical reptiles and amphibians.
AB  - The future of biodiversity and ecosystem services depends largely on the capacity
      of human-dominated ecosystems to support them, yet this capacity remains largely
      unknown. Using the framework of countryside biogeography, and working in the Las
      Cruces system of Coto Brus, Costa Rica, we assessed reptile and amphibian
      assemblages within four habitats that typify much of the Neotropics: sun coffee
      plantations (12 sites), pasture (12 sites), remnant forest elements (12 sites),
      and a larger, contiguous protected forest (3 sites in one forest). Through
      analysis of 1678 captures of 67 species, we draw four primary conclusions. First,
      we found that the majority of reptile (60%) and amphibian (70%) species in this
      study used an array of habitat types, including coffee plantations and actively
      grazed pastures. Second, we found that coffee plantations and pastures hosted
      rich, albeit different and less dense, reptile and amphibian biodiversity
      relative to the 326-ha Las Cruces Forest Reserve and neighboring forest elements.
      Third, we found that the small ribbons of "countryside forest elements" weaving
      through farmland collectively increased the effective size of a 326-ha local
      forest reserve 16-fold for reptiles and 14-fold for amphibians within our 236-km2
      study area. Therefore, countryside forest elements, often too small for most
      remote sensing techniques to identify, are contributing -95% of the available
      habitat for forest-dependent reptiles and amphibians in our largely human
      dominated study region. Fourth, we found large and pond-reproducing amphibians to
      prefer human-made habitats, whereas small, stream-reproducing, and directly
      developing species are more dependent on forest elements. Our investigation
      demonstrates that tropical farming landscapes can support substantial reptile and
      amphibian biodiversity. Our approach provides a framework for estimating the
      conservation value of the complex working landscapes that constitute roughly half
      of the global land surface, and which are experiencing intensification pressure
      worldwide.

PMID- 24933807
TI  - Landscape context affects genetic diversity at a much larger spatial extent than
      population abundance.
AB  - Regional landscape context influences the fate of local populations, yet the
      spatial extent of this influence (called the "scale of effect") is difficult to
      predict. Thus, a major problem for conservation management is to understand the
      factors governing the scale of effect such that landscape structure surrounding a
      focal area is measured and managed at the biologically relevant spatial scale.
      One unresolved question is whether and how scale of effect may depend on the
      population response measured (e.g., abundance vs. presence/absence). If scales of
      effect differ across population outcomes of a given species, management based on
      one outcome may compromise another, further complicating conservation decision
      making. Here we used an individual-based simulation model to investigate how
      scales of effect of landscapes that vary in the amount and fragmentation of
      habitat differ among three population responses (local abundance,
      presence/absence, and genetic diversity). We also explored how the population
      response measured affects the relative importance of habitat amount and
      fragmentation in shaping local populations, and how dispersal distance mediates
      the magnitude and spatial scale of these effects. We found that the spatial scale
      most strongly influencing local populations depended on the outcome measured and
      was predicted to be small for abundance, medium-sized for presence/absence, and
      large for genetic diversity. Increasing spatial scales likely resulted from
      increasing temporal scales over which outcomes were regulated (with local genetic
      diversity being regulated over the largest number of generations). Thus, multiple
      generations of dispersal and gene flow linked local population patterns to
      regional population size. The effects of habitat amount dominated the effects of
      fragmentation for all three outcomes. Increased dispersal distance strongly
      reduced abundance, but not presence/absence or genetic diversity. Our results
      suggest that managing protected species at spatial scales based on population
      abundance data may ignore broader landscape effects on population genetic
      diversity and persistence, lending support to the importance of managing large
      buffers surrounding areas of conservation concern.

PMID- 24933809
TI  - Linking secondary structure of individual size distribution with nonlinear size
      trophic level relationship in food webs.
AB  - Existing individual size distribution (ISD) theories assume that the trophic
      level (TL) of an organism varies as a linear function of its log-transformed body
      size. This assumption predicts a power-law distribution of the ISD, i.e., a
      linear relationship between size and abundance in log space. However, the
      secondary structure of ISD (nonlinear dome shape structures deviating from a
      power-law distribution) is often observed. We propose a model that extends the
      metabolic theory to link the secondary structure of ISD to the nonlinear size-TL
      relationship. This model is tested with empirical data collected from a
      subtropical reservoir. The empirical ISD and size-TL relationships were
      constructed by FlowCAM imaging analysis and stable isotope analyses,
      respectively. Our results demonstrate that the secondary structure of ISD can be
      predicted from the nonlinear function of size-TL relationship and vice versa.
      Moreover, these secondary structures arise due to (1) zooplankton omnivory and
      (2) the trophic interactions within microbial food webs.

PMID- 24933808
TI  - Capital and income breeding: the role of food supply.
AB  - An aspect of life history that has seen increasing attention in recent years is
      that of strategies for financing the costs of offspring production. These
      strategies are often described by a continuum ranging from capital breeding, in
      which costs are met purely from endogenous reserves, to income breeding, in which
      costs are met purely from concurrent intake. A variety of factors that might
      drive strategies toward a given point on the capital-income continuum has been
      reviewed, and assessed using analytical models. However, aspects of food supply,
      including seasonality and unpredictability, have often been cited as important
      drivers of capital and income breeding, but are difficult to assess using
      analytical models. Consequently, we used dynamic programming to assess the role
      of the food supply in shaping offspring provisioning strategies. Our model is
      parameterized for a pinniped (one taxon remarkable for the range of offspring
      provisioning strategies that it illustrates). We show that increased food
      availability, increased seasonality, and, to a lesser extent, increased
      unpredictability can all favor the emergence of capital breeding. In terms of the
      conversion of energy into offspring growth, the shorter periods of care
      associated with capital breeding are considerably more energetically efficient
      than income breeding, because shorter periods of care are associated with a
      higher ratio of energy put into offspring growth to energy spent on parent and
      offspring maintenance metabolism. Moreover, no clear costs are currently
      associated with capital accumulation in pinnipeds. This contrasts with general
      assumptions about endotherms, which suggest that income breeding will usually be
      preferred. Our model emphasizes the role of seasonally high abundances of food in
      enabling mothers to pursue an energetically efficient capital-breeding strategy.
      We discuss the importance of offspring development for dictating strategies for
      financing offspring production.

PMID- 24933810
TI  - The sexual neighborhood through time: competition and facilitation for
      pollination in Lobelia cardinalis.
AB  - Reproductive success in flowering plants is influenced by the morphology and
      timing of reproductive structures as well as the density of surrounding
      conspecifics. In species with separate male and female flower phases, successful
      pollen transfer is also expected to vary with the density and ratio of
      surrounding male and female flowers. Increased density of surrounding flowers may
      increase pollinator visitation rates, but the densities of male and female
      flowers will determine the availability of pollen and the strength of competition
      for pollen receipt. Here we (1) quantify the influence of surrounding plant
      density on total seasonal fruit and seed production, (2) quantify the influence
      of sexual neighborhood (surrounding sex ratio and densities of male- and female
      phase flowers) on fruit and seed production for individual flowers presented
      within the season, and (3) compare the influence of plant density on fitness to
      that of focal plant phenotype, specifically stigma-nectary distance and plant
      height, in a natural population of the pollen-limited, hummingbird-pollinated
      hermaphrodite Lobelia cardinalis. These relationships were examined at four
      spatial scales (10, 20, 50, and 100 cm). By examining temporal and spatial scales
      we found that (1) total seed production per plant decreased with increasing plant
      density at the smallest scale but increased with increasing density at all larger
      scales; (2) at any given time, a female-phase flower benefited from a higher
      density of surrounding male-phase flowers and a lower density of surrounding
      female-phase flowers; (3) when sex ratio was explicitly analyzed, a female-phase
      flower benefited from a lower proportion of surrounding female flowers as well as
      a lower total flower density; and (4) at the whole-plant level, taller plants
      were more likely to produce fruit (even when accounting for total number of
      flowers produced), consistent with pollinator preference for taller floral
      displays. Our results suggest that the local density of male and female flowers
      (and surrounding sex ratio) influences successful pollen transfer, implying that
      the local floral environment may shape how attraction traits like plant height
      are related to fitness.

PMID- 24933811
TI  - Quantifying invasion resistance: the use of recruitment functions to control for
      propagule pressure.
AB  - Invasive species distributions tend to be biased towards some habitats compared
      to others due to the combined effects of habitat-specific resistance to invasion
      and non-uniform propagule pressure. These two factors may also interact, with
      habitat resistance varying as a function of propagule supply rate. Recruitment
      experiments, in which the number of individuals recruiting into a population is
      measured under different propagule supply rates, can help us understand these
      interactions and quantify habitat resistance to invasion while controlling for
      variation in propagule supply rate. Here, we constructed recruitment functions
      for the invasive herb Hieracium lepidulum by sowing seeds at five different
      densities into six different habitat types in New Zealand's Southern Alps
      repeated over two successive years, and monitored seedling recruitment and
      survival over a four year period. We fitted recruitment functions that allowed us
      to estimate the total number of safe sites available for plants to occupy, which
      we used as a measure of invasion resistance, and tested several hypotheses
      concerning how invasion resistance differed among habitats and over time. We
      found significant differences in levels of H. lepidulum recruitment among
      habitats, which did not match the species' current distribution in the landscape.
      Local biotic and abiotic characteristics helped explain some of the between
      habitat variation, with vascular plant species richness, vascular plant cover,
      and light availability, all positively correlated with the number of safe sites
      for recruitment. Resistance also varied over time however, with cohorts sown in
      successive years showing different levels of recruitment in some habitats but not
      others. These results show that recruitment functions can be used to quantify
      habitat resistance to invasion and to identify potential mechanisms of invasion
      resistance.

PMID- 24933812
TI  - Drought induces spruce beetle (Dendroctonus rufipennis) outbreaks across
      northwestern Colorado.
AB  - This study examines influences of climate variability on spruce beetle
      (Dendroctonus rufipennis) outbreak across northwestern Colorado during the period
      1650 2011 CE. Periods of broad-scale outbreak reconstructed using documentary
      records and tree rings were dated to 1843-1860, 1882-1889, 1931-1957, and 2004
      2010. Periods of outbreak were compared with seasonal temperature, precipitation,
      vapor pressure deficit (VPD), the Palmer Drought Severity Index (PDSI), and
      indices of ocean-atmosphere oscillation that include the El Nino Southern
      Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal
      Oscillation (AMO). Classification trees showed that outbreaks can be predicted
      most successfully from above average annual AMO values and above average summer
      VPD values, indicators of drought across Colorado. Notably, we find that spruce
      beetle outbreaks appear to be predicted best by interannual to multidecadal
      variability in drought, not by temperature alone. This finding may imply that
      spruce beetle outbreaks are triggered by decreases in host tree defenses, which
      are hypothesized to occur with drought stress. Given the persistence of the AMO,
      the shift to a positive AMO phase in the late 1990s is likely to promote
      continued spruce beetle disturbance.

PMID- 24933813
TI  - Does relatedness matter? Phylogenetic density-dependent survival of seedlings in
      a tropical forest.
AB  - A complex set of interactions among neighbors influences plant performance and
      community structure. Understanding their joint operation requires extensive
      information on species characteristics and individual performance. We evaluated
      first-year survival of 35719 tropical forest seedlings of 222 species and 15
      annual cohorts relative to the density of conspecific and heterospecific
      neighbors and the phylogenetic similarity of heterospecific neighbors. Neighbors
      were from two size classes, and size asymmetric interactions provided insight
      into likely mechanisms. Large heterospecific and conspecific neighbors reduced
      seedling survival equally, suggesting resource competition rather than host
      specific enemies as a mechanism. In contrast, much stronger negative conspecific
      effects were associated with seedling neighbors capable of limited resource
      uptake, suggesting shared pests rather than competition as the mechanism.
      Survival improved, however, near phylogenetically similar heterospecific
      neighbors, suggesting habitat associations shared among closely related species
      affect spatial patterns of performance. Improved performance near
      phylogenetically similar neighbors is an emerging pattern in the handful of
      similar studies.

PMID- 24933814
TI  - The importance of long-distance seed dispersal for the demography and
      distribution of a canopy tree species.
AB  - Long-distance seed dispersal (LDD) is considered a crucial determinant of tree
      distributions, but its effects depend on demographic processes that enable seeds
      to establish into adults and that remain poorly understood at large spatial
      scales. We estimated rates of seed arrival, germination, and survival and growth
      for a canopy tree species (Miliusa horsfieldii), in a landscape ranging from
      evergreen forest, where the species' abundance is high, to deciduous forest,
      where it is extremely low. We then used an individual-based model (IBM) to
      predict sapling establishment and to compare the relative importance of seed
      arrival and establishment in explaining the observed distribution of seedlings.
      Individuals in deciduous forest, far from the source population, experienced
      multiple benefits (e.g., increased germination rate and seedling survival and
      growth) from being in a habitat where conspecifics were almost absent. The net
      effect of these spatial differences in demographic processes was significantly
      higher estimated sapling establishment probabilities for seeds dispersed long
      distances into deciduous forest. Despite the high rate of establishment in this
      habitat, Miliusa is rare in the deciduous forest because the arrival of seeds at
      long distances from the source population is extremely low. Across the entire
      landscape, the spatial pattern of seed arrival is much more important than the
      spatial pattern of establishment for explaining observed seedling distributions.
      By using dynamic models to link demographic data to spatial patterns, we show
      that LDD plays a pivotal role in the distribution of this tree in its native
      habitat.

PMID- 24933815
TI  - Aboveground and belowground legacies of native Sami land use on boreal forest in
      northern Sweden 100 years after abandonment.
AB  - Human activities that involve land-use change often cause major transformations
      to community and ecosystem properties both aboveground and belowground, and when
      land use is abandoned, these modifications can persist for extended periods.
      However, the mechanisms responsible for rapid recovery vs. long-term maintenance
      of ecosystem changes following abandonment remain poorly understood. Here, we
      examined the long-term ecological effects of two remote former settlements,
      regularly visited for -300 years by reindeer-herding Sami and abandoned -100
      years ago, within an old-growth boreal forest that is considered one of the most
      pristine regions in northern Scandinavia. These human legacies were assessed
      through measurements of abiotic and biotic soil properties and vegetation
      characteristics at the settlement sites and at varying distances from them. Low
      intensity land use by Sami is characterized by the transfer of organic matter
      towards the settlements by humans and reindeer herds, compaction of soil through
      trampling, disappearance of understory vegetation, and selective cutting of pine
      trees for fuel and construction. As a consequence, we found a shift towards early
      successional plant species and a threefold increase in soil microbial activity
      and nutrient availability close to the settlements relative to away from them.
      These changes in soil fertility and vegetation contributed to 83% greater total
      vegetation productivity, 35% greater plant biomass, and 23% and 16% greater
      concentrations of foliar N and P nearer the settlements, leading to a greater
      quantity and quality of litter inputs. Because decomposer activity was also 40%
      greater towards the settlements, soil organic matter cycling and nutrient
      availability were further increased, leading to likely positive feedbacks between
      the aboveground and belowground components resulting from historic land use.
      Although not all of the activities typical of Sami have left visible residual
      traces on the ecosystem after 100 years, their low-intensity but long-term land
      use at settlement sites has triggered a rejuvenation of the ecosystem that is
      still present. Our data demonstrates that aboveground-belowground interactions
      strongly control ecosystem responses to historical human land use and that medium
      to long-term consequences of even low-intensity human activities must be better
      accounted for if we are to predict and manage ecosystems succession following
      land-use abandonment.

PMID- 24933816
TI  - The role of functional traits and individual variation in the co-occurrence of
      Ficus species.
AB  - The processes that structure assemblages of species in hyper-diverse genera, such
      as Ficus (Moraceae), are not well understood. Functional diversity of co
      occurring species can reveal evidence for assembly processes; however,
      intraspecific variation may weaken species-level patterns. We studied whether
      functional and phylogenetic diversity of Ficus species indicated the effects of
      spatial variation in filters associated with topography or niche partitioning
      related to resource use and biotic interactions. We also asked whether individual
      trait patterns supported species-level patterns. We studied six traits (leaf
      area, succulence, specific leaf area [SLA], maximum diameter breast high [dbh],
      fruit size, and latex exudation) for 22 Ficus species and 335 individuals > or =
      10 cm dbh on a 20-ha forest plot in China. We found that higher elevation was
      correlated to changes in mean and reduced diversity of five traits, possibly due
      to frequent disturbances at higher elevations that favored fast-growing, poorly
      defended species with high SLA. Maximum dbh showed phylogenetic conservatism but
      high diversity among co-occurring species, suggesting adult stature is an
      important axis of within-quadrat niche partitioning. At the individual level,
      trait patterns were qualitatively consistent but were stronger than species-level
      patterns, especially for the leaf traits with the greatest intraspecific
      variation (SLA and succulence). Individual-level SLA exhibited the strongest
      evidence for both traits among and within-quadrat niche partitioning and
      indicated elevational filtering. Local niche partitioning and elevational
      filtering likely play an important role in maintaining species and functional
      diversity in the most speciose genus at our study site. Our results highlight the
      importance of individual variation, as it may reveal otherwise obscured niche
      effects.

PMID- 24933817
TI  - How many seeds does it take to make a sapling?
AB  - Tall canopy trees produce many more seeds than do understory treelets, yet, on
      average, both classes of trees achieve the same lifetime fitness. Using
      concurrent data on seedfall (8 years) and sapling recruitment (12 years) from a
      long-established tree plot at the Cocha Cashu Biological Station in Peru, we show
      that a 40-m canopy tree must produce roughly 13 times the mass of seeds to
      generate a sapling as a 5-m understory treelet. Mature tree height accounted for
      41% of the variance in seed mass per sapling recruit in a simple univariate
      regression, whereas a multivariate model that included both intrinsic (seed mass,
      tree height, and dispersal mode) and extrinsic factors (sapling mortality as a
      surrogate for microsite quality) explained only 31% of the variance in number of
      seeds per sapling recruit. The multivariate model accounted for less variance
      because tall trees produce heavier seeds, on average, than treelets. We used
      "intact" (mostly dispersed) seeds to parameterize the response variable so as to
      reduce, if not eliminate, any contribution of conspecific crowding to the
      difference in reproductive efficiency between canopy trees and treelets.
      Accordingly, a test for negative density dependence failed to expose a
      relationship between density of reproductive trees in the population and
      reproductive efficiency (seed mass per recruit). We conclude that understory
      treelets, some of which produce only a dozen seeds a year, gain their per-seed
      advantage by failing to attract enemies a la Janzen-Connell, either in ecological
      or evolutionary time.

PMID- 24933818
TI  - Trait-mediated environmental filtering drives assembly at biogeographic
      transition zones.
AB  - Abiotic filtering is a major driver of gradients in the structure and functioning
      of ecosystems from the tropics to the poles. It is thus likely that environmental
      filtering is an important assembly process at the transition of biogeographical
      zones where many species occur at their range limits. Shifts in species
      abundances and association patterns along environmental gradients can be
      indicative of environmental filtering, which is predicted to be stronger in areas
      of high abiotic stress and to promote increased similarity of ecological
      characteristics among co-occurring species. Here we test these hypotheses for
      scleractinian corals along a broad latitudinal gradient in high-latitude eastern
      Australia, where corals occur at the margins of their ranges and environmental
      tolerances. We quantify variation in taxonomic, zoogeographic, and functional
      patterns combined with null model approaches and demonstrate systematic spatial
      variation in community structure and significant covariance of species abundance
      distributions and functional characteristics along the latitudinal gradient. We
      describe a strong biogeographic transition zone, consistent with patterns
      expected under abiotic filtering, whereby species are sorted along the
      latitudinal gradient according to their tolerances for marginal reef conditions.
      High-latitude coastal reefs are typified by widely distributed, generalist,
      stress-tolerant coral species with massive and horizontally spreading
      morphologies and by diminishing influence of tropical taxa at higher latitudes
      and closer to the mainland. Higher degree of ecological similarity among co
      occurring species than expected by chance supports the environmental filtering
      hypothesis. Among individual traits, the structural traits corallite size and
      colony morphology were filtered most strongly, suggesting that characteristics
      linked to energy acquisition and physical stability may be particularly important
      for coral survival in high-latitude environments. These findings highlight
      interspecific differences and species interactions with the environment as key
      drivers of community organization in biogeographic transition zones and support
      the hypothesis that environmental filters play a stronger role than biotic
      interactions in structuring ecological communities in areas of high abiotic
      stress.

PMID- 24933819
TI  - Habitat connectivity shapes urban arthropod communities: the key role of green
      roofs.
AB  - The installation of green roofs, defined here as rooftops with a shallow soil
      cover and extensive vegetation, has been proposed as a possible measure to
      mitigate the loss of green space caused by the steady growth of cities. However,
      the effectiveness of green roofs in supporting arthropod communities, and the
      extent to which they facilitate connectivity of these communities within the
      urban environment is currently largely unknown. We investigated the variation of
      species community composition (beta diversity) of four arthropod groups with
      contrasting mobility (Carabidae, Araneae, Curculionidae, and Apidae) on 40 green
      roofs and 40 extensively managed green sites on the ground in the city of Zurich,
      Switzerland. With redundancy analysis and variation partitioning, we (1)
      disentangled the relative importance of local environmental conditions, the
      surrounding land cover composition, and habitat connectivity on species community
      composition, (2) searched for specific spatial scales of habitat connectivity for
      the different arthropod groups, and (3) discussed the ecological and functional
      value of green roofs in cities. Our study revealed that on green roofs community
      composition of high-mobility arthropod groups (bees and weevils) were mainly
      shaped by habitat connectivity, while low-mobility arthropod groups (carabids and
      spiders) were more influenced by local environmental conditions. A similar but
      less pronounced pattern was found for ground communities. The high importance of
      habitat connectivity in shaping high-mobility species community composition
      indicates that these green roof communities are substantially connected by the
      frequent exchange of individuals among surrounding green roofs. On the other
      hand, low-mobility species communities on green roofs are more likely connected
      to ground sites than to other green roofs. The integration of green roofs in
      urban spatial planning strategies has great potential to enable higher
      connectivity among green spaces, so that eventually even communities of low
      mobility species become connected. Furthermore, improving the design of green
      roofs (composition and configuration of vegetation and soil types) could enhance
      the ecological value, particularly for low-mobility species.

PMID- 24933820
TI  - Circulation constrains the evolution of larval development modes and life
      histories in the coastal ocean.
AB  - The evolutionary pressures that drive long larval planktonic durations in some
      coastal marine organisms, while allowing direct development in others, have been
      vigorously debated. We introduce into the argument the asymmetric dispersal of
      larvae by coastal currents and find that the strength of the currents helps
      determine which dispersal strategies are evolutionarily stable. In a spatially
      and temporally uniform coastal ocean of finite extent, direct development is
      always evolutionarily stable. For passively drifting larvae, long planktonic
      durations are stable when the ratio of mean to fluctuating currents is small and
      the rate at which larvae increase in size in the plankton is greater than the
      mortality rate (both in units of per time). However, larval behavior that reduces
      downstream larval dispersal for a given time in plankton will be selected for,
      consistent with widespread observations of behaviors that reduce dispersal of
      marine larvae. Larvae with long planktonic durations are shown to be favored not
      for the additional dispersal they allow, but for the additional fecundity that
      larval feeding in the plankton enables. We analyzed the spatial distribution of
      larval life histories in a large database of coastal marine benthic invertebrates
      and documented a link between ocean circulation and the frequency of
      planktotrophy in the coastal ocean. The spatial variation in the frequency of
      species with planktotrophic larvae is largely consistent with our theory;
      increases in mean currents lead to a decrease in the fraction of species with
      planktotrophic larvae over a broad range of temperatures.

PMID- 24933821
TI  - Experimentally elevated levels of testosterone at independence reduce fitness in
      a territorial bird.
AB  - Environmental conditions and individual strategies in early life may have a
      profound effect on fitness. A critical moment in the life of an organism occurs
      when an individual reaches independence and stops receiving benefits from its
      relatives. Understanding the consequences of individual strategies at the time of
      independence requires quantification of their fitness effects. We explored this
      period in the Red Grouse (Lagopus lagopus scoticus). In this system, testosterone
      and parasite (Trichostrongylus tenuis) levels are known to influence survival and
      reproduction, the two key components of individual fitness. We experimentally and
      simultaneously manipulated testosterone and parasites at three levels (high,
      intermediate, and control levels for both factors) in 195 young males in five
      populations using a factorial experimental design. We explored the effects of our
      treatments on fitness by monitoring reproduction and survival throughout the life
      of all males and estimating lambda(ind), a rate-sensitive index of fitness.
      Parasite challenges increased the number of worms with a time lag, as previously
      found. However, we did not find significant effects of parasite manipulations on
      fitness, possibly because parasite abundance did not increase to harmful levels.
      Our hormone manipulation was successful at increasing testosterone at three
      different levels. Such increases in hormone levels decreased overall fitness.
      This was caused by reduced offspring production in the first breeding attempt
      rather than by any effect of the treatment on bird survival. Our results
      highlight that investing in high testosterone levels at independence, a strategy
      that might enhance short-term recruitment probability in territorial species such
      as Red Grouse, has a fitness cost, and can influence the resolution of the trade
      off between reproduction and survival later in life.

PMID- 24933822
TI  - Synergism and context dependency of interactions between arbuscular mycorrhizal
      fungi and rhizobia with a prairie legume.
AB  - Biotic interactions play primary roles in major theories of the distribution and
      abundance of species, yet the nature of these biotic interactions can depend upon
      the larger ecological community. Leguminous plants, for example, commonly
      associate with both arbuscular mycorrhizal fungi (AMF) and rhizobia bacteria, and
      the pairwise interactions may depend upon the presence or identity of the third
      partner. To determine if the dynamics of plant-AMF and plant-rhizobia
      interactions are affected by the alternate symbiont, we manipulated the presence
      and identity of each symbiont, as well as levels of the nutrients supplied by
      each symbiont (nitrogen and phosphorus), on the growth of prairie legume Amorpha
      canescens. We found strong synergistic effects of AMF and rhizobia inoculation on
      plant biomass production that were independent of nutrient levels. AMF and
      rhizobia responses were each influenced by the other, but not in the same
      direction. AMF infection increased root nodule number and mass, but rhizobia
      inoculation decreased AMF hyphal colonization of roots. The relative benefits of
      each combination of symbionts depended upon phosphorus level. The effect of
      nitrogen was also contingent on the biotic environment where nitrogen addition
      decreased nodulation, but this decrease was reduced with coinfection by AMF. Our
      results demonstrate a strong contingency on the co-occurrence of AMF and rhizobia
      for the long-term fitness of A. canescens, and suggest that the belowground
      community is critical for the success of this species in tallgrass prairies.

PMID- 24933823
TI  - Positive interactions between large herbivores and grasshoppers, and their
      consequences for grassland plant diversity.
AB  - Although the influence of positive interactions on plant and sessile communities
      has been well documented, surprisingly little is known about their role in
      structuring terrestrial animal communities. We evaluated beneficial interactions
      between two distantly related herbivore taxa, large vertebrate grazers (sheep)
      and smaller insect grazers (grasshoppers), using a set of field experiments in
      eastern Eurasian steppe of China. Grazing by large herbivores caused
      significantly higher grasshopper density, and this pattern persisted until the
      end of the experiment. Grasshoppers, in turn, increased the foraging time of
      larger herbivores, but such response occurred only during the peak of growing
      season (August). These reciprocal interactions were driven by differential
      herbivore foraging preferences for plant resources; namely, large herbivores
      preferred Artemisia forbs, whereas grasshoppers preferred Leymus grass. The
      enhancement of grasshopper density in areas grazed by large herbivores likely
      resulted from the selective consumption of Artemisia forbs by vertebrate grazers,
      which may potentially improve the host finding of grasshoppers. Likewise,
      grasshoppers appeared to benefit large herbivores by decreasing the cover and
      density of the dominant grass Leymus chinensis, which hampers large herbivores'
      access to palatable forbs. Moreover, we found that large herbivores grazing alone
      may significantly decrease plant diversity, yet grasshoppers appeared to mediate
      such negative effects when they grazed with large herbivores. Our results suggest
      that the positive, reciprocal interactions in terrestrial herbivore communities
      may be more prevalent and complex than previously thought.

PMID- 24933824
TI  - Cascading effects of insectivorous birds and bats in tropical coffee plantations.
AB  - The loss of apex predators is known to have reverberating consequences for
      ecosystems, but how changes in broader predator assemblages affect vital
      ecosystem functions and services is largely unknown. Predators and their prey
      form complex interaction networks, in which predators consume not only herbivores
      but also other predators. Resolving these interactions will be essential for
      predicting changes in many important ecosystem functions, such as the control of
      damaging crop pests. Here, we examine how birds, bats, and arthropods interact to
      determine herbivorous arthropod abundance and leaf damage in Costa Rican coffee
      plantations. In an exclosure experiment, we found that birds and bats reduced non
      flying arthropod abundance by -35% and -25%, respectively. In contrast, birds and
      bats increased the abundance of flying arthropods, probably by consuming spiders.
      The frequency of this intraguild predation differed between birds and bats, with
      cascading consequences for coffee shrubs. Excluding birds caused a greater
      increase in herbivorous arthropod abundance than excluding bats, leading to
      increased coffee leaf damage. Excluding bats caused an increase in spiders and
      other predatory arthropods, increasing the ratio of predators to herbivores in
      the arthropod community. Bats, therefore, did not provide benefits to coffee
      plants. Leaf damage on coffee was low, and probably did not affect coffee yields.
      Bird-mediated control of herbivores, however, may aid coffee shrubs in the long
      term by preventing pest outbreaks. Regardless, our results demonstrate how
      complex, cascading interactions between predators and herbivores may impact
      plants and people.

PMID- 24933825
TI  - Demographic responses to mercury exposure in two closely related Antarctic top
      predators.
AB  - Although toxic chemicals constitute a major threat for wildlife, their effects
      have been mainly assessed at the individual level and under laboratory
      conditions. Predicting population-level responses to pollutants in natural
      conditions is a major and ultimate task in ecological and ecotoxicological
      research. The present study aims to estimate the effect of mercury (Hg) levels on
      future apparent survival rates and breeding performances. We used a long-term
      data set (-10 years) and recently developed methodological tools on two closely
      related Antarctic top predators, the South Polar Skua Catharacta maccormicki from
      Adelie Land and the Brown Skua C. lonnbergi from the Kerguelen Archipelago. Adult
      survival rates and breeding probabilities were not affected by Hg levels, but
      breeding success in the following year decreased with increasing Hg levels.
      Although South Polar Skuas exhibited much lower Hg levels than Brown Skuas, they
      suffered from higher Hg-induced breeding failure. This species difference could
      be attributed to an interaction between Hg and other environmental perturbations,
      including climate change and a complex cocktail of pollutants. By including Hg
      dependent demographic parameters in population models, we showed a weak
      population decline in response to increasing Hg levels. This demographic decline
      was more pronounced in South Polar Skuas than in Brown Skuas. Hence, Hg exposure
      differently affects closely related species. The wide range of environmental
      perturbations in Antarctic regions could exacerbate the demographic responses to
      Hg levels. In that respect, we urge future population modeling to take into
      account the coupled effects of climate change and anthropogenic pollution to
      estimate population projections.

PMID- 24933826
TI  - Individual fitness and phenotypic selection in age-structured populations with
      constant growth rates.
AB  - Powerful multiple regression-based approaches are commonly used to measure the
      strength of phenotypic selection, which is the statistical association between
      individual fitness and trait values. Age structure and overlapping generations
      complicate determinations of individual fitness, contributing to the popularity
      of alternative methods for measuring natural selection that do not depend upon
      such measures. The application of regression-based techniques for measuring
      selection in these situations requires a demographically appropriate,
      conceptually sound, and observable measure of individual fitness. It has been
      suggested that Fisher's reproductive value applied to an individual at its birth
      is such a definition. Here I offer support for this assertion by showing that
      multiple regression applied to this measure and vital rates (age-specific
      survival and fertility rates) yields the same selection gradients for vital rates
      as those inferred from Hamilton's classical results. I discuss how multiple
      regressions, applied to individual reproductive value at birth, can be used
      efficiently to estimate measures of phenotypic selection that are problematic for
      sensitivity analyses. These include nonlinear selection, components of the
      opportunity for selection, and multilevel selection.

PMID- 24933827
TI  - Decline of ectomycorrhizal fungi following a mountain pine beetle epidemic.
AB  - Forest die-off caused by mountain pine beetle (MPB; Dendroctonus ponderosa) is
      rapidly transforming western North American landscapes. The rapid and widespread
      death of lodgepole pine (Pinus contorta) will likely have cascading effects on
      biodiversity. One group particularly prone to such declines associated with MPB
      are ectomycorrhizal fungi, symbiotic organisms that can depend on pine for their
      survival, and are critical for stand regeneration. We evaluated the indirect
      effects of MPB on above- (community composition of epigeous sporocarps) and
      belowground (hyphal abundance) occurrences of ectomycorrhizal fungi across 11
      forest stands. Along a gradient of mortality (0-82% pine killed), macromycete
      community composition changed; this shift was driven by a decrease in the species
      richness of ectomycorrhizal fungi. Both the proportion of species that were
      ectomycorrhizal and hyphal length in the soil declined with increased MPB-caused
      pine mortality; < 10% of sporocarp species were ectomycorrhizal in stands with
      high pine mortality compared with > 70% in stands without MPB attacks. The rapid
      range expansion of a native insect results not only in the widespread mortality
      of an ecologically and economically important pine species, but the effect of MPB
      may also be exacerbated by the concomitant decline of fungi crucial for recovery
      of these forests.

PMID- 24933828
TI  - Distinguishing between Levy walks and strong alternative models: comment.

PMID- 24933829
TI  - Distinguishing between Levy walks and strong alternative models: reply.

PMID- 24933831
TI  - Productivity variation persists in the NHS.

PMID- 24933830
TI  - The time to invest in leader training is now.

PMID- 24933832
TI  - David Bennett shaping the NHS of the future.

PMID- 24933833
TI  - Dawn of a new vision for imaging.

PMID- 24933834
TI  - Paperless working tearing up all that has gone before.

PMID- 24933835
TI  - The new rules of staff engagement.

PMID- 24933836
TI  - Technology NHS democracy is just a click away democratic accountability has
      result, the overwhelming.

PMID- 24933837
TI  - Interview: public health's moral maze.

PMID- 24933838
TI  - Patient experience: push past symptom mysteries.

PMID- 24933840
TI  - Barriers to a paperless NHS: are you ready for your screen test?

PMID- 24933839
TI  - Education: work together be two of a kind.

PMID- 24933841
TI  - Can boards clip paper?

PMID- 24933842
TI  - The World Stroke Organization and nursing.

PMID- 24933843
TI  - The sign of Leser-Trelat: is it really so?--for your eyes only.

PMID- 24933844
TI  - Xerosis cutis: a common predicament of Raynaud's disease.

PMID- 24933846
TI  - LUZU (luliconazole) 1% cream.

PMID- 24933845
TI  - Dermatologic manifestation of hyperandrogenism: a retrospective chart review.
AB  - Several studies have described a wide spectrum of hyperandrogenism diseases, many
      of which are difficult to distinguish from each other. In order to better
      understand diseases of hyperandrogenism, the authors performed a retrospective
      study of the cutaneous features and metabolic findings in women with
      hyperandrogenism. A retrospective chart analysis compiled by three dermatologists
      in both academic and private settings was performed, including patients
      presenting with > or = 2 manifestations of hyperandrogenism. Relevant
      dermatologic and associated manifestations and laboratory and imaging study
      findings were reviewed. Moderate to severe acne was the most common
      manifestation. Other common manifestations that patients first presented with
      include hirsutism, acanthosis nigricans, androgenic alopecia, and skin tags.
      Oligomenorrhea was the most common systemic presenting sign. Statistical analysis
      of various clinical markers revealed correlations with hyperandrogenemia.
      Acanthosis nigricans and hirsutism were found to be useful clinical markers for
      hyperandrogenism, whereas androgenic alopecia was not. This study provides some
      insights into the presentation and diverse manifestations seen in
      hyperandrogenism.

PMID- 24933847
TI  - EpiCeram.

PMID- 24933848
TI  - Addressing the role of human herpesviruses 6 and 7 in DRESS.

PMID- 24933849
TI  - Lucio's phenomenon and/or relapsing erythema necroticans.

PMID- 24933850
TI  - Palmoplantar papules and hyperkeratosis in a deaf man.
AB  - A 31-year-old man presented with a history of extensive thickened skin of the
      palms and soles since the age of 7. The patient reported difficulty in ambulating
      and in using his hands secondary to his skin condition and associated pain. He
      also reported being seen by numerous specialists in the past for his hands, feet,
      and fingernails. He tried various topical medications, none of which were
      successful in minimizing the lesions on the hands and feet. Pertinent review of
      systems was positive for complete deafness diagnosed at 9 months of age. The
      patient did not speak and used sign language to communicate. His family history
      was significant for two brothers, both of whom are deaf and who have a similar
      skin condition of their hands and feet, but with lesser severity than the
      patient. The patient had no other medical issues.

PMID- 24933851
TI  - Historical diagnosis and treatment. Epithelioma. 1910.

PMID- 24933852
TI  - Proliferative fasciitis in the abdominal region.
AB  - A 30-year old man with no trauma history presented to our department of
      dermatology with a 2-year history of abdominal painful masses. The spontaneous
      pain and tenderness in the abdominal region gradually worsened. Physical
      examination revealed 3 firm, irregular subcutaneous nodules measuring 1 x 0.5 cm,
      which were movable and unattached to the overlying skin. One of the nodules was
      ulcerated (Figure 1). Histopathologic examination showed spindle-shaped
      fibroblast cells intermingled with gangliocyte-like giant cells in the hypodermis
      with an infiltrate made of lymphocytes and histiocytes (Figure 2 and Figure 3).
      The immunohistochemical staining showed the negativity of the fusiform cells and
      the gangliocyte-like cells to anti-S100 protein and to anti-smooth muscle actin.

PMID- 24933853
TI  - Perianal giant condyloma acuminatum (Buschke-Lowenstein tumor).
AB  - A 50-year-old heterosexual, HIV-negative man presented with a giant anal
      condyloma (Figure). He had iron deficiency anemia, a slow-growing anal wart for
      many years, and intermittent bleeding and pruritus. Esophagogastroduodenoscopy
      and colonoscopy findings were normal. Endoscopic ultrasound of the anorectum
      showed no anal sphincter involvement, and computed tomography did not reveal any
      pelvic inguinal lymph nodes. Wide-staged excision was performed and the patient
      recovered well with resolution of symptoms and no local recurrence at 1-year
      follow-up. Final pathology confirmed human papillomavirus (HPV) 6 strain and a
      giant condyloma acuminatum with mild atypia and no malignancy. Further
      examination of his oropharynx showed additional small HPV lesions, which were
      removed locally.

PMID- 24933854
TI  - Aplastic anemia and Hoyeraal-Hreidarsson syndrome.
AB  - A 2-year-old girl patient was admitted with intractable diarrhea, respiratory
      infections, and seizures. She was the first child of the first-degree parents.
      She was born at term with a birth weight of 2300 g. Physical examination revealed
      weight 6800 g, height 76 cm, and head circumference 41 cm, below the third
      percentile. Findings included sparse and dull hair, nail dystrophy, and
      proximally located thumbs (Figure). Aphthous lesions were observed on the oral
      mucosa. Neurologic examination disclosed poor head control. She could not sit
      without support and had hyper-reactive deep tendon reflexes.

PMID- 24933855
TI  - Merkel cell carcinoma.
AB  - A 92-year-old man presented for evaluation with a 1-month history of a rapidly
      growing asymptomatic pink nodule on his forearm. Biopsy results of the lesion
      demonstrated pathology consistent with Merkel cell carcinoma (MCC).
      Immunohistochemical studies displayed positive cytoplasmic staining for
      cytokeratin AE1/AE3, positive dot-like perinuclear staining for cytokeratin-20,
      diffuse cytoplasmic staining for neuron specific enolase, and no significant
      staining for S-100. Subsequent positron emission tomography did not reveal
      evidence of metastatic disease. Wide excision of the lesion was performed along
      with a sentinel node biopsy of his left axilla. The sentinel nodes were negative
      for MCC. Adjuvant radiation treatment of the tumor site was provided because the
      pathologist noted MCC within 2 mm of the deep margin.

PMID- 24933856
TI  - Bilateral zosteriform extragenital lichen sclerosus.
AB  - A 35-year-old man presented with asymptomatic eruption on both forearms and lower
      aspects of the legs for 6 months. The lesions first appeared on his inner aspects
      of the wrist, the dorsal surface of the hands, and legs and progressed to involve
      proximal aspects of the extremities. There was no significant past history. On
      examination, multiple pearly white papules and depigmented atrophic plaques were
      found bilaterally on the flexors of the arms and the extensors of the legs. The
      lesions were arranged in a linear manner, following the lines of Blaschko
      (Figures 1 and 2). The surface of the atrophic plaques was notable for prominent
      telangiectasia, giving an erythematous appearance. The genitalia, oral cavity,
      palms, and soles were spared. Systemic examination was noncontributory. Lichen
      striatus and extragenital lichen sclerosus (ELS) were considered the differential
      diagnosis. Clinically, the age of the patient, the absence of scaling, and the
      presence of atrophic plaques and telangiectasia were in favor of ELS. A punch
      biopsy from an atrophic plaque was performed, and it revealed hyperkeratosis,
      atrophic epidermis, basal layer vacuolar degeneration, mild lymphocytic
      infiltration in the dermis, edema, and homogenization of collagen of the upper
      portion of the dermis (Figures 3 and Figure 4). Histopathologic findings were
      consistent with lichen sclerosus. A diagnosis of bilateral zosteriform ELS was
      made.

PMID- 24933857
TI  - Traumatic panniculitis in a Chinese woman.

PMID- 24933858
TI  - Rosacea: could topical azelaic acid and oral tetracyclines modify
      videocapillaroscopic pattern?

PMID- 24933859
TI  - A wraparound world.
AB  - Health care isn't just a system in itself. It's part of a community. Like any
      system, a community operates most effectively when all components work in tandem.

PMID- 24933860
TI  - The next generation of palliative care.
AB  - Creating a true continuum of care includes incorporating palliative care. For the
      first time, payment structures are aligning to support palliative care beyond the
      hospital

PMID- 24933862
TI  - Beyond buzzwords: two state hospital associations collaborate around big data.

PMID- 24933861
TI  - Moving toward population health.

PMID- 24933865
TI  - Connecting the continuum: number of hurdles keep mHealth from hitting its stride.

PMID- 24933864
TI  - On the road: hospitals rev up use of mobile care.

PMID- 24933863
TI  - Peer to peer: health systems consult on IT, adding diversification and building
      partnerships.

PMID- 24933867
TI  - Wait, don't wait: use the ICD-1O delay time wisely.

PMID- 24933866
TI  - Skimping on IT security is costly.
AB  - The data breach at Target last winter put a bright spotlight on IT security. With
      an increasingly mobile world, hospital leaders must ratchet up their protections.

PMID- 24933868
TI  - There you are! Tracking systems aid patient safety efforts.

PMID- 24933869
TI  - ACO or no?
AB  - Hospitals must weigh the benefits and perils before deciding if - and what kind
      of - an accountable care organization is right for them. An AHA survey found only
      75percent of hospitals participated in an ACO in 2013.

PMID- 24933870
TI  - A smarter patient room.
AB  - David Ruthven headed up conceptual design for a new patient room; one that fully
      integrates new technology. Will it be a prototype for hospitals in the future?

PMID- 24933872
TI  - Hospitalists' role in a value-driven organization.

PMID- 24933871
TI  - Hospital labs go under microscope.
AB  - Financial pressures are hitting hospital clinical labs on both the inpatient and
      outpatient sides. To control expenses, hospitals are teaming up to buy supplies,
      centralizing services and improving blood management.

PMID- 24933873
TI  - Mother and child reunion.

PMID- 24933874
TI  - 9th International Phytotechnology Society Conference, 11-14 September 2012,
      Hasselt University, Belgium.

PMID- 24933875
TI  - The effect of long-term Cd and Ni exposure on seed endophytes of Agrostis
      capillaris and their potential application in phytoremediation of metal
      contaminated soils.
AB  - We examined whether long-term Cd exposure leads to beneficial changes in the
      cultivable endophytic bacteria present in the seeds of Agrostis capillaris.
      Therefore the cultivable seed endophytes of Agrostis capillaris growing on a long
      term Cd/Ni-contaminated plot (Cd/Ni seeds) were compared with those originating
      from a non-contaminated plot (control seeds). We observed plant- and contaminant
      dependent effects on the population composition between control and Cd/Ni seeds.
      Also differences in phenotypic characteristics were found: endophytes from Cd/Ni
      seeds exhibited more ACC deaminase activity and production of siderophores and
      IAA, while endophytes from control seeds, very surprisingly, showed more metal
      tolerance. Finally, the 3 most promising seed endophytes were selected based on
      their metal tolerance and plant growth promoting potential, and inoculated in
      Agrostis capillaris seedlings. In case of non-exposed plants, inoculation
      resulted in a significantly improved plant growth; after inoculation of Cd
      exposed plants an increased Cd uptake was achieved without affecting plant
      growth. This indicates that inoculation of Agrostis with its seed endophytes
      might be beneficial for its establishment during phytoextraction and
      phytostabilisation of Cd-contaminated soils.

PMID- 24933876
TI  - Early response of willow to increasing silver concentration exposure.
AB  - This is a preliminary hydroponic study to test willow sensitivity to silver
      nitrate, a highly toxic chemical compound. We grew willow cuttings for a period
      of three weeks in the presence of increasing AgNO(3) concentrations and assessed
      the response in terms of growth and physiology. We found that AgNO(3) is
      generally extremely harmful to willow. AgNO(3) concentration as high as 0.027 muM
      may result in a significant reduction of biomass productivity and a decrease in
      stomatal conductance over the first week of exposure. However, willows seem able
      to adapt to high AgNO(3) concentrations on a longer timeline.

PMID- 24933877
TI  - Effects of rapeseed oil on the rhizodegradation of polyaromatic hydrocarbons in
      contaminated soil.
AB  - Plants have the ability to promote degradation of polycyclic aromatic
      hydrocarbons (PAHs) in contaminated soil by supporting PAH degrading
      microorganisms in the rhizosphere (rhizodegradation). The aim of this study was
      to evaluate if rapeseed oil increases rhizodegradation because various studies
      have shown that vegetable oils are able to act as extractants for PAHs in
      contaminated soils and therefore might increase bioavailability of PAHs for
      microbial degradation. In this study different leguminous and grass species were
      tested. The results suggested a significant impact of vegetable oil (1 and 3%
      w/w) on plant growth (decrease of plant height and biomass). The results of the
      pot experiment showed a decrease in the PAH content of the soil without amendment
      of rapeseed oil after six months. In soil amended with 1% and 3% of oil, there
      was no decrease in PAH content within this period. Although no enhancement of PAH
      degradation by plants could be measured in the bulk soil of the pot experiments,
      a rhizobox experiment showed a significant reduction of PAH content in the
      rhizosphere of alfalfa (Medicago sativa cv. Europe). Our investigations also
      showed significant differences in the degradation behaviour of the 16
      individually analysed PAHs.

PMID- 24933878
TI  - Effect of pyrolysis temperature on chemical and surface properties of biochar of
      rapeseed (Brassica napus L.).
AB  - The biochar is an important carbon-rich product that is generated from biomass
      sources through pyrolysis. Biochar (charcoal) can be both used directly as a
      potential source of solid biofuels and as soil amendments for barren lands. The
      aim of this study was investigate influence of pyrolysis temperature on the
      physicochemical properties and structure of biochar. The biochars were produced
      by pyrolysis of rapeseed (Brassica napus L.) using a fixed-bed reactor at
      different pyrolysis temperatures (400-700 degrees C). The produced biochars were
      characterized by proximate and elemental analysis, Brunauer-Emmett-Teller (BET)
      surface area, particle size distributions, scanning electron microscopy (SEM),
      Fourier transform infrared (FTIR) spectroscopy. The results showed that both
      chemical and surface properties of the biochars were significantly affected by
      the pyrolysis temperature. Aromatic hydrocarbons, hydroxyl and carbonyl compounds
      were the majority components of the biochar. The biochar obtained at 700 degrees
      C had a high fixed carbon content (66.16%) as well as a high heating value, and
      therefore it could be used as solid fuel, precursor in the activated carbons
      manufacture (specific surface area until 25.38 m(2) g(-1)), or to obtain category
      A briquettes.

PMID- 24933879
TI  - Phytoremediation of lead (Pb) and arsenic (As) by Melastoma malabathricum L. from
      contaminated soil in separate exposure.
AB  - This study was conducted to investigate the uptake of lead (Pb) and arsenic (As)
      from contaminated soil using Melastoma malabathricum L. species. The cultivated
      plants were exposed to As and Pb in separate soils for an observation period of
      70 days. From the results of the analysis, M. malabathricum accumulated
      relatively high range of As concentration in its roots, up to a maximum of 2800
      mg/kg. The highest accumulation of As in stems and leaves was 570 mg/kg of plant.
      For Pb treatment, the highest concentration (13,800 mg/kg) was accumulated in the
      roots of plants. The maximum accumulation in stems was 880 mg/kg while maximum
      accumulation in leaves was 2,200 mg/kg. Only small amounts of Pb were
      translocated from roots to above ground plant parts (TF < 1). However, a wider
      range of TF values (0.01-23) for As treated plants proved that the translocation
      of As from root to above ground parts was greater. However, the high capacity of
      roots to take up Pb and As (BF > 1) is indicative this plants is a good
      bioaccumulator for these metals. Therefore, phytostabilisation is the mechanism
      at work in M. malabathricum's uptake of Pb, while phytoextraction is the dominant
      mechanism with As.

PMID- 24933881
TI  - The phytoremediation potential of native plants on New Zealand dairy farms.
AB  - Ecological restoration of marginal land and riparian zones in agricultural
      landscapes in New Zealand enhances the provision of above-ground ecosystem
      services. We investigated whether native endemic plant assemblages have
      remediation potential, through modifying soil nutrient and trace element
      mobility. Analysis of native plant foliage in situ indicated that selective
      uptake of a range of commonly deficient trace elements including Zn, B, Cu, Mn
      and Co could provide a browse crop to avoid deficiencies of these elements in
      livestock, although some native plants may enhance the risk of Mo and Cd
      toxicity. Native plant rhizospheres were found to modify soil physico-chemistry
      and are likely to influence lateral and vertical fluxes of chemical elements in
      drainage waters. Native plants on marginal land in agricultural landscapes could
      add value to dairy production systems whilst helping to resolve topical
      environmental issues.

PMID- 24933880
TI  - Effect of salinity on zinc uptake by Brassica juncea.
AB  - Salinity is a major worldwide problem that affects agricultural soils and limits
      the reclamation of contaminated sites. Despite the large number of research
      papers published about salt tolerance in Brassica juncea L., there are very few
      accounts concerning the influence of salinity on the uptake of trace metals. In
      this study, B. juncea plants divided through soil sets comprising 0, 900 and 1800
      mg Zn kg(-1), were treated with solutions containing 0, 60 and 120 mmol L(-1) of
      NaCl, with the purpose of observing the effect of salt on Zn uptake, and some
      physiological responses throughout the 90 days experiment. Increasing
      concentrations of NaCl and Zn produced a decline in the ecophysiological and
      biochemical properties of the plants, with observable synergistic effects on
      parameters like shoot dry weight, leaf area, or photochemical efficiency.
      Nevertheless, plants treated with 60 mmol L(-1) of NaCl accumulated striking
      harvestable amounts of Zn per plant that largely exceed those reported for
      Thlaspi caerulescens. It was concluded that salinity could play an important role
      on the uptake of Zn by B. juncea. The potential mechanisms behind these results
      are discussed, as well as the implications for phytoremediation of Zn on saline
      and non-saline soils.

PMID- 24933882
TI  - Feasibility of labile Zn phytoextraction using enhanced tobacco and sunflower:
      results of five- and one-year field-scale experiments in Switzerland.
AB  - Phytoextraction with somaclonal variants of tobacco and sunflower mutant lines
      (non-GMs) with enhanced metal uptake and tolerance can be a sustainable
      alternative to conventional destructive decontamination methods, especially for
      stripping bioavailable zinc excess in topsoil. The overall results of a 5-year
      time series experiment at field scale in north-eastern Switzerland confirm that
      the labile Zn pool in soil can be lowered by 45-70%, whereas subplots without
      phytoextraction treatment maintained labile Zn concentrations. In 2011, the
      phytoextraction experiment site was enlarged by a factor of 3, and the labile 0.1
      M NaNO3 extractable Zn concentration in the soil was reduced up to 58% one period
      after harvest. A Mass Balance Analysis confirmed soil Zn decontamination in line
      with plant Zn uptake. The plants partially take Zn from the non-labile pool of
      the totaL The sustainability of Zn phytoextraction in subplots that no longer
      exceed the Swiss trigger value is now assessed over time. In contrary to the
      phytoextraction of total soil Zn which needs a long cleaning up time, the
      bioavailable Zn stripping is feasible within a few years period.

PMID- 24933883
TI  - Metal phytoremediation by the halophyte Limoniastrum monopetalum (L.) Boiss: two
      contrasting ecotypes.
AB  - The phytoremediation potential of the halophyte Limoniastrum monopetalum for the
      removal of Cd and Pb from polluted sites is assessed in this work. Two pot
      experiments were conducted; the first with wild L. monopetalum grown on soil
      polluted with Cd and Pb irrigated at different salinities, and the second with
      commonly cultivated ornamental L. monopetalum grown on soil polluted with Cd
      irrigated also at different salinities. The data revealed that wild L.
      monopetalum is a Cd and Pb tolerant plant able to accumulate at least 100 ppm of
      cadmium in its shoots without showing any significant decrease in terms of
      biomass production, chlorophyll content or water content suggesting that it could
      be an accumulator of Cd. Pb above-ground accumulation was kept at low levels with
      the majority of Pb localized in the roots. On the other hand, contrasting results
      were obtained for ornamental L. monopetalum which although it was found to be
      also Cd tolerant, Cd accumulation in its tissues was kept at significantly lower
      levels especially compared to that of the wild ecotype. In addition for
      ornamental L. monopetalum salinity did not have a positive effect on Cd
      accumulation and translocation as observed in the wild type and in other
      halophytes. Analysis of the salt excretion crystals on the leaf surface confirmed
      that wild and cultivated ornamental L. monopetalum excrete cadmium and lead
      through their salt glands as a possible metal detoxification mechanism, although
      the amount excreted by the ornamental L. monopetalum is significantly less.

PMID- 24933884
TI  - Rhizoremediation of diesel-contaminated soil with two rapeseed varieties and
      petroleum degraders reveals different responses of the plant defense mechanisms.
AB  - Plant-assisted bioremediation (rhizoremediation) stands out as a potential tool
      to inactivate or completely remove xenobiotics from the polluted environment.
      Therefore, it is of key importance to find an adequate combination of plant
      species and microorganisms that together enhance the clean-up process. To
      understand the response of plants upon bioaugmentation, the antioxidative and
      detoxification system was analyzed in high and low erucic acid rapeseed varieties
      (HEAR and LEAR, respectively), after 8 weeks of their treatment with petroleum
      degraders and 6000 mg diesel oil/kg dry soil. The oxidative stress was enhanced
      in LEAR being exposed to sole diesel oil, in comparison with HEAR. However, when
      LEAR plants were additionally inoculated with bacteria, suppression of total
      catalase (CAT) and ascorbate peroxidase (APX) activity were observed.
      Interestingly, glutathione transferase (GST) activity was found in these plants
      at a much higher level than in HEAR, which correlated with a more efficient
      diesel removal performed by LEAR in the polluted soil and upon bioaugmentation. A
      distinct profile of polycyclic aromatic hydrocarbons (PAH) was detected in leaves
      of these plants. Neither LEAR nor HEAR experienced any changes in the
      photosynthetic capacity upon diesel pollution and presence of petroleum
      degraders, which supports the usefulness of rhizoremediation with rapeseed.

PMID- 24933885
TI  - Phytoremediation of cadmium-contaminated soils by young Douglas fir trees:
      effects of cadmium exposure on cell wall composition.
AB  - Douglas fir trees grown on an artificially Cd-contaminated soil, can tolerate
      this trace element (up to 68 mg/kg in soil) during several months. Most of the
      absorbed Cd is retained in roots (25 mg/kg DM), but transfer to aerial part is
      also effective. Showing the highest content, up to 6 mg/kg DM, among all the
      aboveground parts, barks seem to be a preferred storage compartment. However, the
      transfer factor is quite low, about 0.3. Another objective of this study was to
      compare the cell wall components of trees exposed to increasing Cd amounts in
      soil. A decrease in lignin and an increase in pectin contents were observed in
      response to increasing soil cadmium concentration. A concurrent reduction in
      methyl-esterification of pectin suggests than the structure of this major binding
      site could therefore be modified as a reaction to cadmium contamination. Future
      prospects will focus on the modulation of pectin composition in response to Cd
      exposure.

PMID- 24933886
TI  - Arsenic uptake and translocation by plants in pot and field experiments.
AB  - A work undertaken by pot and field experiments to assess the suitability of
      poplars and ferns for the in-situ, phytoextraction, of a dumping site with
      residues from the roasting process of arseno-pyrite is reported. The main
      characteristic of this site is the high content of both the As metalloid and
      heavy metals (e.g., Al, Fe, Cu, Co, Cr, Pb). Two poplar clones (Populus deltoides
      'Dvina' and Populus x canadensis 'Orion') and Pteris vittata (Chinese brake fern)
      were planted in the contaminated soil both ex situ in pots and in situ. Plant
      survival, As accumulation in plant tissues, leaf content of pigments, soluble
      proteins, activity of catalase and SH-groups in both roots and leaves were
      evaluated during a 24-month study period. Both poplar and fern plants exhibited
      an increase in the activity of catalase and SH group contents when grown in the
      presence of pyrite ashes. The results showed that the co-planting system (arsenic
      hyperaccumulator fern Pteris vittata and Populus clones) was suitable for
      phytoextraction of multi-contaminated dumping sites. Agronomic measures such as
      irrigation, soil tillage and amendments also seem to be necessary for the
      successful establishment of poplar trees and ferns in contaminated soils in order
      to enhance plant growth through the improvement of soil conditions.

PMID- 24933887
TI  - Influence of plant root exudates on the mobility of fuel volatile compounds in
      contaminated soils.
AB  - Vegetation and its associated microorganisms play an important role in the
      behaviour of soil contaminants. One of the most important elements is root
      exudation, since it can affect the mobility, and therefore, the bioavailability
      of soil contaminants. In this study, we evaluated the influence of root exudates
      on the mobility of fuel derived compounds in contaminated soils. Samples of humic
      acid, montmorillonite, and an A horizon from an alumi-umbric Cambisol were
      contaminated with volatile contaminants present in fuel: oxygenates (MTBE and
      ETBE) and monoaromatic compounds (benzene, toluene, ethylbenzene and xylene).
      Natural root exudates obtained from Holcus lanatus and Cytisus striatus and ten
      artificial exudates (components frequently found in natural exudates) were added
      to the samples, individually and as a mixture, to evaluate their effects on
      contaminant mobility. Fuel compounds were analyzed by headspace-gas
      chromatography-mass spectrometry. In general, the addition of natural and
      artificial exudates increased the mobility of all contaminants in humic acid. In
      A horizon and montmorillonite, natural or artificial exudates (as a mixture)
      decreased the contaminant mobility. However, artificial exudates individually had
      different effects: carboxylic components increased and phenolic components
      decreased the contaminant mobility. These results established a base for
      developing and improving phytoremediation processes of fuel-contaminated soils.

PMID- 24933888
TI  - Phytoprotective effect of arbuscular mycorrhizal fungi species against arsenic
      toxicity in tropical leguminous species.
AB  - Arbuscular mycorrhizal fungi (AMF) improve the tolerance of hosting plants to
      arsenic (As) in contaminated soils. This work assessed the phytoprotective effect
      of Glomus etunicatum, Acaulospora morrowiae, Gigaspora gigantea, and Acaulospora
      sp. on four leguminous species (Acacia mangium, Crotalaria juncea, Enterolobium
      contortisiliquum, and Stizolobium aterrimum) in an As-contaminated soil from a
      gold mining area. AMF root colonization, biomass production, As and P
      accumulation, as well as arsenic translocation index (TI) from roots to shoots
      were measured. The AMF phytoprotective effect was assessed by the P/As ratio and
      the activity of plant antioxidant enzymes. The AMF colonization ranged from 24 to
      28%. In general, all leguminous species had low As TI when inoculated with AMF
      species. Inoculation of C. juncea with Acaulospora sp. improved significantly As
      accumulation in roots, and decreased the activity of ascorbate peroxidase (APX)
      and superoxide dismutase (SOD), highlighting its phytoprotective effect and the
      potential use of this symbiosis for phytoremediation of As-contaminated soils.
      However, S. aterrimum has also shown a potential for phytoremediation
      irrespectively of AMF inoculation. APX was a good indicator of the
      phytoprotective effect against As contamination in C. juncea and A. mangium. In
      general P/As ratio in shoots was the best indicator of the phytoprotective effect
      of all AMF species in all plant species.

PMID- 24933889
TI  - Constructed wetlands for tannery wastewater treatment in Portugal: ten years of
      experience.
AB  - Wastewaters from tannery industry are complex in composition and providing
      adequate treatment can be difficult. Constructed wetlands (CW) are regarded as an
      alternative treatment to the conventional biological systems, as a developing
      cost-effective and environmentally friendly phytoremediation technology. The
      present review compiles and integrates information on CWs technology for the
      needs of the tannery sector. The following issues arise as crucial for the
      implementation of such systems, namely i) an accurate wastewater characterization
      and an effective pretreatment before reaching the CW, ii) choosing the plants
      species better adapted to the imposed conditions, iii) substrate selection and
      iv) range of organic loadings applied. The examples practiced in Portugal give
      indication that horizontal subsurface flow systems, with expanded clay media, are
      a suitable option to be considered when dealing with high organic loading tannery
      wastewater (up to c.a. 3800 kgCODha(-1)d(-1)), being resilient to a wide range of
      hydraulic variations. Plants such as Phragmites and Typha have shown to be
      adequate for tannery wastewater depuration, with Arundo donax proving resilient
      to high salinity wastewaters. The flexibility of implementation allows the CW to
      be adapted to different sites with different configurations, being suitable as
      main secondary or tertiary treatment stage.

PMID- 24933890
TI  - Plant communities in multi-metal contaminated soils: a case study in the National
      Park of Alta Murgia (Apulia region - Southern Italy).
AB  - A phytosociological study was conducted in the National Park of Alta Murgia in
      the Apulia region (Southern Italy) to determine the adverse effects of metal
      contamination of soils on the distribution of plant communities. The
      phytosociological analyses have shown a na, remarkable biodiversity of vegetation
      on non-contaminated soils, while biodiversity appeared strongly reduced on metal
      contaminated soils. The area is naturally covered by a wide steppic grassland
      dominated by Stipa austroitalica Martinovsky subsp, austroitalica. Brassicaceae
      such as Sinapis arvensis L. are the dominating species on moderated contaminated
      soils, whereas spiny species of Asteraceae such as Silybum marianum (L.) Gaertn.
      and Carduus pycnocephalus L. subsp, pycnocephalus are the dominating vegetation
      on heavily metal-contaminated soils. The presence of these spontaneous species on
      contaminated soils suggest their potential for restoration of degraded lands by
      phytostabilization strategy.

PMID- 24933891
TI  - Adsorption optimization of lead (II) using Saccharum bengalense as a non
      conventional low cost biosorbent: isotherm and thermodynamics modeling.
AB  - In the present study a novel biomass, derived from the pulp of Saccharum
      bengalense, was used as an adsorbent material for the removal of Pb (II) ions
      from aqueous solution. After 50 minutes contact time, almost 92% lead removal was
      possible at pH 6.0 under batch test conditions. The experimental data was
      analyzed using Langmuir, Freundlich, Timken and Dubinin-Radushkevich two
      parameters isotherm model, three parameters Redlich-Peterson, Sip and Toth models
      and four parameters Fritz Schlunder isotherm models. Langmuir, Redlich-Peterson
      and Fritz-Schlunder models were found to be the best fit models. Kinetic studies
      revealed that the sorption process was well explained with pseudo second-order
      kinetic model Thermodynamic parameters including free energy change (AG degrees),
      enthalpy change (AH degrees) and entropy change (AS degrees) have been calculated
      and reveal the spontaneous, endothermic and feasible nature of the adsorption
      process. The thermodynamic parameters of activation (deltaG(#), deltaH(#) and
      deltaS(#)) were calculated from the pseudo-second order rate constant by using
      the Eyring equation. Results showed that Pb (II) adsorption onto SB is an
      associated mechanism and the reorientation step is entropy controlled.

PMID- 24933892
TI  - Phytoremediation of abandoned crude oil contaminated drill sites of Assam with
      the aid of a hydrocarbon-degrading bacterial formulation.
AB  - Environmental deterioration due to crude oil contamination and abandoned drill
      sites is an ecological concern in Assam. To revive such contaminated sites,
      afield study was conducted to phytoremediate four crude oil abandoned drill sites
      of Assam (Gelakey, Amguri, Lakwa, and Borholla) with the aid of two hydrocarbon
      degrading Pseudomonas strains designated N3 and N4. All the drill sites were
      contaminated with 15.1 to 32.8% crude oil, and the soil was alkaline in nature
      (pH8.0-8.7) with low moisture content, low soil conductivity and low activities
      of the soil enzymes phosphatase, dehydrogenase and urease. In addition, N, P, K,
      and C contents were below threshold limits, and the soil contained high levels of
      heavy metals. Bio-augmentation was achieved by applying Pseudomonas aeruginosa
      strains N3 and N4 followed by the introduction of screened plant species Tectona
      grandis, Gmelina arborea, Azadirachta indica, and Michelia champaca. The findings
      established the feasibility of the phytoremediation of abandoned crude oil
      contaminated drill sites in Assam using microbes and native plants.

PMID- 24933893
TI  - Susceptibility of riparian wetland plants to perfluorooctanoic acid (PFOA)
      accumulation.
AB  - As plants have been shown to accumulate organic compounds from contaminated
      sediments, there is a potential for long-lasting ecological impact as a result of
      contaminant accumulation in riparian areas of wetlands, particularly the
      accumulation of non-biodegradable contaminants such as perfluorooctanoic acid
      (PFOA). In this study, commonly found riparian wetland plants including reeds,
      i.e., Xanthium strumarium, Phragmites australis, Schoenoplectus corymbosus,
      Ruppia maritime; Populus canescens, Polygonum salicifolium, Cyperus congestus;
      Persicaria amphibian, Ficus carica, Artemisia schmidtiana, Eichhornia crassipes,
      were studied to determine their susceptibility to PFOA accumulation from PFOA
      contaminated riparian sediment with a known PFOA concentration, using liquid
      chromatography/tandem mass spectrometry (LC/MS/MS). The bioconcentration factor
      (BCF) indicated that the plants affinity to PFOA accumulation was; E. crassipes,
      > P. sali-cifolium, > C. congestus, > P. x canescens, > P. amphibian, > F.
      carica, > A. schmidtiana, > X. strumarium,> P. australis, > R. maritime, > S.
      corymbosus. The concentration of PFOA in the plants and/or reeds was in the range
      11.7 to 38 ng/g, with a BCF range of 0.05 to 0.37. The highest BCF was observed
      in sediment for which its core water had a high salinity, total organic carbon
      and a pH which was near neutral. As the studied plants had a higher affinity for
      PFOA, the resultant effect is that riparian plants such as E. crassipes, X.
      strumarium, and P. salicifolium, typified by a fibrous rooting system, which grow
      closer to the water edge, exacerbate the accumulation of PFOA in riparian
      wetlands.

PMID- 24933894
TI  - Characterization of transgenic tobacco plants containing bacterial bphC gene and
      study of their phytoremediation ability.
AB  - Genetically modified plants can serve as an efficient tool for remediation of
      diverse dangerous pollutants of the environment such as pesticides, heavy metals,
      explosives and persistent organic compounds. Transgenic lines of Nicotiana
      tabacum containing bacterial bphC gene from the degradation pathway of
      polychlorinated biphenyls (PCBs) were tested. The product of the bphC gene -
      enzyme 2,3-dihydroxybiphenyl-1,2-dioxygenase is responsible for cleaving of the
      biphenyl ring. The presence of bphC gene in transgenic plants was detected on
      DNA, RNA and protein level. The expression of the bphC/His gene was verified
      afterpurification of the enzyme from plants by affinity chromatography followed
      by a Western blot and immunochemical assay. The enzyme activity of isolated
      protein was detected. Efficient transformation of 2,3-DHB by transgenic plants
      was achieved and the lines also exhibited high production of biomass. The
      transgenic plants were more tolerant to the commercial PCBs mixture Delor 103
      than non-transgenic tobacco. And finally, the higher decrease of total PCB
      content and especially congener 28 in real contaminated soil from a dumpsite was
      determined after cultivation of transgenic plant in comparison with nontransgenic
      tobacco. The substrate specificity of transgenic plants was the same as substrate
      specificity of BphC enzyme.

PMID- 24933895
TI  - Accumulation and response of willow plants exposed to environmental relevant
      sulfonamide concentrations.
AB  - As a result of manure application to arable lands, agricultural ecosystems are
      often contaminated by veterinary antibiotics. In this study the aptitude of Salix
      fragilis L. to accumulate and tolerate sulfadimethoxine (SDM) was evaluated,
      together with the antibiotic effects on the plant development, with particular
      attention focused on roots. Results showed an antibiotic presence in root
      tissues, but not in leaves, after one month of SDM exposure to 0.01, 0.1, 1 and
      10 mg l(-1). A hormetic growth of the hypogeal system was observed, however
      stress symptoms on the root development were only noticed after treatment to the
      highest dose. Results obtained from a second test, where new cuttings were
      exposed to 10 mg SDM l(-1) for different periods, suggested that willow tolerance
      to SDM increased with the exposure duration, probably because of the onset of
      particular acclimation mechanisms. Therefore, the present work indicates that
      this woody species could be utilized in the phytoremediation of sulfonamide
      antibiotics at doses comparable to that found in agricultural ecosystems once
      obtained appropriate confirmations through future studies at a laboratory and
      field scale.

PMID- 24933896
TI  - Leucanthemum vulgare lam. germination, growth and mycorrhizal symbiosis under
      crude oil contamination.
AB  - Oil contamination of soil limits plants' access to water and nutrients.
      Leucanthemum vulgare colonized by mycorrhizae could provide an effective tool in
      remedying oil contamination. Seeds of L. vulgare were planted in pots containing
      soil mixed with petroleum at 0, 2.5, 5, 7.5, and 10% w/w and propagules of
      mycorrhizal fungi. Plants were grown under ambient conditions for 16 weeks. Seed
      germination data were collected weekly for three weeks. Mycorrhizal percentage,
      spore counts, length and weight of roots and shoots were determined after
      harvesting. Results showed significant differences in seed germination rates
      between oil-treated, mycorrhizal and non-mycorrhizal plants. The overall
      germination rate was greater at 7.5% w/w crude oil contamination (p = 0.05) in
      mycorrhizal and non-mycorrhizal pots with significant differences between their
      respective Root:Shoot ratios (both length and weight). Results of this research
      showed L. vulgare could be germinated and grown in crude oil contaminated soils
      and could be used to augment plant establishment as part of phytoremediation
      practices.

PMID- 24933897
TI  - Adaptive long-term monitoring of soil health in metal phytostabilization:
      ecological attributes and ecosystem services based on soil microbial parameters.
AB  - Phytostabilization is a promising option for the remediation of metal
      contaminated soils which requires the implementation of long-term monitoring
      programs. We here propose to incorporate the paradigm of "adaptive monitoring",
      which enables monitoring programs to evolve iteratively as new information
      emerges and research questions change, to metal phytostabilization. Posing good
      questions that cover the chemical, toxicological and ecological concerns
      associated to metal contaminated soils is critical for an efficient long-term
      phytostabilization monitoring program. Regarding the ecological concerns, soil
      microbial parameters are most valuable indicators of the effectiveness of metal
      phytostabilization processes in terms of recovery of soil health. We suggest to
      group soil microbial parameters in higher-level categories such as "ecological
      attributes" (vigor, organization, stability) or "ecosystem services" in order to
      facilitate interpretation and, most importantly, to provide long-term
      phytostabilization monitoring programs with the required stability through time
      against changes in techniques, methods, interests, etc. that will inevitably
      occur during the monitoring program. Finally, a Phytostabilization Monitoring
      Card, based on both ecological attributes and ecosystem services, for soil
      microbial properties is provided.

PMID- 24933898
TI  - Arundo donax L., a candidate for phytomanaging water and soils contaminated by
      trace elements and producing plant-based feedstock. A review.
AB  - Plants and associated microorganisms are used to remediate anthropogenic
      metal(loid) contamination of water, soils and sediments. This review focuses on
      the potential of Arundo donax L. (Giant reed) for alleviating risks due to soils,
      water, and sediments contaminated by trace elements (TE), with emphasis on its
      advantages and limits over macrophytes and perennial grasses used for bioenergy
      and plant-based feedstock. Arundo donax is relevant to phytomanage TE
      contaminated matrices, notably in its native area, as it possesses
      characteristics of large biomass production even under nutrient and abiotic
      stresses, fast growth rate, TE tolerance and accumulation mainly in below ground
      plant parts. Cultivating A. donax on contaminated lands and in constructed
      wetlands can contribute to increase land availability and limit the food vs.
      plant-based feedstock controversy. To gain more tools for decision-taking and
      sustainable management,further researches on A. donax should focus on:
      interactions between roots, TE exposure, and rhizosphere and endophytic
      microorganisms; biomass response to (a)biotic factors; sustainable agricultural
      practices on marginal and contaminated land; integration into local, efficient,
      energy and biomass conversion chains with concern to biomass quality and
      production; Life-Cycle Assessment including contaminant behavior, as well as
      environmental, agricultural and socio-economic benefits and drawbacks.

PMID- 24933899
TI  - Effects of soil type and genotype on cadmium accumulation by rootstalk crops:
      implications for phytomanagement.
AB  - The variations of Cd accumulation in three rootstalk crop species (radish, carrot
      and potato) were investigated by using twelve cultivars grown in acidic
      Ferralsols and neutral Cambisols under two Cd treatments (0.3 and 0.6 mg kg(-1))
      in a pot experiment The result showed that the total Cd uptake was significantly
      affected by genotype, soil type and interaction between them, suggesting the
      importance of selecting proper cultivars for phytoextraction in a given soil
      type. Among the cultivars tested, potato cultivar Luyin No.1 in Ferralsols and
      radish cultivar Zhedachang in Cambisols exhibited the highest Cd phytoextraction
      efficiency in aerial parts (4.45% and 0.59%, respectively) under 0.6 mg kg-1 Cd
      treatment. Furthermore, the Cd concentrations in their edible parts were below
      the National Food Hygiene Standard of China (0.1 mg kg(-1), fresh weight).
      Therefore, phytomanagement of slightly Cd-contaminated soils using rootstalk
      crops for safe food production combined with long-term phytoextraction was
      feasible, and potato cultivar Luyin No.1 for Ferralsols and radish cultivar
      Zhedachang for Cambisols were promising candidates for this approach.

PMID- 24933900
TI  - Effects of copper sulfate on seedlings of Prosopis pubescens (screwbean
      mesquite).
AB  - Phytoextraction is an established method of removal of heavy metals from
      contaminated soils worldwide. Phytoextraction is most efficient if local plants
      are used in the contaminated site. We propose that Prosopis pubescens (Screw bean
      mesquite) would be a successful phytoextractor of copper in our local soils. In
      order to determine the feasibility of using Screw bean mesquite, we utilized
      inductively-coupled plasma-optical emission spectroscopy (ICP-OES) and elemental
      analysis to observe the uptake of copper and the effects on macro and micro
      nutrients within laboratory-grown seedlings. We have previously shown that P.
      pubescens is a hyperaccumulator of copper in soil-grown seedlings. Light and
      transmission electron microscopy demonstrated death of root cells and
      ultrastructural changes due to the presence of copper from 50 mg/L - 600 mg/L.
      Ultrastructural changes included plasmolysis, starch accumulation, increased
      vacuolation and swollen chloroplasts with disarranged thylakoid membranes in
      cotyledons. Inductively coupled plasma-optical emission spectroscopy analyses of
      macro- and micro-nutrients revealed that the presence of copper sulfate in the
      growth medium of Petri-dish grown Prosopis pubescens seedlings resulted in
      dramatic decreases of magnesium, potassium and phosphorus. At 500-600 mg/L of
      copper sulfate, a substantial increase of sulfur was present in roots.

PMID- 24933901
TI  - Effects of high nutrient supply on the growth of seven bamboo species.
AB  - Over the last decade, bamboo has emerged as an interesting plant for the
      treatment of various polluted waters using plant-based wastewater treatment
      systems. In these systems, nitrogen and phosphorous concentrations in wastewater
      can exceed plant requirements and potentially limit plant growth. The effects of
      two nutrient rates on the growth of seven bamboo species were assessed in a one
      year experiment: Dendrocalamus strictus, Thyrsostachys siamensis, Bambusa
      tuldoides, Gigantochloa wrayi, Bambusa oldhamii, Bambusa multiplex and Bambusa
      vulgaris. Nutrient rates were applied with a 20:20:20 NPK fertilizer as 2.6 and
      13.2 t.ha.yr(-1) NPK to three-year-old bamboo planted in 70 L containers.
      Morphological characters, photosynthetic responses, and NPK content in bamboo
      tissues were investigated. Under high-nutrient supply rate, the main trend
      observed was an increase of culm production but the culms' diameters were
      reduced. For the seven species, the above ground biomass yield tended to increase
      with high-nutrient rate. Increasing in nutrient rates also improved the
      photosynthetic activity which is consistent with the increase of nitrogen and
      phosphorus contents measured in plant tissues. All the bamboo species tested
      appears suitable for wastewater treatment purposes, but the species Bambusa
      oldhamii and Gigantochloa wrayi showed the higher biomass yield and nutrient
      removaL

PMID- 24933902
TI  - Selection and combustion of Ni-hyperaccumulators for the phytomining process.
AB  - Ni recovery from serpentine soils by phytomining has proved feasible. Phytomining
      involves the crop of hyperaccumulating plants with high Ni contents and the
      valorization of Ni by pyro or hydrometallurgical process. In order to evaluate
      the Ni content of different plants, we analyzed the organs of 14
      hyperaccumulators from three genera: Alyssum, Leptoplax and Bornmuellera. The
      highest concentration was recorded in the leaves of Leptoplax (34.3 +/- 0.7 mg g(
      1)DM). Additionally, we investigated biomass combustion which is the first step
      of the process we designed to obtain a nickel salt. We showed that temperature
      and duration were important parameters to ensure a good quality of ashes. At the
      bench scale, the best conditions were 550 degrees C and 3 h. In this way, we
      obtained ashes in which Ni could reach 20 wt%. Biomass ashes can be considered as
      a bio-ore for recovering metal value.

PMID- 24933903
TI  - Cr localization and speciation in roots of chromate fed Helianthus annuus L.
      seedlings using synchrotron techniques.
AB  - In order to gain knowledge on the potential use of Helianthus annuus L. for the
      remediation of Cr(VI) polluted waters, hydroponics experiments were set up to
      determine Cr uptake and tolerance in different Cr(VI)-sulfate conditions, and Cr
      biotransformations. Results indicated that Cr(VI) promoted seed germination, and
      plant tolerance was higher at younger plant stages. Cr uptake was dependent on
      sulfate concentrations. The highest Cr levels in roots and shoots (13,700 and
      2,500 mg kg(-1) dry weight (DW), respectively) were obtained in 1 mM sulfate. The
      lowest Cr uptake in roots (10,600 mg kg(-1) DW) was observed in seedlings treated
      with no sulfate. In shoots, Cr concentration was of 1,500 mg kg(-1)DW for the 1
      mM sulfate treatment, indicating a different level of interaction between
      chromate and sulfate in both tissues. For the first time, using micro X-ray
      florescence (muXRF), we demonstrated Cr reaches the root stele and is located in
      the walls of xylem vessels. Bulk and micro X-ray Absorption Near-Edge Structure
      (muXANES) results showed that Cr in the roots is mostly in the form of Cr(III)
      phosphate (80%), with the remainder complexed to organic acids. Our results
      suggest this plant species may serve for Cr(VI) rhizofiltration purposes.

PMID- 24933904
TI  - Metal uptake by native plants and revegetation potential of mining sulfide-rich
      waste-dumps.
AB  - Waste dumps resulting from metal exploitation create serious environmental
      damage, providing soil and water degradation over long distances.
      Phytostabilization can be used to remediate these mining sites. The present study
      aims to evaluate the behavior of selected plant species (Erica arborea, Ulex
      europaeus, Agrostis delicatula, and Cytisus multiflorus) that grow spontaneously
      in three sulfide-rich waste-dumps (Lapa Grande, Cerdeirinha, and Penedono,
      Portugal). These sites represent different geological, climatic and floristic
      settings. The results indicate distinctive levels and types of metal
      contamination: Penedono presents highest sulfate and metal contents, especially
      As, with low levels of Fe. In contrast, at Lapa Grande and Cerdeirinha Fe, Mn,
      and Zn are the dominant metals. In accordance, each waste dump develops a typical
      plant community, providing a specific vegetation inventory. At Penedono, Agrostis
      delicatula accumulates As, Pb, Cu, Mn, and Zn, showing higher bioaccumulation
      factors (BF) for Mn (32.1) and As (24.4). At Cerdeirinha, Ulex europaeus has the
      highest BF for Pb (984), while at Lapa Grande, Erica arborea presents high BF for
      Mn (9.8) and Pb (8.1). Regarding TF, low values were obtained for most of the
      metals, especially As (TF < 1). Therefore, the results obtained from
      representative plant species suggest appropriate behavior for phytostabilization
      measures.

PMID- 24933905
TI  - Cadmium dynamics in the rhizosphere and Cd uptake of different plant species
      evaluated by a mechanistic model.
AB  - Maize, sunflower,flax, and spinach differed in the accumulation of Cd when grown
      on a Cd contaminated soil. This was mainly due to the different Cd net influx,
      In, that varied among species by a factor of up to 30. The objective of this
      study was to find possible reasons for the different Cd In by using a mechanistic
      model. After 14 days of Cd uptake the model calculated only a small Cd depletion
      at the root surface, e.g. from 0.22 mumol L(-1) down to 0.19 mumol L(-1) for
      maize and from 0.48 mumol L(-1) down to 0.35 mumol L(-1)for spinach. Even so the
      model always overestimated the Cd I(n), for spinach by a factor of 1.5 and for
      maize by a factor of 10. Only simulating a decrease of C(Li) or the root
      absorbing power, alpha, by 40% to 90% gave an agreement of calculated and
      measured I(n),. This may be interpreted as that about 40% in the case of spinach
      and 90% in the case of maize of the Cd in soil solution were not accessible for
      plant uptake. The high sensitivity to alpha also shows that not the Cd transport
      to the root but alpha was limiting the step for Cd uptake.

PMID- 24933906
TI  - Cadmium removal by Lemna minor and Spirodela polyrhiza.
AB  - The present study investigates the ability of two genus of duckweed (Lemna minor
      and Spirodela polyrhiza) to phytoremediate cadmium from aqueous solution.
      Duckweed was exposed to six different cadmium concentrations, such as,
      0.5,1.0,1.5, 2.0, 2.5, and 3.0 mg/L and the experiment was continued for 22 days.
      Water samples were collected periodically for estimation of residual cadmium
      content in aqueous solution. At the end of treatment period plant samples were
      collected and accumulated cadmium content was measured. Cadmium toxicity was
      observed through relative growth factor and changes in chlorophyll content
      Experimental results showed that Lemna minor and Spirodela polyrhiza were capable
      of removing 42-78% and 52-75% cadmium from media depending upon initial cadmium
      concentrations. Cadmium was removed following pseudo second order kinetic model
      Maximum cadmium accumulation in Lemna minor was 4734.56 mg/kg at 2 mg/L initial
      cadmium concentration and 7711.00 mg/kg in Spirodela polyrhiza at 3 mg/L initial
      cadmium concentration at the end of treatment period. Conversely in both cases
      maximum bioconcentration factor obtained at lowest initial cadmium
      concentrations, i.e., 0.5 mg/L, were 3295.61 and 4752.00 for Lemna minor and
      Spirodela polyrhiza respectively. The present study revealed that both Lemna
      minor and Spirodela polyrhiza was potential cadmium accumulator.

PMID- 24933907
TI  - Plant growth-promoting bacteria facilitate the growth of barley and oats in salt
      impacted soil: implications for phytoremediation of saline soils.
AB  - Plant growth-promoting bacteria (PGPB) strains that contain the enzyme 1-amino
      cyclopropane-1-carboxylate (ACC) deaminase can lower stress ethylene levels and
      improve plant growth. In this study, ACC deaminase-producing bacteria were
      isolated from a ) salt-impacted ( 50 dS/m) farm field, and their ability to
      promote plant growth of barley 1): and oats in saline soil was investigated in
      pouch assays (1% NaCI), greenhouse trials (9.4 dS/m), and field trials (6-24
      dS/m). A mix of previously isolated PGPB strains UW3 (Pseudomonas sp.) and UW4
      (P. sp.) was also tested for comparison. Rhizobacterial isolate CMH3 (P.
      corrugata) and UW3+UW4 partially alleviated plant salt stress in growth pouch
      assays. In greenhouse trials, CMH3 enhanced root biomass of barley and oats by
      200% and 50%, respectively. UW3+UW4, CMH3 and isolate CMH2 also enhanced barley
      and oat shoot growth by 100%-150%. In field tests, shoot biomass of oats tripled
      when treated with UW3+UW4 and doubled with CHM3 compared with that of untreated
      plants. PGPB treatment did not affect salt uptake on a per mass basis; higher
      plant biomass led to greater salt uptake, resulting in decreased soil salinity.
      This study demonstrates a method for improving plant growth in marginal saline
      soils. Associated implications for salt

PMID- 24933908
TI  - Physiological and proteomic responses of different willow clones (Salix fragilis
      x alba) exposed to dredged sediment contaminated by heavy metals.
AB  - High biomass producing species are considered as tools for remediation of
      contaminated soils. Willows (Salix spp.) are prominent study subjects in this
      regard. In this study, different willow clones (Salix fragilis x alba) were
      planted on heavy-metal polluted dredging sludge. A first objective was assessment
      of the biomass production for these clones. Using a Gupta statistic, four clones
      were identified as high biomass producers (HBP). For comparison, a group of four
      clones with lowest biomass production were selected (LBP). A second objective was
      to compare metal uptake as well as the physiological and proteomic responses of
      these two groups. All these complementary data's allow us to have a better
      picture of the health of the clones that would be used in phytoremediation
      programs. Cd, Zn, and Ni total uptake was higher in the HBPs but Pb total uptake
      was higher in LBPs. Our proteomic and physiological results showed that the LBPs
      were able to maintain cellular activity as much as the HBPs although the
      oxidative stress response was more pronounced in the LBPs. This could be due to
      the high Pb content found in this group although a combined effect of the other
      metals cannot be excluded.

PMID- 24933909
TI  - Study of the spatial distribution of mercury in roots of vetiver grass
      (Chrysopogon zizanioides) by micro-pixe spectrometry.
AB  - Localization of Hg in root tissues of vetivergrass (Chrysopogon zizanioides) was
      investigated by micro-Proton Induced X-ray Emission (PIXE) spectrometry to gain a
      better understanding of Hg uptake and its translocation to the aerial plant
      parts. Tillers of C. zizanioides were grown in a hydroponic culture for 3 weeks
      under controlled conditions and then exposed to Hg for 10 days with or without
      the addition of the chelators (NH(4))(2)S(2)O(3) or KI. These treatments were
      used to study the effects of these chelators on localization of Hg in the root
      tissues to allow better understanding of Hg uptake during its assisted
      phytoextraction. Qualitative elemental micro-PIXE analysis revealed that Hg was
      mainly localized in the root epidermis and exodermis, tissues containing suberin
      in all Hg treatments. Hg at trace levels was localized in the vascular bundle
      when plants were treated with a mercury solution only. However, higher Hg
      concentrations were found when the solution also contained (NH(4))(2)S(2)O(3) or
      KI. This finding is consistent with the observed increase in Hg translocation to
      the aerial parts of the plants in the case of chemically induced Hg
      phytoextraction.

PMID- 24933910
TI  - Phytoremediation potential of Phragmites australis in Hokersar wetland - a Ramsar
      site of Kashmir Himalaya.
AB  - Heavy metals are an important class of pollutants with both lethal and sublethal
      effects on organisms. Wetlands are cheap natural alternatives for removal of
      heavy metals from soils; however, wetland plants vary greatly in their degree of
      metal uptake. Hokersar wetland, a Ramsar site of Kashmir Himalaya, India is a
      game reserve of international importance that provides suitable habitat for
      resident birds and an excellent stopover point for migratory birds visiting from
      Palaearctic breeding grounds in Central Asia, China, N-Europe and Siberia. The
      toxicity of chronic dietary metal exposure in birds may have adverse reproductive
      effects which include decreased egg production, decreased hatchability, and
      increased hatchling mortality. Thus, the present study aimed to assess the heavy
      metal sequestration capability of one of the most common wetland plant species
      Phragmites australis in Hokersar wetland. The accumulation of the different
      elements was in order of Al > Mn > Ba > Zn > Cu > Pb > Mo > Co > Cr > Cd > Ni.
      Translocation factor, i.e. ratio of shoot to root metal concentration revealed
      that metals were largely retained in the roots of P. australis, thus reducing the
      supply of metals to avifauna and preventing their bio-accumulation.

PMID- 24933911
TI  - Single and combined effects of exposure concentration and duration on biological
      responses of Ceratophyllum demersum L. exposed to Cr species.
AB  - This study aimed to demonstrate the ways in which two chromium species, Cr (III)
      and Cr (VI), can affect various physiological and biochemical parameters in the
      plant Ceratophyllum demersum L., and to evaluate the single and combined impact
      of exposure concentration and duration. C. demersum was exposed to Cr (III) and
      Cr (VI) at a variety of concentrations (1, 2, 5, and 10 mM) and for differing
      durations (1, 2, 4, and 7 days), after which Cr accumulation, relative growth
      rate (RGR), malondialdehyde (MDA) content, electrical conductivity (EC),
      photosynthetic pigmentation, proline content and antioxidant enzyme activities
      were examined. The single and combined effects of exposure duration and Cr
      concentration on each parameter were determined using a two-way analysis of
      variance. For both the Cr (III) and Cr (VI) applications, it was observed that
      concentration had a significant effect on all parameters assessed. However,
      duration had no statistically significant effect on proline content in the Cr
      (III) application, or on MDA and protein content in the Cr (VI) application. It
      was determined that concentration exerted greater effects than duration for both
      Cr species studied. In addition, the results indicated that duration and
      concentration had a synergistic effect on variations of RGR, EC, protein content,
      and antioxidant enzyme activities in both the Cr (III) and Cr (VI) applications.
      These results may be useful when planning further phytoremediation and plant
      biotechnology studies.

PMID- 24933912
TI  - Potential of Spartina maritima in restored salt marshes for phytoremediation of
      metals in a highly polluted estuary.
AB  - Sedimentary abiotic environment, and concentration and stock of nine metals were
      analyzed in vegetation and sediments to evaluate the phytoremediation capacity of
      restored Spartina maritima prairies in the highly polluted Odiel Marshes (SW
      Iberian Peninsula). Samples were collected in two 10 -m long rows parallel to the
      tidal line at two sediments depths (0-2 cm and 2-20 cm). Metal concentrations
      were measured by inductively coupled plasma spectroscopy. Iron, aluminum, copper,
      and zinc were the most concentrated metals. Every metal, except nickel, showed
      higher concentration in the root zone than at the sediment surface, with values
      as high as ca. 70 g Fe kg(-1). The highest metal concentrations in S. maritima
      tissues were recorded in its roots (maximum for iron in Spartina roots: 4160.2 +/
      945.3 mg kg(-1)). Concentrations of aluminum and iron in leaves and roots were
      higher than in superficial sediments. Rhizosediments showed higher concentrations
      of every metal than plant tissues, except for nickel. Sediment metal stock in the
      first 20 cm deep was ca. 170.89 t ha(-1). Restored S. maritima prairies, with
      relative cover of 62 +/- 6%, accumulated ca. 22 kg metals ha(-1). Our results
      show S. maritima to be an useful biotool for phytoremediation projects in
      European salt marshes.

PMID- 24933913
TI  - Arsenic uptake by Lemna minor in hydroponic system.
AB  - Arsenic is hazardous and causes several ill effects on human beings.
      Phytoremediation is the use of aquatic plants for the removal of toxic pollutants
      from external media. In the present research work, the removal efficiency as well
      as the arsenic uptake capacity of duckweed Lemna minor has been studied. Arsenic
      concentration in water samples and plant biomass were determined by AAS. The
      relative growth factor of Lemna minor was determined. The duckweed had potential
      to remove as well as uptake arsenic from the aqueous medium. Maximum removal of
      more than 70% arsenic was achieved atinitial concentration of 0.5 mg/1 arsenic on
      15th day of experimental period of 22 days. Removal percentage was found to
      decrease with the increase in initial concentration. From BCF value, Lemna minor
      was found to be a hyperaccumulator of arsenic at initial concentration of 0.5
      mg/L, such that accumulation decreased with increase in initial arsenic
      concentration.

PMID- 24933914
TI  - Bioremediation of an iron-rich mine effluent by Lemna minor.
AB  - Contamination of water resources by mine effluents is a serious environmental
      problem. In a old coal mine, in the north of Portugal (Sao Pedro da Cova,
      Gondoma),forty years after the activity has ended, a neutral mine drainage, rich
      in iron (FE) it stills being produced and it is continuously released in local
      streams (Ribeiro de Murta e Rio Ferreira) and in surrounding lands. The species
      Lemna minor has been shown to be a good model for ecotoxicological studies and it
      also has the capacity to bioaccumulate metals. The work aimed test the potential
      of the species L. minor to remediate this mine effluent, through the
      bioaccumulation of Fe, under greenhouse experiments and, at the same time,
      evaluate the time required to the maximum removal of Fe. The results have shown
      that L. minor was able to grow and develop in the Fe-rich effluent and
      bioaccumulating this element. Throughout the 21 days of testing it was found that
      there was a meaningful increase in the biomass of L. minor both in the
      contaminated and in the non-contaminated waters. It was also found that
      bioaccumulation of Fe (iron) occurred mainly during the first 7 days of testing.
      It was found that L. minor has potential for the bioremediation of effluents rich
      in iron.

PMID- 24933915
TI  - Phytoremediation efficiency of a pcp-contaminated soil using four plant species
      as mono- and mixed cultures.
AB  - Bioremediation of soil polluted by pentachlorophenol (PCP) is of great importance
      due to the persistence and carcinogenic properties of PCP. Phytoremediation has
      long been recognized as a promising approach for removal of PCP from soil. The
      present study was conducted to investigate the capability of four plant species;
      white clover, ryegrass, alfalfa, and rapeseed grown alone and in combination to
      remediate pentachlorophenol contaminated soil. After 60 days cultivation, white
      clover, raygrass, alfalfa, and rapeseed all significantly enhanced the
      degradation of PCP in soils. Alfalfa showed highest efficiency for the removal of
      PCP in single cropping flowed by rapeseed and ryegrass. Mixed cropping
      significantly enhanced the remediation efficiencies as compared to single
      cropping; about 89.84% of PCP was removed by mixed cropping of rapeseed and
      alfalfa, and 72.01% of PCP by mixed cropping of rape and white clover. Mixed
      cropping of rapeseed with alfalfa was however far better for the remediation of
      soil PCP than single cropping. An evaluation of soil biological activities as a
      monitoring mechanism for the bioremediation process of a PCP-contaminated soil
      was made using measurements of microbial counts and dehydrogenase activity.

PMID- 24933916
TI  - Cadmium tolerance and accumulation of Elsholtzia argyi origining from a zinc/lead
      mining site - a hydroponics experiment.
AB  - In this study, a hydroponics experiment was conducted to investigate the
      characteristics of Cd tolerance and accumulation of Elsholtzia argyi natively
      growing on the soil with high levels of heavy metals in a Zn/Pb mining site.
      Seedlings of E. argyi grown for 4 weeks and then were treated with 0(CK),
      5,10,15, 20, 25, 30, 40, 50,100 umM Cd for 21 days. Each treatment had three
      replications. No visual toxic symptoms on shoots of E. argyi were observed at Cd
      level < or = 50 muM. The results indicated that the dry biomass of each tissue
      and the whole plants of the treatments with < or =40 umM cadmium were similar to
      that of the control, implying that E. argyi was a cadmium tolerant plant. The
      results also showed that the shoot Cd concentration significantly (P < 0.05)
      increased with the increase in the Cd level in nutrient solution. The shoot Cd
      concentration of the treatment with 40 umM Cd was as high as 237.9 mg kg(-1),
      which was higher than 100 mg kg(-1), normally used as the threshold concentration
      for identifying the Cd hyperaccumulating plant. It could be concluded that E.
      argyi was a Cd tolerant and accumulating plant species.

PMID- 24933917
TI  - Combined use of alkane-degrading and plant growth-promoting bacteria enhanced
      phytoremediation of diesel contaminated soil.
AB  - Inoculation of plants with pollutant-degrading and plant growth-promoting
      microorganisms is a simple strategy to enhance phytoremediation activity. The
      objective of this study was to determine the effect of inoculation of different
      bacterial strains, possessing alkane-degradation and 1-amino-cyclopropane-1 
      carboxylic acid (ACC) deaminase activity, on plant growth and phytoremediation
      activity. Carpet grass (Axonopus affinis) was planted in soil spiked with diesel
      (1% w/w) for 90 days and inoculated with different bacterial strains, Pseudomonas
      sp. ITRH25, Pantoea sp. BTRH79 and Burkholderia sp. PsJN, individually and in
      combination. Generally, bacterial application increased total numbers of
      culturable hydrocarbon-degrading bacteria in the rhizosphere ofcarpet grass,
      plant biomass production, hydrocarbon degradation and reduced genotoxicity.
      Bacterial strains possessing different beneficial traits affect plant growth and
      phytoremediation activity in different ways. Maximum bacterial population, plant
      biomass production and hydrocarbon degradation were achieved when carpet grass
      was inoculated with a consortium of three strains. Enhanced plant biomass
      production and hydrocarbon degradation were associated with increased numbers of
      culturable hydrocarbon-degrading bacteria in the rhizosphere of carpet grass. The
      present study revealed that the combined use of different bacterial strains,
      exhibiting different beneficial traits, is a highly effective strategy to improve
      plant growth and phytoremediation activity.

PMID- 24933918
TI  - Safe patient care legislation.

PMID- 24933919
TI  - Michigan and the nation need a raise: the case for a higher minimum wage.

PMID- 24933921
TI  - Why should RNs care about raising the minimum wage?

PMID- 24933920
TI  - MNA RNs say: 'Robin Hood Tax' on Wall Street can heal Detroit.

PMID- 24933922
TI  - Raising the alarm: patient care at risk from too many... bells, beeps & buzzers
      independent study.

PMID- 24933923
TI  - Member profile: Heather Freeman, RN.

PMID- 24933924
TI  - Progress on prevention and cure.

PMID- 24933925
TI  - Building an immune toolbox.

PMID- 24933927
TI  - New anti-homosexuality laws raise international concerns.

PMID- 24933926
TI  - Obituary: Reinhard Kurth.

PMID- 24933928
TI  - ADA fellow in leadership award.

PMID- 24933929
TI  - Dennett's echo.

PMID- 24933930
TI  - Words beyond death: literary form and its intentions in Paul Zweig's last works.

PMID- 24933931
TI  - Healing, harming and Hippocrates: physician-assisted suicide in Roman medicine.

PMID- 24933932
TI  - Care and progress are the spirit of the NHS.

PMID- 24933933
TI  - The future of GP premisises is on shaky ground.

PMID- 24933934
TI  - Older people's care is not a burden.

PMID- 24933935
TI  - Education: give medical and dental training more teeth.

PMID- 24933936
TI  - Technology: moving pictures.

PMID- 24933937
TI  - Mental health: a closer look at the mental health evolution.

PMID- 24933938
TI  - Workforce: pedal to the metal to improve the NHS.

PMID- 24933939
TI  - Staff engagement: revolutionise healthcare reform.

PMID- 24933940
TI  - Leadership: the challenge for CCGs a year on.

PMID- 24933941
TI  - [An alternative pathway of colorectal cancer development. Endoscopic and
      morphological features of serrated lesions. Review].

PMID- 24933942
TI  - [Fecal calprotectin as a biomarker effectiveness of various interventions in
      patients with inflammatory bowel disease].
AB  - Among the chronic diseases of the gastrointestinal tract of the special place
      occupied by inflammatory bowel disease (IBD), in which the lining of the
      intestine produces a significant number of neutrophils, which has prompted
      researchers and clinicians use a protein derived from neutrophils as a biomarker
      for the assessment of the intestinal wall and the effectiveness of treatment in
      patients IBD. One of these proteins is calprotectin (CP), which can be considered
      as a biomarker of activation, destruction and loss of neutrophil cells, to a
      lesser extent-- the activated monocytes and macrophages. Various studies have
      shown that the concentration of fecal calprotectin (FCP) correlates well with
      endoscopic and histological parameters of intestinal inflammation. Test the FCP
      can be used in healthy first-degree relatives of patients with IBD to assess the
      possible presence of subclinical variant of intestinal inflammation in this
      population. Thus, a simple test of the FCP can reduce the needs of various
      expensive and invasive method, including costs associated with them, especially
      in younger patients, where in terms of differential diagnosis of IBD is often not
      included neoplasia of the intestine. FCP is a non-invasive, inexpensive and at
      the same time, highly sensitive and specific biomarker that can be used
      successfully in the diagnosis, evaluation of the efficacy of treatment and
      predicting recurrence.

PMID- 24933943
TI  - [Prognostic factors of ulcer colitis flow].
AB  - The aim of the study was to optimize curation of patients with ulcer colitis
      based on study of prognostic factors of disease flow. MATERIALS AND METHODS: The
      influence of clinical and instrumental data on the severity of the disease was
      evaluated in 101 patients with ulcerative colitis (UC) within first 5 years from
      the disease onset. Blood molecular genetic testing was performed to study the
      gene polymorphism of IL-12 b A1188C, IL-17 A G-197A, IL-17, F T7488C, TNF-alpha 
      308 G-308A on the phenotype of the disease. RESULTS: The effect of IL-17 F
      T7488C, TNF-alpha G-308A gene polymorphisms at the risk of the formation of
      inflammatory polyps, the prevalence of lesions of the pathological process in the
      colonic mucosa in the first 5 years disease flow from moderate to severe
      ulcerative colitis established the prognostic factors of systemic
      immunosuppressive therapy. However the Influence of IL-12 b A1188C, IL-17 A G
      197A gene polymorphisms on the phenotype have been no identified. CONCLUSIONS:
      The contribution of the studied IL-17 F T7488C, TNF-alpha G-308A gene
      polymorphisms is highly related to the disease phenotype manifestations and
      peculiar issues associated with therapy volume. Identified prognostic risk
      factors of systemic immunosuppressant needs allowed us to develop an algorithm of
      supervision of patients with ulcerative colitis.

PMID- 24933944
TI  - [The changes in serum concentrations of interleukin-17 in diseases gastroduodenal
      zone].
AB  - THE PURPOSE OF THE STUDY: Identify on patients with chronic gastritis, peptic
      ulcer disease, gastric cancer, serum concentrations of interleukin-17 and its
      relationship to clinical and morphological and serological characteristics.
      MATERIAL AND METHODS: A comprehensive survey of 156 patients with diseases
      gastroduodenal zone. Diagnostic emphasis was placed on ELISA method as defined in
      the serum of IL-17, pepsinogen-I, - II, total antibodies to CagA Helicobacter
      pylori. RESULTS: In studied patients revealed changes in the concentration of
      interleukin-17 correlate with the stage of atrophy of the gastric mucosa, tumor,
      level of pepsinogen, antibodies to the Helicobacter pylori. CONCLUSION: The data
      obtained allow to recommend the use of interleukin-17 in serological differential
      diagnosis of diseases gastroduodenal zone.

PMID- 24933945
TI  - [The character of the morphological changes of the mucous membrane of the large
      intestine and the genetic polymorphism of IL-1RA, IL-1B, IL-4 TNFA in patient
      with irritable bowel syndrome].
AB  - The aim of this study was to evaluate the presence or absence of a relationship
      between the variants of the course of IBS and their association with genetic
      polymorphisms of genes and intergenic interaction of cytokines. MATERIALS AND
      METHODS: The sample consisted of 81 patients, the diagnosis was verified
      according to the criteria of the Rome III, were isolated psychopathological,
      morphological complications, extra-intestinal symptoms. Polymorphism genotyping
      IL-1Ra, IL-b, IL-4, TNFa performed by PCR. Statistical treatment are a non
      parametric analysis of multiple comparisons, hierarchical log-linear analysis. It
      is found out the relation between the clinical variants with morphological
      changes of the mucous membrane of the large intestine, the association between
      gender characteristics of patients with IBS is established and with genetic
      polymorphisms of cytokines.

PMID- 24933946
TI  - [Influence of the comorbidity diseases and risk factors on development of the
      combined peptic ulcer of the stomach and the duodenum].
AB  - RESEARCH OBJECTIVE: To define influence of the comorbidity diseases and risk
      factors of development of the combined peptic ulcer of a stomach and duodenum.
      MATERIALS AND METHODS: As a result of carried-out poll and inspection 250
      patients with an exacerbation of a peptic ulcer were surveyed. Patients were
      distributed in 3 groups of observation depending on localization of ulcerative
      process. At all surveyed questioning was carried out, data on hereditary load,
      smoking, alcohol intake, existence of somatopathies were specified, clinic
      morphological implications of a peptic ulcer were studied. RESULTS: The peptic
      ulcer of a stomach is characteristic for women (72.1%) and develops mainly aged
      from 45 till 59 years (60.3%). Peptic ulcer of duodenum men (76.3%) suffer
      mainly, the debut is the share in most cases of age from 18 to 44 years (79.1%).
      The combined canker of a stomach and duodenum meets at males (61.2%) more often,
      is initially involved in process ulcerogenesis by duodenum generally aged from 30
      till 44 years (64.2%), accession of a canker of a stomach happens is delayed (at
      38.8% within 16 and more years). In the analysis of risk factors at patients with
      the combined peptic ulcer of a stomach and duodenum depending on existence or
      absence specific to this category of patients of a background from such
      comorbidity diseases as IBS, HOBL and widespread osteochondrosis taped that
      larger prevalence of smoking (100%) and as the use (50%) and the excessive use
      (50%), alcohol are characteristic for the patients having a high comorbidity (a
      combination of three above nosologies). CONCLUSION: The greatest interest in
      respect of possible communication with formation of the combined peptic ulcer of
      a stomach and duodenum is represented by IBS, HOBL and osteochondrosis. And major
      factors of risk were smoking, the excessive alcohol intake, the burdened
      heredity.

PMID- 24933947
TI  - [Psychological respond to the disease and treatment devotion].
AB  - THE PURPOSE OF THE STUDY: To evaluate the degree of adherence to treatment in
      comparison with the psychological reactions to the disease in patients with
      chronic diseases of the digestive system. MATERIAL AND METHODS: We examined 106
      patients with chronic diseases of the upper gastrointestinal tract. Psychological
      reactions to the disease were studied using personality questionnaires of the
      Bekhterev Institute (the St. Petersburg V.M. Bekhterev Psychoneurological
      Research Institute), adherence to treatment--using a specially designed
      questionnaire. 52 patients were polled again at 6 months after discharge from
      hospital. RESULTS: High adherence was diagnosed in 47.2%, satisfactory--in 44.3%,
      and lower--in 8.5% of cases. Hypernosognosia reaction to the disease in patients
      with low levels of compliance were more frequent than in patients with a high
      level of compliance (77.8 and 12.0%, respectively). The obtained result suggests
      that excessive emotional tension, high levels of anxiety and the stress response
      prevent adequate inclusion of patients in the treatment process. A similar
      situation persists in 6 months after discharge from hospital. This is confirmed
      by clinical observations indicating that this type of reaction to a disease
      peculiar to the mature person who knows how to extract the experience of adverse
      life situations. CONCLUSIONS: The results confirm the absence of an adequate
      level of adherence to treatment in patients with chronic diseases of the
      digestive system. In particular this applies to patients with inadequate
      emotional response to diseases. In this regard, in terms of improving adherence
      increases the importance of timely diagnosis of anxiety and depression with
      subsequent correction of the violations.

PMID- 24933948
TI  - [Diagnostic value of autoantibodies to asialoglycoprotein receptor in autoimmune
      hepatitis].
AB  - Among 106 patients with autoimmune liver disease in 12 (11.3%) were found
      autoantibodies to asialoglycoprotein receptor (anti-ASGPR): in 5 (9.1%) of 55
      with PBC, and 4 (17.4%) of 23 with AIH and 3 (10.7%) of 28 patients with syndrome
      chiasm (PBC + AIH). Detection of antibodies against the ASGPR is an effective
      method for diagnosis of autoimmune hepatitis. Further improvement of this method
      allows for monitoring and disease. Anti-ASGPR levels correlate with biochemical
      parameters and with the severity and manifestation autoimmune processes in
      patients with autoimmune hepatitis.

PMID- 24933949
TI  - [Mutual influence of gastrointestinal pathology and hospital-acquired infection].
AB  - Review of the literature devoted to one of the most important problems of modern
      medicine--nosocomial infections (NI). In the article there are examined relevant,
      epidemiology, pathogenesis, and criteria for NO determining. Special attention is
      paid to the mutual influence of gastrointestinal tract pathology and nosocomial
      infections.

PMID- 24933950
TI  - [Nervous regulation of contractile function of the rectum].
AB  - Basic systems of autonomic regulation of contractile function of the rectum are
      presented. Activation of the parasympathetic system has a predominantly
      stimulatory influence on the contractile function of the rectum. Activation of
      alpha1-, alpha2- and beta2-adrenergic receptors of the sympathetic nervous system
      inhibits contractile function of the rectum, and activation of alphal-adrenergic
      receptors stimulates contractile function of rectum sphinkters. The data about
      the effect of serotoninergic, purinergic, peptidergic, and nitrergic systems on
      the contractile function of the rectum are also presented.

PMID- 24933951
TI  - [Non-surgical treatment of chronic anal fissure by intrasphincter injection of
      botulinum toxin type].

PMID- 24933952
TI  - [Effects of radiation of decimeter range on the motor function of the
      gastrointestinal and biliary tracts].
AB  - Characteristics of the motor function of the upper gastrointestinal tract, small
      intestine and colon and biliary tract under radiation of dm range were obtained.
      The radiation source was a mobile phone brand Nokya. Motor function of the
      gastrointestinal and biliary tract was evaluated recording electromyogram (EMG)
      from silver electrodes imposed on the body surface in the projection point of the
      corresponding abdominal organs; frequency (in minutes) and amplitude (mV) and EMG
      spikes are measured. The maximums of dm radiation induced stimulatory effect on
      motor function recorded at the esophagus, stomach, jejunum and descending part of
      the colon.

PMID- 24933953
TI  - [Thrombophilia as a cause of mesenterIc venous thrombosis in young patients].

PMID- 24933954
TI  - [Prevalence and risk factors of gastroduodenal and biliary system diseases in
      infants and preschool children].
AB  - To study the prevalence and risk factors of digestive diseases in children
      performed continuous screening questionnaire 786 children from 1.5 to 7 years.
      Were Revealed that 47.1 +/- 3.5% of children have symptoms of diseases of the
      gastrointestinal tract and biliary system. This symptoms occur in children aged 4
      to 7 years in 2.3 times more frequently than in children from 1.5 to 3 years. In
      depth study was revealed that the frequency of biliary dyskinesia (BD) was 33 +/-
      3.3%, chronic gastritis (CG) and gastroduodenitis (CGD)--6.2 +/- 1.8%, chronic
      cholecystitis--4.2 +/- 1.4%, functional disorders of the stomach (FSD)--2.8 +/-
      1.2%, and peptic duodenal ulcer (DU)--0.3 + 0.4%. In the structure of digestive
      diseases in children from 1.5 to 7 years on the 1st place are BD--70% on the 2nd-
      CG and CGD--14.7% on the 3rd chronic cholecystitis--8.9%, on the 4th FSD-5.9% and
      5th place DU-0.5%. For dispensary observation in the children's clinic with
      digestive diseases consist of only 7.9 +/- 1.9% of children, which is 5.9 times
      lower than according to the active diagnostics data. The leading medical and
      social risk factors and their complex influence on the formation of digestive
      disorders in infants and preschool children.

PMID- 24933955
TI  - [12th OESO World Congress--cancers of the esophagus from normal mucosa to tumor
      translating knowledge into cure].

PMID- 24933956
TI  - [Military everyday life of surgeon Kovanova].

PMID- 24933957
TI  - [Quantitative and qualitative evalution of polymorbidity in geriatric practice].

PMID- 24933958
TI  - [The study of hormonal status in children with gastroesophageal reflux disease].
AB  - The aim of this work is to study the level of some hormones and their role in the
      pathogenesis of gastroesophagal reflux disease (GERD) in children. MATERIALS AND
      METHODS: 40 children with GERD at the age 9 till 17 years of them 17 boys (42.5%)
      and 23 girls (57.5%) were examined. Content of somatostatin, gastrin, insulin,
      cortisol in the blood was studied by immunofermental method. Motor function of
      the sthomach was studied using the apparatus EGC-4M. RESULTS: The investigations
      which were performed revealed the fact that children with GERD have different
      concentration of somatostatin and gastrin depending on their age. In disturbances
      of interrelations of somatostatin and gastrin impairment of the stomach motility
      occurs. High level of insulin and cortisol is found in children with GERD. High
      level of insulin indicates of stimulation of protective and adaptative
      mechanisms. High level of cortisol intensifies catabolic processes, leads to
      disturbances of dynamic equilibration of aggressive-protective factors in the
      gastroduodenal zone. CONCLUSION: The results of our study revealed vital role of
      hormonal factors in the pathogenesis of GERD in children.

PMID- 24933959
TI  - [Biliary sludge: diagnosis and treatment at an outpatient's clinic].
AB  - The purpose of the study--to develop a diagnostic and management tactics for
      patients with biliary sludge (BS) in an outpatient setting. The study included
      115 patients who, according to the ultrasound revealed a BS. Own methodological
      approach used by ultrasound scan of the gall bladder and the interpretation of
      ultrasonographic BS types: Type 1 (suspension echo-positive particles) was set at
      59.1%, type 2 (low level of mobile like putty echo-positive bile)--23.5%, 3 type
      (like putty bile in the form of mobile and/or fixed clots)--17.4%. For the
      treatment of BS used drugs ursodeoxycholic acid. The daily dosage depends upon
      the type BS. For the treatment of type 1 requires a minimum of 1 month, 2 types-
      not less than 3 months. Sludge was the most resistant type 3, which is the
      duration of treatment was 6-12 months or more. Allocation of risk factors forming
      the BS is the basis for the formation of risk groups and prevention activities
      (including pharmacotherapeutic).

PMID- 24933960
TI  - [IgE-antibodies to Helicobacter pylori in children with gastroduodenal diseases
      and concomitant of allergy].
AB  - In children with chronic gastritis/gastroduodenitis (CG/CGD), ulcerative and
      erosive processes of mucous and associated allergic diseases IgM, IgA, IgG, and
      IgE to the H. pylori were determined by ELISA in the blood serum. IgM-antibodies
      to H. pylori were found in isolated cases and did not present a diagnostic
      significance. IgG-antibodies were detected in all children in the same percentage
      (40-50%), pointing indirectly to the widespread contamination by H. pylori. IgA
      antibodies to H. pylori with high frequency (83% and 57%) were found in the blood
      serum of children with the diseases of gastroduodenal zone without allergies,
      while in children with allergic pathology they were found by 3-4 times less
      (20%). IgE antibodies to H. pylori were determined in a high percentage of cases
      in healthy children (86%) and allergic children (75%), while children without
      allergy IgE antibodies were detected in the 54-65% of cases. In this study, the
      detection of IgE antibodies to H. pylori has allowed to increase the frequency of
      the diagnosis of helicobacteriosis cases in children with gastropathology by 16%
      in general and in the group of children with allergic diseases this increase
      amounted to 27.3%. Moreover, children with antihelicobacterial IgE antibodies in
      a large percentage of cases (92-94%) revealed a positive urease activity.
      Detection of serum IgE-antibodies to H. pylori in combination with other
      antibodies isotypes in children increases the diagnostic significance of
      determination of H. pylori infection and may be recommended when applying
      serodiagnosis H. pylori in children's practice, especially in children with
      allergic pathology.

PMID- 24933961
TI  - [Anemia as the only symptom of esophageal hiatal hernia of the diaphragm].
AB  - The clinical case of chronic post-hemorrhagic iron deficiency anemia in patients
      with large hiatal hernia is represented in this article.

PMID- 24933962
TI  - [Clinical usefulness of alpha-and beta-defensins in biological environments in
      patients with ulcerative colitis].
AB  - OBJECTIVE: To determine the dependence of alpha-and beta-defensins in biological
      environments and prevalence of inflammatory process, activity bei patienten
      ulcerative colitis (UC). MATERIALIEN UND METHODEN: The study was conducted on 63
      patients with moderate activity UC and 25 practically healthy people. Depending
      on the extent of the gut was isolated by the three groups of patients: group 1 (n
      = 18)--distal form, group 2 (n = 24)--left-hand localization of pathological
      process and group 3 (n = 21)--total form UC. Content of beta-defensins in the
      stool and alpha-defensins in blood by method of the immune-enzyme analysis.
      RESULTS: In the control group the level of beta-defensins in the stool was 3.7 +/
      3.2 ng/g, alpha-defensins in blood--71.7 +/- 3.8 ng/ml. In patients of group 1
      the concentration of beta-defensins in the stool was 218.5 +/- 8.2 ng/g in 2
      group--210.8 +/- 4.3 ng/g and in group 3--261.7 +/- 9.2 ng/g. Intermediate level
      a-defensins in blood match in group 1--471.8 g 9.9 ng/ml in group 2--853.5 g 9.5
      ng/ml and in group 3--479.3 +/- 6.8 ng/ ml. Regardless of the localization of
      lesions in the gut, not including beta-defensin in the stool at 2 under, the
      concentration of antimicrobial peptides in remission. CONCLUSION: Proven
      association increased expression of alpha-and beta-defensins with activity and a
      length of inflammation in the intestine at UC.

PMID- 24933963
TI  - [Immunosuppressive effect of bone marrow MSC transplantation in patients with
      ulcerative colitis with six kinds of one family autoantibodies with cross
      relationship between each other].
AB  - The 6 types of cross-linked autobodies of one family where identified during
      relapsing course of Ulcerativ Colities (UC) acompanied with deterioration of
      clinical and endoscopic activity and increasing rate of acut inflammatory phase
      (CRP, number of leukocytes and erythrocyte sedimentation rate) of the disease. On
      the background of transplantation of mesenchymal bone marrow stromal cells (BM
      MSC), and despit the identification of six types of autoantibodies to antigens of
      neutrophils, was observed moderate activity of UC and low concentration of
      autoantibodies than in immunosuppressive therapy without BM MSC transplantation.
      Discovered anti-inflammatory effect of BM MSCs transplantation in UC may be
      explained by the systemic influence of immunosuppressive effect: it is known that
      the BM MSCs inhibit dendritic cells, T-and B-lymphocytes participating in the
      immune response, activate regulatory T-cells, which produce antinflammatory
      cytokines, IL-10 and TGF-1beta, which suppress the inflammatory process.

PMID- 24933964
TI  - [Reconstruction of renal veins and imposition of vascular anastomoses in relative
      kidney transplantation].
AB  - The paper shows how to create the best ways extracorporeal reconstruction of the
      renal veins in related transplantation. It is necessary to consider the
      possibility of autoplasty at nephrectomy from a living donor, expansion of the
      distal renal vein and allow its implementation through the walls of the gonad
      donor veins. When there are several veins, the largest is used for anastomosis,
      others may be tied because of a well-developed network of intrarenal collateral
      venous outflow. With the right approach to the choice of method of angioplasty
      and its skillful implementation, taking into account the structural features of
      the vascular bed of the donor, the presence of several vessels supplying the
      kidney of a living related donor, not a contraindication to of transplantation
      and does not reduce the quality of the transplanted organ.

PMID- 24933965
TI  - [Influence of electrical stimulation of "hunger center" of the lateral
      hypothalamus and food reinforcements on myoelectrical activity of the gastro
      esophageal sphincter and stomach in rabbits under the conditions of hunger and
      satiation].
AB  - AIM: To study the combined effect of electrostimulation of "hunger center" of the
      lateral hypothalamus (LH) and food-obtaining behavior arising from it on
      myoelectrical activity of gastro-esophageal sphincter (GES) and the stomach in
      pre-fed and subjected to food deprivation animals . MATERIAL AND METHODS.
      Registration of myoelectrical GES and the stomach activity was carried out under
      free-behavior conditions in rabbits subjected to food deprivation or pre-fed
      before the experiment. It was done by means of chronically implanted electrodes
      during LH electrostimulation in the presence of food. Simultaneously using the
      web-camera the animals behavior was recorded. LH stimulation was produced by STM
      100C stimulator (USA) with implanted bipolar nichrome electrodes. Analysis of
      temporal parameters of myoelectrical activity of GES and the stomach were carried
      out by the program AcqKnowledge (USA), and statistical analysis of the data by
      the program Statistica 6. Significanse of differences between the samples was
      assessed by the U-Mann-Whitney test (p < 0.05). RESULTS: Electrostimulation of
      "hunger center" of the lateral hypothalamus in pre-fed rabbits and the rabbits
      subjected to daily food deprivation, in the presence of food causes resultant
      food behavior which is accompanied by regular generations of bursts of peak
      potentials, frequency of which is essentially different in hungry and satiated
      animals and depends on intensity of artificially induced and artificially
      reinforced food motivation. In the process of LH stimulation arising resultant
      food behavior in satiated animals is accompanied by regular generation of high
      amplitude slow electrical waves (SEW) by the muscles of lesser curvature (LC),
      the body and antrum of the stomach (AS) and this is reflected in the structure of
      temporal organization of slow electrical activity (SEA) in the form of monomodal
      distributions of SEW periods, typical of satiation state. Despite the increase in
      food motivation level, due to LH stimulation, additional entry of food into the
      stomach of satiated rabbits completely eliminates inhibitory effect of
      starvational motivational excitation on SEA of the muscles of LC, the body and
      AS. SEA alterations of the stomach muscles in hungry rabbits in the presence of
      food and thus arising of food-obtaining behavior during LH stimulation have two
      phase character. At the initial stage of food behavior in hungry animals during
      LH stimulation high extent of scaterring of the values of SEW periods generated
      by the body and AS muscles is preserved, as evidenced by the bimodal distribution
      of SEW periods characteristic of the state of hunger. In spite of food entry into
      the stomach at the 1-st phase of LH stimulation, inhibitory effect of
      artificially reinforced starvational motivational excitation on pacemaker
      activity of the stomach is retained. At the 2-nd phase of LH electrostimulation
      food reinforcement eliminates inhibitory effect of food motivational excitation
      on myoelectrical activity of pacemaker of the stomach that gives maximal rhythm
      of SEW generation to the body and AS, monomodal distributions of SEW periods
      indicate to it. CONCLUSION: lnteraction of artificially induced and artificially
      reinforced food motivational excitation with afferentation from food
      reinforcement on neurons of the central generator of deglutition pattern and
      dorsal vagal complex due to LH electrostimulation and thereby arising resultant
      food obtaining behavior is specifically reflected in patterns of myoelectrical
      activity of GES, LC, the body and AS.

PMID- 24933966
TI  - [Gastroesophageal reflux disease model].
AB  - The model of gastroesophageal reflux disease by administration of 0.2-0.25 ml of
      a 1% solution of methylene blue to fundal division of rat stomach was created.
      After 1-5 minutes electromotor activity of the lower third of the esophagus was
      observed. Mucosa staining was noted.

PMID- 24933967
TI  - [Metocinium iodide application in patients with irritable bowel syndrome].
AB  - In this article result of medication methocinium iodide (Methacin) using at
      patients with irritable bowel syndrome are observed.

PMID- 24933968
TI  - [Long-term use of capillary gastrointestinal probe for treating patients with
      giant gastric ulcer. The case report].
AB  - Conducted a successful conservative (stationary, and then outpatient) treatment
      of a patient with a giant gastric ulcer long-term use (5 months) as a basic
      treatment of capillary gastrointestinal probe.

PMID- 24933969
TI  - [Surgical nurse Ksenia Ivanovna Churkina].

PMID- 24933970
TI  - [The etiology of chronic pancreatitis].

PMID- 24933971
TI  - [Immunological criteria for evaluation of nutritional support in ulcerative
      colitis].
AB  - The article presents the data on the assessment of nutritional status, taking
      into account humoral immunologic criteria of patients with ulcerative colitis.

PMID- 24933972
TI  - [Serotonin levels and short chain fatty acids in pathogenesis of irritable bowel
      syndrome].
AB  - In 72 patients with irritable bowel syndrome (IBS) the psychological condition
      and electric activity of brain, serotonin level in plasma, short chain fatty
      acids (SFA) levels in stool were studied. In patients with IBS in aggravation of
      disease violations of central nerve system was observed. The increasing of
      reactive and personal anxious, violations in electroencephalograms and increasing
      serotonin level with modification of SFA levels were observed. Clinical,
      psychological and electroencephalographic changes, levels of serotonin and SFA is
      necessary to analyze for individual treatment program in patients with IBS.

PMID- 24933973
TI  - [On the possibilities of correction of changes of the gastrointestinal tract
      microbiota in patients with lung cancer treated receiving chemotherapy].
AB  - The aim of the study was the improvement of technologies of treatment of patients
      with the lung cancer receiving chemotherapy on the basis of using with the
      complex therapy of the combined probiotic based on the Bacillus subtilis strain.
      MATERIALS AND METHODS: 30 patients with the lung cancer receiving the first and
      second line of the first cycle of chemotherapy were included. The age of patients
      varied from 49 to 73 years, the average duration of the disease was 1 year.
      Patients of the main group (n = 21) received the combined probiotic based on the
      Bacillus subtilis strain together with the chemotherapy course. Patients of
      control group (n = 9) received only chemotherapeutic preparations. All patients
      were observed before and after treatment: the standardized inquiry for detection
      of intestinal complaints, microbiological research of feces (definition of
      qualitative and quantitative characteristics of gut microbiota), the research of
      metabolites of intestinal microorganisms in blood by the method of the gas-liquid
      chromatography - mass-spectrometry by G. A. Osipov's method. The efficiency of
      probiotic therapy was evaluated by results of studied indicators dynamics.
      RESULTS: Main symptoms of the intestinal dyspepsia were observed in patients with
      the lung cancer receiving chemotherapy such as constipation and intestinal
      microflora violations (decreased quantity of Lactobacillus, Bifidobacterium,
      Bacteroides and increased quantity of different pathogenic microorganisms). It
      was noted decreased rate of intestinal dyspepsia symptoms and improvement of
      intestinal microflora composition after the treatment course by the combined
      probiotic based on the Bacillus subtilis strain. CONCLUSION: Using of probiotic
      medicines with the chemotherapy in lung cancer patients is promising to reduce
      the frequency of gastrointestinal complaints and prevent deterioration of the gut
      microflora.

PMID- 24933974
TI  - [Reducing anxiety without deterioration of cognitive functions].
AB  - The purpose of the study--demonstrate the ability to reduce anxiety without
      having a negative impact on concentration and memory. In patients with irritable
      bowel syndrome studied anxiety, cognitive dysfunction, and memory. Patients
      received a standard basic therapy or standard treatment with psychotropic
      medication. Inclusion in the healing process valemidin significantly reduced
      anxiety in patients without a negative impact on cognitive function. IBS patients
      receiving basic therapy addition, valemidin, compared with the group of patients
      receiving only the basic therapy significantly decreased and cognitive
      dysfunction.

PMID- 24933975
TI  - [Efficiency of ursodeoxycholic acid therapy in non-alcoholic fatty liver disease
      associated with metabolic syndrome].
AB  - INTRODUCTION: Nonalcoholic Fatty Liver Disease (NAFLD) is one of the most common
      liver disease. Its prevalence is 20-30% in the population of developed countries,
      its prevalence is 26% in Russia. NAFLD is observed in many patients with
      Metabolic Syndrome. Because of the wide prevalence of this disease it is required
      to find best drugs influencing mechanisms of its development, chronicity and
      progression. MATERIALS AND METHODS: 36 patients were included to the study. Mean
      age of patients was 43 +/- 3.9 years. Patients of the main group received the
      ursodeoxycholic acid within 2 months. Patients of the control group received the
      plant origin hepatoprotective medicine. All patients before and after treatment
      were carried out the biochemical analysis of blood, the liver ultrasound
      examination, the bioimpedance body composition analysis, the microbiological
      examination of faeces, the examination of metabolites of microorganisms in the
      blood by the method of gas-liquid chromatography - mass spectrometry, developed
      by Osipov G. A. RESULTS: The reduction of hepatic transaminases, the trend to
      normalization of the lipid profile, the reduction of body weight, the reduction
      of amount of adipose tissue in the body, the increase of Bifidobacterium spp.,
      Lactobacillus spp., Enterococcus spp., the increase of levels of Bifidobacterium
      spp., Lactobacillus spp. Metabolites, the decrease of endotoxin plasma level and
      the decrease of total microbial load were observed after the UDCA treatment. The
      results of the study showed the prospectivity of the using of UDCA for NAFLD
      associated with Metabolic Syndrome.

PMID- 24933976
TI  - [Opportunities of electrogastroenterography in pediatric gastroenterological
      practice].
AB  - The aim of the investigation is to identify opportunities
      electrogastroenterography (EGEG) in the survey and individualization treatment of
      children with inflammatory diseases of the gastrointestinal tract. MATERIALS AND
      METHODS: We examined five children 10-15 years apparatus Gastroskan-HEV standard
      overlay electrodes. All children were treated with chronic gastritis in hospital.
      This diagnosis was confirmed by fibrogastrocopy. The study was conducted in the
      morning after fasting for 10-12 hours hunger for 40 minutes, and starting in 5-6
      minutes after application of the electrodes. Investigated the maximal
      fluctuations in the range 3.5-4.2 and minimal changes. RESULTS: All children
      identified acceleration motor-evacuation function of the gastrointestinal tract
      on the background of hypersecretory reaction. CONCLUSION: EGEG method is
      noninvasive, has no contraindications and is well tolerated, allowing multiple
      examine patients regardless of their age and the severity of the condition and
      correct the assigned therapy.

PMID- 24933977
TI  - [The role of pathological changes of biliopancreatoduodenal zone in development
      of postcholecystectomy syndrome].
AB  - Study of the role of biliopancreatoduodenal pathological changes in the
      development of postcholecystectomy syndrome. MATERIAL AND METHODS: Diagnostic
      complex, including endosonography has been performed in 138 patients with
      calculous cholecystitis with a significant risk of choledocholithiasis and 112
      patients with postcholecystectomy syndrome. RESULTS: The same spectrum of
      pathological changes of biliopancreatoduodenal zone in both groups was
      discovered. CONCLUSIONS: The pathological changes of biliopancreatoduodenal zone
      in patients with postcholecystectomy syndrome most likely to appear before the
      operation.

PMID- 24933979
TI  - [Serotonergic regulation of motor activity of duodenum].
AB  - Objective--find the possible role of serotonin in the regulation of motor
      activity of the duodenum. It is shown that the activation of ganglionic 5-HT4, 5
      HT3 receptors and 5-HT1--and 5-HT2 receptors of effector cells is accompanied by
      changes in electromotor activity of the intestine. Blockade of these receptors to
      varying degrees inhibit stimulatory effect of serotonin.

PMID- 24933978
TI  - [The pathological physiology of the anorectal defects, from the new concept to
      the new treatment].
AB  - PURPOSE: To determine physiology of anorectal zone in norm and anorectal
      malformations (ARM) to optimize the surgical treatment. MATERIAL AND METHODS:
      Examination of 119 patients were selected, including 65 children without
      anorectal pathology and 54 patients with ARM. We performed barium enema with
      radiopaque marker placed near the anus. The manometric study of anorectal area
      was done using intubation tube with an inflatable cuff. RESULTS: The anal canal
      was detected in all of ARM patients with perineal and vestibular fistulas, as
      well as in most of the newborns without fistula. The well innervated internal
      anal sphincter (IAS) was located in the loop of the puborectal muscle (PRM) and
      connected to the levator ani muscle (LAM) which opens the anal canal during
      defecation. Anterior and posterior sagittal approaches use IAS excision, with PRM
      damage and cutting off the LAM from IAS, which leads to incontinence and/or
      chronic constipation. CONCLUSION: We describe two surgical approaches that allow
      preservation of all elements of the anal canal resulting in a normal post
      operative continence and defecation.

PMID- 24933980
TI  - [A bezoar as a cause of dyspeptic syndrome].

PMID- 24933981
TI  - [Botkin medical dynasty].

PMID- 24933982
TI  - [Mesenchymal stem cells as perspective method of fibrosis/cirrhosis treatment].
AB  - THE PURPOSE OF THE REVIEW: Discuss the background and available results of
      transplantation of bone marrow stem cells as a promising treatment of hepatic
      fibrosis. KEY PROVISIONS: Actuality of the problem of chronic hepatitis is
      present due to their progressive course with the formation of liver cirrhosis and
      a high level of mortality. Conservative treatment of patients with decompensated
      process requires a liver transplantation that is compounded by the high
      percentage of graft reinfection in infectious hepatology. It is necessary to
      study the use of bone marrow-derived stem cells transplantation, because MSCs
      have certain therapeutic potential, low immunogenicity and the capacity for
      directional migration. In experimental models MSCs mechanisms of action are shown
      to limit the progression of liver fibrosis and stimulation of regeneration
      processes. In clinical studies good tolerability and relative safety of
      administration of autologous MSCs have reported as well as the positive effects
      on liver synthetic function, a decrease in the severity of cirrhosis on class
      Child-Pugh and MELD, reduction in overall mortality are shown. The results of our
      own prospective pilot study using autologous MSCs from bone marrow in patients
      with HCV-associated liver cirrhosis are described. CONCLUSION: MSCs can exert
      multiple synergistic effects on the hepatic stellate cells, reduce inflammation
      in the liver tissue remodeling processes and fibrogenesis. For objective evidence
      of the clinical benefits of the method, evaluation of long-term efficacy and
      safety of MSCs, as well as developing rational strategies, further clinical
      studies are required.

PMID- 24933983
TI  - [Symptoms of gastroesophageal reflux disease and associated factors in
      adolescents: population survey].
AB  - OBJECTIVES: Gastroesophageal reflux (GER) is frequent among the general
      population affecting 10-20% of adults. However, there is a notable lack of
      epidemiological data describing prevalence of GER in children. The aims of the
      present study were to assess the prevalence of GER symptoms (GERS) in adolescents
      and to evaluate factors associated with GERS including markers of H. pylori
      infection. METHODS: All school students in grades 9-11 in four randomly selected
      secondary schools in Novosibirsk participated (449 adolescents, 189 boys, 260
      girls aged 14-17). They completed the Bowel Disease Questionnaire, life-style
      questionnaire, and sera were tested for antibodies against Helicobacter pylori
      infection. RESULTS: Overall, 60% of adolescents experienced GERS (heartburn
      and/or acid regurgitation) over the previous year. GER symptoms on a monthly
      basis were reported by 22% of students, weekly GERS were reported by 9% of
      adolescents with the same frequency in both genders. GERS were related to family
      history of dyspepsia or GER, mother's lower educational attainment, overweight,
      unhealthy eating patterns, alcohol consumption, smoking, and H. pylori infection,
      as well as concomitant dyspepsia and irritable bowel syndrome. The majority of
      associations were more prominent in girls. Visiting a physician, endoscopic
      study, and school absenteeism were reported in the last year more frequently by
      adolescents with GERS vs those without GERS. CONCLUSIONS: Gastroesophageal reflux
      symptoms are frequent among the adolescent population and result in frequent use
      of health care resources. Some precipitated factors found in this study are
      modifiable and may be corrected in adolescent population.

PMID- 24933984
TI  - [Clinical and endoscopic characteristics of changes in the esophagogastroduodenal
      zone in patients with asthma].
AB  - The aim of research was to study the frequency and character of clinical
      endoscopial disturbances in gastroduodenal zone at 140 BA patients at different
      regimen of GKS therapy. The high frequency of GERD in BA patients at GKS therapy
      was established. The dependence of main respiratory simptoms of BA on GEFR, the
      intencity of cough and dyspnea were found out. Presence of GEFR at BA patients
      deteriorates patency of airways.

PMID- 24933985
TI  - [State of mucosal barrier of the stomach after Helicobacter pylori eradication
      and ulcer healing in patients with duodenal ulcer disease].

PMID- 24933986
TI  - [Abnormal calcium metabolism in the remote period after bariatric surgery].
AB  - Calcium metabolism in the long-term period after bariatric surgery is reviewed in
      the present article. The study of calcium metabolism parameters and vitamin D
      status was performed in The Endocrinology Research Center. Morbidly obese
      patients (BMI > 40) were included in the 1st group (n = 22), patients who
      underwent biliopancreatic diversion for morbid obesity (n = 23) were included in
      the 2nd group, healthy normal weight controls (n = 22) were included in the 3rd
      group. 25 (OH) D level was different in the 3 groups (p < 0.001). Vitamin D
      deficiency prevailed in morbidly obese patients compared to healthy controls (p =
      0.007). Elevated parathyroid hormone (PTH) level was found in 4 (18%) morbidly
      obese patients, in 12 (52%) operated patients. Not a single case of PTH over
      reference interval was found in the controls. The frequency of secondary
      hyperparathyroidism was significantly higher in the operated patients.

PMID- 24933987
TI  - [Results of dynamic observation of patients with polyps in the stomach].
AB  - This work is based on the analysis of data doing 409 patients with polyps in the
      stomach. Among them 200 men (48.9%) and 209 women (51.1%) aged 18 to 91 years.
      The average age of men was 67.4 years, and women 66.8 years. All these patients
      were find 1034 neoplasms of various sizes. At all of this patients polyps were
      identified on a background of chronic gastritis, as a rule, has the character of
      atrophic process. Histological research was conducted 775 (74.6%) polyps, of
      which focal hyperplasia and hyperplastic polyps detected in 49% of cases, and
      adenomas in 51% (including adenomas with varying degrees of dyspiasia, and
      prostatic adenocarcinoma cells). Endoscopic polypectomy performed 367 patients,
      and the remaining 42 was merely the dynamic monitoring of the identified
      entities. In 79 (28.8%) patients after polypectomy noted relapse formations and
      in 10 cases (3.65%) diagnosed with cancer in the intervention area. 4 (0.98%)
      patients from 409 cancer in polyps detected during the initial survey and in 4
      patients the cancer originated in the not associated with polyps of stomach. As a
      result of the research of the dependence of the size of neoplasms on the nature
      of destruction and histological structure. For most existing polyps
      characteristic of the stability of their morphological structure and the absence
      of its transformation.

PMID- 24933988
TI  - [24-hour combined pH-impedance measurement in differential diagnosis of non
      erosive reflux disease and functional gastroesophageal disorders].
AB  - AIM OF INVESTIGATION: To study potentials of 24-hour combined pH-impedance
      measurement in differential diagnosis of nonerosive reflux disease and functional
      gastroesophageal disorders. MATERIALS AND METHODS: Overall 60 patients with
      heartburn, belch and epigastric discomfort were investigated. All patients
      underwent esophagogastroduodenoscopy (EGDS), X-ray examination of upper
      gastrointestinal tract, 13C-urea breath test, 24-hour combined pH-impedance
      measurement. RESULTS: Esophagitis grade 2-4 was diagnosed in 11 (18.3%) of 60
      cases. In 49 (81.7%) no pathological changes were identify at EGDS and X-ray
      examination of upper gastrointestinal tract. Of them in 20 (33.3%) cases
      nonerosive reflux disease was revealed using 24-hour combined pH-impedance
      measurement. In 29 (48.3%) cases with the same clinical symptoms pH-impedance
      measurement data did not differ from normal, suggesting this group as group of
      patients with functional gastroesophageal disorders. CONCLUSION: 24-hour combined
      pH-impedance measurement is the most exact method which allows to identify
      gastroesophageal reflux episodes. On this basis in some cases it is possible to
      differentiate nonerosive reflux disease and functional gastroesophageal
      disorders. Application of pH-impedance measurement allows to recommend its
      introduction in wide clinical practice.

PMID- 24933989
TI  - [Serum metabolome by gas chromatography-mass spectrometry (GC-MS) in patients
      with ulcerative colitis and celiac disease].
AB  - Metabolomics is the emerging science of measurement and analysis of metabolome-
      the complete set of low molecular weight compounds in a cell, tissue, organ or
      whole organism. One of the aims of metabolomics is to research the response of an
      organism to a pathophysiological insult by measuring the concentrations of small
      molecule metabolites in biofluids and tissues and its dynamics. Intestinal
      microbiota is most probably involved in the development and maintenance of
      autoimmune inflammation in ulcerative colitis and celiac disease. Gas
      chromatography-mass spectrometry (GC - MS) of serum generates comprehensive
      metabolic profiles, reflecting integrated human (systemic) and gut microbial
      metabolism which may be altered in disease states. The aim of this study was to
      investigate GC - MS-based serum metabolomic profiles in UC and CD patients. Serum
      metabolic profiles were collected from 75 individuals: 20 patients with mild
      moderate active UC, 35 CD patients, and 20 healthy controls (HC). We
      characterized 84 serum metabolites by use GC-MS. 18 metabolites at least have a
      combined (human + microbial) origin. In serum of UC patients, phenylacetic acid
      (PAA), 4-hydroxyphenylacetic acid (4-HPAA), 3-indolylacetic acid (IAA), succinic
      acid (SA) and fumaric acid (FA) were the metabolites most prominently increased,
      whereas 3-phenylpropionic acid (PPA) was significantly decreased. Serum of CD
      patients showed significant increases in IAA, 3-indolepropionic acid (IPA), SA
      and FA. Increased serum levels of succinic acid suggest its possible damaging
      effect on intestinal mucosa especially in ulcerative colitis. Orally administered
      butyrate + inulin as supplement to mesalazine in UC or gluten free diet in CD was
      effective in reducing disease activity with a marked improvement of serum
      metabolomic profiles (including SA reduction) and gut microbiota in both
      diseases. There were no any adverse events.

PMID- 24933990
TI  - ["High" and "low" gastric ulcers in posthelicobacterial era--is this division
      vital?].
AB  - AIM OF INVESTIGATION: To specify etiopathogenetical characteristics of the
      disease in case of "high" and "low" gastric ulcers. MATERIALS AND METHODS: 96
      patients with relapse of gastric ulcer disease (GUD) were examined, median age 41
      +/- 3.1 years, 71.9% of male patients, 28.1% of female patients. The first group
      included 58 patients with "high" ulcer, the second included 38 patients with
      pyloroantral ulcer. All patients underwent esophagogastroduodenoscopy and 24-hour
      intragastric pH-metry prior to the prescription of antisecretory therapy. The
      results of the examination were compared with data of 100 healthy subjects.
      RESULTS: Intragastric acidity in case of "high" ulcers, by value of fundal and
      antral pH and its circadian dynamics, was comparable to that of the healthy
      people. By the frequency of duodenogastral reflux (DGR) close to normal the total
      duration was significantly higher because of considerable increase of portion of
      long and high refluxes. High acidity in corpus and antral region, absence of the
      normal daily variations, significant increase of night acidity, decrease of DGR
      frequency and duration were noted by "low" gastric ulcers. CONCLUSIONS: In case
      of "high" localization of gastric ulcer normal acidity production and unusual
      high and enduring duodenogastral refluxes are revealed more often; combination of
      high hyperacidity and pronounced depression of duodenogastral reflux are seen in
      case of pyloroantral ulcer.

PMID- 24933992
TI  - [Principal characteristics of the endoscopic programmed hemostasis in ulcerative
      gastroduodenal bleedings in patients with high operational-anesthesiological
      risk].
AB  - Application of the endoscopic programmed hemostasis for patients with ulcer
      gastroduodenal bleedings and with high operational-anesthetic risk provided
      metabolic rehabilitation (5% solutions of glucose and ascorbic acid) for the
      purpose of prevention of recurrence of the bleedings which have arisen after a
      hemostasis at 5.5% of patients.

PMID- 24933991
TI  - [Endoscopic treatment of chemical burns to the stomach with mucosa ulceration and
      necrosis].
AB  - The prevalence of acute poisoning with caustic substances in Russia is higher
      than in other countries and is reported by different authors as accounting for 10
      32% cases among the patients admitted to acute poisoning treatment centres.
      Especially unfavorable prognosis is considered for necrotizing burns to the
      stomach that increase the risk of severe complications leading to disability of
      patients. The study aimed at improving the treatment of necrotizing chemical burn
      to the stomach by the infusion of a 5% Mexidole solution into the edges of a burn
      lesion at different stages of the treatment course. The paper presents the
      outcomes of patients who sustained chemical burns to the stomach with mucosa
      ulceration and necrosis, and provides an assessment of early endoscopic treatment
      effect.

PMID- 24933993
TI  - [Dynamics of ultrastructural organization of liver cells in experimental
      peritonitis].
AB  - In the experiment on Wistar rats by methods of light and electron microscopy an
      ultrastructural disorders of the liver cells in various stages of peritonitis
      were investigated. It was shown that the reactive phase of experimental
      peritonitis associates with dystrophic changes of the hepatocytes and the
      endotheliocytes of sinusoids. These reversible changes are explained by an
      adaptive response of cells to inflammation. In the toxic and especially in the
      terminal stages of peritonitis in submicroscopical architectonics of the
      hepatocytes, Kupffer cells and sinusoidal endotheliocytes, along with dystrophic
      changes appear destructive violations of organelles of hepatic cells that
      acquired an irreversible character. The proposed model let description of
      ultrastructural and functional disorders of the liver cells at different stages
      of peritonitis.

PMID- 24933994
TI  - [Hepatoprotectors in treatment of alcoholic liver disease].
AB  - The best hepatoprotective effect has combined appointment Essentiale forte N,
      Heptral and Apilak at rats with chronic alcohol intoxication. Use of these drugs
      is characterized by minor morphological changes in structure of liver and
      constant biochemical parameters.

PMID- 24933995
TI  - [Fecal calprotectin in complex diagnostics of intestinal diseases].
AB  - The review of evidential base is presented in article about a place of a
      noninvasive laboratory method--dough on Calprotectin in complex diagnostics of
      diseases of intestines.

PMID- 24933996
TI  - [Pseudomembranous colitis: pathogenesis, prevention, treatment].
AB  - The article reviews a pathogenesis of Pseudomembranous colitis. Questions of
      prevention and treatment of Clostridium difficile--associated diarrhea are shown
      by the Evidence-based medicine. There is an accent on the rational prescription
      of antibiotics.

PMID- 24933997
TI  - [Clinical case of a combination of ulcerative colitis and alopecia areata].
AB  - Extraintestinal manifestations of inflammatory bowel diseases (IBD) are common in
      both ulcerative colitis and Crohn's disease. Dermatological manifestations have
      been reported in one-third of all extraintestinal manifestations of IBD. Erythema
      nodosum and pyoderma gangrenosum are the most frequently described in the
      literature. There is no data on the development of alopecia as a cutaneous
      manifestation of IBD in most of studies. A clinical case of combination of
      ulcerative colitis and alopecia in young woman is presented in the article. There
      are several possible causes of alopecia in patients with IBD, such as nutritional
      deficiencies, side effects of medications or autoimmune alopecia. Most often
      there is no correlation between the severity of clinical bowel manifestations and
      other organs involvement, and response to therapy. So the combination of alopecia
      with IBD, in particular ulcerative colitis, confirms the importance of autoimmune
      mechanisms in genesis of these diseases.

PMID- 24933999
TI  - [VIth Latvian Gastroenterology Congress with international participation (Riga,
      Latvia, 7-8 December, 2013].

PMID- 24933998
TI  - [The regular European bridging-meeting in gastroenterology (Berlin, 15-16
      November 2013)].

PMID- 24934000
TI  - Our story: transforming health care through philanthropy.

PMID- 24934001
TI  - As I see it: I believe.

PMID- 24934002
TI  - Four critical success factors.

PMID- 24934003
TI  - Finding and keeping good staff.

PMID- 24934004
TI  - Getting over the overhead myth.

PMID- 24934005
TI  - Simpler is usually better.

PMID- 24934006
TI  - A remember-know analysis of the semantic serial position function.
AB  - Did the serial position functions observed in certain semantic memory tasks
      (e.g., remembering the order of books or films) arise because they really tapped
      episodic memory? To address this issue, participants were asked to make "remember
      know" judgments as they reconstructed the release order of the 7 Harry Potter
      books and 2 sets of movies. For both classes of stimuli, the "remember" and
      "know" serial position functions were indistinguishable, and all showed the
      characteristic U-shape with marked primacy and recency effects. These results are
      inconsistent with a multiple memory systems view, which predicts recency effects
      only for "remember" responses and no recency effects for "know" responses.
      However, the data were consistent with a general memory principle account: the
      relative distinctiveness principle. According to this view, performance on both
      episodic and semantic memory tasks arises from the same type of processing: Items
      that are more separated from their close neighbors in psychological space at the
      time of recall will be better remembered.

PMID- 24934007
TI  - How plausible is it that conscious control is illusory?
AB  - Findings in a number of neuropsychological studies involving reports of decisions
      to initiate spontaneous movement (e.g., Fried, Mukamel, & Kreiman, 2011; Libet,
      Gleason, Wright, & Pearl, 1983; Soon, Brass, Heinze, & Haynes, 2008) are often
      interpreted as putting in question the reality of conscious control and, by
      extension, the time-honored concept of free will. I suggest that several problems
      with the basic paradigm used by most such studies, elaborated on in some recent
      articles (prominently Miller, Shepherdson, & Trevena, 2011, and Schurger, Sitt, &
      Dehaene, 2012), as well as some other arguments, raise doubt that conscious
      control is in fact a gratuitous byproduct of preconscious brain activity.

PMID- 24934008
TI  - Cardiovascular change during encoding predicts the nonconscious mere exposure
      effect.
AB  - These studies examined memory encoding to determine whether the mere exposure
      effect could be categorized as a form of conceptual or perceptual implicit
      priming and, if it was not conceptual or perceptual, whether cardiovascular
      psychophysiology could reveal its nature. Experiment 1 examined the effects of
      study phase level of processing on recognition, the mere exposure effect, and
      word identification implicit priming. Deep relative to shallow processing
      improved recognition but did not influence the mere exposure effect for nonwords
      or word identification implicit priming for words. Experiments 2 and 3 examined
      the effect of study-test changes in font and orientation, respectively, on the
      mere exposure effect and word identification implicit priming. Different study
      test font and orientation reduced word identification implicit priming but had no
      influence on the mere exposure effect. Experiments 4 and 5 developed and used,
      respectively, a cardiovascular psychophysiological implicit priming paradigm to
      examine whether stimulus-specific cardiovascular reactivity at study predicted
      the mere exposure effect at test. Blood volume pulse change at study was
      significantly greater for nonwords that were later preferred than for nonwords
      that were not preferred at test. There was no difference in blood volume pulse
      change for words at study that were later either identified or not identified at
      test. Fluency effects, at encoding or retrieval, are an unlikely explanation for
      these behavioral and cardiovascular findings. The relation of blood volume pulse
      to affect suggests that an affective process that is not conceptual or perceptual
      contributes to the mere exposure effect.

PMID- 24934009
TI  - Correction of false memory for associated word lists by collaborating groups.
AB  - Collaborative inhibition is often observed for both correct and false memories.
      However, research examining the mechanisms by which collaborative inhibition
      occurs, such as retrieval disruption, reality monitoring, or group filtering, is
      lacking. In addition, the creation of the nominal groups (i.e., groups
      artificially developed by combining individuals' recall) necessary for examining
      collaborative inhibition do not use statistical best practices. Using the Deese
      Roediger-McDermott paradigm, we examined percentages of correct and false
      memories in individuals, collaborative interactive groups, and correctly created
      nominal groups, as well as the processes that the collaborative interactive
      groups used to determine which memories to report. Results showed evidence of the
      collaborative inhibition effect. In addition, analyses of the collaborative
      interactive groups' discussions found that these groups wrote down almost all
      presented words but less than half of nonpresented critical words, after
      discussing them, with nonpresented critical words being stated to the group with
      lower confidence and rejected by other group members more often. Overall, our
      findings indicated support for the group filtering hypothesis.

PMID- 24934010
TI  - The phenomenology of lucid dreaming: an online survey.
AB  - In lucid dreams the dreamer is aware that he or she is dreaming. Although such
      dreams are not that uncommon, many aspects of lucid dream phenomenology are still
      unclear. An online survey was conducted to gather data about lucid dream
      origination, duration, active or passive participation in the dream, planned
      actions for lucid dreams, and other phenomenological aspects. Among the 684
      respondents who filled out the questionnaire, there were 571 lucid dreamers
      (83.5%). According to their reports, lucid dreams most often originate
      spontaneously in adolescence. The average lucid dream duration is about 14
      minutes. Lucid dreamers are likely to be active in their lucid dreams and plan to
      accomplish different actions (e.g., flying, talking with dream characters, or
      having sex), yet they are not always able to remember or successfully execute
      their intentions (most often because of awakening or hindrances in the dream
      environment). The frequency of lucid dream experience was the strongest predictor
      of lucid dream phenomenology, but some differences were also observed in relation
      to age, gender, or whether the person is a natural or self-trained lucid dreamer.
      The findings are discussed in light of lucid dream research, and suggestions for
      future studies are provided.

PMID- 24934011
TI  - Explaining the gender difference in nightmare frequency.
AB  - A recent meta-analysis showed a robust gender difference in nightmare frequency
      of medium effect size in adolescents and young adults: Women tend to report
      nightmares more frequently than men. The present study, carried out in an
      unselected student sample, indicates that 2 factors mediate the gender difference
      in nightmare frequency: neuroticism and overall dream recall frequency. The
      effect of neuroticism on the gender difference and the finding that the gender
      difference in nightmare frequency emerges at an age of about 10 years suggest
      that gender-specific socialization processes may play an important role in
      explaining the gender differences in nightmare frequency in adolescents and young
      to middle-aged adults. This idea is supported by the previous finding that
      nightmare frequency is related to sex role orientation. However, longitudinal
      studies are necessary to validate these hypotheses.

PMID- 24934012
TI  - Exploratory and confirmatory factor analyses of probability discounting of
      different outcomes across different methods of measurement.
AB  - The present studies used exploratory and confirmatory factor analyses to explore
      the degree to which probability discounting processes are similar to delay
      discounting processes. To determine whether these processes are similar, 2
      questions were addressed: the degree to which probability discounting outcomes
      can be categorized into multiple domains (as demonstrated for delay discounting)
      and whether the inverse magnitude effect would be observed for nonmonetary
      outcomes. An exploratory factor analysis was conducted using data from the fill
      in-the-blank method (Study 1), followed by a confirmatory factor analysis using
      data from a multiple-choice method (Study 2) as a replication. These studies
      provide support for the idea that outcomes can be subdivided into multiple
      domains. Generally, the discounting rates were steeper for tangible outcomes than
      nontangible outcomes, and a magnitude effect was observed that was consistent
      with, rather than the inverse of, that observed for delay discounting tasks.
      Complexities related to the relationship between probability discounting
      processes and delay discounting processing are discussed.

PMID- 24934013
TI  - Impulsivity and physical aggression: examining the moderating role of anxiety.
AB  - Individuals vary in their propensity to engage in aggressive behaviors, and
      recent research has sought to identify individual differences that contribute to
      a person's propensity for physical aggression. Previous research has shown that
      impulsivity and aggression have a consistent relational pattern among many
      different samples. However, not all impulsive people will engage in aggressive
      behavior, perhaps because of other factors such as level of physiological arousal
      from anxiety. Specifically, one factor, namely physiological symptoms of anxiety
      such as those often associated with panic, may help as a predictor variable to be
      used in risk assessments or subclassification systems of aggression. Participants
      included 689 college students who completed self-report questionnaires assessing
      impulsivity, physical aggression, and anxiety. Multivariate hierarchical
      regression analyses were conducted. Greater scores on the measure of impulsivity
      were associated with higher levels of reported physical aggression. The
      interaction (impulsivity x anxiety) was not statistically significant, suggesting
      that impulsivity has the same effect on physical aggression regardless of the
      level of anxiety. There was a main effect for anxiety, which was associated with
      higher levels of reported physical aggression. Our findings may help inform
      typologies for identifying predictor variables used in risk assessment and
      treatment planning.

PMID- 24934014
TI  - Experimental evaluation of tachistoscopic measurement: a step beyond Wundt's
      criticism.
AB  - This study was designed to assess the possible systematic bias in measurements
      obtained using tachistoscopic devices from different historical periods of
      psychological research. Four different tachistoscopic devices were used for brief
      presentations of stimuli in a letter recognition task. The research sample
      consisted of 24 participants (12 female, 12 male) in a within-subject
      experimental design with complete counterbalancing of 4 conditions defined by 4
      instrument types: fall tachistoscope, tachistoscope with camera-like shutter, and
      computer-based tachistoscopes with cathode ray tube and liquid crystal diode
      display screens. The effects of experimental conditions were examined using a
      linear mixed model analysis. Our experiment demonstrated that even in
      standardized settings the type of tachistoscope used for stimulus presentation
      systematically influenced the participants' performance. We found that the lowest
      number of correctly recalled stimuli, as well as the highest number of
      erroneously recalled stimuli, was produced in the camera-like tachistoscope
      condition. Together, these findings suggest that when results from studies
      involving tachistoscopic experiments are reviewed, the unique characteristics of
      each particular instrument used must be considered carefully.

PMID- 24934015
TI  - Groups at odds over delay of ICD-1O.

PMID- 24934016
TI  - Insurers struggle to calculate rates as enrollment nears end.

PMID- 24934017
TI  - Obamacare supporters nervous about legal test of subsidies.

PMID- 24934018
TI  - Nonsurgical heart valve procedure spurs cost concerns.

PMID- 24934019
TI  - The patient as the designer.

PMID- 24934020
TI  - Hot hiring areas driven by healthcare industry changes.

PMID- 24934021
TI  - State plans for dual-eligibles face tough challenges.

PMID- 24934022
TI  - Blocked on a metaphor.

PMID- 24934023
TI  - Feds shouldn't mandate wider networks.

PMID- 24934024
TI  - Why don't all health plans work like Castlight?

PMID- 24934025
TI  - Broadening ventilator surveillance measures improves care.

PMID- 24934026
TI  - Urban remedy.

PMID- 24934028
TI  - Country doctor.

PMID- 24934027
TI  - Roadside attraction.

PMID- 24934029
TI  - Red alert!

PMID- 24934030
TI  - ["Odd" ECG in chest pain. Is the patient healthy or ill? Situs inversus].

PMID- 24934031
TI  - [Mood picture about the small novella. "Family practitioner EBM forces
      cheating"].

PMID- 24934032
TI  - [Clarifications in the new uniform federal contract are agreed upon].

PMID- 24934033
TI  - [Who may treat and claim settlement for occupational accidents?].

PMID- 24934034
TI  - [Osteopathy as an "independent healing profession". Should balneology specialists
      treat patients independently? ].

PMID- 24934035
TI  - [Formerly this was almost the rule. Why are the elderly no longer receiving
      digitalis before an operation?].

PMID- 24934036
TI  - [2 new simultaneous hypertension guidelines from the USA. Relaxed therapy goals
      reduce medication for many patients].

PMID- 24934037
TI  - [Therapy refractory hypertension. Catheter intervention instead of pills: really
      a good option?].

PMID- 24934038
TI  - [Clostridium associated diarrhea. Feces of healthy probands eliminates the
      troublesome intestinal pathogen].

PMID- 24934039
TI  - [Cochrane reviews. Does water help control the common colds?].

PMID- 24934040
TI  - [Anorexia - sarcopenia -cachexia. Life threatening loss of appetite].

PMID- 24934041
TI  - [Inhaled corticosteroids. Essential in asthma, problematic in COPD].

PMID- 24934042
TI  - [Pain therapy in geriatric patients. "Old age is not an analgesic!" (interview by
      Dr. Elke Oberhofer)].

PMID- 24934043
TI  - [Female sex hormones. Good or bad for blood vessels?].

PMID- 24934044
TI  - [Progressive change in disposition is puzzling. Not a case for the psychiatrist].

PMID- 24934045
TI  - [Sudden cardiac death in children and adolescents. Hypertrophic cardiomyopathy is
      probably not the cause?].

PMID- 24934046
TI  - [Answer from Dr. Gross].

PMID- 24934047
TI  - [Control of recurrence with CEA and CT after colon cancer operation].

PMID- 24934048
TI  - [What is the actual cause of death of multiple sclerosis patients?].

PMID- 24934049
TI  - [Alzheimer dementia: why therapy comes too late].

PMID- 24934050
TI  - [Prednisolone injections improve carpal tunnel syndrome].

PMID- 24934051
TI  - [Does vitamin D3 fail to protect against influenza after all?].

PMID- 24934052
TI  - [Subarachnoid hemorrhage easily recognized].

PMID- 24934053
TI  - [Risks related to intramuscular and subcutaneous injections].

PMID- 24934054
TI  - [Emergency checklist: hypothermia].

PMID- 24934055
TI  - [Sexuality during pregnancy and after childbirth].

PMID- 24934056
TI  - [Gastrointestinal bleeding under treatment with new oral anticoagulants].

PMID- 24934057
TI  - [Treatment of migraine in pregnancy, in patients with comorbidities and in
      elderly people].

PMID- 24934058
TI  - [Tendon avulsion of the pelvis--diagnostics and therapy].

PMID- 24934059
TI  - [Pay more attention to hepatic encephalopathy].

PMID- 24934060
TI  - [Naturopathic management of chronic wounds].

PMID- 24934061
TI  - [Herbal medicines alternative to synthetical medicines].
AB  - Herbal pharmaceuticals in medical practice are similarly used as chemically well
      defined drugs. Like other synthetical drugs, they are subject to pharmaceutical
      legislature (AMG) and EU directives. It is to differentiate between
      phytopharmaceuticals with effectiveness of proven indications and traditional
      registered herbal medicine. Through the Health Reform Act January 2004 and the
      policy of the Common Federal Committee (G-BA)on the contractual medical care from
      March 2009--with four exceptions--Non-prescription Phytopharmaka of the legal
      Health insurance is no longer (SHI) refundable and must be paid by the patients.
      The result is that more and more well-established preparations disappear from the
      market. This article gives an overview of practical relevant indications for
      herbal medicines, which according to its licensing status, the scientific
      assessment by the Cochrane Collaboration and the Institute for Quality and
      Efficiency in Health Care (IQWiG) and evidence-based Medicine (EBM)/ meta
      analyzes as an alternative to synthetics can be used.

PMID- 24934062
TI  - [Functional heartburn--update 2013].
AB  - Functional heartburn is a frequent disease which should be considered when
      heartburn does not respond to proton pump inhibitor (PPI) treatment. Functional
      heartburn is defined in the Rome-III-criteria. Differential diagnoses like
      gastroesophageal reflux disease (GERD), non erosive reflux disease (NERD) and
      hypertensive esophagus are diagnosed employing an endoscopy and a 24h-pH-study.
      Since clinical trials are lacking, treatment approaches are empirical. Successful
      treatment includes adequate information of the patient, identification of the
      cardinal symptom and setting of realistic goals.

PMID- 24934063
TI  - [Height vertigo: epidemiology and phenomenology. Results of a representative
      epidemiological study and a survey among members of the German Alpine
      Association].

PMID- 24934064
TI  - [Caffeine in analgesics--myth or medicine?].
AB  - Caffeine as an analgesic adiuvant has been discussed for many years. In a recent
      Cochrane review based on 19 studies with a total of 7238 patients, caffeine
      enhanced the efficacy of paracetamol, ibuprofen or aspirin with a number needed
      to treat (NNT) of about 16, comparable to the effect of doubling the dose of the
      primary analgesic, reported by other authors. Analgesia by caffeine is best
      explained by antagonism at adenosine receptors. Recent studies confirmed a
      favourable tolerability profile of caffeine when consumed in "normal" quantities
      (e.g. 300 mg or about 3 cups of coffee per day), including possible
      cardiovascular risks, effects on bone density, and exposure in pregnancy.
      Beneficial effects are known,e.g.,in Parkinson's disease and liver cirrhosis and
      fibrosis. Caffeine remains an analgesic adiuvant with a favourable risk-benefit
      balance.

PMID- 24934065
TI  - [2-week efficacy and tolerability of flupirtine MR and diclofenac in patients
      with acute low/back pain--results of a post-hoc subgroup analysis of patient
      level data from four non-interventional studies].
AB  - BACKGROUND: Current restrictions in use of flupirtine-containing medicines for a
      maximum of 14 days endorsed by the European Medicines Agency were followed by
      uncertainty/ambiguity of its analgesic efficacy for the treatment of acute
      low/back pain. METHODS: Post-hoc selection of patient-level data from non
      interventional studies with flupirtine MR and diclofenac with respect to patient
      age (> or = 18 years), duration of treatment (14 +/- 2 days), indication
      (acute/subacute low/back pain) and first-line use. Primary endpoint: average 24
      hr. pain intensity; secondary endpoints: pain-related disabilities in daily life,
      30/50/70% response with respect to pain and pain-related restrictions, frequency
      of untoward side effects/treatment emergent adverse events. RESULTS: 318/31
      patients treated with flupirtine MR/diclofenac fulfilled the inclusion criteria
      for this subgroup analysis. Starting from comparable demographic and baseline
      characteristics both treatments were followed by significant effects (p < 0.001).
      Subgroup comparisons revealed superior effects for flupirtine MR vs. diclofenac
      for pain relief (p = 0.001), improvement of pain-related restrictions in daily
      life (p = 0.023), and gastrointestinal/overall tolerability (p < 0.001).
      CONCLUSIONS: Even for short-term use in patients suffering from muscle-related
      acute low/back pain, flupirtine MR is superior effective and tolerated compared
      with the nsaid diclofenac.

PMID- 24934066
TI  - An evaluation of a global vitamin and mineral nutrition surveillance system.
AB  - Evaluation of public health surveillance systems is essential to ensure that
      problems of public health importance are monitored efficiently and effectively.
      The WHO's Vitamin and Mineral Nutrition Information System (VMNIS) was evaluated
      from the perspective of public health surveillance and informatics. Steps
      included: engaging the stakeholders of the evaluation; describing the
      surveillance system; focusing the evaluation design; gathering credible evidence
      regarding system performance; justifying and stating conclusions and
      recommendations, and sharing lessons learned from the evaluation. Following this
      assessment, WHO has begun major efforts to upgrade and expand the VMNIS and now
      the database is more flexible and efficient. The database evaluation summarized
      in this paper provides a good example of how public health evaluation frameworks
      can lead to improved surveillance and enhanced information systems, thus making
      progress toward the ultimate goal of improving public health.

PMID- 24934067
TI  - [Nutritional status and food intake of populations from high altitude regions of
      the Northwest of Argentia].
AB  - The purpose of this work was to study the nutritional status and food intake of
      Andean populations of Northwest ofArgentine. A cross-sectional nutritional survey
      was carried out in representative samples of populations of highland from
      Argentine. Also anthropometric measurements, a food intake, a semi-quantitative
      food frequency questionnaire were performed and recorded. Stunting (height-for
      age Z-score < -2 standard deviations) was the main nutritional problem in
      children and adolescents in the area of Puna and Quebrada regions. While
      overweight and obesity, evaluated by BMI> 85th and 95th percentile respectively,
      were the main nutritional problems among adolescents in the Valleys. Adult
      populations showed higher prevalence of overweight and obesity according to BMI
      determined. These are important risk factors for cardiovascular and chronic
      diseases.Usually the typical composition of the main food dish of regions has a
      base of rice, pasta, flour or corn, accompanied by tubers or eggs, or a few
      vegetables and beef. This dish varies little from one day to another,
      constituting a monotonous diet with a high intake of sugar (sugary drinks and
      sweets) and refined grains. Results suggest that these populations would be in
      early stages of nutritional transition and could be the starting point to promote
      them healthier food consumption and a diet less monotonous. It would be
      recommendable reincorporate native products of the region.

PMID- 24934068
TI  - At risk or not: comparing normative and criterion-referenced body mass index
      standards among Mexican American children.
AB  - Most childhood obesity research has classified participants by normative
      standards for Body Mass Index (BMI) through population percentiles or values
      corresponding to overweight adults (World Health Organization (WHO), Centers for
      Disease Control and Prevention (CDC) and the International Obesity Task Force
      (IOTF)). In 2006, criterion-referenced standards (FitnessGram) were developed
      (revised in 2010) which directly associate BMI values with adverse health
      outcomes. This study assessed agreement between normative and criterion
      referenced standards. Participants included 653 Mexican American 3rd to 5th
      graders living in the U.S.-Mexico border area who participated in a health
      promotion project. At baseline, agreement was compared between normative and
      criterion-referenced classifications. At follow-up, agreement between
      classifications on changes (e.g., from overweight to healthy weight) was
      assessed. According to FitnessGram standards, 53.0% of participants were
      overweight or obese at baseline. Compared to FitnessGram, the IOTF and CDC
      standards classified 15% fewer participants as obese/high risk. The WHO standards
      were closely related to FitnessGram (kappa=.925) and showed significantly greater
      agreement with FitnessGram than the CDC (kappa=.925 versus 0.722, p < .001) and
      IOTF standards (kappa=.925 versus .682, p < .001). Compared to the FitnessGram
      (8.9%), the WHO and CDC (8.6%) were similar, but IOTF standards lower (6.5%) in
      how many children improved following the health program. Despite acceptable
      agreement between the different indices, several normative classifications may
      underestimate the proportion of children who are at risk for BMI-related adverse
      health consequences.

PMID- 24934069
TI  - [Glycemic response to consumption of a cereals and legume (Phaseolus vulgaris)
      bar on healthy individuals].
AB  - The objective of this work was to formulate a cereals and legume (Phaseolus
      vulgaris) bar and assess its impact on the glycemic response of healthy
      individuals, in order to contribute to the healthy food supply beneficial to
      consumers. A mixture of cereals (corn and oats) and different percentages (20 and
      30%) of Phaseolus vulgaris was used to formulate the bar. Additionally, a legume
      cereal bar without legumes (bar control) was prepared. The bar with 30% of
      Phaseolus vulgaris was selected through sensory evaluation, being scored with
      better flavor and texture. This combination of cereals and legumes aminoacid
      improves complementation and reaches the formulation criteria previously
      established. Chemical characterization indicated a higher protein content in the
      bar with 30% of Phaseolus vulgaris (13.55%) relative to the bar control (8.5%).
      The contents of fat, ash and dietary fiber did not differ between the two bars
      evaluated. However, the soluble fiber and resistant starch of the selected bar
      was a 32.05% and 18.67%, respectively, than in the control bar; this may
      contribute to decreasing the rate of glucose uptake. The selected bar presented a
      low glycemic index (49) and intermediate glycemic load (12.0) in healthy
      volunteers, which could lead to a possible reduction in the rate of absorption of
      glucose into the bloodstream, associated with a carbohydrate content of slow
      absorption. This bar represents a proposal of a healthy snack for the consumer.

PMID- 24934070
TI  - [Modification of fasting blood glucose in adults with diabetes mellitus type 2
      after regular soda and diet soda intake in the State of Queretaro, Mexico].
AB  - The objective of the study was to compare the modification of fasting blood
      glucose in adults with diabetes mellitus type 2 after intake of regular soda and
      diet soda. We conducted a randomized clinical trial in clinics of Instituto
      Mexicano del Seguro Social in Queretaro, Mexico. We included 80 patients with
      diabetes (mean weight 74.2 +/- 13.66, BMI 30.5 +/- 4.305, waist 98.2 +/- 12.9 and
      time evolution of diabetes 3.8 +/- 3.009) who were asked to come with fasting for
      8 hours and without taking any medicine before testing. They were divided into
      two groups of 40 subjects, to whom was measured fasting blood glucose after the
      ingestion of 200 ml of diet soda (with aspartame and acesulfame potassium) or
      regular soda (without sweetener) we measure glucose at 10, 15 and 30 minutes. For
      statistical analysis performed we used Student's t-test for dependent and
      independent samples, and paired t-test, and chi square test (chi2). Capillary
      glucose levels at 10 minutes were -34.52 and -25.41%, at 15 minutes -48.8 and 
      36.2% and at 30 minutes 57.75 and 43.6% of absolute and relative differences,
      with p = 0.000. In conclusion, according to the observations, diet soda doesn't
      increased blood glucose levels, with a significant difference in fasting
      decreased at 30 minutes.

PMID- 24934071
TI  - [Pre-diabetes and diabetes without association with overweight or obesity in
      Mexican youth].
AB  - The purpose of this study was to identify the prevalence of prediabetes and
      diabetes in young in new college students and the relationship of these data with
      anthropometric indexes. 3559 students took part, 2257 (61.43%) women (X 18.58
      years) and 1725 (36.59%) men (X 18.76 years). Body mass index were measured up as
      well as waist hip ratio and waist height ratio. Fasting blood glucose,
      triglycerides, total cholesterol, low and high density lipoproteins were
      determined. Odds ratio (OR) and 95% confidence intervals were determined. There
      was a high proportion of overweight-obesity combined, 42.29% women and 52.45%
      men. They were founds +/- 10% of women and men that presented glucose > 5.6
      mmol/L (prediabetes) and +/- 1% of women and men that had glucose > or = 7 mmol/L
      (diabetes). No relationship was found between this data and body mass index (OR
      0.97women and 1.08 men), waist hip ratio (OR 1,7 women and 0.8 men) or waist
      height ratio (OR 1.1 women and 1.19 men). There was elevated triglycerides in
      13.55% of women and 21.04% of men and a low level of high density lipoprotein in
      16% of women and 10% of men. We found that in these young people the predictive
      power of the three anthropometric parameters was limited to triglycerides in
      women and men (OR 2.4 and 3.86) and low high density lipoproteins in women (OR
      0.42).

PMID- 24934072
TI  - [Calcium intake and adiposity in adolescents aged 12-16 years in Guadalajara,
      Mexico].
AB  - The purpose was to evaluate the association between calcium (Ca) intake and
      adiposity in adolescents. A cross-sectional study of 125 adolescents 12 to 16
      years. Ca intake was evaluated by 24-hour recall dietary surveys and food
      frequency consumption. Adiposity was measured by anthropometric methods and
      bioelectrical impedance (BIA). The association between Ca intake and adiposity
      was identified by simple correlation and multivariate models adjusted to energy
      consumption, age, sex and menarche. Mean age of adolescents was 13.5 +/- 0.8
      years. A negative correlation was identified between Ca intake and anthropometric
      indicators weight, skinfolds, body mass index, fat mass and percentage of fat
      (the latter two by BIA and only in women). Multivariate analysis, including
      energy consumption showed no association between Ca intake and adiposity. In
      conclusion, Ca consumption does not associate with adiposity in adolescents;
      multivariate models showed that energy intake and menarche are the variables that
      show a higher association with adiposity at this stage of life.

PMID- 24934073
TI  - [Arcobacter: a foodborne emerging pathogen].
AB  - In the last three decades, several emergent diseases affecting human beings have
      been identified, most of them from infectious origin including bacterial, viral,
      parasitic and even difficult to classify as spongiform encephalopathy. Most of
      these are zoonotic as it is the case of Arcobacter, currently considered as an
      emerging and food borne pathogen, of growing importance for public health. The
      increase in the prevalence and incidence of cases associated to this bacteria as
      well as in the number of actual researches and reports, suggest that the
      infection in human beings and animals has been underestimated due to a lack in
      knowledge about this bacteria and of a standardized isolation protocols, as well
      as the use of correct identification methods and techniques. Increasing trends in
      the isolation of Arcobacter from animal derivates used as food and from samples
      taken during production processes, cause an augment in public health awareness,
      since there is little knowledge about the pathogenic potential of Arcobacter
      species and the few focused in this bacterial group, show many different
      transmission routes and host species. Given this, the objective of the present
      review is to actualize the reader in the most important characteristics of this
      bacterium, including its morphology, distribution, classification, transmission,
      association with water, food, pets and animals, as well as the laboratory
      isolation techniques, virulence factors and their antibiotic susceptibility
      patterns.

PMID- 24934074
TI  - [Bacteriostatic effect and/or xylitol bactericide of crops on Listeria
      Monocytogenes].
AB  - Listeria monocytogenes has been considered as an emerging pathogen causing
      foodborne illness. In the search for an alternate route biocontrol propagation,
      xylitol has been proposed as a possible bacteriostatic and / or bactericide.
      Xylitol is a polyol derived from the hydrogenation of xylose monosaccharide of
      importance in the pharmaceutical industry for its anti-cariogenic effect. To
      check the possible effect of xylitol as bacteriostatic and/or bactericidal
      against Listeria monocytogenes, it was determined the minimum inhibitory
      concentration (MIC), the time minimum inhibition (TMI) and minimum bactericidal
      concentration (MBC) of xylitol solutions on Listeria monocytogenes ATCC 7635. The
      agar diffusion method was applied, using xylitol solutions at concentrations of 0
      10%, respectively, for the MIC. The TMI was determined by growth curves in
      trypticase soy broth with solutions 1, 2, 3, 5, 8, 9, 10 and 20% of xylitol,
      respectively, with an initial inoculum of 108 CFU per ml of Listeria
      monocytogenes in each solution. MIC observed was the solution 1% of xylitol; the
      TMI was 10 hours to concentrations of 1 to 10% and 7 hours to apply 20% xylitol.
      It was found that xylitol has bacteriostatic power on Listeria monocytogenes (p <
      0.001), but not bactericide effect.

PMID- 24934075
TI  - Comparative efficiency of different methods of gluten extraction in indigenous
      varieties of wheat.
AB  - The present study investigated six varieties of locally grown wheat (Lasani,
      Sehar, Miraj-08, Chakwal-50, Faisalabad-08 and Inqlab) procured from Punjab Seed
      Corporation, Lahore, Pakistan for their proximate contents. On the basis of
      protein content and ready availability, Faisalabad-08 (FD-08) was selected to be
      used for the assessment of comparative efficiency of various methods used for
      gluten extraction. Three methods, mechanical, chemical and microbiological were
      used for the extraction of gluten from FD-08. Each method was carried out under
      ambient conditions using a drying temperature of 55 degrees C. Mechanical method
      utilized four different processes viz:- dough process, dough batter process,
      batter process and ethanol washing process using standard 150 mesh. The starch
      thus obtained was analyzed for its proximate contents. Dough batter process
      proved to be the most efficient mechanical method and was further investigated
      using 200 and 300 mesh. Gluten content was determined using sandwich omega
      gliadin enzyme-linked immunosorbent assay (ELISA).The results of dough batter
      process using 200 mesh indicated a starch product with gluten content of 678 ppm.
      Chemical method indicated high gluten content of more than 5000 ppm and the
      microbiological method reduced the gluten content from 2500 ppm to 398 ppm. From
      the results it was observed that no gluten extraction method is viable to produce
      starch which can fulfill the criteria of a gluten free product (20 ppm).

PMID- 24934076
TI  - Pain, coping, and sleep in children and adolescents with sickle cell disease.
AB  - PURPOSE: The study examined the relationships among pain, pain coping, and sleep,
      and assessed factors (age, gender, frequency, and intensity of pain) that affect
      pain, coping, and sleep in children with sickle cell disease (SCD). METHODS:
      Participants (66) were 39 children (M = 11.5 years) and 27 adolescents (M = 15.5
      years) with SCD who completed an electronic visual analog scale (eVAS), Pain
      Coping Questionnaire, and Pittsburg Sleep Quality Index. RESULTS: About two
      thirds of the children reported pain the previous month. No significant
      differences were found between pain and age, gender, pain intensity, or
      frequency. Most children coped with pain by seeking information, problem solving,
      seeking social support, and positive self-statements. There were significant
      negative correlations in males between worse pain severity and behavioral
      distraction and internalizing or catastrophizing. The majority (91.2%) had mild
      to severe sleep disturbances, with 18.2% requiring sleeping medication three or
      more times a week. There were no significant differences between sleep and age,
      gender, pain intensity, or frequency. CONCLUSION: Children with SCD experience
      pain that affects sleep patterns and the way they cope with pain. Nurses need to
      concurrently assess pain, coping, and sleep and promote sleep hygiene and
      positive coping strategies during pain episodes.

PMID- 24934077
TI  - Scabies.

PMID- 24934078
TI  - Hemophagocytic lymphohistiocytosis as a possible cause of prolonged fever,
      splenomegaly, and cytopenia.

PMID- 24934079
TI  - Coexistence of radioactive iodine-resistant benign struma ovarii with cervical
      primary papillary cancer of the thyroid: an unusual cause of thyroglobulin
      positive radioactive iodine-negative whole-body scans.

PMID- 24934080
TI  - Identification of a dominant gene in Medicago truncatula that restricts
      nodulation by Sinorhizobium meliloti strain Rm41.
AB  - BACKGROUND: Leguminous plants are able to form a root nodule symbiosis with
      nitrogen-fixing soil bacteria called rhizobia. This symbiotic association shows a
      high level of specificity. Beyond the specificity for the legume family,
      individual legume species/genotypes can only interact with certain restricted
      group of bacterial species or strains. Specificity in this system is regulated by
      complex signal exchange between the two symbiotic partners and thus multiple
      genetic mechanisms could be involved in the recognition process. Knowledge of the
      molecular mechanisms controlling symbiotic specificity could enable genetic
      improvement of legume nitrogen fixation, and may also reveal the possible
      mechanisms that restrict root nodule symbiosis in non-legumes. RESULTS: We
      screened a core collection of Medicago truncatula genotypes with several strains
      of Sinorhizobium meliloti and identified a naturally occurring dominant gene that
      restricts nodulation by S. meliloti Rm41. We named this gene as Mt-NS1 (for
      M.truncatulanodulation specificity 1). We have mapped the Mt-NS1 locus within a
      small genomic region on M. truncatula chromosome 8. The data reported here will
      facilitate positional cloning of the Mt-NS1 gene. CONCLUSIONS: Evolution of
      symbiosis specificity involves both rhizobial and host genes. From the bacterial
      side, specificity determinants include Nod factors, surface polysaccharides, and
      secreted proteins. However, we know relatively less from the host side. We
      recently demonstrated that a component of this specificity in soybeans is defined
      by plant NBS-LRR resistance (R) genes that recognize effector proteins delivered
      by the type III secretion system (T3SS) of the rhizobial symbionts. However, the
      lack of a T3SS in many sequenced S. meliloti strains raises the question of how
      the specificity is regulated in the Medicago-Sinorhizobium system beyond Nod
      factor perception. Thus, cloning and characterization of Mt-NS1 will add a new
      dimension to our knowledge about the genetic control of nodulation specificity in
      the legume-rhizobial symbiosis.

PMID- 24934081
TI  - Effects of impression levels and trays on the accuracy of impressions taken from
      angulated implants.
AB  - BACKGROUND AND PURPOSE: It is crucial to keep the misfit of the abutment-fixture
      unit at the lowest possible rate. There are a few controversial studies on the
      accuracy of impression making of angulated implants, and much fewer (and
      controversial) studies on the abutment-level impression technique, which is a
      convenient and clinically favorable method. Besides, there are no studies on
      comparison of sectional vs. full-arch trays. We aimed to assess these. METHODS: A
      trapezoidal model with four angulated implants installed at 20 degrees  and 30
      degrees  buccal tilts was fabricated. Forty impressions were taken from this
      model, with two groups of full-arch and sectional custom trays (n = 2 * 20), each
      divided into two subgroups of implant-level and abutment-level techniques (n = 2
      * 2 * 10 in four subgroups). Absolute and non-absolute linear and angular
      impression errors were estimated by comparing the fabricated casts with the
      model, using a coordinate measuring machine. The effects of sectional/full-arch
      trays and abutment-level and fixture-level techniques on impression accuracies
      were analyzed using one- and two-way analyses of variance (ANOVA), Tukey, Mann
      Whitney, and one-sample t-tests (alpha = 0.05, Mann-Whitney's alpha using the
      Bonferroni Bonferroni method). RESULTS: No significant differences between the
      absolute linear errors of the two trays (P = 0.100 [ANOVA]) and the two levels (P
      = 0.400 [ANOVA]) were observed. The assessment of absolute angular errors showed
      no significant differences (all P values >= 0.4 [ANOVA]). The difference between
      the linear errors in the full-arch vs. sectional trays was not significant in the
      fixture-level group (P = 0.290). However, in the abutment-level group, the linear
      error was significantly greater in the sectional tray compared to full-arch tray
      (P = 0.013, alpha = 0.025 [Mann-Whitney]). CONCLUSIONS: Using sectional trays
      might not be advantageous over full-arch trays. Sectional trays are not
      recommended for taking abutment-level impressions. The abutment-level impression
      technique is as accurate as the studied fixture-level technique. Increasing the
      angle of implants' divergence from 40 degrees  to 60 degrees  might not usually
      lead to a significant increase in the errors, particularly when using abutment
      level impressions.

PMID- 24934082
TI  - Norwegian airline passengers are not more afraid of flying after the terror act
      of September 11. The flight anxiety, however, is significantly attributed to acts
      of terrorism.
AB  - The aim of this paper is to study: (1) the prevalence of flight anxiety among
      Norwegian airline passengers; (2) situations that may be of concern during
      flights and situations not related to flying; (3) whether passengers feel more
      afraid after the terror act of September 11, 2001; and (4) whether passengers
      were more afraid in 2002 than in 1986.A questionnaire was distributed during
      domestic flights in Norway in 1986 and 2002. To asses flight anxiety, a six point
      scale was used, from 0 = not afraid at all, to 5 = always very afraid, and
      sometimes avoid flying because of that. A 10-cm visual analogue scale (VAS) was
      used to measure the degree of anxiety. There were 50.8% who were not afraid at
      all. There were 12 women (5.2%) and one man (0.4%) with flight phobia. However,
      22 (4.5%) had cancelled flights because of anxiety during the last two years.
      Situations that caused most concern during flights were turbulence and fear of
      terrorism and highjacking. After September 11, 48% were not more afraid, 38% a
      little more, 10% moderately, 3% rather much and 2% very much. The passengers,
      however, were not more afraid of flying in 2002 than in 1986. About 3% of
      Norwegian airline passengers have a flight phobia. Women are significantly more
      concerned than men. The impact of the terror act September 11, 2001 was rather
      moderate. The level of flight anxiety among Norwegian airline passengers was not
      significantly different in 2002 and 1986. 

PMID- 24934083
TI  - Do statin medications impact renal functional or oncologic outcomes for robot
      assisted partial nephrectomy?
AB  - OBJECTIVE: To evaluate if statin medications (3-hydroxyl-3-methylglutaryl
      coenzyme A [HMG-CoA] reductase inhibitors) improve either oncologic or renal
      functional outcomes for patients undergoing robot-assisted partial nephrectomy
      (RPN). PATIENTS AND METHODS: Patients undergoing RPN between March 2008 and
      October 2013 were evaluated from a prospectively maintained database for statin
      usage. The rate of perioperative acute kidney injury (AKI), as defined according
      to the RIFLE criteria, and the progression of chronic kidney disease (CKD) were
      compared between users and nonusers. Oncologic outcomes and rate of progression
      were compared between users and nonusers. RESULTS: One hundred four (31%) of 339
      patients were on statin therapy preoperatively and continued this medication peri
      and postoperatively. Statin patients were older and had higher rates of
      comorbidities, including coronary artery disease, diabetes, and hypertension
      (p<0.0001 for all).The rate of AKI in the statin (16%) and nonstatin patients
      (14%) (p=0.60) and CKD progression based on Kaplan-Meier estimates (p=0.57) were
      similar between both the groups. Subgroup analysis of the 271 (80%) patients with
      hilar clamping also had similar rates of AKI, in statin users 10% vs 12% in
      nonusers (p=0.50). Multivariate analysis of factors affecting CKD progression
      confirmed these findings. Oncologic progression was not affected by statin
      therapy (p=0.90). CONCLUSION: Statin medications do not appear to influence
      perioperative renal function following RPN, in either clamped or unclamped
      procedures. Continuation of these medications may be continued perioperatively,
      but any effect on renal functional or oncologic outcomes was not elucidated in
      this study.

PMID- 24934084
TI  - Take a closer look: biofuels can support environmental, economic and social
      goals.

PMID- 24934086
TI  - A longitudinal study of children's outside play using family environment and
      perceived physical environment as predictors.
AB  - BACKGROUND: A natural and cheap way of increasing children's physical activity is
      stimulating unstructured outside play. PURPOSE: This study examined whether
      characteristics of the family and perceived physical environment were associated
      with the duration of children's outside play. METHODS: Parents participating in
      the "Be Active, Eat Right" cluster RCT control group (N = 2007) provided
      information on potential predictors of outside play (i.e. family and perceived
      physical environment) of their 5-year-old child by questionnaire. Child outside
      play was assessed by parental reports both at five and seven years. Linear
      regression analyses, adjusted for seasonality, were performed to evaluate
      associations between potential predictors and child outside play. Linear mixed
      models were fitted to evaluate the relationship between potential predictors and
      the development of outside play over two years, with season entered as a random
      factor. RESULTS: Family environment was the strongest construct predicting child
      outside play, while parent perceived physical environment had no significant
      association with child outside play. Parental habit strength and the presence of
      rules were the strongest predictors of increased outside play. Parent perceived
      difficulty in improving child outside play was the strongest predictor of
      decreased outside play. CONCLUSION: Family environment predicted child outside
      play and not perceived physical environment. Parental rules and habit strength
      regarding improving outside play were associated with an improvement of child's
      engagement in outside play.

PMID- 24934085
TI  - Differences in beliefs and home environments regarding energy balance behaviors
      according to parental education and ethnicity among schoolchildren in Europe: the
      ENERGY cross sectional study.
AB  - BACKGROUND: To explore differences in personal and home environmental factors
      that are regarded as determinants of energy balance-related behaviors (EBRBs)
      according to parental education and ethnic background among 10-12 year old
      schoolchildren across Europe. METHODS: A school-based survey among 10-12 year
      olds was conducted in eight countries across Europe. A range of personal and home
      environment variables relevant for soft drink consumption, daily breakfast, sport
      participation and TV time was assessed by means of child report. Personal factors
      included attitude, health beliefs, and preference/liking. Home environment
      factors included parental subjective norm, modeling, support, practices and home
      availability. Children were classified based on parental education (i.e., low vs.
      high) and ethnic background (i.e., native vs. non-native). Data from 6018
      children originating from 83 schools were included in the analyses. RESULTS:
      Multilevel logistic regression analyses showed that the majority of the factors
      tested -and especially home environment variables- were more favorable among
      children from higher educated parents and from native ethnicity. None of the
      personal and home environment factors was found to be more favorable among
      children from lower educated parents or non-native ethnicity. CONCLUSIONS: The
      present study indicates that schoolchildren from lower educated and non-native
      parents across Europe have EBRB-related beliefs and are exposed to home
      environments that are less favorable for engagement in healthy EBRBs.

PMID- 24934088
TI  - NOD1 receptor is up-regulated in diabetic human and murine myocardium.
AB  - Type 2 diabetes has a complex pathology that involves a chronic inflammatory
      state. Emerging evidence suggests a link between the innate immune system
      receptor NOD1 (nucleotide-binding and oligomerization domain 1) and the
      pathogenesis of diabetes, in monocytes and hepatic and adipose tissues. The aim
      of the present study was to assess the role of NOD1 in the progression of
      diabetic cardiomyopathy. We have measured NOD1 protein in cardiac tissue from
      Type 2 diabetic (db) mice. Heart and isolated cardiomyocytes from db mice
      revealed a significant increase in NOD1, together with an up-regulation of
      nuclear factor kappaB (NF-kappaB) and increased apoptosis. Heart tissue also
      exhibited an enhanced expression of pro-inflammatory cytokines. Selective NOD1
      activation with C12-gamma-D-glutamyl-m-diaminopimelic acid (iEDAP) resulted in an
      increased NF-kappaB activation and apoptosis, demonstrating the involvement of
      NOD1 both in wild-type and db mice. Moreover, HL-1 cardiomyocytes exposed to
      elevated concentrations of glucose plus palmitate displayed an enhanced NF-kappaB
      activity and apoptotic profile, which was prevented by silencing of NOD1
      expression. To address this issue in human pathology, NOD1 expression was
      evaluated in myocardium obtained from patients with Type 2 diabetes (T2DMH) and
      from normoglycaemic individuals without cardiovascular histories (NH). We have
      found that NOD1 was expressed in both NH and T2DMH; however, NOD1 expression was
      significantly pronounced in T2DMH. Furthermore, both the pro-inflammatory
      cytokine tumour necrosis factor alpha (TNF-alpha) and the apoptosis mediator
      caspase-3 were up-regulated in T2DMH samples. Taken together, our results define
      an active role for NOD1 in the heightened inflammatory environment associated
      with both experimental and human diabetic cardiac disease. 

PMID- 24934087
TI  - Age related changes to the dynamics of contralateral DPOAE suppression in human
      subjects.
AB  - BACKGROUND: The two ears are linked with a neural pathway such that stimulation
      of one ear has a modulating effect on the contralateral cochlea. This is mediated
      by cochlear afferent neurons connecting with olivo-cochlear efferents. The
      monitoring of this pathway is easily achieved by measuring contralateral
      suppression of otoacoustic emissions, and there is some clinical value in the
      ability to assess the integrity of this pathway. An important step in an
      evaluation of clinical utility is to assess any age-related changes. Accordingly,
      in the present study we measure the dynamics of contralateral DPOAE suppression
      in a population of normal hearing subjects of different ages. METHODS: Using a
      real-time DPOAE recording method we assessed contralateral DPOAE suppression in
      95 ears from 51 subjects (age range 2-52 years). DPOAE (2f1-f2; f2 = 4.4 kHz;
      f2/f1 = 1.22) input-output functions were measured. In response to contralateral
      broadband noise, dynamic aspects of DPOAE suppression were measured, specifically
      suppression onset latency and time constants. RESULTS: An age-related reduction
      in DPOAE amplitudes was observed. Both the detectability and the degree of
      contralateral DPOAE suppression were decreased in older age groups. We find an
      age-related increase in the latency of onset of DPOAE suppression to
      contralateral stimulation, but no significant change in suppression time
      constants. CONCLUSION: Olivo-cochlear function as revealed by contralateral
      suppression of DPOAEs shows some important age-related changes. In addition to
      reduced emissions (outer haircell suppression) we find an increased latency that
      may reflect deterioration in auditory brainstem function. Regarding clinical
      utility, it is possible that the changes observed may reflect an aspect of age
      related hearing loss that has not been previously considered.

PMID- 24934089
TI  - Aortic root surgery in the United States: a report from the Society of Thoracic
      Surgeons database.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the early clinical
      outcomes of aortic root surgery in the United States. METHODS: The Society of
      Thoracic Surgeons database was queried to identify all patients who had undergone
      aortic root replacement from 2004 to early 2010 (n = 13,743). The median age was
      58 years (range, 18-96); 3961 were women (29%) and 12,059 were white (88%). The
      different procedures included placement of a mechanical valve conduit (n = 4718,
      34%), stented pericardial (n = 879, 6.4%) or porcine (n = 478, 3.5%)
      bioprosthesis, stentless root (n = 4309, 31%), homograft (n = 498, 3.6%), and
      valve sparing root replacement (n = 1918, 14%). RESULTS: The median number of
      aortic root surgeries per site was 2, and only 5% of sites performed >16 aortic
      root surgeries annually. An increased trend to use biostented (porcine or
      pericardial) valves during the study period (7% in 2004 vs 14% in 2009). The
      operative (raw) mortality was greater among the patients with aortic stenosis
      (6.2%) who had undergone aortic root replacement, independent of age. Mortality
      was greater in patients who had undergone concomitant valve or coronary artery
      bypass grafting or valve surgery (21%). The lowest operative mortality was
      observed in patients who had undergone aortic valve sparing procedures (1.9%).
      CONCLUSIONS: Most cardiac centers performed aortic root surgery in small volumes.
      The unadjusted operative mortality was greater for patients >80 years old and
      those with aortic stenosis, regardless of age. Valve sparing root surgery was
      associated with the lowest mortality. A trend was seen toward an increased use of
      stented tissue valves from 2004 to 2009.

PMID- 24934090
TI  - Ganglioside GM3 is required for caffeic acid phenethyl ester-induced
      megakaryocytic differentiation of human chronic myelogenous leukemia K562 cells.
AB  - The human chronic myelogenous cell line K562 has been used extensively as a model
      for the study of leukemia differentiation. We show here that treatment of K562
      cells with caffeic acid phenethyl ester (CAPE) induced a majority of cells to
      differentiate towards the megakaryocytic lineage. Microscopy analysis showed that
      K562 cells treated with CAPE exhibited characteristic features of physiological
      megakaryocytic differentiation, including the presence of vacuoles and
      demarcation membranes. Differentiation of K562 cells treated with CAPE was also
      accompanied by a net increase in megakaryocytic markers. The transcriptional
      activity of lactosylceramide alpha-2,3-sialyltransferase (GM3 synthase) and
      synthesis of ganglioside GM3 were increased by CAPE treatment. The promoter
      analysis of GM3 synthase demonstrated that CAPE induced the expression of GM3
      synthase mRNA via activation of the cAMP response element-binding protein (CREB),
      transcription factor in nucleus. Interestingly, the inhibition of ganglioside GM3
      synthesis by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol (D-PDMP)
      and GM3 synthase-siRNA blocked the CAPE-induced expression of the megakaryocytic
      markers and differentiation of K562 cells. Taken together, these results suggest
      that CAPE induces ganglioside GM3-mediated megakaryocytic differentiation of
      human chronic myelogenous cells. 

PMID- 24934092
TI  - What factors influence British medical students' career intentions?
AB  - AIM: The aim of this study was to identify factors that influence career choice
      in UK medical students. METHODS: Students at seven institutions were invited to
      rate how important various factors were on influencing their career choices and
      how interested they were in pursuing different specialties. The influence of
      interpersonal relationship networks on career choice was also evaluated. RESULTS:
      641 responses were collected. 44% (283) were male, 16% (105) were graduates and
      41% (263) were final-year students. For Dermatology (p = 0.009), Paediatrics (p =
      0.000), Radiology (p = 0.000), Emergency Medicine (p = 0.018) and Cardiothoracic
      Surgery (p = 0.000), there was a clear correlation between completing a clinical
      attachment and an interest in pursuing the specialty. Perceived characteristics
      of the speciality, individually and in clusters were considered important by
      specific subgroups of students, such as those interested in surgery. These
      students considered prestige (p = 0.0003), role models (p = 0.014), financial
      rewards after training (p = 0.0196) and technical challenge (p = 0.0011) as
      important factors. Demographics such as sex and age played a significant role in
      career choice. Interpersonal relationship networks do not have a significant
      influence on career intentions. CONCLUSIONS: This study shows that the career
      intentions of British medical students are influenced by their undergraduate
      experience and by the weight they place on different specialty-related factors.

PMID- 24934093
TI  - Medical models of teleoncology: current status and future directions.
AB  - Teleoncology has been adopted by many centers to provide cancer care closer to
      home for rural, remote, Indigenous and other disadvantaged people of our
      communities. A variety of medical models of teleoncology exist to provide various
      medical oncology services. While most centers use teleoncology to complement
      their face-to-face outreach services, some centers have replaced face-to-face
      with teleoncology models. Selection of patients and scheduling of clinics would
      depend on various factors including experience of the clinicians, complexity of
      treatment provided, capabilities and workforce of rural sites, and patient
      preferences. Many small studies reported high satisfaction rates of these models
      among patients and health professionals including Indigenous populations. One
      single center study reports that it is safe to supervise chemotherapy delivery
      remotely and many studies report cost savings to the health systems. Further
      studies on safety aspects of teleoncology are needed to further improve the
      current models. Future teleoncology models would need to include Web-based
      models, mobile technologies and remote chemotherapy supervision models so that
      patients from most rural towns could have at least some of their cancer care
      closer to home. 

PMID- 24934091
TI  - Association of multicellular behaviour and drug resistance in Salmonella enterica
      serovars isolated from animals and humans in Ethiopia.
AB  - AIMS: To determine the association between multicellular behaviour, integron
      status and antibiotic resistance among 87 Ethiopian Salmonella enterica isolates
      of animal and human origin. METHODS AND RESULTS: Isolates were characterized for
      their biofilm forming ability, antimicrobial susceptibility and the presence and
      characteristics of a class 1 integron and Salmonella genomic island 1 (SGI1). The
      majority of isolates grown at environmental temperatures (20 degrees C) exhibited
      robust biofilm formation (72.4%) and displayed RDAR colony morphology on Congo
      red agar plates. The presence of a class 1 integron correlated with the extent of
      drug resistance and ability to exhibit multicellular behaviour. CONCLUSIONS:
      Although cellulose production and RDAR morphology correlated with increased
      multicellular behaviour, neither was required for biofilm formation. Contrary to
      previous reports, colony morphology was generally consistent within a serovar. No
      integrons were detected in isolates deficient for multicellular behaviour,
      indicating a potential role of bacterial community formation in transfer of
      genetic elements among environmental isolates. SIGNIFICANCE AND IMPACT OF STUDY:
      Infection by Salm. enterica is a major public health problem worldwide. The
      dominance of multidrug resistance and multicellular behaviour in Salmonella
      isolates of Ethiopian origin highlights a need for integrated surveillance and
      further detailed phenotypic and molecular studies of isolates from this region.

PMID- 24934096
TI  - Synthesis and molecular structure of an abnormal carbene-gallium chloride
      complex.
AB  - Low temperature reaction of N-heterocyclic carbene : BEt3 with nBuLi (in THF)
      initially gives the C4-lithiated N-heterocyclic carbene : BEt3 complex (4), which
      isomerizes to the C2-lithiated abnormal N-heterocyclic carbene : BEt3 complex (2)
      in refluxing THF. While reaction of with GaCl3 gives a 4-functionalized N
      heterocyclic carbene : GaCl3 adduct (6), reaction of with GaCl3 affords the first
      abnormal carbene-gallium chloride complexes (5).

PMID- 24934094
TI  - A comparative study of two different clear aligner systems.
AB  - BACKGROUND: This study aims to compare the 'Nuvola(r)' system with
      'Fantasmino(r)' system, examine their material properties, and define the
      indications for use of the aligners. METHODS: Two groups of patients were
      selected and were respectively treated with Nuvola(r) aligner and Fantasmino(r)
      system. RESULTS: The goal of treatment has been achieved with the two systems.
      CONCLUSIONS: The two types of aligners have shown differences during the
      treatment. Fantasmino(r) system has elastic properties of high performance, but
      its size does not encourage compliance throughout the day. Nuvola(r) system
      determines good tooth movement and its size facilitates the patient's
      collaboration. In both aligner systems, difficulties were found in the correction
      of torque information and rotations.

PMID- 24934095
TI  - Barriers to and facilitators of the provision of a youth-friendly health services
      programme in rural South Africa.
AB  - BACKGROUND: Youth-friendly health services are a key strategy for improving young
      people's health. This is the first study investigating provision of the Youth
      Friendly Services programme in South Africa since the national Department of
      Health took over its management in 2006. In a rural area of South Africa, we
      aimed to describe the characteristics of the publicly-funded primary healthcare
      facilities, investigate the proportion of facilities that provided the Youth
      Friendly Services programme and examine healthcare workers' perceived barriers to
      and facilitators of the provision of youth-friendly health services. METHODS:
      Semi-structured interviews were conducted with nurses of all eight publicly
      funded primary healthcare facilities in Agincourt sub-district, Mpumalanga
      Province, South Africa. Thematic analysis of interview transcripts was conducted
      and data saturation was reached. RESULTS: Participants largely felt that the
      Youth Friendly Services programme was not implemented in their primary healthcare
      facilities, with the exception of one clinic. Barriers to provision reported by
      nurses were: lack of youth-friendly training among staff and lack of a dedicated
      space for young people. Four of the eight facilities did not appear to uphold the
      right of young people aged 12 years and older to access healthcare independently.
      Breaches in young people's confidentiality to parents were reported. CONCLUSIONS:
      Participants reported that provision of the Youth Friendly Services programme is
      limited in this sub-district, and below the Department of Health's target that
      70% of primary healthcare facilities should provide these services. Whilst a
      dedicated space for young people is unlikely to be feasible or necessary, all
      facilities have the potential to be youth-friendly in terms of staff attitudes
      and actions. Training and on-going support should be provided to facilitate this;
      the importance of such training is emphasised by staff. More than one member of
      staff per facility should be trained to allow for staff turnover. As one of a few
      countrywide, government-run youth-friendly clinic programmes in a low or middle
      income country, these results may be of interest to programme managers and policy
      makers in such settings.

PMID- 24934097
TI  - A simple technique for reinflating a Becker expander when tube breakage occurs
      during port removal.

PMID- 24934098
TI  - Nailbed reconstruction using dermal regeneration template.

PMID- 24934099
TI  - Comparison of ultrasonography-assisted closed reduction with conventional closed
      reduction for the treatment of acute nasal fractures.
AB  - Ultrasonography has often been reported to be a useful tool in cases of nasal
      fracture, not only for diagnosing such fractures but also for intraoperatively
      assessing surgical outcomes. In this study, we examined the utility of
      ultrasonography for intraoperatively assessing the results of surgery for acute
      nasal fractures. In the conventional group, the outcome of each fracture
      reduction procedure was intraoperatively confirmed by visual inspection and
      palpation. In the ultrasound group, intraoperative ultrasonography was used to
      assess the condition of the fracture before and after closed reduction. The
      outcomes of the reduction procedures and the reoperation rate were compared
      between the two groups. According to computed tomography-based evaluations, there
      were no significant differences in the outcomes of the reduction procedures
      between the two groups (p > 0.05). As for the reoperation rate, two patients
      (2.8%) in the conventional group underwent reoperations, but no patient (0%)
      required reoperations in the ultrasound group. However, the difference in the
      reoperation rate between the two groups was not significant (p > 0.05). These
      results indicate that visual inspection and palpation are as reliable as
      ultrasonography for intraoperatively assessing the outcomes of surgery for acute
      nasal fractures. Surgeons should not depend on ultrasonography alone, but rather
      should use it in addition to visual inspection and palpation. 

PMID- 24934100
TI  - External traction sutures to facilitate exposure in abdominoplasty: a novel
      technique.

PMID- 24934101
TI  - Growth, reaction and nanowire formation of Fe on the ZnS(1 0 0) surface.
AB  - The growth and reaction of Fe on a ZnS(1 0 0) substrate are studied in situ and
      with high lateral resolution using low energy electron microscopy (LEEM), micro
      low energy electron diffraction ( MULEED), x-ray photoemission electron
      microscopy (XPEEM), microprobe x-ray photoelectron spectroscopy ( MUXPS) and x
      ray magnetic circular dichroism PEEM (XMCDPEEM) for complementary structural,
      chemical, and magnetic characterization. Initially, a two-dimensional (Fe, Zn)S
      reaction layer forms with thickness that depends on growth temperature. Further
      growth results in the formation of a variety of three-dimensional crystals, most
      of them strongly elongated in the form of 'nanowires' of two distinct types,
      labeled as A and B. Type A nanowires are oriented near the ZnS[1 1 0] direction
      and are composed of Fe. Type B nanowires are oriented predominantly along
      directions a few degrees off the ZnS[0 0 1] direction and are identified as
      Greigite (Fe3S4). Both types of nanowires are magnetic with Curie temperatures
      above 450  degrees C. The understanding of the reactive growth mechanism in this
      system that is provided by these investigations may help to develop growth
      methods for other elemental and transition metal chalcogenide nanostructures on
      ZnS and possibly on other II-VI semiconductor surfaces. 

PMID- 24934102
TI  - A new room temperature gas sensor based on pigment-sensitized TiO2 thin film for
      amines determination.
AB  - A new room temperature gas sensor was fabricated with pigment-sensitized TiO2
      thin film as the sensing layer. Four natural pigments were extracted from spinach
      (Spinacia oleracea), red radish (Raphanus sativus L), winter jasmine (Jasminum
      nudiflorum), and black rice (Oryza sativa L. indica) by ethanol. Natural pigment
      sensitized TiO2 sensor was prepared by immersing porous TiO2 films in an ethanol
      solution containing a natural pigment for 24h. The hybrid organic-inorganic
      formed films here were firstly exposed to atmospheres containing methylamine
      vapours with concentrations over the range 2-10 ppm at room temperature. The
      films sensitized by the pigments from black-rice showed an excellent gas
      sensitivity to methylamine among the four natural pigments sensitized films due
      to the anthocyanins. The relative change resistance, S, of the films increased
      almost linearly with increasing concentrations of methylamine (r=0.931). At last,
      the black rice pigment sensitized TiO2 thin film was used to determine the
      biogenic amines generated by pork during storage. The developed films had good
      sensitivity to analogous gases such as putrscine, and cadaverine that will
      increase during storage.

PMID- 24934103
TI  - Quality evaluation of different preparations of dry extracts of birch (Betula
      pendula Roth) leaves.
AB  - Qualitatively prepared dry extracts are advantaged over conventional fluid
      extracts. Extracts of Betula pendula Roth leaves possess mild diuretic effects
      and anti-inflammatory activity. In this work, the spray-drying and lyophilisation
      processes were evaluated for producing dry extracts of birch leaves. The purpose
      was to identify the best drying method that provides the highest content of
      phenolic compounds and possesses greatest antioxidant activity. Predominant
      compounds hyperoside and chlorogenic acid were chosen as markers for the
      quantitative control of phenolic compounds. Their determined amounts in
      hydroalcoholic birch leaf extract were 15.85 and 8.77 mg/g of dry residue,
      respectively. Insignificant differences were determined in spray- and freeze
      dried extracts. In the antioxidant profile, hyperoside (28.9 MUmol TE/g dw) and
      chlorogenic acid (22.8 MUmol TE/g dw) possessed strongest ferric-reducing
      activity. Also, no significant differences of antioxidant activity were
      determined in the spray- and freeze-dried extracts.

PMID- 24934105
TI  - Subcentimeter lung nodules stable for 2 years at LDCT: long-term follow-up using
      volumetry.
AB  - BACKGROUND AND OBJECTIVE: Subcentimeter nodules without change in size during
      long-term follow-up period (for minimum 2 years) are assumed as benign lesions.
      However, the 2-year stability rule has not been fully verified so far and is
      still questionable. Thus, we aimed to retrospectively investigate long-term
      follow-up results for 2-year stable subcentimeter nodules at screening low-dose
      computed tomography (LDCT). METHODS: A total of 635 subjects having had follow-up
      LDCTs for the initial 2-year screening period and additional 3 years thereafter
      and having had non-calcified subcentimeter nodules were included. By using
      computed tomography (CT) nodule volumetry software, we measured interval changes
      in nodule volume. RESULTS: A total of 1107 subcentimeter nodules (1037 solid, 70
      ground-glass opacity nodules (GGNs)) were detected at baseline CT. Of 1037 solid
      nodules, 1032 showed no growth during the initial 2-year and 5-year follow-up
      period. Fifty-nine GGNs were stable for initial 2 years, but two (3.4%) were
      later proved as adenocarcinomas. Among five solid nodules that showed growth
      during the initial 2-year follow-up period, one (20%) proved to be an
      adenocarcinoma, whereas four (36.4%) of 11 GGNs that demonstrated growth were
      diagnosed as lung cancers. CONCLUSIONS: All solid subcentimeter nodules having
      initial 2-year stability at screening LDCT can be considered benign because none
      shows growth at further follow-up CT. On the other hand, subcentimeter GGNs have
      more chance of growth than solid nodules and need further follow-up CT for more
      than 2 years.

PMID- 24934104
TI  - Explore on the effect of ATF6 on cell growth and apoptosis in cartilage
      development.
AB  - We previously report that BMP2 mediates mild ER stress-activated ATF6 and
      directly regulates XBP1S splicing in the course of chondrogenesis. The mammalian
      unfolded protein response (UPR) protects the cell against the stress of misfolded
      proteins in the endoplasmic reticulum (ER). Failure to adapt to ER stress causes
      the UPR to trigger apoptosis. The transcription factor activating transcription
      factor 6 (ATF6), a key regulator of the UPR, is known to be important for ER
      stress-mediated apoptosis and cell growth, but the molecular mechanism underlying
      these processes remains unexplored. In this study, we demonstrate that ATF6 is
      differentially expressed during BMP2-stimulated chondrocyte differentiation and
      exhibits prominent expression in growth plate chondrocytes. ATF6 can enhance the
      level of IRE1a-spliced XBP1S protein in chondrogenesis. IRE1a and ATF6 can
      synergistically regulate endogenous XBP1S gene expression in chondrogenesis.
      Furthermore, overexpression ATF6 inhibited, while ATF6-knockdown enhanced, the
      cell proliferation in chondrocyte development with G1 phase arresting, S phase
      reducing and G2-M phase delaying. Besides, Ad-ATF6 can activate, whereas
      knockdown ATF6 by an siRNA-silencing approach inhibited, ER stress-mediated
      apoptosis in chondrogenesis induced by BMP2, as assayed by cleaved caspase3,
      CHOP, p-JNK expression in the course of chondrocyte differentiation. On the other
      hand, FCM, TUNEL assay and immunohistochemistry analysis also proved this result
      in vitro and in vivo. It was demonstrated that Ad-ATF6 activation of the ER
      stress-specific caspase cascade in developing chondrocyte tissue. Collectively,
      these findings reveal a novel critical role of ATF6 in regulating ER stress
      mediated apoptosis in chondrocyte differentiation and the molecular mechanisms
      involved. 

PMID- 24934106
TI  - Co-development of manner and path concepts in language, action, and eye-gaze
      behavior.
AB  - In order for artificial intelligent systems to interact naturally with human
      users, they need to be able to learn from human instructions when actions should
      be imitated. Human tutoring will typically consist of action demonstrations
      accompanied by speech. In the following, the characteristics of human tutoring
      during action demonstration will be examined. A special focus will be put on the
      distinction between two kinds of motion events: path-oriented actions and manner
      oriented actions. Such a distinction is inspired by the literature pertaining to
      cognitive linguistics, which indicates that the human conceptual system can
      distinguish these two distinct types of motion. These two kinds of actions are
      described in language by more path-oriented or more manner-oriented utterances.
      In path-oriented utterances, the source, trajectory, or goal is emphasized,
      whereas in manner-oriented utterances the medium, velocity, or means of motion
      are highlighted. We examined a video corpus of adult-child interactions comprised
      of three age groups of children-pre-lexical, early lexical, and lexical-and two
      different tasks, one emphasizing manner more strongly and one emphasizing path
      more strongly. We analyzed the language and motion of the caregiver and the
      gazing behavior of the child to highlight the differences between the tutoring
      and the acquisition of the manner and path concepts. The results suggest that age
      is an important factor in the development of these action categories. The
      analysis of this corpus has also been exploited to develop an intelligent robotic
      behavior-the tutoring spotter system-able to emulate children's behaviors in a
      tutoring situation, with the aim of evoking in human subjects a natural and
      effective behavior in teaching to a robot. The findings related to the
      development of manner and path concepts have been used to implement new effective
      feedback strategies in the tutoring spotter system, which should provide
      improvements in human-robot interaction. 

PMID- 24934107
TI  - Continuous intravenous beta-lactam antibiotics in cystic fibrosis patients with
      severe drug hypersensitivity.

PMID- 24934108
TI  - Metal hypersensitivity in total joint arthroplasty.
AB  - OBJECTIVE: To review the clinical manifestations, testing methods, and treatment
      options for hypersensitivity reactions to total joint arthroplasty procedures.
      DATA SOURCES: Studies were identified using MEDLINE and reference lists of key
      articles. STUDY SELECTIONS: Randomized controlled trials were selected when
      available. Systematic reviews and meta-analyses of peer-reviewed literature were
      included, as were case series and observational studies of clinical interest.
      RESULTS: Total joint arthroplasty procedures are increasing, as are the
      hypersensitivity reactions to these implants. Evidence is not conclusive as to
      whether metal joint implants increase metal sensitivity or whether metal
      sensitivity leads to prosthesis failure. Currently, patch testing is still the
      most widely used method for determining metal hypersensitivity; however, there
      are no standardized commercial panels specific for total joint replacements
      available currently. In vitro testing has shown comparable results in some
      studies, but its use in the clinical setting may be limited by the cost and need
      for specialized laboratories. Hypersensitivity testing is generally recommended
      before surgery for patients with a reported history of metal sensitivity. In
      cases of metal hypersensitivity-related joint failure, surgical revision
      ultimately may be required. Knowledge about joint replacement hypersensitivity
      reactions becomes vital because the approach to the evaluation depends on
      appropriate testing to guide recommendations for future arthroplasty procedures.
      CONCLUSION: Evaluation of hypersensitivity reactions after total joint
      arthroplasty requires a systematic approach, including a careful history,
      targeted evaluation with skin testing, and in vitro studies.

PMID- 24934109
TI  - Asthma and toxocariasis.
AB  - BACKGROUND: Asthma is the most common chronic disease in children and a major
      public health problem in adults. A relation between asthma and toxocariasis has
      been hypothesized. OBJECTIVE: To evaluate the strength of association between
      asthma and Toxocara species seropositivity by conducting a systematic review and
      a meta-analysis of available data. METHODS: PubMed, EMBASE, Web of Science, and
      the reference lists of all relevant articles and books were screened until
      October 2013. Two authors independently assessed eligibility and study quality
      and extracted data. A common odds ratio was estimated using a random-effects meta
      analysis model of aggregated published data. RESULTS: Ten studies met the
      inclusion criteria, for a total of 1,530 participants (723 cases and 807
      controls). This meta-analysis found a significantly higher prevalence of Toxocara
      canis infection in patients with asthma than in controls (odds ratio 3.36, 95%
      confidence interval 1.76-6.42, P < .001). Similar results were found when meta
      analysis was restricted to the studies considering only children or adults.
      CONCLUSION: The results support the existence of a positive association between
      asthma and Toxocara species seropositivity.

PMID- 24934110
TI  - [Hepatic artery infusional and systemic chemotherapy for patients with
      unresectable hepatic metastases from colorectal cancer: a phase II trial].

PMID- 24934111
TI  - [Outcome of patients with esophageal perforations: results of a multicenter
      study].

PMID- 24934112
TI  - On board with the Choosing Wisely campaign.

PMID- 24934113
TI  - The motor neuron response to SMN1 deficiency in spinal muscular atrophy.

PMID- 24934115
TI  - Phosphoglycerate kinase deficiency due to a novel mutation (c. 1180A>G)
      manifesting as chronic hemolytic anemia in a Japanese boy.
AB  - Phosphoglycerate kinase (PGK) deficiency, a rare X-linked inherited disorder,
      manifests as various combinations of hemolytic anemia, neurological dysfunction,
      and myopathy. We report a Japanese boy with PGK deficiency presenting as chronic
      hemolytic anemia. The diagnosis of PGK1 deficiency was made at 11 months of age
      on the basis of low PGK enzyme activity (36.7 IU/g Hb; normal, 264-326 IU/g Hb)
      and the identification through PGK1 gene sequencing of a novel missense mutation:
      c. 1180A>G at exon 10. The mutation, which has been designated PGK-Aoto, results
      in a Thr394Ala amino-acid substitution at beta-strand L. Because beta-strand L
      plays an important role in the function of the hinge connecting the two domains
      of PGK, the Thr394Ala substitution may perturb this motion. At 3 years of age the
      patient has transfusion-dependent hemolytic anemia but no evidence of
      neuromuscular disease or developmental delay. Long-term follow-up will be needed
      to identify possible future clinical manifestations. 

PMID- 24934116
TI  - A possible familial lymphoproliferative disorder in two male siblings of children
      with recurrent wheezing and lung infections since infancy.
AB  - Malignancies that result in wheezing in infants are very uncommon. Given its
      rarity in children, the diagnosis is challenging, and in the absence of a high
      index of suspicion, delayed diagnosis is not uncommon. Here we report two male
      siblings of children who presented with recurrent wheezing and recurrent lung
      infections since infancy. Both children showed no laboratory evidence of
      immunodeficiency. Lymphocytic interstitial pneumonia or hypersensitivity
      pneumonitis was histologically suspected in lung biopsy specimens from the older
      brother. He subsequently developed Epstein-Barr virus (EBV)-associated
      hemophagocytic lymphohistiocytosis and died. Based on the family history, we
      screened mutations among PRF1, Munc13-4, STX11, SH2D1A, and XIAP genes for the
      younger brother, but did not identify any mutations. He also underwent lung
      biopsy, which showed interstitial infiltration of lymphoid cells. In situ
      hybridization for EBV-encoded RNA showed a positive nuclear signal in the
      lymphoid cells. The presence of clonal B-cell proliferations was detected by
      clonally rearranged immunoglobulin studies. Lymphomatoid granulomatosis grade 3
      was finally diagnosed. The progression of disease was rapid, and the patient
      died, despite rituximab therapy. The similar clinical manifestations in two male
      siblings suggest the possibility that a previously undescribed genetic defect
      contributed to these familial lymphoproliferative malignancies. 

PMID- 24934117
TI  - Immediate therapeutic efficacy of low-density lipoprotein apheresis for drug
      resistant nephrotic syndrome: evidence from the short-term results from the
      POLARIS Study.
AB  - BACKGROUND: Hyperlipidemia is not merely a complication but a major exacerbating
      factor in longstanding nephrotic syndrome (NS). Low-density lipoprotein apheresis
      (LDL-A) has been reported to ameliorate dyslipidemia and induce rapid remission
      of NS. Several clinical studies have suggested the therapeutic efficacy of LDL-A,
      but the level of clinical evidence is insufficient. Therefore, a multicenter
      prospective study, POLARIS (Prospective Observational Survey on the Long-Term
      Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was initiated in
      Japan. METHOD: Patients with drug-resistant NS were prospectively recruited into
      the study and treated with LDL-A in facilities that were registered in advance.
      In the POLARIS study design, the clinical data are to be followed up for 2 years.
      In the current study, we aimed at evaluating the short-term efficacy based on the
      treatment outcome of LDL-A immediately after completion of treatment. RESULTS:
      Along with rapid improvement of hyperlipidemia, LDL-A significantly improved
      proteinuria and hypoproteinemia after treatment. More than half of the patients
      showed remission of NS based on the urinary protein level at the completion of
      LDL-A. The duration of NS before the start of treatment was significantly shorter
      in patients who responded to LDL-A. CONCLUSIONS: An analysis of patients
      registered in the POLARIS study indicated that LDL-A has short-term efficacy for
      drug-resistant NS. Rapid relief of dyslipidemia by LDL-A may provide early
      remission in about half of the NS patients who are resistant to conventional
      medication. Completion of the POLARIS study may reveal additional long-term
      effects of LDL-A in these patients.

PMID- 24934118
TI  - Differential recombination dynamics within the MHC of macaque species.
AB  - A panel of 15 carefully selected microsatellites (short tandem repeats, STRs) has
      allowed us to study segregation and haplotype stability in various macaque
      species. The STRs span the major histocompatibility complex (MHC) region and map
      in more detail from the centromeric part of the Mhc-A to the DR region. Two large
      panels of Indian rhesus and Indonesian/Indochinese cynomolgus macaques have been
      subjected to pedigree analysis, allowing the definition of 161 and 36 different
      haplotypes and the physical mapping of 10 and 5 recombination sites,
      respectively. Although most recombination sites within the studied section of the
      Indian rhesus monkey MHC are situated between the Mhc-A and Mhc-B regions, the
      resulting recombination rate for this genomic segment is low and similar to that
      in humans. In contrast, in Indonesian/Indochinese macaques, two recombination
      sites, which appear to be absent in rhesus macaques, map between the class III
      and II regions. As a result, the mean recombination frequency of the core MHC,
      Mhc-A to class II, is higher in Indonesian/Indochinese cynomolgus than in Indian
      rhesus macaques, but as such is comparable to that in humans. The present
      communication demonstrates that the dynamics of recombination 'hot/cold spots' in
      the MHC, as well as their frequencies, may differ substantially between highly
      related macaque species. 

PMID- 24934119
TI  - Characterization of a polymorphic IGLV gene in pigs (Sus scrofa).
AB  - Swine, unlike other artiodactyls, but similar to humans, utilize both lambda and
      kappa light chain isotypes almost equally in the generation of their antibody
      repertoire. The porcine antibody light chain loci have previously been
      characterized in a single Duroc sow in which was seen extensive allelic variation
      between light chain genes on homologous chromosomes. However, the extent of
      variation between individuals is completely unknown. Using deep sequencing of
      cDNA-derived amplicons from five pigs, we report the identification and
      characterization of an IGLV gene that is functional and highly expressed in some
      animals, yet completely absent in others. Our findings provide a possible
      rationale for the known individual-to-individual variation in antibody responses
      to vaccination, infectious challenge, and subsequent disease outcome. 

PMID- 24934120
TI  - A rare precursor of gastric tumor.
AB  - Gastritis cystica profunda (GCP) is a rare tumor precursor which occurs more
      commonly in patients who have undergone previous gastric surgery. The non
      specific symptoms and radiographic appearance of this tumor mimic those of other
      hyperproliferative conditions, making diagnosis difficult. This is a pre
      malignant condition and may lead on to carcinoma of the stomach. Here we report a
      57-year-old female with no previous gastric surgeries, who presented to us with
      epigastric abdominal pain. Her work-up included an upper endoscopy, which
      revealed fundic polyps. Her fundal biopsies were consistent with GCP. 

PMID- 24934123
TI  - Surgical treatment of equine colic - a retrospective study of 297 surgeries in
      Norway 2005-2011.
AB  - BACKGROUND: Colic, defined as pain originating from the abdomen, is a common
      condition in horses. Most of the cases resolve spontaneously or after medical
      treatment, but a few require surgical treatment. Surgical treatment of colic in
      horses is resource-demanding and expensive, and information on prognosis is
      therefore important for both owners and surgeons. In the present study, surgical
      cases in two equine hospitals in Norway between 2005 and 2011 were reviewed. The
      aim of the study was to describe associations between prognostic indicators,
      diagnoses and short term survival by use of random effects logistic regression.
      RESULTS: In the present study, 162 out of 297 (54.5%) surgeries resulted in the
      horse being discharged from the hospital. Excluding cases euthanized during
      surgery, the overall short-term survival was 74.0% (162 out of 219 surgeries).
      Seventy-eight (26.3%) of the horses were euthanized during surgery, due to grave
      or poor prognosis. In univariable analyses, duration of colic signs, heart rate,
      capillary refill time, mucosal membrane appearance, intestinal sounds, affected
      gastrointestinal segment, hematocrit, intestinal resection, hospital and surgeon
      board-certification had P-value <0.20 and were assessed in multivariable
      analyses. Respiration rate, rectal temperature and lactate in blood also had
      univariable P <0.20, but were left out from multivariable analyses due to too
      high levels of missing values. A random effect of primary surgeon was included
      and breed, sex and age were tested in multivariable analyses as possible
      confounders; and hospital was included to control for hospital routine
      differences. In the final multivariable model the variables mucosal membrane
      appearance, affected gastrointestinal segment and surgeon board-certification
      significantly influenced survival. The random surgeon effect was not significant.
      CONCLUSIONS: The present study showed that prognostic parameters and diagnoses of
      surgical treatment of horses with colic in Norway are in accordance with reports
      from other parts of the world. The significant effect of board-certification of
      surgeon is not reported in previous studies. The general short-term survival rate
      was somewhat lower than reported in other studies, partly due to more horses
      being euthanized intraoperatively in the present study. This might be because of
      economical or animal welfare reasons.

PMID- 24934124
TI  - Rebuttal to Riek LM, Ludewig PM, Nawoczenski DA. How "healthy" is circuit
      resistance training following paraplegia? Kinematic analysis associated with
      shoulder mechanical impingement risk. J Rehabil Res Dev. 2013:50(6):861-74.
      http://dx.doi.org/10.1682/JRRD.2012.06.0112.

PMID- 24934125
TI  - Response.

PMID- 24934126
TI  - Training model for promoting translation from research to clinical settings:
      University of Alabama at Birmingham training for constraint-induced movement
      therapy.

PMID- 24934127
TI  - Continuous practice quality improvement initiative for communication of critical
      findings in neuroradiology.
AB  - The authors examined faculty's compliance with a hospital-approved neuroradiology
      critical findings (CFs) policy, which requires urgent verbal communication with
      the clinical team when 17 specific critical pathologies are identified. During
      June 2011 to July 2013, 50 random neuroradiology reports were sampled monthly for
      the presence of CFs and appropriate action. Faculty were provided ongoing
      feedback, and at the end of 2 years, the medical records for cases with
      noncommunicated CFs were reviewed to identify potential adverse outcomes. Of the
      1200 reviewed reports, 195 (16.3%) had and 1005 (83.8%) did not have a CF. A
      total of 176 of 195 (90.3%) cases with CFs were communicated, and compliance
      increased from 77.4% to 85.6% (P = .027) since the monthly sampling was
      instituted; 1 of 19 (5.3%) noncommunicated CFs resulted in a potential adverse
      event. The ongoing monthly feedback resulted in improved faculty compliance with
      the CF policy. However, a small number of cases with CFs are still not being
      communicated. 

PMID- 24934128
TI  - Mutations in Ovis aries TMEM154 are associated with lower small ruminant
      lentivirus proviral concentration in one sheep flock.
AB  - Small ruminant lentivirus (SRLV), also called ovine progressive pneumonia virus
      or maedi-visna, is present in 24% of US sheep. Like human immunodeficiency virus,
      SRLV is a macrophage-tropic lentivirus that causes lifelong infection. The
      production impacts from SRLV are due to a range of disease symptoms, including
      pneumonia, arthritis, mastitis, body condition wasting and encephalitis. There is
      no cure and no effective vaccine for preventing SRLV infection. However, breed
      differences in prevalence and proviral concentration indicate a genetic basis for
      susceptibility to SRLV. Animals with high blood proviral concentration show
      increased tissue lesion severity, so proviral concentration represents a live
      animal test for control post-infection in terms of proviral replication and
      disease severity. Recently, it was found that sheep with two copies of TMEM154
      haplotype 1 (encoding lysine at position 35) had lower odds of SRLV infection. In
      this study, we examined the relationship between SRLV control post-infection and
      variants in two genes, TMEM154 and CCR5, in four flocks containing 1403 SRLV
      positive sheep. We found two copies of TMEM154 haplotype 1 were associated with
      lower SRLV proviral concentration in one flock (P < 0.02). This identified the
      same favorable diplotype for SRLV control post-infection as for odds of
      infection. However, frequencies of haplotypes 2 and 3 were too low in the other
      three flocks to test. The CCR5 promoter deletion did not have consistent
      association with SRLV proviral concentration. Future work in flocks with more
      balanced allele frequencies is needed to confirm or refute TMEM154 association
      with control of SRLV post-infection.

PMID- 24934130
TI  - Influence of urban form on landscape pattern and connectivity in metropolitan
      regions: a comparative case study of Phoenix, AZ, USA, and Izmir, Turkey.
AB  - Although ecological connectivity conservation in urban areas has recently been
      recognized as an important issue, less is known about its relationship to urban
      form and landscape pattern. This study investigates how urban morphology
      influences regional ecosystem pattern and landscape connectivity. Two
      metropolitan landscapes, Phoenix, AZ, USA, and Izmir, Turkey, were compared, both
      of which are fast-growing regions in their national context. A wide range of
      variables were considered for identifying natural and urban properties. The
      natural characteristics include typology of urban ecosystems, urban to natural
      cover ratio, dominant habitat type, urban biodiversity, landscape context, and
      connectivity conservation efforts. Urban parameters examine urban form, urban
      extent, urban cover proportion, growth rate, populations, urban gradient, major
      drivers of urbanization, urban density, and mode/approach of urban development.
      Twelve landscape metrics were measured and compared across the natural patches.
      Results show that there is little difference in landscape connectivity in the
      rural zones of Phoenix and Izmir, although Phoenix has slightly higher
      connectivity values. The connectivity variance in urbanized areas, however, is
      significantly dependent on the region. For example, Phoenix urban zones have
      substantially lower connectivity than either urban or suburban zones in Izmir.
      Findings demonstrate that small and compact urban settlements with more dense
      populations are more likely to conserve landscape connectivity compared to
      multiple-concentric but amalgamated urban form spreading all over the landscape
      (aka urban sprawl). 

PMID- 24934129
TI  - Immunoproteasome in animal models of Duchenne muscular dystrophy.
AB  - Increased proteasome activity has been implicated in the atrophy and
      deterioration associated with dystrophic muscles of Duchenne muscular dystrophy
      (DMD). While proteasome inhibitors show promise in the attenuation of muscle
      degeneration, proteasome inhibition-induced toxicity was a major drawback of this
      therapeutic strategy. Inhibitors that selectively target the proteasome subtype
      that is responsible for the loss in muscle mass and quality would reduce side
      effects and be less toxic. This study examined proteasome activity and subtype
      populations, along with muscle function, morphology and damage in wild-type (WT)
      mice and two murine models of DMD, dystrophin-deficient (MDX) and dystrophin- and
      utrophin-double-knockout (DKO) mice. We found that immunoproteasome content was
      increased in dystrophic muscles while the total proteasome content was unchanged
      among the three genotypes of mice. Proteasome proteolytic activity was elevated
      in dystrophic muscles, especially in DKO mice. These mice also exhibited more
      severe muscle atrophy than either WT or MDX mice. Muscle damage and regeneration,
      characterized by the activity of muscle creatine kinase in the blood and the
      percentage of central nuclei were equally increased in dystrophic mice.
      Accordingly, the overall muscle function was similarly reduced in both dystrophic
      mice compared with WT. These data demonstrated that there was transformation of
      standard proteasomes to immunoproteasomes in dystrophic muscles. In addition, DKO
      that showed greatest increase in proteasome activities also demonstrated more
      severe atrophy compared with MDX and WT. These results suggest a putative role
      for the immunoproteasome in muscle deterioration associated with DMD and provide
      a potential target for therapeutic intervention.

PMID- 24934132
TI  - Forelimb anatomy and the discrimination of the predatory behavior of carnivorous
      mammals: the thylacine as a case study.
AB  - Carnivorous mammals use their forelimbs in different ways to capture their prey.
      Most terrestrial carnivores have some cursorial (running) adaptations, but ambush
      predators retain considerable flexibility in their forelimb movement, important
      for grappling with their prey. In contrast, predators that rely on pursuit to run
      down their prey have sacrificed some of this flexibility for locomotor
      efficiency, in the greater restriction of the forelimb motion to the parasagittal
      plane. In this article, we measured aspects of the forelimb anatomy (44 linear
      measurements) in 36 species of carnivorous mammals of known predatory behavior,
      and used multivariate analyses to investigate how well the forelimb anatomy
      reflects the predatory mode (ambush, pursuit, or pounce-pursuit). A prime
      intention of this study was to establish morphological correlates of behavior
      that could then be applied to fossil mammals: for this purpose, five individuals
      of the recently extinct thylacine (Thylacinus cynocephalus) were also included as
      unknowns. We show that the three different types of predators can be
      distinguished by their morphology, both in analyses where all the forelimb bones
      are included together, and in the separate analyses of each bone individually. Of
      particular interest is the ability to distinguish between the two types of more
      cursorial predators, pursuit and pounce-pursuit, which have previously been
      considered as primarily size-based categories. Despite a prior consideration of
      the thylacine as a "pounce-pursuit" or an "ambush" type of predator, the
      thylacines did not consistently cluster with any type of predatory carnivores in
      our analyses. Rather, the thylacines appeared to be more generalized in their
      morphology than any of the extant carnivores. The absence of a large diversity of
      large carnivorous mammals in Australia, past and present, may explain the
      thylacine's generalized morphology.

PMID- 24934131
TI  - Reproductive health indicators of fishes from Pennsylvania watersheds:
      association with chemicals of emerging concern.
AB  - Fishes were collected at 16 sites within the three major river drainages
      (Delaware, Susquehanna, and Ohio) of Pennsylvania. Three species were evaluated
      for biomarkers of estrogenic/antiandrogenic exposure, including plasma
      vitellogenin and testicular oocytes in male fishes. Smallmouth bass Micropterus
      dolomieu, white sucker Catostomus commersonii, and redhorse sucker Moxostoma
      species were collected in the summer, a period of low flow and low reproductive
      activity. Smallmouth bass were the only species in which testicular oocytes were
      observed; however, measurable concentrations of plasma vitellogenin were found in
      male bass and white sucker. The percentage of male bass with testicular oocytes
      ranged from 10 to 100%, with the highest prevalence and severity in bass
      collected in the Susquehanna drainage. The percentage of males with plasma
      vitellogenin ranged from 0 to 100% in both bass and sucker. Biological findings
      were compared with chemical analyses of discrete water samples collected at the
      time of fish collections. Estrone concentrations correlated with testicular
      oocytes prevalence and severity and with the percentage of male bass with
      vitellogenin. No correlations were noted with the percentage of male sucker with
      vitellogenin and water chemical concentrations. The prevalence and severity of
      testicular oocytes in bass also correlated with the percent of agricultural land
      use in the watershed above a site. Two sites within the Susquehanna drainage and
      one in the Delaware were immediately downstream of wastewater treatment plants to
      compare results with upstream fish. The percentage of male bass with testicular
      oocytes was not consistently higher downstream; however, severity did tend to
      increase downstream.

PMID- 24934134
TI  - Adverse drug events in patients admitted to an emergency department: an analysis
      of direct costs.
AB  - PURPOSE: Several economic evaluations of adverse drug events (ADEs) exist, but
      the underlying methodology has not been standardized so far. The aim of the study
      was to combine prospective, intensive pharmacovigilance methods, and standardized
      accounting data to calculate direct costs of community-acquired ADEs (caADEs)
      contributing to emergency department (ED) admission and subsequent
      hospitalization. METHODS: A prospective observational study with three phases
      extending over 2 years was implemented in a 749 bed tertiary care hospital with
      an annual ED census of approximately 45 000 patients. The patient records of all
      adult non-trauma ED admissions were systematically analyzed by a team of
      emergency physicians, clinical pharmacologists, and pharmacists for potential
      ADE. Associated diagnosis related group costs were extracted from standardized
      accounting data. RESULTS: Of 2262 patients attending the ED during the study
      periods, the hospitalization of 366 patients (16.2%) was related to one or more
      caADEs of which 97.5% were considered predictable and 62.0% were classified as
      preventable. The mean caADE-related diagnosis related group costs were ?2743 (95%
      bias-corrected and accelerated CI: ?2498 to ?3018). Extrapolated to a national
      scale, this corresponds to caADE-related costs of ?2.245bn for the German health
      insurance funds, annually. Costs of ?1.310bn could be attributed to events
      classified as predictable and preventable. CONCLUSIONS: In an ED, caADEs are
      frequent, and a significant proportion of these events and their related costs
      appear to be predictable and preventable. The ED as a first-line provider for ADE
      cases appears to be an appropriate environment to implement strategic and
      operative improvements for enhanced patient safety.

PMID- 24934135
TI  - Epilepsy: Chemical-genetic seizure silencing--unlocking the potential.

PMID- 24934133
TI  - The own-age bias in face memory is unrelated to differences in attention-
      evidence from event-related potentials.
AB  - Participants are more accurate at remembering faces from their own relative to a
      different age group (the own-age bias, or OAB). A recent socio-cognitive account
      has suggested that differential allocation of attention to old versus young faces
      underlies this phenomenon. Critically, empirical evidence for a direct
      relationship between attention to own- versus other-age faces and the OAB in
      memory is lacking. To fill this gap, we tested the roles of attention in three
      different experimental paradigms, and additionally analyzed event-related brain
      potentials (ERPs). In Experiment 1, we compared the learning of old and young
      faces during focused versus divided attention, but revealed similar OABs in
      subsequent memory for both attention conditions. Similarly, manipulating
      attention during learning did not differentially affect the ERPs elicited by
      young versus old faces. In Experiment 2, we examined the repetition effects from
      task-irrelevant old and young faces presented under varying attentional loads on
      the N250r ERP component as an index of face recognition. Independent of load, the
      N250r effects were comparable for both age categories. Finally, in Experiment 3
      we measured the N2pc as an index of attentional selection of old versus young
      target faces in a visual search task. The N2pc was not significantly different
      for the young versus the old target search conditions, suggesting similar
      orientations of attention to either face age group. Overall, we propose that the
      OAB in memory is largely unrelated to early attentional processes. Our findings
      therefore contrast with the predictions from socio-cognitive accounts on own
      group biases in recognition memory, and are more easily reconciled with expertise
      based models. 

PMID- 24934136
TI  - Stroke: Comparable care, worse outcomes for women with stroke.

PMID- 24934137
TI  - Cerebral aneurysms: Genetic risk factors are associated with the site of
      intracranial aneurysm development.

PMID- 24934138
TI  - Epilepsy: Electrophysiology elucidates epileptiform activity.

PMID- 24934139
TI  - Disorders of consciousness: Diagnostic accuracy of brain imaging in the
      vegetative state.

PMID- 24934141
TI  - Neurosurgery: Directional electrodes widen the therapeutic window for deep brain
      stimulation in movement disorders.

PMID- 24934140
TI  - Neurodevelopmental disorders: Elevated fetal sex steroids might confer risk for
      autism.

PMID- 24934142
TI  - SOS score: an optimized score to screen acute stroke patients for obstructive
      sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is frequent in acute stroke patients,
      and has been associated with higher mortality and worse prognosis.
      Polysomnography (PSG) is the gold standard diagnostic method for OSA, but it is
      impracticable as a routine for all acute stroke patients. We evaluated the
      accuracy of two OSA screening tools, the Berlin Questionnaire (BQ), and the
      Epworth Sleepiness Scale (ESS) when administered to relatives of acute stroke
      patients; we also compared these tools against a combined screening score (SOS
      score). METHODS: Ischemic stroke patients were submitted to a full PSG at the
      first night after onset of symptoms. OSA severity was measured by apnea-hypopnea
      index (AHI). BQ and ESS were administered to relatives of stroke patients before
      the PSG and compared to SOS score for accuracy and C-statistics. RESULTS: We
      prospectively studied 39 patients. OSA (AHI >=10/h) was present in 76.9%. The SOS
      score [area under the curve (AUC): 0.812; P = 0.005] and ESS (AUC: 0.789; P =
      0.009) had good predictive value for OSA. The SOS score was the only tool with
      significant predictive value (AUC: 0.686; P = 0.048) for severe OSA (AHI >=30/h),
      when compared to ESS (P = 0.119) and BQ (P = 0.191). The threshold of SOS <=10
      showed high sensitivity (90%) and negative predictive value (96.2%) for OSA; SOS
      >=20 showed high specificity (100%) and positive predictive value (92.5%) for
      severe OSA. CONCLUSIONS: The SOS score administered to relatives of stroke
      patients is a useful tool to screen for OSA and may decrease the need for PSG in
      acute stroke setting.

PMID- 24934143
TI  - Embedded 3D printing of strain sensors within highly stretchable elastomers.
AB  - A new method, embedded-3D printing (e-3DP), is reported for fabricating strain
      sensors within highly conformal and extensible elastomeric matrices. e-3DP allows
      soft sensors to be created in nearly arbitrary planar and 3D motifs in a highly
      programmable and seamless manner. Several embodiments are demonstrated and sensor
      performance is characterized. 

PMID- 24934145
TI  - Patient encounters of a difficult kind.

PMID- 24934144
TI  - Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile
      and long-term effect of immunotherapy.
AB  - IMPORTANCE: Current clinical and immunologic knowledge on cerebellar ataxia (CA)
      with glutamic acid decarboxylase 65 antibodies (GAD65-Abs) is based on case
      reports and small series with short-term follow-up data. OBJECTIVE: To report the
      symptoms, additional antibodies, prognostic factors, and long-term outcomes in a
      cohort of patients with CA and GAD65-Abs. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cohort study and laboratory investigations at a center for
      autoimmune neurologic disorders among 34 patients with CA and GAD65-Abs,
      including 25 with long-term follow-up data (median, 5.4 years; interquartile
      range, 3.1-10.3 years). MAIN OUTCOMES AND MEASURES: Analysis of
      clinicoimmunologic features and predictors of response to immunotherapy.
      Immunochemistry on rat brain, cultured neurons, and human embryonic kidney cells
      expressing GAD65, GAD67, alpha1-subunit of the glycine receptor, and a repertoire
      of known cell surface autoantigens were used to identify additional antibodies.
      Twenty-eight patients with stiff person syndrome and GAD65-Abs served as
      controls. RESULTS: The median age of patients was 58 years (range, 33-80 years);
      28 of 34 patients (82%) were women. Nine patients (26%) reported episodes of
      brainstem and cerebellar dysfunction or persistent vertigo several months before
      developing CA. The clinical presentation was subacute during a period of weeks in
      13 patients (38%). Nine patients (26%) had coexisting stiff person syndrome
      symptoms. Systemic organ-specific autoimmunities (type 1 diabetes mellitus and
      others) were present in 29 patients (85%). Twenty of 25 patients with long-term
      follow-up data received immunotherapy (intravenous immunoglobulin in 10 and
      corticosteroids and intravenous immunoglobulin or other immunosuppressors in 10),
      and 7 of them (35%) improved. Predictors of clinical response included subacute
      onset of CA (odds ratio [OR], 0.50; 95% CI, 0.25-0.99; P = .047) and prompt
      immunotherapy (OR, 0.98; 95% CI, 0.96-0.99; P = .01). Similar frequencies of
      serum GAD67-Abs were found in patients with CA (24 of 34 patients [71%]) and in
      patients with stiff person syndrome (20 of 28 patients [71%]). However, GAD67-Abs
      were found in all of the cerebrospinal fluid samples examined (22 samples from
      patients with CA and 17 samples from patients with stiff person syndrome).
      Glycine receptor antibodies but not other cell surface antibodies were identified
      in 4 patients with CA. The presence of glycine receptor antibodies did not
      correlate with any specific clinical feature. CONCLUSIONS AND RELEVANCE: In
      patients with CA and GAD65-Abs, subacute onset of symptoms and prompt
      immunotherapy are associated with good outcome. Persistent vertigo or brainstem
      and cerebellar episodes can herald CA and should lead to GAD65-Ab testing,
      particularly in patients with systemic organ-specific autoimmunities.

PMID- 24934146
TI  - When to repatriate? Clinicians' perspectives on the transfer of patient
      management from specialty to primary care.
AB  - BACKGROUND: Subspecialty ambulatory care visits have doubled in the past 10 years
      and nearly half of all visits are for follow-up care. Could some of this care be
      provided by primary care providers (PCPs)? OBJECTIVE: To determine how often PCPs
      and specialists agree that a mutual patient's condition could be managed
      exclusively by the PCP, and to understand PCPs' perspectives on factors that
      influence decisions about 'repatriation,' or the transfer of patient management
      to primary care. DESIGN: A mixed method approach including paired surveys of PCPs
      and specialists about the necessity for ongoing specialty care of mutual
      patients, and interviews with PCPs about care coordination practices and reasons
      for differing opinions with specialists. PARTICIPANTS: One hundred and eighty
      nine PCPs and 59 physicians representing five medicine subspecialties completed
      paired surveys for 343 patients. Semi-structured interviews were conducted with
      16 PCPs. MEASUREMENTS: For each patient, PCPs and specialists were asked, "Could
      this diagnosis be managed exclusively by the PCP?" RESULTS: Specialists and PCPs
      agreed that transfer to primary care was appropriate for 16% of patients, whereas
      36% had specialists and PCPs who agreed that ongoing specialty care was
      appropriate. Specialists were half as likely as PCPs to identify patients as
      appropriate for transfer to primary care. PCPs identified several factors that
      influence the likelihood that patients will be transferred to primary care,
      including perceived patient preferences, limited access to physician
      appointments, excessive workload, inter-clinician communication norms, and
      differences in clinical judgment. We group these factors into two domains: 'push
      back' and 'pull-back' to primary care. CONCLUSIONS: At a large academic medical
      center, approximately one in six patients receiving ongoing specialty care could
      potentially be managed exclusively by a PCP. PCPs identified several non-clinical
      factors to explain continuation of specialty care when patient transfer to PCP is
      clinically appropriate.

PMID- 24934148
TI  - Validity of the relativistic phase shift model for the extrinsic spin Hall effect
      in dilute metal alloys.
AB  - Recently, a generalized relativistic phase shift model was proposed (Fedorovet al
      2013 Phys. Rev. B 88 085116) for the description of the skew-scattering
      contribution to the spin Hall effect caused by impurities. Here, we inspect this
      model by means of a systematic comparison with the results of first-principles
      calculations performed for several metallic host systems with different
      substitutional impurities. It is found that for its proper application, the
      differences between impurity and host phase shifts should be used as input
      parameters. Generally, the model provides good qualitative agreement with ab
      initio results for hosts with a free-electron-like Fermi surface and a relatively
      weak spin-orbit coupling, but fails otherwise. 

PMID- 24934147
TI  - Walking cadence and mortality among community-dwelling older adults.
AB  - BACKGROUND: Older adults are encouraged to walk >=100 steps?minute(-1) for
      moderate-intensity physical activity (i.e., brisk walking). It is unknown if the
      ability to walk >=100 steps?minute(-1) predicts mortality. OBJECTIVE: To
      determine if the ability to walk >=100 steps?minute(-1) predicts mortality among
      older adults. DESIGN, SETTING, AND PATIENTS: A population-based cohort study
      among 5,000 older adults from the Third National Health and Nutrition Survey
      (NHANES III; 1988-1994). Vital status and cause of death were collected through
      December 31, 2006. Median follow-up was 13.4 years. Average participant age was
      70.6 years. MEASUREMENTS: Walking cadence (steps?minute(-1)) was calculated using
      a timed 2.4-m walk. Walking cadence was dichotomized at 100 steps?minute(-1)
      (>=100 steps?minute(-1) versus <100 steps?minute(-1)) to demarcate the lower
      threshold of absolutely defined moderate-intensity physical activity. Walking
      cadence was also analyzed as a continuous variable. Predicted survival was
      compared between walking cadence and gait speed. The primary outcome was all
      cause mortality. Secondary outcomes included cardiovascular-specific and cancer
      specific mortality and mortality from other causes. RESULTS: Among 5,000
      participants, 3,039 (61 %) walked >=100 steps?minute(-1). During follow-up, 3,171
      subjects died. In multivariable-adjusted analysis, ability to walk >=100
      steps?minute(-1) predicted a 21 % reduction in all-cause mortality (hazard ratio
      [HR], 0.79; 95 % confidence interval [95 % CI], 0.71-0.89, p < 0.001). Each ten
      step increase in walking cadence predicted a 4 % reduction in all-cause mortality
      (HR, 0.96, [0.94-0.98], p < 0.001). In secondary analyses, ability to walk >=100
      steps?minute(-1) predicted reductions in cardiovascular-specific mortality (HR,
      0.79 [0.67-0.92], p = 0.002), cancer-specific mortality (HR, 0.76 [0.58-0.99], p
      = 0.050), and mortality from other causes (HR, 0.82 [0.68-0.97], p = 0.025).
      Predicted survival, adjusted for age and sex, was not different using walking
      cadence versus gait speed. LIMITATIONS: Walking cadence was a cross-sectional
      measurement. CONCLUSIONS: The ability to walk >=100 steps?minute(-1) predicts a
      reduction in mortality among a sample of community-dwelling older adults.

PMID- 24934149
TI  - Adsorption-based immobilization of Caldicellulosiruptor saccharolyticus
      cellobiose 2-epimerase on Bacillus subtilis spores.
AB  - Nonrecombinant spore was examined as a novel immobilization support to adsorb
      enzymes. Caldicellulosiruptor saccharolyticus cellobiose 2-epimerase (CsCE),
      efficiently producing lactulose using lactose as a single substrate, was
      immobilized on Bacillus subtilis spores via adsorption. The immobilization
      process was optimized, and the properties of immobilized CsCE and the
      interactions between the enzyme and spores were also investigated. Under the
      optimized conditions (pH 4.5, temperature 4  degrees C, reaction time 2 H, and
      initial enzyme concentration 2.4 mg/mL), the maximum adsorbed amount of CsCE was
      1.47 mg/10(11) spores, and the enzyme activity recovery was 79.4%. The spore
      immobilized CsCE presented a higher pH and thermal stability than a free enzyme.
      Total desorption of the immobilized enzyme was only achieved by treatment with
      1.0 M NaCl at pH 1.0, indicating a strong adsorption between CsCE and B. subtilis
      spores. Efficient binding may require a potent combination of electrostatic and
      hydrophobic interactions between spores and an enzyme. The immobilized CsCE was
      applied to produce 395 g/L lactulose after 4 H. Moreover, the spores could be
      regenerated and the spore-immobilized enzyme showed good reusability as it
      retained approximately 70% of its initial activity after eight recycles.

PMID- 24934150
TI  - Measuring health-related quality of life in chronic obstructive pulmonary
      disease: properties of the EQ-5D-5L and PROMIS-43 short form.
AB  - BACKGROUND: The Patient Reported Outcomes Measurement Information System 43-item
      short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed
      measures of health-related quality of life (HRQL) that have potentially broad
      application in evaluating treatments and capturing burden of respiratory-related
      diseases. The aims of this study were: (1) to examine their psychometric
      properties in patients with chronic obstructive pulmonary disease (COPD), and (2)
      to identify dimensions of HRQL that differ and do not differ by lung function.
      METHODS: We conducted a multi-center, cross-sectional study ("COPD Outcomes-based
      Network for Clinical Effectiveness & Research Translation" [CONCERT]). We
      analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L
      and PROMIS questionnaires. Disease severity was graded based on the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Pulmonary
      function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ
      VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT
      Dyspnea) were administered. Validity and reliability of EQ-5D-5L and PROMIS-43
      were examined, and differences in HRQL by GOLD grade were assessed. RESULTS: Data
      from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male). More
      severe COPD was associated with more problems with mobility, self-care and usual
      activities (all p-values <0.01) according to EQ-5D-5L. Related domains on EQ-5D
      5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r
      >= 0.50) correlated. A statistically significant trend of decreasing HRQL with
      more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores,
      and PROMIS physical function and social roles. CONCLUSIONS: Results supported the
      validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical
      function and social activities decrease with level of lung function by GOLD
      grade, but not pain, mental health, sleep or fatigue as reported by patients.

PMID- 24934151
TI  - Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial
      progenitor cells in coronary artery disease patients.
AB  - BACKGROUND: Circulating endothelial progenitor cells (EPCs) may be a biomarker
      for vascular function and cardiovascular risk in patients with coronary artery
      disease (CAD). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) regulates the
      function of EPCs. This study aimed to examine whether hypermethylation of DDAH2
      promoter contributes to impaired function of EPCs in CAD patients. METHODS:
      Peripheral blood mono-nuclear cells from 25 CAD patients and 15 healthy
      volunteers were collected and differentiated into EPCs. EPCs were tested for
      their adhesive capability. DDAH2 mRNA expression was analyzed by real-time PCR,
      and the methylation of DDAH2 promoter was detected by bisulfite genomic
      sequencing. RESULTS: DDAH2 promoter in EPCs from CAD patients was hypermethylated
      and the methylation level was negatively correlated to DDAH2 mRNA level and
      adhesion function of EPCs. Homocysteine impaired the adhesion function of EPCs,
      accompanied by lower DDAH2 expression and higher methylation level of DDAH2
      promoter, compared to controls. These effects of homocysteine were reversed by
      pretreatment with Aza, an inhibitor of DNA methyltransferase. CONCLUSION:
      Hypermethylation in DDAH2 promoter is positively correlated to the dysfunction of
      EPCs in CAD patients. Homocysteine disrupts EPCs function via inducing the
      hypermethylation of DDAH2 promoter, suggesting a key role of epigenetic mechanism
      in the progression of atherosclerosis.

PMID- 24934153
TI  - Class III correction using an inter-arch spring-loaded module.
AB  - BACKGROUND: A retrospective study was conducted to determine the cephalometric
      changes in a group of Class III patients treated with the inter-arch spring
      loaded module (CS2000(r), Dynaflex, St. Ann, MO, USA). METHODS: Thirty Caucasian
      patients (15 males, 15 females) with an average pre-treatment age of 9.6 years
      were treated consecutively with this appliance and compared with a control group
      of subjects from the Bolton-Brush Study who were matched in age, gender, and
      craniofacial morphology to the treatment group. Lateral cephalograms were taken
      before treatment and after removal of the CS2000(r) appliance. The treatment
      effects of the CS2000(r) appliance were calculated by subtracting the changes due
      to growth (control group) from the treatment changes. RESULTS: All patients were
      improved to a Class I dental arch relationship with a positive overjet.
      Significant sagittal, vertical, and angular changes were found between the pre-
      and post-treatment radiographs. With an average treatment time of 1.3 years, the
      maxillary base moved forward by 0.8 mm, while the mandibular base moved backward
      by 2.8 mm together with improvements in the ANB and Wits measurements. The
      maxillary incisor moved forward by 1.3 mm and the mandibular incisor moved
      forward by 1.0 mm. The maxillary molar moved forward by 1.0 mm while the
      mandibular molar moved backward by 0.6 mm. The average overjet correction was 3.9
      mm and 92% of the correction was due to skeletal contribution and 8% was due to
      dental contribution. The average molar correction was 5.2 mm and 69% of the
      correction was due to skeletal contribution and 31% was due to dental
      contribution. CONCLUSIONS: Mild to moderate Class III malocclusion can be
      corrected using the inter-arch spring-loaded appliance with minimal patient
      compliance. The overjet correction was contributed by forward movement of the
      maxilla, backward and downward movement of the mandible, and proclination of the
      maxillary incisors. The molar relationship was corrected by mesialization of the
      maxillary molars, distalization of the mandibular molars together with a rotation
      of the occlusal plane.

PMID- 24934152
TI  - Minimally invasive plate osteosynthesis with a locking compression plate is
      superior to open reduction and internal fixation in the management of the
      proximal humerus fractures.
AB  - BACKGROUND: The use of minimally invasive plate osteosynthesis (MIPO) via
      anterolateral deltoid splitting has good outcomes in the management of proximal
      humerus fractures. While using this approach has several advantages, including
      minimal soft tissue disruption, preservation of natural biology and minimal blood
      loss, there is an increased risk for axillary nerve damage. This study compared
      the advantages and clinical and radiological outcomes of MIPO or open reduction
      and internal fixation (ORIF) in patients with proximal humerus fractures.
      METHODS: A matched-pair analysis was performed, and patient groups were matched
      according to age (+/-3 years), sex and fracture type. Forty-three pairs of
      patients (average age: MIPO, 63 and ORIF, 61) with a minimum follow-up of 12
      months were enrolled in the study group. The patients were investigated
      radiographically and clinically using the Constant score. RESULTS: The MIPO
      technique required less surgery time and caused less blood loss compared to ORIF
      (p < 0.01). In addition, MIPO required a smaller incision, resulted in less
      scarring, and was cosmetically more appealing and acceptable to female patients
      than ORIF. Following MIPO, patients had better functional results at 3 and 6
      months, with better outcomes, less pain, higher satisfaction in activities of
      daily living, and a higher range of motion when compared to ORIF (p < 0.05).
      Fracture configuration, according to the AO/ASIF(Association for the Study of
      Internal Fixation) fracture classification, did not significantly influence the
      functional results. The complication rate was comparable between both groups.
      CONCLUSION: The use of MIPO with a locking compression plate in the management of
      proximal humerus fractures is a safe and superior option compared to ORIF.

PMID- 24934154
TI  - A single domain of the ZP2 zona pellucida protein mediates gamete recognition in
      mice and humans.
AB  - The extracellular zona pellucida surrounds ovulated eggs and mediates gamete
      recognition that is essential for mammalian fertilization. Zonae matrices contain
      three (mouse) or four (human) glycoproteins (ZP1-4), but which protein binds
      sperm remains controversial. A defining characteristic of an essential zona
      ligand is sterility after genetic ablation. We have established transgenic mice
      expressing human ZP4 that form zonae pellucidae in the absence of mouse or human
      ZP2. Neither mouse nor human sperm bound to these ovulated eggs, and these female
      mice were sterile after in vivo insemination or natural mating. The same
      phenotype was observed with truncated ZP2 that lacks a restricted domain within
      ZP2(51-149). Chimeric human/mouse ZP2 isoforms expressed in transgenic mice and
      recombinant peptide bead assays confirmed that this region accounts for the taxon
      specificity observed in human-mouse gamete recognition. These observations in
      transgenic mice document that the ZP2(51-149) sperm-binding domain is necessary
      for human and mouse gamete recognition and penetration through the zona
      pellucida. 

PMID- 24934155
TI  - Mps1 phosphorylation of condensin II controls chromosome condensation at the
      onset of mitosis.
AB  - During mitosis, genomic DNA is condensed into chromosomes to promote its equal
      segregation into daughter cells. Chromosome condensation occurs during cell cycle
      progression from G2 phase to mitosis. Failure of chromosome compaction at
      prophase leads to subsequent misregulation of chromosomes. However, the molecular
      mechanism that controls the early phase of mitotic chromosome condensation is
      largely unknown. Here, we show that Mps1 regulates initial chromosome
      condensation during mitosis. We identify condensin II as a novel Mps1-associated
      protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492
      during mitosis, and this phosphorylation event is required for the proper loading
      of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of
      condensin II and accurate chromosome condensation during prophase. These findings
      demonstrate that Mps1 governs chromosomal organization during the early stage of
      mitosis to facilitate proper chromosome segregation. 

PMID- 24934156
TI  - HDAC4 integrates PTH and sympathetic signaling in osteoblasts.
AB  - Parathyroid hormone (PTH) and the sympathetic tone promote Rankl expression in
      osteoblasts and osteoclast differentiation by enhancing cyclic adenosine
      monophosphate production through an unidentified transcription factor for PTH and
      through ATF4 for the sympathetic tone. How two extracellular cues using the same
      second messenger in the same cell elicit different transcriptional events is
      unknown. In this paper, we show that PTH favors Rankl expression by triggering
      the ubiquitination of HDAC4, a class II histone deacetylase, via Smurf2. HDAC4
      degradation releases MEF2c, which transactivates the Rankl promoter. Conversely,
      sympathetic signaling in osteoblasts favors the accumulation of HDAC4 in the
      nucleus and its association with ATF4. In this context, HDAC4 increases Rankl
      expression. Because of its ability to differentially connect two extracellular
      cues to the genome of osteoblasts, HDAC4 is a critical regulator of osteoclast
      differentiation. 

PMID- 24934159
TI  - Sudden neuropathological deaths: An autopsy study.
AB  - BACKGROUND: Sudden or unexpected death can occur from unnatural causes, such as
      violence or poisoning, as well as from natural causes. Second to cardiac causes,
      neuropathology is one of the main causes of sudden natural death. In spite of the
      increasing incidence of neuropathological deaths, few studies have been conducted
      in Asia - hence the reason for the present study. METHODS: A 10-year (January
      2003 to December 2012) retrospective study was conducted at the MS medico-legal
      institute in a metropolitan city of southern India. All the cases of sudden
      natural death, where the cause of death was opined to be due to a neuropathology
      after meticulous medico-legal autopsy and chemical analysis, were included.
      RESULTS AND CONCLUSIONS: A total of 7520 reported deaths were investigated. These
      included 291 sudden natural deaths, amongst which the death was attributed to
      neuropathology in 43 cases (14.7%). Of these 43 cases, 69.7% were male and 30.3%
      were female. The majority of cases (25.5%) were in those aged >=60 years. Causes
      of neuropathology were due to subarachnoid haemorrhage in 48.8% of cases, stroke
      in 30.2%, meningitis in 14% and tumours in 7%. There was history of hypertension
      in 46.5% of cases, diabetes in 32.5% of cases and cardiac disease in 18.6% of
      cases.

PMID- 24934157
TI  - The Cavbeta1a subunit regulates gene expression and suppresses myogenin in muscle
      progenitor cells.
AB  - Voltage-gated calcium channel (Cav) beta subunits are auxiliary subunits to Cavs.
      Recent reports show Cavbeta subunits may enter the nucleus and suggest a role in
      transcriptional regulation, but the physiological relevance of this localization
      remains unclear. We sought to define the nuclear function of Cavbeta in muscle
      progenitor cells (MPCs). We found that Cavbeta1a is expressed in proliferating
      MPCs, before expression of the calcium conducting subunit Cav1.1, and enters the
      nucleus. Loss of Cavbeta1a expression impaired MPC expansion in vitro and in vivo
      and caused widespread changes in global gene expression, including up-regulation
      of myogenin. Additionally, we found that Cavbeta1a localizes to the promoter
      region of a number of genes, preferentially at noncanonical (NC) E-box sites.
      Cavbeta1a binds to a region of the Myog promoter containing an NC E-box,
      suggesting a mechanism for inhibition of myogenin gene expression. This work
      indicates that Cavbeta1a acts as a Cav-independent regulator of gene expression
      in MPCs, and is required for their normal expansion during myogenic development. 

PMID- 24934160
TI  - Effect of simulated resistance, fleeing, and use of force on standardized field
      sobriety testing.
AB  - INTRODUCTION: When a law enforcement officer (LEO) stops a suspect believed to be
      operating (a vehicle) while impaired (OWI), the suspect may resist or flee, and
      the LEO may respond with force. The suspect may then undergo a Standardized Field
      Sobriety Test (SFST) to gauge impairment. It is not known whether resistance,
      fleeing, or actions of force can create an inaccurate SFST result. We examined
      the effect of resistance, fleeing, and force on the SFST. MATERIALS AND METHODS:
      Human volunteers were prospectively randomized to have a SFST before and after
      one of five scenarios: (1) five-second conducted electrical weapon exposure; (2)
      100-yard (91.4 m) sprint; (3) 45-second physical fight; (4) police dog bite with
      protective gear; and (5) Oleoresin Capsicum spray to the face with eyes shielded.
      The SFST was administered and graded by a qualified LEO. After the SFST, the
      volunteer entered their scenario and was then administered another SFST. Data
      were analyzed using descriptive statistics. SFST performance was compared before
      and after using chi-square tests. RESULTS: Fifty-seven subjects enrolled. Three
      received a single-point penalty during one component of the three-component SFST
      pre-scenario. No subject received a penalty point in any components of the SFST
      post-scenario (p = 0.08). CONCLUSIONS: This is the first human study to examine
      the effects of physical resistance, flight, and use of force on the SFST result.
      We did not detect a difference in the performance of subjects taking the SFST
      before and after exposure to resistance, flight, or a simulated use of force.

PMID- 24934161
TI  - Hydranencephaly in a case of suspected infanticide.
AB  - An abandoned fetus with suspicious skin injuries was found dead, lying on the
      grass of a garden, near a private house. Suspecting infanticide, the prosecutor
      ordered a medico-legal autopsy. The cause of death was identified as a congenital
      malformation of the central nervous system such as hydranencephaly, and
      infanticide was excluded. 

PMID- 24934158
TI  - Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive
      utility of precision cut lung slices.
AB  - BACKGROUND: Emissions from a large peat fire in North Carolina in 2008 were
      associated with increased hospital admissions for asthma and the rate of heart
      failure in the exposed population. Peat fires often produce larger amounts of
      smoke and last longer than forest fires, however few studies have reported on
      their toxicity. Moreover, reliable alternatives to traditional animal toxicity
      testing are needed to reduce the number of animals required for hazard
      identification and risk assessments. METHODS: Size-fractionated particulate
      matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while
      smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were
      analyzed for chemical constituents and endotoxin content. Female CD-1 mice were
      exposed via oropharyngeal aspiration to 100 MUg/mouse, and assessed for relative
      changes in lung and systemic markers of injury and inflammation. At 24 h post
      exposure, hearts were removed for ex vivo functional assessments and ischemic
      challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 MUg)
      +/- co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound.
      RESULTS: On an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin
      content and elicited the greatest pro-inflammatory responses in the mice
      including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6,
      TNF-alpha, and MIP-2), neutrophils and intracellular reactive oxygen species
      (ROS) production. Exposure to fine or ultrafine particles from either period
      failed to elicit significant lung or systemic effects. In contrast, mice exposed
      to ENCF-1 ultrafine PM developed significantly decreased cardiac function and
      greater post-ischemia-associated myocardial infarction. Finally, similar
      exposures to mouse lung slices induced comparable patterns of cytokine
      production; and these responses were significantly attenuated by PMB.
      CONCLUSIONS: The findings suggest that exposure to coarse PM collected during a
      peat fire causes greater lung inflammation in association with endotoxin and ROS,
      whereas the ultrafine PM preferentially affected cardiac responses. In addition,
      lung tissue slices were shown to be a predictive, alternative assay to assess pro
      inflammatory effects of PM of differing size and composition. Importantly, these
      toxicological findings were consistent with the cardiopulmonary health effects
      noted in epidemiologic reports from exposed populations.

PMID- 24934162
TI  - An unusual case of homicide with a crossbow and a hunting knife.
AB  - Traumatic lethal injuries caused by crossbows are a rarity in forensic pathology.
      They occur as accidents, suicide and, more rarely, as murders. We report a case
      of murder received at the Institute of Legal Medicine in Milan carried out by two
      weapons - a crossbow and a hunting knife - that resulted in multiple thoraco
      abdominal wounds. The case is also rare because of the unique circumstances
      involving the victim - a local service psychiatrist - and the perpetrator - a
      former medical specialist in psychiatry, suffering from a delusional psychotic
      disorder. The crossbow was the decisive instrument in the realization of the
      murder; it was chosen with premeditation for its high destructive capacity and
      the fact that it was easily obtainable, and it was used with darts that were
      specially modified to increase its harmful capacity. The presented case, as well
      as providing an opportunity to highlight the damaging effects of a rarely used
      weapon, stresses the problems inherent with access to tools such as the crossbow
      that are used in sport, and which are potentially dangerous but easily
      accessible, even to those with serious mental disorders, rendering them legally
      unfit for using firearms. 

PMID- 24934164
TI  - eHealth and mHealth initiatives in Bangladesh: a scoping study.
AB  - BACKGROUND: The health system of Bangladesh is haunted by challenges of
      accessibility and affordability. Despite impressive gains in many health
      indicators, recent evidence has raised concerns regarding the utilization,
      quality and equity of healthcare. In the context of new and unfamiliar public
      health challenges including high population density and rapid urbanization,
      eHealth and mHealth are being promoted as a route to cost-effective, equitable
      and quality healthcare in Bangladesh. The aim of this paper is to highlight such
      initiatives and understand their true potential. METHODS: This scoping study
      applies a combination of research tools to explore 26 eHealth and mHealth
      initiatives in Bangladesh. A screening matrix was developed by modifying the
      framework of Arksey & O'Malley, further complemented by case study and SWOT
      analysis to identify common traits among the selected interventions. The WHO
      health system building blocks approach was then used for thematic analysis of
      these traits. RESULTS: Findings suggest that most eHealth and mHealth initiatives
      have proliferated within the private sector, using mobile phones. The most common
      initiatives include tele-consultation, prescription and referral. While a
      minority of projects have a monitoring and evaluation framework, less than a
      quarter have undertaken evaluation. Most of the initiatives use a health
      management information system (HMIS) to monitor implementation. However, these do
      not provide for effective sharing of information and interconnectedness among the
      various actors. There are extremely few individuals with eHealth training in
      Bangladesh and there is a strong demand for capacity building and experience
      sharing, especially for implementation and policy making. There is also a lack of
      research evidence on how to design interventions to meet the needs of the
      population and on potential benefits. CONCLUSION: This study concludes that
      Bangladesh needs considerable preparation and planning to sustain eHealth and
      mHealth initiatives successfully. Additional formative and operational research
      is essential to explore the true potential of the technology. Frameworks for
      regulation in regards to eHealth governance should be the aim of future research
      on the integration of eHealth and mHealth into the Bangladesh health system.

PMID- 24934163
TI  - Life-space mobility and mortality in older men: a prospective cohort study.
AB  - OBJECTIVES: To evaluate the relationship between life-space (the extent,
      frequency, and independence of an individual's movement) and mortality in older
      men. DESIGN: Prospective cohort study. SETTING: Six U.S. clinical sites.
      PARTICIPANTS: Men aged 71 to 98 followed from 2007 to 2011 (N = 3,892).
      MEASUREMENTS: Life-space during the past month was assessed as 0 (daily
      restriction to one's bedroom) to 120 (daily trips outside one's town without
      assistance) and categorized into 20-point intervals. The primary outcome was
      noncancer mortality, and secondary outcomes were all-cause, cardiovascular,
      cancer, and noncardiovascular noncancer mortality. RESULTS: Over 2.7 years (2007
      2011), 373 (9.6%) men died, 230 from noncancer causes. Unadjusted risk of
      noncancer mortality was 41.2% in men with the lowest level of life-space (0-20
      points, n = 34) and 2.4% in men with the highest level of life-space (101-120
      points, n = 868), a 17 times difference. In multivariable-adjusted models, there
      was a strong linear trend between decreasing life-space and increasing risk of
      noncancer mortality (P = .005). Risk of noncancer mortality was 3.8 times higher
      (95% confidence interval (CI)=1.3,11.5) in men with the lowest life-space than in
      those with the highest life-space. Risk of noncancer mortality was 1.3 times
      higher (95% CI=1.1-1.5) for each standard-deviation (24 point) decrease in life
      space. Risk of noncancer mortality was 1.5 times higher (95% CI=1.0-2.3) in men
      who did not travel beyond their neighborhood without assistance (n = 471).
      Results were similar for all-cause mortality and did not change after control for
      chronic disease burden. CONCLUSION: Life-space predicted a variety of mortality
      endpoints in older men; scores of 40 or less were associated with mortality
      independent of other risk factors.

PMID- 24934165
TI  - Modulation of Doxorubicin mediated growth inhibition of hepatocellular carcinoma
      cells by platelet lysates.
AB  - PURPOSE: Platelet extracts can stimulate cell growth and contribute to tumor
      biology. It was recently shown that they stimulate the growth of hepatocellular
      carcinoma (HCC) cells and decrease apoptosis. Doxorubicin is a commonly used HCC
      chemotherapy that increases apoptosis. We therefore examined the effects of
      platelet lysates (hPL) on doxorubicin-mediated HCC cell growth inhibition and
      apoptosis induction. METHODS: Three human HCC cell lines, PLC/PRF/5, Hep3B and
      HepG2 cells, were grown in culture and growth was measured by the MTT assay and
      apoptosis was measured using Muse Annexin V assay kit. Cells were also probed by
      Western blot. RESULTS: hPL decreased doxorubicin-mediated growth inhibition and
      apoptosis induction in all three cell lines. When doxorubicin and hPL were added
      at separate time intervals, protection by hPL was also observed. WB showed that
      hPL caused prolonged and increased levels of phospho-JNK and phospho-p38.
      Furthermore, a p38 inhibitor abrogated the modulating effects of hPL on both
      growth and apoptosis, indicating its importance in mediating hPL actions. WBs
      also showed that hPL decreased doxorubicin-induced markers of apoptosis.
      CONCLUSIONS: hPL modulate the actions of the cancer chemotherapeutic agent,
      doxorubicin. Platelets are part of the complex microenvironmental milieu and
      their effects may contribute to a modulation of chemotherapy actions. Conversely,
      drugs that alter platelet levels or degranulation could potentially augment
      doxorubicin actions on HCC cells.

PMID- 24934166
TI  - Protein transport into the human ER and related diseases, Sec61-channelopathies.
AB  - Protein transport into the human endoplasmic reticulum (ER) is relevant to the
      biogenesis of most soluble and membrane proteins of organelles, which are
      involved in endo- or exo-cytsosis. It involves amino-terminal signal peptides in
      the precursor polypeptides and various transport components in the cytosol plus
      the ER, and can occur co- or post-translationally. The two mechanisms merge at
      the level of the ER membrane, specifically at the level of the heterotrimeric
      Sec61 complex, which forms a dynamic polypeptide-conducting channel in the ER
      membrane. Since the mammalian ER is also the main intracellular calcium storage
      organelle, and the Sec61 complex is calcium permeable, the Sec61 complex is
      tightly regulated in its equilibrium between the closed and open conformations,
      or "gated", by ligands, such as signal peptides of the transport substrates and
      the ER lumenal Hsp70-type molecular chaperone BiP. Furthermore, BiP binding to
      the incoming polypeptide contributes to the efficiency and unidirectionality of
      transport. Recent insights into the structure and dynamic equilibrium of the
      Sec61 complex have various mechanistic as well as medical implications. 

PMID- 24934167
TI  - Impact of routine use of surgical drains on incidence of complications with robot
      assisted radical prostatectomy.
AB  - PURPOSE: To assess the impact of eliminating routine drain placement in patients
      undergoing robot-assisted laparoscopic prostatectomy (RALP) and pelvic lymph node
      dissection (PLND) on the risk of postoperative complications. PATIENTS AND
      METHODS: An experienced single surgeon performed RALP on 651 consecutive patients
      at our institution from 2008 to 2012. Before August 2011, RALP with or without
      PLND included a routine peritoneal drain placed during surgery. Thereafter,
      routine intraoperative placement of drains was omitted, except for
      intraoperatively noted anastomotic leakage. We used multivariable logistic
      regression to compare complication rates between study periods and the actual
      drain placement status after adjusting for standard prespecified covariates.
      RESULTS: Most patients (92%) did not have >=grade 2 complications after surgery
      and only two patients (0.3%) experienced a grade 4 complication. The absolute
      adjusted risk of a grade 2-5 complication was 0.9% greater among those treated
      before August 2011 (95% confidence interval [CI] -3.3%-5.1%; p=0.7), while
      absolute adjusted risk of a grade 3-5 complication was 2.8% less (-2.8%; 95% CI
      5.3%-0.1%; p=0.061). RESULTS based on drain status were similar. CONCLUSIONS:
      Routine peritoneal drain placement following RALP with PLND did not confer a
      significant advantage in terms of postoperative complications. Further data are
      necessary to confirm that it is safe to omit drains in most patients.

PMID- 24934168
TI  - Cannabinoid-free Cannabis sativa L. grown in the Po valley: evaluation of fatty
      acid profile, antioxidant capacity and metabolic content.
AB  - Within a project aimed to reintroduce non-drug hemp cultivars in the Italian Po
      valley, for fibre but also high added-value nutraceutical production,
      investigation on locally grown plants has been performed, in order to assess
      their oil and metabolic content. This study provides useful information regarding
      three different hemp cultivars, from two sites, in view of their potential
      industrial application. The oil was characterised by a high unsaturated/saturated
      fatty acid ratio and by an almost perfect balance of omega-3 and omega-6 fatty
      acids, as requested for healthy foods. The alcoholic extracts, for which a high
      content of amino acids and phenolic compounds has been highlighted, could provide
      dietary supplements to help in preventing oxidative stress. By investigating the
      Carmagnola cultivar, six known and four new lignanamides have been identified,
      confirming and assessing the general metabolic pattern in the seeds of these
      locally grown plants. 

PMID- 24934169
TI  - Axillary reverse mapping: Is it feasible in locally advanced breast cancer
      patients?
AB  - INTRODUCTION: Axillary dissection is associated with a high incidence of
      lymphedema, which has been brought down with the introduction of sentinel lymph
      node biopsy (SLNB) in patients with early breast cancer. However, sentinel lymph
      node biopsy is not widely accepted in patients of locally advanced breast cancer
      (LABC) [T3N1, Any T4, Any N2-3 with no distant metastasis] after neo-adjuvant
      chemotherapy (NACT) and these patients routinely undergo axillary lymph node
      clearance. Axillary reverse mapping (ARM) with blue dye has the potential to
      differentiate the arm lymphatics from the breast lymphatics and it can be used to
      decrease lymphedema in patients undergoing ALND by preserving these lymphatics.
      However, ARM in LABC patients is yet to be accepted as the standard of care.
      MATERIALS AND METHODS: 51 patients of locally advanced breast carcinoma were
      included in the study from May 2011 to May 2012. All patients received neo
      adjuvant chemotherapy followed by modified radical mastectomy. Axillary reverse
      mapping (ARM) was carried out using blue dye. 2 ml of methylene blue dye was
      injected intradermal, upper medial aspect of the ipsilateral arm. The number,
      size and site and distribution of lymph nodes identified were recorded and the
      nodes were labelled as ARM nodes and complete axillary dissection was carried
      out. RESULTS: Blue nodes were identified in 45 (88.2%) out of the 51 patients.
      The average number of ARM nodes identified was 4.03 +/- 0.28 [range 1-8]. In
      majority (77.8%) of the cases, nodes were located in the triangle formed by
      axillary vein above, below by the first intercostobrachial nerve and medially by
      the chest wall/serratus anterior. In patients with complete or partial response
      to NACT, ARM and breast axillary LN were negative in 63.3% patients whereas 36.6%
      had positive breast but negative ARM nodes. In this study we did not intend to
      preserve any ARM nodes but in 90% of these cases, at least one ARM node had to be
      removed or was injured during axillary clearance. ARM nodes could be identified
      in 15 (83.3%) out of the 18 patients with stable or progressive disease following
      ARM. 12 (80%) out of these 15 cases demonstrated positive ARM and breast LN
      whereas 3 (20%) patients had positive breast but negative ARM nodes. Skin
      tattooing (82.3%) was the most common complication observed in our study.
      CONCLUSIONS: Identification rates of ARM nodes can be improved by injecting the
      blue dye in the upper medial aspect of the arm at the time of induction. Majority
      of the arm nodes lie between the axillary vein and the first intercostobrachial
      nerve. It is difficult to preserve the ARM nodes in patients of LABC, who have
      had good response to NACT and in patients of LABC with poor response to NACT, the
      incidence of metastasis in ARM nodes is quite high. Therefore, ARM is not a
      feasible option in patients with locally advanced breast cancer.

PMID- 24934171
TI  - Using the Knowledge, Process, Practice (KPP) model for driving the design and
      development of online postgraduate medical education.
AB  - BACKGROUND: Online learning is a primary delivery method for continuing health
      education programs. It is critical that programs have curricula objectives linked
      to educational models that support learning. Using a proven educational modelling
      process ensures that curricula objectives are met and a solid basis for learning
      and assessment is achieved. AIM: To develop an educational design model that
      produces an educationally sound program development plan for use by anyone
      involved in online course development. METHODS: We have described the development
      of a generic educational model designed for continuing health education programs.
      The Knowledge, Process, Practice (KPP) model is founded on recognised educational
      theory and online education practice. This paper presents a step-by-step guide on
      using this model for program development that encases reliable learning and
      evaluation. RESULTS: The model supports a three-step approach, KPP, based on
      learning outcomes and supporting appropriate assessment activities. It provides a
      program structure for online or blended learning that is explicit, educationally
      defensible, and supports multiple assessment points for health professionals.
      CONCLUSION: The KPP model is based on best practice educational design using a
      structure that can be adapted for a variety of online or flexibly delivered
      postgraduate medical education programs.

PMID- 24934170
TI  - Characterizing breast cancer treatment pathways in Kumasi, Ghana from onset of
      symptoms to final outcome: outlook towards cancer control.
AB  - BACKGROUND: Cancer rates are increasing in Africa, including Ghana. Breast cancer
      is the second most common cancer in incidence and mortality in Ghana. OBJECTIVE:
      We outlined both breast cancer patient characteristics and management at the
      Komfo Anokye Teaching Hospital (KATH), the main cancer management hospital in
      central Ghana. Moreover, we identified the treatment interventions predictive of
      patient outcome. METHODS: Medical records of 597 breast cancer patients seen in
      2008-2011 were abstracted to investigate management and treatment patterns.
      Abstracted variables included type and extent of surgery, number and cycles of
      chemotherapy and radiotherapy, as well as the course of treatment completed.
      RESULTS: Late stage at diagnosis was common, treatment plans of the study
      hospital were relatively standardized according to disease severity, and
      defaulting/interrupting treatment in the records was also common. Patients
      diagnosed with late stage cancer who received adjuvant therapy and patients with
      hormone status evaluation were more likely to have complied with treatment
      guidelines and continued oncotherapy at the study hospital than those who never
      had hormone status requested or reported. CONCLUSIONS: Our study lends support to
      improving patient outcomes in low- and middle-income countries through raising
      knowledge and reporting of tumor hormonal status and providing appropriately
      tailored treatment. Achieving improved outcomes should also consider enhancing
      public understanding of the importance of early detection and completion of
      treatment.

PMID- 24934172
TI  - Subcellular Relocalization and Positive Selection Play Key Roles in the Retention
      of Duplicate Genes of Populus Class III Peroxidase Family.
AB  - Gene duplication is the primary source of new genes and novel functions. Over the
      course of evolution, many duplicate genes lose their function and are eventually
      removed by deletion. However, some duplicates have persisted and evolved diverse
      functions. A particular challenge is to understand how this diversity arises and
      whether positive selection plays a role. In this study, we reconstructed the
      evolutionary history of the class III peroxidase (PRX) genes from the Populus
      trichocarpa genome. PRXs are plant-specific enzymes that play important roles in
      cell wall metabolism and in response to biotic and abiotic stresses. We found
      that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell
      wall type PRX to vacuole type, followed by tandem duplications and subsequent
      functional specification. Substitution models identified seven positively
      selected sites in the vacuole PRXs. These positively selected sites showed
      significant effects on the biochemical functions of the enzymes. We also found
      that positive selection acts more frequently on residues adjacent to, rather than
      directly at, a critical active site of the enzyme, and on flexible regions rather
      than on rigid structural elements of the protein. Our study provides new insights
      into the adaptive molecular evolution of plant enzyme families.

PMID- 24934173
TI  - The Functional Topography of the Arabidopsis Genome Is Organized in a Reduced
      Number of Linear Motifs of Chromatin States.
AB  - Chromatin is of major relevance for gene expression, cell division, and
      differentiation. Here, we determined the landscape of Arabidopsis thaliana
      chromatin states using 16 features, including DNA sequence, CG methylation,
      histone variants, and modifications. The combinatorial complexity of chromatin
      can be reduced to nine states that describe chromatin with high resolution and
      robustness. Each chromatin state has a strong propensity to associate with a
      subset of other states defining a discrete number of chromatin motifs. These
      topographical relationships revealed that an intergenic state, characterized by
      H3K27me3 and slightly enriched in activation marks, physically separates the
      canonical Polycomb chromatin and two heterochromatin states from the rest of the
      euchromatin domains. Genomic elements are distinguished by specific chromatin
      states: four states span genes from transcriptional start sites (TSS) to
      termination sites and two contain regulatory regions upstream of TSS. Polycomb
      regions and the rest of the euchromatin can be connected by two major chromatin
      paths. Sequential chromatin immunoprecipitation experiments demonstrated the
      occurrence of H3K27me3 and H3K4me3 in the same chromatin fiber, within a two to
      three nucleosome size range. Our data provide insight into the Arabidopsis genome
      topography and the establishment of gene expression patterns, specification of
      DNA replication origins, and definition of chromatin domains.

PMID- 24934174
TI  - Transposable Element Insertion and Epigenetic Modification Cause the Multiallelic
      Variation in the Expression of FAE1 in Sinapis alba.
AB  - Naturally occurring heritable variation provides a fundamental resource to reveal
      the genetic and molecular bases of traits in forward genetic studies. Here, we
      report the molecular basis of the differences in the four alleles E1, E2, E3, and
      e of the FATTY ACID ELONGATION1 (FAE1) gene controlling high, medium, low, and
      zero erucic content in yellow mustard (Sinapis alba). E1 represents a fully
      functional allele with a coding DNA sequence (CDS) of 1521 bp and a promoter
      adjacent to the CDS. The null allele e resulted from an insertional disruption in
      the CDS by Sal-PIF, a 3100-bp PIF/Harbinger-like DNA transposon, whereas E2 and
      E3 originated from the insertion of Sal-T1, a 4863-bp Copia-like retrotransposon,
      in the 5' untranslated region. E3 was identical to E2 but showed cytosine
      methylation in the promoter region and was thus an epiallele having a further
      reduction in expression. The coding regions of E2 and E3 also contained five
      single-nucleotide polymorphisms (SNPs) not present in E1, but expression studies
      in Saccharomyces cerevisiae indicated that these SNPs did not affect enzyme
      functionality. These results demonstrate a comprehensive molecular framework for
      the interplay of transposon insertion, SNP/indel mutation, and epigenetic
      modification influencing the broad range of natural genetic variation in plants.

PMID- 24934175
TI  - NetworkViewer: visualizing biochemical reaction networks with embedded rendering
      of molecular interaction rules.
AB  - BACKGROUND: Network representations of cell-biological signaling processes
      frequently contain large numbers of interacting molecular and multi-molecular
      components that can exist in, and switch between, multiple biochemical and/or
      structural states. In addition, the interaction categories (associations,
      dissociations and transformations) in such networks cannot satisfactorily be
      mapped onto simple arrows connecting pairs of components since their
      specifications involve information such as reaction rates and conditions with
      regard to the states of the interacting components. This leads to the challenge
      of having to reconcile competing objectives: providing a high-level overview
      without omitting relevant information, and showing interaction specifics while
      not overwhelming users with too much detail displayed simultaneously. This
      problem is typically addressed by splitting the information required to
      understand a reaction network model into several categories that are rendered
      separately through combinations of visualizations and/or textual and tabular
      elements, requiring modelers to consult several sources to obtain comprehensive
      insights into the underlying assumptions of the model. RESULTS: We report the
      development of an application, the Simmune NetworkViewer, that visualizes
      biochemical reaction networks using iconographic representations of protein
      interactions and the conditions under which the interactions take place using the
      same symbols that were used to specify the underlying model with the Simmune
      Modeler. This approach not only provides a coherent model representation but,
      moreover, following the principle of "overview first, zoom and filter, then
      details-on-demand," can generate an overview visualization of the global network
      and, upon user request, presents more detailed views of local sub-networks and
      the underlying reaction rules for selected interactions. This visual integration
      of information would be difficult to achieve with static network representations
      or approaches that use scripted model specifications without offering simple but
      detailed symbolic representations of molecular interactions, their conditions and
      consequences in terms of biochemical modifications. CONCLUSIONS: The Simmune
      NetworkViewer provides concise, yet comprehensive visualizations of reaction
      networks created in the Simmune framework. In the near future, by adopting the
      upcoming SBML standard for encoding multi-component, multi-state molecular
      complexes and their interactions as input, the NetworkViewer will, moreover, be
      able to offer such visualization for any rule-based model that can be exported to
      that standard.

PMID- 24934176
TI  - Preoperative beta-blockade in coronary artery bypass grafting surgery.

PMID- 24934178
TI  - Liver X receptor beta is essential for the differentiation of radial glial cells
      to oligodendrocytes in the dorsal cortex.
AB  - Several psychiatric disorders are associated with aberrant white matter
      development, suggesting oligodendrocyte and myelin dysfunction in these diseases.
      There are indications that radial glial cells (RGCs) are involved in initiating
      myelination, and may contribute to the production of oligodendrocyte progenitor
      cells (OPCs) in the dorsal cortex. Liver X receptors (LXRs) are involved in
      maintaining normal myelin in the central nervous system (CNS), however, their
      function in oligodendrogenesis and myelination is not well understood. Here, we
      demonstrate that loss of LXRbeta function leads to abnormality in locomotor
      activity and exploratory behavior, signs of anxiety and hypomyelination in the
      corpus callosum and optic nerve, providing in vivo evidence that LXRbeta deletion
      delays both oligodendrocyte differentiation and maturation. Remarkably, along the
      germinal ventricular zone-subventricular zone and corpus callosum there is
      reduced OPC production from RGCs in LXRbeta(-/-) mice. Conversely, in cultured
      RGC an LXR agonist led to increased differentiation into OPCs. Collectively,
      these results suggest that LXRbeta, by driving RGCs to become OPCs in the dorsal
      cortex, is critical for white matter development and CNS myelination, and point
      to the involvement of LXRbeta in psychiatric disorders. 

PMID- 24934177
TI  - Adenomatous polyposis coli protein deletion leads to cognitive and autism-like
      disabilities.
AB  - Intellectual disabilities (IDs) and autism spectrum disorders link to human APC
      inactivating gene mutations. However, little is known about adenomatous polyposis
      coli's (APC's) role in the mammalian brain. This study is the first direct test
      of the impact of APC loss on central synapses, cognition and behavior. Using our
      newly generated APC conditional knock-out (cKO) mouse, we show that deletion of
      this single gene in forebrain neurons leads to a multisyndromic
      neurodevelopmental disorder. APC cKO mice, compared with wild-type littermates,
      exhibit learning and memory impairments, and autistic-like behaviors (increased
      repetitive behaviors, reduced social interest). To begin to elucidate neuronal
      changes caused by APC loss, we focused on the hippocampus, a key brain region for
      cognitive function. APC cKO mice display increased synaptic spine density, and
      altered synaptic function (increased frequency of miniature excitatory synaptic
      currents, modestly enhanced long-term potentiation). In addition, we found
      excessive beta-catenin levels and associated changes in canonical Wnt target gene
      expression and N-cadherin synaptic adhesion complexes, including reduced levels
      of presenilin1. Our findings identify some novel functional and molecular changes
      not observed previously in other genetic mutant mouse models of co-morbid
      cognitive and autistic-like disabilities. This work thereby has important
      implications for potential therapeutic targets and the impact of their
      modulation. We provide new insights into molecular perturbations and cell types
      that are relevant to human ID and autism. In addition, our data elucidate a novel
      role for APC in the mammalian brain as a hub that links to and regulates synaptic
      adhesion and signal transduction pathways critical for normal cognition and
      behavior. 

PMID- 24934179
TI  - Cytokine aberrations in autism spectrum disorder: a systematic review and meta
      analysis.
AB  - The role of non-diagnostic features in the pathophysiology of autism spectrum
      disorders (ASDs) is unclear. Increasing evidence suggests immune system
      alterations in ASD may be implicated in the severity of behavioral impairment and
      other developmental outcomes. The primary objective of this meta-analysis was to
      investigate if there is a characteristic abnormal cytokine profile in ASD
      compared with healthy controls (HCs). We identified relevant studies following a
      search of MEDLINE, EMBASE, PsycINFO, Web of Knowledge and Scopus. A meta-analysis
      was performed on studies comparing plasma and serum concentrations of cytokines
      in unmedicated participants with ASD and HCs. Results were reported according to
      PRISMA statement. Seventeen studies with a total sample size of 743 participants
      with ASD and 592 HC were included in the analysis. Nineteen cytokines were
      assessed. Concentrations of interleukin (IL)-1beta (P<0.001), IL-6 (P=0.03), IL-8
      (P=0.04), interferon-gamma (P=0.02), eotaxin (P=0.01) and monocyte chemotactic
      protein-1 (P<0.05) were significantly higher in the participants with ASD
      compared with the HC group, while concentrations of transforming growth factor
      beta1 were significantly lower (P<0.001). There were no significant differences
      between ASD participants and controls for the other 12 cytokines analyzed. The
      findings of our meta-analysis identified significantly altered concentrations of
      cytokines in ASD compared to HCs, strengthening evidence of an abnormal cytokine
      profile in ASD where inflammatory signals dominate. 

PMID- 24934180
TI  - Generating anatomical variation through mutations in networks - implications for
      evolution.
AB  - Genetic mutation leads to anatomical variation only indirectly because many
      proteins involved in generating anatomical structures in embryos operate
      cooperatively within molecular networks. These include gene-regulatory or control
      networks (CNs) for timing, signaling and patterning together with the process
      networks (PNs) for proliferation, apoptosis, differentiation and morphogenesis
      that they control. This paper argues that anatomical variation is achieved
      through a two-stage process: mutation alters the outputs of CNs and perhaps the
      proliferation network, and such changed outputs alter the ways that PNs construct
      tissues. This systems-biology approach has several implications: first, because
      networks contain many cooperating proteins, they amplify the effects of genetic
      variation so enabling mutation to generate a wider range of phenotypes than a
      single changed protein acting alone could. Second, this amplification helps
      explain how novel phenotypes can be produced relatively rapidly. Third, because
      even organisms with novel anatomical phenotypes derive from variants in standard
      networks, there is no genetic barrier to their producing viable offspring. This
      approach also clarifies a terminological difficulty: classical evolutionary
      genetics views genes in terms of phenotype heritability rather than as DNA
      sequences. This paper suggests that the molecular phenotype of the classical
      concept of a gene is often a protein network, with a mutation leading to an
      alteration in that network's dynamics. 

PMID- 24934181
TI  - Interventions for family members of adolescents with disruptive behavior
      disorders.
AB  - PROBLEM: The family members of adolescents diagnosed with disruptive behavior
      disorders (DBDs) experience profound stress and burden. Despite the need for
      empirically supported interventions that address the challenges faced by these
      family members, few such interventions are available. METHODS: In this
      qualitative descriptive study, we conducted in-depth interviews with 15 families
      of adolescents diagnosed with DBD. We asked the family members to identify what
      types of mental health services they needed and to describe the "ideal" program
      that would best address their concerns. FINDINGS: Family members identified
      several intervention modalities that would fit their needs, including multifamily
      groups, family therapy, individual therapy, and community-based hotlines. They
      indicated that programs should address the following topics: family
      communication, conflict resolution, education about DBD, and strategies to
      improve interactions with child service agencies. CONCLUSIONS: Clinicians should
      recognize that all family members may need support to manage the stressors
      associated with caring for or living with adolescents with DBD. When working with
      families, clinicians should provide information about the etiology and management
      of DBD, help navigate interactions with child service agencies, and employ
      strategies to improve family communication and functioning.

PMID- 24934183
TI  - Synthesis and catalytic application of PVP-coated Ru nanoparticles embedded in a
      porous metal-organic framework.
AB  - A hybrid catalyst consisting of polymer-coated Ru nanoparticles (Ru-PVP, PVP:
      poly(N-vinyl-2-pyrrolidone)) embedded in a porous metal-organic framework of ZIF
      8 (Ru-PVP@ZIF-8) was synthesized by the crystallization of ZIF-8 in a methanol
      solution of Ru-PVP. The structural properties of Ru-PVP@ZIF-8 were examined by N2
      gas adsorption, infrared spectra, and X-ray powder diffraction measurements. We
      successfully identified the most appropriate pretreatment conditions for surface
      activation of the Ru nanoparticles in the catalyst. The pretreated Ru-PVP@ZIF-8
      was applied for a CO oxidation reaction with H2 gas feeds. Ru-PVP@ZIF-8 was found
      to exhibit higher catalytic activities and higher CO2 selectivity than those
      observed on a carbon-supported Ru-PVP (Ru-PVP/C), implying that the pores of the
      ZIF-8 provide a more suitable environment for the reaction with O2 and CO gases. 

PMID- 24934182
TI  - CHRNA5 variants moderate the effect of nicotine deprivation on a neural index of
      cognitive control.
AB  - Individuals with reduced attention and memory cognitive control-related processes
      may be motivated to smoke as a result of the cognitive enhancing effects of
      nicotine. Further, nicotine deprivation-induced reductions in cognitive control
      may negatively reinforce smoking. Minor allele carriers at rs16969968 in the
      nicotinic acetylcholine receptor alpha5 subunit gene (CHRNA5) have been shown to
      exhibit both reduced cognitive control and greater nicotine dependence. It is
      therefore of interest to see if variants in this gene moderate the influence of
      nicotine deprivation on cognitive control. P3b and P3a components of the event
      related brain potential waveform evoked by a three-stimulus visual oddball task
      are widely viewed as positive indices of cognitive control-related processes. We
      tested the hypothesis that individuals possessing at least one minor allele at
      rs16969968 in CHRNA5 would show greater nicotine deprivation-induced reductions
      in P3b and P3a amplitude. The sample included 72 non-Hispanic, Caucasian heavy
      smokers (54 men and 18 women) with a mean age of 36.11 years (SD = 11.57).
      Participants completed the visual oddball task during counterbalanced nicotine
      and placebo smoking sessions. Findings indicated that rs16969968 status did not
      moderate nicotine effects on P3b or P3a, whereas variation in other CHRNA5
      polymorphisms, which are not as well characterized and are not in linkage
      disequilibrium with rs16969968, predicted nicotine deprivation-induced reduction
      of P3a amplitude: rs588765 (F1,68 = 7.74, P = 0.007) and rs17408276 (F1,67 =
      7.34, P = 0.009). Findings are interpreted in the context of vulnerability
      alleles that may predict nicotine effects on cognitive control. 

PMID- 24934184
TI  - Drug repurposing based on drug-drug interaction.
AB  - Given the high risk and lengthy procedure of traditional drug development, drug
      repurposing is gaining more and more attention. Although many types of drug
      information have been used to repurpose drugs, drug-drug interaction data, which
      imply possible physiological effects or targets of drugs, remain unexploited. In
      this work, similarity of drug interaction was employed to infer similarity of the
      physiological effects or targets for the drugs. We collected 10,835 drug-drug
      interactions concerning 1074 drugs, and for 700 of them, drug similarity scores
      based on drug interaction profiles were computed and rendered using a drug
      association network with 589 nodes (drugs) and 2375 edges (drug similarity
      scores). The 589 drugs were clustered into 98 groups with Markov Clustering
      Algorithm, most of which were significantly correlated with certain drug
      functions. This indicates that the network can be used to infer the physiological
      effects of drugs. Furthermore, we evaluated the ability of this drug association
      network to predict drug targets. The results show that the method is effective
      for 317 of 561 drugs that have known targets. Comparison of this method with the
      structure-based approach shows that they are complementary. In summary, this
      study demonstrates the feasibility of drug repurposing based on drug-drug
      interaction data.

PMID- 24934186
TI  - Interview with Martina Stenzel.

PMID- 24934185
TI  - An investigation of Candida species isolated from blood cultures during 17 years
      in a university hospital.
AB  - Candidemia is the most frequent manifestation observed with invasive candidiasis.
      The aim of this study was to analyse the trends of candidemia in a large tertiary
      care hospital to determine the overall incidence during January 1996-December
      2012, as well as to determine the susceptibility of 453 isolates according to the
      revised Clinical and Laboratory Standards Institute (CLSI) breakpoints.
      Candidemia episodes in adult and paediatric patients were retrospectively
      analysed from the laboratory data of Uludag University Healthcare and Research
      Hospital. The 17-year period studied was divided into three periods (1996-2001,
      2002-2007 and 2008-2012) for better comparison, and candidemia incidence was
      determined by the ratio of total number of patients with candidemia per 1000
      patients admitted to the hospital and per 10 000 patient days in these three
      periods. Redefined CLSI M27-A3 breakpoints were used for interpretation of
      antifungal susceptibility results. Candidemia incidence was determined as 2.2,
      1.7 and 1.5 per 1000 admitted patients during 1996-2001, 2002-2007 and 2008-2012
      respectively. A significantly decreased candidemia incidence was obtained in the
      third period. C. albicans (43.8%) was the most common candidemia agent, followed
      by C.parapsilosis (26.5%) in all three periods. According to the revised CLSI
      breakpoints, there was fluconazole resistance in C. albicans, C.parapsilosis,
      C.tropicalis and C.glabrata species (1.4%, 18.2%, 2.6% and 14.3% respectively).
      Almost all Candida species were found susceptible to voriconazole except one
      C.glabrata (7.1%) isolate. Candidemia is an important health problem. Local
      epidemiological data are determinative in the choice of appropriate antifungal
      treatment agents.

PMID- 24934187
TI  - Comparative gene expression analyses reveal heterochrony for Sox9 expression in
      the cranial neural crest during marsupial development.
AB  - Compared to placental mammals, marsupials have short gestation period, and their
      neonates are relatively immature. Despite these features, marsupial neonates must
      travel from the birth canal to the teat, suckle and digest milk to complete
      development. Thus, certain organs and tissues of marsupial neonates, such as
      forelimbs to crawl and jaw elements to suckle, must develop early. Previous
      reports showed that cranial neural crest (CNC) cells, as the source of
      ectomesenchyme of jaw elements, are generated significantly early in gray short
      tailed opossum (Monodelphis domestica) compared to other amniote models, such as
      mouse. In this study, we examined the expression of genes known to be important
      for neural crest formation, such as BMP2/BMP4 (neural crest inducer), Pax7
      (neural border specifier), Snail1 and Sox9/Sox10 (neural crest specifier) in
      Monodelphis domestica, and compared the expression patterns with those in mouse,
      chicken, and gecko embryos. Among those genes, the expression of Sox9 was turned
      on early and broadly in the premigratory CNC cells, and persisted in the
      ectomesenchyme of the cranial anlagen in opossum embryos. In contrast, Sox9
      expression diminished in the CNC cells of other animals at the early phase of
      migration. Comparison of the onset of Pax7 and Sox9 expression revealed that Sox9
      expression in the prospective CNC was earlier and broader than Pax7 expression in
      opossum, suggesting that the sequence of border specification and neural crest
      specification is altered. This study provides the first clue for understanding
      the molecular basis for the heterochronic development of the CNC cells and jaw
      elements in marsupials. 

PMID- 24934188
TI  - Connective tissue diseases: Epstein-Barr virus in Sjogren's syndrome salivary
      glands drives local autoimmunity.

PMID- 24934190
TI  - Rheumatoid arthritis: Who knows why regulatory T cells are defective in RA ...
      IDO.

PMID- 24934189
TI  - Vasculitis: determinants of disease patterns.
AB  - The vasculitides are a large group of heterogeneous diseases for which it has
      been assumed that pathogenesis is largely autoimmune. As clinicians, we
      distinguish one form of vasculitis from another on the basis of observed patterns
      of organ injury, the size of the vessels affected and histopathological findings.
      The terms 'small-vessel', 'medium-vessel' and 'large-vessel' vasculitis are
      useful clinical descriptors, but fail to inform us about why vessels of a certain
      calibre are favoured by one disease and not another. Classification based on
      vessel size also fails to consider that vessels of a specific calibre are not
      equally prone to injury. Distinct vulnerabilities undoubtedly relate to the fact
      that same-size vessels in different tissues may not be identical conduits. In
      fact, vessels become specialized, from the earliest stages of embryonic
      development, to suit the needs of different anatomical locations. Vessels of the
      same calibre in different locations and organs are as different as the organ
      parenchymal cells through which they travel. The dialogue between developing
      vessels and the tissues they perfuse is designed to meet special local needs.
      Added to the story of vascular diversity and vulnerability are changes that occur
      during growth, development and ageing. An improved understanding of the unique
      territorial vulnerabilities of vessels could form the basis of new hypotheses for
      the aetiopathogenesis of the vasculitides. This Review considers how certain
      antigens, including infectious agents, might become disease-relevant and how
      vascular diversity could influence disease phenotypes and the spectrum of
      vascular inflammatory diseases. 

PMID- 24934192
TI  - Autoimmunity: regulatory B cells--IL-35 and IL-21 regulate the regulators.
AB  - IL-21 regulates the activity and number of IL-10-producing regulatory B cells
      (B10 cells) that modulate immune responses and limit diverse autoimmune diseases.
      A new study demonstrates that IL-35 has a similar function. Identifying
      regulatory circuits that control B10-cell function in vivo might open the door to
      future treatments for autoimmune diseases.

PMID- 24934191
TI  - Defining populations at risk of rheumatoid arthritis: the first steps to
      prevention.
AB  - Preventing disease is a public health priority. In recent years, this focus has
      evolved to include noncommunicable chronic diseases such as cardiovascular
      disease and diabetes mellitus but is novel in rheumatic diseases such as
      rheumatoid arthritis (RA). In order to prevent RA, the 'at-risk' populations need
      to be defined. To date, a number of studies have attempted to clarify our
      understanding of these cohorts and how they could be identified. Suggested
      terminology has now been published to define individuals who might go on to
      develop RA. This Review considers categories of these 'at-risk' individuals, with
      a focus on those with systemic autoimmunity. Trials in very early RA demonstrate
      that disease outcomes can be reduced with early intervention. These principles
      are widely accepted in other diseases such as type 1 diabetes mellitus, in which
      steps have been taken to prevent disease in genetically predisposed individuals.
      Large population-based studies provide insights into potential interventions for
      RA prevention. By quantifying risk in different populations, the prospect of
      preventing this disease is feasible. 

PMID- 24934194
TI  - Value analysis of neodymium content in shredder feed: toward enabling the
      feasibility of rare earth magnet recycling.
AB  - In order to facilitate the development of recycling technologies for rare earth
      magnets from postconsumer products, we present herein an analysis of the
      neodymium (Nd) content in shredder scrap. This waste stream has been chosen on
      the basis of current business practices for the recycling of steel, aluminum, and
      copper from cars and household appliances, which contain significant amounts of
      rare earth magnets. Using approximations based on literature data, we have
      calculated the average Nd content in the ferrous shredder product stream to be
      between 0.13 and 0.29 kg per ton of ferrous scrap. A value analysis considering
      rare earth metal prices between 2002 and 2013 provides values between $1.32 and
      $145 per ton of ferrous scrap for this material, if recoverable as pure Nd metal.
      Furthermore, we present an analysis of the content and value of other rare earths
      (Pr, Dy, Tb). 

PMID- 24934193
TI  - Nicotine withdrawal and stress-induced changes in pain sensitivity: a cross
      sectional investigation between abstinent smokers and nonsmokers.
AB  - Chronic smoking has been linked with alterations in endogenous pain regulation.
      These alterations may be pronounced when individuals quit smoking because
      nicotine withdrawal produces a variety of psychological and physiological
      symptoms. Smokers interested in quitting (n = 98) and nonsmokers (n = 37)
      completed a laboratory session including cold pressor test (CPT) and heat thermal
      pain. Smokers set a quit date and completed the session after 48 h of abstinence.
      Participants completed the pain assessments once after rest and once after
      stress. Cardiovascular and nicotine withdrawal measures were collected. Smokers
      showed blunted cardiovascular responses to stress relative to nonsmokers. Only
      nonsmokers had greater pain tolerance to CPT after stress than after rest. Lower
      systolic blood pressure was related to lower pain tolerance. These findings
      suggest that smoking withdrawal is associated with blunted stress response and
      increased pain sensitivity.

PMID- 24934195
TI  - Percutaneous cholecystostomy for acute cholecystitis: who should really benefit
      from this procedure?

PMID- 24934196
TI  - Percutaneous cholecystostomy for acute cholecystitis: who should really benefit
      from this procedure?

PMID- 24934197
TI  - Evaluation of stapler hepatectomy in laparoscopic liver resection.

PMID- 24934201
TI  - Factors affecting the volumetric energy density of lithium-ion battery materials:
      particle density measurements and cross-sectional observations of layered LiCo(1
      x)Ni(x)O2 with 0 <= x <= 1.
AB  - Volumetric capacity Qvol (mAh cm(-3)), more correctly, volumetric energy density
      Wvol (mWh cm(-3)), is a crucial property of lithium-ion battery (LIB) materials,
      because LIBs are devices that operate in a limited space. The actual value of
      Wvol (Wvol(act)) is currently limited to 40-60% of the maximum (theoretical)
      value of Wvol (Wvol(max)), for reasons that have not yet been fully clarified.
      Thus, to gain information that will enable an increase in Wvol(act) such that it
      is closer to Wvol(max), systematic studies of the values for Qvol, Wvol, true
      density (dXRD), and particle density (dp) obtained using gas pycnometry were
      undertaken for LiCo1-xNixO2 samples with 0 <= x <= 1. Here, dp is the density
      that includes the volume of the closed pores in the particles, and consequently
      is less than dXRD, which is determined by X-ray diffraction (XRD) measurement.
      DXRD monotonically decreased from 5.062(1) g cm(-3) for x = 0 to 4.779(1) g cm(
      3) for x = 1, as expected. On the contrary, dp decreased almost linearly from
      4.98(2) g cm(-3) for x = 0 to 4.80(2) g cm(-3) for x = 0.5, then suddenly dropped
      to 4.63(2) g cm(-3) for x = 0.667, and finally leveled off to a constant value
      (~4.6 g cm(-3)) at larger values of x. The cross-sectional observations using a
      Focused Ion Beam system revealed that the significantly smaller values for dp
      compared with those for dXRD, particularly when x > 0.5, is due to the presence
      of closed pores in agglomerated secondary particles. This indicates that the
      closed pores in the secondary particles play an important role in determining the
      value of Wvol(act) for LIBs. The formation of well-developed primary particles as
      a mean for increasing the value of dp was also investigated.

PMID- 24934200
TI  - Prospectively assessed clinical outcomes in concussive blast vs nonblast
      traumatic brain injury among evacuated US military personnel.
AB  - IMPORTANCE: Blast injury has been identified as the signature injury in the
      conflicts in Iraq and Afghanistan. However it remains to be determined whether
      fundamental differences may exist between blast-related traumatic brain injury
      (TBI) and TBI due to other mechanisms. OBJECTIVES: To determine similarities and
      differences between clinical outcomes in US military personnel with blast-related
      vs. non-blast-related concussive TBI and to identify the specific domains of
      impairment that best correlate with overall disability. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective cohort study involving active duty US Military
      personnel evacuated from Iraq or Afghanistan to Landstuhl Regional Medical
      Center, in Landstuhl, Germany. Four groups of participants were enrolled from
      2010 to 2013: (1) blast plus impact complex TBI (n=53), (2) non-blast related TBI
      with injury due to other mechanisms (n=29), (3) blast-exposed controls evacuated
      for other medical reasons (n=27) (4) non-blast-exposed controls evacuated for
      other medical reasons (n=69). All patients with TBI met Department of Defense
      criteria for concussive (mild) TBI. The study participants were evaluated 6-12
      months after injury at Washington University in St Louis. In total, 255 subjects
      were enrolled in the study, and 183 participated in follow-up evaluations, 5 of
      whom were disqualified. MAIN OUTCOMES AND MEASURES: In-person clinical
      examinations included evaluation for overall disability, a standardized
      neurological exam, headache questionnaires, neuropsychological test battery,
      combat exposure and alcohol use surveys, and structured interview evaluations for
      post-traumatic stress disorder (PTSD) and depression. RESULTS: Global outcomes,
      headache severity, neuropsychological performance, and surprisingly even PTSD
      severity and depression were indistinguishable between the two TBI groups,
      independent of mechanism of injury. Both TBI groups had higher rates of moderate
      to severe overall disability than the respective control groups: 41/53 (77%) of
      blast plus impact TBI and 23/29 (79%) of nonblast TBI vs. 16/27 (59%) of blast
      exposed controls and 28/69 (41%) of non-blast-exposed controls. In addition,
      blast-exposed controls had worse headaches and more severe PTSD than non-blast
      exposed controls. Self-reported combat exposure intensity was higher in the blast
      plus impact TBI group than in nonblast TBI group and was higher in blast-exposed
      controls than in non-blast-exposed controls. However, combat exposure intensity
      did not correlate with PTSD severity in the TBI groups, but a modest positive
      correlation was observed in the controls. Overall outcomes were most strongly
      correlated with depression, headache severity, and number of abnormalities on
      neuropsychological testing. However a substantial fraction of the variance in
      overall outcome was not explained by any of the assessed measures. CONCLUSIONS
      AND RELEVANCE: One potential interpretation of these results is that TBI itself,
      independent of injury mechanism and combat exposure intensity, is a primary
      driver of adverse outcomes. Many other important factors may be as yet
      unmeasured, and adverse outcomes following war-time injuries are difficult to
      fully explain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01313130.

PMID- 24934202
TI  - The single-site Green's function and Krein's theorem.
AB  - An important step in electronic structure calculations using multiple-scattering
      theory is obtaining the density of states for the central site from the Green's
      function for that site. We have found that the Krein's spectral displacement
      function for the central site contributes significantly to the understanding of
      these calculations. We argue that these insights can lead to improvements in the
      robustness of MST electronic structure codes without negatively impacting their
      performance. 

PMID- 24934203
TI  - Canine rabies in Australia: a review of preparedness and research needs.
AB  - Australia is unique as a populated continent in that canine rabies is exotic,
      with only one likely incursion in 1867. This is despite the presence of a
      widespread free-ranging dog population, which includes the naturalized dingo,
      feral domestic dogs and dingo-dog cross-breeds. To Australia's immediate north,
      rabies has recently spread within the Indonesian archipelago, with outbreaks
      occurring in historically free islands to the east including Bali, Flores, Ambon
      and the Tanimbar Islands. Australia depends on strict quarantine protocols to
      prevent importation of a rabid animal, but the risk of illegal animal movements
      by fishing and recreational vessels circumventing quarantine remains. Predicting
      where rabies will enter Australia is important, but understanding dog population
      dynamics and interactions, including contact rates in and around human
      populations, is essential for rabies preparedness. The interactions among and
      between Australia's large populations of wild, free-roaming and restrained
      domestic dogs require quantification for rabies incursions to be detected and
      controlled. The imminent risk of rabies breaching Australian borders makes the
      development of disease spread models that will assist in the deployment of cost
      effective surveillance, improve preventive strategies and guide disease
      management protocols vitally important. Here, we critically review Australia's
      preparedness for rabies, discuss prevailing assumptions and models, identify
      knowledge deficits in free-roaming dog ecology relating to rabies maintenance and
      speculate on the likely consequences of endemic rabies for Australia. 

PMID- 24934205
TI  - Postural tachycardia syndrome is associated with significant symptoms and
      functional impairment predominantly affecting young women: a UK perspective.
AB  - OBJECTIVE: To examine a large UK cohort of patients with postural tachycardia
      syndrome (PoTS), to compare demographic characteristics, symptoms and treatment
      of PoTS at one centre compared to the largest patient group PoTS UK and to verify
      if their functional limitation is similar to patients with chronic fatigue
      syndrome (CFS). DESIGN: A cross-sectional study assessed the frequency of
      symptoms and their associated variables. PATIENTS AND SETTING: Two PoTS cohorts
      were: (1) recruited via PoTS UK, (2) diagnosed at Newcastle Hospitals National
      Health Service (NHS) Foundation Trust 2009-2012. Patients with PoTS were then
      compared to a matched cohort with CFS. MAIN OUTCOME MEASURES: Patients' detailed
      demographics, time to diagnosis, education, disability, medications, comorbidity
      and precipitants. Symptom assessment tools captured, Fatigue Impact Scale,
      Epworth Sleepiness Scale, Orthostatic Grading Scale (OGS), Hospital Anxiety and
      Depression Scale, Health Assessment Questionnaire, Cognitive Failures
      Questionnaire. RESULTS: 136 patients with PoTS participated (84 members of PoTS
      UK (170 cohort; 50% return) and 52 (87 cohort; 60%) from Newcastle Clinics). The
      PoTS UK population was significantly younger than the clinic patients, with
      significantly fewer men (p=0.005). Over 60% had a university or postgraduate
      degree. Significantly more of the PoTS UK cohort were working, with hours worked
      being significantly higher (p=0.001). Time to diagnosis was significantly longer
      in the PoTS UK cohort (p=0.04). Symptom severity was comparable between cohorts.
      The PoTS total group was compared with a matched CFS cohort; despite comparable
      levels of fatigue and sleepiness, autonomic symptom burden (OGS) was
      statistically significantly higher. The most common treatment regime included
      beta-blockers. Overall, 21 treatment combinations were described. Up to 1/3 were
      taking no treatment. CONCLUSIONS: Patients with PoTS are predominantly women,
      young, well educated and have significant and debilitating symptoms that impact
      significantly on quality of life. Despite this, there is no consistent treatment.

PMID- 24934207
TI  - Multiparametric MRI followed by targeted prostate biopsy for men with suspected
      prostate cancer: a clinical decision analysis.
AB  - OBJECTIVE: To compare the diagnostic outcomes of the current approach of
      transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer
      to an alternative approach using multiparametric MRI (mpMRI), followed by MRI
      targeted biopsy if positive. DESIGN: Clinical decision analysis was used to
      synthesise data from recently emerging evidence in a format that is relevant for
      clinical decision making. POPULATION: A hypothetical cohort of 1000 men with
      suspected prostate cancer. INTERVENTIONS: mpMRI and, if positive, MRI-targeted
      biopsy compared with TRUS-guided biopsy in all men. OUTCOME MEASURES: We report
      the number of men expected to undergo a biopsy as well as the numbers of
      correctly identified patients with or without prostate cancer. A probabilistic
      sensitivity analysis was carried out using Monte Carlo simulation to explore the
      impact of statistical uncertainty in the diagnostic parameters. RESULTS: In 1000
      men, mpMRI followed by MRI-targeted biopsy 'clinically dominates' TRUS-guided
      biopsy as it results in fewer expected biopsies (600 vs 1000), more men being
      correctly identified as having clinically significant cancer (320 vs 250), and
      fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated
      TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity
      analysis. CONCLUSIONS: Our analysis suggests that mpMRI followed by MRI-targeted
      biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy.
      Future research in prostate cancer should focus on providing precise estimates of
      key diagnostic parameters.

PMID- 24934208
TI  - What keeps family physicians busy in Portugal? A multicentre observational study
      of work other than direct patient contacts.
AB  - OBJECTIVES: To quantify the time spent by family physicians (FP) on tasks other
      than direct patient contact, to evaluate job satisfaction, to analyse the
      association between time spent on tasks and physician characteristics, the
      association between the number of tasks performed and physician characteristics
      and the association between time spent on tasks and job satisfaction. DESIGN:
      Cross-sectional, using time-and-motion techniques. Two workdays were documented
      by direct observation. A significance level of 0.05 was adopted. SETTING:
      Multicentric in 104 Portuguese family practices. PARTICIPANTS: A convenience
      sample of FP, with lists of over 1000 patients, teaching senior medical students
      and first-year family medicine residents in 2012, was obtained. Of the 217 FP
      invited to participate, 155 completed the study. MAIN OUTCOMES MEASURED: Time
      spent on tasks other than direct patient contact and on the performance of more
      than one task simultaneously, the number of direct patient contacts in the
      office, the number of indirect patient contacts, job satisfaction, demographic
      and professional characteristics associated with time spent on tasks and the
      number of different tasks performed, and the association between time spent on
      tasks and job satisfaction. RESULTS: FP (n=155) spent a mean of 143.6 min/day
      (95% CI 135.2 to 152.0) performing tasks such as prescription refills, teaching,
      meetings, management and communication with other professionals (33.4% of their
      workload). FP with larger patient lists spent less time on these tasks (p=0.002).
      Older FP (p=0.021) and those with larger lists (p=0.011) performed fewer tasks.
      The mean job satisfaction score was 3.5 (out of 5). No association was found
      between job satisfaction and time spent on tasks. CONCLUSIONS: FP spent one-third
      of their workday in coordinating care, teaching and managing. Time devoted to
      these tasks decreases with increasing list size and physician age.

PMID- 24934211
TI  - Low incidence of late pseudoaneurysm and reoperation after conventional repair of
      acute type a aortic dissection.
AB  - BACKGROUND AND AIM: Suture line dehiscence and pseudoaneurysm formation is one of
      the leading causes of late reoperation after surgical repair of acute type A
      aortic dissection (AAD). A sandwich technique can affect the need of reoperation.
      We sought to assess the late outcomes (mortality and reoperation) of a modified
      reinforced sandwich technique in conventional AAD repair. METHODS: Retrospective
      review of 63 consecutive patients undergoing AAD repair between 2003 and 2013.
      Aortic anastomosis was performed with a modified reinforced sandwich technique
      using Hemashield strips and two-layer polypropylene continuous and interrupted
      mattress sutures. RESULTS: Marfan syndrome was diagnosed in five (8%) and
      bicuspid aortic valve in three patients (5%). Twenty-one patients (33%) had
      preoperative cardiogenic shock necessitating inotropic support. Replacement of
      the ascending aorta with aortic valve preservation was performed in 58 (92%) and
      hemiarch replacement in five patients (8%). Four patients died during initial
      hospitalization, yielding a hospital mortality of 6%. Median follow-up duration
      was 73 months (range, 1-124). Kaplan-Meier survival rates were 94 +/- 3%, 84 +/-
      5%, and 59 +/- 11% at 1, 5, and 10 years. One patient (1.7%) required proximal
      reoperation 44 months after AAD repair because of progressive dilatation of the
      aortic root. No patient had severe aortic regurgitation or pseudoaneurysm after
      AAD repair. Actuarial freedom from reoperation at 1, 5, and 10 years was 100%,
      97%, and 97%. CONCLUSIONS: A reinforced sandwich technique was a good technique
      resulting in a low incidence of late reoperation and pseudoaneurysm formation.

PMID- 24934210
TI  - Participation in physical activity in patients 1-4 years post total joint
      replacement in the Dominican Republic.
AB  - BACKGROUND: To address both the growing burden of joint disease and the gaps in
      medical access in developing nations, medical relief organizations have begun to
      launch programs to perform total joint replacement (TJR) on resident populations
      in developing countries. One outcome of TJR of particular interest is physical
      activity (PA) since it is strongly linked to general health. This study evaluates
      the amount of postoperative participation in PA in low-income patients who
      received total joint replacement in the Dominican Republic and identifies
      preoperative predictors of postoperative PA level. METHODS: We used the Yale
      Physical Activity Survey (YPAS) to assess participation in postoperative PA 1-4
      years following total knee or hip replacement. We compared the amount of aerobic
      PA reported by postoperative TJR patients with the levels of PA recommended by
      the CDC and WHO. We also analyzed preoperative determinants of postoperative
      participation in aerobic PA in bivariate and multivariate analyses. RESULTS: 64
      patients out of 170 eligible subjects (52/128 TKR and 14/42 THR) who received TJR
      between 2009-2012 returned for an annual follow-up visit in 2013, with a mean
      treatment-to-follow-up time of 2.1 years. 43.3% of respondents met CDC/WHO
      criteria for sufficient participation in aerobic PA. Multivariate analyses
      including data from 56 individuals identified that patients who were both younger
      than 65 and at least two years postoperative had an adjusted mean activity
      dimensions summary index (ADSI) 22.9 points higher than patients who were 65 or
      older and one year postoperative. Patients who lived with friends or family had
      adjusted mean ADSI 17.2 points higher than patients living alone. Patients who
      had the most optimistic preoperative expectations of outcome had adjusted mean
      ADSI scores that were 19.8 points higher than those who were less optimistic.
      CONCLUSION: The TJR patients in the Dominican cohort participate in less PA than
      recommended by the CDC/WHO. Additionally, several associations were identified
      that potentially affect PA in this population; specifically, participants who are
      older than 65, recently postoperative, less optimistic about postoperative
      outcomes and who live alone participate in less PA.

PMID- 24934212
TI  - The cost of data collection for performance monitoring in hospitals: protocol for
      a systematic review.
AB  - BACKGROUND: Key performance indicators (KPIs) are used to identify where
      organisational performance is meeting desired standards and where performance
      requires improvement. Valid and reliable KPIs depend on the availability of high
      quality data, specifically, the relevant minimum data set (MDS; the core data
      identified as the minimum required to measure performance for a KPI) elements.
      However, the feasibility of collecting the relevant MDS elements is always a
      limitation of performance monitoring using KPIs. Preferably, data should be
      integrated into service delivery, and where additional data are required that are
      not currently collected as part of routine service delivery, there should be an
      economic evaluation to determine the cost of data collection. The aim of this
      systematic review is to synthesise the evidence base concerning the costs of data
      collection in hospitals for performance monitoring using KPIs, and to identify
      hospital data collection systems that have proven to be cost minimising.
      METHODS/DESIGN: Electronic databases will be systematically searched for
      publications in English that examine the cost of data collection within a
      hospital context. The database searches will be supplemented by searching through
      citations and references. Screening of both titles and abstracts will be done by
      two independent reviewers. All disagreements will be resolved by an independent
      third reviewer. Data analysis will be completed and reported in a narrative
      review. DISCUSSION: This review will cohere the evidence base regarding cost
      minimising hospital data collections systems for performance monitoring and if
      these are associated with potential benefits for patients. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42014007450.

PMID- 24934213
TI  - Evaluation of stresses developed in different bracket-cement-enamel systems using
      finite element analysis with in vitro bond strength tests.
AB  - BACKGROUND: The purpose of this study was to determine the bond strength of
      different orthodontic bracket materials (ceramic, stainless steel, and titanium)
      as well as stresses developed in bracket-cement-enamel systems using finite
      element (FE) analysis. METHODS: One hundred and thirty-five extracted human
      caries-free upper central incisors were divided into three groups (n = 45/group)
      according to the type of orthodontic bracket materials (stainless steel, ceramic,
      and titanium). Each group was further subdivided into three subgroups (n =
      15/group) according to the bond strength test loading mode (shear short side,
      shear long side, and tensile). After debonding, the fractured specimen was
      examined, and the adhesive remnant index (ARI) was determined. FE analysis models
      analyzed the stress distribution within the cement and enamel. Bond strengths
      were analyzed using ANOVA and Tukey's test, and the ARI scores were analyzed
      using chi-square (chi2) test. RESULTS: Shear loading at the short side of the
      bracket resulted in the highest bond strength and lowest maximum principal stress
      both on cement and enamel compared with the other loading modes (P < 0.05).
      Ceramic brackets presented with higher bond strength and lower maximum principal
      stress than metallic brackets (P < 0.05). There was a significant difference for
      ARI scores between the type of brackets (chi2 = 64.852, P < 0.001). CONCLUSION:
      The findings suggest that the manner of loading orthodontic brackets and the
      selection of orthodontic bracket materials affect the bond strength and stresses
      developed both on cement and enamel.

PMID- 24934214
TI  - The impact of context relevance during extinction learning.
AB  - In two predictive-learning experiments, we investigated the role of the
      informational value of contexts for the formation of context-specific extinction
      learning. The contexts were each composed of two elements from two dimensions, A
      and B. In Phase 1 of each experiment, participants received acquisition training
      with a target cue Z in context A1B1 (the numbers assign particular values on the
      context dimensions). In Phase 2, participants were trained with conditional
      discriminations between two other cues, X and Y, for which only one of the two
      context dimensions was relevant. In a third phase, participants received
      extinction trials with cue Z in context A2B2. During a final test phase, we
      observed that a partial change of the extinction context disrupted extinction
      performance when the extinction context was changed on the dimension that had
      been trained as being relevant for the conditional discrimination. However, when
      the extinction context was changed on the irrelevant context dimension,
      extinction performance was not affected. Our results are consistent with the idea
      that relevant contexts receive more attention than do irrelevant contexts,
      leading to stronger context-specific processing of information learned in the
      former than in the latter type of contexts. 

PMID- 24934215
TI  - Interventions aimed at increasing the level of physical activity by including
      organised follow-up: a systematic review of effect.
AB  - BACKGROUND: Organised follow-up is a common feature of several strategies at the
      primary health care level to promote health behaviour change, e.g. to increase
      physical activity. In Norway, municipal 'healthy living' centres run by health
      care personnel are established to offer counselling and organised follow-up of
      health behaviour change during a 12-week programme. We report the results of a
      systematic review commissioned by the Norwegian Directorate of Health concerning
      organised follow-up to improve physical activity. METHODS: We searched ten
      electronic databases up to June 2012, reference lists of included publications,
      and relevant journals. Study selection and quality risk of bias assessment were
      carried out independently. Data were synthesised narratively due to heterogeneity
      of measurements of physical activity. The GRADE approach was used to assess our
      confidence in the effect estimate for each outcome in each comparison. RESULTS:
      Fourteen randomised controlled trials from seven countries and with a total of
      5,002 participants were included in the systematic review. All studies were
      carried out in primary care or community settings. The interventions comprised
      referral to supervised group physical activity (2 studies), referral to local
      resources with follow-up (6 studies), and self-organised physical activity with
      follow-up (6 studies). The narrative synthesis, comprising a total of 39
      comparisons, indicated effects of self-organised physical activity with follow-up
      (compared to both advice and no treatment) and referral to local resources with
      follow-up (compared to advice) in some of the comparisons where we rated our
      confidence in the effect estimates as moderate. However, the results indicated no
      difference between intervention and control groups for the majority of
      comparisons. Follow-up in the studies was mainly short-term with the longest
      follow-up 9 months post-treatment. We rated our confidence in the effect
      estimates as low or very low in most comparisons, both for positive and neutral
      results. CONCLUSIONS: The results of this systematic review indicate considerable
      uncertainty concerning effects of organised follow-up during 10-14 weeks on
      physical activity. Major methodological problems concerning the measurement of
      physical activity are discussed. TRIAL REGISTRATION: Systematic review
      registration: PROSPERO CRD42011001598.

PMID- 24934216
TI  - Anti-inflammatory loaded poly-lactic glycolic acid nanoparticle formulations to
      enhance myocardial gene transfer: an in-vitro assessment of a drug/gene
      combination therapeutic approach for direct injection.
AB  - BACKGROUND: Cardiac gene therapy for heart disease is a major translational
      research area with potential, yet problems with safe and efficient gene transfer
      into cardiac muscle remain unresolved. Existing methodology to increase vector
      uptake include modifying the viral vector, non-viral particle encapsulation and
      or delivery with device systems. These advanced methods have made improvements,
      however fail to address the key problem of inflammation in the myocardium, which
      is known to reduce vector uptake and contribute to immunogenic adverse events.
      Here we propose an alternative method to co-deliver anti-inflammatory drugs in a
      controlled release polymer with gene product to improve therapeutic effects.
      METHODS: A robust, double emulsion production process was developed to
      encapsulate drugs into nanoparticles. Briefly in this proof of concept study,
      aspirin and prednisolone anti-inflammatory drugs were encapsulated in various
      poly-lactic glycolic acid polymer (PLGA) formulations. The resultant particle
      systems were characterized, co-delivered with GFP plasmid, and evaluated in
      harvested myocytes in culture for uptake. RESULTS: High quality nanoparticles
      were harvested from multiple production runs, with an average 64 +/- 10 mg yield.
      Four distinct particle drug system combinations were characterized and evaluated
      in vitro: PLGA(50:50) Aspirin, PLGA(65:35) Prednisolone, PLGA(65:35) Aspirin and
      PLGA(50:50) Prednisolone Particles consisted of spherical shape with a narrow
      size distribution 265 +/- 104 nm as found in scanning electron microscopy
      imaging. Prednisolone particles regardless of PLGA type were found on average ~
      100 nm smaller than the aspirin types. All four groups demonstrated high zeta
      potential stability and re-constitution testing prior to in vitro. In vitro
      results demonstrated co uptake of GFP plasmid (green) and drug loaded particles
      (red) in culture with no incidence of toxicity. CONCLUSIONS: Nano formulated anti
      inflammatories in combination with standalone gene product therapy may offer a
      clinical solution to maximize cardiac gene therapy product effects while
      minimizing the risk of the host response in the inflammatory myocardial
      environment.

PMID- 24934218
TI  - Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF)
      scores generated from the MMPI-2 and MMPI-2-RF test booklets: internal structure
      comparability in a sample of criminal defendants.
AB  - We investigated the internal structure comparability of Minnesota Multiphasic
      Personality Inventory-2-Restructured Form (MMPI-2-RF) scores derived from the
      MMPI-2 and MMPI-2-RF booklets in a sample of 320 criminal defendants (229 males
      and 54 females). After exclusion of invalid protocols, the final sample consisted
      of 96 defendants who were administered the MMPI-2-RF booklet and 83 who completed
      the MMPI-2. No statistically significant differences in MMPI-2-RF invalidity
      rates were observed between the two forms. Individuals in the final sample who
      completed the MMPI-2-RF did not statistically differ on demographics or referral
      question from those who were administered the MMPI-2 booklet. Independent t tests
      showed no statistically significant differences between MMPI-2-RF scores
      generated with the MMPI-2 and MMPI-2-RF booklets on the test's substantive
      scales. Statistically significant small differences were observed on the revised
      Variable Response Inconsistency (VRIN-r) and True Response Inconsistency (TRIN-r)
      scales. Cronbach's alpha and standard errors of measurement were approximately
      equal between the booklets for all MMPI-2-RF scales. Finally, MMPI-2-RF
      intercorrelations produced from the two forms yielded mostly small and a few
      medium differences, indicating that discriminant validity and test structure are
      maintained. Overall, our findings reflect the internal structure comparability of
      MMPI-2-RF scale scores generated from MMPI-2 and MMPI-2-RF booklets. Implications
      of these results and limitations of these findings are discussed. 

PMID- 24934217
TI  - Gain and loss of function of P2X7 receptors: mechanisms, pharmacology and
      relevance to diabetic neuropathic pain.
AB  - BACKGROUND: Genetic causes of exaggerated or reduced pain sensitivity in humans
      are well known. Recently, single nucleotide polymorphisms (SNPs) in the gene
      P2RX7, coding for the ATP-gated ion channel P2X7, have been described that cause
      gain-of-function (GOF) and loss-of-function (LOF), respectively of this channel.
      Importantly, P2RX7 SNPs have been associated with more or less severe pain scores
      in patient suffering of post-mastectomy pain and osteoarthritis. RESULTS: The
      functional consequences of some P2RX7 SNPs (rs208294 (His155Tyr), rs1718119
      (Ala348Thr) and rs3751143 (Glu496Ala)) were studied in recombinant cells in
      vitro. Our findings suggest a correlation between GOF and LOF of P2X7 and actual
      channel protein expression. Both channel and pore function for these mutant P2X7
      receptors changed in parallel to protein levels. On the other hand, the mutant
      receptors did not differ in their sensitivity to known P2X7 agonists and
      antagonists. We further demonstrated that in patients with diabetic peripheral
      neuropathic pain (DPNP), the presence of the GOF SNPs rs208294 (His155Tyr) and
      rs1718119 (Ala348Thr) is associated, in females, with higher pain intensity
      scores. CONCLUSIONS: Our present results confirm the physiological relevance of
      some of the SNPs in the P2RX7 gene and show that the presence of these genetic
      variants correlates with pain sensitivity also in a diabetic neuropathic pain
      patient population.

PMID- 24934219
TI  - On improving the use of OCT imaging for detecting glaucomatous damage.
AB  - AIMS: To describe two approaches for improving the detection of glaucomatous
      damage seen with optical coherence tomography (OCT). METHODS: The two approaches
      described were: one, a visual analysis of the high-quality OCT circle scans and
      two, a comparison of local visual field sensitivity loss to local OCT retinal
      ganglion cell plus inner plexiform (RGC+) and retinal nerve fibre layer (RNFL)
      thinning. OCT images were obtained from glaucoma patients and suspects using a
      spectral domain OCT machine and commercially available scanning protocols. A high
      quality peripapillary circle scan (average of 50), a three-dimensional (3D) scan
      of the optic disc, and a 3D scan of the macula were obtained. RGC+ and RNFL
      thickness and probability plots were generated from the 3D scans. RESULTS: A
      close visual analysis of a high-quality circle scan can help avoid both false
      positive and false negative errors. Similarly, to avoid these errors, the
      location of abnormal visual field points should be compared to regions of
      abnormal RGC+ and RNFL thickness. CONCLUSIONS: To improve the sensitivity and
      specificity of OCT imaging, high-quality images should be visually scrutinised
      and topographical information from visual fields and OCT scans combined.

PMID- 24934220
TI  - Optical coherence tomography imaging of macular oedema.
AB  - Macular oedema (ME) occurs in a wide variety of pathological conditions and
      accounts for different degrees of vision loss. Early detection of ME is therefore
      critical for diagnosis and therapeutic management. Optical coherence tomography
      (OCT) is a non-contact, diagnostic method that uses infrared light, which allows
      the analysis of the retinal structure by means of high-resolution tomographic
      cross sections. The identification, localisation, quantification and long-term
      follow-up of fluid collections are the most important capabilities of OCT. Since
      the introduction of OCT in clinical practice, it has become an invaluable
      diagnostic tool and different patterns of ME have been reported. The purpose of
      this manuscript is to review OCT profiles of ME according to the aetiology and
      describe what has been reported regarding intraretinal features in vivo. 

PMID- 24934221
TI  - Recent advances in OCT imaging of the lamina cribrosa.
AB  - The lamina cribrosa (LC) is believed to be the site of injury to retinal ganglion
      cell axons in glaucoma. The ability to visualise this structure has the potential
      to help increase our understanding of the disease and be useful in the early
      detection of glaucoma. While for many years the research on the LC was
      essentially dependent on histology and modelling, a number of recent advances in
      optical coherence tomography (OCT) have dramatically improved the ability to
      visualise the LC, such that it is now possible to image the LC in vivo in humans
      and animals. In this review, we highlight recent advances in OCT imaging of the
      LC, in the technology, processing and analysis, and discuss the impact that these
      will have on the ability to diagnose and monitor glaucoma, as well as to expand
      our understanding of its pathophysiology. With this manuscript, we aspire to
      share our excitement on the achievements and potential of recent developments as
      well as advise caution regarding the challenges that remain before imaging of the
      LC and optic nerve can be used routinely in clinical practice. 

PMID- 24934222
TI  - Assessing copper status in pediatric patients receiving parenteral nutrition.
AB  - BACKGROUND: Copper is a trace mineral essential for numerous physiological
      processes. The purpose of this article is to provide data on copper levels in
      pediatric patients receiving parenteral nutrition (PN) that are useful to guide
      supplementation in PN formulation. METHOD: This is a retrospective review of
      hospitalized pediatric patients receiving PN supplemented and not supplemented
      with copper. In total, 751 supplemented pediatric patients and 90 pediatric
      patients not supplemented had serum copper levels measured. We assessed patient
      demographics, days on PN before copper level was drawn, serum copper levels,
      conjugated bilirubin levels, and C-reactive protein (CRP). RESULTS: The mean
      serum copper level was 80 mcg/dL at 20 days for supplemented patients and 64
      mcg/dL at 14 days for the 90 nonsupplemented patients (P = .0002). In the
      supplemented patients, 50% of the levels were low and 45% were within the normal
      range. The remaining 5% of patients had high levels. In nonsupplemented patients,
      71% were low and 29% within the normal range. There was no correlation between
      copper levels and conjugated bilirubin <2 mg/dL and >2 mg/dL (P = .3421). Copper
      levels correlated with CRP for CRP >4 mg/dL (P = .03). CONCLUSION: Pediatric
      patients receiving PN should be supplemented with copper to prevent deficiency.
      Serum copper levels should be assessed at 14 days. Assessment of copper status
      should not be determined by conjugated bilirubin levels. Serum copper levels may
      be elevated in patients with acute inflammation and may be falsely elevated when
      CRP is >4 mg/dL.

PMID- 24934223
TI  - Phosphorylation of pyruvate kinase A by protein kinase J leads to the altered
      growth and differential rate of intracellular survival of mycobacteria.
AB  - PknJ (Rv2088) is a serine/threonine protein kinase of mycobacteria which is
      present in Mycobacterium tuberculosis (MTB), but its gene is absent in
      Mycobacterium smegmatis (MS); a fast grower and nonpathogenic species of
      mycobacteria. The heterologous expression of MTB-specific PknJ in MS altered the
      growth of recombinant mycobacteria highlighting one of the characteristics of
      this protein. This nature of the protein was further confirmed when Mycobacterium
      bovis BCG (BCG) containing antisense copy of pknJ resulted in the increased
      growth of BCG. The real-time RNA quantification analysis pointed out toward
      increased expression of this protein during infection of THP-1 macrophage cells
      which further emphasized that the protein is essential for the intracellular
      survival of mycobacteria. The differential in gel electrophoresis (DIGE) data
      followed by mass spectroscopy suggested that PknJ is involved in regulation of
      pyruvate kinase A (Rv1617). Since pyruvate kinase (PK) A is one of the key
      enzymes which controls glycolytic cycle in mycobacteria, we looked for its
      interaction with PknJ during extracellular and intracellular growth of
      mycobacteria. In order to identify the specific residue(s) involved in post
      translational modification, the phospho-null mutants of PK were generated, and
      their substrate specificities in response to PknJ were assessed through kinase
      assay. The findings thus underlined that the PK activity is predominantly
      dependent on the threonine residue at the 94(th) position and further suggested
      that this site may be plausible in intracellular survival of mycobacteria upon
      phosphorylation with PknJ.

PMID- 24934225
TI  - Preparation and in-vitro transfection efficiency evaluation of modified cationic
      liposome-polyethyleneimine-plasmid nanocomplexes as a novel gene carrier.
AB  - Liposome-linear polyethyleneimine (PEI)-DNA nanocomplexes have shown to be
      effective non-viral gene delivery vectors. In the present study, we tried to
      improve the transfection efficiency of these nanocomplexes by liposome
      modification. For this purpose, the lipopolymer was prepared by the conjugation
      of hexylacrylate to the PEI. Liposomes comprising lipopolymer and DOTAP (1.2
      DiOleoyl-3-Trimethyl Ammonium-Propane) were prepared and extruded through
      polycarbonate filters to obtain the desired size. The 2.5, 25 and 250 KDa
      molecular weights of linear PEI have been used in order to prepare modified
      liposome-PEI-DNA nanocomplexes. Three C/P ratios of each nancomplex were
      premixed. Size, zeta potential and the DNA condensation ability of these
      complexes were determined separately, and in the end, the transfection efficiency
      and cell cytotoxicity of prepared vectors were evaluated on Neuro2A cell line.
      Mean particle size of all of these nanocomplexes was lower than 220 nm with
      surface charge of 17.5 to 25.9 mV. The lipopolyplexes (comprising modified
      liposome:PEI:DNA), modified liposome (as lipoplex) and PEI 250KDa (as polyplex)
      showed the highest transfection efficacy. This activity was amplified by increase
      carrier to plasmid (C/P) ratio. In addition, the metabolic activity of prepared
      vectors was 80-100% for control group. In conclusion, the prepared lipopolyplexes
      showed high ability to enhance gene transfer. 

PMID- 24934224
TI  - Multicilin drives centriole biogenesis via E2f proteins.
AB  - Multiciliate cells employ hundreds of motile cilia to produce fluid flow, which
      they nucleate and extend by first assembling hundreds of centrioles. In most
      cells, entry into the cell cycle allows centrioles to undergo a single round of
      duplication, but in differentiating multiciliate cells, massive centriole
      assembly occurs in G0 by a process initiated by a small coiled-coil protein,
      Multicilin. Here we show that Multicilin acts by forming a ternary complex with
      E2f4 or E2f5 and Dp1 that binds and activates most of the genes required for
      centriole biogenesis, while other cell cycle genes remain off. This complex also
      promotes the deuterosome pathway of centriole biogenesis by activating the
      expression of deup1 but not its paralog, cep63. Finally, we show that this
      complex is disabled by mutations in human Multicilin that cause a severe
      congenital mucociliary clearance disorder due to reduced generation of multiple
      cilia. By coopting the E2f regulation of cell cycle genes, Multicilin drives
      massive centriole assembly in epithelial progenitors in a manner required for
      multiciliate cell differentiation. 

PMID- 24934226
TI  - Temporal separation in the release of bioactive molecules from a moldable calcium
      sulfate bone graft substitute.
AB  - Treatment of infected bone defects presents a considerable challenge due to the
      complications that occur from significant bone damage concomitant with
      contaminated tissue. These wounds are most often treated in a two-step sequence,
      where the infection is first eliminated before any attempt to repair the bone is
      undertaken. In order to combine these two treatment steps into one procedure, a
      moldable bone grafting material was developed to deliver drugs in a temporally
      separated manner. This was accomplished by a two-layered calcium sulfate
      composite consisting of a moldable outer shell containing antibiotic-loaded
      poly(lactic-co-glycolic acid) microspheres wrapped around a preformed core
      containing an osteogenic drug. The release of vancomycin from the shell portion
      began immediately and continued over the course of 6 weeks, while the release of
      simvastatin from the core was delayed for 12 days before being released over the
      next 4 weeks. Bioactivity of vancomycin was shown in modified Kirby-Bauer
      experiments in which whole samples inhibited Staphylococcus aureus (S. aureus)
      growth for 2 weeks. This two-layered system is capable of delivering antibiotics
      locally for clinically relevant periods of time and delaying the release of
      osteogenic drugs to mimic a two-step procedure that has potential for treating
      infected bone defects. 

PMID- 24934227
TI  - Smoking is associated with impaired glucose regulation and a decrease in insulin
      sensitivity and the disposition index in first-degree relatives of type 2
      diabetes subjects independently of the presence of metabolic syndrome.
AB  - The aim of this study was to investigate glucose tolerance, insulin secretion and
      insulin resistance according to smoking habits in first-degree relatives of type
      2 diabetes patients, a population at high risk for developing diabetes. One
      thousand three hundred (646 females and 654 males) subjects underwent an oral
      glucose tolerance test (OGTT) to investigate their glucose metabolism and
      answered questionnaires about their lifestyle habits. Smoker subjects showed
      significant impairment compared with non-smoker subjects in 2-h post-oral glucose
      tolerance test (2hOGTT, 129.3 +/- 40.2 vs. 117.7 +/- 37.6 mg/dl, p < 0.001), the
      OGTT insulin sensitivity (386.3 +/- 54.9 vs. 400.5 +/- 53.4 ml min(-1) m(2), p <
      0.01) method and the insulin sensitivity and secretion index-2 (ISSI-2, 1.7 +/-
      0.8 vs. 2.0 +/- 1.0, p < 0.005). Metabolic syndrome (MS) was higher in the smoker
      than in the non-smoker group (46.5 vs. 29.7 %, p < 0001), and smokers were more
      sedentary than non-smokers (3.94 +/- 3.77 vs. 4.86 +/- 4.41 h/week, p < 0.001).
      Smokers showed an increased risk of impaired glucose regulation (IGR: impaired
      glucose tolerance or diabetes mellitus) with a hazard ratio (HR) adjusted by
      gender, metabolic syndrome and physical activity of 1.78, 95 % CI 1.27-2.47 (p <
      0.001). The association between smoking and MS conferred a risk of IGR that was
      five times higher (HR 5.495, 95 % CI 4.07-7.41, p < 0.001). Smoking habit was a
      significant explanatory variable in a multiple forward stepwise regression
      analysis performed using 2hOGTT and ISSI-2 as dependent variables (p < 0.0001, R
      = 0.313 and p < 0.0001, R = 0.347, respectively). In conclusions, our results
      show that tobacco smoking is tightly associated with impairments in glucose
      metabolism and insulin sensitivity and insulin secretion. 

PMID- 24934228
TI  - Psychophysiological responses of artificial gravity exposure to humans.
AB  - AIM: The aim of this study was to determine psychophysiological responses and
      cognitive performance after a single bout of artificial gravity, in order to
      investigate its use as a potential holistic countermeasure for long-duration
      human space flight, considering mental health. METHODS: Sixteen male participants
      were exposed to two different hypergravity protocols in a randomized order, one
      providing a constant +2 Gz environment for 30 min, the other providing
      participants for five times with repeated 3-min intervals of +2 Gz and rest,
      respectively. EEG was recorded prior, during and after AG. In addition, self
      reported mood and cognitive performance was assessed before and after AG
      exposure. EEG data were analyzed using standardized brain electromagnetic
      tomography (sLORETA). RESULTS: Beta-1 EEG activity (12-18 Hz) was decreased in
      the left middle frontal gyrus after the continuous profile. Participants'
      motivation decreased after continuous artificial gravity, while perceived
      physical state was increased. The intermittent profile did not induce any changes
      in the observed parameters. Cognitive performance was not affected by either of
      both profiles. CONCLUSION: The continuous profile induced neurophysiological
      changes, which are considered with negative affect and withdrawal related
      motivation, according to the model of frontal asymmetry. This notion was further
      confirmed by decreases in self-reported mood after continuous AG. Therefore, the
      continuous profile would not be appropriate for the human space flight program.
      Intermittent AG did not induce any psychophysiological changes and might
      therefore provide a more appropriate approach as a countermeasure for further
      investigations.

PMID- 24934229
TI  - The effect of muscle vibration on short latency intracortical inhibition in
      humans.
AB  - PURPOSE: The purpose of the present study was to investigate the effect of muscle
      vibration (MV) on short latency intracortical inhibition (SICI) and facilitation
      (ICF) assessed by paired-pulse transcranial magnetic stimulation (TMS). METHODS:
      Nineteen right-handed healthy subjects were investigat ed without and with MV of
      the right extensor carpi radialis (ECR), using single- and paired-pulse TMS with
      interstimulus interval (ISI) of 3 and 13 ms. Intensities of the conditioning and
      test stimulus were 70 and 120 % of the motor threshold at rest. The motor-evoked
      potentials (MEPs) were recorded simultaneously from the vibrated ECR and its
      antagonist flexor carpi radialis (FCR). RESULTS: In all the subjects a SICI of
      similar strength could be observed at 3 ms, at rest and during MV both in the
      vibrated muscle as well as in its antagonist. The subjects were divided in two
      groups according to the changes in MEP response to paired-pulse TMS with 13 ms
      ISI observed during MV. In nine subjects SICI was evident also at 13 ms when
      vibration was applied, while in another ten subjects vibration induced ICF at 13
      ms. CONCLUSIONS: The effect of MV is not just a facilitation of SICI, but a
      stronger prolongation of the effect of intracortical inhibition to an ISI at
      which ICF is well pronounced, when the intensity of the conditioning stimulus
      exceeds the threshold for intracortical facilitation.

PMID- 24934230
TI  - [Chronic motility disorders of the upper gastrointestinal tract in the elderly.
      Pharmaceutical, endoscopic and operative therapy].
AB  - Primary motility disorders of the upper gastrointestinal (GI) tract result from
      an impairment of the motor function of the esophagus, stomach, and duodenum by
      malfunction of the enteric nervous system or degeneration of the gastrointestinal
      muscle layer. Other forms of upper GI motility disorders occur secondary to
      underlying systemic diseases. The exact pathophysiology of the disturbances
      within the enteric nervous system of the upper GI tract is not yet clearly
      understood. For motility disorders resulting from systemic diseases the lack of
      knowledge with respect to the underlying pathomechanism is even greater. The term
      functional dyspepsia summarizes some symptoms of the upper abdomen, suggesting a
      disorder of upper GI motility or perception; however, this link to disturbed
      physiology has never been convincingly demonstrated. This overview describes
      therapeutic options for motility disorders of the upper GI tract regarding
      medicinal, endoscopic and surgical targets. The efficacy of medicinal therapy of
      upper GI motility disorders is low due to the lack of understanding of the
      pathophysiology. Therefore, endoscopic and other interventional therapies have to
      be applied also in the elderly patient group. The restrictions for metoclopramide
      published by the European Medicines Agency (EMA) in July 2013 have limited the
      armentarium of medicinal therapy of chronic motility disorders of the upper GI
      tract. 

PMID- 24934231
TI  - In vitro model of hyaluronan synthase gene expression associated with
      lipopolysaccharide-induced inflammation in SW982 cell line.
AB  - The present study aimed to demonstrate the phenomena of hyaluronan synthesis in
      response to lipopolysaccharide-induced inflammation in SW982, a human synovial
      sarcoma cell line. The expression of IL-1beta, including Toll-like receptor 4 and
      IL-1beta-converting enzyme, was proved to be induced by a reverse transcription
      polymerase chain reaction. The expression of HAS genes encoding enzyme hyaluronan
      synthase 2 and 3, including CD44 gene which encodes the cell surface receptor of
      hyaluronan were upregulated in association with the activation of inflammation,
      along with an increase in hyaluronan level in the culture medium. The highest
      expression of HAS2 and HAS3 was found at 9 h after treatment with
      lipopolysaccharide. However, HAS1 gene expression was not detectable neither with
      the non-treatment nor with the treatment with lipopolysaccharide. Dexamethasone
      at 30 nM significantly suppressed lipopolysaccharide-induced HAS genes
      expression, leading to the decline of the hyaluronan level in the culture medium.
      Our results demonstrated the effective tool for studying hyaluronan synthesis in
      association with inflammation in the SW982 cell line.

PMID- 24934232
TI  - Optimization of culture condition of human bone marrow stromal cells in terms of
      purification, proliferation, and pluripotency.
AB  - Human bone marrow stromal cells (hBMSCs) possess multilineage differentiation
      potential and play an important role in modern tissue engineering. However, the
      development of culture media to maintain hBMSCs in an undifferentiated, self
      renewing state during their robust proliferation remains a challenge. We
      developed and tested modified growth medium [medium 1: epidermal growth factor
      (EGF), platelet-derived growth factor (PDGF), low glucose, 2% fetal calf serum
      (FCS)] on hBMSCs by comparing primary cell isolation, multipassage expansion,
      culture morphology, proliferation, and cellular phenotype, and performing an
      expression analysis of intrinsic-regulated genes to other two media. Cell
      morphology, proliferation, and phenotype varied among the media, while cells
      cultured in medium 1 displayed small, spindle-shaped morphology with the highest
      rate of growth capacities and the expected phenotype. RT-PCR analysis showed that
      medium 1 displayed the lowest expression levels of osteogenic genes, chondrogenic
      genes (osteonectin, runt-related transcription factor 2, cartilage oligo matrix
      protein, and SOX9), and adipogenic genes (lipoprotein lipase). The expression of
      another adipogenic gene, peroxisome proliferator-activator receptor-gamma2, was
      higher in medium 1 but did not reach significance. In addition, hBMSCs expanded
      in medium 1 showed the highest expression ratio of self-renewing-related genes
      Kruppel-like factor 2 (KLF2) and KLF5. In conclusion, medium 1 allows for better
      expansion and pluripotency maintenance of hBMSCs and serves as a preferred
      alternative to traditional serum-containing media for research applications and
      future clinical use. 

PMID- 24934233
TI  - Long-term adaptation of the Bombyx mori BmN4 cell line to grow in serum-free
      culture.
AB  - Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a
      commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum
      containing TC-100 medium content from 100 to 0% (v/v). The BmN4 cells adapted to
      the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell
      morphology. The BmN-SFM was subcultured 200 times, and the population doubling
      time was 4.70 d. Infection studies showed that BmN-SFM cells were easily
      susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication
      of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells
      were almost the same as those in BmN4 cells before adaptation. Additionally,
      mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and
      modified with N-linked glycans in BmN-SFM cells. These findings indicate that BmN
      SFM is particularly useful for a BmNPV-based baculovirus expression vector system
      with serum-free conditions.

PMID- 24934234
TI  - Cell kinetics, DNA integrity, differentiation, and lipid fingerprinting analysis
      of rabbit adipose-derived stem cells.
AB  - Human adipose tissue has been described as a potential alternative reservoir for
      stem cells. Although studies have been performed in rabbits using autologous
      adipose-derived stem cells (ADSC), these cells have not been well characterized.
      The primary objectives of this study were to demonstrate the presence of adipose
      derived stem cells isolated from rabbit inguinal fat pads and to characterize
      them through osteogenic and adipogenic in vitro differentiation and lipid
      fingerprinting analysis. The secondary objective was to evaluate cell behavior
      through growth kinetics, cell viability, and DNA integrity. Rabbit ADSCs were
      isolated to determine the in vitro growth kinetics and cell viability. DNA
      integrity was assessed by an alkaline Comet assay in passages 0 and 5. The
      osteogenic differentiation was evaluated by Von Kossa, and Alizarin Red S
      staining and adipogenic differentiation were assessed by Oil Red O staining.
      Lipid fingerprinting analyses of control, adipogenic, and osteogenic
      differentiated cells were performed by MALDI-TOF/MS. We demonstrate that rabbit
      ADSC have a constant growth rate at the early passages, with increased DNA
      fragmentation at or after passage 5. Rabbit ADSC viability was similar in
      passages 2 and 5 (90.7% and 86.6%, respectively), but there was a tendency to
      decreased cellular growth rate after passage 3. The ADSC were characterized by
      the expression of surface markers such as CD29 (67.4%) and CD44 (89.4%), using CD
      45 (0.77%) as a negative control. ADSC from rabbits were successfully isolated
      form the inguinal region. These cells were capable to differentiate into
      osteogenic and adipogenic tissue when they were placed in inductive media. After
      each passage, there was a trend towards decreased cell growth. On the other hand,
      DNA fragmentation increased at each passage. ADSC had a different lipid profile
      when placed in control, adipogenic, or osteogenic media. 

PMID- 24934235
TI  - Maintenance of primary cell cultures of immunocytes from Cacopsylla spp.
      psyllids: a new in vitro tool for the study of crop pest insects.
AB  - Primary cell cultures of immunocytes have been developed from the three psyllid
      species Cacopsylla melanoneura, Cacopsylla pyri (vectors of 'Candidatus
      Phytoplasma mali' and 'Candidatus Phytoplasma pyri', respectively) and Cacopsylla
      crataegi. The medium most suitable of those evaluated was Hert-Hunter 70 (HH70)
      psyllid medium. In fact, good survival and proliferation of the Cacopsylla
      immunocytes for over 60 d were observed, with mitosis activities starting at 15-d
      post culture. Moreover, adhesion and phagocytosis activities were confirmed for
      all the psyllid cell cultures by functionality tests. Morphological examination
      of cultured immunocytes revealed the presence of different cell types in all the
      three psyllid species in accordance to published data about insect immunocytes.
      The in vitro maintenance of psyllid immunocytes represents a powerful tool for a
      wide range of applications, especially for psyllid cell biology. In particular,
      in-depth studies on the biology of psyllids as vector insects as well as analyses
      to understand the mechanisms behind the interactions with pathogens and symbionts
      are now possible. These cultures can be used as an in vitro model to study
      psyllid humoral immune responses, which also will allow in-depth investigations
      on the abilities of psyllids as vectors of phytoplasmas. All these applications
      provide new opportunities to develop more focused and specific pest control
      strategies.

PMID- 24934236
TI  - Reduced levels of circulating endothelial progenitor cells in acute myocardial
      infarction patients with diabetes or pre-diabetes: accompanying the glycemic
      continuum.
AB  - BACKGROUND: Diabetic patients have a significantly worse prognosis after an acute
      myocardial infarction (AMI) than their counterparts. Previous studies have shown
      that the number of circulating endothelial progenitor cells (EPCs) significantly
      increase early after an AMI in normoglycemic patients. However, it is well known
      that type 2 diabetes mellitus (DM) is associated with impaired function and
      reduced circulating EPCs levels. Nonetheless, few studies have analyzed EPCs
      response of diabetics to an AMI and the EPC response of pre-diabetic patients has
      not been reported yet. Therefore, we hypothesized that in the acute phase of an
      AMI, diabetic and pre-diabetics have lower circulating EPCs levels than patients
      with normal glucose metabolism. We also evaluated the possible capacity of
      chronic antidiabetic treatment in the recovery of EPCs response to an AMI in
      diabetics. METHODS: One-hundred AMI patients were prospectively enrolled in the
      study. Using the high-performance flow cytometer FACSCanto II, circulating EPCs
      (CD45dimCD34+KDR+ and CD45dimCD133+KDR+ cells) were quantified, within the first
      24 hours of admission. In addition, as an indirect functional parameter, we also
      analyzed the fraction of EPCs coexpressing the homing marker CXCR4. RESULTS: We
      found that in the acute phase of an AMI, diabetic patients presented
      significantly lower levels of circulating CD45dimCD34+KDR+ and CD45dimCD133+KDR+
      EPCs by comparison with nondiabetics, with a parallel decrease in the
      subpopulations CXCR4+ (p < 0.001). Indeed, this study suggests that the impaired
      response of EPCs to an AMI is an early event in the natural history of DM, being
      present even in pre-diabetes. Our results, also demonstrated that numbers of all
      EPCs populations were inversely correlated with HbA1c (r = -0.432, p < 0.001 for
      CD45dimCD34+KDR+ cells). Finally, this study suggests that previous chronic
      insulin therapy (but not oral antidiabetic drugs) attenuate the deficient
      response of diabetic EPCs to an AMI. CONCLUSION: This study indicates that there
      is a progressive decrease in EPCs levels, from pre-diabetes to DM, in AMI
      patients. Moreover, glycemic control seems to be determinant for circulating EPCs
      levels presented in the acute phase of an AMI and chronic insulin therapy may
      probably attenuate the deficit in EPCs pool seen in diabetics.

PMID- 24934237
TI  - Association of experience with illness and end-of-life care with advance care
      planning in older adults.
AB  - OBJECTIVES: To examine whether experiences with illness and end-of-life care are
      associated with readiness to participate in advance care planning (ACP). DESIGN:
      Observational cohort study. SETTING: Community. PARTICIPANTS: Persons aged 60 and
      older recruited from physician offices and a senior center. MEASUREMENTS:
      Participants were asked about personal experience with major illness or surgery
      and experience with others' end-of-life care, including whether they had made a
      medical decision for someone dying, knew someone who had a bad death due to too
      much or too little medical care, or experienced the death of a loved one who made
      end-of-life wishes known. Stages of change were assessed for specific ACP
      behaviors: completion of living will and healthcare proxy, communication with
      loved ones regarding life-sustaining treatments and quantity versus quality of
      life, and communication with physicians about these same topics. Stages of change
      included precontemplation, contemplation, preparation, and action or maintenance,
      corresponding to whether the participant was not ready to complete the behavior,
      was considering participation in the next 6 months, was planning participation
      within 30 days, or had already participated. RESULTS: Of 304 participants, 84%
      had one or more personal experiences or experience with others. Personal
      experiences were not associated with greater readiness for most ACP behaviors. In
      contrast, having one or more experiences with others was associated with greater
      readiness to complete a living will and healthcare proxy, discuss life-sustaining
      treatment with loved ones, and discuss quantity versus quality of life with loved
      ones and with physicians. CONCLUSION: Older individuals who have experience with
      end-of-life care of others demonstrate greater readiness to participate in ACP.
      Discussions with older adults regarding these experiences may be a useful tool in
      promoting ACP.

PMID- 24934238
TI  - Scanning for PIT-tagged flatfish in a coastal area using a sledge equipped with
      an RFID antenna.
AB  - A radio frequency identification (RFID) antenna system, build into a sledge that
      can be towed behind a vessel like a trawl and thereby has the potential to detect
      the position of a passive inductor technology (PIT)-tagged fish in a wide variety
      of habitats, is presented. By scanning for hatchery-reared PIT-tagged turbot
      Psetta maxima released into a natural habitat, the performance of the system was
      compared to a standard juvenile trawl and results suggested that the efficiency
      of the sledge was five times that of the trawl, which in absolute values
      corresponds to 75% of P. maxima lying in the pathway of the sledge. 

PMID- 24934239
TI  - The direct effect of estrogen on cell viability and apoptosis in human gastric
      cancer cells.
AB  - Epidemiology researches indicated that gastric cancer is a male-predominant
      disease; both expression level of estrogen and expression pattern of estrogen
      receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen
      on gastric cancer cells is still unclear. This study aimed to explore the direct
      effect of beta-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were
      treated with a serial of concentrations of E2. The survival rates of both the
      cell lines were significantly reduced, and the reduction of viability was due to
      apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the
      increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3
      fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were
      reduced. Apoptosis was further confirmed by flow cytometry. The expression level
      of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both
      ERalpha and ERbeta were expressed in these cell lines, and the result of
      bioinformatics analysis of gastric cancer from GEO datasets indicated that the
      expression levels of both ERalpha and ERbeta were significantly higher in
      noncancerous gastric tissues than in gastric cancer tissues. Our research
      indicated that estrogen can reduce cell viability and promote apoptosis in
      gastric cancer cells directly; ERs expression level is associated with gastric
      cancer. Our research will help to understand the mechanism of gender disparity in
      gastric cancer. 

PMID- 24934240
TI  - Endocan, a potential prognostic and diagnostic biomarker of acute leukemia.
AB  - Recent evidence indicated that endocan may be a potential cell marker and a new
      target for cancers including acute leukemia since the serum endocan level in
      patients with acute leukemia was associated with the status of the disease, i.e.,
      endocan was higly expressed in untreated acute leukemia, but decreased after
      chemotherapy and increased again during bone marrow regeneration. The present
      study showed that there was high level expression of endocan in cytoplasm of bone
      marrow blasts of patients with acute myeloid leukemia or acute lymphoblastic
      leukemia. The expression level of endocan was significantly decreased when the
      patients underwent remission after chemotherapy and re-bounces back when the
      acute leukemia relapsed. No obvious change in expression of endocan was observed
      before and after chemotherapy if the patients showed no remission after
      chemotherapy. (N-(4-Hydroxyphenyl)  retinamide), a potent anti-angiogenic agent,
      could not only down-regulate the expression of vascular epithelial growth factor,
      but also decrease endocan transcription and expression in NB4 cells, a human
      acute promyelocytic leukemia cell line. These observations suggest that endocan
      could act as a predictor for the severity and the prognosis of acute leukemia.
      The findings could be used as the basis for future targeted therapy directed
      against bone marrow angiogenesis in acute leukemia treatment. 

PMID- 24934241
TI  - Der p 2 promotes motility of airway epithelial cell attributing to AKT/GSK3beta
      associated epithelial-to-mesenchymal transition.
AB  - Enhanced motility of epithelial cell plays a critical role in airway repair and
      remodeling involved in respiratory disorders such as asthma. Der p 2 (DP2) is a
      major allergen derived from Dermatophagoides pteronyssinus, the major source of
      indoor allergens causing airway hypersensitiveness. Herein, we hypothesized that
      DP2 may promote airway epithelial cell motility involved in airway remodeling.
      Using human bronchial cell BEAS-2B as cell model incorporating with
      immunoblotting and real-time quantitative PCR, our results revealed that DP2
      significantly diminished epithelial marker E-cadherin and elevated mesenchymal
      marker vimentin and alpha-smooth muscle actin (alpha-SMA) in both protein and
      mRNA levels. Additionally, DP2 altered BEAS-2B cell morphology from cobblestone
      like to fibroblast-like shape with reduced cell-cell contact. In parallel,
      nuclear translocation of Snail and Slug, the transcriptional repressors of E
      cadherin, was increased in response to DP2. Further investigation showed that
      activation of AKT and extracellular response-regulated kinase 1/2 and inhibition
      of glycogen synthase kinase-3beta (GSK3beta) was involved in translocation of
      Snail/Slug triggered by DP2. In addition to regulation of epithelial and
      mesenchymal markers, DP2 enhanced cell motility of the airway epithelial cell
      associating with AKT/GSK3beta signaling using wound healing assay and invasion
      assay. In conclusion, DP2 not only altered expression of E-cadherin, vimentin,
      and alpha-SMA, but also enhanced migration and invasiveness of epithelial cell,
      attributing to modulation of AKT/GSK3beta signaling and Snail/Slug translocation.
      These findings also suggested that DP2 may initiate epithelial-mesenchymal
      transition involved in airway remodeling. 

PMID- 24934242
TI  - Metabolic derangement and cardiac injury early after reperfusion following
      intermittent cross-clamp fibrillation in patients undergoing coronary artery
      bypass graft surgery using conventional or miniaturized cardiopulmonary bypass.
AB  - Myocardial ischemic stress and early reperfusion injury in patients undergoing
      coronary artery bypass grafting (CABG) operated on using intermittent cross-clamp
      fibrillation (ICCF) are not presently known. The role of mini-cardiopulmonary
      bypass (mCPB) versus conventional CPB (cCPB) during ICCF has not been
      investigated. These issues have been addressed as secondary objective of
      randomised controlled trial (ISRCTN30610605) comparing cCPB and mCPB. Twenty-six
      patients undergoing primary elective CABG using ICCF were randomised to either
      cCPB or mCPB. Paired left ventricular biopsies collected from 21 patients at the
      beginning and at the end of CPB were used to measure intracellular substrates
      (ATP and related compounds). Cardiac troponin T (cTnT) and CK-MB levels were
      measured in plasma collected from all patients preoperatively and after 1, 30,
      60, 120, and 300 min after institution of CPB. ICCF was associated with
      significant ischemic stress as seen by fall in energy-rich phosphates early after
      reperfusion. There was also a fall in nicotinamide adenine dinucleotide (NAD(+))
      indicating cardiomyocyte death which was confirmed by early release of cTnT and
      CK-MB during CPB. Ischemic stress and early myocardial injury were similar for
      cCPB and mCPB. However, the overall cardiac injury was significantly lower in the
      mCPB group as measured by cTnT (mean +/- SEM: 96 +/- 14 vs. 59 +/- 8 ug/l, p =
      0.02), but not with CK-MB. ICCF is associated with significant metabolic
      derangement and early myocardial injury. This early outcome was not affected by
      the CPB technique. However, the overall cardiac injury was lower for mCPB only
      when measured using cTnT. 

PMID- 24934243
TI  - Antidepressant and antipsychotic drugs differentially affect PON1 enzyme
      activity.
AB  - Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)
      associated, calcium-dependent enzyme. In this study, the effects of Haloperidol,
      Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of
      antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was
      studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme
      was purified from human blood using two-step procedures, namely, ammonium sulfate
      precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction
      chromatography. The overall purification of human serum PON1 was obtained in a
      activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDS
      polyacrylamide gel electrophoresis of the enzyme indicates a single band with an
      apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and
      fluoxetine hydrocloride were effective inhibitors on purified human serum PON1
      activity with IC50 of 0.187 and 3.08 mM values, respectively. The kinetics of
      interaction of haloperidol and fluoxetine hydrocloride with the purified human
      serum PON1 indicated uncompetitive inhibiton pattern with Ki of 4.15 and 0.007
      mM, respectively.

PMID- 24934244
TI  - Profiling the chemical content of Ficus lyrata extracts via UPLC-PDA-qTOF-MS and
      chemometrics.
AB  - This study attempts to elucidate the secondary metabolite profiles of Ficus
      lyrata leaves and fruits grown in Egypt. Non-targeted metabolite profiling via
      ultra performance liquid chromatography (UPLC)-qTOF-MS was used to identify
      various chemical classes in F. lyrata fruits and leaves (i.e. flavonoids,
      phenolic acids and fatty acids) analysed by chemometrics. A total of 72
      metabolites were evaluated via a UPLC-qTOF-MS-based metabolomic study. Seventeen
      flavonoids were characterised and tentatively identified with the main
      constituents being catechins/procyanidins, O- and C-linked flavonoid glycosides.
      The major procyanidins were dimers and trimers comprising (epi)catechin and
      (epi)afzelechin units, whereas the predominant flavones were C-glycosides of
      luteolin and apigenin. Aside from these major flavonoid classes, a group of
      benzoic acids, caffeoylquinic acids, fatty acid and sphingolipids were also
      annotated. This study provides the most complete map for polyphenol distribution
      in F. lyrata leaves and fruits and the basis for future investigation of its
      fruits nutritional value or possible nutraceutical uses. 

PMID- 24934245
TI  - Cribriform-morular variant of papillary thyroid carcinoma: an indication to
      screen for occult FAP.
AB  - Cribriform-morular variant (CMV) is a rare subtype of papillary thyroid carcinoma
      (PTC) that is associated with familial adenomatous polyposis (FAP). Given the
      high likelihood for multi-organ malignancies in FAP patients, this study explores
      the yield of diagnosing occult FAP among CMV-PTC patients. Institutional database
      was searched in order to identify patients with pathologically-confirmed CMV-PTC
      from 2000 to 2012. Medical records were reviewed, and clinical and pathological
      features were analyzed. Eleven cases of CMV were identified from 6,901 patients
      with PTC, for a prevalence of 0.16 %. All 11 patients were female. The median age
      at CMV-PTC diagnosis was 36 years (range 18-46). Two patients had pre-existing
      FAP at the time of PTC diagnosis. The other nine patients were referred for
      colonoscopy and/or genetic testing. Six patients underwent colonoscopy and one
      (17 %) was diagnosed with FAP based on polyposis phenotype and genetic testing.
      The mean age of patients at the time of CMV-PTC diagnosis was younger in the FAP
      group (23 years, range 18-34) than in the sporadic group (37 years, range 25-46).
      All three patients with FAP-associated CMV-PTC had multicentric tumors, while all
      five sporadic patients did not. Our study found that approximately one-sixth of
      patients with CMV-PTC may have occult FAP. Patients with FAP-associated CMV-PTC
      appear to be younger and more likely to have multicentric tumors than those with
      sporadic CMV-PTC. Due to the increased risk of malignancy in patients with FAP,
      patients with CMV-PTC should be referred for colonoscopy and/or genetic
      evaluation for FAP.

PMID- 24934246
TI  - Systematic review and meta-analysis of health promotion interventions for
      children and adolescents using an ecological framework.
AB  - OBJECTIVE: To evaluate and quantify the evidence for health promotion
      interventions in children and adolescents. METHOD: 96 independent samples of
      smoking, physical activity, and diet studies were included. Outcomes included
      both objective and self-reports of health behavior, as well as proxy measures
      such as fitness. RESULTS: The aggregated effect was significant (g = .20, 95%
      confidence interval [CI] = 0.08-0.32, n = 96). A significant effect of
      intervention was observed at approximately 1-year follow-up (g = .07, 95% CI =
      0.02-0.14, n = 20). The greatest risk of bias was failure to blind outcome
      assessment, which occurred in 21% of studies. Most studies lacked sufficient
      detail to determine the quality of their randomization sequence (58%). Additional
      concerns about risk of bias for individual studies were minimal. Overall, the
      quality of this finding was moderate using the Grading of Recommendations
      Assessment, Development, and Evaluation criteria. CONCLUSION: Health promotion
      interventions are effective for modifying health behavior; however, effect sizes
      are small.

PMID- 24934248
TI  - Systematic review of psychological interventions for pediatric feeding problems.
AB  - OBJECTIVE: To conduct a systematic review of the research evaluating the effect
      of psychological interventions for pediatric feeding problems. METHODS: A search
      was conducted to identify studies using psychological interventions for pediatric
      feeding problems published between 1998 and 2013. Randomized controlled trials
      (RCTs) and nonrandomized studies that examined aggregated outcome data were
      included. Primary outcomes were child mealtime behavior, nutritional status, and
      caregiver stress. A risk of bias assessment was conducted and the quality of the
      evidence rated using Grading of Recommendations Assessment, Development, and
      Evaluation methodology. RESULTS: 13 studies were identified and a narrative
      synthesis framework was used to report findings. CONCLUSIONS: The preponderance
      of evidence suggests positive effects of psychological intervention for the
      treatment of feeding problems. However, limited data and the paucity of studies
      using RCT methodologies limit conclusions that can be drawn regarding the
      efficacy of these interventions. Future studies using more rigorous research
      methods are needed to enhance understanding of these interventions.

PMID- 24934247
TI  - Longitudinal trajectories of illness perceptions among adolescents with type 1
      diabetes.
AB  - OBJECTIVES: To examine development in illness perceptions of type 1 diabetes
      across adolescence and relationships with intelligence, diabetes responsibility,
      and diabetes outcomes. METHODS: Illness perceptions were measured via the Illness
      Perceptions Questionnaire at 3 times, every 6 months in 213 adolescents (M age =
      13.00; SD = 1.54) with type 1 diabetes. Intelligence and adolescents' perceived
      responsibility for diabetes were examined, and adolescents' report of adherence
      and quality of life (QOL), and glycosylated hemoglobin (HbA1c) from medical
      records addressed diabetes-related outcomes. RESULTS: Linear growth models showed
      significant increases in perceptions of diabetes coherence, chronicity,
      consequences, personal and treatment control, and decreases in diabetes
      cyclicality and parental control across time. More favorable illness perceptions
      were generally associated with adolescent intelligence at baseline, more
      adolescent responsibility for management, better adherence and QOL, and lower
      HbA1c at each time point. CONCLUSIONS: Results suggest that adolescents develop
      complex illness perceptions, which are associated with better diabetes
      management.

PMID- 24934249
TI  - On mentoring.

PMID- 24934250
TI  - Q & a session with Dr. Cooley.

PMID- 24934251
TI  - How we flipped the medical classroom.
AB  - Flipping the classroom centres on the delivery of print, audio or video based
      material prior to a lecture or class session. The class session is then dedicated
      to more active learning processes with application of knowledge through problem
      solving or case based scenarios. The rationale behind this approach is that
      teachers can spend their face-to-face time supporting students in deeper learning
      processes. In this paper we provide a background literature review on the flipped
      classroom along with a three step approach to flipping the classroom comprising
      implementing, enacting and evaluating this form of pedagogy. Our three step
      approach is based on actual experience of delivering a flipped classroom at the
      University of Hong Kong. This initiative was evaluated with positive results. We
      hope our experience will be transferable to other medical institutions.

PMID- 24934252
TI  - Hospital nurses' comfort in and frequency of delivering heart failure self-care
      education.
AB  - BACKGROUND: Nurses are expected to deliver pre-discharge heart failure education
      in 8 content areas: what heart failure means, medications, diet, activity, weight
      monitoring, fluid restriction, signs/symptoms of worsening condition and
      signs/symptoms of fluid overload. AIMS: To examine nurses' comfort in and
      frequency of delivering heart failure education to hospitalized patients.
      METHODS: A multicenter, descriptive, correlational design and questionnaire
      methods were used. General linear models were performed to assess associations of
      comfort in and frequency of delivering patient education after controlling for
      significant nurse characteristics. RESULTS: Of 118 nurses, mean age was 39 +/-
      11.6 years, 61.9% worked on cardiac units and 58.3% spent <15 min providing pre
      discharge heart failure education. Comfort in delivering education was highest
      for weight monitoring and lowest for activity, and was associated with nurse age
      (p=0.019), years in profession (p=0.004) and minutes providing pre-discharge
      education (p=0.003). Frequency delivering education was highest for
      signs/symptoms of worsening condition (mean frequency, 71.5% +/- 29%) and lowest
      for activity (42.7% +/- 29.4%) and was associated with comfort in educating
      patients (all p<0.001); and pre-discharge education minutes, p<0.001. Using
      general linear modeling, minutes spent delivering pre-discharge education
      remained associated with overall comfort in (p=0.04) and frequency of (p<0.001)
      heart failure education delivery. CONCLUSIONS: Nurses' comfort in and frequency
      of delivering education varied by heart failure self-care content area. Self-care
      education areas most important to survival and hospitalization had the lowest
      rates of nurse comfort and frequency. Systems and processes are needed to
      facilitate education delivery prior to hospital discharge.

PMID- 24934253
TI  - Evaluation of malignant breast lesions in the diagnostic setting with cone beam
      breast computed tomography (Breast CT): feasibility study.
AB  - To investigate the feasibility of noncontrast and contrast-enhanced cone beam
      breast Computed Tomography (CT) in demonstrating malignant breast lesions in the
      diagnostic setting. This Institutional Review Board approved, Health Information
      Portability and Accountability Act compliant, prospective study enrolled BI-RADS
      four and five patients from 2008 to 2010. Eighty-seven subjects had noncontrast
      breast CT, 42 had contrast-enhanced breast CT (CE-breast CT) with 70
      pathologically confirmed cancer diagnoses. All 70 comprise the study cohort for
      noncontrast breast CT, and 23 who had CE-breast CT comprise the cohort for CE
      breast CT. All had diagnostic work-up. Patient age, breast density, lesion size
      and characteristics, biopsy method, and core pathology were recorded. A Fisher's
      exact test was used to detect a difference in detectability. For agreement in
      size measurement between the imaging modalities, a paired t-test was employed.
      Reported p-values were based on 2-sided tests. Two one-sided tests were
      calculated to determine equivalence within +/-0.3 cm at a 90% significance level.
      Noncontrast breast CT identified 67 of 70 malignant lesions, detected by
      diagnostic work-up. CE-breast CT identified 23 of 23 index malignant lesions and
      in addition, found three malignant lesions in three cases not previously
      detected. Noncontrast breast CT demonstrated the index lesion in 67 of 70 cases
      and CE-breast CT demonstrated the index lesion in all 23 cases. An additional
      three new malignant lesions not seen with conventional diagnostic work-up were
      detected. In this preliminary study, breast CT with or without contrast was shown
      to be accurate at identifying malignant breast lesions in the diagnostic setting.

PMID- 24934254
TI  - Information and communication technology based prompting for treatment compliance
      for people with serious mental illness.
AB  - BACKGROUND: Non-compliance is a significant problem among people with serious
      mental disorders, presenting a challenge for mental health professionals. Prompts
      such as telephone calls, visits, and a posted referral letter to patients are
      currently used to encourage patient attendance at clinics and/or compliance with
      medication. More recently, the use of information and communication technology
      (ICT)-based prompting methods have increased. Methods include mobile text message
      (SMS - short message service), e-mail or use of any other electronic device with
      the stated purpose of encouraging compliance. OBJECTIVES: To investigate the
      effects of ICT-based prompting to support treatment compliance in people with
      serious mental illness compared with standard care. SEARCH METHODS: We searched
      the Cochrane Schizophrenia Group's Trials Register (31(st) May 2011 and 9(th)
      July 2012) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE,
      PubMed, MEDLINE, PsycINFO, and registries of clinical trials. Also, we inspected
      references of all identified studies for further trials and contacted authors of
      trials for additional information. SELECTION CRITERIA: Relevant randomised
      controlled trials involving adults with serious mental illness, comparing any ICT
      based prompt or combination of prompts by automatic or semi-automatic system
      compared with standard care. DATA COLLECTION AND ANALYSIS: Review authors
      reliably assessed trial quality and extracted data. We calculated risk ratio (RR)
      with 95% confidence intervals (CI) using a fixed-effect model. For continuous
      outcomes, we estimated the mean difference (MD) between groups, again with 95%
      confidence intervals. A 'Summary of findings' table using GRADE was created, and
      we assessed included studies for risk of bias. MAIN RESULTS: The search
      identified 35 references, with 25 studies, but we could only include two studies
      with a total of 358 participants. The studies had a moderate risk of bias, and
      therefore risk overestimating any positive effects of ICT-based prompting. Both
      included studies compared semi-automatised ICT-based prompting intervention with
      standard care groups in mental health outpatient care. The interventions were SMS
      message and an electronic assistant device. One included study reported our
      primary outcome, compliance.There was not any clear evidence that ICT-based
      prompts increase improvement in compliance (stop taking medication within six
      months n = 320, RR 1.11 CI 0.96 to 1.29, moderate quality evidence). There was
      some low quality evidence that ICT-based prompts have small effects for: mental
      state (average change in specific symptom scores within three months n = 251, MD 
      0.30 CI -0.53 to -0.07; severity of illness within three months n = 251, MD -0.10
      CI -0.13 to -0.07 and six months n = 251, MD -0.10 CI -0.13 to -0.07; average
      change in depressive scores within six months n = 251, RR 0.00 CI -0.28 to 0.28;
      global symptoms within three months n = 251, MD -0.10 CI -0.38 to -0.07; negative
      symptoms within three months n = 251, MD -0.10 CI -0.38 to 0.18 and six months n
      = 251, MD -0.30 CI -0.58 to 0.02, low quality evidence). Level of insight
      improved more among people receiving ICT-based prompt compared with those in the
      control group at six months (n = 251, MD -0.10 CI -0.13 to -0.07). ICT-based
      prompts also increased quality of life (average change in quality of life within
      six months n = 251, RR 0.50 CI 0.19 to 0.81, moderate quality evidence).Based on
      the existing data, there is no evidence that either intervention is less
      acceptable than the other (n = 347, 2 RCTs, RR 1.46 CI 0.70 to 3.05, low quality
      evidence). Included studies did not report outcomes of service utilisation,
      behaviour, costs or adverse events. AUTHORS' CONCLUSIONS: The evidence base on
      the effects of ICT-based prompts is still inconclusive. Data to clarify ICT-based
      prompting effects are awaited from an ongoing trial, but further well-conducted
      trials considering the different ICT-based prompts are warranted.

PMID- 24934255
TI  - "BeneFITs" to increase colorectal cancer screening in priority populations.

PMID- 24934258
TI  - Signaling pathways regulating red blood cell aggregation.
AB  - The exposure of red blood cells (RBC) to some hormones (epinephrine, insulin and
      glucagon) and agonists of alpha- and beta-adrenergic receptors (phenylephrine,
      clonidine and isoproterenol) may modify RBC aggregation (RBCA). Prostaglandin E1
      (PGE1) significantly decreased RBCA, and PGE2 had a similar but lesser effect.
      Adenylyl cyclase (AC) stimulator forskolin added to RBC suspension, caused a
      decrease of RBCA. More marked lowering of RBCA occurred after RBC treatment by dB
      cAMP. Phosphodiesterase (PDE) inhibitors markedly reduced RBCA. Ca2+ influx
      stimulated by A23187 was accompanied by an increase of RBCA. The blocking of Ca2+
      entry into the RBC by verapamil or the chelation of Ca2+ by EGTA led to a
      significant RBCA decrease. Lesser changes of aggregation were found after RBC
      incubation with protein kinase C stimulator phorbol 12-myristate 13-acetate
      (PMA). A significant inhibitory effect of tyrosine protein kinase (TPK) activator
      cisplatin on RBCA was revealed, while selective TPK inhibitor, lavendustin,
      eliminated the above mentioned effect. Taken together, the data demonstrate that
      changes in RBCA are connected with activation of different intracellular
      signaling pathways. We suggest that alterations in RBCA are mainly associated
      with the crosstalk between the adenylyl cyclase-cAMP system and Ca2+ control
      mechanisms. 

PMID- 24934259
TI  - Fluorescent Au(I)@Ag2/Ag3 giant cluster for selective sensing of mercury(II) ion.
AB  - Highly stable Au(I)(core)-Ag(0)(shell) particles have been synthesized in aqueous
      solution via a green chemistry pathway utilising sunlight irradiation. The shell
      of the particles is composed of fluorescent Ag2 and Ag3 clusters which make the
      large core-shell particles highly fluorescent. The Au(I) core of the particles
      offers long-term stability to the silver clusters, which are otherwise unstable
      in solution at room temperature, by the transfer of electron density from the
      shell. Successive additions of Hg(II) ions to the fluorescent solution cause
      efficient and selective quenching of the fluorescence with gradual red shifting
      of the emission peak. The metallophilic 5d(10)(Hg(2+))-4d(10)(Ag(delta+))
      interaction as well as Hg(II) stimulated aggregation have been ascribed to
      causing the fluorescence quenching and red shift. The fluorescent Au(I)(core)
      Ag(0)(shell) particles are a highly selective and sensitive sensing platform for
      the detection of Hg(II) down to 6 nM in the presence of various metal ions. The
      detection limit is far below the permissible level as determined by the EPA.
      Interferences due to Cu(II) and Fe(III) have been eliminated using Na2-EDTA and
      NH4HF2, respectively. The fluorescent particles are successfully transferred to
      various solvent systems making Hg(II) determination also possible in non-aqueous
      media. Finally, the temperature dependent fluorescence change with and without
      Hg(II) provides information about the metallophilic interaction.

PMID- 24934257
TI  - Factor XIII-A transglutaminase acts as a switch between preadipocyte
      proliferation and differentiation.
AB  - Factor XIII-A (FXIII-A) transglutaminase (TG) was recently identified as a
      potential causative obesity gene in human white adipose tissue (WAT). Here, we
      have examined the role of TG activity and the role of protein crosslinking in
      adipogenesis. Mouse WAT and preadipocytes showed abundant TG activity arising
      from FXIII-A. FXIII-A was localized to the cell surface and acted as a negative
      regulator of adipogenesis by promoting assembly of fibronectin (FN) from plasma
      into preadipocyte extracellular matrix. This modulated cytoskeletal dynamics and
      maintained the preadipocyte state. FXIII-A-assembled plasma FN (pFN) matrix
      promoted preadipocyte proliferation and potentiated the proproliferative effects
      of insulin (INS) while suppressing the prodifferentiating INS signaling. FXIII-A
      deficient mouse embryonic fibroblasts showed increased lipid accumulation and
      decreased proliferation as well as decreased pFN assembly into extracellular
      matrix. Thus, FXIII-A serves as a preadipocyte-bound
      proliferation/differentiation switch that mediates effects of hepatocyte-produced
      circulating pFN. 

PMID- 24934260
TI  - AuCd4: a Hume-Rothery Phase with VEC of 1.8 and icosahedral and trigonal
      prismatic clusters as building blocks.
AB  - The eta phase in the Au-Cd binary system has been synthesized, and the structure
      has been analyzed by single-crystal X-ray diffraction. The compound eta-AuCd(4)
      crystallizes in the hexagonal space group P6(3)/m (No. 176). The unit cell
      contains ~273 atoms. The compound AuCd(4) represents a ?3a * ?3a * c
      superstructure of the AgMg(4) type. The structure can be well described by
      icosahedral and trigonal-prismatic clusters. A phase transition to the high
      temperature epsilon phase occurs exothermically at around 578 K. The compound is
      formed at a sharp valence electron concentration of 1.8 e/a. The compound can be
      understood within the framework of the Hume-Rothery stabilization mechanism.

PMID- 24934256
TI  - A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic
      fibrosis is corrected by CFTR potentiator therapy.
AB  - Studies have endeavored to reconcile whether dysfunction of neutrophils in people
      with cystic fibrosis (CF) is a result of the genetic defect or is secondary due
      to infection and inflammation. In this study, we illustrate that disrupted
      function of the CF transmembrane conductance regulator (CFTR), such as that which
      occurs in patients with ?F508 and/or G551D mutations, correlates with impaired
      degranulation of antimicrobial proteins. We demonstrate that CF blood neutrophils
      release less secondary and tertiary granule components compared with control
      cells and that activation of the low-molecular-mass GTP-binding protein Rab27a,
      involved in the regulation of granule trafficking, is defective. The mechanism
      leading to impaired degranulation involves altered ion homeostasis caused by
      defective CFTR function with increased cytosolic levels of chloride and sodium,
      yet decreased magnesium measured in CF neutrophils. Decreased magnesium
      concentration in vivo and in vitro resulted in significantly decreased levels of
      GTP-bound Rab27a. Treatment of G551D patients with the ion channel potentiator
      ivacaftor resulted in normalized neutrophil cytosolic ion levels and activation
      of Rab27a, thereby leading to increased degranulation and bacterial killing. Our
      results confirm that intrinsic alterations of circulating neutrophils from
      patients with CF are corrected by ivacaftor, thus illustrating additional
      clinical benefits for CFTR modulator therapy. 

PMID- 24934261
TI  - Repeated cycles of chemical and physical disinfection and their influence on
      Mycobacterium avium subsp. paratuberculosis viability measured by propidium
      monoazide F57 quantitative real time PCR.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) has a high degree of resistance
      to chemical and physical procedures frequently used for the elimination of other
      bacteria. Recently, a method for the determination of viability by exposure of
      MAP to propidium monoazide (PMA) and subsequent real time quantitative PCR (qPCR)
      was established and found to be comparable with culture. The aim of this study
      was to apply the PMA qPCR method to determine the impact of increasing
      concentration or time and repeated cycles of the application of selected
      disinfectants on MAP viability. Different MAP isolates responded to the same type
      of stress in different ways. The laboratory strain CAPM 6381 had the highest
      tolerance, while the 8819 low-passage field isolate was the most sensitive.
      Ultraviolet exposure caused only a partial reduction in MAP viability; all MAP
      isolates were relatively resistant to chlorine. Only the application of peracetic
      acid led to the total elimination of MAP. Repeated application of the treatments
      resulted in more significant decreases in MAP viability compared to single
      increases in the concentration or time of exposure to the disinfectant.

PMID- 24934262
TI  - Infectious diseases in large-scale cat hoarding investigations.
AB  - Animal hoarders accumulate animals in over-crowded conditions without adequate
      nutrition, sanitation, and veterinary care. As a result, animals rescued from
      hoarding frequently have a variety of medical conditions including respiratory
      infections, gastrointestinal disease, parasitism, malnutrition, and other
      evidence of neglect. The purpose of this study was to characterize the infectious
      diseases carried by clinically affected cats and to determine the prevalence of
      retroviral infections among cats in large-scale cat hoarding investigations.
      Records were reviewed retrospectively from four large-scale seizures of cats from
      failed sanctuaries from November 2009 through March 2012. The number of cats
      seized in each case ranged from 387 to 697. Cats were screened for feline
      leukemia virus (FeLV) and feline immunodeficiency virus (FIV) in all four cases
      and for dermatophytosis in one case. A subset of cats exhibiting signs of upper
      respiratory disease or diarrhea had been tested for infections by PCR and fecal
      flotation for treatment planning. Mycoplasma felis (78%), calicivirus (78%), and
      Streptococcus equi subspecies zooepidemicus (55%) were the most common
      respiratory infections. Feline enteric coronavirus (88%), Giardia (56%),
      Clostridium perfringens (49%), and Tritrichomonas foetus (39%) were most common
      in cats with diarrhea. The seroprevalence of FeLV and FIV were 8% and 8%,
      respectively. In the one case in which cats with lesions suspicious for
      dermatophytosis were cultured for Microsporum canis, 69/76 lesional cats were
      culture-positive; of these, half were believed to be truly infected and half were
      believed to be fomite carriers. Cats from large-scale hoarding cases had high
      risk for enteric and respiratory infections, retroviruses, and dermatophytosis.
      Case responders should be prepared for mass treatment of infectious diseases and
      should implement protocols to prevent transmission of feline or zoonotic
      infections during the emergency response and when transferring the rescued cats
      to other shelters or to adopters.

PMID- 24934263
TI  - Feline infectious diseases: our curiosity could be their salvation. Introduction.

PMID- 24934264
TI  - Transformation of curcumin from food additive to multifunctional medicine:
      nanotechnology bridging the gap.
AB  - Curcumin (CUR) is a yellow-coloured polyphenolic compound obtained from the
      rhizomes of Curcuma longa. In-depth pharmacological screening of curcumin has
      given the evidence that CUR persuades shielding and curative effects against
      various cancers, cardiovascular, wound healing effect and neuro disorders etc
      owning to anti-oxidant, antiproliferative, anti-inflammatory, anti-angiogenic and
      antimicrobial activities. However, miserable bioavailability due to poor aqueous
      solubility limits the application of CUR in various ailments. Different
      methodologies including the nanoparticle technology have been reported for the
      bioavailability enhancement of CUR. Nanoparticles exhibit not only the
      improvement in the solubility of CUR and alike lipophilic molecules (resulted in
      improved bioavailability) but also giving the opportunity for the disease
      specific cellular and organ targeting. Improved bioavailability and disease based
      site specific delivery of CUR is more likely to bring it as a safe
      multifunctional medicine. 

PMID- 24934265
TI  - Covalent, sequence-specific attachment of long DNA molecules to a surface using
      DNA-templated click chemistry.
AB  - We present a novel method that covalently and sequence-specifically attaches long
      DNA molecules to a surface that is compatible with high-resolution atomic force
      microscopy (AFM) imaging. Surfaces prepared with this approach are ideally suited
      for performing biophysical experiments on single DNA molecules. 

PMID- 24934266
TI  - Hydrophobically-associating cationic polymers as micro-bubble surface modifiers
      in dissolved air flotation for cyanobacteria cell separation.
AB  - Dissolved air flotation (DAF), an effective treatment method for clarifying
      algae/cyanobacteria-laden water, is highly dependent on coagulation-flocculation.
      Treatment of algae can be problematic due to unpredictable coagulant demand
      during blooms. To eliminate the need for coagulation-flocculation, the use of
      commercial polymers or surfactants to alter bubble charge in DAF has shown
      potential, termed the PosiDAF process. When using surfactants, poor removal was
      obtained but good bubble adherence was observed. Conversely, when using polymers,
      effective cell removal was obtained, attributed to polymer bridging, but polymers
      did not adhere well to the bubble surface, resulting in a cationic clarified
      effluent that was indicative of high polymer concentrations. In order to combine
      the attributes of both polymers (bridging ability) and surfactants
      (hydrophobicity), in this study, a commercially-available cationic polymer,
      poly(dimethylaminoethyl methacrylate) (polyDMAEMA), was functionalised with
      hydrophobic pendant groups of various carbon chain lengths to improve adherence
      of polymer to a bubble surface. Its performance in PosiDAF was contrasted against
      commercially-available poly(diallyl dimethyl ammonium chloride) (polyDADMAC). All
      synthesised polymers used for bubble surface modification were found to produce
      positively charged bubbles. When applying these cationic micro-bubbles in
      PosiDAF, in the absence of coagulation-flocculation, cell removals in excess of
      90% were obtained, reaching a maximum of 99% cell removal and thus demonstrating
      process viability. Of the synthesised polymers, the polymer containing the
      largest hydrophobic functionality resulted in highly anionic treated effluent,
      suggesting stronger adherence of polymers to bubble surfaces and reduced residual
      polymer concentrations. 

PMID- 24934268
TI  - Sodium-cutting: a new top-down approach to cut open nanostructures on nonplanar
      surfaces on a large scale.
AB  - We report a new, low-cost and simple top-down approach, "sodium-cutting", to cut
      and open nanostructures deposited on a nonplanar surface on a large scale. The
      feasibility of sodium-cutting was demonstrated with the successfully cutting open
      of ~100% carbon nanospheres into nanobowls on a large scale from Sn@C nanospheres
      for the first time. 

PMID- 24934267
TI  - Column studies to assess the effects of climate variables on redox processes
      during riverbank filtration.
AB  - Riverbank filtration is an established technique used world-wide to produce clean
      drinking water in a reliable and cost-efficient way. This practice is, however,
      facing new challenges posed by climate change, as already observed during past
      heat waves with the local occurrence of anoxic conditions. In this study we
      investigated the effect of direct (temperature) and indirect (dissolved organic
      matter (DOM) concentration and composition, flow rate) climate change variables
      on redox processes (aerobic respiration, denitrification and Mn(III/IV)/Fe(III)
      reduction) by means of column experiments. Natural river water, modified river
      water and river water mixed with treated wastewater effluent were used as feed
      waters for the columns filled with natural sand from a river-infiltration system
      in Switzerland. Biodegradable dissolved organic matter was mainly removed
      immediately at the column inlet and particulate organic matter (POM) associated
      with the natural sand was the main electron donor for aerobic respiration
      throughout the column. Low infiltration rates (<=0.01 m/h) enhanced the oxygen
      consumption leading to anoxic conditions. DOM consumption did not seem to be
      sensitive to temperature, although oxygen consumption (i.e., associated with POM
      degradation) showed a strong temperature dependence with an activation energy of
      ~70 kJmol(-1). Anoxic conditions developed at 30  degrees C with partial
      denitrification and formation of nitrite and ammonium. In absence of oxygen and
      nitrate, Mn(II) was mobilized at 20  degrees C, highlighting the importance of
      nitrate acting as a redox buffer under anoxic conditions preventing the reductive
      dissolution of Mn(III/IV)(hydr)oxides. Reductive dissolution of
      Fe(III)(hydr)oxides was not observed under these conditions.

PMID- 24934269
TI  - A Wavelet-Statistical Features Approach for Nonconvulsive Seizure Detection.
AB  - The detection of nonconvulsive seizures (NCSz) is a challenge because of the lack
      of physical symptoms, which may delay the diagnosis of the disease. Many
      researchers have reported automatic detection of seizures. However, few
      investigators have concentrated on detection of NCSz. This article proposes a
      method for reliable detection of NCSz. The electroencephalography (EEG) signal is
      usually contaminated by various nonstationary noises. Signal denoising is an
      important preprocessing step in the analysis of such signals. In this study, a
      new wavelet-based denoising approach using cubical thresholding has been proposed
      to reduce noise from the EEG signal prior to analysis. Three statistical features
      were extracted from wavelet frequency bands, encompassing the frequency range of
      0 to 8, 8 to 16, 16 to 32, and 0 to 32 Hz. Extracted features were used to train
      linear classifier to discriminate between normal and seizure EEGs. The
      performance of the method was tested on a database of nine patients with 24
      seizures in 80 hours of EEG recording. All the seizures were successfully
      detected, and false positive rate was found to be 0.7 per hour.

PMID- 24934270
TI  - A comparison of the discursive practices of perception of patient participation
      in haemodialysis units.
AB  - BACKGROUND: According to Norwegian law, nurses are obligated to provide an
      acceptable level of health assistance to patients and their family members and to
      allow patients and their family members to participate in the planning of patient
      care and treatment. AIM: The aim of this study is to compare the perceptions of
      older patients undergoing haemodialysis treatment and of their next of kin and of
      nurses regarding patient participation in the context of haemodialysis treatment.
      RESEARCH DESIGN: The study adopts an approach that is both comparative and
      explorative in nature by examining the narratives of patients, nurses and next of
      kin and by performing critical discourse analysis as outlined by Fairclough.
      ETHICAL CONSIDERATIONS: Permission to carry out the research was granted by the
      Regional Committee for Medical and Health Research Ethics of Mid-Norway and by
      the participating hospitals. Informed consent and confidentiality were ensured.
      FINDINGS: Two discourses were found: (a) the discourse of paternalism with the
      discursive practices of achieving physiological balance in patients, trusting the
      healthcare team and being excluded or included in the difficult end-of-life
      decision-making process, and (b) the discourse of patient participation, with the
      themes of maintaining patients' quality of life and trusting patients.
      CONCLUSION: The participation of older patients and their next of kin was not as
      well integrated as social practice in dialysis units. The dominant discourse
      seemed to have an ideology and social practice of paternalism. However, there
      existed hegemonic struggles for an ideology of patient participation that
      involved (a) achieving physiological balance in patients versus maintaining
      patients' quality of life, (b) trusting the healthcare team versus trusting the
      patient, and (c) being excluded versus included in the difficult end-of-life
      decision-making process.

PMID- 24934271
TI  - Empathy in Brazilian nursing professionals: a descriptive study.
AB  - BACKGROUND: Essential for the help relation, empathy is the ability to
      understand, share, and perceive the subjective experience of other human beings.
      OBJECTIVE: The objective in this non-experimental, exploratory, and descriptive
      research was to verify, observe, and document empathy in nursing professionals.
      RESEARCH DESIGN: Non-experimental, exploratory, and descriptive research.
      Participants and research context: the study was conducted at two large
      hospitals, one public and the other private, across all shifts. The sample
      included 159 individuals. A questionnaire was used to identify sociodemographic
      characteristics and the empathy inventory was applied. ETHICAL CONSIDERATIONS:
      This study received approval from the Research Ethics Committee at the University
      of Sao Paulo at Ribeirao Preto College of Nursing, opinion 1348/2011, and
      authorization from the health institutions involved. FINDINGS: The association
      tests demonstrated that professionals working in the night shift and in a work
      scale rotation scheme, older professionals, and professionals with longer
      professional experience are less empathetic. On the other hand, professionals
      working in the day shift and in a single shift are more empathetic. Other
      influential factors are the time on the job, education, and work shift.
      CONCLUSION: There is a lack of empathy studies in professional practice contexts,
      in human resource development programs, and throughout the professional education
      process.

PMID- 24934273
TI  - Induction of phenotypic plasticity in rattlesnake trophic morphology by diet
      manipulation.
AB  - Gape-limited predators are restricted in the shape and size of prey items they
      can ingest by their trophic morphology. Evolutionary theory predicts that gape
      limited predators, such as rattlesnakes, should possess plasticity in their
      trophic morphology to allow them to respond to environmental cues about their
      prey base. This study examined the effects of two possible influences over
      trophic morphology in the pit-viper Crotalus viridis viridis. Snakes from six
      litters were exposed to diet manipulations performed over 480 days. By day 480,
      snakes from two prey-size treatments exhibited significantly different head
      shapes. Snakes reared on whole rodents had broader heads, whereas snakes force
      fed homogenized prey had narrower heads. Shape differences varied among litters,
      suggesting that not all litters responded the same to diet manipulations. Results
      suggest that trophic morphology of rattlesnakes is plastic, at least in some
      litters, and can be induced by prey items.

PMID- 24934272
TI  - Blood folate concentrations among women of childbearing age by race/ethnicity and
      acculturation, NHANES 2001-2010.
AB  - Hispanic women have higher rates of neural tube defects and report lower total
      folic acid intakes than non-Hispanic white (NHW) women. Total folic acid intake,
      which is associated with neural tube defect risk reduction, has been found to
      vary by acculturation factors (i.e. language preference, country of origin, or
      time spent in the United States) among Hispanic women. It is unknown whether this
      same association is present for blood folate status. The objective of this
      research was to assess the differences in serum and red blood cell (RBC) folate
      concentrations between NHW women and Mexican American (MA) women and among MA
      women by acculturation factors. Cross-sectional data from the 2001-2010 National
      Health and Nutrition Examination Survey (NHANES) were used to investigate how
      blood folate concentrations differ among NHW or MA women of childbearing age. The
      impact of folic acid supplement use on blood folate concentrations was also
      examined. MA women with lower acculturation factors had lower serum and RBC
      folate concentrations compared with NHW women and to their more acculturated MA
      counterparts. Consuming a folic acid supplement can minimize these disparities,
      but MA women, especially lower acculturated MA women, were less likely to report
      using supplements. Public health efforts to increase blood folate concentrations
      among MA women should consider acculturation factors when identifying appropriate
      interventions. 

PMID- 24934274
TI  - Future treatment in patients with chronic obstructive pulmonary disease: to
      reverse or not to reverse steroid resistance-that is the question.

PMID- 24934275
TI  - Early improvement in basophil sensitivity predicts symptom relief with grass
      pollen immunotherapy.

PMID- 24934277
TI  - Unemployment and Suicide Mortality: Evidence from Regional Panel Data in Europe.
AB  - This paper addresses the influence of economic activity on suicide mortality in
      Europe. To this end, it employs a new panel data set of 275 regions in 29
      countries over the period 1999-2010. The results suggest that unemployment does
      have a significantly positive influence on suicides. In line with economic
      theory, this influence varies among gender and age groups. Men of working age are
      particularly sensitive, while old-age suicide mortality (older than 65 years old)
      hardly responds to unemployment. Moreover, real economic growth negatively
      affects the suicide rates of working-age men. The results withstand several
      robustness checks, such as sample variations, and after controlling for serial
      and spatial autocorrelation.

PMID- 24934278
TI  - CuGeO3 nanowires covered with graphene as anode materials of lithium ion
      batteries with enhanced reversible capacity and cyclic performance.
AB  - A facile one-step route was developed to synthesize crystalline CuGeO3
      nanowire/graphene composites (CGCs). Crystalline CuGeO3 nanowires were tightly
      covered and anchored by graphene sheets, forming a layered structure.
      Subsequently, CGCs were exploited as electrode materials for lithium ion
      batteries (LIBs). The reversible formation of Li2O buffer layer and elastic
      graphene sheets accommodated the volume change during the charge and discharge
      processes. CGC containing 37 wt% graphene exhibited a superior electrochemical
      performance, that is, a remarkable reversible capacity (1265 mA h g(-1) for the
      first cycle), an outstanding cyclic performance (853 mA h g(-1) after 50 cycles
      under a current density of 200 mA g(-1)), a high coulombic efficiency, and an
      excellent rate capability. Clearly, CGCs may stand out as a promising anode
      material for LIBs.

PMID- 24934279
TI  - TrkB is involved in the mechanism by which BDNF accelerates the glutamate-induced
      death of rat neuroblastoma B35 cells.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) binds to its high-affinity
      binding receptor, tropomyosin-related kinase (Trk) B, and can induce neuronal
      differentiation and survival. BDNF also accelerates neuronal cell death in a
      glutamate-induced model; however, it has been unknown whether the mechanism
      involves TrkB. In the current study, to determine the role of TrkB in neuronal
      cell death, we investigated TrkB involvement in BDNF acceleration of glutamate
      induced neuronal death. METHODS: A TrkB-stable transformant of rat neuroblastoma
      B35 (B35(TrkB)) cells was utilized to investigate whether TrkB is involved in
      BDNF acceleration of neuronal death. The cell viability of the B35(TrkB) cells
      was compared to that of mock vector-transgened B35 (B35(mock)) cells after
      treatment with/without BDNF and glutamate. RESULTS: In both B35(TrkB) and
      B35(mock) cells, glutamate treatment decreased the cell viability. BDNF treatment
      further accelerated the decrease in the viability of B35(TrkB) cells, but not
      that in the viability of B35(mock) cells. At glutamate concentrations that did
      not significantly decrease cell viability, BDNF increased the cell viability of
      B35(TrkB), but not that of B35(mock). A mitogen-activated protein kinase (MAPK)
      inhibitor, U0126, suppressed BDNF's accelerating effect on cell death. Although
      B35 parental cells endogenously express other neurotrophin receptors such as
      TrkA, nerve growth factor beta (a ligand of TrkA and p75(NTR)) could not
      influence the viability of B35(TrkB) or B35(mock) cells. CONCLUSION: These
      results indicate that TrkB is an intermediator for the trophic and toxicity
      exacerbating effects of BDNF against cell viabilities at non-cytotoxic and
      cytotoxic glutamate concentrations, respectively.

PMID- 24934276
TI  - A genome-wide survey of CD4(+) lymphocyte regulatory genetic variants identifies
      novel asthma genes.
AB  - BACKGROUND: Genome-wide association studies have yet to identify the majority of
      genetic variants involved in asthma. We hypothesized that expression quantitative
      trait locus (eQTL) mapping can identify novel asthma genes by enabling
      prioritization of putative functional variants for association testing.
      OBJECTIVE: We evaluated 6706 cis-acting expression-associated variants (eSNPs)
      identified through a genome-wide eQTL survey of CD4(+) lymphocytes for
      association with asthma. METHODS: eSNPs were tested for association with asthma
      in 359 asthmatic patients and 846 control subjects from the Childhood Asthma
      Management Program, with verification by using family-based testing. Significant
      associations were tested for replication in 579 parent-child trios with asthma
      from Costa Rica. Further functional validation was performed by using
      formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR
      and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas
      2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes.
      RESULTS: Cis-acting eSNPs demonstrated associations with asthma in both cohorts.
      We confirmed the previously reported association of ORMDL3/GSDMB variants with
      asthma (combined P = 2.9 * 10(-8)). Reproducible associations were also observed
      for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N
      acetyl-alpha-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P
      = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+)
      lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA
      segments with histone modifications that denote open chromatin status and confer
      enhancer activity. CONCLUSIONS: Our results demonstrate the utility of eQTL
      mapping in the identification of novel asthma genes and provide evidence for the
      importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.

PMID- 24934280
TI  - It's time for a practical method quantifying vascular calcification.

PMID- 24934281
TI  - Lymphoma.

PMID- 24934282
TI  - Proximal median neuropathy caused by surgical manipulation of Masson tumor.

PMID- 24934283
TI  - Congenital abnormalities and hepatoblastoma: a report from the Children's
      Oncology Group (COG) and the Utah Population Database (UPDB).
AB  - Beckwith-Wiedemann Syndrome (BWS) and familial adenomatous polyposis (FAP) are
      known to predispose to hepatoblastoma (HB). A case-control study was conducted
      through the Children's Oncology Group (COG) to study the association of HB with
      isolated congenital abnormalities. Cases (N = 383) were diagnosed between 2000
      and 2008. Controls (N = 387) were recruited from state birth registries,
      frequency matched for sex, region, year of birth, and birth weight. Data on
      congenital abnormalities among subjects and covariates were obtained by maternal
      telephone interview. Odds ratios (OR) and 95% confidence intervals (CI)
      describing the association between congenital abnormalities with HB, adjusted for
      sex, birth weight, maternal age and maternal education, were calculated using
      unconditional logistic regression. There was a significant association of HB with
      kidney, bladder, or sex organ abnormalities (OR = 4.75; 95% CI: 1.74-13) which
      appeared to be specific to kidney/bladder defects (OR = 4.3; 95% CI: 1.2-15.3)
      but not those of sex organs (OR = 1.24; 95% CI: 0.37-4.1). Elevated but non
      significant ORs were found for spina bifida or other spinal defects (OR = 2.12;
      95% CI: 0.39-11.7), large or multiple birthmarks (OR = 1.33; 95% CI: 0.81-2.21).
      The results were validated through the Utah Population Database (UPDB), a
      statewide population-based registry linking birth certificates, medical records,
      and cancer diagnoses. In the UPDB, there were 29 cases and 290 population
      controls matched 10:1 on sex and birth year. Consistent with the COG findings,
      kidney/bladder defects were associated with hepatoblastoma. These results confirm
      the association of HB with kidney/bladder abnormalities.

PMID- 24934284
TI  - Co-development of pyogenic granuloma and capillary hemangioma on the alveolar
      ridge associated with a dental implant: a case report.
AB  - INTRODUCTION: The development of various benign oral mucosal lesions associated
      with dental implants, such as pyogenic granuloma or peripheral giant cell
      granuloma, has been rarely reported. However, the occurrence of vascular
      diseases, such as hemangioma, related to dental implants has not been explored in
      the literature. In this study, we report a case of co-development of pyogenic
      granuloma and capillary hemangioma on the alveolar ridge associated with a dental
      implant in a patient undergoing antithrombotic therapy. To the best of our
      knowledge, this is first case of hemangioma formation associated with a dental
      implant. CASE PRESENTATION: A 68-year-old Korean man was referred for
      intermittent bleeding and a dome-shaped overgrowing mass on his upper alveolar
      ridge. He underwent dental implantation 5 years ago, and was started on warfarin
      for cerebral infarction a year ago. He had experienced gum bleeding and gingival
      mass formation 6 months after warfarinization; then, his implant fixture was
      removed. However, his gingival mass has been gradually increasing. The gingival
      mass was surgically excised, and revealed the coexistence of pyogenic granuloma
      and capillary hemangioma in histological analysis of the specimen. The lesion has
      showed no recurrence for more than a year. CONCLUSIONS: Regarding immunostaining
      features, the endothelial cell markers, CD34 and CD31, and the mesenchymal cell
      marker, vimentin, were strongly detected, but cell proliferation marker, Ki-67,
      was negatively expressed in the endothelial cells of the hemangioma portion.
      However, in the pyogenic granuloma portion, CD34 was almost negatively detected,
      whereas vimentin and Ki-67 were highly detected in the fibroblast-like tumor
      cells. According to these heterogeneous characteristics of the lesion, the
      patient was diagnosed with coexistence of pyogenic granuloma and capillary
      hemangioma associated with the dental implant on the attached gingiva. We
      recommend that patients with dental implants who have chronic peri-implantitis
      under antithrombotic therapy should be closely followed to ensure early detection
      of oral mucosal abnormalities.

PMID- 24934285
TI  - Elevated serum uric acid is associated with angiotensinogen in obese patients
      with untreated hypertension.
AB  - This study investigated the correlation between elevated serum uric acid (SUA)
      and angiotensinogen in obesity patients with hypertension. A total of 162 obese
      and 162 nonobese men with hypertension were recruited in this study. Plasma
      angiotensinogen levels were measured by enzyme-linked immunosorbent assay.
      Fasting insulin (FINS) was evaluated by radioimmunoassay. Compared with nonobese
      patients, obese patients exhibited higher levels of angiotensinogen, FINS, and
      homeostasis model assessment index-insulin resistance (HOMA-IR) (P<.001 for all).
      Moreover, these indexes significantly increased in obese patients in the highest
      tertile of SUA when compared with those in the lowest tertile of SUA (P<.001,
      P=.002, P=.007, respectively). In the obese group, SUA levels were significantly
      related to angiotensinogen, FINS, and HOMA-IR, respectively. Furthermore, it was
      demonstrated that obesity * uric acid was an independent contributor to
      angiotensinogen (beta=0.257, P<.001). In conclusion, elevated SUA is strongly
      related to angiotensinogen in an obesity-dependent manner in hypertension.

PMID- 24934286
TI  - Sexual dimorphism in biomedical research: a call to analyse by sex.

PMID- 24934290
TI  - Bariatric surgery - effects on obesity and related co-morbidities.
AB  - Laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric
      bypass (RYGB) and laparoscopic sleeve gastrectomy (SG) are the three most
      commonly performed bariatric procedures. Obesity responds well to bariatric
      surgery, with major long-lasting weight loss that is most pronounced after RYGB
      and SG, where the mean weight loss is about 40 kg or 15 body mass index (BMI)
      units. Some of the benefits after RYGB and SG are independent of weight loss, and
      the remission of type 2 diabetes is observed a few days after the operation; this
      depends on changes in insulin sensitivity and gut hormone responses, especially a
      10-fold increase in glucagon-like peptide-1 (GLP-1), which improves insulin
      secretion. After gastric banding, the remission of diabetes depends more on
      weight loss. Bariatric surgery reduces cardiovascular risk factors including
      hypertension, lipid disturbances, non-alcoholic fatty liver, musculoskeletal pain
      and reduces mortality of diabetes, cardiovascular diseases and cancers. Bariatric
      surgery also improves quality of life. The acute complications of surgery are
      infection, bleeding and anastomotic leak. Long-term complications are nutritional
      deficiencies, including vitamins and minerals, and anemia. Some patients have
      dumping after meals, and a few patients will develop postprandial hypoglycemia
      after RYGB. About 25% of patients require plastic surgery to provide relief from
      excessive skin tissue. 

PMID- 24934288
TI  - Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra
      dopamine neurons.
AB  - Dopamine midbrain neurons within the substantia nigra are particularly prone to
      degeneration in Parkinson's disease. Their selective loss causes the major motor
      symptoms of Parkinson's disease, but the causes for the high vulnerability of SN
      DA neurons, compared to neighbouring, more resistant ventral tegmental area
      dopamine neurons, are still unclear. Consequently, there is still no cure
      available for Parkinson's disease. Current therapies compensate the progressive
      loss of dopamine by administering its precursor l-DOPA and/or dopamine D2
      receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca(2+) channels
      both contribute to Parkinson's disease pathology. L-type Ca(2+) channel blockers
      protect SN DA neurons from degeneration in Parkinson's disease and its mouse
      models, and they are in clinical trials for neuroprotective Parkinson's disease
      therapy. However, their physiological functions in SN DA neurons remain unclear.
      D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a
      negative feedback loop through activation of G-protein coupled potassium channels
      (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing
      somatodendritic D2-autoreceptor responses that show pronounced desensitization in
      PARK-gene Parkinson's disease mouse models. We analysed surviving human SN DA
      neurons from patients with Parkinson's disease and from controls, and detected
      elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson's
      disease. By electrophysiological analysis of postnatal juvenile and adult mouse
      SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor
      desensitization is reduced with postnatal maturation. Furthermore, a transient
      high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine,
      induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in
      juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With
      pharmacological and genetic tools, we identified that the expression of this
      sensitized D2-autoreceptor phenotype required Cav1.3 L-type Ca(2+) channel
      activity, internal Ca(2+), and the interaction of the neuronal calcium sensor NCS
      1 with D2-autoreceptors. Thus, we identified a first physiological function of
      Cav1.3 L-type Ca(2+) channels in SN DA neurons for homeostatic modulation of
      their D2-autoreceptor responses. L-type Ca(2+) channel activity however, was not
      important for pacemaker activity of mouse SN DA neurons. Furthermore, we detected
      elevated substantia nigra dopamine messenger RNA levels of NCS-1 (but not Cav1.2
      or Cav1.3) after cocaine in mice, as well as in remaining human SN DA neurons in
      Parkinson's disease. Thus, our findings provide a novel homeostatic functional
      link in SN DA neurons between Cav1.3- L-type-Ca(2+) channels and D2-autoreceptor
      activity, controlled by NCS-1, and indicate that this adaptive signalling network
      (Cav1.3/NCS-1/D2/GIRK2) is also active in human SN DA neurons, and contributes to
      Parkinson's disease pathology. As it is accessible to pharmacological modulation,
      it provides a novel promising target for tuning substantia nigra dopamine neuron
      activity, and their vulnerability to degeneration. 

PMID- 24934291
TI  - Bioinspired multicompartmental microfibers from microfluidics.
AB  - Bioinspired multicompartmental microfibers are generated by novel capillary
      microfluidics. The resultant microfibers possess multicompartment body-and-shell
      compositions with specifically designed geometries. Potential use of these
      microfibers for tissue-engineering applications is demonstrated by creating
      multifunctional fibers with a spatially controlled encapsulation of cells. 

PMID- 24934292
TI  - Semantic trouble sources and their repair in conversations affected by
      Parkinson's disease.
AB  - BACKGROUND: It is known that dysarthria arising from Parkinson's disease may
      affect intelligibility in conversational interaction. Research has also shown
      that Parkinson's disease may affect cognition and cause word-retrieval
      difficulties and pragmatic problems in the use of language. However, it is not
      known whether or how these problems become manifest in everyday conversations or
      how conversation partners handle such problems. AIMS: To describe the pragmatic
      problems related to the use of words that occur in everyday conversational
      interaction in dyads including an individual with Parkinson's disease, and to
      explore how interactants in conversation handle the problems to re-establish
      mutual understanding. METHODS & PROCEDURES: Twelve video-recorded everyday
      conversations involving three couples where one of the individuals had
      Parkinson's disease were included in the study. All instances of other-initiated
      repair following a contribution from the people with Parkinson's disease were
      analysed. Those instances involving a trouble source relating to the use of words
      were analysed with a qualitative interaction analysis based on the principles of
      conversation analysis. OUTCOMES & RESULTS: In 70% of the instances of other
      initiated repair the trouble source could be related to the semantic content
      produced by the individual with Parkinson's disease. The problematic
      contributions were typically characterized by more or less explicit symptoms of
      word search or use of atypical wording. The conversation partners completed the
      repair work collaboratively, but typically the non-impaired individual made a
      rephrasing or provided a suggestion for what the intended meaning had been.
      CONCLUSIONS & IMPLICATIONS: In clinical work with people with Parkinson's disease
      and their conversation partners it is important to establish what type of trouble
      sources occur in conversations in a specific dyad. It may often be necessary to
      look beyond intelligibility and into aspects of pragmatics to understand more
      fully the impact of Parkinson's disease on everyday conversational interaction.

PMID- 24934293
TI  - Effective cluster typical medium theory for the diagonal Anderson disorder model
      in one- and two-dimensions.
AB  - We develop a cluster typical medium theory to study localization in disordered
      electronic systems. Our formalism is able to incorporate non-local correlations
      beyond the local typical medium theory in a systematic way. The cluster typical
      medium theory utilizes the momentum-resolved typical density of states and
      hybridization function to characterize the localization transition. We apply the
      formalism to the Anderson model of localization in one- and two-dimensions. In
      one-dimension, we find that the critical disorder strength scales inversely with
      the linear cluster size with a power law, Wc ~ (1/Lc)(1/nu), whereas in two
      dimensions, the critical disorder strength decreases logarithmically with the
      linear cluster size. Our results are consistent with previous numerical work and
      are in agreement with the one-parameter scaling theory. 

PMID- 24934289
TI  - A mitochondrial origin for frontotemporal dementia and amyotrophic lateral
      sclerosis through CHCHD10 involvement.
AB  - Mitochondrial DNA instability disorders are responsible for a large clinical
      spectrum, among which amyotrophic lateral sclerosis-like symptoms and
      frontotemporal dementia are extremely rare. We report a large family with a late
      onset phenotype including motor neuron disease, cognitive decline resembling
      frontotemporal dementia, cerebellar ataxia and myopathy. In all patients, muscle
      biopsy showed ragged-red and cytochrome c oxidase-negative fibres with combined
      respiratory chain deficiency and abnormal assembly of complex V. The multiple
      mitochondrial DNA deletions found in skeletal muscle revealed a mitochondrial DNA
      instability disorder. Patient fibroblasts present with respiratory chain
      deficiency, mitochondrial ultrastructural alterations and fragmentation of the
      mitochondrial network. Interestingly, expression of matrix-targeted
      photoactivatable GFP showed that mitochondrial fusion was not inhibited in
      patient fibroblasts. Using whole-exome sequencing we identified a missense
      mutation (c.176C>T; p.Ser59Leu) in the CHCHD10 gene that encodes a coiled-coil
      helix coiled-coil helix protein, whose function is unknown. We show that CHCHD10
      is a mitochondrial protein located in the intermembrane space and enriched at
      cristae junctions. Overexpression of a CHCHD10 mutant allele in HeLa cells led to
      fragmentation of the mitochondrial network and ultrastructural major
      abnormalities including loss, disorganization and dilatation of cristae. The
      observation of a frontotemporal dementia-amyotrophic lateral sclerosis phenotype
      in a mitochondrial disease led us to analyse CHCHD10 in a cohort of 21 families
      with pathologically proven frontotemporal dementia-amyotrophic lateral sclerosis.
      We identified the same missense p.Ser59Leu mutation in one of these families.
      This work opens a novel field to explore the pathogenesis of the frontotemporal
      dementia-amyotrophic lateral sclerosis clinical spectrum by showing that
      mitochondrial disease may be at the origin of some of these phenotypes. 

PMID- 24934294
TI  - The ITALK project: a developmental robotics approach to the study of individual,
      social, and linguistic learning.
AB  - This article presents results from a multidisciplinary research project on the
      integration and transfer of language knowledge into robots as an empirical
      paradigm for the study of language development in both humans and humanoid
      robots. Within the framework of human linguistic and cognitive development, we
      focus on how three central types of learning interact and co-develop: individual
      learning about one's own embodiment and the environment, social learning
      (learning from others), and learning of linguistic capability. Our primary
      concern is how these capabilities can scaffold each other's development in a
      continuous feedback cycle as their interactions yield increasingly sophisticated
      competencies in the agent's capacity to interact with others and manipulate its
      world. Experimental results are summarized in relation to milestones in human
      linguistic and cognitive development and show that the mutual scaffolding of
      social learning, individual learning, and linguistic capabilities creates the
      context, conditions, and requisites for learning in each domain. Challenges and
      insights identified as a result of this research program are discussed with
      regard to possible and actual contributions to cognitive science and language
      ontogeny. In conclusion, directions for future work are suggested that continue
      to develop this approach toward an integrated framework for understanding these
      mutually scaffolding processes as a basis for language development in humans and
      robots. 

PMID- 24934295
TI  - Effects of replacement of factor VIII amino acids Asp519 and Glu665 with Val on
      plasma survival and efficacy in vivo.
AB  - Proteolytic cleavage of factor VIII (FVIII) to activated FVIIIa is required for
      participation in the coagulation cascade. The A2 domain is no longer covalently
      bound in the resulting activated heterotrimer and is highly unstable. Aspartic
      acid (D) 519 and glutamic acid (E) 665 at the A1-A2 and A2-A3 domain interfaces
      were identified as acidic residues in local hydrophobic pockets. Replacement with
      hydrophobic valine (V; D519V/E665V) improved the stability and activity of the
      mutant FVIII over the wild-type (WT) protein in several in vitro assays. In the
      current study, we examined the impact of mutations on secondary and tertiary
      structure as well as in vivo stability, pharmacokinetics (PK), efficacy, and
      immunogenicity in a murine model of Hemophilia A (HA). Biophysical
      characterization was performed with far-UV circular dichroism (CD) and
      fluorescence emission studies. PK and efficacy of FVIII was studied following
      i.v. bolus doses of 4, 10 and 40 IU/kg with chromogenic and tail clip assays.
      Immunogenicity was measured with the Bethesda assay and ELISA after a series of
      i.v. injections. Native secondary and tertiary structure was unaltered between
      variants. PK profiles were similar at higher doses, but at 4 IU/kg plasma
      survival of D519V/E665V was improved. Hemostasis at low concentrations was
      improved for the mutant. Immune response was similar between variants. Overall,
      these results demonstrate that stabilizing mutations in the A2 domain of FVIII
      can improve HA therapy in vivo.

PMID- 24934297
TI  - Light obscuration measurements of highly viscous solutions: sample pressurization
      overcomes underestimation of subvisible particle counts.
AB  - Light obscuration (LO) is the current standard technique for subvisible particle
      analysis in the quality control of parenterally administered drugs, including
      therapeutic proteins. Some of those, however, exhibit high viscosities due to
      high protein concentrations, which can lead to false results by LO measurements.
      In this study, we show that elevated sample viscosities, from about 9 cP, lead to
      an underestimation of subvisible particle concentrations, which is easily
      overlooked when considering reported data alone. We evaluated a solution to this
      problem, which is the application of sample pressurization during analysis. The
      results show that this is an elegant way to restore the reliability of LO
      analysis of highly viscous products without the necessity of additional sample
      preparation. 

PMID- 24934299
TI  - Evolution of electrocardiographic abnormalities in association with neuromuscular
      disorders and survival in left ventricular hypertrabeculation/noncompaction.
AB  - BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is
      frequently associated with neuromuscular disorders (NMDs) and
      electrocardiographic (ECG) abnormalities. The prognostic relevance of newly
      developed ECG abnormalities in LVHT and its dependency on NMD is largely unknown.
      Aim of the following retrospective cohort study in LVHT patients was thus to
      assess the development of new ECG abnormalities and its dependency on NMD and
      survival. METHODS: Included were patients in whom (a) LVHT was diagnosed between
      1995 and 2011, (b) baseline ECG recordings (bECG), and (c) follow-up ECG
      recordings (fECG) were available. Survival status was assessed in June 2013.
      RESULTS: Included were 105 patients (mean age 55 years, 36 females, 67 with NMD).
      The interval between bECG and fECG was 3.6 years. ECG abnormalities increased in
      46%, were unchanged in 44% and decreased in 11%. Increase was associated with age
      (59 years vs 49 years, P = 0.0169), exertional dyspnea (79% vs 53%, P = 0.013),
      heart failure (81% vs 47%, P = 0.0149), a left ventricular end-diastolic diameter
      >57 mm (76% vs 43%, P = 0.004) and a left ventricular fractional shortening <25%
      (68% vs 42%, P = 0.0429). New ECG abnormalities were ST-T wave abnormalities (n =
      35), left anterior hemiblock (n = 6) and Q waves (n = 6). During 71 months, 40
      patients died. Multivariate analysis identified age, male gender, "constant" (in
      bECG as well as fECG) atrial fibrillation, disappearance of atrial fibrillation,
      development as well as disappearance of low voltage ECG, increase of QRS width,
      constant QRS width >120 ms and constant tall QRS complexes as predictors for
      mortality. CONCLUSIONS: LVHT-patients develop frequently new ECG abnormalities of
      prognostic relevance.

PMID- 24934296
TI  - An electrically tight in vitro blood-brain barrier model displays net brain-to
      blood efflux of substrates for the ABC transporters, P-gp, Bcrp and Mrp-1.
AB  - Efflux transporters of the ATP-binding cassette superfamily including breast
      cancer resistance protein (Bcrp/Abcg2), P-glycoprotein (P-gp/Abcb1) and multidrug
      resistance-associated proteins (Mrp's/Abcc's) are expressed in the blood-brain
      barrier (BBB). The aim of this study was to investigate if a bovine
      endothelial/rat astrocyte in vitro BBB co-culture model displayed polarized
      transport of known efflux transporter substrates. The co-culture model displayed
      low mannitol permeabilities of 0.95 +/- 0.1 . 10(-6) cm.s(-1) and high
      transendothelial electrical resistances of 1,177 +/- 101 Omega.cm(2).
      Bidirectional transport studies with (3)H-digoxin, (3)H-estrone-3-sulphate and
      (3)H-etoposide revealed polarized transport favouring the brain-to-blood
      direction for all substrates. Steady state efflux ratios of 2.5 +/- 0.2 for
      digoxin, 4.4 +/- 0.5 for estrone-3-sulphate and 2.4 +/- 0.1 for etoposide were
      observed. These were reduced to 1.1 +/- 0.08, 1.4 +/- 0.2 and 1.5 +/- 0.1, by
      addition of verapamil (digoxin), Ko143 (estrone-3-sulphate) or zosuquidar +
      reversan (etoposide), respectively. Brain-to-blood permeability of all substrates
      was investigated in the presence of the efflux transporter inhibitors verapamil,
      Ko143, zosuquidar, reversan and MK 571 alone or in combinations. Digoxin was
      mainly transported via P-gp, estrone-3-sulphate via Bcrp and Mrp's and etoposide
      via P-gp and Mrp's. The expression of P-gp, Bcrp and Mrp-1 was confirmed using
      immunocytochemistry. The findings indicate that P-gp, Bcrp and at least one
      isoform of Mrp are functionally expressed in our bovine/rat co-culture model and
      that the model is suitable for investigations of small molecule transport.

PMID- 24934301
TI  - ExpertEyes: open-source, high-definition eyetracking.
AB  - ExpertEyes is a low-cost, open-source package of hardware and software that is
      designed to provide portable high-definition eyetracking. The project involves
      several technological innovations, including portability, high-definition video
      recording, and multiplatform software support. It was designed for challenging
      recording environments, and all processing is done offline to allow for
      optimization of parameter estimation. The pupil and corneal reflection are
      estimated using a novel forward eye model that simultaneously fits both the pupil
      and the corneal reflection with full ellipses, addressing a common situation in
      which the corneal reflection sits at the edge of the pupil and therefore breaks
      the contour of the ellipse. The accuracy and precision of the system are
      comparable to or better than what is available in commercial eyetracking systems,
      with a typical accuracy of less than 0.4 degrees  and best accuracy below 0.3
      degrees , and with a typical precision (SD method) around 0.3 degrees  and best
      precision below 0.2 degrees . Part of the success of the system comes from a high
      resolution eye image. The high image quality results from uncasing common digital
      camcorders and recording directly to SD cards, which avoids the limitations of
      the analog NTSC format. The software is freely downloadable, and complete
      hardware plans are available, along with sources for custom parts. 

PMID- 24934300
TI  - Beneficial or neutral effect of breastfeeding on cognitive outcomes in children
      of mothers with epilepsy?

PMID- 24934303
TI  - Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses
      after transplantation.
AB  - Immunosuppression of patients after hematopoietic stem cell or kidney
      transplantation potentially leads to reactivation of JC and BK polyomaviruses. In
      hematopoietic stem cell transplantation, the reactivation rate of BKV can be up
      to 60%, resulting in severe complications of the urogenital tract, particularly
      hemorrhagic cystitis and renal dysfunction. After kidney transplantation, BKV
      reactivation can cause a loss of the graft. JCV can cause progressive multifocal
      leukoencephalopathy, a lethal disease. Adoptive transfer of donor-derived
      polyomavirus-specific T cells is an attractive and promising treatment that
      restores virus-specific cellular immunity. Pioneering work in the early 1990s on
      the reconstitution of cellular immunity against cytomegalovirus and recent
      development in the field of monitoring and isolation of antigen-specific T cells
      paved the way toward a personalized T-cell therapy. Multimer technology and
      magnetic beads are available to produce untouched T cells in a single-step, good
      manufacturing practice-compliant procedure. Another exciting aspect of T-cell
      therapy against polyomaviruses is the fact that both JCV and BKV can be targeted
      simultaneously because of their high sequence homology. Finally, "designer T
      cells" can be redirected to recognize polyomavirus antigens with high-affinity T
      cell receptors. This review summarizes the state-of-the art technologies and
      gives an outlook of future developments in the field. 

PMID- 24934302
TI  - PPAR-alpha and PPAR-beta expression changes in the hippocampus of rats undergoing
      global cerebral ischemia/reperfusion due to PPAR-gamma status.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs, including alpha,
      beta and gamma subtypes) and their agonists have a protective role in treatment
      of central nervous system (CNS) diseases. The present study was designed to
      investigate the expression changes of PPAR-alpha, -beta, -gamma and NF-kappa B in
      the hippocampus of rats with global cerebral ischemia/reperfusion injury (GCIRI)
      after treatment with agonists or antagonists of PPAR-gamma. METHODS: A rat GCIRI
      model was established by occlusion of bilateral common carotid arteries and
      cervical vena retransfusion. GW9662 (5 MUg), a selective PPAR- gamma antagonist,
      was intraventricularly injected at 0.5 h before GCIR; Rosiglitazone (0.8, 2.4 and
      7.2 mg/kg), a selective PPAR- gamma agonist, was injected intraperitoneally at 1
      h before GCIRI. The expression changes of PPAR-alpha, -beta and -gamma at mRNA
      and protein levels were detected by RT-PCR and western blotting. The changes of
      spatial learning and memory (SLM) functions were assessed by using a Morris water
      maze; the pathohistological changes of hippocampal neurons were evaluated by
      hematoxylin-eosin (HE) staining; the contents of IL-1, IL-6, IL-10 and TNF-alpha,
      and the NF- kappa B expression were measured by enzyme-linked immunosorbent assay
      (ELISA) and immunohistochemical staining. The superoxide dismutase (SOD) activity
      and malondialdehyde (MDA) content were also detected. RESULTS: The SLM function
      and hippocampal neurons were significantly impaired after the occurrence of
      GCIRI. The MDA, IL-1, IL-6, IL-10, TNF-alpha content and expression of PPARs
      increased significantly, but the SOD activity and NF-kappa B expression were
      weakened in the hippocampus. Rosiglitazone treatment significantly protected rats
      from SLM function impairment and neuron death, and resulted in higher expressions
      of SOD activity and NF-kappa B, but lower contents of MDA and inflammatory
      factors. After treatment with rosiglitazone or GW9662, no significant change in
      PPAR-alpha or -beta expression was detected. CONCLUSIONS: Rosiglitazone, a PPAR
      gamma agonist, plays a protective role in hippocampal neuron damage of GCIRI rats
      by inhibiting the oxidative stress response and inflammation. The activation or
      antagonism of PPAR-gamma did not affect the expression of PPAR-alpha or -beta,
      indicating that the three subtypes of PPARs act in independent pathways in the
      CNS.

PMID- 24934304
TI  - Distinct phenotype and therapeutic potential of gingival fibroblasts.
AB  - Gingiva of the oral mucosa provides a practical source to isolate fibroblasts for
      therapeutic purposes because the tissue is easily accessible, tissue discards are
      common during routine clinical procedures and wound healing after biopsy is fast
      and results in complete wound regeneration with very little morbidity or
      scarring. In addition, gingival fibroblasts have unique traits, including neural
      crest origin, distinct gene expression and synthetic properties and potent
      immunomodulatory functions. These characteristics may provide advantages for
      certain therapeutic approaches over other more commonly used cells, including
      skin fibroblasts, both in intraoral and extra-oral sites. However, identity and
      phenotype of gingival fibroblasts, like other fibroblasts, are still not
      completely understood. Gingival fibroblasts are phenotypically heterogeneous, and
      these...fibroblast subpopulations may play different roles in tissue maintenance,
      regeneration and pathologies. The purpose of this review is to summarize what is
      currently known about gingival fibroblasts, their distinct potential for tissue
      regeneration and their potential therapeutic uses in the future. 

PMID- 24934305
TI  - Heterotopic bone formation derived from multipotent stromal cells is not
      inhibited in aged mice.
AB  - BACKGROUND AIMS: Decreased bone formation with age is believed to arise, at least
      in part, because of the influence of the senescent microenvironment. In this
      context, it is unclear whether multipotent stromal cell (MSC)-based therapies
      would be effective for the treatment of bone diseases. METHODS: With the use of a
      heterotopic bone formation model, we investigated whether MSC-derived
      osteogenesis is impaired in aged mice compared with young mice. RESULTS: We found
      that bone formation derived from MSCs is not reduced in aged mice. These results
      are supported by the unexpected finding that conditioned media collected from
      ionizing radiation-induced senescent MSCs can stimulate mineralization and delay
      osteoclastogenesis in vitro. CONCLUSIONS: Overall, our results suggest that
      impaired bone formation with age is mainly cell-autonomous and provide a
      rationale for the use of MSC-based therapies for the treatment of bone diseases
      in the elderly.

PMID- 24934306
TI  - Optimal condition of heparin-conjugated fibrin with bone morphogenetic protein-2
      for spinal fusion in a rabbit model.
AB  - BACKGROUND AIMS: Heparin-conjugated fibrin (HCF) is a carrier for long-term
      release of bone morphogenetic protein-2 (BMP-2) and has been shown to promote
      bone formation in animal models. We performed an experimental study to determine
      the optimal dose of BMP-2 with an HCF carrier that promotes bone formation
      comparable to that of autograft while minimizing complications in spinal fusion.
      METHODS: Twenty-four rabbits underwent posterolateral fusion of the L5-6 spinal
      segments. Different concentrations of HCF BMP-2 (1/10, 1/20, 1/30 or 1/40) were
      implanted in the spines of experimental rabbits, and autograft or INFUSE was
      implanted in the spines of control animals. Eight weeks after treatment, spinal
      fusion efficacy was evaluated by plain radiography, micro-computed tomography
      (micro-CT), mechanical testing and histomorphometry. RESULTS: Similar to
      autograft, the 1/40 HCF BMP-2 showed significant bone formation on micro-CT and
      histomorphometry with mechanical stability. However, the other HCF BMP-2
      concentrations did not show significant bone formation compared with autograft.
      Although conventional BMP-2 (INFUSE) led to higher bone formation and stability,
      it also led to excessive ectopic bone and fibrous tissue formation. CONCLUSIONS:
      This study suggests the optimal concentration of BMP-2 using HCF for spinal
      fusion, which may decrease the complications of high-dose conventional BMP-2.

PMID- 24934307
TI  - Strengthening implementation and utilization of nutrition interventions through
      research: a framework and research agenda.
AB  - Undernutrition among women and children contributes to almost half the global
      burden of child mortality in developing countries. The impact of nutrition on
      economic development has highlighted the need for evidence-based solutions and
      yielded substantial global momentum. However, it is now recognized that the
      impact of evidence-based interventions is limited by the lack of evidence on the
      best operational strategies for scaling up nutrition interventions. With the goal
      of encouraging greater engagement in implementation research in nutrition and
      generating evidence on implementation and utilization of nutrition interventions,
      this paper brings together a framework and a broad analysis of literature to
      frame and highlight the crucial importance of research on the delivery and
      utilization of nutrition interventions. The paper draws on the deliberations of a
      high-level working group, an e-consultation, a conference, and the published
      literature. It proposes a framework and areas of research that have been quite
      neglected, and yet are critical to better understanding through careful research
      to enable better translation of global and national political momentum for
      nutrition into public health impact. 

PMID- 24934308
TI  - Percutaneous treatment of left main coronary stenosis following bentall surgery.
AB  - A 65-year-old male underwent percutaneous coronary stenting of the left main
      trunk seven months after the Bentall procedure as a probable consequence of
      surgical glue.

PMID- 24934309
TI  - In reply.

PMID- 24934310
TI  - Cerebrospinal fluid pressure after epidural blood patching.

PMID- 24934311
TI  - Atypical headache following dural puncture in obstetrics.
AB  - BACKGROUND: In obstetrics, post-dural puncture headache is a well-recognised
      complication. Typical symptoms include fronto-temporal or occipital headache,
      worsening with ambulation and improving in the decubitus position. Occasionally,
      patients present with non-postural headache, although relatively little is known
      about this atypical presentation. The purpose of this study was to determine the
      incidence, associated signs and risk factors for this atypical manifestation of
      post-dural puncture headache. METHODS: We analysed a series of 27 064 parturients
      having a neuraxial procedure between January 2001 and December 2010. Using data
      from electronic anaesthesia patient records, medical charts and a postpartum
      quality audit, we identified all parturients with atypical post-dural puncture
      headache. We assessed the incidence and used uni- and multivariate analysis to
      identify associated risk factors. RESULTS: Amongst 142 parturients with post
      dural puncture headache, eight (5.6%, 95% CI 1.7-9.4%) had atypical non-postural
      headache. Associated symptoms were stiffness and pain in the cervical, thoracic
      or lumbar vertebral area, visual disturbances and vertigo. Significant risk
      factors for developing atypical signs were previous migraine, odds ratio 6.1 (95%
      CI 1.2-28.7), a more cephalad level of needle insertion, odds ratio 17.2 (95% CI
      1.4-210.1) and identification of dural puncture by aspiration of cerebrospinal
      fluid from the epidural catheter, odds ratio 5.5 (95% CI 1.2-24.4). Following
      multivariate analysis, recognition of dural puncture by aspiration of
      cerebrospinal fluid from the epidural catheter was the most significant predictor
      of non-orthostatic postdural puncture headache. CONCLUSION: Anaesthetists should
      be aware of this atypical clinical presentation, particularly if there is a past
      history of migraine, a more cephalad level of needle insertion or identification
      of dural puncture by aspiration of cerebrospinal fluid from the epidural
      catheter.

PMID- 24934312
TI  - Inter-ethnic differences in genetic polymorphisms of xenobiotic-metabolizing
      enzymes (CYP1A1, CYP2D6, NAT1 and NAT2) in healthy populations: correlation with
      the functional in silico prediction.
AB  - Several studies have shown that many polymorphisms of the xenobiotic-metabolizing
      enzymes (XME) affect either enzymatic functions or are associated with various
      aspects of human health. Owing to the presence of these single nucleotide
      variants (SNVs), differences in detoxification capacity have been observed
      between many ethnicities. The aim of this investigation was to study the
      prevalence of four polymorphisms in XME among various ethnic groups. Attention
      was focused on polymorphisms of CYP2D6 (rs1058172, G>A, p.Arg365His), CYP1A1
      (rs4646421, c.-26-728C>T), NAT1 (rs4921880, c.-85-1014T>A) and NAT2 (rs1208, A>G,
      p.Arg268Lys). These polymorphisms were analyzed in 261 healthy Tunisians
      individuals in comparison with different ethnic backgrounds from hapmap database.
      In addition, in silico functional prediction was also performed to determine the
      loss of function variants. Our results demonstrated that population's origins
      widely affect the genetic variability of XME enzymes and Tunisians show a
      characteristic pattern. In silico predictions showed a deleterious effect for
      p.Arg268Lys substitution on CYP2D6 function, findings confirmed its key role
      played in cancer susceptibility. These data show that detoxification genes
      structures depend on the studied population. This suggests that ethnic
      differences impact on disease risk or response to drugs and therefore should be
      taken into consideration in genetic association studies focusing on XME enzymes.
      Our results provide the first report on these SNV in Tunisian population and
      could be useful for further epidemiological investigations including targeted
      therapy.

PMID- 24934313
TI  - Matrilin-3 as a putative effector of C-type natriuretic peptide signaling during
      TGF-beta induced chondrogenic differentiation of mesenchymal stem cells.
AB  - C-type natriuretic peptide (CNP) signaling has been implicated as an important
      regulator of chondrogenic differentiation during endochondral bone development.
      This preliminary study further investigated the putative effectors and/or targets
      of CNP signaling in transforming growth factor (TGF)-beta induced in vitro
      chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously
      characterized human trabecular bone derived MSCs were induced either with only
      TGF-beta1 or with a combination of TGF-beta1 and CNP in micromass culture for 10
      or 20 days. Genome wide gene expression profile changes in between these two
      groups were analyzed on day-10 or day-20 of culture. Results revealed that there
      were only 7 genes, whose expression change was fourfolds or higher in TGF-beta1
      and CNP fed group in comparison to only TGF-beta1 fed group. The up-regulated
      genes included matrilin-3 (MATN3), engulfment and cell motility 1 (ELMO1), CD24,
      and DCN1, defective in cullin neddylation 1, domain containing 1 (DCUN1D1). The
      down-regulated genes, on the other hand, included LIM domain kinase 2 (LIMK2),
      Ewing sarcoma breakpoint region 1, and guanine nucleotide binding protein (G
      protein), gamma 12 (GNG12). The up-regulation of MATN3 was confirmed on the basis
      of RT-PCR. The known literature on both CNP signaling and MATN3 function in
      chondrogenesis match with each other and suggest MATN3 as a putative effector
      and/or target of CNP signaling during this process.

PMID- 24934314
TI  - Hepatobiliary cystadenocarcinoma without mesenchymal stroma in a female patient:
      a case report.
AB  - BACKGROUND: Hepatobiliary cystadenocarcinoma is a rare epithelial malignant
      neoplasm of the liver or extrahepatic bile ducts. Early diagnosis of
      hepatobiliary cystadenocarcinoma is difficult because of its asymptomatic
      features and rarity. Moreover, the molecular pathogenesis of hepatobiliary
      cystadenocarcinoma remains unclear. Herein, we described a case of hepatobiliary
      cystadenocarcinoma in female with chronic hepatitis B and repeated
      hepatolithiasis. CASE PRESENTATION: A 65-year-old woman with medical history of
      latent hepatitis B virus infection, repeated choledocholisthiasis, and
      cholecystitis was admitted due to a heterogeneous cystic mass (5.6 cm * 4 cm)
      shown on abdominal ultrasonography during regular physical checkup. The patient
      complained about irregular bowel movements with intermittent diarrhea for two
      months before presentation. Computed tomography (CT) disclosed a multiloculated
      cystic lesion in the left hepatic lobe with the presence of intraductal stones
      and dilatation of intrahepatic ducts. Histological results obtained from left
      lobectomy specimens showed hepatobiliary cystadenocarcinoma without accompanied
      mesenchymal stroma. CONCLUSION: Notably, hepatobiliary cystadenocarcinoma without
      mesenchymal stroma seldom occurs in women and is usually associated with poor
      prognosis. We present the rare findings in this patient and suggest that chronic
      inflammatory insults in the intrahepatic bile ducts might shed light on the
      cystadenocarcinogenesis.

PMID- 24934316
TI  - Spatial, ontogenetic and interspecific variability in stable isotope ratios of
      nitrogen and carbon of Merluccius capensis and Merluccius paradoxus off South
      Africa.
AB  - General linear models (GLMs) were used to determine the relative importance of
      interspecific, ontogenetic and spatial effects in explaining variability in
      stable isotope ratios of nitrogen (delta(15) N) and carbon (delta(13) C) of the
      co-occurring Cape hakes Merluccius capensis and Merluccius paradoxus off South
      Africa. Significant GLMs were derived for both isotopes, explaining 74 and 56% of
      observed variance in Merluccius spp. delta(15) N and delta(13) C, respectively.
      Spatial effects (west or south coast) contributed most towards explaining
      variability in the delta(15) N model, with Merluccius spp. off the west coast
      having higher (by c. 1.40/00) delta(15) N levels than Merluccius spp. off the
      south coast. Fish size and species were also significant in explaining
      variability in delta(15) N, with both species showing significant linear
      increases in delta(15) N with size and M. capensis having higher (by c. 0.70/00)
      delta(15) N values than M. paradoxus. Species and coast explained most and
      similar amounts of variability in the delta(13) C model, with M. capensis having
      higher (by c. 0.80/00) delta(13) C values than M. paradoxus, and values being
      lower (by c. 0.70/00) for fishes off the west coast compared with the south
      coast. These results not only corroborate the knowledge of Merluccius spp.
      feeding ecology gained from dietary studies, in particular the ontogenetic change
      in trophic level corresponding to a changing diet, but also that M. capensis
      feeds at a slightly higher trophic level than M. paradoxus. The spatial
      difference in Merluccius spp. delta(15) N appears due to a difference in isotopic
      baseline, and not as a result of Merluccius spp. feeding higher in the food web
      off the west than the south coast, and provides new evidence that corroborates
      previous observations of biogeographic differences in isotopic baselines around
      the South African coast. This study also provides quantitative data on the
      relative trophic level and trophic width of Cape hakes over a large size range
      that can be used in ecosystem models of the southern Benguela.

PMID- 24934315
TI  - Longitudinal assessment of physical activity in women undergoing Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: Patients undergoing bariatric surgery do not seem to increase
      objectively measured physical activity (PA) after surgery, despite substantial
      weight loss. The aims of the present study were (i) to objectively characterize 3
      months pre-surgery to 9 months postsurgery PA and sedentary behavior changes in
      women undergoing Roux-en-Y gastric bypass (RYGB) using tri-axial accelerometers
      and (ii) to examine associations between pre-surgery versus postsurgery PA and
      sedentary behavior with anthropometric measures taken in home environment.
      METHODS: Fifty-six women, with an average pre-surgery body mass index (BMI) of
      37.6 (SD 2.6) and of age 39.5 years (SD 5.7), were recruited at five Swedish
      hospitals. PA was measured for 1 week by the Actigraph GT3X+ accelerometer, and
      anthropometric measures were taken at home visits 3 months pre-surgery and 9
      months postsurgery, thus limiting seasonal effects. RESULTS: Average BMI loss, 9
      months postsurgery, was 11.7 (SD 2.7) BMI units. There were no significant pre-
      to postsurgery differences in PA or sedentary behavior. However, pre-surgery PA
      showed negative association with PA change and positive association with
      postsurgery PA. Adjustments for pre-surgery BMI had no impact on these
      associations. CONCLUSIONS: No significant differences were observed in
      objectively measured changes in PA or time spent sedentary from 3 months pre
      surgery to 9 months postsurgery among women undergoing RYGB. However, women with
      higher pre-surgery PA decreased their PA postsurgery while women with lower pre
      surgery PA increased their PA.

PMID- 24934317
TI  - The effect of K101 Nail Solution on Trichophyton rubrum and Candida albicans
      growth and ultrastructure.
AB  - K101 Nail Solution (trademarks Emtrix((r)), Nalox(TM), Naloc(TM)) is a
      combination of propylene glycol, urea and lactic acid in a topical formulation
      for the treatment of nails affected by onychomycosis. The aim of this study was
      to investigate the Minimal Cidal Concentration (MCC) of K101 Nail Solution
      against Trichophyton rubrum and Candida albicans as well as the effect of K101
      Nail Solution on the micromorphology of these fungi. The MCC of K101 Nail
      Solution against T. rubrum and C. albicans was 50% after 60-min exposure time. A
      MCC of 50% for K101 Nail Solution means that K101 Nail Solution diluted with e.g.
      water to 50% will totally kill the fungi tested. In the scanning electron
      microscope C. albicans cells, treated with 50% K101 Nail Solution, showed a
      shrunken surface. T. rubrum cells were severely damaged shown as collapse and
      degradation of the cells. In the transmission electron microscope most C.
      albicans cells, treated with 50% K101 Nail Solution exhibited destroyed
      organelles and many necrotic cells were found. The cell wall was clearly degraded
      and the contact between the cell wall and the inner membrane was punctured. In T.
      rubrum most cells were necrotic. Some cells were clearly collapsed and the
      content in the cytoplasm was degraded shown as small membrane vesicles and many
      big vacuoles. The cell wall was clearly degraded and the membrane was punctured.
      In conclusion, this in vitro study documents the efficacy of K101 Nail Solution
      against T. rubrum and C. albicans.

PMID- 24934319
TI  - Boy born with severe brain damage is awarded L12m.

PMID- 24934318
TI  - Association between low-frequency ultrasound and hip fractures -- comparison with
      DXA-based BMD.
AB  - BACKGROUND: New methods for diagnosing osteoporosis and evaluating fracture risk
      are being developed. We aim to study the association between low-frequency (LF)
      axial transmission ultrasound and hip fracture risk in a population-based sample
      of older women. METHODS: The study population consisted of 490 community-dwelling
      women (78-82 years). Ultrasound velocity (V(LF)) at mid-tibia was measured in
      2006 using a low-frequency scanning axial transmission device. Bone mineral
      density (BMD) at proximal femur measured using dual-energy x-ray absorptiometry
      (DXA) was used as the reference method. The fracture history of the participants
      was collected from December 1997 until the end of 2010. Lifestyle-related risk
      factors and mobility were assessed at 1997. RESULTS: During the total follow-up
      period (1997-2010), 130 women had one or more fractures, and 20 of them had a hip
      fracture. Low V(LF) (the lowest quartile) was associated with increased hip
      fracture risk when compared with V(LF) in the normal range (Odds ratio, OR = 3.3,
      95% confidence interval (CI) 1.3-8.4). However, V(LF) was not related to fracture
      risk when all bone sites were considered. Osteoporotic femoral neck BMD was
      associated with higher risk of a hip fracture (OR = 4.1, 95% CI 1.6-10.5) and
      higher risk of any fracture (OR = 2.4, 95% CI 1.6-3.8) compared to the non
      osteoporotic femoral neck BMD. Decreased VLF remained a significant risk factor
      for hip fracture when combined with lifestyle-related risk factors (OR = 3.3, 95%
      CI 1.2-9.0). CONCLUSION: Low V(LF) was associated with hip fracture risk in older
      women even when combined with lifestyle-related risk factors. Further development
      of the method is needed to improve the measurement precision and to confirm the
      results.

PMID- 24934320
TI  - Cost-benefit analysis of polysomnography versus Clinical Assessment Score-15 (CAS
      15) for treatment of pediatric sleep-disordered breathing.
AB  - OBJECTIVE: To determine the cost of medical care using the Clinical Assessment
      Score-15 (CAS-15) scale versus polysomnography (PSG) for children with sleep
      disordered breathing in terms of benefit. STUDY DESIGN: Cost-benefit analysis.
      SETTING: Hospital-based pediatric otolaryngology practice. SUBJECTS AND METHODS:
      Ninety-three patients from our original CAS-15 study were included. Four clinical
      measures were used and payment data were obtained. Cost-benefit analysis was
      performed for 2 clinical pathways. In pathway 1, all children had PSG; those with
      positive studies were referred for adenotonsillectomy. In pathway 2, children
      with CAS-15 >= 32 were referred for adenotonsillectomy regardless of PSG. Paired
      t test compared intrasubject mean total cost (pathway 1 vs pathway 2). Further
      analyses computed a change score for the clinical measures (follow-up minus
      baseline); these were divided by estimated treatment cost, producing 4 cost
      benefit ratios for each pathway. Paired t tests compared the mean of these ratios
      between the pathways. RESULTS: Of 65 PSG+ (15 CAS-), 54 underwent surgery; of 28
      PSG- (17 CAS-), 7 underwent surgery. Model estimated costs demonstrate a mean
      cost benefit of $US1172 (SE = $214) for pathway 2 versus pathway 1 (P < .001).
      CAS-15 is also cost-beneficial versus PSG in 3 of 4 clinical measures (Child
      Behavior Checklist total problem T score, P = .008, mean OSA-18 survey score, P <
      .001, apnea hypopnea index, P < .001). CONCLUSIONS: We present evidence that a
      CAS-15-based treatment decision criterion is superior to PSG in terms of monetary
      cost and in benefit per unit cost for 3 of 4 clinical measures evaluated.

PMID- 24934321
TI  - 2,4-D adsorption to biochars: effect of preparation conditions on equilibrium
      adsorption capacity and comparison with commercial activated carbon literature
      data.
AB  - Batch isotherm experiments were conducted with chars to study adsorption of the
      herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Chars generated from corncobs,
      bamboo and wood chips in a laboratory pyrolyzer at 400-700  degrees C were
      compared with traditional kiln charcoals collected from villages in S/SE Asia and
      with activated carbons (ACs). 2,4-D uptake by laboratory chars obtained from
      bamboo and wood chips after 14 h of pyrolysis at 700  degrees C, from wood chips
      after 96 h of pyrolysis at 600  degrees C, and one of the field-collected chars
      (basudha) was comparable to ACs. H:C and O:C ratios declined with pyrolysis
      temperature and duration while surface area increased to >500 m(2)/g. Increasing
      pyrolysis intensity by increasing temperature and/or duration of heating was
      found to positively influence adsorption capacity yield (mg(2,4-D/g(feedstock)))
      over the range of conditions studied. Economic analysis showed that high
      temperature chars can be a cost-effective alternative to ACs for water treatment
      applications.

PMID- 24934322
TI  - Nitrate reduction by mixed iron(II-III) hydroxycarbonate green rust in the
      presence of phosphate anions: the key parameters influencing the ammonium
      selectivity.
AB  - The reduction of nitrate anions by a mixed Fe(II)-Fe(III) carbonated green rust
      (GR) in aqueous medium is studied as a function of the initial pH and the initial
      concentrations of iron, phosphate and nitrate. The influence of these parameters
      on the fraction of nitrate removed and the production of ammonium is investigated
      by the help of statistical experimental designs. The goal is to determine
      experimental conditions that maximize the fraction of NO3(-) removed and
      concomitantly minimize the production of NH4(+). Increasing the phosphate
      concentration relatively to the initial Fe(II) concentration inhibits the
      reduction of nitrate probably due to a surface saturation of the lateral sites of
      the GR crystals. The kinetics of the reaction is greatly enhanced by increasing
      the initial pH at 10.5, however it leads to a global increase of the NH4(+)
      production. A partial saturation of the surface sites by phosphate leads to a
      global decrease of selectivity of the reaction towards ammonium. The evolution of
      the ratio of the NH4(+) concentration to the Fe(II) concentration confirms that
      the NO3(-) species are only partially transformed into ammonium. Interestingly at
      an initial pH of 7.5, the selectivity of the reaction towards NH4(+) is often
      lower than ~30%. The reduction of nitrate by carbonated GR differs from the
      behavior of other GRs incorporating Cl(-), F(-) and SO4(2-) anions that fully
      transform nitrate into ammonium. Finally, if GR is intended to be used during a
      passive water denitrification process, complementary dephosphatation and ammonium
      treatments should be considered. 

PMID- 24934323
TI  - Activating persulfate by Fe0 coupling with weak magnetic field: performance and
      mechanism.
AB  - Weak magnetic field (WMF) and Fe(0) were proposed to activate PS synergistically
      (WMF-Fe(0)/PS) to degrade dyes and aromatic contaminants. The removal rates of
      orange G (OG) by WMF-Fe(0)/PS generally decreased with increasing initial pH (3.0
      10.0) and increased with increasing Fe(0) (0.5-3.0 mM) or PS dosages (0.5-3.0
      mM). Compared to its counterpart without WMF, the WMF-Fe(0)/PS process could
      induce a 5.4-28.2 fold enhancement in the removal rate of OG under different
      conditions. Moreover, the application of WMF significantly enhanced the
      decolorization rate and the mineralization of OG. The degradation rates of
      caffeine, 4-nitrophenol, benzotriazole and diuron by Fe(0)/PS were improved by
      2.1-11.1 fold due to the superimposed WMF. Compared to many other sulfate radical
      based advanced oxidation technologies under similar reaction conditions, WMF
      Fe(0)/PS technology could degrade selected organic contaminants with much greater
      rates. Sulfate radical was identified to be the primary radical species
      responsible for the OG degradation at pH 7.0 in WMF-Fe(0)/PS process. This study
      unraveled that the presence of WMF accelerated the corrosion rate of Fe(0) and
      thus promoted the release of Fe(2+), which induced the increased production of
      sulfate radicals from PS and promoted the degradation of organic contaminants.
      Employing WMF to enhance oxidation capacity of Fe(0)/PS is a novel, efficient,
      promising and environmental-friendly method since it does not need extra energy
      and costly reagents.

PMID- 24934324
TI  - Acoustic and aerodynamic measures of the voice during pregnancy.
AB  - BACKGROUND: Known influences of sex hormones on the voice would suggest pregnancy
      hormones could have an effect, yet studies using acoustic measures have not
      indicated changes. Additionally, no examination of the voice before the third
      trimester has been reported. Effect of pregnancy on the voice is relatively
      unexplored yet could be quite relevant to female speakers and singers.
      OBJECTIVES/HYPOTHESIS: It is possible that spectral and aerodynamic measures
      would be more sensitive to tissue-level changes caused by pregnancy hormones.
      DESIGN/METHODS: In this first longitudinal study of a 32-year-old woman's
      pregnancy, weekly voice samples were analyzed for acoustic (fundamental
      frequency, perturbation ratios of shimmer and jitter, Harmonic-to-Noise Ratio,
      spectral measures, and maximum phonation time) and aerodynamic (average airflow,
      peak flow, AC/DC ratio, open quotient, and speed quotient) parameters. RESULTS:
      All measures appeared generally stable during weeks 11-39 of pregnancy compared
      with 21 weeks postpartum. Slight decrease in minimum airflow and open speed
      quotient may reflect suspected vocal fold tissue changes. CONCLUSIONS: It is
      recommended that future studies monitor and test correlations among hormone
      levels, visual analyses of vocal fold mucosa, aerodynamic function, and glottal
      efficiency.

PMID- 24934325
TI  - Ischemia-reperfusion rat model of acute pancreatitis: protein carbonyl as a
      putative early biomarker of pancreatic injury.
AB  - Acute pancreatitis (AP) is an inflammatory disorder that can affect adjacent
      and/or remote organs. Some evidence indicates that the production of reactive
      oxygen species is able to induce AP. Protein carbonyl (PC) derivatives, which can
      also be generated through oxidative cleavage mechanisms, have been implicated in
      several diseases, but there is little or no information on this biomarker in AP.
      We investigated the association between some inflammatory mediators and PC, with
      the severity of ischemia-reperfusion AP. Wistar rats (n = 56) were randomly
      assigned in the following groups : control; sham, 15- or 180-min clamping of
      splenic artery, with 24 or 72 h of follow-up. The relationships between serum
      level of PC and thiobarbituric acid reactive species (TBARS) to myeloperoxidase
      (MPO) activity in tissue homogenates and to cytokines in culture supernatants of
      pancreatic samples were analyzed. MPO activity was related to the histology
      scores and increased in all clamping groups. Tumor necrosis factor-alpha (TNF
      alpha), interleukin 1 beta (IL-1beta), and interleukin-6 were higher in the 180
      min groups. Significant correlations were found between MPO activity and the
      concentrations of TNF-alpha and IL-1beta. PC levels increased in the 15-min to 24
      h group. TBARS levels were not altered substantially. MPO activity and TNF-alpha
      and IL-1beta concentrations in pancreatic tissue are correlated with AP severity.
      Serum levels of PC appear to begin to rise early in the course of the ischemia
      reperfusion AP and are no longer detected at later stages in the absence of
      severe pancreatitis. These data suggest that PC can be an efficient tool for the
      diagnosis of early stages of AP. 

PMID- 24934326
TI  - Association of circulating levels of RANTES and -403G/A promoter polymorphism to
      acute heart failure after STEMI and to cardiogenic shock.
AB  - Chemokines, including RANTES, play a crucial role in the processes of
      inflammation during cardiovascular disorders, including myocardial infarction,
      disease progression and complications. This study aimed to evaluate the role of
      RANTES -403G/A polymorphism and levels in circulation in processes of development
      and progression of myocardial infarction and cardiogenic shock. A total of 609
      patients with ST-segment elevation myocardial infarction, 43 patients with
      cardiogenic shock and 130 control subjects were enrolled in the study. RANTES 
      403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In
      the present study, we associated RANTES -403G/A promoter polymorphism with acute
      heart failure in patients with myocardial infarction (p = 0.006) and ejection
      fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating
      RANTES levels among controls and STEMI subjects, and a relation of serum levels
      with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We
      found a significant difference when comparing cardiogenic shock patients and
      controls (p < 0.001), with the most significant difference between cardiogenic
      shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing
      tendency of serum RANTES levels with the severity of myocardial infarction and
      progression, with the lowest levels in patients with cardiogenic shock (cutoff
      level >=80.4 ng/ml). Our results suggest the role of RANTES as a potential
      biomarker of cardiogenic shock and acute heart failure in the hospital phase
      after myocardial infarction. 

PMID- 24934327
TI  - Expression of AKR1C3 and CNN3 as markers for detection of lymph node metastases
      in colorectal cancer.
AB  - The aim of the study was to identify a set of discriminating genes that could be
      used for the prediction of Lymph node (LN) metastasis in human colorectal cancer
      (CRC), and for this, we compared the whole genome profiles of two CRC cell lines
      (the primary cell line SW480 and its LN metastatic variant, SW620) and identified
      eight genes [S100 calcium-binding protein P; aldo-keto reductase family 1(AKR1),
      member B1 (aldose reductase; AKR1B1); AKR1, member C3 (AKR1C3); calponin 3,
      acidic; metastasis associated in colon cancer 1; hemoglobin, epsilon 1; trefoil
      factor 3; and FGGY carbohydrate kinase domain containing]. These genes were
      examined by quantitative RT-PCR in tissues and LNs in 14 CRC patients and 11
      control patients. The level of AKR1C3 mRNA expression was significantly different
      between the Dukes' stage A, B, and C groups and the control group (p < 0.05, p <
      0.001, and p < 0.001) and was also significantly different between Dukes' stage C
      and A or B groups (p < 0.05 and p < 0.001, respectively). The expression of CNN3
      was significantly different between the Dukes' stage C and B or control groups (p
      < 0.001 and p < 0.01, respectively). There were significant correlations between
      the expression levels of AKR1C3 and CNN3. AKR1C3 and CNN3 expressions are more
      accurate and suitable markers for the diagnosis of LN metastasis than the other
      six genes examined in this study. 

PMID- 24934328
TI  - Role of mandibular displacement and airway size in improving breathing after
      rapid maxillary expansion.
AB  - BACKGROUND: Oral breathing and maxillary deficiency are often associated with
      steep mandibular plane angle, and retrognathic mandible compared with the faces
      of healthy controls. Some studies suggested that after rapid maxillary expansion,
      improvement in nasal breathing and repositioning of mandible with transitory
      increasing of facial height and, in some cases, spontaneous forward repositioning
      might occur. The above-mentioned mandibular effects could contribute to enlarge
      oropharynx volume with repositioning of tongue and soft palate with an
      improvement of upper airway volume after treatment. The aim of this study was to
      investigate by cone beam computed tomography the role of oropharyngeal volume and
      mandibular position changes after rapid maxillary expansion in patients showing
      improved breathing pattern confirmed by polysomnography exam. METHODS: The final
      sample of this retrospective study comprised 14 Caucasian patients (mean age 7.6
      years) who undergone rapid maxillary expansion with Haas-type expander banded on
      second deciduous upper molars. Cone beam computed tomography scans and
      polysomnography exams were collected before placing the appliance (T0) and after
      12 months (T1). Mandibular landmarks localization and airway semiautomatic
      segmentation on cone beam computed tomography scans allowed airway volume
      computing and measurements. RESULTS: No significant differences were found
      between oropharyngeal airway changes and mandibular displacement after rapid
      maxillary expansion in growing patients. CONCLUSIONS: The suggested improvement
      in upper airway and breathing after rapid maxillary expansion should be further
      related to different compartments of airway such as rhinopharynx and nasal
      cavity.

PMID- 24934329
TI  - Meningeal hemangiopericytoma only diagnosed at the time of late bone metastasis.
AB  - Hemangiopericytoma is a rare neoplasm. Primary meningeal hemangiopericytomas
      account for 1 to 7% of all meningeal tumors. In the literature, meningeal
      hemangiopericytomas are mainly case reports, which confirm an aggressive behavior
      with a high rate of local recurrence and extracranial metastasis. Metastasis can
      be seen many years after initial surgical excision of the primary tumor, and the
      most common sites include the bone, liver and lung. We present a pathological
      study of four meningeal hemangiopericytomas with bone metastases. All patients
      are male with a mean age of 46.5 years. Metastases only involved bone. Three out
      of four lesions were initially misdiagnosed as meningiomas. Only one case was
      initially correctly diagnosed as meningeal hemangiopericytoma. All patients
      underwent surgery with complete resection. Only the patient immediately diagnosed
      with meningeal hemangiopericytoma received postoperative radiation therapy. Three
      patients had bone metastases without local recurrence including the one who
      received radiation therapy. One patient recurred locally after 7 years, and bone
      metastasis was found at the same time. Our cases confirm that meningeal
      hemangiopericytomas are a separate entity and have a high recurrence rate despite
      complete surgical resection, with extracranial metastases, mainly to bone, even
      after long intervals.

PMID- 24934330
TI  - Nonadiabatic reaction mechanisms of the O((3)P) with cyclopentene.
AB  - The reaction mechanism of the ground state oxygen atom O((3)P) with cyclopentene
      is investigated theoretically. The triplet and singlet potential energy surfaces
      are calculated at the CCSD(T)//MP2/6-311G(d,p) level and the minimum energy
      crossing points (MECPs) between the two surfaces are located by means of the
      Newton-Lagrange method, from which the complex nonadiabatic reaction pathways are
      revealed. Based on the theoretical results, the most probable reaction mechanism
      of O((3)P) with c-C5H8 is described, which agrees with the experimental results
      nicely, including the condensed phase experiment. At the same time, the newly
      revealed reaction mechanism clarifies the previous controversial product
      distribution, and predicts the possible existence of the new enol product,
      cyclopentenol. 

PMID- 24934331
TI  - Validation of a guideline-based decision support system for the diagnosis of
      primary headache disorders based on ICHD-3 beta.
AB  - BACKGROUND: China may have the largest population of headache sufferers and
      therefore the most serious burden of disease worldwide. However, the rate of
      diagnosis for headache disorders is extremely low, possibly due to the relative
      complexity of headache subtypes and diagnostic criteria. The use of computerized
      clinical decision support systems (CDSS) seems to be a better choice to solve
      this problem. METHODS: We developed a headache CDSS based on ICHD-3 beta and
      validated it in a prospective study that included 543 headache patients from the
      International Headache Center at the Chinese PLA General hospital, Beijing,
      China. RESULTS: We found that the CDSS correctly recognized 159/160 (99.4%) of
      migraine without aura, 36/36 (100%) of migraine with aura, 20/21 (95.2%) of
      chronic migraine, and 37/59 (62.7%) of probable migraine. This system also
      correctly identified 157/180 (87.2%) of patients with tension-type headache
      (TTH), of which infrequent episodic TTH was diagnosed in 12/13 (92.3%), frequent
      episodic TTH was diagnosed in 99/101 (98.0%), chronic TTH in 18/20 (90.0%), and
      probable TTH in 28/46 (60.9%). The correct diagnostic rates of cluster headache
      and new daily persistent headache (NDPH) were 90.0% and 100%, respectively. In
      addition, the system recognized 32/32 (100%) of patients with medication overuse
      headache. CONCLUSIONS: With high diagnostic accuracy for most of the primary and
      some types of secondary headaches, this system can be expected to help general
      practitioners at primary hospitals improve diagnostic accuracy and thereby reduce
      the burden of headache in China.

PMID- 24934332
TI  - Voluntary exercise improves performance of a discrimination task through effects
      on the striatal dopamine system.
AB  - We have previously demonstrated that voluntary exercise facilitates
      discrimination learning in a modified T-maze. There is evidence implicating the
      dorsolateral striatum (DLS) as the substrate for this task. The present
      experiments examined whether changes in DLS dopamine receptors might underlie the
      exercise-associated facilitation. Infusing a D1R antagonist into the DLS prior to
      discrimination learning facilitated the performance of nonexercising rats but not
      exercising rats. Infusing a D2R antagonist impaired the performance of exercising
      rats but not nonexercising rats. Exercise-associated facilitation of this task
      may rely on an exercise-induced decrease in D1R and increase in D2R activation in
      the DLS. 

PMID- 24934333
TI  - Young and old Pavlovian fear memories can be modified with extinction training
      during reconsolidation in humans.
AB  - Extinction training during reconsolidation has been shown to persistently
      diminish conditioned fear responses across species. We investigated in humans if
      older fear memories can benefit similarly. Using a Pavlovian fear conditioning
      paradigm we compared standard extinction and extinction after memory reactivation
      1 d or 7 d following acquisition. Participants who underwent extinction during
      reconsolidation showed no evidence of fear recovery, whereas fear responses
      returned in participants who underwent standard extinction. We observed this
      effect in young and old fear memories. Extending the beneficial use of
      reconsolidation to older fear memories in humans is promising for therapeutic
      applications. 

PMID- 24934334
TI  - Repetition strengthens target recognition but impairs similar lure
      discrimination: evidence for trace competition.
AB  - Most theories of memory assume that representations are strengthened with
      repetition. We recently proposed Competitive Trace Theory, building on the
      hippocampus' powerful capacity to orthogonalize inputs into distinct outputs. We
      hypothesized that repetition elicits a similar but nonidentical memory trace, and
      that contextual details of traces may compete for representation over time. We
      designed a task in which objects were incidentally encoded either one or three
      times. Supporting our theory, repetition improved target recognition, but
      impaired rejection of similar lures. This suggests that, in contrast to past
      beliefs, repetition may reduce the fidelity of memory representations. 

PMID- 24934335
TI  - Vancomycin-associated acute kidney injury in pediatric cardiac intensive care
      patients.
AB  - OBJECTIVE: Acute kidney injury (AKI) is a significant source of morbidity among
      critically ill pediatric patients, including those that have undergone cardiac
      surgery. Vancomycin may contribute to AKI in pediatric patients admitted to a
      cardiac intensive care unit. DESIGN AND SETTING: Patients admitted to the cardiac
      intensive care unit at Texas Children's Hospital and received vancomycin over a 4
      year period were included in a case-control study. Patients were excluded if they
      underwent renal replacement therapy during vancomycin therapy. Patient
      demographic and disease state variables, vancomycin therapy variables, and use of
      other nephrotoxic medications were collected. The overall incidence of AKI was
      calculated based on doubling of serum creatinine during or within 72 hours of
      vancomycin therapy (vancomycin-associated AKI [vAKI]). Patients who developed
      vAKI were matched with three patients who did not develop vAKI, and conditional
      logistic regression was used to determine independent risk factors for vAKI.
      RESULTS: A total of 418 patients met study criteria (males 57.8%) and infants (31
      days to 2 years) were the most populous age group (48.6%). Vancomycin-associated
      AKI occurred in 30 patients (7.2%), which resulted in a total of 120 patients (30
      cases; 90 controls). No significant differences were noted in vancomycin dosing
      between groups. Vancomycin-associated AKI patients were less likely to have
      undergone cardiac surgery (P < .05), more likely to have undergone extracorporeal
      membrane oxygenation (P < .05), and had greater exposure to nephrotoxic
      medications (P < .05). A conditional logistic regression model identified
      extracorporeal membrane oxygenation as associated with vAKI (odds ratio 14.4, 95%
      confidence interval 1.02-203, P = .048) and patients with prior cardiovascular
      surgery (odds ratio 0.10, 95% confidence interval 0.02-0.51, P < .01) or an
      elevated baseline serum creatinine (odds ratio 0.009, 95% confidence interval
      0.0002-0.29, P < .01) as less likely to develop vAKI. CONCLUSIONS: Vancomycin
      associated AKI occurs infrequently in the pediatric cardiac intensive care
      population and is strongly associated with patient critical illness.

PMID- 24934336
TI  - An update on the pharmacological strategies in the treatment of HIV-1-associated
      adipose redistribution syndromes.
AB  - INTRODUCTION: With the introduction of combination antiretroviral therapy (ART)
      for HIV infection in the mid-1990s, descriptions of morphological changes and
      metabolic disturbances in treated patients began to emerge. HIV-1/highly active
      ART-associated lipodystrophy syndrome (HALS) involves metabolic abnormalities and
      diverse forms of anomalous fat distribution. The current review focuses on the
      pathophysiological basis and the clinical evidence for the use of several medical
      strategies in the management of HALS. AREAS COVERED: We have covered the most
      relevant studies related to the pharmacological strategies in the treatment of
      HALS, with attention to the current and novel antiretroviral agents. EXPERT
      OPINION: The most commonly used strategies for HALS reversion have included
      modification of host-dependent factors, including those related to HIV-1
      infection and those associated with ART. Preventive and medical strategies have
      been associated with moderate success. The only intervention that offers an
      immediate aesthetical improvement for patients with HALS so far has been plastic
      surgery.

PMID- 24934337
TI  - Highly selective detection of trinitrophenol by luminescent functionalized
      reduced graphene oxide through FRET mechanism.
AB  - Among different nitro compounds, trinitrophenol (TNP) is the most common
      constituent to prepare powerful explosives all over the world. A few works on the
      detection of nitro explosives have already been reported in the past few years;
      however, selectivity is still in its infant stage. As all the nitroexplosives are
      highly electron deficient in nature, it is very difficult to separate one from a
      mixture of different nitro compounds by the usual photoinduced electron transfer
      (PET) mechanism. In the present work, we have used a bright luminescent, 2,6
      diamino pyridine functionalized graphene oxide (DAP-RGO) for selective detection
      of TNP in the presence of other nitro compounds. The major advantage of using
      this material over other reported materials is not only to achieve very high
      fluorescence quenching of ~96% but also superior selectivity >80% in the
      detection of TNP in aqueous medium via both fluorescence resonance energy
      transfer and PET mechanisms. Density functional theory calculations also suggest
      the occurrence of an effective proton transfer mechanism from TNP to DAP-RGO,
      resulting in this tremendous fluorescence quenching compared to other nitro
      compounds. We believe this graphene based composite will emerge a new class of
      materials that could be potentially useful for selective detection, even for
      trace amounts of nitro explosives in water. 

PMID- 24934338
TI  - Velocity distributions in confined flows of some complex fluids: sequence, sample
      and hardware issues.
AB  - The present work addresses the problem of using Pulsed Field Gradient (PFG)
      experiments to measure velocity probability density functions and/or
      distributions in restricted flows, without being subjected to the blurring due to
      diffusive molecular motions. It especially focuses on two important classes of
      complex yield-stress fluids, i.e. water based colloidal suspensions or polymeric
      gels, and concentrated emulsions. Taking into account the many constraints owing
      to fluid diffusive properties, flow rate, hardware characteristics and pore size,
      it is found that the existence of suitable and optimised sequence parameters can
      be discussed in a graphical way. To do so, it also shown that Murday and Cotts
      formula describing diffusion inside emulsion droplets can be efficiently
      approximated by means of a set of asymptotic expressions. Different tuning
      regimes are identified for both kind of fluids, highlighting the influence of
      each of the various constraints on measuring possibilities. A method is given to
      build quantitative diagrams indicating pore sizes and flow rates allowing pure
      velocity assessment for a given fluid and Nuclear Magnetic Resonance (NMR)
      hardware. Measurements are found to be mainly constrained by fluid self
      diffusivity and microstructure at low flow rates, and hardware characteristics at
      high flow rates. Although high gradient strengths can be made necessary to
      decrease achievable velocities and pore sizes in some specific cases, low
      gradient systems turn out suitable in many situations thanks to optimised
      sequence tuning. Due to their larger size, the latter also appear to offer the
      widest variety of workable experimental conditions. The use of these results is
      finally exemplified on the practical case of an emulsion flow in a model porous
      system. 

PMID- 24934339
TI  - Greater daily defined dose of antihypertensive medication increases the risk of
      falls in older people--a population-based study.
AB  - OBJECTIVES: To determine whether there is a relationship between daily defined
      dose (DDD) of antihypertensive drugs and the risk of falls. DESIGN: Prospective
      population-based cohort study. SETTING: Tasmanian Study of Cognition and Gait,
      Australia. PARTICIPANTS: Participants aged 60 to 86 randomly selected from the
      electoral roll. MEASUREMENTS: Antihypertensive dose was quantified by estimating
      DDD, allowing standardized comparison of dosage between drug classes. Falls were
      identified prospectively over 12 months. The relative risk (RR) of falls
      associated with DDD was estimated using log binomial regression adjusting for
      age, sex, body mass index, education, cardiovascular history, and other risk
      factors for falls. RESULTS: Participants (N=409) had a mean age of 72.0+/-6.9,
      and 56% were male. Mean baseline blood pressure was 142/80 mmHg, and 54% were
      taking antihypertensive medications. One hundred sixty-one participants (39%)
      fell over the 12 months. Those who fell were on a higher DDD of antihypertensives
      (1.51+/-2.16 than those who did not (1.03+/-1.42) (P=.007). Higher DDD was
      independently associated with greater fall risk (RR=1.07, 95% confidence interval
      (CI)=1.02-1.11; P=.004), with a 48% greater risk in those with a DDD of more than
      3 (RR=1.48, 95% CI=1.06-2.08; P=.02), particularly in those with a history of
      stroke (P for interaction .01). This effect remained even after excluding those
      not taking antihypertensives or stratifying according to presence of hypertension
      and medication use. CONCLUSION: Higher dose of antihypertensive medication is
      independently associated with falls in older people, particularly in those with a
      history of previous stroke, and with more than three standard units conferring
      the highest risk.

PMID- 24934340
TI  - Chemical constituents and antimicrobial properties of the essential oil and
      ethanol extract from the stem of Aglaia odorata Lour.
AB  - The stem-derived essential oil of Aglaia odorata Lour. was obtained by
      hydrodistillation using a Clevenger-type system. Gas chromatography-mass
      spectrometry analysis of the oil revealed the identification of 39 compounds,
      representing 76.4% of the oil; germacrene D (20.3%), alpha-humulene (17.1%),
      alpha-himachalene (12.7%) and beta-caryophyllene (10.2%) were the major
      components. Ar-turmerone (1) and eichlerialactone (2) were isolated from the stem
      oil and ethanolic stem extract of this plant species, respectively. Antimicrobial
      activities of the oil and ethanol extract were tested against both Gram-positive
      and Gram-negative bacterial strains including Bacillus cereus ATCC 11778,
      Staphylococcus aureus ATCC 25923, Acinetobacter baumannii ATCC 19606 and
      Escherichia coli ATCC 25922, as well as three rice fungal pathogens Bipolaris
      oryzae, Pyricularia oryzae and Rhizoctonia solani using broth microdilution
      method. The oil and 1 exhibited significant antifungal activity against the three
      rice pathogens tested, whereas 2 exhibited good antibacterial activity against
      both the Gram-positive pathogens tested. 

PMID- 24934341
TI  - Chelating agents for the sequestration of mercury(II) and monomethyl mercury(II).
AB  - Both mercury(II) and monomethyl mercury(II) poisonings are of great concern for
      several reasons. As it happens for other metals, chelation therapy is the most
      indicated treatment for poisoned patients. The efficacy of the therapy and the
      reduction of side-effects can be sensibly enhanced by an accurate knowledge of
      all the physiological mechanisms involved in metal uptake, transport within and
      between various tissues, and (possibly) clearance. All these aspects, however,
      are strictly dependent on the chemical speciation (i.e., the distribution of the
      chemical species of a component in a given system) of both the metal and the
      chelating agent in the systems where they are present. In this light, this review
      analyzes the state of the art of research performed in this field for mercury(II)
      and methylmercury(II). After a brief summary of their main sources, the
      physiological patterns for the treatment of mercury poisoning have also been
      considered. The binding ability of various chelating agents toward mercury has
      been then analyzed by modeling the behavior of the main classes of ligands
      present in biological fluids and/or frequently used in chelation therapy. Their
      sequestering ability has been successively evaluated by means of a semiempirical
      parameter already proposed for its objective quantification, and the main
      characteristics of an efficient chelating agent have been evaluated on this
      basis. 

PMID- 24934342
TI  - Targeting the phosphatidylinositol 3-kinase/AKT pathway for the treatment of
      multiple myeloma.
AB  - Multiple myeloma is the second most hematological malignancy, accounting for more
      than 10% of all blood cancers and 2% of annual cancer-related deaths due to lack
      of curable drugs. Novel and molecularly targeted anti-MM drugs are in urgent
      need. The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays a
      critical regulatory role in multiple myeloma pathophysiology, including survival,
      proliferation, migration, angiogenesis, as well as drug resistance, and has
      emerged as a key therapeutic target. Many potent inhibitors targeting this
      pathway have been developed and some have been moved for clinical evaluations for
      multiple myeloma. In this review, we highlighted the role of the PI3K/AKT pathway
      in the pathogenesis of multiple myeloma, and current advances in drug discovery
      for this class of inhibitors. Discovery strategies toward the PI3K/AKT inhibitors
      were also discussed. 

PMID- 24934343
TI  - Effect of DNA repair deficiencies on the cytotoxicity of drugs used in cancer
      therapy - a review.
AB  - Tumor cells often have defects in DNA repair pathways that make them vulnerable
      to specific DNA-damaging anticancer agents. The identification of DNA repair
      defects in tumor cells and the evaluation of their influence on the cytotoxicity
      of anticancer drugs are active areas of scientific investigation that may help
      rationalize and improve cancer chemotherapy. This article reviews the available
      data on the influence of defects in proteins involved in the major DNA repair
      pathways (i.e., homologous recombination, non-homologous end joining, base
      excision repair, nucleotide excision repair, mismatch repair, Fanconi anemia
      repair, translesion synthesis and direct reversal repair) on the cytotoxicity of
      the FDA-approved anticancer drugs. It is shown that specific deficiencies in
      these DNA repair pathways alter the cytotoxicity of 60 anticancer drugs,
      including classical DNA-targeting drugs (e.g., alkylating agents, cytotoxic
      antibiotics, DNA topoisomerase inhibitors and antimetabolites) and other drugs
      whose primary pharmacological target is not the DNA (e.g., antimitotic agents,
      hormonal and targeted therapies). This information may help predict response to
      anticancer drugs in patients with tumors having specific DNA repair defects.

PMID- 24934344
TI  - Statins as bioactive molecules to support bone regeneration.
AB  - Statins are currently used as an effective cholesterol-lowering medication
      through inhibition of the mevalonate pathway, but recent studies show their
      potential for bone repair. The bone anabolic effects of statins have been largely
      attributed to their ability to enhance BMP-2 expression in osteoblast cells. In
      vitro studies have demonstrated that statins can increase the expression of
      osteogenic and angiogenic markers such as alkaline phosphatase, vascular
      endothelial growth factor, and osteocalcin in cells. In vivo, statins have been
      shown to promote significant new bone growth when injected systemically or
      locally in combination with a scaffold. The potential anabolic effects of statins
      on bone make them attractive candidates to support bone regeneration. Since the
      molecular pathways by which statins induce osteoblast differentiation are still
      unclear, further investigations are required to elucidate the detailed cellular
      signaling mechanisms involved to determine the type of statin, optimal dose and
      mode of delivery to effectively utilize their anabolic effect. This also warrants
      the development of novel vehicles to locally deliver statins for the desired time
      periods to support optimal tissue regeneration in vivo. 

PMID- 24934345
TI  - GABA system as a target for new drugs.
AB  - 4-Aminobutyric acid is an inhibitory neurotransmitter involved in the control of
      neuronal activity in the mammalian central nervous system. There is considerable
      direct and indirect evidence that impaired activity of GABAmediated inhibitory
      synapses may be an important causative factor in experimental and clinical
      seizure disorders. This review is focused on the recent development of compounds
      which can influence GABA neurotransmission by affecting the GABA receptors, the
      plasma-membrane GABA transporters (GATs) and catabolic enzyme GABA-transaminase
      (GABAT). These compounds have been primarily investigated in relation to
      epilepsy, but it has also been found that a decrease in GABA neurotransmission
      appears to be involved in the aetiology of several neurological disorders such as
      insomnia, spasticity, neuropathic pain, anxiety and other mental disorders. 

PMID- 24934346
TI  - DNA binding mode of transition metal complexes, a relationship to tumor cell
      toxicity.
AB  - Transition metal-based compounds constitute a distinct class of chemotherapeutics
      extensively used in the clinic as antitumor and antiviral agents. However, drug
      resistance and side effects of established antitumor metallodrugs such as
      cisplatin [cis-diamminedichloroplatinum(II)] and its analogues, carboplatin and
      oxaliplatin, have limited their clinical utility. These limitations have prompted
      a search for more effective and less toxic metal-based antitumor agents. The
      unique properties of metal ions, such as redox transfer/electron shuttling, and
      versatile coordination geometries arising from various oxidation states, result
      in metal ions and complexes that have potential medicinal applications that could
      be complementary to organic compounds and which are widely sought in drug
      discovery efforts. This review summarizes the results that show that transition
      metal complexes exhibit antitumor effects that differ from cisplatin or its
      analogues. 

PMID- 24934347
TI  - Novel in situ activity assays for the quantitative molecular analysis of
      neurodegenerative processes in the retina.
AB  - The mechanisms of neuronal cell death are still only poorly understood, which has
      hindered the advancement of therapies for many currently untreatable
      neurodegenerative diseases. This calls for the development of new methods which
      reveal critical molecular mechanisms of the celldeath machinery with both high
      sensitivity and cellular resolution. Using animal models for hereditary
      neurodegeneration in the retina, we have developed or adapted different
      biochemical assays to determine the enzymatic activities of calpain, poly-ADP
      ribose-polymerase (PARP), and histone deacetylase (HDAC) directly and in situ.
      Additionally, the enzymatic activity of cGMP-dependent protein kinase (PKG) was
      assessed indirectly using in situ immunohistological techniques to detect PKG
      activity-dependent products. Combining these assays with in situ cell death
      markers revealed close temporospatial correlations, suggesting causal connections
      between the PKG, HDAC, PARP and calpain activities and neuronal cell death. Using
      different pharmacological and genetic manipulations, causality could indeed be
      demonstrated. Surprisingly, the often dramatic rises in metabolic activities
      didnot match by corresponding increases in expression, highlighting the
      importance of analyses of protein activities at the cellular level. The above
      mentioned studies identified a number of metabolic processes previously unknownto
      be involved in inherited retinal degeneration. Comparing different animal retinal
      degeneration models uncovered striking similarities in enzymatic activities,
      suggesting a generality of the destructive pathways. Taken together, these
      findings provided a number of novel targets for neuroprotection and as such
      opened up new perspectives for the therapy of hereditary neurodegeneration in the
      retina and possibly other parts of the central nervous system. 

PMID- 24934348
TI  - Boronic acid-based enzyme inhibitors: a review of recent progress.
AB  - Since Bortezomib was approved by US FDA as the first drug to treat multiple
      myeloma, various boronic acid compounds have been developed as enzyme inhibitors.
      This paper reviewed the progress of boronic acid-based inhibitors against enzymes
      including proteasome, serine protease, HDACs and other enzymes in the past
      decade. 

PMID- 24934349
TI  - Mitochondria-targeted antioxidants as a therapeutic strategy for protecting
      endothelium in cardiovascular diseases.
AB  - Endothelial dysfunction involving dysfunctional mitochondria precedes the
      development of cardiovascular diseases. This impairment results from an increase
      in reactive oxygen species, which leads to oxidative stress and a reduced
      bioavailability of nitric oxide. It has been demonstrated that oxidative stress
      and alterations in glucose and lipid homeostasis (e.g. hyperinsulinemia,
      hyperglycemia, insulin resistance and dyslipidemia) are linked to mitochondrial
      impairment and that all of them contribute to endothelial dysfunction. Anti
      hyperlipidemic drugs such as statins, anti-hypertensive drugs and angiotensin
      receptor antagonists have been shown to exert protection through anti-oxidative
      stress mechanisms. Other substances with antioxidant properties, such as
      vitamins, are also capable of abolishing the oxidative stress associated with
      cardiometabolic diseases. However, the results obtained with general antioxidants
      in clinical trials are contradictory, perhaps due to the unspecific nature of the
      targets selected. This study correlates endothelial dysfunction and mitochondrial
      dysfunction and examines current research for the selective targeting of specific
      molecules (such as .NO donors and antioxidants) to mitochondria with the aim of
      protecting the endothelium against oxidative stress in cardiovascular diseases. 

PMID- 24934350
TI  - Salvianolic acid B inhibits atherogenesis of vascular cells through induction of
      Nrf2-dependent heme oxygenase-1.
AB  - AIMS: Salvianolic acid B (Sal B), one of the most active components of Danshen
      extracts, has beneficial roles in the prevention and treatment of cardiovascular
      diseases. However, the precise mechanism by which Sal B exerts its effects on
      vascular cells is unclear. We aimed to elucidate the effects of Sal B on vascular
      cells and the underlying mechanisms. METHODS AND RESULTS: Treatment of vascular
      smooth muscle cells with Sal B effectively inhibited platelet-derived growth
      factor (PDGF)-induced cell proliferation and migration, and markedly increased
      heme oxygenase-1 (HO-1) expression. These changes were accompanied by antioxidant
      effects, including decreases in the generation of reactive oxygen species and the
      NADP/NADPH ratio. In human umbilical vein endothelial cells, Sal B also strongly
      induced HO-1 and effectively inhibited tumor necrosis factor-alpha-induced NF
      kappaB activation. Knockdown of HO-1 expression by siRNA abolished the effects of
      Sal B in vascular cells and prevented the inhibition of proliferation, migration,
      and inflammation in HO-1-deficient cells. In ex vivo culture of arterial rings
      isolated from nuclear factor-E2-related factor 2 (Nrf2)-knockout mice, Sal B
      neither induce HO-1 expression and nor inhibit PDGF-induced neointimal
      hyperplasia in arteries, suggesting that Nrf2 plays a crucial role in the
      induction of HO-1 expression. CONCLUSIONS: We conclude that Sal B exerts
      antiatherogenic effects by inhibiting the proliferation, migration, and
      inflammation of vascular cells through induction of HO-1 via Nrf2 activation.

PMID- 24934351
TI  - Oxidative stress, redox signaling and cancer chemoresistance: putting together
      the pieces of the puzzle.
AB  - Chemotherapy continues to be the main treatment option for cancer. Although
      systemic chemotherapy can efficiently eradicate cancer cells, a significant
      proportion of patients carry tumors that present a chemoresistant phenotype,
      resulting in disease progression, cancer relapse, and reduced survival. It has
      also become clear that the effect of most chemotherapeutic drugs is associated
      with their capacity to generate reactive species (RS) that bind to specific
      structures within the cancer cell and promote cell death. Due to repeated
      exposure to chemotherapeutic agents, the redox homeostasis of cancer cells is
      continuously disturbed, which can result in changes to the cell's ability to cope
      with excessive RS levels through the production of protective molecules. It is
      thought that the imbalance resulting from this process-- oxidative stress--is
      toxic to cancer cells. Paradoxically, the metabolites produced during oxidative
      stress can favor the survival of some cancer subpopulations, which present
      specific gene signatures that confer a chemoresistant phenotype on these clones.
      Despite the huge amount of information generated by currently available
      technologies, we cannot predict whether this resistance will arise during
      chemotherapy and we still do not fully understand the mechanism by which it
      arises. In this review, we discuss the main findings regarding the role of
      oxidative stress signaling in cancer chemotherapy and the key redox molecules and
      pathways that lead to the development of chemoresistance.

PMID- 24934352
TI  - Novel Nor-Homo- and Spiro-Oxetan- Steroids Target the Human Androgen Receptor and
      Act as Antiandrogens.
AB  - The prostate adenocarcinoma is the cancer with the highest incidence for men in
      Western countries. Targeting the androgen receptor (AR) by antagonists is used as
      hormone therapy for prostate cancer (PCa), however, eventually therapy resistance
      occurs in most patients. In most of these cancer the AR signaling is active and
      thus AR remains an important drug target. Since many years we are characterizing
      novel chemical structural platforms to provide a broader possibility for
      compounds that bind to and act as AR antagonists. Here, we describe the chemical
      synthesis of a battery of novel steroidal derivatives as nor-homo-, spiro-oxolan-
      and spiro-oxetan- steroids. They modulate the transcriptional activity of the
      human AR. As AR antagonists, the spiro-oxetan- steroid derivatives seem to be the
      most potent steroid derivatives. They inhibit the transcriptional activity of
      both wild-type AR as well as the AR mutant T877A. In line with this, these
      compounds bind to the human AR and inhibit the proliferation of the human
      androgen-dependent growing PCa cell line LNCaP. Interestingly, the castration
      resistant AR expressing human PC3-AR cells are also growth inhibited. On
      mechanistic level, fluorescence resonance energy transfer (FRET) assays with
      living cells indicate that the androgen-induced N/C terminal interaction of the
      AR is inhibited by the investigated compounds. Using fluorescence recovery after
      photobleaching (FRAP) assays in living cells suggest a higher mobility of the AR
      in the cell nuclei in the presence of spiro-oxetan- steroidal antagonists.
      Together, these findings suggest that spiro-oxetan- steroids are very useful as a
      chemical platform for novel AR antagonists.

PMID- 24934353
TI  - Fetal programming of the human brain: is there a link with insurgence of
      neurodegenerative disorders in adulthood?
AB  - In recent years, evidence is growing on the role played by gestational factors in
      shaping brain development and on the influence of intrauterine experiences on
      later development of neurodegenerative diseases including Parkinson's (PD) and
      Alzheimer's disease (AD). The nine months of intrauterine development and the
      first three years of postnatal life are appearing to be extremely critical for
      making connections among neurons and among neuronal and glial cells that will
      shape a lifetime of experience. Here, the multiple epigenetic factors acting
      during gestation - including maternal diet, malnutrition, stress, hypertension,
      maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal
      infection, intrauterine growth restriction, drugs administered to the mother or
      to the baby - are reported, and their ability to modulate brain development,
      resulting in interindividual variability in the total neuronal and glial burden
      at birth is discussed. Data from recent literature suggest that prevention of
      neurodegeneration should be identified as the one method to halt the diffusion of
      neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD
      and successfully applied to AD and other neurodegenerative human pathologies,
      should focus our attention on a peculiar period of our life: the intrauterine and
      perinatal periods. The first hit to our nervous system occurs early in life,
      determining a PD or AD imprinting to our brain that will condition our resistance
      or, alternatively, our susceptibility to develop a neurodegenerative disease
      later in life. In conclusion, how early life events contribute to late-life
      development of adult neurodegenerative diseases, including PD and AD, is emerging
      as a new fascinating research focus. This assumption implies that research on
      prevention of neurodegenerative diseases should center on events taking place
      early in life, during gestation and in the perinatal periods, thus presenting a
      new challenge to perinatologists: the prevention of neurodegenerative human
      diseases. 

PMID- 24934354
TI  - Effects of iron and copper overload on the human liver: an ultrastructural study.
AB  - Iron and copper ions play important roles in many physiological functions of our
      body, even though the exact mechanisms regulating their absorption, distribution
      and excretion are not fully understood. Metal-related human pathology may be
      observed in two different clinical settings: deficiency or overload. The overload
      in liver cells of both trace elements leads to multiple cellular lesions. Here we
      report the main pathological changes observed at transmission electron microscopy
      in the liver of subjects affected by Beta-thalassemia and by Wilson's disease.
      The hepatic iron overload in beta-thalassemia patients is associated with
      haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes.
      Haemosiderin granules are grouped inside voluminous lysosomes, also called
      siderosomes. Other ultrastructural changes are fat droplets, proliferation of the
      smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and
      infiltration of sinusoids by polymorphonucleates is also detected in beta
      thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease
      patients are characterized by severe mitochondrial changes, associated with an
      increased number of perossisomes, cytoplasmic lipid droplets and the presence of
      lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles
      surrounded by electron-dense lysosomes. In patients affected by Wilson's disease,
      nuclei are frequently involved, with disorganization of the nucleoplasm and with
      glycogen inclusions. On the contrary, no significant changes are detected in
      Kupffer cells. Our data show that iron and copper, even though are both
      transition metals, are responsible of different pathological changes at
      ultrastructural level. In particular, copper overload is associated with
      mitochondrial damage, whereas iron overload only rarely may cause severe
      mitochondrial changes. These differences underlay the need for further studies in
      which biochemical analyses should be associated with ultrastructural data, in
      order to better understand the molecular ways associated with iron- and copper
      related pathology at subcellular level. 

PMID- 24934357
TI  - Copper chelators: chemical properties and bio-medical applications.
AB  - Copper is present in different concentrations and chemical forms throughout the
      earth crust, surface and deep water and even, in trace amounts, in the atmosphere
      itself. Copper is one of the first metals used by humans, the first artifacts
      dating back 10,000 years ago. Currently, the world production of refined copper
      exceeds 16,000 tons/year. Copper is a micro-element essential to life,
      principally for its red-ox properties that make it a necessary cofactor for many
      enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal
      species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as
      carriers of oxygen instead of hemoglobin. However, these red-ox properties also
      make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive
      oxygen species, when copper is present in excess in the body or in tissues. The
      treatment of choice in cases of copper overloading or intoxication is the
      chelation therapy. Different molecules are already in clinical use as chelators
      or under study or clinical trial. It is worth noting that chelation therapy has
      also been suggested to treat some neurodegenerative diseases or cardiovascular
      disorders. In this review, after a brief description of the homeostasis and some
      cases of dyshomeostasis of copper, the main (used or potential) chelators are
      described; their properties in solution, even in relation to the presence of
      metal or ligand competitors, under physiological conditions, are discussed. The
      legislation of the most important Western countries, regarding both the use of
      chelating agents and the limits of copper in foods, drugs and cosmetics, is also
      outlined.

PMID- 24934358
TI  - Cell to cell spreading of misfolded proteins as a therapeutic target in motor
      neuron disease.
AB  - Despite a number of genetic mutations and molecular mechanisms are recognized to
      participate in amyotrophic lateral sclerosis (ALS), such a devastating
      neurological disorder still lacks a substantial cure. The present manuscript
      rather than a general overview of potential therapeutic approaches focuses on
      novel research findings detailing novel molecular mechanisms which appear to be
      promising for developing future ALS therapeutics. A special emphasis is given to
      the abnormal autophagy status and to those autophagy substrates which aggregate
      in the form of misfolded proteins. In fact, as reviewed in the first part of the
      manuscript, altered autophagy pathway is present in most genetic mutations
      responsible for familial ALS. These mutations impair clearance of autophagy
      substrates, which determines accumulation of giant altered mitochondria and
      misfolded proteins. Therefore, a considerable piece of the review is dedicated to
      unconventional processing of misfolded proteins leading to unconventional protein
      secretions which may underlie a prionoid cellto- cell spreading of ALS
      neuropathology. The intimate mechanisms regulating these steps are analyzed in
      order to comprehend which potential therapeutic targets might be considered in
      future studies. At the same time, negative findings concerning recent trials are
      explained in light of novel disease mechanisms. In the final part of the review
      the replacement therapy with focal stem cells implantation is discussed in
      relationship with toxic mechanisms operating in the intercellular space of the
      spinal cord and motor-related areas.

PMID- 24934355
TI  - Potential therapeutic drugs and methods for the treatment of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder caused by
      damage of motoneurons leading to paralysis state and long term disability.
      Riluzole is currently the only FDA-approved drug for the treatment of ALS. The
      proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress,
      mitochondrial dysfunction, protein aggregation, SOD1 accumulations, and neuronal
      death. In this review, we discuss potential biomarkers for the identification of
      patients with ALS. We further emphasize potential therapy involving the uses of
      neurotrophic factors such as IGFI, GDNF, VEGF, ADNF-9, colivelin and angiogenin
      in the treatment of ALS. Moreover, we described several existing drugs such as
      talampanel, ceftriaxone, pramipexole, dexpramipexole and arimoclomol potential
      compounds for the treatment of ALS. Interestingly, the uses of stem cell therapy
      and immunotherapy are promising for the treatment of ALS.

PMID- 24934359
TI  - Biomarkers and future targets for development in amyotrophic lateral sclerosis.
AB  - Although the pathophysiological mechanisms underlying the development of
      amyotrophic lateral sclerosis (ALS) remain to be fully elucidated, there have
      been significant advances in the understanding of ALS pathogenesis, with evidence
      emerging of a complex interaction between genetic factors and dysfunction of
      vital molecular pathways. Glutamate- mediated excitoxicity is an important
      pathophysiological pathway in ALS, and was identified as an important therapeutic
      biomarker leading to development of the only pharmacologically based disease
      modifying treatment currently available for ALS. More recently, a putative role
      of voltage-gated persistent Na(+) channels in ALS pathogenesis has been suggested
      and underscored by neuroprotective effects of Na(+) channel blocking agents in
      animal models. In addition, advances in ALS genetics have lead to identification
      of novel pathophysiological processes that could potentially serve as therapeutic
      targets in ALS. Genetic therapies, including antisense oligonucleotide approaches
      have been shown to exert neuroprotective effects in animal models of ALS, and
      Phase I human trial have been completed demonstrating the feasibility of such a
      therapeutic approach. The present review summarises the advances in ALS
      pathogenesis, emphasising the importance of these processes as potential targets
      for drug development in ALS.

PMID- 24934360
TI  - Let's prioritize the right care for the right patients with hypertension.

PMID- 24934361
TI  - Expression of Ki-67, Bax and p73 in patients with hilar cholangiocarcinoma.
AB  - BACKGROUND: Hilar cholangiocarcinoma (HCC) is defined as a cholangiocarcinoma
      located in the bifurcation of the right and left bile duct, constituting 40%-60%
      of all reported cholangiocarcinoma and 58%-75% of the extrahepatic
      cholangiocarcinoma. In this study, we aim to investigate the expression of Ki-67,
      Bax and p73 in the patients with HCC, and identify their potential roles in the
      prognosis of HCC. OBJECTIVE: Thirty five HCC patients (male: 25, female: 10) with
      an average age of 62.8 years were diagnosed with HCC according to the
      pathological tests. A total of 20 cadavers with normal hilar bile ducts were used
      as control. METHODS: The expression of Ki-67, Bax, and p73 was determined using
      immunohistochemical analysis. RESULTS: The pathological test indicated that Ki-67
      expression increased with the stage of the disease, and the infiltration of the
      cancer cells. Statistical difference was noted in the expression of Bax LI
      between the patients with HCC and normal control (32.4 +/- 17.6 vs 11.2 +/- 7.9,
      P< 0.01). Statistical difference was observed between the patients with or
      without lymphatic metastasis, and those of various differentiation stages (P <
      0.05). Among the 35 patients with HCC, expression of p73 was observed in 11
      patients (31.43%). Compared with normal control, remarkable increase of p73
      expression was noted in the HCC patients (P < 0.01). Additionally, no statistical
      difference was noted in the expression of p73 in the patients with various
      disease stages, and those with or without metastasis (P> 0.05). CONCLUSIONS: Ki
      67, Bax, and p73 could be used as biomarkers for the prognosis of HCC.

PMID- 24934362
TI  - Serum p53 antibody in breast cancer.
AB  - BACKGROUND: The significance of the measurement of anti-p53 antibodies in serum
      remains undisclosed. The aim of this study was to assess anti-p53 antibodies in
      the serum of patients with breast cancer, and correlate these results with
      various clinicopathologic parameters. METHODS: We analyzed serum anti-p53
      antibody levels in 124 patients with breast cancers and 7 patients with benign
      disease between April 2012 and March 2013, as well as levels of serum
      carcinoembryonic antigen (CEA) and cancer antigen (CA) 15-3. RESULTS: Twenty-two
      of 124 patients with breast cancer had an increased concentration of anti-p53
      antibodies. By distribution of clinical stage, in stage 0-II the positive ratio
      of anti-p53 antibodies was significantly higher than that of CEA (p=0.03) and
      CA15-3 (p=0.01). There was a significant correlation between anti-p53 antibodies
      and family history (p=0.03). Triple-negative cancer also showed a significant
      correlation with anti-p53 antibodies (p=0.007). In patients with multiple and/or
      bilateral breast cancer, the level of anti-p53 was significantly higher than in
      unilateral breast cancer (62.5% vs 14.7%, p=0.004). CONCLUSION: Measurement of
      anti-p53 antibodies is useful for the prevention of oversight in the evaluation
      of multiple and/or bilateral breast cancer.

PMID- 24934363
TI  - Serum biomarkers for assessing histology and outcomes in patients with metastatic
      lung cancer.
AB  - BACKGROUND: Serum biomarkers are not in routine clinical use for diagnosis,
      prognosis, or treatment selection in lung cancer. OBJECTIVE: We examined serum
      protein biomarkers from patients with metastatic lung cancer to determine whether
      they correlate with progression-free survival (PFS), overall survival (OS), or
      histologic subtype. METHODS: Serum samples were collected prior to chemotherapy
      from 153 patients with metastatic lung cancer treated at Memorial Sloan-Kettering
      Cancer Center. Serum biomarkers were selected for ELISA testing based on their
      availability in a CLIA-certified clinical laboratory: ProGRP, SCC-Ag, NSE, CYFRA
      21-1, TIMP1, and HE4. Pretreatment biomarker levels were correlated with outcome
      using proportional hazards analysis and tumor histology using logistic regression
      analysis. RESULTS: Univariate analysis indicated that only higher levels of CYFRA
      21-1 were significantly associated with worsened PFS (HR 1.3, 95% CI 1.1--1.5, p<
      0.01) and OS (HR 1.4, 95% CI 1.2-1.7, p< 0.001). Multivariate analysis of NSE,
      CYFRA 21-1, and TIMP1 indicated that CYFRA 21-1 remained independently associated
      with lower OS (HR 1.3, 95% CI 1.1-1.6, p< 0.01). Univariate analysis indicated
      that ProGRP (OR 3.3, 95% CI 1.7-6.5, p< 0.001) and NSE (OR 4.8, 95% CI 2.6-8.8,
      p< 0.0001) had the highest probabilities of differentiating SCLC from NSCLC.
      Multivariate analysis of these two markers demonstrated that they predicted SCLC
      histology with 94% accuracy. Univariate analysis showed that only SCCL-Ag
      distinguished squamous cell histology from adenocarcinoma (OR 4.4, 95% CI 1.7
      11.5, p< 0.01). CONCLUSIONS: Serum CYFRA 21-1 may be useful in predicting patient
      survival, and serum ProGRP, NSE 21-1, and SCCL-Ag may be helpful in
      distinguishing between lung cancer sub-types.

PMID- 24934364
TI  - Molecular detection and prognostic value of epithelial markers mRNA expression in
      peripheral blood of advanced non-small cell lung cancer patients.
AB  - BACKGROUND: Few studies, have evaluated the prognostic impact of the
      quantification of mRNA expression levels in advanced non-small cell lung cancer
      (NSCLC). OBJECTIVE: The aim of this work was to quantify mRNA expression levels
      in peripheral blood through three epithelial markers in patients with stages IIIB
      and IV in NSCLC. METHODS: Seventy advanced NSCLC patients and ten healthy
      controls were included. All patients received platinum-based chemotherapy in
      first line treatment. Peripheral blood was obtained of each participant and mRNA
      expression levels present in circulating cells were quantified by molecular
      techniques (RT-PCR) using three epithelial markers: cytokeratin (CK)-18, CK-19
      and Carcinoembryonic-Antigen (CEA). The expression levels were quantified from a
      standard curve using the cDNA obtained from A549 cells. Registered in
      ClinicalTrials.gov (NCT01052818). RESULTS: We found a significant statistical
      correlation between levels of CK-18, CK-19 and CEA mRNA. mRNA expression levels
      were lower in patients who present three or less metastasis; higher CEA mRNA
      expression was associated a worse progression-free survival to platinum-based
      chemotherapy and overall survival. CONCLUSION: RNA expression of CEA by RT-PCR is
      useful as a prognostic marker in advanced NSCLC.

PMID- 24934365
TI  - Associations between hsa-miR-603 polymorphism, lifestyle-related factors and
      colorectal cancer risk.
AB  - BACKGROUND: Accumulated studies have suggested that single nucleotide
      polymorphisms (SNPs) in microRNAs are associated with risk of colorectal cancer
      (CRC). OBJECTIVE: We tested our hypothesis that rs11014002 in hsa-miR-603 may be
      associated with CRC risk with a crosstalk of life-related factors. METHODS: We
      conducted a case-control study which included 102 CRC patients and 204 matched
      cancer-free controls in Xiaoshan County. RESULTS: We observed that subjects with
      rs11014002 CT/TT genotype had an increased susceptibility for CRC (CT vs. CC:
      odds ratio (OR)=2.352, 95% confidence interval (CI): 1.142-4.840, P=0.020; CT+TT
      vs. CC: OR=2.031, 95% CI: 1.063-3.883, P=0.032). After stratification by
      lifestyle-related factors, similar results were found among nonsmokers (CT vs.
      CC: OR=2.753, 95% CI: 1.085-6.983, P=0.033; CT+TT vs. CC: OR=2.971, 95% CI: 1.188
      7.435, P=0.020) and non-alcohol drinkers (CT+TT vs. CC: OR=3.279, 95% CI: 1.071
      10.033, P=0.037). CONCLUSIONS: Our data suggest that hsa-miR-603 may be involved
      in colorectal tumorigenesis, and the genetic polymorphism in hsa-miR-603 is
      associated with CRC susceptibility.

PMID- 24934366
TI  - A novel inflammatory regulator TIPE2 inhibits TLR4-mediated development of colon
      cancer via caspase-8.
AB  - AIMS: TIPE2 is a novel inflammation regulator, and the role of TIPE2 in colitis
      induced colon cancer is not clear. The aim of this study was to test whether
      TIPE2 inhibits TLR4 pathway in colon cancer patients and to explore potential
      mechanism of TIPE2 in colon cancer by caspase-8. METHODS: Expression of TIPE2 and
      TLR4 in human colon cancer tissues and cell line HT-29 was detected by
      immunohistochemistry or real-time PCR. TIPE2 mRNA was suppressed by siRNA
      transfection and the transfection efficiency was proved by fluorescence
      microscopy and real-time PCR. TLR4 pathway was activated by treating the cells
      with 1 MUg/ml LPS for 4 h. Caspase-8 activities were tested by colorimetric assay
      in four HT-29 cell groups. RESULTS: TIPE2 was expressed in the cytoplasm of colon
      cancer tissues and HT-29 cells. TIPE2 expression was more pronounced in colon
      cancer tissues compared to normal controls and it was related with lymph node
      metastasis and Dukes stage of colon cancer. TIPE2 expression was positively
      correlated with that of TLR4 in colon cancer (r=0.7354). TIPE2 expression was
      knocked down successfully by siRNA transfection. Caspase-8 activity was elevated
      both in TIPE2 knockdown cells and in TLR4 activated cells compared to wild-type
      cells (P< 0.05). And the caspase-8 activity was further increased in TIPE2
      knockdown cells after TLR4 was activated (P < 0.05). CONCLUSION: TIPE2 can
      inhibit caspase-8 activity in colon cancer cells. TIPE2 can regulate TLR4
      inflammatory effect and inhibit further amplification of cascade reaction via
      caspase-8, which provides one new therapeutic target for clinical treatment
      schedule.

PMID- 24934367
TI  - High expression levels of CXCL12 and CXCR4 predict recurrence of adamanti
      nomatous craniopharyngiomas in children.
AB  - BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign but
      maldevelopmental tumor with a high recurrence rate. OBJECTIVE: Theaim of this
      study was to investigate the dysregulated biological molecules that play
      important roles in the recurrence of ACP. METHODS: We first performed microarray
      analysis on tumor samples from two pediatric patients with recurrent ACP and from
      two pediatric ACP patients without recurrence after a one-year follow-up. The
      expression of CXCL12 and CXCR4 in 45 specimens of pediatric ACP was further
      evaluated by immunohistochemistry. These results were correlated with the
      clinicopathological parameters and survival of the patients. RESULTS: Four
      downregulated genes (APC, ITGA, MCAM, and TIMP4) and 16 upregulated genes (CST7,
      CTSK, CTSL1, CXCL12, CXCR4, FN1, FXYD5, ITGB3, MMP2, MMP3, MMP7, MMP9, NR4A3,
      PLAUR, TIMP2, and VEGFA) were found in the recurrent patients. CXCL12 and CXCR4
      were highly expressed in 13 patients (28.9%) and 14 patients (31.1%),
      respectively. High levels of CXCL12 and CXCR4 expression were significantly
      associated with a poor recurrence-free survival and were the prognostic factors
      for ACP recurrence in pediatric patients. CONCLUSIONS: High levels of CXCL12 and
      CXCR4 expression were associated with ACP recurrence. The role of CXCL12 and
      CXCR4 in the development of brain tumors requires further research.

PMID- 24934368
TI  - Quantification of fibrin degradation products in glioma and meningioma patients.
AB  - BACKGROUND: DR-70 is an immunoassay for fibrin and FDP in plasma and it has been
      shown useful in detection of over 14 different cancers. This study investigated
      the validity of the DR-70 test in gliomas as well as meningiomas. METHODS: 77
      brain tumor patients as well as 40 healthy individuals were prospectively
      included in the study and investigated using DR-70 kit. The glioma cohort of 33
      patients consisted of 1, 11, 6 and 15 WHO grade 1, 2, 3 and 4 gliomas,
      respectively. The meningioma cohort of 44 patients contained 38, 5 and 1 WHO
      grade 1, 2 and 3 tumors. RESULTS: Test results were significantly higher than
      control values for both gliomas and meningiomas. The most balanced sensitivity
      and specificity values were obtained at cut-off level of 0.5 MUg/ml FDP for both
      gliomas and meningiomas. Above this cutoff level the relative-risk for having a
      glioma was 5.1 times higher compared to controls with sensitivity and specificity
      of 76% and 85%, respectively. The relative-risk for meningioma was 5.8 with a
      sensitivity and specificity of 87% and 85%, respectively. CONCLUSION: FDP
      testing, which is a nonspecific cancer screening tool, is sensitive to the two
      most common primary brain malignancies, gliomas and meningiomas.

PMID- 24934369
TI  - Adverse cardiovascular events predict survival benefit in non-small lung cancer
      patients treated with bevacizumab.
AB  - BACKGROUND: Bevacizumab is a monoclonal antibody against vascular endothelial
      growth factor (VEGF) that provides a survival benefit to patients with non-small
      cell lung cancer (NSCLC). However, the treatment is sometimes accompanied by life
      threatening bleeding events, and studies have not yet identified factors that can
      predict outcomes for NSCLC patients receiving bevacizumab. METHODS: To identify
      prognostic factors for patients with NSCLC who are undergoing bevacizumab
      therapy, this study retrospectively investigated 34 consecutive patients with
      NSCLC treated with bevacizumab-containing chemotherapy. RESULTS: Adverse
      cardiovascular events, including hypertension and bleeding events, during
      bevacizumab therapy were observed in 18 patients (53%). Kaplan-Meier survival
      analyses and log-rank tests revealed that median overall survival was
      significantly better in patients who experienced adverse cardiovascular events
      than those who did not (442 versus 304 days; P=0.012). In the multivariate Cox
      proportional hazard model, the onset of adverse cardiovascular events was
      independently associated with a better overall survival. CONCLUSIONS: The onset
      of adverse cardiovascular events during bevacizumab therapy may be a favorable
      prognostic factor for patients with NSCLC. The results of this retrospective
      study warrant further large-scale prospective trials.

PMID- 24934370
TI  - Epidermal growth factor receptor could play a prognostic role to predict the
      outcome of nasopharyngeal carcinoma: A meta-analysis.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) has been reported to play a
      prognostic role in nasopharyngeal carcinoma (NPC). Nevertheless, the effect of
      EGFR predicting clinical outcomes is still controversial. METHODS: Potentially
      eligible studies were retrieved using PubMed. Basic clinical characteristics of
      patients and statistical data were collected. Survival data can be got directly
      or could be calculated if it was available in other resources. Then, we used a
      meta-analysis model to review the correlation between over-expression of EGFR and
      survival outcome in NPC patients. RESULTS: 15 eligible studies and 1225 patients
      were yielded in our meta-analysis. The HRs with 95% confidence intervals (CIs)
      for OS and DFS/RFS/PFS were 2.11 [1.23, 3.60] and 2.17 [1.41, 3.35],
      respectively. Histological differentiation stage, race, different cut-off values
      and the percentage of TNM stage were divided for subgroup analysis. CONCLUSION:
      EGFR could be a fine prognostic factor of NPC, which might be proven by further
      multicenter clinical trials.

PMID- 24934371
TI  - Caveolin-1 as a biomarker to predict therapeutic effect of low-frequency
      ultrasound combined with SonoVue on prostate cancer in nude mice model.
AB  - BACKGROUND: Caveolin-1 is a major structural component of cell membrane
      invaginations. Over-expression of caveolin-1 is closely related to the
      tumorigenesis and progression of prostate cancer. Recently, contrast microbubbles
      in combination with ultrasound are being investigated for their therapeutic
      applications in tumor cells. However, the response of caveolin-1 after low
      frequency ultrasound and SonoVue treatment in animal model is unclear. OBJECTIVE:
      The goal of this study was to evaluate the effect of 80 kHz ultrasound and/or
      SonoVue on caveolin-1 expression and secretion in DU145 prostate tumors in nude
      mice. METHODS: Six-week-old BALB/c male nude mice were subcutaneously injected
      with DU145 cells in the right flank to establish a prostate cancer model, which
      were randomly divided into four groups (n=8 each): control group (sham-ultrasound
      exposure), SonoVue group, 80 kHz ultrasound group, 80 kHz ultrasound combined
      with SonoVue group. Tumor volumes and wet weights were measured, and the tumor
      volume curve was obtained as well. The mice were euthanized 21 days after
      treatment. Specimens of the tumor tissues were assessed the expression of
      caveolin-1 by immunohistochemistry and Western blot. The serum concentrations of
      caveolin-1 were detected by ELISA. RESULTS: Treatment with ultrasound alone
      produced tumor volumes and weights reduction compared with control and SonoVue
      group. Combined ultrasound and SonoVue treatment produced greater tumor
      regression than either treatment alone (p < 0.05). Serum caveolin-1
      concentrations were lower in the combination of ultrasound and SonoVue group than
      they were in control group (p =0.005), and had some certain correlation with
      tumor growth (wet weight) (r =0.507), although the difference was not
      statistically significant (p=0.199). Ultrasound alone treatment only slightly
      reduced the caveolin-1 concentrations in comparison with the control, and the
      difference was not statistically significant (p=0.125). The ultrasound-treated
      mice showed significant reduction in expression levels of caveolin-1 protein,
      compared with the control (p < 0.05). Levels of caveolin-1 were further reduced
      when combined with ultrasound and SonoVue as compared to the control (p < 0.01).
      CONCLUSIONS: Our results suggest that 80 kHz ultrasound have antitumor effect and
      the effect could be further strengthened by the combination of SonoVue. Down
      regulating the expression of caveolin-1 is likely a potential biomarker of
      response to ultrasound and SonoVue treatment in prostate cancer mouse model.

PMID- 24934372
TI  - Association of cytotoxic T lymphocyte antigen-4 +49A/G polymorphism and cancer
      risk: An updated meta-analysis.
AB  - BACKGROUND: Associations between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49A/G
      polymorphism and cancer risk are inconclusive. We performed this meta-analysis to
      derive a more precise estimation of the relationship. METHODS: A comprehensive
      literature search was performed using electronic databases. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to assess the strength of
      association. RESULTS: A total of 16,358 cases and 19,737 controls from 46 studies
      were included. Overall, significant association between CTLA-4 +49A/G
      polymorphism and cancer risk was observed in all genetic models (G vs. A:
      OR=0.88, 95%CI=0.83-0.93, PH=0.000; GA vs. AA: OR=0.87, 95%CI=0.79-0.97,
      PH=0.000; GG vs. AA: OR=0.75, 95%CI= 0.65-0.86, PH=0.000; GG vs. GA+AA: OR=0.84,
      95%CI=0.79-0.91, PH=0.001; GG+GA vs. AA: OR=0.83, 95%CI=0.74-0.92, PH=0.000).
      Stratified analysis by cancer type revealed that the CTLA-4+49A/G polymorphism is
      associated with the decreased risk of cervical cancer, breast cancer, lung
      cancer, HCC. Further subgroup analysis by ethnicity indicated that there was a
      statistically decreased cancer risk in Asian population. CONCLUSION: This meta
      analysis suggests that CTLA-4+49A/G polymorphism is associated with cancer risk,
      especially in Asian population.

PMID- 24934374
TI  - Using nanoscale and mesoscale anisotropy to engineer the optical response of
      three-dimensional plasmonic metamaterials.
AB  - The a priori ability to design electromagnetic wave propagation is crucial for
      the development of novel metamaterials. Incorporating plasmonic building blocks
      is of particular interest due to their ability to confine visible light. Here we
      explore the use of anisotropy in nanoscale and mesoscale plasmonic array
      architectures to produce noble metal-based metamaterials with unusual optical
      properties. We find that the combination of nanoscale and mesoscale anisotropy
      leads to rich opportunities for metamaterials throughout the visible and near
      infrared. The low volume fraction (<5%) plasmonic metamaterials explored herein
      exhibit birefringence, a skin depth approaching that of pure metals for selected
      wavelengths, and directionally confined waves similar to those found in optical
      fibres. These data provide design principles with which the electromagnetic
      behaviour of plasmonic metamaterials can be tailored using high aspect ratio
      nanostructures that are accessible via a variety of synthesis and assembly
      methods. 

PMID- 24934373
TI  - Calcific myonecrosis following snake bite: a case report and review of the
      literature.
AB  - INTRODUCTION: Calcific myonecrosis is a rare condition in which muscle in a limb
      compartment undergoes necrosis and becomes peripherally calcified with central
      liquefaction. The patient usually presents with a slowly progressive enlarged
      mass that sometimes can be misdiagnosed as soft tissue sarcoma. Most of the
      reported cases showed that the disease occurs often after trauma or compartment
      syndrome. However, the case of calcific myonecrosis following snake bite is
      rarely reported. CASE PRESENTATION: A 66-year-old Thai woman presented with a
      gradually progressive enlarged mass over a period of 10 years in her left leg.
      She had a history of untreated compartment syndrome after she was bitten by a
      snake (Malayan pit viper) in her left leg when she was 14-years old. At
      presentation, a plain X-ray showed a large soft tissue mass at the anterior
      compartment of her left leg. A sheet-like mass with an enlarged central cavity
      combined with peripheral calcification and cortical erosion of her tibia were
      observed. A biopsy was performed and the result was negative for neoplastic
      cells. During a 5-year follow-up, the mass progressively enlarged and then became
      infected and finally broke through the skin. She was treated by excision of the
      mass and administration of antibiotics. The wound completed healed at 1 month
      postsurgery. There was no wound complication or disease recurrence at 1 year
      postoperation. CONCLUSIONS: The diagnosis of calcific myonecrosis was done by
      history taking and radiographic interpretation. In an asymptomatic patient the
      management should be observation and clinical follow-up. A biopsy should be
      avoided due to the high rate of postoperative infection. Treatment of choice in a
      symptomatic condition is mass excision.

PMID- 24934375
TI  - Effect of PGF2alpha and GnRH on the reproductive performance of postpartum dairy
      cows subjected to synchronization of ovulation and timed artificial insemination
      during the warm or cold periods of the year.
AB  - This study was designed to evaluate the reproductive performance of lactating
      dairy cows (Holstein Friesian) after the injection of PGF2alpha analogue on Day
      15 postpartum, and GnRH analogue on Day 23 after artificial insemination (AI)
      with Presynch (two injections of PGF2alpha, administered 14 days apart starting
      at 30-35 days postpartum) + Ovsynch-based (GnRH-7 days-PGF2alpha-2 days-GnRH-16
      20 hours-timed artificial insemination) treatments, during the warm and cold
      periods of the year. All the cows (n = 313) were assigned to one of the four
      groups including: M1 (n = 72) in which the cows were treated with PGF2alpha on
      Day 15 postpartum + Presynch-Ovsynch + GnRH on Day 23 post-AI; M2 (n = 41) in
      which the cows received PGF2alpha on Day 15 postpartum + Presynch-Ovsynch; M3 (n
      = 100) including the cows that got Presynch-Ovsynch; and control group (n = 100)
      including the cows that were not treated and were inseminated at natural estrus.
      Pregnancy diagnosis was performed 28 to 35 days post-insemination by means of
      ultrasound. The results showed that treatment with PGF2alpha on Day 15 postpartum
      significantly decreased the days to conception and the number of services per
      conception (P < 0.01) and it also improved the first service conception rate (P <
      0.1) only in cows that were treated with M2 protocol. Whereas, the days to first
      service was not influenced by the treatment of PGF2alpha on Day 15 postpartum (P
      > 0.05). In contrast, administration of GnRH on Day 23 post-AI increased the days
      to conception and the number of service per conception (P < 0.01) and tended to
      decrease the first service conception rate (P < 0.1) in cows that were treated
      with M1 compared with M2 protocol. Therefore, it was concluded that Presynch
      Ovsynch protocol could be more reproductive and beneficial when a single
      treatment with PGF2alpha was administered at 15 days postpartum (15 days after
      the PGF2alpha, Presynch-Ovsynch protocol was initiated). Interestingly, the
      administration of a GnRH agonist on Day 23 post-AI not only did not improve the
      reproductive performance of the cows receiving first postpartum timed artificial
      insemination after Presynch-Ovsynch protocol but also reduced that.

PMID- 24934376
TI  - Personalized ultrafiltration for worsening heart failure: is biological
      evaluation of plasma volume and lung ultrasound the answer?

PMID- 24934377
TI  - [Avoidance and management of complications in open surgical ureter
      reconstruction].
AB  - Open surgical reconstruction of the ureter is a urological procedure with a
      potentially high risk of complications. The correct selection of patients and
      time of operation are important aspects regarding the treatment strategy.
      Position and length of the affected ureter segment to be reconstructed determine
      the surgical intervention possibilities. The psoas hitch procedure is a well
      established technique for distal reconstruction of the ureter where most
      iatrogenic injuries occur. In more proximal or complex defects, several
      procedures are available. Partial or complete replacement of the ureter with
      bowel is still considered the standard for bridging long ureteral defects but is
      accompanied with higher intra- and postoperative complication rates. In specific
      patients and situations, autotransplantation of the kidney and subcutaneous
      pyelovesical bypasses are clinical options. Using mucosal grafts or tissue
      engineering may be new therapeutic prospects to cover ureteral defects but the
      clinical impact still needs to be clarified. All therapeutic strategies share the
      fact that great surgical expertise and experience are necessary as the operative
      technique must be mastered to avoid severe complications. 

PMID- 24934378
TI  - [Complications in percutaneous lithotomy].
AB  - BACKGROUND: Percutaneous lithotomy is the gold standard in the treatment of large
      kidney stones. Several steps of the operation might cause severe complications.
      Safe procedures depend on careful planning, accurate performance, recognition of
      problems and knowledge of how to handle them. OBJECTIVES: Relevant steps of
      percutaneous stone treatment with possible complications and their management are
      presented. MATERIALS AND METHODS: Current topics in percutaneous stone treatment
      taking into consideration the relevant literature are discussed. Furthermore,
      rare complications and strategies for safe management are presented. RESULTS:
      Careful planning and adequate preoperative diagnostic workup are essential for
      safe procedures. Puncture of the renal calyceal system and tract dilation might
      lead to severe complications. Bleeding and infectious complications are the most
      common problems. Availability of interventional radiology provides ideal
      emergency treatment in case of severe bleeding and helps to avoid surgical
      revision with high risk of organ loss. CONCLUSIONS: Percutaneous stone treatment
      is a safe and effective therapy in an experienced physician's hands. Careful
      planning and accurate performance help to avoid severe complications.

PMID- 24934379
TI  - Nonclassical dual control of circularly polarized luminescence modes of
      binaphthyl-pyrene organic fluorophores in fluidic and glassy media.
AB  - The fluorescent modes and signs of the circularly polarized luminescence of an
      axially chiral binaphthyl-pyrene organic fluorophore were successfully controlled
      by changing from a fluidic chloroform solution to a glassy poly(methyl
      methacrylate) solid film. 

PMID- 24934381
TI  - Development of a standardized laparoscopic caecum resection model to simulate
      laparoscopic appendectomy in rats.
AB  - BACKGROUND: Laparoscopic appendectomy (LA) has become one of the most common
      surgical procedures to date. To improve and standardize this technique further,
      cost-effective and reliable animal models are needed. METHODS: In a pilot study,
      30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an
      appendix vermiformis), to optimize the instrumental and surgical parameters. A
      subsequent test study was performed in another 30 rats to compare three different
      techniques for caecum resection and bowel closure. RESULTS: Bipolar coagulation
      led to an insufficiency of caecal stump closure in all operated rats (Group 1, n
      = 10). Endoloop ligation followed by bipolar coagulation and resection (Group 2,
      n = 10) or resection with a LigaSureTM device (Group 3, n = 10) resulted in
      sufficient caecal stump closure. CONCLUSIONS: We developed a LA model enabling us
      to compare three different caecum resection techniques in rats. In conclusion,
      only endoloop closure followed by bipolar coagulation proved to be a secure and
      cost-effective surgical approach.

PMID- 24934383
TI  - Powered versus manual toothbrushing for oral health.
AB  - BACKGROUND: Removing dental plaque may play a key role maintaining oral health.
      There is conflicting evidence for the relative merits of manual and powered
      toothbrushing in achieving this. This is an update of a Cochrane review first
      published in 2003, and previously updated in 2005. OBJECTIVES: To compare manual
      and powered toothbrushes in everyday use, by people of any age, in relation to
      the removal of plaque, the health of the gingivae, staining and calculus,
      dependability, adverse effects and cost. SEARCH METHODS: We searched the
      following electronic databases: the Cochrane Oral Health Group's Trials Register
      (to 23 January 2014), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE via OVID (1946 to 23
      January 2014), EMBASE via OVID (1980 to 23 January 2014) and CINAHL via EBSCO
      (1980 to 23 January 2014). We searched the US National Institutes of Health
      Trials Register and the WHO Clinical Trials Registry Platform for ongoing trials.
      No restrictions were placed on the language or date of publication when searching
      the electronic databases. SELECTION CRITERIA: Randomised controlled trials of at
      least four weeks of unsupervised powered toothbrushing versus manual
      toothbrushing for oral health in children and adults. DATA COLLECTION AND
      ANALYSIS: We used standard methodological procedures expected by The Cochrane
      Collaboration. Random-effects models were used provided there were four or more
      studies included in the meta-analysis, otherwise fixed-effect models were used.
      Data were classed as short term (one to three months) and long term (greater than
      three months). MAIN RESULTS: Fifty-six trials met the inclusion criteria; 51
      trials involving 4624 participants provided data for meta-analysis. Five trials
      were at low risk of bias, five at high and 46 at unclear risk of bias.There is
      moderate quality evidence that powered toothbrushes provide a statistically
      significant benefit compared with manual toothbrushes with regard to the
      reduction of plaque in both the short term (standardised mean difference (SMD) 
      0.50 (95% confidence interval (CI) -0.70 to -0.31); 40 trials, n = 2871) and long
      term (SMD -0.47 (95% CI -0.82 to -0.11; 14 trials, n = 978). These results
      correspond to an 11% reduction in plaque for the Quigley Hein index (Turesky) in
      the short term and 21% reduction long term. Both meta-analyses showed high levels
      of heterogeneity (I(2) = 83% and 86% respectively) that was not explained by the
      different powered toothbrush type subgroups.With regard to gingivitis, there is
      moderate quality evidence that powered toothbrushes again provide a statistically
      significant benefit when compared with manual toothbrushes both in the short term
      (SMD -0.43 (95% CI -0.60 to -0.25); 44 trials, n = 3345) and long term (SMD -0.21
      (95% CI -0.31 to -0.12); 16 trials, n = 1645). This corresponds to a 6% and 11%
      reduction in gingivitis for the Loe and Silness index respectively. Both meta
      analyses showed high levels of heterogeneity (I(2) = 82% and 51% respectively)
      that was not explained by the different powered toothbrush type subgroups.The
      number of trials for each type of powered toothbrush varied: side to side (10
      trials), counter oscillation (five trials), rotation oscillation (27 trials),
      circular (two trials), ultrasonic (seven trials), ionic (four trials) and unknown
      (five trials). The greatest body of evidence was for rotation oscillation brushes
      which demonstrated a statistically significant reduction in plaque and gingivitis
      at both time points. AUTHORS' CONCLUSIONS: Powered toothbrushes reduce plaque and
      gingivitis more than manual toothbrushing in the short and long term. The
      clinical importance of these findings remains unclear. Observation of
      methodological guidelines and greater standardisation of design would benefit
      both future trials and meta-analyses.Cost, reliability and side effects were
      inconsistently reported. Any reported side effects were localised and only
      temporary.

PMID- 24934384
TI  - Creatine for Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease is one of the most common neurodegenerative
      disorders and mitochondrial dysfunction plays an important role in its
      pathogenesis. Creatine is effective in improving mitochondrial function. It may
      therefore be useful for slowing the progression of Parkinson's disease.
      OBJECTIVES: To assess the efficacy and safety of creatine used alone or as an
      adjuvant treatment for Parkinson's disease. SEARCH METHODS: We searched the
      Cochrane Movement Disorders Group Trials Register, CENTRAL (The Cochrane Library
      2013, November Issue 4), MEDLINE (January 1966 to 10 November 2013), EMBASE (1974
      to 10 November 2013) and two Chinese databases. We searched ongoing trials
      registers and conference proceedings, checked reference lists and contacted
      authors of included trials. SELECTION CRITERIA: Randomized controlled trials
      (RCTs) comparing creatine versus placebo for Parkinson's disease. DATA COLLECTION
      AND ANALYSIS: Two review authors independently selected the trials for inclusion,
      assessed trial quality and extracted data. MAIN RESULTS: We included two RCTs
      with a total of 194 patients. Both trials compared creatine with placebo for
      Parkinson's disease and both had methodological limitations. There was no clear
      evidence of an effect on motor function (MD -0.26; 95% confidence interval (CI) 
      4.39 to 3.88, low quality evidence), activities of daily living (MD 0.37; 95% CI 
      1.28 to 2.02, low quality evidence) or quality of life after one or two years of
      treatment. One trial reported serious adverse events that were not attributed to
      creatine. Also, one trial observed higher rates of gastrointestinal effects at
      two years follow-up. AUTHORS' CONCLUSIONS: The evidence base on the effects of
      creatine in Parkinson's disease is limited by risk of bias, small sample sizes
      and short duration of the eligible trials. It does not provide a reliable basis
      on which treatment decisions can be made. Future well-designed RCTs with larger
      sample size and long-term follow-up are needed to assess creatine for Parkinson's
      disease.

PMID- 24934382
TI  - Experimental traumatic brain injury alters ethanol consumption and sensitivity.
AB  - Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead
      to significant impairments in TBI recovery. Few preclinical models have been used
      to examine alcohol use across distinct phases of the post-injury period, leaving
      mechanistic questions unanswered. To address this, the aim of this study was to
      describe the histological and behavioral outcomes of a noncontusive closed-head
      TBI in the mouse, after which sensitivity to and consumption of alcohol were
      quantified, in addition to dopaminergic signaling markers. We hypothesized that
      TBI would alter alcohol consumption patterns and related signal transduction
      pathways that were congruent to clinical observations. After midline impact to
      the skull, latency to right after injury, motor deficits, traumatic axonal
      injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid
      precursor protein (APP) accumulation was observed in white matter tracts at 6,
      24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein
      (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and
      in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7
      days, after TBI. At 14 days post-TBI, when mice were tested for ethanol
      sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain
      injured mice exhibited increased sedation time compared with uninjured mice,
      which was accompanied by deficits in striatal dopamine- and cAMP-regulated
      neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI,
      ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake
      across 7 days of consumption was significantly reduced in TBI mice compared with
      sham controls, paralleling the reduction in alcohol consumption observed
      clinically in the initial post-injury period. These data demonstrate that TBI
      increases sensitivity to ethanol-induced sedation and affects downstream
      signaling mediators of striatal dopaminergic neurotransmission while altering
      ethanol consumption. Examining TBI effects on ethanol responsitivity will improve
      our understanding of alcohol use post-TBI in humans.

PMID- 24934385
TI  - Hybrid procedure for acute stanford type a aortic dissection with aberrant right
      subclavian artery.
AB  - Aberrant right subclavian artery (ARSA) is an uncommon congenital vascular
      abnormality. Acute Stanford type A aortic dissection with ARSA is rare. We report
      a strategy for Stanford type A aortic dissection with ARSA. The ascending aorta
      and the total aortic arch were replaced and a frozen elephant trunk was implanted
      into the descending aorta. The right subclavian artery was reconstructed with the
      perfusion branch of a four-branch prosthetic graft. Two weeks later, the proximal
      part of the ARSA was sealed with a vascular plug.

PMID- 24934386
TI  - Effectiveness of spray congealing to obtain physically stabilized amorphous
      dispersions of a poorly soluble thermosensitive API.
AB  - An amorphous phase produced by micronization up to the molecular or colloidal
      level of a poorly soluble drug having low lipophilicity can distinctly enhance
      its solubility characteristics. However, though dispersing the molten mass of a
      poorly water-soluble drug within polymeric matrix has been found to be most
      effective in formation of molecular dispersions, the drug molecules which melt at
      high temperature also accompanied by decomposition, such as acetazolamide, are
      difficult to formulate as molecular dispersions. Hence, a method is proposed to
      obtain molecular dispersions of acetazolamide with poloxamer-237 by spray
      congealing under optimal heat treatment. Uniform molecular and/or colloidal
      dispersions of the drug were achieved with instantaneous solvent evaporation by
      mixing a drug solution with molten mass of the plasticizer matrix. Immobilization
      of dispersed drug molecules was effected subsequently through rapid
      solidification by spray congealing. Initial characterization of 1:1, 1:1.5, and
      1:2 ratios of solid dispersions and devitrification study of an optimized (1:2)
      ratio ensured efficacy of the proposed method in formation of physically
      stabilized amorphous systems without thermal degradation and hence resulted in
      more than ninefold rise in solubility and more than 90% dissolution within
      initial 10 min. With 1:2 ratio, molecular dispersions could be achieved by
      initial solvent evaporation stage, which when subjected to spray congealing
      produced physically stable amorphous systems, without signs of thermal
      degradation. This study also proposes an opportunity for selection of those
      polymers with which the drug is immiscible in their fluid state, yet obtaining
      molecular dispersions.

PMID- 24934387
TI  - Severe manifestations of hand-foot-genital syndrome associated with a novel
      HOXA13 mutation.
AB  - We report on a girl with absent nails, short/absent distal phalanges of the
      second to fifth fingers and toes, short thumbs, absent halluces, and carpo-tarsal
      coalition who also had genitourinary malformations. Trio-based whole exome
      sequencing identified a novel de novo mutation (c.1102A>T, p.Ile368Phe) in the
      HOXA13 gene. Heterozygous HOXA13 mutations have been previously reported in hand
      foot-genital syndrome and Guttmacher syndrome, which are variably associated with
      small nails, short distal and middle phalanges, short thumbs and halluces, but
      not absent nails. Considering the molecular data, the phenotype in the present
      patient was defined as the severe end of hand-foot-genital and Guttmacher
      syndrome spectrum. Our observation expands the clinical spectrum caused by
      heterozygous HOXA13 mutations and reinforces the difficulty of differential
      diagnosis on clinical grounds for the disorders with short distal phalanges,
      short thumbs, and short halluces.

PMID- 24934388
TI  - Using density functional theory to describe slowly varying fluctuations at finite
      temperatures: local magnetic moments in Gd and the 'not so local' moments of Ni.
AB  - We briefly describe the density functional theory (DFT)-based 'disordered local
      moment' (DLM) picture for magnetism at finite temperatures. It shows how
      relatively slowly fluctuating local moments can emerge from the interacting
      electrons of many materials. Such entities have rigid magnitudes and fluctuate
      their orientations from atomic site to atomic site on a timescale long compared
      to other electronic times. We illustrate this theory with calculations of the
      magnetocaloric effect in Gd where we find excellent agreement with experiments.
      Fluctuating moments do not appear to establish naturally over such small regions
      for some other materials. We show how the DFT-DLM theory can be extended to these
      materials with the use of the Korringa-Kohn-Rostoker nonlocal coherent potential
      approximation (KKR-NLCPA) to allow for more extensive, slow magnetic
      fluctuations. We present the first application of this approach by revisiting the
      description of the magnetic fluctuations prevalent in the paramagnetic state of
      nickel. We find that local moments can emerge above Tc and that these form
      coherently over small clumps of atomic sites (4-8 sites). 

PMID- 24934389
TI  - A readily accessible ruthenium catalyst for the solvolytic dehydrogenation of
      amine-borane adducts.
AB  - The use of the readily available complex [Ru(p-Cym)(bipy)Cl]Cl as an efficient
      and robust precatalyst for homogeneously catalysed solvolysis of amine-borane
      adducts to liberate the hydrogen content of the borane almost quantitatively is
      being presented. The reactions can be carried out in tap water, and in aqueous
      mixtures with non-deoxygenated solvents. The system is also efficient for the
      dehydrocoupling of dimethylamine-borane under solvent-free conditions. 

PMID- 24934390
TI  - Clinical Specificities in Obesity Care: The Transformations and Dissolution of
      'Will' and 'Drives'.
AB  - Public debate about who or what is to blame for the rising rates of obesity and
      overweight shifts between two extreme opinions. The first posits overweight as
      the result of a lack of individual will, the second as the outcome of bodily
      drives, potentially triggered by the environment. Even though apparently
      clashing, these positions are in fact two faces of the same liberal coin. When
      combined, drives figure as a complication on the road to health, while a strong
      will should be able to counter obesity. Either way, the body's propensity to eat
      is to be put under control. Drawing on fieldwork in several obesity clinics and
      prevention sites in the Netherlands, this paper first traces how this 'logic of
      control' presents itself in clinical practices targeted at overweight people, and
      then goes on to explore how these practices move beyond that logic. Using the
      concepts of 'will' and 'drives' as analytical tools, I sketch several modes of
      ordering reality in which bodies, subjects, food and the environment are
      configured in different ways. In this way it appears that in clinical practices
      the terms found in public discourse take on different meanings and may even lose
      all relevance. The analysis reveals a richness of practiced ideals. The paper
      argues, finally, that making visible these alternative modes of ordering opens up
      a space for normative engagements with obesity care that move beyond the logic of
      control and its critiques.

PMID- 24934391
TI  - Effects of the coronary collateral circulation on the Tp-e interval and Tp-e/QT
      ratio in patients with stable coronary artery disease.
AB  - BACKGROUND: The clinical utility of the Tp-e interval and Tp-e/QT ratio in the
      risk stratification of ventricular arrhythmic events is controversial. Therefore,
      we investigated the impact of CCC on these electrocardiographic indexes in the
      course of stable CAD. METHODS: Two hundred three consecutive patients with stable
      CAD who underwent coronary angiography and had documented total occlusion of one
      of the major coronary arteries were enrolled in this prospective cross-sectional
      study. The Tp-e interval and Tp-e/QT ratio were measured by 12-lead
      electrocardiogram. RESULTS: The Tp-e interval, cTp-e interval, Tp-e/QT ratio, and
      cTp-e/QT ratio were lower in the grade 3 CCC group compared with the others in
      all leads. Multivariate linear regression analyses was performed to identify the
      clinical factors affecting the cTp-e interval and was indicated that age (beta =
      0.261, P < 0.001), male sex (beta = 0.334, P < 0.001), poor Rentrop grade (beta =
      -0.228, P < 0.001), and NLR (beta = 0.137, P = 0.027) were independent predictors
      of a prolonged cTp-e interval. CONCLUSION: It could be concluded that the
      decreased dispersion of ventricular repolarization might contribute to the lower
      incidence of ventricular arrhythmias and SCD in CAD patients with a good CCC.

PMID- 24934393
TI  - Metabolomics: what you see is what you extract.

PMID- 24934394
TI  - Towards easy and reliable AFM tip shape determination using blind tip
      reconstruction.
AB  - Quantitative determination of the geometry of an atomic force microscope (AFM)
      probe tip is critical for robust measurements of the nanoscale properties of
      surfaces, including accurate measurement of sample features and quantification of
      tribological characteristics. Blind tip reconstruction, which determines tip
      shape from an AFM image scan without knowledge of tip or sample shape, was
      established most notably by Villarrubia [J. Res. Natl. Inst. Stand. Tech. 102
      (1997)] and has been further developed since that time. Nevertheless, the
      implementation of blind tip reconstruction for the general user to produce
      reliable and consistent estimates of tip shape has been hindered due to ambiguity
      about how to choose the key input parameters, such as tip matrix size and
      threshold value, which strongly impact the results of the tip reconstruction.
      These key parameters are investigated here via Villarrubia's blind tip
      reconstruction algorithms in which we have added the capability for users to
      systematically vary the key tip reconstruction parameters, evaluate the set of
      possible tip reconstructions, and determine the optimal tip reconstruction for a
      given sample. We demonstrate the capabilities of these algorithms through
      analysis of a set of simulated AFM images and provide practical guidelines for
      users of the blind tip reconstruction method. We present a reliable method to
      choose the threshold parameter corresponding to an optimal reconstructed tip
      shape for a given image. Specifically, we show that the trend in how the
      reconstructed tip shape varies with threshold number is so regular that the
      optimal, or Goldilocks, threshold value corresponds with the peak in the
      derivative of the RMS difference with respect to the zero threshold curve vs.
      threshold number. 

PMID- 24934395
TI  - Relationship of sodium and magnesium intakes to hypertension proven by 24-hour
      urianalysis in a South Indian population.
AB  - The Healthy Eating Asians Remain Together (HEART) study was carried out to
      investigate the relationship between 24-hour urine nutritional biomarkers and
      cardiometabolic risks in India. A total of 168 participants underwent health
      examination to assess body mass index, blood pressure, and 24-hour urine samples.
      The participants were divided into normotensive and hypertensive. The average
      blood pressure, weight, and body mass index were significantly high in patients
      considered to be hypertensive, and 24-hour urine biomarkers showed significant
      differences in sodium and magnesium/creatinine ratios in patients aged 40 and
      older. High sodium intake and reduction in magnesium consumption are associated
      with increased blood pressure in patients from India.

PMID- 24934397
TI  - Effect of fullerenol surface chemistry on nanoparticle binding-induced protein
      misfolding.
AB  - Fullerene and its derivatives with different surface chemistry have great
      potential in biomedical applications. Accordingly, it is important to delineate
      the impact of these carbon-based nanoparticles on protein structure, dynamics,
      and subsequently function. Here, we focused on the effect of hydroxylation - a
      common strategy for solubilizing and functionalizing fullerene - on protein
      nanoparticle interactions using a model protein, ubiquitin. We applied a set of
      complementary computational modeling methods, including docking and molecular
      dynamics simulations with both explicit and implicit solvent, to illustrate the
      impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We
      found that all derivatives bound to the model protein. Specifically, the more
      hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the
      surface of the protein via hydrogen bonds, which stabilized the protein without
      inducing large conformational changes in the protein structure. In contrast,
      fullerene derivatives with a smaller number of hydroxyl groups buried their
      hydrophobic surface inside the protein, thereby causing protein denaturation.
      Overall, our results revealed a distinct role of surface chemistry on
      nanoparticle-protein binding and binding-induced protein misfolding. 

PMID- 24934396
TI  - Relationships among attention function, exercise, and body mass index: a
      comparison between young breast cancer survivors and acquaintance controls.
AB  - OBJECTIVE: Although regular physical activity is associated with lower all-cause
      and disease-specific mortality among breast cancer survivors (BCS), most BCS do
      not meet its recommended guidelines. Attention function, a domain of cognition,
      is essential for daily tasks such as exercising, a form of planned physical
      activity. We tested the hypotheses that lower self-reported attention function in
      BCS would be associated with less exercise and higher body mass index (BMI) by
      comparing a group of 505 young BCS (45 years or younger at diagnosis and 3-8
      years post-treatment) with 466 acquaintance controls (AC). METHODS: The groups
      were compared on self-reported physical and psychological outcomes. Mplus
      software was used to perform confirmatory structural equation modeling with a
      robust maximum likelihood estimator to evaluate hypothesized relationships among
      variables. The criteria for good model fit were having root mean square error of
      approximation (RMSEA) < 0.06, comparative fit index (CFI) > 0.95, and
      standardized root mean square residual (SRMR) < 0.08. Modification indices were
      used to better fit the model. RESULTS: The final model demonstrated good fit,
      with RMSEA = 0.05, CFI = 0.98, and SRMR = 0.03. After controlling for
      demographics, parameter estimates revealed that, compared with AC, young BCS
      reported worse attention function (p < 0.001), more depressive symptoms (p <
      0.001), and more fatigue (p < 0.001). Controlling for fatigue, depression, and
      anxiety, better attention function was associated with a greater likelihood of
      exercise in the past 3 months (p = 0.039), which in turn was associated with a
      lower BMI (p < 0.001). CONCLUSIONS: The significant association between attention
      function and physical activity, if confirmed in a longitudinal study, will
      provide new targets for interventions aimed at improving physical activity and
      decreasing BMI among BCS.

PMID- 24934398
TI  - Financial aspects of veterinary herd health management programmes.
AB  - Veterinary herd health management (VHHM) programmes have been shown to be
      economically effective in the past. However, no current information is available
      on costs and benefits of these programmes. This study compared economics and farm
      performance between participants and non-participants in VHHM programmes in 1013
      dairy farms with over 40 cows. Milk Production Registration (MPR) data and a
      questionnaire concerning VHHM were used. Based on the level of participation in
      VHHM (as indicated in the questionnaire), costs of the programmes were calculated
      using a normative model. The economic value of the production effects was
      similarly calculated using normative modelling based on MPR data. Participants in
      VHHM had a better performance with regard to production, but not with regard to
      reproduction. Over 90 per cent of the VHHM participants were visited at least
      once every six weeks and most participants discussed at least three topics. In
      most farms, the veterinarian did the pregnancy checks as part of the VHHM
      programmes. There was a benefit to cost ratio of about five per cow per year for
      VHHM participants, and a mean difference in net returns of ?30 per cow per year
      after adjusting for the cost of the programme. This portrays that participation
      in a VHHM programme is cost-efficient. There is, however, much unexplained
      variation in the net returns, possibly due to diverse approaches by veterinarians
      towards VHHM or by other factors not included in this analysis, like nutritional
      quality or management abilities of the farmer. 

PMID- 24934399
TI  - Spread of Cryptosporidium baileyi in red grouse Lagopus lagopus scoticus.

PMID- 24934400
TI  - The neonatologist's role in pediatric anesthesia neurotoxicity.

PMID- 24934401
TI  - Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized
      controlled trial in children and adolescents with autism.
AB  - BACKGROUND: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off
      label for children with autism. To date, clinical trials examining the use of
      SSRIs in autism have been limited by small sample sizes and inconclusive results.
      The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be
      adequately examined to provide evidence to support current clinical practice. The
      aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the
      efficacy and safety of low dose fluoxetine compared with placebo, for reducing
      the frequency and severity of repetitive stereotypic behaviors in children and
      adolescents with an autism spectrum disorder (ASD). The relationship between the
      effectiveness of fluoxetine treatment and serotonin transporter genotype will
      also be explored. METHODS/DESIGN: The FAB study is a multicenter, double-blinded,
      randomized controlled trial, funded by the Australian Government's National
      Health and Medical Research Council (NHMRC) grant. Participants will be aged
      between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants
      will be randomized to either placebo or fluoxetine for a 16-week period.
      Medication will be titrated over the first four weeks. Reponses to medication
      will be monitored fortnightly using the Clinical Global Impressions Scale (CGI).
      The primary outcome measure is the Children's Yale-Brown Obsessive Compulsive
      Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered
      at baseline and 16 weeks. Secondary outcome measures include the Aberrant
      Behaviour Scale (ABC), the Spence Children's Anxiety Scale Parent Report (SCAS
      P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16
      weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele
      variants using a cheek swab. Continuous outcomes, including the primary outcome
      will be compared between the active and placebo groups using unadjusted linear
      regression. Binary outcomes will be compared using unadjusted logistic
      regression. DISCUSSION: The FAB study is a large clinical trial to specifically
      investigate the efficacy of low dose fluoxetine for restricted, repetitive, and
      stereotyped behaviors in ASD. The outcomes of this study will contribute to
      evidence-based interventions used in clinical practice to assist children with
      ASD. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12608000173392; registered on 9 April, 2008.

PMID- 24934402
TI  - Immune regulation by intralymphatic immunotherapy with modular allergen
      translocation MAT vaccine.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) faces problems related to side
      effects and limited efficacy. Direct administration of allergen extracts into
      lymph nodes induces increased specific IgG production and T-cell responses using
      significantly lower allergen doses. METHODS: In this study, mechanisms of immune
      regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis
      patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1
      vaccine, were investigated in PBMC and cell cultures for specific T-cell
      proliferation, Fel d 1-tetramer-specific responses, and multiple immune
      regulatory molecules. RESULTS: MAT-Fel d 1 vaccine was efficiently internalized
      by antigen-presenting cells. This was followed by precaspase 1 cleavage to
      caspase 1 and secretion of IL-1beta, indicating inflammasome activation. Mat-Fel
      d 1 induced specific T-cell proliferation and an IL-10- and IFN-gamma-dominated T
      cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d
      1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms
      of immune suppression. Early Fel d 1-specific T-cell activation was followed by
      full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group,
      characterized by increased allergen-specific T regulatory cells, decreased
      circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3
      expression, and change in the HR2/HR1 ratio toward HR2. CONCLUSIONS: This study
      demonstrates the induction of allergen tolerance after 3 intra-lymph node
      injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization
      of the allergen, activation of inflammasome, and generation of allergen-specific
      peripheral T-cell tolerance.

PMID- 24934403
TI  - Desvenlafaxine prevents white matter injury and improves the decreased
      phosphorylation of the rate-limiting enzyme of cholesterol synthesis in a chronic
      mouse model of depression.
AB  - Serotonin/norepinephrine reuptake inhibitors antidepressants exert their effects
      by increasing serotonin and norepinephrine in the synaptic cleft. Studies show it
      takes 2-3 weeks for the mood-enhancing effects, which indicate other mechanisms
      may underlie their treatment effects. Here, we investigated the role of white
      matter in treatment and pathogenesis of depression using an unpredictable chronic
      mild stress (UCMS) mouse model. Desvenlafaxine (DVS) was orally administrated to
      UCMS mice at the dose of 10 mg/kg/day 1 week before they went through a 7-week
      stress procedure and lasted for over 8 weeks before the mice were killed. No
      significant changes were found for protein markers of neurons and astrocytes in
      UCMS mice. However, myelin and oligodendrocyte-related proteins were
      significantly reduced in UCMS mice. DVS prevented the stress-induced injury to
      white matter and the decrease of phosphorylated 5'-AMP-activated protein kinase
      and 3-hydroxy-3-methyl-glutaryl-CoA reductase protein expression. DVS increased
      open arm entries in an elevated plus-maze test, sucrose consumption in the
      sucrose preference test and decreased immobility in tail suspension and forced
      swimming tests. These findings suggest that stress induces depression-like
      behaviors and white matter deficits in UCMS mice. DVS may ameliorate the
      oligodendrocyte dysfunction by affecting cholesterol synthesis, alleviating the
      depression-like phenotypes in these mice. We examined the possible role of
      oligodendrocyte and myelin in the pathological changes of depression with an
      unpredictable chronic mild stress (UCMS) mouse model. Oligodendrocyte-related
      proteins in the mouse brain were specifically changed during the stress period.
      The depressive-like behaviors and oligodendrocyte deficits could be prevented by
      the administration of desvenlafaxine. Oligodendrocyte and myelin may be an
      essential target of desvenlafaxine for the treatment of depression. 

PMID- 24934405
TI  - Splanchnic Tissue Oxygenation for Predicting Feeding Tolerance in Preterm
      Infants.
AB  - BACKGROUND: Feeding intolerance is very frequent in preterm infants, and the
      development of an early effective biomarker for its prediction could be useful
      for carrying out a proper feeding strategy. Our aim was to evaluate if the
      measurement of splanchnic regional oxygenation (rSO2S) and splanchnic fractional
      oxygen extraction ratio (FOES) using near-infrared spectroscopy (NIRS) is
      correlated with the time needed to achieve full enteral feeding and if it can
      predict the development of feeding intolerance. MATERIALS AND METHODS: We
      measured rSO2S and FOES in preterm infants 25 +/- 0 to 31 +/- 6 weeks of
      gestational age at 24-72 hours of life during continuous enteral feeding.
      RESULTS: Linear regression analysis did not evidence any relationship between
      rSO2S and FOES and the time for achievement of full enteral feeding. Multivariate
      logistic regression analysis showed that birth weight <1000 g (relative risk
      [RR], 4.5; 95% confidence interval [CI], 1.23-16.45) and patent ductus arteriosus
      occurrence (RR, 9.3; 95% CI, 1.31-66.06) increased the risk of developing feeding
      intolerance in our population. CONCLUSION: Splanchnic oxygenation and oxygen
      extraction measured in the first days of life are not correlated with the time
      needed to achieve full enteral feeding in preterm infants receiving continuous
      enteral nutrition.

PMID- 24934404
TI  - Association of candidate gene polymorphisms and TGF-beta/IL-10 levels with
      malaria in three regions of Cameroon: a case-control study.
AB  - BACKGROUND: Plasmodium falciparum malaria is one of the most widespread and
      deadliest infectious diseases in children under five years in endemic areas. The
      disease has been a strong force for evolutionary selection in the human genome,
      and uncovering the critical host genetic factors that confer resistance to the
      disease would provide clues to the molecular basis of protective immunity and
      improve vaccine development initiatives. METHODS: The effect of single nucleotide
      polymorphisms (SNPs) and plasma transforming growth factor beta (TGF-beta) and
      interleukin 10 (IL-10) levels on malaria pathology was investigated in a case
      control study of 1862 individuals from two major ethnic groups in three regions
      with intense perennial P. falciparum transmission in Cameroon. Thirty-four
      malaria candidate polymorphisms, including the sickle cell trait (HbS), were
      assayed on the Sequenom iPLEX platform while plasma TGF-beta and IL-10 levels
      were measured by sandwich ELISA. RESULTS: The study confirms the known protective
      effect of HbS against severe malaria and also reveals a protective effect of SNPs
      in the nitrogen oxide synthase 2 (NOS2) gene against malaria infection, anaemia
      and uncomplicated malaria. Furthermore, ADCY9 rs10775349 (additive G) and ABO
      rs8176746 AC individuals were associated with protection from hyperpyrexia and
      hyperparasitaemia, respectively. Meanwhile, individuals with the EMR1 rs373533
      GT, EMR1 rs461645 CT and RTN3 rs542998 (additive C) genotypes were more
      susceptible to hyperpyrexia while both females and males with the rs1050828 and
      rs1050829 SNPs of G6PD, respectively, were more vulnerable to anaemia. Plasma TGF
      beta levels were strongly correlated with heterozygosity for the ADCY9 rs2230739
      and HBB rs334 SNPs while individuals with the ABO rs8176746 AC genotype had lower
      IL-10 levels. CONCLUSION: Taken together, this study suggests that some rare
      polymorphisms in candidate genes may have important implications for the
      susceptibility of Cameroonians to severe malaria. Moreover using the
      uncomplicated malaria phenotype may permit the identification of novel pathways
      in the early development of the disease.

PMID- 24934406
TI  - Embryonic stem cells improve skeletal muscle recovery after extreme atrophy in
      mice.
AB  - INTRODUCTION: We injected embryonic stem cells into mouse tibialis anterior
      muscles subjected to botulinum toxin injections as a model for reversible
      neurogenic atrophy. METHODS: Muscles were exposed to botulinum toxin for 4 weeks
      and allowed to recover for up to 6 weeks. At the onset of recovery, a single
      muscle injection of embryonic stem cells was administered. The myofiber cross
      sectional area, single twitch force, peak tetanic force, time-to-peak force, and
      half-relaxation time were determined. RESULTS: Although the stem cell injection
      did not affect the myofiber cross-sectional area gain in recovering muscles, most
      functional parameters improved significantly compared with those of recovering
      muscles that did not receive the stem cell injection. CONCLUSIONS: Muscle
      function recovery was accelerated by embryonic stem cell delivery in this durable
      neurogenic atrophy model. We conclude that stem cells should be considered a
      potential therapeutic tool for recovery after extreme skeletal muscle atrophy.

PMID- 24934407
TI  - Long hours locum doctor is struck off after failing to address shortcomings.

PMID- 24934409
TI  - Variable access to quality nutrition information regarding inflammatory bowel
      disease: a survey of patients and health professionals and objective examination
      of written information.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) report a range of
      nutritional and dietary problems and high-quality written information should be
      available on these. There is little research investigating the availability and
      quality of such information for patients with IBD. OBJECTIVE: This study assessed
      the type and quality of written information on nutrition and diet available to
      patients with IBD and the opinions of patients and health professionals. SETTING
      AND PARTICIPANTS: Seventy-two patients with IBD were recruited from a large
      gastroenterology outpatient centre in England. One hundred dietitians from across
      the United Kingdom were also recruited. METHODS: Face-to-face surveys were
      conducted with patients with IBD. Questions regarding the use, format and
      usefulness of dietary information received were probed. Dietitians were surveyed
      regarding written dietary information used in clinical practice. Samples of IBD
      specific dietary information used across the UK were objectively assessed using
      two validated tools. MAIN RESULTS: The majority of patients rated written
      information as 'good' or 'very good', with the most useful information relating
      to 'general diet and IBD'. Forty-nine (49%) dietitians reported gaps in written
      information available for patients with IBD. Fifty-three different samples of IBD
      specific information sheets were returned, with widely variable objective quality
      ratings. Commercially produced written information scored greater than locally
      produced information (BMA tool, P < 0.05). CONCLUSIONS: Patient access to high
      quality, written, IBD-specific dietary information is variable. IBD-specific
      written nutrition information needs to be developed in accordance with validated
      tools to empower patients, encourage self-management and overcome nutritional
      implications of IBD.

PMID- 24934410
TI  - Diabetes mellitus increases the risk of early gastric cancer development.
AB  - BACKGROUND: The significance of diabetes mellitus (DM) in gastric carcinogenesis
      still remains unclear. We investigated whether DM would be a risk factor for the
      development of early gastric cancer. METHODS: Factors related to the presence of
      gastric cancer were examined in patients undergoing medical health checkups. We
      then investigated whether DM was related to the development of early gastric
      cancer during an endoscopic follow-up study. RESULTS: Gastric cancer was detected
      in 14 (1.0%) of 1463 patients at the first endoscopic examination and was
      significantly associated with the severity of gastric atrophy and the presence of
      DM. During the follow-up period (range 36-108 months; mean 70.0 months), early
      gastric cancer was newly detected in 26 (1.8%) of the 1449 patients in whom
      gastric cancer had not been detected at the first examination. Gastric cancer was
      detected in 17 (1.3%) of 1301 patients without DM, and in 9 (6.1%) of 148
      patients with DM (P < 0.0001). Multivariate analyses demonstrated that open-type
      gastric atrophy and DM were independently related to the development of early
      gastric cancer (P < 0.0001 and P = 0.020, respectively). Gastric cancer was
      identified in 14 (5.1%) of 274 patients who had open-type atrophic gastritis
      without DM, whereas it was identified in 8 (16.0%) of 50 patients who had both
      open-type atrophic gastritis and DM (P = 0.0042). CONCLUSION: DM increases the
      risk of early gastric cancer development.

PMID- 24934408
TI  - Synthetic lethality in ATM-deficient RAD50-mutant tumors underlies outlier
      response to cancer therapy.
AB  - Metastatic solid tumors are almost invariably fatal. Patients with disseminated
      small-cell cancers have a particularly unfavorable prognosis, with most
      succumbing to their disease within two years. Here, we report on the genetic and
      functional analysis of an outlier curative response of a patient with metastatic
      small-cell cancer to combined checkpoint kinase 1 (CHK1) inhibition and DNA
      damaging chemotherapy. Whole-genome sequencing revealed a clonal hemizygous
      mutation in the Mre11 complex gene RAD50 that attenuated ATM signaling which in
      the context of CHK1 inhibition contributed, via synthetic lethality, to extreme
      sensitivity to irinotecan. As Mre11 mutations occur in a diversity of human
      tumors, the results suggest a tumor-specific combination therapy strategy in
      which checkpoint inhibition in combination with DNA-damaging chemotherapy is
      synthetically lethal in tumor cells but not normal cells with somatic mutations
      that impair Mre11 complex function. SIGNIFICANCE: Strategies to effect deep and
      lasting responses to cancer therapy in patients with metastatic disease have
      remained difficult to attain, especially in early-phase clinical trials. Here, we
      present an in-depth genomic and functional genetic analysis identifying RAD50
      hypomorphism as a contributing factor to a curative response to systemic
      combination therapy in a patient with recurrent, metastatic small-cell cancer.

PMID- 24934411
TI  - Age and gender differences in the prevalence and patterns of multimorbidity in
      the older population.
AB  - BACKGROUND: The coexistence of several chronic diseases in one same individual,
      known as multimorbidity, is an important challenge facing health care systems in
      developed countries. Recent studies have revealed the existence of multimorbidity
      patterns clustering systematically associated distinct clinical entities. We
      sought to describe age and gender differences in the prevalence and patterns of
      multimorbidity in men and women over 65 years. METHODS: Observational
      retrospective multicentre study based on diagnostic information gathered from
      electronic medical records of 19 primary care centres in Aragon and Catalonia.
      Multimorbidity patterns were identified through exploratory factor analysis. We
      performed a descriptive analysis of previously obtained patterns (i.e.
      cardiometabolic (CM), mechanical (MEC) and psychogeriatric (PG)) and the diseases
      included in the patterns stratifying by sex and age group. RESULTS: 67.5% of the
      aged population suffered two or more chronic diseases. 32.2% of men and 45.3% of
      women were assigned to at least one specific pattern of multimorbidity, and 4.6%
      of men and 8% of women presented more than one pattern simultaneously. Among
      women over 65 years the most frequent pattern was the MEC pattern (33.3%),
      whereas among men it was the CM pattern (21.2%). While the prevalence of the CM
      and MEC patterns decreased with age, the PG pattern showed a higher prevalence in
      the older age groups. CONCLUSIONS: Significant gender differences were observed
      in the prevalence of multimorbidity patterns, women showing a higher prevalence
      of the MEC and PG patterns, as well as a higher degree of pattern overlapping,
      probably due to a higher life expectancy and/or worse health. Future studies on
      multimorbidity patterns should take into account these differences and,
      therefore, the study of multimorbidity and its impact should be stratified by age
      and sex.

PMID- 24934412
TI  - Posterior tibial artery aneurysm: a case report with review of literature.
AB  - BACKGROUND: Aneurysms infra-patellar region are uncommon. Of them, true aneurysms
      are very rare and that of posterior tibial artery are extremely rare. The more
      common, pseudoaneurysms are commonly associated with trauma whereas the true ones
      are linked with either inflammatory or mycotic origins. CASE PRESENTATION: We
      reported another case of true aneurysm of posterior tibial artery without any
      evident aetiology. This was repaired with resection of aneurysm followed by
      interposition vein graft. CONCLUSION: Through this report, we discussed the
      rarity, review of literature and management of this unusual condition.

PMID- 24934413
TI  - Cystic olfactory ensheathing cell tumor: a case report.

PMID- 24934414
TI  - Treatment of olfactory neuroblastoma: a new approach.

PMID- 24934416
TI  - Applying latent semantic analysis to large-scale medical image databases.
AB  - Latent Semantic Analysis (LSA) although has been used successfully in text
      retrieval when applied to CBIR induces scalability issues with large image
      collections. The method so far has been used with small collections due to the
      high cost of storage and computational time for solving the SVD problem for a
      large and dense feature matrix. Here we present an effective and efficient
      approach of applying LSA skipping the SVD solution of the feature matrix and
      overcoming in this way the deficiencies of the method with large scale datasets.
      Early and late fusion techniques are tested and their performance is calculated.
      The study demonstrates that early fusion of several composite descriptors with
      visual words increase retrieval effectiveness. It also combines well in a late
      fusion for mixed (textual and visual) ad hoc and modality classification. The
      results reported are comparable to state of the art algorithms without including
      additional knowledge from the medical domain. 

PMID- 24934417
TI  - Relationship between organizational justice and organizational safety climate: do
      fairness perceptions influence employee safety behaviour?
AB  - This study investigated the relationships between organizational justice,
      organizational safety climate, job satisfaction, safety compliance and accident
      frequency. Ghanaian industrial workers participated in the study (N = 320).
      Safety climate and justice perceptions were assessed with Hayes, Parender,
      Smecko, et al.'s (1998) and Blader and Tyler's (2003) scales respectively. A
      median split was performed to dichotomize participants into 2 categories: workers
      with positive and workers with negative justice perceptions. Confirmatory factors
      analysis confirmed the 5-factor structure of the safety scale. Regression
      analyses and t tests indicated that workers with positive fairness perceptions
      had constructive perspectives regarding workplace safety, expressed greater job
      satisfaction, were more compliant with safety policies and registered lower
      accident rates. These findings provide evidence that the perceived level of
      fairness in an organization is closely associated with workplace safety
      perception and other organizational factors which are important for safety. The
      implications for safety research are discussed. 

PMID- 24934418
TI  - Organizational factors affecting safety implementation in food companies in
      Thailand.
AB  - Thai food industry employs a massive number of skilled and unskilled workers.
      This may result in an industry with high incidences and accident rates. To
      improve safety and reduce the accident figures, this paper investigates factors
      influencing safety implementation in small, medium, and large food companies in
      Thailand. Five factors, i.e., management commitment, stakeholders' role, safety
      information and communication, supportive environment, and risk, are found
      important in helping to improve safety implementation. The statistical analyses
      also reveal that small, medium, and large food companies hold similar opinions on
      the risk factor, but bear different perceptions on the other 4 factors. It is
      also found that to improve safety implementation, the perceptions of safety
      goals, communication, feedback, safety resources, and supervision should be
      aligned in small, medium, and large companies. 

PMID- 24934419
TI  - Understanding expectations of different user groups of a sophisticated fall
      detection system.
AB  - The evaluation in technical invention is important because it tests functionality
      of the intervention and it forms an overall point of view of a user. This study
      aims to introduce an approach for collecting user expectations with Q methodology
      in Safe Private Home for Elderly Persons (CARE), which is a new development in
      ambient assisted living. CARE is a sophisticated fall detection system used in
      elderly homes to monitor elderly people and the staff. Expectations of elderly
      people and the staff were collected with Q sorting. Requirements of examined
      groups were explored successfully on the basis of the sorting and the differences
      in their opinions were appointed. 

PMID- 24934420
TI  - Applying hierarchical loglinear models to nonfatal underground coal mine
      accidents for safety management.
AB  - Underground mining is considered to be one of the most dangerous industries and
      mining remains the most hazardous occupation. Categorical analysis of accident
      records may present valuable information for preventing accidents. In this study,
      hierarchical loglinear analysis was applied to occupational injuries that
      occurred in an underground coal mine. The main factors affecting the accidents
      were defined as occupation, area, reason, accident time and part of body
      affected. By considering subfactors of the main factors, multiway contingency
      tables were prepared and, thus, the probabilities that might affect nonfatal
      injuries were investigated. At the end of the study, important accident risk
      factors and job groups with a high probability of being exposed to those risk
      factors were determined. This article presents important information on
      decreasing the number accidents in underground coal mines. 

PMID- 24934421
TI  - Paradigms and safety requirements for a new generation of workplace equipment.
AB  - A workplace in the manufacturing industry consists of not only stationary
      equipment (e.g., machining centres, fixed robots) but also mobile equipment
      (e.g., automated guided vehicles, mobile robots), with both kinds cooperating
      directly with workers. Workplace equipment should not only be safe, it should
      also not generate fear or anxiety; still better if it should inspire calm and
      confidence. In view of robot laws, this article presents selected examples of
      robot-human co-operation, reviews safety requirements and safety functions
      developed to date. It also proposes a package of selected new safety functions,
      necessary to fulfil this paradigm. It also suggests and presents examples of
      actions that can make the workplace a human-friendly environment and presents
      examples of such actions. 

PMID- 24934422
TI  - Optimizing noise control strategy in a forging workshop.
AB  - In this paper, a computer program based on a genetic algorithm is developed to
      find an economic solution for noise control in a forging workshop. Initially,
      input data, including characteristics of sound sources, human exposure, abatement
      techniques, and production plans are inserted into the model. Using sound
      pressure levels at working locations, the operators who are at higher risk are
      identified and picked out for the next step. The program is devised in MATLAB
      such that the parameters can be easily defined and changed for comparison. The
      final results are structured into 4 sections that specify an appropriate
      abatement method for each operator and machine, minimum allowance time for high
      risk operators, required damping material for enclosures, and minimum total cost
      of these treatments. The validity of input data in addition to proper settings in
      the optimization model ensures the final solution is practical and economically
      reasonable. 

PMID- 24934423
TI  - Occupational cognitive failure and its relationship with unsafe behaviors and
      accidents.
AB  - OBJECTIVES: The aim of this study was to assess the relationship between
      occupational cognitive failures (OCFs) and unsafe behaviors, accidents and
      driving offences among municipal bus drivers in Tehran, Iran. METHODS: Systematic
      random sampling was used to select 190 drivers from 3 transport and traffic
      Tehran districts. Data were collected with the occupational cognitive failure
      questionnaire (OCFQ), the driver behavior questionnaire and a data collection
      form. RESULTS: The mean (SD) numbers of driving-related offences and road traffic
      accidents were 1.5 (2.6) and 0.37 (1.0), respectively. The mean (SD) numbers of
      deliberate driving violations, unintended violations, driving slips and mistakes
      were 6.97 (5.5), 1.61 (1.5), 13.6 (9.0) and 4.53 (3.28), respectively. The mean
      (SD) number of the OCFs was 28.9 (20.5). A significant correlation was found
      between occupational cognitive error and unsafe driving behavior subscales. The
      stepwise logistic regression results showed that, while controlling the effects
      of confounding factors, the OCF predicts 6%, 9%, 15% and 9% of deliberate
      violations, unintended violations, driving slips and driving mistakes,
      respectively. CONCLUSION: The results of this study show that the score of the
      OCFQ is a predictor of unsafe driving behaviors and its subscales.

PMID- 24934424
TI  - Evaluating workers' exposure to metalworking fluids and effective factors in
      their dispersion in a car manufacturing factory.
AB  - INTRODUCTION: Metalworking fluids (MWFs), which are widely used in metal working
      operations, can cause different adverse effects, e.g., dermal and respiratory
      disorders, and cancer. Evaluating workers' exposure to MWF mists and the
      effective factors in their dispersion were the purpose of this study. MATERIALS
      AND METHOD: Seventy-five out of 300 workers working in metalworking workshops
      were randomly selected. MWF concentrations were measured with the National
      Institute for Occupational Safety and Health (NIOSH) 5524 method. Air temperature
      and velocity were also determined as the predicted effective parameters on the
      level of exposure. RESULTS: The results indicated that exposure to MWF mists in
      one workshop was higher than in the other ones (p < .05). The findings also
      showed that temperature was an effective factor in the dispersion of MWF mists (p
      < .05). DISCUSSION: The exposure of almost all workers was under the threshold
      limit value of 5 mg/m(3), but it was over the value recommended by NIOSH of 0.5
      mg/m(3). Air temperature was an effective factor in workers' exposure (r = .576).

PMID- 24934425
TI  - A thermal stress treadmill walk for clinic evaluation of candidates for hazardous
      materials (HazMat) duty.
AB  - U.S. guidance for examining hazmat workers recommends stress testing be
      considered when heat stress is expected. However, the most common stress test
      Bruce protocol treadmill electrocardiography (BPTE) wearing gym clothes-creates
      little thermal stress. OBJECTIVE: Evaluate a novel thermal stress treadmill walk
      (TSTW). METHODS: Body temperatures and heart rates during BPTE in 93 current and
      potential hazmat workers wearing gym clothes were compared with later values in
      35 of these subjects while they were wearing thermally-restrictive "sauna suits"
      during a 45-min TSTW. Physiological strain index (PSI) was calculated from
      temperature and heart rate changes and compared with PSI values from hazmat
      simulations and climatic chamber exercises. RESULTS: Tympanic temperature (TT)
      rose 0.5 degrees C (SD 0.5) during BPTE lasting 12.4 min (SD 2.9). PSI reached
      6.0 (SD 1.3). TT rose 1.0 degrees C (SD 0.5) during TSTW, p < .01. PSI averaged
      6.6 (SD 1.9) in 29 subjects who completed TSTW, versus 5.7 (SD 5.7) in the 6
      subjects who did not. Ingested thermistor temperatures increased more than did TT
      during TSTW, yielding PSI of 7.0 (SD 1.5), equal to PSI values from climatic
      chamber exercises, i.e., 7.0 (SD 1.0). CONCLUSION: TSTW increased body
      temperature and PSI in 29 of the 35 subjects who completed it to levels matching
      those of operational simulations in climatic chambers and during hazmat
      exercises. This TSTW may be useful for evaluating candidates for hazmat duty.

PMID- 24934426
TI  - Variability of musculoskeletal strain on dentists: an electromyographic and
      goniometric study.
AB  - INTRODUCTION: Dentists and hygienists are strongly affected by musculoskeletal
      disorders (MSDs). As workstation concepts are supported by subjective arguments
      only, the aim of this study was to use objective measurements to compare the
      variability of strain in various concepts: a dental chair equipped with a cart or
      an over-the-patient delivery system without an assistant, and Dr Daryl Beach's
      concept with an assistant. METHODS: Goniometric and electromyographic recordings
      were made on 8 subjects, during a scaling operation. The electrical activity of
      their trapezius and lumbar muscles was compared, as were their cervical and
      lumbar ranges of motion. RESULTS: The results showed that there was a wide
      variability depending on the workstation. However, the Beach concept tended to
      reduce physical strain on most parameters: duration of left lumbar muscle
      activity (2% compared to 15% of time spent in > 10% maximal voluntary
      contraction, MVC), time spent in cervical side bending (4% compared to 30%),
      cervical flexion of > 20 degrees  (9% compared to 40%), and left trapezius
      activity (9% of time spent > 10% MVC compared to 28%). CONCLUSION: Practitioners
      and students should adjust their workstations to reduce the prevalence of MSDs.

PMID- 24934427
TI  - Self-rated physical loads of work tasks among firefighters.
AB  - OBJECTIVES: The present study sought to identify firefighters' rated physical
      demands for the most frequently occurring work tasks and to determine if the
      ratings differed between full-time and part-time firefighters to help create a
      basis for the development of physical employment tests for firefighters. METHODS:
      An extensive questionnaire was completed by 125 and 68 firefighters in 2000 and
      2010, respectively. The data were analysed with the Mann-Whitney U test and
      binominal test and ranked on the basis of the responses in each category.
      RESULTS: Significant differences were seen between the full- and part-time
      firefighters. The work tasks rated as the most physically strenuous in terms of
      aerobic fitness, muscle strength, work posture and body control by most
      respondents were smoke diving upstairs (carrying a hose), victim rescue in
      different ways, carrying a stretcher over terrain and pulling a hose.
      CONCLUSIONS: Physically strenuous work tasks should be included in the end-point
      performance variables used to select physical performance tests for firefighters.
      The part-time firefighters with no experience in several of the work tasks
      suggests that work-related exercises are important if both groups of firefighters
      are expected to do similar work.

PMID- 24934428
TI  - Health and safety perception of workers in Turkey: a survey of construction
      sites.
AB  - This study reports the general health and safety (HS) conditions in the Turkish
      construction industry from the perspective of construction labor. Toward this
      aim, a questionnaire survey was carried out with 800 workers employed in 32
      construction projects in Turkey. Contractors were found to neglect their legal
      liabilities in paying workers' insurance premiums. Also, they overlooked safety
      training and were reluctant to hiring physicians at construction sites and
      investing in personal protective equipment (PPE). As the real constructors of
      projects, workers did not attach adequate importance to occupational training. In
      addition, they were not willing to use some PPE. Key participants of HS affairs
      such as workers, contractors, unions, and government should comprehend their
      drawbacks to overcome the current dangerous view of the industry. In this regard,
      related government bodies should compel contractors and workers to adapt to the
      relatively new regulations on occupational HS. 

PMID- 24934429
TI  - Effect of different types of rest-break interventions on neck and shoulder muscle
      activity, perceived discomfort and productivity in symptomatic VDU operators: a
      randomized controlled trial.
AB  - OBJECTIVE: This study evaluated the effect of different types of activities
      during rest-break interventions on neck and shoulder muscle activity, muscle
      discomfort and productivity among symptomatic video display unit (VDU) operators
      performing prolonged computer terminal work. STUDY DESIGN AND SETTING: Randomized
      controlled trial was used. Thirty symptomatic VDU operators were randomly
      assigned to 2 active break groups (stretching and dynamic movement) and a
      reference group. The subjects performed the same typing task for 60 min and
      received 3-min breaks after each 20 min of work. Root mean square and median
      frequency were calculated for neck and shoulder muscle activity. Muscle
      discomfort was measured with Borg's CR-10 scale. Productivity was measured by
      counting words. RESULTS: There were no significant differences between the types
      of activities during breaks on neck and shoulder muscle activity, muscle
      discomfort or productivity. However, there was a significant difference in the
      level of muscle discomfort over time. CONCLUSIONS: Three types of activity during
      breaks showed a favourable effect on neck and shoulder muscle activity and
      productivity, and a positive effect on muscle discomfort in symptomatic VDU
      operators.

PMID- 24934430
TI  - Psychosocial and individual characteristics and musculoskeletal complaints among
      clinical laboratory workers.
AB  - Musculoskeletal disorders (MSDs) are an important health problem among healthcare
      workers, including clinical laboratory ones. The aim of the present study was to
      investigate the prevalence of MSDs and individual and psychosocial risk factors
      among clinical laboratory workers. A cross-sectional study was carried out among
      156 workers of 30 clinical laboratories in 3 towns of Iran. The Nordic
      questionnaire with individual and psychosocial risk factors was used to collect
      data. Multiple logistic regression analysis was performed. The prevalence of
      reported MSDs among the study population was 72.4% in the past 12 months. The
      most prevalent MSDs were pain in the lower back and neck; 42.7% and 33.3%,
      respectively. Significant relations were found between MSDs and age, gender,
      heavy work at home and job control (p < .05). MSDs among laboratory workers were
      high and associated with age, gender, heavy work at home and job control. More
      research into measuring these factors and workplace physical demands is
      suggested. 

PMID- 24934431
TI  - Work-related musculoskeletal disorders, job stressors and gender responses in
      foundry industry.
AB  - The main aim of this paper was to identify job stressors, gender responses and
      association of psychosocial work stressors with prevalence of work related
      musculoskeletal disorders (MSDs) among foundry workers. The data were obtained
      with ergonomics checklist using Likert scale. The results of this study showed a
      high prevalence of MSDs among workers. The male workers were more prone to pain
      in neck while the female workers were more prone to MSDs in upper back and
      shoulders. Correlation analysis showed significant relationship of dimensions of
      work aspects with pain and discomfort. It proved that the work-related MSDs are
      the results of interaction of multiple stressors associated with work and work
      environment, and other personal factors. ANOVA indicated that the perception of
      work aspects as stressors differed significantly between male and female workers.

PMID- 24934432
TI  - Vision for improvement: Expressive writing as an intervention for people with
      Stargardt's disease, a rare eye disease.
AB  - This study implemented and evaluated the effectiveness of an expressive writing
      intervention among patients with Stargardt's disease, a rare disease due to
      macular degeneration. Participants were randomly assigned to either an expressive
      writing intervention or a neutral writing condition. Participants completed
      measures at three time points: baseline, 3 weeks, and 6 weeks post-intervention.
      Psychological health outcomes improved at the 3-week follow-up for the
      intervention condition compared to control. Self-reported physical health
      improved at the 6-week follow-up in the intervention condition compared to
      control. These results suggest that expressive writing may be an effective,
      practical, and low-cost intervention for those with Stargardt's disease.

PMID- 24934433
TI  - Type D personality is associated with health behaviors and perceived social
      support in individuals with coronary heart disease.
AB  - This study investigated the role of Type D personality in health behaviors and
      perceived social support in individuals with coronary heart disease. Different
      from other related studies, this study assessed a broader range of health
      behaviors in an eastern population while controlling for anxiety and depression.
      In all, 386 Indonesian individuals with coronary heart disease completed the
      measures assessing Type D, perceived social support, depression, anxiety, and
      health behaviors. Compared with non-Type D, Type D individuals reported more
      unhealthy behaviors, less healthy behaviors, and perceived less social support.
      For those identified as Type D, tailored interventions might be considered.

PMID- 24934434
TI  - Emotional representation of tuberculosis with stigma, treatment delay, and
      medication adherence in Russia.
AB  - This descriptive cross-sectional study aimed to explore emotional representation
      and illness coherence, the understanding a person has about an illness which
      helps them make sense of the experience, in Russians with tuberculosis. In a
      secondary analysis of questionnaires from 105 Russians treated for pulmonary
      tuberculosis, social isolation and disease consequences were predictors of
      negative emotions related to tuberculosis and accounted for 49 percent of the
      variance. Participants who scored higher on illness coherence were less likely to
      experience negative emotions. Development of programs to help patients understand
      tuberculosis and to manage emotional responses and stigma is suggested.

PMID- 24934435
TI  - Bodies as means for continuing post-death relationships.
AB  - Secondary analysis of data from 30 people in three interview studies shows that
      bereaved people use their own and the deceased's body in their continuing efforts
      to maintain a relationship with the departed. Following the continuing bond
      perspective, the study reveals three body-associated strategies for maintaining
      post-death relationships: (a) the presence of the deceased in the bereaved's
      body, (b) body-associated actions and activities, and (c) sensing and caring for
      the deceased's body. The conceptual dimension of embodiment is used to interpret
      results. Attention is also given to the bereaved's sense of disembodiment due to
      social rejection of these strategies for maintaining post-death relationships.
      Implications for health psychologists are offered.

PMID- 24934436
TI  - Clinicians' perspectives on patient satisfaction in adult congenital heart
      disease clinics--a dimension of health care quality whose time has come.
AB  - OBJECTIVES: Patient-centered care and patient satisfaction represent key
      dimensions of health care quality. This is relevant for the growing number of
      patients with life-long conditions. In the present study, our goal was to examine
      clinicians' attitudes and behavior with respect to patient satisfaction in adult
      congenital heart disease outpatient clinics. METHODS: A 34-question survey was
      developed to assess adult congenital heart disease clinicians' awareness,
      attitudes, and behavior relative to patient satisfaction and administered in
      person or online to clinicians from the largely U.S.-based Adult Congenital Heart
      Association's database of adult congenital heart disease health care providers.
      RESULTS: Overall, 267 questionnaires were filled out: 108 were collected in
      person (79% response rate) and 159 online (17.5% response rate). Responses were
      received from physicians (161); nurses (73); physician assistants (20); and
      others (13). Although 85% of clinicians believed it was important to inquire
      about patient satisfaction, only 28% reported routinely inquiring about this
      dimension of care. Only 34% claimed they had adequate training to cope with
      varying levels of patient satisfaction, 44% stated that their department utilized
      patient satisfaction surveys, and 37% received feedback from the hospital
      management in the preceding 12 months. In multivariate analyses, clinicians that
      received feedback from the hospital management and had adequate training were
      more likely to inquire about patient satisfaction. CONCLUSION: Although patient
      satisfaction is perceived as an important dimension of quality care by adult
      congenital heart disease clinicians, most of them reported insufficient
      institutional support to achieve this. Our findings suggest that clinicians would
      benefit from health care organizations engaging them in the delivery of this
      dimension of health care quality.

PMID- 24934437
TI  - Exchange interaction between magnetic impurities on surfaces of Cu(x)Pd(1-x) and
      Cu(x)Au(1-x) random substitutional alloys.
AB  - We present fully relativistic first principles calculations of the exchange
      interactions between magnetic impurities deposited on the (1 1 1) surfaces of
      CuxPd1-x and CuxAu1-x random substitutional alloys, described using the coherent
      potential approximation. We show that as with pure surfaces of Cu and Au, where
      Shockley-type surface states mediate an RKKY-type interaction, a surface state
      and its dispersion can be obtained from studying the Bloch spectral function. In
      the second part of the paper we show how the details of the interaction are
      determined by the properties and dispersion of the surface states of the host
      material. We find an extra exponential decay in the range of the interactions
      compared to the 1/R(2) decay on surfaces of pure metals. The similar topology of
      the Fermi surface of Cu and Au allows us to scale the spin-orbit coupling and to
      study the Bychkov-Rashba splitting. Alternatively, the entirely different
      topology of the Cu and Pd Fermi surfaces allows us to study changes in the
      surface-state dispersion of the RKKY interaction between surface impurities. 

PMID- 24934438
TI  - Maternal microcirculation and sidestream dark field imaging: a prospective
      assessment of the association between labour pain and analgesia on the
      microcirculation of pregnant women.
AB  - BACKGROUND: Pregnancy places significant demands on the cardiovascular system
      leading to measurable changes in the macrocirculation and potentially the
      microcirculation. During labour, both uterine contractions and labour pain can
      further impact cardiovascular status. The objective of this observational study
      was to compare sublingual microcirculation in labouring parturients before and
      after epidural analgesia. METHODS: Healthy pregnant, labouring women requesting
      epidural analgesia were approached to participate. Participants with
      cardiovascular disease, diabetes, obesity, smoking or caffeine intake were
      excluded. The sidestream dark field device was applied to the sublingual mucosa
      obtaining images of at least 20 seconds in 5 visual fields before and after
      epidural analgesia. Video clips were analyzed randomly and blindly. The primary
      outcome was mean microvascular flow index (MFI). RESULTS: Twelve participants
      completed this study. The results demonstrate no statistically significant
      difference in the MFI during labour pain (2.9+/-0.1) compared to after epidural
      analgesia (3.0+/-0.04, p = 0.31). Furthermore, there were no statistically
      significant differences in any secondary outcomes. CONCLUSION: Our findings
      indicate that epidural analgesia may not impact sublingual microcirculation in
      labouring women. This agrees with literature supporting epidural analgesia as a
      safe, appropriate method of pain relief during labour with limited impact on
      peripheral macro or microcirculation.

PMID- 24934439
TI  - Nitrogen and phosphorus losses from agricultural systems in China: a meta
      analysis.
AB  - Studies worldwide have indicated that agricultural pollution is the main source
      of nitrogen and phosphorus (N and P) in surface waters. A systematic
      understanding of N and P sources and sinks in agricultural systems is important
      for selecting the appropriate remedial strategies to control nutrient losses and
      water pollution. Based on nationwide data and a long-term monitoring program in
      Southeast China, the nationwide spatial and temporal patterns of N and P losses
      and the relationships between such losses and N and P inputs and rainfall were
      analyzed. The results showed that the annual nutrient losses from agricultural
      systems in China strongly varied, and the N/P values ranged from 0.01 to 51.0,
      with a majority at approximately 0-20, and an arithmetic mean of 9.73; these
      values mostly overlap the suitable range of N/P (6-15) for red bloom algae. 

PMID- 24934441
TI  - Oil spill hazard assessment using a reverse trajectory method for the Egadi
      marine protected area (Central Mediterranean Sea).
AB  - The Egadi Marine Protected Area (MPA) on the western side of the Sicily Channel
      (Central Mediterranean) is exposed to a high risk of oil pollution from the
      tanker routes connecting the eastern and western basins of the Mediterranean Sea.
      Areas where an oil spill would do most damage, and thus where surveillance should
      be concentrated, are identified in this study by Lagrangian tracers tracked
      backwards in time from points along the MPA perimeter using data spanning six
      years from 2006 to 2011. Results indicate that the areas where oil surveillance
      would be most beneficial are segments of the tanker routes south of Sicily
      (highly frequented) and north of Sicily (scarcely frequented), both extending
      about 150 miles from November to March and 100 miles in the other months. The
      third route, close to the Tunisian shore, is the most frequented by oil tankers
      but the threat period is limited to November and December. 

PMID- 24934440
TI  - Contamination of diuron in coastal waters around Malaysian Peninsular.
AB  - The use of antifouling paints to the boats and ships is one among the threats
      facing coastal resources including coral reefs in recent decades. This study
      reports the current contamination status of diuron and its behaviour in the
      coastal waters of Malaysia. The maximum concentration of diuron was 285 ng/L
      detected at Johor port. All samples from Redang and Bidong coral reef islands
      were contaminated with diuron. Temporal variation showed relatively high
      concentrations but no significant difference (P>0.05) during November and January
      (North-East monsoon) in Klang ports (North, South and West), while higher levels
      of diuron were detected during April, 2012 (Inter monsoon) in Kemaman, and Johor
      port. Although no site has shown concentration above maximum permissible
      concentration (430 ng/L) as restricted by the Dutch Authorities, however, long
      term exposure studies for environmental relevance levels of diuron around coastal
      areas should be given a priority in the future.

PMID- 24934444
TI  - Characterization of Barmah Forest virus pathogenesis in a mouse model.
AB  - Alphaviruses including Barmah Forest virus (BFV) and Ross River virus (RRV) cause
      arthritis, arthralgia and myalgia in humans. The rheumatic symptoms in human BFV
      infection are very similar to those of RRV. Although RRV disease has been studied
      extensively, little is known about the pathogenesis of BFV infection. We sought
      to establish a mouse model for BFV to facilitate our understanding of BFV
      infectivity, tropism and pathogenesis, and to identify key pathological and
      immunological mechanisms of BFV infection that may distinguish between infections
      with BFV and RRV. Here, to the best of our knowledge, we report the first study
      assessing the virulence and replication of several BFV isolates in a mouse model.
      We infected newborn Swiss outbred mice with BFV and established that the BFV2193
      prototype was the most virulent strain. BFV2193 infection resulted in the highest
      mortality among all BFV variant isolates, comparable to that of RRV. In
      comparison with RRV, C57BL/6 mice infected with BFV showed delayed onset,
      moderate disease scores and early recovery of the disease. BFV replicated poorly
      in muscle and did not cause the severe myositis seen in RRV-infected mice. The
      mRNAs for the inflammatory mediators TNF-alpha, IL-6, CCL2 and arginase-1 were
      highly upregulated in RRV- but not BFV-infected muscle. To our knowledge, this is
      the first report of a mouse model of BFV infection, which we have used to
      demonstrate differences between BFV and RRV infections and to further understand
      disease pathogenesis. With an increasing number of BFV cases occurring annually,
      a better understanding of the disease mechanisms is essential for future
      therapeutic development. 

PMID- 24934443
TI  - Human muscle LIM protein dimerizes along the actin cytoskeleton and cross-links
      actin filaments.
AB  - The muscle LIM protein (MLP) is a nucleocytoplasmic shuttling protein playing
      important roles in the regulation of myocyte remodeling and adaptation to
      hypertrophic stimuli. Missense mutations in human MLP or its ablation in
      transgenic mice promotes cardiomyopathy and heart failure. The exact function(s)
      of MLP in the cytoplasmic compartment and the underlying molecular mechanisms
      remain largely unknown. Here, we provide evidence that MLP autonomously binds to,
      stabilizes, and bundles actin filaments (AFs) independently of calcium and pH.
      Using total internal reflection fluorescence microscopy, we have shown how MLP
      cross-links actin filaments into both unipolar and mixed-polarity bundles.
      Quantitative analysis of the actin cytoskeleton configuration confirmed that MLP
      substantially promotes actin bundling in live myoblasts. In addition, bimolecular
      fluorescence complementation (BiFC) assays revealed MLP self-association.
      Remarkably, BiFC complexes mostly localize along actin filament-rich structures,
      such as stress fibers and sarcomeres, supporting a functional link between MLP
      self-association and actin cross-linking. Finally, we have demonstrated that MLP
      self-associates through its N-terminal LIM domain, whereas it binds to AFs
      through its C-terminal LIM domain. Together our data support that MLP contributes
      to the maintenance of cardiomyocyte cytoarchitecture by a mechanism involving its
      self-association and actin filament cross-linking. 

PMID- 24934445
TI  - CD1d-restricted antigen presentation by Vgamma9Vdelta2-T cells requires
      trogocytosis.
AB  - CD1d-restricted invariant natural killer T cells (iNKT) constitute an important
      immunoregulatory T-cell subset that can be activated by the synthetic glycolipid
      alpha-galactosylceramide (alpha-GalCer) and play a dominant role in antitumor
      immunity. Clinical trials with alpha-GalCer-pulsed monocyte-derived dendritic
      cells (moDC) have shown anecdotal antitumor activity in advanced cancer. It was
      reported that phosphoantigen (pAg)-activated Vgamma9Vdelta2-T cells can acquire
      characteristics of professional antigen-presenting cells (APC). Considering the
      clinical immunotherapeutic applications, Vgamma9Vdelta2-T APC can offer important
      advantages over moDC, potentially constituting an attractive novel APC platform.
      Here, we demonstrate that Vgamma9Vdelta2-T APC can present antigens to iNKT.
      However, this does not result from de novo synthesis of CD1d by Vgamma9Vdelta2-T,
      but critically depends on trogocytosis of CD1d-containing membrane fragments from
      pAg-expressing cells. CD1d-expressing Vgamma9Vdelta2-T cells were able to
      activate iNKT in a CD1d-restricted and alpha-GalCer-dependent fashion. Although
      alpha-GalCer-loaded moDC outperformed Vgamma9Vdelta2-T APC on a per cell basis,
      Vgamma9Vdelta2-T APC possess unique features with respect to clinical
      immunotherapeutic application that make them an interesting platform for
      consideration in future clinical trials.

PMID- 24934442
TI  - The E2F transcription factors regulate tumor development and metastasis in a
      mouse model of metastatic breast cancer.
AB  - While the E2F transcription factors (E2Fs) have a clearly defined role in cell
      cycle control, recent work has uncovered new functions. Using genomic signature
      methods, we predicted a role for the activator E2F transcription factors in the
      mouse mammary tumor virus (MMTV)-polyomavirus middle T oncoprotein (PyMT) mouse
      model of metastatic breast cancer. To genetically test the hypothesis that the
      E2Fs function to regulate tumor development and metastasis, we interbred MMTV
      PyMT mice with E2F1, E2F2, or E2F3 knockout mice. With the ablation of individual
      E2Fs, we noted alterations of tumor latency, histology, and vasculature.
      Interestingly, we noted striking reductions in metastatic capacity and in the
      number of circulating tumor cells in both the E2F1 and E2F2 knockout backgrounds.
      Investigating E2F target genes that mediate metastasis, we found that E2F loss
      led to decreased levels of vascular endothelial growth factor (Vegfa), Bmp4,
      Cyr61, Nupr1, Plod 2, P4ha1, Adamts1, Lgals3, and Angpt2. These gene expression
      changes indicate that the E2Fs control the expression of genes critical to
      angiogenesis, the remodeling of the extracellular matrix, tumor cell survival,
      and tumor cell interactions with vascular endothelial cells that facilitate
      metastasis to the lungs. Taken together, these results reveal that the E2F
      transcription factors play key roles in mediating tumor development and
      metastasis in addition to their well-characterized roles in cell cycle control. 

PMID- 24934446
TI  - Prostate cancer: viral gene therapy can improve IMRT.

PMID- 24934448
TI  - Prostate cancer: extended pelvic lymph node removal--extended survival.

PMID- 24934449
TI  - Prostate cancer: enzalutamide PREVAILs.

PMID- 24934447
TI  - Mechanisms of testicular torsion and potential protective agents.
AB  - Testicular torsion is a urological emergency most commonly seen in adolescence,
      involving a decrease in blood flow in the testis resulting from torsion of the
      spermatic cord that can result in gonad injury or even loss if not treated in
      time. Testicular ischaemia-reperfusion injury represents the principle
      pathophysiology of testicular torsion, with ischaemia caused by twisting of the
      spermatic cord, and reperfusion on its subsequent release. Many cellular and
      molecular mechanisms are involved in ischaemia-reperfusion injury following
      testicular torsion. Studies have investigated the use of pharmacological agents
      as supportive therapy to surgical repair in order to prevent the adverse effects
      of testicular torsion. Numerous substances have been proposed as important in the
      prevention of post-ischaemia-reperfusion testicular injury. A range of chemicals
      and drugs has been successfully tested in animal models for the purpose of
      mitigating the dangerous effects of ischaemia-reperfusion in testis torsion. 

PMID- 24934450
TI  - Diagnosis and management of intradiverticular bladder tumours.
AB  - Intradiverticular bladder tumours (IDBT) account for approximately 1% of all
      urinary bladder tumours. The risk of developing a tumour within a bladder
      diverticulum is considered to be greater than in the main bladder, possibly owing
      to prolonged contact of potential carcinogens with the mucosal lining from
      urinary stasis. Patients with these tumours most commonly present with visible
      haematuria. Diagnostic tests include urine cytology, cystoscopy, ultrasonography,
      CT, MRI, and biopsy. Lack of muscle in the diverticula increases the risk of
      bladder perforation during biopsy and makes pathological staging difficult as
      there is no T2 stage; instead, data suggest that any invasion beyond the lamina
      propria should be described as T3. IDBT can be managed by transurethral resection
      and adjuvant intravesical therapy, diverticulectomy, or cystectomy (partial or
      radical), as outlined by the only guidelines to specifically address the
      management of IDBT, which were published by the Cancer Committee of the French
      Association of Urology (CCAFU) in 2012. The prognosis of patients with
      intradiverticular bladder tumours has always been perceived to be worse than
      those with intravesical tumours; however, the only study of 5-year survival rates
      for patients with IDBT suggests that prognosis might be comparable for these
      conditions. 

PMID- 24934451
TI  - Fetal therapy for the treatment of congenital bladder neck obstruction.
AB  - Lower urinary tract obstruction (LUTO) comprises a heterogeneous group of
      pathologies associated with early-onset oligohydramnios and cystic renal disease
      that have high rates of perinatal morbidity (from renal disease) and mortality
      (from pulmonary hypoplasia). The use of prenatal detailed ultrasonography and
      fetal urine analysis has been only partially successful in identifying fetuses
      with LUTO with relatively good prognosis that would benefit from in utero
      therapy. The most common prenatal therapy is vesicoamniotic shunting. Newer
      techniques, such as fetal cystoscopy, have potential for enhancing prenatal
      triage and simultaneously delivering treatment. Vesicoamniotic shunting seems to
      improve perinatal survival, but whether this treatment or conservative management
      is used, the surviving children have a high rate of end-stage renal failure
      requiring dialysis and transplantation. Further investigation of long-term
      outcomes of vesicoamniotic shunting and fetal cystoscopy is hoped to delineate
      the risks and benefits of these prenatal treatments and inform management
      strategies.

PMID- 24934453
TI  - Functions of invariant NK T cells are modulated by TLR ligands and IFN-alpha.
AB  - Invariant NK T (iNKT) cells perform numerous immunoregulatory functions. In mice,
      they express a unique and invariant Valpha14-Jalpha18 rearrangement of alpha
      chain in their TCR recognizing glycolipid Ags presented by CD1d. This recognition
      results in the rapid release of both Th1- and Th2-type cytokines, making them
      early mediators of the immune response. Owing to their rapid activation and
      genetic rigidity of their TCR, iNKT cells share characteristics with innate
      lymphocytes. Therefore, we investigated whether iNKT cells could be induced to
      express TLRs, a class of pathogen recognition receptor. Mouse iNKT cells were
      stimulated with anti-CD3 monoclonal Ab and IFN-alpha, resulting in an increase in
      the transcription of TLRs 3, 5, 7 and 9, and increased surface expression of
      TLR3. These cells were subsequently stimulated with TLR ligands, resulting in an
      increase in the production of IFN-gamma, IL-4 and TNF-alpha. Supernatants from
      these cells also increased macrophage production of IL-6 and prostaglandin E2,
      and increased their phagocytic activity and CD80 expression. These supernatants
      also reduced vesicular stomatitis virus-GFP replication in fibroblasts. This
      study demonstrates the role of IFN-alpha in iNKT cell activation, as well as the
      direct modulatory effects of TLR ligands on iNKT cell function, including
      antiviral activity. 

PMID- 24934452
TI  - The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM)
      Foundation model.
AB  - Knowledge contained within in vivo imaging annotated by human experts or computer
      programs is typically stored as unstructured text and separated from other
      associated information. The National Cancer Informatics Program (NCIP) Annotation
      and Image Markup (AIM) Foundation information model is an evolution of the
      National Institute of Health's (NIH) National Cancer Institute's (NCI) Cancer
      Bioinformatics Grid (caBIG(r)) AIM model. The model applies to various image
      types created by various techniques and disciplines. It has evolved in response
      to the feedback and changing demands from the imaging community at NCI. The
      foundation model serves as a base for other imaging disciplines that want to
      extend the type of information the model collects. The model captures physical
      entities and their characteristics, imaging observation entities and their
      characteristics, markups (two- and three-dimensional), AIM statements,
      calculations, image source, inferences, annotation role, task context or
      workflow, audit trail, AIM creator details, equipment used to create AIM
      instances, subject demographics, and adjudication observations. An AIM instance
      can be stored as a Digital Imaging and Communications in Medicine (DICOM)
      structured reporting (SR) object or Extensible Markup Language (XML) document for
      further processing and analysis. An AIM instance consists of one or more
      annotations and associated markups of a single finding along with other ancillary
      information in the AIM model. An annotation describes information about the
      meaning of pixel data in an image. A markup is a graphical drawing placed on the
      image that depicts a region of interest. This paper describes fundamental AIM
      concepts and how to use and extend AIM for various imaging disciplines. 

PMID- 24934454
TI  - Partner's engagement in community-based health promotion programs: a case study
      of professional partner's experiences and perspectives in Iran.
AB  - Community-based health promotion requires effective participation and partnership
      of diverse and numerous stakeholders from community as well as external
      professional organizations. Although effective partnership of stakeholders is
      often the key for success of health promotion practice and research, but this has
      proved to be a complex and challenging task. This study is an exploratory study
      to identify professional stakeholder's perspectives and experiences toward the
      partner's engagement challenges in community-based participatory research
      conducted in Population Research Centers in Iran. A qualitative study design with
      in-depth semi-structured interviews as data collection method was chosen. Using
      purposeful sampling technique, policy-makers and managers (mainly academics)
      involved in community-based participatory research in these centers were invited
      to be interviewed. Data were collected to the point where no new information was
      forthcoming. All interviews were taped and transcribed. To provide answers for
      research questions, qualitative content analysis was employed to extract emerging
      main themes from numerous cods. Findings were categorized in three main themes as
      Partnership's relationship and trust issues, Partnership's individual issues and
      Partnership's system issues. Although community-based participatory research in
      Iran benefits from more than a decade history and some physical infrastructures,
      but it seems that public health experts and researchers and other partner
      organizations are lagging behind in terms of capacities and competencies required
      to effectively utilize the available structure and opportunities. Hence, capacity
      development, both among professional partners and community may be the main way
      forward to tackling the future challenges for strengthening community actions but
      should include both levels of individuals and systems. 

PMID- 24934455
TI  - Examining the quality of the 'Healthy Eating and Physical Activity in Schools'
      (HEPS) quality checklist: German results on usability and reliability.
AB  - The aim of the present study was to examine the usability and reliability of the
      HEPS quality checklist (Healthy Eating and Physical Activity in Schools), an
      instrument developed to assess the quality of school-based programmes on healthy
      eating and physical activity. With regard to usability, health promotion experts
      (n = 15) were asked to apply the HEPS quality checklist and to fill out a
      questionnaire about its comprehensibility and usability. To examine inter-rater
      reliability (IRR) a criteria-based selection of German school programmes on
      healthy eating and physical activity (n = 14) was randomly allocated to two
      programme pools and assessed independently by the authors. Results of the pilot
      testing revealed a high overall satisfaction with the HEPS quality checklist and
      a high willingness to use it or to recommend it to others. Furthermore, the
      checklist was perceived to be comprehensive and clearly structured. The
      assessment results of programme pool 1 revealed unsatisfactory Cohen's Kappa
      coefficients (IRR) and moderate intra-class correlations (ICC). After the HEPS
      manual guide had been amended with regard to its anchoring, the results of
      programme pool 2 showed substantial improvements with regard to IRR and ICC. In
      summary, the adapted HEPS quality checklist is a usable and reliable instrument
      for the quality assessment of school-based programmes on healthy eating and
      physical activity. The findings suggest that the HEPS checklist should be applied
      by two sufficiently trained raters. 

PMID- 24934456
TI  - Development of hydrophilic nanocarriers for the charged form of the local
      anesthetic articaine.
AB  - One of the current challenges in drug encapsulation concerns the development of
      carrier systems for hydrophilic compounds. Potential carriers include
      nanocapsules prepared with amphiphilic polymers, which consist of a polymeric
      coating surrounding an aqueous nucleus, or dense matrices such as nanospheres of
      alginate/chitosan, where the drug may be dispersed in the matrix or adsorbed on
      the surface. The development of new formulations of nanocarriers, for example the
      poly(ethylene glycol)-poly(E-caprolactone) (PEG-PCL) nanocapsules and
      alginate/chitosan (AG/CS) nanospheres described in this work, is needed in the
      case of ionized drugs such as articaine. This amino amide local anesthetic is the
      drug of choice in dentistry for regional anesthesia as well as the relief of
      acute and chronic pain. Here, the physico-chemical properties of suspensions of
      the nanoparticles (considering diameter, polydispersion, and zeta potential) were
      determined as a function of time, in order to establish the stability of the
      systems. The formulations did not show any substantial changes in these
      parameters, and were stable for up to 120 days of storage at ambient temperature.
      Satisfactory encapsulation efficiencies were obtained for the PEG-PCL
      nanocapsules (60%) and the AG/CS nanospheres (45%). Cytotoxicity assays confirmed
      that the encapsulation of articaine reduced its toxicity, relative to the free
      drug. The most promising results were obtained using the vesicular system (PEG
      PCL nanocapsules), which not only altered the release profile of the drug, but
      also resulted in the lowest toxicity. This carrier system therefore holds promise
      for use in future practical applications. 

PMID- 24934457
TI  - Bone health in patients with prostate cancer.
AB  - CONTEXT: In patients with prostate cancer, bone health is compromised by advanced
      age at diagnosis, androgen suppression treatments and the developmentofbone
      metastases. In this paper the medical literature is reviewed in order to update
      the state of the art on their incidence, prevention and management. EVIDENCE
      ACQUISITION: A literature review about bone involvement in patients with prostate
      cancer in different clinical settings is performed. SYNTHESIS OF THE EVIDENCE:
      Decreased bone mineral density is higher in patients diagnosed of prostate cancer
      before starting treatment than in healthy men with the same age. During the first
      year of treatment, a severe loss bone density is reported due to androgen
      suppression therapy. From then on, loss bone density seems to slow down,
      persisting at long-term. It is important to know the starting point and the
      dynamics of loss bone in order to prevent its progression. The skeletal events
      have an important impact on quality of life in patients with prostate cancer.
      Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone.
      CONCLUSIONS: The prevention and management of bone involvement in patients with
      prostate cancer is critical to quality of life in these patients and requires an
      individualized approach. Before starting a prolonged androgen deprivation,
      baseline risk of fracture should be evaluated in order to adopt the proper
      protective measures. In patients with metastases, early treatments reducing the
      risk of bone events should be taken into account.

PMID- 24934458
TI  - Comparative study of retrograde intrarenal surgery and micropercutaneous
      nephrolithotomy in the treatment of intermediate-sized kidney stones.
AB  - OBJECTIVE: Retrograde intrarenal surgery (RIRS) has proven efficacy with minimal
      morbidity in the treatment of intermediate-sized kidney stones. The aim of this
      study was to examine the feasibility of micropercutaneous nephrolithotomy
      (microperc) for this indication and evaluate its results compared with those of
      RIRS. MATERIAL AND METHODS: From September to December 2013, we performed a
      comparative prospective study between RIRS and microperc, with 20 consecutive
      patients with intermediate-sized (1-3cm) kidney stones. We employed a flexible
      dual-channel ureteroscope (Cobra, Richard Wolf GmbH) and a Microperc 4.85/8 Fr
      (with the patient supine) with flexible fiberoptics (0.9mm, 120 degrees  and
      10,000 pixels) (PolyDiagnost GmbH). The study variables were demographic data,
      stone characteristics, percentage of stone elimination, complications (Clavien
      Dindo), surgical time, hospital stay and need for auxiliary procedures. RESULTS:
      The patients underwent RIRS (n=12) or microperc (n=8). There were no differences
      in the demographics or stone characteristics between the 2 groups. The percentage
      of stone elimination with RIRS and microperc was 91.7% and 87.5% (P=1),
      respectively. One of the patients who underwent RIRS (8.3%) experienced
      postoperative fever; one of the patients who underwent microperc (12.5%)
      experienced postoperative colic pain (both cases were classified as Clavien I).
      The operative times were similar: 120min (111.2-148.7) and 120 (88.7-167.5) min
      for RIRS and microperc (P=.8), respectively. None of the patients required a
      blood transfusion. The hospital stays were also equivalent: 1 day (1-2) and 1.5
      days (1-3.5) for RIRS and microperc (P=.33), respectively. Two patients treated
      with microperc (25%) required auxiliary procedures (simultaneous RIRS and
      flexible nephroscopy after percutaneous trajectory dilation to treat, in both
      cases, a significant fragment that had migrated to an inaccessible calyx), and 1
      patient in the RIRS group (8.3%) required percutaneous nephrolithotomy due to
      unfavorable infundibular-calyceal anatomy (P=.54). CONCLUSIONS: Microperc is a
      minimally invasive method that is emerging as an effective and safe treatment for
      intermediate-sized kidney stones. Studies are needed to better evaluate its cost
      effectiveness, the need for complementary treatments and its possible
      complementarity with RIRS when working with patients in the supine position.

PMID- 24934459
TI  - Safety and efficacy even after 90 years of age should prompt removal of upper age
      limits in systemic thrombolysis for stroke.

PMID- 24934460
TI  - Thrombolysis in the elderly: yes but with caution.

PMID- 24934463
TI  - Vasa vasorum in normal and diseased arteries.

PMID- 24934465
TI  - ECG Response: June 17, 2014.

PMID- 24934464
TI  - Glycemic management in patients with coronary artery disease and prediabetes or
      type 2 diabetes mellitus.

PMID- 24934466
TI  - Left atrial appendage occluder thrombosis after successful implantation.

PMID- 24934467
TI  - Left anterior descending coronary artery occlusion secondary to metastatic
      squamous cell carcinoma presenting as ST-segment-elevation myocardial infarction.

PMID- 24934468
TI  - Letter by Scharnagl et al regarding article, "Elevated remnant cholesterol causes
      both low-grade inflammation and ischemic heart disease, whereas elevated low
      density lipoprotein cholesterol causes ischemic heart disease without
      inflammation".

PMID- 24934469
TI  - Letter by Jones et al regarding article, "Elevated remnant cholesterol causes
      both low-grade inflammation and ischemic heart disease, whereas elevated low
      density lipoprotein cholesterol causes ischemic heart disease without
      inflammation".

PMID- 24934470
TI  - Reply to letters regarding article, "Elevated remnant cholesterol causes both low
      grade inflammation and ischemic heart disease, whereas elevated low-density
      lipoprotein cholesterol causes ischemic heart disease without inflammation".

PMID- 24934471
TI  - DSM-5 and the rise of the diagnostic checklist.

PMID- 24934472
TI  - A broad survey reveals substitution tolerance of residues ligating FeS clusters
      in [NiFe] hydrogenase.
AB  - BACKGROUND: In order to understand the effects of FeS cluster attachment in
      [NiFe] hydrogenase, we undertook a study to substitute all 12 amino acid
      positions normally ligating the three FeS clusters in the hydrogenase small
      subunit. Using the hydrogenase from Alteromonas macleodii "deep ecotype" as a
      model, we substituted one of four amino acids (Asp, His, Asn, Gln) at each of the
      12 ligating positions because these amino acids are alternative coordinating
      residues in otherwise conserved-cysteine positions found in a broad survey of
      NiFe hydrogenase sequences. We also hoped to discover an enzyme with elevated
      hydrogen evolution activity relative to a previously reported "G1" (H230C/P285C)
      improved enzyme in which the medial FeS cluster Pro and the distal FeS cluster
      His were each substituted for Cys. RESULTS: Among all the substitutions screened,
      aspartic acid substitutions were generally well-tolerated, and examination
      suggests that the observed deficiency in enzyme activity may be largely due to
      misprocessing of the small subunit of the enzyme. Alignment of hydrogenase
      sequences from sequence databases revealed many rare substitutions; the five
      substitutions present in databases that we tested all exhibited measurable
      hydrogen evolution activity. Select substitutions were purified and tested,
      supporting the results of the screening assay. Analysis of these results confirms
      the importance of small subunit processing. Normalizing activity to quantity of
      mature small subunit, indicative of total enzyme maturation, weakly suggests an
      improvement over the "G1" enzyme. CONCLUSIONS: We have comprehensively screened
      48 amino acid substitutions of the hydrogenase from A. macleodii "deep ecotype",
      to understand non-canonical ligations of amino acids to FeS clusters and to
      improve hydrogen evolution activity of this class of hydrogenase. Our studies
      show that non-canonical ligations can be functional and also suggests a new
      limiting factor in the production of active enzyme.

PMID- 24934473
TI  - In vitro investigation of antioxidant, anti-Inflammatory, and antiplatelet
      adhesion properties of genistein-modified
      poly(ethersulfone)/poly(vinylpyrrolidone) hemodialysis membranes.
AB  - Hemocompatibility of genistein-modified poly(ethersulfone)/poly(vinylpyrrolidone)
      (PES/PVP) hemodialysis (HD) membranes has been investigated in vitro with
      emphasis on evaluation of cell viability, antioxidant, anti-inflammatory, and
      antiplatelet adhesion properties. Genistein modified PES/PVP membranes reveal
      significant reduction of the reactive oxygen species and also considerable
      suppression of interleukin-1beta and tumor necrosis factor-alpha levels in whole
      blood, but to a lesser extent ininterleukin-6. The incorporation of PVP into the
      HD membrane reduces platelet adhesion by virtue of its hydrophilicity. Of
      particular importance is that platelet adhesion of the genistein modified
      membranes declines noticeably at low concentrations of genistein for about 5-10%,
      beyond which it raises the number of adhered platelets. The initial decline in
      the platelet adhesion is attributable to genistein's ability to inhibit
      intercellular and/or vascular cell adhesion, whereas the reversal of this
      adhesion trend with further increase of genistein loading is ascribed to the
      inherent hydrophobicity of the genistein modified HD membrane.

PMID- 24934474
TI  - Ketamine-related cholangiopathy: a retrospective study on clinical and imaging
      findings.
AB  - PURPOSE: Ketamine is a commonly abused recreational drug in Southeast Asia. There
      are emerging reports on ketamine abuse causing liver injury and biliary
      dilatation. This retrospective study aims to investigate the clinical and
      radiological features of this condition. METHODS: A retrospective search in the
      database of our institute was performed from January 2008 to February 2014 for
      patients who were ketamine abusers, with deranged liver function and/or
      epigastric pain, and had computed tomography of the abdomen or magnetic resonance
      cholangiopancreatography. Patient demographics, clinical data, and radiological
      findings were reviewed. RESULTS: Twenty-six patients (11 male and 15 female) were
      included in this study. Eighteen (69 %) patients had fusiform dilatation of the
      common bile ducts (CBDs) without evidence of intrinsic or extrinsic obstruction,
      and non-dilated intrahepatic ducts. The degree of CBD dilatation correlated with
      duration of abuse. In five patients who achieved abstinence, the CBD dilatation
      showed improvement. CONCLUSIONS: Ketamine-related cholangiopathy manifested as
      fusiform dilatation of the CBD without evidence of obstructive lesions. Severity
      of CBD dilatation appears to be correlated with the duration of ketamine, and the
      condition is potentially reversible in abstinent patients.

PMID- 24934475
TI  - Heterotopic pancreas of the jejunum: associations between CT and pathology
      features.
AB  - PURPOSE: To investigate the computed tomography (CT) features of heterotopic
      pancreas of the jejunum (HPJ) and to assess their associations with HPJ pathology
      features. METHODS: In this retrospective series analysis, two radiologists
      reviewed the CT images of 17 patients with surgically proven HPJ in order to
      determine in consensus the location, long diameter, margin, shape, contour, and
      growth pattern of the lesions, the presence of a duct-like structure, the lesion
      enhancement patterns, including the homogeneity, and the degree of contrast
      enhancement compared with that of the main pancreas. The pathology features of
      the surgical specimens were reviewed and their associations with the CT features
      were assessed. RESULTS: On CT, the HPJs typically appeared as a small (<3 cm),
      well-defined, ovoid or flat-shaped mass in the proximal jejunum with multiple and
      tiny lobulations. The growth pattern varied and the duct-like structure was
      rarely visible. The HPJs mostly appeared to be homogeneous and exhibited hyper-
      or isoattenuation compared to the main pancreas in the arterial and portal
      phases. However, these enhancement patterns varied slightly depending on the
      microscopic composition of the lesions (i.e., acinar vs. ductal predominance).
      Most HPJs comprised histologically of large acini, some ducts, and small islet
      cells, and had ductal communication with the jejunum. CONCLUSIONS: HPJs typically
      manifested as small, well-defined, ovoid or flat-shaped, homogeneous, and well
      enhancing masses with a microlobulated contour in the proximal jejunum on CT, and
      their enhancement patterns associated with their microscopic composition. The
      pathology features of HPJs generally mimic those of the normal pancreas.

PMID- 24934476
TI  - Erratum to: ACR appropriateness criteria((r)) imaging of mesenteric ischemia.

PMID- 24934477
TI  - Recent developments in anion induced capsular self-assemblies.
AB  - This Feature Article covers recent developments in anion induced capsular self
      assemblies, with particular focus on important reports from 2011 to 2013.
      Contemporary studies on the capsular binding of environmentally and biologically
      relevant anions in aqueous medium are described. Emerging reports of such systems
      reveal their potential utility towards various functional aspects like anion
      separation, CO2 fixation, hydrated halide recognition and anion transportation.
      This article also highlights potential applications of anion induced molecular
      capsules. 

PMID- 24934478
TI  - Lamb-Dicke spectroscopy of atoms in a hollow-core photonic crystal fibre.
AB  - Unlike photons, which are conveniently handled by mirrors and optical fibres
      without loss of coherence, atoms lose their coherence via atom-atom and atom-wall
      interactions. This decoherence of atoms deteriorates the performance of atomic
      clocks and magnetometers, and also hinders their miniaturization. Here we report
      a novel platform for precision spectroscopy. Ultracold strontium atoms inside a
      kagome-lattice hollow-core photonic crystal fibre are transversely confined by an
      optical lattice to prevent atoms from interacting with the fibre wall. By
      confining at most one atom in each lattice site, to avoid atom-atom interactions
      and Doppler effect, a 7.8-kHz-wide spectrum is observed for the (1)S0-(3)P1(m=0)
      transition. Atoms singly trapped in a magic lattice in hollow-core photonic
      crystal fibres improve the optical depth while preserving atomic coherence time. 

PMID- 24934479
TI  - Diterpenoids- potential chemopreventive and chemotherapeutic agents in leukemia.
AB  - Leukemia remains a major cause of death in both developing as well as developed
      nations worldwide. Development of novel therapeutic approaches is perceived to be
      the best strategy to combat this disease. Availability of limited effective drugs
      with least side effects is the major hurdle in treating leukemia. Another major
      concern remains initiation and engagement of therapeutic strategies that may
      subvert or overcome drug-resistance. Deployment of plant-based molecules in
      therapeutic engagements is regarded to be the most apt approach to combat
      different forms of leukemia. Diterpenoids of natural origin have a broad range of
      therapeutic activities including anti-leukemic effect. In vitro and in vivo
      studies establish many diterpenoids from natural sources and their synthetic
      derivatives to have appreciable cytotoxic and apoptotic efficacies against a
      series of leukemic cells. This paper attempts to identify and describe
      diterpenoids with their plant sources and analyze the molecular mechanistic
      approaches underlying their effective apoptotic activities against leukemic cells
      studied till date. The present review article summarizes different categories of
      diterpenoids having various degrees of anti-leukemic activities and discusses the
      measures of overcoming the bio-availability issues of these natural molecules so
      that they can serve as extremely viable options in future leukemia therapy. 

PMID- 24934480
TI  - Platelet-rich plasma induces mixed osteogenic/osteoclastogenic phenotype in
      osteosarcoma SaOS-2 cells: role of TGF-beta.
AB  - Platelet-rich plasma (PRP) is widely used to promote tissue repair and accelerate
      osteogenesis, but there is no agreement about its mechanism of action. We
      characterized the modulatory effect of PRP on the in vitro osteoblast model SaOS
      2, by using cell motility/chemoattraction and osteogenesis/mineralization assays,
      and a series of osteogenic/ osteoclastogenic genomic markers. Scratch wound assay
      showed that PRP stimulates cell motility, while transwell assay revealed a strong
      chemoattraction. Alkaline phosphatase (ALP) and alizarin red-S assays showed that
      PRP induces slight, but significant, stimulations of ALP activity and
      mineralization. The TGF-beta inhibitor SB431542 reversed these effects, showing a
      main role for TGF-beta1 released by PRP. Analyses of gene expression by qRT-PCR,
      showed the upregulation of osteocalcin, osteopontin, osteoprotegerin, receptor
      activator of NFkappaB (RANK), and runt-related transcription factor 2 (RUNX2)
      genes, with a total reversion by SB431542 for osteoprotegerin and RANK, and a
      partial reversion for ostecalcin, osteopontin, and RUNX2. The use of PCR array
      technique revealed the upregulation of the cathepsin K gene. These data show that
      PRP induces the development of mixed osteogenic/osteoclastogenic traits in the
      SaOS-2 model. Such a behavior may favour in vivo bone resorption and
      reconstitution at post-surgery or post-traumatic sites. 

PMID- 24934481
TI  - Rising post-colectomy complications in children with ulcerative colitis despite
      stable colectomy rates in United States.
AB  - BACKGROUND AND AIMS: In children with ulcerative colitis, data on temporal
      colectomy trends and in-hospital post-colectomy complications are limited. Thus,
      we evaluated time trends in colectomy rates and post-colectomy complications in
      children with ulcerative colitis. METHODS: We identified all children (<=18years)
      with a diagnosis code of ulcerative colitis (ICD-9: 556.X) and a procedure code
      of colectomy (ICD-9: 45.8 and 45.7) in the Kids' Inpatient Database for 1997,
      2000, 2003, 2006 and 2009. The incidence of colectomies for pediatric ulcerative
      colitis was calculated and Poisson regression analysis was performed to evaluate
      the change in colectomy rates. In-hospital postoperative complication rates were
      assessed and predictors for postoperative complications were evaluated using
      multivariate logistic regression. RESULTS: The annual colectomy rate in pediatric
      ulcerative colitis was 0.43 per 100,000person-years, which was stable throughout
      the study period (P>.05). Postoperative complications were experienced in 25%,
      with gastrointestinal (13%) and infectious (9.3%) being the most common.
      Postoperative complication rates increased significantly by an annual rate of
      1.1% from 1997 to 2009 (P=.01). However, other independent predictors of
      postoperative complications were not identified. Patients with postoperative
      complications had significantly longer median length of stay (14.3days vs
      8.2days; P<.001) and higher median hospital charges per patient (US $81,567 vs US
      $55,461; P<.001) compared to those without complications. CONCLUSION: Colectomy
      rates across the United States in children with ulcerative colitis have remained
      stable between 1997 and 2009; however, in-hospital postoperative complication
      rates have increased.

PMID- 24934482
TI  - Endovascular approaches for morphologically unfavorable intracranial aneurysms:
      adjunctive coiling techniques versus flow diversion.

PMID- 24934483
TI  - Response to letter, 'Endovascular approaches for morphologically unfavorable
      intracranial aneurysms: adjunctive coiling techniques versus flow diversion'.

PMID- 24934484
TI  - A randomised, multicentre, double blind, placebo controlled trial to evaluate the
      efficacy and safety of cilostazol in patients with vasospastic angina.
AB  - OBJECTIVES: We conducted a randomised, double blind, placebo controlled trial to
      assess the efficacy and safety of cilostazol, a selective inhibitor of
      phosphodiesterase 3, in patients with vasospastic angina (VSA). BACKGROUND:
      Cilostazol has been shown to induce vascular dilatation, but its efficacy in
      patients with VSA is unknown. METHODS: Between October 2011 and July 2012, 50
      patients with confirmed VSA who had >=1 angina episodes/week despite amlodipine
      therapy (5 mg/day) were randomly assigned to receive either cilostazol (up to 200
      mg/day) or placebo for 4 weeks. All patients were given diaries to record the
      frequency and severity of chest pain (0-10 grading). The primary endpoint was the
      relative reduction of the weekly incidence of chest pain. RESULTS: Baseline
      characteristics were similar between the two groups. Among 49 evaluable patients
      (25 in the cilostazol group, 24 in the placebo group), the primary endpoint was
      significantly greater in the cilostazol group compared with the placebo group (
      66.5+/-88.6% vs -17.6+/-140.1%, respectively, p=0.009). The secondary endpoints,
      including a change in the frequency of chest pain (-3.7+/-0.5 vs -1.9+/-0.6,
      respectively, p=0.029), a change in the chest pain severity scale (-2.8+/-0.4 vs 
      1.1+/-0.4, respectively, p=0.003), and the proportion of chest pain-free patients
      (76.0% vs 33.3%, respectively, p=0.003) also significantly favoured cilostazol.
      Headache was the most common adverse event in both groups (40.0% vs 20.8%,
      respectively, p=0.217). CONCLUSIONS: Cilostazol is an effective therapy for
      patients with VSA uncontrolled by conventional amlodipine therapy, and has no
      serious side effects. TRIAL REGISTRATION NUMBER: NCT01444885.

PMID- 24934485
TI  - KRAS, EGFR, PDGFR-alpha, KIT and COX-2 status in carcinoma showing thymus-like
      elements (CASTLE).
AB  - BACKGROUND: CASTLE (Carcinoma showing thymus-like elements) is a rare malignant
      neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell
      carcinoma of the thymus with different biological behaviour and a better
      prognosis than anaplastic carcinoma of the thyroid. METHODS: We retrospectively
      investigated 6 cases of this very rare neoplasm in order to investigate the
      mutational status of KRAS, EGFR, PDGFR-alpha and KIT, as well as the
      immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly
      find new therapeutic targets. RESULTS: Diagnosis was confirmed by a moderate to
      strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and
      TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in
      nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs)
      could be detected in exon 12 of the PDGFR-alpha gene (rs1873778), in three cases
      SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found
      in the KIT and KRAS gene. CONCLUSIONS: All tumors showed a COX-2 expression as
      well as an EGFR expression except for one case and a wild-type KRAS status. No
      activating mutations in the EGFR, KIT and PDGFR-alpha gene could be detected. Our
      data may indicate a potential for targeted therapies, but if these therapeutic
      strategies are of benefit in CASTLE remains to be determined. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1658499296115016.

PMID- 24934486
TI  - Hypogonadotropic hypogonadism: new identification of testicular blood flow and
      varicocele after treatment with gonadotropins.
AB  - OBJECTIVE: To investigate testicular changes in patients with hypogonadotropic
      hypogonadism (HH) after treatment with gonadotropins. DESIGN: Patients with HH
      were investigated and followed before and after treatment. SETTING: Urology and
      andrology clinic of a teaching hospital. PATIENT(S): Consecutive male patients
      with diagnosed HH. INTERVENTION(S): All patients were treated with gonadotropins
      during the study period and later. MAIN OUTCOME MEASURE(S): The hormonal status
      and scrotal color Doppler ultrasound (CDUS) of patients was recorded before and
      after treatment. RESULT(S): Twenty-six patients with HH (ages 18-43 years) were
      followed for 8-29 months. After treatment, serum T and secondary sex characters
      improved in all and spermatogenesis developed in 61.5% of patients. Before
      treatment, testicular (intraparenchymal blood flow) was undetectable in all and
      barely detectable in three patients. This improved significantly to 4.53+/-5.44
      and 4.27+/-4.97 cm/second, respectively, after treatment. Subcapsular arterial
      flow and testicular size also improved significantly. Similarly, after treatment,
      transverse epididymal diameter (TED) increased significantly. At baseline, no
      patient had detectable varicocele on CDUS. After treatment, varicocele was
      demonstrable in 23% of patients. This finding was further evaluated
      retrospectively from our 76 HH patient files. None of them had varicocele before
      treatment, but after treatment 19.73% were found to have varicocele.
      CONCLUSION(S): Patients with HH responded to gonadotropins by improvement in
      testicular blood flow and increase in TED. In some patients, varicocele was found
      to develop after treatment.

PMID- 24934487
TI  - A prediction model for live birth and multiple births within the first three
      cycles of assisted reproductive technology.
AB  - OBJECTIVE: To develop a model predictive of live-birth rates (LBR) and multiple
      birth rates (MBR) for an individual considering assisted reproduction technology
      (ART) using linked cycles from Society for Assisted Reproductive Technology
      Clinic Outcome Reporting System (SART CORS) for 2004-2011. DESIGN: Longitudinal
      cohort. SETTING: Clinic-based data. PATIENT(S): 288,161 women with an initial
      autologous cycle, of whom 89,855 did not become pregnant and had a second
      autologous cycle and 39,334 did not become pregnant in the first and second
      cycles and had a third autologous cycle, with an additional 33,598 women who had
      a cycle using donor oocytes (first donor cycle). INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): LBRs and MBRs modeled by woman's age, body mass index,
      gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh
      embryos transferred, and cycle, using backward-stepping logistic regression with
      results presented as adjusted odds ratios (AORs) and 95% confidence intervals.
      RESULT(S): The LBRs increased in all models with prior full-term births, number
      of embryos transferred; in autologous cycles also with gravidity, diagnoses of
      male factor, and ovulation disorders; and in donor cycles also with the diagnosis
      of diminished ovarian reserve. The MBR increased in all models with number of
      embryos transferred and in donor cycles also with prior full-term births. For
      both autologous and donor cycles, transferring two versus one embryo greatly
      increased the probability of a multiple birth (AOR 27.25 and 38.90,
      respectively). CONCLUSION(S): This validated predictive model will be implemented
      on the Society for Assisted Reproductive Technology Web site (www.sart.org) so
      that patients considering initiating a course of ART can input their data on the
      Web site to generate their expected outcomes.

PMID- 24934488
TI  - Antimullerian hormone and antral follicle count are lower in female cancer
      survivors and healthy women taking hormonal contraception.
AB  - OBJECTIVE: To determine the impact of hormonal contraception (HC) on markers of
      ovarian reserve, including antimullerian hormone (AMH) and antral follicle count
      (AFC). DESIGN: Longitudinal prospective cohort. SETTING: University hospital.
      PATIENT(S): Young adult female cancer survivors and healthy similar-age women.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Participants were followed
      annually to determine hormone levels and for transvaginal ultrasound. Subjects
      who used HC within the preceding 3 months were considered to be exposed. Linear
      mixed effects models were used to incorporate repeated measures and adjust for
      potential confounders. RESULT(S): A total of 249 women (126 survivors, 123
      control subjects; average age 25.5 years) were followed for an average of 2.1
      visits and 2.15 years. After adjusting for confounders, AMH was found to be 21%
      lower among survivors using HC and 55% lower among control subjects using HC
      (relative risk [RR] 0.79, 95% confidence interval [CI] 0.68-0.93; and RR 0.45,
      95% CI 0.30-0.68; respectively). AFC was 20% lower among survivors and control
      subjects using HC (RR 0.80, 95% CI 0.69-0.93). When considering an individual
      subject, AMH was 17%-35% lower when a subject had recently used HC than when she
      had not (survivors: RR 0.83, 95% CI 0.75-0.93; control subjects: RR 0.65, 95% CI
      0.55-0.78), and AFC was 11% lower (RR 0.89, 95% CI 0.82-0.96). Additive HC
      exposure across multiple visits was not associated with differences in AMH or
      AFC. CONCLUSION(S): AMH and AFC are significantly lower among women with recent
      exposure to HC. AMH and AFC should be interpreted with caution when measured in
      the setting of recent hormone use.

PMID- 24934489
TI  - Tamoxifen co-administration during controlled ovarian hyperstimulation for in
      vitro fertilization in breast cancer patients increases the safety of fertility
      preservation treatment strategies.
AB  - OBJECTIVE: To evaluate the safety and efficacy of tamoxifen co-administration
      during conventional controlled ovarian hyperstimulation (COH) protocols for a
      fertility-preservation IVF cycle in breast cancer patients. DESIGN: Two groups:
      retrospective descriptive cohort study and prospective study. SETTING: Breast
      cancer oncology and fertility-preservation centers in a tertiary hospital.
      PATIENT(S): Two groups of breast cancer patients: premenopausal patients treated
      with adjuvant tamoxifen; and patients undergoing in vitro fertilization (IVF) for
      fertility preservation. INTERVENTION(S): Fertility-preservation cycles, tamoxifen
      co-administration during conventional IVF. MAIN OUTCOME MEASURE(S): Endocrine
      records, and IVF results. RESULT(S): Estradiol (E2) levels were chronically high
      (mean 2663 pmol/L, maximum: 10,000 pmol/L) in 38 of 46 breast cancer patients
      treated with adjuvant tamoxifen. Co-administration of tamoxifen (48 cycles)
      during conventional IVF or without tamoxifen (26 cycles), using either the long
      gonadotropin-releasing hormone-agonist or-antagonist protocols, resulted,
      respectively, in a mean of 12.65 and 10.2 oocytes retrieved, and 8.5 and 6.4
      embryos cryopreserved. Average peak E2 levels were 6,924 pmol/L and 5,093 pmol/L,
      respectively, but long-term recurrence risk (up to 10 years) was not increased.
      CONCLUSION(S): In breast cancer patients, co-administration of tamoxifen during
      conventional COH for fertility preservation does not interfere with IVF results.
      The high serum E2 levels during COH should be considered safe, as it simulates
      the high prevalence of persistently high serum E2 levels in premenopausal breast
      cancer patients safely treated with adjuvant tamoxifen.

PMID- 24934490
TI  - Single-donor and double-donor sperm intrauterine insemination cycles: does double
      intrauterine insemination increase clinical pregnancy rates?
AB  - OBJECTIVE: To compare the pregnancy outcomes in the setting of a single- vs.
      double-donor sperm intrauterine insemination (IUI) treatment cycle. DESIGN:
      Retrospective cohort study. SETTING: Large, private assisted reproductive
      technology practice. PATIENT(S): Donor sperm IUI recipients. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): There were 2,486
      double and 673 single-donor sperm IUI cycles. The two groups were similar for
      age, body mass index, and the number of prior cycles. The clinical pregnancy
      rates were similar between the two groups (single: 16.4% vs. double: 13.6%). In
      univariate regression analysis, age, total motile sperm, and diminished ovarian
      reserve (DOR) were associated with pregnancy. Generalized estimating equation
      models accounting for repeated measures, age, DOR and total motile sperm and the
      interactions of these factors demonstrated that single and double IUI had similar
      odds of pregnancy (odds ratio 1.12; 95% confidence interval, 0.96-1.44).
      Pregnancy rates remained similar between the two groups in matched comparison and
      other subgroup analyses. CONCLUSION(S): Single and double-donor IUI cycles had
      similar clinical pregnancy rates. This large data set did not demonstrate a
      benefit to routine double IUI in donor sperm cycles.

PMID- 24934491
TI  - DMRT1 mutations are rarely associated with male infertility.
AB  - OBJECTIVE: To study a potential association between male infertility and DMRT1
      mutations. DESIGN: Retrospective sequencing study. SETTING: University hospital.
      PATIENT(S): 171 patients with cryptozoospermia (sperm concentration<0.1
      million/mL, n=40) or nonobstructive azoospermia (n=131), and 215 normozoospermic
      controls. INTERVENTION(S): Sequence analysis of DMRT1. MAIN OUTCOME MEASURE(S):
      Identification of rare variants in DMRT1 that are associated with male
      infertility. RESULT(S): In total, we detected four putative pathogenic mutations
      in six patients (3.5%) and less frequently in two controls (0.9%). CONCLUSION(S):
      Point mutations of DMRT1 may be rarely associated with male infertility.

PMID- 24934492
TI  - Tranilast, an orally active antiallergic compound, inhibits extracellular matrix
      production in human uterine leiomyoma and myometrial cells.
AB  - OBJECTIVE: To determine the effect of tranilast (an antiallergic drug known to
      suppress fibrosis or to stabilize mast cells) on extracellular matrix production
      in human leiomyoma and myometrial cells. DESIGN: Laboratory study. SETTING:
      University-affiliated laboratory. PATIENT(S): Seven premenopausal women who were
      admitted to the hospital for myomectomy or hysterectomy. INTERVENTION(S): Cells
      were treated with tranilast (300 MUM) for 48 hours to measure extracellular
      matrix and activin-A expression by real-time reverse-transcription polymerase
      chain reaction and/or immunocytochemistry. MAIN OUTCOME MEASURE(S): The
      expression of fibronectin, collagen1A1, versican, and activin-A in myometrial and
      leiomyoma cells. RESULT(S): Tranilast decreased fibronectin, collagen 1A1, and
      versican messenger RNA (mRNA) expression in human primary leiomyoma cell culture.
      Similar results were found in an immortalized human leiomyoma cell line.
      Tranilast also decreased the mRNA expression of fibronectin, collagen 1A1, and
      versican in human primary myometrial cells. The reduced expression of fibronectin
      and collagen 1 were observed by immunocytochemistry as well. Tranilast also
      reduced profibrotic growth factor, activin-A mRNA expression in primary
      myometrial and leiomyoma cells. CONCLUSION(S): Our results indicate that
      tranilast reduced fibronectin, collagen 1A1, versican, and activin-A expression
      in leiomyoma and myometrial cells, demonstrating its potential as an antifibrotic
      therapy for human leiomyomas.

PMID- 24934493
TI  - Toward the identification of a subset of unexplained infertility: a sperm
      proteomic approach.
AB  - OBJECTIVE: To investigate the male gamete proteome and its relation to blastocyst
      development and reproductive success. DESIGN: Experimental study. SETTING:
      Research laboratory. PATIENT(S): Male infertility patients (n=12) with no known
      male factor infertility, donated motile sperm after intracytoplasmic sperm
      injection during an oocyte donor in vitro fertilization cycle. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Proteomic profiles of sperm from normozoospermic
      males. RESULT(S): Patients were grouped based on day-5 embryo development: group
      A=good blastocyst development (>35%>=grade 3 BB) and group B=poor blastocyst
      development (<15%>=grade 3 BB). No differences between the groups were observed
      for sperm concentration, motility, or Kruger morphology. The in vitro
      fertilization outcome was statistically significantly different with higher
      viable implantation rates observed for group A (A=80% vs. B=48%). Proteomic
      analysis of the motile sperm samples revealed 49 proteins with statistically
      significantly differential abundance in relation to blastocyst development (>1.5
      fold). Twenty-nine proteins showed decreased abundance for group B, including
      several proteins involved in spermatogenesis, and 20 proteins showed increased
      abundance for group B, including several heat shock proteins. CONCLUSION(S): An
      altered sperm proteome was observed with respect to poor blastocyst development
      and in vitro fertilization outcome in donor oocyte cycles despite normal sperm
      testing parameters. These data could represent a novel subset of male factor
      infertility. Ongoing investigation into the male factor contribution to
      idiopathic infertility may result in improved patient care and enhanced outcomes.

PMID- 24934495
TI  - Increasing detection of rheumatic heart disease with echocardiography.
AB  - Rheumatic heart disease (RHD) is estimated to affect over 20 million people
      worldwide, the vast majority being in developing countries. Screening for RHD has
      been recommended by the WHO since 2004. Conventionally, auscultation has been
      used for diagnosing RHD. Auscultation has its limitation and may not detect mild
      cases. A large number of studies have reported echocardiographic screening for
      RHD over the last several years. Most of these studies report an almost 10-fold
      higher prevalence of RHD by echocardiography as compared to conventional method
      of auscultation. Early diagnosis of such mild cases may be important as
      instituting secondary prophylaxis in such cases may reduce the burden of the
      disease. However, several concerns remain about the significance and natural
      history of these minor valvular changes detected by echocardiography. Whether
      secondary prophylaxis will reverse these abnormalities is also unclear. Long term
      follow up studies are required to answer some of these concerns. 

PMID- 24934494
TI  - "Missing pieces"--functional, social, and environmental barriers to recovery for
      vulnerable older adults transitioning from hospital to home.
AB  - OBJECTIVES: To describe barriers to recovery at home for vulnerable older adults
      after leaving the hospital. DESIGN: Standard qualitative research techniques,
      including purposeful sampling of participants according to age, sex, race, and
      English proficiency, were used to ensure a wide breadth of experiences. All
      participants were interviewed in their native language (English, Spanish, or
      Chinese). Two investigators independently coded interviews using the constant
      comparative method. The entire research team, with diverse backgrounds in primary
      care, hospital medicine, geriatrics, and nursing, performed thematic analysis.
      SETTING: Urban public safety-net teaching hospital. PARTICIPANTS: Vulnerable
      older adults (low income and health literacy, limited English proficiency)
      enrolled in a larger discharge interventional study. MEASUREMENTS: Qualitative
      data (participant quotations) were organized into themes. RESULTS: Twenty-four
      individuals with a mean age of 63 (range 55-84), 66% male, 67% nonwhite, 16%
      Spanish speaking, 16% Chinese speaking were interviewed. An overarching theme of
      "missing pieces" was identified in the plan for postdischarge recovery at home,
      from which three specific subthemes emerged: functional limitations and
      difficulty with mobility and self-care tasks, social isolation and lack of
      support from family and friends, and challenges from poverty and the built
      environment at home. In contrast, participants described mostly supportive
      experiences with traditional focuses of transition, care such as following
      prescribed medication and diet regimens. CONCLUSION: Hospital-based discharge
      interventions that focus on traditional aspects of care may overlook social and
      functional gaps in postdischarge care at home for vulnerable older adults.
      Postdischarge interventions that address these challenges may be necessary to
      reduce readmissions in this population.

PMID- 24934496
TI  - The non-cardiac use and significance of cardiac troponins.
AB  - Cardiac Troponins are blood markers of myocardial damage and are widely utilised
      across all acute medical departments. However, with a massive rise in requests
      for this test, the interpretation of raised serum levels in the absence of
      cardiac sounding clinical features can become a clinical conundrum. This is
      especially true if the numerous causes of positive test results are not fully
      appreciated. A thorough understanding of the strengths and weaknesses of this
      blood test in light of a patient population living longer, increasing in
      comorbidities and possible causes of false test results can provide invaluable
      support in establishing an accurate diagnosis and instigating effective
      management. This article will describe the history of cardiac markers along with
      a discussion of the various causes of elevated cardiac troponins outside acute
      coronary syndrome. It will elaborate on the applications and significance of this
      blood test and the potential uses of positive results with elevated serum
      Troponin levels. 

PMID- 24934497
TI  - India's medical colleges lose 16,000 seats because of poor standards.

PMID- 24934498
TI  - Real-life use of vitamin D3-fortified bread and milk during a winter season: the
      effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish
      families, the VitmaD study.
AB  - Common genetic variants rs10741657 and rs10766197 in CYP2R1 and rs4588 and
      rs842999 in GC and a combined genetic risk score (GRS) of these four variants
      influence late summer 25-hydroxyvitamin D (25(OH)D) concentrations. The
      objectives were to identify those who are most at risk of developing low vitamin
      D status during winter and to assess whether vitamin D3-fortified bread and milk
      will increase 25(OH)D concentrations in those with genetically determined low
      25(OH)D concentrations at late summer. We used data from the VitmaD study.
      Participants were allocated to either vitamin D3-fortified bread and milk or non
      fortified bread and milk during winter. In the fortification group, CYP2R1
      (rs10741657) and GC (rs4588 and rs842999) were statistically significantly
      associated with winter 25(OH)D concentrations and CYP2R1 (rs10766197) was
      borderline significant. There was a negative linear trend between 25(OH)D
      concentrations and carriage of 0-8 risk alleles (p < 0.0001). No association was
      found for the control group (p = 0.1428). There was a significant positive linear
      relationship between different quintiles of total vitamin D intake and the
      increase in 25(OH)D concentrations among carriers of 0-2 (p = 0.0012), 3 (p =
      0.0001), 4 (p = 0.0118) or 5 (p = 0.0029) risk alleles, but not among carriers of
      6-8 risk alleles (p = 0.1051). Carriers of a high GRS were more prone to be
      vitamin D deficient compared to carriers of a low GRS. Furthermore, rs4588-AA
      carriers have a low but very stable 25(OH)D concentration, and interestingly,
      also low PTH level. 

PMID- 24934499
TI  - Roofed grooves: rapid layer engineering of perfusion channels in collagen tissue
      models.
AB  - Surface patterning (micro-moulding) of dense, biomimetic collagen is a simple
      tool to produce complex tissues using layer-by-layer assembly. The aim here was
      to channelise three-dimensional constructs for improved perfusion. Firstly,
      collagen fibril accumulation was measured by comparative image analysis to
      understand the mechanisms of structure formation in plastically compressed
      collagen during u-moulding. This showed that shape (circular or rectangular) and
      dimensions of the template affected collagen distribution around moulded grooves
      and consequently their stability. In the second part, this was used for effective
      fabrication of multi-layered plastically compressed collagen constructs with
      internal channels by roofing the grooves with a second layer. Using rectangular
      templates of 25/50/100 um widths and 75 um depth, grooves were u-moulded into the
      fluid-leaving surface of collagen layers with predictable width/depth fidelities.
      These grooves were then roofed by addition of a second plastically compressed
      collagen layer on top to produce u-channels. Resulting u-channels retained their
      dimensions and were stable over time in culture with fibroblasts and could be
      cell seeded with a lining layer by simple transfer of epithelial cells. The
      results of this study provide a valuable platform for rapid fabrication of
      complex collagen-based tissues in particular for provision of perfusing
      microchannels through the bulk material for improved core nutrient supply. 

PMID- 24934502
TI  - Immunomodulatory effects of hyperthermia on resisting WSSV infection in
      Procambarus clarkii.
AB  - White spot disease remains a constant threat to aquaculture worldwide.
      Hyperthermia has been shown to reduce mortality in white spot syndrome virus
      (WSSV)-infected shrimps, but the mechanism still remains unclear. In this study,
      we sought to identify host immune factors that contribute to inhibition of WSSV
      infection during hyperthermia. In WSSV-infected red swamp crayfish Procambarus
      clarkii (Girard) cultured at 24 +/- 1  degrees C, transcriptional levels of the
      heat shock protein 70 (Hsp70) gene showed a modest, 2.2-fold increase in
      haemocytes following 48 h post-infection (hpi). In contrast, in WSSV-infected
      crayfish cultured at 32 +/- 1  degrees C, Hsp70 gene expression showed a rapid,
      19.5-fold induction by 4 hpi. This suggests that Hsp70 plays a positive
      regulatory role in resistance to WSSV infection during hyperthermia. Furthermore,
      total haemocyte counts (THC) and phenoloxidase (PO) activity were both
      significantly increased in WSSV-infected crayfish cultured at 32 +/- 1  degrees C
      by 48 hpi. Both may be critical for crayfish survival in the late stages of WSSV
      infection. Collectively, the up-regulation of host protein Hsp70 expression and
      increase in THC and PO activity suggest that hyperthermia has immunomodulatory
      effect that enhanced the resistance of P. clarkii to WSSV infection. 

PMID- 24934500
TI  - Development and hemocompatibility testing of nitric oxide releasing polymers
      using a rabbit model of thrombogenicity.
AB  - Hemocompatibility is the goal for any biomaterial contained in extracorporeal
      life supporting medical devices. The hallmarks for hemocompatibility include
      nonthrombogenicity, platelet preservation, and maintained platelet function. Both
      in vitro and in vivo assays testing for compatibility of the blood/biomaterial
      interface have been used over the last several decades to ascertain if the
      biomaterial used in medical tubing and devices will require systemic
      anticoagulation for viability. Over the last 50 years systemic anticoagulation
      with heparin has been the gold standard in maintaining effective extracorporeal
      life supporting. However, the biomaterial that maintains effective ECLS without
      the use of any systemic anticoagulant has remained elusive. In this review, the
      in vivo 4-h rabbit thrombogenicity model genesis will be described with emphasis
      on biomaterials that may require no systemic anticoagulation for extracorporeal
      life supporting longevity. These novel biomaterials may improve extracorporeal
      circulation hemocompatibility by preserving near resting physiology of the major
      blood components, the platelets and monocytes. The rabbit extracorporeal
      circulation model provides a complete assessment of biomaterial interactions with
      the intrinsic coagulation players, the circulating platelet and monocytes. This
      total picture of blood/biomaterial interaction suggests that this rabbit
      thrombogenicity model could provide a standardization for biomaterial
      hemocompatibility testing. 

PMID- 24934501
TI  - Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes
      at age 6 years.
AB  - IMPORTANCE: Breastfeeding is known to have beneficial effects, but concern exists
      that breastfeeding during maternal antiepileptic drug (AED) therapy may be
      harmful. We previously noted no adverse effects of breastfeeding associated with
      AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school
      performance and adult abilities. OBJECTIVES: To examine the effects of AED
      exposure via breastfeeding on cognitive functions at age 6 years. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective observational multicenter study of long
      term neurodevelopmental effects of AED use. Pregnant women with epilepsy
      receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate)
      were enrolled from October 14, 1999, through April 14, 2004, in the United States
      and the United Kingdom. At age 6 years, 181 children were assessed for whom we
      had both breastfeeding and IQ data. All mothers in this analysis continued taking
      the drug after delivery. MAIN OUTCOMES AND MEASURES: Differential Ability Scales
      IQ was the primary outcome. Secondary measures included measures of verbal,
      nonverbal, memory, and executive functions. For our primary analysis, we used a
      linear regression model with IQ at age 6 years as the dependent variable,
      comparing children who breastfed with those who did not. Similar secondary
      analyses were performed for the other cognitive measures. RESULTS: In total,
      42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and
      duration did not differ across drug groups. The IQ at age 6 years was related to
      drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared
      to other drugs]), drug dosage (regression coefficient, -0.1; 95% CI, -0.2 to 0.0;
      P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95% CI,
      0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception
      folate use (adjusted IQ 6 [95% CI, 2-10] points higher for folate, P = .005), and
      breastfeeding (adjusted IQ 4 [95% CI, 0-8] points higher for breastfeeding, P =
      .045). For the other cognitive domains, only verbal abilities differed between
      the breastfed and nonbreastfed groups (adjusted verbal index 4 [95% CI, 0-7]
      points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE: No
      adverse effects of AED exposure via breast milk were observed at age 6 years,
      consistent with another recent study at age 3 years. In our study, breastfed
      children exhibited higher IQ and enhanced verbal abilities. Additional studies
      are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00021866.

PMID- 24934503
TI  - Affinity purification probes of potential use to investigate the endogenous Hsp70
      interactome in cancer.
AB  - Heat shock protein 70 (Hsp70) is a family of proteins with key roles in
      regulating malignancy. Cancer cells rely on Hsp70 to inhibit apoptosis, regulate
      senescence and autophagy, and maintain the stability of numerous onco-proteins.
      Despite these important biological functions in cancer, robust chemical tools
      that enable the analysis of the Hsp70-regulated proteome in a tumor-by-tumor
      manner are yet unavailable. Here we take advantage of a recently reported Hsp70
      ligand to design and develop an affinity purification chemical toolset for
      potential use in the investigation of the endogenous Hsp70-interacting proteome
      in cancer. We demonstrate that these tools lock Hsp70 in complex with onco-client
      proteins and effectively isolate Hsp70 complexes for identification through
      biochemical techniques. Using these tools we provide proof-of-concept analyses
      that glimpse into the complex roles played by Hsp70 in maintaining a multitude of
      cell-specific malignancy-driving proteins. 

PMID- 24934504
TI  - Deficits in discrimination after experimental frontal brain injury are mediated
      by motivation and can be improved by nicotinamide administration.
AB  - One of the largest challenges in experimental neurotrauma work is the development
      of models relevant to the human condition. This includes both creating similar
      pathophysiology as well as the generation of relevant behavioral deficits. Recent
      studies have shown that there is a large potential for the use of discrimination
      tasks in rats to detect injury-induced deficits. The literature on discrimination
      and TBI is still limited, however. The current study investigated motivational
      and motor factors that could potentially contribute to deficits in
      discrimination. In addition, the efficacy of a neuroprotective agent,
      nicotinamide, was assessed. Rats were trained on a discrimination task and
      motivation task, given a bilateral frontal controlled cortical impact TBI (+3.0
      AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor
      ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI
      resulted in large deficits in discrimination and motivation. No deficits were
      observed on gross motor measures; however, the vehicle group showed impairments
      in fine motor control. Both injured groups were impaired on the reference memory
      MWM, but only nicotinamide-treated rats were impaired on the working memory MWM.
      Nicotinamide administration improved performance on discrimination and motivation
      measures. Experiment 2 evaluated retraining on the discrimination task and
      suggested that motivation may be a large factor underlying discrimination
      deficits. Retrained rats improved considerably on the discrimination task. The
      tasks evaluated in this study demonstrate robust deficits and may improve the
      detection of pharmaceutical effects by being very sensitive to pervasive
      cognitive deficits that occur after frontal TBI.

PMID- 24934505
TI  - Uncommon serum creatine phosphokinase and lactic dehydrogenase increase during
      diosmin therapy: two case reports.
AB  - INTRODUCTION: Short-term administration of diosmin is usually considered safe,
      with only minor side effects (stomach and abdominal pain, diarrhea,
      dermatological disorders, and headache) occasionally observed. Within a 4-year
      period, a general practitioner noticed 17 cases of mild, diosmin-induced side
      effects, two of which showed particular interest. CASES PRESENTATION: Case 1: A
      55-year-old Caucasian woman presented with chronic leg venous insufficiency. She
      was prescribed diosmin 450 mg twice a day. After 5 days of therapy, she developed
      pain in the legs (myalgia), and diosmin therapy was suspended. She made a
      spontaneous attempt of drug rechallenge and her leg pain reappeared. Thus, she
      underwent blood analysis, which showed elevation of creatine phosphokinase
      levels. Creatine phosphokinase values normalized only after prolonged
      discontinuation of the therapy. Case 2: A 79-year-old Caucasian man, who was
      diagnosed with acute hemorrhoidal syndrome. After 21 days of continuous diosmin
      treatment, increased levels of serum lactic dehydrogenase were detected. In both
      cases a comprehensive analysis of all possible causes for enzyme elevation was
      made. CONCLUSIONS: A feasible hypothesis to explain these rare effects could be
      that exaggerated adrenergic activity occurred on microcirculation, leading to an
      excessive peripheral vasoconstriction and subsequent ischemic damage. An
      individual predisposition is strongly suggested. A concurrence of events was
      probably responsible for the elevation of nonspecific tissue necrosis markers.
      Physicians and patients must be aware of these rare, but possible, adverse drug
      reactions.

PMID- 24934507
TI  - Semimetallic molybdenum disulfide ultrathin nanosheets as an efficient
      electrocatalyst for hydrogen evolution.
AB  - Molybdenum disulfide (MoS2) ultrathin nanosheets, as a well-known inorganic two
      dimensional (2D) material with a graphene-like structure, has attracted
      tremendous attention due to its unique microscopic and macroscopic properties
      brought by the confinement of charge and heat transfer upon the basal plane.
      However, as the prototype Mott-insulator, its relatively low conductivity and
      carrier concentration still greatly hamper its wide applications. Here, we
      developed a novel intralayer vanadium-doping strategy to produce semimetallic
      vanadium-doped MoS2 (VMS) ultrathin nanosheets with less than five S-(V, Mo)-S
      atomic layers, as a new inorganic 2D material. By incorporation of intralayer
      vanadium atoms, fine regulation of intrinsic electrical properties within the
      pristine MoS2 structure has been successfully realized, achieving semimetallic
      MoS2-based 2D materials with tunable conductivity and higher carrier
      concentration for the first time. Benefiting from the enhanced in-plane
      conductivity, the improved carrier concentration as well as the shortened
      electron transfer paths, the semimetal-like VMS nanosheet have enhanced catalytic
      activity with an overpotential of 0.13 V and a smaller Tafel slope, exhibiting
      enhanced catalytic performance compared with that of a pure MoS2 system. The
      intralayer doping in the 2D structure opens a new avenue in building highly
      efficient catalysts through the regulation of their intrinsic electrical
      properties, and also gives a new perspective for enlarging the design space of 2D
      materials.

PMID- 24934508
TI  - Synthesis and anti-TMV activity of novel beta-amino acid ester derivatives
      containing quinazoline and benzothiazole moieties.
AB  - Here, a series of beta-amino acid ester derivatives containing quinazoline and
      benzothiazoles was synthesized and evaluated for anti-tobacco mosaic virus (TMV)
      activity. The compounds 3n, 3o, 3p and 3q showed good antiviral activity against
      TMV at a concentration of 500 MUg/mL, with curative rates of 55.55%, 52.32%,
      52.77% and 50.91%, respectively, and protection rates of 52.33%, 55.96%, 54.21%
      and 50.98%, respectively. These values were close to those of the commercially
      available antiviral agent ningnanmycin (which has curative and protection rates
      of 55.27% and 52.16%, respectively). To our knowledge, this is the first report
      of the anti-TMV activity of beta-amino acid ester derivatives containing
      quinazoline and benzothiazoles moieties; the results indicate that these novel
      compounds can potentially be used as protective agents against TMV diseases.

PMID- 24934506
TI  - GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to
      be a major locus for skin fluorescence.
AB  - AIMS/HYPOTHESIS: Skin fluorescence (SF) is a non-invasive marker of AGEs and is
      associated with the long-term complications of diabetes. SF increases with age
      and is also greater among individuals with diabetes. A familial correlation of SF
      suggests that genetics may play a role. We therefore performed parallel genome
      wide association studies of SF in two cohorts. METHODS: Cohort 1 included 1,082
      participants, 35-67 years of age with type 1 diabetes. Cohort 2 included 8,721
      participants without diabetes, aged 18-90 years. RESULTS: rs1495741 was
      significantly associated with SF in Cohort 1 (p < 6 * 10(-10)), which is known to
      tag the NAT2 acetylator phenotype. The fast acetylator genotype was associated
      with lower SF, explaining up to 15% of the variance. In Cohort 2, the top signal
      associated with SF (p = 8.3 * 10(-42)) was rs4921914, also in NAT2, 440 bases
      upstream of rs1495741 (linkage disequilibrium r (2) = 1.0 for rs4921914 with
      rs1495741). We replicated these results in two additional cohorts, one with and
      one without type 1 diabetes. Finally, to understand which compounds are
      contributing to the NAT2-SF signal, we examined 11 compounds assayed from skin
      biopsies (n = 198): the fast acetylator genotype was associated with lower levels
      of the AGEs hydroimidazolones of glyoxal (p = 0.017). CONCLUSIONS/INTERPRETATION:
      We identified a robust association between NAT2 and SF in people with and without
      diabetes. Our findings provide proof of principle that genetic variation
      contributes to interindividual SF and that NAT2 acetylation status plays a major
      role.

PMID- 24934509
TI  - Germinal center reaction: antigen affinity and presentation explain it all.
AB  - The selection and expansion of B cells undergoing affinity maturation in the
      germinal center is a hallmark of humoral immunity. A recent paper in Nature
      provides new insights into the relationships between the affinity of the
      immunoglobulin receptor for antigen, the ability of B cells to present antigen to
      T cells, and the processes of selection, mutation, and clonal expansion in the
      germinal center. 

PMID- 24934511
TI  - The angiogenic behaviors of human umbilical vein endothelial cells (HUVEC) in co
      culture with osteoblast-like cells (MG-63) on different titanium surfaces.
AB  - OBJECTIVES: Interaction between osteogenesis and angiogenesis plays an important
      role in implant osseointegration. In the present study we investigated the
      influence of titanium surface properties on the angiogenic behaviors of
      endothelial cells grown in direct contact co-culture with osteoblasts. METHODS:
      Human umbilical vein endothelial cells (HUVECs) and osteoblast-like cells (MG-63
      cells) were grown in direct co-culture on the following titanium surfaces: acid
      etched (A), hydrophilic A (modA), coarse-gritblasted and acid-etched (SLA) and
      hydrophilic SLA (SLActive). Cell proliferation was evaluated by cell counting
      combined with flow cytometry. The expression of von Willebrand Factor (vWF),
      thrombomodulin (TM), endothelial cell protein C receptor (EPCR), E-Selectin, as
      well as vascular endothelial growth factor (VEGF) receptors Flt-1 and KDR in
      HUVECs and VEGF in MG-63 were measured by qPCR. The dynamic behavior of
      endothelial cells was recorded by time-lapse microscopy. RESULTS: Proliferation
      of HUVECs was highest on A, followed by SLA, modA and SLActive surfaces. The
      expression of vWF, TM, EPCR, E-Selectin and Flt-1 in HUVECs was significantly
      higher on A than on all other surfaces. The expression of KDR in HUVECs grown on
      A surface was below detection limit. VEGF expression in MG-63 cells was
      significantly higher on SLActive vs SLA and modA vs A surfaces. Time-lapse
      microscopy revealed that HUVECs moved quickest and formed cell clusters earlier
      on A surface, followed by SLA, modA and SLActive surface. CONCLUSIONS: In co
      culture conditions, proliferation and expression of angiogenesis associated genes
      in HUVECs are promoted by smooth hydrophobic Ti surface, which is in contrast to
      previous mono-culture studies.

PMID- 24934512
TI  - Editorial: advances in computational structure based drug discovery.

PMID- 24934510
TI  - Phenotyping animal models of diabetic neuropathy: a consensus statement of the
      diabetic neuropathy study group of the EASD (Neurodiab).
AB  - NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting
      to explore the current status of animal models of diabetic peripheral neuropathy.
      The goal of the workshop was to develop a set of consensus criteria for the
      phenotyping of rodent models of diabetic neuropathy. The discussion was divided
      into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve
      structure, (3) electrophysiological assessments of nerve function, (4) behavioral
      assessments of nerve function, and (5) the role of biomarkers in disease
      phenotyping. Participants discussed the current understanding of each area, gold
      standards (if applicable) for assessments of function, improvements of existing
      techniques, and utility of known and exploratory biomarkers. The research
      opportunities in each area were outlined, providing a possible roadmap for future
      studies. The meeting concluded with a discussion on the merits and limitations of
      a unified approach to phenotyping rodent models of diabetic neuropathy and a
      consensus formed on the definition of the minimum criteria required for
      establishing the presence of the disease. A neuropathy phenotype in rodents was
      defined as the presence of statistically different values between diabetic and
      control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction
      velocities, or nerve structure). The participants propose that this framework
      would allow different research groups to compare and share data, with an emphasis
      on data targeted toward the therapeutic efficacy of drug interventions. 

PMID- 24934513
TI  - [Intraoperative monitoring of oxygen tissue pressure: Applications in vascular
      neurosurgery].
AB  - Ischemic lesions related to surgical procedures are a major cause of
      postoperative morbidity in patients with cerebral vascular disease. There are
      different systems of neuromonitoring to detect intraoperative ischemic events,
      including intraoperative monitoring of oxygen tissue pressure (PtiO2). The aim of
      this article was to describe, through the discussion of 4 cases, the usefulness
      of intraoperative PtiO2 monitoring during vascular neurosurgery. In presenting
      these cases, we demonstrate that monitoring PtiO2 is a reliable way to detect
      early ischemic events during surgical procedures. Continuous monitoring of PtiO2
      in an area at risk allows the surgeon to resolve the cause of the ischemic event
      before it evolves to an established cerebral infarction. 

PMID- 24934514
TI  - Colorectal cancer: from the laboratory to the patient, a now indispensable step.

PMID- 24934515
TI  - Cavo-atrial metastases from cutaneous melanoma.

PMID- 24934517
TI  - Application of the wireless electroencephalogram to measure stress in White Pekin
      ducks.
AB  - Stress in poultry can produce many undesirable effects on bird health and
      production performance. The objective of this study was to develop and evaluate a
      potential measure to assess stress through analysis of brain activity using
      electroencephalography (EEG). In two experiments, White Pekin ducks were
      implanted with EEG transmitters and treated with potential stressors in a chamber
      or in their pens. Electrocardiograms and blood corticosterone levels were
      collected as standard measures of stress. EEG analysis showed an increase in the
      relative delta frequency and a decrease in the relative alpha frequency during
      the treatment period for shock (P < 0.05). EEG analysis of the second experiment
      showed no differences between time periods for all frequencies for all
      treatments. Based on these results, EEG is currently not a viable technique for
      the measurement of acute stress in commercial poultry. 

PMID- 24934516
TI  - Association of CXCR1 polymorphisms with apoptosis, necrosis and concentration of
      milk neutrophils in early lactating dairy heifers.
AB  - Associations between polymorphisms in the candidate gene CXCR1, encoding the
      chemokine (C-X-C motif) receptor 1, and udder health have been identified before.
      In the present study, associations between the CXCR1 genotype (whole coding
      region) and apoptosis, necrosis, and concentration of milk polymorphonuclear
      neutrophilic leukocyte (PMNL) of 292 quarters belonging to 73 early lactating
      dairy heifers were studied. In uninfected quarters, % milk PMNL apoptosis was
      higher in c.980GG heifers [least squares means (LSM) 27%] compared to c.980AG
      heifers (LSM 16%), whereas in infected quarters, % milk PMNL apoptosis was higher
      in c.642GG heifers (LSM 29%) compared to c.642AG heifers (LSM 18%). Differences
      in milk PMNL concentration between infected and uninfected quarters were smaller
      in c.980AG heifers than in c.980GG heifers. An association between the CXCR1
      genotype and necrosis of milk PMNL could not be demonstrated. Results indicate
      that CXCR1 polymorphisms influence viability and concentration of milk PMNL and
      provide a foundation for future research. 

PMID- 24934518
TI  - Intra-population chemical polymorphism in Thymus pannonicus All. growing in
      Slovakia.
AB  - Solid-phase microextraction technique coupled with gas chromatography-flame
      ionisation detector and gas chromatography-mass spectrometry was used to
      investigate the inter- and intra-population chemical polymorphism in volatile
      constituents of three populations of Thymus pannonicus growing in Slovakia. To
      have an idea on what really the plant emits under different environmental and
      physiological conditions, a total of 86 individuals were separately analysed
      using low extraction temperatures (30 degrees C). Data were analysed using a
      chemometric approach such as the principal component analysis which revealed a
      significant intra-population variability with the existence of up to four
      chemotypes: the most abundant is the p-cymene/gamma-terpinene chemotype, followed
      by the geraniol and linalool chemotypes, and, only in one population, by the
      gamma-muurolene/(E)-caryophyllene chemotype. This differentiation of individual
      plants inside the populations allows better adaptation to ecological conditions
      of localities and is probably connected with intrinsic genetic diversity of the
      species. 

PMID- 24934519
TI  - Efficiency of RAFT-synthesized PDMAEMA in gene transfer to the retina.
AB  - Gene therapy has long been heralded as the new hope to evolve from symptomatic
      care of genetic pathologies to a full cure. Recent successes in using gene
      therapy for treating several ocular and haematopoietic pathologies have shown the
      great potential of this approach that, in the early days, relied on the use of
      viral vectors, which were considered by many to be undesirable for human
      treatment. Therefore, there is considerable interest and effort in developing non
      viral vectors, with efficiency close to that of viral vectors. The aim of this
      study was to develop suitable non-viral carriers for gene therapy to treat
      pathologies affecting the retina. In this study poly(2-(N,N-dimethylamino)ethyl
      methacrylate), PDMAEMA was synthesized by reversible addition-fragmentation chain
      transfer (RAFT) and the in vitro cytocompatibility and transfection efficiency of
      a range of polymer:DNA ratios evaluated using a retinal cell line; in vivo
      biocompatibility was evaluated by ocular injection in C57BL/6 mice. The results
      showed that through RAFT, it is possible to produce a defined-size polymer that
      is compatible with cell viability in vitro and capable of efficiently directing
      gene expression in a polymer-DNA ratio-dependent manner. When injected into the
      eyes of mice, these vectors induced a transient, mild inflammation,
      characteristic of the implantation of medical devices. These results form the
      basis of future studies where RAFT-synthesized PDMAEMA will be used to deliver
      gene expression systems to the retina of mouse models of retinal pathologies.
      Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24934520
TI  - A nomogram for calculation of the Revised Baux Score.
AB  - Since its original publication, the revised Baux score for mortality prediction
      in burns patients has been widely adopted. It uses readily available measures,
      and it is based on regression analysis from actual data rather than a theoretical
      model. However, the necessary calculations are too complex to perform with
      anything other than a scientific calculator or dedicated software, which may
      create issues in a clinical setting where access to electronic devices may be
      limited. We designed a nomogram capable of performing the calculation to a high
      degree of accuracy, and evaluated its performance on a set of randomly generated
      patient data to ensure that the nomogram gives accurate and repeatable results.
      The nomogram has a bias of -0.003 percentage points, with limits of agreement 
      0.3619 to 0.3550 and a repeatability coefficient of 0.29 percentage points. We
      feel that the nomogram's accuracy, low cost, speed and ease of use would make it
      a very useful adjunct during the initial assessment of burns patients. It could
      also realistically be used to crosscheck calculations made by other methods. 

PMID- 24934521
TI  - Rehabilitation and social adjustment of people with burns in society.
AB  - The present study was conducted on rehabilitation and social adjustment of people
      with burns in society with the main objective to determine the relationship
      between social adjustment of people with burns and their psychosocial
      rehabilitation. The study was limited to the Burn Unit, Khyber Teaching Hospital,
      Peshawar, Pakistan. At bi-variate level, the following were observed: the
      relationship of psychosocial rehabilitation was highly significant (P=0.000)
      considering that people with burns feel shame in the society, a highly
      significant relation (P=0.000) was found between psychosocial rehabilitation and
      burn as the hurdle to contact other members of the society, a highly significant
      (P=0.000) relation was found between psychosocial rehabilitation and perception
      that society provides social support to people with burns, a highly significant
      (P=0.000) relationship between psychosocial rehabilitation and people with burns
      feel alienated from the society, a significant association (P=0.024) was found
      between psychosocial rehabilitation and loss of social network, and a significant
      (P=0.002) association between psychosocial rehabilitation and society insult
      toward people with burns. Regular provision of treatment, quota in job allocation
      for people with burns, initiation of stipend through Benazir Income Support
      Program, and keeping and updating record of burns at the district level in census
      centers were suggested as recommendations in light of the study. 

PMID- 24934523
TI  - Warfarin, genes, and the (health care) environment.

PMID- 24934524
TI  - Combination therapy of bezafibrate and ursodeoxycholic acid for primary biliary
      cirrhosis: A meta-analysis.
AB  - The aim of this study was to assess the efficiency and safety of combination
      therapy of ursodeoxycholic acid (UDCA) and bezafibrate for primary biliary
      cirrhosis. A meta-analysis of all long-term randomized controlled trials
      comparing the combination of UDCA and bezafibrate with UDCA monotherapy was
      performed via electronic searches. Seven trials, which included 177 patients,
      were assessed. Combination therapy with UDCA and bezafibrate was more effective
      than UDCA monotherapy in improving liver biochemistry, alkaline phosphatase (mean
      difference [MD], -146.15 IU/L; 95% confidence interval [CI], -193.58 to -98.72; P
      < 0.00001), gamma-glutamyltransferase (MD, -20.64 IU/L; 95% CI, -30.86 to -10.43;
      P < 0.0001), immunoglobulin M (MD, -90.96 mg/dL; 95% CI, -137.36 to -44.56; P =
      0.0001) and triglycerides (MD, -15.49 mg/dL; 95% CI, -30.25 to -0.74; P = 0.04).
      However, their effects on pruritus (odds ratio [OR], 0.82; 95% CI, 0.30-2.24; P =
      0.70) and alanine aminotransferase (MD, -8.41 IU/L; 95% CI, -22.57 to 5.75; P =
      0.24) did not differ significantly. This meta-analysis revealed no significant
      differences in the incidence of all-cause mortality (OR, 0.72; 95% CI, 0.10-5.49;
      P = 0.75) and adverse events (OR, 0.35; 95% CI, 0.07-1.84; P = 0.22) between
      patients treated with combination therapy and those treated with monotherapy. In
      this meta-analysis, combination therapy with UDCA and bezafibrate was more
      effective than UDCA monotherapy. Combination therapy improved liver biochemistry,
      but did not improve clinical symptoms, incidence of death or adverse events more
      effectively than monotherapy. 

PMID- 24934522
TI  - Survival data and predictors of functional outcome an average of 15 years after
      the Fontan procedure: the pediatric heart network Fontan cohort.
AB  - OBJECTIVE: Multicenter longitudinal outcome data for Fontan patients surviving
      into adulthood are lacking. The aim of this study was to better understand
      contemporary outcomes in Fontan survivors by collecting follow-up data in a
      previously well-characterized cohort. DESIGN: Baseline data from the Fontan Cross
      Sectional Study (Fontan 1) were previously obtained in 546 Fontan survivors aged
      11.9 +/- 3.4 years. We assessed current transplant-free survival status in all
      subjects 6.8 +/- 0.4 years after the Fontan 1 study. Anatomic, clinical, and
      surgical data were collected along with socioeconomic status and access to health
      care. RESULTS: Thirty subjects (5%) died or underwent transplantation since
      Fontan 1. Subjects with both an elevated (>21 pg/mL) brain natriuretic peptide
      and a low Child Health Questionnaire physical summary score (<44) measured at
      Fontan 1 were significantly more likely to die or undergo transplant than the
      remainder, with a hazard ratio of 6.2 (2.9-13.5). Among 516 Fontan survivors, 427
      (83%) enrolled in this follow-up study (Fontan 2) at 18.4 +/- 3.4 years of age.
      Although mean scores on functional health status questionnaires were lower than
      the general population, individual scores were within the normal range in 78% and
      88% of subjects for the Child Health Questionnaire physical and psychosocial
      summary score, and 97% and 91% for the SF-36 physical and mental aggregate score,
      respectively. Since Fontan surgery, 119 (28%) had additional cardiac surgery; 55%
      of these (n = 66) in the interim between Fontan 1 and Fontan 2. A catheter
      intervention occurred in 242 (57%); 32% of these (n = 78) after Fontan 1.
      Arrhythmia requiring treatment developed in 118 (28%) after Fontan surgery; 58%
      of these (n = 68) since Fontan 1. CONCLUSIONS: We found 95% interim transplant
      free survival for Fontan survivors over an average of 7 years of follow-up.
      Continued longitudinal investigation into adulthood is necessary to better
      understand the determinants of long-term outcomes and to improve functional
      health status.

PMID- 24934525
TI  - [Role of protein disulfide isomerase in activation of integrins].
AB  - Integrins belong to a large family of transmembrane cell adhesion receptors that
      communicate biochemical and mechanical signals in a bidirectional manner across
      the plasma membrane. Integrins and their ligands play a crucial role in a number
      of physiological and pathological processes, including cell migration, cell
      differentiation, hemostasis, adhesion, angiogenesis, cancer, cell invasiveness
      and wound healing. Intracellular signals switch integrins into a ligand-competent
      state as a result of conformational changes within the integrin molecule. Binding
      of extracellular ligands induces structural changes that can transmit signals to
      the cell interior. Transition of integrins from an inactive to a ligand binding
      state involves rearrangement of the disulfide bonding pattern. The rearrangement
      of disulfide bonds is modulated by protein disulfide isomerase (PDI). PDI has
      been found on the surface of several types of cells, including endothelial cells,
      hepatocytes, cancer cells, pancreatic cells and B cells. PDI was identified on
      the platelet surface, where it plays an important role in platelet reactions such
      as adhesion, aggregation and secretion. PDI was found to directly interact with
      integrins. Disulfide-thiol exchange mediated by PDI appears to be involved in the
      conformational changes in integrin activation. In this report we describe the
      structure of integrin and the role of disulfide bond rearrangement in its
      activation. 

PMID- 24934526
TI  - [Mechanisms of urinary tract sterility maintenance].
AB  - Physiologically, urine and the urinary tract are maintained sterile because of
      physical and chemical properties of urine and the innate immune system's action.
      The urinary tract is constantly exposed to the invasion of microorganisms from
      the exterior environment, also because of the anatomical placement of the
      urethra, in the vicinity of the rectum. Particularly vulnerable to urinary tract
      infections (UTI) are women (an additional risk factor is pregnancy), but also the
      elderly and children. The main pathogens causing UTI are bacteria; in 70-95% of
      cases it is the bacterium Escherichia coli. Infections caused by viruses and
      fungi are less common and are associated with decreased immunity,
      pharmacotherapy, or some diseases. Bacteria have evolved a number of factors that
      facilitate the colonization of the urinary tract: the cover and cell membrane
      antigens O and K1, lipopolysaccharide (LPS), fimbriae, pile and cilia. On the
      other hand, the human organism has evolved mechanisms to hinder colonization of
      the urinary tract: mechanisms arising from the anatomical structure of the
      urinary tract, the physicochemical properties of the urine and the activity of
      the innate immune system, also known as non-specific, which isolates and destroys
      pathogens using immunological processes, and the mechanisms for release of
      antimicrobial substances such as Tamm-Horsfall protein, mucopolysaccharides,
      immunoglobulins IgA and IgG, lactoferrin, lipocalin, neutrophils, cytokines and
      antimicrobial peptides. This review aims to analyze the state of knowledge on the
      mechanisms to maintain the sterility of the urinary tract used by the human
      organism and bacterial virulence factors to facilitate the colonization of the
      urinary tract. 

PMID- 24934527
TI  - [The comet assay as a method of identifying chromosomes instability].
AB  - The basic method for analyzing the degree of DNA fragmentation caused by
      genotoxic factors is gel electrophoresis of single cells (single cell gel
      electrophoresis), also called the comet assay. The comet assay enables the
      analysis of the level of several different DNA modifications. The basic testing
      procedure has been only slightly modified. This method helps identify single
      strand and double-strand DNA cracks, as well as any chemical and enzymatic
      modifications that can potentially turn into cracks in DNA or chromatids. The
      comet assay makes it possible to detect DNA damage at the level of single cells.
      It can be employed in analyses of any tissues which provide cellular suspensions.
      Analysed cells are submerged in agarose on a microscope slide. DNA is what is
      left after proteins have been broken down. The slide is then subjected to
      electrophoresis and stained with a fluorescent dye. A "comet-like" image is
      obtained. The "head" is the cell fixation site prior to lysis; the "tail"
      represents damaged DNA fragments. The extent of DNA damage is reflected in the
      length of the tail and the amount of DNA contained in it. The assay finds
      research applications in the following fields: genetic toxicology, monitoring of
      DNA repair following chemotherapy and radiotherapy, ecotoxicology, animal and
      human nourishment, biomonitoring of genotoxicity, epidemiology and assessment of
      material deposited in sperm and blood banks. 

PMID- 24934528
TI  - [Searching for new antibiotics--inhibitors of bacterial chromosome replication].
AB  - The excessive and often unreasonable use of antibacterial drugs leads to rise of
      antibioticresistant strains. To overcome this problem, new antibiotics are
      searched and the new drug targets are investigated. The proteins involved in
      replication of bacterial chromosomes seem to be promising candidates for drug
      targets since they are involved in crucial life pathways and are structurally
      and/or functionally different from the eukaryotic homologues. Within last few
      years, a large number of newly developed methods allowed to search among
      thousands of molecules for the ones that specifically inhibit DNA synthesis in
      the prokaryotic cell. In this review, we present some of these methods. 

PMID- 24934529
TI  - [Yamanaka's factors and core transcription factors--the molecular link between
      embryogenesis and carcinogenesis].
AB  - Oct4 and Sox2 transcription factors (belonging to the Yamanaka's factor family)
      and Nanog, named together as core transcription factors of pluripotency, are
      indispensable to induce and maintain the pluripotency state. They act generally
      as activators of genes coding for transcription factors, cofactors and chromatin
      regulators. They also activate microRNA expression. In addition, Oct4, Sox2 and
      Nanog function as repressors of genes for factors responsible for escape from
      pluripotency and differentiation. Core transcription factors positively regulate
      their own promoters, forming a positive-feedback loop. In recent times,
      researchers' attention has been attracted towards Oct4, Sox2 and Nanog as
      potential markers for cancer stem cells (CSCs). The expression of these factors
      has been confirmed in numerous types of tumors. The aim of this paper is to
      concisely review features of core transcription factors and their role in
      embryogenesis and tumorigenesis including the CSC hypothesis. 

PMID- 24934530
TI  - [Immunoregulatory properties of Hsp70].
AB  - Heat shock proteins 70 (Hsp70) play an important role in maintaining cellular
      homeostasis. As molecular chaperones, Hsp70 are responsible for proper folding of
      newly synthesized polypeptides and refolding of misfolded and aggregated
      proteins. Hsp70 are involved in cellular transport and participate in signal
      transduction processes. The presence of Hsp70 in the extracellular space is
      associated with development of various pathological conditions, including
      autoimmune and cancer diseases. Recent data suggest anti-inflammatory property of
      Hsp70 confirmed in both in vitro and animal models. This paper summarizes recent
      data regarding immunoregulatory properties of Hsp70, and presents promising
      results of the studies concerning the application of heat shock proteins in
      treatment of chronic inflammatory diseases. 

PMID- 24934532
TI  - [Serotonin hypothesis and pulmonary artery hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a progressive, complex disease leading
      to the right ventricular failure and premature death. PAH is characterized by
      increased pulmonary arterial pressure, increased vascular resistance, pulmonary
      vascular remodeling and endothelial dysfunction. Pathomechanism of this disease
      is still unknown. It has been suggested, that endothelial dysfunction is caused
      by unbalance between vasodilators and vasoconstrictors e.g. serotonin (5-HT).
      Previously, serotonin hypothesis was linked to the anorexigens, derivatives of
      fenfluramine, which are serotonin transporter (SERT) substrates. Nowadays, it has
      been proved that all elements of serotonergic system within pulmonary circulation
      participate in the developement of PAH. The tryptophan hydroxylase 1 (Tph-1)
      catalyses synthesis of 5-HT from tryptophan in the pulmonary arterial endothelial
      cells. 5-HT mediates contraction of pulmonary vessels via 5-HT1B and 5-HT2A
      receptors. 5-HT is also transported into pulmonary arterial smooth muscle cells
      via SERT and through activation of reactive oxygen species and Rho-kinase may
      contribute to contraction or/and, via stimulation of transcription factors, lead
      to proliferation and remodelling. There is also increasing number of evidence
      about functional interaction between 5-HT1B receptor and SERT in modulation of
      vasoconstriction and proliferation in pulmonary arteries. This review discusses
      the role of 5-HT in the development of PAH and highlights possible therapeutic
      targets within serotonergic system.

PMID- 24934531
TI  - [The role of selected cytokines and proteins analyzed in bronchoalveolar lavage
      fluid in lung injury].
AB  - The early organism response to injury or infection involves activation of the
      innate immune system, in which pattern recognition receptors (PRRs) participate.
      They recognize highly conservative structures that are called pathogen-associated
      molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The
      interactions between PRRs and PAMPs or DAMPs lead to the activation of
      transcriptional factors which are responsible for gene expression of inflammatory
      mediators and synthesis and release of these factors, and result in the
      development of inflammation. RAGE (receptor for advanced glycation end products)
      and CD163 belonging to PRRs play a significant role in the early immune response
      in lungs. They are expressed on alveolar epithelial cells and alveolar
      macrophages, respectively. NK cells are also involved in lung response to injury,
      though their maturation and the ability to express PRRs depend on the presence of
      IL-15. Detailed knowledge about these factors enables us to understand the signal
      pathways that are activated in the course of infectious and noninfectious lung
      injury. The analysis of these proteins' concentrations in body fluids creates new
      possibilities in monitoring lung injury and predicting the results of treatment.
      In the future, the discussed mediators may become the targets for new forms of
      treatment in life-threatening respiratory diseases. 

PMID- 24934533
TI  - [Pheochromocytoma in pregnancy].
AB  - Pheochromocytoma occurs with a frequency estimated at 2-7 per 100,000 pregnant
      women. Unrecognized, and thus untreated pheochromocytoma is associated with very
      high (40-50%) maternal and fetal mortality. Pheochromocytoma occurs sporadically
      or as a family trait. Its presence should be suspected in women with paroxysmal
      or established hypertension, especially before the 20th week of pregnancy,
      accompanied by headaches and palpitations, and excessive sweating, muscle
      tremors, vomiting, anxiety, vasomotor disturbances and blurred vision. The
      variety of clinical presentations and rarity are the cause of not including the
      disease in differential diagnosis of hypertension in pregnancy. Biochemical tests
      are essential in the diagnosis of pheochromocytoma, and involving the assessment
      of methoxycatecholamine urinary excretion. The second step in the diagnostics is
      magnetic resonance imaging of adrenal glands. Adrenalectomy is the treatment of
      choice for pheochromocytoma with adrenal location, which depends on the timing of
      the tumor diagnosis. Conservative treatment for 10-14 days with pharmacological
      blockade of alpha-adrenergic receptors should precede the surgery. Early
      diagnosis and properly planned treatment of pheochromocytoma significantly
      reduces the risk to the mother and fetus.

PMID- 24934534
TI  - [Molecular diagnosis of food allergy--do we know more?].
AB  - Component-resolved diagnostics (CRD) is the research method that allows to
      determine the concentrations of specific immunoglobulin E against a particular
      allergenic components. The paper discusses the importance of CRD in the food
      allergy diagnosis to common animal and vegetable allergens. The capabilities of
      the method and its limitations in the application are presented. One of the main
      advantages of the CRD is to obtain information on the potential allergen cross
      reactivity regarding inhalant allergens and food, which are exhibiting structural
      similarity within the epitopes. CRD explains on the molecular level allergens
      cross-reactivity. It allows to distinguish cross-reactions occurring after
      ingestion of food in patients with hypersensitivity that occurs primarily to
      pollen from the coexistence of inhaled and food allergies. It is also possible to
      use the method of the CRD for selected allergens to predict the severity of
      allergic reactions after ingestion of allergic food in patients with symptoms of
      food allergy. In addition, in small children component-resolved diagnostics can
      be helpful in predicting achieve in food tolerance to certain allergens. Due to
      the present limitations, practical conclusions and guidance should be drawn with
      a caution. This method does not replace clinical observation and double-blind
      placebo-controlled food challenge, which is still the gold standard in the
      diagnosis of food allergy. Due to the geographic diversity resulting in different
      exposure to pollen and dietary factors researches on allergen components in
      populations living in different climatic zones give different results. This
      allows to observe that the diagnostic and prognostic inference based on the
      analysis of CRD results is limited and should always be considered in the
      clinical context. Especially in situations of estimating the risk of severe
      allergic reactions. Despite these limitations, the CRD method is a modern tool to
      the current diagnosis of allergy deserving of its popularisation. It provides
      information on allergenic components at the molecular level, allowing better
      understanding of symptoms and patient adjusted procedures.

PMID- 24934535
TI  - [Advances in the development of new vaccines against tuberculosis. 100 years
      after the introduction of BCG].
AB  - The BCG vaccine used in the world for nearly 100 years protects children against
      the most severe forms of tuberculosis, but its effectiveness in preventing the
      most commonly occurring tuberculosis and the one burdened with the highest risk
      of transmission in adults is very diverse. Contraindications for BCG vaccination
      include HIV infection and other conditions of immunosuppression. Tuberculosis is
      a global problem difficult to control because of three main reasons: poor
      diagnostics in developing countries, long-term therapy or discontinuation of
      treatment resulting in the emergence of drug-resistant mycobacteria, and the
      availability of a TB vaccine which only protects children from the most severe
      forms of tuberculosis. BCG has little to no efficacy in preventing the most
      common adult pulmonary TB. The development of a more effective vaccine against
      tuberculosis is undoubtedly still a public health priority in order to improve
      control of the disease throughout the world. Elimination of TB as a global public
      health goal by 2050 is particularly ambitious and its achievement depends on the
      development and application of new intervention measures and newly designed
      vaccines. Currently, 14 newly developed products are undergoing clinical trials.
      These include a prophylactic vaccine capable of replacing the current BCG,
      booster vaccines to increase the effects of BCG, and therapeutic vaccines. The
      aim of the study is to present the current state of knowledge on cutting-edge
      research into new vaccines against tuberculosis, their efficacy, immunogenicity
      and potential use in the future. 

PMID- 24934536
TI  - [Molecular actions of 17beta-estradiol and progesterone and their relationship
      with cellular signaling pathways].
AB  - SEX STEROIDS: 17beta-estradiol and progesterone play a major role in modulation
      of reproductive functions of the organism and participate in regulation of a
      broad spectrum of cellular processes in target cells via their specific
      receptors. Our understanding of molecular mechanisms of sex steroid action has
      significantly developed over the last years. Apart from the well-established
      effect of sex steroids on regulation of gene expression, some rapid nongenomic
      mechanisms have been identified, which are involved in modulation of the activity
      of several cellular, membrane-bound and cytoplasmic regulatory proteins. 17beta
      estradiol and progesterone regulate several signal transduction pathways, which
      involve activation of enzymes such as mitogen-activated protein kinases (MAPK),
      phosphatidylinositol 3-kinase and tyrosine kinases. Biological effects of sex
      steroids action constitute a complex interplay of genomic and nongenomic
      mechanisms, and depend on the physiological and genetic context of the target
      cell. Understanding the molecular mechanisms of sex steroids action is therefore
      important and may broaden our knowledge about their role in both physiological
      and pathological processes. This review provides a comprehensive insight into the
      molecular actions of 17beta-estradiol and progesterone, aiming to present the
      role of these sex steroids in regulation of cellular signaling pathways.

PMID- 24934537
TI  - [Cooperation between heat shock proteins in organizing of proteins spatial
      structure].
AB  - Heat shock proteins (Hsps) are a class of proteins with highly conserved amino
      acid sequences. They are widespread in nature; they are found in archeons, true
      bacteria and eukaryotic organisms. Hsps from various families, commonly interact
      to execute essential cellular tasks, such as molecular regulation of newly
      synthesized protein-folding or restoration of the appropriate conformation of
      denatured and aggregated proteins. In this review we discuss mechanisms of
      spatial organization of protein structure mediated by Hsp10, Hsp40, Hsp60, Hsp70,
      Hsp104 (Hsp100) and Hsp110. Interactions between Hsps of different molecular
      weights are described. 

PMID- 24934538
TI  - Comparison of detection methods for extended-spectrum beta-lactamases in
      Escherichia coli strains.
AB  - INTRODUCTION: Detection of extended-spectrum beta-lactamases (ESBLs) could be a
      major challenge for microbiologists--the difficulties arise mainly from the
      phenotypic differences among strains. MATERIALS AND METHODS: Evaluation of ESBLs
      was performed on 42 strains of E. coli by: 1) DDST on MHA, 2) DDST on MHA with
      cloxacillin, 3) CT on MHA, according to CLSI, 4) CT on MHA with cloxacillin, 5)
      Etest ESBL (AB Biodisk), 6) CHROMagarTM ESBL (GRASO), 7) ChromID(r) ESBL
      (bioMerieux), and 8) automatic system VITEK2 ESBL test (bioMerieux). RESULT:
      Positive results were obtained for 20 strains using method 1, for 18 strains
      using method 2, 17 by method 3, 14 by method 4, 11 by method 5, 39 by method 6,
      40 by method 7, and 15 by method 8. Using Etest ESBL 6.0 non-determinable results
      were obtained. The most consistent results were obtained when comparing the
      results of method 3 with results of method 2 (97.6%), and comparing the results
      obtained using methods 3 and 8 (95.2%). CONCLUSIONS: Based on our study we
      conclude that the chromogenic media can only be used as a screening method for
      the detection of ESBLs in E. coli rods. Etest is less useful compared to other
      phenotype methods, due to the impossibility of obtaining results for all the
      tested strains. Adding cloxacillin to MHA does not increase the frequency of
      detection of ESBLs in E. coli strains. DDST seems to be the most reliable among
      phenotypic methods for the detection of ESBLs in E. coli rods.

PMID- 24934539
TI  - [Role of endocannabinoid 2-arachidonoylglycerol in the physiology and
      pathophysiology of the cardiovascular system].
AB  - Cannabinoids, the active ingredients of Cannabis sativa var. indica, have been
      used by humans as recreational and therapeutic agents for thousands of years.
      This group of substances also includes synthetic ligands and, synthesized in the
      body of humans and animals, endocannabinoids. The best known compound classified
      as an endogenous cannabinoid is anandamide. However, recent studies show that
      another compound of this group, 2-arachidonoylglycerol (2-AG), also performs many
      important functions in the organism. 2-Arachidonoylglycerol plays an important
      role in the regulation of the circulatory system via direct and/or indirect,
      through their metabolites, effects on blood vessels and/or heart. Accumulating
      evidence reveals that 2-AG is involved in the pathogenesis of various shocks and
      atherosclerosis. Thus, it may be a novel attractive therapeutic target. However,
      because of rapid metabolism and opposite effects dependent on the experimental
      model, the function of 2-AG still remains to be established. 

PMID- 24934540
TI  - [Alcohol dependence syndrome--symptoms in the oral cavity].
AB  - Alcohol dependence syndrome is defined as a cluster of physiological, behavioural
      and cognitive phenomena in which the use of a psychoactive substance takes on a
      much higher priority for a given individual than other behaviours that once had
      greater value. In European Union the problem of the addiction affects about 5% of
      men and 1% of women each year. Long lasting alcohol abuse is detrimental to the
      whole body, including the oral cavity. The observable changes are usually caused
      by a convergent impact of a number of factors. The changes differ depending on
      the chemical features of the consumed substance, the life style adopted - as a
      consequence of the addiction, simultaneous addiction to nicotine, and finally on
      the medical treatment applied at different stages of the disease. Pathological
      changes may occur in all structures in oral cavity (teeth, periodontium, tongue,
      mucose membrane and salivary glands). Individuals addicted to alcohol revealed
      high percentage of carious losses and chemical damage enamel and dentine and
      inflammatory changes of the periapical area of teeth. Presence of these changes
      is linked unfortunately with low indicator of treatment. There is independence
      between alcohol addiction and damage of periodontium (clinical attachment level
      and pocket depth). Results of alcohol abuse may be also double-sided, painless,
      noninflammatory and non-malignant swelling on salivary glands (sialosis). Alcohol
      is said to be the risk factor for development of flat-epithelial cancer of the
      oral cavity. The most frequent localization of cancerous changes is the bottom of
      the oral cavity and the side of the tongue. 

PMID- 24934542
TI  - Proximity effect in superconductor/conical magnet heterostructures.
AB  - The presence of a spin-flip potential at the interface between a superconductor
      and a ferromagnetic metal allows for the generation of equal-spin spin-triplet
      Cooper pairs. These Cooper pairs are compatible with the exchange interaction
      within the ferromagnetic region and hence allow for the long-range proximity
      effect through a ferromagnet or half-metal. One suitable spin-flip potential is
      provided by incorporating the conical magnet Holmium (Ho) into the interface. The
      conical magnetic structure is characterised by an opening angle alpha with
      respect to the crystal c-axis and a turning (or pitch) angle beta measuring the
      rotation of magnetisation with respect to the adjacent layers. Here, we present
      results showing the influence of conical magnet interface layers with varying
      alpha and beta on the efficiency of the generation of equal-spin spin-triplet
      pairing. The results are obtained by self-consistent solutions of the microscopic
      Bogoliubov-de Gennes equations in the clean limit within a tight-binding model of
      the heterostructure. In particular, the dependence of unequal-spin and equal-spin
      spin-triplet pairing correlations on the conical magnetic angles alpha and beta
      are discussed in detail. 

PMID- 24934543
TI  - Initial diagnoses of patients ultimately diagnosed with prion disease.
AB  - BACKGROUND: Prion diseases are rapidly progressive neurodegenerative diseases
      that frequently mimic other forms of dementia making them difficult to diagnose.
      OBJECTIVE: To explore factors associated with the initial diagnoses of cases
      later determined to be caused by prion disease in an attempt to recognize key
      clinical variables that impact the timely diagnosis of prion disease. METHODS: A
      retrospective chart review performed at Johns Hopkins Medicine and the Department
      of Veterans Affairs Health Care System (1995-2008) was conducted. Ninety-two
      subjects with definite or probable prion disease were included in the analyses.
      Demographic, clinical, diagnostic test results, neuropathologic, molecular, and
      genetic data were collected using a standardized instrument and compared between
      initial diagnosis groups. RESULTS: Cases were separated into five broad
      categories pertaining to their initial diagnoses: prion disease, non-prion
      related dementia, psychiatric disorder, stroke, and other. The majority of cases
      did not receive an initial diagnosis of prion disease (n = 76, 83%). The
      plurality of subjects received an initial diagnosis of a non-prion disease
      related dementia (n = 33, 36%). Mean survival times varied between initial
      diagnosis groups (p = 0.042). Times to cerebrospinal fluid 14-3-3 analysis and
      electroencephalogram also differed between initial diagnosis groups. CONCLUSIONS:
      Most patients with prion disease are initially diagnosed with a non-prion disease
      related dementia. Several clinical features were associated with initial
      diagnoses including survival time, onset of specific symptoms, and times to 14-3
      3 analyses and electroencephalogram. Expanding our knowledge of the various
      clinical presentations of prion disease, especially dementia, may aid in the
      earlier diagnoses of these rapidly progressive diseases.

PMID- 24934541
TI  - Infective endocarditis in Rio de Janeiro, Brazil: a 5-year experience at two
      teaching hospitals.
AB  - INTRODUCTION: Despite the recent advances in diagnosis and treatment, mortality
      rates due to infective endocarditis (IE) remain high if not aggressively treated
      with antibiotics, whether or not associated with surgery. Data on the prevalence,
      epidemiology and etiology of IE from developing countries remain scarce. The aim
      of this observational, prospective cohort study was to report a 5-year experience
      of IE at two teaching hospitals in Rio de Janeiro, Brazil. MATERIAL AND METHODS:
      Demographical, anamnestic and microbiological characteristics of 71 IE patients
      were evaluated during the period of January 2009 to March 2013. RESULTS: The mean
      age of the IE patients was 49.8 +/- 2.4 years, of which 41 (57.7%) were males.
      The median time between the onset of symptoms and diagnosis of IE was 35.8 +/-
      4.8 days. A total of 31 (43.6%) cases of community-acquired infective
      endocarditis (CAIE) and 40 (56.3%) cases of healthcare-acquired infective
      endocarditis (HAIE) were observed. Staphylococcus aureus (30%) was the
      predominant cause of IE. Streptococcus spp. (45.1 %) was the predominant cause of
      the CAIE while S. aureus (32.5%) and Enterococcus spp. (27.2 %) were the main
      etiological agents of HAIE. For 64 (90.1 %) patients with native valve
      endocarditis, the mitral valve was the most commonly affected (48.3%). The main
      source of IE in this cohort was intravascular catheter. The tricuspid valve and
      renal chronic insufficiency were more frequent in patients with HAIE than CAIE (p
      = 0.001). The risk factors associated with in-hospital mortality rate (46.4%) in
      IE patients were: age over 45 (OR 3.4; 95% CI 1.03-11.24; p = 0.04) and chronic
      renal insufficiency (OR 38.3; 95% CI 3.2-449.4; p = 0.004). CONCLUSIONS: At two
      main teaching hospitals in Brazil, Streptococcus spp. was the principal pathogen
      of CAIE while S. aureus and Enterococcus spp. were the most frequent causes of
      HAIE. IE remains a serious disease associated with high in-hospital mortality
      rate (46.6%); especially, in individuals over 45 years of age and with renal
      failure. Data suggest that early surgery may improve the outcome of IE patients.

PMID- 24934544
TI  - Effects of supplementation with omega-3 fatty acids on oxidative stress and
      inflammation in patients with Alzheimer's disease: the OmegAD study.
AB  - BACKGROUND: Oxidative stress and inflammation are two key mechanisms suggested to
      be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids
      (omega-3 FAs) found in fish and fish oil have several biological properties that
      may be beneficial in AD. However, they may also auto-oxidize and induce in vivo
      lipid peroxidation. OBJECTIVE: The objective of this study was to evaluate
      systemic oxidative stress and inflammatory biomarkers following oral
      supplementation of dietary omega-3 FA. METHODS: Forty patients with moderate AD
      were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6
      months. Urinary samples were collected before and after supplementation. The
      levels of the major F2-isoprostane, 8-iso-PGF2alpha, a consistent in vivo
      biomarker of oxidative stress, and 15-keto-dihydro-PGF2alpha, a major metabolite
      of PGF2alpha and biomarker of inflammatory response, were measured. RESULTS: F2
      isoprostane in urine increased in the placebo group after 6 months, but there was
      no clear difference in treatment effect between supplemented and non-supplemented
      patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2alpha.
      At baseline, the levels of 15-keto-dihydro-PGF2alpha showed negative correlative
      relationships to omega-3 FAs, and a positive correlation to linoleic acid. 8-iso
      PGF2alpha correlated negatively to the omega-6 FA arachidonic acid. CONCLUSION:
      The findings indicate that supplementation of omega-3 FAs to patients with AD for
      6 months does not have a clear effect on free radical-mediated formation of F2
      isoprostane or cyclooxygenase-mediated formation of prostaglandin F2alpha. The
      correlative relationships to FAs indicate a potential role of FAs in
      immunoregulation.

PMID- 24934546
TI  - Review of quality deficiencies found in active pharmaceutical ingredient master
      files submitted to the WHO Prequalification of Medicines Programme.
AB  - PURPOSE: The aim of this work was to determine the number and type of active
      pharmaceutical ingredient (API) quality deficiencies in API Master Files (APIMFs)
      as submitted to the World Health Organization (WHO) Prequalification of Medicines
      Programme (PQP). METHODS: We conducted a retrospective review of API quality
      deficiencies identified following the assessment of new APIMFs for non-sterile
      APIs during a 6-year period from 1 January 2007 to 31 December 2012. All
      deficiencies were collected, classified and quantified according to the Common
      Technical Document (CTD) sections and subsections and as groups of commonly
      raised questions. RESULTS: There were 5446 deficiencies collected from 159 APIMF
      deficiency letters by CTD section, by selected CTD subsections and by selected
      CTD subsections and year. More than 50% of the total number of deficiencies
      related to the manufacturing sections of the CTD, followed by deficiencies
      concerning the impurities, the API specification and the stability sections of
      the CTD. A pattern of API deficiencies across the different CTD subsections and
      over time was identified. CONCLUSIONS: The most frequent critical deficiencies
      were related to how the specific manufacturing process and the key materials
      used, in particular the API starting material, impact the API impurities content.
      The number and pattern of APIMF deficiencies did not change over time. The
      results are compared to the findings in similar studies as reported by the United
      States Food and Drug Administration (USFDA), the European Directorate for the
      Quality of Medicines (EDQM) and the European Medicines Agency (EMA) and
      similarities and differences are discussed. Our findings highlight the need for
      greater guidance and technical assistance for API manufacturers submitting APIMFs
      to the PQP.

PMID- 24934545
TI  - Additional clues for a protective role of vitamin D in neurodegenerative
      diseases: 1,25-dihydroxyvitamin D3 triggers an anti-inflammatory response in
      brain pericytes.
AB  - Epidemiological and experimental studies suggest that 1,25-dihydroxyvitamin D3
      (1,25D) plays a neuroprotective role in neurodegenerative diseases including
      Alzheimer's disease. Most of the experimental data regarding the genes regulated
      by this hormone in brain cells have been obtained with neuron and glial cells.
      Pericytes play a critical role in brain function that encompasses their classical
      function in blood-brain barrier control and maintenance. However, the gene
      response of brain pericyte to 1,25D remains to be investigated. Analyses of the
      transcriptomic response of human brain pericytes to 1,25D demonstrate that human
      brain pericytes in culture respond to 1,25D by regulating genes involved in the
      control of neuroinflammation. In addition, pericytes respond to the pro
      inflammatory cytokines tumor necrosis factor-alpha and Interferon-gamma by
      inducing the expression of the CYP27B1 gene which is involved in 1,25D synthesis.
      Taken together, these results suggest that neuroinflammation could trigger the
      synthesis of 1,25D by brain pericytes, which in turn respond to the hormone by a
      global anti-inflammatory response. These findings identify brain pericytes as a
      novel 1,25D-responsive cell type and provide additional evidence for the
      potential value of vitamin D in the prevention or therapy of Alzheimer's disease
      and other neurodegenerative/neuropsychiatric diseases associated with an
      inflammatory component.

PMID- 24934547
TI  - Literature values of terminal half-lives of clozapine are dependent on the time
      of the last data point.
AB  - The pharmacokinetics of clozapine is a subject of intensive research because of
      its narrow therapeutic window and susceptibility to drug-drug interactions. A
      systematic literature search was conducted in PubMed and Google Scholar for half
      life values of clozapine in humans. Twenty-one publications were found to contain
      terminal half-life information of clozapine in humans along with the time of the
      last plasma sample. Average values of the terminal half-lives of clozapine were
      calculated to be 10.2, 13.2, 14.2, 18.3 and 29.2 hours with a last data point at
      12, 24, 48, 72 and 120 hours, respectively. This confirms the notion that one
      would arrive at longer terminal half-lives when longer blood sampling times are
      used in pharmacokinetic studies on clozapine. "Terminal half-lives" of
      therapeutic agent are routinely computed and reported in literature. For drugs
      with a third deep compartment such as clozapine, one should remember to consider
      the time of the last data point when comparing the "terminal" half-life. 

PMID- 24934548
TI  - The risk of recrystallization: changes to the toxicity and morphology of
      pyrimethamine.
AB  - PURPOSE: Pyrimethamine, an anti-malarial agent known to exhibit solid state
      polymorphism, may be purified by means of recrystallization. Recrystallization
      may alter the solid state chemistry of pharmaceuticals, which may impact the
      toxicity and/or manufacturability thereof. We evaluated the risks associated with
      the recrystallization of pyrimethamine. METHODS: Pyrimethamine was recrystallized
      using several organic solvents. X-ray diffraction, thermal analysis, infra-red
      spectroscopy, microscopy, flowability -, solubility and dissolution testing as
      well as computational work were employed to evaluate the recrystallized products.
      RESULTS: A toxic solvatomorph of pyrimethamine (Pyr-MeOH) was found to be the
      product from methanol recrystallization. The elucidation of - and the elaboration
      on the unique characteristics of Pyr-MeOH provides the pharmaceutical industry
      with several means to identify Pyr-MeOH and to distinguish it from the
      pharmaceutically preferred anhydrous form (Pyr). Thermal methods of analysis
      found that the toxicity of Pyr-MeOH may be reversed by overcoming a desolvation
      activation energy of 148 kJ/mol. In addition it was found that recrystallization
      altered the morphology of Pyr. Angle of repose and tapped density determinations
      identified that the different morphologies of Pyr displayed differences in powder
      flow and compressibility behaviour and In Silico calculations were successful in
      rendering morphologies resembling that found experimentally. CONCLUSION: We
      present a solvatomorph of pyrimethamine and provide several characteristic means
      to identify this unwanted toxic form and quantified the energy required to
      overcome its toxicity. In addition we describe that Pyr may present in different
      morphologies and show how it may impact the manufacturability thereof.

PMID- 24934549
TI  - Crushed tablets: does the administration of food vehicles and thickened fluids to
      aid medication swallowing alter drug release?
AB  - PURPOSE: To evaluate the influence of co-administered vehicles on in vitro
      dissolution in simulated gastric fluid of crushed immediate release tablets as an
      indicator for potential drug bioavailability compromise. METHODS: Release and
      dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets
      were tested with six foods and drinks that are frequently used in the clinical
      setting as mixers for crushed medications (water, orange juice, honey, yoghurt,
      strawberry jam and water thickened with Easythick powder) in comparison to whole
      tablets. Five commercial thickening agents (Easythick Advanced, Janbak F,
      Karicare, Nutilis, Viscaid) at three thickness levels were tested for their
      effect on the dissolution of crushed atenolol tablets. RESULTS: Atenolol
      dissolution was unaffected by mixing crushed tablets with thin fluids or food
      mixers in comparison to whole tablets or crushed tablets in water, but amlodipine
      was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets
      with honey, jam or yoghurt caused them to resemble the slow dissolution of whole
      tablets rather than the faster dissolution of crushed tablets in water or orange
      juice. Crushing and mixing any of the four medications with thickened water
      caused a significant delay in dissolution. When tested with atenolol, all types
      of thickening agents at the greatest thickness significantly restricted
      dissolution, and products that are primarily based on xanthan gum also delayed
      dissolution at the intermediate thickness level. CONCLUSIONS: Dissolution
      testing, while simplistic, is a widely used and accepted method for comparing
      drug release from different formulations as an indicator for in vivo
      bioavailability. Thickened fluids have the potential to retard drug dissolution
      when used at the thickest levels. These findings highlight potential clinical
      implications of the addition of these agents to medications for the purpose of
      dose delivery and indicate that further investigation of thickened fluids and
      their potential to influence therapeutic outcomes is warranted.

PMID- 24934550
TI  - Assessing bioequivalence of antiepileptic drugs: are the current requirements too
      permissive?
AB  - PURPOSE: In order to evaluate the permissiveness of current bioequivalence
      requirements for antiepileptic drugs we investigated how accurate Cmax and AUC0-t
      of generic antiepileptic drugs approved in Brazil are in comparison to reference
      products. METHODS: Data collected from assessment reports of approved
      bioequivalence studies archived in the Brazilian regulatory agency in 2007-2012
      were: geometric mean ratios and 90% confidence intervals (CI) for Cmax and AUC0
      t, intra-subject variability (CV) of Cmax and AUC0-t and number of subjects.
      RESULTS: The average difference in Cmax and AUC0-t between generic and reference
      products was 5% and 3%, respectively. Maximum deviation from 1.00 of the CI of
      Cmax can achieve 15-20% (demonstrated in 27% of studies); for AUC0-t, 25% of
      studies showed the deviation can be >10%. All studies that used adequate number
      of subjects for a 90% CI of 0.90-1.11 complied with it for AUC0-t, except one of
      carbamazepine, but only 33% complied with it for both AUC0-t and Cmax. The CV was
      strongly correlated to the maximum CI deviation for AUC0-t (CV of approximately
      15% corresponding to deviation of 10%). Studies that presented maximum CI
      deviation <= 10 % together with CV <= 15% for AUC0-t represented 65% of the
      total. Weaker correlation was observed for Cmax and no correlation was seen
      between maximum CI deviation and number of subjects. CONCLUSIONS: Modification in
      legislation for bioequivalence of antiepileptic drugs is suggested, not only with
      constraint of AUC0-t 90% CI to 0.90-1.11, but also with limitation of the CV to
      15%, as to assure similar variance in pharmacokinetics and diminish the risk of
      critical plasma-level fluctuation when switching between generic and reference
      formulations. Although most generics presented differences <= 10% in AUC0-t
      compared to their references, some narrow therapeutic index drugs displayed
      differences that could be clinically significant after product substitution.

PMID- 24934551
TI  - Anaphylactic reaction to pemetrexed: a case report.
AB  - Pemetrexed is approved to treat non-small cell lung cancer and has an overall
      favorable toxicity profile. We describe a 58-year-old man who developped an
      anaphylactic shock within few minutes from the beginning of pemetrexed perfusion.
      Pemetrexed was discontinued and the patient's symptoms gradually resolved with
      administration of symptomatic treatment. Serum tryptase level remained normal and
      intra dermal skin tests were negative eventhough a nonspecific papule was noted.
      This case suggests that caution should be exercised when prescribing pemetrexed
      and clinicians must be warranted for the possibility of serious adverse events
      associated with pemetrexed use.

PMID- 24934552
TI  - Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery:
      an in vitro investigation on human breast cancer and leukemia cell lines.
AB  - PURPOSE: Histone modification has emerged as a promising approach to cancer
      therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD)
      inhibitor, has shown anticancer activity. Butyrate transcriptional activation is
      indeed able to withdraw cancer cells from the cell cycle, leading to programmed
      cell death. Since butyrate's clinical use is hampered by unfavorable
      pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid
      lipid nanoparticles (SLN), have been developed to overcome these constraints.
      METHODS: In order to outline the influence of butyrate delivery on its anticancer
      activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle
      (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth
      of different human cancer cell lines, such as the promyelocytic leukemia, HL-60,
      and the breast cancer, MCF-7 was investigated. A detailed investigation into the
      mechanism of the induced cytotoxicity was also carried out, with a special focus
      on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by
      real time PCR analysis. RESULTS: In HL-60 cells, CBSLN induced a higher and
      prolonged expression level of the butyrate target genes at lower concentrations
      than NB. This led to a significant decrease in cell proliferation, along with
      considerable apoptosis, cell cycle block in the G0/G1 phase, significant
      inhibition of total HD activity and overexpression of the p21 protein.
      Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the
      butyrate target genes, leading to the same anticancer activity as that of NB.
      CONCLUSIONS: Solid lipid nanoparticles were able to improve butyrate anticancer
      activity in HL-60, but not in MCF-7 cells. This is consistent with difference in
      properties of the cells under study, such as expression of the TP53 tumor
      suppressor, or the transporter for short-chain fatty acids, SLC5A8.

PMID- 24934553
TI  - Random allocation in controlled clinical trials: a review.
AB  - PURPOSE: An allocation strategy that allows for chance placement of participants
      to study groups is crucial to the experimental nature of randomised controlled
      trials. Following decades of the discovery of randomisation considerable
      erroneous opinion and misrepresentations of its concept both in principle and
      practice still exists. In some circles, opinions are also divided on the strength
      and weaknesses of each of the random allocation strategies. This review provides
      an update on various random allocation techniques so as to correct existing
      misconceptions on this all important procedure. METHODS: This is a review of
      literatures published in the Pubmed database on concepts of common allocation
      techniques used in controlled clinical trials. RESULTS: Allocation methods that
      use; case record number, date of birth, date of presentation, haphazard or
      alternating assignment are non-random allocation techniques and should not be
      confused as random methods. Four main random allocation techniques were
      identified. Minimisation procedure though not fully a random technique, however,
      proffers solution to the limitations of stratification at balancing for multiple
      prognostic factors, as the procedure makes treatment groups similar in several
      important features even in small sample trials. CONCLUSIONS: Even though
      generation of allocation sequence by simple randomisation procedure is easily
      facilitated, a major drawback of the technique is that treatment groups can by
      chance end up being dissimilar both in size and composition of prognostic
      factors. More complex allocation techniques that yield more comparable treatment
      groups also have certain drawbacks. However, it is important that whichever
      allocation technique is employed, unpredictability of random assignment should
      not be compromised.

PMID- 24934554
TI  - Antimicrobial and P450 inhibitory properties of common functional foods.
AB  - PURPOSE: To study the effect of functional foods on human cytochrome P450 (CYP)
      and the gut bacterial microflora that may potentially affect drug metabolism and
      ultimately affect human health and wellness. METHODS: This study examined a
      variety of food plants from the Apiaceae, Fabaceae, and Lamiaceae families for
      their inhibitory potential on cytochrome 2D6-, 3A4-, 3A5-, and 3A7-mediated
      metabolism. The antimicrobial effects of these samples were also investigated
      with 7 selected bacterial surrogate species to determine potential effects on the
      gut microflora. RESULTS: The highest CYP inhibitory activities, based upon visual
      examination, were observed from extracts of celery seed, cumin, fennel seed,
      basil, oregano, and rosemary belonging to the Apiaceae and Lamiaceae families,
      respectively. Likewise, the strongest antimicrobial activities were also observed
      in the Apiaceae and Lamiaceae. No significant antimicrobial and CYP inhibition
      was observed in the Fabaceae extracts. CONCLUSION: Results demonstrated the
      possible risk of food-drug interactions from spice and herb plants may affect
      drug disposition and safety.

PMID- 24934555
TI  - Intestinal P-glycoprotein expression is multimodally regulated by intestinal
      ischemia-reperfusion.
AB  - PURPOSE: Reactive oxygen species (ROS) have multiple physiological effects that
      are amount-dependent. ROS are one of the causes of intestinal ischemia
      reperfusion (I/R) injury. In this study, we investigated whether the amount of
      ROS and the degree of intestinal I/R injury affect the expression level of P
      glycoprotein (P-gp). METHODS: . We used hydrogen peroxide (H2O2) as ROS in in
      vitro experiments. Intestinal I/R model rats, which were subjected 15-min
      ischemia (I/R-15), were used in in vivo experiments. RESULTS: P-gp expression in
      Caco-2 cells was increased in response to 1 uM of H2O2 but decreased upon
      exposure to 10 mM of H2O2. We previously reported that P-gp expression is
      decreased after intestinal I/R with 30-min ischemia (I/R-30), which time a large
      amount of ROS is generated. I/R-15 induced slightly less mucosal and oxidative
      injury than did I/R-30. P-gp expression in the jejunum was increased at 1 h after
      I/R-15, and ileal paracellular permeability was increased. The blood
      concentration of tacrolimus, a P-gp substrate, was lower during 0-20 min but was
      higher during 40-90 min post-administration compared with that in the sham
      operated rats. P-gp expression in the ileum was decreased at 6 h after I/R-15,
      due to abnormal localization of P-gp, resulting in a high blood tacrolimus
      concentration in rats reperfused for 6 h. CONCLUSIONS: ROS multimodally regulate
      P-gp expression depending on its amount. This is important for understanding the
      pattern of P-gp expression after intestinal I/R.

PMID- 24934556
TI  - Health care resource utilisation in primary care prior to and after a diagnosis
      of Alzheimer's disease: a retrospective, matched case-control study in the United
      Kingdom.
AB  - BACKGROUND: This study examined medical resource utilisation patterns in the
      United Kingdom (UK) prior to and following Alzheimer's disease (AD) diagnosis.
      METHODS: A patient cohort aged 65 years and older with newly diagnosed AD between
      January 2008 and December 2010 was identified through the UK's Clinical Practice
      Research Datalink (CPRD). Patients with a continuous record in the CPRD (formerly
      the General Practice Research Database [GPRD]) for both the 3 years prior to, and
      the 1 year following, AD diagnosis were eligible for inclusion. A control cohort
      was identified by matching general older adult (GOA) patients to patients with AD
      based on year of birth, gender, region, and Charlson Comorbidity Index at a ratio
      of 2:1. Medical resource utilisation was calculated in 6-month intervals over the
      4-year study period. Comparisons between AD and GOA control cohorts were
      conducted using conditional logistic regression for patient characteristics and a
      generalised linear model for resource utilisation. RESULTS: Data for the AD
      cohort (N = 3,896) and matched GOA control cohort (N = 7,792) were extracted from
      the CPRD. The groups were 65% female and the AD cohort had a mean age of 79.9
      years (standard deviation 6.5 years) at the date of diagnosis. Over the entire
      study period, the AD cohort had a significantly higher mean primary care
      consultation rate than the GOA cohort (p < .0001). While the GOA cohort primary
      care consultation rate gradually increased over the 4-year period (ranging from 5
      to 7 consultations per 6-month period), increases were more pronounced in the AD
      cohort (ranging from 6 to 11 consultations per 6-month period, peaking during the
      6-month periods immediately prior to and post diagnosis). The AD cohort also had
      a higher overall specialty referral rate than the GOA cohort over the 4-year
      period (37% vs. 25%, respectively; p < .0001); the largest difference was during
      the 6 months immediately prior to AD diagnosis (17% vs. 5%, respectively; p <
      .0001). CONCLUSIONS: In the UK, AD diagnosis is associated with significant
      increases in primary and secondary care resource utilisation, continuing beyond
      diagnosis. This evidence may be important to health care commissioners to
      facilitate effective mobilisation of appropriate AD-related health care
      resources.

PMID- 24934557
TI  - Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology
      for amphibians.
AB  - Amphibian populations are declining worldwide, particularly in tropical regions
      where amphibian diversity is highest. Pollutants, including agricultural
      pesticides, have been identified as a potential contributor to decline, yet
      toxicological studies of tropical amphibians are very rare. The present study
      assesses toxic effects on amphibians of 10 commonly used commercial pesticides in
      tropical agriculture using 2 approaches. First, the authors conducted 8-d
      toxicity assays with formulations of each pesticide using individually reared red
      eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review
      of available data for the lethal concentration to kill 50% of test animals from
      the US Environmental Protection Agency's ECOTOX database to allow comparison with
      their findings. Lethal concentration estimates from the assays ranged over
      several orders of magnitude. The nematicides terbufos and ethoprophos and the
      fungicide chlorothalonil were very highly toxic, with evident effects within an
      order of magnitude of environmental concentrations. Acute toxicity assays and
      meta-analysis show that nematicides and fungicides are generally more toxic than
      herbicides yet receive far less research attention than less toxic herbicides.
      Given that the tropics have a high diversity of amphibians, the findings
      emphasize the need for research into the effects of commonly used pesticides in
      tropical countries and should help guide future ecotoxicological research in
      tropical regions.

PMID- 24934560
TI  - Porous nitrogen-doped carbon microspheres as anode materials for lithium ion
      batteries.
AB  - Nitrogen-doped carbon microspheres (NCSs) were fabricated via a simple, fast and
      energy-saving microwave-assisted method followed by thermal treatment under an
      ammonia atmosphere. NCSs thermally treated at different temperatures were
      investigated as anode materials for lithium ion batteries (LIBs). The results
      show that NCSs treated at 900  degrees C exhibit a maximum reversible capacity of
      816 mA h g(-1) at a current density of 50 mA g(-1) and preserve a capacity of 660
      mA h g(-1) after 50 cycles, and even at a high current density of 1000 mA g(-1),
      a capacity of 255 mA h g(-1) is maintained. The excellent electrochemical
      performance of NCSs is due to their porous structure and nitrogen-doping. The
      present NCSs should be promising low-cost anode materials with a high capacity
      and good cycle stability for LIBs. 

PMID- 24934559
TI  - Mannosylation of fungal glycoconjugates in the Golgi apparatus.
AB  - Glycosylation is a crucial step in the modification of proteins or sphingolipids
      that then play a prominent role in fungal biology. Glycosylation controls the
      structure and plasticity of the fungal cell wall and fungi-host interactions. Non
      pathogenic and pathogenic yeasts, such as Saccharomyces cerevisiae and Candida
      albicans, respectively, have been useful models for analyzing the mannosylation
      of proteins and sphingolipids, which mainly takes place in the Golgi apparatus.
      Studies of these yeasts have identified different mannosyltransferases that
      belong to separate families of glycosyltransferases. The characterization of
      mannosyltransferases and their activities is essential for deciphering cell wall
      biogenesis, for identifying mannosides involved in virulence and for designing
      inhibitors that target specific mannosylation processes. 

PMID- 24934561
TI  - Between a fifth and a third of hospitals record inaccurate cost data.

PMID- 24934558
TI  - Transcript maturation in apicomplexan parasites.
AB  - The complex life cycles of apicomplexan parasites are associated with dynamic
      changes of protein repertoire. In Toxoplasma gondii, global analysis of gene
      expression demonstrates that dynamic changes in mRNA levels unfold in a serial
      cascade during asexual replication and up to 50% of encoded genes are unequally
      expressed in development. Recent studies indicate transcription and mRNA
      processing have important roles in fulfilling the 'just-in-time' delivery of
      proteins to parasite growth and development. The prominence of post
      transcriptional mechanisms in the Apicomplexa was demonstrated by mechanistic
      studies of the critical RNA-binding proteins and regulatory kinases. However, it
      is still early in our understanding of how transcription and post-transcriptional
      mechanisms are balanced to produce adequate numbers of specialized forms that is
      required to complete the parasite life cycle. 

PMID- 24934563
TI  - Isolation of Leptospira interrogans Hardjoprajitno from vaginal fluid of a
      clinically healthy ewe suggests potential for venereal transmission.
AB  - A total of 15 adult ewes from one flock known to be seroreactive for
      leptospirosis was studied. Urine and vaginal fluid were collected from each
      animal to test for the presence of leptospires using bacterial culture and
      conventional PCR methods. One pure culture of Leptospira sp. was obtained from
      the vaginal fluid sample of a non-pregnant ewe. The isolate was characterized by
      DNA sequencing of the rrs and secY genes, variable-number of tandem-repeats
      (VNTR) analysis and serogrouping, and the isolate was typed as Leptospira
      interrogans serogroup Sejroe serovar Hardjo type Hardjoprajitno. This report
      indicates the presence of viable Leptospira in the vaginal fluid of a ewe,
      suggesting the potential for venereal transmission of leptospires in sheep. 

PMID- 24934562
TI  - Efficient design of meganucleases using a machine learning approach.
AB  - BACKGROUND: Meganucleases are important tools for genome engineering, providing
      an efficient way to generate DNA double-strand breaks at specific loci of
      interest. Numerous experimental efforts, ranging from in vivo selection to in
      silico modeling, have been made to re-engineer meganucleases to target relevant
      DNA sequences. RESULTS: Here we present a novel in silico method for designing
      custom meganucleases that is based on the use of a machine learning approach. We
      compared it with existing in silico physical models and high-throughput
      experimental screening. The machine learning model was used to successfully
      predict active meganucleases for 53 new DNA targets. CONCLUSIONS: This new method
      shows competitive performance compared with state-of-the-art in silico physical
      models, with up to a fourfold increase in terms of the design success rate.
      Compared to experimental high-throughput screening methods, it reduces the number
      of screening experiments needed by a factor of more than 100 without affecting
      final performance.

PMID- 24934564
TI  - Reactivity and survivability of glycolaldehyde in simulated meteorite impact
      experiments.
AB  - Sugars of extraterrestrial origin have been observed in the interstellar medium
      (ISM), in at least one comet spectrum, and in several carbonaceous chondritic
      meteorites that have been recovered from the surface of the Earth. The origins of
      these sugars within the meteorites have been debated. To explore the possibility
      that sugars could be generated during shock events, this paper reports on the
      results of the first laboratory impact experiments wherein glycolaldehyde, found
      in the ISM, as well as glycolaldehyde mixed with montmorillonite clay, have been
      subjected to reverberated shocks from ~5 to >25 GPa. New biologically relevant
      molecules, including threose, erythrose and ethylene glycol, were identified in
      the resulting samples. These results show that sugar molecules can not only
      survive but also become more complex during impact delivery to planetary bodies. 

PMID- 24934565
TI  - Knowledge translation strategies for enhancing nurses' evidence-informed decision
      making: a scoping review.
AB  - BACKGROUND: Nurses are increasingly expected to engage in evidence-informed
      decision making (EIDM); the use of research evidence with information about
      patient preferences, clinical context and resources, and their clinical expertise
      in decision making. Strategies for enhancing EIDM have been synthesized in high
      quality systematic reviews, yet most relate to physicians or mixed disciplines.
      Existing reviews, specific to nursing, have not captured a broad range of
      strategies for promoting the knowledge and skills for EIDM, patient outcomes as a
      result of EIDM, or contextual information for why these strategies "work." AIM:
      To conduct a scoping review to identify and map the literature related to
      strategies implemented among nurses in tertiary care for promoting EIDM
      knowledge, skills, and behaviours, as well as patient outcomes and contextual
      implementation details. METHODS: A search strategy was developed and executed to
      identify relevant research evidence. Participants included registered nurses,
      clinical nurse specialists, nurse practitioners, and advanced practice nurses.
      Strategies were those enhancing nurses' EIDM knowledge, skills, or behaviours, as
      well as patient outcomes. Relevant studies included systematic reviews,
      randomized controlled trials, cluster randomized controlled trials, non
      randomized trials (including controlled before and after studies), cluster non
      randomized trials, interrupted time series designs, prospective cohort studies,
      mixed-method studies, and qualitative studies. Two reviewers performed study
      selection and data extraction using standardized forms. Disagreements were
      resolved through discussion or third party adjudication. RESULTS: Using a
      narrative synthesis, the body of research was mapped by design, clinical areas,
      strategies, and provider and patient outcomes to determine areas appropriate for
      a systematic review. CONCLUSIONS: There are a sufficiently high number of studies
      to conduct a more focused systematic review by care settings, study design,
      implementation strategies, or outcomes. A focused review could assist in
      determining which strategies can be recommended for enhancing EIDM knowledge,
      skills, and behaviours among nurses in tertiary care.

PMID- 24934566
TI  - Results of a Culturally Adapted Internet-Enhanced Physical Activity Pilot
      Intervention for Overweight and Obese Young Adult African American Women.
AB  - PURPOSE: This study evaluated a culturally relevant, social cognitive theory
      based, Internet-enhanced physical activity (PA) pilot intervention developed for
      overweight/obese African American (AA) female college students. DESIGN: Using a 3
      month, single group, pretest-posttest design, participants accessed a culturally
      relevant PA promotion website and engaged in four moderate-intensity PA sessions
      each week. RESULTS: Study completers (n = 25, mean age = 21.9 years) reported a
      decrease in sedentary screen time (p < .0001); however, no changes in moderate-to
      vigorous PA were reported (p = .150). A significant increase in self-regulation
      for PA (p < .0001) and marginally significant increases in social support (p =
      .052) and outcome expectations (p = .057) for PA were observed. No changes in
      body mass index (p = .162), PA enjoyment (p = .151), or exercise self-efficacy (p
      = .086) were reported. CONCLUSIONS: Findings of this exploratory study show some
      preliminary support for Internet-enhanced approaches to promote PA among
      overweight/obese AA women. IMPLICATIONS FOR PRACTICE: Future studies with larger
      samples are needed to further explore culturally relevant Internet-enhanced PA
      programs in this underserved population.

PMID- 24934567
TI  - Bidirectional influences of anxiety and depression in young children.
AB  - Anxiety and depression tend to co-occur in children. Studies indicate that higher
      levels of anxiety are associated with subsequent higher levels of depression,
      while depression may inhibit subsequent anxiety. It is important to increase our
      understanding of the temporal sequencing of these disorders and, particularly, to
      determine if suppression effects account for the inhibitory association. In
      addition, further information about these relationships in young children is
      needed. Participants were a diverse (20.4 % Hispanic, 16.7 % African American;
      49.1 % boys) community sample of 796 children with data available at ages 4, 5,
      and 6-7 years. Anxiety and depression symptoms were assessed using the Child
      Symptom Inventory and symptom count measures from the Diagnostic Interview
      Schedule for Children-Parent Scale -Young Child version. The results indicated:
      (a) anxiety and depression were relatively stable over time; (b) anxiety at age 4
      and 5 was a significant positive predictor of subsequent depression; (c) while an
      inhibitory effect of depression on subsequent anxiety was found, that inhibitory
      effect was due to negative suppression, and higher levels of depression were
      actually associated with subsequent anxiety; (e) consistent with a significant
      suppression effect, when depression was included as a predictor, the association
      between anxiety at ages 4 and 5 and anxiety one year later increases in
      magnitude. Both anxiety and depression are associated with higher levels of one
      another in the subsequent year. Implications for prevention are discussed. 

PMID- 24934568
TI  - A longitudinal moderated mediation model of nonsuicidal self-injury among
      adolescents.
AB  - This study tested a longitudinal moderated mediation model of the engagement in
      non suicidal self-injury (NSSI) based on Nock's (2009) integrated theoretical
      model of the development of NSSI. We assessed general predisposing factors (i.e.
      borderline personality disorder features), precipitating factors (i.e. negative
      emotions), and NSSI-specific vulnerability factors (i.e. behavioral impulsivity
      and self-criticism) among 3,600 Chinese secondary school adolescents (56.6 %
      females, aged between 12 and 18 years). Assessments were conducted for three
      times, 6 months apart. Results supported the longitudinal mediation model, such
      that negative emotions mediated the relation of borderline personality disorder
      features to NSSI. The moderating effects of behavioral impulsivity and self
      criticism were both significant, indicating that adolescents with higher levels
      of both variables were more likely to engage in NSSI. Moreover, behavioral
      impulsivity made additional contribution to the prediction of future NSSI above
      and beyond the effects of other risk factors. Findings of this study may help to
      elucidate the diverse roles of different types of risk factors in the engagement
      in NSSI, and may also shed new light on our understanding about the nature of
      this behavior.

PMID- 24934570
TI  - Narcissism and other-derogation in the absence of ego threat.
AB  - The relation between narcissism and other-derogation has been examined primarily
      in the context of ego threat. In three studies, we investigated whether
      narcissistic individuals derogate others in the absence of ego threat. In Study
      1, 79 judges watched four videotaped dyadic interactions and rated the
      personality of the same four people. In Study 2, 66 judges rated the personality
      of a friend. In Study 3, 72 judges considered the average Northeastern University
      student and rated the personality of this hypothetical person. Across the three
      studies, targets' personality characteristics were described on the 100-item
      California Adult Q-Sort (CAQ; Block, 2008). Judges' ratings of targets were
      compared to a CAQ prototype of the optimally adjusted person to assess target
      derogation. Judges' narcissism and other-derogation were positively related in
      Studies 1 and 2. Narcissism positively predicted and self-esteem negatively
      predicted target-derogation after controlling for each other in Study 3.
      Narcissistic individuals derogate others more than non-narcissistic individuals
      regardless of whether ego threat is present or absent. 

PMID- 24934569
TI  - Identification of novel craniofacial regulatory domains located far upstream of
      SOX9 and disrupted in Pierre Robin sequence.
AB  - Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a
      disorder of skeletal development associated with 46,XY disorders of sex
      development (DSDs). Translocations, deletions, and duplications within a ~2 Mb
      region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially,
      suggesting the existence of an unusually large cis-regulatory control region.
      Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an
      endophenotype of CD and a locus for isolated PRS at ~1.2-1.5 Mb upstream of SOX9
      has been previously reported. The craniofacial regulatory potential within this
      locus, and within the greater genomic domain surrounding SOX9, remains poorly
      defined. We report two novel deletions upstream of SOX9 in families with PRS,
      allowing refinement of the regions harboring candidate craniofacial regulatory
      elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial
      tissue led to the identification of several novel craniofacial enhancers at the
      SOX9 locus, which were validated in transgenic reporter mice and zebrafish.
      Notably, some of the functionally validated elements fall within the PRS
      deletions. These studies suggest that multiple noncoding elements contribute to
      the craniofacial regulation of SOX9 expression, and that their disruption results
      in PRS. 

PMID- 24934571
TI  - Diphenylpyrroles: Novel p53 activators.
AB  - Cellular tumor antigen p53 is crucial for cancer prevention via different
      mechanisms. E3 ubiquitin-protein ligase HDM2 binds to p53, blocks its ability to
      activate transcription, and therefore acts as a negative regulator. Blocking p53
      binding site on HDM2 was believed to generate efficient antitumor agents. So far,
      limited scaffolds were reported with HDM2 antagonist activity. Herein,
      diphenylpyrroles were introduced and evaluated as a novel scaffold in the field
      of p53 activators. An efficient synthesis of novel 3-heteroaryl-pyrroles is
      described via reactions of E-3-(dimethylamino)-1-(2-methyl-4,5-diphenyl-1H-pyrrol
      3-yl)prop-2-en-1-one or E-1-(2-methyl-4,5-diphenyl-1H-pyrrol-3-yl)-3
      morpholinoprop-2-en-1-one with hydrazine hydrate, phenyl hydrazine,
      hydroxylamine, various heterocyclic amines and active methylene compounds. 

PMID- 24934572
TI  - Synthesis, antibacterial and antitubercular activities of benzimidazole bearing
      substituted 2-pyridone motifs.
AB  - A series of benzimidazole bearing 2-pyridones 5a-r were synthesized and evaluated
      for their in vitro antibacterial and antitubercular activity. Further, all
      compounds were examined for their cytotoxic study on VERO cell line and
      characterized by well-known spectral techniques. It was observed that the
      compounds 5h, 5i, 5k, 5q and 5r were found to possess significant broad spectrum
      antibacterial activity (12.5-100 MUg/mL of MIC), while compounds 5g-5i, 5k and 5l
      proved to be the most potent antitubercular activity in range of 2.76-20.4 MUM of
      MIC at low level of cytotoxicity, indicating good selectivity. From SAR studies,
      lipophilic profile of compounds was remarkably vital for antibacterial activity,
      while MIC values of antitubercular activity could not be directly correlated with
      lipophilicity.

PMID- 24934573
TI  - Design, synthesis and antifungal activity of novel triazole derivatives
      containing substituted 1,2,3-triazole-piperdine side chains.
AB  - Due to increasing incidence of invasive fungal infections and severe drug
      resistance to triazole antifungal agents, a series of novel antifungal triazoles
      with substituted triazole-piperidine side chains were designed and synthesized.
      Most of the target compounds showed good inhibitory activity against a variety of
      clinically important fungal pathogens. In particular, compounds 8t and 8v were
      highly active against Candida albicans and Cryptococcus neoformans with MIC
      values in the range of 0.125 MUg/mL to 0.0125 MUg/mL. They represent promising
      leads for the development of new generation of triazole antifungal agents.
      Molecular docking studies revealed that the target compounds interacted with
      CACYP51 mainly through hydrophobic and Van der Waals interactions.

PMID- 24934575
TI  - Toll-like receptor 3 inhibits Newcastle disease virus replication through
      activation of pro-inflammatory cytokines and the type-1 interferon pathway.
AB  - Newcastle disease virus (NDV) is an avian paramyxovirus that can selectively
      replicate in and destroy human tumor cells. In this report, we demonstrate that
      NDV infection in HeLa cells leads to the activation of the pattern recognition
      Toll-like receptor 3 (TLR3). Overexpression of TLR3 enhanced the activity of the
      IFN-beta promoter and the transcription factor NF-kappa B (NF-kappaB), thereby
      decreasing viral protein synthesis and the virus titer. In addition, the
      reduction of endogenous TLR3 by small interfering RNA (siRNA) increased NDV
      replication. Similar anti-NDV effects were observed in DF-1 chicken fibroblast
      cells with the exogenous expression of chicken TLR3 (cTLR3). Immunofluorescence
      staining of HeLa cells indicated that the dsRNA generated during NDV replication
      colocalized with TLR3 in punctate subcellular structures. Altogether, our results
      strongly suggest that TLR3 actively participates in the recognition of the innate
      pro-inflammatory response after NDV infection and leads to the consequent
      antiviral cytokine/interferon secretion. 

PMID- 24934576
TI  - Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor
      2 from a malignant renal solitary fibrous tumor - clinical case and literature
      review.
AB  - BACKGROUND: Hypoglycemic episodes are infrequent in individuals without a history
      of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such
      individuals, an uncommon but important diagnosis to consider is non-islet cell
      tumor hypoglycemia (NICTH). We report a case of NICTH associated with
      paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current
      relevant medical literature. CASE PRESENTATION: A 60 year old male with no
      relevant past medical history was referred to the endocrinology clinic with 18
      month history of episodic hypoglycemic symptoms and, on one occasion was noted to
      have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia.
      Basic laboratory evaluation was unrevealing. Further evaluation however showed an
      elevated serum IGF-2 level at 2215 ng/mL (reference range 411-1248 ng/mL).
      Imaging demonstrated a large right suprarenal mass. A right nephrectomy with
      resection of the mass demonstrated a malignant solitary fibrous tumor. Post
      resection, the patient's IGF-2 levels normalized and hypoglycemic symptoms
      resolved. CONCLUSION: Due to the structural and biochemical homology between IGF
      2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A
      posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic
      activity. Review of recent reported cases of NICTH identified widespread anatomic
      locations and varied pathologic diagnoses of tumors associated with
      paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of
      hypoglycemia associated with paraneoplastic production of IGF-2 consists of
      resection of the tumor responsible for IGF-2 production. Accumulating literature
      provides a firm basis for routine IGF-2 laboratory evaluation in patients
      presenting with spontaneous hypoglycemia with no readily apparent cause.

PMID- 24934578
TI  - Psychometric properties of the finding a balance scale for family caregivers of
      elders with dementia in Taiwan.
AB  - The Finding a Balance Scale, designed to measure the degree to which caregivers
      can balance the competing demands of caregiving and other priorities, assists
      health care providers in understanding the process of family caregiving. The aim
      of this study was to examine the scale's psychometric properties and determine an
      appropriate cutoff score for identifying caregivers at high risk for poor
      caregiving consequences. We found adequate reliabilities and appropriate
      validities in a convenience sample of 197 family caregivers of elders with
      dementia in Taiwan. The optimal cutoff was also determined. The validated Finding
      a Balance Scale provides an assessment tool to explore the competing
      responsibilities, conditions, and difficulties for family caregivers of elders
      with dementia in Taiwan.

PMID- 24934577
TI  - Significance of 18 F-FDG PET and immunohistochemical GLUT-1 expression for
      cardiac myxoma.
AB  - Cardiac tumours are relatively rare and are difficult to diagnose merely with
      imaging techniques. We demonstrated an unusual case of left atrial myxoma,
      displaying the successful detection by positron emission tomography using 2-deoxy
      2-[18 F] fluoro-D-glucose (18 F-FDG PET), correlated closely to more intense and
      enhanced immunoreactivity with glucose transporter-1 (GLUT-1) in a substantial
      number of cardiac myxoma cells. Further prospective studies are needed to
      validate the significance of 18 F-FDG PET findings for cardiac myxoma and the
      association with immunohistochemical GLUT-1 expression in its tumour cells, after
      collecting and investigating a larger number of surgical cases examined with both
      of them. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2991481941253449.

PMID- 24934579
TI  - Plasticity and redundancy among AMA-RON pairs ensure host cell entry of
      Toxoplasma parasites.
AB  - Malaria and toxoplasmosis are infectious diseases caused by the apicomplexan
      parasites Plasmodium and Toxoplasma gondii, respectively. These parasites have
      developed an invasion mechanism involving the formation of a moving junction (MJ)
      that anchors the parasite to the host cell and forms a ring through which the
      parasite penetrates. The composition and the assembly of the MJ, and in
      particular the presence of protein AMA1 and its interaction with protein RON2 at
      the MJ, have been the subject of intense controversy. Here, using reverse
      genetics, we show that AMA1, a vaccine candidate, interacts with RON2 to maintain
      the MJ structural integrity in T. gondii and is subsequently required for
      parasite internalization. Moreover, we show that disruption of the AMA1 gene
      results in upregulation of AMA1 and RON2 homologues that cooperate to support
      residual invasion. Our study highlights a considerable complexity and molecular
      plasticity in the architecture of the MJ. 

PMID- 24934580
TI  - Postsurgical Pantoea calida meningitis: a case report.
AB  - INTRODUCTION: Pantoea calida, a recently described environmental
      Enterobacteriaceae organism, has not yet been associated with human infection.
      CASE PRESENTATION: We report a case of postoperative meningitis caused by P.
      calida. After pituitary adenoma resection, a 52-year-old Caucasian woman
      developed febrile meningitis confirmed by cerebrospinal fluid analysis. P. calida
      was grown in pure culture from this fluid and was firmly identified with partial
      rpoB gene sequencing. She was cured by a 14-day course of meropenem. CONCLUSIONS:
      P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens
      responsible for postsurgical meningitis. It is easily identified by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.

PMID- 24934581
TI  - Towards rapid genotyping of resistant malaria parasites: could loop-mediated
      isothermal amplification be the solution?
AB  - Loop-mediated isothermal amplification (LAMP) is an innovative molecular
      technique that has been validated for point-of-care testing to diagnose malaria.
      Molecular detection and tracking of anti-malarial drug resistance is mainly based
      on highly sophisticated, costly and time-consuming techniques. With the
      validation of resistance-associated gene mutations in malaria parasites, there is
      a need to develop rapid, easy-to-use molecular tests for anti-malarial drug
      resistance genotyping. LAMP could be further developed as a point-of-care test to
      rapidly detect anti-malarial drug resistance-associated molecular markers,
      thereby help detecting and monitoring drug resistance in surveillance studies. 

PMID- 24934582
TI  - High volumetric breast density predicts risk for breast cancer in postmenopausal,
      but not premenopausal, Korean Women.
AB  - PURPOSE: We investigated the association between mammographic breast density and
      breast cancer risk in Korean women according to menopausal status and breast
      cancer subtypes. METHODS: We enrolled 677 patients diagnosed with breast cancer
      and 1,307 healthy controls who participated in screening mammography at the
      National Cancer Center. Breast density was estimated using volumetric breast
      composition measurement. RESULTS: Of the total population, 1,156 (58.3 %) women
      were postmenopausal. The risk of breast cancer increased progressively with the
      increment of volumetric density grade (VDG) in postmenopausal women (p < 0.001).
      High breast density (VDG 4) was significantly associated with breast cancer
      compared with low breast density (VDG 1/2) regardless of body mass index.
      However, the association with parity and history of hormone replacement therapy
      (HRT) was only found in those with >=2 children and those not receiving HRT.
      Breast density was positively associated with breast cancer risk regardless of
      histologic grade, tumor size, lymph node involvement, Ki67 index, and hormone
      receptor status. The association was more prominent in human epidermal growth
      factor receptor 2 (HER2)-positive tumors (VDG 1/2 vs. VDG 4 for HER2 normal, odds
      ratio [OR] 2.21, 95 % confidence interval [CI] 1.28-3.83, p < 0.001; for HER2
      positive, OR 8.63, 95 % CI 3.26-22.83, p = 0.001; P heterogeneity = 0.030).
      However, no significant association was found between breast density and breast
      cancer risk in premenopausal women except for those with large-sized tumors (>2
      cm) and a Ki67 index >15 %. CONCLUSION: High volumetric breast density is
      significantly associated with the risk of breast cancer in postmenopausal women;
      however, these relationships were not found in premenopausal women.

PMID- 24934583
TI  - CT-guided high-dose-rate brachytherapy of liver tumours does not impair hepatic
      function and shows high overall safety and favourable survival rates.
AB  - BACKGROUND OR PURPOSE: Computed tomography-guided high-dose-rate brachytherapy
      (CT-HDRBT) is an emerging therapeutic option for irresectable liver tumours.
      However, its potentially negative effect on liver function has not yet been
      investigated. The aim of this study was to evaluate CT-HDRBT for potential liver
      damage and functional impairment by means of quantitative liver function tests,
      patient safety, and survival. METHODS: Sixty-nine patients receiving hepatic CT
      HDRBT were investigated in a prospective study. The liver function was determined
      before and after intervention, and 6 and 12 weeks later. The study visits
      included liver function assessment by conventional biochemical parameters, the
      liver function capacity test based on 13C-Methacetin (MA) kinetics in ug/kg/hr
      (LiMAx test), and the indocyanine green plasma disappearance rate test. Tumour
      progression was re-staged by magnetic resonance imaging (MRI) twice. The 2-year
      survival was analysed. RESULTS: A significant alteration of biochemical liver
      parameters was observed for liver enzymes and bilirubin directly after
      intervention, all biochemical parameters had normalised at the 6-week follow-up.
      There were no changes in LiMAx test values after the intervention, showing no
      effect on metabolic liver function capacity. In approximately two-thirds of the
      patients, MRI re-staging revealed a significant tumour response, and no local
      tumour recurrence occurred. No patient developed a radiation-induced liver
      disease. CONCLUSION: CT-HDRBT for local tumour treatment has little impact on
      total liver function capacity by high patient safety and encouraging survival
      rates. Thus, it should be an important option in treating patients without a
      surgical alternative, especially when liver function is impaired due to previous
      surgery or chronic liver disease.

PMID- 24934584
TI  - Robotic thyroidectomy for cancer in the US: patterns of use and short-term
      outcomes.
AB  - BACKGROUND: We describe nationally representative patterns of utilization and
      short-term outcomes from robotic versus open thyroidectomy for thyroid cancer.
      METHODS: Descriptive statistics and multivariable analysis were used to analyze
      patterns of use of robotic thyroidectomy from the National Cancer Database (2010
      2011). Short-term outcomes were compared between patients undergoing robotic
      versus open thyroidectomy, while adjusting for confounders. RESULTS: A total of
      68,393 patients with thyroid cancer underwent thyroidectomy; 225 had robotic
      surgery and 57,729 underwent open surgery. Robotic thyroid surgery use increased
      by 30 % from 2010 to 2011 (p = 0.08). Robotic cases were reported from 93
      centers, with 89 centers performing <10 robotic cases. Compared with the open
      group, the robotic group was younger (51 vs. 47 years; p < 0.01) and included
      more Asian patients (4 vs. 8 %; p = 0.006) and privately-insured patients (68 vs.
      77 %; p = 0.01). Tumor size was similar between patients undergoing robotic
      versus open surgery. Total thyroidectomy was performed less frequently in the
      robotic group (67 vs. 84 % open; p < 0.0001). Patients were relatively more
      likely to undergo robotic surgery if they were female (odds ratio [OR] 1.6; p =
      0.04), younger (OR 0.8/10 years; p < 0.0001), or underwent lobectomy (OR 2.4; p <
      0.0001). In adjusted multivariable analysis, there were no differences in the
      number of lymph nodes removed or length of stay between groups; however, there
      was a non-significant increase in the incidence of positive margins with robotic
      thyroidectomy. CONCLUSIONS: Use of robotic thyroidectomy for thyroid cancer is
      limited to a few institutions, with short-term outcomes that are comparable to
      open surgery. Multi-institutional studies should be undertaken to compare
      thyroidectomy-specific complications and long-term outcomes.

PMID- 24934586
TI  - The promise of axillary imaging in individualized surgical management of breast
      cancer patients: another step forward.

PMID- 24934585
TI  - Rate of contralateral prophylactic mastectomy is influenced by preoperative MRI
      recommendations.
AB  - BACKGROUND: Women with breast cancer increasingly undergo contralateral
      prophylactic mastectomy (CPM). We evaluated the relationship between preoperative
      magnetic resonance imaging (MRI) findings and CPM. Other clinicopathologic
      variables associated with CPM choice and the pathology found in the contralateral
      breast are also reported. METHODS: Newly diagnosed breast cancer patients were
      prospectively enrolled in the University of Iowa Breast Molecular Epidemiology
      Resource. Patients with stages 0-III breast cancer who underwent mastectomy for
      the index cancer were eligible for this analysis. Univariate logistic regression
      and a multivariate model were used to identify factors predictive of CPM.
      RESULTS: Among 134 patients (mean age 54.9 years), 53 (39.6 %) chose CPM. On
      univariate analysis, patients undergoing CPM were more likely to have a
      preoperative breast MRI (64.2 vs. 39.5 %, p = 0.006) and to have follow-up
      testing recommended for the contralateral breast (28.3 vs. 4.9 %, p = 0.001).
      Univariate analysis also associated CPM with younger age (p < 0.0001), BRCA
      testing (p < 0.0001), BRCA mutation (p = 0.034) and reconstruction performed (p =
      0.001). Median age of youngest child at diagnosis varied significantly between
      the CPM (15.9 years) and non-CPM (24.3 years) groups (p = 0.0018). On
      multivariate analysis, MRI follow-up recommendation, young age, reconstruction
      and human epidermal growth factor receptor 2 (HER2) positivity of the index
      cancer were significantly associated with CPM. Of the CPM specimens, one (1.8 %)
      had ductal carcinoma-in situ, which had not been identified on MRI. CONCLUSIONS:
      Abnormal findings in the contralateral breast on preoperative MRI, as well as
      young age, reconstruction and HER2-positive status correlated with CPM choice in
      this cohort. Occult malignancy was rare.

PMID- 24934587
TI  - Disseminated neoplasia in the soft-shell clam Mya arenaria: membrane lipid
      composition and functional parameters of circulating cells.
AB  - In a previous study we compared lipid composition and functional parameters of
      circulating cells from Cerastoderma edule affected or not by disseminated
      neoplasia (neoplastic cells vs hemocytes) (Le Grand et al. Chem Phys Lipids 167:9
      20 2013). Neoplastic cells presented morpho-functional modifications concomitant
      to striking membrane lipid alterations: the proportion of particular plasmalogen
      molecular species was drastically decreased. We wanted to test whether this
      pattern was representative of bivalve neoplastic cells. For the purpose, a
      similar study was conducted on another bivalve species affected by disseminated
      neoplasia, the soft-shell clam (Mya arenaria). Although total reactive oxygen
      species production was unaffected, M. arenaria neoplastic cells presented some
      functional alterations: phagocytosis activity was reduced by 33 %. However, lipid
      compositions were not drastically altered. Particularly, sterol and plasmalogen
      levels did not differ between both cell types (about 43 % of membrane lipids and
      35 % of phospholipids, respectively in hemocytes and neoplastic cells). This
      could be related to the fact that disseminated neoplasia was not related to
      hemolymph cell proliferation in M. arenaria (0.9 +/- 0.2 10(6)cell mL(-1),
      considering both healthy and neoplastic clams, n = 6). Nevertheless this study
      highlighted minor but specific alterations of membrane lipid composition in M.
      arenaria neoplastic cells. The only phospholipid subclass in which the fatty acid
      profile strongly differed between both cell types was serine plasmalogen
      (PlsSer), with neoplastic cells presenting lower specific enrichment of 20:1n-11
      in PlsSer. Such specific alteration of membrane lipid composition strengthened
      the assumption of an implication of key plasmalogen molecular species in this
      leukemia-like disease in bivalves. 

PMID- 24934588
TI  - Re-esterified palm oils, compared to native palm oil, do not alter fat
      absorption, postprandial lipemia or growth performance in broiler chicks.
AB  - Re-esterified palm oils are obtained from the chemical esterification of palm
      acid oils (rich in free fatty acids) with glycerol, both economically interesting
      by-products from oil refining and biodiesel industries, respectively. Thus, re
      esterified palm oils could be an economically interesting alternative to native
      palm oil in broiler chick diets. However, because they may have different
      physicochemical properties than have their corresponding native oil, we assessed
      the effect of fatty acid (FA) positional distribution within acylglycerol
      molecules and the effect of acylglycerol composition on FA apparent absorption,
      and their possible consequences on the evolution of postprandial lipemia and
      growth performance in broiler chicks. Seventy-two 1-day-old female broiler chicks
      were randomly distributed into 18 cages. The three treatments used were the
      result of a basal diet supplemented with 6 wt% of native palm oil (N-TAG), re
      esterified palm oil (E-TAG), or re-esterified palm oil high in mono- and
      diacylglycerols (E-MDAG). Chemical esterification raised the fraction of palmitic
      acid at the sn-2 position from 9.63 mol% in N-TAG oil to 17.9 mol% in E-TAG oil.
      Furthermore, E-MDAG oil presented a high proportion of mono- (23.1 wt%) and
      diacylglycerols (51.2 wt%), with FA mainly located at the sn-1,3 positions, which
      resulted in a lower gross-energy content and an increased solid-fat index at the
      chicken's body temperature. However, re-esterified palm oils did not alter fat
      absorption, postprandial lipemia, or growth performance, compared to native palm
      oil, so they can be used as alternative fat sources in broiler chick diets. 

PMID- 24934589
TI  - A novel assay of DGAT activity based on high temperature GC/MS of
      triacylglycerol.
AB  - Diacylglycerol acyltransferase (DGAT) catalyzes the final step in the acyl-CoA
      dependent biosynthesis of triacylglycerol (TAG), a high-energy compound composed
      of three fatty acids esterified to a glycerol backbone. In vitro DGAT assays,
      which are usually conducted with radiolabeled substrate using microsomal
      fractions, have been useful in identifying compounds and genetic modifications
      that affect DGAT activity. Here, we describe a high-temperature gas
      chromatography (GC)/mass spectrometry (MS)-based method for monitoring molecular
      species of TAG produced by the catalytic action of microsomal DGAT. This method
      circumvents the need for radiolabeled or modified substrates, and only requires a
      simple lipid extraction prior to GC. The utility of the method is demonstrated
      using a recombinant type-1 Brassica napus DGAT produced in a strain of
      Saccharomyces cerevisae that is deficient in TAG synthesis. The GC/MS-based assay
      of DGAT activity was strongly correlated with the typical in vitro assay of the
      enzyme using [1-(14)C] acyl-CoA as an acyl donor. In addition to determining DGAT
      activity, the method is also useful for determining substrate specificity and
      selectivity properties of the enzyme. 

PMID- 24934590
TI  - Maldi-tof fingerprinting of seminal plasma lipids in the study of human male
      infertility.
AB  - This study proposed lipid fingerprinting of human seminal plasma by mass
      spectrometry as an analytical method to differentiate biological conditions. For
      this purpose, we chose infertile men as a model to study specific conditions,
      namely: high and low seminal plasma lipid peroxidation levels (sub-study 1.1),
      high and low sperm nuclear DNA fragmentation (sub-study 1.2), and intervention
      status: before and after subinguinal microsurgical varicocelectomy (study 2).
      Study 1 included 133 patients, of which 113 were utilized for sub-study 1.1 and
      89 for sub-study 1.2. Study 2 included 17 adult men submitted to subinguinal
      varicocelectomy, before and 90 days after varicocelectomy. Lipids were extracted
      from seminal plasma and submitted to Matrix-Assisted Laser Desorption Ionization
      Quadrupole-Time-of-Flight Mass Spectrometry in the positive ionization mode.
      Spectra were processed using Waters((r)) MassLynx, and MetaboAnalyst online
      software was used for statistical analyses. For sub-studies 1.1 and 1.2, and
      study 2, univariate analysis revealed 8, 87 and 34 significant ions,
      respectively. Multivariate analysis was performed through PCA and PLS-DA. PCA
      generated 56, 32 and 34 components respectively for each study and these were
      submitted to logistic regression. A ROC curve was plotted and the area under the
      curve was equal to 97.4, 92.5 and 96.5%. PLS-DA generated a list of 19, 24 and 23
      VIP ions for sub-studies 1.1 and 1.2, and study 2, respectively. Therefore, this
      study established the lipid profile and comparison of patterns altered in
      response to specific biological conditions.

PMID- 24934592
TI  - Antifungal and antibacterial activity of Haliclona sp. from the Persian Gulf,
      Iran.
AB  - In this study, antifungal and antibacterial activities of diethyl ether, methanol
      and aqueous extracts of Haliclona sp. were assessed (in vitro). The antibacterial
      activity of the extracts was determined by broth dilution methods against
      clinical Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa and
      Gram-positive bacteria: Staphylococcus aureus aureus, Bacillus subtilis
      spizizenii. The antifungal activity of the extracts was determined by using a
      broth microdilution test against clinical fungi Candida albicans and Aspergillus
      fumigatus. Our results showed diethyl ether extract of Haliclona sp. was active
      on Gram-positive bacteria. In addition, methanol extract in comparison with
      diethyl ether extract had better activity against C. albicans (MIC: 0.75 mg/mL,
      MFC: 1.5mg/mL) and A. fumigatus (MIC: 2mg/mL, MFC: 3mg/mL). Aqueous extract had
      neither antifungal nor antibacterial activities. Based our results, Haliclona sp.
      can be considered as a source of novel antibiotic and antifungal.

PMID- 24934591
TI  - Enhanced solubility and oral bioavailability of gamma-tocotrienol using a self
      emulsifying drug delivery system (SEDDS).
AB  - The aim of this study was to evaluate the in vitro and in vivo performance of
      gamma-tocotrienol (gamma-T3) incorporated in a self-emulsifying drug delivery
      system (SEDDS) and to compare its enhanced performance to a commercially
      available product, namely Tocovid SuprabioTM (hereafter Tocovid), containing
      tocotrienols. The solubilization of gamma-T3 was tested in a dynamic in vitro
      lipolysis model followed by in vitro cellular uptake study for the lipolysis
      products. In addition, in vitro uptake studies using Caco2 cells were conducted
      at different concentrations of gamma-T3 prepared as SEDDS, Tocovid, or mixed
      micelles. gamma-T3 incorporated in SEDDS or Tocovid was orally administered to
      rats at different doses and absolute oral bioavailability from both formulations
      were determined. The dynamic in vitro lipolysis experiment showed about two fold
      increase in the solubilization of gamma-T3 prepared as SEDDS compared to Tocovid,
      which correlated with higher cellular uptake in the subsequent uptake studies. In
      vitro cellular uptake and in vivo oral bioavailability studies have shown a
      twofold increase in the cellular uptake and oral bioavailability of gamma-T3
      incorporated in SEDDS compared to Tocovid as a result of improvement in its
      solubility and passive uptake as confirmed by in vitro studies. In conclusion,
      incorporation of gamma-T3 in SEDDS formulation enhanced gamma-T3 solubilization
      and passive permeability, thus its cellular uptake and oral bioavailability when
      compared to Tocovid. 

PMID- 24934593
TI  - Postoperative mediastinitis due to Candida tropicalis: first reported case in
      Morocco.
AB  - Mediastinitis is a rare and serious nosocomial complication of cardiac surgery.
      It is estimated at less than 2% of cases of median sternotomy. We report the case
      of a postoperative mediastinitis due to Candida tropicalis. A 9-month-old baby
      was operated for complete repair of tetralogy of Fallot in which we isolated C.
      tropicalis from sternal purulent fluid and blood culture. The child did not
      survive, despite the initiation of antifungal therapy. The management of this
      type of infection requires an early diagnosis and an appropriate prolonged
      treatment, associated with effective preventive measures.

PMID- 24934594
TI  - [Definitive pacemaker implanted via the femoral route].

PMID- 24934596
TI  - Myasthenia Gravis: paradox versus paradigm in autoimmunity.
AB  - Myasthenia Gravis (MG) is a paradigm of organ-specific autoimmune disease (AID).
      It is mediated by antibodies that target the neuromuscular junction. The purpose
      of this review is to place MG in the general context of autoimmunity, to
      summarize the common mechanisms between MG and other AIDs, and to describe the
      specific mechanisms of MG. We have chosen the most common organ-specific AIDs to
      compare with MG: type 1 diabetes mellitus (T1DM), autoimmune thyroid diseases
      (AITD), multiple sclerosis (MS), some systemic AIDs (systemic lupus erythematous
      (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS)), as well as
      inflammatory diseases of the gut and liver (celiac disease (CeD), Crohn's disease
      (CD), and primary biliary cirrhosis (PBC)). Several features are similar between
      all AIDs, suggesting that common pathogenic mechanisms lead to their development.
      In this review, we address the predisposing factors (genetic, epigenetic,
      hormones, vitamin D, microbiota), the triggering components (infections, drugs)
      and their interactions with the immune system [1,2]. The dysregulation of the
      immune system is detailed and includes the role of B cells, Treg cells, Th17 and
      cytokines. We particularly focused on the role of TNF-alpha and interferon type I
      whose role in MG is very analogous to that in several other AIDS. The implication
      of AIRE, a key factor in central tolerance is also discussed. Finally, if MG is a
      prototype of AIDS, it has a clear specificity compared to the other AIDS, by the
      fact that the target organ, the muscle, is not the site of immune infiltration
      and B cell expansion, but exclusively that of antibody-mediated pathogenic
      mechanisms. By contrast, the thymus in the early onset subtype frequently
      undergoes tissue remodeling, resulting in the development of ectopic germinal
      centers surrounded by high endothelial venules (HEV), as observed in the target
      organs of many other AIDs. 

PMID- 24934595
TI  - Characterization of an injectable, degradable polymer for mechanical
      stabilization of mandibular fractures.
AB  - This study investigated the use of injectable poly(propylene fumarate) (PPF)
      formulations for mandibular fracture stabilization applications. A full factorial
      design with main effects analysis was employed to evaluate the effects of the
      PPF:N-vinyl pyrrolidone (NVP, crosslinking agent) ratio and dimethyl toluidine
      (DMT, accelerator) concentration on key physicochemical properties including
      setting time, maximum temperature, mechanical properties, sol fraction, and
      swelling ratio. Additionally, the effects of formulation crosslinking time on the
      mechanical and swelling properties were investigated. The results showed that
      increasing the PPF:NVP ratio from 3:1 to 4:1 or decreasing the DMT concentration
      from 0.05 to 0.01 v/w % significantly decreased all mechanical properties as well
      as significantly increased the sol fraction and swelling ratio. Also, increasing
      the crosslinking time at 37 degrees C from 1 to 7 days significantly increased
      all mechanical properties and decreased both the sol fraction and swelling ratio.
      This study further showed that the flexural stiffness of ex vivo stabilized
      rabbit mandibles increased from 1.7 +/- 0.3 N/mm with a traditional mini-plate
      fixator to 14.5 +/- 4.1 N/mm for the 4:1 (0.05 v/w % DMT) PPF formulation at day
      1. Overall, the formulations tested in this study were found to have properties
      suitable for potential further consideration in mandibular fracture fixation
      applications.

PMID- 24934597
TI  - Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69
      expression.
AB  - Although FoxP3(+) regulatory T cells are key players in the maintenance of immune
      tolerance and autoimmunity, the lack of specific markers constitute an obstacle
      to their use for immunotherapy protocols. In this study, we have investigated the
      role of the C-type lectin receptor CD69 in the suppressor function of Tregs and
      maintenance of immune tolerance towards harmless inhaled antigens. We identified
      a novel FoxP3(+)CD69(+) Treg subset capable to maintain immune tolerance and
      protect to developing inflammation. Although CD69(+) and CD69(-)FoxP3(+) Tregs
      exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4,
      ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of
      TGFbeta and have potent suppressor activity. This activity is regulated by STAT5
      and ERK signaling pathways and is impaired by antibody-mediated down-regulation
      of CD69 expression. Moreover, immunotherapy with FoxP3(+)CD69(+) Tregs restores
      the homeostasis in Cd69(-/-) mice, that fail to induce tolerance, and is also
      highly proficient in the prevention of inflammation. The identification of the
      FoxP3(+)CD69(+) Treg subset paves the way toward the development of new
      therapeutic strategies to control immune homeostasis and autoimmunity.

PMID- 24934599
TI  - Immunomodulation neuroprotection and remyelination - the fundamental therapeutic
      effects of glatiramer acetate: a critical review.
AB  - Multiple sclerosis (MS) is a multifaceted heterogeneous disease with various
      patterns of tissue damage. In addition to inflammation and demyelination,
      widespread axonal and neuronal pathologies are central components of this
      disease. MS therapies aim to restrain the pathological processes, enhance
      protective mechanisms, and prevent disease progression. The amino acid copolymer,
      glatiramer acetate (GA, Copaxone), an approved treatment for MS, has a unique
      mode of action. Evidence from the animal model experimental autoimmune
      encephalomyelitis (EAE) and from MS patients indicates that GA affects various
      levels of the innate and the adaptive immune response, inducing deviation from
      the pro-inflammatory to the anti-inflammatory pathways. This includes competition
      for the binding of antigen presenting cells, driving dendritic cells, monocytes,
      and B-cells towards anti-inflammatory responses, induction of Th2/3 and T
      regulatory cells, and downregulating of both Th1 and Th-17 cells. The immune
      cells induced by GA reach the inflamed disease organ and secrete in situ anti
      inflammatory cytokines alleviating the pathological processes. Furthermore,
      cumulative findings have revealed that in addition to its immunomodulatory
      activities GA promotes neuroprotective repair processes such as neurotrophic
      factors secretion and remyelination. This review aims to provide a comprehensive
      overview on the diverse mechanism of action of GA in EAE/MS, in particular on the
      in situ effect of GA and its ability to generate neuroprotection and repair in
      the CNS. In view of its immunomodulatory activity, the beneficial effects of GA
      in various models of additional autoimmune related pathologies, such as immune
      rejection and inflammatory bowel disease (IBD), are also presented. 

PMID- 24934598
TI  - MBD2 regulates TH17 differentiation and experimental autoimmune encephalomyelitis
      by controlling the homeostasis of T-bet/Hlx axis.
AB  - Unlike genetic alterations, epigenetic modifications are reversible and amenable
      to pharmacological interventions, which make them appealing targets for clinical
      therapy. However, little is known about epigenetic regulation in experimental
      autoimmune encephalomyelitis (EAE). Here we demonstrated that methyl-CpG-binding
      domain protein 2 (MBD2), an epigenetic regulator, controls autoimmunity and EAE
      through T-bet/Hlx. Tbx21 and Hlx underwent a DNA methylation turnover upon
      polarizations and a unique methylation pattern was essential for TH17
      development. Loss of Mbd2 resulted in a defect for reading the information
      encoded by this methylation turnover, which disrupted the homeostasis of T
      bet/Hlx axis and suppressed TH17 differentiation. DNA demethylation induced
      similar effect on helper T cell differentiation. Therefore, Mbd2(-/-) mice were
      completely protected from EAE. Pathogenic splenocytes isolated from wild-type
      mice challenged with MOG35-55 could adoptively transfer disease to Mbd2(-/-)
      mice. In addition, Mbd2(-/-) mice reconstituted with unstimulated wild-type
      splenocytes developed EAE as wild-type mice did. These data would provide novel
      insights into epigenetic regulation of EAE. 

PMID- 24934600
TI  - Modulating inflammatory cell responses to spinal cord injury: all in good time.
AB  - Spinal cord injury can have a range of debilitating effects, permanently
      impacting a patient's quality of life. Initially thought to be an immune
      privileged site, the spinal cord is able to mount a timely and well organized
      inflammatory response to injury. Intricate immune cell interactions are
      triggered, typically consisting of a staggered multiphasic immune cell response,
      which can become deregulated if left unchecked. Although several immunomodulatory
      compounds have yielded success in experimental rodent spinal cord injury models,
      their translation to human clinical studies needs further consideration. Because
      temporal differences between rodent and human inflammatory responses to spinal
      cord injury do exist, drug delivery timing will be a crucial component in
      recovery from spinal cord injury. Given too early, immunomodulatory therapies may
      impede beneficial inflammatory reactions to the injured spinal cord or even miss
      the opportunity to dampen delayed harmful autoimmune processes. Therefore, this
      review aims to summarize the temporal inflammatory response to spinal cord
      injury, as well as detailing specific immune cell functions. By clearly defining
      the chronological order of inflammatory events after trauma, immunomodulatory
      drug delivery timing can be better optimized. Further, we compare spinal cord
      injury-induced inflammatory responses in rodent and human studies, enabling
      clinicians to consider these differences when initiating clinical trials.
      Improved understanding of the cellular immune response after spinal cord injury
      would enhance the efficacy of immunomodulatory agents, enabling combined
      therapies to be considered.

PMID- 24934601
TI  - Direct electrochemical and AFM detection of amyloid-beta peptide aggregation on
      basal plane HOPG.
AB  - Amyloidogenesis is associated with more than 30 human diseases, including
      Alzheimer's which is related to aggregation of beta-amyloid peptide (Abeta).
      Here, consecutive stages of Abeta42 aggregation and amyloid fibril formation were
      followed electrochemically via oxidation of tyrosines in Abeta42 adsorbed on the
      basal plane graphite electrode and directly correlated with Abeta42 morphological
      changes observed by atomic force microscopy of the same substrate. The results
      offer new tools for analysis of mechanisms of Abeta aggregation. 

PMID- 24934602
TI  - Thoracodorsal nerve transfer for elbow flexion reconstruction in infraclavicular
      brachial plexus injuries.
AB  - PURPOSE: To report the clinical results of thoracodorsal nerve (TDN) transfer to
      the biceps nerve for elbow flexion restoration in infraclavicular brachial plexus
      injuries. METHODS: Five male patients, mean age 33 years and affected with
      infraclavicular brachial plexus injuries, underwent a direct coaptation of the
      TDN to the nerve to the biceps an average of 8 months after injury. The procedure
      included the transfer of a branch of the TDN to the musculocutaneous nerve in 2
      patients. RESULTS: All patients achieved M4 elbow flexion strength according to
      the British Medical Research Council scale at a mean follow-up of 22 months.
      CONCLUSIONS: Direct TDN transfer seems to be a useful surgical procedure for
      restoring elbow flexion in patients with infraclavicular brachial plexus
      injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24934603
TI  - Discrepancies between meeting abstracts and subsequent full text publications in
      hand surgery.
AB  - PURPOSE: Research abstracts presented during the proceedings of an annual meeting
      are often cited and can influence clinical practice. Prior studies show that
      roughly 50% of abstracts at American Society for Surgery of the Hand meetings are
      eventually published. Yet, it is unknown how often the results or conclusions of
      published studies differ from the podium presentation. The objective of this
      study was to quantify the differences between abstracts presented during the
      annual meeting of the American Society for Surgery of the Hand and the resulting
      manuscripts. METHODS: We retrospectively reviewed every abstract delivered as a
      podium presentation at the American Society for Surgery of the Hand annual
      meeting from 2000 to 2010. We searched the PubMed database for matching
      publications and compared authorship, country of origin, hypothesis, study design
      and methodology, changes in study groups or populations, results, and
      conclusions. RESULTS: Of 798 total abstracts, we analyzed 719 involving the hand,
      wrist, and brachial plexus. Fifty-six different journals published 393 of the
      abstracts, for a 49% publication rate. Mean time to publication was 18 months
      with a median of 14 and maximum of 122 months. There were inconsistencies between
      the results and/or conclusions in 14% of full-length articles compared with the
      abstract presented at the meeting. A total of 9% of articles were published with
      fewer subjects. Authorships changes were noted in 54% of publications.
      CONCLUSIONS: Abstracts represent preliminary investigations and major and minor
      changes occur before subsequent publication. Caution should be exercised in
      referencing abstracts or altering clinical practice based on their content. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Economic/decision analysis IV.

PMID- 24934604
TI  - Automated Patch Clamp Analysis of nAChalpha7 and Na(V)1.7 Channels.
AB  - Automated patch clamp devices are now commonly used for studying ion channels. A
      useful modification of this approach is the replacement of the glass pipet with a
      thin planar glass layer with a small hole in the middle. Planar patch clamp
      devices, such as the three described in this unit, are overtaking glass pipets in
      popularity because they increase throughput, are easier to use, provide for the
      acquisition of high-quality and information-rich data, and allow for rapid
      perfusion and temperature control. Covered in this unit are two challenging
      targets in drug discovery: voltage-gated sodium subtype 1.7 (Na(V)1.7) and
      nicotinic acetylcholine alpha7 receptors (nAChalpha7R). Provided herein are
      protocols for recording activation and inactivation kinetics of Na(V)1.7, and
      activation and allosteric modulation of nAChalpha7R.

PMID- 24934605
TI  - Electrophysiological Studies of Voltage-Gated Sodium Channels Using QPatch HT, an
      Automated Patch-Clamp System.
AB  - Voltage-gated sodium (Na(v)) channels are highly sensitive to membrane potential
      and have fast gating kinetics. Patch clamp electrophysiology has long been the
      gold standard for studying these channels. Combining high throughput with high
      information content/accuracy, automated patch clamp technologies have emerged as
      critical tools in ion channel drug discovery. Described in this unit is the use
      of QPatch, one of the automated patch clamp systems, to study Na(v) channel
      function and pharmacology.

PMID- 24934606
TI  - Overview of genetically engineered mouse models of colorectal carcinoma to enable
      translational biology and drug development.
AB  - Preclinical models for colorectal cancer (CRC) are critical for translational
      biology and drug development studies to characterize and treat this condition.
      Mouse models of human cancer are particularly popular because of their relatively
      low cost, short life span, and ease of use. Genetically engineered mouse models
      (GEMMs) of CRC are engineered from germline or somatic modification of critical
      tumor suppressor genes and/or oncogenes that drive mutations in human disease.
      Detailed in this overview are the salient features of several useful colorectal
      cancer GEMMs and their value as tools for translational biology and preclinical
      drug development.

PMID- 24934608
TI  - Times change: the NVMO journal going from Dutch to English and from paper to
      electronics.

PMID- 24934612
TI  - Rhodanine dye-based small molecule acceptors for organic photovoltaic cells.
AB  - The solution-processable small molecules based on carbazole or fluorene
      containing rhodanine dyes at both ends were synthesized and introduced as
      acceptors in organic photovoltaic cells. The high energy levels of their lowest
      unoccupied molecular orbitals resulted in a power conversion efficiency of 3.08%
      and an open circuit voltage of up to 1.03 V. 

PMID- 24934611
TI  - How many radiographs are needed to detect angular stable head screw cut outs of
      the proximal humerus - a cadaver study.
AB  - INTRODUCTION: Cut out of locking head screws is the most common complication of
      locking plates in fracture fixation of the proximal humerus with potentially
      disastrous consequences. Aim of the study was to find the single best and
      combination of radiographic projections to reliably detect screw cut outs.
      MATERIALS AND METHODS: The locking plate was fixed to six cadaveric proximal
      humeri. Six different radiographs were performed: anteriorposterior in internal
      (apIR), in neutral (ap0) and in 30 degrees  external rotation (apER); axial in 30
      degrees  (ax30) and 60 degrees  (ax60) abduction and an outlet view. Each head
      screw (n=9) was sequentially exchanged to perforate the humeral head with the tip
      and all radiographs were repeated for each cut out. Randomized image reading by
      two blinded examiners for cut out was done for single projection and
      combinations. RESULTS: Interrater agreement was 0.72-0.93. Best single projection
      was ax30 (sensitivity 76%) and the worst was the outlet view (sens. 17%).
      Standard combination of apIR/outlet reached a sens. of 54%. The best combination
      of two was: apER/ax30 (90% sens.), of three: apIR/apER/ax30 (96% sens.) and of
      four: apIR/ap0/apER/ax30 (100% sens.). CONCLUSION: Standard radiographs
      (ap/outlet), especially in internal rotation, may miss nearly half of screw cut
      outs. Single best radiographic projection was an axial view with 30 degrees 
      abduction. To account for all cut outs and correct screw position a combination
      of four projections was needed. These simple and feasible intraoperative and
      postoperative radiographs help to detect screw perforations of the locking plate
      reliably. LEVEL OF EVIDENCE: I (Study of Diagnostic Test).

PMID- 24934609
TI  - Assessment of mitral regurgitation severity by Doppler color flow mapping of the
      vena contracta in dogs.
AB  - BACKGROUND: Quantitative and semiquantitative methods have been proposed for the
      assessment of MR severity, and though all are associated with limitations.
      Measurement of vena contracta width (VCW) has been used in clinical practice.
      OBJECTIVE: To measure the VCW in dogs with different levels of MR severity.
      ANIMALS: Two hundred and seventy-nine dogs were classified according to 5 levels
      of MR severity. METHODS: This was a retrospective study. EROA and regurgitant
      volume calculated by the PISA method, were measured and indexed to BSA.
      Descriptive statistics were calculated for VCW and VCW index for all categories
      of MR severity. Spearman's rank correlation coefficients (rhos ) were calculated
      to compare the results of the different methods (VCW and VCW index vs RV PISA, RV
      PISA index, EROA, EROA index), and between VCW and VCW index versus MR severity.
      RESULTS: All Spearman's rank correlation coefficients were significant (P <
      .001). The median values of VCW resulted of 2.9 mm (IQR 3.4-2.5) and of 4.6 mm
      (IQR 5.4-4.1) in the groups previously classified as mild-to-moderate and
      moderate-to-severe, respectively. The median values of VCW index resulted of 4.4
      mm/m(2) (IQR = 5.5-4.2) in mild-to-moderate MR and of 10.8 mm/m(2) (IQR = 12.8
      9.4) in moderate-to-severe MR. CONCLUSION AND CLINICAL IMPORTANCE: This is not a
      validation study against any previously validated invasive gold standard, the VCW
      method has proved easy to employ and it might be an additional tool in
      quantifying disease severity that supports, rather than replace, data coming from
      other techniques in daily clinical practice and research.

PMID- 24934610
TI  - Persistence and discontinuation of adjuvant endocrine therapy in women with
      breast cancer.
AB  - AIMS: Although 8-73 % of breast cancer patients who receive adjuvant endocrine
      therapy discontinue it, discontinuation is little studied in Asian breast cancer
      patients. MATERIALS AND METHODS: To determine frequency and reasons for
      discontinuation at a single institution, we reviewed records and database
      information for women with hormone receptor-positive breast cancer who were
      treated at the National Kyushu Cancer Center 2001-2006, defining "persistence" as
      continued endocrine treatment (even when physicians decided to stop because of
      recurrent disease or severe adverse effects), and "discontinuation" as ending
      therapy due to patient's wishes. RESULTS: Among 686 patients who started adjuvant
      endocrine therapy, 607 patients (88 %) persisted, 79 patients (12 %)
      discontinued. Of the 79 patients who discontinued, 37 (46 %) did so because of
      side effects, 26 (33 %) stopped appointments, 11 (14 %) stopped for "no
      particular reason", 4 (5 %) to get pregnant, and 1 (1 %) for economic reasons.
      The rate of persistence was higher in patients with lymph node involvement than
      in those without lymph node involvement (92 vs. 87 %; P = 0.03). CONCLUSIONS:
      Clinicians should discuss side effects with patients, both as part of informed
      consent and to prepare them to continue therapy, and should be aware that over
      time, patients' reasons for discontinuation change.

PMID- 24934613
TI  - Hepatoprotective effect of silymarin on di(2-ethylhexyl)phthalate (DEHP) induced
      injury in liver FL83B cells.
AB  - Di(2-ethylhexyl)phthalate (DEHP), is a toxic environmental pollutant in our life
      which can contaminate air, water, and soil. The hepatoprotective effect of
      silymarin on DEHP-induced injury in FL83B mouse liver cells was investigated by
      analyzing the cell viability, lactate dehydrogenase (LDH), alanine
      aminotransferase (ALT), cell cycle arrest, and cell morphology. The results
      revealed that cell viability decreased while released LDH and ALT increased with
      the increase of DEHP concentrations. Moreover, cell population of sub-G1 and S
      phase increased as the concentrations of DEHP increased. Silymarin at 25 MUM
      achieved the highest hepatoprotective effect and exhibited 79% cell viability
      while only 46% cell viability was found in DEHP injured control. It was also
      found to reduce LDH release and cell populations of sub-G1 and S phase.
      Therefore, silymarin could ameliorate DEHP-induced injury and have potential to
      be further developed as a natural ingredient of health food against phthalate
      plasticizers induced liver injury.

PMID- 24934618
TI  - Laboratory to community: chemoprevention is the answer.
AB  - In the current issue, Johnson and colleagues present exciting results, using
      biomarkers involved in aflatoxin B1 (AFB1)-induced hepatocarcinogenesis, as an
      example of a conceptual framework to target mechanisms of action in developing
      chemopreventive agents. Their innovative approach offers considerable promise for
      a field that has long been neglected. Proof-of-principle was demonstrated using a
      synthetic triterpenoid (CDDO-Im), which activates Nrf2 signal transduction
      pathway, inhibits formation of AFB1-induced DNA adducts and neoplastic hepatic
      foci, and alters the expression of genes associated with aflatoxin-mediated
      toxicity.

PMID- 24934617
TI  - Childhood maltreatment, adult attachment and psychotic symptomatology: a study in
      patients, siblings and controls.
AB  - PURPOSE: The association between childhood maltreatment (ChM) and psychotic
      disorders is well established. However, there is an ongoing debate about which
      factors account for this relationship. One explanation is that the relationship
      between ChM and psychosis is mediated by adult attachment style. Therefore, in
      this study, we aimed to investigate whether adult attachment style mediates the
      relationship between ChM and positive and negative symptomatology. METHODS: We
      investigated the relation between ChM and psychotic symptoms, taking into account
      levels of (insecure) attachment, in 131 patients with psychotic illness, 123
      siblings and 72 controls. ChM was assessed with the Childhood Trauma
      Questionnaire (CTQ). Attachment dimensions of anxiety and avoidance were measured
      using the Psychosis Attachment Measure (PAM). RESULTS: In both patients and
      siblings, ChM predicted positive symptoms and this relationship was partly
      mediated by attachment style. This relationship was found to be stronger for
      siblings than for patients. ChM predicted negative symptoms in patients and
      siblings. In the patient sample, attachment style did not mediate the
      relationship between ChM and negative symptoms, whereas attachment style was
      found to be a mediator in the sibling sample. CONCLUSIONS: ChM was associated
      with positive and negative symptomatology in both patients and siblings.
      Particularly in siblings, the relationship between ChM and psychosis seems to be
      mediated by adult attachment style. Perhaps attachment style may play a more
      prominent role on a subclinical level.

PMID- 24934620
TI  - How to undermine general practice.

PMID- 24934619
TI  - Of mice, rats, and men: could Nrf2 activation protect against aflatoxin
      heptocarcinogenesis in humans?
AB  - In this issue, Johnson and colleagues provide a remarkable demonstration of the
      potential for "chemoprevention" of cancer from mutagenic chemicals. The authors
      demonstrated complete protection of rats from a carcinogenic treatment regimen
      with the potent dietary mutagen and hepatocarcinogen, aflatoxin B1 (AFB) by
      pretreatment with a synthetic oleanane triterpenoid, 1-[2-cyano-3-,12-dioxooleana
      1,9(11)-dien-28-oyl]imidazole (CDDO-Im). This study is notable for two reasons:
      (i) Activation of the Nrf2/Keap1/ARE "antioxidant response" pathway by CDDO-Im
      conferred complete protection against AFB-induced hepatocellular carcinomas in
      the Fisher F344 rat (a strain frequently used in life-time carcinogenicity
      bioassays), and (ii) extensive AFB-DNA adduct formation was seen in all animals
      at early time points, including those treated with CDDO-Im, albeit at lower
      levels (~30% of the untreated animals), suggesting a strong divergence in the
      association between early DNA-damaging events, and tumor formation later in life.
      The authors suggest that this provides compelling experimental support for the
      concept of carcinogenic "thresholds" for mutagenic chemicals, because the
      treatment reduced persistent, mutagenic adducts (AFB-FAPyr adducts) only by 70%,
      but nearly completely eliminated tumors after approximately 2 years and
      preneoplastic lesions 6 weeks after the last dose of AFB.

PMID- 24934621
TI  - Sulfate assimilation pathway intermediate  phosphoadenosine 59-phosphosulfate
      acts as a  signal molecule affecting production of curli fibres  in Escherichia
      coli.
AB  - The enterobacterium Escherichia coli can utilize a variety of molecules as sulfur
      sources, including cysteine, sulfate, thiosulfate and organosulfonates. An
      intermediate of the sulfate assimilation pathway, adenosine 59-phosphosulfate
      (APS), also acts as a signal molecule regulating the utilization of different
      sulfur sources. In this work, we show that inactivation of the cysH gene, leading
      to accumulation of phosphoadenosine 59-phosphosulfate (PAPS), also an
      intermediate of the sulfate assimilation pathway, results in increased surface
      adhesion and cell aggregation by activating the expression of the curli-encoding
      csgBAC operon. In contrast, curli production was unaffected by the inactivation
      of any other gene belonging to the sulfate assimilation pathway. Overexpression
      of the cysH gene downregulated csgBAC transcription, further suggesting a link
      between intracellular PAPS levels and curli gene expression. In addition to curli
      components, the Flu, OmpX and Slp proteins were also found in increased amounts
      in the outer membrane compartment of the cysH mutant; deletion of the
      corresponding genes suggested that these proteins also contribute to surface
      adhesion and cell surface properties in this strain. Our results indicate that,
      similar to APS, PAPS also acts as a signal molecule, albeit with a distinct
      mechanism and role: whilst APS regulates organosulfonate utilization, PAPS would
      couple availability of sulfur sources to remodulation of the cell surface, as
      part of a more global effect on cell physiology.

PMID- 24934607
TI  - Surgery and neurodevelopmental outcome of very low-birth-weight infants.
AB  - IMPORTANCE: Reduced death and neurodevelopmental impairment among infants is a
      goal of perinatal medicine. OBJECTIVE: To assess the association between surgery
      during the initial hospitalization and death or neurodevelopmental impairment of
      very low-birth-weight infants. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      cohort analysis was conducted of patients enrolled in the National Institute of
      Child Health and Human Development Neonatal Research Network Generic Database
      from 1998 through 2009 and evaluated at 18 to 22 months' corrected age. Twenty
      two academic neonatal intensive care units participated. Inclusion criteria were
      birth weight 401 to 1500 g, survival to 12 hours, and availability for follow-up.
      A total of 12 111 infants were included in analyses. EXPOSURES: Surgical
      procedures; surgery also was classified by expected anesthesia type as major
      (general anesthesia) or minor (nongeneral anesthesia). MAIN OUTCOMES AND
      MEASURES: Multivariable logistic regression analyses planned a priori were
      performed for the primary outcome of death or neurodevelopmental impairment and
      for the secondary outcome of neurodevelopmental impairment among survivors.
      Multivariable linear regression analyses were performed as planned for the
      adjusted mean scores of the Mental Developmental Index and Psychomotor
      Developmental Index of the Bayley Scales of Infant Development, Second Edition,
      for patients born before 2006. RESULTS: A total of 2186 infants underwent major
      surgery, 784 had minor surgery, and 9141 infants did not undergo surgery. The
      risk-adjusted odds ratio of death or neurodevelopmental impairment for all
      surgery patients compared with those who had no surgery was 1.29 (95% CI, 1.08
      1.55). For patients who had major surgery compared with those who had no surgery,
      the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52
      (95% CI, 1.24-1.87). Patients classified as having minor surgery had no increased
      adjusted risk. Among survivors who had major surgery compared with those who had
      no surgery, the adjusted risk of neurodevelopmental impairment was greater and
      the adjusted mean Bayley scores were lower. CONCLUSIONS AND RELEVANCE: Major
      surgery in very low-birth-weight infants is independently associated with a
      greater than 50% increased risk of death or neurodevelopmental impairment and of
      neurodevelopmental impairment at 18 to 22 months' corrected age. The role of
      general anesthesia is implicated but remains unproven.

PMID- 24934622
TI  - Arabidopsis ZDP DNA 3'-phosphatase and ARP endonuclease function in 8-oxoG repair
      initiated by FPG and OGG1 DNA glycosylases.
AB  - Oxidation of guanine in DNA generates 7,8-dihydro-8-oxoguanine (8-oxoG), an
      ubiquitous lesion with mutagenic properties. 8-oxoG is primarily removed by DNA
      glycosylases distributed in two families, typified by bacterial Fpg proteins and
      eukaryotic Ogg1 proteins. Interestingly, plants possess both Fpg and Ogg1
      homologs but their relative contributions to 8-oxoG repair remain uncertain. In
      this work we used Arabidopsis cell-free extracts to monitor 8-oxoG repair in wild
      type and mutant plants. We found that both FPG and OGG1 catalyze excision of 8
      oxoG in Arabidopsis cell extracts by a DNA glycosylase/lyase mechanism, and
      generate repair intermediates with blocked 3'-termini. An increase in oxidative
      damage is detected in both nuclear and mitochondrial DNA from double fpg ogg1
      mutants, but not in single mutants, which suggests that a single deficiency in
      one of these DNA glycosylases may be compensated by the other. We also found that
      the DNA 3'-phosphatase ZDP (zinc finger DNA 3'-phosphoesterase) and the
      AP(apurinic/apyirmidinic) endonuclease ARP(apurinic endonuclease redox protein)
      are required in the 8-oxoG repair pathway to process the 3'-blocking ends
      generated by FPG and OGG1. Furthermore, deficiencies in ZDP and/or ARP decrease
      germination ability after seed deteriorating conditions. Altogether, our results
      suggest that Arabidopsis cells use both FPG and OGG1 to repair 8-oxoG in a
      pathway that requires ZDP and ARP in downstream steps. 

PMID- 24934623
TI  - Variation in inpatient costs of hematopoietic cell transplantation among
      transplant centers in the United States.

PMID- 24934624
TI  - Nomadic beekeeper movements create the potential for widespread disease in the
      honeybee industry.
AB  - OBJECTIVE: To examine the nomadic movements of Australian beekeepers and
      determine their potential to assist the spread of pests and diseases. METHODS: A
      questionnaire was mailed to all beekeepers in Australia who maintained >100
      hives, requesting information on the location of their home base, locations used
      throughout the year and the crops that the bees fed on in each location. The
      information was analysed using network analysis software and a geographic
      information system. RESULTS: Nomadic Australian beekeepers formed a connected
      network linking 288 locations from central Queensland to western Victoria. A
      second, smaller network included 42 locations in south-eastern South Australia.
      Almond orchards in Robinvale and Boundary Bend and lucerne seed production in
      Keith were locations of major hive congregations driven by the opportunity to
      provide paid pollination services. In the 3 months after completion of almond
      pollination in August 2008, movement of hives occurred from Robinvale and
      Boundary Bend to 49 locations, ranging from south-east Queensland to south-west
      Victoria. DISCUSSION: The movements identified in this study highlight the
      potential for rapid spread of disease or pests throughout the beekeeping industry
      should an incursion occur.

PMID- 24934625
TI  - Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case
      control study.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life
      threatening complication of fertility treatment. This study evaluated pregnancy
      outcomes of women hospitalized for severe OHSS. A case-control study was
      performed of 125 women who were hospitalized due to severe OHSS compared with a
      control group, consisting of 156 women matched by age and aetiology of
      infertility, who conceived via IVF and did not develop OHSS. Among women with
      singleton pregnancies, patients with severe OHSS delivered significantly earlier
      (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared
      with the matched controls. Similarly, rates of preterm delivery (<34 weeks of
      gestation: 8.9% versus 0%, P < 0.01; <37 weeks of gestation: 20.5% versus 5.1%, P
      < 0.01) were significantly increased among patients in the study group. There
      were no between-group differences in the rates of gestational diabetes,
      gestational hypertension and intrauterine growth restriction. In contrast, twin
      pregnancies following OHSS were not significantly different from matched control
      twins, with regard to the rates of delivery <34 weeks and <37 weeks of gestation,
      gestational diabetes, gestational hypertension and intrauterine growth
      restriction. In conclusion, severe OHSS at early gestation is associated with
      adverse pregnancy outcome only in singleton gestations.

PMID- 24934626
TI  - On the cost and prevention of iatrogenic multiple pregnancies.
AB  - Multiple pregnancies are an undesirable complication of IVF and of ovulation
      induction and/or ovulation enhancement without IVF. Studies based on published
      population data and data from the Centers for Disease Control and Prevention
      indicate that savings from the mitigation of iatrogenic multiples would save
      money in the billions (10(9)) of US dollars on a national basis. The aim of this
      study was to determine whether, using real data from a major regional insurance
      carrier for the interval 2005-2009 covering obstetric costs requiring
      hospitalization and neonatal costs through the first year, it was possible to
      show that the cost saved by eliminating iatrogenic multiple births would be
      adequate to fund a protocol to minimize iatrogenic multiple births. The net
      savings on an annual basis for the study group of 13,478 was about US$4.4
      million. Applying the regional findings to national data suggests savings of
      approximately US$6.3 billion if national iatrogenic multiples were eliminated.
      These findings indicate that the health insurance industry should be able to
      offer infertility coverage at a lower rate by requiring a treatment algorithm
      designed to essentially eliminate iatrogenic multiple pregnancies. It is
      concluded that efforts should be made to assure a singleton birth when treating
      infertility. 

PMID- 24934627
TI  - Treatment of severe tetanus with intrathecal baclofen via implantable infusion
      device: a case report.
AB  - OBJECTIVE: Severe tetanus remains a serious issue in less developed countries,
      leading to prolonged hospitalization due to prolonged neuromuscular contraction
      of muscles. We present a case of severe tetanus in the United States that was
      successfully managed with intrathecal baclofen. CASE REPORT: A 42-year-old male
      without tetanus vaccination history presented to the emergency department with
      intractable jaw pain and worsening diffuse muscle contractures due to severe
      generalized tetanus requiring prolonged paralysis and ventilator support. After
      14 days of continuous neuromuscular treatment with benzodiazepines, vecuronium,
      propofol, and magnesium sulfate, a baclofen pump trial was performed 14 days post
      admission as an alternative to prolonged neuromuscular blockade. After
      demonstrable improvement in spasms and paroxysmal contractures due to intrathecal
      baclofen (ITB), a baclofen pump was implanted on hospital day 17. The catheter
      was threaded to T4 for maximal effect of intrathecal baclofen on the upper and
      lower extremities at an initial rate of 100 MUg/day. ITB was titrated upward, the
      vecuronium was slowly weaned, and the patient was weaned off a ventilator by day
      14 of ITB treatment. At an ITB dose of 450 MUg/day, propofol was discontinued.
      ITB was continued over the next four weeks and eventually weaned over the next
      two weeks. The ITB pump was removed eight weeks after placement, and the patient
      was successfully discharged to home. CONCLUSION: Due to prolonged muscle weakness
      associated with long-term use of paralytic agents and sedation, early ITB trial
      and pump placement should be considered as an alternative in the treatment of
      severe tetanus to shorten length of stay and improve the functional outcome of
      the patient.

PMID- 24934628
TI  - Phase transitions in rare earth tellurides under pressure.
AB  - Using first-principles calculations we have studied the valence and structural
      transitions of the rare earth monotellurides RTe (R = Ce, Pr, Nd, Pm, Sm, Eu, Gd,
      Tb, Dy, Ho, Er, Tm and Yb) under pressure. The self-interaction corrected local
      spin-density approximation is used to establish the ground state valence
      configuration as a function of volume for the RTe in both the NaCl (B1) and CsCl
      (B2) structures. We find that in ambient conditions all the RTe are stabilized in
      the B1 structure. A trivalent (R(3+)) rare earth ground state is predicted for
      the majority of the RTe, with the exception of SmTe, EuTe, DyTe, TmTe and YbTe,
      where the fully localized divalent (R(2+)) rare earth configuration is found to
      be energetically most favourable. Under pressure, the trivalent RTe undergo
      structural transitions to the B2 structure without associated valence transition.
      The divalent RTe on the other hand are characterized by a competition between the
      structural and electronic degrees of freedom, and it is the degree of f-electron
      delocalization that determines the sequence of phase transitions. In EuTe and
      YbTe, where respectively the half-filled and filled shells result in a very
      stable divalent configuration, we find that it is the structural B1 -> B2
      transition that occurs first, followed by the R(2+) -> R(3+) valence transition
      at even higher pressures. In SmTe, DyTe and TmTe, the electronic transition
      occurs prior to the structural transition. With the exception of YbTe, the
      calculated transition pressures are found to be in good agreement with
      experiment. 

PMID- 24934629
TI  - Variables affecting postoperative tissue perfusion monitoring in free flap breast
      reconstruction.
AB  - Postoperative flap monitoring is a key component for successful free tissue
      transfer. Tissue oxygen saturation measurement (TOx) with near-infrared
      spectrophotometry (NIRS) is a method used for this purpose. The aim of this study
      was to identify external variables that can affect TOx. Patients who had breast
      reconstruction with free flaps were monitored prospectively and intra-operative
      details were recorded. Flap TOx was recorded with NIRS pre-extubation,
      postextubation, and then every four hours for 36 hours. At each of these time
      points, blood oxygen saturation (SO2), amount of supplemental oxygen, and blood
      pressure were recorded. Thirty flaps were monitored. Initially, a significant
      trend over time was detected such that for every increase of 24 hours, TOx
      decreased on average by 2.1% (P = 0.025). However, when accounting for SO2
      levels, this decrease was no longer significant (P = 0.19). An increase by 1% in
      SO2 produced an increase in TOx reading of 0.36 (P = 0.007). The amount of
      supplemental O2, systolic blood pressure, and diastolic blood pressure did not
      have a significant impact on TOx (P > 0.05). The TOx values were highest in the
      free TRAM flaps and were lower in decreasing order in the muscle-sparing TRAM,
      DIEP, and SIEA flaps (P > 0.05). The TOx values did not significantly correlate
      with vessel size, perforator number, or perforator row. Postoperative flap TOx
      was found to correlate with SO2 and was not significantly dependent on blood
      pressure, supplemental O2, or surgical variables. Careful interpretation of
      oximetry values is essential in decision making during postoperative flap
      monitoring.

PMID- 24934630
TI  - New autoinjector technology for the delivery of subcutaneous methotrexate in the
      treatment of rheumatoid arthritis.
AB  - Methotrexate (MTX) is the cornerstone of treatment for rheumatoid arthritis (RA),
      and is widely used both as first-line therapy and as an important component of
      long-term therapy. Although subcutaneous MTX is typically delivered orally,
      parenteral administration offers benefits with respect to tolerability and
      systemic exposure, and may be an underutilized treatment option. The RA patient
      population presents specific challenges for safe and accurate administration of
      parenteral therapies, because of common symptoms of joint pain and limited manual
      dexterity. These challenges may contribute to the low incidence of parenteral MTX
      administration. A novel MTX autoinjector (MTXAI) was recently introduced, which
      is designed to facilitate subcutaneous MTX self-administration among patients
      with RA. Here we review the development and utility of the MTXAI in the treatment
      of RA, and discuss how this technology may facilitate the use of subcutaneous
      MTX.

PMID- 24934631
TI  - Association between nocturnal blood pressure dipping and insulin resistance in
      children affected by NAFLD.
AB  - The aim of this study was to analyse the relationship between insulin-glucose
      metabolism, nocturnal blood pressure dipping and nonalcoholic fatty liver disease
      (NAFLD) in obese adolescents without diabetes. One hundred one consecutive
      children, with biopsy-proven NAFLD, were included in this study. Blood samples
      were drawn for the analyses of liver function tests, insulin-glucose metabolism
      and lipid profile appraisal. An ambulatory blood pressure measurement (ABPM) was
      performed. Seventy-six children (75.3 %) were systolic nondippers, and 23 of them
      were diastolic nondippers (30.3 %). No differences were found in the
      anthropometric parameters between the two groups. When compared to the systolic
      dippers, the systolic nondippers had higher medians of mean nocturnal blood
      pressure, glucose at 0, 60 and 120 min in the oral glucose tolerance test (OGTT),
      OGTT insulin at all time points and insulin-resistance values. No correlation of
      histopathological features with dipping/nondipping statuses was found.
      CONCLUSIONS: We found an association between a nocturnal blood pressure fall and
      measures of insulin levels, independent of obesity, or daytime blood pressure
      levels, among the obese patients with NAFLD. Although no association between
      nondipping profiles and NAFLD was observed in our study, further studies with a
      longer term follow-up are needed, to better elucidate the complex link between
      these particular entities.

PMID- 24934632
TI  - Livin is associated with the invasive and oncogenic phenotypes of human
      hepatocellular carcinoma cells.
AB  - AIM: Livin, a member of the inhibitors of apoptosis proteins, is expressed in
      variable cancers, and its expression is considered a poor prognostic marker. The
      aims of this study were to observe the effect of Livin on the behaviors of
      hepatocellular carcinoma (HCC) cells and to evaluate its expression in HCC
      tissues and its relation to prognosis. METHODS: The biological effects of Livin
      on tumor cell behavior were investigated using siRNA in HepG2 and Chang cells.
      Migration, invasion and proliferation assays were performed. Flow cytometric
      analyses and western blotting were used to evaluate the impact of Livin on
      apoptosis and the cell cycle. In addition, western blotting and
      immunohistochemistry were used to investigate Livin expression in HCC tissues.
      RESULTS: Livin knockdown suppressed tumor cell migration, invasion and
      proliferation in HCC cells, and increased the proportion of apoptotic cells as
      compared with scrambled siRNA-transfected HCC cells. Furthermore, Livin knockdown
      resulted in the activation of caspases and increased apoptosis. In addition,
      Livin knockdown modulated cell cycle regulatory protein levels such as decrease
      of cyclins and cyclin-dependent kinase (CDK) level, and increase of CDK inhibitor
      (CDKI) level in HCC cells. The Livin protein level was significantly elevated in
      HCC tissues as compared with normal hepatic tissues. However, Livin expression
      was not found to be associated with clinicopathological parameters, which
      included patient survival. CONCLUSION: These results suggest that Livin is
      associated with invasive and oncogenic phenotypes of human HCC cells.

PMID- 24934634
TI  - Characterisation and bioactivity of oosporein produced by endophytic fungus
      Cochliobolus kusanoi isolated from Nerium oleander L.
AB  - Bioactive compounds comprising secondary metabolites produced by endophytic fungi
      have wide applications in pharmacology and agriculture. Isolation,
      characterisation and evaluation of biological activities of secondary metabolites
      were carried out from Cochliobolus kusanoi an endophytic fungus of Nerium
      oleander L. The fungus was identified based on 18S rDNA sequence analysis. There
      are no reports available on the compounds of C.kusanoi hence, antimicrobial
      metabolite produced by this fungus was extracted and purified by fractionation
      using hexane, diethyl ether, dichloromethane, ethyl acetate and methanol. Out of
      all the solvent fractions, the methanol fraction exhibited better antimicrobial
      activity which was further purified and characterised as oosporein. Oosporein
      from C.kusanoi exhibited broad spectrum in vitro antimicrobial, antioxidant and
      cytotoxic activities. The characterisation and antioxidant activity of oosporein
      from C. kusanoi are reported for the first time. 

PMID- 24934635
TI  - No evidence for copy number and methylation variation in H19 and KCNQ10T1
      imprinting control regions in children born small for gestational age.
AB  - BACKGROUND: There is a substantial genetic component for birthweight variation,
      and although there are known associations between fetal genotype and birthweight,
      the role of common epigenetic variation in influencing the risk for small for
      gestational age (SGA) is unknown. The two imprinting control regions (ICRs)
      located on chromosome 11p15.5, involved in the overgrowth disorder Beckwith
      Wiedemann syndrome (BWS) and the growth restriction disorder Silver-Russell
      syndrome (SRS), are prime epigenetic candidates for regulating fetal growth. We
      investigated whether common variation in copy number in the BWS/SRS 11p15 region
      or altered methylation levels at IGF2/H19 ICR or KCNQ10T1 ICR was associated with
      SGA. METHODS: We used a methylation-specific multiplex-ligation-dependent probe
      amplification assay to analyse copy number variation in the 11p15 region and
      methylation of IGF2/H19 and KCNQ10T1 ICRs in blood samples from 153 children
      (including 80 SGA), as well as bisulfite pyrosequencing to measure methylation at
      IGF2 differentially methylated region (DMR)0 and H19 DMR. RESULTS: No copy number
      variants were detected in the analyzed cohort. Children born SGA had 2.7% lower
      methylation at the IGF2 DMR0. No methylation differences were detected at the H19
      or KCNQ10T1 DMRs. CONCLUSIONS: We confirm that a small hypomethylation of the
      IGF2 DMR0 is detected in peripheral blood leucocytes of children born SGA at
      term. Copy number variation within the 11p15 BWS/SRS region is not an important
      cause of non-syndromic SGA at term.

PMID- 24934636
TI  - Online GESS: prediction of miRNA-like off-target effects in large-scale RNAi
      screen data by seed region analysis.
AB  - BACKGROUND: RNA interference (RNAi) is an effective and important tool used to
      study gene function. For large-scale screens, RNAi is used to systematically down
      regulate genes of interest and analyze their roles in a biological process.
      However, RNAi is associated with off-target effects (OTEs), including microRNA
      (miRNA)-like OTEs. The contribution of reagent-specific OTEs to RNAi screen data
      sets can be significant. In addition, the post-screen validation process is time
      and labor intensive. Thus, the availability of robust approaches to identify
      candidate off-targeted transcripts would be beneficial. RESULTS: Significant
      efforts have been made to eliminate false positive results attributable to
      sequence-specific OTEs associated with RNAi. These approaches have included
      improved algorithms for RNAi reagent design, incorporation of chemical
      modifications into siRNAs, and the use of various bioinformatics strategies to
      identify possible OTEs in screen results. Genome-wide Enrichment of Seed Sequence
      matches (GESS) was developed to identify potential off-targeted transcripts in
      large-scale screen data by seed-region analysis. Here, we introduce a user
      friendly web application that provides researchers a relatively quick and easy
      way to perform GESS analysis on data from human or mouse cell-based screens using
      short interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), as well as for
      Drosophila screens using shRNAs. Online GESS relies on up-to-date transcript
      sequence annotations for human and mouse genes extracted from NCBI Reference
      Sequence (RefSeq) and Drosophila genes from FlyBase. The tool also accommodates
      analysis with user-provided reference sequence files. CONCLUSION: Online GESS
      provides a straightforward user interface for genome-wide seed region analysis
      for human, mouse and Drosophila RNAi screen data. With the tool, users can either
      use a built-in database or provide a database of transcripts for analysis. This
      makes it possible to analyze RNAi data from any organism for which the user can
      provide transcript sequences.

PMID- 24934638
TI  - Strategies for fertility preservation in young early breast cancer patients.
AB  - Diagnosis of breast cancer in young women poses a threat to fertility. Due to a
      recent trend of delaying pregnancy, an increasing number of breast cancer
      patients in reproductive age wish to bear children. Health care providers have
      the responsibility to know how to manage fertility issues in cancer survivors.
      Oncofertility counseling is of great importance to many young women diagnosed
      with cancer and should be managed in a multi-disciplinary background. Most of
      young breast cancer patients are candidate to receive chemotherapy, which could
      lead to premature ovarian failure. A baseline evaluation of ovarian reserve may
      help in considering the different fertility preservation options. The choice of
      the suitable strategy depends also on age, type of chemotherapy, partner status
      and patients' motivation. Various options are available, some established such as
      embryo and oocyte cryopreservation, some still experimental such as ovarian
      tissue cryopreservation and ovarian suppression with GnRHa during chemotherapy.
      An early referral to a reproductive specialist should be offered to patients at
      risk of infertility who are interested in fertility preservation. 

PMID- 24934637
TI  - Long term survival of HER2-positive early breast cancer treated with trastuzumab
      based adjuvant regimen: a large cohort study from clinical practice.
AB  - Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early
      breast cancer significantly prolonged overall survival (OS) and disease free
      survival (DFS) in large randomized trials, with sustained benefits at four-year
      follow-up. We assessed long-term survival estimates and predictors in a large
      cohort of Italian women with early breast cancer treated with trastuzumab in
      clinical practice. Through a record linkage between five regional healthcare
      databases, we identified women treated with trastuzumab for early breast cancer
      in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method,
      and independent predictors were assessed using proportional hazard models. 2046
      women received trastuzumab in early breast cancer adjuvant setting. Overall, the
      proportion of patients surviving free of disease was 93.9% at one year, 85.8% at
      2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%,
      91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent
      predictors of worse survival outcomes were age <40 or >=70 years compared to age
      40-69 years, positive nodal status, radical breast surgery, combination therapy
      with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular
      disease), and a trastuzumab-based regimen lasting less than six months. Long term
      survival rates of women treated with trastuzumab for early breast cancer in
      clinical practice were consistent with estimates from clinical trials testing the
      drug in the adjuvant setting. 

PMID- 24934640
TI  - Center-defined unacceptable HLA antigens facilitate transplants for sensitized
      patients in a multi-center kidney exchange program.
AB  - Multi-center kidney paired donation (KPD) is an exciting new transplant option
      that has not yet approached its full potential. One barrier to progress is
      accurate virtual crossmatching for KPD waitlists with many highly sensitized
      patients. Virtual crossmatch results from a large multi-center consortium, the
      National Kidney Registry (NKR), were analyzed to determine the effectiveness of
      flexible center-specific criteria for virtual crossmatching. Approximately two
      thirds of the patients on the NKR waitlist are highly sensitized (>80% CPRA).
      These patients have antibodies against HLA-A (63%), HLA-B (66%), HLA-C (41%), HLA
      DRB1 (60%), HLA-DRB3/4/5 (18-22%), HLA-DQB1 (54%) and HLA-DPB1 (26%). With donors
      typed for these loci before activation, 91% of virtual crossmatches accurately
      predicted an acceptable cell-based donor crossmatch. Failed virtual crossmatches
      were attributed to equivocal virtual crossmatches (46%), changes in HLA
      antibodies (21%), antibodies against HLA-DQA (6%), transcription errors (6%),
      suspected non-HLA antibodies (5%), allele-specific antibodies (1%) and unknown
      causes (15%). Some failed crossmatches could be prevented by modifiable factors
      such as more frequent assessment of HLA antibodies, DQA1 typing of donors and
      auditing data entry. Importantly, when transplant centers have flexibility to
      define crossmatch criteria, it is currently feasible to use virtual crossmatching
      for highly sensitized patients to reliably predict acceptable cell-based
      crossmatches. 

PMID- 24934639
TI  - Comparison of Profiles of Perioperative Serum C-Reactive Protein Levels in
      Neonates Undergoing the Norwood Procedure or Arterial Switch Operation.
AB  - OBJECTIVES: Serum C-reactive protein (CRP) is a marker of systemic inflammatory
      response induced by cardiopulmonary bypass (CPB). Neonates undergoing the Norwood
      procedure (NP) have a poorer systemic oxygen transport status than those after
      other CPB surgeries. We compared the perioperative CRP in neonates undergoing NP
      or arterial switch operation (ASO). METHODS: Data obtained prior to and within
      postoperative day (POD) 15 from 64 neonates in NP group and 47 in ASO group.
      Plasma CRP, white blood cells, doses of inotropes and steroid, cultures of blood
      and body fluids were recorded simultaneously. Demographic data included the
      durations of CPB, aortic cross clamp (ACC) and circulatory arrest, intensive care
      unit and hospital stay, and death. RESULTS: NP group had a shorter CPB and ACC
      but a longer circulatory arrest than ASO group. CRP was higher preoperatively in
      NP group than ASO group (21 +/- 24 vs.13 +/- 26 mg/L, P = 0.01). CRP increased to
      80 +/- 48 mg/L after NP and 73 +/- 36 mg/L after ASO on POD1-2, and then
      gradually decreased to 51 +/- 35 mg/L in NP group and to 43 +/- 46 mg/L in ASO
      group by POD-15. Throughout the postoperative period, CRP, as well as lactate,
      was significantly higher in NP group than ASO group (P = 0.04 and 0.003,
      respectively). CRP correlated positively with neutrophil count and negatively
      with lymphocyte count, CPB duration, and doses of hydrocortisone. CONCLUSIONS:
      Neonates undergoing NP have a higher level of serum CRP, reflecting a greater
      systemic inflammatory response before and after CPB than those undergoing ASO,
      despite of shorter CPB and ACC. The higher level of serum CRP was associated with
      a significantly higher level of arterial lactate in the NP group than in the ASO
      group. This may suggest an important role of systemic oxygen transport in
      systemic inflammatory response in addition to CPB in neonates with congenital
      heart defects.

PMID- 24934641
TI  - Assessment of motor function of the remnant stomach by 13C breath test with
      special reference to gastric local resection.
AB  - BACKGROUND: Indications for gastric local resection (LR) include gastrointestinal
      stromal tumors, neuroendocrine tumors, and early gastric cancer. LR is expected
      to preserve physiological function and ameliorate postgastrectomy syndrome.
      METHODS: Gastric emptying was assessed by the (13)C-acetate breath test in 20
      healthy volunteers (HVs) and 60 gastrectomized patients [distal gastrectomy with
      Billroth I reconstruction (DGBI) in 26 patients, LR in 34 patients]. For the
      (13)C breath test, 100 mg of (13)C-acetate sodium salt was mixed in a test meal.
      Breath samples were collected before intake and during the next 3 h. We compared
      the gastric reservoir capacity using the gastric retention rate at 5 min (RR5)
      and gastric emptying by the half emptying time (T1/2). Patients completed a
      questionnaire survey about their symptoms, dietary intake, body weight, and
      restriction of activities of daily living [reflecting quality of life (QOL)].
      RESULTS: The RR5 values for the HV, LR, and DGBI groups were 93.7, 90.0, and
      45.3* %, respectively (*compared to HV and LR, p < 0.0001). The T1/2 values were
      23.3, 20.2, and 5.9* min, respectively. Dietary intake and body weight change
      were significantly more reduced in the DGBI group than the LR group (p < 0.05).
      Subgroup analysis indicated that the reservoir capacity in those with LR at the
      lesser curvature was more disturbed than that in patients with LR at the greater
      curvature. The questionnaire showed no differences in those patients' QOL.
      CONCLUSIONS: Because the reservoir capacity, the gastric emptying and QOL were
      maintained, LR is an option for selected patients with early gastric cancer.

PMID- 24934642
TI  - A six-step protocol to systematic process evaluation of multicomponent cluster
      randomised health promoting interventions illustrated by the Boost study.
AB  - BACKGROUND: In multicomponent interventions it is important to examine the
      implementation of each component to enable valid assessments of the effectiveness
      of each component. Many studies do not systematically document, evaluate and
      report the level of implementation and there is a lack of systematic approaches
      to conduct process evaluation studies to guide researchers and evaluators. The
      aim of this study was to present a systematic approach to plan process evaluation
      of the implementation of randomised multicomponent interventions. METHODS:
      Building on existing process evaluation frameworks and concepts, we developed a
      six-step protocol: 1. Brainstorm of processes necessary for full implementation
      and potential barriers and facilitators to implementation; 2. Application of
      process evaluation concepts to ensure inclusion of important implementation
      processes; 3. Measurement of proximal outcomes; 4. Identification of relevant
      data sources; 5. Selection of methods and timing of data collection of process
      measures; 6. Development of instruments. The protocol was applied to the Boost
      study, a multicomponent school-based dietary intervention. RESULTS AND
      CONCLUSIONS: The protocol was readily applicable for planning process evaluation
      of environmental and educational intervention components in a school setting. The
      protocol ensures systematic assessment of the implementation processes that are
      crucial for interpretation of intervention effects. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN11666034.

PMID- 24934643
TI  - Spectrum of the mutations in Bernard-Soulier syndrome.
AB  - Bernard-Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder
      characterized by defects of the GPIb-IX-V complex, a platelet receptor for von
      Willebrand factor (VWF). Most of the mutations identified in the genes encoding
      for the GP1BA (GPIbalpha), GP1BB (GPIbbeta), and GP9 (GPIX) subunits prevent
      expression of the complex at the platelet membrane or more rarely its interaction
      with VWF. As a consequence, platelets are unable to adhere to the vascular
      subendothelium and agglutinate in response to ristocetin. In order to collect
      information on BSS patients, we established an International Consortium for the
      study of BSS, allowing us to enrol and genotype 132 families (56 previously
      unreported). With 79 additional families for which molecular data were gleaned
      from the literature, the 211 families characterized so far have mutations in the
      GP1BA (28%), GP1BB (28%), or GP9 (44%) genes. There is a wide spectrum of
      mutations with 112 different variants, including 22 novel alterations. Consistent
      with the rarity of the disease, 85% of the probands carry homozygous mutations
      with evidence of founder effects in some geographical areas. This overview
      provides the first global picture of the molecular basis of BSS and will lead to
      improve patient diagnosis and management. 

PMID- 24934644
TI  - Mechanistic insights into response of Staphylococcus aureus to bioelectric effect
      on polypyrrole/chitosan film.
AB  - Treatment of biofilm-related infections in orthopedics remains a serious clinical
      challenge. It is known that an electric current can significantly enhance the
      potency of some antibiotics against biofilms (bioelectric effect) but the
      uncertainty of the mechanisms and the electrolytic cell-like system used in
      previous studies limit its applications. Herein, the behavior of Staphylococcus
      aureus (S. aureus) on an electrically conductive polypyrrole/chitosan film upon
      passage of a direct current (DC) through the film was investigated in the absence
      and presence of gentamicin. The killing efficacy of the bacteria within the
      biofilm by gentamicin was greatly enhanced by the DC treatment. From an analysis
      of the gene expression by the biofilm bacteria after treatment with gentamicin,
      DC and their combination, it is postulated that the promotion of bacterial
      autolysis by DC treatment is responsible for the enhanced susceptibility of
      biofilm S. aureus to gentamicin. This postulate is supported by an increase in
      the amount of extracellular deoxyribonucleic acid and adenosine triphosphate, and
      the appearance of disrupted bacterial cells in the biofilm after DC treatment.
      These findings provide a new insight into the interaction between DC and
      bacteria, and offer potential benefits for the treatment of infections in
      orthopedics. 

PMID- 24934645
TI  - Doxorubicin loaded singlet-oxygen producible polymeric micelle based on chlorine
      e6 conjugated pluronic F127 for overcoming drug resistance in cancer.
AB  - Drug resistance remains one of the primary obstacles to the success of cancer
      chemotherapy. In this work, we demonstrate a singlet-oxygen producible polymeric
      (SOPP) micelle based on photosensitizer (PS, chlorin e6 (Ce6)) conjugated
      amphiphilic copolymer (pluronic F127((r)), PF127) for overcoming drug resistance
      in cancer by applying photochemical internalization (PCI). The doxorubicin (DOX)
      loaded SOPP micelles were self-assembled from Ce6-PF127 conjugates, which have a
      spherical shape with a uniform size of ~30 nm. Compared with free Ce6, enhanced
      singlet-oxygen generation efficiency in the DOX-loaded SOPP micelles have been
      demonstrated in aqueous environments due to their increased water-dispersibility.
      Under low dose of laser power and anti-cancer drug (DOX) conditions, in vitro and
      in vivo studies on drug-resistant cancer cells demonstrated that singlet-oxygen
      mediated cellular membrane damage (caused by lipid peroxidation) significantly
      increased the cellular uptake of drug (DOX), which led to overcoming the drug
      resistance in cancer cells without undesirable side effects. We believe this
      approach could represent a promising platform for drug-resistant cancer
      treatment. 

PMID- 24934646
TI  - Effectiveness of lifestyle change plus dental care (LCDC) program on improving
      glycemic and periodontal status in the elderly with type 2 diabetes.
AB  - BACKGROUND: Currently, there is an increased prevalence of diabetes mellitus
      among the elderly. To minimize adverse effects on glycemic control, prevention
      and management of general and oral complications in diabetic patients is
      essential. The purpose of the present study is to assess the effectiveness of a
      Lifestyle Change plus Dental Care (LCDC) program to improve glycemic and
      periodontal status in the elderly with type 2 diabetes. METHODS: A quasi
      experimental study was conducted in Health Centers 54 (intervention) and 59
      (control) from October 2013 to January 2014. 66 diabetic patients per health
      center were included. At baseline, the intervention group attended a 20 minute
      lifestyle and oral health education program, individual lifestyle counseling
      using motivational interviewing (MI), application of self regulation manual, and
      individual oral hygiene instruction. The intervention group received booster
      education every visit by viewing a 15 minute educational video. The control group
      received a routine program. Participants were assessed at baseline and 3 month
      follow up for glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), body
      mass index (BMI), periodontal status, knowledge, attitude and practice of oral
      health and diabetes mellitus. Data were analyzed by using descriptive statistic,
      Chi-square test, Fisher's exact test, t-test, and multiple linear regression.
      RESULTS: After the 3 month follow up, a multiple linear regression analysis
      showed that the intervention group was significantly negatively correlated in
      both glycemic and periodontal status. Participants in the intervention group had
      significantly lower glycosylated hemoglobin (HbA1c), fasting plasma glucose
      (FPG), plaque index score, gingival index score, pocket depth, clinical
      attachment level (CAL), and percentage of bleeding on probing (BOP) when compared
      to the control group. CONCLUSIONS: The combination of lifestyle change and dental
      care in one program improved both glycemic and periodontal status in the elderly
      with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.in.th: TCTR20140602001.

PMID- 24934647
TI  - Cellular signaling in the aging immune system.
AB  - Causes for immunosenescence and inflamm-aging have to be established. Efficient
      function of the immune system requires homeostatic regulation from receptor
      recognition of antigenic challenge to cell responses and adaptation to its
      changing environment. It is reasonable to assume that one of the most important
      molecular causes of immunosenescence is alteration in the regulation of signaling
      pathways. Indeed, alterations in feed-forward and negative feedback (inhibitory)
      signaling have been highlighted in all cells involved in the immune response
      including short-lived (neutrophils) and long-lived (T lymphocytes) cells. These
      dysregulations tip the balance in favor of altered (less efficient) function of
      the immune system. In this review, we summarize our knowledge on signal
      transduction changes in the aging immune system and propose a unifying mechanism
      as one of the causes of immunosenescence. Modulation of these pathways with aging
      represents a major challenge to restore the immune response to functional levels.

PMID- 24934649
TI  - Etiology of fatal community-acquired pneumonia in children.

PMID- 24934650
TI  - A long-term static immersion experiment on the leaching behavior of heavy metals
      from waste printed circuit boards.
AB  - Printed circuit boards (PCBs) are the main components of electrical and
      electronic equipment (EEE). Waste PCBs contain several kinds of heavy metals,
      including Cu, Pb and Zn. We characterize the leaching of heavy metals (Cu, Pb, Zn
      and Ni) from waste PCBs in a pH range of 3.0 to 5.6 using a novel approach based
      on batch pH-static leaching experiments in this work. The results indicate that
      the leaching behavior of Cu, Pb, Zn and Ni is strongly dependent on pH. Leaching
      behavior also varies with different pH values and leaching times. The maximum
      concentrations of Cu, Pb, Zn and Ni in leachate from waste PCBs were 335.00,
      17.57, 2.40 and 2.33 mg L(-1), respectively. The highest Pb, Ni, and Cu
      concentrations leached significantly exceeded the European Union waste-acceptance
      limit values with respect to inert waste landfills. The leaching of metals
      follows the shrinking core model with surface reaction control.

PMID- 24934648
TI  - B cell function and influenza vaccine responses in healthy aging and disease.
AB  - Influenza vaccination is less effective in elderly as compared to young
      individuals. Several studies have addressed the identification of immune
      biomarkers able to monitor or predict a protective humoral immune response to the
      vaccine. In this review, we summarize these data, with emphasis on the effects of
      aging on influenza vaccine-specific B cell responses in healthy individuals and
      patients with Type-2 Diabetes, HIV and cardiovascular diseases. 

PMID- 24934651
TI  - Sexual risk behavior, alcohol use, and social media use among secondary school
      students in informal settlements in Cape Town and Port Elizabeth, South Africa.
AB  - South Africa's HIV prevalence among young people remains among the highest in the
      world. A cross-sectional study was carried out in 2012 to estimate prevalences of
      sexual risk behavior and hazardous alcohol use (HAU) (via the Alcohol Use
      Disorder Identification Test) as well as to investigate potential associations
      between these outcomes and social media use. In all, 4485 students (mean age
      15.66 years, SD 1.39) at 46 secondary schools in informal settlements in Cape
      Town and Port Elizabeth completed mobile-phone-assisted, self-administered
      baseline questionnaires within a cluster-randomized trial. In all, 312 females
      (12.5 %) and 468 males (23.5 %) screened positive for HAU (AOR = 1.98, 95 % CI
      1.69-2.34). 730 males (39.9 %) and 268 females (11.8 %) reported having had two
      or more partners in the last year (AOR = 3.46, 95 % CI 2.87-4.16). Among females,
      having a Facebook account was associated with reported multiple partnerships in
      the last year (AOR = 1.81, 95 % CI 1.19-2.74), age-disparate sex in the last year
      (AOR = 1.96, 95 % CI 1.16-3.32) and HAU (AOR = 1.97, 95 % CI 1.41-2.74). Using
      Mxit-a popular mobile instant messaging application-was associated with higher
      odds of reported multiple partnerships in the last year among both males (AOR =
      1.70, 95 % CI 1.35-2.14) and females (AOR = 1.45, 95 % CI 1.07-1.96) and with HAU
      among both males (AOR = 1.47, 95 % CI 1.14-1.90) and females (AOR = 1.50, 95 % CI
      1.18-1.90). Further longitudinal and qualitative research should explore in more
      depth the observed links between social media and risk behavior. 

PMID- 24934652
TI  - Experiences of violence and association with decreased drug abstinence among
      women in Cape Town, South Africa.
AB  - Drug abuse is a contributing factor in women's HIV risk in low-income communities
      in Cape Town, South Africa. This study assessed whether experiencing violence is
      associated with reduced drug abstinence among adult women (n = 603) participating
      in a randomized field trial for an HIV prevention study in Cape Town. In relation
      to drug abstinence at 12-month follow-up, multivariable regression models were
      used to assess (1) baseline partner and non-partner victimization, and (2)
      victimization at 12-month follow-up among participants reporting baseline
      victimization. Baseline partner (AOR = 0.6; 95 % CI 0.4-0.9) and non-partner
      victimization (AOR = 0.6; 95 % CI 0.4-0.9) were associated with a reduced
      likelihood of drug abstinence at follow-up. Among participants who reported
      victimization at baseline, those no longer reporting victimization at follow-up
      did not differ significantly in drug abstinence compared with those who reported
      victimization at follow-up. The study findings highlight the lasting impact of
      victimization on women's drug use outcomes, persisting regardless of whether
      violence was no longer reported at follow-up. Overall, the findings support the
      need for the primary prevention of violence to address the cycle of violence,
      drug use, and HIV among women in this setting.

PMID- 24934653
TI  - A putative soybean GmsSOS1 confers enhanced salt tolerance to transgenic
      Arabidopsis sos1-1 mutant.
AB  - The cDNA of GmsSOS1, a putative plasma membrane Na(+)/H(+) antiporter gene
      isolated from Glycine max, Glycine soja, and their hybrid, was constructed into
      plant expression vector pCAMBIA 1300 and then transformed with Agrobacterium
      tumefaciens under the control of CaMV 35S promoter to Arabidopsis thaliana wild
      type (WT) and mutant (atsos1-1) plants. By hygromycin resistance detection and
      PCR analysis, transgenic plants (WT35S:GmsSOS1 and atsos1-1 35S:GmsSOS1) were
      obtained. Seed germination, seedling growth, and Na(+) contents in roots and
      shoots were analytically compared among WT, atsos1-1 mutant, and their transgenic
      lines under salt stress. The results showed that when GmsSOS1 was integrated into
      the genome of A. thaliana, the inhibitions of salt stress on seed germination and
      seedling growth were all significantly improved, and enhanced salt tolerance was
      displayed, which may be attributed to the decrease of Na(+) absorption in roots
      and transportation in shoots of the transgenic lines, especially for that of
      atsos1-1 mutant. 

PMID- 24934654
TI  - Identification of inhibitors of Plasmodium falciparum RuvB1 helicase using
      biochemical assays.
AB  - Human malaria is a major parasitic infection, and the situation has worsened
      mainly due to the emergence of resistant malaria parasites to several anti
      malarial drugs. Thus, an urgent need to find suitable drug targets has led to the
      development of newer classes of anti-malarial drugs. Helicases have been targeted
      to develop therapeutics for viral, bacterial, and other microorganism infections.
      Recently, Plasmodium falciparum RuvB ATPases/helicases have been characterized
      and proposed as a suitable antimalarial drug target. In the present study, the
      screening of various compounds was done and the results suggest that PfRuvB1
      ATPase activity is inhibited considerably by the novobiocin and partially by
      cisplatin and ciprofloxacin. Helicase assay of PfRuvB1 in the presence of various
      compounds suggest novobiocin, actinomycin, and ethidium bromide as potent
      inhibitors. Novobiocin inhibits the helicase activity of PfRuvB1 possibly by
      blocking the ATPase activity of PfRuvB1. This study is unique in respect to the
      identification of novobiocin as inhibitor of PfRuvB1, partially by competing with
      ATP binding at its active site and provides evidence for PfRuvB1 as target of
      novobiocin after DNA gyrase-B and HSP90. These studies will certainly help the
      pharmacologist to design and develop some novel inhibitor specific to PfRuvB1,
      which may serve as suitable chemotherapeutics to target malaria. 

PMID- 24934656
TI  - New perspectives in the management of basal cell carcinoma.

PMID- 24934657
TI  - Access to institutional delivery care and reasons for home delivery in three
      districts of Tanzania.
AB  - INTRODUCTION: Globally, health facility delivery is encouraged as a single most
      important strategy in preventing maternal and neonatal morbidity and mortality.
      However, access to facility-based delivery care remains low in many less
      developed countries. This study assesses facilitators and barriers to
      institutional delivery in three districts of Tanzania. METHODS: Data come from a
      cross-sectional survey of random households on health behaviours and service
      utilization patterns among women and children aged less than 5 years. The survey
      was conducted in 2011 in Rufiji, Kilombero, and Ulanga districts of Tanzania,
      using a closed-ended questionnaire. This analysis focuses on 915 women of
      reproductive age who had given birth in the two years prior to the survey. Chi
      square test was used to test for associations in the bivariate analysis and
      multivariate logistic regression was used to examine factors that influence
      institutional delivery. RESULTS: Overall, 74.5% of the 915 women delivered at
      health facilities in the two years prior to the survey. Multivariate analysis
      showed that the better the quality of antenatal care (ANC) the higher the odds of
      institutional delivery. Similarly, better socioeconomic status was associated
      with an increase in the odds of institutional delivery. Women of Sukuma ethnic
      background were less likely to deliver at health facilities than others. Presence
      of couple discussion on family planning matters was associated with higher odds
      of institutional delivery. CONCLUSION: Institutional delivery in Rufiji,
      Kilombero, and Ulanga district of Tanzania is relatively high and significantly
      dependent on the quality of ANC, better socioeconomic status as well as between
      partner communication about family planning. Therefore, improving the quality of
      ANC, socioeconomic empowerment as well as promoting and supporting inter-spousal
      discussion on family planning matters is likely to enhance institutional
      delivery. Programs should also target women from the Sukuma ethnic group towards
      universal access to institutional delivery care in the study area.

PMID- 24934658
TI  - Challenging the gold standard for 3D-QSAR: template CoMFA versus X-ray alignment.
AB  - X-ray-based alignments of bioactive compounds are commonly used to correlate
      structural changes with changes in potencies, ultimately leading to three
      dimensional quantitative structure-activity relationships such as CoMFA or CoMSIA
      models that can provide further guidance for the design of new compounds. We have
      analyzed data sets where the alignment of the compounds is entirely based on
      experimentally derived ligand poses from X-ray-crystallography. We developed
      CoMFA and CoMSIA models from these X-ray-determined receptor-bound conformations
      and compared the results with models generated from ligand-centric Template
      CoMFA, finding that the fluctuations in the positions and conformations of
      compounds dominate X-ray-based alignments can yield poorer predictions than those
      from the self-consistent template CoMFA alignments. Also, when there exist
      multiple different binding modes, structural interpretation in terms of binding
      site constraints can often be simpler with template-based alignments than with X
      ray-based alignments. 

PMID- 24934659
TI  - Cymbopogon martinii essential oil and geraniol at noncytotoxic concentrations
      exerted immunomodulatory/anti-inflammatory effects in human monocytes.
AB  - OBJECTIVES: In traditional medicine, plants have formed the basis of
      sophisticated systems that have been in existence for thousands of years and
      still provide mankind with new remedies. Cymbopogon martinii, known as palmarosa,
      has been used in aromatherapy as a skin tonic due to its antimicrobial
      properties. It has also used in Ayurvedic medicine for skin problems and to
      relieve nerve pain. The immunomodulatory action of C. martinii essential oil (EO)
      and geraniol was evaluated regarding the production of pro- and anti-inflammatory
      cytokines (tumour necrosis factor (TNF)-alpha and IL-10, respectively) by human
      monocytes in vitro. METHODS: Monocyte cultures were incubated with EO or
      geraniol. After 18 h, cytotoxicity assays were performed using 3-(4,5-dimethyl
      thiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and cytokine production was
      determined by ELISA. KEY FINDINGS: The variables showed no cytotoxic effects on
      monocytes. TNF-alpha production was not affected by C. martinii and geraniol, and
      only the concentration of 5 MUg/ml of C. martinii stimulated its production. On
      the other hand, all concentrations of C. martinii and geraniol increased IL-10
      production by human monocytes. CONCLUSIONS: Data showed that noncytotoxic
      concentrations of EO and geraniol exerted an anti-inflammatory action by
      increasing IL-10 production; moreover, geraniol seemed to be probably responsible
      for EO immunomodulatory activity in our assay condition.

PMID- 24934660
TI  - A novel model for Ki67 assessment in breast cancer.
AB  - BACKGROUND: Ki67 is currently the proliferation biomarker of choice, with both
      prognostic and predictive value in breast cancer. A lack of consensus regarding
      Ki67 use in pre-analytical, analytical and post-analytical practice may hinder
      its formal acceptance in the clinical setting. METHODS: One hundred breast cancer
      samples were stained for Ki67. A standard estimation of Ki67 using fixed
      denominators of 200, 400 and 1 000 counted tumor cells was performed, and a cut
      off at 20% was applied, Ki67static. A novel stepwise counting strategy for Ki67
      estimation, Ki67scs, was developed based on rejection regions derived from exact
      two-sided binomial confidence intervals for proportions. Ki67scs was defined by
      the following parameters: the cut-off (20%), minimum (50) and maximum (400)
      number of tumor cells to count, increment (10) and overall significance level of
      the test procedure (0.05). Results from Ki67scs were compared to results from the
      Ki67static estimation with fixed denominators. RESULTS: For Ki67scs, the median
      number of tumor cells needed to determine Ki67 status was 100; the average, 175.
      Among 38 highly proliferative samples, the average Ki67scs fraction was 45%. For
      these samples, the fraction decreased from 39% to 37% to 35% with static counting
      of 200, 400 and 1 000 cells, respectively. The largest absolute difference
      between the estimation methods was 23% (42% (Ki67scs) vs. 19% (Ki67static)) and
      resulted in an altered sample classification. Among the 82 unequivocal samples,
      74 samples received the same classification using both Ki67scs and Ki67static. Of
      the eight disparate samples, seven were classified highly proliferative by
      Ki67static when 200 cells were counted; whereas all eight cases were classified
      as low proliferative when 1 000 cells were counted. CONCLUSIONS: Ki67 estimation
      using fixed denominators may be inadequate, particularly for tumors demonstrating
      extensive heterogeneity. We propose a time saving stepwise counting strategy,
      which acknowledges small highly proliferative hot spots. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3588156111195336.

PMID- 24934661
TI  - A novel high-speed imaging technique to predict the macroscopic spray
      characteristics of solution based pressurised metered dose inhalers.
AB  - PURPOSE: Non-volatile agents such as glycerol are being introduced into solution
      based pMDI formulations in order to control mean precipitant droplet size. To
      assess their biopharmaceutical efficacy, both microscopic and macroscopic
      characteristics of the plume must be known, including the effects of external
      factors such as the flow generated by the patient's inhalation. We test the
      hypothesis that the macroscopic properties (e.g. spray geometry) of a pMDI spray
      can be predicted using a self-similarity model, avoiding the need for repeated
      testing. METHODS: Glycerol-containing and glycerol-free pMDI formulations with
      matched mass median aerodynamic diameters are investigated. High-speed schlieren
      imaging is used to extract time-resolved velocity, penetration and spreading
      angle measurements of the pMDI spray plume. The experimental data are used to
      validate the analytical model. RESULTS: The pMDI spray develops in a manner
      characteristic of a fully-developed steady turbulent jet, supporting the
      hypothesis. Equivalent glycerol-containing and non glycerol-containing
      formulations exhibit similar non-dimensional growth rates and follow a self
      similar scaling behaviour over a range of physiologically relevant co-flow rates.
      CONCLUSIONS: Using the proposed model, the mean leading edge penetration,
      velocity and spreading rate of a pMDI spray may be estimated a priori for any co
      flow conditions. The effects of different formulations are captured in two
      scaling constants. This allows formulators to predict the effects of variation
      between pMDIs without the need for repeated testing. Ultimately, this approach
      will allow pharmaceutical scientists to rapidly test a number of variables during
      pMDI development.

PMID- 24934662
TI  - Aerosolized montelukast polymeric particles-an alternative to oral montelukast
      alleviate symptoms of asthma in a rodent model.
AB  - PURPOSE: Cysteinyl leukotrienes (CysLTs) propagate inflammatory reactions that
      result from allergen exposure in asthma. Montelukast, a CysLT type-1 receptor
      antagonist, disrupts mediator-receptor interactions and minimizes inflammatory
      response. In this study, we have evaluated anti-asthmatic efficacy of inhalable
      montelukast-loaded large porous particulate formulations in ovalbumin-induced rat
      airway inflammation model that mimics asthma. METHODS: The anti-inflammatory
      effects of a montelukast-loaded formulation were investigated in rats by
      measuring the total protein content, levels of injury markers and number of
      inflammatory cells in the bronchoalveolar lavage fluid (BALF). The
      histopathological studies assessed the morphological and structural changes that
      occur in asthmatic lungs. Animals were also challenged with methacholine to
      examine the airway hyper-reactivity. RESULTS: Compared with healthy animals,
      asthmatic animals showed a 3.8- and 4.77-fold increase in the protein content and
      number of inflammatory cells in BALF, respectively. Intratracheal montelukast
      particles reduced the protein content by 3.3-fold and the number of inflammatory
      cells by 2.62-fold. Also, montelukast particles reduced the lactate dehydrogenase
      (LDH) and myeloperoxidase (MPO) levels by a 4.87- and 6.8-fold in BALF,
      respectively. Montelukast particles reduced the airway wall thickness by 2.5-fold
      compared with untreated asthmatic lungs. Further, particulate formulation
      protected the lungs against methacholine-induced bronchial provocation (p <
      0.05). CONCLUSIONS: Respirable large porous particles containing montelukast
      alleviated allergen-induced inflammatory response in an animal model and
      prevented histological changes associated with asthma. Thus montelukast-loaded
      large porous polylactic acid (PLA) particles could be an aerosolized delivery
      approach for administration of currently available oral montelukast.

PMID- 24934663
TI  - Prevention of biofilm formation by methacrylate-based copolymer films loaded with
      rifampin, clarithromycin, doxycycline alone or in combination.
AB  - PURPOSE: This study reports the incorporation of the antibiotics rifampin,
      doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and
      their effect on biofilm prevention. BACKGROUND: Invasive procedures in patients
      such as surgical device, or intravenous or urinary catheter implantation, often
      results in complicated hospital-acquired nosocomial infections. Biofilm formation
      is essential to establish these infections on these devices and novel antibiotic
      delivery approaches are needed for more effective management. METHODS: The films
      were evaluated in vitro for drug release and for their ability to prevent biofilm
      formation by methicillin susceptible and methicillin resistant Staphylococcus
      aureus. Surface tension components, obtained from contact angle measurements, and
      the morphology of the films evaluated by scanning electron microscopy were also
      investigated. RESULTS: In this study, antibiotic-loaded methacrylic copolymer
      films that effectively released rifampin, clarithromycin and doxycycline for up
      to 21 days prevented biofilm formation when tested in an in vitro bioreactor
      model. These drug loaded copolymer films provided the advantage by coating
      materials with a novel surface that was unsuitable for resettling of biofilms
      once the antibiotic was dissolved from the polymer surface. A combination of
      rifampin and clarithromycin released from the polymer film provided >99.9% kill
      of an MRSA inoculate for up to 72 h. CONCLUSION: Results showed that combining
      multiple drugs in copolymer films with unique surface properties, initial
      hydrophilicity and increase in roughness, can be an effective way to prevent
      biofilm formation.

PMID- 24934664
TI  - Enhanced association of probucol with chylomicron by pharmaceutical excipients:
      an in vitro study.
AB  - In this study, we examined the effect of pharmaceutical excipients preferred in
      lipid-based formulations for lymphatic delivery on in vitro association of
      probucol with chylomicron (CM). CM stability study was performed under the
      conditions of room temperature, refrigeration and deep freezing to optimize the
      storage condition of CM dispersion prior to CM-binding study. The mean particle
      size, size distribution and zeta potential value were considerably maintained for
      48 h under the refrigeration condition. CM-binding study was conducted using
      probucol incorporated in vehicles composed of solubilizer (Transcutol HP or
      ethanol or propylene glycol) or surfactant (Tween-80 or Tween-20 or Cremophor
      ELP), and CM dispersion obtained by a density-gradient ultracentrifugation.
      Levels of the association of probucol with CM were largely governed by solubility
      of probucol in pharmaceutical excipients tested in this study, and the ability of
      solubilizers tested to enhance the affinity of probucol with CM was much greater
      than that of surfactants tested. Furthermore, the association of probucol with CM
      was enhanced by increasing the amount of the drug solubilized in propylene glycol
      or Transcutol HP. Together, the result of this CM-binding study showed that
      solubilizers tested in this study can increase levels of the association of
      probucol with CM, potentially leading to an increase in lymphatic exposure of
      drugs. Thus, identifying pharmaceutical excipients having better solubilizing
      ability would be advantageous for enhanced lymphatic delivery. 

PMID- 24934665
TI  - Biomimetic block copolymer particles with gated nanopores and ultrahigh protein
      sorption capacity.
AB  - The design of micro- or nanoparticles that can encapsulate sensitive molecules
      such as drugs, hormones, proteins or peptides is of increasing importance for
      applications in biotechnology and medicine. Examples are micelles, liposomes and
      vesicles. The tiny and, in most cases, hollow spheres are used as vehicles for
      transport and controlled administration of pharmaceutical drugs or nutrients.
      Here we report a simple strategy to fabricate microspheres by block copolymer
      self-assembly. The microsphere particles have monodispersed nanopores that can
      act as pH-responsive gates. They contain a highly porous internal structure,
      which is analogous to the Schwarz P structure. The internal porosity of the
      particles contributes to their high sorption capacity and sustained release
      behaviour. We successfully separated similarly sized proteins using these
      particles. The ease of particle fabrication by macrophase separation and self
      assembly, and the robustness of the particles makes them ideal for sorption,
      separation, transport and sustained delivery of pharmaceutical substances. 

PMID- 24934667
TI  - The relationship between happiness and health: evidence from Italy.
AB  - We test the relationship between happiness and self-rated health in Italy. The
      analysis relies on a unique dataset collected through the administration of a
      questionnaire to a representative sample (n = 817) of the population of the
      Italian Province of Trento in March 2011. Based on probit regressions and
      instrumental variables estimates, we find that happiness is strongly correlated
      with perceived good health, after controlling for a number of relevant socio
      economic phenomena. Health inequalities based on income, work status and
      education are relatively contained with respect to the rest of Italy. As
      expected, this scales down the role of social relationships. 

PMID- 24934668
TI  - Including the interactive effect of elevated CO2 concentration and leaf
      temperature in global models of isoprene emission.

PMID- 24934669
TI  - Multimodal imaging of aortoiliac occlusive disease with three-dimensional
      postprocessing of PET angiography and CT.
AB  - Two patients with aortoiliac occlusive disease underwent dynamic and late-static
      positron emission tomography/computed tomography (PET/CT) acquisitions with 257
      and 244 MBq F-18 FDG (CT scan parameters 50 mAs, 120 kV, pitch 1.25). Three
      dimensional reconstructions revealed an occluded aortic stent and a high-grade
      aortic stenosis and demonstrated the relations of vascular pathologies to
      adjacent structures. Early-dynamic PET can be performed without additional
      radioactive tracer and may be valuable for evaluation and intervention planning
      in patients with contraindications to other angiographic modalities. 

PMID- 24934670
TI  - Predictors of mesorectal fascia invasion after gadolinium injection in rectal
      carcinoma after neoadjuvant therapy.
AB  - OBJECTIVE: To assess spectral presaturation inversion-recovery MRI sequence with
      gadolinium to identify predictors of mesorectal fascia (MRF) invasion in patients
      with locally advanced rectal carcinoma after neoadjuvant therapy. MATERIALS AND
      METHODS: Sixty-five patients underwent neoadjuvant concomitant radiation and
      chemotherapy and surgery. Magnetic resonance images were assessed by two
      radiologists. RESULTS: Linear (odds ratio, 95% confidence intervals: 19.33, 1.98
      188.6) and reticular strands (odds ratio, 95% confidence intervals: 9.75, 1.45
      67.77) reaching the MRF are predictors of MRF invasion. CONCLUSION: Linear or
      reticular mesorectal strands reaching the MRF detected at contrast-enhanced MRI
      represent a predictor of MRF invasion.

PMID- 24934666
TI  - Platelets, a reliable source for peripheral Alzheimer's disease biomarkers?
AB  - Peripheral biomarkers play an indispensable role in quick and reliable diagnoses
      of any kind of disease. With the population ageing, the number of people
      suffering from age-related diseases is expected to rise dramatically over the
      coming decades. In particular, all types of cognitive deficits, such as
      Alzheimer's disease, will increase. Alzheimer's disease is characterised mainly
      by coexistence of amyloid plaques and neurofibrillary tangles in brain. Reliable
      identification of such molecular characteristics antemortem, however, is
      problematic due to restricted availability of appropriate sample material and
      definitive diagnosis is only possible postmortem. Currently, the best molecular
      biomarkers available for antemortem diagnosis originate from cerebrospinal fluid.
      Though, this is not convenient for routine diagnosis because of the required
      invasive lumbar puncture. As a consequence, there is a growing demand for
      additional peripheral biomarkers in a more readily accessible sample material.
      Blood platelets, due to shared biochemical properties with neurons, can
      constitute an attractive alternative as discussed here. This review summarises
      potential platelet Alzheimer's disease biomarkers, their role, implication, and
      alteration in the disease. For easy comparison of their performance, the Hedge
      effect size was calculated whenever data were available. 

PMID- 24934671
TI  - Volatile compounds of Viola odorata absolutes: identification of odorant active
      markers to distinguish plants originating from France and Egypt.
AB  - Absolutes isolated from Viola odorata leaves, valuable materials for the flavor
      and fragrance industry, were studied. Violets are mainly cultivated in France and
      Egypt and extracted locally. The absolutes of the two origins showed different
      olfactory profiles both in top and heart notes, as evidenced by sensory analysis.
      The aims of this study were i) to characterize the volatile compounds, ii) to
      determine the odorant-active ones, and iii) to identify some markers of the plant
      origin. Two complementary analytical methods were used for these purposes, i.e.,
      headspace solid-phase microextraction (HS-SPME) using different fiber coatings
      followed by GC/MS analysis and gas chromatography - olfactometry/mass
      spectrometry (GC-O/MS) applied to violet leaf extracts. From a total of 70
      identified compounds, 61 have never been reported so far for this species, 17
      compounds were characterized by both techniques (with seven among them known from
      the literature), 23 compounds were solely identified by HS-SPME GC/MS (among them
      only two being already mentioned as components of violet absolutes in the
      literature), and, finally, 30 compounds were only identified by GC-O/MS.
      According to the HS-SPME GC/MS analyses, ethyl hexanoate and (2E,6Z)-nona-2,6
      dienol were specific volatile compounds of the sample with French origin, while
      (E,E)-hepta-2,4-dienal, hexanoic acid, limonene, tridecane, and eugenol were
      specific of the samples with Egyptian origin. Additional compounds that were not
      detected by HS-SPME GC/MS analysis were revealed by GC-O analyses, some of them
      being markers of origin. Pent-1-en-3-ol, 3-methylbut-2-enal, 2-methoxy-3-(1
      methylethyl)pyrazine, 4-ethylbenzaldehyde, beta-phenethyl formate, and 2-methoxy
      3-(2-methylpropyl)pyrazine revealed to be odorant markers of the French sample,
      whereas cis-rose oxide, trans-rose oxide, and 3,5,5-trimethylcyclohex-2-enone
      were odorant markers of the Egyptian samples. 

PMID- 24934672
TI  - Binding pockets and permeation channels for dioxygen through cofactorless 3
      hydroxy-2-methylquinolin-4-one 2,4-dioxygenase in association with its natural
      substrate, 3-hydroxy-2-methylquinolin-4(1H)-one. A perspective from molecular
      dynamics simulations.
AB  - This work describes an investigation of pathways and binging pockets (BPs) for
      dioxygen (O2 ) through the cofactorless oxygenase 3-hydroxy-2-methylquinolin-4
      one 2,4-dioxygenase in complex with its natural substrate, 3-hydroxy-2
      methylquinolin-4(1H)-one, in aqueous solution. The investigation tool was random
      acceleration molecular dynamics (RAMD), whereby a tiny, randomly oriented
      external force is applied to O2 in order to accelerate its movements. In doing
      that, care was taken that the external force only continues, if O2 moves along a
      direction for a given period of time, otherwise the force changed direction
      randomly. Gates for expulsion of O2 from the protein, which can also be taken as
      gates for O2 uptake, were found throughout almost the whole external surface of
      the protein, alongside a variety of BPs for O2 . The most exploited gates and BPs
      were not found to correspond to the single gate and BP proposed previously from
      the examination of the static model from X-ray diffraction analysis of this
      system. Therefore, experimental investigations of this system that go beyond the
      static model are urgently needed. 

PMID- 24934673
TI  - Diarylheptanoids from green alder bark and their potential for DNA protection.
AB  - Nine diarylheptanoids, 1-9, catechin (11), and a phenolic glucoside, 10, were
      isolated from the bark of green alder (Alnus viridis). Four of the isolated
      compounds, i.e., 2, 5, 8, 10, are new. The structures of 1-11 were determined on
      the basis of spectroscopic data. All isolated compounds were evaluated for their
      in vitro protective effects on chromosome aberrations in peripheral human
      lymphocytes using cytokinesis-block micronucleus (CBMN) assay. Almost all of them
      exerted a pronounced effect of decreasing DNA damage of human lymphocytes, acting
      stronger than the known synthetic protector amifostine. 

PMID- 24934674
TI  - Semisynthesis and antifungal activity of novel oxime ester derivatives of
      carabrone modified at C(4) against Botrytis cinerea.
AB  - To continuously improve the potential utility of the natural lead compound of
      carabrone in agrochemistry, carabrone oxime and 36 novel oxime ester derivatives
      of carabrone modified at C(4) were synthesized, and evaluated for their
      antifungal activities against Botrytis cinerea in vitro and in vivo. Of these 36
      oxime ester derivatives, some compounds exhibited antifungal activities in vitro
      or in vivo. It was found that compounds with a pyridinyl residue can either
      efficiently inhibit spore germination or efficiently inhibit hyphal growth of B.
      cinerea, and compound 9 exhibited the highest activity in vitro and in vivo with
      IC50 and EC50 values of 1.17 and 12.9 MUg/ml, respectively. Further, the
      structure-activity relationships are also discussed.

PMID- 24934675
TI  - Chloranthones A - D: minor and unprecedented dinor-eudesmenes from Chloranthus
      elatior.
AB  - Four novel naturally occurring diastereoisomers of dinor-eudesmenes, named
      chloranthones A-D (1-4, resp.), were isolated as minor components from the EtOH
      extract of the aerial parts of Chloranthus elatior. The unprecedented framework
      was established using extensive 2D-NMR techniques. Their absolute configurations
      were deduced from the observed Cotton effects in their circular dichroism (CD)
      spectra. A plausible biosynthetic pathway to the dinor-eudesmenes is proposed. 

PMID- 24934676
TI  - Tenualexin, other phytoalexins and indole glucosinolates from wild cruciferous
      species.
AB  - In general, the chemodiversity of phytoalexins, elicited metabolites involved in
      plant defense mechanisms against microbial pathogens, correlates with the
      biodiversity of their sources. In this work, the phytoalexins produced by four
      wild cruciferous species (Brassica tournefortii, Crambe abyssinica (crambe),
      Diplotaxis tenuifolia (sand rocket), and Diplotaxis tenuisiliqua (wall rocket))
      were identified and quantified by HPLC with photodioarray and electrospray mass
      detectors. In addition, the production of indole glucosinolates, biosynthetic
      precursors of cruciferous phytoalexins, was evaluated. Tenualexin, (=2-(1,4
      dimethoxy-1H-indol-3-yl)acetonitrile), the first cruciferous phytoalexin
      containing two MeO substituents in the indole ring, was isolated from D.
      tenuisiliqua, synthesized, and evaluated for antifungal activity. The
      phytoalexins cyclobrassinin and spirobrassinin were detected in B. tournefortii
      and C. abyssinica, whereas rutalexin and 4-methoxybrassinin were only found in B.
      tournefortii. D. tenuifolia, and D. tenuisiliqua produced 2-(1H-indol-3
      yl)acetonitriles as phytoalexins. Because tenualexin appears to be one of the
      broad-range antifungals occurring in crucifers, it is suggested that D.
      tenuisiliqua may have disease resistance traits important to be incorporated in
      commercial breeding programs. 

PMID- 24934677
TI  - Sesquiterpenoids from Chloranthus henryi and their anti-neuroinflammatory
      activities.
AB  - Five new and seven known mono-sesquiterpenoids (1-5 and 6-12, resp.) together
      with five known lindenane-type disesquiterpenoids, 13-17, were isolated from the
      whole plant of Chloranthus henryi. Based on spectroscopic methods, the new
      structures were established to be (5S,6R,8S,10R)-6-hydroxyeudesma-4(15),7(11)
      diene-12,8-olide (1), 6alpha-hydroxyeudesma-4(15),7(11),8(9)-triene-12,8-olide
      (2), 8,12-epoxy-1beta-hydroxyeudesma-4(15),7,11-trien-6-one (3), 12
      oxochloraniolide A (4), and (4alpha)-8-hydroxy-12-norcardina-6,8,10-trien-11-one
      (5), respectively. Among the isolates, compound 2, zederone epoxide (8),
      spicachlorantin G (13), chloramultilide A (14), shizukaol B (15), and
      spicachlorantin B (17) showed significant anti-neuroinflammatory effects by
      inhibiting nitric-oxide (NO) production in lipopolysaccharide (LPS)-stimulated
      murine BV-2 microglial cells with relatively low cytotoxicity. 

PMID- 24934678
TI  - Two new butenolides produced by an Actinomycete Streptomyces sp.
AB  - Two new butenolides, (4S)-4,10-dihydroxydodec-2-en-1,4-olide (1) and (4S)-4,8,10
      trihydroxy-10-methyldodec-2-en-1,4-olide (2), together with three known
      compounds, MKN-003B (3), MKN-003C (4), and cyclo(Ala-Leu) (5), were isolated from
      the culture broth of a bacterium of the genus Streptomyces derived from soil
      environment. The structures of these compounds were elucidated on the basis of
      spectroscopic analysis. The inhibitory activities of the butenolides against
      eight pathogenic fungi were evaluated. All of the butenolides showed moderate-or
      weak antifungal activities in a broth microdilution assay. 

PMID- 24934679
TI  - Essential-oil composition of the needles collected from natural populations of
      Macedonian pine (Pinus peuce Griseb.) from the Scardo-Pindic mountain system.
AB  - The needle-terpene profiles of two natural Pinus peuce populations from the
      Scardo-Pindic mountain system (Mt. Osljak and Mt. Pelister) were analyzed. Among
      the 90 detected compounds, 87 were identified. The dominant constituents were
      alpha-pinene (45.5%), germacrene D (11.1%), beta-pinene (10.8%), and camphene
      (10.3%). The following eight additional components were found to be present in
      medium-to-high amounts (0.5-10%): bornyl acetate (5.0%), beta-phellandrene
      (3.4%), beta-caryophyllene (2.9%), beta-myrcene (0.9%), germacrene D-4-ol (0.9%),
      tricyclene (0.7%), (E)-hex-2-enal (0.7%), and bicyclogermacrene (0.6%). Although
      the general needle-terpene profiles of the populations from Mt. Osljak and Mt.
      Pelister were found to be similar to those of the populations from Zeletin,
      Sjekirica, and Mokra Gora (Dinaric Alps), principle component analysis (PCA) of
      eight terpenes (alpha-pinene, beta-myrcene, alpha-terpinolene, bornyl acetate,
      alpha-terpinyl acetate, beta-caryophyllene, trans-beta-farnesene, and germacrene
      D) in 139 tree samples suggested a divergence between the two population groups,
      i.e., the samples from the Scardo-Pindic mountain system and those from the
      Dinaric Alps. Genetic analysis of the beta-pinene content demonstrated a partial
      divergence between the two geographical groups. The profiles of both population
      groups differed from those published for populations from the Balkan-Rhodope
      mountains system (literature results), which were characterized by high contents
      of bornyl acetate and citronellol (Greek populations) or delta-car-3-ene
      (Bulgarian populations). 

PMID- 24934680
TI  - Inhibitory effects of constituents of an endophytic fungus Hypoxylon investiens
      on nitric oxide and interleukin-6 production in RAW264.7 macrophages.
AB  - Three new compounds, hypoxyloamide (1), 8-methoxynaphthalene-1,7-diol (2), and
      hypoxylonol (3), together with seven compounds isolated from nature for the first
      time, investiamide (4), hypoxypropanamide (5), hypoxylonol A (6), investienol
      (7), 2-heptylfuran (8), (3S)-5-methyl-8-O-methylmellein (9), (4R)-O
      methylsclerone (10), along with 19 known compounds, 11-29, were isolated from the
      culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing
      in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis.
      The structures of the new compounds were established by spectroscopic methods,
      including UV, IR, HR-ESI-MS, and extensive 1D- and 2D-NMR techniques. Of these
      isolates, 2, 8-methoxynaphthalen-1-ol (15), and 1,8-dimethoxynaphthalene (16)
      showed nitric oxide (NO) inhibitory activity with IC50 values of 11.8+/-0.9,
      17.8+/-1.1, and 13.3+/-0.5 MUM, respectively, stronger than the positive control
      quercetin (IC50 36.8+/-1.3 MUM). Compounds 2, 15, and 16 also showed interleukin
      6 (IL-6) inhibitory activity with IC50 values of 9.2+/-1.7, 18.0+/-0.6, and 2.0+/
      0.1 MUM, stronger than the positive control quercetin (IC50 31.3+/-1.6 MUM). To
      the best of our knowledge, this is the first report on guaiane sesquiterpene
      metabolites, 3, 6, and 7, from the genus Hypoxylon. 

PMID- 24934681
TI  - Anti-adipogenic activity of the naturally occurring phenanthroindolizidine
      alkaloid antofine via direct suppression of PPARgamma expression.
AB  - Antofine (ANTF) is a phenanthroindolizidine alkaloid isolated from the root of
      Cynanchum paniculatum Kitagawa (Asclepiadaceae), which is used as an herbal
      remedy for pain and inflammation. ANTF also possesses antiviral and
      antitumorigenic activities. In this study, we investigated the role of ANTF in
      adipogenesis. Chronic ABTF administration suppressed adipocyte differentiation
      and marker expression in a dose-dependent manner. Furthermore, acute
      administration of ANTF at early stages of differentiation process inhibited lipid
      droplet formation and adipogenic gene expression. ANTF Treatment decreased
      expression of PPARgamma protein, a master transcription factor in the regulation
      of adipocyte differentiation, leading to a suppression of aP2 promoter activity.
      These results suggest that ANTF exerts potent anti-adipogenic effects via direct
      suppression of PPARgamma protein expression, with consequent downregulation of
      adipogenic gene expression. 

PMID- 24934682
TI  - Cytotoxic mannopyranosides of indole alkaloids from Zanthoxylum nitidum.
AB  - Three new mannopyranosides of indole alkaloids, methyl 7-(beta-D
      mannopyranosyloxy)-1H-indole-2-carboxylate (1), methyl 7-[(3-O-acetyl-beta-D
      mannopyranosyl)oxy]-1H-indole-2-carboxylate (2), and 2-methyl-1H-indol-7-yl beta
      D-mannopyranoside (3), were isolated from an EtOH extract of the roots of
      Zanthoxylum nitidum. Their structures were identified as new compounds on the
      basis of the spectroscopic analyses. Bioactivity evaluation revealed that these
      alkaloids possess significant cytotoxicities against all the tested tumor cell
      lines with IC50 values of less than 30 MUM. 

PMID- 24934683
TI  - Cytotoxic compounds from the leaves of Garcinia polyantha.
AB  - A new compound, named banganxanthone C (=12-(1,1-dimethylprop-2-en-1-yl)-5,10
      dihydroxy-9-methoxy-2-methyl-2-(4-methylpent-3-en-1-yl)-2H,6H-pyrano[3,2
      b]xanthen-6-one; 4), together with five known compounds, were isolated from the
      leaves of Garcinia polyantha. The structures of the compounds were elucidated on
      the basis of 1D- and 2D-NMR spectroscopy. Among the known compounds, two were
      xanthones, one was a pentacyclic triterpene, one sterol, and one benzophenone
      derivative. Isoxanthochymol (2) and 4-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-1,5,8
      trihydroxy-3-methoxy-9H-xanthen-9-one (3) exhibited significant antiproliferative
      activity against the leukemia cell line TPH-1 with IC50 inhibition values of 1.5
      and 2.8 MUg/ml, respectively. The cytotoxic activity was found to be related to
      apoptosis induction. 

PMID- 24934684
TI  - New triterpenoids from the fruiting bodies of Ganoderma lucidum and their
      bioactivities.
AB  - Phytochemical investigation of the AcOEt extract of G. Lucidum has led to the
      isolation of two new triterpenoids, 1 and 2, together with five known ones, 3-7.
      The structures of the new compounds were identified as 12beta-acetoxy-3beta,7beta
      dihydroxy-11,15,23-trioxolanost-8-en-26-oic acid butyl ester (1) and 12beta
      acetoxy-3,7,11,15,23-pentaoxolanost-8-en-26-oic acid butyl ester (2) on the basis
      of detailed spectroscopic analysis (mass spectrometry, and 1D- and 2D-NMR
      experiments). The antimicrobial activities of 1 and 2 were also evaluated. 

PMID- 24934685
TI  - [Transfusion-transmitted bacterial infection of a apheresis platelet concentrate
      with Streptococcus gallolyticus: Analysis of one case].
AB  - Bacterial infections are uncommon complications of the blood products transfusion
      but they are potentially serious. Many advances have been done over the past few
      years to guarantee the microbiological security of blood products as the donors
      selection with a medical talk, the derivation of the first 30 millilitres blood
      during the donation, the deleucocytation of blood products... But in spite of
      these advances, cases of bacterial infection always remain. The purpose of this
      study was to point out the platelet concentrate's transfusion-transmitted
      bacterial infection with Streptococcus gallolyticus and the unusual consequence
      for the donor by uncovering an asymptomatic rectal neoplastic tumor. This study
      as raised as to whether the usefulness of systematic bacterial inactivation in
      the platelets concentrates. 

PMID- 24934686
TI  - Mid-term results of endovascular treatment with the Gore TAG device for
      degenerative descending thoracic aortic aneurysms.
AB  - PURPOSE: To confirm the validity of using Gore TAG for degenerative descending
      thoracic aneurysm repair, we evaluated the mid-term clinical outcomes in our
      single-center experience. METHODS: From May 2008 to April 2011, elective thoracic
      endovascular aortic repair (TEVAR) with Gore TAG without left subclavian artery
      (LSA) coverage for a degenerative descending thoracic aneurysm was performed in
      36 consecutive cases. RESULTS: The procedural success rate was 100%, and no
      patient died within 30 days of the operation. We observed no cases of paraplegia
      or stroke. The mean follow-up was 33.2 +/- 13.0 months (the maximum follow-up was
      58.0 months). The actuarial survival rate was 100, 97.2 and 94.4% at 1, 2 and 3
      years. There was no aorta-related death at 3 years. Two (5.6%) late distal Type I
      endoleaks were observed. Freedom form aortic events rate was 97.2, 97.2, and
      97.2% at 1, 2, and 3 years respectively. In six cases with bird-beak
      configurations at the 2-year follow-up, the bird-beak length and angle had
      increased gradually. CONCLUSIONS: Elective TEVAR using the Gore TAG for
      degenerative descending thoracic aortic aneurysms without LSA coverage is
      effective and provides satisfactory early and mid-term outcomes. However, since
      the bird-beak configurations progressed, a conformable and flexible device for
      the next generation of procedures will be needed.

PMID- 24934687
TI  - Population genetic structure of an invasive forensically important insect.
AB  - The forensic utility of an insect can depend in part on its population structure.
      Although some native North American species have been characterized in this
      fashion, information is lacking for species that were introduced from elsewhere
      and that might have lower genetic diversity and less geographic differentiation.
      We surveyed Chrysomya megacephala, an Asian fly present in the continental USA
      since the 1980s. Amplified Fragment Length Polymorphism profiles were generated
      from adult insects collected across Florida and in Mobile, Alabama. Analysis of
      Molecular Variance on 151 polymorphic loci found significant but very small
      variation among samples. STRUCTURE and principal coordinate analyses produced the
      same two clusters in the population, consistent with C. megacephala in Florida
      having originated from two separate source populations. A weak negative
      correlation between genetic and geographic distances probably reflected the
      geographic arrangement of the genetic clusters. A positive relative relatedness
      coefficient for each sample indicated that flies arriving at a bait within a
      short time were likely to be close relatives, consistent with the earlier results
      for native North American carrion flies. However, genetic diversity estimated for
      the introduced Florida C. megacephala was lower than for native species or for
      published data on Malaysian C. megacephala, perhaps reflecting the genetic
      effects of being introduced to a new geographic region. Genetic assignment, a
      method that has been proposed as a way to infer corpse postmortem relocation, was
      much less successful for C. megacephala compared to the native species, possibly
      reflecting a history of admixture. 

PMID- 24934688
TI  - [How can we contribute to tuberculosis control in the workplace?].

PMID- 24934689
TI  - Systemic capillary leak syndrome associated with a rare abdominal and four-limb
      compartment syndrome: a case report.
AB  - INTRODUCTION: Systemic capillary leak syndrome is a rare and life threatening
      disease characterized by periodic episodes of hypovolemic shock due to leakage of
      plasma from the intravascular to the extravascular space. It is associated with
      hemoconcentration, hypoalbuminemia, and generalized edema. We report the case of
      a patient with idiopathic systemic capillary leak syndrome who developed an
      unexpected and potentially fatal abdominal and four-limb compartment syndrome.
      This was successfully treated with fasciotomies and medical treatment including
      terbutaline, theophylline, and corticosteroids. To the best of our knowledge this
      is the first report of this kind in the literature. CASE PRESENTATION: A
      previously healthy 54-year-old Caucasian man presented to the emergency
      department of our internal medicine ward with a medical history of aggravation of
      general health related to dizziness, weight gain, and two syncopal attacks. Due
      to a massive emission of fluids and proteins from the intravascular to the
      extracellular compartments, he developed compartment syndromes in his upper and
      lower limbs and the abdominal compartment. The abdomen and all four limbs
      required decompression by a fasciotomy of both forearms, both thighs, both lower
      legs, and the abdomen within 24 hours after admission. After 60 days of treatment
      he was dismissed from the clinic. He was able to return to his previous
      occupation and reached the same level of athletic activity as before the illness.
      CONCLUSIONS: Systemic capillary leak syndrome is a very rare disease that can
      lead to a fatal clinical outcome. It is important to be aware of the fatal
      complications that can be caused by this disease. Despite the fact that systemic
      capillary leak syndrome represents a very rare disease it is still important to
      be aware of life threatening complications, like compartment syndromes, which
      need surgical intervention. However, early diagnosis and interdisciplinary
      treatment can lead to a good clinical outcome.

PMID- 24934690
TI  - Relationship between betel quid chewing and risks of cardiovascular disease in
      older adults: a cross-sectional study in Taiwan.
AB  - BACKGROUND: The association between betel quid (BQ) chewing and oral cancer is
      well established. However, evidence regarding the relationship between BQ chewing
      and cardiovascular disease (CVD) is still insufficient. METHODS: This cross
      sectional study included 2002 men and 1175 women aged 50 and older in a city
      level health examination survey of an agricultural and fishing population in
      2013. In addition to anthropometric parameters, CVD risks were estimated using
      high-sensitivity C-reactive protein (hs-CRP), brachial-ankle pulse wave velocity
      (baPWV) and ankle-brachial index. Age, gender, smoking and alcohol drinking
      status were all incorporated into the multivariate logistic regression model to
      delineate the effect of BQ chewing on CVD risks. RESULTS: Two hundred forty-one
      (12%) males and eight (0.7%) females were ever chewers. BQ chewing was an
      independent risk factor for general obesity (odds ratio [OR] 1.43, 95% confidence
      interval [CI] 1.07-1.91, p=0.017), central obesity (OR 2.27, 95% CI 1.53-3.37,
      p<0.001) and an elevated hs-CRP level (OR 1.38, 95% CI 1.03-1.85, p=0.029).
      Subjects who chewed more frequently had a higher systolic blood pressure
      (p=0.025) and baPWV (p=0.006). The waist circumference (p=0.015) and waist-to
      height ratio (p=0.022) were greater in current chewers than in former chewers.
      CONCLUSION: These findings suggest that BQ chewing is associated with obesity and
      a higher CVD risk as estimated by hs-CRP. Furthermore, potential beneficial
      effects of BQ chewing cessation on central obesity were also found.

PMID- 24934692
TI  - Biopolymers 2013: Biopolymer assemblies for material design.

PMID- 24934693
TI  - Synthesis and pharmacological evaluation of like- and unlike-configured
      tetrahydro-2-benzazepines with the alpha-substituted benzyl moiety in the 5
      position.
AB  - A large set of tetrahydro-2-benzazepines with an alpha-hydroxy or alpha
      (aryl)alkoxy substituted benzyl moiety in the 5-position was prepared according
      to the recently reported C6C1 + C3N synthetic strategy. The Heck reaction of 2
      iodobenzaldehyde acetal 4 and the subsequent Stetter reaction led to the ketone
      7, which was reduced diastereoselectively to form the like-configured alcohol 8.
      The diastereomeric unlike-configured alcohol 9 was obtained by a Mitsunobu
      inversion of 8. Alkylation and reductive cyclization of the diastereomeric
      alcohols 8 and 9 provided like- and unlike-configured 2-benzazepines 13 and 23,
      which allowed the introduction of various substituents at the N-atom. Analysis of
      the relationship between the structure and the sigma1 affinity revealed that
      large substituents such as the butyl, benzyl or 4-phenylbutyl moiety at the
      benzazepine N-atom resulted in high affinity ligands. A p-methoxybenzyl ether is
      less tolerated by the sigma1 receptor than a methyl ether or an alcohol. The
      unlike-configured alcohols 25d and 27d show slightly higher sigma1 affinity than
      their like-configured diastereomers 15d and 17d. With respect to the sigma1
      affinity, sigma1/sigma2 selectivity and lipophilic ligand efficiency, like- and
      unlike-configured alcohols 15d and 25d represent the most promising sigma1
      ligands of this series. Interactions of the novel 2-benzazepines with various
      binding sites of the NMDA receptor were not observed.

PMID- 24934691
TI  - Scientific overview: 2013 BBC plenary symposium on tobacco addiction.
AB  - Nicotine dependence plays a critical role in addiction to tobacco products, and
      thus contributes to a variety of devastating tobacco-related diseases (SGR 2014).
      Annual costs associated with smoking in the US are estimated to be between $289
      and $333 billion. Effective interventions for nicotine dependence, especially in
      smokers, are a critical barrier to the eradication of tobacco-related diseases.
      This overview highlights research presented at the Plenary Symposium of Behavior,
      Biology and Chemistry: Translational Research in Addiction Conference (BBC),
      hosted by the UT Health Science Center San Antonio, on March 9-10, 2013. The
      Plenary Symposium focused on tobacco addiction, and covered topics ranging from
      basic science to national policy. As in previous years, the meeting brought
      together globally-renowned scientists, graduate student recruits, and young
      scientists from underrepresented populations in Texas and other states with the
      goal of fostering interest in drug addiction research in young generations.

PMID- 24934695
TI  - Pathway analysis of cervical cancer genome-wide association study highlights the
      MHC region and pathways involved in response to infection.
AB  - Cervical cancer is caused by infection with human papillomavirus (HPV). A genome
      wide association study (GWAS) has identified several susceptibility loci for
      cervical cancer, but they explain only a small fraction of cervical cancer
      heritability. Other variants with weaker effect may be missed due to the
      stringent significance threshold. To identify important pathways in cervical
      carcinogenesis, we performed a two-stage pathway analysis in two independent
      GWASs in the Swedish population, using the single-nucleotide polymorphism (SNP)
      ratio test. The 565 predefined pathways from Kyoto Encyclopedia of Genes and
      Genomes and BioCarta databases were systematically evaluated in the discovery
      stage (1034 cases and 3948 controls with 632,668 SNPs) and the suggestive
      pathways were further validated in the replication stage (616 cases and 506
      controls with 341,358 SNPs). We found 12 pathways that were significant in both
      stages, and these were further validated using set-based analysis. For 10 of
      these pathways, the effect was mainly due to genetic variation within the major
      histocompatibility complex (MHC) region. In addition, we identified a set of
      novel candidate genes outside the MHC region in the pathways denoted
      'Staphylococcus aureus infection' and 'herpes simplex infection' that influenced
      susceptibility to cervical cancer (empirical P = 4.99 * 10(-5) and 4.99 * 10(-5)
      in the discovery study; empirical P = 8.98 * 10(-5) and 0.009 in the replication
      study, respectively). Staphylococcus aureus infection may evoke an inflammatory
      response that inadvertently enhances malignant progression caused by HPV
      infection, and Herpes simplex virus-2 infection may act in conjunction with HPV
      infection to increase the risk of cervical carcinoma development. These findings
      provide new insights into the etiology of cervical cancer.

PMID- 24934694
TI  - Neuropeptide precursor VGF is genetically associated with social anhedonia and
      underrepresented in the brain of major mental illness: its downregulation by
      DISC1.
AB  - In a large Scottish pedigree, disruption of the gene coding for DISC1 clearly
      segregates with major depression, schizophrenia and related mental conditions.
      Thus, study of DISC1 may provide a clue to understand the biology of major mental
      illness. A neuropeptide precursor VGF has potent antidepressant effects and has
      been reportedly associated with bipolar disorder. Here we show that DISC1
      knockdown leads to a reduction of VGF, in neurons. VGF is also downregulated in
      the cortices from sporadic cases with major mental disease. A positive
      correlation of VGF single-nucleotide polymorphisms (SNPs) with social anhedonia
      was also observed. We now propose that VGF participates in a common
      pathophysiology of major mental disease. 

PMID- 24934696
TI  - Recombinant human relaxin-2: (how) can a pregnancy hormone save lives in acute
      heart failure?
AB  - Acute heart failure (AHF) syndrome, characterized by pulmonary and/or venous
      congestion owing to increased cardiac filling pressures with or without
      diminished cardiac output, is still associated with high post-discharge mortality
      and hospitalization rates. Many novel and promising therapeutic approaches, among
      them endothelin-1, vasopressin and adenosine antagonists, calcium sensitization,
      and recombinant B-type natriuretic hormone, have failed in large studies.
      Likewise, the classic drugs, vasodilators, diuretics, and inotropes, have never
      been shown to lower mortality.The phase III trial RELAX-AHF tested recombinant
      human relaxin-2 (rhRlx) and found it to improve clinical symptoms moderately, to
      be neutral regarding the combination of death and hospitalization at day 60, to
      be safe, and to lower mortality at day 180. This review focuses on basic research
      and pre-clinical findings that may account for the benefit of rhRlx in AHF. The
      drug combines short-term hemodynamic advantages, such as moderate blood pressure
      decline and functional endothelin-1 antagonism, with a wealth of protective
      effects harboring long-term benefits, such as anti-inflammatory, anti-fibrotic,
      and anti-oxidative actions. These pleiotropic effects are exerted through a
      complex and intricate signaling cascade involving the relaxin-family peptide
      receptor-1, the glucocorticoid receptor, nitric oxide, and a cell type-dependent
      variety of kinases and transcription factors.

PMID- 24934697
TI  - Could vitamin D supplements be a new therapy for heart failure? Possible
      pathogenic mechanisms from data of intervention studies.
AB  - Vitamin D deficiency may play a role in the pathogenesis of chronic heart failure
      (HF), but whether giving patients supplements to raise vitamin D into the normal
      range improves their survival is not clear. It has been demonstrated that vitamin
      D deficiency is common in patients with HF, especially the elderly, in obese and
      in dark skinned people, and that low vitamin D levels are associated with adverse
      outcome. The epidemiological data have been confirmed by experimental data, which
      show that knockout mice for the vitamin D receptor developed myocardial
      hypertrophy and dysfunction. Data from interventional studies are scarce and
      discordant, and more research is urgently needed to confirm whether add-on
      supplementation therapy with vitamin D has a role in the management of patients
      with chronic HF.

PMID- 24934698
TI  - Risk factors and early pharmacological interventions to prevent chronic
      postsurgical pain following cardiac surgery.
AB  - Chronic postsurgical pain (CPSP) after cardiac surgery represents a significant
      clinical problem. The prevalence of CPSP varies widely between studies, but
      severe CPSP is present in less than 10% of the patients. Important differential
      diagnoses for CPSP after cardiac surgery are myocardial ischemia, sternal
      instability and mediastinitis. CPSP after cardiac surgery may be thoracic pain
      present at the site of the sternotomy or leg pain due to vein-graft harvesting.
      The CPSP can be neuropathic pain, visceral pain, somatic pain or mixed pain.
      Potential risk factors for CPSP are young age, female gender, overweight,
      psychological factors, preoperative pain, surgery-related factors and severe
      postoperative pain. In addition to standard postoperative analgesics, the use of
      N-methyl-D-aspartate (NMDA) antagonists, alpha-2 agonists, local anesthetics,
      gabapentinoids, and corticosteroids are all proposed to reduce the risk for CPSP
      after cardiac surgery. Still, no specific pharmacological therapy, cognitive
      therapy or physical therapy is established to protect against CPSP. The only
      convincing prevention of CSPS is adequate treatment of acute postoperative pain
      irrespective of method. Hence, interventions against acute pain, preferably in a
      step-wise approach titrating the interventions for each patient's individual
      needs, are essential concerning prevention of CPSP after cardiac surgery. It is
      also important that surgeons consider the risk for CPSP as a part of the basis
      for decision-making around performing a surgical procedure and that patients are
      informed of this risk.

PMID- 24934699
TI  - Screening for hepatocellular carcinoma in chronic liver disease: a systematic
      review.
AB  - BACKGROUND: Guidelines recommend routine screening for hepatocellular carcinoma
      (HCC) in high-risk patients, but the strength of evidence supporting these
      recommendations is unclear. PURPOSE: To review the benefits and harms of HCC
      screening in patients with chronic liver disease. DATA SOURCES: MEDLINE,
      PsycINFO, and ClinicalTrials.gov from inception to April 2014; Cochrane databases
      to June 2013; reference lists; and technical advisors. STUDY SELECTION: English
      language trials and observational studies comparing screening versus no
      screening, studies of harms, and trials comparing different screening intervals.
      DATA EXTRACTION: Mortality and adverse events were the outcomes of interest.
      Individual-study quality and the overall strength of evidence were dual-reviewed
      using published criteria. DATA SYNTHESIS: Of 13,801 citations, 22 studies met
      inclusion criteria. The overall strength of evidence on the effects of screening
      was very low. One large trial of patients with hepatitis B found decreased HCC
      mortality with periodic ultrasonographic screening (rate ratio, 0.63 [95% CI,
      0.41 to 0.98]), but the study was limited by methodological flaws. Another trial
      in patients with hepatitis B found no survival benefit with periodic alpha
      fetoprotein screening. In 18 observational studies, screened patients had earlier
      stage HCC than clinically diagnosed patients, but lead- and length-time biases
      confounded the effects on mortality. Two trials found no survival differences
      between shorter (3- to 4-month) and longer (6- to 12-month) screening intervals.
      Harms of screening were not well-studied. LIMITATIONS: Only English-language
      studies were included. The evidence base is limited by methodological issues and
      a paucity of trials. CONCLUSION: There is very-low-strength evidence about the
      effects of HCC screening on mortality in patients with chronic liver disease.
      Screening tests can identify early-stage HCC, but whether systematic screening
      leads to a survival advantage over clinical diagnosis is uncertain. PRIMARY
      FUNDING SOURCE: U.S. Department of Veterans Affairs Quality Enhancement Research
      Initiative.

PMID- 24934700
TI  - Overdose with modified-release paracetamol (Panadol Osteo(r)) presenting to a
      metropolitan emergency medicine network: a case series.
AB  - BACKGROUND: There are currently no large cases series documenting poisoning with
      paracetamol modified-release (Panadol Osteo(r), GlaxoSmithKline, Sydney, NSW,
      Australia). Management guidelines recommend at least two serum paracetamol
      concentrations 4 h apart and initiating treatment with N-acetylcysteine (NAC) if
      more than 10 g is ingested. OBJECTIVE: To describe a cohort of Panadol Osteo(r)
      poisoning and determine if the management of identified cases was consistent with
      existing guidelines. METHOD: Descriptive retrospective case series presenting to
      a metropolitan hospital network with paracetamol poisoning from October 2009 to
      September 2013. RESULTS: There were 42 cases of Panadol Osteo(r) poisoning
      identified. Twenty-nine patients (median ingested dose 19 950 mg) were treated
      with NAC, of which 27 were acute single ingestions. Of NAC-treated patients, 85%
      (23/27) had an initial serum paracetamol concentration that was above the
      nomogram line. However, 15% (4/27) had an initial non-toxic concentration that
      later increased above the line. In 14 untreated patients (median ingested dose
      7980 mg), one was an unrecognised late line-crosser with initial non-toxic serum
      paracetamol concentration. Only 43% (6/14) had a repeat paracetamol concentration
      measured. Three patients had a 4 h paracetamol >500 MUmol/L. Late line-crossing
      was seen in the NAC-treated group at this level. In two untreated patients, NAC
      should have been commenced on the reported dose. CONCLUSION: Most patients
      presenting with Panadol Osteo(r) poisoning requiring NAC treatment had an initial
      serum paracetamol concentration indicating need for treatment. A small number of
      late treatment nomogram line-crossers was seen on repeat paracetamol estimation.
      The current guideline for Panadol Osteo(r) poisoning would have detected all
      cases requiring NAC treatment.

PMID- 24934701
TI  - Intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the
      ventral tegmental area of prenatally stressed rats.
AB  - Exposure to a variety of stressful events during the last week of pregnancy in
      rats interferes with the correct progeny development, which in turn leads to
      delays in motor development, impaired adaptation to stressful conditions, altered
      sexual behaviour, learning deficits, neuronal development and brain morphology.
      Many of these alterations have been attributed to changes in dopamine (DA)
      neurotransmission and occur primarily in the mesolimbic system. We found that
      prenatally stressed offspring showed higher levels of cells expressing tyrosine
      hydroxylase (TH) in the ventral tegmental area (VTA) and that these cells were
      more susceptible to a neurochemical insult with 6-hydroxy-DA (6-OHDA) in
      adulthood. Moreover, prenatally stressed rats presented differences in terms of
      the number and asymmetry of neuronal nitric oxide synthase-expressing cells in
      the VTA and nucleus accumbens, respectively. Similar to the results described for
      TH-expressing cells, the nitrergic systems were differentially regulated after 6
      OHDA lesion in control and prenatally stressed rats. These results indicated that
      prenatal stress affects the dopaminergic and nitrergic systems in the mesolimbic
      pathway. In addition, we propose that the mesolimbic areas are more susceptible
      than the motor areas to a neurochemical insult during adult life. 

PMID- 24934702
TI  - Molecular and ultrastructural characterization of Dictyocoela diporeiae n. sp.
      (Microsporidia), a parasite of Diporeia spp. (Amphipoda, Gammaridea).
AB  - Dictyocoela diporeiae n. sp. is described from Diporeia spp. (Amphipoda,
      Gammaridea) collected from Lake Superior (USA), and its morphology and taxonomic
      affiliation are discussed. In hematoxylin- and eosin-stained sections of infected
      amphipods, the microsporidian was observed to infect muscle tissue surrounding
      the ovaries. Melanized hemocytic encapsulations were often observed in or near
      masses of microsporidians. The microsporidians appeared as spores measuring 1.99
      +/- 0.09 MUm long by 1.19 +/- 0.05 MUm wide. Each spore contained eight coils of
      isofilar polar filaments that were arranged in single ranks. Polar filaments
      measured 71 +/- 3 nm in diameter. A prominent lamellar polaroplast composed of
      ordered concentric membranes was found at the apical end of the spore surrounding
      the polar filament. A distinct posterior vacuole was observed at the distal end
      of the spore. Phylogenetic analysis based on 16s RNA sequences showed that the
      microsporidian belongs to the genus Dictyocoela, and is most similar to D.
      berillonum, yet distinctly different. The species is new, based on its
      morphology, genetic sequence, host, and location within the host.

PMID- 24934703
TI  - Hyperinsulinemic hypoglycemia syndrome in 2 dogs with bartonellosis.

PMID- 24934704
TI  - Factors associated with utilization of reproductive healthcare services among
      migrant women workers in Chong Qing, China.
AB  - OBJECTIVE: To investigate the use of reproductive healthcare services among
      migrant women workers in Chong Qing, China, and provide suggestions to improve
      the utilization of these services by young women. METHODS: In a qualitative
      interview-based study between March, 2013 and June, 2013, personal in-depth
      interviews were conducted among young women workers, factory doctors, healthcare
      service providers, and policy-makers in Chong Qing, China. RESULTS: Women workers
      seldom visited hospitals and did so only when their pain became unbearable. The
      workers' use of reproductive healthcare services was particularly influenced by
      the high cost of hospitalization and long waiting periods. Factory doctors could
      only solve minor problems. Public healthcare providers stated that migrant women
      had a higher morbidity rate from reproductive tract infections as compared with
      local women. The policy-makers considered that the health system was beneficial
      to women's reproductive health; however, few workers had good comprehension of
      government policies. CONCLUSION: Migrant women workers are vulnerable owing to
      lack of reproductive health care. The government and both social and health
      enterprise should consider the convenience of these women and the affordability
      of treatments when formulating reproductive healthcare policies. Effective
      measures should be taken to improve the use of these services by migrant women
      workers.

PMID- 24934705
TI  - Ultrasound diagnosis of fetal head engagement.
AB  - OBJECTIVE: To compare clinical data and transperineal ultrasound results for the
      diagnosis of fetal head engagement. METHODS: The present prospective longitudinal
      study enrolled 100 term women attending the Mongi Slim Hospital, La Marsa,
      Tunisia, between July and September 2012. The clinical assessment of fetal
      engagement was compared with ultrasound measurements. Ultrasound examination was
      performed in the delivery room. The probe was placed on the ano-vulvar area. The
      measure used was the distance between the perineum and external table of fetal
      skull. RESULTS: The ultrasound measures of the perineum to external table of
      fetal skull ranged from 13 to 75mm. The measures of the perineum to succedaneum
      bump ranged from 22 to 68mm. A threshold of 55mm was determined as the perineum
      to fetal head distance above which a diagnosis of engagement would be reversed.
      This proposed threshold had a positive predictive value of 98.6%, a sensitivity
      of 86.7%, and a specificity of 94.1%. CONCLUSION: Transperineal ultrasound is a
      simple, rapid, and reproducible method for the diagnosis of fetal head
      engagement. It can be used in the delivery room in addition to clinical
      examination and when the latter is hampered by a succedaneum bump.

PMID- 24934706
TI  - Use of a vial equilibration technique to measure the change in fugacity capacity
      of avian food and feces samples for 1,2,3,4-tetrachlorobenzene.
AB  - A vial equilibration technique was used to estimate the fugacity capacities of
      food and feces samples for 1,2,3,4-tetrachlorobenzene (TCB). The method was
      calibrated using different volumes of n-octanol and by comparing the measured and
      predicted fugacity capacity (Zoct) of n-octanol for TCB. The vial equilibration
      technique showed linearity with increasing amounts of n-octanol added to the
      vial. However, the measured Zoct was on average 8.5 times lower than the
      literature estimate and interpreted to be influenced by co-solvent effects. The
      ratio of fugacity capacities of food/feces was 2.9 and was consistent with the
      ratio estimated using Zt calculation methods (4.3) which considers partitioning
      capacity of both lipids and non-lipid organic matter. These results provide
      experimental support to the use of lipid equivalent approaches as opposed to
      lipid normalization when estimating the partition capacity of biological samples
      containing low lipid contents. 

PMID- 24934707
TI  - The swan mussel (Anodonta cygnea) in Anzali wetland of Iran, a potential
      biomonitor for Cd and Pb.
AB  - Protecting wetlands from environmental pollution has been of significant
      importance, as they are the vital habitats for various kinds of birds and
      animals. This study has aimed to monitor the contamination of Cd and Pb in Anzali
      wetland, located in the north of Iran using a mussel biomonitor. The contents of
      Cd and Pb were measured in the surface sediment, the soft tissue, and the shell
      of A. cygnea. The samples were collected from four sites in the region. The
      results demonstrated that the shell of A. cygnea can be employed as a precise
      case for biomonitoring of Cd and Pb, due to the higher biota-sediment
      accumulation factor and the lower coefficient of variation values found in the
      shell compared with the soft tissue, and also according to the positive
      correlation between Cd and Pb levels in the shell of A. cygnea and the sediment. 

PMID- 24934713
TI  - Preparation of therapeutic dose of 177Lu-DOTA-TATE using a novel single vial
      freeze-dried kit: a comparison with 'in-situ' preparation at hospital
      radiopharmacy.
AB  - OBJECTIVE: Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic
      treatment to the patients suffering from cancers of neuroendocrine origin, could
      be prepared at the hospital radiopharmacy either 'in-situ' or by using
      freezedried kits. The objective of the present work is to formulate and evaluate
      a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4
      GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies
      presently used for the preparation of the agent. EXPERIMENTAL: Freeze-dried DOTA
      TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and
      ammonium acetate, were prepared and used for the formulation of patient doses of
      (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation
      and the shelf-life of the kits was determined. The pharmacokinetic behavior of
      the agent was studied in normal Wistar rats. These kits were utilized for
      treating the patients suffering from various types of neuroendocrine cancers.
      RESULTS: The freeze-dried kits were used for the preparation of up to 7.4 GBq
      (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of
      >99% and were found to have sufficiently long shelf-life. Biological studies
      carried out in normal Wistar rats exhibited no significant accumulation of
      activity in any of the vital organs/tissue except in kidneys and non-accumulated
      activity showed major renal clearance. Clinical studies carried out in cancer
      patients exhibited accumulation of activity in the cancerous lesions and
      metastatic sites. CONCLUSION: The kit was useful for the convenient preparation
      of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The
      use of kit is expected to reduce the batch failure and radiation exposure to the
      working personnel.

PMID- 24934714
TI  - Bovine viral diarrhoea virus ('pestivirus') in Australia: to control or not to
      control?
AB  - BACKGROUND: Acute infection with bovine viral diarrhoea virus (BVDV) usually
      causes only mild clinical disease in cattle, but infection of animals of breeding
      age can result in immune suppression (resulting in an increased incidence and
      severity of secondary disease) and decreased reproductive performance. If
      infection occurs during pregnancy, the virus may cross the placenta and either
      cause abortion, establish immunotolerance and persistent infection (PI) in the
      fetus or cause congenital deformities. These outcomes depend on the stage of
      pregnancy at the time of infection. INTERNATIONAL PERSPECTIVE: BVDV is recognised
      as a disease of significant financial impact in a number of countries. As a
      result, national and regional BVDV control programs are now in place in several
      regions around the world. In Europe, these programs largely rely on the
      identification and removal of the PI animals, whereas vaccination has tended to
      be the chosen method of control in the United States. BVD IN AUSTRALIA: BVDV is
      endemic in Australian cattle populations, with more than 80% of herds surveyed
      showing some level of exposure to the pathogen. The cost to the national industry
      is estimated to be AUD57.9 million annually. This review identifies and discusses
      the challenges to BVDV control in Australia, including farmer attitudes, herd
      size, sheep as a potential reservoir host and diagnostic capabilities. We
      conclude that systematic BVDV control in Australia is, or soon will be, an
      option; however, detailed cost-benefit analyses will need to be undertaken.

PMID- 24934716
TI  - Prevalence and characteristics of systolic blood pressure thresholds in
      individuals 60 years or older.

PMID- 24934717
TI  - Occupational stress, survivorship issues and key themes in this issue:
      occupational stress, survivorship interventions, cancer in Chinese populations.

PMID- 24934718
TI  - pH-induced motion control of self-propelled oil droplets using a hydrolyzable
      gemini cationic surfactant.
AB  - Self-propelled motion of micrometer-sized substances has drawn much attention as
      an autonomous transportation system. One candidate vehicle is a chemically driven
      micrometer-sized oil droplet. However, to the best of our knowledge, there has
      been no report of a chemical reaction system controlling the three-dimensional
      motion of oil droplets underwater. In this study, we developed a molecular system
      that controlled the self-propelled motion of 4-heptyloxybenzaldehyde oil droplets
      by using novel gemini cationic surfactants containing carbonate linkages (2G12C).
      We found that, in emulsions containing sodium hydroxide, the motion time of the
      self-propelled oil droplets was longer in the presence of 2G12C than in the
      presence of gemini cationic surfactants without carbonate linkages. Moreover, in
      2G12C solution, oil droplets at rest underwent unidirectional, self-propelled
      motion in a gradient field toward a higher concentration of sodium hydroxide.
      Even though they stopped within several seconds, they restarted in the same
      direction. 2G12C was gradually hydrolyzed under basic conditions to produce a
      pair of the corresponding monomeric surfactants, which exhibit different
      interfacial properties from 2G12C. The prolonged and restart motion of the oil
      droplets were explained by the increase in the heterogeneity of the interfacial
      tension of the oil droplets. 

PMID- 24934715
TI  - Deletion of atbf1/zfhx3 in mouse prostate causes neoplastic lesions, likely by
      attenuation of membrane and secretory proteins and multiple signaling pathways.
AB  - The ATBF1/ZFHX3 gene at 16q22 is the second most frequently mutated gene in human
      prostate cancer and has reduced expression or mislocalization in several types of
      human tumors. Nonetheless, the hypothesis that ATBF1 has a tumor suppressor
      function in prostate cancer has not been tested. In this study, we examined the
      role of ATBF1 in prostatic carcinogenesis by specifically deleting Atbf1 in mouse
      prostatic epithelial cells. We also examined the effect of Atbf1 deletion on gene
      expression and signaling pathways in mouse prostates. Histopathologic analyses
      showed that Atbf1 deficiency caused hyperplasia and mouse prostatic
      intraepithelial neoplasia (mPIN) primarily in the dorsal prostate but also in
      other lobes. Hemizygous deletion of Atbf1 also increased the development of
      hyperplasia and mPIN, indicating a haploinsufficiency of Atbf1. The mPIN lesions
      expressed luminal cell markers and harbored molecular changes similar to those in
      human PIN and prostate cancer, including weaker expression of basal cell marker
      cytokeratin 5 (Ck5), cell adhesion protein E-cadherin, and the smooth muscle
      layer marker Sma; elevated expression of the oncoproteins phospho-Erk1/2, phospho
      Akt and Muc1; and aberrant protein glycosylation. Gene expression profiling
      revealed a large number of genes that were dysregulated by Atbf1 deletion,
      particularly those that encode for secretory and cell membrane proteins. The four
      signaling networks that were most affected by Atbf1 deletion included those
      centered on Erk1/2 and IGF1, Akt and FSH, NF-kappaB and progesterone and beta
      estradiol. These findings provide in vivo evidence that ATBF1 is a tumor
      suppressor in the prostate, suggest that loss of Atbf1 contributes to
      tumorigenesis by dysregulating membrane and secretory proteins and multiple
      signaling pathways, and provide a new animal model for prostate cancer. 

PMID- 24934719
TI  - Somatosensory change and pain relief induced by repetitive transcranial magnetic
      stimulation in patients with central poststroke pain.
AB  - OBJECTIVE: To quantify changes in pain and somatosensory function in patients
      with central poststroke pain (CPSP) syndrome following five sessions of
      repetitive transcranial magnetic stimulation (rTMS). METHODS: Fourteen CPSP
      patients underwent MRI-guided TMS mapping to identify the motor hotspot for
      evoked responses from a muscle corresponding to a painful region (hand, N = 11,
      or distal leg, N = 3). Targeted rTMS consisting of 2000 stimuli/10 Hz each
      session was delivered over five sessions. Quantitative somatosensory testing
      (QST) was performed within the painful area and at the contralateral mirror-image
      site at baseline and after the rTMS. RESULTS: At baseline there were significant
      sensory deficits of the affected body side for warm and cold detection and
      heat/cold pain thresholds. Following rTMS, sensory thresholds showed significant
      improvements for cold detection threshold (repeated-measures ANOVA, p = 0.04).
      Subjects' pain reports (numerical rating scale 0-10) showed modest but
      significant improvements in the first week after rTMS (baseline 7.0 +/- 1.5; post
      TMS 6.3 +/- 1.5; Wilcoxon signed-rank test, p = 0.018), and these were largely
      maintained for up to four weeks post-rTMS. Improvements in warm detection
      threshold showed a significant correlation with decrease in pain score
      (Spearman's rank-order correlation, p = 0.007). CONCLUSIONS: Five sessions of
      open-label rTMS provided analgesia and improved thermal sensibility. The
      correlation of reduction of detection threshold for warmth and pain relief
      suggest that the effect of rTMS may be mediated via circuitries that share the
      processing of noxious and thermal signals, such as the insula and the
      somatosensory and anterior cingulate cortices. QST may have a role in the
      assessment of patients with neuropathic pain for suitability for rTMS treatment
      and is likely to add to our understanding of how rTMS induces pain relief.

PMID- 24934720
TI  - The effect of dephasing on the thermoelectric efficiency of molecular junctions.
AB  - In this work we report the results of theoretical analysis of the effect of the
      thermal environment on the thermoelectric efficiency of molecular junctions. The
      environment is represented by two thermal phonon baths associated with the
      electrodes, which are kept at different temperatures. The analysis is carried out
      using the Buttiker model within the scattering matrix formalism to compute
      electron transmission through the system. This approach is further developed so
      that the dephasing parameters are expressed in terms of relevant energies,
      including the thermal energy, strengths of coupling between the molecular bridge
      and the electrodes and characteristic energies of electron-phonon interactions.
      It is shown that the latter significantly affect thermoelectric efficiency by
      destroying the coherency of electron transport through the considered system. 

PMID- 24934721
TI  - Comparison of objective muscle strength in C5-C6 and C5-C7 brachial plexus injury
      patients after double nerve transfer.
AB  - PURPOSE: The purpose of this study was to evaluate the quantitative muscle
      strength to distinguish the outcomes of different injury levels in upper arm type
      brachial plexus injury (BPI) patients with double nerve transfer. METHODS: Nine
      patients with C5-C6 lesions (age = 32.2 +/- 13.9 year old) and nine patients with
      C5-C7 lesions (age = 32.4 +/- 7.9 year old) received neurotization of the spinal
      accessory nerve to the suprascapular nerve combined with the Oberlin procedure
      (fascicles of ulnar nerve transfer to the musculocutaneous nerve) were recruited.
      The average time interval between operation and evaluation were 27.3 +/- 21.0 and
      26.9 +/- 20.6 months for C5-C6 and C5-C7, respectively. British Medical Research
      Council (BMRC) scores and the objective strength measured by a handheld
      dynamometer were evaluated in multiple muscles to compare outcomes between C5-C6
      and C5-C7 injuries. RESULTS: There were no significant differences in BMRC scores
      between the groups. C5-C6 BPI patients had greater quantitative strength in
      shoulder flexor (P = 0.02), shoulder extensor (P < 0.01), elbow flexor (P =
      0.04), elbow extensor (P = 0.04), wrist extensor (P = 0.04), and hand grip (P =
      0.04) than C5-C7 BPI patients. CONCLUSIONS: Upper arm type BPI patients have a
      good motor recovery after double nerve transfer. The different outcomes between
      C5-C6 and C5-C7 BPI patients appeared in muscles responding to hand grip, wrist
      extension, and sagittal movements in shoulder and elbow joints.

PMID- 24934722
TI  - Organization of primary health care for diabetes and hypertension in high, low
      and middle income countries.
AB  - Chronic non-communicable diseases, predominantly diabetes and cardiovascular
      disease are a major public health problem globally. The chronicity of these
      diseases necessitates a restructuring of healthcare to address the
      multidisciplinary, sustained care including psychosocial support and development
      of self-management skills. Primary healthcare with elements of the chronic-care
      model provides the best opportunity for engagement with the health system. In
      this review, the authors discuss aspects of primary healthcare for management of
      diabetes and hypertension and innovations such as mobile-phone messaging, web
      based registries, computer-based decision support systems and multifaceted health
      professionals in the care team among others that are being tested to improve the
      quality of care for these diseases in high, middle and low-income countries. The
      goal of quality care for diabetes and hypertension demands innovation within the
      realities of health systems both in high as well as low and middle-income
      countries. 

PMID- 24934723
TI  - Aberrant methylation of the MSH3 promoter and distal enhancer in esophageal
      cancer patients exposed to first-hand tobacco smoke.
AB  - PURPOSE: Polymorphisms in MSH3 gene confer risk of esophageal cancer when in
      combination with tobacco smoke exposure. The purpose of this study was to
      investigate the methylation status of MSH3 gene in esophageal cancer patients in
      order to further elucidate possible role of MSH3 in esophageal tumorigenesis.
      METHODS: We applied nested methylation-specific polymerase chain reaction to
      investigate the methylation status of the MSH3 promoter in tumors and matching
      adjacent normal-looking tissues of 84 esophageal cancer patients from a high-risk
      South African population. The Cancer Genome Atlas data were used to examine DNA
      methylation profiles at 17 CpG sites located in the MSH3 locus. RESULTS: Overall,
      promoter methylation was detected in 91.9 % of tumors, which was significantly
      higher compared to 76.0 % in adjacent normal-looking esophageal tissues (P =
      0.008). When samples were grouped according to different demographics (including
      age, gender and ethnicity) and smoking status of patients, methylation
      frequencies were found to be significantly higher in tumor tissues of Black
      subjects (P = 0.024), patients of 55-65 years of age (P = 0.032), males (P =
      0.037) and tobacco smokers (P = 0.015). Furthermore, methylation of the MSH3
      promoter was significantly more frequent in tumor samples from smokers compared
      to tumor samples from non-smokers [odds ratio (OR) = 31.9, P = 0.031]. The TCGA
      data confirmed significantly higher DNA methylation level at the MSH3 promoter
      region in tumors (P = 0.0024). In addition, we found evidence of an aberrantly
      methylated putative MSH3-associated distal enhancer element. CONCLUSION: Our
      results suggest that methylation of MSH3 together with exposure to tobacco smoke
      is involved in esophageal carcinogenesis. Due to the active role of the MSH3
      protein in modulating chemosensitivity of cells, methylation of MSH3 should
      further be examined in association with the outcome of esophageal cancer
      treatment using anticancer drugs.

PMID- 24934724
TI  - Outcome and toxicity profiles in the treatment of locally advanced lung cancer
      with volumetric modulated arc therapy.
AB  - PURPOSE: To report about the outcome of radiation treatment of advanced lung
      cancer patients with volumetric modulated arcs [RapidArc (RA)]. PATIENTS AND
      METHODS: Seventy-five consecutive patients (all stages IIIA and IIIB) were
      treated with RA. Among them 71 % were men; 25.4 % presented unspecified non-small
      cell lung cancer, 41.3% adenocarcinoma and 33.3 % squamous cell carcinoma. Of
      them, 54.7 % received sequential chemotherapy while 45.3% were treated with
      concomitant regimen. Dose prescription ranged from 54 to 72 Gy. Analysis included
      survival, local control (LC) and toxicity profiles. RESULTS: Median follow-up was
      21.2 months (range 6-75). One- two- and five-year actuarial LC was 91.9 +/- 3.2,
      79.5 +/- 5.7 and 67.4 +/- 9.5 %, respectively. Median survival was 19.0 +/- 1.1
      months. Actuarial survival at 1-2-5 years was 80.0 +/- 4.6, 38.5 +/- 5.9 and 15.2
      +/- 4.9 %, respectively. Acute toxicity of G2 was reported in 24, 25.3 and 4.0 %
      of patients for lung, esophageal and hematological profiles. A total of 2.7 % of
      patients reported G3 toxicity in the esophagus and 5.3 % of the patients
      experienced G3-G4 hematological toxicity. Significant differences were observed
      in all cases between concomitant and sequential chemotherapy regiments. Only 1.3
      % (1 patient) showed G2 lung late toxicity. No significant correlation was found
      between toxicity and organ's irradiation levels. CONCLUSION: RA proved to be a
      safe and advantageous treatment modality for advanced lung cancer with results in
      line with expectations from earlier literature.

PMID- 24934726
TI  - Bacteria diversity, distribution and insight into their role in S and Fe
      biogeochemical cycling during black shale weathering.
AB  - A group of black shale samples, which were collected sequentially along a
      continuous depositional unit from bottom fresh zone toward the surface regolith
      of the weathering profile at Chengkou County, Southwest China, were examined
      using mineralogical, geochemical and pyrosequencing techniques. The mineralogical
      and geochemical analyses indicated that the black shale profile provided a series
      of extremely acidic and chemical species that changed microbial habitats
      following the process of weathering. This finding is in contrast with a previous
      hypothesis that a low-diversity bacterial community existed in these harsh
      environments; the pyrosequencing analyses showed extremely diverse microbial
      communities with 33 different phyla/groups in these samples. Among these
      phyla/groups, proteobacteria, actinobacteria and firmcutes were more dominant
      than other phyla, and the phylogenetic structures of the bacterial communities
      vary with the progressive process of weathering. Moreover, the canonical
      correlation analysis suggested that pH and sulfur in sulfate, followed by total
      Fe and sulfur in pyrite, are the significant factors that shape the microbial
      community structure. In addition, a large proportion of S- and Fe-related
      bacteria, such as Acidithiobacillus, Sulfobacillus, Thiobacillus, Ferrimicrobium
      and Ferrithrix, may be responsible for pyrite bio-oxidation, as well as for S and
      Fe biogeochemical cycling, in the black shale weathering environments. 

PMID- 24934727
TI  - Spinal injury in ankylosing spondylitis.

PMID- 24934725
TI  - Comparison of cetuximab to bevacizumab as the first-line bio-chemotherapy for
      patients with metastatic colorectal cancer: superior progression-free survival is
      restricted to patients with measurable tumors and objective tumor response--a
      retrospective study.
AB  - PURPOSE: We aimed to compare the treatment efficacy of cetuximab versus
      bevacizumab in combination with either irinotecan-based or oxaliplatin-based
      regimens (targeted triplet) as the first-line treatment for patients with
      metastatic colorectal cancer. METHODS: Between April 2005 and March 2012,
      patients (n = 158) diagnosed with metastatic colorectal cancer after at least
      four courses of first-line bevacizumab-based (n = 95) or cetuximab-based triplet
      (n = 63) were retrospectively analyzed. The KRAS genotypes were sequenced for all
      patients. The Kaplan-Meier method was used for survival analysis, and Cox
      proportional hazards models were used for univariate and multivariate analyses.
      RESULTS: Cetuximab-based triplet was associated with a higher objective response
      rate (66.0 vs. 47.2 %, p = 0.037) and a higher conversion rate to resectability
      (39.7 vs. 20.0 %, p = 0.007) compared to bevacizumab-based triplet. Compared with
      bevacizumab-based triplet, cetuximab-based triplet significantly increased
      progression-free survival in patients with measurable metastatic colorectal
      cancer who achieved objective tumor response (responders) (median 13.1 vs. 10.5
      months, p = 0.023), but no significant increase was observed for overall
      survival. After adjustment for group differences in baseline characteristics and
      combined chemotherapy agents, cetuximab-based triplet remained an independent
      determinant of progression-free survival in responders as compared with
      bevacizumab-based triplet. KRAS mutation was not a prognostic factor in patients
      with metastatic colorectal cancer. CONCLUSIONS: As compared with bevacizumab
      based triplet, cetuximab-based triplet as the first-line treatment of metastatic
      colorectal cancer was associated with better progression-free survival in
      patients with measurable tumors who achieved objective tumor response to bio
      chemotherapy.

PMID- 24934728
TI  - Phenotype prediction based on genome-wide DNA methylation data.
AB  - BACKGROUND: DNA methylation (DNAm) has important regulatory roles in many
      biological processes and diseases. It is the only epigenetic mark with a clear
      mechanism of mitotic inheritance and the only one easily available on a genome
      scale. Aberrant cytosine-phosphate-guanine (CpG) methylation has been discussed
      in the context of disease aetiology, especially cancer. CpG hypermethylation of
      promoter regions is often associated with silencing of tumour suppressor genes
      and hypomethylation with activation of oncogenes.Supervised principal component
      analysis (SPCA) is a popular machine learning method. However, in a recent
      application to phenotype prediction from DNAm data SPCA was inferior to the
      specific method EVORA. RESULTS: We present Model-Selection-SPCA (MS-SPCA), an
      enhanced version of SPCA. MS-SPCA applies several models that perform well in the
      training data to the test data and selects the very best models for final
      prediction based on parameters of the test data.We have applied MS-SPCA for
      phenotype prediction from genome-wide DNAm data. CpGs used for prediction are
      selected based on the quantification of three features of their methylation
      (average methylation difference, methylation variation difference and methylation
      age-correlation). We analysed four independent case-control datasets that
      correspond to different stages of cervical cancer: (i) cases currently
      cytologically normal, but will later develop neoplastic transformations, (ii,
      iii) cases showing neoplastic transformations and (iv) cases with confirmed
      cancer. The first dataset was split into several smaller case-control datasets
      (samples either Human Papilloma Virus (HPV) positive or negative). We demonstrate
      that cytology normal HPV+ and HPV- samples contain DNAm patterns which are
      associated with later neoplastic transformations. We present evidence that DNAm
      patterns exist in cytology normal HPV- samples that (i) predispose to neoplastic
      transformations after HPV infection and (ii) predispose to HPV infection itself.
      MS-SPCA performs significantly better than EVORA. CONCLUSIONS: MS-SPCA can be
      applied to many classification problems. Additional improvements could include
      usage of more than one principal component (PC), with automatic selection of the
      optimal number of PCs. We expect that MS-SPCA will be useful for analysing recent
      larger DNAm data to predict future neoplastic transformations.

PMID- 24934729
TI  - Polysaccharide extracts of the brown alga Sargassum asperifolium possess in vitro
      cancer chemopreventive properties.
AB  - The cancer chemopreventive activity of the polysaccharide extracts (E1-E4) of
      Sargassum asperifolium, a brown alga in Red Sea shores in Egypt, was
      investigated. Tumour anti-initiation activity (the modulation of carcinogen
      metabolism) indicated that E3 and E4 were potent anti-initiators by inhibiting
      the carcinogen activator cytochrome P450-1A, and enhancing carcinogen
      detoxification enzymes glutathione-S-transferase. Only E4 significantly enhanced
      quinone reductase activity. All polysaccharide extracts possessed anti-promotion
      property by their anti-inflammatory activity. E3 and E4 dramatically induced the
      growth of spleen macrophages. E2, E3 and E4 significantly inhibited nitric oxide
      generation from lipopolysaccharide (LPS)-stimulated spleen macrophages, while E1,
      E3 and E4 led to significant inhibition of LPS-induced tumour necrosis factor
      alpha. The extracts E1, E2 and E4 showed cytotoxicity against HepG2 cells, where
      E2 and E4 induced cell death due to apoptosis. In conclusion, E3 and E4 are
      promising cancer chemopreventive extracts, since they had tumour anti-initiating
      activity via their protective modulation of carcinogen metabolism. 

PMID- 24934730
TI  - Mutational analysis of AGXT in two Chinese families with primary hyperoxaluria
      type 1.
AB  - BACKGROUND: Primary hyperoxaluria type 1 is a rare autosomal recessive disease of
      glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme
      alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent
      urolithiasis, and nephrocalcinosis. METHODS: Two unrelated patients with
      recurrent urolithiasis, along with members of their families, exhibited mutations
      in the AGXT gene by PCR direct sequencing. RESULTS: Two heterozygous mutations
      that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in
      one patient. The p.S81X mutation is novel. Two heterozygous missense mutations,
      p.M1T and p.I202N, were detected in another patient but were not identified in
      her sibling. These four mutations were confirmed to be of paternal and maternal
      origin. CONCLUSIONS: These are the first cases of primary hyperoxaluria type 1 to
      be diagnosed by clinical manifestations and AGXT gene mutations in mainland
      China. The novel p.S81X and p.I202N mutations detected in our study extend the
      spectrum of known AGXT gene mutations.

PMID- 24934731
TI  - An increased incidence of total anomalous pulmonary venous connection among
      Hispanics in southern Nevada.
AB  - OBJECTIVE: Ethnicity may influence the occurrence of specific cardiac
      malformations. DESIGN: We retrospectively analyzed the occurrence of isolated
      total anomalous pulmonary venous connection in the Hispanic and non-Hispanic
      populations of Southern Nevada over a 10-year period from 2003 to 2013. RESULTS:
      The mean cases per 100,000 live births among Hispanics was 19.8 (99% confidence
      interval 5.9-33.7) and among non-Hispanics was 2.5 (99% confidence interval 0.4
      4.6), P = 0.007. CONCLUSIONS: We found a significantly higher incidence of
      isolated total anomalous pulmonary venous connection in Hispanics vs. non
      Hispanics.

PMID- 24934733
TI  - Acute superior mesenteric venous thrombosis: transcatheter thrombolysis and
      aspiration thrombectomy therapy by combined route of superior mesenteric vein and
      artery in eight patients.
AB  - PURPOSE: To assess the feasibility, effectiveness, and safety of catheter
      directed thrombolysis and aspiration thrombectomy therapy by combined route of
      superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric
      venous thrombosis (ASMVT). METHODS: This retrospective study reviewed eight ASMVT
      patients with transcatheter direct thrombolysis and aspiration thrombectomy
      therapy via SMV and indirect thrombolysis via SMA during a period of 14 months.
      The demographics, etiology, risk factors, therapeutic effect, complications,
      mortality, and follow-up of the study population were assessed. Anatomic and
      imaging classification of location and extent of thrombus at diagnosis and degree
      of thrombus lysis were described. RESULTS: Technical success was achieved with
      substantial improvement in symptoms and thrombus resolution after thrombolytic
      therapy in all patients. The local urokinase infusion by SMA and SMV was
      performed for 5-7 (6.13 +/- 0.83) and 7-15 (12 +/- 2.51) days. Anticoagulation
      was performed catheter-directed and then orally throughout hospitalization and
      after discharge. Four patients required delayed localized bowel resection after
      thrombolytic therapy with no death. Thrombolytic therapy was not interrupted
      despite minor bleeding at the puncture site in two patients and sepsis in another
      two postoperatively. Nearly complete removal of thrombus was demonstrated by
      contrast-enhanced CT scan and portography before discharge. Patients were
      discharged in 10-27 (19.25 +/- 4.89) days after admission. No recurrence
      developed during the follow-up of 10-13 (12.13 +/- 0.99) months. CONCLUSIONS:
      Catheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial
      for ASMVT in avoiding patient death, efficient resolving thrombus, rapid
      improving symptoms, reversing extensive intestinal ischemia, averting bowel
      resection, or localizing infarcted bowel segment and preventing short bowel
      syndrome.

PMID- 24934732
TI  - A randomized, prospective, parallel group study of laparoscopic versus
      laparoendoscopic single site donor nephrectomy for kidney donation.
AB  - Few prospective, randomized studies have assessed the benefits of
      laparoendoscopic single site donor nephrectomy (LESS-DN) over laparoscopic donor
      nephrectomy (LDN). Our center initiated such a trial in January 2011, following
      subjects randomized to LESS-DN versus LDN from surgery through 5 years
      postdonation. Subjects complete recovery/satisfaction questionnaires at 2, 6 and
      12 months postdonation; transplant recipient outcomes are also recorded. One
      hundred subjects (49 LESS-DN, 51 LDN) underwent surgery; donor demographics were
      similar between groups, and included a predominance of female, living-unrelated
      donors, mean age of 47 years who underwent left donor nephrectomy. Operative
      parameters (overall time, time to extraction, warm ischemia time, blood loss)
      were similar between groups. Conversion to hand-assist laparoscopy was required
      in 3 LESS-DN (6.1%) versus 2 LDN (3.9%; p = 0.67). Questionnaires revealed that
      97.2% of LESS-DN versus 79.5% of LDN (p = 0.03) were 100% recovered by 2 months
      after donation. No significant difference was seen in satisfaction scores between
      the groups. Recipient outcomes were similar between groups. Our randomized trial
      comparing LESS donor nephrectomy to LDN confirms that LESS-DN offers a safe
      alternative to conventional LDN in terms of intra- and post-operative
      complications. LDN and LESS-DN offer similar recovery and satisfaction after
      donation. 

PMID- 24934734
TI  - Use of percutaneous aspiration thrombectomy vs. anticoagulation therapy to treat
      acute iliofemoral venous thrombosis: 1-year follow-up results of a randomised,
      clinical trial.
AB  - PURPOSE: The purpose of this study was to compare the efficacy of percutaneous
      aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with
      anticoagulation therapy alone, for the treatment of acute proximal lower
      extremity deep vein thrombosis. METHODS: In this randomised, prospective study,
      42 patients with acute proximal iliofemoral deep vein thrombosis documented via
      Doppler ultrasound examination, were separated into an interventional treatment
      group (16 males, 5 females, average age 51 years) and a medical treatment group
      (13 males, 8 females, average age 59 years). In the interventional group, PAT
      with large-lumen 9-F diameter catheterisation was applied, after initiation of
      standard anticoagulant therapy. Balloon angioplasty (n 19) and stent
      implementation (n: 14) were used to treat patients with residual stenosis (>50 %)
      after PAT. Prophylactic IVC filters were placed in two patients. The thrombus
      clearance status of the venous system was evaluated by venography. In both the
      medical and interventional groups, venous patency rates and clinical symptom
      scores were evaluated at months 1, 3, and 12 after treatment. RESULTS: Deep
      venous systems became totally cleared of thrombi in 12 patients treated with PAT.
      The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional
      and medical treatment groups, respectively. A statistically significant
      improvement was observed in clinical symptom scores of the interventional group
      (PAT) with or without stenting (4.23 +/- 0.51 before treatment; 0.81 +/- 0.92 at
      month 12) compared with the medical treatment group (4.00 +/- 0.63 before
      treatment; 2.43 +/- 0.67 at month 12). During follow-up, four patients in the
      medical treatment and one in the interventional group developed pulmonary
      embolisms. CONCLUSIONS: For treatment of acute deep vein thrombosis, PAT with or
      without stenting is superior to anticoagulant therapy alone in terms of both
      ensuring venous patency and improving clinical symptoms. PAT is a safe,
      inexpensive, and easily performed method of endovascular treatment with a low
      rate of major complications. Our present findings and literature data suggest
      that PAT can be used as first-line treatment in proximal deep vein thrombosis
      patients, especially when thrombolytic treatment is contraindicated.

PMID- 24934735
TI  - Chemoembolization of extrahepatic collateral arteries for treatment of
      hepatocellular carcinoma in the caudate lobe of the liver.
AB  - PURPOSE: This study was designed to evaluate the efficacy and safety in
      performing chemoembolization of extrahepatic collateral arteries (EHC) for
      hepatocellular carcinoma (HCC) located in the caudate lobe. METHODS: Between
      January 2006 and November 2013, chemoembolization via EHC was performed in 35
      patients with 35 caudate HCCs. Preprocedural and follow-up CT or MR scans,
      angiographic images, and medical records were reviewed retrospectively in
      consensus. Chi-square analysis was used to evaluate the relationship between
      tumor characteristics and type of EHC and that between tumor response and the
      characteristics of the tumor and chemoembolization. RESULTS: In 31 (88.6 %)
      patients, EHCs supplying the caudate HCC originated from the right inferior
      phrenic artery (RIPA). The remaining four HCCs were supplied by the
      gastroduodenal artery, dorsal pancreatic artery, and right and left gastric
      arteries. Superselective catheterization of tumor-feeding vessels from the EHC
      was achieved in 27 patients (77.1 %). There were no major complications.
      Individual tumor response supplied by the EHC at follow-up contrast-enhanced CT
      were as follows: complete response (n = 18), partial response (n = 9), stable
      disease (n = 3), and progressive disease (n = 3). Non-RIPA EHCs were
      significantly more common in patients who had previously received
      chemoembolization via the RIPA (50 %) than those who had not (6.5 %; P = 0.01).
      There was no significant predictive factor associated with tumor response.
      CONCLUSIONS: HCC in the caudate lobe can be supplied by several EHCs.
      Chemoembolization via these arteries can be performed safely and effectively.

PMID- 24934736
TI  - The accordion sign in the transplant ureter: ramifications during balloon
      dilation of strictures.
AB  - PURPOSE: This study was designed to demonstrate the accordion sign within the
      transplant ureter and evaluate its ramifications during balloon dilation of
      strictures. METHODS: A retrospective electronic chart and imaging review included
      demographic characteristics, procedure reports, and complications of 28 renal
      transplant patients having ureteral strictures treated with percutaneous balloon
      dilation reported in our transplant nephrology database during an 8-year period.
      The accordion sign was deemed present or absent on the basis of an imaging review
      and was defined as present when a tortuous ureter became kinked and irregular
      when foreshortened after placement of a wire or a catheter. Procedure-related
      urine leaks were categorized as occurring at the stricture if within 2 cm;
      otherwise, they were considered away from the stricture. RESULTS: The accordion
      sign was associated with a significantly greater occurrence of leaks away from
      the stricture (P = 0.001) but not at the stricture (P = 0.34). CONCLUSIONS: The
      accordion sign is an important consideration when performing balloon dilation
      procedures on transplant ureteral strictures, given the increased risk of leak
      away from the stricture. Its presence should prompt additional care during wire
      and catheter manipulations.

PMID- 24934738
TI  - A randomized controlled trial of hypnosis compared with biofeedback for adults
      with chronic low back pain.
AB  - BACKGROUND: Chronic low back pain (CLBP) is common and results in significant
      costs to individuals, families and society. Although some research supports the
      efficacy of hypnosis for CLBP, we know little about the minimum dose needed to
      produce meaningful benefits, the roles of home practice and hypnotizability on
      outcome, or the maintenance of treatment benefits beyond 3 months. METHODS: One
      hundred veterans with CLBP participated in a randomized, four-group design study.
      The groups were (1) an eight-session self-hypnosis training intervention without
      audio recordings for home practice; (2) an eight-session self-hypnosis training
      intervention with recordings; (3) a two-session self-hypnosis training
      intervention with recordings and brief weekly reminder telephone calls; and (4)
      an eight-session active (biofeedback) control intervention. RESULTS: Participants
      in all four groups reported significant pre- to post-treatment improvements in
      pain intensity, pain interference and sleep quality. The hypnosis groups combined
      reported significantly more pain intensity reduction than the control group.
      There was no significant difference among the three hypnosis conditions. Over
      half of the participants who received hypnosis reported clinically meaningful (>=
      30%) reductions in pain intensity, and they maintained these benefits for at
      least 6 months after treatment. Neither hypnotizability nor amount of home
      practice was associated significantly with treatment outcome. CONCLUSIONS: The
      findings indicate that two sessions of self-hypnosis training with audio
      recordings for home practice may be as effective as eight sessions of hypnosis
      treatment. If replicated in other patient samples, the findings have important
      implications for the application of hypnosis treatment for chronic pain
      management.

PMID- 24934737
TI  - Three-dimensional path planning software-assisted transjugular intrahepatic
      portosystemic shunt: a technical modification.
AB  - PURPOSE: This study was designed to report our results with a modified technique
      of three-dimensional (3D) path planning software assisted transjugular
      intrahepatic portosystemic shunt (TIPS). METHODS: 3D path planning software was
      recently developed to facilitate TIPS creation by using two carbon dioxide
      portograms acquired at least 20 degrees  apart to generate a 3D path for overlay
      needle guidance. However, one shortcoming is that puncturing along the overlay
      would be technically impossible if the angle of the liver access set and the
      angle of the 3D path are not the same. To solve this problem, a prototype 3D path
      planning software was fitted with a utility to calculate the angle of the 3D
      path. Using this, we modified the angle of the liver access set accordingly
      during the procedure in ten patients. RESULTS: Failure for technical reasons
      occurred in three patients (unsuccessful wedged hepatic venography in two cases,
      software technical failure in one case). The procedure was successful in the
      remaining seven patients, and only one needle pass was required to obtain portal
      vein access in each case. The course of puncture was comparable to the 3D path in
      all patients. No procedure-related complication occurred following the
      procedures. CONCLUSIONS: Adjusting the angle of the liver access set to match the
      angle of the 3D path determined by the software appears to be a favorable
      modification to the technique of 3D path planning software assisted TIPS.

PMID- 24934740
TI  - An efficient dye-sensitized BiOCl photocatalyst for air and water purification
      under visible light irradiation.
AB  - A photosensitized BiOCl catalyst was found to be effective for photocatalytic
      water purification and air remediation under visible light irradiation (lambda >
      420 nm). Prepared by a solvothermal method, the BiOCl crystals possessed a 3D
      hierarchical spherical structure with the highly active facets exposed. When
      sensitized by Rhodamine B (RhB), the photocatalyst system was more active than N
      doped TiO2 for breaking down 4-chlorophenol (4-CP, 200 ppm) and nitric monoxide
      (NO, 500 ppb). The high activity could be attributed to the hierarchical
      structure (supplying feasible reaction tunnels for adsorption and transition of
      reactants or products) and the efficient exposure of the {001} facets. The former
      provides an enriched oxygen atom density that promotes adsorption of cationic dye
      RhB, and creates an oxygen vacancy state. The HO and O2(-) radicals produced from
      the injected electrons from the excited dye molecule (RhB*) into the conduction
      band of BiOCl were responsible for the excellent photocatalytic performance of
      the RhB-BiOCl system.

PMID- 24934739
TI  - The risk of placental abruption and placenta previa in pregnant women with
      chronic hepatitis B viral infection: a systematic review and meta-analysis.
AB  - INTRODUCTION: Several epidemiological studies have found a positive association
      between chronic hepatitis B virus (CHB) infection and the risk of placental
      abruption and placenta previa, but various studies have reported conflicting
      findings. The objective was to systematically review the literature to determine
      a possible association between CHB infection and these two placental
      complications. METHODS: We conducted a computerized search in electronic database
      through March 1, 2014, supplemented with a manual search of reference lists, to
      identify original published research on placental abruption and placenta previa
      rates in women with CHB infection. Data were independently extracted, and
      relative risks were calculated. The meta-analysis was performed using Stata
      version 10.0 software. RESULTS: Five studies involving 9088 placenta previa cases
      were identified. No significant association between CHB infection and placenta
      previa was identified (OR = 0.98, 95% CI = 0.60-1.62). Five studies involving
      15571 placental abruption cases were identified. No significant association
      between CHB infection and placental abruption was identified (OR = 1.42, 95% CI,
      0.93-2.15). DISCUSSION: The immune response against the virus represents a key
      factor in determining infection outcomes. No observation of significant increased
      risk of the placental complications could be partially explained by the complex
      immune response during CHB infection. CONCLUSIONS: Our meta-analysis found no
      evidence of significant associations between CHB infection and increased risk of
      placental abruption as well as placenta previa. Further well-designed studies
      were warranted to assess any potential association between CHB infection and
      increased risk of placental abruption as well as placenta previa.

PMID- 24934741
TI  - 40 GHz RF biosensor based on microwave coplanar waveguide transmission line for
      cancer cells (HepG2) dielectric characterization.
AB  - This paper presents a 40-GHz RF biosensor that involves using a microwave
      coplanar waveguide (CPW) transmission line for the dielectric characterization of
      cancer cells (Hepatoma G2, HepG2). In the past, conventional resonator-based
      biosensors were designed to operate at a specific resonant peak; however, the
      dielectric sensitivity of the cells was restricted to a narrow bandwidth. To
      provide a very wide bandwidth (1-40 GHz), biosensors were based on a microwave
      CPW transmission line. The proposed biosensor can rapidly measure two frequency
      dependent cell-based dielectric parameters of HepG2 cells, microwave attenuation
      (alpha(f)cell) and the dielectric constant (epsilonr(f)cell), while removing the
      microwave parasitic effects (including the cultured medium and substrate
      materials). The proposed biosensor can be applied in postoperative cancer
      diagnosis.

PMID- 24934742
TI  - 3D graphene nano-grid as a homogeneous protein distributor for ultrasensitive
      biosensors.
AB  - In order to realize the protein uniform immobilization, a 3D nano-gird
      architecture of thiol grafted graphene film was fabricated to serve as a novel
      linker between protein and substrate. Relied on the online monitor by QCM,
      graphene deposition process can be exactly controlled to construct the perfect
      and continuous cavities with the consistent size of 500 nm. The synergetic
      characterization of FESEM and Nano-indentation characterizations have revealed
      the strong stability of grid structure to provide a firm foundation for further
      protein adsorption. Instead of common partial aggregation behavior, proteins can
      be spontaneously distributed into cavities by the interaction from thiol group.
      According to the verifications of various proteins, the efficiency of this
      distributor will not be constricted by the category and amount of protein, which
      exhibit its versatility of homogeneous distribution. Glucose and lactate oxidase
      loaded graphene distributors were directly served as biosensors to verify the
      superiority of distribution. Their sensitivities can be remarkably improved three
      times since the adoption of this nano-grid structured graphene distributor.

PMID- 24934743
TI  - Highly selective turn-on fluorescent sensor for nanomolar detection of
      biologically important Zn2+ based on isonicotinohydrazide derivative: application
      in cellular imaging.
AB  - A new Zn(2+) selective chemosensor (3) was synthesized by condensation of
      commercially available substituted salicylaldehyde and isonicotinohydrazide, and
      characterized by single crystal X-ray crystallography. Receptor 3 with Zn(2+)
      exhibited a highly selective and pronounced enhancement in the fluorescence
      emission among different cations by forming a 2:1 complex. The receptor can
      detect Zn(2+) up to nanomolar level (6.75 nM) with good tolerance of other metal
      ions and can be used for in vitro cellular imaging.

PMID- 24934744
TI  - Label-free enumeration of colorectal cancer cells from lymphocytes performed at a
      high cell-loading density by using interdigitated ring-array microelectrodes.
AB  - We report the label-free enumeration of human colorectal-carcinoma cells from
      blood lymphocytes by using interdigitated ring-array microelectrodes; this
      enumeration was based on the dielectrophoretic selection of cells. Because of the
      novel design of the device, a continuous flow of cells is uniformly distributed
      into parallel streams through 300 rings (~40 MUm in diameter each) that are
      integrated into the electrode digits. Using this array, 82% of cancer cells were
      recovered and 99% of blood lymphocytes were removed. Most of the cancer cells
      recovered were viable (94%) and could be cultivated for >8 days, during which
      period they retained their normal cell morphology and proliferation rates. The
      recovery rate correlated closely with cancer-cell loadings in spiked samples and
      this relationship was linear over a range of at least 2 orders of magnitude.
      Importantly, because of the 3D structure of the rings, these results were
      obtained at a high cell-loading concentration (10(7)cells/mL). The rings could be
      further optimized for use in accurate label-free identification and measurement
      of circulating tumor cells in cancer research and disease management.

PMID- 24934746
TI  - Recent research trends of radio-frequency biosensors for biomolecular detection.
AB  - This article reviews radio-frequency (RF) biosensors based on passive and/or
      active devices and circuits. In particular, we focus on RF biosensors designed
      for detection of various biomolecules such as biotin-streptavidin, DNA
      hybridization, IgG, and glucose. The performance of these biosensors has been
      enhanced by the introduction of various sensing schemes with diverse
      nanomaterials (e.g., carbon nanotubes, graphene oxide, magnetic and gold
      nanoparticles, etc.). In addition, the RF biosensing platforms that can be
      associated with an RF active system are discussed. Finally, the challenges of RF
      biosensors are presented and suggestions are made for their future direction and
      prospects. 

PMID- 24934745
TI  - Self-assemble ZnMn2O4 hierarchical hollow microspheres into self-supporting
      architecture for enhanced biosensing performance.
AB  - We demonstrate a facile and scalable approach to fabricate and self-assemble the
      hierarchical hollow microspheres into self-supporting architecture by naturally
      grown branches. The supporting branches can afford integrated transport channels
      and significantly improve the kinetic performance and mechanical stability.
      Meanwhile, the supported hierarchical microspheres acting as functional cell can
      provide high active sites, multiple response and suitable environment for
      immobilizing biomolecules. Different enzymes are immobilized for biosensors. The
      experiments demonstrate that the effective assembly of hierarchical microspheres
      into large size ordered architecture by self-supporting branches can
      significantly enhance the biosensing performance. 

PMID- 24934747
TI  - SERS molecular sentinel for the RNA genetic marker of PB1-F2 protein in highly
      pathogenic avian influenza (HPAI) virus.
AB  - We have developed a simple and sensitive assay for the detection of the RNA
      genetic marker associated with high pathogenicity influenza (HPAI) virus. The
      assay constituted of an array of Raman label tagged hairpin-DNA immobilized on a
      surface-enhanced Raman scattering (SERS) active substrate as the molecular
      sentinel (MS) reporter. Upon incubation of the assay with the target RNA, the
      structure of the hairpin-DNA probe changed from stem-loop configuration (closed
      state) to DNA/RNA hybridization configuration (open state) so that the Raman
      label tag will be physically separated from the SERS substrate and induce a
      decrease of Raman scattering intensity. A metal film over nanosphere (MFON)
      substrate was developed with a SERS enhancement of about 1.7 * 10(5). Based on
      this MS-modified substrate, the SERS signal showed a linear relationship to the
      target RNA in the range of 0-60 attomoles and the limit of detect is 2.67
      attomoles. The non-complementary RNA sequences control was also detected and no
      spectral response was observed. The sensing process only required a single
      hybridization step and post-hybridization washing could also be omitted. Given
      that this ultrasensitive biosensor assay is free of polymerase chain reaction
      (PCR) amplification, it would be a potential diagnostic tool for point-of-care
      HPAI virus detection.

PMID- 24934748
TI  - DNA-length-dependent fluorescent sensing based on energy transfer in self
      assembled multilayers.
AB  - In this paper, a novel DNA-length-dependent fluorescent sensor was constructed
      based on the fluorescence resonance energy transfer. In the self-assembled
      multilayers (Quartz/GO/PDDA/Tx-DNA/PDDA/ZnO@CdS), ZnO@CdS and graphene oxide(GO)
      were employed as an energy donor and an energy acceptor, respectively. Single
      stranded Tx-DNA (x represents different chain length of DNA) and
      poly(diallydimethylammonium) chloride (PDDA) were used as a linker. In the
      presence of complementary Px-DNA, the formation of double-stranded DNA leads to a
      change in chain length and achieves the purpose of changing the distance between
      ZnO@CdS and GO. Thereby, it enhances the efficiency of energy transfer between
      ZnO@CdS and GO resulting in the quench of fluorescence of ZnO@CdS, and thus
      different length DNA sequence was detected. 

PMID- 24934749
TI  - Comparative syntheses of tetracycline-imprinted polymeric silicate and acrylate
      on CdTe quantum dots as fluorescent sensors.
AB  - The amphoteric drug molecule tetracycline, which contains groups with pKa 3.4
      9.9, was used as a template for conjugating molecularly imprinted polymers (MIPs)
      and as a quencher for CdTe quantum dot (QD) fluorescence. Two MIP-QD composites
      were synthesized by a sol-gel method using a silicon-based monomer and a monomer
      linker between the MIP and QD, i.e., tetraethoxylsilane/3
      mercaptopropyltriethoxysilane (MPS) and tetraethoxylsilane/3
      aminopropyltriethoxysilane (APS). Another MIP-QD composite was synthesized by the
      chain-growth polymerization of methacrylic acid (MAA) and an allyl mercaptan
      linker. The prepared MIP-QDs were characterized by FTIR and SEM and utilized at
      0.33 mg/mL to determine the tetracycline content in phosphate buffers (pH 7.4,
      50mM) through the Perrin and Stern-Volmer models of quenching fluorometry. The
      Perrin model was applied to tetracycline concentrations of 7.4 MUM-0.37 mM for
      MIP-MPS-QD, 7.4 MUM-0.12 mM for MIP-APS-QD, and 7.4 MUM-0.10mM for MIP-MAA-QD
      (R(2)=0.9988, 0.9978, and 0.9931, respectively). The Stern-Volmer model was
      applied to tetracycline concentrations of 0.12-0.37 mM for MIP-APS-QD
      (R(2)=0.9983) and 0.10-0.37 mM for MIP-MAA-QD (R(2)=0.9970). The detection limits
      were 0.45 MUM, 0.54 MUM, and 0.50 MUM for MIP-MPS-QD, MIP-APS-QD, and MIP-MAA-QD,
      respectively. Equilibrium times, differences between imprinted and nonimprinted
      polymers, and MIP-QD quenching mechanisms were discussed. Finally, specificity
      studies demonstrated that MIP-MAA-QD exhibited optimal recoveries of 96% from
      bovine serum albumin (n=5, RSD=3.6%) and 91% from fetal bovine serum (n=5,
      RSD=4.8%).

PMID- 24934750
TI  - Autonomous capillary microfluidic system with embedded optics for improved
      troponin I cardiac biomarker detection.
AB  - Cardiovascular diseases are the most prevalent medical conditions affecting the
      modern world, reducing the quality of life for those affected and causing an ever
      increasing burden on clinical resources. Cardiac biomarkers are crucial in the
      diagnosis and management of patient outcomes. In that respect, such proteins are
      desirable to be measured at the point of care, overcoming the shortcomings of
      current instrumentation. We present a CO2 laser engraving technique for the rapid
      prototyping of a polymeric autonomous capillary system with embedded on-chip
      planar lenses and biosensing elements, the first step towards a fully
      miniaturised and integrated cardiac biosensing platform. The system has been
      applied to the detection of cardiac Troponin I, the gold standard biomarker for
      the diagnosis of acute myocardial infarction. The devised lab-on-a-chip device
      was demonstrated to have 24 pg/ml limit of detection, which is well within the
      minimum threshold for clinically applicable concentrations. Assays were completed
      within approximately 7-9 min. Initial results suggest that, given the
      portability, low power consumption and high sensitivity of the device, this
      technology could be developed further into point of care instrumentation useful
      in the diagnosis of various forms of cardiovascular diseases.

PMID- 24934753
TI  - Dissecting the steps of CO2 reduction: 1. The interaction of CO and CO2 with
      gamma-Al2O3: an in situ FTIR study.
AB  - The adsorption of CO2 and CO was investigated on a pure gamma-Al2O3 support
      material that has been used in Pd and Ru catalysts for the reduction of CO2. The
      adsorption of CO2 resulted in the formation of carbonates, bicarbonates and
      linearly adsorbed CO2 species. The amount and the nature of the adsorbed species
      were dependent on the annealing temperature of the alumina support. On gamma
      Al2O3 annealed at 473 K mostly bicarbonates formed, while no adsorbed CO2 was
      seen on this highly hydroxylated surface. With increasing calcination temperature
      the amount of both surface carbonates and linearly adsorbed CO2 increased, but
      still the most abundant surface species were bicarbonates. Surface carbonates and
      adsorbed CO2 can readily be removed from the alumina surface, while bicarbonates
      are stable to elevated temperatures. The interaction of CO with gamma-Al2O3 is
      much weaker than that of CO2. At room temperature CO adsorbs only on Lewis acid
      sites, and can be readily removed by evacuation. At 100 K CO can probe different
      defect sites on the alumina surface. Under no conditions we have observed the
      formation of any carbonates or bicarbonates upon the interaction of CO with the
      pure alumina support. In co-adsorption experiments CO competes for adsorption
      sites with the linearly adsorbed CO2 on the 773 K-annealed gamma-Al2O3 surface,
      but it does not result in the desorption of CO2, rather in the increased
      production of weakly held carbonates. After the removal of adsorbed CO, CO2 moves
      back to its original adsorption sites, i.e., Lewis acidic Al(3+) centers. The
      exposure of a CO2-saturated gamma-Al2O3 to H2O did not affect any of the adsorbed
      surface species. The findings of this study will be used to rationalize the
      results of our ongoing in situ and in operando studies on the reduction of CO2 on
      supported Pd and Ru catalysts. 

PMID- 24934754
TI  - Chicken or egg--Weismann revisited.

PMID- 24934751
TI  - AP-1 activation attenuates the arsenite-induced apoptotic response in human
      bronchial epithelial cells by up-regulating HO-1 expression.
AB  - Arsenite is a cytotoxic reagent that has been used clinically to treat certain
      cancers. Although the cytotoxic mechanisms of arsenite have been investigated,
      the cellular mechanisms that act against arsenite damage are poorly understood.
      Heme oxygenase 1 (HO-1) has been implicated in cellular survival under other
      multiple stress conditions. Here, we show that a significant induction of HO-1
      expression is present in human bronchial epithelial cells (Beas-2B) treated with
      lethal doses of arsenite treatment. This induction depends on the known ERK/AP1
      signaling pathway. As expected, HO-1 RNAi knockdown, or ERK/AP1 inhibition,
      renders the Beas-2B cells more sensitive to arsenite damage. Our data thus
      suggest that transcriptional upregulation of HO-1 expression via a putative
      ERK/AP-1 pathway constitutes an inherent mechanism by which arsenite-induced
      apoptosis is attenuated. 

PMID- 24934756
TI  - Newer clinically available antithrombotics and their antidotes.
AB  - New oral anticoagulants (NOACs) have emerged as an alternative therapy to
      warfarin in the treatment of arterial and venous thromboembolism and in stroke
      prevention in patients with non-valvular atrial fibrillation (AF). Three of them,
      i.e., dabigatran, rivaroxaban, and apixaban, have been approved for clinical use
      in North America and in a number of European countries. In non-valvular AF, their
      approval was based on large randomized trials showing that they are non-inferior
      or even, in some instances, superior to warfarin. Dabigatran is a direct thrombin
      (factor IIa) inhibitor; rivaroxaban and apixaban are direct factor Xa inhibitors.
      Before using NOACs, it is recommended to become familiar with their
      pharmacological characteristics and their metabolism. The absence of specific
      antidotes is often cited as part of the possible weaknesses of NOACs. Antidotes
      are perceived to be useful in emergency situations such as life-threatening
      bleeding or non-elective major surgery. NOACs do not require blood monitoring,
      and therefore, patient compliance to the treatment is essential. For the present
      time, there are no specific antidotes available for the three NOACs approved for
      clinical use. However, phase I or phase II research studies in this area are
      ongoing. For dabigatran, a specific antidote has been tested in a rat model of
      anticoagulation, and a study in healthy male volunteers has been recently
      reported. For rivaroxaban, prothrombin complex concentrates (PCCs) have been
      found to completely reverse the prolongation of the prothrombin time induced by
      this NOAC. For apixaban, recombinant factor VII was found in an experimental
      study using human blood to be superior to activated PCC (aPCC) and PCC. More
      specific antidotes for rivaroxaban and apixaban are in phases I and II
      evaluation. The management of patients suffering from a major bleeding or
      requiring a non-elective major surgery includes non-specific reversal agents and
      is discussed in the light of a recent position paper and of current literature.
      Most recommendations are based on expert opinions only as randomized trials using
      agents for reversal of anticoagulation in case of life-threatening bleeding or of
      major urgent surgery are not available. 

PMID- 24934755
TI  - Arabic-speaking migrants' experiences of the use of interpreters in healthcare: a
      qualitative explorative study.
AB  - INTRODUCTION: Arabic-speaking migrants have constituted a growing population in
      recent years. This entails major challenges to ensure good communication in the
      healthcare encounter in order to provide individual and holistic healthcare. One
      of the solutions to ensure good communication between patient and healthcare
      staff who do not share the same language is to use a professional interpreter. To
      our knowledge, no previous qualitative studies have been found concerning Arabic
      speaking migrants and the use of interpreters. This study aims to ascertain their
      individual experiences which can help extend our understanding of the studied
      area. METHOD: A purposive sample of 13 Arabic-speaking persons with experience of
      using interpreters in healthcare encounters. Data were collected between November
      2012 and March 2013 by four focus-group interviews and analysed with qualitative
      analysis according to a method described for focus groups. RESULTS: Four
      categories appeared from the analysis: 1) The professional interpreter as
      spokesperson; 2) Different types of interpreters and modes of interpretation
      adapting to the healthcare encounter; 3) The professional interpreter's task and
      personal properties affected the use of professional interpreters in a healthcare
      encounter; 4) Future planning of the use of professional interpreters in a
      healthcare encounter. The main findings were that the use of interpreters was
      experienced both as a possibility and as a problem. The preferred type of
      interpreters depended on the interpreter's dialect and ability to interpret
      correctly. Besides the professional interpreter's qualities of good skill in
      language and medical terminology, translation ability, neutrality and
      objectivity, Arabic-speaking participants stated that professional interpreters
      need to share the same origin, religion, dialect, gender and political views as
      the patient in order to facilitate the interpreter use and avoid inappropriate
      treatment. CONCLUSION: The study showed that the personal qualities of a good
      interpreter not only cover language ability but also origin, religion, dialect,
      gender and political views. Thus, there is need to develop strategies for
      personalized healthcare in order to avoid inappropriate communication, to satisfy
      the preferences of the person in need of interpreters and improve the impact of
      interpretation on the quality of healthcare.

PMID- 24934757
TI  - Phrenic nerve stimulation in cardiac resynchronization therapy.
AB  - In cardiac resynchronization therapy (CRT), the electrical impulse delivered by
      the left ventricular (LV) lead may incidentally cause phrenic nerve stimulation
      (PNS). The purpose of this state-of-the-art review is to describe the frequency,
      risk factors, and clinical consequences of PNS and to present the most recent
      options to successfully manage PNS. PNS occurs in 2 to 37% of implanted patients
      and is not always detected in the supine position during implantation. Lateral
      and posterior veins are at higher risk of PNS than anterior veins, and apical
      positions are at higher risk of PNS than basal positions. The management of PNS
      discovered during implantation may include mapping the course of the target vein
      in order to find a PNS-free site, targeting another vein if available, and pacing
      with alternative configurations before changing the lead location. Non-invasive
      options for management of post-operative PNS depend on the difference between PNS
      and LV stimulation thresholds and include reducing the LV pacing output,
      automatic determination of LV stimulation threshold and minimal output delivery
      by the device, increasing the pulse duration, and electronic repositioning. New
      quadripolar leads allow to pace from different cathodes, and the multiple pacing
      configurations available have proved superior to bipolar leads in mitigating PNS.
      This electronic repositioning addresses almost all of the clinically relevant PNS
      and should markedly reduce the need for invasive lead repositioning or CRT
      abandon, which is actually the last option for 2% of patients.

PMID- 24934758
TI  - Usefulness of QRS voltage correction by body mass index to improve
      electrocardiographic detection of left ventricular hypertrophy in patients with
      systemic hypertension.
AB  - Obesity reduces the accuracy of voltage-based electrocardiographic (ECG) criteria
      for diagnosis of left ventricular (LV) hypertrophy. We developed a new ECG score
      for diagnosis of LV hypertrophy, defined either by a typical strain pattern or a
      product of the Cornell voltage (R wave height in lead aVL plus S wave depth in
      lead V3) by body mass index >604 mm?kg/m(2). We examined a population of 2,747
      untreated hypertensive subjects (mean age 49 +/- 11 years) with good quality ECG
      and echocardiographic tracings. Several traditional ECG criteria for LV
      hypertrophy were compared with the new score, with echocardiographic LV mass
      taken as reference. Among the tested criteria, the highest sensitivity combined
      with specificity was yielded by the new score (sensitivity 36.1%, 95% confidence
      interval [CI] 32.9 to 39.4; specificity 90.5%, 95% CI 89.1 to 91.8; and accuracy
      73.1%, 95% CI 71.5 to 74.8). Prevalence of ECG LV hypertrophy with the new score
      was 18%. On the basis of comparisons between areas under the receiver operating
      characteristic curves, the best performance was achieved by the new score with
      respect to other ECG criteria for LV hypertrophy (all p <0.0001). In conclusion,
      correction of Cornell voltage by body mass index as a marker of obesity improves
      the performance of traditional electrocardiography for diagnosis of LV
      hypertrophy in patients with hypertension. 

PMID- 24934759
TI  - Cardiovascular magnetic resonance determinants of left ventricular noncompaction.
AB  - Insufficient precision remains in accurately identifying left ventricular
      noncompaction (LVNC) from the healthy normal morphologic spectrum. We aim to
      provide a better distinction between normal left ventricular trabeculations and
      LVNC. We used a previously well-defined cohort of 120 healthy volunteers for
      normal reference values of the trabecular/compacted ratio derived from a
      consistent selection of short-axis cardiovascular magnetic resonance images. We
      performed forward selection of logistic regression models, selecting the best
      model that was subsequently assessed for discrimination and calibration,
      validated, and converted into a clinical diagnostic chart to benchmark the
      boundaries of detection from a cohort of 30 patients considered to have LVNC. We
      showed that 3 combinations of a maximal end-diastolic trabecular/compacted ratio
      (>=1 [apex], >1.8 [midcavity]), (>2 [apex], >=0.6 [midcavity]), or (>0.5 [base],
      >1.8 [midcavity]) separate the cohorts with the highest accuracy (C statistic
      [95% confidence interval] of 0.9749 (0.9748 to 0.9751) for the diagnostic chart).
      Quantitative cardiovascular magnetic resonance also shows that patients
      considered to have LVNC have a significantly reduced ejection fraction compared
      with normal volunteers. At midcavity and apical level, it is difficult to
      identify papillary muscles that are replaced by a dense trabecular meshwork. In
      conclusion, we developed a new, refined, diagnostic tool for identifying LVNC,
      based on an a priori assessment of the trabecular architecture in healthy
      volunteers. 

PMID- 24934760
TI  - Proteinuria in adults with sickle-cell disease: the role of
      hydroxycarbamide(hydroxyurea) as a protective agent.
AB  - BACKGROUND: Renal abnormalities are often seen in sickle cell disease (SCD).
      OBJECTIVE: To investigate the role of hydroxycarbamide as a protective agent in
      sickle cell nephropathy. SETTING: Patients with SCD followed at a Hematology
      outpatients clinic. METHODS: Prospective study with 26 SCD patients. Renal
      function evaluation was performed and a comparison between patients and control
      group was done. Patients using hydroxycarbamide were compared to those not taking
      this drug. MAIN OUTCOME MEASURE: Effect of hydroxycarbamide on renal function.
      RESULTS: Patients mean age was 32.1 +/- 9.9 years, and 16 (61 %) were males.
      Glomerular hyperfiltration was found in nine patients with SCD (34.6 %). GFR < 60
      mL/min/1.73 m2 was observed in three cases (11.5 %). Microalbuminuria (30-300
      mg/day) was found in seven cases (27 %) and macroalbuminuria (>300 mg/dia) in one
      patient (3.8 %). All patients had urinary concentrating deficit, and inability to
      acidify urine was found in ten cases (38.4 %). The comparison of patients
      according to the use of hydroxycarbamide showed lower levels of serum creatinine
      in those using the drug (0.6 +/- 0.1 vs. 0.8 +/- 0.3 mg/dL, p = 0.03), as well as
      lower levels of 24 h-proteinuria (226 +/- 16 vs. 414 +/- 76 mg/dL, p = 0.0001),
      but not microalbuminuria (79 +/- 15 vs. 55 +/- 86 mg/dL, p = 0.35). CONCLUSION:
      SCD is associated with important renal abnormalities. Hydroxycarbamide seems to
      protect kidney function in SCD by decreasing proteinuria but not
      microalbuminuria.

PMID- 24934761
TI  - The immunomodulatory effect of propolis on receptors expression, cytokine
      production and fungicidal activity of human monocytes.
AB  - OBJECTIVES: Propolis is a beehive product and its immunomodulatory action has
      been documented; however, little is known concerning its mechanisms of action on
      human cells. Propolis influence on the initial events of the immune response was
      assessed, evaluating cell markers, cytokine production and the fungicidal
      activity of human monocytes. METHODS: Toll-like receptor (TLR)-2, TLR-4, human
      leukocyte antigen-DR and cluster of differentiation (CD)80 expression by human
      monocytes was assessed using a FACSCalibur flow cytometer, cytokine production
      (tumour necrosis factor (TNF)-alpha and interleukin (IL)-10) was determined by
      ELISA and the candidacidal activity was investigated after monocytes incubation
      with propolis and challenged with Candida albicans. The role of TLR-2 and TLR-4
      on propolis action was assessed as well. KEY FINDINGS: Propolis upregulated TLR-4
      and CD80 expression and affected TNF-alpha and IL-10 production, depending on
      concentration. Propolis also increased the fungicidal activity of monocytes.
      Cytokine production was decreased by blocking TLR-4, whereas the fungicidal
      activity was affected by blocking TLR-2. CONCLUSIONS: Propolis exerted an
      immunomodulatory action on cell receptors, cytokine production and fungicidal
      activity of human monocytes without affecting cell viability and depending on
      concentration. TLR-2 and TLR-4 may be involved in its mechanism of action.

PMID- 24934762
TI  - Association of TRPS1 gene with different EMT markers in ERalpha-positive and
      ERalpha-negative breast cancer.
AB  - BACKGROUND: Breast cancer is a heterogeneous disease consisting of different
      subtypes. Trichorhinophalangeal syndrome type 1 (TRPS1) gene, a GATA-type
      transcription factor, has been found to be highly expressed in breast cancer.
      Epithelial-to-mesenchymal transition (EMT) is known to play an important role in
      tumour invasion and metastasis. Our objective was to elucidate the different
      roles and clinical relevance of TRPS1 in different estrogen receptor (ER)
      expression subtypes of breast cancer. METHODS: An immunohistochemical study was
      performed. The correlation between clinicopathological features and other
      biomarker profiles were analysed statistically. RESULT: TRPS1 expression was
      correlated with the patients' age (P=0.017). It was positively related with
      ERalpha (P<0.001), progesterone receptor (PR) (P<0.001) and ERbeta (P=0.001)
      status, but negatively associated with Ki67 (P=0.002) and HER2 (P=0.025) status.
      In ERalpha-positive breast cancer, TRPS1 expression was positively associated
      with the expression of E-cadherin (P<0.001), beta-catenin(P=0.001), ERbeta
      (P=0.03), and p53 (P=0.002) status, while in ERalpha-negative breast cancer,
      TRPS1 expression was correlated with slug (P=0.004), vimentin (P=0.003), smooth
      muscle actin (SMA) (P=0.031), and IMP3 (P=0.005) expression. CONCLUSIONS: Based
      on our findings, we conclude that TRPS1 is positively associated with E-cadherin
      and beta-catenin status in ERalpha-positive breast cancer cells, while it is also
      significantly associated with mesenchymal markers of EMT in ERalpha-negative
      breast cancer cells. TRPS1 can be a prognostic marker depending on the type of
      breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/8686515681264281.

PMID- 24934764
TI  - Recent trends for novel options in experimental biological therapy of beta
      thalassemia.
AB  - INTRODUCTION: beta-thalassemias are caused by nearly 300 mutations of the beta
      globin gene, leading to low or absent production of adult hemoglobin.
      Achievements have been recently obtained on innovative therapeutic strategies for
      beta-thalassemias, based on studies focusing on the transcriptional regulation of
      the gamma-globin genes, epigenetic mechanisms governing erythroid
      differentiation, gene therapy and genetic correction of the mutations. AREAS
      COVERED: The objective of this review is to describe recently published
      approaches (the review covers the years 2011 - 2014) useful for the development
      of novel therapeutic strategies for the treatment of beta-thalassemia. EXPERT
      OPINION: Modification of beta-globin gene expression in beta-thalassemia cells
      was achieved by gene therapy (eventually in combination with induction of fetal
      hemoglobin [HbF]) and correction of the mutated beta-globin gene. Based on recent
      areas of progress in understanding the control of gamma-globin gene expression,
      novel strategies for inducing HbF have been proposed. Furthermore, the
      identification of microRNAs involved in erythroid differentiation and HbF
      production opens novel options for developing therapeutic approaches for beta
      thalassemia and sickle-cell anemia.

PMID- 24934763
TI  - Senescence impairs direct conversion of human somatic cells to neurons.
AB  - Recent reports have shown that fibroblasts can be converted to neurons by forced
      expression of transcription factors. However, the mechanisms underlying this
      conversion remain unclear. Here, we show that the efficiency of neuronal
      conversion of embryonic human fibroblasts aged in culture is lower than that in
      cells in early culture stages. Moreover, depletion of p16(Ink4a) and p19(Arf)
      involved in the activation of cellular senescence is sufficient to convert human
      fibroblast and epithelial cells into neurons. The induced neurons express neuron
      specific proteins, generate action potentials and neurotransmitter receptor
      mediated currents. Genome-wide transcriptional analysis shows that the induced
      neurons have a profile different from fibroblasts and similar to that of control
      neurons induced by established methods. We further noted that expression of p53
      blocks the neuronal conversion, whereas expression of human telomerase reverse
      transcriptase (hTERT) induces it. Our results indicate that overcoming senescence
      is a crucial step for neuronal conversion of somatic cells. 

PMID- 24934765
TI  - Purification, characterization, and in vitro activity of 2,4-Di-tert-butylphenol
      from Pseudomonas monteilii PsF84: conformational and molecular docking studies.
AB  - A novel strain of Pseudomonas monteilii, PsF84, was isolated from tannery waste
      soil from Jajmau, Kanpur, India. 16S rRNA gene sequence phylogenetic analysis
      confirmed the taxonomic affiliation of PsF84 as P. monteilii. An antifungal
      volatile organic compound (VOC) active against hyphal growth of Fusarium
      oxysporum (CIMAP-IMI-357464) in vitro was isolated from strain PsF84 by using
      chromatographic techniques. The molecular formula of the antifungal VOC was
      deduced to be C14H22O by EI-MS and 1D and 2D NMR spectral analysis. 2,4-Di-tert
      butylphenol was found to be effective against an agriculturally important fungus,
      namely, F. oxysporum, in inhibiting spore germination and hyphal growth.
      Molecular docking analysis of 2,4-di-tert-butylphenol with beta-tubulin further
      validated the potential of beta-tubulin binding in F. oxysporum. Two residues of
      beta-tubulin protein, HIS 118 and THR 117, showed hydrogen binding with ligand.
      To the authors' knowledge, this is the first report of antifungal VOC (2,4-di
      tert-butylphenol) produced by P. monteilii PsF84 that can be a potent inhibitor
      of beta-tubulin of F. oxysporum.

PMID- 24934766
TI  - [Therapeutic targeted approaches on androgen receptors in prostate cancer].
AB  - The treatment of metastatic prostate cancer since the 1940s is based on the
      consideration of oncogenic addiction to its androgen receptor (AR). The
      significant improvement in survival outcomes over the past decade depends not
      only on the development of effective cytotoxic chemotherapy but also new
      molecules targeting the AR or decreasing testosterone levels, even in case of
      castration-resistant cancer. In this review, we summarize the structure and
      function of the RA, the mechanisms of androgen suppression, the concept of
      resistance to castration, historical targeted treatment on the AR and those
      recently marketed as abiraterone acetate and enzalutamide. 

PMID- 24934767
TI  - Correlating Rubisco catalytic and sequence diversity within C3 plants with
      changes in atmospheric CO2 concentrations.

PMID- 24934768
TI  - [How i do... intrauterine balloon tamponade for postpartum haemorrhage].

PMID- 24934769
TI  - [48,XXYY men with azoospermia: how to manage infertility?].
AB  - 48,XXYY syndrome is a rare form of sex chromosomal aneuploidy. Usually considered
      as a variant of Klinefelter syndrome because of shared features (azoospermia,
      tall stature, hypergonadotropic hypogonadism), it is a separate entity because
      diagnostic is currently made in prepubertal boy with neuro-psychological
      disorders. We here report the case of a 48,XXYY patient consulting for adult
      infertility and the indication to perform testicular sperm extraction is
      discussed. 

PMID- 24934770
TI  - [Rare case of bilateral pulmonary agenesis and prenatal diagnosis].
AB  - Bilateral pulmonary agenesis (BPA) is a rare congenital lung malformation. The
      prognosis is severe as it is incompatible with extra-uterine life. Although
      multiple prenatal imaging modalities are developed, the prenatal diagnosis of BPA
      remains problematic. We report a case of BPA observed in our unity and for which
      the diagnosis was not clearly identified during the evaluation. This report
      illustrates the need to consider all the imaging aspects and particularly during
      US examination suspecting BPA. 

PMID- 24934771
TI  - [How I do... to reduce the laparotomy incision size by means of an obstetrical
      technique].

PMID- 24934773
TI  - Prevalence and potential causes of epilepsy in Nigeria.

PMID- 24934772
TI  - Interactive XCMS Online: simplifying advanced metabolomic data processing and
      subsequent statistical analyses.
AB  - XCMS Online (xcmsonline.scripps.edu) is a cloud-based informatic platform
      designed to process and visualize mass-spectrometry-based, untargeted metabolomic
      data. Initially, the platform was developed for two-group comparisons to match
      the independent, "control" versus "disease" experimental design. Here, we
      introduce an enhanced XCMS Online interface that enables users to perform
      dependent (paired) two-group comparisons, meta-analysis, and multigroup
      comparisons, with comprehensive statistical output and interactive visualization
      tools. Newly incorporated statistical tests cover a wide array of univariate
      analyses. Multigroup comparison allows for the identification of differentially
      expressed metabolite features across multiple classes of data while higher order
      meta-analysis facilitates the identification of shared metabolic patterns across
      multiple two-group comparisons. Given the complexity of these data sets, we have
      developed an interactive platform where users can monitor the statistical output
      of univariate (cloud plots) and multivariate (PCA plots) data analysis in real
      time by adjusting the threshold and range of various parameters. On the
      interactive cloud plot, metabolite features can be filtered out by their
      significance level (p-value), fold change, mass-to-charge ratio, retention time,
      and intensity. The variation pattern of each feature can be visualized on both
      extracted-ion chromatograms and box plots. The interactive principal component
      analysis includes scores, loadings, and scree plots that can be adjusted
      depending on scaling criteria. The utility of XCMS functionalities is
      demonstrated through the metabolomic analysis of bacterial stress response and
      the comparison of lymphoblastic leukemia cell lines.

PMID- 24934774
TI  - Assessment of pharmacokinetics and tolerability of intranasal diazepam relative
      to rectal gel in healthy adults.
AB  - Diazepam rectal gel (RG) is currently the only approved rescue therapy for
      outpatient management of seizure clusters in the United States. There is an unmet
      medical need for an alternative rescue therapy for seizure clusters that is
      effective, and more convenient to administer with a socially acceptable method of
      delivery. An intranasal diazepam formulation has been developed, and this study
      evaluates the tolerability and bioavailability of diazepam nasal spray (NS)
      relative to an equivalent dose of diazepam-RG in healthy adults. Twenty-four
      healthy adults were enrolled in a phase 1, open-label, 3-period crossover study.
      Plasma diazepam and metabolite concentrations were measured by serial sampling.
      Dose proportionality for 5- and 20-mg intranasal doses and the bioavailability of
      20mg diazepam-NS relative to 20mg diazepam-RG were assessed by maximum plasma
      concentration (Cmax) and systemic exposure parameters (AUC0-infinity and AUC0
      24). The mean Cmax values for 20mg diazepam-NS and 20mg diazepam-RG were 378 +/-
      106 and 328 +/- 152 ng/mL, achieved at 1.0 and 1.5h, respectively. Subjects
      administered intranasal and rectal gel formulations experienced nasal and rectal
      leakage, respectively. Diazepam absorption following intranasal administration
      was consistent but 3 subjects with diazepam-RG had low plasma drug levels at the
      earliest assessment of 5 min, due to poor retention, and were excluded from
      analysis. Excluding them, the treatment ratios (20mg diazepam-NS:20mg diazepam
      RG) and 90% confidence intervals for diazepam Cmax and AUC0-24 were 0.98 (0.85
      1.14) and 0.89 (0.80-0.98), respectively, suggesting that the bioavailability was
      comparable between the two formulations. Dose proportionality was observed
      between the lowest and highest dose-strengths of intranasal formulation. Both
      intranasal and rectal treatments were well tolerated with mild to moderate
      adverse events. Results suggest that a single-dose of 20mg diazepam-NS is
      tolerable and comparable in bioavailability to that of diazepam-RG. The
      intranasal formulation may provide caregivers and patients with a more socially
      acceptable and convenient alternative rescue therapy in the acute treatment of
      seizure clusters.

PMID- 24934775
TI  - Detection of short tandem repeat polymorphisms from human nails using direct
      polymerase chain reaction method.
AB  - Human nail is an important forensic material for parental testing and individual
      identification in large-scale disasters. Detection of STR polymorphism from hard
      tissues generally requires DNA purification, which is technically complicated and
      time consuming. In the present study, we attempted to detect STR polymorphisms
      from untreated human nail samples by direct PCR amplification method using the
      primer mixture supplied with the GenePrint(r) SilverSTR(r) III System or the
      AmpFlSTR(r) Identifiler(r) PCR Amplification Kit, and Tks Gflex DNA polymerase
      known to be effective for amplification from crude samples. A nail fragment
      measuring approximately 1.5 mm in breadth and 0.5 mm in length was placed
      directly into a PCR tube, and various PCR conditions were tested. The PCR
      products were analyzed by denaturing acrylamide gel electrophoresis or CE.
      Multiple STR polymorphisms were detected successfully. This method that detects
      STR polymorphisms not only from fresh human fingernails, but also from old nail
      fragments stored at room temperature for up to 10 years is expected to become a
      novel DNA analytical method in forensic medicine and genetic studies. 

PMID- 24934776
TI  - Sustained Complete Molecular Remission After Discontinuation of Tyrosine Kinase
      Inhibitors in Blast-Phase Chronic Myeloid Leukemia.

PMID- 24934777
TI  - Reply to A.E. Mazzucco.

PMID- 24934778
TI  - Next steps for breast implant-associated anaplastic large-cell lymphoma.

PMID- 24934779
TI  - Epidermal Growth Factor Receptor P753S Mutation in Cutaneous Squamous Cell
      Carcinoma Responsive to Cetuximab-Based Therapy.

PMID- 24934780
TI  - Managing advanced colorectal cancer: have we reached the PEAK with current
      therapies?

PMID- 24934781
TI  - Aromatase Inhibitor Therapy As Effective Rescue in a Patient With Tamoxifen
      Refractory Metastatic Granulosa Cell Tumor of the Ovary.

PMID- 24934782
TI  - How well does supplemental screening magnetic resonance imaging work in high-risk
      women?

PMID- 24934783
TI  - Randomized trial of a telephone-based weight loss intervention in postmenopausal
      women with breast cancer receiving letrozole: the LISA trial.
AB  - PURPOSE: Obesity is associated with poor outcomes in women with operable breast
      cancer. Lifestyle interventions (LIs) that help women reduce their weight may
      improve outcomes. PATIENTS AND METHODS: We conducted a multicenter randomized
      trial comparing mail-based delivery of general health information alone or
      combined with a 24-month standardized, telephone-based LI that included diet (500
      to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of
      moderate-intensity physical activity per week) goals to achieve weight loss (up
      to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a
      body mass index (BMI) >= 24 kg/m(2) were eligible. Weight was measured in the
      clinic, and self-report physical activity, quality-of-life (QOL), and diet
      questionnaires were completed. The primary outcome was disease-free survival.
      Accrual was terminated at 338 of 2,150 planned patients because of loss of
      funding. RESULTS: Mean weight loss was significantly (P < .001) greater in the LI
      arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v
      0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI
      24 to < 30 v >= 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss
      was greatest in those with higher baseline levels of moderate-intensity physical
      activity or improvement in QOL. Hospitalization rates and medical events were
      similar. CONCLUSION: A telephone-based LI led to significant weight loss that was
      still evident at 24 months, without adverse effects on QOL, hospitalizations, or
      medical events. Adequately powered randomized trials with cancer end points are
      needed.

PMID- 24934784
TI  - Reply to M.C. Chamberlain.

PMID- 24934785
TI  - Weight loss interventions and breast cancer survival: the time is now.

PMID- 24934788
TI  - Twenty-twenty hindsight: an adjuvant breast cancer trial through the
      retrospectoscope.

PMID- 24934786
TI  - Frailty and adherence to adjuvant hormonal therapy in older women with breast
      cancer: CALGB protocol 369901.
AB  - PURPOSE: Most patients with breast cancer age >= 65 years (ie, older patients)
      are eligible for adjuvant hormonal therapy, but use is not universal. We examined
      the influence of frailty on hormonal therapy noninitiation and discontinuation.
      PATIENTS AND METHODS: A prospective cohort of 1,288 older women diagnosed with
      invasive, nonmetastatic breast cancer recruited from 78 sites from 2004 to 2011
      were included (1,062 had estrogen receptor-positive tumors). Interviews were
      conducted at baseline, 6 months, and annually for up to 7 years to collect
      sociodemographic, health care, and psychosocial data. Hormonal initiation was
      defined from records and discontinuation from self-report. Baseline frailty was
      measured using a previously validated 35-item scale and grouped as prefrail or
      frail versus robust. Logistic regression and proportional hazards models were
      used to assess factors associated with noninitiation and discontinuation,
      respectively. RESULTS: Most women (76.4%) were robust. Noninitiation of hormonal
      therapy was low (14%), but in prefrail or frail (v robust) women the odds of
      noninitiation were 1.63 times as high (95% CI, 1.11 to 2.40; P = .013) after
      covariate adjustment. Nonwhites (v whites) had higher odds of noninitiation (odds
      ratio, 1.71; 95% CI, 1.04 to 2.80; P = .033) after covariate adjustment. Among
      initiators, the 5-year continuation probability was 48.5%. After adjustment, the
      risk of discontinuation was higher with increasing age (P = .005) and lower for
      stage >= IIB (v stage I) disease (P = .003). CONCLUSION: Frailty is associated
      with noninitiation of hormonal therapy, but it does not seem to be a major
      predictor of early discontinuation in older patients.

PMID- 24934789
TI  - Forecasting unanticipated consequences of "The Sunshine Act": mostly cloudy.

PMID- 24934787
TI  - Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as
      adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes:
      CALGB 40101 (Alliance).
AB  - PURPOSE: Optimal adjuvant chemotherapy for early-stage breast cancer balances
      efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T)
      was inferior to doxorubicin and cyclophosphamide (AC), when each was administered
      for four or six cycles of therapy, and whether it offered less toxicity. PATIENTS
      AND METHODS: Patients with operable breast cancer with 0 to 3 positive nodes were
      enrolled onto the study to address the noninferiority of single-agent T to AC,
      defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T
      versus AC less than 1.30 for the primary end point of relapse-free survival
      (RFS). As a 2 * 2 factorial design, duration of therapy was also addressed and
      was previously reported. RESULTS: With 3,871 patients enrolled onto the trial, a
      median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of
      1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of
      noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for
      overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute
      advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All
      nine treatment-related deaths were patients receiving AC and are included in the
      analyses of both RFS and OS. Hematologic toxicity was more common in patients
      treated with AC, and neuropathy was more common in patients treated with T.
      CONCLUSION: This trial did not show noninferiority of T to AC, a conclusion that
      is unlikely to change with additional events and follow-up. T was less toxic than
      AC.

PMID- 24934790
TI  - Is there a role for vascular endothelial growth factor receptor 2 inhibitors in
      glioblastoma?

PMID- 24934791
TI  - Onco-nephrology: an invitation to a new field.

PMID- 24934792
TI  - The heritability of cancer.

PMID- 24934794
TI  - Needle biopsy for breast cancer diagnosis: a quality metric for breast surgical
      practice.

PMID- 24934793
TI  - Effectiveness of screening with annual magnetic resonance imaging and
      mammography: results of the initial screen from the ontario high risk breast
      screening program.
AB  - PURPOSE: The Ontario Breast Screening Program expanded in July 2011 to screen
      women age 30 to 69 years at high risk for breast cancer with annual magnetic
      resonance imaging (MRI) and digital mammography. To the best of our knowledge,
      this is the first organized screening program for women at high risk for breast
      cancer. PATIENTS AND METHODS: Performance measures after assessment were compared
      with screening results for 2,207 women with initial screening examinations. The
      following criteria were used to determine eligibility: known mutation in BRCA1,
      BRCA2, or other gene predisposing to a markedly increased risk of breast cancer,
      untested first-degree relative of a gene mutation carrier, family history
      consistent with hereditary breast cancer syndrome and estimated personal lifetime
      breast cancer risk >= 25%, or radiation therapy to the chest (before age 30 years
      and at least 8 years previously). RESULTS: The recall rate was significantly
      higher among women who had abnormal MRI alone (15.1%; 95% CI, 13.8% to 16.4%)
      compared with mammogram alone (6.4%; 95% CI, 5.5% to 7.3%). Of the 35 breast
      cancers detected (16.3 per 1,000; 95% CI, 11.2 to 22.2), none were detected by
      mammogram alone, 23 (65.7%) were detected by MRI alone (10.7 per 1,000; 95% CI,
      6.7 to 15.8), and 25 (71%) were detected among women who were known gene mutation
      carriers (30.8 per 1,000, 95% CI, 19.4 to 43.7). The positive predictive value
      was highest for detection based on mammogram and MRI (12.4%; 95% CI, 7.3% to
      19.3%). CONCLUSION: Screening with annual MRI combined with mammography has the
      potential to be effectively implemented into an organized breast screening
      program for women at high risk for breast cancer. This could be considered an
      important management option for known BRCA gene mutation carriers.

PMID- 24934795
TI  - Prevalence of soil-transmitted helminths after mass albendazole administration in
      an indigenous community of the Manu jungle in Peru.
AB  - Few data are available on the epidemiology of soil-transmitted helminths (STHs)
      in indigenous populations of the Peruvian Amazon. While albendazole is being
      increasingly used in deworming campaigns, few data exist on the impact of mass
      drug administration in isolated populations. We studied the prevalence of STHs,
      anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon.
      Participants had received two doses of albendazole on consecutive days, 3 months
      before and again 2 weeks before data collection. Overall, 290 subjects were
      included. Most were female (53.7%) and 63.9% were <=19 years old. Half of the
      participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%),
      Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other
      helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5
      19 years (51.8 %) and 20-35 years (68.6 %) old had helminths more often than
      those under 5 years (38%) and older than 35 years (41.5%) (P  =  0.02). Anemia
      was detected in 41% of children and this was more common in children under 5
      years that in those of 5-19 years [odd ratio (OR) = 5.68; 95% CI: 2.71-11.88].
      Overall, 72.1% of children were malnourished. Stunting was common in children
      (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration,
      this population continued to have a high prevalence of STHs, anemia, and
      malnutrition. In addition, we detected unusual organisms and organisms that do
      not respond to albendazole. Further studies are needed to assess the rationale
      and efficacy of mass chemotherapy for STHs in the Amazon.

PMID- 24934796
TI  - Presence of potentially pathogenic free-living amoebae strains from well water
      samples in Guinea-Bissau.
AB  - Free-living amoebae (FLA) include opportunistic pathogens such as Naegleria
      fowleri, Balamuthia mandrillaris, and the genera Sappinia and Acanthamoeba. In
      this study, a survey was conducted in order to evaluate the presence of
      potentially pathogenic amoebic strains in water samples collected from wells
      located in the western part of Guinea-Bissau. The samples were left to
      precipitate for 48 hours and then the sediments were seeded on non-nutrient agar
      plates containing Escherichia coli spread and cultures were checked daily for the
      presence of FLA. Identification of FLA strains was based on the morphological and
      polymerase chain reaction (PCR) using the 18S rDNA or 16S mitochondrial rDNA
      genes in the case of Naegleria and Balamuthia genera, respectively. In the case
      of positive samples of Acanthamoeba, strains were further classified at the
      genotype level by sequencing the diagnostic fragment 3 (DF3) region located in
      the 18S rDNA gene as previously described. Sappinia sp. was not isolated during
      the study and thus, no molecular analysis was performed for this genus. The
      obtained results revealed the presence of Acanthamoeba (genotypes T3 and T4),
      Naegleria fowleri, and Balamuthia mandrillaris. To the best of our knowledge,
      this is the first report demonstrating the presence of FLA in water bodies from
      Guinea-Bissau and the first report on the isolation of Balamuthia mandrillaris
      from environmental sources in Africa.

PMID- 24934797
TI  - Incidentally detected increased FDG uptake in bowel and its correlation with
      hystopathological data: our experience in a case series study.
AB  - When an intense intestinal FDG accumulation occurs, especially if focal, it can
      be referred to either physiological intestinal activity or bowel disease, thus
      leading to a radical change in patient's prognosis. Within a year, we recommended
      a colonoscopy to 103 of 7365 patients who were subjected to a total body FDG
      PET/CT. In a case-series study, we re-evaluated the patients and their lesions if
      already investigated with colonoscopy and biopsy. Only 18 patients were included
      in our study, but in none of them biopsy was negative and 3 adenocarcinomas, 8
      adenomas, 5 inflammatory patterns, 1 hyperplastic polyp and 1 eosinophilic
      infiltrate were diagnosed. In 16 patients, no suspicion was present and diagnosis
      was absolutely incidental. Besides, among the three major groups
      (adenocarcinomas, adenomas and phlogosis), SUVmax values were significantly
      different. Adenocarcinomas are linked with high SUVmax values (ranging from 8.3
      to 20.2) and large size (ranging from 26 to 43 mm). PET/CT sensitivity is low in
      detecting adenomas, being 71.4% if they are larger than 6 mm and 50% if SUVmax is
      lower than 4.9. SUVmax values in inflammatory lesions can range from 5.7 to 12.
      Colorectal cancer is still the second leading cause of cancer death, for this
      reason in many countries screening programs have been approved and colonoscopy is
      considered the golden standard. PET/CT cannot be considered as a screening test,
      but if it incidentally reveals intestinal abnormalities, this data cannot be
      underestimated and colonoscopy is highly recommended. 

PMID- 24934798
TI  - An improved Doppler model for obtaining accurate maximum blood velocities.
AB  - Maximum blood velocity estimates are frequently required in diagnostic
      applications, including carotid stenosis evaluation, arteriovenous fistula
      inspection, and maternal-fetal examinations. However, the currently used methods
      for ultrasound measurements are inaccurate and often rely on applying heuristic
      thresholds to a Doppler power spectrum. A new method that uses a mathematical
      model to predict the correct threshold that should be used for maximum velocity
      measurements has recently been introduced. Although it is a valuable and
      deterministic tool, this method is limited to parabolic flows insonated by
      uniform pressure fields. In this work, a more generalized technique that
      overcomes such limitations is presented. The new approach, which uses an extended
      Doppler spectrum model, has been implemented in an experimental set-up based on a
      linear array probe that transmits defocused steered waves. The improved model has
      been validated by Field II simulations and phantom experiments on tubes with
      diameters between 2mm and 8mm. Using the spectral threshold suggested by the new
      model significantly higher accuracy estimates of the peak velocity can be
      achieved than are now clinically attained, including for narrow beams and non
      parabolic velocity profiles. In particular, an accuracy of +1.2+/-2.5 cm/s has
      been obtained in phantom measurements for velocities ranging from 20 to 80 cm/s.
      This result represents an improvement that can significantly affect the way
      maximum blood velocity is investigated today.

PMID- 24934799
TI  - A physics-based temperature model for ultrasonic vibration-assisted pelleting of
      cellulosic biomass.
AB  - Temperature in ultrasonic vibration-assisted (UV-A) pelleting of cellulosic
      biomass has a significant impact on pellet quality. However, there are no reports
      on temperature models for UV-A pelleting of cellulosic biomass. The development
      of a physics-based temperature model can help to explain experimentally
      determined relations between UV-A pelleting process variables and temperature,
      and provide guidelines to optimize these process variables in order to produce
      pellets of good quality. This paper presents such a model for UV-A pelleting of
      cellulosic biomass. Development of the model is described first. Then temperature
      distribution is investigated using the model, and temperature difference between
      the top and the bottom surfaces of a pellet is explained. Based on this model,
      relations between process variables (ultrasonic power and pelleting duration) and
      temperature are predicted. Experiments were conducted for model verification, and
      the results agreed well with model predictions. 

PMID- 24934800
TI  - Improvements in elbow motion after resection of heterotopic bone: a systematic
      review.
AB  - Complex elbow trauma, severe burn, or a closed head injury render patients at
      risk for developing heterotopic ossification around the elbow. When heterotopic
      ossification restricts elbow motion, some patients request surgical resection. We
      performed a systematic review of the literature to analyze improvement in elbow
      motion after resection of heterotopic ossification around the elbow. We found
      that, on average, etiology had little impact on outcome after resection of
      heterotopic ossification. Resection of heterotopic bone generally leads to
      improvement of elbow function. 

PMID- 24934801
TI  - High-yielding sequential one-pot synthesis of chiral and achiral alpha
      substituted acrylates via a metal-free reductive coupling reaction.
AB  - A general process for the high-yielding synthesis of substituted chiral and
      achiral alpha-substituted acrylates was achieved through the sequential one-pot
      combination of a metal-free reductive coupling reaction followed by an
      Eschenmoser methylenation. The proline catalyzed reaction of Meldrum's acid,
      aldehydes and Hantzsch ester followed by methylenation was successful with
      Eschenmoser's salt in the presence of an alcohol solvent. Herein, we have shown
      the high-yielding synthesis of privileged building blocks from chiral/achiral
      alpha-substituted acrylates and shown them to be very good intermediates in the
      pharmaceuticals and natural products synthesis. 

PMID- 24934802
TI  - Radiochemical pharmacokinetic profile of P10 peptide with antifungal properties.
AB  - Paracoccidioidomycosis (PCM) is a chronic granulomatous disease that is caused by
      the thermally dimorphic fungus Paracoccidioides brasiliensis. It is endemic in
      some countries of Latin America and can cause a high-burden fungal infection with
      significant morbidity and mortality. The peptide P10, which demonstrates immune
      protection against experimental PCM, was radiolabeled with a radioisotope and
      evaluated in vivo. The radiolabeling was conducted to trace the pharmacokinetics
      of the molecule in principal organs and tissues. This was achieved with high
      radiochemical purity. Biodistribution and scintigraphic imaging showed fast blood
      clearance that was mainly renal; however, hepatobiliar excretion was also, with
      marked uptake in cervical lymph nodes. This profile may be useful for the
      development of a prophylactic drug or vaccine for patients exposed to PCM. 

PMID- 24934803
TI  - Uncommon opportunistic yeast bloodstream infections from Qatar.
AB  - Eleven uncommon yeast species that are associated with high mortality rates
      irrespective of antifungal therapy were isolated from 17/187 (201 episodes)
      pediatric and elderly patients with fungemia from Qatar. The samples were taken
      over a 6-year period (January 2004-December 2010). Isolated species included
      Kluyveromyces marxianus, Lodderomyces elongisporus, Lindnera fabianii, Candida
      dubliniensis, Meyerozyma guilliermondii, Candida intermedia, Pichia kudriavzevii,
      Yarrowia lipolytica, Clavispora lusitaniae, Candida pararugosa, and
      Wickerhamomyces anomalus. Matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry provided correct identifications compared with molecular
      analysis testing of the same isolates. Low minimal inhibitory concentrations were
      found when isavuconazole and voriconazole were used for all uncommon yeast
      species evaluated in this study. Resistance to antifungal drugs was low and
      remained restricted to a few species. 

PMID- 24934804
TI  - Interindividual variability and intraindividual stability of oral fungal
      microbiota over time.
AB  - Oral microbiota is one of the most complex and diverse microbial communities in
      the human body. In the present study, we aimed to characterize oral fungi
      biodiversity and stability over time in a group of healthy participants with good
      oral health. Oral health and oral fungal microbiota were evaluated in 40 healthy
      individuals. A follow-up of 10 participants was carried out 28 weeks and 30 weeks
      after the first sampling. Oral rinse was collected and incubated in a fungal
      selective medium at 25oC and 37oC for 7 days. Fungi were identified based on
      macro- and microscopic morphology. API/ID32C was used for yeast identification,
      and molecular techniques were used to identify the most prevalent nonidentified
      moulds, mainly by sequencing 18S and internally transcribed spacer regions.
      Moulds were recovered from all participants and yeast from 92.5%. The most
      frequently isolated fungi were Candida spp., Rhodotorula spp., Penicillium spp.,
      Aspergillus spp., and Cladosporium spp. The oral fungal community presented a
      high interindividual variability, but the frequency and quantification of each
      fungal taxon was constant over the 30-week observation period, showing a
      consistent intraindividual stability over time. The intraindividual stability
      opposed to interindividual variability may suggest a common and a variable group
      of fungi in the oral cavity. 

PMID- 24934805
TI  - Characteristic and clinical relevance of Candida mannan test in the diagnosis of
      probable invasive candidiasis.
AB  - The gold standard laboratory tests used to diagnose invasive Candida infection
      (ICI) are based on the in vitro culture of blood or samples from other sterile
      sites. However, these tests have limited sensitivity (Se) and are generally not
      diagnostic until late in the infectious process. The Serion Candida mannan kit
      was evaluated for the diagnosis of ICI at Grenoble University Hospital (France)
      between 2007 and 2011. The results were then compared with worldwide data
      published between 1997 and 2011. This retrospective study was based on follow-up
      from the investigation of 162 patients of whom 91 had proven ICI; 13 had Candida
      colonization index (CCI) scores >=0.42, positive mannan tests, with
      nonconcomitant infections; and 58 had no evidence of Candida infection. Candida
      albicans, C. glabrata, C. tropicalis, and C. parapsilosis were the etiologic
      agents in 104 patients. For patients with or without ICI, the 12-week mortality
      rates were 35/104 (33.7%) and 6/58 (10.3%), respectively. The mannan diagnostic
      specificity was 51% and Se was 77%. However, in the meta-analysis (n = 1,536),
      values were 86% and 62%, respectively. Positive mannan test results may appear
      early (median 6 days) in the development of candidemia and have moderate
      diagnostic value for ICI, with a negative predictive value of 83%. In patients at
      risk of ICI with negative candidemia, the combination of Candida mannan test data
      with a CCI score >=0.42 may improve the diagnosis of probable ICI.

PMID- 24934806
TI  - Melanocytes and melanin represent a first line of innate immunity against Candida
      albicans.
AB  - Melanocytes are dendritic cells located in the skin and mucosae that synthesize
      melanin. Some infections induce hypo- or hyperpigmentation, which is associated
      with the activation of Toll-like receptors (TLRs), especially TLR4. Candida
      albicans is an opportunist pathogen that can switch between blastoconidia and
      hyphae forms; the latter is associated with invasion. Our objectives in this
      study were to ascertain whether C. albicans induces pigmentation in melanocytes
      and whether this process is dependent on TLR activation, as well as relating this
      with the antifungal activity of melanin as a first line of innate immunity
      against fungal infections. Normal human melanocytes were stimulated with C.
      albicans supernatants or with crude extracts of the blastoconidia or hyphae
      forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the
      melanosomal antigens Melan-A and gp100 was examined for any correlation with
      increased melanin levels or antifungal activity in melanocyte lysates.
      Melanosomal antigens were induced earlier than cell pigmentation, and hyphae
      induced stronger melanization than blastoconidia. Notably, when melanocytes were
      stimulated with crude extracts of C. albicans, the cell surface expression of
      TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time,
      blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced
      TLR4 expression. Taken together, these results suggest that melanocytes play a
      key role in innate immune responses against C. albicans infections by recognizing
      pathogenic forms of C. albicans via TLR4, resulting in increased melanin content
      and inhibition of infection. 

PMID- 24934807
TI  - Interferon-based treatment for patients with mycosis fungoides and hepatitis C
      virus infection: a case series.
AB  - BACKGROUND: Interferon (IFN) is a treatment option for both mycosis fungoides
      (MF) and hepatitis C virus (HCV) infection. Chemotherapy and anti-HCV treatment
      are generally not administered concurrently for fear of overlapping side effects.
      OBJECTIVE: Herein, we report on a subset of patients who received IFN-containing
      therapy for MF and HCV infection simultaneously. We aimed to evaluate whether
      concomitant treatment for MF and HCV is effective and well tolerated. METHODS: We
      reviewed the records of patients who were seen at MD Anderson Cancer Center from
      2008 to 2013 with histologically confirmed MF and chronic HCV infection, and were
      treated with simultaneous focus on both diseases. RESULTS: Six HCV-infected
      patients with MF received simultaneous anti-HCV and anti-MF treatment with IFN
      containing therapy. Two patients achieved sustained virological response
      (regarded as virological cure). They both received antiviral combination therapy
      with ribavirin. All patients experienced some improvement of their cutaneous
      lesions, with two of them achieving complete MF remission. All six patients
      developed side effects while receiving treatment; two of them had grade 4 toxic
      effects requiring treatment discontinuation. CONCLUSION: IFN-based therapy can be
      administered for MF and HCV infection concurrently to provide not only
      virological but also oncological benefits to chronically HCV-infected MF
      patients. However, this regimen is poorly tolerated. Further studies are
      warranted in this patient population, using different treatment combinations with
      improved efficacy, safety, and tolerability.

PMID- 24934808
TI  - Selective and potent Akt inhibition triggers anti-myeloma activities and enhances
      fatal endoplasmic reticulum stress induced by proteasome inhibition.
AB  - The PI3K/Akt pathway plays a crucial role in the pathogenesis of multiple myeloma
      (MM) in the bone marrow (BM) milieu. However, efficacy of selective and potent
      Akt inhibition has not yet been fully elucidated. In this study, we, therefore,
      examined the biologic impact of selective and potent Akt inhibition by a novel
      allosteric inhibitor TAS-117. TAS-117 induced significant growth inhibition,
      associated with downregulation of phosphorylated Akt (p-Akt), selectively in MM
      cell lines with high baseline p-Akt. Cytotoxicity of TAS-117 was also observed in
      patient MM cells, but not in normal peripheral blood mononuclear cells.
      Importantly, TAS-117 induced significant cytotoxicity in MM cells even in the
      presence of BM stromal cells, associated with inhibition of IL6 secretion. Oral
      administration of TAS-117 significantly inhibited human MM cell growth in murine
      xenograft models. TAS-117 triggered apoptosis and autophagy, as well as induction
      of endoplasmic reticulum (ER) stress response with minimal expression of C/EBP
      homologous protein (CHOP), a fatal ER stress marker. Importantly, TAS-117
      enhanced bortezomib-induced cytotoxicity, associated with increased CHOP and PARP
      cleavage and blockade of bortezomib-induced p-Akt, suggesting that TAS-117
      augments bortezomib-induced ER stress and apoptotic signaling. Carfilzomib
      induced cytotoxicity was similarly enhanced by TAS-117. Importantly, TAS-117
      enhanced bortezomib-induced cytotoxicity in vivo, associated with prolonged host
      survival. Our results show that selective and potent Akt inhibition by TAS-117
      triggers anti-MM activities in vitro and in vivo, as well as enhances
      cytotoxicity of proteasome inhibition, providing the preclinical framework for
      clinical evaluation of selective Akt inhibitors, alone and in combination with
      proteasome inhibitors in MM.

PMID- 24934809
TI  - In vivo regulation of human glutathione transferase GSTP by chemopreventive
      agents.
AB  - Relatively little progress has been made in determining the in vivo regulation of
      glutathione S-transferase P (GSTP), particularly the human enzyme hGSTP1, despite
      being identified as a significant factor in carcinogenesis and development of
      drug resistance in tumor cell lines. Here, we report the characterization of a
      transgenic reporter mouse that reveals how hGSTP1 is regulated in vivo by
      chemopreventive agents. Basal expression was found in crypts and villi of the
      small and large intestine, bronchiolar epithelial cells, the epidermis and hair
      follicles, gall bladder epithelium, choroid plexus, and biliary epithelium.
      Expression was induced in different tissues by the antioxidant chemopreventive
      agents ethoxyquin and butylated hydroxyanisole. However, genetic deletion of the
      Nrf2 transcription factor, which directs central genetic programs of
      detoxification and protection against oxidative stress, increased rather than
      attenuated GSTP1 expression. In vitro investigations with mouse embryonic
      fibroblasts revealed factors, in addition to Nrf2, that control the expression of
      GSTP1, offering further insights into regulation. The new reporter mouse
      described here provides a useful tool to gain deeper insights into the mechanisms
      of action of chemopreventive compounds and other environmental agents.

PMID- 24934810
TI  - MYC synergizes with activated BRAFV600E in mouse lung tumor development by
      suppressing senescence.
AB  - The activated RAS/RAF cascade plays a crucial role in lung cancer, but is also
      known to induce cellular senescence, a major barrier imposed on tumor cells early
      in tumorigenesis. MYC is a key factor in suppression of RAS/BRAF(V600E)-induced
      senescence in vitro. However, it is still unclear whether MYC has the same role
      during tumor development in vivo. Using a conditional, compound knock-in model of
      Cre-activated BRAF(V600E) and tamoxifen-regulatable MycER, we show that tamoxifen
      induced activation of MYC accelerated the onset and increased the number and size
      of BRAF(V600E)-driven adenomas in a dose-dependent manner, resulting in reduced
      survival. Furthermore, MYC activation leads to reduced expression of the
      senescence markers p16(INK4A), p21(CIP1), and H3K9me3-containing heterochromatin
      foci, and an increased percentage of Ki67(+) tumor cells. This suggests that MYC
      already early during tumor formation suppresses a BRAF(V600E)-induced senescence
      like state. Initial activation of MYC followed by tamoxifen withdrawal still
      resulted in an increased number of tumors and reduced survival. However, these
      tumors were of smaller size, showed increased expression of p16(INK4A) and
      p21(CIP1), and reduced number of Ki67(+) cells, indicating that MYC inactivation
      restores BRAF(V600E)-induced senescence. Surprisingly, MYC activation did not
      promote adenoma to carcinoma progression. This suggests that senescence
      suppression by MYC is a discrete step in tumor development important for
      sustained tumor growth but preceding malignant transformation and that additional
      oncogenic events are required for carcinoma development and metastasis. These
      findings contribute to our understanding of the neoplastic transformation
      process, with implications for future treatment strategies.

PMID- 24934812
TI  - EWS-WT1 oncoprotein activates neuronal reprogramming factor ASCL1 and promotes
      neural differentiation.
AB  - The oncogenic fusion gene EWS-WT1 is the defining chromosomal translocation in
      desmoplastic small round-cell tumors (DSRCT), a rare but aggressive soft tissue
      sarcoma with a high rate of mortality. EWS-WT1 functions as an aberrant
      transcription factor that drives tumorigenesis, but the mechanistic basis for its
      pathogenic activity is not well understood. To address this question, we created
      a transgenic mouse strain that permits physiologic expression of EWS-WT1 under
      the native murine Ews promoter. EWS-WT1 expression led to a dramatic induction of
      many neuronal genes in embryonic fibroblasts and primary DSRCT, most notably the
      neural reprogramming factor ASCL1. Mechanistic analyses demonstrated that EWS-WT1
      directly bound the proximal promoter of ASCL1, activating its transcription
      through multiple WT1-responsive elements. Conversely, EWS-WT1 silencing in DSRCT
      cells reduced ASCL1 expression and cell viability. Notably, exposure of DSRCT
      cells to neuronal induction media increased neural gene expression and induced
      neurite-like projections, both of which were abrogated by silencing EWS-WT1.
      Taken together, our findings reveal that EWS-WT1 can activate neural gene
      expression and direct partial neural differentiation via ASCL1, suggesting agents
      that promote neural differentiation might offer a novel therapeutic approach to
      treat DSRCT.

PMID- 24934811
TI  - ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine
      signaling circuit.
AB  - The drug efflux transporter ABCB5 identifies cancer stem-like cells (CSC) in
      diverse human malignancies, where its expression is associated with clinical
      disease progression and tumor recurrence. ABCB5 confers therapeutic resistance,
      but other functions in tumorigenesis independent of drug efflux have not been
      described that might help explain why it is so broadly overexpressed in human
      cancer. Here we show that in melanoma-initiating cells, ABCB5 controls IL1beta
      secretion, which serves to maintain slow cycling, chemoresistant cells through an
      IL1beta/IL8/CXCR1 cytokine signaling circuit. This CSC maintenance circuit
      involved reciprocal paracrine interactions with ABCB5-negative cancer cell
      populations. ABCB5 blockade induced cellular differentiation, reversed resistance
      to multiple chemotherapeutic agents, and impaired tumor growth in vivo. Together,
      our results defined a novel function for ABCB5 in CSC maintenance and tumor
      growth.

PMID- 24934813
TI  - Candida colonization index and subsequent infection in critically ill surgical
      patients: 20 years later.
AB  - INTRODUCTION: For decades, clinicians dealing with immunocompromised and
      critically ill patients have perceived a link between Candida colonization and
      subsequent infection. However, the pathophysiological progression from
      colonization to infection was clearly established only through the formal
      description of the colonization index (CI) in critically ill patients.
      Unfortunately, the literature reflects intense confusion about the
      pathophysiology of invasive candidiasis and specific associated risk factors.
      METHODS: We review the contribution of the CI in the field of Candida infection
      and its development in the 20 years following its original description in 1994.
      The development of the CI enabled an improved understanding of the pathogenesis
      of invasive candidiasis and the use of targeted empirical antifungal therapy in
      subgroups of patients at increased risk for infection. RESULTS: The recognition
      of specific characteristics among underlying conditions, such as neutropenia,
      solid organ transplantation, and surgical and nonsurgical critical illness, has
      enabled the description of distinct epidemiological patterns in the development
      of invasive candidiasis. CONCLUSIONS: Despite its limited bedside practicality
      and before confirmation of potentially more accurate predictors, such as specific
      biomarkers, the CI remains an important way to characterize the dynamics of
      colonization, which increases early in patients who develop invasive candidiasis.

PMID- 24934815
TI  - Taichi exercise for self-rated sleep quality in older people: a systematic review
      and meta-analysis.
AB  - OBJECTIVES: Self-reported sleep disorders are common in older adults, resulting
      in serious consequences. Non-pharmacological measures are important complementary
      interventions, among which Taichi exercise is a popular alternative. Some
      experiments have been performed; however, the effect of Taichi exercise in
      improving sleep quality in older people has yet to be validated by systematic
      review. Using systematic review and meta-analysis, this study aimed to examine
      the efficacy of Taichi exercise in promoting self-reported sleep quality in older
      adults. DESIGN: Systematic review and meta-analysis of randomized controlled
      studies. DATA SOURCES: 4 English databases: Pubmed, Cochrane Library, Web of
      Science and CINAHL, and 4 Chinese databases: CBMdisc, CNKI, VIP, and Wanfang
      database were searched through December 2013. REVIEW METHODS: Two reviewers
      independently selected eligible trials, conducted critical appraisal of the
      methodological quality by using the quality appraisal criteria for randomized
      controlled studies recommended by Cochrane Handbook. A standardized data form was
      used to extract information. Meta-analysis was performed. RESULTS: Five
      randomized controlled studies met inclusion criteria. All suffered from some
      methodological flaws. The results of this study showed that Taichi has large
      beneficial effect on sleep quality in older people, as indicated by decreases in
      the global Pittsburgh Sleep Quality Index score [standardized mean difference=
      0.87, 95% confidence intervals (95% confidence interval) (-1.25, -0.49)], as well
      as its sub-domains of subjective sleep quality [standardized mean difference=
      0.83, 95% confidence interval (-1.08, -0.57)], sleep latency [standardized mean
      difference=-0.75, 95% confidence interval (-1.42, -0.07)], sleep duration
      [standardized mean difference=-0.55, 95% confidence interval (-0.90, -0.21)],
      habitual sleep efficiency [standardized mean difference=-0.49, 95% confidence
      interval (-0.74, -0.23)], sleep disturbance [standardized mean difference=-0.44,
      95% confidence interval (-0.69, -0.19)], and daytime dysfunction [standardized
      mean difference=-0.34, 95% confidence interval (-0.59, -0.09)]. Daytime
      sleepiness improvement was also observed. CONCLUSIONS: Weak evidence shows that
      Taichi exercise has a beneficial effect in improving self-rated sleep quality for
      older adults, suggesting that Taichi could be an effective alternative and
      complementary approach to existing therapies for older people with sleep
      problems. More rigorous experimental studies are required.

PMID- 24934814
TI  - Impact of fluid balance on outcome of adult patients treated with extracorporeal
      membrane oxygenation.
AB  - PURPOSE: To assess the relationship between early daily fluid balance (FB) and 90
      day outcome in adult patients treated with extracorporeal membrane oxygenation
      (ECMO). DESIGN: Retrospective observational study. SETTING: Tertiary referral
      centre for ECMO. PATIENTS: 115 patients treated with ECMO for refractory heart
      failure and 57 patients treated with ECMO for refractory respiratory failure.
      METHODS: We analysed the association between early daily FB versus hospital and
      90-day mortality using multivariable logistic regression model, Cox proportional
      hazards model and propensity score. RESULTS: We obtained detailed demographic,
      clinical, and biochemical data, daily FB, and continuous renal replacement days.
      Fifty-seven per cent of patients had acute kidney injury (AKI) at ECMO
      initiation, and 60 % (n = 103) of patients received continuous renal replacement
      therapy (CRRT) during ECMO course, beginning at a median of 1 (0-3.5) days after
      ECMO initiation. Overall 90-day mortality was 24 %. Survivors exhibited lower
      daily FB from day 3 to day 5. After adjustments, Acute Physiology and Chronic
      Health Evaluation (APACHE) III, CRRT during the first 3 days, major bleeding
      event at day 1 and positive FB on day 3 were independent predictors of 90-day
      mortality. Positive FB at ECMO day 3 remained an independent predictor of
      hospital and 90-day mortality, regardless of the statistical model used or the
      inclusion of a propensity score to have positive FB. CONCLUSIONS: Positive FB at
      ECMO day 3 is an independent predictor of 90-day mortality. Further
      interventional studies aimed at testing the value of strategy of tight control of
      FB during the early ECMO period are now warranted.

PMID- 24934819
TI  - Pressure-induced structural changes and insulator-metal transition in layered
      bismuth triiodide, BiI3: a combined experimental and theoretical study.
AB  - Noting that BiI3 and the well-known topological insulator (TI) Bi2Se3 have the
      same high symmetry parent structures, and that it is desirable to find a wide
      band gap TI, we determine here the effects of pressure on the structure, phonons
      and electronic properties of rhombohedral BiI3. We report a pressure-induced
      insulator-metal transition near 1.5 GPa, using high pressure electrical
      resistivity and Raman measurements. X-ray diffraction studies, as a function of
      pressure, reveal a structural peculiarity of the BiI3 crystal, with a drastic
      drop in c/a ratio at 1.5 GPa, and a structural phase transition from rhombohedral
      to monoclinic structure at 8.8 GPa. Interestingly, the metallic phase, at
      relatively low pressures, exhibits minimal resistivity at low temperatures,
      similar to that in Bi2Se3. We corroborate these findings with first-principles
      calculations and suggest that the drop in the resistivity of BiI3 in the 1-3 GPa
      range of pressure arises possibly from the appearance of an intermediate crystal
      phase with a lower band-gap and hexagonal crystal structure. Calculated Born
      effective charges reveal the presence of metallic states in the structural
      vicinity of rhombohedral BiI3. Changes in the topology of the electronic bands of
      BiI3 with pressure, and a sharp decrease in the c/a ratio below 2 GPa, are shown
      to give rise to changes in the slope of phonon frequencies near that pressure. 

PMID- 24934816
TI  - Anthropometric and lifestyle characteristics of active and inactive Saudi and
      British adolescents.
AB  - OBJECTIVES: To compare the anthropometric and lifestyle characteristics of active
      and inactive adolescents in Saudi Arabia and Britain. METHODS: A school-based
      cross-sectional study was conducted at four cities in Saudi Arabia (Riyadh and Al
      Khobar; N = 1,648) and Britain (Birmingham and Coventry; N = 1,158). The
      participants (14- to 18-year-olds) were randomly selected using a multistage
      stratified cluster sampling. Measurements included anthropometric [BMI, Waist
      circumference (WC), Waist to height ratio], screen time, validated physical
      activity questionnaire and dietary habits. RESULTS: British males were lighter (P
      = 0.04, 64.4 vs. 68.2 kg), and had lower values for WC (P = 0.003, 77.1 vs. 78.7
      cm) than Saudi males. Males (P = 0.0001) were significantly more active than
      females but the difference between inactive Saudi and British females was greater
      than that between inactive Saudi and British males. Being female was
      significantly (P < 0.001) associated with lower activity levels in both the Saudi
      and British adolescents. Having lower frequency of fruit intake was significantly
      (P < 0.001) associated with lower activity levels, whereas increased frequency of
      consumption of French fries/potato chips was significantly (P = 0.008) associated
      with increased activity levels in Saudi adolescents. Among British adolescents,
      lower frequency of breakfast was (P = 0.045) associated with lower activity
      levels, increased frequency of consumption of sweetened beverages was
      significantly (P = 0.005) associated with higher activity levels. Higher energy
      drinks intake frequency was significantly (P = 0.007) associated with higher
      activity levels. CONCLUSION: The present study identifies crosscultural
      differences and similarities in lifestyle habits in adolescents from Britain and
      Saudi Arabia. Activity status (active vs. inactive) appears to play an important
      role in other lifestyle related behaviors, with active adolescent more likely to
      engage in healthy dietary behavior than their inactive peers, irrespective of
      country of origin.

PMID- 24934820
TI  - [Fixed pigmented erythema antihistamine H1: about 2 cases and review of the
      literature].
AB  - We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case)
      and loratadine (2(nd) case). 

PMID- 24934822
TI  - [Methandienone misuse: interest of medical anti-doping units].
AB  - We report a case of methandienone misuse leading to a preventive action of the
      Lorraine medicale anti-doping unit. 

PMID- 24934821
TI  - Facial hyperpigmentation during imatinib therapy for gastrointestinal stromal
      tumor.
AB  - We report a rare case of facial hyperpigmentation during imatinib therapy for a
      gastrointestinal stromal tumor. 

PMID- 24934823
TI  - Valvular heart disease associated with long-term treatment by methysergide: a
      case report.
AB  - This case report concerns a woman treated continuously since at least 10 years by
      methysergide for cluster headache. The echocardiographic and histological
      features of the severe valve fibrosis presented by this patient are very similar
      to those described with 5 HT(2B) receptors agonistic drugs.

PMID- 24934824
TI  - Primary epiploic appendagitis: reconciling CT and clinical challenges.
AB  - OBJECTIVES: Our aim was to explain the spectrum of clinical and CT findings in 18
      patients with acute epiploic appendagitis. METHODS AND MATERIALS: We reviewed the
      clinical records and CT pictures of 18 consecutive patients seen in Nejran Armed
      Forces Hospital, Nejran, Kingdom of Saudi Arabia and Sohag University Hospital,
      Sohag, Egypt between July 2006 and June 2013 with a diagnosis of primary epiploic
      appendagitis. RESULTS: The age ranged between 22 and 64 years old with a mean of
      44.3. Males were affected in 72 % of cases. Eleven patients had acute pain in
      left lower quadrant. Nausea and vomiting were encountered in four patients. No
      fever was recorded in all cases. Leukocytosis was found in four patients and C
      reactive protein (CRP) was high in five. CT scan diagnosed primary epiploic
      appendagitis (PEA) in 15 patients, while 3 patients were diagnosed
      intraoperatively. The left colon was affected in 11 patients. All patients except
      one had a central fatty core surrounded by inflammation with size ranging between
      1.5 and 3.5 cm in length. Fifteen patients were treated conservatively, and three
      cases underwent surgical exploration. Ten patients (55.5 %) completed the follow
      up schedule. Complete resolution was noted in three patients at 2 weeks, in six
      patients at 3 months, and only one patient had residual changes at 6 months.
      CONCLUSION: PEA is a challenging clinical diagnosis, and CT scan is extremely
      necessary in diagnosing this disease accurately. The awareness of the surgeons
      concerning this rare occasion will avoid unnecessary hospital admission and
      operative treatment.

PMID- 24934825
TI  - D-Xylose assimilation via the Weimberg pathway by solvent-tolerant Pseudomonas
      taiwanensis VLB120.
AB  - The natural ability of Pseudomonas taiwanensis VLB120 to use xylose as sole
      carbon and energy source offers a high potential for sustainable industrial
      biotechnology. In general, three xylose assimilation routes are reported for
      bacteria. To elaborate the metabolic capacity of P. taiwanensis VLB120 and to
      identify potential targets for metabolic engineering, an in silico/in vivo
      experiment was designed, allowing for discrimination between these pathways.
      Kinetics of glucose and xylose degradation in P. taiwanensis VLB120 was
      determined and the underlying stoichiometry was investigated by genome-based
      metabolic modelling and tracer studies using stable isotope labelling.
      Additionally, reverse transcription quantitative polymerase chain reaction
      experiments have been performed to link physiology to the genomic inventory.
      Based on in silico experiments, a labelling strategy was developed, ensuring a
      measurable and unique (13) C-labelling distribution in proteinogenic amino acids
      for every possible distribution between the different xylose metabolization
      routes. A comparison with in vivo results allows the conclusion that xylose is
      metabolized by P. taiwanensis VLB120 via the Weimberg pathway. Transcriptomic and
      physiological studies point to the biotransformation of xylose to xylonate by
      glucose dehydrogenase. The kinetics of this enzyme is also responsible for the
      preference of glucose as carbon source by cells growing in the presence of
      glucose and xylose. 

PMID- 24934826
TI  - Acting in the face of uncertainty.

PMID- 24934827
TI  - Thyroid function and dysfunction in term and premature equine neonates.
AB  - BACKGROUND: This study was performed to compare thyroid function of premature
      foals to term foals. HYPOTHESIS: Premature foals are more markedly
      hypothyroxinemic than expected for their severity of illness alone. ANIMALS:
      Twenty clinically normal term foals; 28 sick, hospitalized term foals; 24 sick,
      hospitalized premature foals. METHODS: Thyroid hormones (TH) and thyrotropin
      (TSH) were measured, both at rest and in response to thyrotropin-releasing
      hormone (TRH), in the 3 groups of foals. Clinical and clinicopathologic data were
      recorded. RESULTS: Normal foals had high TH at birth, which decreased over the
      first month into the normal reference range for adult horses. TSH was within the
      normal adult reference range soon after birth, and did not change over time. At
      24-36 hours of age, triiodothyronine (T3) was significantly lower in both
      premature and term hospitalized foals compared to normal foals; premature foals
      were not different from term hospitalized foals. Thyroxine (T4) was not different
      between normal and term hospitalized foals, but was significantly lower than in
      premature foals of both of these groups. TSH was not different among the 3
      groups. TRH stimulation tests identified significant differences in T4 among all
      3 groups of foals, whereas T3 was similar in premature and term hospitalized
      foals and different from normal foals. TSH response to TRH was significantly
      higher in premature foals compared to normal foals. CONCLUSIONS AND CLINICAL
      IMPORTANCE: The hypothalamic-pituitary-thyroid axis is different in foals
      compared to adult horses. Sick foals exhibit nonthyroidal illness syndrome.
      Premature foals are more markedly hypothyroxinemic than can be accounted for by
      their severity of illness alone.

PMID- 24934828
TI  - Describing drivers of and barriers to persistence with tiotropium in patients
      with chronic obstructive pulmonary disease: a mixed-methods approach.
AB  - OBJECTIVE: To understand the factors influencing persistence with tiotropium in
      patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients
      classified as 'persistent' or 'non-persistent' with tiotropium were identified
      from pharmacy dispensing records. Patients were compared for health status,
      beliefs and behaviours using data from questionnaires and interviews. KEY
      FINDINGS: Perceptions of the risks and benefits of medication, fear of worsening
      illness, and the GP's emphasis on the importance of the medication were key
      determinants of tiotropium persistence. CONCLUSIONS: Perceptions, attitudes and
      beliefs of patients and doctors influence persistence with tiotropium. These
      complex interactions need to be targeted to improve persistence with medicines in
      COPD.

PMID- 24934829
TI  - Preparation of stimuli-responsive "mushroom-like" janus polymer particles as
      particulate surfactant by site-selective surface-initiated AGET ATRP in aqueous
      dispersed systems.
AB  - Micrometer-sized, monodisperse, "mushroom-like" Janus poly(methyl
      methacrylate)/poly(styrene-2-(2-bromoisobutyryloxy)ethyl methacrylate)-graft
      poly(2-(dimethyl amino)ethyl methacrylate) (PMMA/P(S-BIEM)-g-PDM) particles were
      successfully synthesized by site-selective surface-initiated activator generated
      by electron transfer for atom transfer radical polymerization in aqueous
      dispersed systems with spherical PMMA/P(S-BIEM) composite particles having
      controlled morphologies prepared using the solvent evaporation method. The
      anisotropic nonspherical shape of the obtained particles was controlled by
      changing the percentage of the surface area occupied by localized initiation
      sites (bromine group) at the surface of the PMMA/P(S-BIEM) composite particles
      with different P(S-BIEM) contents. Grafted PDM layer formed at the surface
      (contacting with water) of the P(S-BIEM) phase reversibly exhibited the volume
      phase transition in response to temperature and pH, which gave different
      nonspherical shapes ("open" or "closed" mushroom-cap). On the basis of such dual
      stimuli-responsive properties, the nonspherical particles effectively operated as
      particulate surfactant for Pickering emulsion, resulting in a stable 1-octanol-in
      water emulsion at optimum temperature and pH value, and the Pickering emulsion
      could be easily unstabilized quickly by controlling them. 

PMID- 24934830
TI  - A profile of travelers--an analysis from a large swiss travel clinic.
AB  - BACKGROUND: Globally, the Swiss have one of the highest proportions of the
      population traveling to tropical and subtropical countries. Large travel clinics
      serve an increasing number of customers with specific pre-travel needs including
      uncommon destinations and preexisting medical conditions. This study aims to
      identify health characteristics and travel patterns of travelers seeking advice
      in the largest Swiss travel clinic so that tailored advice can be delivered.
      METHODS: A descriptive analysis was performed on pre-travel visits between July
      2010 and August 2012 at the Travel Clinic of the Institute of Social and
      Preventive Medicine, University of Zurich, Switzerland. RESULTS: A total of
      22,584 travelers sought pre-travel advice. Tourism was the main reason for travel
      (17,875, 81.5%), followed by visiting friends and relatives (VFRs; 1,715, 7.8%),
      traveling for business (1,223, 5.6%), and "other reasons" (ie, volunteer work,
      pilgrimage, study abroad, and emigration; 1,112, 5.1%). The main travel
      destination was Thailand. In the VFR group, the highest proportions of traveling
      children (258, 15.1%) and of pregnant or breastfeeding women (23, 3.9%) were
      observed. Mental disorders were more prominent in VFRs (93, 5.4%) and in travel
      for "other reasons" (63, 5.7%). The latter stayed for the longest periods abroad;
      272 (24.9%) stayed longer than 6 months. VFR travelers received the highest
      percentage of yellow fever vaccinations (523, 30.5%); in contrast, rabies (269,
      24.2%) and typhoid vaccinations (279, 25.1%) were given more often to the "other
      travel reasons" group. CONCLUSIONS: New insights into the characteristics of a
      selected and large population of Swiss international travelers results in
      improved understanding of the special needs of an increasingly diverse population
      and, thus, in targeted preventive advice and interventions.

PMID- 24934833
TI  - Predicting admission of patients by their presentation to the emergency
      department.
AB  - OBJECTIVE: The present study aims to determine the importance of certain factors
      in predicting the need of hospital admission for a patient in the ED. METHODS:
      This is a retrospective observational cohort study between January 2010 and March
      2012. The characteristics, including blood test results, of 100,123 patients who
      presented to the ED of a tertiary referral urban hospital, were incorporated into
      models using logistic regression in an attempt to predict the likelihood of
      patients' disposition on leaving the ED. These models were compared with triage
      nurses' prediction of patient disposition. RESULTS: Patient age, their initial
      presenting symptoms or diagnosis, Australasian Triage Scale category, mode of
      arrival, existence of any outside referral, triage time of day and day of the
      week were significant predictors of the patient's disposition (P < 0.001). The
      ordering of blood tests for any patient and the extent of abnormality of those
      tests increased the likelihood of admission. The accuracy of triage nurses'
      admission prediction was similar to that offered by a model that used the
      patients' presentation characteristics. The addition of blood tests to that model
      resulted in only 3% greater accuracy in prediction of patient disposition.
      CONCLUSIONS: Certain characteristics of patients as they present to hospital
      predict their admission. The accuracy of the triage nurses' prediction for
      disposition of patients is the same as that afforded by a model constructed from
      these characteristics. Blood test results improve disposition accuracy only
      slightly so admission decisions should not always wait for these results.

PMID- 24934832
TI  - Dynamics of allograft fibrosis in pediatric liver transplantation.
AB  - Progressive liver allograft fibrosis (LAF) is well known to occur long term, as
      shown by its high prevalence in late posttransplant liver biopsies (LBs). To
      evaluate the influence of clinical variables and immunosuppression on LAF
      progression, LAF dynamic was assessed in 54 pediatric liver transplantation (LT)
      recipients at 6 months, 3 and 7 years post-LT, reviewing clinical, biochemical
      data and protocol LBs using METAVIR and the liver allograft fibrosis score,
      previously designed and validated specifically for LAF assessment. Scoring
      evaluations were correlated with fibrosis quantification by morphometric
      analysis. Progressive LAF was found in 74% of long-term patients, 70% of whom had
      unaltered liver enzymes. Deceased grafts showed more fibrosis than living-related
      grafts (p = 0.0001). Portal fibrosis was observed in correlation with prolonged
      ischemia time, deceased grafts and lymphoproliferative disease (p = 0.001, 0.006
      and 0.012, respectively). Sinusoidal fibrosis was correlated with biliary
      complications (p = 0.01). Centrilobular fibrosis was associated with vascular
      complications (p = 0.044), positive autoantibodies (p = 0.017) and high gamma
      globulins levels (p = 0.028). Steroid therapy was not associated with reduced
      fibrosis (p = 0.83). LAF could be viewed as a dynamic process with mostly
      progression along the time. Peri- and post-LT-associated factors may condition
      fibrosis development in a specific area of the liver parenchyma. 

PMID- 24934831
TI  - Next generation modeling in GWAS: comparing different genetic architectures.
AB  - The continuous advancement in genotyping technology has not been accompanied by
      the application of innovative statistical methods, such as multi-marker methods
      (MMM), to unravel genetic associations with complex traits. Although the
      performance of MMM has been widely explored in a prediction context, little is
      known on their behavior in the quantitative trait loci (QTL) detection under
      complex genetic architectures. We shed light on this still open question by
      applying Bayes A (BA) and Bayesian LASSO (BL) to simulated and real data. Both
      methods were compared to the single marker regression (SMR). Simulated data were
      generated in the context of six scenarios differing on effect size, minor allele
      frequency (MAF) and linkage disequilibrium (LD) between QTLs. These were based on
      real SNP genotypes in chromosome 21 from the Spanish Bladder Cancer Study. We
      show how the genetic architecture dramatically affects the behavior of the
      methods in terms of power, type I error and accuracy of estimates. Markers with
      high MAF are easier to detect by all methods, especially if they have a large
      effect on the phenotypic trait. A high LD between QTLs with either large or small
      effects differently affects the power of the methods: it impairs QTL detection
      with BA, irrespectively of the effect size, although boosts that of small effects
      with BL and SMR. We demonstrate the convenience of applying MMM rather than SMR
      because of their larger power and smaller type I error. Results from real data
      when applying MMM suggest novel associations not detected by SMR. 

PMID- 24934834
TI  - Increasing incidence of bullous pemphigoid in Northern Finland: a retrospective
      database study in Oulu University Hospital.
AB  - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disease of
      elderly people. Some studies have suggested that the incidence of BP has
      increased, but the diagnostic accuracy and methodology of studies have varied
      considerably. OBJECTIVES: To examine the incidence of BP in Northern Finland, and
      whether the incidence has changed over time. METHODS: This was a retrospective
      database study of all BP cases diagnosed in the Oulu University Hospital, Finland
      between 1985 and 2009. The diagnostic criteria were clinical features
      characteristic of BP (all patients) and positive direct or indirect
      immunofluorescence in the skin biopsy. The age-standardized incidences were
      calculated by the direct standardization method. Incidence rate ratios (IRR) were
      estimated by the Poisson regression model. To derive adjusted IRRs, age and sex
      were used as potential confounding factors. RESULTS: The crude incidence of BP
      was 17 per 1 million person-years [95% confidence interval (CI) 15-20] between
      1985 and 2009. Using the general European population as a reference, the age
      standardized incidence was 14 per 1 million person-years (95% CI 12-17). The
      incidence of BP increased 1.8-fold (IRR 1.8, 95% CI 1.3-2.6; P < 0.001) in 2005
      09 compared with the mean incidence of BP between 1985 and 2004, but after the
      adjustment for age and sex the increase was 1.4-fold (IRR 1.4, 95% CI 1.0-2.0; P
      = 0.043). CONCLUSIONS: This is the first study with immunohistologically verified
      BP diagnoses that reports the increase in the incidence of BP in age- and sex
      adjusted populations.

PMID- 24934835
TI  - Editor's Letter.

PMID- 24934836
TI  - Risk, Feasibility, and Cost Evaluation of a Prisoner Condom Access Pilot Program
      in One California State Prison.
AB  - This study evaluated the safety and security impact, feasibility, and cost of a
      program to provide condoms to inmates. A 1-year pilot study of wall-mounted
      condom dispensing machines in one California state prison compared pre- and post
      intervention rates of penal code violations related to sexual misconduct,
      contraband, controlled substances, and violence. The rates of penal code
      violations were unchanged or decreased compared to the pre-pilot year. Discreetly
      located condom dispensers were vandalized less frequently than those in plain
      view (p < .05). Distributing condoms using the pilot model would cost less than
      $2 per inmate annually. Results suggest that the use of discreetly located
      dispensing machines is an acceptable, feasible, low-cost option to prevent the
      transmission of sexually transmitted diseases and poses no safety or security
      risk in a typical medium-security prison setting.

PMID- 24934838
TI  - The Impact of Traumatic Brain Injury on Prison Health Services and Offender
      Management.
AB  - A large percentage of incarcerated offenders report a history of traumatic brain
      injury (TBI) with concomitant neuropsychiatric and social sequelae. However,
      research looking at the relationship between TBI and delivery of correctional
      health services and offender management is limited. In this study, the
      relationships between TBI and use of correctional medical/psychological services,
      chemical dependency (CD) treatment completion rates, in-prison rule infractions,
      and recidivism were investigated. Findings indicated that TBI history has a
      statistically significant association with increased usage of correctional
      medical/psychological services, including crisis interventions services, and with
      higher recidivism rates. Results also showed a trend toward offenders with TBI
      incurring higher rates of in-prison rule infractions and lower rates of CD
      treatment completion. Implications and future directions for correctional systems
      are discussed.

PMID- 24934837
TI  - A Condom Distribution Program in the Los Angeles Men's Central Jail: Sheriff
      Deputies' Attitudes and Opinions.
AB  - The K6G unit of Los Angeles Men's Central Jail is comprised of males who have sex
      with males (MSM), whether gay, bisexual, or transgender. Within this unit,
      condoms are distributed to inmates, one condom per week. The current study was
      conducted to better understand the experiences and opinions of jail staff as they
      pertain to the condom distribution program's effectiveness and impact on jail
      safety and management. A total of 10 staff interviews were conducted with the
      unit's line staff (n = 8) and administrative personnel (n = 2). Findings suggest
      that despite the contradictory "mixed message" that jail staff felt the program
      sent, it causes few operational or safety concerns and is perceived to be
      beneficial to public health.

PMID- 24934839
TI  - Measuring HIV Knowledge Among Women Incarcerated in Jail.
AB  - Incarcerated women often have arresting behaviors that are also high risk for
      acquiring HIV, such as drug use and sex work. Little research has been done
      related to HIV knowledge among women in jail. This study assessed HIV knowledge
      among English-speaking women 18 years and older detained in a large, Southeastern
      jail (N = 202). HIV knowledge was assessed using the Brief HIV Knowledge
      Questionnaire. HIV knowledge scores were significantly lower among women over age
      50, F(3, 195) = 7.39, p < .001; those with less than a high school education,
      F(2, 187) = 4.10, p = .018; and those with no history of sexually transmitted
      infections, F(1, 200) = 7.66, p = .006. Assessment of HIV knowledge among
      incarcerated women revealed a need for prevention education.

PMID- 24934840
TI  - Evaluation of a Renal Transplant Program for Incarcerated ESRD Patients.
AB  - Renal transplantation (Tx) improves mortality and morbidity but is limited by
      availability of suitable organs. Clinical and economic impact of a Tx program for
      end-stage renal disease (ESRD) prisoners was evaluated. Wait list time and
      patient and organ survival rates were assessed. Twelve of the 104 ESRD prisoners
      at a prison dialysis unit were activated; 9 transplanted, 2 released active on
      the United Network for Organ Sharing list, and 1 died after listing. Kidneys from
      antibody-positive hepatitis C (HepC) donors were given to consenting HepC
      antibody-positive recipients. The average waiting period was 6.6 months for HepC
      positive kidney recipients and 49.6 months for others. Compared with costs of
      continuing dialysis, Tx resulted in substantial savings. Patients with HepC
      experienced good graft and survival rates when given grafts from HepC donors,
      suggesting that transplantation is a viable, cost-effective option for the
      incarcerated patient with ESRD including those who have chronic HepC infection.

PMID- 24934841
TI  - Distribution of A(H1N1)pdm09 Influenza Vaccine: Need for Greater Consideration of
      Smaller Jails.
AB  - To identify factors associated with vaccine receipt among correctional facilities
      during the A(H1N1)pdm09 influenza pandemic, this study surveyed one third of U.S.
      correctional facilities. Analysis of the association of average daily population
      (ADP) on A(H1N1)pdm09 influenza vaccine receipt found that an ADP increase of 100
      inmates resulted in a 32% increased likelihood of receiving influenza vaccine
      among smaller jails. Zero percent of large jails, 14% of federal prisons, 11% of
      nonfederal prisons, and 57% of small jails reported never receiving pandemic
      influenza vaccine. A qualitative assessment identified barriers to vaccine
      delivery, lessons learned from pandemic response, and recommendations for public
      health partners. Building stronger relationships between public health entities
      and correctional facilities to collaborate in influenza pandemic preparedness
      efforts may help protect correctional and community populations.

PMID- 24934842
TI  - Simulation: Introduction to Correctional Nursing in a Prison Setting.
AB  - Simulation can be used to introduce students to critical nursing skills that
      reduce errors, enhance nurse-patient communication, and improve safety and
      security when caring for patients in the correctional setting. The interactive
      environment creates scenarios in a realistic fashion that include experiences
      that nursing students may encounter in a correctional facility setting, such as
      aggressive clients, gang-related activities, and noncompliant personalities.
      Orientation prior to entering the facilities is the key to safety, reducing
      student anxiety, and enhancing the student's ability to learn. The simulation
      scenario designed for the correctional setting provides an environment for the
      teaching and learning of correctional nursing skills and multidisciplinary
      collaboration. Scenarios are embedded with communication, safety, delegation, and
      critical thinking education goals. Student evaluations are assessed and reported.

PMID- 24934843
TI  - Psychoactive Medication Misadventuring in Correctional Health Care.
AB  - Due to multiple factors, unprecedented numbers of individuals with mental health
      disorders and many with comorbid substance use disorders are now incarcerated in
      jails and prisons. This article details a variety of medication use and potential
      abuse/misuse/misadventuring topics that are unique to the correctional health
      care setting, with emphasis on how the large number of persons with psychiatric
      and/or substance use disorders affects these issues and methods that correctional
      systems commonly use to manage these inmate-patients. Also discussed are the
      potential for inmate feigning or malingering as a goal-directed behavior,
      potential for misadventuring/abuse of commonly used medications, urine drug
      screening/surveillance, and the effect of psychoactive medications on heat
      tolerance and environmental issues.

PMID- 24934844
TI  - Journal of Correctional Health Care.

PMID- 24934846
TI  - Safety in childbirth: can India maintain its momentum?

PMID- 24934845
TI  - Comparative effectiveness of a multifaceted intervention to improve adherence to
      annual colorectal cancer screening in community health centers: a randomized
      clinical trial.
AB  - IMPORTANCE: Colorectal cancer (CRC) screening rates are lower among Latinos and
      people living in poverty. Fecal occult blood testing (FOBT) is one recommended
      screening modality that may overcome cost and access barriers. However, the
      ability of FOBT to reduce CRC mortality depends on high rates of adherence to
      annual screening. OBJECTIVE: To determine whether a multifaceted intervention
      increases adherence to annual FOBT compared with usual care. DESIGN, SETTING, AND
      PARTICIPANTS: Patient-level randomized controlled trial conducted in a network of
      community health centers. Included were 450 patients who had previously completed
      a home FOBT from March 2011 through February 2012 and had a negative test result:
      72% of participants were women; 87% were Latino; 83% stated that Spanish was
      their preferred language; and 77% were uninsured. INTERVENTIONS: Usual care at
      participating health centers included computerized reminders, standing orders for
      medical assistants to give patients home fecal immunochemical tests (FIT), and
      clinician feedback on CRC screening rates. The intervention group also received
      (1) a mailed reminder letter, a free FIT with low-literacy instructions, and a
      postage-paid return envelope; (2) an automated telephone and text message
      reminding them that they were due for screening and that a FIT was being mailed
      to them; (3) an automated telephone and text reminder 2 weeks later for those who
      did not return the FIT; and (4) personal telephone outreach by a CRC screening
      navigator after 3 months. MAIN OUTCOMES AND MEASURES: Completion of FOBT within 6
      months of the date the patient was due for annual screening. RESULTS:
      Intervention patients were much more likely than those in usual care to complete
      FOBT (82.2% vs 37.3%; P < .001). Of the 185 intervention patients completing
      screening, 10.2% completed prior to their due date (intervention was not given),
      39.6% within 2 weeks (after initial intervention), 24.0% within 2 to 13 weeks
      (after automated call/text reminder), and 8.4% between 13 and 26 weeks (after
      personal call). CONCLUSIONS AND RELEVANCE: This intervention greatly increased
      adherence to annual CRC screening; most screenings were achieved without personal
      calls. It is possible to improve annual CRC screening for vulnerable populations
      with relatively low-cost strategies that are facilitated by health information
      technologies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01453894.

PMID- 24934847
TI  - Chemoimmunotherapy with oral low-dose fludarabine, cyclophosphamide and rituximab
      (old-FCR) as treatment for elderly patients with chronic lymphocytic leukaemia.
AB  - Median age at diagnosis for chronic lymphocytic leukaemia (CLL) patients is now
      72 years, thus a consistent number of patients may not tolerate standard doses
      i.v. of fludarabine, cyclophosphamide and rituximab (FCR), the best available
      therapy, due to unacceptable myelotoxicity and risk of severe infections. We
      studied safety and efficacy of the addition of rituximab to the oral low-dose FC
      regimen (old-FCR) in a selected population of 30 elderly (median age 75, 15
      untreated, 15 treated with 1 prior therapy) CLL patients. Complete remission (CR)
      rate was 80% in the untreated patients (overall response rate, ORR 93%), and 30%
      in pretreated patients (ORR 74%). Progression free survivals (PFS) were 45 months
      and 30 months in the untreated and treated patients, respectively. In patients
      achieving CR, old-FCR led to PFS of 67 months. Moreover, haematological toxicity
      was mild (grade 3-4: 15%) and patients were treated mostly in outpatient clinic.
      Old-FCR could be a good therapy option for elderly CLL patients outside clinical
      trials, larger studies are needed to confirm our findings. 

PMID- 24934848
TI  - Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven
      hematological cancers.
AB  - In order to stimulate antigen presentation and T cell activity against cancer, we
      treated three different tumor models in mice with the monoclonal antibodies anti
      CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer
      model, there was significant enhancement in the survival of mice following BiMab
      treatment. Anti-CD40 has shown considerable success against lymphoma in previous
      studies by other investigators, and we also showed in this study that, in a model
      of EMU-Myc lymphoma, there was a statistically significant enhancement of
      survival of mice following BiMab treatment. Following the success of the BiMab
      treatment in the previous two models, we wished to determine if it would be
      successful in a mouse model of multiple myeloma. Firstly, we tested a
      transplantable model of disease in which multiple myeloma cells derived from
      Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and
      BiMab treated mice experienced prolongation of life beyond 250 days. Then we
      tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC
      transgenic mice. The majority of mice treated survived longer than control mice,
      although statistical significance was not demonstrated. 

PMID- 24934850
TI  - Oxygenated fatty acids isolated from wheat bran slurries.
AB  - Oxygenated fatty acids are classified as secondary metabolites in wheat, produced
      by oxidation of free fatty acids (FFAs). Oxygenated fatty acids have significant
      impact on the organoleptic and sensory properties of food products and
      participate in regulation of defense and developmental processes in plants. The
      objective of this study was to identify oxygenated fatty acids from wheat flour
      slurries. Wheat bran/water slurries were incubated for 4 h and freeze dried.
      Total lipids were extracted in chloroform/methanol/water; and methylated and
      silylated FFAs were analyzed with gas chromatography/mass spectroscopy. Seven
      oxygenated fatty acids were identified, (A) 12,13-dihydroxy-9-octadecenoic acid,
      (B) 9-hydroxy-10,12-octadecadienoic acid, (C) 13-hydroxy-9cis,11trans
      octadecadienoic acid, (D) 9,10,13-trihydroxy-11trans-octadecenoic acid, (E)
      9,12,13-trihydroxy-10trans,15cis-octadecadienoic acid, (F) 10-oxo-13-hydroxy
      11trans-octadecenoic acid and (G) 12-oxo-13-hydroxy-octadecanoic acid, in wheat
      bran slurries. Our results are important for whole wheat food applications since
      oxygenated fatty acids can result in bitter flavors in the final product.

PMID- 24934849
TI  - Malaria chemoprophylaxis regimens: a descriptive drug utilization study.
AB  - BACKGROUND: Mefloquine belongs to the priority chemoprophylaxis drugs for
      travelers to malaria endemic regions. We aimed to assess the prescribing patterns
      for mefloquine and other antimalarials. METHODS: We conducted a descriptive drug
      utilization study using the U.K. Clinical Practice Research Datalink (CPRD). We
      assessed characteristics of individuals with a first-time antimalarial
      prescription for mefloquine, atovaquone/proguanil, chloroquine and/or proguanil,
      or doxycycline between 2001 and 2012. RESULTS: Of 165,218 individuals with a
      first-time antimalarial prescription, 108,344 (65.6%), 25,294 (15.3%), 23,195
      (14.0%), and 8385 (5.1%) were prescribed atovaquone/proguanil, mefloquine,
      doxycycline, and chloroquine and/or proguanil, respectively. Among mefloquine
      users, 7.5% had a history of a neuropsychiatric disorder (versus 12.6%-13.7%
      among other antimalarial users) and 0.04% had a history of severe liver disease
      (versus 0.04%-0.1% among other antimalarial users). A total of 19.4% mefloquine
      users were children younger than 12 years (versus 0.4%-15.8% among other
      antimalarials), and 1.3% pregnant or postpartum women (versus 0.4%-1.4% among
      users of other antimalarials). CONCLUSIONS: The most frequently prescribed
      antimalarial chemoprophylaxis was atovaquone/proguanil. Mefloquine was
      occasionally prescribed for patients with comorbidities listed as
      contraindications, but most practitioners observed contraindications. Mefloquine
      was often prescribed for children and pregnant women.

PMID- 24934851
TI  - Identification of putative pathogenic SNPs implied in schizophrenia-associated
      miRNAs.
AB  - BACKGROUND: Schizophrenia is a severe brain disorder, and SNPs (Single nucleotide
      polymorphism) in schizophrenia-associated miRNAs are believed to be one of the
      important reasons for dysregulation which might contribute to the altered
      expression of genes and ultimately result in the disease. Identification of
      causal SNPs in associated miRNAs may have certain significance in understanding
      the mechanism of schizophrenia. RESULTS: For the above purposes, a method based
      on detection of free energy change is proposed for identification of causal SNPs
      in schizophrenia-associated miRNAs. A miRNA is firstly segmented, and free energy
      change is computed after adding an SNP into a segment. The method discovers
      successfully 6 out of 32 known SNPs and some artificial SNPs could cause
      significant change in free energy, and among which, 6 known SNPs are supposed to
      be responsible for most cases of schizophrenia in population. CONCLUSIONS: The
      proposed method is not only a convenient way to discover causal SNPs in
      schizophrenia-associated miRNAs without any biochemical assay or sample
      comparison between cases and controls, but it also has high resolution for causal
      SNPs even if the SNPs are not reported for their very rare cases in the
      population. Moreover, the method can be applied to discover the causal SNPs in
      miRNAs associated with other diseases.

PMID- 24934852
TI  - Variability in urinary phthalate metabolite levels across pregnancy and sensitive
      windows of exposure for the risk of preterm birth.
AB  - BACKGROUND: Preterm birth is a significant public health problem, affecting over
      1 in 10 live births and contributing largely to infant mortality and morbidity.
      Everyday exposure to environmental chemicals such as phthalates could contribute
      to prematurity, and may be modifiable. In the present study we examine
      variability in phthalate exposure across gestation and identify windows of
      susceptibility for the relationship with preterm birth. METHODS: Women were
      recruited early in pregnancy as part of a prospective, longitudinal birth cohort
      at the Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were
      collected at up to 4 time points during gestation for phthalate measurement, and
      birth outcomes were recorded at delivery. From this population we selected all
      130 cases of preterm birth, defined as delivery before 37 weeks of completed
      gestation, as well as 352 random controls. RESULTS: Urinary phthalate metabolite
      levels were moderately variable over pregnancy, but levels measured at multiple
      time points were associated with increased odds of preterm birth. Adjusted odds
      ratios (aOR) for spontaneous preterm birth were strongest in association with
      phthalate metabolite concentrations measured at the beginning of the third
      trimester (aOR for summed di-2-ethylhexyl phthalate metabolites [?DEHP]=1.33, 95%
      confidence interval [CI]=1.02, 1.73). Odds ratios for placental preterm birth,
      defined as delivery with presentation of preeclampsia or intrauterine growth
      restriction, were slightly elevated in the first trimester for DEHP metabolites
      (aOR for ?DEHP=1.33, 95% CI=0.99, 1.78). CONCLUSIONS: Pregnant women with
      exposure to phthalates both early and late in pregnancy are at an increased risk
      of delivering preterm, but mechanisms may differ based on etiology.

PMID- 24934853
TI  - Prenatal exposure to organophosphate pesticides and reciprocal social behavior in
      childhood.
AB  - Prenatal exposure to organophosphate pesticides (OPs) has been associated with
      adverse neurodevelopmental outcomes in childhood, including low IQ, pervasive
      developmental disorder (PDD), attention problems and ADHD. Many of these
      disorders involve impairments in social functioning. Thus, we investigated the
      relationship between biomarkers of prenatal OP exposure and impaired reciprocal
      social behavior in childhood, as measured by the Social Responsiveness Scale
      (SRS). Using a multi-ethnic urban prospective cohort of mother-infant pairs in
      New York City recruited between 1998 and 2002 (n=404) we examined the relation
      between third trimester maternal urinary levels of dialkylphosphate (SigmaDAP) OP
      metabolites and SRS scores among 136 children who returned for the 7-9year visit.
      Overall, there was no association between OPs and SRS scores, although in
      multivariate adjusted models, associations were heterogeneous by race and by sex.
      Among blacks, each 10-fold increase in total diethylphosphates (SigmaDEP) was
      associated with poorer social responsiveness (beta=5.1 points, 95% confidence
      interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or
      for total SigmaDAP or total dimethylphosphate (SigmaDMP) biomarker levels.
      Additionally, stratum-specific models supported a stronger negative association
      among boys for SigmaDEPs (beta=3.5 points, 95% CI 0.2, 6.8), with no notable
      association among girls. Our results support an association of prenatal OP
      exposure with deficits in social functioning among blacks and among boys,
      although this may be in part reflective of differences in exposure patterns. 

PMID- 24934854
TI  - Development and application of an inhalation bioaccessibility method (IBM) for
      lead in the PM10 size fraction of soil.
AB  - An approach for assessing the inhalation bioaccessibility of Pb in the PM10 size
      fraction is presented, using an in vitro simulated epithelial lung fluid to
      represent the extracellular environment of the lung. The developed inhalation
      bioaccessibility method (IBM) is applied to a range of urban surface soils and
      mining wastes obtained from Mitrovica, Kosovo, a site where impacts upon human
      health following exposure to Pb have been internationally publicised. All Pb
      determinations were undertaken by inductively coupled plasma mass spectrometry
      (ICP-MS). The pseudo-total concentration of Pb (microwave acid digestion using
      aqua-regia) varied between matrices: smelter (20,900-72,800mgkg(-1)), topsoil
      (274-13,700mgkg(-1)), and tailings (2990mgkg(-1)-25,300mgkg(-1)). The in vitro
      inhalation bioaccessibility was typically several orders of magnitude lower:
      smelter (7.0-965mgkg(-1)), topsoil (9.8-1060mgkg(-1)), and tailings (0.7mgkg(-1)
      49.2mgkg(-1)). The % inhalation bioaccessibility ranged from 0.02 to 11.0%, with
      the higher inhalation bioaccessible Pb concentrations being observed for samples
      from the Bosniak Mahalla area of Mitrovica (an area proposed for the relocation
      of internally displaced peoples). The estimated inhalation dose (for adults)
      calculated from the PM10 pseudo-total Pb concentration ranged from 0.369 to
      1.284MUgkg(-1)BWday(-1) (smelter), 0.005-0.242MUgkg(-1)BWday(-1) (topsoil), and
      0.053-0.446MUgkg(-1)BWday(-1) (tailings). When daily inhalation doses were
      calculated using the bioaccessible Pb concentration the modelled exposure doses
      were much lower: smelter (0.0001-0.0170MUgkg(-1)BWday(-1)), topsoil (0.0002
      0.0187MUgkg(-1)BWday(-1)) and tailings (0.0001-0.0009MUgkg(-1)BWday(-1)).
      Modelled for the neutral pH conditions of the interstitial lung environment, the
      results indicate a low potential inhalation bioaccessibility for Pb in these
      samples. Given the already elevated environmental Pb burden experienced by the
      local population, where significant prolonged dust or particulate generating
      activities are taking place, or where the inhaled particles are phagocytized,
      then inhalation exposure has the potential to significantly add to the overall Pb
      burden. Such data are important for local policy makers to better enable them to
      assess risk, especially in areas where soils/dusts have elevated levels of
      contamination. 

PMID- 24934855
TI  - Occurrences, toxicities, and ecological risks of benzophenone-3, a common
      component of organic sunscreen products: a mini-review.
AB  - Benzophenone-3 (BP-3) has been widely used in sunscreens and many other consumer
      products, including cosmetics. The widespread use of BP-3 has resulted in its
      release into the water environment, and hence its potential impact on aquatic
      ecosystem is of concern. To better understand the risk associated with BP-3 in
      aquatic ecosystems, we conducted a thorough review of available articles
      regarding the physicochemical properties, toxicokinetics, environmental
      occurrence, and toxic effects of BP-3 and its suspected metabolites. BP-3 is
      lipophilic, photostable, and bioaccumulative, and can be rapidly absorbed via
      oral and dermal routes. BP-3 is reported to be transformed into three major
      metabolites in vivo, i.e., benzophenone-1 (BP-1), benzophenone-8 (BP-8), and
      2,3,4-trihydroxybenzophenone (THB). BP-1 has a longer biological half-life than
      its parent compound and exhibits greater estrogenic potency in vitro. BP-3 has
      been detected in water, soil, sediments, sludge, and biota. The maximum detected
      level in ambient freshwater and seawater is 125ng/L and 577.5ng/L, respectively,
      and in wastewater influent is 10,400ng/L. The major sources of BP-3 are reported
      to be human recreational activities and wastewater treatment plant (WWTP)
      effluents. BP-3 and its derivatives have been also detected in fish lipid. In
      humans, BP-3 has been detected in urine, serum, and breast milk samples
      worldwide. BP-1 has also been detected in placental tissues of delivering women.
      While sunscreens and cosmetics are known to be major sources of exposure, the
      fact that BP-3 has been detected frequently among young children and men suggests
      other sources. An increasing number of in vitro studies have indicated the
      endocrine disrupting capacity of BP-3. Based on a receptor binding assay, BP-3
      has shown strong anti-androgenic and weak estrogenic activities but at the same
      time BP-3 displays anti-estrogenic activity as well. Predicted no effect
      concentration (PNEC) for BP-3 was derived at 1.32MUg/L. The levels observed in
      ambient water are generally an order of magnitude lower than the PNEC, but in
      wastewater influents, hazard quotients (HQs) greater than 1 were noted.
      Considering limited ecotoxicological information and significant seasonal and
      spatial variations of BP-3 in water, further studies on environmental monitoring
      and potential consequences of long-term exposure in aquatic ecosystem are
      warranted. 

PMID- 24934856
TI  - The crab Carcinus maenas as a suitable experimental model in ecotoxicology.
AB  - Aquatic ecotoxicology broadly focuses on how aquatic organisms interact with
      pollutants in their environment in order to determine environmental hazard and
      potential risks to humans. Research has produced increasing evidence on the
      pivotal role of aquatic invertebrates in the assessment of the impact of
      pollutants on the environment. Its potential use to replace fish bioassays, which
      offers ethical advantages, has already been widely studied. Nevertheless, the
      selection of adequate invertebrate experimental models, appropriate experimental
      designs and bioassays, as well as the control of potential confounding factors in
      toxicity testing are of major importance to obtain scientifically valid results.
      Therefore, the present study reviews more than four decades of published research
      papers in which the Green crab Carcinus maenas was used as an experimental test
      organism. In general, the surveyed literature indicates that C. maenas is
      sensitive to a wide range of aquatic pollutants and that its biological responses
      are linked to exposure concentrations or doses. Current scientific knowledge
      regarding the biology and ecology of C. maenas and the extensive studies on
      toxicology found for the present review recognise the Green crab as a reliable
      estuarine/marine model for routine testing in ecotoxicology research and
      environmental quality assessment, especially in what concerns the application of
      the biomarker approach. Data gathered provide valuable information for the
      selection of adequate and trustworthy bioassays to be used in C. maenas toxicity
      testing. Since the final expression of high quality testing is a reliable
      outcome, the present review recommends gender, size and morphotype separation in
      C. maenas experimental designs and data evaluation. Moreover, the organisms'
      nutritional status should be taken into account, especially in long-term studies.
      Studies should also consider the crabs' resilience when facing historical and
      concurrent contamination. Finally, experimental temperature and salinity should
      be harmonised so as to obtain reliable comparisons between different studies.
      Concerning future reaserch areas, data gathered in the present review reveals
      that in vitro assays derived from C. maenas are still lacking. Also, a complete
      C. maenas genome sequencing programme will be essencial for cutting-edge reseach.

PMID- 24934857
TI  - Attributing population-scale human exposure to various source categories: merging
      exposure models and biomonitoring data.
AB  - Information about the distribution of chemical-production mass with respect to
      use and release is a major and unavailable input for calculating population-scale
      exposure estimates. Based on exposure models and biomonitoring data, this study
      evaluates the distribution of total production volumes (and environmental
      releases if applicable) for a suite of organic compounds. We used Bayesian
      approaches that take the total intake from our exposure models as the prior
      intake distribution and the intake inferred from measured biomarker
      concentrations in the NHANES survey as the basis for updating. By carrying out a
      generalized sensitivity analysis, we separated the input parameters for which the
      modeled range of the total intake is within a factor of 2 of the intake inferred
      from biomonitoring data and those that result in a range greater than a factor of
      2 of the intake. This analysis allows us to find the most sensitive (or
      important) parameters and the likelihood of emission rates for various source
      emission categories. Pie charts of contribution from each exposure pathway
      indicate that chemical properties are a primary determinant of the relative
      contribution of each exposure pathway within a given class of compounds. For
      compounds with relatively high octanol-water partition coefficients (Kow) such as
      di-2-ethylhexyl phthalate (DEHP), pyrene, 2,2',4,4'-tetrabromodiphenyl ether
      (PBDE-47), and 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE-153), more than 80%
      of exposure derives from outdoor food ingestion and/or indoor dust ingestion. In
      contrast, for diethyl phthalate (DEP), di-iso-butyl phthalate (DiBP), di-n-butyl
      phthalate (DnBP), butylbenzyl phthalate (BBP), and naphthalene, all relatively
      volatile compounds, either inhalation (indoor and outdoor) or dermal uptake from
      direct consumer use is the dominant exposure pathway. The approach of this study
      provides insights on confronting data gaps to improve population-scale exposure
      estimates used for high-throughput chemical prioritization. 

PMID- 24934858
TI  - [The use of transesophageal echocardiography to guide the trans-septal puncture.
      Practical guide, tips and tricks].
AB  - Transesophageal echocardiography is very useful to guide transseptal puncture for
      left atrial ablation procedures. This paper is a practical guide for the
      ultrasonographer who seeks to meet the expectations of the electrophysiologist,
      but also for young EP's in order to improve their understanding of the
      echocardiographical views and to ameliorate the communication between the two
      specialists. The tips and tricks of all the steps of the exam are presented. 

PMID- 24934859
TI  - Responsiveness of the ten-metre walk test, Step Test and Motor Assessment Scale
      in inpatient care after stroke.
AB  - BACKGROUND: Responsiveness of a measurement tool is its ability to detect change
      over time. The aim of this study was to determine the responsiveness and
      floor/ceiling effects of the ten-metre walk test (10mWT), Step Test and Motor
      Assessment Scale (MAS) lower limb items. METHODS: An inception cohort study was
      conducted, including 190 stroke survivors admitted to a comprehensive stroke
      unit. The 10mWT, Step Test and MAS were administered within 48 hours of admission
      and repeated in the 48 hours before discharge. Responsiveness was analysed with
      Effect Size (ES), Standardised Response Mean (SRM) and a median-based Effect Size
      (mES). Floor/ceiling effects were calculated as the percentage of participants
      scoring the lowest/highest possible scores. RESULTS: Responsiveness of each
      outcome measure varied according to the statistic used. Values for the 10mWT were
      ES 1.44, SRM 0.93, mES 0.45; the step test ES 1.99, SRM 0.88, mES 0.36; MAS sit
      to-stand (item 4) score ES 1.27, SRM 1.00, mES 0.50; and for MAS item 5 (walking)
      ES 1.43, SRM 1.10, mES 0.50. The MAS item 3 (sitting balance) was moderately
      responsive in all analyses (ES 0.72, SRM 0.71, mES 0.50). The MAS mobility score
      (summed items 3-5) consistently showed large responsiveness (ES 1.42, SRM 1.16,
      mES 0.92). The Step Test had the highest proportion of participants who didn't
      change (46%) and item 4 of the MAS showed the largest ceiling effect on discharge
      (44%). CONCLUSIONS: Most measures were able to detect change in motor performance
      during inpatient stroke rehabilitation but the MAS mobility score was the only
      measure that demonstrated large responsiveness and no marked floor or ceiling
      effects.

PMID- 24934861
TI  - Listeria exploits damage and death to spread bad news.
AB  - Pathogenic Listeria monocytogenes replicates within the host cytosol; little is
      known about how it transits from cell to cell, spreading infection. A recent
      study implicates infection-induced membrane damage as a trigger for
      efferocytosis, the recognition and uptake of dead cells, thereby tricking
      neighboring cells into taking up the invader. 

PMID- 24934862
TI  - Dissecting the steps of CO2 reduction: 2. The interaction of CO and CO2 with
      Pd/gamma-Al2O3: an in situ FTIR study.
AB  - Alumina supported Pd catalysts with metal loadings of 0.5, 2.5 and 10 wt% were
      investigated by in situ FTIR spectroscopy in order to understand the nature of
      adsorbed species formed during their exposure to CO2 and CO. Exposing the
      annealed samples to CO2 at 295 K resulted in the formation of alumina support
      bound surface species only: linear adsorbed CO2, bidentate carbonates and
      bicarbonates. Room temperature exposure of all three samples to CO produced IR
      features characteristic of both ionic and metallic Pd, as well as bands we
      observed upon CO2 adsorption (alumina support-bound species). Low temperature
      (100 K) adsorption of CO on the three samples provided information about the
      state of Pd after oxidation and reduction. Oxidized samples contained exclusively
      ionic Pd, while mostly metallic Pd was present in the reduced samples. Subsequent
      annealing of the CO-saturated samples revealed the facile (low temperature)
      reduction of PdO(x) species by adsorbed CO. This process was evidenced by the
      variations in IR bands characteristic of ionic and metallic Pd-bound CO, as well
      as by the appearance of IR bands associated with CO2 adsorption as a function of
      annealing temperature. Samples containing oxidized Pd species (oxidized, annealed
      or reduced) always produced CO2 upon their exposure to CO, while no CO2-related
      surface entities were observed on samples having only fully reduced (metallic)
      Pd.

PMID- 24934860
TI  - Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies
      senescence of human adult stem cells.
AB  - Human endometrium-derived mesenchymal stem cells (hMESCs) enter the premature
      senescence under sublethal oxidative stress, however underlying mechanism remains
      unknown. Here, we showed that exogenous H2O2 induces a rapid phosphorylation and
      co-localization of ATM, H2A.X, 53BP1 leading to DNA damage response (DDR)
      activation. DDR was accompanied with nuclear translocation of p-p53 followed by
      up-regulation of p21Waf1 and the permanent hypophosphorylation of pRb.
      Additionally, the increased p38MAPK/MAPKAPK-2 activation persisted in H2O2
      treated cells. We suggest that both p53/p21/pRb and p38MAPK/MAPKAPK-2 pathways
      are responsible for establishing an irreversible cell cycle arrest that is
      typical of senescence. The process of further stabilization of senescence
      required prolonged DDR signaling activation that was provided by the permanent
      ROS production which in turn was regulated by both p38MAPK and the increased
      functional mitochondria. To reverse senescence, the pharmacological inhibition of
      p38MAPK was performed. Cell treatment with SB203580 was sufficient to recover
      partially senescence phenotype, to block the ROS elevation, to decrease the
      mitochondrial function, and finally to rescue proliferation. Thus, suppression of
      the p38MAPK pathway resulted in a partial prevention of H2O2-induced senescence
      of hMESCs. The current study is the first to reveal the molecular mechanism of
      the premature senescence of hMESCs in response to oxidative stress. 

PMID- 24934863
TI  - Third-space fluid distribution of pemetrexed in non-small cell lung cancer
      patients.
AB  - AIM: Hydrophilic drugs particularly those with low plasma protein binding may
      accumulate in third-space fluid in the body. Cytotoxic drugs like methotrexate
      (MTX) cause damage in the tissue, and evacuation of the third-space fluid in
      pleura is strongly recommended before new dosing. Pemetrexed (PEM) is a multi
      targeted antifolate similar to MTX approved for the treatment for malignant
      pleural mesothelioma and non-small cell lung cancer. Current recommendations for
      patients receiving treatment with PEM prescribe draining of the pleural fluid.
      This is based upon the recommendations for MTX and not directly to any specific
      findings relating to PEM. The recommendations are the same because PEM is an
      analogue of MTX; the molecular structures and pharmacokinetic parameters are
      similar. However, since draining the pleural fluid is painful and cancer patient
      are particularly susceptible to infection subsequently, it is relevant to examine
      the recommendations for PEM explicitly. METHOD: Eight patients treated with a 500
      mg/m(2) PEM combined with platinum salt were examined. Plasma samples were first
      collected in relation to the start of PEM infusion. Thereafter, plasma and pleura
      samples were taken at various times after drug infusion from each patient; in two
      patients, sampling was done twice but on different occasions. The quantitative
      determination of PEM was performed with reversed-phase high-performance liquid
      chromatography, and sample preparation was performed using protein precipitation
      with perchloric acid. Pharmacokinetic analysis was performed using a non
      compartment method as well a two-compartment model. RESULTS: The results were
      calculated from 10 samples taken from eight patients, where data from one patient
      point were excluded as the patient had impaired renal function, and three samples
      were reported as below limit of quantification. The plasma PEM pharmacokinetics
      calculated showed an elimination half-life (t 1/2 elimination) of 3.2 h and
      distribution half-life (t 1/2-distribution) of 6 min. Clearance (CL) was 5.1 L/h,
      central volume of distribution (V(central)) 23.2 L and peripheral volume
      distribution (V(peripheral)) 10.6 L, and the area under the curve was 186 MUg
      h/mL. Using non-compartment methods, an elimination half-life of 3.1 h and an
      apparent CL of 3.2 L/h were measured, whereas an apparent steady-state volume
      became 14.2 L. The pleura concentrations were only half of simultaneous plasma
      concentrations, and elimination half-life was 3.15 h. CONCLUSION: Pemetrexed is
      not likely to accumulate in the pleural fluid, and evacuation of fluid might not
      be necessary. Further investigation is needed to recommend no drainage of the
      fluid, i.e., in patients with renal impairment.

PMID- 24934864
TI  - Comparative pharmacokinetic/pharmacodynamic characterisation of a new pegylated
      recombinant E. coli L-asparaginase preparation (MC0609) in Beagle dog.
AB  - PURPOSE: A new pegylated recombinant L-asparaginase (MC0609) was designed to
      improve pharmacokinetic characteristics and to further reduce immunogenicity in
      comparison with the currently marketed pegylated Escherichia coli L-asparaginase
      (pegaspargase, Oncaspar((r))). METHODS: Comparative pharmacokinetics (PK),
      bioavailability, pharmacodynamics and immunogenicity studies were performed in
      CD((r)) rats and Beagle dogs after intravenous (i.v.) and intramuscular (i.m.)
      single-dose administration of MC0609 or Oncaspar((r)). Bioanalytical data on
      enzymatic activity in serum of animals were used to develop a population
      pharmacokinetic (PopPK) model to simulate different dosages of MC0609 comparable
      to the activity time profile of Oncaspar((r)). RESULTS: In contrast to
      Oncaspar((r)), which showed an accelerated elimination over time, a constant
      serum elimination of enzymatic activity over time was seen for MC0609. Linear PK
      of MC0609 resulted in a prolonged and dose-dependent duration of enzymatic
      activity and longer depletion of L-asparagine in peripheral blood. The different
      PK characteristics of MC0609 and Oncaspar((r)) were confirmed by PopPK analysis
      and model development. The PK parameters of Oncaspar((r)) in dog scaled to body
      surface area were in the same range than the parameters determined in paediatric
      acute lymphoblastic leukaemia patients. Therefore, the dog is considered a
      clinically relevant model for PK evaluation of Oncaspar((r)). Distinct
      differences in immunogenic potential of both preparations were detected after
      single-dose administration of a therapeutic dose to dogs. An absolute
      bioavailability of 66 % was calculated for the intramuscular administration of
      MC0609. CONCLUSIONS: The new pegylated recombinant L-asparaginase preparation
      MC0609 revealed striking differences in PK/PD properties compared with
      Oncaspar((r)) in rat and dog.

PMID- 24934865
TI  - Impact of patient ethnicity on the metabolic and immunologic effects of PI3K-mTOR
      pathway inhibition in patients with solid tumor malignancies.
AB  - PURPOSE: Inhibition of the phosphatidylinositol 3-kinase (PI3K)/mammalian target
      of rapamycin (mTOR) pathway is associated with metabolic and immunologic
      perturbations that impact drug tolerability. Here, we studied whether PI3
      kinase/mTOR pathway inhibitors are associated with greater metabolic impact and
      decreased tolerability in Asian patients. METHODS: A retrospective analysis was
      conducted of consecutive patients with advanced malignancies treated on phase 1
      trials of PI3K/mTOR inhibitors. Adverse events related to PI3K/mTOR inhibition,
      fasting plasma glucose (FPG), insulin, and c-peptide levels, hemoglobin A1c
      (HgbA1c), and T cell subsets were prospectively collected. Mann-Whitney and Chi
      square tests were used to compare continuous and categorical variables,
      respectively, between Asian and Caucasian patients. RESULTS: A total of 103
      patients (31 Asian; 72 Caucasian) were treated consecutively across five clinical
      trials. Baseline age, gender distribution, and metabolic parameters were
      comparable with the exception of lower median body mass index (BMI) in Asian
      patients (23.0 vs. 24.8 kg/m(2), p = 0.024). There were no differences in drug
      tolerability, adherence, or duration of therapy. Asian patients experienced a
      higher incidence of grade >= 2 hyperglycemia (37.5 vs. 18.1%, p = 0.03), and
      greater increases in FPG, HgbA1c, and insulin resistance. No differences in
      incidence or severity of mucositis, rash, or pneumonitis were observed. Drug
      effects on neutrophils, lymphocytes, and T cell subsets were similar.
      CONCLUSIONS: PI3K/mTOR inhibitors have greater glycemic impact in Asian patients,
      despite similar baseline metabolic parameters, comparable dose intensity, and a
      lower median BMI. Further studies are warranted to explore the mechanisms
      underlying these differences and optimize dosing in Asian patients.

PMID- 24934866
TI  - Evaluation of pharmacokinetics and safety of ponatinib in subjects with chronic
      hepatic impairment and matched healthy subjects.
AB  - PURPOSE: This study evaluated the effects of chronic hepatic impairment on the
      single-dose pharmacokinetics (PK) of the tyrosine kinase inhibitor ponatinib.
      METHODS: Subjects (n = 16) had Child-Pugh class A (mild, n = 6), B (moderate, n =
      6), or C (severe, n = 4) hepatic impairment and were matched with healthy
      controls (n = 8). Each subject received a single oral dose of ponatinib 30 mg
      under fasting conditions, and PK parameters were assessed in blood samples
      collected through 96 h post-dose. RESULTS: Ponatinib maximum plasma
      concentrations (C max) were observed after 5-6 h in Child-Pugh A, Child-Pugh B,
      and healthy subjects, and after ~3 h in Child-Pugh C subjects. The estimated %
      geometric mean ratios for C max, area under the plasma concentration-time curves
      from time zero to last observation (AUC0-t ) and to infinity (AUC0-infinity)
      suggested a slightly lower exposure in Child-Pugh B (61.4, 89.1, and 90.6%,
      respectively) and Child-Pugh C subjects (62.8, 77.1, and 79.4%) versus healthy
      subjects. Child-Pugh A subjects had similar estimated % geometric mean ratio for
      C max (106.7%), and slightly greater estimated % geometric mean ratios for AUC0-t
      (133.0%) and AUC0-infinity (122.8%), versus healthy subjects. Mean elimination
      half-life was extended in subjects with hepatic impairment (43-47 vs 36 h).
      Ponatinib was generally well tolerated. A single serious AE (pancreatitis) in the
      Child-Pugh C group resolved with treatment. DISCUSSION: As no major differences
      in ponatinib single-dose PK were observed in patients with hepatic impairment
      versus healthy subjects, a reduction of ponatinib starting dose in these patients
      is not necessary, but caution is recommended when administering ponatinib to
      these patients.

PMID- 24934867
TI  - Does intramuscular thermal feedback modulate eccrine sweating in exercising
      humans?
AB  - AIM: Few investigators have considered the possibility that skeletal muscles
      might contain thermosensitive elements capable of modifying thermoeffector
      responses. In this experiment, the temporal relationships between dynamic changes
      in deep-body and intramuscular temperatures and eccrine sweat secretion were
      explored during rhythmical and reproducible variations in heat production.
      METHODS: Eight subjects performed semi-recumbent cycling (25  degrees C) at a
      constant load to first establish whole-body thermal and sudomotor steady states
      (35 min), followed by a 24-min block of sinusoidal workload variations (three, 8
      min periods) and then returning to steady-state cycling (20 min). Individual
      oesophageal, mean skin and intramuscular (vastus lateralis) temperatures were
      independently cross-correlated with simultaneously measured forehead sweat rates
      to evaluate the possible thermal modulation of sudomotor activity. RESULTS: Both
      intramuscular and oesophageal temperatures showed strong correlations with
      sinusoidal variations in sweating with respective maximal cross-correlation
      coefficients of 0.807 (+/-0.044) and 0.845 (+/-0.035), but these were not
      different (P = 0.40). However, the phase delay between intramuscular temperature
      changes and sweat secretion was significantly shorter than the delay between
      oesophageal temperature and sweating [25.6 s (+/-12.6) vs. 46.9 s (+/-11.3); P =
      0.03]. CONCLUSION: The temporal coupling of eccrine sweating to intramuscular
      temperature, combined with a shorter phase delay, was consistent with the
      presence of thermosensitive elements within skeletal muscles that appear to
      participate in the modulation of thermal sweating.

PMID- 24934868
TI  - Non-codified traditional medicine practices from Belgaum Region in Southern
      India: present scenario.
AB  - BACKGROUND: Traditional medicine in India can be classified into codified
      (Ayurveda, Unani, Siddha, Homeopathy) and non-codified (folk medicine) systems.
      Both the systems contributing equally to the primary healthcare in India. The
      present study is aimed to understand the current scenario of medicinal practices
      of non-codified system of traditional medicine in Belgaum region, India. METHODS:
      The study has been conducted as a basic survey of identified non-codified
      traditional practitioners by convenience sampling with semi structured, open
      ended interviews and discussions. The learning process, disease diagnosis,
      treatment, remuneration, sharing of knowledge and socio-demographic data was
      collected, analysed and discussed. RESULTS: One hundred and forty traditional
      practitioners were identified and interviewed for the present study. These
      practitioners are locally known as "Vaidya". The study revealed that the non
      codified healthcare tradition is practiced mainly by elderly persons in the age
      group of 61 years and above (40%). 73% of the practitioners learnt the tradition
      from their forefathers, and 19% of practitioners developed their own practices
      through experimentation, reading and learning. 20% of the practitioners follow
      distinctive "Nadi Pariksha" (pulse examination) for disease diagnosis, while
      others follow bodily symptoms and complaints. 29% of the traditional
      practitioners do not charge anything, while 59% practitioners receive money as
      remuneration.Plant and animal materials are used as sources of medicines, with a
      variety of preparation methods. The preference ranking test revealed higher
      education and migration from villages are the main reasons for decreasing
      interest amongst the younger generation, while deforestation emerged as the main
      cause of medicinal plants depletion. CONCLUSION: Patrilineal transfer of the
      knowledge to younger generation was observed in Belgaum region. The observed
      resemblance in disease diagnosis, plant collection and processing between non
      codified traditional system of medicine and Ayurveda require further methodical
      studies to establish the relationship between the two on a more objective basis.
      However, the practice appears to be at crossroads with threat of extinction,
      because of non-inheritance of the knowledge and non-availability of medicinal
      plants. Hence conservation strategies for both knowledge and resources at
      societal, scientific and legislative levels are urgently required to preserve the
      traditional wisdom.

PMID- 24934869
TI  - Orphans and new gene origination, a structural and evolutionary perspective.
AB  - The frequency of de novo creation of proteins has been debated. Early it was
      assumed that de novo creation should be extremely rare and that the vast majority
      of all protein coding genes were created in early history of life. However, the
      early genomics era lead to the insight that protein coding genes do appear to be
      lineage-specific. Today, with thousands of completely sequenced genomes, this
      impression remains. It has even been proposed that the creation of novel genes, a
      continuous process where most de novo genes are short-lived, is as frequent as
      gene duplications. There exist reports with strongly indicative evidence for de
      novo gene emergence in many organisms ranging from Bacteria, sometimes generated
      through bacteriophages, to humans, where orphans appear to be overexpressed in
      brain and testis. In contrast, research on protein evolution indicates that many
      very distantly related proteins appear to share partial homology. Here, we
      discuss recent results on de novo gene emergence, as well as important technical
      challenges limiting our ability to get a definite answer to the extent of de novo
      protein creation. 

PMID- 24934870
TI  - Evaluation of 4-bromophenol biodegradation in mixed pollutants system by
      Arthrobacter chlorophenolicus A6 in an upflow packed bed reactor.
AB  - Bromophenol is listed as priority pollutant by U.S. EPA, however, there is no
      report so far on its removal in mixed pollutants system by any biological reactor
      operated in continuous mode. Furthermore, bromophenol along with chlorophenol and
      nitrophenol are usually the major constituents of paper pulp and pesticide
      industrial effluent. The present study investigated simultaneous biodegradation
      of these three pollutants with specially emphasis on substrate competition and
      crossed inhibition by Arthrobacter chlorophenolicus A6 in an upflow packed bed
      reactor (UPBR). A 2(3) full factorial design was employed with these pollutants
      at two different levels by varying their influent concentration in the range of
      250-450 mg l(-1). Almost complete removal of all these pollutants and 97 %
      effluent toxicity removal were achieved in the UPBR at a pollutant loading rate
      of 1707 mg l(-1) day(-1) or lesser. However, at higher loading rates, the reactor
      performance deteriorated due to transient accumulation of toxic intermediates.
      Statistical analysis of the results revealed a strong negative interaction of 4
      CP on 4-NP biodegradation. On the other hand, interaction effect between 4-CP and
      4-BP was found to be insignificant. Among these three pollutants 4-NP
      preferentially degraded, however, 4-CP exerted more inhibitory effect on 4-NP
      biodegradation. This study demonstrated the potential of A. chlorophenolicus A6
      for biodegradation of 4-BP in mixed pollutants system by a flow through UPBR
      system.

PMID- 24934872
TI  - The EGFR demonstrates linear signal transmission.
AB  - Cells sense information encoded in extracellular ligand concentrations and
      process it using intracellular signalling cascades. Using mathematical modelling
      and high-throughput imaging of individual cells, we studied how a transient
      extracellular growth factor signal is sensed by the epidermal growth factor
      receptor system, processed by downstream signalling, and transmitted to the
      nucleus. We found that transient epidermal growth factor signals are linearly
      translated into an activated epidermal growth factor receptor integrated over
      time. This allows us to generate a simplified model of receptor signaling where
      the receptor acts as a perfect sensor of extracellular information, while the
      nonlinear input-output relationship of EGF-EGFR triggered signalling is a
      consequence of the downstream MAPK cascade alone. 

PMID- 24934871
TI  - Mobility and one-year mortality of stroke patients after hip-fracture surgery.
AB  - BACKGROUND: History of stroke is a risk factor for hip fracture. We investigated
      one-year mortality and change of mobility differences between stroke patients and
      non-stroke patients after hip-fracture surgery. METHODS: We retrospectively
      evaluated 548 patients who had hip-fracture surgery from May 2003 to Dec 2008 and
      were older than 50 years at the time of surgery. We identified 77 patients with a
      history of stroke and 471 patients with no history of stroke. We compared
      postoperative change of mobility and 1-year mortality for the two groups.
      RESULTS: Although stroke patients had lower preinjury mobility (p < 0.001) and
      higher American Society of Anesthesiologists score (p < 0.001), 1-year mortality
      and the decrease of mobility were similar to those for non-stroke patients.
      CONCLUSIONS: History of stroke did not affect 1-year mortality and the decrease
      of mobility after hip fracture. LEVEL OF EVIDENCE: Therapeutic level III.

PMID- 24934874
TI  - Prevention: High-potency statins associated with increased diabetes risk.

PMID- 24934873
TI  - Fecal carriage of extended-spectrum beta-lactamases and AmpC-producing
      Escherichia coli in a Libyan community.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs), including the AmpC type,
      are important mechanisms of resistance among Enterobacteriaeceae. CTX-M type
      extended-spectrum beta- lactamases, of which there are now over 90 variants, are
      distributed globally, yet appear to vary in regional distribution. AmpC beta
      lactamases hydrolyze third generation cephalosporins, but are resistant to
      inhibition by clavulanate or other beta-lactamase inhibitors in vitro. Fecal
      carriage and rates of colonization by bacteria harboring these resistance
      mechanisms have been reported in patients with community-acquired infections and
      in healthy members of their households. Expression of these ESBLs compromises the
      efficacy of current antibacterial therapies, potentially increasing the
      seriousness of hospital- and community-acquired Escherichia coli (E. coli)
      infections.To investigate the occurrence of ESBL-producing E. coli in human fecal
      flora isolated from two pediatric populations residing in the Libyan cities
      Zleiten and Abou El Khoms. Isolates were further studied to characterize genes
      encoding beta-lactam resistance, and establish genetic relationships. METHODS:
      Antibiotic resistance profiles of phenotypically characterized E. coli isolates
      recovered from the stools of 243 Libyan children during two surveillance periods
      in 2001 and 2007 were determined by the disk diffusion method. ESBL-screening was
      performed using the cephalosporin/clavulanate double synergy disc method, and the
      AmpC-phenotype was confirmed by the aminophenyl-boronic acid test. ESBL genes
      were molecularly characterized. Phylogenetic group and multilocus sequence typing
      (MLST) were determined for ESBL-producing isolates and PFGE was performed to
      compare banding profiles of some dominant strains. RESULTS: ESBLs were identified
      in 13.4% (18/134) of E. coli isolates, and nine isolates (6.7%) demonstrated AmpC
      activity; all 18 isolates contained a CTX-M gene. Three CTX-M gene families (CTX
      M-1, n=9; CTX-M-15, n=8 and CTX-M-3, n=1) were distributed in diverse E. coli
      backgrounds (phylogenetic group D, 39%; B2, 28%; B1, 22% and A, 11%). MLST
      analysis revealed 14 sequence type (ST) with six new sequence types. The gene
      encoding the CMY-2 enzyme was detected in five AmpC-positive E. coli.
      CONCLUSIONS: These results identified heterogeneous clones of CTX-M-producing E.
      coli in the fecal isolates, indicating that the intestinal tract acts as a
      reservoir for ESBL-producing organisms, and a trafficker of antibiotic resistance
      genes.

PMID- 24934875
TI  - Hypertension: Benefits of combined therapy.

PMID- 24934876
TI  - Prismatic adaptation as a novel tool to directionally modulate motor cortex
      excitability: evidence from paired-pulse TMS.
AB  - BACKGROUND: The prismatic adaptation (PA) is a visuo-motor procedure that has
      captured the attention of neuroscientists in the last decades, hence it seems to
      affect high-order cognition. However, the basic neural processes related to PA
      and its effects on cortical plasticity are not clear yet. OBJECTIVE/HYPOTHESIS:
      The aim of the present study is to explore whether PA induces a direct effect on
      the motor cortices (M1) excitability. METHODS: Fourteen healthy participants were
      submitted to paired-pulse TMS to measure short-intracortical-inhibition (SICI)
      and intracortical-facilitation (ICF) on both the left and the right M1, before
      and after PA, that could induce a leftward or rightward after-effect. RESULTS: An
      increase of intracortical-facilitation was found in the M1 contralateral to the
      after-effect direction. Moreover the extent of facilitation and of the after
      effect were correlated to each others. CONCLUSION: This finding reveals that PA
      influences M1 cortices directly, raising their excitability. The present
      investigation represents an innovative step for the understanding of
      neurophysiological processes by which PA affects brain functions.

PMID- 24934877
TI  - Protective Ag:TiO2 thin films for pressure sensors in orthopedic prosthesis: the
      importance of composition, structural and morphological features on the
      biological response of the coatings.
AB  - DC reactive magnetron sputtered Ag:TiO2 nanocomposite thin films were developed
      to be used as protective coatings in pressure sensor devices. The coatings, with
      Ag content varying from 0 to about 30 at.%, were prepared and characterized in
      order to study their biological response. The as-deposited samples were annealed
      in vacuum at 500  degrees C in order to evaluate the influence of their
      morphological and structural differences over the response elicited upon contact
      with simulated bodily fluids and cultured human cells, as well as selected
      microorganisms. The results showed that the annealing treatment produced less
      porous films with an enhanced structure, with a significant reduction in
      structural defects and improved crystallinity. Additionally, samples with higher
      Ag contents (>=12.8 at.%) exhibited Ag agglomerates/clusters at the surface, a
      result anticipated from the XRD data. The crystallization of the TiO2 matrix was
      also observed by XRD analysis, albeit delayed by the dispersion of Ag into the
      matrix. Biological characterization showed that the antimicrobial activity and
      cytotoxicity of the coatings were directly related with their composition,
      closely followed by the particular structural and morphological features, namely
      those resulting from annealing process. 

PMID- 24934878
TI  - Beyond a warming fingerprint: individualistic biogeographic responses to
      heterogeneous climate change in California.
AB  - Understanding recent biogeographic responses to climate change is fundamental for
      improving our predictions of likely future responses and guiding conservation
      planning at both local and global scales. Studies of observed biogeographic
      responses to 20th century climate change have principally examined effects
      related to ubiquitous increases in temperature - collectively termed a warming
      fingerprint. Although the importance of changes in other aspects of climate -
      particularly precipitation and water availability - is widely acknowledged from a
      theoretical standpoint and supported by paleontological evidence, we lack a
      practical understanding of how these changes interact with temperature to drive
      biogeographic responses. Further complicating matters, differences in life
      history and ecological attributes may lead species to respond differently to the
      same changes in climate. Here, we examine whether recent biogeographic patterns
      across California are consistent with a warming fingerprint. We describe how
      various components of climate have changed regionally in California during the
      20th century and review empirical evidence of biogeographic responses to these
      changes, particularly elevational range shifts. Many responses to climate change
      do not appear to be consistent with a warming fingerprint, with downslope shifts
      in elevation being as common as upslope shifts across a number of taxa and many
      demographic and community responses being inconsistent with upslope shifts. We
      identify a number of potential direct and indirect mechanisms for these
      responses, including the influence of aspects of climate change other than
      temperature (e.g., the shifting seasonal balance of energy and water
      availability), differences in each taxon's sensitivity to climate change, trophic
      interactions, and land-use change. Finally, we highlight the need to move beyond
      a warming fingerprint in studies of biogeographic responses by considering a more
      multifaceted view of climate, emphasizing local-scale effects, and including a
      priori knowledge of relevant natural history for the taxa and regions under
      study.

PMID- 24934879
TI  - Transcriptome comparison reveals the patterns of selection in domesticated and
      wild ramie (Boehmeria nivea L. Gaud).
AB  - Ramie is an old fiber crop, cultivated for thousands of years in China. The
      cultivar ramie evolved from the wild species Qingyezhuma (QYZM, Boehmeria nivea
      var. tenacissima). However, the mechanism of domestication of this old fiber crop
      is poorly understood. In order to characterize the selective pattern in ramie
      domestication, orthologous genes between the transcriptomes of domesticated ramie
      variety Zhongzhu 1 (ZZ1) and wild QYZM were assessed using bidirectional best-hit
      method and ratio of non-synonymous (Ka) to synonymous (Ks) nucleotide
      substitutions was estimated. Sequence comparison of 56,932 and 59,246 unigenes
      from the wild QYZM and domesticated ZZ1, respectively, helped identify 10,745
      orthologous unigene pairs with a total orthologous length of 10.18 Mb. Among
      these unigenes, 85 and 13 genes were found to undergo significant purifying and
      positive selection, respectively. Most of the selected genes were homologs of
      those involved in abiotic stress tolerance or disease resistance in other plants,
      suggesting that abiotic and biotic stresses were important selective pressures in
      ramie domestication. Two genes probably related to the fiber yield of ramie were
      subjected to positive selection, which may be caused by human manipulation. Thus,
      our results show the pervasive effects of artificial and natural selections on
      the accelerated domestication of ramie from its wild relative. 

PMID- 24934880
TI  - Interprofessional learning in primary care: an exploration of the service user
      experience leads to a new model for co-learning.
AB  - BACKGROUND: Research about service user involvement in research and education
      focuses on the purpose, the methods, the barriers and the impact of their
      involvement. Few studies report on the experience of the service users who get
      involved. This paper reports an exploration of the experience of service users
      who participated in an interprofessional educational initiative in primary care -
      the Learning to Improve the Management of Back Pain in the Community (LIMBIC)
      project. Service users attended workshops with practice teams and assisted them
      in developing small scale quality improvement projects to improve their provision
      of care for people with back pain. OBJECTIVES: To explore the experience of
      service users involved in the LIMBIC project. DESIGN: Using the philosophical and
      methodological approaches of pragmatism this study analysed data from the wider
      LIMBIC project and collected primary data through semi structured interviews with
      service users. Secondary data were reanalysed and integrated with primary data to
      address the research question. SETTING: The study was undertaken in the primary
      health care setting. PARTICIPANTS: Patients participated as service users in
      workshops and quality improvement projects with members from their practice
      teams. METHODS: Interviews with service users were transcribed and analysed
      thematically. Document and thematic analyses of secondary data from the LIMBIC
      project included focus group transcripts, patient stories, film, emails, meeting
      notes, a wiki and educational material such as presentations. RESULTS: Themes
      identified through the analyses illustrated the importance, to the service users,
      of the sense of community, of clear communication, and of influencing change
      through involvement. A model for co-learning with service users resulted from the
      analyses. CONCLUSIONS: The experience of service users can be optimised by
      planning, preparation and support so that their wealth of expertise can be
      recognised and utilised. A model for co-learning was developed and is presented
      in this paper.

PMID- 24934881
TI  - Luteolin-phospholipid complex: preparation, characterization and biological
      evaluation.
AB  - OBJECTIVES: This study aims to develop novel carrier system incorporating
      luteolin, a poorly soluble biologically active plant active. METHODS: We
      investigated a lipid-based drug delivery system to enhance dissolution and
      absorption profile of luteolin. Luteolin was complexed with phospholipids, and
      the preparation was characterized. The formulation was evaluated for
      physicochemical properties, in-vitro solubility or release studies. In vivo anti
      inflammatory action of luteolin and its phospholipid complex was evaluated by
      using carrageenan and 12-O-tetradecanoylphorbol-13-acetate as inducers. KEY
      FINDINGS: The prepared luteolin-phospholipid complex (LPC) showed drug loading of
      about 72.64% with average particle size of 152.6 nm. The Fourier transform
      infrared spectroscopy and thermal studies confirm formation of complex. The
      solubility of luteolin as LPC was about 2.5 times higher than the solubility of
      pure luteolin in water. In the diffusion study, LPC showed 95.12% of drug release
      at the end of 2 h. Animal studies demonstrated significant differences in
      response of LPC and luteolin. CONCLUSION: LPC was successfully prepared by
      optimizing the process parameters. The resultant delivery system improved
      bioavailability and efficacy of luteolin and in the future may become an
      efficient tool for administration of luteolin.

PMID- 24934882
TI  - Stimuli-responsive blue fluorescent supramolecular polymers based on a
      pillar[5]arene tetramer.
AB  - A tetraphenylethene-bridged pillarene tetramer with aggregation-induced emission
      properties forms an A4/B2-type supramolecular polymer and a gel with a symmetric
      neutral guest linker, showing a remarkable fluorescence emission enhancement in
      solution and the solid state and a good responsiveness to temperature and solvent
      composition. 

PMID- 24934883
TI  - Prediction of fatty acid-binding residues on protein surfaces with three
      dimensional probability distributions of interacting atoms.
AB  - Protein-fatty acid interaction is vital for many cellular processes and
      understanding this interaction is important for functional annotation as well as
      drug discovery. In this work, we present a method for predicting the fatty acid
      (FA)-binding residues by using three-dimensional probability density
      distributions of interacting atoms of FAs on protein surfaces which are derived
      from the known protein-FA complex structures. A machine learning algorithm was
      established to learn the characteristic patterns of the probability density maps
      specific to the FA-binding sites. The predictor was trained with five-fold cross
      validation on a non-redundant training set and then evaluated with an independent
      test set as well as on holo-apo pair's dataset. The results showed good accuracy
      in predicting the FA-binding residues. Further, the predictor developed in this
      study is implemented as an online server which is freely accessible at the
      following website, http://ismblab.genomics.sinica.edu.tw/. 

PMID- 24934884
TI  - Quality of Lupinus albus L. (white lupin) seed: extent of genotypic and
      environmental effects.
AB  - White lupin seed can be used for traditional and functional foods or as animal
      feed. This study aimed to support lupin breeders and production stakeholders by
      assessing the extent of genotypic, environmental, and genotype * environment (GE)
      interaction effects on seed contents of oil, tocopherols (TOC), and quinolizidine
      alkaloids (QA), grain yield, and seed weight of eight elite genotypes grown in
      two climatically contrasting Italian locations for two cropping years. On
      average, plants in the subcontinental climate site exhibited higher grain yield
      and seed size, about 8% lower oil content, and almost 85% higher QA content than
      those in the Mediterranean climate site. The range of genotype means was 2.97
      5.14 t/ha for yield, 92-110 mg/g for oil, and 0.121-0.133 mg/g for TOC. TOC
      amount was largely unpredictable and featured large GE interactions that hinder
      its genetic improvement. Oil and alkaloid contents and seed size are more
      predictable and offer potential for selection. 

PMID- 24934885
TI  - From systemic hormone therapy to vaginal estrogen - a nationwide register study
      in Finland, 2003-2012.
AB  - OBJECTIVES: To assess the patterns of use of reimbursed systemic hormone therapy
      (HT) and vaginal estrogen preparations among women aged 45 and older in Finland.
      STUDY DESIGN: Reimbursed purchases of prescribed systemic HT and vaginal estrogen
      preparations for the years 2003-2012 were obtained from a nationwide prescription
      registry. Systemic preparations included estrogen patches, gels and tablets,
      tibolone, continuous combination preparations and sequential combination
      preparations. Prescribed vaginal estrogens included a vaginal ring and vaginal
      tablets. MAIN OUTCOME MEASURES: Annual period prevalence for systemic HT and
      vaginal estrogen use. RESULTS: The total prevalence of prescribed HT use remained
      relatively constant (at 26-27%) throughout the studied period, but the share of
      women using systemic preparations decreased from 21% to 12%, while the share of
      women using vaginal estrogens increased from 9% to 19%. Decreases were observed
      for all classes of systemic preparations, although the decrease was largest for
      sequential combination preparations (from 4.9% to 1.6%) and estrogen tablets
      (from 5.2% to 2.9%). Continuous combination preparations remained the most
      commonly used types of systemic preparation (5.4-4.2%). Systemic HT use decreased
      most among 45-49 year old women (9.5-4.3%), while the use of vaginal estrogens
      increased most among those aged 65 and over. CONCLUSIONS: Based on the register
      data, the trends in HT use indicate changed prescribing patterns in accordance
      with clinical guidelines. It is notable that since 2009, vaginal estrogen was
      more commonly prescribed than systemic HT.

PMID- 24934886
TI  - Efficacy and safety of garenoxacin tablets on clinically diagnosed atypical
      pneumonia: postmarketing surveillance in Japan.
AB  - We performed a postmarketing surveillance study to determine the efficacy and
      safety of the oral quinolone antibacterial agent garenoxacin (Geninax((r))
      Tablets 200 mg) against atypical pneumonia. Between October 2009 and July 2011,
      patients with community-acquired pneumonia visited 26 facilities in Japan; we
      collected survey forms from 105 of these patients who were suspected of having
      atypical pneumonia based on the Japanese Respiratory Society Guidelines for the
      Management of Community-Acquired Pneumonia in Adults. We examined the safety in
      105 patients and the efficacy in 71 patients. 1. The efficacy rates among
      patients suspected of having atypical pneumonia and those with a confirmed
      diagnosis of atypical pneumonia were 94.8% (55/58 patients) and 92.3% (12/13
      patients), respectively. The efficacy rate was 4/4 for patients in whom
      Chlamydophila pneumoniae was detected (including 1 patient with a polymicrobial
      infection with another bacterial strain) and 90% (9/10 patients) for patients in
      whom Mycoplasma pneumoniae was detected (garenoxacin was ineffective in 1 of 2
      patients with a polymicrobial infection with another bacterial strain). 2. The
      incidence of adverse drug reactions (including abnormal laboratory tests) was
      4.8% (5/105 patients). Among the adverse drug reactions, gastrointestinal
      disorders, infection and infestation, nervous system disorder, and skin and
      subcutaneous tissue disorder were observed in 2.9% of patients (3/105), 1.0%
      (1/105), 1.0% (1/105), and 1.0% (1/105), respectively. In conclusion, garenoxacin
      showed an efficacy rate of greater than 90% for suspected atypical pneumonia and
      confirmed atypical pneumonia. Garenoxacin is considered to be useful in daily
      practice.

PMID- 24934888
TI  - Statin-use debate creates furor at The BMJ.

PMID- 24934887
TI  - Efficacy and safety of garenoxacin tablets on bacterial pneumonia: postmarketing
      surveillance in Japan.
AB  - We performed a postmarketing surveillance study to determine the efficacy and
      safety of the oral quinolone antibacterial agent, garenoxacin (Geninax((r))
      Tablets 200 mg), against bacterial pneumonia. Between October 2009 and March
      2011, patients with community-acquired pneumonia visited 174 facilities in Japan;
      we collected survey forms from 739 patients of these patients who were suspected
      with bacterial pneumonia on the basis of factors, e.g., the presence of purulent
      sputum or suspected presence of bacterial pathogens in clinical specimens. We
      examined the safety in 730 patients and the efficacy in 535 patients. The
      efficacy rate of garenoxacin for bacterial pneumonia was 92.8% (479/516
      patients). The eradication rates for Streptococcus pneumoniae and Haemophilus
      influenzae, the major pathogens of bacterial pneumonia, were 98.5% (65/66
      strains) and 100% (65/65 strains), respectively. The incidence of adverse drug
      reactions (including abnormal laboratory tests) was 7.9% (58/730 patients). Among
      the main adverse drug reactions, abnormal laboratory tests were observed in 2.1%
      patients (15/730), hepatobiliary disorders were observed in 1.8% patients
      (13/730), and skin and subcutaneous tissue disorders were observed in 1.6%
      patients (12/730). In conclusion, garenoxacin showed an efficacy rate of greater
      than 90% for bacterial pneumonia and is considered to be useful in daily
      practice.

PMID- 24934889
TI  - Dermoscopy.

PMID- 24934891
TI  - Canadians call for better palliative care.

PMID- 24934892
TI  - More international grads seek residency.

PMID- 24934893
TI  - Granulocyte colony-stimulating factor therapy for stem cell mobilization
      following anterior wall myocardial infarction: the CAPITAL STEM MI randomized
      trial.
AB  - BACKGROUND: Small studies have yielded divergent results for administration of
      granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction.
      Adequately powered studies involving patients with at least moderate left
      ventricular dysfunction are lacking. METHODS: Patients with left ventricular
      ejection fraction less than 45% after anterior-wall myocardial infarction were
      treated with G-CSF (10 MUg/kg daily for 4 days) or placebo. After initial
      randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group
      completed 6-month follow-up and underwent measurement of left ventricular
      ejection fraction by radionuclide angiography. RESULTS: Baseline and 6-week mean
      ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95%
      confidence interval [CI] 32.6%-37.0%) v. 36.4% (95% CI 33.5%-39.2%) at baseline
      and 39.8% (95% CI 36.2%-43.4%) v. 43.1% (95% CI 39.2%-47.0%) at 6 weeks. However,
      G-CSF therapy was associated with a lower ejection fraction at 6 months relative
      to placebo (40.8% [95% CI 37.4%-44.2%] v. 46.0% [95% CI 42.7%-44.3%]). Both
      groups had improved left ventricular function, but change in left ventricular
      ejection fraction was lower in patients treated with G-CSF than in those who
      received placebo (5.7 [95% CI 3.4-8.1] percentage points v. 9.2 [95% CI 6.3-12.1]
      percentage points). One or more of a composite of several major adverse cardiac
      events occurred in 8 patients (19%) within each group, with similar rates of
      target-vessel revascularization. INTERPRETATION: In patients with moderate left
      ventricular dysfunction following anterior-wall infarction, G-CSF therapy was
      associated with a lower 6-month left ventricular ejection fraction but no
      increased risk of major adverse cardiac events. Future studies of G-CSF in
      patients with left ventricular dysfunction should be monitored closely for
      safety. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00394498.

PMID- 24934894
TI  - Ensuring equitable access to sick leave.

PMID- 24934897
TI  - Prioritizing continuity in Canadian clinical teaching units.

PMID- 24934898
TI  - Supreme Court date set for weed growers.

PMID- 24934895
TI  - Management of Bell palsy: clinical practice guideline.

PMID- 24934900
TI  - Nitrogen-fixation catalyst based on graphene: every part counts.
AB  - The catalytic profile and function of each component of a molybdenum-graphene
      based catalyst (Mo/N-doped graphene) for nitrogen fixation, which combines the
      merits of these two components, is evaluated computationally. The Mo/N part acts
      as an active centre for N2 bond breaking and the graphene part works as an
      electron transmitter and electron reservoir. 

PMID- 24934899
TI  - Induced regulatory T cells in inhibitory microenvironments created by cancer.
AB  - INTRODUCTION: Regulatory T cells (Tregs) accumulating in the peripheral
      circulation and tumor sites of patients contribute to tumor escape from the host
      immune system. Tregs encompass subsets of immune cells with distinct phenotypic
      and functional properties. Whereas natural (n) or thymic-derived (t) Tregs
      regulate responses to self-antigens, inducible (i) or peripheral (p) Tregs
      generated and expanded in regulatory microenvironments control immune responses
      to a broad variety of antigens. AREAS COVERED: Tregs accumulating in the tumor
      microenvironment (TME) are contextually regulated. They acquire phenotypic and
      functional attributes imposed by the inhibitory molecular pathways operating in
      situ. Several molecular pathways active in human cancer are reviewed. The
      pathways may differ from one tumor to another, and environmentally induced Tregs
      may be functionally distinct. Potential therapeutic strategies for selective
      silencing of iTregs are considered in the light of the newly acquired
      understanding of their phenotypic and functional diversity. EXPERT OPINION: Human
      Tregs accumulating in cancer comprise 'bad' subsets, which inhibit antitumor
      immunity, and 'good' anti-inflammatory subsets, which maintain tolerance to self
      and benefit the host. Future therapeutic strategies targeting Tregs will need to
      discriminate between these Treg subsets and will need to consider reprogramming
      strategies instead of Treg elimination. Re-establishment of effective antitumor
      immune responses in cancer patients without disturbing a normal homeostatic T
      cell balance will greatly benefit from insights into inhibitory pathways engaged
      by human tumors.

PMID- 24934902
TI  - Identification of the translational start site of codon-optimized mCherry in
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Fluorescent proteins are used widely as reporter genes in many
      organisms. We previously codon-optimized mCherry for Mycobacterium tuberculosis
      and generated expression constructs with high level expression in mycobacteria
      with multiple uses in vitro and in vivo. However, little is known about the
      expression of fluorescent proteins in mycobacteria and the translational start
      codon for mCherry has not been experimentally determined. RESULTS: We determined
      the translational start site for functional (fluorescent) mCherry in
      mycobacteria. Several potential translational start codons were identified;
      introduction of downstream stop codons by mutagenesis was used to determine which
      start codon was utilized in the bacterial cells. Fluorescent protein was
      expressed from a construct which would allow translation of a protein of 226
      amino acids or a protein of 235 amino acids. No fluorescence was seen when a
      construct which could give rise to a protein of 219 amino acids was used. Similar
      results were obtained in mycobacteria and in Escherichia coli. Western blotting
      confirmed that mCherry was expressed from the constructs encoding 235 or 226
      amino acids, but not from the plasmid encoding 219 amino acids. N-terminal
      sequencing and mass determination confirmed that the mature protein was 226 amino
      acids and commenced with the amino acid sequence AIIKE. CONCLUSION: We conclude
      that mCherry is expressed in M. tuberculosis as a smaller protein than expected
      lacking the GFP-derived N-terminal sequence designed to allow efficient fusions.

PMID- 24934901
TI  - Ratiometric measurement of hydrogen sulfide and cysteine/homocysteine ratios
      using a dual-fluorophore fragmentation strategy.
AB  - Hydrogen sulfide (H2S) is an integral signaling molecule in biology with complex
      generation, translocation, and metabolism processes that are intertwined with
      cellular thiols. Differentiating the complex interplay between H2S and biological
      thiols, however, remains challenging due to the difficulty of monitoring H2S and
      thiol levels simultaneously in complex redox environments. As a step toward
      unraveling the complexities of H2S and thiols in sulfur redox homeostasis, we
      present a dual-fluorophore fragmentation strategy that allows for the ratiometric
      determination of relative H2S and cysteine (Cys) or homocysteine (Hcy)
      concentrations, two important metabolites in H2S biosynthesis. The key design
      principle is based on a nitrobenzofurazan-coumarin (NBD-Coum) construct, which
      fragments into spectroscopically differentiable products upon nucleophilic
      aromatic substitution with either H2S or Cys/Hcy. Measurement of the ratio of
      fluorescence intensities from coumarin and the NBD-Cys or NBD-Hcy adducts
      generates a sigmoidal response with a dynamic range of 3 orders of magnitude. The
      developed scaffold displays a rapid response (<1 min) and is selective for
      sulfhydryl-containing nucleophiles over other reactive sulfur, oxygen, and
      nitrogen species, including alcohol- and amine-functionalized amino acids,
      polyatomic anionic sulfur species, NO, and HNO. Additionally, NBD-Coum is
      demonstrated to differentiate and report on different oxidative stress stimuli in
      simulated sulfur pools containing H2S, Cys, and cystine. 

PMID- 24934903
TI  - Adverse obstetric and neonatal outcomes in women with severe mental illness: to
      what extent can they be prevented?
AB  - BACKGROUND: Women with schizophrenia and bipolar disorder are at a higher risk of
      obstetric and neonatal complications. The aim of this study was to better
      understand the factors that may influence these adverse outcomes. METHOD: We
      examined obstetric and neonatal outcomes of pregnant women with schizophrenia and
      bipolar disorder and factors possibly influencing these outcomes. A retrospective
      review of the medical history of 112 women with a DSM-IV diagnosis of
      schizophrenia or bipolar disorder was undertaken. Data for controls were
      extracted from the hospital's electronic birth record data. RESULTS: Women with
      schizophrenia and bipolar disorder presented later for their first antenatal
      visit and had higher rates of smoking and illicit drug use than the control
      group. They also had higher rates of pre-eclampsia and gestational diabetes.
      Their infants were less likely to have Apgar scores 8-10 at both 1 and 5minutes
      and were more likely to be admitted to special care/neonatal intensive care
      nursery than the infants of controls. The rate of pre-term birth was
      significantly increased in the women with schizophrenia and bipolar disorder. Pre
      term birth and admission to special care/neonatal intensive care were predicted
      by smoking and illicit drug use. CONCLUSION: These data point to potentially
      modifiable factors as significant contributors to the high rate of adverse
      obstetric and neonatal outcomes in women with mental illness. Comprehensive
      management of women with mental illness prior to, during pregnancy and in the
      postnatal period may have long-term benefits for their offspring.

PMID- 24934904
TI  - The relationship between serum brain-derived neurotrophic factor (BDNF) and
      cardiometabolic indices in schizophrenia.
AB  - Brain derived neurotrophic factor (BDNF), which has been implicated in the
      pathogenesis of schizophrenia, has been recently shown to be involved in the
      regulation of metabolism and energy homeostasis. This study seeks to examine the
      relationship between BDNF, metabolic indices and cardiovascular (CVD) risk in
      patients with schizophrenia. Medical histories, demographic information and
      anthropometric measurements were collected and analyzed from 61 participants with
      schizophrenia. Fasting glucose and lipids were measured in a central laboratory,
      and serum BDNF was analyzed using commercially available enzyme-linked
      immunosorbent assay (ELISA). The 10-year CVD risk for each participant was
      computed using the Framingham risk score (FRS). Linear regressions were performed
      to examine the relationships between serum BDNF with body mass index (BMI), blood
      pressure (BP), triglycerides (TG), total cholesterol, high-density lipoprotein
      cholesterol (HDL-C) and glucose. To examine the relationship between serum BDNF
      and FRS, serum BDNF was categorized into quartiles, and a multiple regression was
      performed. After adjusting for age, gender and current smoking status, diastolic
      BP (dBP) (p=0.045) and TG (p=0.015) were found to be significantly associated
      with serum BDNF. Participants in the highest quartile of serum BDNF had a 3.3
      times increase in FRS over those in the lowest quartile. Our findings support the
      possible regulatory role of BDNF in metabolism and cardiovascular homeostasis
      among patients with schizophrenia similar to that observed among the non-mentally
      ill. Serum BDNF not only present itself as a candidate biomarker of schizophrenia
      but also might be a viable marker of metabolic co-morbidities associated with
      schizophrenia. 

PMID- 24934905
TI  - Lack of insight 3 years after first-episode psychosis: an unchangeable illness
      trait determined from first presentation?
AB  - BACKGROUND: Lack of insight is recognized as a symptom that predisposes the
      individuals with psychosis to noncompliance with the treatment, leading to poorer
      course of illness. This study aimed to explore baseline predictors of
      disturbances on insight at follow-up. METHODS: Three insight dimensions (insight
      of: 'mental illness', 'need for treatment' and 'the social consequences of the
      disorder') were measured with the Scale to Assess Unawareness of Mental Disorder
      (SUMD) in a cohort of 224 first-episode psychosis (FEP) patients at 3-year follow
      up. Subgroups, good vs. poor insight, were compared on baseline clinical,
      neuropsychological, premorbid and sociodemographic characteristics. Regression
      models tested baseline predictors for each insight dimension. RESULTS: At 3-year
      follow-up a high percentage of patients, 45%, 36% and 33% for each dimension,
      were found to remain lacking insight. Poor insight into having an illness was
      predicted by a diagnosis of schizophrenia and poor baseline insight of the social
      consequences; insight into the need for treatment was predicted by adolescent
      adjustment and depression at baseline; and insight into the social consequences
      of the disorder was determined by late adolescent adjustment and baseline insight
      of mental illness. CONCLUSIONS: Our findings support the hypothesis that long
      term insight in psychosis seems to be, to some extent, determined from first
      presentation, showing trait-like properties. A subgroup of 'lacking insight'
      patients, which is characterized by a diagnosis of schizophrenia, lower levels of
      premorbid adjustment and less severe depressive symptoms at baseline might
      benefit from special interventions targeted at enhancing insight from their first
      contact with psychiatric services.

PMID- 24934906
TI  - Novel 3-hydroxypropyl-bonded phase by direct hydrosilylation of allyl alcohol on
      amorphous hydride silica.
AB  - A novel 3-hydroxypropyl (propanol)-bonded silica phase has been prepared by
      hydrosilylation of allyl alcohol on a hydride silica intermediate, in the
      presence of platinum (0)-divinyltetramethyldisiloxane (Karstedt's catalyst). The
      regio-selectivity of this synthetic approach had been correctly predicted by
      previous reports involving octakis(dimethylsiloxy)octasilsesquioxane (Q8 M8 (H) )
      and hydrogen silsesquioxane (T8 H8 ), as molecular analogs of hydride amorphous
      silica. Thus, C-silylation predominated (~94%) over O-silylation, and high
      surface coverages of propanol groups (5 +/- 1 MUmol/m(2) ) were typically
      obtained in this work. The propanol-bonded phase was characterized by
      spectroscopic (infrared (IR) and solid-state NMR on silica microparticles),
      contact angle (on fused-silica wafers) and CE (on fused-silica tubes) techniques.
      CE studies of the migration behavior of pyridine, caffeine, Tris(2,2'
      bipyridine)Ru(II) chloride and lysozyme on propanol-modified capillaries were
      carried out. The adsorption properties of these select silanol-sensitive solutes
      were compared to those on the unmodified and hydride-modified tubes. It was found
      that hydrolysis of the SiH species underlying the immobilized propanol moieties
      leads mainly to strong ion-exchange-based interactions with the basic solutes at
      pH 4, particularly with lysozyme. Interestingly, and in agreement with water
      contact angle and electroosmotic mobility figures, the silanol-probe interactions
      on the buffer-exposed (hydrolyzed) hydride surface are quite different from those
      of the original unmodified tube.

PMID- 24934907
TI  - Diet in the treatment of ADHD in children - a systematic review of the
      literature.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most
      prevalent psychiatric conditions in childhood. Dietary changes have been
      suggested as a way of reducing ADHD symptoms. AIMS: To provide an overview of the
      evidence available on dietary interventions in children with ADHD, a systematic
      review was carried out of all dietary intervention studies in children with ADHD.
      METHODS: Relevant databases were searched in October 2011, with an update search
      in March 2013. The studies included describe diet interventions in children with
      ADHD or equivalent diagnoses measuring possible changes in core ADHD symptoms:
      inattention, hyperactivity and impulsivity. RESULTS: A total of 52 studies were
      identified, some investigating whether ADHD symptoms can improve by avoiding
      certain food elements (20 studies), and some whether certain food elements may
      reduce ADHD symptoms (32 studies). CONCLUSION: Elimination diets and fish oil
      supplementation seem to be the most promising dietary interventions for a
      reduction in ADHD symptoms in children. However, the studies on both treatments
      have shortcomings, and more thorough investigations will be necessary to decide
      whether they are recommendable as part of ADHD treatment.

PMID- 24934909
TI  - The lip in lupus erythematosus.
AB  - Lupus erythematosus (LE) frequently compromises the skin, lips and oral mucosa.
      There is a large body of medical and dental literature about the cutaneous and
      mucosal lesions of LE, but very little has been written specifically about labial
      lupus. The lip has a peculiar anatomical and histological architecture, and LE
      lesions at this site may have some distinct features. This article reviews the
      existing data and adds some new concepts to the issue of labial lupus in all of
      its presentations, comparing such lesions to the well-established
      characterization of cutaneous LE (in acute, subacute and chronic lesions), and
      highlighting some special clinical features that may enable a better diagnosis
      and differential diagnosis of lip diseases. 

PMID- 24934908
TI  - Venom immunotherapy: an updated review.
AB  - Venom immunotherapy (VIT) is the most effective form of specific immunotherapy to
      date. Hitherto, several relevant queries remain unanswered, namely optimal doses,
      duration, and means of assessment. Important progress has been lately made in
      terms of diagnosis by means of component-resolved diagnosis. Moreover, basophil
      activation test results in patients with negative serum immunoglobulin E (IgE)
      and skin prick test confer this technique a promising future, although these
      outcomes shall be considered with caution. This review aims to unravel the
      important advances made on diagnosis, management, and prognosis and also focuses
      on several undetermined aspects of VIT. 

PMID- 24934910
TI  - Johnson square procedure for lentigo maligna and lentigo maligna melanoma.
AB  - BACKGROUND: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) can be
      difficult to manage surgically. Predetermined margins can be inadequate because
      of subclinical spread, or can affect function when margins are adjacent to the
      eye or mouth. AIM: To describe our 5-year experience in Nottingham of using the
      staged square procedure (Johnson square) in excising difficult facial LM and LMM.
      METHODS: The square procedure is a staged technique useful for ill-defined
      lesions and for lesions that have a high recurrence rate due to subclinical
      spread. It uses paraffin wax-embedded peripheral vertical sections for margin
      control, ensuring complete clearance as the surgical margins are usually examined
      at distances of 2-5 mm from the periphery of the lesion. RESULTS: We treated 21
      patients with LM or LMM with the staged square procedure over a 5-year period. Of
      the 21 patients, 10 needed only one stage of surgery, 6 needed two stages, 3
      needed three stages and 2 needed four stages. To date, there has been only one
      recurrence, which was of an extensive lesion that crossed the medial canthus,
      making margin control impossible because of the anatomical limitations.
      CONCLUSIONS: The staged square procedure is an effective treatment for LM and
      LMM. It attempts to conserve tissue while ensuring a higher clearance rate. This
      offers favourable cosmetic outcomes and better prognosis, especially for facial
      LM and LMM.

PMID- 24934911
TI  - How to set up a psychodermatology clinic.
AB  - BACKGROUND: Psychodermatology is a recognized subspecialty, but lack of awareness
      among dermatologists and limitation of resources make the management of these
      patients challenging. Clinicians are often unsure about the practicalities of
      setting up a psychodermatology service. There is confusion about which model is
      best suited to which service, and about the development of a psychodermatology
      multidisciplinary team. AIM: To identify the necessary steps in setting up a
      psychodermatology clinic. METHODS: The study was based on the experience of a UK
      based psychodermatology unit and the recently published standards by the UK
      Psychodermatology Working Party. RESULTS: The type of service provision will
      depend on the type of patients seen in the unit. The core team will be composed
      of a psychodermatologist and a psychologist. Access to a psychiatrist is
      essential if patients present with primary psychiatric conditions or primary
      cutaneous conditions with suicidal or other psychiatric risks. Adequate training
      of the healthcare staff is advised. The premises and time allocation should be
      adequate, and this translates into higher tariffs. Using business care tariffs
      for people with mental health conditions might be more appropriate, as the
      consultations are longer and involve more members of staff; however, the overall
      cost remains lower than if these patients were seen in a general dermatology
      service or in the community. CONCLUSIONS: Psychodermatology services are globally
      limited, and yet the demand for psychodermatology care is high. There is evidence
      that dedicated psychodermatology services are cost-effective. Healthcare
      professionals need to be aware of the steps necessary to establish and maintain
      psychodermatology services.

PMID- 24934912
TI  - Two-year experience of using the measles, mumps and rubella vaccine as
      intralesional immunotherapy for warts.
AB  - BACKGROUND: The currently available treatments for warts, including cryosurgery,
      laser surgery, electrosurgery, and topical keratolytic applications, are often
      very painful and can induce disfiguring scars. Recently, intralesional
      immunotherapy with skin test antigens and vaccines has been shown to be effective
      in the management of warts. AIMS: To evaluate the efficacy of a new intralesional
      immunotherapy for warts, using the measles, mumps and rubella (MMR) vaccine.
      METHODS: A retrospective study was performed, and we enrolled 136 patients with
      various types of warts into the study, which was for a duration of 2 years.
      Patients were treated for a total of six times at 2-week intervals. The treatment
      response was classified as one of three levels, based on reduction in the size
      and number of warts, and patients with complete response (CR) were checked for
      recurrence. Clinical evaluations were carried out using photographs and medical
      records. RESULTS: Over half (51.5%) of patients experienced > 50% reduction in
      the size and number of warts, and 46.7% who had distant warts (in different
      locations) showed good response. Common warts showed significantly higher
      treatment response than other types of warts (P < 0.05). However, other clinical
      variables did not have any effect on efficacy. Almost all the patients reported
      mild pain during the injection, but other side effects were rarely observed. Only
      5.6% of patients who experienced CR had recurrence of warts after 6 months.
      CONCLUSIONS: We suggest that intralesional immunotherapy with MMR vaccine is a
      tolerable and effective method for patients who are sensitive to pain, concerned
      about side effects, or have common warts. Treatment response is improved by
      increasing the number of injections.

PMID- 24934913
TI  - Cases of occupational dermatitis and asthma in beauticians that were reported to
      The Health and Occupation Research (THOR) network from 1996 to 2011.
AB  - BACKGROUND: Beauticians are exposed to many potential allergens in their
      occupation. AIM: To identify the sources of occupational skin and respiratory
      disease reported in beauticians, with an emphasis on acrylate chemicals, and to
      investigate the trends over time. METHODS: We used the Health and Occupation
      Research (THOR) database to identify occupational disease in beauticians between
      1996 and 2011. Trend analysis was carried out to look for any change in the
      allergens reported over this period. RESULTS: In total, 257 cases of contact
      dermatitis (CD) in beauticians were identified, which were associated with 502
      suspected agents. The most frequently cited source of allergic CD was acrylate
      chemicals. The trend analysis showed a small average annual percentage increase
      in work-related CD in beauticians for all agents (1.1%; 95% CI -2.5 to 4.9).
      There was a small decrease in cases in which acrylates were not cited (-1.7%; 95%
      CI -5.9 to 2.7), and a statistically significant increase when acrylates were
      cited (7.4%; 95% CI 0.9 to 14.4). There were 11 cases of occupational asthma.
      CONCLUSION: We found an increase in cases of occupational dermatitis associated
      with acrylates in beauticians over a 15-year period, and describe other causes of
      occupational dermatitis.

PMID- 24934914
TI  - Atypical naevus spilus: detection by in vivo confocal microscopy.
AB  - Naevus spilus (NS) is a naevoid disorder characterized by hyperpigmented macules
      or papules scattered over a cafe-au-lait macule. Such cafe-au-lait macules are
      often present at birth, and the darker pigmented speckles of NS slowly increase
      in number and size over a period of several years. NS can therefore be difficult
      to evaluate clinically for the development of melanoma. In vivo confocal
      microscopy (IVCM) is a novel method that allows examination at cellular
      resolution of cutaneous lesions in vivo. IVCM has been shown to have twice the
      specificity of dermoscopy for the diagnosis of melanoma, with comparable
      sensitivity. It has been shown to be useful in the detection and grading of
      dysplastic naevi, which are recognized precursors of melanoma in some cases. In
      this report, we highlight that IVCM can also be used as a tool complementary to
      dermoscopy to identify areas of dynamic change in clinically and dermoscopically
      equivocal lesions. IVCM may thereby assist in the early detection of melanocytic
      atypia and melanoma arising in NS, in turn leading to excision of melanoma at an
      early stage, which is associated with a favourable outcome. We also outline some
      of the difficulties encountered in confocal microscopy and histology when
      differentiating melanoma from dysplastic naevi. 

PMID- 24934915
TI  - Simplified noncultured autologous cell grafting for the treatment of chronic
      nonhealing ulcers: the six-well plate technique.
AB  - Chronic recalcitrant ulcers are associated with severe morbidity, and there are
      few effective treatment options available. Living skin substitutes are an
      important form of adjuvant therapy to enhance healing of such wounds. We
      investigated a novel, simplified, noncultured, autologous, cell grafting
      procedure, using a six-well plate technique, to treat chronic recalcitrant
      wounds. This was a prospective pilot study that involved harvesting an ultrathin
      split-skin graft from the gluteal region, which was washed, separated and
      prepared in six different wells to obtain an autologous mixture of keratinocytes,
      melanocytes and fibroblasts; this was subsequently applied directly to the wound
      using a hyaluronic acid (HA) matrix. Eight patients with a total of 14 ulcers
      were recruited. The primary endpoint assessed was the percentage of re
      epithelialization of the ulcers. Secondary endpoints included quality of life and
      wound bed indices. At baseline, the median wound surface area was 7.4 cm(2) (mean
      17.6 +/- 23.6 cm(2) , range 0.5-80.0 cm(2) ) with a median duration of 18 months
      (mean 70.2 +/- 95.9, range 3-216 months). The median wound surface area was
      reduced by 74.3%, from 7.4-1.9 cm(2) , at the final visit. Overall, 28.3% of the
      ulcers achieved complete healing, and 71.3% of the ulcers had reduction in wound
      size. Post-graft, there was also improvement in secondary wound bed parameters
      and all quality of life domains of the Cardiff Wound Impact Schedule. These
      results suggest that this noncultured autologous six-well technique might be
      beneficial for treating recalcitrant ulcers.

PMID- 24934916
TI  - Suicide and depression in a patient with psoriasis receiving adalimumab: the role
      of the dermatologist.
AB  - A 53-year-old man took his own life while receiving biological therapy with the
      tumour necrosis factor-alpha inhibitor adalimumab for severe psoriasis. The
      patient had a psychiatric history and a 32-year history of variable unstable
      psoriasis. Reported suicide in patients with psoriasis receiving adalimumab is
      rare (only one other reported case). It is important, however, to recognize the
      effects of skin disease on the mental health of vulnerable patients receiving
      biological agents. Patients will benefit from a more holistic approach that
      includes both dermatological and psychological assessment and treatment. 

PMID- 24934917
TI  - Discordant expression of desmoglein 2 and 3 at the mRNA and protein levels in
      nodular and superficial basal cell carcinoma revealed by immunohistochemistry and
      fluorescent in situ hybridization.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common human cancer. It is
      thought that skewed expression of desmogleins (Dsgs) in BCC may promote
      tumourigenesis. AIM: To comparatively examine expression of Dsg2/Dsg3, using
      fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in BCC
      subtypes. METHODS: In total, 84 frozen sections from patients with various
      clinical or histological subtypes of BCC were analyzed. Expressions of Dsg2/Dsg3
      protein and Dsg2/Dsg3 mRNA were evaluated using IHC and FISH, respectively, in
      BCC nests and BCC-free epidermis, and then quantitatively measured. RESULTS:
      There was loss of correlation between Dsg2 and Dsg3 (IHC) in nodular and
      superficial BCC (nBCC, sBCC), and significant correlation between Dsg2 and Dsg3
      (FISH) in BCC, but not nBCC and sBCC. CONCLUSIONS: Because more prominent
      aberrations of Dsg2/Dsg3 expression were seen at the protein than at the mRNA
      level in BCC, these comparative observations indicate greater importance of
      events at the proteome level than those at the genome level in tumour functional
      compartments. Different Dsg2/Dsg3 expression in sBCC and nBCC might corroborate
      the possibility that sBCC and nBCC are separate conditions. These results may
      contribute to better understanding of the biological behaviour of BCC.

PMID- 24934918
TI  - Raman spectroscopy as an analytical tool for melanoma research.
AB  - BACKGROUND: Raman spectroscopy is an optical noninvasive screening technology
      that generates individual fingerprints of living cells by reflecting their
      molecular constitution. AIM: To discriminate melanoma cells from melanocytes, to
      identify drug-induced melanoma cell death stages (apoptosis, necrosis, autophagy)
      and to assess the susceptibility of melanoma cells to anticancer therapy.
      METHODS: We used Raman spectroscopy on normal and melanoma cells, and on wild
      type (WT) and mutant melanoma cells, to investigate whether the technique could
      distinguish between different types of cells, identify mutations and evaluate
      response to anticancer therapy. RESULTS: Using the multivariate principal
      component analysis of the Raman spectra, melanocytes could be distinguished from
      melanoma cells, and WT melanoma cells could be distinguished from melanoma cells
      with BRAF or NRAS mutations. When we used the apoptosis inducer staurosporine,
      the necrosis inducer 3-bromopyruvate and the autophagy inducer resveratrol to
      induce cell death in SKMEL28 melanoma cells, Raman spectroscopy clearly
      distinguished between these three types of cell death, as confirmed by
      immunoblotting. Finally, the technique could discriminate between different
      melanoma cell lines according to their susceptibility to high-dose ascorbate.
      CONCLUSIONS: Raman spectroscopy is a powerful noninvasive tool to distinguish
      between melanocytes and melanoma cells, to analyze the specific type of cell
      death in melanoma cells, and to predict the susceptibility of melanoma cells to
      anticancer drugs.

PMID- 24934919
TI  - Identification of a novel mutation (p.Ile198Thr) in gene TYR in a Pakistani
      family with nonsyndromic oculocutaneous albinism.
AB  - The TYR gene (MIM #6069333) is located at position 11q14.3 on the human
      chromosome, and encodes tyrosinase, which is expressed in melanocytes and
      controls the biosynthesis of melanin. Most TYR mutations eliminate the activity
      of tyrosinase, preventing melanocytes from producing any melanin throughout life.
      People with this form of albinism have white hair, light-coloured eyes and very
      pale skin. Some mutations in TYR reduce but do not completely eliminate
      tyrosinase activity, and allow some melanin to be produced. We report a Pakistani
      family with four members affected by oculocutaneous albinism (OCA). Blood samples
      were collected from all affected individuals, normal siblings and their parents.
      Genomic DNA was extracted, and sequence analysis of all the coding exons and
      adjacent intronic sequences of TYR was performed, which identified a novel
      missense substitution (p.Ile198Thr). Sequencing of TYR in 90 unrelated healthy
      individuals showed no sequence variant at this location. Our study expands the
      mutational spectrum of OCA1. 

PMID- 24934920
TI  - Nodule on the forehead.

PMID- 24934921
TI  - 'Dumbo' ear.

PMID- 24934922
TI  - Comparison of efficacy and diffusion of three formulations of botulinum toxin
      type A in two patients with forehead hyperhidrosis.

PMID- 24934923
TI  - Examining the influence of antenatal care visits and skilled delivery on neonatal
      deaths in Ghana.
AB  - BACKGROUND: Many Sub-Saharan African countries may not achieve the Millennium
      Development goal of reducing child mortality by 2015 partly due to the stalled
      reduction in neonatal deaths, which constitute about 60% of infant deaths.
      Although many studies have emphasized the importance of accessible maternal
      healthcare as a means of reducing maternal and child mortality, very few of these
      studies have explored the affordability and accessibility concerns of maternal
      healthcare on neonatal mortality. OBJECTIVE: This study bridges this research gap
      as it aims to investigate whether the number of antenatal visits and skilled
      delivery are associated with the risk of neonatal deaths in Ghana. METHODS: Using
      individual level data of women in their reproductive years from the 2008
      Demographic and Health Survey, the study employs an instrumental variable
      strategy to deal with the potential endogeneity of antenatal care visits.
      RESULTS: Estimates from the instrumental variable estimation show that antenatal
      care visits reduce the risk of neonatal death by about 2%, while older women have
      an approximately 0.2% higher risk of losing their neonates than do younger women.
      CONCLUSION: Findings suggest that women who attend antenatal visits have a
      significantly lower probability of losing their babies in the first month of
      life. Further, results show that women's age significantly affects the risk of
      losing their babies in the neonatal stage. However, the study finds no
      significant effect of skilled delivery and education on neonatal mortality.

PMID- 24934924
TI  - Are the UK systems of innovation and evaluation of medical devices compatible?
      The role of NICE's Medical Technologies Evaluation Programme (MTEP).
AB  - The economic evaluation of medical products and services is increasingly
      prioritised by healthcare decision makers and plays a key role in informing
      funding allocation decisions. It is well known that there are a number of
      methodological difficulties in the health technology assessment of medical
      devices, particularly in the provision of efficacy evidence. By contrasting
      devices with pharmaceuticals, the way in which the differing systems of
      innovation mould the UK's industry landscape is described and substantiated with
      market statistics. In recognition of the challenges faced by industry, as well as
      the growing need for cost-effective allocation of National Health Service (NHS)
      resources, the National Institute for Health and Care Excellence (NICE) led the
      development of the Medical Technologies Evaluation Programme (MTEP), which
      launched in 2009/2010. The review of the UK's medical devices market supports the
      programme's three principal aims: to simplify access to evaluation, speed up the
      process, and increase evaluative capacity for devices within NICE. However, an
      analysis of the output of MTEP's first 3 years suggests that it has some way to
      go to meet each of these aims. 

PMID- 24934925
TI  - Obesity and oxidative stress: potential roles of melatonin as antioxidant and
      metabolic regulator.
AB  - Obesity is associated with an oxidative stress status, defined as an excessive
      production of reactive oxygen species (ROS) compared to the level of antioxidants
      acting in the natural defence systems. Several sources of ROS can be identified
      in obesity (e.g., mitochondrial respiratory chain, or NADPH oxidase) and could
      contribute to the pathogenesis of obesity. Indeed, these conditions favour the
      development of insulin resistance and metabolic syndrome through deregulation of
      adipokines and pro-inflammatory cytokines, so that it could be of interest to
      associate antioxidant therapeutic strategies with strategies of weight loss.
      Among antioxidants, melatonin holds a special place, on the one hand for its
      antioxidant and anti-inflammatory properties, and on the other hand for its role
      as a metabolic regulator. As melatonin modulates several processes involved in
      obesity and its related metabolic alterations, it could have a therapeutic
      interest in the treatment of obesity. 

PMID- 24934926
TI  - The effect of knee extensor open kinetic chain resistance training in the ACL
      injured knee.
AB  - PURPOSE: To investigate the effect of different loads of knee extensor open
      kinetic chain resistance training on anterior knee laxity and function in the ACL
      injured (ACLI) knee. METHODS: Fifty-eight ACLI subjects were randomised to one of
      three (12-week duration) training groups. The STAND group trained according to a
      standardised rehabilitation protocol. Subjects in the LOW and HIGH group trained
      as did the STAND group but with the addition of seated knee extensor open kinetic
      chain resistance training at loads of 2 sets of 20 repetition maximum (RM) and 20
      sets of 2RM, respectively. Anterior knee laxity and measurements of physical and
      subjective function were performed at baseline, 6 and 12 weeks. Thirty-six
      subjects were tested at both baseline and 12 weeks (STAND n = 13, LOW n = 11,
      HIGH n = 12). RESULTS: The LOW group demonstrated a reduction in 133 N anterior
      knee laxity between baseline and 12 weeks testing when compared to the HIGH and
      the STAND groups (p = 0.009). Specifically, the trained-untrained knee laxity
      decreased an average of approximately 5 mm in the LOW group while remaining the
      same in the other two groups. CONCLUSION: Twelve weeks of knee extensor open
      kinetic chain resistance training at loads of 2 sets of 20RM led to a reduction
      in anterior knee laxity in the ACLI knee. This reduction in laxity does not
      appear to offer any significant short-term functional advantages when compared to
      a standard rehabilitation protocol. These results indicate that knee laxity can
      be decreased with resistance training of the thigh muscles. LEVEL OF EVIDENCE:
      Randomised controlled trial, Level II.

PMID- 24934927
TI  - Symmetry of squatting and the effect of fatigue following anterior cruciate
      ligament reconstruction.
AB  - PURPOSE: To evaluate weight-bearing and joint symmetry during the double-leg
      squat exercise at baseline and after fatigue in patients who have undergone
      anterior cruciate ligament reconstruction (ACLR) compared to uninjured controls.
      METHODS: Ten males who had returned to sport after primary ACLR participated
      along with ten uninjured male controls. Lower limb kinematic, kinetic and ground
      reaction force (GRF) data were collected during double-leg squats at baseline and
      after a generalised fatigue protocol. Symmetry indices were calculated for hip
      and knee external flexion moments and the vertical GRF (weight-bearing symmetry)
      at maximum squat depth. These were compared between ACLR and control groups
      before and after fatigue using ANOVA models. RESULTS: The ACL group
      preferentially unloaded the reconstructed limb at baseline, but changed to a more
      symmetrical load distribution to perform the squat exercise in the fatigue
      condition. This same loading pattern was seen at both the knee and hip joints.
      The control group did not show any effect of fatigue. For both groups, symmetry
      indices were closer to zero (which indicated perfect symmetry) in the fatigue
      condition. CONCLUSIONS: When prescribing squat exercises, it should be recognised
      that initially, patients with ACLR tend to unload the affected knee. More
      symmetrical loading patterns may be achieved by inducing bilateral fatigue. When
      fatigued, loading symmetry was similar between this patient group and controls.
      This is relevant information for those who implement rehabilitation training
      programmes. LEVEL OF EVIDENCE: III.

PMID- 24934928
TI  - Radiographic landmarks for surgical reconstruction of the anterolateral ligament
      of the knee.
AB  - PURPOSE: To determine the radiographic landmarks of the anterolateral ligament
      (ALL) on the femur and tibia to assist in intraoperative graft placement during
      ALL reconstruction. METHODS: The footprints of the ALL, fibular collateral
      ligament (FCL), popliteus insertion, lateral gastrocnemius insertion, and Gerdy's
      tubercle were isolated and centrally marked with tantalum beads in thirteen fresh
      frozen cadaveric knees. Measurements were taken from the true lateral
      fluoroscopic images. On the femur, the mean distances from the ALL origin to the
      FCL origin and from the ALL origin to the popliteus insertion were measured. On
      the tibia, the mean distances from the ALL insertion to Gerdy's tubercle and from
      the ALL insertion to the lateral tibial plateau were measured. Furthermore,
      radiographic descriptions of the ALL origin and insertion were developed.
      RESULTS: The ALL origin on the femur averaged 3.3 +/- 1.5 mm anterior-distal to
      the FCL origin in one anatomical variant and 5.4 +/- 1.4 mm posterior-proximal to
      the FCL origin in a second variant. The ALL origin was 9.9 +/- 2.7 mm from the
      popliteus insertion. The ALL origin is described as overlying the posterior
      femoral cortical line, between Blumensaat's line and a line from the posterior
      condylar articular edge parallel to Blumensaat's line. The ALL insertion on the
      tibia averaged 24.7 +/- 4.5 mm posterior to Gerdy's tubercle and 11.5 +/- 2.9 mm
      distal to the lateral tibial plateau. The tibial ALL insertion is described
      between the posterior tibial cortical line and a parallel line drawn down from
      the apex of the tibial spine, and overlying a line drawn perpendicular to the
      posterior tibial cortical line starting from the apex of the posterior tibial
      condyles. CONCLUSIONS: Using direct lateral fluoroscopy, radiographic landmarks
      of the ALL origin and insertion have been described.

PMID- 24934929
TI  - A psychological injury prevention group intervention in Swedish floorball.
AB  - PURPOSE: The main purpose of the study was to evaluate a psychological skills
      training intervention at group level aiming to prevent injuries, separated in
      traumatic and overuse, in male and female elite floorball players. METHODS:
      Twenty-three teams in the premiere leagues for males and females were
      volunteered, and the teams were allocated to an intervention group (n = 11, males
      n = 94, females n = 99) and a control group (n = 12, males n = 109, females n =
      99). The teams in the intervention group participated in a psychological skills
      training programme consisting of six meetings with each team. The control group
      received no substitute. All injuries were registered and documented according to
      the time-loss definition and classified into either traumatic or overuse.
      RESULTS: In total, 142 players (35 %) out of the 401 players sustained 197
      injuries, 0.49 injury/player: in the intervention group 0.45 injury/player and in
      the control group 0.53 injury/player. The analyses revealed no significant
      differences in injuries between intervention groups and control groups. The
      effect size of the influence of the psychological skills training in overuse
      injuries was considered to be small, Cohen's d 0.2. CONCLUSIONS: This study
      comprised the whole team for a group intervention and did not screen for at-risk
      athletes, e.g. scoring high in anxiety or low in coping skills, which might have
      influenced the result. A psychological injury prevention intervention forward to
      a whole team might not influence the injury occurrence significantly. Thus, this
      psychological intervention decreased the injury incidence which is of clinical
      interest. LEVEL OF INCIDENCE: Level II.

PMID- 24934931
TI  - One-pot native chemical ligation of peptide hydrazides enables total synthesis of
      modified histones.
AB  - One of the rising demands in the field of protein chemical synthesis is the
      development of facile strategies that yield the protein in workable quantities
      and homogeneity, with fewer handling steps. Although the native chemical ligation
      of peptide hydrazides has recently been shown to be useful for the chemical
      synthesis of proteins carrying acid-sensitive modification groups, previous
      hydrazide-based protein synthesis studies have used sequential ligation
      strategies. Here, we report a practical method for a "one-pot" native chemical
      ligation of peptide hydrazides that would circumvent the need for the isolation
      of the intermediate products. This method employed a fast and selective
      arylboronate oxidation reaction mediated by H2O2, which draws attention to the
      potential applications of the thus far under-exploited boron-based
      functionalities in protein chemical synthesis. To demonstrate the practicality
      and efficiency of the new one-pot method, we report its application to a scalable
      total synthesis of modified histones (with five analogues of H3 and H4 as
      examples) on a multi-milligram scale, with good homogeneity. 

PMID- 24934930
TI  - Aortic 4D flow: quantification of signal-to-noise ratio as a function of field
      strength and contrast enhancement for 1.5T, 3T, and 7T.
AB  - PURPOSE: To investigate for the first time the feasibility of aortic four
      dimensional (4D) flow at 7T, both contrast enhanced (CE) and non-CE. To quantify
      the signal-to-noise ratio (SNR) in aortic 4D flow as a function of field strength
      and CE with gadobenate dimeglumine (MultiHance). METHODS: Six healthy male
      volunteers were scanned at 1.5T, 3T, and 7T with both non-CE and CE acquisitions.
      Temporal SNR was calculated. Flip angle optimization for CE 4D flow was carried
      out using Bloch simulations that were validated against in vivo measurements.
      RESULTS: The 7T provided 2.2 times the SNR of 3T while 3T provided 1.7 times the
      SNR of 1.5T in non-CE acquisitions in the descending aorta. The SNR gains
      achieved by CE were 1.8-fold at 1.5T, 1.7-fold at 3T, and 1.4-fold at 7T,
      respectively. CONCLUSION: The 7T provides a new tool to explore aortic 4D flow,
      yielding higher SNR that can be used to push the boundaries of acceleration and
      resolution. Field strength and contrast enhancement at all fields provide
      significant improvements in SNR.

PMID- 24934932
TI  - Superconducting properties of (Ba-K)Fe2As2 single crystals disordered with fast
      neutron irradiation.
AB  - Resistivity rho(T), Hall coefficient RH(T), superconducting transition
      temperature Tc and slopes of the upper critical field dHc2/dT were studied in
      (Ba1-xKx)Fe2As2 (x = 0.218, 0.356, 0.531) single crystals irradiated with fast
      neutrons. It is found that dTc/drhoSC-the rate of decreasing Tc as a function of
      the rhoSC (rhoSC is the resistivity at T = Tc)-linearly increases with
      concentration x. Slow changes in the Hall coefficient RH, as well as the
      quadratic electronic contribution to the resistivity, show that there are no
      substantial changes in the topology of the Fermi surface caused by irradiation.
      The slopes of the upper critical field dHc2/dT in ab and c directions as a
      function of rhoSC determined by Hall measurements show a reasonable agreement
      with a model that suggests constancy of the band parameters. 

PMID- 24934934
TI  - The binder effect on an oxide-based anode in lithium and sodium-ion battery
      applications: the fastest way to ultrahigh performance.
AB  - A positive effect of the polyacrylic acid (PAA)-carboxymethyl cellulose (CMC)
      binder to enhance the performance of an oxide-based anode was reported in
      batteries. A series of super high capacity and cycling ability oxide powders
      rarely achieved before was obtained, particularly most of them without any
      specific carbon modification and/or morphology control. 

PMID- 24934933
TI  - Selective activity of the histone deacetylase inhibitor AR-42 against leukemia
      stem cells: a novel potential strategy in acute myelogenous leukemia.
AB  - Most patients with acute myelogenous leukemia (AML) relapse and die of their
      disease. Increasing evidence indicates that AML relapse is driven by the
      inability to eradicate leukemia stem cells (LSC). Thus, it is imperative to
      identify novel therapies that can ablate LSCs. Using an in silico gene expression
      based screen for compounds evoking transcriptional effects similar to the
      previously described anti-LSC agent parthenolide, we identified AR-42 (OSU
      HDAC42), a novel histone deacetylase inhibitor that is structurally similar to
      phenylbutyrate, but with improved activity at submicromolar concentrations. Here,
      we report that AR-42 induces NF-kappaB inhibition, disrupts the ability of Hsp90
      to stabilize its oncogenic clients, and causes potent and specific cell death of
      LSCs but not normal hematopoietic stem and progenitor cells. Unlike parthenolide,
      the caspase-dependent apoptosis caused by AR-42 occurs without activation of Nrf
      2-driven cytoprotective pathways. As AR-42 is already being tested in early
      clinical trials, we expect that our results can be extended to the clinic.

PMID- 24934936
TI  - Medical faculty opinions of peer tutoring.
AB  - CONTEXT AND OBJECTIVES: Peer tutoring is a well-researched and established method
      of learning defined as 'a medical student facilitating the learning of another
      medical student'. While it has been adopted in many medical schools, other
      schools may be reluctant to embrace this approach. The attitude of the teaching
      staff, responsible for organizing and or teaching students in an undergraduate
      medical course to formal peer teaching will affect how it is introduced and
      operationalized. This study elicits faculty opinions on how best to introduce
      peer tutoring for medical students. METHODS: Structured telephone interviews were
      recorded, transcribed and analyzed using thematic analysis. The interviews were
      with medically qualified staff responsible for organizing or teaching
      undergraduate medical students at a New Zealand medical school. Six questions
      were posed regarding perceived advantages and disadvantages of peer tutoring and
      how the school and staff could support a peer-tutoring scheme if one was
      introduced. FINDINGS: Staff generally supported the peer tutoring concept,
      offering a safe environment for learning with its teachers being so close in
      career stage to the learners. They also say disadvantages when the student
      teachers imparted wrong information and when schools used peer tutoring to
      justify a reduction in teaching staff. Subjects felt that faculty would be more
      accepting of peer tutoring if efforts were made to build staff 'buy in' and
      empowerment, train peer tutors and introduce a solid evaluation process.
      CONCLUSIONS: Staff of our school expressed some concerns about peer tutoring that
      are not supported in the literature, signaling a need for better communication
      about the benefits and disadvantages of peer tutoring.

PMID- 24934937
TI  - Superficial and deep learning approaches among medical students in an
      interdisciplinary integrated curriculum.
AB  - INTRODUCTION: Students' learning approaches have a significant impact on the
      success of the educational experience, and a mismatch between instructional
      methods and the learning approach is very likely to create an obstacle to
      learning. Educational institutes' understanding of students' learning approaches
      allows those institutes to introduce changes in their curriculum content,
      instructional format, and assessment methods that will allow students to adopt
      deep learning techniques and critical thinking. The objective of this study was
      to determine and compare learning approaches among medical students following an
      interdisciplinary integrated curriculum. METHODS: This was a cross-sectional
      study in which an electronic questionnaire using the Biggs two-factor Study
      Process Questionnaire (SPQ) with 20 questions was administered. RESULTS: Of a
      total of 402 students at the medical school, 214 (53.2%) completed the
      questionnaire. There was a significant difference in the mean score of
      superficial approach, motive and strategy between students in the six medical
      school years. However, no significant difference was observed in the mean score
      of deep approach, motive and strategy. The mean score for years 1 and 2 showed a
      significantly higher surface approach, surface motive and surface strategy when
      compared with students in years 4-6 in medical school. DISCUSSION: The
      superficial approach to learning was mostly preferred among first and second year
      medical students, and the least preferred among students in the final clinical
      years. These results may be useful in creating future teaching, learning and
      assessment strategies aiming to enhance a deep learning approach among medical
      students. Future studies are needed to investigate the reason for the preferred
      superficial approach among medical students in their early years of study.

PMID- 24934938
TI  - Students perceive healthcare as a valuable learning environment when accepted as
      a part of the workplace community.
AB  - BACKGROUND: The healthcare system is complex and the education of medical and
      nursing students is not always a priority within it. However, education offered
      at the point of care provides students with opportunities to apply knowledge, and
      to develop the necessary skills and attitudes needed to practice their future
      profession. The major objective of this study was to identify students' views of
      generic aspects of the healthcare environment that influences their progress
      towards professional competence. METHODS: We collected free text answers of 75
      medical students and 23 nursing students who had completed an extensive
      questionnaire concerning their learning in clinical wards. In order to obtain
      richer data and a deeper understanding, we also interviewed a purposive sample of
      students. Qualitative content analysis was conducted. RESULTS: We identified
      three themes: (1) How management, planning and organising for learning enabled
      content and learning activities to relate to the syllabus and workplace, and how
      this management influenced space and resources for supervision and learning; (2)
      Workplace culture elucidated how hierarchies and communication affected student
      learning and influenced their professional development and (3) Learning a
      profession illustrated the importance of supervisors' approaches to students,
      their enthusiasm and ability to build relationships, and their feedback to
      students on performance. DISCUSSION: From a student perspective, a valuable
      learning environment is characterised as one where management, planning and
      organising are aligned and support learning. Students experience a professional
      growth when the community of practice accepts them, and competent and
      enthusiastic supervisors give them opportunities to interact with patients and to
      develop their own responsibilities.

PMID- 24934939
TI  - Body expression skills training in a communication course for dental students.
AB  - BACKGROUND: In the health professions, competency in communication skills is
      necessary for the development of a satisfactory physician-patient interaction.
      Body expression is an important domain of the communication process, often not
      adequately addressed. The aim of this study was to describe the methodology and
      content of a pilot introductory training session in body expression for dental
      students before the beginning of their clinical training. METHODS: The
      educational methods were based on experiential learning and embodied training,
      where the session's content focused on five themes representing different phases
      of the dental treatment session. A questionnaire was distributed before and after
      the session to assess any changes in students' self-perceptions in communication
      skills. RESULTS: There were statistically significant improvements in the total
      values of the students self-perceptions of their communication skills obtained
      before and after the training and in specific elements such as small group
      situations, performing an interview, understanding the feelings of others and
      expressing one's own feelings. DISCUSSION: The dental students in the present
      study felt that this preclinical experiential learning session improved their
      communication skills. The feedback from this training experience will enable
      further development of an effective communication course for clinical dentistry.

PMID- 24934940
TI  - Exploring the trustworthiness and reliability of focus groups for obtaining
      useful feedback for evaluation of academic programs.
AB  - BACKGROUND: At Shifa College of Medicine, evaluation is an integral part of the
      curriculum. We used focus groups as a tool to obtain in-depth information
      regarding students' experience with the new integrated, system- based curriculum.
      The purpose of this study was to explore the usefulness of focus groups in
      identifying important issues for curriculum improvement and to explore the
      trustworthiness and representativeness of data obtained through this strategy.
      METHODS: In 2012, we used focus groups to seek feedback from students regarding
      their experience with the integrated curriculum. One course of each of the three
      preclinical years was selected for this purpose. Three parallel focus groups were
      conducted for each selected course. Each focus group was audio recorded, and the
      moderator and a volunteer student took additional notes during the session. The
      audio recordings were transcribed and data obtained from the three sources were
      analyzed, coded, and categorized independently by three investigators. Both
      manifest and latent themes were identified, using an inductive approach. Final
      agreement on themes was reached by comparison of the independently done thematic
      analysis by the three researchers. Reliability of data was established by
      comparing responses from the three parallel focus groups of each course.
      Trustworthiness of inferences was ensured by multiple coding, audit trail and
      member checking with focus group participants who reviewed the themes for
      validity. RESULTS: Most of the data on students' perceptions of their courses
      from each of the parallel groups were in agreement: Similar themes were seen
      within groups of the same class as well as across the three preclinical years.
      CONCLUSION: Focus groups can be a useful tool for collecting trustworthy and
      reliable information through a process that promotes interaction among student
      participants. They can support quantitative data from students and be used to
      support curriculum reform.

PMID- 24934941
TI  - Pilot undergraduate course teaches students about chronic illness in children: an
      educational intervention study.
AB  - BACKGROUND: Recent data question whether medical education adequately prepares
      physicians to care for the growing number of children with chronic medical
      conditions. We describe a 10-week course designed to provide undergraduate
      students with the knowledge and skills required to understand and care for
      children with chronic or catastrophic illnesses. The course presented the illness
      experience from the child's perspective and thus presented information in a
      manner that was efficient, conducive, and memorable. The curriculum was designed
      like a graduate-level seminar that included workshops, lectures, readings,
      writing, and lively discussions. METHODS: This is an educational intervention
      study that used survey data to assess changes in attitudes among and between
      participants completing this course versus students not exposed to this course.
      We used Somers' D test and Fisher's z-transformation to perform both pre- and
      post-nonparametric comparisons. RESULTS: Course participants were more likely to
      change their attitudes and agree that chronically ill children "feel comfortable
      talking with their peers about their condition" (P=0.003) and less likely to
      agree that these children "want to be treated differently," "want more sympathy,"
      or "care less about romantic relationships" (P = 0.003, 0.002 and 0.02,
      respectively). Controls were more likely to continue to agree that chronically
      ill children "want to be treated differently" (P = 0.009) and "care less about
      romantic relationships" (P = 0.02), and less likely to agree that these children
      "talk openly" or "feel comfortable talking with their peers about their
      condition" (P = 0.04). CONCLUSIONS: This classroom-based course serves as a
      feasible and cost-effective model for universities and medical schools to aid in
      improving student attitudes toward treating chronically ill children. The course
      provides the unique opportunity to learn directly from those who care for and
      those who have lived with chronic illness.

PMID- 24934942
TI  - Trust, continuity and agency: keys to understanding older patients' attitudes to
      general practice trainees.
AB  - BACKGROUND: Populations are ageing and therefore non-communicable diseases are
      becoming leading causes of global morbidity, which need to be the focus of
      primary care services and training. Some older patients are uncomfortable with
      general practitioner (GP) trainees managing their chronic conditions, reducing
      clinical experience opportunities for trainees. This Australian cross-sectional
      study explored the factors underlying patients' attitudes to trainees in an
      agency theory framework. METHODS: Fifty patients aged 60 and over from each of 38
      training practices were offered a questionnaire after their consultation.
      Principal component analysis of the results was undertaken. Factor scores were
      calculated. Binary logistic modelling was used to identify relationships between
      participant characteristics, behaviours, attitude items and factor scores.
      RESULTS: The response rate was 47.9% (n = 911). Three factors were identified:
      'Interpersonal Trust' (IPT); 'Institution/system Trust' (ST); and 'Interpersonal
      Continuity' (IPC). Lower self-rated health (SRH) was associated with higher IPT
      factor scores (P = 0.023); higher SRH with higher ST scores (P = 0.001); and
      chronic illness with higher IPC scores (P = 0.005). Higher ST scores were
      associated with greater comfort with trainees' involvement in chronic care (P <
      0.001) and frequency of trainee visits (P < 0.001), while higher IPC scores were
      negatively associated (P < 0.001 and P = 0.003, respectively). High IPT scores
      were associated with lower satisfaction with trainee visits (P = 0.001).
      DISCUSSION: These results indicate that better SRH, via higher institution/ST, is
      associated with favourable attitudes and attendance with trainees. In addition,
      chronic illness, via a higher need for IPC, is associated with lower comfort and
      attendance. These findings are consistent with agency theory, which shows
      potential as a framework for future interventions and research into older patient
      trainee interactions.

PMID- 24934943
TI  - Community-based medical education: is success a result of meaningful personal
      learning experiences?
AB  - BACKGROUND: Community-based medical education (CBME) is the delivery of medical
      education in a specific social context. Learners become a part of social and
      medical communities where their learning occurs. Longitudinal integrated
      clerkships (LICs) are year-long community-based placements where the curriculum
      and clinical experience is typically delivered by primary care physicians. These
      programs have proven to be robust learning environments, where learners develop
      strong communication skills and excellent clinical reasoning. To date, no
      learning model has been offered to describe CBME. METHODS: The characteristics of
      CBME are explored by the authors who suggest that the social and professional
      context provided in small communities enhances medical education. The authors
      postulate that meaningfulness is engendered by the authentic context, which
      develops over time. These relationships with preceptors, patients and the
      community provide meaningfulness, which in turn enhances learning. RESULTS AND
      DISCUSSION: The authors develop a novel learning model. They propose that the
      context-rich environment of CBME allows for meaningful relationships and
      experiences for students and that such meaningfulness enhances learning.

PMID- 24934944
TI  - A study of obstetricians' knowledge, attitudes and practices in oral health and
      pregnancy.
AB  - BACKGROUND: Many studies have reported an association between periodontitis and
      adverse pregnancy outcomes, but there has been little research on the knowledge
      of obstetricians regarding oral care. The aim of the study was to assess the
      knowledge and attitudes of practicing obstetricians in India about the
      relationship between oral health and pregnancy outcomes, as well as their
      practice behaviors regarding oral healthcare in pregnant women in Indian
      settings. METHODS: A structured online questionnaire was sent to 130
      obstetricians in the city of Chandigarh and adjoining areas of the union
      territory. The questionnaire was prepared by dentists and obstetricians and was
      validated in a prior pilot study. Obstetricians' knowledge of the effects of
      pregnancy on oral health, and vice versa, were correlated with their experience
      and practices. RESULTS: A total of 79.2% responded to the questionnaire. More
      than 70% of respondent obstetricians correctly knew of the effects of
      periodontitis on preterm birth and low birth weight babies. Only 40% recommended
      dental examination during pregnancy and 47% advised patients about oral care
      during pregnancy. There were significant correlations between knowledge of dental
      health effects on pregnancy and referrals of patients to dentists. CONCLUSIONS:
      This study found that although obstetricians generally were knowledgeable about
      appropriate dental care practices during pregnancy as well as the relationship
      between oral health and pregnancy outcomes, this knowledge often did not
      translate into appropriate practice behavior.

PMID- 24934945
TI  - Think global, act local: medical students contextualize global health education.
AB  - BACKGROUND: There is considerable heterogeneity in the extent to which global
      health education is emphasized in undergraduate medical curricula. Here, we
      performed an exploratory analysis to test the hypothesis that exposure to global
      health education may influence the attitudes of medical students toward the
      treatment of local vulnerable patient populations. METHODS: All pre-clerkship
      students at an urban Canadian university were invited to attend a voluntary
      global health education session on challenges in treating human immunodeficiency
      virus (HIV) in the developing world. Those who attended as well as those who did
      not completed pre- and post-session surveys measuring willingness to treat
      patients with HIV and related attitudes. A repeated measure analysis of variance
      (ANOVA) was performed to assess the effect of the intervention on attitudes
      toward locally affected populations. RESULTS: A total of 201 (81.4%) and 143
      (58.3%) students completed the pre- and post-session surveys, respectively.
      Students who scored their willingness to treat patients with HIV within highest
      10% of the scale on the pre-session survey were excluded from the analysis to
      account for a ceiling effect. On repeated measure ANOVA, willingness to treat
      local patients with HIV increased significantly following the session (P < 0.01).
      Students intending to attend the session also reported a greater propensity to
      treat patients with HIV than those who did not (P = 0.03). DISCUSSION: In this
      exploratory study, we find that following exposure to a global health lecture on
      the challenges of HIV in the developing world, students possessed more favorable
      attitudes toward the treatment of marginalized local patient populations, a
      finding that may be exploited in undergraduate and continuing medical education.

PMID- 24934946
TI  - Career intentions of medical students trained in India.

PMID- 24934947
TI  - Is the UK'S situational judgement test a fair and appropriate way to allocate
      jobs to new doctors?

PMID- 24934949
TI  - Student medical journalism: the JPMS experience.

PMID- 24934948
TI  - Paying to publish: Should we?

PMID- 24934950
TI  - Electronic learning in Iran's medical schools; students' need for basic computer
      skills.

PMID- 24934952
TI  - FHI360-SATELLIFE essential health links.

PMID- 24934951
TI  - Constructing hope and peace in Syrian dental education during the country's time
      of difficulty: Success in Syrian smiles.

PMID- 24934953
TI  - Issues, applications and outcomes in interprofessional education.

PMID- 24934954
TI  - Engagement studios: students and communities working to address the determinants
      of health.
AB  - BACKGROUND: This article presents an innovative model for interprofessional
      community-oriented learning. The Engagement Studios model involves a partnership
      between community organizations and students as equal partners in conversations
      and activities aimed at addressing issues of common concern as they relate to the
      social determinants of health. METHODS: Interprofessional teams of students from
      health and non-health disciplines work with community partners to identify
      priority community issues and explore potential solutions. RESULTS: The student
      teams work with a particular community organization, combining their unique
      disciplinary perspectives to develop a project proposal, which addresses the
      community issues that have been jointly identified. Approved proposals receive a
      small budget to implement the project. DISCUSSION: In this paper we present the
      Engagement Studios model and share lessons learned from a pilot of this
      educational initiative.

PMID- 24934955
TI  - Integrating medical and health multiprofessional residency programs: the
      experience in building an interprofessional curriculum for health professionals
      in Brazil.
AB  - BACKGROUND: The aging of the population demands a development of the skills of
      different health professionals working in teams due to the complexity of the
      problems arising from this population. This article discusses the integration of
      two residency programs: medical and multiprofessional. The challenge was to
      construct a curriculum with practical and theoretical activities that develop
      competencies within the scope of interprofessional education, ensuring the
      necessary depth and detail of study in all the professional areas involved in the
      development of specific skills. METHODS: The curricular integration was
      accomplished by conducting workshops with the participation of coordinators from
      both programs and service areas, preceptors of medicine, nursing, nutrition,
      psychology, physiotherapy, and social services. In these workshops, we agreed
      upon the goals, general and specific competencies, the standard weekly schedule,
      practice scenarios, evaluation, and selection. RESULTS: The interprofessional
      program has 26 residents, of which 6 are physicians 4 each from the other areas,
      with 25 preceptors from the 6 areas that comprise the program. The residents
      develop their training in six practical scenarios distributed between the first
      and second years with increasing complexity. DISCUSSION: The program is based on
      guidelines, physical conditions and human resources that allow for the overcoming
      of barriers to the development of interprofessional education and collaborative
      practice.

PMID- 24934956
TI  - Patients' nursing records revealing opportunities for interprofessional workplace
      learning in primary care: a chart review study.
AB  - BACKGROUND: Working and learning go hand in hand during interprofessional
      collaborative practice. Patients' nursing records are designed to record patient
      care and health status. It is not known whether these records are also used to
      keep track of interprofessional contacts or interprofessional learning between
      team members. This study explored the usefulness of patients' nursing records in
      optimising interprofessional workplace learning for general practitioners.
      METHODS: We utilized a descriptive retrospective chart review. All palliative
      home care teams of the Dutch speaking part of Belgium were involved. Throughout
      the year 2010, a representative sample of patient charts was selected.
      Characteristics of encounters between general practitioners and palliative care
      nurses were extracted from the charts. RESULTS: Detailed accounts of
      interprofessional contacts were found in the charts. Palliative care nurses
      recorded number and type of contacts, topics discussed during contacts and
      general practitioner's learning activities. DISCUSSION: Palliative care nurses
      are sensitive and open towards the general practitioners' learning needs.
      Patients' nursing records provide useful information for interprofessional team
      discussions on workplace learning. Healthcare professionals should be trained to
      respond to each other's learning needs.

PMID- 24934957
TI  - The REACH project: implementing interprofessional practice at Australia's first
      student-led clinic.
AB  - BACKGROUND: REACH (Realising Education and Access in Collaborative Health) is an
      initiative of  students of the University of Melbourne to improve access to
      primary health care services. It is driven by the voluntary commitment of over
      120 students and is built upon the principles of collaboration,
      interprofessionalism and client-centered care. Summary of work: The feasibility
      of student-led clinics has been demonstrated with the operation of over 100 such
      clinics in North America. Senior students from Medicine, Physiotherapy, Nursing
      and Social Work attended a student-run clinics conference in Jacksonville,
      Florida, USA in 2010. On return, research was conducted to identify a local
      underserviced community appropriate for a clinic. On review of the literature, it
      was determined an interprofessional model of care would best serve this
      community. The student body engaged a local community health service as a project
      partner. The model of care at the REACH Clinic was developed by senior students
      from the schools of Medicine, Physiotherapy, Nursing and Social Work and managed
      by an interconnected student committee structure. The final consultation model
      involves a triage process and simultaneous consultation by two disciplines. This
      model of care was successfully implemented during a 4-week pilot period in
      October 2011. RESULTS: Several issues were identified during the REACH pilot,
      with dissonance between the at-times competing principles in health care of
      interprofessionalism, client-centered care and efficient care. CONCLUSIONS: An
      interprofessional model of care was developed and successfully implemented in a 4
      week pilot student-run clinic within an established community health service.
      While providing a free health service, this model facilitated interprofessional
      learning at both a clinical and management level and highlighted logistical and
      ideological challenges that served as the basis for further refinement of this
      model of community service .

PMID- 24934958
TI  - Street outreach and shelter care elective for senior health professional
      students: an interprofessional educational model for addressing the needs of
      vulnerable populations.
AB  - BACKGROUND: University of New Mexico Health Sciences Center (UNMHSC), located in
      Albuquerque, New Mexico, USA, has an international reputation for developing and
      implementing curricular initiatives addressing health inequities. The Street
      Outreach and Shelter Care elective is designed to provide interprofessional
      service learning opportunities for senior pharmacy and medical students
      addressing the needs of our nation's most marginalized population-those
      experiencing homelessness. METHODS: Our institution collaborated with multiple
      community partners serving the homeless to develop, implement and teach a 4-week
      senior elective for health professions students. During this elective, senior
      pharmacy and medical student teams provide individualized health care to men in
      local homeless shelter facilities. Students also participate in street outreach
      programs across a continuum of homeless populations. Weekly interprofessional
      education (IPE) faculty-facilitated sessions allow students to reflect on their
      experiences and learn from other discipline perspectives. RESULTS: Student
      evaluations uniformly reflect the transformative nature of the rotation since its
      inception, April 2009. Our outcomes corroborated the findings of similar service
      learning models developed to sensitize health professions students to the complex
      challenges of homeless populations. DISCUSSION: Academic centers can play a
      central role in health education reform by instituting curricula focusing on the
      primacy of population welfare and just distribution of resources. Senior year is
      an opportune time to reinforce social accountability among health professions
      before graduation. This elective is based on adult principles of learning and can
      serve as an international educational model for developing interprofessional
      curricular innovations addressing the healthcare needs of vulnerable populations.

PMID- 24934959
TI  - Community oriented interprofessional health education in Mozambique: one
      student/one family program.
AB  - BACKGROUND: In the remote northern region of Mozambique the ratio of doctors to
      patients is 1:50,000. In 2007, Lurio University initiated an innovative, "One
      Student/One Family" program of teaching and learning for health professions
      students, to complement their traditional core curriculum. All students of each
      of the school's six health degree programs complete a curriculum in "Family and
      Community Health" in each year of their training. METHODS: Groups of six students
      from six different health professions training programs make weekly visits to
      communities, where each student is allocated to a family. Students learn from
      their families about community life and health issues, within a community where
      80% of the population still lacks access to modern health care and rely on
      indigenous doctors and traditional remedies. In turn, students transmit
      information to families about modern health care and report to the faculty any
      major health problems they find. The educational/experiential approach is
      interprofessional and community-oriented. RESULTS: The main perceived advantages
      of the program are that it is applied and problem-based learning for students,
      while simultaneously providing needed healthcare services to the community. The
      major disadvantages include the complexity of coordinating multidisciplinary
      groups, the time and distance required of students in traveling to communities,
      and interpretation of multiple reports with variable data. DISCUSSION: This
      community-oriented education program involving students from six disciplines uses
      nontraditional teaching/learning methods is the basis of the ex libris of Lurio
      University.

PMID- 24934960
TI  - The bacterial lipopeptide iturins induce Verticillium dahliae cell death by
      affecting fungal signalling pathways and mediate plant defence responses involved
      in pathogen-associated molecular pattern-triggered immunity.
AB  - Verticillium wilt in cotton caused by Verticillium dahliae is one of the most
      serious plant diseases worldwide. Because no known fungicides or cotton cultivars
      provide sufficient protection against this pathogen, V. dahliae causes major crop
      yield losses. Here, an isolated cotton endophytic bacterium, designated Bacillus
      amyloliquefaciens 41B-1, exhibited greater than 50% biocontrol efficacy against
      V. dahliae in cotton plants under greenhouse conditions. Through high-performance
      liquid chromatography and mass analysis of the filtrate, we found that the
      antifungal compounds present in the strain 41B-1 culture filtrate were a series
      of isoforms of iturins. The purified iturins suppressed V. dahliae
      microsclerotial germination in the absence or presence of cotton. Treatment with
      the iturins induced reactive oxygen species bursts, Hog1 mitogen-activated
      protein kinase (MAPK) activation and defects in cell wall integrity. The
      oxidative stress response and high-osmolarity glycerol pathway contribute to
      iturins resistance in V. dahliae. In contrast, the Slt2 MAPK pathway may be
      involved in iturins sensitivity in this fungus. In addition to antagonism,
      iturins could induce plant defence responses as activators and mediate pathogen
      associated molecular pattern-triggered immunity. These findings suggest that
      iturins may affect fungal signalling pathways and mediate plant defence responses
      against V. dahliae. 

PMID- 24934961
TI  - Dangers of eating vegetables: contralateral perfusion deficit with an inhaled
      foreign body.

PMID- 24934962
TI  - Combination treatment with varenicline and bupropion in an adaptive smoking
      cessation paradigm.
AB  - OBJECTIVE: The authors assessed the efficacy and safety of combination treatment
      with varenicline and sustained-release bupropion for smokers who, based on an
      assessment of initial smoking reduction prior to the quit date, were deemed
      unlikely to achieve abstinence using nicotine patch treatment. METHOD: In a
      randomized, double-blind, parallel-group adaptive treatment trial, the authors
      identified 222 cigarette smokers who failed to show a reduction of more than 50%
      in smoking after 1 week of nicotine patch treatment. Smokers were randomly
      assigned to receive 12 weeks of varenicline plus bupropion or varenicline plus
      placebo. The primary outcome measure was continuous smoking abstinence at weeks 8
      11 after the target quit date. RESULTS: Both treatments were well tolerated.
      Participants who received the combination treatment had a significantly higher
      abstinence rate than those who received varenicline plus placebo (39.8% compared
      with 25.9%; odds ratio=1.89; 95% CI=1.07, 3.35). Combination treatment had a
      significantly greater effect on abstinence rate in male smokers (odds ratio=4.26;
      95% CI=1.73, 10.49) than in female smokers (odds ratio=0.94; 95% CI=0.43, 2.05).
      It also had a significantly greater effect in highly nicotine-dependent smokers
      (odds ratio=3.51, 95% CI=1.64, 7.51) than in smokers with lower levels of
      dependence (odds ratio=0.71, 95% CI=0.28, 1.80). CONCLUSIONS: Among smokers who
      did not show a sufficient initial response to prequit nicotine patch treatment,
      combination treatment with varenicline and bupropion proved more efficacious than
      varenicline alone for male smokers and for smokers with a high degree of nicotine
      dependence.

PMID- 24934964
TI  - Quantitative estimation of the parameters for self-motion driven by difference in
      surface tension.
AB  - Quantitative information on the parameters associated with self-propelled objects
      would enhance the potential of this research field; for example, finding a
      realistic way to develop a functional self-propelled object and quantitative
      understanding of the mechanism of self-motion. We therefore estimated five main
      parameters, including the driving force, of a camphor boat as a simple self
      propelled object that spontaneously moves on water due to difference in surface
      tension. The experimental results and mathematical model indicated that the
      camphor boat generated a driving force of 4.2 MUN, which corresponds to a
      difference in surface tension of 1.1 mN m(-1). The methods used in this study are
      not restricted to evaluate the parameters of self-motion of a camphor boat, but
      can be applied to other self-propelled objects driven by difference in surface
      tension. Thus, our investigation provides a novel method to quantitatively
      estimate the parameters for self-propelled objects driven by the interfacial
      tension difference. 

PMID- 24934963
TI  - A treatment for severe nodular acne: a randomized investigator-blinded,
      controlled, noninferiority trial comparing fixed-dose adapalene/benzoyl peroxide
      plus doxycycline vs. oral isotretinoin.
AB  - BACKGROUND: Oral isotretinoin (ISO) is the gold standard for severe nodular acne.
      However, as some patients are unwilling or unable to take, or are intolerant to,
      ISO, other options are needed. OBJECTIVES: To compare efficacy and safety of oral
      ISO vs. doxycycline 200 mg plus adapalene 0.1%/benzoyl peroxide 2.5% gel
      (D+A/BPO) in severe nodular acne over 20 weeks. METHODS: This was a multicentre,
      randomized, controlled, noninferiority investigator-blinded study involving 266
      subjects. RESULTS: D+A/BPO showed a significantly earlier onset of action in
      reducing nodules, papules/pustules and total lesions at week 2. ISO was superior
      in reducing nodules (95.6% vs. 88.7%), papules/pustules (95.2% vs. 79.6%) and
      total lesions (92.9% vs. 78.2%; all P < 0.01) at week 20. Half as many subjects
      for D+A/BPO compared with ISO had treatment-related, medically relevant adverse
      events (33 events in 18.0% of subjects vs. 73 in 33.8% of subjects,
      respectively). D+A/BPO was noninferior to ISO in the intent-to-treat population
      [95% confidence interval (CI) -2.7 to 20.8 (P = 0.13); 63.9% vs. 54.9% of
      subjects, respectively] and per-protocol population [95% CI 3.9-28.6 (P = 0.01);
      74.3% vs. 58% of subjects, respectively), based on the composite efficacy/safety
      end point. CONCLUSIONS: D+A/BPO showed a favourable composite efficacy/safety
      profile compared with ISO. This combination is an alternative to ISO in patients
      intolerant to, or unable or unwilling to take, oral ISO, and is an option for
      treatment of severe nodular acne.

PMID- 24934965
TI  - Autophagy: basic principles and relevance to transplant immunity.
AB  - Autophagy developed into a rapidly expanding field detailing its molecular
      mechanism and relevance in health and disease. Autophagy is an evolutionarily
      conserved process that summarizes a pathway in which intracellular material is
      degraded within the lysosome and where the macromolecular constituents are
      recycled. This "self-eating" process was originally described in a cell under
      starvation but now numerous studies established autophagy as a cellular response
      to stress. As a consequence, the autophagy machinery interfaces with most
      cellular stress-response pathways, including those involved in controlling immune
      response and inflammation. Autophagy also influences adaptive immunity through
      its effect on antigen presentation, naive T cell repertoire selection and
      homeostasis and TH cell polarization. Data are emerging that dysregulated
      autophagy has an impact on human pathologies including infectious diseases,
      cancers, aging and neurodegenerative conditions. This review focuses on recent
      findings elucidating the ability of autophagy to be of significance in the
      transplant setting. 

PMID- 24934966
TI  - Cancer research provides a good economic return as well as health gains, report
      says.

PMID- 24934967
TI  - Differential proteomics study of platelets in asymptomatic constitutional
      macrothrombocytopenia: altered levels of cytoskeletal proteins.
AB  - OBJECTIVES: Harris platelet syndrome (HPS), also known as asymptomatic
      constitutional macrothrombocytopenia (ACMT), is an autosomal dominant platelet
      disorder characterized by mild-to-severe thrombocytopenia and giant platelets
      with normal platelet aggregation and absence of bleeding symptoms. We have
      attempted a comparative proteomics study for profiling of platelet proteins in
      healthy vs. pathological states to discover characteristic protein expression
      changes in macrothrombocytes and decipher the factors responsible for the
      functionally active yet morphologically distinct platelets. METHODS: We have used
      2-D gel-based protein separation techniques coupled with MALDI-ToF/ToF-based mass
      spectrometric identification and characterization of the proteins to investigate
      the differential proteome profiling of platelet proteins isolated from the
      peripheral blood samples of patients and normal volunteers. RESULTS AND
      CONCLUSION: Our study revealed altered levels of actin-binding proteins such as
      myosin light chain, coactosin-like protein, actin-related protein 2/3 complex,
      and transgelin2 that hint toward the cytoskeletal changes necessary to maintain
      the structural and functional integrity of macrothrombocytes. We have also
      observed over expressed levels of peroxiredoxin2 that signifies the prevailing
      oxidative stress in these cells. Additionally, altered levels of protein
      disulfide isomerase and transthyretin provide insights into the measures adapted
      by the macrothrombocytes to maintain their normal functional activity. This first
      proteomics study of platelets from ACMT may provide an understanding of the
      structural stability and normal functioning of these platelets in spite of their
      large size.

PMID- 24934968
TI  - Biosynthesis of gold nanoparticles using Sargassum swartzii and its cytotoxicity
      effect on HeLa cells.
AB  - In this investigation, biological synthesis of gold nanoparticles (AuNPs) using
      Sargassum swartzii and its cytotoxicity against human cervical carcinoma (HeLa)
      cells is reported. The biological synthesis involved the reduction of chloroauric
      acid led to the formation of AuNPs within 5min at 60 degrees C and the formation
      of AuNPs was confirmed using UV-vis spectrophotometer. The AuNPs were stable;
      spherical in shape with well-defined dimensions, and the average size of the
      particle is 35nm. A zeta potential value of -27.6mV revealed synthesized AuNPs
      were highly stable. The synthesized AuNPs exhibited a dose-dependent cytotoxicity
      against human cervical carcinoma (HeLa) cells. Furthermore, induction of
      apoptosis was measured by DAPI (4',6-Diamidino-2-phenylindole dihydrochloride)
      staining. 

PMID- 24934969
TI  - Comparative study for determination of some polycyclic aromatic hydrocarbons
      'PAHs' by a new spectrophotometric method and multivariate calibration coupled
      with dispersive liquid-liquid extraction.
AB  - A modified dispersive liquid-liquid extraction (DLLE) procedure coupled with
      spectrophotometric techniques was adopted for simultaneous determination of
      naphthalene, anthracene, benzo(a)pyrene, alpha-naphthol and beta-naphthol in
      water samples. Two different methods were used, partial least-squares (PLS)
      method and a new derivative ratio method, namely extended derivative ratio (EDR).
      A PLS-2 model was established for simultaneous determination of the studied
      pollutants in methanol, by using twenty mixtures as calibration set and five
      mixtures as validation set. Also, in methanol a novel (EDR) method was developed
      for determination of the studied pollutants, where each component in the mixture
      of the five PAHs was determined by using a mixture of the other four components
      as divisor. Chemometric and EDR methods could be also adopted for determination
      of the studied PAH in water samples after transferring them from aqueous medium
      to the organic one by utilizing dispersive liquid-liquid extraction technique,
      where different parameters were investigated using a full factorial design. Both
      methods were compared and the proposed method was validated according to ICH
      guidelines and successfully applied to determine these PAHs simultaneously in
      spiked water samples, where satisfactory results were obtained. All the results
      obtained agreed with those of published methods, where no significant difference
      was observed. 

PMID- 24934970
TI  - Turn-on electrochemiluminescence sensing of Cd(2+) based on CdTe quantum dots.
AB  - A simple and sensitive method for the detection of cadmium ion was proposed based
      on the electrochemiluminescence (ECL) of thioglycolic acid capped-CdTe quantum
      dots (CdTe QDs). The ECL of CdTe QDs was firstly quenched by introduction of
      S(2)(-) and was restored due to following addition of Cd(2+), on the basis of
      which, a "turn-on" ECL method for the detection of Cd(2+) was demonstrated. The
      ECL of CdTe QDs exhibited linear response toward Cd(2+) concentration in the
      range from 6.3nM to 3.4MUM (R=0.999) with a detection limit of 2.1nM. The
      proposed assay was simple, sensitive, selective, and practicable in real water
      samples. 

PMID- 24934972
TI  - Synthesis, characterization and spectroscopic behavior of novel 2-oxo-1,4
      disubstituted-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile dyes.
AB  - Two synthetic pathways were adopted to synthesize the target 2-oxo-1,4
      disubstituted-1,2,5,6-tetrahydro-benzo[h]quinoline-3-carbonitriles. Structure of
      the synthesized compounds has been characterized based on FT-IR, (1)H NMR, (13)C
      NMR and elemental analyses. UV-Vis and fluorescence spectroscopy measurements
      provided that all compounds are good absorbent and fluorescent. Fluorescence
      polarity study demonstrated that these compounds were sensitive to the polarity
      of the microenvironment provided by different solvents. In addition,
      spectroscopic and physicochemical parameters, including singlet absorption,
      extinction coefficient, Stokes shift, oscillator strength and dipole moment were
      investigated in order to explore the analytical potential of synthesized
      compounds. 

PMID- 24934971
TI  - Self-assembly of Terbium(III)-based metal-organic complexes with two-photon
      absorbing active.
AB  - Hybrid complexes based on D-pi-A type dyes p-aminostyryl-pyridinum and
      Terbium(III) complex anion (1, 2) have been synthesized by ionic exchange
      reaction. Meanwhile two different alkyl-substituted amino groups were used as
      electron donors in organic dyes cations. The synthesized complexes were
      characterized by element analysis. In addition, the structural features of them
      were systematic studied by single crystal X-ray diffraction analysis. Their
      linear properties have been systematically investigated by absorption spectra and
      fluorescence, the results show that the energy transfer takes place from the
      trans-4-[4'-(N,N-diethylamino)styryl]-N-methyl pyridinium (2') cation to Tb(III).
      In addition, complex 2 exhibit a large two-photon absorption coefficient beta:
      0.044cm/GW at 710nm. 

PMID- 24934973
TI  - Synthesis and characterization of metal complexes of Schiff base ligand derived
      from imidazole-2-carboxaldehyde and 4-aminoantipyrine.
AB  - The Co(II), Ni(II), Cu(II) and Zn(II) complexes of the Schiff base derived from
      imidazole-2-carboxaldehyde and 4-aminoantipyrine were synthesized. These
      compounds were characterized by elemental analysis, IR, mass, (1)H NMR,
      electronic spectra, magnetic moment, molar conductance, thermal analysis, powder
      XRD and SEM. The analytical data show that the metal to ligand ratio is 1:1. The
      IR results show that the ligand acts as a bidentate donor coordinating through
      the azomethine nitrogen and imidazole nitrogen atoms. From the electronic spectra
      and magnetic moment value predicts the geometry of the complexes. The surface
      morphology of the compounds was studied by SEM. The compounds were screened for
      their antibacterial activity and antifungal activity using Kirby Bayer disc
      diffusion method. The DNA cleavage and superoxide dismutase activities of the
      compounds were investigated. The anticancer activities of the complexes have been
      carried out towards HeLa and HCT116 cancer cells. 

PMID- 24934974
TI  - Detection of perchlorate using Ag/DMAH(+) SERS-active capture matrices.
AB  - In this communication, the fabrication of SERS-active capture matrices for the
      detection of perchlorate is described. The amine groups of amine-modified
      magnetic microparticles were used to immobilize silver colloidal particles. Once
      immobilized, the silver was reacted with dimethylaminoethanethiol hydrochloride
      (DMAH(+)Cl(-)) to form a self-assembled monolayer (SAM). The DMAH(+) SAM exhibits
      reasonably good selectivity for perchlorate. It was shown that calibration curves
      could be generated by ratioing the perchlorate peak with a DMAH(+) peak that did
      not change upon interaction with the perchlorate ion. Flow experiments, using
      Ag/DMAH(+) capture matrices held in place by a magnet, showed instantaneous
      response to changes in perchlorate concentration. The use of solid phase
      extraction (SPE) to eliminate chloride ion interference was explored. 

PMID- 24934975
TI  - FT-IR, FT-Raman and UV spectroscopic investigation, electronic properties,
      electric moments, and NBO analysis of anethole using quantum chemical
      calculations.
AB  - FT-IR and FT-Raman spectra of anethole (1-Methoxy-4-(1-propenyl)benzene), a
      flavoring agent of commercial value, have been recorded in the regions 4000-400
      and 4000-100cm(-1) respectively. The structure of the title molecule has been
      optimized and the structural parameters have been calculated by DFT/B3LYP method
      with 6-311++G(d,p) basis set. The fundamental vibrational wavenumbers as well as
      their intensities were calculated and a good agreement between observed and
      scaled calculated wavenumbers has been achieved. UV-Vis spectrum of the title
      compound was recorded in the region 200-500nm and the electronic properties such
      as HOMO and LUMO energies and associated energy gap were calculated by Time
      dependent-density functional theory (TD-DFT) approach. Nonlinear optical (NLO)
      study divulges the nonlinear properties of the molecule. Stability of the title
      molecule arising from hyper-conjugative interactions and charge delocalization
      has been investigated using natural bond orbital (NBO) analysis. The theoretical
      results were found to be in coherence with the measured experimental data. 

PMID- 24934976
TI  - Metabolic profiling of isomeric aglycones central-icaritin (c-IT) and icaritin
      (IT) in osteoporotic rats by UPLC-QTOF-MS.
AB  - The isomers, although of similarly chemical structures, have different
      pharmacological activities due to their metabolic processes in vivo. Central
      icaritin (c-IT) and icaritin (IT) are isomers and major bioactive aglycones of
      the Herba Epimedii. In this study, we found that the anti-osteoporotic effect of
      c-IT was stronger than IT on bone structural changes in osteoporotic rats
      evaluated by Micro-MUCT with the parameters of bone mineral density (BMD), bone
      mineral content (BMC), tissue mineral content (TMC), and tissue mineral density
      (TMD). c-IT treatment significantly increased the bone microarchitecture,
      compared with IT (p < 0.05). In order to explain their differences in anti
      osteoporosis, the metabolic profiling and pathways of c-IT and IT in the plasma,
      bile, urine, and faeces of ovariectomized (OVX) rats were investigated by ultra
      performance liquid chromatography quadrupole time of flight mass spectrometry
      (UPLC-QTOF-MS) after oral administration of c-IT or IT (80 mg/kg). Finally, 59
      metabolites of c-IT and 43 metabolites of IT were identified by elucidating their
      corresponding quasimolecular ions and fragment ions. IT could be quickly absorbed
      into blood and reached a maximum plasma concentration, and then be rapidly
      conversed to its glucuronidation metabolites, most of which were excreted out by
      urine. Interestingly, the absorbed and conjugated speeds of c-IT were slower than
      IT. The metabolic processes of c-IT existed enterohepatic circulation, which
      decreased the metabolism and excretion rate of c-IT, and prolonged the anti
      osteoporosis effect. Our findings provided evidence on the difference on
      metabolic profiles of c-IT and IT in osteoporotic rats, which might shed new
      lights on improving anti-osteoporotic effects of IT and c-IT.

PMID- 24934977
TI  - Preoperative beta-blocker use in coronary artery bypass grafting surgery:
      national database analysis.
AB  - IMPORTANCE: Use of preoperative beta-blockers has been associated with a
      reduction in perioperative mortality for patients undergoing coronary artery
      bypass grafting (CABG) surgery in observational research studies, which led to
      the adoption of preoperative beta-blocker therapy as a national quality standard.
      OBJECTIVE: To determine whether preoperative beta-blocker use within 24 hours of
      CABG surgery is associated with reduced perioperative mortality in a contemporary
      sample of patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of
      the Society of Thoracic Surgeons National Adult Cardiac database for 1107
      hospitals performing cardiac surgery in the United States from January 1, 2008,
      through December 31, 2012. Participants included 506,110 patients 18 years and
      older undergoing nonemergent CABG surgery who had not experienced a myocardial
      infarction in the prior 21 days or any other high-risk presenting symptom. We
      used logistic regression and propensity matching with a greedy 5-to-1 digit
      matching algorithm to examine the association between beta-blocker use and the
      main outcomes of interest. EXPOSURES: Preoperative beta-blocker use. MAIN
      OUTCOMES AND MEASURES: Incidence of perioperative mortality, permanent stroke,
      prolonged ventilation, any reoperation, renal failure, deep sternal wound
      infection, and atrial fibrillation. RESULTS: Among the 506,110 patients
      undergoing CABG surgery who met the inclusion criteria, 86.24% received
      preoperative beta-blockers within 24 hours of surgery. In propensity-matched
      analyses that included 138,542 patients, we found no significant difference
      between patients who did and did not receive preoperative beta-blockers in rates
      of operative mortality (1.12% vs 1.17%; odds ratio [OR], 0.96 [95% CI, 0.87
      1.06]; P = .38), permanent stroke (0.97% vs 0.98%; OR, 0.99 [95% CI, 0.89-1.10];
      P = .81), prolonged ventilation (7.01% vs 6.86%; OR, 1.02 [95% CI, 0.98-1.07]; P
      = .26), any reoperation (3.60% vs 3.69%; OR, 0.97 [95% CI, 0.92-1.03]; P = .35),
      renal failure (2.33% vs 2.24%; OR, 1.04 [95% CI, 0.97-1.11]; P = .30), and deep
      sternal wound infection (0.29% vs 0.34%; OR, 0.86 [95% CI, 0.71-1.04]; P = .12).
      However, patients who received preoperative beta-blockers within 24 hours of
      surgery had higher rates of new-onset atrial fibrillation when compared with
      patients who did not (21.50% vs 20.10%; OR, 1.09 [95% CI, 1.06-1.12]; P < .001).
      Results of logistic regression analyses were broadly consistent. CONCLUSIONS AND
      RELEVANCE: Preoperative beta-blocker use among patients undergoing nonemergent
      CABG surgery who have not had a recent myocardial infarction was not associated
      with improved perioperative outcomes.

PMID- 24934978
TI  - Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat
      diet-induced gain weight and adiposity in female mice.
AB  - AIM: Interleukin-6 (IL-6) is a major cytokine controlling body weight and
      metabolism, but because many types of cells can synthesize and respond to IL-6
      considerable uncertainty still exists about the mechanisms underlying IL-6
      effects. Therefore, the aim of this study was to analyse the effects of tissue
      specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre
      inducible system (aP2-Cre-ERT2). METHODS: Tissue-specific IL-6 KO mice (aP2-IL-6
      KO mice) were produced upon tamoxifen administration and were fed a high-fat diet
      (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. RESULTS: aP2-IL
      6 KO female mice on a HFD gained less weight and adiposity than littermate wild
      type mice, but these effects were not observed in males. Hypothalamic factors
      such as NPY and AgRP showed a pattern of expression consistent with this sex
      specific phenotype. PGC-1alpha expression was increased in several tissues in aP2
      IL-6 KO female mice, which is compatible with increased energy expenditure. Serum
      leptin, insulin, glucose, cholesterol and triglycerides levels were increased by
      HFD, and in females IL-6 deficiency reversed this effect in the case of insulin
      and cholesterol. HFD induced impaired responses to insulin and glucose tolerance
      tests, but no significant differences between genotypes were observed.
      CONCLUSION: The present results demonstrate that deletion of IL-6 driven by aP2
      Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

PMID- 24934980
TI  - Should the patent system for pharmaceuticals be replaced? A theoretical approach.
AB  - This paper acknowledges the difficulties of providing access to innovative drugs
      in some jurisdictions under the patent system and it contributes to the current
      debate on mechanisms aimed at facilitating such access. We employ a highly
      stylized static model of two markets (North and South) to analyse the conditions
      under which a new system based on royalty payments would be preferred to a patent
      system for pharmaceuticals. In the welfare calculations we have considered
      explicitly the influence of marketing activities by the patent owner as well as
      the shadow price of public funds needed to finance the royalties. The bargaining
      power of the firm in terms of obtaining higher compensation is also considered.
      The result: are not unambiguously conclusive being heavily dependent on the
      relevant values of the parameters. Nevertheless, it seems that for realistic
      parameter values, the new system could be preferred by all the parties involved. 

PMID- 24934979
TI  - Functional characterization of histamine H4 receptor on human mast cells.
AB  - Among the four different types of histamine receptors (H1-H4), H4R is
      predominantly expressed in immune cells and involved in immunomodulatory
      response. Here, in this study we determined the expression of H4R in human mast
      cells (HMC-1, LAD-2 and primary cord blood derived CD34+ human mast cells) and
      characterized its functional properties. Interestingly, we found that human mast
      cells responded to both histamine (natural ligand) and 4-methylhistamine
      (selective H4R agonist) for sustained intracellular calcium mobilization,
      degranulation and cytokine production. However, only histamine induced the
      release of cAMP, but 4-methylhistamine down regulates cAMP indicating that H4R
      mediates its effect through Galphai/o protein and H1R via Galphaq protein.
      Furthermore, both histamine and 4-methylhistamine induced the production of
      cysteinyl leukotrienes and LTB4. Using human inflammation antibody array
      membrane, we found that H4R induced the expression of various inflammatory
      proteins, involving pro-inflammatory cytokines and chemokines and these are TGF
      beta1, TNF-alpha, TNF-beta, PDGF-BB, TIMP-2, M-CSF, IP-10, IL-16, IL-6, IL-3, IL
      10, MIP-1alpha, IL-1alpha, ICAM-1, Eotaxin-2, RANTES, IL-8, MCP-1, and IL-6sR. We
      also quantified the level of various inflammatory cytokines produced by human
      mast cells through H4R. It was observed that, the production level of Th2
      cytokines IL-4(401.34 pg/ml), IL-5 (64.21 pg/ml) and IL-13 (1044 pg/ml) and
      classical proinflammatory cytokines IL-6 (221.27 pg/ml) and IL-1beta (34.24
      pg/ml) and chemokines MCP-1(106 pg/ml) and IL-8 (818.32 pg/ml). Furthermore,
      activation of H4R caused the phosphorylation of ERK and PI3K in a time dependent
      manner. Taken together these data demonstrate that, the activation of H4R in
      human mast cells produced not only inflammatory mediators that are associated
      with allergic reactions but also other inflammatory conditions.

PMID- 24934982
TI  - The combined effect of physical, psychosocial/organisational and/or environmental
      risk factors on the presence of work-related musculoskeletal symptoms and its
      consequences.
AB  - This study assessed the combined effect of physical and
      psychosocial/organisational and/or environmental factors on the presence of
      musculoskeletal symptoms (MSS) and its consequences (reduced activities and
      absenteeism due to MSS) in a random sample of 3003 workers in New Zealand. By
      telephone interview, participants reported their current workplace exposures and
      MSS (neck/shoulder, arm/elbow, wrist and low back) and its consequences. Data
      were analysed using multivariable logistic regression. Combined exposure to
      physical and psychosocial/organisational and/or environmental factors increased
      the odds of MSS in the neck/shoulder (OR 3.14, 95% CI 1.79-5.52), arms/elbow
      regions (OR 4.14, 95% CI 2.21-7.76) and low back (OR 1.74, 95% CI 1.28-2.37) and
      its consequences, i.e. reduced activities due to neck/shoulder symptoms (OR 5.45,
      95% CI 2.28-13.00), absenteeism due to neck/shoulder symptoms (OR 5.19, 95% CI
      2.24-12.01) and absenteeism due to low back symptoms (OR 4.37, 95% CI 2.92-6.53).
      In contrast, favourable psychosocial/organisational work conditions reduced the
      odds of wrist symptoms due to poor physical work conditions (OR 2.19, 95% CI 1.44
      3.34). We conclude that to reduce MSS and its consequences, employers need to
      adopt a multifaceted approach: concentrate on improving physical conditions as
      well as the psychosocial/organisational and environmental aspects of the working
      environment. 

PMID- 24934981
TI  - Quantitative group testing-based overlapping pool sequencing to identify rare
      variant carriers.
AB  - BACKGROUND: Genome-wide association studies have revealed that rare variants are
      responsible for a large portion of the heritability of some complex human
      diseases. This highlights the increasing importance of detecting and screening
      for rare variants. Although the massively parallel sequencing technologies have
      greatly reduced the cost of DNA sequencing, the identification of rare variant
      carriers by large-scale re-sequencing remains prohibitively expensive because of
      the huge challenge of constructing libraries for thousands of samples. Recently,
      several studies have reported that techniques from group testing theory and
      compressed sensing could help identify rare variant carriers in large-scale
      samples with few pooled sequencing experiments and a dramatically reduced cost.
      RESULTS: Based on quantitative group testing, we propose an efficient overlapping
      pool sequencing strategy that allows the efficient recovery of variant carriers
      in numerous individuals with much lower costs than conventional methods. We used
      random k-set pool designs to mix samples, and optimized the design parameters
      according to an indicative probability. Based on a mathematical model of
      sequencing depth distribution, an optimal threshold was selected to declare a
      pool positive or negative. Then, using the quantitative information contained in
      the sequencing results, we designed a heuristic Bayesian probability decoding
      algorithm to identify variant carriers. Finally, we conducted in silico
      experiments to find variant carriers among 200 simulated Escherichia coli
      strains. With the simulated pools and publicly available Illumina sequencing
      data, our method correctly identified the variant carriers for 91.5-97.9%
      variants with the variant frequency ranging from 0.5 to 1.5%. CONCLUSIONS: Using
      the number of reads, variant carriers could be identified precisely even though
      samples were randomly selected and pooled. Our method performed better than the
      published DNA Sudoku design and compressed sequencing, especially in reducing the
      required data throughput and cost.

PMID- 24934983
TI  - Effects of portable computing devices on posture, muscle activation levels and
      efficiency.
AB  - Very little research exists on ergonomic exposures when using portable computing
      devices. This study quantified muscle activity (forearm and neck), posture
      (wrist, forearm and neck), and performance (gross typing speed and error rates)
      differences across three portable computing devices (laptop, netbook, and slate
      computer) and two work settings (desk and computer) during data entry tasks.
      Twelve participants completed test sessions on a single computer using a test
      rest-test protocol (30min of work at one work setting, 15min of rest, 30min of
      work at the other work setting). The slate computer resulted in significantly
      more non-neutral wrist, elbow and neck postures, particularly when working on the
      sofa. Performance on the slate computer was four times less than that of the
      other computers, though lower muscle activity levels were also found. Potential
      or injury or illness may be elevated when working on smaller, portable computers
      in non-traditional work settings. 

PMID- 24934985
TI  - Undetectable hepatitis C virus RNA during syphilis infection in two HIV/HCV-co
      infected patients.
AB  - BACKGROUND: Treponema pallidum, the causative agent of syphilis, elicits a
      vigorous immune response in the infected host. This study sought to describe the
      impact of syphilis infection on hepatitis C virus (HCV) RNA levels in patients
      with HIV and chronic HCV infection. METHODS: Patients with chronic HIV/HCV and
      syphilis co-infection were identified by their treating physicians from 1 October
      2010 to 31 December 2013. Stored plasma samples obtained before, during, and
      after syphilis infection were analysed for interleukin (IL)-2, IL-4, IL-6, IL-8,
      IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma),
      and IFN-gamma-inducible protein 10 kDa (IP-10). RESULTS: Undetectable HCV RNA at
      the time of early latent syphilis infection was observed in 2 patients with HIV
      and chronic HCV infection. After treatment of the syphilis infection, HCV RNA
      levels increased again in patient 1, whereas patient 2 initiated HCV therapy and
      remained HCV RNA-negative. Available plasma samples obtained before and after the
      episode with undetectable HCV RNA were phylogenetically identical, making the
      possibility of spontaneous clearance and HCV reinfection less likely. The IL-10,
      TNF-alpha, and IP-10 levels increased at the time of syphilis diagnosis in
      patient 1 and decreased again after treatment of the syphilis infection.
      CONCLUSIONS: We propose that T. pallidum-induced cytokine secretion resulted in
      an immune response hindering HCV replication during syphilis infection. We
      suggest that HIV/HCV-co-infected patients with unexpected undetectable HCV RNA
      are tested for syphilis infection and that the serological tests include both non
      treponemal and treponemal tests to avoid false-positive results caused by HCV.

PMID- 24934984
TI  - Detection of serum antibodies to hepatitis E virus in domestic pigs in Italy
      using a recombinant swine HEV capsid protein.
AB  - BACKGROUND: The hepatitis E virus (HEV) has been detected in both humans and
      animals, particularly pigs, worldwide. Several evidences, including human
      infection following consumption of raw contaminated meat, suggest a zoonotic
      transmission of HEV. In Italy, large circulation of genotype 3 HEV has been
      reported in swine, and recent studies have confirmed the involvement of this
      genotype in autochthonous human cases. RESULT: In this study 111 sera collected
      from healthy pigs in two Italian regions were tested for anti-HEV IgG antibodies.
      For specific HEV antibody detection in swine, we developed ELISA and Western
      blotting methods, using a truncated capsid (ORF2) protein lacking the first 111
      amino acids of a swine HEV genotype 3 strain. The ORF2-based ELISA revealed anti
      HEV antibodies in 104 out of 111 pigs compared with 102 detected with a
      commercial ELISA kit. A lower number of sera reacted with the recombinant ORF2
      protein in a Western blotting format (81/111). Using a Latent class analysis
      (LCA), the estimated sensitivities for ELISA-ORF2 and ELISA-kit tests were 0.961
      and 0.936, respectively, whereas specificities were 0.599 and 0.475. The
      estimated sensitivity of Western blotting was 0.775, and the specificity was
      0.944. CONCLUSIONS: The overall results confirm the high prevalence of HEV
      seropositive healthy pigs in Italy. Through comparisons with a commercial ELISA
      test, the swine genotype 3 HEV antigen produced in this study was proven suitable
      to detect anti-HEV antibodies in pig sera by both ELISA and Western Blotting.

PMID- 24934987
TI  - Depressive symptoms are frequent among drug users, but not associated with
      hepatitis C infection.
AB  - AIM: To compare the prevalence and severity of depressive symptoms among drug
      users with and without hepatitis C virus (HCV) infection. METHODS: This was a
      cross-sectional survey study carried out at the 2 major drug treatment centres on
      the island of Funen, Denmark. Participants were drug users presenting to the 2
      treatment centres. Individuals with chronic hepatitis B virus or HIV infection
      were excluded. Participants completed the Major Depression Inventory (MDI)
      questionnaire when presenting at the centres. Patients with MDI scores indicating
      severe depression (total MDI score >= 35) were referred for treatment evaluation.
      Hepatitis C status was classified by the presence of anti-HCV as a marker of HCV
      exposure and HCV-RNA as a marker of ongoing infection. RESULTS: Two hundred and
      sixty-eight patients were included, of whom 235 (88%) had complete serological
      testing; 100 (43%, 95% confidence interval (CI) 36-49%) had chronic hepatitis C.
      The median MDI score was 22 (interquartile range 12-33); 32% (95% CI 26-39%) had
      a score compatible with depression and 14% (95% CI 10-19%) were rated as severe
      depression. Depression was not associated with hepatitis C (HCV-infected 29%, non
      infected 35%; p = 0.25). Forty-one percent (11/27) of the evaluated participants
      started antidepressant treatment. CONCLUSIONS: Our study demonstrated a high
      prevalence of depressive symptoms among drug users, but this was not more
      frequent among HCV-infected patients. The high overall prevalence of depression
      underlines the relevance of screening for depression in patients who are drug
      users.

PMID- 24934986
TI  - Comparison of two durations of triple-drug therapy in patients with uncomplicated
      brucellosis: A randomized controlled trial.
AB  - BACKGROUND: Brucellosis remains the most common zoonotic disease throughout the
      world and especially in Iran. Several clinical trials have tested different
      therapeutic regimens for brucellosis, but few have assessed the optimal duration
      of treatment. METHODS: We performed a randomized controlled trial to compare a
      triple-drug regimen of doxycycline plus rifampicin for 6 weeks and streptomycin
      for the first 7 days with doxycycline plus rifampicin for 8 weeks and
      streptomycin for 7 days in patients with uncomplicated brucellosis in Arak, Iran.
      The primary outcome measure for the treatment groups was the relapse rate
      measured at 1, 3, 6, 12, and 24 months after cessation of therapy. RESULTS:
      Eligible patients were randomized to one of the 2 groups with 72 per arm. We
      found no significant difference in the relapse rate for the 8-week treatment
      group compared to the 6-week group (9.7% vs 13.9%). There were no significant
      differences between the 6-week and 8-week groups regarding the relapse rate,
      period between clinical presentation and beginning of treatment, and time of
      relapse. Symptom resolution was achieved in all cases at a median 9.5 days and no
      cases experienced continuing symptoms after treatment. CONCLUSIONS: Our trial
      found no significant difference between 6-week and 8-week regimens of doxycycline
      and rifampicin plus streptomycin for the first 7 days. Further comparative
      studies with a large sample size should be implemented to achieve a consistent
      therapeutic regimen for uncomplicated brucellosis, to help identify those who may
      benefit from longer treatment, and to minimize adverse effects and unnecessary
      continuation of treatment.

PMID- 24934988
TI  - Corynebacterium minutissimum vascular graft infection: case report and review of
      281 cases of prosthetic device-related Corynebacterium infection.
AB  - Corynebacterium spp. have proven their pathogenic potential in causing
      infections, particularly in the setting of immunosuppression and prosthetic
      devices. We conducted a PubMed literature review of all cases of Corynebacterium
      prosthetic device infections published in the English language through December
      2013. The majority of cases involved peritoneal dialysis and central venous
      catheters, but prosthetic joints and central nervous system shunts/drains were
      also involved. The management of these cases in terms of retention or removal of
      the device was not uniform; however, the overall mortality remained the same
      among both groups. All of these prosthetic device infections pose potential
      problems in management when the device cannot be removed safely for the patient,
      especially with the lack of data on the pathogenicity of Corynebacterium species.
      However with better identification of species and sensitivities, successful
      treatment is possible even with retention of the device.

PMID- 24934989
TI  - Need for improvements in the surveillance and management of chronic viral
      hepatitis in HIV patients followed in a Danish outpatient clinic.
AB  - OBJECTIVES: The aim of this study was to assess hepatitis B virus (HBV) and
      hepatitis C virus (HCV) surveillance and management in HIV patients currently
      followed in an outpatient clinic at a Danish University Hospital. METHODS:
      Patient data, including demographic characteristics, clinical findings, and
      hepatitis serology, were reviewed at baseline. Patients with incomplete or non
      updated serology within the last 2 y were retested in the next 6 months, and the
      results were reviewed again at follow-up. RESULTS: At baseline, 84% and 74% of
      the 574 HIV patients were found to have incomplete and/or non-updated HBV and HCV
      serology, respectively. At follow-up, updated HBV serology was achieved in 535
      (93%) patients; 15 (3%) patients were found to have a chronic active infection
      and 156 (27%) had a resolved infection, whereas 65 (11%) were vaccinated against
      HBV and 299 (52%) were non-immune. No patients were found to have developed
      chronic HBV infection following HIV diagnosis (equal to 3649 patient-y). Updated
      HCV serology revealed that 25 (4%) had a chronic active HCV infection and 15 (3%)
      had a resolved HCV infection. The anti-HCV incidence rate was 0.27/100 patient-y.
      A liver pathology assessment had not been performed within the last 2 y in 80% of
      the HBV and 32% of the HCV co-infected patients. CONCLUSIONS: Hepatitis screening
      and assessment had been inadequately performed. New cases of chronic hepatitis
      seem to occur infrequently. However, a more proactive hepatitis surveillance and
      management strategy integrated into the overall HIV health care program is
      warranted.

PMID- 24934990
TI  - Molecular analysis of the rpsL gene for rapid detection of streptomycin-resistant
      Mycobacterium tuberculosis: a meta-analysis.
AB  - BACKGROUND: Drug-resistant Mycobacterium tuberculosis (MTB) is a major threat to
      tuberculosis (TB) control programs and public health. Most conventional methods
      of drug susceptibility testing (DST) are precise but time-consuming. Molecular
      analysis of the rpsL gene has been used widely in diagnosing streptomycin
      resistant MTB since it is rapid and specific. The aim of the present study was to
      perform a meta-analysis to assess the accuracy of molecular assay of the rpsL
      gene for the rapid detection of streptomycin-resistant MTB. METHODS: We searched
      PubMed, Web of Science, and EBSCO databases for studies that applied a molecular
      assay of the rpsL gene to detect streptomycin-resistant MTB with a conventional
      method as the reference. The sensitivity and specificity were pooled by a random
      effect model using Meta-DiSc software. A summary receiver operating
      characteristic curve (SROC) was applied to summarize the diagnostic accuracy.
      RESULTS: A total of 22 studies involving 2618 specimens with 1372 streptomycin
      resistant and 1246 streptomycin-susceptible specimens met our inclusion criteria.
      The overall sensitivity and specificity estimates were 0.64 (95% confidence
      interval (CI) 0.61-0.66) and 1.00 (95% CI 0.99-1.00), respectively. The area
      under the SROC curve was 0.9069 and the Cochrane (Q*) index was 0.8387.
      CONCLUSIONS: This meta-analysis reveals that molecular assay of the rpsL gene is
      a reliable and useful method for the detection of streptomycin-resistant MTB.

PMID- 24934991
TI  - Circle-to-circle amplification on a digital microfluidic chip for amplified
      single molecule detection.
AB  - We demonstrate a novel digital microfluidic nucleic acid amplification concept
      which is based on padlock probe mediated DNA detection and isothermal circle-to
      circle amplification (C2CA). This assay platform combines two digital approaches.
      First, digital microfluidic manipulation of droplets which serve as micro
      reaction chambers and shuttling magnetic particles between these droplets
      facilitates the integration of complex solid phase multistep assays. We
      demonstrate an optimized novel particle extraction and transfer protocol for
      superparamagnetic particles on a digital microfluidic chip that allows for nearly
      100% extraction efficiencies securing high assay performance. Second, the
      compartmentalization required for digital single molecule detection is solved by
      simple molecular biological means, circumventing the need for complex
      microfabrication procedures necessary for most, if not all, other digital nucleic
      acid detection methods. For that purpose, padlock probes are circularized in a
      strictly target dependent ligation reaction and amplified through two rounds of
      rolling circle amplification, including an intermediate digestion step. The
      reaction results in hundreds of 500 nm sized individually countable DNA
      nanospheres per detected target molecule. We demonstrate that integrated
      miniaturized digital microfluidic C2CA results in equally high numbers of C2CA
      products MUL(-1) as off-chip tube control experiments indicating high assay
      performance without signal loss. As low as 1 aM synthetic Pseudomonas aeruginosa
      DNA was detected with a linear dynamic range over 4 orders of magnitude up to 10
      fM proving excellent suitability for infectious disease diagnostics. 

PMID- 24934992
TI  - Novel pyrazoline derivatives as bi-inhibitor of COX-2 and B-Raf in treating
      cervical carcinoma.
AB  - Twenty four pyrazoline derivatives modified from Celecoxib were designed and
      synthesized as bi-inhibitor of COX-2 and B-Raf. They were evaluated for their COX
      1/COX-2/B-Raf inhibitory and anti-proliferation activities. Compound A3 displayed
      the most potent activity against COX-2 and HeLa cell line (IC50=0.008 MUM;
      GI50=19.86 MUM) and showed superb COX-1/COX-2 selectivity (>500), being more
      potent and selective than positive control Celecoxib or 5-fluorouracil. Compounds
      A5 and B5 were introduced best B-Raf inhibitory activities (IC50=0.15 MUM and
      0.12 MUM, respectively). Compound A4 retained superb bioactivity against COX-2
      and HeLa cell line (IC50=0.015 MUM; GI50=23.82 MUM) and displayed moderate B-Raf
      inhibitory activity (IC50=3.84 MUM). Docking simulation was conducted to give
      binding patterns. QSAR models were built using bioactivity data and optimized
      conformations to provide a future modification of COX-2/B-Raf inhibitors.

PMID- 24934993
TI  - Coumarin hybrids as novel therapeutic agents.
AB  - Naturally occurring coumarins, having wide spectrum of activities such as
      antioxidant, anti-inflammatory, anticancer, MAO-B inhibitory and antimicrobial,
      are frequently used by the researchers to develop novel synthetic and
      semisynthetic coumarin based therapeutic agents. Many of these agents are hybrid
      molecules, which are designed through concept of molecular hybridization and have
      shown multiple pharmacological activities. This multifunctional attribute of
      these hybrid compounds makes them potential drug candidates for the treatment of
      multifactorial diseases such as cancer, Alzheimer's disease, metabolic syndromes,
      AIDS, malaria, and cardiovascular diseases. The present review compiles research
      reports on development of different coumarin hybrids, classify these on the basis
      of their therapeutic uses and propose structure-activity relationships. It is
      intended to help medicinal chemist in designing and synthesizing novel and potent
      hybrid compounds for the treatment of different disorders. 

PMID- 24934994
TI  - Bacterial community survey of Solenopsis invicta Buren (red imported fire ant)
      colonies in the presence and absence of Solenopsis invicta virus (SINV).
AB  - Insect bacterial symbionts contribute to many essential biological functions of
      their hosts and can also influence host fecundity and fitness. The physiological
      contribution symbionts provide can aid in immune response and xenobiotic
      detoxification. Both of these immune factors can directly impact strategies aimed
      at managing insect populations. One biological control strategy that shows
      promise in insects is the use of single-stranded RNA viruses within the group
      Dicistroviridae. The Solenopsis invicta Virus (SINV; Dicistroviridae), a ssRNA
      virus, has been proposed as a potential biological control agent for the urban
      pest S. invicta Buren or red imported fire ant (RIFA). SINV has been shown to be
      prevalent in RIFA populations of Texas and Florida; however, mortality is
      associated with high viral load. In other insect microbe systems, presence of
      particular bacteria induced resistance against Dicistrovirus. If this type of
      relationship is present in the RIFA-SINV system, their bacterial community could
      reduce the effectiveness of SINV as a biological control system. The advantage of
      454 pyro-sequencing is that it enables classification of unculturable bacteria.
      This study examines the bacterial community in brood, workers, and reproductive
      cast members from colonies with and without SINV infection. Manipulation of the
      bacterial community may alter virus infection and replication within the mid-gut.
      Understanding the differences in the microbial community of ant colonies may
      provide insights that will refine current efforts designing control strategies
      for this important urban pest. 

PMID- 24934995
TI  - 2,3-Dihydroxybenzoic acid electrospun into poly(D,L-lactide)
      (PDLLA)/poly(ethylene oxide) (PEO) nanofibers inhibited the growth of Gram
      positive and Gram-negative bacteria.
AB  - Widespread emergence of antibiotic-resistant pathogens in recent years has
      restricted the treatment options for various infectious diseases. Investigation
      of alternative antimicrobial agents and therapies is thus of utmost importance.
      Electrospinning of 50 mg/ml 2,3-dihydroxybenzoic acid (DHBA) into 24 % (w/v)
      poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO) (1:1) produced
      nanofibers with an average diameter of 401 +/- 122 nm. DHBA released from the
      nanofibers (315 +/- 0.04 ug/ml within 2 h) inhibited the growth of Pseudomonas
      aeruginosa Xen 5, Klebsiella pneumoniae Xen 39, Escherichia coli Xen 14,
      Salmonella typhimurium Xen 26, and Staphylococcus aureus strains Xen 30, Xen 31,
      and Xen 36. The reason for the rapid diffusion of DHBA from PEO:PDLLA may be due
      to formation of hydrogen bonds between the hydroxyl groups of DHBA and the C=O
      groups of the PDLLA. DHBA formed a strong interaction with PDLLA and increased
      the thermal stability of the nanofiber mesh. The DHBA-containing nanofibers were
      non-hemolytic, suggesting that they may be incorporated in the development of a
      wound dressing. 

PMID- 24934996
TI  - Secondary brain abscess following simple renal cyst infection: a case report.
AB  - BACKGROUND: Escherichia coli (E. coli) is the most common causative bacteria of
      neonatal meningitis, but hematogenous intracranial E. coli infection is rare in
      adults. Moreover, intracranial abscess formation owing to E. coli, including
      brain abscesses and subdural empyema formation, is extremely rare. We herein
      present a case involving a patient with a brain abscess owing to E. coli
      following a simple renal cyst infection. A review of the literature is also
      presented. CASE PRESENTATION: A 77-year-old Japanese woman with a history of
      polymyalgia rheumatica was admitted to our hospital because of persistent fever,
      right flank pain, and pyuria. Intravenous antibiotics were administered; however,
      her level of consciousness deteriorated 6 days after admission. Contrast-enhanced
      magnetic resonance imaging showed a brain abscess in the left occipital lobe and
      pyogenic ventriculitis. Enhanced abdominal computed tomography revealed a right
      renal cyst with heterogeneous content. Culture of urine, blood, and aspirated pus
      from the infected cyst revealed E. coli with identical antibiotic sensitivity in
      all sites, suggesting that the cyst infection and subsequent bacteremia might
      have caused the brain abscess. The patient recovered after a 6-week course of
      meropenem. CONCLUSION: The prognosis of patients with E. coli-associated
      intracranial abscess is usually poor. Advanced age and immunosuppression may be
      potent risk factors for intracranial abscess formation owing to the hematogenous
      spread of E. coli.

PMID- 24934997
TI  - Tuning bio-inspired skin-core structure of nascent fiber via interplay of polymer
      phase transitions.
AB  - The properties of polymer fibers are determined by their inner structures. We
      performed dynamic Monte Carlo simulations of early-stage solidification in the
      fluid filaments of stretched polymer solutions after extrusion into a coagulation
      bath upon fiber spinning. We observed that the radial temperature gradient
      dominates polymer crystallization to form an oriented crystalline skin (from
      single to multiple layers), while the radial non-solvent influx dominates phase
      separation to form a concentrated but less oriented core. The skin-core structure
      offers fibers a balanced performance between strength and toughness similar to
      plant stems, which can be tuned by the interplay of phase transitions. Our
      molecular-level observations facilitate a systematic understanding of the
      microscopic mechanism of fiber-spinning, which will pave a way towards making
      excellent polymer fibers. 

PMID- 24934998
TI  - The subjectively perceived quality of postgraduate medical training in
      integrative medicine within the public healthcare systems of Germany and
      Switzerland: the example of anthroposophic hospitals.
AB  - BACKGROUND: Integrative medicine (IM) integrates evidence-based Complementary and
      Alternative Medicine (CAM) with conventional medicine (CON). Medical schools
      offer basic CAM electives but in postgraduate medical training (PGMT) little has
      been done for the integration of CAM. An exception to this is anthroposophic
      medicine (AM), a western form of CAM based on CON, offering an individualized
      holistic IM approach. AM hospitals are part of the public healthcare systems in
      Germany and Switzerland and train AM in PGMT. We performed the first quality
      evaluation of the subjectively perceived quality of this PGMT. METHODS: An
      anonymous full survey of all 214 trainers (TR) and 240 trainees (TE) in all 15 AM
      hospitals in Germany and Switzerland, using the ETHZ questionnaire for annual
      national PGMT assessments in Switzerland (CH) and Germany (D), complemented by a
      module for AM. Data analysis included Cronbach's alpha to assess internal
      consistency questionnaire scales, 2-tailed Pearson correlation of specific
      quality dimensions of PGMT and department size, 2-tailed Wilcoxon Matched-Pair
      test for dependent variables and 2-tailed Mann-Whitney U-test for independent
      variables to calculate group differences. The level of significance was set at p
      < 0.05. RESULTS: Return rates were: D: TE 89/215 (41.39%), TR 78/184 (42.39%);
      CH: TE 19/25 (76%), TR 22/30 (73.33%). Cronbach's alpha values for TE scales were
      >0.8 or >0.9, and >0.7 to >0.5 for TR scales. Swiss hospitals surpassed German
      ones significantly in Global Satisfaction with AM (TR and TE); Clinical
      Competency training in CON (TE) and AM (TE, TR), Error Management, Culture of
      Decision Making, Evidence-based Medicine, and Clinical Competency in internal
      medicine CON and AM (TE). When the comparison was restricted to departments of
      comparable size, differences remained significant for Clinical Competencies in AM
      (TE, TR), and Culture of Decision Making (TE). CON received better grades than AM
      in Global Satisfaction and Clinical Competency. Quality of PGMT depended on
      department size, working conditions and structural training features. CONCLUSION:
      The lower quality of PGMT in German hospitals can be attributed to larger
      departments, more difficult working conditions, and less favorable structural
      features for PGMT in AM, possibly also in relation to increased financial
      pressure.

PMID- 24934999
TI  - Regulation of nitrogenase by reversible mono-ADP-ribosylation.
AB  - Posttranslational modification of proteins plays a key role in the regulation of
      a plethora of metabolic functions. Protein modification by mono-ADP-ribosylation
      was first described as a mechanism of action of bacterial toxins. Since these
      pioneering studies, the number of pathways regulated by ADP-ribosylation in
      organisms from all domains of life expanded significantly. However, in only a few
      cases the full regulatory ADP-ribosylation circuit is known. Here, we review the
      system where mono-ADP-ribosylation regulates the activity of an enzyme: the
      regulation of nitrogenase in bacteria. When the nitrogenase product, ammonium,
      becomes available, the ADP-ribosyltransferase (DraT) covalently links an ADP
      ribose moiety to a specific arginine residue on nitrogenase switching-off
      nitrogenase activity. After ammonium exhaustion, the ADP-ribosylhydrolase (DraG)
      removes the modifying group, restoring nitrogenase activity. DraT and DraG
      activities are reversibly regulated through interaction with PII signaling
      proteins . Bioinformatics analysis showed that DraT homologs are restricted to a
      few nitrogen-fixing bacteria while DraG homologs are widespread in Nature.
      Structural comparisons indicated that bacterial DraG is closely related to
      Archaea and mammalian ADP-ribosylhydrolases (ARH). In all available structures,
      the ARH active site consists of a hydrophilic cleft carrying a binuclear Mg(2+)
      or Mn(2+) cluster, which is critical for catalysis. 

PMID- 24935001
TI  - Lactoferrin for prevention of neonatal sepsis.
AB  - Preterm neonates are at risk to acquire infections. In addition to the high
      mortality associated with sepsis, these patients are at risk for long-term
      disabilities, particularly neurodevelopment impairment. Several interventions
      have been evaluated to reduce rates of infections in neonates but have not proven
      efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory,
      immunomodulatory and anti-microbial properties, has the potential to prevent
      infections in young children. We performed a review of current and ongoing
      clinical trials of LF for prevention of neonatal sepsis, and found eleven
      registered clinical trials that include more than 6,000 subjects. Few of these
      trials have finished; despite their small sample size, the preliminary results
      show a trend towards a positive protective effect of LF on neonatal infections.
      Larger trials are underway to confirm the findings of these initial studies. This
      information will help to define LF's role in clinical settings and, if proven
      effective, would profoundly affect the treatment of low birth weight neonates as
      a cost-effective intervention worldwide. 

PMID- 24935000
TI  - HDAC-inhibition counteracts everolimus resistance in renal cell carcinoma in
      vitro by diminishing cdk2 and cyclin A.
AB  - BACKGROUND: Targeted therapies have improved therapeutic options of treating
      renal cell carcinoma (RCC). However, drug response is temporary due to resistance
      development. METHODS: Functional and molecular changes in RCC Caki-1 cells, after
      acquired resistance to the mammalian target of rapamycin (mTOR)-inhibitor
      everolimus (Cakires), were investigated with and without additional application
      of the histone deacetylase (HDAC)-inhibitor valproic acid (VPA). Cell growth was
      evaluated by MTT assay, cell cycle progression and apoptosis by flow cytometry.
      Target molecules of everolimus and VPA, apoptotic and cell cycle regulating
      proteins were investigated by western blotting. siRNA blockade was performed to
      evaluate the functional relevance of the proteins. RESULTS: Everolimus resistance
      was accompanied by significant increases in the percentage of G2/M-phase cells
      and in the IC50. Akt and p70S6K, targets of everolimus, were activated in Cakires
      compared to drug sensitive cells. The most prominent change in Cakires cells was
      an increase in the cell cycle activating proteins cdk2 and cyclin A. Knock-down
      of cdk2 and cyclin A caused significant growth inhibition in the Cakires cells.
      The HDAC-inhibitor, VPA, counteracted everolimus resistance in Cakires, evidenced
      by a significant decrease in tumor growth and cdk2/cyclin A. CONCLUSION: It is
      concluded that non-response to everolimus is characterized by increased
      cdk2/cyclin A, driving RCC cells into the G2/M-phase. VPA hinders everolimus non
      response by diminishing cdk2/cyclin A. Therefore, treatment with HDAC-inhibitors
      might be an option for patients with advanced renal cell carcinoma and acquired
      everolimus resistance.

PMID- 24935002
TI  - Pretreating lignocellulosic biomass by the concentrated phosphoric acid plus
      hydrogen peroxide (PHP) for enzymatic hydrolysis: evaluating the pretreatment
      flexibility on feedstocks and particle sizes.
AB  - In order to seek a high-efficient pretreatment path for converting
      lignocellulosic feedstocks to fermentable sugars by enzymatic hydrolysis, the
      concentrated H3PO4 plus H2O2 (PHP) was attempted to pretreat different
      lignocellulosic biomass for evaluating the pretreatment flexibility on
      feedstocks. Meanwhile, the responses of pretreatment to particle sizes were also
      evaluated. When the PHP-pretreatment was employed (final H2O2 and H3PO4
      concentration of 1.77% and 80.0%), 71-96% lignin and more than 95% hemicellulose
      in various feedstocks (agricultural residues, hardwood, softwood, bamboo, and
      their mixture, and garden wastes mixture) can be removed. Consequently, more than
      90% glucose conversion was uniformly achieved indicating PHP greatly improved the
      pretreatment flexibility to different feedstocks. Moreover, when wheat straw and
      oak chips were PHP-pretreated with different sizes, the average glucose
      conversion reached 94.9% and 100% with lower coefficient of variation (7.9% and
      0.0%), which implied PHP-pretreatment can significantly weaken the negative
      effects of feedstock sizes on subsequent conversion.

PMID- 24935003
TI  - Microalgae harvesting by flotation using natural saponin and chitosan.
AB  - This study aims to investigate the harvesting of microalgae by dispersed air
      flotation (DiAF) using natural biosurfactant saponin as the collector and
      chitosan as the flocculant. Two types of microalgae, Chlorella vulgaris and
      Scenedesmus obliquus, were used in this study. It was observed that saponin was a
      good frother, but not an effective collector when used alone for flotation
      separation of algae. However, with the pre-flocculation of 5 mg/L of chitosan,
      separation efficiency of >93% microalgae cells was found at 20 mg/L of saponin.
      Removal efficiency of >54.4% and >73.0% was found for polysaccharide and protein,
      respectively at 20 mg/L of saponin and chitosan each. Experimental results show
      that DiAF using saponin and chitosan is effective for separation of microalgae,
      and algogenic organic matter (AOM). It can potentially be applied in the
      integrated microalgae-based biorefinery.

PMID- 24935004
TI  - Co-pelletization of sewage sludge and biomass: the density and hardness of
      pellet.
AB  - In the present study, the effects of process parameters on pellet properties were
      investigated for the co-pelletization of sludge and biomass materials. The
      relaxed pellet density and Meyer hardness of pellets were identified. Scanning
      electron microscopy, FT-IR spectra and chemical analysis were conducted to
      investigate the mechanisms of inter-particular adhesion bonding.
      Thermogravimetric analysis was applied to investigate the combustion
      characteristics. Results showed that the pellet density was increased with the
      parameters increasing, such as pressure, sludge ratio and temperature. High
      hardness pellets could be obtained at low pressure, temperature and biomass size.
      The optimal moisture content for co-pelletization was 10-15%. Moreover, the
      addition of sludge can reduce the diversity of pellet hardness caused by the
      heterogeneity of biomass. Increasing ratio of sludge in the pellet would slow
      down the release of volatile. Synergistic effects of protein and lignin can be
      the mechanism in the co-pelletization of sludge and biomass. 

PMID- 24935005
TI  - Investigation on thermochemical behavior of co-pyrolysis between oil-palm solid
      wastes and paper sludge.
AB  - The pyrolysis characteristics of oil-palm solid wastes, paper sludge and their
      blends were studied via thermogravimetric analysis. Blends ranging from 10 wt.%
      to 90 wt.% on dosage ratio were prepared to investigate their co-pyrolysis
      behavior and kinetics. There was a synergistic interaction at low temperature
      during co-pyrolysis between oil-palm solid wastes and paper sludge. The
      synergistic interaction would improve thermochemical pyrolysis reactivity of the
      blends, which could be attributed to the hydrogenation role and the potential
      mineral catalytic effects on paper sludge pyrolysis. The value of average
      activation energy obtained by Starink and Friedmen methods did not gradually
      decline with the increasing proportion of oil-palm solid wastes in the blends.
      The lowest average activation energy was achieved when the percentage of oil-palm
      solid wastes was 70%, which was 152 kJ/mol by Starink and 149 kJ/mol by Friedmen,
      respectively.

PMID- 24935006
TI  - Improvement of power generation using Shewanella putrefaciens mediated bioanode
      in a single chambered microbial fuel cell: effect of different anodic operating
      conditions.
AB  - Three different approaches were employed to improve single chambered microbial
      fuel cell (sMFC) performance using Shewanella putrefaciens as biocatalyst.
      Taguchi design was used to identify the key process parameter (anolyte
      concentration, CaCl2 and initial anolyte pH) for maximization of volumetric
      power. Supplementation of CaCl2 was found most significant and maximum power
      density of 4.92 W/m(3) was achieved. In subsequent approaches, effect on power
      output by riboflavin supplementation to anolyte and anode surface modification
      using nano-hematite (Fe2O3) was observed. Volumetric power density was increased
      by 44% with addition of 100 nM riboflavin to anolyte while with 0.8 mg/cm(2) nano
      Fe2O3 impregnated anode power density and columbic efficiency increased by 40%
      and 33% respectively. Cyclic voltammetry revealed improvement in electrochemical
      activity of Shewanella with nano-Fe2O3 loading and electrochemical impedance
      depicted inverse relationship between charge transfer resistance and nano-Fe2O3
      loading. This study suggests anodic improvement strategies for maximization of
      power output.

PMID- 24935007
TI  - Trehalose enhancing microbial electrolysis cell for hydrogen generation in low
      temperature (0  degrees C).
AB  - This work explored the feasibility of a method combining physical (sonication and
      base) and biological (partial fermentation) processes for sludge treatment and
      the effects of trehalose on the hydrogen generation of microbial electrolysis
      cell at 0  degrees C. The results demonstrated that the above pretreatment method
      was favorable, which promoted organics decomposing into lower molecular weight
      matter. The promotion of trehalose for MEC efficiency was obvious and the optimal
      concentration of trehalose was 50 mmol/L. With this concentration, the highest
      hydrogen recovery rate was 0.25 m(3)-H2/-m(3)-reactor per day. Coulomb efficiency
      and energy recovery efficiency were 46.4% and 203%, respectively. Further, the
      consumption order of mixed substances was VFAs>proteins>carbohydrates. For
      microorganism community, SEM photographs illustrated that the selectivity of
      environmental temperature for the species of anode bacteria was strong and
      denaturing gradient gel electrophoresis indicated that Microbacterium and
      Proteobacteria were the two main species and Proteobacteria may be one of the
      species that produced electrons.

PMID- 24935008
TI  - Activation of oncogenic pathways in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic,
      progressive fibrosing interstitial pneumonia of unknown cause. The most recent
      hypotheses on IPF pathogenesis suggest a central role of epithelial cell damage,
      followed by a dysregulated molecular cross talk between epithelial cells and
      fibroblasts. Thus, IPF progression has often been assimilated to that of cancer,
      and several signaling patterns appear to be disrupted in both diseases. Here, we
      analyze the expression in an IPF series of a panel of molecules, which are known
      to play a role in tumorigenic process. Our findings, although preliminary, reveal
      that IPF landscape is enriched in neoplastic potential expressed in a context of
      complex genomic polyclonality and cellular heterogeneity. These results provide a
      rationale for further investigations aimed to exploit-in a similar fashion to
      cancer-targeted therapies for a "precision medicine" approach to IPF. 

PMID- 24935009
TI  - Constipation misperception is associated with gender, marital status, treatment
      utilization and constipation symptoms experienced.
AB  - BACKGROUND/AIMS: It is essential that clinicians have an understanding of
      patients' perceptions of constipation as well as constipation mis-perception
      (CM), which can be defined as failure to recognize the six constipation symptoms
      (infrequency, straining, hard stool, incomplete evacuation, anorectal obstruction
      or manual maneuver). The aims of our study were to identify the prevalence of CM
      and its association with demographics and clinical features. METHODS: This
      nationwide survey included 625 self-reported constipated subjects (431 females;
      mean age, 41.2 years) among random participants in the National Health Screening
      Program. The prevalence of CM for each constipation symptom was estimated, and
      the participants were classified into nil (0), low (1-2), mid (3-4) and high (5
      6) level CM subgroups according to the number of misperceived symptoms. RESULTS:
      The highest rate of CM was observed for manual maneuver (48.3%), followed by
      anorectal obstruction (38.4%), stool infrequency (34.6%), incomplete evacuation
      (32.2%), hard stool (27.2%) and straining (25.4%). Among the nil (n = 153), low
      (n = 242), mid (n = 144) and high level (n = 86) subgroups, there were
      significant differences in the proportions of males (18.3%, 34.3%, 39.6% and
      30.2%; P = 0.001, respectively), never-married status (25.7%, 38.2%, 36.8% and
      45.9%; P = 0.030, respectively) and those who did not receive treatment for
      constipation (41.8%, 47.5%, 58.3% and 66.3%; P < 0.001, respectively). There was
      a significant linear trend of increasing degree of CM with decreasing symptoms
      experienced (P < 0.001). CONCLUSIONS: CM is significantly associated with gender,
      marital status, treatment utilization and the range of constipation symptoms
      experienced.

PMID- 24935010
TI  - European perspective for effective cancer drug development.
AB  - Health systems and the clinical research landscape evolve continuously owing to
      increased risk aversion, scrutiny by funding bodies, and costs of clinical
      trials. In this context, however, current drug development procedures are far
      from optimal, as exemplified by the late-stage failure of several drugs. The
      identification of new drugs urgently requires approaches based on a solid
      understanding of cancer biology, and that will support the design of robust
      confirmatory trials. The complexity and the costs of drug development are now
      beyond the knowledge and operational capacity of single organisations, therefore,
      a drastic deviation from the traditional path of drug discovery and new forms of
      multidisciplinary partnerships are needed to succeed in this sector. The European
      Organisation for Research and Treatment of Cancer (EORTC) proposes the use of
      collaborative molecular screening platforms (CMSPs) as a new approach to tackle
      this issue. These CMSPs have the advantage of optimizing the expertise of several
      partners and combining efforts alongside with cost-sharing models for efficient
      patient selection. This article describes some of the challenges to advancing
      drug development and improving medical treatments and how these hurdles can be
      overcome.

PMID- 24935013
TI  - Targeted therapies: ibrutinib resonates with us.

PMID- 24935014
TI  - Haematological cancer: the translocation behind follicular lymphoma development.

PMID- 24935018
TI  - A definition of recovery in myalgic encephalomyelitis and chronic fatigue
      syndrome should be based upon objective measures.
AB  - INTRODUCTION: Adamowicz and colleagues recently proposed to use "a consistent
      definition of recovery that captures a broad-based return to health with
      assessments of both fatigue and function as well as the patients' perceptions of
      his/her recovery status" for patients with chronic fatigue syndrome (CFS).
      METHODS: A qualitative analysis of case definitions for Myalgic encephalomyelitis
      (ME) and CFS and methods to assess the symptoms and clinical status of ME and CFS
      patients objectively. RESULTS: The criteria of CFS define a heterogeneous
      disorder. ME, often used interchangeably with CFS, is principally defined by
      muscle weakness, cognitive impairment etc., but above all post-exertional
      "malaise": a long-lasting increase in symptoms, e.g. muscle pain and cognitive
      deficits, after a minor exertion. The principle symptom of CFS however is
      "chronic fatigue". Since post-exertional "malaise" is not obligatory for CFS,
      only part of the CFS patients meet the diagnostic criteria for ME, while not all
      ME patients qualify as CFS patients. There are several accepted methods to assess
      characteristic symptoms and the clinical status of ME and CFS patients using
      objective measures, e.g. (repeated) cardiopulmonary exercise tests. CONCLUSION:
      To resolve the debate about the clinical status, proposed effectiveness of
      therapies and recovery in ME and CFS, it is crucial to accurately diagnose
      patients using well-defined criteria for ME and CFS and an objective assessment
      of various typical symptoms, since subjective measures such as "fatigue" will
      perpetuate the debate.

PMID- 24935016
TI  - Sinonasal carcinoma: clinical, pathological, genetic and therapeutic advances.
AB  - The sinonasal cavities represent an anatomical region affected by a variety of
      tumours with clinical, aetiological, pathological, and genetic features distinct
      from tumours at the main head and neck cancer localizations. Together, squamous
      cell carcinoma and adenocarcinoma account for 80% of all sinonasal tumours, and
      are aetiologically associated with professional exposure to wood and leather dust
      particles and other industrial compounds, and therefore, are officially
      recognized as an occupational disease. Owing to their distinctive
      characteristics, sinonasal tumours should be considered as separate entities, not
      to be included in the miscellany of head and neck cancers. Sinonasal tumours are
      rare, with an annual incidence of approximately 1 case per 100,000 inhabitants
      worldwide, a fact that has hampered molecular-genetic studies of the tumorigenic
      pathways and the testing of alternative treatment strategies. Nevertheless, the
      clinical management of sinonasal cancer has improved owing to advances in imaging
      techniques, endoscopic surgical approaches, and radiotherapy. Genetic profiling
      and the development of in vitro cell lines and animal models currently form the
      basis for future targeted anticancer therapies. We review these advances in our
      understanding and treatment of sinonasal tumours. 

PMID- 24935019
TI  - Authors' response to commentary by Twisk.

PMID- 24935017
TI  - Psychological states, serum markers and survival: associations and predictors of
      survival in patients with renal cell carcinoma.
AB  - This study sought to determine if there was an association between prognostic
      based serum biomarkers, survival, and psychosocial factors in patients with
      metastatic renal cell carcinoma. Associations were found between psychosocial
      factors and biomarker levels (hemoglobin with depressive symptoms (r = -0.29),
      positive affect (r = 0.30), social support (r = 0.19), and perceived stress (r = 
      0.27); albumin with depressive symptoms (r = -0.19), positive affect (r = 0.22),
      and social support (r = 0.20); alkaline phosphatase with depressive symptoms (r =
      0.21), all p values <0.05. After adjustment for disease-related risk factors,
      only the associations between positive affect and perceived stress with
      hemoglobin remained significant (p's < 0.05). Positive affect (HR = 0.90; 95% CI
      = 0.83, 0.97; p = 0.009) and depressive symptom total scores (HR = 1.03; 95% CI =
      1.01, 1.06; p = 0.013), and alkaline phosphatase (HR 2.72; 95% CI = 1.41, 5.24; p
      = 0.003) were associated with survival. This study suggests that measures of
      positive and negative psychological outlook may contribute differently to health,
      well-being, and survival.

PMID- 24935020
TI  - Heart rate following short-term beta-blocker titration predicts all-cause
      mortality in elderly chronic heart failure patients: insights from the CIBIS-ELD
      trial.
AB  - AIMS: Beta-blockers (BBs) improve outcomes in heart failure. Results from the
      Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously
      demonstrated the feasibility of heart rate, not maximum dose, as a treatment
      goal. In this pre-specified analysis, we investigated the prognostic value of
      achieved heart rate after BB optimization on long-term mortality. METHODS AND
      RESULTS: Elderly heart failure patients from the CIBIS-ELD trial were invited to
      participate in a follow-up examination 4 years after the initial 12-week BB up
      titration period. The relationship between all-cause mortality, BB dose, and
      heart rate after titration and potentially confounding clinical variables was
      analysed by multivariable Cox regression. In total, 728 patients (38% women; mean
      age 72.9 +/- 5.4 years) were included. During a mean follow-up period of 45 +/- 9
      months, 134 patients (19%) died, thus accumulating 2268 patient-years at risk.
      There was no significant difference in baseline heart rate for survivors and non
      survivors (P = 0.19). In models adjusting for age, sex, BB pre-treatment,
      ventricular function, heart rate, and NYHA class at baseline, a heart rate
      increase by 10 b.p.m. following up-titration was associated with a subsequent
      mortality hazard ratio of 1.19 (95% confidence interval 1.02-1.38, P = 0.023).
      The heart rate range with the lowest mortality and the fewest treatment-related
      adverse events was 55-64 b.p.m. The achieved BB dose was not associated with
      mortality risk. CONCLUSION: The heart rate after up-titration, but not BB dose,
      predicted all-cause mortality risk in elderly patients with chronic heart
      failure. These patients should be titrated to resting heart rates between 55 and
      64 b.p.m.

PMID- 24935021
TI  - Assessing Online Collaborative Discourse.
AB  - PURPOSE: This qualitative study using transcript analysis was undertaken to
      clarify the value of Harasim's Online Collaborative Learning Theory as a way to
      assess the collaborative process within nursing education. The theory
      incorporated three phases: (a) idea generating; (b) idea organizing; and (c)
      intellectual convergence. METHOD: The transcripts of asynchronous discussions
      from a 2-week module about disaster nursing using a virtual community were
      analyzed and formed the data for this study. FINDINGS: This study supports the
      use of Online Collaborative Learning Theory as a framework for assessing online
      collaborative discourse. Individual or group outcomes were required for the
      students to move through all three phases of the theory. DISCUSSION/CONCLUSION:
      The phases of the Online Collaborative Learning Theory could be used to evaluate
      the student's ability to collaborate. It is recommended that group process
      skills, which have more to do with interpersonal skills, be evaluated separately
      from collaborative learning, which has more to do with cognitive skills. Both are
      required for practicing nurses. When evaluated separately, the student learning
      needs are more clearly delineated.

PMID- 24935022
TI  - Nanostructured electrochromic smart windows: traditional materials and NIR
      selective plasmonic nanocrystals.
AB  - Electrochromic devices, which dynamically change colour under applied potential,
      are widely studied for use in energy-efficient smart windows. To improve the
      viability of smart windows, many researchers are utilizing nanomaterials, which
      can provide electrochromic devices with improved colouration efficiencies, faster
      switching times, longer cycle lives, and potentially reduced costs. In an effort
      to demonstrate a new type of electrochromic device that goes beyond the
      capabilities of commonly used electrochromic materials, researchers have turned
      to plasmonic transparent conductive oxide (TCO) nanocrystals. Electrochemical
      injection of electrons into plasmonic TCO nanocrystal films induces a shift in
      the plasmon frequency and gives rise to the new functionality of selective
      optical modulation in the near-infrared region of the solar spectrum. These
      nanocrystals can be used as building blocks to enable creation of advanced
      electrochromic devices containing mesoporous electrodes or nanocrystal-in-glass
      composites. Such devices have been important in advancing the field towards
      achieving the ideal smart window with independent control over visible and NIR
      transmittance. 

PMID- 24935023
TI  - Biomass production and nutrient removal by Chlorella sp. as affected by sludge
      liquor concentration.
AB  - The use of microalgae for biomass production and nutrient removal from the reject
      water produced in the dewatering process of anaerobically digested sludge, sludge
      liquor, was investigated. The sludge liquor was characterized by a high content
      of total suspended solids (1590 mg L(-1)), a high nitrogen concentration (1210 mg
      L(-1)), and a low phosphorus concentration (28 mg L(-1)). Chlorella sp. was grown
      in sludge liquor diluted with wastewater treatment plant effluent water to
      different concentrations (12, 25, 40, 50, 70, and 100%) using batch mode. The
      environmental conditions were 25  degrees C, a continuous lightning of 115 MUmol
      m(-2) s(-1), and a CO2 concentration of 3.0%. The highest biomass production
      (0.42-0.45 g dry weight L(-1) Day(-1)) was achieved at 40-50% sludge liquor,
      which was comparable to the production of the control culture grown with an
      artificial fertilizer. The biomass production was 0.12 and 0.26 g dry weight L(
      1) Day(-1) at 12% and 100% sludge liquor, respectively. The percentage of
      nitrogen in the algal biomass increased from 3.6% in 12% sludge liquor and
      reached a saturation of ~10% in concentrations with 50% sludge liquor and higher.
      The phosphorus content in the biomass increased linearly from 0.2 to 1.5% with
      increasing sludge liquor concentrations. The highest nitrogen removal rates by
      algal biosynthesis were 33.6-42.6 mg TN L(-1) Day(-1) at 40-70% sludge liquor,
      while the highest phosphorus removal rates were 3.1-4.1 mg TP L(-1) Day(-1) at 50
      100% sludge liquor. 

PMID- 24935025
TI  - Counterflow isotachophoresis in a monolithic column.
AB  - This study describes stationary counterflow isotachophoresis (ITP) in a
      poly(acrylamide-co-N,N'-methylenebisacrylamide) monolithic column as a means for
      improving ITP processing capacity and reducing dispersion. The flow profile in
      the monolith was predicted using COMSOL's Brinkman Equation application mode,
      which revealed that the flow profile was mainly determined by monolith
      permeability. As monolith permeability decreases, the flow profile changes from a
      parabolic shape to a plug shape. An experimental monolithic column was prepared
      in a fused-silica capillary using an ultraviolet-initiated polymerization method.
      A monolithic column made from 8% (wt.) monomer was chosen for the stationary
      counterflow ITP experiments. Counterflow ITP in the monolithic column showed
      undistorted analyte zones with significantly reduced dispersion compared to the
      severe dispersion observed in an open capillary. Particularly, for r
      phycoerythrin focused by counterflow ITP, its zone width in the monolithic column
      was only one-third that observed in an open capillary. These experiments
      demonstrate that stationary counterflow ITP in monoliths can be a robust and
      practical electrofocusing method. 

PMID- 24935026
TI  - Ultrasound assisted transesterification of waste cooking oil using heterogeneous
      solid catalyst.
AB  - Transesterification based biodiesel production from waste cooking oil in the
      presence of heterogeneous solid catalyst has been investigated in the present
      work. The effect of different operating parameters such as type of catalyst,
      catalyst concentration, oil to methanol molar ratio and the reaction temperature
      on the progress of the reaction was studied. Some studies related to catalyst
      reusability have also been performed. The important physicochemical properties of
      the synthesized biodiesel have also been investigated. The results showed that
      tri-potassium phosphate exhibits high catalytic activity for the
      transesterification of waste cooking oil. Under the optimal conditions, viz.
      catalyst concentration of 3wt% K3PO4, oil to methanol molar ratio of 1:6 and
      temperature of 50 degrees C, 92.0% of biodiesel yield was obtained in 90min of
      reaction time. Higher yield was obtained in the presence of ultrasound as
      compared to conventional approach under otherwise similar conditions, which can
      be attributed to the cavitational effects. Kinetic studies have been carried out
      to determine the rate constant at different operating temperatures. It was
      observed that the kinetic rate constant increased with an increase in the
      temperature and the activation energy was found to be 64.241kJ/mol. 

PMID- 24935024
TI  - Curative vs. preventive management of nitrogen transfers in rural areas: lessons
      from the case of the Orgeval watershed (Seine River basin, France).
AB  - The Orgeval watershed (104 km(2)) is a long-term experimental observatory and
      research site, representative of rural areas with intensive cereal farming of the
      temperate world. Since the past few years, we have been carrying out several
      studies on nitrate source, transformation and transfer of both surface and
      groundwaters in relation with land use and agriculture practices in order to
      assess nitrate (NO3(-)) leaching, contamination of aquifers, denitrification
      processes and associated nitrous oxide (N2O) emissions. A synthesis of these
      studies is presented to establish a quantitative diagnosis of nitrate
      contamination and N2O emissions at the watershed scale. Taking this watershed as
      a practical example, we compare curative management measures, such as pond
      introduction, and preventive measures, namely conversion to organic farming
      practices, using model simulations. It is concluded that only preventive measures
      are able to reduce the NO3(-) contamination level without further increasing N2O
      emissions, a result providing new insights for future management bringing
      together water-agro-ecosystems. 

PMID- 24935027
TI  - Oil-water de-emulsification using ultrasonic technology.
AB  - In this paper an oil-water de-emulsification process within large tanks using
      ultrasonic technology is presented. As the device would operate in hazardous
      areas, it should not consume an excessive amount of electrical power. Hence, the
      paper investigates the suitable oil-water concentrations (10-90% concentrations
      in step of 10%) which would lead to the fastest separation while consuming the
      minimum amount of power. Extensive experiments which were conducted using a
      powerful 20kHz ultrasonic sensor were indicative with good repeatability that the
      emulsion layer with less water content (i.e. 10 to 40% water-cut) gets
      significantly faster separation. The experimental study was then validated
      through a set of finite element-based simulations for different ratios of oil
      water emulsions. This led to suggest a new feasible de-emulsifying device which
      consists of a one dimensional array of ultrasonic sensors which are vertically
      distributed to emit ultrasonic waves in horizontal direction and in a time
      multiplexed manner. 

PMID- 24935028
TI  - 'The living death of Alzheimer's' versus 'Take a walk to keep dementia at bay':
      representations of dementia in print media and carer discourse.
AB  - Understanding dementia is a pressing social challenge. This article draws on the
      'Dementia talking: care conversation and communication' project which aims to
      understand how talk about, and to people living with dementia is constructed. In
      this article I draw on the construction of dementia manifest in two data sets - a
      corpus of 350 recent UK national newspaper articles and qualitative data derived
      from in-depth interviews with informal carers. These data were analysed using a
      thematic discursive approach. A 'panic-blame' framework was evident in much of
      the print media coverage. Dementia was represented in catastrophic terms as a
      'tsunami' and 'worse than death', juxtaposed with coverage of individualistic
      behavioural change and lifestyle recommendations to 'stave off' the condition.
      Contrary to this media discourse, in carers' talk there was scant use of
      hyperbolic metaphor or reference to individual responsibility for dementia, and
      any corresponding blame and accountability. I argue that the presence of
      individualistic dementia 'preventative' behaviour in media discourse is
      problematic, especially in comparison to other more 'controllable' and treatable
      chronic conditions. Engagement with, and critique of, the nascent panic-blame
      cultural context may be fruitful in enhancing positive social change for people
      diagnosed with dementia and their carers.

PMID- 24935029
TI  - The future of quantum dots in drug discovery.
AB  - The rapid development of drug discovery today is inseparable from the interaction
      of advanced particle technologies and new drug synthesis protocols. Quantum dots
      (QDs) are regarded as a unique class of fluorescent labels, with unique optical
      properties such as high brightness and long-term colloidal and optical stability;
      these are suitable for optical imaging, drug delivery and optical tracking,
      fluorescence immunoassay and other medicinal applications. More importantly, QD
      possesses a rich surface chemistry property that is useful for incorporating
      various drug molecules, targeting ligands, and additional contrast agents (e.g.,
      MRI, PET, etc.) onto the nanoparticle surface for achieving targeted and
      traceable drug delivery therapy at both cellular and systemic levels. In recent
      times, the advancement of QD technology has promoted the use of functionalized
      nanocrystals for in vivo applications. Such research is paving the way for drug
      discovery using various bioconjugated QD formulations. In this editorial, the
      authors highlight the current research progress and future applications of QDs in
      drug discovery. 

PMID- 24935030
TI  - Development of a BALB/c 3T3 neutral red uptake cytotoxicity test using a
      mainstream cigarette smoke exposure system.
AB  - BACKGROUND: Tobacco smoke toxicity has traditionally been assessed using the
      particulate fraction under submerged culture conditions which omits the vapour
      phase elements from any subsequent analysis. Therefore, methodologies that assess
      the full interactions and complexities of tobacco smoke are required. Here we
      describe the adaption of a modified BALB/c 3T3 neutral red uptake (NRU)
      cytotoxicity test methodology, which is based on the Interagency Coordinating
      Committee on the Validation of Alternative Methods (ICCVAM) protocol for in vitro
      acute toxicity testing. The methodology described takes into account the
      synergies of both the particulate and vapour phase of tobacco smoke. This is of
      particular importance as both phases have been independently shown to induce in
      vitro cellular cytotoxicity. FINDINGS: The findings from this study indicate that
      mainstream tobacco smoke and the gas vapour phase (GVP), generated using the
      Vitrocell(r) VC 10 smoke exposure system, have distinct and significantly
      different toxicity profiles. Within the system tested, mainstream tobacco smoke
      produced a dilution IC50 (dilution (L/min) at which 50% cytotoxicity is observed)
      of 6.02 L/min, whereas the GVP produced a dilution IC50 of 3.20 L/min. In
      addition, we also demonstrated significant dose-for-dose differences between
      mainstream cigarette smoke and the GVP fraction (P < 0.05). This demonstrates the
      importance of testing the entire tobacco smoke aerosol and not just the
      particulate fraction, as has been the historical preference. CONCLUSIONS: We have
      adapted the NRU methodology based on the ICCVAM protocol to capture the full
      interactions and complexities of tobacco smoke. This methodology could also be
      used to assess the performance of traditional cigarettes, blend and filter
      technologies, tobacco smoke fractions and individual test aerosols.

PMID- 24935031
TI  - Strong oviposition preference for Bt over non-Bt maize in Spodoptera frugiperda
      and its implications for the evolution of resistance.
AB  - BACKGROUND: Transgenic crops expressing Bt toxins have substantial benefits for
      growers in terms of reduced synthetic insecticide inputs, area-wide pest
      management and yield. This valuable technology depends upon delaying the
      evolution of resistance. The 'high dose/refuge strategy', in which a refuge of
      non-Bt plants is planted in close proximity to the Bt crop, is the foundation of
      most existing resistance management. Most theoretical analyses of the high
      dose/refuge strategy assume random oviposition across refugia and Bt crops.
      RESULTS: In this study we examined oviposition and survival of Spodoptera
      frugiperda across conventional and Bt maize and explored the impact of
      oviposition behavior on the evolution of resistance in simulation models. Over
      six growing seasons oviposition rates per plant were higher in Bt crops than in
      refugia. The Cry1F Bt maize variety retained largely undamaged leaves, and
      oviposition preference was correlated with the level of feeding damage in the
      refuge. In simulation models, damage-avoiding oviposition accelerated the
      evolution of resistance and either led to requirements for larger refugia or
      undermined resistance management altogether. Since larval densities affected
      oviposition preferences, pest population dynamics affected resistance evolution:
      larger refugia were weakly beneficial for resistance management if they increased
      pest population sizes and the concomitant degree of leaf damage. CONCLUSIONS:
      Damaged host plants have reduced attractiveness to many insect pests, and crops
      expressing Bt toxins are generally less damaged than conventional counterparts.
      Resistance management strategies should take account of this behavior, as it has
      the potential to undermine the effectiveness of existing practice, especially in
      the tropics where many pests are polyvoltinous. Efforts to bring down total pest
      population sizes and/or increase the attractiveness of damaged conventional
      plants will have substantial benefits for slowing the evolution of resistance.

PMID- 24935032
TI  - In vitro analysis of the susceptibility of HIV-1 subtype A and CRF01_AE
      integrases to raltegravir.
AB  - The antiviral efficacy of raltegravir (RAL) has been proven against human
      immunodeficiency virus type 1 (HIV-1) subtypes B and C but remained to be
      determined against other subtypes. Therefore, the enzymatic activities as well as
      RAL resistance of HIV-1 subtype A and CRF01_AE integrases (INs) were
      investigated. Previously published subtype A and CRF01_AE IN sequences from RAL
      naive patients were aligned to generate consensus sequences for both IN subtypes.
      Subtype A and CRF01_AE INs encoded by these consensus sequences as well as the
      corresponding enzymes harbouring the N155H resistance mutation were expressed and
      purified. Enzymatic activities of subtype A and CRF01_AE INs were analysed with
      regard to typical 3'-end processing (3'-P) and strand transfer (ST) activities
      both in the presence and absence of RAL and were compared with subtype B IN as
      well as with the corresponding INs harbouring the N155H resistance mutation.
      Subtypes B, A and CRF01_AE INs showed similar 3'-P and ST activities. In the
      presence of RAL, the three wild-type INs exhibited ST activity IC50 values (50%
      inhibitory concentrations) of 86.3 +/- 32.5, 158.3 +/- 99.0 and 100.0 +/- 65.7
      nM, respectively. Analysis of 3'-P activity in the presence of RAL revealed
      IC(50) > 10 MUM for all three enzymes. The three INs harbouring the N155H
      mutation presented in vitro low but similar resistance levels to RAL. In
      conclusion, INs from HIV-1 subtypes B, A and CRF01_AE showed similar responses to
      RAL in vitro, suggesting the potency of this antiretroviral drug to treat HIV-1
      subtype A- and CRF01_AE-infected patients.

PMID- 24935033
TI  - High dynamic range proteome imaging with the structured illumination gel imager.
AB  - A current challenge for proteomics is detecting proteins over the large
      concentration ranges found in complex biological samples such as whole-cell
      extracts. Currently, no unbiased, whole-proteome analysis scheme is capable of
      detecting the full range of cellular proteins. This is due in part to the limited
      dynamic range of the detectors used to sense proteins or peptides. We present a
      new technology, structured illumination (SI) gel imager, which detects
      fluorescently labeled proteins in electrophoretic gels over a 1 000 000-fold
      concentration range. SI uses computer-generated masks to attenuate the
      illumination of highly abundant proteins, allowing for long exposures of low
      abundance proteins, thus avoiding detector saturation. A series of progressively
      masked gel images are assembled into a single, very high dynamic range image. We
      demonstrate that the SI imager can detect proteins over a concentration range of
      approximately 1 000 000-fold, making it a useful tool for comprehensive, unbiased
      proteome-wide surveys.

PMID- 24935034
TI  - Biomask for skin regeneration.

PMID- 24935035
TI  - Tissue-engineered collagen grafts to treat large tendon defects.

PMID- 24935036
TI  - Recent progress on the development of gene-activated scaffolds encoding PDGF for
      enhanced bone regeneration.

PMID- 24935037
TI  - Stem cells show promise in the treatment of failing hearts.

PMID- 24935040
TI  - Safety and feasibility of intramyocardial versus intracoronary delivery of
      autologous cell therapy in advanced heart failure: the REGENERATE-IHD pilot
      study.
AB  - AIM: This study presents an interim safety and feasibility analysis of the
      REGENERATE-IHD randomized controlled trial, which is examining the safety and
      efficacy of three different delivery routes of bone marrow-derived stem cells
      (BMSCs) in patients with ischemic heart failure. METHODS & RESULTS: The first 58
      patients recruited to the REGENERATE-IHD study are included in this interim
      analysis (pilot). Symptomatic patients with ischemic heart failure were
      randomized to receive subcutaneous granulocyte colony-stimulating factor or
      saline injections only; or subcutaneous granulocyte colony-stimulating factor
      injections followed by intracoronary or intramyocardial injections of BMSCs or
      serum (control). No significant differences were found in terms of safety and
      feasibility between the different delivery routes, with no significant difference
      in procedural complications or major adverse cardiac events. There was a signal
      towards improved heart failure symptoms in the patients treated with
      intramyocardial injection of mobilized BMSCs. CONCLUSION: Peripheral mobilization
      of BMSCs with or without subsequent direct myocardial delivery appears safe and
      feasible in patients with chronic ischemic heart failure.

PMID- 24935041
TI  - Negative neuronal differentiation of human adipose-derived stem cell clones.
AB  - AIMS: Adipose mesenchymal stem cells are a heterogeneous population. Therefore,
      the question posed in this study is whether the heterogenic differentiation
      potential exhibited by the different clones toward mesodermic lineages can be
      extended to nonmesodermic lineages, such as the neuroectoderm. MATERIALS &
      METHODS: Different single cell clones of human adipose mesenchymal stem cells
      from the same donor were isolated. Neuronal plasticity of the clones was assessed
      according to the pattern DNA methylation, gene expression and intracellular
      calcium responses. RESULTS: Under neurogenic culture conditions, clones presented
      variable expression of neuronal-specific genes, but still expressed osteogenic
      markers. No calcium response was exhibited in response to KCl incubation. The DNA
      methylation profile presented a very similar pattern in neuroectoderm gene
      promoters. CONCLUSIONS: Data indicate that there are no significant differences
      between the undifferentiated and supposedly neuronal-differentiated mesenchymal
      cells.

PMID- 24935042
TI  - Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces
      in vitro: a potential beneficial therapeutic effect.
AB  - AIM: Injury of tendons contained within a synovial environment, such as joint,
      bursa or tendon sheath, frequently fails to heal and releases matrix proteins
      into the synovial fluid, driving inflammation. This study investigated the
      effectiveness of cells to seal tendon surfaces and provoke matrix synthesis as a
      possible effective injectable therapy. MATERIALS & METHODS: Equine flexor tendon
      explants were cultured overnight in suspensions of bone marrow and synovium
      derived mesenchymal stems cells and, as controls, two sources of fibroblasts,
      derived from tendon and skin, which adhered to the explants. Release of the most
      abundant tendon extracellular matrix proteins into the media was assayed, along
      with specific matrix proteins synthesis by real-time PCR. RESULTS: Release of
      extracellular matrix proteins was influenced by the coating cell type.
      Fibroblasts from skin and tendon appeared less capable of preventing the release
      of matrix proteins than mesenchymal stems cells. CONCLUSION: The source of cell
      is an important consideration for cell therapy.

PMID- 24935044
TI  - Regulation of cell-based therapeutic products intended for human applications in
      the EU.
AB  - AIMS: Recent developments in the field of cell-based therapeutic products (CBTPs)
      have forced the EU to revise its legislation on therapeutic products by enacting
      several new legal instruments. In this study, we investigate how CBTPs are
      regulated and what determines their regulatory classification. Furthermore, we
      compare the regulatory burden between CBTPs in different product categories.
      MATERIALS & METHODS: Product categories covering CBTPs were identified and
      characteristics critical for the regulatory classification of a CBTP were
      determined in each category. The effect of the critical characteristics on the
      classification was evaluated by constructing a decision tree that covers all
      possible combinations of the critical characteristics. Differences in the
      regulatory burden between CBTPs were evaluated by comparing regulations crucial
      for placing a therapeutic product on the EU market between the product
      categories. RESULTS: Regulation of CBTPs has been divided between the main
      product categories of the EU legal framework for therapeutic products on the
      basis of the characteristics of the cells that the CBTPs contain. The regulatory
      burden is lowest for CBTPs regulated as blood, cells or tissues, and highest for
      CBTPs regulated as medicinal products. CONCLUSION: CBTPs exist in all product
      categories of the EU legal framework for therapeutic products. However, the
      current framework does not cover all possible CBTPs. Furthermore, our results
      indicate that the regulatory burden of a CBTP is related to the risk it may pose
      to the health and safety of recipients.

PMID- 24935043
TI  - Biomimetic fibrin-hyaluronan hydrogels for nucleus pulposus regeneration.
AB  - AIM: To develop a biomimetic polymeric injectable hydrogel that can support
      nucleus pulposus (NP) regeneration. MATERIALS & METHODS: Natural polymer-based
      hydrogels were synthesized using fibrinogen (FBG) and hyaluronic acid (HA),
      conjugated by a novel two-step procedure. Bovine NP cells were cultured in FBG-HA
      conjugate-based 3D beads in vitro and in a nucleotomized organ culture model.
      RESULTS: FBG-HA conjugate-based hydrogels prepared with 235 KDa HA at a FBG/HA
      w/w ratio of 17:1 showed superior gel stability and mechanical properties and
      markedly increased glycosaminoglycan synthesis compared with a FBG/HA mixture
      based hydrogels or fibrin gels. Gene-expression levels of NP markers were
      maintained in vitro. In organ culture, NP cells seeded in FBG-HA conjugate-based
      hydrogels showed better integration with native NP tissue compared with fibrin
      gels. Moreover, FBG-HA conjugate-based hydrogels restored compressive stiffness
      and disc height after nucleotomy under dynamic load. CONCLUSION: Specific FBG-HA
      conjugate-based hydrogels may be suitable as injectable materials for minimally
      invasive, biological NP regeneration.

PMID- 24935045
TI  - Health consumers and stem cell therapy innovation: markets, models and
      regulation.
AB  - Global health consumer demand for stem cell therapies is vibrant, but the supply
      of treatments from the conventional science-based model of innovation is small
      and unlikely to increase in the near future. At the same time, several models of
      medical innovation have emerged that can respond to the demand, often employing a
      transnational value chain to deliver the product. Much of the commentary has
      approached the issue from a supply side perspective, demonstrating the extent to
      which national and transnational regulation fails to impose what are regarded as
      appropriate standards on the 'illicit' supply of stem cell therapies
      characterized by little data and poor outcomes. By contrast, this article
      presents a political economic analysis with a strong demand side perspective,
      arguing that the problem of what is termed 'stem cell tourism' is embedded in the
      demand-supply relationship of the health consumer market and its engagement with
      different types of stem cell therapy innovation. To be meaningful, discussions of
      regulation must recognize that analysis or risk being sidelined by a market,
      which ignores their often wishful thinking. 

PMID- 24935046
TI  - Biologic scaffold for CNS repair.
AB  - Injury to the CNS typically results in significant morbidity and endogenous
      repair mechanisms are limited in their ability to restore fully functional CNS
      tissue. Biologic scaffolds composed of individual purified components have been
      shown to facilitate functional tissue reconstruction following CNS injury.
      Extracellular matrix scaffolds derived from mammalian tissues retain a number of
      bioactive molecules and their ability for CNS repair has recently been
      recognized. In addition, novel biomaterials for dural mater repairs are of
      clinical interest as the dura provides barrier function and maintains homeostasis
      to CNS. The present article describes the application of regenerative medicine
      principles to the CNS tissues and dural mater repair. While many approaches have
      been exploring the use of cells and/or therapeutic molecules, the strategies
      described herein focus upon the use of extracellular matrix scaffolds derived
      from mammalian tissues that are free of cells and exogenous factors. 

PMID- 24935047
TI  - Biodegradable elastomers for biomedical applications and regenerative medicine.
AB  - Synthetic biodegradable polymers are of great value for the preparation of
      implants that are required to reside only temporarily in the body. The use of
      biodegradable polymers obviates the need for a second surgery to remove the
      implant, which is the case when a nondegradable implant is used. After
      implantation in the body, biomedical devices may be subjected to degradation and
      erosion. Understanding the mechanisms of these processes is essential for the
      development of biomedical devices or implants with a specific function, for
      example, scaffolds for tissue-engineering applications. For the engineering and
      regeneration of soft tissues (e.g., blood vessels, cardiac muscle and peripheral
      nerves), biodegradable polymers are needed that are flexible and elastic. The
      scaffolds prepared from these polymers should have tuneable degradation
      properties and should perform well under long-term cyclic deformation conditions.
      The required polymers, which are either physically or chemically crosslinked
      biodegradable elastomers, are reviewed in this article. 

PMID- 24935049
TI  - Ultra widefield fundus imaging for diabetic retinopathy.
AB  - For decades, the standard method for screening and grading severity of diabetic
      retinal disease has relied upon a montage of photographs using normal angle
      fundus cameras. With the development of ultrawide field (UWF) fundus imaging,
      more of the retina can be imaged with fewer pictures, less dependence on
      photographer skill, and, often, greater ease on the patient. Recent studies have
      shown comparability between traditional and UWF imaging for standard grading of
      diabetic retinopathy. Moreover, UWF images can detect peripheral pathology not
      typically seen in standard photographs, which may enlighten our understanding of
      disease severity and suggest new indications for treatment.

PMID- 24935050
TI  - Natural language processing pipelines to annotate BioC collections with an
      application to the NCBI disease corpus.
AB  - BioC is a new format and associated code libraries for sharing text and
      annotations. We have implemented BioC natural language preprocessing pipelines in
      two popular programming languages: C++ and Java. The current implementations
      interface with the well-known MedPost and Stanford natural language processing
      tool sets. The pipeline functionality includes sentence segmentation,
      tokenization, part-of-speech tagging, lemmatization and sentence parsing. These
      pipelines can be easily integrated along with other BioC programs into any BioC
      compliant text mining systems. As an application, we converted the NCBI disease
      corpus to BioC format, and the pipelines have successfully run on this corpus to
      demonstrate their functionality. Code and data can be downloaded from
      http://bioc.sourceforge.net. Database URL: http://bioc.sourceforge.net. 

PMID- 24935051
TI  - Effects of calcium carbonate, sevelamer hydrochloride or pantoprazole on the
      pharmacokinetics of cinacalcet.
AB  - BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism is a common consequence
      of chronic kidney disease. Cinacalcet (Sensipar((r))) is often prescribed in
      combination to reduce elevated levels of parathyroid hormone, calcium and
      phosphorus. The objective of this study was to assess the effects of
      concomitantly administered therapies of calcium carbonate (CaCO(3); TUMS((r))),
      sevelamer hydrochloride (HCl; Renagel((r))) and pantoprazole sodium
      (Protonix((r))) on the pharmacokinetics and safety of cinacalcet in healthy
      subjects. METHODS: Three randomized, open-label, two-way crossover
      pharmacokinetic studies were conducted in healthy subjects. Participants received
      single doses of cinacalcet alone or in combination with either CaCO(3), sevelamer
      HCl or pantoprazole. The pharmacokinetic profile of cinacalcet was characterized.
      Safety assessments including adverse event reporting, changes in vital signs and
      clinical laboratory measurements were conducted throughout the studies. RESULTS:
      The 90 % confidence intervals for the area under the concentration-time curve
      from time zero to the last quantifiable concentration (AUC(last)), area under the
      concentration-time curve from time zero to infinity (AUC(0-infinity)) and maximum
      plasma concentration (C(max)) of cinacalcet were within the accepted range of 80
      125 % for both CaCO(3) and sevelamer HCl co-administration with cinacalcet. No
      severe or serious adverse events or clinically relevant changes in physical or
      laboratory findings occurred during the studies. CONCLUSION: The pharmacokinetic
      parameters of cinacalcet were not affected by co-administration of CaCO(3),
      sevelamer HCl or pantoprazole. Co-administration of these agents with cinacalcet
      does not require an adjustment of the dose of cinacalcet.

PMID- 24935052
TI  - Preliminary, open-label, pilot study of add-on oral Delta9-tetrahydrocannabinol
      in chronic post-traumatic stress disorder.
AB  - BACKGROUND AND OBJECTIVES: Many patients with post-traumatic stress disorder
      (PTSD) achieve but partial remission with current treatments. Patients with
      unremitted PTSD show high rates of substance abuse. Marijuana is often used as
      compassion add-on therapy for treatment-resistant PTSD. This open-label study
      evaluates the tolerance and safety of orally absorbable Delta(9)
      tetrahydrocannabinol (THC) for chronic PTSD. METHODS: Ten outpatients with
      chronic PTSD, on stable medication, received 5 mg of Delta(9)-THC twice a day as
      add-on treatment. RESULTS: There were mild adverse effects in three patients,
      none of which led to treatment discontinuation. The intervention caused a
      statistically significant improvement in global symptom severity, sleep quality,
      frequency of nightmares, and PTSD hyperarousal symptoms. CONCLUSIONS: Orally
      absorbable Delta(9)-THC was safe and well tolerated by patients with chronic
      PTSD.

PMID- 24935053
TI  - Accelerated MRI thermometry by direct estimation of temperature from undersampled
      k-space data.
AB  - PURPOSE: Acceleration of magnetic resonance (MR) thermometry is desirable for
      several applications of MR-guided focused ultrasound, such as those requiring
      greater volume coverage, higher spatial resolution, or higher frame rates.
      METHODS: We propose and validate a constrained reconstruction method that
      estimates focal temperature changes directly from k-space without spatial or
      temporal regularization. A model comprising fully-sampled baseline images is fit
      to undersampled k-space data, which removes aliased temperature maps from the
      solution space. Reconstructed temperature maps are compared to maps reconstructed
      using parallel imaging (iterative self-consistent parallel imaging reconstruction
      [SPIRiT]) and conventional hybrid thermometry, and temporally constrained
      reconstruction thermometry. RESULTS: Temporal step response simulations
      demonstrate finer temporal resolution and lower error in 4*-undersampled radial k
      space reconstructions compared to temporally constrained reconstruction.
      Simulations show that the k-space method can achieve higher accelerations with
      multiple receive coils. Phantom heating experiments further demonstrate the
      algorithm's advantage over reconstructions relying on parallel imaging alone to
      overcome undersampling artifacts. In vivo model error comparisons show the
      algorithm achieves low temperature error at higher acceleration factors (up to
      32* with a radial trajectory) than compared reconstructions. CONCLUSION: High
      acceleration factors can be achieved using the proposed temperature
      reconstruction algorithm, without sacrificing temporal resolution or accuracy.

PMID- 24935054
TI  - Design, synthesis, and fungicidal activity of novel carboxylic acid amides
      represented by N-benzhydryl valinamode carbamates.
AB  - Carboxylic acid amide (CAA) fungicides are an important class of agricultural
      fungicide with oomycete activity and low toxicity toward mammalian cells. To find
      CAA analogues with high activity against resistant pathogens, a series of
      substituted N-benzhydryl valinamide carbamate derivatives were designed and
      synthesized by introducing substituted aromatic rings into valinamide carbamate
      leads. Bioassays showed that some title compounds exhibited very good in vitro
      fungicidal activity against Phytophthora capsici and in vivo fungicidal
      activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to
      explore the structure-activity relationship on the basis of the in vitro data.
      The dimethoxy substituted aromatic analogue 9e was found to display higher in
      vitro fungicidal activity against Phytophthora capsici than iprovalicarb but
      lower activity than mandipropamid, and higher in vivo fungicidal activity against
      Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 MUg mL(-1).

PMID- 24935055
TI  - Spin-glass-like dynamics of ferromagnetic clusters in La(0.75)Ba(0.25)CoO3.
AB  - We report a magnetization study of the compound La0.75Ba0.25CoO3 where the Ba(2+)
      doping is just above the critical limit for percolation of ferromagnetic
      clusters. The field cooled and zero-field cooled (ZFC) magnetization exhibit
      thermomagnetic irreversibility and the ac susceptibility shows a frequency
      dependent peak at the ferromagnetic ordering temperature (TC ~ 203 K) of the
      clusters. These features indicate the presence of a non-equilibrium state below
      TC. For the non-equilibrium state, the dynamic scaling of the imaginary part of
      the ac susceptibility and the static scaling of the nonlinear susceptibility
      clearly establish a spin-glass-like cooperative freezing of ferromagnetic
      clusters at 200.9(2) K. The assertion of the occurrence of spin-glass-like
      freezing of ferromagnetic clusters is further substantiated by ZFC ageing and
      memory experiments. We also observe certain dynamical features which are not
      present in a typical spin glass, such as: the initial magnetization after ZFC
      ageing first increases and then decreases with the waiting time; and there is an
      imperfect recovery of relaxation in negative temperature cycling experiments.
      This imperfect recovery transforms to perfect recovery for concurrent field
      cycling. Our analysis suggests that these additional dynamical features have
      their origin in the inter-cluster exchange interaction and cluster size
      distribution. The inter-cluster exchange interaction above the magnetic
      percolation level gives a superferromagnetic state in some granular thin films,
      but our results show the absence of a typical superferromagnetic-like state in
      La0.75Ba0.25CoO3. 

PMID- 24935056
TI  - Reduction of hyperproduction of thyroid autoantibodies in patients without
      disturbance of the thyroid function: new patents.
AB  - A new method of reduction of autoimmune process activity related to the thyroid
      in patients without signs of thyroiditis is presented in the article (patent of
      Ukraine No. 103742). New patents and inventions from different countries of the
      world related to the problem have been analysed. MATERIALS AND METHODS: Sixty one
      patients with a significant disturbance of tolerance to the thyroid antigens in
      the absence of disturbance of the thyroid function were involved in the research.
      Twenty two patients with chronic hepatitis C, genotype 1 HCV, receiving antiviral
      therapy, were also included in the research. Patients were immunized
      intracutaneously with autoleukocytes for autoimmune process inhibition. After
      single immunization with autoleukocytes decrease in the level of antibodies
      against the thyroid antigens was observed in all patients. In some patients
      without chronic hepatitis C the levels of thyroperoxidase and thyroglobulin
      antibodies decreased by 50% and more (33.33% and 20.51%, respectively). In
      patients with ChHC these indices were considerably lower, and the duration of the
      achieved effect was shorter. However, immunization inhibited activity of immune
      process in patients with ChHC due to interferon therapy. The suggested method
      enables to decrease the threat for thyroiditis development even in patients with
      chronic hepatitis C during antiviral therapy.

PMID- 24935057
TI  - Microscopic gastrointestinal stromal tumors in the gastric antrum--reply.

PMID- 24935058
TI  - Severe enterocolitis associated with antiepileptic-induced drug reaction with
      eosinophilia and systemic symptoms.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but
      serious drug-induced reaction with cutaneous, hematologic, and solid-organ
      injury. Antiepileptic drugs are one of the most common classes of drugs
      implicated in DRESS. A high morbidity and mortality may result, especially if the
      offending drug is not withdrawn promptly. Although DRESS may involve many organs,
      severe involvement of the gastrointestinal tract in DRESS and/or in association
      with antiepileptic drugs has rarely been reported. We report detailed clinical
      and histopathologic findings of a fatal case of DRESS syndrome resulting from
      antiepileptic drug treatment that was accompanied by severe enterocolitis,
      malabsorption, and cachexia. 

PMID- 24935060
TI  - Microscopic gastrointestinal stromal tumors in the gastric antrum.

PMID- 24935059
TI  - Intermediate serrated polyp as an intermediate lesion of hyperplastic polyp and
      sessile serrated polyp/adenoma in terms of morphological and molecular features.
AB  - Although a hyperplastic polyp (HP) shares morphological and molecular features
      with a sessile serrated adenoma/polyp (SSA/P), HPs and SSA/Ps are considered
      nonneoplastic and neoplastic epithelial polyps, respectively. Because HPs and
      SSA/Ps cover the morphological spectrum, we hypothesized that an intermediate
      serrated polyp (ISP) might exist between an HP and an SSA/P in terms of both
      morphological and molecular aspects. An ISP was defined as a serrated lesion that
      carries distorted crypts (columnar crypt dilation, irregularly branching crypts,
      or horizontally arranged basal crypts) in less than 3 consecutive crypts. We
      analyzed HPs (microvesicular, n = 16, and goblet cell-rich, n = 28), ISPs (n =
      44), and SSA/Ps (n = 26) for their methylation status of 8 CpG island methylator
      phenotype panel markers and mutation status of KRAS/BRAF. The number of
      methylated markers and BRAF mutation frequency increased in the order of HP, ISP,
      and SSA/P. Microvesicular HPs and goblet cell-rich HPs are distinct from each
      other, based on the high frequency of BRAF and KRAS mutation, respectively, but
      are not different in the number of methylated panel markers. Proximally located
      microvesicular HPs and ISPs were higher in the number of methylated markers but
      lower in the frequency of BRAF mutation than distally located ones. However,
      SSA/Ps did not show any difference in the number of methylated markers and the
      frequency of BRAF mutation between proximally and distally located lesions. Our
      findings that serrated polyps, intermediate between HPs and SSA/Ps in terms of
      morphological features, display molecular alterations intermediate between those
      of HPs and SSA/Ps suggest the presence of ISPs between HPs and SSA/Ps. 

PMID- 24935061
TI  - An evaluation of Congo red fluorescence for the diagnosis of amyloidosis.
AB  - Congo red stain apple-green birefringence under polarized light is the most
      popular method for detecting amyloid; however, it has limitations. The goal of
      this study was to evaluate if examination of Congo red stain by fluorescent
      microscopy (FM) significantly enhances the diagnostic yield. Congo red-stained
      tissue sections were retrospectively and prospectively examined by light
      microscopy (LM) with and without polarizer and by FM using the Texas red filter
      and results by each method compared. Congo red-stained amyloid recognized by LM
      was unequivocally and easily identified by FM in each of 48 cases. In 22 of them,
      FM either confirmed the presence of a small amount of amyloid or lead to a
      definitive diagnosis, which was otherwise missed. Eight cases with Congo red
      negative by LM were also negative by FM. In 8 cases with a false-positive Congo
      red stain, FM still detected the signal in 5, but it was absent in 3 cases. In
      conclusion, Congo red fluorescence improves the diagnostic yield of LM for both
      positive and negative cases. 

PMID- 24935062
TI  - Expression of high-mobility group AT-hook protein 2 and its prognostic
      significance in malignant gliomas.
AB  - High-mobility group AT-hook protein 2 (HMGA2) is an architectural transcription
      factor associated with malignancy, invasiveness, and poor prognosis in a variety
      of human neoplasms. This study investigated HMGA2 expression and prognostic value
      in human gliomas. We also correlated HMGA2 expression with Ki-67 labeling index
      and matrix metalloproteinase-2. Expression of HMGA2 in 78 human gliomas and 7
      human normal brain samples was studied using immunohistochemistry, and 29 gliomas
      were randomly selected and studied along with the normal brain by real-time
      quantitative polymerase chain reaction and Western blot analysis. Expression of
      HMGA2 protein was significantly higher in glioblastoma multiforme (World Health
      Organization [WHO] grade IV; P = .007) and anaplastic astrocytoma (WHO grade III;
      P = .037) than in diffuse astrocytoma (WHO grade II). Expression of HMGA2
      correlated significantly with expression of Ki-67 (r = 0.415, P < .01) and matrix
      metalloproteinase-2 (r = 0.363, P < .01), but not with patient sex and age. The
      real-time quantitative polymerase chain reaction and Western blot analysis
      revealed similar results. Patients with tumors expressing HMGA2 at a higher level
      had a significantly shorter progression-free survival time (11.2 months versus
      18.8 months; P = .021). Expression of HMGA2 significantly correlates with tumor
      cell proliferation, invasion, and survival in gliomas. The results suggest that
      HMGA2 has an important role in the treatment and prognosis of these cancers.

PMID- 24935063
TI  - Clinical aspects of hysteroscopic diagnosis of atypical endometrial hyperplasia.

PMID- 24935064
TI  - Association of Carotid Intima-media Thickness and Atherosclerotic Plaque with
      Periodontal Status.
AB  - Studies have suggested an association between clinical/subclinical
      atherosclerosis and periodontal status. The purpose of this study was to
      investigate the association among maximal carotid intima-media thickness (cIMT),
      atherosclerotic plaque, and periodontal status in Chinese elderly patients. A
      cross-sectional study was conducted of 847 participants (age, 70.64 +/- 9.03 yr)
      with >=10 teeth. A questionnaire survey, routine biochemical tests, a periodontal
      examination, and maximal cIMT measurement were performed for each. Traditional
      risk factors for atherogenesis were considered in the statistical analysis. Mean
      plaque index, which reflects oral hygiene, was correlated with maximal cIMT and
      atherosclerotic plaque in the study sample overall (beta = 0.068, p < .001; OR =
      2.051, p < .001) and in euglycemic participants (beta = 0.066, p = .008; odds
      ratio = 2.122, p = .009). In hyperglycemic participants, multiple linear
      regression analysis (p = .006) and multivariate logistic regression analysis (p =
      .025) revealed a linear and dose-dependent association between mean clinical
      attachment loss and maximal cIMT after adjustment for traditional risk factors.
      Each 1-mm increase in mean clinical attachment loss corresponded to a 0.018-mm
      increase in maximal cIMT. The risk of atherosclerotic plaque increased by 18.3%
      with each 1-mm increase in mean clinical attachment loss. Other indicators of
      periodontal exposure, including percentage of sites with attachment loss >= 3 to
      5 mm (3%-5%), were also correlated with cIMT and atherosclerotic plaque in
      hyperglycemic patients. In this elderly population, a linear and dose-dependent
      association among mean clinical attachment loss, attachment loss 3% to 5%,
      maximal cIMT, and atherosclerotic plaque was verified in those with
      hyperglycemia. Poor oral hygiene was correlated with maximal cIMT and
      atherosclerotic plaque in all participants, including those with normal blood
      glucose. 

PMID- 24935065
TI  - Addition of Grape Seed Extract Renders Phosphoric Acid a Collagen-stabilizing
      Etchant.
AB  - Previous studies found that grape seed extract (GSE), which is rich in
      proanthocyanidins, could protect demineralized dentin collagen from
      collagenolytic activities following clinically relevant treatment. Because of
      proanthocyanidin's adverse interference to resin polymerization, it was believed
      that GSE should be applied and then rinsed off in a separate step, which in
      effect increases the complexity of the bonding procedure. The present study aimed
      to investigate the feasibility of combining GSE treatment with phosphoric acid
      etching to address the issue. It is also the first attempt to formulate collagen
      cross-linking dental etchants. Based on Fourier-transformed infrared spectroscopy
      and digestion assay, it was established that in the presence of 20% to 5%
      phosphoric acid, 30 sec of GSE treatment rendered demineralized dentin collagen
      inert to bacterial collagenase digestion. Based on this positive result, the
      simultaneous dentin etching and collagen protecting of GSE-containing phosphoric
      acid was evaluated on the premise of a 30-second etching time. According to micro
      Raman spectroscopy, the formulation containing 20% phosphoric acid was found to
      lead to overetching. Based on scanning and transmission electronic microscopy,
      this same formulation exhibited unsynchronized phosphoric acid and GSE
      penetration. Therefore, addition of GSE did render phosphoric acid a collagen
      stabilizing etchant, but the preferable phosphoric acid concentration should be
      <20%. 

PMID- 24935066
TI  - MMP Inhibitors on Dentin Stability: A Systematic Review and Meta-analysis.
AB  - The aim of this study was to systematically review the literature for in vitro
      and ex vivo studies that evaluated the effect of matrix metalloproteinase (MMP)
      inhibitors during the adhesive procedure on the immediate and long-term resin
      dentin bond strength. The search was conducted in 6 databases with no publication
      year or language limits, following the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) statement. From 1,336 potentially eligible
      studies, 48 were selected for full-text analysis, and 30 were included for
      review, with 17 considered in the meta-analysis. Two reviewers independently
      selected the studies, extracted the data, and assessed the risk of bias. Pooled
      effect estimates were expressed as the weighted mean difference between groups.
      The most used MMP inhibitor was chlorhexidine (CHX). Immediate bond strength
      results showed no difference between 2% CHX and control; however, a difference
      was found between 0.2% CHX and control at baseline. After aging, CHX presented
      higher bond strength values compared to control groups (p < .05). However, this
      was not observed for longer periods of aging. High heterogeneity was found in
      some comparisons, especially for the water storage aging subgroup. Subgroup
      analyses showed that self-etching and etch-and-rinse adhesives are benefited by
      the CHX use. From the studies included, only 1 presented low risk of bias, while
      the others showed medium or high risk of bias. The use of MMP inhibitors did not
      affect the immediate bond strength overall, while it influenced the aged bond
      strength. Aging procedures influenced bond strength values of the dentin adhesion
      stability. 

PMID- 24935067
TI  - Impact of the Oral Commensal Flora on Alveolar Bone Homeostasis.
AB  - Homeostasis of healthy periodontal tissues is affected by innate and adaptive
      immunosurveillance mechanisms in response to the normal oral flora. Recent
      comparisons of germ-free (GF) and normal specific-pathogen-free (SPF) mice have
      revealed the impact of host immunosurveillance mechanisms in response to the
      normal oral flora on alveolar bone height. Prior reports that alveolar bone
      height is significantly less in normal SPF mice compared with their age- and
      strain-matched GF counterparts suggest that naturally occurring alveolar bone
      loss is a normal component of healthy periodontal tissue homeostasis. In this
      report, histomorphometric analyses confirmed increased alveolar bone loss and
      revealed increased numbers of TRAP+ osteoclastic cells lining the alveolar bone
      surface in SPF compared with GF mice. Increased numbers of RANKL+ cells and IL17+
      cells in the periodontium of SPF mice demonstrate possible molecular mechanisms
      mediating the up-regulated osteoclastogenesis and alveolar bone loss in SPF mice
      compared with GF mice. Increased numbers of T-lymphocytic cells and T-helper
      cells in the junctional epithelium of SPF mice compared with GF mice suggest that
      the adaptive immune response contributes to physiologic alveolar bone loss in the
      healthy periodontium. This GF animal model study notably begins to elucidate the
      impact of host immunosurveillance mechanisms in response to the normal oral
      flora, mediating catabolic alveolar bone homeostasis in the healthy periodontium.

PMID- 24935068
TI  - Efficacy and safety of flurbiprofen axetil in the prevention of pain on propofol
      injection: a systematic review and meta-analysis.
AB  - BACKGROUND: Pain on injection is an acknowledged adverse effect (AE) of propofol
      administration for the induction of general anesthesia. Flurbiprofen axetil has
      been reported to reduce the pain of injection. However, results of published
      papers on the efficacy of flurbiprofen axetil in managing pain on injection of
      propofol are inconsistent. MATERIAL/METHODS: We conducted a comprehensive meta
      analysis of studies to appraise the efficacy and safety of flurbiprofen axetil
      for controlling pain induced by propofol injection. The pooled risk ratio (RR)
      with corresponding 95% confidence intervals (CI) was calculated employing fixed-
      or random-effects models, depending upon the heterogeneity of the included
      trials. RESULTS: Compared with the placebo group, flurbiprofen axetil allows more
      patients to have no pain (RR 3.51, 95% CI 2.22-5.55, p=0.000), and decreases the
      cumulative number of patients with mild, moderate, and severe pain on injecting
      propofol (RR 0.70, 95% CI 0.58-0.86, p=0.000; RR 0.59, 95% CI 0.46-0.75, p=0.000;
      RR 0.25, 95% CI 0.16-0.38, p=0.000, respectively). In the stratified analysis by
      the doses, flurbiprofen axetil at a dose of over 50 mg was found to be effective
      in reducing propofol-induced pain on injection; however, there were no
      significant differences in relieving pain between treatment and placebo groups
      with flurbiprofen axetil at a dose of 25 mg. In terms of drug safety, there were
      no adverse effects (AEs) reported between flurbiprofen axetil-based regimens and
      placebo regimens. CONCLUSIONS: Flurbiprofen axetil, an injectable prodrug of
      flurbiprofen, can significantly prevent or relieve the pain induced by propofol
      injection. More studies are required to assess its adverse effects.

PMID- 24935069
TI  - Identifying qualitative effects of different grazing types on below-ground
      communities and function in a long-term field experiment.
AB  - Herbivory is an important modulator of plant biodiversity and productivity in
      grasslands, but our understanding of herbivore-induced changes on below-ground
      processes and communities is limited. Using a long-term (17 years) experimental
      site, we evaluated impacts of rabbit and invertebrate grazers on some soil
      functions involved in carbon cycling, microbial diversity, structure and
      functional composition. Both rabbit and invertebrate grazing impacted soil
      functions and microbial community structure. All functional community measures
      (functions, biogeochemical cycling genes, network association between different
      taxa) were more strongly affected by invertebrate grazers than rabbits.
      Furthermore, our results suggest that exclusion of invertebrate grazers decreases
      both microbial biomass and abundance of genes associated with key biogeochemical
      cycles, and could thus have long-term consequences for ecosystem functions. The
      mechanism behind these impacts are likely to be driven by both direct effects of
      grazing altering the pattern of nutrient inputs and by indirect effects through
      changes in plant species composition. However, we could not entirely discount
      that the pesticide used to exclude invertebrates may have affected some microbial
      community measures. Nevertheless, our work illustrates that human activity that
      affects grazing intensity may affect ecosystem functioning and sustainability, as
      regulated by multi-trophic interactions between above- and below-ground
      communities. 

PMID- 24935070
TI  - An overall characterization of pediatric acute lymphoblastic leukemia with CRLF2
      overexpression.
AB  - For an overall characterization of pediatric B-cell precursor acute lymphoblastic
      leukemia (BCPALL) with CRLF2 overexpression (OE), we conducted genetic analysis
      of CRLF2 in 167 pediatric BCPALL patients. CRLF2 OE was detected in 30 (18%) of
      167 patients, the P2RY8-CRLF2 fusion was identified in only 3 (1.8%) of 167
      patients, all of which demonstrated CRLF2 OE. Moreover, CRLF2 gain was identified
      in 18 (11%) of 167 patients. Messenger RNA sequencing revealed a novel fusion
      transcript, CSF2RA-CRLF2, in a case with CRLF2 OE, suggesting that this fusion is
      associated with CRLF2 OE. In survival analysis, no significant differences in 5
      year event-free survival (EFS) and overall survival were observed between
      patients with and without CRLF2 OE (70.7 vs. 75.4%, log rank P = 0.68 and 96.4
      vs. 82.1%, log rank P = 0.11, respectively). However, a significant difference in
      5-year EFS between CRLF2 OE patients with and without IKZF1 deletion was observed
      (44.4 vs. 83.1%, log rank P = 0.02). In multivariate analysis, only IKZF1
      deletion was a significant predictor of inferior OS (hazard ratio: 2.427, P =
      0.04).These findings suggest that CRLF2 OE is not an independent prognostic
      factor in pediatric BCPALL.

PMID- 24935071
TI  - Subclavian artery intervention with a balloon-tipped occlusion catheter via the
      ipsilateral brachial artery without an introducer sheath.
AB  - To protect against a distal embolism in the vertebral artery, subclavian artery
      stenting can be achieved by positioning a filter device or balloon in the
      ipsilateral vertebral artery. However, treatment with these devices is not easy,
      and it is also an inaccurate method for cerebral protection. We developed a
      balloon-tipped occlusion catheter (Optimo((r)) occlusion catheter) without an
      introducer sheath, which allowed us to perform the minimally invasive
      endovascular therapy (EVT). Herein, we report two EVT cases for subclavian artery
      disease treated with an Optimo((r)) occlusion catheter via the ipsilateral
      brachial artery. This method is effective for distal protection of both cerebral
      and brachial artery embolism, and also enables EVT procedure retrogradely as
      well. 

PMID- 24935072
TI  - Pharmacodynamics, pharmacokinetics and safety of ticagrelor in Asian patients
      with stable coronary artery disease.
AB  - This randomized, active-controlled, double-blind study assessed the
      pharmacodynamics, pharmacokinetics and safety of ticagrelor in Japanese patients
      and a smaller cohort of non-Japanese Asian patients. The study recruited patients
      aged 20-80 years who had received aspirin 75-100 mg/day for >=2 weeks and had
      percutaneous coronary intervention or acute coronary syndrome >3 months
      previously. Patients received 4 weeks' treatment with ticagrelor 45 mg bid,
      ticagrelor 90 mg bid or clopidogrel 75 mg qd (all with aspirin). The inhibition
      of platelet aggregation (IPA, final-extent) and pharmacokinetics of ticagrelor
      were assessed on days 1 and 28. Overall, 139 Asian patients were randomized
      (ticagrelor 45 mg bid, n = 50; ticagrelor 90 mg bid, n = 43; clopidogrel, n = 46)
      of whom 118 were Japanese. Mean final-extent IPA was greater with ticagrelor 90
      mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus
      clopidogrel. At the end of the dosing interval on day 28, mean final-extent IPA
      was 10.0% higher (95% confidence interval 0.5-19.5%) for ticagrelor 90 mg bid
      versus ticagrelor 45 mg bid, 15.1% higher (5.8-24.4%) for ticagrelor 45 mg bid
      versus clopidogrel, and 25.1% higher (15.5-34.7%) for ticagrelor 90 mg bid versus
      clopidogrel. In Japanese patients, exposure to ticagrelor and its active
      metabolite AR-C124910XX increased dose-proportionally. The safety profile of
      ticagrelor was consistent with previous studies. Ticagrelor was associated with
      enhanced IPA versus clopidogrel in Japanese patients.

PMID- 24935073
TI  - You've received a complaint: what next?

PMID- 24935074
TI  - ACR appropriateness criteria management of vertebral compression fractures.
AB  - This is an updated review of management of vertebral compression fracture for
      both benign osteoporotic and malignant causes. Vertebral compression fracture
      radiologic imaging evaluation is discussed. A literature review is provided of
      current indications for vertebral augmentation with percutaneous vertebroplasty
      and kyphoplasty as well as medical management. Limitations and potential benefits
      of these procedures are discussed. Variant tables describing various clinical
      situations are also provided to assist in determining appropriate use of these
      treatments for patient care. The ACR Appropriateness Criteria are evidence-based
      guidelines for specific clinical conditions that are reviewed every 3 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 formulate recommendations for imaging or treatment. 

PMID- 24935075
TI  - Senior work-up assessment and treatment team in an emergency department: a
      randomised control trial.
AB  - OBJECTIVE: To evaluate the impact of a senior early assessment model of care on
      performance measures in a single ED. METHODS: A pragmatic single-blinded
      randomised control trial with day of ED presentation randomised to one of three
      study arms: senior work-up assessment and treatment (SWAT) model of care
      intervention, non-SWAT control or control. PRIMARY OUTCOME: The primary outcomes
      were the proportion of patients meeting National Emergency Access Target (NEAT)
      criteria (ED length of stay less than 4 h) and ED length of stay. Secondary
      outcome measured was time to decision to admit in the subgroup of admitted
      patients. RESULTS: A total of 1737 patients were analysed. There was no overall
      difference in NEAT performance (48% [95% CI 44, 51] vs 41% ([95% CI 37, 45] vs
      46% [95% CI 41, 50], P = 0.09) or ED length of stay (P = 0.65) between SWAT, non
      SWAT and standard of care control groups, respectively. In the subgroup of
      patients discharged from ED (non-admitted), the SWAT intervention group was
      associated with higher NEAT performance (P = 0.004) compared with non-SWAT and
      control. CONCLUSION: A senior early assessment model of care was not associated
      with improved overall NEAT performance and ED length of stay. However, there is
      evidence that improvements were made in the subgroup of discharged patients.
      There was no difference in overall NEAT performance among the three study groups.

PMID- 24935076
TI  - Gene copy number alterations in the azoospermia-associated AZFc region and their
      effect on spermatogenic impairment.
AB  - The azoospermia factor c (AZFc) region in the long arm of human Y chromosome is
      characterized by massive palindromes. It harbors eight multi-copy gene families
      that are expressed exclusively or predominantly in testis. To assess
      systematically the role of the AZFc region and these eight gene families in
      spermatogenesis, we conducted a comprehensive molecular analysis (including Y
      chromosome haplogrouping, AZFc deletion typing and gene copy quantification) in
      654 idiopathic infertile men and 781 healthy controls in a Han Chinese
      population. The b2/b3 partial deletion (including both deletion-only and deletion
      duplication) was consistently associated with spermatogenic impairment. In the
      subjects without partial AZFc deletions, a notable finding was that the frequency
      of DAZ and/or BPY2 copy number alterations in the infertile group was
      significantly higher than in the controls. Combined patterns of DAZ and/or BPY2
      copy number abnormality were associated with spermatogenic impairment when
      compared with the pattern of all AZFc genes with common level copies. In
      addition, in Y chromosome haplogroup O1 (Y-hg O1), the frequency of copy number
      alterations of all eight gene families was significantly higher in the case group
      than that in the control group. Our findings indicate that the DAZ, BPY2 genes
      may be prominent players in spermatogenesis, and genomic rearrangements may be
      enriched in individuals belonging to Y-hg O1. Our findings emphasize the
      necessity of routine molecular analysis of AZFc structural variation during the
      workup of azoospermia and/or oligozoospermia, which may diminish the genetic risk
      of assisted reproduction. 

PMID- 24935079
TI  - Effect of negative pressure wound therapy on wound healing.
AB  - The efficacy of NPWT in promoting wound healing has been largely accepted by
      clinicians, yet the number of high-level clinical studies demonstrating its
      effectiveness is small and much more can be learned about the mechanisms of
      action. In the future, hopefully we will have the data to assist clinicians in
      selecting optimal parameters for specific wounds including interface material,
      waveform of suction application, and the amount of suction to be applied. Further
      investigation into specific interface coatings and instillation therapy are also
      needed. We believe that advances in mechanobiology, the science of wound healing,
      the understanding of biofilms, and advances in cell therapy will lead to better
      care for our patients.

PMID- 24935080
TI  - Impaired function of CD19(+) CD24(hi) CD38(hi) regulatory B cells in patients
      with pemphigus.
AB  - BACKGROUND: Pemphigus is an organ-specific autoimmune bullous disease.
      OBJECTIVES: To determine the role of regulatory B cells (Bregs) in patients with
      pemphigus. METHODS: The frequency of the occurrence of CD19(+) CD24(hi) CD38(hi)
      Bregs was detected from 34 patients with pemphigus and 20 healthy controls.
      Interleukin (IL)-10 secretion was processed after stimulating B cells. Specific
      antidesmoglein antibody (Ab) titres and their subclasses were also measured. Ab
      response and cytokine production from peripheral blood mononuclear cells (PBMCs)
      with or without Bregs were analysed. RESULTS: The number of Bregs was
      significantly increased in patients with pemphigus compared with healthy controls
      (15 +/- 7% vs. 9 +/- 3%; P < 0.01) and the proportion of Bregs in the active
      groups (newly diagnosed and chronic active patients) was significantly higher
      than in remittent individuals (16 +/- 7% vs. 13 +/- 8%; P = 0.04). The IL-10
      producing B cells were significantly increased upon stimulation both in patients
      and in healthy controls. However, the increase ratio of IL-10-producing B cells
      between short- and long-term stimulation was significantly lower in patients with
      pemphigus (1.0-fold vs. 2.6-fold increase in control group; P < 0.01).
      Strikingly, Bregs from the controls were able to suppress interferon (IFN)-gamma
      expression and T helper cell 1 (Th1) immune response (26% inhibition rate), while
      the suppressive function of Bregs from patients with pemphigus was significantly
      decreased (9% inhibition rate). There was no difference in Ab levels from PBMCs
      with or without Bregs after stimulation. CONCLUSIONS: Bregs in patients with
      pemphigus are elevated but with defective regulatory function on Th1 cells.

PMID- 24935081
TI  - Home-based family intervention increases knowledge, communication and living
      donation rates: a randomized controlled trial.
AB  - Our aim was to develop and test an educational program to support well-informed
      decision making among patients and their social network regarding living donor
      kidney transplantation (LDKT). One hundred sixty-three patients who were unable
      to find a living donor were randomized to standard care or standard care plus
      home-based education. In the education condition, patients and members of their
      social network participated in home-based educational meetings and discussed
      renal replacement therapy options. Patients and invitees completed pre-post self
      report questionnaires measuring knowledge, risk perception, communication, self
      efficacy and subjective norm. LDKT activities were observed for 6 months
      postintervention. Patients in the experimental group showed significantly more
      improvements in knowledge (p < 0.001) and communication (p = 0.012) compared with
      the control group. The invitees showed pre-post increases in knowledge (p <
      0.001), attitude toward discussing renal replacement therapies (p = 0.020),
      attitude toward donating a kidney (p = 0.023) and willingness to donate a kidney
      (p = 0.039) and a decrease in risk perception (p = 0.003). Finally, there were
      significantly more inquiries (29/39 vs. 13/41, p < 0.001), evaluations (25/39 vs.
      7/41, p < 0.001) and actual LDKTs (17/39 vs. 4/41, p = 0.003) in the experimental
      group compared with the control group. Home-based family education supports well
      informed decision making and promotes access to LDKT. 

PMID- 24935082
TI  - Sequential treatment with fluoxetine and relapse--prevention CBT to improve
      outcomes in pediatric depression.
AB  - OBJECTIVE: The authors evaluated a sequential treatment strategy of fluoxetine
      and relapse-prevention cognitive-behavioral therapy (CBT) to determine effects on
      remission and relapse in youths with major depressive disorder. METHOD: Youths 8
      17 years of age with major depression were treated openly with fluoxetine for 6
      weeks. Those with an adequate response (defined as a reduction of 50% or more on
      the Children's Depression Rating Scale-Revised [CDRS-R]) were randomly assigned
      to receive continued medication management alone or continued medication
      management plus CBT for an additional 6 months. The CBT was modified to address
      residual symptoms and was supplemented by well-being therapy. Primary outcome
      measures were time to remission (with remission defined as a CDRS-R score of 28
      or less) and rate of relapse (with relapse defined as either a CDRS-R score of 40
      or more with a history of 2 weeks of symptom worsening, or clinical
      deterioration). RESULTS: Of the 200 participants enrolled in acute-phase
      treatment, 144 were assigned to continuation treatment with medication management
      alone (N=69) or medication management plus CBT (N=75). During the 30-week
      continuation treatment period, time to remission did not differ significantly
      between treatment groups (hazard ratio=1.26, 95% CI=0.87, 1.82). However, the
      medication management plus CBT group had a significantly lower risk of relapse
      than the medication management only group (hazard ratio=0.31, 95% CI=0.13, 0.75).
      The estimated probability of relapse by week 30 was lower with medication
      management plus CBT than with medication management only (9% compared with
      26.5%). CONCLUSIONS: Continuation-phase relapse-prevention CBT was effective in
      reducing the risk of relapse but not in accelerating time to remission in
      children and adolescents with major depressive disorder.

PMID- 24935083
TI  - Clinical features, genetics, and outcome of pediatric patients with
      hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from
      Korea Histiocytosis Working Party.
AB  - BACKGROUND: We analyzed a nationwide registry of pediatric patients with
      hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and
      genetic features and treatment outcomes in pediatric HLH. METHODS: The Korea
      Histiocytosis Working Party retrospectively analyzed data on 251 pediatric
      patients diagnosed with HLH between 1996 and 2011. RESULTS: In the study cohort,
      25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and
      162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant
      Epstein-Barr virus infection. Of 238 evaluable patients, central nervous system
      (CNS) involvement, which was more frequent in the familial group, was evident in
      81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high
      incidence of two recurrent splicing mutations (c.118-308C>T and c.754-1G>C). The
      5-yr overall survival rate was 68% (38% in the familial group and 81% in the
      presumed secondary group). The 5-yr overall survival rate among 32 patients who
      underwent allogeneic hematopoietic stem cell transplantation was 64%. In
      multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a
      coagulation abnormality were independent prognostic factors for survival.
      Responses during initial treatments were also significant indicators of outcome.
      CONCLUSION: Our study showed the unique predominance of a UNC13D mutation and
      vulnerability to Epstein-Barr virus infection in Korean children with HLH and
      emphasizes the prognostic significance of age, liver dysfunction, and treatment
      responses in this disease. A multicenter prospective trial that builds on the
      present results is warranted to identify subgroups of patients with a poor
      prognosis and identify optimal treatments.

PMID- 24935084
TI  - Temporally unstructured electrical stimulation to the amygdala suppresses
      behavioral chronic seizures of the pilocarpine animal model.
AB  - Electrical stimulation applied to the basolateral amygdala in the
      pentylenetetrazole animal model of seizures may result in either a proconvulsant
      or an anticonvulsant effect depending on the interpulse intervals used: periodic
      or nonperiodic, respectively. We tested the effect of this electrical stimulation
      temporal coding on the spontaneous and recurrent behavioral seizures produced in
      the chronic phase of the pilocarpine animal model of temporal lobe epilepsy, an
      experimental protocol that better mimics the human condition. After 45 days of
      the pilocarpine-induced status epilepticus, male Wistar rats were submitted to a
      surgical procedure for the implantation of a bipolar electrical stimulation
      electrode in the right basolateral amygdala and were allowed to recover for seven
      days. The animals were then placed in a glass box, and their behaviors were
      recorded daily on DVD for 6h for 4 consecutive days (control period). Spontaneous
      recurrent behavioral seizures when showed in animals were further recorded for an
      extra 4-day period (treatment period), under periodic or nonperiodic electrical
      stimulation. The number, duration, and severity of seizures (according to the
      modified Racine's scale) during treatment were compared with those during the
      control period. The nonperiodically stimulated group displayed a significantly
      reduced total number and duration of seizures. There was no difference between
      control and treatment periods for the periodically stimulated group. Results
      corroborate previous findings from our group showing that nonperiodic electrical
      stimulation has a robust anticonvulsant property. In addition, results from the
      pilocarpine animal model further strengthen nonperiodic electrical stimulation as
      a valid therapeutic approach in current medical practice. Our working hypothesis
      is that temporally unstructured electrical stimulation may wield its effect by
      desynchronizing neural networks involved in the ictogenic process.

PMID- 24935085
TI  - "Ictal" lateralized periodic discharges.
AB  - OBJECTIVE: Whether lateralized periodic discharges (LPDs) represent ictal or
      interictal phenomena, and even the circumstances in which they may represent one
      or the other, remains highly controversial. Lateralized periodic discharges are,
      however, widely accepted as being ictal when they are time-locked to clinically
      apparent symptoms. We sought to investigate the characteristics of "ictal"
      lateralized periodic discharges (ILPDs) defined by time-locked clinical symptoms
      in order to explore the utility of using this definition to dichotomize LPDs into
      "ictal" and "nonictal" categories. METHODS: Our archive of all continuous EEG
      (cEEG) reports of adult inpatients undergoing prolonged EEG monitoring for
      nonelective indications between 2007 and 2011 was searched to identify all
      reports describing LPDs. Lateralized periodic discharges were considered ILPDs
      when they were reported as being consistently time-locked to clinical symptoms;
      LPDs lacking a clear time-locked correlate were considered to be "nonictal"
      lateralized periodic discharges (NILPDs). Patient charts and available
      neuroimaging studies were also reviewed. Neurophysiologic localization of LPDs,
      imaging findings, presence of seizures, discharge outcomes, and other demographic
      factors were compared between patients with ILPDs and those with NILPDs. p-Values
      were adjusted for false discovery rate (FDR). RESULTS: One thousand four hundred
      fifty-two patients underwent cEEG monitoring at our institution between 2007 and
      2011. Lateralized periodic discharges were reported in 90 patients, 10 of whom
      met criteria for ILPDs. Nine of the patients with ILPDs demonstrated motor
      symptoms, and the remaining patient experienced stereotyped sensory symptoms.
      Ictal lateralized periodic discharges had significantly increased odds for
      involving central head regions (odds ratio [OR]=11; 95% confidence interval
      [CI]=2.16-62.6; p=0.018, FDR adjusted), with a trend towards higher proportion of
      lesions involving the primary sensorimotor cortex (p=0.09, FDR adjusted).
      CONCLUSIONS: When defined by the presence of a time-locked clinical correlate,
      ILPDs appear to be strongly associated with a central EEG localization. This is
      likely due to cortical irritability in central head regions having greater
      propensity to manifest with positive, clinically apparent, and time-locked
      symptoms. Thus, dichotomization of ILPDs and NILPDs on this basis principally
      reflects differences in underlying anatomical locations of the periodic
      discharges rather than providing a clinically salient categorization.

PMID- 24935086
TI  - Segmental hair analysis for differentiation of tilidine intake from external
      contamination using LC-ESI-MS/MS and MALDI-MS/MS imaging.
AB  - Segmental hair analysis has been used for monitoring changes of consumption habit
      of drugs. Contamination from the environment or sweat might cause interpretative
      problems. For this reason, hair analysis results were compared in hair samples
      taken 24 h and 30 days after a single tilidine dose. The 24-h hair samples
      already showed high concentrations of tilidine and nortilidine. Analysis of wash
      water from sample preparation confirmed external contamination by sweat as
      reason. The 30-day hair samples were still positive for tilidine in all segments.
      Negative wash-water analysis proved incorporation from sweat into the hair
      matrix. Interpretation of a forensic case was requested where two children had
      been administered tilidine by their nanny and tilidine/nortilidine had been
      detected in all hair segments, possibly indicating multiple applications. Taking
      into consideration the results of the present study and of MALDI-MS imaging, a
      single application as cause for analytical results could no longer be excluded.
      Interpretation of consumption behaviour of tilidine based on segmental hair
      analysis has to be done with caution, even after typical wash procedures during
      sample preparation. External sweat contamination followed by incorporation into
      the hair matrix can mimic chronic intake. For assessment of external
      contamination, hair samples should not only be collected several weeks but also
      one to a few days after intake. MALDI-MS imaging of single hair can be a
      complementary tool for interpretation. Limitations for interpretation of
      segmental hair analysis shown here might also be applicable to drugs with
      comparable physicochemical and pharmacokinetic properties.

PMID- 24935087
TI  - Genotype-guided vs clinical dosing of warfarin and its analogues: meta-analysis
      of randomized clinical trials.
AB  - IMPORTANCE: Significant variations in dose requirements of warfarin and its
      analogues (acenocoumarol and phenprocoumon) make selecting the appropriate dose
      for an individual patient difficult. Genetic factors account for approximately
      one-third of the variation in dose requirement. The clinical usefulness of
      genotype-guided dosing of warfarin has been previously assessed in randomized
      clinical trials that were limited by lack of power and inconsistent results.
      OBJECTIVE: To compare genotype-guided initial dosing of warfarin and its
      analogues with clinical dosing protocols. DATA SOURCES AND STUDY SELECTION:
      MEDLINE (inception to December 31, 2013), EMBASE (inception to December 31,
      2013), and the Cochrane Library Central Register of Controlled Trials (inception
      to December 31, 2013) were searched for randomized clinical trials comparing
      genotype-guided warfarin dosing vs clinical dosing for adults with indications
      for anticoagulation. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted
      data independently on trial design, baseline characteristics, and outcomes. High
      quality studies were considered those that described an appropriate method of
      randomization, allocation concealment, blinding, and completeness of follow-up.
      MAIN OUTCOMES AND MEASURES: The outcomes analyzed included the percentage of time
      that the international normalized ratio (INR) was within the therapeutic range,
      the percentage of patients with an INR greater than 4, and the incidence of major
      bleeding and thromboembolic events. Summary standardized differences in means (or
      Mantel-Haenszel risk ratios) were obtained using a random-effects model. RESULTS:
      In 9 trials, 2812 patients were randomized to receive warfarin, acenocoumarol, or
      phenprocoumon according to a genotype-guided algorithm or a clinical dosing
      algorithm. Follow-up ranged from 4 weeks to 6 months (median, 12 weeks). The
      standardized difference in means of the percentage of time that the INR was
      within the therapeutic range was 0.14 (95% CI, -0.10 to 0.39) in the genotype
      guided dosing cohort (P = .25). The risk ratio for an INR greater than 4 was 0.92
      (95% CI, 0.82 to 1.05) for genotype-guided dosing vs clinical dosing. The risk
      ratios for major bleeding and thromboembolic events were 0.60 (95% CI, 0.29 to
      1.22) and 0.97 (95% CI, 0.46 to 2.05), respectively, for genotype-guided vs
      clinical dosing. CONCLUSIONS AND RELEVANCE: In this meta-analysis of randomized
      clinical trials, a genotype-guided dosing strategy did not result in a greater
      percentage of time that the INR was within the therapeutic range, fewer patients
      with an INR greater than 4, or a reduction in major bleeding or thromboembolic
      events compared with clinical dosing algorithms.

PMID- 24935088
TI  - Usefulness of contrast-enhanced 3-dimensional T1-VISTA in the diagnosis of facial
      neuritis: comparison with contrast-enhanced T1-TSE.
AB  - BACKGROUND AND PURPOSE: Compared with 2-dimensional imaging, 3D-reformatted
      imaging is a valuable technique that offers improved anatomic accuracy with
      minimal flow artifact and thinner sections without gaps between slices. Our aim
      was to evaluate the usefulness of CE 3D T1-VISTA with fat suppression sequences
      compared with CE T1-TSE with fat suppression sequences in patients with facial
      neuritis. MATERIAL AND METHODS: The study enrolled 32 consecutive patients who
      underwent IAC MR imaging for Bell's palsy. IAC MR scanning, including CE T1-VISTA
      and CE T1-TSE, was performed in all patients using a 3T scanner. The order of the
      scans was random. Signal intensity was measured at three segments (canalicular,
      labyrinthine, and anterior genu) of the facial nerve by drawing a ROI along the
      affected side and the normal side in each segment. We compared the quantitative
      CR of the two MR sequences with paired t-tests. RESULTS: In all three segments,
      the lesion-to-normal contrast ratios on CE 3D T1-VISTA (canalicular: 2.32;
      labyrinthine: 2.22; anterior genu: 1.97) were greater than those on CE T1-TSE
      (canalicular: 2.17; labyrinthine: 1.72; anterior genu: 1.68). The labyrinthine
      and anterior genu segments had significantly higher lesion-to-normal contrast
      ratios on CE 3D T1-VISTA in patients with facial neuritis (labyrinthine: P<0.001;
      anterior genu: P=0.002). CONCLUSION: CE 3D T1-VISTA was superior to CE T1-TSE in
      terms of image contrast between lesions and the normal facial nerve.

PMID- 24935089
TI  - Multiparametric 3T MRI in the evaluation of intraglandular prostate cancer:
      correlation with histopathology.
AB  - INTRODUCTION: Prostate cancer is common and may be treated immediately or managed
      conservatively by observation. We sought to determine how reliable
      multiparametric MRI is in the detection of intraprostatic prostate cancer and
      what role it has in risk stratification. METHODS: The histology from 38 whole
      mount prostate specimens was compared with preoperative multiparametric 3T MRI
      studies with an endorectal receiver coil in place. T1-weighted, T2-weighted,
      diffusion (b values 50 400 800), perfusion (Ve , Kep , Ktrans , area under the
      curve) and proton spectroscopic sequences were used. RESULTS: For cancers greater
      than 0.5 cc, the detection rate for combined T2-weighted imaging and diffusion
      weighted imaging (DWI) was 85%. For cancers 0.1 cc-0.5 cc, the sensitivity was
      52%.Per patient, false positive rate was 50% for combined T2-weighted imaging and
      DWI. Perfusion imaging had a sensitivity of 70% for tumours greater than 0.5 cc
      but had a per patient false positive rate of 80% influenced by benign prostatic
      hypertrophy. In only 15 patients could a satisfactory spectroscopy study be
      obtained. Weak correlation was found between the Gleason score and tumour size (r
      = 0.51), apparent diffusion coefficient (ADC) (r = -0.30) and (choline +
      creatine)/citrate ratio (r = 0.41). CONCLUSION: T2-weighted imaging and DWI in
      combination were the best strategy for detecting prostate cancer and had a
      sensitivity of 85% for detecting lesions greater than 0.5 cc. At 3T, an ADC
      threshold of between 1100-1200.10(-6)  mm(2) /s was optimal for diagnosing
      prostate cancer. There are significant limitations in the use of perfusion and
      spectroscopy to detect prostate cancer. Magnetic resonance imaging-targeted or
      guided biopsy post-MRI imaging is likely to be needed in some patients to assist
      risk stratification.

PMID- 24935090
TI  - Auranofin and related heterometallic gold(I)-thiolates as potent inhibitors of
      methicillin-resistant Staphylococcus aureus bacterial strains.
AB  - A series of new heterometallic gold(I) thiolates containing ferrocenyl-phoshines
      were synthesized. Their antimicrobial properties were studied and compared to
      that of FDA-approved drug, auranofin (Ridaura), prescribed for the treatment of
      rheumatoid arthritis. MIC in the order of one digit micromolar were found for
      most of the compounds against Gram-positive bacteria Staphylococcus aureus and CA
      MRSA strains US300 and US400. Remarkably, auranofin inhibited S. aureus, US300
      and US400 in the order of 150-300 nM. This is the first time that the potent
      inhibitory effect of auranofin on MRSA strains has been described. The effects of
      a selected heterometallic compound and auranofin were also studied in a non
      tumorigenic human embryonic kidney cell line (HEK-293).

PMID- 24935091
TI  - Mono and dinuclear phosphinegold(I) sulfanylcarboxylates: influence of nuclearity
      and substitution of PPh3 for PEt3 on cytotoxicity.
AB  - Gold complexes of the type [Au(PEt3)(Hxspa)] were prepared by reacting
      triethylphosphinegold(I) chloride in ethanol/water (8:1) with the 3-(aryl)-2
      sulfanylpropenoic acids H2xspa [x=p=3-phenyl-; f=3-(2-furyl)-; t=3-(2-thienyl)-;
      py=3-(2-pyridyl); Clp=3-(2-Chlorophenyl)-; -o-mp=3-(2-methoxyphenyl)-; -p-mp=3-(4
      methoxyphenyl)-; -o-hp=3-(2-hydroxyphenyl)-; -p-hp=3-(4-hydroxyphenyl)-; -diBr-o
      hp=3-(3,5-dibromo-2-hidroxyphenyl-); spa=2-sulfanylpropenoato] or 2
      cyclopentylidene-2-sulfanylacetic acid (H2cpa) and KOH in a 1:1:1 mole ratio. The
      compounds were characterized by IR spectroscopy and FAB mass spectrometry and by
      (1)H, (13)C and (31)P NMR spectroscopy. The in vitro antitumor activity of these
      and of the previously described dinuclear [(AuPEt3)2(xspa)] complexes against the
      HeLa-229, A2780 and A2780cis cell lines was determined and compared with those of
      the analogous PPh3 complexes. The results show that the substitution of the PPh3
      ligand by PEt3 is particularly effective in increasing the cytotoxicity of the
      dinuclear [(AuPR3)2(xspa)] complexes, giving rise to compounds that are
      significantly more active than cisplatin against the aforementioned cell lines.
      In addition, and as a preliminary test for nephrotoxicity, the cytotoxicity of
      the most active compounds against the normal renal LCC-PK1 cell line was
      evaluated and compared with that of cisplatin. 

PMID- 24935092
TI  - Copper(II) complexes of alloferon 1 with point mutations (H1A) and (H9A)
      stability structure and biological activity.
AB  - Mono- and polynuclear copper(II) complexes of the alloferon 1 with point
      mutations (H1A) A(1)GVSGH(6)GQH(9)GVH(12)G (Allo1A) and (H9A)
      H(1)GVSGH(6)GQA(9)GVH(12)G (Allo9A) have been studied by potentiometric, UV
      visible, CD, EPR spectroscopic and mass spectrometry (MS) methods. To obtain a
      complete complex speciation different metal-to-ligand molar ratios ranging from
      1:1 to 4:1 for Allo1A and to 3:1 for Allo9A were studied. The presence of the His
      residue in first position of the peptide chain changes the coordination abilities
      of the Allo9A peptide in comparison to that of the Allo1A. Imidazole-N3 atom of N
      terminal His residue of the Allo9A peptide forms stable 6-membered chelate with
      the terminal amino group. Furthermore, the presence of two additional histidine
      residues in the Allo9A peptide (H(6),H(12)) leads to the formation of the CuL
      complex with 4N {NH2,NIm-H(1),NIm-H(6),NIm-H(12)} binding site in wide pH range
      (5-8). For the Cu(II)-Allo1A system, the results demonstrated that at
      physiological pH7.4 the predominant complex the CuH-1L consists of the 3N {NH2,N(
      ),CO,NIm} coordination mode. The inductions of phenoloxidase activity and
      apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II)
      complexes at pH7.4 were studied. The Allo1A, Allo1K peptides and their copper(II)
      complexes displayed the lowest hemocytotoxic activity while the most active was
      the Cu(II)-Allo9A complex formed at pH7.4. The results may suggest that the N
      terminal-His(1) and His(6) residues may be more important for their proapoptotic
      properties in insects than those at positions 9 and 12 in the peptide chain. 

PMID- 24935093
TI  - Silver carboxylate metal-organic frameworks with highly antibacterial activity
      and biocompatibility.
AB  - Two novel Ag-based metal-organic frameworks (MOFs) [Ag2(O-IPA)(H2O).(H3O)] (1)
      and [Ag5(PYDC)2(OH)] (2) were synthesized under the hydrothermal conditions using
      aromatic-carboxylic acids containing hydroxyl and pyridyl groups as ligands (HO
      H2IPA=5-hydroxyisophthalic acid and H2PYDC=pyridine-3, 5-dicarboxylic acid).
      Single crystal X-ray diffraction indicated that two compounds exhibit three
      dimensional frameworks constructed from different rod-shaped molecular building
      blocks. Both compounds favor slow release of Ag(+) ions leading to excellent and
      long-term antimicrobial activities towards Gram-negative bacteria, Escherichia
      coli (E. coli) and Gram-positive bacteria, Staphylococcus aureus (S. aureus).
      Their antibacterial potency was evaluated by using a minimal inhibition
      concentration (MIC) benchmark and an inhibition zone testing. High-resolution
      transmission electron microscope images indicate that the Ag-based MOFs could
      rupture the bacterial membrane resulting in cell death. Hematological study
      showed that these MOFs exhibit good biocompatibility in mice. In addition, good
      thermal stability and optical stability under UV-visible and visible light are
      beneficial for their antibacterial application. 

PMID- 24935094
TI  - American Medical Association calls for stricter regulation of electronic
      cigarettes.

PMID- 24935096
TI  - The practice of 'doing' evaluation: lessons learned from nine complex
      intervention trials in action.
AB  - BACKGROUND: There is increasing recognition among trialists of the challenges in
      understanding how particular 'real-life' contexts influence the delivery and
      receipt of complex health interventions. Evaluations of interventions to change
      health worker and/or patient behaviours in health service settings exemplify
      these challenges. When interpreting evaluation data, deviation from intended
      intervention implementation is accounted for through process evaluations of
      fidelity, reach, and intensity. However, no such systematic approach has been
      proposed to account for the way evaluation activities may deviate in practice
      from assumptions made when data are interpreted. METHODS: A collective case study
      was conducted to explore experiences of undertaking evaluation activities in the
      real-life contexts of nine complex intervention trials seeking to improve
      appropriate diagnosis and treatment of malaria in varied health service settings.
      Multiple sources of data were used, including in-depth interviews with
      investigators, participant-observation of studies, and rounds of discussion and
      reflection. RESULTS AND DISCUSSION: From our experiences of the realities of
      conducting these evaluations, we identified six key 'lessons learned' about ways
      to become aware of and manage aspects of the fabric of trials involving the
      interface of researchers, fieldworkers, participants and data collection tools
      that may affect the intended production of data and interpretation of findings.
      These lessons included: foster a shared understanding across the study team of
      how individual practices contribute to the study goals; promote and facilitate
      within-team communications for ongoing reflection on the progress of the
      evaluation; establish processes for ongoing collaboration and dialogue between
      sub-study teams; the importance of a field research coordinator bridging everyday
      project management with scientific oversight; collect and review reflective field
      notes on the progress of the evaluation to aid interpretation of outcomes; and
      these approaches should help the identification of and reflection on possible
      overlaps between the evaluation and intervention. CONCLUSION: The lessons we have
      drawn point to the principle of reflexivity that, we argue, needs to become part
      of standard practice in the conduct of evaluations of complex interventions to
      promote more meaningful interpretations of the effects of an intervention and to
      better inform future implementation and decision-making.

PMID- 24935095
TI  - Distinct functions of the laminin beta LN domain and collagen IV during cardiac
      extracellular matrix formation and stabilization of alary muscle attachments
      revealed by EMS mutagenesis in Drosophila.
AB  - BACKGROUND: The Drosophila heart (dorsal vessel) is a relatively simple tubular
      organ that serves as a model for several aspects of cardiogenesis. Cardiac
      morphogenesis, proper heart function and stability require structural components
      whose identity and ways of assembly are only partially understood. Structural
      components are also needed to connect the myocardial tube with neighboring cells
      such as pericardial cells and specialized muscle fibers, the so-called alary
      muscles. RESULTS: Using an EMS mutagenesis screen for cardiac and muscular
      abnormalities in Drosophila embryos we obtained multiple mutants for two
      genetically interacting complementation groups that showed similar alary muscle
      and pericardial cell detachment phenotypes. The molecular lesions underlying
      these defects were identified as domain-specific point mutations in LamininB1 and
      Cg25C, encoding the extracellular matrix (ECM) components laminin beta and
      collagen IV alpha1, respectively. Of particular interest within the LamininB1
      group are certain hypomorphic mutants that feature prominent defects in cardiac
      morphogenesis and cardiac ECM layer formation, but in contrast to amorphic
      mutants, only mild defects in other tissues. All of these alleles carry clustered
      missense mutations in the laminin LN domain. The identified Cg25C mutants display
      weaker and largely temperature-sensitive phenotypes that result from glycine
      substitutions in different Gly-X-Y repeats of the triple helix-forming domain.
      While initial basement membrane assembly is not abolished in Cg25C mutants,
      incorporation of perlecan is impaired and intracellular accumulation of perlecan
      as well as the collagen IV alpha2 chain is detected during late embryogenesis.
      CONCLUSIONS: Assembly of the cardiac ECM depends primarily on laminin, whereas
      collagen IV is needed for stabilization. Our data underscore the importance of a
      correctly assembled ECM particularly for the development of cardiac tissues and
      their lateral connections. The mutational analysis suggests that the
      beta6/beta3/beta8 interface of the laminin beta LN domain is highly critical for
      formation of contiguous cardiac ECM layers. Certain mutations in the collagen IV
      triple helix-forming domain may exert a semi-dominant effect leading to an
      overall weakening of ECM structures as well as intracellular accumulation of
      collagen and other molecules, thus paralleling observations made in other
      organisms and in connection with collagen-related diseases.

PMID- 24935097
TI  - Effects of prior oral exposure to combinations of environmental immunosuppressive
      agents on ovalbumin allergen-induced allergic airway inflammation in Balb/c mice.
AB  - Abstract Humans are exposed daily to multiple environmental chemicals in the
      atmosphere, in food, and in commercial products. Therefore, hazard identification
      and risk management must account for exposure to chemical mixtures. The objective
      of the study reported here was to investigate the effects of combinations of
      three well-known environmental immunotoxic chemicals - methoxychlor (MXC), an
      organochlorine compound; parathion (PARA), an organophosphate compound; and
      piperonyl butoxide (PBO), an agricultural insecticide synergist - by using a
      mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Four-week
      old Balb/c mice were exposed orally to either one or two of the environmental
      immunotoxic chemicals for five consecutive days, prior to intraperitoneal
      sensitization with OVA and an inhalation challenge. We assessed IgE levels in
      serum, B-cell counts, and cytokine production in hilar lymph nodes, and
      differential cell counts and levels of related chemokines in bronchoalveolar
      lavage fluid (BALF). Mice treated with MXC + PARA or PBO + MXC showed marked
      increases in serum IgE, IgE-positive B-cells and cytokines in lymph nodes, and
      differential cell counts and related chemokines in BALF compared with mice that
      received the vehicle control or the corresponding individual test substances.
      These results suggest that simultaneous exposure to multiple environmental
      chemicals aggravates allergic airway inflammation more than exposure to
      individual chemicals. It is expected that the results of this study will help
      others in their evaluation of immunotoxic combinational effects when conducting
      assessments of the safety of environmental/occupational chemicals. 

PMID- 24935098
TI  - Current evidence of transurethral Ho:YAG and Tm:YAG treatment of bladder cancer:
      update 2014.
AB  - INTRODUCTION: Bladder cancer (BC) represents a growing health care problem
      worldwide. In times of tight budgets and an aging society, new strategies for the
      transurethral treatment of BC are needed. Laser devices used for tumor
      vaporization and/or en bloc resection provide an alternative to parvenu
      strategies. MATERIALS AND METHODS: Medline/Cochrane search was performed using
      following terms: bladder cancer, urothelial carcinoma, laser, en bloc,
      vaporization, photoablation, holmium, thulium, Ho:YAG, Tm:YAG, HoLRBT and TmLRBT.
      Last date of search was February 12, 2014. RESULTS: Eighteen publications in
      English were identified including 800 patients (Ho:YAG = 652 patients and Tm:YAG
      = 148 patients). Data on en bloc resection techniques were presented in 10
      publications, 7 publications provided data of tumor vaporization and one
      publication presented data on both. Level of evidence based on SIGN is mainly 3
      (non-analytic studies); only three studies are level 2 (prospective case control
      studies). Tumor vaporization seems to be a promising alternative for the
      treatment of recurrent tumors in selected patients. It can be performed in an
      office-based approach without the need of general anesthesia. The use of
      photodynamic diagnostic might enhance surgical quality. The principle of en bloc
      resection should provide accurate staging in most cases; however, data on this
      important aspect are missing. Peri- and postoperative complications are scarce.
      Due to the nature of the energy source, bladder perforation caused by obturator
      nerve reflex is highly unlikely when using lasers. There is a trend toward
      decreased infield recurrence rates. CONCLUSIONS: Lasers are potentially useful
      alternatives to conventional TURBT, but systematical assessments using
      standardized classification systems and well-designed RCTs are needed to make
      results comparable.

PMID- 24935099
TI  - Effects of mutual shading on the regulation of photosynthesis in field-grown
      sorghum.
AB  - In the field, close planting inevitably causes mutual shading and depression of
      leaf photosynthesis. To clarify the regulative mechanisms of photosynthesis under
      these conditions, the effects of planting density on leaf structure, gas exchange
      and proteomics were carefully studied in field-grown sorghum. In the absence of
      mineral deficiency, (1) close planting induced a significant decrease in light
      intensity within populations, which further resulted in much lower stomatal
      density and other anatomical characteristics associated with shaded leaves; (2)
      sorghum grown at high planting density had a lower net photosynthetic rate and
      stomatal conductance than those grown at low planting density; (3) approximately
      62 protein spots changed their expression levels under the high planting density
      conditions, and 22 proteins associated with photosynthesis were identified by
      mass spectrometry. Further analysis revealed the depression of photosynthesis
      caused by mutual shading involves the regulation of leaf structure, absorption
      and transportation of CO2, photosynthetic electron transport, production of
      assimilatory power, and levels of enzymes related to the Calvin cycle.
      Additionally, heat shock protein and oxygen-evolving enhancer protein play
      important roles in photoprotection in field-grown sorghum. A model for the
      regulation of photosynthesis under mutual shading was suggested based on our
      results. 

PMID- 24935100
TI  - Understanding delayed access to antenatal care: a qualitative interview study.
AB  - BACKGROUND: Delayed access to antenatal care ('late booking') has been linked to
      increased maternal and fetal mortality and morbidity. The aim of this qualitative
      study was to understand why some women are late to access antenatal care.
      METHODS: 27 women presenting after 19 completed weeks gestation for their first
      hospital booking appointment were interviewed, using a semi-structured format, in
      community and maternity hospital settings in South Yorkshire, United Kingdom.
      Interviews were transcribed verbatim and entered onto NVivo 8 software. An
      interdisciplinary, iterative, thematic analysis was undertaken. RESULTS: The late
      booking women were diverse in terms of: age (15-37 years); parity (0-4);
      socioeconomic status; educational attainment and ethnicity. Three key themes
      relating to late booking were identified from our data: 1) 'not knowing':
      realisation (absence of classic symptoms, misinterpretation); belief (age,
      subfertility, using contraception, lay hindrance); 2) 'knowing': avoidance
      (ambivalence, fear, self-care); postponement (fear, location, not valuing care,
      self-care); and 3) 'delayed' (professional and system failures,
      knowledge/empowerment issues). CONCLUSIONS: Whilst vulnerable groups are strongly
      represented in this study, women do not always fit a socio-cultural stereotype of
      a 'late booker'. We report a new taxonomy of more complex reasons for late
      antenatal booking than the prevalent concepts of denial, concealment and
      disadvantage. Explanatory sub-themes are also discussed, which relate to
      psychological, empowerment and socio-cultural factors. These include poor
      reproductive health knowledge and delayed recognition of pregnancy, the influence
      of a pregnancy 'mindset' and previous pregnancy experience, and the perceived
      value of antenatal care. The study also highlights deficiencies in early
      pregnancy diagnosis and service organisation. These issues should be considered
      by practitioners and service commissioners in order to promote timely antenatal
      care for all women.

PMID- 24935102
TI  - Theoretical predictions of isotope effects versus their experimental values for
      an example of uncatalyzed hydrolysis of atrazine.
AB  - Kinetic isotope effects are one of the most powerful experimental techniques for
      establishing the nature of a chemical process. However their interpretation very
      often seeks support from electronic structure calculations in order to get
      detailed information regarding the transition state which is not experimentally
      available. For an example of atrazine hydrolysis we have shown how the match
      between experimentally and theoretically determined magnitudes of carbon,
      nitrogen and chlorine kinetic isotope effects can be used to discuss the
      mechanism under different reaction conditions. Two different density functionals
      combined with the explicit presence of solvent molecules and a continuum
      solvation model revealed that although the reaction proceeds via the same
      concerted mechanism regardless of the reaction conditions the transition state
      structure for an acid and base-catalyzed pathway is different. 

PMID- 24935101
TI  - Antiproliferative activity and induction of apoptotic by ethanolic extract of
      Alpinia galanga rhizhome in human breast carcinoma cell line.
AB  - BACKGROUND: We investigated the potential of galangal rhizomes to induce
      cytotoxic and apoptotic effects in the cultured human breast carcinoma cell line,
      (MCF-7) in compare with the non-malignant (MRC-5) cells. METHODS: Both cells were
      cultured in DMEM medium and treated with galangal rhizomes for three consecutive
      days. The percentage of apoptotic cells was determined by flow cytometry using
      Annexin-V fluorescein isothiocyanate. RESULTS: The results showed that the
      ethanolic extract of galangal rhizomes decreased cell viability in the malignant
      cells as a concentration- and time- dependent manner. The IC50 values against MCF
      7 were determined at 400.0 +/- 11.7 and 170.0 +/- 5.9 MUg/ml after 48 and 72 h
      respectively. The morphology of MCF-7 cells treated with the ethanolic extract
      confirmed the cell proliferation assay results. Alpinia galanga induced apoptosis
      in MCF-7 cells, as determined by flow cytometry. CONCLUSIONS: We concluded that
      the extract of Alpinia galanga exerts pro-apoptotic effects in a breast cancer
      derived cell line and could be considered as a potential chemotherapeutic agent
      in breast cancer.

PMID- 24935103
TI  - An innovative synergistic grid approach to the computational study of protein
      aggregation mechanisms.
AB  - Thanks to the advances in grid technologies, we are able to propose here an
      evolution of our molecular simulator that, when moving to larger systems, instead
      of reducing the granularity of the dynamical treatment (as is often done in
      molecular dynamics studies of such systems) exploits the extra power of the grid
      approach to the end of preserving the detailed nature of theatomistic formulation
      of the interaction. Key steps of such evolution are: (1) the assemblage of the
      interaction based on a composition of the ab initio intramolecular data and a
      portable parameterization of the intermolecular potential linking ab initio
      evaluation of intramolecular potentials and the partitioning of molecular
      polarizability; (2) the exploitation of an efficient coordinated porting and
      running of molecular dynamics codes on the European grid distributed computing
      infrastructure. As a prototype case study, the N-methylacetamide dimer in vacuo
      has been considered and the formation of possible conformers is analyzed. 

PMID- 24935104
TI  - Understanding electrostatic and steric requirements related to hypertensive
      action of AT(1) antagonists using molecular modeling techniques.
AB  - AT1 receptor is an interesting biological target involved in several important
      diseases, such as blood hypertension and cardiovascular pathologies. In this
      study we investigated the main electrostatic and steric features of a series of
      AT1 antagonists related to hypertensive activity using structure and ligand-based
      strategies (docking and CoMFA). The generated 3D model had good internal and
      external consistency and was used to predict the potency of an external test set.
      The predicted values of pIC50 are in good agreement with the experimental results
      of biological activity, indicating that the 3D model can be used to predict the
      biological property of untested compounds. The electrostatic and steric CoMFA
      maps showed molecular recognition patterns, which were analyzed with structure
      based molecular modeling studies (docking). The most and the least potent
      compounds docked into the AT1 binding site were subjected to molecular dynamics
      simulations with the aim to verify the stability and the flexibility of the
      ligand-receptor interactions. These results provided valuable insights on the
      electronic/structural requirements to design novel AT1 antagonists. 

PMID- 24935105
TI  - A rational reduction of CI expansions: combining localized molecular orbitals and
      selected charge excitations.
AB  - Based on localized molecular orbitals, the proposed method reduces large
      configuration interaction (CI) spaces while maintaining agreement with reference
      values. Our strategy concentrates the numerical effort on physically pertinent CI
      contributions and is to be considered as a tool to tackle large systems including
      numerous open-shells. To show the efficiency of our method we consider two 4
      electron parent systems. First, we illustrate our approach by describing the van
      der Waals interactions in the (H2)2 system. By systematically including local
      correlation, dispersion and charge transfer mechanisms, we show that 90% of the
      reference full CI dissociation energy of the H2 dimer is reproduced using only 3%
      of the full CI space. Second, the conformational cis/trans rotation barrier of
      the butadiene molecule is remarkably reproduced (97% of the reference value) with
      less than 1% of the reference space. This work paves the way to numerical
      strategies which afford the electronic structure determination of large open
      shell systems avoiding the exponential limitation. At the same time, a physical
      analysis of the contents of the wave function is offered.

PMID- 24935106
TI  - A comparison of various optimization algorithms of protein-ligand docking
      programs by fitness accuracy.
AB  - In protein-ligand docking, an optimization algorithm is used to find the best
      binding pose of a ligand against a protein target. This algorithm plays a vital
      role in determining the docking accuracy. To evaluate the relative performance of
      different optimization algorithms and provide guidance for real applications, we
      performed a comparative study on six efficient optimization algorithms,
      containing two evolutionary algorithm (EA)-based optimizers (LGA, DockDE) and
      four particle swarm optimization (PSO)-based optimizers (SODock, varCPSO, varCPSO
      ls, FIPSDock), which were implemented into the protein-ligand docking program
      AutoDock. We unified the objective functions by applying the same scoring
      function, and built a new fitness accuracy as the evaluation criterion that
      incorporates optimization accuracy, robustness, and efficiency. The varCPSO and
      varCPSO-ls algorithms show high efficiency with fast convergence speed. However,
      their accuracy is not optimal, as they cannot reach very low energies. SODock has
      the highest accuracy and robustness. In addition, SODock shows good performance
      in efficiency when optimizing drug-like ligands with less than ten rotatable
      bonds. FIPSDock shows excellent robustness and is close to SODock in accuracy and
      efficiency. In general, the four PSO-based algorithms show superior performance
      than the two EA-based algorithms, especially for highly flexible ligands. Our
      method can be regarded as a reference for the validation of new optimization
      algorithms in protein-ligand docking. 

PMID- 24935107
TI  - Substituent effects on molecular properties of dicarba-closo-dodecarborane
      derivatives.
AB  - In this paper we study the role played by substituent effects on reactivity and
      NLO properties of ortho-, meta- and para- dicarba-closo-dodecarborane derivatives
      at B3LYP/6-31G(d,p) level of theory. In addition correlations with Hammett
      parameters of the substituents were established. In accordance with obtained
      results the reactivity properties of derivatives have not been significantly
      influenced by the isomer type, however the replaced para isomers were the most
      sensitive to NLO calculations. Moreover, the push-pull para isomers were found to
      be the most reactive and displayed the largest values of beta tot and dipole
      moment.

PMID- 24935108
TI  - Apparent basicities of the surfaces characterizing the dominant crystal habits of
      distinct polymorphic forms of 4-aminosulfonamide.
AB  - A new approach for estimating local basicities/acidities of groups exposed on
      crystal surfaces was formulated and validated. The model, constructed within a
      quantitative structure-property relationship (QSPR) framework, allowed the
      expression of the protonic properties of amine and sulfonamide groups as
      functions of simple molecular descriptors of geometric types. This enabled the
      application of a QM/MM approach for the structural optimization of SNM molecules
      located on the surfaces of the dominant crystal habits. The obtained pKa values
      were used for classification of the protonic properties of four p
      aminosulfonamide (SNM) polymorphs. The computed distributions of the surface pK a
      values suggested that, for all polymorphs, the amino group has statistically the
      same proton-accepting ability on the crystal surface as in bulk water solution.
      Although sulfonamide groups on the crystal surface-especially those distributed
      on beta- and gamma-dominant faces-seem to be more acidic compared to bulk water
      solution, the pK a values are statistically indistinguishable irrespective of the
      morphology. This suggests that experimentally observed differences in the
      perichromic properties of SNM polymorphs do not arise from local pH changes,
      Thus, apparent local basicities are to be relaed to structural similarity of SNM
      surfaces and thymol blue conformers anabling direct interactions. 

PMID- 24935109
TI  - Theoretical study on the reaction mechanism of carbaryl with OH radicals.
AB  - A theoretical investigation on the multiple-channel degradation mechanism of
      carbaryl with .OH in the atmosphere was completed by the variational transition
      state theory. Eleven reaction channels have been identified using the density
      functional theory. The equilibrium geometries and the corresponding harmonic
      vibrational frequencies of the stationary points were obtained at the B3LYP/6
      31++G(d,p) level. The minimum energy paths were calculated at the same level, and
      energetic information was further refined at the B3LYP/6-31++G(3df,2p) level. The
      rate constants of the 11 reaction channels were calculated by improved canonical
      variational transition state theory with small-curvature tunneling correction
      over the temperature range 200-800 K. The total rate constants are in good
      agreement with available experimental data and the three-parameter expression
      k(T) = 1.85 * 10(-21)  T (3.44)exp(1180.18/T) cm(3) molecule(-1) s(-1) was given.

PMID- 24935110
TI  - DFT study of sulfur derivatives of cumulenes and their protonated forms of
      interstellar interest and calculations of dissociation energies of protonated
      forms (SC(CH)C(n-2)S)(+) (n = 3-8).
AB  - A theoretical study of the sulfur cumulenes SCnS (n = 3-8), CnS ( n = 1-8) and of
      their protonated forms (SCnS)H(+) and (CnS)H(+) that might exist in the
      interstellar environment, has been carried out by means of the standard B3LYP/6
      311G** method. The geometries and relative energies of singlet and triplet states
      according to the number of carbons have been computed. Like neutral species, we
      have found that the ground state of the most stable protonated forms (SC(CH)Cn
      2S)(+) and ((HC)Cn-1S)(+), alternates between a triplet state for the even series
      and a singlet state for the odd series. We provided the data needed to simulate
      infrared and microwave spectra (vibration frequencies, dipole moments, and
      rotational constants) for each protonated species (SCnS)H(+) and (CnS)H(+) and
      for each neutral CnS species. The computing of dissociation energies of the most
      stable protonated forms (SC(CH)Cn-2S)(+) (n = 3-8) has shown that the lowest
      values are obtained for the dissociation of compounds with an even number of
      carbons, in their triplet state, which produce the observed fragments CS and C3S.
      The dissociation of even protonated forms requires less energy than for the odd
      protonated forms.

PMID- 24935112
TI  - Potential energy function information from quantum phase shift using the variable
      phase method.
AB  - The present work discusses quantum phase shift sensitivity analysis with respect
      to the potential energy function. A set of differential equations for the
      functional derivative of the quantum phase shift with respect to the potential
      energy function was established and coupled with the variable phase equation.
      This set of differential equations provides a simple, exact and straightforward
      way to establish the sensitivity matrix. The present procedure is easier to use
      than the finite difference approach, in which several direct problems have to be
      addressed. Furthermore, integration of the established equations can be used to
      demonstrate how the sensitivity phase shift is accumulated as a function of the
      interatomic distance. The potential energy function was refined to produce a
      better quality function. The average error on the phase shift decreased from 9.8%
      in the original potential function to 0.13% in the recovered potential. The
      present procedure is an important initial step for further work towards
      recovering potential energy functions in upper dimensions or to recovering this
      function from cross sections.

PMID- 24935111
TI  - Evaluation of active designs of cephalosporin C acylase by molecular dynamics
      simulation and molecular docking.
AB  - Optimization to identify the global minimum energy conformation sequence in in
      silico enzyme design is computationally non-deterministic polynomial-time (NP)
      hard, with the search time growing exponentially as the number of design sites
      increases. This drawback forces the modeling of protein-ligand systems to adopt
      discrete amino acid rotamers and ligand conformers, as well as continuum solvent
      treatment of the environment; however, such compromises produce large numbers of
      false positives in sequence selection. In this report, cephalosporin acylase,
      which catalyzes the hydrolytic reaction of cephalosporin C to 7
      aminocephalosporanic acid, was used to investigate the dynamic features of active
      site-transition-state complex structures using molecular dynamics (MD)
      simulations to potentially eliminate false positives. The molecular docking
      between cephalosporin C and wild type acylase N176 and its eight mutants showed
      that the rate-limiting step in the hydrolytic reaction of cephalosporin C is the
      acylation process. MD simulations of the active-site-transition-state complex
      structures of the acylation processes for N176 and its eight mutants showed that
      the geometrical constraints between catalytic residues and small molecule
      transition states are always well maintained during the 20 ns simulation for
      mutants with higher activities, and more hydrogen bonds between binding residues
      and functional groups of the ligand side chain in the active pocket are formed
      for mutants with higher activities. The conformations of the ligand transition
      states were changed greatly after the simulation. This indicates that the
      hydrogen bond network between the ligand and protein could be improved to enhance
      the activity of cephalosporin C acylase in subsequent design. 

PMID- 24935113
TI  - Elucidating the structural basis of diphenyl ether derivatives as highly potent
      enoyl-ACP reductase inhibitors through molecular dynamics simulations and 3D-QSAR
      study.
AB  - Diphenyl ether derivatives are good candidates for anti-tuberculosis agents that
      display a promising potency for inhibition of InhA, an essential enoyl-acyl
      carrier protein (ACP) reductase involved in fatty acid biosynthesis pathways in
      Mycobacterium tuberculosis. In this work, key structural features for the
      inhibition were identified by 3D-QSAR CoMSIA models, constructed based on
      available experimental binding properties of diphenyl ether inhibitors, and a set
      of four representative compounds was subjected to MD simulations of inhibitor
      InhA complexes for the calculation of binding free energies. The results show
      that bulky groups are required for the R1 substituent on the phenyl A ring of the
      inhibitors to favor a hydrophobic pocket formed by residues Phe149, Met155,
      Pro156, Ala157, Tyr158, Pro193, Met199, Val203, Leu207, Ile215, and Leu218. Small
      substituents with a hydrophilic property are required at the R3 and R4 positions
      of the inhibitor phenyl B rings to form hydrogen bonds with the backbones of
      Gly96 and Met98, respectively. For the R2 substituent, small substituents with
      simultaneous hydrophilic or hydrophobic properties are required to favor the
      interaction with the pyrophosphate moiety of NAD(+) and the methyl side chain of
      Ala198, respectively. The reported data provide structural guidance for the
      design of new and potent diphenyl ether-based inhibitors with high inhibitory
      activities against M. tuberculosis InhA. 

PMID- 24935114
TI  - Medium-term outcome of recipients of marginal donor hearts selected with new
      stress-echocardiographic techniques over standard criteria.
AB  - BACKGROUND: Heart transplantation is limited by severe donor organ shortage.
      Regardless of the changes made in the acceptance of marginal donors, any such
      mechanism cannot be considered successful unless recipient graft survival rates
      remain acceptable. A stress echo-driven selection of donors has proven successful
      in older donors with normal left ventricular resting function and in standard
      donors with reversible resting left ventricular dysfunction acutely improving
      during stress, or slowly improving (over hours) during intensive hormonal
      treatment. Aim of this study is to assess the medium-term outcome of recipients
      of marginal donor hearts selected with new echocardiographic techniques over
      standard criteria. METHODS AND RESULTS: We enrolled 43 recipients of marginal
      donor hearts: age > 55 years, or < 55 years but with concomitant risk factors, n
      = 32; acutely improving during stress, n = 3; or slowly improving during hormonal
      treatment, n = 8. At follow-up (median, 30 months; interquartile range, 21-52
      months), 37 of the recipients were still alive. One-year survival was 93%.
      CONCLUSION: The strict use of new stress-echocardiographic techniques over
      standard criteria of marginal donor management, together with comprehensive
      monitoring of the donor, has the potential to substantially increase the number
      of donor hearts without adverse effects on recipient medium-term outcome.

PMID- 24935115
TI  - Pregnancy during breast cancer: does a mother's parity status modify an
      offspring's mortality risk?
AB  - To assess whether children born to primiparous women around the time of a breast
      cancer diagnosis have an increased mortality risk. From the merged Swedish Multi
      Generation and Cancer Registers, we identified 49,750 eligible children whose
      mother was diagnosed with breast cancer between 1958 and 2010. Mortality rates in
      offspring were compared to the background population using standardized mortality
      ratios (SMR), adjusted for calendar year of birth, attained age, and sex, and
      calculated for each category of timing of delivery (before, around, or after
      mother's diagnosis) and mother's parity status. Hazard ratios were assessed using
      a Cox proportional hazards model and adjusted for socioeconomic status, year of
      birth and mother's age at birth. Children born to a primiparous woman around a
      breast cancer diagnosis had a mortality rate five times greater than the
      background population (SMR 5.26, 95 % CI 1.93-11.5), whereas children born to a
      multiparous woman had a twofold increase (SMR 2.40, 95 % CI 1.10-4.55). Children
      of primiparous women born around diagnosis had an adjusted hazard ratio fourfold
      to that of children of primiparous women born before their mother's diagnosis (HR
      4.29, 95 % CI 1.68-8.91), whereas hazard ratios for children of primiparous or
      multiparous women born at other times were not statistically significant.
      Children born to primiparous women around a breast cancer diagnosis have an
      increased relative mortality risk. Although relative risk is increased, in
      absolute terms children born from a cancer complicated pregnancy do relatively
      well. Additional investigations are needed to elucidate the reason(s) underlying
      this observation before the information can be used to inform patient counseling
      and clinical care.

PMID- 24935116
TI  - Automated radiochemical synthesis and biodistribution of [11C]l-alpha
      acetylmethadol ([11C]LAAM).
AB  - Long-acting opioid agonists methadone and l-alpha-acetylmethadol (LAAM) prevent
      withdrawal in opioid-dependent persons. Attempts to synthesize [(11)C]-methadone
      for PET evaluation of brain disposition were unsuccessful. Owing, however, to
      structural and pharmacologic similarities, we aimed to develop [(11)C]LAAM as a
      PET ligand to probe the brain exposure of long-lasting opioids in humans. This
      manuscript describes [(11)C]LAAM synthesis and its biodistribution in mice. The
      radiochemical synthetic strategy afforded high radiochemical yield, purity and
      specific activity, thereby making the synthesis adaptable to automated modules. 

PMID- 24935117
TI  - Evaluation of silica/ferrocyanide composite as a dual-function material for
      simultaneous removal of 137Cs+ and 99TcO4- from aqueous solutions.
AB  - A novel mesoporous silica-coated ferrocyanide (MSCFC) composite was successfully
      synthesized and evaluated as a dual-function material for simultaneous removal of
      (137)Cs(+) cations and (99)TcO4(-) anions from aqueous solutions. Sorption
      behavior of both radionuclides on MSCFC under different experimental conditions
      has been studied using a batch technique. Results revealed that about 100% of
      (137)Cs(+) and 97% of (99)TcO4(-) were removed by MSCFC in the pH ranges of 2.2
      12.4 and 4.1-9.5, respectively. Sorption kinetic data were analyzed by pseudo
      first-order, pseudo-second-order and intraparticle diffusion kinetic models,
      while Langmuir and Freundlich models were applied for the sorption isotherms. The
      maximum sorption capacity of MSCFC for radiocesium was determined and compared
      with other reported sorbents. Applicability of the coated ferrocyanide for
      simultaneous removal of (137)Cs(+) and (99)TcO4(-) from low-level liquid
      radioactive waste (LLLW) was also tested, and the data revealed that 99.91% and
      98.34% were removed from (137)Cs(+) and (99)TcO4(-), respectively. It is
      concluded that MSCFC exhibits excellent efficiency for simultaneous removal of
      the mixed radionuclides with different charge from LLLW. 

PMID- 24935118
TI  - Spatial velocity distributions in pulse-wave propagation based on fluid-structure
      interaction.
AB  - In this paper, spatial velocity distributions in pulse-wave propagation based on
      a fluid-structure interaction model are presented. The investigation is performed
      using the assumption of laminar flow and a linear-elastic wall. The fluid
      structure interaction scheme is constructed using the finite element method. The
      results show that velocity distributions embody an obvious time delay in an
      elastic tube model. Further, the fully developed flow is delayed and the velocity
      values are increased in comparison with a rigid tube model. The increase in the
      wall thickness makes the time delay between the velocity peaks of different sites
      smaller while the time delay between the velocity minima is unchanged. Similarly,
      the time delay between the velocity bottoms is more easily found when decreasing
      the internal radius. The model gives valid results for spatial velocity
      distributions, which provide important information for wave propagation. 

PMID- 24935120
TI  - Genetics: Fracture risk in acromegaly.

PMID- 24935121
TI  - Therapy: Statin potency is associated with risk of new-onset diabetes in patients
      with CVD.

PMID- 24935119
TI  - Obesity and cancer--mechanisms underlying tumour progression and recurrence.
AB  - Over the past several years, the field of cancer research has directed increased
      interest towards subsets of obesity-associated tumours, which include mammary,
      renal, oesophageal, gastrointestinal and reproductive cancers in both men and
      women. The increased risk of breast cancer that is associated with obesity has
      been widely reported; this has drawn much attention and as such, warrants
      investigation of the key mechanisms that link the obese state with cancer
      aetiology. For instance, the obese setting provides a unique adipose tissue
      microenvironment with concomitant systemic endocrine alterations that favour both
      tumour initiation and progression. Major metabolic differences exist within
      tumours that distinguish them from non-transformed healthy tissues. Importantly,
      considerable metabolic differences are induced by tumour cells in the stromal
      vascular fraction that surrounds them. The precise mechanisms that underlie the
      association of obesity with cancer and the accompanying metabolic changes that
      occur in the surrounding microenvironment remain elusive. Nonetheless, specific
      therapeutic agents designed for patients with obesity who develop tumours are
      clearly needed. This Review discusses recent advances in understanding the
      contributions of obesity to cancer and their implications for tumour treatment. 

PMID- 24935124
TI  - Keys to the species of Neolebouria Gibson, 1976 (Digenea: Opecoelidae:
      Plagioporinae), with a redescription of Neolebouria truncata (Linton, 1940).
AB  - Three keys to the species of Neolebouria Gibson, 1976, representing three body
      types, are provided based on the location of the genital pore relative to the
      intestinal bifurcation. These are: the lanceolata body type, where the genital
      pore is clearly prebifurcal; the diacopae body type, where the genital pore is
      located at or near the level of the intestinal bifurcation; and the maorum body
      type, where the genital pore is clearly postbifurcal. Fifteen species were
      assigned to the lanceolata body type; eight species to the diacopae body type;
      and four species to the maorum body type. Neolebouria truncata (Linton, 1940) is
      redescribed and N. georgiensis Gibson, 1976 is reinstated as a valid species.
      Neither N. georgiensis, nor N. antarctica Szidat & Graefe, 1967 (syn. Crassicutis
      antarcticus Szidat & Graefe, 1967), as described by Zdzitowiecki et al. (1993),
      represent N. antarctica, as originally described, and N. georgiensis and N.
      antarctica, as described by Zdzitowiecki et al. (1993), may be conspecific. 

PMID- 24935123
TI  - Monorchiid trematodes of the painted sweetlips, Diagramma labiosum (Perciformes:
      Haemulidae), from the southern Great Barrier Reef, including a new genus and
      three new species.
AB  - Five monorchiid species are reported from Diagramma labiosum Macleay
      (Perciformes: Haemulidae) collected from Heron Island on the southern Great
      Barrier Reef (GBR): two described species, Helicometroides longicollis Yamaguti,
      1934 and Diplomonorchis kureh Machida, 2005 and three new species, including one
      new genus, Asymmetrostoma heronensis n. g., n. sp., Lasiotocus arrhichostoma n.
      sp. and Proctotrema addisoni n. sp. Helicometroides longicollis and D. kureh were
      previously reported from the closely related species Diagramma pictum (Thunberg)
      from Japan. Two further monorchiid species known from D. pictum, Genolopa
      plectorhynchi (Yamaguti, 1934) and Paraproctotrema fusiforme Yamaguti, 1934,
      appear to be absent from the southern Great Barrier Reef. Previous reports of two
      other monorchiids from D. labiosum from the GBR, Paramonorcheides pseudocaranxi
      Dove & Cribb, 1998 and Helicometroides vitellosus (Durio & Manter, 1968), are
      shown to have been made in error. The high richness of monorchiids and other
      trematode families in D. labiosum is consistent with that seen in other haemulids
      elsewhere. 

PMID- 24935125
TI  - Syringophilid mites (Acari: Syringophilidae) associated with the rails (Aves:
      Rallidae) and a key to the species of the genus Rafapicobia Skoracki, 2011.
AB  - The fauna of quill mites of the family Syringophilidae Lavoipierre, 1953 (Acari:
      Prostigmata Cheyletoidea) parasitising birds of the family Rallidae Vigors
      (Gruiformes) is updated. A new species, Rafapicobia melzeri n. sp. (subfamily
      Picobiinae), is described from four host species: Rallus aquaticus Linnaeus (type
      host) from Germany, Pardirallus sanguinolentus (Swainson) from Chile, Porzana
      porzana (Linnaeus) from France and P. parva (Scopoli) from Kirghizia. The new
      species is most similar to R. lepidocolaptesi Skoracki & Solarczyk, 2012 but
      differs in the absence of agenital plates and the length ratios of setae ag2:g1
      and vi:ve:si in females and in the punctate ornament on the hysteronotal and the
      pygidial shields in males. A key to the species of the genus Rafapicobia is
      proposed. This is the first record of a representative of the subfamily
      Picobiinae on gruiform birds. Additionally, new rallid hosts are reported for
      Charadriphilus ralli Skoracki & Bochkov, 2010 (subfamily Syringophilinae):
      Gallinula melanops (Vieillot) from Chile, Laterallus melanophaius (Vieillot) from
      Paraguay, and P. parva (Scopoli) from Kirghizia. 

PMID- 24935122
TI  - Possible fetal determinants of male infertility.
AB  - Although common reproductive problems, such as male infertility and testicular
      cancer, present in adult life, strong evidence exists that these reproductive
      disorders might have a fetal origin. The evidence is derived not only from large
      epidemiological studies that show birth-cohort effects with regard to testicular
      cancer, levels of testosterone and semen quality, but also from histopathological
      observations. Many infertile men have histological signs of testicular
      dysgenesis, including Sertoli-cell-only tubules, immature undifferentiated
      Sertoli cells, microliths and Leydig cell nodules. The most severe gonadal
      symptoms occur in patients with disorders of sexual development (DSDs) who have
      genetic mutations, in whom even sex reversal of individuals with a 46,XY DSD can
      occur. However, patients with severe DSDs might represent only a small proportion
      of DSD cases, with milder forms of testicular dysgenesis potentially induced by
      exposure to environmental and lifestyle factors. Interestingly, maternal smoking
      during pregnancy has a stronger effect on spermatogenesis than a man's own
      smoking. Other lifestyle factors such as alcohol consumption and obesity might
      also have a role. However, increasing indirect evidence exists that exposure to
      ubiquitous endocrine disrupting chemicals, present at measurable concentrations
      in individuals, might affect development of human fetal testis. If confirmed,
      health policies to prevent male reproductive problems should not only target
      adult men, but also pregnant women and their children. 

PMID- 24935126
TI  - A new species of Bathycreadium Kabata, 1961 (Digenea: Opecoelidae) from Phycis
      blennoides (Brunnich) (Gadiformes: Phycidae) in the western Mediterranean.
AB  - Bathycreadium brayi n. sp. is described based on specimens collected from the
      deep-sea greater forkbeard Phycis blennoides (Brunnich) (Gadiformes: Phycidae) in
      the Western Mediterranean. The new species is distinguished from B. flexicolle
      Kabata, 1961, B. elongata (Maillard, 1970) and B. nanaflexicolle Dronen, Rubec &
      Underwood, 1977 by the much smaller size of the body and most organs, the large
      (in relation to body length and width) ventral sucker and the distinctly more
      anterior extent of the vitelline fields and from B. biscayense Bray, 1973 in
      having a narrower body, longer forebody and oesophagus, distinctly smaller
      ventral sucker and sucker width ratio and the shape of the gonads. Re-examination
      of the type-material of B. biscayense revealed that the original description of
      this species is based on composite material. A redescription of B. biscayense
      based on adult specimens from its type-host, Trachyrincus scabrus (Rafinesque),
      and new data based on the re-examination of the type-specimens of B. flexicolle
      and B. elongata are also provided. 

PMID- 24935127
TI  - Description of raabeia, synactinomyxon and neoactinomyxum developing stages of
      myxosporeans (Myxozoa) infecting Isochaetides michaelseni Lastockin (Tubificidae)
      in Lake Balaton and Kis-Balaton Water Reservoir, Hungary.
AB  - Molecular and morphometric investigations were conducted on the actinosporean
      morphotypes of myxosporeans surveyed in oligochaetes of Lake Balaton and Kis
      Balaton Water reservoir. Oligochaetes belonging to the species Isochaetides
      michaelseni Lastockin and Branchiura sowerbyi Beddard as well as to the genera
      Nais Dujardin, Dero Muller and Aeolosoma Ehrenberg were studied during an 18
      month period. Actinosporeans were obtained exclusively from I. michaelseni (7,818
      specimens) with very low prevalence (0.01-0.06%). Four new actinosporean
      morphotypes of the collective groups raabeia (2 types), synactinomyxon (1 type)
      and neoactinomyxum (1 type) were found and described, including the first
      synactinomyxon collective group from Hungarian biotopes and a new raabeia
      morphotype. Except for Synactinomyxon type 1, the 18S rDNA analysis revealed that
      the spores did not match any myxospore entity found in the GenBank. 

PMID- 24935128
TI  - Amblyomma hadanii n. sp. (Acari: Ixodidae), a tick from northwestern Argentina
      previously confused with Amblyomma coelebs Neumann, 1899.
AB  - All stages of Amblyomma hadanii n. sp. (Acari: Ixodidae) are described from
      northwestern Argentina. The diagnostic characters for males are a combination of
      the pattern of scutal ornamentation, basis capituli dorsally rectangular with
      cornua, coxa I with two subequal spurs (the internal wider, the external longer),
      coxae II-III with a single spur, coxa IV with a single spur not reaching level of
      anus, ventral plates irregular in shape (larger and sometimes with a small
      incision on festoons 4, 5 and 6) and hypostome spatulate with dental formula 3/3
      in 7-8 rows. The diagnostic characters for the females are a combination of
      scutal ornamentation, postero-lateral margins of scutum slightly convex, coxa I
      with two subequal spurs (the internal wider, the external longer), basis capituli
      dorsally rectangular, porose areas rounded, genital aperture U-shaped, and
      hypostome spatulate with dental formula 3/3 in 7-8 rows. Diagnosis of nymphs can
      be performed by a combination of basis capituli rectangular, scutum with large
      punctations in the lateral fields and small punctations in the central field, and
      cervical groove short and ending as a small shallow depression at the eye level.
      Larvae are diagnosed by the shape of basis capituli, scutum with with posterior
      margin slightly convex, and legs with coxa I with 2 triangular spur (the external
      longer than the internal), and with coxae II and III each with 1 triangular spur.
      The hosts recorded for this new tick species are Tapirus terrestris (Linnaeus),
      horse, cattle, dog and humans. Analyses of a 410 bp fragment of the mitochondrial
      16S rRNA gene and the complete sequence of the nuclear 18S rRNA gene supported
      the description of A. hadanii as a new species.

PMID- 24935129
TI  - A new species of Parapanteles Ashmead, 1900 (Hymenoptera: Braconidae:
      Microgastrinae) parasitic on Charaxes athamas (Drury) (Lepidoptera: Nymphalidae)
      in India.
AB  - A new species of gregarious endoparasitoid, Parapanteles athamasae n. sp.
      (Hymenoptera: Braconidae), parasitising caterpillars of Charaxes athamas (Drury)
      (Lepidoptera: Nymphalidae) on the host plant Senegalia catechu (=Acacia catechu)
      (L.f.) Hurter & Mabb., is described from Maharashtra, India. Diagnostic
      characters of the new species include: propodeum with areola 0.93* longer than
      wide, legs yellow, hind tibia 4.30* as long as ovipositor, ovipositor sheaths
      exerted, first metasomal tergal plate 1.24* longer than wide, with coarse
      sculpture merging with longitudinal striations at 3/4 of the apical region. This
      is the first time a species of the family Nymphalidae Rafinesque is recorded in
      association with Parapanteles Ashmead, 1900. A key to the Indian species of
      Parapanteles based on females is also provided. 

PMID- 24935130
TI  - A new species of chondracanthid copepod parasitic in the pharynx of hagfishes
      (Myxiniformes: Myxinidae) from off Taiwan.
AB  - A new species of Acanthochondria Oakley, 1927 (Copepoda, Poecilostomatoida,
      Chondracanthidae), parasitic in the pharynx of hagfishes Eptatretus burgeri
      (Girard), E. sheni (Kuo, Huang & Mok) and E. yangi (Teng), from off Taiwan is
      described and illustrated. The new species can be distinguished from its
      congeners by having the neck region longer than wide (about 2-3 times as long as
      wide), the moderately long protopod of leg 2 (Type E), the endopod of leg 2 as
      large as exopod, the cephalosome wider than long, the armature formula of
      antennule (1, 1, 2, 2, 9), the relatively long trunk (6.7 mm) and egg-sacs (14.4
      mm). This is the first record of a parasitic chondracanthid from hagfishes. The
      findings may provide insights into the phylogenetic relationships and
      interactions among chondracanthids, hagfishes and demersal fishes, but call for
      further molecular studies.

PMID- 24935131
TI  - Block-step asymmetry 5 years after large-head metal-on-metal total hip
      arthroplasty is related to lower muscle mass and leg power on the implant side.
AB  - BACKGROUND: Metal-on-metal articulations mimic the human hip anatomy, presumably
      lower dislocation rates and increase the range-of-motion. This study aims to
      measure the muscle mass and power of both legs in patients with unilateral metal
      on-metal total hip arthroplasty, and to investigate their effect on block-step
      test, spatio-temporal gait parameters and self-reported function. METHODS: Twenty
      eight patients (7 women), mean age 50 (28-68) years, participated in a 5-7 year
      follow-up. Patients had received one type unilateral large-head metal-on-metal
      total hip articulation, all of which were well-functioning at follow-up. Mean
      muscle mass was measured by the total-body Dual energy X-ray Absorption scans,
      and muscle power was measured in a leg extensor power rig. Block-step test and
      spatio-temporal gait parameters were measured with an inertial measurement unit.
      Self-reported function was assessed by the Hip Disability and Osteoarthritis
      Outcome Score. FINDINGS: We found a significant difference between the mean
      muscle mass of the implant-side leg and the non-implant-side leg in hip, thigh
      and calf areas (P<0.008) and in mean muscle power (P=0.025). Correlations between
      mean muscle mass and mean muscle power were significant for both the implant-side
      leg (r=0.45, P=0.018) and the non-implant-side leg (r=0.51, P=0.007). The
      difference in mean muscle power between legs correlated with block-step test
      asymmetry during ascending (r=0.40, P=0.047) and descending (r=0.53, P=0.006).
      Correlations between self-reported function and power of the implant-side leg
      were not significant. INTERPRETATIONS: Young patients have not fully regained
      muscle mass, muscle power and function 5-7 years after metal-on-metal total hip
      arthroplasty.

PMID- 24935132
TI  - Energy-efficient green catalysis: supported gold nanoparticle-catalyzed
      aminolysis of esters with inert tertiary amines by C-O and C-N bond activations.
AB  - Catalyzed by supported gold nanoparticles, an aminolysis reaction between various
      aryl esters and inert tertiary amines by C-O and C-N bond activations has been
      developed for the selective synthesis of tertiary amides. Comparison studies
      indicated that the gold nanoparticles could perform energy-efficient green
      catalysis at room temperature, whereas Pd(OAc)2 could not. 

PMID- 24935133
TI  - The Legacy of Nelson Mandela: Impact on Transcultural Health Care.

PMID- 24935134
TI  - Enhancing Nurses' Ability to Care Within the Culture of Incarceration.
AB  - Incarcerated women are a highly vulnerable population, most of whom have had
      extremely adverse life experiences. Nurses who work in corrections have
      significant challenges as they attempt to care in a setting that is focused on
      punishment. This article focuses on the unique culture of incarceration as it
      applies to women, along with the common challenges nurses face when caring for
      these women. Leininger's Theory of Culture Care and the Sunrise Enabler are
      discussed as useful tools to assist nurses in providing culture care within the
      confines of the prison, as well as a means of understanding these women as
      cultural beings apart from the prison setting. Despite the many security
      restrictions that exist within the correctional environment, "care" can be
      provided regardless of the setting. A model case has been developed to show the
      enormous impact that culture care can have on the lives of many women who face
      incarceration. 

PMID- 24935135
TI  - Transcultural Nursing Scholars' Corner: Sages, Storytellers, and Scholars.

PMID- 24935136
TI  - Community-based abstinence education project: program outcomes.
AB  - PROBLEM: Middle school and adolescent populations demonstrate high rates of
      unintended pregnancies and sexually transmitted infections, with young people in
      inner cities in the United States especially vulnerable. Teen births remain high,
      and youth are affected physically, mentally, socially, and economically. METHODS:
      The Sex After Marriage primary prevention program, a federally funded, community
      based abstinence education (CBAE) initiative, was implemented for 3 years in
      Philadelphia neighborhoods with vulnerable youth 12 to 18 years of age,
      supporting adults, healthcare professionals, and the general public. The three
      tiered program offered a middle school curriculum, Sex Can Wait, at 16 different
      sites. The CBAE program delivered by the university's nursing center attempted to
      support vulnerable youths' decisions to postpone sexual activity by matching the
      interests of young people through an established curriculum, by holding workshops
      for supporting adults, and by creating a multimedia approach to supplement
      abstinence education initiatives including public service announcements and a
      website. Youth and college ambassadors and community colleagues were trained in
      the curriculum with a focus on healthy lifestyles. Youth and parents in
      experimental and control groups completed self-report surveys before and after
      program implementation. FINDINGS: The project achieved most of its objectives on
      program evaluation. Youth (n = 1,428) 12 to 18 years of age received services,
      with most completing >=75% of the program. Parents (n = 338) and other
      participating adults (n = 486) also received education or services. CONCLUSIONS:
      The need for risk reduction programs persists for youth in light of pregnancy,
      birth, and sexually transmitted disease statistics. Bailey Wolf.

PMID- 24935137
TI  - Multimodality imaging of cardiothoracic lymphoma.
AB  - Lymphoma is the most common hematologic malignancy and represents approximately
      5.3% of all cancers. The World Health Organization published a revised
      classification scheme in 2008 that groups lymphomas by cell type and molecular,
      cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at
      some stage during the course of the disease. Affected structures within the chest
      may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may
      originate from these sites as primary malignancies or secondarily involve these
      structures after arising from other intrathoracic or extrathoracic sources.
      Pulmonary lymphomas are classified into one of four types: primary pulmonary
      lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome
      related lymphoma, and post-transplantation lymphoproliferative disorders.
      Although pulmonary lymphomas may produce a myriad of diverse findings within the
      lungs, specific individual features or combinations of features can be used, in
      combination with secondary manifestations of the disease such as involvement of
      the mediastinum, pleura, and chest wall, to narrow the differential diagnosis.
      While findings of thoracic lymphoma may be evident on chest radiography, computed
      tomography has traditionally been the imaging modality used to evaluate the
      disease and effectively demonstrates the extent of intrathoracic involvement and
      the presence and extent of extrathoracic spread. However, additional modalities
      such as magnetic resonance imaging of the thorax and (18)F-FDG PET/CT have
      emerged in recent years and are complementary to CT in the evaluation of patients
      with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest
      wall involvement, and PET/CT is more accurate in the overall staging of lymphoma
      than CT and can be used to evaluate treatment response. 

PMID- 24935138
TI  - Response to "a note on the mapping and quantification of the human brain
      corticospinal tract".

PMID- 24935139
TI  - Lumbosacral transitional vertebra in a population-based study of 5860
      individuals: prevalence and relationship to low back pain.
AB  - PURPOSE: To investigate the prevalence of lumbosacral transitional vertebra
      (LSTV) within the Chinese Han population, and to determine whether LSTV
      correlates with low back pain (LBP) and gluteal pain. MATERIALS AND METHODS:
      Typical standing pelvic radiographs were obtained for 5860 volunteers between 18
      to 60 years of age. The lumbosacral region of each spine was evaluated to
      identify LSTV, which was classified into types I, II, III, and IV based on
      Castellvi's method. Histories of low back symptoms were obtained using a
      questionnaire. The association of different subtypes of LSTV with LBP and gluteal
      pain was explored. RESULTS: LSTV was found in 15.8% (928 of 5860) of our study
      population. Of the 928 individuals with LSTV, 44.8% were type I (dysplastic
      transverse process with height >19mm), 43.2% were type II (pseudoarticulation),
      7.2% were type III (fusion), and 4.8% were type IV (a unilateral type II
      transition with a type III fusion on the contralateral side). Type II LSTV were
      closely associated with LBP and gluteal pain, with respective odds ratios (ORs)
      of 2.56 (95% CI: 2.17-3.89) and 5.38 (95% CI: 4.29-8.43). Similarly, types IV
      LSTV also demonstrated a significant correlation with LBP and gluteal pain, with
      respective ORs of 4.28 (95% CI: 3.21-6.35) and 6.82 (95% CI: 5.17-16.59).
      CONCLUSIONS: In this population-based study, the prevalence of LSTV was 15.8%,
      with type I being the most common. Importantly, LSTV types II and IV were
      significantly associated with LBP and gluteal pain.

PMID- 24935141
TI  - The value of dental hygiene research conferences.

PMID- 24935140
TI  - Dual-phase CT findings of groove pancreatitis.
AB  - PURPOSE: Groove pancreatitis is a rare focal form of chronic pancreatitis that
      occurs in the pancreaticoduodenal groove between the major and minor papillae,
      duodenum and pancreatic head. Radiologic appearance and clinical presentation can
      result in suspicion of malignancy rendering pancreaticoduodenectomy inevitable.
      This study reports dual phase CT findings in a series of 12 patients with
      pathology proven groove pancreatitis. MATERIALS AND METHODS: Retrospective review
      of preoperative CT findings in 12 patients with histologically proven groove
      pancreatitis after pancreaticoduodenectomy. Size, location, attenuation, presence
      of mass or cystic components in the pancreas, groove and duodenum,
      calcifications, duodenal stenosis and ductal changes were recorded. Clinical
      data, laboratory values, endoscopic ultrasonographic and histopathological
      findings were collected. RESULTS: Soft tissue thickening in the groove was seen
      in all patients. Pancreatic head, groove and duodenum were all involved in 75%
      patients. A discrete lesion in the pancreatic head was seen in half of the
      patients, most of which appeared hypodense on both arterial and venous phases.
      Cystic changes in pancreatic head were seen in 75% patients. Duodenal involvement
      was seen in 92% patients including wall thickening and cyst formation. The main
      pancreatic duct was dilated in 7 patients, with an abrupt cut off in 3 and a
      smooth tapering stricture in 4. Five patients had evidence of chronic
      pancreatitis with parenchymal calcifications. CONCLUSION: Presence of mass or
      soft tissue thickening in the groove with cystic duodenal thickening is highly
      suggestive of groove pancreatitis. Recognizing common radiological features may
      help in diagnosis and reduce suspicion of malignancy.

PMID- 24935142
TI  - Antimicrobial resistance--the global threat: state of the science.

PMID- 24935143
TI  - Considerations for treating women with cancer.

PMID- 24935144
TI  - Thirty years of HIV/AIDS and related oral manifestations and management.

PMID- 24935145
TI  - Medical and dental implications of eating disorders.

PMID- 24935146
TI  - A qualitative study of extended care permit dental hygienists in Kansas.
AB  - PURPOSE: Currently, 37 states allow some type of alternative practice settings
      for dental hygienists. This qualitative study was designed to explore the
      experiences of the Extended Care Permit (ECP) dental hygienist in the state of
      Kansas. As a first ever study of this workforce model, a qualitative research
      design was chosen to illuminate the education and experiences of extended dental
      hygiene practitioners in order to understand the impact ECP legislation has had
      on increasing the public's access to oral health care services and define the
      advantages and limitation of this model as one potential solution to access to
      oral care. Snowball sampling was used to identify study participants who were
      actively engaged in extended care practice. Nine subjects, which included one ECP
      consultant and eight ECP providers, participated in this study. Data obtained via
      personal interviews and through document analysis data were subsequently coded
      and thematically analyzed by three examiners. An independent audit was conducted
      by a fourth examiner to confirm dependability of results. Seven major categories
      emerged from the data analysis: entrepreneur dental hygienist, partnerships,
      funding, barriers, sustainability, models of care and the impact of the ECP. The
      findings of this study revealed that ECP hygienists are making an impact with
      underserved populations, primarily children, the elderly and special needs
      patients.

PMID- 24935147
TI  - A racial comparison of sociocultural factors and oral health perceptions.
AB  - PURPOSE: There are limited data regarding race, sociocultural factors and dental
      outcomes such as oral health perceptions. The purpose of this study is to
      recognize and determine whether sociocultural factors impact oral health
      practices, and how these relate to oral health care perceptions among African
      American (AA) and Asian American (AS) comparison groups. METHODS: In this cross
      sectional study, participants were selected using a purposive sampling technique
      among new enrolling patients of AA and AS origin at the New York University
      College of Dentistry (NYUCD). Sociocultural factors such as low education level,
      poor access to care, limited financial status and perceptions of oral health such
      as brushing and flossing were studied. RESULTS: Among 139 participants, 86
      (61.87%) were AA and 53 (38.13%) were AS. Compared to AS, AA had poorer access to
      care (58.14% vs. 43.40%, p<0.01) and cost was a greater financial barrier for
      dental care (41.86% vs. 26.41%, p<0.01). Race was the strongest predictor of oral
      health perceptions (OR =2.27, p<0.05) followed by limited financial status (OR
      =1.335 p<0.05) and poor access to care (OR =1.299 p<0.01). AA had more adverse
      oral health perceptions (83.72% vs. 69.81%, p<0.05), higher incidence of dental
      decay (13.95% vs 7.54%, p<0.05) and mixed disease (dental decay and periodontal
      disease) (88.37% vs. 60.37%, p<0.05) compared to AS. There was no difference in
      oral health practices (brushing and flossing) between the two populations.
      CONCLUSION: AA had more adverse oral health perceptions and higher incidence of
      dental disease than AS. Cultural influences have an impact on perceptions and
      behaviors that may affect oral health. Therefore, cultural awareness and
      competency among oral health professionals should be emphasized.

PMID- 24935148
TI  - In vitro effect of over-the-counter probiotics on the ability of Candida albicans
      to form biofilm on denture strips.
AB  - PURPOSE: There is a burgeoning recognition and interest in the potential of
      probiotics in the treatment and prevention of oral candidiasis associated with
      the use of dentures. Our aim was to investigate if commercially available over
      the-counter probiotics can influence the ability of Candida albicans to form
      biofilms, which is considered a hallmark of the initiation and progression of
      oral candidiasis. METHODS: We conducted a 2*5 factorial in vitro study to culture
      C. albicans on denture strips and challenge with one of the following four
      commercially available probiotics in bacterial or cell-free supernatant form:
      Accuflora(r), Align(r), Culturelle(r) and Sustenex(r). C. albicans biofilm
      formation was studied in triplicates in all factorial combinations of the study
      and assessed qualitatively with fluorescence microscopy and quantitatively with
      tetrazolium salt (XTT) reduction assay. Quality control measures included
      determination of coefficient of variation, Bland Altman plots and Pittman's test.
      Results were analyzed using two-way analysis of variance (ANOVA) with pairwise
      post-hoc Scheffe's tests. RESULTS: Our experimental conditions passed the quality
      control checks. Two-way ANOVA results indicated that cell-free supernatants
      provided a stronger and significant inhibitory effect on biofilm formation than
      their bacterial counterparts (2-way ANOVA p=3.8*10(-6)). Further, Lactobacillus
      containing probiotic formulations (Accuflora(r) and Culturelle(r)) significantly
      reduced biofilm formation especially in supernatant form. CONCLUSION:
      Commercially available probiotics that contain Lactobacilli species interfere
      with the in vitro ability of C. albicans to form biofilms on dentures. The
      mechanistic and clinical implications of our results need to be addressed by
      larger in vivo studies.

PMID- 24935149
TI  - Fast, simple, and sensitive high-performance liquid chromatography method for
      measuring vitamins A and E in human blood plasma.
AB  - Vitamins A and E are fat-soluble vitamins that play important roles in several
      physiological processes. Monitoring their concentrations is needed to detect
      deficiency and guide therapy. In this study, we developed a high-performance
      liquid chromatography method to measure the major forms of vitamin A (retinol)
      and vitamin E (alpha-tocopherol and gamma-tocopherol) in human blood plasma.
      Vitamins A and E were extracted with hexane and separated on a reversed-phase
      column using methanol as the mobile phase. Retinol was detected by ultraviolet
      absorption, whereas tocopherols were detected by fluorescence emission. The
      chromatographic cycle time was 4.0 min per sample. The analytical measurement
      range was 0.03-5.14, 0.32-36.02, and 0.10-9.99 mg/L for retinol, alpha
      tocopherol, and gamma-tocopherol, respectively. Intr-aassay and total coefficient
      of variation were <6.0% for all compounds. This method was traceable to standard
      reference materials offered by the National Institute of Standards and
      Technology. Reference intervals were established using plasma samples collected
      from 51 healthy adult donors and were found to be 0.30-1.20, 6.0-23.0, and 0.3
      3.2 mg/L for retinol, alpha-tocopherol, and gamma-tocopherol, respectively. In
      conclusion, we developed and validated a fast, simple, and sensitive high
      performance liquid chromatography method for measuring the major forms of
      vitamins A and E in human plasma.

PMID- 24935150
TI  - Design of tissue engineering scaffolds based on hyperbolic surfaces: structural
      numerical evaluation.
AB  - Tissue engineering represents a new field aiming at developing biological
      substitutes to restore, maintain, or improve tissue functions. In this approach,
      scaffolds provide a temporary mechanical and vascular support for tissue
      regeneration while tissue in-growth is being formed. These scaffolds must be
      biocompatible, biodegradable, with appropriate porosity, pore structure and
      distribution, and optimal vascularization with both surface and structural
      compatibility. The challenge is to establish a proper balance between porosity
      and mechanical performance of scaffolds. This work investigates the use of two
      different types of triple periodic minimal surfaces, Schwarz and Schoen, in order
      to design better biomimetic scaffolds with high surface-to-volume ratio, high
      porosity and good mechanical properties. The mechanical behaviour of these
      structures is assessed through the finite element method software Abaqus. The
      effect of two parametric parameters (thickness and surface radius) is also
      evaluated regarding its porosity and mechanical behaviour. 

PMID- 24935151
TI  - Left anterior descending coronary artery blood flow and left ventricular
      unloading during extracorporeal membrane oxygenation support in a swine model of
      acute cardiogenic shock.
AB  - The impact of extracorporeal membrane oxygenation (ECMO) support on coronary
      blood flow and left ventricular unloading is still debated. This study aimed to
      further characterize the influence of ECMO on coronary artery blood flow and its
      ability to unload the left ventricle in a short-term model of acute cardiogenic
      shock. Seven anesthetized pigs were intubated and then underwent median
      sternotomy and cannulation for venoarterial (VA) ECMO. Flow in the left anterior
      descending (LAD) artery, left atrial pressure (LAP), left ventricular end
      diastolic pressure (LVEDP), and mean arterial pressure (MAP) were measured before
      and after esmolol-induced cardiac dysfunction and after initiating VA-ECMO
      support. Induction of acute cardiogenic shock was associated with short-term
      increases in LAP from 8 +/- 4 mm Hg to 18 +/- 14 mm Hg (P = 0.9) and LVEDP from 5
      +/- 2 mm Hg to 13 +/- 17 mm Hg (P = 0.9), and a decrease in MAP from 63 +/- 16 mm
      Hg to 50 +/- 24 mm Hg (P = 0.3). With VA-ECMO support, blood flow in the LAD
      increased from 28 +/- 25 mL/min during acute unsupported cardiogenic shock to 67
      +/- 50 mL/min (P = 0.003), and LAP and LVEDP decreased to 8 + 5 mm Hg (P = 0.7)
      and 5 +/- 3 mm Hg (P = 0.5), respectively. In this swine model of acute
      cardiogenic shock, VA-ECMO improved coronary blood flow and provided some degree
      of left ventricular unloading for the short duration of the study. 

PMID- 24935152
TI  - Quantification of skeletal asymmetries in normal adolescents: cone-beam computed
      tomography analysis.
AB  - BACKGROUND: The detection and quantification of skeletal asymmetries is a
      fundamental component to diagnosis and treatment planning in orthodontics. The
      purpose of this study was to identify and quantify the characteristics of facial
      and dental asymmetries in a normal, adolescent population using 3D imaging.
      METHODS: Thirty consecutive Class I patients (mean age 14.32 years, SD 1.67)
      meeting the inclusion criteria were analyzed by three-dimensional cone-beam
      computed tomography (CBCT). Dental, maxillary, mandibular, and cranial base
      variables were measured with Dolphin 3D. CBCT analysis consisted of the
      localization of 34 anatomical landmarks. All reference points were digitized in
      3D and analyzed using 67 skeletal and dental measurements. Student's t tests for
      paired samples were used with a significance level of p < 0.05. RESULTS: Minor
      right-left discrepancies were noted in all planes. The most anterior point of the
      glenoid fossa and most condylar points were positioned more superior and lateral
      on the right side, compared to the left side. Porion was also located more
      superiorly on the right side relative to the left side. The posterior nasal spine
      was found to be located to the right of the midsagittal plane. Slight dental
      midline discrepancies were found, and the dental arch lengths were slightly
      longer on the left side compared to the right. The height of the ramus, in both
      3D and 2D, and the inclination of the ramus were greater on the right than that
      on the left side. CONCLUSIONS: The findings of this study suggest minor
      asymmetries exist and are likely a common occurrence in the normal human
      craniofacial complex. Additionally, a natural compensatory mechanism may exist
      which controls the size and shape of specific tissues in order to maintain
      functional symmetry.

PMID- 24935153
TI  - Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and
      anticancer efficacy.
AB  - BACKGROUND: Andrographolide (ADG) isolated from Andrographis paniculata exhibits
      anti-inflammatory and anticancer activities, but high hydrophobicity and poor
      bioavailability greatly restricts its clinical application. OBJECTIVES: In this
      study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide
      co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA
      PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer
      efficacy and bioavailability in vivo. METHODS: The physicochemical properties of
      the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation
      efficiency, particle size, zeta potential and critical micelle concentration.
      These micelles were further evaluated for in vitro cytotoxicity, including
      proliferation inhibition, cell cycle arrest and pro-apoptosis effects against
      human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study
      in rat. RESULTS: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and
      loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable
      particle size of 124.3 +/- 6.4 nm. In vitro cytotoxicity testing demonstrated
      that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition,
      cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231
      cells, which would be contributed to higher efficiency of cellular uptake and
      intracellular transport. Further, the plasma AUC(0 - infinity) and mean resident
      time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold,
      respectively, when compared to the raw suspension. CONCLUSION: All of these
      investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug
      delivery strategy for improving ADG bioavailability and efficacy in cancer
      therapy.

PMID- 24935154
TI  - Molecular basis of gain-of-function LEOPARD syndrome-associated SHP2 mutations.
AB  - The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2)
      is a critical signal transducer downstream of growth factors that promotes the
      activation of the RAS-ERK1/2 cascade. In its basal state, SHP2 exists in an
      autoinhibited closed conformation because of an intramolecular interaction
      between its N-SH2 and protein tyrosine phosphatase (PTP) domains. Binding to pTyr
      ligands present on growth factor receptors and adaptor proteins with its N-SH2
      domain localizes SHP2 to its substrates and frees the active site from allosteric
      inhibition. Germline mutations in SHP2 are known to cause both Noonan syndrome
      (NS) and LEOPARD syndrome (LS), two clinically similar autosomal dominant
      developmental disorders. NS-associated SHP2 mutants display elevated phosphatase
      activity, while LS-associated SHP2 mutants exhibit reduced catalytic activity. A
      conundrum in how clinically similar diseases result from mutations to SHP2 that
      have opposite effects on this enzyme's catalytic functionality exists. Here we
      report a comprehensive investigation of the kinetic, structural, dynamic, and
      biochemical signaling properties of the wild type as well as all reported LS
      associated SHP2 mutants. The results reveal that LS-causing mutations not only
      affect SHP2 phosphatase activity but also induce a weakening of the
      intramolecular interaction between the N-SH2 and PTP domains, leading to mutants
      that are more readily activated by competing pTyr ligands. Our data also indicate
      that the residual phosphatase activity associated with the LS SHP2 mutant is
      required for enhanced ERK1/2 activation. Consequently, catalytically impaired
      SHP2 mutants could display gain-of-function properties because of their ability
      to localize to the vicinity of substrates for longer periods of time, thereby
      affording the opportunity for prolonged substrate turnover and sustained RAS
      ERK1/2 activation. 

PMID- 24935155
TI  - The use of induced pluripotent stem cells to reveal pathogenic gene mutations and
      explore treatments for retinitis pigmentosa.
AB  - BACKGROUND: Retinitis pigmentosa (RP) is an inherited human retinal disorder that
      causes progressive photoreceptor cell loss, leading to severe vision impairment
      or blindness. However, no effective therapy has been established to date.
      Although genetic mutations have been identified, the available clinical data are
      not always sufficient to elucidate the roles of these mutations in disease
      pathogenesis, a situation that is partially due to differences in genetic
      backgrounds. RESULTS: We generated induced pluripotent stem cells (iPSCs) from an
      RP patient carrying a rhodopsin mutation (E181K). Using helper-dependent
      adenoviral vector (HDAdV) gene transfer, the mutation was corrected in the
      patient's iPSCs and also introduced into control iPSCs. The cells were then
      subjected to retinal differentiation; the resulting rod photoreceptor cells were
      labeled with an Nrl promoter-driven enhanced green fluorescent protein (EGFP)
      carrying adenovirus and purified using flow cytometry after 5 weeks of culture.
      Using this approach, we found a reduced survival rate in the photoreceptor cells
      with the E181K mutation, which was correlated with the increased expression of
      endoplasmic reticulum (ER) stress and apoptotic markers. The screening of
      therapeutic reagents showed that rapamycin, PP242, AICAR, NQDI-1, and salubrinal
      promoted the survival of the patient's iPSC-derived photoreceptor cells, with a
      concomitant reduction in markers of ER stress and apoptosis. Additionally,
      autophagy markers were found to be correlated with ER stress, suggesting that
      autophagy was reduced by suppressing ER stress-induced apoptotic changes.
      CONCLUSION: The use of RP patient-derived iPSCs combined with genome editing
      provided a versatile cellular system with which to define the roles of genetic
      mutations in isogenic iPSCs with or without mutation and also provided a system
      that can be used to explore candidate therapeutic approaches.

PMID- 24935156
TI  - Incidence and predictors of morphometric vertebral fractures in patients with
      ankylosing spondylitis.
AB  - INTRODUCTION: Ankylosing spondylitis (AS) is associated with an increased
      incidence of vertebral fractures (VFs); however the actual incidence and
      predictors of morphometric VFs are unknown. The present study examined the
      incidence and predictors of new VFs in a large AS cohort. METHODS: In total, 298
      AS patients who fulfilled the modified New York criteria were enrolled and spinal
      radiographs were evaluated biennially. Clinical and laboratory data and
      radiographic progression were assessed according to the Bath AS Disease Activity
      Index, erythrocyte sedimentation rate, C-reactive protein (CRP), and the Stoke AS
      spine score (SASSS). VF was defined according to the Genant criteria. The
      incidence of VFs at 2 and 4 years was evaluated using the Kaplan-Meier method.
      The age-specific standardized prevalence ratio (SPR) for AS patients in
      comparison with the general population was calculated. RESULTS: Of 298 patients,
      31 (10.8%) had previous VFs at baseline. A total of 30 new VFs occurred in 26
      patients over 4 years. The incidence of morphometric VFs was 4.7% at 2 years and
      13.6% at 4 years. Multivariate logistic regression analysis showed that previous
      VFs at baseline and increased CRP levels at 2 years were predictors of new VFs
      (odds ratio (OR) =12.8, 95% confidence interval (CI) = 3.6-45.3 and OR = 5.4, 95%
      CI = 1.4-15.9). The age-specific specific standardized prevalence ratio of
      morphometric VFs in AS was 3.3 (95% CI 2.1-4.5). CONCLUSIONS: The incidence of
      morphometric VFs increased in AS. Previous VFs and increased CRP levels predicted
      future VFs. Further studies are needed to identify the effects of treatment
      interventions on the prevention of new VFs.

PMID- 24935157
TI  - Foods and food components in the Mediterranean diet: supporting overall effects.
AB  - The recent publication of the PREDIMED trial provided definitive evidence that a
      Mediterranean diet provides protection against cardiovascular disease. Two
      articles published in BMC Medicine provide further understanding of why this may
      be the case, by considering contributory effects of olive oil, a core food in the
      diet, and polyphenols, a class of identifiable protective compounds. Using a
      number of statistical models, analyses were conducted to show around a 35%
      cardiovascular disease risk reduction in the highest consumers of olive oil and a
      similar degree of risk reduction for all-cause mortality comparing highest to
      lowest quintiles of polyphenol intake. The effects were an advance on cohort
      studies not related to trials. This suggests that it may be necessary to have
      better control of the background diet to enable exposure of the value of
      individual foods and nutrients in a dietary pattern, bearing in mind that, by
      nature, it is difficult to separate out effects of foods, nutrients and whole
      diets.

PMID- 24935159
TI  - Density functional theory study on mechanisms of epoxy-phenol curing reaction.
AB  - A comprehensive picture on the mechanism of the epoxy-phenol curing reactions is
      presented using the density functional theory B3LYP/ 6-31G(d,p) and simplified
      physical molecular models to examine all possible reaction pathways. Phenol can
      act as its own promoter by using an addition phenol molecule to stabilize the
      transition states, and thus lower the rate-limiting barriers by 27.0-48.9 kJ/mol.
      In the uncatalyzed reaction, an epoxy ring is opened by a phenol with an apparent
      barrier of about 129.6 kJ/mol. In catalyzed reaction, catalysts facilitate the
      epoxy ring opening prior to curing that lowers the apparent barriers by 48.9-50.6
      kJ/mol. However, this can be competed in highly basic catalysts such as amine
      based catalysts, where catalysts are trapped in forms of hydrogen-bonded complex
      with phenol. Our theoretical results predict the activation energy in the range
      of 79.0-80.7 kJ/mol in phosphine-based catalyzed reactions, which agrees well
      with the reported experimental range of 54-86 kJ/mol.

PMID- 24935158
TI  - Enhancement of cell ingrowth, proliferation, and early differentiation in a three
      dimensional silicon carbide scaffold using low-intensity pulsed ultrasound.
AB  - Concerns over the use of autografts or allografts have necessitated the
      development of biomaterials for bone regeneration. Various studies have been
      performed to optimize the cultivation of osteogenic cells using osteoconductive
      porous scaffolds. The aim of this study was to evaluate the osteogenic efficiency
      of bone cell ingrowth, proliferation, and early differentiation in a silicon
      carbide (SiC) porous ceramic scaffold promoted with low-intensity pulsed
      ultrasound. MC3T3-E1 mouse preosteoblasts were seeded onto scaffolds and cultured
      for 4 and 7 days with daily of 20-min ultrasound treatment. The cells were
      evaluated for cell attachment, morphology, viability, ingrowth depth, volumetric
      proliferation, and early differentiation. After 4 and 7 days of culture and
      ultrasound exposure, the cell density was higher in the ultrasound-treated group
      compared with the sham-treated group on SiC scaffolds. The cell ingrowth depths
      inside the SiC scaffolds were 149.2+/-27.3 MUm at 1 day, 310.1+/-12.6 MUm for the
      ultrasound-treated group and 248.0+/-19.7 MUm for the sham control at 4 days, and
      359.6+/-18.5 MUm for the ultrasound-treated group and 280.0+/-17.7 MUm for the
      sham control at 7 days. They were significantly increased, that is, 25%
      (p=0.0029) and 28% (p=0.0008) increase, respectively, with ultrasound radiation
      force as compared with those in sham control at 4 and 7 days postseeding. The
      dsDNA contents were 583.5+/-19.1 ng/scaffold at 1 day, 2749.9+/-99.9 ng/scaffold
      for the ultrasound-treated group and 2514.9+/-114.7 ng/scaffold for the sham
      control at 4 days, and 3582.3+/-325.3 ng/scaffold for the ultrasound-treated
      group and 2825.7+/-134.3 ng/scaffold for the sham control at 7 days. There was a
      significant difference in the dsDNA content between the ultrasound- and sham
      treated groups at 4 and 7 days. The ultrasound-treated group with the SiC
      construct showed a 9% (p=0.00029) and 27% (p=0.00017) increase in the average
      dsDNA content at 4 and 7 days over the sham control group, respectively. Alkaline
      phosphatase activity was significantly increased by the treatment of ultrasound
      at 4 (p=0.012) and 7 days (p=0.035). These results suggested that ultrasound
      treatment with low-intensity acoustic energy facilitated the cellular ingrowth
      and enhanced the proliferation and early differentiation of osteoblasts in SiC
      scaffolds. 

PMID- 24935161
TI  - The effect of specific rhlA-las-box mutations on DNA binding and gene activation
      by Pseudomonas aeruginosa quorum-sensing transcriptional regulators RhlR and
      LasR.
AB  - Pseudomonas aeruginosa is a free-living bacterium and an important opportunistic
      pathogen. The genes coding for virulence-associated traits are regulated at the
      level of transcription by the quorum-sensing response. In this response, the
      regulator LasR coupled with the autoinducer 3-oxo-dodecanoyl homoserine lactone
      (3O-C12-HSL) activates transcription of genes for several virulence factors.
      LasR/3O-C12-HSL also activates transcription of rhlR, the gene coding for the
      transcriptional regulator RhlR, and of rhlI that encodes the synthase that
      produces the autoinducer butanoyl-homoserine lactone (C4-HSL) that interacts with
      RhlR. Genes activated by RhlR/C4-HSL include those involved in rhamnolipids
      production (like the rhlAB operon) and lecA, coding for PA-I lectin. The
      molecular basis of LasR/3O-C12-HSL- and RhlR/C4-HSLDNA-binding specificity (at
      the so-called las-boxes) has not been clearly determined, and the aim of this
      work was to contribute to its understanding. Therefore, we analyzed the
      interaction of LasR and RhlR to variants of the rhlA-las-box that were
      constructed based on the comparison of this las-box to the las-box of lecA. We
      conclude that LasR and RhlR DNA-binding specificity is a complex multifactorial
      phenomenon in which both positive and negative effects are involved and that
      binding of these proteins does not necessarily result in gene activation. 

PMID- 24935160
TI  - Graft surgery in extensive urethral stricture disease.
AB  - Surgical treatment of long urethral stricture disease remains one of the most
      challenging problems in urology. In recent years there has been continuous
      discussion with regard to the etiology, location, length, and management of
      extensive urethral stricture disease. Various tissues such as genital and
      extragenital skin, buccal mucosa, lingual mucosa, small intestinal submucosa, and
      bladder mucosa have been proposed for urethral reconstruction. The most frequent
      questions pertain to the optimal technique for urethroplasty and the optimal
      graft for substitution urethroplasty, as judged by both patient satisfaction and
      outcome success. We review the recent literature with respect to any new
      information on graft urethroplasty for extensive urethral stricture. 

PMID- 24935162
TI  - Pazopanib: a review of its use in the management of advanced renal cell
      carcinoma.
AB  - Pazopanib (Votrient((r))) is an orally administered multi-tyrosine kinase
      inhibitor that is approved in the EU, the US and other countries for the
      treatment of advanced renal cell carcinoma. Pazopanib predominantly inhibits
      vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth
      factor receptor-alpha and -beta, and the stem cell factor receptor c-Kit,
      resulting in inhibition of tumour angiogenesis, cell growth and survival. In
      randomized controlled trials in patients with advanced, predominantly clear-cell,
      renal cell carcinoma, progression-free survival (PFS) and the objective response
      rate were significantly greater in pazopanib recipients than in placebo
      recipients (VEG105192 trial), and pazopanib was noninferior to sunitinib with
      respect to PFS (COMPARZ study). In a patient-preference, crossover study
      involving 10 weeks of treatment with each drug (PISCES study), significantly more
      patients expressed a preference for pazopanib than for sunitinib, with their
      preference being based primarily on tolerability and quality-of-life issues.
      Health-related quality-of-life (HR-QOL) assessments generally favoured pazopanib
      over sunitinib in COMPARZ, and pazopanib did not cause deterioration in HR-QOL
      compared with placebo in VEG105192. Pazopanib caused less myelosuppression, hand
      foot syndrome, mucositis/stomatitis, dysgeusia and fatigue than sunitinib, but
      more abnormal liver function tests. Therefore, pazopanib was noninferior to
      sunitinib with respect to efficacy in the treatment of advanced renal cell
      carcinoma, but had a differentiated tolerability profile, which affected HR-QOL
      and patient preference.

PMID- 24935163
TI  - Fetal and childhood growth patterns associated with bone mass in school-age
      children: the Generation R Study.
AB  - Low birth weight is associated with lower bone accrual in children and peak bone
      mass in adults. We assessed how different patterns of longitudinal fetal and
      early childhood growth influence bone properties at school age. In 5431 children
      participating in a population-based prospective cohort study, we measured fetal
      growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth,
      1, 2, 3, and 4 years of age. We analyzed these growth measurements in relation to
      total body (less head) BMD measured by DXA at age 6. We used conditional growth
      modeling; a technique which takes into account correlation between repeatedly
      measured growth measures. Our results showed that estimated fetal weight gain,
      femur length growth between 20 and 30 weeks of gestation, femur length growth
      between 30 weeks and birth, as well as all height and weight growth measurements
      from birth to 4 years of age were all positively associated with BMC, bone area
      (BA), and BMD (all p < 0.01). Fetal femur length growth between 30 weeks and
      birth was positively associated with BMC and BA (both p < 0.001), but not with
      BMD. Overall, childhood growth measurements exerted a larger influence on bone
      measures than fetal growth measures. The strongest effect estimate was observed
      during the first year of life. Children born small (<10th percentile) for
      gestational age (SGA) had lower BMC and BA, but not BMD, than children born
      appropriate for gestational age (AGA), whereas children born large (>90th
      percentile) for gestational age (LGA) had higher BMC and BA (all p < 0.001).
      These differences were no longer present in children showing subsequent
      accelerated and decelerated infant growth, respectively. We conclude that both
      fetal and childhood growth patterns are associated with bone mineral accrual,
      showing the strongest effect estimates in infancy. Compensatory infant growth
      counteracts the adverse consequences of fetal growth restriction on bone
      development.

PMID- 24935164
TI  - Epidemiology of distal forearm fractures in Austria between 1989 and 2010.
AB  - Only few studies have been published hitherto on country-specific incidence of
      distal forearm fracture. In the prevailing study, incidences were estimated, and
      trend analyses were performed for the entire Austrian population aged >=50a.
      Incidence decreased significantly in women, but not in men, over the past 12
      years of observation. INTRODUCTION: To estimate incidence of distal forearm
      fracture and assess incidence trends in the entire Austrian population aged >=50a
      from 1989-2010 for inpatient fractures and from 1999 to 2010 for all fractures.
      METHODS: The number of inpatient forearm fractures was obtained from the Austrian
      Hospital Discharge Register (AHDR) for the entire population aged >=50a from 1989
      to 2010. Total number of distal forearm fractures was modeled using patient-level
      data on 36,327 patients with distal forearm fractures. Crude and age-standardized
      incidence rates (cases per 100,000) were estimated in 5-year age intervals. To
      analyze the change in incidence over time, average annual changes expressed as
      incidence rate ratios (IRR) were calculated. RESULTS: For all distal forearm
      fractures, age-standardized incidence in women in 1999 and 2009 were estimated at
      709 (95 % CI 675-743) and 607 (578-637), respectively. The age-standardized
      incidences in men the same years were estimated at 171 (156-185) and 162 (151
      174), respectively. IRR analyses showed a significant decrease in women (-1.1 %,
      p < 0.01) but not in men (-0.8 %, p > 0.05) over the last 12 years (1999-2010).
      CONCLUSION: Incidence of distal forearm fracture in the entire Austrian
      population is comparable to hip fracture incidence which is known to be among the
      highest worldwide. However, trend analyses reveal a significant decrease for all
      distal forearm fractures in women, but not in men, over the last 12 years.

PMID- 24935166
TI  - Base mediated 7-exo-dig intramolecular cyclization of Ugi-propargyl precursors: a
      highly efficient and regioselective synthetic approach toward diverse 1,4
      benzoxazepine-5(2H)-ones.
AB  - A metal-free facile and efficient two-step synthetic protocol for the preparation
      of 1,4-benzoxazepine-5(2H)-one derivatives has been developed. The protocol
      involves Ugi reaction followed by K2CO3 mediated highly regioselective 7-exo-dig
      intramolecular cyclization of less-nucleophilic oxygen with the pendant alkyne
      moiety of an Ugi-propargyl precursor to afford the 1,4-benzoxazepine-5(2H)-one
      derivatives in good to excellent yields. 

PMID- 24935165
TI  - Exacerbation of myasthenia gravis by alendronate.
AB  - Myasthenia gravis is an important indication for the long-term prescription of
      corticosteroids. We present a patient with myasthenia gravis who had worsening of
      symptoms associated with the use of alendronate. A 24-year-old patient with
      myasthenia gravis had been administered oral systemic corticosteroid (deflazacort
      40 mg/day) for 3 years in order to control his myasthenic symptoms. One year
      earlier, his lumbar spine bone mineral density was decreased. He was started on
      oral calcium/vitamin D3 and alendronate (70-mg tablets once a week) for
      osteoporosis. He reported an exacerbation of muscle weakness and extreme fatigue
      on days when he took alendronate. He could not work on these days and has to be
      on leave. Alendronate was stopped, and he was started on intravenous ibandronate
      injections given every 3 months. He did not experience muscle weakness and
      fatigue with ibandronate therapy. Alendronate should be used with caution in
      patients with myasthenia gravis who have corticosteroid-induced osteoporosis. 

PMID- 24935167
TI  - The interaction of neutral evolutionary processes with climatically-driven
      adaptive changes in the 3D shape of the human os coxae.
AB  - Differences in the breadth of the pelvis among modern human populations and among
      extinct hominin species have often been interpreted in the light of
      thermoregulatory adaptation, whereby a larger pelvic girdle would help preserve
      body temperature in cold environments while a narrower pelvis would help
      dissipate heat in tropical climates. There is, however, a theoretical problem in
      interpreting a pattern of variation as evidence of selection without first
      accounting for the effects of neutral evolutionary processes (i.e., mutation,
      genetic drift and migration). Here, we analyse 3D configurations of 27 landmarks
      on the os coxae of 1494 modern human individuals representing 30 male and 23
      female populations from five continents and a range of climatic conditions. We
      test for the effects of climate on the size and shape of the pelvic bone, while
      explicitly accounting for population history (i.e., geographically-mediated gene
      flow and genetic drift). We find that neutral processes account for a substantial
      proportion of shape variance in the human os coxae in both sexes. Beyond the
      neutral pattern due to population history, temperature is a significant predictor
      of shape and size variation in the os coxae, at least in males. The effect of
      climate on the shape of the pelvic bone, however, is comparatively limited,
      explaining only a small percentage of shape variation in males and females. In
      accordance with previous hypotheses, the size of the os coxae tends to increase
      with decreasing temperature, although the significance of the association is
      reduced when population history is taken into account. In conclusion, the shape
      and size of the human os coxae reflect both neutral evolutionary processes and
      climatically-driven adaptive changes. Neutral processes have a substantial effect
      on pelvic variation, suggesting such factors will need to be taken into account
      in future studies of human and fossil hominin coxal variation. 

PMID- 24935169
TI  - Studies on a frustrated Heisenberg spin chain with alternating ferromagnetic and
      antiferromagnetic exchanges.
AB  - We study Heisenberg spin-1/2 and spin-1 chains with alternating ferromagnetic
      (J(F)(1)) and antiferromagnetic (J(A)(1)) nearest-neighbor interactions and a
      ferromagnetic next-nearest-neighbor interaction (J(F)(2)). In this model
      frustration is present due to the non-zero J(F)(2). The model with site spin s
      behaves like a Haldane spin chain, with site spin 2s in the limit of vanishing
      J(F)(2)and large J(F)(1)/J(A)(1). We show that the exact ground state of the
      model can be found along a line in the parameter space. For fixed J(F)(1), the
      phase diagram in the space of J(A)(1)-J(F)(2) is determined using numerical
      techniques complemented by analytical calculations. A number of quantities,
      including the structure factor, energy gap, entanglement entropy and zero
      temperature magnetization, are studied to understand the complete phase diagram.
      An interesting and potentially important feature of this model is that it can
      exhibit a macroscopic magnetization jump in the presence of a magnetic field; we
      study this using an effective Hamiltonian.

PMID- 24935168
TI  - Further evidence for phenotypic signatures of hybridization in descendant baboon
      populations.
AB  - Hybridization may have played a substantial role in shaping the diversity of our
      evolving lineage. Although recent genomic evidence has shown that hybridization
      occurred between anatomically modern humans (AMHS) and Neanderthals, it remains
      difficult to pin down precisely where and when this gene flow took place.
      Investigations of the hybrid phenotype in primates and other mammals are
      providing models for identifying signatures of hybridization in the fossil
      record. However, our understanding of intra- and inter-taxon variation in hybrids
      is still limited. Moreover, there is little evidence from these studies that is
      pertinent to the question of how long hybrid skeletal traits persist in
      descendants, and therefore it is not clear whether observed hybrid phenotypes are
      evidence of recent (e.g., F1) or much earlier hybridization events. Here, we
      present an analysis updating a previous study of cranial variation in pedigreed
      olive and yellow baboons and their hybrids. Results suggest that traits
      previously associated with hybrids in baboons and other mammalian species are
      also present in this expanded data set; many of these traits are highly
      heritable, confirming a genetic basis for their variation in this mixed
      population. While F1 animals - and especially F1 males - still have the highest
      number of dental anomalies, these and other atypical traits persist into later
      hybrid generations (such as F2 and B1). Moreover, non-F1 recombinants also show
      extremely rare trait variations, including reduced canines and rotated teeth.
      However, these results must be considered in light of the possibility that some
      founding individuals may have themselves been unrecognized hybrids. Despite this,
      the data are compelling, and indicate once again that further controlled research
      remains to be done on primates and other mammals in order to better understand
      variation in the hybrid phenotype.

PMID- 24935170
TI  - Correlates between kinematics and baropodometric measurements for an integrated
      in-vivo assessment of the segmental foot function in gait.
AB  - Baropodometry and multi-segmental foot kinematics are frequently employed to
      obtain insight into the mechanics of the foot-ground interaction in both basic
      research and clinical settings. However, nothing hitherto has been reported on
      the full integration of kinematics with baropodometric parameters, and only a few
      studies have addressed the association between intersegmental kinematics and
      plantar loading within specific foot regions. The aim of this study was to
      understanding the relationships between foot joint mobility and plantar loading
      by focusing on the correlation between these two measures. An integrated pressure
      force-kinematics system was used to measure plantar pressure and rotations
      between foot segments during the stance phase of walking in 10 healthy subjects.
      An anatomically-based mask was applied to each footprint to obtain six regions
      according to the position of the markers; hence each kinematic segment was paired
      with a corresponding area of the plantar surface. Relationships between segmental
      motion and relevant baropodometric data were explored by means of correlation
      analysis. Negative, weak-to-moderate correlations (R(2)<0.5) were found between
      pressure (mean and peak) and inter-segmental range of motion across all foot
      joints except the Calcaneus-Midfoot. Temporal profiles of sagittal-plane
      kinematics and baropodometric parameters were well correlated, particularly at
      the ankle joint. Larger motion in the foot joints during walking was associated
      with lower plantar pressure in almost all regions. The study helps improve our
      understanding of the relationship between joint mobility and plantar loading in
      the healthy foot and represents a critical preliminary analysis before addressing
      possible clinical applications. 

PMID- 24935171
TI  - Effect of step width manipulation on tibial stress during running.
AB  - Narrow step width has been linked to variables associated with tibial stress
      fracture. The purpose of this study was to evaluate the effect of step width on
      bone stresses using a standardized model of the tibia. 15 runners ran at their
      preferred 5k running velocity in three running conditions, preferred step width
      (PSW) and PSW+/-5% of leg length. 10 successful trials of force and 3-D motion
      data were collected. A combination of inverse dynamics, musculoskeletal modeling
      and beam theory was used to estimate stresses applied to the tibia using subject
      specific anthropometrics and motion data. The tibia was modeled as a hollow
      ellipse. Multivariate analysis revealed that tibial stresses at the distal 1/3 of
      the tibia differed with step width manipulation (p=0.002). Compression on the
      posterior and medial aspect of the tibia was inversely related to step width such
      that as step width increased, compression on the surface of tibia decreased
      (linear trend p=0.036 and 0.003). Similarly, tension on the anterior surface of
      the tibia decreased as step width increased (linear trend p=0.029). Widening step
      width linearly reduced shear stress at all 4 sites (p<0.001 for all). The data
      from this study suggests that stresses experienced by the tibia during running
      were influenced by step width when using a standardized model of the tibia. Wider
      step widths were generally associated with reduced loading of the tibia and may
      benefit runners at risk of or experiencing stress injury at the tibia, especially
      if they present with a crossover running style. 

PMID- 24935172
TI  - The effect of stride length on the dynamics of barefoot and shod running.
AB  - A number of interventions and technique changes have been proposed to attempt to
      improve performance and reduce the number of running related injuries. Running
      shoes, barefoot running and alterations in spatio-temporal parameters (stride
      frequency and stride length) have been associated with significant kinematic and
      kinetic changes, which may have implications for performance and injury
      prevention. However, because footwear interventions have been shown to also
      affect spatio-temporal parameters, there is uncertainty regarding the origin of
      the kinematic and kinetic alterations. Therefore, the purpose of this study was
      to independently evaluate the effects of shoes and changes in stride length on
      lower extremity kinetics. Eleven individuals ran over-ground at stride lengths +/
      5 and 10% of their preferred stride length, in both the barefoot and shod
      condition. Three-dimensional motion capture and force plate data were captured
      synchronously and used to compute lower extremity joint moments. We found a
      significant main effect of stride length on anterior-posterior and vertical GRFs,
      and sagittal plane knee and ankle moments in both barefoot and shod running. When
      subjects ran at identical stride lengths in the barefoot and shod conditions we
      did not observe differences for any of the kinetic variables that were measured.
      These findings suggest that barefoot running triggers a decrease in stride
      length, which could lead to a decrease in GRFs and sagittal plane joint moments.
      When evaluating barefoot running as a potential option to reduce injury, it is
      important to consider the associated change in stride length.

PMID- 24935173
TI  - Usefulness of a ventilation tube as a partial ossicular replacement prosthesis
      (PORP) in ossiculoplasty in patients with chronic otitis media.
AB  - BACKGROUND: The principal objective of ossiculoplasty is to reconstruct the sound
      conducting system in the ear to the best possible degree after the elimination of
      pathological lesions from the middle ear. The ossicular chain is reconstructed
      with the use of the patient's own properly modelled ossicles and synthetic
      prostheses. The objective of the study was to assess the degree of hearing
      improvement after tympanoplasty in patients for whom a ventilation tube was used
      as a partial ossicular replacement prosthesis (PORP). MATERIAL AND METHODS:
      Between 2009 and 2012, 387 patients underwent ear surgery at the
      Otolaryngological Teaching Hospital of the Collegium Medicum at the Jagiellonian
      University of Cracow. We focussed on the patients in whom a vibrating element in
      the form of a properly modelled anvil or a ventilation tube was attached to the
      preserved and normally mobile stapes. RESULTS: A significant hearing improvement
      was observed in patients with type 2 tympanoplasty in the course of chronic
      cholesteatoma otitis media and in patients with simple chronic inflammatory
      process in whom a ventilation tube was used as a PORP in the reconstruction.
      Granulation tissue was determined to be an unfavorable factor in the prognosis of
      hearing improvement following tympanoplasty. CONCLUSIONS: Significant hearing
      improvement was observed after type 2 tympanoplasty in patients with
      cholesteatoma whose ossicular chain was not appreciably damaged. A ventilation
      tube used as a PORP is an effective alternative in the reconstruction of the
      ossicular chain.

PMID- 24935174
TI  - Whole genome gene copy number profiling of gastric cancer identifies PAK1 and
      KRAS gene amplification as therapy targets.
AB  - Gastric cancer is the second leading cause of death from cancer worldwide, with
      an approximately 20% 5-year survival rate. To identify molecular subtypes
      associated with the clinical prognosis, in addition to genetic aberrations for
      potential targeted therapeutics, we conducted a comprehensive whole-genome
      analysis of 131 Chinese gastric cancer tissue specimens using whole-genome array
      comparative genomic hybridization. The analyses revealed gene focal
      amplifications, including CTSB, PRKCI, PAK1, STARD13, KRAS, and ABCC4, in
      addition to ERBB2, FGFR2, and MET. The growth of PAK1-amplified gastric cancer
      cells in vitro and in vivo was inhibited when the corresponding mRNA was knocked
      down. Furthermore, both KRAS amplification and KRAS mutation were identified in
      the gastric cancer specimens. KRAS amplification was associated with worse
      clinical outcomes, and the KRAS gene mutation predicted sensitivity to the MEK1/2
      inhibitor AZD6244 in gastric cancer cell lines. In summary, amplified PAK1, as
      well as KRAS amplification/mutation, may represent unique opportunities for
      developing targeted therapeutics for the treatment of gastric cancer.

PMID- 24935175
TI  - Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.
AB  - Acute post-traumatic ventricular dilation and hydrocephalus are relatively
      frequent consequences of traumatic brain injury (TBI). Several recent studies
      have indicated that high iron levels in brain may relate to hydrocephalus
      development after intracranial hemorrhage. However, the role of iron in the
      development of post-traumatic hydrocephalus is still unclear. This study was to
      determine whether or not iron has a role in hydrocephalus development after TBI.
      TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some
      rats had intraventricular injection of iron. Acute hydrocephalus was measured by
      magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2*
      gradient-echo sequence imaging and brain hemoglobin levels. The effect of
      deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute
      hydrocephalus at 24 h (lateral ventricle volume: 24.1 +/- 3.0 vs. 9.9 +/- 0.2
      mm(3) in sham group). Intraventricular injection of iron also caused
      hydrocephalus (25.7 +/- 3.4 vs. 9.0 +/- 0.6 mm(3) in saline group). Deferoxamine
      treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation.
      In conclusion, iron may contribute to acute hydrocephalus after TBI. 

PMID- 24935176
TI  - The intersection of foregut and bariatric surgeries: treating the whole, not the
      parts.

PMID- 24935177
TI  - The effect of bariatric surgery on gout: a comparative study.
AB  - BACKGROUND: Obesity is a risk factor for the development of gout. An increased
      incidence of early gouty attacks after bariatric surgery has been reported, but
      the data is sparse. The effect of weight loss surgery on the behavior of gout
      beyond the immediate postoperative phase remains unclear. The objective of this
      study was to evaluate the pre- and postoperative frequency and features of gouty
      attacks in bariatric surgery patients. METHODS: Charts were reviewed to identify
      patients who had gout before bariatric surgery. Demographic and gout-related
      parameters were recorded. The comparison group consisted of obese individuals
      with gout who underwent nonbariatric upper abdominal procedures. RESULTS: Ninety
      nine morbidly obese patients who underwent bariatric surgery had gout. The
      comparison group consisted of 56 patients. The incidence of early gouty attack in
      the first month after surgery was significantly higher in the bariatric group
      than the nonbariatric group (17.5% versus 1.8%, P = .003). In the bariatric
      group, 23.8% of patients had at least one gouty attack during the 12-month period
      before surgery, which dropped to 8.0% during postoperative months 1-13 (P =
      .005). There was no significant difference in the number of gouty attacks in the
      comparison group before and after surgery (18.2% versus 11.1%, P = .33). There
      was a significant reduction in uric acid levels 13-months after bariatric surgery
      compared with baseline values (9.1+/-2.0 versus 5.6+/-2.5 mg/dL, P = .007).
      CONCLUSION: The frequency of early postoperative gout attacks after bariatric
      surgery is significantly higher than that of patients undergoing other
      procedures. However, the incidence decreases significantly after the first
      postoperative month up to 1 year.

PMID- 24935178
TI  - Is Glucagon-like peptide-1 for real?

PMID- 24935179
TI  - A novel dedicated endoscopic stent for staple-line leaks after laparoscopic
      sleeve gastrectomy: a case series.
AB  - BACKGROUND: Staple-line leak is the most serious complication of laparoscopic
      sleeve gastrectomy (LSG) occurring in .5-7% of cases. Patients with this
      complication are often managed with an esophageal covered, self-expandable metal
      stent positioned at endoscopy. Unfortunately, migration of these stents has been
      reported in 30-50% of cases. A novel fully-covered, self-expanding metal stent
      (Megastent), specifically designed for post-LSG leaks is now available. The
      objective of this study was to describe the first case series of patients with a
      staple-line leak after LSG who were endoscopically managed with such a novel
      stent. METHODS: Four patients who developed a staple-line leak after LSG were
      treated by positioning a Megastent at endoscopy. The stents were removed after 8
      weeks. RESULTS: A complete leak repair was achieved in all patients. No stent
      migration occurred. Prokinetic therapy was needed to treat vomiting episodes
      during stent presence. At endoscopic evaluation after stent removal, a decubitus
      lesion at the distal part of the duodenal bulb was observed. CONCLUSION: These
      preliminary results would suggest the use of the Megastent as an option for
      stenting of a staple-line leak after LSG. Further studies are still necessary.

PMID- 24935180
TI  - Intussusception after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Jejuno-jejunal (J-J) intussusception is a rare complication after
      Roux-en-Y gastric bypass (RYGB). Prompt diagnosis is critical as it may lead to
      obstruction and bowel necrosis, but clinical presentation is nonspecific. A
      definitive treatment plan has not been established with intussusception after
      RYGB. The aim of our study was to describe clinical presentation and outcomes of
      treatment in patients with intussusception after RYGB. METHODS: Out of 3022
      patients who underwent laparoscopic RYGB between January 2003 and January 2013,
      12 (0.4%) patients presented with intussusception after RYGB. A retrospective
      review of a prospectively collected database was performed. RESULTS: Of the 12
      patients, 11 (91.7%) presented with left or right upper quadrant abdominal pain
      as their chief complaint, and 1 (8.3%) presented with persistent nausea and
      vomiting. Diagnosis was made by computed tomographic scan (n = 1) or
      intraoperative findings (n = 11) at a mean period of 24.9 +/- 26.0 months (range
      3-85) after laparoscopic RYGB. Seven (58.3%) patients were treated only with
      reduction, 2 (16.7%) with resection and revision of J-J anastomosis, the
      remaining 3 (25.0%) underwent imbrication/plication of the J-J anastomosis. Only
      1 (8.3%) patient, who was treated by reduction, returned with subsequent finding
      of recurrent intussusception at 9 months. All patients did well at a mean follow
      up of 12.7 +/- 16.4 months (range 1-47). CONCLUSION: While reduction alone of the
      intussusception is safe and effective, there is a risk of recurrence, and
      imbrication of the J-J anastomosis may be a more effective means of treatment.

PMID- 24935181
TI  - Prospective observational study of emergent endotracheal intubation practice in
      the intensive care unit and emergency department of an Australian regional
      tertiary hospital.
AB  - OBJECTIVE: The present study aimed to describe the characteristics and outcomes
      of intubation occurring in the ICU and ED of an Australian tertiary teaching
      hospital. METHODS: This was a prospective observational study of intubation
      practice across the Geelong Hospital over a 6 month period from 1 August 2012 to
      31 January 2013. Data were entered by the intubating team through an online data
      collection form. RESULTS: There were 119 patients intubated and 134 attempts at
      intubation in the ED and ICU over a 6 month period. The first-pass success rate
      was 104/119 (87.4%), and all but a single patient was intubated by the second
      attempt. Propofol, fentanyl, midazolam and suxamethonium were the most common
      drugs used in rapid sequence induction. AEs were reported in 44/134 (32.8%) of
      intubation attempts, with transient hypoxia and hypotension being the most
      common. A significant adverse outcome, namely aspiration pneumonitis, occurred in
      one patient. There were no peri-intubation deaths. CONCLUSION: The majority of
      airways are managed by ICU and ED consultants and trainees, with success rates
      and AE rates comparable with other published studies.

PMID- 24935182
TI  - Effects of melatonin derivatives on human malaria parasite Plasmodium falciparum.
AB  - Melatonin's function in modulating the circadian cycle of Plasmodium falciparum
      has been an intense investigation for the past 45 years. The stimulatory effects
      of melatonin on malaria growth, development and differentiation have been
      confirmed by numerous studies conducted in the past 40 years but the molecular
      mechanisms underlying melatonin stimulatory effects have been well understood
      recently. Melatonin has been identified as a "signal" essential for
      synchronization of malaria parasitic cell cycle. Melatonin has been shown to
      modulate the release of intracellular Ca2+ and cAMP in Plasmodium falciparum. In
      this context, melatonin receptor blocking agent luzindole has been shown to block
      melatonin's actions in these intracellular events occurring in human malaria
      parasites. Recent studies have resulted in the synthesis and development of
      melatonin derivatives, compounds 7-11 and 12-16. Of these compounds 12, 13 and 14
      were able to inhibit the Plasmodium falciparum growth and this serves as a
      promising lead for the development of future antimalarial compounds that will
      have rapid antimalarial actions with low toxicity. Some antimalarial drugs that
      have been patented are also summarized in this review.

PMID- 24935184
TI  - Retarded hydrodynamic properties of fractal clusters.
AB  - Fractal clusters are commonly encountered when working with the stability and the
      aggregation of colloidal suspensions. In spite of the number of studies that have
      focused on their stationary hydrodynamic properties, no information is currently
      known on their retarded hydrodynamic properties. The objective of this work is to
      close this gap. Clusters with a broad range of fractal dimension values,
      generated via Monte-Carlo simulations have been analyzed. A rigorous model based
      on multipole expansion of time-dependent Stokes equations has been developed, and
      then the full cluster resistance matrix as a function of the frequency has been
      computed. An attempt has been made to extend Basset, Boussinesque and Oseen
      equations to fractal clusters, but it was found that the corresponding
      hydrodynamic radius needs to be a function of frequency. In the case of
      translational motion, the cluster hydrodynamic radius loses any structural
      information at high frequencies, becoming independent of the fractal dimension,
      but depending only on its mass. A simplified model, based on an extension of
      Kirkwood-Rieseman approach has also been developed. This allows one to perform
      calculations for clusters with arbitrary masses and fractal dimensions, with good
      accuracy and very low computational time. It is the first time that the frequency
      dependence of hydrodynamic properties of complex non-spherical objects has been
      investigated. 

PMID- 24935183
TI  - Activity of alkaline phosphatase adsorbed and grafted on "polydopamine" films.
AB  - The oxidation of dopamine in slightly basic solutions and in the presence of
      oxygen as an oxidant allows for the deposition of dopamine-eumelanin
      ("polydopamine") films on almost all kinds of materials allowing for an easy
      secondary functionalization. Molecules carrying nucleophilic groups like thiols
      and amines can be easily grafted on those films. Herein we show that alkaline
      phosphatase (ALP), as a model enzyme, adsorbs to "polydopamine" films and part of
      the adsorbed enzyme is rapidly desorbed in contact with Tris buffer. However a
      significant part of the enzyme remains irreversibly adsorbed and keeps some
      enzymatic activity for at least 2 weeks whereas ALP adsorbed on quartz slides is
      rapidly and quantitatively deactivated. In addition we estimated the Michaelis
      constant Km of the enzyme irreversibly bound to the "polydopamine" film. The
      Michaelis constant, and hence the affinity constant between paranitrophenol
      phosphate and ALP are almost identical between the enzyme bound on the film and
      the free enzyme in solution. Complementarily, it was found that "polydopamine"
      films display some phosphatase like catalytic activity.

PMID- 24935186
TI  - Application of Mn/MCM-41 as an adsorbent to remove methyl blue from aqueous
      solution.
AB  - In this study, the application of Mn loaded MCM-41 (Mn/MCM-41) was reported as a
      novel adsorbent for methyl blue (MB) from aqueous solution. The mesoporous
      structure of Mn/MCM-41 was confirmed by XRD technique. Surface area, pore size
      and wall thickness were calculated from BET equation and BJH method using
      nitrogen sorption technique. FT-IR studies showed that Mn were loaded on the
      hexagonal mesoporous structures of MCM-41. It is found that the MCM-41 structure
      retained after loading of Mn but its surface area and pore diameter decreased due
      to pore blockage. Adsorption of MB from aqueous solution was investigated by
      Mn/MCM-41 with changing Mn content, adsorbent dosage, initial MB concentration,
      contact time, pH and the temperature. Under the chosen condition (25 degrees C,
      0.02 g adsorbent dosage, 6.32 pH, 50 mg L(-1) MB, 1 wt.% Mn), a high MB
      adsorption capacity (45.38 mg g(-1)) was achieved by Mn/MCM-41 process at 120
      min, 8.6 times higher than MCM-41. The electrostatic interaction was considered
      to be the main mechanism for the dye adsorption. The experimental data fitted
      well to Freundlich and Dubinin-Radushkevich isotherms. The adsorption of MB on
      Mn/MCM-41 followed pseudo-second-order kinetics. Thermodynamic parameters
      suggested that the adsorption process is endothermic and spontaneous.

PMID- 24935185
TI  - Nanovesicle formation and microstructure in aqueous
      ditallowethylesterdimethylammonium chloride (DEEDMAC) solutions.
AB  - HYPOTHESIS: Surfactant vesicles composed of ditallowethylesterdimethylammonium
      chloride (DEEDMAC), a cationic double tail surfactant, are commonly present in
      personal care industrial formulations such as fabric softeners. There is
      significant interest in formulating vesicle dispersions, investigation of
      stability, characterization of their structure and flow properties due to the
      biodegradable nature of DEEDMAC. EXPERIMENTS: We investigate the formation and
      structure of unilamellar nanovesicles having a shell made of DEEDMAC and a core
      containing water. We use bright field optical microscopy to elucidate the
      formation mechanism, and a combination of small angle neutron scattering (SANS),
      cryogenic transmission electron microscopy (cryo-TEM), viscometry, densitometry,
      dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and zeta
      potential measurements to determine the nanostructure of well-defined surfactant
      nanovesicles (~15 nm diameter). FINDINGS: We report methods for the determination
      of volume fraction of nanovesicles and vesicle density, which are crucial for
      quantitative estimation of nanovesicle performance in practical applications and
      for predicting vesicle stability. The nanovesicle volume fraction can be obtained
      directly from the intrinsic viscosity and density. The robust method presented
      here is simple and effective as confirmed by quantitative agreement of the
      results with independent SANS measurements.

PMID- 24935188
TI  - Nanoparticle zeta-potential measurements using tunable resistive pulse sensing
      with variable pressure.
AB  - Modern resistive pulse sensing techniques can be used to measure nanoparticle
      electrophoretic mobility, and hence zeta-potential. In contrast to conventional
      light scattering methods, resistive pulse sensing produces particle-by-particle
      data. We have used tunable resistive pulse sensing (TRPS) to compare methods for
      measuring the zeta-potential of carboxylated polystyrene nanoparticles. The five
      particle sets studied had nominal surface charge density (sigma) between 0 and 
      0.67 C m(-2), and diameters in the range 160-230 nm. Data were collected with
      pressure in the range +/-500 Pa applied across a tunable pore. In each
      experiment, pressure was varied either continuously or in discrete steps.
      Calculations of the zeta-potential were obtained by analysing both the rate and
      the full-width half maximum duration of resistive pulses. Data obtained from
      duration analyses were more reproducible than rate methods, yielding typical
      variations smaller than +/-5 mV. When sigma was greater (less negative) than 
      0.32 C m(-2), all of the analysis methods studied yielded a monotonic
      relationship between zeta-potential and sigma. Complicated pulse data were
      observed near the pressure at which the net particle flux is zero, and these
      observations have been explored by examining competition between electrokinetic
      and pressure-driven transport. The typical difference between zeta-potentials
      obtained using TRPS and phase analysis light scattering was 15% (<5 mV), with an
      experimental error of ~10% attributable to both techniques.

PMID- 24935187
TI  - Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer
      microspheres for delivery of anti-cancer drug.
AB  - The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive
      poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine/poly(N-isopropylacrylamide-co
      glycidyl methacrylate-co-N,N-bis(acryloyl)cystamine) microspheres were prepared
      by a two-stage distillation-precipitation polymerization with subsequent surface
      modification with FA. The microspheres were characterized by transmission
      electron microscopy, dynamical light scattering, Fourier-transform infrared
      spectra, UV-vis spectra and elemental analysis. The degradation of the functional
      microspheres could be triggered by a reductive reagent, such as glutathione, due
      to presence of BAC crosslinker. The drug-loaded microspheres exhibited a
      pH/temperature/redox multi-stimuli responsive drug release character for
      doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently
      loaded into the microspheres with a high loading capacity of 208.0% and an
      encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that
      the FA-conjugated microspheres could deliver Dox into MCF-7 cells more
      efficiently than the microspheres without functionalization of FA. Furthermore,
      WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells
      even at a high concentration of 2000 MUg mL(-1). The resultant microsphere may be
      a promising vector for delivery of anti-cancer drugs as it exhibits a low
      cytotoxicity and degradability, precise molecular targeting property and multi
      stimuli responsively controlled drug release.

PMID- 24935189
TI  - Vapor-phase hydrothermal synthesis of rutile TiO2 nanostructured film with
      exposed pyramid-shaped (111) surface and superiorly photoelectrocatalytic
      performance.
AB  - Rutile TiO2 nanostructured film with exposed pyramid-shaped (111) surface was
      successfully fabricated using metal titanium foil as substrate through a facile
      vapor-phase hydrothermal method. The fabricated rutile TiO2 film was composed of
      vertically aligned rod-like structures with diameters ranged from 400 to 700 nm
      and thickness of ca. 2.0 MUm. The obtained rutile TiO2 film as photoanode
      exhibited excellent photoelectrocatalytic activity toward water oxidation and
      rhodamine B decolorization under UV illumination, which was more than 3.5 and 1.2
      times of that obtained by highly ordered anatase TiO2 nanotube array film
      photoanode under the same experimental conditions, respectively. The excellent
      photoelectrocatalytic performance of the rutile TiO2 film photoanode could be due
      to the superior photoelectron transfer property and the high oxidative capability
      of {111} crystal facets. The superior photoelectron transfer capability of the
      photoanodes was manifested by the inherent resistance (R0) of the photoanodes
      using a simple photoelectrochemical method. The calculated R0 values were 50.5
      and 86.2 Omega for the rutile TiO2 nanostructured film and anatase TiO2 nanotube
      array film, respectively. Lower R0 value of the rutile TiO2 photoanode indicated
      a superior photoelectron transfer capability owing to good single crystal
      property of the rod-like rutile nanostructure. Almost identical valence band
      level (1.94 eV) of the rutile TiO2 nanostructured film and anatase TiO2 nanotube
      array film (meaning a similar oxidation capability) further confirmed the
      significant role of photoelectron transfer capability and exposed high-energy
      {111} crystal facets for improved photoelectrocatalytic performance of the rutile
      TiO2 nanostructured film photoanode.

PMID- 24935190
TI  - Synthesis of mesoporous silica hollow nanospheres with multiple gold cores and
      catalytic activity.
AB  - The core-shell Au@resorcinol-formaldehyde (RF) nanospheres with multiple cores
      have been successfully synthesized by a modified Stober method. After coating
      mesoporous silica and the calcination, the Au@meso-SiO2 hollow nanospheres with
      multiple gold cores can be obtained, which have a high surface area (~537 m(2)/g)
      and uniform pore size (~2.5 nm). The Au@meso-SiO2 hollow nanospheres can be used
      as a catalyst for the reduction of 4-nitrophenol by NaBH4 into 4-aminophenol, and
      exhibit excellent catalytic performance.

PMID- 24935191
TI  - Conversion of waste FGD gypsum into hydroxyapatite for removal of Pb2+ and Cd2+
      from wastewater.
AB  - Flue gas desulfurization (FGD) gypsum, a familiar waste generated from coal-fired
      power plants, was successfully transformed to hydroxyapatite (FGD-HAP) by
      hydrothermal method. The obtained FGD-HAP was characterized by XRD, FTIR, TEM and
      BET methods and investigated as adsorbent for removal of Pb(2+) and Cd(2+) from
      wastewater. Batch experiments were performed by varying the pH values, contact
      time and initial metal concentration. The result of pH impact showed that the
      adsorption of two ions was pH dependent process, and the pH 5.0-6.0 was found to
      be the optimum condition. The achieved experimental data were analyzed with
      various kinetic and isotherm models. The kinetic studies displayed that the
      pseudo-second order kinetic model could describe adsorption processes well with
      high correlation coefficient, and the Langmuir isotherm model provided the best
      fit to the equilibrium experimental data. The maximum adsorption capacities
      calculated from Langmuir equation were 277.8 and 43.10mg/g for Pb(2+) and Cd(2+),
      respectively, which can compete with other adsorbents. The thermodynamic
      parameters revealed the adsorption processes were endothermic and spontaneous in
      nature. In binary adsorption, the amount of Cd(2+) adsorbed on FGD-HAP decreased
      by 46.0% with increasing concentration of Pb(2+), which was higher than that of
      Pb(2+)(21.7%), demonstrating the stronger affinity between FGD-HAP and Pb(2+).
      The highest amount of Pb(2+) and Cd(2+) desorbed from saturated FGD-HAP by EDTA
      solution confirmed the FGD-HAP was a promising alternative adsorbent in treatment
      of toxic Pb(2+) and Cd(2+) wastewater.

PMID- 24935192
TI  - Preparation and biological evaluation of photoluminescent carbonaceous
      nanospheres.
AB  - Carbon nanospheres (CNP) possess several unique properties that render CNP
      superior to traditional organic dyes and quantum dots in the biological
      application. However, the interaction of CNP with biological systems was far from
      well-known. In this study, a simple method using cocoon silk was used to
      synthesize photoluminescent CNP. The particle size of CNP was 100.6 nm with well
      dispersity. The excitation/emission wavelength was 340 nm and 442 nm. Cellular
      uptake demonstrated the uptake of CNP by A549 cells was a time-, concentration-
      and energy-dependent procedure. Endosome was involved in the uptake rather than
      mitochondria. Through several uptake inhibitors, it showed the uptake was energy
      dependent and mainly mediated by clathrin-mediated endocytosis. In vivo, CNP were
      mainly distributed in heart and lung, while only a modest amount of CNP was
      distributed in spleen, liver and kidney. The distribution in tumor was relatively
      low, which made CNP a candidate for heart cell imaging. At as high as 2mg/mL, CNP
      showed no obvious toxicity to cells. The hemolysis rate of CNP was also lower
      than 10%. These results suggested CNP was relatively safe in biological
      application.

PMID- 24935193
TI  - Macroporous crosslinked polydivinylbenzene/polyacryldiethylenetriamine
      (PDVB/PADETA) interpenetrating polymer networks (IPNs) and their efficient
      adsorption to o-aminobenzoic acid from aqueous solutions.
AB  - Macroporous crosslinked polydivinylbenzene/polyacryldiethylenetriamine
      (PDVB/PADETA) interpenetrating polymer networks (IPNs) were prepared in this
      study and their adsorption performance was investigated using o-aminobenzoic acid
      as the adsorbate. The results indicated that PDVB/PADETA IPNs had a large
      equilibrium capacity to o-aminobenzoic acid, the Freundlich and Sips models were
      appropriate for fitting the equilibrium data, and the isosteric enthalpy kept
      constant (about -30 kJ mol(-1)) with the equilibrium capacity at 5-125 mg g(-1).
      The pseudo-first-order rate equation characterized the kinetic data better than
      the pseudo-second-order rate equation. At an initial concentration of 593.1 mg L(
      1) and a flow rate of 84 mL h(-1), the breakthrough and saturated capacities were
      50.62 and 95.70 mg mL(-1) wet resin, respectively, and the resin column could be
      regenerated by 0.1 mol L(-1) of sodium hydroxide (w/v) and 40% of ethanol (v/v).

PMID- 24935194
TI  - Cutaneous Richter syndrome: a better place to transform?
AB  - The development of high-grade lymphoma in patients with chronic lymphocytic
      leukaemia is known as Richter syndrome (RS) and is associated with a grave
      prognosis, with a mean survival of 8 months despite treatment. Cutaneous RS has
      been described in a handful of cases and may be associated with a better outcome
      than the more common extracutaneous variants. We review the literature with
      particular emphasis on pathogenesis, treatment and survival of RS. We postulate
      that the absence of B symptoms and a normal lactate dehydrogenase level,
      presumably reflecting localized or limited disease, and a lower tumour burden,
      may explain the apparently better survival in some patients with cutaneous RS
      than with extracutaneous variants. 

PMID- 24935195
TI  - Geographic variation in sex-chromosome differentiation in the common frog (Rana
      temporaria).
AB  - In sharp contrast with birds and mammals, sex-determination systems in
      ectothermic vertebrates are often highly dynamic and sometimes multifactorial.
      Both environmental and genetic effects have been documented in common frogs (Rana
      temporaria). One genetic linkage group, mapping to the largest pair of
      chromosomes and harbouring the candidate sex-determining gene Dmrt1, associates
      with sex in several populations throughout Europe, but association varies both
      within and among populations. Here, we show that sex association at this linkage
      group differs among populations along a 1500-km transect across Sweden. Genetic
      differentiation between sexes is strongest (FST  = 0.152) in a northern-boreal
      population, where male-specific alleles and heterozygote excesses (FIS  = -0.418
      in males, +0.025 in females) testify to a male-heterogametic system and lack of X
      Y recombination. In the southernmost population (nemoral climate), in contrast,
      sexes share the same alleles at the same frequencies (FST  = 0.007 between
      sexes), suggesting unrestricted recombination. Other populations show
      intermediate levels of sex differentiation, with males falling in two categories:
      some cluster with females, while others display male-specific Y haplotypes. This
      polymorphism may result from differences between populations in the patterns of X
      Y recombination, co-option of an alternative sex-chromosome pair, or a mixed sex
      determination system where maleness is controlled either by genes or by
      environment depending on populations or families. We propose approaches to test
      among these alternative models, to disentangle the effects of climate and
      phylogeography on the latitudinal trend, and to sort out how this polymorphism
      relates to the 'sexual races' described in common frogs in the 1930s. 

PMID- 24935197
TI  - The risk of switch to mania in patients with bipolar disorder during treatment
      with an antidepressant alone and in combination with a mood stabilizer.
AB  - OBJECTIVE: This study examined the risk of antidepressant-induced manic switch in
      patients with bipolar disorder treated either with antidepressant monotherapy or
      with an antidepressant in conjunction with a mood stabilizer. METHOD: Using
      Swedish national registries, the authors identified 3,240 patients with bipolar
      disorder who started treatment with an antidepressant and had no antidepressant
      treatment during the previous year. Patients were categorized into those
      receiving antidepressant monotherapy and those receiving an antidepressant plus a
      mood stabilizer. A within-individual design was used to control for confounding
      by disorder severity, genetic makeup, and early environmental factors. Cox
      regression analyses conditioned on individual were used to compare the rate of
      mania 0-3 months and 3-9 months after the start of antidepressant treatment with
      a preceding non-treatment period. RESULTS: Nearly 35% of the patients were
      treated with antidepressant monotherapy. The increased risk of treatment-emergent
      mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83,
      95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no
      acute change in risk of mania was observed during the 3 months after the start of
      antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased
      risk was observed during the period 3-9 months after treatment initiation (hazard
      ratio=0.63, 95% CI=0.42, 0.93). CONCLUSIONS: In this national registry study,
      antidepressant monotherapy was associated with an increased risk of mania.
      However, no risk of mania was seen in patients receiving an antidepressant while
      treated with a mood stabilizer. The results highlight the importance of avoiding
      antidepressant monotherapy in the treatment of bipolar disorder.

PMID- 24935196
TI  - DAP12 deficiency in liver allografts results in enhanced donor DC migration,
      augmented effector T cell responses and abrogation of transplant tolerance.
AB  - Liver interstitial dendritic cells (DC) have been implicated in immune regulation
      and tolerance induction. We found that the transmembrane immuno-adaptor DNAX
      activating protein of 12 kDa (DAP12) negatively regulated conventional liver
      myeloid (m) DC maturation and their in vivo migratory and T cell allostimulatory
      ability. Livers were transplanted from C57BL/6(H2(b) ) (B6) WT or DAP12(-/-) mice
      into WT C3H (H2(k) ) recipients. Donor mDC (H2-K(b+) CD11c(+) ) were quantified
      in spleens by flow cytometry. Anti-donor T cell reactivity was evaluated by ex
      vivo carboxyfluorescein diacetate succinimidyl ester-mixed leukocyte reaction and
      delayed-type hypersensitivity responses, while T effector and regulatory T cells
      were determined by flow analysis. A threefold to fourfold increase in donor
      derived DC was detected in spleens of DAP12(-/-) liver recipients compared with
      those given WT grafts. Moreover, pro-inflammatory cytokine gene expression in the
      graft, interferon gamma (IFNgamma) production by graft-infiltrating CD8(+) T
      cells and systemic levels of IFNgamma were all elevated significantly in DAP12(-/
      ) liver recipients. DAP12(-/-) grafts also exhibited reduced incidences of CD4(+)
      Foxp3(+) cells and enhanced CD8(+) T cell IFNgamma secretion in response to donor
      antigen challenge. Unlike WT grafts, DAP12(-/-) livers failed to induce tolerance
      and were rejected acutely. Thus, DAP12 expression in liver grafts regulates donor
      mDC migration to host lymphoid tissue, alloreactive T cell responses and
      transplant tolerance. 

PMID- 24935198
TI  - Hydrodynamic slip on DNA observed by optical tweezers-controlled translocation
      experiments with solid-state and lipid-coated nanopores.
AB  - We use optical tweezers to investigate the threading force on a single dsDNA
      molecule inside silicon-nitride nanopores between 6 and 70 nm in diameter, as
      well as lipid-coated solid-state nanopores. We observe a strong increase of the
      threading force for decreasing nanopore size that can be attributed to a
      significant reduction in the electroosmotic flow (EOF), which opposes the
      electrophoresis. Additionally, we show that the EOF can also be reduced by
      coating the nanopore wall with an electrically neutral lipid bilayer, resulting
      in an 85% increase in threading force. All experimental findings can be described
      by a quantitative theoretical model that incorporates a hydrodynamic slip effect
      on the DNA surface with a slip length of 0.5 nm. 

PMID- 24935199
TI  - Probe-based confocal laser endomicroscopy and fluorescence-based enhanced reality
      for real-time assessment of intestinal microcirculation in a porcine model of
      sigmoid ischemia.
AB  - BACKGROUND AND AIM: Surgeons currently rely on visual clues to estimate the
      presence of sufficient vascularity for safe anastomosis. We aimed to assess the
      accuracy of endoluminal confocal laser endomicroscopy (CLE) and laparoscopic
      fluorescence-based enhanced reality (FLER), using near-infrared imaging and
      fluorescence from injected Indocyanine Green, to identify the transition from
      ischemic to vascular areas in a porcine model of mesenteric ischemia. METHODS:
      Six pigs underwent 1-h sigmoid segmental ischemia. The ischemic area was
      evaluated by clinical assessment and FLER to determine presumed viable margins.
      For each sigmoid colon, 5 regions of interest (ROIs) were identified: ischemic
      (ROI 1), presumed viable margins ROI 2a (distal) and 2b (proximal), and vascular
      areas 3a (distal) and 3b (proximal). After injection of fluorescein, CLE scanning
      of the mucosa from the ischemic area toward viable margins was performed.
      Capillary blood samples were obtained by puncturing the serosa at the ROIs, and
      capillary lactates were measured with the EDGE((r)) analyzer. RESULTS: Capillary
      lactates were significantly higher at ROI 1 (4.91 mmol/L) when compared to
      resection margins (2.8 mmol/L; mean difference: 2.11; p < 0.05) identified by
      FLER. There was no significant difference in lactates between ROI1 and resection
      margins identified by clinical evaluation. In 50 % of cases, ROI 2aCLINIC
      2bCLINIC were considered to match (<1 cm distance) with ROI 2aFLER-2bFLER.
      Confocal analysis revealed specific clues to identify the transition from
      ischemic to viable areas corresponding to those assessed by FLER in 11/12 cases
      versus 7/12 for those identified by clinical evaluation. CONCLUSIONS: In this
      experimental model, FLER and CLE were more accurate than clinical evaluation to
      delineate bowel vascularization.

PMID- 24935200
TI  - The impact of laparoscopic anti-reflux surgery in patients with Barrett's
      esophagus.
AB  - BACKGROUND: Barrett's esophagus (BE) is a major risk factor for esophageal
      adenocarcinoma. It is believed that BE is caused by chronic gastro-esophageal
      reflux disease (GERD). Laparoscopic anti-reflux surgery (LARS) restores the
      competency of the cardia and may thereby change the natural course of BE. We
      studied the impact of LARS on the histological profile of BE and on the control
      of GERD. METHODS: We identified all patients with BE who underwent LARS from 1994
      to 2007 and contacted them to assess post-operative GERD symptoms via
      questionnaire. Endoscopy findings, histology, 24 hour pH monitoring, and
      manometry were also collected using our prospectively maintained database.
      Histological regression was defined as either loss of dysplasia or disappearance
      of BE. RESULTS: Two hundred and fifteen patients met the initial inclusion
      criteria; in 82 of them histology from post-operative endoscopy was available for
      review. Endoscopy was performed a median of 8 years (range, 1-16 years) after
      surgery. Regression of BE occurred in 18 (22%) patients while in 6 (7%) BE
      progressed to dysplasia or cancer. Thirty-six (43%) patients underwent pre- and
      post-operative manometry. The median lower esophageal sphincter pressure
      increased from 9 to 17 mmHg in these patients. Thirty-four (41%) patients
      underwent pre- and post-operative pH studies. The median DeMeester score
      decreased from 54 to 9. Sixty-seven (82%) of 82 patients completed the post
      operative questionnaire; 86% of these patients reported improvement in heartburn
      and regurgitation. CONCLUSIONS: LARS was associated with both physiologic and
      symptomatic control of GERD in patients with BE. LARS resulted in regression of
      BE in 22% of patients and progression in 7%. Thus, continued surveillance of
      Barrett's is needed after LARS.

PMID- 24935201
TI  - Hospital-acquired conditions after bariatric surgery: we can predict, but can we
      prevent?
AB  - BACKGROUND: Centers for Medicare and Medicaid Services initiated a non-payment
      policy for certain hospital-acquired conditions (HACs) in 2008. This study aimed
      to determine the rate of the three most common HACs (surgical site infection
      (SSI), urinary tract infection (UTI), and venous thromboembolism (VTE)) among
      bariatric surgery patients. Additionally, the association of HACs with patient
      factors and the effect of HACs on post-operative outcomes were investigated.
      METHODS: Patients over 18 years with a body mass index (BMI) >= 35 who underwent
      bariatric surgery were identified using the American College of Surgeons'
      National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2012).
      Patients were grouped into two categories: HAC versus no HAC patients and
      baseline characteristics and outcomes, including 30-day mortality, reoperation,
      and mean length of stay (LOS) were compared. Multivariable logistic regression
      analysis was performed to identify the risk factors for developing a HAC.
      RESULTS: 98,553 patients were identified, 2,809 (2.9%) developed at least one
      HACs. SSI was the most common HAC (1.8%), followed by UTI (0.7%) and VTE (0.4%).
      The rate of these HACs significantly decreased from 4.6% in 2005-2006 to 2.5% in
      2012 (p < 0.001). Laparoscopic gastric banding was associated with the lowest
      rates of HAC (1.3%) and open gastric bypass with the highest (8.0%). HAC patients
      had significantly higher rates of in-hospital mortality (0.8 vs. 0.1%, p < 0.001)
      and LOS (3.9 vs. 2.1 days, p < 0.001). On adjusted analysis, open GBP patients
      had 5.36-fold higher odds of developing a HAC. Interestingly, the presence of a
      resident surgeon 7-11 years post graduation was associated with significantly
      increased odds of HACs (1.86, 1.50-2.31, p < 0.001). CONCLUSION: Our data
      demonstrate a strong correlation between these three HACs following bariatric
      surgery and factors intrinsic to the bariatric patient population. This calls
      into question the non-payment policy for inherent patient factors on which they
      cannot have impact. These findings are important to help inform health care
      policy decisions regarding access to care for bariatric surgery patients.

PMID- 24935202
TI  - A multi-center study of using carbon nanoparticles to track lymph node metastasis
      in T1-2 colorectal cancer.
AB  - BACKGROUND: How to identify whether T1-2 colorectal cancers have lymph nodes
      metastases pre-op or intra-op is a crucial problem in clinic. The purpose of this
      study was to evaluate the feasibility of using carbon nanoparticles to track
      lymph nodes metastases in T1-2 colorectal cancers. METHODS: A multi-center study
      was performed between July 2012 and January 2014. Seventy-three patients with T1
      2 colorectal cancer identified by pre-op endoscopic ultrasonography (EUS) were
      recruited. 1 ml carbon nanoparticles suspension was endoscopically injected into
      the submucosal layer at four points around the site of the primary tumor 1 day
      before surgery. Laparoscopic radical resection with lymphadenectomy was
      performed. Sentinel lymph nodes (SLNs) were defined as nodes that were black-dyed
      by carbon nanoparticles. Pathology confirmed whether lymph nodes have cancer
      metastases and the SLNs accuracy. RESULTS: SLNs were easily found under
      laparoscopy. The mean number of SLNs was 3 (range 1-5). All patients had SLNs
      lying alongside the mesenteric vessel or main arterial vessel. After pathological
      analysis, 2 patients (9.52%) had lymph node metastasis in 21 patients with EUS T1
      cancers, and 10 patients (19.23%) had lymph node metastasis in 52 patients with
      EUS T2 cancers. In two T1 cases with lymph node metastasis, SLNs were positive
      with 100% accuracy. In ten T2 cases with lymph node metastasis, SLNs were
      positive in nine cases. In pathology, carbon nanoparticles were seen in lymphatic
      vessels, and lymphoid sinus and macrophages in negative SLNs. When SLNs were
      positive, carbon nanoparticles were seen around cancer cells in lymph nodes. The
      overall sensitivity, specificity, accuracy of SLNs in T1-2 colorectal cancers
      were 91.67, 100, 98.63%, respectively. CONCLUSIONS: We demonstrated the
      feasibility of using carbon nanoparticles to track lymph nodes metastases in T1-2
      colorectal cancers. Carbon nanoparticles black-dyed lymph nodes play a role as
      SLNs in T1-2 colorectal cancers.

PMID- 24935203
TI  - Efficacy and survival analysis of percutaneous radiofrequency versus microwave
      ablation for hepatocellular carcinoma: an Egyptian multidisciplinary clinic
      experience.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver with
      poor prognosis. For early stage HCC, treatment options include surgical
      resection, liver transplantation, and percutaneous ablation. Percutaneous
      ablative techniques (radiofrequency and microwave techniques) emerged as best
      therapeutic options for nonsurgical patients. AIMS: We aimed to determine the
      safety and efficacy of radiofrequency and microwave procedures for ablation of
      early stage HCC lesions and prospectively follow up our patients for survival
      analysis. PATIENTS AND METHODS: One Hundred and 11 patients with early HCC are
      managed in our multidisciplinary clinic using either radiofrequency or microwave
      ablation. Patients are assessed for efficacy and safety. Complete ablation rate,
      local recurrence, and overall survival analysis are compared between both
      procedures. RESULTS: Radiofrequency ablation group (n = 45) and microwave
      ablation group (n = 66) were nearly comparable as regards the tumor and patients
      characteristics. Complete ablation was achieved in 94.2 and 96.1% of patients
      managed by radiofrequency and microwave ablation techniques, respectively (p
      value 0.6) with a low rate of minor complications (11.1 and 3.2, respectively)
      including subcapsular hematoma, thigh burn, abdominal wall skin burn, and pleural
      effusion. Ablation rates did not differ between ablated lesions <= 3 and 3-5 cm.
      A lower incidence of local recurrence was observed in microwave group (3.9 vs.
      13.5% in radiofrequency group, p value 0.04). No difference between both groups
      as regards de novo lesions, portal vein thrombosis, and abdominal
      lymphadenopathy. The overall actuarial probability of survival was 91.6% at 1
      year and 86.1% at 2 years with a higher survival rates noticed in microwave group
      but still without significant difference (p value 0.49). CONCLUSION:
      Radiofrequency and microwave ablations led to safe and equivalent ablation and
      survival rates (with superiority for microwave ablation as regards the incidence
      of local recurrence).

PMID- 24935204
TI  - Per-oral endoscopic myotomy white paper summary.

PMID- 24935205
TI  - Severe radiotoxicity in an allogeneic transplant recipient with a heterozygous
      ATM mutation.
AB  - Patients receiving radiotherapy often experience toxicity of the skin and mucous
      membranes. While radiotherapy is a mainstay of myeloablative conditioning for
      allogeneic hematopoietic stem cell transplantation (ASCT), no risk factors for
      radiotoxicity have been identified in this setting. Here, we report on a patient
      with excessive radiation-induced toxicity after ASCT who carried a heterozygous
      mutation in the Ataxia telangiectasia mutated (ATM) gene. This is the first case
      to suggest a genetic basis for increased radiotoxicity after myeloablative ASCT. 

PMID- 24935207
TI  - Detection and characterization of emerging psychoactive substances by ion
      mobility spectrometry.
AB  - Rapid detection and identification of novel psychoactive substances (NPS)
      continues to present significant analytical challenges to forensic and analytical
      chemists. Ion mobility spectrometry (IMS) has been traditionally considered as
      the analytical technique of choice to detect illicit drugs in security points in
      airports, borderlines and customs. Databases of the reduced mobility (K0 ) values
      of illicit drugs are available in the scientific literature and they should be
      completed with data of emerging designer drugs. In this paper, we have evaluated
      the effect of different measurement conditions and determined the K0 values of an
      important number of NPS including different families; such as phenethylamines,
      cathinones, synthetic cannabinoids and tryptamines among others to be
      incorporated to the existing data to provide a rapid detection and identification
      of this emerging threat.

PMID- 24935206
TI  - Design and evaluation of locked nucleic acid-based splice-switching
      oligonucleotides in vitro.
AB  - Antisense-mediated modulation of pre-mRNA splicing is an attractive therapeutic
      strategy for genetic diseases. Currently, there are few examples of modulation of
      pre-mRNA splicing using locked nucleic acid (LNA) antisense oligonucleotides,
      and, in particular, no systematic study has addressed the optimal design of LNA
      based splice-switching oligonucleotides (LNA SSOs). Here, we designed a series of
      LNA SSOs complementary to the human dystrophin exon 58 sequence and evaluated
      their ability to induce exon skipping in vitro using reverse transcription
      polymerase chain reaction. We demonstrated that the number of LNAs in the SSO
      sequence and the melting temperature of the SSOs play important roles in inducing
      exon skipping and seem to be key factors for designing efficient LNA SSOs. LNA
      SSO length was an important determinant of activity: a 13-mer with six LNA
      modifications had the highest efficacy, and a 7-mer was the minimal length
      required to induce exon skipping. Evaluation of exon skipping activity using
      mismatched LNA/DNA mixmers revealed that 9-mer LNA SSO allowed a better mismatch
      discrimination. LNA SSOs also induced exon skipping of endogenous human
      dystrophin in primary human skeletal muscle cells. Taken together, our findings
      indicate that LNA SSOs are powerful tools for modulating pre-mRNA splicing. 

PMID- 24935208
TI  - Multiple roles of complement MASP-1 at the interface of innate immune response
      and coagulation.
AB  - MASP-1 is a versatile serine protease that cleaves a number of substrates in
      human blood. In recent years it became evident that besides playing a crucial
      role in complement activation MASP-1 also triggers other cascade systems and even
      cells to mount a more powerful innate immune response. In this review we
      summarize the latest discoveries about the diverse functions of this multi
      faceted protease. Recent studies revealed that among MBL-associated serine
      proteases, MASP-1 is the one responsible for triggering the lectin pathway via
      its ability to rapidly autoactivate then cleave MASP-2, and possibly MASP-3. The
      crystal structure of MASP-1 explains its more relaxed substrate specificity
      compared to the related complement enzymes. Due to the relaxed specificity, MASP
      1 interacts with the coagulation cascade and the kinin generating system, and it
      can also activate endothelial cells eliciting pro-inflammatory signaling. 

PMID- 24935210
TI  - RANZCR Body Systems Framework of diagnostic imaging examination descriptors.
AB  - INTRODUCTION: A unified and logical system of descriptors for diagnostic imaging
      examinations and procedures is a desirable resource for radiology in Australia
      and New Zealand and is needed to support core activities of RANZCR. Existing
      descriptor systems available in Australia and New Zealand (including the Medicare
      DIST and the ACC Schedule) have significant limitations and are inappropriate for
      broader clinical application. METHODS: An anatomically based grid was
      constructed, with anatomical structures arranged in rows and diagnostic imaging
      modalities arranged in columns (including nuclear medicine and positron emission
      tomography). The grid was segregated into five body systems. The cells at the
      intersection of an anatomical structure row and an imaging modality column were
      populated with short, formulaic descriptors of the applicable diagnostic imaging
      examinations. Clinically illogical or physically impossible combinations were
      'greyed out'. Where the same examination applied to different anatomical
      structures, the descriptor was kept identical for the purposes of streamlining.
      RESULTS: The resulting Body Systems Framework of diagnostic imaging examination
      descriptors lists all the reasonably common diagnostic imaging examinations
      currently performed in Australia and New Zealand using a unified grid structure
      allowing navigation by both referrers and radiologists. The Framework has been
      placed on the RANZCR website and is available for access free of charge by
      registered users. CONCLUSION: The Body Systems Framework of diagnostic imaging
      examination descriptors is a system of descriptors based on relationships between
      anatomical structures and imaging modalities. The Framework is now available as a
      resource and reference point for the radiology profession and to support core
      College activities.

PMID- 24935209
TI  - Systolic blood pressure levels among adults with hypertension and incident
      cardiovascular events: the atherosclerosis risk in communities study.
AB  - IMPORTANCE: Studies document a progressive increase in heart disease risk as
      systolic blood pressure (SBP) rises above 115 mm Hg, but it is unknown whether an
      SBP lower than 120 mm Hg among adults with hypertension (HTN) lowers heart
      failure, stroke, and myocardial infarction risk. OBJECTIVE: To examine the risk
      of incident cardiovascular (CV) events among adults with HTN according to 3 SBP
      levels: 140 mm Hg or higher; 120 to 139 mm Hg; and a reference level of lower
      than 120 mm Hg. DESIGN, SETTING, AND PARTICIPANTS: A total of 4480 participants
      with HTN but without prevalent CV disease at baseline (years 1987-1989) from the
      Atherosclerosis Risk in Communities Study were included. Measurements of SBP were
      taken at baseline and at 3 triennial visits; SBP was treated as a time-dependent
      variable and categorized as elevated (>=140 mm Hg), standard (120-139 mm Hg), and
      low (<120 mm Hg). Multivariable Cox regression models included baseline age, sex,
      diabetes status, BMI, high cholesterol level, smoking status, and alcohol intake.
      MAIN OUTCOMES AND MEASURES: Incident composite CV events (heart failure, ischemic
      stroke, myocardial infarction, or death related to coronary heart disease).
      RESULTS: After a median follow-up of 21.8 years, a total of 1622 incident CV
      events had occurred. Participants with elevated SBP developed incident CV events
      at a significantly higher rate than those in the low BP group (adjusted hazard
      ratio [HR], 1.46; 95% CI, 1.26-1.69). However, there was no difference in
      incident CV event-free survival among those in the standard vs low SBP group
      (adjusted HR, 1.00; 95% CI, 0.85-1.17). Further adjustment for BP medication use
      or diastolic BP did not significantly affect the results. CONCLUSIONS AND
      RELEVANCE: Among patients with HTN, having an elevated SBP carries the highest
      risk for cardiovascular events, but in this categorical analysis, once SBP was
      below 140 mm Hg, an SBP lower than 120 mm Hg did not appear to lessen the risk of
      incident CV events.

PMID- 24935211
TI  - Fluid intake from beverages across age groups: a systematic review.
AB  - BACKGROUND: Fluid intake, especially water, is essential for human life and also
      necessary for physical and mental function. The present study aimed to assess
      beverage consumption across age groups. METHODS: A systematic review was
      conducted. Original research in English language publications and available
      studies (or abstracts in English) from 2000 to 2013 was searched for by using the
      medical subheading (MeSH) terms: ('beverage' OR 'fluid' [Major]) AND
      ('consumption' [Mesh] OR 'drinking' [Mesh] OR 'intake' [Mesh]) AND ('child'
      [Mesh] OR 'adolescent' [Mesh] OR 'adult' [Mesh]). Article selection was
      restricted to those papers covering healthy populations of all age groups in a
      nationwide sample, or from a representative sample of the population of a city or
      cities, which examined the trends or patterns of beverage intake and the
      determinants of beverage intake. Sixty-five studies were identified with respect
      to beverage consumption across age groups. The papers were screened by thoroughly
      reading titles or abstracts. Full-text articles were assessed by three
      investigators. RESULTS: Total beverage intake varied between 0.6 and 3.5 L day(
      1) among all age groups (males more than females). Plain water contributed up to
      58%, 75% and 80% of the total beverage intake in children, adolescents and
      adults, respectively. Milk consumption was higher among children; consumption of
      soft drinks was higher among adolescents; and the consumption of tea, coffee and
      alcoholic beverages was higher among adults. CONCLUSIONS: Plain water is the main
      water source for all age groups and the consumption of other beverages varies
      according to age.

PMID- 24935212
TI  - Development of a pseudo/anonymised primary care research database: Proof-of
      concept study.
AB  - General practice records present a comprehensive source of data that could form a
      variety of anonymised or pseudonymised research databases to aid identification
      of potential research participants regardless of location. A proof-of-concept
      study was undertaken to extract data from general practice systems in 15
      practices across the region to form pseudo and anonymised research data sets. Two
      feasibility studies and a disease surveillance study compared numbers of
      potential study participants and accuracy of disease prevalence, respectively.
      There was a marked reduction in screening time and increase in numbers of
      potential study participants identified with the research repository compared
      with conventional methods. Accurate disease prevalence was established and
      enhanced with the addition of selective text mining. This study confirms the
      potential for development of national anonymised research database from general
      practice records in addition to improving data collection for local or national
      audits and epidemiological projects.

PMID- 24935213
TI  - Digital divide and information needs for improving family support among the poor
      and underserved.
AB  - Despite of its emotional benefits, communication with family members who live
      abroad can present a large financial burden for low-income foreign-born
      individuals. The aims of this study were (1) to explore the current technologies
      available for low-cost communication with family living abroad and (2) to assess
      the level of awareness and use of low-cost technologies for family communication
      as well as related information needs among low-income foreign-born individuals.
      This mixed-methods study included an environmental scan, survey, and focus groups
      with low-income foreign-born individuals living in East Harlem in New York City.
      Low-income individuals who have family members living abroad face financial
      stress with complicated technology choices for communication with family living
      abroad and they have many information needs. They would welcome interactive and
      convenient educational tools that (1) build skills for utilization of various
      technologies and (2) provide decision support to simplify choosing among the vast
      array of available communication options. 

PMID- 24935214
TI  - Human type 5 adenovirus-based tuberculosis vaccine: is the respiratory route of
      delivery the future?
AB  - Despite progress in managing TB, there were 8.6 million new cases in 2012. To
      control TB will require a more effective vaccine than BCG, new drugs and better
      diagnostic tests. Recombinant replication-defective adenoviruses expressing
      foreign DNA have been studied as vaccines. We developed and evaluated a
      recombinant replication-deficient human Ad5 vector expressing Ag85A (Ad5Ag85A) as
      a TB vaccine in animal models and a Phase I human study. Animal models of
      Ad5Ag85A show markedly improved protection over BCG alone and immunization via
      the respiratory route provides the best type of protection. In humans,
      intramuscular vaccination was safe; Ad5Ag85A was immunogenic and stimulated
      polyfunctional T cell responses, more potently in previously BCG-vaccinated
      volunteers. Pre-existing Ad5 antibodies did not dampen the response. Given its
      potency, Ad5-based TB vaccines are well-positioned to be delivered to the
      respiratory tract, induce local lung immunity to control TB, and inform
      innovative approaches to new TB vaccination strategies. 

PMID- 24935215
TI  - A new Cretaceous genus of xyelydid sawfly illuminating nygmata evolution in
      Hymenoptera.
AB  - BACKGROUND: Nygmata are prominent glandular structures on the wings of insects.
      They have been documented in some extant insects, including several families of
      Neuroptera and Mecoptera, the majority of Trichoptera, and a few of the
      hymenopteran Symphyta. However, because nygmata are rarely preserved in
      compression fossils, their early development and evolution are still enigmatic.
      For example, the only documented nygmata in the Hymenoptera are on the forewings
      of the Triassic xyelids Asioxyela paurura and Madygenius primitives. RESULTS:
      This study describes and illustrates a new genus and species from the family
      Xyelydidae, Rectilyda sticta gen. et sp. nov., from the Early Cretaceous Yixian
      Formation of Duolun County, Inner Mongolia, China. This genus has 1-RS reclival
      and linearly aligned with 1-M, which is different from all other genera in the
      Xyelydidae. In addition, R. sticta gen. et sp. nov. has clearly preserved
      nygmata: four symmetrical nygmata on each forewing and two on each hind wing.
      CONCLUSION: Previous reports of nygmata on the forewings of Triassic xyelids and
      extant sawflies, together with this new fossil record of nygmata, provide rare
      insights into their developmental trends, as well as into the evolution of
      hymenopterans and insects in general.

PMID- 24935216
TI  - Stereotactic body radiotherapy for very elderly patients (age, greater than or
      equal to 85 years) with stage I non-small cell lung cancer.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) for non-small cell lung cancer
      (NSCLC) is primarily a treatment option for medically inoperable patients, who
      are often elderly. However, few studies report the effects of SBRT in elderly
      patients. Thus, we retrospectively analyzed clinical outcomes and feasibility
      following treatment of very elderly patients (age >= 85 years) with stage Iota
      NSCLC and younger patients (age < 85 years) with SBRT in our institution.
      METHODS: From January 2006 to December 2012, 81 patients (20 very elderly; median
      age, 80 years; age range 64-93 years) with stage Iota NSCLC received SBRT.
      Prescription doses of 48 Gy were delivered in 4 fractions over 2 weeks or doses
      of 60 Gy were delivered in 10 fractions over 3 weeks. RESULTS: Local control was
      achieved in 91.8% of all patients at 3 years (83.1% and 93.8% of very elderly and
      younger patients, respectively), and the 3-year overall survival (OS) rate was
      69.4% (40.7% and 75.0% of very elderly and younger patients, respectively). OS
      rates were significantly shorter for the very elderly group than for the younger
      group, with a 3-year cause-specific survival (CSS) rate of 77.9% (50.4% and 81.6%
      of very elderly and younger patients, respectively) and a 3-year progression-free
      survival (PFS) rate of 59.5% (44.7% and 63.5% in very elderly and younger groups,
      respectively). Multivariate analysis revealed a significant correlation between T
      stage and OS. Grades 2 and 3 radiation pneumonitis (RP) occurred in 7 (8.6%) and
      2 (2.5%) patients, respectively. Among patients of very elderly and younger
      groups, grade 2 RP occurred in 4 (20%) and 3 (4.9%) patients, and grade 3
      occurred in 2 (10%) and 0 (0%) patients, respectively. No grade 4 or 5 toxicity
      was observed, RP was significantly more severe among very elderly patients.
      CONCLUSIONS: SBRT for stage Iota NSCLC was well tolerated and feasible in very
      elderly patients. The efficacy of SBRT was comparable to that achieved in younger
      patients, although very elderly patients experienced significantly more severe
      RP. Although this study cohort included only 20 very elderly patients, the
      present data suggest that decreasing volumes of normal lung tissues exposed to >=
      20 Gy and mean lung doses reduces the risk of RP in very elderly patients. The
      present data warrant studies of larger very elderly cohorts.

PMID- 24935217
TI  - Abnormal aortic arch morphology in Turner syndrome patients is a risk factor for
      hypertension.
AB  - Hypertension in Turner syndrome (TS) is a multifactorial, highly prevalent and
      significant problem that warrants timely diagnosis and rigorous treatment. The
      objective of this study was to investigate the association between abnormal
      aortic arch morphology and hypertension in adult TS patients. This was a single
      centre retrospective study in 74 adult TS patients (age 29.41 +/- 8.91 years) who
      underwent a routine cardiac MRI. Patients were assigned to the hypertensive group
      (N = 31) if blood pressure exceeded 140/90 mmHg and/or if they were treated with
      antihypertensive medication. Aortic arch morphology was evaluated on MRI images
      and initially assigned as normal (N = 54) or abnormal (N = 20), based on the
      curve of the transverse arch and the distance between the left common carotid
      left subclavian artery. We additionally used a new more objective method to
      describe aortic arch abnormality in TS by determination of the relative position
      of the highest point of the transverse arch (AoHP). Logistic regression analysis
      showed that hypertension is significantly and independently associated with age,
      BMI and abnormal arch morphology, with a larger effect size for the new AoHP
      method than for the classical method. TS patients with hypertension and abnormal
      arch morphology more often had dilatation of the ascending aorta. There is a
      significant association between abnormal arch morphology and hypertension in TS
      patients, independent of age and BMI, and not related to other structural heart
      disease. We suggest that aortic arch morphology should be included in the risk
      stratification for hypertension in TS and propose a new quantitative method to
      express aortic arch morphology. 

PMID- 24935218
TI  - Risk factors for rehospitalization in heart failure with preserved ejection
      fraction compared with reduced ejection fraction.
AB  - Although there have been several studies regarding heart failure with preserved
      ejection fraction (HFpEF), investigations of the risk factors for readmission of
      Japanese patients with HFpEF remain scarce. Therefore, our goal was to identify
      the risk factors for readmission of Japanese patients with heart failure (HF),
      particularly those with HFpEF. We analyzed 310 patients who were hospitalized for
      the first time with HF. Preserved EF was defined EF >=50 %, and reduced EF (rEF)
      was EF <50 %. The study endpoint was readmission for HF after discharge. Medical
      history, vital signs, electrocardiograms, chest radiographs, blood tests and
      echocardiograms were compared between patients with HFpEF and with HFrEF. Among
      the 142 patients who had HFpEF, 43 reached the endpoint within 1 year.
      Multivariate analysis revealed depression (HR: 7.185), high brain natriuretic
      peptide (BNP) levels at discharge (HR: 1.003), and dilated inferior vena cava
      (HR: 1.100) as independent risk factors for readmission. In contrast, 39 of the
      168 patients with HFrEF reached the endpoint. Risk factors for readmission of
      HFrEF patients were low sodium (HR: 0.856), high blood urea nitrogen (HR: 1.045),
      high BNP levels at discharge (HR: 1.003) and absence of beta-blocker prescription
      (HR: 0.395). In conclusion, our study suggests that the predictors of HF
      readmission differ between HFpEF and HFrEF patients. 

PMID- 24935219
TI  - Embryological signaling pathways in Barrett's metaplasia development and
      malignant transformation; mechanisms and therapeutic opportunities.
AB  - Barrett's metaplasia of the esophagus (BE) is the precursor lesion of esophageal
      adenocarcinoma (EAC), a deadly disease with a 5-year overall survival of less
      than 20%. The molecular mechanisms of BE development and its transformation to
      EAC are poorly understood and current surveillance and treatment strategies are
      of limited efficacy. Increasing evidence suggests that aberrant signaling through
      pathways active in the embryological development of the esophagus contributes to
      BE development and progression to EAC. We discuss the role that the Bone
      morphogenetic protein, Hedgehog, Wingless-Type MMTV Integration Site Family (WNT)
      and Retinoic acid signaling pathways play during embryological development of the
      esophagus and their contribution to BE development and malignant transformation.
      Modulation of these pathways provides new therapeutic opportunities. By
      integrating findings in developmental biology with those from translational
      research and clinical trials, this review provides a platform for future studies
      aimed at improving current management of BE and EAC. 

PMID- 24935222
TI  - The effect of the ionic size of small quaternary ammonium BF4 salts on
      electrochemical double layer capacitors.
AB  - By varying the cation size of quaternary ammonium salts, approximately 10% higher
      capacitance was achieved with trimethylethylammonium BF4 and
      trimethylpropylammonium BF4 relative to tetraethylammonium BF4 using microporous
      activated carbon (AC) electrodes. The ions carried solvation shells in the bulk
      electrolytes, but became desolvated within the narrow AC pores when the
      electrochemical double-layer capacitor was charged to a high potential. The
      capacitance depended on the size of the cation rather than that of the BF4 anion
      because the anion is smaller than the quaternary ammonium ions. The capacitance
      was found to be proportional to the reciprocal radii of the neat cations. The
      effective radius of the asymmetric trimethylpropylammonium ion was estimated to
      be 0.314 nm based on the present results. 

PMID- 24935220
TI  - MicroRNA-26a regulates glucose metabolism by direct targeting PDHX in colorectal
      cancer cells.
AB  - BACKGROUND: Reprogramming energy metabolism has been an emerging hallmark of
      cancer cells. MicroRNAs play important roles in glucose metabolism. METHODS: The
      targets of microRNA-26a (miR-26a) were predicted by bioinformatics tools. The
      efficacy of miR-26a binding the 3'-untranslated region (UTR) of pyruvate
      dehydrogenase protein X component (PDHX) mRNA was evaluated using a dual
      luciferase reporter assay. The PDHX expression at the mRNA and protein level in
      several colon cancer cell lines was quantified with real-time PCR and Western
      blot analysis respectively. The effects of miR-26a on glucose metabolism were
      determined by detecting the content of glucose consumption, production of
      lactate, pyruvate, and acetyl-coenzyme A. RESULTS: The expression of miR-26a is
      inversely associated with the level of its targeting protein PDHX in several
      colon cancer cell lines with different malignancy potentials. MiR-26a inhibits
      PDHX expression by direct targeting the 3'-UTR of PDHX mRNA. The glucose
      consumption and lactate concentration were both greatly increased in colon cancer
      cells than the normal colon mucosal epithelia under physiological conditions. The
      overexpression of miR-26a in HCT116 cells efficiently improved the accumulation
      of pyruvate and decreased the production of acetyl coenzyme A. Meanwhile the
      inhibition of miR-26a expression induced inverse biological effects. CONCLUSIONS:
      MiR-26a regulates glucose metabolism of colorectal cancer cells by direct
      targeting the PDHX, which inhibits the conversion of pyruvate to acetyl coenzyme
      A in the citric acid cycle.

PMID- 24935221
TI  - Study protocol for improving asthma outcomes through cross-cultural communication
      training for physicians: a randomized trial of physician training.
AB  - BACKGROUND: Massive resources are expended every year on cross-cultural
      communication training for physicians. Such training is a focus of continuing
      medical education nationwide and is part of the curriculum of virtually every
      medical school in America. There is a pressing need for evidence regarding the
      effects on patients of cross-cultural communication training for physicians.
      There is a need to understand the added benefit of such training compared to more
      general communication. We know of no rigorous study that has assessed whether
      cross-cultural communication training for physicians results in better health
      outcomes for their patients. The current study aims to answer this question by
      enhancing the Physician Asthma Care Education (PACE) program to cross cultural
      communication (PACE Plus), and comparing the effect of the enhanced program to
      PACE on the health outcomes of African American and Latino/Hispanic children with
      asthma. METHODS/DESIGN: A three-arm randomized control trial is used to compare
      PACE Plus, PACE, and usual care. Both PACE and PACE Plus are delivered in two,
      two-hour sessions over a period of two weeks to 5-10 primary care physicians who
      treat African American and Latino/Hispanic children with asthma. One hundred
      twelve physicians and 1060 of their pediatric patients were recruited who self
      identify as African American or Latino/Hispanic and experience persistent asthma.
      Physicians were randomized into receiving either the PACE Plus or PACE
      intervention or into the control group. The comparative effectiveness of PACE and
      PACE Plus on clinician's therapeutic and communication practices with the
      family/patient, children's urgent care use for asthma, asthma control, and
      quality of life, and parent/caretaker satisfaction with physician performance
      will be assessed. Data are collected via telephone survey and medical record
      review at baseline, 9 months following the intervention, and 21 months following
      the intervention. DISCUSSION: This study aims to reduce disparities in asthma
      outcomes among African American and Latino/Hispanic children through cross
      cultural communication training of their physicians and assessing the added value
      of this training compared to general communication. The results of this study
      will provide important information about the value of cross-cultural training in
      helping to address persistent racial disparities in outcomes. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01251523 December 1, 2010.

PMID- 24935224
TI  - Adding social services to US clinical care makes "good business sense," report
      argues.

PMID- 24935223
TI  - Blood soluble interleukin 1 receptor accessory protein levels are consistently
      low throughout the menstrual cycle of women with endometriosis.
AB  - BACKGROUND: A deficiency in the counter-regulatory mechanisms of interleukin 1
      (IL1) may play a significant role in endometriosis pathogenesis and associated
      chronic inflammation. The aim of this study was to investigate peripheral blood
      levels of soluble IL1 receptor accessory protein (sIL1RAP), a potent natural
      inhibitor of IL1, in women with and without endometriosis. METHODS: Peripheral
      blood samples were collected from women with endometriosis (n = 47) consulting
      for infertility, pelvic pain or tubal ligation, in whom the disease was diagnosed
      at laparoscopy. Control healthy women (n = 27) were requesting tubal ligation or
      reanastomosis and had no visible evidence of endometriosis at laparoscopy.
      sIL1RAP levels were determined by ELISA, whereas estradiol (E2) and progesterone
      (P4) levels were determined by competitive immunoassays. RESULTS: sIL1RAP levels
      were significantly decreased in women with early endometriosis stages compared to
      controls (p < 0.05) and markedly during the proliferative phase of the menstrual
      cycle (p < 0.001). Actually, while sIL1RAP were significantly increased in the
      proliferative compared to the secretory phase in normal women (p < 0.0001) and
      peaked at the end of this phase, sIL1RAP remained consistently low and showed non
      significant variations throughout the menstrual cycle in women with
      endometriosis. CONCLUSIONS: Lower circulating levels of sIL1RAP points to a
      significant impairment in the counter-regulatory mechanisms of IL1, which in view
      of the cytokine's potent inflammatory and growth-promoting properties may play a
      significant role in the pathophysiology of endometriosis.

PMID- 24935225
TI  - Glial calcium signalling in Alzheimer's disease.
AB  - The most accredited (and fashionable) hypothesis of the pathogenesis of Alzheimer
      Disease (AD) sees accumulation of beta-amyloid protein in the brain (in both
      soluble and insoluble forms) as a leading mechanism of neurotoxicity. How beta
      amyloid triggers the neurodegenerative disorder is at present unclear, but
      growing evidence suggests that a deregulation of Ca(2+) homeostasis and deficient
      Ca(2+) signalling may represent a fundamental pathogenic factor. Given that
      symptoms of AD are most likely linked to synaptic dysfunction (at the early
      stages) followed by neuronal loss (at later and terminal phases of the disease),
      the effects of beta-amyloid have been mainly studied in neurones. Yet, it must be
      acknowledged that neuroglial cells, including astrocytes, contribute to
      pathological progression of most (if not all) neurological diseases. Here, we
      review the literature pertaining to changes in Ca(2+) signalling in astrocytes
      exposed to exogenous beta-amyloid or in astrocytes from transgenic Alzheimer
      disease animals models, characterized by endogenous beta-amyloidosis. Accumulated
      experimental data indicate deregulation of Ca(2+) homeostasis and signalling in
      astrocytes in AD, which should be given full pathogenetic consideration. Further
      studies are warranted to comprehend the role of deficient astroglial Ca(2+)
      signalling in the disease progression. 

PMID- 24935226
TI  - Effectiveness of two strategies to follow-up ASC-US and LSIL screening results in
      The Netherlands using repeat cytology with or without additional hrHPV testing: a
      retrospective cohort study.
AB  - PURPOSE: The purpose of the study was to assess the effectiveness of repeat
      cytology with and without additional high-risk human papilloma virus (hrHPV)
      testing after atypical squamous cells of undetermined significance/low-grade
      squamous intraepithelial lesion (ASC-US/LSIL) screening results. METHODS: In the
      Netherlands, ASC-US/LSIL is triaged by repeat cytology at 6 months or repeat
      cytology at 6 months with additional hrHPV testing. ASC-US/LSIL results from
      13,734 screenees in 2008 were extracted from "Dutch Pathology Registry" including
      cytology, histology, and/or HPV follow-up results. Proportions of compliance,
      repeat cytology, referral, and detected cervical intraepithelial neoplasia (CIN)
      were assessed. RESULTS: With additional hrHPV testing, 46.8 % was send back to
      regular screening at 6 months, 28.6 % needed second repeat cytology, and 24.6 %
      was referred for colposcopy. Without additional hrHPV testing, this was 0.0,
      76.1, and 23.9 %, respectively. With additional hrHPV testing, significantly
      higher proportions of persisting ASC-US/LSIL; compliance with repeat/referral
      advices; and histological detection of CIN0 (no CIN or cancer), CIN1, and CIN2
      were found but equal proportions CIN3+. CONCLUSIONS: Additional hrHPV testing
      shortens follow-up without altering CIN3+ detection. Detection of CIN0, CIN1, and
      CIN2 was higher, presumably by hrHPV-driven biased cytology and detection bias.
      Restricting additional hrHPV testing to older women, reading cytology without
      knowledge of hrHPV status, and addition of more specific triage tests could
      further improve the effectiveness of additional hrHPV testing.

PMID- 24935227
TI  - Over-expression of prolyl hydroxylase-1 blocks NF-kappaB-mediated cyclin D1
      expression and proliferation in lung carcinoma cells.
AB  - Prolyl hydroxylase-1 (PHD1), a member of the hypoxia inducible factor (HIF)-PHD
      family, plays an important role in regulating the stability of HIFs. The nuclear
      factor-kappaB (NF-kappaB) pathway consists of a family of transcription factors
      that play critical roles in inflammation, immunity, cell proliferation,
      differentiation, and survival. In this study, we demonstrate that PHD1 can
      inhibit NF-kappaB activity and its target genes in lung cancer cells based on
      both over-expression and RNA interference-mediated knockdown of PHD1 in human
      A549 lung cancer cells and HEK293 T cells. Of medical importance, PHD1 could
      induce cell cycle arrest in lung cancer cells, resulting in the suppression of
      cell proliferation. Xenograft tumor growth assays indicate that PHD1 plays a
      critical role in suppressing lung cancer growth. These findings reveal a new role
      of PHD1 in lung cancer and provide new treatment perspectives for cancer therapy
      by characterizing PHD1 as a potential target. 

PMID- 24935228
TI  - Analysis of gas exchange, stomatal behaviour and micronutrients uncovers dynamic
      response and adaptation of tomato plants to monochromatic light treatments.
AB  - Light spectrum affects the yield and quality of greenhouse tomato, especially
      over a prolonged period of monochromatic light treatments. Physiological and
      chemical analysis was employed to investigate the influence of light spectral
      (blue, green and red) changes on growth, photosynthesis, stomatal behaviour, leaf
      pigment, and micronutrient levels. We found that plants are less affected under
      blue light treatment, which was evident by the maintenance of higher A, gs, Tr,
      and stomatal parameters and significantly lower VPD and Tleaf as compared to
      those plants grown in green and red light treatments. Green and red light
      treatments led to significantly larger increase in the accumulation of Fe, B, Zn,
      and Cu than blue light. Moreover, guard cell length, width, and volume all showed
      highly significant positive correlations to gs, Tr and negative links to VPD.
      There was negative impact of monochromatic lights-induced accumulation of Mn, Cu,
      and Zn on photosynthesis, leaf pigments and plant growth. Furthermore, most of
      the light-induced significant changes of the physiological traits were partially
      recovered at the end of experiment. A high degree of morphological and
      physiological plasticity to blue, green and red light treatments suggested that
      tomato plants may have developed mechanisms to adapt to the light treatments.
      Thus, understanding the optimization of light spectrum for photosynthesis and
      growth is one of the key components for greenhouse tomato production. 

PMID- 24935229
TI  - Heterologous expression and functional characterization of the NADPH-cytochrome
      P450 reductase from Capsicum annuum.
AB  - Two NADPH-cytochrome P450 reductase (CPR) genes (CaCPR1 and CaCPR2) were isolated
      from hot pepper (Capsicum annuum L. cv. Bukang). At the red ripe stage, the
      expression level of CaCPR1 was more than 6-fold greater than that in leaves or
      flowers. It gradually increased during fruit ripening. The CaCPR2 gene seemed to
      be expressed constitutively in all of the tested tissues. To investigate the
      enzymatic properties of CaCPR1, the cDNA of CaCPR1 was heterologously expressed
      in Escherichia coli without any modification of amino acid sequences, and CaCPR1
      was purified. The enzymatic properties of CaCPR1 were confirmed using cytochrome
      c and cytochrome b5 as protein substrates. The CaCPR1 could support human CYP1A2
      catalyzed reaction. It also reduced tetrazolium salts and ferricyanide. These
      results show that CaCPR1 is the major CPR in most hot pepper tissues. It is
      suggested that the CaCPR1 can be used a prototype for studying biological
      functions and biotechnological applications of plant CPRs. 

PMID- 24935230
TI  - ABO blood group influences transfusion and survival after cardiac surgery.
AB  - ABO dependent variation in von Willebrand factor (vWf) and procoagulant factor
      VIII (FVIII) is a plausible mechanism for modulating perioperative hemostasis and
      bleeding. Group AB has the highest and group O the lowest vWf and FVIII levels.
      Therefore, we tested the hypothesis that ABO blood group is associated with
      perioperative transfusion and subsequent survival after coronary
      revascularization. This retrospective study combined demographic, operative, and
      transfusion data, including follow-up for a median of 2,096 days, for consecutive
      aortocoronary bypass (CABG) and CABG/valve procedures from 1996-2009 at a
      tertiary referral University Heart Center. Between group differences were
      compared by a Kruskall Wallis test, and hazard ratios [95% confidence intervals]
      are reported for mortality risk-adjusted Cox proportional hazards regression
      analysis. From 15,454 patients, follow-up records were available for 13,627
      patients: 6,413 group O, 5,248 group A, 1,454 group B, and 435 group AB. Packed
      red blood cells were the most commonly transfused blood product (3 [0-5] units),
      while group AB received 2 [0-5] units (Kruskall Wallis Chi squared value for
      between group differences = 8.2; p = 0.04). Group AB favored improved long-term,
      postoperative survival (Hazard ratio = 0.82 [95%CI 0.68-0.98]; p = 0.03), which
      became evident approximately a year after surgery. In conclusion, the
      procoagulant phenotype of blood group AB is associated with fewer transfusions
      and improved late survival after cardiac surgery. Whether this finding is related
      to fewer perioperative transfusions, a reduction in later bleeding or other
      mechanisms remains speculative.

PMID- 24935231
TI  - Correlation and disorder, in honour of Balazs Gyorffy.

PMID- 24935233
TI  - Concept Analysis: Health-Promoting Behaviors Related to Human Papilloma Virus
      (HPV) Infection.
AB  - PROBLEM: The concept of health-promoting behaviors incorporates ideas presented
      in the Ottawa Charter of Public Health and the nursing-based Health Promotion
      Model. Despite the fact that the concept of health-promoting behaviors has a
      nursing influence, literature suggests nursing has inadequately developed and
      used this concept within nursing practice. A further review of literature
      regarding health promotion behaviors and the human papilloma virus suggest a
      distinct gap in nursing literature. METHOD: This article presents a concept
      analysis of health-promoting behaviors related to the human papilloma virus in
      order to encourage the application of the concept into nursing practice, promote
      continued nursing research regarding this concept, and further expand the
      application of health-promoting behaviors to other situations and populations
      within the nursing discipline. CONCLUSION: Attributes of health-promoting
      behaviors are presented and include empowerment, participation, community, and a
      positive concept of health. Antecedents, consequences, and empirical referents
      are also presented, as are model, borderline, and contrary cases to help clarify
      the concept. Recommendations for human papilloma virus health-promoting behaviors
      within the nursing practice are also provided.

PMID- 24935232
TI  - Serum phosphorus and mortality in the Third National Health and Nutrition
      Examination Survey (NHANES III): effect modification by fasting.
AB  - BACKGROUND: Serum phosphorus levels have been associated with mortality in some
      but not all studies. Because dietary intake prior to measurement can affect serum
      phosphorus levels, we hypothesized that the association between serum phosphorus
      level and mortality is strongest in those who have fasted longer. STUDY DESIGN:
      Prospective cohort study. SETTING & PARTICIPANTS: Nationally representative
      sample of 12,984 participants 20 years or older in the Third National Health and
      Nutrition Examination Survey (1988-1994). FACTORS: Serum phosphorus level,
      fasting duration (dichotomized as >= 12 or < 12 hours). OUTCOMES: All-cause and
      cardiovascular mortality determined by death certificate data from the National
      Death Index. MEASUREMENTS: Serum phosphorus measured in a central laboratory and
      fasting duration recorded as time since food or drink other than water was
      consumed. RESULTS: Individuals fasting 12 or more hours had lower serum
      phosphorus levels than those fasting less than 12 hours (3.34 vs 3.55 mg/dL; P <
      0.001) and higher correlation with repeat measurement (0.66 vs 0.53; P = 0.002).
      In multivariable-adjusted Cox regression models, the highest quartile of serum
      phosphorus was associated with increased mortality in participants fasting 12 or
      more hours (adjusted HR, 1.74; 95% CI, 1.38-2.20; reference, lowest quartile) but
      not in participants fasting less than 12 hours (adjusted HR, 1.08; 95% CI, 0.89
      1.32; P for interaction = 0.002). Relationships were consistent using 8 hours as
      the fasting cutoff point or cardiovascular mortality as the outcome. LIMITATIONS:
      Observational study, lack of fibroblast growth factor 23 or intact parathyroid
      hormone measurements. CONCLUSIONS: Fasting but not nonfasting serum phosphorus
      levels were associated with increased mortality. Risk prognostication based on
      serum phosphorus may be improved using fasting levels.

PMID- 24935235
TI  - Functional correlates of vertical gaze palsy and other ocular motor deficits in
      PSP: an FDG-PET study.
AB  - OBJECTIVE: To determine the functional correlates of vertical gaze palsy and
      other ocular motor deficits in patients with progressive supranuclear palsy (PSP)
      using [(18)F]fluorodeoxyglucose (FDG-)PET. METHODS: Twenty-six patients with PSP
      underwent clinical examination of vertical gaze combined with FDG-PET scans to
      assess regional cerebral glucose metabolism as a marker of neuronal activity. Of
      these, eighteen PSP patients were also investigated by electrical nystagmography
      to determine horizontal ocular motor deficits. Statistical parametric mapping
      analyses were performed to correlate regional neuronal activity with ocular motor
      functions. RESULTS: In categorical comparisons, patients with downward gaze palsy
      showed a significantly reduced glucose metabolism in bilateral anterior cingulate
      gyrus and right lingual gyrus compared to those without downward gaze palsy.
      Maximum velocity of horizontal saccades was positively correlated with glucose
      metabolism of the rostral vermis and lingual gyrus; regional metabolism of
      oculomotor vermis was associated with peak velocity of the optokinetic reflex.
      Analysis of smooth pursuit eye movement amplitude and peak velocity of corrective
      saccades showed positive correlation with metabolism in bilateral inferior
      parietal lobe and inferior part of the frontal eye field. All paradigms of smooth
      pursuit showed positive association with glucose metabolism in V5. CONCLUSIONS:
      Ocular motor functions in PSP are correlated with neuronal activity in distinct
      anatomical regions. These include the anterior cingulate gyrus (downward gaze
      palsy), rostral cerebellum (saccades), oculomotor vermis (optokinetic reflex) and
      inferior parietal as well as temporal regions and frontal eye field (smooth
      pursuit). These findings provide a deeper insight into the pathophysiology of PSP
      associated ocular motor abnormalities.

PMID- 24935236
TI  - Impulse control and related disorders in Mexican Parkinson's disease patients.
AB  - BACKGROUND: Impulse control disorders (ICDs) are a relatively recent addition to
      the behavioral spectrum of PD-related non-motor symptoms. Social and economic
      factors may play a role on the ICD phenotype of PD patients. OBJECTIVE: The aim
      of this study is to determine the prevalence and characterize the clinical
      profile of ICDs in a sample of low-income, low-education PD patients with no
      social security benefits from a Latin American country. METHODS: We included 300
      consecutive PD patients and 150 control subjects. The presence of ICD and related
      disorders was assessed using a structured interview. After the interview and
      neurological evaluation were concluded, all subjects completed the Questionnaire
      for Impulsive-compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS).
      RESULTS: Regarding ICDs and related disorders (hobbyism-punding), 25.6% (n = 77)
      of patients in the PD group and 16.6% (n = 25) in the control group fulfilled
      criteria for at least one ICD or related disorder (p = 0.032). There was a
      statistically significant difference in the QUIP-RS mean score between PD and
      control subjects (5.6 +/- 9.7 and 2.7 +/- 4.21, p = 0.001). The most common ICD
      was compulsive eating for both PD (8.6%) and control (2.6%) groups. CONCLUSIONS:
      The results of this study confirm that for this population, symptoms of an ICD
      are significantly more frequent in PD subjects than in control subjects.
      Nevertheless, socioeconomic differences may contribute to a lower overall
      frequency and distinct pattern of ICDs in PD patients compared with what has been
      reported in other countries.

PMID- 24935234
TI  - Multilocus sequence analysis of putative Vibrio mediterranei strains and
      description of Vibrio thalassae sp. nov.
AB  - A multilocus sequence analysis based on partial gyrB, mreB, rpoD and pyrH genes
      was undertaken with 61 putative Vibrio mediterranei/V. shilonii strains from
      different hosts (mussels, oysters, clams, coral, fish and plankton) or habitat
      (seawater and sediment) and geographical origins (Mediterranean, Atlantic and
      Pacific). A consistent grouping was obtained with individual and concatenated
      gene sequences, and the clade, comprising 54 strains, was split into three
      subclades by all methods: subclade A (40 strains, including AK1, the former type
      strain of Vibrio shilonii), subclade B (8 strains) corresponding to the species
      V. mediterranei, and subclade C (six strains) representing a new species, V.
      thalassae sp. nov., with strain MD16(T) (=CECT 8203(T)=KCTC 32373(T)) as the
      proposed type strain. Average nucleotide identity (ANI) values, determined as a
      measure of genomic similarity, confirmed these assignments, and supported that
      strains in subclade C were a different species from V. mediterranei, with ANIb
      and ANIm figures lower than 90.0%. The synonymy of V. shilonii and V.
      mediterranei was also stressed by both MLSA and ANI determinations (97.0% between
      both type strains). No connection was found between geographic origin or sample
      type and MLSA grouping.

PMID- 24935238
TI  - Metal nanoparticle-directed NiCo2O4 nanostructure growth on carbon nanofibers
      with high capacitance.
AB  - Metal nanoparticles (Ni, Co) decorated on an electrospun carbon nanofiber surface
      directed the growth of NiCo2O4 into nanorod and nanosheet morphologies. These
      metal nanoparticles served as a transition layer to strengthen the interface and
      promote charge transfer between carbon and NiCo2O4 to achieve a high capacitance
      of 781 F g(-1). 

PMID- 24935237
TI  - Differentiating drug-induced parkinsonism from Parkinson's disease: an update on
      non-motor symptoms and investigations.
AB  - Drug-induced parkinsonism is the second most common cause of parkinsonism after
      Parkinson's disease and their distinction has crucial implications in terms of
      management and prognosis. However, differentiating between these conditions can
      be challenging on a clinical ground, especially in the early stages. We therefore
      performed a review to ascertain whether assessment of non-motor symptoms, or use
      of ancillary investigations, namely dopamine transporter imaging, transcranial
      sonography of the substantia nigra, and scintigraphy for myocardial sympathetic
      innervation, can be recommended to distinguish between these conditions. Among
      non-motor symptoms, there is evidence that hyposmia can differentiate between
      patients with "pure" drug-induced parkinsonism and those with degenerative
      parkinsonism unmasked by an anti-dopaminergic drug. However, several issues,
      including smoking history and cognitive functions, can influence smell function
      assessment. Higher diagnostic accuracy has been demonstrated for dopamine
      transporter imaging. Finally, preliminary evidence exists for sympathetic cardiac
      scintigraphy to predict dopaminergic pathway abnormalities and to differentiate
      between drug-induced parkinsonism and Parkinson's disease. Imaging of the
      dopaminergic pathway seems to be the only, reasonably available, technique to aid
      the differential diagnosis between drug-induced parkinsonism and Parkinson's
      disease. 

PMID- 24935239
TI  - Microscopic background changes in brains of cynomolgus monkeys.
AB  - Brain sections from control cynomolgus monkeys (Macaca fascicularis) used in
      toxicology studies were evaluated retrospectively in order to better understand
      spontaneous background changes in this species. Hematoxylin and eosin-stained
      slides from 76 animals (38 males and 38 females) of 9 studies were examined.
      Eleven animals (9 males and 2 females) were each observed to have 1 to 3 findings
      within the brain sections examined, for a total of 19 findings. No findings were
      noted in the spinal cord. The most common finding was focal to multifocal
      perivascular infiltration of mononuclear cells, affecting the parenchyma, the
      meninges, or the choroid plexus. Additionally, focal gliosis was observed in 6
      animals and a single focus of hemosiderin deposition (coincident with focal
      gliosis and mononuclear cell infiltrate) was noted in 1 animal. Most of the glial
      foci were composed of cells consistent with microglial cells, with or without
      admixed lymphocytes. All findings were of slight or minimal severity, lacked an
      apparent cause, and were considered incidental and of negligible biologic
      significance. An awareness of the spontaneous incidence of these background
      findings may facilitate the discernment of toxicologically relevant effects when
      these findings are observed. 

PMID- 24935240
TI  - Drug safety evaluation of alemtuzumab for multiple sclerosis.
AB  - INTRODUCTION: Alemtuzumab is a humanised anti-CD52 mAb which has recently been
      licensed for the treatment of relapsing multiple sclerosis in Europe. AREAS
      COVERED: The efficacy and safety of alemtuzumab from open label, Phase II and
      Phase III trials is reported. EXPERT OPINION: Alemtuzumab causes rapid and
      profound complement mediated lysis of circulating lymphocytes and allows
      beneficial modulation of the immune system during a subsequent reconstitution
      phase. Clinical trials have demonstrated superior efficacy against an active
      comparator, with reduction in annualised relapse rates and sustained accumulation
      of disability at 3 years and sustained efficacy at 5 years. The main adverse
      effects are mild to moderate infusion reactions, an increased incidence of mild
      to moderate infections and autoimmune adverse events. Thyroid disorders are the
      most common form of autoimmune adverse events, occurring in approximately one
      third of patients. Overt Graves' hyperthyroidism represents approximately half of
      these cases. Careful patient selection and structured monitoring programs allow
      for effective patient management resulting in a favourable risk benefit profile.

PMID- 24935242
TI  - Immunopathological characterization of selected mouse models of inflammatory
      bowel disease: Comparison to human disease.
AB  - Inflammatory bowel diseases (IBD) are chronic, relapsing conditions of
      multifactorial etiology. The two primary diseases of IBD are Crohn's disease (CD)
      and ulcerative colitis (UC). Both entities are hypothesized to occur in
      genetically susceptible individuals due to microbial alterations and
      environmental contributions. The exact etiopathogenesis, however, is not known
      for either disease. A variety of mouse models of CD and UC have been developed to
      investigate the pathogenesis of these diseases and evaluate treatment modalities.
      Broadly speaking, the mouse models can be divided into 4 categories: genetically
      engineered, immune manipulated, spontaneous and erosive/chemically induced. No
      one mouse model completely recapitulates the immunopathology of CD or UC, however
      each model possesses particular similarities to human IBD and offers advantageous
      for specific details of IBD pathogenesis. Here we discuss the more commonly used
      models in each category and critically evaluate how the immunopathology induced
      compares to CD or UC, as well as the advantages and disadvantages associated with
      each model. 

PMID- 24935241
TI  - Social impairment of individuals suffering from different types of chronic
      orofacial pain.
AB  - BACKGROUND: The daily life of patients suffering from orofacial pain is
      considerably impaired as compared to healthy subjects. The aim of this study was
      to investigate the influence of different categories of orofacial pain on the
      habitual life of adult individuals. METHODS: Seven hundred eighty-one individuals
      with orofacial pain were recruited from an initial sample of 1,058 patients. All
      the individuals were allocated to groups according to their diagnosis: myofascial
      pain (group A, 676 subjects, 525 females and 151 males; mean age +/- SD = 35.2 +/
      12.6), migraine (group B, 39 subjects, 29 females and 10 males; mean age +/- SD
      36.0 +/- 10.7), and both myofascial pain and migraine (group C, 66 subjects, 56
      females and 10 males, mean age +/- SD = 35.6 +/- 10.8). Characteristic pain
      intensity (CPI), disability days (DD), disability score (DS), and graded chronic
      pain intensity (GCPS) were calculated according to Research Diagnostic Criteria
      for Temporomandibular Disorders (RDC/TMD) axis II. Depression and somatization
      (nonspecific physical symptoms) scores were also calculated. RESULTS: A
      significant association between groups and GCPS categories was found (p <
      0.0001). Post hoc tests showed a significant difference between groups A and B
      and between A and C, but not between B and C. In group A, the most frequent GCPS
      score was grade II. The most frequent GCPS score in groups B and C was grade III,
      indicating a moderate limiting impairment. This score was more frequent in group
      B (41%) than in the other groups (group A = 20.6%, group C = 34.8%). GCPS grade
      IV was more frequent in group C (19.7%) than in the other groups. Group C had
      significantly higher scores for nonspecific physical symptoms than group A (p <
      0.05). CONCLUSIONS: Myofascial pain and migraine sensibly affect the common daily
      life of adult individuals. The comorbidity of both conditions determines a major
      impairment.

PMID- 24935244
TI  - The Karoo fracking debate: a christian contribution to the world communities of
      faith.
AB  - The fracking debate is a product of the tension between the environmental
      degradation it may cause, on the one hand, and on the other the greater energy
      demands of a rapidly increasing South African population with expectations of an
      ever-increasing standard of living. Shale gas fracking in the Karoo of South
      Africa promises to make vast reserves of oil and gas available to help meet a
      significant percentage of the country's energy needs for many years to come. This
      will aid development and contribute to raising the standard of living of many.
      This article seeks to apprise the South African faith communities of the
      technology and risks involved. Christian theological guidelines are presented by
      which its benefits and dangers may be interrogated so that the community may be
      able come to an informed decision as to whether or not to support fracking. 

PMID- 24935245
TI  - Corruption: Engineers are Victims, Perpetrators or Both?
AB  - This study was conducted in Serbian companies on licensed engineers and in its
      first part included a total of 336 licensed engineers who voluntarily completed
      the questionnaires about their ethical orientation and attitudes toward
      corruption and in the second part 214 engineers who participated in the first
      survey, who voluntarily evaluated their company's business operations
      characteristics. This study has clearly shown that there is a direct significant
      influence of the engineer's ethical orientations and attitudes toward corruption
      on their evaluation of the characteristics of their respective companies
      regarding business operations. This research also clearly shows that only
      engineers with a strong deontological orientation, low ethical subjectivity, and
      strong readiness to fight corruption, low corruption acceptance and high
      awareness of corruption can successfully fight corruption, improve the business
      operations of their companies and make beneficial changes to society. Otherwise,
      they should be considered as corruption perpetrators, not just as its victims. 

PMID- 24935243
TI  - Denosumab: a review of its use in postmenopausal women with osteoporosis.
AB  - Subcutaneous denosumab (Prolia((r)) [USA, Europe]; Pralia((r)) [Japan]) once
      every 6 months is indicated in several countries for the treatment of
      postmenopausal women with osteoporosis at increased or high risk for fractures
      (featured indication). In some countries, it is also indicated for use in
      postmenopausal women who have failed or are intolerant to other osteoporosis
      treatments. In several international, phase III trials (<=3 years' duration)
      involving more than 12,000 women with postmenopausal osteoporosis or low bone
      mineral density (BMD), including Asian studies, denosumab was an effective and
      generally well tolerated treatment. Relative to placebo, denosumab treatment
      significantly reduced the risk of vertebral, nonvertebral and hip fractures and
      increased BMD at all skeletal sites evaluated, including the lumbar spine and
      total hip. Furthermore, the benefits of denosumab treatment were generally
      evident after the first dose and were maintained during up to 8 years of
      treatment in an ongoing extension study. The tolerability profile of denosumab
      during this extension phase was consistent with that observed during the initial
      3-year FREEDOM trial. At 12 months, denosumab treatment increased BMD at the
      total hip, lumbar spine and/or femoral neck and reduced markers of bone turnover
      to a significantly greater extent than oral bisphosphonates in women who were
      essentially bisphosphonate-naive and in those who had switched from alendronate
      to denosumab treatment. Further clinical experience, including an ongoing
      postmarketing safety study, will more fully define the long-term safety of
      denosumab. In the meantime, denosumab is an important option for the treatment of
      women with postmenopausal osteoporosis at increased or high-risk of fractures,
      including in women at increased risk of fracture who are unable to take other
      osteoporosis treatments.

PMID- 24935246
TI  - No One Likes a Snitch.
AB  - Whistleblowers remain essential as complainants in allegations of research
      misconduct. Frequently internal to the research team, they are poorly protected
      from acts of retribution, which may deter the reporting of misconduct. In order
      to perform their important role, whistleblowers must be treated fairly. Draft
      regulations for whistleblower protection were published for public comment almost
      a decade ago but never issued (Dahlberg 2013). In the face of the growing
      challenge of research fraud, we suggest vigorous steps, to include:
      organizational responsibility to certify the accuracy of research including
      audit, required whistleblower action in the face of imminent or grave harm to
      subjects, strengthened legal protections against retaliation including prompt
      enactment of Federal whistleblower protections and consideration of criminalizing
      the most egregious cases of research misconduct. 

PMID- 24935248
TI  - In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid
      chromatography tandem mass spectrometry.
AB  - Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of
      inflammation, pain and fever and prevention of cardiovascular diseases with fewer
      side effects than its precursor, aspirin. Investigation into its metabolic
      process in target animal species will help to illustrate its mechanism of action
      and to establish its residual mark compound to formulate its dosage. Six beagle
      dogs were orally given a dose of 20 mg kg(-1) of AEE and one dog was used to
      prepare blank liver microsomes. Their liver microsomes were prepared for in vitro
      study and their plasma and urine were collected for in vivo metabolic analysis
      using liquid chromatography tandem mass spectrometry. In this study we identified
      10 metabolites, M1, M2, M3, M4, M5 in phase I and M6, M7, M8, M9, M10 in phase
      II. Based on the metabolites of AEE, the pathways of AEE metabolism in dog were
      demonstrated.

PMID- 24935247
TI  - Pinpointing retrovirus entry sites in cells expressing alternatively spliced
      receptor isoforms by single virus imaging.
AB  - BACKGROUND: The majority of viruses enter host cells via endocytosis. Current
      knowledge of viral entry pathways is largely based upon infectivity measurements
      following genetic and/or pharmacological interventions that disrupt vesicular
      trafficking and maturation. Imaging of single virus entry in living cells
      provides a powerful means to delineate viral trafficking pathways and entry sites
      under physiological conditions. RESULTS: Here, we visualized single avian
      retrovirus co-trafficking with markers for early (Rab5) and late (Rab7)
      endosomes, acidification of endosomal lumen and the resulting viral fusion
      measured by the viral content release into the cytoplasm. Virus-carrying vesicles
      either merged with the existing Rab5-positive early endosomes or slowly
      accumulated Rab5. The Rab5 recruitment to virus-carrying endosomes correlated
      with acidification of their lumen. Viral fusion occurred either in early (Rab5
      positive) or intermediate (Rab5- and Rab7-positive) compartments. Interestingly,
      different isoforms of the cognate receptor directed virus entry from distinct
      endosomes. In cells expressing the transmembrane receptor, viruses preferentially
      entered and fused with slowly maturing early endosomes prior to accumulation of
      Rab7. By comparison, in cells expressing the GPI-anchored receptor, viruses
      entered both slowly and quickly maturing endosomes and fused with early (Rab5
      positive) and intermediate (Rab5- and Rab7-positive) compartments. CONCLUSIONS:
      Since the rate of low pH-triggered fusion was independent of the receptor
      isoform, we concluded that the sites of virus entry are determined by the kinetic
      competition between endosome maturation and viral fusion. Our findings
      demonstrate the ability of this retrovirus to enter cells via alternative
      endocytic pathways and establish infection by releasing its content from distinct
      endosomal compartments.

PMID- 24935249
TI  - Endothelial cell response to chemical, biological, and physical cues in bioactive
      hydrogels.
AB  - The highly tunable biological, chemical, and physical properties of bioactive
      hydrogels enable their use in an array of tissue engineering and drug delivery
      applications. Systematic modulation of these properties can be used to elucidate
      key cell-material interactions to improve therapeutic effects. For example, the
      rate and extent of endothelialization are critical to the long-term success of
      many blood-contacting devices. To this end, we have developed a bioactive
      hydrogel that could be used as coating on cardiovascular devices to enhance
      endothelial cell (EC) adhesion and migration. The current work investigates the
      relative impact of hydrogel variables on key endothelialization processes. The
      bioactive hydrogel is based on poly(ethylene glycol) (PEG) and a streptococcal
      collagen-like (Scl2-2) protein that has been modified with integrin alpha1beta1
      and alpha2beta1 binding sites. The use of PEG hydrogels allows for incorporation
      of specific bioactive cues and independent manipulation of scaffold properties.
      The selective integrin binding of Scl2-2 was compared to more traditional
      collagen-modified PEG hydrogels to determine the effect of integrin binding on
      cell behavior. Protein functionalization density, protein concentration, and
      substrate modulus were independently tuned with both Scl2-2 and collagen to
      determine the effect of each variable on EC adhesion, spreading, and migration.
      The findings here demonstrate that increasing substrate modulus, decreasing
      functionalization density, and increasing protein concentration can be utilized
      to increase EC adhesion and migration. Additionally, PEG-Scl2-2 hydrogels had
      higher migration speeds and proliferation over 1 week compared with PEG-collagen
      gels, demonstrating that selective integrin binding can be used to enhance cell
      material interactions. Overall, these studies contribute to the understanding of
      the effects of matrix cues on EC interactions and demonstrate the strong
      potential of PEG-Scl2-2 hydrogels to promote endothelialization of blood
      contacting devices. 

PMID- 24935252
TI  - Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on
      in vitro toxicity data and in silico physiologically based kinetic modeling.
AB  - The use of laboratory animals for toxicity testing in chemical safety assessment
      meets increasing ethical, economic and legislative constraints. The development,
      validation and application of reliable alternatives for in vivo toxicity testing
      are therefore urgently needed. In order to use toxicity data obtained from in
      vitro assays for risk assessment, in vitro concentration-response data need to be
      translated into in vivo dose-response data that are needed to obtain points of
      departure for risk assessment, like a benchmark dose (BMD). In the present study,
      we translated in vitro concentration-response data of the retinoid all-trans
      retinoic acid (ATRA), obtained in the differentiation assay of the embryonic stem
      cell test, into in vivo dose-response data using a physiologically based kinetic
      model for rat and human that is mainly based on kinetic model parameter values
      derived using in vitro techniques. The predicted in vivo dose-response data were
      used for BMD modeling, and the obtained BMDL10 values [lower limit of the 95 %
      confidence interval on the BMD at which a benchmark response equivalent to a 10 %
      effect size (BMR10) is reached (BMD10)] for rat were compared with BMDL10 values
      derived from in vivo developmental toxicity data in rats reported in the
      literature. The results show that the BMDL10 values from predicted dose-response
      data differ about sixfold from the BMDL10 values obtained from in vivo data,
      pointing at the feasibility of using a combined in vitro-in silico approach for
      defining a point of departure for toxicological risk assessment. 

PMID- 24935250
TI  - Effects of NB001 and gabapentin on irritable bowel syndrome-induced behavioral
      anxiety and spontaneous pain.
AB  - Irritable bowel syndrome (IBS) is characterized by recurrent abdominal
      discomfort, spontaneous pain, colorectal hypersensitivity and bowel dysfunction.
      Patients with IBS also suffer from emotional anxiety and depression. However, few
      animal studies have investigated IBS-induced spontaneous pain and behavioral
      anxiety. In this study, we assessed spontaneous pain and anxiety behaviors in an
      adult mouse model of IBS induced by zymosan administration. By using Fos protein
      as a marker, we found that sensory and emotion related brain regions were
      activated at day 7 after the treatment with zymosan; these regions include the
      prefrontal cortex, anterior cingulate cortex, insular cortex and amygdala.
      Behaviorally, zymosan administration triggered spontaneous pain (decreased
      spontaneous activities in the open field test) and increased anxiety-like
      behaviors in three different tests (the open field, elevated plus maze and
      light/dark box tests). Intraperitoneal injection of NB001, an adenylyl cyclase 1
      (AC1) inhibitor, reduced spontaneous pain but had no significant effect on
      behavioral anxiety. In contrast, gabapentin reduced both spontaneous pain and
      behavioral anxiety. These results indicate that NB001 and gabapentin may inhibit
      spontaneous pain and anxiety-like behaviors through different mechanisms. 

PMID- 24935251
TI  - From transient transcriptome responses to disturbed neurodevelopment: role of
      histone acetylation and methylation as epigenetic switch between reversible and
      irreversible drug effects.
AB  - The superordinate principles governing the transcriptome response of
      differentiating cells exposed to drugs are still unclear. Often, it is assumed
      that toxicogenomics data reflect the immediate mode of action (MoA) of drugs.
      Alternatively, transcriptome changes could describe altered differentiation
      states as indirect consequence of drug exposure. We used here the developmental
      toxicants valproate and trichostatin A to address this question. Neurally
      differentiating human embryonic stem cells were treated for 6 days. Histone
      acetylation (primary MoA) increased quickly and returned to baseline after 48 h.
      Histone H3 lysine methylation at the promoter of the neurodevelopmental
      regulators PAX6 or OTX2 was increasingly altered over time. Methylation changes
      remained persistent and correlated with neurodevelopmental defects and with
      effects on PAX6 gene expression, also when the drug was washed out after 3-4
      days. We hypothesized that drug exposures altering only acetylation would lead to
      reversible transcriptome changes (indicating MoA), and challenges that altered
      methylation would lead to irreversible developmental disturbances. Data from
      pulse-chase experiments corroborated this assumption. Short drug treatment
      triggered reversible transcriptome changes; longer exposure disrupted
      neurodevelopment. The disturbed differentiation was reflected by an altered
      transcriptome pattern, and the observed changes were similar when the drug was
      washed out during the last 48 h. We conclude that transcriptome data after
      prolonged chemical stress of differentiating cells mainly reflect the altered
      developmental stage of the model system and not the drug MoA. We suggest that
      brief exposures, followed by immediate analysis, are more suitable for
      information on immediate drug responses and the toxicity MoA.

PMID- 24935253
TI  - Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats
      after short-term inhalation exposure.
AB  - Gold nanoparticles are known to be distributed to many tissues following their
      oral, inhalation, or intravenous exposure. Information on the biodistribution and
      clearance of gold nanoparticles from these tissues is, therefore, important to
      understand their behavior in vivo. To study the effect of size on the
      biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by
      inhalation to small gold nanoparticles (13 nm in diameter on average) at an
      exposure concentration of 12.8 +/- 2.42 ug/m(3), and to large gold nanoparticles
      (105 nm in diameter on average) at an exposure concentration of 13.7 +/- 1.32
      ug/m(3). The experimental animals were exposed to the gold nanoparticles and the
      control animals to fresh air for 5 days (6 h/day), followed by a recovery period
      of 1, 3, and 28 days in fresh air. None of the exposed animals exhibited any
      toxic response to the gold nanoparticles. Despite the difference in size, both
      small and large gold nanoparticles deposited mainly in rat lungs. Their
      biodistribution from the lungs to secondary target organs was significantly
      higher with the small compared to the large gold nanoparticles. While the large
      gold nanoparticles were only found in the blood, the small gold nanoparticles
      were detected in the liver, spleen, brain, testes, and blood. In addition, the
      elimination half-life of the small gold nanoparticles from the lungs was
      significantly shorter than that of the large gold nanoparticles. The present data
      may, therefore, suggest that the smaller gold nanoparticles are able to
      translocate from the lungs, the primary exposure organ to extrapulmonary organs
      at a faster rate than the larger gold nanoparticles and thus confirming previous
      observations reported in the literature. 

PMID- 24935255
TI  - Where is the drug gone? Measuring intracellular delivery and localization.

PMID- 24935254
TI  - Occupational exposures to polycyclic aromatic hydrocarbons and respiratory and
      urinary tract cancers: an updated systematic review and a meta-analysis to 2014.
AB  - Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with an
      excess risk of respiratory tract and bladder cancers in several industries, but
      the issue requires further quantification. We updated a previous systematic
      review by reviewing in details cohort studies on workers employed in selected
      industries with potential PAH exposure published between 2006 and 2014, and we
      summarized through a meta-analytic approach the main results of all available
      cohort studies published between 1958 and 2014 investigating cancers of the
      respiratory and urinary tracts. Thirteen papers on cohort studies investigating
      cancer risk in workers exposed to PAHs were retrieved through the literature
      search. These included workers from aluminum production industries (seven
      studies), iron and steel foundries (two studies), asphalt workers (two studies),
      and carbon black production (two studies). In the meta-analysis, an excess risk
      of respiratory tract cancers (mainly lung cancer) was found in iron and steel
      foundries [pooled relative risk (RR) 1.31, 95 % confidence interval (CI) 1.08
      1.59 from 14 studies], while a weak excess risk (pooled RR 1.08, 95 % CI 0.95
      1.23 from 11 studies) emerged for aluminum production. A borderline increase risk
      was also observed for cancer of the bladder in the aluminum production (pooled RR
      1.28, 95 % CI 0.98-1.68 from 10 studies) and in iron and steel foundries (pooled
      RR 1.38, 95 % CI 1.00-1.91 from 9 studies). This updated review and meta-analysis
      confirm the increased risk from respiratory tract and bladder cancers in selected
      PAH-related occupations. It cannot be ruled out whether such excesses are due, at
      least in part, to possible bias or residual confounding.

PMID- 24935256
TI  - Palladium-catalyzed annulation of benzynes with N-substituted-N-(2
      halophenyl)formamides: synthesis of phenanthridinones.
AB  - A novel and efficient procedure for the synthesis of N-substituted
      phenanthridinones via palladium-catalyzed annulation of benzynes with N
      substituted-N-(2-halophenyl)formamides has been developed. This methodology
      constructs two new C-C bonds via an arylation/annulation process, and provides
      the desired products in good yields. 

PMID- 24935261
TI  - Environmental factors affecting the expression of type IV pilus genes as well as
      piliation of Thermus thermophilus.
AB  - The thermophilic bacterium Thermus thermophilus HB27 is known for its highly
      efficient natural transformation system, which has become a model system to study
      the structure and function of DNA transporter in thermophilic bacteria. The DNA
      transporter is functionally linked to type IV pili (T4P), which are essential for
      twitching motility and adhesion to solid surfaces. However, the pilus structures
      themselves are dispensable for natural transformation. Here, we report that the
      cellular mRNA levels of the major structural subunit of the T4P, PilA4, are
      regulated by environmental factors. Growth of T. thermophilus in minimal medium
      or low temperature (55  degrees C) leads to a significant increase in pilA4
      transcripts. In contrast, the transcript levels of the minor pilin pilA1 as well
      as other T4P genes are nearly unaffected. The elevated pilA4 mRNA levels are
      accompanied by an increase in piliation of the cells but not by elevated natural
      transformation frequencies. Hyperpiliation leads to increased adhesion to plastic
      surfaces. The increased cell-surface interactions are suggested to represent an
      adaptive response to temperature stress and may be advantageous for survival of
      T. thermophilus.

PMID- 24935258
TI  - Cardiac fibroblasts mediate IL-17A-driven inflammatory dilated cardiomyopathy.
AB  - Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in
      individuals below the age of 40. We recently reported that IL-17A is required for
      the development of DCMi. We show a novel pathway connecting IL-17A, cardiac
      fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the
      pathogenesis of DCMi. Il17ra(-/-) mice were protected from DCMi, and this was
      associated with significantly diminished neutrophil and Ly6Chi
      monocyte/macrophage (MO/MPhi) cardiac infiltrates. Depletion of Ly6Chi MO/MPhi
      also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce
      key chemokines and cytokines that are critical downstream effectors in the
      recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi
      MO/MPhi in trans toward a more proinflammatory phenotype via CF-derived GM-CSF.
      Collectively, this IL-17A-fibroblast-GM-CSF-MO/MPhi axis could provide a novel
      target for the treatment of DCMi and related inflammatory cardiac diseases.

PMID- 24935257
TI  - A novel self-lipid antigen targets human T cells against CD1c(+) leukemias.
AB  - T cells that recognize self-lipids presented by CD1c are frequent in the
      peripheral blood of healthy individuals and kill transformed hematopoietic cells,
      but little is known about their antigen specificity and potential antileukemia
      effects. We report that CD1c self-reactive T cells recognize a novel class of
      self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are
      accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia
      blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c(+)
      acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and
      protect immunodeficient mice against CD1c(+) human leukemia cells. The
      identification of immunogenic self-lipid antigens accumulated in leukemia cells
      and the observed leukemia control by lipid-specific T cells in vivo provide a new
      conceptual framework for leukemia immune surveillance and possible immunotherapy.

PMID- 24935260
TI  - JAK2 V617F and CALR mutations are not mutually exclusive; findings from
      retrospective analysis of a small patient cohort.

PMID- 24935262
TI  - Perfluoroalkyl substance contamination of the Llobregat River ecosystem
      (Mediterranean area, NE Spain).
AB  - The occurrence and sources of 21 perfluoroalkyl substances (PFASs: C4-C14, C16,
      C18 carboxylate, C4, C6-C8 and C10 sulfonates and C8 sulfonamide) were determined
      in water, sediment, and biota of the Llobregat River basin (NE Spain). Analytes
      were extracted by solid phase extraction (SPE) and determined by liquid
      chromatography triple quadrupole mass spectrometer (LC-QqQ-MS). All samples were
      contaminated with at least one PFAS, being the most frequently found
      perfluorobutanoate (PFBA), perfluorooctanoate (PFOA) and perfluorooctane
      sulfonate (L-PFOS). In general, mean PFAS concentrations measured in sediments
      (0.01-3.67 ng g(-1)) and biota (0.79-431 MUg kg(-1)) samples were higher than
      those found in water (0.01-233 ng L(-1)). L-PFOS presented very high levels in
      biota and water, particularly in the Anoia River where a maximum concentration of
      2.71 MUg L(-1) was related to important industrial activities. However, this
      pollution does not extend down the Llobregat River according to cumulated values.
      None of the hazard quotients (HQ) calculated indicate potential risk for the
      different tropic levels considered (algae, Daphnia sp. and fish). According to
      Maximum Allowable Concentration (MAC) proposed by the European Commission (L
      PFOS) and to Provisional Health Advisory (PHA) values (PFOA, L-PFOS) established
      by the United States Environmental Protection Agency (US EPA), only two water
      samples exceeded PHA concentration for L-PFOS.

PMID- 24935259
TI  - CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting
      cells via cognate interaction with MOG.
AB  - Myelin oligodendrocyte glycoprotein (MOG), a constituent of central nervous
      system myelin, is an important autoantigen in the neuroinflammatory disease
      multiple sclerosis (MS). However, its function remains unknown. Here, we show
      that, in healthy human myelin, MOG is decorated with fucosylated N-glycans that
      support recognition by the C-type lectin receptor (CLR) DC-specific intercellular
      adhesion molecule-3-grabbing nonintegrin (DC-SIGN) on microglia and DCs. The
      interaction of MOG with DC-SIGN in the context of simultaneous TLR4 activation
      resulted in enhanced IL-10 secretion and decreased T cell proliferation in a DC
      SIGN-, glycosylation-, and Raf1-dependent manner. Exposure of oligodendrocytes to
      proinflammatory factors resulted in the down-regulation of fucosyltransferase
      expression, reflected by altered glycosylation at the MS lesion site. Indeed,
      removal of fucose on myelin reduced DC-SIGN-dependent homeostatic control, and
      resulted in inflammasome activation, increased T cell proliferation, and
      differentiation toward a Th17-prone phenotype. These data demonstrate a new role
      for myelin glycosylation in the control of immune homeostasis in the healthy
      human brain through the MOG-DC-SIGN homeostatic regulatory axis, which is
      comprised by inflammatory insults that affect glycosylation. This phenomenon
      should be considered as a basis to restore immune tolerance in MS.

PMID- 24935263
TI  - Recent progress on our understanding of the biological effects of mercury in fish
      and wildlife in the Canadian Arctic.
AB  - This review summarizes our current state of knowledge regarding the potential
      biological effects of mercury (Hg) exposure on fish and wildlife in the Canadian
      Arctic. Although Hg in most freshwater fish from northern Canada was not
      sufficiently elevated to be of concern, a few lakes in the Northwest Territories
      and Nunavut contained fish of certain species (e.g. northern pike, Arctic char)
      whose muscle Hg concentrations exceeded an estimated threshold range (0.5-1.0 MUg
      g(-1) wet weight) within which adverse biological effects begin to occur. Marine
      fish species generally had substantially lower Hg concentrations than freshwater
      fish; but the Greenland shark, a long-lived predatory species, had mean muscle Hg
      concentrations exceeding the threshold range for possible effects on health or
      reproduction. An examination of recent egg Hg concentrations for marine birds
      from the Canadian Arctic indicated that mean Hg concentration in ivory gulls from
      Seymour Island fell within the threshold range associated with adverse effects on
      reproduction in birds. Mercury concentrations in brain tissue of beluga whales
      and polar bears were generally lower than levels associated with neurotoxicity in
      mammals, but were sometimes high enough to cause subtle neurochemical changes
      that can precede overt neurotoxicity. Harbour seals from western Hudson Bay had
      elevated mean liver Hg concentrations along with comparatively high muscle Hg
      concentrations indicating potential health effects from methylmercury (MeHg)
      exposure on this subpopulation. Because current information is generally
      insufficient to determine with confidence whether Hg exposure is impacting the
      health of specific fish or wildlife populations in the Canadian Arctic,
      biological effects studies should comprise a major focus of future Hg research in
      the Canadian Arctic. Additionally, studies on cellular interactions between Hg
      and selenium (Se) are required to better account for potential protective effects
      of Se on Hg toxicity, especially in large predatory Arctic fish, birds, and
      mammals.

PMID- 24935264
TI  - Novel complex disease allele mutations in cleidocranial dysplasia patients.
AB  - This study reports a novel identical complex disease allele harboring two non
      synonymous mutations that were identified in two southern Chinese individuals of
      the same family with cleidocranial dysplasia (CCD). Blood samples were obtained
      from the proband, his parents, plus 100 matched control subjects. Exons 0 to 7 of
      the RUNX2 gene were amplified using specific primers and sequenced. Multiple
      sequence alignment and protein structure modeling was performed using ClustalW2
      and MODBASE software while PolyPhen-2 and MutationTaster applications were
      employed to predict the disease-causing potential of the identified mutations. A
      complex disease allele in two affected individuals harboring two non-synonymous
      mutations in a cis-position on exons 4 (D273N) and 5 (P299L) were identified. The
      identified mutations were in the conserved region and changed the protein
      structure. 

PMID- 24935265
TI  - Development of an in vitro liquid chromatography-mass spectrometry method to
      evaluate stereo and chemical stability of new drug candidates employing
      immobilized artificial membrane column.
AB  - A stopped-flow HPLC method was developed to evaluate configurational and chemical
      stability of pharmaceutical compounds employing immobilized artificial membranes
      (IAM) column to simulate conditions that pharmaceutical compounds will meet in
      vivo. The method was applied to recent developed chiral 5-arylbenzothiadiazine
      derivatives possessing high positive allosteric modulatory (PAM) activity on AMPA
      receptor. In particular the stopped-flow HPLC method developed used a chiral
      column to separate single enantiomer of the compounds that are forced into an IAM
      column where configurational and chemical stability was evaluated in simulated
      gastrointestinal fluids (pH 1.2 and 6.8 at 37.5  degrees C) to simulate in vivo
      conditions. The results were compared to those obtained by dynamic and off-column
      methods to evaluate the effects of stationary phases on kinetic constant of
      enantiomerization and hydrolysis. The results suggested that the phospholipids
      environment of IAM stationary phases, which mimes biological membrane, greatly
      influence the hydrolysis process increasing the chemical stability of tested
      compounds while no influence on enantiomerization kinetic was observed. Therefore
      it is possible to suppose that 5-arylbenzothiadiazine derivatives should not
      hydrolysed in vivo while they should rapidly racemized in aqueous solvents. The
      method could represents a rapid and value tool to predict chemical and
      configurational stability of new chemical entities to decrease the number of
      animal studies.

PMID- 24935266
TI  - Stir-membrane solid-liquid-liquid microextraction for the determination of
      parabens in human breast milk samples by ultra high performance liquid
      chromatography-tandem mass spectrometry.
AB  - In this article, stir-membrane solid-liquid-liquid microextraction (SM-SLLME) is
      tailored for the analysis of solid matrices and it has been evaluated for the
      determination of parabens in l breast milk samples. A three-phase microextraction
      mode was used for the extraction of the target compounds taking advantage of
      their acid-base properties. The unit allows the simultaneous extraction of the
      target compounds from the solid sample to an organic media and the subsequent
      transference of the analytes to an aqueous acceptor phase. The method includes
      the identification and quantification of the analytes by ultra high performance
      liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). All the
      variables involved in the extraction procedure have been accurately studied and
      optimized. The analytes were detected and quantified using a triple quadrupole
      mass spectrometer (QqQ). The selection of two specific fragmentation transitions
      for each compound allowed simultaneous quantification and identification. The
      method has been analytically characterized on the basis of its linearity,
      sensitivity and precision. Limits of detection ranged from 0.1 to 0.2ngmL(-1)
      with precision better than 8%, (expressed as relative standard deviation).
      Relative recoveries were in the range from 91 to 106% which demonstrated the
      applicability of the stir-membrane solid-liquid-liquid microextraction for the
      proposed analytical problem. Moreover, the method has been satisfactorily applied
      for the determination of parabens in lyophilized breast milk samples from 10
      randomly selected individuals. 

PMID- 24935267
TI  - Molecular imprinted polymeric porous layers in open tubular capillaries for
      chiral separations.
AB  - A new method has been developed for the preparation of molecular imprinted
      polymers as porous layers in open tubular (MIP-PLOT) capillary column formats for
      use in chiral separations by capillary liquid chromatography. The synthesis was
      based on 'in-capillary' ultraviolet (UV) initiated polymerization using light
      emitting diodes (LEDs) in conjunction with the continuous delivery of the pre
      polymerization reagents into the polymerization zone of the capillary using an
      automated capillary delivery device. The relationships between exposure times, UV
      light intensity and polymer layer thickness have been determined, as well as the
      effects of reagent delivery rate and multiple LED exposures on the layer
      thickness for various compositions of pre-polymerization mixtures. The polymer
      surface morphology was investigated by scanning electron microscopy (SEM). The
      non-steroidal anti-inflammatory drug S-ketoprofen was used as the template for
      the preparation of the MIP imprinted PLOT coatings. The separation performance
      with the ketoprofen racemate was investigated by capillary liquid chromatography.
      In contrast to alternative methods, which require the use of expensive chiral
      selectors, the described MIP PLOT stationary phases used non-chiral polymer
      precursors to create enantioselective nano-cavities through molecular self
      assembly processes. The described fabrication methods provide a new avenue to
      tailor-make chiral MIP-PLOT capillary columns for the separation of chiral
      compounds present in complex or racemic analyte mixtures of chemical and
      biological origin. 

PMID- 24935268
TI  - Tuning the giant magnetoelastic transition in Ba3BiIr2O9 and Ba3BiRu2O9.
AB  - We have experimentally investigated the effects of pressure on the magnetoelastic
      transitions associated with the opening of spin-gaps in Ba3BiIr2O9 and
      Ba3BiRu2O9. For both compounds, reducing the unit cell volume by either external
      physical and internal chemical pressure was found to reduce the temperature T(*)
      of the transition and, to a lesser extent, the magnitude of the associated
      negative thermal volume expansion. The results yield the latent heat associated
      with the transitions, -3.34(3) * 10(2) J mol(-1) for Ba3BiIr2O9 and -7.1(5) *
      10(2) J mol(-1) for Ba3BiRu2O9. The transition in Ba3BiRu2O9 is significantly
      more robust than in Ba3BiIr2O9, requiring an order of magnitude higher pressures
      to achieve the same reduction in T(*). The differing responses of the two
      compounds points to differences between the 4d and 5d metals and hence to the
      importance of spin-orbit coupling, which is expected to be much stronger in the
      Ir compound. 

PMID- 24935270
TI  - ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug
      induced liver injury.
AB  - Idiosyncratic drug-induced liver injury (DILI) is a rare adverse drug reaction
      and it can lead to jaundice, liver failure, or even death. Antimicrobials and
      herbal and dietary supplements are among the most common therapeutic classes to
      cause DILI in the Western world. DILI is a diagnosis of exclusion and thus
      careful history taking and thorough work-up for competing etiologies are
      essential for its timely diagnosis. In this ACG Clinical Guideline, the authors
      present an evidence-based approach to diagnosis and management of DILI with
      special emphasis on DILI due to herbal and dietary supplements and DILI occurring
      in individuals with underlying liver disease. 

PMID- 24935269
TI  - Novel serum protein biomarker panel revealed by mass spectrometry and its
      prognostic value in breast cancer.
AB  - INTRODUCTION: Serum profiling using proteomic techniques has great potential to
      detect biomarkers that might improve diagnosis and predict outcome for breast
      cancer patients (BC). This study used surface-enhanced laser
      desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) to
      identify differentially expressed proteins in sera from BC and healthy volunteers
      (HV), with the goal of developing a new prognostic biomarker panel. METHODS:
      Training set serum samples from 99 BC and 51 HV subjects were applied to four
      adsorptive chip surfaces (anion-exchange, cation-exchange, hydrophobic, and metal
      affinity) and analyzed by time-of-flight MS. For validation, 100 independent BC
      serum samples and 70 HV samples were analyzed similarly. Cluster analysis of
      protein spectra was performed to identify protein patterns related to BC and HV
      groups. Univariate and multivariate statistical analyses were used to develop a
      protein panel to distinguish breast cancer sera from healthy sera, and its
      prognostic potential was evaluated. RESULTS: From 51 protein peaks that were
      significantly up- or downregulated in BC patients by univariate analysis, binary
      logistic regression yielded five protein peaks that together classified BC and HV
      with a receiver operating characteristic (ROC) area-under-the-curve value of
      0.961. Validation on an independent patient cohort confirmed the five-protein
      parameter (ROC value 0.939). The five-protein parameter showed positive
      association with large tumor size (P = 0.018) and lymph node involvement (P =
      0.016). By matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
      MS, immunoprecipitation and western blotting the proteins were identified as a
      fragment of apolipoprotein H (ApoH), ApoCI, complement C3a, transthyretin, and
      ApoAI. Kaplan-Meier analysis on 181 subjects after median follow-up of >5 years
      demonstrated that the panel significantly predicted disease-free survival (P =
      0.005), its efficacy apparently greater in women with estrogen receptor (ER)
      negative tumors (n = 50, P = 0.003) compared to ER-positive (n = 131, P = 0.161),
      although the influence of ER status needs to be confirmed after longer follow-up.
      CONCLUSIONS: Protein mass profiling by MS has revealed five serum proteins which,
      in combination, can distinguish between serum from women with breast cancer and
      healthy control subjects with high sensitivity and specificity. The five-protein
      panel significantly predicts recurrence-free survival in women with ER-negative
      tumors and may have value in the management of these patients.

PMID- 24935271
TI  - Anatomic and advanced adenoma detection rates as quality metrics determined via
      natural language processing.
AB  - OBJECTIVES: The objectives of this study were to use an open-source natural
      language-processing tool (NLP) to accurately assess total, anatomic (left and
      right colon), and advanced adenoma detection rates (ADRs) and to determine how
      these metrics differ between high- and low-performing endoscopists. METHODS: An
      NLP tool was developed using the Apache Unstructured Information Management
      Architecture and queried all procedure records for screening colonoscopies
      performed in patients aged 50-75 years at a single institution from April 1998 to
      December 2013. Validation was performed on 200 procedures and associated
      pathology reports. The total, left colon, right colon, and advanced ADRs were
      calculated and physicians were stratified by total ADR (<20% and >=20%).
      Comparisons of colonoscopy characteristics and ADR comparisons (advanced, left,
      right, and right/left ratio) were determined by t-tests and Wilcoxon rank-sum
      tests. RESULTS: The total ADR for 34,998 screening colonoscopies from 1998 to
      2013 was 20.3%, as determined via NLP. The institutional left and right colon
      ADRs were 10.1% and 12.5%, respectively. The overall advanced ADR was 4.4%.
      Endoscopists with total ADRs >=20% had higher left (12.4%) and right colon
      (16.4%) ADRs than endoscopists with ADRs <20% (left ADR=5.6%, right ADR=5.8%).
      Endoscopists with ADRs >=20% had higher individual right/left ADR ratios than
      those with low ADRs (1.4 (interquartile range (IQR) 0.4) vs. 1.0 (IQR 0.4),
      P=0.02). There was a moderate positive correlation between advanced ADR detection
      and both right (Spearman's rho=0.5, P=0.05) and left colon (Spearman's rho=0.4,
      P=0.03) ADRs. CONCLUSIONS: Institutions should consider the use of anatomic and
      advanced ADRs determined via natural language processing as a refined measure of
      colonoscopy quality. The ability to continuously monitor and provide feedback on
      colonoscopy quality metrics may encourage endoscopists to refine technique,
      resulting in overall improvements in adenoma detection.

PMID- 24935272
TI  - Granulocyte colony-stimulating factor in severe alcoholic hepatitis: a randomized
      pilot study.
AB  - OBJECTIVES: Severe alcoholic hepatitis has high short-term mortality. The aim of
      this study was to test the hypothesis that treatment of patients with alcoholic
      hepatitis with granulocyte colony-stimulating factor (G-CSF) might mobilize bone
      marrow-derived stem cells and promote hepatic regeneration and thus improve
      survival. METHODS: Forty-six patients with severe alcoholic hepatitis were
      prospectively randomized in an open study to standard medical therapy (SMT) plus
      G-CSF (group A; n=23) at a dose of 5 MUg/kg subcutaneously every 12 h for 5
      consecutive days or to SMT alone (group B; n=23) at a tertiary care center. We
      assessed the mobilization of CD34(+) cells on day 6, Child-Turcotte-Pugh (CTP),
      model for end-stage liver disease (MELD), and modified Maddrey's discriminant
      function (mDF) scores, and survival until day 90. RESULTS: There was a
      statistically significant increase in the number of CD34(+) cells in peripheral
      blood in group A as compared with group B (P=0.019) after 5 days of G-GSF
      therapy. There was a significant reduction in median Delta change% in CTP, MELD,
      and mDF at 1, 2, and 3 months in group A as compared with group B (P<0.05). There
      was marked improvement in survival in group A as compared with group B (78.3% vs.
      30.4%; P=0.001) at 90 days. CONCLUSIONS: G-CSF is safe and effective in the
      mobilization of hematopoietic stem cells and improves liver function as well as
      survival in patients with severe alcoholic hepatitis.

PMID- 24935273
TI  - Informed choice vs. no choice in colorectal cancer screening tests: a prospective
      cohort study in real-life screening practice.
AB  - OBJECTIVES: The objective of this study was to compare the level of adherence to
      colorectal cancer (CRC) screening programs among screening participants offered
      vs. not offered informed choices on screening modality. METHODS: We recruited
      10,606 screening participants aged 50-70 years, including 6,397 subjects who were
      offered a choice of yearly fecal immunochemical test (FIT) for up to 3 years vs.
      one colonoscopy, and 4,209 subjects who were offered either FIT or colonoscopy
      without choice. They were prospectively followed up for 3 years. The proportion
      of screening participants who returned their specimens in all subsequent years
      (FIT group) and the attendance rate of scheduled endoscopy appointment
      (colonoscopy group) were compared between those with vs. without choice. RESULTS:
      The adherence rate with FIT was 97.6%, 84.1%, and 72.6% in the first 3 years of
      follow-up, respectively, among those who were offered a choice. The adherence
      rate with FIT was 97.5%, 78.4%, and 62.8%, respectively, among those without
      choices. The proportion of subjects attending colonoscopy was 95.7% (choice
      offered) and 90.6% (no choice). From binary logistic regression analysis,
      participants who were offered informed choice were significantly more likely to
      adhere to the program when compared with those without test choices (odds ratio
      (OR)=2.54, 95% confidence interval (CI): 2.30-2.82, P<0.001). The respective
      adjusted OR for the FIT and colonoscopy groups was 1.60 (95% CI: 1.42-1.80,
      P<0.001) and 2.53 (95% CI: 1.94-3.31, P<0.001). CONCLUSIONS: This study found
      that patients who were offered an informed choice for screening had higher
      adherence rates than patients who were not offered a choice in real-life
      practices, suggesting that providing screening test options for CRC screening is
      preferred.

PMID- 24935275
TI  - Effect of antidepressants and psychological therapies, including hypnotherapy, in
      irritable bowel syndrome: systematic review and meta-analysis.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional
      gastrointestinal disorder. Evidence relating to the treatment of this condition
      with antidepressants and psychological therapies continues to accumulate.
      METHODS: We performed an updated systematic review and meta-analysis of
      randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled
      Trials Register were searched (up to December 2013). Trials recruiting adults
      with IBS, which compared antidepressants with placebo, or psychological therapies
      with control therapy or "usual management," were eligible. Dichotomous symptom
      data were pooled to obtain a relative risk (RR) of remaining symptomatic after
      therapy, with a 95% confidence interval (CI). RESULTS: The search strategy
      identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty
      one compared psychological therapies with control therapy or "usual management,"
      sixteen compared antidepressants with placebo, and one compared both
      psychological therapy and antidepressants with placebo. Ten of the trials of
      psychological therapies, and four of the RCTs of antidepressants, had been
      published since our previous meta-analysis. The RR of IBS symptom not improving
      with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar
      treatment effects for both tricyclic antidepressants and selective serotonin
      reuptake inhibitors. The RR of symptoms not improving with psychological
      therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy,
      hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy
      were all beneficial. CONCLUSIONS: Antidepressants and some psychological
      therapies are effective treatments for IBS. Despite the considerable number of
      studies published in the intervening 5 years since we last examined this issue,
      the overall summary estimates of treatment effect have remained remarkably
      stable.

PMID- 24935276
TI  - Transarterial chemoembolization vs. radiofrequency ablation for the treatment of
      single hepatocellular carcinoma 2 cm or smaller.
AB  - OBJECTIVES: To compare the effectiveness of transarterial chemoembolization
      (TACE) and radiofrequency ablation (RFA) for treating small (<=2 cm)
      hepatocellular carcinomas (HCCs). METHODS: This retrospective study consisted of
      287 patients (mean age, 57.1 years; age range, 29-84 years; 221 men, 66 women;
      73.5% with HBV; 100% with liver cirrhosis) with Barcelona Clinic Liver Cancer
      very early-stage HCC (<=2 cm single HCC) who were initially treated with TACE
      (n=122) or RFA (n=165). The primary study end point was overall patient survival.
      Secondary study end points were time to progression and tumor response. RESULTS:
      The RFA and TACE groups were well balanced in terms of baseline variables. The
      two groups did not differ significantly in overall survival (P=0.079) or major
      complication (P>0.999) rates. The respective cumulative survival rates at 1, 3,
      5, and 8 years were 97.6, 86.7, 74.5, and 60.0% for RFA and 93.4, 75.4, 63.1, and
      51.1% for TACE. Their objective tumor regression (complete or partial response)
      rates were 100% (165/165) and 95.9% (117/122), respectively (P=0.013). The median
      times to progression for RFA and TACE were 27.0+/-3.8 (95% confidence intervals
      (CIs): 19.6-34.4) and 18.0+/-2.9 (95% CIs: 12.2-23.8) months, respectively. RFA
      yielded a significantly longer time to progression (P=0.034). CONCLUSIONS: TACE
      may be a viable alternative treatment for <=2 cm HCCs when RFA is not feasible.

PMID- 24935277
TI  - Complementary and alternative medicine therapies as symptom management strategies
      for the late effects of breast cancer treatment.
AB  - Advancements in breast cancer treatment continue to improve the likelihood of
      survival. The increase in survival has come at a cost, however; the late effects
      of breast cancer treatment have remained a constant reminder to women of what
      they have endured and require holistic nursing's attention. One area of nursing
      practice that might improve the condition of breast cancer survivors once their
      treatment has ended is complementary and alternative medicine (CAM) therapies. To
      provide guidance to nurses working with breast cancer survivors, a focused review
      of the literature exploring the symptomatology and prevalence of breast cancer's
      late effects as well as the use of CAM therapies to improve those effects is
      presented. Evidence suggests that CAM therapies have sometimes been incorporated
      into symptom management strategies currently employed; however, the evidential
      claims as a whole have been generally inconclusive, especially for complete
      resolution of the late effects. Regardless, a number of studies demonstrate a
      reduction of negative symptoms experienced with few to no side effects of CAM
      therapies. 

PMID- 24935274
TI  - Progress and opportunities in molecular pathological epidemiology of colorectal
      premalignant lesions.
AB  - Molecular pathological epidemiology (MPE) is an integrative molecular and
      population health science that addresses the molecular pathogenesis and
      heterogeneity of disease processes. The MPE of colonic and rectal premalignant
      lesions (including hyperplastic polyps, tubular adenomas, tubulovillous adenomas,
      villous adenomas, traditional serrated adenomas, sessile serrated
      adenomas/sessile serrated polyps, and hamartomatous polyps) can provide unique
      opportunities for examining the influence of diet, lifestyle, and environmental
      exposures on specific pathways of carcinogenesis. Colorectal neoplasia can
      provide a practical model by which both malignant epithelial tumor (carcinoma)
      and its precursor are subjected to molecular pathological analyses. KRAS, BRAF,
      and PIK3CA oncogene mutations, microsatellite instability, CpG island methylator
      phenotype, and LINE-1 methylation are commonly examined tumor biomarkers. Future
      opportunities include interrogation of comprehensive genomic, epigenomic, or
      panomic datasets, and the adoption of in vivo pathology techniques. Considering
      the colorectal continuum hypothesis and emerging roles of gut microbiota and host
      immunity in tumorigenesis, detailed information on tumor location is important.
      There are unique strengths and caveats, especially with regard to case
      ascertainment by colonoscopy. The MPE of colorectal premalignant lesions can
      identify etiologic exposures associated with neoplastic initiation and
      progression, help us better understand colorectal carcinogenesis, and facilitate
      personalized prevention, screening, and therapy. 

PMID- 24935278
TI  - Ethical issues relating to renal transplantation from prediabetic living donor.
AB  - BACKGROUND: In Mexico, diabetes mellitus is the main cause of end - stage kidney
      disease, and some patients may be transplant candidates. Organ supply is limited
      because of cultural issues. And, there is a lack of standardized clinical
      guidelines regarding organ donation. These issues highlight the tension
      surrounding the fact that living donors are being selected despite being
      prediabetic. This article presents, examines and discusses using the principles
      of non-maleficience, autonomy, justice and the constitutionally guaranteed right
      to health, the ethical considerations that arise from considering a prediabetic
      person as a potential kidney donor. DISCUSSION: Diabetes is an absolute
      contraindication for donating a kidney. However, the transplant protocols most
      frequently used in Mexico do not consider prediabetes as exclusion criteria. In
      prediabetic persons there are well known metabolic alterations that may
      compromise the long - term outcomes of the transplant if such donors are
      accepted. Even so, many of them are finally included because there are not enough
      donor candidates. Both, families and hospitals face the need to rapidly accept
      prediabetic donors before the clinical conditions of the recipient and the
      evolution of the disease exclude him/her as a transplant candidate; however, when
      using a kidney potentially damaged by prediabetes, neither the donor's nor the
      recipient's long term health is usually considered.Considering the ethical
      implication as well as the clinical and epidemiological evidence, we conclude
      that prediabetic persons are not suitable candidates for kidney donation. This
      recommendation should be taken into consideration by Mexican health institutions
      who should rewrite their transplant protocols. SUMMARY: We argue that the
      decision to use a kidney from a living donor known to be pre-diabetic or from
      those persons with family history of T2DM, obesity, hypertension, or renal
      failure, should be considered unethical in Mexico if the donor bases the decision
      to donate on socially acceptable norms rather than informed consent as understood
      in modern medicine.

PMID- 24935279
TI  - Climatic adaptation and ecological divergence between two closely related pine
      species in Southeast China.
AB  - Climate is one of the most important drivers for adaptive evolution in forest
      trees. Climatic selection contributes greatly to local adaptation and
      intraspecific differentiation, but this kind of selection could also have
      promoted interspecific divergence through ecological speciation. To test this
      hypothesis, we examined intra- and interspecific genetic variation at 25 climate
      related candidate genes and 12 reference loci in two closely related pine
      species, Pinus massoniana Lamb. and Pinus hwangshanensis Hisa, using population
      genetic and landscape genetic approaches. These two species occur in Southeast
      China but have contrasting ecological preferences in terms of several
      environmental variables, notably altitude, although hybrids form where their
      distributions overlap. One or more robust tests detected signals of recent and/or
      ancient selection at two-thirds (17) of the 25 candidate genes, at varying
      evolutionary timescales, but only three of the 12 reference loci. The signals of
      recent selection were species specific, but signals of ancient selection were
      mostly shared by the two species likely because of the shared evolutionary
      history. FST outlier analysis identified six SNPs in five climate-related
      candidate genes under divergent selection between the two species. In addition, a
      total of 24 candidate SNPs representing nine candidate genes showed significant
      correlation with altitudinal divergence in the two species based on the
      covariance matrix of population history derived from reference SNPs. Genetic
      differentiation between these two species was higher at the candidate genes than
      at the reference loci. Moreover, analysis using the isolation-with-migration
      model indicated that gene flow between the species has been more restricted for
      climate-related candidate genes than the reference loci, in both directions.
      Taken together, our results suggest that species-specific and divergent climatic
      selection at the candidate genes might have counteracted interspecific gene flow
      and played a key role in the ecological divergence of these two closely related
      pine species. 

PMID- 24935280
TI  - A meta-analysis of the effects of nutrient enrichment on litter decomposition in
      streams.
AB  - The trophic state of many streams is likely to deteriorate in the future due to
      the continuing increase in human-induced nutrient availability. Therefore, it is
      of fundamental importance to understand how nutrient enrichment affects plant
      litter decomposition, a key ecosystem-level process in forest streams. Here, we
      present a meta-analysis of 99 studies published between 1970 and 2012 that
      reported the effects of nutrient enrichment on litter decomposition in running
      waters. When considering the entire database, which consisted of 840 case
      studies, nutrient enrichment stimulated litter decomposition rate by
      approximately 50%. The stimulation was higher when the background nutrient
      concentrations were low and the magnitude of the nutrient enrichment was high,
      suggesting that oligotrophic streams are most vulnerable to nutrient enrichment.
      The magnitude of the nutrient-enrichment effect on litter decomposition was
      higher in the laboratory than in the field experiments, suggesting that
      laboratory experiments overestimate the effect and their results should be
      interpreted with caution. Among field experiments, effects of nutrient enrichment
      were smaller in the correlative than in the manipulative experiments since in the
      former the effects of nutrient enrichment on litter decomposition were likely
      confounded by other environmental factors, e.g. pollutants other than nutrients
      commonly found in streams impacted by human activity. However, primary studies
      addressing the effect of multiple stressors on litter decomposition are still few
      and thus it was not possible to consider the interaction between factors in this
      review. In field manipulative experiments, the effect of nutrient enrichment on
      litter decomposition depended on the scale at which the nutrients were added:
      stream reach > streamside channel > litter bag. This may have resulted from a
      more uniform and continuous exposure of microbes and detritivores to nutrient
      enrichment at the stream-reach scale. By contrast, nutrient enrichment at the
      litter-bag scale, often by using diffusing substrates, does not provide uniform
      controllable nutrient release at either temporal or spatial scales, suggesting
      that this approach should be abandoned. In field manipulative experiments, the
      addition of both nitrogen (N) and phosphorus (P) resulted in stronger stimulation
      of litter decomposition than the addition of N or P alone, suggesting that there
      might be nutrient co-limitation of decomposition in streams. The magnitude of the
      nutrient-enrichment effect on litter decomposition was higher for wood than for
      leaves, and for low-quality than for high-quality leaves. The effect of nutrient
      enrichment on litter decomposition may also depend on climate. The tendency for
      larger effect size in colder regions suggests that patterns of biogeography of
      invertebrate decomposers may be modulating the effect of nutrient enrichment on
      litter decomposition. Although studies in temperate environments were
      overrepresented in our database, our meta-analysis suggests that the effect of
      nutrient enrichment might be strongest in cold oligotrophic streams that depend
      on low-quality plant litter inputs. 

PMID- 24935281
TI  - Post-cataract prevention of inflammation and macular edema by steroid and
      nonsteroidal anti-inflammatory eye drops: a systematic review.
AB  - PURPOSE: Favorable outcome after cataract surgery depends on proper control of
      the inflammatory response induced by cataract surgery. Pseudophakic cystoid
      macular edema is an important cause of visual decline after uncomplicated
      cataract surgery. DESIGN: We compared the efficacy of topical steroids with
      topical nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling inflammation
      and preventing pseudophakic cystoid macular edema (PCME) after uncomplicated
      cataract surgery. PARTICIPANTS: Patients undergoing uncomplicated surgery for age
      related cataract. METHODS: We performed a systematic literature search in
      Medline, CINAHL, Cochrane, and EMBASE databases to identify randomized trials
      published from 1996 onward comparing topical steroids with topical NSAIDs in
      controlling inflammation and preventing PCME in patients undergoing
      phacoemulsification with posterior chamber intraocular lens implantation for age
      related cataract. MAIN OUTCOME MEASURES: Postoperative inflammation and
      pseudophakic cystoid macular edema. RESULTS: Fifteen randomized trials were
      identified. Postoperative inflammation was less in patients randomized to NSAIDs.
      The prevalence of PCME was significantly higher in the steroid group than in the
      NSAID group: 3.8% versus 25.3% of patients, risk ratio 5.35 (95% confidence
      interval, 2.94-9.76). There was no statistically significant difference in the
      number of adverse events in the 2 treatment groups. CONCLUSIONS: We found low to
      moderate quality of evidence that topical NSAIDs are more effective in
      controlling postoperative inflammation after cataract surgery. We found high
      quality evidence that topical NSAIDs are more effective than topical steroids in
      preventing PCME. The use of topical NSAIDs was not associated with an increased
      events. We recommend using topical NSAIDs to prevent inflammation and PCME after
      routine cataract surgery.

PMID- 24935283
TI  - In vivo imaging of radial keratoneuritis in patients with Acanthamoeba keratitis
      by anterior-segment optical coherence tomography.
AB  - PURPOSE: To investigate in vivo corneal changes of radial keratoneuritis in early
      stage Acanthamoeba keratitis (AK) using anterior-segment optical coherence
      tomography (AS-OCT). DESIGN: Single-center, prospective clinical study.
      PARTICIPANTS: Four eyes (4 patients with a mean age of 28.5 years) with early
      stage AK showing radial keratoneuritis were included in this study. Definitive
      diagnosis was made by confirmation of AK cysts using in vivo confocal microscopy
      and culture. METHODS: Anterior-segment OCT examination was performed on the
      initial visit and at follow-up visits paying special attention to radial
      keratoneuritis. MAIN OUTCOME MEASURES: Selected AS-OCT images of the cornea were
      evaluated qualitatively for the shape and degree of light reflection of abnormal
      neurons. RESULTS: With the use of AS-OCT, we successfully obtained high
      resolution images of putative radial keratoneuritis in all patients as highly
      reflective bands or lines in the corneal stroma. The depth and width of the
      highly reflective bands/lines varied from case to case (anterior stroma to mid
      stroma, from 20 to 200 MUm). Some lines ran obliquely from the deep peripheral
      stroma toward the anterior stroma, and some were located at different depths
      (subepithelial and mid-stroma) and ran relatively parallel to the corneal layers.
      After appropriate treatment, radial keratoneuritis was resolved by both slit-lamp
      biomicroscopy and AS-OCT in all patients. CONCLUSIONS: High-resolution Fourier
      domain AS-OCT provides novel and detailed visual information of radial
      keratoneuritis in patients with early-stage AK. Visualization of radial
      keratoneuritis by AS-OCT may be a useful adjunct to the diagnosis and follow-up
      of early-stage AK.

PMID- 24935284
TI  - Glaucoma diagnostic accuracy of optical coherence tomography parameters in early
      glaucoma with different types of optic disc damage.
AB  - PURPOSE: To compare the initial visual field (VF) defect pattern and the spectral
      domain optical coherence tomography (OCT) parameters and investigate the effects
      of distinct types of optic disc damage on the diagnostic performance of these OCT
      parameters in early glaucoma. DESIGN: Retrospective, observational study.
      PARTICIPANTS: A total of 138 control eyes and 160 eyes with early glaucoma were
      enrolled. The glaucomatous eyes were subdivided into 4 groups according to the
      type of optic disc damage: focal ischemic (FI) group, myopic (MY) group, senile
      sclerotic (SS) group, and generalized enlargement (GE) group. METHODS: The values
      of total deviation (TD) maps were analyzed, and superior-inferior (S-I)
      differences of TD were calculated. The optic nerve head (ONH) parameters,
      peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell-inner
      plexiform layer (GCIPL) thicknesses were measured. MAIN OUTCOME MEASURES:
      Comparison of diagnostic ability using area under the receiver operating
      characteristic curves (AUCs). RESULTS: The S-I and central S-I difference of the
      FI group were larger than those of the GE group. The rim area of the SS group was
      larger than those of the 3 other groups, and the vertical cup-to-disc ratio (CDR)
      of the GE group was larger than that of the MY group. In addition, the minimum
      and inferotemporal GCIPL thicknesses of the FI group were smaller than those of
      the GE group. The AUC of the rim area (0.89) was lower than that of the minimum
      GCIPL (0.99) in the SS group, and the AUC of the vertical CDR (0.90) was lower
      than that of the minimum GCIPL (0.99) in the MY group. Furthermore, the AUCs of
      the minimum GCIPL thicknesses of the FI and MY group were greater than those of
      the average pRNFL thickness for detecting glaucoma, as opposed to the SS and GE.
      CONCLUSIONS: The OCT parameters differed among the 4 groups on the basis of the
      distinct optic disc appearance and initial glaucomatous damage pattern.
      Clinicians should be aware that the diagnostic capability of OCT parameters could
      differ according to the type of optic disc damage in early glaucoma.

PMID- 24935285
TI  - The medical reformation.

PMID- 24935282
TI  - Sustained delivery fluocinolone acetonide vitreous implants: long-term benefit in
      patients with chronic diabetic macular edema.
AB  - PURPOSE: To present the safety and efficacy of intravitreal implants releasing
      0.2 MUg/day fluocinolone acetonide (FAc) in patients with chronic versus
      nonchronic diabetic macular edema (DME). To assess ocular characteristics,
      anatomic changes, and re-treatment and ancillary therapies that may explain the
      differential treatment effect seen with intravitreal implants releasing FAc 0.2
      MUg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk
      assessment for the FAc 0.2-MUg/day and FAc 0.5-MUg/day doses has been reported
      previously. DESIGN: Preplanned subgroup analysis of chronic (duration of
      diagnosis, >=3 years) and nonchronic (duration of diagnosis, <3 years) DME in
      patients from 2 randomized, sham injection-controlled, double-masked, multicenter
      clinical trials. PARTICIPANTS: Patients with persistent DME despite 1 or more
      macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc
      0.2 MUg/day (n = 375), or FAc 0.5 MUg/day (n = 393). METHODS: Patients received
      study drug or sham injection and after 6 weeks were eligible for rescue laser.
      Based on re-treatment criteria, additional masked study drug could be given after
      1 year. MAIN OUTCOME MEASURES: Percentage of patients with improvement of 15
      letters or more from baseline. Secondary outcomes included other parameters of
      visual function and foveal thickness. RESULTS: At month 36, the difference
      between FAc 0.2 MUg/day and sham control in the percentage of patients who gained
      15 letters or more was significantly greater in chronic DME patients (FAc 0.2
      MUg/day, 34.0% vs. sham, 13.4%; P<0.001), compared with patients with nonchronic
      DME (FAc 0.2 MUg/day, 22.3% vs. sham, 27.8%; P = 0.275). The greater response in
      patients with chronic DME was not associated with baseline ocular
      characteristics, changes in anatomic features, or differences in re-treatment or
      ancillary therapies. The ocular adverse event profile for FAc 0.2 MUg/day was
      similar regardless of DME duration. CONCLUSIONS: This is the first published
      analysis correlating duration of diagnosis of DME with treatment effect. In
      patients with chronic DME, FAc 0.2 MUg/day provides substantial visual benefit
      for up to 3 years and would provide an option for patients who do not respond to
      other therapy.

PMID- 24935287
TI  - Wojciech Rowinski, a humanist and transplant surgeon, played a seminal role to
      establish the government-run national transplantation program in Poland.

PMID- 24935286
TI  - Why and how to spare the hippocampus during brain radiotherapy: the developing
      role of hippocampal avoidance in cranial radiotherapy.
AB  - The goal of this review is to summarize the rationale for and feasibility of
      hippocampal sparing techniques during brain irradiation. Radiotherapy is the most
      effective non-surgical treatment of brain tumors and with the improvement in
      overall survival for these patients over the last few decades, there is an effort
      to minimize potential adverse effects leading to possible worsening in quality of
      life, especially worsening of neurocognitive function. The hippocampus and
      associated limbic system have long been known to be important in memory formation
      and pre-clinical models show loss of hippocampal stem cells with radiation as
      well as changes in architecture and function of mature neurons. Cognitive
      outcomes in clinical studies are beginning to provide evidence of cognitive
      effects associated with hippocampal dose and the cognitive benefits of
      hippocampal sparing. Numerous feasibility planning studies support the
      feasibility of using modern radiotherapy systems for hippocampal sparing during
      brain irradiation. Although results of the ongoing phase II and phase III studies
      are needed to confirm the benefit of hippocampal sparing brain radiotherapy on
      neurocognitive function, it is now technically and dosimetrically feasible to
      create hippocampal sparing treatment plans with appropriate irradiation of target
      volumes. The purpose of this review is to provide a brief overview of studies
      that provide a rationale for hippocampal avoidance and provide summary of
      published feasibility studies in order to help clinicians prepare for clinical
      usage of these complex and challenging techniques. 

PMID- 24935288
TI  - The certification of transplant coordinators in Europe.
AB  - The appropriate clinical management of the integrated process of Donation and
      Transplantation implies the participation of the Transplant Coordinator. The aim
      of this article is to present the process of Certification of Transplant
      Coordinators in Europe since 2001, in accordance with the Council of Europe
      Recommendations and the evolving model implemented in 2008 under the auspices of
      the UEMS, reporting the longest running European standardized assessment of
      Transplant Coordination skills and knowledge. It includes the rationale for
      development of a certification process, how the examinations were developed and
      updated, eligibility to take the examination, and relationship with standards of
      practice for Transplant Coordinators. A total of 455 healthcare professionals
      were certified in two phases: 1(st) ETCO certification since 2001 to 2007 (390)
      and 2(nd) ETCO/UEMS certification from 2008 to 2011 (65). 

PMID- 24935289
TI  - Effects of an in-house coordinator and practitioner referral rather than proxy
      referral on tissue donation rates.
AB  - INTRODUCTION: Timely referral of patients following asystolic death to an organ
      procurement organization (OPO) may increase tissue donation rates. Lack of
      education of health care providers and nonphysicians (admitting department) about
      timely referral to the OPO following asystolic death may adversely affect tissue
      donation rates. We hypothesized that using an in-house donation coordinator for
      provider education and changing the responsibility for calling the OPO from the
      admitting department to the licensed independent practitioner (LIP) declaring
      death would increase timely referral and tissue donation rates. METHODS: An
      education program was developed in 2005 by a newly hired in-house coordinator to
      highlight the importance of tissue donation. In addition, to improve timely
      referrals to the OPO after death, the instructions accompanying the working copy
      of the death certificate were altered to require the patient's LIP to call the
      OPO within 1 hour of death (early 2007). Rates for both timely referrals and
      tissue donors were modeled by a Poisson regression model with a log link
      function. RESULTS: Timely referral rates rose from 48% before the interventions
      to 72% after the intervention (P < .0001). The number of tissue donors per number
      of referrals also increased significantly (P = .025) over that period.
      CONCLUSIONS: An in-house donation coordinator initiated education program and LIP
      referral rather than referral by other parties following asystolic death results
      in higher tissue donation rates.

PMID- 24935290
TI  - Bench surgery with renal autotransplantation for angiomyolipoma of renal sinus.
AB  - BACKGROUND: The treatment of angiomyolipomas (AML) of the renal sinus is
      challenging and often requires nephrectomy. In this study, we report on 5
      patients who underwent extracorporeal AML resection and subsequent renal
      autotransplantation (RA) for renal sinus AML. METHODS: As of May 2013, 5 patients
      had undergone extracorporeal AML resection and RA for renal sinus AML at our
      institute. Separation of the AML in renal sinus is performed by combined sharp
      and blunt dissection. Tissue between AML and renal sinus is ligated where blood
      vessels cannot be excluded. When complicated with AML of the renal parenchyma,
      the AMLs were resected using ultrasound guidance. RESULTS: Renal nuclear scan
      showed that kidney grafts were perfused uniformly without evidence of segmental
      infarction at day 7 posttransplantation in all patients. No significant
      deterioration in renal function and tumor recurrence was noted over a median
      follow-up of 3 months (range: 1 to 6 months). All patients presented with normal
      blood pressure values. No intraoperative complications occurred. CONCLUSIONS:
      Bench surgery and subsequent RA method, due to its advantage of kidney
      preservation, is a valuable option for renal sinus AML treatment.

PMID- 24935291
TI  - The minimal-access kidney transplantation technique in living-donor
      transplantation: results from a retrospective analysis.
AB  - OBJECTIVES: During the last 15 years, there was tremendous progress in minimally
      invasive surgery and minimal-access surgery. Many conventional surgical
      procedures were replaced by these techniques, resulting in a wide range of
      benefits for the patients. In kidney transplantation, many centers choose an
      approach to the iliac fossa through an oblique or J-shaped incision. This might
      have possible disadvantages due to the extent of tissue trauma. Thus, we
      introduced a minimal-access kidney transplantation technique (MAKT) as a
      transplantation method in our center. We retrospectively analyzed this technique
      used for 11 living-donor kidney transplants and report here our experience.
      PATIENTS AND METHODS: From April 2008 to July 2011, 11 living-donor kidney
      recipients were subjected to the MAKT and were matched (age, sex) with a
      historical group from our center from 2000 to 2007. To analyze the assumption of
      noninferiority of the MAKT in comparison to the standard approach, a matched case
      control study design was chosen, with creatinine level at 1 year after
      transplantation as the primary outcome variable. We used a Wilcoxon signed rank
      test; 1-sided significance level was 2.5%. RESULTS: Eleven recipients were
      included. Both groups were almost similar regarding age and body mass index.
      Characteristics of the procedure were significantly different only for cold
      ischemic time (114 minutes MAKT vs 77 minutes historical group). In the MAKT
      group, there were no reinterventions necessary, no wound infections, no
      incisional hernia, no acute rejection episodes, no graft losses, and 2
      lymphoceles occurred. Further, no urinary leakage or ureteral stenosis and no
      vascular complications were observed. The statistical analysis of the primary
      endpoint revealed a noninferiority of the MAKT technique (P = .0005).
      CONCLUSIONS: Considering the fact that this is an initial series and a
      retrospective analysis, the applied MAKT technique seems to be safe in terms of
      both graft function after 1 year and surgical complications.

PMID- 24935292
TI  - Translation, cultural adaptation and validation of the kidney disease quality of
      life-short form 1.3 in an African country.
AB  - BACKGROUND: The impact of dialysis on patient quality of life has been recognized
      as an important outcome measure. The Dialysis Outcomes and Practice Patterns
      Study compared quality of life in 4 continents [1], but very scarce information
      is available about dialysis patients' quality of life in Africa. The objective of
      this study was to translate the Kidney Disease Quality of Life-Short Form (KDQOL
      SF) into Moroccan and measure its psychometric properties. METHODS: The
      questionnaire was first translated into Moroccan by 2 independent translators,
      and then 2 backward translations into English were performed after pretesting in
      10 dialysis patients. The final questionnaire was then administered to 80
      dialysis patients. Reliability was estimated by internal consistency and test
      retest reliability. Validity was assessed using known group comparisons and
      correlations between overall health rating and scales scores. RESULTS: Some
      activities were substituted since they were not common in Morocco. All subscales
      had a Cronbach alpha above the recommended value except for 3 scales. All of the
      items showed good test-retest reliability. Correlation of items within subscales
      was higher than that of items outside subscales in 87% of cases. Regarding
      construct validity, all KDQOL-SF scales had significant correlation with overall
      health rating except for sexual function and dialysis staff encouragement.
      Furthermore, the questionnaire could be used to discriminate between subgroups of
      the patients. CONCLUSIONS: The psychometric properties of the KDQOL-SF resulting
      from this first-time administration of the instrument support the validity and
      reliability of the KDQOL-SF as a measure of quality of life of patients having
      hemodialysis in Morocco.

PMID- 24935293
TI  - Calcineurin inhibitor avoidance and withdrawal for kidney transplantation: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Many studies have compared the safety and efficacy of the calcineurin
      inhibitor (CNI) avoidance or CNI withdrawal regimens with typical CNI regimens,
      but the results remain controversial. The aim of this systematic review and meta
      analysis is to make a profound review and an objective appraisal of the safety
      and efficacy of the CNI avoidance and CNI withdrawal protocols. METHODS: We
      searched PUBMED, EMBASE, and the reference lists of retrieved studies to identify
      randomized controlled trials (RCTs) that referred to CNI-free regimens, CNI
      avoidance, or CNI withdrawal for kidney transplantation. Eight publications
      involving 27 different RCTs and a total of 3953 patients were used in the
      analysis. RESULTS: Use of mammalian target of rapamycin inhibitors, namely
      sirolimus (SRL), in combination with mycophenolate, conserve graft function at 1
      year (glomerular filtration rage [GFR]: mean difference MD 6.21, 95% CI 0.02
      12.41, P = .05; serum creatinine: MD -0.11, 95% CI -0.19 to -0.03, P = .01,
      respectively) and 2 years post-transplant (GFR: MD 13.96, 95% CI 7.32-20.60, P <
      .0001). Similarly, early withdrawal (<= 6 months) of CNIs protect graft function
      at 1 year after transplant (GFR: MD 7.03, 95% CI 4.84-9.23, P < .00001, serum
      creatinine: MD -0.21, 95% CI -0.22 to -0.19, P < .00001, respectively). CNI
      avoidance and withdrawal strategies are associated with higher incidence of acute
      rejection at 1 year post-transplant (odds ratio OR 1.74, 95% CI 1.08-2.81, P =
      .02; OR 1.78, 95% CI 1.35-2.34, P < .0001, respectively). At 2 years after
      transplant, there was no significant difference (OR 0.92, 95% CI 0.33-2.51, P =
      .86; OR 2.42, 95% CI 1.01-5.82, P = .05, respectively). Meanwhile, neither
      adverse events nor patient/graft survival differed significantly between the CNI
      free and CNI protocols at 1 and 2 years. Referring to long-term results in the
      published RCTs, use of CNI-free and CNI withdrawal regimens achieve better renal
      function vs CNI regimens, with no significant difference in patient and graft
      survival, acute rejection, and most reported adverse events. CONCLUSIONS: In
      conclusion, this systematic review and meta-analysis suggests that renal
      recipients with early withdrawal of CNI drugs or avoiding CNI with SRL perform
      better to conserve graft function at 1 and 2 years post-transplant. Though the
      use of CNI regimens performs no better in 2-year acute rejection vs the contrast
      group, they greatly decrease the incidence of acute rejection at the first year
      after transplantation. CNI avoidance and withdrawal regimens improve the long
      term renal function and perform similarly in the acute rejection, patient and
      graft survival, and adverse events. Due to the limited amounts of long-term
      studies, more high-quality RCTs are needed.

PMID- 24935295
TI  - Effect of rapamycin on spleen size in longstanding renal transplant recipients.
AB  - BACKGROUND: Based on evidence available in the literature, rapamycin, a mammalian
      target of rapamycin (mTOR) inhibitor, but not calcineurin inhibitors (CNIs), has
      been shown to decrease spleen size. Small spleen, in some instances, is
      associated with hyposplenism, a condition recently reported in patients with
      longstanding renal transplant. Accordingly, the effect of immunosuppressive drugs
      on spleen size was evaluated. METHODS: Renal transplant recipients (35 taking
      mTOR and 68 CNI) were included, in whom a standardized investigation of the
      kidney allograft and spleen with the use of color Doppler ultrasound was
      performed and a peripheral smear were reviewed for the presence of Howell-Jolly
      bodies (HJBs). RESULTS: We enrolled 103 patients (64 men; 66 from a deceased
      donor). The mean age was 47.7 years (range, 23.0-74.0 y). Mean transplant
      duration was 1,899 days (range, 181-6,883 d). According to the presence of HJBs,
      the prevalence of hyposplenism was 47.6% for the entire cohort. The differences
      between the mTOR and CNI groups regarding sex and the presence of HJBs were not
      statistically significant (P > .05). Age, creatinine, hemoglobin, leukocytes,
      platelets, and Doppler parameters in spleen and kidney were similar in both
      groups (P > .05). mTOR patients had a decreased spleen length size (90.09 +/-
      13.02 mm vs 111.95 +/- 18.66 mm; P < .001), a longer transplant duration (3,576
      +/- 1,594 d vs 1,036 +/- 1,369 d; P < .001) and higher serum cholesterol (227.50
      +/- 38.75 mg/dL vs 182.67 +/- 37.74 mg/dL; P < .001) and triglycerides (194.23 +/
      79.88 mg/dL vs 148.70 +/- 55.54 mg/dL; P = .003) levels compared with the CNI
      group. A multivariate analysis showed mTOR inhibitor to be the most important
      predictor of spleen size. In both the mTOR and CNI groups, the comparison between
      the subgroups of present and absent HJBs did not show any difference.
      CONCLUSIONS: The findings of this study suggest that small spleens in transplant
      recipients may be linked to treatment with an mTOR inhibitor, although this
      apparently does not compromise splenic function.

PMID- 24935294
TI  - Pharmacokinetics of everolimus when combined with cyclosporine in Japanese de
      novo renal transplant recipients.
AB  - BACKGROUND: Currently, there are no published data on pharmacokinetics (PK) of
      everolimus in combination with cyclosporine in Japanese renal transplant
      patients. We evaluated the PK of everolimus in Japanese de novo renal transplant
      patients who received everolimus in combination with cyclosporine. METHODS: In
      this phase 3, multicenter, randomized, open-label study, patients were randomized
      (1:1) to 1 of the 2 groups: everolimus 1.5 mg (targeted C0 of 3-8 ng/mL) plus
      reduced-dose cyclosporine or mycophenolate mofetil 2 g/d plus standard-dose
      cyclosporine. PK assessments for everolimus were performed on day 28 (month 1) in
      the PK subpopulation. RESULTS: A total of 11 patients (7 men), mean age 47.5 +/-
      11.21 years, were enrolled for PK analysis of everolimus. Starting at 1.5 mg
      (0.75 mg twice a day), the mean dose over a period of 28 days was 0.705 +/-
      0.1011 mg. Everolimus mean trough concentration was 4.307 +/- 1.2459 ng/mL and
      mean peak concentration was 13.539 +/- 3.5330 ng/mL, which peaked at 1 to 2 hours
      postdose. The average concentration was 7.558 +/- 1.4723 ng/mL, area under the
      concentration-time curve was 90.70 +/- 17.667 ng.h/mL, and peak-trough
      fluctuation was 122.6%. The PK parameters of everolimus were comparable to those
      in the earlier phase 3 studies (A2306 and A2307). The mean everolimus trough
      levels were within the target ranges at all time points ranging from 3.4 to 5.5
      ng/mL (everolimus 0.75 mg twice a day, safety population). The majority of
      patients (>85% from day 7 onward) were maintained within the targeted everolimus
      trough blood levels (safety population). These data were similar to a non
      Japanese study (A2309). CONCLUSIONS: The pharmacokinetic characteristics of
      everolimus in Japanese de novo renal transplant patients did not differ from
      those previously observed in non-Japanese patients, hence the same dosage of
      everolimus may be acceptable in Japanese patients.

PMID- 24935296
TI  - Determining renal resistive and pulsatility indexes long-term after kidney
      transplantation in kidney transplant recipients on cyclosporine a-, tacrolimus-,
      or sirolimus-based regimens.
AB  - BACKGROUND: Renal Doppler ultrasound intrarenal resistive index (RI) and
      pulsatility index (PI) are 2 noninvasive Doppler ultrasonographic markers to
      determine kidney allograft function, and have been used mainly for diagnosing
      allograft dysfunction during early posttransplantation periods. Little is known
      about the stability of RI and PI in allograft recipients receiving cyclosporine A
      (CyA)-, tacrolimus (TAC)-, or sirolimus (SRL)-based immunosuppressive regimens
      long-term after kidney transplantation. METHODS: This study assessed RI and PI by
      Doppler ultrasonography in 155 kidney allograft recipients between July 2012 and
      March 2013. The period from kidney transplantation to performance of allograft
      Doppler ultrasound was between 23 and 231 months in the TAC group (n = 75), 21
      and 261 months in the CyA group (n = 25), and 21 and 210 months in the SRL group
      (n = 55). RESULTS: Univariate logistic regression analysis revealed no
      correlation between resistance indexes and estimated glomerular filtration rate,
      proteinuria, cholesterol, triglyceride, graft and patient survival, human
      leukocyte antigen mismatches, and creatinine. There was no significant difference
      among the TAC, CyA, and SRL treatment groups in terms of resistance indexes (RI
      and PI) (P = .193 and P = .216, respectively). Univariate logistic regression
      analysis revealed that RI and PI values correlated significantly with the
      recipients' ages (R = 0.375, P < .001), but not with donor age. The results of
      multivariate logistic regression analysis also revealed statistically the
      strongest correlation between recipients' ages and RI (95% confidence interval =
      0.002, R(2) = 20.5%, P < .001) and PI (95% confidence interval = 0.008, R(2) =
      16.2%, P < .001) values. CONCLUSIONS: Intrarenal RI and PI remained stable over
      time in allograft recipients after transplantation, and there was no significant
      difference between calcineurin inhibitor-based and calcineurin inhibitor-free
      immunosuppressive treatment groups. Only recipients' ages showed a positive
      correlation with RI and PI values. Long-term allograft and patient survival were
      both excellent (100%) and associated with RI < 0.75.

PMID- 24935297
TI  - Attitude of hemodialysis patients toward renal transplantation: a Moroccan
      Interregional Survey.
AB  - INTRODUCTION: Kidney transplantation (KT) is considered the treatment of choice
      for many patients with severe chronic kidney disease because quality of life and
      survival are often better than in patients who undergo dialysis. This study
      assessed patients' knowledge and attitudes regarding KT. PATIENTS AND METHODS: A
      total of 2066 hemodialysis patients were investigated as part of the ARTEMIS
      (Attitude Toward Renal Transplantation and Eligibility Among Dialysis Patients in
      a Moroccan Interregional Survey) study. RESULTS: Patients' mean age was 52.9
      years, and the mean duration of hemodialysis was 55.3 months. Among these
      patients, 73.3% would like to undergo transplantation. Among the subjects wishing
      to be transplanted, 75.7% would accept the graft from a living or a cadaveric
      donor; 17.8% would refuse transplantation from a related living donor; and 6.5%
      would reject organs from donors after brain death. Approximately 17% of patients
      have a potential related living donor. The main motivating factor for KT was
      fluid restriction and diet constraints (43.3%). One third of patients believe
      that Islam does not allow organ donation from a related living donor, and almost
      one half think that it is prohibited from a brain-dead donor. Independent factors
      affecting patients' attitude toward KT were young age, male gender, persistence
      of residual diuresis, availability of a related living donor, and better
      information on the subject of transplantation. CONCLUSIONS: To improve
      hemodialysis patients' accessibility to KT, patients, their families, and other
      support providers need better information. Awareness campaigns are needed to
      promote organ donation.

PMID- 24935298
TI  - Management of urologic complications in renal transplantation: a single-center
      experience.
AB  - INTRODUCTION: Ureterovesical complications subsequent to renal transplantation
      are associated with a high morbidity leading to graft loss or even death. In the
      present study, the management of these complications by using interventional and
      surgical procedures (native pyeloureterostomy [NPUS]/ureteroureterostomy [NUU] vs
      ureteroneocystostomy [UNC]) was evaluated retrospectively. PATIENTS AND METHODS:
      Between 1994 and 2012, a total of 780 kidney transplantations (690 deceased and
      90 living donors) were performed at our institution. Demographic, clinical, and
      laboratory data from patients with urologic complications were analyzed and
      compared. RESULTS: Fifty patients (6.4%) exhibited ureterovesical complications,
      and 18 patients (36%) were operated on immediately. In 32 (64%) of 50 patients,
      an interventional procedure was initially performed, with 21 patients (66%)
      undergoing operation due to therapy failure. NPUS/NUU and UNC were performed in
      26 (66.6%) and 13 (33.3%) patients, respectively. Indications for an operation
      were ureteral stenosis in 12 patients (30.8%), ureteral necrosis and urine
      leakage in 19 patients (48.7%), and symptomatic vesicoureteral reflux in 8
      patients (20.5%). Long-term results were comparable between all groups.
      CONCLUSIONS: Surgical revision of ureteral complications should be the standard
      therapy. NPUS/NUU, UNC, and the successful interventional procedures did not
      differ significantly in terms of long-term results.

PMID- 24935299
TI  - Trends of pulmonary embolism before and after kidney transplantation in black
      versus white patients.
AB  - BACKGROUND: Pulmonary embolism (PE) is an important cause of in-hospital
      mortality and is common in renal transplantation and maintenance dialysis
      patients. PE incidence is higher among patients who are black; however,
      differences in trends of incidence and outcomes of PE by race among patients on
      dialysis and after renal transplantation is not well known. METHODS: In this
      observational study, the incidences of PE hospitalizations and mortality were
      studied in those with renal transplant, on maintenance dialysis, and in general
      population. Incidences were compared across racial groups. Renal transplantation
      status as a predictor of mortality was also examined. RESULTS: The incidences of
      PE in general population, dialysis, and renal transplant groups were 70.5, 518.8,
      and 158.8 per 100,000 population, respectively. Incidence was higher in blacks
      across all groups. The age-adjusted incidence of PE admissions increased over
      time in all groups with greater increase in blacks in non-transplant groups (the
      slope in dialysis for blacks was 112.1 versus that for whites at 49.4; P = .001;
      the slope in general population for blacks was 9.3 versus 3.4 for whites; P =
      .003). The mortality rate in general population was not significantly different
      than renal transplant group (3.4% versus 1.9%, P = .2); however, was lower than
      6.8% seen in dialysis group (P < .001). The mortality rate was not different
      between whites and blacks. Maintenance dialysis was an independent predictor of
      mortality (odds ratio [OR] 1.94; 95% confidence interval [CI] 1.62-2.32).
      CONCLUSIONS: PE in those with renal transplant is more common than in general
      population but less common than those on maintenance dialysis. The mortality rate
      for PE hospitalizations is equivocal between renal transplant and general
      population but higher for patients on dialysis. The incidence of PE
      hospitalizations is not only higher among blacks, but is increasing
      disproportionately in this group among those who are on maintenance dialysis and
      within general population.

PMID- 24935300
TI  - A prospective analysis of the effects of enteric-coated mycophenolate sodium and
      mycophenolate mofetil co-medicated with a proton pump inhibitor in kidney
      transplant recipients at a single institute in China.
AB  - BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS) and mycophenolate
      mofetil (MMF), two prodrugs of mycophenolic acid (MPA), have been used in
      immunosuppressive regimens. After being taken orally, both of them transform to
      MPA to achieve immune suppression effects; however, the main site of absorption
      and metabolism of EC-MPS is different from that of MMF in vivo. Therefore,
      combined application with related drugs may result in different MPA levels and
      have different clinical effects in kidney transplant recipients. OBJECTIVE: To
      evaluate the efficacy of EC-MPS compared with MMF in Chinese renal transplant
      patients comedicated with a proton pump inhibitor (PPI). METHODS: Our subjects
      were 88 patients who received renal transplants at the 309th Hospital of the
      Chinese PLA from May 2010 to April 2013. These were made up of two groups
      including 27 patients with EC-MPS and 61 with MMF. The immunosuppression regimen
      was EC-MPS/MMF + cyclosporine/tacrolimus + steroid hormone, comedicated with a
      PPI (omeprazole). The patients' levels of exposure of MPA within 1 week after
      operation were monitored. Clinical indicators such as incidence of delayed graft
      function and acute rejection, the rate of change of serum creatinine hemoglobin,
      leucocytes, and neutrophils, as well as clinical adverse drug reactions and drug
      conversion were analyzed retrospectively. RESULTS AND CONCLUSION: The kidney
      function of patients recovered to normal in both the EC-MPS and MMF groups. The
      mean concentration to peak (Cmax), the mean half-life (t1/2), and the area under
      the concentration-time curve (AUC0-12) of MPA in the EC-MPS group were higher
      than those in the MMF group (P < .05). This indicated that the pharmacokinetic
      parameters for MPA when EC-MPS is co-administered with a PPI in kidney transplant
      patients in China is better than for comedication with MMF and a PPI. The MMF
      group had a higher incidence of drug withdrawal because of higher infection
      rates, leucocyte decrease, and more gastrointestinal side effects than the EC-MPS
      group (P < .05). No significant differences in the clinical effect on kidney
      transplant recipients were observed in the limited observation time.

PMID- 24935301
TI  - Impact of transjugular intrahepatic portosystemic shunt creation on intermediate
      term model for end-stage liver disease score progression.
AB  - PURPOSE: To assess the impact of transjugular intrahepatic portosystemic shunt
      (TIPS) creation on Model for End-stage Liver Disease (MELD) score temporal
      progression in patients with liver cirrhosis. MATERIALS AND METHODS: In this
      single-institution retrospective study, 256 consecutive patients who underwent
      TIPS creation between 1999 and 2013 were identified for potential investigation.
      Inclusion criteria for analysis consisted of at least 6 months of post-TIPS
      clinical follow-up with available lab values at 1, 3, 6, and, if available, 12
      months post-TIPS for MELD score calculation. Patients who were lost to follow-up
      or expired within 6 months, lacked sufficient lab follow-up, or underwent liver
      transplantation within 6 months of TIPS were excluded from the study cohort.
      Within-patient variance in MELD score was assessed using repeated-measures
      analysis of variance. RESULTS: Sixty-six patients met criteria for study
      inclusion. TIPS were created for variceal hemorrhage (n = 26) or ascites,
      hydrothorax, or portal vein thrombosis (n = 40). Hemodynamic success rate was 97%
      (64/66) and median portosystemic pressure gradient reduction was 13 mm Hg. Median
      baseline MELD score was 14 (range 7-26). Low MELD scores (<= 10, n = 16)
      increased in sequential scores over 1-year follow-up (median increase +3.5),
      intermediate MELD scores (11-18, n = 34) showed general stability in successive
      scores over 1-year follow-up (median increase +1), and high MELD scores (>= 19, n
      = 16) decreased in serial scores over 1-year follow-up (median decrease -4);
      these trends are compatible with published MELD progression tendencies in
      cirrhotic patients without TIPS. However, the MELD score changes were not
      statistically significant (P = .172) on within-subject comparison. CONCLUSIONS:
      Among patients with liver cirrhosis who recover from the procedure, TIPS creation
      does not alter the natural MELD score evolution during intermediate term follow
      up, and as such does not significantly alter liver transplant candidacy.

PMID- 24935302
TI  - Tumor existence and tumor size as prognostic factors in hepatitis B virus-related
      cirrhosis patients who underwent liver transplantation.
AB  - BACKGROUND: Hepatitis B virus (HBV)-related chronic liver disease is one of the
      most common indications for liver transplantation (LT). Patient data in our unit
      were collected to evaluate the impact of liver tumor on outcomes in patients with
      HBV-related cirrhosis who underwent LT. METHODS: HBV transplantation patients in
      our hospital from August 2002 to March 2012 were analyzed and compared according
      to LT indications: decompensated cirrhosis (DEC) or hepatocellular carcinoma
      (HCC). For HCC patients, receiver operating characteristic (ROC) curve analysis
      was used to determine the cutoff tumor size for prognosis, namely the maximum
      tumor diameter. According to the cutoff size, patients were divided into 2
      groups: large-size HCC and small-size HCC. The correlations among other
      clinicopathologic factors were also investigated. Potential prognostic factors
      were evaluated with the use of Cox proportional hazards model analysis. RESULTS:
      The 1-, 3-, and 5-year overall survival rates of the 111 HBV-related patients
      were 76.2%, 43.2%, and 32.9%, respectively. Patients with HCC had significantly
      poorer overall survival than those with only DEC (P < .05). The mean tumor size
      was 5.97 cm, and ROC analysis indicated that the cutoff tumor size for prognosis
      was 4.25 cm, with sensitivity and specificity of 62.8% and 81.0%, respectively
      (area under the ROC curve, 0.760; 95% CI, 0.644-0.877; P < .001). According to
      this cutoff point, 31 patients had large tumor size (>= 4.25 cm) and 33 had small
      tumor size (<4.25 cm). Patients with small tumor size had significantly better
      overall survival than those with large tumor size (P < .05). Univariate analysis
      showed that only the tumor size (risk ratio, 1.14; P < .001) was significantly
      associated with the overall survival. CONCLUSIONS: Tumor existence and tumor size
      are prognostic factors in HBV-related cirrhosis. With the use of a tumor size
      cutoff value of 4.25 cm, patients with large-size tumors have significantly
      poorer overall survival than those with small-size tumors.

PMID- 24935303
TI  - Aminocaproic Acid (amicar) as an alternative to aprotinin (trasylol) in liver
      transplantation.
AB  - INTRODUCTION: This study compared clinical outcomes for a large number of liver
      transplant patients receiving intraoperative epsilon-aminocaproic acid (EACA),
      aprotinin, or no antifibrinolytic agent over an 8-year period. PATIENTS AND
      METHODS: Records for deceased donor liver transplants were reviewed. Data
      included antifibrinolytic agent, blood loss, early graft function, and
      postoperative complications. Study groups included low-dose aprotinin, high-dose
      aprotinin, EACA (25 mg/kg, 1-hour infusion), or no antifibrinolytic agent.
      RESULTS: Data were included for 1170 consecutive transplants. Groups included low
      dose aprotinin (n = 324 [28%]), high-dose aprotinin (n = 308 [26%]), EACA (n =
      216 [18%]), or no antifibrinolytic (n = 322 [28%]). EACA had the lowest
      intraoperative blood loss and required the fewest transfusions of plasma.
      Patients receiving no agent required the most blood transfusions. Early graft
      loss was lowest in the EACA group, and 90-day and 1-year patient survival rates
      were significantly higher for the low-dose aprotinin and EACA groups according to
      Cox regression. Complications were similar, but there were more episodes of deep
      vein thrombosis in patients receiving EACA. CONCLUSIONS: These results suggest
      that transitioning from aprotinin to EACA did not result in worse outcomes. In
      addition to decreased intraoperative blood loss, a trend toward improved graft
      and patient survival was seen in patients receiving EACA.

PMID- 24935304
TI  - Left-side hepatectomy in living donors: through a reduced upper-midline incision
      for liver transplantation.
AB  - BACKGROUND: We present our attempts at reducing the length of incision in living
      donor left-side hepatectomy without laparoscopic approach. METHODS: The chief
      surgeon initially made a 10-cm upper midline incision and performed all
      procedures through a minilaparotomy without abdominal wall lifting or
      pneumoperitoneum. For the procedures in the lateral and deep areas, we
      effectively applied traction to the wound in multiple directions using a wound
      retraction system so that the chief surgeon could obtain a good direct view. We
      also placed a fiberscope on the minilaparotomy so that the assistant surgeons
      could obtain an additional video view via a monitor. Surgeons lengthened the
      incision at their own discretion if the initial length was thought to be too
      short for the donor's safety. Since February 2009, we have employed this
      operation for 19 living donors (12 lateral segmentectomies and 7 left
      hepatectomies) and compared parameters between the 19 donors and 34 previous
      donors who underwent the procedure with standard incision (11 lateral
      segmentectomies and 23 left hepatectomies). RESULTS: The resultant length of
      incision was significantly reduced in operations with reduced incision length as
      compared with standard incision. Clinical outcomes such as operation time and
      length of hospital stay were comparable or significantly reduced with the reduced
      incision. The resultant incision length remained within 10 and 12 cm in lateral
      segmentectomy and left hepatectomy cases, respectively, whose body mass index was
      less than 22. CONCLUSION: It appears to be feasible to reduce the incision length
      for living donor left-side hepatectomy, especially in nonobese cases.

PMID- 24935305
TI  - A new formula as a predictive score of post-liver transplantation outcome:
      postoperative MELD-lactate.
AB  - INTRODUCTION: Liver transplantation (OLT) involves a 5% to 10% 30-day mortality
      rate. Multiple scores have been used as predictors of early postoperative
      mortality, such as the original Model for End-stage Liver Disease (MELD) and MELD
      sodium. Investigations have been conducted over the last 5 years to find new
      predictors of early post-OLT mortality. OBJECTIVE: The aim of this study was to
      develop a new mathematical model to predict the individual chance of 30-day
      mortality after OLT. METHODS: The study was conducted on 58 patients submitted to
      OLT at the University Hospital, between October 2008 and March 2012. The 29
      latest survivor and 29 latest nonsurvivor cases were selected. Arterial blood
      sodium, lactate, international normalized ratio, total bilirubin, and creatinine
      values were determined 1 hour after the end of surgery. The MELD original
      equation, MELD sodium, and new MELD lactate were also elaborated. The results
      were analyzed by the Mann-Whitney and Wilcoxon tests. The level of significance
      was set at .05. RESULTS: The new formula elaborated was as follows: MELD lactate
      = 5.68 * loge (lactate) + 0.64 * (Original MELD) + 2.68. The MELD lactate values
      were significantly higher than the MELD sodium and original MELD values (P <
      .05). The area under the receiver operating characteristic curve of MELD lactate
      in predicting the outcome of patients submitted to OLT was 0.80, as opposed to
      0.71 for the original MELD and 0.72 for MELD sodium (P < .05). CONCLUSION: The
      postoperative MELD lactate score proved to be more specific and sensitive than
      the original MELD and MELD sodium as a predictive model of the outcome of
      patients submitted to OLT.

PMID- 24935306
TI  - Presurgical transarterial chemoembolization does not increase biliary stricture
      incidence in orthotopic liver transplant patients.
AB  - INTRODUCTION: The goal of this study was to compare the incidence of biliary
      strictures in orthotopic liver transplant (OLT) patients treated with previous
      transarterial chemoembolization (TACE) versus those with no TACE history.
      PATIENTS AND METHODS: A single-center retrospective review was performed on 248
      patients who underwent OLT from 2006 to 2012. Patient demographic
      characteristics, history of TACE for treatment of hepatocellular carcinoma, OLT
      data, and biliary stricture data were obtained. TACE was generally performed in a
      segmental manner using chemotherapy to ethiodized oil mixture (1:1). Clinically
      significant biliary strictures resulting in cholestasis or obstructive jaundice
      were diagnosed by using endoscopic retrograde cholangiopancreatography. Group
      characteristics were compared by using the Wilcoxon rank sum test, chi(2)
      analysis, and Kaplan-Meier statistics with log-rank comparison. RESULTS: Forty
      six patients (35 men, 11 women; median age, 58 years) with a history of pre-OLT
      TACE were compared with 185 patients (111 men, 74 women; median age, 54 years)
      with no history of TACE. TACE and non-TACE patients had 30% and 31% cumulative
      incidence of biliary stricture, respectively. The median time to stricture was
      not reached in either group. There was no statistically significant difference in
      biliary stricture incidence (P = .928) or time to biliary stricture development
      (P = .803). Biliary strictures were primarily anastomotic in location in both
      groups: 79% in TACE patients and 84% in non-TACE patients (P = .233).
      CONCLUSIONS: Selective TACE treatment of hepatocellular carcinoma in
      pretransplant patients does not increase the rate of posttransplant biliary
      strictures. These findings corroborate the safety of TACE in the treatment of
      hepatocellular carcinoma in potential OLT patients as a bridge to
      transplantation.

PMID- 24935307
TI  - Serum fractalkine and interferon-gamma inducible protein-10 concentrations are
      early detection markers for acute renal allograft rejection.
AB  - OBJECTIVE: The aims of this study were to determine if characterization of serum
      concentrations of interferon-gamma inducible protein-10 (IP-10), fractalkine, and
      their receptors (CXCR3 and CX3CR1) were predictive of acute allograft rejection
      in kidney transplant recipients. METHODS: Kidney transplant recipients (n = 52)
      were enrolled in this study and divide into either the acute rejection (AR, n =
      15) or non-acute rejection (NAR, n = 35) groups. Serum samples from recipients
      were collected 1 day prior to transplantation and on days 1, 3, 5, 7, and 9 post
      transplantation. The accuracy of chemokine concentrations for predicting acute
      rejection episodes was evaluated using receiver operator characteristic (ROC)
      curves. RESULTS: AR was diagnosed in 15 patients based on histologic changes to
      renal biopsies. AR patients had significantly higher serum fractalkine, CXCR1, IP
      10, and CXCR3 levels compared to levels observed in the NAR group and healthy
      controls. Fractalkine and IP-10 had the largest area under the ROC curve at 0.86
      (95% confidence interval: 0.77-0.96). Following steroid therapy, chemokine levels
      decreased, which may serve to predict the therapeutic response to steroid
      therapy. CONCLUSION: Measuring serum levels of fractalkine, IP-10, and their
      receptors (especially the fractalkine/IP-10 combination) may serve as a
      noninvasive approach for the early diagnosis of renal allograft rejection.

PMID- 24935308
TI  - Incidental hepatocellular carcinoma: risk factors and long-term outcome after
      liver transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) currently represents the
      treatment of choice for early hepatocellular carcinoma (HCC). Preoperatively
      known HCC (pkHCC) is diagnosed via imaging methods before OLT or before HCC is
      found postoperatively in the liver explant, denoted as incidental HCC (iHCC). The
      aim of this study was a comprehensive analysis of the post-transplantation
      survival of patients with iHCC and the identification of risk factors of iHCC
      occurrence in cirrhotic liver. METHODS: We retrospectively reviewed 33 adult
      cirrhotic patients with incidentally found HCC, comparing them with 606 tumor
      free adult cirrhotic patients with end-stage liver disease (group Ci) who
      underwent OLT in our center from January 1995 to August 2012. Within the same
      period, a total of 84 patients underwent transplantation for pkHCC. We compared
      post-transplantation survivals of iHCC, Ci, and pkHCC patients. In the group of
      cirrhotic patients (Ci + iHCC), we searched for risk factors of iHCC occurrence.
      RESULTS: There was no difference in sex, Model for End-Stage Liver Disease score,
      and time spent on the waiting list in either group. In the multivariate analysis
      we identified age >57 years (odds ratio [OR], 3.37; 95% confidence interval [CI],
      1.75-8.14; P < .001), hepatitis C virus or alcoholic liver disease (OR, 3.89; 95%
      CI, 1.42-10.7; P < .001), and alpha-fetoprotein level >6.4 MUg/L (OR, 6.65; 95%
      CI, 2.82-15.7; P = .002) to be independent predictors of iHCC occurrence. Both
      the 1-, 3-, and 5-year overall survival (OS) and the 1-, 3- and 5-year recurrence
      free survival (RFS) differed in iHCC patients compared with the Ci group (iHCC:
      OS 79%, 72%, and 68%, respectively; RFS 79%, 72%, and 63%, respectively; vs Ci:
      OS = RFS: 93%, 94%, and 87%, respectively; P < .001). CONCLUSIONS: The survival
      of iHCC patients is worse than in tumor-free cirrhotic patients, but similar to
      pkHCC patients. The independent risk factors for iHCC occurrence in cirrhotic
      liver are age, hepatitis C virus, or alcoholic liver disease etiology of liver
      cirrhosis and alpha-fetoprotein level.

PMID- 24935309
TI  - The comparisons of hepatitis C virus RNA level between intraoperative blood
      salvage (cell saver) and systemic hepatitis C virus RNA kinetics during liver
      transplantation.
AB  - BACKGROUND: Cell Saver (CS; Haemonemic Corp, Braintree, Mass, United States) is
      frequently used to decrease transfusion requirements of homologous blood during
      liver transplantation (OLT). However, the use of CS in hepatitis C virus (HCV)
      infected recipients is still debated owing to the potential elevation of HCV RNA
      level. In this study, we compared HCV RNA levels of CS blood with a series of
      blood samples obtained from HCV-infected OLT recipients. METHODS: Twelve HCV
      infected patients with >50,000 copies/mL of HCV RNA were enrolled. HCV RNA was
      measured immediately after induction (I), at the end of anhepatic period (II), at
      the end of operation (III), and from the first returned blood in CS (CSb). HCV
      RNA level at each time period was compared. RESULTS: HCV RNA levels ranged from
      77,931 to 9,072,000 copies/mL at I. When compared to I, HCV RNA levels were
      reduced to 11.1% +/- 13.0% and 0.7% +/- 1.0% at II and III, respectively. Also,
      the RNA level reduced to 3.0% +/- 2.0% of I after CS processing. The HCV RNA
      level at I was significantly higher than the levels at II, III, and CSb (P =
      .012, each), and the level at II was significantly higher than the level at III
      (P = .012). The HCV RNA level at CSb showed no statistical difference with the
      levels at II, but it was significantly higher than the level at III (P = .042).
      CONCLUSIONS: The use of CS in HCV-infected OLT recipients seems to carry no
      additional risk with respect to intraoperative HCV RNA kinetics.

PMID- 24935310
TI  - Atrial fibrillation in patients undergoing liver transplantation-a single-center
      experience.
AB  - BACKGROUND: As the prevalence of atrial fibrillation rises with age and older
      patients increasingly receive transplants, the perioperative management of this
      common arrhythmia and its impact on outcomes in liver transplantation is of
      relevance. METHODS: Retrospective review of 757 recipients of liver
      transplantation from January 2002 through December 2011. RESULTS: Nineteen
      recipients (2.5%) had documented pre-transplantation atrial fibrillation. Sixteen
      patients underwent liver and 3 a combined liver-kidney transplantation. Three
      patients died within 30 days (84.2% 1-month survival) and another 3 within 1 year
      of transplantation (68.4% 1-year survival). Compared with patients without atrial
      fibrillation, the relative risk of death in the atrial fibrillation group was
      5.29 at 1 month (P = .0034; 95% confidence interval [CI], 1.73-16.18) and 3.28 at
      1 year (P = .0008; 95% CI, 1.63-6.59). Time to extubation and intensive care unit
      (ICU) and hospital readmissions were not different from the control cohort. Rapid
      ventricular response requiring treatment occurred in 4 patients during surgery
      and 7 after surgery, resulting in 3 ICU and 3 hospital readmissions. CONCLUSIONS:
      The results suggest that patients with atrial fibrillation may be at increased
      risk of mortality after liver transplantation. Optimization of medical therapy
      may decrease ICU and hospital readmission due to rapid ventricular response.

PMID- 24935311
TI  - Infection complications and pattern of bacterial resistance in living-donor liver
      transplantation: a multicenter epidemiologic study in Egypt.
AB  - INTRODUCTION: Data on the prevalence and pattern of infection after living-donor
      liver transplantation (LDLT) are scarce in Egypt. We therefore conducted this
      study to quantify the incidence, risk factors, and pattern of bacterial
      resistance post-LDLT in 3 hospitals in Egypt. PATIENTS AND METHODS: We conducted
      a retrospective, multicenter study of the medical records of 246 patients who
      underwent LDLT between January 2006 and April 2011 at 3 transplant centers in
      Egypt. RESULTS: Of 246 patients enrolled in this study, 127 (52%) developed
      infectious complications after LDLT, with 416 episodes of infection occurring
      within 3 months of transplantation. Biliary tract infection was the most common,
      occurring in 169 (40.6%) patients. The rate of infection with Gram-negative
      bacteria was higher than that of infection with Gram-positive bacteria (310 [74%]
      vs 87 [21%]; P < .001). Overall, 75% of Gram-negative isolates were multidrug
      resistant. Significant independent risk factors for infection were portal vein
      thrombosis (odds ratio, 2.4; P = .037) and biliary complications (odds ratio,
      5.4; P < .001). CONCLUSIONS: Our data showed a high-resistance pattern of
      bacterial infection after LDLT in Egypt. Early biliary complications were an
      independent risk factor for bacterial infection.

PMID- 24935313
TI  - Conversion from twice-daily to once-daily tacrolimus in simultaneous pancreas
      kidney transplant patients.
AB  - BACKGROUND: Data on the effectiveness of once-daily tacrolimus (Tac-QD) in
      simultaneous pancreas-kidney (SPK) transplant patients are limited, which is of
      particular concern because diabetic gastroparesis may affect absorption. The aim
      of this study was to evaluate the clinical impact of converting SPK patients from
      twice-daily (Tac-BD) to Tac-QD. METHODS: From November 2008 to August 2011, 27
      SPK recipients (out of 130) were converted from Tac-BD to Tac-QD. Demographics,
      prescribed doses, trough levels, and creatinine, glucose, and HbA1c values were
      collected prospectively at the time of conversion and at 1, 2, 3, 6, and 12
      months after conversion. RESULTS: The mean time from transplantation to
      conversion was 35.81 +/- 27.31 months, with 20 patients (74.07%) converted to Tac
      QD >12 months after transplantation. There were no significant differences in the
      tacrolimus dose and trough levels before and after conversion and at all points
      during the follow-up. Creatinine, glucos,e and HbA1c levels remained stable
      throughout. Eight patients (29.63%) with gastroparesis had clinical outcomes,
      drug doses, and trough levels similar to all other patients. CONCLUSIONS: Stable
      SPK recipients can safely be converted from Tac-BD to Tac-QD, with no clinical
      impact on the transplant function. Gastroparesis does not appear to influence
      tacrolimus dose requirements or trough levels.

PMID- 24935312
TI  - Analysis and forecast for multidrug-resistant Acinetobacter baumannii Infections
      among liver transplant recipients.
AB  - BACKGROUND: Acinetobacter baumannii (Ab) has become an important pathogenic
      bacterium with specific epidemic features in the intensive care unit. We explored
      the epidemiology of multidrug-resistant Ab infections among liver transplant
      recipients at the Liver Transplantation Center, 1st Affiliated Hospital of
      Shanghai Jiao Tong University. METHODS: Seventeen multidrug-resistant Ab strains
      were isolated from the sputum and bronchoalveolar lavage fluid specimens of 249
      liver transplant recipients from January 2007 to December 2009. The drug
      resistance and minimum inhibitory concentration (MIC) for the 17 Ab strains were
      determined. The Ab strains were genotyped with the use of repetitive element
      based polymerase chain reaction. The risk factors were also characterized by
      single-factor and multifactor analysis to the clinical data of the 249 liver
      transplant recipients. RESULTS: The drug sensitivity results showed that the 17
      Ab strains isolated displayed 100% drug resistance rate to aminoglycosides
      (gentamicin), quinolones (ciprofloxacin), penicillins (piperacillin),
      cephalosporins (ceftazidime, cefotaxime, and cefepime), and carbapenems (imipenem
      and meropenem). The 17 Ab strains could be divided into 3 genotypes: 1, 1, and 15
      strains for types A, C, and B, respectively. Fungal culture positivity after
      operation (odds ratio [OR], 5.470) and tracheal intubation twice (OR, 11.538)
      were the independent risk factors for multidrug-resistant Ab strain infection.
      CONCLUSIONS: Type B multidrug-resistant Ab strains are prevalent in the liver
      transplantation center, and they could be transmitted clonally. Liver transplant
      recipients with postoperational fungal culture positivity and tracheal intubation
      twice are prone to multidrug-resistant Ab infections. Therefore, a high degree of
      vigilance should be paid to those recipients to avoid nosocomial Ab infections.

PMID- 24935314
TI  - The impact of pretransplantation urgency status and the presence of a ventricular
      assist device on outcome after heart transplantation.
AB  - INTRODUCTION: There are conflicting reports on the posttransplantation morbidity
      and mortality of patients listed urgently and/or supported by a ventricular
      assist device (VAD). The aim of this study was to analyze the outcomes with
      regard to pretransplantation condition (elective, urgent, VAD). METHODS: All
      adult recipients between January 1, 2005, and October 31, 2012, were included.
      Demographics; preoperative, operative, and postoperative data; outpatient follow
      up; and donor characteristics were collected and analyzed. RESULTS: Of a total of
      74 patients, 19 were listed urgently, 20 had a Berlin Heart EXCOR BVAD
      (biventricular assist device) (Berlin Heart, Berlin, Germany) (8 urgent), 7 had a
      Berlin Heart INCOR left VAD (Berlin Heart, Berlin, Germany) (2 urgent), and 2 had
      a HeartWare left VAD (HeartWare International, Framingham, Mass, USA) (none
      urgent). Mean age was 52 +/- 12years. The overall 30-day, 1-year, and 3-year
      survival was 90% +/- 3%, 79% +/- 5%, and 66% +/- 7%. There was no difference in
      survival when comparing urgently listed (95% +/- 5%, 84% +/- 8%, 74% +/- 12%) and
      elective patients (89% +/- 4%, 77% +/- 6%, 63% +/- 8%; P = .4), and VAD patients
      (86% +/- 6%, 76% +/- 8%, 63% +/- 11%) and those without mechanical support (93%
      +/- 4%, 81% +/- 6%, 69% +/- 9%; P = .6). In-hospital outcomes and long-term
      complications were also comparable. CONCLUSIONS: Our series suggests that urgent
      patients and patients on a VAD have a posttransplantation outcome comparable to
      elective patients and patients without a VAD. These data support the
      effectiveness of the current practice of listing for heart transplantation.

PMID- 24935315
TI  - Outcomes in patients receiving HeartMate II versus HVAD left ventricular assist
      device as a bridge to transplantation.
AB  - OBJECTIVE: Ventricular assist devices have become a standard treatment for
      patients with advanced heart failure. We present data comparing results after
      implantation of HeartMate II (HM II) versus HVAD (HW) left ventricular assist
      devices (LVADs) for the past 7 years at our institution. METHODS: From July 2006
      to August 2012, 121 consecutive patients underwent LVAD implantation: 70 (57.9%)
      received HM II and 51 (42.1%) HW. Patient demographics, perioperative
      characteristics, and laboratory parameters as well as postoperative outcome were
      compared retrospectively. RESULTS: Patients in the HM II group were significantly
      younger (P < .01), with more deranged liver function (higher bilirubin [P = .02]
      and alanine aminotransferase [P = .01] levels), and had a significantly higher
      rate of preoperative infections requiring antibiotic treatment (P = .02) and a
      higher body core temperature (P < .01). Other demographic and preoperative
      parameters did not show statistical differences. Most postoperative
      characteristics were also similar between the two groups. HM II patients had a
      significantly higher transfusion rate, but there were no differences in incidence
      of resternotomy (P = .156). Recovery and VAD explantation were more likely in the
      HM II group (P = .02). Although there was no significant difference in survival
      (log rank test: P = .986; Breslow test: P = .827), HM II patients were more
      likely to develop a percutaneous site infection (P = .01). CONCLUSIONS: Both HM
      II and HW provide similar early postoperative outcome and good long-term
      survival. The differences observed between the groups may be related to
      demographic and preoperative factors rather than the type of the device used.

PMID- 24935316
TI  - Mechanical circulatory support in advanced heart failure: single-center
      experience.
AB  - BACKGROUND: Currently, ventricular assist device (VAD) or total artificial heart
      (TAH) mechanical support provides an effective treatment of unstable patients
      with advanced heart failure. We report our single-center experience with
      mechanical circulatory support therapy. METHODS: From March 2002 to December
      2012, 107 adult patients (mean age, 56.8 +/- 9.9 y; range, 31-76 y) were primarly
      supported on temporary or long-term VAD or TAH support as treatment for
      refractory heart failure at our institution. Temporary extracorporeal radial VAD
      support (group A) was established in 49 patients (45.7%), and long-term
      paracorporeal and intracorporeal VAD or TAH (group B) in 58 patients (54.2%).
      Left ventricular (LVAD) support was established in 55 patients (51.4%; n = 33,
      Heartmate II; n = 6, Heartmate I XVE; n = 4, Heartware HVAD; and n = 12,
      Centrimag) and biventricular (BVAD/TAH) support (group B) in 28 patients (26.1%;
      n = 10, Thoratec paracorporeal; n = 2, Heartware HVAD, n = 1, Thoratec
      implantable; n = 1, Syncardia TAH; and n = 14, Centrimag). The temporary
      Centrimag was the only device adopted as isolated right ventricular (RVAD)
      support, and it was inserted in 24 patients (22.4%). RESULTS: In group A, overall
      mean support time was 10.2 +/- 6.6 days (range, 3-43 d). In group B, LVAD mean
      support time was 357 +/- 352.3 days (range, 1-902 d) and BVAD/TAH support time
      was 98 +/- 82.6 days (range, 8-832 d). In group A, the overall success rate was
      55.1% (27 patients). In group B, LVAD overall success rate was 74.4% (32
      patients) and BVAD/TAH success rate was 50% (7 patients). Overall heart
      transplantation rate for both groups was 27.1% (n = 2, group A; n = 27, group B).
      Overall 1-year and 5-year survivals after heart transplantation were 72.4% (n =
      21) and 58.6% (n = 17), respectively. CONCLUSIONS: Mechanical circulatory support
      is an effective strategy even in cases of end-stage heart failure according to
      our experience. Further improvement of VAD and TAH technologies may support their
      adoption as an encouraging alternative to heart transplantation in the near
      future.

PMID- 24935317
TI  - Cancer-free survival following alemtuzumab induction in heart transplantation.
AB  - BACKGROUND: The malignancy rate after alemtuzumab (C-1H) induction in cardiac
      transplantation is unknown. METHODS: A retrospective analysis from a single
      center for all patients that underwent cardiac transplantation from January 2000
      to January 2011 and that had no history of malignancy before transplantation was
      performed. Patients induced with alemtuzumab were compared with a group of
      patients receiving thymoglobulin or no induction and assessed for 4-year cancer
      free post-heart transplantation survival. RESULTS: Of 402 patients included, 185
      (46.0%) received alemtuzumab, 56 (13.9%) thymoglobulin, and 161 (40.0%) no
      induction. Baseline characteristics did not differ between groups: mean age 54.0
      years, male 77.1%, white 88.6%, ischemic cardiomyopathy 49.0%. The calcineurin
      inhibitor was tacrolimus in 98.9% of alemtuzumab patients, 98.2% of thymoglobulin
      patients, and 87.0% of the noninduced (P < .001). The secondary agent was
      mycophenolate mofetil in all but 16 noninduced patients (9.9%), who received
      azathioprine. The 4-year cancer-free survival did not differ between groups:
      88.1% alemtuzumab, 87.5% thymoglobulin, 88.2% noninduction; P = .088. The 4-year
      nonskin cancer-free survival was 96.8% for the alemtuzumab group, 96.4% for the
      thymoglobulin group, and 95.7% for the noninduced; P = .899. CONCLUSIONS: Neither
      the 4-year cancer-free survival nor the 4-year nonskin cancer-free survival
      differed between the alemtuzumab, thymoglobulin, and noninduced groups.

PMID- 24935318
TI  - Immunohistochemical quantification of inflammatory cells in endomyocardial biopsy
      fragments after heart transplantation: a new potential method to improve the
      diagnosis of rejection after heart transplantation.
AB  - Inconsistencies in cardiac rejection grading systems corroborate the concept that
      the evaluation of inflammatory intensity and myocyte damage seems to be
      subjective. We studied in 36 patients the potential role of the
      immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy
      (EMB) as an objective tool, testing the hypothesis of correlation between the
      International Society for Heart and Lung Transplantation 2004 rejection and IHC
      counting of inflammatory cells. We observed a progressive increment in CD68+
      cells/mm(2) (P = .000) and CD3+ cells/mm(2) (P = .000) with higher rejection
      grade. A strong correlation between the grade of cellular rejection and both
      CD68+ cells/mm(2) and CD3+ cells/mm(2) was obtained (P = .000). One patient with
      CD3+ and CD68+ cells/mm(2) above the upper limit of the 95% confidence interval
      for cells/mm(2) found in rejection grade 1R evolved to rejection grade 2R without
      treatment. In patients with 2R that did not respond to treatment the values of
      CD68+ or CD3+ cells were higher than the overall median values for rejection
      grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+
      cells/mm(2) areas under the receiver operating characteristic curves were 0.956
      and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in
      EMB seems to have additive potential role in evaluation of EMB for the diagnosis
      and prognosis of rejection episodes.

PMID- 24935319
TI  - Selecting oversized donor cardiac allografts for patients with pulmonary
      hypertension may be unnecessary.
AB  - INTRODUCTION: There is a tendency to favor oversized donor hearts for heart
      transplant candidates affected by mild to moderate pulmonary hypertension (PHTN).
      We hypothesize that both undersized and oversized donor hearts fare equally well
      in this setting. METHODS: A total of 107 cases from 2003 to 2008 were
      retrospectively reviewed and subsequently divided into those receiving organs
      from undersized donors (group 1: donor weight/recipient weight <= 0.90, n = 37)
      and oversized donors (group 2: donor weight/recipient weight >= 1.2, n = 70).
      PHTN was identified in the perioperative period in those patients with systolic
      pulmonary artery pressure (SPAP) >= 40 mm Hg. Endpoints of mortality and
      hemodynamic data were investigated. RESULTS: Of 107 patients, 37 received
      undersized donor allografts, with a mean donor-to-recipient weight ratio of 0.8,
      and 70 received oversized donors allografts, with a mean donor-to-recipient ratio
      of 1.4. Perioperative PAH was diagnosed in 20 of the 37 (54%) patients from the
      undersized group (mean SPAP = 45.9 mm Hg) and 41 of 70 (59%) patients from the
      oversized group (mean SPAP = 46.5 mm Hg). There was no significant difference in
      right ventricular function at 1 week, 1 month, or 6 months. Left ventricular
      function was similar between both groups at 6 months (P = .22). The mean SPAP in
      the undersized group was 45.9, 33.4, 31.8, and 23.1 mm Hg at the perioperative, 1
      week, 1 month, and 6 month time points, respectively. Corresponding mean SPAP for
      the oversized group was 46.5, 35.0, 29.4, and 26.1 mm Hg. The 1 month, 1 year,
      and 3 year survivals were similar in both groups. CONCLUSIONS: Oversized and
      undersized donor hearts fared equally well in the setting of mild to moderate
      perioperative PAH. This in addition to the propensity for resolution of pulmonary
      hypertension over time suggests that the current practice of favoring oversized
      donor hearts for patients with pre-transplantation PAH may be unwarranted.

PMID- 24935320
TI  - Long-term outcomes of orthotopic heart transplantation for hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease
      characterized by asymmetric or symmetric ventricular hypertrophy in the absence
      of an obvious clinical cause. Orthotopic heart transplantation (OHT) has been
      performed in patients who have refractory symptoms despite medical therapy and
      surgical septal myectomy. However, there is a paucity of data on outcomes of HCM
      patients who undergo OHT. METHODS: Data on 462 consecutive patients who underwent
      OHT at UCLA Medical Center from 1996 to 2004 were retrospectively collected. The
      clinical data on the 11 patients with HCM were identified. RESULTS: The majority
      of the HCM patients were male (64%). The mean age of the patient was 45 +/- 8
      years, and the mean donor age was 35 +/- 18 years. The mean ischemia time was 226
      +/- 60 minutes. There was 1 in-hospital death secondary to septic shock. At a
      median duration of follow-up of 4.5 years (mean, 4.4 +/- 3.2 years), there were 3
      additional deaths. Compared with the 451 OHT patients who did not have HCM, there
      was no difference in survival (P = .13), development of cardiac allograft
      vasculopathy (P = .46), or rejection (P = .71). There was no evidence of HCM
      recurrence in biopsies from the donor heart. CONCLUSIONS: OHT is a viable
      treatment option for patients with end-stage HCM refractory to standard
      therapies.

PMID- 24935321
TI  - Body mass index in lung transplant candidates: a contra-indication to transplant
      or not?
AB  - BACKGROUND: According to International Society of Heart and Lung Transplantation
      criteria, high body mass index (BMI; >= 30 kg/m(2)) is a relative
      contraindication for lung transplantation (LT). On the other hand, low BMI may be
      associated with worse outcome. We investigated the influence of pre-LT BMI on
      survival after LT in a single-center study. METHODS: Patients were divided
      according to the World Health Organization criteria into 4 groups: BMI <18.5
      kg/m(2) (underweight), BMI 18.5-24.9 kg/m(2) (normal weight), BMI 25-29.9 kg/m(2)
      (overweight), and BMI >= 30 kg/m(2) (obesity). An additional analysis was made
      per underlying disease. RESULTS: BMI was determined in a cohort of 546 LT
      recipients, of which 28% had BMI <18.5 kg/m(2). Underweight resulted in similar
      survival (P = .28) compared with the normal weight group. Significantly higher
      mortality was found in overweight (P = .016) and obese patients (P = .031)
      compared with the normal-weight group. Subanalysis of either underweight (P =
      .19) or obese COPD patients (P = .50) did not reveal worse survival. In patients
      with interstitial lung disease, obesity was associated with increased mortality
      (P = .031) compared with the normal-weight group. In cystic fibrosis patients,
      underweight was not associated with a higher mortality rate (P = .12) compared
      with the normal-weight group. CONCLUSIONS: Low pre-LT BMI did not influence
      survival rate in our cohort, independently from underlying disease.

PMID- 24935322
TI  - HRCT features of acute rejection in patients with bilateral lung transplantation:
      the usefulness of lesion distribution.
AB  - PURPOSE: This study sought to evaluate the high-resolution computed tomography
      (HRCT) features of acute rejection and to assess the diagnostic accuracy of HRCT
      for acute rejection considering distribution of lesions in patients with
      bilateral lung transplantation (BLT). MATERIALS AND METHODS: Between March 2010
      and June 2012, 48 transbronchial lung biopsies (TBLBs) and HRCT were performed
      simultaneously in 26 patients who underwent BLT. We evaluated the presence of
      ground glass opacity (GGO), consolidation, nodule, bronchial wall thickening,
      interlobular septal thickening, pleural effusion, atelectasis, bronchiectasis,
      and cardiomegaly on the HRCT images. The distribution of lesions was analyzed
      according to bilaterality or upper/lower predominance. Acute rejection was
      determined on the basis of the pathologic results of TBLB. We evaluated potential
      correlations of HRCT features with acute rejection, then assessed overall
      diagnostic accuracy of various HRCT features in combination to diagnose acute
      rejection in the transplanted lung. RESULTS: Among the 48 TBLBs, 8 were diagnosed
      as acute rejection (A1, 4 cases; A2, 2 cases; and A3, 2 cases) pathologically.
      Two A1 rejections and one A2 rejection appeared normal on computed tomography
      images. Without considering the distribution of lesions, interlobular septal
      thickening was significantly associated with acute rejection (P = .010) only.
      Regarding the distribution of lesions on HRCT images, not only interlobular
      septal thickening but also GGO was significantly associated with acute rejection
      (P < .05). The sensitivity, specificity, positive predictive value, negative
      predictive value, and overall accuracy of the HRCT scan in the evaluation of
      acute rejection were 50%, 97.5%, 80%, 90.1%, and 89.6%, when the bilateral GGO
      and interlobular septal thickening with lower predominance were considered as the
      positive finding. CONCLUSIONS: HRCT findings considering lesion distribution
      could be a useful tool in diagnosing acute rejection in patients with BLT.

PMID- 24935323
TI  - Impact of donor-to-recipient weight ratio on survival after bilateral lung
      transplantation.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      donor-to-recipient weight ratio and post-transplantation survival. METHODS: From
      February 1988 to November 2006, 255 adult bilateral lung transplantation patients
      from 2 different centers were retrospectively analyzed. The cohort was divided
      into 4 groups depending on the quartile ranges of the donor-to-recipient weight
      ratio. A time-to-event analysis was performed for risk of death after
      transplantation conditional on 5-year survival using Kaplan-Meier and Cox
      proportional hazards models. RESULTS: The mean weight ratio for the study cohort
      was 1.23 +/- 0.39. For all lung transplant recipients during the study period,
      survival rate at 5 years was 58%. Median survival was 6.3 years in the cohort
      subgroup with weight ratio <1.23, whereas the median survival was 7.7 years for
      the cohort subgroup with weight ratio >1.23. Weight ratio >1.23 recipients had a
      significant survival advantage out to 5 years compared with weight ratio <1.23
      recipients (66.1% vs 51.1%, P = .0126). With the aim to assess underweight and
      overweight donors vs recipients, we have divided all patients into 4 groups, from
      quartile 1 to 4, based on donor-to-recipient weight ratio. Weight ratio strata
      affected overall survival, with quartile 1 (lower weight ratio recipients)
      experiencing the lowest 5-year survival (39.1%), followed by quartile 2 (57.8%),
      quartile 4 (68.2%), and quartile 3 (70.3%) recipients. The effect of weight ratio
      strata on survival was statistically significant for the quartile 1 recipients
      (lower quartile) as compared with the 3 other quartiles. CONCLUSIONS: Our
      findings show a statistically significant effect of donor-to-recipient weight
      ratios on bilateral lung transplantation survival. A higher donor-to-recipient
      weight ratio was associated with improved survival after bilateral lung
      transplantation and likely reflects a mismatch between a relatively overweight
      donor vs recipient. In contrast, a lower donor-to-recipient ratio was associated
      with increased mortality after bilateral lung transplantation.

PMID- 24935325
TI  - Modified busulfan and cyclophosphamide conditioning regimen for allogeneic
      hematopoietic stem cell transplantation in the treatment of patients with
      hematologic malignancies.
AB  - OBJECTIVE: We aim to evaluate the clinical efficacy of a modified busulfan and
      cyclophosphamide (BU/CY) conditioning regimen for allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) in the treatment of hematologic malignancies.
      METHODS: A total of 45 patients with hematologic malignancies were treated using
      stem cell transplantation between March 2007 and June 2012. All the patients
      received a modified BU/CY conditioning regimen before transplantation. The
      outcomes of the patients were followed up including mortality, survival, relapse,
      and complications. RESULTS: The median of follow-up duration was 527 days. All
      the patients who received modified BU/CY conditioning regimen achieved
      hematopoietic recovery successfully. Among the patients, 24 were survived without
      complications, 5 had relapsed hematologic malignancies, and 16 died. The median
      time to leucocyte engraftment was 14 days and to platelet engraftment was 12
      days. Acute graft-versus-host disease (aGVHD; grades I-IV) occurred in 15
      patients (30%). The cumulative incidence of grades I aGVHD was 22.2% (10
      patients), grades II was 6.7% (3 patients), and grades III-IV was 4.4% (2
      patients). Among 40 appreciable patients, 8 (20%) developed chronic GVHD. The
      incidence rate of hemorrhagic cystitis and veno-occlusive disease were 15.5% and
      2.2%, respectively. CONCLUSIONS: The modified BU/CY conditioning regimen for allo
      HSCT is effective and safe for the treatment of hematologic malignancies.

PMID- 24935324
TI  - The correlation between platelet activation and liver injury by conditioning and
      bone marrow transplantation.
AB  - Hepatic veno-occlusive disease (HVOD) is a common severe complication after
      transplantation which is closely related to liver sinusoidal endothelial cell
      (LSEC) injury. Although platelet activation might play a key role in the progress
      of HVOD, the relationship between the P-selectin and HVOD is still unclear. In
      this study, the P-selectin, liver functions, and observed damage of LSEC after
      transplantation were detected. The P-selectin, alanine aminotransferase (ALT) and
      bilirubin were first detected in the patients. The ALT of patients reached the
      first peak of 144 +/- 45.04 U/L, on day 7 after busulfan + cyclophosphamide
      (BU/CY) pretreatment, and reached the second peak of 220.5 +/- 40.58 U/L on day 7
      after transplantation. Similarly, the concentration of bilirubin increased BU/CY
      pretreatment and reached peak on day 15 after transplantation at 38.8 +/- 5.99
      MUmol/L. However, the level of P-selectin was significantly higher than normal
      levels for a long time and peaked on day 3 after BU/CY pretreatment and on day 12
      after transplantation (P < .05). Then the P-selectin, liver function, liver
      index, hepatocytes, and LSEC were observed using a transplantation model of
      C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient. The P-selectin, liver index,
      and liver function of total body irradiation (TBI) mice and bone marrow
      transplantation (BMT) mice were significantly increased, but the increase of TBI
      mice were more significant. On day 5, the ratio of TBI mice peripheral blood
      platelets which expressed P-selectin was higher and reached an earlier peak at
      15.6 +/- 2.63%, whereas that of BMT mice was 6.59 +/- 1.17%, and peaked on day 15
      at 8.36 +/- 1.55% (P < .05). Moreover, the ALT and bilirubin levels of TBI mice
      were higher and reached earlier peaks on day 5 at 58.65 +/- 1.43 U/L and 27.14 +/
      1.32 MUmol/L, respectively, whereas those of BMT mice peaked on day 5 at 50.22
      +/- 2.02 U/L and day 30 at 39.57 +/- 1.55 MUmol/L, respectively (P < .05). The
      LSEC damage and hepatocyte edema in BMT mice were most serious at day 15, and at
      day 30 injuries did not allow recovery. The liver score of TBI mice peaked on day
      5, whereas that of BMT mice peaked on day 15. Moreover, the degree of damage and
      platelet activation positively correlated. This study implied that P-selectin
      could be used as a predictor of HVOD.

PMID- 24935326
TI  - Intestinal ischemia after allogeneic stem cell transplantation: a report of four
      cases.
AB  - Gastrointestinal ischemia after allogeneic bone marrow transplantation is a rare
      complication not well-described in the literature. Herein we retrospectively
      review charts of four patients who developed intestinal ischemia after allogeneic
      bone marrow transplantation at our institution. The patients were found to be
      predominately younger males who presented with nonspecific abdominal pain. Graft
      versus-host disease was a common finding among all patients. Laboratory values
      suggestive of microangiopathy were present in two patients. Obesity and
      hypertriglyceridemia were cardiovascular risk factors found in these patients.
      The development of thrombotic microangiopathy and cardiovascular risk factors
      after allogeneic bone marrow transplantation may predispose patients to
      gastrointestinal ischemia and may portend a poor prognosis. 

PMID- 24935327
TI  - Haplotype analysis on chromosome 6p of tumor necrosis factor alpha, vascular
      endothelial growth factor A, and interleukin-17F alleles associated with corneal
      transplant rejection.
AB  - OBJECTIVE: The aim of this work was to investigate single-nucleotide
      polymorphisms (SNPs) in multiple genes on chromosome 6p in corneal transplant
      recipients known to be at increased risk of failure through immunologic rejection
      (ie, "high-risk" corneal transplants). Tumor necrosis factor alpha (TNF-alpha) is
      a key immunoregulatory cytokine in the ocular environment, interacting with a
      variety of factors in a synergistic way and playing a crucial role in many stages
      of the inflammatory response. Vascular endothelial growth factor (VEGF) is one of
      the most important angiogenic factors, supporting both hemangiogenesis and
      lymphangiogenesis, both key in transplant tolerance and rejection. Interleukin-17
      (IL-17) is a multifunctional cytokine produced by T-helper 17 cells, exerting
      specific effector functions during an immune response. Association of SNPs in all
      3 genes with corneal transplant outcome was therefore investigated. METHODS:
      Three hundred five corneal transplant recipients were followed for 3 years, and
      episodes of allograft rejection were recorded. With the use of patient DNA, 6
      SNPs of 3 different genes on chromosome 6p were investigated. The TNF-alpha
      promoter SNP -308 G/A (rs1800629) was analyzed with the use of induced
      heteroduplex generation; 2 VEGF-A functional variants were analyzed, -2578
      (rs699947) C/A and -1154 (rs1570360) G/A, with the use of Taqman genotyping
      assays; and 3 nonsynonymous IL-17F SNPs in exon 3 (negative strand), (rs2397084)
      A/G, (rs11465553) G/A, and (rs763780) A/G, were investigated with the use of
      direct sequencing. Haplotypes were inferred with the use of PHASE using positive
      strand alleles, and exact measures of association were determined with the use of
      Mid-P exact chi-square. RESULTS: Six common haplotypes were inferred, with the
      haplotype TNF-alpha (rs1800629), VEGF-A (rs699947), (rs1570360), IL-17F
      (rs763780), (rs11465553), and (rs2397084) ACGTCT having a significant association
      with corneal transplant rejection (odds ratio, 1.78; 95% confidence interval,
      1.01-3.11; P = .04). CONCLUSIONS: The results suggest that patients carrying a
      combination of SNPs for TNF-alpha, VEGF-A, and IL-17F of ACGTCT haplotype may
      have an increased risk of corneal allograft rejection compared with patients
      carrying other haplotypes.

PMID- 24935328
TI  - Functional tumor necrosis factor alpha polymorphisms and haplotype analysis in
      high-risk corneal transplantation.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) plays a critical role in
      diverse cellular processes including ocular immune tolerance, inflammation, and
      allograft rejection. The ubiquitous transcription factor nuclear factor kappa B
      (NF-kappaB) regulates expression of numerous genes. Induction of the TNF-alpha
      pathway is involved in the inflammatory response and loss of transplant
      tolerance. OBJECTIVES: We investigated functional single nucleotide polymorphisms
      (SNPs) in the promoter region of TNF-alpha and an insertion/deletion (indel)
      polymorphism of NF-kappaB1 in corneal transplant recipients considered to be at
      increased risk of immunological rejection (ie, high-risk corneal
      transplantations) and looked for any associations with corneal transplantation
      outcome. PATIENTS AND METHODS: Three hundred eighty-four full thickness corneal
      transplant recipients were followed for 3 years and episodes of reversible and
      irreversible allograft rejection were recorded. Using DNA obtained from these
      patients, 5 SNPs located in the promoter region -1031 T/C rs1799964, -863 C/A
      (rs1800630), -857 C/T (rs1799724), -308 G/A (rs1800629), and -238 G/A (rs361525),
      and one SNP upstream from the transcription start site (+489) rs1800610 of TNF
      alpha were analyzed using induced heteroduplex generation. A functional NF
      kappaB1 indel (-94) was also investigated. Haplotypes were inferred by PHASE and
      associations with rejection were determined by chi-square analysis. RESULTS: The
      TNF-alpha haplotype TCTGGA was significantly associated with reduced risk of
      corneal graft rejection (Pc < .005) and TCTAGA was associated with increased risk
      of rejection (Pc < .005) in high-risk corneal transplants. There was no
      association with the NF-kappaB1 indel (Pc > .05). CONCLUSION: According to
      haplotype frequencies, our results suggest that the TCTGGA haplotype may confer
      additional protection against risk of immunological rejection whereas TCTAGA may
      increase risk of corneal allograft rejection in the high-risk setting. However,
      both haplotypes were relatively rare and thus would not warrant genotyping for
      individual patient selection for anti-TNF therapy.

PMID- 24935329
TI  - Preconditioning donor livers with cromolyn or compound 48/80 prolongs recipient
      survival in a rat orthotopic liver transplantation model.
AB  - BACKGROUND: Acute rejection (AR) remains a challenge in organ transplantation.
      Preconditioning donor organs can reduce AR and prolong survival. Whether
      preconditioning with cromolyn (CRM), a mast cell (MC) stabilizer, or compound
      48/80 (CMP 48/80), a MC degranulator, can alleviate AR and prolong survival has
      not been studied. METHODS: We used the male-DA-to-female-Lewis-rat orthotopic
      liver transplantation (OLT) model. Donors were preconditioned with CRM in a MC
      stabilizing way (CRM group) or CMP 48/80 in a MC depleting way (CMP 48/80 group).
      Rats preconditioned with phosphate-buffered saline were used as controls (PBS
      group). After preconditioning, OLT surgeries were carried out. OLT male-Lewis-to
      female-Lewis-rats were used as the syngeneic group (syngeneic group). RESULTS:
      Rats in the PBS group developed AR rapidly and died at 7.40 +/- 1.14 days. Rats
      in the CRM and CMP 48/80 groups had significantly slower rejections and died at
      day 17.40 +/- 1.67 or 14.20 +/- 2.28, respectively (P < .05). Rats in the
      syngeneic group survived more than 60 days. Rejection activity indexes (RAIs) and
      liver functions were all alleviated through CRM or CMP 48/80 preconditioning.
      Interferon-gamma messenger RNA (mRNA) expressions were reduced and interleukin-10
      mRNA levels were higher in allografts in the CRM and CMP 48/80 groups, compared
      with the PBS group. These were confirmed by testing serum interferon-gamma and
      interlerkin-10. CONCLUSION: Preconditioning donor livers with CRM or CMP 48/80
      can reduce AR and prolong survival of recipients after OLT.

PMID- 24935331
TI  - Impact of ex vivo administration of mesenchymal stem cells on the function of
      kidney grafts from cardiac death donors in rat.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have been applied to the treatment of
      various diseases, and MSC administration in marginal donor grafts may help avoid
      the ischemia-reperfusion injury associated with solid organ transplants. Given
      the reports of side effects after intravenous MSC administration, local MSC
      administration to the target organ might be a better approach. We administered
      adipose tissue-derived MSCs (AT-MSCs) ex vivo to donor rat kidneys obtained after
      cardiac death (CD). METHODS: Using male Lewis rats (8-10 weeks), and a marginal
      transplant model of 1hr CD plus 1hr sub-normothermic ET-Kyoto solution
      preservation were conducted. AT-MSCs obtained from double-reporter (luciferase
      LacZ) transgenic Lewis rats were injected either systemically (1.0 * 10(6)
      cells/0.5 mL) to bilaterally nephrectomized recipient rats that had received a
      marginal kidney graft (n = 6), or locally via the renal artery (500 MUL ET-Kyoto
      solution containing the same number of AT-MSCs) to marginal kidney grafts, which
      were then preserved (1 hour; 22 degrees C) before being transplanted into
      bilaterally nephrectomized recipient rats (n = 8). Serum was collected to assess
      the therapeutic effects of AT-MSC administration, and the recipients of rats
      surviving to Day 14 were separately evaluated histopathologically. Follow-up was
      by in vivo imaging and histological LacZ staining, and tumor formation was
      evaluated in MSC-injected rats at 3 months. RESULTS: Systemic injection of MSC
      did not improve recipient survival. In vivo imaging showed MSCs trapped in the
      lung that later became undetectable. Ex vivo injection of MSCs did show a benefit
      without adverse effects. At Day 14 after RTx, 75% of the rats in the AT-MSC
      injected group (MSC[+]) had survived, whereas 50% of the rats in the AT-MSC-non
      injected group (MSC[-]) had died. Renal function in the MSC(+) group was improved
      compared with that in the MSC(-) group at Day 4. LacZ staining revealed AT-MSCs
      attached to the renal tubules at 24 hours after RTx that later became
      undetectable. Histopathologic examination showed little difference in fibrosis
      between the groups at Day 14. No teratomas or other abnormalities were seen at 3
      months.

PMID- 24935330
TI  - The protective effect of huperzine A against hepatic ischemia reperfusion injury
      in mice.
AB  - BACKGROUND: Nowadays, hepatic ischemia reperfusion (HI/R) injury is regarded as a
      serious concern in clinical practices. Huperzine A (HupA) is an alkaloid isolated
      from the Chinese folk medicine huperzia serrate, which has possessed diverse
      pharmacological actions. METHODS: A mouse model of HI/R was caused by clamping
      the hepatic artery, the hepatoportal vein, and the bile duct with a vascular
      clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The
      sham group experienced the identical procedure without hepatic ischemia. The HupA
      group received an injection into the tail vein 5 minutes prior to HI/R at the
      doses of 167 and 500 MUg/kg. The vehicle group was injected with physiological
      saline instead of HupA. The liver function was assessed by determinations of
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.
      Tissue levels of superoxide dismutase (SOD), catalase (CAT), malondiadehyde
      (MDA), and glutathione (GSH) were also measured spectrophotometrically. In
      addition, the activities of hepatic inflammatory mediators such as nuclear factor
      kappa B (NF-kappaB) p65, tumor necrosis factors-alpha (TNF-alpha, interleukin
      1beta (IL-1beta) and IL-6 were also measured. Furthermore, the apoptotic damage
      was evaluated by measuring caspase-3 activity in hepatic tissues. RESULTS:
      Treatment with HupA in mice at the doses of 167 and 500 MUg/kg remarkably reduced
      serum ALT and AST activities in HupA-treated ischemic mice. Furthermore, HupA
      treatment could enhance the activities of hepatic tissue SOD, CAT, and GSH but
      decrease MDA tissue content. The activities of inflammatory cytokines including
      NF-kappaB p65, TNF-alpha, IL-1beta and IL-6 were all decreased in ischemic mice
      treated with HupA. Colorimetric test results illustrated that a marked reduction
      of caspase-3 activity was found in the HupA-treated group compared with the
      vehicle group. CONCLUSION: Our present data suggest that HupA has a protective
      role against HI/R injury of mice and antioxidative, anti-inflammatory, and
      antiapoptotic actions are involved in its protection.

PMID- 24935332
TI  - Relationship between inflammation and sex hormone profile in female patients
      receiving different types of renal replacement therapy.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) experience female sexual
      dysfunction (FSD). The purpose of this study was to compare FSD in different
      types of renal replacement therapy and control patients. METHODS: The study was
      consisted of 47 renal transplantation (RT), 46 hemodialysis (HD), and 28
      continuous ambulatory peritoneal dialysis (CAPD) patients and 36 healthy control
      subjects. All groups were evaluated with the following scales: Female Sexual
      Function Index (FSFI) questionnaire, Short Form (SF)-36 questionnaires, and Beck
      Depression Inventory (BDI). Demographic data, laboratory values, and hormone
      levels were obtained. The patients with FSFI score <26.55 were accepted as
      experiencing sexual dysfunction. RESULTS: Overall, total FSFI scores in RT, HD,
      CAPD, and control were 22 (range, 2-35), 22.4 (4-34), 18.35 (2-34), and 29.6 (2
      35), respectively. The mean total FSFI score was not different in patients
      receiving different kinds of renal replacement therapy (P > .05) although they
      were significantly worse then the control group (P < .001). On regression
      analysis, age was significantly associated with FSD (beta = -0.14; P = .001). In
      addition, the physiologic health domain of SF-36 was significantly better in
      control groups (P < .001). The difference in terms of mean of BDI score did not
      reach statistical significance among patient groups (P > .05). Female sexual
      dysfunction score was negatively correlated with BDI (r = -0.371; P < .001) and
      positively correlated with the mental-physical components score of SF-36 (r =
      0.423 [P < .001] and r = 0.494 [P < .001], respectively) in all patients groups.
      Regarding the hormones of the patients, there was a significant difference
      between RT and the HD and CAPD groups in dihydroepiandrosterone sulfate (DHEAS; P
      < .001), RT and HD in prolactin (P < .001), and RT and CAPD in free testesterone
      (P < .001). CONCLUSIONS: Renal transplantation, hemodialysis, and peritoneal
      dialysis patients were at more risk of developing sexual dysfunction and lower
      quality of life scores than healthy subjects. Notably, the mode of renal
      replacement therapy had no impact on female sexual function.

PMID- 24935333
TI  - Hepatic stellate cells induce immunotolerance of islet allografts.
AB  - Activated hepatic stellate cells (HSCs) possess strong immune inhibitory
      activity. The present study highlighted the protective role of HSCs in islet
      transplantation. Recipients were randomly divided into 4 groups: a diabetic
      group, an HSC-alone group, an islet-alone transplant group, and a cotransplant
      group. Graft survival was compared among the 4 groups. Serum transforming growth
      factor beta (TGFbeta), tumor necrosis factor alpha, interleukin-1beta, and
      interferon gamma expression levels were measured. The infiltration of lymphocytes
      was observed via hematoxylin and eosin staining, and immunohistochemical
      examinations were performed. Results showed that allogeneic HSCs protect islet
      allografts better than syngeneic HSCs. There was significant prolonged graft
      survival and a higher level of TGFbeta in the cotransplant group (P < .01). The
      infiltration of lymphocytes in the cotransplant group was notably less than in
      the islet-alone group (P < .01). The formation of desmin-positive HSC packages
      was detected in the cotransplant group. In conclusion, allogeneic HSCs can better
      prolong the survival of islet allografts by stimulating TGFbeta expression and
      forming a biological capsule around the graft.

PMID- 24935334
TI  - Effects of antegrade and retrograde machine perfusion preservation on cardiac
      function after transplantation in canines.
AB  - INTRODUCTION: Most studies investigating machine perfusion preservation for heart
      transplantation perfuse through the aortic root (antegrade), but the coronary
      sinus (retrograde) is a potential option. We hypothesized that retrograde machine
      perfusion provides better functional protection than static storage, while
      avoiding the potential irregular perfusion seen when aortic insufficiency occurs
      with antegrade perfusion. MATERIALS AND METHODS: Eighteen canine donor hearts
      were arrested, procured, and stored in modified Celsior solution for 4 hours by
      using either static storage at 0 degrees C to 4 degrees C (n = 6) or machine
      perfusion preservation at 5 degrees C via the aortic root (antegrade, n = 6) or
      coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption
      were measured in perfused hearts. Hearts were reimplanted and reperfused for 6
      hours with hourly function calculated by using the preload recruitable stroke
      work (PRSW) relation. Myocardial water content was determined at the end of the
      experiment. RESULTS: Storage lactate levels and myocardial oxygen consumption
      were comparable in both perfused groups. The PRSW was increased immediately after
      bypass in the antegrade group (120.6 +/- 19.1 mm Hg) compared with the retrograde
      (75.0 +/- 11.3 mm Hg) and static (78.1 +/- 10.5 mm Hg) storage groups (P < .05).
      At the end of reperfusion, PRSW was higher in the retrograde group (69.8 +/- 7.4
      mm Hg) compared with the antegrade (40.1 +/- 6.8 mm Hg) and static (39.9 +/- 10.9
      mm Hg) storage groups (P < .05). Myocardial water content was similar among
      groups. CONCLUSIONS: Both antegrade and retrograde perfusion demonstrated
      excellent functional preservation, at least equivalent to static storage. Initial
      function was superior in the antegrade group, but the retrograde hearts displayed
      better function late after reperfusion. Neither perfused group developed
      significant edema. Machine perfusion preservation is a promising technique for
      improving results of cardiac transplantation.

PMID- 24935335
TI  - Immunosuppressive activity of adipose tissue-derived mesenchymal stem cells in a
      rat model of hind limb allotransplantation.
AB  - Many reports have shown that bone marrow-derived mesenchymal stem cells exhibit
      immunosuppressive effects in allogeneic transplantation. However, few reports
      have evaluated the immunosuppressive properties of adipose tissue-derived
      mesenchymal stem cells (ASCs) in vitro and in vivo. In this study, we
      investigated the immunosuppressive characteristics of ASCs, and investigated
      whether ASCs originating from donor rats prolong allotransplant survival in a rat
      hind limb allotransplantation model. T-cell proliferation stimulated by
      allogeneic stimuli or mitogen with or without ASCs originating from the donor was
      assessed in vitro. The effects of cellular contact or soluble factors on the
      inhibition of T-cell proliferation were also evaluated. In the in vivo study,
      cultured ASCs (1 * 10(5)) that originated from the donor were injected into
      recipient animals intravenously immediately after operation, followed by 1 dose
      per day for 3 consecutive days post-transplantation. When immune rejection
      occurred, the survival time of allotransplants was determined and rejected tissue
      was histologically and immunochemically assessed for determining regulatory T
      cell infiltration. ASCs inhibited the T-cell proliferation stimulated by
      alloantigen or mitogen in a dose-dependent manner, and recipient T cells
      proliferated less in animals treated with ASCs than in controls. Although ASCs
      were separated from T cells, ASCs persisted to elicit a suppressive effect. ASC
      culture supernatants did not inhibit T-cell proliferation; however, supernatants
      obtained from the mixed lymphocyte reaction in the presence of ASCs suppressed T
      cell proliferation. ASCs prolonged allotransplant survival time, reduced
      inflammatory cell infiltration, and induced regulatory T cells. In conclusion,
      ASCs can exhibit in vitro immunosuppressive properties and prolong allotransplant
      survival time in a rat hind limb composite tissue allotransplantation model,
      possibly through the induction of regulatory T cells.

PMID- 24935336
TI  - 1,25(OH)2D3 prolongs islet graft survival by inflammatory inhibition.
AB  - OBJECTIVE: This study aimed to determine the protective effect of 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) against islet graft loss. METHODS:
      Proliferation of tumor necrosis factor (TNF)-alpha-induced macrophages was
      determined in vitro after treatment with different concentrations of 1,25
      (OH)2D3. Intraportal islet transplantation (IPIT) was performed with islets
      harvested from the Sprague-Dawley rats and transplanted to the diabetic rats. The
      transplanted rats were assigned to receive 1,25-(OH)2D3 or propylene glycol
      (control). Islet graft survival; inflammatory cytokine (TNF-alpha and interleukin
      [IL]-1); numbers and percentages of macrophages, CD4(+), and CD8(+) T cells in
      bloods; and expression of nuclear factor (NF)-kappaB and TNF-alpha were analyzed.
      Hematoxylin and eosin staining was performed. RESULTS: We found 100 mg/mL 1,25
      (OH)2D3 per day to have the strongest inhibitory effect on macrophages. Survival
      time of islet grafts significantly increased in the rats receiving 1,25-(OH)2D3.
      There were fewer infiltrated inflammatory cells in both islet graft and adjacent
      tissue in the drug-treated rats with lower serum IL-1 and TNF-alpha. Furthermore,
      percentage of macrophages and expression of p-NF-kappaB p65 and TNF-alpha in
      graft sites were significantly lower in the treated rats. CONCLUSION: Our results
      demonstrated that 1,25(OH)2D3 prolongs islet graft survival by decreasing
      nonspecific inflammation in syngeneic IPIT through inhibiting TNF-alpha/NF-kappaB
      pathway and macrophage infiltration.

PMID- 24935337
TI  - Supplementing mesenchymal stem cells improves the therapeutic effect of
      hematopoietic stem cell transplantation in the treatment of murine systemic lupus
      erythematosus.
AB  - Transplantation of hematopoietic stem cells (HSCs) has been demonstrated to be a
      promising strategy in the treatment of systemic lupus erythematosus (SLE).
      Mesenchymal stem cells (MSCs) support hematopoiesis of HSCs and suppress immune
      response in a dose-dependent manner. Previous study showed that MSCs could
      alleviate the pathologic conditions of MRL/lpr mice (SLE animal model) when
      cotransplanted with bone marrow cells. Here, we investigated whether MSCs could
      improve the therapeutic effect of HSC transplantation in treating MRL/lpr mice in
      a dose-dependent manner. We found that lethally irradiated MRL/lpr mice were
      successfully reconstituted with HSCs alone or with various amounts of MSCs. Mice
      transplanted with HSCs and MSCs in the ratios of 5:1 (HSCs:MSCs) showed less
      transfusion-associated graft-versus-host reaction, steady body weight, and
      improved renal functions when compared with mice transplanted with HSCs only and
      those cotransplanted with MSCs in lower ratios. These results suggest that
      supplementing MSCs can improve the therapeutic effect of HSC transplantation in
      treatment of MRL/lpr mice in a dose-dependent manner. 

PMID- 24935338
TI  - Adult porcine islet isolation using a ductal preservation method and purification
      with a density gradient composed of histidine-tryptophan-ketoglutarate solution
      and iodixanol.
AB  - BACKGROUND: Given the fragility of adult porcine islets, reduction of shearing
      stress in islet purification using histidine-tryptophan-ketoglutarate (HTK)
      solution and iodixanol could be an effective strategy. We examined the effect of
      ductal preservation with HTK solution and an islet purification protocol that
      utilizes HTK solution and iodixanol in adult porcine islet isolation. METHODS:
      Islets were isolated with a modified Ricordi method using adult Prestige World
      Genetics (PWG) and Yucatan pigs. The discontinuous density gradient was composed
      of either HTK solution/iodixanol (n = 23, iodixanol group) or Hank's balanced
      salt solution (HBSS)/Ficoll (n = 17, Ficoll group). In the iodixanol group,
      ductal injection of HTK solution was performed before purification. RESULTS: In
      PWG pigs, significantly higher islet yield after purification (3480 +/- 214.2
      islet equivalent [IEQ]/g, P = .003) and higher recovery rate (85.45% +/- 3.49%, P
      = .0043) were obtained from the HTK/iodixanol group as compared to the
      HBSS/Ficoll group (1905 +/- 323.2 IEQ/g, and 67.22% +/- 4.77%, respectively).
      Similar results were obtained in Yucatan pigs with greater body weight.
      CONCLUSION: Ductal preservation and iodixanol-based islet purification using HTK
      solution improved the yield of adult porcine islet isolation compared to the
      conventional method using HBSS and Ficoll. The results of this study support the
      feasibility of an adult porcine islet isolation protocol using HTK solution and
      iodixanol, which have the favorable physical properties.

PMID- 24935339
TI  - In vitro differentiation of human liver-derived stem cells with mesenchymal
      characteristics into immature hepatocyte-like cells.
AB  - Liver transplantation is severely limited by donor shortage although it is the
      only effective treatment for end-stage liver disease. So the best alternative is
      hepatocyte transplantation. For obtaining human hepatocytes, some stem cells
      originating from extrahepatic or intraheptic tissues have been isolated and
      characterized. Previously we have reported that human liver-derived stem cells
      (HLSCs) could be isolated and expanded from donated livers unsuitable for
      transplantation; they expressed some markers of mesenchymal stem cells but
      neither hematopoietic nor oval cells. In this study, we isolated and expanded
      HLSCs with mesenchymal characteristics from another adult human liver. They
      showed mesenchymal morphology and grew well under serum condition similar to our
      previous reports. Also, they expressed some markers of mesenchymal stem cells,
      such as CD44, CD73, CD90, and CD105, through fluorescence-activated cell sorting
      analysis. When HLSCs were sequentially exposed to fibroblast growth factor-1 (FGF
      1), FGF-4, and hepatocyte growth factor (HGF) followed by FGF-4, HGF, oncostatin
      M, and dexamethasone, they became round or polygonal, and expressed some hepatic
      markers such as albumin and alpha1-antitrypsin in the gene or protein level.
      Also, they showed urea synthesis activity 7 days after treatment of FGF-4, HGF,
      oncostatin M, and dexamethasone. These results provided that HLSCs would be a
      useful cell source in the field of regenerative medicine as well as liver cell
      biology. 

PMID- 24935340
TI  - B7-H1 inhibits T cell proliferation through MHC class II in human mesenchymal
      stem cells.
AB  - B7-H1 on mesenchymal stem cells (MSCs) is known to modulate immune response.
      However, its expression pattern and exact immunomodulatory mechanism are unclear.
      In this study, we examined the immunomodulatory mechanism through the expression
      pattern of B7-H1 and major histocompatibility complex class II in various MSCs.
      Human bone marrow, adipose tissue, and cord blood MSCs were isolated and
      cultured. B7-H1, HLA-ABC, and HLA-DR expression on MSCs by interferon-gamma (IFN
      gamma) was detected time-dependently by flow cytometry. The inhibitory effect of
      MSCs on T lymphocytes was observed in phytohemagglutinin antigen-induced T cell
      proliferation assay. The expression of B7-H1 was rapidly induced, but the
      expression of HLA-DR was induced at 48 hours after IFN-gamma treatment. The
      inhibitory effect of MSCs on T cell proliferation could be restored when the anti
      B7-H1 monoclonal antibody was used to block the B7-H1, or when the HLA-DRalpha
      small interfering RNA was used to interfere with its expression. These results
      show that MSCs could inhibit the T cell proliferation and activation by B7-H1
      depending on the presence of HLA-DR. Therefore, MSCs would have a strong effect
      on immune diseases such as graft-versus-host disease and autoimmune diseases when
      MSCs are primed with IFN-gamma 48 hours before transplantation. 

PMID- 24935341
TI  - Effect of inhibiting the signal of mammalian target of rapamycin on memory T
      cells.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) signaling is crucial to the
      activation and proliferation of T cells. Memory T cells can significantly hinder
      the induction of transplant tolerance. Resent research demonstrates that mTOR
      signaling regulates the survival and function of memory T cells. MATERIALS AND
      METHODS: Naive T cells were adoptively transferred to Rag(-/-) mice to generate
      similar memory T cells that undergo homeostatic proliferation. These memory T
      cells were then used to examine the effect of mTOR inhibition on the function of
      memory T cells. The effect of inhibiting mTOR signaling on the apoptosis of
      memory T cells was also examined. RESULTS: Quantitative reverse-transcription
      polymerase chain reaction analysis showed that the expression of mTOR signaling
      was substantially lower in memory T cells. The levels of interferon-gamma,
      interleukin (IL)-2, IL-4, and IL-10 decreased after mTOR inhibition; the
      expression of Bcl-2 increased in memory CD8(+) T cells and decreased in memory
      CD4(+) T cells; and Bax increased in memory CD4(+) T cells and decreased in
      memory CD8(+) T cells. Memory CD4(+) T cells were more sensitive to apoptotic
      cell death in this model after mTOR inhibition. Memory CD8(+) T cells were not
      affected by mTOR inhibition. CONCLUSIONS: mTOR was crucial to homeostatic
      proliferation-induced memory T cells. The critical mechanisms of mTOR signaling
      inhibition are suppressed the functions of memory T cells and promoted the
      apoptosis of memory CD4(+) T cells.

PMID- 24935342
TI  - Rapid large-scale culturing of microencapsulated hepatocytes: a promising
      approach for cell-based hepatic support.
AB  - INTRODUCTION: The efficacy of any bioartificial liver device requires both rapid
      production and proper bioactivity of the cells for the bioreactor. The goal of
      this study was to observe the effect of spinner speed and cell density on the
      proliferation of microencapsulated immortalized human hepatocytes (HepLL) and
      human hepatoma (HepG2) cells. MATERIALS AND METHODS: Alginate-chitosan
      microcapsulated HepG2 and HepLL cells were randomly divided into 2 groups, and
      each group was further divided into 8 subgroups according to embedded cell
      density and spinner speed. The growth, metabolism, and functions of the
      encapsulated cells in each group were evaluated. RESULTS: In each group, the cell
      number, ammonium removal, albumin synthesis, and diazepam clearance increased
      significantly with the spinner speed, whereas embedded cell density had no
      impact. Albumin synthesis, removal of ammonium, and diazepam clearance were
      significantly higher in the microencapsulated HepLL groups than in HepG2 cells at
      any time point, without any significant difference in cell numbers. CONCLUSIONS:
      Spinner culture significantly promoted microencapsulated HepLL and HepG2 cell
      bioactivity. Wrapped cells had optimal function on day 10 in rolling culture
      groups. These data show that HepLL cells would be a promising candidate for cell
      based liver support therapy.

PMID- 24935343
TI  - Patterns of nucleotide diversity and phenotypes of two domestication related
      genes (OsC1 and Wx) in indigenous rice varieties in Northeast India.
AB  - BACKGROUND: During the domestication of crops, individual plants with traits
      desirable for human needs have been selected from their wild progenitors.
      Consequently, genetic and nucleotide diversity of genes associated with these
      selected traits in crop plants are expected to be lower than their wild
      progenitors. In the present study, we surveyed the pattern of nucleotide
      diversity of two selected trait specific genes, Wx and OsC1, which regulate
      amylose content and apiculus coloration respectively in cultivated rice
      varieties. The analyzed samples were collected from a wide geographic area in
      Northeast (NE) India, and included contrasting phenotypes considered to be
      associated with selected genes, namely glutinous and nonglutinous grains and
      colored and colorless apiculus. RESULTS: No statistically significant selection
      signatures were detected in both Wx and OsC1gene sequences. However, low level of
      selection that varied across the length of each gene was evident. The glutinous
      type varieties showed higher levels of nucleotide diversity at the Wx locus
      (pitot = 0.0053) than nonglutinous type varieties (pitot = 0.0043). The OsC1 gene
      revealed low levels of selection among the colorless apiculus varieties with
      lower nucleotide diversity (pitot = 0.0010) than in the colored apiculus
      varieties (pitot = 0.0023). CONCLUSIONS: The results revealed that functional
      mutations at Wx and OsC1genes considered to be associated with specific
      phenotypes do not necessarily correspond to the phenotypes in indigenous rice
      varieties in NE India. This suggests that other than previously reported genomic
      regions may also be involved in determination of these phenotypes.

PMID- 24935344
TI  - Advancing the application of systems thinking in health: why cure crowds out
      prevention.
AB  - INTRODUCTION: This paper presents a system dynamics computer simulation model to
      illustrate unintended consequences of apparently rational allocations to curative
      and preventive services. METHODS: A modeled population is subject to only two
      diseases. Disease A is a curable disease that can be shortened by curative care.
      Disease B is an instantly fatal but preventable disease. Curative care workers
      are financed by public spending and private fees to cure disease A. Non-personal,
      preventive services are delivered by public health workers supported solely by
      public spending to prevent disease B. Each type of worker tries to tilt the
      balance of government spending towards their interests. Their influence on the
      government is proportional to their accumulated revenue. RESULTS: The model
      demonstrates effects on lost disability-adjusted life years and costs over the
      course of several epidemics of each disease. Policy interventions are tested
      including: i) an outside donor rationally donates extra money to each type of
      disease precisely in proportion to the size of epidemics of each disease; ii)
      lobbying is eliminated; iii) fees for personal health services are eliminated;
      iv) the government continually rebalances the funding for prevention by ring
      fencing it to protect it from lobbying.The model exhibits a "spend more get less"
      equilibrium in which higher revenue by the curative sector is used to influence
      government allocations away from prevention towards cure. Spending more on curing
      disease A leads paradoxically to a higher overall disease burden of unprevented
      cases of disease B. This paradoxical behavior of the model can be stopped by
      eliminating lobbying, eliminating fees for curative services, and ring-fencing
      public health funding. CONCLUSIONS: We have created an artificial system as a
      laboratory to gain insights about the trade-offs between curative and preventive
      health allocations, and the effect of indicative policy interventions. The
      underlying dynamics of this artificial system resemble features of modern health
      systems where a self-perpetuating industry has grown up around disease-specific
      curative programs like HIV/AIDS or malaria. The model shows how the growth of
      curative care services can crowd both fiscal and policy space for the practice of
      population level prevention work, requiring dramatic interventions to overcome
      these trends.

PMID- 24935346
TI  - The impact of smoking on HPV infection and the development of anogenital warts.
AB  - PURPOSE: The worldwide prevalence of human papillomavirus (HPV) infection is
      estimated at 9-13 %. Persistent infection can lead to the development of
      malignant and nonmalignant diseases. Low-risk HPV types are mostly associated
      with benign lesions such as anogenital warts. In the present systematic review,
      we examined the impact of smoking on HPV infection and the development of
      anogenital warts, respectively. METHODS: A systematic literature search was
      performed using MEDLINE database for peer-reviewed articles published from
      January 01, 1985 to November 30, 2013. Pooled rates of HPV prevalence were
      compared using the chi (2) test. RESULTS: In both genders, smoking is associated
      with higher incidence and prevalence rates for HPV infection, whereas the latter
      responds to a dose-effect relationship. The overall HPV prevalence for smoking
      patients was 48.2 versus 37. 5 % for nonsmoking patients (p < 0.001) (odds ratio
      (OR) = 1.5, 95 % confidence interval (CI) 1.4-1.7). Smoking does also increase
      persistence rates for high-risk HPV infection, while this correlation is
      debatable for low-risk HPV. The incidence and recurrence rates of anogenital
      warts are significantly increased in smokers. CONCLUSIONS: Most current data
      demonstrate an association between smoking, increased anogenital HPV infection,
      and development of anogenital warts. These data add to the long list of reasons
      for making smoking cessation a keystone of patient health.

PMID- 24935347
TI  - Target volume geometric change and/or deviation from the cranium during
      fractionated stereotactic radiotherapy for brain metastases: potential pitfalls
      in image guidance based on bony anatomy alignment.
AB  - INTRODUCTION: This study sought to evaluate the potential geometrical change
      and/or displacement of the target relative to the cranium during fractionated
      stereotactic radiotherapy (FSRT) for treating newly developed brain metastases.
      METHODS: For 16 patients with 21 lesions treated with image-guided frameless FSRT
      in 5 or 10 fractions using a 6-degree-of-freedom image guidance system-integrated
      platform, the unenhanced computed tomography or T2-weighted magnetic resonance
      images acquired until the completion of FSRT were fused to the planning image
      datasets for comparison. Significant change was defined as >=3-mm change in the
      tumour diameter or displacement of the tumour centroid. RESULTS: FSRT was started
      1 day after planning image acquisition. Tumour shrinkage, deviation and both were
      observed in 2, 1 and 1 of the 21 lesions, respectively, over a period of 7-13
      days. Tumour shrinkage or deviation resulted in an increase or decrease in the
      marginal dose to the tumour, respectively, and a substantial increase in the
      irradiated volume for the surrounding tissue irrespective of the pattern of
      alteration. No obvious differences in the clinical and treatment characteristics
      were noted among the populations with or without significant changes in tumour
      volume or position. CONCLUSION: Target deformity and/or deviation can
      unexpectedly occur even during relatively short-course FSRT, inevitably leading
      to a gradual discrepancy between the planned and actually delivered doses to the
      tumour and surrounding tissue. To appropriately weigh the treatment outcome
      against the planned dose distribution, target deformity and/or deviation should
      also be considered in addition to the immobilisation accuracy, as image guidance
      with bony anatomy alignment does not necessarily guarantee accurate target
      localisation until completion of FSRT.

PMID- 24935349
TI  - Re: Review article: elevated troponin: diagnostic gold or fool's gold?

PMID- 24935348
TI  - Comparison of clinical and biochemical markers of dehydration with the clinical
      dehydration scale in children: a case comparison trial.
AB  - BACKGROUND: The clinical dehydration scale (CDS) is a quick, easy-to-use tool
      with 4 clinical items and a score of 1-8 that serves to classify dehydration in
      children with gastroenteritis as no, some or moderate/severe dehydration. Studies
      validating the CDS (Friedman JN) with a comparison group remain elusive. We
      hypothesized that the CDS correlates with a wide spectrum of established markers
      of dehydration, making it an appropriate and easy-to-use clinical tool. METHODS:
      This study was designed as a prospective double-cohort trial in a single tertiary
      care center. Children with diarrhea and vomiting, who clinically required
      intravenous fluids for rehydration, were compared with minor trauma patients who
      required intravenous needling for conscious sedation. We compared the CDS with
      clinical and urinary markers (urinary electrolytes, proteins, ratios and
      fractional excretions) for dehydration in both groups using receiver operating
      characteristic (ROC) curves to determine the area under the curve (AUC). RESULTS:
      We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105)
      in the comparison group. Median age was 32 months (range 3-214) in the
      dehydration and 96 months (range 2.6-214 months, p < 0.0001) in the trauma group.
      Median CDS was 3 (range 0-8) within the dehydration group and 0 in the comparison
      group (p < 0.0001). The following parameters were statistically significant (p <
      0.05) between the comparison group and the dehydrated group: difference in heart
      rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium,
      fractional sodium excretion, serum bicarbonate, and creatinine measurements. The
      best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798
      and 0.821, respectively). CDS was most closely correlated with serum bicarbonate
      (Pearson r = -0.3696, p = 0.002). CONCLUSION: Although serum bicarbonate is not
      the gold standard for dehydration, this study provides further evidence for the
      usefulness of the CDS as a dehydration marker in children. TRIAL REGISTRATION:
      Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007.

PMID- 24935350
TI  - Somatostatin therapy protects porcine livers in small-for-size liver
      transplantation.
AB  - Small-for-size (SFS) injury occurs in partial liver transplantation due to
      several factors, including excessive portal inflow and insufficient intragraft
      responses. We aim to determine the role somatostatin plays in reducing portal
      hyperperfusion and preventing the cascade of deleterious events produced in small
      grafts. A porcine model of 20% liver transplantation is performed.
      Perioperatively treated recipients receive somatostatin and untreated controls
      standard intravenous fluids. Recipients are followed for up to 5 days. In vitro
      studies are also performed to determine direct protective effects of somatostatin
      on hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). At
      reperfusion, portal vein flow (PVF) per gram of tissue increased fourfold in
      untreated animals versus approximately threefold among treated recipients (p =
      0.033). Postoperatively, markers of hepatocellular, SEC and HSC injury were
      improved among treated animals. Hepatic regeneration occurred in a slower but
      more orderly fashion among treated grafts; functional recovery was also
      significantly better. In vitro studies revealed that somatostatin directly
      reduces HSC activation, though no direct effect on SEC was found. In SFS
      transplantation, somatostatin reduces PVF and protects SEC in the critical
      postreperfusion period. Somatostatin also exerts a direct cytoprotective effect
      on HSC, independent of changes in PVF. 

PMID- 24935351
TI  - Using real-time impedance-based assays to monitor the effects of fibroblast
      derived media on the adhesion, proliferation, migration and invasion of colon
      cancer cells.
AB  - Increasing our knowledge of the mechanisms regulating cell proliferation,
      migration and invasion are central to understanding tumour progression and
      metastasis. The local tumour microenvironment contributes to the transformed
      phenotype in cancer by providing specific environmental cues that alter the cells
      behaviour and promotes metastasis. Fibroblasts have a strong association with
      cancer and in recent times there has been some emphasis in designing novel
      therapeutic strategies that alter fibroblast behaviour in the tumour
      microenvironment. Fibroblasts produce growth factors, chemokines and many of the
      proteins laid down in the ECM (extracellular matrix) that promote angiogenesis,
      inflammation and tumour progression. In this study, we use a label-free RTCA
      (real-time cell analysis) platform (xCELLigence) to investigate how media derived
      from human fibroblasts alters cancer cell behaviour. We used a series of
      complimentary and novel experimental approaches to show HCT116 cells adhere,
      proliferate and migrate significantly faster in the presence of media from human
      fibroblasts. As well as this, we used the xCELLigence CIM-plates system to show
      that HCT116 cells invade matrigel layers aggressively when migrating towards
      media derived from human fibroblasts. These data strongly suggest that
      fibroblasts have the ability to increase the migratory and invasive properties of
      HCT116 cells. This is the first study that provides real-time data on fibroblast
      mediated migration and invasion kinetics of colon cancer cells. 

PMID- 24935352
TI  - Telaprevir raises the plasma/whole blood ribavirin ratio: trying to come full
      circle on a dangerous relationship.

PMID- 24935354
TI  - Should we target patients with autoimmune diseases for human papillomavirus
      vaccine uptake?
AB  - Human papillomavirus (HPV) is the cause of most cases of cervical cancer
      worldwide. Studies suggest that patients with autoimmune diseases (AD) may be at
      increased risk for persistent HPV infection, cervical dysplasia, and possibly,
      cervical cancer. Despite this heightened risk, and studies demonstrating the
      safety and efficacy of the HPV vaccine in this population, uptake among patients
      with AD, and in the overall population, remains low. A number of studies suggest
      that this may be attributed to lack of patient and provider awareness, no school
      based requirement for vaccination, and a hesitancy to discuss sexually
      transmitted diseases with adolescents. Among patients with AD, access to
      preventive care in general may be reduced. Overall, heightened public health
      efforts are needed to improve HPV vaccination uptake in the entire population and
      among patients with AD who may be at increased risk for persistent infection and
      for cervical dysplasia. 

PMID- 24935355
TI  - Serum microRNA-210 as a predictive biomarker for treatment response and prognosis
      in patients with hepatocellular carcinoma undergoing transarterial
      chemoembolization.
AB  - PURPOSE: To investigate whether serum microRNA-210 (miR-210) level can serve as
      an indicator of prognosis and a predictor of efficacy of transarterial
      chemoembolization in patients with hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Serum miR-210 level was measured in 113 patients with HCC before
      transarterial chemoembolization (t1), 3 days after transarterial
      chemoembolization (t2), and 4 weeks after transarterial chemoembolization (t3)
      and compared with 39 healthy control subjects. The correlations between miR-210
      levels and clinicopathologic factors, tumor responsiveness, and prognosis were
      analyzed. The modified Response Evaluation Criteria in Solid Tumors assessment
      was conducted at t3. RESULTS: A higher mean baseline miR-210 level was observed
      in patients with HCC compared with control subjects (3.69 +/- 2.04 vs 1.08 +/-
      0.45, P < .001). A positive correlation between baseline miR-210 level and tumor
      size (P < .001), vascular invasion (P = .005), tumor differentiation (P = .037),
      and Barcelona Clinic Liver Cancer stage (P < .001) was observed. Elevated
      baseline miR-210 level also served as an independent prognostic factor predicting
      poor overall survival (risk ratio, 2.082; P = .003). Patients who did not respond
      to transarterial chemoembolization had higher baseline miR-210 levels than
      patients who did respond to treatment (4.34 +/- 1.67 vs 3.28 +/- 2.15, P < .001).
      In addition, miR-210 levels increased significantly 4 weeks after transarterial
      chemoembolization in nonresponders (5.79 +/- 2.06 at t3 vs 4.34 +/- 1.67 at t1, P
      < .001), whereas no significant change was observed in responders (3.53 +/- 2.20
      at t3 vs 3.28 +/- 2.15 at t1, P = .116). Lastly, an inverse correlation was
      identified between miR-210 change t1-t3 with the time to radiologic progression
      (P < .001). CONCLUSIONS: Serum miR-210 may represent a novel biomarker for
      predicting efficacy of transarterial chemoembolization and overall survival for
      patients with HCC.

PMID- 24935356
TI  - ERCC1 as a biological marker guiding management in malignant pleural
      mesothelioma.
AB  - BACKGROUND: To determine prognostic value of excision repair cross
      complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM).
      MATERIALS AND METHODS: The study included 60 patients with MPM who were diagnosed
      and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and
      Medical Oncology Department of Erciyes University, Medicine School between 2005
      and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy
      specimens was evaluated. We retrospectively assessed whether there is a
      correlation between ERCC1 and response to anti-neoplastic therapy or survival.
      RESULTS: There were 50 men and 10 women with median age of 62 years (range: 39
      83). Histological type was epithelial mesothelioma in the majority of the cases
      (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received
      radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received
      second-line chemotherapy. In the assessment after therapy, it was found that
      there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%)
      and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean
      OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless
      of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases,
      respectively. The difference was found to be significant (p<0.05). In univariate
      analysis, stage, comorbidity, response to treatment and ERCC1 expression were
      found to be significantly associated with OS (p=0.083; p=0.043; p=0.041;
      p=0.050). In multivariate analysis, response to treatment remained to be
      significant for OS (p=0.005). In univariate and multivariate analyses, response
      to treatment and ERCC1 were found to be significantly associated with DFS
      (p=0.049; p=0.041). CONCLUSIONS: ERCC1 was identified as poor prognostic factor
      in patients with MPM.

PMID- 24935357
TI  - Changes in median ages at death from selected cancer types in relation to HLA
      DRB1/DQB1.
AB  - The median ages at death from cancers between 1985 and 2005 were calculated to
      demonstrate that inherent anticancer mechanisms may be a common pathway for
      different cancers. Seventy-eight patients with gastric, liver and lung cancers,
      were recruited in the solid cancer group. The leukemia group consisted of 31
      patients with three main types of leukemia. The controls were 100 healthy
      individuals. The samples were typed using an HLA-DR/DQ PCR-SSP typing kit. The
      results showed that the median ages at death from all causes were 64.7 years in
      1985 and 70.1 years in 2005. The range of the median ages at death from all
      cancers was similar to the corresponding value for deaths attributed to all
      causes. The frequency of DRB1*03 was 9.6% in the solid cancer group and 3.0% in
      the control group (p<0.05). The frequency of DRB1*04 in the leukemia group were
      significantly lower than that of the control (p<0.05). DRB1*13 and DQB1*06
      frequencies in the leukemia group were significantly higher than those of the
      controls (p<0.05). It is suggested that inherent anti-cancer mechanisms may be a
      common pathway for different cancers and are associated with the immune system
      and HLA.

PMID- 24935358
TI  - Immune and anti-oxidant functions of ethanol extracts of Scutellaria baicalensis
      Georgi in mice bearing U14 cervical cancers.
AB  - BACKGROUND: The objective was to study the effect of Scutellaria baicalensis
      Georgi ethanol extracts (SBGE) on immune and anti-oxidant function in U14 tumor
      bearing mice. MATERIALS AND METHODS: U14 tumor-bearing mice were randomly divided
      into eight groups: a control group, a cyclophosphamide (CTX) group, three dose
      groups of SBGEI (high, medium, low), and three dose groups of SBGEII (high,
      medium, low). After two weeks, the thymus and spleen weight indices of mice
      bearing U14 cervical cancer were calculated. Enzyme linked immunosorbent assays
      (ELISA) was used to determine the levels of serum IL-2, TNF-alpha, IL-8, and
      PCNA. MDA activity and SOD activity in plasma were measured with detection kits.
      RESULTS: In the SBGE groups, thymus weight and spleen weight indices of U14 tumor
      bearing mice were significantly higher than in the control group or CTX group
      (p<0.05). Compared to control group, the levels of serum IL-2 and TNF-alpha in
      U14 tumor-bearing mice increased significantly, whereas the contents of serum IL
      8 and PCNA decreased (p<0.05). The activity of SOD increased with the growing
      dose of SBGE, while the activity of MDA decreased significantly in the higher-
      dose groups of SBGE. CONCLUSIONS: These findings suggested that SBGE, especially
      at high dose, 1000 mg/kg, showed significant immune and anti-oxidant effects in
      U14 tumor-bearing mice, which might be the mechanisms of SBGE inhibition of tumor
      growth.

PMID- 24935360
TI  - Optimization of predictors of Ewing sarcoma cause-specific survival: a population
      study.
AB  - BACKGROUND: This study used receiver operating characteristic curve to analyze
      Surveillance, Epidemiology and End RESULTS (SEER) Ewing sarcoma (ES) outcome
      data. The aim of this study was to identify and optimize ES-specific survival
      prediction models and sources of survival disparities. MATERIALS AND METHODS:
      This study analyzed socio-economic, staging and treatment factors available in
      the SEER database for ES. 1844 patients diagnosed between 1973-2009 were used for
      this study. For the risk modeling, each factor was fitted by a Generalized Linear
      Model to predict the outcome (bone and joint specific death, yes/no). The area
      under the receiver operating characteristic curve (ROC) was computed. Similar
      strata were combined to construct the most parsimonious models. RESULTS: The mean
      follow up time (S.D.) was 74.48 (89.66) months. 36% of the patients were female.
      The mean (S.D.) age was 18.7 (12) years. The SEER staging has the highest ROC
      (S.D.) area of 0.616 (0.032) among the factors tested. We simplified the 4
      layered risk levels (local, regional, distant, un-staged) to a simpler non
      metastatic (I and II) versus metastatic (III) versus un-staged model. The ROC
      area (S.D.) of the 3-tiered model was 0.612 (0.008). Several other biologic
      factors were also predictive of ES-specific survival, but not the socio-economic
      factors tested here. CONCLUSIONS: ROC analysis measured and optimized the
      performance of ES survival prediction models. Optimized models will provide a
      more efficient way to stratify patients for clinical trials.

PMID- 24935359
TI  - Lack of association between high-risk human papillomaviruses and oral squamous
      cell carcinoma in young Japanese patients.
AB  - BACKGROUND: Human papillomaviruses (HPV) may play an important role as one of the
      possible etiologies of oral squamous cell carcinoma (OSCC). The present study
      aimed to investigate the association between HPV and OSCC in young Japanese
      patients by examining the presence of HPV DNA and surrogate markers in OSCC
      tissues. MATERIALS AND METHODS: Forty young patients with OSCC whose surgical
      specimens were available were analyzed and compared with 40 patients randomly
      recruited from a pool of patients aged >40 years. HPV DNA was detected using the
      polymerase chain reaction-based AMPLICOR((r)) HPV test, and surrogate markers of
      HPV infection were analyzed using immunohistochemical techniques to detect
      p16(INK4a) and p53. RESULTS: Only two (5%) young patients and one (2.5%) older
      patient were positive for HPV DNA. p16(INK4a) overexpression was identified in
      six (15%) young patients. p53 staining levels were not high in tissues of most
      young patients (27 patients, 67.5%). HPV DNA status did not significantly
      correlate with p16(INK4a) expression levels. Profiles of increased levels of
      p16(INK4a) expression with diminished levels of p53 staining were not associated
      with the presence of HPV DNA. The combined p53 with p16(INK4a) profiles were
      significantly correlated with alcohol consumption in younger patients (p=0.006).
      CONCLUSIONS: RESULTS of the present study indicate that HPV is less likely to
      cause OSCC in young Japanese patients, and the p16(INK4a) expression level is not
      an appropriate surrogate marker for HPV infection in OSCC.

PMID- 24935353
TI  - Neural and psychological mechanisms underlying compulsive drug seeking habits and
      drug memories--indications for novel treatments of addiction.
AB  - This review discusses the evidence for the hypothesis that the development of
      drug addiction can be understood in terms of interactions between Pavlovian and
      instrumental learning and memory mechanisms in the brain that underlie the
      seeking and taking of drugs. It is argued that these behaviours initially are
      goal-directed, but increasingly become elicited as stimulus-response habits by
      drug-associated conditioned stimuli that are established by Pavlovian
      conditioning. It is further argued that compulsive drug use emerges as the result
      of a loss of prefrontal cortical inhibitory control over drug seeking habits.
      Data are reviewed that indicate these transitions from use to abuse to addiction
      depend upon shifts from ventral to dorsal striatal control over behaviour,
      mediated in part by serial connectivity between the striatum and midbrain
      dopamine systems. Only some individuals lose control over their drug use, and the
      importance of behavioural impulsivity as a vulnerability trait predicting
      stimulant abuse and addiction in animals and humans, together with consideration
      of an emerging neuroendophenotype for addiction are discussed. Finally, the
      potential for developing treatments for addiction is considered in light of the
      neuropsychological advances that are reviewed, including the possibility of
      targeting drug memory reconsolidation and extinction to reduce Pavlovian
      influences on drug seeking as a means of promoting abstinence and preventing
      relapse. 

PMID- 24935361
TI  - Role of concomitant chemoradiation in locally advanced head and neck cancers.
AB  - Standard therapy for advanced head and neck cancer consists of a combination of
      surgery and radiation. However, survival of this patient population has not
      improved during the past 20 years. Many different multimodality treatment
      schedules have been proposed, and chemotherapy is often used with the intent of
      organ preservation. The present study was intended to establish the efficacy of
      concomitant chemoradiation with a single agent carboplatin in advanced head and
      neck cancers.The objectives were to investigate the feasibility of concomitant
      administration of carboplatin, monitor acute toxicity during radiotherapy, and
      determine subacute side effects, such as wound healing following surgery after
      chemoradiotherapy. A prospective study was conducted wherein a total of 40
      patients with stage III and IV squamous cell carcinomas of oral cavity,
      oropharynx, hypopharynx and larynx were enrolled. All patients were treated with
      external beam radiotherapy and weekly carboplatin area under curve (AUC of 5).
      Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total
      dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent
      locoregional disease. Neck dissection was recommended for all patients with neck
      disease showing less than a complete response after chemoradiation. A total of 40
      patients were enrolled of whom 32 were males and 8 were females. Highest
      incidence of cancer was seen in the 5th-6th decades of life with a median age of
      47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed
      by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a
      neck node on presentation of which 40% had N2-N3 nodal status. TNM staging
      revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation
      of acute toxicity revealed that 50% had grade II mucositis, 25% grade III
      mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions,
      65% of patients had grade I thrombocytopenia, and 24% of patients had grade I
      anaemia. After completion of treatment 65% of patients had complete response at
      the primary and regional sites, and 35% of patients had a partial response of
      whom 23% underwent neck dissection and 5% of them underwent salvage surgery at
      the primary site. At the end of one year there were six deaths and four
      recurrences and 70% were free of disease. Concurrent chemoradiation with
      carboplatin provided good locoregional control for locally advanced head and neck
      cancers. This regimen, although toxic, is tolerable with appropriate supportive
      intervention. Primary site conservation is possible in many patients.
      Chemoradiotherapy appears to have an emerging role in the primary management of
      head and neck cancers. 

PMID- 24935362
TI  - Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of
      response of non-small cell lung cancer to chemoradiotherapy.
AB  - BACKGROUND: This study was aimed to establish a novel method to simultaneously
      detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray
      repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class
      III beta-tubulin (TUBB3), and to assess their application in the clinic for
      prediction of response of non-small cell lung cancer (NSCLC) to
      chemoradiotherapy. MATERIALS AND METHODS: We have designed four gene molecular
      beacon (MB) probes for multiplex quantitative real-time polymerase chain
      reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin
      embedded specimens from 50 patients with advanced or metastatic carcinomas.
      Twenty one NSCLC patients receiving cisplatin- based first-line treatment were
      analyzed. RESULTS: These molecular beacon probes could specially bind to their
      target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA
      levels were found to have apparently higher response rates to chemoradiotherapy
      compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The
      TS gene expression level was not significantly associated with chemotherapy
      response (p>0.05). CONCLUSIONS: A method of simultaneously detecting four
      molecular markers was successfully established and applied for evaluation of
      chemoradiotherapy response. It may be a useful tool in personalized cancer
      therapy.

PMID- 24935363
TI  - Etoposide-cisplatin alternating with vinorelbine-cisplatin versus etoposide
      cisplatin alone in patients with extensive disease combined with small cell lung
      cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of alternating
      etoposide-cisplatin and vinorelbine-cisplatin (EP-NP) compared with an etoposide
      cisplatin (EP) regimen for advanced combined small cell carcinomas. MATERIALS AND
      METHODS: Histologically confirmed combined small cell carcinoma patients who met
      the inclusion criteria were randomly assigned (1:1) into either the EP-NP setting
      (group A) or the EP setting (group B). The primary endpoint was progression-free
      survival in patients who received at least one dose of treatment. RESULTS: Eighty
      two patients entered into this trial, 42 in group A and 40 in group B. The
      objective response rates in group A and group B were 42.9% and 32.5%,
      respectively (p=0.334). Survival analysis showed that median progression-free
      survival was 6.1 months in group A, which was significantly longer than the 4.1
      months in group B (p=0.041). However, as to overall survival, no significant
      difference was found between the two groups (11.0 vs 10.1 months in groups A and
      B, respectively, p=0.545). No unexpected side effects were observed in either
      group. CONCLUSIONS: The EP-NP regimen for combined small cell carcinomas
      prolonged progression- free survival compared with the EP regimen. Further
      clinical investigations are warranted.

PMID- 24935364
TI  - Lack of sunlight exposure influence on primary glioblastoma survival.
AB  - BACKGROUND: The prognosis of primary glioblastoma (GBM) is poor. Approximately
      2/3 of primary brain tumor diagnoses are GBM, of which 95% are primary lesions.
      In this study, we aimed to evaluate whether more sunlight exposure has an effect
      on survival of patients with primary GBM. MATERIALS AND METHODS: A total of 111
      patients with primary GBM were enrolled from Kayseri in inner Anatolia which has
      a cold climate (n: 40) and Mersin in Mediterranean region with a warm climate and
      more sunlight exposure (n: 71). The patients with primary GBM were divided into
      two groups as Kayseri and Mersin and compared for progression free survival (PFS)
      and overall survival (OS). RESULTS: The PFS values were 7.0 and 4.7 months for
      Kayseri and Mersin groups, respectively (p=0.10) and the respective OS values
      were 13.3 and 9.4 months (p=0.13). We did not found any significant difference
      regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant
      chemoradiotherapy and palliative chemotherapy between the groups. CONCLUSIONS: We
      found that more sunlight exposure had no impact on prognosis of patients with
      primary GBM, adding inconsistency to the literature about the relationship
      between sunlight and GBM.

PMID- 24935365
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis
      of lymphoma.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of
      lung cancer and benign disorders. However, the utility of EBUS-TBNA in the
      diagnosis of mediastinal lymphomas is unclear. The aim of this study was to
      determine the diagnostic value of EBUS-TBNA in patients with suspected lymphoma.
      MATERIALS AND METHODS: Sixty-eight patients with isolated mediastinal
      lymphadenopathy and suspected of lymphoma were included in the study. EBUS-TBNA
      was performed on outpatients under moderate sedation. The sensitivity,
      specificity, negative predictive value and diagnostic accuracy of EBUS-TBNA were
      calculated. RESULTS: Sixty-four patients were diagnosed by EBUS-TBNA, but four
      patients with non-diagnostic EBUS-TBNA required surgical procedures. Thirty-five
      (51.5%) patients had sarcoidosis, six (8.8%) had reactive lymphadenopathy, nine
      (13.3%) had tuberculosis, one (1.5%) had squamous cell carcinoma, two (2.9%) had
      sarcoma and fifteen (22%) had lymphoma (follicular center cell, large B-cell
      primary, and Hodgkin lymphomas in three, two, and ten, respectively). Of the 15
      lymphoma patients, thirteen were diagnosed by EBUS and two by thoracotomy and
      mediastinoscopy. The sensitivity, specificity, negative predictive value, and
      diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma were calculated as
      86.7%, 100%, 96.4%, and 97%, respectively. CONCLUSIONS: EBUS-TBNA can be employed
      in the diagnosis of mediastinal lymphoma, instead of more invasive surgical
      procedures.

PMID- 24935366
TI  - Histopathologic characterization of prostate diseases in Madinah, Saudi Arabia.
AB  - AIMS: To delineate the histopathological pattern of prostate diseases and to
      highlight age variations in prostate specific antigen (PSA) values and
      histopathological features. MATERIALS AND METHODS: A retrospective review was
      made of all prostate biopsy reports seen between January 2006 and December 2013
      at the King Fahad Hospital, Madinah, Saudi Arabia. Prostate lesions were
      tabulated and classified into benign and malignant groups. Histological scoring
      of adenocarcinomas was accomplished using the Gleason system. PSA values were
      correlated with Gleason scores. RESULTS: Of 417 prostate lesions reviewed, 343
      (82.3%) were benign and 74 (17.7%) were malignant, giving a benign to malignant
      ratio of 4.6:1. Benign prostatic hyperplasia (both with and without inflammation)
      was the commonest prostatic lesion and accounted for 80.3% of all cases and 97.6%
      of all benign cases. The age range was 20 to 97 years with a mean of 69.2 years
      and a peak age group at 70-79 years. Seventy one cases of adenocarcinoma
      accounted for 95.9% of the total of 74 malignant tumors. It showed an age range
      of 44 to 95 years, a mean age of 70.9 years and peak prevalence in the 80-89 year
      age group. Gleason score seven was the most frequent (39.4%) in occurrence. Most
      adenocarcinomas, 41 cases (57.7%), were moderately differentiated (Gleason score
      of 5-7). PSA values ranged widely between 16-1,865 ng/ml with a mean of 363.4
      ng/ml. Elevated PSA (>100 ng/ml) levels were found in 53 (81.6%) patients. There
      was a statistically significant positive correlation between serum PSA level and
      Gleason score (p=0.0304). CONCLUSIONS: Prostatic lesions constitute a significant
      source of morbidity among adult males in Madinah. Benign prostatic hyperplasia
      was the commonest benign prostatic lesion and adenocarcinoma was the commonest
      histological subtype of prostatic cancer.

PMID- 24935367
TI  - Quality of life of male spouse caregivers for breast cancer patients in China.
AB  - BACKGROUND: The aim of this study was to describe the characteristics of male
      spouse caregivers of breast cancer patients in China, assess their quality of
      life (QOL), and investigate the influencing factors. MATERIALS AND METHODS: A
      total of 243 breast cancer patient-spouse caregiver dyads were recruited from
      four hospitals in Shanxi and Anhui province of China. A cross-sectional design
      was applied to collect data and the Chinese version of the Medical Outcomes Study
      36-item Short Form (SF-36) was used to measure caregivers' QOL, and the Chinese
      version of M.D. Anderson Symptom Inventory (MDASI-C) was applied to measure
      patient symptom severity and interference. Pearson's correlation was used to
      examine the correlations between caregiver burden and QOL. The multiple
      regression analysis was used to determine the most predictive factors influencing
      QOL. RESULTS: The scores of all SF-36 scales were above 50.0, which were much
      lower than that of general mainland Chinese males. Mental QOL was significantly
      worse than physical QOL. Spouses demographic characteristics, caregiving-related
      variables and patient symptoms were related to spouse QOL. Caregiver burden has a
      negative relationship with QOL. CONCLUSIONS: A decrease in life events and
      patient symptoms, as well as increase in spouse sleeping time and family income,
      ought to improve QOL.

PMID- 24935368
TI  - Association of matrix metalloproteinase (MMP)-2 and -9 expression with extra
      gastrointestinal stromal tumor metastasis.
AB  - Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in
      invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors
      (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9
      expression in EGIST tissue samples for association with clinicopathological data
      from the patients. Twenty-one surgical EGIST tissue specimens were collected for
      analysis of MMP-2 and MMP- 9 expression using immunohistochemistry. MMP-2 and MMP
      9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas
      they were only expressed in 75% of the spindle cell type, although there was no
      statistically significant difference (p>0.05). Expression of MMP-2 and MMP-9
      proteins was associated with tumor size, mitotic rate, tumor necrosis, and
      distant metastasis (p<0.05). MMP-2 expression was linked with MMP-9 levels
      (p<0.05). However, there was no correlation between MMP-9 expression and age,
      sex, primary site, or cell morphology in any of these 21 EGIST patients (p>0.05).
      Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of
      EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9
      expression with advanced EGIST behavior.

PMID- 24935369
TI  - Clinical characteristics of gynecologic cancer patients who respond to salvage
      treatment with Lingzhi.
AB  - Lingzhi or Ganoderma lucidum is a popular medicinal mushroom used as a health
      promotion herb in China and other Asian countries for thousands of years. There
      have many previous studies about the anti-cancer effects of lingzhi especially in
      vitro. The present study reports the clinical data of 5 gynecologic cancer
      patients who achieved stability in the disease after ingestion of lingzhi in the
      form of fruit body water extract and spores in a salvage setting. This report has
      been written to enhance the data describing the effect of lingzhi in cancer
      patients.

PMID- 24935370
TI  - Local cervical immunity in women with low-grade squamous intraepithelial lesions
      and immune responses after abrasion.
AB  - Minor trauma to the uterine cervix is supposed to induce local immunity to
      prevent cervical lesions caused by human papillomavirus (HPV) infection. This
      study aimed to investigate the local cervical immunity in women with low grade
      squamous intraepithelial lesion (LSIL) and effects of abrasion after cryosurgery
      or Pap smear. One hundred women with LSIL and known results of HPV detection were
      recruited. HPV positive women were randomly divided according to abrasion into
      cryotherapy and Pap smear observation groups. Cervical tissues and cervico
      vaginal lavage (CVL) were collected at 6 and 12 months after allocation. The
      levels of cytokines at first recruitment were compared with cytokine levels at 6
      months after abrasions. The mRNA of IFN-gamma , TNF-alpha and IL-10 in cervical
      tissues and these cytokines secreted in CVL were determined using real time PCR
      and ELISA, respectively. Anti-HPV16 IgG and IgA antibodies in CVL were assessed
      by western blotting. At first recruitment of women with LSIL (100 cases), IL-10
      mRNA and cytokine in HPV positive group (60 cases) was significantly higher than
      negative group (40 cases). IFN-gamma and TNF-alpha mRNA level in both groups were
      comparable but their secretions in CVL were significantly increased in HPV
      negative group. After abrasion for 6 months in HPV-positive women, all mRNA and
      secreted cytokines were changed, but no significant difference was observed
      between cryotherapy and observation groups. When individuals were compared
      between first recruitment and after abrasion for 6 months, IFN-gamma mRNA and
      anti-HPV16 L1 IgA antibodies were significantly increased in the cryotherapy
      group. The results suggest that modulation of local cervical immunities by
      abrasion might promote different effects in clearance of HPV-related cytological
      abnormalities.

PMID- 24935371
TI  - Predictive role of the neutrophil lymphocyte ratio for invasion with gestational
      trophoblastic disease.
AB  - PURPOSE: The objective of this study was to assess the predictive role of the
      neutrophil/lymphocyte ratio (NLR) for invasion of gestational trophoblastic
      disease (GTD). MATERIALS AND METHODS: A retrospective analysis was conducted on
      127 women who were managed at our clinic for GTD. Of all patients, 8 showed
      invasion according to histological examination. The clinical parameters of
      patients with invasive GTD (Group 1; n=8) were compared with patients who showed
      no invasion (Group 2; n=119). All underwent a prior uterine evacuation and
      followed up by regular assessment of beta-hCG titers. RESULTS: Demographic and
      obstetric history and pre-evacuation hCG levels of the patients showed no
      statistically significantly difference between the groups (p>0.05). The mean
      gestational weeks (GW), size of the GTD and NLR levels were statistically
      significantly higher in the invasive GTD group (p<0.05). Correlations between
      invasion and gestational weeks, size of GTD, post-evacuation chemotherapy and NLR
      were evident. ROC curve analysis demonstrated that GW, size of GTD and NLR may be
      discriminative parameters in predicting invasion of GTD. CONCLUSIONS: To the best
      of our knowledge, this is the first study evaluating the predictive role of NLR
      in invasion of GTD. In conclusion, we think that pretreatment NLR can be used as
      a biomarker of invasion in GTD.

PMID- 24935372
TI  - Association analysis of common genetic variations in MUC5AC gene with the risk of
      non-cardia gastric cancer in a Chinese population.
AB  - Several lines of evidence suggest that genetic variation in MUC5AC gene might
      contribute to the risk of gastric cancer. We conducted a case-control study to
      evaluate the relationship between common genetic variations in MUC5AC gene and
      non-cardia gastric cancer using an LD-based tagSNP approach in Baotou, north
      western China. We genotyped 12 tagSNPs by TaqMan method among 288 cases with non
      cardia gastric cancer and 281 normal controls. Unconditional logistic regression
      was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for
      non-cardia gastric cancer risk in association with alleles, genotypes and
      haplotypes. We observed that the frequencies of rs3793964 C allele and rs11040869
      A allele were significantly lower in cases than in controls. Meanwhile, minor
      allele homozygotes of rs3793964 and rs11040869 were significantly associated with
      a decreased risk of non-cardia gastric cancer when compared with their major
      allele homozygotes. Furthermore, a statistically significantly protective effect
      of rs885454 genotypes on non-cardia gastric cancer was also observed (for CT vs.
      CC: OR=0.581, 95%CI=0.408-0.829; for CT/TT vs. CC: OR=0.623, 95%CI=0.451-0.884).
      Our results indicated that some common genetic variations in the MUC5AC gene
      might have effects on the risk of non-cardia gastric cancer in our studied
      population.

PMID- 24935373
TI  - Association of leptin receptor Lys109Arg and Gln223Arg polymorphisms with
      increased risk of clear cell renal cell carcinoma.
AB  - BACKGROUND: Although roles of genetic polymorphisms of leptin receptor (LEPR)
      gene in several cancers have been documented, the association between
      polymorphisms of LEPR and clear cell renal cell carcinoma (CC-RCC) remains
      unknown. The aim of this study was to explore any relation. MATERIALS AND
      METHODS: The study population consisted of 77 patients with CC-RCC and 161
      healthy control subjects. Polymorphism analyses of Lys109Arg and Gln223Arg were
      performed by direct DNA sequencing and PCR-restriction fragment length
      polymorphism approaches respectively. RESULTS: Comparisons of allelic and
      genotypic frequencies in Lys109Arg and Gln223Arg showed no significant difference
      between the cases and controls. However, when evaluating the combined genotype of
      Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30)
      and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of
      the latter could not be calculated for a value of zero) . Furthermore, the G-G
      haplotype frequency of Lys109Arg and Gln223Arg in the cases was higher (OR=1.68;
      95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in the cases
      were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI
      of the latter could not be calculated for a value of zero). In addition, the
      Lys109Arg A allele was in LD with the Gln223Arg A allele (d'=0.9399) in the CC
      RCC subjects, but not in the controls. CONCLUSIONS: Our data suggest that the
      GG/GG combined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as
      evaluating factors for CC-RCC risk.

PMID- 24935374
TI  - Transcriptional profiles of peripheral blood leukocytes identify patients with
      cholangiocarcinoma and predict outcome.
AB  - Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly
      prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA
      remain elusive. The present study was designed to investigate whether peripheral
      blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic
      test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy
      subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We
      indentified informative PBLs gene expression profiles that could reliably
      distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117
      genes were up regulated and 60 were down regulated. The molecular and cellular
      functions predicted for these CCA specific genes according to the Gene Ontology
      database indicated differential PBL expression of host immune response and tumor
      progression genes (EREG, TGF beta1, CXCL2, CXCL3, IL-8, and VEGFA). The
      expression levels of 9 differentially expressed genes were verified in 36 CCA vs
      20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and
      SERPINB2) computed as "prognostic index" was found to be an independent and
      statistically significant predictor for CCA patient survival. The present study
      shows that CCA PBLs may serve as disease predictive clinically accessible
      surrogates for indentifying expressed genes reflective of CCA disease severity.

PMID- 24935375
TI  - Lack of prognostic value of blood parameters in patients receiving adjuvant
      radiotherapy for breast cancer.
AB  - AIM: To determine prognostic value of blood parameters on overall and progression
      free survival in cases received adjuvant radiotherapy and chemotherapy with
      diagnosis of stage I-III breast cancer. MATERIALS AND METHODS: We retrospectively
      reviewed files of 350 patients with non-metastatic breast cancer who were treated
      in the Radiation Oncology Department of Kayseri Teaching Hospital between 2005
      and 2010. Pretreatment white blood cell (WBC), neutrophil, monocyte, basophil and
      eosinophil counts, and the neutrophil/lymphocyte ratio (NLR) and platelet
      lymphocyte ratio (PLR) were recorded. The relationship between
      clinicopathological findings and blood parameters was assessed. RESULTS: Overall,
      344 women and 6 men were recruited. Median age was 55.3 +/- 0.3 years (range: 22
      86). Of the cases, 243 (61.4%) received radiotherapy while 329 (94.3%), received
      chemotherapy and 215 (61.4%) received hormone therapy. Mean overall survival (OS)
      and progression-free survival (PFS) was 84.4 and 78.8 months, respectively.
      During follow-up, 48 patients died due to either disease- related or non-related
      causes. Local recurrence was detected in 14 cases, while distant metastasis was
      noted in 45 cases. In univariate analysis, age, pathology, perinodal invasion
      were significantly associated with overall survival, whereas gender, stage and
      hormone therapy were significantly associated with progression-free survival. In
      multivariate analysis, histopathological diagnosis (OR: 0.3; 95%: 0.1-0.7;
      p=0.006) and perinodal invasion (OR: 0.1; 95% CI: 0.1-1.3; p=0.026) were
      significantly associated with overall survival, whereas tumor stage (OR: 2.1; 95%
      CI: 0.0-0.7; p=0.014) and hormone therapy (OR: 2.1; 95%: 1.2-3.8; p=0.010) were
      significantly associated with progression-free survival. CONCLUSIONS: It was
      found that serum inflammatory markers including WBC, neutrophil, lymphocyte and
      monocyte counts, and NLR and PLR had no effect on prognosis in patients with
      breast cancer who underwent surgery and received adjuvant radiotherapy and
      chemotherapy.

PMID- 24935376
TI  - Relationship of body mass index with prognosis in breast cancer patients treated
      with adjuvant radiotherapy and chemotherapy.
AB  - BACKGROUND: The aim of this study was to investigate the relationship of body
      mass index with overall and progression-free survival as well as other prognostic
      factors of breast cancer in patients with non-metastatic breast cancer. MATERIALS
      AND METHODS: We retrospectively reviewed 456 patients diagnosed with breast
      cancer in the Radiation Oncology department of Kayseri Teaching Hospital between
      2005 and 2013. We investigated relationship of body mass index with prognosis and
      other prognostic factors. RESULTS: The study included 456 patients (447 women and
      9 men). Mean age at presentation was 55.6 years. Of the cases, 96.9% underwent
      modified radical mastectomy and 95.0% received chemotherapy, while 82.4% received
      radiotherapy and 60.0% were given hormone therapy. Body mass index was >25
      mg/kg(2) in 343 cases. Five- and 10-years overall survival rates were 77% and 58%
      whereas progression-free survival rates were 65% and 49%, respectively. In
      univariate analyses, factors including stage (p=0.046), tumor diameter (p=0.001),
      lymph node metastasis (p=0.006) and body mass index (p=0.030) were found to be
      significantly associated with overall survival, while perinodal involvement was
      found to be significantly associated with progression-free survival (p=0.018). In
      multivariate analysis, stage (p=0.032; OR: 3.8; 95% CI: 1.1-13), tumor diameter
      (p<0.000; OR: 0.0; 95% CI: 0.0-0.3), lymph node metastasis (p=0.005; OR: 0.0; 95%
      CI: 0.0-0.5) and BMI (p=0.027; OR: 0.02; 95% CI: 0.0-0.8) remained as
      significantly associated with OS. CONCLUSIONS: In our study, it was seen that
      overall survival time was shorter in underweight and obese patients when compared
      to normal weight patients.

PMID- 24935377
TI  - Influence of curcumin on HOTAIR-mediated migration of human renal cell carcinoma
      cells.
AB  - BACKGROUND: This study investigated the influence of curcumin on HOX transcript
      antisense RNA (HOTAIR)- mediated migration of cultured renal cell carcinoma (RCC)
      cells. MATERIALS AND METHODS: Five RCC cell lines (769-P, 769-P-vector, 769-P
      HOTAIR, 786-0, and Kert-3 ) were maintained in vitro. The expression of HOTAIR
      mRNA was determined by quantitative real-time PCR and cell migration was measured
      by transwell migration assay. The effects of different concentrations of curcumin
      (0 to 80 MUmol/L) on cell proliferation was determined by the CCK-8 assay and
      influence of non-toxic levels (0 to 10 MUM) on the migration of RCC cells was
      also determined. RESULTS: Comparison of the 5 cell lines indicated a correlation
      between HOTAIR mRNA expression and cell migration. In particular, the migration
      of 769-P-HOTAIR cells was significantly higher than that of 769-P-vector cells.
      Curcumin at 2.5-10 MUM had no evident toxicity against RCC cells, but inhibited
      cell migration in a concentration-dependent manner. CONCLUSIONS: HOTAIR
      expression is correlated with the migration of RCC cells, and HOTAIR may be
      involved in the curcumin-induced inhibition of RCC metastasis.

PMID- 24935378
TI  - miR-186 regulates glycolysis through Glut1 during the formation of cancer
      associated fibroblasts.
AB  - Emerging evidence has suggested that glycolysis is enhanced in cancer-associated
      fibroblasts (CAF), and miR-186 is downregulated during the CAF formation.
      However, it is not clear whether miR-186 is involved in the regulation of
      glycolysis and what the role of miR-186 plays during the CAF formation. In this
      study, quantitative PCR analysises show miR-186 is downregulated during the CAF
      formation. Moreover, miR-186 targets the 3' UTR of Glut1, and its overexpression
      results in the degradation of Glut1 mRNA, which eventually reduces the level of
      Glut1 protein. On the other hand, knockdown of miR-186 increased the expression
      of Glut1. Both time course and dose response experiments also demonstrated that
      the protein and mRNA levels of Glut1 increase during CAF formation, according to
      Western blot and quantitative PCR analyses, respectively. Most importantly,
      besides the regulation on cell cycle progression, miR-186 regulates glucose
      uptake and lactate production which is mediated by Glut1. These observations
      suggest that miR-186 plays important roles in glycolysis regulation as well as
      cell cycle checkpoint activation.

PMID- 24935379
TI  - Use of blood transfusion at the end of life: does it have any effects on survival
      of cancer patients?
AB  - BACKGROUND: Treatment of anemia is an important issue in the palliative care
      setting. Blood transfusion is generally used for this purpose in supportive care.
      However the place of blood transfusion in terminally ill cancer cases is less far
      established. OBJECTIVE: We aimed to outline the use of transfusions and to find
      the impact of blood transfusion on survival in patients with advanced cancer and
      very near to death. DESIGN: Patients dying in 2010-2011 with advanced cancer were
      included in the study. We retrospectively collected the data including age, type
      of cancer, the duration of last hospitalisation, ECOG performance status, Hb
      levels, transfusion history of erythrocytes and platelets, cause and the amount
      of transfusion. The anaemic patients who had transfusion at admission were
      compared with the group who were not transfused. Survival was defined as the time
      between the admission of last hospitalisation period and death. RESULTS: Three
      hundred and ninety eight people with solid tumours died in 2010-2011 in our
      clinic. Ninety percent of the patients had anemia at the time of last
      hospitalisation. One hundred fifty three patients had erythrocyte transfusion at
      admission during the last hospitalisation period (38.4%). In the anaemic
      population the duration of last hospitalisation was longer in patients who had
      erythrocyte transfusion (15 days vs 8 days, p<0.001). CONCLUSIONS: Patients who
      had blood transfusion at the end of life lived significantly longer than the
      anaemic patients who were not transfused. This study remarks that blood
      transfusions should not be withheld from terminal cancer patients in palliative
      care.

PMID- 24935380
TI  - Lactobacillus acidophilus and Lactobacillus crispatus culture supernatants
      downregulate expression of cancer-testis genes in the MDA-MB-231 cell line.
AB  - Lactobacilli are probiotics shown to have antitumor activities. In addition, they
      can regulate gene expression through epigenetic mechanisms. In this study, we
      aimed to assess anti tumor activities of Lactobacillus acidophilus and
      Lactobacillus crispatus on the MDA-MB-231 breast cancer cell line. The effects of
      culture supernatants were determined by MTT [3-(4,5-dimethylthiazol-2-y-2,5
      diphenyltetrazolium bromide] assay. Changes in expression of 5 cancer-testis
      antigens (CTAs), namely AKAP4, ODF4, PIWIL2, RHOXF2 and TSGA10 ,were analyzed by
      quantitative real time RT-PCR. The culture supernatants of the 2 lactobacilli
      inhibited MDA-MB-231 cell proliferation. In addition, transcriptional activity of
      all mentioned CTAs except AKAP4 was significantly decreased after 24 hour
      treatment with culture supernatants. This study shows that Lactobacillus
      acidophilus and Lactobacillus crispatus have antiproliferative activity against
      MDA-MB-231 cells. In addition, these lactobacilli could decrease transcriptional
      activity of 4 CTAs. Previous studies have shown that expression of CTAs is
      epigenetically regulated, so it is possible that lactobacilli cause this
      expression downregulation through epigenetic mechanisms. As expression of CTAs in
      cancers is usually associated with higher grades and poor prognosis,
      downregulation of their expression by lactobacilli may have clinical
      implications.

PMID- 24935381
TI  - Comparison of psychotropic prescriptions between oncology and cardiology
      inpatients: result from a pharmacy database in a teaching hospital in Malaysia.
AB  - OBJECTIVE: To examine the prescription rates in cancer patients of three common
      psychotropic drugs: anxiolytic/ hypnotic, antidepressant and antipsychotic.
      MATERIALS AND METHODS: In this retrospective cohort study, data were extracted
      from the pharmacy database of University Malaya Medical Center (UMMC) responsible
      for dispensing records of patients stored in the pharmacy's Medication Management
      and Use System (Ascribe). We analyzed the use of psychotropics in patients from
      the oncology ward and cardiology from 2008 to 2012. Odds ratios (ORs) were
      adjusted for age, gender and ethnicity. RESULTS: A total of 3,345 oncology
      patients and 8,980 cardiology patients were included. Oncology patients were
      significantly more often prescribed psychotropic drugs (adjusted OR:
      anxiolytic/hypnotic=5.55 (CI: 4.64-6.63); antidepressants=6.08 (CI: 4.83-7.64)
      and antipsychotics=5.41 (CI: 4.17-7.02). Non-Malay female cancer patients were at
      significantly higher risk of anxiolytic/hypnotic use. CONCLUSIONS: Psychotropic
      drugs prescription is common in cancer patients. Anxiolytic/hypnotic prescription
      rates are significantly higher in non-Malay female patients in Malaysia.

PMID- 24935382
TI  - Association between gestational diabetes mellitus and subsequent risk of cancer:
      a systematic review of epidemiological studies.
AB  - PURPOSE: This study aimed at summarizing epidemiological evidence of the
      association between gestational diabetes mellitus (GDM) and subsequent risk of
      cancer. MATERIALS AND METHODS: We searched Medline, Embase, Cancer Lit and CINAHL
      for epidemiological studies published by February 1, 2014 examining the risk of
      cancer in patients with history of GDM using highly inclusive algorithms.
      Information about first author, year of publication, country of study, study
      design, cancer sites, sample sizes, attained age of subjects and methods used for
      determining GDM status were extracted by two researchers and Stata version 11.0
      was used to perform the meta-analysis and estimate the pooled effects. RESULTS: A
      total of 9 articles documented 5 cohort and 4 case- control studies containing
      10,630 cancer cases and 14,608 women with a history of GDM were included in this
      review. Taken together, the pooled odds ratio (OR) between GDM and breast cancer
      risk was 1.01 (0.87-1.17); yet the same pooled ORs of case-control and cohort
      studies were 0.87 (0.71-1.06) and 1.25 (1.00-1.56) respectively. There are
      indications that GDM is strongly associated with higher risk of pancreatic cancer
      (HR=8.68) and hematologic malignancies (HR=4.53), but no relationships were
      detected between GDM and other types of cancer. CONCLUSIONS: Although GDM
      increases the risk of certain types of cancer, these results should be
      interpreted with caution becuase of some methodological flaws. The issue merits
      added investigation and coordinated efforts between researchers, antenatal
      clinics and cancer treatment and registration agencies to help attain better
      understanding.

PMID- 24935383
TI  - An epigenetic mechanism underlying doxorubicin induced EMT in the human BGC-823
      gastric cancer cell.
AB  - The epithelial to mesenchymal transition (EMT) is a key step during embryonic
      morphogenesis and plays an important role in drug resistance and metastasis in
      diverse solid tumors. We previously reported that 48 h treatment of anti-cancer
      drug doxorubicin could induce EMT in human gastric cancer BGC-823 cells. However,
      the long term effects of this transient drug treatment were unknown. In this
      study we found that after 48 h treatment with 0.1 MUg/ml doxorubicin, most cells
      died during next week, while a minor population of cells survived and formed
      colonies. We propagated the surviving cells in drug free medium and found that
      these long term cultured drug survival cells (abbreviated as ltDSCs) retained a
      mesenchymal-like cell morphology, and expressed high levels of EMT-related
      molecules such as vimentin, twist and beta-catenin. The expression of chromatin
      reprogramming factors, Oct4 and c-myc, were also higher in ltDSCs than parental
      cells. We further demonstrated that the protein level of p300 was upregulated in
      ltDSCs, and inhibition of p300 by siRNA suppressed the expression of vimentin.
      Moreover, the ltDSCs had higher colony forming ability and were more drug
      resistant when compared to parental cells. Our results suggested that an
      epigenetic mechanism is involved in the EMT of ltDSCs.

PMID- 24935384
TI  - No association between BRCA1 immunohistochemical expression and tumor grade,
      stage or overall survival in platinum-treated epithelial ovarian cancer patients.
AB  - BACKGROUND: The aim of this work is to assess the frequency of BRCA1 protein
      immunohistochemical (IHC) expression in epithelial ovarian cancer (EOC) and to
      evaluate the association of BRCA1 expression with clinical and pathological
      characteristics and the overall survival (OS) of patients treated with
      postoperative platinum- based chemotherapeutic agents. MATERIALS AND METHODS:
      This retrospective study was conducted on 35 cases of epithelial ovarian cancer
      selected from the files of the Pathology Department, Faculty of Medicine,
      Mansoura University, Egypt. Immunohistochemistry (IHC) was performed for BRCA1
      gene protein. BRCA1 expression was compared to patient's age, tumor histology,
      grade, stage and OS time. Statistical analysis was carried out with the SPSS
      version 16.0 to assess significant associations. RESULTS: BRCA1 nuclear
      expression was detected in 40% of EOC, in which a mild increase in the percentage
      of positive cases was observed with serous histology, stage IV, and grade 3
      carcinomas. There was a significant statistical difference in BRCA1 expression
      with regard to histological subtypes of EOC (p=0.048), but not grade or stage.
      Mean OS and survival rate were slightly better for BRCA1 expressing group, but
      there was no statistically significant difference (p=0.528). CONCLUSIONS: No
      association between BRCA1 immunohistochemical expression and tumor grade, stage
      or overall survival was noted in platinum-treated epithelial ovarian cancer
      patients.

PMID- 24935385
TI  - Assessment of the prognostic value of methylation status and expression levels of
      FHIT, GSTP1 and p16 in non-small cell lung cancer in Egyptian patients.
AB  - BACKGROUND: Methylation of tumor suppressor genes has been investigated in all
      kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular
      markers of malignancy, which can lead to better diagnosis, prognosis and therapy.
      Therefore, the aim of this study was to evaluate the association between gene
      hypermethylation and expression of fragile histidine triad (FHIT), glutathione S
      transferase P1 (GSTP1) and p16 genes and various clinicopathologic
      characteristics in primary non-small cell lung carcinomas (NSCLC). MATERIALS AND
      METHODS: The study included 28 primary non-small cell lung carcinomas, where an
      additional 28 tissue samples taken from apparently normal safety margin
      surrounding the tumors served as controls. Methylation-specific polymerase chain
      reaction (MSP) was performed to analyze the methylation status of FHIT, GSTP1 and
      p16 while their mRNA expression levels were measured using a real-time PCR assay
      with SYBR Green I. RESULTS: The methylation frequencies of the genes tested in
      NSCLC specimens were 53.6% for FHIT, 25% for GSTP1, and 0% for p16, and the risk
      of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the
      risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHIT gene
      showed a highly significant correlation with pathologic stage (p<0.01) and a
      significant correlation with smoking habit and FHIT mRNA expression level
      (p<0.05). In contrast, no correlation was observed between the methylation of
      GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05).
      CONCLUSIONS: RESULTS of the present study suggest that methylation of FHIT is a
      useful biomarker of biologically aggressive disease in patients with NSCLC. FHIT
      methylation may play a role in lung cancer later metastatic stages while GSTP1
      methylation may rather play a role in the early pathogenesis.

PMID- 24935386
TI  - Cancer awareness among university students in Turkey.
AB  - BACKGROUND: One of the most important reasons for the high mortality rates of
      cancer is the low level of awareness, which can lead to a late diagnosis and
      treatments starting too late. Therefore, it is necessary for individuals,
      especially at younger age, to gain awareness and integrate taking the necessary
      precautions into their lifestyle in order to prevent cancer and ensure early
      diagnosis. The aim of this study was to assess the levels of awareness of factors
      for major cancers among students studying in two different campuses of a
      university in the Western Black Sea Region. MATERIALS AND METHODS: This
      descriptive/cross-sectional study was performed between January-March 2014.
      Students studying in the 2013-2014 academic year in a university in the Western
      Black Sea Region in two separate campuses were the subjects. RESULTS: The mean
      age was 21.01 +/- 3.63. While female students (51.2%) were the majority in the
      health sciences campus (74.8%), male students (48.8% ) were the majority in the
      social sciences campus (76.5%). Some 9.6% of the students from the health
      sciences campus and 12.4% of the students from the social sciences campus thought
      that cancer was communicable, while most of the students from both campuses knew
      that smoking caused cancer. It can also be seen that the rate of answering
      questions regarding cancer correctly was higher among students studying in the
      health sciences campus. CONCLUSIONS: It was determined that students who do not
      study at the health sciences campus have insufficient information on cancer,
      cancer symptoms, and the possibility of breast cancer in males and approximately
      half of them regarded obesity as a risk factor for cancer.

PMID- 24935387
TI  - Advantages of laparoscopic abdominoperineal resection for anastomotic recurrence
      of rectal cancer.
AB  - BACKGROUND: Surgery offers the only potential for cure and long-term survival of
      recurrence of rectal cancer. Few studies about laparoscopic recurrent lesion
      resection have been reported. This study was designed to evaluate the safety and
      feasibility of laparoscopic abdomino-perineal resection for anastomotic
      recurrence of rectal cancer. MATERIALS AND METHODS: Data for 42 patients with
      recurrence of rectal cancer were collected retrospectively. Of the 42 patients,
      22 underwent laparoscopic surgery (LR group) and 20 received open surgery (OR
      group). Outcomes between the two groups were compared. RESULTS: Operation time in
      LR group was shorter compared with the OR group (164.6 +/- 27.7 min vs 203.0 +/-
      45.3 min); intra-operative blood loss was 119.7 +/- 44.4 ml and 185.0 +/- 94.0 ml
      in LR group and OR group, respectively (p<0.001); time to first flatus in LR
      group was shorter than in OR group, and the difference was statistically
      significant (2.6 +/- 0.8 days vs 3.1 +/- 0.8 days, p=0.013); hospital stay in the
      LR and OR groups was 8.6 +/- 1.3 days and 9.8 +/- 2.2 days; 3-year survival rates
      in the LR and OR groups were 44.4% and 42.8% (p=0.915) and the 3-year disease
      free survival rates were 36.4% and 30.0%, respectively (p=0.737). CONCLUSIONS:
      Laparoscopic abdomino-perineal resection is safe and feasible for anastomotic
      recurrence of rectal cancer.

PMID- 24935388
TI  - A potential target of Tanshinone IIA for acute promyelocytic leukemia revealed by
      inverse docking and drug repurposing.
AB  - Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a
      Chinese traditional medicine. Its molecular mechanisms are still unclear. The
      present study utilized computational approaches to uncover the potential targets
      of this compound. In this research, PharmMapper server was used as the inverse
      docking tool and the results were verified by Autodock vina in PyRx 0.8, and by
      DRAR-CPI, a server for drug repositioning via the chemical-protein interactome.
      Results showed that the retinoic acid receptor alpha (RARalpha), a target protein
      in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore
      model matching well the molecular features of Tanshinone IIA. Moreover, molecular
      docking and drug repurposing results showed that the complex was also matched in
      terms of structure and chemical-protein interactions. These results indicated
      that RARalpha may be a potential target of Tanshinone IIA for APL. The study can
      provide useful information for further biological and biochemical research on
      natural compounds.

PMID- 24935389
TI  - Calculation of life-time death probability due malignant tumors based on a
      sampling survey area in China.
AB  - PURPOSE: To calculate the probability of one person's life-time death caused by a
      malignant tumor and provide theoretical basis for cancer prevention. MATERIALS
      AND METHODS: The probability of one person's death caused by a tumor was
      calculated by a probability additive formula and based on an abridged life table.
      All data for age-specific mortality were from the third retrospective
      investigation of death cause in China. RESULTS: The probability of one person's
      death caused by malignant tumor was 18.7% calculated by the probability additive
      formula. On the same way, the life-time death probability caused by lung cancer,
      gastric cancer, liver cancer, esophageal cancer, colorectal and anal cancer were
      4.47%, 3.62%, 3.25%, 2.25%, 1.11%, respectively. CONCLUSIONS: Malignant tumor is
      still the main cause of death in one's life time and the most common causes of
      cancer death were lung, gastric, liver, esophageal, colorectal and anal cancers.
      Targeted forms of cancer prevention and treatment strategies should be worked out
      to improve people's health and prolong life in China. The probability additive
      formula is a more scientific and objective method to calculate the probability of
      one person's life-time death than cumulative death probability .

PMID- 24935390
TI  - Cytotoxic activity of biosynthesized gold nanoparticles with an extract of the
      red seaweed Corallina officinalis on the MCF-7 human breast cancer cell line.
AB  - BACKGROUND: Nano-biotechnology is recognized as offering revolutionary changes in
      the field of cancer therapy and biologically synthesized gold nanoparticles are
      known to have a wide range of medical applications. MATERIALS AND METHODS: Gold
      nanoparticles (GNPs) were biosynthesized with an aqueous extract of the red alga
      Corallina officinalis, used as a reducing and stabilizing agent. GNPs were
      characterized using UV-Vis spectroscopy, transmission electron microscopy (TEM),
      energy dispersive analysis (EDX) and Fourier transform infra-red (FT-IR)
      spectroscopy and tested for cytotoxic activity against human breast cancer (MCF
      7) cells cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal
      bovine serum, considering their cytotoxicty and effects on cellular DNA. RESULTS:
      The biosynthesized GNPs were 14.6 +/- 1 nm in diameter. FT-IR analysis showed
      that the hydroxyl functional group from polyphenols and carbonyl group from
      proteins could assist in formation and stabilization. The GNPs showed potent
      cytotoxic activity against MCF-7 cells, causing necrosis at high concentrations
      while lower concentrations were without effect as indicated by DNA fragmentation
      assay. CONCLUSIONS: The antitumor activity of the biosynthesized GNPs from the
      red alga Corallina officinalis against human breast cancer cells may be due to
      the cytotoxic effects of the gold nanoparticles and the polyphenolcontent of the
      algal extract.

PMID- 24935391
TI  - Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T)
      polymorphisms and esophageal cancer risk in the Kashmir Valley.
AB  - BACKGROUND: Phospholipase C epsilon 1 (PLCE1) encodes a member of the
      phospholipase family of proteins that play crucial roles in carcinogenesis and
      progression of several cancers including esophageal cancer (EC). In two large
      scale genome-wide association studies (GWAS) single nucleotide polymorphisms
      (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel
      susceptibility loci of esophageal cancer (EC) in China. The aim of the present
      study was to investigate this finding in Kashmir Valley, a high risk area.
      MATERIALS AND METHODS: We determined genotypes of three potentially functional
      SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients,
      and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method.
      Risk for developing EC was estimated by binary logistic regression using SPSS.
      RESULTS: The selected PLCE1 polymorphisms did not show independent association
      with EC. However, the G2274223T3765524T7922612 haplotype was significantly
      associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009).
      Smoking and salted tea proved to be independent risk factors for EC. CONCLUSIONS:
      Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri
      population.

PMID- 24935392
TI  - Prevalence of oral pre-malignant lesions and its risk factors in an Indian
      subcontinent low income migrant group in Qatar.
AB  - BACKGROUND: The expatriate population in Qatar largely comprises workers from the
      Indian subcontinent which has a very high rate of oral malignancy. Social and
      cultural habits and as well premalignant risk factors in this population remain
      prevalent even after migration. MATERIALS AND METHODS: This cross sectional study
      assessed the prevalence of risk factors and occurrence of oral precancerous
      lesions in a low income group expatriate community from the Indian subcontinent
      residing in Qatar. RESULTS: Among the 3,946 participants screened for oral
      premalignant lesions 24.3% (958) were smokers and 4.3 % (169) were pan chewers
      while 6.3% (248) were users of both smoked and smokeless forms of tobacco.
      Significantly higher proportion of industrial laborers (49.9%) followed by
      drivers (24.1%) were found to be smokers (p=0.001). The prevalence of white
      lesions was higher in smokers versus non-smokers 3.5% versus 2.3% (p=0.111),
      however this difference was statistically non-significant. Red and white lesions
      were highly significant (i.e. 1.2 % and 10.9% respectively) in the subjects with
      pan chewing and smoking habits (p=0.001). A significant proportion (8.9%) of the
      subjects with pan chewing habit showed evidence of oral precancerous lesions
      (p=0.001). CONCLUSIONS: Even though smoking and pan chewing were two significant
      risk factors detected in this population, their prevalence and occurrence of
      premalignant lesions are low as compared to the studies conducted in their home
      countries.

PMID- 24935393
TI  - A novel suberoylanilide hydroxamic acid histone deacetylase inhibitor derivative,
      N25, exhibiting improved antitumor activity in both human U251 and H460 cells.
AB  - N1- (2, 5-dimethoxyphenyl)-N(8)-hydroxyoctanediamide (N25) is a novel SAHA cap
      derivative of HDACi, with a patent (No. CN 103159646). This invention is a
      hydroxamic acid compound with a structural formula of RNHCO(CH2)6CONHOH (wherein
      R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In
      the present study, we investigated the effects of N25 with regard to drug
      distribution and molecular docking, and anti-proliferation, apoptosis, cell
      cycling, and LD50. First, we designed a molecular approach for modeling selected
      SAHA derivatives based on available structural information regarding human HDAC8
      in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct
      interaction with the HDAC8. Anti-proliferative activity was observed in human
      glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at
      moderate concentrations (0.5-30 MUM). Compared with SAHA, N25 displayed an
      increased antitumor activity in U251 and H460 cells. We further analyzed cell
      death mechanisms activated by N25 in U251 and H460 cells. N25 significantly
      increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25
      increased the mRNA levels of p21, however, decreased the levels of p53. These
      resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M
      arrest in H460 cells in a time-dependent and dose- dependent manner. In addition,
      N25 was able to distribute to brain tissue through the blood-brain barrier of
      mice (LD50: 240.840 mg/kg). In conclusion, our findings demonstrate that N25 will
      provide an invaluable tool to investigate the molecular mechanism with potential
      chemotherapeutic value in several malignancies, especially human glioma.

PMID- 24935394
TI  - Total delay for treatment among cancer patients: a theory-guided survey in China.
AB  - PURPOSE: This study aimed at exploring treatment delay (TD) among cancer patients
      in China with an attempt to develop a practical methodology facilitating
      frontline Chinese clinicians in promoting earlier cancer diagnosis and treatment.
      MATERIALS AND METHODS: The study comprised framework development, qualitative
      interviews and paired factor rating. Framework development utilized systematic
      literature review, soft systems thinking and consensus groups. Qualitative
      interviews employed a checklist of open questions soliciting information about
      all the domains included the framework from cancer patients drawn via stratified
      randomized sampling of inpatients at 10 hospitals in Hefei, China. Paired factor
      rating used a self-developed computer aid and the interviewed patients as
      referring cases to weigh the relative importance of the factors listed in the
      framework in terms of their contributions to specific components of total delay
      (TD). RESULTS: a) A conceptual framework was proposed consisting of a 6-step path
      to TD and 36 category determinants. b) A total of 227 patients were interviewed;
      their TD was 267.3 mean or 108 median days ranging from 0 to 2475 days; average
      appraisal, illness, behavioral, preparation and treatment delay accounted for
      52.1%, 9.4%, 0.30%, 8.8% and 29.4% of the TD respectively. Individual side
      factors were rated substantially more important than environmental side factors
      (60% vs. 40%); most influential TD factors included cancer symptoms, overall
      health, family relations and knowledge about cancer and health. CONCLUSIONS: The
      framework proposed together with the interviewing and rating approaches used
      provide a potential new methodology for understanding cancer patients' TD and
      promoting earlier cancer treatment.

PMID- 24935395
TI  - Clinical, laboratory biomarkers and imaging findings of pancreatic adenocarcinoma
      in Iran.
AB  - BACKGROUND: Pancreatic cancer has a high mortality rate because it is usually
      diagnosed late. Since little is known about this cancer in Iran, with the aim of
      improving this knowledge deficiency, we evaluated clinical, laboratory
      biomarkers, imaging findings and treatment modalities in Iranian patients with
      pancreatic adenocarcinoma. MATERIALS AND METHODS: 131 cases of pancreatic
      adenocarcinoma in 2010-2013 were obtained from the Taleghani Hospital Record
      Department. Cases confirmed by histopathology from CT-guided biopsy, EUS-FNA and
      surgery examination were included. We excluded those with incomplete medical
      records. RESULTS: The study included 131 subjects between 24 and 97 years of age
      and a mean age of 63 +/- 13.4 years. Eighty (61.1%) were male and 51 (38.9%)
      female. Previous history included diabetes mellitus in 36 (27.5%), alcohol
      drinking in 5 (3.9%), smoker in 28 (21.4%) and opium addiction in 13 (10%) . The
      common presenting history included weight loss in 79 (60.3%), abdominal pain in
      77 (58.8%), fever in 11 (8.4%), nausea in 30 (22.9%), jaundice in 72 (55%),
      pruritus in 52 (39.7) and anemia in 33 (25.2%) . CA19-9 levels with cut offs of
      50, 100 and 200 U/ml were increased in 81%, 72% and 66% of patients,
      respectively. Tumor staging was: stage I, 3 (2.3%); stage II, 10 (7.6%); stage
      III, 58 (44.3%); and stage IV, 60 (45.8%). From 45 patients, 17 received ERCP
      inserted metallic stents and 22 plastic stents, the remaining 6 failed that PTC
      was done. Whipple surgery and chemotherapy were conducted for 10 and 29 patients,
      respectively. CONCLUSIONS: This disease affected older people and there was a
      male preponderance. The commonest risk factors were diabetes mellitus, smoking
      and cholelithiasis. The majority of patients presented with loss of appetite,
      loss of weight, jaundice, abdominal pain and discomfort. Almost all presented at
      late stages of the disease so that curative surgery was impossible. Also
      chemotherapy was only performed in a few patients as a neoadjuant treatment.

PMID- 24935396
TI  - Molecular target therapy of AKT and NF-kB signaling pathways and multidrug
      resistance by specific cell penetrating inhibitor peptides in HL-60 cells.
AB  - BACKGROUND: PI3/AKT and NF-kB signaling pathways are constitutively active in
      acute myeloid leukemia and cross-talk between the two has been shown in various
      cancers. However, their role in acute myeloid leukemia has not been completely
      explored. We therefore used cell penetrating inhibitor peptides to define the
      contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL
      60 cells. MATERIALS AND METHODS: Inhibition of AKT and NF-kB activity by AKT
      inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased
      expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition,
      treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of
      cell viability and induction of apoptosis in a dose dependent manner as detected
      by flow cytometer. RESULTS: Finally, co-treatment of HL-60 cells with sub-optimal
      doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in
      AML cells. CONCLUSIONS: These data support a strong biological link between NF-kB
      and PI3-kinase/AKT pathways in the modulation of anti- apoptotic and multi drug
      resistant effects in AML cells. Synergistic targeting of these pathways using NF
      kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML
      and possibly other malignancies with constitutive activation of these pathways.

PMID- 24935397
TI  - Prevalence and factors associated with smoking intentions among non-smoking and
      smoking adolescents in Kota Tinggi, Johor, Malaysia.
AB  - Intention to smoke is a valid and reliable factor for predicting future smoking
      habits among adolescents. This factor, however, has received inadequate attention
      in Malaysia. The present paper elaborates the prevalence and factors associated
      with intent to initiate or to cease smoking, among adolescent nonsmokers and
      smokers in Kota Tinggi, Johor, Malaysia. A total of 2,300 secondary school
      students aged 13-16 years were selected through a two-stage stratified sampling
      method. A set of standardized questionnaires was used to assess the smoking
      behavior among adolescents and the inter-personal and intra-personal factors
      associated with smoking intention (intention to initiate smoking or to cease
      smoking). Multivariable logistic regression was used to identify factors related
      to smoking intention. The prevalence of intention to smoke in the future or to
      cease smoking among non- smoking adolescents and current smokers were 10.7% and
      61.7% respectively. Having friends who smoke, social influence, and poor
      knowledge about the ill effects on health due to smoking showed significant
      relationships with intention to smoke in the future among non-smokers.
      Conversely, perceived lower prevalence of smoking among peers, weak contributory
      social influence, and greater awareness of the ill effects of smoking are factors
      associated with the intention to cease smoking sometime in the future. The study
      found that prevalence of intention to initiate smoking is low among non-smokers
      while the majority of current smokers intended to cease smoking in the future.
      Existing anti-smoking programmes that integrate the factors that have been
      identified in the current study should be put in motion to reduce the prevalence
      of intention to initiate smoking and increase the intention to cease smoking
      among adolescents.

PMID- 24935398
TI  - Expression and clinical significance of myeloid derived suppressor cells in
      chronic hepatitis B patients.
AB  - We here document discovery of expression profile of myeloid derived suppressor
      cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of
      disease. The study population was composed of 75 outpatient HBV cases and 15
      healthy control cases. Peripheral blood samples were collected for separation of
      mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from
      peripheral blood mononuclear cells (PBMC), were revealed to have significant
      differences between the CHB and other groups. They were 0.414% for health control
      cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the
      group of HBeAg positive cases had significant difference in MDSCs/ PBMC median
      (X(2)=11.877, p=0.003), compared with group of HBeAg negative cases and the
      healthy control group. It suggested considerable MDSCs might be involved in HBeAg
      immune tolerance. In addition, negative correlations between MDSCs/PBMC and
      parameters of ALT, AST and TBil, while positive correlation between MDSCs/ PBMC
      and ALB parameter were found. Multiple comparisons between the four phases and
      health control phase again, there was a statistically sifnificant difference
      (X(2)=17.198, p=0.002). Taken together, these findings may provide a new
      immunotherapy strategy for reduced the expression levels of MDSCs in CHB
      patients, through induction of an autoimmune response to virus removal.

PMID- 24935399
TI  - Is the combination of neutrophil to lymphocyte and platelet to lymphocyte ratios
      a useful predictor of treatment response and prognosis in patients with non-small
      cell lung cancer?

PMID- 24935400
TI  - The potential role of human papillomavirus in colorectal carcinoma.

PMID- 24935401
TI  - Retapamulin prescriptions and monitored off-label use.
AB  - INTRODUCTION: Retapamulin, a topical pleuromutilin that selectively inhibits
      bacterial protein synthesis, is approved for treatment of impetigo and
      secondarily infected traumatic lesions in adults and in children older than 9
      months of age. OBJECTIVE: A 5-year study was conducted to monitor prescription
      use in children younger than 9 months of age. METHODS: Annual prescription events
      were monitored in the UK Clinical Practice Research Datalink (CPRD) and the
      ClinformaticsTM DataMart Multiplan (IMPACT), a product of OptumInsight Life
      Sciences, Inc. (Eden Prairie, MN, USA), from the USA. RESULTS: In the CPRD, of
      148 prescriptions, three (2 %) were identified in children aged less than 9
      months between years 2008 and 2011. In IMPACT, of 59,210 claims for retapamulin
      in children, 1,951 (3.3 %) were categorized as definitive, or uncertain for, less
      than 9 months of age between 2007 and 2011. CONCLUSION: Retapamulin prescription
      events in children aged less than 9 months were relatively low compared with
      other recent estimations of off-label pediatric medicines. Our report provides a
      framework for future investigations and discussions that may facilitate off-label
      reporting schemes and promote pediatric drug safety.

PMID- 24935403
TI  - Quantitative proteomic analysis of whey proteins in the colostrum and mature milk
      of yak (Bos grunniens).
AB  - BACKGROUND: Yak (Bos grunniens) is an important natural resource in mountainous
      regions. To date, few studies have addressed the differences in the protein
      profiles of yak colostrum and milk. We used quantitative proteomics to compare
      the protein profiles of whey from yak colostrum and milk. Milk samples were
      collected from 21 yaks after calving (1 and 28 d). Whey protein profiles were
      generated through isobaric tag for relative and absolute quantification (iTRAQ)
      labelled proteomics. RESULTS: We identified 183 proteins in milk whey; of these,
      the expression levels of 86 proteins differed significantly between the whey from
      colostrum and milk. Haemoglobin expression showed the greatest change; its levels
      were significantly higher in the whey from colostrum than in mature milk whey.
      Functional analysis revealed that many of the differentially expressed proteins
      were associated with biological regulation and response to stimuli. Further,
      eight differentially expressed proteins involved in the complement and
      coagulation cascade pathway were enriched in milk whey. CONCLUSION: These
      findings add to the general understanding of the protein composition of yak milk,
      suggest potential functions of the differentially expressed proteins, and provide
      novel information on the role of colostral components in calf survival.

PMID- 24935402
TI  - Statin use and its effect on all-cause mortality of melanoma patients: a
      population-based Dutch cohort study.
AB  - Preclinical data showed anticancer effects of statins in melanoma, but meta
      analyses could not demonstrate a reduced melanoma incidence in statin users.
      Rather than preventing occurrence, statins might reduce growth and metastatic
      spread of melanomas and ultimately improve survival. In this population-based
      study, we investigated the relationship between statin use and survival of
      melanoma patients. Patients >=18 years who were diagnosed with cutaneous melanoma
      (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in
      PHARMO Database Network between 1 January 1998 and 31 December 2010 were
      eligible. The hazard ratio (HR) of all-cause mortality was calculated by
      employing adjusted time-dependent and time-fixed Cox proportional hazard models.
      Disease-specific survival was estimated by means of 3-year relative survival
      rates (RSR). A control cohort of randomly selected patients using statins from
      PHARMO Database Network matched on age and gender was used to compare RSR of
      statin users to the general population. After melanoma diagnosis, 171 of 709
      patients used statins. Use of statins showed a nonsignificantly decreased hazard
      of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50-1.61). After
      stratification for gender, male but not female statin users showed a favorable
      outcome compared to nonusers (HR 0.57, 95% CI 0.32-0.99; HR 1.22, 95% CI 0.62
      2.38, respectively). Three-year RSR for male statin users tended to be higher
      than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in
      women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved
      survival of melanoma patients. The trend for better survival of male in contrast
      to female statin users warrants further research. 

PMID- 24935404
TI  - Effect of dietary inclusion of Leucaena leucocephala or Moringa oleifera leaf
      meal on performance of growing rabbits.
AB  - This experiment was carried out to evaluate the effect of including either
      Leucaena leucocephala (LLM) or Moringa oleifera leaf meal (MOLM) as tropical feed
      resources at two levels (30 or 40 %) on growth performance, carcass traits, and
      economical efficiency of growing rabbits. A total of 60 California growing
      rabbits were randomly distributed into five experimental groups, each consisting
      of 12 rabbits and were allocated individually; the groups were control, 30 % LLM,
      40 % LLM, 30 % MOLM, and 40 % MOLM. The experimental period lasted from 6 to 12
      weeks of age. The results showed that rabbits fed control and 30 % MOLM diets had
      significantly the highest final body weight and daily weight gain being 2,040 and
      2,000 g and 31.6 and 30.6 g/day, respectively. Similarly, the best feed
      conversion ratio was associated with 30 % MOLM and control groups (3.2 and 3.4),
      while the worst value was for 40 % LLM group (5.2). MOLM treatments recorded
      significantly the highest dressing percentage along with control group. The
      inclusion of MOLM by 30 and 40 % improved the economical efficiency (2 and 1.5)
      in comparison with the control group (1.1). The results suggest that MOLM can be
      included in growing rabbit diets up to 40 % without any adverse effect on growth
      performance or carcass traits with higher economical efficiency of growing
      rabbits.

PMID- 24935405
TI  - Electrodynamics of soft multilayered particles dispersions: dielectric
      permittivity and dynamic mobility.
AB  - We report a theory for the evaluation of the electrodynamics of dispersions of
      spherical soft multilayered (bio)particles, with microorganisms and
      polyelectrolyte multilayers-coated particles as illustrative paradigms. These
      particles generally consist of a hard (ion- and water-impermeable) core component
      supporting a succession of step-function or diffuse-like concentric soft
      (permeable) polymeric layers defined by distinct electrostatic, hydrodynamic and
      structural properties. The formalism is based on a rigorous numerical resolution
      of the coupled Navier-Stokes-Brinkman equation, continuity equations for the flow
      and for the ionic species present in solution, and the non-linear Poisson
      equation corrected for the multilayered nature of the soft interphase. The
      frequency-dependent dynamic mobility and dielectric permittivity of such soft
      particles suspensions are discussed as a function of the key electrohydrodynamic
      features of the constituting particulate peripheral layers and solution salinity.
      It is shown that the frequency dependent permittivity is mostly affected by the
      total charge carried by the overall soft interphase. In contrast, the dynamic
      mobility is mainly determined by the charge and friction characteristics of the
      layers located within an electrokinetically-active outer particle region whose
      extension is defined by the electric double layer thickness and the Brinkman
      length. Results highlight that under particular electrolyte concentration and
      layer-to-layer thickness ratio conditions, the dynamic mobility may reflect the
      physico-chemical and structural properties of the only innermost layers of the
      soft particle coating. 

PMID- 24935407
TI  - Inclusion of intersite spatial correlations in the alloy analogy approach to the
      half-filled ionic Hubbard model.
AB  - Using the nonlocal coherent-potential approximation we study the effect of
      intersite spatial correlations on the transition from band insulator to metal as
      well as from metal to Mott insulator in the 'alloy analogy' approach to the
      paramagnetic solution of the half-filled ionic Hubbard model. We find that
      intersite spatial correlations enhance the metallic phase. 

PMID- 24935406
TI  - Effects of schizophrenia risk variation in the NRG1 gene on NRG1-IV splicing
      during fetal and early postnatal human neocortical development.
AB  - OBJECTIVE: Neuregulin 1 (NRG1) is a multifunctional neurotrophin that mediates
      neurodevelopment and schizophrenia risk. The NRG1 gene undergoes extensive
      alternative splicing, and association of brain NRG1 type IV isoform expression
      with the schizophrenia-risk polymorphism rs6994992 is a potential mechanism of
      risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique
      signaling capabilities, have been cloned in fetal brain tissue. The authors
      investigated the temporal dynamics of transcription of NRG1-IVNV, compared with
      the major NRG1 isoforms, across human prenatal and postnatal prefrontal cortical
      development, and they examined the association of rs6994992 with NRG1-IVNV
      expression. METHOD: NRG1 type I-IV and NRG1-IVNV isoforms were evaluated with
      quantitative real-time polymerase chain reaction in human postmortem prefrontal
      cortex tissue samples at 14 to 39 weeks gestation and postnatal ages 0-83 years.
      The association of rs6994992 genotype with NRG1-IVNV expression and the
      subcellular distribution and proteolytic processing of NRG1-IVNV isoforms were
      also determined. RESULTS: Expression of NRG1 types I, II, and III was temporally
      regulated during prenatal and postnatal neocortical development. NRG1-IVNV was
      expressed from 16 weeks gestation until age 3. Homozygosity for the schizophrenia
      risk allele (T) of rs6994992 conferred lower cortical NRG1-IVNV levels. Assays
      showed that NRG1-IVNV is a novel nuclear-enriched, truncated NRG1 protein
      resistant to proteolytic processing. CONCLUSIONS: To the authors' knowledge, this
      study provides the first quantitative map of NRG1 isoform expression during human
      neocortical development and aging. It identifies a potential mechanism of early
      developmental risk for schizophrenia at the NRG1 locus, involving a novel class
      of NRG1 proteins.

PMID- 24935408
TI  - Immunoregulation effects of bone marrow-derived mesenchymal stem cells in
      xenogeneic acellular nerve grafts transplant.
AB  - This study evaluated whether bone marrow-derived mesenchymal stem cells (BM-MSCs)
      combined with xenogeneic acellular nerve grafts (xANGs) would reduce the
      inflammation reaction of xANGs transplantation. BM-MSCs were extracted,
      separated, purified, and cultured from the bone marrow of rats. Then BM-MSCs were
      seeded into 5 mm xANGs as experimental group, while xANGs group was chosen as
      control. Subcutaneous implantation and nerve grafts transplantation were done in
      this study. Walking-track tests, electrophysiological tests, H&E staining, and
      immunostaining of CD4, CD8, and CD68 of subcutaneous implantations, cytokine
      concentrations of IL-2, IL-10, IFN-gamma and TNF-alpha in lymphocytes
      supernatants and serum of the two groups were evaluated. Walking-track tests and
      electrophysiological tests suggested the group of BM-MSCs with xANGs obtained
      better results than xANGs group (P < 0.05). H&E staining and immunostaining of
      CD4, CD8, and CD68 of subcutaneous implantations showed there were less
      inflammatory cells in the group of BM-MSCs when compared with the xANGs group.
      The cytokine concentrations of IL-2, IFN-gamma, and TNF-alpha in BM-MSCs group
      were lower than xANGs group in lymphocytes supernatants and serum (P < 0.05).
      However, IL-10 concentrations in BM-MSCs group were higher than xANGs group (P <
      0.05). xANG with BM-MSCs showed better nerve repair function when compared with
      xANG group. Furthermore, xANG with BM-MSCs showed less inflammatory reaction
      which might indicate the reason of its better nerve regeneration.

PMID- 24935410
TI  - Waiting for words.

PMID- 24935409
TI  - Inhibition of MMP-2 but not MMP-9 influences inner ear spiral ganglion neurons in
      vitro.
AB  - Matrix metalloproteinases (MMPs) play an important role in modeling of the
      extracellular matrix. There is increasing evidence that these proteases are
      important in neurite elongation and axonal guidance during development in the
      central nervous system and retina. Moreover, they are also expressed after acute
      injury and can be the key mediators of pathogenesis. However, the role of MMPs in
      the inner ear is largely unknown. Our group recently demonstrated that general
      inhibition of MMPs resulted in auditory hair cell loss in vitro. In the present
      study, we investigated the role of MMPs in inner ear spiral ganglion neuron (SGN)
      survival, neuritogenesis and neurite extension by blocking MMPs known to be
      involved in axonal guidance, neurite elongation, and apoptosis in other neuronal
      systems. Spiral ganglion (SG) explants from 5-day-old Wistar rats were treated
      with different concentrations of the general MMP inhibitor GM6001, a specific MMP
      2 inhibitor, and a specific MMP-9 inhibitor, in vitro. The general inhibitor of
      MMPs and the specific inhibition of MMP-2 significantly reduced both the number
      of neurites that extended from SG explants, as well as the length of individual
      neurites. However, neither the general inhibitor of MMPs nor the specific
      inhibition of MMP-2 influenced SGN survival. Inhibition of MMP-9 had no influence
      on SGNs. The data suggest that MMPs, and more specifically MMP-2, influence the
      growth of developing afferent neurites in the mammalian inner ear in vivo.

PMID- 24935412
TI  - Methods of assessment of tophus and bone erosions in gout using dual-energy CT:
      reproducibility analysis.
AB  - This study aims to evaluate the intraobserver and interobserver reproducibility
      of the tophus urate volume, erosion volume, and the erosion score measurements in
      patients with gout by using dual-energy CT (DECT) scans comparing their bone
      erosion volumes against bone erosion scores and also to determine a valid measure
      of joint destruction in chronic gout. Sixty-six subjects underwent DECT scans of
      the hands or feet. Two independent observers measured the tophus urate volumes
      and bone erosion volumes using automated volume assessment software and the
      erosion scores based on the rheumatoid arthritis magnetic resonance imaging score
      (RAMRIS). The intraobserver and interobserver reproducibility were analyzed by
      intraclass correlation coefficient (ICC) and limits of agreements analysis. The
      relationship between erosion volumes and erosion scores was analyzed. The
      intraobserver and interobserver ICC for tophus urate volume measurements (n =
      636) were 1.000 (95 % confidence interval (95 % CI) 1.000 to 1.000) and 1.000 (95
      % CI 1.000 to 1.000), 0.999 (0.999, 0.999) and 0.999 (0.999, 0.999) for bone
      erosion volumes (n = 350), 0.937 (0.928, 0.946) and 0.899 (0.883, 0.912) for
      erosion scores (n = 350). Strong positive correlations were demonstrated between
      individual erosion volumes and scores (r s = 0.914, p < 0.001) as well as total
      erosion volume and score per patient (r = 0.838-0.867, p < 0.001). This study
      demonstrated a high reproducibility of tophus urate volumes, erosion volumes, and
      erosion score measurements using DECT. Erosion volumes show to be a more direct
      and accurate method to evaluate bone erosion compared with erosion score,
      strongly supporting it as a superior and standard measure of structural joint
      damage in gout.

PMID- 24935413
TI  - Posterior cerebral artery stroke presenting as alexia without agraphia.
AB  - Alexia without agraphia (pure alexia) was the first of the disconnection
      syndromes to be described by Dejerine who reported a patient of alexia without
      agraphia secondary to an embolic occipital lobe infarct. We herein report a 55
      year-old man who presented with alexia without agraphia with magnetic resonance
      imaging suggestive of left posterior cerebral artery infarct involving left
      occipital lobe and splenium of corpus callosum. Alexia without agraphia is a
      relatively uncommon clinical condition, which should always be thought in a
      patient presenting with difficulty in reading with normal visual acuity.
      Ophthalmologists should also be aware of this disconnection syndrome as many
      patients initially take their advice due to predominant visual complaints. Early
      diagnosis and treatment of this condition help in ensuring the patient and
      attendants about nonprogressive nature of the disease and may prevent further
      episodes of stroke.

PMID- 24935411
TI  - Key facts and hot spots on tumor necrosis factor receptor-associated periodic
      syndrome.
AB  - Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), formerly
      known as familial Hibernian fever, is the most common autosomal dominant
      autoinflammatory disease, resulting from mutations in the TNFRSF1A gene, encoding
      the 55-kD tumor necrosis factor receptor. The pathophysiologic mechanism of TRAPS
      remains ambiguous and only partially explained. The onset age of the syndrome is
      variable and the clinical scenery is characterized by recurrent episodes of high
      grade fever that typically lasts 1-3 weeks, associated with migrating myalgia,
      pseudocellulitis, diffuse abdominal pain, appendicitis-like findings, ocular
      inflammatory signs, and risk of long-term amyloidosis. Fever episodes are
      responsive to high-dose corticosteroids, but different classes of drugs have been
      reported to be ineffective. The use of etanercept is unable to control systemic
      inflammation, while interleukin-1 blockade has been shown as effective in the
      control of disease activity in many patients reported so far.

PMID- 24935414
TI  - Evaluation of the cloudy sky solar UVA radiation exposures.
AB  - The influence of cloud on the solar UVA (320-400 nm) exposures over five minute
      periods on a horizontal plane has been investigated. The first approach used
      cloud modification factors that were evaluated using the influence of clouds on
      the global solar exposures (310-2800 nm) and a model developed to apply these to
      the clear sky UVA exposures to allow calculation of the five minute UVA exposures
      for any cloud conditions. The second approach established a relationship between
      the UVA and the global solar exposures. The models were developed using the first
      six months of data in 2012 for SZA less than or equal to 70 degrees  and were
      applied and evaluated for the exposures in the second half of 2012. This
      comparison of the modelled exposures for all cloud conditions to the measured
      data provided an R(2) of 0.8 for the cloud modification model, compared to an
      R(2) of 0.7 for the UVA/global model. The cloud modification model provided 73%
      of the five minute exposures within 20% of the measured UVA exposures. This was
      improved to 89% of the exposures within 20% of the measured UVA exposures for the
      cases of cloud with the sun not obscured.

PMID- 24935415
TI  - Raman ratios on the repair of grafted surgical bone defects irradiated or not
      with laser (lambda780 nm) or LED (lambda850 nm).
AB  - This work aimed to assess biochemical changes associated to mineralization and
      remodeling of bone defects filled with Hydroxyapatite+Beta-Beta-tricalcium
      phosphate irradiated or not with 2 light sources. Ratios of intensities, band
      position and bandwidth of selected Raman peaks of collagen and apatites were
      used. Sixty male Wistar rats were divided into 6 groups subdivided into 2
      subgroups (15th and 30th days). A standard surgical defect was created on one
      femur of each animal. In 3 groups the defects were filled with blood clot (Clot,
      Clot+Laser and Clot+LED groups) and in the remaining 3 groups the defects were
      filled with biomaterial (Biomaterial, Biomaterial+Laser and Biomaterial+LED
      groups). When indicated, the defects were irradiated with either Laser (lambda780
      nm, 70 mW, Phi~0.4 cm(2)) or LED (lambda850+/-10 nm, 150 mW, Phi~0.5 cm(2)), 20
      J/cm(2) each session, at 48 h intervals/2 weeks (140 J/cm(2) treatment).
      Following sacrifice, bone fragments were analyzed by Raman spectroscopy.
      Statistical analysis (ANOVA General Linear Model, p<0.05) showed that both
      grafting and time were the variables that presented significance for the ratios
      of ~1660/~1670 cm(-1) (collagen maturation), ~1077/~854 cm(-1) (mineralization),
      ~1077/~1070 cm(-1) (carbonate substitution) and the position of the ~960 cm(-1)
      (bone maturation). At 30th day, the ratios indicated an increased deposition of
      immature collagen for both Clot and Biomaterial groups. Biomaterial group showed
      increased collagen maturation. Only collagen deposition was significantly
      dependent upon irradiation independently of the light source, being the amount of
      collagen I increased in the Clot group at the end of the experimental time. On
      the other hand, collagen I deposition was reduced in biomaterial irradiated
      groups. Raman ratios of selected protein matrix and phosphate and carbonate HA
      indicated that the use of biphasic synthetic micro-granular HA+Beta-TCP graft
      improved the repair of bone defects, associated or not with Laser or LED light,
      because of the increasing deposition of HA.

PMID- 24935416
TI  - Effect of humic acid on photocatalytic activity of ZnO nanoparticles.
AB  - Zinc oxide nanoparticles (ZnO NPs) are widely used in consumer products including
      sunscreens, textiles and paints. The indiscriminate use of such materials may
      leads to its release into the environment. The present study evaluated the
      photocatalytic effect of ZnO NPs in presence of humic acid (HA), which is an
      important factor present largely in the environment. ZnO NPs were characterized
      by using UV-visible spectrophotometer, scanning electron microscopy, particle
      size analyzer and X-ray diffraction analysis. The mean diameter of the particles
      was found to be 55+/-2.1 nm. The XRD patterns exhibited hexagonal structure for
      ZnO NPs. The photocatalytic activity of ZnO NPs was evaluated based on the change
      in UV-visible absorption spectra of the methylene blue solution as a function of
      reaction time under visible light source. The rate of photocatalytic degradation
      of methylene blue was decreased with increase in HA concentration.

PMID- 24935417
TI  - Upper gastrointestinal bleeding: risk scores and clinical judgment in predicting
      outcomes of UGIB.
AB  - Predicting outcomes in upper gastrointestinal bleeding (UGIB) is important for
      identifying patients at high risk of morbidity and mortality who would benefit
      from early intervention. Various scoring systems have been developed to this end,
      but could clinical judgment replace or complement these risk stratification
      scores?

PMID- 24935418
TI  - Gut microbiota: stunted gut microbiota development persists after therapeutic
      food interventions in children with severe acute malnutrition.

PMID- 24935420
TI  - Liver: the liver as a firewall--clearance of commensal bacteria that have escaped
      from the gut.

PMID- 24935421
TI  - Biliary tract. IL-33, innate lymphoid cells and IL-13 are required for
      cholangiocyte proliferation.

PMID- 24935422
TI  - Coeliac disease: noncoeliac gluten sensitivity--food for thought.
AB  - Patients with noncoeliac gluten sensitivity (NCGS) can experience a range of
      gastrointestinal and extraintestinal symptoms. A study has now demonstrated that
      gluten is independently associated with depression in patients with NCGS. NCGS
      associated depression might share similar pathophysiological mechanisms to other
      neurological manifestations observed in gluten-related disorders, such as ataxia
      and encephalopathy.

PMID- 24935426
TI  - Intracellular remodelling of Ca2+ stores in pulmonary hypertension.

PMID- 24935428
TI  - HDL in innate and adaptive immunity.
AB  - During infections or acute conditions high-density lipoproteins cholesterol (HDL
      C) levels decrease very rapidly and HDL particles undergo profound changes in
      their composition and function. These changes are associated with poor prognosis
      following endotoxemia or sepsis and data from genetically modified animal models
      support a protective role for HDL. The same is true for some parasitic
      infections, where the key player appears to be a specific and minor component of
      HDL, namely apoL-1. The ability of HDL to influence cholesterol availability in
      lipid rafts in immune cells results in the modulation of toll-like receptors, MHC
      II complex, as well as B- and T-cell receptors, while specific molecules shuttled
      by HDL such as sphingosine-1-phosphate (S1P) contribute to immune cells
      trafficking. Animal models with defects associated with HDL metabolism and/or
      influencing cell cholesterol efflux present features related to immune disorders.
      All these functions point to HDL as a platform integrating innate and adaptive
      immunity. The aim of this review is to provide an overview of the connection
      between HDL and immunity in atherosclerosis and beyond. 

PMID- 24935429
TI  - The energetic cost of contraction is higher in the myocardium of patients with
      hypertrophic cardiomyopathy.

PMID- 24935427
TI  - Critical role of matrix metalloprotease-9 in chronic high fat diet-induced
      cerebral vascular remodelling and increase of ischaemic brain injury in mice?.
AB  - AIMS: About one-third of American adults and 20% of teenagers are obese. Obesity
      and its associated metabolic disturbances including hyperlipidaemia are risk
      factors for cardiovascular diseases including stroke. They can worsen
      neurological outcome after stroke. We determined whether obesity and
      hyperlipidaemia could induce cerebral vascular remodelling via matrix
      metalloproteases (MMP) and whether this remodelling affected neurological outcome
      after brain ischaemia. METHODS AND RESULTS: Six-week-old male CD1, C57BL/6J, and
      MMP-9(-/-) mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks.
      They were subjected to vascular casting or a 90 min middle cerebral arterial
      occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid
      levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral
      vascular tortuosity index and decreased inner diameters of the middle cerebral
      arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex.
      After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe
      brain oedema and blood-brain barrier damage, higher haemorrhagic transformation
      rate, greater haemorrhagic volume, and worse neurological function. HFD increased
      MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD
      increased the body weights, blood glucose, and lipid levels in the MMP-9(-/-)
      mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular
      remodelling and worsening of neurological outcome did not occur in these mice.
      CONCLUSION: HFD induces cerebral vascular remodelling and worsens neurological
      outcome after transient focal brain ischaemia. MMP-9 activation plays a critical
      role in these HFD effects.

PMID- 24935430
TI  - Mechanisms underlying capsaicin effects in canine coronary artery: implications
      for coronary spasm.
AB  - AIMS: The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin
      is considered to be beneficial for cardiovascular health because it dilates
      coronary arteries through an endothelial-dependent mechanism and may slow
      atheroma progression. However, recent reports indicate that high doses of
      capsaicin may constrict coronary arterioles and even provoke myocardial
      infarction. Thus far, the mechanisms by which TRPV1 activation modulates coronary
      vascular tone remain poorly understood. This investigation examined whether there
      is a synergistic interplay between locally acting vasoconstrictive pro
      inflammatory hormones (autacoids) and capsaicin effects in the coronary
      circulation. METHODS AND RESULTS: Experiments were performed in canine conduit
      coronary artery rings and isolated smooth muscle cells (CASMCs). Isometric
      tension measurements revealed that 1-10 MUM capsaicin alone did not affect
      resting tension of coronary artery rings. In contrast, in endothelium-intact
      rings pre-contracted with a Gq/11-coupled FP/TP (prostaglandin F/thromboxane)
      receptor agonist, prostaglandin F2alpha (PGF2alpha; 10 MUM), capsaicin first
      induced transient dilation that was followed by sustained contraction. In
      endothelium-denuded rings pre-contracted with PGF2alpha or thromboxane analogue
      U46619 (1 MUM, a TP receptor agonist), capsaicin induced only sustained
      contraction. Blockers of the TP receptor or TRPV1 significantly inhibited
      capsaicin effects, but these were still observed in the presence of 50 MUM
      nifedipine and 70 mM KCl. Capsaicin also potentiated 20 mM KCl-induced
      contractions. Fluorescence imaging experiments in CASMCs revealed that the Gq/11
      phospholipase C (PLC)-protein kinase C (PKC) and Ca(2+)-PLC-PKC pathways are
      likely involved in sensitizing CASMC TRPV1 channels. CONCLUSION: Capsaicin alone
      does not cause contractions in conduit canine coronary artery; however, pre
      treatment with pro-inflammatory prostaglandin-thromboxane agonists may unmask
      capsaicin's vasoconstrictive potential.

PMID- 24935432
TI  - High-density lipoproteins as modulators of endothelial cell functions:
      alterations in patients with coronary artery disease.
AB  - Alteration of endothelial cell functions, including reduced endothelial nitric
      oxide (NO) availability, increased endothelial cell apoptosis, adhesion
      molecule/chemokine expression and pro-thrombotic activation are thought to
      contribute to the pathophysiology of atherosclerosis and coronary-artery-disease
      (CAD) with its clinical complications, such as acute coronary syndromes. High
      density lipoproteins (HDL) from healthy subjects or reconstituted HDL have been
      observed to exert potential direct anti-atherogenic effects by modulating these
      endothelial cell functions. Importantly, endothelial effects of HDL have now been
      reported to be highly heterogeneous, and are modulated as part of immune
      responses. More recently, this has also been observed for HDL of patients with
      CAD, where HDL becomes potentially pro-inflammatory and endothelial-protective
      properties are markedly altered. Several mechanisms may lead to these altered
      endothelial effects of HDL in patients with CAD, including oxidative modification
      of HDL-associated lipids and proteins, such as apoA-I and paraoxonase-1, and
      alterations of HDL-proteome. These findings have to be considered with respect to
      interpretation of recent clinical studies failing to demonstrate reduced
      cardiovascular events by HDL-cholesterol raising strategies in patients with CAD.
      Both clinical and genetic studies suggest that HDL-cholesterol levels alone are
      not a sufficient therapeutic target in patients with CAD. The focus of this
      review is to summarize the role of HDL onto endothelial homeostasis and to
      describe recently characterized molecular pathways involved. We highlight how
      structural and functional modifications of HDL particles in patients with CAD may
      perturb the physiological homeostasis and lead to a loss of endothelial
      protective properties of HDL in patients with CAD. 

PMID- 24935433
TI  - Leucocyte expression of complement C5a receptors exacerbates infarct size after
      myocardial reperfusion injury.
AB  - AIMS: Early reperfusion is mandatory for the treatment of acute myocardial
      infarction. This process, however, also induces additional loss of viable
      myocardium, called ischaemia-reperfusion (IR) injury. Complement activation plays
      an important role in IR injury, partly through binding of C5a to its major
      receptor (C5aR). We investigated the role of C5aR on infarct size and cardiac
      function in a model for myocardial IR injury. METHODS AND RESULTS: BALB/c (WT)
      mice and C5aR(-/-) mice underwent coronary occlusion for 30 min, followed by
      reperfusion. Infarct size, determined 24 h after IR, was reduced in C5aR(-/-)
      mice compared with WT mice (28.5 +/- 2.1 vs. 35.7 +/- 2.5%, P = 0.017). Bone
      marrow (BM) chimaera experiments showed that this effect was due to the absence
      of C5aR on circulating leucocytes, since a similar reduction in infarct size was
      observed in WT mice with C5aR-deficient BM cells (25.3 +/- 2.2 vs. 34.6 +/- 2.8%,
      P < 0.05), but not in C5aR(-/-) mice with WT BM cells. Reduced infarct size was
      associated with fewer neutrophils, T cells, and macrophages in the infarcted area
      24 h after IR in C5aR(-/-) mice, and also with lower levels of Caspase-3/7
      indicating less inflammation and apoptosis. Echocardiography 4 weeks after IR
      showed an improved ejection fraction in C5aR(-/-) mice (25.8 +/- 5.5 vs. 19.2 +/-
      5.4%, P < 0.001). CONCLUSION: The absence of C5aR on circulating leucocytes
      reduces infarct size, is associated with reduced leucocyte infiltration and with
      less apoptosis in the infarcted myocardium, and improves cardiac function in a
      mouse model of myocardial IR injury. Selective blocking of C5aR might be a
      promising strategy to prevent myocardial IR injury.

PMID- 24935434
TI  - HDL-mediated mechanisms of protection in cardiovascular disease.
AB  - Low plasma levels of HDL-cholesterol (HDL-C) represent a strong and independent
      risk factor for cardiovascular disease. HDL particles display a wide spectrum of
      atheroprotective activities, which include effluxing cellular cholesterol,
      diminishing cellular death, decreasing vascular constriction, reducing
      inflammatory response, protecting from pathological oxidation, combating
      bacterial infection, lessening platelet activation, regulating gene expression by
      virtue of microRNAs, and improving glucose metabolism. It remains presently
      indeterminate as to whether some biological activities of HDL are more relevant
      for the protection of the endothelium from atherogenesis when compared with
      others. The multitude of such activities raises the question of a proper assay to
      assess HDL functionality ex vivo. Together with clear understanding of molecular
      mechanisms underlying atheroprotective properties of HDL, such assay will provide
      a basis to resolve the ultimate question of the HDL field to allow the
      development of efficient HDL-targeting therapies. 

PMID- 24935431
TI  - Emerging roles of junctophilin-2 in the heart and implications for cardiac
      diseases.
AB  - Cardiomyocytes rely on a highly specialized subcellular architecture to maintain
      normal cardiac function. In a little over a decade, junctophilin-2 (JPH2) has
      become recognized as a cardiac structural protein critical in forming junctional
      membrane complexes (JMCs), which are subcellular domains essential for excitation
      contraction coupling within the heart. While initial studies described the
      structure of JPH2 and its role in anchoring junctional sarcoplasmic reticulum and
      transverse-tubule (T-tubule) membrane invaginations, recent research has an
      expanded role of JPH2 in JMC structure and function. For example, JPH2 is
      necessary for the development of postnatal T-tubule in mammals. It is also
      critical for the maintenance of the complex JMC architecture and stabilization of
      local ion channels in mature cardiomyocytes. Loss of this function by mutations
      or down-regulation of protein expression has been linked to hypertrophic
      cardiomyopathy, arrhythmias, and progression of disease in failing hearts. In
      this review, we summarize current views on the roles of JPH2 within the heart and
      how JPH2 dysregulation may contribute to a variety of cardiac diseases. 

PMID- 24935435
TI  - Analysis of suspected wildlife crimes submitted for forensic examinations in
      Scotland.
AB  - This study describes the occurrence of suspected wildlife crimes submitted for
      forensic examination in Scotland in 2010. The study aims were to determine which
      types of crimes were committed, which species were targeted, and the outcome of
      investigations, in order to assess the contribution of forensic examinations in
      the prosecution of wildlife crimes. Information on suspected wildlife crimes
      submitted between January 1 and December 31, 2010 to the SAC Consulting:
      Veterinary Services Disease Surveillance Centers, Science and Advice for Scottish
      Agriculture, and to the University of Glasgow, was used. The location of
      suspected crimes, the species targeted, cause of death, and types of the 188
      submitted wildlife crimes were summarized. More information regarding cases
      involving birds were submitted than cases involving mammals, and included 114
      raptors, 14 waterfowl, and 22 "other bird species." Mammal cases (n = 38)
      included 12 badgers, 8 foxes, 7 deer, 4 hares, and 7 "other mammals." The cause
      of death was determined in 124 suspected crimes; malicious or accidental trauma
      was the most likely cause of death in 72, and 33 were poisoned. Forensic evidence
      supporting criminal activity was found in 53 cases, and poisoning was the most
      frequent crime recorded. At least five individuals were successfully prosecuted,
      representing 2.7 % of submissions. It was challenging to track cases from
      submission through to prosecution and laboratories conducting forensic
      investigations were often not informed of the outcome of prosecutions or court
      decisions. 

PMID- 24935436
TI  - Can early myocardial infarction-related deaths be diagnosed using postmortem
      urotensin receptor expression levels?
AB  - PURPOSE: Myocardial infarction (MI) is one of the most prevalent causes of sudden
      adult death. It is difficult to diagnose early MI postmortem because there are no
      typical or characteristic changes in morphology. In this study, changes in the
      level of the mRNA for the urotensin receptor (UR) were investigated postmortem to
      determine the suitability of UR as a biomarker for diagnosis of early MI after
      death. METHODS: An MI rat model was developed by injecting rats with
      isoproterenol (ISO) (lethal dose 850 mg/kg) or normal saline (control group). The
      hearts of rats in the control and ISO-induced MI groups were harvested at 0, 1,
      3, 6, 12, 24, 48, and 72 h (h) postmortem. The hearts were then immediately
      submerged in 1 mL of RNA stabilization solution and stored at 4  degrees C for <1
      week before RNA extraction. Relative UR expression analysis was performed using
      the StepOne Plus Real Time PCR System with cDNA synthesized from rat heart.
      RESULTS: Postmortem UR mRNA expression was higher in the ISO-induced MI group
      than in the control group, at both 4 and 20  degrees C, at all of the time points
      examined except 72 h postmortem (p < 0.0001). The largest increases were observed
      at ambient temperature and 6 h postmortem. CONCLUSIONS: Based on our findings,
      increased postmortem UR expression could serve as a biomarker to aid diagnosis of
      early MI.

PMID- 24935437
TI  - Simultaneous determination of seven ginsenosides in rat plasma by high
      performance liquid chromatography coupled to time-of-flight mass spectrometry:
      application to pharmacokinetics of Shenfu injection.
AB  - A high-performance liquid chromatography coupled to time-of-flight mass
      spectrometry (HPLC-TOF MS) method was successfully developed and validated for
      the identification and determination of seven ginsenosides, Re , Rf , Rb1 , Rc ,
      Rb2 , Ro and Rd , in a Chinese herbal preparation, Shenfu injection, and rat
      plasma. Based on the method, the pharmacokinetic profiles of the seven
      ginsenosides were investigated following intravenous administration of single
      dose of Shenfu injection to six rats. The established method had high linearity,
      selectivity, sensitivity, accuracy and precision. The pharmacokinetic results
      showed that Rb1 , Rc and Rb2 had similar pharmacokinetic profiles and relatively
      long half-life values (19.29 +/- 6.36, 29.54 +/- 22.91 and 35.60 +/- 30.66 h).
      The half-lives of Rf and Rd were 4.21 +/- 3.68 and 8.49 +/- 5.20 h, respectively,
      indicating that they could be metabolized more rapidly than Rb1 , Rc and Rb2 .

PMID- 24935439
TI  - The interplay between intuitive psychology and intuitive sociology.

PMID- 24935438
TI  - Impact of obesity on mammary gland inflammation and local estrogen production.
AB  - Obesity rates have risen dramatically over the past century, having nearly
      doubled since 1980. Changes in diet and lifestyle have contributed to this
      occurrence in younger women, and changing hormone levels during the menopausal
      transition has no doubt exacerbated the issue in older women. The relationship
      between adiposity and breast cancer is clear in postmenopausal women, and is
      intimately linked to the increased expression of aromatase and the production of
      estrogens within the breast adipose. This, in turn, is highly dependent on the
      localized chronic inflammation observed in obese adipose. This review will
      therefore explore the relationship between obesity, inflammation and estrogens,
      with a particular focus on the molecular regulation of aromatase in the
      postmenopausal breast in the context of obesity and breast cancer. 

PMID- 24935441
TI  - Determinants and prevalence of e-cigarette use throughout the European Union: a
      secondary analysis of 26 566 youth and adults from 27 Countries.
AB  - OBJECTIVE: This study assessed the prevalence and determinants of e-cigarette use
      among persons aged >=15 years in 27 European Union (EU) member countries during
      2012. METHODS: The 2012 Eurobarometer 385 (77.1) survey was analysed for n=26 566
      respondents. Knowledge, perception of harm, and determinants of e-cigarettes use
      were assessed, while separate regression analyses among current (n=7352) and
      former cigarette smokers (n=5782) were performed. National estimates of the
      number of e-cigarette users were also extrapolated. RESULTS: 20.3% of current
      smokers, 4.7% of ex-smokers, and 1.2% of never cigarette smokers in the EU
      reported having ever used an e-cigarette (overall approximately 29.3 million
      adults). Among smokers, ever e-cigarette use was more likely among 15-24-year
      olds (aOR 3.13, 95% CI 2.22 to 4.54) and 25-39-year-olds (aOR 2.00, 95% CI 1.47
      to 2.78) in comparison to older smokers, and among those who smoked 6-10
      cigarettes/day (aOR 1.53, 95% CI 1.10 to 2.13) or 11-20 cigarettes/day (aOR 2.07,
      95% CI 1.52 to 2.81) in comparison to very light smokers (<=5 cigarettes/day).
      Moreover, e-cigarette use was more likely among smokers who had made a past year
      quit attempt (aOR 2.08, 95% CI 1.67 to 2.58). E-cigarette use among ex-smokers
      was associated only with the respondents' age, with younger ex-smokers being more
      likely to have ever used an e-cigarette. CONCLUSIONS: A substantial number of EU
      adults have ever used e-cigarettes. Ever users were more likely to be younger,
      current smokers, or past-year quit attempters. These findings underscore the need
      to evaluate the potential long term impact of e-cigarette use on consumer health,
      cessation and nicotine addiction and formulate a European framework for e
      cigarette regulation within the revised EU Tobacco Product Directive.

PMID- 24935440
TI  - Cytotoxicity of the Vibrio vulnificus MARTX toxin effector DUF5 is linked to the
      C2A subdomain.
AB  - The multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are bacterial
      protein toxins that serve as delivery platforms for cytotoxic effector domains.
      The domain of unknown function in position 5 (DUF5) effector domain is present in
      at least six different species' MARTX toxins and as a hypothetical protein in
      Photorhabdus spp. Its presence increases the potency of the Vibrio vulnificus
      MARTX toxin in mouse virulence studies, indicating DUF5 directly contributes to
      pathogenesis. In this work, DUF5 is shown to be cytotoxic when transiently
      expressed in HeLa cells. DUF5 localized to the plasma membrane dependent upon its
      C1 domain and the cells become rounded dependent upon its C2 domain. Both full
      length DUF5 and the C2 domain caused growth inhibition when expressed in
      Saccharomyces cerevisiae. A structural model of DUF5 was generated based on the
      structure of Pasteurella multocida toxin facilitating localization of the
      cytotoxic activity to a 186 amino acid subdomain termed C2A. Within this
      subdomain, an alanine scanning mutagenesis revealed aspartate-3721 and arginine
      3841 as residues critical for cytotoxicity. These residues were also essential
      for HeLa cell intoxication when purified DUF5 fused to anthrax toxin lethal
      factor was delivered cytosolically. Thermal shift experiments indicated that
      these conserved residues are important to maintain protein structure, rather than
      for catalysis. The Aeromonas hydrophila MARTX toxin DUF5(Ah) domain was also
      cytotoxic, while the weakly conserved C1-C2 domains from P. multocida toxin were
      not. Overall, this study is the first demonstration that DUF5 as found in MARTX
      toxins has cytotoxic activity that depends on conserved residues in the C2A
      subdomain.

PMID- 24935442
TI  - Economic evaluation of a hospital-initiated intervention for smokers with chronic
      disease, in Ontario, Canada.
AB  - INTRODUCTION: Cigarette smoking causes many chronic diseases that are costly and
      result in frequent hospitalisation. Hospital-initiated smoking cessation
      interventions increase the likelihood that patients will become smoke-free. We
      modelled the cost-effectiveness of the Ottawa Model for Smoking Cessation (OMSC),
      an intervention that includes in-hospital counselling, pharmacotherapy and
      posthospital follow-up, compared to usual care among smokers hospitalised with
      acute myocardial infarction (AMI), unstable angina (UA), heart failure (HF), and
      chronic obstructive pulmonary disease (COPD). METHODS: We completed a cost
      effectiveness analysis based on a decision-analytic model to assess smokers
      hospitalised in Ontario, Canada for AMI, UA, HF, and COPD, their risk of
      continuing to smoke and the effects of quitting on re-hospitalisation and
      mortality over a 1-year period. We calculated short-term and long-term cost
      effectiveness ratios. Our primary outcome was 1-year cost per quality-adjusted
      life year (QALY) gained. RESULTS: From the hospital payer's perspective, delivery
      of the OMSC can be considered cost effective with 1-year cost per QALY gained of
      $C1386, and lifetime cost per QALY gained of $C68. In the first year, we
      calculated that provision of the OMSC to 15 326 smokers would generate 4689
      quitters, and would prevent 116 rehospitalisations, 923 hospital days, and 119
      deaths. Results were robust within numerous sensitivity analyses. DISCUSSION: The
      OMSC appears to be cost-effective from the hospital payer perspective. Important
      consideration is the relatively low intervention cost compared to the reduction
      in costs related to readmissions for illnesses associated with continued smoking.

PMID- 24935443
TI  - What characterises smokers who quit without using help? A study of users and non
      users of cessation support among successful ex-smokers.
AB  - BACKGROUND: A variety of smoking cessation aids are available; however, the
      majority of smokers quit unaided. We know little of the differences between users
      and non-users of cessation support. METHODS: A cross-sectional study based on the
      Danish Health Examination Survey (DANHES) conducted in 2007-2008. In all, 6445
      persons reporting quitting successfully within the last 5 years were included in
      analyses. Users and non-users of cessation aid (medical or behavioural support)
      were compared with regards to age, education, years smoked, tobacco amount,
      tobacco type and smoking-related disease using logistic regression analysis.
      RESULTS: Quitting unaided was reported by 63%. Adjusted analyses showed that men
      were more likely to quit unaided than women, and younger compared with older were
      more likely to quit unaided (eg, OR among women age 45-59 versus age 14-29 were
      0.18, 95% CI 0.12 to 0.20). Additionally, those who had smoked for 15 years or
      more also had lower odds of quitting unaided. Smoking 15 or more grams of tobacco
      daily was inversely associated with quitting unaided (eg, OR among men were 0.38,
      95% CI 0.31 to 0.46). CONCLUSIONS: Quitting smoking without the use of formalised
      aid was the most common cessation approach. Quitting unaided was more likely
      among men, younger age groups, those with a shorter history of smoking and those
      who were light smokers. These results indicate that awareness of unaided
      cessation in general and to those for whom it is especially relevant should be
      increased. This could lead to a more efficient use of resources for cessation
      support.

PMID- 24935444
TI  - An emerging role: the nurse content curator.
AB  - A new phenomenon, the inverted or "flipped" classroom, assumes that students are
      no longer acquiring knowledge exclusively through textbooks or lectures. Instead,
      they are seeking out the vast amount of free information available to them online
      (the very essence of open source) to supplement learning gleaned in textbooks and
      lectures. With so much open-source content available to nursing faculty, it
      benefits the faculty to use readily available, technologically advanced content.
      The nurse content curator supports nursing faculty in its use of such content.
      Even more importantly, the highly paid, time-strapped faculty is not spending an
      inordinate amount of effort surfing for and evaluating content. The nurse content
      curator does that work, while the faculty uses its time more effectively to help
      students vet the truth, make meaning of the content, and learn to problem-solve.
      Brooks. 

PMID- 24935445
TI  - Low risk papillary thyroid cancer.
AB  - Thyroid cancer is one of the fastest growing diagnoses; more cases of thyroid
      cancer are found every year than all leukemias and cancers of the liver,
      pancreas, and stomach. Most of these incident cases are papillary in origin and
      are both small and localized. Patients with these small localized papillary
      thyroid cancers have a 99% survival rate at 20 years. In view of the excellent
      prognosis of these tumors, they have been denoted as low risk. The incidence of
      these low risk thyroid cancers is growing, probably because of the use of imaging
      technologies capable of exposing a large reservoir of subclinical disease.
      Despite their excellent prognosis, these subclinical low risk cancers are often
      treated aggressively. Although surgery is traditionally viewed as the cornerstone
      treatment for these tumors, there is less agreement about the extent of surgery
      (lobectomy v near total thyroidectomy) and whether prophylactic central neck
      dissection for removal of lymph nodes is needed. Many of these tumors are treated
      with radioactive iodine ablation and thyrotropin suppressive therapy, which
      although effective for more aggressive forms of thyroid cancer-have not been
      shown to be of benefit in the management of these lesions. This review offers an
      evidence based approach to managing low risk papillary thyroid cancer. It also
      looks at the future of promising alternative surgical techniques, non-surgical
      minimally localized invasive therapies (ethanol ablation and laser ablation), and
      active surveillance, all of which form part of a more individualized treatment
      approach for low risk papillary thyroid tumors. 

PMID- 24935446
TI  - Interleukin-6 and neopterin levels in the serum and saliva of patients with
      Lichen planus and oral Lichen planus.
AB  - BACKGROUND: Lichen planus together with its oral variant is a chronic,
      inflammatory disease of the skin and the mucosa of unclear aetiology and with an
      unpredictable course that still poses a major problem in terms of diagnosis and
      treatment. The objective of this study was to assess the concentrations of
      interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen
      planus (including reticular and erosive form of oral lichen planus) and to
      compare them with the concentrations observed in healthy controls. METHODS: The
      study material comprised serum and saliva samples from 56 patients diagnosed with
      lichen planus and 56 healthy volunteers. The ELISA test was used to measure
      concentrations of IL-6 and neopterin in the serum and saliva of the study
      participants. RESULTS: The concentrations of IL-6 in saliva and serum of patients
      with lichen planus were significantly higher than in controls (P = 0.0002; P <
      0.0001). The difference remains significant after adjustment for gingivitis and
      age. Patients with atrophic-erosive oral lichen planus had significantly higher
      IL-6 concentrations in their saliva compared to patients with reticular form of
      disease (P = 0.01). The concentrations of neopterin were significantly higher in
      the serum but not in saliva of lichen planus patients vs. controls (P <0.0001).
      CONCLUSIONS: Serum levels of proinflammatory cytokines IL-6 and neopterin are
      increased in lichen planus as well as the salivary concentrations of IL-6. The
      differences observed in IL-6 levels in patients with erosive-atrophic forms of
      oral lichen planus may indicate a substantial role played by the cytokine in the
      disease.

PMID- 24935447
TI  - [Written personalized action plan for atopic dermatitis: a patient education
      tool].
AB  - Atopic dermatitis (AD) is the most frequent children's chronic skin disease.
      Management of AD can be difficult because local treatments must be adapted to the
      skin's condition. Between consultations, sudden changes in the state of the
      disease can make it difficult to manage local treatment. Parents and children
      need information that will help them adapt their treatment to the course of their
      disease. Aiming to enable parents to better treat their atopic child by
      themselves, we have developed a personalized action plan in order to simplify,
      personalize, and adapt the medical prescription to the state of the disease. The
      Personalized Written Action Plan for Atopics (PA2P) is based on the model used in
      the treatment of asthma, with integrated specificities for AD in children. The
      aim of this study was to assess the feasibility and pertinence of the PA2P for
      pediatricians to use in private practice. A total of 479 pediatricians answered a
      questionnaire sent by e-mail. The vast majority of the respondents gave positive
      reviews of the tool: 99% of the pediatricians declared the tool to be pertinent,
      qualifying it as clear and logical. The PA2P appeared to be appropriate for the
      atopic patient because it improves the families' involvement in the application
      of local treatment by offering personalized care and by simplifying the doctor's
      prescription. Finally, 72% of doctors responding to the questionnaire were
      willing to take part in future studies involving parents. More than a gadget, the
      PA2P could become a useful tool for therapeutic patient education.

PMID- 24935448
TI  - [A 2-month-old baby with Mediterranean spotted fever].
AB  - INTRODUCTION: Mediterranean spotted fever is an endemic rickettsiosis in southern
      France. We report here the case of a 2-month-old baby who developed rickettsiosis
      after a tick bite. CLINICAL FACT: A 2-month-old baby was hospitalized in the
      pediatric ward for fever with maculopapular rash extending to the palms and
      plantar surfaces and an eschar after a tick bite. Rickettsiosis serology examined
      after 48 h of fever was negative, but Rickettsia (spotted group) PCR taken from
      the lesion at the bite site was positive. A 1-week treatment with clarithromycin
      was started. Fever and rash disappeared 3 days after treatment initiation.
      DISCUSSION: Mediterranean spotted fever is endemic in southern France. It is,
      therefore, important to consider this diagnosis and search for tick bite signs or
      an eschar when a patient presents with fever and maculopapular rash. The
      treatment of choice consists in doxycycline or macrolides. CONCLUSION: Around the
      Mediterranean sea in particular, Mediterranean spotted fever should be considered
      as a possible cause of febrile disease with rash, to allow for a specific
      antibiotic treatment as fast as possible and to avoid dangerous complications,
      even though few cases have been reported below the age of 3 months.

PMID- 24935449
TI  - [Pulmonary actinomycosis with chest wall fistula formation in a child].
AB  - INTRODUCTION: Actinomycosis is a suppurative infection caused by bacteria of the
      Actinomyces genus. It is a rare cause of pulmonary infection and can be difficult
      to diagnose because its presentation may mimic tuberculosis or cancer. In the
      absence of treatment of pulmonary lesions fistulae can develop. We report a case
      of thoracic actinomycosis with chest wall involvement in a child, managed in the
      pediatric department at Moulay Youssef University Hospital in Rabat, Morocco.
      CASE REPORT: We report the case of a 13-year-old boy with a history of trauma to
      the right chest 1 year earlier, admitted with right-sided chest wall swelling
      with cutaneous fistulae. Physical examination identified a parietal mass with
      fistulization to the skin. Laboratory tests showed an inflammatory syndrome. The
      chest x-ray revealed moderate right pleural effusion. The thoracic computed
      tomography scan showed a right parietal pleural mass and the percutaneous biopsy
      confirmed the diagnosis of actinomycosis. The patient underwent antibiotic
      therapy with favorable evolution. CONCLUSION: The diagnosis, the clinical,
      radiological and histological pattern, and the therapeutic features are described
      in this report.

PMID- 24935450
TI  - [BCG multifocal osteomyelitis. A case report].
AB  - Multifocal osteomyelitis is a rare complication of the Bacille Calmette-Guerin
      (BCG) vaccine. It particularly affects immunocompromised children and poses a
      difficult diagnostic problem. A 6-month-old boy had BCG vaccination postnatally
      and developed extensive disseminated skeletal osteomyelitis. He was found to have
      severe combined immunodeficiency. Despite antibiotic therapy and bone marrow
      grafting, the disease was fatal. 

PMID- 24935451
TI  - [Serratia marcescens osteomyelitis as the first manifestation of chronic
      granulomatous disease].
AB  - Chronic granulomatous disease is a rare, primary immunodeficiency disorder
      characterized by a defect in oxidative metabolism in phagocytes and recurrent
      bacterial and fungal infections. We report a case in a 2-month-old infant
      admitted with metacarpic osteomyelitis due to Serratia marcescens. Chronic
      granulomatous disease is rare but must be considered in cases of uncommon or
      atypical infection. 

PMID- 24935452
TI  - [Childhood psoriasis].
AB  - Psoriasis is a chronic inflammatory skin disease that can affect nearly 1% of
      children, even during the first months of life. Recently, a link with obesity has
      been demonstrated by a few studies. The most common clinical form is the plaque
      psoriasis type, which only affects 50% of children. Napkin psoriasis, guttate
      psoriasis, and palmoplantar keratoderma appear to have specific aspects in
      childhood. Although benign, the social impact induced by psoriasis can be major,
      especially in children, if the disease is poorly understood or inadequately
      treated. First-line treatment should always include local treatments. In severe
      cases as assessed by clinical appearance or impact on quality of life, initiation
      of systemic treatments should not be delayed. 

PMID- 24935453
TI  - [New recommendations for the management of children after minor head trauma].
AB  - Minor head trauma is a common cause for pediatric emergency department visits. In
      2009, the Pediatric Emergency Care Applied Research Network (PECARN) published a
      clinical prediction rule for identifying children at very low risk of clinically
      important traumatic brain injuries (ciTBI) and for reducing CT use because of
      malignancy induced by ionizing radiation. The prediction rule for ciTBI was
      derived and validated on 42,412 children in a prospective cohort study. The
      Societe Francaise de Medecine d'Urgence (French Emergency Medicine Society) and
      the Groupe Francophone de Reanimation et Urgences Pediatriques (French-Language
      Pediatric Emergency Care Group) recommend this algorithm for the management of
      children after minor head trauma. Based on clinical variables (history, symptoms,
      and physical examination findings), the algorithm assists in medical decision
      making: CT scan, hospitalization for observation or discharge, according to three
      levels of ciTBI risk (high, intermediate, or low risk). The prediction rule
      sensitivity for children younger than 2 years is 100 % [86.3-100] and for those
      aged 2 years and older it is 96.8 % [89-99.6]. Our aim is to present these new
      recommendations for the management of children after minor head trauma.

PMID- 24935454
TI  - [Hereditary hemorrhagic telangiectasia. Report of a pediatric case].
AB  - Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber syndrome, is an
      autosomal dominant multiorgan disorder. This multisystemic vascular dysplasia is
      determined by a mutation of one of two main genes, endoglin (ENG) or HHT1, or
      ACVRL1 or HHT2. These mutations induce vascular disorders that cause recurrent
      epistaxis and eventually multiple telangiectasia and arteriovenous visceral
      malformations. We report the case of a 7-year-old girl who developed severe
      hypoxemia due to multiple pulmonary arteriovenous malformations. 

PMID- 24935455
TI  - [Hyperimmunoglobulinemia D and periodic fever syndrome].
AB  - We report the cases of two sisters born of parents who were first-degree cousins,
      who started recurrent fever with lymph node and digestive tract involvement at
      the age of 2 years. There was no mutation of the familial Mediterranean fever
      gene and a diagnosis of partial mevalonate kinase (MVK) deficiency was made.
      However, immunoglobulin (Ig) D and A levels were normal. Elevated mevalonic acid
      in the patients' urine during an episode and MVK gene analysis provided the
      diagnosis. Clinical remission was obtained under anti-TNF-alpha treatment with
      etanercept. These observations and those of several previously reported patients,
      particularly in French and Dutch series, illustrate the importance of considering
      the diagnosis in a child with early-onset auto-inflammatory syndrome even in the
      absence of hyper-IgD or -IgA. 

PMID- 24935456
TI  - Upregulation of store-operated Ca(2+) entry in the naive CD4(+) T cells with
      aberrant cytokine releasing in active rheumatoid arthritis.
AB  - The regulated control of Ca(2+) influx is essential for the activation and
      function of the adaptive immune response, as Ca(2+) is a key regulator of
      important transcription factors. To determine whether Ca(2+) release-activated
      Ca(2+) (CRAC) channels contribute to the abnormal behaviour of T cells in
      patients with rheumatoid arthritis (RA), we performed a cross-sectional study to
      characterize the expression and functional status of CRACM1 channels in RA
      patients. Peripheral blood was obtained from 50 RA patients, 50 osteoarthritis
      (OA) patients and healthy donors. We measured Ca(2+) influx and CRAC currents in
      naive and memory CD4(+) T cells. CRACM1 expression was evaluated in T cells from
      each of the three groups. These cells were further characterized by flow
      cytometric analysis of interleukin-4 (IL-4), IL-17, interferon-gamma and tumour
      necrosis factor-alpha. These cytokines were also measured in naive CD4(+) T cells
      following the lentivirus-mediated silencing of CRACM1.There was a significant
      positive correlation between Ca(2+) influx in naive T cells and RA activity.
      Functionally aberrant naive CD4(+) T cells from patients with active RA showed
      the different cytokine release pattern and exhibited increased Ca(2+) influx as
      well as increased CRACM1 protein expression and function. Specific lentiviral
      induced gene silencing of CRACM1 reversed the alterations in T-cell cytokine
      production. The data presented here indicate that an upregulation of CRACM1
      expression and function may be responsible for the abnormal cytokine release of
      naive CD4(+) T cells in RA patients. CRACM1 might therefore represent a new
      molecular target for RA therapies. 

PMID- 24935457
TI  - In vivo functional mapping of the conserved protein domains within murine
      Themis1.
AB  - Thymocyte development requires the coordinated input of signals that originate
      from numerous cell surface molecules. Although the majority of thymocyte signal
      initiating receptors are lineage-specific, most trigger 'ubiquitous' downstream
      signaling pathways. T-lineage-specific receptors are coupled to these signaling
      pathways by lymphocyte-restricted adapter molecules. We and others recently
      identified a new putative adapter protein, Themis1, whose expression is largely
      restricted to the T lineage. Mice lacking Themis1 exhibit a severe block in
      thymocyte development and a striking paucity of mature T cells revealing a
      critical role for Themis1 in T-cell maturation. Themis1 orthologs contain three
      conserved domains: a proline-rich region (PRR) that binds to the ubiquitous
      cytosolic adapter Grb2, a nuclear localization sequence (NLS), and two copies of
      a novel cysteine-containing globular (CABIT) domain. In the present study, we
      evaluated the functional importance of each of these motifs by retroviral
      reconstitution of Themis1(-/-) progenitor cells. The results demonstrate an
      essential requirement for the PRR and NLS motifs but not the conserved CABIT
      cysteines for Themis1 function. 

PMID- 24935459
TI  - B cells take their time: sequential IgG class switching over the course of an
      immune response?

PMID- 24935458
TI  - CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific
      antibody.
AB  - Blockade of CD44 is considered a therapeutic option for the elimination of
      leukemia-initiating cells. However, the application of anti-panCD44 can be
      burdened by severe side effects. We determined whether these side effects could
      be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific
      antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and
      CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4
      v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies,
      respectively. Ex vivo analysis indicated that natural killer cytotoxicity and
      antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under
      local inflammation, the efficacy of anti-CD44v10 prolonged the survival time
      twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to
      inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4
      v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell
      activation. Taken together, in hematological malignancies expressing CD44v, anti
      panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy.
      Furthermore, CD44v10-specific antibodies appear particularly advantageous in
      cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte
      recruitment and activation. 

PMID- 24935460
TI  - Peer support for stroke survivors: a case study.
AB  - BACKGROUND: Innovative and sustainable programs are required to support the well
      being of stroke survivors. Peer support is a potentially low cost way to enhance
      well-being of recent stroke survivors and the well-being and community
      reintegration of their peer supporters. This article describes the perceptions of
      stroke survivors, care partners, peer supporters, and professionals of an
      individual peer support program. METHODS: An instrumental case study design was
      used to examine a volunteer peer support program that provides acute care visits
      and telephone follow-up post-discharge. In particular, a) type of support
      provided, b) benefits for the stroke survivor and care partner, c) potential
      harms to the stroke survivor, d) impact of providing support on the peer
      supporter, and e) required processes were considered. Semi-structured interviews
      were carried out with 16 new stroke survivors and 8 care partners immediately
      following hospital discharge and then 6 months later, and with 7 peer supporters,
      3 program co-ordinators and 4 health professionals to gather feedback from
      multiple stakeholders. RESULTS: Emotional, affirmational and informational
      support were perceived as being offered by the peer supporters. Peer visits were
      perceived as providing encouragement, motivation, validation, and decreased
      feelings of being alone. However, the visits were not perceived as beneficial to
      all stroke survivors. The impact on the peer supporters included increased social
      connections, personal growth, enjoyment, and feelings of making a difference in
      the lives of others. Involvement of the healthcare team, peer supporter training
      and a skilled coordinator were crucial to the success this program. CONCLUSIONS:
      Peer support can potentially enhance service to stroke survivors and promote
      community reintegration for peer volunteers. Further research is needed to
      determine the preferred format and timing of peer support, and the
      characteristics of stroke survivors most likely to benefit.

PMID- 24935461
TI  - Emerging themes in the development of prospective memory during childhood.

PMID- 24935463
TI  - Does pregnancy alter the long-term course of multiple sclerosis?
AB  - PURPOSE: The purpose was to examine the impact of pregnancy on the rates of
      relapses, progression to irreversible disability, and transition to secondary
      progressive multiple sclerosis (SPMS) in patients with relapsing-remitting
      multiple sclerosis (RRMS). METHODS: We retrospectively followed two subcohorts of
      women with RRMS: pregnant (n = 254) and nonpregnant (n = 423). We obtained data
      on demographic, lifestyle, and clinical characteristics from patient records.
      Poisson and logistic regressions estimated the rate ratios associated with
      pregnancy as a function of time. Confounding was controlled by propensity-score
      adjustment, and postbaseline selection bias was controlled by inverse probability
      weighting. RESULTS: In the pregnant and nonpregnant subcohorts, respectively, 300
      and 787 relapses, 15 and 27 transitions to SPMS, and 11 and 34 progressions to
      irreversible disability were documented. Adjusted rate ratios (95% confidence
      intervals) shortly after baseline were 0.67 (0.49; 0.92) for relapses, 0.16
      (0.03; 0.79) for irreversible disability, and 1.25 (0.39; 3.96) for SPMS. The
      corresponding estimates at 5 and 10 years were, respectively, 1.04 (0.72; 1.52),
      0.82 (0.36; 1.88), and 2.33 (1.03; 5.26) and 1.62 (0.84; 3.14), 4.14 (0.89;
      19.22), and 4.33 (1.10; 16.99). CONCLUSIONS: Pregnancy likely ameliorates the
      short-term course of RRMS in terms of the rates of relapses and progression to
      irreversible disability. Over the long term, it appears to have no material
      impact on these outcomes, and might in fact accelerate the rate of transition to
      SPMS.

PMID- 24935462
TI  - Changes in the prevalence of mood and anxiety disorders among male and female
      current smokers in the United States: 1990-2001.
AB  - PURPOSE: The present study investigated whether the prevalence of mood and
      anxiety disorders has increased over time among current smokers and whether these
      trends differ by gender and in comparison with nonsmokers. METHODS: Data were
      drawn from the National Comorbidity Survey (1990) and the National Comorbidity
      Survey-Replication (2001), representative samples of the US adult population.
      Binomial regression analyses were used to determine differences between mood and
      anxiety disorders among current smokers in 1990 and 2001 and whether these
      differed by gender and in comparison with those who were former or never current
      smokers. RESULTS: Any anxiety disorder, panic attacks, panic disorder, social
      anxiety disorder and dysthymia were all significantly more common among current
      smokers in 2001 compared with 1990 and except for social anxiety disorder these
      increases were significantly greater than any trend found in non-smokers.
      Increases in panic attacks, social anxiety disorder, and dysthymia were more
      pronounced in female than in male smokers. Major depressive disorder and
      generalized anxiety disorder were not found to increase over time among smokers.
      CONCLUSIONS: The prevalence of several anxiety disorders and dysthymia among
      current smokers appears to have increased from 1990 to 2001. Future studies are
      needed to determine whether these trends have continued. If so, interventions
      aimed at moving the prevalence lower may have limited success if treatment of
      mental health problems such as anxiety disorders and certain mood disorders are
      not considered in the development and dissemination of tobacco control programs.

PMID- 24935464
TI  - Utilization of glucose, blood pressure, and lipid lowering medications among
      people with type II diabetes in the United States, 1999-2010.
AB  - PURPOSE: Changes in relation to drug treatment to various control targets for
      diabetes were studied using the National Health and Nutrition Examination Survey,
      1999-2010. METHODS: Data on 3094 participants aged 20 years or older with
      diagnosed type II diabetes were analyzed. Use of medications for lowering
      glucose, blood pressure, and lipids in the past month was assessed by
      questionnaire. Data from two survey cycles were combined together to produce
      estimates for each 4-year period. RESULTS: Usage of metformin increased from
      34.8% to 53.8% and was the most prevalent medications during this period (P <
      .001), and half of subjects taking metformin could achieve glycated hemoglobin
      less than 7.0% in 2007-2010. Dipeptidyl peptidase-4 inhibitors were used by 7.4%
      of participants in 2007-2010. Usage of angiotensin receptor blockers and beta
      blockers increased significantly from 7.4% to 21.4% and from 15.3% to 31.8%,
      respectively from 1999 to 2010 (P <= .001). A total of 64.7% of participants
      could attain blood pressure control by 2007-2010. Usage of statins doubled in
      1999-2010 and 52.2% of subjects took statins by 2007-2010 (P < .001).
      CONCLUSIONS: Metformin is the first-line drug for diabetes while dipeptidyl
      peptidase-4 inhibitors started to be used since 2007. Blood pressure control
      improved in 1999-2010 partly due to increased drug prescriptions. Although
      statins were widely used about half of the participants did not take them.

PMID- 24935466
TI  - Explaining the association between educational level and frailty in older adults:
      results from a 13-year longitudinal study in the Netherlands.
AB  - PURPOSE: The aim of this study was to examine the longitudinal association
      between educational level and frailty prevalence in older adults and to
      investigate the role of material, biomedical, behavioral, social, and mental
      factors in explaining this association. METHODS: Data over a period of 13 years
      were used from the Longitudinal Aging Study Amsterdam. The study sample consisted
      of older adults aged 65 years and above at baseline (n = 1205). Frailty was
      assessed using Fried's frailty criteria. A relative index of inequality was
      calculated for the level of education. Longitudinal logistic regression analyses
      based on multilevel modeling were performed. RESULTS: Older adults with a low
      educational level had higher odds of being frail compared with those with a high
      educational level (relative index of inequality odds ratio, 2.94; 95% confidence
      interval, 1.84-4.71). These differences persisted during 13 years of follow-up.
      Adjustment for all explanatory factors reduced the effect of educational level on
      frailty by 76%. Income, self-efficacy, cognitive impairment, obesity, and number
      of chronic diseases had the largest individual contribution in reducing the
      effect. Social factors had no substantial contribution. CONCLUSIONS: Our findings
      highlight the need for a multidimensional approach in developing interventions
      aimed at reducing frailty, especially in lower educated groups.

PMID- 24935465
TI  - Assessing validity of a depression screening instrument in the absence of a gold
      standard.
AB  - PURPOSE: We evaluated the extent to which use of a hypothesized imperfect gold
      standard, the Composite International Diagnostic Interview (CIDI), biases the
      estimates of diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9).
      We also evaluate how statistical correction can be used to address this bias.
      METHODS: The study was conducted among 926 adults where structured interviews
      were conducted to collect information about participants' current major
      depressive disorder using PHQ-9 and CIDI instruments. First, we evaluated the
      relative psychometric properties of PHQ-9 using CIDI as a gold standard. Next, we
      used a Bayesian latent class model to correct for the bias. RESULTS: In
      comparison with CIDI, the relative sensitivity and specificity of the PHQ-9 for
      detecting major depressive disorder at a cut point of 10 or more were 53.1% (95%
      confidence interval: 45.4%-60.8%) and 77.5% (95% confidence interval, 74.5%
      80.5%), respectively. Using a Bayesian latent class model to correct for the bias
      arising from the use of an imperfect gold standard increased the sensitivity and
      specificity of PHQ-9 to 79.8% (95% Bayesian credible interval, 64.9%-90.8%) and
      79.1% (95% Bayesian credible interval, 74.7%-83.7%), respectively. CONCLUSIONS:
      Our results provided evidence that assessing diagnostic validity of mental health
      screening instrument, where application of a gold standard might not be
      available, can be accomplished by using appropriate statistical methods.

PMID- 24935468
TI  - Using sociometric measures to assess nonresponse bias.
AB  - PURPOSE: Much attention has been given to the potential nonresponse bias that
      occurs in epidemiologic studies that attempt to enroll a representative sample.
      Most analyses surrounding nonrespondents focus on individual-level attributes and
      how they vary across respondents and nonrespondents. Although these attributes
      are of interest, analysis of the social network position of nonrespondents as
      defined by traditional sociometric measures (i.e., centrality and bridging) has
      not been conducted, and could provide further insights into the validity of the
      sample. METHODS: We used data from the Secunderabadi Men's Study, a whole network
      of Indian men who have sex with men (MSM) generated using cell phone contact
      lists of men approached using Time Location Cluster Sampling. Multivariable
      logistic regression was used to determine whether demographic and behavioral
      attributes and indegree (the frequency of men who have sex with men was listed
      across all cell phone contact lists) were associated with being a respondent.
      RESULTS: A total of 239 respondents were interviewed and 81 were approached but
      did not consent to the interview ("nonrespondents"). CONCLUSIONS: Respondents
      were more likely to have higher indegree than nonrespondents, adjusting for
      attribute differences (odds ratio, 1.19; 95% confidence interval, 1.07, 1.34).
      This analysis suggests that the network position of nonrespondents may be
      important when considering the potential impact of nonresponse bias.

PMID- 24935467
TI  - Disability and the built environment: an investigation of community and
      neighborhood land uses and participation for physically impaired adults.
AB  - PURPOSE: There is a need for empirical support of the association between the
      built environment and disability-related outcomes. This study explores the
      associations between community and neighborhood land uses and community
      participation among adults with acquired physical disability. METHODS: Cross
      sectional data from 508 community-living chronically disabled adults in New
      Jersey were obtained from among participants in national Spinal Cord Injury Model
      Systems database. Participants' residential addresses were geocoded to link
      individual survey data with Geographic Information Systems data on land use and
      destinations. The influence of residential density, land use mix, destination
      counts, and open space on four domains of participation were modeled at two
      geographic scales-the neighborhood (i.e., half mile buffer) and community (i.e.,
      five mile) using multivariate logistic regression. All analyses were adjusted for
      demographic- and impairment-related differences. RESULTS: Living in communities
      with greater land use mix and more destinations was associated with a decreased
      likelihood of reporting optimum social and physical activity. Conversely, living
      in neighborhoods with large portions of open space was positively associated with
      the likelihood of reporting full physical, occupational, and social
      participation. CONCLUSIONS: These findings suggest that the overall living
      conditions of the built environment may be relevant to social inclusion for
      persons with physical disabilities.

PMID- 24935469
TI  - The association of phosphatase and tensin homolog deleted on chromosome 10
      polymorphisms and lifestyle habits with colorectal cancer risk in a Chinese
      population.
AB  - The PI3K signaling pathway plays an important role in the development of
      colorectal cancer (CRC) and other neoplasm. Somatic phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN) mutations and deletions or epigenetic
      silencing have been observed in multiple tumor types including CRC. To assess the
      association of PTEN polymorphisms and lifestyle habits with CRC risk in Chinese
      population, we carried out a case-control study which included 545 cases and 522
      controls. In the present study, we genotyped eight single-nucleotide
      polymorphisms (SNPs) in PTEN and found that rs11202607 was associated with
      increased CRC risk (odds ratio (OR) = 1.40, 95 % confidence interval (CI) = 1.04
      1.90). Stratification analysis by lifestyle habits showed a stronger association
      between rs11202607 and CRC risk among never tea drinkers than that among tea
      drinkers (OR = 2.04, 95 % CI 1.29-3.22), and significant additive interaction
      between rs10490920 and tea drinking status was observed. Our study provided the
      evidence of an association between PTEN polymorphisms and the risk of CRC and
      significant additive interaction between PTEN polymorphism and tea drinking.
      Studies with larger sample size and further investigations into the mechanism are
      warranted to clarify the role of PTEN in colorectal carcinogenesis and the
      association between PTEN genetic variations, environment exposure, and CRC risk.

PMID- 24935470
TI  - Expression of survivin mRNA in gallbladder cancer: a diagnostic and prognostic
      marker?
AB  - Survivin, an inhibitor of apoptosis, has been shown to be expressed in various
      malignancies. However, its role in gallbladder cancer (GBC) has not been
      evaluated yet. We investigated its expression in peripheral blood of patients
      with gallbladder diseases (gallstone disease (GSD), n = 30; GBC, n = 39) and
      compared with healthy controls (n = 25). Survivin expression was correlated with
      clinicopathological parameters, diagnosis, and prognosis of patients with GBC.
      Expression of survivin messenger RNA (mRNA) in blood was evaluated by real-time
      PCR. Significantly higher (P < 0.0001) expression of survivin mRNA was observed
      in GBC (2.2-fold) and GSD (1.52-fold) as compared to control. In GBC, increased
      survivin expression was significantly associated with higher tumor stage (stage
      III vs. stage II; P < 0.0001) and tumor differentiation (poor and moderate vs.
      well differentiated; P < 0.0001). No significant correlation was observed with
      any of the other clinicopathological parameters (age, gender, and presence or
      absence of gallstones) studied. Cutoff value of survivin mRNA relative
      quantification (RQ) was 1.08, with a sensitivity of 98.55 % and specificity of
      100 % for the diseased group (GSD or GBC). RQ value of 1.71 differentiated GBC
      from GSD with a sensitivity of 89.74 % and specificity of 100 %. Increased
      expression of survivin was associated with a shorter median overall survival (12
      vs. 18 months) in GBC patients. Differential expression of survivin in GBC
      suggests its possible role and association with poor prognosis. Expression of
      survivin in peripheral blood could be useful both in the diagnosis and prognosis
      of GBC.

PMID- 24935471
TI  - ADAM10 regulates proliferation, invasion, and chemoresistance of bladder cancer
      cells.
AB  - A disintegrin and metalloprotease 10 (ADAM10) is upregulated in several cancers
      and associates with malignant cancer progression. However, its expression pattern
      in bladder cancer remains unexplored. In the present study, we examined ADAM10
      expression in 105 bladder cancer specimens using immunohistochemistry. We found
      ADAM10 overexpression in 51 of 105 (48.5 %) bladder cancer specimens. ADAM10
      overexpression associated with advanced tumor stage (p = 0.001) and tumor grade
      (p = 0.018). To explore its biological functions in bladder cancer cells, small
      interfering RNA (siRNA) knockdown was performed in 5,637 and T24 cell lines. Cell
      Counting Kit-8 (CCK8) assay and Matrigel invasion assay showed that ADAM10
      depletion decreased cell proliferation, migration, and invasion. In addition,
      ADAM10 knockdown increased the level of cisplatin-induced apoptosis. In
      conclusion, ADAM10 is overexpressed in bladder cancer and regulates malignant
      cell growth and invasion, which makes it a candidate therapeutic target.

PMID- 24935473
TI  - Correlations of common polymorphism of EVI-1 gene targeted by miRNA-206/133b with
      the pathogenesis of breast cancer.
AB  - The aim of this study was to identify the correlations of a common polymorphism
      (rs6774494 A > G) in the EVI-1 gene targeted by micro-RNA (miRNA)-206/133b with
      the pathogenesis of breast cancer (BC). A total of 196 unrelated ethnic Han
      Chinese women diagnosed with primary BC were consecutively recruited and 200
      healthy controls were randomly selected from the same population-based cohort.
      Direct PCR sequencing assay was used to detection of rs6774494 A > G polymorphism
      in the EVI-1 gene. Real-time quantitative PCR (RT-PCR) analysis was performed to
      verify the alterations of the EVI1 messenger RNA (mRNA) levels. Kaplan-Meier
      analysis was used to investigate and to estimate the survival outcomes for each
      endpoint. All statistical analyses were performed with SPSS software (version
      18.0, SPSS, Chicago, IL). Our results demonstrated that the carriers of EVI-1 AG
      genotype were more likely to develop BC when compared with the EVI-1 GG genotype
      (P = 0.034, OR = 1.26, 95% CI = 1.02 ~ 1.57). In addition, it was found that
      patients with the G (AG + GG) allele of EVI-1 genetic variants were associated
      with higher risk of BC compared with the EVI-1 AA genotype (OR = 1.26, 95% CI =
      1.02 ~ 1.54, P = 0.028). The results of a subgroup analysis stratified by
      menopause revealed that in female post-menopause subgroup patients with the EVI-1
      G allele were correlated with a higher risk of BC than those with the EVI-1 AA
      genotype (OR = 1.31, 95% CI = 1.00 ~ 1.72, P = 0.054). Kaplan-Meier analyses
      suggested that carriers of the G allele (AG + GG) were associated with poorer
      overall survival (OS) and progression-free survival (PFS) compared with those
      with AA genotype (OS P = 0.042; PFS P = 0.036, respectively). The correlation
      analysis showed that EVI-1 mRNA levels were negatively associated with miRNA
      206/133b levels in the carriers of the G allele (AG + GG) (r = -1.274, P < 0.05).
      Our findings provide evidence that the EVI-1 rs6774494 G > A polymorphism
      targeted by miRNA-206/133b may contribute to the pathogenesis of BC.

PMID- 24935472
TI  - SMAD7: a timer of tumor progression targeting TGF-beta signaling.
AB  - In the context of cancer, transforming growth factor beta (TGF-beta) is a cell
      growth suppressor; however, it is also a critical inducer of invasion and
      metastasis. SMAD is the important mediator of TGF-beta signaling pathway, which
      includes receptor-regulated SMADs (R-SMADs), common-mediator SMADs (co-SMADs),
      and inhibitory SMADs (I-SMADs). I-SMADs block the activation of R-SMADs and co
      SMADs and thus play important roles especially in the SMAD-dependent signaling.
      SMAD7 belongs to the I-SMADs. As an inhibitor of TGF-beta signaling, SMAD7 is
      overexpressed in numerous cancer types and its abundance is positively correlated
      to the malignancy. Emerging evidence has revealed the switch-in-role of SMAD7 in
      cancer, from a TGF-beta inhibiting protein at the early stages that facilitates
      proliferation to an enhancer of invasion at the late stages. This role change may
      be accompanied or elicited by the tumor microenvironment and/or somatic mutation.
      Hence, current knowledge suggests a tumor-favorable timer nature of SMAD7 in
      cancer progression. In this review, we summarized the advances and recent
      findings of SMAD7 and TGF-beta signaling in cancer, followed by specific
      discussion on the possible factors that account for the functional changes of
      SMAD7.

PMID- 24935475
TI  - Structure of Bergman-type W-TiZrNi approximants to quasicrystal, analyzed by
      lattice inversion method.
AB  - The combined interatomic pair potentials of TiZrNi, including Morse and Inversion
      Gaussian, are successfully built by the lattice inversion method. Some
      experimental controversies on atomic occupancies of sites 6-8 in W-TiZrNi are
      analyzed and settled with these inverted potentials. According to the
      characteristics of composition and site preference occupancy of W-TiZrNi, two
      stable structural models of W-TiZrNi are proposed and the possibilities are
      partly confirmed by experimental data. The stabilities of W-TiZrNi mostly result
      from the contribution of Zr atoms to the phonon densities of states in lower
      frequencies. 

PMID- 24935474
TI  - The diagnostic value of serum hybrid capture 2 (CH2) HPV DNA in cervical cancer:
      a systematic review and meta-analysis.
AB  - The diagnostic accuracy of cervical cancer remains a clinical challenge, and a
      number of studies have used the serum hybrid capture 2 (HC2) human papillomavirus
      (HPV) DNA in the diagnosis of cervical cancer. The aim of the present meta
      analysis was to determine the overall accuracy of HC2 HPV DNA in the diagnosis of
      cervical cancer. A systematic review of studies from PubMed, Embase, the Cochrane
      Library, Web of Science, Ovid, Chinese Biomedical Literature Database-disc,
      Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP),
      and Wan Fang database was conducted, and the data concerning the accuracy of HC2
      HPV DNA in the diagnosis of cervical cancer were pooled. The methodological
      quality of each study was assessed by quality assessment for studies of
      diagnostic accuracy (QUADAS). Statistical analysis was performed by employing
      Meta-DiSc (version 1.4) and Stata (version 12.0) software. The overall test
      performance was summarized using receiver operating characteristic curves.
      Finally, 12 studies, including 12,492 subjects, met the inclusion criteria and
      then included in this present meta-analysis. The summary estimates for serum HC2
      HPV DNA in the diagnosis of cervical cancer were as follows: sensitivity 0.83 (95
      % confidence interval (CI) 0.81-0.85), specificity 0.71 (95 % CI 0.69-0.72),
      positive likelihood ratio 3.65 (95 % CI 1.77-7.54), negative likelihood ratio
      0.32 (95 % CI 0.21-0.48), and diagnostic odds ratio 10.54 (95 % CI 4.95-22.46),
      and the area under the curve was 0.8922. Our findings suggest that HC2 HPV DNA
      may improve the accuracy of cervical cancer diagnosis, while the results of HC2
      HPV DNA assays should be interpreted in parallel with conventional test results
      and other clinical findings.

PMID- 24935476
TI  - Exploring the reciprocal modulation of time and space in dancers and non-dancers.
AB  - We explored whether time and space representations modulate each other in
      subjects that are trained to integrate time and space dimensions, i.e.,
      professional dancers. A group of dancers, and one of non-dancers, underwent two
      different tasks employing identical stimuli. A first static central line could
      last one of three possible durations and could have one of three possible
      lengths. A second growing line appeared from the left or right of the screen and
      grew up toward the opposite direction at constant velocity. In the Spatial task,
      subjects encoded the length of the static line and stopped the growing line when
      it had reached half the length of the static one, regardless of time travel. In
      the Temporal task, subjects encoded the duration of the static line and stopped
      the growing line when it had lasted half the duration of the static one,
      regardless of space traveled. Dancers, differently from non-dancers, anticipated
      time in the Temporal task. However, both dancers and non-dancers were biased by
      the stimulus length when performing the Temporal task, while they were not biased
      by the stimulus duration when performing the Spatial task. Concluding, this study
      underlines the plasticity of time dimension that can be influenced by spatial
      information and by sensorimotor training for the synchronization in space and
      time.

PMID- 24935478
TI  - Stratification and partial ascertainment of biomarker value in biomarker-driven
      clinical trials.
AB  - This article examines the role of stratification of treatment assignment with
      regard to biomarker value in clinical trials that accept biomarker-positive and 
      negative patients but have a primary objective of evaluating treatment effect
      separately for the marker-positive subset. It also examines the issue of
      incomplete ascertainment of biomarker value and how this affects inference about
      treatment effect for the biomarker-positive subset of patients. I find that
      stratifying the randomization for the biomarker ensures that all patients will
      have tissue collected but is not necessary for the validity of inference for the
      biomarker-positive subset if there is complete ascertainment. If there is not
      complete ascertainment of biomarker values, it is important to establish that
      ascertainment is independent of treatment assignment. Having a large proportion
      of cases with biomarker ascertainment is not necessary for establishing internal
      validity of the treatment evaluation in biomarker-positive patients; independence
      of ascertainment and treatment is the important factor. Having a large proportion
      of cases with biomarker ascertainment makes it more likely that biomarker
      positive patients with ascertainment are representative of the biomarker-positive
      patients in the clinical trial (with and without ascertainment), but since the
      patients in the clinical trial are a convenience sample of the population of
      patients potentially eligible for the trial, requiring a large proportion of
      cases with ascertainment does not facilitate generalizability of conclusions. 

PMID- 24935477
TI  - Perceptual averaging governs antisaccade endpoint bias.
AB  - Antisaccades entail decoupling the spatial relations between stimulus and
      response and executing a saccade to a target's mirror-symmetrical location. The
      indirect spatial relations require that a relative target percept supports
      antisaccade sensorimotor transformations. Here, we sought to identify whether the
      percept supporting antisaccades results in a respective over- and undershooting
      bias for the near and far targets within a stimulus-set (i.e., oculomotor range
      effect hypothesis) or renders an eccentricity-specific bias based on a
      statistical summary of the individual target percepts in a stimulus-set (i.e.,
      perceptual averaging hypothesis). Antisaccades (and complementary prosaccades)
      were completed in separate blocks (i.e., proximal and distal) that contained an
      equal number of target eccentricities, but differed with respect to their
      magnitudes. The proximal block included eccentricities of 3.0 degrees , 5.5
      degrees , 8.0 degrees , 10.5 degrees , and 13.0 degrees , whereas the distal
      block included eccentricities of 10.5 degrees , 13.0 degrees , 15.5 degrees ,
      18.0 degrees , and 20.5 degrees . The proximal block showed that antisaccade
      amplitudes to the central target (8.0 degrees ) did not elicit a reliable bias,
      whereas the block's 'near' (3.0 degrees  and 5.5 degrees ) and 'far' (10.5
      degrees  and 13.0 degrees ) targets produced an over- and undershooting bias,
      respectively. Notably, however, the distal block showed a reliable-and large
      magnitude-undershooting bias for the central target (i.e., 15.5 degrees ): a bias
      that generalized to each target within the block. Taken together, results for the
      proximal and distal blocks are incompatible with the range effect hypothesis.
      Instead, results indicate that the visual percept supporting antisaccades is
      based on the statistical summary of the range of target eccentricities within a
      stimulus-set (i.e., perceptual averaging). Moreover, perceptual averaging
      represents a parsimonious basis by which the oculomotor system can specify
      sensorimotor transformations via non-veridical (i.e., relative) visual
      information.

PMID- 24935479
TI  - Anti-tuberculosis drugs adverse reactions: a review of the Iranian literature.
AB  - INTRODUCTION: Tuberculosis (TB) treatment, in particular therapy for multidrug
      resistant TB (MDR-TB), is associated with toxicities and adverse drug reactions
      (ADRs). AREAS COVERED: This paper reviews Iranian literature reporting ADRs which
      occurred during tuberculosis treatment. English language papers were sourced from
      PubMed, ScienceDirect, Wiley, Ovid and Proquest, with Google Scholar searched for
      Persian language articles. Reported ADRs, proportion of patients with ADRs, risk
      factors and determinants, as well as the characteristics of the studies were
      reviewed. 21 articles were included; about 60% of them were in English and three
      included patients with MDR-TB. The ratio of ADR per capita was 1.9 (in 6 studies)
      and 33.63% of patients developed an ADR (in 7 studies). Hepatitis (2.5 - 45.3%)
      was reported in nearly all of the studies. The mean time from initiation of
      medication to development of hepatitis ranged from 4.67 to 25.25 days (in 6
      studies). Most cases of mortality were due to hepatotoxicity. Except for
      comorbidities and female gender, other risk factors such as HIV and length of
      hospitalization were only reported in one article. EXPERT OPINION: The pattern of
      ADRs in Iranian articles was found to be similar to many other studies in the
      present review. We suggest that future studies resolve the confounding factors in
      this area that are mentioned in this review.

PMID- 24935480
TI  - Overview and safety of fingolimod hydrochloride use in patients with multiple
      sclerosis.
AB  - INTRODUCTION: Fingolimod (Gilenya(r), FTY720) is an oral sphingosine-1-phosphate
      analogue that was approved by the FDA in 2010 for the treatment of relapsing
      forms of multiple sclerosis (MS). Fingolimod's mechanism of action is primarily
      related to lymphocyte sequestration in primary and secondary lymphoid tissues.
      Phase III trials demonstrated a reduction in annualized relapse rate and MRI
      progression in fingolimod-treated subjects compared with both placebo and IFN
      beta-treated subjects. Frequent adverse effects include fatigue, gastrointestinal
      disturbance, headache and upper respiratory tract infection. More serious, but
      rare, adverse events associated with fingolimod include atrioventricular block,
      symptomatic bradycardia, herpetic viral infections and macular edema. AREAS
      COVERED: We discuss the mechanism of action, pharmacokinetics, clinical efficacy
      and safety profile of fingolimod in patients with relapsing MS. EXPERT OPINION:
      Fingolimod is an effective treatment for relapsing MS and its oral route of
      administration may be preferred by some. Fingolimod is generally well tolerated
      but requires diligence in patient selection and monitoring. Additional
      information is needed regarding risk of infection, malignancy and rebound disease
      with long-term use of fingolimod.

PMID- 24935482
TI  - Effect of remineralizing agents on bond strength of orthodontic brackets: an in
      vitro study.
AB  - BACKGROUND: The purpose of this study is to evaluate the effect of casein
      phosphopeptide amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride
      (CPP-ACP-F) on the shear bond strength (SBS) of orthodontic brackets bonded with
      two different adhesive systems. METHODS: One hundred twenty-six human premolar
      teeth were selected. One hundred twenty teeth were used for SBS testing, and six
      teeth were used for scanning electron microscope (SEM) examination. One hundred
      twenty premolars were divided into mainly three groups: CPP-ACP (group A), CPP
      ACP-F (group B), and control group (group C). Each group was sub-divided into two
      groups according to the bonding adhesive, light cure (groups A1, B1, and C1) and
      chemical cure (groups A2, B2, and C2). The teeth were pre-treated with the group
      specified preventive agent 1 h/day for five consecutive days. Standard edgewise
      brackets were bonded with the respective adhesives. SBS evaluation was done with
      the universal testing machine. After debonding, all the teeth were scored for
      adhesive remaining on the buccal surface, in accordance to adhesive remnant
      index, under a stereomicroscope. The acid-etched enamel surfaces were observed
      under SEM after treatment with CPP-ACP, CPP-ACP-F, and artificial saliva. RESULT:
      In light-cure adhesive group, CPP-ACP-F (B1) showed superior results compared to
      the control group (C1), whereas the CPP-ACP group (A1) showed lower mean SBS than
      the control group (C1). Both these differences were not statistically significant
      (p > 0.05). In chemical-cure adhesive group, control group C2 showed
      significantly superior results (p < 0.05) compared to group A2 and group B2. The
      results of two-way ANOVA showed highly significant difference due to adhesive
      types (p < 0.01), whereas enamel pre-treatment showed non-significant difference
      (p > 0.01). CONCLUSION: The SBS of the orthodontic brackets was non-significantly
      affected when the brackets were cured with light-cure bonding system and treated
      with either CPP-ACP or CPP-ACP-F, whereas with chemical-cure adhesive, decreased
      bond strength was seen, which was within the clinically acceptable limits.

PMID- 24935483
TI  - LGBT people's knowledge of and preparedness to discuss end-of-life care planning
      options.
AB  - Despite the devastating impact of HIV/AIDS, end-of-life care planning among
      lesbian, gay, bisexual and transgender (LGBT) communities is relatively under
      researched, especially in Australia. This paper reports findings of a survey of
      305 LGBT people living in New South Wales, which examined their knowledge of and
      attitudes towards end-of-life care. The focus of this paper is their preparedness
      to discuss with healthcare providers any end-of-life care plans. The results
      highlight that while the majority of respondents were aware of three of the four
      key end-of-life care planning options available in New South Wales--enduring
      powers of attorney, enduring guardians and person responsible (only a minority
      had heard of advance healthcare directives)--a much smaller number of people had
      actually taken up these options. Only a minority of respondents were able to
      identify correctly who had the legal right to make treatment decisions for a
      person who is unconscious following a car accident. A small proportion of people
      had discussed end-of-life care options with general practitioners or another main
      healthcare provider, and only in very few cases were these issues raised by the
      practitioners themselves. Those most likely to not feel comfortable discussing
      these issues with practitioners included younger people, those not fully open
      about their sexuality to family members, and transgender people and others who do
      not define their gender as male or female. The paper highlights the importance of
      education strategies to raise awareness of the end-of-life care planning options
      among LGBT people, as well as strategies for increasing health providers'
      preparedness to discuss these issues with LGBT patients.

PMID- 24935485
TI  - [MedUni Vienna Researcher of the Month, June 2014].

PMID- 24935484
TI  - Parkin-mediated ubiquitination of mutant glucocerebrosidase leads to competition
      with its substrates PARIS and ARTS.
AB  - BACKGROUND: Parkinson's disease (PD) is a movement neurodegenerative disorder
      characterized by death of dopaminergic neurons in the substantia nigra pars
      compacta of the brain that leads to movement impairments including bradykinesia,
      resting tremor, postural instability and rigidity. Mutations in several genes
      have been associated with familial PD, such as parkin, pink, DJ-1, LRKK2 and
      alpha-synuclein. Lately, mutations in the GBA gene were recognized as a major
      cause for the development of PD.Mutations in the GBA gene, which encodes for
      lysosomal beta-glucocerebrosidase (GCase), lead to Gaucher disease (GD), an
      autosomal recessive sphingolipidosis characterized by accumulation of
      glucosylceramide, mainly in monocyte-derived cells. It is a heterogeneous
      disease, with Type 1 patients that do not present any primary neurological signs,
      and Type 2 or Type 3 patients who suffer from a neurological disease. The
      propensity of type 1 GD patients and carriers of GD mutations to develop PD is
      significantly higher than that of the non-GD population.We have shown in the past
      that parkin and mutant GCase, expressed in heterologous systems, interact with
      each other, and that normal but not mutant parkin mediates K48-dependent
      proteasomal degradation of mutant GCase variants. METHODS: We tested possible
      competition between mutant GCase and PARIS or ARTS on the E3 ubiquitin ligase
      parkin, using coimmunoprecipitation assays and quantitative real-time PCR.
      RESULTS: We show that endogenous mutant GCase variants associate with parkin and
      undergo parkin-dependent degradation. Mutant GCase competes with the known parkin
      substrates PARIS and ARTS, whose accumulation leads to apoptosis. Dopaminergic
      cells expressing mutant GCase are more susceptible to apoptotic stimuli than
      dopaminergic cells expressing normal GCase, present increased cleavage of caspase
      3 and caspase 9 levels and undergo cell death. CONCLUSIONS: Our results imply
      that presence of mutant GCase leads to accumulation of parkin substrates like
      PARIS and ARTS, which may cause apoptotic death of cells.

PMID- 24935486
TI  - Spousal violence in sub-Saharan Africa: does household poverty-wealth matter?
AB  - INTRODUCTION: Despite the threat of violence to the health and rights of women
      yet, for many years, there has been a dearth of nationally comparable data on
      domestic violence in sub-Saharan Africa. This paper examines whether women from
      poor households are more likely to experience violence from husband/partner than
      other women who are from middle or rich households. METHOD: Data for the study
      are derived from most recent DHS surveys of ever-married women age 15-49 in
      Cameroun(3,691), Kenya(4,336), Mozambique(5610), Nigeria (16,763), Zambia(3,010)
      and Zimbabwe(5,016) who participated in the questions on Domestic Violence
      Module. Bivariate analysis and Binary Logistic Regression Analysis are used to
      explore the linkage between household poverty-wealth and spousal violence while
      simultaneously controlling for confounding variables. RESULTS: The overall
      prevalence of any form of violence (physical, sexual or emotional) ranges from
      30.5% in Nigeria to 43.4% in Zimbabwe; 45.3% in Kenya; 45.5% in Mozambique; 53.9%
      in Zambia and 57.6% in Cameroun. Both bivariate and multivariate analyses show
      that in two of the six countries -Zambia and Mozambique, experience of violence
      is significantly higher among women from non-poor (rich) households than those
      from other households (poor and middle). For Zimbabwe and Kenya, women from poor
      households are more likely to have ever experienced spousal violence than those
      from non-poor households. In the remaining two countries- Nigeria and Cameroun,
      women from the middle class are more likely to have ever suffered abuse from
      husband/partner than those from the poor and rich households. CONCLUSION: Our
      results thus show that similar measurements of household poverty-wealth have
      produced varying relationships with respect to experience of spousal violence in
      six sub-Saharan African countries. In other words, experience of violence cuts
      across all household poverty-wealth statuses and therefore may not provide enough
      explanations on whether household-poverty necessarily serves to facilitate the
      ending of violence. These results suggest that eliminating violence against women
      in sub-Sahara Africa requires a comprehensive approach rather than addressing
      household poverty-wealth alone.

PMID- 24935487
TI  - Micro and macrorheology at fluid-fluid interfaces.
AB  - Interfacial transport phenomena play an important role in the dynamics of liquid
      interfaces found in emulsions, foams, and membranes. Both macroscopic and
      microscopic measurements of interfacial transport and rheology can be made, the
      former typically relying on the use of at least millimeter-scale probes, and the
      latter exploiting the motion of micrometer-scale probes. Recent publications have
      shown multiple orders of magnitude differences between experimentally observed
      diffusivities in passive microrheology, and the diffusivities expected based on
      macroscopic measurements of the surface rheology. In the present work,
      interfacial rheological measurements were made with both microrheological and
      macrorheological methods and the results are compared for different monolayers at
      an air-water interface. We have identified multiple aspects of particle-tracking
      microrheology that can contribute to orders-of-magnitude disagreement with
      macrorheological methods. In particular, unintentional tracking of particles not
      residing at the interface, the presence of large-scale interfacial
      heterogeneities, and underestimating static noise can all decrease estimates of
      surface viscosity from particle-tracking microrheology by orders of magnitude.
      After taking care to address these artifacts, we show that viscosities obtained
      from both methods agree well for poly(tert-butyl methacrylate) (PtBMA), and for
      dipalmitoylphosphatidylcholine (DPPC), but disagree by orders of magnitude for
      hexadecanol. In poly(tert-butyl acrylate) (PtBA), large-scale heterogeneities
      prevented us from obtaining representative surface viscosities. By making surface
      viscosity measurements in an interfacial stress rheometer (ISR) with needles of
      different aspect ratio, we show that compressibility or Marangoni stress related
      effects may be contributing to the orders of magnitude disagreement in micro and
      macrorheological measurements observed in the hexadecanol system. 

PMID- 24935489
TI  - Stroke prevention in women: synopsis of the 2014 American Heart
      Association/American Stroke Association guideline.
AB  - DESCRIPTION: In February 2014, the American Heart Association/American Stroke
      Association released their first guideline focused on stroke prevention in women.
      This new guideline highlights unique risk factors for stroke in women, including
      oral contraception and hormone therapy, and pregnancy-associated disorders, such
      as preeclampsia, that may have long-lasting consequences on a woman's health. It
      also addresses hypertension; atrial fibrillation; migraine headache with aura;
      and the epidemiology of types of stroke, such as aneurysmal subarachnoid
      hemorrhage and cerebral vein thrombosis, that are predominant in women. METHODS:
      Members of a multidisciplinary expert panel searched, reviewed, and critiqued
      relevant English-language literature published between 1990 and May 2013. The
      panel devised evidence tables and developed recommendations using American Heart
      Association guideline procedures and levels of evidence. RECOMMENDATIONS: This
      synopsis of the guideline summarizes the evidence about risk factors for stroke
      in women and suggests prevention strategies. It also describes the new
      recommendations relevant to identifying and treating hypertensive disorders in
      pregnancy that increase risk for stroke.

PMID- 24935492
TI  - My audition.

PMID- 24935491
TI  - Statins, primary prevention, and overall mortality.

PMID- 24935493
TI  - Etymology.

PMID- 24935494
TI  - Guns, suicide, and homicide.

PMID- 24935495
TI  - Guns, suicide, and homicide.

PMID- 24935496
TI  - Guns, suicide, and homicide--in response.

PMID- 24935497
TI  - Futility: another way?

PMID- 24935498
TI  - Futility: another way?

PMID- 24935499
TI  - Futility: another way?

PMID- 24935500
TI  - Futility: another way?

PMID- 24935501
TI  - Futility: another way?--in response.

PMID- 24935503
TI  - Web Exclusives. The consult guys - a trip to the hardware store: is an MRI safe?

PMID- 24935504
TI  - ACP Journal Club. Radical prostatectomy reduced long-term mortality more than
      watchful waiting in early prostate cancer.

PMID- 24935505
TI  - ACP Journal Club. In pregnant smokers, the nicotine patch did not increase
      abstinence or birthweight more than placebo.

PMID- 24935506
TI  - ACP Journal Club. Red blood cell transfusion after PCI was associated with
      increased mortality, MI, and stroke.

PMID- 24935507
TI  - ACP Journal Club. In treatment-resistant depression, adding cognitive-behavioral
      therapy to usual care was cost-effective at 1 y.

PMID- 24935508
TI  - ACP Journal Club. In patients at high CV risk, a Mediterranean diet plus olive
      oil reduced diabetes more than advising a low-fat diet.

PMID- 24935509
TI  - ACP Journal Club. Review: vegetarian diets reduce systolic and diastolic blood
      pressure more than omnivorous diets.

PMID- 24935510
TI  - ACP Journal Club. In overweight or obese patients with diabetes, a lifestyle
      intervention increased weight loss at 8 years.

PMID- 24935511
TI  - ACP Journal Club. Review: primary care-based general health checks improve
      surrogate but not clinical outcomes.

PMID- 24935512
TI  - ACP Journal Club. Probiotics did not prevent antibiotic-associated or C.
      difficile diarrhea in hospitalized older patients.

PMID- 24935513
TI  - ACP Journal Club. In AF, apixaban reduced stroke or systemic embolism compared
      with warfarin, regardless of patient age.

PMID- 24935514
TI  - ACP Journal Club. Review: noninvasive vs invasive weaning from mechanical
      ventilation reduces mortality in respiratory failure.

PMID- 24935515
TI  - ACP Journal Club. In septic shock, early goal-directed or standard protocol-based
      therapy did not reduce mortality.

PMID- 24935516
TI  - Cognitive function in chronic obstructive pulmonary disease: relationship to
      global initiative for chronic obstructive lung disease 2011 categories.
AB  - BACKGROUND AND OBJECTIVE: Recently, comorbidities such as impaired cognitive
      function have been attracting more focus when considering the management of
      chronic obstructive pulmonary disease (COPD). Here we investigated the
      relationship between cognitive function and the categories given in the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011.
      Specifically, after controlling for non-COPD covariates, we assessed the clinical
      features that may be predictive of cognitive impairment in patients with COPD.
      METHODS: We recruited 119 stable patients with mild to very severe COPD. We
      administered a broad array of standardized neuropsychological tests that assessed
      cognitive functions in the domains of attention, memory, psychomotor coordination
      and language. RESULTS: Cognitive scores were significantly different between
      patients falling within GOLD 2011 categories. Scores were lower in patients with
      high future risk compared with low future risk. In parallel, there were
      significant differences in cognitive function between COPD patient subgroups when
      patients were grouped according to the forced expiratory volume in 1 s,
      exacerbation history and C-reactive protein levels. After controlling for non
      COPD predictors, only exacerbation history remained a significant predictor of
      cognitive scores. CONCLUSIONS: The number of exacerbation events in a year may be
      used as a predictor of cognitive impairment in patients with COPD.

PMID- 24935518
TI  - Subcutaneous seeding of 'double hit' diffuse large B-cell lymphoma from staging
      bone marrow biopsy.

PMID- 24935519
TI  - Energy-transfer from ultra-small Au nanoclusters to Er3+ ions: a short-range
      mechanism.
AB  - Sub-nanometric Au nanoclusters are known to act as very efficient sensitizers for
      the luminescent emission of Er(3+) ions in silica through a non-resonant broad
      band energy-transfer mechanism. In the present work the energy-transfer process
      is investigated in detail by room temperature photoluminescence characterization
      of Er and Au co-implanted silica systems in which a different degree of coupling
      between Er(3+) ions and Au nanoclusters is obtained. The results allow us to
      definitely demonstrate the short-range nature of the interaction in agreement
      with non-radiative energy-transfer mechanisms. Moreover, an upper limit to the
      interaction length is also set by the Au-Au intercluster semi-distance which is
      smaller than 2.4 nm in the present case. 

PMID- 24935517
TI  - Midazolam and propofol used alone or sequentially for long-term sedation in
      critically ill, mechanically ventilated patients: a prospective, randomized
      study.
AB  - INTRODUCTION: Midazolam and propofol used alone for long-term sedation are
      associated with adverse effects. Sequential use may reduce the adverse effects,
      and lead to faster recovery, earlier extubation and lower costs. This study
      evaluates the effects, safety, and cost of midazolam, propofol, and their
      sequential use for long-term sedation in critically ill mechanically ventilated
      patients. METHODS: A total of 135 patients who required mechanical ventilation
      for >3 days were randomly assigned to receive midazolam (group M), propofol
      (group P), or sequential use of both (group M-P). In group M-P, midazolam was
      switched to propofol until the patients passed the spontaneous breathing trial
      (SBT) safety screen. The primary endpoints included recovery time, extubation
      time and mechanical ventilation time. The secondary endpoints were pharmaceutical
      cost, total cost of ICU stay, and recollection to mechanical ventilation-related
      events. RESULTS: The incidence of agitation following cessation of sedation in
      group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean
      percentage of adequate sedation and duration of sedation were similar in the
      three groups. The recovery time, extubation time and mechanical ventilation time
      of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5)
      hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly
      longer than the other groups, while they were similar between the other two
      groups. In the treatment-received analysis, ICU duration was longer in group M
      than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment
      received analysis, respectively, the pharmaceutical cost of group M-P was lower
      than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P =
      0.015). The proportion of group M-P with unbearable memory of the uncomfortable
      events was lower than in group M (11.7% versus 25.0%, P <0.01), while the
      proportion with no memory was similar (P >0.05). The incidence of hypotension in
      group M-P was lower than group (P = 0.01). CONCLUSION: Sequential use of
      midazolam and propofol was a safe and effective sedation protocol, with higher
      clinical effectiveness and better cost-benefit ratio than midazolam or propofol
      used alone, for long-term sedation of critically ill mechanically ventilated
      patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01173443.
      Registered 25 February 2014.

PMID- 24935520
TI  - Crucial factor for increasing the conjugation frequency in Streptomyces netropsis
      SD-07 and other strains.
AB  - Streptomyces netropsis SD-07, the producer of novel polyene macrolide antifungal
      antibiotics, was isolated from soil. For the investigation of the functions of
      its biosynthesis genes and regulation mechanisms, a genetic operating system is
      necessary. In this study, we successfully transferred the plasmid DNA of pSET152
      from the methylation deficient donor, Escherichia coli ET12567/pSET152/pUZ8002,
      to S. netropsis SD-07 by conjugation and evaluated the crucial factors
      influencing the conjugation frequency. Ca(2+) ions in presence the conjugation
      media may increase the conjugation frequency by 1000-10 000 times than Ca(2+)
      ions absence in the same conjugation media, and 10-100 time higher than Mg(2+)
      ions. Similar results (increasing the conjugation frequency by 10-100 times when
      media containing 60 mM CaCl2 ) were also obtained from the conjugation between E.
      coli ET12567 and Streptomyces coelicolor, S. lavendulae, S. venezuelae, despite
      their conjugation media were different (MS, CM, GS). So, CaCl2 concentration is a
      crucial factor for increasing the conjugation frequency, and the suitable
      concentration may probably be 60 mM. In addition, synthetic medium containing a
      small amount of organic nitrogen source may benefit increasing the conjugation
      frequency. These findings could be valuable for the development of a practical
      method for achieving conjugation in other Streptomyces spp.

PMID- 24935521
TI  - Advancing the application of systems thinking in health: realist evaluation of
      the Leadership Development Programme for district manager decision-making in
      Ghana.
AB  - BACKGROUND: Although there is widespread agreement that strong district manager
      decision-making improves health systems, understanding about how the design and
      implementation of capacity-strengthening interventions work is limited. The Ghana
      Health Service has adopted the Leadership Development Programme (LDP) as one
      intervention to support the development of management and leadership within
      district teams. This paper seeks to address how and why the LDP 'works' when it
      is introduced into a district health system in Ghana, and whether or not it
      supports systems thinking in district teams. METHODS: We undertook a realist
      evaluation to investigate the outcomes, contexts, and mechanisms of the
      intervention. Building on two working hypotheses developed from our earlier work,
      we developed an explanatory case study of one rural district in the Greater Accra
      Region of Ghana. Data collection included participant observation, document
      review, and semi-structured interviews with district managers prior to, during,
      and after the intervention. Working backwards from an in-depth analysis of the
      context and observed short- and medium-term outcomes, we drew a causal loop
      diagram to explain interactions between contexts, outcomes, and mechanisms.
      RESULTS: The LDP was a valuable experience for district managers and teams were
      able to attain short-term outcomes because the novel approach supported teamwork,
      initiative-building, and improved prioritisation. However, the LDP was not
      institutionalised in district teams and did not lead to increased systems
      thinking. This was related to the context of high uncertainty within the
      district, and hierarchical authority of the system, which triggered the LDP's
      underlying goal of organisational control. CONCLUSIONS: Consideration of
      organisational context is important when trying to sustain complex interventions,
      as it seems to influence the gap between short- and medium-term outcomes. More
      explicit focus on systems thinking principles that enable district managers to
      better cope with their contexts may strengthen the institutionalisation of the
      LDP in the future.

PMID- 24935522
TI  - Modeling of photocurrent kinetics upon pulsed photoexcitation of photosynthetic
      proteins: a case of bacteriorhodopsin.
AB  - The proton pump of bacteriorhodopsin in an aqueous solution at varied pH upon
      pulsed excitation was monitored using a solution-based electrochemical module.
      The photocurrent action spectrum agreed with the absorption contour at 495-645
      nm. Diminishing the photocurrent amplitude by adding a protonophore, carbonyl
      cyanide m-chlorophenyl hydrazone, revealed that protons were the charge carriers
      of the photocurrent. The evolution of the conventional proton pump is proposed to
      occur in three elementary steps consecutively: first, the proton relay from the
      protonated Schiff base to the purple membrane (PM) surface (k1), then the proton
      exchange between PM surface and bulk (k2), and finally, the proton uptake (k3).
      The fitted temporal profiles of the photocurrent agreed with observations in the
      pH range 5.8-9.5. At pH 7.3, k1, k2, and k3 were 2098 s(-1), 412 s(-1), and 44 s(
      1), respectively. The rate coefficients at pH 9.5 were smaller than those at pH
      6.3 by a factor of approximately 2, consistent with the differences in the
      intrinsic mobilities of the charge carriers proton and hydroxide ion. The
      combination of the electrochemical detection module and the concomitant model
      provides a promising tool for quantitative and qualitative characterization of
      the light-driven ion pumps.

PMID- 24935524
TI  - Identifying the ichthyoplankton of a coral reef using DNA barcodes.
AB  - Marine fishes exhibit spectacular phenotypic changes during their ontogeny, and
      the identification of their early stages is challenging due to the paucity of
      diagnostic morphological characters at the species level. Meanwhile, the
      importance of early life stages in dispersal and connectivity has recently
      experienced an increasing interest in conservation programmes for coral reef
      fishes. This study aims at assessing the effectiveness of DNA barcoding for the
      automated identification of coral reef fish larvae through large-scale
      ecosystemic sampling. Fish larvae were mainly collected using bongo nets and
      light traps around Moorea between September 2008 and August 2010 in 10 sites
      distributed in open waters. Fish larvae ranged from 2 to 100 mm of total length,
      with the most abundant individuals being <5 mm. Among the 505 individuals DNA
      barcoded, 373 larvae (i.e. 75%) were identified to the species level. A total of
      106 species were detected, among which 11 corresponded to pelagic and
      bathypelagic species, while 95 corresponded to species observed at the adult
      stage on neighbouring reefs. This study highlights the benefits and pitfalls of
      using standardized molecular systems for species identification and illustrates
      the new possibilities enabled by DNA barcoding for future work on coral reef fish
      larval ecology.

PMID- 24935526
TI  - Exploratory analysis of the relationship between home health agency engagement in
      a national campaign and reduction in acute care hospitalization in US home care
      patients.
AB  - RATIONALE, AIMS AND OBJECTIVES: To determine whether US home health agencies that
      intensively engaged with the 2010 Home Health Quality Improvement National
      Campaign were more likely to reduce acute care hospitalization (ACH) rates than
      less engaged agencies. METHOD: We included all Medicare-certified agencies that
      accessed Campaign resources in the first month of the Campaign and also responded
      to an online survey of resource utilization at month two. We used the survey data
      and item response theory to estimate a latent construct we called engagement with
      the campaign. ACH rates were calculated from the Centers for Medicare & Medicaid
      Services Outcome and Assessment Information Set for pre- and post-intervention
      periods (March-November 2009 and 2010, respectively). RESULTS: Staff from 1077
      agencies accessed resources in the first month of the Campaign. Of these, 382
      provided information about resource use and had 10 or more monthly discharges
      throughout the measurement periods. Dividing these agencies into quartiles based
      on engagement score, we found an association between engagement and reduction in
      ACH rates, P=0.049 (chi(2) for trend). Exploratory path analysis revealed the
      effect of engagement score on reduction in ACH rate to be partially mediated
      through reduction in average length of service rates. CONCLUSION: We found
      evidence that early intensity of engagement with the Campaign, as measured
      through use of activities and resources, was positively associated with
      improvement. To continue the investigation of this relationship, future work in
      this and other campaigns should focus on further development of engagement
      measures.

PMID- 24935527
TI  - First reported case of interferon-alpha-induced sarcoidosis in an Asian patient
      with malignant melanoma.
AB  - Anticancer agents can induce sarcoidosis. Interferon-alpha, which is used for the
      treatment of malignant melanoma and renal cell cancer, is one causative agent of
      sarcoidosis. However, there are few reports of interferon-alpha-induced
      sarcoidosis in patients with malignant melanoma. Clinically, it is important to
      consider the possibility of sarcoidosis in such patients because it could be
      easily regarded as a metastatic lesion due to underlying malignancy and given
      unnecessary treatment. Here, we report on the first case of interferon-alpha
      induced sarcoidosis in an Asian melanoma patient.

PMID- 24935523
TI  - Molecular biomarkers in interstitial lung diseases.
AB  - Interstitial lung diseases (ILD) are protean conditions with substantial overlap
      in terms of diagnosis, prognostic evaluation, and management. However, the
      management of idiopathic pulmonary fibrosis is different from that of more
      immunologically driven ILD patterns, such as ILD associated with connective
      tissue diseases. It is important to provide accurate diagnosis and patient
      selection for prognostication and timely treatment, preferably at baseline.
      Validated non-invasive biomarkers fulfilling these unmet clinical needs are
      warranted. Although no ILD biomarker has been adopted in clinical practice so
      far, advancements in this field have been achieved, especially with the
      implementation of high-throughput techniques and clinical-laboratory multi
      parametric panels. This review focuses on selected validated and/or potentially
      interesting biomarkers investigated in the peripheral blood and lung tissue of
      patients with ILD. Current issues and future directions in various aspects of ILD
      biomarkers research and its clinical application are explored. 

PMID- 24935525
TI  - In vitro and in vivo studies of BMP-2-loaded PCL-gelatin-BCP electrospun
      scaffolds.
AB  - To confirm the effect of recombinant human bone morphogenetic protein-2 (BMP-2)
      for bone regeneration, BMP-2-loaded polycaprolactone (PCL)-gelatin (Gel)-biphasic
      calcium phosphate (BCP) fibrous scaffolds were fabricated using the
      electrospinning method. The electrospinning process to incorporate BCP
      nanoparticles into the PCL-Gel scaffolds yielded an extracellular matrix-like
      microstructure that was a hybrid system composed of nano- and micro-sized fibers.
      BMP-2 was homogeneously loaded on the PCL-Gel-BCP scaffolds for enhanced
      induction of bone growth. BMP-2 was initially released at high levels, and then
      showed sustained release behavior for 31 days. Compared with the PCL-Gel-BCP
      scaffold, the BMP-2-loaded PCL-Gel-BCP scaffold showed improved cell
      proliferation and cell adhesion behavior. Both scaffold types were implanted in
      rat skull defects for 4 and 8 weeks to evaluate the biological response under
      physiological conditions. Remarkable bone regeneration was observed in the BMP
      2/PCL-Gel-BCP group. These results suggest that BMP-2-loaded PCL-Gel-BCP
      scaffolds should be considered for potential bone tissue engineering
      applications. 

PMID- 24935528
TI  - Performance of compulsive behavior in rats is not a unitary phenomenon -
      validation of separate functional components in compulsive checking behavior.
AB  - A previous analysis of the quinpirole sensitisation rat model of obsessive
      compulsive disorder revealed that the behavioral phenotype of compulsive checking
      consists of three constitutive components - vigor of checking performance, focus
      on the task of checking, and satiety following a bout of checking. As
      confirmation of this analysis, the aim of the present study was to reconstitute,
      without quinpirole treatment, each of the putative components, with the
      expectation that these would self-assemble into compulsive checking. To
      reconstitute vigor and satiety, the employed treatment was a bilateral lesion of
      the nucleus accumbens core (NAc), as this treatment was shown previously to
      exaggerate these components. To reconstitute focus, the employed treatment was a
      low dose of the serotonin-1A receptor agonist 8-hydroxy-2-(di-n-propylamino)
      tetralin hydrochloride (DPAT) (0.0625 mg/kg), as high doses of this drug induce
      compulsive behavior and exacerbate focus. Results showed that injection of DPAT
      to NAc lesion rats did yield compulsive checking. Neither the drug alone nor the
      NAc lesion by itself produced compulsive checking. The demonstrated synthesis of
      compulsive checking by the combined treatment of low-dose DPAT and NAc lesion
      strengthened the previous fractionation of the model obsessive-compulsive
      disorder phenotype into three constitutive components, and suggested a role for
      serotonin-1A receptors outside the NAc in enhanced focus on the task of checking.

PMID- 24935529
TI  - Is minor salivary gland biopsy more than a diagnostic tool in primary Sjogren's
      syndrome? Association between clinical, histopathological, and molecular
      features: a retrospective study.
AB  - OBJECTIVES: Several histological scoring systems, including the focus score,
      performed in minor salivary glands (MSGs) by hematoxylin-eosin (H&E) staining,
      have been employed in clinical practice to assess the inflammatory infiltrate and
      provide the diagnosis of primary Sjogren's syndrome (pSS). Aims of this study
      were to integrate different scoring systems and identify potential differences in
      the molecular profile of lymphoid cytokines related to germinal center (GC)
      formation and clinical subsets in pSS. METHODS: Overall, 104 pSS patients and 40
      subjects with sicca non-pSS were retrospectively evaluated. MSG biopsies were
      evaluated by H&E and immunofluorescence to assess histological pattern, Chisholm
      and Mason grading system, Tarpley score, a grading for the severity of
      inflammatory infiltrate, T-/B-cell segregation, and the presence of GC. MSGs from
      50 pSS patients and 30 sicca non-pSS patients were processed by real-time PCR to
      assess LTalpha, LTbeta, BAFF, CXCR4, CXCL12, CXCR5, CXCL13, CCR7, CCL19, and
      CCL21. RESULTS: GCs presence was associated with anti-Ro/SSA and anti-La/SSB
      antibodies, hypergammaglobulinemia, salivary gland swelling, higher Tarpley score
      and focus score, and extraglandular involvement but, at multivariate analysis,
      only extraglandular involvement was independently associated to GC. pSS patients
      displayed higher level of all cytokines compared to those with sicca symptoms.
      GC(+) pSS patients displayed higher level of all cytokines compared to those GC(
      ). CONCLUSIONS: Our study demonstrates that different histopathological patterns,
      including GC presence, reflect different cytokine expression and different
      clinical subsets. We believe that the combined immunofluorescence/molecular
      approach in MSGs would help to tailor diagnostic and therapeutic approach for
      different subsets of pSS patients.

PMID- 24935530
TI  - Abdominal aortitis in HLA-B27+ spondyloarthritis: case report with 5-year follow
      up and literature review.
AB  - OBJECTIVES: Aortic disease is a known complication of HLA-B27-associated
      spondyloarthritis. We present the case of a 52-year-old HLA-B27-positive woman
      with aortitis of the abdominal aorta and spondyloarthritis. METHODS: In addition
      to the case reported, a literature search (MEDLINE) for articles published
      between 1946 and September 2013 was performed using combinations of the MEDLINE
      subject headings keywords "spondylarthritis," "ankylosing spondylitis," "reactive
      arthritis," "psoriatic arthritis," "aortitis," and "abdominal aorta." Relevant
      references were retrieved. RESULTS:  CASE REPORT: Our patient presented to the ER
      in June 2008 with a 3-week history of worsening of severe cramping lower
      abdominal pain. Her history also included recurrent acute episodes of iritis,
      which eventually led to enucleation of her left eye despite treatment with
      corticosteroids. CT of the abdomen showed findings suggesting aortitis of the
      abdominal aorta. She responded to therapy with prednisone, and follow-up imaging
      showed eventual resolution of the aortitis. She later went on to be diagnosed
      with psoriatic arthritis with spondylitis. REVIEW OF LITERATURE: Six previously
      reported cases of abdominal aortitis in spondyloarthritis were found. Four of
      these were reported in patients with ankylosing spondylitis, one in reactive
      arthritis, and one in psoriatic arthritis. The first case reported was in 1958
      and the most recent in 2012. CONCLUSIONS: Rheumatologists should be aware of the
      possibility of abdominal aortitis occurring in their patients with SpA and should
      consider it as part of the differential diagnosis in a SpA patient with
      unexplained visceral pain or systemic features out of proportion to clinically
      apparent disease.

PMID- 24935531
TI  - The effect of photodynamic therapy in root canal disinfection: a systematic
      review.
AB  - INTRODUCTION: Effective root canal disinfection is a fundamental component of
      successful root canal treatment. Photodynamic therapy (PDT) has been proposed as
      a new adjunctive method for additional disinfection of the root canal system with
      the possibility of improved treatment outcomes. The aim of this systematic review
      was to investigate the effect of PDT on bacterial load reduction during root
      canal disinfection. METHODS: Two reviewers independently conducted a
      comprehensive literature search using a combination of medical subject heading
      terms and key words to identify studies relevant to the Population Intervention
      Control Outcome question. The selection of articles for inclusion was performed
      in 2 phases based on predetermined eligibility criteria according to Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      Inter-reviewer agreement for each phase was recorded. The effect of PDT on
      bacterial load reduction during root canal disinfection was evaluated as the
      primary outcome variable during data extraction. RESULTS: The literature search
      provided 57 titles and abstracts. Three articles met the inclusion criteria and
      were selected for this systematic review. The reasons for study exclusion in each
      phase were recorded. Because of the heterogeneity in clinical indications and PDT
      protocols among the included studies, a meta-analysis could not be performed. All
      included studies showed a positive effect of PDT in the reduction of microbial
      load in root canal treatment ranging from 91.3%-100%. CONCLUSIONS: Limited
      clinical information is currently available on the use of PDT in root canal
      disinfection. If supported by future clinical research, PDT may have efficacy for
      additional root canal disinfection, especially in the presence of multi-drug
      resistant bacteria.

PMID- 24935532
TI  - Microbial diversity in persistent root canal infections investigated by
      checkerboard DNA-DNA hybridization.
AB  - INTRODUCTION: The aim of the present study was to investigate the composition of
      the root canal microbiota in endodontic failures in order to identify and
      quantify these microorganisms. METHODS: Microbiological samples were taken from
      36 root canals with persistent endodontic infection. The presence, levels, and
      proportions of 79 bacterial species were determined by checkerboard DNA-DNA
      hybridization. The Pearson correlation coefficient was used to investigate the
      relations between bacterial counts and clinical conditions (P <= .05). RESULTS:
      Enterococcus faecium (36%), Streptococcus epidermidis (36%), Eubacterium
      saburreum (28%), Parvimonas micra (28%), Streptococcus sanguis (28%),
      Capnocytophaga sputigena (28%), Leptotrichia buccalis (28%), Enterococcus
      faecalis (28%), and Staphylococcus warneri (28%) were the most prevalent species;
      and there was a low prevalence of Treponema socranskii (3%), Fusobacterium
      periodonticum (3%), Capnocytophaga gingivalis (3%), and Spiroplasma ixodetis
      (3%). The highest mean levels were found for the following species: E. faecium,
      Dialister pneumosintes, Staphylococcus epidermidis and Helicobacter pylori. There
      was a statistically significant difference between the levels of gram-negative
      species and gram-positive species (13.5 * 10(5) vs 6.5 * 10(5), respectively). A
      positive correlation was found between the area of the periapical lesion and the
      levels of gram-negative and rod species (P < .05). CONCLUSIONS: The microbiota
      from teeth with persistent apical periodontitis presents a mixed and complex
      profile, hosting E. faecium and S. epidermidis as the most highly prevalent
      species. No correlation was found between any of the species tested and clinical
      findings; however, periapical lesions with the largest areas presented higher
      counts of gram-negative and rod species.

PMID- 24935533
TI  - An ex vivo comparison of pressures within dental pulp space using conventional
      anesthetic technique versus needle-mounted obturator.
AB  - INTRODUCTION: The intrapulpal (IP) injection technique is 1 of several ways of
      obtaining profound anesthesia. There is evidence to suggest that pressure is the
      primary factor in obtaining anesthesia using IP injection. This is an ex vivo
      comparison of pressures within dental pulp space using the conventional
      anesthetic technique versus a needle-mounted obturator technique. METHODS: Twenty
      extracted anterior and premolar teeth were accessed with a high-speed 169L bur. A
      saline-filled tube connected to a digital pressure gauge was attached to the
      apical 10 mm of each tooth in a fixed mount. One operator performed all the
      injections under moderate pressure. Each tooth was injected twice; first, the
      tooth was given an IP injection with a normal setup, and then the same tooth was
      given an IP injection with the modified obturator syringe. The pressure at the
      apex was recorded for each tooth. A paired sample t test was completed to
      determine statistical significance. RESULTS: The pressure generated was
      considerably higher for the obturator group in every tooth when compared with the
      normal group (P < .001). CONCLUSIONS: IP injection with the obturator resulted in
      increased pressure at the apex of each tooth. This pressure increase may allow
      for increased anesthesia when IP injections are indicated.

PMID- 24935534
TI  - Comparison of endodontic diagnosis and treatment planning decisions using cone
      beam volumetric tomography versus periapical radiography.
AB  - INTRODUCTION: Accurate and confident treatment planning is an essential part of
      endodontic practice. Periapical radiographs have been used to aid in the
      diagnosis of pathology and to help establish an appropriate treatment strategy.
      Recently, a new imaging modality, cone-beam volumetric tomographic (CBVT)
      imaging, has been shown to be a useful tool in a number of endodontic
      applications. The aim of this study was to compare the relative value of
      preoperative periapical radiographs and CBVT scanning in the decision-making
      process in endodontic treatment planning. METHODS: Thirty endodontic cases
      completed in a private endodontic practice were randomly selected to be included
      in this study. Each case was required to have a preoperative digital periapical
      radiograph and a CBVT scan. Three board-certified endodontists reviewed the 30
      preoperative periapical radiographs. Two weeks later, the CBVT volumes were
      reviewed in random order by the same evaluators. The evaluators were asked to
      select a preliminary diagnosis and treatment plan based solely on their
      interpretation of the periapical and CBVT images. Diagnosis and treatment
      planning choices were then compared to determine if there was a change from the
      periapical radiograph to the CBVT scan. RESULTS: A difference in treatment plan
      between the 2 imaging modalities was recorded in 19 of 30 cases (63.3%, P =
      .001), 17 of 30 cases (56.6%, P = .012), and 20 of 30 cases (66.7%, P = .008) for
      examiners 1, 2, and 3, respectively. CONCLUSIONS: Under the conditions of this
      study, preoperative CBVT imaging provides additional information when compared
      with preoperative periapical radiographs, which may lead to treatment plan
      modifications in approximately 62% of the cases.

PMID- 24935535
TI  - Analysis of C-shaped canals by panoramic radiography and cone-beam computed
      tomography: root-type specificity by longitudinal distribution.
AB  - INTRODUCTION: The purpose of this study was to document the characteristics of C
      shaped canal systems in permanent mandibular second molars using a combination of
      orthopantomogram (OPT) and cross-sectional cone-beam computed tomographic (CBCT)
      imaging. METHODS: Two hundred participants (94 men and 106 women, mean age = 35
      years) who underwent both routine CBCT and OPT examinations were enrolled. One
      endodontist and 1 oral radiologist examined the images of 339 mandibular second
      molars and described the radiographic features of C-shaped canals from OPT images
      as confirmed by CBCT imaging. Root morphology was classified as nonfused (NFRI
      II) or fused (FRI-III) based on OPT images. Cross-sectional root canal
      configurations (C1-C5) were identified from CBCT imaging at 3 different levels
      (coronal, middle, and apical). Frequency distributions of root morphology and
      root canal configurations were compared at each level, and interobserver
      reliability was tested using the Cohen kappa test. RESULTS: Of the 339 teeth, 29
      (8.6 %) had C-shaped root canal systems. Most of the root canals were NFR type
      (86%); only 2% had C-shaped root canals (all NFRII). In the FR category, 23 teeth
      with C-shaped canals were equally distributed between the FRI and FRII subtypes.
      Interobserver agreement was almost perfect (kappa = 0.89 and kappa = 0.91; right
      and left second molars, respectively). Per CBCT imaging, the most common
      configuration was C3 at all levels; no C5 case was detected. CONCLUSIONS: OPT
      usage can assist in recognizing and diagnosing C-shaped root canal systems.
      Radicular fusion or proximity is a characteristic feature of C-shaped canal
      systems. However, nonfused root appearances should also be considered suspicious.

PMID- 24935536
TI  - Assessment of the separation incidence of reciprocating WaveOne files: a
      prospective clinical study.
AB  - INTRODUCTION: Despite metallurgical advancements in the nickel-titanium file
      manufacturing process, file separation remains a concern. The purpose of this
      prospective clinical study was to assess the separation incidence of the
      reciprocating WaveOne file (Dentsply Tulsa Dental Specialties, Tulsa, OK) when
      used to prepare root canals of posterior teeth. METHODS: File separation
      incidence was assessed over an 18-month period in which 4 experienced and
      calibrated endodontists performed conventional endodontic treatment on posterior
      teeth using the WaveOne file system. The separation incidence was determined
      based on both the number of teeth and the number of canals instrumented during
      this time period. RESULTS: A total of 2,215 canals (711 teeth) were treated.
      Three instruments (two 21.06 and one 25.08) separated during use and were deemed
      to be irretrievable. The overall instrument separation incidence in relation to
      the number of canals shaped was found to be 0.13% (0.42% teeth). CONCLUSIONS:
      Based on the results of this study, the incidence of endodontic instrument
      separation when using the WaveOne reciprocating file was considerably low.

PMID- 24935537
TI  - Iloprost up-regulates vascular endothelial growth factor expression in human
      dental pulp cells in vitro and enhances pulpal blood flow in vivo.
AB  - INTRODUCTION: Prostacyclin (PGI2) is a biomolecule capable of enhancing
      angiogenesis and cellular proliferation. METHODS: We investigated the influence
      of a PGI2 analogue (iloprost) on dental pulp revascularization in vitro and in
      vivo by using human dental pulp cells (HDPCs) and a rat tooth injury model,
      respectively. Iloprost stimulated the human dental pulp cell mRNA expression of
      vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2),
      and platelet-derived growth factor (PDGF) in a significant dose-dependent manner.
      This mRNA up-regulation was significantly inhibited by pretreatment with a PGI2
      receptor antagonist and forskolin (a protein kinase A activator). In contrast, a
      protein kinase A inhibitor significantly enhanced the iloprost-induced mRNA
      expression of VEGF, FGF-2, and PDGF. Pretreatment with a fibroblast growth factor
      receptor inhibitor attenuated the VEGF, FGF-2, and PDGF mRNA expression,
      indicating opposing regulatory mechanisms. RESULTS: The effect of iloprost on the
      dental pulp was investigated in vivo by using a rat molar pulp injury model. The
      iloprost-treated group exhibited a significant increase in pulpal blood flow at
      72 hours compared with control. CONCLUSIONS: The present study indicates that
      iloprost may be a candidate agent to promote neovascularization in dental pulp
      tissue, suggesting the potential clinical use of iloprost in vital pulp therapy.

PMID- 24935538
TI  - White mineral trioxide aggregate induces migration and proliferation of stem
      cells from the apical papilla.
AB  - INTRODUCTION: Regenerative endodontic protocols recommend white mineral trioxide
      aggregate (WMTA) as a capping material because of its osteoinductive properties.
      Stem cells from the apical papilla (SCAP) are presumed to be involved in this
      regenerative process, but the effects of WMTA on SCAP are largely unknown. Our
      hypothesis was that WMTA induces proliferation and migration of SCAP. METHODS:
      Here we used an unsorted population of SCAP (passages 3-5) characterized by high
      CD24, CD146, and Stro-1 expression. The effect of WMTA on SCAP migration was
      assessed by using transwells, and its effect on proliferation was determined by
      the WST-1 assay. Fetal bovine serum (FBS) and calcium chloride-enriched medium
      were used as positive controls. RESULTS: The SCAP analyzed here showed a low
      percentage of STRO-1+ and CD24+ cells. Both set and unset WMTA significantly
      increased the short-term migration of SCAP after 6 hours (P < .05), whereas
      calcium chloride-enriched medium did after 24 hours of exposure. Set WMTA
      significantly increased proliferation on days 1-5, whereas calcium-enriched
      medium showed a significant increase on day 7, with a significant reduction on
      proliferation afterwards. SCAP migration and proliferation were significantly and
      steadily induced by the presence of 2% and 10% FBS. CONCLUSIONS: Collectively,
      these data demonstrate that WMTA induced an early short-term migration and
      proliferation of a mixed population of stem cells from apical papilla as compared
      with a later and longer-term induction by calcium chloride or FBS.

PMID- 24935539
TI  - Biodentine induces human dental pulp stem cell differentiation through mitogen
      activated protein kinase and calcium-/calmodulin-dependent protein kinase II
      pathways.
AB  - INTRODUCTION: Biodentine (Septodont, Saint-Maur-des-Fosses, France), a new
      tricalcium silicate cement formulation, has been introduced as a bioactive
      dentine substitute to be used in direct contact with pulp tissue. The aim of this
      study was to investigate the response of human dental pulp stem cells (hDPSCs) to
      the material and whether mitogen-activated protein kinase (MAPK), nuclear factor
      kappa B (NF-kappaB), and calcium-/calmodulin-dependent protein kinase II (CaMKII)
      signal pathways played a regulatory role in Biodentine-induced odontoblast
      differentiation. METHODS: hDPCs obtained from impacted third molars were
      incubated with Biodentine. Odontoblastic differentiation was evaluated by
      alkaline phosphatase activity, alizarin red staining, and quantitative real-time
      reverse-transcriptase polymerase chain reaction for the analysis of messenger RNA
      expression of the following differentiation gene markers: osteocalcin (OCN),
      dentin sialophosprotein (DSPP), dentin matrix protein 1 (DMP1), and bone
      sialoprotein (BSP). Cell cultures in the presence of Biodentine were exposed to
      specific inhibitors of MAPK (U0126, SB203580, and SP600125), NF-kappaB
      (pyrrolidine dithiocarbamate), and CaMKII (KN-93) pathways to evaluate the
      regulatory effect on the expression of these markers and mineralization assay.
      RESULTS: Biodentine significantly increased alkaline phosphatase activity and
      mineralized nodule formation and the expression of OCN, DSPP, DMP1, and BSP. The
      MAPK inhibitor for extracellular signal-regulated kinase 1/2 (U0126) and Jun N
      terminal kinase (SP600125) significantly decreased the Biodentine-induced
      mineralized differentiation of hDPSCs and OCN, DSPP, DMP1, and BSP messenger RNA
      expression, whereas p38 MAPK inhibitors (SB203580) had no effect. The CaMKII
      inhibitor KN-93 significantly attenuated and the NF-kappaB inhibitor pyrrolidine
      dithiocarbamate further enhanced the up-regulation of Biodentine-induced gene
      expression and mineralization. CONCLUSIONS: Biodentine is a bioactive and
      biocompatible material capable of inducing odontoblast differentiation of hDPSCs.
      Our results indicate that this induction is regulated via MAPK and CaMKII
      pathways.

PMID- 24935540
TI  - WNT6 promotes the migration and differentiation of human dental pulp cells partly
      through c-Jun N-terminal kinase signaling pathway.
AB  - INTRODUCTION: During the dental pulp repair process, human dental pulp cells
      (HDPCs) migrate to injury sites where they may differentiate into odontoblastlike
      cells. WNT6 plays a role in dental development and can activate a noncanonical
      pathway including the c-Jun N-terminal kinase (JNK) pathway. The mechanism of
      WNT6 in dental pulp repair is still unknown. The purpose of this study was to
      explore the potential role of the WNT6/JNK signaling pathway in the promotion of
      cell migration and the differentiation of HDPCs. METHODS: The third passage of
      HDPCs were cultured in vitro and treated with WNT6 conditioned medium with or
      without the pretreatment of JNK inhibitor SP600125. The activation of JNK was
      detected by Western blot, the expression of c-Jun was quantified by reverse
      transcription polymerase chain reaction, the migration of HDPCs was determined by
      wound healing and transwell migration assays, and the differentiation of HDPCs
      was investigated using alkaline phosphatase staining and alizarin red staining.
      The expression of odontogenesis-related genes such as Runt-related transcription
      factor 2, dentin sialophosphoprotein, and dentin matrix protein 1 was quantified.
      RESULTS: WNT6 activates the JNK pathway in HDPCs and enhances cell migration,
      mineralization nodule formation, and alkaline phosphatase activation. WNT6 also
      increases the expression of Runt-related transcription factor 2, dentin
      sialophosphoprotein, and dentin matrix protein messenger RNA in HDPCs. Blockage
      of the JNK pathway in HDPCs decreases but does not completely abolish the cell
      migration and differentiation capacity induced by WNT6. CONCLUSIONS: WNT6
      activates the JNK signaling pathway in HDPCs, leading to migration and
      differentiation.

PMID- 24935541
TI  - Comparison of pulp stump wounds created by profile rotary root canal instruments
      and small-diameter fine diamond burs.
AB  - INTRODUCTION: The aim of this investigation was to evaluate and compare the pulp
      stump wounds created by the following root canal instruments: ProFile rotary
      files and small-diameter fine diamond burs. METHODS: Extracted mandibular
      premolars from adult patients with vital pulps and fully formed root canals were
      collected and stored in formalin. Within 48 hours of extraction, the periapical
      tissue was fixated to the root with a double coating of ethyl cyanoacrylate, and
      the pulp chambers were accessed with a #4 round carbide bur and high-speed
      handpiece in a traditional fashion. The pulp tissue of 10 specimens per group was
      extirpated at a level approximately 5 mm from the apex by using standard
      endodontic techniques. The specimens were then examined at *100 magnification
      under a digital microscope. Grading criteria were developed, and the wounds were
      scored. RESULTS: Wounds created by diamond burs were significantly smoother that
      those created by ProFile rotary files; the mean wound score for diamond burs was
      1.4 versus a mean wound score of 3 for ProFiles. After the author's scoring of
      the wounds, 2 endodontist graders were shown photos of each specimen in a double
      blind fashion and instructed to score each specimen as being smooth or rough. To
      validate the developed scoring system and remove potential observer bias of the
      author, the data from the double-blind observations were used to complete a cross
      tabulation for a Cohen kappa test. CONCLUSIONS: Kappa values demonstrated
      substantial inter-rater agreement for both groups.

PMID- 24935542
TI  - Influence of acidic environment on properties of biodentine and white mineral
      trioxide aggregate: a comparative study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the surface
      microhardness, compressive strength, bond strength, and morphologic
      microstructures of Biodentine (BD; Septodont, Saint Maur des Fosses, France) and
      white mineral trioxide aggregate (WMTA) after exposure to a range of acidic pH
      levels. METHODS: For each test, 4 groups of each material were exposed to pH
      values of 7.4, 6.4, 5.4, and 4.4, respectively, for 7 days. The surface hardness
      was determined using Vickers microhardness. The compressive strength and micro
      push-out bond strength were determined using the universal testing machine at a
      crosshead speed of 0.5 mm/min. The morphologic microstructures of specimens were
      evaluated using scanning electron microscopy. RESULTS: BD showed higher surface
      hardness, compressive strength, and bond strength to root dentin compared with
      WMTA after exposure to different pH values. A substantial change in the
      microstructure of BD and WMTA occurred after exposure to different pH values.
      WMTA appeared to be more sensitive to acidic pH environments than BD.
      CONCLUSIONS: BD material seems more appropriate for use when exposed to an acidic
      environment compared with WMTA.

PMID- 24935543
TI  - Mercury intrusion porosimetry and assessment of cement-dentin interface of anti
      washout-type mineral trioxide aggregate.
AB  - INTRODUCTION: One of the disadvantages of mineral trioxide aggregate (MTA) is
      washout (ie, the tendency of freshly prepared cement paste to disintegrate upon
      early contact with physiological fluids). A novel MTA (MTA Plus; Prevest Denpro,
      Jammu City, India) exhibits low washout and superior physical properties when
      mixed with a gel instead of water. When used as a root-end filler, MTA is in
      contact with both bone and root dentin. This study aimed to investigate the
      porosity and interfacial characteristics of the novel MTA mixed with water or
      antiwashout gel. METHODS: Porosity was evaluated after 1 or 28 days of immersion
      in Hank's balanced salt solution using mercury intrusion porosimetry. The root
      dentin to material interface was investigated using a scanning electron
      microscope and energy-dispersive X-ray spectroscopy complete with line scans and
      elemental maps. RESULTS: Anti-washout-type MTA Plus was found to have lower
      initial porosity than MTA Plus mixed with water although this trend was reversed
      after 28 days of immersion in physiological fluid. Both materials exhibited good
      marginal adaptation. The diffusion of silicon, calcium, and phosphorus across the
      cement/dentin interface was observed. CONCLUSIONS: MTA Plus mixed with
      antiwashout gel was found to have lower initial porosity than MTA Plus mixed with
      water. Both materials exhibited good marginal adaptation and the diffusion of
      silicon, calcium, and phosphorous across the cement/dentin interface. Thus, the
      anti-washout-type MTA can be considered to be a suitable substitute for ordinary
      MTA in all its indications.

PMID- 24935544
TI  - Influence of ultrasonic activation of 4 root canal sealers on the filling
      quality.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effects of ultrasonic
      activation on the filling quality (intratubular sealer penetration, interfacial
      adaptation, and presence of voids) of 4 epoxy resin-based sealers. METHODS:
      Eighty-four extracted human canines were divided into 4 groups (n = 20) according
      to the sealer used to obturate the root canals instrumented with F5 ProTaper
      instruments (50/05) (Dentsply Maillefer, Ballaigues, Switzerland). The canals
      were filled by the lateral compaction technique. Previously, the sealers were
      labeled with rhodamine B dye to allow analysis under a confocal microscope. At
      the time of obturation, the specimens were divided again into 2 groups (n = 10)
      according to the ultrasonic activation of the sealers: ultrasonically activated
      and nonultrasonically activated groups. All samples were sectioned at 2, 4, and 6
      mm from the apex. The percentages of voids, gaps, and dentinal sealer penetration
      segments of the canal were analyzed. RESULTS: Regarding the sealer penetration
      segments, there was a significant increase for the AH Plus (Dentsply Maillefer),
      Acroseal (Specialites Septodont, Saint Maur-des-Fosses, France), and Sealer 26
      (Dentsply Maillefer) at the 4-mm level and the AH Plus and Sealer 26 at the 6-mm
      level with ultrasonic activation (P < .05). Concerning the gaps, the ultrasonic
      activation promoted a smaller presence for all sealers at the 4- and 6-mm levels
      (P < .05). No statistical significant differences were found for the percentages
      of voids (P < .05). CONCLUSIONS: The use of ultrasonic activation of an epoxy
      resin-based sealer promoted greater dentinal sealer penetration and less presence
      of gaps.

PMID- 24935545
TI  - Evaluation of compressive strength of hydraulic silicate-based root-end filling
      materials.
AB  - INTRODUCTION: Hydraulic silicate cements such as mineral trioxide aggregate (MTA)
      have many clinical advantages. Newer hydraulic silicate materials have been
      developed that improve on the limitations of mineral trioxide aggregate such as
      the long setting time and difficult handling characteristics. The purpose of this
      study was to examine the effect of saline and fetal bovine serum (FBS) on the
      setting and compressive strength of the following hydraulic silicate cements:
      ProRoot MTA (white WMTA; Dentsply International, Tulsa Dental Specialties,
      Johnson City, TN), EndoSequence Root Repair Material (Brasseler USA, Savannah,
      GA), MTA Plus (MTAP; Avalon Biomed Inc, Bradenton, FL), and QuickSet (QS; Avalon
      Biomed Inc, Bradenton, FL). METHODS: Samples of root-end filling materials were
      compacted into polyethylene molds. Samples were exposed to FBS or saline for 7
      days. A universal testing machine was used to determine the compressive
      strengths. RESULTS: QS had significantly lower compressive strength than all
      other materials (P < .001). White MTA and MTAP mixed with liquid had lower
      compressive strengths after exposure to FBS compared with saline (P = .003).
      ERRM, MTAP mixed with gel, and QS were not affected by the exposure to FBS.
      CONCLUSIONS: New silicate-based root-end filling materials, other than QS, have
      compressive strength similar to MTA. Within the limits of this study, premixed
      materials and those mixed with antiwashout gel maintain their compressive
      strength when exposed to biological fluids.

PMID- 24935546
TI  - Torque and force induced by ProTaper universal and ProTaper next during shaping
      of large and small root canals in extracted teeth.
AB  - INTRODUCTION: The purpose of this study was to compare peak torque and force
      between ProTaper Universal (PTU) and ProTaper Next (PTN) instruments during the
      preparation of large and small root canals in extracted teeth. METHODS: Twelve
      maxillary incisors and each independent canal of 6 mesial roots of mandibular
      molars were randomly assigned to be prepared with a new set of either PTU or PTN
      instruments after a glide path was achieved. A total of 12 new sets of each
      instrument system were used. The tests were run in a standardized fashion in a
      torque-testing platform. Peak torques (Ncm) and force (N) were registered;
      analysis of variance and Tukey post hoc tests were then applied. RESULTS: Among
      instruments in the same sequence, no significant differences in peak torque and
      force were found among PTN instruments when shaping small or large root canals,
      but some PTU instruments showed statistically lower peak torque and force (P <
      .01) than others for both types of canals. Whereas PTU instruments showed
      significant differences in peak torque and force (P < .05) between large and
      small root canals, PTN instruments showed significantly lower force (P < .04) in
      large canals, but peak torque was not significantly different for upper central
      incisors or mesial mandibular root canals. CONCLUSIONS: Under the conditions of
      this study, instruments in ProTaper Next set showed greater regularity in peak
      torque for small and large canals than ProTaper Universal instruments.

PMID- 24935547
TI  - Antibacterial and anti-biofilm activity of AH plus with chlorhexidine and
      cetrimide.
AB  - INTRODUCTION: The use of root canal filling materials with antibacterial activity
      can be considered beneficial to reduce the remaining microorganisms in the root
      canal system, where Enterococcus faecalis is often found, and prevent recurrent
      infection. The aim of this study was to evaluate the antimicrobial activity and
      capacity for inhibiting E. faecalis biofilm formation of AH Plus, alone and mixed
      with chlorhexidine (CHX), cetrimide (CTR), and combinations of the two. METHODS:
      AH Plus alone and mixed with 1% and 2% CHX, 0.1%-0.5% CTR, and combinations of
      both were tested to assess antimicrobial activity by a modified direct contact
      test and determine inhibition of E. faecalis biofilm formation at 24 hours. The
      results were expressed as log10 viable counts. Eradication and inhibition of
      biofilm formation were understood as no bacterial growth or log10 reduction = 5
      with respect to the control (AH Plus alone). RESULTS: AH Plus + CHX showed a low
      antimicrobial activity with respect to the control (at 2%, log10 reduction =
      1.30). None of the tested concentrations achieved eradication or inhibition of
      biofilm. AH Plus + CTR showed a direct relationship of concentration
      antimicrobial effect, reaching a log10 reduction of 2.92 at 0.5% and inhibition
      of biofilm formation at 0.2%. With the combination CHX + CTR, lower
      concentrations were needed for the same effect, and eradication and inhibition of
      biofilm were achieved. CONCLUSIONS: The addition of CHX, CTR, or some combination
      of both to AH Plus confers it with bactericidal and anti-biofilm activity against
      E. faecalis.

PMID- 24935548
TI  - Comparison of 2 canal preparation techniques in the induction of microcracks: a
      pilot study with cadaver mandibles.
AB  - INTRODUCTION: The purpose of this pilot study in a cadaver model was to compare 2
      different shaping techniques regarding the induction of dentinal microcracks.
      METHODS: Three lower incisors from each of 6 adult human cadaver skulls were
      randomly distributed into 3 groups: the control group (CG, no instrumentation),
      the GT group (GT Profile hand files; Dentsply Tulsa Dental, Tulsa, OK), and the
      WO group (WaveOne; Dentsply Tulsa Dental). In the GT group, manual shaping in a
      crown-down sequence with GT Profile hand files was performed. In the WO group,
      Primary WaveOne files were used to the working length. Teeth were separated from
      the mandibles by careful removal of soft tissue and bone under magnification.
      Roots were sectioned horizontally at 3, 6, and 9 mm from the apex using a low
      speed saw. Color photographs at 2 magnifications (25* and 40*) were obtained.
      Three blinded examiners registered the presence of microcracks (yes/no),
      extension (incomplete/complete), direction (buccolingual/mesiodistal), and
      location. Data were analyzed with chi-square tests at P < .05. RESULTS:
      Microcracks were found in 50% (CG and GT) and 66% (WO) of teeth at 3 mm, 16.6%
      (CG) and 33.3% (GT and WO) at 6 mm, and 16.6% in all 3 groups at 9 mm from the
      apex. There were no significant differences in the incidence of microcracks
      between all groups at 3 (P = .8), 6 (P = .8), or 9 mm (P = 1). All microcracks
      were incomplete, started at the pulpal wall, and had a buccolingual direction.
      CONCLUSIONS: Within the limitations of this pilot study, a relationship between
      the shaping techniques (GT hand and WaveOne) and the incidence of microcracks
      could not be shown compared with uninstrumented controls.

PMID- 24935549
TI  - Comparison of the surface hardness among 3 materials used in an experimental
      apexification model under moist and dry environments.
AB  - INTRODUCTION: Procedures used in single-visit or multiple-visit approaches to
      apical barrier creation were used with an experimental apexification model to
      test the surface hardness of 3 materials. The purpose of this study was to
      examine the microhardness of the materials after setting in moist or dry
      conditions. METHODS: A simulated open apex and periapical environment model was
      created using polyethylene tubes placed into a porous block filled with phosphate
      buffered saline. White ProRoot Mineral Trioxide Aggregate (MTA; Dentsply Tulsa
      Dental, Tulsa, OK), EndoSequence Root Repair Material (ESRRM; Brasseler USA,
      Savannah, GA), and Biodentine (BD; Septodont, Louisville, CO) were mixed and
      placed into the apical 4 mm of the tubes (N = 15). The moist group had a damp
      cotton pellet above the test materials (mineral trioxide aggregate or ESSRM) with
      Fuji II LC (GC America, Alsip, IL) sealing the coronal segment. The dry group had
      gutta-percha placed directly against the test materials with amalgam sealing the
      coronal segment. After 10 days of storage in 100% humidity at 37 degrees C,
      samples were sectioned, and microhardness was independently measured at 2 mm and
      4 mm from the apical end. Differences were assessed using analysis of variance
      and a Tukey post hoc test (alpha = .05). RESULTS: Analysis of variance analyses
      showed no significant effect of wet or dry conditions on resultant material
      hardness. A Tukey post hoc test showed that using ESRRM and BD would not result
      in a significant difference in hardness, but using MTA would result in
      statistically significant different hardness values when compared with ESRRM or
      BD. CONCLUSIONS: Either a moist or dry environment could allow hardening of
      materials; thus, both methods could be acceptable for clinical treatment
      procedures.

PMID- 24935550
TI  - Kinematics of 2 reciprocating endodontic motors: the difference between actual
      and set values.
AB  - INTRODUCTION: The aim of this study was to evaluate the kinematics of 2
      reciprocating motors and compare it with manufacturers' declared values. METHODS:
      VDW Silver (VDW, Munich, Germany) and ATR Tecnika (Tecnika, Pistoia, Italy) were
      used in the study in 5 working modes: continuous rotation at 400 rpm on VDW
      Silver and ATR Tecnika and reciprocating motion on ATR Tecnika at 400 rpm and on
      VDW Silver in Reciproc and WaveOne mode. The polishing disk with an optical
      target was inserted in the contra-angle and recorded with a 1000-frames per
      second video camera. The direction and the amount of rotation were analyzed by
      computer, and the following kinematics parameters were calculated: engaging and
      disengaging angles, cycle rotational speeds, engaging and disengaging rotational
      speeds, net cycle angle, total cycle angle, and number of cycles to complete full
      rotation. One-way analysis of variance followed by planned pair-wise comparisons
      was used to compare kinematics parameters. The alpha error was set to 0.05.
      RESULTS: Analysis of variance revealed a difference between actual and set values
      of all 3 reciprocating modes in all kinematics parameters (P < .001). No
      significant difference between the actual engaging angle of Reciproc and that of
      the WaveOne mode was found. For reciprocating motion on the ATR Tecnika at 400
      rpm, the actual engaging and disengaging angles were 8- and 9-fold greater,
      respectively, compared with set angles (P < .001). CONCLUSIONS: The kinematics of
      reciprocating instrumentation is more complex than it seems as described only
      with angles and rotational speed. Actual kinematics values differ from
      manufacturers' declared values.

PMID- 24935551
TI  - Cyclic fatigue resistance of RaCe and Mtwo rotary files in continuous rotation
      and reciprocating motion.
AB  - INTRODUCTION: The purpose of this study was to evaluate and compare the cyclic
      fatigue resistance of RaCe (FKG Dentaire, La Chaux-de-Fonds, Switzerland) and
      Mtwo (VDW, Munich, Germany) rotary files in continuous rotation and reciprocating
      motion. METHODS: A total of 60 new rotary Mtwo and RaCe files (ISO size = 25,
      taper = 0.06, length = 25 mm) were selected and randomly divided into 4 groups (n
      = 15 each): Mtc (Mtwo NiTi files in continuous rotation), Rc (RaCe NiTi files in
      continuous rotation), Mtr (Mtwo NiTi files in reciprocating motion), and Rr (RaCe
      NiTi files in reciprocating motion). A cyclic fatigue testing device was
      fabricated with a 60 degrees  angle of curvature and a 5-mm radius. All
      instruments were rotated or reciprocated until fracture occurred. The time taken
      for each instrument to fracture and the length of the broken fragments were
      recorded. All the fractured files were analyzed under a scanning electron
      microscope to detect the mode of fracture. The Kolmogorov-Smirnov test was used
      to assess the normality of samples distribution, and statistical analysis was
      performed using the independent sample t test. RESULTS: The time taken for the
      instruments of the Mtr and Rr groups to fail under cyclic loading was
      significantly longer compared with the Mtc and Rc groups (P < .001). Scanning
      electron microscopic observations showed that the instruments of all groups had
      undergone a ductile mode of fracture. The length of the fractured segments was
      between 5 and 6 mm, which was not statistically significant among the
      experimental groups. CONCLUSIONS: Mtwo and RaCe rotary instruments showed a
      significantly higher cyclic fatigue resistance in reciprocating motion compared
      with continuous rotation motion.

PMID- 24935552
TI  - Efficacy of reciprocating instruments for removing filling material in curved
      canals obturated with a single-cone technique: a micro-computed tomographic
      analysis.
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy of nickel
      titanium reciprocating instrument techniques and passive ultrasonic irrigation
      (PUI) for retreatment in curved canals and obturated with correspondent single
      cones. METHODS: Twenty molars were selected with mesial-buccal canals with
      curvatures between 20 degrees  and 40 degrees , and they were instrumented with a
      Reciproc R25 instrument (VDW, Munich, Germany) in a reciprocating motion and
      obturated with single cones and AH Plus sealer (Dentsply Maillefer, Ballaigues,
      Switzerland). The teeth were divided into 2 groups (n = 10) according to the
      instrument used for the removal of filling material: group 1: Reciproc R25
      instrument and group 2: WaveOne Primary instrument (Dentsply Maillefer). The
      analysis of the remnant filling material was made through micro-computed
      tomographic imaging after the use of reciprocating instruments and again after
      the use of PUI with xylene. The effective time of retreatment was registered.
      RESULTS: The filling material of the root canal was efficiently removed (P < .05)
      for both groups. The percentage of removal of filling materials was 93% for the
      Reciproc group and 92% for the WaveOne group. There were no statistical
      significant differences (P > .05) between the groups in relation to the removal
      of filling material ability and the time needed for the procedure. The effective
      time for the removal of filling material was 78.7 seconds and 89.5 seconds for
      the Reciproc and WaveOne groups, respectively. CONCLUSIONS: It was concluded that
      both instruments efficiently but not completely removed the filling material from
      inside the root canals. The use of xylene with PUI increased the removal of
      filling material a little, but it was not statically significant.

PMID- 24935553
TI  - Influence of the dentinal wall on the pH of sodium hypochlorite during root canal
      irrigation.
AB  - INTRODUCTION: The purpose of this study was to evaluate the influence of dentin
      on the pH levels of different concentrations of sodium hypochlorite (NaOCl)
      solutions over time and to evaluate if preconditioning of dentin with 17% EDTA or
      agitation of the NaOCl solution influences these pH levels. METHODS: A novel
      clinically representative model that scales with the ratio of the irrigant volume
      to the dentin surface area of a human root canal was used. Three standardized
      bovine dentin bars (2 * 2 * 10 mm) were placed in a plastic test tube. A total of
      150 tubes were distributed in 29 groups. In the first experiment, the pH of
      various NaOCl solutions, with different concentrations (3%, 6%, and 9%) and
      starting pH levels (5 and 12), was monitored during exposure to dentin between 10
      and 300 seconds. In a second experiment, the effect of agitation (45 Hz) and
      pretreatment of dentin with 17% EDTA on the pH levels of various NaOCl solutions
      was studied after 30 seconds of exposure to dentin. The short-term chemical
      stability of the tested solutions was assessed for both the concentration and the
      pH. RESULTS: The exposure time (P < .001) and concentration of the NaOCl solution
      (P < .011) significantly influence the pH level after exposure to dentin.
      However, the change in pH is too small to induce a change in the irrigant
      antimicrobial/tissue dissolution capacity. CONCLUSIONS: Agitation of the irrigant
      and preconditioning of the dentin did not alter the pH (P > .05). Both the pH 5
      and pH 12 solutions were chemically stable for 1 hour.

PMID- 24935554
TI  - Incidence of apical crack initiation and propagation during the removal of root
      canal filling material with ProTaper and Mtwo rotary nickel-titanium retreatment
      instruments and hand files.
AB  - INTRODUCTION: The aim of this study was to determine the incidence of crack
      initiation and propagation in apical root dentin after retreatment procedures
      performed by using 2 rotary retreatment systems and hand files with additional
      instrumentation. METHODS: Eighty extracted mandibular premolars with single
      canals were selected. One millimeter from the apex of each tooth was ground
      perpendicular to the long axis of the tooth, and the apical surface was polished.
      Twenty teeth served as the control group, and no preparation was performed. The
      remaining 60 teeth were prepared to size 35 with rotary files and filled with
      gutta-percha and AH Plus sealer. Specimens were then divided into 3 groups (n =
      20), and retreatment procedures were performed with the following devices and
      techniques: ProTaper Universal retreatment files, Mtwo retreatment files, and
      hand files. After retreatment, the additional instrumentation was performed by
      using size 40 ProTaper, Mtwo, and hand files. Digital images of the apical root
      surface were recorded before preparation, after instrumentation, after filling,
      after retreatment, and after additional instrumentation. The images were then
      inspected for the presence of any new apical cracks and propagation. Data were
      analyzed with the logistic regression and Fisher exact tests. RESULTS: All
      experimental groups caused crack initiation and propagation after use of
      retreatment instruments. The ProTaper and Mtwo retreatment groups caused greater
      crack initiation and propagation than the hand instrument group (P < .05) after
      retreatment. Additional instrumentation with ProTaper and Mtwo instruments after
      the use of retreatment instruments caused crack initiation and propagation,
      whereas hand files caused neither crack initiation nor propagation (P < .05).
      CONCLUSIONS: This study showed that retreatment procedures and additional
      instrumentation after the use of retreatment files may cause crack initiation and
      propagation in apical dentin.

PMID- 24935555
TI  - Periradicular regenerative surgery in a maxillary central incisor: 7-year results
      including cone-beam computed tomography.
AB  - INTRODUCTION: A case of a symptomatic maxillary central incisor that underwent
      periradicular regenerative surgery with a successful long-term clinical and
      radiographic outcome is presented. METHODS: A 52-year old woman was referred to
      the Endodontology Clinic, UCL Eastman Dental Institute and Hospital, London, UK,
      in 2004 for swelling and discoloration of the maxillary right central incisor.
      There was a history of trauma 21 years previously. The tooth was endodontically
      treated 5 years before the referral. At presentation, there was diffuse facial
      swelling/erythema and a periodontal probing depth of 11 mm on the midfacial
      surface with bleeding on probing and purulent exudate. Endodontic retreatment was
      completed along with subgingival debridement. Reassessment at 6 weeks showed
      persistent purulent exudate and a probing depth up to 13 mm facially.
      Periradicular surgery was performed for the purposes of surgical exploration,
      apical resection and root-end filling with mineral trioxide aggregate, and guided
      tissue regeneration using a bone xenograft and collagen membrane. Histopathology
      confirmed the presence of a radicular cyst. RESULTS: Clinical and radiographic
      evaluation, including cone-beam computed tomographic imaging, at 7 years
      postoperatively showed a probing depth up to 3 mm and hard tissue formation
      apically, interproximally, and partly facially on the root surface. CONCLUSIONS:
      In this case of a combined endodontic-periodontic lesion in a maxillary central
      incisor, regenerative periradicular surgery led to the resolution of the defect,
      significant attachment gain, and a stable clinical and radiographic outcome after
      7 years of follow-up.

PMID- 24935556
TI  - Fusion of central incisors with supernumerary teeth: a 10-year follow-up of
      multidisciplinary treatment.
AB  - INTRODUCTION: Macrodontia of anterior teeth may occur as an isolated condition or
      as a result of fusion or gemination and may cause clinical problems such as tooth
      crowding and esthetic problems. Preliminary planning and careful management are
      often required by a dental team comprising an orthodontist, an endodontist, a
      prosthodontist, and an oral surgeon. A multidisciplinary treatment approach in a
      case with fused teeth is presented. METHODS: A 9-year-old girl presented with
      macrodontia of a left maxillary central incisor. The patient was referred to the
      orthodontic department because of a large central incisor as a result of fusion
      with an unspecific supernumerary tooth. The surgical procedure included
      sectioning off the mesial segment as far as possible, both apically and
      subgingivally, and extracting 1 of the fused supernumerary teeth. During the
      sectioning procedure, the pulp of the remaining tooth was exposed at the middle
      third of the root. Direct pulp capping was performed by an endodontist using
      mineral trioxide aggregate. Twelve weeks later, orthodontic treatment was
      commenced, and finally after a 26-month orthodontic treatment period, the central
      incisors' crown was restored using composite material. RESULTS: A 10-year
      clinical and radiographic follow-up revealed that the remaining resected central
      incisor kept its vitality, and the patient was pleased with the esthetic result.
      CONCLUSIONS: Proper interdisciplinary treatment planning of complicated cases
      such as anomalous teeth, which involve fusion to a supernumerary tooth, may lead
      to minimal invasive conservative procedures that maintain tooth vitality and
      result in a pleasing esthetic result.

PMID- 24935558
TI  - Hedgehog signaling pathway as key player in liver fibrosis: new insights and
      perspectives.
AB  - INTRODUCTION: Activation of hepatic stellate cells (HSCs) is a pivotal cellular
      event in liver fibrosis. Therefore, improving our understanding of the molecular
      pathways that are involved in these processes is essential to generate new
      therapies for liver fibrosis. Greater knowledge of the role of the hedgehog
      signaling pathway in liver fibrosis could improve understanding of the liver
      fibrosis pathogenesis. AREAS COVERED: The aim of this review is to describe the
      present knowledge about the hedgehog signaling pathway, which significantly
      participates in liver fibrosis and HSC activation, and look ahead on new
      perspectives of hedgehog signaling pathway research. Moreover, we will discuss
      the different interactions with hedgehog signaling pathway-regulated liver
      fibrosis. EXPERT OPINION: The hedgehog pathway modulates several important
      aspects of function, including cell proliferation, activation and
      differentiation. Targeting the hedgehog pathway can be a promising direction in
      liver fibrosis treatment. We discuss new perspectives of hedgehog signaling
      pathway activation in liver fibrosis and HSC fate, including DNA methylation,
      methyl CpG binding protein 2, microRNA, irradiation and metabolism that influence
      hedgehog signaling pathway transduction. These findings identify the hedgehog
      pathway as a potentially important for biomarker development and therapeutic
      targets in liver fibrosis. Future studies are needed in order to find safer and
      more effective hedgehog-based drugs.

PMID- 24935557
TI  - Performance of HLA allele prediction methods in African Americans for class II
      genes HLA-DRB1, -DQB1, and -DPB1.
AB  - BACKGROUND: The expense of human leukocyte antigen (HLA) allele genotyping has
      motivated the development of imputation methods that use dense single nucleotide
      polymorphism (SNP) genotype data and the region's haplotype structure, but the
      performance of these methods in admixed populations (such as African Americans)
      has not been adequately evaluated. We compared genotype-based-derived from both
      genome-wide genotyping and targeted sequencing-imputation results to existing
      allele data for HLA-DRB1, -DQB1, and -DPB1. RESULTS: In European Americans, the
      newly-developed HLA Genotype Imputation with Attribute Bagging (HIBAG) method
      outperformed HLA*IMP:02. In African Americans, HLA*IMP:02 performed marginally
      better than HIBAG pre-built models, but HIBAG models constructed using a portion
      of our African American sample with both SNP genotyping and four-digit HLA class
      II allele typing had consistently higher accuracy than HLA*IMP:02. However, HIBAG
      was significantly less accurate in individuals heterozygous for local ancestry (p
      <=0.04). Accuracy improved in models with equal numbers of African and European
      chromosomes. Variants added by targeted sequencing and SNP imputation further
      improved both imputation accuracy and the proportion of high quality calls.
      CONCLUSION: Combining the HIBAG approach with local ancestry and dense variant
      data can produce highly-accurate HLA class II allele imputation in African
      Americans.

PMID- 24935560
TI  - The effectiveness of exercise for the prevention and treatment of antenatal
      depression: systematic review with meta-analysis.
AB  - BACKGROUND: Antenatal depression can have harmful consequences for the mother and
      fetus. Exercise may be a useful intervention to prevent and treat antenatal
      depression. OBJECTIVES: This systematic review aims to establish whether there is
      sufficient evidence to conclude that exercise is an effective intervention for
      preventing and treating antenatal depression. SEARCH STRATEGY: Searches using
      electronic databases from MEDLINE, Cochrane Library, CINAHL, EMBASE, AMED and
      PsycINFO were performed. SELECTION CRITERIA: Randomised controlled trials (RCT)
      that compared any type of exercise intervention with any comparator in pregnant
      women were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Meta-analysis
      was performed calculating standardised mean differences (SMD). MAIN RESULTS: Six
      trials (seven comparisons) were eligible for inclusion. Meta-analysis showed a
      significant reduction in depression scores (SMD -0.46, 95% CI -0.87 to -0.05, P =
      0.03, I(2) = 68%) for exercise interventions relative to comparator groups. The
      test for subgroup differences in women who were non-depressed (one trial) (SMD 
      0.74, 95%CI -1.22 to -0.27, P = 0.002) and depressed (five trials) (SMD -0.41,
      95% CI -0.88 to 0.07, P = 0.09) at baseline was not significant (P = 0.32). The
      test for subgroup differences between aerobic (one trial) and non-aerobic
      exercise (five trials) was also nonsignificant (P = 0.32). AUTHORS' CONCLUSIONS:
      We found some evidence that exercise may be effective in treating depression
      during pregnancy but this conclusion is based on a small number of low-moderate
      quality trials with significant heterogeneity and wide confidence intervals.

PMID- 24935559
TI  - The relationship between mood and sleep in different female reproductive states.
AB  - BACKGROUND: Sleep is disrupted in depressed subjects, but it also deteriorates
      with age and possibly with the transition to menopause. The nature of interaction
      between mood, sleep, age and reproductive state is not well-defined. The aim of
      this study was to evaluate the relationship between mood and sleep among healthy
      women in different reproductive states. METHODS: We analyzed data from 11 younger
      (20-26 years), 21 perimenopausal (43-51 years) and 29 postmenopausal (58-71
      years) healthy women who participated in a study on menopause, sleep and
      cognition. The 21-item Beck Depression Inventory (BDI) was administered to assess
      mood. Subjective sleep quality was assessed with the Basic Nordic Sleep
      Questionnaire (BNSQ). Objective sleep was measured with all-night polysomnography
      (PSG) recordings. Perimenopausal and younger women were examined during the first
      days of their menstrual cycle at the follicular phase. RESULTS: Among younger
      women, less arousals associated with higher BDI total scores (p = 0.026), and
      higher SWS percentages with more dissatisfaction (p = 0.001) and depressive
      somatic symptoms (p = 0.025), but with less depressive-emotional symptoms (p =
      0.001). In specific, less awakenings either from REM sleep or SWS, respectively,
      associated with more punishment (p = 0.005; p = 0.036), more dissatisfaction (p <
      0.001; p = 0.001) and more depressive-somatic symptoms (p = 0.001; p = 0.009),
      but with less depressive-emotional symptoms (p = 0.002; p = 0.003). In
      perimenopausal women, higher BNSQ insomnia scores (p = 0.005), lower sleep
      efficiencies (p = 0.022) and shorter total sleep times (p = 0.024) associated
      with higher BDI scores, longer sleep latencies with more depressive-somatic
      symptoms (p = 0.032) and longer REM latencies with more dissatisfaction (p =
      0.017). In postmenopausal women, higher REM percentages associated with higher
      BDI total scores (p = 0.019) and more depressive-somatic symptoms (p = 0.005),
      and longer SWS latencies with more depressive-somatic symptoms (p = 0.030).
      CONCLUSIONS: Depressive symptoms measured with the total BDI scores associated
      with sleep impairment in both perimenopausal and postmenopausal women. In younger
      women, specific BDI factors revealed minor associations, suggesting that the type
      of sleep impairment can vary in relation to different depressive features. Our
      data indicate that associations between sleep and depressed mood may change in
      conjunction with hormonal milestones.

PMID- 24935561
TI  - Concentration-effect modeling based on change from baseline to assess the
      prolonging effect of drugs on QTc together with an estimate of the circadian time
      course.
AB  - As ICH E14 was adopted by the US FDA and the EU CPMC in 2005, thorough QT studies
      have routinely been analyzed by looking at the time-matched difference between
      (baseline corrected) QTcF or QTcI under the supra-therapeutic dose and placebo. A
      study is considered negative, if the two-sided 90% confidence interval for this
      difference is below 10 ms for all investigated time points. ICH E14 suggests
      including a positive control, such as moxifloxacin, for assay sensitivity.
      Concentration-response analysis has been considered a more powerful alternative,
      but its application to parallel group studies was hampered as a double difference
      of QTcF per subject cannot be calculated. Recently, a new model based on change
      from baseline with fixed time and concentration effects has been proposed. It
      allows for a placebo-corrected prediction of the drug effect with an unbiased
      standard error, and the estimate of a time effect can be used for assay
      sensitivity. We demonstrate this approach, utilizing 2 studies reported elsewhere
      with a crossover design. We compare the results from a conventional concentration
      response analysis based on the difference to placebo with results from the novel
      analysis based on the change from average baseline that includes a fixed time
      effect. 

PMID- 24935562
TI  - Serum carcinoembryonic antigen levels before initial treatment are associated
      with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations and echinoderm
      microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK)
      define specific molecular subsets of lung adenocarcinomas with distinct clinical
      features. Our purpose was to analyze clinical features and prognostic value of
      EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. PATIENTS
      AND METHODS: EGFR gene mutations and the EML4-ALK fusion gene were detected in 92
      lung adenocarcinoma patients in China. Tumor marker levels before first treatment
      were measured by electrochemiluminescence immunoassay. RESULTS: EGFR mutations
      were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at
      high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in
      patients with abnormal serum carcinoembryonic antigen (CEA) levels before the
      initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that
      a higher serum CEA level before the initial treatment was independently
      associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also
      identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In
      concordance with previous reports, younger age was a clinical feature for these
      (P=0.008). Seven of the positive cases were never smokers, and no coexistence
      with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK
      fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to
      be higher than patients with a concentration over 5 ng/ml (P=0.021). No
      significant difference was observed for time to progression and overall survival
      between EML4-ALK-positive group and EML4-ALK-negative group or between patients
      with and without an EGFR mutation. CONCLUSIONS: The serum CEA level before the
      initial treatment may be helpful in screening population for EGFR mutations or
      EML4-ALK fusion gene presence in lung adenocarcinoma patients.

PMID- 24935563
TI  - How our practice of histopathology, especially tumour pathology has changed in
      the last two decades: reflections from a major referral center in Pakistan.
AB  - Continued advances in the field of histo-pathology (and cyto-pathology) over the
      past two decades have resulted in dramatic changes in the manner in which these
      disciplines are now practiced. This is especially true in the setting of a large
      university hospital where the role of pathologists as clinicians
      (diagnosticians), undergraduate and postgraduate educators, and researchers has
      evolved considerably. The world around us has changed significantly during this
      period bringing about a considerable change in our lifestyles and the way we
      live. This is the world of the internet and the world-wide web, the world of
      Google and Wikipedia, of Youtube and Facebook where anyone can obtain any
      information one desires at the push of a button. The practice of histo (and cyto)
      pathology has also evolved in line with these changes. For those practicing this
      discipline in a poor, developing country these changes have been breathtaking.
      This is an attempt to document these changes as experienced by histo (and cyto)
      pathologists practicing in the biggest center for Histopathology in Pakistan, a
      developing country in South Asia with a large (180 million) and ever growing
      population. The Section of Histopathology, Department of Pathology and
      Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan's
      largest city has since its inception in the mid-1980s transformed the way
      histopathology is practiced in Pakistan by incorporating modern methods and
      rescuing histopathology in Pakistan from the primitive and outdated groove in
      which it was stuck for decades. It set histopathology in Pakistan firmly on the
      path of modernity and change which are essential for better patient management
      and care through accurate and complete diagnosis and more recently prognostic and
      predictive information as well.

PMID- 24935564
TI  - Role of cytokines in genesis, progression and prognosis of cervical cancer.
AB  - Cytokine research is currently at the forefront in cancer research. Deciphering
      the functions of these multiple small molecules, discovered within the cell and
      in intercellular spaces, with their abundance and pleotrophism, was initially a
      great challenge. Advances in analytical chemistry and molecular biology have made
      it possible to unravel the pathophysiological functions of these
      polypeptides/proteins which are called interleukins, chemokines, monokines,
      lymphokines and growth factors. With more than 5 million women contracting
      cervical cancer every year this cancer is a major cause of mortality and
      morbidity the world over, particularly in the developing countries. In more than
      95% of cases it is associated with human papilloma virus (HPV) infection which is
      persistent, particularly in those with a defective immune system. Although
      preventable, the mere magnitude of prevalence of HPV in the world population
      makes it a dominating current health hazard. The discovery of cytokine
      dysregulation in cervical cancer has spurted investigation into the possibility
      of using them as biomarkers in the early diagnosis of cases at high risk of
      developing cancer. Their critical role in carcinogenesis and progression of
      cervical cancer is now being revealed to a great extent. From diagnostics to
      prognosis, and now with a possible role in therapeutics and prevention of
      cervical cancer, the cytokines are being evaluated in all anticancer approaches.
      This review endeavours to capture the essence of the astonishing journey of
      cytokine research in cervical neoplasia.

PMID- 24935565
TI  - Targeting cancer with nano-bullets: curcumin, EGCG, resveratrol and quercetin on
      flying carpets.
AB  - It is becoming progressively more understandable that different phytochemicals
      isolated from edible plants interfere with specific stages of carcinogenesis.
      Cancer cells have evolved hallmark mechanisms to escape from death. Concordant
      with this approach, there is a disruption of spatiotemproal behaviour of
      signaling cascades in cancer cells, which can escape from apoptosis because of
      downregulation of tumor suppressor genes and over- expression of oncogenes.
      Genomic instability, intra-tumor heterogeneity, cellular plasticity and
      metastasizing potential of cancer cells all are related to molecular alterations.
      Data obtained through in vitro studies has convincingly revealed that curcumin,
      EGCG, resveratrol and quercetin are promising anticancer agents. Their efficacy
      has been tested in tumor xenografted mice and considerable experimental findings
      have stimulated researchers to further improve the bioavailability of these
      nutraceuticals. We partition this review into different sections with emphasis on
      how bioavailability of curcumin, EGCG, resveratrol and quercetin has improved
      using different nanotechnology approaches.

PMID- 24935566
TI  - Do not let to be late: overview of reasons for melanoma delayed diagnosis.
AB  - Melanoma of the skin is a malignant tumor, which incidence is still increasing.
      It was estimated that in the United States one person died from this cause every
      hour. The major risk factor of this disease is exposure to ultraviolet radiation,
      especially associated with the occurrence of sunburns. Patients diagnosed with
      distant metastases have median survival of 6-9 months. The aim of this paper was
      to identify the causes of delayed diagnosis of melanoma as diagnosis at an early
      stage seems to be the key to improve the survival rates. For this purpose, a
      search of medical databases such as PubMed, Google Scholar and Cancer Registers
      was conducted and an analysis of the literature from the years 1979-2013 was
      conducted.

PMID- 24935567
TI  - Hepatic steatosis: prevalence and host/viral risk factors in Iranian patients
      with chronic hepatitis B infection.
AB  - BACKGROUND: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS)
      seems to be associated with known host and viral factors which may influence the
      long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis
      and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC),
      factors associated with HS in CHB are not clearly explored. MATERIALS AND
      METHODS: 160 CHB patients were divided into two groups depending on the results
      of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group
      II comprised 89 patients without steatosis. The groups were compared in terms of
      basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP),
      serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral
      load, and histological findings. RESULTS: In terms of host factors, male gender,
      older age, BMI, high serum FBS and lipid levels were associated with HS. On the
      other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis
      did not associate with HS. On multivariate analysis, parameters of sex, BMI,
      cholesterol and FBS levels were independently associated with HS. Regarding viral
      factors, HBeAg negativity was significantly associated with HS (81.7%, p value
      0.006), but not HBV DNA level (p value 0.520). CONCLUSIONS: HS in CHB appears to
      be unrelated to the status of HBV replication. However, fibrosis progression in
      CHB is related to variable host factors. HS may be enhanced through these factors
      in HBV chronic patients.

PMID- 24935568
TI  - Determining nursing student knowledge, behavior and beliefs for breast cancer and
      breast self-examination receiving courses with two different approaches.
AB  - BACKGROUND: This study aimed to determine nursing student knowledge, behavior and
      beliefs for breast cancer and breast self-examination receiving courses with a
      traditional lecturing method (TLM) and the Six Thinking Hats method (STHM).
      MATERIALS AND METHODS: The population of the study included a total of 69 second
      year nursing students, 34 of whom received courses with traditional lecturing and
      35 of whom received training with the STHM, an active learning approach. The data
      of the study were collected pre-training and 15 days and 3 months post-training.
      The data collection tools were a questionnaire form questioning socio-demographic
      features, and breast cancer and breast self-examination (BSE) knowledge and the
      Champion's Health Belief Model Scale. The tests used in data analysis were chi
      square, independent samples t-test and paired t-test. RESULTS: The mean knowledge
      score following traditional lecturing method increased from 9.32 +/- 1.82 to
      14.41 +/- 1.94 (P<0.001) and it increased from 9.20 +/- 2.33 to 14.73 +/- 2.91
      after training with the Six Thinking Hats Method (P<0.001). It was determined
      that there was a significant increase in pre and post-training perceptions of
      perceived confidence in both groups. There was a statistically significant
      difference between pre-training, and 15 days and 3 months post-training frequency
      of BSE in the students trained according to STHM (p<0.05). On the other hand,
      there was a statistically significant difference between pre-training and 3
      months post-training frequency of BSE in the students trained according to TLM.
      CONCLUSIONS: In both training groups, the knowledge of breast cancer and BSE, and
      the perception of confidence increased similarly. In order to raise nursing
      student awareness in breast cancer, either of the traditional lecturing method or
      the Six Thinking Hats Method can be chosen according to the suitability of the
      teaching material and resources.

PMID- 24935569
TI  - Good outcomes of patients with stage IB endometrial cancer with surgery alone.
AB  - BACKGROUND: Most patients with endometrial cancer have stage I disease. Adjuvant
      therapy in stage IB (formerly IC) endometrial cancer is controversial, treatment
      options including observation or brachytherapy/ radiotherapy in grade 1-3
      patients with or without chemotherapy. The purpose of this study was to assess
      the outcomes of our patients with stage IB endometrioid endometrial cancer.
      MATERIALS AND METHODS: Sixty two patients with stage IB endometrial cancer and
      endometrioid histology were retrospectively evaluated. All patients were
      initially treated surgically by the same surgeon with comprehensive staging, i.e.
      total abdominal hysterectomy, bilateral salphingooopherectomy, bilateral pelvic
      and paraaortic lymph node dissection and omentectomy. Adjuvant radiotherapy was
      discussed with patients and utilized by those who accepted. Adjuvant chemotherapy
      was not given to any of the patients. RESULTS: Median age was 62 (range, 42-95).
      Ninety percent of the patients had grade 1-2 disease. Thirteen patients (21%)
      received intra vaginal brachytherapy (IVBT) and one received whole pelvic
      radiotherapy (WPRT). Median follow-up time was 46 months (range, 9-77 months).
      Three patients experienced recurrence (4.8%), two of them died on follow-up and
      one was still alive at last visit. Two patients with recurrence had FIGO grade 2
      tumors and one had a grade 3 tumor. Two patients (3.2%) died without evidence of
      recurrent disease. Relapse free survival at 5 years was 94.4% and overall
      survival was 93.1%. CONCLUSIONS: Patients with stage IB disease in our study
      demonstrated relatively low recurrence rates although the majority of them
      received no adjuvant treatment. Surgery alone may be sufficient for most patients
      with this stage of endometrial cancer.

PMID- 24935570
TI  - Expression of C4.4A is a potential independent prognostic factor for patients
      with gastric cancer.
AB  - C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane
      protein which is overexpressed in several human malignancies. However, there are
      few data available on C4.4A expression and its relationship with progression in
      gastric cancer. Our study was designed to explore the expression of C4.4A in
      gastric cancer and to correlate it with clinical outcome. C4.4A expression was
      studied by quantitative real-time RT-PCR and immunohistochemistry for assessment
      of correlations with clinicopathological factors. C4.4A mRNA expression was
      significantly up-regulated in gastric cancer as compared with noncancerous tissue
      (p<0.05)., being observed in 107 (88.4%) of the 121 gastric cancer cases by
      immunohistochemistry. We found that the expression of C4.4A mRNA was correlated
      with size of the tumor, depth of invasion, lymph node metastasis, distant
      metastasis and TNM stage. Moreover, patients with overexpression of C4.4A has a
      significantly worse survival (p<0.05). Further multivariable analysis indicated
      that the expression of C4.4A was an independent prognostic indicator for gastric
      cancer (p<0.05). In conclusion, overexpression of C4.4A correlates with
      metastatic potential of gastric cancer and C4.4A could be a novel independent
      prognostic marker for predicting outcome.

PMID- 24935571
TI  - DH332, a synthetic beta-carboline alkaloid, inhibits B cell lymphoma growth by
      activation of the caspase family.
AB  - AIM: The purpose of this study was to investigate anti-tumor effects and safety
      of DH332, a new beta-carboline alkaloids derivatives in vitro and in vivo.
      MATERIALS AND METHODS: The effects of DH332 on human (RAMOS RA.1) and mouse
      (J558) B lymphoma cell lines were detected using a CCK-8 kit (Cell Counting Kit
      8), and apoptosis was detected by flow cytometry with PI/annexinV staining.
      Western blotting was used to detected caspase-3 and caspase-8. Neurotoxic and
      anti-tumor effects were evaluated in animal experiments. RESULTS: DH332 exerts a
      lower neurotoxicity compared with harmine. It also possesses strong antitumor
      effects against two B cell lymphoma cell lines with low IC50s. Moreover, DH332
      could inhibit the proliferation and induce the apoptosis of RAMOS RA.1 and J558
      cell lines in a dose-dependent manner. Our results suggest that DH332 triggers
      apoptosis by mainly activating the caspase signaling pathway. In vivo studies of
      tumor-bearing BALB/c mice showed that DH332 significantly inhibited growth of
      J558 xenograft tumors. CONCLUSIONS: DH332 exerts effective antitumor activity in
      vitro and in vivo, and has the potential to be a promising drug candidate for
      lymphoma therapy.

PMID- 24935572
TI  - Chromosomal abnormalities in Pakistani children with acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Cytogenetic abnormalities have important implications in diagnosis
      and prognosis of acute leukemia and are now considered an important part of the
      diagnostic workup at presentation. Karyotype, if known at the time of diagnosis,
      guides physicians to plan appropriate management strategies for their patients.
      AIM AND OBJECTIVES: To determine the cytogenetic profile of acute lymphoblastic
      leukemia (ALL) in Pakistani children in order to have insights regarding behavior
      of the disease. MATERIALS AND METHODS: A retrospective analysis of all the cases
      of ALL (<15years old) diagnosed at Aga Khan University from January 2006 to June
      2011 was performed. Cytogenetic analysis was made for all cases using the trypsin
      Giemsa banding technique. Karyotypes were interpreted using the International
      System for Human Cytogenetic Nomenclature (ISCN) criteria. RESULTS: A total of
      153 patients were diagnosed as ALL during the study period, of which 127 samples
      successfully yielded metaphase chromosomes. The male to female ratio was 1.8:1. A
      normal karyotype was present in 51.2% (n=65) of the cases whereas 48.8% (n=62)
      had an abnormal karyotype. Most of the abnormal cases showed hyperdiploidy(13.4%)
      followed by t(9;22)(q34;q11.2) (7.08%). CONCLUSIONS: This study revealed a
      relative lack of good prognostic cytogenetic aberrations in Pakistani children
      with ALL.

PMID- 24935573
TI  - Application of tumor markers SCC-Ag, CEA, and TPA in patients with cervical
      precancerous lesions.
AB  - BACKGROUND: To determine the potential clinical utility of tumor markers CEA,
      TPA, and SCC-Ag for early detection of cervical precancerous lesions. MATERIALS
      AND METHODS: A case-control study was carried out on 120 women (46 patients with
      histologically confirmed cervical precancerous lesions and 74 healthy controls).
      The significance of serum selected tumor markers in early detection of cervical
      intraepithelial neoplasia (CIN) were assessed. RESULTS: Of the case group, the
      rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to
      the manufacturer's cut-off values of 2 ng/ml, 5 ng/ml, and 70 U/ml for SCC-Ag,
      CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA
      and TPA tests could not distinguish between case and control groups. The
      diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag,
      2.6 ng/ ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%,
      respectively. However, the area under the receiver operating characteristic curve
      was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA,
      respectively). Moreover, there was a highly significant direct correlation
      between SCC-Ag concentration and the degree of cervical precancerous lesions
      (r=0.847, p<0.001). CONCLUSIONS: The new cutoff of 0.5 for SCC-Ag test might be
      useful as a tumor marker in Iranian patients with CIN and it needs to be more
      evaluated by studies with larger populationa.

PMID- 24935574
TI  - Survival and prognostic factors for hepatocellular carcinoma: an Egyptian
      multidisciplinary clinic experience.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a dismal tumor with a high
      incidence, prevalence and poor prognosis and survival. Management of HCC
      necessitates multidisciplinary clinics due to the wide heterogeneity in its
      presentation, different therapeutic options, variable biologic behavior and
      background presence of chronic liver disease. We studied the different prognostic
      factors that affected survival of our patients to improve future HCC management
      and patient survival. MATERIALS AND METHODS: This study is performed in a
      specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo
      University, Egypt. We retrospectively analyzed the different patient and tumor
      characteristics and the primary mode of management applied to our patients.
      Further analysis was performed using univariate and multivariate statistics.
      RESULTS: During the period February 2009 till February 2013, 290 HCC patients
      presented to our multidisciplinary clinic. They were predominantly males and the
      mean age was 56.5 +/- 7.7 years. All cases developed HCC on top of cirrhosis that
      was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B
      (36.9%) and commonly presented with small single lesions. Transarterial
      chemoembolization was the most common line of treatment used (32.4%). The overall
      survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum
      bilirubin, site of the tumor and type of treatment were the significant
      independent prognostic factors for survival. CONCLUSIONS: Our main prognostic
      variables are the bilirubin level, the bilobar hepatic affection and the
      application of specific treatment (either curative or palliative).
      Multidisciplinary clinics enhance better HCC management.

PMID- 24935575
TI  - Association between Ras association domain family 1A promoter methylation and
      esophageal squamous cell carcinoma: a meta-analysis.
AB  - RASSF1A has been reported to be a candidate tumor suppressor in esophageal
      squamous cell carcinoma (ESCC). However, the association between RASSF1A promoter
      methylation and ESCC remains unclear. Eligible studies were identified through
      searching PubMed, Medline, Web of Science, and the China National Knowledge
      Infrastucture database. Studies were pooled and odds ratios (ORs) with
      corresponding confidence intervals (CIs) were calculated. Funnel plots were also
      performed to evaluate publication bias. Twelve studies involving 859 cases and
      675 controls were included in this meta-analysis. A significant association was
      observed between RASSF1A methylation and ESCC overall (OR = 11.7, 95% CI: 6.59
      20.9, z=8.36, P<0.00001). Subgroup analysis showed that the OR for heterogeneous
      tissues was 5.35 (95% CI = 2.95-9.71) while for autologous tissues it was 16.0
      (8.31-30.96). For patient sample size, the OR for the <50 subgroup was 9.92 (95%
      CI = 2.88-34.2) and for the 50 case group was 13.1 (95% CI = 6.59-25.91). The OR
      for a relationship between RASSF1A methylation and TNM stages was 0.27 (95%
      CI=0.10-0.77), whereas there were no significant differences in RASSF1A
      methylation in relation to gender and differentiation among ESCC cases. This meta
      analysis suggests a significant association between RASSF1A methylation and ESCC.

PMID- 24935576
TI  - Un-met supportive care needs of Iranian breast cancer patients.
AB  - BACKGROUND: Assessment of supportive needs is the requirement to plan any
      supportive care program for cancer patients. There is no evidence about
      supportive care needs of Iranian breast cancer patients. So, the aims of present
      study were to investigate this question and s predictive factors. MATERIALS AND
      METHODS: A descriptive- correlational study was conducted, followed by logistic
      regression analyses. The Supportive Care Needs Survey was completed by 136 breast
      cancer patients residing in Iran following their initial treatment. This assessed
      needs in five domains: psychological, health system and information, physical and
      daily living, patient care and support, and sexuality. RESULTS: Patient perceived
      needs were highest in the health systems and information (71%), and physical and
      daily living (68%) domains. Logistic regression modeling revealed that younger
      participants have more un-met needs in all domains and those with more children
      reported fewer un-met needs in patient care and support domains. In addition,
      married women had more un-met supportive care needs related to sexuality.
      CONCLUSIONS: The high rate of un-met supportive care needs in all domains
      suggests that supportive care services are desperately required for breast cancer
      patients in Iran. Moreover, services that address informational needs and
      physical and daily living needs ought to be the priority, with particular
      attention paid to younger women. Further research is clearly needed to fully
      understand supportive care needs in this cultural context.

PMID- 24935577
TI  - Rapamycin and PF4 induce apoptosis by upregulating Bax and down-regulating
      survivin in MNU-induced breast cancer.
AB  - BACKGROUND: To elucidate the role of rapamycin and PF4 on apoptosis regulation
      via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the
      growth in the 1-methyl-1-nitrosourea -induced invasive breast carcinoma model.
      MATERIALS AND METHODS: Thirty five female Sprague Dawley rats at age 21-day old
      were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3
      (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered
      intraperitionally, dosed at 70 mg/kg body weight. The rats were treated when the
      tumors reached the size of 14.5 +/- 0.5 mm and subsequently sacrificed after 5
      days. Rapamycin and PF4 were administered as focal intralesional injections at
      the dose of 20 MUg/lesion. The tumor tissue was then subjected to
      histopathological examinations for morphological appraisal and
      immunohistochemical assessment of the pro-apoptotic marker, Bax and anti
      apoptotic markers, Bcl-2 and survivin. RESULTS: The histopathological pattern of
      the untreated control cohort showed that the severity of the malignancy augments
      with mammary tumor growth. Tumors developing in untreated groups were more
      aggressive whilst those in treated groups demonstrated a transformation to a less
      aggressive subtype. Combined treatment resulted in a significant reduction of
      tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was
      significantly expressed at higher levels in the rapamycin-treated and
      rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently,
      survivin was also significantly downregulated in the rapamycin-treated and
      rapamycin+PF4-treated group and this was significantly different when compared to
      controls (p). CONCLUSIONS: In our rat model, it could be clearly shown that
      rapamycin specifically affects Bax and survivin signaling pathways in activation
      of apoptosis. We conclude that rapamycin plays a critical role in the induction
      of apoptosis in MNU-induced mammary carcinoma.

PMID- 24935578
TI  - Gastrointestinal cancer incidence in East Azerbaijan, Iran: update on 5 year
      incidence and trends.
AB  - BACKGROUND: A cancer registry program has been established in East Azerbaijan and
      this has emphasized the importance of cancers of gastrointestinal tract in this
      region. The aim of the present pathology-based cancer registry report is to renew
      epidemiologic aspects of gastrointestinal tract cancers and estimate recent
      trends. MATERIALS AND METHODS: A survey team reviewed and collected all records
      of cancer cases from all referral and valid pathology laboratories of East
      Azerbaijan province during September 2007-2011. Crude rates, age-specific rates
      of cancer incidence and annual percent change were calculated. RESULTS: The total
      newly diagnosed cancer cases (n=6,889) comprised 4,341 males (63.0%) and 2,540
      females (36.9%). Gastric cancer was the most common GI tract cancer with an ASR
      (per 105) of 23.1 for males and 7.69 for females. The ASRs for esophageal and
      colorectal cancers were 9.69 and 11.2 in males and 7.35 and 8.93 in females.
      Trend analysis showed a significant decline for esophageal cancer and increasing
      incidence for colorectal cancer in females. CONCLUSIONS: The prevalence of
      gastric cancer is high in East Azerbaijan province of Iran. This pathology based
      cancer registry showed an ascending trend for colorectal cancer and decreasing
      trend for esophageal cancer in females during 2007-2011.

PMID- 24935580
TI  - Overexpression of TRPM7 is associated with poor prognosis in human ovarian
      carcinoma.
AB  - BACKGROUND: The melastatin-related transient receptor potential 7 channel (TRPM7)
      is a nonselective cation channel that has been shown to promote tumor metastasis
      and progression. In this study, we determined the expression of TRPM7 in ovarian
      carcinomas and investigated its possible prognostic value. MATERIALS AND METHODS:
      Samples were collected from 138 patients with ovarian cancer. Expression of TRPM7
      was assessed by real-time PCR and immunohistochemistry, expressed with reference
      to an established scoring system and related to clinical pathological factors.
      Kaplan-Meier survival analysis was applied to estimate disease-free survival
      (DFS) and overall survival (OS). Univariate and multivariate cox regression
      analyses were performed to correlate TRPM7 expression levels with DFS and OS.
      RESULTS: TRPM7 was highly expressed in ovarian carcinoma and significantly
      associated with decreased disease-free survival (DFS: median 20 months vs. 42
      months, P=0.0002) and overall survival (OS: median 27 months vs. 46 months,
      P<0.001). CONCLUSION: Overexpression of TRPM7 expression is significantly
      associated with poor prognosis in patients with ovarian cancer.

PMID- 24935579
TI  - Phase II study on EANI combined with hydrochloride palonosetron for prevention of
      chemotherapy-induced nausea and vomiting following highly emetogenic
      chemotherapy.
AB  - OBJECTIVE: To investigate the electronic anti-nausea instrument (EANI) combined
      with hydrochloride palonosetron for prevention of chemotherapy-induced nausea and
      vomiting following highly emetogenic chemotherapy. METHODS: Patients who received
      highly emetogenic chemotherapy were randomly assigned to a treatment group (60
      patients) treated with EANI combined with hydrochloride palonosetron, and control
      group (also 60 patients) given only hydrochloride palonosetron. Chemotherapy
      related nausea and vomiting were observed and recorded in both groups of patients
      from the start till the end of chemotherapy. RESULTS: Complete control rates of
      vomiting in treatment and control group were 40%, and 35%, respectively, without
      any statistical ly significant difference (p> 0.05); however the response rates
      are 95.0%, 78.3%, respectively, with statistical difference (p< 0.05). Complete
      control rates of nausea in treatment and control group were 36.7%, 30%,
      respectively, without statistical difference (p> 0.05); but the response rates
      are 90.0%, 76.7%, respectively, with statistical difference (p<0.05). CONCLUSION:
      EANI combined with hydrochloride palonosetron for prevention of nausea and
      vomiting induced by chemotherapy could be more effective than hydrochloride
      palonosetron alone, and can be recommended for use in prevention and treatment of
      chemotherapy-induced nausea and vomiting following highly emetogenic
      chemotherapy.

PMID- 24935581
TI  - Tissue microarray immunohistochemical profiles of p53 and pRB in hepatocellular
      carcinoma and hepatoblastoma.
AB  - The tumour suppressor genes, p53 and pRb, are known to play important roles in
      neoplastic transformation. While molecular routes to the uncontrolled growth of
      hepatocytes, leading to primary liver cancer have generated considerable
      interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC)
      and hepatoblastoma (HB) remain to be clarified. We examined the
      immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB,
      sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour
      nuclear staining for p53 protein, 3 of these also being HbsAg positive.
      Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%)
      HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and
      one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results
      suggest that p53 does not have an important role in the development of HB but may
      contribute in HCC. There is also loss of pRb expression in the majority of HCC
      and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway.
      However, a comparison of the staining profiles of p53 and pRb proteins in HCC and
      HB did not reveal a consistent pattern to differentiate between the two types of
      tumours immunohistochemically. Hence the use of p53 and pRB protein expression
      has no contribution in the situation where there is a diagnostic difficulty in
      deciding between HCC and HB.

PMID- 24935582
TI  - Perception of breast cancer screening among Iranian women without experience of
      mammography: a qualitative study.
AB  - BACKGROUND: In Iran, there are high rates of breast cancer. It is among the five
      most common cancers, the first among cancers diagnosed, and is the leading cause
      of cancer deaths among Iranian women. OBJECTIVES: The purpose of this qualitative
      study was to explore perception of breast cancer screening among Iranian women
      who have never had a mammograph. MATERIALS AND METHODS: The current study was
      part of a qualitative research conducted by means of content analysis method and
      purposive sampling of 16 women over the age of 30 years who had not undergone
      mammography using individual semi-structured interviews. Interviews were recorded
      and transcribed verbatim. The data were under continuous consideration and
      comparative analysis in order to achieve data saturation. RESULTS: After
      codification of data, three concept categories were achieved including: i) low
      awareness, ii) worries, and iii) lack of motivation. CONCLUSIONS: Although there
      is a tendency among Iranian women to participate in breast cancer screening,
      there is a powerful cultural belief that breasts are sexual organs that should
      not be discussed publicly. Due to the incidence of breast cancer in Iranian
      women, it is critical that breast awareness education be performed by health care
      experts to explore the concepts of breast cancer and breast cancer screening.

PMID- 24935583
TI  - Association of the rs1042522 polymorphism with increased risk of prostate
      adenocarcinoma in the Pakistani population and its HuGE review.
AB  - Prostate adenocarcinoma is one of the leading causes of cancer related mortality
      in men but still limited knowledge is available about its associated functional
      SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore
      the association of this SNP with susceptibility to prostate adenocarcinoma along
      with its structural and functional impacts in the Pakistani population in a case
      control study. Three-dimensional structure of human TP53 with Pro72Arg
      polymorphism was predicted through homology modeling, refined and validated for
      detailed structure-based assessment. We also carried out a HuGE review of the
      previous available data for this polymorphism. Different genetic models were used
      to evaluate the genotypes association with the increased risk of PCa (Allelic
      contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08
      0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14,
      95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log
      Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77,
      95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP
      in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX.
      In conclusion, it was observed that the Arg coding G allele is highly associated
      with increased risk of prostate adenocarcinoma in the Pakistani population
      (p=0.000).

PMID- 24935584
TI  - Ganoderma lucidum polysaccharides target a Fas/caspase dependent pathway to
      induce apoptosis in human colon cancer cells.
AB  - Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have
      been shown to induce cell death in some kinds of cancer cells. This study
      investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon
      cancer cells and the molecular mechanisms involved. Cell proliferation, cell
      migration, lactate dehydrogenase (LDH) levels and intracellular free calcium
      levels ([Ca(2+)]i) were determined by MTT, wound-healing, LDH release and
      fluorescence assays, respectively. Cell apoptosis was observed by scanning and
      transmission electron microscopy. For the mechanism studies, caspase-8
      activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116
      cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a
      significant decrease in cell viability (P< 0.01). This study showed that the
      antitumor activity of GLP was related to cell migration inhibition, cell
      morphology changes, intracellular Ca(2+) elevation and LDH release. Also,
      increase in the levels of caspase-8 activity was involved in GLP-induced
      apoptosis. Western blotting indicated that Fas and caspase-3 protein expression
      was up-regulated after exposure to GLP. This investigation demonstrated for the
      first time that GLP shows prominent anticancer activities against the HCT-116
      human colon cancer cell line through triggering intracellular calcium release and
      the death receptor pathway.

PMID- 24935585
TI  - Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via
      regulation of mitochondrial signaling pathways.
AB  - Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma
      longa L. has been verified as an anticancer compound against several types of
      cancer. However, understanding of the molecular mechanisms by which it induces
      apoptosis is limited. In this study, the anticancer efficacy of curcumin was
      investigated in human gastric adenocarcinoma SGC-7901 cells. The results
      demonstrated that curcumin induced morphological changes and decreased cell
      viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-
      AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with
      the dissipation of mitochondrial membrane potential (MMP) and the release of
      cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up
      regulation of Bax that led to the cleavage of caspase-3 and increased cleaved
      PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin
      induced apoptosis of SGC-7901 cells might be mediated through the mitochondria
      pathway, which gives the rationale for in vivo studies on the utilization of
      curcumin as a potential cancer therapeutic compound.

PMID- 24935586
TI  - Human papillomavirus genotype distribution and E6/E7 oncogene expression in
      Turkish women with cervical cytological findings.
AB  - BACKGROUND: Infection with certain human papillomavirus (HPV) genotypes is the
      most important risk factor related with cervical cancer. The objective of the
      present study was to investigate the prevalence of HPV infection, the
      distribution of HPV genotypes and HPV E6/E7 oncogene mRNA expression in Turkish
      women with different cervical cytological findings in Mersin province, Southern
      Turkey. MATERIALS AND METHODS: A total of 476 cytological samples belonging to
      women with normal and abnormal cervical Pap smears were enrolled in the study.
      For the detection and genotyping assay, a PCR/direct cycle sequencing approach
      was used. E6/E7 mRNA expression of HPV-16, 18, 31, 33, and 45 was determined by
      type-specific real-time NASBA assay (NucliSENS EasyQ((r))HPV v1.1). RESULTS: Of
      the 476 samples, 106 (22.3%) were found to be positive for HPV DNA by PCR. The
      presence of HPV was significantly more common (p<0.001) in HSIL (6/8, 75%) when
      compared with LSIL (6/14, 42.9%), ASC-US (22/74, 29.7%) and normal cytology
      (72/380, 18.9%). The most prevalent genotypes were, in descending order of
      frequency, HPV genotype 66 (22.6%), 16 (20.8%), 6 (14.2%), 31 (11.3%), 53 (5.7%),
      and 83 (4.7%). HPV E6/E7 oncogene mRNA positivity (12/476, 2.5%) was lower than
      DNA positivity (38/476, 7.9%). CONCLUSIONS: Our data present a wide distribution
      of HPV genotypes in the analyzed population. HPV genotypes 66, 16, 6, 31, 53 and
      83 were the predominant types and most of them were potential carcinogenic types.
      Because of the differences between HPV E6/E7 mRNA and DNA positivity, further
      studies are required to test the role of mRNA testing in the triage of women with
      abnormal cervical cytology or follow up of HPV DNA positive and cytology
      negative. These epidemiological data will be important to determine the future
      impact of vaccination on HPV infected women in our region.

PMID- 24935587
TI  - Coping and quality of life in Turkish women living with ovarian cancer.
AB  - BACKGROUND: This study investigated the utilization of both problem and emotion
      focused coping strategies and their association with aspects of quality of life
      among Turkish women with ovarian cancer undergoing chemotherapy. MATERIALS AND
      METHODS: The convenience sample consisted of 228 patients in all disease stages.
      The data were collected using the brief COPE, QOL-Cancer patient tool,
      sociodemographic sheet, and medical variables were gathered from patients'
      medical charts. RESULTS: Findings reveal that quality of life is moderately high
      for this group of cancer patients, despite some specific negative facets of the
      illness and treatment experience. Acceptance, emotional support and religion were
      the most frequently used problem-focused coping strategies and self-distraction,
      venting and behavioral disengagement were the most frequently used emotion
      focused coping strategies reported by patients. Overall quality of life and,
      particularly, psychological and spiritual well- being scores of younger patients
      were lower. Patients reported using significantly more problem-focused coping
      than emotion-focused coping, and more problem-focused and less emotion-focused
      coping predicted greater quality of life. Problem-focused coping was related to
      patients' physical and spiritual well-being and emotion- focused coping was
      related inversely with psychological and social well-being. CONCLUSIONS: Coping
      strategies are influential in patient quality of life and their psychosocial
      adaptation to ovarian cancer. Psycho-oncology support programs are needed to help
      patients to frequent use of problem-focused coping and reduce emotion- focused
      coping strategies to improve overall quality of life.

PMID- 24935588
TI  - Low expression of the FoxO4 gene may contribute to the phenomenon of EMT in non
      small cell lung cancer.
AB  - Because of its importance in tumor invasion and metastasis, the epithelial
      mesenchymal transition (EMT) has become a research focus in the field of cancer.
      Recently, evidence has been presented that FoxO4 might be involved in EMT. Our
      study aimed to detect the expression of FoxO4, E-cadherin and vimentin in non
      small cell lung cancers (NSCLCs). We also investigated clinical features and
      their correlations with the markers. In our study, FoxO4, E-cadherin and vimentin
      were assessed by immunohistochemistry in a tissue microarray (TMA) containing 150
      cases of NSCLC. In addition, the expression level of FoxO4 protein was determined
      by Western blotting. The percentages of FoxO4, E-cadherin and vimentin positive
      expression in NSCLCs were 42.7%, 38.7% and 55.3%, respectively. Immunoreactivity
      of FoxO4 was low in NSCLC when compared with paired normal lung tissues. There
      were significant correlations between FoxO4 and TNM stage (P<0.001), histological
      differentiation (P=0.004) and lymph node metastasis (P<0.001), but no significant
      links with age (P=0.323), gender (P=0.410), tumor size (P=0.084), smoking status
      (P=0.721) and histological type (P=0.281). Our study showed that low expression
      of FoxO4 correlated with decreased expression of E-cadherin and elevated
      expression of vimentin. Cox regression analysis indicated FoxO4 to be an
      independent prognostic factor in NSCLC (P=0.046). These data suggested that FoxO4
      might inhibit the process of EMT in NSCLC, and might therefore be a target for
      therapy.

PMID- 24935589
TI  - Cisplatin combined with metformin inhibits migration and invasion of human
      nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9.
AB  - Metformin has been shown to be useful in reducing insulin resistance by restoring
      sensitivity. Recent evidence suggests that metformin might also possess anti
      tumour activity. This study aimed to investigate the effects of cisplatin
      combined with metformin on the proliferation, invasion and migration of HNE1/DDP
      human nasopharyngeal carcinoma (NPC) cells, and to provide a new target for
      treating metastasis. The MTT assay was used to assess viability of HNE1/DDP cells
      after exposure to different concentrations of 2, 5-diaminopyrimidine-4, 6-diol
      (DDP; 2, 4, 8, 16, and 32 MUmol.L(-1)), metformin (5, 10, 15, 20, and 25 MUmol.L(
      1)), and 4 MUmol.L(-1) of DDP combined with metformin. Wound healing and
      transwell migration assays were performed to assess cell migration and invasion,
      and expression of E-cadherin and MMP-9 was detected using Western blotting. MTT
      assay results showed that DDP could inhibit the proliferation of HNE1/DDP cells
      in a time- and concentration-dependent manner, with an IC50 of 32.0 MUmol.L(-1)
      at 24 h (P < 0.05), whereas low concentrations of DDP had almost no inhibitory
      effects on cell invasion and migration. DDP combined with metformin significantly
      inhibited cell invasion and migration. In addition, genes related to migration
      and invasion, such as those of E-cadherin and MMP-9, showed differential
      expression in the NPC cell line HNE1/DDP. In the present study, with an
      increasing concentration of metformin, the expression of MMP-9 was downregulated
      whereas that of E-cadherin was significantly upregulated. Taken together, our
      results show that cisplatin combined with metformin has effects on proliferation,
      invasion, and migration of human NPC cells.

PMID- 24935591
TI  - The metabolic syndrome is associated with more aggressive prostate cancer.
AB  - PURPOSE: The aim of this study was to analyze any association between the
      metabolic syndrome (MetS) and risk of prostate cancer (PCa) and cancer grade
      among men undergoing radical prostatectomy for PCa. MATERIALS AND METHODS: 50
      patients with MetS and 50 patients without MetS who undervent radical
      prostatectomy (RP) were included in the study. Age at biopsy, height, weight,
      digital rectal examination (DRE), pre-biopsy PSA levels, prostate volume,
      histopathologic diagnosis after surgery and Gleason scores were collected data
      from all patients. Histologic material obtained at biopsy was given a Gleason
      score; tumours with a Gleason score >=7 were considered high grade and <7 were
      considered low grade. RESULTS: The mean age at the time of biopsy was 63.7 +/-
      5.94 in patients with MetS and 61.6 +/- 6.14 in patients without MetS. Men with
      MetS had significantly lower PSA levels (p=0.01) (7.21 +/- 2.74 and 8.81 +/-
      2.72, respectively). Also, the men with MetS had higher RP tumor grade (p=0.04).
      CONCLUSIONS: Men with MetS undergoing RP have lower PSA levels and have
      significantly higher grade PCa. We must be careful for screening PCa in patients
      with MetS. Although the patients had lower PSA levels, they may have high grade
      disease.

PMID- 24935590
TI  - Are bladder neoplasms more aggresive in patients with a smoking-related second
      malignancy?
AB  - BACKGROUND: Relationships between smoking and bladder neoplasms, one of the
      common malignancies, are well-known. Different smoking-related malignancies may
      occur together. In this study, we evaluated the stage and grade of bladder
      neoplasms in patients also featuring lung or larynx cancer. MATERIALS AND
      METHODS: From January 2006 to February 2012, patients who underwent surgery for
      bladder neoplasms in our clinic were screened retrospectively. In the evaluation,
      5 patients had larynx cancer and 20 patients have lung cancer in addition, all
      having been smoking for a long time. The bladder tumor stage and grade were
      investigated in these 25 cases. RESULTS: Mean age of patients was 66.8 (49-78).
      In the evaulation, all of 5 patients who had larnyx cancer also had high grade
      urothelial cancer. One had T2 urothelial, and 3 T1 urothelial cancer. In the same
      way, all of the 20 patients with lung cancer also have high grade urothelial
      cancer, three T2, and 13 T1. Bladder cancer stage and grade were determined to be
      significantly increased in patients with concomitant bladder and lung or larynx
      cancer. CONCLUSIONS: In the patients who have smoking releated second malignancy,
      bladder cancer prognosis appears more aggressive. We now need a larger series and
      multi-center studies for understanding relevant pathophysiology.

PMID- 24935592
TI  - Diagnostic and prognostic value of miR-205 in colorectal cancer.
AB  - Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial
      cell processes such as the epithelial-mesenchymal transition (EMT) and aberrant
      expression with tumorigenesis in many types of human malignancy. This prospective
      study characterized the contribution of miR-205 to the colorectal cancer (CRC)
      tumorigenesis. The real-time reverse transcription-polymerase chain reaction was
      used to examine miR-205 levels prospectively in 36 pairs of samples of CRC tissue
      and adjacent noncancerous tissue (>2 cm from cancer tissue). In addition, the
      relationship between miR-205 levels and clinicopathological features was
      explored. The capability of miR-205 to function as a tumor marker was also
      examined. miR-205 expression levels did not show significant changes overall.
      However, miR-205 was significantly downregulated in a group of CRC samples
      compared with matched noncancerous tissue samples. Moreover, decreased miR-205
      correlated significantly with lymphatic metastasis. A receiver operating
      characteristic (ROC) curve also showed an optimum cut off point of 1.4?10-3 to
      distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we
      found lymphatic metastasis in almost 80% of the depressed samples. This study
      suggested that miR-205 could be reduced in the majority of metastatic CRCs and
      the risk of CRC metastasis may be predicted by monitoring miR-205 in patient
      samples collected at the time of the initial diagnosis. Therefore, targeting miR
      205 and its potential environmental activators might be a promising therapeutic
      option to prevent malignant progression toward metastasis. 

PMID- 24935593
TI  - 5-Fluorouracil and interleukin-2 immunochemotherapy enhances immunogenicity of
      non-small cell lung cancer A549 cells through upregulation of NKG2D ligands.
AB  - BACKGROUND: The aim of this study was to investigate the anti-cancer effects and
      mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL
      2) on non-small cell lung cancer (NSCLC) A549 cells. MATERIALS AND METHODS: In
      order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo,
      we established an A549-bearing nude mouse model. The cytotoxicity of natural
      killer (NK) cells was evaluated using a standard chromium release assay. To
      evaluate the relevance of NK cells in 5-FU+IL-2- mediated tumor inhibitory
      effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1
      antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D
      ligands (MICA/MICB) in A549 cells in vitro were also assessed. RESULTS: In A549
      bearing nude mice, combination therapy significantly inhibited tumor growth in
      comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and
      lysis of tumor cells by NK cells. Further study of mechanisms showed that NK
      cells played a vital role in the anticancer immune response of 5-FU+IL-2
      immunochemotherapy. In addition, the combination therapy synergistically
      stimulated the expression and promoter activity of MICA/MICB. CONCLUSIONS: 5-FU
      and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK
      cytotoxicity in vivo, and these effects were partly impaired after depleting NK
      cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated
      the expression and the promoter activity of MICA/MICB in A549 cells, which
      enhanced the recognition of A549 cells by NK cells. All of the data indicated
      that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for
      patients with lung cancer.

PMID- 24935594
TI  - Role of TGF-beta1 in human colorectal cancer and effects after cantharidinate
      intervention.
AB  - Effects of transforming growth factor-beta (TGF-beta) were investigated in human
      colorectal cancer, and the influence of cantharidinate in inhibiting TGF-beta1
      expression was explored. Relationships among TGF-beta1 and sex, age, tumor size,
      tumor location, tumor stage were also analyzed. H and E and immunohistochemistry
      staining were employed to assess colorectal cancer and TGF-beta1 expression,
      respectively. Then, HCT-116 CRC cells were randomly divided into four groups,
      controls, no serum-treated, chemotherapy and cantharidinate-treated.
      Immunohistochemistry and real-time PCR were employed to assess the expression of
      TGF-beta1 in CRC cells. Our data showed that the expression of TGF-beta1 might be
      associated with tumor size and tumor location (P<0.05). The expression of TGF
      beta1 in CRC groups was higher than in adjacent groups (P<0.05). In addition, the
      expression of TGF-beta1 in cantharidinate-treated group was much lower than in
      CRC group (P<0.05). Taken together, these results suggest that TGF-beta1 plays an
      important role in CRC development. Cantharidinate might inhibit the expression of
      TGF-beta1 and control the development of colorectal cancer.

PMID- 24935595
TI  - Survival analysis for white non-Hispanic female breast cancer patients.
AB  - BACKGROUND: Race and ethnicity are significant factors in predicting survival
      time of breast cancer patients. In this study, we applied advanced statistical
      methods to predict the survival of White non-Hispanic female breast cancer
      patients, who were diagnosed between the years 1973 and 2009 in the United States
      (U.S.). MATERIALS AND METHODS: Demographic data from the Surveillance
      Epidemiology and End RESULTS (SEER) database were used for the purpose of this
      study. Nine states were randomly selected from 12 U.S. cancer registries. A
      stratified random sampling method was used to select 2,000 female breast cancer
      patients from these nine states. We compared four types of advanced statistical
      probability models to identify the best-fit model for the White non- Hispanic
      female breast cancer survival data. Three model building criterion were used to
      measure and compare goodness of fit of the models. These include Akaike
      Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance
      Information Criteria (DIC). In addition, we used a novel Bayesian method and the
      Markov Chain Monte Carlo technique to determine the posterior density function of
      the parameters. After evaluating the model parameters, we selected the model
      having the lowest DIC value. Using this Bayesian method, we derived the
      predictive survival density for future survival time and its related inferences.
      RESULTS: The analytical sample of White non-Hispanic women included 2,000 breast
      cancer cases from the SEER database (1973-2009). The majority of cases were
      married (55.2%), the mean age of diagnosis was 63.61 years (SD = 14.24) and the
      mean survival time was 84 months (SD = 35.01). After comparing the four
      statistical models, results suggested that the exponentiated Weibull model (DIC=
      19818.220) was a better fit for White non-Hispanic females' breast cancer
      survival data. This model predicted the survival times (in months) for White non
      Hispanic women after implementation of precise estimates of the model parameters.
      CONCLUSIONS: By using modern model building criteria, we determined that the data
      best fit the exponentiated Weibull model. We incorporated precise estimates of
      the parameter into the predictive model and evaluated the survival inference for
      the White non-Hispanic female population. This method of analysis will assist
      researchers in making scientific and clinical conclusions when assessing survival
      time of breast cancer patients.

PMID- 24935596
TI  - Significance of ABO-Rh blood groups in response and prognosis in breast cancer
      patients treated with radiotherapy and chemotherapy.
AB  - BACKGROUND: To evaluate whether ABO-Rh blood groups have significance in the
      treatment response and prognosis in patients with non-metastatic breast cancer.
      MATERIALS AND METHODS: We retrospectively evaluated files of 335 patients with
      breast cancer who were treated between 2005 and 2010. Demographic data, clinic-
      pathological findings, treatments employed, treatment response, and overall and
      disease-free survivals were reviewed. Relationships between clinic-pathological
      findings and blood groups were evaluated. RESULTS: 329 women and 6 men were
      included to the study. Mean age at diagnosis was 55.2 years (range: 26-86). Of
      the cases, 95% received chemotherapy while 70% were given radiotherapy and 60.9%
      adjuvant hormone therapy after surgery. Some 63.0% were A blood group, 17.6% O,
      14.3% B and 5.1% AB. In addition, 82.0% of the cases were Rh-positive. Mean
      follow-up was 24.5 months. Median overall and progression-free survival times
      were 83.9 and 79.5 months, respectively. Overall and disease-free survival times
      were found to be higher in patients with A and O blood groups (p<0.05). However
      rates did not differ with the Rh-positive group (p=0.226). In univariate and
      multivariate analyses, ABO blood groups were identified as factors that had
      significant effects on overall and disease-survival times (p=0.011 and p=0.002).
      CONCLUSIONS: It was seen that overall and disease-free survival times were higher
      in breast cancer patients with A and O blood groups when compared to those with
      other blood groups. It was seen that A and O blood groups had good prognostic
      value in patients with breast cancer.

PMID- 24935597
TI  - No detection of 'high-risk' human papillomaviruses in a group of Iranian women
      with breast cancer.
AB  - The presence of viral DNA in breast cancer cells is controversial. However, some
      studies have revealed a possible role for the human papillomavirus in the
      pathogenesis of breast cancer. The aim of the present study was to investigate
      the presence of HPV-DNA in breast tissue in a group of Iranian women with and
      without breast cancer and identification of the detected HPV types. Paraffin
      embedded specimens from 65 malignant breast cancer cases and 65 cases with benign
      breast lesions were investigated for presence of HPV-DNA by nested polymerase
      chain reaction. We found HPV-DNA in 22 (33.8%) of the breast cancer specimens.
      All non-cancerous specimens were negative. Low and high-risk HPV types, including
      HPV-6 (26.2%), HPV-16 (1.5%), HPV-35 (1.5%), HPV-52 (1.5%), and HPV-11 (1.5%)
      were detected in our study. HPV-6 was the most prevalent type in the breast
      cancer specimens. Although high-risk HPV types have been shown to have a major
      role in cervix cancer, there have been no data that support the same relevance
      for other types of malignancies. Furthermore, presence of low-risk HPV types in
      malignancies still is a matter of debate. The data presented in this study
      indicates a strong need for epidemiological studies correlating different HPV
      types in human breast cancer.

PMID- 24935598
TI  - The COX-2 -765 G>C polymorphism is associated with increased risk of gastric
      carcinogenesis in the Chinese Hui ethnic population.
AB  - BACKGROUND: The Chinese Hui ethnic group has diverse origins, including Arab,
      Persian, Central Asian, and Mongol. The standardized mortality rate of gastric
      cancer in the Hui population is higher than the overall Chinese population. In
      this study, we investigated whether COX-2-765G>C polymorphism, an extensively
      studied polymorphism, contributes to gastric cancer and its precursor lesions
      (GPL) in the Chinese Hui ethnic group. MATERIALS AND METHODS: COX-2-765G>C
      polymorphism was determined by pyrosequencing in 100 gastric cancer cases, 102
      gastric cancerand its precursor lesions cases and 105 controls. Data were
      statistically analyzed using Chi-square tests and logistic regression models.
      RESULTS: Among the Chinese Hui ethnic group COX-2 -765 C allele carriers were at
      increased risk for gastric cancer (OR=1.977, 95%CI=1.104-3.541). We also found an
      interaction between COX-2 -765 C carriers and Helicobacter pylori infection and
      eating pickled vegetables. CONCLUSIONS: Our findings suggest a multi-step process
      of gene-environment interaction contributes to gastric carcinogenesis.

PMID- 24935599
TI  - Lack of association between CYP1A1 polymorphisms and risk of bladder cancer: a
      meta-analysis.
AB  - BACKGROUND: The effects of CYP1A1 gene polymorphisms on the risk of bladder
      cancer (BC) remain controversial. We carried out a meta-analysis to clarify the
      role of CYP1A1 gene polymorphisms in BC. MATERIAL AND METHODS: A comprehensive
      literature search was conducted up to November 20, 2013. Odds ratios (ORs) with
      95% confidence intervals (CIs) were used to estimate the strength of the
      association. Meta-regression, subgroup analysis, sensitivity analysis and
      publication bias were also performed. RESULTS: Eight studies involving 1,059 BC
      cases and 1,061 controls were included. The meta-analysis showed that there was
      no significant association between the two common mutations of CYP1A1 and BC
      risk. For the I1e462Val A/G polymorphism with GG vs. AA the OR was 1.47 (95 % CI=
      0.70-3.07, P =0.308). For the MspI T/C polymorphism, though a slight trend was
      found this was not statistically nonsignificant (CC vs.TT, OR = 1.24, 95 % CI=
      0.98-1.58, P =0.078). Subgroup analyses by ethnicity also found no obvious
      association between CYP1A1 and BC risk. CONCLUSION: The present meta-analysis
      suggests that CYP1A1 polymorphism is not associated with bladder cancer risk.

PMID- 24935600
TI  - Increased argonaute 2 expression in gliomas and its association with tumor
      progression and poor prognosis.
AB  - BACKGROUND: Previous studies have showed that argonaute 2 is a potential factor
      related to genesis of several cancers, however, there have been no reports
      concerning gliomas. METHODS: Paraffin specimens of 129 brain glioma cases were
      collected from a hospital affiliated to Binzhou Medical University from January
      2008 to July 2013. We examined both argonaute 2 mRNA and protein expression by
      real-time quantitative PCR (qRT-PCR), Western blot analysis, and
      immunohistochemistry (IHC). The survival curves of the patients were determined
      using the Kaplan-Meier method and Cox regression, and the log-rank test was used
      for statistical evaluations. RESULTS: Both argonaute 2 mRNA and protein were
      upregulated in high-grade when compared to low-grade tumor tissues. Multivariate
      analysis revealed that argonaute 2 protein expression was independently
      associated with the overall survival (HR=4.587, 95% CI: 3.001-6.993; P=0.002),
      and that argonaute 2 protein expression and WHO grading were independent
      prognostic factors for progression-free survival (HR=4.792, 95% CI: 3.993-5.672;
      P<0.001, and HR=2.109, 95% CI: 1.278-8.229; P=0.039, respectively). Kaplan-Meier
      analysis with the log-rank test indicated that high argonaute 2 protein
      expression had a significant impact on overall survival (P=0.0169) and
      progression-free survival (P=0.0324). CONCLUSIONS: The present study showed that
      argonaute 2 expression is up-regulated in gliomas. Argonaute 2 might also serve
      as a novel prognostic marker.

PMID- 24935601
TI  - Potential impact of atelectasis and primary tumor glycolysis on F-18 FDG PET/CT
      on survival in lung cancer patients.
AB  - BACKGROUND: Atelectasis is an important prognostic factor that can cause
      pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In
      this study, we aimed to investigate the potential impact of atelectasis and PET
      parameters on survival and the relation between atelectasis and PET parameters.
      MATERIALS AND METHODS: The study consisted of patients with lung cancer with or
      without atelectasis who underwent (18)F-FDG PET/CT examination before receiving
      any treatment. (18)F-FDG PET/CT derived parameters including tumor size, SUVmax,
      SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area,
      atelectasis volume, and histological and TNM stage were considered as potential
      prognostic factors for overall survival. RESULTS: Fifty consecutive lung cancer
      patients (22 patients with atelectasis and 28 patients without atelectasis,
      median age of 65 years) were evaluated in the present study. There was no
      relationship between tumor size and presence or absence of atelectasis, nor
      between presence/absence of atelectasis and TLG of primary tumors. The overall
      one-year survival rate was 83% and median survival was 20 months (n=22) in the
      presence of atelectasis; the overall one-year survival rate was 65.7% (n=28) and
      median survival was 16 months (p=0.138) in the absence of atelectasis. With
      respect to PFS; the one-year survival rate of AT+ patients was 81.8% and median
      survival was 19 months; the one-year survival rate of AT- patients was 64.3% and
      median survival was 16 months (p=0.159). According to univariate analysis, MTV,
      TLG and tumor size were significant risk factors for PFS and OS (p<0.05).
      However, SUVmax was not a significant factor for PFS and OS (p>0.05).
      CONCLUSIONS: The present study suggested that total lesion glycolysis and
      metabolic tumor volume were important predictors of survival in lung cancer
      patients, in contrast to SUVmax. In addition, having a segmental lung atelectasis
      seems not to be a significant factor on survival.

PMID- 24935602
TI  - Under-use of radiotherapy in stage III bronchioaveolar lung cancer and socio
      economic disparities in cause specific survival: a population study.
AB  - BACKGROUND: This study used the receiver operating characteristic curve (ROC) to
      analyze Surveillance, Epidemiology and End RESULTS (SEER) bronchioaveolar
      carcinoma data to identify predictive models and potential disparity in outcomes.
      MATERIALS AND METHODS: Socio-economic, staging and treatment factors were
      assessed. For the risk modeling, each factor was fitted by a Generalized Linear
      Model to predict cause specific survival. The area under the ROC was computed.
      Similar strata were combined to construct the most parsimonious models. A random
      sampling algorithm was used to estimate modeling errors. Risk of cause specific
      death was computed for the predictors for comparison. RESULTS: There were 7,309
      patients included in this study. The mean follow up time (S.D.) was 24.2 (20)
      months. Female patients outnumbered male ones 3:2. The mean (S.D.) age was 70.1
      (10.6) years. Stage was the most predictive factor of outcome (ROC area of 0.76).
      After optimization, several strata were fused, with a comparable ROC area of
      0.75. There was a 4% additional risk of death associated with lower county family
      income, African American race, rural residency and lower than 25% county college
      graduate. Radiotherapy had not been used in 2/3 of patients with stage III
      disease. CONCLUSIONS: There are socio-economic disparities in cause specific
      survival. Under-use of radiotherapy may have contributed to poor outcome.
      Improving education, access and rates of radiotherapy use may improve outcome.

PMID- 24935603
TI  - Association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk in
      Chinese.
AB  - The X-ray repair cross-complementing group 1 protein (XRCC1) plays important
      roles in the DNA base excision repair pathway which may influence the development
      of lung cancer. This study aimed to evaluate the potential association of the
      XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created
      restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods
      were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung
      cancer patients and 379 controls. Associations between the genetic polymorphism
      and lung cancer risk were determined with an unconditional logistic regression
      model. Our data suggested that the distribution of allele and genotype in lung
      cancer patients was significantly different from that of controls. The XRCC1
      c.1178G>A genetic polymorphism was associated with an increased risk of lung
      cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22
      1.90, p<0.001). The allele A and genotype AA may contribute to risk of lung
      cancer. These preliminary results suggested that the XRCC1 c.1178G>A genetic
      polymorphism is statistically associated with lung cancer risk in the Chinese
      population.

PMID- 24935604
TI  - 8-60hIPP5(m)-induced G2/M cell cycle arrest involves activation of
      ATM/p53/p21(cip1/waf1) pathways and delayed cyclin B1 nuclear translocation.
AB  - Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls
      gene expression and cell cycle progression. The active mutant IPP5 (8
      60hIPP5(m)), the latest member of the inhibitory molecules for PP1, has been
      shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to
      elucidate the underlying mechanisms, the present study assessed overexpression of
      8-60hIPP5(m) in HeLa cells. Flow cytometric and biochemical analyses showed that
      overexpression of 8-60hIPP5(m) induced G2/M-phase arrest, which was accompanied
      by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM,
      p53, p21(cip1/waf1) and Cdc2, suggesting that 8-60hIPP5(m) induces G2/M arrest
      through activation of the ATM/p53/p21(cip1/waf1)/Cdc2/ cyclin B1 pathways. We
      further showed that overexpression of 8-60hIPP5(m) led to delayed nuclear
      translocation of cyclin B1. 8-60hIPP5(m) also could translocate to the nucleus in
      G2/M phase and interact with pp1alpha and Cdc2 as demonstrated by co
      precipitation assay. Taken together, our data demonstrate a novel role for 8
      60hIPP5(m) in regulation of cell cycle in HeLa cells, possibly contributing to
      the development of new therapeutic strategies for cervix carcinoma.

PMID- 24935605
TI  - Assessing misdiagnosis of relapse in patients with gastric cancer in Iran cancer
      institute based on a hidden Markov multi-state model.
AB  - BACKGROUND: Accurate assessment of disease progression requires proper
      understanding of natural disease process which is often hidden and unobservable.
      For this purpose, disease status should be clearly detected. But in most diseases
      it is not possible to detect such status. This study, therefore, aims to present
      a model which both investigates the unobservable disease process and considers
      the error probability in diagnosis of disease states. MATERIALS AND METHODS: Data
      from 330 patients with gastric cancer undergoing surgery at the Iran Cancer
      Institute from 1995 to 1999 were analyzed. Moreover, to estimate and assess the
      effect of demographic, diagnostic and clinical factors as well as medical and
      post-surgical variables on transition rates and the probability of misdiagnosis
      of relapse, a hidden Markov multi-state model was employed. RESULTS:
      Classification errors of patients in alive state without a relapse (e21) and with
      a relapse (e12) were 0.22 (95% CI: 0.04-0.63) and 0.02 (95% CI: 0.00-0.09),
      respectively. Only variables of age and number of renewed treatments affected
      misdiagnosis of relapse. In addition, patient age and distant metastasis were
      among factors affecting the occurrence of relapse (state1->state2) while the
      number of renewed treatments and the type and extent of surgery had a significant
      effect on death hazard without relapse (state2->state3) and death hazard with
      relapse (state2->state3). CONCLUSIONS: A hidden Markov multi-state model provides
      the possibility of estimating classification error between different states of
      disease. Moreover, based on this model, factors affecting the probability of this
      error can be identified and researchers can be helped with understanding the
      mechanisms of classification error.

PMID- 24935606
TI  - Diabetes mellitus as a risk factor for high grade renal cell carcinoma.
AB  - BACKGROUND: Diabetes is a chronic disease characterized by impaired fasting blood
      glucose that leads to disturbances in various organs. In this study, we evaluated
      relationships between tumor size and grade in a population of diabetic and non
      diabetic patients with renal cell carcinoma. MATERIALS AND METHODS: Between 2007
      2013, in our clinic radical nephrectomy performed to 310 patients for renal
      tumors and pathology reported renal cell carcinoma cases were enrolled in the
      study. Patients with and without a history of diabetes regarding fasting glucose
      and HgA1c levels were evaluated during surgery for tumor size and Fuhrman grade.
      RESULTS: Diabetes was found in 95 patients. The mean age of the patients with and
      without diabetes mellitus was 64.3 (40-79) and 58.4 (31-87) years, respectively.
      In the diabetes group 51% of patients had a tumor size over 7 cm and 54% a tumor
      grade over Fuhrman 3. The respective figures in the non-diabetes group were 35%
      and 30% (p<0.05 in both cases). CONCLUSIONS: Renal cancer appears more aggressive
      in patients with diabetes. In this study lifestyle and risk factors with diabetes
      regulation were observed to be important for renal cancer patients. Multicenter
      studies are needed in larger series for more accurate results.

PMID- 24935608
TI  - Comparison of risk factors for pediatric convulsive status epilepticus when
      defined as seizures >= 5 min versus seizures >= 30 min.
AB  - PURPOSE: To identify risk factors (RF) of pediatric convulsive status epilepticus
      (SE) and to determine whether defining SE as seizures >= 5 min (SE5) or seizures
      >= 30 min (SE30) would modify the risk factors identified. METHODS: Retrospective
      case-control study. We included patients 1 month to 21 years of age at the time
      of convulsive SE. We compared the characteristics of patients with SE (cases)
      versus those without SE (controls) using two different seizure duration
      thresholds: 5 min and 30 min. RESULTS: 1062 patients (54% males) were enrolled.
      The median (p25-p75) age at the episode was 6.4 (2.8-11.8) years. 444 (41.8%)
      patients had SE5 and 149 (14%) patients had SE30. On univariate analysis, risk
      factors for SE were not markedly different when considering a 5 or 30 min
      threshold. Compared to their respective controls patients with both SE5 and SE30
      were younger at the age of seizure onset and at the age of SE, were on more
      antiepileptic drugs (AEDs) at baseline, had a higher rate of changes in AEDs in
      the three months prior to the episode, were more likely to have developmental
      delay at baseline, and a higher mortality rate. A higher baseline seizure
      frequency, and a higher increase in seizure frequency prior to the index episode
      were seen only in SE5. CONCLUSION: This series identifies RF which predict
      convulsive SE in pediatric patients. These RF are similar when considering a 5
      min or a 30 min threshold for the definition of SE.

PMID- 24935607
TI  - An unequal burden: poor patient-provider communication and sickle cell disease.
AB  - OBJECTIVE: To assess disparities in the quality of healthcare provider
      communication experienced by African-American adults with and without sickle cell
      disease (SCD) in the U.S. METHODS: Poor provider communication was assessed by
      the Provider Communication subscale of the Consumer Assessment of Healthcare
      Plans and Systems survey. The SCD sample was obtained from participants in a
      multicenter observational study of healthcare experiences. The national African
      American sample data was obtained from published national estimates. RESULTS: The
      SCD sample was more likely than the national sample to report poor communication
      in 3 out of 4 communication domains: listening (22.3% vs. 11.5%, p<0.0001);
      showing respect (26.1% vs. 9.5%, p<0.0001); and spending enough time (38.3% vs.
      16.2%, p<0.0001). Differences were consistent in young, but not old, patients and
      showed some variation by self-reported health status and education. CONCLUSIONS:
      The communication difficulties experienced by persons with SCD do not appear
      reducible to their predominantly African-American race, but may result from more
      disease-specific factors. PRACTICE IMPLICATIONS: Healthcare providers should take
      particular care in recognizing and demonstrating recommended communication skills
      with SCD patients as these patients may be particularly vulnerable to, and
      cognizant of, poor quality interactions.

PMID- 24935609
TI  - Frailty predicts waitlist mortality in liver transplant candidates.
AB  - We aimed to determine whether frailty, a validated geriatric construct of
      increased vulnerability to physiologic stressors, predicts mortality in liver
      transplant candidates. Consecutive adult outpatients listed for liver transplant
      with laboratory Model for End-Stage Liver Disease (MELD) >= 12 at a single center
      (97% recruitment rate) underwent four frailty assessments: Fried Frailty, Short
      Physical Performance Battery (SPPB), Activities of Daily Living (ADL) and
      Instrumental ADL (IADL) scales. Competing risks models associated frailty with
      waitlist mortality (death/delisting for being too sick for liver transplant). Two
      hundred ninety-four listed liver transplant patients with MELD >= 12, median age
      60 years and MELD 15 were followed for 12 months. By Fried Frailty score >=3, 17%
      were frail; 11/51 (22%) of the frail versus 25/243 (10%) of the not frail
      died/were delisted (p = 0.03). Each 1-unit increase in the Fried Frailty score
      was associated with a 45% (95% confidence interval, 4-202) increased risk of
      waitlist mortality adjusted for MELD. Similarly, the adjusted risk of waitlist
      mortality associated with each 1-unit decrease (i.e. increasing frailty) in the
      Short Physical Performance Battery (hazard ratio 1.19, 95% confidence interval
      1.07-1.32). Frailty is prevalent in liver transplant candidates. It strongly
      predicts waitlist mortality, even after adjustment for liver disease severity
      demonstrating the applicability and importance of the frailty construct in this
      population. 

PMID- 24935610
TI  - Children select unhealthy choices when given a choice among snack offerings.
AB  - Out-of-school-time programs serve snacks to millions of children annually. State
      and national snack policies endorse serving more-healthful options, such as
      fruits, yet often allow less-healthful options, such as cookies and chips, to be
      served simultaneously. To date, no studies have examined the choices children
      make when provided with disparate snack options in out-of-school-time programs.
      An experimental study with randomized exposures was conducted that exposed
      children (5 to 10 years old) to the following conditions: whole or sliced fruit;
      whole/sliced fruit, sugar-sweetened snacks (eg, cookies) and flavored salty (eg,
      nacho cheese-flavored tortilla chips) snacks; and whole/sliced fruit and less
      processed/unflavored grain snacks (eg, pretzels), during a 2-week period
      representing 18 snack occasions (morning and afternoon) during summer 2013. The
      percentage of children who selected snacks, snack consumption, and percent of
      serving wasted were calculated and analyzed using repeated-measures analyses of
      variance with Bonferroni adjustments. A total of 1,053 observations were made.
      Sliced fruit was selected more than whole fruit across all conditions. Fruit
      (sliced or whole) was seldom selected when served simultaneously with sugar
      sweetened (6% vs 58%) and flavored salty (6% vs 38%) snacks or unflavored grain
      snacks (23% vs 64%). More children consumed 100% of the sugar-sweetened (89%) and
      flavored salty (82%) snacks compared with fruit (71%); 100% consumption was
      comparable between fruit (59%) and unflavored grain snacks (49%). Approximately
      15% to 47% of fruit was wasted, compared with 8% to 38% of sugar-sweetened,
      flavored salty, and unflavored grain snacks. Snack policies that encourage out-of
      school-time programs to serve fruit require clear language that limits offering
      less-healthful snack options simultaneously.

PMID- 24935611
TI  - Race/ethnicity and income in relation to the home food environment in US youth
      aged 6 to 19 years.
AB  - BACKGROUND: The home food environment is complex and has the potential to
      influence dietary habit development in young people. Several factors may
      influence the home food environment, including income and race/ethnicity.
      OBJECTIVE: To examine the relationship of income and race/ethnicity with three
      home food environment factors (ie, food availability frequency, family meal
      patterns [frequency of family and home cooked meals], and family food
      expenditures). DESIGN: A cross-sectional analysis of the National Health and
      Nutrition Examination Survey (NHANES). PARTICIPANTS: A total of 5,096 youth aged
      6 to 19 years from a nationally representative sample of US individuals
      participating in NHANES 2007-10. STATISTICAL ANALYSES PERFORMED: Prevalence of
      food availability frequency was assessed for the entire sample, race/ethnicity,
      poverty income ratio (PIR), and race/ethnicity stratified by PIR. Mean values of
      family meal patterns and food expenditures were calculated based on
      race/ethnicity, PIR, and race/ethnicity stratified by PIR using analysis of
      variance and least squares means. Tests of main effects were used to assess
      differences in food availability prevalence and mean values of family meal
      patterns and food expenditures. RESULTS: Non-Hispanic whites had the highest
      prevalence of salty snacks (51.1%+/-1.5%) and fat-free/low-fat milk (39.2%+/
      1.7%) always available. High-income homes had the highest prevalence of fruits
      (75.4%+/-2.4%) and fat-free/low-fat milk (38.4%+/-2.1%) always available.
      Differences were found for prevalence of food availability when race/ethnicity
      was stratified by PIR. Non-Hispanic blacks had the lowest prevalence of fat
      free/low-fat milk always available across PIR groups. Differences in mean levels
      of family meal patterns and food expenditures were found for race/ethnicity, PIR,
      and race/ethnicity stratified by PIR. CONCLUSIONS: Race/ethnicity and PIR appear
      to influence food availability, family meal patterns, and family food
      expenditures in homes of youth. Knowledge of factors that influence the home food
      environment could assist in developing effective strategies to improve food
      environments for young people.

PMID- 24935612
TI  - Whole-cell imaging of the budding yeast Saccharomyces cerevisiae by high-voltage
      scanning transmission electron tomography.
AB  - Electron tomography using a high-voltage electron microscope (HVEM) provides
      three-dimensional information about cellular components in sections thicker than
      1 MUm, although in bright-field mode image degradation caused by multiple
      inelastic scattering of transmitted electrons limit the attainable resolution.
      Scanning transmission electron microscopy (STEM) is believed to give enhanced
      contrast and resolution compared to conventional transmission electron microscopy
      (CTEM). Samples up to 1 MUm in thickness have been analyzed with an intermediate
      voltage electron microscope because inelastic scattering is not a critical
      limitation, and probe broadening can be minimized. Here, we employed STEM at 1
      MeV high-voltage to extend the useful specimen thickness for electron tomography,
      which we demonstrate by a seamless tomographic reconstruction of a whole, budding
      Saccharomyces cerevisiae yeast cell, which is ~3 MUm in thickness. High-voltage
      STEM tomography, especially in the bright-field mode, demonstrated sufficiently
      enhanced contrast and intensity, compared to CTEM tomography, to permit
      segmentation of major organelles in the whole cell. STEM imaging also reduced
      specimen shrinkage during tilt-series acquisition. The fidelity of structural
      preservation was limited by cytoplasmic extraction, and the spatial resolution
      was limited by the relatively large convergence angle of the scanning probe.
      However, the new technique has potential to solve longstanding problems of image
      blurring in biological specimens beyond 1 MUm in thickness, and may facilitate
      new research in cellular structural biology.

PMID- 24935613
TI  - Physiological response during activity programs using Wii-based video games in
      patients with cystic fibrosis (CF).
AB  - Patients with cystic fibrosis (CF) are characterized by an abnormal ventilation
      response that limits the exercise capacity. Exercise training increases exercise
      capacity, decreases dyspnea and improves health-related quality of life in CF.
      Adherence to pulmonary rehabilitation programs is a key factor to guarantee
      optimal benefits and a difficult goal in this population. The aim of this study
      was to determine the physiological response during three Nintendo WiiTM video
      game activities (VGA) candidates to be used as training modalities in patients
      with CF. METHOD: 24 CF patients (age 12.6+/-3.7 years; BMI 18.8+/-2.9kgm(-2);
      FEV1 93.8+/-18.8%pred) were included. All participants performed, on two separate
      days, 3 different VGA: 1) Wii Fit Plus (Wii-Fit); 2) Wii Active (Wii-Acti), and
      3) Wii Family Trainer (Wii-Train), in random order during 5min. The obtained
      results were compared with the 6-min walk test (6MWT). The physiological
      variables [oxygen uptake (VO2), minute ventilation (VE), and heart rate (HR)]
      were recorded using a portable metabolic analyzer. RESULTS: During all VGA and
      6MWT, VO2 reached a plateau from the 3rd min. Compared with the 6MWT (1024.2+/
      282.2mLm(-1)), Wii-Acti (1232.2+/-427.2mLm(-1)) and Wii-Train (1252.6+/-360.2mLm(
      1)) reached higher VO2 levels during the last 3min (p<0.0001 in both cases),
      while Wii-Fit (553.8+/-113.2mLm(-1)) reached significantly lower levels of VO2
      (p<0.001). Similar effects were seen for the ventilatory volume (VE). No
      differences in dyspnea and oxygen saturation were seen between the different
      modalities. All patients were compliant with all three WiiTM modalities.
      CONCLUSION: Active video game are well tolerated by patients with CF. All the
      modalities evaluated imposed a constant load but were associated with different
      physiological responses reflecting the different intensities imposed. Wii-Acti
      and Wii-Train impose a significantly high metabolic demand comparable to the
      6MWT. Further research is needed to evaluate the effects of VGA as a training
      program to increase exercise capacity for CF patients.

PMID- 24935614
TI  - Hubbard U calculations for gap states in dilute magnetic semiconductors.
AB  - On the basis of constrained density functional theory, we present ab initio
      calculations for the Hubbard U parameter of transition metal impurities in dilute
      magnetic semiconductors, choosing Mn in GaN as an example. The calculations are
      performed by two methods: (i) the Korringa-Kohn-Rostoker (KKR) Green function
      method for a single Mn impurity in GaN and (ii) the full-potential linearized
      augmented plane-wave (FLAPW) method for a large supercell of GaN with a single Mn
      impurity in each cell. By changing the occupancy of the majority t2 gap state of
      Mn, we determine the U parameter either from the total energy differences E(N +
      1) and E(N - 1) of the (N +/- 1)-electron excited states with respect to the
      ground state energy E(N), or by using the single-particle energies for n(0) +/-
      1/2 occupancies around the charge-neutral occupancy n0 (Janak's transition state
      model). The two methods give nearly identical results. Moreover the values
      calculated by the supercell method agree quite well with the Green function
      values. We point out an important difference between the 'global' U parameter
      calculated using Janak's theorem and the 'local' U of the Hubbard model.

PMID- 24935616
TI  - A parallel diagnostic accuracy study of three molecular panels for the detection
      of bacterial gastroenteritis.
AB  - Culture-dependent detection of gastroenteric bacteria is labour-intensive and
      does not provide results in a clinically relevant time frame. Several
      commercially available multiplex molecular panels are now available which may be
      more sensitive and could potentially provide rapid results. We compared the
      diagnostic accuracy, turnaround time and ease of use of three such molecular
      panels: the RIDA(r)GENE Bacterial Stool and EHEC/EPEC Panels (R-Biopharm AG,
      Darmstadt, Germany), the FTD(r) Bacterial Gastroenteritis Panel (Fast Track
      Diagnostics, Junglinster, Luxembourg) and the BD MAXTM Enteric Bacterial Panel
      (Becton Dickinson GmbH, Heidelberg, Germany). The results from 116 retrospective
      selected and 318 prospective unselected stool samples were compared with
      conventional culture-based techniques using a gold standard for a positive test
      of either culture or agreement in two of the three molecular panels. For most
      targets, the molecular panels were more sensitive than culture, detecting an
      additional 13 cases that culture missed. The laboratory turnaround time was under
      3 h for all molecular panels, compared with 66.5 h for culture. The BD MAXTM
      panel was the fastest, easiest to use and most flexible.

PMID- 24935615
TI  - Molecular revolution in the diagnosis of microbial brain abscesses.
AB  - A brain abscess is a life-threatening infection, frequently with serious
      sequelae. Culture-based methods present many limitations and do not enable an
      exhaustive documentation of the bacterial flora. 16S rRNA-based amplification,
      cloning, and high-throughput sequencing have dramatically increased the number of
      identified agents of brain abscesses, showing that the causative flora is
      polymicrobial in up to 40 % of cases, with the presence of at least one anaerobic
      bacterium. In contrast, real-time polymerase chain reaction (PCR) technology is
      an appealing alternative to culture-based methods for diagnosing brain abscesses
      due to its speed, sensitivity, and specificity. Molecular typing is available for
      several bacterial and fungal genera, and this user-friendly tool is accessible
      for the clinical microbiology laboratory to diagnose microbes involved in a brain
      abscess. This article reviews the applications of the currently available tools
      for the etiological diagnosis of a brain abscess.

PMID- 24935617
TI  - Antibiotic overuse and Clostridium difficile: a teachable moment.

PMID- 24935618
TI  - The frequency of precocious segregation of sister chromatids in mouse female
      meiosis I is affected by genetic background.
AB  - Mammalian female gametes frequently suffer from numerical chromosomal
      aberrations, the main cause of miscarriages and severe developmental defects. The
      underlying mechanisms responsible for the development of aneuploidy in oocytes
      are still not completely understood and remain a subject of extensive research.
      From studies focused on prevalence of aneuploidy in mouse oocytes, it has become
      obvious that reported rates of aneuploidy are strongly dependent on the method
      used for chromosome counting. In addition, it seems likely that differences
      between mouse strains could influence the frequency of aneuploidy as well;
      however, up till now, such a comparison has not been available. Therefore, in our
      study, we measured the levels of aneuploidy which has resulted from
      missegregation in meiosis I, in oocytes of three commonly used mouse strains-CD
      1, C3H/HeJ, and C57BL/6. Our results revealed that, although the overall
      chromosomal numerical aberration rates were similar in all three strains, a
      different number of oocytes in each strain contained prematurely segregated
      sister chromatids (PSSC). This indicates that a predisposition for this type of
      chromosome segregation error in oocyte meiosis I is dependent on genetic
      background. 

PMID- 24935619
TI  - Bayesian hierarchical model for multiple repeated measures and survival data: an
      application to Parkinson's disease.
AB  - Multilevel item response theory models have been increasingly used to analyze the
      multivariate longitudinal data of mixed types (e.g., continuous and categorical)
      in clinical studies. To address the possible correlation between multivariate
      longitudinal measures and time to terminal events (e.g., death and dropout),
      joint models that consist of a multilevel item response theory submodel and a
      survival submodel have been previously developed. However, in multisite studies,
      multiple patients are recruited and treated by the same clinical site. There can
      be a significant site correlation because of common environmental and
      socioeconomic status, and similar quality of care within site. In this article,
      we develop and study several hierarchical joint models with the hazard of
      terminal events dependent on shared random effects from various levels. We
      conduct extensive simulation study to evaluate the performance of various models
      under different scenarios. The proposed hierarchical joint models are applied to
      the motivating deprenyl and tocopherol antioxidative therapy of Parkinsonism
      study to investigate the effect of tocopherol in slowing Parkinson's disease
      progression.

PMID- 24935620
TI  - Translational researches on leaf senescence for enhancing plant productivity and
      quality.
AB  - Leaf senescence is a very important trait that limits yield and biomass
      accumulation of agronomic crops and reduces post-harvest performance and the
      nutritional value of horticultural crops. Significant advance in physiological
      and molecular understanding of leaf senescence has made it possible to devise
      ways of manipulating leaf senescence for agricultural improvement. There are
      three major strategies in this regard: (i) plant hormone biology-based leaf
      senescence manipulation technology, the senescence-specific gene promoter
      directed IPT system in particular; (ii) leaf senescence-specific transcription
      factor biology-based technology; and (iii) translation initiation factor biology
      based technology. Among the first strategy, the P SAG12 -IPT autoregulatory
      senescence inhibition system has been widely explored and successfully used in a
      variety of plant species for manipulating senescence. The vast majority of the
      related research articles (more than 2000) showed that crops harbouring the
      autoregulatory system displayed a significant delay in leaf senescence without
      any abnormalities in growth and development, a marked increase in grain yield and
      biomass, dramatic improvement in horticultural performance, and/or enhanced
      tolerance to drought stress. This technology is approaching commercialization.
      The transcription factor biology-based and translation initiation factor biology
      based technologies have also been shown to be very promising and have great
      potentials for manipulating leaf senescence in crops. Finally, it is speculated
      that technologies based on the molecular understanding of nutrient recycling
      during leaf senescence are highly desirable and are expected to be developed in
      future translational leaf senescence research. 

PMID- 24935621
TI  - PEG-mediated osmotic stress induces premature differentiation of the root apical
      meristem and outgrowth of lateral roots in wheat.
AB  - Water stress is one of the major environmental stresses causing growth
      retardation and yield loss of plants. In the past decades, osmotic adjustment,
      antioxidant protection, and stomatal movement have been extensively studied, but
      much less attention has been paid to the study of root system reprogramming to
      maximize water absorption and survival under water stress. Here, it is shown that
      polyethylene glycol (PEG)-simulated mild and moderate osmotic stress induced
      premature differentiation of the root apical meristem (RAM). It is demonstrated
      that RAM premature differentiation is a conserved adaptive mechanism that is
      widely adopted by various plants to cope with osmotic stress simulated by PEG
      8000, and the occurrence of RAM premature differentiation is directly related to
      stress tolerance of plants. It is shown that the osmotic stress-induced premature
      differentiation caused growth cessation of primary roots allowing outgrowth of
      lateral roots. This work has uncovered a key mechanism for controlling the
      plastic development of the root system by which plants are capable of survival,
      growth, or reproduction under water stress. 

PMID- 24935623
TI  - Association between OGG1 gene single nucleotide polymorphisms and risk of
      pancreatic cancer in Chinese.
AB  - Previous studies have suggested that the 8-oxoguanine DNA glycosylase gene (OGG1)
      has potentially influenced the risk of pancreatic cancer. The objective of this
      study was to assess the association between single nucleotide polymorphisms
      (SNPs) of OGG1 gene and risk of pancreatic cancer. A case-control study has been
      conducted in 370 pancreatic cancer patients and 395 healthy controls. Genotypes
      were determined using the polymerase chain reaction-restriction fragment length
      polymorphism and DNA sequencing methods. The association analysis was evaluated
      by the unconditional logistic regression test. Our data suggested that the
      distributions of alleles and genotypes were statistically different between
      pancreatic cancer patients and healthy controls. The c.307G>C SNP was associated
      with the decreased risk of pancreatic cancer (C vs. G: OR 0.73, 95 % CI 0.59
      0.91, P = 0.006). As for c.828A>G SNP, the significantly decreased risk of
      pancreatic cancer was detected (G vs. A: OR 0.74, 95 % CI 0.59-0.92, P = 0.006).
      The allele C of c.307G>C and allele G of c.828A>G SNPs might be associated with a
      protection from pancreatic cancer. Findings from this study indicate that OGG1
      SNPs are associated with pancreatic cancer risk in Chinese Han population and
      could be useful molecular biomarkers for assessing the risk of pancreatic cancer.

PMID- 24935622
TI  - Involvement of multiple phytoene synthase genes in tissue- and cultivar-specific
      accumulation of carotenoids in loquat.
AB  - Differences in carotenoid accumulation between tissues and cultivars is common in
      plants. White-fleshed loquat cultivars had low levels of carotenoids in the
      flesh, but accumulated carotenoids in peel when ripe, and the leaves accumulated
      similar carotenoids to those in the red-fleshed loquat cultivars. The catalytic
      activity and expression patterns of four phytoene synthase (PSY) genes, EjPSY1,
      EjPSY2A, EjPSY2B, and EjPSY3, were analysed to understand their roles in
      different loquat (Eriobotrya japonica Lindl.) types. EjPSY1 was responsible for
      carotenoid synthesis in the fruit peel but not the flesh, whereas EjPSY2A was
      responsible for carotenoid accumulation in flesh of ripening fruit. A mutant
      EjPSY2A (d) , with the same tissue specificity and expression level as EjPSY2A,
      but lacking the C-terminal region and corresponding catalytic activity, was
      discovered in white-fleshed varieties, explaining the lack of carotenoids in the
      white flesh. The catalytic role of EjPSY2B was most significant in leaves. The
      tissue-specific expression of EjPSY1 and EjPSY2B explained well how peel and leaf
      tissues can still accumulate carotenoids in white-fleshed cultivars, which have
      lost the functional EjPSY2A. EjPSY3 mRNA abundance was ~1000-fold less than that
      of other PSY mRNAs in all tissues examined. In addition, neither the normal sized
      transcript nor two alternatively spliced forms, EjPSY3alpha in LYQ and EjPSY3beta
      in BS cultivars, encoded functional enzymes, and it is concluded that EjPSY3
      plays no role in carotenoid accumulation. In addition, it was noted that
      recruitment of PSY genes for expression in specific tissues of different plants
      has occurred independently of gene structure and evolutionary origin. 

PMID- 24935624
TI  - Luminal breast cancer classification according to proliferative indices:
      clinicopathological characteristics and short-term survival analysis.
AB  - The classification of luminal breast cancer has been a popular topic regarding
      its heterogeneity with distinct biological features and clinical outcomes. This
      study aimed to assess the power of proliferative indices (Ki67 and histological
      grade) to determine various clinicopathological characteristics and survival in
      luminal disease. A total of 541 patients with stage I-III luminal breast cancer
      were enrolled. Subtypes were determined using proliferative indices and were
      compared with clinicopathological variables and short-term survival. The
      significance of various treatments was evaluated in a subgroup of pN0 (lymph node
      negative) patients. Histological grade, independent of other variables, was a
      better predictor in the ER/PR+, human epidermal growth factor receptor 2 (Her-2)
      subgroup (p = 0.011) and the pN0 subgroup (p = 0.044) compared with Ki67, which
      only showed significance in the ER/PR+, Her-2 subgroup (p = 0.008). Neither grade
      nor Ki67 was associated with outcomes in the luminal Her-2 class. In pN0
      patients, various treatments did not show significance in short-term survival.
      Histological grade outperformed Ki67 as a determinant for the stratification of
      luminal class regarding short-term survival. Chemotherapy most likely did not
      provide additional benefit to pN0 patients with luminal breast cancer compared
      with endocrine therapy.

PMID- 24935625
TI  - Prognostic and predictive role of ERCC1 protein expression in locally advanced
      stage III non-small cell lung cancer.
AB  - Systemic therapy improves the survival and quality of life of patients with
      advanced stage non-small cell lung cancer (NSCLC). Several new therapeutic
      options have emerged for advanced NSCLC, incorporating novel cytotoxicity agents
      (taxanes, gemcitabine, pemetrexed) and molecular-targeted agents (erlotinib,
      bevacizumab) and the optimal prognostic marker for survival remains unclear. The
      aim of the present study was to assess the prognostic value of the
      clinicopathologic features and excision repair cross-complementation group-1
      (ERCC1) in locally advanced NSCLC patients that received cisplatin-based
      chemotherapy. Clinical data concerning 80 patients with histopathologically
      confirmed non-small cell lung cancer who are planned to receive cisplatin-based
      adjuvant chemotherapy were collected. The protein expression levels for ERCC1 are
      immunohistochemical examined in 80 patients. The relationship between the ERCC1
      protein expression level and the clinical outcomes of the patients is then
      observed. The 3-year survival rate and median survival time of stage III NSCLC
      received chemotherapy with/without concurrent chemoradiotherapy were 20 % and 10
      months, respectively. Survival of patients with ERCC1-negative tumors was
      significantly longer than those with ERCC1-positive tumors (p = 0.0001).
      Prognostic factors with overall survival were performance status, cigarette
      smoking, stage, weight loss and ERCC1. While as regard progression-free survival
      prognostic factors were stage, weight loss, ERCC1 and degree of positivity of
      ERCC1 progression. It was found that ERCC1 protein expression might play an
      important role in the prognosis of locally advanced NSCLC patients treated with
      cisplatin-based adjuvant chemotherapy.

PMID- 24935626
TI  - Insertion of a metallic guide-wire in the pleural cavity as a complication in
      tunneled indwelling pleural catheter placement.

PMID- 24935627
TI  - Group typicality, group loyalty and cognitive development.
AB  - Over the course of childhood, children's thinking about social groups changes in
      a variety of ways. Developmental Subjective Group Dynamics (DSGD) theory
      emphasizes children's understanding of the importance of conforming to group
      norms. Abrams et al.'s study, which uses DSGD theory as a framework, demonstrates
      the social cognitive skills underlying young elementary school children's
      thinking about group norms. Future research on children's thinking about groups
      and group norms should explore additional elements of this topic, including
      aspects of typicality beyond loyalty.

PMID- 24935628
TI  - The "Princess Mirror": Exemplars of the Use of the Mirror in Nursing Practice.
AB  - PROBLEM: Incorporating mirrors into nursing is a relatively new field of research
      and practice. The focus of two studies was to explore (a) the meaning of women's
      mirror experiences following a mastectomy and (b) the experience of viewing self
      in the mirror for women who were terminally ill. The goal of the research was to
      establish a conceptual foundation for the development of nursing mirror
      interventions. METHODS: Open-ended questions and dialogical engagement in one-to
      one audio-taped interviews were used in both studies. Ricoeur's hermeneutic
      phenomenology was used to analyze the findings. FINDINGS: Four concepts were
      uncovered in the experience of viewing self in the mirror: decision, seeing,
      understanding, and consent. CONCLUSION: Exemplar composite case studies across
      the care continuum are provided as examples of the way in which mirrors may be
      utilized in nursing practice.

PMID- 24935629
TI  - Analysis on long-range residue-residue communication using molecular dynamics.
AB  - We investigated the possibility of inter-residue communication of side chains in
      barstar, an 89 residue protein, using mutual information theory. The normalized
      mutual information (NMI) of the dihedral angles of the side chains was obtained
      from all-atom molecular dynamics simulations. The accumulated NMI from an
      explicit solvent equilibrated trajectory (600 ns) with free backbone exhibits a
      parabola-shaped distribution over the inter-residue distances (0-36 A): smaller
      at the end regimes but larger in the middle regime. This analysis, plus several
      other measures, does not find unusual long-range communication for free backbone
      in explicit solvent simulations.

PMID- 24935630
TI  - Founding of the International Journal of Obesity: a journey in medical
      journalism.

PMID- 24935631
TI  - Three-dimensional carbon nanotube networks with a supported nickel oxide nanonet
      for high-performance supercapacitors.
AB  - A three-dimensional porous carbon nanotube film with a supported NiO nanonet was
      prepared by simple electrophoretic deposition and hydrothermal synthesis, which
      could deliver a high specific capacitance of 1511 F g(-1) at a high discharge
      current of 50 A g(-1) due to the significantly improved transport of the
      electrolyte and electrons. 

PMID- 24935632
TI  - IL-18 gene polymorphisms in aphthous stomatitis vs. Behcet's disease in a cohort
      of Egyptian patients.
AB  - OBJECTIVE: A clinical investigation of the potential correlation of two single
      nucleotide polymorphisms at -137 (G/C) and -607 (C/A) in the promoter region of
      the IL-18 gene, with the susceptibility to aphthous stomatitis and Behcet's
      disease. PATIENT AND METHODS: This study included 80 aphthous stomatitis patients
      and 80 patients with Behcet's disease. Eighty healthy subjects were enrolled as a
      control group. IL-18 single-nucleotide polymorphisms at -607 and -137 regions
      were analyzed using polymerase chain reaction-restriction fragment length
      polymorphism analysis. RESULTS: The genotype and allele distributions of the two
      regions did not differ significantly between patients with aphthous stomatitis
      and controls. The genotype and allele distributions at -607 were significantly
      different between patients with Behcet's disease [CC (P = 0.044), C allele (P =
      0.043), A allele (P = 0.043)], and controls. The frequency of the GG genotype at
      position -137 in patients with Behcet's disease was associated only with a higher
      rate of ocular manifestations (OR= 1.4, CI= 0.76-2.7, P = 0.031). CONCLUSION: IL
      18 gene polymorphisms were not associated with any susceptibility to aphthous
      stomatitis, while a positive association was found with patients with Behcet's
      disease regarding -607 promoter site. Moreover, patients with Behcet's disease
      carrying the GG genotype at position -137 had a higher risk of developing ocular
      manifestations.

PMID- 24935634
TI  - How we involved rural clinicians in teaching ethics to medical students on rural
      clinical placements.
AB  - BACKGROUND: The task of engaging senior medical students in ethical inquiry while
      on rural clinical placements has received minimal attention in the medical
      education literature. As there is an international trend for medical students to
      undertake part or all of their clinical training in rural areas, the need to
      deliver clinically relevant ethics teaching in a sustainable manner has emerged
      as a challenge for medical schools. Clinicians tend to be hesitant about
      delivering this kind of teaching. What we did: We introduced a novel teaching
      program which involved recruiting, training and supporting experienced rural
      clinicians to facilitate a series of Rural Ethics Ward Rounds with the senior
      medical students on extended rural placements. EVALUATION: The clinical
      facilitators expressed some initial uncertainty with the teaching model, but
      generally reported a positive experience, including significant professional
      benefits such as increased ethical awareness and opportunity for self-reflection.
      CONCLUSION: This model enables experienced rural clinicians to facilitate student
      development in ethical awareness and skill, and requires relatively low demands
      on academic time and resources.

PMID- 24935633
TI  - Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits
      osteoclastogenesis in vitro.
AB  - Genetic studies in human and mice have pinpointed an essential role of Notch
      signaling in osteoblast and osteoclast differentiation during skeletal
      development and bone remodeling. However, the factors and pathways regulating
      Notch activation in bone cells remain largely unknown. In this in vitro study, we
      have provided evidence that two of the TspanC8 subfamily members of tetraspanins,
      Tspan-5 and Tspan-10, are up-regulated during osteoclast differentiation and
      knockdown of their expression by shRNAs dramatically inhibits osteoclastogenesis.
      Loss of Tspan-5 and Tspan-10 in osteoclast lineage cells results in attenuation
      of ADAM10 maturation and Notch activation. Therefore, these two tetraspanins play
      a critical role in osteoclast formation, at least in part, by modulating Notch
      signaling pathway. 

PMID- 24935636
TI  - Risking 'Safety': Breast Cancer, Prognosis, and the Strategic Enterprise of Life.
AB  - Living in modern biopolitical risk culture might be seen as synonymous with
      living in prognosis time, in the sense that risk of illness is endlessly forecast
      (prognosticated) in the broad social arena. 'Safety,' in this context, is framed
      as the anticipatory guarding against risk or disease in order to 'make live.'
      Thinking of risk and safety in these ways is limited, however, in that the
      prognosis cannot account for the individual's life or death drama. This paper
      asks: how are we to understand the constellation of risk, prognosis, and safety
      in relation to 'the subject in breast cancer prognosis'? 

PMID- 24935635
TI  - PARP inhibition delays progression of mitochondrial encephalopathy in mice.
AB  - Mitochondrial disorders are deadly childhood diseases for which therapeutic
      remedies are an unmet need. Given that genetic suppression of the nuclear enzyme
      poly (adenine diphosphate-ribose) polymerase(PARP)-1 improves mitochondrial
      functioning, we investigated whether pharmacological inhibition of the enzyme
      affords protection in a mouse model of a mitochondrial disorder. We used mice
      lacking the Ndufs4 subunit of the respiratory complex I (Ndufs4 knockout [ KO]
      mice); these mice undergo progressive encephalopathy and die around postnatal day
      50. Mice were treated daily with the potent PARP inhibitor N-(6-oxo-5,6
      dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide hydrochloride (PJ34);
      neurological parameters, PARP activity, and mitochondrial homeostasis were
      evaluated. We found that mice receiving N-(6-oxo-5,6-dihydrophenanthridin-2-yl)
      (N,N-dimethylamino)acetamide hydrochloride from postnatal day 30 to postnatal day
      50 show reduced neurological impairment, and increased exploratory activity and
      motor skills compared with vehicle-treated animals. However, drug treatment did
      not delay or reduce death. We found no evidence of increased PARP activity within
      the brain of KO mice compared with heterozygous, healthy controls. Conversely, a
      10-day treatment with the PARP inhibitor significantly reduced basal poly(ADP
      ribosyl)ation in different organs of the KO mice, including brain, skeletal
      muscle, liver, pancreas, and spleen. In keeping with the epigenetic role of PARP
      1, its inhibition correlated with increased expression of mitochondrial
      respiratory complex subunits and organelle number. Remarkably, pharmacological
      targeting of PARP reduced astrogliosis in olfactory bulb and motor cortex, but
      did not affect neuronal loss of KO mice. In light of the advanced clinical
      development of PARP inhibitors, these data emphasize their relevance to treatment
      of mitochondrial respiratory defects. 

PMID- 24935637
TI  - Congenital unilateral facial nerve agenesis.

PMID- 24935638
TI  - Supply and demand analysis of the current and future US neurology workforce.

PMID- 24935639
TI  - Fatigue in the acute phase after first stroke predicts poorer physical health 18
      months later.

PMID- 24935641
TI  - Optimizing methyl-eugenol aromatherapy to maximize posttreatment effects to
      enhance mating competitiveness of male Bactrocera carambolae (Diptera:
      Tephritidae).
AB  - Methyl-eugenol (ME) (1,2-dimethoxy-4-(2-propenyl)benzene), a natural
      phytochemical, did enhance male Bactrocera carambolae Drew & Hancock (Diptera:
      Tephritidae) mating competitiveness 3 d after ingestion. Enhanced male mating
      competitiveness can significantly increase the effectiveness of the sterile
      insect technique (SIT). ME application to mass reared sterile flies by feeding is
      infeasible. ME application by aromatherapy however, would be a very practical way
      of ME application in fly emergence and release facilities. This approach was
      shown to enhance mating competitiveness of B. carambolae 3 d posttreatment (DPT).
      Despite this added benefit, every additional day of delaying release will reduce
      sterile fly quality and will add cost to SIT application. The present study was
      planned to assess the effects of ME-aromatherapy on male B. carambolae mating
      competitiveness 1DPT and 2DPT. ME aromatherapy 1DPT or 2DPT did enhance mating
      competitiveness of B. carambolae males whereas ME feeding 1DPT and 2DPT did not.
      Male mating competitiveness was enhanced by the ME aromatherapy irrespective if
      they received 1DPT, 2DPT or 3DPT. ME aromatherapy, being a viable approach for
      its application, did enhance mating competitiveness of male B. carambolae 1 d
      posttreatment as ME feeding did 3 d after ingestion. 

PMID- 24935642
TI  - Retroperitoneoscopic-guided cool-tip radiofrequency ablation of adrenocortical
      aldosteronoma.
AB  - PURPOSE: To analyze the feasibility, safety, and therapeutic effects of
      retroperitoneoscopic-guided cool-tip radiofrequency ablation (RCRFA) used for the
      treatment of adrenocortical aldosteronoma. PATIENTS AND METHODS: We performed a
      retrospective comparison of RCRFA (n=12) and laparoscopic partial adrenalectomy
      (LPA) (n=26) in the patients with solitary aldosterone-producing adenoma in our
      center from 2006 to 2009. Intraoperative and follow-up data were reviewed for
      clinical parameters and hormone levels. Univariate analysis was performed to
      measure the consistency of these clinical parameters preoperatively and
      postoperatively. RESULTS: All patients presented hypertension, hypokalemia, and
      high aldosterone/renin ratio (ARR>30) preoperatively and were finally
      histologically confirmed as aldosteronoma. Technical success rate of these two
      procedures was 100%. Every patient was followed up for more than 3 years (mean
      49.2+/-15.6 months). There was no evidence of residual or recurrent lesion
      postoperatively. ARR declined significantly postoperatively compared with
      preoperatively (54.33+/-24.90 vs 5.50+/-3.30 in the RCRFA group and 51.45+/-29.12
      vs 6.67+/-3.75 in the LPA group, p<0.05). Hypokalemia was resolved in all
      patients after the surgery. A majority of patients (91.7% in the RCRFA group and
      96.2% in the LPA group) were cured without any further need of antihypertensive
      medication or experienced an improvement in hypertension. Antihypertensive
      medications reduced significantly after surgical procedures. RCRFA and LPA
      demonstrated similar therapeutic effects. Compared with LPA, RCRFA provided a
      shorter operative time (65.6+/-13.5 minutes vs 86.0+/-16.5 minutes in LPA,
      p<0.05), less blood loss (20.0+/-11.3 mL vs 60.8+/-52.0 mL in LPA, p<0.05), and
      lower complication rate (16.7% vs 26.9% in LPA). CONCLUSIONS: RCRFA might be an
      alternative for LPA in selected patients with adrenocortical aldosteronoma. Due
      to limited sample size, more experience is necessary to validate this procedure.

PMID- 24935643
TI  - Nb-doped CaO: an efficient electron donor system.
AB  - Transition metal atoms incorporated into insulating materials (oxides in
      particular) can deeply modify their adsorption properties. In particular, charge
      transfer to adsorbed species can be induced by the presence of substitutional
      dopants, which introduce new electronic states in the band gap of the host
      crystal. Here we show, by means of density functional theory calculations, that
      Nb represents an excellent dopant to turn the rather inactive CaO(100) surface
      into an electron-rich support. The charge transfer ability of the doped material
      is shown by comparing the adsorption properties of the electronegative Au atoms
      on pure and Nb-doped CaO. While in the first case the CaO-Au bonding is
      relatively weak and the Au atom is essentially neutral, in the Nb-doped system a
      much stronger adhesion is found due to a net charge transfer from the Nb dopant
      and to the formation of a gold anion. This mechanism occurs also for Nb in high
      oxidation states. Nb is thus an excellent modifier of the calcium oxide
      properties. 

PMID- 24935644
TI  - Temporary anchorage device usage: a survey among Swiss orthodontists.
AB  - BACKGROUND: The aim of the survey was to obtain information on the treatment plan
      preferences, mechanics and characteristics of temporary anchorage device (TAD)
      application using a single case presented to orthodontists in Switzerland.
      METHODS: A structured questionnaire to be completed by all study participants
      with case-specific (treatment plan including mechanics and TAD usage) and general
      questions (general fixed appliance and TAD usage as well as professional,
      educational and demographic questions) together with an orthodontic borderline
      case was utilised. The case was a female adult with dental Class II/2, deep bite
      and maxillary anterior crowing, who had been treated in childhood with extraction
      of four premolars and fixed appliance followed by wisdom tooth extraction.
      RESULTS: The response rate was 24.4% (108 out of 443). The majority (96.3%, 104)
      proposed comprehensive treatment, while 3.7% (4) planned only alignment of
      maxillary teeth. 8.3% (9) included a surgical approach in their treatment plan.
      An additional 0.9% (1) combined the surgical approach with Class II mechanics.
      75.1% (81) decided on distalization on the maxilla using TADs, 7.4% (8) planned
      various types of Class II appliances and 3.7% (4) combined distalization using
      TADs or headgear with Class II appliances and surgery. Palatal implants were the
      most popular choice (70.6%, 60), followed by mini-screws (22.4%, 19) and mini
      plates on the infrazygomatic crests (7.0%, 6). The preferred site of TAD
      insertion showed more variation in sagittal than in transversal dimension, and
      the median size of mini-screws used was 10.0-mm long (interquartile range (IQR)
      2.3 mm) and 2.0-mm wide (IQR 0.3 mm). CONCLUSIONS: Distalization against palatal
      implants and then distalization against mini-screws were the most popular
      treatment plans. Preferred site for TAD insertion varied depending on type and
      size but varied more widely in the sagittal than in the transversal dimension.

PMID- 24935645
TI  - Frequency of V1016I and F1534C mutations in the voltage-gated sodium channel gene
      in Aedes aegypti in Venezuela.
AB  - BACKGROUND: The V1016I and F1534C mutations in the voltage-gated sodium channel
      gene have been associated with resistance to pyrethroids and DDT in Aedes aegypti
      mosquitoes. A study was carried out to determine the frequency of I1016 and C1534
      by real-time PCR in five natural populations of Ae. aegypti in Venezuela during
      2008, 2010 and 2012, as well as in a strain selected with 0.14 ug of deltamethrin
      for 15 generations. RESULTS: In natural populations, frequencies of I1016 varied
      between 0.01 and 0.37, and frequencies of C1534 between 0.35 and 1.0. In the
      Pampanito strain, the frequency of I1016 increased from 0.02 in F1 up to 0.5 in
      F15 and from 0.35 up to fixation for C1534 after selection with deltamethrin.
      CONCLUSION: The results showed that C1534 frequencies are higher than I1016
      frequencies in natural populations of Ae. aegypti in Venezuela, and that
      deltamethrin selected the C1534 more rapidly than I1016.

PMID- 24935646
TI  - Prevalence of incidental thyroid nodules in ultrasound studies of dogs with
      hypercalcemia (2008-2013).
AB  - Ultrasound is commonly used to evaluate the cervical region in dogs with
      hypercalcemia due to suspected hyperparathyroidism. Incidental thyroid nodules
      may be detected during these studies, however little information has been
      published to guide clinical decision-making when this occurs. The purpose of this
      cross-sectional study was to determine the prevalence of incidental thyroid
      nodules in hypercalcemic dogs undergoing cervical ultrasound at our hospital
      during the period of 2008-2013. Dogs with a palpable neck mass were excluded.
      Cervical ultrasound images for each dog were retrieved and reviewed by a board
      certified veterinary radiologist who was unaware of patient outcome. Presence,
      number, and dimensions of thyroid nodules were recorded. Results of thyroid
      nodule aspirate, biopsy or necropsy were recorded from medical records when
      available. Ninety-one dogs met inclusion criteria. Of these, 14/91 (15%) dogs had
      at least one thyroid nodule. Mean (+/- standard deviation) thyroid gland nodule
      length, width, and height were 1.51 +/- 0.74, 0.96 +/- 0.73, and 0.75 +/- 0.36
      cm, respectively. A histologic diagnosis was available for the incidental thyroid
      lesions in eight dogs, including one dog with two nodules. Confirmed diagnoses
      for these nodules were thyroid cyst (3/9, 33%), thyroid adenoma (3/9, 33%),
      thyroid adenocarcinoma (2/9, 22%) and nodular hyperplasia (1/9, 11%). Findings
      indicated that incidental thyroid nodules may be present in hypercalcemic dogs
      with no palpable neck mass and no clinical signs of thyroid disease. Some of
      these nodules may be malignant and therefore a recommendation for cytology or
      biopsy may be justified. 

PMID- 24935647
TI  - A descriptive exploratory study of how admissions caused by medication-related
      harm are documented within inpatients' medical records.
AB  - BACKGROUND: Adverse drug reactions, poor patient adherence and errors, here
      collectively referred to as medication-related harm (MRH), cause around 2.7-8.0%
      of UK hospital admissions. Communication gaps between successive healthcare
      providers exist, but little is known about how MRH is recorded in inpatients'
      medical records. We describe the presence and quality of MRH documentation for
      patients admitted to a London teaching hospital due to MRH. Additionally, the
      international classification of disease 10th revision (ICD-10) codes attributed
      to confirmed MRH-related admissions were studied to explore appropriateness of
      their use to identify these patients. METHODS: Clinical pharmacists working on an
      admissions ward in a UK hospital identified patients admitted due to suspected
      MRH. Six different data sources in each patient's medical record, including the
      discharge summary, were subsequently examined for MRH-related information. Each
      data source was examined for statements describing the MRH: symptom and
      diagnosis, identification of the causative agent, and a statement of the action
      taken or considered. Statements were categorised as 'explicit' if unambiguous or
      'implicit' if open to interpretation. ICD-10 codes attributed to confirmed MRH
      cases were recorded. RESULTS: Eighty-four patients were identified over 141 data
      collection days; 75 met our inclusion criteria. MRH documentation was generally
      present (855 of 1307 statements were identified; 65%), and usually explicit (705
      of 855; 82%). The causative agent had the lowest proportion of explicit
      statements (139 of 201 statements were explicit; 69%). For two (3%) discharged
      patients, the causal agent was documented in their paper medical record but not
      on the discharge summary. Of 64 patients with a confirmed MRH diagnosis at
      discharge, only six (9%) had a MRH-related ICD-10 code. CONCLUSIONS: Availability
      of information in the paper medical record needs improving and communication of
      MRH-related information could be enhanced by using explicit statements and
      documenting reasons for changing medications. ICD-10 codes underestimate the true
      occurrence of MRH.

PMID- 24935648
TI  - A correlational study of suicidal ideation with psychological distress,
      depression, and demoralization in patients with cancer.
AB  - PURPOSE: This study aims to study the effects of depression and demoralization on
      suicidal ideation and to determine the feasibility of the Distress Thermometer as
      a screening tool for patients with cancer who experience depression and
      demoralization, and thus to establish a model screening process for suicide
      prevention. METHODS: Purposive sampling was used to invite inpatients and
      outpatients with lung cancer, leukemia, and lymphoma. Two hundred participants
      completed the questionnaire, which included the Distress Thermometer (DT),
      Patient Health Questionnaire-9 (PHQ-9), Demoralization Scale-Mandarin Version (DS
      MV), and Beck Scale for Suicide Ideation. All data obtained were analyzed using
      SPSS 18.0 and SAS 9.3. RESULTS: Tobit regression analysis showed that
      demoralization influenced suicidal ideation more than depression did (t = 2.84, p
      < 0.01). When PHQ-9 >= 10 and DS-MV >=42 were used as criteria for the DT,
      receiver operating characteristic analysis revealed that the AUC values were 0.77
      0.79, with optimal cutoff points for both of DT >=5; sensitivity 76.9 and 80.6 %,
      respectively; and specificity of 73.9 and 72.2 %, respectively. CONCLUSIONS:
      Demoralization had more influence on suicidal ideation than depression did.
      Therefore, attention should be paid to highly demoralized patients with cancer or
      high demoralization comorbid with depression for the purposes of suicide
      evaluation and prevention. The DT scale (with a cutoff of >=5 points) has
      discriminative ability as a screening tool for demoralization or depression and
      can also be used in clinical settings for the preliminary screening of patients
      with cancer and high suicide risk.

PMID- 24935649
TI  - Insomnia in adult survivors of childhood cancer: a report from project REACH.
AB  - PURPOSE: Insomnia is a common problem affecting cancer survivors even years after
      completion of therapy. Childhood cancer survivors may be at particular risk due
      to vulnerability to the effects of treatment and medical late effects which
      impact normal sleep development. Using an indicator of clinically significant
      insomnia (sleep efficiency), we examined a group of adult survivors of childhood
      cancer to (1) describe clinical insomnia rates, (2) identify physical and
      psychological correlates of insomnia, and (3) investigate the frequency with
      which sleep issues were evaluated during a cancer survivorship medical visit.
      METHODS: A total of 122 adult survivors of childhood cancer completed standard
      measures of sleep, psychological distress, and health-related quality of life.
      Medical records of the 75 survivors with a survivorship medical visit on the day
      of self-report measure completion were reviewed for documentation of sleep
      related issues. RESULTS: Twenty-eight percent of participants endorsed sleep
      efficiency below 85 %, indicating clinically significant insomnia. Insomnia was
      associated with poor physical health and anxiety but not with demographic or
      cancer treatment variables. Medical providers failed to document sleep in visit
      notes for 67 % of patients with self-reported insomnia. CONCLUSIONS: A
      significant proportion of adult survivors of childhood cancer report insomnia,
      which is associated with physical and psychological health. Few survivors with
      insomnia discuss this issue with oncology providers during survivorship care.
      There is a clear need to screen for insomnia in this population. Patients and
      providers should take greater responsibility for discussing sleep issues and
      seeking out proper treatment referrals when it is identified.

PMID- 24935651
TI  - Structure of a tractable stochastic mimic of soft particles.
AB  - The structure and assembly of soft particles is difficult to characterize because
      their interpenetrability allows them to be packed at ever higher density albeit
      with an increasing penalty in energy and/or pressure. Alternatively, the use of
      impenetrable particles (such as hard spheres) as a reference model for soft
      particles can fail because the packing densities are limited by the impossibility
      of complete space filling. We recently introduced the stochastic penetration
      algorithm (SPA) so as to allow for the computationally efficient integration of
      hard sphere models while including overlaps seen in soft interactions [Craven et
      al., J. Chem. Phys., 2013, 138, 244901]. Moving beyond the initial one
      dimensional case studied earlier, we now consider the spatial properties of
      systems of stochastically penetrable spheres in dimensions d<= 3 through the use
      of molecular dynamics simulations and analytic methods. The stochastic potential
      allows spheres to either interpenetrate with a probability delta or collide
      elastically otherwise. For delta > 0 the particles interpenetrate (overlap),
      reducing the effective volume occupied by the particles in the system. We find
      that the occupied volume can be accurately predicted using analytic expressions
      derived from mean field arguments for the particle overlap probabilities with the
      exception of an observed clustering regime. This anomalous clustering behavior
      occurs at high densities and small delta. We find that this regime is coincident
      with that observed in deterministic penetrable models. The behavior of the
      stochastic penetrable particles also indicates that soft particles would be
      characterizable through a single reduced parameter that captures their overlap
      probability. 

PMID- 24935650
TI  - A recombinant adenovirus-based vector elicits a specific humoral immune response
      against the V3 loop of HIV-1 gp120 in mice through the "Antigen Capsid
      Incorporation" strategy.
AB  - BACKGROUND: Due to potential advantages, human adenoviral vectors have been
      evaluated pre-clinically as recombinant vaccine vectors against several cancers
      and infectious diseases, including human immunodeficiency virus (HIV) infection.
      The V3 loop of HIV-1 glycoprotein 120 (gp120) contains important neutralizing
      epitopes and plays key roles in HIV entry and infectivity. METHODS: In order to
      investigate the humoral immune response development against portions of the V3
      loop, we sought to generate four versions of adenovirus (Ad)-based V3 vectors by
      incorporating four different antigen inserts into the hypervariable region 1
      (HVR1) of human adenovirus type 5 (hAd5) hexon. The strategy whereby antigens are
      incorporated within the adenovirus capsid is known as the "Antigen Capsid
      Incorporation" strategy. RESULTS: Of the four recombinant vectors, Ad-HVR1-lgs
      His6-V3 and Ad-HVR1-long-V3 had the capability to present heterologous antigens
      on capsid surface, while maintaining low viral particle to infectious particle
      (VP/IP) ratios. The VP/IP ratios indicated both high viability and stability of
      these two vectors, as well as the possibility that V3 epitopes on these two
      vectors could be presented to immune system. Furthermore, both Ad-HVR1-lgs-His6
      V3 and Ad-HVR1-long-V3 could, to some extent escape the neutralization by anti
      adenovirus polyclonal antibody (PAb), but rather not the immunity by anti-gp120
      (902) monoclonal antibody (MAb). The neutralization assay together with the whole
      virus enzyme-linked immunosorbent assay (ELISA) suggested that these two vectors
      could present V3 epitopes similar to the natural V3 presence in native HIV
      virions. However, subsequent mice immunizations clearly showed that only Ad-HVR1
      lgs-His6-V3 elicited strong humoral immune response against V3. Isotype ELISAs
      identified IgG2a and IgG2b as the dominant IgG isotypes, while IgG1 comprised the
      minority. CONCLUSIONS: Our findings demonstrated that human adenovirus (hAd)
      vectors which present HIV antigen via the "Antigen Capsid-Incorporation" strategy
      could successfully elicit antigen-specific humoral immune responses, which could
      potentially open an avenue for the development of Ad-based HIV V3 vaccines.

PMID- 24935652
TI  - Endobronchial ultrasound-guided transbronchial needle biopsy for the diagnosis of
      intrathoracic lymph node metastases from extrathoracic malignancies: a meta
      analysis and systematic review.
AB  - Intrathoracic lymph node metastases in patients with extrathoracic malignancies
      are a common clinical manifestation. Several studies evaluating intrathoracic
      lymph node metastases in patients with extrathoracic malignancy by using the
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have
      been reported. The objective of this meta-analysis is to investigate the
      diagnostic value of EBUS-TBNA for diagnosing intrathoracic lymph node metastases
      in patients with extrathoracic malignancies. We systematically searched Cochrane
      Library, Medline and Embase for relevant studies published prior to May 2013.
      Studies specifically designed to evaluate the diagnostic accuracy of EBUS-TBNA
      for intrathoracic lymph node metastases in patients with an extrathoracic
      malignancy were selected. Diagnostic accuracy meta-analysis was conducted by
      pooling estimates of sensitivity, specificity, negative likelihood ratio (NLR),
      positive likelihood ratio (PLR) and diagnostic odds ratios (DOR) derived from a
      summary receiver operating characteristic (SROC) analysis of the original
      studies. Six studies were included, which provided a dataset of 533 patients.
      EBUS-TBNA pooled estimates had 0.85 sensitivity (95% confidence interval (CI):
      0.80-0.89), 0.99 specificity (95% CI: 0.95-1.00), PLR 28.63 (95% CI: 11.51-71.22)
      and NLR 0.16 (95% CI: 0.12-0.21). The overall DOR was 179.77 (95% CI: 66.29
      487.50). The area under the SROC curve and the diagnostic accuracy were 0.9247
      and 0.8588, respectively. Evidence gathered from studies of moderate quality
      reveals a high degree of diagnostic accuracy of EBUS-TBNA for diagnosing
      intrathoracic lymph node metastases in patients with extrathoracic malignancies. 

PMID- 24935653
TI  - Rescue bedside laparotomy in the intensive care unit in patients too unstable for
      transport to the operating room.
AB  - INTRODUCTION: The prognoses of critically ill patients with a requirement for
      emergency laparotomy and severe respiratory and/or hemodynamic instability
      precluding transport to the operating room (OR) are often fatal without surgery.
      Attempting emergency surgery at the bedside might equally result in an adverse
      outcome. However, risk factors and predictors that could support clinical
      decision making have not been identified so far. This study describes the
      clinical characteristics, indicative pathophysiology and outcomes in patients
      undergoing resuscitative laparotomy in the intensive care unit (ICU). METHODS:
      This was a retrospective observational study of all critically ill adult patients
      undergoing resuscitative laparotomy in the ICUs of a German university hospital
      from January 2005 to July 2013. Clinical characteristics, risk factors, and
      treatments were compared between survivors and non-survivors. The primary
      endpoint was 28-day survival. RESULTS: A total of 41 patients with a median age
      of 64 (21 to 83) were included. The most frequent reasons for ICU admission were
      sepsis, pneumonia, and pancreatic surgery. All patients were mechanically
      ventilated, receiving vasopressors, and were in multiple organ failure. Twenty
      nine patients (70.7%) were on renal replacement therapy and two patients (4.9%)
      on extracorporeal membrane oxygenation. The main reasons for surgery were
      suspected intra-abdominal bleeding (39.0%), suspected intestinal ischemia (24.4%)
      or abdominal compartment syndrome (24.4%). Twenty-eight-day, ICU and hospital
      mortalities were 75.6%, 80.5%, and 82.9%, respectively. In six out of ten
      patients (60%) who survived surgery for more than 28 days, bedside laparotomy was
      rated as a life-saving procedure by an interdisciplinary group of the
      investigators. CONCLUSIONS: These findings suggest that in selected critically
      ill patients with a vital indication for emergency laparotomy and severe
      cardiopulmonary instability precluding transport to the OR, a bedside
      resuscitative laparotomy in the ICU can be considered as a rescue procedure, even
      though very high mortality is to be expected.

PMID- 24935656
TI  - Synthesis and luminescence resonance energy transfer based on noble metal
      nanoparticles and the NaYF4:Tb3+ shell.
AB  - A core-shell hybrid nanostructure was prepared by combining NaYF4 doped with the
      lanthanide dopant Tb(3+) as shell layer materials and noble metal nanoparticles
      (Au and Ag) as cores. For the core-shell system, the luminescence resonance
      energy transfer (LRET) was demonstrated, in which noble metal nanoparticles as
      fluorescence quenchers can absorb the emission energy of the alpha-NaYF4:Tb(3+)
      donor. The morphology, structure, composition and properties of the as-prepared
      samples were characterized by X-ray powder diffraction (XRD), transmission
      electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray
      photoelectron spectroscopy (XPS), UV-Vis absorption and photoluminescence (PL)
      spectroscopy, respectively. In the Au/Ag@NaYF4:Tb(3+) system, it is observed that
      the plasmonic absorption bands of gold or silver nanoparticles overlap with the
      emission bands of (5)D4->(7)F(j) (j = 6, 5) transition of the Tb(3+) ions, and
      the emission intensity of the (5)D4->(7)F5 transition is clearly attenuated. The
      photoluminescence decay curve measurements show that the lifetimes of the (5)D4
      >(7)F6 and (5)D4->(7)F5 transitions of Tb(3+) are slightly decreased in the
      presence of gold or silver cores. The quenching efficiency of the gold and silver
      nanoparticles implies that the efficiency of energy transfer is highly dependent
      on the extent of spectral overlap in the LRET system.

PMID- 24935657
TI  - Polyadenylation of Friend murine leukemia virus env-mRNA is affected by its
      splicing.
AB  - As splicing was previously found to be important for increasing Friend murine
      leukemia virus env-mRNA stability and translation, we investigated whether
      splicing of env-mRNA affected the poly(A) tail length using env expression
      vectors that yielded unspliced or spliced env-mRNA. Incomplete polyadenylation
      was detected in a fraction of the unspliced env-mRNA products in an env gene
      dependent manner, showing that splicing of Friend murine leukemia virus plays an
      important role in the efficiency of complete polyadenylation of env-mRNA. These
      results suggested that the promotion of complete polyadenylation of env-mRNA by
      splicing might partially explain up-regulation of Env protein expression as a
      result of splicing. 

PMID- 24935654
TI  - Progress and prospects for engineered T cell therapies.
AB  - Proof-of-concept studies have demonstrated the therapeutic potential of
      engineered T cells. Transfer of recombinant antigen-specific T cell receptors
      (TCR) and chimaeric antigen receptors (CARs) against tumour and viral antigens
      are under investigation by multiple approaches, including viral- and nonviral
      mediated gene transfer into both autologous and allogeneic T cell populations.
      There have been notable successes recently using viral vector-mediated transfer
      of CARs specific for B cell antigens, but also reports of anticipated and
      unanticipated complications in these and other studies. We review progress in
      this promising area of cellular therapy, and consider developments in antigen
      receptor therapies including the application of emerging gene-editing
      technologies. 

PMID- 24935658
TI  - Advancing the application of systems thinking in health: South African examples
      of a leadership of sensemaking for primary health care.
AB  - BACKGROUND: New forms of leadership are required to bring about the fundamental
      health system changes demanded by primary health care (PHC). Using theory about
      complex adaptive systems and policy implementation, this paper considers how
      actors' sensemaking and the exercise of discretionary power currently combine to
      challenge PHC re-orientation in the South African health system; and provides
      examples of leadership practices that promote sensemaking and power use in
      support of PHC. METHODS: The paper draws on observational, interview, and
      reflective data collected as part of the District Innovation and Action Learning
      for Health Systems Development (DIALHS) project being implemented in Cape Town,
      South Africa. Undertaken collaboratively between health managers and researchers,
      the project is implemented through cycles of action-learning, including
      systematic reflection and synthesis. It includes a particular focus on how local
      health managers can better support front line facility managers in strengthening
      PHC. RESULTS: The results illuminate how the collective understandings of staff
      working at the primary level - of their working environment and changes within it
      - act as a barrier to centrally-led initiatives to strengthen PHC. Staff often
      fail to take ownership of such initiatives and experience them as disempowering.
      Local area managers, located between the centre and the service frontline, have a
      vital role to play in providing a leadership of sensemaking to mediate these
      challenges. Founded on personal values, such leadership entails, for example,
      efforts to nurture PHC-aligned values and mind-sets among staff; build
      relationships and support the development of shared meanings about change; instil
      a culture of collective inquiry and mutual accountability; and role-model
      management practices, including using language to signal meaning. CONCLUSIONS:
      PHC will only become a lived reality within the South African health system when
      frontline staff are able to make sense of policy intentions and incorporate them
      into their everyday routines and practices. This requires a leadership of
      sensemaking that enables front line staff to exercise their collective
      discretionary power in strengthening PHC. We hope this theoretically-framed
      analysis of one set of experiences stimulates wider thinking about the leadership
      needed to sustain primary health care in other settings.

PMID- 24935659
TI  - Endogenous inhibition of hippocampal LTD and depotentiation by vasoactive
      intestinal peptide VPAC1 receptors.
AB  - Vasoactive intestinal peptide (VIP), an important modulator of hippocampal
      synaptic transmission, influences exploration and hippocampal-dependent learning
      in rodents. Homosynaptic long-term depression (LTD) and depotentiation are two
      plasticity phenomena implicated in learning of behavior flexibility and spatial
      novelty detection. In this study, we investigated the influence of endogenous VIP
      on LTD and depotentiation induced by low-frequency stimulation (1 Hz, 900 pulses)
      of the hippocampal CA1 area in vitro in juvenile and young adult rats,
      respectively. LTD and depotentiation were enhanced by the VIP receptor antagonist
      Ac-Tyr(1) , D-Phe(2) GRF (1-29), and the selective VPAC1 receptor antagonist, PG
      97-269, but not the selective VPAC2 receptor antagonist, PG 99-465. This action
      was mimicked by an anti-VIP antibody, suggesting that VIP, and not pituitary
      adenylate cyclase-activating polypeptide (PACAP), is the endogenous mediator of
      these effects. Selective inhibition of PAC1 receptors with PACAP (6-38) enhanced
      depotentiation, but not LTD. VPAC1 receptor blockade also revealed LTD in young
      adult rats, an effect abolished by the GABAA antagonist bicuculline, evidencing
      an involvement of GABAergic transmission. We conclude that inhibition of LTD and
      depotentiation by endogenous VIP occurs through VPAC1 receptor-mediated
      mechanisms and suggest that disinhibition of pyramidal cell dendrites is the most
      likely physiological mechanism underlying this effect. As such, VPAC1 receptor
      ligands may be considered promising pharmacological targets for treatment of
      cognitive dysfunction in diseases involving altered GABAergic circuits and
      pathological saturation of LTP/LTD like Down's syndrome and temporal lobe
      epilepsy.

PMID- 24935660
TI  - Simple and comminuted displaced olecranon fractures: a clinical comparison
      between tension band wiring and plate fixation techniques.
AB  - INTRODUCTION: The purpose of this retrospective study is to compare the clinical,
      functional outcome and complications occurrence between tension band wiring (TBW)
      and plate fixation both for simple and comminuted displaced olecranon fractures.
      MATERIALS AND METHODS: Between January 2005 and June 2012 (minimum 1-year follow
      up), 78 consecutive patients with Mayo type IIA and IIB fractures were treated
      with the following methods: tension band wire or plate and screws fixation. The
      primary outcome of this study was the functional outcome, assessed by the
      following self-administered evaluation scales: the disabilities of the arm,
      shoulder and hand, and the Mayo Elbow Performance Score. Secondary outcome
      measures included the assessment of pain level, analysis of passive range of
      motion, and the occurrence of any early or late complications. RESULTS: Comparing
      the clinical results between the two groups, at mean 33 months follow-up, no
      significant differences in the functional and clinical outcome were observed.
      Complications were reported in 48 and 17 % of cases, following TBW and plate
      fixation in patients treated for type IIA fractures, and similarly in 40 and 23 %
      of cases in type IIB fractures, respectively. Hardware removal was more
      frequently performed in TBW group: 38 versus 17 % for type IIA fractures and 20
      versus 6 % for type IIB fractures. CONCLUSIONS: The findings of this study
      indicate that both with the use of TBW and plate fixation excellent/good clinical
      outcomes with minimal loss of physical capacity, little pain and disability can
      be obtained in the majority of patients with simple and comminuted displaced
      olecranon fractures. Hardware removal was most frequently observed after TBW.

PMID- 24935661
TI  - Grip force monitoring on the hand: Manugraphy system versus Jamar dynamometer.
AB  - INTRODUCTION: For clinical grip force assessment, the Jamar dynamometer is a wide
      accepted tool. Users have to be aware that this method does not represent all
      grip efforts applied. The Manugraphy system is a tool that measure total grip
      force as well as identify load distribution patterns of the hand while gripping
      cylinders wrapped with calibrated capacitive matrix sensor mats. The aim of this
      study was to validate an assessment setting of the Manugraphy system for clinical
      use. Further, the relationship and difference between the Manugraphy system and
      the Jamar dynamometer were investigated. MATERIALS AND METHODS: At two study
      centers, 152 healthy volunteers performed grip force tests with a digital Jamar
      dynamometer using handle positions 3 and 4 and the novel((r)) Manugraphy system
      using two cylinders with circumferences of 150 and 200 mm. The subjects performed
      grip force testing with both devices on three different days. The intra- and
      inter-day variability for both methods was evaluated. To compare the values of
      both systems, the Spearman correlation coefficient was calculated. RESULTS: The
      force values, as measured by the sensor matrix, were higher than those of the
      Jamar dynamometer. Analyses showed significant positive correlations between
      values obtained by the two measurement methods (p < 0.001). There was no
      significant inter-day variation for the 200-mm cylinder of the Manugraphy system.
      For the 150-mm cylinder, a significant variation was observed at center B, but
      not at A. Nevertheless, the fluctuation of the grip force values obtained with
      the Manugraphy system was equal or better than those obtained with the Jamar
      dynamometer. CONCLUSIONS: The force values, obtained using the two systems, have
      a high correlation but are not directly comparable. Both systems allow valid and
      constant grip force measurement. As the sensor mat detects all forces applied
      perpendicularly to the cylinder surface, it characterizes grip force better than
      the Jamar dynamometer. In addition, information about load distribution of the
      hand is gained.

PMID- 24935662
TI  - Comparison of outside-in and inside-out technique for tibial fixation of a soft
      tissue graft in ACL reconstruction using the Shim technique.
AB  - INTRODUCTION: The aim of this study was to compare the biomechanical properties
      of tibial fixation of a free tendon graft in ACL reconstruction using the Shim, a
      new wedge-shaped implant, in an outside-in technique to fixation by the Shim used
      in an inside-out technique and fixation by interference screw in a porcine model.
      MATERIALS AND METHODS: Porcine tibia and flexor tendons were used. In Group 1,
      the Shim was applied outside-in. In Group 2, the Shim was inserted inside-out. In
      the Group 3, an 8-mm interference screw was used. Ten specimens were tested in
      each group. Load-to-failure, elongation, stiffness and failure mode were
      recorded. Cyclic loading was performed between 5 and 250 N for 1,000 cycles,
      followed by a load to failure testing. RESULTS: Mean maximum load-to-failure was
      629.53 N in Group 1,648.54 N in Group 2 and 749.53 N in Group 3. There was no
      significant difference between the groups. Stiffness varied between 127.34 N/mm
      in Group 1, 151.27 N/mm in Group 2 and 182.25 N/mm in Group 3. No significant
      differences were found between outside-in Shim and interference screw fixation.
      No significant difference was found for elongation among the three groups. The
      main failure mode was a rupture of the tendon in the IFS group and a slippage of
      either the implant or the tendon in both groups using the Shim. CONCLUSIONS: As
      no statistically significant difference could be seen concerning load to failure,
      stiffness and elongation between the inside-out and the outside-in techniques,
      the Shim can be used for tibial fixation in an outside-in or inside-out technique
      depending on the preference of the surgeon. To prevent slippage of the graft a
      hybrid fixation should be considered.

PMID- 24935663
TI  - Results of operative treatment for recalcitrant retrocalcaneal bursitis and
      midportion Achilles tendinopathy in athletes.
AB  - BACKGROUND: The results of operative treatment for recalcitrant midportion
      Achilles tendinopathy and recalcitrant retrocalcaneal bursitis were evaluated
      using the patient administered, disease specific, and validated VISA-A-G
      questionnaire. METHODS: A cohort of 89 patients was prospectively followed. These
      patients underwent operations for sport induced midportion Achilles tendinopathy
      (39 procedures) or retrocalcaneal bursitis (55 procedures). Depending on the
      individual intraoperative findings the patients of either disease were treated
      with two respective operative modifications (tendon repair or no tendon repair).
      Preoperative and follow-up status (3, 6, and 12 months) were investigated using
      the VISA-A-G questionnaire. RESULTS: Preoperatively, the four groups scored from
      37.0 +/- 17.6 to 45.9 +/- 15.2 (p = 0.376-0.993) on the VISA-A-G questionnaire.
      Six and 12 months postoperatively, the VISA-A-G scores improved significantly (p
      < 0.001). Twelve months postoperatively, the groups' scores were not different (p
      = 0.100-0.952) and ranged from 80.8 +/- 17.9 to 90.3 +/- 10.6. CONCLUSION:
      Retrocalcaneal bursitis and midportion Achilles tendinopathy responded equally
      well to operative treatment. When repaired, additional tendon lesions did not
      influence this result. We demand to differentiate not only between midportion
      Achilles tendinopathy and retrocalcaneal bursitis but also to identify additional
      Achilles tendon lesions to specifically address these lesions during operative
      procedures.

PMID- 24935665
TI  - Ecological dynamics of continuous and categorical decision-making: the regatta
      start in sailing.
AB  - Ecological dynamics of decision-making in the sport of sailing exemplifies
      emergent, conditionally coupled, co-adaptive behaviours. In this study,
      observation of the coupling dynamics of paired boats during competitive sailing
      showed that decision-making can be modelled as a self-sustained, co-adapting
      system of informationally coupled oscillators (boats). Bytracing the spatial
      temporal displacements of the boats, time series analyses (autocorrelations,
      periodograms and running correlations) revealed that trajectories of match racing
      boats are coupled more than 88% of the time during a pre-start race, via
      continuous, competing co-adaptions between boats. Results showed that both the
      continuously selected trajectories of the sailors (12 years of age) and their
      categorical starting point locations were examples of emergent decisions. In this
      dynamical conception of decision-making behaviours, strategic positioning
      (categorical) and continuous displacement of a boat over the course in match-race
      sailing emerged as a function of interacting task, personal and environmental
      constraints. Results suggest how key interacting constraints could be manipulated
      in practice to enhance sailors' perceptual attunement to them in competition. 

PMID- 24935667
TI  - The dog as a genetic model for immunoglobulin A (IgA) deficiency: identification
      of several breeds with low serum IgA concentrations.
AB  - Immunoglobulin A (IgA) serves as the basis of the secretory immune system by
      protecting the lining of mucosal sites from pathogens. In both humans and dogs,
      IgA deficiency (IgAD) is associated with recurrent infections of mucosal sites
      and immune-mediated diseases. Low concentrations of serum IgA have previously
      been reported to occur in a number of dog breeds but no generally accepted cut
      off value has been established for canine IgAD. The current study represents the
      largest screening to date of IgA in dogs in terms of both number of dogs (n=1267)
      and number of breeds studied (n=22). Serum IgA concentrations were quantified by
      using capture ELISA and were found to vary widely between breeds. We also found
      IgA to be positively correlated with age (p<0.0001). Apart from the two breeds
      previously reported as predisposed to low IgA (Shar-Pei and German shepherd), we
      identified six additional breeds in which >= 10% of all tested dogs had very low
      (<0.07 g/l) IgA concentrations (Hovawart, Norwegian elkhound, Nova Scotia duck
      tolling retriever, Bullterrier, Golden retriever and Labrador retriever). In
      addition, we discovered low IgA concentrations to be significantly associated
      with canine atopic dermatitis (CAD, p<0.0001) and pancreatic acinar atrophy (PAA,
      p=0.04) in German shepherds.

PMID- 24935666
TI  - Occupational exposure to extremely low-frequency magnetic fields and brain tumor
      risks in the INTEROCC study.
AB  - BACKGROUND: Occupational exposure to extremely low-frequency magnetic fields
      (ELF) is a suspected risk factor for brain tumors, however the literature is
      inconsistent. Few studies have assessed whether ELF in different time windows of
      exposure may be associated with specific histologic types of brain tumors. This
      study examines the association between ELF and brain tumors in the large-scale
      INTEROCC study. METHODS: Cases of adult primary glioma and meningioma were
      recruited in seven countries (Australia, Canada, France, Germany, Israel, New
      Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday
      ELF exposure based on a job exposure matrix were assigned. Estimates of
      cumulative exposure, average exposure, maximum exposure, and exposure duration
      were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the
      diagnosis/reference date. RESULTS: There were 3,761 included brain tumor cases
      (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no
      association between lifetime cumulative ELF exposure and glioma or meningioma
      risk. However, there were positive associations between cumulative ELF 1 to 4
      years before the diagnosis/reference date and glioma [odds ratio (OR) >= 90th
      percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36-2.07;
      PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR >=
      90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97-1.57; PLinear trend =
      0.02). CONCLUSIONS: Results showed positive associations between ELF in the
      recent past and glioma. IMPACT: Occupational ELF exposure may play a role in the
      later stages (promotion and progression) of brain tumorigenesis.

PMID- 24935668
TI  - Cell growth and resistance of Lactococcus lactis subsp. lactis TOMSC161 following
      freezing, drying and freeze-dried storage are differentially affected by
      fermentation conditions.
AB  - AIMS: To investigate the effects of fermentation parameters on the cell growth
      and on the resistance to each step of the freeze-drying process of Lactococcus
      lactis subsp. lactis TOMSC161, a natural cheese isolate, using a response surface
      methodology. METHODS AND RESULTS: Cells were cultivated at different temperatures
      (22, 30 and 38 degrees C) and pH (5.6, 6.2 and 6.8) and were harvested at
      different growth phases (0, 3 and 6 h of stationary phase). Cultivability and
      acidification activity losses of Lc. lactis were quantified after freezing,
      drying, 1 and 3 months of storage at 4 and 25 degrees C. Lactococcus lactis was
      not damaged by freezing but was sensitive to drying and to ambient temperature
      storage. Moreover, the fermentation temperature and the harvesting time
      influenced the drying resistance of Lc. lactis. CONCLUSIONS: Lactococcus lactis
      cells grown in a whey-based medium at 32 degrees C, pH 6.2 and harvested at late
      stationary phase exhibited both an optimal growth and the highest resistance to
      freeze-drying and storage. SIGNIFICANCE AND IMPACT OF THE STUDY: A better insight
      on the individual and interaction effects of fermentation parameters made it
      possible the freeze-drying and storage preservation of a sensitive strain of
      technological interest. Evidence on the particularly damaging effect of the
      drying step and the high-temperature storage is presented.

PMID- 24935669
TI  - Incidence of oral cancer in Western Australia (1982-2009): Trends and regional
      variations.
AB  - AIM: Oral cancer remains a significant issue for many communities of the world.
      In Australia, there are approximately 2000 new diagnoses each year, and the rates
      are growing. The divide between city and rural, rich and poor, is, in many
      countries, found to be linked to the incidence of oral cancer. The aim of this
      study was to determine the trends in the incidence of oropharyngeal cancer
      (specifically cancer of the parotid and major salivary glands, pharynx, and
      tongue) in Western Australia over a 27-year period, from 1982 to 2009, and
      determine the geographic distribution of incidence within the state. METHODS: The
      de-identified data were provided by the Western Australian Cancer Registry, as
      oral cancer is a notifiable condition in Australia. RESULTS: There were a total
      of 2801 cases reported with pharynx, tongue, major salivary glands and parotid
      cancers over a 27-year period: 73.2 percent were male and 26.8 percent were
      female. The age-standardized incidence rate was 67.4 per 100 000 persons per
      annum for pharyngeal cancer, 54.1 for tongue cancer, 22.2 for parotid gland
      cancer and 5.5 for major salivary gland cancer. The age-standardized rates for
      pharyngeal and tongue cancer (but not parotid) were higher in country areas of
      Western Australia than in the metropolitan areas. The burden of some site
      specific oral cancers is continuing to rise. An increasing trend with older age
      is also consistent throughout the study period. CONCLUSION: This study finds that
      the incidence of oral cancers in Western Australia is not inconsistent with other
      parts of Australia and fundamentally shows there is a rural-urban difference for
      oral cancer.

PMID- 24935670
TI  - A new approach for efficient genotype imputation using information from
      relatives.
AB  - BACKGROUND: Genotype imputation can help reduce genotyping costs particularly for
      implementation of genomic selection. In applications entailing large populations,
      recovering the genotypes of untyped loci using information from reference
      individuals that were genotyped with a higher density panel is computationally
      challenging. Popular imputation methods are based upon the Hidden Markov model
      and have computational constraints due to an intensive sampling process. A fast,
      deterministic approach, which makes use of both family and population
      information, is presented here. All individuals are related and, therefore, share
      haplotypes which may differ in length and frequency based on their relationships.
      The method starts with family imputation if pedigree information is available,
      and then exploits close relationships by searching for long haplotype matches in
      the reference group using overlapping sliding windows. The search continues as
      the window size is shrunk in each chromosome sweep in order to capture more
      distant relationships. RESULTS: The proposed method gave higher or similar
      imputation accuracy than Beagle and Impute2 in cattle data sets when all
      available information was used. When close relatives of target individuals were
      present in the reference group, the method resulted in higher accuracy compared
      to the other two methods even when the pedigree was not used. Rare variants were
      also imputed with higher accuracy. Finally, computing requirements were
      considerably lower than those of Beagle and Impute2. The presented method took 28
      minutes to impute from 6 k to 50 k genotypes for 2,000 individuals with a
      reference size of 64,429 individuals. CONCLUSIONS: The proposed method
      efficiently makes use of information from close and distant relatives for
      accurate genotype imputation. In addition to its high imputation accuracy, the
      method is fast, owing to its deterministic nature and, therefore, it can easily
      be used in large data sets where the use of other methods is impractical.

PMID- 24935671
TI  - Photoperiodic co-regulation of kisseptin, neurokinin B and dynorphin in the
      hypothalamus of a seasonal rodent.
AB  - In many species, sexual activity varies on a seasonal basis. Kisspeptin (Kp), a
      hypothalamic neuropeptide acting as a strong activator of gonadotrophin-releasing
      hormone neurones, plays a critical role in this adaptive process. Recent studies
      report that two other neuropeptides, namely neurokinin B (NKB) and dynorphin
      (DYN), are co-expressed with Kp (and therefore termed KNDy neurones) in the
      arcuate nucleus and that these peptides are also considered to influence GnRH
      secretion. The present study aimed to establish whether hypothalamic NKB and DYN
      expression is photoperiod-dependent in a seasonal rodent, the Syrian hamster,
      which exhibits robust seasonal rhythms in reproductive activity. The majority of
      Kp neurones in the arcuate nucleus co-express NKB and DYN and the expression of
      all three peptides is decreased under a short (compared to long) photoperiod,
      leading to a 60% decrease in the number of KNDy neurones under photo-inhibitory
      conditions. In seasonal rodents, RFamide-related peptide (RFRP) neurones of the
      dorsomedial hypothalamus are also critical for seasonal reproduction.
      Interestingly, NKB and DYN are also expressed in the dorsomedial hypothalamus but
      do not co-localise with RFRP-immunoreactive neurones, and the expression of both
      NKB and DYN is higher under a short photoperiod, which is opposite to the short
      day inhibition of RFRP expression. In conclusion, the present study shows that
      NKB and DYN display different photoperiodic variations in the Syrian hamster
      hypothalamus. In the arcuate nucleus, NKB and DYN, together with Kp, are down
      regulated under a short photoperiod, whereas, in the dorsomedial hypothalamus,
      NKB and DYN are up-regulated under a short photoperiod. 

PMID- 24935672
TI  - Meta-analysis to assess the quality of international normalized ratio control and
      associated outcomes in venous thromboembolism patients.
AB  - INTRODUCTION: Patients with venous thromboembolism (VTE) frequently require
      vitamin K antagonists (VKAs) to prevent recurrent events, but their use increases
      hemorrhage risk. We performed a meta-analysis to assess the quality of
      international normalized ratio (INR) control, identify study-level predictors of
      poor control and to examine the relationship between INR control and adverse
      outcomes in VTE patients. MATERIALS AND METHODS: We searched bibliographic
      databases (1990-June 2013) for studies of VTE patients receiving adjusted-dose
      VKAs that reported time in range (2.0-3.0) or proportion of INRs in range and/or
      reported INR measurements coinciding with thromboembolic or hemorrhagic events.
      Meta-analysis and meta-regression analysis was performed. RESULTS: Upon meta
      analysis, studies found 59% (95%CI: 54-64%) of INRs measured and 61% (95%CI: 59
      63%) of the time patients were treated were spent outside the target range of 2.0
      3.0; with a tendency for under- versus over-anticoagulation. Moreover, this poor
      INR control resulted in a greater chance of recurrent VTE (beta-coefficient=
      0.46, p=0.01) and major bleeding (beta-coefficient=-0.30, p=0.02). Patients with
      an INR<2.0 made up 58% (95%CI: 39-77%) of VTE cases, while those with an INR>3.0
      made up 48% (95%CI: 34-61%) of major hemorrhage cases. Upon meta-regression,
      being VKA-naive (-14%, p=0.04) and treated in the community (-7%, p<0.001) were
      associated with less time in range, while being treated in Europe/United Kingdom
      (compared to North America) was associated with (11%, p=0.003) greater time.
      CONCLUSIONS: Strategies to improve INR control or alternative anticoagulants,
      including the newer oral agents, should be widely implemented in VTE patients to
      reduce the rate of recurrent events and bleeding.

PMID- 24935673
TI  - The knee in severe haemophilia with special emphasis on surgical/invasive
      procedures.
AB  - Close collaboration between haematologists, orthopaedic surgeons, rehabilitation
      physicians, pediatricians, pharmacist, radiologist, pain specialist,
      psychologists, physiotherapists and nurses is essential for the proper handling
      of knee problems in haemophiliac patients. The ideal scenario would be for the
      primary prophylaxis (prevention of the disease) to prevent major degenerative
      changes that we still see so frequently in this type of patients. Until we
      achieve this we will continue having to perform multiple invasive orthopaedic
      procedures, such as articular punctures (joint aspiration) to drain
      haemarthrosis, radiosynovectomies, arthroscopic synovectomies, tendon
      lenghtenings, realignment osteotomies and total knee replacements (primary and
      revision) on the knees of people with haemophilia. As a result of this, we will
      improve the quality of life of haemophiliac patients with orthopaedic knee
      problems. The rate of potential complications following knee orthopaedic
      procedures, especially in patients with inhibitors, must not be underestimated. 

PMID- 24935674
TI  - Verification of the guidelines for lupus anticoagulant detection: usefulness of
      index for circulating anticoagulant in APTT mixing test.
AB  - INTRODUCTION: Lupus anticoagulant (LA) is an antibody that interferes with one or
      more in vitro coagulation reactions, which are dependent on interactions with
      protein-phospholipid complexes. For LA diagnosis, a mixing test is considered
      useful for differentiating the inhibitor from a factor deficiency. However, the
      usefulness and the index of circulating anticoagulant (ICA) in a mixing test with
      activated partial thromboplastin time (APTT) has not been adequately
      investigated, and there is scant information regarding the effects of warfarin,
      heparin, and hemophilia plasma on ICA. We evaluated the usefulness of ICA by
      investigating the correlation of that index with international normalized ratio
      (INR), heparin concentration, and factor VIII activity in hemophilia patients.
      MATERIALS AND METHODS: We examined samples from 28 patients positive for LA, 23
      receiving warfarin, 19 receiving unfractionated heparin, and 29 with hemophilia
      A, as well as 61 normal samples. APTT-SLA, Actin FSL, APTT-SP, and PTT-LA were
      used as reagents in this study. RESULTS: The correlation coefficient values
      between ICA and INR, heparin concentration, and factor VIII activity ranged from
      0.031-0.342, 0.764-0.843, and 0.564-0.754, respectively, with the 4 reagents. The
      ICA values for the LA-positive samples were significantly higher than for the
      normal, warfarin, heparin, and hemophilia samples with all APTT reagents. Samples
      with a high heparin concentration above approximately 0.5U/ml showed ICA values
      greater than 15. CONCLUSION: ICA was able to distinguish LA-positive samples from
      the normal, warfarin, and hemophilia samples, but not heparin samples. ICA
      calculated from APTT clotting time is useful for LA diagnosis.

PMID- 24935675
TI  - Cost-effectiveness of apixaban versus warfarin and aspirin in Sweden for stroke
      prevention in patients with atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF), one of the major risk factors for stroke,
      imposing a substantial burden to the Swedish health care system. Apixaban has
      demonstrated superiority to warfarin and aspirin in stroke prevention amongst
      patients with AF in two large randomised clinical trials. The aim of this study
      was to assess the economic implications of apixaban against warfarin and aspirin
      in these patients from a Swedish societal perspective. MATERIALS AND METHODS: A
      Markov cohort model was constructed to characterise the consequences of
      anticoagulant treatment with regards to thromboembolic and bleeding events, as
      well as the associated health care costs, life-years and quality-adjusted life
      years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin.
      Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban
      relative to warfarin (among patients suitable for warfarin treatment) and aspirin
      (among patients unsuitable for warfarin treatment) were calculated. Costs (in
      2011 SEKs) and QALYs were discounted at 3% per annum. RESULTS: The model
      estimated the ICER of apixaban versus warfarin amongst patients who are suitable
      for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus
      aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY
      gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal
      treatment option compared with warfarin and aspirin, when the willingness-to-pay
      is above SEK 35,000 and SEK 45,000 per QALY, respectively. CONCLUSIONS: Apixaban
      was found to be a cost-effective alternative to warfarin and aspirin for stroke
      prevention in patients with AF in Sweden.

PMID- 24935677
TI  - Methionine restriction restores a younger metabolic phenotype in adult mice with
      alterations in fibroblast growth factor 21.
AB  - Methionine restriction (MR) decreases body weight and adiposity and improves
      glucose homeostasis in rodents. Similar to caloric restriction, MR extends
      lifespan, but is accompanied by increased food intake and energy expenditure.
      Most studies have examined MR in young animals; therefore, the aim of this study
      was to investigate the ability of MR to reverse age-induced obesity and insulin
      resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed
      MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h.
      Food intake and whole-body physiology were assessed and serum/tissues analyzed
      biochemically. Methionine restriction in 12-month-old mice completely reversed
      age-induced alterations in body weight, adiposity, physical activity, and glucose
      tolerance to the levels measured in healthy 2-month-old control-fed mice. This
      was despite a significant increase in food intake in 12-month-old MR-fed mice.
      Methionine restriction decreased hepatic lipogenic gene expression and caused a
      remodeling of lipid metabolism in white adipose tissue, alongside increased
      insulin-induced phosphorylation of the insulin receptor (IR) and Akt in
      peripheral tissues. Mice restricted of methionine exhibited increased circulating
      and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and
      expression of ATF4, with a concomitant decrease in IRE1alpha phosphorylation.
      Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and
      insulin signaling and improved whole-body glucose homeostasis without affecting
      body weight. Our findings suggest that MR feeding can reverse the negative
      effects of aging on body mass, adiposity, and insulin resistance through an FGF21
      mechanism. These findings implicate MR dietary intervention as a viable therapy
      for age-induced metabolic syndrome in adult humans.

PMID- 24935676
TI  - Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and
      repigmentation.
AB  - To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2
      mice, expressing both a human-derived, tyrosinase-reactive T-cell receptor on T
      cells and the matching HLA-A2 transgene, were crossed to keratin 14-promoter
      driven, stem cell factor transgenic (K14-SCF) mice with intra-epidermal
      melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes
      symmetrical and sharply demarcated patches of graying hair. Whereas the SCF
      transgene alone dictates a greater retinoic acid receptor-related orphan receptor
      gamma (RORgammat)(+) T-cell compartment, these cells displayed markedly increased
      IL-17 expression within Vitesse mice. Similar to patient skin, regulatory T cells
      were less abundant compared with K14-SCF mice, with the exception of gradually
      appearing patches of repigmenting skin. The subtle repigmentation observed likely
      reflects resilient melanocytes that coexist with skin-infiltrating, melanocyte
      reactive T cells. Similar repigmenting lesions were found in a different TCR
      transgenic model of vitiligo developed on an SCF transgenic background,
      supporting a role for SCF in repigmentation. 

PMID- 24935678
TI  - How do psychiatrists address delusions in first meetings in acute care? A
      qualitative study.
AB  - BACKGROUND: Communicating about delusions can be challenging, particularly when a
      therapeutic relationship needs to be established in acute care. So far, no
      systematic research has explored how psychiatrists address patients' delusional
      beliefs in first meetings in acute care. The aim of this study was to describe
      how psychiatrists address patients' delusional experiences in acute in-patient
      care. METHODS: First meetings between five psychiatrists and 14 patients in acute
      care were audio-recorded and analysed using thematic content analysis. RESULTS:
      296 psychiatrist statements about delusions were identified and coded. Three
      commonly used approaches (with a total of 6 subthemes) were identified. The most
      common approaches were eliciting the content (1 subtheme: eliciting content and
      evidence) and understanding the impact (3 subthemes: identifying emotions,
      exploring links with dysfunctional behaviour and discussing reasons for hospital
      admission) while questioning the validity of the beliefs (2 subthemes:
      challenging content and exploring alternative explanations) was less common. The
      last approach sometimes put patients in a defensive position. CONCLUSIONS:
      Psychiatrists commonly use three approaches to address patients' delusions in the
      first meeting in acute in-patient care. Questioning the patients' beliefs can
      lead to disagreement which might hinder establishing a positive therapeutic
      relationship. Future research should explore the impact of such an approach on
      outcomes and specify to what extent questioning the validity of delusional
      beliefs is appropriate in the first meeting.

PMID- 24935679
TI  - Dual cross-linking ribonucleoprotein immunoprecipitation assay.
AB  - Ribonucleoprotein immunoprecipitation (RIP) is an antibody-based method to detect
      RNA-protein interactions in situ. In the assay, UV cross-linking is commonly used
      to preserve RNA-protein interactions for subsequent target identification. UV
      light is a zero-length cross linker and thus identifies proteins directly bound
      to RNAs. Here, we describe a dual cross-linking RIP method that involves
      sequential protein-protein cross-linking step with a protein-protein cross
      linker, followed by protein-RNA fixation by UV irradiation. In this way, proteins
      that indirectly bound to RNA can be analyzed. 

PMID- 24935680
TI  - [Ischemia-reperfusion injury after lung transplantation].
AB  - Lung ischemia-reperfusion is characterized by diffuse alveolar damage arising
      from the first hours after transplantation. The first etiology of the primary
      graft dysfunction in lung is ischemia-reperfusion. It is burdened by an important
      morbi-mortality. Lung ischemia-reperfusion increases the oxidative stress,
      inactivates the sodium pump, increases the intracellular calcium, leads to
      cellular death and the liberation of pro-inflammatory mediators. Researches
      relative to the reduction of the lung ischemia-reperfusion injuries are numerous
      but few of them found a place in common clinical practice, because of an
      insufficient level of proofs. Ex vivolung evaluation is a suitable technique in
      order to evaluate therapeutics supposed to limit lung ischemia-reperfusion
      injuries. 

PMID- 24935681
TI  - [What future for carotid stenosis management?].
AB  - Surgery remains the first choice intervention in patients with severe symptomatic
      carotid stenosis. Stenting is associated with a higher periprocedural risk of
      stroke compared with surgery. This excess risk of stroke with stenting mainly
      concerns patients older than 70years, whereas the risk seems to be similar in
      patients younger than 70years. After the procedural period, both surgery and
      stenting appear to be as effective to prevent stroke. Studies are ongoing to
      identify patients who benefit most from carotid surgery or stenting. In patients
      with asymptomatic carotid stenosis, the risk of first ipsilateral stroke on
      medical treatment alone is currently lower (less than 1% per year) than it was at
      the time of randomized clinical trials, which showed a modest benefit of carotid
      surgery over medical treatment alone. Randomized trials are ongoing to re-assess
      the benefit of carotid revascularization in patients with asymptomatic carotid
      stenosis. Pending results of these trials, carotid revascularization should
      remain a case by case decision, taking into account the individual risk of
      ispilateral stroke, the risk of revascularization, the predicted life expectancy,
      and patient's preferences. 

PMID- 24935682
TI  - [Cystic lymphangioma of the ascending mesocolon].

PMID- 24935683
TI  - [Bipolar disorder in children and adolescents: a difficult diagnosis].
AB  - Bipolar disorder (BD) is a severe mental condition with neurodevelopmental
      features that clinically results in pathological fluctuations of mood. Whereas it
      was classically or traditionally considered as an adult-onset disorder, recent
      findings suggest that BD may occur very early in the life course, thus,
      determining what is now called Juvenile bipolar disorder (JBD). One of the
      reasons for which JBD has been so difficult to identify is that JBD primary
      symptoms vary much from the typical adulthood BD clinical expression. Euphoric
      mood is rare in JBD, while irritability mood, aggressive temper, mixed manic
      state onset, rapid cycling, anger outbursts and chronic course of symptoms are
      much more frequent. This specific clinical presentation makes JBD difficult to
      differentiate from other diagnoses related to pathological externalizing
      behaviours, including conduct disorder, oppositional provocative disorder, and
      attention deficit-hyperactivity disorder.

PMID- 24935684
TI  - Splenomegaly in hematological malignancies and portal hypertension.

PMID- 24935685
TI  - [Patient education of depression in primary care].

PMID- 24935687
TI  - Occurrence of Anisakis simplex sensu stricto in imported Atlantic mackerel
      (Scomber scombrus) represents a risk for Turkish consumers.
AB  - Anisakid larvae are a prevalent food-borne pathogen that has been found in
      numerous fish species destined for human consumption. The accidental consumption
      of infected raw or poorly cooked fish may cause gastroenteric diseases and
      allergies in humans. In spite of the fact that thorough cooking or freezing kills
      Anisakis worms, this method does not destroy their allergenic capacity. The
      presence of A. simplex (s.s.) in seafood products may present a health risk for
      consumers. In Turkey, Atlantic mackerels are marketed as frozen and mainly
      imported from Norway. The aim of this study was to identify the Anisakis species
      found in deep-frozen whole Atlantic mackerel (Scomber scombrus) destined for
      human consumption in fish markets that imported fish from Norway to Turkey. All
      Anisakis larvae isolated from imported Atlantic mackerel were identified via
      morphology as third larvae of Anisakis Type I. The ITS region (ITS-1, 5.8S
      subunit, ITS-2) was amplified and digested with the restriction enzymes Hinf I
      and Hha I. Larvae of the genus Anisakis were identified via PCR-RFLP as belonging
      to Anisakis simplex (s.s.), and this was confirmed by sequencing the cox2 gene.
      The overall prevalence of Anisakis larvae was 25% (95% confidence limits: 13
      41%), and the mean intensity was 19.1 (bootstrap 95% confidence limits: 15.3
      25.5). Recognized zoonotic A. simplex (s.s.) larvae found in imported Atlantic
      mackerel could represent a risk. Those who consume them could acquire parasitic
      allergies. The results will have an important impact on public health risk
      assessment in that they suggest reviewing critical control points at the Hazard
      Analysis Critical Control Point (HACCP) programmer to reduce the risk of anisakid
      induced allergies among consumers. Consequently, the present study provides the
      first data regarding the occurrence of A. simplex (s.s.) larvae in imported
      Atlantic mackerel in Turkish markets. 

PMID- 24935686
TI  - Alcohol at bedtime induces minor changes in sleep stages and blood gases in
      stable chronic obstructive pulmonary disease.
AB  - PURPOSE/BACKGROUND: The purpose of this study is to explore the effect of a
      moderate dose of alcohol on sleep architecture and respiration in chronic
      obstructive pulmonary disease (COPD). Alcohol depresses both hypercapnic and
      hypoxic ventilatory drives in awake, normal individuals and reduces the amount of
      rapid eye movement (REM) sleep and oxygen saturation (SpO2) in sleeping COPD
      subjects. METHODS: Prospectively designed, open-label interventional study in a
      pulmonary rehabilitation hospital. Twenty-six (nine males) stable inpatients,
      median forced expiratory volume first second (FEV1) 40.5 % of predicted, median
      age 65 years, investigated by polysomnography including transcutaneous
      measurement of carbon dioxide pressure increase (DeltaPtcCO2) in randomized order
      of either control sleep or intervention with 0.5 g of ethanol/kilogram
      bodyweight, taken orally immediately before lights off. RESULTS: Alcohol induced
      a mean increase (95 % confidence interval, [CI]) in the mean DeltaPtcCO2 of 0.10
      kPa (0.002-0.206, P = 0.047) and a mean decrease (CI) in the REM-sleep percentage
      of total sleep time (REM % of TST) of 3.1 % (0.2-6.0), (P = 0.020). Six subjects
      with apnea/hypopnea index (AHI) >=15 had fewer apneas/hypopneas during alcohol
      versus control sleep (mean reduction of AHI 11 (1-20), P = 0.046). Alcohol-sleep
      changes in SpO2, but not in DeltaPtcCO2, correlated with daytime arterial
      pressures of carbon dioxide (PaCO2) and oxygen (PaO2). CONCLUSION: Occasional use
      of a moderate, bedtime dose of alcohol has only minor respiratory depressant
      effects on the majority of COPD subjects, and in a minority even slightly
      improves respiration during sleep. However, caution is appropriate as this study
      is small and higher doses of alcohol may result in major respiratory depressive
      and additional negative health effects.

PMID- 24935688
TI  - Preventing adhesion of Escherichia coli O157:H7 and Salmonella Typhimurium LT2 on
      tomato surfaces via ultrathin polyethylene glycol film.
AB  - This work deals with adhesion of Escherichia coli O157:H7 and Salmonella enterica
      subsp. enterica serovar Typhimurium LT2 (S. Typhimurium LT2) on polyethylene
      glycol (PEG) coated tomato surfaces. PEG coating was characterized by water
      contact angle technique, scanning electron microscopy, and secondary ion mass
      spectrometry. It was shown that PEG films could physisorb on the tomato surfaces
      after the oxygen plasma treatment, which made some outermost layers of the
      surfaces hydrophilic. Bacterial adhesion on PEG coated tomato surface was studied
      by standard plate count, fluorescence microscopy, and scanning electron
      microscopy techniques. Fully covered PEG film reduced the bacterial attachment
      90% or more in comparison to the bare tomato surface. The degree of bacterial
      attachment decreased exponentially with increasing PEG coverage. When desired,
      PEG film could be removed by rinsing with water. Overall, this work demonstrates
      the proof-of-concept that an ultrathin film of polyethylene glycol may be used to
      effectively inhibit the attachment of pathogenic bacteria on tomato surfaces. 

PMID- 24935689
TI  - Toxin production and growth of pathogens subjected to temperature fluctuations
      simulating consumer handling of cold cuts.
AB  - It is crucial for the quality and safety of ready-to-eat (RTE) foods to maintain
      the cold chain from production to consumption. The effect of temperature abuse
      related to daily meals and elevated refrigerator temperatures on the growth and
      toxin production of Bacillus cereus, Bacillus weihenstephanensis and
      Staphylococcus aureus and the growth of Listeria monocytogenes and Yersinia
      enterocolitica was studied. A case study with temperature loggings in the
      domestic environment during Easter and Christmas holidays was performed to select
      relevant time and temperature courses. A model for bacterial surface growth on
      food using nutrient agar plates exposed to variations in temperatures was used to
      simulate food stored at different temperatures and exposed to room temperature
      for short periods of time. The results were compared with predicted growth using
      the modeling tool ComBase Predictor. The consumers exposed their cold cuts to
      room temperatures as high as 26.5 degrees C with an average duration of meals was
      47 min daily for breakfast/brunch during the vacations. Short (<= 2 h) daily
      intervals at 25 degrees C nearly halved the time the different pathogens needed
      to reach levels corresponding to the levels associated with human infection or
      intoxication, compared with the controls continuously stored at refrigerator
      temperature. Although the temperature fluctuations affected growth of both B.
      weihenstephanensis and S. aureus, toxin production was only detected at much
      higher cell concentrations than what has been associated with human
      intoxications. Therefore, growth of L. monocytogenes and Y. enterocolitica was
      found to be the limiting factor for safety. In combination with data on
      temperature abuse in the domestic environment, modeling programs such as ComBase
      Predictor can be efficient tools to predict growth of some pathogens but will not
      predict toxin production.

PMID- 24935690
TI  - The influence of serial repitching of Saccharomyces pastorianus on its karyotype
      and protein profile during the fermentation of gluten-free buckwheat and quinoa
      wort.
AB  - Gluten-free beer-like beverages from malted buckwheat and quinoa are somehow
      close to their commercial production, but rather high expenses are expected due
      to the relatively high price of grain, some technological adaptations of process
      and the need for external enzyme supplementation during mashing. One of the
      common and efficient cost reduction measures in the industrial scale is serial
      repitching of the yeast biomass, which has not been studied for the buckwheat and
      quinoa wort fermentation before. In that manner we have monitored possible
      changes in yeast's proteins and chromosomal DNA during eleven serial repitchings
      of the yeast Saccharomyces pastorianus strain TUM 34/70 for fermentation of the
      barley, buckwheat and quinoa wort. Karyotypes showed changes in regard to the raw
      materials used and many responsible candidate proteins are suggested which could
      cause these differences. Different relative expressions of some protein bands
      were also linked to the proteins involved in yeast stress response and proteins
      involved in fermentation performance. Results suggest that serial repitching of
      the strain TUM 34/70 seems suitable for the production of gluten-free beer-like
      beverages from buckwheat and quinoa. 

PMID- 24935691
TI  - Adverse Drug Reactions to Antiretroviral Therapy in HIV-Infected Patients at the
      Largest Public Hospital in Nicaragua.
AB  - OBJECTIVE: Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are an
      important cause of hospitalization, treatment discontinuation, and regimen
      changes in both developed and developing countries. This study is the first to
      examine and understand ADRs in HIV-infected patients in Nicaragua. METHODS: A
      retrospective descriptive study was conducted from May 2010 to March 2011, in a
      cohort of HIV-infected patients receiving ART at the largest public hospital in
      Managua, Nicaragua. Patients were identified based on ADRs reporting on a
      standardized antiretroviral pharmacotherapy form. Subsequently, chart reviews of
      these patients were performed in order to document the specific ADRs. RESULTS:
      Six hundred ninety-two patients on ART were included. The incidence of ADRs was
      6.4% (95% confidence interval [CI] 4.5-8.2). Females demonstrated a higher
      incidence, that is, 10.2% (95% CI 5.3-15.1, P = .020). Patients treated with
      combinations of zidovudine (ZDV)/lamivudine (3TC) and emtricitabine
      (FTC)/tenofovir (TDF) had fewer ADRs (P < .01) than those using other
      combinations. Five patients were hospitalized or had a prolonged hospitalization
      secondary to ADRs, with no mortality attributed to ADR. The most common
      manifestations of ADRs were central nervous system (20 of 44), gastrointestinal
      (12 of 44), and dermatologic (8 of 44) reactions. Adverse drug reactions were
      classified as "likely ADRs" (25 of 44) and "possible ADRs" (19 of 44). No ADRs
      were preventable. CONCLUSION: Adverse drug reactions most frequently affected the
      central nervous system. No ADR was life threatening. The frequency of ADRs in
      this Nicaraguan patient population was less than that reported from other studies
      in resource-limited settings.

PMID- 24935692
TI  - Elements of Condom-Use Decision Making among South African Men Who Have Sex with
      Men.
AB  - South African men who have sex with men (MSM) are at increased risk for HIV
      infection, and male condoms are fundamental to HIV prevention programs. We
      explored condom use experiences through in-depth interviews with 34 South African
      MSM from Cape Town and Port Elizabeth. For data analysis, we generated a codebook
      and used the constant comparison method. Condom use reinforcing elements included
      use of alternative sexual strategies, having a high level of self-worth that was
      linked to protective behaviors, and use of ready-made condom negotiation scripts.
      Elements inhibiting condom use included perceiving substantial declines in sexual
      pleasure/performance, experiences of condom failure (possibly related to
      petroleum-based lubricant), and being in trusted relationships. Our findings
      suggest nuanced HIV prevention approaches such as bolstering condom negotiation
      skills based on successful tactics already in use. Further research is needed to
      address how to mitigate perceptions and experiences that condoms negatively
      impact sexual pleasure and performance.

PMID- 24935693
TI  - Glioblastoma Multiforme in an HIV-Infected Patient: An Unexpected Diagnosis.
AB  - We reported a case of glioblastoma multiforme in a 42-year-old female patient
      with HIV infection, who had a rapid progression to AIDS. She was diagnosed with
      an intracerebral mass and treated as neurotoxoplasmosis with improvement in the
      first week of therapy. On the fourth week she had a clinical worsening evolving
      to death, receiving the diagnosis at necropsy.

PMID- 24935694
TI  - In-Country Migration and Risk Factors for HIV Acquisition among Pregnant Women in
      Tijuana, Mexico.
AB  - OBJECTIVE: To compare HIV prevalence and HIV acquisition risk behaviors between
      pregnant women residents and migrants. DESIGN: A cross-sectional study of
      pregnant women of unknown HIV status seeking care at Tijuana General Hospital,
      Mexico. METHODS: Pregnant women attending the labor and delivery unit or the
      prenatal clinic had a rapid HIV test drawn, with positive results confirmed by
      Western blot. Migrants were defined as women who had resided in Tijuana for less
      than 5 years. RESULTS: Between 2007 and 2008, a total of 3331 pregnant women
      consented to participate. The HIV seroprevalence did not differ between Tijuana
      residents (18 of 2502, 0.72%) and migrants (3 of 829, 0.36%, P = .32). In
      multivariate regression analyses, HIV acquisition risk behaviors included
      methamphetamine use (adjusted odds ratio [OR]: 6.03, 95% confidence interval
      [CI]: 2.3-15.8, P < .001) and first presentation at labor (adjusted OR: 5.0, 95%
      CI: 1.6-15.3, P = .005), adjusted for migrant status, age, and history of
      sexually transmitted infections. CONCLUSION: The overall HIV seroprevalence was
      0.63% and did not differ between Tijuana residents and migrants.

PMID- 24935696
TI  - A hidden cause of virilization in postmenopausal women.

PMID- 24935695
TI  - Pretransplant IgG reactivity to apoptotic cells correlates with late kidney
      allograft loss.
AB  - Preexisting serum antibodies have long been associated with graft loss in
      transplant recipients. While most studies have focused on HLA-specific
      antibodies, the contribution of non-HLA-reactive antibodies has been largely
      overlooked. We have recently characterized mAbs secreted by B cell clones derived
      from kidney allograft recipients with rejection that bind to apoptotic cells.
      Here, we assessed the presence of such antibodies in pretransplant serum from 300
      kidney transplant recipients and examined their contribution to the graft
      outcomes. Kaplan-Meier survival analysis revealed that patients with high
      pretransplant IgG reactivity to apoptotic cells had a significantly increased
      rate of late graft loss. The effect was only apparent after approximately 1 year
      posttransplant. Moreover, the association between pretransplant IgG reactivity to
      apoptotic cells and graft loss was still significant after excluding patients
      with high reactivity to HLA. This reactivity was almost exclusively mediated by
      IgG1 and IgG3 with complement fixing and activating properties. Overall, our
      findings support the view that IgG reactive to apoptotic cells contribute to
      presensitization. Taking these antibodies into consideration alongside anti-HLA
      antibodies during candidate evaluation would likely improve the transplant risk
      assessment. 

PMID- 24935697
TI  - Primary thyroid lymphoma.

PMID- 24935698
TI  - High diagnostic accuracy and reproducibility of fine-needle aspiration cytology
      for diagnosing salivary gland tumors: cytohistologic correlation in 182 cases.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy and
      reproducibility of the cytologic diagnosis of salivary gland tumors (SGTs) using
      fine-needle aspiration cytology (FNAC). The study aimed to determine diagnostic
      accuracy, sensitivity, and specificity and to evaluate the extent of
      interobserver agreement. STUDY DESIGN: We retrospectively evaluated SGTs from the
      files of the Division of Pathology at the Clinics Hospital of Sao Paulo and
      Piracicaba Dental School between 2000 and 2006. RESULTS: We performed
      cytohistologic correlation in 182 SGTs. The sensitivity, specificity, positive
      predictive value, negative predictive value, and diagnostic accuracy were 94%,
      100%, 100%, 100%, and 99%, respectively. The interobserver cytologic
      reproducibility showed significant statistical concordance (P < .0001).
      CONCLUSIONS: FNAC is an effective tool for performing a reliable preoperative
      diagnosis in SGTs and shows high diagnostic accuracy and consistent interobserver
      reproducibility. Further FNAC studies analyzing large samples of malignant SGTs
      and reactive salivary lesions are needed to confirm their accuracy.

PMID- 24935699
TI  - pDsRed-EGFPmtag-, an effective dual fluorescent reporter system for cell-based
      screens of premature termination codon.
AB  - A large number of inherited diseases are caused by premature termination codon
      (PTC) mutations that lead to the degradation of mRNA template. In this report, we
      developed a dual fluorescent reporter that relied the feature of fluorescent
      protein coding region to express a fusion protein from pDsRed-EGFPmtag-.
      Expression of the fusion protein from a single reporter provides a sensitive
      approach for high-throughput screening of cell-specific PTC events in mixed cell
      cultures. Results from the read-through analysis of COS7 cells carrying the
      nonsense mutation pDsRed-EGFPmtag-Y445X treated by PTC 124 showed EGFP transcript
      level was increased in the COS7 cells treated by PTC124 in a dose-dependent
      manner. This novel reporter system was applicable to the majority of different
      PTC patterns and could be used to quantify efficiency of read-through within a
      single cell or select cells carrying PTC. 

PMID- 24935700
TI  - Effective management of oral potentially malignant disorders/precancers - a cost
      effective strategy for oral cancer prevention in India.

PMID- 24935701
TI  - Charge states of ions, and mechanisms of charge ordering transitions.
AB  - To gain insight into the mechanism of charge ordering transitions, which
      conventionally are pictured as a disproportionation of an ion M as 2M(n+)
      >M((n+1)+) + M((n-1)+), we (1) review and reconsider the charge state (or
      oxidation number) picture itself, (2) introduce new results for the putative
      charge ordering compound AgNiO2 and the dual charge state insulator AgO, and (3)
      analyze the cationic occupations of the actual (not formal) charge, and work to
      reconcile the conundrums that arise. We establish that several of the clearest
      cases of charge ordering transitions involve no disproportion (no charge transfer
      between the cations, and hence no charge ordering), and that the experimental
      data used to support charge ordering can be accounted for within density
      functional-based calculations that contain no charge transfer between cations. We
      propose that the charge state picture retains meaning and importance, at least in
      many cases, if one focuses on Wannier functions rather than atomic orbitals. The
      challenge of modeling charge ordering transitions with model Hamiltonians
      isdiscussed. 

PMID- 24935702
TI  - In vitro effectiveness of antimicrobial photodynamic therapy (APDT) using a 660
      nm laser and malachite green dye in Staphylococcus aureus biofilms arranged on
      compact and cancellous bone specimens.
AB  - The aim of this study was to evaluate the in vitro effectiveness of antimicrobial
      photodynamic therapy (APDT) using a 660 nm visible laser combined with malachite
      green (MG) dye in the inactivation of Staphylococcus aureus (ATCC 25923) biofilms
      formed within compact and cancellous bone specimens. Specimens of 80 compact
      bones and 80 cancellous bones were contaminated with a standard suspension of S.
      aureus and incubated for 14 days at 37  degrees C to allow for the formation of
      biofilms. The specimens were divided into the following groups (n = 10) according
      to the treatment conditions: PS-L - (control - no treatment), PS+L - (only MG for
      5 min), PS-L + 90 (only laser irradiation for 90 s), PS-L + 180 (only laser
      irradiation for 180 s), PS-L + 300 (only laser irradiation for 300 s), APDT90
      (APDT for 90 s), APDT180 (APDT for 180 s), and APDT300 (APDT for 300 s). The
      findings were statistically analyzed using an ANOVA 5%. All of the experimental
      groups were significantly different from the control group for both the compact
      and cancellous bone specimens. The compact bone specimens that received APDT
      treatment (for either 90, 180, or 300 s) showed reductions in the log10 CFU/ml of
      S. aureus by a magnitude of 4 log10. Cancellous bone specimens treated with 300 s
      of APDT showed the highest efficacy, and these specimens had a reduction in S.
      aureus CFU/ml by a factor of 3 log10. APDT treatment using these proposed
      parameters in combination with MG was effective at inactivating S. aureus
      biofilms in compact and cancellous bone specimens.

PMID- 24935706
TI  - Chronic kidney disease: Prenatal risk factors for kidney and urinary tract
      anomalies.

PMID- 24935708
TI  - Transplantation: Molecular diagnosis of kidney transplant rejection.

PMID- 24935710
TI  - Clinical trials: Off-pump coronary artery bypass graft surgery reduces
      postoperative AKI risk.

PMID- 24935705
TI  - Renal transplantation in autosomal dominant polycystic kidney disease.
AB  - In patients with autosomal dominant polycystic kidney disease (ADPKD) evaluated
      for kidney transplantation, issues related to native nephrectomy, cystic liver
      involvement, screening for intracranial aneurysms and living-related kidney
      donation deserve special consideration. Prophylactic native nephrectomy is
      restricted to patients with a history of cyst infection or recurrent haemorrhage
      or to those in whom space must be made to implant the graft. Patients with liver
      involvement require pretransplant imaging. Selection of patients for
      pretransplant screening of intracranial aneurysms should follow the general
      recommendations for patients with ADPKD. In living related-donor candidates aged
      <30 years and at-risk of ADPKD, molecular genetic testing should be carried out
      when ultrasonography and MRI findings are normal or equivocal. After kidney
      transplantation, patient and graft survival rates are excellent and the volume of
      native kidneys decreases. However, liver cysts continue to grow and treatment
      with a somatostatin analogue should be considered in patients with massive cyst
      involvement. Cerebrovascular events have a marginal effect on post-transplant
      morbidity and mortality. An increased risk of new-onset diabetes mellitus and
      nonmelanoma skin cancers has been reported, but several studies have challenged
      these findings. Finally, no data currently support the preferential use of
      mammalian target of rapamycin inhibitors as immunosuppressive agents in
      transplant recipients with ADPKD. 

PMID- 24935711
TI  - Choosing wisely in anesthesiology: the gap between evidence and practice.
AB  - To develop a "top-five" list of unnecessary medical services in anesthesiology,
      we undertook a multistep survey of anesthesiologists, most of whom were in
      academic practice, and a consequent iterative process with the committees of the
      American Society of Anesthesiologists. We generated a list of 18 low-value
      perioperative activities from American Society of Anesthesiologists practice
      parameters and the literature. Starting with this list and proceeding with a 2
      step survey using a 5-point Likert scale questionnaire, we eventually identified
      5 common activities that are of low quality or benefit and high cost and have
      poor evidence supporting their use. The 2 preoperative practices in the top-five
      list addressed the avoidance of unindicated baseline laboratory studies or
      diagnostic cardiac stress testing. The 3 intraoperative practices involved the
      avoidance of the routine use of the pulmonary artery for cardiac surgery and the
      use of packed red blood cells or colloid when not indicated. 

PMID- 24935712
TI  - Evaluating latent class models with conditional dependence in record linkage.
AB  - Record linkage methods commonly use a traditional latent class model to classify
      record pairs from different sources as true matches or non-matches. This approach
      was first formally described by Fellegi and Sunter and assumes that the agreement
      in fields is independent conditional on the latent class. Consequences of
      violating the conditional independence assumption include bias in parameter
      estimates from the model. We sought to further characterize the impact of
      conditional dependence on the overall misclassification rate, sensitivity, and
      positive predictive value in the record linkage problem when the conditional
      independence assumption is violated. Additionally, we evaluate various methods to
      account for the conditional dependence. These methods include loglinear models
      with appropriate interaction terms identified through the correlation residual
      plot as well as Gaussian random effects models. The proposed models are used to
      link newborn screening data obtained from a health information exchange. On the
      basis of simulations, loglinear models with interaction terms demonstrated the
      best misclassification rate, although this type of model cannot accommodate other
      data features such as continuous measures for agreement. Results indicate that
      Gaussian random effects models, which can handle additional data features,
      perform better than assuming conditional independence and in some situations
      perform as well as the loglinear model with interaction terms.

PMID- 24935713
TI  - Concept analysis of nurses' happiness.
AB  - PURPOSE: The purpose of this analysis is to examine and clarify the concept of
      nurses' happiness (NH), understand the different uses of the concept, explore the
      conditions that foster it, and consider the consequences of NH, including the
      phenomena that emerge as a result of NH occurrence. ORGANIZING FRAMEWORK: The
      author utilizes Walker and Avant's eight-stage concept analysis. METHODS:
      Computer and manual searches were conducted of articles in the English language
      addressing NH from 1990 to present. EBSCO and PubMed are the electronic databases
      used to access literature for this paper. For both databases, the researcher has
      examined this new term by splitting the term nurses' happiness into its two root
      words, namely nurses and happiness. An inductive analysis of articles produced
      descriptive themes. RESULTS: Definitions of happiness and NH are analyzed.
      Antecedents, attributes, and consequences of NH are described. Model, borderline,
      contrary, and related cases for NH are also identified. CONCLUSIONS: This concept
      analysis helps in the understanding of the definition of NH, the attributes that
      contribute to the occurrence of NH in clinical practice, as well as the
      consequences of NH, and how it should be measured from a nursing perspective.
      Ozkara San.

PMID- 24935714
TI  - Specific capture and detection of Staphylococcus aureus with high-affinity
      modified aptamers to cell surface components.
AB  - Slow off-rate modified aptamer (SOMAmer) reagents were generated to several
      Staphylococcus aureus cell surface-associated proteins via SELEX with multiple
      modified DNA libraries using purified recombinant or native proteins. High
      affinity binding agents with sub-nanomolar Kd 's were obtained for staphylococcal
      protein A (SpA), clumping factors (ClfA, ClfB), fibronectin-binding proteins
      (FnbA, FnbB) and iron-regulated surface determinants (Isd). Further screening
      revealed several SOMAmers that specifically bound to Staph. aureus cells from all
      strains that were tested, but not to other staphylococci or other bacteria. SpA
      and ClfA SOMAmers proved useful for the selective capture and enrichment of
      Staph. aureus cells, as shown by culture and PCR, leading to improved limits of
      detection and efficient removal of PCR inhibitors. Detection of Staph. aureus
      cells was enhanced by several orders of magnitude when the bacterial cell surface
      was coated with SOMAmers followed by qPCR of the SOMAmers. Furthermore,
      fluorescence-labelled SpA SOMAmers demonstrated their utility as direct detection
      agents in flow cytometry. Significance and impact of the study: Monitoring for
      microbial contamination of food, water, nonsterile products or the environment is
      typically based on culture, PCR or antibodies. Aptamers that bind with high
      specificity and affinity to well-conserved cell surface epitopes represent a
      promising novel type of reagents to detect bacterial cells without the need for
      culture or cell lysis, including for the capture and enrichment of bacteria
      present at low cell densities and for the direct detection via qPCR or
      fluorescent staining.

PMID- 24935716
TI  - Blending conjugated polymers without phase separation for fluorescent colour
      tuning of polymeric materials through FRET.
AB  - The fluorescence properties of conjugated polymer blends were investigated using
      a combination of excitation energy donor and acceptor conjugated polymers
      encapsulated by identical cyclic sidechains. Wearing this 'uniform', the polymers
      did not phase-separate in the blends. As such, these polymers provide an
      effective ensemble for designing fluorescent polymeric materials. 

PMID- 24935715
TI  - Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes gammadelta T
      cell commitment by enhancing TCR signal strength.
AB  - Friend leukemia integration 1 (Fli-1) is a member of the Ets transcription factor
      family and is expressed during T-cell development; however, the role Fli-1 plays
      in early T-cell differentiation has not been elucidated. In this report, we
      demonstrate that in mouse, Fli-1 overexpression retards the CD4(-) CD8(-) double
      negative (DN) to CD4(+) CD8(+) double-positive (DP) transition by deregulating
      normal DN thymocyte development. Specifically, Fli-1 expression moderates the DN2
      and DN3 developmental transitions. We further show that Fli-1 overexpression
      partially mimics strong TCR signals in developing DN thymocytes and thereby
      enhances gammadelta T-cell development. Conversely, Fli-1 knockdown by small
      hairpin RNA reverses the lineage bias from gammadelta T cells and directs DN
      cells to the alphabeta lineage by attenuating TCR signaling. Therefore, Fli-1
      plays a critical role in both the DN2 to DN3 transition and alphabeta/gammadelta
      lineage commitment. 

PMID- 24935717
TI  - Revisiting NMR through-space J(FF) spin-spin coupling constants for getting
      insight into proximate F---F interactions.
AB  - At present times it is usual practice to mark biological compounds replacing an H
      for an F atom to study, by means of (19)F NMR spectroscopy, aspects such as
      binding sites and molecular folding features. This interesting methodology could
      nicely be improved if it is known how proximity interactions on the F atom affect
      its electronic structure as gauged through high-resolution (19)F NMR
      spectroscopy. This is the main aim of the present work and, to this end,
      differently substituted peri-difluoronaphthalenes are chosen as model systems. In
      such compounds are rationalized some interesting aspects of the diamagnetic and
      paramagnetic parts of the (19)F nuclear magnetic shielding tensor as well as the
      transmission mechanisms for the PSO and FC contributions to (4)JF1F8 indirect
      nuclear spin-spin coupling constants. 

PMID- 24935720
TI  - PLD3 in Alzheimer's disease.
AB  - Rare coding variants in the phospholipase D3 (PLD3) gene, also known as HU-K4,
      have recently been identified to increase the risk for late-onset Alzheimer's
      disease (LOAD) by the whole exome sequencing (WES) in 14 large LOAD families and
      follow-up analyses of the candidate variants in several large independent LOAD
      case-control data series. PLD3 is highly expressed in the brain, especially
      mainly in neurons, but at a lower level in almost all tissues. The level of PLD3
      was found to be downregulated in Alzheimer's disease (AD) brains, which was
      negatively correlated with amyloid precursor protein (APP) and amyloid-beta
      (Abeta) levels. These findings suggested that PLD3 might be involved in AD
      pathogenesis through APP processing. Here, we briefly summarize the biochemical
      properties of PLD3, review recent genetic and expression findings of PLD3 that
      related to AD, and also speculate on the possible roles of PLD3 in the
      progression of this disease. Based on the contributing effects of PLD3 in AD
      pathogenesis, targeting PLD3 may provide new opportunities for AD therapeutic
      strategies.

PMID- 24935718
TI  - The role of phosphoinositides in synapse function.
AB  - Since the discovery of phosphatidylinositol-3-kinase, scientific interest in the
      biological functions of phosphoinositides has greatly increased. Currently, seven
      phosphoinositides have been identified. These phosphoinositides are specifically
      localized to organelle membranes, their site of action. Phosphoinositides can
      regulate neuronal function by specifically recruiting downstream proteins that
      have phosphoinositide-binding domains. To date, it is well accepted that
      phosphoinositides play important roles in a broad spectrum of neuronal functions
      from regulating neural development to modulating synapse function. This review
      will provide an overview of the function and distribution of phosphoinositides at
      synapses. 

PMID- 24935719
TI  - The neuronal activity-driven transcriptome.
AB  - Activity-driven transcription is a key event associated with long-lasting forms
      of neuronal plasticity. Despite the efforts to investigate the regulatory
      mechanisms that control this complex process and the important advances in the
      knowledge of the function of many activity-induced genes in neurons, as well as
      the specific contribution of activity-regulated transcription factors, our
      understanding of how activity-driven transcription operates at the systems
      biology level is still very limited. This review focuses on the research of
      neuronal activity-driven transcription from an "omics" perspective. We will
      discuss the different high-throughput approaches undertaken to characterize the
      gene programs downstream of specific activity-regulated transcription factors,
      including CREB, SRF, MeCP2, Fos, Npas4, and others, and the interplay between
      epigenetic and transcriptional mechanisms underlying neuronal plasticity changes.
      Although basic questions remain unanswered and important challenges still lie
      ahead, the refinement of genome-wide techniques for investigating the neuronal
      transcriptome and epigenome promises great advances. 

PMID- 24935721
TI  - Upregulation of SET expression by BACE1 and its implications in Down syndrome.
AB  - Down syndrome (DS) is one of the most common genetic diseases. Patients with DS
      display growth delay and intellectual disabilities and develop Alzheimer's
      disease (AD) neuropathology after middle age, including neuritic plaques and
      neurofibrillary tangles. Beta-site amyloid beta precursor protein (APP) cleaving
      enzyme 1 (BACE1), essential for Abeta production and neuritic plaque formation,
      is elevated in DS patients. However, its homolog, beta-site APP cleaving enzyme 2
      (BACE2), functions as theta-secretase and plays a differential role in plaque
      formation. In this study, by using Two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (2D SDS-PAGE) and LC-MS/MS proteomic profiling
      analysis, we found that the SET oncogene protein (SET) expression was associated
      with BACE1 but not BACE2. SET protein was increased in BACE1 overexpressing cells
      and was markedly reduced in the BACE1 knockout mice. We found that the
      overexpression of BACE1 or SET significantly inhibited cell proliferation.
      Moreover, knockdown of SET in BACE1 overexpression cells significantly rescued
      BACE1-induced cell growth suppression. Furthermore, both BACE1 and SET protein
      levels were increased in Down syndrome patients. It suggests that BACE1
      overexpression-induced SET upregulation may contribute to growth delay and
      cognitive impairment in DS patients. Our work provides a new insight that BACE1
      overexpression not only promotes neuritic plaque formation but may also
      potentiate neurodegeneration mediated by SET elevation in Alzheimer-associated
      dementia in DS.

PMID- 24935722
TI  - A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic
      T lymphocytes in T cells of smoldering myeloma patients.
AB  - We evaluated a cocktail of HLA-A2-specific peptides including heteroclitic XBP1
      US184-192 (YISPWILAV), heteroclitic XBP1 SP367-375 (YLFPQLISV), native CD138260
      268 (GLVGLIFAV) and native CS1239-247 (SLFVLGLFL), for their ability to elicit
      multipeptide-specific cytotoxic T lymphocytes (MP-CTLs) using T cells from
      smoldering multiple myeloma (SMM) patients. Our results demonstrate that MP-CTLs
      generated from SMM patients' T cells show effective anti-MM responses including
      CD137 (4-1BB) upregulation, CTL proliferation, interferon-gamma production and
      degranulation (CD107a) in an HLA-A2-restricted and peptide-specific manner.
      Phenotypically, we observed increased total CD3(+)CD8(+) T cells (>80%) and
      cellular activation (CD69(+)) within the memory SMM MP-CTL
      (CD45RO(+)/CD3(+)CD8(+)) subset after repeated multipeptide stimulation.
      Importantly, SMM patients could be categorized into distinct groups by their
      level of MP-CTL expansion and antitumor activity. In high responders, the
      effector memory (CCR7(-)CD45RO(+)/CD3(+)CD8(+)) T-cell subset was enriched,
      whereas the remaining responders' CTL contained a higher frequency of the
      terminal effector (CCR7(-)CD45RO(-)/CD3(+)CD8(+)) subset. These results suggest
      that this multipeptide cocktail has the potential to induce effective and durable
      memory MP-CTL in SMM patients. Therefore, our findings provide the rationale for
      clinical evaluation of a therapeutic vaccine to prevent or delay progression of
      SMM to active disease. 

PMID- 24935724
TI  - Histomorphometry in antigen-induced arthritis of the rabbit temporomandibular
      joint.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) of the temporomandibular joint
      (TMJ) can cause severe growth disturbances of the craniomandibular system.
      Antigen-induced arthritis (AIA) of the rabbit TMJ is simulating the inflammatory
      process of the TMJ in JIA. The aim of this study was to investigate the effect of
      a systemic administration of the tumor necrosis factor-alpha (TNF-alpha)
      antagonist etanercept on AIA in rabbits by means of three different histological
      staining methods. METHODS: After sensitization, a bilateral arthritis of the TMJ
      was induced and maintained by repeated intra-articular administrations of
      ovalbumin in 12 New Zealand white rabbits aged 10 weeks. From the 13th week of
      age, 6 of the 12 rabbits received weekly subcutaneous injections of etanercept,
      and the other 6 animals remained without therapy. Another 6 animals served as
      controls, receiving no treatment or intra-articular injections at all. After
      euthanasia at the age of 22 weeks, all TMJs were retrieved en bloc. Sagittal
      sections were cut and stained with hematoxylin-eosin (H-E), Safranin-O for the
      evaluation of the Mankin score, and tartrate-resistant acid phosphatase (TRAP).
      RESULTS: In the arthritis group, a chronic inflammation with degeneration of the
      articular cartilage was visible. In the etanercept group, the signs of cartilage
      degeneration were significantly reduced but present. In contrast, the joints in
      the control group were inconspicuous. A strong correlation between the Mankin
      score and TRAP-positive cells could be found. CONCLUSIONS: Antigen-induced
      arthritis causes severe damage in the TMJ of young rabbits. An improvement seems
      to be achievable by a systemic administration of etanercept.

PMID- 24935725
TI  - Human intestinal microbial metabolism of naringin.
AB  - Naringin, a major flavonoid in citrus fruits, has been proved to be a promising
      antitussive candidate. It undertakes complicated metabolism. In this study, human
      intestinal microbial metabolism of naringin was studied in vitro. Six persons'
      fecal water, which have intestinal microbial enzyme, were used in the first
      experiment. Naringin was metabolized by fecal water into naringenin.
      Subsequently, 3-(4-hydroxyphenyl)propionic acid (4-HPPA) was produced with
      naringenin degradation by a person's fecal water. However, 4-HPPA was not
      detected after naringenin degradation by the other 5 subjects' fecal water and
      the reason might be that the degrading velocity of 4-HPPA exceeded the producing
      velocity. To confirm the difference in degrading 4-HPPA among human feces, 22
      healthy persons' feces were used for incubation. In this second experiment, 15
      persons' feces could degrade 4-HPPA, but the other 7 subjects' could not. Human
      feces showed different ability of degrading 4-HPPA, and there are no gender
      differences. These results may be helpful for explaining findings in
      pharmacological and toxicological studies and are groundwork for clinical
      studies. 

PMID- 24935726
TI  - The direct synthesis of N-alkylated amides via a tandem hydration/N-alkylation
      reaction from nitriles, aldoximes and alcohols.
AB  - A novel strategy for the direct synthesis of N-alkylated amides from nitriles,
      aldoximes and alcohols was proposed and accomplished in the presence of a Cp*Ir
      complex. 

PMID- 24935723
TI  - Minimal morphological criteria for defining bone marrow dysplasia: a basis for
      clinical implementation of WHO classification of myelodysplastic syndromes.
AB  - The World Health Organization classification of myelodysplastic syndromes (MDS)
      is based on morphological evaluation of marrow dysplasia. We performed a
      systematic review of cytological and histological data from 1150 patients with
      peripheral blood cytopenia. We analyzed the frequency and discriminant power of
      single morphological abnormalities. A score to define minimal morphological
      criteria associated to the presence of marrow dysplasia was developed. This score
      showed high sensitivity/specificity (>90%), acceptable reproducibility and was
      independently validated. The severity of granulocytic and megakaryocytic
      dysplasia significantly affected survival. A close association was found between
      ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia
      and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with
      fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and
      increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations
      were significantly associated with a myelodysplastic phenotype. In myeloid
      disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia,
      increased CD34+ progenitors and chromosomal abnormalities are consistent with a
      diagnosis of MDS. The proposed morphological score may be useful to evaluate the
      presence of dysplasia in cases without a clearly objective myelodysplastic
      phenotype. The integration of cytological and histological parameters improves
      the identification of MDS cases among myeloid disorders with fibrosis and
      hypocellularity. 

PMID- 24935727
TI  - Women's experiences of working as a Clinical Teaching Associate teaching
      sensitive examinations: a qualitative study.
AB  - BACKGROUND: Increasingly, professional patient programs are used for training
      medical students to perform pelvic examinations, yet we know little of the
      experiences of women who teach medical students these sensitive examination
      skills. AIM: To describe the experiences of women working as Clinical Teaching
      Associates (CTAs) teaching medical students the technical and communication
      skills required to perform pelvic examinations. METHODS: Twelve women employed as
      CTAs participated in semi-structured interviews. Individual interviews were used
      to identify major themes in women's experiences of teaching sensitive
      examinations to medical students. RESULTS: CTAs identified unique difficulties in
      their work including negative attitudes from others towards their role and the
      unpleasantness of the examination, although other challenges (such as teamwork
      issues or providing negative feedback to colleagues) were characteristic of many
      work situations. Effective communication was identified as central to the CTA
      role and the women described growth in their communication skills and
      assertiveness that they applied to other aspects of their work and personal
      lives. CTAs were motivated to join the program and remained in the program
      because of an interest in women's health and a desire for meaningful work, which
      they believed improved the examination and communication skills of future
      doctors. Positive interactions with work colleagues were a valued part of the
      role and a primary motivator to remain in the program. CONCLUSIONS: Highlighting
      the experiences of women working as CTAs validates the significant teaching role
      these women perform and, from a pragmatic perspective, may increase understanding
      of the best way to attract and retain women to these important teaching roles.

PMID- 24935728
TI  - Expectations from different perspectives on future work outcome of young adults
      with intellectual and developmental disabilities.
AB  - PURPOSE: Expectations strongly influence future employment outcomes and social
      networks seem to mediate employment success of young adults with intellectual and
      developmental disabilities. The aim of this study is to examine the expectations
      of young adults with intellectual and developmental disabilities from special
      needs education, their parents and their school teachers regarding future work
      and the extent to which these expectations predict work outcome. METHODS: Data on
      341 young adults with intellectual or developmental disabilities, coming from
      special needs education, aged 17-20 years, and with an ability to work according
      to the Social Security Institute were examined. RESULTS: The school teacher's
      expectation was the only perspective that significantly predicted entering
      competitive employment, with a complementary effect of the expectation of parents
      and a small additional effect of the expectation of the young adult. CONCLUSIONS:
      Expectations of school teachers and parents are valuable in predicting work
      outcome. Therefore, it is important for professionals working with the young
      adult in the transition from school to work to incorporate the knowledge of
      school teachers and parents regarding the abilities of the young adult to enter
      competitive employment as a valuable source of information.

PMID- 24935729
TI  - Application of monoclonal antibodies generated against Panton-Valentine
      Leukocidin (PVL-S) toxin for specific identification of community acquired
      methicillin resistance Staphylococcus aureus.
AB  - Panton-Valentine Leukocidin (PVL) produced by community acquired methicillin
      Staphylococcus aureus (CA-MRSA) involved in skin and soft-tissue infections and
      necrotizing pneumonia comprised of two fractions, namely PVL S and PVL F. In the
      present study, three monoclonal antibodies designated as MAb1, MAb9 and MAb10
      were generated against recombinant PVL-S (35kDa) protein of S. aureus. All the
      three MAbs specifically reacted to confirm PVL-S positive strains of S. aureus
      recovered from clinical samples in Western blot analysis. Similarly all the three
      MAbs did not show any binding to other tested 14 different pathogenic bacteria
      belonging to other genera and species in Western blot analysis. Furthermore, a
      simple dot-ELISA method was standardized for the identification of PVL-S toxin
      containing S. aureus strains. Initially in dot-ELISA, Protein A (Spa) of S.
      aureus posed background noise problems due to the non-specific binding of
      antibodies resulting in false positive reactions. With the addition of 10mM
      diethylpyrocarbonate (DEPC) along with 5% milk in PBS in the blocking step
      prevented this non-specific binding of Spa to mouse anti-PVL monoclonal
      antibodies in dot-ELISA. Once standardized, this simple dot-ELISA was evaluated
      with nine PVL positive strains recovered from food, environmental and clinical
      samples and the results were compared with PCR assay for the presence of PVL
      toxin genes and also with Western blot analysis. A 100% correlation was found
      between dot-ELISA, PCR assay and Western blot analysis. Collectively our results
      suggest the newly developed simple dot-ELISA system can be of immense help in
      providing, rapid detection of the PVL toxin containing S. aureus strains at a
      relatively low cost and will be a valuable tool for the reliable identification
      of CA-MRSA. 

PMID- 24935730
TI  - Biofunctionalized self-propelled micromotors as an alternative on-chip
      concentrating system.
AB  - Sample pre-concentration is crucial to achieve high sensitivity and low detection
      limits in lab-on-a-chip devices. Here, we present a system in which self
      propelled catalytic micromotors are biofunctionalized and trapped acting as an
      alternative concentrating mechanism. This system requires no external energy
      source, which facilitates integration and miniaturization. 

PMID- 24935731
TI  - Measurement of dipole potential in bilayer lipid membranes by dielectric
      spectroscopy.
AB  - Planar bilayer lipid membranes formed from egg phosphatidylcholine in aqueous
      media containing the lipophilic anion, dipicrylamine (DPA), were studied by
      dielectric spectroscopy over a frequency range of 10 Hz-10 MHz. The membranes
      showed dielectric relaxation due to the translocation of DPA between the membrane
      interfaces. Incorporating either cholesterol or 6-ketocholestanol into the
      membranes increased the characteristic frequency of the relaxation, which is
      proportional to the translocation rate constant of DPA. The results suggested
      that the sterol dipoles induced positive potential changes within the membrane
      interior. The changes of the dipole potential were 70 mV for cholesterol and 150
      mV for 6-ketocholestanol when the sterol mole fraction was 0.67. The opposite
      effect was caused by phloretin added to the aqueous media, and the maximum dipole
      potential change was -90 mV at 100 MUM.

PMID- 24935737
TI  - Topological self-organization and prediction learning support both action and
      lexical chains in the brain.
AB  - A growing body of evidence in cognitive psychology and neuroscience suggests a
      deep interconnection between sensory-motor and language systems in the brain.
      Based on recent neurophysiological findings on the anatomo-functional
      organization of the fronto-parietal network, we present a computational model
      showing that language processing may have reused or co-developed organizing
      principles, functionality, and learning mechanisms typical of premotor circuit.
      The proposed model combines principles of Hebbian topological self-organization
      and prediction learning. Trained on sequences of either motor or linguistic
      units, the network develops independent neuronal chains, formed by dedicated
      nodes encoding only context-specific stimuli. Moreover, neurons responding to the
      same stimulus or class of stimuli tend to cluster together to form topologically
      connected areas similar to those observed in the brain cortex. Simulations
      support a unitary explanatory framework reconciling neurophysiological motor data
      with established behavioral evidence on lexical acquisition, access, and recall. 

PMID- 24935732
TI  - The role of microRNA in castration-resistant prostate cancer.
AB  - INTRODUCTION: Castration-resistant prostate cancer (CRPC) has a historically low
      median survival rate, but recent advances and discoveries in microRNAs (miRNAs)
      have opened the potential for new prognostication modalities to enhance
      therapeutic success. As new chemotherapies and immunotherapies are developed,
      there is an increasing need for precision and stratification of CRPC to allow for
      optimization and personalization of therapy. METHODS: A systematic literature
      review was conducted via electronic database resulting in the selection of 42
      articles based on title, abstract, study format, and content by a consensus of
      all participating authors. Most selected articles were published between 2002 and
      2013. In this review, we discuss the robustness of miRNAs as a biomarker
      platform, miRNAs associated with prostate cancer, and recent discoveries of miRNA
      associations with CRPC. RESULTS: The associations discovered have been of
      interest owing to the ability to differentiate between CRPC and localized
      prostate cancer. With the evaluation of multiple miRNAs, it is possible to
      provide a profile regarding tumor characteristics. Furthermore, actions of miRNAs
      on CRPC tumor cells have the ability to suppress metastatic phenotypes.
      CONCLUSION: miRNAs may have a growing role in CRPC prognostication and may
      potentially transform into a therapeutic potential.

PMID- 24935738
TI  - Trocar-sharpened needles for image-guided prostate biopsy improve sample quality
      and performance: first clinical results.
AB  - OBJECTIVE: To show the benefit of trocar-sharpened needles for image-guided
      prostate biopsy compared with standard bevelled needles in patients. MATERIALS
      AND METHODS: Twenty-four men underwent magnetic resonance imaging-targeted fusion
      guided transperineal saturation prostate biopsy, each with half standard bevelled
      and half trocar-sharpened needles. All taken biopsies were scored (1=worse to
      5=best) by one urologist for the following criteria. (1) Accuracy of matching
      between planned and performed biopsy. (2) Histologic quality of the sample. (3)
      Elegance, which is the easiness to take the biopsy in proper time, planned
      position, and best histologic quality. Afterward, the histologic sample quality
      was evaluated by a blinded pathologist. To show a possible training effect,
      blinded untrained junior residents performed biopsies in four men (103 cores).
      RESULTS: Overall, 600 single biopsies were analyzed. The trocar-sharpened needles
      demonstrated a significantly (p<0.05) better scoring for accuracy and elegance
      rated by the urologist. The histologic quality scored by the pathologist was
      superior. Moreover, significantly lower target errors with trocar-sharpened
      needles were achieved by untrained residents, but not by the experienced user.
      CONCLUSION: Using trocar-sharpened needles helps urologists to perform targeted
      prostate biopsy more elegantly and accurately. In addition, the histopathologic
      sample quality was superior, which may directly improve diagnostic certainty.
      There is an undeniable training effect in image-guided biopsy and unexperienced
      users can significantly reduce target errors with trocar-sharpened needles.

PMID- 24935739
TI  - Knowledge and awareness of dental implants among elderly people in Croatia.
AB  - PURPOSE: The use of inserted dental implants is growing every day in order to
      improve retention and stability of complete removable dental prostheses (RDPs),
      especially in the mandible. Therefore, the aim of this study was to examine the
      knowledge and awareness of dental implants among elderly people wearing complete
      RDPs. MATERIALS AND METHODS: This study, based on answers from a questionnaire
      designed for the purpose of this study, included 301 participants wearing
      complete RDPs from elderly care homes with average age of 74 years. RESULTS: The
      awareness of dental implants was statistically significantly (p < 0.05) affected
      by the participants' age, residence size, and their level of education. Younger
      participants (x- = 70 years) had heard about dental implants (56.5%; p < 0.05)
      and believed in the possibility of retaining complete RPDs using dental implants
      (56.1%; p < 0.05). Among participants living in places with populations of 10,000
      or fewer residents, more had not heard about dental implants (59.4%; p < 0.05).
      Among participants who had completed college/university or high school, there
      were a higher number of participants who had heard about dental implants (82.4%;
      p < 0.05). CONCLUSION: Although more than half of the participants had heard of
      dental implants, this did not mean they were well informed about the implant
      insertion procedure and the costs for such a treatment. In conclusion, awareness
      of dental implants in studied participants was insufficient. The results
      reinforce the need for better education and the provision of proper information
      to elderly people about dental implants and implant treatment options.

PMID- 24935740
TI  - Friction through reversible jumps of surface atoms.
AB  - We propose a microscopic model that incorporates the effect of thermally
      activated motion of surface atoms on nanoscopic friction. Our calculations
      demonstrate that the stick-slip motion of the tip is governed by two competing
      processes: (i) jumps of the surface atoms to the tip which tend to inhibit
      sliding, and (ii) jumps back to the sample which give rise to sliding. The energy
      dissipated during the reversible jumps of the surface atoms between the sample
      and tip contributes significantly to the friction force, and leads to a
      nonmonotonic dependence of friction on temperature, which has been observed in
      recent friction force microscopy experiments for different material classes. The
      proposed model elucidates the physical origin of microscopic instabilities
      introduced in phenomenological models for the interpretation of the experimental
      results. 

PMID- 24935741
TI  - A study of interleukin 1beta levels in peri-miniscrew crevicular fluid (PMCF).
AB  - BACKGROUND: This study provides a vital insight in assessing the clinical and
      biochemical changes in interleukin (IL)-1beta levels in peri-miniscrew crevicular
      fluid (PMCF) during the course of orthodontic tooth movement. METHODS: The study
      comprised the analysis of IL-1beta in peri-miniscrew crevicular fluid obtained
      from crevices around the miniscrews inserted in 11 patients (eight females and
      three males, mean age 17.3 +/- 4.64 years) with all first premolar extraction and
      maximum anchorage requirement using miniscrew-supported anchorage. Miniscrews
      were loaded at 3 weeks after placement by 200-g nitinol closed coil springs of 9
      mm length for en masse retraction. Peri-miniscrew crevicular fluid was collected
      at miniscrew placement (T1), at 3 weeks (T2/baseline) and on loading at 0 (T3)
      and 1 day (T4), 21 (T5), 72 (T6), 120 (T7), 180 (T8) and 300 (T9) days. IL-1beta
      levels were estimated by enzyme-linked immunosorbent assay (ELISA). Peri
      miniscrew tissue was examined for signs of inflammation, and also, miniscrew
      mobility was assessed with Periotest and handles of two mouth mirrors. RESULTS:
      IL-1beta levels in all miniscrews were significantly higher at T1 and peaked
      again at T4 showing a bimodal peak. However, there was a gradual and
      statistically significant decrease in IL-1beta till T5, while further changes
      till the end of the study were statistically not significant. CONCLUSIONS: The
      changing levels of IL-1beta levels in PMCF over a duration of 300 days are
      suggestive of the underlying inflammatory process. IL-1beta levels in PMCF show a
      significant rise during miniscrew insertion and on immediate loading. The trend
      of gradually reducing IL-1beta levels around the miniscrew over the period after
      loading towards baseline is suggestive of adaptive bone response to stimulus.

PMID- 24935742
TI  - Modeling ion channels: past, present, and future.
AB  - Ion channels are membrane-bound enzymes whose catalytic sites are ion-conducting
      pores that open and close (gate) in response to specific environmental stimuli.
      Ion channels are important contributors to cell signaling and homeostasis. Our
      current understanding of gating is the product of 60 plus years of voltage-clamp
      recording augmented by intervention in the form of environmental, chemical, and
      mutational perturbations. The need for good phenomenological models of gating has
      evolved in parallel with the sophistication of experimental technique. The goal
      of modeling is to develop realistic schemes that not only describe data, but also
      accurately reflect mechanisms of action. This review covers three areas that have
      contributed to the understanding of ion channels: traditional Eyring kinetic
      theory, molecular dynamics analysis, and statistical thermodynamics. Although the
      primary emphasis is on voltage-dependent channels, the methods discussed here are
      easily generalized to other stimuli and could be applied to any ion channel and
      indeed any macromolecule. 

PMID- 24935745
TI  - Thermo-reversible gelation of rod-coil and coil-rod-coil molecules based on
      poly(dimethyl siloxane) and perylene imides and self-sorting of the homologous
      pair.
AB  - Organogels with perylene derivatives and phthalocyanines reported in the
      literature so far involve self-assembly promoted by hydrogen bonds, in addition
      to aromatic and van der Waals interactions. Although the self assembly of these
      types of molecules without a hydrogen bonding group in the structure occurs in
      solution or during crystallization, the gelation studies reported so far
      incorporated a hydrogen bonding pair of the type N-H...O=C in the structure of
      the molecule. We present a case of thermo-reversible gelation without a hydrogen
      bonding group in the structure of (1) a coil-rod-coil molecule based on
      perylenetetracarboxylic diimide (PTCDI) and poly(dimethyl siloxane) (PDMS) and
      (2) a rod-coil molecule with perylene dicarboxylic imide (PDI) and PDMS. However
      IR spectroscopy shows the presence of multiple types of hydrogen bonding between
      the solvents and the gelator molecules. In addition, publications so far on
      gelation of perylene diimide based molecules involve groups attached to both
      imide nitrogens and with or without substitution in the bay position. We discuss
      here the gelation with a Mono-substituted perylene imide. The PDMS segment was
      attached to one side of PDI (Mono-PDMS) or to both imide nitrogens of PTCDI (Di
      PDMS). The Mono-PDMS is an inverse macromolecular surfactant applicable to non
      aqueous systems, and the Di-PDMS is a Gemini surfactant. The PDMS segment that we
      attached to PTCDI here is longer than most substituents used by other authors.
      These molecules gel propylamine, as well as mixed solvents of hexane-water and
      diisopropylamine-water. Both hexane and diisopropylamine dissolve Mono-PDMS and
      Di-PDMS at room temperature and addition of water results in precipitation.
      However, heating the solution to about 70  degrees C, adding water (5-15 wt%) and
      slowly cooling the solution, lead to gelation. The Di-PDMS forms fibers which are
      not flat but curved as an eaves trough. The Mono-PDMS forms hollow spheres.
      Although the Mono-PDMS and Di-PDMS are a homologous pair, blends of these do not
      show molecular intercalation during gelation, but self-sort. The fibers of Di
      PDMS based gels encapsulate the spheres of the Mono-PDMS based gels.

PMID- 24935743
TI  - Imaging P2X4 receptor subcellular distribution, trafficking, and regulation using
      P2X4-pHluorin.
AB  - P2X4 receptors are adenosine triphosphate (ATP)-gated cation channels present on
      the plasma membrane (PM) and also within intracellular compartments such as
      vesicles, vacuoles, lamellar bodies (LBs), and lysosomes. P2X4 receptors in
      microglia are up-regulated in epilepsy and in neuropathic pain; that is to say,
      their total and/or PM expression levels increase. However, the mechanisms
      underlying up-regulation of microglial P2X4 receptors remain unclear, in part
      because it has not been possible to image P2X4 receptor distribution within, or
      trafficking between, cellular compartments. Here, we report the generation of pH
      sensitive fluorescently tagged P2X4 receptors that permit evaluations of cell
      surface and total receptor pools. Capitalizing on information gained from
      zebrafish P2X4.1 crystal structures, we designed a series of mouse P2X4
      constructs in which a pH-sensitive green fluorescent protein, superecliptic
      pHluorin (pHluorin), was inserted into nonconserved regions located within
      flexible loops of the P2X4 receptor extracellular domain. One of these
      constructs, in which pHluorin was inserted after lysine 122 (P2X4-pHluorin123),
      functioned like wild-type P2X4 in terms of its peak ATP-evoked responses,
      macroscopic kinetics, calcium flux, current-voltage relationship, and sensitivity
      to ATP. P2X4-pHluorin123 also showed pH-dependent fluorescence changes, and was
      robustly expressed on the membrane and within intracellular compartments. P2X4
      pHluorin123 identified cell surface and intracellular fractions of receptors in
      HEK-293 cells, hippocampal neurons, C8-B4 microglia, and alveolar type II (ATII)
      cells. Furthermore, it showed that the subcellular fractions of P2X4-pHluorin123
      receptors were cell and compartment specific, for example, being larger in
      hippocampal neuron somata than in C8-B4 cell somata, and larger in C8-B4
      microglial processes than in their somata. In ATII cells, P2X4-pHluorin123 showed
      that P2X4 receptors were secreted onto the PM when LBs undergo exocytosis.
      Finally, the use of P2X4-pHluorin123 showed that the modulator ivermectin did not
      increase the PM fraction of P2X4 receptors and acted allosterically to potentiate
      P2X4 receptor responses. Collectively, our data suggest that P2X4-pHluorin123
      represents a useful optical probe to quantitatively explore P2X4 receptor
      distribution, trafficking, and up-regulation. 

PMID- 24935744
TI  - Calmodulation meta-analysis: predicting calmodulin binding via canonical motif
      clustering.
AB  - The calcium-binding protein calmodulin (CaM) directly binds to membrane transport
      proteins to modulate their function in response to changes in intracellular
      calcium concentrations. Because CaM recognizes and binds to a wide variety of
      target sequences, identifying CaM-binding sites is difficult, requiring intensive
      sequence gazing and extensive biochemical analysis. Here, we describe a
      straightforward computational script that rapidly identifies canonical CaM
      binding motifs within an amino acid sequence. Analysis of the target sequences
      from high resolution CaM-peptide structures using this script revealed that CaM
      often binds to sequences that have multiple overlapping canonical CaM-binding
      motifs. The addition of a positive charge discriminator to this meta-analysis
      resulted in a tool that identifies potential CaM-binding domains within a given
      sequence. To allow users to search for CaM-binding motifs within a protein of
      interest, perform the meta-analysis, and then compare the results to target
      peptide-CaM structures deposited in the Protein Data Bank, we created a website
      and online database. The availability of these tools and analyses will facilitate
      the design of CaM-related studies of ion channels and membrane transport
      proteins. 

PMID- 24935746
TI  - Unexplained anaemia in the elderly is characterised by features of low grade
      inflammation.

PMID- 24935747
TI  - Flaw in a disposable carbon dioxide absorber system.

PMID- 24935748
TI  - Plasma ropivacaine concentration following ultrasound-guided subcostal
      transversus abdominis plane block in adults.
AB  - Ultrasound-guided subcostal transversus abdominis plane block (TAPB) is widely
      used for abdominal surgery; however, arterial plasma concentration of the
      anesthetic ropivacaine after the blockade is still unclear. We evaluated
      ropivacaine concentration after subcostal TAPB in adult patients undergoing upper
      abdominal surgery. Twelve patients with American Society of Anesthesiologists
      physical status 1-2 were enrolled. They received ultrasound-guided subcostal TAPB
      with 0.45 % ropivacaine at 3 mg/kg. Arterial plasma samples were collected at 15,
      30, 45, 60, 90, and 120 min after the blockade and analyzed for total ropivacaine
      concentration using liquid chromatography and mass spectrometry. At every time
      point, the maximum concentrations (C(max)), and time to the C max (T(max)) were
      recorded. The mean C(max) and T(max) were 1.87 (0.78) ug/ml and 31.3 (16.7) min,
      respectively. No adverse events or clinical symptoms indicating systemic toxicity
      were observed during this study. The study demonstrated that administration of
      ropivacaine at 3 mg/kg during subcostal TAPB led to rapid increases in plasma
      concentration of the anesthetic during the first 2 h after the blockade. C(max)
      nearly reached the threshold for systemic toxicity.

PMID- 24935749
TI  - Pilot implementation of allied health assistant roles within publicly funded
      health services in Queensland, Australia: results of a workplace audit.
AB  - BACKGROUND: Allied health assistants provide delegated support for physical
      therapists, occupational therapists and other allied health professionals.
      Unfortunately the role statements, scope of practice and career pathways of these
      assistant positions are often unclear. To inform the future development of the
      allied health assistant workforce, a state-wide pilot project was implemented and
      audited. METHODS: New allied health assistant positions were implemented in
      numerous settings at three levels (trainee level, full (standard) scope and
      advanced scope level). Six months after implementation, 41 positions were
      audited, using a detailed on-site audit process, conducted by multiple audit
      teams. RESULTS: Thematically analysed audit findings indicated that both the full
      (standard) scope and the advanced scope positions were warranted, however the
      skills of the allied health assistants were not optimally utilised. Contributing
      factors to this underutilization included the reluctance of professionals to
      delegate clinical tasks, inconsistencies in role descriptions, limitations in
      training, and the time frame taken to reach an effective skill level.
      CONCLUSIONS: Optimal utilisation of assistants is unlikely to occur while
      professionals withhold delegation of tasks related to direct patient care. Formal
      clinical supervision arrangements and training plans should be established in
      order to address the concerns of professionals and accelerate full utilisation of
      assistants. Further work is necessary to identify the key components and
      distinguish key features of an advanced allied health assistant role.

PMID- 24935751
TI  - Recycling of carbon dioxide to methanol and derived products - closing the loop.
AB  - Starting with coal, followed by petroleum oil and natural gas, the utilization of
      fossil fuels has allowed the fast and unprecedented development of human society.
      However, the burning of these resources in ever increasing pace is accompanied by
      large amounts of anthropogenic CO2 emissions, which are outpacing the natural
      carbon cycle, causing adverse global environmental changes, the full extent of
      which is still unclear. Even through fossil fuels are still abundant, they are
      nevertheless limited and will, in time, be depleted. Chemical recycling of CO2 to
      renewable fuels and materials, primarily methanol, offers a powerful alternative
      to tackle both issues, that is, global climate change and fossil fuel depletion.
      The energy needed for the reduction of CO2 can come from any renewable energy
      source such as solar and wind. Methanol, the simplest C1 liquid product that can
      be easily obtained from any carbon source, including biomass and CO2, has been
      proposed as a key component of such an anthropogenic carbon cycle in the
      framework of a "Methanol Economy". Methanol itself is an excellent fuel for
      internal combustion engines, fuel cells, stoves, etc. It's dehydration product,
      dimethyl ether, is a diesel fuel and liquefied petroleum gas (LPG) substitute.
      Furthermore, methanol can be transformed to ethylene, propylene and most of the
      petrochemical products currently obtained from fossil fuels. The conversion of
      CO2 to methanol is discussed in detail in this review. 

PMID- 24935750
TI  - Assistance of ethyl glucuronide and ethyl sulfate in the interpretation of
      postmortem ethanol findings.
AB  - Postmortem ethanol formation is a well-known problem in forensic toxicology. The
      aim of this study was to interpret findings of ethanol in blood, in a large
      collection of forensic autopsy cases, by use of the nonoxidative ethanol
      metabolites, ethyl glucuronide (EtG), and ethyl sulfate (EtS). In this study,
      according to previously published literature, antemortem ethanol ingestion was
      excluded in EtS-negative cases. Among 493 ethanol-positive forensic autopsy
      cases, collected during the study period, EtS was not detected in 60 (12 %) of
      the cases. Among cases with a blood alcohol concentration (BAC) of <= 0.54 g/kg,
      antemortem ethanol ingestion was excluded in 38 % of the cases, while among cases
      with a BAC of >= 0.55 g/kg, antemortem ethanol ingestion was excluded in 2.2 % of
      the cases. For all cases where ethanol was measured at a concentration >1.0 g/kg,
      EtS was detected. The highest blood ethanol concentration in which EtS was not
      detected was 1.0 g/kg. The median concentrations of EtG and EtS in blood were 9.5
      MUmol/L (range: not detected (n.d.) 618.1) and 9.2 MUmol/L (range: n.d. 182.5),
      respectively. There was a statistically significant positive correlation between
      concentration levels of ethanol and of EtG (Spearman's rho=0.671, p<0.001) and
      EtS (Spearman's rho=0.670, p<0.001), respectively. In conclusion, this study
      showed that in a large number of ethanol-positive forensic autopsy cases, ethanol
      was not ingested before the time of death, particularly among cases where ethanol
      was present in lower blood concentrations. Routine measurement of EtG and EtS
      should therefore be recommended, especially in cases with BAC below 1 g/kg.

PMID- 24935752
TI  - Impact of drinking water conditions and copper materials on downstream biofilm
      microbial communities and Legionella pneumophila colonization.
AB  - AIMS: This study examined the impact of pipe materials and introduced Legionella
      pneumophila on downstream Leg. pneumophila colonization and microbial community
      structures under conditions of low flow and low chlorine residual. METHODS AND
      RESULTS: CDC biofilm(TM) reactors containing either unplasticized
      polyvinylchloride (uPVC) or copper (Cu) coupons were used to develop mature
      biofilms on Norprene(TM) tubing effluent lines to simulate possible in-premise
      biofilm conditions. The microbial communities were characterized through 16S and
      18S rRNA gene clone libraries and Leg. pneumophila colonization was determined
      via specific qPCR assays. The Cu significantly decreased downstream microbial
      diversity, approximately halved bacterial and eukaryotic abundance, with some
      groups only detected in uPVC-reactor tubing biofilms. However, some probable
      amoeba-resisting bacteria (ARB) like Mycobacterium spp. and Rhodobacteraceae were
      significantly more abundant in the Cu than uPVC-reactor tubing biofilms. In
      particular, Leg. pneumophila only persisted (postinoculation) within the Cu
      reactor tubing biofilms, and the controlled low chlorine residue and water flow
      conditions led to a general high abundance of possible free-living protozoa in
      all tubing biofilms. The higher relative abundance of ARB-like sequences from Cu
      coupons vs uPVC may have been promoted by amoebal selection and subsequent ARB
      protection from Cu inhibitory effects. CONCLUSIONS: Copper pipe and low flow
      conditions had significant impact on downstream biofilm microbial structures (on
      plastic pipe) and the ability for Leg. pneumophila colonization post an
      introduction event. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      report that compares the effects of copper and uPVC materials on downstream
      biofilm communities grown on a third (Norprene(TM)) surface material. The
      downstream biofilms contained a high abundance of free-living amoebae and ARB,
      which may have been driven by a lack of residual disinfectant and periodic
      stagnant conditions. Given the prevalence of Cu-piping in buildings, there may be
      increased risk from drinking water exposures to ARB following growth on
      pipe/fixture biofilms within premise drinking water systems.

PMID- 24935753
TI  - Associations between maternal depressive symptoms and child feeding practices in
      a cross-sectional study of low-income mothers and their young children.
AB  - BACKGROUND: Maternal depression may influence feeding practices important in
      determining child eating behaviors and weight. However, the association between
      maternal depressive symptoms and feeding practices has been inconsistent, and
      most prior studies used self-report questionnaires alone to characterize feeding.
      The purpose of this study was to identify feeding practices associated with
      maternal depressive symptoms using multiple methodologies, and to test the
      hypothesis that maternal depressive symptoms are associated with less responsive
      feeding practices. METHODS: In this cross-sectional, observational study,
      participants (n = 295) included low-income mothers and their 4- to 8-year-old
      children. Maternal feeding practices were assessed via interviewer-administered
      questionnaires, semi-structured narrative interviews, and videotaped observations
      in home and laboratory settings. Maternal depressive symptoms were measured using
      the Center for Epidemiologic Studies-Depression scale (CES-D). Regression
      analyses examined associations between elevated depressive symptoms (CES-D score
      >=16) and measures of maternal feeding practices, adjusting for: child sex, food
      fussiness, number of older siblings; and maternal age, body mass index (BMI),
      education, race/ethnicity, single parent status, perceived child weight, and
      concern about child weight. RESULTS: Thirty-one percent of mothers reported
      depressive symptoms above the screening cutoff. Mothers with elevated depressive
      symptoms reported more pressuring of children to eat (beta = 0.29; 95% Confidence
      Interval (CI): 0.03, 0.54) and more overall demandingness (beta = 0.16; 95% CI:
      0.03, 0.29), and expressed lower authority in child feeding during semi
      structured narrative interview (Odds Ratio (OR) for low authority: 2.82; 95% CI:
      1.55, 5.12). In homes of mothers with elevated depressive symptoms, the
      television was more likely audible during meals (OR: 1.91; 95% CI: 1.05, 3.48)
      and mothers were less likely to eat with children (OR: 0.48; 95% CI: 0.27, 0.85).
      There were no associations between maternal depressive symptoms and encouragement
      or discouragement of food in laboratory eating interactions. CONCLUSIONS: Mothers
      with elevated depressive symptoms demonstrated less responsive feeding practices
      than mothers with lower levels of depressive symptoms. These results suggest that
      screening for maternal depressive symptoms may be useful when counseling on
      healthy child feeding practices. Given inconsistencies across methodologies,
      future research should include multiple methods of characterizing feeding
      practices and direct comparisons of different methodologies.

PMID- 24935754
TI  - Six-year single-center survey on AKI requiring renal replacement therapy:
      epidemiology and health care organization aspects.
AB  - Evidence regarding hospital-based acute kidney injury (AKI) reveals a continuous
      increase in incidence over the years, at least in intensive care units (ICU).
      Fewer reports are available for non critically-ill patients admitted to general
      or specialist wards other than ICU (non-ICU). The consequence of greater
      incidence is an increase in therapies such as dialysis; but how the health care
      organization deals with this problem is not clearly known. Here we quantified the
      incidence of dialysis-requiring AKI (AKI-D) among patients admitted to a
      University Hospital which serves a population of 354,000 inhabitants. Between
      2007 and 2012, the incidence of AKI-D increased from 209 to 410 per million
      population (pmp)/year; age of patients and cardiovascular comorbid pathologies
      also increased. AKI-D was more frequent in non-ICU and 32% of patients were
      admitted to ICU. Considering the site of treatment of non-ICU patients, in 2007
      the ratio of patients admitted to non-ICU wards apart from Nephrology to those
      admitted to Nephrology was 1:1, but in 2012 the ratio increased to 2.4:1 (p <
      0.05). The complexity of acute disease, measured with the New Simplified Acute
      Physiology Score (SAPS II), did not reveal differences over the years. The number
      of dialysis treatments/year increased by 82%, and the total hours/year increased
      by 86%. Low-efficiency daily dialysis was performed in 52.4% of patients admitted
      to ICU, but dialysis sessions longer than 8 h were performed in only 40% of
      cases. Overall, 6-year mortality was 48.8%, without significant differences over
      the years. Mortality in ICU was 65.6%, and in non-ICU 41.2% (p < 0.001). Dialysis
      treatments needed to be continued after hospital discharge in 21% of patients. We
      conclude that dialysis-requiring AKI is becoming more common, and that two-thirds
      of patients are admitted as non-ICU: in these patients, during the last year of
      the study, the treatment site was more frequently in non-ICUs other than
      Nephrology. Over the 6-year period, the local healthcare organization had to
      dispense 80% more dialysis treatments/year in terms of total number and hours of
      treatment. One-fifth of surviving patients needed to continue dialysis after
      hospital discharge. Our data highlight the public health importance of AKI and
      the need for adequate resources for Nephrology.

PMID- 24935756
TI  - Socioeconomic status and the reward value of smoking following tobacco
      abstinence: a laboratory study.
AB  - INTRODUCTION: Socioeconomic status (SES) indicators are robustly associated with
      smoking behaviors. Yet, the psychological mechanisms underlying relations are
      unclear. This study merged the socioecological construct of SES with laboratory
      psychological science to investigate how income, education, and employment status
      predicted the reward value of smoking following tobacco abstinence among a
      diverse sample of adult daily smokers. We hypothesized that participants with
      lower SES (i.e., less education, lower income, and unemployed) would experience
      greater abstinence-induced enhancement of the reward value of smoking. METHODS:
      Adult smokers (N = 240; 68.7% male; 51.7% Black, 33.8% White, 7.1% Latino, and
      7.5% other) attended 2 laboratory sessions (1 nonabstinent and 1 following 16-hr
      tobacco abstinence) involving behavioral assessment of (a) latency to smoking
      when delaying smoking was monetarily rewarded and (b) purchasing individual
      cigarettes. Generalized estimating equations were used to test the interaction
      between each SES variable (education, income, and employment) and abstinence
      state to illustrate whether participants with certain SES characteristics were
      more sensitive to the abstinence-induced enhancement of the relative reward value
      of smoking. RESULTS: Participants who never attended college (vs. college
      attendees) exhibited greater abstinence-induced enhancement of the reward value
      of smoking, which was indicated by reduced willingness to delay smoking for money
      (ps = .03). Income and employment status did not moderate abstinence effects.
      CONCLUSIONS: Less-educated smokers were particularly motivated to smoke during
      acute abstinence. Observed educational disparities in smoking behaviors and
      smoking cessation might reflect a biased valuation of immediate drug-related
      (over less immediate alternative) rewards. Future research should explore
      potential mediators of this association.

PMID- 24935755
TI  - Smoking reductions and increased self-efficacy in a randomized controlled trial
      of smoking abstinence-contingent incentives in residential substance abuse
      treatment patients.
AB  - INTRODUCTION: Individuals with substance use disorders (SUDs) experience
      increased smoking-related morbidity and mortality but severely compromised
      smoking treatment benefits. Residential SUD treatment settings may be
      particularly positioned to target smoking, with ever-increasing smoking bans and
      culture shifts, but most smokers continue smoking. This study examined the
      effects of contingency management (CM) for increasing smoking abstinence in
      residential patients. METHODS: Smokers interested in quitting were recruited from
      a residential SUD program for men and were randomized to frequent smoking
      monitoring with behavioral support (monitoring; n = 21) or that plus smoking
      abstinence-contingent (expired carbon monoxide [CO] <= 6 ppm; urinary cotinine <=
      30ng/ml) incentives (CM, n = 24) for 4 weeks. After setting a quit date,
      procedures included daily behavioral support and smoking self-reports, 2 CO
      samples (a.m./p.m.) Monday through Friday, and cotinine tests on Mondays. CM
      participants received escalating draws for prizes ($1, $20, and $100 values) for
      negative tests; positive and missed samples reset draws. Follow-ups involved
      samples, self-reported smoking, and self-efficacy (weeks 4, 8, 12, and 24).
      RESULTS: Percent days CO-negative was higher with CM (median [interquartile
      range] 51.7% [62.8%]) compared to monitoring (0% [32.1%]) (p = .002). Cigarettes
      per day declined and point-prevalence abstinence increased through follow-up (p <
      .01), without significant group by time effects (p > .05). Abstinence self
      efficacy increased overall during the intervention and more with CM compared to
      monitoring and was associated with abstinence across conditions through follow
      up. CONCLUSIONS: CM improved some measures of response to smoking treatment in
      residential SUD patients.

PMID- 24935757
TI  - Randomized trial of telephone-delivered acceptance and commitment therapy versus
      cognitive behavioral therapy for smoking cessation: a pilot study.
AB  - OBJECTIVE: We conducted a pilot randomized trial of telephone-delivered
      acceptance and commitment therapy (ACT) versus cognitive behavioral therapy (CBT)
      for smoking cessation. METHOD: Participants were 121 uninsured South Carolina
      State Quitline callers who were adult smokers (at least 10 cigarettes/day) and
      who wanted to quit within the next 30 days. Participants were randomized to 5
      sessions of either ACT or CBT telephone counseling and were offered 2 weeks of
      nicotine replacement therapy (NRT). RESULTS: ACT participants completed more
      calls than CBT participants (M = 3.25 in ACT vs. 2.23 in CBT; p = .001).
      Regarding satisfaction, 100% of ACT participants reported their treatment was
      useful for quitting smoking (vs. 87% for CBT; p = .03), and 97% of ACT
      participants would recommend their treatment to a friend (vs. 83% for CBT; p =
      .06). On the primary outcome of intent-to-treat 30-day point prevalence
      abstinence at 6 months postrandomization, the quit rates were 31% in ACT versus
      22% in CBT (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 0.7-3.4). Among
      participants depressed at baseline (n = 47), the quit rates were 33% in ACT
      versus 13% in CBT (OR = 1.2, 95% CI = 1.0-1.6). Consistent with ACT's theory,
      among participants scoring low on acceptance of cravings at baseline (n = 57),
      the quit rates were 37% in ACT versus 10% in CBT (OR = 5.3, 95% CI = 1.3-22.0).
      CONCLUSIONS: ACT is feasible to deliver by phone, is highly acceptable to
      quitline callers, and shows highly promising quit rates compared with standard
      CBT quitline counseling. As results were limited by the pilot design (e.g., small
      sample), a full-scale efficacy trial is now needed.

PMID- 24935759
TI  - Fibrotic airway stenosis following radiotherapy in patients with adenoid cystic
      carcinoma.
AB  - BACKGROUND AND OBJECTIVE: Radiotherapy is usually administered to the central
      airway in patients with unresectable adenoid cystic carcinoma (ACC). The purpose
      of this study was to describe the outcomes of endobronchial intervention in
      patients with airway stenosis following radiotherapy for ACC. Moreover, we
      investigated the incidence and contributing factors for airway stenosis following
      radiotherapy for ACC. METHODS: Forty-seven patients with ACC, who underwent
      radiotherapy of the tracheobronchial tree from January 1995 to December 2011,
      were reviewed retrospectively. Fibrotic airway stenoses were diagnosed using
      three-dimensional computed tomography, flexible bronchoscopy or both. RESULTS:
      Eleven (23%) of the 47 patients with ACC suffered fibrotic airway stenosis
      following radiotherapy and received bronchoscopic intervention. The median
      interval from radiotherapy to diagnosis of fibrotic airway stenosis was 7 months.
      Low forced expiratory volume in 1 s (FEV1), FEV1 /forced vital capacity and
      brachytherapy were verified as factors contributing to radiotherapy-induced
      airway stenosis. Bronchoscopic intervention provided both symptomatic relief and
      improvement of lung function, and no procedure-related death or major
      complication was observed. Insertion of a straight silicone stent was required in
      10 patients (91%), and 4 (36%) eventually received Y-shaped silicone stents. The
      stents, once implanted, could not be removed in any of the patients; stents were
      well-tolerated for a prolonged period in all patients. CONCLUSIONS: Fibrotic
      airway stenosis following radiotherapy in patients with ACC is often found.
      Bronchoscopic intervention, including silicone airway stenting, was a safe and
      useful method for treating radiotherapy-induced fibrotic airway stenosis in
      patients with ACC.

PMID- 24935758
TI  - Short-echo three-dimensional H-1 MR spectroscopic imaging of patients with glioma
      at 7 Tesla for characterization of differences in metabolite levels.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of using a
      short echo time, three-dimensional H-1 magnetic resonance spectroscopic imaging
      (MRSI) sequence at 7 Tesla (T) to assess the metabolic signature of lesions for
      patients with glioma. METHODS: Twenty-nine patients with glioma were studied.
      MRSI data were obtained using CHESS water suppression, spectrally selective
      adiabatic inversion-recovery pulses and automatically prescribed outer-volume
      suppression for lipid suppression, and spin echo slice selection (echo time = 30
      ms). An interleaved flyback echo-planar trajectory was applied to shorten the
      total acquisition time (~10 min). Relative metabolite ratios were estimated in
      tumor and in normal-appearing white and gray matter (NAWM, GM). RESULTS: Levels
      of glutamine, myo-inositol, glycine, and glutathione relative to total creatine
      (tCr) were significantly increased in the T2 lesions for all tumor grades
      compared with those in the NAWM (P < 0.05), while N-acetyl aspartate to tCr were
      significantly decreased (P < 0.05). In grade 2 gliomas, level of total choline
      containing-compounds to tCr was significantly increased (P = 0.0137), while
      glutamate to tCr was significantly reduced (P = 0.0012). CONCLUSION: The improved
      sensitivity of MRSI and the increased number of metabolites that can be evaluated
      using 7T MR scanners is of interest for evaluating patients with glioma. This
      study has successfully demonstrated the application of a short-echo spin-echo
      MRSI sequence to detect characteristic differences in regions of tumor versus
      normal appearing brain.

PMID- 24935760
TI  - Isolated shortness of breath in a woman with a history of Hodgkin lymphoma.
AB  - BACKGROUND: Isolated shortness of breath in the patient with a history of a
      malignancy creates a diagnostic challenge and serves as a source of anxiety.
      Although cancer recurrence is typically the first concern of the patient and the
      clinician, toxicities of anticancer therapies must also be considered. METHODS: A
      case of a 49-year-old woman with a distant history of Hodgkin lymphoma with 2
      months of progressive dyspnea is presented and discussed. RESULTS: Although the
      patient was found to have bilateral pleural and pericardial effusions that were
      concerning for a recurrence of malignancy, analysis and cytology of fluids were
      negative for cancer. Instead a diagnosis of effusive-constrictive pericarditis
      secondary to radiation therapy was made. CONCLUSION: When treating a patient with
      a history of malignancy who presents with dyspnea, it is important to consider
      the downstream effects related to cancer treatments, even decades later, to guide
      specific therapies and to assuage the patient's fears.

PMID- 24935761
TI  - High-mobility group box-1 in sterile inflammation.
AB  - High-mobility group box 1 (HMGB1) was originally defined as a ubiquitous nuclear
      protein, but it was later determined that the protein has different roles both
      inside and outside of cells. Nuclear HMGB1 regulates chromatin structure and gene
      transcription, whereas cytosolic HMGB1 is involved in inflammasome activation and
      autophagy. Extracellular HMGB1 has drawn attention because it can bind to related
      cell signalling transduction receptors, such as the receptor for advanced
      glycation end products, Toll-like receptor (TLR)2, TLR4 and TLR9. It also
      participates in the development and progression of a variety of diseases. HMGB1
      is actively secreted by stimulation of the innate immune system, and it is
      passively released by ischaemia or cell injury. This review focuses on the
      important role of HMGB1 in the pathogenesis of acute and chronic sterile
      inflammatory conditions. Strategies that target HMGB1 have been shown to
      significantly decrease inflammation in several disease models of sterile
      inflammation, and this may represent a promising clinical approach for treatment
      of certain conditions associated with sterile inflammation. 

PMID- 24935763
TI  - Simultaneous determination of major type B trichothecenes and deoxynivalenol-3
      glucoside in animal feed and raw materials using improved DSPE combined with LC
      MS/MS.
AB  - A simple and reliable method for simultaneous determination of deoxynivalenol-3
      glucoside and major type B trichothecenes (deoxynivalenol, nivalenol, fusarenon
      X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol and deepoxy-deoxynivalenol) in
      animal feed and raw materials has been developed and validated in this study. The
      method was based on an improved dispersive solid-phase extraction (DSPE) followed
      by analysis using high performance liquid chromatography coupled to tandem mass
      spectrometry (HPLC-MS/MS). Also, matrix-matched calibration curve (R(2)>0.99) was
      employed to minimize matrix effects and ensure accurate quantification. The
      recoveries during sample preparation process (including extraction and clean-up)
      ranged from 79.03% to 118.39%, with intra-day and inter-day relative standard
      deviation lower than 20% for all the analytes. The limit of quantification ranged
      from 5.0 MUg/kg for deoxynivalenol to 13.6 MUg/kg for fusarenon X. The validated
      method was successfully applied to the analysis of animal feed and corn. The
      pilot study showed that 37 out of 41 samples were contaminated with
      deoxynivalenol-3-glucoside at the levels of 6.0-121.0 MUg/kg. Most of the type B
      trichothecenes were also found with the exception of fusarenon X, at the
      contaminated levels of 10.0-1,382 MUg/kg. To the best of our knowledge, this was
      the first scientific report on the co-occurrence of masked deoxynivalenol and
      type B trichothecenes in animal feed and raw materials.

PMID- 24935764
TI  - In memory of Joan Cordoba.

PMID- 24935765
TI  - 'Hepatology' on the move.

PMID- 24935762
TI  - Comparative genomics of Riemerella anatipestifer reveals genetic diversity.
AB  - BACKGROUND: Riemerella anatipestifer is one of the most important pathogens of
      ducks. However, the molecular mechanisms of R. anatipestifer infection are poorly
      understood. In particular, the lack of genomic information from a variety of R.
      anatipestifer strains has proved severely limiting. RESULTS: In this study, we
      present the complete genomes of two R. anatipestifer strains, RA-CH-1 (2,309,519
      bp, Genbank accession CP003787) and RA-CH-2 (2,166,321 bp, Genbank accession
      CP004020). Both strains are from isolates taken from two different sick ducks in
      the SiChuang province of China. A comparative genomics approach was used to
      identify similarities and key differences between RA-CH-1 and RA-CH-2 and the
      previously sequenced strain RA-GD, a clinical isolate from GuangDong, China, and
      ATCC11845. CONCLUSION: The genomes of RA-CH-2 and RA-GD were extremely similar,
      while RA-CH-1 was significantly different than ATCC11845. RA-CH-1 is 140,000 bp
      larger than the three other strains and has 16 unique gene families. Evolutionary
      analysis shows that RA-CH-1 and RA-CH-2 are closed and in a branch with
      ATCC11845, while RA-GD is located in another branch. Additionally, the detection
      of several iron/heme-transport related proteins and motility mechanisms will be
      useful in elucidating factors important in pathogenicity. This information will
      allow a better understanding of the phenotype of different R. anatipestifer
      strains and molecular mechanisms of infection.

PMID- 24935766
TI  - Liver international - between tradition and innovation.

PMID- 24935767
TI  - Diabetes in athletes.
AB  - Diabetes is not necessarily as debilitating to a sportsperson's career as some
      people might think.With proper management, any sport is possible. Talha Khan
      Burki reports.

PMID- 24935768
TI  - Maternal morbidity of women receiving birth center care in New South Wales: a
      matched-pair analysis using linked health data.
AB  - BACKGROUND: Around 2 percent of women who give birth in Australia each year do so
      in a birth center. New South Wales, Australia's largest state, accounts for
      almost half of these births. Previous studies have highlighted the need for
      better quality data on maternal morbidity and mortality, to fully evaluate the
      safety of birth center care. AIMS: This study aimed to examine maternal morbidity
      related to birth center care for women in New South Wales. METHODS: A
      retrospective cohort study with matched-pairs was conducted using linked health
      data for New South Wales. Maternal outcomes were compared for women who intended
      to give birth in a birth center, matched with women who intended to give birth in
      the co-located hospital labor ward. RESULTS: Rates of maternal outcomes,
      including postpartum hemorrhage, retained placenta, and postpartum infection,
      were significantly lower in the birth center group, after controlling for
      demographic and institutional factors. Interventions such as cesarean section and
      episiotomy were also significantly lower in these women, and the rate of
      breastfeeding at discharge was higher. There existed no difference in length of
      stay, admission to ICU, or maternal mortality. CONCLUSIONS: Birth centers are a
      safe option for low-risk women; however, further research is required for some
      rare maternal outcomes.

PMID- 24935769
TI  - Tracheo-innominate artery fistula with severe motor and intellectual disability:
      incidence and therapeutic management.
AB  - OBJECTIVE: Tracheo-innominate artery fistula (TIF) is a rare but life-threatening
      complication following tracheostomy or tracheoesophageal diversion (TED).
      Although successful surgical intervention for TIF has been reported, few studies
      have been performed in patients with severe motor and intellectual disability
      (SMID). Therefore, we aimed to analyze TIF in patients with SMID to clarify the
      clinical variables predicting the occurrence and adequate management for
      lifesaving of TIF. METHODS: We retrospectively reviewed the records of patients
      with SMID undergoing surgical tracheostomy and TED between 2006 and 2012 and
      identified those with TIF. When TIF occurred, we obtained the clinical status and
      emergency management. RESULTS: Of 70 patients who underwent tracheostomy or TED
      during the study period, three patients had TIFs; in one case, TIF was avoided by
      ligation of the innominate artery before TED. The incidence of TIF in those
      undergoing tracheostomy and TED was 2.3% and 7.4%, respectively. The interval
      between tracheostomy and TIF was 14-50 months. CONCLUSIONS: Patients with SMID
      may have an increased risk of TIF. Prompt diagnosis and surgical intervention to
      control the bleeding is the only effective management at present.

PMID- 24935770
TI  - The PHLDB1 rs498872 (11q23.3) polymorphism and glioma risk: A meta-analysis.
AB  - The association between the rs498872 single nucleotide polymorphism (SNP) and
      glioma risk has been studied, but these studies have yielded conflicting results.
      In order to explore this association, we performed a meta-analysis. A
      comprehensive literature search was performed using PubMed and EMBASE database,
      with the last search up to August 23, 2013. Six articles including 10 case
      control studies in English with 18 002 controls and 8434 cases were eligible for
      the meta-analysis. Subgroup analyses were conducted by source of controls and
      ethnicity. The combined results showed that rs498872 polymorphism was
      significantly associated with glioma risks (TT vs CC: OR = 1.337, 95% CI = 1.222
      1.462; TC vs CC: OR = 1.173, 95% CI = 1.081-1.272; dominant model: OR = 1.199,
      95% CI = 1.101-1.306; recessive model: OR = 1.237, 95% CI = 1.135-1.347; additive
      model: OR = 1.156, 95% CI = 1.085-1.232). Moreover, there was increased cancer
      risk in all genetic models after stratification of the SNP data by the source of
      controls and ethnicity, and no evidence of publication bias was produced. Our
      meta-analysis suggested that rs498872 polymorphism was associated with increased
      risk of glioma. However, additional studies exploring the combined effects of
      rs498872 polymorphisms in Asian population should be investigated. 

PMID- 24935771
TI  - A multi-level analysis of the effects of age and gender stereotypes on trust in
      anthropomorphic technology by younger and older adults.
AB  - Previous research has shown that gender stereotypes, elicited by the appearance
      of the anthropomorphic technology, can alter perceptions of system reliability.
      The current study examined whether stereotypes about the perceived age and gender
      of anthropomorphic technology interacted with reliability to affect trust in such
      technology. Participants included a cross-section of younger and older adults.
      Through a factorial survey, participants responded to health-related vignettes
      containing anthropomorphic technology with a specific age, gender, and level of
      past reliability by rating their trust in the system. Trust in the technology was
      affected by the age and gender of the user as well as its appearance and
      reliability. Perceptions of anthropomorphic technology can be affected by pre
      existing stereotypes about the capability of a specific age or gender.
      PRACTITIONER SUMMARY: The perceived age and gender of automation can alter
      perceptions of the anthropomorphic technology such as trust. Thus, designers of
      automation should design anthropomorphic interfaces with an awareness that the
      perceived age and gender will interact with the user's age and gender

PMID- 24935772
TI  - Vomitting, pregnancy and gastric bypass: a bariatric emergency?

PMID- 24935773
TI  - ALS: Control ventilation, manage respiratory secretions and, when required,
      oversee the process of dying.

PMID- 24935774
TI  - Temperature and composition dependence of short-range order and entropy, and
      statistics of bond length: the semiconductor alloy (GaN)(1-x)(ZnO)(x).
AB  - We present total energy and force calculations for the (GaN)1-x(ZnO)x alloy. Site
      occupancy configurations are generated from Monte Carlo (MC) simulations, on the
      basis of a cluster expansion model proposed in a previous study. Local atomic
      coordinate relaxations of surprisingly large magnitude are found via density
      functional calculations using a 432-atom periodic supercell, for three
      representative configurations at x = 0.5. These are used to generate bond-length
      distributions. The configurationally averaged composition- and temperature
      dependent short-range order (SRO) parameters of the alloys are discussed. The
      entropy is approximated in terms of pair distribution statistics and thus related
      to SRO parameters. This approximate entropy is compared with accurate numerical
      values from MC simulations. An empirical model for the dependence of the bond
      length on the local chemical environments is proposed. 

PMID- 24935776
TI  - Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter
      Volume in the Ventral Brain of Preterm Born Adults.
AB  - Widespread brain changes are present in preterm born infants, adolescents, and
      even adults. While neurobiological models of prematurity facilitate powerful
      explanations for the adverse effects of preterm birth on the developing brain at
      microscale, convincing linking principles at large-scale level to explain the
      widespread nature of brain changes are still missing. We investigated effects of
      preterm birth on the brain's large-scale intrinsic networks and their relation to
      brain structure in preterm born adults. In 95 preterm and 83 full-term born
      adults, structural and functional magnetic resonance imaging at-rest was used to
      analyze both voxel-based morphometry and spatial patterns of functional
      connectivity in ongoing blood oxygenation level-dependent activity. Differences
      in intrinsic functional connectivity (iFC) were found in cortical and subcortical
      networks. Structural differences were located in subcortical, temporal, and
      cingulate areas. Critically, for preterm born adults, iFC-network differences
      were overlapping and correlating with aberrant regional gray-matter (GM) volume
      specifically in subcortical and temporal areas. Overlapping changes were
      predicted by prematurity and in particular by neonatal medical complications.
      These results provide evidence that preterm birth has long-lasting effects on
      functional connectivity of intrinsic networks, and these changes are specifically
      related to structural alterations in ventral brain GM. 

PMID- 24935775
TI  - Type 1 diabetes through the life span: a position statement of the American
      Diabetes Association.

PMID- 24935777
TI  - The Resting Brain of Alcoholics.
AB  - Chronic alcohol consumption affects multiple cognitive processes supported by far
      reaching cerebral networks. To identify neurofunctional mechanisms underlying
      selective deficits, 27 sober alcoholics and 26 age-matched controls underwent
      resting-state functional magnetic resonance imaging and neuropsychological
      testing. Functional connectivity analysis assessed the default mode network
      (DMN); integrative executive control (EC), salience (SA), and attention (AT)
      networks; primary somatosensory, auditory, and visual (VI) input networks; and
      subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive
      overlap of intrinsic connectivity in all brain networks examined, suggesting
      overall integrity of large-scale functional networks. Despite these similar
      patterns, connectivity analyses identified network-specific differences of weaker
      within-network connectivity and expanded connectivity to regions outside the main
      networks in alcoholics compared with controls. For AT and VI networks, better
      task performance was related to expanded connectivity in alcoholism, supporting
      the concept of network expansion as a neural mechanism for functional
      compensation. For default mode, SA, RW, and EC networks, both weaker within
      network and expanded outside-network connectivity correlated with poorer
      performance and mood. Current smoking contributed to some of these abnormalities
      in connectivity. The observed pattern of resting-state connectivity might reflect
      neural vulnerability of intrinsic networking in alcoholics and suggests a
      mechanism to explain signature impairments in EM, RW evaluation, and EC ability. 

PMID- 24935778
TI  - Neural Evidence for the Flexible Control of Mental Representations.
AB  - This study was designed to explore neural evidence for the simultaneous
      engagement of multiple mental codes while retaining a visual object in short-term
      memory (STM) and, if successful, to explore the neural bases of strategic
      prioritization among these codes. We used multivariate pattern analysis of fMRI
      data to track patterns of brain activity associated with three common mental
      codes: visual, verbal, and semantic. When participants did not know which
      dimension of a sample stimulus would be tested, patterns of brain activity during
      the memory delay indicated that a visual representation was quickly augmented
      with both verbal and semantic re-representations of the stimulus. The verbal code
      emerged as most highly activated, consistent with a canonical visual-to
      phonological recoding operation in STM. If participants knew which dimension of a
      sample stimulus would be tested, brain activity patterns were biased toward the
      probe-relevant stimulus dimension. Interestingly, probe-irrelevant neural states
      persisted at an intermediate level of activation when they were potentially
      relevant later in the trial, but dropped to baseline when cued to be irrelevant.
      These results reveal the neural dynamics underlying the creation and retention of
      mental codes, and they illustrate the flexible control that humans can exert over
      these representations. 

PMID- 24935780
TI  - Body size, nuptial pad size and hormone levels: potential non-destructive
      biomarkers of reproductive health in wild toads (Bufo bufo).
AB  - Amphibians are declining and fertility/fecundity are major drivers of population
      stability. The development of non-destructive methods to assess reproductive
      health are needed as destructive measures are fundamentally at odds with
      conservation goals for declining species. We investigated the utility of body
      size, nuptial pad size and forelimb width as non-destructive biomarkers of
      internal reproductive physiology, by analysing correlations with commonly used
      destructive methods in adult male toads (Bufo bufo) from a low human impact and a
      high human impact site. Principal component analyses revealed that size was the
      most important variable for explaining inter-individual differences in other
      measured endpoints, both non-destructive and destructive, except for hormone
      levels and nuptial pad, which were independent of size. Toads from the LI and the
      HI site differed in almost all of the measured endpoints; this was largely driven
      by the significantly smaller size of toads from the HI site. Correlational
      analyses within sites revealed that size was correlated with several reproductive
      endpoints in toads from the HI site but not the LI site, indicating a possible
      limiting effect of size on reproductive physiology. Intersex was observed in 33%
      of toads from the HI site and incidence was not related to any other measured
      endpoint. In conclusion, we provide evidence that size is associated with
      reproductive physiology and that nuptial pad/hormone levels have potential as
      additional markers due to their independence from size. We also show that human
      activities can have a negative effect on reproductive physiology of the common
      toad.

PMID- 24935779
TI  - Delayed remote ischemic postconditioning protects against transient cerebral
      ischemia/reperfusion as well as kainate-induced injury in rats.
AB  - To test the appropriateness of using delayed remote ischemic postconditioning
      against damage caused to the hippocampus by ischemia or apoptosis inducing
      intoxication, we chose 10-min normothermic ischemia induced by four-vessel
      occlusion or kainate injection (8 mg/kg i.p.) in rats. Ischemia alone caused the
      number of degenerated CA1 neurons after 7 days lasting reperfusion to be
      significantly (p<0.001) increased by 72.77%. Delayed remote ischemic
      postconditioning lasting 20 min was able to prevent massive increase in the
      neurodegeneration. The group with 10 min of ischemia and postconditioning after 2
      days of reperfusion had only 15.87% increase in the number of apoptotic neurons.
      Seven days after kainic acid injection the number of surviving neurons was 42.8%
      (p<0.001), but the portion of surviving pyramidal cells in the postconditioning
      group is more than 98%. Our data show that remote postconditioning, performed
      with 20 min of tourniquet ischemia applied to the hind limb, is a simple method
      able to effectively stop the onset of neurodegeneration and prevent occurrence of
      massive muscle cell necrosis, even when used 2 days after the end of the adverse
      event. Surviving neurons retained a substantial part of their learning and memory
      ability.

PMID- 24935783
TI  - Novel strategy for treating neural disease.

PMID- 24935781
TI  - The in vitro and in vivo anti-tumor effects of MTX-Fe3O 4-PLLA-PEG-PLLA
      microspheres prepared by suspension-enhanced dispersion by supercritical CO2.
AB  - The in vitro and in vivo anti-tumor efficacy of methotrexate-loaded Fe3O4-poly-L
      lactide-poly(ethylene glycol)-poly-L-lactide magnetic composite microspheres (MTX
      Fe3O4-PLLA-PEG-PLLA MCMs, MMCMs), which were produced by co-precipitation (C) and
      microencapsulation (M) in a supercritical process, was evaluated at various
      levels: cellular, molecular, and integrated. The results at the cellular level
      indicate that MMCMs (M) show a better anti-proliferation activity than raw MTX
      and could induce morphological changes of cells undergoing apoptosis. At the
      molecular level, MMCMs (M) lead to a significantly higher relative mRNA
      expression of bax/bcl-2 and caspase-3 than MMCMs (C) at 10 MUg mL(-1) (P<0.01);
      and the pro-caspase-3 protein expression measured by Western blot analysis also
      demonstrates that MMCMs (M) can effectively activate pro-caspase-3. At the
      integrated level, mice bearing a sarcoma-180 tumor are used; in vivo anti-tumor
      activity tests reveal that MMCMs (M) with magnetic induction display a much
      higher tumor suppression rate and lower toxicity than raw MTX. Pharmacokinetic
      studies show that MMCMs (M) with magnetic induction significantly increase the
      accumulation of MTX in the tumor tissue compared with the other treatments. These
      results suggest that the MMCMs (M) prepared by the SpEDS process have great
      potential to play a positive role in the magnetic targeted therapy field.

PMID- 24935782
TI  - A novel manganese complex LMnAc selectively kills cancer cells by induction of
      ROS-triggered and mitochondrial-mediated cell death.
AB  - We previously identified a novel synthesized metal compound, LMnAc
      ([L2Mn2(Ac)(H2O)2](Ac) (L=bis(2-pyridylmethyl) amino-2-propionic acid)). This
      compound exhibited significant inhibition on cancer cell proliferation and was
      more selective against cancer cells than was the popular chemotherapeutic reagent
      cisplatin. In this study, we further investigated the underlying molecular
      mechanisms of LMnAc-induced cancer cell death. We found that LMnAc achieved its
      selectivity against cancer cells through the transferrin-transferrin receptor
      system, which is highly expressed in tumor cells. LMnAc triggered cancer cells to
      commit autophagy and apoptosis, which was mediated by the mitochondrial pathway.
      Moreover, LMnAc disrupted mitochondrial function, resulting in mitochondrial
      membrane potential collapse and ATP reduction. In addition, LMnAc induced
      intracellular Ca(2+) overload and reactive oxygen species generation.
      Interestingly, its anticancer effect was significantly reduced following
      pretreatment with the antioxidant N-acetyl cysteine, indicating that reactive
      oxygen species triggered cell death. Altogether, our data suggest that LMnAc
      appears to be a selectively promising anticancer drug candidate.

PMID- 24935784
TI  - The estimation of calibration equations for variables with heteroscedastic
      measurement errors.
AB  - In clinical chemistry and medical research, there is often a need to calibrate
      the values obtained from an old or discontinued laboratory procedure to the
      values obtained from a new or currently used laboratory method. The objective of
      the calibration study is to identify a transformation that can be used to convert
      the test values of one laboratory measurement procedure into the values that
      would be obtained using another measurement procedure. However, in the presence
      of heteroscedastic measurement error, there is no good statistical method
      available for estimating the transformation. In this paper, we propose a set of
      statistical methods for a calibration study when the magnitude of the measurement
      error is proportional to the underlying true level. The corresponding sample size
      estimation method for conducting a calibration study is discussed as well. The
      proposed new method is theoretically justified and evaluated for its finite
      sample properties via an extensive numerical study. Two examples based on real
      data are used to illustrate the procedure.

PMID- 24935785
TI  - The two-year incidence of depression and anxiety disorders in spousal caregivers
      of persons with dementia: who is at the greatest risk?
AB  - OBJECTIVE: Caregivers of persons with dementia play an important and economically
      valuable role within society, but many may do so at a considerable cost to
      themselves. Knowing which caregivers have the highest risk of developing a mental
      disorder may contribute to better support of ultra-high-risk groups with
      preventive interventions. This study aims to describe the incidence of depression
      and anxiety disorders in caregivers and to identify its significant predictors.
      DESIGN: Prospective cohort study with a follow-up of 24 months. PARTICIPANTS: 181
      spousal caregivers of persons with dementia without a clinical depression or
      anxiety disorder at baseline. SETTING: Memory clinics, case management services,
      and primary care settings in the Netherlands. MEASUREMENTS: The onset of
      depression and anxiety was measured every 3 months with the MINI International
      Neuropsychiatric Interview, a structured diagnostic instrument for DSM-IV mental
      disorders. Potential predictors were assessed at baseline. RESULTS: 60% of the
      caregivers developed a depressive and/or anxiety disorder within 24 months: 37% a
      depression, 55% an anxiety disorder, and 32% both disorders. Sub-threshold
      depressive symptoms (Wald chi2=6.20, df=1, OR: 3.2, 95% CI: 1.28-8.03, p=0.013)
      and poor self-reported health of the caregiver (Wald chi2=5.56, df=1, OR: 1.17,
      95% CI: 1.03-1.34, p=0.018) at baseline were significant predictors of disorder
      onset. CONCLUSION: Spousal caregivers of persons with dementia have a high risk
      to develop a mental disorder. Indicators related to the caregiver's (mental)
      health rather than environmental stressors such as patient characteristics or
      interruption of caregivers' daily activities predict disorder onset and can be
      used to identify caregivers for whom supporting preventive interventions are
      indicated.

PMID- 24935786
TI  - Interdisciplinary chemical approaches for neuropathology.

PMID- 24935787
TI  - Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders.
AB  - Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter
      regulating a wide range of physiological and pathological functions via
      activation of heterogeneously expressed 5-HT receptors. Besides the important
      role of 5-HT receptors in the pathogenesis of depressive disorders and in their
      clinical medications, underlying mechanisms are far from being completely
      understood. This review focuses on possible cross talk between two serotonin
      receptors, 5-HT1A and the 5-HT7 . Although these receptors are highly co
      expressed in brain regions implicated in depression, and most agonists developed
      for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional
      interaction has not been yet established. It has been recently shown that 5-HT1A
      and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From
      the functional point of view, heterodimerization has been shown to play an
      important role in regulation of receptor-mediated signaling and internalization,
      suggesting the implication of heterodimerization in the development and
      maintenance of depression. Interaction between these receptors is also of
      clinical interest, because both receptors represent an important pharmacological
      target for the treatment of depression and anxiety.

PMID- 24935788
TI  - Disease-modifying anti-Alzheimer's drugs: inhibitors of human cholinesterases
      interfering with beta-amyloid aggregation.
AB  - AIMS: We recently described multifunctional tools (2a-c) as potent inhibitors of
      human Cholinesterases (ChEs) also able to modulate events correlated with Abeta
      aggregation. We herein propose a thorough biological and computational analysis
      aiming at understanding their mechanism of action at the molecular level.
      METHODS: We determined the inhibitory potency of 2a-c on Abeta1-42 self
      aggregation, the interference of 2a with the toxic Abeta oligomeric species and
      with the postaggregation states by capillary electrophoresis analysis and
      transmission electron microscopy. The modulation of Abeta toxicity was assessed
      for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with Abeta
      and with the Abeta-preformed fibrils were computationally analyzed. 2a-c toxicity
      profile was also assessed (human hepatocytes and mouse fibroblasts). RESULTS: Our
      prototypical pluripotent analogue 2a interferes with Abeta oligomerization
      process thus reducing Abeta oligomers-mediated toxicity in human neuroblastoma
      cells. 2a also disrupts preformed fibrils. Computational studies highlighted the
      bases governing the diversified activities of 2a. CONCLUSION: Converging
      analytical, biological, and in silico data explained the mechanism of action of
      2a on Abeta1-42 oligomers formation and against Abeta-preformed fibrils. This
      evidence, combined with toxicity data, will orient the future design of safer
      analogues.

PMID- 24935790
TI  - New kid on the pretransplant block: IgG recognizing apoptotic cells.

PMID- 24935789
TI  - Role(s) of the 5-HT2C receptor in the development of maximal dentate activation
      in the hippocampus of anesthetized rats.
AB  - AIMS: Substantial evidence indicates that 5-HT2C receptors are involved in the
      control of neuronal network excitability and in seizure pathophysiology. Here, we
      have addressed the relatively unexplored relationship between temporal lobe
      epilepsy (TLE), the most frequent type of intractable epilepsy, and 5-HT2CRs.
      METHODS: In this study, we investigated this issue using a model of partial
      complex (limbic) seizures in urethane-anesthetized rat, based on the phenomenon
      of maximal dentate activation (MDA) using 5-HT2C compounds, electrophysiology,
      immunohistochemistry, and western blotting techniques. RESULTS: The 5-HT2C
      agonists mCPP (1 mg/kg, i.p) and lorcaserin (3 mg/kg, i.p), but not RO60-0175 (1
      3 mg/kg i.p.), were antiepileptogenic reducing the MDA response duration. The
      selective 5-HT2C antagonist SB242084 (2 mg/kg, i.p) unveiled antiepileptogenic
      effects of RO60-0175 (3 mg/kg, i.p) but did not alter those induced by mCPP and
      lorcaserin. Compared with control rats, electrically stimulated rats showed an
      increase in glutamic acid decarboxylase levels and a heterogeneous decrease in 5
      HT2CR immunoreactivity in different hippocampal areas. CONCLUSIONS: In our animal
      model of TLE, mCPP and lorcaserin were anticonvulsant; likely acting on receptor
      subtypes other than 5-HT2C. Epileptogenesis induced early adaptive changes and
      reorganization in the 5-HT2CR and GABA systems.

PMID- 24935791
TI  - Development of a rapid cyprinid herpesvirus 2 detection method by loop-mediated
      isothermal amplification.
AB  - Cyprinid herpesvirus 2 (CyHV2) is a pathogen that causes severe disease and high
      mortality in goldfish and Prussian carp. We developed a six primer loop-mediated
      isothermal amplification (LAMP) assay targeting the intercapsomeric triplex
      protein gene. CyHV-2 DNA was 10-fold serially diluted (10(8)-10(0) copies MUl(
      1)) and was used as the template to determine primer sensitivity. LAMP assays
      were performed with DNA templates from other pathogens to determine specificity.
      The LAMP assay had an unequivocal detection limit of 10 copies MUl(-1), which was
      100 times lower than that of the polymerase chain reaction. Other pathogen
      strains were not amplified by the LAMP primers, indicating good specificity. SYBR
      Green I was added to visually detect the amplification products. Assay
      applicability was evaluated in 120 samples of Carassius auratus gibelio, and a
      positive rate of 92.5% was obtained. In conclusion, a conventional LAMP assay has
      high convenience, rapidity, sensitivity and specificity for detecting CyHV-2 in
      infected aquatic organisms. Significance and impact of the study: Herpesviral
      haematopoietic necrosis, caused by cyprinid herpesvirus 2 (CyHV-2), is a severe
      disease of goldfish and Prussian carp associated with high mortality. We
      developed a loop-mediated isothermal amplification (LAMP) assay to detect CyHV-2
      at relatively low plasmid DNA copy levels. The results show that the LAMP assay
      has a number of advantages (simple, sensitive, rapid and specific) over the
      conventional polymerase chain reaction and can be applied in the laboratory and
      field. Particularly, the method is highly applicable to facilitate surveillance
      and early diagnosis of CyHV-2.

PMID- 24935792
TI  - Implicit Learning of Written Regularities and Its Relation to Literacy
      Acquisition in a Shallow Orthography.
AB  - Some research on literacy acquisition suggests that implicit learning processes
      may be related to reading and writing proficiency in English, which is a deep
      orthography. However, little research has been done to determine if the same is
      true in shallow orthographies. Here, we investigated whether the implicit
      learning ability of third grade Spanish speaking children was related to their
      reading and writing abilities. Twenty eight children viewed pseudowords which all
      adhered to untaught graphotactic rules and were later assessed to determine their
      implicit learning of these rules. The children's reading and writing abilities
      were also assessed using standardized tests. No correlations were found between
      the participants' level of implicit learning and their performance on reading
      tasks or on a pseudoword writing task, suggesting that implicit learning is not
      strongly related to the acquisition of phonological regularities in a shallow
      orthography. A correlation was found between recognition of previously seen
      exemplars and the ability to spell inconsistent words which require word specific
      knowledge to resolve the spelling inconsistencies. This result suggests that
      implicit learning mechanisms may play a role in the acquisition of lexical
      knowledge and thus, in writing proficiency. 

PMID- 24935794
TI  - Experimental control: what does it mean for a participant to 'feel free'?

PMID- 24935793
TI  - Antibody-conjugated gold nanoparticle-based immunosensor for ultra-sensitive
      detection of troponin-T.
AB  - The technology presented in this study demonstrates the feasibility of
      integrating nanostructures onto the surface of an electrical platform to achieve
      enhanced detection of the cardiac biomarker, troponin-T. A polymer microcontact
      printing technique was modified using printed circuit boards as molds for the
      application of gold nanoparticles onto microelectrode-patterned glass substrates.
      The microelectrodes were designed to support electrical impedance spectroscopy
      measurements and fabricated using standard photolithography methods. Capture
      antibodies specific to troponin-T were functionalized onto the surface of gold
      nanoparticles by using a thiol-based cross-linking molecule. The antibody
      conjugated gold nanoparticles were stamped onto the electrodes using a matching
      pattern imprinted onto an elastomeric mold. As a control to validate the efficacy
      of the nanotextured surface on the glass substrate, an electroplated printed
      circuit board was also used. The incorporation of gold nanoparticles showed
      significant amplification of the electro-ionic signals generated through binding
      of the antigen to its capture antibody. Enhanced sensitivity was demonstrated
      through detection of the target biomarker in the femtogram per milliliter range
      in buffer solution and biological media. In the absence of gold nanoparticles,
      the sensor demonstrated detection of troponin-T at higher concentration points.
      This study illustrates a robust method for developing a more sensitive, label
      free biosensor. 

PMID- 24935795
TI  - How robust is the association between smoking and depression in adults? A meta
      analysis using linear mixed-effects models.
AB  - INTRODUCTION: Our objective was to use meta-analytic techniques to assess the
      strength of the overall relationship and role of potential moderators in the
      association between smoking and depression in adults. METHODS: Two popular health
      and social science databases (PubMed and PsycINFO) were systematically searched
      to identify studies which examined the association between adult smoking behavior
      and major depressive disorder (MDD) or depressive symptoms. A total of 85
      relevant studies were selected for inclusion. Studies were analyzed using a
      linear mixed effects modeling package ("lme4" for R) and the Comprehensive Meta
      Analysis program version 2. RESULTS: Multiple nested linear mixed-effects models
      were compared. The best fitting models were those that included only random study
      effects and smoking status. In cross-sectional studies, current smokers were more
      likely to be depressed than never smokers (OR=1.50, CI=1.39-1.60), and current
      smokers were more likely to be depressed than former smokers (OR=1.76, CI=1.48
      2.09). The few available prospective studies, that used the requisite statistical
      adjustments, also showed smokers at baseline had greater odds of incident
      depression at follow-up than never smokers (OR=1.62, CI=1.10-2.40). CONCLUSIONS:
      In cross-sectional studies, smoking was associated with a nearly two-fold
      increased risk of depression relative to both never smokers and former smokers.
      In the smaller set of prospective studies, the odds of subsequent depression were
      also higher for current than never smokers. Attesting to its robustness, the
      relationship between smoking and depression was exhibited across several
      moderators. Findings could help health care providers to more effectively
      anticipate co-occurring health issues of their patients. Several methodological
      recommendations for future research are offered.

PMID- 24935796
TI  - Emotion differentiation and alcohol-related problems: the mediating role of
      urgency.
AB  - Deficits in emotional and behavioral regulation figure prominently in etiological
      models of alcohol-related problems. This study tests a model linking poor
      differentiation of emotion to alcohol-related problems via urgency. The sample
      consisted of 102 undergraduates between the ages 18 and 24 who reported moderate
      to heavy alcohol consumption. As hypothesized, negative urgency mediated the
      relationship between negative emotion differentiation and alcohol-related
      problems. However, contrary to hypothesis, positive urgency was not associated
      with either positive emotion differentiation or alcohol-related problems and the
      indirect effect of positive emotion differentiation via positive urgency was not
      significant. Instead, positive emotion differentiation exhibited a significant
      direct effect on alcohol-related problems. This study provides an initial
      examination of connections between specificity in labeling emotions, behavioral
      disinhibition, and problematic alcohol use. These findings suggest that poor
      differentiation of negative emotion may foster impulsive behavior when negatively
      aroused. Whereas, impulsive behavior when positively aroused may reflect
      heightened sensitivity to positive reinforcement, which may not be related to
      reflective processes underlying emotion differentiation. 

PMID- 24935798
TI  - The mediating role of depressive symptoms in the relationship between adverse
      childhood experiences and smoking.
AB  - PURPOSE OF THE STUDY: Adverse childhood experiences (ACEs), including various
      types of abuse and other forms of household dysfunction (i.e. witnessing domestic
      violence, parental substance abuse, etc.), have been consistently linked to
      increased rates of health risk behaviors and negative health outcomes in
      adulthood. Using data from the 2010 Centers for Disease Control and Prevention's
      (CDC) annual, nationwide Behavioral Risk Factor Surveillance System (BRFSS)
      telephone survey, this study tested whether self-reported symptoms of depression
      mediate the significant relationship between the number of ACEs an individual
      reports (expressed as an "ACE score") and whether they are a current or past
      smoker. METHODS: A path model was produced using multiple regression, and
      indirect effects were tested using bootstrapping of 2000 samples. RESULTS:
      Results of analyses indicated that, among White, Asian, and Hispanic
      participants, self-reported depressive symptoms are indeed a significant, but
      only partial, mediator between participants' ACE score and their smoking status.
      CONCLUSIONS: These results suggest that for smokers of White, Hispanic, and Asian
      ethnicity, screening for a history of ACEs and treatment for depressive symptoms
      may be indicated. However, while depressive symptoms may explain some of the
      associations between ACEs and smoking, these results suggest that other,
      unexamined factors also contribute to this pathway.

PMID- 24935797
TI  - Marijuana use and intoxication among daily users: an intensive longitudinal
      study.
AB  - BACKGROUND: Most of the harm from marijuana use is experienced by daily users.
      Despite this, there has not been a detailed prospective description of daily
      marijuana use. METHODS: We recruited daily marijuana users (n=142) by internet
      ads, Craigslist, flyers, etc. Participants were mostly women (58%) with a mean
      age of 33 and 47% were minorities. Participants called an Interactive Voice
      Response phone system to report marijuana and other drug use daily for 3months.
      RESULTS: Participants averaged using marijuana 3.2 times per day. Almost all
      participants used multiple modes of delivery during the study.
      Bongs/vaporizers/pipes were the most common mode of use (45% of uses). Day-to-day
      variability in amount of use was relatively small. The median rating of
      intoxication was 3.8 on a 0-6 scale with no intoxication reported on 1% of days
      and severe intoxication on 24% of days. The large majority binge drank (71%) or
      used tobacco (73%). Fifteen during-study variables were associated with the
      frequency of marijuana use; running out of marijuana and social setting were the
      strongest correlates. Retrospective reports of "usual" use at study entry were
      often significantly different than daily reports of use during the study.
      CONCLUSIONS: This is the first detailed prospective description of daily
      marijuana use. Most users used multiple times/day, used multiple modes to
      administer marijuana, were often intoxicated, and under-reported high rates of
      using alcohol and tobacco. The frequency of marijuana use was especially
      influenced by social factors. These results will help future studies better
      describe daily marijuana use.

PMID- 24935799
TI  - The effect of dietary omega-3 polyunsaturated fatty acids on plasma lipids and
      lipoproteins of C57BL/6 mice is age and sex specific.
AB  - There is clear evidence of the effects of sex and age on the prevalence of
      cardiovascular disease. We investigated the interactions of dietary omega (n)-3
      polyunsaturated fatty acids (PUFA), sex, and age on plasma lipids and
      lipoproteins in the offspring of C57BL/6 mice exposed to high, medium, or low n-3
      PUFA at weaning and 16 weeks postweaning. There was an increase in plasma
      triglycerides from weaning to 16 weeks in male and female offspring; however, the
      high n-3 PUFA group showed a reduction in triglycerides in both sexes at 16
      weeks. High n-3 PUFA caused an increase in plasma LDL-cholesterol from weaning to
      16 weeks in male offspring; however, the LDL particle size was significantly
      larger in the high n-3 PUFA group. Plasma from male mice showed higher
      cholesterol efflux compared to females; high n-3 PUFA increased cholesterol
      efflux. Thus the effects of n-3 PUFA are age and sex dependent. 

PMID- 24935801
TI  - A cutaneous lymphoma mimicking superficial skin abscess in a child.

PMID- 24935800
TI  - Omega-3 fatty acids in cardiovascular disease--an uphill battle.
AB  - In cardiology, results of recent large intervention trials with eicosapentaenoic
      acid (EPA) plus docosahexaenoic acid (DHA) supplements were neutral. In contrast,
      in epidemiologic studies, an inverse relation between clinical events and intake
      of EPA+DHA was found which was steeper for higher levels of EPA+DHA. A
      standardized way of determining levels is the Omega-3 Index, which is the
      percentage of EPA+DHA of a total of 26 fatty acids measured in erythrocytes.
      According to current criteria, a low Omega-3 Index is a cardiovascular risk
      factor. What can explain this contradiction? Trial participants were recruited
      irrespective of their baseline status in EPA+DHA - an important predictor of
      events. Levels of EPA+DHA have a statistically normal distribution; together with
      the large inter-individual variability of levels' responding to increased intake,
      this created a large overlap of EPA+DHA levels between intervention and control
      groups. Moreover, trial participants were advised to take EPA+DHA supplements
      with breakfast, frequently a low fat meal, resulting in poor bioavailability. As
      a result, there is an urgent need for new intervention trials in cardiology, for
      which participants with a low baseline omega-3 index are recruited, and then
      treated with individually tailored doses of EPA+DHA to a prespecified target
      range. 

PMID- 24935802
TI  - An independent elderly woman with rapid onset of coma.
AB  - A 75-year-old woman was transferred from a local hospital because of rapid
      progression to coma preceded by lower back pain and recurrent falls.
      Cerebrospinal fluid analysis at the local hospital revealed increased protein
      with a slightly elevated white blood cell count. Our imaging studies revealed
      multiple punctate foci with nodular enhancement in the brain and multifocal
      cystic lesions on the chest and abdomen. The patient was empirically treated with
      antibiotics and corticosteroids without improvement. She died 3 days after
      transfer, and autopsy was performed. The differential diagnosis, pathologic
      findings, and final diagnosis are discussed. 

PMID- 24935803
TI  - Staff nurse clinical leadership: a concept analysis.
AB  - PURPOSE: The purpose of this article is to provide a concept analysis of staff
      nurse clinical leadership (SNCL). A clear delineation of SNCL will promote
      understanding and encourage communication of the phenomenon. Clarification of the
      concept will establish a common understanding of the concept, and advance the
      practice, education, and research of this phenomenon. METHODS: A review of the
      literature was conducted using several databases. The databases were searched
      using the following keywords: clinical leadership, nursing, bedside, staff nurse,
      front-line, front line, and leadership. The search yielded several sources;
      however, only those that focused on clinical leadership demonstrated by staff
      nurses in acute care hospital settings were selected for review. FINDINGS: SNCL
      is defined as staff nurses who exert significant influence over other individuals
      in the healthcare team, and although no formal authority has been vested in them
      facilitates individual and collective efforts to accomplish shared clinical
      objectives. CONCLUSION: The theoretical definition for SNCL within the team
      context will provide a common understanding of this concept and differentiate it
      from other types of leadership in the nursing profession. This clarification and
      conceptualization of the concept will assist further research of the concept and
      advance its practical application in acute care hospital settings.

PMID- 24935804
TI  - Fractionation of pitch intervals: an axiomatic study testing monotonicity,
      commutativity, and multiplicativity in musicians and non-musicians.
AB  - Direct ratio scaling (e.g., magnitude estimation; Stevens, 1956, American Journal
      of Psychology) is a widely used approach in psychophysics resting on the
      assumption that participants are able to refer to sensations with numbers that
      are valid on a ratio scale. Only recently, the necessary conditions of
      commutativity and multiplicativity have been formulated (Narens, 1996, Journal of
      Mathematical Psychology) and tested empirically, e.g., for the sensation of
      loudness. The present investigation evaluated these properties for the ratio
      production of pitch intervals. Musically trained (n = 10) and untrained (n = 11)
      participants adjusted intervals defined by two ascending pure-tone frequencies to
      given fractions (1/3, 1/2, 2/3), starting either from a 12 or 17-semitone
      standard pitch interval. The results show that the axioms of commutativity and
      multiplicativity held for most of the participants, irrespective of musical
      training. Furthermore, all participants produced larger frequency intervals in
      response to larger ratio numbers used in the instructions (monotonicity), but
      only musically trained participants were sensitive to the size of the standard
      interval (thus producing strictly increasing magnitudes). Overall, the results
      indicate that pitch intervals are ratio-scalable. However, restrictions must be
      made, especially for non-musical listeners, and when an octave is exceeded.

PMID- 24935805
TI  - Haptic guidance of overt visual attention.
AB  - Research has shown that information accessed from one sensory modality can
      influence perceptual and attentional processes in another modality. Here, we
      demonstrated a novel crossmodal influence of haptic-shape information on visual
      attention. Participants visually searched for a target object (e.g., an orange)
      presented among distractor objects, fixating the target as quickly as possible.
      While searching for the target, participants held (never viewed and out of sight)
      an item of a specific shape in their hands. In two experiments, we demonstrated
      that the time for the eyes to reach a target-a measure of overt visual attention
      was reduced when the shape of the held item (e.g., a sphere) was consistent with
      the shape of the visual target (e.g., an orange), relative to when the held shape
      was unrelated to the target (e.g., a hockey puck) or when no shape was held. This
      haptic-to-visual facilitation occurred despite the fact that the held shapes were
      not predictive of the visual targets' shapes, suggesting that the crossmodal
      influence occurred automatically, reflecting shape-specific haptic guidance of
      overt visual attention. 

PMID- 24935806
TI  - Visual statistical learning can drive object-based attentional selection.
AB  - Recent work on statistical learning has demonstrated that environmental
      regularities can influence aspects of perception, such as familiarity judgments.
      Here, we ask if statistical co-occurrences accumulated from visual statistical
      learning could form objects that serve as the units of attention (i.e., object
      based attention). Experiment 1 demonstrated that, after observers first viewed
      pairs of shapes that co-occurred in particular spatial relationships, they were
      able to recognize the co-occurring pairs, and were faster to discriminate two
      targets when they appeared within a learned pair ("object") than when the targets
      appeared between learned pairs, demonstrating an equivalent of an object-based
      attention effect. Experiment 2 replicated the results of Experiment 1 using a
      different set of shape pairs, and revealed a negative association between the
      attention effect and familiarity judgments of the co-occurred pairs. Experiment 3
      reports three control experiments that validated the task procedure and ruled out
      alternative accounts. 

PMID- 24935807
TI  - Temporal cues and the attentional blink: a further examination of the role of
      expectancy in sequential object perception.
AB  - Although perception is typically constrained by limits in available processing
      resources, these constraints can be overcome if information about environmental
      properties, such as the spatial location or expected onset time of an object, can
      be used to direct resources to particular sensory inputs. In this work, we
      examined these temporal expectancy effects in greater detail in the context of
      the attentional blink (AB), in which identification of the second of two targets
      is impaired when the targets are separated by less than about half a second. We
      replicated previous results showing that presenting information about the
      expected onset time of the second target can overcome the AB. Uniquely, we also
      showed that information about expected onset (a) reduces susceptibility to
      distraction, (b) can be derived from salient temporal consistencies in
      intertarget intervals across exposures, and (c) is more effective when presented
      consistently rather than intermittently, along with trials that do not contain
      expectancy information. These results imply that temporal expectancy can benefit
      object processing at perceptual and postperceptual stages, and that participants
      are capable of flexibly encoding consistent timing information about
      environmental events in order to aid perception.

PMID- 24935808
TI  - Feature-based inattentional blindness: loss of awareness to featural information
      in fully attended objects.
AB  - In two experiments, we investigated the impact of feature-based attention on
      observers' awareness of object appearance. Participants were shown a sequence of
      two displays, each containing eight objects (rectangles), and were asked to
      detect changes in the orientation of a cued rectangle. A set of baseline trials
      preceded probe trials in which half of the rectangles in each display were
      unexpectedly distorted by 70 %. Participants in both Experiment 1 (100-ms display
      duration) and Experiment 2 (100- and 400-ms display durations) were unaware of
      these modifications in the task-irrelevant feature (texture), even when they were
      asked to select the viewed object in a forced choice procedure. A control
      experiment showed that participants could identify the physical distortion when
      they were made aware of its presence. The results demonstrate that feature-based
      attention moderates the appearance of objects, even when those objects are fully
      expected and fully attended, implying a distinct form of unawareness that we term
      feature-based inattentional blindness.

PMID- 24935809
TI  - Working memory resources are shared across sensory modalities.
AB  - A common assumption in the working memory literature is that the visual and
      auditory modalities have separate and independent memory stores. Recent evidence
      on visual working memory has suggested that resources are shared between
      representations, and that the precision of representations sets the limit for
      memory performance. We tested whether memory resources are also shared across
      sensory modalities. Memory precision for two visual (spatial frequency and
      orientation) and two auditory (pitch and tone duration) features was measured
      separately for each feature and for all possible feature combinations. Thus, only
      the memory load was varied, from one to four features, while keeping the stimuli
      similar. In Experiment 1, two gratings and two tones-both containing two varying
      features-were presented simultaneously. In Experiment 2, two gratings and two
      tones-each containing only one varying feature-were presented sequentially. The
      memory precision (delayed discrimination threshold) for a single feature was
      close to the perceptual threshold. However, as the number of features to be
      remembered was increased, the discrimination thresholds increased more than
      twofold. Importantly, the decrease in memory precision did not depend on the
      modality of the other feature(s), or on whether the features were in the same or
      in separate objects. Hence, simultaneously storing one visual and one auditory
      feature had an effect on memory precision equal to those of simultaneously
      storing two visual or two auditory features. The results show that working memory
      is limited by the precision of the stored representations, and that working
      memory can be described as a resource pool that is shared across modalities. 

PMID- 24935810
TI  - Object-centered orienting and IOR.
AB  - Three recent studies reported retinotopic (eye-centered) and object-centered
      attentional facilitation following exogenous cuing in dynamic displays. The
      present study replicates this finding and shows, under the very same experimental
      conditions, inhibition of return (IOR) in both retinotopic and object-centered
      reference frames. Unlike in previous findings, we show that when a single object
      is present in the display, IOR is bound to both retinotopic and object-centered
      locations, defined as a specific location within the boundaries of a single
      object. 

PMID- 24935811
TI  - Characteristics and outcomes of older persons attending the emergency department:
      a retrospective cohort study.
AB  - BACKGROUND: The analysis of routinely collected hospital data informs the design
      of specialist services for at-risk older people. AIM: Describe the outcomes of a
      cohort of older emergency department (ED) attendees and identify predictors of
      these outcomes. DESIGN: retrospective cohort study. METHODS: All patients aged 65
      years or older attending an urban university hospital ED in January 2012 were
      included (N = 550). Outcomes were retrospectively followed for 12 months.
      Statistical analyses were based on multivariate binary logistic regression models
      and classification trees. RESULTS: Of N = 550, 40.5% spent <=6 h in the ED, but
      the proportion was 22.4% among those older than 81 years and not presenting with
      musculoskeletal problems/fractures. N = 349 (63.5%) were admitted from the ED. A
      significant multivariate predictor of in-hospital mortality was Charlson
      comorbidity index [CCI; odds ratio = 1.19, 95% confidence interval: 1.07, 1.34, P
      = 0.002]. Among patients who were discharged from ED without admission or after
      their first in-patient admission (N = 499), 232 (46.5%) re-attended ED within 1
      year, with CCI being the best predictor of re-attendance (CCI <= 4: 25.8%, CCI >
      5: 60.4%). Among N = 499, 34 (6.8%) had died after 1 year of initial ED
      presentation. The subgroup (N = 114) with the highest mortality (17.5%) was
      composed by those aged >77 years and brought in by ambulance on initial
      presentation. CONCLUSIONS: Advanced age and comorbidity are important drivers of
      outcomes among older ED attendees. There is a need to embed specialist geriatric
      services within frontline services to make them more gerontologically attuned.
      Our results predate the opening of an acute medical unit with specialist
      geriatric input.

PMID- 24935812
TI  - The Association of Physicians launches new summer research studentships for
      medical undergraduates.

PMID- 24935813
TI  - Immunohistological expression of human beta-defensin-1 and human beta-defensin-2
      in exacerbation of acute and secondary chronic osteomyelitis of the mandible.
AB  - BACKGROUND: The majority of patients diagnosed with osteomyelitis of the jaw have
      severe complaints. Unfortunately, the pathogenesis still remains unclear. Human
      beta-defensins expressed in epithelial and bone tissues as a part of the innate
      immunity may be involved in disease development. In this study, we hypothesize
      that expression levels of human beta-defensin-1 and -2 in the acute and secondary
      chronic osteomyelitis may be altered in comparison with healthy bone and with
      bisphosphonate-associated necrosis as well as irradiation from a previous study.
      METHODS: Bone samples were collected during surgical debridement in a total of
      eight patients suffering from acute or secondary chronic osteomyelitis of the
      jaw. Expression levels of hBD-1 and -2 were quantified and related to non-stained
      cells. Ratios were compared by one-way ANOVA and multiple tests by Holm
      Bonferroni. RESULTS: Multiple testing revealed no significant differences for
      expression levels of human beta-defensin-1 between all groups, whereas labeling
      index of human beta-defensin-2 was significantly different between specimens of
      bisphosphonate-associated osteonecrosis of the jaws and all other groups. No
      significant difference occurred between samples of floride osteomyelitis and
      healthy bone for expression of hBD-1 and -2. CONCLUSIONS: Although the affected
      patients showed all clinical signs of acute inflammation, expression levels in
      acute and secondary chronic osteomyelitis in the jaws did not reveal
      statistically significant differences compared with healthy bone samples. The
      weak immunological host response in terms of a putative genetically
      predisposition should be further discussed as pathogenesis factor for
      osteomyelitis in the future.

PMID- 24935814
TI  - Possible intermediates of Cu(phen)-catalyzed C-O cross-coupling of phenol with an
      aryl bromide by in situ ESI-MS and EPR studies.
AB  - The C-O coupling reaction between 2,4-dimethylphenol and 4-bromotoluene catalyzed
      by the CuI/K2CO3/phen system can be inhibited by the radical scavenger cumene.
      Complexes [Cu(i)(phen)(1-(2,4-dimethylphenoxy)-4-methylbenzene)](+) (denoted as
      A), {H[Cu(i)(phen)(2,4-dimethylphenoxy)]}(+) and [Cu(i)(2,4-dimethylphenoxy)2](-)
      (denoted as B) were observed by in situ electrospray ionization mass spectrometry
      (ESI-MS) analysis of the copper(i)-catalyzed C-O coupling reaction under the
      catalytic reaction conditions indicating that they could be intermediates in the
      reaction. The in situ EPR study of the reaction solution detected the Cu(ii)
      species with a fitted g value of 2.188. A catalytic cycle with a single electron
      transfer (SET) step was proposed based on these observations. 

PMID- 24935815
TI  - Use of in situ hybridization for HPV in head and neck tumors: experience from a
      national reference laboratory.
AB  - The human papillomavirus (HPV) status of head and neck squamous cell carcinomas
      (SCCs) is a frequent request for Anatomic Pathology labs. However, prognostic
      value of HPV status is limited to identification of high risk HPV in
      oropharyngeal SCCs. The purpose of this study is to investigate the ordering
      practices of in situ hybridization (ISH) for HPV in head and neck tissues at our
      national reference laboratory. All testing orders for low risk, high risk, and
      combined low and high risk HPV-ISH tests requested at ARUP Laboratories between
      January 2010 and November 2013 had their results reviewed and were grouped by
      anatomic location of the tested tissue. The H&E and HPV-ISH slides from a sample
      of the most recent 123 tests were reviewed by two pathologists. A total of 1,128
      HPV-ISH tests were ordered during the study period. Testing for combined low and
      high risk HPV was the most commonly ordered test. The positivity rate for high
      risk HPV was highest in oropharyngeal tissues. 49 of 123 reviewed cases had
      testing requested on non-malignant tissue, 11 of which were non-neoplastic.
      Unnecessary HPV-ISH ordering is prevalent in head and neck tissues. Dual testing
      for low and high risk HPV, frequent testing outside of the oropharynx, and
      testing non-neoplastic tissues appear to be common practices. 

PMID- 24935816
TI  - Investigation of 10 herbicides in surface waters of a horticultural production
      catchment in southeastern Australia.
AB  - Herbicides are regularly applied in horticultural production systems and may
      migrate off-site, potentially posing an ecological risk to surface waterways.
      However, few studies have investigated the levels and potential ecotoxicological
      impact of herbicides in horticultural catchments in southern Australia. This
      study investigated the presence of 10 herbicides at 18 sites during a 5-month
      period in horticulturally important areas of the Yarra Valley in southeastern
      Australia. Seven of the 10 herbicides were detected in the streams, in 39 % of
      spot water samples, in 25 % of surface sediment samples, and in >70 % of the
      passive sampler systems deployed. Few samples contained residues of >=2
      herbicides. Simazine was the herbicide most frequently detected in water,
      sediment, and passive sampler samples and had the highest concentrations in water
      (0.67 MUg/L) and sediment (260 MUg/kg dry weight). Generally the concentrations
      of the herbicides detected were several orders of magnitude lower than reported
      ecotoxicological effect values, including those for aquatic plants and algae,
      suggesting that concentrations of individual chemicals in the catchment were
      unlikely to pose an ecological risk. However, little is known about the combined
      effects of simultaneous, low-level exposure of multiple herbicides of the same
      mode of action on Australian aquatic organisms nor their contribution when found
      in mixtures with other pesticides. Further research is required to adequately
      assess the risk of pesticides in Victorian aquatic environments. 

PMID- 24935817
TI  - Regional disturbances in blood flow and metabolism in equine limb wound healing
      with formation of exuberant granulation tissue.
AB  - As in other fibroproliferative disorders, hypoxia has been suggested to play a
      key role in the pathogenesis of exuberant granulation tissue (EGT). The purpose
      of this study was to investigate metabolism and blood flow locally in full
      thickness wounds healing with (limb wounds) and without (body wounds) formation
      of EGT. Microdialysis was used to recover endogenous metabolites from the wounds,
      and laser Doppler flowmetry was used to measure blood flow. Measurements were
      performed before wounding and 1-28 days after wounding. Blood flow was
      consistently lower in limb wounds than in body wounds throughout the study period
      with no change over time. After wounding and throughout the study period, the
      glucose concentration was significantly lower in limb wounds than in body wounds,
      whereas the lactate level showed a significantly higher concentration in limb
      wounds. The lactate/glucose ratio displayed a significant difference between body
      and limb wounds. In conclusion, the metabolic disturbances may suggest an
      inadequate oxygen supply during the wound healing process in equine limb wounds
      healing with EGT. This may be related to the inherently decreased perfusion in
      the wound bed of limb wounds. 

PMID- 24935819
TI  - Exploring genetic variants predisposing to diabetes mellitus and their
      association with indicators of socioeconomic status.
AB  - BACKGROUND: The relevance of disease-related genetic variants for the explanation
      of social inequalities in complex diseases is unclear and empirical analyses are
      largely missing. The aim of our study was to examine whether genetic variants
      predisposing to diabetes mellitus are associated with socioeconomic status in a
      population-based cohort. METHODS: We genotyped 11 selected diabetes-related
      single nucleotide polymorphisms in 4655 participants (age 45-75 years) of the
      Heinz Nixdorf Recall study. Diabetes status was self-reported or defined by blood
      glucose levels. Education, income and paternal occupation were assessed as
      indicators of socioeconomic status. Multiple regression analyses were used to
      examine the association of socioeconomic status and diabetes by estimating sex
      specific and age-adjusted prevalence ratios and their corresponding 95%
      confidence intervals. To explore the relationship between individual single
      nucleotide polymorphisms and socioeconomic status sex- and age-adjusted odds
      ratios were computed. We adjusted the alpha-level for multiple testing of 11
      single nucleotide polymorphisms using Bonferroni's method (alpha(BF) ~ 0.005). In
      addition, we explored the association of a genetic risk score with socioeconomic
      status. RESULTS: Social inequalities in diabetes were observed for all indicators
      of socioeconomic status. However, there were no significant associations between
      individual diabetes-related risk alleles and socioeconomic status with odds
      ratios ranging from 0.87 to 1.23. Similarly, the genetic risk score analysis
      revealed no evidence for an association. CONCLUSIONS: Our data provide no
      evidence for an association between 11 diabetes-related risk alleles and
      different indicators of socioeconomic status in a population-based cohort,
      suggesting that the explored genetic variants do not contribute to health
      inequalities in diabetes.

PMID- 24935820
TI  - Computational validation of the motor contribution to speech perception.
AB  - Action perception and recognition are core abilities fundamental for human social
      interaction. A parieto-frontal network (the mirror neuron system) matches
      visually presented biological motion information onto observers' motor
      representations. This process of matching the actions of others onto our own
      sensorimotor repertoire is thought to be important for action recognition,
      providing a non-mediated "motor perception" based on a bidirectional flow of
      information along the mirror parieto-frontal circuits. State-of-the-art machine
      learning strategies for hand action identification have shown better performances
      when sensorimotor data, as opposed to visual information only, are available
      during learning. As speech is a particular type of action (with acoustic
      targets), it is expected to activate a mirror neuron mechanism. Indeed, in speech
      perception, motor centers have been shown to be causally involved in the
      discrimination of speech sounds. In this paper, we review recent
      neurophysiological and machine learning-based studies showing (a) the specific
      contribution of the motor system to speech perception and (b) that automatic
      phone recognition is significantly improved when motor data are used during
      training of classifiers (as opposed to learning from purely auditory data). 

PMID- 24935821
TI  - Program directors in their role as leaders of teaching teams in residency
      training.
AB  - BACKGROUND: Program directors have a formal leading position within a teaching
      team. It is not clear how program directors fulfill their leadership role in
      practice. In this interview study we aim to explore the role of the program
      director as strategic leader, based on the research-question: What are the
      experiences of program directors with strategic leadership? METHOD: We conducted
      an interview study using the principles of phenomenography to explore program
      directors' experiences. In the period June 2012-May 2013, 16 program directors
      from different hospital organisations were invited to participate in an interview
      study. Iterative data collection and analysis were based on strategic leadership:
      (1) developing collective mindset, (2) focusing on collaborative learning and (3)
      designing teaching organisation. RESULTS: Fourteen program directors participated
      in this study. We identified four leadership profiles: (1) captains, (2) carers,
      (3) professionals and (4) team-players. The 'team-players' come closest to
      integrally applying strategic leadership. For all four profiles there seems to be
      a preference for developing collectivity by means of providing information.
      Program directors have less experience with promoting collaborative learning and
      the designing of teaching organisation is task-oriented. CONCLUSION: Promoting
      collaborative learning is the most important challenge for developing leadership
      within the teaching team.

PMID- 24935818
TI  - T1rho MRI of human musculoskeletal system.
AB  - Magnetic resonance imaging (MRI) offers the direct visualization of the human
      musculoskeletal (MSK) system, especially all diarthrodial tissues including
      cartilage, bone, menisci, ligaments, tendon, hip, synovium, etc. Conventional MRI
      techniques based on T1 - and T2 -weighted, proton density (PD) contrast are
      inconclusive in quantifying early biochemically degenerative changes in MSK
      system in general and articular cartilage in particular. In recent years,
      quantitative MR parameter mapping techniques have been used to quantify the
      biochemical changes in articular cartilage, with a special emphasis on evaluating
      joint injury, cartilage degeneration, and soft tissue repair. In this article we
      focus on cartilage biochemical composition, basic principles of T1rho MRI,
      implementation of T1rho pulse sequences, biochemical validation, and summarize
      the potential applications of the T1rho MRI technique in MSK diseases including
      osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint
      repair. Finally, we also review the potential advantages, challenges, and future
      prospects of T1rho MRI for widespread clinical translation.

PMID- 24935822
TI  - Applicability and agreement of different diagnostic criteria for sarcopenia
      estimation in the elderly.
AB  - The purpose of this study cross-sectional study comprising 132 community dwelling
      elderly (>= 60 years) was to identify sarcopenia prevalence in the Brazilian
      elderly, utilizing different diagnostic criteria and analyze agreement between
      criteria. Sarcopenia was assessed by nine muscle mass diagnostic criteria, by two
      muscle strength criteria and also by the combination of criteria. Prevalence was
      analyzed for each method, along with differences by gender and age group through
      calculation of the prevalence ratio (PR) and confidence interval (CI) 95%. The
      Kappa coefficient was used to analyze the level of agreement between all
      criteria. Sarcopenia prevalence varied between 60.6% and 8.3% with the
      application of muscle mass criteria, and between 54.2% and 48.8% with the
      application of strength criteria. The combination muscle mass+strength resulted
      in a decrease of prevalence in all criteria, varying between 36.6% and 6.1%.
      There was an increase in prevalence according to age groups for all methods.
      Prevalence was higher for men according to three muscle mass criteria, and higher
      in women for strength criteria and by two combined mass+strength criteria. The
      best level of agreement was obtained for two methods that utilized dual energy X
      ray absorptiometry (DXA). The prevalence of sarcopenia differs by gender and age
      and definition criteria. The low agreement levels obtained between methods and
      the different prevalence values encountered indicate the necessities of an
      operational definition for the estimation of sarcopenia in different population.

PMID- 24935824
TI  - Statistical analysis with missing exposure data measured by proxy respondents: a
      misclassification problem within a missing-data problem.
AB  - In studies of older adults, researchers often recruit proxy respondents, such as
      relatives or caregivers, when study participants cannot provide self-reports
      (e.g., because of illness). Proxies are usually only sought to report on behalf
      of participants with missing self-reports; thus, either a participant self-report
      or proxy report, but not both, is available for each participant. Furthermore,
      the missing-data mechanism for participant self-reports is not identifiable and
      may be nonignorable. When exposures are binary and participant self-reports are
      conceptualized as the gold standard, substituting error-prone proxy reports for
      missing participant self-reports may produce biased estimates of outcome means.
      Researchers can handle this data structure by treating the problem as one of
      misclassification within the stratum of participants with missing self-reports.
      Most methods for addressing exposure misclassification require validation data,
      replicate data, or an assumption of nondifferential misclassification; other
      methods may result in an exposure misclassification model that is incompatible
      with the analysis model. We propose a model that makes none of the aforementioned
      requirements and still preserves model compatibility. Two user-specified tuning
      parameters encode the exposure misclassification model. Two proposed approaches
      estimate outcome means standardized for (potentially) high-dimensional covariates
      using multiple imputation followed by propensity score methods. The first method
      is parametric and uses maximum likelihood to estimate the exposure
      misclassification model (i.e., the imputation model) and the propensity score
      model (i.e., the analysis model); the second method is nonparametric and uses
      boosted classification and regression trees to estimate both models. We apply
      both methods to a study of elderly hip fracture patients.

PMID- 24935825
TI  - Investigation of the coal fly ashes using IR spectroscopy.
AB  - The results of FT-IR spectroscopic studies of coal fly ashes, originated from
      various polish power plants are reported. The results of MIR investigations were
      compared to the X-ray diffraction (XRD) measurements and chemical analyses. They
      are mainly composed of silica, alumina and lime. The infrared spectrum in the
      middle range can be used to describe both the structure of phases present in the
      fly ash and to identify the characteristic elements of the individual components
      of ash. The results indicate that the amount of aluminosilicate and its Si/Al
      ratio induce a shift in the T-O stretching band appearing at 950-1100 cm(-1).
      Moreover, FWHM of these bands indicates the participation of the crystalline
      phase relative to amorphous. The presence of carbonate phases generates
      substantial changes in the 1450-1400 cm(-1) area of the spectra. The presence of
      such phases as anhydrite, mullite or illite has also been established on the
      basis of IR spectra.

PMID- 24935823
TI  - The impact of body mass index on renal functional outcomes following minimally
      invasive partial nephrectomy.
AB  - OBJECTIVE: To assess the impact of body mass index (BMI) on perioperative and
      renal functional outcomes in patients undergoing minimally invasive partial
      nephrectomy (MIPN). MATERIALS AND METHODS: In our IRB-approved, prospectively
      maintained clinical database, we identified 1206 patients who underwent kidney
      surgery from 2002 to 2013. Estimated glomerular filtration rate (eGFR) was
      obtained at baseline and each follow-up visit. From this group, patients who
      underwent MIPN with more than 12 months of follow-up were selected. Patients were
      separated into 4 cohorts based on BMI: normal weight (<25 kg/m(2)), preobese (25
      30 kg/m(2)), obese class 1 (30-35 kg/m(2)), and obese class >=2 (>35 kg/m(2)).
      Change in eGFR was compared across demographic and clinical variables through
      linear and logistic regression models. RESULTS: A total of 235 patients met
      inclusion criteria with median follow-up of 29 months (interquartile range [IQR]
      19, 45). There were no differences in demographic, perioperative, or pathologic
      features between BMI groups. While controlling for gender, race, Charlson
      comorbidity score, tumor size, and ischemia time, obese class 1 (odds ratio [OR]
      4.68, p=0.019), obese class >=2 (OR 4.27, p=0.033), and age (OR 1.06, p=0.014)
      were associated with increased risk of CKD stage >=3; however, higher baseline
      eGFR (OR 0.91, p<0.001) was associated with a reduced risk of CKD stage >=3.
      While controlling for the same variables, increasing BMI was associated with a
      significant absolute reduction in eGFR at 1 year (0.38 mL/minute/1.73 m(2)
      reduction in GFR per 1 kg/m(2) increase in BMI, p=0.009). CONCLUSIONS: MIPN is
      technically feasible in obese patients with similar perioperative outcomes to
      nonobese patients. BMI is an independent risk factor for worsening kidney
      function following MIPN.

PMID- 24935826
TI  - Infrared, Raman and NMR spectra, conformational stability and vibrational
      assignment of 7,8-Dihydroxy-4-Methylcoumarin.
AB  - We report a combined some (infrared, Raman and NMR) spectroscopic and quantum
      chemistry study on 7,8-Dihydroxy-4-Methylcoumarin molecule (78D4MC). The Raman
      and IR spectra of 78D4MC molecule were recorded and analyzed in the region 3500
      50 cm(-1) and 4000-400 cm(-1), respectively. Potential energy scans were
      performed at the MMFF level of theory. All possible conformers, which are results
      at the MMFF level theory, were re-computed at the B3LYP functional with cc-pVDZ
      basis set. The optimized geometrical parameters, harmonic vibrational wavenumbers
      and NMR chemical shifts of the most stable conformer were calculated at the
      B3LYP/6-311G(d,p), cc-pVTZ and cc-pVQZ level in the proximity of the isolated
      molecule. DFT calculations were combined with Pulay's scaled quantum mechanics
      force field (SQMFF) methodology in order to fit the theoretical wavenumbers to
      the experimental ones.

PMID- 24935827
TI  - Twist technique for removal of spinal extradural arachnoid cyst: technical note.
AB  - STUDY DESIGN: We document a spinal extradual arachnoid cyst treated by twist
      technique. The cyst is tightly adherent to the neural tissue or the dura, and the
      communication stalk is little or short. OBJECTIVE: To demonstrate the
      effectiveness of twist technique of closure of the communication stalk for the
      removal of spinal extradural arachnoid cyst. The standard treatment for a spinal
      extradural arachnoid cyst is complete excision of the cyst, followed by
      obliteration of the communication stalk and repair of the dural defect. To our
      knowledge, twist technique of the communication stalk for removal of spinal
      extradural arachnoid cyst has not been reported. METHODS: A 44-year-old woman
      presented with a 10-year history of pain and dysesthesia, initially in the
      posterior neck region and extending gradually to the distal portion of the right
      upper extremity. Pain and dysesthesia were exaggerated when she was lying down
      and relieved when standing or walking. She was diagnosed with an extradural
      arachnid cyst ranging from spinal regions T1 to T3 using MRI. Computerized
      tomography myelography revealed a mass located posterior to the spinal cord.
      Pooling of contrast medium was observed in the lesion indicating communication
      with the subarachnoid space. Laminectomy of the T1-T3 region was performed,
      preserving the spinous processes and the facet joints. A short communication
      stalk was found at the proximal root sleeve of right T3. This stalk was closed
      using twist technique. RESULTS: The patient experienced marked reduction of pain
      and dysesthesia after surgery, and the headache and blurred vision completely
      disappeared. Five days after the operation, she was discharged home in good
      condition. Postoperative 1 year later, the patient had completely recovered and
      resumed her normal life. CONCLUSIONS: Twist technique can be seen safe and
      effective as another surgical option for spinal extradural arachnoid cysts
      containing a short stalk and dense fibrous adhesion with the dura mater.

PMID- 24935830
TI  - [The effect of fluoride on the metabolism of teeth and bone in rats].
AB  - PURPOSE: To investigate the effect of fluoride on the metabolism of teeth and
      bone in rats, and to probe the mechanism of pathogenesis of dental fluorosis.
      METHODS: A total of 48 Wistar rats were randomly and equally divided into 4
      groups including control group (distilled water), low-dose group(NaF,50 mg/L),
      medium-dose group (NaF,100 mg/L) and high-dose group (NaF, 150 mg/L). After 8
      weeks, the rats were sacrificed under anesthesia, and serums were collected. The
      biochemical technique was used to test serum calcium. Changes in the fluorine
      content in serums and teeth of each group were analyzed with fluoride ion
      selective electrode method. Radioimmunoassay was employed to detect the levels of
      osteocalcin (OC), parathormone (PTH) and calcitonin (CT), respectively. SPSS13.0
      software package was used for statistical analysis. RESULTS: The fluorine content
      in serum and teeth in the fluoride group were significantly higher than that of
      the control group (P<0.05), and increased with the increasing concentrations (F
      value was 11.234 and 275.148 respectively, P<0.01). The level of calcium in serum
      (F=3.906, P<0.05) in the fluoride group was significantly lower than in the
      control group. The level of PTH and OC in serum in medium and high-dose group
      were significantly higher than in the control group (P<0.01), with the level of
      CT in high-dose group decreased significantly (P<0.01). The differences of the
      level of OC, PTH, CT between groups were significant (F value was 8.548, 3.801
      and 5.121 respectively, P<0.05). CONCLUSIONS: Fluoride affects the metabolism of
      teeth and bone in rats and OC, PTH, CT plays a key role in the pathogenesis of
      dental fluorosis.

PMID- 24935829
TI  - Has overweight any influence on the effectiveness of conservative treatment in
      patients with low back pain?
AB  - PURPOSE: Low back pain and overweight are two relevant disabling health
      conditions. To date, there is a lack of information about the effectiveness of
      nonoperative therapy in persons with overweight and low back pain. The aim of our
      study was to evaluate if overweight has any influence on the effectivity of
      conservative treatment in patients with low back pain during a mid- to long-term
      time period. METHODS: 128 patients with low back pain participated in this study.
      All of them got an inpatient conservative treatment program. The weight status
      was classified according to the body mass index (BMI) in three weight groups
      (normal, overweight, obesity). The patients were asked to fill out a standardized
      questionnaire regarding self-reported pain with the visual analog scale and their
      disability with the Oswestry Disability Index and the Roland-Morris Disability
      Questionnaire at four time points (beginning and end of hospital stay and after 5
      and 17 months). RESULTS: Concerning the short-term results of the three scores,
      we always observed an improvement of the patients' condition with statistically
      significant reduction of pain and disability at discharge. This was true for the
      total collective as well as for each of the three BMI-groups when considered
      separately. The pain intensity and disability were still and mostly statistically
      significantly decreased in the mid- to long-term follow-up. Regarding the three
      BMI-groups among themselves, the differences of the data in the pain and
      disability scores showed generally no statistical significance. CONCLUSIONS: We
      conclude for the first time that a conservative treatment program in patients
      even with chronic low back pain is effective both in a short-term and a mid- to
      long-term time period respectively without any significant differences between
      patients with a normal BMI or with overweight or obesity.

PMID- 24935831
TI  - [Study on gene vaccine pcDNA3-PAc against dental caries by intranasal
      immunization in rabbits].
AB  - PURPOSE: To investigate the efficiency of pcDNA3-PAc on Japanese long-eared white
      rabbits by intranasal immunization, and observe the appreciate gene vaccine dose
      in rabbit immunization. METHODS: Thirty Japanese long-eared white rabbits were
      randomly divided into 5 groups (6 in each group) as follows: 200, 400, 600 MUg
      pcDNA3-PAc plasmid group; 400 MUg pcDNA3 group and inactivated whole-cell vaccine
      positive control group. The rabbits were immunized twice, and plasmid groups and
      whole-cell group were coupled Freund's adjuvant with 1:1 ratio. The specific IgG
      and S-IgA antibodies in serum and saliva were detected with indirect ELISA
      method. The data was analyzed with SPSS 17.0 software package. RESULTS: (1) The
      peak time of the antibodies appeared between 8-10 weeks after the first
      immunization; (2)The specific antibodies IgG and S-IgA could be detected 2 weeks
      after immunization;(3)The level of salivary specific S-IgA and serum specific IgG
      of pcDNA3-PAc were significantly higher than negative groups (P<0.05). The titer
      of the 200 MUg was significantly lower than those of 400 MUg and 600 MUg group
      (P<0.05). CONCLUSIONS: (1)The recombinant plasmid pcDNA3-PAc has immunogenicity,
      which can induce specific immune responses for 14 weeks in rabbits. (2)The
      results of the present study show that 200 MUg, 400 MUg and 600 MUg are effective
      immunizational dosage to 1.5 kg Japanese long-eared white rabbits. (3)400 MUg and
      600 MUg pcDNA3-PAc can be considered as the optimal dosage than 200 MUg at
      present experimental condition. Supported by Guizhou Science and Technology
      Projet of Distinguished Young Talents [2005(0509)], Guizhou College and
      University Leading Academic Discipline Project [2012(15)] and Zunyi Medical
      University Project of Distinguished Research Team [2012(12)].

PMID- 24935832
TI  - [Expression of HIF-1alpha in the genioglossus associated with induced bilateral
      intermittent nasal obstruction in young rats].
AB  - PURPOSE: To investigate the expression of HIF-1alpha in the genioglossus
      associated with induced bilateral intermittent nasal obstruction in young rats.
      METHODS: Thirty 4-week-old SD rats were employed and equally divided into 3
      groups. In group A, both nostrils were occluded by nose plugs. In group B, the
      right nostril was occluded. In group C, no obstruction of the nose was performed
      as control group. The obstruction time was from 8 am to 12 am everyday, and the
      period was 21 d and 55 d. The genioglossus was taken for HE, and
      immunohistochemical staining was used to detect the expression of HIF-1alpha. The
      data was analyzed with SPSS 13.0 software package. RESULTS: The rats were
      sacrificed at the 21th day and 55th day, respectively. The expression of HIF
      1alpha in group A was significantly higher than that in group B and group C, and
      became stronger with the increasing of obstruction time. CONCLUSIONS: Oral
      breathing caused by bilateral intermittent nasal obstruction in young rats
      results in overexpression of HIF-1alpha in the genioglossus. Supported by
      Research Fund and Experimental Animal Fund of Science and Technology Committee of
      Shanghai Municipality (11140902001).

PMID- 24935833
TI  - [Comparative study of sensitivity of different dental metal materials].
AB  - PURPOSE: To compare the sensitivity of different dental metal materials, in order
      to provide references for choosing of dental metal materials. METHODS: Patch test
      was performed on 92 patients wearing dental metal prosthesis. Pearson Chi-square
      test, corrected Chi-square test and Fisher exact test were used for statistical
      analysis with SPSS17.0 software package. RESULTS: (1)The sensitivity rates of
      different metal materials were different. The allergy rate of nickel (Ni) was the
      highest (22.8%), while the allergy rate of aluminum (Al) was 0. (2)More women
      were allergic to both palladium (Pd) and nickel (Ni) than men with significant
      difference (P>0.05). (3)Women with ear piercing were more allergic to nickel
      (Ni), but there was no significant correlation between ear piercing and nickel
      allergy (P>0.05).(4)There was cross reaction between nickel(Ni)and palladium
      (Pd), 83.3% of palladium (Pd) allergy patients were allergic to nickel (Ni),
      while 47.6% of nickel(Ni) allergy patients were allergic to palladium (Pd).
      (5)Patch test had a delayed reaction. CONCLUSIONS: Dental metal materials have
      certain allergies, women are more allergic to both palladium (Pd) and nickel (Ni)
      than men, with significant difference. Patch test may have a delayed reaction. If
      necessary, observation for 96 h, 7 days or even longer time, are needed to
      exclude false positivity. Supported by Research Fund of Science and Technology
      Committee of Shanghai Municipality (10411950900).

PMID- 24935834
TI  - [The influence of drilling pulling ways and cooling systems on dental implant
      surgery].
AB  - PURPOSE: To study the effect of different ways of pulling the drilling burs and
      cooling systems on alveolar bone temperature of the surgical area, and explore
      the changes of temperature field in dental implants. METHODS: Forty-eight unified
      standard artificial (nylon) bone blocks were fabricated and divided into 6 groups
      according to different drilling pulling ways and cooling systems. The changes of
      bone temperature field were detected in 6 groups, and the highest temperature in
      temperature field was measured and recorded. The date was analyzed with SPSS 12.0
      software package for ANOVA. RESULTS: The temperature in the surgical area using
      internal cooling systems under the same drilling pulling was lower than using
      external cooling systems. The temperature in the surgical area using secondary
      drilling pulling way was lower than using direct drilling methods under the same
      cooling systems. The temperature in the surgical area using secondary drilling
      pulling way was the lowest when internal cooling systems was adopted(P<0.05).
      CONCLUSIONS: Drilling pulling way and internal cooling systems can effectively
      reduce the temperature in the surgical area, lessen heat production and improve
      the success rate of dental implants.

PMID- 24935835
TI  - [Comparison of expression of transforming growth factor-beta1 in rat dental pulp
      during direct pulp capping with 2 capping agents].
AB  - PURPOSE: To examine and compare the expression of transforming growth factor
      beta1(TGF-beta1) in rat dental pulp after direct pulp capping with calcium
      hydroxide (CH) and mineral trioxide aggregate (MTA). METHODS: The model of direct
      dental pulp capping after first molars was established in 28 female Wistar rats
      with CH and MTA. The rats were sacrificed 1, 3, 5, 7, 14,21 and 28 days after
      direct pulp capping. TGF-beta1 expression in pulp tissues were measured with
      immunohistochemical staining. The data was analyzed by Dunnett t test and paired
      t test with SPSS 13.0 software package. RESULTS: The results showed that no TGF
      beta1 expression was detected in the control group. After direct pulp capping
      with MTA, TGF-beta1 expression gradually increased and reached peak expression on
      5 day. TGF-beta1 expression gradually decreased afterwards and reached normal on
      21 day after direct pulp. TGF-beta1 was mainly expressed in neutrophils,
      odontoblasts cells, vascular endothelial cells and fibroblasts. The expression of
      TGF-beta1 was significantly different between 2 capping agents 1, 3, 5, 7, 14
      days after direct pulp capping (P<0.05). CONCLUSIONS: The results suggest that
      TGF-beta1 expression increases at first and then decreases after direct pulp
      capping. The type of capping agents has an impact on the expression of TGF-beta1
      after direct pulp capping. MTA enhances more TGFbeta-1 expression than CH 1, 3,
      5, 7 and 14 days after direct pulp capping. Supported by Science and Technology
      Plan Project of Liaoning Province (2009225001-2).

PMID- 24935836
TI  - [Finite element stress analysis of all-ceramic continuous crowns of the lower
      anterior teeth in differential shoulder thickness].
AB  - PURPOSE: To investigate the stress distributions under load in 3 types of all
      ceramic continuous crowns of the lower anterior teeth with differential shoulder
      thickness. METHODS: Cone-beam CT (CBCT) was used to scan the in vitro mandibular
      central incisors, and achieve three-dimensional finite element model of all
      ceramic continuous crowns with different shoulder width by using Mimics, Abaqus
      software. Different load conditions were simulated based on this model to study
      the effect of shoulder width variation on finite element analysis of 3 kinds of
      different all-ceramic materials of incisors fixed continuous crowns of the
      mandibular. RESULTS: Using CBCT, Mimics10.01 software and Abaqus 6.11 software,
      three-dimensional finite element model of all-ceramic continuous crowns of the
      mandibular incisor, abutment, periodontal ligament and alveolar bone was
      established. Different ceramic materials and various shoulder width had minor no
      impact on the equivalent stress peak of periodontal membrane, as well as alveolar
      bone. With the same shoulder width and large area of vertical loading of 120 N,
      the tensile stress was the largest in In-Ceram Alumina, followed by In-Ceram
      Zirconia and the minimum was IPS.Empress II. Under large area loading of 120 N 45
      degrees  labially, when the material was IPS.Empress II, with the shoulder width
      increased, the porcelain plate edge of the maximum tensile stress value
      increased, while the other 2 materials had no obvious change. CONCLUSIONS: Finite
      element model has good geometric similarity. In the setting range of this study,
      when the elastic modulus of ceramic materials is bigger, the tensile stress of
      the continuous crown is larger. Supported by Research Project of Department of
      Education, Jiangxi Province (GJJ09130).

PMID- 24935837
TI  - [Quantitative analysis of nFA/PEEK implant interfaces in Beagle dogs].
AB  - PURPOSE: A new synthetic nano-fluorapatite poly-ether-ether-ketone (nFA/PEEK)
      dental implant in screw type was developed and its biocompatibility and
      osseointegration ability were evaluated in Beagle dogs. METHODS: Ten sandblasted
      and 10 non-sandblasted nFA/PEEK implants were placed in 6 adult Beagle dogs and
      the bilateral mandibular second and third premolar was extracted and the wounds
      were healed over 3 months. Three dogs were randomly chosen and executed at the
      end of 8th and 12th week. To evaluated bone to implant contact(BIC) and mineral
      apposition rate(MAR), tetracycline was intramuscularly given twice at 10th and
      3rd day, before sacrifice respectively. The implants and the surrounding bone as
      a whole were collected and examined by synchrotron radiation tomography.
      Undecalcified implant and bone specimens were cut and stained by Van Gieson for a
      static histomorphometric analysis. The data was analyzed using SPSS18.0 software
      package. RESULTS: The implants were demonstrated by synchrotron radiation and
      connected to most of their bone beds at 8th week. Some new bones were developed
      into threads of screw implants, while complete osseointegration were noted at
      12th week. Sandblasted implants were found to be faster matured. BIC and MAR of
      sandblasted group (63.34%, 1.51 MUm/d) were significantly higher than that of non
      sandblasted group (22.97%, 1.34 MUm/d) (P<0.05) at 8th week. BIC of sandblasted
      group (75.49%) was significantly higher than that of non-sandblasted (55.35%)
      (P<0.05) at 12th week, while MAR was not significantly different between the 2
      groups (1.28 MUm/d versus 1.27 MUm/d). The static parameters showed that bone
      volume fraction (BV/TV) and trabecular number (Tb.N) of sandblasted group were
      significantly higher than that of non-sandblasted group, while trabecular spacing
      (Tb.Sp) was significantly lower (P<0.05); No significant difference was found in
      trabecular thickness (Tb.Th) between 2 groups (P>0.05). The sandblasting group
      was more conductive to increase their bone mass. CONCLUSIONS: Sandblasted
      synthetic polymer's biomaterial nFA/PEEK has excellent biocompatibility and
      osteogenic properties, which is better osseointegrated to its bone bed. It will
      be a promising material as dental implants in the future.

PMID- 24935838
TI  - [The effect of vascular endothelial cells on the migration of periodontal
      ligament cells and gingival fibroblasts].
AB  - PURPOSE: To investigate the effect of human vascular endothelial cells (HUVEC) on
      the migration of human periodontal ligament cells (HPDLC) and human gingival
      fibroblasts (HGF) through a model mimicking periodontal wound healing or
      regeneration. METHODS: HUVEC, HPDLC and HGF were co-cultured using a Transwell
      system, while HPDLC or HGF was cultured independently as control. Chemotaxis
      assay was performed using cell culture inserts (0.8MUm pore size) to assess the
      effect of HUVEC on HPDLC and HGF vertical migration at 24h. A scratch wound assay
      was performed to assess the effect of HUVEC on HPDLC and HGF horizontal migration
      at 0 h, 8 h, 16 h and 24 h. A round glass sheet assay was performed to assess the
      effect of HUVEC on HPDLC and HGF wound healing ability at 1d, 4d and 7d. The data
      was processed with SPSS 13.0 software package. RESULTS: At the round glass sheet
      assay, while HUVEC was present, the integrated option density (IOD) of HPDLCs and
      HGFs were significantly higher than each of the single culture (P<0.01). Results
      of chemotaxis assay and scratch wound assay showed that the cell number of HPDLCs
      and HGFs were significantly higher than each of the single culture while HUVEC
      was present (P<0.01), and the number of PHDLCs was significantly higher than HGFs
      on chemotaxis assay (P<0.01) but the result of scratch wound assay was on the
      contrary (P<0.01). CONCLUSIONS: The presence of HUVEC can promote migration of
      periodontal cells, and the effect is more prominent on HPDLC than on HGF in
      vertical migration and wound healing, while horizontal migration is more
      prominent on HGFs as contrast.

PMID- 24935839
TI  - [Preliminary study on root canal morphology of maxillary second molars].
AB  - PURPOSE: To investigate the root canal morphology and anatomy of maxillary second
      molars using transparent tooth technique and cone-beam computed tomography
      (CBCT), and explore the consistency of 2 methods in identifying root canal
      configurations and morphology. METHODS: Fifty extracted maxillary second molars
      were scanned by CBCT and analyzed using assistant software. Root canal
      configurations of each root were identified based on Vertucci's classification
      and recorded. All transparent teeth samples were made with modified root canal
      staining technique, and the root canal configurations of each root were
      classified based on Vertucci's classification. The results were analyzed
      statistically with SPSS17.0 software package. RESULTS: According to transparent
      tooth technique, type I was the most common configuration in distobuccal root and
      palatal root. An additional configuration type 3-2-2 was found in the present
      study, which was not included in Vertucci's classification. The wide variety of
      canal systems was seen in the mesiobuccal root. Type I configuration was most
      prevalent(54.4%), followed by Type II, IV,V,VI. The prevalence of second canal in
      mesiobuccal root (MB2) was 41.3%. The results of canal morphology and
      configuration were consistent between transparent tooth technique and CBCT.
      CONCLUSIONS: Maxillary second molars have the most complex root and canal
      morphology, especially for the mesiobuccal root. For identifying root canal and
      root anatomy, CBCT can be used as an alternative to transparent tooth technique
      in clinical practice. The application of 3D reconstruction based on CBCT helps us
      to visualize the root canal anatomy.

PMID- 24935840
TI  - [The effect of the structure of epithelial root sheath on the development of
      tooth root].
AB  - PURPOSE: To investigate the effect of the structure of epithelial root sheath
      (ERS) on the development of tooth root. METHODS: The first molars of postnatal
      (PN) 8 d SD rats were chosen to harvest the apical tissue. The tissues were
      digested by the mixture of type I collagenase and dispase. One part of the cell
      suspension was pelleted by centrifugalization. The other part of the cell
      suspension was digested by trypsin and then pelleted. The cell pellets were
      cultured in vitro for 4 hours and then implanted into renal capsule of the mother
      rats. RESULTS: It was found that ERS was dissociated into fragments by the
      mixture of type I collagenase and dispase or single cells by trypsin. The pellets
      containing fragments of ERS generated tooth root-like structure and periodontal
      tissues. The pellets containing single cells of ERS formed tubular and bone-like
      dentin. CONCLUSIONS: The bilayered epithelial structure of ERS has important role
      in the development of tooth root.

PMID- 24935841
TI  - [Construction and application of the tissue bank and database of oral mucosa
      precancerous lesions in the Yangtze delta].
AB  - PURPOSE: To construct a database and a tissue bank of oral mucosa precancerous
      lesions and to estimate the application values. METHODS: Patients in the Yangtze
      delta suffering oral mucosa precancerous lesions were enrolled into this study.
      The patients' clinical data and samples of oral precancerous mucosa, salivary and
      blood were collected to create a tissue bank, based on which a database was
      constructed using Microsoft Access software, Brower/Server structure and ASP
      language. RESULTS: The tissue bank and database of oral mucosa precancerous
      lesions were successfully built. The procedure to harvest, store and transport
      the samples had been standardized. The database showed good interactive
      interface, convenient for data collection, query and share in the internet.
      CONCLUSIONS: We constructed the tissue bank and database of oral mucosa
      precancerous lesions for the first time, which not only help preserve the
      biological resource of oral mucosa precancerous lesions, but also provide
      enormous convenience in clinical work, researching and teaching. Supported by
      Research Fund of Science and Technology Committee of Shanghai Municipality
      (08ZR1416700).

PMID- 24935842
TI  - [Fixed orthodontic treatment combined with surgical fenestration in the treatment
      of impacted mandibular first molars].
AB  - PURPOSE: To investigate the treatment of impacted mandibular first molars by
      straight wire appliance technique, and evaluate the effectiveness of treatment.
      METHODS: Eight patients with first mandibular impacted molars were treated with
      MBT straight wire appliance. Surgical fenestration was done after sufficient
      space created. Statistical comparisons were carried out using t test by SPSS 12.0
      software package. RESULTS: Eight mandibular impacted molars were brought into
      occlusal plane (3.94+/-0.49 mm), and the overbite and overjet were normal. Good
      occlusion was achieved. X-ray film showed that alveolar bone growth around the
      molars was good. CONCLUSIONS: Orthodontic treatment combined with surgical
      fenestration can effectively correct the impacted mandibular first molars.
      Supported by Natural Science Foundation of Zhejiang Province (Y2080253).

PMID- 24935843
TI  - [A clinical retrospective analysis of dental implants replaced in previously
      failed sites].
AB  - PURPOSE: To evaluate the clinical outcomes as well as related factors of dental
      implants replaced in previously failed sites. METHODS: A total of 12 patients (15
      implants) who received replacement in previously failed sites during January 2005
      to December 2011 were included. Outcomes of redo-implants were collected and
      clinical data was recorded and analyzed regarding risk factors related to redo
      implants' survival using SPSS13.0 software package. RESULTS: The survival rate of
      redo-implants was 100% [(33.5+/-15.4) months]. The mean redo-implant diameter
      (4.5+/-0.6) mm was significantly larger than the previous one (4.1+/-0.7) mm
      (P<0.05). The mean survival time of implants placed for the first time was
      (12.9+/-15.9) months. Implant replacement occurred (6.8+/-4.4) months after
      original implant removal. No significant influence was observed on patient and
      implant-related factors as well as surgery and prosthesis-dependent factors.
      CONCLUSIONS: Reimplantation in previously failed site is considered as one of
      feasible prosthesis plans, and surgeons ought to get enough confidence to achieve
      satisfactory implant survival rates. Supported by Liaoning Provincial Natural
      Science Foundation (20092093), Liaoning Provincial Science and Technology
      Foundation (2012225090), and Shenyang Science and Technology Foundation (F11-264
      1-25, F12-277-1-18).

PMID- 24935844
TI  - [Pit and fissure sealant for caries prevention in 457 children in Uygur city:
      results of 2-year follow-up].
AB  - PURPOSE: To investigate the 2-year results of pit and fissure sealant in 457
      children in Uygur city for caries prevention in the first permanent molars.
      METHODS: One thousand four hundred and ninety-nine newly erupted first permanent
      molars in 457 children between the ages of 7 and 9 in Uygur city underwent pit
      and fissure sealing using 3M Concisse sealant. The retention of sealants 6, 12
      and 24 months after sealing was observed and the caries occurrence were recorded.
      The data was analyzed with SPSS 16.0 software package. RESULTS: The retention
      rate of pit and fissure sealant 6, 12 and 24 months after sealing was 98.33%,
      92.71% and 88.93%, respectively. The frequency of dental caries was 0%, 0.63% and
      1.15% respectively, which were significantly reduced compared with the average
      prevalence in China (P<0.05). CONCLUSIONS: Pit and fissure sealant is safe and
      effective in preventing dental decay in first permanent molar in Uygur children,
      which is worthy of wide clinical application. Supported by Comprehensive
      Intervention Pilot Project for Pediatric Oral Diseases in Middle and Western Area
      of China in 2010.

PMID- 24935845
TI  - [Evaluation of fiber reinforcement composites in restoring lower dentition defect
      and fixing loose teeth for chronic periodontitis].
AB  - PURPOSE: To evaluate the effect of fiber reinforcement composites (FRC) in
      treating chronic periodontitis with dentition defect. METHODS: Thirty patients
      who had chronic periodontitis and missed less than 2 lower anterior teeth were
      chosen. After appropriate periodontal treatment, EverStick fibers were used to
      fabricate splint with the missing teeth repaired. One month, 6 months, 1 year and
      2 years after treatment, periodontal indexes such as plaque index (PLI), gingival
      index (GI) and probe depth (PD) were recorded and the patients' satisfaction was
      evaluated. SPSS 17.0 software package was used for statistical analysis. RESULTS:
      The results showed that no significant difference was found in PLI and GI during
      observation period (P>0.05). PD decreased significantly after 6 months of
      observation (P<0.05). Patients' satisfaction degree for aesthetics,
      pronunciation, comfort and function was beyond 80%. CONCLUSIONS: Using FRC
      technique in chronic periodontitis with dentition defect can effectively fix the
      loosen teeth and maintain physical function. Appropriate periodontal treatment
      every 6 months is the key factor for satisfactory results.

PMID- 24935846
TI  - [Patients' experiences with the Forsus appliance].
AB  - PURPOSE: To investigate patients' experiences with the Forsus appliance. METHODS:
      This questionnaire survey was focused on patients' comprehensive experiences with
      Forsus, both initially and after several months of wearing, including the
      patients' overall impressions of the appliance. The survey was conducted in 64
      patients wearing Forsus. RESULTS: A high percentage of patients(83.7%) reported
      neutral to favorable experience with Forsus. 85.4% of patients reported gradual
      adaption to the appliance within 4 weeks. Cheek irritation was the most serious
      side effect (about 52%). Cheek irritation and other side effect disappeared over
      time. CONCLUSIONS: The Forsus appliance is relatively well accepted by patients.
      Most patients experience some discomfort and functional limitations at first.
      However, the side effect gradually diminishes with time, and the patients adapt
      to the appliance finally. Practitioners should be especially vigilant about
      problems of cheek irritation.

PMID- 24935847
TI  - [Expression and clinical significance of p53 and autophagy-related gene Beclin1
      in salivary pleomorphic adenoma and carcinoma in pleomorphic adenoma].
AB  - PURPOSE: To investigate the expression of p53 and Beclin1 in salivary pleomorphic
      adenoma (PA) and its clinical significance. METHODS: The expression of p53 and
      Beclin1 were assessed by immunohistochemistry in 108 cases of PA and 20 cases of
      carcinoma in pleomorphic adenoma(CIPA). The results were used to analyze the
      relationship between gene expressions and the development of PA as well as the
      clinical pathological features. Statistic analysis was conducted with SPSS 20.0
      software package. RESULTS: The positive expressions of p53 in PA samples (9%)
      were significantly lower than that in CIPA(14%) (P<0.001). The positive
      expressions of autophagy-related gene Beclin1 in PA samples(91%) were
      significantly higher than that CIPA (11%) (P<0.001). The expression levels of
      these genes were not associated with gender, age, clinical course, tumor size,
      and location of PA(P>0.05). There was a negative correlation between p53 and
      Beclin1 expression in PA (r=-0.330,P<0.05). CONCLUSIONS: The expression levels of
      Beclin1 and p53 protein are closely related to the development of PA. Reduced
      autophagy and enhanced anti apoptosis coexist in the process of tumor formation.
      Thus, raising the autophagy ability may become another alternative choice for
      cancer therapy.

PMID- 24935848
TI  - [Grade IV myelosuppression after induction chemotherapy of TPF on oral cancer:
      clinical analysis of 29 cases].
AB  - PURPOSE: To observe and evaluate the clinical features and treatment strategies
      of IV myelosuppression after induction chemotherapy of oral mucosa squamous cell
      carcinoma under conventional dosage. METHODS: Twenty-nine patients of oral mucosa
      squamous cell carcinoma pathologically diagnosed between 2006 and 2012 were
      enrolled into this study. The patients received induction chemotherapy with
      docetaxel-cisplatin-5-fluorouracil (TPF) and suffered from grade IV
      myelosuppression. Regulations and treatment strategies of the bone marrow
      myelosuppression were analyzed, retrospectively. RESULTS: Twenty-nine cases had
      bone marrow suppression 9-14 days after induction chemotherapy, and the median
      time was 10 days, with a "U"-shaped fluctuation pattern. There were 26 cases with
      colony-stimulating factor(CSF) therapy completing treatment according to the
      schedule and 2 cases were required to radiotherapy because of unsatisfied effect
      of CSF therapy. One case died and the death rate after chemotherapy was 0.68% in
      this group. CONCLUSIONS: The incidence of grade IV myelosuppression is normal and
      fatal. This study shows the starting time of the "U"-shaped fluctuation and the
      necessaries of adding CSF therapy at the same time. The emergency treatment of
      myelosuppression should be used including single disinfected ward mouthwash and
      therapy of CSF drug.

PMID- 24935849
TI  - [Detection of root variations of permanent mandibular first and second molars by
      cone-beam computed tomography].
AB  - PURPOSE: To explore the prevalence and distribution pattern of the root
      variations of permanent mandibular first and second molars in an eastern Chinese
      population. METHODS: Cone-beam computed tomography images were collected
      retrospectively from 261 Chinese patients in Suzhou Stomatological Hospital. The
      incidences of the root variations were determined. The trait frequency
      differences between genders and sides were tested using Chi-square test with SPSS
      13.0 software program. Correlations in the occurrence of the root variations
      between antimeric teeth, as well as between the two types of molars were analyzed
      with Spearman rank correlation test. RESULTS: The incidence of three-rooted
      mandibular molars was 24.7% (108/437) counted by teeth, and 27.9% (56/201)
      counted by individuals. The incidence of the antimeric teeth in both sides was
      66.1% (37/56) and the correlation coefficient was 0.738 (P<0.01). The incidence
      of C-shaped rooted in mandibular second molars was 43.3% (180/416) counted by
      teeth, and 49.7%(96/193) counted by individuals. The bilateral incidence was
      79.2% (76/96) and the correlation coefficient was 0.790 (P<0.01). The incidence
      of the female group was significantly (P<0.05) higher than males. No significant
      correlation was found between the occurrence of three-rooted mandibular first
      molars and group C-shaped toot in mandibular second molars (r=0.033, P>0.05).
      CONCLUSIONS: The prevalence of three-rooted mandibular first molars and C-shaped
      root in mandibular second molars are high in the eastern Chinese population.
      Understanding their distribution patterns may be useful for clinical practice.

PMID- 24935850
TI  - [The influences of non-surgical periodontal treatment on gingival crevicular
      fluid levels of MMP-8 and tissue inhibitor of TIMP-1].
AB  - PURPOSE: To compare the levels of MMP-8 and TIMP-1 in the gingival crevicular
      fluid (GCF)of chronic periodontitis(CP) patients before and after non-surgical
      periodontal therapy. METHODS: Sulcus bleeding index (SBI), plaque index (PLI) and
      probing depth (PD) were detected before and after therapy. GCF was collected from
      CP patients before and after therapy. MMP-8 and TIMP-1 were determined by enzyme
      linked immunoabsorbent assay. The data was analyzed using paired-sample t test
      and multi-correlation analysis with SSPS 19.0 software package. RESULTS: The
      levels of MMP-8 and TIMP-1 decreased after therapy, and there was no significant
      difference in the MMP-8/TIMP-1 ratio. Correction analysis showed that a
      significant correction was found between MMP-8 and GCF weight. CONCLUSIONS: MMP-8
      and TIMP-1 decrease after non-surgical periodontal therapy.

PMID- 24935851
TI  - [Clinical analysis of caries status of the mandibular second molar].
AB  - PURPOSE: To collect the cases which have caries on the mandibular second molar
      and analyze the caries status and correlative factors. METHODS: Patients treated
      in the Department of Endodontics in West China Hospital of Stomatology were
      randomly collected. The baseline information, primary sites and severity of
      dental caries on the mandibular second molar, and eruption pattern of the
      mandibular third molar were recorded. The data was analyzed with SPSS13.0
      software package. RESULTS: Four hundred eighty-one patients including 227 males
      and 254 females were collected. Caries on the mandibular second molar starting
      from the occlusal, distal proximal and buccal surfaces accounted for 33.8%, 33.2%
      and 24.4%, respectively. Caries involving dental pulp (49.7%) were significantly
      more than deep and shallow to moderate caries (31.7% and 18.6%). Gender was not
      correlated with the site and severity of caries. However, impacted mandibular
      third molars and age were significantly related to both caries site and severity.
      CONCLUSIONS: Occlusal and distal proximal surfaces are the most predisposed sites
      to have caries on mandibular second molar. Impacted mandibular third molar and
      age are significantly related to caries of mandibular second molar.

PMID- 24935853
TI  - [Literature analysis of current bilingual teaching on stomatology in China].
AB  - PURPOSE: To investigate the current status and problems of bilingual teaching on
      stomatology in China. METHODS: Three database, including CNKI, Wanfang database
      and VIP were used to retrieve the articles of bilingual teaching on stomatology
      from January 2001 to December 2012. RESULTS: Fifty articles were included in this
      study and the following items, publishing time, foundation support, journals,
      authors and author affiliation, the course, teaching effects, research
      classification and main components of the articles were analyzed. The problems
      remained were also discussed. CONCLUSIONS: The level of current bilingual
      teaching on stomatology in China is low and great efforts are needed to make it
      better. Supported by Research Fund of Hebei United University(Z201333).

PMID- 24935852
TI  - [Fiber post versus metal screw post for repair of residual crowns and roots: a
      systematic review].
AB  - PURPOSE: To evaluate the restorative effectiveness of fiber post versus metal
      screw post through systematical review. METHODS: Randomized controlled trials
      (RCTs) data from the establishment of the database up to June 2013 were searched
      from MEDLINE (Ovid), PubMed, The Cochrane Library, Embase, Wanfang Data, VIP,
      CNKI and CBM using the designed strategy. After data extraction and quality
      review of the retrieved articles by two independent investigators, the softwares
      of RevMan 5.1.0 and GRAED profiler 3.2.2 were employed to process data analysis.
      RESULTS: Ten RCTs were finally included, of which 1 was English literature and 9
      were Chinese literatures. Meta analysis suggested that the survival rate of
      repair of adult and young permanent teeth was significantly higher using fiber
      post than metal screw post [RR=1.21,95%CI(1.13,1.30),
      P<0.01,RR=1.21,95%CI(1.10,1.34), P<0.01], and the results root fracture rate was
      significantly lower [RR=0.16,95%CI(0.05,0.48),P=0.001]. No significant difference
      was found in the rate of post-core fall off [RR=0.76,95%CI(0.33,1.73), P>0.05]
      and gingivitis [RR=0.71, 95%CI(0.27,1.88), P>0.05]. All outcomes were of low
      quality in the GRADE system. CONCLUSIONS: Compared with metal screw post, the
      survival rate is significantly higher and the root fracture rate is significantly
      lower by using fiber post. However, the conclusion is limited by lack of relevant
      studies, small sample sizes, inadequate quality and diversified methodology.
      Further study is needed by employing more well-designed, large-sample and multi
      center RCTs to verify the conclusion.

PMID- 24935854
TI  - [Research progress of nano-hydroxyapatite complexes in bone tissue regeneration].
AB  - As the nano-hydroxyapatite is the main inorganic component of bone tissue of the
      human body, artificial synthesis of nano-hydroxyapatite has attracted the most
      attention in the field of hard tissue repair. To make up multiple aspects of
      limitations for nano-hydroxyapatite material itself, nano-hydroxyapatite
      complexes have been widely evaluated and applied in bone repair. This paper
      reviewed the common nano-hydroxyapatite complexes and their research progress in
      bone regeneration. Supported by Research Fund of Science and Technology Committee
      of Shanghai Municipality (12NM0501600, 13NM1402102) and Medicine and Engineering
      Cross Project of Shanghai Jiao Tong University (YG2012MS29). 

PMID- 24935855
TI  - [Solitary median maxillary central incisor syndrome:a case of report].
AB  - Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly
      characterized by a symmetric central incisor of normal size, developed and
      erupted precisely in the midline of the maxilla in both primary and permanent
      dentitions. SMMCI may occur alone or be associated with other midline structures
      defects of the body or other systemic disorders. The best known association is
      holoprosencephaly (HPE). This paper reported a case of SMMCI that companied with
      other midline structures defects of the body. 

PMID- 24935856
TI  - Spinocerebellar ataxia type 10 in Peru: the missing link in the Amerindian origin
      of the disease.
AB  - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative
      disorder manifested by ataxia with a variable presentation of epileptic seizures,
      which is caused by a large expansion of an intronic ATTCT pentanucleotide repeat
      in ATXN10 on 22q13.3. Herein, we report the first description of SCA10 in a
      Peruvian family, supporting the Amerindian origin of SCA10 and the Panamerican
      geographical distribution of the disease in North, Central and South America.
      Moreover, the presence of an interruption motif in the SCA10 expansion along with
      epileptic seizures in this family supports the correlation between the two, as
      seen in other families. Finally, this is the first SCA10 patient ever observed
      outside of America, specifically in Italy. Since this patient is a Peruvian
      immigrant of Amerindian ancestry, our case report highlights the growing need for
      awareness amongst clinicians of seemingly geographically restricted rare
      diseases. 

PMID- 24935857
TI  - Karl Stern (1906-1975).
AB  - The forced migration process of German-speaking neurologists and psychiatrists
      under the Nazis during the 1930s and 40s is often preoccupied solely with
      "successful" concepts and therapeutic approaches. The case of German-Canadian
      neurologist Karl Stern (1906-1975) is very instructive, however, since the
      process of forced migration, for him, proved to be a transitionary process from
      his former cutting edge work in neuropathology and holist neurology in Germany to
      clinical psychiatry and the development of the new discipline of geriatric
      medicine in Canada.

PMID- 24935858
TI  - Outcome of limbic encephalitis with VGKC-complex antibodies: relation to
      antigenic specificity.
AB  - In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium
      channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins,
      leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein
      like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to
      the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)).
      Clinical, neuropsychology and MRI data were obtained from patient records for all
      LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by
      radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients
      were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs;
      and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment,
      the groups did not differ clinically or radiologically, but faciobrachial
      dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients
      received monthly intravenous methylprednisolone (MP) pulses. At the most recent
      follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure
      freedom rates did not differ between the Ab groups. Hippocampal atrophy had
      developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or
      LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory
      scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left
      with significantly poorer memory than the other two subgroups. Most VGKC-LE
      patients become seizure-free with pulsed monthly MP, but memory outcome is less
      favourable. Hippocampal atrophy and poor memory recovery is common in patients
      with LGI1-Abs and suggests permanent functional damage. More intense
      immunotherapies could improve outcomes in LGI1-Ab(+)-LE. 

PMID- 24935860
TI  - Modification of British Committee for Standards in Haematology diagnostic
      criteria for essential thrombocythaemia.

PMID- 24935859
TI  - Detection of copy number variations and their effects in Chinese bulls.
AB  - BACKGROUND: Copy number variations (CNVs) are a main source of genomic structural
      variations underlying animal evolution and production traits. Here, with one pure
      blooded Angus bull as reference, we describe a genome-wide analysis of CNVs based
      on comparative genomic hybridization arrays in 29 Chinese domesticated bulls and
      examined their effects on gene expression and cattle growth traits. RESULTS: We
      identified 486 copy number variable regions (CNVRs), covering 2.45% of the bovine
      genome, in 24 taurine (Bos taurus), together with 161 ones in 2 yaks (Bos
      grunniens) and 163 ones in 3 buffaloes (Bubalus bubalis). Totally, we discovered
      605 integrated CNVRs, with more "loss" events than both "gain" and "both" ones,
      and clearly clustered them into three cattle groups. Interestingly, we confirmed
      their uneven distributions across chromosomes, and the differences of
      mitochondrion DNA copy number (gain: taurine, loss: yak & buffalo). Furthermore,
      we confirmed approximately 41.8% (253/605) and 70.6% (427/605) CNVRs span cattle
      genes and quantitative trait loci (QTLs), respectively. Finally, we confirmed 6
      CNVRs in 9 chosen ones by using quantitative PCR, and further demonstrated that
      CNVR22 had significantly negative effects on expression of PLA2G2D gene, and both
      CNVR22 and CNVR310 were associated with body measurements in Chinese cattle,
      suggesting their key effects on gene expression and cattle traits. CONCLUSIONS:
      The results advanced our understanding of CNV as an important genomic structural
      variation in taurine, yak and buffalo. This study provides a highly valuable
      resource for Chinese cattle's evolution and breeding researches.

PMID- 24935862
TI  - "Bottle-opener" effect in bipolar hip prostheses dislocations.

PMID- 24935861
TI  - Simultaneous prevention of unintended pregnancy and STIs: a challenging
      compromise.
AB  - BACKGROUND: Unintended pregnancy and sexually transmitted infections (STIs) are
      the major negative consequences of unsafe sex. Both are common and have long-term
      social and health consequences. Barrier methods of contraception can prevent
      both, but unfortunately they are much less effective than the more modern methods
      at pregnancy prevention. Modern effective contraceptives, however, do not protect
      against STIs and some may increase the risk of acquisition of infection. This
      comprehensive review discusses the magnitude of burden of reproductive ill
      health, focussing on data from the European region, and explores the relationship
      between contraceptive use and STIs. METHODS: Searches were performed by using
      Medline, Popline, EMBASE, Cochrane Library and the Social Sciences Citation Index
      databases for relevant English language publications from 1995 to 2012. Summaries
      were discussed by the European Society of Human Reproduction and Embryology
      (ESHRE) Workshop Group. RESULTS: An understanding of patterns of sexual behaviour
      helps to understand the epidemiology of unintended pregnancy and STIs and gives
      pointers towards their prevention, but survey methodologies differ and results
      are hard to compare. Contraceptive prevalence and method mix vary widely between
      countries, and the use of the dual method of protection is very infrequent.
      Abortion rates have fallen in many European countries, particularly Eastern
      Europe, and contraceptive prevalence increased but unsafe abortion still accounts
      for 11% of maternal mortality in Eastern Europe. STIs are common but reporting
      systems are often rudimentary or non-existent and robust data are scarce.
      Providers still worry about the effect of intrauterine contraception on
      reproductive tract infections despite reassuring evidence to the contrary. New
      data on HIV acquisition and hormonal contraception are causing concern in
      settings where HIV infection is common. New developments in multipurpose
      technologies aimed at producing a single device/drug, which prevents infection
      and pregnancy simultaneously, are in early stages. While the benefits of national
      screening programmes for STIs remain uncertain, human papilloma virus (HPV)
      vaccination is clearly reducing HPV infection rates and gives hope for the public
      health benefits of other STI vaccines. CONCLUSIONS: The consequences of unsafe
      sex-unintended pregnancy and STI-continue to present major public health problems
      worldwide even in countries where the prevalence of use of modern contraception
      is high. Robust systems for routine data collection are sorely needed in most
      countries and systematic attempts to compare patterns of sexual behaviour across
      men and women of all ages would be welcome.

PMID- 24935863
TI  - The effect of temperature and menthol on carbonation bite.
AB  - Temperature and chemesthesis interact, but this interaction has not been fully
      examined for most irritants. The current experiments focus on oral pungency from
      carbonation. Previous work showed that cooling carbon dioxide (CO2) solutions to
      below tongue temperature enhanced rated bite. However, to the best of our
      knowledge, the effects of warming to above tongue temperature have not been
      examined. In Experiment 1, subjects sampled CO2 solutions at 4 nominal
      concentrations (0.0, 2.0, 2.8, and 4.0 v/v) * 5 temperatures (18.3, 24.5, 29.9,
      34.5, and 39.6 (o)C). Subjects dipped their tongue tips into samples and rated
      bite. As in previous work, subjects rated cool solutions (25.0 (o)C and lower) as
      more intense. Warming solutions above tongue temperature (39.6 (o)C) did not
      affect ratings. Experiment 2 examined warmer temperatures (18.3, 33.9, 39.0,
      44.9, and 48.2 oC). Bite was enhanced only at 48.2 oC, and a follow-up experiment
      suggested that enhancement was probably due to confusion between carbonation bite
      and mild heat pain. Experiment 3 examined the effect of menthol cooling by
      pretreating the tongue with menthol. Unlike physical cooling, menthol cooling had
      little or no effect on rated bite. The results are discussed in the context of
      candidate transduction mechanisms for carbonation sensation. 

PMID- 24935864
TI  - A combination of plant-derived odors reduces corticosterone and oxidative
      indicators of stress.
AB  - In this study, we measured typical stress markers in addition to oxidative status
      and reduced glutathione in erythrocytes, and plasma lipid peroxidation of
      restraint-stressed animals exposed to a combination of plant-derived odors (0.03%
      Z-3-hexen-1-ol, 0.03% E-2-hexenal, and 0.015% alpha-pinene in triethyl citrate).
      Male Wistar rats aged 6-7 weeks postnatal were exposed to vehicle (triethyl
      citrate, n = 12), plant-derived odors (n = 12), or 1% propionic acid odor (n =
      12) under control or stress conditions, and blood samples were collected.
      Restraint stress increased plasma glucose and plasma corticosterone
      concentrations by approximately 10% (P < 0.01) and 125% (P < 0.001),
      respectively, in vehicle-exposed animals. Similar increases were observed in
      animals exposed to a 1% propionic acid odor, indicating the novelty of odor
      exposure does not alter stress responsiveness. There was also an increase of
      approximately 15% in both erythrocytic oxidative status (P < 0.001) and plasma
      lipid peroxidation (P < 0.05), and a decrease of approximately the same magnitude
      in reduced glutathione (P < 0.05) in restrained animals with vehicle exposure.
      There were no differences observed between control and stress treatment with
      plant-derived odor exposure in any of the measured parameters. It was concluded
      that exposure to plant-derived odors reduce corticosterone, glucose, and redox
      responses elicited by psychological stress. 

PMID- 24935865
TI  - Efficient DNA fingerprinting based on the targeted sequencing of active
      retrotransposon insertion sites using a bench-top high-throughput sequencing
      platform.
AB  - In many crop species, DNA fingerprinting is required for the precise
      identification of cultivars to protect the rights of breeders. Many families of
      retrotransposons have multiple copies throughout the eukaryotic genome and their
      integrated copies are inherited genetically. Thus, their insertion polymorphisms
      among cultivars are useful for DNA fingerprinting. In this study, we conducted a
      DNA fingerprinting based on the insertion polymorphisms of active retrotransposon
      families (Rtsp-1 and LIb) in sweet potato. Using 38 cultivars, we identified
      2,024 insertion sites in the two families with an Illumina MiSeq sequencing
      platform. Of these insertion sites, 91.4% appeared to be polymorphic among the
      cultivars and 376 cultivar-specific insertion sites were identified, which were
      converted directly into cultivar-specific sequence-characterized amplified region
      (SCAR) markers. A phylogenetic tree was constructed using these insertion sites,
      which corresponded well with known pedigree information, thereby indicating their
      suitability for genetic diversity studies. Thus, the genome-wide comparative
      analysis of active retrotransposon insertion sites using the bench-top MiSeq
      sequencing platform is highly effective for DNA fingerprinting without any
      requirement for whole genome sequence information. This approach may facilitate
      the development of practical polymerase chain reaction-based cultivar diagnostic
      system and could also be applied to the determination of genetic relationships. 

PMID- 24935869
TI  - The Berry curvature of the Bogoliubov quasiparticle Bloch states in the
      unconventional superconductor Sr2RuO4.
AB  - We will extend the concept of electron band Berry curvatures to superconducting
      materials. We show that this can be defined for the Bogoliubov-de Gennes equation
      describing the superconducting state in a periodic crystal. In addition, the
      concept is exploited to understand the driving mechanism for the optical Kerr
      effect in time reversal symmetry breaking superconductors. Finally, we establish
      a sum rule analogue to the normal state Hall sum rule making quantitative contact
      between the imaginary part of the optical conductivity and the Berry curvature.
      The general theory will be applied and tested against the drosophila of the p
      wave paired materials Sr2RuO4. 

PMID- 24935870
TI  - The Importance of Terminal Values and Religious Experience of God's Presence and
      God's Absence in the Lives of University Students with Various Levels of Empathy.
AB  - The aims of the research I embarked on were: (a) to show the preference of
      terminal values in personal and in social character, as well to determine the
      level of religious experience--God's presence and God's absence, in groups of
      young people characterized by a high and low level of empathy and (b) to show the
      relation between terminal values in personal and in social character and
      religious experience: God's presence and God's absence, in groups of young people
      with a high and low level of empathy. In the research, the following methods were
      applied: The Scale of Religious Experience by Glaz-in order to define the level
      of religious experience: God's presence and God's absence, and Mehrabian and
      Epstein's Questionnaire Measure of Emotional Empathy-in order to define the level
      of empathy. In order to show the terminal values preference amongst young people,
      the Rokeach Value Survey was applied. The research was carried out in Krakow
      amongst 200 university students. The research has shown that students with a high
      level of empathy reveal a higher level of experience of God's presence than the
      people with a low level of it. University students with a high level of empathy
      amongst terminal values prefer most two values in personal character, that is
      wisdom and pleasure, and one in social character-family security. Similarly,
      students with a low level of empathy prefer most also two values in personal
      character, that is pleasure and freedom, and one in social character-family
      security. In the group of people with a high level of empathy, it is value in
      personal character-a sense of accomplishment-that contribute more to explaining
      the variance of religious experience of God's presence, and in group of people
      with a low level of empathy, it is social value-social recognition. Whereas in
      the group of people with a high level of empathy it is value in social character
      equality-that contribute more to explaining the variance of religious experience
      of God's absence, and in group of people with a low level of empathy, it is
      personal value-salvation.

PMID- 24935866
TI  - Comparative analysis of the primary transcriptome of Synechocystis sp. PCC 6803.
AB  - RNA-seq and especially differential RNA-seq-type transcriptomic analyses (dRNA
      seq) are powerful analytical tools, as they not only provide insights into gene
      expression changes but also provide detailed information about all promoters
      active at a given moment, effectively giving a deep insight into the
      transcriptional landscape. Synechocystis sp. PCC 6803 (Synechocystis 6803) is a
      unicellular model cyanobacterium that is widely used in research fields from
      ecology, photophysiology to systems biology, modelling and biotechnology. Here,
      we analysed the response of the Synechocystis 6803 primary transcriptome to
      different, environmentally relevant stimuli. We established genome-wide maps of
      the transcriptional start sites active under 10 different conditions relevant for
      photosynthetic growth and identified 4,091 transcriptional units, which provide
      information about operons, 5' and 3' untranslated regions (UTRs). Based on a
      unique expression factor, we describe regulons and relevant promoter sequences at
      single-nucleotide resolution. Finally, we report several sRNAs with an intriguing
      expression pattern and therefore likely function, specific for carbon depletion
      (CsiR1), nitrogen depletion (NsiR4), phosphate depletion (PsiR1), iron stress
      (IsaR1) or photosynthesis (PsrR1). This dataset is accompanied by comprehensive
      information providing extensive visualization and data access to allow an easy-to
      use approach for the design of experiments, the incorporation into modelling
      studies of the regulatory system and for comparative analyses. 

PMID- 24935871
TI  - Empathy and silence in pastoral care for traumatic grief and loss.
AB  - This paper evaluates silence as a therapeutic practice in pastoral care for
      traumatic grief and loss. Informed by the history of attachment and mourning
      theory, its research considers the basic effect that empathy has upon the
      therapeutic relationship around psychic difference. The study appraises the
      potential resources and detriments that empathic language may have for the grief
      process. Offering clinical examples in hospice chaplaincy, it refutes the idea
      that silence is formulaic tool to be used. It instead offers silence as the
      acceptance of the limits of empathic language and the affirmation of
      psychological difference and theological wholeness. 

PMID- 24935873
TI  - Do nurses have worse pregnancy outcomes than non-nurses?
AB  - BACKGROUND: Nurses encounter multiple occupational exposures at work which may
      harm their reproductive health. The purpose of the study was to compare pregnancy
      complications and outcomes including cesarean deliveries, tocolysis, miscarriage,
      and preterm labor between female nurses and comparable women who were not nurses
      in Taiwan. METHODS: This nationwide population-based study was performed using
      the National Health Insurance Research Database from 1997 to 2008. We identified
      3,656 pregnancies among 2,326 nurses and 111,889 pregnancies among 74,919 non
      nurses. A generalized estimating equation was used to compare risks between the
      two groups. RESULTS: The rates of tocolysis (28.6 vs 22.3%), miscarriage (6.0 vs
      5.3%), and preterm labor (8.1 vs 4.4%) were significantly higher among nurses
      than non-nurses. After adjustment for background differences, nurses had
      significantly higher risks for cesarean section (adjusted OR 1.12 [95% confidence
      interval (CI) 1.03-1.22]), tocolysis (OR 1.18 [95% CI 1.09-1.29]), and preterm
      labor (OR 1.46 [95% CI 1.28-1.67]) than non-nurses. CONCLUSIONS: Nurses are at
      higher risk for cesarean section, tocolysis, and preterm labor than non-nurses.
      Occupational exposure related to these adverse pregnancy outcomes should be
      examined. Strategies to decrease the risks should be developed to improve
      reproductive health among nurses.

PMID- 24935872
TI  - Adverse outcomes of frailty in the elderly: the Rotterdam Study.
AB  - To investigate the prevalence of frailty in a Dutch elderly population and to
      identify adverse health outcomes associated with the frailty phenotype
      independent of the comorbidities. Cross-sectional and longitudinal analyses
      within the Rotterdam Study (the Netherlands), a prospective population-based
      cohort study in persons aged >=55 years. Frailty was defined as meeting three or
      more of five established criteria for frailty, evaluating nutritional status,
      physical activity, mobility, grip strength and exhaustion. Intermediate frailty
      was defined as meeting one or two frailty criteria. Comorbidities were
      objectively measured. Health outcomes were assessed by means of questionnaires,
      physical examinations and continuous follow-up through general practitioners and
      municipal health authorities for mortality. Of 2,833 participants (median age
      74.0 years, inter quartile range 9) with sufficiently evaluated frailty criteria,
      163 (5.8 %) participants were frail and 1,454 (51.3 %) intermediate frail. Frail
      elderly were more likely to be older and female, to have an impaired quality of
      life and to have fallen or to have been hospitalized. 108 (72.0 %) frail
      participants had >=2 comorbidities, compared to 777 (54.4 %) intermediate frail
      and 522 (44.8 %) non-frail participants. Adjusted for age, sex and comorbidities,
      frail elderly had a significantly increased risk of dying within 3 years (HR 3.4;
      95 % CI 1.9-6.4), compared to the non-frail elderly. This study in a general
      Dutch population of community-dwelling elderly able to perform the frailty tests,
      demonstrates that frailty is common and that frail elderly are at increased risk
      of death independent of comorbidities.

PMID- 24935874
TI  - Antibodies to Delta/notch-like epidermal growth factor-related receptor in
      patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin
      lymphoma.
AB  - IMPORTANCE: The anti-Tr immune response is associated with paraneoplastic
      cerebellar degeneration and Hodgkin lymphoma (HL). One case series has reported
      that the Delta/notch-like epidermal growth factor-related receptor (DNER) is the
      actual target for anti-Tr antibodies, but this result has not been replicated.
      OBJECTIVE: To describe a patient with anti-Tr and confirm that DNER is the
      autoantigen for a series of patients with anti-Tr. DESIGN, SETTING, AND
      PARTICIPANTS: Observational study and analysis of biological samples for
      antibodies to DNER at the hospital of the University of Pennsylvania. We examined
      a cerebrospinal fluid sample from 1 patient with anti-Tr and serum and/or
      cerebrospinal fluid samples from 5 other patients with anti-Tr. EXPOSURE:
      Transfection of HEK293T and Hela cells to express DNER coupled to an enhanced
      green fluorescent protein tag using a plasmid previously used to detect human
      DNER antibodies. RESULTS: A man in his 30s with paraneoplastic cerebellar
      degeneration and anti-Tr underwent treatment with corticosteroids and intravenous
      immunoglobulin, resulting in clinical improvement before chemotherapy. Despite
      close oncologic follow-up, a biopsy, positron emission tomography, and computed
      tomography, he was not diagnosed as having HL until 6 months after symptom onset.
      The cerebrospinal fluid sample from this patient reacted with cells transfected
      to express DNER, as did cerebrospinal fluid and/or serum samples from 5 other
      patients with paraneoplastic cerebellar degeneration, HL, and anti-Tr. Only 4 of
      the 5 serum samples reacted to permeabilized cells enough to be distinguished
      from background, but all 5 serum samples convincingly labeled live cells, which
      had considerably less background. All 6 control serum samples and 1 serum sample
      from a patient previously diagnosed as having anti-Tr (but without HL or
      cerebellitis) did not recognize DNER. CONCLUSIONS AND RELEVANCE: This case
      demonstrates the importance of testing for the anti-Tr immune response in
      patients with cerebellar degeneration. The strong association of anti-Tr with HL
      requires careful surveillance for this tumor. We also confirm that DNER is the
      target antigen of the anti-Tr immune response. Screening for DNER antibodies
      against living transfected cells may offer an improved signal-to-noise
      characteristic compared with immunostaining of fixed, permeabilized cells.

PMID- 24935876
TI  - Adherence to surveillance guidelines after radical cystectomy: a population-based
      analysis.
AB  - OBJECTIVES: Surveillance after radical cystectomy is recommended to detect tumor
      recurrence and treatment complications. We evaluated adherence to National
      Comprehensive Cancer Network (NCCN) guidelines using a large population-based
      database. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results
      Medicare database was used to identify patients aged >=66 years diagnosed with
      nonmetastatic bladder cancer who had undergone radical cystectomy between 2000
      and 2007. Medicare claims information identified recommended surveillance tests
      for 2 years after cystectomy as outlined in the NCCN guidelines. Adherence was
      defined as receipt of urine cytology and imaging of the chest, abdomen, and
      pelvis in each year. We evaluated the effect of patient and provider
      characteristics on adherence, controlling for demographic and disease
      characteristics. RESULTS: Of 3,757 patients who had undergone radical cystectomy,
      2,990 (80%) were alive after 2 years. Adherence to all recommended investigations
      was 17% for the first and the second years following surgery. Among patients
      surviving 2 years, only 9% had complete surveillance in both years. In either
      year, adherence was less likely in patients with advanced pathologic stage
      (III/IV) (adjusted odds ratio [AOR] = 0.74, 95% CI: 0.60-0.91) and unmarried
      patients (AOR = 0.82, 95% CI: 0.68-0.99). Adherence was more likely in patients
      treated by high-volume surgeons (AOR = 2.00, 95% CI: 1.70-2.36) and those who saw
      a medical oncologist (AOR = 1.52, 95% CI: 1.27-1.82). We also observed
      significant geographic variability in adherence. CONCLUSION: Patterns of
      surveillance after radical cystectomy deviate considerably from NCCN
      recommendations. Despite increased utilization of radiographic imaging
      investigations, the omission of urine cytology significantly contributed to the
      low rate of overall adherence to surveillance guidelines. Uniform adherence to
      surveillance guidelines was observed in patients treated by high-volume surgeons.
      This suggests an important opportunity for quality improvement in bladder cancer
      care.

PMID- 24935877
TI  - Integrating research and practice: a new initiative from the Alliance for
      Continuing Education in the Health Professions.

PMID- 24935878
TI  - Trends in physician preferences for and use of sources of medical information in
      response to questions arising at the point of care: 2009-2013.
AB  - INTRODUCTION: Recent information on the preferences and trends of medical
      information sources for US practicing physicians in the past several years is
      lacking. The purpose of this study was to identify current format preferences and
      attitudes of physicians as well as trends over time to provide timely information
      for use in educational planning. METHODS: A survey instrument was developed and
      distributed in 2013 to US practicing physicians in several specialties. Data were
      aggregated and analyzed to understand trends across these physicians. Differences
      between and among demographic subsets of physicians, such as practice type and
      location, were observed by the use of inferential statistics. Additionally, using
      a similar survey fielded in 2009, these findings were analyzed to observe
      potential changes in the past 4 years. RESULTS: Peer-reviewed journal articles
      and continuing medical education (CME) are reported to be the most useful sources
      of medical information by physicians. Non-CME promotional meetings,
      pharmaceutical sales representatives, and managed care organizations are least
      useful or influential. Physicians are receiving more clinical questions from
      patient encounters in 2013 compared to 2009, and spend more time searching for
      information online. The use of many formats to receive medical information is
      increasing, including both technology-derived and traditional formats.
      DISCUSSION: Increases in clinical questions and time spent online indicate a
      heightened need for efficiencies in searching for medical information. New uses
      of technology in medical information delivery may allow educators an avenue to
      meet the rising needs of physicians.

PMID- 24935875
TI  - The determination of tRNALeu recognition nucleotides for Escherichia coli L/F
      transferase.
AB  - Escherichia coli leucyl/phenylalanyl-tRNA protein transferase catalyzes the tRNA
      dependent post-translational addition of amino acids onto the N-terminus of a
      protein polypeptide substrate. Based on biochemical and structural studies, the
      current tRNA recognition model by L/F transferase involves the identity of the 3'
      aminoacyl adenosine and the sequence-independent docking of the D-stem of an
      aminoacyl-tRNA to the positively charged cluster on L/F transferase. However,
      this model does not explain the isoacceptor preference observed 40 yr ago. Using
      in vitro-transcribed tRNA and quantitative MALDI-ToF MS enzyme activity assays,
      we have confirmed that, indeed, there is a strong preference for the most
      abundant leucyl-tRNA, tRNA(Leu) (anticodon 5'-CAG-3') isoacceptor for L/F
      transferase activity. We further investigate the molecular mechanism for this
      preference using hybrid tRNA constructs. We identified two independent sequence
      elements in the acceptor stem of tRNA(Leu) (CAG)-a G3:C70 base pair and a set of
      4 nt (C72, A4:U69, C68)-that are important for the optimal binding and catalysis
      by L/F transferase. This maps a more specific, sequence-dependent tRNA
      recognition model of L/F transferase than previously proposed.

PMID- 24935879
TI  - Autonomic arousal and learning in Web-based simulation: a feasibility study.
AB  - INTRODUCTION: Autonomic arousal is an important component of understanding
      learning as it is related to cognitive effort, attention, and emotional arousal.
      Currently, however, little is known about its relationship to online education.
      We conducted a study to determine the feasibility of measuring autonomic arousal
      and engagement in online continuing medical education (CME). METHOD: Using the
      Computer Simulation Assessment Tool (CSAT) platform, health care providers were
      randomly assigned to either high- or low-valence versions of a Web-based
      simulation on risk assessment for a returning veteran. Data were collected on
      participants' actions within the simulation, self-reported cognitive engagement,
      knowledge retention, and autonomic arousal measured using galvanic skin response
      (GSR). RESULTS: Participants in the high-valence condition (n = 7) chose a lower
      percentage of critical actions (M = 79.2, SD = 4.2) than participants in the low
      valence (n = 8) condition (M = 83.9, SD = 3.6, t(1,14) = 2.44, p = .03). While
      not statistically significant, high-valence participants reported higher
      cognitive engagement. Participants in the high-valence condition showed a larger
      increase in physiologic arousal when comparing mean tonic GSR during the
      orientation simulation to the study simulation (high-valence mean difference =
      4.21 MUS, SD = 1.23 vs low-valence mean difference = 1.64 MUS, SD = 2.32, t(1,13)
      = -2.62, p = .01). DISCUSSION: In addition to being consistent with previous
      engagement research, this experiment functioned as a feasibility study for
      measuring autonomic arousal in online CME. The current study provides a framework
      for future studies, which may use neurophysiology to identify the critical
      autonomic and engagement components associated with effective online learning.

PMID- 24935880
TI  - A comparison of matched and aggregated group outcomes data for evaluating
      continuing education of hematology and oncology health care professionals.
AB  - INTRODUCTION: Capturing educational outcomes from health care professionals is
      often challenging. Therefore, many providers utilize aggregated group data
      (comparing all preassessments to all postassessments) rather than matched group
      data (comparing pre- and postassessments only for those learners who completed
      both). To address the agreement between aggregate and matched outcomes, a
      preliminary analysis was conducted. METHODS: Matched and aggregated group data
      were compared from 4 hematology/oncology education series and 3 satellite
      symposia. Moore's Level 3 and 4 and outcomes were assessed using an electronic
      audience response system before and after each activity. Knowledge and competence
      shifts as well as the response spectrum for both groups were compared. RESULTS: A
      total of 2953 health care professionals were educated in 7 programs comprising
      128 live activities. The programs employed a combined total of 39 practice
      pattern, knowledge, competence, and self-assessed confidence/competence
      questions. All knowledge and competence shifts were within 10 absolute percentage
      points between the matched and aggregated groups with an average difference of
      3.4 percentage points. The 39 questions had 185 possible choices and 370 total
      possible responses. When all responses for the matched and aggregated groups were
      compared, 95% were within 5 absolute percentage points and 99% were within 10
      absolute percentage points. The agreement between the groups was found regardless
      of program or question type. DISCUSSION: Overall, the aggregated and matched
      group results were comparable. Aggregated data may be sufficiently accurate for
      many program evaluation purposes, depending on the degree of certainty required
      by the evaluation stakeholders.

PMID- 24935882
TI  - Promoting and supporting research in continuing education in the health
      professions: ACEhp's commitment to advancing professional practice.

PMID- 24935883
TI  - Estimating health care cost savings from an educational intervention to prevent
      bleeding-related complications: the outcomes impact analysis model.
AB  - INTRODUCTION: Investments in continuing medical education (CME) exceed $2 billion
      annually, but few studies report the economic impact of CME activities. Analysis
      of patient-level economic outcomes data is often not feasible. Accordingly, we
      developed a model to illustrate estimation of the potential economic impact
      associated with CME activity outcomes. METHODS: Outcomes impact analysis
      demonstrated how costs averted from a CME symposium that promoted prevention of
      bleeding-related complications (BRC) and reoperation for bleeding (RFB) in
      cardiac and thoracic operations could be estimated. Model parameter estimates
      were from published studies of costs associated with BRC and RFB. Operative
      volume estimates came from the Society of Thoracic Surgeons workforce data. The
      base case predicted 3 in 10 participants preventing one BRC or RFB in 2% or 1.5%
      of annual operations, respectively. Probabilistic sensitivity analysis (PSA)
      evaluated the effect of parameter uncertainty. RESULTS: 92% of participants (n =
      133) self-reported commitment to change, a validated measure of behavior change.
      For BRC, estimates for costs averted were $1,502,769 (95% confidence interval
      [CI], $869,860-$2,359,068) for cardiac operations and $2,715,246 (95% CI,
      $1,590,308-$4,217,092) for thoracic operations. For RFB, the savings estimates
      were $2,233,988 (95% CI, $1,223,901-$3,648,719). DISCUSSION: Our economic model
      demonstrates that application of CME-related learning to prevent bleeding
      complications may yield substantial cost savings. Model prediction of averted
      costs associated with CME allows estimation of the economic impact on outcomes in
      the absence of patient-level outcomes data related to CME activities.

PMID- 24935884
TI  - Relationship among practice change, motivation, and self-efficacy.
AB  - INTRODUCTION: The relationship between an individual's sense of self-efficacy,
      motivation to change, and the implementation of improvement programs has been
      reported. This research reports the relationship among self-efficacy, motivation
      to change, and intent to implement continuing medical education (CME) activity
      learnings. METHODS: The measure of individual sense of self-efficacy was a 4-item
      scale. The measure of motivation was a 4-item scale following on the work of
      Johnson, et al. The self-efficacy scale has been confirmed for structure, and
      together the 2 scales provide indicators of 3 underlying variables-2 self
      efficacy constructs and a motivation variable. In addition, a global intent to
      implement measure was collected. RESULTS: Preliminary analysis demonstrates a
      significant relationship between a self-efficacy construct, the motivation to
      change construct, and global intent to change. Specifically, the sense of
      efficacy in effecting change in the practice environment is predictive of a high
      level of motivation to change, which, in turn, is predictive of formation of an
      intent to change practice patterns. DISCUSSION: Further inspection of the
      motivation to change construct suggests that it mediates the self-efficacy
      constructs' effect on intent. This is consistent with an earlier report on the
      relationship among self-efficacy, barriers to change, and stated intent. This new
      finding suggests that the proximal construct motivation completely masks an
      important underlying causal relationship that appears to contribute to practice
      change following CME: self-efficacy. A focus on the participants' sense of self
      agency may provide a path to practice change.

PMID- 24935885
TI  - High Reading Skills Mask Dyslexia in Gifted Children.
AB  - This study investigated how gifted children with dyslexia might be able to mask
      literacy problems and the role of possible compensatory mechanisms. The sample
      consisted of 121 Dutch primary school children that were divided over four groups
      (typically developing [TD] children, children with dyslexia, gifted children,
      gifted children with dyslexia). The test battery included measures of literacy
      (reading/spelling) and cognitive abilities related to literacy and language
      (phonological awareness [PA], rapid automatized naming [RAN], verbal short-term
      memory [VSTM], working memory [WM], grammar, and vocabulary). It was hypothesized
      that gifted children with dyslexia would outperform children with dyslexia on
      literacy tests. In addition, a core-deficit model including dyslexia-related
      weaknesses and a compensational model involving giftedness-related strengths were
      tested using Bayesian statistics to explain their reading/spelling performance.
      Gifted children with dyslexia performed on all literacy tests in between children
      with dyslexia and TD children. Their cognitive profile showed signs of weaknesses
      in PA and RAN and strengths in VSTM, WM, and language skills. Findings indicate
      that phonology is a risk factor for gifted children with dyslexia, but this is
      moderated by other skills such as WM, grammar, and vocabulary, providing
      opportunities for compensation of a cognitive deficit and masking of literacy
      difficulties. 

PMID- 24935886
TI  - The Contributions of Phonological and Morphological Awareness to Literacy Skills
      in the Adult Basic Education Population.
AB  - The Adult Basic Education (ABE) population consists of a wide range of abilities
      with needs that may be unique to this set of learners. The purpose of this study
      was to better understand the relative contributions of phonological decoding and
      morphological awareness to spelling, vocabulary, and comprehension across a
      sample of ABE students. In this study, phonological decoding was a unique
      predictor of spelling ability, listening comprehension, and reading
      comprehension. We also found that morphological awareness was a unique predictor
      of spelling ability, vocabulary, and listening comprehension. Morphological
      awareness indirectly contributed to reading comprehension through vocabulary.
      These findings suggest the need for morphological interventions for this group of
      learners. 

PMID- 24935887
TI  - Using Spelling to Screen Bilingual Kindergarteners At Risk for Reading
      Difficulties.
AB  - For bilingual children, the results of language and literacy screening tools are
      often hard to interpret. This leads to late referral for specialized assessment
      or inappropriate interventions. To facilitate the early identification of reading
      difficulties in English, we developed a method of screening that is theory-driven
      yet suitable for first-language (L1) and second-language learners of English. We
      administered five conventional tests (phonological awareness, vocabulary,Wide
      Range Achievement Test-4[WRAT-4] spelling, letter identification, rapid naming of
      digits) to 127 five-year-olds (60 English-L1, 67 Mandarin-L1) about 6 months
      after they started kindergarten, and used the WRAT-4 word reading score 6 months
      later as the outcome measure. Consistent with previous research, and with
      children with reading disabilities defined as below the 25 percentile on the
      reading outcome, logistic regression revealed that the full set of screening
      measures predicted reading disability status. However, when each predictor was
      taken as a single measure, spelling scores provided the best fit in terms of the
      compromise between sensitivity (.75) and specificity (.73) for an optimal cutoff
      point. Based on this exploratory study, group-administered spelling tasks could
      provide an efficient solution to screening difficulties in large classes of
      bilingual children. 

PMID- 24935888
TI  - Mortality of registered drug users in Central Asia.
AB  - BACKGROUND: Within the fifth phase of the Central Asia Drug Action Programme
      (CADAP) covering five post-Soviet Central Asian countries, an analysis of the
      mortality of drug users was performed. The results for Kazakhstan and Uzbekistan
      are presented in detail in this paper since results from Kyrgyzstan and
      Tajikistan are not considered valid and Turkmenistan did not provide data at all.
      METHODS: A system of registration of all users of illegal drugs known to the
      health and/or law enforcement authorities ("narcological registers") exists in
      Central Asian countries inherited from the system of Soviet "narcology".
      According to the legal norms, the death of a registered person should be
      recorded. We conducted indirect standardisation of crude mortality rates and
      computed the standardised mortality ratio (SMR) comparing observed number of
      deaths with expected number of deaths according to age and gender specific
      mortality rates in the general population of the same country. RESULTS: The
      results show excess mortality in registered drug users, particularly in
      registered females, in Uzbekistan (the latest available SMR for all those
      registered is 7.4; the SMR in females is 16.3) and Kazakhstan (4.0 and 12.9). The
      excess mortality is highest among young adults (18-34) in all the studies.
      CONCLUSION: Taking into account the limited quality and reliability of the data -
      first of all, the likely under-reporting of deaths in the narcological registers 
      the crude mortality rate among registered drug users is quite high when compared
      to EU countries. The SMR in total is comparably lower as a result of the high
      background mortality in the general population. This excess mortality is
      preventable and should be targeted by the national drug policies. Specifically,
      the programmes should target registered and unregistered female drug users.

PMID- 24935889
TI  - Comparison of chronic type A aortic dissection with acute type A dissection of
      short-term and long-term survival rate.

PMID- 24935890
TI  - Morphometric analysis of variation in the sternum with sex and age.
AB  - Age and sex-related variations in sternum morphology may affect the thoracic
      injury tolerance. Male and female sternum size and shape variation was
      characterized for ages 0-100 from landmarks collected from 330 computed
      tomography scans. Homologous landmarks were analyzed using Procrustes
      superimposition to produce age and sex-specific functions of 3D-sternum
      morphology representing the combined size and shape variation and the isolated
      shape variation. Significant changes in the combined size and shape variation and
      isolated shape variation of the sternum were found to occur with age in both
      sexes. Sternal size increased from birth through age 30 and retained a similar
      size for ages 30-100. The manubrium expanded laterally from birth through age 30,
      becoming wider in relation to the sternal body. In infancy, the manubrium was 1.1
      1.2 times the width of the sternal body and this width ratio increased to 1.6-1.8
      for adults. The manubrium transformed from a circular shape in infancy to an oval
      shape in early childhood. The distal sternal body became wider in relation to the
      proximal sternal body from birth through age 30 and retained this characteristic
      throughout adulthood. The most dramatic changes in sternum morphology occur in
      childhood and young adulthood when the sternum is undergoing ossification. The
      lesser degree of ossification in the pediatric sternum may be partly responsible
      for the prevalence of thoracic organ injuries as opposed to thoracic skeletal
      injuries in pediatrics. Sternum fractures make up a larger portion of thoracic
      injury patterns in adults with fully ossified sternums. The lack of substantial
      size or shape changes in the sternum from age 30-100 suggests that the increased
      incidence of sternal fracture seen in the elderly may be due to cortical
      thickness or bone mineral density changes in the sternum as opposed to
      morphological changes.

PMID- 24935891
TI  - Electronic nicotine delivery systems (ENDS): new evidence from the State and
      Community Tobacco Control Research Initiative.

PMID- 24935892
TI  - The availability of electronic cigarettes in U.S. retail outlets, 2012: results
      of two national studies.
AB  - BACKGROUND: Since their introduction in 2007, electronic cigarette ('e
      cigarette') awareness and use has grown rapidly. Little is known about variation
      in e-cigarette availability across areas with different levels of tobacco taxes
      and smoke-free air policies. This paper looks at US retail availability of e
      cigarettes and factors at the store, neighbourhood and policy levels associated
      with it. METHODS: In-person store audit data collected in 2012 came from two
      national samples of tobacco retailers in the contiguous US. Study 1 collected
      data from a nationally representative sample of tobacco retailers (n=2165). Study
      2 collected data from tobacco retailers located in school enrolment zones for
      nationally representative samples of 8th, 10th and 12th grade public school
      students (n=2526). RESULTS: In 2012, e-cigarette retail availability was 34% in
      study 1 and 31% in study 2. Tobacco, pharmacy and gas/convenience stores were
      more likely to sell e-cigarettes than beer/wine/liquor stores. Retail
      availability of e-cigarettes was more likely in neighbourhoods with higher median
      household income (study 1), and lower percent of African-American (studies 1 and
      2) and Hispanic residents (study 2). Price of traditional cigarettes was
      inversely related to e-cigarette availability. Stores in states with an American
      Lung Association Smoke-Free Air grade of F (study 1) or D (study 2) compared with
      A had increased likelihood of having e-cigarettes. CONCLUSIONS: Currently, e
      cigarette availability appears more likely in areas with weak tax and smoke-free
      air policies. Given the substantial availability of e-cigarettes at tobacco
      retailers nationwide, states and localities should monitor the sales and
      marketing of e-cigarettes at point of sale (POS).

PMID- 24935893
TI  - Wanna know about vaping? Patterns of message exposure, seeking and sharing
      information about e-cigarettes across media platforms.
AB  - BACKGROUND: Awareness and use of electronic cigarettes has rapidly grown in the
      USA recently, in step with increased product marketing. Using responses to a
      population survey of US adults, we analysed demographic patterns of exposure to,
      searching for and sharing of e-cigarette-related information across media
      platforms. METHODS: An online survey of 17,522 US adults was conducted in 2013.
      The nationally representative sample was drawn from GfK Group's KnowledgePanel
      plus off-panel recruitment. Fixed effects logit models were applied to analyse
      relationships between exposure to, searching for and sharing of e-cigarette
      related information and demographic characteristics, e-cigarette and tobacco use,
      and media behaviours. RESULTS: High levels of awareness about e-cigarettes were
      indicated (86% aware; 47% heard through media channels). Exposure to e-cigarette
      related information was associated with tobacco use, age, gender, more education,
      social media use and time spent online. Although relatively small proportions of
      the sample had searched for (~5%) or shared (~2%) e-cigarette information, our
      analyses indicated demographic patterns to those behaviours. Gender, high income
      and using social media were associated with searching for e-cigarette
      information; lesbian, gay and bisexual and less education were associated with
      sharing. Current tobacco use, age, being Hispanic and time spent online were
      associated with both searching and sharing. CONCLUSIONS: US adults are widely
      exposed to e-cigarette marketing through the media; such marketing may
      differentially target specific demographic groups. Further research should
      longitudinally examine how exposure to, searching for and sharing of e-cigarette
      information relate to subsequent use of e-cigarettes and/or combustible tobacco.

PMID- 24935894
TI  - A cross-sectional examination of marketing of electronic cigarettes on Twitter.
AB  - BACKGROUND: Rapid increases in marketing of e-cigarettes coincide with growth in
      e-cigarette use in recent years; however, little is known about how e-cigarettes
      are marketed on social media platforms. METHODS: Keywords were used to collect
      tweets related to e-cigarettes from the Twitter Firehose between 1 May 2012 and
      30 June 2012. Tweets were coded for smoking cessation mentions, as well as health
      and safety mentions, and were classified as commercial or non-commercial
      ('organic') tweets using a combination of Naive Bayes machine learning methods,
      keyword algorithms and human coding. Metadata associated with each tweet were
      used to examine the characteristics of accounts tweeting about e-cigarettes.
      RESULTS: 73,672 tweets related to e-cigarettes were captured in the study period,
      90% of which were classified as commercial tweets. Accounts tweeting commercial e
      cigarette content were associated with lower Klout scores, a measure of
      influence. Commercial tweeting was largely driven by a small group of highly
      active accounts, and 94% of commercial tweets included links to websites, many of
      which sell or promote e-cigarettes. Approximately 10% of commercial and organic
      tweets mentioned smoking cessation, and 34% of commercial tweets included
      mentions of prices or discounts for e-cigarettes. CONCLUSIONS: Twitter appears to
      be an important marketing platform for e-cigarettes. Tweets related to e
      cigarettes were overwhelmingly commercial, and a substantial proportion mentioned
      smoking cessation. E-cigarette marketing on Twitter may have public health
      implications. Continued surveillance of e-cigarette marketing on social media
      platforms is needed.

PMID- 24935895
TI  - Four hundred and sixty brands of e-cigarettes and counting: implications for
      product regulation.
AB  - INTRODUCTION: E-cigarettes are largely unregulated and internet sales are
      substantial. This study examines how the online market for e-cigarettes has
      changed over time: in product design and in marketing messages appearing on
      websites. METHODS: Comprehensive internet searches of English-language websites
      from May-August 2012 and December 2013-January 2014 identified brands, models,
      flavours, nicotine strengths, ingredients and product claims. Brands were divided
      into older and newer groups (by the two searches) for comparison. RESULTS: By
      January 2014 there were 466 brands (each with its own website) and 7764 unique
      flavours. In the 17 months between the searches, there was a net increase of 10.5
      brands and 242 new flavours per month. Older brands were more likely than newer
      brands to offer cigalikes (86.9% vs. 52.1%, p<0.01), and newer brands more likely
      to offer the more versatile eGos and mods (75.3% vs. 57.8%, p<0.01). Older brands
      were significantly more likely to claim that they were healthier and cheaper than
      cigarettes, were good substitutes where smoking was banned and were effective
      smoking cessation aids. Newer brands offered more flavours per brand (49 vs. 32,
      p<0.01) and were less likely to compare themselves with conventional cigarettes.
      CONCLUSIONS: The number of e-cigarette brands is large and has been increasing.
      Older brands tend to highlight their advantages over conventional cigarettes
      while newer brands emphasise consumer choice in multiple flavours and product
      versatility. These results can serve as a benchmark for future research on the
      impact of upcoming regulations on product design and advertising messages of e
      cigarettes.

PMID- 24935896
TI  - Effects of advertisements on smokers' interest in trying e-cigarettes: the roles
      of product comparison and visual cues.
AB  - INTRODUCTION: Electronic cigarettes (e-cigarettes) are battery-powered nicotine
      delivery devices that have become popular among smokers. We conducted an
      experiment to understand adult smokers' responses to e-cigarette advertisements
      and investigate the impact of ads' arguments and imagery. METHODS: A U.S.
      national sample of smokers who had never tried e-cigarettes (n=3253) participated
      in a between-subjects experiment. Smokers viewed an online advertisement
      promoting e-cigarettes using one of three comparison types (emphasising
      similarity to regular cigarettes, differences or neither) with one of three
      images, for nine conditions total. Smokers then indicated their interest in
      trying e-cigarettes. RESULTS: Ads that emphasised differences between e
      cigarettes and regular cigarettes elicited more interest than ads without
      comparisons (p<0.01), primarily due to claims about e-cigarettes' lower cost,
      greater healthfulness and utility for smoking cessation. However, ads that
      emphasised the similarities of the products did not differ from ads without
      comparisons. Ads showing a person using an e-cigarette created more interest than
      ads showing a person without an e-cigarette (p<0.01). CONCLUSIONS: Interest in
      trying e-cigarettes was highest after viewing ads with messages about differences
      between regular and electronic cigarettes and ads showing product use. If e
      cigarettes prove to be harmful or ineffective cessation devices, regulators might
      restrict images of e-cigarette use in advertising, and public health messages
      should not emphasise differences between regular and electronic cigarettes. To
      inform additional regulations, future research should seek to identify what
      advertising messages and features appeal to youth.

PMID- 24935897
TI  - A baseline understanding of state laws governing e-cigarettes.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) have been available for purchase
      in the USA since 2007, and have grown rapidly in popularity. Currently, there are
      no federal restrictions on e-cigarettes; therefore, any regulations are under the
      purview of state and/or local governments. This study examines state laws
      governing e-cigarettes through youth access restrictions, smoke-free air
      requirements and/or excise taxation. METHODS: Codified statutory and
      administrative laws, attorney general opinions, executive orders, and revenue
      notices and rulings effective as of 15 November 2013 for all 50 states and the
      District of Columbia, were compiled using Boolean searches in Lexis-Nexis and
      Westlaw. All laws were analysed by two study authors to determine the presence
      and components of relevant provisions. Two categories of laws were identified;
      (1) explicit e-cigarette laws and (2) laws focused on tobacco-derived and/or
      nicotine-containing products. RESULTS: Thirty-four states' laws address e
      cigarettes either explicitly or as part of language applying to tobacco-derived
      or nicotine-containing products. Laws explicitly addressing e-cigarettes
      primarily focus on youth access (22 states) or smoke-free air (12 states); only
      Minnesota imposes an excise tax on e-cigarettes. Similarly, tobacco-derived or
      nicotine-containing products are primarily regulated through youth access
      restrictions (6 states), smoke-free air laws (5 states), or excise taxation (2
      states). CONCLUSIONS: In the current absence of federal law governing e
      cigarettes, more than one-half of the states have taken the initiative to
      regulate these products. The opportunity exists for the remaining states to
      incorporate e-cigarette-related restrictions into their pre-existing tobacco
      control laws.

PMID- 24935899
TI  - Research support for effective state and community tobacco control programme
      response to electronic nicotine delivery systems.
AB  - OBJECTIVE: To identify unmet research needs of state and community tobacco
      control practitioners pertaining to electronic nicotine delivery systems (ENDS or
      e-cigarettes) that would inform policy and practice efforts at the state and
      community levels, and to describe ENDS-related research and dissemination
      activities of the National Cancer Institute-funded State and Community Tobacco
      Control Research Initiative. METHODS: To determine specific research gaps
      relevant to state and community tobacco control practice, we analysed survey data
      collected from tobacco control programmes (TCPs) in all 50 U.S. states and the
      District of Columbia (N=51). Survey items covered a range of ENDS issues: direct
      harm to users, harm of secondhand vapour, cessation, flavours, constituents and
      youth access. RESULTS: There is no ENDS topic on which a majority of state TCP
      managers feel very informed. They feel least informed about harms of secondhand
      vapour while also reporting that this information is among the most important for
      their programme. A majority (N=31) of respondents indicated needs for research on
      the implications of ENDS products for existing policies. CONCLUSIONS: TCP
      managers report that ENDS research is highly important for practice and need
      research-based information to inform decision making around the inclusion of ENDS
      in existing tobacco control policies. For optimal relevance to state and
      community TCPs, research on ENDS should prioritise study of the health effects of
      ENDS use and secondhand exposure to ENDS vapour in the context of existing
      tobacco control policies.

PMID- 24935898
TI  - The impact of price and tobacco control policies on the demand for electronic
      nicotine delivery systems.
AB  - BACKGROUND: While much is known about the demand for conventional cigarettes,
      little is known about the determinants of demand for electronic nicotine delivery
      systems (ENDS or e-cigarettes). The goal of this study is to estimate the own and
      cross-price elasticity of demand for e-cigarettes and to examine the impact of
      cigarette prices and smoke-free policies on e-cigarette sales. METHODS: Quarterly
      e-cigarette prices and sales and conventional cigarette prices from 2009 to 2012
      were constructed from commercial retail store scanner data from 52 U.S. markets,
      for food, drug and mass stores, and from 25 markets, for convenience stores.
      Fixed-effects models were used to estimate the own and cross-price elasticity of
      demand for e-cigarettes and associations between e-cigarette sales and cigarette
      prices and smoke-free policies. RESULTS: Estimated own price elasticities for
      disposable e-cigarettes centred around -1.2, while those for reusable e
      cigarettes were approximately -1.9. Disposable e-cigarette sales were higher in
      markets where reusable e-cigarette prices were higher and where less of the
      population was covered by a comprehensive smoke-free policy. There were no
      consistent and statistically significant relationships between cigarette prices
      and e-cigarette sales. CONCLUSIONS: E-cigarette sales are very responsive to own
      price changes. Disposable e-cigarettes appear to be substitutes for reusable e
      cigarettes. Policies increasing e-cigarette retail prices, such as limiting
      rebates, discounts and coupons and imposing a tax on e-cigarettes, could
      potentially lead to significant reductions in e-cigarette sales. Differential tax
      policies based on product type could lead to substitution between different types
      of e-cigarettes.

PMID- 24935900
TI  - History of childhood maltreatment in intermittent explosive disorder and suicidal
      behavior.
AB  - Intermittent Explosive Disorder (IED) is a relatively common disorder of
      impulsive aggression that typically emerges by adulthood. Maltreatment in
      childhood (CM) may contribute to the development of IED, but little is known
      about the association between CM and IED, including about how subtypes of CM may
      specifically relate to IED. This study aimed to test the association between CM
      and IED diagnosis. A second aim was to examine history of CM in suicide
      attempters, and to explore whether impulsivity and aggression account for the
      relationship between CM and suicide attempt (SA). Adults with Intermittent
      Explosive Disorder (IED; n = 264), with non-IED psychiatric (Axis I or II)
      disorders (psychiatric controls; PC; n = 199), and with no psychiatric disorder
      (healthy control subjects; HC; n = 185) were assessed for history of childhood
      maltreatment, aggression, impulsivity, and history of SA. IED subjects reported
      significantly greater CM compared to PC and HC subjects, and suicide attempters
      (n = 62) reported greater CM compared to non-attempters (n = 586). Physical abuse
      in childhood was independently associated with IED, while sexual abuse and
      emotional abuse were independently associated with SA. Impulsivity and aggression
      were potential mediators of the relationship between physical abuse and IED and
      emotional abuse and SA, but sexual abuse was associated with SA independently of
      aggression and impulsivity. The results suggest pathways by which environmental
      factors may influence impulsivity and aggression and, in turn, clinically
      significant self- and other-directed aggression. 

PMID- 24935901
TI  - Evaluation of neurotransmitter receptor gene expression identifies GABA receptor
      changes: a follow-up study in antipsychotic-naive patients with first-episode
      psychosis.
AB  - A study of the gene expression levels in the blood of individuals with
      schizophrenia in the beginning of the disease, such as first-episode psychosis
      (FEP), is useful to detect gene expression changes in this disorder in response
      to treatment. Although a large number of genetic studies on schizophrenia have
      been conducted, little is known about the effects of antipsychotic treatment on
      gene expression. The aim of the present study was to examine differences in the
      gene expression in the blood of antipsychotic-naive FEP patients before and after
      risperidone treatment (N = 44) and also to verify the correlation with treatment
      response. In addition, we determined the correlations between differentially
      expressed genes and clinical variables. The expression of 40 neurotransmitter and
      neurodevelopment-associated genes was assessed using the RT2 Profiler PCR Array.
      The results indicated that the GABRR2 gene was downregulated after risperidone
      treatment, but no genes were associated with response to treatment and clinical
      variables after Bonferroni correction. GABRR2 downregulation after treatment can
      both suggest an effect of risperidone treatment or processes related to disease
      progression, either not necessarily associated with the improvement of symptoms.
      Despite this change was observed in blood, this decrease in GABRR2 mRNA levels
      might be an effect of changes in GABA concentrations or other systems interplay
      consequently to D2 blockage induced by risperidone, for example. Thus, it is
      important to consider that antipsychotics or the progression of psychotic
      disorders might interfere with gene expression.

PMID- 24935903
TI  - Reconciling embodied and distributional accounts of meaning in language.
AB  - Over the past 15 years, there have been two increasingly popular approaches to
      the study of meaning in cognitive science. One, based on theories of embodied
      cognition, treats meaning as a simulation of perceptual and motor states. An
      alternative approach treats meaning as a consequence of the statistical
      distribution of words across spoken and written language. On the surface, these
      appear to be opposing scientific paradigms. In this review, we aim to show how
      recent cross-disciplinary developments have done much to reconcile these two
      approaches. The foundation to these developments has been the recognition that
      intralinguistic distributional and sensory-motor data are interdependent. We
      describe recent work in philosophy, psychology, cognitive neuroscience, and
      computational modeling that are all based on or consistent with this conclusion.
      We conclude by considering some possible directions for future research that
      arise as a consequence of these developments.

PMID- 24935904
TI  - Motion artifact reduction in pediatric diffusion tensor imaging using fast
      prospective correction.
AB  - PURPOSE: To evaluate the patterns of head motion in scans of young children and
      to examine the influence of corrective techniques, both qualitatively and
      quantitatively. We investigate changes that both retrospective (with and without
      diffusion table reorientation) and prospective (implemented with a short
      navigator sequence) motion correction induce in the resulting diffusion tensor
      measures. MATERIALS AND METHODS: Eighteen pediatric subjects (aged 5-6 years)
      were scanned using 1) a twice-refocused, 2D diffusion pulse sequence, 2) a
      prospectively motion-corrected, navigated diffusion sequence with reacquisition
      of a maximum of five corrupted diffusion volumes, and 3) a T1 -weighted
      structural image. Mean fractional anisotropy (FA) values in white and gray matter
      regions, as well as tractography in the brainstem and projection fibers, were
      evaluated to assess differences arising from retrospective (via FLIRT in FSL) and
      prospective motion correction. In addition to human scans, a stationary phantom
      was also used for further evaluation. RESULTS: In several white and gray matter
      regions retrospective correction led to significantly (P < 0.05) reduced FA means
      and altered distributions compared to the navigated sequence. Spurious
      tractographic changes in the retrospectively corrected data were also observed in
      subject data, as well as in phantom and simulated data. CONCLUSION: Due to the
      heterogeneity of brain structures and the comparatively low resolution (~2 mm) of
      diffusion data using 2D single shot sequencing, retrospective motion correction
      is susceptible to distortion from partial voluming. These changes often
      negatively bias diffusion tensor imaging parameters. Prospective motion
      correction was shown to produce smaller changes.

PMID- 24935905
TI  - Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by
      cladosporin.
AB  - Malaria parasites inevitably develop drug resistance to anti-malarials over time.
      Hence the immediacy for discovering new chemical scaffolds to include in
      combination malaria drug therapy. The desirable attributes of new
      chemotherapeutic agents currently include activity against both liver and blood
      stage malaria parasites. One such recently discovered compound called cladosporin
      abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA
      synthetase (PfKRS), an enzyme central to protein translation. Here, we present
      crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that
      reveals cladosporin's remarkable ability to mimic the natural substrate adenosine
      and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin
      sandwiches between critical adenine-recognizing residues while its pyran ring
      fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights
      ample space within PfKRS active site for further chemical derivatization of
      cladosporin. Such derivatives may be useful against additional human pathogens
      that retain high conservation in cladosporin chelating residues within their
      lysyl-tRNA synthetase. 

PMID- 24935906
TI  - Diffusion-weighted imaging and magnetic resonance proton spectroscopy following
      preterm birth.
AB  - AIM: To study the associations between magnetic resonance proton spectroscopy
      (MRS) data and apparent diffusion coefficients (ADC) from the preterm brain with
      developmental outcome at 18 months corrected age and clinical variables.
      MATERIALS AND METHODS: A prospective observational cohort study of 67 infants
      born before 35 weeks gestational age who received both magnetic resonance imaging
      of the brain between 37 and 44 weeks corrected gestational age and developmental
      assessment around 18 months corrected age. RESULTS: No relationships were found
      between ADC values and MRS results or outcome. MRS ratios involving N-acetyl
      aspartate (NAA) from the posterior white matter were associated with "severe" and
      "moderate to severe" difficulties, and fine motor scores were significantly lower
      in participants with a visible lactate doublet in the posterior white matter. The
      presence of a patent ductus arteriosus (PDA) was the only clinical factor related
      to NAA ratios. CONCLUSION: Altered NAA levels in the posterior white matter may
      reflect subtle white matter injury associated with neuro-developmental
      difficulties, which may be related to a PDA. Further work is needed to assess the
      longer-term neuro-developmental implications of these findings, and to study the
      effect of PDAs on developmental outcome in later childhood/adolescence.

PMID- 24935902
TI  - Environmental controls on fungal community composition and abundance over 3 years
      in native and degraded shrublands.
AB  - Soil fungal communities have high local diversity and turnover, but the relative
      contribution of environmental and regional drivers to those patterns remains
      poorly understood. Local factors that contribute to fungal diversity include soil
      properties and the plant community, but there is also evidence for regional
      dispersal limitation in some fungal communities. We used different plant
      communities with different soil conditions and experimental manipulations of both
      vegetation and dispersal to distinguish among these factors. Specifically, we
      compared native shrublands with former native shrublands that had been disturbed
      or converted to pasture, resulting in soils progressively more enriched in carbon
      and nutrients. We tested the role of vegetation via active removal, and we
      manipulated dispersal by adding living soil inoculum from undisturbed native
      sites. Soil fungi were tracked for 3 years, with samples taken at ten time points
      from June 2006 to June 2009. We found that soil fungal abundance, richness, and
      community composition responded primarily to soil properties, which in this case
      were a legacy of plant community degradation. In contrast, dispersal had no
      effect on soil fungi. Temporal variation in soil fungi was partly related to
      drought status, yet it was much broader in native sites compared to pastures,
      suggesting some buffering due to the increased soil resources in the pasture
      sites. The persistence of soil fungal communities over 3 years in this study
      suggests that soil properties can act as a strong local environmental filter.
      Largely persistent soil fungal communities also indicate the potential for strong
      biotic resistance and soil legacies, which presents a challenge for both the
      prediction of how fungi respond to environmental change and our ability to
      manipulate fungi in efforts such as ecosystem restoration.

PMID- 24935907
TI  - Maternal experiences of vaginal breech delivery.
AB  - BACKGROUND: The optimal mode of breech birth remains controversial. In Finland, a
      trial of vaginal delivery is possible if strict selection criteria are met. As
      clinical practice in managing vaginal breech birth differs from that in normal
      delivery, the birth experience may also be different. This cohort study compares
      the childbirth experience between term breech and vertex deliveries. METHODS:
      Intended vaginal term breech births from 2008 to October 2012 were included, and
      for every breech delivery, a vertex control was selected. The proportions of
      deliveries ending in a cesarean section and of mothers who had given birth
      vaginally before were equal in both groups. Three hundred eight mothers were sent
      the childbirth experience questionnaire and 170 returned it. RESULTS: The birth
      experience does not differ between breech and vertex births, except for aspects
      with respect to the choice of birthing position. Indications of an even more
      positive experience were observed in the breech group, with the exception of the
      choice of analgesia, but these were not statistically significant. Primiparity,
      emergency cesarean section, infant birth trauma and prolonged hospital stay were
      identified as risk factors for a negative birth experience. CONCLUSION: The birth
      experience of vaginal breech birth seems to be at least as positive as the
      vaginal vertex birth experience.

PMID- 24935908
TI  - Correlation effects in fcc-Fe(x)Ni(1-x) alloys investigated by means of the KKR
      CPA.
AB  - The electronic structure and magnetic properties of the disordered alloy system
      fcc-FexNi1-x (fcc: face centered cubic) have been investigated by means of the
      KKR-CPA (Korringa-Kohn-Rostoker coherent potential approximation) band structure
      method. To investigate the impact of correlation effects, the calculations have
      been performed on the basis of the LSDA (local spin density approximation), the
      LSDA + U as well as the LSDA + DMFT (dynamical mean field theory). It turned out
      that the inclusion of correlation effects hardly changed the spin magnetic
      moments and the related hyperfine fields. The spin-orbit induced orbital magnetic
      moments and hyperfine fields, on the other hand, show a pronounced and element
      specific enhancement. These findings are in full accordance with the results of a
      recent experimental study. 

PMID- 24935909
TI  - Reply: To PMID 23893312.

PMID- 24935910
TI  - I was born following ART: how will I get on at school?
AB  - With an ever-expanding population of children born after in-vitro fertilisation
      (IVF), the widespread use of assisted reproductive techniques (ART) has placed a
      great emphasis on the need to study their long-term outcomes. Indeed, there has
      been concern that mechanisms used in ART may have a detrimental effect on the
      neurocognitive development of these children. Reassuringly, most neurocognitive
      and motor development studies using various assessment scales have generally
      found no differences between intracytoplasmic sperm injection, IVF and naturally
      conceived children. Only a few studies have reported concerns. In terms of
      predictors of intelligence in children, ART appears to have a minimal effect in
      comparison to birth weight, gestational age, socio-economic status, and parental
      educational levels. Nevertheless, further research of higher methodological
      quality in children beyond pre-school age and on newer ART procedures is needed. 

PMID- 24935911
TI  - Abdominal aortic aneurysms with high thrombus signal intensity on magnetic
      resonance imaging are associated with high growth rate.
AB  - OBJECTIVES: A layer of intraluminal thrombus is commonly observed in abdominal
      aortic aneurysms (AAAs). The purpose of this study was to investigate whether
      AAAs with high thrombus signal intensity (SI) at T1-weighted (T1w) magnetic
      resonance imaging (MRI) exhibit a faster aneurysm growth rate. METHODS: This was
      a prospective follow-up study. Patients with a small AAA underwent MRI
      examinations at 6 month intervals. Aneurysm thrombus and psoas muscle SI at the
      point of maximal diameter on T1w images were measured and expressed as a ratio
      (thrombus SI/muscle SI). Based on these measurements, patients were categorized
      into three groups: AAA with relative thrombus SI above (group A) and below (group
      B) the mean relative thrombus SI of 1.20. Patients with AAA without thrombus
      constituted group C. Eight patients were scanned twice within 2 weeks to
      investigate scan-rescan reproducibility. Aneurysm growth rates were expressed as
      the change in maximal cross sectional area (cm(2)). RESULTS: A total of 35
      patients (m/f: 26/9; age 72 +/- 7 years; AAA maximal diameter 4.9 +/- 0.5 cm)
      were included. Mean aneurysm growth rate for patients in group A (n = 11, 1.87
      cm(2)/0.5 year) was two-fold higher than group B (n = 17, 0.78 cm(2)/0.5 year, p
      = .005) and eight-fold higher than group C (n = 7, 0.23 cm(2)/0.5 years, p =
      .004) at 6 months' follow-up. At 12 months' follow-up, the mean aneurysm growth
      rate remained significantly higher in group A (n = 7, 3.03 cm(2)/year) than
      groups B (n = 10, 1.63 cm(2)/year, p = .03) and C (n = 7, 0.73 cm(2)/year, p =
      .004). The reproducibility for thrombus SI measurements was found to be high with
      a coefficient of variation of 6.2%. Aneurysm maximal cross-sectional area at
      baseline was not significantly different for the three groups. CONCLUSIONS:
      Abdominal aortic aneurysms with high thrombus SI on T1w MR images are associated
      with higher aneurysm growth rates.

PMID- 24935912
TI  - Anemia, an independent predictive factor for amputation and mortality in patients
      hospitalized for peripheral artery disease.
AB  - OBJECTIVES: Anemia is associated with poorer outcome in coronary artery disease
      (CAD) and heart failure (HF), but data on patients with peripheral artery disease
      (PAD) are scarce, especially regarding the local (limb) prognosis. It was
      hypothesized that anemia is associated with poorer prognosis in patients
      hospitalized for PAD, and this relationship would be proportional to the severity
      of the anemia. DESIGN: Prospective cohort study. MATERIALS: The Cohorte des
      Patients Arteritiques (COPART) is a multicenter registry of patients hospitalized
      for PAD in three university hospitals in southwestern France. METHODS: Clinical
      and biological data were collected at entry. Patients were followed up to 1 year.
      Anemia was defined by Hb < 8.2 mmol/L in men and <7.6 mmol/L in women. The
      primary outcome was 1-year survival free from major amputation. The secondary
      outcome was 1-year major amputation. RESULTS: Data of 925 consecutive patients
      (70.7 +/- 12.8 years, 29.2% females) were analyzed. Patients were hospitalized
      either for revascularization or medical therapy, with Rutherford categories 3
      (25%), 4 (9.1%), 5 or 6 (55.1%) as well as acute limb ischemia (10.8%). Anemia
      was present in 471 patients (50.9%). These patients were significantly older,
      with higher rates of hypertension, diabetes, clinical CAD, HF, chronic kidney
      disease, and cancer, and with lower rates of smoking and dyslipidemia than their
      counterparts (p < .05 for all). In multivariate models, anemia was significantly
      and independently associated (p < 0.001) with death and amputation (HR 1.44; 95%
      CI 1.15-1.80) with similar findings for secondary outcomes. A lower level of
      hemoglobin is associated with a higher risk of mortality and amputation (HR 1.20;
      95% CI 1.09-1.32). CONCLUSION: Anemia and its severity are independent predictors
      of mortality and limb loss in patients hospitalized for PAD.

PMID- 24935913
TI  - Re. 'Ultrasound measurement for abdominal aortic aneurysm screening: a direct
      comparison of the three leading methods'.

PMID- 24935914
TI  - Commentary on "MRI-derived arterial peak flow in peripheral arterial disease:
      towards a standardized measurement".

PMID- 24935916
TI  - PARduino: a simple and inexpensive device for logging photosynthetically active
      radiation.
AB  - Photosynthetically active radiation (PAR, 400-700 nm) is one of the primary
      controls of forest carbon and water relations. In complex terrain, PAR has high
      spatial variability. Given the high cost of commercial datalogging equipment,
      spatially distributed measurements of PAR have been typically modeled using
      geographic coordinates and terrain indices. Here, we present a design for a low
      cost, field-deployable device for measuring and recording PAR built around an
      Arduino microcontroller-named PARduino. PARduino provides for widely distributed
      sensor arrays and tests the feasibility of using open-source, hobbyist-grade
      electronics for collecting scientific data. PARduino components include a quantum
      sensor, an EME Systems signal converter/amplifier and an Arduino Pro Mini
      microcontroller. Additional components include a real-time clock, a microSD Flash
      memory card and a custom printed circuit board. The components were selected for
      ease of assembly. We found strong agreement between the PARduino datalogger
      system and National Institute of Standards and Technology traceable sensors
      logged by an industry standard datalogger (slope = 0.99, SE < 0.01, P < 0.01;
      intercept = - 14.84, SE = 0.78, P < 0.01). The average difference between the two
      systems was 22.0 umol m(-2) s(-1) with PARduino typically underestimating PAR.
      The average percentage difference between systems was 3.49%. On average, PARduino
      performed within the factory absolute calibration of the PAR sensor; however,
      larger errors occurred at low PAR levels. Using open-source technologies such as
      this can make it possible to develop a spatially distributed sensor network
      within the constraints of a typical research budget. 

PMID- 24935915
TI  - A Bayesian mixed-treatment comparison meta-analysis of treatments for alcohol
      dependence and implications for planning future trials.
AB  - BACKGROUND: Several treatments for alcohol dependence have been tested in
      randomized controlled trials, giving rise to systematic reviews with a network of
      evidence structure, or mixed treatment comparisons (MTCs). Within the network,
      there are few direct comparisons of active treatments. Thus far, this network has
      not been adequately analyzed. For example, "indirect comparisons" between
      treatments (e.g., the comparison of treatments B:C obtained via estimates from
      A:B and A:C trials) have not been incorporated into estimates of treatment
      effects. This has implications for the planning of future randomized controlled
      trials. METHODS: We applied recent developments in Bayesian MTC meta-analysis to
      analyze the network of evidence. Using these results, we proposed a methodology
      to inform, design, and power a hypothetical trial in the context of an updated
      meta-analysis for treatments that have been infrequently compared and therefore
      whose effect sizes are not well informed by a meta-analysis. RESULTS: An MTC meta
      analysis provides more accurate estimates than a pairwise meta-analysis and
      uncovers decisive differences between active treatments that have been
      infrequently directly compared. Weighting across all outcomes indicates that a
      combination (naltrexone + acamprosate) treatment has the highest posterior
      probability of being the "best" treatment. If a new clinical trial were to be
      conducted of a combination therapy versus acamprosate alone, there is no feasible
      sample size that would result in a decisive meta-analysis. CONCLUSIONS: An MTC
      meta-analysis should be used to estimate treatment effects in networks in which
      direct and indirect evidence are consistent and to inform the design of future
      studies.

PMID- 24935917
TI  - Determination of zofenopril and its active metabolite in human plasma using high
      performance liquid chromatography combined with a triple-quadruple tandem mass
      spectrometer.
AB  - A simple, selective and sensitive LC-MS-MS method has been developed and
      validated to simultaneously quantify zofenopril and its active metabolite
      zofenoprilat in human plasma, using diazepam as internal standard. 1,4
      Dithiothreitol was used as a reducer to release and stabilize the thiol group of
      zofenoprilat from dimer and mixed forms with endogenous thiols in the treatment
      of plasma samples. After a liquid-liquid extraction with methyl tert-butyl ether
      under acidic conditions, the post-treatment samples were analyzed on an Agilent
      ZORBAX Eclipse XDB-C8 column interfaced with a triple-quadruple tandem mass
      spectrometer using positive electrospray ionization. A solution of methanol and
      0.1% formic acid solution (85 : 15, v/v) was used as the isocratic mobile phase
      with a flow rate of 0.2 mL/min. The method was validated to demonstrate the
      specificity, lower limit of quantitation, accuracy and precision of measurements.
      The validated LC-MS-MS method has been successfully applied to study the
      pharmacokinetics of zofenopril calcium in healthy Chinese volunteers. 

PMID- 24935918
TI  - Solid-phase extraction-based ultra-sensitive detection of four lipophilic marine
      biotoxins in bivalves by high-performance liquid chromatography-tandem mass
      spectrometry.
AB  - A solid-phase extraction (SPE) method for ultra-sensitive determination of four
      lipophilic marine biotoxins in bivalve samples by coupling high-performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) was developed.
      Azaspiracid-2 (AZA2), pectenotoxins-2, spirolide (SPX) and gymnodimine were
      simultaneously determined by HPLC-MS-MS in a positive multiple reaction
      monitoring mode. Separation was achieved on a reversed-phase C18 column with an
      acetonitrile-water gradient containing formic acid. During the analysis, solvent
      effects on the analytes were eliminated by using 1 : 1 water-methanol as
      dissolving solvent instead of pure methanol. Matrix effects in post-SPE extract
      and crude extract were seriously evaluated. Increased matrix effects in post-SPE
      extract countervailed the concentration purpose to some extent. The limits of
      detection of the SPE-HPLC-MS-MS method were determined to be in the range of
      0.013-0.085 ug kg(-1), and the linear range of the method was in the range of
      0.128-55.2 ng mL(-1) for the detected toxins. The proposed method was validated
      in terms of linearity (matrix-matched standard curves), precision, recovery,
      repeatability and limits of quantification. The recoveries of fortified samples
      at three different concentration levels were satisfactory, and the intra- and
      interday precisions were <7 and 10%, respectively.Several bivalve samples were
      analyzed to demonstrate the applicability of the proposed method. Different
      target toxins were detected in different kind of bivalves. Among them, AZA2 and
      SPX1 were first detected in Chinese shellfish. The levels of detected toxins were
      below the current European Union regulatory limits. 

PMID- 24935919
TI  - Unilateral pulmonary oedema in dextrocardia.

PMID- 24935920
TI  - An unusual case of right-sided heart failure caused by giant sinus of Valsalva
      aneurysm obstructing right ventricular outflow tract.

PMID- 24935921
TI  - Myotonic dystrophy: time for evidence-based therapy.

PMID- 24935922
TI  - Apurinic/apyrimidinic endonuclease 2 regulates the expansion of germinal centers
      by protecting against activation-induced cytidine deaminase-independent DNA
      damage in B cells.
AB  - Activation-induced cytidine deaminase (AID) initiates a process generating DNA
      mutations and breaks in germinal center (GC) B cells that are necessary for
      somatic hypermutation and class-switch recombination. GC B cells can "tolerate"
      DNA damage while rapidly proliferating because of partial suppression of the DNA
      damage response by BCL6. In this study, we develop a model to study the response
      of mouse GC B cells to endogenous DNA damage. We show that the base excision
      repair protein apurinic/apyrimidinic endonuclease (APE) 2 protects activated B
      cells from oxidative damage in vitro. APE2-deficient mice have smaller GCs and
      reduced Ab responses compared with wild-type mice. DNA double-strand breaks are
      increased in the rapidly dividing GC centroblasts of APE2-deficient mice, which
      activate a p53-independent cell cycle checkpoint and a p53-dependent apoptotic
      response. Proliferative and/or oxidative damage and AID-dependent damage are
      additive stresses that correlate inversely with GC size in wild-type, AID-, and
      APE2-deficient mice. Excessive double-strand breaks lead to decreased expression
      of BCL6, which would enable DNA repair pathways but limit GC cell numbers. These
      results describe a nonredundant role for APE2 in the protection of GC cells from
      AID-independent damage, and although GC cells uniquely tolerate DNA damage, we
      find that the DNA damage response can still regulate GC size through pathways
      that involve p53 and BCL6. 

PMID- 24935923
TI  - Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and
      DAP12.
AB  - The NKG2 family of NK receptors includes activating and inhibitory members. With
      the exception of the homodimer-forming NKG2D, NKG2 receptors recognize the
      nonclassical MHC class I molecule HLA-E, and they can be subdivided into two
      groups: those that associate with and signal through DAP12 to activate cells, and
      those that contain an ITIM motif to promote inhibition. The function of NKG2
      family member NKG2E is unclear in humans, and its surface expression has never
      been conclusively established, largely because there is no Ab that binds
      specifically to NKG2E. Seeking to determine a role for this molecule, we chose to
      investigate its expression and ability to form complexes with intracellular
      signaling molecules. We found that NKG2E was capable of associating with CD94 and
      DAP12 but that the complex was retained intracellularly at the endoplasmic
      reticulum instead of being expressed on cell surfaces, and that this localization
      was dependent on a sequence of hydrophobic amino acids in the extracellular
      domain of NKG2E. Because this particular sequence has emerged and been conserved
      selectively among higher order primates evolutionarily, this observation raises
      the intriguing possibility that NKG2E may function as an intracellular protein. 

PMID- 24935924
TI  - Adrenocortical scavenger receptor class B type I deficiency exacerbates endotoxic
      shock and precipitates sepsis-induced mortality in mice.
AB  - Scavenger receptor class B type I (SR-BI)-deficient mice display reduced survival
      to endotoxic shock and sepsis. The understanding of the mechanisms underlying SR
      BI protection has been hampered by the large spectrum of SR-BI functions and
      ligands. It notably plays an important role in the liver in high-density
      lipoprotein metabolism, but it is also thought to participate in innate immunity
      as a pattern recognition receptor for bacterial endotoxins, such as LPS. In this
      study, we sought to determine the tissue-specific contribution of SR-BI in the
      hyperinflammatory response and high mortality rates observed in SR-BI(-/-) mice
      in endotoxicosis or sepsis. Restoring plasma levels of high-density lipoprotein,
      which are critical lipoproteins for LPS neutralization, did not improve acute
      outcomes of LPS injection in SR-BI(-/-) mice. Mice deficient for SR-BI in
      hepatocytes, endothelial cells, or myeloid cells were not more susceptible to LPS
      induced death. However, if SR-BI ablation in hepatocytes led to a moderate
      increase in systemic inflammatory markers, SR-BI deficiency in myeloid cells was
      associated with an anti-inflammatory effect. Finally, mice deficient for SR-BI in
      the adrenal cortex, where the receptor provides lipoprotein-derived cholesterol,
      had impaired secretion of glucocorticoids in response to stress. When exposed to
      an endotoxin challenge, these mice exhibited an exacerbated systemic and local
      inflammatory response, reduced activation of atrophy genes in muscle, and high
      lethality rate. Furthermore, polymicrobial sepsis induced by cecal ligature and
      puncture resulted in early death of these animals. Our study clearly demonstrates
      that corticoadrenal SR-BI is a critical element of the hypothalamic-pituitary
      adrenal axis to provide effective glucocorticoid-dependent host defense after an
      endotoxic shock or bacterial infection. 

PMID- 24935925
TI  - Tryptophan catabolism restricts IFN-gamma-expressing neutrophils and Clostridium
      difficile immunopathology.
AB  - The interplay between Clostridium difficile and the host's metabolome is believed
      to influence the severity of infection. However, the mechanism for this
      phenomenon remains unclear. In this study, we model one of these metabolic
      pathways by focusing on tryptophan metabolism in the host. We found that
      inhibition of tryptophan catabolism in IDO1-knockout mice led to increased
      mucosal destruction, cecal hemorrhage, and increased production of IFN-gamma in
      response to C. difficile infection, but no significant change in mucosal effector
      or regulatory T cell numbers or IL-10 mRNA expression. The increased
      immunopathology in infected IDO1-knockout mice was associated with a lower C.
      difficile burden and an increased percentage of IFN-gamma-expressing neutrophils.
      We further demonstrated the ability of kynurenine to induce apoptosis in bone
      marrow-derived neutrophils, whereas the presence of tryptophan reversed this
      effect, providing a possible mechanism for the increased neutrophil accumulation
      in IDO1(-/-) mice. We conclude that C. difficile induces tryptophan catabolism in
      cecal lamina propria cells, which restricts C. difficile-associated
      immunopathology and the accumulation of IFN-gamma-expressing neutrophils. This
      might represent a self-regulatory mechanism for neutrophils, via the IFN-gamma
      IDO1 pathway, to restrict their own accumulation during infection. These findings
      have important clinical implications because IDO inhibitors are used to treat
      cancer in clinical trials (in patients particularly susceptible to getting C.
      difficile infection), and treatment with IDO1 inhibitors may exacerbate the
      severity of C. difficile colitis. 

PMID- 24935927
TI  - Molecular determinants of agonist and antagonist signaling through the IL-36
      receptor.
AB  - The IL-1 family consists of 11 cytokines that control a complex network of
      proinflammatory signals critical for regulating immune responses to infections.
      They also play a central role in numerous chronic inflammatory disorders.
      Accordingly, inhibiting the activities of these cytokines is an important
      therapeutic strategy for treating autoimmune diseases and lymphomas. Agonist
      cytokines in the IL-1 family activate signaling by binding their cognate receptor
      and then recruiting a receptor accessory protein. Conversely, antagonist
      cytokines bind their cognate receptor but prohibit recruitment of receptor
      accessory protein, which precludes functional signaling complexes. The IL-36
      subfamily of cytokines is the most diverse, including three agonists and at least
      one antagonist, and is the least well-characterized group within this family.
      Signaling through the IL-36 receptor directly stimulates dendritic cells and
      primes naive CD4 T cells for Th1 responses. Appropriately balanced IL-36
      signaling is a critical determinant of skin and lung health. IL-36 signaling has
      been presumed to function analogously to IL-1 signaling. In this study, we have
      defined molecular determinants of agonist and antagonist signaling through the IL
      36 receptor. We present the crystal structure of IL-36gamma, which, to our
      knowledge, is the first reported structure of an IL-36 agonist. Using this
      structure as a guide, we designed a comprehensive series of IL-36
      agonist/antagonist chimeric proteins for which we measured binding to the IL-36
      receptor/IL-1 receptor accessory protein complex and functional activation and
      inhibition of signaling. Our data reveal how the fine specificity of IL-36
      signaling is distinct from that of IL-1. 

PMID- 24935926
TI  - PILRalpha negatively regulates mouse inflammatory arthritis.
AB  - Paired Ig-like type 2 receptor (PILR)alpha inhibitory receptor and its
      counterpart PILRbeta activating receptor are coexpressed on myeloid cells. In
      this article, we report that PILRalpha, but not PILRbeta, is elevated in human
      rheumatoid arthritis synovial tissue and correlates with inflammatory cell
      infiltration. Pilralpha(-/-) mice produce more pathogenic cytokines during
      inflammation and are prone to enhanced autoimmune arthritis. Correspondingly,
      engaging PILRalpha with anti-PILRalpha mAb ameliorates inflammation in mouse
      arthritis models and suppresses the production of proinflammatory cytokines. Our
      studies suggest that PILRalpha mediates an important inhibitory pathway that can
      dampen inflammatory responses. 

PMID- 24935929
TI  - Autotaxin produced by stromal cells promotes LFA-1-independent and Rho-dependent
      interstitial T cell motility in the lymph node paracortex.
AB  - T cells exhibit high-speed migration within the paracortical T zone of lymph
      nodes (LNs) as they scan cognate Ags displayed by dendritic cells in the tissue
      microenvironment supported by the network of stromal cells. Although intranodal T
      cell migration is controlled in part by chemokines and LFA-1/ICAM-1, the
      mechanisms underlying their migratory activity independent of these factors
      remain to be elucidated. In this study, we show that LN stromal cells
      constitutively express autotaxin (ATX), an ectoenzyme that is important for the
      generation of lysophosphatidic acid (LPA). Importantly, CCL21(+) stromal cells in
      the T zone produced and immobilized ATX on their cell surface. Two-photon imaging
      using LN tissue slices revealed that pharmacological inhibition of ATX or LPA
      receptors significantly reduced T cell migration, and this was further
      exacerbated by blockage of Galphai signaling or LFA-1. Therefore, T cell motility
      mediated by the ATX-LPA axis was independent of Galphai and LFA-1. LPA induced
      slow intermittent movement of T cells in vitro in a LFA-1-independent manner and
      enhanced CCL21-induced migration. Moreover, LPA and CCL21 cooperatively augmented
      RhoA activity in T cells, which was necessary for efficient intranodal T cell
      migration via the downstream ROCK-myosin II pathway. Taken together, T zone
      stromal cells control optimal migratory behavior of T cells via multiple
      signaling cues mediated by chemokines and ATX/LPA. 

PMID- 24935930
TI  - Inhibition of PI3Kdelta reduces kidney infiltration by macrophages and
      ameliorates systemic lupus in the mouse.
AB  - Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease
      generated and maintained throughout life by autoreactive T and B cells. Class I
      phosphoinositide 3-kinases (PI3K) are heterodimers composed of a regulatory and a
      catalytic subunit that catalyze phosphoinositide-3,4,5-P3 formation and regulate
      cell survival, migration, and division. Activity of the PI3Kdelta isoform is
      enhanced in human SLE patient PBLs. In this study, we analyzed the effect of
      inhibiting PI3Kdelta in MRL/lpr mice, a model of human SLE. We found that
      PI3Kdelta inhibition ameliorated lupus progression. Treatment of these mice with
      a PI3Kdelta inhibitor reduced the excessive numbers of CD4(+) effector/memory
      cells and B cells. In addition, this treatment reduced serum TNF-alpha levels and
      the number of macrophages infiltrating the kidney. Expression of inactive
      PI3Kdelta, but not deletion of the other hematopoietic isoform PI3Kgamma, reduced
      the ability of macrophages to cross the basement membrane, a process required to
      infiltrate the kidney, explaining MRL/lpr mice improvement by pharmacologic
      inhibition of PI3Kdelta. The observations that p110delta inhibitor prolonged
      mouse life span, reduced disease symptoms, and showed no obvious secondary
      effects indicates that PI3Kdelta is a promising target for SLE. 

PMID- 24935928
TI  - Human NK cells licensed by killer Ig receptor genes have an altered cytokine
      program that modifies CD4+ T cell function.
AB  - NK cells are innate immune cells known for their cytolytic activities toward
      tumors and infections. They are capable of expressing diverse killer Ig-like
      receptors (KIRs), and KIRs are implicated in susceptibility to Crohn's disease
      (CD), a chronic intestinal inflammatory disease. However, the cellular mechanism
      of this genetic contribution is unknown. In this study, we show that the
      "licensing" of NK cells, determined by the presence of KIR2DL3 and homozygous HLA
      C1 in host genome, results in their cytokine reprogramming, which permits them to
      promote CD4(+) T cell activation and Th17 differentiation ex vivo. Microfluidic
      analysis of thousands of NK single cells and bulk secretions established that
      licensed NK cells are more polarized to proinflammatory cytokine production than
      unlicensed NK cells, including production of IFN-gamma, TNF-alpha, CCL-5, and MIP
      1beta. Cytokines produced by licensed NK augmented CD4(+) T cell proliferation
      and IL-17A/IL-22 production. Ab blocking indicated a primary role for IFN-gamma,
      TNF-alpha, and IL-6 in the augmented T cell-proliferative response. In
      conclusion, NK licensing mediated by KIR2DL2/3 and HLA-C1 elicits a novel NK
      cytokine program that activates and induces proinflammatory CD4(+) T cells,
      thereby providing a potential biologic mechanism for KIR-associated
      susceptibility to CD and other chronic inflammatory diseases. 

PMID- 24935931
TI  - gp49B-mediated negative regulation of antibody production by memory and marginal
      zone B cells.
AB  - The rapid Ab responses observed after primary and secondary immunizations are
      mainly derived from marginal zone (MZ) and memory B cells, respectively, but it
      is largely unknown how these responses are negatively regulated. Several
      inhibitory receptors have been identified and their roles have been studied, but
      mainly on follicular B cells and much less so on MZ B, and never on memory B
      cells. gp49B is an Ig superfamily member that contains two ITIMs in its
      cytoplasmic tail, and it has been shown to negatively regulate mast cell,
      macrophage, and NK cell responses. In this study, we demonstrate that gp49B is
      preferentially expressed on memory and MZ B cells. We show that gp49B(-/-) mice
      produce more IgM after a primary immunization and more IgM and IgG1 after a
      secondary immunization than gp49B(+/+) mice in T cell-dependent immune responses.
      Memory and MZ B cells from gp49B(-/-) mice also produce more Abs upon in vitro
      stimulation with CD40 than those from gp49B(+/+) mice. The in vitro IgM
      production by MZ B cells from gp49B(+/+), but not gp49B(-/-), mice is suppressed
      by interaction with a putative gp49B ligand, the integrin alphavbeta3
      heterodimer. In addition, gp49B(-/-) mice exhibited exaggerated IgE production in
      the memory recall response. These results suggest that plasma cell development
      from memory and MZ B cells, as well as subsequent Ab production, are suppressed
      via gp49B. In memory B cells, this suppression also prevents excessive IgE
      production, thus curtailing allergic diseases. 

PMID- 24935932
TI  - The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose
      tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects.
AB  - OBJECTIVE: Inhibition of dipeptidyl peptidase 4 (DPP4) is thought to intensify
      the physiological effects of the incretin hormones. We investigated the effects
      of DPP4 inhibition on plasma levels of glucose-dependent insulinotropic
      polypeptide (GIP), glucagon-like peptide 1 (GLP1), incretin effect, glucose
      tolerance, gastrointestinal-mediated glucose disposal (GIGD) and gastric emptying
      in healthy subjects. DESIGN: A randomised, controlled and open-labelled study.
      METHODS: Ten healthy subjects (six women; age, 40+/-5 years (mean+/-s.e.m.); BMI,
      24+/-3 kg/m(2); fasting plasma glucose, 5.1+/-0.2 mmol/l and HbA1c, 34+/-1
      mmol/mol (5.3+/-0.1%)) were randomised to two-paired study days comprising a 4-h
      50 g oral glucose tolerance test (OGTT) with paracetamol (A) and an isoglycaemic
      intravenous (i.v.) glucose infusion (B), with (A1+B1) and without (A2+B2)
      preceding administration of the DPP4 inhibitor sitagliptin. RESULTS: Isoglycaemia
      was obtained in all subjects on the paired study days. Significant increases in
      fasting levels and OGTT-induced responses of active GLP1 and GIP were seen after
      DPP4 inhibition. No significant impact of DPP4 inhibition on fasting plasma
      glucose (5.1+/-0.1 vs 4.9+/-0.1 mmol/l, P=0.3), glucose tolerance (area under the
      curve (AUC) for plasma glucose, 151+/-35 vs 137+/-26 mmol/l*min, P=0.7) or peak
      plasma glucose during OGTT (8.5+/-0.4 vs 8.1+/-0.3 mmol/l, P=0.3) was observed.
      Neither incretin effect (40+/-9% (without DPP4 inhibitor) vs 40+/-7% (with DPP4
      inhibitor), P=1.0), glucagon responses (1395+/-165 vs 1223+/-195 pmol/l*min,
      P=0.41), GIGD (52+/-4 vs 56+/-5%, P=0.40) nor gastric emptying (Tmax for plasma
      paracetamol: 86+/-9 vs 80+/-12 min, P=0.60) changed following DPP4 inhibition.
      CONCLUSIONS: These results suggest that acute increases in active incretin
      hormone levels do not affect glucose tolerance, GIGD, incretin effect, glucagon
      responses or gastric emptying in healthy subjects.

PMID- 24935933
TI  - The onset time of amiodarone-induced thyrotoxicosis (AIT) depends on AIT type.
AB  - OBJECTIVE: Considering the different pathogenic mechanisms of the two main forms
      of amiodarone-induced thyrotoxicosis (AIT), we ascertained whether this results
      in a different onset time as well. DESIGN AND METHODS: We retrospectively
      analyzed the clinical records of 200 consecutive AIT patients (157 men and 43
      women; mean age 62.2+/-12.6 years) referred to our Department from 1987 to 2012.
      The onset time of AIT was defined as the time elapsed from the beginning of
      amiodarone therapy and the first diagnosis of thyrotoxicosis, expressed in
      months. Factors associated with the onset time of AIT were evaluated by
      univariate and multivariate analyses. RESULTS: The median onset time of
      thyrotoxicosis was 3.5 months (95% CI 2-6 months) in patients with type 1 AIT
      (AIT1) and 30 months (95% CI 27-32 months, P<0.001) in those with type 2 AIT
      (AIT2). Of the total number of patients, 5% with AIT1 and 23% with AIT2 (P=0.007)
      developed thyrotoxicosis after amiodarone withdrawal. Factors affecting the onset
      time of thyrotoxicosis were the type of AIT and thyroid volume (TV). CONCLUSIONS:
      The different pathogenic mechanisms of the two forms of AIT account for different
      onset times of thyrotoxicosis in the two groups. Patients with preexisting
      thyroid abnormalities (candidate to develop AIT1) may require a stricter follow
      up during amiodarone therapy than those usually recommended. In AIT1, the onset
      of thyrotoxicosis after amiodarone withdrawal is rare, while AIT2 patients may
      require periodic tests for thyroid function longer after withdrawing amiodarone.

PMID- 24935934
TI  - A role for descending auditory cortical projections in songbird vocal learning.
AB  - Many learned motor behaviors are acquired by comparing ongoing behavior with an
      internal representation of correct performance, rather than using an explicit
      external reward. For example, juvenile songbirds learn to sing by comparing their
      song with the memory of a tutor song. At present, the brain regions subserving
      song evaluation are not known. In this study, we report several findings
      suggesting that song evaluation involves an avian 'cortical' area previously
      shown to project to the dopaminergic midbrain and other downstream targets. We
      find that this ventral portion of the intermediate arcopallium (AIV) receives
      inputs from auditory cortical areas, and that lesions of AIV result in
      significant deficits in vocal learning. Additionally, AIV neurons exhibit fast
      responses to disruptive auditory feedback presented during singing, but not
      during nonsinging periods. Our findings suggest that auditory cortical areas may
      guide learning by transmitting song evaluation signals to the dopaminergic
      midbrain and/or other subcortical targets. 

PMID- 24935935
TI  - The role of photorespiration during the evolution of C4 photosynthesis in the
      genus Flaveria.
AB  - C4 photosynthesis represents a most remarkable case of convergent evolution of a
      complex trait, which includes the reprogramming of the expression patterns of
      thousands of genes. Anatomical, physiological, and phylogenetic and analyses as
      well as computational modeling indicate that the establishment of a
      photorespiratory carbon pump (termed C2 photosynthesis) is a prerequisite for the
      evolution of C4. However, a mechanistic model explaining the tight connection
      between the evolution of C4 and C2 photosynthesis is currently lacking. Here we
      address this question through comparative transcriptomic and biochemical analyses
      of closely related C3, C3-C4, and C4 species, combined with Flux Balance Analysis
      constrained through a mechanistic model of carbon fixation. We show that C2
      photosynthesis creates a misbalance in nitrogen metabolism between bundle sheath
      and mesophyll cells. Rebalancing nitrogen metabolism requires anaplerotic
      reactions that resemble at least parts of a basic C4 cycle. Our findings thus
      show how C2 photosynthesis represents a pre-adaptation for the C4 system, where
      the evolution of the C2 system establishes important C4 components as a side
      effect. 

PMID- 24935937
TI  - Role of inflammation and the angiotensin type 2 receptor in the regulation of
      arterial pressure during pregnancy in mice.
AB  - During normal pregnancy the renin-angiotensin system is activated, yet pregnant
      women are resistant to the pressor effects of angiotensin II. Our aim was to
      determine the role of the angiotensin type 2 receptor (AT2R) in the regulation of
      arterial pressure, natriuresis, and immune cell infiltration during pregnancy.
      Mean arterial pressure was measured via telemetry, and flow cytometry was used to
      enumerate immune cell infiltration in 14-week-old wild-type and AT2R knockout
      mice during gestation. In wild-type mice, mean arterial pressure decreased during
      gestation, reaching a nadir at gestational day 9 (-6+/-2 mm Hg) and returned to
      near preconception levels during late gestation. In AT2R-deficient mice, the
      midgestational decrease in mean arterial pressure was absent. Furthermore, mean
      arterial pressure was significantly increased during late gestation compared with
      wild-type mice (~10 mm Hg). As expected, circulating immune cell activation was
      suppressed during pregnancy. However, this response was absent in AT2R-deficient
      mice. While renal immune cell infiltration was similar between the genotypes,
      there was a significant T cell phenotypic switch toward a proinflammatory T
      helper 1 phenotype in AT2R-deficient mice. These data indicate that the AT2R
      plays an important role in arterial pressure regulation and may modulate T cell
      activation and renal cytokine production during pregnancy. Therefore, deficits in
      AT2R expression may contribute to pregnancy-induced hypertension and thus
      represents a potential therapeutic target. 

PMID- 24935936
TI  - Allosteric inhibition of a stem cell RNA-binding protein by an intermediary
      metabolite.
AB  - Gene expression and metabolism are coupled at numerous levels. Cells must sense
      and respond to nutrients in their environment, and specialized cells must
      synthesize metabolic products required for their function. Pluripotent stem cells
      have the ability to differentiate into a wide variety of specialized cells. How
      metabolic state contributes to stem cell differentiation is not understood. In
      this study, we show that RNA-binding by the stem cell translation regulator
      Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9
      monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA
      Recognition Motif (RRM) and induces a conformational change that prevents RNA
      association. Musashi proteins are critical for development of the brain, blood,
      and epithelium. We identify stearoyl-CoA desaturase-1 as a MSI1 target, revealing
      a feedback loop between omega-9 fatty acid biosynthesis and MSI1 activity. We
      propose that other RRM proteins could act as metabolite sensors to couple gene
      expression changes to physiological state. 

PMID- 24935939
TI  - Added predictive value of night-time blood pressure variability for
      cardiovascular events and mortality: the Ambulatory Blood Pressure-International
      Study.
AB  - The association of ambulatory blood pressure (BP) variability with mortality and
      cardiovascular events is controversial. To investigate whether BP variability
      predicts cardiovascular events and mortality in hypertension, we analyzed 7112
      untreated hypertensive participants (3996 men) aged 52+/-15 years enrolled in 6
      prospective studies. Median follow-up was 5.5 years. SD of night-time BP was
      positively associated with age, body mass index, smoking, diabetes mellitus, and
      average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP
      variability was an independent predictor of all-cause mortality (systolic,
      P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and
      cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was
      not an independent predictor of outcomes in any model. In fully adjusted models,
      a night-time systolic BP SD of >=12.2 mm Hg was associated with a 41% greater
      risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a
      59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The
      corresponding values for a diastolic BP SD of >=7.9 mm Hg were 48%, 132%, and
      77%. The addition of night-time BP variability to fully adjusted models had a
      significant impact on risk reclassification and integrated discrimination for all
      outcomes (relative integrated discrimination improvement for systolic BP
      variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular
      death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all
      cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP
      variability to models of long-term outcomes improved the ability to stratify
      appropriately patients with hypertension among risk categories defined by
      standard clinical and laboratory variables. 

PMID- 24935940
TI  - Catheter-based renal denervation for resistant hypertension: 12-month results of
      the EnligHTN I first-in-human study using a multielectrode ablation system.
AB  - Renal denervation has emerged as a novel approach for the treatment of patients
      with drug-resistant hypertension. To date, only limited data have been published
      using multielectrode radiofrequency ablation systems. In this article, we present
      the 12-month data of EnligHTN I, a first-in-human study using a multielectrode
      ablation catheter. EnligHTN I enrolled 46 patients (average age, 60+/-10 years;
      on average 4.7+/-1.0 medications) with drug-resistant hypertension. Eligible
      patients were on >=3 antihypertensive medications and had a systolic blood
      pressure (BP) >=160 mm Hg (>=150 mm Hg for diabetics). Bilateral renal artery
      ablation was performed using a percutaneous femoral approach and standardized
      techniques. The average baseline office BP was 176/96 mm Hg, average 24-hour
      ambulatory BP was 150/83 mm Hg, and average home BP was 158/90 mm Hg. The average
      reductions (mm Hg) at 1, 3, 6, and 12 months were as follows: office: -28/-10, 
      27/-10, -26/-10, and -27/-11 mm Hg (P<0.001 for all); 24-hour ambulatory: -10/-5,
      -10/-5, -10/-6 (P<0.001 for all), and -7/-4 for 12 months (P<0.0094). Reductions
      in home measurements (based on 2-week average) were -9/-4, -8/-5,-10/-7, and -11/
      6 mm Hg (P<0.001 at 12 months). At 12 months, there were no signals of worsening
      renal function and no new serious or life-threatening adverse events. One patient
      with baseline nonocclusive renal artery stenosis progressed to 75% diameter
      stenosis, requiring renal artery stenting. The 12-month data continue to
      demonstrate safety and efficacy of the EnligHTN ablation system in patients with
      drug-resistant hypertension. Home BP measurements parallel measurements obtained
      with 24-hour ambulatory monitoring. 

PMID- 24935938
TI  - Sex-specific T-cell regulation of angiotensin II-dependent hypertension.
AB  - Studies suggest T cells modulate arterial pressure. Because robust sex
      differences exist in the immune system and in hypertension, we investigated sex
      differences in T-cell modulation of angiotensin II-induced increases in mean
      arterial pressure in male (M) and female (F) wild-type and recombination
      activating-gene-1-deficient (Rag1(-/-)) mice. Sex differences in peak mean
      arterial pressure in wild-type were lost in Rag1(-/-) mice (mm Hg: wild-type-F,
      136+/-4.9 versus wild-type-M, 153+/-1.7; P<0.02; Rag1(-/-)-F, 135+/-2.1 versus
      Rag1(-/-)-M, 141+/-3.8). Peak mean arterial pressure was 13 mm Hg higher after
      adoptive transfer of male (CD3(M)->Rag1(-/-)-M) versus female (CD3(F)->Rag1(-/-)
      M) T cells. CD3(M)->Rag1(-/-)-M mice exhibited higher splenic frequencies of
      proinflammatory interleukin-17A (2.4-fold) and tumor necrosis factor-alpha (2.2
      fold)-producing T cells and lower plasma levels (13-fold) and renal mRNA
      expression (2.4-fold) of interleukin-10, whereas CD3(F)->Rag1(-/-)-M mice
      displayed a higher activation state in general and T-helper-1-biased renal
      inflammation. Greater T-cell infiltration into perivascular adipose tissue and
      kidney associated with increased pressor responses to angiotensin II if the T
      cell donor was male but not female and these sex differences in T-cell subset
      expansion and tissue infiltration were maintained for 7 to 8 weeks within the
      male host. Thus, the adaptive immune response and role of pro- and anti
      inflammatory cytokine signaling in hypertension are distinct between the sexes
      and need to be understood to improve therapeutics for hypertension-associated
      disease in both men and women. 

PMID- 24935941
TI  - Regulation of renin secretion and arterial pressure during prolonged baroreflex
      activation: influence of salt intake.
AB  - Chronic electric activation of the carotid baroreflex produces sustained
      reductions in sympathetic activity and arterial pressure and is currently being
      evaluated as antihypertensive therapy for patients with resistant hypertension.
      However, the influence of variations in salt intake on blood pressure lowering
      during baroreflex activation (BA) has not yet been determined. As the sensitivity
      of arterial pressure to salt intake is linked to the responsiveness of renin
      secretion, we determined steady-state levels of arterial pressure and
      neurohormonal responses in 6 dogs on low, normal, and high salt intakes (5, 40,
      450 mmol/d, respectively) under control conditions and during a 7-day constant
      level of BA. Under control conditions, there was no difference in mean arterial
      pressure at low (92+/-1) and normal (92+/-2 mm Hg) sodium intakes, but pressure
      increased 9+/-2 mm Hg during high salt. Plasma renin activity (2.01+/-0.23,
      0.93+/-0.20, 0.01+/-0.01 ng angiotensin I/mL/h) and plasma aldosterone (10.3+/
      1.9, 3.5+/-0.5, 1.7+/-0.1 ng/dL) were inversely related to salt intake, whereas
      there were no changes in plasma norepinephrine. Although mean arterial pressure
      (19-22 mm Hg) and norepinephrine (20%-40%) were lower at all salt intakes during
      BA, neither the changes in pressure nor the absolute values for plasma renin
      activity or aldosterone in response to salt were different from control
      conditions. These findings demonstrate that suppression of sympathetic activity
      by BA lowers arterial pressure without increasing renin release and indicate that
      changes in sympathetic activity are not primary mediators of the effect of salt
      on renin secretion. Consequently, blood pressure lowering during BA is
      independent of salt intake. 

PMID- 24935943
TI  - Ambient air pollution and pregnancy-induced hypertensive disorders: a systematic
      review and meta-analysis.
AB  - Pregnancy-induced hypertensive disorders can lead to maternal and perinatal
      morbidity and mortality, but the cause of these conditions is not well
      understood. We have systematically reviewed and performed a meta-analysis of
      epidemiological studies investigating the association between exposure to ambient
      air pollution and pregnancy-induced hypertensive disorders including gestational
      hypertension and preeclampsia. We searched electronic databases for English
      language studies reporting associations between ambient air pollution and
      pregnancy-induced hypertensive disorders published between December 2009 and
      December 2013. Combined risk estimates were calculated using random-effect models
      for each exposure that had been examined in >=4 studies. Heterogeneity and
      publication bias were evaluated. A total of 17 articles evaluating the impact of
      nitrogen oxides (NO2, NOX), particulate matter (PM10, PM2.5), carbon monoxide
      (CO), ozone (O3), proximity to major roads, and traffic density met our inclusion
      criteria. Most studies reported that air pollution increased risk for pregnancy
      induced hypertensive disorders. There was significant heterogeneity in meta
      analysis, which included 16 studies reporting on gestational hypertension and
      preeclampsia as separate or combined outcomes; there was less heterogeneity in
      findings of the 10 studies reporting solely on preeclampsia. Meta-analyses showed
      increased risks of hypertensive disorders in pregnancy for all pollutants except
      CO. Random-effect meta-analysis combined odds ratio associated with a 5-MUg/m3
      increase in PM2.5 was 1.57 (95% confidence interval, 1.26-1.96) for combined
      pregnancy-induced hypertensive disorders and 1.31 (95%confidence interval, 1.14
      1.50) for preeclampsia [corrected]. Our results suggest that exposure to air
      pollution increases the risk of pregnancy-induced hypertensive disorders.

PMID- 24935942
TI  - Increased angiotensin II contraction of the uterine artery at early gestation in
      a transgenic model of hypertensive pregnancy is reduced by inhibition of
      endocannabinoid hydrolysis.
AB  - Increased vascular sensitivity to angiotensin II (Ang II) is a marker of a
      hypertensive human pregnancy. Recent evidence of interactions between the renin
      angiotensin system and the endocannabinoid system suggests that anandamide and 2
      arachidonoylglycerol may modulate Ang II contraction. We hypothesized that these
      interactions may contribute to the enhanced vascular responses in hypertensive
      pregnancy. We studied Ang II contraction in isolated uterine artery (UA) at early
      gestation in a rat model that mimics many features of preeclampsia, the
      transgenic human angiotensinogen*human renin (TgA), and control Sprague-Dawley
      rats. We determined the role of the cannabinoid receptor 1 by blockade with
      SR171416A, and the contribution of anandamide and 2-arachidonoylglycerol
      degradation to Ang II contraction by inhibiting their hydrolyzing enzyme fatty
      acid amide hydrolase (with URB597) or monoacylglycerol lipase (with JZL184),
      respectively. TgA UA showed increased maximal contraction and sensitivity to Ang
      II that was inhibited by indomethacin. Fatty acid amide hydrolase blockade
      decreased Ang IIMAX in Sprague-Dawley UA, and decreased both Ang IIMAX and
      sensitivity in TgA UA. Monoacylglycerol lipase blockade had no effect on Sprague
      Dawley UA and decreased Ang IIMAX and sensitivity in TgA UA. Blockade of the
      cannabinoid receptor 1 in TgA UA had no effect. Immunolocalization of fatty acid
      amide hydrolase and monoacylglycerol lipase showed a similar pattern between
      groups; fatty acid amide hydrolase predominantly localized in endothelium and
      monoacylglycerol lipase in smooth muscle cells. We demonstrated an increased Ang
      II contraction in TgA UA before initiation of the hypertensive phenotype.
      Anandamide and 2-arachidonoylglycerol reduced Ang II contraction in a cannabinoid
      receptor 1-independent manner. These renin-angiotensin system-endocannabinoid
      system interactions may contribute to the enhanced vascular reactivity in early
      stages of hypertensive pregnancy. 

PMID- 24935944
TI  - HV1 acts as a sodium sensor and promotes superoxide production in medullary thick
      ascending limb of Dahl salt-sensitive rats.
AB  - We previously characterized a H(+) transport pathway in medullary thick ascending
      limb nephron segments that when activated stimulated the production of superoxide
      by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity
      of this pathway was greater in Dahl salt-sensitive rats than salt-resistant
      (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The
      goal of this study was to determine the molecular identity of this pathway and
      its relationship to Na(+). We hypothesized that the voltage-gated proton channel,
      HV1, was the source of superoxide-stimulating H(+) currents. To test this
      hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat
      genetic background using zinc-finger nuclease gene targeting. HV1 could be
      detected in medullary thick limb from wild-type rats. Intracellular acidification
      using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide
      production in thick limb from wild-type but not HV1(-/-) rats (P<0.05) and more
      rapid recovery of intracellular pH in wild-type rats (DeltapHI 0.005 versus 0.002
      U/s, P=0.046, respectively). Superoxide production was enhanced by low
      intracellular sodium (<10 mmol/L) in both thick limb and peritoneal macrophages
      only when HV1 was present. When fed a high-salt diet, blood pressure, outer
      medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal
      staining) were significantly reduced in HV1(-/-) rats compared with wild-type
      Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick
      ascending limb and promotes superoxide production in this segment when
      intracellular Na(+) is low. HV1 contributes to the development of hypertension
      and renal disease in Dahl salt-sensitive rats. 

PMID- 24935945
TI  - Systolic and diastolic blood pressure, incident cardiovascular events, and death
      in elderly persons: the role of functional limitation in the Cardiovascular
      Health Study.
AB  - Whether limitation in the ability to perform activities of daily living (ADL) or
      gait speed can identify elders in whom the association of systolic and diastolic
      blood pressure (DBP) with cardiovascular events (CVDs) and death differs is
      unclear. We evaluated whether limitation in ADL or gait speed modifies the
      association of systolic blood pressure or DBP with incident CVD (n=2358) and
      death (n=3547) in the Cardiovascular Health Study. Mean age was 78+/-5 and 21%
      reported limitation in >=1 ADL. There were 778 CVD and 1289 deaths over 9 years.
      Among persons without and those with ADL limitation, systolic blood pressure was
      associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95%
      confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL
      modified the association of DBP with incident CVD. Among those without ADL
      limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for
      DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was
      inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR
      0.49 (0.25, 0.94) for DBP >80, compared with DBP <=65. Among people with ADL
      limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91),
      compared with a DBP of <=65. Associations did not vary by 15-feet walking speed.
      ADL can identify elders in whom diastolic hypotension is associated with higher
      cardiovascular risk and death. Functional status, rather than chronologic age
      alone, should inform design of hypertension trials in elders. 

PMID- 24935946
TI  - The physiological target for LeuRS translational quality control is norvaline.
AB  - The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA
      synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid
      selectivity is compromised, fidelity can be ensured by an inherent AARS editing
      activity that hydrolyses mischarged tRNAs. Here, we show that the editing
      activity of Escherichia coli leucyl-tRNA synthetase (EcLeuRS) is not required to
      prevent incorrect isoleucine incorporation. Rather, as shown by kinetic,
      structural and in vivo approaches, the prime biological function of LeuRS editing
      is to prevent mis-incorporation of the non-standard amino acid norvaline. This
      conclusion follows from a reassessment of the discriminatory power of LeuRS
      against isoleucine and the demonstration that a LeuRS editing-deficient E. coli
      strain grows normally in high concentrations of isoleucine but not under oxygen
      deprivation conditions when norvaline accumulates to substantial levels. Thus,
      AARS-based translational quality control is a key feature for bacterial adaptive
      response to oxygen deprivation. The non-essential role for editing under normal
      bacterial growth has important implications for the development of resistance to
      antimicrobial agents targeting the LeuRS editing site. 

PMID- 24935947
TI  - Seroepidemiological study of outdoor recreationists' exposure to spotted fever
      group Rickettsia in Western Australia.
AB  - Bushland activity has previously been linked to rickettsial exposure in eastern
      and central regions of Australia, whereas little is known about the risks in
      Western Australia. The isolation of Rickettsia gravesii sp. nov. from Amblyomma
      triguttatum ticks and anecdotal reports of low-grade illness among bush
      recreationists raised the possibility of rickettsial transmission in the State.
      This study investigated rickettsial seroprevalence and potential risk of exposure
      to the spotted fever group rickettsiae in rogainers. Our results showed that
      rogainers active in the bush had a significantly higher risk of seropositivity
      (immunofluorescence total antibody titer >= 128) for the spotted fever group
      Rickettsia (odds ratio [OR] = 14.02, 95% confidence interval [CI] = 1.38-142.07)
      compared with a reference population, the overall seroprevalence in the rogainer
      group being 23.1%. 

PMID- 24935948
TI  - Seroprevalence of Trypanosoma cruzi among mothers and children in rural Mayan
      communities and associated reproductive outcomes.
AB  - Our objective was to determine the seroprevalence of Trypanosoma cruzi infection
      among mothers and children in two rural Mayan communities in Yucatan, Mexico and
      examine sociodemographic characteristics and adverse reproductive outcomes
      associated with maternal infection. We performed household surveys in the
      communities of Sudzal and Teya. Mothers were interviewed, and blood samples were
      obtained to perform rapid tests and enzyme-linked immunosorbent assays (ELISAs).
      We surveyed 390 mothers and 685 children. The overall seroprevalence was 2.3%
      among mothers and 0.4% among children. In Sudzal, we found a seroprevalence of
      4.4% among mothers and 0.7% in children. In Teya, we found a seroprevalence of
      0.9% among mothers and 0.3% among children. Compared with uninfected mothers,
      seropositive mothers reported more stillbirths (relative risk = 4.7; 95%
      confidence interval = 2.1-10.4). T. cruzi infection is present in these
      communities, and infected children indicate active transmission. Seropositivity
      in mothers is associated with a history of adverse reproductive outcomes. 

PMID- 24935949
TI  - Reversibility of retinal microvascular changes in severe falciparum malaria.
AB  - Malarial retinopathy allows detailed study of central nervous system vascular
      pathology in living patients with severe malaria. An adult with cerebral malaria
      is described who had prominent retinal whitening with corresponding retinal
      microvascular obstruction, vessel dilatation, increased vascular tortuosity, and
      blood retinal barrier leakage with decreased visual acuity, all of which resolved
      on recovery. Additional study of these features and their potential role in
      elucidating the pathogenesis of cerebral malaria is warranted. 

PMID- 24935950
TI  - Detection of Bartonella quintana in African body and head lice.
AB  - Currently, the body louse is the only recognized vector of Bartonella quintana,
      an organism that causes trench fever. In this work, we investigated the
      prevalence of this bacterium in human lice in different African countries. We
      tested 616 head lice and 424 body lice from nine African countries using real
      time polymerase chain reaction targeting intergenic spacer region 2 and specific
      B. quintana genes. Overall, B. quintana DNA was found in 54% and 2% of body and
      head lice, respectively. Our results also show that there are more body lice
      positive for B. quintana in poor countries, which was determined by the gross
      domestic product, than in wealthy areas (228/403 versus 0/21, P < 0.001). A
      similar finding was obtained for head lice (8/226 versus 2/390, P = 0.007). Our
      findings suggest that head lice in Africa may be infected by B. quintana when
      patients live in poor economic conditions and are also exposed to body lice. 

PMID- 24935951
TI  - Trypanosoma cruzi infection in Mepraia gajardoi and Mepraia spinolai: the effect
      of feeding nymphs from the field.
AB  - We evaluated Trypanosoma cruzi infection rates by means of minicircle DNA-based
      polymerase chain reactions (PCRs) in 70 starved Mepraia gajardoi from northern
      Chile and 65 M. spinolai from central Chile after feeding. Immediately after
      collection in the field, 20% of M. gajardoi were found infected; after feeding,
      67% of the uninfected were infected. One group of M. spinolai seemed to be
      completely uninfected, but after the first and second feedings, 62% and 59% were
      positive, respectively. 

PMID- 24935953
TI  - High sensitivity and specificity of clinical microscopy in rural health
      facilities in western Kenya under an external quality assurance program.
AB  - Microscopic diagnosis of malaria is a well-established and inexpensive technique
      that has the potential to provide accurate diagnosis of malaria infection.
      However, it requires both training and experience. Although it is considered the
      gold standard in research settings, the sensitivity and specificity of routine
      microscopy for clinical care in the primary care setting has been reported to be
      unacceptably low. We established a monthly external quality assurance program to
      monitor the performance of clinical microscopy in 17 rural health centers in
      western Kenya. The average sensitivity over the 12-month period was 96% and the
      average specificity was 88%. We identified specific contextual factors that
      contributed to inadequate performance. Maintaining high-quality malaria diagnosis
      in high-volume, resource-constrained health facilities is possible. 

PMID- 24935952
TI  - Infection with Leishmania (Leishmania) infantum of 0 to 18-Month-old children
      living in a visceral leishmaniasis-endemic area in Brazil.
AB  - The diagnosis of Leishmania (Leishmania) infantum infection in children from
      birth may serve as a reference for the early identification of cases that would
      progress to classical visceral leishmaniasis (VL) in endemic areas. This study
      prospectively evaluated newborns of mothers living in the municipality of
      Paracatu, Minas Gerais, Brazil. The infants were followed up at 6-month intervals
      by clinical examination, serological tests (immunofluorescence [IIF] and enzyme
      linked immunosorbent assay with rK39 [ELISA-rK39]) and polymerase chain reaction
      (PCR) until they had completed 18 months of age. A total of 166 pregnant women
      were included to evaluate the possible transfer of antibodies or even congenital
      transmission. Twenty-two of the women tested positive by IIF, four by ELISA-rK39,
      and one by PCR. Three infants of the 25 women with some positive test results
      were also positive in the first test (one by IIF, one by ELISA-rK39, and the
      third by ELISA-rK39 and PCR). One hundred and sixty infants were included in the
      study; of these, 43 had at least one positive sample over time. However,
      agreement between tests was low. Follow-up of children with a positive result in
      the tests studied revealed no progression to classical disease within a period of
      18 months. In contrast, two children with negative IIF, PCR, and ELISA-rK39
      results developed classical VL at 9 and 12 months of age. In conclusion, a
      positive test result was variable and sometimes temporary and agreement between
      tests was low. Therefore, the early diagnosis of Leishmania infection was not
      associated with the early identification of cases that would progress to
      classical VL in the endemic area studied. 

PMID- 24935954
TI  - Population ecology of hantavirus rodent hosts in southern Brazil.
AB  - In this study we analyze population dynamics of hantavirus rodent hosts and
      prevalence of infection over a 2-year period in Southern Brazil, a region with a
      high incidence of hantavirus pulmonary syndrome. The 14 small mammal species
      captured were composed of 10 rodents and four marsupials, the six most abundant
      species being Akodon serrensis, Oxymycterus judex, Akodon montensis, Akodon
      paranaensis, Oligoryzomys nigripes, and Thaptomys nigrita. These species
      displayed a similar pattern with increasing population sizes in fall/winter
      caused by recruitment and both, increase in reproductive activity and higher
      hantavirus prevalence in spring/summer. Specific associations between A.
      montensis/Jabora Virus (JABV) and O. nigripes/Juquitiba-like Virus (JUQV-like)
      and spillover infections between A. paranaensis/JABV, A. serrensis/JABV, and A.
      paranaensis/JUQV-like were observed. Spillover infection in secondary hosts seems
      to play an important role in maintaining JABV and JUQV-like in the hantavirus
      sylvatic cycle mainly during periods of low prevalence in primary hosts. 

PMID- 24935955
TI  - Decreased HIV type 1 transcription in CCR5-Delta32 heterozygotes during
      suppressive antiretroviral therapy.
AB  - Individuals who are heterozygous for the CCR5-Delta32 mutation provide a natural
      model to examine the effects of reduced CCR5 expression on human immunodeficiency
      virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Delta32
      heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral
      therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional
      ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular
      DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Delta32
      heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5
      surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that
      curative strategies should further explore manipulation of CCR5.

PMID- 24935956
TI  - Development of microRNA therapeutics is coming of age.
AB  - MicroRNAs (miRNAs) play key regulatory roles in diverse biological processes and
      are frequently dysregulated in human diseases. Thus, miRNAs have emerged as a
      class of promising targets for therapeutic intervention. Here, we describe the
      current strategies for therapeutic modulation of miRNAs and provide an update on
      the development of miRNA-based therapeutics for the treatment of cancer,
      cardiovascular disease and hepatitis C virus (HCV) infection. 

PMID- 24935957
TI  - Characterization of lung inflammation and its impact on macrophage function in
      aging.
AB  - Systemic inflammation that occurs with increasing age (inflammaging) is thought
      to contribute to the increased susceptibility of the elderly to several disease
      states. The elderly are at significant risk for developing pulmonary disorders
      and infectious diseases, but the contribution of inflammation in the pulmonary
      environment has received little attention. In this study, we demonstrate that the
      lungs of old mice have elevated levels of proinflammatory cytokines and a
      resident population of highly activated pulmonary macrophages that are refractory
      to further activation by IFN-gamma. The impact of this inflammatory state on
      macrophage function was determined in vitro in response to infection with M.tb.
      Macrophages from the lungs of old mice secreted more proinflammatory cytokines in
      response to M.tb infection than similar cells from young mice and also
      demonstrated enhanced M.tb uptake and P-L fusion. Supplementation of mouse chow
      with the NSAID ibuprofen led to a reversal of lung and macrophage inflammatory
      signatures. These data indicate that the pulmonary environment becomes
      inflammatory with increasing age and that this inflammatory environment can be
      reversed with ibuprofen. 

PMID- 24935959
TI  - A chasm of misunderstanding: The widening gap between public perception and
      scientific consensus.

PMID- 24935958
TI  - An essential role of interleukin-17 receptor signaling in the development of
      autoimmune glomerulonephritis.
AB  - In recent years, proinflammatory cytokines in the nephritic kidney appear to
      contribute to the pathogenesis of AGN. The complex inflammatory cytokine network
      that drives renal pathology is poorly understood. IL-17, the signature cytokine
      of Th17 cells, which promotes autoimmune pathology in a variety of settings, is
      beginning to be identified in acute and chronic kidney diseases as well. However,
      the role of IL-17-mediated renal damage in the nephritic kidney has not been
      elucidated. Here, with the use of a murine model of experimental AGN, we showed
      that IL-17RA signaling is critical for the development of renal pathology.
      Despite normal systemic autoantibody response and glomerular immune-complex
      deposition, IL-17RA(-/-) mice exhibit a diminished influx of inflammatory cells
      and kidney-specific expression of IL-17 target genes correlating with disease
      resistance in AGN. IL-17 enhanced the production of proinflammatory cytokines and
      chemokines from tECs. Finally, we were able to show that neutralization of IL-17A
      ameliorated renal pathology in WT mice following AGN. These results clearly
      demonstrated that IL-17RA signaling significantly contributes to renal tissue
      injury in experimental AGN and suggest that blocking IL-17RA may be a promising
      therapeutic strategy for the treatment of proliferative and crescentic
      glomerulonephritis. 

PMID- 24935960
TI  - Do child's psychosocial functioning, and parent and family characteristics
      predict early alcohol use? The TRAILS Study.
AB  - BACKGROUND: Given the negative consequences of early alcohol use for health and
      social functioning, it is essential to detect children at risk of early drinking.
      The aim of this study is to determine predictors of early alcohol use that can
      easily be detected in Preventive Child Healthcare (PCH). METHODS: We obtained
      data from the first two waves on 1261 Dutch adolescents who participated in
      TRAILS (TRacking Adolescents' Individual Lives Survey) at ages 10-14 years and
      from the PCH records regarding ages 4-10 years. Early adolescence alcohol use
      (age 10-14 years) was defined as alcohol use at least once at ages 10-12 years
      (wave 1) and at least once in the previous 4 weeks at ages 12-14 years (wave 2).
      Predictors of early alcohol use concerned parent and teacher reports at wave 1
      and PCH registrations, regarding the child's psychosocial functioning, and
      parental and socio-demographic characteristics. RESULTS: A total of 17.2% of the
      adolescents reported early alcohol use. Predictors of early alcohol use were
      teacher-reported aggressive behaviour [odds ratios (OR); 95% confidence interval
      (CI): 1.86; 1.11-3.11], being a boy (OR 1.80, 95%-CI 1.31-2.56), being a non
      immigrant (OR 2.31, 95%CI 1.05-5.09), and low and middle educational level of the
      father (OR 1.71, 95%CI 1.12-2.62 and OR 1.77, 95%CI 1.16-2.70, respectively),
      mutually adjusted. CONCLUSION: A limited set of factors was predictive for early
      alcohol use. Use of this set may improve the detection of early adolescence
      alcohol use in PCH.

PMID- 24935961
TI  - Transgenic expression of dominant-active IDOL in liver causes diet-induced
      hypercholesterolemia and atherosclerosis in mice.
AB  - RATIONALE: The E3 ubiquitin ligase inducible degrader of the low-density
      lipoprotein receptor (IDOL) triggers lysosomal degradation of the low-density
      lipoprotein receptor. The tissue-specific effects of the IDOL pathway on plasma
      cholesterol and atherosclerosis have not been examined. OBJECTIVE: Given that the
      liver is the primary determinant of plasma cholesterol levels, we sought to
      examine the consequence of effect of chronic liver-specific expression of a
      dominant-active form of IDOL in mice. METHODS AND RESULTS: We expressed a
      degradation-resistant, dominant-active form of IDOL (super IDOL [sIDOL]) in
      C57Bl/6J mice from the liver-specific albumin promoter (L-sIDOL transgenics). L
      sIDOL mice were fed a Western diet for 20 or 30 weeks and then analyzed for
      plasma lipid levels and atherosclerotic lesion formation. L-sIDOL mice showed
      dramatic reductions in hepatic low-density lipoprotein receptor protein and
      increased plasma low-density lipoprotein cholesterol levels on both chow and
      Western diets. Moreover, L-sIDOL mice developed marked atherosclerotic lesions
      when fed a Western diet. Lesion formation in L-sIDOL mice was more robust than in
      apolipoprotein E*3 Leiden mice and did not require the addition of cholate to the
      diet. Western diet-fed L-sIDOL mice had elevated expression of liver X receptor
      target genes and proinflammatory genes in their aortas. CONCLUSIONS: Liver
      specific expression of dominant-active IDOL is associated with
      hypercholesterolemia and a marked elevation in atherosclerotic lesions. Our
      results show that increased activity of the IDOL pathway in the liver can
      override other low-density lipoprotein receptor regulatory pathways leading to
      cardiovascular disease. L-sIDOL mice are a robust, dominantly inherited, diet
      inducible model for the study of atherosclerosis.

PMID- 24935962
TI  - Embryonic stem cell-derived cardiac myocytes are not ready for human trials.

PMID- 24935963
TI  - High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma
      families.
AB  - BACKGROUND: Germline mutations in the tumour suppressor gene CDKN2A occur in 5
      20% of familial melanoma cases. A single founder mutation, p.Arg112dup, accounts
      for the majority of CDKN2A mutations in Swedish carriers. In a national program,
      carriers of p.Arg112dup mutation have been identified. The aim of this study was
      to assess cancer risks in p.Arg112dup carriers and their first degree relatives
      (FDRs) and second degree relatives (SDRs). METHODS: In this prospective cohort
      study, cancer diagnoses in carriers (n=120), non-carriers (n=111), carriers' FDRs
      (n=275) and SDRs (n=321) and controls (n=3976) were obtained from the Swedish
      Cancer Registry. Relative risks (RRs) for cancers were calculated (number of
      cancers/person years). Two-sided 95% CIs were calculated for all RRs. RESULTS: In
      carriers prospective RR for non-melanoma cancers was 5.0 (95% CI 3.7 to 7.3), for
      pancreatic cancer 43.8 (95% CI 13.8 to 139.0), for cancers in upper digestive
      tissues 17.1 (95% CI 6.3 to 46.5), and in respiratory tissues 15.6 (5.4 to 46.0).
      In FDRs and SDRs RRs were significantly elevated for cancers in pancreas,
      respiratory and upper digestive tissues. In ever-smoking carriers compared with
      never-smoking carriers, the odds ratio (OR) of cancers in pancreas, respiratory
      or upper digestive tissues was 9.3 (95% CI 1.9 to 44.7). CONCLUSIONS: CDKN2A
      p.Arg112dup mutation carriers from melanoma-prone families and their FDRs and
      SDRs have elevated risk for pancreatic, lung, head and neck and gastro
      oesophageal carcinomas. These cancers were mainly seen in ever-smoking carriers.
      Germline CDKN2A mutations may confer an increased sensitivity to carcinogens in
      tobacco smoke. CDKN2A mutation carriers should be counselled to abstain from
      smoking.

PMID- 24935968
TI  - MAPKAP kinase 3 suppresses Ifng gene expression and attenuates NK cell
      cytotoxicity and Th1 CD4 T-cell development upon influenza A virus infection.
AB  - MK2 and MK3 are downstream targets of p38 and ERK1/2. They control the mRNA
      stability of several inflammatory cytokines, including TNF-alpha and IL-10.
      Whereas MK2 is expressed ubiquitously, the expression of MK3 is restricted to
      muscle, liver, and heart tissues and T and NK cells. Using Mk-deficient and wild
      type (WT) mice, we demonstrated an inhibitory effect of MK3, but not of MK2, on
      interferon (IFN)-gamma expression in T and NK lymphocytes. The results provided
      evidence that the inhibitory effect of MK3 is based on negative feedback
      phosphorylation of p38 and ERK1/2, which causes decreased binding of Stat4 to the
      IFN-gamma promoter and reduced expression of IFN-gamma mRNA and protein.
      Consequently, all Mk3(-/-) mice challenged with the Th1-inducing influenza A
      virus (IAV) survived the WT LD50 virus dose. The reduced disease severity in the
      Mk3(-/-) mice was accompanied by a >10-fold reduction in viral lung titer and an
      increase in the number of activated NK cells and enhanced Th1 activation of CD4 T
      cells. Thus, our data describe the protein kinase MK3 as a novel regulator of the
      innate and adaptive immune responses.-Kother, K., Nordhoff, C., Masemann, D.,
      Varga, G., Bream, J. H., Gaestel, M., Wixler, V., Ludwig, S. MAPKAP kinase 3
      suppresses Ifng gene expression and attenuates NK cell cytotoxicity and Th1 CD4 T
      cell development upon influenza A virus infection. 

PMID- 24935969
TI  - Television viewing and time spent sedentary in relation to cancer risk: a meta
      analysis.
AB  - BACKGROUND: Sedentary behavior is emerging as an independent risk factor for
      chronic disease and mortality. However, the evidence relating television (TV)
      viewing and other sedentary behaviors to cancer risk has not been quantitatively
      summarized. METHODS: We performed a comprehensive electronic literature search in
      Cochrane, EMBASE, Medline, and SciSearch databases through February 2014 for
      published articles investigating sedentary behavior in relation to cancer
      incidence. Because randomized controlled trials are difficult to perform on this
      topic, we focused on observational studies that met uniform inclusion criteria.
      Data were extracted independently by both authors and summarized using random
      effects meta-analysis and meta-regression. All statistical tests were two-sided.
      RESULTS: Data from 43 observational studies including a total of 68936 cancer
      cases were analyzed. Comparing the highest vs lowest levels of sedentary time,
      the relative risks (RRs) for colon cancer were 1.54 (95% confidence interval [CI]
      = 1.19 to 1.98) for TV viewing time, 1.24 (95% CI = 1.09 to 1.41) for
      occupational sitting time, and 1.24 (95% CI = 1.03 to 1.50) for total sitting
      time. For endometrial cancer, the relative risks were 1.66 (95% CI = 1.21 to
      2.28) for TV viewing time and 1.32 (95% CI = 1.08 to 1.61) for total sitting
      time. A positive association with overall sedentary behavior was also noted for
      lung cancer (RR = 1.21; 95% CI = 1.03 to 1.43). Sedentary behavior was unrelated
      to cancers of the breast, rectum, ovaries, prostate, stomach, esophagus, testes,
      renal cell, and non-Hodgkin lymphoma. CONCLUSIONS: Prolonged TV viewing and time
      spent in other sedentary pursuits is associated with increased risks of certain
      types of cancer.

PMID- 24935970
TI  - An active lifestyle for cancer prevention.

PMID- 24935971
TI  - Different types of secondary information in the genetic code.
AB  - Whole-genome and functional analyses suggest a wealth of secondary or auxiliary
      genetic information (AGI) within the redundancy component of the genetic code.
      Although there are multiple aspects of biased codon use, we focus on two types of
      auxiliary information: codon-specific translational pauses that can be used by
      particular proteins toward their unique folding and biased codon patterns shared
      by groups of functionally related mRNAs with coordinate regulation. AGI is
      important to genetics in general and to human disease; here, we consider
      influences of its three major components, biased codon use itself, variations in
      the tRNAome, and anticodon modifications that distinguish synonymous decoding.
      AGI is plastic and can be used by different species to different extents, with
      tissue-specificity and in stress responses. Because AGI is species-specific, it
      is important to consider codon-sensitive experiments when using heterologous
      systems; for this we focus on the tRNA anticodon loop modification enzyme,
      CDKAL1, and its link to type 2 diabetes. Newly uncovered tRNAome variability
      among humans suggests roles in penetrance and as a genetic modifier and disease
      modifier. Development of experimental and bioinformatics methods are needed to
      uncover additional means of auxiliary genetic information. 

PMID- 24935972
TI  - Endotoxin-induced endothelial fibrosis is dependent on expression of transforming
      growth factors beta1 and beta2.
AB  - During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate
      in the bloodstream and interact with endothelial cells (ECs), inducing
      dysfunction of the ECs. We previously reported that endotoxins induce the
      conversion of ECs into activated fibroblasts. Through endotoxin-induced
      endothelial fibrosis, ECs change their morphology and their protein expression
      pattern, thereby suppressing endothelial markers and upregulating fibrotic
      proteins. The most commonly used fibrotic inducers are transforming growth factor
      beta1 (TGF-beta1) and TGF-beta2. However, whether TGF-beta1 and TGF-beta2
      participate in endotoxin-induced endothelial fibrosis remains unknown. We have
      shown that the endotoxin-induced endothelial fibrosis process is dependent on the
      TGF-beta receptor, ALK5, and the activation of Smad3, a protein that is activated
      by ALK5 activation, thus suggesting that endotoxin elicits TGF-beta production to
      mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the
      dependence of endotoxin-induced endothelial fibrosis on the expression of TGF
      beta1 and TGF-beta2. Endotoxin-treated ECs induced the expression and secretion
      of TGF-beta1 and TGF-beta2. TGF-beta1 and TGF-beta2 downregulation inhibited the
      endotoxin-induced changes in the endothelial marker VE-cadherin and in the
      fibrotic proteins alpha-SMA and fibronectin. Thus, endotoxin induces the
      production of TGF-beta1 and TGF-beta2 as a mechanism to promote endotoxin-induced
      endothelial fibrosis. To the best of our knowledge, this is the first report
      showing that endotoxin induces endothelial fibrosis via TGF-beta secretion, which
      represents an emerging source of vascular dysfunction. These findings contribute
      to understanding the molecular mechanism of endotoxin-induced endothelial
      fibrosis, which could be useful in the treatment of inflammatory diseases. 

PMID- 24935973
TI  - Identification and characterization of outer membrane vesicle-associated proteins
      in Salmonella enterica serovar Typhimurium.
AB  - Salmonella enterica serovar Typhimurium is a primary cause of enteric diseases
      and has acquired a variety of virulence factors during its evolution into a
      pathogen. Secreted virulence factors interact with commensal flora and host cells
      and enable Salmonella to survive and thrive in hostile environments. Outer
      membrane vesicles (OMVs) released from many Gram-negative bacteria function as a
      mechanism for the secretion of complex mixtures, including virulence factors. We
      performed a proteomic analysis of OMVs that were isolated under standard
      laboratory and acidic minimal medium conditions and identified 14 OMV-associated
      proteins that were observed in the OMV fraction isolated only under the acidic
      minimal medium conditions, which reproduced the nutrient-deficient intracellular
      milieu. The inferred roles of these 14 proteins were diverse, including
      transporter, enzyme, and transcriptional regulator. The absence of these proteins
      influenced Salmonella survival inside murine macrophages. Eleven of these
      proteins were predicted to possess secretion signal sequences at their N termini,
      and three (HupA, GlnH, and PhoN) of the proteins were found to be translocated
      into the cytoplasm of host cells. The comparative proteomic profiling of OMVs
      performed in this study revealed different protein compositions in the OMVs
      isolated under the two different conditions, which indicates that the OMV cargo
      depends on the growth conditions and provides a deeper insight into how
      Salmonella utilizes OMVs to adapt to environmental changes. 

PMID- 24935974
TI  - Parasite-derived neurotrophic factor/trans-sialidase of Trypanosoma cruzi links
      neurotrophic signaling to cardiac innate immune response.
AB  - The Chagas' disease parasite Trypanosoma cruzi elicits a potent inflammatory
      response in acutely infected hearts that keeps parasitism in check and triggers
      cardiac abnormalities. A most-studied mechanism underlying innate immunity in T.
      cruzi infection is Toll-like receptor (TLR) activation by lipids and other
      parasite molecules. However, yet-to-be-identified pathways should exist. Here, we
      show that T. cruzi strongly upregulates monocyte chemoattractant protein 1 (MCP
      1)/CCL2 and fractalkine (FKN)/CX3CL1 in cellular and mouse models of heart
      infection. Mechanistically, upregulation of MCP-1 and FKN stems from the
      interaction of parasite-derived neurotrophic factor (PDNF)/trans-sialidase with
      neurotrophic receptors TrkA and TrkC, as assessed by pharmacological inhibition,
      neutralizing antibodies, and gene silencing studies. Administration of a single
      dose of intravenous PDNF to naive mice results in a dose-dependent increase in
      MCP-1 and FKN in the heart and liver with pulse-like kinetics that peak at 3 h
      postinjection. Intravenous PDNF also augments MCP-1 and FKN in TLR signaling
      deficient MyD88-knockout mice, underscoring the MyD88-independent action of PDNF.
      Although single PDNF injections do not increase MCP-1 and FKN receptors, multiple
      PDNF injections at short intervals up the levels of receptor transcripts in the
      heart and liver, suggesting that sustained PDNF triggers cell recruitment at
      infection sites. Thus, given that MCP-1 and FKN are chemokines essential to the
      recruitment of immune cells to combat inflammation triggers and to enhance tissue
      repair, our findings uncover a new mechanism in innate immunity against T. cruzi
      infection mediated by Trk signaling akin to an endogenous inflammatory and
      fibrotic pathway resulting from cardiomyocyte-TrkA recognition by matricellular
      connective tissue growth factor (CTGF/CCN2). 

PMID- 24935975
TI  - Expression of regulatory T cells in jejunum, colon, and cervical and mesenteric
      lymph nodes of dogs naturally infected with Leishmania infantum.
AB  - Using flow cytometry, we evaluated the frequencies of CD4(+) and CD8(+) T cells
      and Foxp3(+) regulatory T cells (Tregs) in mononuclear cells in the jejunum,
      colon, and cervical and mesenteric lymph nodes of dogs naturally infected with
      Leishmania infantum and in uninfected controls. All infected dogs showed chronic
      lymphadenitis and enteritis. Despite persistent parasite loads, no erosion or
      ulcers were evident in the epithelial mucosa. The colon harbored more parasites
      than the jejunum. Frequencies of total CD4(+), total Foxp3, and CD4(+) Foxp3(+)
      cells were higher in the jejunum than in the colon. Despite negative enzyme
      linked immunosorbent assay (ELISA) serum results for cytokines, levels of
      interleukin-10 (IL-10), gamma interferon (IFN-gamma), transforming growth factor
      beta (TGF-beta), and tumor necrosis factor alpha (TNF-alpha) were higher in the
      jejunum than in the colon for infected dogs. However, IL-4 levels were higher in
      the colon than in the jejunum for infected dogs. There was no observed
      correlation between clinical signs and histopathological changes or immunological
      and parasitological findings in the gastrointestinal tract (GIT) of canines with
      visceral leishmaniasis. However, distinct segments of the GIT presented different
      immunological and parasitological responses. The jejunum showed a lower parasite
      load, with increased frequencies and expression of CD4, Foxp3, and CD8 receptors
      and IL-10, TGF-beta, IFN-gamma, and TNF-alpha cytokines. The colon showed a
      higher parasite load, with increasing expression of IL-4. Leishmania infantum
      infection increased expression of CD4, Foxp3, IL-10, TGF-beta, IFN-gamma, and TNF
      alpha and reduced CD8 and IL-4 expression in both the jejunum and the colon. 

PMID- 24935976
TI  - Distinct regions of NLRP1B are required to respond to anthrax lethal toxin and
      metabolic inhibition.
AB  - Pattern recognition receptors monitor for signs of infection or cellular
      dysfunction and respond to these events by initiating an immune response. NLRP1B
      is a receptor that upon activation recruits multiple copies of procaspase-1,
      which promotes cytokine processing and a proinflammatory form of cell death
      termed pyroptosis. NLRP1B detects anthrax lethal toxin when the toxin cleaves an
      amino-terminal fragment from the protein. In addition, NLRP1B is activated when
      cells are deprived of glucose or treated with metabolic inhibitors, but the
      mechanism by which the resulting reduction in cytosolic ATP is sensed by NLRP1B
      is unknown. Here, we addressed whether these two activating signals of NLRP1B
      converge on a common sensing system. We show that an NLRP1B mutant lacking the
      amino-terminal region exhibits some spontaneous activity and fails to be further
      activated by lethal toxin. This mutant was still activated in cells depleted of
      ATP, however, indicating that the amino-terminal region is not the sole sensing
      domain of NLRP1B. Mutagenesis of the leucine-rich repeat domain of NLRP1B
      provided evidence that this domain is involved in autoinhibition of the receptor,
      but none of the mutants tested was specifically defective at sensing activating
      signals. Comparison of two alleles of NLRP1B that differed in their response to
      metabolic inhibitors, but not to lethal toxin, led to the finding that a repeated
      sequence in the function to find domain (FIIND) that arose from exon duplication
      facilitated detection of ATP depletion. These results suggest that distinct
      regions of NLRP1B detect activating signals. 

PMID- 24935977
TI  - Elongation factor P and modifying enzyme PoxA are necessary for virulence of
      Shigella flexneri.
AB  - Elongation factor P (EF-P) is a universally conserved bacterial translation
      factor. In many bacteria, EF-P is posttranslationally modified by PoxA, which
      covalently attaches a beta-lysine to a conserved lysine residue of EF-P. Here we
      show that both EF-P and PoxA are necessary for virulence of the human diarrheal
      pathogen Shigella flexneri. Loss of either EF-P or PoxA leads to an impaired
      ability of S. flexneri to invade epithelial cells and form plaques in an
      epithelial cell monolayer. Proteomic analysis of efp and poxA deletion mutants
      revealed decreased levels of several virulence effector proteins, including IpaA,
      -B, and -C and IcsA. Additionally, mRNA levels of virB and virF, which encode
      master virulence regulators, were decreased in the efp mutant. The reduction in
      virF transcription was at least partially due to decreased levels of CpxA, which
      activates virF through the response regulator CpxR. The role of CpxAR in reduced
      synthesis of VirF and its downstream effectors was indicated by restoration of
      invasion when a mutation resulting in constitutively activated CpxR was
      introduced into the efp mutant. Thus, modified EF-P is required for appropriate
      synthesis of proteins involved in the virulence of this bacterial pathogen. 

PMID- 24935978
TI  - Identification of mechanisms for attenuation of the FSC043 mutant of Francisella
      tularensis SCHU S4.
AB  - Previously, we identified a spontaneous, essentially avirulent mutant, FSC043, of
      the highly virulent strain SCHU S4 of Francisella tularensis subsp. tularensis.
      We have now characterized the phenotype of the mutant and the mechanisms of its
      attenuation in more detail. Genetic and proteomic analyses revealed that the pdpE
      gene and most of the pdpC gene were very markedly downregulated and, as
      previously demonstrated, that the strain expressed partially deleted and fused
      fupA and fupB genes. FSC043 showed minimal intracellular replication and induced
      no cell cytotoxicity. The mutant showed delayed phagosomal escape; at 18 h,
      colocalization with LAMP-1 was 80%, indicating phagosomal localization, whereas
      the corresponding percentages for SCHU S4 and the DeltafupA mutant were <10%.
      However, a small subset of the FSC043-infected cells contained up to 100 bacteria
      with LAMP-1 colocalization of around 30%. The unusual intracellular phenotype was
      similar to that of the DeltapdpC and DeltapdpC DeltapdpE mutants. Complementation
      of FSC043 with the intact fupA and fupB genes did not affect the phenotype,
      whereas complementation with the pdpC and pdpE genes restored intracellular
      replication and led to marked virulence. Even higher virulence was observed after
      complementation with both double-gene constructs. After immunization with the
      FSC043 strain, moderate protection against respiratory challenge with the SCHU S4
      strain was observed. In summary, FSC043 showed a highly unusual intracellular
      phenotype, and based on our findings, we hypothesize that the mutation in the
      pdpC gene makes an essential contribution to the phenotype. 

PMID- 24935979
TI  - Contribution of the highly conserved EaeH surface protein to enterotoxigenic
      Escherichia coli pathogenesis.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes
      of diarrheal illness worldwide. These pathogens disproportionately afflict
      children in developing countries, where they cause substantial morbidity and are
      responsible for hundreds of thousands of deaths each year. Although these
      organisms are important targets for enteric vaccines, most development efforts to
      date have centered on a subset of plasmid-encoded fimbrial adhesins known as
      colonization factors and heat-labile toxin (LT). Emerging data suggest that ETEC
      undergoes considerable changes in its surface architecture, sequentially
      deploying a number of putative adhesins during its interactions with the host. We
      demonstrate here that one putative highly conserved, chromosomally encoded
      adhesin, EaeH, engages the surfaces of intestinal epithelial cells and
      contributes to bacterial adhesion, LT delivery, and colonization of the small
      intestine. 

PMID- 24935981
TI  - RS1 satellite phage promotes diversity of toxigenic Vibrio cholerae by driving
      CTX prophage loss and elimination of lysogenic immunity.
AB  - In El Tor biotype strains of toxigenic Vibrio cholerae, the CTXphi prophage often
      resides adjacent to a chromosomally integrated satellite phage genome, RS1, which
      produces RS1phi particles by using CTX prophage-encoded morphogenesis proteins.
      RS1 encodes RstC, an antirepressor against the CTXphi repressor RstR, which
      cooperates with the host-encoded LexA protein to maintain CTXphi lysogeny. We
      found that superinfection of toxigenic El Tor strains with RS1phi, followed by
      inoculation of the transductants into the adult rabbit intestine, caused
      elimination of the resident CTX prophage-producing nontoxigenic derivatives at a
      high frequency. Further studies using recA deletion mutants and a cloned rstC
      gene showed that the excision event was recA dependent and that introduction of
      additional copies of the cloned rstC gene instead of infection with RS1phi was
      sufficient to enhance CTXphi elimination. Our data suggest that once it is
      excised from the chromosome, the elimination of CTX prophage from host cells is
      driven by the inability to reestablish CTXphi lysogeny while RstC is
      overexpressed. However, with eventual loss of the additional copies of rstC, the
      nontoxigenic derivatives can act as precursors of new toxigenic strains by
      acquiring the CTX prophage either through reinfection with CTXphi or by chitin
      induced transformation. These results provide new insights into the role of
      RS1phi in V. cholerae evolution and the emergence of highly pathogenic clones,
      such as the variant strains associated with recent devastating epidemics of
      cholera in Asia, sub-Saharan Africa, and Haiti. 

PMID- 24935980
TI  - A conserved PapB family member, TosR, regulates expression of the uropathogenic
      Escherichia coli RTX nonfimbrial adhesin TosA while conserved LuxR family members
      TosE and TosF suppress motility.
AB  - A heterogeneous subset of extraintestinal pathogenic Escherichia coli (ExPEC)
      strains, referred to as uropathogenic E. coli (UPEC), causes most uncomplicated
      urinary tract infections. However, no core set of virulence factors exists among
      UPEC strains. Instead, the focus of the analysis of urovirulence has shifted to
      studying broad classes of virulence factors and the interactions between them.
      For example, the RTX nonfimbrial adhesin TosA mediates adherence to host cells
      derived from the upper urinary tract. The associated tos operon is well expressed
      in vivo but poorly expressed in vitro and encodes TosCBD, a predicted type 1
      secretion system. TosR and TosEF are PapB and LuxR family transcription factors,
      respectively; however, no role has been assigned to these potential regulators.
      Thus, the focus of this study was to determine how TosR and TosEF regulate tosA
      and affect the reciprocal expression of adhesins and flagella. Among a collection
      of sequenced UPEC strains, 32% (101/317) were found to encode TosA, and nearly
      all strains (91% [92/101]) simultaneously carried the putative regulatory genes.
      Deletion of tosR alleviates tosA repression. The tos promoter was localized
      upstream of tosR using transcriptional fusions of putative promoter regions with
      lacZ. TosR binds to this region, affecting a gel shift. A 100-bp fragment 220 to
      319 bp upstream of tosR inhibits binding, suggesting localization of the TosR
      binding site. TosEF, on the other hand, downmodulate motility when overexpressed
      by preventing the expression of fliC, encoding flagellin. Deletion of tosEF
      increased motility. Thus, we present an additional example of the reciprocal
      control of adherence and motility. 

PMID- 24935982
TI  - Alternative sigma factor RpoE is important for Vibrio parahaemolyticus cell
      envelope stress response and intestinal colonization.
AB  - Vibrio parahaemolyticus is a halophile that inhabits brackish waters and a wide
      range of hosts, including crustaceans, fish, mollusks, and humans. In humans, it
      is the leading cause of bacterial seafood-borne gastroenteritis. The focus of
      this work was to determine the role of alternative sigma factors in the stress
      response of V. parahaemolyticus RIMD2210633, an O3:K6 pandemic isolate.
      Bioinformatics identified five putative extracytoplasmic function (ECF) family of
      alternative sigma factors: VP0055, VP2210, VP2358, VP2578, and VPA1690. ECF
      factors typically respond to cell wall/cell envelope stress, iron levels, and the
      oxidation state of the cell. We have demonstrated here that one such sigma
      factor, VP2578, a homologue of RpoE from Escherichia coli, is important for
      survival under a number of cell envelope stress conditions and in
      gastrointestinal colonization of a streptomycin-treated adult mouse. In this
      study, we determined that an rpoE deletion mutant strain BHM2578 compared to the
      wild type (WT) was significantly more sensitive to polymyxin B, ethanol, and high
      temperature stresses. We demonstrated that in in vivo competition assays between
      the rpoE mutant and the WT marked with the beta-galactosidase gene lacZ
      (WBWlacZ), the mutant strain was defective in colonization compared to the WT. In
      contrast, deletion of the rpoS stress response regulator did not affect in vivo
      survival. In addition, we examined the role of the outer membrane protein, OmpU,
      which in V. cholerae is proposed to be the sole activator of RpoE. We found that
      an ompU deletion mutant was sensitive to bile salt stress but resistant to
      polymyxin B stress, indicating OmpU is not essential for the cell envelope stress
      responses or RpoE function. Overall, these data demonstrate that RpoE is a key
      cell envelope stress response regulator and, similar to E. coli, RpoE may have
      several factors that stimulate its function. 

PMID- 24935983
TI  - Somatic symptom count scores do not identify patients with symptoms unexplained
      by disease: a prospective cohort study of neurology outpatients.
AB  - OBJECTIVE: Somatic symptoms unexplained by disease are common in all medical
      settings. The process of identifying such patients requires a clinical assessment
      often supported by clinical tests. Such assessments are time-consuming and
      expensive. Consequently the observation that such patients tend to report a
      greater number of symptom has led to the use of self-rated somatic symptom counts
      as a simpler and cheaper diagnostic aid and proxy measure for epidemiological
      surveys. However, despite their increasing popularity there is little evidence to
      support their validity. METHODS: We tested the score on a commonly used self
      rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus
      enhanced iterations including an additional 10 items on specific neurological
      symptoms and an additional 5 items on mental state) for diagnostic sensitivity
      and specificity against a medical assessment (with 18 months follow-up) in a
      prospective cohort study of 3781 newly attending patients at neurology clinics in
      Scotland, UK. RESULTS: We found 1144/3781 new outpatients had symptoms that were
      unexplained by disease. The patients with symptoms unexplained by disease
      reported higher symptoms count scores (PHQ 15: 5.6 (95% CI 5.4 to 5.8) vs 4.2
      (4.1 to 4.4) p<0.0001). However, the PHQ15 performed little better than chance in
      its ability to identify patients with symptoms unexplained by disease. The
      findings with the enhanced scales were similar. CONCLUSIONS: Self-rated symptom
      count scores should not be used to identify patients with symptoms unexplained by
      disease.

PMID- 24935984
TI  - Serum neurofilament light chain is a biomarker of human spinal cord injury
      severity and outcome.
AB  - BACKGROUND: Neurofilaments (Nf) are major structural proteins that occur
      exclusively in neurons. In spinal cord injury (SCI), the severity of disease is
      quantified by clinical measures that have limited sensitivity and reliability,
      and no blood-based biomarker has been established to further stratify the degree
      of injury. We aimed to examine a serum-based NfL immunoassay as predictor of the
      clinical outcome in SCI. METHODS: Longitudinal measurement of serum NfL was
      performed in patients with central cord syndrome (CCS, n=4), motor-incomplete SCI
      (iSCI, n=10), motor-complete SCI (cSCI, n=13) and healthy controls (HC, n=67),
      and correlated with clinical severity, neurological outcome, and neuroprotective
      effect of the drug minocycline. RESULTS: Baseline NfL levels were higher in iSCI
      (21 pg/mL) and cSCI (70 pg/mL) than in HC (5 pg/mL, p=0.006 and p<0.001) and CCS
      (6 pg/mL, p=0.025 and p=0.010). Levels increased over time (p<0.001) and remained
      higher in cSCI versus iSCI (p=0.011) and than in CCS (p<0.001). NfL levels
      correlated with American Spinal Injury Association (ASIA) motor score at baseline
      (r=-0.53, p=0.004) and after 24 h (r=-0.69, p<0.001) and 3-12-month motor outcome
      (baseline NfL: r=-0.43, p=0.026 and 24 h NfL: r=-0.72, p<0.001). Minocycline
      treatment showed decreased NfL levels in the subgroup of cSCI patients.
      CONCLUSIONS: Serum NfL concentrations in SCI patients show a close correlation
      with acute severity and neurological outcome. Our data provide evidence that
      serum NfL is of prognostic value in SCI patients for the first time. Further,
      blood NfL levels may qualify as drug response markers in SCI.

PMID- 24935985
TI  - Anatomic correlates of deep brain stimulation electrode impedance.
AB  - BACKGROUND: The location of the optimal target for deep brain stimulation (DBS)
      of the subthalamic nucleus (STN) remains controversial. Electrode impedance
      affects tissue activation by DBS and has been found to vary by contact number,
      but no studies have examined association between impedance and anatomic location.
      OBJECTIVES: To evaluate the relationship between electrode impedance and anatomic
      contact location, and to assess the clinical significance of impedance. METHODS:
      We gathered retrospective impedance data from 101 electrodes in 73 patients with
      Parkinson's disease. We determined contact location using microelectrode
      recording (MER) and high-field 7T MRI, and assessed the relationship between
      impedance and contact location. RESULTS: For contact location as assessed via
      MER, impedance was significantly higher for contacts in STN, at baseline (111
      Omega vs STN border, p=0.03; 169 Omega vs white matter, p<0.001) and over time
      (90 Omega vs STN border, p<0.001; 54 Omega vs white matter, p<0.001). Over time,
      impedance was lowest in contacts situated at STN border (p=0.03). Impedance did
      not vary by contact location as assessed via imaging. Location determination was
      75% consistent between MER and imaging. Impedance was inversely related to
      absolute symptom reduction during stimulation (-2.5 motor portion of the Unified
      Parkinson's Disease Rating Scale (mUPDRS) points per 1000 Omega, p=0.01).
      CONCLUSIONS: In the vicinity of DBS electrodes chronically implanted in STN,
      impedance is lower at the rostral STN border and in white matter, than in STN.
      This finding suggests that current reaches white matter fibres more readily than
      neuronal cell bodies in STN, which may help explain anatomic variation in
      stimulation efficacy.

PMID- 24935986
TI  - Gene co-expression modules underlying polymorphic and monomorphic zooids in the
      colonial hydrozoan, Hydractinia symbiolongicarpus.
AB  - Advances in sequencing technology have forced a quantitative revolution in
      Evolutionary Biology. One important feature of this renaissance is that
      comprehensive genomic resources can be obtained quickly for almost any taxon,
      thus speeding the development of new model organisms. Here, we analyze 20 RNA-seq
      libraries from morphologically, sexually, and genetically distinct polyp types
      from the gonochoristic colonial hydrozoan, Hydractinia symbiolongicarpus
      (Cnidaria). Analyses of these data using weighted gene co-expression networks
      highlight deeply conserved genetic elements of animal spermatogenesis and
      demonstrate the utility of these methods in identifying modules of genes that
      correlate with different zooid types across various statistical contrasts. RNA
      seq data and analytical scripts described here are deposited in publicly
      available databases. 

PMID- 24935987
TI  - A lack of crowding? Body size does not decrease with density for two behavior
      manipulating parasites.
AB  - For trophically transmitted parasites that manipulate the phenotype of their
      hosts, whether the parasites do or do not experience resource competition depends
      on such factors as the size of the parasites relative to their hosts, the
      intensity of infection, the extent to which parasites share the cost of defending
      against the host's immune system or manipulating their host, and the extent to
      which parasites share transmission goals. Despite theoretical expectations for
      situations in which either no, or positive, or negative density-dependence should
      be observed, most studies document only negative density-dependence for
      trophically transmitted parasites. However, this trend may be an artifact of most
      studies having focused on systems in which parasites are large relative to their
      hosts. Yet, systems are common where parasites are small relative to their hosts,
      and these trophically transmitted parasites may be less likely to experience
      resource limitation. We looked for signs of density-dependence in Euhaplorchis
      californiensis (EUHA) and Renicola buchanani (RENB), two manipulative trematode
      parasites infecting wild-caught California killifish (Fundulus parvipinnis).
      These parasites are small relative to killifish (suggesting resources are not
      limiting), and are associated with changes in killifish behavior that are
      dependent on parasite-intensity and that increase predation rates by the
      parasites' shared final host (indicating the possibility for cost sharing). We
      did not observe negative density-dependence in either species, indicating that
      resources are not limiting. In fact, observed patterns indicate possible mild
      positive density-dependence for EUHA. Although experimental confirmation is
      required, our findings suggest that some behavior-manipulating parasites suffer
      no reduction in size, and may even benefit when "crowded" by conspecifics. 

PMID- 24935988
TI  - The micro and macro of nutrients across biological scales.
AB  - During the past decade, we have gained new insights into the profound effects
      that essential micronutrients and macronutrients have on biological processes
      ranging from cellular function, to whole-organism performance, to dynamics in
      ecological communities, as well as to the structure and function of ecosystems.
      For example, disparities between intake and organismal requirements for specific
      nutrients are known to strongly affect animal physiological performance and
      impose trade-offs in the allocations of resources. However, recent findings have
      demonstrated that life-history allocation trade-offs and even microevolutionary
      dynamics may often be a result of molecular-level constraints on nutrient and
      metabolic processing, in which limiting reactants are routed among competing
      biochemical pathways. In addition, recent work has shown that complex ecological
      interactions between organismal physiological states such as exposure to
      environmental stressors and infectious pathogens can alter organismal
      requirements for, and, processing of, nutrients, and even alter subsequent
      nutrient cycling in ecosystems. Furthermore, new research is showing that such
      interactions, coupled with evolutionary and biogeographical constraints on the
      biosynthesis and availability of essential nutrients and micronutrients play an
      important, but still under-studied role in the structuring and functioning of
      ecosystems. The purpose of this introduction to the symposium "The Micro and
      Macro of Nutrient Effects in Animal Physiology and Ecology" is to briefly review
      and highlight recent research that has dramatically advanced our understanding of
      how nutrients in their varied forms profoundly affect and shape ecological and
      evolutionary processes. 

PMID- 24935989
TI  - A conceptual framework for organismal biology: linking theories, models, and
      data.
AB  - Implicit or subconscious theory is especially common in the biological sciences.
      Yet, theory plays a variety of roles in scientific inquiry. First and foremost,
      it determines what does and does not count as a valid or interesting question or
      line of inquiry. Second, theory determines the background assumptions within
      which inquiries are pursued. Third, theory provides linkages among disciplines.
      For these reasons, it is important and useful to develop explicit theories for
      biology. A general theory of organisms is developed, which includes 10
      fundamental principles that apply to all organisms, and 6 that apply to
      multicellular organisms only. The value of a general theory comes from its
      utility to help guide the development of more specific theories and models. That
      process is demonstrated by examining two domains: ecoimmunology and development.
      For the former, a constitutive theory of ecoimmunology is presented, and used to
      develop a specific model that explains energetic trade-offs that may result from
      an immunological response of a host to a pathogen. For the latter, some of the
      issues involved in trying to devise a constitutive theory that covers all of
      development are explored, and a more narrow theory of phenotypic novelty is
      presented. By its very nature, little of a theory of organisms will be new.
      Rather, the theory presented here is a formal expression of nearly two centuries
      of conceptual advances and practice in research. Any theory is dynamic and
      subject to debate and change. Such debate will occur as part of the present,
      initial formulation, as the ideas presented here are refined. The very process of
      debating the form of the theory acts to clarify thinking. The overarching goal is
      to stimulate debate about the role of theory in the study of organisms, and
      thereby advance our understanding of them. 

PMID- 24935990
TI  - Early biochemical relapse after radical prostatectomy: which prostate cancer
      patients may benefit from a restaging 11C-Choline PET/CT scan before salvage
      radiation therapy?
AB  - The aim of the study was to assess which factors may influence (11)C-choline
      PET/CT detection rate in a population of recurrent prostate cancer (PCa) patients
      listed for salvage radiation therapy (S-RT) in an early phase of biochemical
      relapse, to select which patients could obtain the most benefit by performing
      restaging (11)C-choline PET/CT before S-RT. METHODS: The study comprised 605
      patients, treated with radical prostatectomy (RP) with curative intent for PCa
      who showed rising PSA levels after primary therapy and listed for S-RT. Prostate
      specific antigen (PSA) values were >0.2 ng/mL and <2 ng/mL (mean, 1.05 ng/mL;
      median, 1.07 ng/mL; range, 0.2-2 ng/m; SD, +/-0.59). All patients were classified
      as N0 after RP. Seventeen of 605 patients received adjuvant RT together with RP,
      whereas 148 of 605 patients received androgen-deprivation therapy (ADT) at the
      time of PET/CT. PSA, PSA kinetics, Gleason score, age, time to biochemical
      relapse, ADT, and initial tumor stage were statistically analyzed to assess which
      factor could influence PET/CT positivity and the detection of local versus
      distant relapse. RESULTS: (11)C-choline PET/CT was positive in 28.4% of patients
      (172/605). Eighty-three of 605 patients were positive in the pelvis (group A),
      distant metastasis (group B) were detected in 72 of 605 patients, and local and
      distant sites of relapse were detected in 17 of 605 patients (group C). At
      multivariate analysis, PSA, PSA doubling time (PSAdt), and ongoing ADT were
      significant predictors for positive scan results, whereas PSA and PSAdt were
      significantly related to distant relapse detection (P < 0.05). At the receiver
      operating-characteristic analysis, a PSA value of 1.05 ng/mL and PSAdt of 5.95 mo
      were determined to be the optimal cutoff values in the prediction of a positive
      (11)C-choline PET/CT scan, with an area under the curve (AUC) of 0.625 for PSA
      and 0.677 for PSAdt. CONCLUSION: (11)C-choline PET/CT may be suggested before S
      RT during the early phase of biochemical relapse, to select patients who may
      benefit from this aggressive treatment. Particularly, patients showing fast PSA
      kinetics or PSA increasing levels despite ongoing ADT should be studied with
      (11)C-choline PET/CT before S-RT, considering the higher probability to detect
      positive findings outside the pelvis.

PMID- 24935991
TI  - A compartmental model of mouse thrombopoiesis and erythropoiesis to predict bone
      marrow toxicity after internal irradiation.
AB  - In targeted radionuclide radiotherapy, the relationship between bone marrow (BM)
      toxicity and absorbed dose seems to be elusive. A compartmental model of mouse
      thrombopoiesis and erythropoiesis was set up to predict the depletion of
      hematopoietic cells as a function of the irradiation dose delivered to BM by
      injected radiopharmaceuticals. All simulated kinetics were compared with
      experimental toxicity for several stages of differentiation of the 2
      hematopoietic lineages. METHODS: C57BL/6 mice were injected either with (18)FNa
      (37 and 60 MBq), a bone-seeking agent, or with saline. BM mean absorbed doses
      were calculated according to the MIRD formalism from small-animal PET/CT images.
      Hematologic toxicity was monitored over time, after (18)FNa injection, by
      studying BM progenitors and precursors in addition to blood cells. The
      compartmental model takes into account the pharmacokinetics of the compound, in
      addition to cellular kinetics and cell radiosensitivities for the 2 studied
      lineages. RESULTS: Because biodistribution studies showed an uptake of (18)FNa in
      bones, the skeleton was considered as the principal source organ of BM
      irradiation. The time-activity curve obtained from validated quantification of
      PET/CT images allowed for the calculation of mean absorbed doses to the whole BM
      of 2.1 and 3.4 Gy for (18)FNa injections of 37 and 60 MBq, respectively.
      Concerning hematologic toxicity, the model was in good agreement for the 2
      absorbed doses with experimental measurements of cell depletion for platelets,
      progenitors, and precursors within the BM in terms of time to nadir, depletion
      intensity, and time to recovery. The same agreement was obtained for red blood
      cells and their precursors. Model predictions demonstrated that BM toxicity was
      in correlation with the mean absorbed dose as higher depletions at nadir and
      longer delays to recovery were noticed for 3.4 Gy than for 2.1 Gy. CONCLUSION:
      The developed compartmental model of thrombopoiesis and erythropoiesis in a BM
      toxicity context, after internal irradiation, allowed for the prediction of cell
      kinetics of BM progenitors, precursors, and mature blood cells in a dose
      dependent manner. This model could therefore be used to predict hematologic
      toxicity in preclinical internal radiotherapy to study the dose-response
      relationship.

PMID- 24935992
TI  - Evaluation of 18F-UCB-H as a novel PET tracer for synaptic vesicle protein 2A in
      the brain.
AB  - Synaptic vesicle protein 2 isoforms are critical for proper nervous system
      function and are involved in vesicle trafficking. The synaptic vesicle protein 2A
      (SV2A) isoform has been identified as the binding site of the antiepileptic
      levetiracetam (LEV), making it an interesting therapeutic target for epilepsy.
      (18)F-UCB-H is a novel PET imaging agent with a nanomolar affinity for human
      SV2A. METHODS: Preclinical PET studies were performed with isoflurane
      anesthetized rats. The arterial input function was measured with an arteriovenous
      shunt and a beta-microprobe system. (18)F-UCB-H was injected intravenously (bolus
      of 140 +/- 20 MBq). RESULTS: Brain uptake of (18)F-UCB-H was high, matching the
      expected homogeneous distribution of SV2A. The distribution volume (Vt) for (18)F
      UCB-H was calculated with Logan graphic analysis, and the effect of LEV
      pretreatment on Vt was measured. In control animals the whole-brain Vt was 9.76
      +/- 0.52 mL/cm(3) (mean +/- SD; n = 4; test-retest), and the reproducibility in
      test-retest studies was 10.4% +/- 6.5% (mean +/- SD). The uptake of (18)F-UCB-H
      was dose dependently blocked by pretreatment with LEV (0.1-100 mg/kg
      intravenously). CONCLUSION: Our results indicated that (18)F-UCB-H is a suitable
      radiotracer for the imaging of SV2A in vivo. To our knowledge, this is the first
      PET tracer for the in vivo quantification of SV2A. The necessary steps for the
      implementation of (18)F-UCB-H production under good manufacturing practice
      conditions and the first human studies are being planned.

PMID- 24935994
TI  - Effectiveness of an asthma quality improvement program designed for maintenance
      of certification.
AB  - OBJECTIVE: Pediatricians are required to perform quality improvement for board
      recertification. We developed an asthma project within the Pediatric Physicians'
      Organization at Children's, an independent practice association affiliated with
      Boston Children's Hospital, designed to meet recertification requirements and
      improve asthma care. METHODS: The program was based on the learning collaborative
      model. We developed practice-based registries of children 5 to 17 years of age
      with persistent asthma and helped physicians improve processes of asthma care
      through education, data feedback, and sharing of best practices. RESULTS: Fifty
      six physicians participated in 3 cohorts; 594 patients were included in the
      project. In all cohorts, improvements occurred in the use of asthma action plans
      (62.4%-76.8% cohort 1, 50.6%-88.4% cohort 2, 53.0%-79.6% cohort 3) and Asthma
      Control Tests (4.6%-55.2% cohort 1, 9.0%-67.8% cohort 2, 15.2%-61.4% cohort 3).
      Less consistent improvements were observed in seasonal influenza vaccines,
      controller medications, and asthma follow-up visits. The proportion of patients
      experiencing >=1 asthma exacerbation within the year declined in all 3 cohorts
      (37.8%-19.9%, P = .0002 cohort 1; 27.8%-20.7%, P = .1 cohort 2; 36.6%-26.9%, P =
      .1 cohort 3). For each cohort, asthma exacerbations declined to a greater extent
      than those of a comparison group. CONCLUSIONS: This asthma quality improvement
      project designed for maintenance of certification improved processes of care
      among patients with persistent asthma. The learning collaborative approach may be
      a useful model for other board-recertification quality improvement projects but
      requires a substantial investment of organizational time and staff.

PMID- 24935993
TI  - Effectiveness of anti-TNFalpha for Crohn disease: research in a pediatric
      learning health system.
AB  - OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system
      in the nation and started as a quality improvement collaborative. To test the
      feasibility and validity of using ICN data for clinical research, we evaluated
      the effectiveness of anti-tumor necrosis factor-alpha (anti-TNFalpha) agents in
      the management of pediatric Crohn disease (CD). METHODS: Data were collected in
      35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed
      as a sequence of nonrandomized trials. Patients who had moderate to severe CD
      were classified as initiators or non-initiators of anti-TNFalpha therapy. Among
      4130 patients who had pediatric CD, 603 were new users and 1211 were receiving
      anti-TNFalpha therapy on entry into ICN. RESULTS: During a 26-week follow-up
      period, rate ratios obtained from Cox proportional hazards models, adjusting for
      patient and disease characteristics and concurrent medications, were 1.53 (95%
      confidence interval [CI], 1.20-1.96) for clinical remission and 1.74 (95% CI,
      1.33-2.29) for corticosteroid-free remission. The rate ratio for corticosteroid
      free remission was comparable to the estimate produced by the adult SONIC study,
      which was a randomized controlled trial on the efficacy of anti-TNFalpha therapy.
      The number needed to treat was 5.2 (95% CI, 3.4-11.1) for clinical remission and
      5.0 (95% CI, 3.4-10.0) for corticosteroid-free remission. CONCLUSIONS: In routine
      pediatric gastroenterology practice settings, anti-TNFalpha therapy was effective
      at achieving clinical and corticosteroid-free remission for patients who had
      Crohn disease. Using data from the ICN learning health system for the purpose of
      observational research is feasible and produces valuable new knowledge.

PMID- 24935995
TI  - Adverse childhood experiences of low-income urban youth.
AB  - BACKGROUND AND OBJECTIVE: Current assessments of adverse childhood experiences
      (ACEs) may not adequately encompass the breadth of adversity to which low-income
      urban children are exposed. The purpose of this study was to identify and
      characterize the range of adverse childhood experiences faced by young adults who
      grew up in a low-income urban area. METHODS: Focus groups were conducted with
      young adults who grew up in low-income Philadelphia neighborhoods. Using the
      nominal group technique, participants generated a list of adverse childhood
      experiences and then identified the 5 most stressful experiences on the group
      list. The most stressful experiences identified by participants were grouped into
      a ranked list of domains and subdomains. RESULTS: Participants identified a range
      of experiences, grouped into 10 domains: family relationships, community
      stressors, personal victimization, economic hardship, peer relationships,
      discrimination, school, health, child welfare/juvenile justice, and
      media/technology. Included in these domains were many but not all of the
      experiences from the initial ACEs studies; parental divorce/separation and mental
      illness were absent. Additional experiences not included in the initial ACEs but
      endorsed by our participants included single-parent homes; exposure to violence,
      adult themes, and criminal behavior; personal victimization; bullying; economic
      hardship; and discrimination. CONCLUSIONS: Gathering youth perspectives on
      childhood adversity broadens our understanding of the experience of stress and
      trauma in childhood. Future work is needed to determine the significance of this
      broader set of adverse experiences in predisposing children to poor health
      outcomes as adults.

PMID- 24935996
TI  - Development of guidelines for skeletal survey in young children with fractures.
AB  - OBJECTIVE: To develop guidelines for performing initial skeletal survey (SS) in
      children <24 months old with fractures, based on available evidence and
      collective judgment of experts from diverse pediatric specialties. METHODS:
      Following the Rand/UCLA Method, a multispecialty panel of 13 experts applied
      evidence from a literature review combined with their own expertise in rating the
      appropriateness of performing an SS for 525 clinical scenarios involving
      fractures in children <24 months old. After discussion on the initial ratings,
      panelists re-rated SS appropriateness for 240 revised scenarios and deemed that
      SSs were appropriate in 191 scenarios. The panelists then assessed in which of
      those 191 scenarios SSs were not only appropriate, but also necessary. RESULTS:
      Panelists agreed that SS is "appropriate" for 191 (80%) of 240 scenarios rated
      and "necessary" for 175 (92%) of the appropriate scenarios. Skeletal survey is
      necessary if a fracture is attributed to abuse, domestic violence, or being hit
      by a toy. With few exceptions, SS is necessary in children without a history of
      trauma. In children <12 months old, SS is necessary regardless of the fracture
      type or reported history, with rare exceptions. In children 12 to 23 months old,
      the necessity of obtaining SS is dependent on fracture type. CONCLUSIONS: A
      multispecialty panel reached agreement on multiple clinical scenarios for which
      initial SS is indicated in young children with fractures, allowing for synthesis
      of clinical guidelines with the potential to decrease disparities in care and
      increase detection of abuse.

PMID- 24935997
TI  - Recurrence rates after intussusception enema reduction: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Reported rates of recurrence after enema reduction for
      intussusception are variable. Concerns for recurrence influence postreduction
      management. The objective of this study was to conduct a systematic review and
      meta-analysis to estimate overall, 24-hour, and 48-hour recurrence rates after
      enema reduction in children. METHODS: PubMed, Cochrane Database, and OVID Medline
      were searched from 1946 through December 2011 using the search terms:
      intussusception, recurrence, and enema. Sixty-nine studies of patients age 0 to
      18 years with radiographically proven intussusception reduced by enema that
      report the number of enema reductions and the number of recurrences were
      included. Extraction was done by the primary author (M.P.G.) with 10% of included
      studies independently audited to ensure concordance. RESULTS: Overall recurrence
      rates were 12.7% (95% confidence interval [CI]: 11.1%-14.4%, I2 = 28.8%) for
      contrast enema (CE), 7.5% (95% CI: 5.7%-9.8%, I2 = 52.4%) for ultrasound-guided
      noncontrast enema (UGNCE), and 8.5% (95% CI: 6.9%-10.4%, I2 = 50.1%) for
      fluoroscopy-guided air enema (FGAE). Recurrence rates within 24 hours were 3.9%
      (95% CI: 2.2%-6.7%, I2 = 47.0%) for CE, 3.9% (95% CI: 1.5%-10.1%, I2 = 0.0%) for
      UGNCE, and 2.2% (95% CI: 0.7%-6.5%, I2 = 59.8%) for FGAE. Recurrence rates within
      48 hours were 5.4% (95% CI 3.7%-7.8%, I2 = 32.3%) for CE, 6.6% (95% CI: 4.0%
      10.7%, I2 = 0.0%) for UGNCE, and 2.7% (95% CI: 1.2%-6.5%, I2 = 73.8%) for FGAE.
      Most included studies are retrospective and vary in quality of reporting. Few
      studies reported detailed patient characteristics including timing of
      recurrences. CONCLUSIONS: The risk of early (within 48 hours) recurrence after
      enema reduction is low, suggesting outpatient management of well-appearing
      patients should be considered.

PMID- 24935998
TI  - Demonstrating the learning health system through practical use cases.

PMID- 24935999
TI  - Cardiovascular responses to caffeine by gender and pubertal stage.
AB  - BACKGROUND: Caffeine use is on the rise among children and adolescents. Previous
      studies from our laboratory reported gender differences in the effects of
      caffeine in adolescents. The purpose of this study was to test the hypotheses
      that gender differences in cardiovascular responses to caffeine emerge after
      puberty and that cardiovascular responses to caffeine differ across the phases of
      the menstrual cycle. METHODS: To test these hypotheses, we examined heart rate
      and blood pressure before and after administration of placebo and 2 doses of
      caffeine (1 and 2 mg/kg) in prepubertal (8- to 9-year-olds; n = 52) and
      postpubertal (15- to 17-year-olds; n = 49) boys (n = 54) and girls (n = 47) by
      using a double-blind, placebo-controlled, dose-response design. RESULTS: There
      was an interaction between gender and caffeine dose, with boys having a greater
      response to caffeine than girls. In addition, we found interactions between
      pubertal phase, gender, and caffeine dose, with gender differences present in
      postpubertal, but not in prepubertal, participants. Finally, we found differences
      in responses to caffeine across the menstrual cycle in post-pubertal girls, with
      decreases in heart rate greater in the midluteal phase and blood pressure
      increases greater in the midfollicular phase of the menstrual cycle. CONCLUSIONS:
      These data suggest that gender differences in response to caffeine emerge after
      puberty. Future research will determine the extent to which these gender
      differences are mediated by physiological factors, such as steroid hormones, or
      psychosocial factors, such as more autonomy and control over beverage purchases.

PMID- 24936000
TI  - The medical cost of abusive head trauma in the United States.
AB  - OBJECTIVES: Health consequences of shaken baby syndrome, or pediatric abusive
      head trauma (AHT), can be severe and long-lasting. We aimed to estimate the
      multiyear medical cost attributable to AHT. METHODS: Using Truven Health
      MarketScan data, 2003-2011, we identified children 0 to 4 years old with
      commercial or Medicaid insurance and AHT diagnoses. We used exact case-control
      matching based on demographic and insurance characteristics such as age and
      health plan type to compare medical care between patients with and without AHT
      diagnoses. Using regression models, we assessed service use (ie, average annual
      number of inpatient visits per patient) and inpatient, outpatient (including
      emergency department), drug, and total medical costs attributable to an AHT
      diagnosis during the 4-year period after AHT diagnosis. RESULTS: We assessed 1209
      patients with AHT and 5895 matched controls. Approximately 48% of patients with
      AHT received inpatient care within 2 days of initial diagnosis, and 25% were
      treated in emergency departments. AHT diagnosis was associated with significantly
      greater medical service use and higher inpatient, outpatient, drug, and total
      costs for multiple years after the diagnosis. The estimated total medical cost
      attributable to AHT in the 4 years after diagnosis was $47,952 (95% confidence
      interval [CI], $40,219-$55,685) per patient with AHT (2012 US dollars) and
      differed for commercially insured ($38,231 [95% CI, $29,898-$46,564]) and
      Medicaid ($56,691 [95% CI, $4290-$69,092]) patients. CONCLUSIONS: Children
      continue to have substantial excess medical costs for years after AHT. These
      estimates exclude related nonmedical costs such as special education and
      disability that also are attributable to AHT.

PMID- 24936001
TI  - Linking patient-centered medical home and asthma measures reduces hospital
      readmission rates.
AB  - OBJECTIVE: We sought to achieve 100% compliance with all 3 Children's Asthma Care
      (CAC; CAC-1, CAC-2, CAC-3) measures and track attendance at follow-up
      appointments with the patient-centered medical home. The impact of these measures
      on readmission and emergency department utilization rates was evaluated. METHODS:
      This quality improvement study evaluated compliance with CAC measures in
      pediatric patients aged 2 to 18 years old hospitalized with a primary diagnosis
      of asthma from January 1, 2008, through June 30, 2012. A multidisciplinary Asthma
      Task Force was assembled to develop interventions. Attendance at the follow-up
      appointment was tracked monthly from January 1, 2009. Readmission and emergency
      department utilization rates were compared between the preimplementation period
      (January 1, 2006, through December 31, 2007) and the postimplementation period
      (January 1, 2008, through June 30, 2012). RESULTS: The preimplementation period
      included 231 subjects and the postimplementation period included 532 subjects.
      Compliance with CAC-3 was 95% from October 1, 2009, through June 30, 2012.
      Compliance with the postdischarge follow-up appointment was 69% from January 1,
      2009 through September 30, 2009, increasing significantly to 90% from October 1,
      2009, through June 30, 2012 (P < .001). Postimplementation readmission rates
      significantly decreased in the 91- to 180-day postdischarge interval (odds ratio:
      0.29; 95% confidence interval: 0.11-0.78). CONCLUSIONS: In children hospitalized
      with asthma, compliance with the asthma core measures and the postdischarge
      follow-up appointment with the primary care provider was associated with reduced
      readmission rates at 91 to 180 days after discharge. We attribute our results to
      a comprehensive set of interventions designed by our multidisciplinary Asthma
      Task Force.

PMID- 24936003
TI  - Treatment of tetralogy of Fallot hypoxic spell with intranasal fentanyl.
AB  - We present the case of a 3-month-old girl who had unrepaired Tetralogy of Fallot
      who presented to the emergency department with an acute hypoxic episode. The
      patient was hyperpneic and cyanotic, with an initial oxygen saturation of 56%.
      She did not respond to knee-to-chest positioning. A single dose of intranasal
      fentanyl was administered with subsequent resolution of her symptoms and
      improvement of her oxygen saturation to 78% within 10 minutes. To our knowledge,
      this is the first report of the successful treatment of a hypoxic episode of
      Tetralogy of Fallot using intranasal fentanyl. 

PMID- 24936002
TI  - The association of telomere length with family violence and disruption.
AB  - BACKGROUND: To enhance the understanding of biological mechanisms connecting
      early adversity and negative health, we examine the association between family
      interpersonal violence and disruption and telomere length in youth. These
      specific exposures were selected because of their established links with negative
      health consequences across the life-course. METHODS: Children, age 5 to 15, were
      recruited from the greater New Orleans area, and exposure to family disruption
      and violence was assessed through caregiver report. Telomere length, from buccal
      cell DNA (buccal telomere length [bTL]), was determined by using monochrome
      multiplex quantitative real-time polymerase chain reaction. The association
      between bTL and adversity exposure was tested (n = 80). RESULTS: Cumulative
      exposure to interpersonal violence and family disruption was correlated with bTL.
      Controlling for other sociodemographic factors, bTL was significantly shorter in
      children with higher exposure to family violence and disruption. Witnessing
      family violence exerted a particularly potent impact. A significant gender
      interaction was found (beta = -0.0086, SE = 0.0031, z test= -2.79, P = .0053) and
      analysis revealed the effect only in girls. CONCLUSIONS: bTL is a molecular
      biomarker of adversity and allostatic load that is detectable in childhood. The
      present results extend previous studies by demonstrating that telomeres are
      sensitive to adversity within the overarching family domain. These findings
      suggest that the family ecology may be an important target for interventions to
      reduce the biological impact of adversity in the lives of children.

PMID- 24936004
TI  - Well-child care clinical practice redesign for serving low-income children.
AB  - Our objective was to conduct a rigorous, structured process to create a new model
      of well-child care (WCC) in collaboration with a multisite community health
      center and 2 small, independent practices serving predominantly Medicaid-insured
      children. Working groups of clinicians, staff, and parents (called "Community
      Advisory Boards" [CABs]) used (1) perspectives of WCC stakeholders and (2) a
      literature review of WCC practice redesign to create 4 comprehensive WCC models
      for children ages 0 to 3 years. An expert panel, following a modified version of
      the Rand/UCLA Appropriateness Method, rated each model for potential
      effectiveness on 4 domains: (1) receipt of recommended services, (2) family
      centeredness, (3) timely and appropriate follow-up, and (4) feasibility and
      efficiency. Results were provided to the CABs for selection of a final model to
      implement. The newly developed models rely heavily on a health educator for
      anticipatory guidance and developmental, behavioral, and psychosocial
      surveillance and screening. Each model allots a small amount of time with the
      pediatrician to perform a brief physical examination and to address parents'
      physical health concerns. A secure Web-based tool customizes the visit to
      parents' needs and facilitates previsit screening. Scheduled, non-face-to-face
      methods (text, phone) for parent communication with the health care team are also
      critical to these new models of care. A structured process that engages small
      community practices and community health centers in clinical practice redesign
      can produce comprehensive, site-specific, and innovative models for delivery of
      WCC. This process, as well as the models developed, may be applicable to other
      small practices and clinics interested in practice redesign. 

PMID- 24936006
TI  - Canonical exact coherent structures embedded in high Reynolds number flows.
AB  - The applications and implications of two recently addressed asymptotic
      descriptions of exact coherent structures in shear flows are discussed. The first
      type of asymptotic framework to be discussed was introduced in a series of papers
      by Hall & Smith in the 1990s and was referred to as vortex-wave interaction
      theory (VWI). New results are given here for the canonical VWI problem in an
      infinite region; the results confirm and extend the results for the infinite
      problem inferred the recent VWI computation of plane Couette flow. The results
      given define for the first time exact coherent structures in unbounded flows. The
      second type of canonical structure described here is that recently found for
      asymptomatic suction boundary layer and corresponds to freestream coherent
      structures (FCS), in boundary layer flows. Here, it is shown that the FCS can
      also occur in flows such as Burgers vortex sheet. It is concluded that both
      canonical problems can be locally embedded in general shear flows and thus have
      widespread applicability. 

PMID- 24936007
TI  - Skin friction on a flapping plate in uniform flow.
AB  - To calculate the energy costs of swimming or flying, it is crucial to evaluate
      the drag force originating from skin friction. This topic seems not to have
      received a definite answer, given the difficulty in measuring accurately the
      friction drag along objects in movement. The incoming flow along a flat plate in
      a flapping normal motion has been considered, as limit case of a yawed cylinder
      in uniform flow, and applying the laminar boundary layer assumption it is
      demonstrated that the longitudinal drag scales as the square root of the normal
      velocity component. This lends credit to the assumption that a swimming-like
      motion may induce a drag increase because of the compression of the boundary
      layer, which is known as the 'Bone-Lighthill boundary-layer thinning hypothesis'.
      The boundary-layer model however cannot predict the genuine three-dimensional
      flow dynamics and in particular the friction at the leeward side of the plate. A
      multi-domain, parallel, compact finite-differences Navier-Stokes solution
      procedure is considered, capable of solving the full problem. The time-dependent
      flow dynamics is analysed and the general trends predicted by the simplified
      model are confirmed, with however differences in the magnitude of the friction
      coefficient. A tentative skin friction formula is proposed for flow states along
      a plate moving at steady as well as periodic normal velocities.

PMID- 24936005
TI  - Firearm homicide and other causes of death in delinquents: a 16-year prospective
      study.
AB  - BACKGROUND: Delinquent youth are at risk for early violent death after release
      from detention. However, few studies have examined risk factors for mortality.
      Previous investigations studied only serious offenders (a fraction of the
      juvenile justice population) and provided little data on females. METHODS: The
      Northwestern Juvenile Project is a prospective longitudinal study of health needs
      and outcomes of a stratified random sample of 1829 youth (657 females, 1172
      males; 524 Hispanic, 1005 African American, 296 non-Hispanic white, 4 other
      race/ethnicity) detained between 1995 and 1998. Data on risk factors were drawn
      from interviews; death records were obtained up to 16 years after detention. We
      compared all-cause mortality rates and causes of death with those of the general
      population. Survival analyses were used to examine risk factors for mortality
      after youth leave detention. RESULTS: Delinquent youth have higher mortality
      rates than the general population to age 29 years (P < .05), irrespective of
      gender or race/ethnicity. Females died at nearly 5 times the general population
      rate (P < .05); Hispanic males and females died at 5 and 9 times the general
      population rates, respectively (P < .05). Compared with the general population,
      significantly more delinquent youth died of homicide and its subcategory,
      homicide by firearm (P < .05). Among delinquent youth, racial/ethnic minorities
      were at increased risk of homicide compared with non-Hispanic whites (P < .05).
      Significant risk factors for external-cause mortality and homicide included drug
      dealing (up to 9 years later), alcohol use disorder, and gang membership (up to a
      decade later). CONCLUSIONS: Delinquent youth are an identifiable target
      population to reduce disparities in early violent death.

PMID- 24936008
TI  - Effect of free-stream turbulence on boundary layer transition.
AB  - This paper is concerned with the transition to turbulence in flat plate boundary
      layers due to moderately high levels of free-stream turbulence. The turbulence is
      assumed to be generated by an (idealized) grid and matched asymptotic expansions
      are used to analyse the resulting flow over a finite thickness flat plate located
      in the downstream region. The characteristic Reynolds number Rlambda based on the
      mesh size lambda and free-stream velocity is assumed to be large, and the
      turbulence intensity epsilon is assumed to be small. The asymptotic flow
      structure is discussed for the generic case where the turbulence Reynolds number
      epsilonRlambda and the plate thickness and are held fixed (at O(1) and O(lambda),
      respectively) in the limit as [Formula: see text] and epsilon->0. But various
      limiting cases are considered in order to explain the relevant transition
      mechanisms. It is argued that there are two types of streak-like structures that
      can play a role in the transition process: (i) those that appear in the
      downstream region and are generated by streamwise vorticity in upstream flow and
      (ii) those that are concentrated near the leading edge and are generated by plate
      normal vorticity in upstream flow. The former are relatively unaffected by
      leading edge geometry and are usually referred to as Klebanoff modes while the
      latter are strongly affected by leading edge geometry and are more streamwise
      vortex-like in appearance. 

PMID- 24936009
TI  - Collisions, rebounds and skimming.
AB  - Repeated oblique impacts and rebounds of a solid body or bodies on horizontal
      shallow water are investigated through mathematical modelling. The inclinations
      from the horizontal are supposed small as the skimming evolves, for a thin
      typical body shape. The new formulation aimed at improved prediction as well as
      the background involved is presented together with nonlinear analysis and
      computation. Comparatively fast or slow collisions and rebounds are found to be
      of special interest over short time-scales.

PMID- 24936010
TI  - Triple-deck analysis of transonic high Reynolds number flow through slender
      channels.
AB  - In this work, laminar transonic weakly three-dimensional flows at high Reynolds
      numbers in slender channels, as found in microsupersonic nozzles and
      turbomachines of micro-electro-mechanical systems, are considered. The channel
      height is taken so small that the viscous wall layers forming at the channel
      walls start to interact strongly rather than weakly with the inviscid core flow
      and, therefore, the classical boundary layer approach fails. The resulting
      viscous-inviscid interaction problem is formulated using matched asymptotic
      expansions and found to be governed by a triple-deck structure. As a consequence,
      the properties of the predominantly inviscid core region and the viscous wall
      layers have to be calculated simultaneously in the interaction region. Weakly
      three-dimensional effects caused by surface roughness, upstream propagating flow
      perturbations, boundary layer separation as well as bifurcating solutions are
      discussed. Representative results for subsonic as well as supersonic conditions
      are presented, and the importance of these flow phenomena in technical
      applications as, for example, a means to reduce shock losses through the use of
      deformed geometry is addressed. 

PMID- 24936011
TI  - Unsteady separation in vortex-induced boundary layers.
AB  - This paper provides a brief review of the analytical and numerical developments
      related to unsteady boundary-layer separation, in particular as it relates to
      vortex-induced flows, leading up to our present understanding of this important
      feature in high-Reynolds-number, surface-bounded flows in the presence of an
      adverse pressure gradient. In large part, vortex-induced separation has been the
      catalyst for pulling together the theory, numerics and applications of unsteady
      separation. Particular attention is given to the role that Prof. Frank T. Smith,
      FRS, has played in these developments over the course of the past 35 years. The
      following points will be emphasized: (i) unsteady separation plays a pivotal role
      in a wide variety of high-Reynolds-number flows, (ii) asymptotic methods have
      been instrumental in elucidating the physics of both steady and unsteady
      separation, (iii) Frank T. Smith has served as a catalyst in the application of
      asymptotic methods to high-Reynolds-number flows, and (iv) there is still much
      work to do in articulating a complete theoretical understanding of unsteady
      boundary-layer separation.

PMID- 24936012
TI  - On the role of acoustic feedback in boundary-layer instability.
AB  - In this paper, the classical triple-deck formalism is employed to investigate two
      instability problems in which an acoustic feedback loop plays an essential role.
      The first concerns a subsonic boundary layer over a flat plate on which two well
      separated roughness elements are present. A spatially amplifying Tollmien
      Schlichting (T-S) wave between the roughness elements is scattered by the
      downstream roughness to emit a sound wave that propagates upstream and impinges
      on the upstream roughness to regenerate the T-S wave, thereby forming a closed
      feedback loop in the streamwise direction. Numerical calculations suggest that,
      at high Reynolds numbers and for moderate roughness heights, the long-range
      acoustic coupling may lead to absolute instability, which is characterized by
      self-sustained oscillations at discrete frequencies. The dominant peak frequency
      may jump from one value to another as the Reynolds number, or the distance
      between the roughness elements, is varied gradually. The second problem concerns
      the supersonic 'twin boundary layers' that develop along two well-separated
      parallel flat plates. The two boundary layers are in mutual interaction through
      the impinging and reflected acoustic waves. It is found that the interaction
      leads to a new instability that is absent in the unconfined boundary layer. 

PMID- 24936013
TI  - On recent developments in marginal separation theory.
AB  - Thin aerofoils are prone to localized flow separation at their leading edge if
      subjected to moderate angles of attack alpha. Although 'laminar separation
      bubbles' at first do not significantly alter the aerofoil performance, they tend
      to 'burst' if alpha is increased further or if perturbations acting upon the flow
      reach a certain intensity. This then either leads to global flow separation
      (stall) or triggers the laminar-turbulent transition process within the boundary
      layer flow. This paper addresses the asymptotic analysis of the early stages of
      the latter phenomenon in the limit as the characteristic Reynolds number
      [Formula: see text], commonly referred to as marginal separation theory. A new
      approach based on the adjoint operator method is presented that enables the
      fundamental similarity laws of marginal separation theory to be derived and the
      analysis to be extended to higher order. Special emphasis is placed on the
      breakdown of the flow description, i.e. the formation of finite-time
      singularities (a manifestation of the bursting process), and on its resolution
      being based on asymptotic arguments. The passage to the subsequent triple-deck
      stage is described in detail, which is a prerequisite for carrying out a future
      numerical treatment of this stage in a proper way. Moreover, a composite
      asymptotic model is developed in order for the inherent ill-posedness of the
      Cauchy problems associated with the current flow description to be resolved. 

PMID- 24936014
TI  - Polynomial sum of squares in fluid dynamics: a review with a look ahead.
AB  - The first part of this paper reviews the application of the sum-of-squares-of
      polynomials technique to the problem of global stability of fluid flows. It
      describes the known approaches and the latest results, in particular, obtaining
      for a version of the rotating Couette flow a better stability range than the
      range given by the classic energy stability method. The second part of this paper
      describes new results and ideas, including a new method of obtaining bounds for
      time-averaged flow parameters illustrated with a model problem and a method of
      obtaining approximate bounds that are insensitive to unstable steady states and
      periodic orbits. It is proposed to use the bound on the energy dissipation rate
      as the cost functional in the design of flow control aimed at reducing turbulent
      drag. 

PMID- 24936015
TI  - Stability, separation and close body interactions. Introduction.

PMID- 24936016
TI  - Instability of supersonic compression ramp flow.
AB  - The instability of supersonic compression ramp flow is investigated. It is
      assumed that the Reynolds number is large and that the governing equations are
      the unsteady triple-deck equations. The mean flow is first calculated by solving
      the steady equations for various scaled ramp angles alpha, and the numerical
      results suggest that there is no singularity for increasing ramp angles. The
      stability of the flow is investigated using two approaches, first by solving the
      linearized unsteady equations and looking for global modes proportional to
      e(lambdat). In the second approach, the linearized unsteady equations are solved
      numerically with various initial conditions. Whereas no globally unsteady modes
      could be found for the range of ramp angles studied, the numerical simulations
      show the formation of wavepacket type disturbances which grow and convect and
      reach large amplitudes. However, the numerical results show large variations with
      grid size even on very fine grids.

PMID- 24936017
TI  - Some observations regarding steady laminar flows past bluff bodies.
AB  - Steady laminar flows past simple objects, such as a cylinder or a sphere, have
      been studied for well over a century. Theoretical, experimental and numerical
      methods have all contributed fundamentally towards our understanding of the
      resulting flows. This article focuses on developments during the past few
      decades, when mostly numerical and asymptotical advances have provided insights
      also for steady, although unstable, high-Reynolds-numbers flow regimes. 

PMID- 24936018
TI  - Magnetohydrodynamic channel flows with weak transverse magnetic fields.
AB  - Magnetohydrodynamic flow of an incompressible fluid through a plane channel with
      slowly varying walls and a magnetic field applied transverse to the channel is
      investigated in the high Reynolds number limit. It is found that the magnetic
      field can first influence the hydrodynamic flow when the Hartmann number reaches
      a sufficiently large value. The magnetic field is found to suppress the steady
      and unsteady viscous flow near the channel walls unless the wall shapes become
      large. 

PMID- 24936019
TI  - On the generation of nonlinear travelling waves in confined geometries using
      electric fields.
AB  - We investigate electrostatically induced interfacial instabilities and subsequent
      generation of nonlinear coherent structures in immiscible, viscous, dielectric
      multi-layer stratified flows confined in small-scale channels. Vertical electric
      fields are imposed across the channel to produce interfacial instabilities that
      would normally be absent in such flows. In situations when the imposed vertical
      fields are constant, interfacial instabilities emerge due to the presence of
      electrostatic forces, and we follow the nonlinear dynamics via direct numerical
      simulations. We also propose and illustrate a novel pumping mechanism in
      microfluidic devices that does not use moving parts. This is achieved by first
      inducing interfacial instabilities using constant background electric fields to
      obtain fully nonlinear deformations. The second step involves the manipulation of
      the imposed voltage on the lower electrode (channel wall) to produce a spatio
      temporally varying voltage there, in the form of a travelling wave with pre
      determined properties. Such travelling wave dielectrophoresis methods are shown
      to generate intricate fluid-surface-structure interactions that can be of
      practical value since they produce net mass flux along the channel and thus are
      candidates for microfluidic pumps without moving parts. We show via extensive
      direct numerical simulations that this pumping phenomenon is a result of an
      externally induced nonlinear travelling wave that forms at the fluid-fluid
      interface and study the characteristics of the generated velocity field inside
      the channel. 

PMID- 24936020
TI  - Gross separation approaching a blunt trailing edge as the turbulence intensity
      increases.
AB  - A novel rational description of incompressible two-dimensional time-mean
      turbulent boundary layer (BL) flow separating from a bluff body at an arbitrarily
      large globally formed Reynolds number, Re, is devised. Partly in contrast to and
      partly complementing previous approaches, it predicts a pronounced delay of
      massive separation as the turbulence intensity level increases. This is bounded
      from above by a weakly decaying Re-dependent gauge function (hence, the BL
      approximation stays intact locally), and thus the finite intensity level
      characterizing fully developed turbulence. However, it by far exceeds the
      moderate level found in a preceding study which copes with the associated
      moderate delay of separation. Thus, the present analysis bridges this self
      consistent and another forerunner theory, proposing extremely retarded separation
      by anticipating a fully attached external potential flow. Specifically, it is
      shown upon formulation of a respective distinguished limit at which rate the
      separation point and the attached-flow trailing edge collapse as [Formula: see
      text] and how on a short streamwise scale the typical small velocity deficit in
      the core region of the incident BL evolves to a large one. Hence, at its base,
      the separating velocity profile varies generically with the one-third power of
      the wall distance, and the classical triple-deck problem describing local viscous
      inviscid interaction crucial for moderately retarded separation is superseded by
      a Rayleigh problem, governing separation of that core layer. Its targeted
      solution proves vital for understanding the separation process more close to the
      wall. Most importantly, the analysis does not resort to any specific turbulence
      closure. A first comparison with the available experimentally found positions of
      separation for the canonical flow past a circular cylinder is encouraging.

PMID- 24936021
TI  - Comparative survey of outdoor, residential and workplace radon concentrations.
AB  - This study investigated radon concentrations in above-ground (i.e. first floor)
      workplace in Missouri and compared them with above-ground radon concentrations in
      nearby homes and outdoor locations. This study also examined the potential
      utility of using home and outdoor radon concentrations to predict the radon
      concentration at a nearby workplace (e.g. county agencies and schools). Even
      though workplace radon concentrations were not statistically different from home
      radon concentrations, the radon concentration at a particular home, or outdoor
      location, was a poor predictor of the radon concentration at a nearby workplace.
      Overall, 9.6 and 9.9 % of homes and workplace, respectively, exhibited radon
      concentrations of >=148 Bq m(-3). Because of the percentage of workplace with
      elevated radon concentrations, the results suggest that additional surveys of
      workplace radon concentrations are needed, especially in areas of high radon
      potential, to assess the contribution of workplace radon exposure to an
      individual's overall radon exposure. 

PMID- 24936022
TI  - Evaluation of human exposure to complex waveform magnetic fields generated by arc
      welding equipment according to European safety standards.
AB  - In this paper, a procedure is described for the assessment of human exposure to
      magnetic fields with complex waveforms generated by arc-welding equipment. The
      work moves from the analysis of relevant guidelines and technical standards,
      underlining their strengths and their limits. Then, the procedure is described
      with particular attention to the techniques used to treat complex waveform
      fields. Finally, the procedure is applied to concrete cases encountered in the
      workplace. The discussion of the results highlights the critical points in the
      procedure, as well as those related to the evolution of the technical and
      exposure standards. 

PMID- 24936024
TI  - The Importance of Talk Therapy.

PMID- 24936025
TI  - Schizophrenia and Vision of My Life.

PMID- 24936023
TI  - Reduced dopamine transporter expression in the amygdala of subjects diagnosed
      with schizophrenia.
AB  - A disruption of dopaminergic transmission in the amygdala of subjects with
      schizophrenia was proposed as a main contributor to pathophysiological and
      clinical manifestations of this disorder. We tested the hypothesis that the
      expression of the dopamine transporter (DAT) is decreased in the amygdala of
      subjects with schizophrenia. In normal control, schizophrenic subjects and
      bipolar disorder subjects, we measured numerical density of axon varicosities
      immunoreactive (IR) for DAT in the lateral (LN), basal, accessory basal (ABN),
      and cortical (CO) nuclei and intercalated cell masses (ITCM) of the amygdala.
      Tyrosine hydroxylase (TH)-IR and dopamine beta-hydroxylase (DBH)-IR varicosities
      were measured to test for potential loss of varicosities and serotonin
      transporter (5HTT)-IR for involvement of the serotoninergic system. Among several
      potential confounding variables tested, particular emphasis was placed on
      exposure to therapeutic drugs. In schizophrenic subjects, DAT-IR varicosities
      were decreased in LN (P = .0002), ABN (P = .013), and CO (P = .0001) in
      comparison with controls, and in comparison with bipolar disorder subjects in LN
      (P = .004) and CO (P = .002). DBH-IR varicosities were decreased in ABN (P =
      .008) and ITCM (P = .017), compared with controls. TH- and 5HTT-IR varicosities
      were not altered. No changes were detected in bipolar disorder. Taken together
      with TH and DBH findings, reductions of DAT-IR varicosities point to decreased
      DAT expression in dopaminergic terminals in the amygdala of subjects with
      schizophrenia. This DAT decrease may disrupt dopamine uptake, leading to
      increased dopaminergic synaptic transmission and spillage into the extracellular
      space with activation of extrasynaptic dopamine receptors. Concurrent decrease of
      noradrenaline in the ABN may disrupt memory consolidation. 

PMID- 24936026
TI  - Naturally occurring diseases in animals: contributions to translational medicine.

PMID- 24936028
TI  - Naturally occurring cancers in dogs: insights for translational genetics and
      medicine.
AB  - Here, we briefly review the state of knowledge of human cancer genetics to
      elaborate on the need for different types of mammalian models, highlighting the
      strengths of the dog. Mouse models are unparalleled for their experimental
      tractability and rapid genetic manipulation but have some key limitations in the
      area of human relevance. Companion dog models are attractive, because they are
      genetically more similar to humans, share environmental exposures with their
      owners, suffer from the same diseases as humans, and receive a high level of
      health care. They are ideal for the study of chronic diseases, because they age
      five to eight times faster than humans and generally live to old age. In
      addition, each dog breed is on the order of 100-fold genetically simpler than the
      whole human or dog population. These traits make the dog ideal for the study of
      complex genetics of naturally occurring cancers. Here, we contrast the relative
      strengths of cancer genetics in humans and dogs. We propose that humans are most
      ideal for the study of somatic cancer genetics, whereas dogs are most ideal for
      germline genetics. That proposition is supported by comparison of genome-wide
      association studies (GWASs) in human and canine cancer. One of the advantages of
      dog cancer GWASs is the ability to rapidly map complex traits, conduct fine
      mapping and identification of causative variation, and thus be in a position to
      move on to functional studies. We mention how these strengths of dog models will
      lead to rapid advances in translational medicine. 

PMID- 24936029
TI  - Bartonellosis: one health perspectives for an emerging infectious disease.
AB  - In recent years, an increasing number of Bartonella species have been identified
      as zoonotic pathogens, transmitted by animal bites, scratches, arthropods and
      even by needle sticks. Considering the diversity of newly discovered Bartonella
      species and subspecies and the large number and ecologically diverse animal
      reservoir hosts and the evolving spectrum of arthropod vectors that can transmit
      these bacteria among animals and humans, the clinical and diagnostic challenges
      posed by Bartonella transmission in nature are presumably much more complex than
      is currently appreciated by diagnosticians, vector biologists, ecologists,
      physicians, or veterinarians. Historically the term "bartonellosis" was
      attributed to infections with Bartonella bacilliformis, transmitted by sandflies
      in the Peruvian Andes. Currently, however, bartonellosis now includes infections
      caused by any Bartonella sp. anywhere in the world. Potentially, because
      Bartonella spp. can infect erythrocytes, endothelial cells, pericytes, CD34(+)
      progenitor cells, and various macrophage-type cells, including microglial cells,
      dendritic cells, and circulating monocytes in vitro, the clinical and
      pathological manifestations of bartonellosis appear to be very diverse in both
      sick animals and human patients. Because 75% of emerging infectious diseases are
      zoonoses, many of which are vector-transmitted by an arthropod, a One Health
      approach to bartonellosis and other zoonotic infections is needed to properly
      address animal health, public health, and environmental factors that influence
      the distribution and transmission of these bacteria. The One Health concept
      encourages a spirit of cooperation among animal, environmental, and human health
      professionals and promotes developing integrated solutions for complex problems
      that impact the health of animals, humans, and the planet. Importantly,
      substantial research is needed to define the medical importance of this genus as
      a cause of animal and human illnesses. 

PMID- 24936027
TI  - Lamb model of respiratory syncytial virus-associated lung disease: insights to
      pathogenesis and novel treatments.
AB  - Preterm birth is a risk factor for respiratory syncytial virus (RSV)
      bronchiolitis and hospitalization. The pathogenesis underlying this is not fully
      understood, and in vivo studies are needed to better clarify essential cellular
      features and molecular mechanisms. Such studies include analysis of lung tissue
      from affected human infants and various animal models. The preterm and newborn
      lamb lung has developmental, structural, cellular, physiologic, and immunologic
      features similar to that of human infants. Also, the lamb lung is susceptible to
      various strains of RSV that infect infants and cause similar bronchiolar lesions.
      Studies in lambs suggest that viral replication in airways (especially
      bronchioles) is extensive by 4 days after infection, along with bronchiolitis
      characterized by degeneration and necrosis of epithelial cells, syncytial cell
      formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia,
      and innate and adaptive immune responses. RSV bronchiolitis greatly affects
      airflow and gaseous exchange. RSV disease severity is increased in preterm lambs
      compared with full-term lambs; similar to human infants. The lamb is conducive to
      experimental assessment of novel, mechanistic therapeutic interventions such as
      delivery of vascular endothelial growth factor and enhancement of airway
      epithelial oxidative responses, Club (Clara) cell protein 10, and synthesized
      compounds such as nanobodies. In contrast, exposure of the fetal ovine lung in
      vivo to ethanol, a risk factor for preterm birth, reduces pulmonary alveolar
      development and surfactant protein A expression. Because the formalin-inactivated
      RSV vaccination enhances some inflammatory responses to RSV infection in lambs,
      this model has the potential to assess mechanisms of formalin-inactivated RSV
      enhanced disease as well as newly developed vaccines. 

PMID- 24936031
TI  - Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology.
AB  - Osteosarcoma (OSA) is the most common form of malignant bone cancer in children
      and dogs, although the disease occurs in dogs approximately 10 times more
      frequently than in people. Multidrug chemotherapy and aggressive surgical
      techniques have improved survival; however, new therapies for OSA are critical,
      as little improvement in survival times has been achieved in either dogs or
      people over the past 15 years, even with significant efforts directed at the
      incorporation of novel therapeutic approaches. Both clinical and molecular
      evidence suggests that human and canine OSA share many key features, including
      tumor location, presence of microscopic metastatic disease at diagnosis,
      development of chemotherapy-resistant metastases, and altered
      expression/activation of several proteins (e.g. Met, ezrin, phosphatase and
      tensin homolog, signal transducer and activator of transcription 3), and p53
      mutations, among others. Additionally, canine and pediatric OSA exhibit
      overlapping transcriptional profiles and shared DNA copy number aberrations,
      supporting the notion that these diseases are similar at the molecular level.
      This review will discuss the similarities between pediatric and canine OSA with
      regard to histology, biologic behavior, and molecular genetic alterations that
      indicate canine OSA is a relevant, spontaneous, large animal model of the
      pediatric disease and outline how the study of naturally occurring OSA in dogs
      will offer additional insights into the biology and future treatment of this
      disease in both children and dogs. 

PMID- 24936032
TI  - Achilles tendon injuries in elite athletes: lessons in pathophysiology from their
      equine counterparts.
AB  - Superficial digital flexor tendon (SDFT) injury in equine athletes is one of the
      most well-accepted, scientifically supported companion animal models of human
      disease (i.e., exercise-induced Achilles tendon [AT] injury). The SDFT and AT are
      functionally and clinically equivalent (and important) energy-storing structures
      for which no equally appropriate rodent, rabbit, or other analogues exist. Access
      to equine tissues has facilitated significant advances in knowledge of tendon
      maturation and aging, determination of specific exercise effects (including early
      life), and definition of some of the earliest stages of subclinical pathology.
      Access to human surgical biopsies has provided complementary information on more
      advanced phases of disease. Importantly, equine SDFT injuries are only a model
      for acute ruptures in athletes, not the entire spectrum of human tendonopathy
      (including chronic tendon pain). In both, pathology begins with a potentially
      prolonged phase of accumulation of (subclinical) microdamage. Recent work has
      revealed remarkably similar genetic risk factors, including further evidence that
      tenocyte dysfunction plays an active role. Mice are convenient but not
      necessarily accurate models for multiple diseases, particularly at the cellular
      level. Mechanistic studies, including tendon cell responses to combinations of
      exercise-associated stresses, require a more thorough investigation of cross
      species conservation of key stress pathway auditors. Molecular evidence has
      provided some context for the poor performance of mouse models; equines may
      provide better systems at this level. The use of horses may be additionally
      justifiable based on comparable species longevity, lifestyle factors, and
      selection pressure by similar infectious agents (e.g., herpesviruses) on general
      cell stress pathway evolution. 

PMID- 24936030
TI  - Domestic dogs and cancer research: a breed-based genomics approach.
AB  - Domestic dogs are unique from other animal models of cancer in that they
      generally experience spontaneous disease. In addition, most types of cancer
      observed in humans are found in dogs, suggesting that canines may be an
      informative system for the study of cancer genetics. Domestic dogs are divided
      into over 175 breeds, with members of each breed sharing significant phenotypes.
      The breed barrier enhances the utility of the model, especially for genetic
      studies where small numbers of genes are hypothesized to account for the breed
      cancer susceptibility. These facts, combined with recent advances in high
      throughput sequencing technologies allows for an unrivaled ability to use pet dog
      populations to find often subtle mutations that promote cancer susceptibility and
      progression in dogs as a whole. The meticulous record keeping associated with dog
      breeding makes the model still more powerful, as it facilitates both association
      analysis and family-based linkage studies. Key to the success of these studies is
      their cooperative nature, with owners, scientists, veterinarians and breed clubs
      working together to avoid the cost and unpopularity of developing captive
      populations. In this article we explore these principals and advocate for colony
      free, genetic studies that will enhance our ability to diagnose and treat cancer
      in dogs and humans alike. 

PMID- 24936033
TI  - Urinary bladder cancer in dogs, a naturally occurring model for cancer biology
      and drug development.
AB  - Each year more than 65,000 people are diagnosed with urinary bladder cancer, and
      more than 14,000 people die from the disease in the United States. Studies in
      relevant animal models are essential to improve the management of bladder cancer.
      Naturally occurring bladder cancer in dogs very closely mimics human invasive
      bladder cancer, specifically high-grade invasive transitional cell carcinoma
      (TCC; also referred to as invasive urothelial carcinoma) in cellular and
      molecular features; biological behavior, including sites and frequency of
      metastasis; and response to therapy. Canine bladder cancer complements
      experimentally induced rodent tumors in regard to animal models of bladder
      cancer. Results of cellular and molecular studies and -omics analyses in dogs are
      expected to lead to improved detection of TCC and preneoplastic lesions, earlier
      intervention, better prediction of patient outcome, and more effective TCC
      management overall. Studies in dogs are being used to help define heritable risks
      (through very strong breed-associated risk) and environment risks and to evaluate
      prevention and treatment approaches that benefit humans as well as dogs. Clinical
      treatment trials in pet dogs with TCC are considered a win-win scenario by
      clinician scientists and pet owners. The individual dog benefits from effective
      treatment, the results are expected to help other dogs, and the findings are
      expected to ultimately help humans with TCC. This article provides an overview of
      canine TCC, a summary of the similarities and differences between canine and
      human invasive TCC, and examples of the types of valuable translational research
      that can be done using dogs with naturally occurring TCC. 

PMID- 24936035
TI  - Naturally occurring spinal hyperostosis in dogs as a model for human spinal
      disorders.
AB  - Both spondylosis and diffuse idiopathic skeletal hyperostosis (DISH) are
      prevalent in humans and are considered distinct entities. Nowadays, the term
      spondylosis is in the biomedical literature mostly used when concurrently
      degenerative disc disease is present. In companion animals, many reports on
      spondylosis, often without intervertebral disc degeneration, are described. The
      nomenclature and the definitions of both spondylosis and DISH in biomedical and
      veterinary literature should be more in line to facilitate comparison.
      Spondylosis and DISH occur in dogs spontaneously and can co-occur in one animal.
      Specifically, Boxers may serve as translational disease models for the
      elucidation of the gene(s) involved in the (etio)pathogenesis of spondylosis and
      DISH or serve as a test population for newly developed treatment options. 

PMID- 24936036
TI  - Cancer and comparative imaging.
AB  - Comparative oncology research is gaining traction as a method for streamlining
      the drug discovery and development strategies currently in place worldwide. This
      approach uses the tumor-bearing pet dog as a relevant and complementary model
      alongside the traditional use of rodents, no-human primates, and other large
      mammalian species such as purpose-bred dogs or pigs. To date, most comparative
      oncology studies have been designed and executed to evaluate new anticancer drugs
      using tumor-bearing dogs with specific naturally occurring cancers as models for
      humans. These studies have proved extremely valuable for modeling pharmacokinetic
      pharmacodynamic relationships, refining drug doses and schedules, and validating
      an individual drug's target in vivo. The National Cancer Institute's Comparative
      Oncology Trials Consortium (http://ccr.cancer.gov/resources/cop/COTC.asp) is a
      cooperative effort that provides infrastructure and resources to support this
      effort. To complement ongoing efforts in this field, we propose expansion of
      comparative cancer imaging as a component to drug discovery and development.
      Diagnostic imaging is critical to diagnosis and management of malignancy in both
      humans and animals. Molecular imaging techniques allow for detection of disease
      specific signals that provide individualized data to aid in patient selection,
      response to therapy, and prognostication. In this review, we will highlight the
      comparative oncology studies that have used molecular imaging techniques,
      demonstrating the value of spontaneous canine cancers as a research tool in drug
      and imaging agent development. 

PMID- 24936037
TI  - Developing T cell cancer immunotherapy in the dog with lymphoma.
AB  - Immunotherapy is not a new concept for veterinary medicine; however, adoptive T
      cell therapy is a new area of research in humans and canines alike. In humans, T
      cell therapy has been used against many different tumor histologies, including
      lymphoma, melanoma, and colon cancer. Although in dogs this approach has
      currently only been applied to lymphoma, other tumor types are under
      investigation. There are many different strategies used to take advantage of cell
      mediated antitumor properties of T cells. This review will discuss many of the
      current strategies used in both humans and canines in regards to adoptive T cell
      therapy. 

PMID- 24936038
TI  - Canine epilepsy: an underutilized model.
AB  - The mainstay of comparative research for epilepsy has been rodent models of
      induced epilepsy. This rodent basic science is essential, but it does not always
      translate to similar results in people, likely because induced epilepsy is not
      always similar enough to naturally occurring epilepsy. A good large animal,
      intermediate model would be very helpful to potentially bridge this translational
      gap. Epilepsy is the most common medical neurologic disease of dogs. It has been
      proposed since the 1970s that dogs with naturally occurring epilepsy could
      potentially be used as a comparative model for people of the underlying basis and
      therapy of epilepsy. There have been sporadic studies in the decades since then,
      with a relative surge in the last 10 years. These canine studies in the areas of
      genetics, drug therapy, dietary therapy, electroencelphalogram research, and
      devices for epilepsy show proof of concept that canine epilepsy can be a very
      good model for comparative research for many, but not all, facets of epilepsy.
      Results of research in canine epilepsy can and have benefited the improvement of
      treatment for both people and dogs. 

PMID- 24936040
TI  - Issues related to institutional animal care and use committees and clinical
      trials using privately owned animals.

PMID- 24936039
TI  - Naturally occurring animal models of human hepatitis E virus infection.
AB  - Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the
      family Hepeviridae. Hepatitis E caused by HEV is a clinically important global
      disease. There are currently four well-characterized genotypes of HEV in
      mammalian species, although numerous novel strains of HEV likely belonging to
      either new genotypes or species have recently been identified from several other
      animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas
      genotypes 3 and 4 infect an expanding host range of animal species and are
      zoonotic to humans. Historical animal models include various species of nonhuman
      primates, which have been indispensable for the discovery of human HEV and for
      understanding its pathogenesis and course of infection. With the genetic
      identification and characterization of animal strains of HEV, a number of
      naturally occurring animal models such as swine, chicken, and rabbit have
      recently been developed for various aspects of HEV research, including vaccine
      trials, pathogenicity, cross-species infection, mechanism of virus replication,
      and molecular biology studies. Unfortunately, the current available animal models
      for HEV are still inadequate for certain aspects of HEV research. For instance,
      an animal model is still lacking to study the underlying mechanism of severe and
      fulminant hepatitis E during pregnancy. Also, an animal model that can mimic
      chronic HEV infection is critically needed to study the mechanism leading to
      chronicity in immunocompromised individuals. Genetic identification of additional
      novel animal strains of HEV may lead to the development of better naturally
      occurring animal models for HEV. This article reviews the current understanding
      of animal models of HEV infection in both natural and experimental infection
      settings and identifies key research needs and limitations. 

PMID- 24936034
TI  - Pharmacologic management of Duchenne muscular dystrophy: target identification
      and preclinical trials.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked human disorder in which absence
      of the protein dystrophin causes degeneration of skeletal and cardiac muscle. For
      the sake of treatment development, over and above definitive genetic and cell
      based therapies, there is considerable interest in drugs that target downstream
      disease mechanisms. Drug candidates have typically been chosen based on the
      nature of pathologic lesions and presumed underlying mechanisms and then tested
      in animal models. Mammalian dystrophinopathies have been characterized in mice
      (mdx mouse) and dogs (golden retriever muscular dystrophy [GRMD]). Despite
      promising results in the mdx mouse, some therapies have not shown efficacy in
      DMD. Although the GRMD model offers a higher hurdle for translation, dogs have
      primarily been used to test genetic and cellular therapies where there is greater
      risk. Failed translation of animal studies to DMD raises questions about the
      propriety of methods and models used to identify drug targets and test efficacy
      of pharmacologic intervention. The mdx mouse and GRMD dog are genetically
      homologous to DMD but not necessarily analogous. Subcellular species differences
      are undoubtedly magnified at the whole-body level in clinical trials. This
      problem is compounded by disparate cultures in clinical trials and preclinical
      studies, pointing to a need for greater rigor and transparency in animal
      experiments. Molecular assays such as mRNA arrays and genome-wide association
      studies allow identification of genetic drug targets more closely tied to disease
      pathogenesis. Genes in which polymorphisms have been directly linked to DMD
      disease progression, as with osteopontin, are particularly attractive targets. 

PMID- 24936050
TI  - Brucella abortus depends on pyruvate phosphate dikinase and malic enzyme but not
      on Fbp and GlpX fructose-1,6-bisphosphatases for full virulence in laboratory
      models.
AB  - The brucellae are the etiological agents of brucellosis, a worldwide-distributed
      zoonosis. These bacteria are facultative intracellular parasites and thus are
      able to adjust their metabolism to the extra- and intracellular environments
      encountered during an infectious cycle. However, this aspect of Brucella biology
      is imperfectly understood, and the nutrients available in the intracellular niche
      are unknown. Here, we investigated the central pathways of C metabolism used by
      Brucella abortus by deleting the putative fructose-1,6-bisphosphatase (fbp and
      glpX), phosphoenolpyruvate carboxykinase (pckA), pyruvate phosphate dikinase
      (ppdK), and malic enzyme (mae) genes. In gluconeogenic but not in rich media,
      growth of DeltappdK and Deltamae mutants was severely impaired and growth of the
      double Deltafbp-DeltaglpX mutant was reduced. In macrophages, only the DeltappdK
      and Deltamae mutants showed reduced multiplication, and studies with the
      DeltappdK mutant confirmed that it reached the replicative niche. Similarly, only
      the DeltappdK and Deltamae mutants were attenuated in mice, the former being
      cleared by week 10 and the latter persisting longer than 12 weeks. We also
      investigated the glyoxylate cycle. Although aceA (isocitrate lyase) promoter
      activity was enhanced in rich medium, aceA disruption had no effect in vitro or
      on multiplication in macrophages or mouse spleens. The results suggest that B.
      abortus grows intracellularly using a limited supply of 6-C (and 5-C) sugars that
      is compensated by glutamate and possibly other amino acids entering the Krebs
      cycle without a critical role of the glyoxylate shunt. 

PMID- 24936051
TI  - Hypoxia-activated cytochrome bd expression in Mycobacterium smegmatis is cyclic
      AMP receptor protein dependent.
AB  - Mycobacteria are obligate aerobes and respire using two terminal respiratory
      oxidases, an aa3-type cytochrome c oxidase and a cytochrome bd-type menaquinol
      oxidase. Cytochrome bd is encoded by cydAB from the cydABDC gene cluster that is
      conserved throughout the mycobacterial genus. Here we report that cydAB and cydDC
      in Mycobacterium smegmatis constitute two separate operons under hypoxic growth
      conditions. The transcriptional start sites of both operons were mapped, and a
      series of cydA-lacZ and cydD-lacZ transcriptional reporter fusions were made to
      identify regulatory promoter elements. A 51-bp region was identified in the cydAB
      promoter that was required for maximal cydA-lacZ expression in response to
      hypoxia. A cyclic AMP receptor protein (CRP)-binding site (viz. GTGAN6CCACC) was
      identified in this region, and mutation of this site to CCCAN6CTTTC abolished
      cydA-lacZ expression in response to hypoxia. Binding of purified CRP (MSMEG_0539)
      to the cydAB promoter DNA was analyzed using electrophoretic mobility shift
      assays. CRP binding was dependent on GTGAN6CCACC and showed cyclic AMP (cAMP)
      dependency. No CRP site was present in the cydDC promoter, and a 10-bp inverted
      repeat (CGGTGGTACCGGTACCACCG) was required for maximal cydD-lacZ expression.
      Taken together, the data indicate that CRP is a direct regulator of cydAB
      expression in response to hypoxia and that the regulation of cydDC expression is
      CRP independent and under the control of an unknown regulator. 

PMID- 24936052
TI  - Ammonium metabolism enzymes aid Helicobacter pylori acid resistance.
AB  - The gastric pathogen Helicobacter pylori possesses a highly active urease to
      support acid tolerance. Urea hydrolysis occurs inside the cytoplasm, resulting in
      the production of NH3 that is immediately protonated to form NH4 (+). This
      ammonium must be metabolized or effluxed because its presence within the cell is
      counterproductive to the goal of raising pH while maintaining a viable proton
      motive force (PMF). Two compatible hypotheses for mitigating intracellular
      ammonium toxicity include (i) the exit of protonated ammonium outward via the
      UreI permease, which was shown to facilitate diffusion of both urea and ammonium,
      and/or (ii) the assimilation of this ammonium, which is supported by evidence
      that H. pylori assimilates urea nitrogen into its amino acid pools. We
      investigated the second hypothesis by constructing strains with altered
      expression of the ammonium-assimilating enzymes glutamine synthetase (GS) and
      glutamate dehydrogenase (GDH) and the ammonium-evolving periplasmic enzymes
      glutaminase (Ggt) and asparaginase (AsnB). H. pylori strains expressing elevated
      levels of either GS or GDH are more acid tolerant than the wild type, exhibit
      enhanced ammonium production, and are able to alkalize the medium faster than the
      wild type. Strains lacking the genes for either Ggt or AsnB are acid sensitive,
      have 8-fold-lower urea-dependent ammonium production, and are more acid sensitive
      than the parent. Additionally, we found that purified H. pylori GS produces
      glutamine in the presence of Mg(2+) at a rate similar to that of unadenylated
      Escherichia coli GS. These data reveal that all four enzymes contribute to whole
      cell acid resistance in H. pylori and are likely important for assimilation
      and/or efflux of urea-derived ammonium. 

PMID- 24936053
TI  - Unique helicase determinants in the essential conjugative TraI factor from
      Salmonella enterica serovar Typhimurium plasmid pCU1.
AB  - The widespread development of multidrug-resistant bacteria is a major health
      emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic
      resistance genes, also encode the protein factors necessary to orchestrate the
      propagation of plasmid DNA between bacterial cells through conjugative transfer.
      Successful conjugative DNA transfer depends on key catalytic components to nick
      one strand of the duplex DNA plasmid and separate the DNA strands while cell-to
      cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid
      pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA
      nicking relaxase and ATP-dependent helicase domains within a single, 1,078
      residue polypeptide. In this work, we unraveled the helicase determinants of
      Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation
      assays. TraI binds DNA substrates with high affinity in a manner influenced by
      nucleic acid length and the presence of a DNA hairpin structure adjacent to the
      nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase
      motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short
      (144-residue) domain at the extreme C terminus of the protein severely diminishes
      ATP-dependent strand separation. Collectively, these data define the helicase
      motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a
      previously uncharacterized C-terminal functional domain that uncouples ATP
      hydrolysis from strand separation activity. 

PMID- 24936054
TI  - AraC/XylS family stress response regulators Rob, SoxS, PliA, and OpiA in the fire
      blight pathogen Erwinia amylovora.
AB  - Transcriptional regulators of the AraC/XylS family have been associated with
      multidrug resistance, organic solvent tolerance, oxidative stress, and virulence
      in clinically relevant enterobacteria. In the present study, we identified four
      homologous AraC/XylS regulators, Rob, SoxS, PliA, and OpiA, from the fire blight
      pathogen Erwinia amylovora Ea1189. Previous studies have shown that the
      regulators MarA, Rob, and SoxS from Escherichia coli mediate multiple-antibiotic
      resistance, primarily by upregulating the AcrAB-TolC efflux system. However, none
      of the four AraC/XylS regulators from E. amylovora was able to induce a multidrug
      resistance phenotype in the plant pathogen. Overexpression of rob led to a 2-fold
      increased expression of the acrA gene. However, the rob-overexpressing strain
      showed increased resistance to only a limited number of antibiotics. Furthermore,
      Rob was able to induce tolerance to organic solvents in E. amylovora by
      mechanisms other than efflux. We demonstrated that SoxS from E. amylovora is
      involved in superoxide resistance. A soxS-deficient mutant of Ea1189 was not able
      to grow on agar plates supplemented with the superoxide-generating agent
      paraquat. Furthermore, expression of soxS was induced by redox cycling agents. We
      identified two novel members of the AraC/XylS family in E. amylovora. PliA was
      highly upregulated during the early infection phase in apple rootstock and
      immature pear fruits. Multiple compounds were able to induce the expression of
      pliA, including apple leaf extracts, phenolic compounds, redox cycling agents,
      heavy metals, and decanoate. OpiA was shown to play a role in the regulation of
      osmotic and alkaline pH stress responses. 

PMID- 24936055
TI  - Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by
      recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.
AB  - Strict regulation of intra- and extracellular pH is an important determinant of
      nervous system function as many voltage-, ligand-, and H(+)-gated cationic
      channels are exquisitely sensitive to transient fluctuations in pH elicited by
      neural activity and pathophysiologic events such as hypoxia-ischemia and
      seizures. Multiple Na(+)/H(+) exchangers (NHEs) are implicated in maintenance of
      neural pH homeostasis. However, aside from the ubiquitous NHE1 isoform, their
      relative contributions are poorly understood. NHE5 is of particular interest as
      it is preferentially expressed in brain relative to other tissues. In hippocampal
      neurons, NHE5 regulates steady-state cytoplasmic pH, but intriguingly the bulk of
      the transporter is stored in intracellular vesicles. Here, we show that NHE5 is a
      direct target for phosphorylation by the AMP-activated protein kinase (AMPK), a
      key sensor and regulator of cellular energy homeostasis in response to metabolic
      stresses. In NHE5-transfected non-neuronal cells, activation of AMPK by the AMP
      mimetic AICAR or by antimycin A, which blocks aerobic respiration and causes
      acidification, increased cell surface accumulation and activity of NHE5, and
      elevated intracellular pH. These effects were effectively blocked by the AMPK
      antagonist compound C, the NHE inhibitor HOE694, and mutation of a predicted AMPK
      recognition motif in the NHE5 C terminus. This regulatory pathway was also
      functional in primary hippocampal neurons, where AMPK activation of NHE5
      protected the cells from sustained antimycin A-induced acidification. These data
      reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of
      hippocampal neurons during metabolic stress.

PMID- 24936057
TI  - ZIP2 protein, a zinc transporter, is associated with keratinocyte
      differentiation.
AB  - Zinc is essential for the proper functioning of various enzymes and transcription
      factors, and its homeostasis is rigorously controlled by zinc transporters
      (SLC39/ZIP, importers; SLC30/ZnT, exporters). Skin disease is commonly caused by
      a zinc deficiency. Dietary and inherited zinc deficiencies are known to cause
      alopecia and the development of vesicular or pustular dermatitis. A previous
      study demonstrated that zinc played crucial roles in the survival of
      keratinocytes and their unique functions. High levels of zinc have been detected
      in the epidermis. Epidermal layers are considered to use a mechanism that
      preferentially takes in zinc, which is involved with the unique functions of
      keratinocytes. However, few studies have investigated the ZIP (Zrt- and Irt-like
      protein) proteins specifically expressed in keratinocytes and their functions. We
      explored the ZIP proteins specifically expressed in the epidermis and analyzed
      their functions. Gene expression analysis showed that the expression of ZIP2 was
      consistently higher in the epidermis than in the dermis. Immunohistochemistry
      analysis confirmed the expression of ZIP2 in differentiating keratinocytes. The
      expression of ZIP2 was found to be up-regulated by the differentiation induction
      of cultured keratinocytes. Intracellular zinc levels were decreased in
      keratinocytes when ZIP2 was knocked down by siRNA, and this subsequently
      inhibited the differentiation of keratinocytes. Moreover, we demonstrated that
      ZIP2 knockdown inhibited the normal formation of a three-dimensional cultured
      epidermis. Taken together, the results of this study suggest that ZIP2, a zinc
      transporter expressed specifically in the epidermis, and zinc taken up by ZIP2
      are necessary for the differentiation of keratinocytes. 

PMID- 24936056
TI  - The prolyl peptidases PRCP/PREP regulate IRS-1 stability critical for rapamycin
      induced feedback activation of PI3K and AKT.
AB  - The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT)/mammalian
      target of rapamycin (mTOR) pathway conveys signals from receptor tyrosine kinases
      (RTKs) to regulate cell metabolism, proliferation, survival, and motility.
      Previously we found that prolylcarboxypeptidase (PRCP) regulate proliferation and
      survival in breast cancer cells. In this study, we found that PRCP and the
      related family member prolylendopeptidase (PREP) are essential for proliferation
      and survival of pancreatic cancer cells. Depletion/inhibition of PRCP and PREP
      induced serine phosphorylation and degradation of IRS-1, leading to inactivation
      of the cellular PI3K and AKT. Notably, depletion/inhibition of PRCP/PREP
      destabilized IRS-1 in the cells treated with rapamycin, blocking the feedback
      activation PI3K/AKT. Consequently, inhibition of PRCP/PREP enhanced rapamycin
      induced cytotoxicity. Thus, we have identified PRCP and PREP as a stabilizer of
      IRS-1 which is critical for PI3K/AKT/mTOR signaling in pancreatic cancer cells. 

PMID- 24936058
TI  - Role of protein phosphatase 1 in dephosphorylation of Ebola virus VP30 protein
      and its targeting for the inhibition of viral transcription.
AB  - The filovirus Ebola (EBOV) causes the most severe hemorrhagic fever known. The
      EBOV RNA-dependent polymerase complex includes a filovirus-specific VP30, which
      is critical for the transcriptional but not replication activity of EBOV
      polymerase; to support transcription, VP30 must be in a dephosphorylated form.
      Here we show that EBOV VP30 is phosphorylated not only at the N-terminal serine
      clusters identified previously but also at the threonine residues at positions
      143 and 146. We also show that host cell protein phosphatase 1 (PP1) controls
      VP30 dephosphorylation because expression of a PP1-binding peptide cdNIPP1
      increased VP30 phosphorylation. Moreover, targeting PP1 mRNA by shRNA resulted in
      the overexpression of SIPP1, a cytoplasm-shuttling regulatory subunit of PP1, and
      increased EBOV transcription, suggesting that cytoplasmic accumulation of PP1
      induces EBOV transcription. Furthermore, we developed a small molecule compound,
      1E7-03, that targeted a non-catalytic site of PP1 and increased VP30
      dephosphorylation. The compound inhibited the transcription but increased
      replication of the viral genome and completely suppressed replication of EBOV in
      cultured cells. Finally, mutations of Thr(143) and Thr(146) of VP30 significantly
      inhibited EBOV transcription and strongly induced VP30 phosphorylation in the N
      terminal Ser residues 29-46, suggesting a novel mechanism of regulation of VP30
      phosphorylation. Our findings suggest that targeting PP1 with small molecules is
      a feasible approach to achieve dysregulation of the EBOV polymerase activity.
      This novel approach may be used for the development of antivirals against EBOV
      and other filovirus species. 

PMID- 24936059
TI  - The role of a novel auxiliary pocket in bacterial phenylalanyl-tRNA synthetase
      druggability.
AB  - The antimicrobial activity of phenyl-thiazolylurea-sulfonamides against
      Staphylococcus aureus PheRS are dependent upon phenylalanine levels in the
      extracellular fluids. Inhibitor efficacy in animal models of infection is
      substantially diminished by dietary phenylalanine intake, thereby reducing the
      perceived clinical utility of this inhibitor class. The search for novel
      antibacterial compounds against Gram-negative pathogens led to a re-evaluation of
      this phenomenon, which is shown here to be unique to S. aureus. Inhibition of
      macromolecular syntheses and characterization of novel resistance mutations in
      Escherichia coli demonstrate that antimicrobial activity of phenyl-thiazolylurea
      sulfonamides is mediated by PheRS inhibition, validating this enzyme as a viable
      drug discovery target for Gram-negative pathogens. A search for novel inhibitors
      of PheRS yielded three novel chemical starting points. NMR studies were used to
      confirm direct target engagement for phenylalanine-competitive hits. The
      crystallographic structure of Pseudomonas aeruginosa PheRS defined the binding
      modes of these hits and revealed an auxiliary hydrophobic pocket that is
      positioned adjacent to the phenylalanine binding site. Three viable inhibitor
      resistant mutants were mapped to this pocket, suggesting that this region is a
      potential liability for drug discovery. 

PMID- 24936060
TI  - Peripheral benzodiazepine receptor/translocator protein global knock-out mice are
      viable with no effects on steroid hormone biosynthesis.
AB  - Translocator protein (TSPO), previously known as the peripheral benzodiazepine
      receptor, is a mitochondrial outer membrane protein implicated as essential for
      cholesterol import to the inner mitochondrial membrane, the rate-limiting step in
      steroid hormone biosynthesis. Previous research on TSPO was based entirely on in
      vitro experiments, and its critical role was reinforced by an early report that
      claimed TSPO knock-out mice were embryonic lethal. In a previous publication, we
      examined Leydig cell-specific TSPO conditional knock-out mice that suggested TSPO
      was not required for testosterone production in vivo. This raised controversy and
      several questions regarding TSPO function. To examine the definitive role of TSPO
      in steroidogenesis and embryo development, we generated global TSPO null (Tspo(-/
      )) mice. Contrary to the early report, Tspo(-/-) mice survived with no apparent
      phenotypic abnormalities and were fertile. Examination of adrenal and gonadal
      steroidogenesis showed no defects in Tspo(-/-) mice. Adrenal transcriptome
      comparison of gene expression profiles showed that genes involved in steroid
      hormone biosynthesis (Star, Cyp11a1, and Hsd3b1) were unchanged in Tspo(-/-)
      mice. Adrenocortical ultrastructure illustrated no morphological alterations in
      Tspo(-/-) mice. In an attempt to correlate our in vivo findings to previously
      used in vitro models, we also determined that siRNA knockdown or the absence of
      TSPO in different mouse and human steroidogenic cell lines had no effect on
      steroidogenesis. These findings directly refute the dogma that TSPO is
      indispensable for steroid hormone biosynthesis and viability. By amending the
      current model, this study advances our understanding of steroidogenesis with
      broad implications in biology and medicine. 

PMID- 24936061
TI  - A combined "omics" approach identifies N-Myc interactor as a novel cytokine
      induced regulator of IRE1 protein and c-Jun N-terminal kinase in pancreatic beta
      cells.
AB  - Type 1 diabetes is an autoimmune disease with a strong inflammatory component.
      The cytokines interleukin-1beta and interferon-gamma contribute to beta cell
      apoptosis in type 1 diabetes. These cytokines induce endoplasmic reticulum stress
      and the unfolded protein response (UPR), contributing to the loss of beta cells.
      IRE1alpha, one of the UPR mediators, triggers insulin degradation and
      inflammation in beta cells and is critical for the transition from
      "physiological" to "pathological" UPR. The mechanisms regulating inositol
      requiring protein 1alpha (IRE1alpha) activation and its signaling for beta cell
      "adaptation," "stress response," or "apoptosis" remain to be clarified. To
      address these questions, we combined mammalian protein-protein interaction trap
      based IRE1alpha interactome and functional genomic analysis of human and rodent
      beta cells exposed to pro-inflammatory cytokines to identify novel cytokine
      induced regulators of IRE1alpha. Based on this approach, we identified N-Myc
      interactor (NMI) as an IRE1alpha-interacting/modulator protein in rodent and
      human pancreatic beta cells. An increased expression of NMI was detected in
      islets from nonobese diabetic mice with insulitis and in rodent or human beta
      cells exposed in vitro to the pro-inflammatory cytokines interleukin-1beta and
      interferon-gamma. Detailed mechanistic studies demonstrated that NMI negatively
      modulates IRE1alpha-dependent activation of JNK and apoptosis in rodent and human
      pancreatic beta cells. In conclusion, by using a combined omics approach, we
      identified NMI induction as a novel negative feedback mechanism that decreases
      IRE1alpha-dependent activation of JNK and apoptosis in cytokine-exposed beta
      cells

PMID- 24936063
TI  - Translation elongation factor 1A mutants with altered actin bundling activity
      show reduced aminoacyl-tRNA binding and alter initiation via eIF2alpha
      phosphorylation.
AB  - Apart from its canonical function in translation elongation, eukaryotic
      translation elongation factor 1A (eEF1A) has been shown to interact with the
      actin cytoskeleton. Amino acid substitutions in eEF1A that reduce its ability to
      bind and bundle actin in vitro cause improper actin organization in vivo and
      reduce total translation. Initial in vivo analysis indicated the reduced
      translation was through initiation. The mutant strains exhibit increased levels
      of phosphorylated initiation factor 2alpha (eIF2alpha) dependent on the presence
      of the general control non-derepressible 2 (Gcn2p) protein kinase. Gcn2p causes
      downregulation of total protein synthesis at initiation in response to increases
      in deacylated tRNA levels in the cell. Increased levels of eIF2alpha
      phosphorylation are not due to a general reduction in translation elongation as
      eEF2 and eEF3 mutants do not exhibit this effect. Deletion of GCN2 from the eEF1A
      actin bundling mutant strains revealed a second defect in translation. The eEF1A
      actin-bundling proteins exhibit changes in their elongation activity at the level
      of aminoacyl-tRNA binding in vitro. These findings implicate eEF1A in a feedback
      mechanism for regulating translation at initiation.

PMID- 24936062
TI  - F-box only protein 31 (FBXO31) negatively regulates p38 mitogen-activated protein
      kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and
      degradation of mitogen-activated protein kinase kinase 6 (MKK6).
AB  - The p38 MAPK signal transduction pathway plays an important role in inflammatory
      and stress responses. MAPKK6 (MKK6), a dual specificity protein kinase, is a p38
      activator. Activation of the MKK6-p38 pathway is kept in check by multiple layers
      of regulations, including autoinhibition, dimerization, scaffold proteins, and
      Lys-63-linked polyubiquitination. However, the mechanisms underlying deactivation
      of MKK6-p38, which is crucial for maintaining the magnitude and duration of
      signal transduction, are not well understood. Lys-48-linked ubiquitination, which
      marks substrates for proteasomal degradation, is an important negative
      posttranslational regulatory machinery for signal pathway transduction. Here we
      report that the accumulation of F-box only protein 31 (FBXO31), a component of
      Skp1 . Cul1 . F-box protein E3 ligase, negatively regulated p38 activation in
      cancer cells upon genotoxic stresses. Our results show that FBXO31 binds to MKK6
      and mediates its Lys-48-linked polyubiquitination and degradation, thereby
      functioning as a negative regulator of MKK6-p38 signaling and protecting cells
      from stress-induced cell apoptosis. Taken together, our findings uncover a new
      mechanism of deactivation of MKK6-p38 and substantiate a novel regulatory role of
      FBXO31 in stress response.

PMID- 24936064
TI  - Interleukin-1beta reduces L-type Ca2+ current through protein kinase Cepsilon
      activation in mouse heart.
AB  - Inflammation is now widely recognized as a key component of heart disease.
      Patients suffering from arrhythmias and heart failure have increased levels of
      tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta). Evidence
      suggests that these cytokines are important mediators of cardiac remodeling;
      however, their effects on ion channels and arrhythmogenesis remain incompletely
      understood. The L-type Ca(2+) current (ICaL) is a major determinant of the
      plateau phase of cardiac action potential and has a critical excitation
      contraction coupling role. Thus, altering its properties could have detrimental
      effects on cardiac electrical and contractile functions. Accordingly, the
      objective of this study was to elucidate the effect of TNFalpha and IL-1beta on
      ICaL, while exploring the underlying regulatory mechanisms. Neonatal mouse
      ventricular myocytes were treated with a pathophysiological concentration (30
      pg/ml) of TNFalpha and IL-1beta for 24 h. Voltage-clamp recordings showed that
      TNFalpha had no effect on ICaL, whereas IL-1beta decreased the current density by
      36%. Although both IL-1beta- and TNFalpha-treated myocytes showed significant
      increase in reactive oxidative species (ROS), Western blot experiments revealed
      that only IL-1beta increased PKCepsilon membrane translocation. The antioxidant N
      acetyl-L-cysteine normalized ROS levels and restored ICaL density. Furthermore,
      the PKCepsilon translocation inhibitor epsilon-V1-2 blocked the effect of IL
      1beta on ICaL. The reduction of ICaL by IL-1beta was also seen in cultured adult
      ventricular myocytes. Overall, chronic IL-1beta treatment decreased ICaL density
      in cardiomyocytes. These effects implicated ROS signaling and PKCepsilon
      activation. These findings could contribute to explain the role of IL-1beta in
      the development of arrhythmia and heart failure.

PMID- 24936065
TI  - Regulation of endothelial cell barrier function by antibody-driven affinity
      modulation of platelet endothelial cell adhesion molecule-1 (PECAM-1).
AB  - PECAM-1 is a 130-kDa member of the immunoglobulin (Ig) superfamily that is
      expressed on the surface of platelets and leukocytes, and at the intracellular
      junctions of confluent endothelial cell monolayers. Previous studies have shown
      that PECAM-1/PECAM-1 homophilic interactions play a key role in leukocyte
      transendothelial migration, in allowing PECAM-1 to serve as a mechanosensory
      complex in endothelial cells, in its ability to confer cytoprotection to
      proapoptotic stimuli, and in maintaining endothelial cell junctional integrity.
      To examine the adhesive properties of full-length PECAM-1 in a native lipid
      environment, we purified it from platelets and assembled it into phospholipid
      nanodiscs. PECAM-1-containing nanodiscs retained not only their ability to bind
      homophilically to PECAM-1-expressing cells, but exhibited regulatable adhesive
      interactions that could be modulated by ligands that bind membrane- proximal Ig
      Domain 6. This property was exploited to enhance the rate of barrier restoration
      in endothelial cell monolayers subjected to inflammatory challenge. The finding
      that the adhesive properties of PECAM-1 are regulatable suggests novel approaches
      for controlling endothelial cell migration and barrier function in a variety of
      vascular permeability disorders.

PMID- 24936066
TI  - Intricate protein-protein interactions in the cyanobacterial circadian clock.
AB  - The cyanobacterial circadian clock consists of a post-translational oscillator
      (PTO) and a PTO-dependent transcription-translation feedback loop (TTFL). The PTO
      can be reconstituted in vitro with the KaiA, KaiB, and KaiC proteins, enabling
      detailed biochemical and biophysical investigations. Both the CI and the CII
      halves of the KaiC hexamer harbor ATPases, but only the C-terminal CII ring
      exhibits kinase and phospho-transferase activities. KaiA stimulates the kinase
      and KaiB associates with KaiC during the dephosphorylation phase and sequesters
      KaiA. Recent research has led to conflicting models of the KaiB-KaiC interaction,
      precluding a clear understanding of KaiB function and KaiABC clock mechanism. 

PMID- 24936067
TI  - Structure of a novel O-linked N-acetyl-D-glucosamine (O-GlcNAc) transferase,
      GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat
      adhesins.
AB  - Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a
      critical role in various biological processes. In Streptococcus pneumoniae, the
      core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the
      serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat
      protein), which is involved in the infection and pathogenesis. Here we report the
      2.0 A crystal structure of GtfA, revealing a beta-meander add-on domain beyond
      the catalytic domain. It represents a novel add-on domain, which is distinct from
      the all-alpha-tetratricopeptide repeats in the only two structure-known OGTs.
      Structural analyses combined with binding assays indicate that this add-on domain
      contributes to forming an active GtfA-GtfB complex and recognizing the acceptor
      protein. In addition, the in vitro glycosylation system enables us to map the O
      linkages to the serine residues within the first SRR of PsrP. These findings
      suggest that fusion with an add-on domain might be a universal mechanism for
      diverse OGTs that recognize varying acceptor proteins/peptides.

PMID- 24936069
TI  - Non-equivalent ligand selectivity of agonist sites in (alpha4beta2)2alpha4
      nicotinic acetylcholine receptors: a key determinant of agonist efficacy.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is the most abundant
      nAChR type in the brain, and this receptor type exists in alternate
      (alpha4beta2)2alpha4 and (alpha4beta2)2beta2 forms, which are activated by
      agonists with strikingly differing efficacies. Recent breakthroughs have
      identified an additional operational agonist binding site in the
      (alpha4beta2)2alpha4 nAChR that is responsible for the signature sensitivity of
      this receptor to activation by agonists, yet the structural mechanisms
      determining agonist efficacy at this receptor type are not yet fully understood.
      In this study, we characterized the ligand selectivity of the individual agonist
      sites of the (alpha4beta2)2alpha4 nAChR to determine whether differences in
      agonist selectivity influence agonist efficacy. Applying the substituted cysteine
      accessibility method to individual agonist sites in concatenated
      (alpha4beta2)2alpha4 receptors, we determined the agonist selectivity of the
      agonist sites of the (alpha4beta2)2alpha4 receptor. We show that (a)
      accessibility of substituted cysteines to covalent modification by
      methanesulfonate reagent depends on the agonist site at which the modification
      occurs and (b) that agonists such as sazetidine-A and TC-2559 are excluded from
      the site at the alpha4/alpha4 interface. Given that additional binding to the
      agonist site in the alpha4/alpha4 interface increases acetylcholine efficacy and
      that agonists excluded from the agonist site at the alpha4/alpha4 interface
      behave as partial agonists, we conclude that the ability to engage all agonist
      sites in (alpha4beta2)2alpha4 nAChRs is a key determinant of agonist efficacy.
      The findings add another level of complexity to the structural mechanisms that
      govern agonist efficacy in heteromeric nAChRs and related ligand-gated ion
      channels. 

PMID- 24936079
TI  - Special supplement introduction: hallucinations.
AB  - This Special Supplement presents reports from 11 working groups of the
      interdisciplinary International Consortium on Hallucination Research meeting in
      Durham, UK, September 2013. Topics include psychological therapies for auditory
      hallucinations, culture and hallucinations, hallucinations in children and
      adolescents, visual hallucinations, interdisciplinary approaches to the
      phenomenology of auditory verbal hallucinations (AVHs), AVHs in persons without
      need for care, a multisite study of the PSYRATS instrument, subtypes of AVHs, the
      Hearing Voices Movement, Research Domain Criteria for hallucinations, and
      cortical specialization as a route to understanding hallucinations.

PMID- 24936068
TI  - B-Raf regulation of integrin alpha4beta1-mediated resistance to shear stress
      through changes in cell spreading and cytoskeletal association in T cells.
AB  - The regulation of integrin-mediated adhesion is of vital importance to adaptive
      and innate immunity. Integrins are versatile proteins and mediate T cell
      migration and trafficking by binding to extracellular matrix or other cells as
      well as initiating intracellular signaling cascades promoting survival or
      activation. The MAPK pathway is known to be downstream from integrins and to
      regulate survival, differentiation, and motility. However, secondary roles for
      canonical MAPK pathway members are being discovered. We show that chemical
      inhibition of RAF by sorafenib or shRNA-mediated knockdown of B-Raf reduces T
      cell resistance to shear stress to alpha4beta1 integrin ligands vascular cell
      adhesion molecule 1 (VCAM-1) and fibronectin, whereas inhibition of MEK/ERK by
      U0126 had no effect. Microscopy showed that RAF inhibition leads to significant
      inhibition of T cell spreading on VCAM-1. The association of alpha4beta1 integrin
      with the actin cytoskeleton was shown to be dependent on B-Raf activity or
      expression, whereas alpha4beta1 integrin affinity for soluble VCAM-1 was not.
      These effects were shown to be specific for alpha4beta1 integrin and not other
      integrins, such as alpha5beta1 or LFA-1, or a variety of membrane proteins. We
      demonstrate a novel role for B-Raf in the selective regulation of alpha4beta1
      integrin-mediated adhesion. 

PMID- 24936070
TI  - The H50Q mutation enhances alpha-synuclein aggregation, secretion, and toxicity.
AB  - Over the last two decades, the identification of missense mutations in the alpha
      synuclein (alpha-Syn) gene SNCA in families with inherited Parkinson disease (PD)
      has reinforced the central role of alpha-Syn in PD pathogenesis. Recently, a new
      missense mutation (H50Q) in alpha-Syn was described in patients with a familial
      form of PD and dementia. Here we investigated the effects of this novel mutation
      on the biophysical properties of alpha-Syn and the consequences for its cellular
      function. We found that the H50Q mutation affected neither the structure of free
      or membrane-bound alpha-Syn monomer, its interaction with metals, nor its
      capacity to be phosphorylated in vitro. However, compared with the wild-type (WT)
      protein, the H50Q mutation accelerated alpha-Syn fibrillization in vitro. In cell
      based models, H50Q mutation did not affect alpha-Syn subcellular localization or
      its ability to be phosphorylated by PLK2 and GRK6. Interestingly, H50Q increased
      alpha-Syn secretion from SHSY5Y cells into culture medium and induced more
      mitochondrial fragmentation in hippocampal neurons. Although the transient
      overexpression of WT or H50Q did not induce toxicity, both species induced
      significant cell death when added to the culture medium of hippocampal neurons.
      Strikingly, H50Q exhibited more toxicity, suggesting that the H50Q-related
      enhancement of alpha-Syn aggregation and secretion may play a role in the
      extracellular toxicity of this mutant. Together, our results provide novel
      insight into the mechanism by which this newly described PD-associated mutation
      may contribute to the pathogenesis of PD and related disorders. 

PMID- 24936080
TI  - The search for elusive structure: a promiscuous realist case for researching
      specific psychotic experiences such as hallucinations.
AB  - Problems in psychiatric classification have impeded research into psychopathology
      for more than a century. Here, I briefly review several new approaches to solving
      this problem, including the internalizing-externalizing-psychosis spectra, the 5
      factor model of psychotic symptoms, and the more recent network approach.
      Researchers and clinicians should probably adopt an attitude of promiscuous
      realism and assume that a single classification system is unlikely to be
      effective for all purposes, and that different systems will need to be chosen for
      research into etiology, public mental health research, and clinical activities.
      Progress in understanding the risk factors and mechanisms that lead to
      psychopathology is most likely to be achieved by focusing on specific types of
      experience or symptoms such as hallucinations.

PMID- 24936081
TI  - Psychological therapies for auditory hallucinations (voices): current status and
      key directions for future research.
AB  - This report from the International Consortium on Hallucinations Research
      considers the current status and future directions in research on psychological
      therapies targeting auditory hallucinations (hearing voices). Therapy approaches
      have evolved from behavioral and coping-focused interventions, through
      formulation-driven interventions using methods from cognitive therapy, to a
      number of contemporary developments. Recent developments include the application
      of acceptance- and mindfulness-based approaches, and consolidation of methods for
      working with connections between voices and views of self, others, relationships
      and personal history. In this article, we discuss the development of therapies
      for voices and review the empirical findings. This review shows that
      psychological therapies are broadly effective for people with positive symptoms,
      but that more research is required to understand the specific application of
      therapies to voices. Six key research directions are identified: (1) moving
      beyond the focus on overall efficacy to understand specific therapeutic processes
      targeting voices, (2) better targeting psychological processes associated with
      voices such as trauma, cognitive mechanisms, and personal recovery, (3) more
      focused measurement of the intended outcomes of therapy, (4) understanding
      individual differences among voice hearers, (5) extending beyond a focus on
      voices and schizophrenia into other populations and sensory modalities, and (6)
      shaping interventions for service implementation.

PMID- 24936082
TI  - Culture and hallucinations: overview and future directions.
AB  - A number of studies have explored hallucinations as complex experiences involving
      interactions between psychological, biological, and environmental factors and
      mechanisms. Nevertheless, relatively little attention has focused on the role of
      culture in shaping hallucinations. This article reviews the published research,
      drawing on the expertise of both anthropologists and psychologists. We argue that
      the extant body of work suggests that culture does indeed have a significant
      impact on the experience, understanding, and labeling of hallucinations and that
      there may be important theoretical and clinical consequences of that observation.
      We find that culture can affect what is identified as a hallucination, that there
      are different patterns of hallucination among the clinical and nonclinical
      populations, that hallucinations are often culturally meaningful, that
      hallucinations occur at different rates in different settings; that culture
      affects the meaning and characteristics of hallucinations associated with
      psychosis, and that the cultural variations of psychotic hallucinations may have
      implications for the clinical outcome of those who struggle with psychosis. We
      conclude that a clinician should never assume that the mere report of what seems
      to be a hallucination is necessarily a symptom of pathology and that the
      patient's cultural background needs to be taken into account when assessing and
      treating hallucinations.

PMID- 24936084
TI  - Visual hallucinations in the psychosis spectrum and comparative information from
      neurodegenerative disorders and eye disease.
AB  - Much of the research on visual hallucinations (VHs) has been conducted in the
      context of eye disease and neurodegenerative conditions, but little is known
      about these phenomena in psychiatric and nonclinical populations. The purpose of
      this article is to bring together current knowledge regarding VHs in the
      psychosis phenotype and contrast this data with the literature drawn from
      neurodegenerative disorders and eye disease. The evidence challenges the
      traditional views that VHs are atypical or uncommon in psychosis. The weighted
      mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the
      general community. VHs are linked to a more severe psychopathological profile and
      less favorable outcome in psychosis and neurodegenerative conditions. VHs
      typically co-occur with auditory hallucinations, suggesting a common etiological
      cause. VHs in psychosis are also remarkably complex, negative in content, and are
      interpreted to have personal relevance. The cognitive mechanisms of VHs in
      psychosis have rarely been investigated, but existing studies point to source
      monitoring deficits and distortions in top-down mechanisms, although evidence for
      visual processing deficits, which feature strongly in the organic literature, is
      lacking. Brain imaging studies point to the activation of visual cortex during
      hallucinations on a background of structural and connectivity changes within
      wider brain networks. The relationship between VHs in psychosis, eye disease, and
      neurodegeneration remains unclear, although the pattern of similarities and
      differences described in this review suggests that comparative studies may have
      potentially important clinical and theoretical implications.

PMID- 24936083
TI  - From phenomenology to neurophysiological understanding of hallucinations in
      children and adolescents.
AB  - Typically reported as vivid, multisensory experiences which may spontaneously
      resolve, hallucinations are present at high rates during childhood. The risk of
      associated psychopathology is a major cause of concern. On the one hand, the risk
      of developing further delusional ideation has been shown to be reduced by better
      theory of mind skills. On the other hand, ideas of reference, passivity
      phenomena, and misidentification syndrome have been shown to increase the risk of
      self-injury or heteroaggressive behaviors. Cognitive psychology and brain-imaging
      studies have advanced our knowledge of the mechanisms underlying these early
      onset hallucinations. Notably, specific functional impairments have been
      associated with certain phenomenological characteristics of hallucinations in
      youths, including intrusiveness and the sense of reality. In this review, we
      provide an update of associated epidemiological and phenomenological factors
      (including sociocultural context, social adversity, and genetics, considered in
      relation to the psychosis continuum hypothesis), cognitive models, and
      neurophysiological findings concerning hallucinations in children and
      adolescents. Key issues that have interfered with progress are considered and
      recommendations for future studies are provided. 

PMID- 24936085
TI  - Auditory verbal hallucinations in persons with and without a need for care.
AB  - Auditory verbal hallucinations (AVH) are complex experiences that occur in the
      context of various clinical disorders. AVH also occur in individuals from the
      general population who have no identifiable psychiatric or neurological
      diagnoses. This article reviews research on AVH in nonclinical individuals and
      provides a cross-disciplinary view of the clinical relevance of these experiences
      in defining the risk of mental illness and need for care. Prevalence rates of AVH
      vary according to measurement tool and indicate a continuum of experience in the
      general population. Cross-sectional comparisons of individuals with AVH with and
      without need for care reveal similarities in phenomenology and some underlying
      mechanisms but also highlight key differences in emotional valence of AVH,
      appraisals, and behavioral response. Longitudinal studies suggest that AVH are an
      antecedent of clinical disorders when combined with negative emotional states,
      specific cognitive difficulties and poor coping, plus family history of
      psychosis, and environmental exposures such as childhood adversity. However,
      their predictive value for specific psychiatric disorders is not entirely clear.
      The theoretical and clinical implications of the reviewed findings are discussed,
      together with directions for future research.

PMID- 24936086
TI  - Symptom dimensions of the psychotic symptom rating scales in psychosis: a
      multisite study.
AB  - The Psychotic Symptom Rating Scales (PSYRATS) is an instrument designed to
      quantify the severity of delusions and hallucinations and is typically used in
      research studies and clinical settings focusing on people with psychosis and
      schizophrenia. It is comprised of the auditory hallucinations (AHS) and delusions
      subscales (DS), but these subscales do not necessarily reflect the psychological
      constructs causing intercorrelation between clusters of scale items.
      Identification of these constructs is important in some clinical and research
      contexts because item clustering may be caused by underlying etiological
      processes of interest. Previous attempts to identify these constructs have
      produced conflicting results. In this study, we compiled PSYRATS data from 12
      sites in 7 countries, comprising 711 participants for AHS and 520 for DS. We
      compared previously proposed and novel models of underlying constructs using
      structural equation modeling. For the AHS, a novel 4-dimensional model provided
      the best fit, with latent variables labeled Distress (negative content, distress,
      and control), Frequency (frequency, duration, and disruption), Attribution
      (location and origin of voices), and Loudness (loudness item only). For the DS, a
      2-dimensional solution was confirmed, with latent variables labeled Distress
      (amount/intensity) and Frequency (preoccupation, conviction, and disruption). The
      within-AHS and within-DS dimension intercorrelations were higher than those
      between subscales, with the exception of the AHS and DS Distress dimensions,
      which produced a correlation that approached the range of the within-scale
      correlations. Recommendations are provided for integrating these underlying
      constructs into research and clinical applications of the PSYRATS.

PMID- 24936087
TI  - Better than mermaids and stray dogs? Subtyping auditory verbal hallucinations and
      its implications for research and practice.
AB  - The phenomenological diversity of auditory verbal hallucinations (AVH) is not
      currently accounted for by any model based around a single mechanism. This has
      led to the proposal that there may be distinct AVH subtypes, which each possess
      unique (as well as shared) underpinning mechanisms. This could have important
      implications both for research design and clinical interventions because
      different subtypes may be responsive to different types of treatment. This
      article explores how AVH subtypes may be identified at the levels of
      phenomenology, cognition, neurology, etiology, treatment response, diagnosis, and
      voice hearer's own interpretations. Five subtypes are proposed; hypervigilance,
      autobiographical memory (subdivided into dissociative and nondissociative), inner
      speech (subdivided into obsessional, own thought, and novel), epileptic and
      deafferentation. We suggest other facets of AVH, including negative content and
      form (eg, commands), may be best treated as dimensional constructs that vary
      across subtypes. After considering the limitations and challenges of AVH
      subtyping, we highlight future research directions, including the need for a
      subtype assessment tool.

PMID- 24936088
TI  - Emerging perspectives from the hearing voices movement: implications for research
      and practice.
AB  - The international Hearing Voices Movement (HVM) is a prominent mental health
      service-user/survivor movement that promotes the needs and perspectives of
      experts by experience in the phenomenon of hearing voices (auditory verbal
      hallucinations). The main tenet of the HVM is the notion that hearing voices is a
      meaningful human experience, and in this article, we discuss the historical
      growth and influence of the HVM before considering the implications of its values
      for research and practice in relation to voice-hearing. Among other
      recommendations, we suggest that the involvement of voice-hearers in research and
      a greater use of narrative and qualitative approaches are essential. Challenges
      for implementing user-led research are identified, and avenues for future
      developments are discussed.

PMID- 24936091
TI  - A novel deletion in the iron-response element of the L-ferritin gene, causing
      hyperferritinaemia cataract syndrome.
AB  - A 47-year-old woman, presenting to her family physician with fatigue, was
      incidentally found to have persistently elevated ferritin. There was clinically
      no suggestion of iron overload, and laboratory testing showed transferrin
      saturation at the low end of the reference range. After ruling out acquired
      causes of hyperferritinaemia, as well as laboratory interference, further
      questioning revealed a history of bilateral early-onset cataracts, allowing a
      diagnosis of hyperferritinaemia cataract syndrome to be made. DNA sequencing of
      the 5' untranslated region of the L-ferritin gene revealed a novel 4-base
      deletion in the iron response element, within a region known to be crucial for
      binding iron regulatory protein. 

PMID- 24936092
TI  - Risk and benefit of dual antiplatelet treatment among non-revascularized
      myocardial infarction patients in different age groups.
AB  - BACKGROUND: Dual anti-platelet treatment with clopidogrel and aspirin is
      indicated for most patients after myocardial infarction. We examined the
      risk/benefit relationship of dual anti-platelet treatment according to age in a
      nationwide cohort of 30,532 myocardial infarction patients without
      revascularization. METHODS: Patients admitted with first-time myocardial
      infarction in 2002-2010, not undergoing revascularization, were identified from
      nationwide Danish registers. Dual anti-platelet treatment use was assessed by
      claimed prescriptions. Stratified into age groups, risk of bleeding, all-cause
      mortality and a combined endpoint of cardiovascular death, recurrent myocardial
      infarction and ischaemic stroke was analysed by Cox proportional-hazard models
      and tested in a propensity-score matched population. RESULTS: A total of 21,302
      users and 9230 non-users of dual anti-platelet treatment were included (mean age
      67.02 (+/-13.8) years and 64.7% males). Use of dual anti-platelet treatment
      decreased with age: 80% (<60 years), 76% (60-69 years), 66% (70-79 years) and 52%
      (>79 years). We found a reduced risk of cardiovascular death, recurrent
      myocardial infarction and ischaemic stroke in users <60 years (Hazard ratio (HR)
      =0.69; 95% confidence interval (CI) 0.59-0.80), 60-69 years (HR=0.64; 95% CI 0.56
      0.73), 70-79 years (HR=0.80; 95% CI 0.72-0.89) and >79 years (HR=0.92; 95% CI
      0.84-1.01, NS). Risk of bleeding increased with dual anti-platelet treatment use
      in patients aged <60 years (HR=1.63; 95% CI 1.17-2.26), 60-69 years (HR=1.22; 95%
      CI 0.97-1.59, NS), 70-79 years (HR=1.42; 95% CI 1.17-1.72) and >79 years
      (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found
      in the propensity-matched population. CONCLUSION: Dual anti-platelet treatment
      use was less likely among elderly patients although similar effects regarding
      both risk and benefit were found in all age groups. Increased focus on initiating
      dual anti-platelet treatment in elderly, non-invasively treated myocardial
      infarction patients is warranted.

PMID- 24936090
TI  - The clinical and cost-effectiveness of brief advice for excessive alcohol
      consumption among people attending sexual health clinics: a randomised controlled
      trial.
AB  - OBJECTIVES: To examine the clinical and cost-effectiveness of brief advice for
      excessive alcohol consumption among people who attend sexual health clinics.
      METHODS: Two-arm, parallel group, assessor blind, pragmatic, randomised
      controlled trial. 802 people aged 19 years or over who attended one of three
      sexual health clinics and were drinking excessively were randomised to either
      brief advice or control treatment. Brief advice consisted of feedback on alcohol
      and health, written information and an offer of an appointment with an Alcohol
      Health Worker. Control participants received a leaflet on health and lifestyle.
      The primary outcome was mean weekly alcohol consumption during the previous 90
      days measured 6 months after randomisation. The main secondary outcome was
      unprotected sex during this period. RESULTS: Among the 402 randomised to brief
      advice, 397 (99%) received it. The adjusted mean difference in alcohol
      consumption at 6 months was -2.33 units per week (95% CI -4.69 to 0.03, p=0.053)
      among those in the active compared to the control arm of the trial. Unprotected
      sex was reported by 154 (53%) of those who received brief advice, and 178 (59%)
      controls (adjusted OR=0.89, 95% CI 0.63 to 1.25, p=0.496). There were no
      significant differences in costs between study groups at 6 months. CONCLUSIONS:
      Introduction of universal screening and brief advice for excessive alcohol use
      among people attending sexual health clinics does not result in clinically
      important reductions in alcohol consumption or provide a cost-effective use of
      resources. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN 99963322.

PMID- 24936093
TI  - Autologous Fat Transfer: The Progenitor Cell Response to Different Recipient
      Environments.
AB  - BACKGROUND: Autologous fat transfer is a common procedure; however, results are
      variable and unpredictable. OBJECTIVES: Stem cell responses to hypoxic
      environments need to be elucidated to determine which cell types contribute to
      graft survival. METHODS: Acellular dermal matrix (ADM) envelopes were implanted
      in the subcutaneous tissues of 4 swine. In each swine, 2 envelopes were inserted
      as controls (ADM group), and 2 were placed and injected with 5 mL of autologous
      fat (ADM/fat group). Two additional envelopes were inserted and filled with 5 mL
      of fat and an omental pedicle (A/F/O group). Animals were sacrificed and the
      envelopes excised at 1, 2, 4, and 16 weeks. Specimens were analyzed
      histologically and/or with flow cytometry. RESULTS: Fat was retained in ADM
      envelopes with and without a pedicle blood supply, although the percentage of
      volume retention was greater in the pedicled group. The peak number of
      mesenchymal progenitor cells within the ADM/fat group was significantly greater
      than the peak in the A/F/O group (P =.044), whereas endothelial progenitor cells
      in the ADM/fat group showed a prolonged increase through 4 weeks (P =.015 vs the
      A/F/O group at week 4). At 16 weeks, the interior surface of the matrix in the
      ADM/fat group had significantly more blood vessels than that of the ADM or A/F/O
      group (P = .0021 and .0036, respectively). CONCLUSIONS: Injecting fat into
      hypoxic environments significantly increases the mesenchymal and endothelial
      progenitor cell responses and enhances the formation of blood vessels.

PMID- 24936095
TI  - An adjuvant technique using a drape and button in eyelid surgery.

PMID- 24936089
TI  - From tones in tinnitus to sensed social interaction in schizophrenia: how
      understanding cortical organization can inform the study of hallucinations and
      psychosis.
AB  - The content, modality, and perceptual attributes of hallucinations and other
      psychotic symptoms may be related to neural representation at a single cell and
      population level in the cerebral cortex. A brief survey of some principles and
      examples of cortical representation and organization will be presented together
      with evidence for a correspondence between the neurobiology of brain areas
      activated at the time of a hallucination and the content of the corresponding
      hallucinatory and psychotic experiences. Contrasting the hallucinations of
      schizophrenia with other conditions, we highlight phenomenological aspects of
      hallucinations that are ignored in clinical practice but carry potentially
      important information about the brain regions and dysfunctions underlying them.
      Knowledge of cortical representation and organization are being used to develop
      animal models of hallucination and to test treatments that are now beginning to
      translate to the clinical domain.

PMID- 24936094
TI  - Surface Aesthetics in Tip Rhinoplasty: A Step-by-Step Guide.
AB  - Tip rhinoplasty is a key component of aesthetic rhinoplasty. An understanding of
      the correlation between tip surface aesthetics and the underlying anatomic
      structures enables proper identification and correction of tip abnormalities.
      Surface aesthetics of the attractive nose are created by certain lines, shadows,
      and highlights with specific proportions and breakpoints. In this Featured
      Operative Technique, the authors describe a stepwise process for tip rhinoplasty
      that conceptualizes aesthetic subunits as geometric polygons to define the
      existing deformity, the operative plan, and the aesthetic goals. Tip rhinoplasty
      is described in detail, from initial markings through incisions and dissection.
      The autorim graft concept is explained, and lateral crural steal and footplate
      setback techniques are described for the attainment of symmetric domes with
      correct lateral crural resting angles. Methods in columellar reconstruction are
      described, including creating the columella (C') breakpoint and the infralobular
      caudal contour graft. The principal author (B.C.) has applied these techniques to
      257 consecutive "polygon rhinoplasties" over the past 3 years. 

PMID- 24936096
TI  - Facial aesthetic surgery in the setting of localized heat-induced urticaria.

PMID- 24936099
TI  - An Efficient Simulation Budget Allocation Method Incorporating Regression for
      Partitioned Domains.
AB  - Simulation can be a very powerful tool to help decision making in many
      applications but exploring multiple courses of actions can be time consuming.
      Numerous ranking & selection (R&S) procedures have been developed to enhance the
      simulation efficiency of finding the best design. To further improve efficiency,
      one approach is to incorporate information from across the domain into a
      regression equation. However, the use of a regression metamodel also inherits
      some typical assumptions from most regression approaches, such as the assumption
      of an underlying quadratic function and the simulation noise is homogeneous
      across the domain of interest. To extend the limitation while retaining the
      efficiency benefit, we propose to partition the domain of interest such that in
      each partition the mean of the underlying function is approximately quadratic.
      Our new method provides approximately optimal rules for between and within
      partitions that determine the number of samples allocated to each design
      location. The goal is to maximize the probability of correctly selecting the best
      design. Numerical experiments demonstrate that our new approach can dramatically
      enhance efficiency over existing efficient R&S methods.

PMID- 24936097
TI  - Internal and external carotid artery embolism following facial injection of
      autologous fat.
AB  - Autologous fat injection is a common aesthetic procedure for soft-tissue
      augmentation of the face. Although this procedure is generally regarded as safe,
      several patients have experienced acute visual loss or cerebral infarction after
      these injections. We describe a case of internal and external carotid artery fat
      embolism that occurred following injection of autologous fat into the face. It
      appeared that the injected fat entered a branch of the left external carotid
      artery and that the embolus likely migrated into the left internal carotid artery
      and distally into the left ophthalmic artery, left anterior artery, and middle
      cerebral artery. LEVEL OF EVIDENCE 5: 

PMID- 24936098
TI  - Does Tramadol Have a Role in Pain Control in Palliative Care?
AB  - BACKGROUND: The effectiveness of the step II of the World Health Organization
      analgesic ladder including tramadol has been questioned recently. METHODS:
      Retrospective study of patients treated with tramadol admitted as inpatients to
      one palliative care unit between November 1, 2009, and October 30, 2012. RESULTS:
      In the study period, 730 patients were admitted and 66 (9%) of them met the
      criteria for inclusion; 45 (68%) continued medication with tramadol until
      discharge from the unit, while 21 (32%) had to switch to an opioid for moderate
      to severe pain. The reason for switching was uncontrolled pain in 16 (76%)
      patients, and for 5 (24%) patients, the switch was made for other reasons.
      CONCLUSION: The data suggest that tramadol may have a role to play in the
      treatment of pain in palliative care.

PMID- 24936100
TI  - Effects of six-week clarithromycin therapy in corticosteroid-dependent asthma: A
      randomized, double-blind, placebo-controlled pilot study.
AB  - BACKGROUND: Although corticosteroids such as prednisone are efficacious for the
      treatment of severe asthma, chronic administration of oral corticosteroid therapy
      is associated with significant adverse effects. Previous studies have shown that
      clarithromycin is effective in reducing bronchial hyperresponsiveness and
      allergen-induced bronchoconstriction. However, the effect of long-term
      clarithromycin therapy in patients with prednisone-dependent asthma is uncertain.
      OBJECTIVE: This study was conducted to determine the effects of oral
      clarithromycin on prednisone daily dosage, pulmonary function, quality of life
      (QOL), and asthmatic symptoms in patients with corticosteroid-dependent asthma.
      METHODS: This 14-week, prospective, randomized, double-blind, placebo-controlled
      pilot study was conducted at Pulmonary Associates (Phoenix, Arizona) and the
      University of Illinois at Chicago Medical Center (Chicago, Illinois). Patients
      aged 18 to 75 years with an established diagnosis of asthma and who had been
      receiving >=5 mg/d of prednisone for the preceding 6 months were enrolled. After
      a 4-week data-collection period, patients received clarithromycin 500 mg BID for
      6 weeks, followed by a 4-week follow-up period. The effects of clarithromycin
      therapy on prednisone dosage requirements, pulmonary function (as assessed using
      spirometry), QOL, and asthmatic symptoms (nocturnal asthma, shortness of breath,
      chest discomfort, wheezing, and cough) were assessed. RESULTS: Fourteen patients
      (9 men, 5 women; mean [SD] age, 62 [13] years) completed the study and were
      included in the final analysis. One patient withdrew from the study due to
      clarithromycin-related nausea. After 6 weeks of clarithromycin therapy, patients
      were able to tolerate a significant reduction in mean (SD) prednisone dosage from
      baseline (30% [18%]; P- 0.020). Pulmonary function, QOL, and asthmatic symptoms
      did not significantly worsen despite reduction in prednisone dose. All patients
      who completed the study tolerated clarithromycin therapy. CONCLUSIONS: In this
      pilot study of patients with corticosteroid-dependent asthma, 6-week
      clarithromycin 500 mg BID was clinically effective in allowing a reduction in
      prednisone dosage, without worsening pulmonary function, QOL, or asthmatic
      symptoms. In addition, clarithromycin was well tolerated, with only 1 patient
      discontinuing therapy due to treatment-related nausea.

PMID- 24936101
TI  - Effects and cost of glycyrrhizin in the treatment of upper respiratory tract
      infections in members of the Japanese maritime self-defense force: Preliminary
      report of a prospective, randomized, double-blind, controlled, parallel-group,
      alternate-day treatment assignment clinical trial.
AB  - BACKGROUND: Upper respiratory tract infections (URTIs) account for at least half
      of all acute illnesses. Specific antiviral therapy has not been developed against
      most respiratory viruses thought to cause URTIs. The pharmacologic action of
      glycyrrhizin has been shown to produce anti-inflammatory activity, modulation of
      the immune system, inhibition of virus growth, and inactivation of viruses.
      OBJECTIVE: The aim of this study was to assess the tolerability, efficacy, and
      cost of glycyrrhizin in improving the severity and duration of signs and symptoms
      of URTIs. The primary end point was tolerability, and the secondary and points
      included improvement in signs and symptoms of URTI and cost. METHODS: Members of
      the Japanese Maritime Self-Defense Force (SDF) treated for URTIs from January
      2002 to May 2002 in the SDF Etajima Hospital (Hiroshima, Japan) were eligible for
      this prospective, randomized, double-blind, controlled, parallel-group, alternate
      day treatment assignment study. All patients in this study fulfilled the
      following enrollment criteria: admitted to the hospital on the first arrival day
      as an outpatient; fever (body temperature <38.0 degrees C) with signs and
      symptoms of URTI (headache, sore throat, rhinorrhea, pharyngitis); and had not
      received antibiotics or oseltamivir phosphate for 4 weeks before the study.
      Patients who were admitted on an even day received an IV drip infusion of 40 mL
      of glycyrrhizin (0.2%) and 500 mL of lactated Ringer's solution daily during
      hospitalization (glycyrrhizin group). Patients who were admitted on an odd day
      received an IV drip infusion of 500 mL/d of lactated Ringer's solution only
      (control group). Adverse effects were assessed by the physicians during
      hospitalization, using patient interview and laboratory analysis. RESULTS: Forty
      one consecutive patients entered the study; 15 patients (15 men, 0 women; mean
      [SD] age, 25.2 [1.5] years) were assigned to the glycyrrhizin group and 269
      patients (24 men, 2 women; mean [SD] age, 22.6 [0.9] years) were assigned to the
      control group. The 2 groups were similar in terms of baseline characteristics.
      The mean duration of hospitalization was shorter (P = 0.01), the mean maximum
      body temperature 24 to 48 hours after admission was less (P = 0.05), and the cost
      of therapy (P = 0.03) was less in the glycyrrhizin group than the control group.
      No AEs were reported. CONCLUSIONS: In this study of hospitalized patients with
      URTIs, glycyrrhizin therapy was associated with a shorter hospitalization, lower
      grade fever, and lower cost of therapy compared with controls, showing that it
      may be beneficial to patients with URTIs without acute bacterial infections.

PMID- 24936102
TI  - Bioequivalence study of two formulations of enalapril, at a single oral dose of
      20 mg (tablets): A randomized, two-way, open-label, crossover study in healthy
      volunteers.
AB  - BACKGROUND: Enalapril maleate is the monoethyl ester prodrug of enalapril- at, an
      angiotensin-converting enzyme inhibitor indicated in the management of essential
      and renovascular hypertension, and in the treatment of congestive heart failure
      and in asymptomatic patients with left ventricular dysfunction and an ejection
      fraction of >=35%. Enalapril has little pharmacologic activity until hydrolyzed
      in vivo to enalaprilat. OBJECTIVE: The aim of the present study was to compare
      the bioavailability and tolerability of 2 commercial brands (test and reference
      formulations) of enalapril tablets (20 mg), described as the rate and extent of
      absorption of the active moiety, to assess their bioequivalence. METHODS: This
      single-dose, randomized, 2-way, open-label, crossover study in healthy volunteers
      aged 18 to 40 years was conducted at the Clinical Pharmacology Study Unit,
      Hospital Clinico San Carlos (Madrid, Spain). Subjects were randomized to receive
      (under fasting conditions) either the test or reference formulation of enalapril
      (20-mg tablet) at study period 1 and the opposite formulation at study period 2.
      Study periods were separated by a washout period of at least 7 days. During each
      study period, 15 plasma extractions were made to determine enalapril and
      enalaprilat plasma concentrations and to calculate the pharmacokinetic (PK)
      properties (maximal plasma drug concentration [Cmax], time to Cmax [Tmax], area
      under the plasma concentration-time curve [AUC] to the last measurable
      concentration [AUCt], AUC from time 0 to infinity [AUC0-infinity], mean residence
      time, and elimination half-life [tl2]) of both. Physical examination, subject
      interview, laboratory analyses, electrocardiogram, and blood pressure (BP) were
      used to assess tolerability. RESULTS: Twenty-four subjects were included in the
      study (12 men, 12 women; mean [SD] age, 22.8 [2.2] years [range, 19-30 years]).
      Of these, 1 subject (4.2%) withdrew from the study for personal reasons; thus, PK
      and statistical analyses included results from 23 subjects. No statistically
      significant sequence or period effect was found. Tmax was not statistically
      different between the 2 formulations, and the 90% CI calculated for Tmax for the
      difference of the medians was within the predefined range. The 90% CIs of the
      logarithmically transformed concentration-derived parameters (Cmax AUCt, and AUC0
      infinity) also were within the predefined range; thus, the 2 formulations are
      considered bioequivalent. For both formulations, systolic and diastolic BPs
      showed significant reductions compared with baseline values (P < 0.05). Seven
      adverse effects were recorded, all of them transient and none of severe
      intensity. CONCLUSIONS: In this study of 2 commercial brands (test and reference
      formulations) of enalapril in healthy subjects, designed and conducted under Good
      Clinical Practice guidelines, a similar rate and extent of absorption for both
      formulations were found to be bioequivalent. Both formulations produced a
      significant decrease in BP values and were generally well tolerated.

PMID- 24936103
TI  - A comparison of the tolerability of two dilution volumes (0.5 mL and 1.0 mL) of a
      purified chick embryo cell rabies vaccine administered intramuscularly to healthy
      adult volunteers: A randomized, intraindividual, assessor-blind study.
AB  - BACKGROUND: The current recommendation of the manufacturer for administering
      purified chick embryo cell rabies vaccine (PCECV) is to reconstitute the contents
      with 1.0 mL of water for injection (WFI). However, it has been debated whether a
      lower volume of WFI (0.5 mL) is likely to cause less pain. OBJECTIVES: The aims
      of this study were to compare the tolerability of PCECV administered IM at a
      volume of 0.5 mL versus 1.0 mL of diluent and to determine the immunogenicity of
      the vaccine when administered according to the World Health Organization
      recommended preexposure prophylaxis regimen for rabies immunization. METHODS:
      This comparative, intraindividual, assessor-blind study was conducted at the
      Department of Clinical Pharmacology, Topiwala National Medical College and Bai
      Yamunabai Laxman Nair Charitable Hospital Mumbai, India). Healthy volunteers aged
      18 to 50 years received, by randomized sequence, 3 IM injections of PCECV,
      diluted in 0.5 mL or 1.0 mL of WFI, on study days 0, 7, and 28. Tolerability was
      assessed at 30 minutes and 24 hours after injection and included assessments for
      local and systemic reactions. For immunogenicity assessment, rabies virus
      neutralizing antibody 0RVNA) titers were assayed at baseline and on day 49 (ie, 3
      weeks after the third injection). RESULTS: Twenty-six subjects (24 men, 2 women;
      mean [SD] age, 22.4 [2.4] years; mean [SD] body weight, 59.0 [11.3] kg) entered
      the study. Twenty-five subjects were included in the tolerability assessment; 24
      in the immunogenicity assessment. No statistically significant differences were
      found between dilutions in the frequency of local and systemic reactions. Most
      reactions were mild. All subjects developed RVNA titers >0.5 IU/mL (indicative of
      protection) by day 49. CONCLUSIONS: In this population of healthy volunteers, a
      full antigenic dose of PCECV in a dilution of 0.5 mL WFI is as well tolerated
      locally and systemically as in a dilution of 1.0 mL. All subjects developed
      levels of RVNA far exceeding 0.5 IU/mL, which is indicative of protection against
      rabies.

PMID- 24936104
TI  - Efficacy and tolerability of olanzapine in patients with schizophrenia in
      lithuania: A 13-week, multicenter, open-label, nonrandomized study.
AB  - BACKGROUND: The atypical antipsychotic olanzapine has been approved for the
      treatment of schizophrenia in Europe since 1996 but has been used primarily as a
      second-line treatment to the less expensive typical agents. However, similar to
      other atypical antipsychotic drugs, olanzapine has a lower risk of inducing
      extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, and
      sexual dysfunction compared with the typical antipsychotic drugs. OBJECTIVE: The
      aim of this study was to determine whether patients with schizophrenia who have a
      poor response to their present antipsychotic therapy would show improvement when
      switched to olanzapine. METHODS: This 13-week, multicenter, open-label,
      nonrandomized trial was conducted at 5 centers in Lithuania. Patients were
      started on oral olanzapine 10-mg tablets once daily, which could be adjusted by 5
      mg/d in the dosing range of 5 to 20 mg/d. The primary efficacy measure was the
      total score on the Brief Psychiatric Rating Scale (BPRS), which was extracted
      from the Positive and Negative Syndrome Scale (PANSS). Efficacy response rate was
      defined a priori as the percentage of patients achieving >=40% improvement in the
      BPRS total score. Secondary assessments included the PANSS total and BPRS and
      PANSS subscales and scores on the Clinical Global Impression-Severity of Illness
      (CGI-S), the CGI-Global Improvement (CGI-I), and the Patient Global Impression
      Improvement (PGI-I) tests. Tolerability was primarily measured by assessing the
      incidence of treatment-emergent adverse events (AEs) according to the Udvalg fuer
      Kliniske Undersogelser (UKU) Side Effect Rating Scale and laboratory analyses.
      RESULTS: Twenty-four patients (13 men [54.2%]; mean [SD] age, 32.4 [8.1] years)
      entered the study. Twenty-three (95.8%) of the 24 patients completed the study.
      The mean (SD) daily dosage of olanzapine was 11.40 (2.18) mg/d. The total mean
      (SD) BPRS score improved significantly from 37.8 (7.9) to 19.5 (13.7) (P <
      0.001). The response rate was 58.3% (14/24 patients). The mean positive and
      negative BPRS scores and the mean total and subscale PANSS scores all improved
      significantly from baseline (P < 0.001). The mean (SD) CGI-S score improved
      significantly from 4.8 (0.8) at baseline to 3.5 (1.1) at end point (P < 0.001).
      Twenty-two patients (91.7%) showed improvement on the CGM scale. Similar
      improvement was found on the PGM scale. Treatment-emergent AEs occurred in 7
      patients (29.2%). Improvement was found on 31 of the 48 UKU scale items; no
      change was shown on 15 items; and slight worsening was shown on 2 items. No
      clinical abnormalities were detected during the study. CONCLUSION: In this study
      of Lithuanian patients with schizophrenia, significant improvement was shown in
      all efficacy measures. In addition, olanzapine was well tolerated in these
      patients.

PMID- 24936107
TI  - Herpes simplex pneumonia: Combination therapy with oral acyclovir and aerosolized
      ribavirin in an immunocompetent patient.
AB  - BACKGROUND: Herpes simplex viruses (HSVs) are known to cause respiratory tract
      infections in immunocompromised hosts and, in rare instances, in immunocompetent
      hosts. Numerous in vitro and in vivo studies have shown that aerosolized
      administration of ribavirin can potently and selectively inhibit viral
      replication in pulmonary disease, thereby increasing the effectiveness of
      acyclovir in HSV. OBJECTIVE: In this case study, we reported on a 46-year-old
      immunocompetent woman with HSV type 1 pneumonia with bilateral pulmonary
      infiltrates but without mucocutaneous lesions. METHODS: The diagnosis was
      confirmed using cytology, viral culture, and serology. Because of the persistence
      of fever and dyspnea, we chose an antiviral therapy. The patient received oral
      acyclovir and aerosolized ribavirin to improve the antiviral effectiveness of the
      acyclovir and to reduce the symptoms and the time to resolution of the pulmonary
      disease. RESULTS: After 3 days of therapy, dyspnea and fever decreased and
      hypoxemia improved. After 2 weeks, computed tomography showed complete resolution
      of pulmonary abnormalities. The patient did not report any adverse effects.
      CONCLUSIONS: In our case study, we demonstrated that therapy with a combination
      of aerosolized ribavirin and oral acyclovir may be useful to reduce the severity
      of viral infection, the adverse effects, and the days of hospitalization. To our
      knowledge, this is the first report in the literature of the synergistic effects
      of the combination of aerosolized ribavirin and oral acyclovir in the treatment
      of an immunocompetent patient with HSV pneumonia.

PMID- 24936106
TI  - Effects of rosiglitazone treatment on the pentose phosphate pathway and
      glutathione-dependent enzymes in liver and kidney of rats fed a high-fat diet.
AB  - BACKGROUND: Animals fed high-fat diets have been shown to develop hyperglycemia,
      insulin resistance, hyperlipidemia, and moderate obesity, which resemble the
      human metabolic syndrome. Obesity, the metabolic syndrome, and some
      thiazolidinediones, which act as insulin sensitizers, may increase oxidative
      stress, and/or influence the levels of cellular reducing equivalents and
      homeostasis. OBJECTIVE: This study investigated the effects of a high-fat diet,
      rosiglitazone, or a high-fat diet plus rosiglitazone on metabolic syndrome
      parameters and crucial liver and kidney enzyme activities in rats. METHODS: Male
      Wistar rats were assigned to 4 groups (n = 6 per group): (1) the fat (F) group
      was fed a rodent diet comprising 45 kcal% fat, (2) the rosiglitazone (R) group
      was fed a standard rat chow comprising 4.97 kcal% fat plus rosiglitazone (3
      mg/kg.d), (3) the fat + rosiglitazone (FR) group was fed a rodent diet comprising
      45 kcal% fat (as lard, product D12451) plus rosiglitazone (3 mg/kg.d), and (4)
      the control (C) group was fed a standard rat chow comprising 4.97 kcal% fat.
      Animals were housed for 4 weeks, at which time the liver and kidney were isolated
      for spectrophotometric determination of enzyme activities. Body weight was
      measured before treatment (baseline) and then weekly throughout the study.
      Adiposity was measured at the end of the 4 weeks. RESULTS: The activities of
      glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6
      PGD), glutathione reductase (GR), and glutathione-S-transferase (GST) were
      significantly reduced in the livers of groups F, R, and FR compared with group C
      (all P < 0.05). Kidney G6PD, 6-PGD, and GR were found to be significantly lower
      in group R compared with the other groups (all P < 0.05). Kidney GST was similar
      in all groups. Plasma glucose, triglyceride, and insulin concentrations were
      significantly higher than in group F versus the other groups (all P < 0.05).
      Adiposity was increased in groups F and FR compared with groups C and R (all P <
      0.05). Serum cholesterol concentrations were similar in all groups. CONCLUSIONS:
      In this study, high-fat diet in rats decreased the enzyme activities responsible
      for pentose phosphate pathway and glutathione-dependent metabolism in liver but
      not in kidney. Similarly, these enzyme activities were inhibited with
      rosiglitazone treatment alone in both organs.

PMID- 24936105
TI  - Prophylactic activity of increasing doses of intravenous histamine in refractory
      migraine: Retrospective observations of a series of patients with migraine
      without aura.
AB  - BACKGROUND: Histamine is thought to play a pivotal role in the modulation of
      peripheral and central pain. The administration of increasing doses of histamine
      may lead to desensitization of receptors of histamine types 1 and 2, causing
      meningeal vasodilation, and to depletion of neuropeptides in the trigeminal
      ganglion, thus inhibiting the initiation of migraine. OBJECTIVE: In this study,
      the efficacy and tolerability of increasing doses of IV histamine in migraine
      prophylaxis were investigated. METHODS: This single-center, open-label,
      retrospective, controlled study was conducted at the Headache Center (Department
      of Internal Medicine, University of Florence, Villa Monna Tessa, Italy). Patients
      included in the study had 3 to 6 migraines without aura per month that were
      refractory to common symptomatic and prophylactic agents in the 6 months
      preceding the study. Patients were treated with IV histamine hydrochloride for 21
      days starting with a dosage of 0.5 mg/d and increasing to 4.0 mg/d. To assess the
      efficacy of the treatment, these patients were matched for age; sex; and
      frequency, duration, and severity of attacks with untreated migraineurs. Clinical
      benefit was defined as ? 1 migraine of mild intensity per month. Tolerability was
      assessed during the hospitalization period, and patients were instructed to
      contact the Headache Center to report any adverse effects after hospital
      discharge. RESULTS: The histamine group comprised 47 patients (40 women, 7 men;
      mean [SD] age, 42.0 [8.6] years) and the control group comprised 23 patients (20
      women, 3 men; mean [SD] age, 38.8 [8.4] years). The histamine-treated patients
      showed a clinical benefit lasting for a mean of 10.4 (4.2) months, while the
      patients in the control group showed a clinical benefit of 3.8 (1.9) months. The
      difference in the duration of the clinical benefit between the 2 groups was 6.6
      months (95% CI, 5.15-7.99). Adverse effects consisted of flushing, heat sensation
      during infusion, headache, and palpitations. CONCLUSIONS: In this study,
      histamine showed lasting prophylactic efficacy in migraineurs. If further
      research confirms this preliminary finding, histamine could be considered when
      established prophylactic drugs, such as betablockers, calcium antagonists,
      antidepressants, and antiepileptics, have not been effective.

PMID- 24936108
TI  - Pharmacokinetic properties and tolerability of single-dose terbutaline in
      patients with severe asthma treated in the pediatric intensive care unit.
AB  - BACKGROUND: Asthmatic children requiring treatment in the pediatric intensive
      care unit (PICU) receive aggressive drug therapy that may include IV
      administration of beta 2-receptor agonists to prevent progression to life
      threatening respiratory failure. The only pharmacologic agent in this class
      currently available for parenteral use in the United States is terbutaline. Study
      of IV dosing of terbutaline in the pediatric population has been limited.
      OBJECTIVE: The aim of this study was to determine the pharmacokinetic (PK)
      properties and tolerability of single-dose terbutaline in pediatric patients
      across a broad age range who were admitted to the PICU and were receiving maximal
      conventional asthma drug therapy. METHODS: This study was conducted at the PICU
      at Rainbow Babies and Children's Hospital (Cleveland, Ohio). Patients aged 6
      months to 16 years with severe exacerbation of reactive airways disease and who
      were undergoing maximal conventional therapy and had an arterial catheter were
      enrolled. Patients were arbitrarily assigned to receive a single IV infusion of 1
      of 3 doses of terbutaline (10, 20, or 30 MUg/kg), infused over 5 minutes. Blood
      samples were obtained for the determination of plasma terbutaline concentrations
      just before terbutaline was administered (baseline), immediately on completion of
      the IV infusion, and at 10, 20, and 40 minutes and 1, 2, 4, 8, 16, 32, 48, and 72
      hours after the 5-minute infusion. PK properties (elimination half-life [tl2],
      mean residence time [MRT], apparent steady-state volume of distribution [Vdss],
      and total body clearance [CI]) were determined and adverse effects were recorded.
      RESULTS: The determination of terbutaline PK properties was possible in 50 of 56
      enrolled patients (31 boys, 19 girls; mean [SD] age, 6.5 [4.5] years). The PK
      properties of terbutaline were linear over the dose range studied and, with the
      exception of the expected dose-dependent increases in peak terbutaline plasma
      concentration and area under the terbutaline plasma concentration-time curve, no
      statistically significant differences were observed in PK relative to dose.
      Therefore, we pooled the data for all subsequent analyses. Statistically
      significant correlations with patient age were observed with tl2 (r = 0.4, P <
      0.006), MRT (r = 0.4, P < 0.002), and Vdss (r = 0.33, P < 0.02), but not C1 (r = 
      0.03, P = NS). Single-dose terbutaline administration was generally well
      tolerated. CONCLUSIONS: Single-dose IV terbutaline was well tolerated in this
      study. In maximally treated asthmatic patients in the PICU, terbutaline
      elimination may be more rapid than in nonacutely ill children. These PK data
      suggest that if the drug is to be administered intravenously, the continuous IV
      infusion method, including loading doses for any subsequent dose escalations, may
      be the most appropriate. The influence of age and safety of long-term, continuous
      terbutaline IV infusion requires further study.

PMID- 24936109
TI  - Good work establishes the need for more research.

PMID- 24936110
TI  - Efficacy and tolerability of amifostine in elderly cancer patients.
AB  - BACKGROUND: Amifostine is a cytoprotective agent used to prevent cisplatin
      nephrotoxicity. It is associated with dose-limiting acute toxicities of emetic
      symptoms (nausea and vomiting) and transient hypotension. OBJECTIVE: The aim of
      this study was to analyze the efficacy and tolerability of amifostine in elderly
      cancer patients. METHODS: This 18-month, prospective, comparative study was
      conducted at the Department of Internal Medicine, Adnan Menderes University
      Hospital (Aydin, Turkey). Adult (aged 40-<85 years) hospitalized patients with
      advanced-stage cancer without comorbid diseases were enrolled. Patients were
      divided into 2 groups: age <70 years (group 1) and >=70 years (group 2). All
      patients were treated with amifostine + cisplatin-based chemotherapy (CT).
      Amifostine 910 mg/m(2) (maximum, 1500 mg) was administered as a 15-minute IV
      infusion. Clinical systolic and diastolic blood pressures (SBP and DBP,
      respectively) were measured at 0 minute (baseline), at 8 and 15 minutes of
      amifostine infusion, and at 30 minutes after the start of amifostine infusion. In
      addition to physical examination, chest radiography, electrocardiography, blood
      chemistry (including serum electrolytes and renal function tests), complete blood
      count, and complete urinalyses were performed before each CT administration and
      at the post-CT day of toxicity assessment. RESULTS: Thirty-five consecutive
      patients were enrolled (22 men, 13 women; mean [SD] age, 61 [12] years; group 1,
      n = 22; group 2, n = 13). Patients received a total of 153 CT cycles (median, 4
      cycles/patient; group 1, 96 cycles; group 2, 57 cycles). Amifostine caused
      significant SBP and DBP reductions at 8 minutes of infusion compared with
      baseline in groups 1 (both P < 0.001) and 2 (P = 0.002 and P = 0.006,
      respectively). Overall, 20 patients (57.1%) experienced >= 1 symptomatic
      hypotensive episode; these rates were not significantly different between groups
      1 (11 cases, 50.0%) and 2 (9 cases, 69.2%). Amifostine infusion was interrupted a
      similar number of times (6 times in group 1 and 4 times in group 2 [6.3% and 7.0%
      of administrations, respectively]) due to hypotension, but could be restarted in
      all. At 15 minutes, mean SBP and DBP values were not significantly different from
      baseline in either group. The mean baseline SBP values were similar between
      groups at baseline, and, overall, the differences in mean SBP and DBP values were
      not significant between groups at any time point. All other toxicities were
      comparable, and serum creatinine concentrations did not change significantly from
      baseline with CT in either group. CONCLUSIONS: In this study of the efficacy and
      tolerability of amifostine in elderly patients with advanced-stage cancer without
      comorbid diseases, amifostine was effective in reducing cisplatin-induced
      nephrotoxicity, with transient systolic and diastolic hypotension being the most
      prominent adverse effect. All other toxicities were either low grade or
      preventable. No significant differences in amifostine tolerability or toxicities
      were observed between the study groups.

PMID- 24936112
TI  - Effects of a weight-reduction program with orlistat on serum leptin levels in
      obese women: A 12-week, randomized, placebo-controlled study.
AB  - BACKGROUND: Leptin, which has been identified as an antiobesity hormone,
      regulates body weight by controlling food intake and energy expenditure via the
      hypothalamic-pituitary-gonadal axis. It appears that leptin may be an important
      factor in obesity management. Orlistat, a pancreatic lipase inhibitor, could
      reduce fat absorption and promote weight loss due to leptin metabolism.
      OBJECTIVE: The purpose of this study was to investigate the effects of orlistat
      therapy on serum leptin levels. METHODS: Obese women (body mass index [BMI], 30
      kg/m(2)) aged 18 to 50 years were randomly assigned to receive 12 weeks of oral
      treatment with diet-orlistat (120 mg TID) (DO group) or diet-placebo (DP group).
      During the treatment period, patients were asked to eat a balanced diet of -1200
      to 1600 kcal/d. Body composition was determined by bioelectrical impedance. Serum
      leptin levels were measured using radioimmunoassay at baseline and at study end.
      RESULTS: A total of 24 patients entered the study; 14 patients (mean [SE] BMI,
      37.7 [1.1] kg/m(2)) received orlistat and 10 patients (mean [SE] BMI, 39.4 [1.3]
      kg/m(2)) received placebo. Compared with baseline, mean percentages of loss of
      body weight and fat mass after 12 weeks of treatment were significant in the DO
      group (9.1% and 14.8%, respectively; both P = 0.001) and in the DP group (9.5%
      and 17.6%; both P = 0.005). The between-group differences were not statistically
      significant. Mean (SE) serum leptin levels also decreased significantly after
      treatment in the DO group (16.2 [1.2] vs 9.0 [1.0] ng/mL; P = 0.001) and in the
      DP group (19.3 [2.1] vs 9.7 [1.4] ng/mL; P = 0.005). The between-group difference
      was not statistically significant. CONCLUSIONS: In this study of obese women,
      orlistat treatment was associated with a similar decrease in body weight, fat
      mass, and serum leptin levels as placebo over a 12-week period. In this regard,
      short-term orlistat therapy may not provide an additional effect on serum leptin
      levels, and reduction in leptin levels were closely related to the decrease in
      fat mass.

PMID- 24936113
TI  - Efficacy and tolerability of a switch to fixed-dose combination therapy with
      amlodipine besylate/benazepril hydrochloride after monotherapy with amlodipine
      besylate: Data from the African-American subpopulation of a practice-based, open
      label study (the LOGIC study).
AB  - BACKGROUND: The LOGIC (LOtrel: Gauging Improved Control) study assessed the
      efficacy and tolerability of switching from amlodipine besylate monotherapy to
      fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride
      (HCI) in patients who were experiencing uncontrolled blood pressure (BP) or edema
      with monotherapy. OBJECTIVE: This article reports the efficacy and tolerability
      of amlodipine besylate/benazepril HCI combination therapy in the predefined
      African-American population of the LOGIC study. METHODS: This multicenter (1518
      centers across the United States), practice-based, open-label, clinical trial
      enrolled patients with mild to moderate essential hypertension. Patients in group
      1 had uncontrolled BP (sitting diastolic BP [DBP] >=90 mm Hg and <=110 mm Hg)
      during treatment with amlodipine besylate monotherapy 5 or 10 mg/d, and those in
      group 2 had controlled BP (sitting DBP ?90 mm Hg), but also had experienced edema
      during amlodipine besylate monotherapy. Participants were instructed to
      discontinue amlodipine besylate and were given amlodipine besylate/benazepril HCl
      5/10 mg/d or 5/20 mg/d for 4 weeks. For group 1, the primary efficacy outcome was
      the change in mean sitting DBP (MSDBP) from baseline to week 4; a secondary
      efficacy outcome was the change in mean sitting systolic BP (MSSBP) from baseline
      to week 4. The primary efficacy outcome for group 2 was the percentage of
      patients whose edema improved with the switch to combination therapy. The
      secondary efficacy variables in group 2 were the changes in MSDBP and MSSBP from
      baseline to week 4. Patients in groups 1 and 2 were questioned about any adverse
      events that may have occurred since the previous visit. At both study visits,
      medications were reviewed, and the level of edema was assessed. RESULTS: A total
      of 2055 African-American patients were enrolled in the study. At study end,
      African-American patients in group 1 (n = 1422 assessable patients) experienced
      significant reductions in MSSBP (13.9 mm Hg) and MSDBP (10.4 mm Hg) from those
      achieved during amlodipine besylate monotherapy (both P < 0.001). In group 2 (n =
      266 assessable patients), 81% of African-American patients reported improvement
      in edema, and BP remained well controlled. CONCLUSIONS: In this study of an
      African-American subpopulation of patients with mild to moderate essential
      hypertension who had uncontrolled BP while receiving amlodipine besylate
      monotherapy, switching from amlodipine besylate monotherapy to fixed-dose
      amlodipine besylate/benazepril HCl combination therapy reduced BP to a greater
      extent than with amlodipine besylate alone, and reduced the incidence of edema in
      patients who were edematous but who had controlled BP. Fixed-dose combination
      therapy with amlodipine besylate/benazepril HCI has the potential to improve BP
      control, leading to improved clinical outcomes and enhanced treatment compliance.

PMID- 24936114
TI  - Severity and impact of xerostomia in patients treated with botulinum toxin type b
      for cervical dystonia: Observations on the quality of life of patients with
      xerostomia.
AB  - BACKGROUND: Although dry mouth (xerostomia) has been reported with botulinum
      toxin type B used as treatment for cervical dystonia, the impact of this adverse
      effect (AE) on patients' activities of daily living (ADLs) has not been assessed.
      t OBJECTIVE: The aim of this study was to examine the severity, duration, and
      impact of xerostomia in patients with cervical dystonia who reported this AE in
      routine clinical practice following treatment with botulinum toxin type B.
      METHODS: In this uncontrolled study, investigators at 5 study centers across the
      United States retrospectively identified patients who were diagnosed with
      cervical dystonia and had received >= 1 treatment with botulinum toxin type B
      injection and who had reported xerostomia, based on patients' charts. These
      patients were mailed a survey that included questions about their treatment
      history, disease severity, and xerostomia (severity, onset, duration, change with
      subsequent injections, and effects on dental and oral health), as well as an 8
      item Patient Benefit Questionnaire (PBQ), which was designed to assess the impact
      of xerostomia symptoms on patients' ADLs. RESULTS: A total of 45 patients
      received a mean of 2.91 injections with botulinum toxin type B (mean dose per
      injection, 11,958 U), with a total of 131 injections. The mean severity of
      patient-rated xerostomia following the first injection of botulinum toxin type B
      was 3.88 on a scale of 1 (mild) to 5 (severe), and this rating did not change for
      patients who received subsequent injections (mean, 3.76). Following atypical
      injection of botulinum toxin type B, xerostomia began a mean (SD) of 4.82 (3.32)
      days later and persisted for a mean (SD) duration of 5.56 (3.57) weeks. The
      overall mean score on the 10-point PBQ prior to botulinum toxin treatment was
      8.89, which decreased to 5.42 following botulinum toxin type B injection (lower
      scores indicate more severe xerostomia). CONCLUSIONS: This study of patients with
      cervical dystonia suggests that patients who experience xerostomia following
      treatment with botulinum toxin type B injection, on average, rate their symptoms
      as moderate to severe and exhibit reduced scores on the PBQ-a questionnaire on
      which lower scores indicate greater negative impact of xerostomia on patients'
      ADLs.

PMID- 24936116
TI  - Pitfalls in crossover studies.

PMID- 24936115
TI  - Blood pressure control and weight loss in overweight or obese patients with
      previously treated or untreated mild to moderate hypertension given valsartan: An
      open-label study comparing pretreatment and posttreatment values.
AB  - BACKGROUND: Hypertension is associated with obesity. Recent studies have
      indicated that therapy with an angiotensin II antagonist, in addition to having
      an antihypertensive effect, may cause a reduction in body weight. OBJECTIVE: The
      aim of this study was to assess the efficacy and tolerability of valsartan in the
      treatment of overweight or obese patients with mild to moderate essential
      hypertension. METHODS: Overweight or obese outpatients aged 18 to <70 years with
      previously treated or untreated mild to moderate essential hypertension were
      eligible for this open-label study conducted at the Department of Internal
      Medicine and Aging, Clinica Medica II, Policlinico S. Orsola-Malpighi (Bologna,
      Italy). After a 1-week pharmacologic washout period, patients were treated with
      valsartan capsules at a fixed dosage of 80 mg once daily for 8 weeks. The dosage
      was increased to 160 mg once daily if, at 8 weeks, diastolic blood pressure (DBP)
      was not normalized; otherwise, the 80-mg/d dosage was maintained. Treatment was
      continued for an additional 16 weeks. Patients' heart rate, systolic blood
      pressure (SBP) and DBP, body mass index (BMI), and waist-hip ratio (WHR) were
      measured/calculated at baseline (week 0) and 8, 16, and 24 weeks. Patients were
      asked to maintain a 1600-kcal/d diet throughout the study. RESULTS: Forty-eight
      patients (28 men, 20 women; mean [SD] age, 57 [9] years) were included in the
      study. In the 45 patients (93.8%) who completed the study, mean SBP, DBP, and BMI
      were significantly decreased compared with baseline (all P < 0.001), but WHR was
      significantly increased (P < 0.05). After 24 weeks of treatment, 71.1 % of
      patients had SBP/DBP <= 140/<=90 mm Hg. Three patients (6.3%) withdrew from the
      study due to treatment-related adverse events. CONCLUSION: In this population of
      overweight or obese patients with mild to moderate hypertension, valsartan was
      well tolerated, and could be effective in controlling blood pressure and
      achieving weight loss in such patients.

PMID- 24936117
TI  - Effects of low-dose treatment with felodipine versus fosinopril in Chinese
      patients with nonischemic heart failure and normal blood pressure: A double
      blind, randomized, crossover study.
AB  - BACKGROUND: Two second-generation calcium channel blockers, felodipine and
      amlodipine besylate, have been associated with similar high mortality rates in
      patients with ischemic heart failure (HF) but not in patients with nonischemic
      causes of HF. In patients with nonischemic HF, amlodipine might have a beneficial
      effect on survival. However, no difference in mortality rates was found between
      felodipine and placebo in a nonischemic HF group. Felodipine 10 mg/d was used in
      1 large study, a dose considered high for nonischemic HF usually associated with
      normal blood pressure (BP). OBJECTIVE: The aim of this study was to compare the
      effects of 12-week, low-dose treatment with felodipine versus those of an
      angiotensin-converting enzyme inhibitor, fosinopril sodium, in patients with
      nonischemic HF and normal BP. METHODS: This double-blind, randomized, crossover
      trial was conducted at Taipei Medical University Hospital (Taipei, Taiwan).
      Patients aged >= 18 years with angiographically proved, nonischemic HF and normal
      BP who were being treated with an optimal regimen of digitalis and diuretics were
      enrolled. After a 2-week run-in period, patients were randomized to first receive
      12 weeks of treatment with felodipine tablets (2.5 mg/d) or fosinopril tablets
      (7.5 mg/d) and, after a 2-week washout period, were crossed over to the opposite
      treatment. Efficacy analysis was performed before (baseline) and after treatment
      and included symptomatic assessment using a 7-grade clinical scale; 2-dimensional
      echocardiography (2-D echo); exercise tests; and neurohumoral data, including
      plasma renin activity, plasma aldosterone, and 24-hour urinary epinephrine (E)
      and norepinephrine (NE) measurements. The primary end point was death due to HF,
      and the secondary end point was hospital admission due to worsening HF.
      Compliance was measured using a pill count at the end of each treatment period.
      RESULTS: We enrolled 33 patients. One developed worsening HF during the run-in
      period and was admitted. A total of 32 patients entered the study (18 men, 14
      women; mean [SD] age, 48.2 [6.3] years [range, 34-56 years]; mean [SD] systolic
      BP, 117.2 [9.8] mm Hg [range, 100-138 mm Hg]; mean [SD] diastolic BP, 59.4 [5.7]
      mm Hg [range, 50-72 mm Hg]). No hospital admission or cardiac death due to HF
      occurred during 12 weeks of treatment. Twenty-seven patients were included in the
      felodipine assessment, and 30 patients were included in the fosinopril
      assessment. Significant improvement in clinical score was noted in both treatment
      groups (both P < 0.01). The clinical scores did not differ significantly between
      the 2 treatments. No significant differences were found in 2-D echo parameters
      between treatments or within groups after treatment versus baseline. Significant
      improvement in exercise duration was noted with both study drugs after treatment
      versus baseline (both P < 0.01). No significant difference in exercise duration
      was found between the 2 treatments. Urinary E and NE were not significantly
      different between treatments or after treatment with either study drug compared
      with baseline. CONCLUSION: The present findings suggest that, in Chinese patients
      with moderate to severe HF who have normal BP and insignificant coronary artery
      disease and were being treated with diuretics and digitalis, a 12-week, low-dose
      course of felodipine (2.5 mg/d) as a vasodilator was associated with as
      satisfactory an outcome as standard treatment with fosinopril (7.5 mg/d).

PMID- 24936118
TI  - Effects of single-dose injectable paracetamolversus propacetamol in pain
      management after minor gynecologic surgery: A multicenter, randomized, double
      blind, active-controlled, two-parallel-group study.
AB  - BACKGROUND: Intravenous administration is the route of choice for drug therapy in
      the immediate postoperative period. Propacetamol (ProAPAP), an injectable prodrug
      of paracetamol requiring reconstitution, has demonstrated efficacy in managing
      acute pain and fever. However, it has been associated with pain at the injection
      site. A stable, ready-to-use formulation of paracetamol solution infused
      intravenously (IV-APAP) has been developed and might be associated with less pain
      at the injection site compared with ProAPAR. OBJECTIVE: The objective of this
      study was to assess the tolerability and efficacy of a single dose of IV APAP 1 g
      compared with those of a single dose of ProAPAP 2 g in patients with moderate to
      severe pain after minor gynecologic surgery. METHODS: This single-dose,
      randomized, double-blind, active-controlled,2-parallel-group study was conducted
      at 23 hospitals and outpatient clinics in France. After minor gynecologic
      surgery, patients reporting moderate to severe pain were randomized to receive a
      single 15-minute infusion of IV-APAP 1 g or ProAPAP 2 g (bioeyuivalent doses).
      Tolerability was monitored using local and systemic adverse event (AE) reporting,
      clinical examination including vital sign measurement, and patients' ratings of
      acceptability of the infusion. Efficacy end points included pain intensity at 0,
      1, 2, 4, and 6 hours; median time to rescue medication (defined as the time at
      which 50% of patients requested rescue medication); and percentage of patients
      requesting rescue medication. Patients' satisfaction with the study drugs was
      assessed using patient's global evaluation (PGE) and the percentage of patients
      willing to receive the treatment again. RESULTS: Of the 163 women who were
      randomized, 161 received the studymedication. The IV-APAP group comprised 80
      patients (mean [SD] age, 38.3 [12.8] years [range, 18.0-69.0 years]; mean [SD]
      weight, 61.1 [11.0] kg [range, 49.0-90.0 kg]), and the ProAPAP group comprised 81
      patients (mean [SD] age, 33.9 [12.0] years [range, 18.0-67.0 years]; mean [SD]
      weight, 61.6 [10.2] kg [range, 42.0-95.5 kg]); the difference in mean age between
      the 2 groups was statistically significant (P < 0.05). The incidence of local
      treatment-emergent AEs (TEAEs) was significantly lower in the IV-APAP group
      compared with that in the ProAPAP group (7.5% vs 38.3%; P < 0.001). No between
      group differences in the incidence of systemic TEAEs was found. All patients in
      the IV-APAP group found the infusion tolerable, compared with 95% of patients in
      the ProAPAP group. The median time to rescue medication was not evaluated because
      <50% of the patients in each group requested it. No significant differences in
      mean pain intensity score or percentage of patients requesting rescue medication
      were found between the 2 groups at any time point. The percentages of patients in
      the IV-APAP and ProAPAP groups who rated the study medication as good or
      excellent on the PGE (83.6% vs 75.6%; P < 0.05) and who were willing to receive
      the same treatment again (96.0% vs 81.0%; P = 0.005) were significantly higher
      with IV-APAP compared with ProAPAP. CONCLUSION: In these patients with moderate
      to severe pain after minor gynecologic surgery, a single dose of IV-APAP was
      associated with better local tolerability, similar analgesic efficacy, and
      greater patient satisfaction compared with a single bioequivalent dose of
      ProAPAP.

PMID- 24936119
TI  - Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high
      risk for cardiovascular disease in clinical practice: A randomized, open-label,
      parallel-group, multicenter study (DISCOVERY Alpha study).
AB  - BACKGROUND: The majority of clinical trials investigating the clinical benefits
      of lipid-lowering therapies (LLTs) have focused on North American or western and
      nothern European populations. Therefore, it is timely to confirm the efficacy of
      these agents in other patient populations in routine clinical practice.
      OBJECTIVE: The aim of the Direct Statin COmparison of low-density lipoprotein
      cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)
      Alpha study was to compare the effects of rosuvastatin 10 mg with those of
      atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of
      European and Other Societies on Cardiovascular Disease Prevention in Clinical
      Practice guidelines. METHODS: This randomized, open-label, parallel-group study
      was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia,
      Slovenia), Central and South America (Chile, Dominican Republic, El Salvador,
      Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait,
      Saudi Arabia, United Arab Emirates). Male and female patients aged >=18 years
      with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or >=120
      mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year
      coronary heart disease (CHD) risk >20% or a history of CHD or other established
      atherosclerotic disease were eligible for inclusion in the study. Patients were
      randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD
      for 12 weeks. No formal statistical analyses or comparisons were performed on
      lipid changes between switched and LLT-naive patients because of the different
      lipid inclusion criteria for these patients. The primary end point was the
      proportion of patients achieving 1998 European LDL-C goals after 12 weeks of
      treatment. A subanalysis was performed to assess the effects of statins in
      patients who had received previous statin treatment versus those who were LLT
      naive. Tolerability was assessed using laboratory analysis and direct questioning
      of the patients. RESULTS: A total of 1506 patients (52.1% women, 47.9% men; mean
      [SD] age, 58.2 [10.8] years) participated in the study (rosuvastatin, 1002
      patients; atorvastatin, 504 patients; previous LLT, 567 patients). A
      significantly higher proportion of patients achieved 1998 European LDL-C goals
      after 12 weeks with rosuvastatin 10 mg than with atorvastatin 10 mg (72.5% vs
      56.6%; P < 0.001). Similarly, more patients achieved the 2003 European LDL-C
      goals with rosuvastatin 10 mg compared with atorvastatin 10 mg (57.5% vs 39.2%).
      Rosuvastatin 10 mg was associated with a significantly greater change in LDL-C
      levels compared with atorvastatin 10 mg, in patients who were LLT-naive (LDL-C: 
      44.7% vs -33.9%; P < 0.001) and in patients who had received previous LLT (LDL-C:
      -32.0% vs -26.5%; P = 0.006). TG levels were also decreased with rosuvastatin 10
      mg and atorvastatin 10 mg, although there was no significant difference between
      treatments. Similarly, there was no significant difference in the increase in
      high-density lipoprotein cholesterol levels between treatments. The most common
      adverse events overall were headache 16/1497 (1.1%), myalgia 10/1497 (0.7%), and
      nausea 10/1497 (0.7%). CONCLUSIONS: In this study in patients with primary
      hypercholesterolemia in clinical practice, greater reductions in LDL-C levels
      were achieved with a starting dose (10 mg) of rosuvastatin compared with
      atorvastatin 10 mg, with more patients achieving European LDL-C goals. Both
      treatments were well tolerated.

PMID- 24936120
TI  - The Interplay of Stress and Attachment in Individuals Weathering Loss of
      Employment.

PMID- 24936121
TI  - Utility of absolute lymphocyte count as a surrogate marker of CD4 cell counts: Is
      it useful?
AB  - BACKGROUND: Human immunodeficiency virus (HIV) management has witnessed paradigm
      changes over the past decade. In the early era, Absolute lymphocyte counts (ALC)
      were used as an inexpensive, indirect marker of immunity status. With time, CD4
      lymphocyte counts and HIV RNA levels have become a standard of care for follow up
      of people living with HIV/AIDS (PLHA). Wide disparities between resource rich and
      poor countries, rekindles the need for an inexpensive surrogate marker for CD4
      lymphocyte counts. Multiple studies in the past including one by Sen S et al, in
      2011 did not validate ALC as a surrogate marker of CD4 lymphocyte counts and had
      recommended a similar study at another centre to validate the same.(1) Recently
      few publications have suggested that ALC may be used as a proxy marker to CD4
      lymphocyte counts in resource poor areas.(2) With this backdrop we decided to
      evaluate the association if any, of ALC as a surrogate marker to CD4 lymphocyte
      counts. METHODS: ALC and CD4 lymphocyte counts measurements of 241 patients at
      our HIV/AIDS referral centre were assessed over a period of 13 months. RESULTS:
      Pearson correlation coefficient, coefficient of determination and standard
      statistical methods revealed modest linear correlation between ALC and CD4
      lymphocyte counts which was statistically significant but did not have clinical
      significance. CONCLUSION: We recommend that time has come to call curtains down
      on ALC as a surrogate marker for CD4 lymphocyte count.

PMID- 24936122
TI  - "Mesenteric cyst: A rare intra-abdominal tumour".

PMID- 24936123
TI  - An urgent need for introduction of fourth-generation Ag-Ab based EIA for
      detection of HIV infection.

PMID- 24936124
TI  - Validation of Datascope Accutorr PlusTM using British Hypertension Society (BHS)
      and Association for the Advancement of Medical Instrumentation (AAMI) protocol
      guidelines.
AB  - OBJECTIVE: To assure the accuracy and reliability of blood pressure measurement
      by non-invasive blood pressure monitor using Datascope Accutorr PlusTM (Paramus,
      NJ, USA) against mercury manometer, among adult male participants. METHOD: Eighty
      participants from a family physician's office at a teaching hospital were
      recruited. One hundred and sixty measurements of blood pressure were performed
      according to BHS technique protocol. STATISTICAL ANALYSIS: Descriptive analysis
      was done according to the AAMI and BHS protocol guidelines. The limits of
      agreement between the device and the standard were plotted using the method of
      Bland and Altman plot. RESULTS: The mean difference +/- SD between the Datascope
      Acutorr PlusTM and observer was 2.7 +/- 5.2 mm Hg and 1.5 +/- 3.26 mm Hg for
      systolic and diastolic blood pressure, respectively. Datascope Acutorr PlusTM
      obtained A/A grading for both systolic and diastolic blood pressure. CONCLUSION:
      Datascope Accutorr PlusTM (Paramus, NJ, USA) satisfies BHS and AAMI validation
      protocols for both systolic and diastolic BP and may be recommended for everyday
      use for BP monitoring at home and in clinical use for adult population.

PMID- 24936125
TI  - Short term follow-up of prediabetics undergoing elective percutaneous coronary
      intervention.
AB  - BACKGROUND: Epidemiologic evidence suggests that the complications of diabetes
      begin early in the progression from normal glucose tolerance to frank diabetes.
      Prediabetes is defined as people with impaired fasting glucose (IFG) or impaired
      glucose tolerance (IGT), some of whom in fact already have the characteristic
      microvascular changes resulting from diabetes itself. METHODS AND RESULTS: This
      study was conducted on 108 patients presenting to Ain Shams University
      Catheterization Laboratory for elective percutaneous coronary intervention using
      bare metal stents (48 diabetic patients, 30 pre-diabetic patients and 30 non
      diabetic patients). All patients underwent bare metal stent deployment either
      preceded by balloon dilatation or not. Follow-up was done at three and six months
      for major adverse cardiac & cerebral events (cardiovascular death, acute coronary
      syndrome, cerebrovascular stroke, target vessel revascularization). RESULTS: Our
      findings demonstrate that there was no statistically significant difference
      between patients of the three different study groups regarding composite end
      point of death, stroke, acute coronary syndrome and target vessel
      revascularization at three months follow-up (diabetics = 18.8%, pre-diabetics =
      13.3%, non diabetics = 3.3%, p-value = 0.1), but there was a highly statistical
      difference between them regarding acute coronary syndrome (diabetics = 43%, pre
      diabetics = 26%, non diabetics = 10%, p-value = 0.006) at six months follow-up.
      CONCLUSION: Prediabetes, though not a disease entity by itself is associated with
      of risk for both macrovascular and increasingly, microvascular pathology. It is
      important to identify these conditions to prevent incident diabetes and to take
      measures to stop the vascular complications. Our study findings revealed that
      complications of diabetes may begin early as patients are suffering impaired
      glucose homeostasis, which warrants further evaluation in larger studies.

PMID- 24936126
TI  - Is increasing the dose of Entecavir effective in partial virological responders?
AB  - OBJECTIVE: To analyze the effect of increasing Entecavir (ETV) dosage in patients
      with chronic hepatitis B (CHB) who partially responded to ETV after 1 year.
      METHODS: Twenty-three hepatitis B e antigen (HBeAg)-positive and 36 HBeAg
      negative patients with CHB were treated with ETV 0.5 mg daily. After 1 year of
      the treatment, those with detectable hepatitis B virus (HBV-DNA) were randomized
      to either ETV 0.5 mg or 1 mg daily. The resistance to ETV was excluded. Both
      groups received ETV for 3 years. The groups were compared in aspects of
      undetectable DNA. RESULTS: Group 1 was given 0.5 mg ETV and included 32 patients
      (20 HBeAg-negative and 12 HBeAg-positive). Group 2 was given 1 mg ETV and
      consisted of 27 patients (16 HBeAg-negative and eleven HBeAg-positive). Group 2
      had more effective suppression of HBV-DNA while both groups had comparable rates
      of HBeAg loss (58% and 63% for group 1 and group 2, respectively) and alanine
      transaminase (ALT) normalization at the end of 4 years. CONCLUSION: Increasing
      ETV dose from 0.5 mg to 1 mg after 1 year of ETV treatment may provide an
      effective suppression of viral replication.

PMID- 24936127
TI  - Evaluation of ceftiofur-PHBV microparticles in rats.
AB  - Despite the high number of antibiotics used for the treatment of infectious
      disease in animals, the development of slow release formulations presents a
      significant challenge, particularly in using novel biomaterials with low cost. In
      this report, we studied the pharmacokinetics, toxicity, and therapeutic activity
      of ceftiofur-PHBV (ceftiofur-poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) in
      rats. The pharmacokinetic study demonstrated a sustained release of ceftiofur
      into the bloodstream, with detectable levels over the minimum inhibitory
      concentration for at least 17 days after a single intramuscular injection of
      ceftiofur-PHBV (10 mg/kg weight). In addition, the toxicological evaluation of
      biochemical, hematological, and coagulation blood parameters at the therapeutic
      dose demonstrated the safety of ceftiofur-PHBV, with no adverse effects. In
      addition, ceftiofur-PHBV exhibited a therapeutic effect for a longer time period
      than the nonencapsulated ceftiofur in rats challenged with Salmonella
      Typhimurium. The slow release of ceftiofur from the ceftiofur-PHBV, its low
      toxicity in the blood parameters evaluated, and the efficacy in the rats infected
      with Salmonella Typhimurium make ceftiofur-PHBV a strong candidate for
      biotechnological applications in the veterinary industry. 

PMID- 24936128
TI  - Progress of clinical research on targeted therapy combined with thoracic
      radiotherapy for non-small-cell lung cancer.
AB  - The combination of radiotherapy and targeted therapy is an important approach in
      the application of targeted therapy in clinical practice, and represents an
      important opportunity for the development of radiotherapy itself. Numerous
      agents, including epidermal growth factor receptor, monoclonal antibodies,
      tyrosine kinase inhibitors, and antiangiogenic therapies, have been used for
      targeted therapy. A number of studies of radiotherapy combined with targeted
      therapy in non-small-cell lung carcinoma have been completed or are ongoing. This
      paper briefly summarizes the drugs involved and the important related clinical
      research, and indicates that considerable progress has been made with the joint
      efforts of the two disciplines. Many issues, including drug selection,
      identification of populations most likely to benefit, timing of administration of
      medication, and side effects of treatment require further investigation. However,
      further fundamental research and accumulation of clinical data will provide a
      more comprehensive understanding of these therapies. Targeted therapy in
      combination with radiotherapy has a bright future. 

PMID- 24936129
TI  - Synthesis and characterization of different immunogenic viral nanoconstructs from
      rotavirus VP6 inner capsid protein.
AB  - In order to deliver low-cost viral capsomeres from a large amount of soluble
      viral VP6 protein from human rotavirus, we developed and optimized a
      biotechnological platform in Escherichia coli. Specifically, three different
      expression protocols were compared, differing in their genetic constructs, ie, a
      simple native histidine-tagged VP6 sequence, VP6 fused to thioredoxin, and VP6
      obtained with the newly described small ubiquitin-like modifier (SUMO) fusion
      system. Our results demonstrate that the histidine-tagged protein does not escape
      the accumulation in the inclusion bodies, and that SUMO is largely superior to
      the thioredoxin-fusion tag in enhancing the expression and solubility of VP6
      protein. Moreover, the VP6 protein produced according to the SUMO fusion tag
      displays well-known assembly properties, as observed in both transmission
      electron microscopy and atomic force microscopy images, giving rise to either VP6
      trimers, 60 nm spherical virus-like particles, or nanotubes a few microns long.
      This different quaternary organization of VP6 shows a higher level of
      immunogenicity for the elongated structures with respect to the spheres or the
      protein trimers. Therefore, the expression and purification strategy presented
      here - providing a large amount of the viral capsid protein in the native form
      with relatively simple, rapid, and economical procedures - opens a new route
      toward large-scale production of a more efficient antigenic compound to be used
      as a vaccination tool or as an adjuvant, and also represents a top-quality
      biomaterial to be further modified for biotechnological purposes. 

PMID- 24936130
TI  - Amorphous silica nanoparticles impair vascular homeostasis and induce systemic
      inflammation.
AB  - Amorphous silica nanoparticles (SiNPs) are being used in biomedical,
      pharmaceutical, and many other industrial applications entailing human exposure.
      However, their potential vascular and systemic pathophysiologic effects are not
      fully understood. Here, we investigated the acute (24 hours) systemic toxicity of
      intraperitoneally administered 50 nm and 500 nm SiNPs in mice (0.5 mg/kg). Both
      sizes of SiNPs induced a platelet proaggregatory effect in pial venules and
      increased plasma concentration of plasminogen activator inhibitor-1. Elevated
      plasma levels of von Willebrand factor and fibrinogen and a decrease in the
      number of circulating platelets were only seen following the administration of 50
      nm SiNPs. The direct addition of SiNPs to untreated mouse blood significantly
      induced in vitro platelet aggregation in a dose-dependent fashion, and these
      effects were more pronounced with 50 nm SiNPs. Both sizes of SiNPs increased
      lactate dehydrogenase activity and interleukin 1beta concentration. However,
      tumor necrosis factor alpha concentration was only increased after the
      administration of 50 nm SiNPs. Nevertheless, plasma markers of oxidative stress,
      including 8-isoprostane, thiobarbituric acid reactive substances, catalase, and
      glutathione S-transferase, were not affected by SiNPs. The in vitro exposure of
      human umbilical vein endothelial cells to SiNPs showed a reduced cellular
      viability, and more potency was seen with 50 nm SiNPs. Both sizes of SiNPs caused
      a decrease in endothelium-dependent relaxation of isolated small mesenteric
      arteries. We conclude that amorphous SiNPs cause systemic inflammation and
      coagulation events, and alter vascular reactivity. Overall, the effects observed
      with 50 nm SiNPs were more pronounced than those with 500 nm SiNPs. These
      findings provide new insight into the deleterious effect of amorphous SiNPs on
      vascular homeostasis. 

PMID- 24936131
TI  - Importance of antimicrobial stewardship to the English National Health Service.
AB  - Antimicrobials are an extremely valuable resource across the spectrum of modern
      medicine. Their development has been associated with dramatic reductions in
      communicable disease mortality and has facilitated technological advances in
      cancer therapy, transplantation, and surgery. However, this resource is
      threatened by the dwindling supply of new antimicrobials and the global increase
      in antimicrobial resistance. There is an urgent need for antimicrobial
      stewardship (AMS) to protect our remaining antimicrobials for future generations.
      AMS emphasizes sensible, appropriate antimicrobial management for the benefit of
      the individual and society as a whole. Within the English National Health Service
      (NHS), a series of recent policy initiatives have focused on all aspects of AMS,
      including best practice guidelines for antimicrobial prescribing, enhanced
      surveillance mechanisms for monitoring antimicrobial use across primary and
      secondary care, and new prescribing competencies for doctors in training. Here we
      provide a concise summary to clarify the current position and importance of AMS
      within the NHS and review the evidence base for AMS recommendations. The evidence
      supports the impact of AMS strategies on modifying prescribing practice in
      hospitals, with beneficial effects on both antimicrobial resistance and the
      incidence of Clostridium difficile, and no evidence of increased sepsis-related
      mortality. There is also a promising role for novel diagnostic technologies in
      AMS, both in enhancing microbiological diagnosis and improving the specificity of
      sepsis diagnosis. More work is needed to establish an evidence base for
      interventions to improve public and patient education regarding the role of
      antibiotics in common clinical syndromes, such as respiratory tract infection.
      Future priorities include establishing novel approaches to antimicrobial
      management (eg, duration of therapy, combination regimens) to protect against
      resistance and working with the pharmaceutical industry to promote the
      development of new antimicrobials. 

PMID- 24936132
TI  - Physiotherapy intervention as a complementary treatment for people living with
      HIV/AIDS.
AB  - BACKGROUND: The advent of highly active antiretroviral therapy has dramatically
      extended the life expectancy of people living with human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome. Despite this increased longevity, HIV
      disease and its pharmacological treatment can cause long-term and acute health
      complications, many of which can be treated successfully by physiotherapy. The
      purpose of this paper is to report the effect of a 12-week rehabilitation program
      on several health-related markers in a 43-year-old woman living with HIV.
      METHODS: This case study examined the effect of a 12-week exercise and manual
      therapy intervention on morphology, pain, cardiopulmonary fitness, strength,
      neurological balance, immune markers (CD4 cell count), and quality of life in a
      43-year-old woman living with HIV. RESULTS: The results showed complete
      elimination of pain and shortness of breath on exertion. There was also a
      reduction in resting heart rate, waist circumference, exercise duration, muscle
      strength, and endurance. The patient showed an increase in peak expiratory flow
      rate, maximal heart rate attained, upper arm, forearm, and thigh circumference,
      and CD4+ cell count. The patient also showed improvements in the quality of life
      domains of general health, pain, energy/fatigue, social and physical functioning,
      and emotional well-being. CONCLUSION: Physiotherapy interventions consisting of
      exercise and manual therapy appear beneficial in several areas as an adjunct
      therapy in HIV management.

PMID- 24936134
TI  - Review on in vivo and in vitro methods evaluation of antioxidant activity.
AB  - A good number of abstracts and research articles (in total 74) published, so far,
      for evaluating antioxidant activity of various samples of research interest were
      gone through where 407 methods were come across, which were repeated from 29
      different methods. These were classified as in vitro and in vivo methods. And
      those are described and discussed below in this review article. In the later part
      of this review article, frequency of in vitro as well as in vivo methods is
      analyzed with a bar diagram. Solvents are important for extracting antioxidants
      from natural sources. Frequency of solvents used for extraction is also portrayed
      and the results are discussed in this article. As per this review there are 19 in
      vitro methods and 10 in vivo methods that are being used for the evaluation of
      antioxidant activity of the sample of interest. DPPH method was found to be used
      mostly for the in vitro antioxidant activity evaluation purpose while LPO was
      found as mostly used in vivo antioxidant assay. Ethanol was with the highest
      frequency as solvent for extraction purpose. 

PMID- 24936133
TI  - Biopharmaceutical applications of nanogold.
AB  - The application of nanogold in biopharmaceutical field is reviewed in this work.
      The properties of nanogold including nanogold surface Plasmon absorption and
      nanogold surface Plasmon light scattering are illustrated. The physical,
      chemical, biosynthesis methods of nanogold preparation are presented. Catalytic
      properties as well as biomedical applications are highlighted as one of the most
      important applications of nanogold. Biosensing, and diagnostic and therapeutic
      applications of gold nanoparticles are evaluated. Moreover, gold nanoparticles in
      drugs, biomolecules and proteins' delivery are analyzed. Gold nanoparticles for
      the site-directed photothermal applications are reviewed as the most fruitful
      research area in the future. 

PMID- 24936135
TI  - Microalgae and wastewater treatment.
AB  - Organic and inorganic substances which were released into the environment as a
      result of domestic, agricultural and industrial water activities lead to organic
      and inorganic pollution. The normal primary and secondary treatment processes of
      these wastewaters have been introduced in a growing number of places, in order to
      eliminate the easily settled materials and to oxidize the organic material
      present in wastewater. The final result is a clear, apparently clean effluent
      which is discharged into natural water bodies. This secondary effluent is,
      however, loaded with inorganic nitrogen and phosphorus and causes eutrophication
      and more long-term problems because of refractory organics and heavy metals that
      are discharged. Microalgae culture offers an interesting step for wastewater
      treatments, because they provide a tertiary biotreatment coupled with the
      production of potentially valuable biomass, which can be used for several
      purposes. Microalgae cultures offer an elegant solution to tertiary and quandary
      treatments due to the ability of microalgae to use inorganic nitrogen and
      phosphorus for their growth. And also, for their capacity to remove heavy metals,
      as well as some toxic organic compounds, therefore, it does not lead to secondary
      pollution. In the current review we will highlight on the role of micro-algae in
      the treatment of wastewater. 

PMID- 24936136
TI  - Effect of salt on survival and P-solubilization potential of phosphate
      solubilizing microorganisms from salt affected soils.
AB  - A total of 23 phosphate solubilizing bacteria (PSB) and 35 phosphate solubilizing
      fungi (PSF) were isolated from 19 samples of salt affected soils. The ability of
      12 selected PSB and PSF to grow and solubilize tricalcium phosphate in the
      presence of different concentrations of NaCl was examined. Among 12 PSB,
      Aerococcus sp. strain PSBCRG1-1 recorded the highest (12.15) log viable cell
      count at 0.4 M NaCl concentration after 7 days after incubation (DAI) and the
      lowest log cell count (1.39) was recorded by Pseudomonas aeruginosa strain PSBI3
      1 at 2.0 M NaCl concentration after 24 h of incubation. Highest mycelial dry
      weight irrespective of NaCl concentrations was recorded by the Aspergillus
      terreus strain PSFCRG2-1 (0.567 g). The percent P i release, in general, was
      found to increase with increase in NaCl concentration up to 0.8 M for bacterial
      solubilization and declined thereafter. At 15 DAI, strain Aerococcus sp. strain
      PSBCRG1-1 irrespective of NaCl concentrations showed the maximum P-solubilization
      (12.12%) which was significantly superior over all other isolates. The amount of
      P i released in general among PSF was found to decrease with increase in NaCl
      concentration at all the incubation periods. Aspergillus sp. strain PSFNRH-2
      (20.81%) recorded the maximum P i release irrespective of the NaCl concentrations
      and was significantly superior over all other PSF at 7 DAI. 

PMID- 24936137
TI  - Association between plasma adiponectin levels and decline in forced expiratory
      volume in 1 s in a general Japanese population: the Takahata study.
AB  - BACKGROUND: Adiponectin is an anti-inflammatory and cardio-protective cytokine.
      However, several studies have demonstrated that plasma adiponectin levels were
      inversely associated with pulmonary function in patients with chronic obstructive
      pulmonary disease, suggesting a proinflammatory or pulmonary-destructive role. It
      is still unclear whether adiponectin is a potent biomarker predicting declines in
      pulmonary function. The aim of this study was to investigate the association
      between adiponectin and pulmonary function among Japanese individuals who
      participated in an annual health check-up. METHODS: Spirometry and blood
      sampling, including measurements of plasma adiponectin, were performed for 3,253
      subjects aged 40 years or older who participated in a community-based annual
      health check-up in Takahata, Japan from 2004 to 2006. In 2011, spirometry was re
      performed, and the data from 872 subjects (405 men and 467 women) were available
      for a longitudinal analysis. RESULTS: Plasma adiponectin levels were found to be
      significantly associated with age, body mass index (BMI), and alanine
      aminotransferase (ALT), triglycerides (TG), and high-density lipoprotein
      cholesterol (HDL-c) levels among both men and women in the study population.
      Plasma adiponectin levels were found to be associated with lifetime cigarette
      consumption (Brinkman index, BI) in men only. Plasma adiponectin levels were
      inversely correlated with forced expiratory volume in 1 s (FEV1) per forced vital
      capacity in both men and women. In addition, the annual change in FEV1 was
      inversely associated with plasma adiponectin levels in both genders. A multiple
      linear regression analysis revealed that this association was independent of
      other confounding factors such as age, BMI, BI, ALT, TG, and HDL-c. CONCLUSIONS:
      The results of the present study suggest that adiponectin levels are predictive
      of declines in FEV1 in the general population.

PMID- 24936138
TI  - MicroRNA-365 inhibits vascular smooth muscle cell proliferation through targeting
      cyclin D1.
AB  - MicroRNA-365 (miR-365) plays crucial roles in regulating cell proliferation,
      apoptosis and differentiation in various cell types. However, its function in
      vascular smooth muscle cells (VSMCs) is largely unknown. In our study, we found
      miR-365 was highly expressed in adult rat carotid arteries, but was significantly
      decreased in rat carotid arteries after balloon injury, a process involving
      neointima formation and VSMC proliferation. In vitro, the miR-365 significantly
      inhibited cell proliferation of isolated primary rat aortic VSMCs. Furthermore,
      we identified that cyclin D1 was a direct target of miR-365 in VSMCs. The miR-365
      suppressed cyclin D1 expression on both mRNA and protein level. Luciferase
      reporter assay demonstrated that miR-365 inhibited cyclin D1 through targeting
      its 3'UTR. Importantly, cyclin D1 overexpression rescued the inhibitory effect of
      miR-365 on VSMCs proliferation. Taken together, by our studies, we identified a
      new MicroRNA, miR-365, involving in the pathological process of vascular injury,
      which inhibits VSMC proliferation through targeting cyclinD1. 

PMID- 24936139
TI  - Impaired cognitive executive dysfunction in adult treated hypertensives with a
      confirmed diagnosis of poorly controlled blood pressure.
AB  - BACKGROUND: High blood pressure (BP) poses a major risk for cognitive decline.
      Aim of the study was to highlight the relationship between cognitive assessment
      scores and an effective therapeutic BP control. METHODS: By medical visit and
      ambulatory BP monitoring (ABPM), we studied 302 treated hypertensives, subdivided
      according to office/daytime BP values into 120 with good (GC) and 98 poor (PC) BP
      control, 40 with "white coat hypertension" (WCH) and 44 a "masked-hypertension"
      phenomenon (MH). Patients underwent neuropsychological assessment to evaluate
      global cognitive scores at the Mini Mental State Examination (MMSE) and Frontal
      Assessment Battery (FAB) and attention/executive functions (Delayed Recall, Digit
      Span Forwards, Digit Span Backwards, Selective Attention, Verbal Fluency, Stroop
      Test and Clock Drawing). Carotid intima-media thickness (IMT) served as the index
      of vascular damage. RESULTS: There were no differences among the groups in terms
      of gender, age, education, metabolic assessment, clinical history and
      hypertension treatment. GC presented lower office and ambulatory BP values and
      IMT. PC performed worse than GC on global executive and attention functions,
      especially executive functions. In PC, office systolic BP (SBP) was significantly
      associated to the MMSE and FAB scores and, in particular, to Verbal Fluency,
      Stroop Errors and Clock Drawing tests. Office diastolic BP (DBP) was associated
      to Selective attention, nocturnal SBP to Digit Span backwards and Verbal Fluency.
      Worse cognitive assessment scores were obtained in WCH than GC. CONCLUSIONS: The
      findings showed that in adult treated hypertensives, a poor BP control, as both
      doctor's office and daytime scores, is associated to impaired global cognitive
      and especially executive/attention functions.

PMID- 24936140
TI  - Prognostic CpG methylation biomarkers identified by methylation array in
      esophageal squamous cell carcinoma patients.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer
      with poor prognosis. We aimed to identify a panel of CpG methylation biomarkers
      for prognosis prediction of ESCC patients. METHODS: Illumina's GoldenGate
      methylation array, supervised principal components, Kaplan-Meier survival
      analyses and Cox regression model were conducted on dissected tumor tissues from
      a training cohort of 40 ESCC patients to identify potential CpG methylation
      biomarkers. Pyrosequencing quantitative methylation assay were performed to
      validate prognostic CpG methylation biomarkers in 61 ESCC patients. The
      correlation between DNA methylation and RNA expression of a validated marker,
      SOX17, was examined in a validation cohort of 61 ESCC patients. RESULTS: We
      identified a panel of nine CpG methylation probes located at promoter or exon1
      region of eight genes including DDIT3, FES, FLT3, NTRK3, SEPT5, SEPT9, SOX1, and
      SOX17, for prognosis prediction in ESCC patients. Risk score calculated using the
      eight-gene panel statistically predicted poor outcome for patients with high risk
      score. These eight-gene also showed a significantly higher methylation level in
      tumor tissues than their corresponding normal samples in all patients analyzed.
      In addition, we also detected an inverse correlation between CpG hypermethylation
      and the mRNA expression level of SOX17 gene in ESCC patients, indicating that DNA
      hypermethylation was responsible for decreased expression of SOX17. CONCLUSIONS:
      This study established a proof-of-concept CpG methylation biomarker panel for
      ESCC prognosis that can be further validated by multiple cohort studies.
      Functional characterization of the eight prognostic methylation genes in our
      biomarker panel could help to dissect the mechanism of ESCC tumorigenesis.

PMID- 24936141
TI  - Spatiotemporal expression of HDAC2 during the postnatal development of the rat
      hippocampus.
AB  - BACKGROUND: Histone acetylation, which is a chromatin modification of histone
      tails, can dynamically regulate the expression of various genes in normal
      development. HDAC2 is a negative regulatory factor of acetylation and closely
      related to learning and memory. NSE is a nerve marker and vital for maintaining
      physiological functions in nervous system. Currently, few studies associated with
      the expression pattern of HDAC2 in postnatal rat hippocampus have been reported.
      This study aimed to explore the temporal and spatial expression pattern of HDAC2,
      helping to reveal the expression characteristics of HDAC2 during postnatal
      neuronal maturation. MATERIALS AND METHODS: With NSE as a biomarker of neuronal
      maturation at postnatal days 1, 3, 7 and weeks 2, 4, and 8 (P1D, P3D, P7D, P2W,
      P4W, P8W), the expression patterns of HDAC2 in rat hippocampus were examined
      using real-time PCR and western blotting. Additionally, the subcellular
      distribution of HDAC2 was analysed by immunofluorescence. RESULTS: We found that
      HDAC2 was highly expressed in the neonatal period and decreased gradually. HDAC2
      expression was widely distributed in neurons of hippocampal CA1, CA3 and DG
      regions and gradually shifted from the nucleus to the cytoplasm during postnatal
      development. Altogether, the expression of HDAC2 decreased gradually with
      different subcellular localizations throughout development. CONCLUSIONS: The
      observed results indicate that the expression levels of HDAC2 become lower and
      with different subcellular localizations in neurons during hippocampal neuronal
      maturation, suggesting the specific expression characteristics of HDAC2 might
      play an important role during postnatal learning-memory function and development.

PMID- 24936142
TI  - Automated sleep apnea quantification based on respiratory movement.
AB  - Obstructive sleep apnea (OSA) is a prevalent and treatable disorder of
      neurological and medical importance that is traditionally diagnosed through multi
      channel laboratory polysomnography(PSG). However, OSA testing is increasingly
      performed with portable home devices using limited physiological channels. We
      tested the hypothesis that single channel respiratory effort alone could support
      automated quantification of apnea and hypopnea events. We developed a respiratory
      event detection algorithm applied to thoracic strain-belt data from patients with
      variable degrees of sleep apnea. We optimized parameters on a training set (n=57)
      and then tested performance on a validation set (n=59). The optimized algorithm
      correlated significantly with manual scoring in the validation set (R2=0.73 for
      training set, R2=0.55 for validation set; p<0.05). For dichotomous
      classification, the AUC was >0.92 and >0.85 using apnea-hypopnea index cutoff
      values of 5 and 15, respectively. Our findings demonstrate that manually scored
      AHI values can be approximated from thoracic movements alone. This finding has
      potential applications for automating laboratory PSG analysis as well as
      improving the performance of limited channel home monitors.

PMID- 24936143
TI  - Integration of the hybrid adenoretroviral vector AdLTR-luc involves both MoMLV
      elements flanking the transgene.
AB  - Vector delivery is still a bottleneck for gene therapy. To overcome some
      disadvantages of adenoviral and retroviral vectors, we developed a hybrid vector.
      This hybrid vector, AdLTR-luc, was created by adding two elements from Moloney
      murine leukemia virus (MoMLV) flanking the luciferase cDNA into an E1/E3-deleted,
      replication deficient serotype 5 adenovirus vector (Zheng et al., Nature
      Biotechnol, 2000), and demonstrated that the MoMLV element upstream of the
      luciferase cDNA was broken during the integration event. The purpose of the
      current study was to determine if the MoMLV element downstream of the luciferase
      cDNA was also broken when integration occurred. We used the same A5 cell clones
      (#10 and 11) from the earlier the paper along with restriction endonuclease
      digestions, plus Southern hybridization, and PCR. Southern hybridization
      indicated that the luciferase cDNA was intact in the cloned cells. Results from
      Xho I and Sal I digestions showed that integration occurred in cloned cells.
      Southern hybridizations after Nco I digestion suggested that there was a break in
      both MoMLV elements, upstream and downstream of the luciferase cDNA. After DNA
      digestion with Not I, hybridization analyses indicated that the MoMLV upstream
      element was broken during integration. Digestion of genomic DNA with either Xba
      I/Kpn I, Bam HI/Sac I, or Bam HI/Nco I demonstrated that the MoMLV downstream
      element was also broken during integration. A PCR assay was unable to amplify the
      junctional region between the downstream MoMLV element and the adenoviral E2B
      gene, consistent with a break in that element. Although AdLTR-luc integration is
      atypical (Zheng et al., Nature Biotechnol, 2000), the present results suggest
      that both MoMLV elements have important roles in this event. 

PMID- 24936144
TI  - Expression, regulation and function of microRNAs in multiple sclerosis.
AB  - MicroRNAs (miRNAs) are single-stranded 19-25 nucleotide-long RNAs and have an
      important role in post-transcriptional gene silencing. It has been demonstrated
      that miRNAs are dysregulated in patients with multiple sclerosis (MS). For
      instance, miR-21, miR-142-3p, miR-146a, miR-146b, miR-155 and miR-326 were up
      regulated in both peripheral blood mononuclear cells (PBMCs) and brain white
      matter lesions from MS patients and mouse model as well. These up-regulated
      miRNAs may be used as a signature for MS and play critical roles in MS
      pathogenesis. Moreover, miR-15a, miR-19a, miR-22, miR-210 and miR-223 were up
      regulated in both regulatory T cells (Tregs) and other samples such as plasma,
      blood cells, PBMCs and brain white matter tissues from MS patients, suggesting
      that these up-regulated miRNAs and Tregs may also play a role in MS pathogenesis.
      Contrarily, other miRNAs such as miR-15a, miR-15b, miR-181c and miR-328 were down
      regulated in MS. Drugs such as interferon-beta and glatiramer acetate for MS
      treatment may regulate miRNA expression and thus have benefits for MS patients.
      The dysregulated miRNAs such as miR-155 and miR-326 may be used as diagnostic
      markers and therapeutic targets for MS. 

PMID- 24936145
TI  - Screening tests using serum tissue transglutaminase IgA may facilitate the
      identification of undiagnosed celiac disease among Japanese population.
AB  - The prevalence of celiac disease (CD) among Japanese population has been unknown,
      whereas it has been increasingly recognized in the US and in the European
      countries. The aim of the present study is to identify possible cases with CD
      among Japanese population and clarify the relevance of screening for the disease.
      We conducted a serologic screening for the disease among 710 Japanese patients
      and 239 healthy volunteers at a local tertiary teaching hospital, using an anti
      tissue transglutaminase IgA (TTG-IgA) test, and histological examination of the
      small intestines from the TTG-IgA positive subjects. There were no TTG-IgA
      positive sera among the healthy volunteers. Twenty of the patients (2.8%),
      including eight with malignant lymphoma, were tested positive for TTG-IgA. The
      histological examination of the eleven patients among those with positive TTG
      IgA, seven showed villous atrophy and partial lymphocytes infiltration in the
      mucosa, which could be compatible to mucosal changes observed in CD. Five of them
      had non-Hodgkin lymphoma in the gastrointestinal tracts. Serologic tests using
      TTG-IgA might be relevant to screen for those with undiagnosed CD among Japanese
      population. 

PMID- 24936146
TI  - Frequent co-expression of miRNA-5p and -3p species and cross-targeting in induced
      pluripotent stem cells.
AB  - BACKGROUND: A miRNA precursor generally gives rise to one major miRNA species
      derived from the 5' arm, and are called miRNA-5p. However, more recent studies
      have shown co-expression of miRNA-5p and -3p, albeit in different concentrations,
      in cancer cells targeting different sets of transcripts. Co-expression and
      regulation of the -5p and -3p miRNA species in stem cells, particularly in the
      reprogramming process, have not been studied. METHODS: In this work, we
      investigated co-expression and regulation of miRNA-5p and -3p species in human
      induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and
      embryonic stem cells (ESC) using a nanoliter-scale real-time PCR microarray
      platform that included 1,036 miRNAs. RESULTS: In comparing iPSC and ESC, only 32
      miRNAs were found to be differentially expressed, in agreement of the ESC-like
      nature of iPSC. In the analysis of reprogramming process in iPSCs, 261 miRNAs
      were found to be differentially expressed compared with the parental MSC and pre
      adipose tissue, indicating significant miRNA alternations in the reprogramming
      process. In iPSC reprogrammed from MSC, there were 88 miRNAs (33.7%), or 44 co
      expressed 5p/3p pairs, clearly indicating frequent co-expression of both miRNA
      species on reprogramming. Of these, 40 pairs were either co-up- or co
      downregulated indicating concerted 5p/3p regulation. The 5p/3p species of only 4
      pairs were regulated in reverse directions. Furthermore, some 5p/3p species of
      the same miRNAs were found to target the same transcript and the same miRNA may
      cross-target different transcripts of proteins of the G1/S transition of the cell
      cycle; 5p/3p co-targeting was confirmed in stem-loop RT-PCR. CONCLUSION: The
      observed cross- and co-regulation by paired miRNA species suggests a fail-proof
      scheme of miRNA regulation in iPSC, which may be important to iPSC pluripotency.

PMID- 24936147
TI  - Determinants of right ventricular muscle mass in idiopathic dilated
      cardiomyopathy: impact of left ventricular muscle mass and pulmonary
      hypertension.
AB  - INTRODUCTION: Although chronic pulmonary hypertension and right ventricular (RV)
      function carry important functional and prognostic implications in idiopathic
      dilated cardiomyopathy (IDC), little information on RV muscle mass (RVMM) and its
      determinants has been published. METHODS: Our study comprised thirty-five
      consecutive patients with IDC, left ventricular (LV) ejection fraction<40% and
      NYHA class>=2. Hemodynamic data and parameters on LV and RV geometry were derived
      from right heart catheterisation and cardiac magnetic resonance imaging. RESULTS:
      RVMM was normalized to body size using a common linear, body surface area based
      approach (RVMMI) and by an allometric index (RVMM-AI) incorporating adjustment
      for age, height and weight. Stepwise multiple regression analysis revealed that
      pulmonary artery pressure and left ventricular muscle mass were independent
      predictors of RVMM-AI. The interventricular mass ratio of RV and LV mass (IVRM)
      was closely related to RVMM (r=0.79, p<0.001) and total muscle mass (r=0.39,
      p<0.02). However, there was no significant relationship between LVMM and IVMR
      (r=0.17, p=0.32). CONCLUSION: Our data suggest that an increase in RV mass in IDC
      may be explained by two mechanisms: First, as a consequence of the myopathic
      process itself resulting in a balanced hypertrophy of both ventricles. Second,
      due to the chamber specific burden of pulmonary artery pressure rise, resulting
      in unbalanced RV hypertrophy.

PMID- 24936149
TI  - Meanings of existential uncertainty and certainty for people diagnosed with
      cancer and receiving palliative treatment: a life-world phenomenological study.
AB  - BACKGROUND: Many people around the world are getting cancer and living longer
      with the disease. Thanks to improved treatment options in healthcare, patients
      diagnosed with advanced gastrointestinal cancer can increasingly live for longer.
      Living with cancer creates existential uncertainty, but what does this situation
      mean for the individual? The purpose of the study is to interpret meanings of
      existential uncertainty and certainty for people diagnosed with advanced
      gastrointestinal cancer and receiving palliative treatment. METHODS: This study
      is part of a larger project in which 7 men and 7 women aged between 49 and 79
      participated in a study of information and communication for people with advanced
      gastrointestinal cancer. A total of 66 interviews were conducted with
      participants who were followed up over time. The narrative interviews were
      transcribed verbatim and the texts were analysed in three steps: naive reading,
      structural analysis and interpreted whole by utilizing a phenomenological life
      world approach. RESULTS: THIS STUDY HAS IDENTIFIED DIFFERENT SPHERES IN WHICH
      PEOPLE DIAGNOSED WITH ADVANCED GASTROINTESTINAL CANCER VACILLATE BETWEEN
      EXISTENTIAL UNCERTAINTY AND CERTAINTY: bodily changes, everyday situations,
      companionship with others, healthcare situations and the natural environment.
      Existing in the move between existential uncertainty and certainty appears to
      change people's lives in a decisive manner. The interview transcripts reveal
      aspects that both create existential certainty and counteract uncertainty. They
      also reveal that participants appear to start reflecting on how the new and
      uncertain aspects of their lives will manifest themselves -a new experience that
      lays the foundation for development of knowledge, personal learning and growth.
      CONCLUSIONS: People diagnosed with advanced gastrointestinal cancer and receiving
      palliative care expressed thoughts about personal learning initiated by the
      struggle of living with an uncertain future despite their efforts to live in the
      present. Their personal learning was experienced through a changed life for
      themselves and having to confront their own pending death and develop self
      insight regarding finality of life. Healthcare professionals can try to support
      people receiving palliative treatment for cancer by diversifying avenues for
      their personal growth, thus helping them manage their existential uncertainty and
      gravitate towards greater existential certainty.

PMID- 24936148
TI  - Activation of the PI3K/Akt/mTOR/p70S6K pathway is involved in S100A4-induced
      viability and migration in colorectal cancer cells.
AB  - The S100 protein family member S100A4 regulates various cellular functions.
      Previous studies have shown that elevated expression of S100A4 is associated with
      progression and metastasis of colorectal cancer (CRC). However, little is known
      about whether and how S100A4 contributes to CRC development. In our present
      study, the elevated expression of S100A4 in CRC tissues compared to matched
      adjacent normal tissues was confirmed by immunohistochemistry, semi-quantitative
      RT-PCR and Western blot. Adenovirus-mediated S100A4 overexpression obviously
      enhanced viability and migration of CRC cells, which was detected by MTT assay
      and transwell assay, respectively. Additionally, S100A4 overexpression increased
      the phosphorylation levels of Akt, mTOR and p70S6K. These effects of S100A4 were
      abolished by treatment with either the specific PI3K/Akt inhibitor LY294002, or
      the specific mTOR/p70S6K inhibitor rapamycin. Furthermore, overexpression of
      S100A4 resulted in upregulation of VEGF and downregulation of E-cadherin, which
      were strongly reversed by either LY294002 or rapamycin. Altogether, our results
      demonstrate that activation of the PI3K/Akt/mTOR/p70S6K signaling pathway is
      involved in S100A4-induced viability, migration, upregulation of VEGF and
      downregulation of E-cadherin in CRC cells. 

PMID- 24936150
TI  - Thymidine phosphorylase expression is associated with time to progression in
      patients with metastatic colorectal cancer.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is the cornerstone of chemotherapeutic
      treatment for patients with colorectal cancer. The enzyme thymidine phosphorylase
      (TP) catalyzes the conversion of 5-FU to its active metabolite, 5-fluoro-2'
      deoxyuridine. TP is expressed in tumour epithelial cells and stromal cells,
      particularly in tumour-associated macrophages. These macrophages may affect
      sensitivity to chemotherapy. Previously, we identified TP as a predictive factor
      in microdissected tumour samples of patients with advanced colorectal cancer. In
      the present study, we analysed TP expression in tissues and associated stromal
      cells from patients with advanced colorectal cancer and associated TP levels to
      tumour response and time-to-event variables during first-line chemotherapy
      treatment. We also investigated the association between serum TP levels at the
      time of surgery and gene expression in primary tumour tissues. METHODS: This
      study included 125 patients with metastatic colorectal cancer treated with first
      line 5-FU-based chemotherapy. To quantify TP gene expression levels in tumour
      tissues, real-time polymerase chain reaction was performed using the 7500 Fast
      Real-Time PCR system (Applied Biosystems, Foster City, CA, USA). TP protein
      concentration in matched serum samples was determined using an enzyme-linked
      immunosorbent assay system (USCN Life Science Inc.). RESULTS: The tumour response
      rate was 31%, and 30% of patients exhibited stable disease. No associations
      between TP expression level and age or gender were observed. Levels of TP mRNA in
      mucosa and tumours were positively correlated (r = 0.41, p < 0.01). No
      correlation between TP expression and tumour response rate was observed. Time to
      progression was significantly longer in patients with high TP expression (p <
      0.01). Serum TP protein levels were not associated with tumour response or time
      to-event variables and did not correlate with gene expression in tumour tissues.
      CONCLUSIONS: High TP gene expression in non-microdissected tumour tissues of
      patients with advanced colorectal cancer correlates with longer time to
      progression, which could be related to treatment. These results are in contrast
      to previous studies where microdissected tumour cells were analysed and may be
      due to the presence of adjacent stromal cells. Serum TP protein expression does
      not correlate to TP gene expression in tissues of patients with advanced
      colorectal cancer.

PMID- 24936151
TI  - Reduced expression of PinX1 correlates to progressive features in patients with
      prostate cancer.
AB  - BACKGROUND: Pin2/TRF1 binding protein X1 (PinX1) has been identified as an
      endogenous telomerase inhibitor and a major haploinsufficient tumor suppressor
      gene. Increasing evidence suggests that reduced expression of PinX1 plays a key
      role in tumorigenesis. However, the PinX1 expression status and its correlation
      with the clinicopathological features in prostate cancer (PCa) have not been
      investigated. METHODS: PinX1 mRNA and protein expression in PCa and adjacent
      normal prostate tissues were evaluated by real-time quantitative RT-PCR (qRT-PCR)
      and western blotting. The clinicopathological significance of PinX1 was
      investigated by immunohistochemistry (IHC) analysis on a PCa tissue microarray
      (TMA). The cut-off score for positive expression of PinX1 was determined by the
      receiver operating characteristic (ROC) analysis. The correlation between PinX1
      expression and clinicopathological features of PCa was analyzed by Chi-square
      test. RESULTS: Reduced expression of PinX1 mRNA and protein was observed in the
      majority of PCa, compared with their paired adjacent normal prostate tissues.
      When PinX1 positive expression percentage was determined to be above 60% (area
      under ROC curve = 0.833, P = 0.000), positive expression of PinX1 was observed in
      100% (8/8) of normal prostate tissues and 32.5% (13/40) of PCa tissues by IHC.
      Reduced expression of PinX1 in patients was correlated with advanced clinical
      stage (chi(2) = 10.230, p = 0.017), high Gleason score (chi(2) = 4.019, p =
      0.045), positive regional lymph node metastasis (chi(2) = 10.852, p = 0.004) and
      distant metastasis (chi(2) = 7.965, p = 0.005). CONCLUSIONS: Our findings suggest
      that reduced expression of PinX1 is correlates to progressive features in
      patients with PCa and may serve as a potential marker for diagnosis.

PMID- 24936152
TI  - Hsa-miR-574-5p negatively regulates MACC-1 expression to suppress colorectal
      cancer liver metastasis.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship of MACC-1
      (metastasis-associated in colon cancer 1) and microRNA (miRNA) hsa-miR-574-5p and
      the function of hsa-miR-574-5p in colorectal cancer liver metastasis. METHODS:
      Liver-metastatic nude mice model was constructed by injecting two human
      colorectal cancer cell lines (SW1116 and HCT116) labeled with green fluorescent
      protein (GFP) through spleen, and liver metastasis incidences were evaluated. We
      identified miRNAs that might regulate MACC-1 expression by bioinformatics
      analysis and further investigated the relationship of MACC-1 and hsa-miR-574-5p
      by luciferase reporter assay, quantitative RT-PCR and western blot. The effect of
      hsa-miR-574-5p on colony formation, cell invasion and cell spheroid formation was
      investigated by antisense transfected HCT116 cells and miRNA mimic transfected
      SW1116 cells. RESULTS: The volume of liver metastasis induced by SW1116 cells
      (25.0 +/- 4.4%) was significantly higher than that induced by HCT116 cells.
      Bioinformatics analysis showed hsa-miR-574-5p negatively regulated MACC-1 and
      then their interaction was demonstrated at mRNA and protein level. The direct
      relation between them was confirmed by luciferase reporter assay. And the
      knockdown of has-miR-574-5p demonstrated increased colony formation, cell
      invasion and cell spheroid formation in HCT116 cells, compared to control group
      (P < 0.05). Reverse results were obtained in mimic transfected SW1116 cells.
      CONCLUSION: Our work firstly demonstrated that hsa-miR-574-5p negatively
      regulated MACC-1 expression in colorectal cancer cells. It was partly elucidated
      that hsa-miR-574-5p played a suppressive role in colorectal cancer liver
      metastasis by negatively directing MACC-1 expression, offering a novel
      therapeutic approach for colorectal cancer liver metastasis.

PMID- 24936154
TI  - Headache and Health-Related Job Loss among Disadvantaged Women.

PMID- 24936153
TI  - Early effects of Staphylococcus aureus biofilm secreted products on inflammatory
      responses of human epithelial keratinocytes.
AB  - BACKGROUND: Chronic wounds such as diabetic foot ulcers, pressure ulcers, and
      venous leg ulcers contribute to a considerable amount of mortality in the U.S.
      annually. The inability of these wounds to heal has now been associated with the
      presence of microbial biofilms. The aim of this study was to determine if
      products secreted by S. aureus biofilms play an active role in chronic wounds by
      promoting inflammation, which is a hallmark of chronic wounds. METHODS: In vitro
      experiments were conducted to examine changes in gene expression profiles and
      inflammatory response of human epithelial keratinocytes (HEKa) exposed to
      products secreted by S. aureus grown in biofilms or products secreted by S.
      aureus grown planktonically. RESULTS: After only two hours of exposure, gene
      expression microarray data showed marked differences in inflammatory, apoptotic,
      and nitric oxide responses between HEKa cells exposed to S. aureus biofilm
      conditioned media (BCM) and HEKa cells exposed to S. aureus planktonic
      conditioned media (PCM). As early as 4 hours post exposure, ELISA results showed
      significant increases in IL-6, IL-8, TNFalpha, and CXCL2 production by HEKa cells
      exposed to BCM compared to HEKa cells exposed to PCM or controls. Nitric oxide
      assay data also showed significant increases in nitric oxide production by HEKa
      cells treated with BCM compared to HEKa cells treated with PCM, or controls.
      CONCLUSIONS: Taken together, these results support and extend previous findings
      that indicate products secreted by S. aureus biofilms directly contribute to the
      chronic inflammation associated with chronic wounds.

PMID- 24936155
TI  - Moisture barrier properties of thin organic-inorganic multilayers prepared by
      plasma-enhanced ALD and CVD in one reactor.
AB  - A widely used application of the atomic layer deposition (ALD) and chemical
      vapour deposition (CVD) methods is the preparation of permeation barrier layers
      against water vapour. Especially in the field of organic electronics, these films
      are highly demanded as such devices are very sensitive to moisture and oxygen. In
      this work, multilayers of aluminium oxide (AlO x ) and plasma polymer (PP) were
      coated on polyethylene naphthalate substrates by plasma-enhanced ALD and plasma
      enhanced CVD at 80a"f in the same reactor, respectively. As precursor,
      trimethylaluminium was used together with oxygen radicals in order to prepare AlO
      x , and benzene served as precursor to deposit the PP. This hybrid structure
      allows the decoupling of defects between the single AlO x layers and extends the
      permeation path for water molecules towards the entire barrier film. Furthermore,
      the combination of two plasma techniques in a single reactor system enables short
      process times without vacuum breaks. Single aluminium oxide films by plasma
      enhanced ALD were compared to thermally grown layers and showed a significantly
      better barrier performance. The water vapour transmission rate (WVTR) was
      determined by means of electrical calcium tests. For a multilayer with 3.5 dyads
      of 25-nm AlO x and 125-nm PP, a WVTR of 1.2 * 10 (-3) gm (-2) d (-1) at 60a"f and
      90% relative humidity could be observed. 

PMID- 24936157
TI  - Hexagonal core-shell and alloy Au/Ag nanodisks on ZnO nanorods and their optical
      enhancement effect.
AB  - Au and Ag hybrid hexagonal nanodisks were synthesized on ZnO nanorods' (0002)
      surface via a new two-step deposition-annealing method. The structural,
      compositional, as well as optical investigations were carried out systematically
      to find out the nanodisks' formation mechanism and optical enhancement effect. It
      was shown that the core-shell Au/Ag nanodisk can be formed under rapid annealing
      temperature of 500 degrees C, while Au/Ag alloy nanodisks are formed if higher
      temperatures (>550 degrees C) are applied. The optical effect from these
      nanodisks was studied through photoluminescence and absorption spectroscopy. It
      was found that the carrier-plasmon coupling together and carrier transfer between
      metal and ZnO contribute to the emission enhancement. Furthermore, the results
      suggest that the composition of nanodisk on the vicinity of metal/ZnO interface
      plays an important role in terms of the enhancement factors. 

PMID- 24936156
TI  - Labeling the oily core of nanocapsules and lipid-core nanocapsules with a
      triglyceride conjugated to a fluorescent dye as a strategy to particle tracking
      in biological studies.
AB  - The synthesis of novel fluorescent materials represents a very important step to
      obtain labeled nanoformulations in order to evaluate their biological behavior.
      The strategy of conjugating a fluorescent dye with triacylglycerol allows that
      either particles differing regarding supramolecular structure, i.e.,
      nanoemulsions, nanocapsules, lipid-core nanocapsules, or surface charge, i.e.,
      cationic nanocapsules and anionic nanocapsules, can be tracked using the same
      labeled material. In this way, a rhodamine B-conjugated triglyceride was obtained
      to prepare fluorescent polymeric nanocapsules. Different formulations were
      obtained, nanocapsules (NC) or lipid-core nanocapsules (LNC), using the labeled
      oil and Eudragit RS100, Eudragit S100, or poly(caprolactone) (PCL), respectively.
      The rhodamine B was coupled with the ricinolein by activating the carboxylic
      function using a carbodiimide derivative. Thin layer chromatography, proton
      nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectroscopy
      (FTIR), UV-vis, and fluorescence spectroscopy were used to identify the new
      product. Fluorescent nanocapsule aqueous suspensions were prepared by the solvent
      displacement method. Their pH values were 4.6 (NC-RS100), 3.5 (NC-S100), and 5.0
      (LNC-PCL). The volume-weighted mean diameter (D 4.3) and polydispersity values
      were 150 nm and 1.05 (NC-RS100), 350 nm and 2.28 (NC-S100), and 270 nm and 1.67
      (LNC-PCL). The mean diameters determined by photon correlation spectroscopy (PCS)
      (z-average) were around 200 nm. The zeta potential values were +5.85 mV (NC
      RS100), -21.12 mV (NC-S100), and -19.25 mV (LNC-PCL). The wavelengths of maximum
      fluorescence emission were 567 nm (NC-RS100 and LNC-PCL) and 574 nm (NC-S100).
      Fluorescence microscopy was used to evaluate the cell uptake (human macrophage
      cell line) of the fluorescent nanocapsules in order to show the applicability of
      the approach. When the cells were treated with the fluorescent nanocapsules, red
      emission was detected around the cell nucleus. We demonstrated that the rhodamine
      B-conjugated triglyceride is a promising new material to obtain versatile dye
      labeled nanocarriers presenting different chemical nature in their surfaces. 

PMID- 24936158
TI  - A new method to disperse CdS quantum dot-sensitized TiO2 nanotube arrays into
      P3HT:PCBM layer for the improvement of efficiency of inverted polymer solar
      cells.
AB  - We report that the efficiency of ITO/nc-TiO2/P3HT:PCBM/MoO3/Ag inverted polymer
      solar cells (PSCs) can be improved by dispersing CdS quantum dot (QD)-sensitized
      TiO2 nanotube arrays (TNTs) in poly (3-hexylthiophene) and [6,6]-phenyl-C61
      butyric acid methyl ester (P3HT:PCBM) layer. The CdS QDs are deposited on the
      TNTs by a chemical bath deposition method. The experimental results show that the
      CdS QD-sensitized TNTs (CdS/TNTs) do not only increase the light absorption of
      the P3HT:PCBM layer but also reduce the charge recombination in the P3HT:PCBM
      layer. The dependence of device performances on cycles of CdS deposition on the
      TNTs was investigated. A high power conversion efficiency (PCE) of 3.52% was
      achieved for the inverted PSCs with 20 cyclic depositions of CdS on TNTs, which
      showed a 34% increase compared to the ITO/nc-TiO2/P3HT:PCBM/MoO3/Ag device
      without the CdS/TNTs. The improved efficiency is attributed to the improved light
      absorbance and the reduced charge recombination in the active layer. 

PMID- 24936159
TI  - pH-responsive micelles based on (PCL)2(PDEA-b-PPEGMA)2 miktoarm polymer:
      controlled synthesis, characterization, and application as anticancer drug
      carrier.
AB  - Amphiphilic A2(BC)2 miktoarm star polymers [poly(epsilon-caprolactone)]2-[poly(2
      (diethylamino)ethyl methacrylate)-b- poly(poly(ethylene glycol) methyl ether
      methacrylate)]2 [(PCL)2(PDEA-b-PPEGMA)2] were developed by a combination of ring
      opening polymerization (ROP) and continuous activators regenerated by electron
      transfer atom transfer radical polymerization (ARGET ATRP). The critical micelle
      concentration (CMC) values were extremely low (0.0024 to 0.0043 mg/mL), depending
      on the architecture of the polymers. The self-assembled empty and doxorubicin
      (DOX)-loaded micelles were spherical in morphologies, and the average sizes were
      about 63 and 110 nm. The release of DOX at pH 5.0 was much faster than that at pH
      6.5 and pH 7.4. Moreover, DOX-loaded micelles could effectively inhibit the
      growth of cancer cells HepG2 with IC50 of 2.0 MUg/mL. Intracellular uptake
      demonstrated that DOX was delivered into the cells effectively after the cells
      were incubated with DOX-loaded micelles. Therefore, the pH-sensitive (PCL)2(PDEA
      b-PPEGMA)2 micelles could be a prospective candidate as anticancer drug carrier
      for hydrophobic drugs with sustained release behavior. 

PMID- 24936160
TI  - Silicon quantum dot superlattice solar cell structure including silicon
      nanocrystals in a photogeneration layer.
AB  - The solar cell structure of n-type poly-silicon/5-nm-diameter silicon
      nanocrystals embedded in an amorphous silicon oxycarbide matrix (30 layers)/p
      type hydrogenated amorphous silicon/Al electrode was fabricated on a quartz
      substrate. An open-circuit voltage and a fill factor of 518 mV and 0.51 in the
      solar cell were obtained, respectively. The absorption edge of the solar cell was
      1.49 eV, which corresponds to the optical bandgap of the silicon nanocrystal
      materials, suggesting that it is possible to fabricate the solar cells with
      silicon nanocrystal materials, whose bandgaps are wider than that of crystalline
      silicon. PACS: 85.35.Be; 84.60.Jt; 78.67.Bf.

PMID- 24936161
TI  - A sight on the current nanoparticle-based gene delivery vectors.
AB  - Nowadays, gene delivery for therapeutic objects is considered one of the most
      promising strategies to cure both the genetic and acquired diseases of human. The
      design of efficient gene delivery vectors possessing the high transfection
      efficiencies and low cytotoxicity is considered the major challenge for
      delivering a target gene to specific tissues or cells. On this base, the
      investigations on non-viral gene vectors with the ability to overcome
      physiological barriers are increasing. Among the non-viral vectors, nanoparticles
      showed remarkable properties regarding gene delivery such as the ability to
      target the specific tissue or cells, protect target gene against nuclease
      degradation, improve DNA stability, and increase the transformation efficiency or
      safety. This review attempts to represent a current nanoparticle based on its
      lipid, polymer, hybrid, and inorganic properties. Among them, hybrids, as
      efficient vectors, are utilized in gene delivery in terms of materials (synthetic
      or natural), design, and in vitro/in vivo transformation efficiency. 

PMID- 24936162
TI  - XPS, TDS, and AFM studies of surface chemistry and morphology of Ag-covered L-CVD
      SnO2 nanolayers.
AB  - This is well known that the selectivity and sensitivity of tin dioxide (SnO2)
      thin film sensors for the detection of low concentration of volatile sulfides
      such as H2S in air can be improved by small amount of Ag additives. In this paper
      we present the results of comparative X-ray photoelectron spectroscopy (XPS),
      thermal desorption spectroscopy (TDS), and atomic force microscopy (AFM) studies
      of the surface chemistry and morphology of SnO2 nanolayers obtained by laser
      enhanced chemical vapor deposition (L-CVD) additionally covered with 1 monolayer
      (ML) of Ag. For as deposited SnO2 nanolayers, a mixture of tin oxide (SnO) and
      tin dioxide (SnO2) with the [C]/[Sn] ratio of approximately 1.3 was observed.
      After dry air exposure, the [O]/[Sn] ratio slightly increased to approximately
      1.55. Moreover, an evident increasing of C contamination was observed with
      [C]/[Sn] ratio of approximately 3.5. After TDS experiment, the [O]/[Sn] ratio
      goes back to 1.3, whereas C contamination evidently decreases (by factor of 3).
      Simultaneously, the Ag concentration after air exposure and TDS experiment
      subsequently decreased (finally by factor of approximately 2), which was caused
      by the diffusion of Ag atoms into the subsurface layers related to the grain-type
      surface morphology of Ag-covered L-CVD SnO2 nanolayers, as confirmed by XPS ion
      depth profiling studies. The variation of surface chemistry of the Ag-covered L
      CVD SnO2 after air exposure observed by XPS was in a good correlation with the
      desorption of residual gases from these nanolayers observed in TDS experiments. 

PMID- 24936163
TI  - Effects of the alkylamine functionalization of graphene oxide on the properties
      of polystyrene nanocomposites.
AB  - Alkylamine-functionalized graphene oxides (FGOs) have superior dispersibility in
      low-polar solvents and, as a result, they interact with low-polar polymers such
      as polystyrene. In this work, the functionalization of graphene oxide using three
      types of alkylamines, octylamine (OA), dodecylamine (DDA), and hexadecylamine
      (HDA), was performed, and nanocomposites of polystyrene (PS) and FGOs were
      prepared via solution blending. Different dispersions of FGOs over PS were
      obtained for the three alkylamines, and the properties of the PS composites were
      influenced by the length of the alkylamine. A better thermal stability was
      observed with a longer chain length of the alkylamine. On the other hand,
      functionalization with the shortest chain length alkylamine resulted in the
      highest increase in the storage modulus (3,640 MPa, 140%) at a 10 wt.% loading of
      FGO. 

PMID- 24936164
TI  - Hydrothermal growth of TiO2 nanowire membranes sensitized with CdS quantum dots
      for the enhancement of photocatalytic performance.
AB  - In this paper, TiO2 nanowires (NWs) on Ti foils were prepared using a simple
      hydrothermal approach and annealing treatment. CdS quantum dots (QDs) were
      assembled onto the crystallized TiO2 NWs by sequential chemical bath deposition.
      Ultraviolet-visible absorption spectra showed that CdS adds bands in the visible
      to the TiO2 absorption and exhibited a broad absorption band in the visible
      region, which extended the scope of absorption spectrum and helped improve the
      photocatalytic degradation efficiency. The results of photocatalytic experiment
      revealed that CdS-TiO2 NWs possessed higher photocatalytic activities toward
      methyl orange than pure TiO2 nanowires. The degradation efficiency of 96.32%
      after ten cycles indicated that the as-prepared CdS-TiO2 composite exhibited
      excellent long-time recyclable ability and can be reused for the degradation of
      contaminants. 

PMID- 24936165
TI  - Simplified ZrTiO x -based RRAM cell structure with rectifying characteristics by
      integrating Ni/n + -Si diode.
AB  - A simplified one-diode one-resistor (1D1R) resistive switching memory cell that
      uses only four layers of TaN/ZrTiO x /Ni/n(+)-Si was proposed to suppress sneak
      current where TaN/ZrTiO x /Ni can be regarded as a resistive-switching random
      access memory (RRAM) device while Ni/n(+)-Si acts as an Schottky diode. This is
      the first RRAM cell structure that employs metal/semiconductor Schottky diode for
      current rectifying. The 1D1R cell exhibits bipolar switching behavior with
      SET/RESET voltage close to 1 V without requiring a forming process. More
      importantly, the cell shows tight resistance distribution for different states,
      significantly rectifying characteristics with forward/reverse current ratio
      higher than 10(3) and a resistance ratio larger than 10(3) between two states.
      Furthermore, the cell also displays desirable reliability performance in terms of
      long data retention time of up to 10(4) s and robust endurance of 10(5) cycles.
      Based on the promising characteristics, the four-layer 1D1R structure holds the
      great potential for next-generation nonvolatile memory technology. 

PMID- 24936166
TI  - Observation of linear and quadratic magnetic field-dependence of magneto
      photocurrents in InAs/GaSb superlattice.
AB  - We experimentally studied the magneto-photocurrents generated by direct interband
      transition in InAs/GaSb type II superlattice. By varying the magnetic field
      direction, we observed that an in-plane magnetic field induces a photocurrent
      linearly proportional to the magnetic field; however, a magnetic field tilted to
      the sample plane induces a photocurrent presenting quadratic magnetic field
      dependence. The magneto-photocurrents in both conditions are insensitive to the
      polarization state of the incident light. Theoretical models involving
      excitation, relaxation and Hall effect are utilized to explain the experimental
      results. 

PMID- 24936167
TI  - Disrupting KATP channels diminishes the estrogen-mediated protection in female
      mutant mice during ischemia-reperfusion.
AB  - BACKGROUND: Estrogen has been shown to mediate protection in female hearts
      against ischemia-reperfusion (I-R) stress. Composed by a Kir6.2 pore and an SUR2
      regulatory subunit, cardiac ATP-sensitive potassium channels (KATP) remain
      quiescent under normal physiological conditions but they are activated by stress
      stimuli to confer protection to the heart. It remains unclear whether KATP is a
      regulatory target of estrogen in the female-specific I-R signaling pathway. In
      this study, we aimed at delineating the molecular mechanism underlying estrogen
      modulation on KATP channel activity during I-R. MATERIALS AND METHODS: We
      employed KATP knockout mice in which SUR2 is disrupted (SUR2KO) to characterize
      their I-R response using an in vivo occlusion model. To test the protective
      effects of estrogen, female mice were ovariectomized and implanted with 17beta
      estradiol (E2) or placebo pellets (0.1 MUg/g/day, 21-day release) before
      receiving an I-R treatment. Comparative proteomic analyses were performed to
      assess pathway-level alterations between KO-IR and WT-IR hearts. RESULTS AND
      DISCUSSION: Echocardiographic results indicated that KO females were pre-disposed
      to cardiac dysfunction at baseline. The mutant mice were more susceptible to I-R
      stress by having bigger infarcts (46%) than WT controls (31%). The observation
      was confirmed using ovariectomized mice implanted with E2 or placebo. However,
      the estrogen-mediated protection was diminished in KO hearts. Expression studies
      showed that the SUR2 protein level, but not RNA level, was up-regulated in WT-IR
      mice relative to untreated controls possibly via PTMs. Our antibodies detected
      different glycosylated SUR2 receptor species after the PNGase F treatment,
      suggesting that SUR2 could be modified by N-glycosylation. We subsequently showed
      that E2 could further induce the formation of complex-glycosylated SUR2.
      Additional time-point experiments revealed that I-R hearts had increased levels
      of N-glycosylated SUR2; and DPM1, the first committed step enzyme in the N
      glycosylation pathway. Comparative proteomic profiling identified 41
      differentially altered protein hits between KO-IR and WT-IR mice encompassing
      those related to estrogen biosynthesis. CONCLUSIONS: Our findings suggest that
      KATP is likely a downstream regulatory target of estrogen and it is indispensable
      in female I-R signaling. Increasing SUR2 expression by N-glycosylation mediated
      by estrogen may be effective to enhance KATP channel subunit expression in I-R.

PMID- 24936168
TI  - Effectiveness of proactive and reactive services at the Swedish National Tobacco
      Quitline in a randomized trial.
AB  - BACKGROUND: The Swedish National Tobacco Quitline (SNTQ), which has both a
      proactive and a reactive service, has successfully provided tobacco cessation
      support since 1998. As there is a demand for an increase in national cessation
      support, and because the quitline works under funding constraints, it is crucial
      to identify the most clinically effective and cost-effective service. A
      randomized controlled trial was performed to compare the effectiveness of the
      high-intensity proactive service with the low-intensity reactive service at the
      SNTQ. METHODS: Those who called the SNTQ for smoking or tobacco cessation from
      February 2009 to September 2010 were randomized to proactive service (even dates)
      and reactive service (odd dates). Data were collected through postal
      questionnaires at baseline and after 12 months. Those who replied to the baseline
      questionnaire constituted the study base. Outcome measures were self-reported
      point prevalence and 6-month continuous abstinence at the 12-month follow-up.
      Intention-to-treat (ITT) and responder-only analyses were performed. RESULTS: The
      study base consisted of 586 persons, and 59% completed the 12-month follow-up.
      Neither ITT- nor responder-only analyses showed any differences in outcome
      between proactive and reactive service. Point prevalence was 27% and continuous
      abstinence was 21% in analyses treating non-responders as smokers, and 47% and
      35%, respectively, in responder-only analyses. CONCLUSION: Reactive service may
      be used as the standard procedure to optimize resource utilization at the SNTQ.
      However, further research is needed to assess effectiveness in different
      subgroups of clients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02085616.

PMID- 24936169
TI  - Higher blood glucose level associated with body mass index and gut microbiota in
      elderly people.
AB  - BACKGROUND: Some dominant bacterial divisions of the intestines have been linked
      to metabolic diseases such as overweight and diabetes. OBJECTIVE: A pilot study
      aimed to evaluate the relations between the culturable intestinal bacteria with
      body mass index (BMI) and some principal cellular and metabolic markers of blood
      in people older than 65. DESIGN: Altogether 38 generally healthy elderly people
      were recruited: ambulatory (n=19) and orthopedic surgery (n=19). Questionnaires
      on general health, anthropometric measurements, routine clinical and laboratory
      data, and quantitative composition of cultivable gut microbiota were performed.
      RESULTS: Blood glucose level was positively correlated with BMI (r=0.402;
      p=0.014). Higher blood glucose level had negative correlation with relative share
      of intestinal anaerobic bacteria such as bacteroides (r=-0.434; p=0.0076) and
      gram-positive anaerobic cocci (r=-0.364; p=0.027). In contrast, the relative
      share of bifidobacteria (r=0.383; p=0.019) and staphylococci (r=0.433; p=0.008)
      was positively correlated to blood glucose level. In elderly people, a higher
      blood glucose concentration was predicted by the reduction of the anaerobes'
      proportion (adj. sex, age, and BMI R(2)=0.192, p=0.028) and that of Bacteroides
      sp. (adj. R(2)=0.309, p=0.016). CONCLUSION: A tight interplay between increased
      BMI, level of blood glucose, and the reduced proportion of cultivable bacteroides
      is taking place in the gut microbiota of elderly people.

PMID- 24936170
TI  - Evaluating auditory stream segregation of SAM tone sequences by subjective and
      objective psychoacoustical tasks, and brain activity.
AB  - Auditory stream segregation refers to a segregated percept of signal streams with
      different acoustic features. Different approaches have been pursued in studies of
      stream segregation. In psychoacoustics, stream segregation has mostly been
      investigated with a subjective task asking the subjects to report their percept.
      Few studies have applied an objective task in which stream segregation is
      evaluated indirectly by determining thresholds for a percept that depends on
      whether auditory streams are segregated or not. Furthermore, both perceptual
      measures and physiological measures of brain activity have been employed but only
      little is known about their relation. How the results from different tasks and
      measures are related is evaluated in the present study using examples relying on
      the ABA- stimulation paradigm that apply the same stimuli. We presented A and B
      signals that were sinusoidally amplitude modulated (SAM) tones providing purely
      temporal, spectral or both types of cues to evaluate perceptual stream
      segregation and its physiological correlate. Which types of cues are most
      prominent was determined by the choice of carrier and modulation frequencies (f
      mod) of the signals. In the subjective task subjects reported their percept and
      in the objective task we measured their sensitivity for detecting time-shifts of
      B signals in an ABA- sequence. As a further measure of processes underlying
      stream segregation we employed functional magnetic resonance imaging (fMRI). SAM
      tone parameters were chosen to evoke an integrated (1-stream), a segregated (2
      stream), or an ambiguous percept by adjusting the f mod difference between A and
      B tones (Deltaf mod). The results of both psychoacoustical tasks are
      significantly correlated. BOLD responses in fMRI depend on Deltaf mod between A
      and B SAM tones. The effect of Deltaf mod, however, differs between auditory
      cortex and frontal regions suggesting differences in representation related to
      the degree of perceptual ambiguity of the sequences. 

PMID- 24936171
TI  - GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and
      clinical evidence.
AB  - The present paper summarizes the preclinical and clinical studies conducted to
      define the "anti-alcohol" pharmacological profile of the prototypic GABAB
      receptor agonist, baclofen, and its therapeutic potential for treatment of
      alcohol use disorder (AUD). Numerous studies have reported baclofen-induced
      suppression of alcohol drinking (including relapse- and binge-like drinking) and
      alcohol reinforcing, motivational, stimulating, and rewarding properties in
      rodents and monkeys. The majority of clinical surveys conducted to date-including
      case reports, retrospective chart reviews, and randomized placebo-controlled
      studies-suggest the ability of baclofen to suppress alcohol consumption, craving
      for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients.
      The recent identification of a positive allosteric modulatory binding site,
      together with the synthesis of in vivo effective ligands, represents a novel, and
      likely more favorable, option for pharmacological manipulations of the GABAB
      receptor. Accordingly, data collected to date suggest that positive allosteric
      modulators of the GABAB receptor reproduce several "anti-alcohol" effects of
      baclofen and display a higher therapeutic index (with larger separation-in terms
      of doses-between "anti-alcohol" effects and sedation). 

PMID- 24936172
TI  - The inflammatory molecules IL-1beta and HMGB1 can rapidly enhance focal seizure
      generation in a brain slice model of temporal lobe epilepsy.
AB  - Epilepsy is a neurological disorder characterized by a hyperexcitable brain
      tissue and unpredictable seizures, i.e., aberrant firing discharges in large
      neuronal populations. It is well established that proinflammatory cytokines, in
      addition to their canonical involvement in the immune response, have a crucial
      role in the mechanism of seizure generation. The purpose of the present study was
      to investigate the role of interleukin-1beta (IL-1beta) and high mobility group
      B1 (HMGB1) in the generation of seizure-like discharges using two models of focal
      epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges
      were evoked by either slice perfusion with low Mg(2+) and picrotoxin or with a
      double NMDA local stimulation in the presence of the proconvulsant 4-amino
      pyridine. The effects of IL-1beta or HMGB1 were evaluated by monitoring seizure
      discharge generation through laser scanning microscope imaging of Ca(2+) signals
      from neurons and astrocytes. In the picrotoxin model, we revealed that both
      cytokines increased the mean frequency of spontaneous ictal-like discharges,
      whereas only IL-1beta reduced the latency and prolonged the duration of the first
      ictal-like event. In the second model, a single NMDA pulse, per se ineffective,
      became successful when it was performed after IL-beta or HMGB1 local
      applications. These findings demonstrate that both IL-1beta and HMGB1 can rapidly
      lower focal ictal event threshold and strengthen the possibility that targeting
      these inflammatory pathways may represent an effective therapeutic strategy to
      prevent seizures. 

PMID- 24936173
TI  - Stress-induced plasticity of GABAergic inhibition.
AB  - GABAergic neurotransmission is highly plastic, undergoing dynamic alterations in
      response to changes in the environment, such as following both acute and chronic
      stress. Stress-induced plasticity of GABAergic inhibition is thought to
      contribute to changes in neuronal excitability associated with stress, which is
      particularly relevant for stress-related disorders and seizure susceptibility.
      Here we review the literature demonstrating several mechanisms altering GABAergic
      inhibition associated with stress, including brain region-specific alterations in
      GABAA receptor (GABAAR) subunit expression, changes in chloride homeostasis, and
      plasticity at GABAergic synapses. Alterations in the expression of specific
      GABAAR subunits have been documented in multiple brain regions associated with
      acute or chronic stress. In addition, recent work demonstrates stress-induced
      alterations in GABAergic inhibition resulting from plasticity in intracellular
      chloride levels. Acute and chronic stress-induced dephosphorylation and
      downregulation of the K(+)/Cl(-) co-transporter, KCC2, has been implicated in
      compromising GABAergic control of corticotropin-releasing hormone (CRH) neurons
      necessary for mounting the physiological response to stress. Acute stress also
      unmasks the capacity for both long-term potentiation and long-term depression, in
      distinct temporal windows, at GABAergic synapses on parvocellular neuroendocrine
      cells (PNCs) in the paraventricular nucleus (PVN) of the hypothalamus. This
      review highlights the complexity in the plasticity of GABAergic neurotransmission
      associated with stress and the relationship to neuronal excitability, including
      alterations in GABAAR expression, synaptic plasticity at GABAergic synapses, and
      changes in chloride homeostasis. 

PMID- 24936174
TI  - Empirical evidence for musical syntax processing? Computer simulations reveal the
      contribution of auditory short-term memory.
AB  - During the last decade, it has been argued that (1) music processing involves
      syntactic representations similar to those observed in language, and (2) that
      music and language share similar syntactic-like processes and neural resources.
      This claim is important for understanding the origin of music and language
      abilities and, furthermore, it has clinical implications. The Western musical
      system, however, is rooted in psychoacoustic properties of sound, and this is not
      the case for linguistic syntax. Accordingly, musical syntax processing could be
      parsimoniously understood as an emergent property of auditory memory rather than
      a property of abstract processing similar to linguistic processing. To support
      this view, we simulated numerous empirical studies that investigated the
      processing of harmonic structures, using a model based on the accumulation of
      sensory information in auditory memory. The simulations revealed that most of the
      musical syntax manipulations used with behavioral and neurophysiological methods
      as well as with developmental and cross-cultural approaches can be accounted for
      by the auditory memory model. This led us to question whether current research on
      musical syntax can really be compared with linguistic processing. Our simulation
      also raises methodological and theoretical challenges to study musical syntax
      while disentangling the confounded low-level sensory influences. In order to
      investigate syntactic abilities in music comparable to language, research should
      preferentially use musical material with structures that circumvent the tonal
      effect exerted by psychoacoustic properties of sounds. 

PMID- 24936177
TI  - Extending the mind: a review of ethnographies of neuroscience practice.
AB  - THIS PAPER REVIEWS ETHNOGRAPHIES OF NEUROSCIENCE LABORATORIES IN THE UNITED
      STATES AND EUROPE, ORGANIZING THEM INTO THREE MAIN SECTIONS: (1) descriptions of
      the capabilities and limitations of technologies used in neuroimaging
      laboratories to map "activity" or "function" onto structural models of the brain;
      (2) discussions of the "distributed" or "extended" mind in neuroscience practice;
      and (3) the implications of neuroscience research and the power of brain images
      outside the laboratory. I will try to show the importance of ethnographic work in
      such settings, and place this body of ethnographic work within its historical
      framework-such ethnographies largely emerged within the Decade of the Brain, as
      announced by former President of the United States George H. W. Bush in 1990. The
      main argument is that neuroscience research and the context within which it is
      taking place has changed since the 1990's-specifically with the launch of "big
      science" projects such as the Human Brain Project (HBP) in the European Union and
      the BRAIN initiative in the United States. There is an opportunity for more
      research into the institutional and politico-economic context within which
      neuroscience research is taking place, and for continued engagement between the
      social and biological sciences. 

PMID- 24936176
TI  - A unique memory process modulated by emotion underpins successful odor
      recognition and episodic retrieval in humans.
AB  - We behaviorally explore the link between olfaction, emotion and memory by testing
      the hypothesis that the emotion carried by odors facilitates the memory of
      specific unique events. To investigate this idea, we used a novel behavioral
      approach inspired by a paradigm developed by our team to study episodic memory in
      a controlled and as ecological as possible way in humans. The participants freely
      explored three unique and rich laboratory episodes; each episode consisted of
      three unfamiliar odors (What) positioned at three specific locations (Where)
      within a visual context (Which context). During the retrieval test, which
      occurred 24-72 h after the encoding, odors were used to trigger the retrieval of
      the complex episodes. The participants were proficient in recognizing the target
      odors among distractors and retrieving the visuospatial context in which they
      were encountered. The episodic nature of the task generated high and stable
      memory performances, which were accompanied by faster responses and slower and
      deeper breathing. Successful odor recognition and episodic memory were not
      related to differences in odor investigation at encoding. However, memory
      performances were influenced by the emotional content of the odors, regardless of
      odor valence, with both pleasant and unpleasant odors generating higher
      recognition and episodic retrieval than neutral odors. Finally, the present study
      also suggested that when the binding between the odors and the spatio-contextual
      features of the episode was successful, the odor recognition and the episodic
      retrieval collapsed into a unique memory process that began as soon as the
      participants smelled the odors. 

PMID- 24936175
TI  - Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes:
      pivotal role of pre- and post-synaptic 5-HT1A receptor expression.
AB  - Decreased serotonergic activity has been implicated in anxiety and major
      depression, and antidepressants directly or indirectly increase the long-term
      activity of the serotonin system. A key component of serotonin circuitry is the 5
      HT1A autoreceptor, which functions as the major somatodendritic autoreceptor to
      negatively regulate the "gain" of the serotonin system. In addition, 5-HT1A
      heteroreceptors are abundantly expressed post-synaptically in the prefrontal
      cortex (PFC), amygdala, and hippocampus to mediate serotonin actions on fear,
      anxiety, stress, and cognition. Importantly, in the PFC 5-HT1A heteroreceptors
      are expressed on at least two antagonist neuronal populations: excitatory
      pyramidal neurons and inhibitory interneurons. Rodent models implicate the 5-HT1A
      receptor in anxiety- and depression-like phenotypes with distinct roles for pre-
      and post-synaptic 5-HT1A receptors. In this review, we present a model of
      serotonin-PFC circuitry that integrates evidence from mouse genetic models of
      anxiety and depression involving knockout, suppression, over-expression, or
      mutation of genes of the serotonin system including 5-HT1A receptors. The model
      postulates that behavioral phenotype shifts as serotonin activity increases from
      none (depressed/aggressive not anxious) to low (anxious/depressed) to high
      (anxious, not depressed). We identify a set of conserved transcription factors
      including Deaf1, Freud-1/CC2D1A, Freud-2/CC2D1B and glucocorticoid receptors that
      may confer deleterious regional changes in 5-HT1A receptors in depression, and
      how future treatments could target these mechanisms. Further studies to
      specifically test the roles and regulation of pyramidal vs. interneuronal
      populations of 5-HT receptors are needed better understand the role of serotonin
      in anxiety and depression and to devise more effective targeted therapeutic
      approaches. 

PMID- 24936178
TI  - The neural correlates of regulating another person's emotions: an exploratory
      fMRI study.
AB  - Studies investigating the neurophysiological basis of intrapersonal emotion
      regulation (control of one's own emotional experience) report that the frontal
      cortex exerts a modulatory effect on limbic structures such as the amygdala and
      insula. However, no imaging study to date has examined the neurophysiological
      processes involved in interpersonal emotion regulation, where the goal is
      explicitly to regulate another person's emotion. Twenty healthy participants (10
      males) underwent fMRI while regulating their own or another person's emotions.
      Intrapersonal and interpersonal emotion regulation tasks recruited an overlapping
      network of brain regions including bilateral lateral frontal cortex, pre
      supplementary motor area, and left temporo-parietal junction. Activations unique
      to the interpersonal condition suggest that both affective (emotional simulation)
      and cognitive (mentalizing) aspects of empathy may be involved in the process of
      interpersonal emotion regulation. These findings provide an initial insight into
      the neural correlates of regulating another person's emotions and may be relevant
      to understanding mental health issues that involve problems with social
      interaction. 

PMID- 24936179
TI  - Neurocognitive profiles of learning disabled children with neurofibromatosis type
      1.
AB  - Neurofibromatosis 1 (NF1) is a genetic condition generally associated with
      intellectual deficiency and learning disabilities. Although there have been
      groundbreaking advances in the understanding of the molecular, cellular, and
      neural systems underlying learning deficits associated to NF1 in animal models,
      much remains to be learned about the spectrum of neurocognitive phenotype
      associated with the NF1 clinical syndrome. In the present study, 32 children with
      NF1 ranging from 7 to 14 years were evaluated with neurocognitive tests dedicated
      to assess basic capacities which are involved in reading and mathematical
      achievement. Deficits in lexical and phonological strategies and poor number
      facts retrieval were found underlying reading and arithmetic disorders,
      respectively. Additionally, efficiencies in lexical/phonological strategies and
      mental arithmetic were significant predictors of individual differences in
      reading attainment and math. However, deficits in core numeric capacities were
      not found in the sample, suggesting that it is not responsible for calculation
      dysfluency. The estimated prevalence of Developmental Dyscalculia was 18.8%, and
      the male:female ratio was 5:1. On the other hand, the prevalence of Developmental
      Dyslexia was almost 3 times as high (50%), and no gender differences were found
      (male: female ratio = 1:1). This study offers new evidence to the neurocognitive
      phenotype of NF1 contributing to an in depth understanding of this condition, but
      also to possible treatments for the cognitive deficits associated with NF1. 

PMID- 24936180
TI  - Working memory capacity as a moderator of load-related frontal midline theta
      variability in Sternberg task.
AB  - The aim of this study was to investigate the relationship between working memory
      capacity (WMC) and frontal theta response to memory load in Sternberg task. We
      show that oscillatory activity in the theta band (4-6 Hz) related to Sternberg
      task performance may differentiate people characterized by high and low WMC.
      Specifically, there is a linear increase of frontal midline (FM) theta power with
      load, however, only in the high WMC group. Furthermore, a positive linear
      relationship was found between WMC (operation span task score) and average FM
      theta power increase from lower to higher loads which was not present at other
      scalp locations. The distinct patterns of high and low WMC individual's FM theta
      response to memory load seem to support the assumption that theta activity during
      maintenance reflects not only the amount of information stored, but also the
      effort it takes to remember them and the efficiency of involved neural processes.
      This contributes to perceiving FM theta as an individual trait which can reflect
      individual working memory mechanism efficiency. 

PMID- 24936181
TI  - Missing and delayed auditory responses in young and older children with autism
      spectrum disorders.
AB  - BACKGROUND: The development of left and right superior temporal gyrus (STG) 50 ms
      (M50) and 100 ms (M100) auditory responses in typically developing (TD) children
      and in children with autism spectrum disorder (ASD) was examined. Reflecting
      differential development of primary/secondary auditory areas and supporting
      previous studies, it was hypothesized that whereas left and right M50 STG
      responses would be observed equally often in younger and older children, left and
      right M100 STG responses would more often be absent in younger than older
      children. In ASD, delayed neurodevelopment would be indicated via the observation
      of a greater proportion of ASD than TD subjects showing missing M100 but not M50
      responses in both age groups. Missing M100 responses would be observed primarily
      in children with ASD with language impairment (ASD + LI) (and perhaps
      concomitantly lower general cognitive abilities). METHODS: Thirty-five TD
      controls, 63 ASD without language impairment (ASD - LI), and 38 ASD + LI were
      recruited. Binaural tones were presented. The presence or absence of a STG M50
      and M100 was scored. Subjects were grouped into younger (6-10 years old) and
      older groups (11-15 years old). RESULTS: Although M50 responses were observed
      equally often in older and younger subjects and equally often in TD and ASD, left
      and right M50 responses were delayed in ASD - LI and ASD + LI. Group comparisons
      showed that in younger subjects M100 responses were observed more often in TD
      than ASD + LI (90 versus 66%, p = 0.04), with no differences between TD and ASD -
      LI (90 versus 76%, p = 0.14) or between ASD - LI and ASD + LI (76 versus 66%, p =
      0.53). In older subjects, whereas no differences were observed between TD and ASD
      + LI, responses were observed more often in ASD - LI than ASD + LI. Findings were
      similar when splitting the ASD group into lower- and higher-cognitive functioning
      groups. CONCLUSION: Although present in all groups, M50 responses were delayed in
      ASD. Examining the TD data, findings indicated that by 11 years, a right M100
      should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus,
      by 11 years, lack of a left and especially right M100 offers neurobiological
      insight into sensory processing that may underlie language or cognitive
      impairment.

PMID- 24936182
TI  - On how correlations between excitatory and inhibitory synaptic inputs maximize
      the information rate of neuronal firing.
AB  - Cortical neurons receive barrages of excitatory and inhibitory inputs which are
      not independent, as network structure and synaptic kinetics impose statistical
      correlations. Experiments in vitro and in vivo have demonstrated correlations
      between inhibitory and excitatory synaptic inputs in which inhibition lags behind
      excitation in cortical neurons. This delay arises in feed-forward inhibition
      (FFI) circuits and ensures that coincident excitation and inhibition do not
      preclude neuronal firing. Conversely, inhibition that is too delayed broadens
      neuronal integration times, thereby diminishing spike-time precision and
      increasing the firing frequency. This led us to hypothesize that the correlation
      between excitatory and inhibitory synaptic inputs modulates the encoding of
      information of neural spike trains. We tested this hypothesis by investigating
      the effect of such correlations on the information rate (IR) of spike trains
      using the Hodgkin-Huxley model in which both synaptic and membrane conductances
      are stochastic. We investigated two different synaptic input regimes: balanced
      synaptic conductances and balanced currents. Our results show that correlations
      arising from the synaptic kinetics, tau, and millisecond lags, delta, of
      inhibition relative to excitation strongly affect the IR of spike trains. In the
      regime of balanced synaptic currents, for short time lags (delta ~ 1 ms) there is
      an optimal tau that maximizes the IR of the postsynaptic spike train. Given the
      short time scales for monosynaptic inhibitory lags and synaptic decay kinetics
      reported in cortical neurons under physiological contexts, we propose that FFI in
      cortical circuits is poised to maximize the rate of information transfer between
      cortical neurons. Our results also provide a possible explanation for how certain
      drugs and genetic mutations affecting the synaptic kinetics can deteriorate
      information processing in the brain. 

PMID- 24936183
TI  - Identifying endophenotypes of autism: a multivariate approach.
AB  - The existence of an endophenotype of autism spectrum condition (ASC) has been
      recently suggested by several commentators. It can be estimated by finding
      differences between controls and people with ASC that are also present when
      comparing controls and the unaffected siblings of ASC individuals. In this work,
      we used a multivariate methodology applied on magnetic resonance images to look
      for such differences. The proposed procedure consists of combining a searchlight
      approach and a support vector machine classifier to identify the differences
      between three groups of participants in pairwise comparisons: controls, people
      with ASC and their unaffected siblings. Then we compared those differences
      selecting spatially collocated as candidate endophenotypes of ASC. 

PMID- 24936184
TI  - Salivary DJ-1 could be an indicator of Parkinson's disease progression.
AB  - OBJECTIVE: The goal of the current investigation was to explore whether salivary
      DJ-1 could be a potential biomarker for monitoring disease progression in
      Parkinson's disease (PD) by evaluating the association between salivary DJ-1
      concentrations and nigrostriatal dopaminergic function. METHODS: First, in 74
      patients with PD and 12 age-matched normal controls, single photon emission
      computed tomography (SPECT) imaging with labeled dopamine transporters (DAT)
      ((99m)Tc-TRODAT-1), which has been used for measuring DAT density in PD was
      prformed. Then, the DJ-1 level in their saliva was analyzed by quantitative and
      sensitive Luminex assay and compared to caudate or putamen DAT density. Finally,
      based on the above, our cross-section study was carried out in 376 research
      volunteers (285 patients with PD and 91 healthy controls) to measure salivary DJ
      1 level. RESULTS: From our analysis, we found a correlation between salivary
      concentration of DJ-1 and putamen nucleus uptake of (99m)Tc-TRODAT-1 in the PD
      group. Although salivary DJ-1 levels were not affected by UPDRS scores, gender,
      age, and pharmacotherapy, DJ-1 levels in H&Y 4 stage of PD were higher than those
      in H&Y 1-3 stage as well as those in healthy controls. Salivary DJ-1 also
      decreased significantly in mixed type PD patients compared to the tremor-dominant
      type (TDT) and akinetic-rigid dominant type (ARDT) PD patients. CONCLUSIONS:
      According to the investigation in a large cohort, we reported for the first time
      the prognostic potential of the salivary DJ-1 as a biomarker for evaluating
      nigrostriatal dopaminergic function in PD.

PMID- 24936185
TI  - Delayed plastic responses to anodal tDCS in older adults.
AB  - Despite the abundance of research reporting the neurophysiological and behavioral
      effects of transcranial direct current stimulation (tDCS) in healthy young adults
      and clinical populations, the extent of potential neuroplastic changes induced by
      tDCS in healthy older adults is not well understood. The present study compared
      the extent and time course of anodal tDCS-induced plastic changes in primary
      motor cortex (M1) in young and older adults. Furthermore, as it has been
      suggested that neuroplasticity and associated learning depends on the brain
      derived neurotrophic factor (BDNF) gene polymorphisms, we also assessed the
      impact of BDNF polymorphism on these effects. Corticospinal excitability was
      examined using transcranial magnetic stimulation before and following (0, 10, 20,
      30 min) anodal tDCS (30 min, 1 mA) or sham in young and older adults. While the
      overall extent of increases in corticospinal excitability induced by anodal tDCS
      did not vary reliably between young and older adults, older adults exhibited a
      delayed response; the largest increase in corticospinal excitability occurred 30
      min following stimulation for older adults, but immediately post-stimulation for
      the young group. BDNF genotype did not result in significant differences in the
      observed excitability increases for either age group. The present study suggests
      that tDCS-induced plastic changes are delayed as a result of healthy aging, but
      that the overall efficacy of the plasticity mechanism remains unaffected. 

PMID- 24936186
TI  - Cellular stress response, redox status, and vitagenes in glaucoma: a systemic
      oxidant disorder linked to Alzheimer's disease.
AB  - Amyloid deposits, constituted of amyloid beta (Abeta) aggregates, are a
      characteristic feature of several neurodegenerative diseases, such as
      Alzheimer's, mild cognitive impairment and Parkinson's disease. They also have
      been recently implicated in the pathogenesis of retinal damage, as well as age
      related macular degeneration and glaucoma. Glaucoma is a progressive optic
      neuropathy characterized by gradual degeneration of neuronal tissue due to
      retinal ganglion cell loss, associated to visual field loss over time resulting
      in irreversible blindness. Accumulation of Abeta characterizes glaucoma as a
      protein misfolding disease, suggesting a pathogenic role for oxidative stress in
      the pathogenesis of retinal degenerative damage associated to glaucoma. There is
      a growing body of evidence demonstrating a link between Alzheimer's disease and
      glaucoma. Further, several heat shock proteins (HSPs) members have been
      implicated both in neurodegenerative diseases and glaucomatous apoptosis. To
      maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively
      to preserve cell survival under condition of stress. Vitagenes encode for
      sirtuin, thioredoxin and HSPs. The present study was designed to investigate
      cellular stress response mechanisms in the blood of patients with glaucoma,
      compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as
      well as F2-isoprostanes were significantly higher in the blood of patients with
      glaucoma than in controls. Furthermore, in the same experimental group increased
      expression of Trx and sirtuin 1 were measured. Our results sustain the importance
      of redox homeostasis disruption in the pathogenesis of glaucoma and highlights
      the opportunity that new therapies that prevents neurodegeneration through non
      immunomodulatory mechanisms might be synergistically associated with current
      glaucoma therapies, thus unraveling important targets for novel cytoprotective
      strategies. 

PMID- 24936187
TI  - Is a low level of free thyroxine in the maternal circulation associated with
      altered endothelial function in gestational diabetes?
AB  - Synthesis of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3), in the
      human fetus starts from 17 to 19th weeks of gestation. Despite the majority of
      normal pregnant women reaching adequate levels of circulating thyroid hormones,
      in some cases, women with normal pregnancies have low level of free T4 during
      first trimester of pregnancy, suggesting that T4 action may be compromised in
      those women and their fetuses. In addition, pathological low levels of thyroid
      hormones are detected in isolated maternal hypothyroxemia (IMH) and clinical
      hypothyroidism. Nevertheless, human placenta regulates T3/T4 concentration in the
      fetal circulation by modulating the expression and activity of both thyroid
      hormone transporters (THT) and deiodinases. Then, placenta can control the
      availability of T3/T4 in the feto-placental circulation, and therefore may
      generate an adaptive response in cases where the mother courses with low levels
      of T4. In addition, T3/T4 might control vascular response in the placenta, in
      particularly endothelial cells may induce the synthesis and release of
      vasodilators such as nitric oxide (NO) or vasoconstrictors such as endothelin-1
      mediated by these hormones. On the other hand, low levels of T4 have been
      associated with increase in gestational diabetes (GD) markers. Since GD is
      associated with impaired placental vascular function characterized by increased
      NO synthesis in placental arteries and veins, as well as elevated placental
      angiogenesis, it is unknown whether reduced T4 level at the maternal circulation
      could result in an altered placental endothelial function during GD. In this
      review, we analyze available information regarding thyroid hormones and
      endothelial dysfunction in GD; and propose that low maternal levels of T4
      observed in GD may be compensated by increased placental availability of T3/T4
      via elevation in the activity of THT and/or reduction in deiodinases in the feto
      placental circulation. 

PMID- 24936188
TI  - Structural considerations of vitamin D signaling.
AB  - Crystal structures represent the static picture in the life of a molecule giving
      a sneak preview what it might be in reality. Hence, it is very hard to
      extrapolate from these photos toward dynamic processes such as transcriptional
      regulation. Mechanistically VDR may be considered as molecular machine able to
      perform ligand-, DNA- and protein recognition, and interaction in a multi-task
      manner. Taking this into account the functional net effect will be the
      combination of all these processes. The long awaited answer to explain the
      differences in physiological effects for various ligands was one of the biggest
      disappointment that crystal structures provided since no substantial distinction
      could be made for the conformation of the active VDR-ligand complexes. This may
      have come from the limitation on the complexity of the available ligand-VDR
      structures. The recent studies with full length VDR-RXRalpha showed somewhat more
      comprehensive perspective for the 3D organization and possible function of the
      VDR-RXRalpha-cofactor complex. In addition to in vitro approaches, also
      computational tools had been introduced with the aim to get understanding on the
      mechanic and dynamic properties of the VDR complexes with some success. Using
      these methods and based on measurable descriptors such as pocket size and
      positions of side chains it is possible to note subtle differences between the
      structures. The meaning of these differences has not been fully understood yet
      but the possibility of a "butterfly effect" may have more extreme consequences in
      terms of VDR signaling. In this review, the three functional aspects (ligand-,
      DNA- and protein recognition, and binding) will be discussed with respect to
      available data as well as possible implication and questions that may be
      important to address in the future. 

PMID- 24936190
TI  - Score-based tests of measurement invariance: use in practice.
AB  - In this paper, we consider a family of recently-proposed measurement invariance
      tests that are based on the scores of a fitted model. This family can be used to
      test for measurement invariance w.r.t. a continuous auxiliary variable, without
      pre-specification of subgroups. Moreover, the family can be used when one wishes
      to test for measurement invariance w.r.t. an ordinal auxiliary variable, yielding
      test statistics that are sensitive to violations that are monotonically related
      to the ordinal variable (and less sensitive to non-monotonic violations). The
      paper is specifically aimed at potential users of the tests who may wish to know
      (1) how the tests can be employed for their data, and (2) whether the tests can
      accurately identify specific models parameters that violate measurement
      invariance (possibly in the presence of model misspecification). After providing
      an overview of the tests, we illustrate their general use via the R packages
      lavaan and strucchange. We then describe two novel simulations that provide
      evidence of the tests' practical abilities. As a whole, the paper provides
      researchers with the tools and knowledge needed to apply these tests to general
      measurement invariance scenarios. 

PMID- 24936189
TI  - Elucidating the molecular bases of epigenetic inheritance in non-model
      invertebrates: the case of the root-knot nematode Meloidogyne incognita.
AB  - Root-knot nematodes of the genus Meloidogyne are biotrophic plant parasites that
      exhibit different life cycles and reproduction modes, ranging from classical
      amphimixis to obligatory mitotic parthenogenesis (apomixis), depending on the
      species. Meloidogyne incognita, an apomictic species, exhibits a worldwide
      distribution and a wide host range affecting more than 3000 plant species.
      Furthermore, evidences suggest that apomixis does not prevent M. incognita from
      adapting to its environment in contrast to what is expected from mitotic
      parthenogenesis that should theoretically produce clonal progenies. This raises
      questions about mechanisms of genome plasticity leading to genetic variation and
      adaptive evolution in apomictic animals. We reasoned that epigenetic mechanisms
      might in part be responsible for the generation of phenotypic variants that
      provide potential for rapid adaptation. We established therefore a pipeline to
      investigate the principal carriers of epigenetic information, DNA methylation and
      post-translational histone modifications. Even if M. incognita possesses the
      epigenetic machinery i.e., chromatin modifying enzymes, 5-methyl-cytosine and 5
      hydroxy-methyl-cytosine content is absent or very weak. In contrast, we
      demonstrated that the canonical histone modifications are present and chromatin
      shows typical nucleosome structure. This work is the first characterization of
      carriers of epigenetic information in M. incognita and constitutes a preamble to
      further investigate if M. incognita development and its adaptation to plant hosts
      are under epigenetic control. Our pipeline should allow performing similar types
      of studies in any non-model organism. 

PMID- 24936191
TI  - Embodied affectivity: on moving and being moved.
AB  - There is a growing body of research indicating that bodily sensation and behavior
      strongly influences one's emotional reaction toward certain situations or
      objects. On this background, a framework model of embodied affectivity is
      suggested: we regard emotions as resulting from the circular interaction between
      affective qualities or affordances in the environment and the subject's bodily
      resonance, be it in the form of sensations, postures, expressive movements or
      movement tendencies. Motion and emotion are thus intrinsically connected: one is
      moved by movement (perception; impression; affection) and moved to move (action;
      expression; e-motion). Through its resonance, the body functions as a medium of
      emotional perception: it colors or charges self-experience and the environment
      with affective valences while it remains itself in the background of one's own
      awareness. This model is then applied to emotional social understanding or
      interaffectivity which is regarded as an intertwinement of two cycles of embodied
      affectivity, thus continuously modifying each partner's affective affordances and
      bodily resonance. We conclude with considerations of how embodied affectivity is
      altered in psychopathology and can be addressed in psychotherapy of the embodied
      self. 

PMID- 24936192
TI  - Changing the game: exploring infants' participation in early play routines.
AB  - Play has proved to have a central role in children's development, most notably in
      rule learning (Piaget, 1965; Sutton-Smith, 1979) and negotiation of roles and
      goals (Garvey, 1974; Bruner et al., 1976). Yet very little research has been done
      on early play. The present study focuses on early social games, i.e., vocal
      kinetic play routines that mothers use to interact with infants from very early
      on. We explored 3-month-old infants and their mothers performing a routine game
      first in the usual way, then in two violated conditions: without gestures and
      without sound. The aim of the study is to investigate infants' participation and
      expectations in the game and whether this participation is affected by changes in
      the multimodal format of the game. Infants' facial expressions, gaze, and body
      movements were coded to measure levels of engagement and affective state across
      the three conditions. Results showed a significant decrease in Limbs Movements
      and expressions of Positive Affect, an increase in Gaze Away and in Stunned
      Expression when the game structure was violated. These results indicate that the
      violated game conditions were experienced as less engaging, either because of an
      unexpected break in the established joint routine, or simply because they were
      weaker versions of the same game. Overall, our results suggest that structured,
      multimodal play routines may constitute interactional contexts that only work as
      integrated units of auditory and motor resources, representing early
      communicative contexts which prepare the ground for later, more complex
      multimodal interactions, such as verbal exchanges. 

PMID- 24936194
TI  - Increasing interpersonal trust through divergent thinking.
AB  - Interpersonal trust is an essential ingredient of many social relationships but
      how stable is it actually, and how is it controlled? There is evidence that the
      degree of trust into others might be rather volatile and can be affected by
      manipulations like drawing attention to personal interdependence or independence.
      Here we investigated whether the degree of interpersonal trust can be biased by
      inducing either a more integrative or a more focused/exclusive cognitive control
      mode by means of a creativity task requiring divergent or convergent thinking,
      respectively. Participants then performed the trust game, which provides an index
      of interpersonal trust by assessing the money units one participant (the trustor)
      transfers to another (the trustee). As expected, trustors transferred
      significantly more money to trustees after engaging in divergent thinking as
      compared to convergent thinking. This observation provides support for the idea
      that interpersonal trust is controlled by domain-general (i.e., not socially
      dedicated) cognitive states. 

PMID- 24936193
TI  - The role of alpha-7 nicotinic receptors in food intake behaviors.
AB  - Nicotine alters appetite and energy expenditure, leading to changes in body
      weight. While the exact mechanisms underlying these effects are not fully
      established, both central and peripheral involvement of the alpha-7 nicotinic
      acetylcholine receptor (alpha7nAChR) has been suggested. Centrally, the
      alpha7nAChR modulates activity of hypothalamic neurons involved in food intake
      regulation, including proopiomelanocortin and neuropeptide Y. alpha7nAChRs also
      modulate glutamatergic and dopaminergic systems controlling reward processes that
      affect food intake. Additionally, alpha7nAChRs are important peripheral mediators
      of chronic inflammation, a key contributor to health problems in obesity. This
      review focuses on nicotinic cholinergic effects on eating behaviors, specifically
      those involving the alpha7nAChR, with the hypothesis that alpha7nAChR agonism
      leads to appetite suppression. Recent studies are highlighted that identify links
      between alpha7nAChR expression and obesity, insulin resistance, and diabetes and
      describe early findings showing an alpha7nAChR agonist to be associated with
      reduced weight gain in a mouse model of diabetes. Given these effects, the
      alpha7nAChR may be a useful therapeutic target for strategies to treat and manage
      obesity. 

PMID- 24936195
TI  - The integration hypothesis of human language evolution and the nature of
      contemporary languages.
AB  - How human language arose is a mystery in the evolution of Homo sapiens. Miyagawa
      et al. (2013) put forward a proposal, which we will call the Integration
      Hypothesis of human language evolution, that holds that human language is
      composed of two components, E for expressive, and L for lexical. Each component
      has an antecedent in nature: E as found, for example, in birdsong, and L in, for
      example, the alarm calls of monkeys. E and L integrated uniquely in humans to
      give rise to language. A challenge to the Integration Hypothesis is that while
      these non-human systems are finite-state in nature, human language is known to
      require characterization by a non-finite state grammar. Our claim is that E and
      L, taken separately, are in fact finite-state; when a grammatical process crosses
      the boundary between E and L, it gives rise to the non-finite state character of
      human language. We provide empirical evidence for the Integration Hypothesis by
      showing that certain processes found in contemporary languages that have been
      characterized as non-finite state in nature can in fact be shown to be finite
      state. We also speculate on how human language actually arose in evolution
      through the lens of the Integration Hypothesis. 

PMID- 24936196
TI  - Glucose and the injured brain-monitored in the neurointensive care unit.
AB  - Brain has a continuous demand for energy that is met by oxidative metabolism of
      oxygen and glucose. This demand is compromised in the injured brain and if the
      inadequate supply persists it will lead to permanent tissue damage. Zero values
      of cerebral glucose have been associated with infarction and poor neurological
      outcome. Furthermore, hyperglycemia is common in patients with neurological
      insults and associated with poor outcome. Intensive insulin therapy (IIT) to
      control blood glucose has been suggested and used in neurointensive care with
      conflicting results. This review covers the studies reporting on monitoring of
      cerebral glucose with microdialysis in patients with traumatic brain injury
      (TBI), subarachnoid hemorrhage (SAH) and ischemic stroke. Studies investigating
      IIT are also discussed. Available data suggest that low cerebral glucose in
      patients with TBI and SAH provides valuable information on development of
      secondary ischemia and has been correlated with worse outcome. There is also
      indication that the location of the catheter is important for correlation between
      plasma and brain glucose. In conclusion considering catheter location, monitoring
      of brain glucose in the neurointensive care not only provides information on
      imminent secondary ischemia it also reveals the effect of peripheral treatment on
      the injured brain. 

PMID- 24936197
TI  - Recovery from emotion recognition impairment after temporal lobectomy.
AB  - Mesial temporal lobe epilepsy (MTLE) can be associated with emotion recognition
      impairment that can be particularly severe in patients with early onset seizures
      (1-3). Whereas, there is growing evidence that memory and language can improve in
      seizure-free patients after anterior temporal lobectomy (ATL) (4), the effects of
      surgery on emotional processing are still unknown. We used functional magnetic
      resonance imaging (fMRI) to investigate short-term reorganization of networks
      engaged in facial emotion recognition in MTLE patients. Behavioral and fMRI data
      were collected from six patients before and after ATL. During the fMRI scan,
      patients were asked to make a gender decision on fearful and neutral faces.
      Behavioral data demonstrated that two patients with early onset right MTLE were
      impaired in fear recognition while fMRI results showed they lacked specific
      activations for fearful faces. Post-ATL behavioral data showed improved emotion
      recognition ability, while fMRI demonstrated the recruitment of a functional
      network for fearful face processing. Our results suggest that ATL elicited brain
      plasticity mechanisms allowing behavioral and fMRI improvement in emotion
      recognition. 

PMID- 24936200
TI  - Parasites in algae mass culture.
AB  - Parasites are now known to be ubiquitous across biological systems and can play
      an important role in modulating algal populations. However, there is a lack of
      extensive information on their role in artificial ecosystems such as algal
      production ponds and photobioreactors. Parasites have been implicated in the
      demise of algal blooms. Because individual mass culture systems often tend to be
      unialgal and a select few algal species are in wide scale application, there is
      an increased potential for parasites to have a devastating effect on commercial
      scale monoculture. As commercial algal production continues to expand with a
      widening variety of applications, including biofuel, food and pharmaceuticals,
      the parasites associated with algae will become of greater interest and potential
      economic impact. A number of important algal parasites have been identified in
      algal mass culture systems in the last few years and this number is sure to grow
      as the number of commercial algae ventures increases. Here, we review the
      research that has identified and characterized parasites infecting mass
      cultivated algae, the techniques being proposed and or developed to control them,
      and the potential impact of parasites on the future of the algal biomass
      industry. 

PMID- 24936198
TI  - Mesenchymal stem cell-based treatment for microvascular and secondary
      complications of diabetes mellitus.
AB  - The worldwide increase in the prevalence of Diabetes mellitus (DM) has
      highlighted the need for increased research efforts into treatment options for
      both the disease itself and its associated complications. In recent years,
      mesenchymal stromal cells (MSCs) have been highlighted as a new emerging
      regenerative therapy due to their multipotency but also due to their paracrine
      secretion of angiogenic factors, cytokines, and immunomodulatory substances. This
      review focuses on the potential use of MSCs as a regenerative medicine in
      microvascular and secondary complications of DM and will discuss the challenges
      and future prospects of MSCs as a regenerative therapy in this field. MSCs are
      believed to have an important role in tissue repair. Evidence in recent years has
      demonstrated that MSCs have potent immunomodulatory functions resulting in active
      suppression of various components of the host immune response. MSCs may also have
      glucose lowering properties providing another attractive and unique feature of
      this therapeutic approach. Through a combination of the above characteristics,
      MSCs have been shown to exert beneficial effects in pre-clinical models of
      diabetic complications prompting initial clinical studies in diabetic wound
      healing and nephropathy. Challenges that remain in the clinical translation of
      MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery,
      homing of these cells to tissues of interest with high efficiency, clinically
      meaningful engraftment, and challenges with cell manufacture. An issue of added
      importance is whether an autologous or allogeneic approach will be used. In
      summary, MSC administration has significant potential in the treatment of
      diabetic microvascular and secondary complications but challenges remain in terms
      of engraftment, persistence, tissue targeting, and cell manufacture. 

PMID- 24936199
TI  - CD8 T-cell-mediated protection against liver-stage malaria: lessons from a mouse
      model.
AB  - Malaria is a major global health problem, with severe mortality in children
      living in sub-Saharan Africa, and there is currently no licensed, effective
      vaccine. However, vaccine-induced protection from Plasmodium infection, the
      causative agent of malaria, was established for humans in small clinical trials
      and for rodents in the 1960s. Soon after, a critical role for memory CD8 T cells
      in vaccine-induced protection against Plasmodium liver-stage infection was
      established in rodent models and is assumed to apply to humans. However, these
      seminal early studies have led to only modest advances over the ensuing years in
      our understanding the basic features of memory CD8 T cells required for
      protection against liver-stage Plasmodium infection, an issue which has likely
      impeded the development of effective vaccines for humans. Given the ethical and
      practical limitations in gaining mechanistic insight from human vaccine and
      challenge studies, animal models still have an important role in dissecting the
      basic parameters underlying memory CD8 T-cell immunity to Plasmodium. Here, we
      will highlight recent data from our own work in the mouse model of Plasmodium
      infection that identify quantitative and qualitative features of protective
      memory CD8 T-cell responses. Finally, these lessons will be discussed in the
      context of recent findings from clinical trials of vaccine-induced protection in
      controlled human challenge models. 

PMID- 24936201
TI  - Analysis of MreB interactors in Chlamydia reveals a RodZ homolog but fails to
      detect an interaction with MraY.
AB  - Chlamydia is an obligate intracellular bacterial pathogen that has significantly
      reduced its genome in adapting to the intracellular environment. One class of
      genes for which the bacterium has few annotated examples is cell division, and
      Chlamydia lacks FtsZ, a central coordinator of the division apparatus. We have
      previously implicated MreB as a potential substitute for FtsZ in Chlamydia
      (Ouellette et al., 2012). Thus, to identify new chlamydial cell division
      components, we searched for proteins that interacted with MreB. We performed a
      small-scale screen using a Gateway(r) compatible version of the Bacterial
      Adenylate Cyclase Two Hybrid (BACTH) system, BACTHGW, to detect proteins
      interacting with chlamydial MreB and identified a RodZ (YfgA) homolog. The
      chlamydial RodZ aligns well with the cytoplasmic domain of E. coli RodZ but lacks
      the periplasmic domain that is dispensable for rod cell shape maintenance in E.
      coli. The expression pattern of yfgA/rodZ was similar to that of mreB and ftsI,
      suggesting that these genes may operate in a common functional pathway. The
      chlamydial RodZ correctly localized to the membrane of E. coli but was unable to
      complement an E. coli rodZ mutant strain, likely because of the inability of
      chlamydial RodZ to interact with the native E. coli MreB. Finally, we also tested
      whether chlamydial MreB could interact with MraY, as suggested by Gaballah et al.
      (2011). However, we did not detect an interaction between these proteins even
      when using an implementation of the BACTH system to allow native orientation of
      the N- and C-termini of MraY in the periplasm. Thus, further work will be needed
      to establish this proposed interaction. In sum, we have added to the repertoire
      of potential cell division proteins of Chlamydia. 

PMID- 24936202
TI  - Building the crops of tomorrow: advantages of symbiont-based approaches to
      improving abiotic stress tolerance.
AB  - The exponential growth in world population is feeding a steadily increasing
      global need for arable farmland, a resource that is already in high demand. This
      trend has led to increased farming on subprime arid and semi-arid lands, where
      limited availability of water and a host of environmental stresses often severely
      reduce crop productivity. The conventional approach to mitigating the abiotic
      stresses associated with arid climes is to breed for stress-tolerant cultivars, a
      time and labor intensive venture that often neglects the complex ecological
      context of the soil environment in which the crop is grown. In recent years,
      studies have attempted to identify microbial symbionts capable of conferring the
      same stress-tolerance to their plant hosts, and new developments in genomic
      technologies have greatly facilitated such research. Here, we highlight many of
      the advantages of these symbiont-based approaches and argue in favor of the
      broader recognition of crop species as ecological niches for a diverse community
      of microorganisms that function in concert with their plant hosts and each other
      to thrive under fluctuating environmental conditions. 

PMID- 24936205
TI  - Complex(iti)es of the ubiquitous RNA-binding CSP41 proteins.

PMID- 24936204
TI  - HvFT1 polymorphism and effect-survey of barley germplasm and expression analysis.
AB  - Flowering time in plants is a tightly regulated process. In barley (Hordeum
      vulgare L.), HvFT1, ortholog of FLOWERING LOCUS T, is the main integrator of the
      photoperiod and vernalization signals leading to the transition from vegetative
      to reproductive state of the plant. This gene presents sequence polymorphisms
      affecting flowering time in the first intron and in the promoter. Recently, copy
      number variation (CNV) has been described for this gene. An allele with more than
      one copy was linked to higher gene expression, earlier flowering, and an
      overriding effect of the vernalization mechanism. This study aims at (1)
      surveying the distribution of HvFT1 polymorphisms across barley germplasm and (2)
      assessing gene expression and phenotypic effects of HvFT1 alleles. We analyzed
      HvFT1 CNV in 109 winter, spring, and facultative barley lines. There was more
      than one copy of the gene (2-5) only in spring or facultative barleys without a
      functional vernalization VrnH2 allele. CNV was investigated in several regions
      inside and around HvFT1. Two models of the gene were found: one with the same
      number of promoters and transcribed regions, and another with one promoter and
      variable number of transcribed regions. This last model was found in Nordic
      barleys only. Analysis of HvFT1 expression showed that association between known
      polymorphisms at the HvFT1 locus and the expression of the gene was highly
      dependent on the genetic background. Under long day conditions the earliest
      flowering lines carried a sensitive PpdH1 allele. Among spring cultivars with
      different number of copies, no clear relation was found between CNV, gene
      expression and flowering time. This was confirmed in a set of doubled haploid
      lines of a population segregating for HvFT1 CNV. Earlier flowering in the
      presence of several copies of HvFT1 was only seen in cultivar Tammi, which
      carries one promoter, suggesting a relation of gene structure with its
      regulation. HvCEN also affected to a large extent flowering time. 

PMID- 24936203
TI  - CD8(+) T-Cell Responses in Acute Hepatitis C Virus Infection.
AB  - Hepatitis C virus (HCV) infects approximately 170 million people worldwide and is
      a major cause of life-threatening liver diseases such as liver cirrhosis and
      hepatocellular carcinoma. Acute HCV infection often progresses to chronic
      persistent infection, although some patients recover spontaneously. The divergent
      outcomes of acute HCV infection are known to be determined by differences in
      virus-specific T-cell responses among patients. Of the two major T-cell subsets,
      CD8(+) T-cells are known to be the key effector cells that control viral
      infections via cytolytic activity and cytokine secretion. Herein, we review
      various aspects of HCV-specific CD8(+) T-cell responses in acute HCV infection.
      In particular, we focus on timing of CD8(+) T-cell responses, relationship
      between CD8(+) T-cell responses and outcomes of acute HCV infection, receptor
      expression on CD8(+) T-cells, breadth of CD8(+) T-cell responses, and viral
      mutations. 

PMID- 24936206
TI  - Dichotomous branching: the plant form and integrity upon the apical meristem
      bifurcation.
AB  - The division of the apical meristem into two independently functioning axes is
      defined as dichotomous branching. This type of branching typically occurs in non
      vascular and non-seed vascular plants, whereas in seed plants it presents a
      primary growth form only in several taxa. Dichotomy is a complex process, which
      requires a re-organization of the meristem structure and causes changes in the
      apex geometry and activity. However, the mechanisms governing the repetitive apex
      divisions are hardly known. Here, an overview of dichotomous branching is
      presented, occurring in structurally different apices of phylogenetically distant
      plants, and in various organs (e.g., shoots, roots, rhizophores). Additionally,
      morphogenetic effects of dichotomy are reviewed, including its impact on
      organogenesis and mechanical constraints. At the end, the hormonal and genetic
      regulation of the dichotomous branching is discussed. 

PMID- 24936209
TI  - Enhancement of total sugar and lignin yields through dissolution of poplar wood
      by hot water and dilute acid flowthrough pretreatment.
AB  - BACKGROUND: Pretreatment is a vital but expensive step in biomass biofuel
      production. Overall, most of this past effort has been directed at maximizing
      sugar yields from hemicellulose and cellulose through trials with different
      chemicals, operating conditions, and equipment configurations. Flowthrough
      pretreatment provides a promising platform to dissolution of lignocellulosic
      biomass to generate high yields of fermentable sugars and lignin for biofuels
      productions. RESULTS: Dissolution of xylan, lignin, and cellulose from poplar
      wood were significantly enhanced by water-only and dilute acid (0.05% w/w, H2SO4)
      flowthrough pretreatment when the temperature was raised from 200 degrees C to
      280 degrees C over a range of flow rates 10-62.5 mL/min, resulting in more than
      98% solid removal. Up to 40% of original xylan was converted to xylose in the
      hydrolyzate and the rest xylan was solubilized into xylooligomers with negligible
      furfural formation. Up to 100% cellulose was removed into hydrolyzate with the
      highest glucose yield of 60% and low 5-hydroxymethylfurfural (5-HMF) formation.
      The maximal recovered insoluble lignin and soluble lignin were 98% and 15% of
      original lignin, respectively. In addition, enzymatic hydrolysis of pretreated
      whole slurries was characterized under various enzyme loadings with or without
      Bovine serum albumin (BSA) treatment. More than 90% glucose yield and 95% xylose
      yield were obtained from enzymatic hydrolysis of dilute acid pretreated whole
      slurries with 10 mg protein Ctec 2 with 2 mg Htec2/g glucan + xylan. CONCLUSIONS:
      Nearly complete dissolution of whole biomass was realized through water-only and
      dilute acid flowthrough pretreatment under tested conditions. Temperature was
      considered as the most significant factor for cellulose degradation. The
      cellulose removal significantly increased as temperature reached 240 degrees C
      for water-only and 220 degrees C for dilute acid. Dilute acid pretreatment
      resulted in higher yields of recovered xylan and cellulose as monomeric sugars in
      the hydrolyzate than that for water-only pretreatment. Enzymes readily hydrolyzed
      the degraded cellulose and xylooligomers in pretreatment hydrolysate. Results
      suggested that kinetics controlled the flowthrough pretreatment of biomass
      dissolution, which was also affected by flow rate to certain extent.

PMID- 24936208
TI  - Systematic analysis of human oncogenic viruses in colon cancer revealed EBV
      latency in lymphoid infiltrates.
AB  - BACKGROUND: Environmental factors may play a role in colon cancer. In this view,
      several studies investigated tumor samples for the presence of various viral DNA
      with conflicting results. FINDINGS: We undertook a systematic DNA analysis of 44
      consecutive, prospectively collected primary tumor samples by real time and
      qualitative PCR for viruses of known or potential oncogenic role in humans,
      including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and
      EBV. Negative controls consisted of surgical resection margins. No evidence of
      genomic DNA fragments from tested virus were detected, except for EBV, which was
      found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that
      EBV DNA was present at a highly variable content (median 258 copies in 10(5)
      cells, range 15-4837). Presence of EBV DNA had a trend to be associated with high
      lymphocyte infiltration (p = 0.06, chi2 test), and in situ hybridization with
      EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just
      a few scattered plasma cells positive for BZLF-1, an immediate early protein
      expressed during lytic replication. LMP-1 expression was undetectable by
      immunohistochemistry. CONCLUSIONS: These results argue against a significant
      involvement of the tested oncogenic viruses in established colon cancer.

PMID- 24936210
TI  - Reliable in vitro studies require appropriate ovarian cancer cell lines.
AB  - Ovarian cancer is the fifth most common cause of cancer death in women and the
      leading cause of death from gynaecological malignancies. Of the 75% women
      diagnosed with locally advanced or disseminated disease, only 30% will survive
      five years following treatment. This poor prognosis is due to the following
      reasons: limited understanding of the tumor origin, unclear initiating events and
      early developmental stages of ovarian cancer, lack of reliable ovarian cancer
      specific biomarkers, and drug resistance in advanced cases. In the past, in vitro
      studies using cell line models have been an invaluable tool for basic, discovery
      driven cancer research. However, numerous issues including misidentification and
      cross-contamination of cell lines have hindered research efforts. In this study
      we examined all ovarian cancer cell lines available from cell banks. Hereby, we
      identified inconsistencies in the reporting, difficulties in the identification
      of cell origin or clinical data of the donor patients, restricted ethnic and
      histological type representation, and a lack of tubal and peritoneal cancer cell
      lines. We recommend that all cell lines should be distributed via official cell
      banks only with strict guidelines regarding the minimal available information
      required to improve the quality of ovarian cancer research in future. 

PMID- 24936207
TI  - Long non-coding RNA-dependent transcriptional regulation in neuronal development
      and disease.
AB  - Comprehensive analysis of the mammalian transcriptome has revealed that long non
      coding RNAs (lncRNAs) may make up a large fraction of cellular transcripts.
      Recent years have seen a surge of studies aimed at functionally characterizing
      the role of lncRNAs in development and disease. In this review, we discuss new
      findings implicating lncRNAs in controlling development of the central nervous
      system (CNS). The evolution of the higher vertebrate brain has been accompanied
      by an increase in the levels and complexities of lncRNAs expressed within the
      developing nervous system. Although a limited number of CNS-expressed lncRNAs are
      now known to modulate the activity of proteins important for neuronal
      differentiation, the function of the vast majority of neuronal-expressed lncRNAs
      is still unknown. Topics of intense current interest include the mechanism by
      which CNS-expressed lncRNAs might function in epigenetic and transcriptional
      regulation during neuronal development, and how gain and loss of function of
      individual lncRNAs contribute to neurological diseases. 

PMID- 24936212
TI  - Robust features for the automatic identification of autism spectrum disorder in
      children.
AB  - BACKGROUND: It is commonly reported that children with autism spectrum disorder
      (ASD) exhibit hyper-reactivity or hypo-reactivity to sensory stimuli.
      Electroencephalography (EEG) is commonly used to study neural sensory reactivity,
      suggesting that statistical analysis of EEG recordings is a potential means of
      automatic classification of the disorder. EEG recordings taken from children,
      however, are frequently contaminated with large amounts of noise, making analysis
      difficult. In this paper, we present a method for the automatic extraction of
      noise-robust EEG features, which serve to quantify neural sensory reactivity. We
      show the efficacy of a system for the classification of ASD using these features.
      METHODS: An oddball paradigm was used to elicit event-related potentials from a
      group of 19 ASD children and 30 typically developing children. EEG recordings
      were taken and robust features were extracted. A support vector machine, logistic
      regression, and a naive Bayes classifier were used to classify the children as
      having ASD or being typically developing. RESULTS: A classification accuracy of
      79% was achieved, making our method competitive with other automatic diagnosis
      methods based on EEG. Additionally, we found that classification performance is
      reduced if eye blink artifacts are removed during preprocessing. CONCLUSIONS:
      This study shows that robust EEG features that quantify neural sensory reactivity
      are useful for the classification of ASD. We showed that noise-robust features
      are crucial for our analysis, and observe that traditional preprocessing methods
      may lead to poor classification performance in the face of a large amount of
      noise. Further exploration of alternative preprocessing methods is warranted.

PMID- 24936211
TI  - Experimental validation of FINDSITE(comb) virtual ligand screening results for
      eight proteins yields novel nanomolar and micromolar binders.
AB  - BACKGROUND: Identification of ligand-protein binding interactions is a critical
      step in drug discovery. Experimental screening of large chemical libraries, in
      spite of their specific role and importance in drug discovery, suffer from the
      disadvantages of being random, time-consuming and expensive. To accelerate the
      process, traditional structure- or ligand-based VLS approaches are combined with
      experimental high-throughput screening, HTS. Often a single protein or, at most,
      a protein family is considered. Large scale VLS benchmarking across diverse
      protein families is rarely done, and the reported success rate is very low. Here,
      we demonstrate the experimental HTS validation of a novel VLS approach,
      FINDSITE(comb), across a diverse set of medically-relevant proteins. RESULTS: For
      eight different proteins belonging to different fold-classes and from diverse
      organisms, the top 1% of FINDSITE(comb)'s VLS predictions were tested, and
      depending on the protein target, 4%-47% of the predicted ligands were shown to
      bind with MUM or better affinities. In total, 47 small molecule binders were
      identified. Low nanomolar (nM) binders for dihydrofolate reductase and protein
      tyrosine phosphatases (PTPs) and micromolar binders for the other proteins were
      identified. Six novel molecules had cytotoxic activity (<10 MUg/ml) against the
      HCT-116 colon carcinoma cell line and one novel molecule had potent antibacterial
      activity. CONCLUSIONS: We show that FINDSITE(comb) is a promising new VLS
      approach that can assist drug discovery.

PMID- 24936213
TI  - In vivo optical imaging of cancer metastasis using multiphoton microscopy: a
      short review.
AB  - Intravital (in vivo) microscopy using fluorescently-tagged proteins is a valuable
      tool for imaging the expression of a specific protein, its subcellular location
      and the dynamics of specific cell populations in living animals. Recently,
      multiphoton microscopy including two-photon laser scanning microscopy (TPLSM) has
      been used in the field of tumor biology due to its ability to image target organs
      at higher magnification and at deeper depths from the tissue surface for longer
      time periods. We developed a method of in vivo real-time imaging for tumor
      metastasis using TPLSM with an organ stabilizing system, which allow us to
      observe not only a single tumor cell and its microenvironment for a long time,
      but also to observe the same organ of the same mouse at multiple time points in
      preclinical models. Here, we presented in vivo real-time images of 1) tumor cell
      arrest, 2) tumor cell-platelet interaction, 3) tumor cell-leukocyte interaction,
      and 4) metastatic colonization at the secondary organs as representative steps of
      metastatic process of experimental liver metastasis models using TPLSM. 

PMID- 24936214
TI  - Small cell lung cancer cells express the late stage gBK tumor antigen: a possible
      immunotarget for the terminal disease.
AB  - Big Potassium (BK) ion channels have several splice variants. One splice variant
      initially described within human glioma cells is called the glioma BK channel
      (gBK). Using a gBK-specific antibody, we detected gBK within three human small
      cell lung cancer (SCLC) lines. Electrophysiology revealed that functional
      membrane channels were found on the SCLC cells. Prolonged exposure to BK channel
      activators caused the SCLC cells to swell within 20 minutes and resulted in their
      death within five hours. Transduction of BK-negative HEK cells with gBK produced
      functional gBK channels. Quantitative RT-PCR analysis using primers specific for
      gBK, but not with a lung-specific marker, Sox11, confirmed that advanced, late
      stage human SCLC tissues strongly expressed gBK mRNA. Normal human lung tissue
      and early, lower stage SCLC resected tissues very weakly expressed this
      transcript. Immunofluorescence using the anti-gBK antibody confirmed that SCLC
      cells taken at the time of the autopsy intensely displayed this protein. gBK may
      represent a late-stage marker for SCLC. HLA-A*0201 restricted human CTL were
      generated in vitro using gBK peptide pulsed dendritic cells. The exposure of SCLC
      cells to interferon-gamma (IFN-gamma) increased the expression of HLA; these
      treated cells were killed by the CTL better than non-IFN-gamma treated cells even
      though the IFN-gamma treated SCLC cells displayed diminished gBK protein
      expression. Prolonged incubation with recombinant IFN-gamma slowed the in vitro
      growth and prevented transmigration of the SCLC cells, suggesting IFN-gamma might
      inhibit tumor growth in vivo. Immunotherapy targeting gBK might impede
      advancement to the terminal stage of SCLC via two pathways. 

PMID- 24936215
TI  - HDAC inhibitors mitigate ischemia-induced oligodendrocyte damage: potential roles
      of oligodendrogenesis, VEGF, and anti-inflammation.
AB  - White matter injury is an important component of stroke pathology, but its
      pathophysiology and potential treatment remain relatively elusive and
      underexplored. We previously reported that after permanent middle cerebral artery
      occlusion (pMCAO), sodium butyrate (SB) and trichostatin A (TSA) induced
      neurogenesis via histone deacetylase (HDAC) inhibition in multiple ischemic brain
      regions in rats; these effects-which depended on activation of brain-derived
      neurotrophic factor (BDNF)-TrkB signaling-contributed to behavioral improvement.
      The present study found that SB or TSA robustly protected against ischemia
      induced loss of oligodendrocytes detected by confocal microscopy of myelin basic
      protein (MBP) immunostaining in the ipsilateral subventricular zone (SVZ),
      striatum, corpus callosum, and frontal cortex seven days post-pMCAO. Co
      localization of 5-bromo-2'-deoxyuridine (BrdU)(+) and MBP(+) cells after SB
      treatment suggested the occurrence of oligodendrogenesis. SB also strongly
      upregulated vascular endothelial growth factor (VEGF), which plays a major role
      in neurogenesis, angiogenesis, and functional recovery after stroke. These SB
      induced effects were markedly suppressed by blocking the TrkB signaling pathway
      with K252a. pMCAO-induced activation of microglia (OX42(+)) and
      macrophages/monocytes (ED1(+))-which has been linked to white matter injury-was
      robustly suppressed by SB in a K252a-sensitive manner. In addition, SB treatment
      largely blocked caspase-3(+) and OX42(+) cells in ipsilateral brain regions. Our
      results suggest that HDAC inhibitor-mediated protection against ischemia-induced
      oligodendrocyte loss may involve multiple mechanisms including
      oligodendrogenesis, VEGF upregulation, anti-inflammation, and caspase-3
      downregulation. Taken together, the results suggest that post-insult treatment
      with HDAC inhibitors is a rational strategy to mitigate white matter injury
      following ischemic stroke. 

PMID- 24936216
TI  - Transplantation of bone marrow stromal cells enhances infiltration and survival
      of CNP and Schwann cells to promote axonal sprouting following complete
      transection of spinal cord in adult rats.
AB  - This study aimed to investigate the roles of bone marrow stromal cells (BMSCs) in
      promoting axonal regeneration after complete transection of spinal cord in adult
      rats. Transplantation was done 9 days after injury. Only a few BMSCs were
      detected at the injury site 8 weeks after transplantation, yet there was robust
      growth of axons. The scarcity of surviving BMSCs may attribute to the adverse
      conditions in their ambient environment. In this connection, the immediate
      accumulation of a large number of macrophages/reactive microglia following BMSCs
      transplantation and subsequent cavitation of tissues may be detrimental to their
      survival. An unexpected finding following BMSCs transplantation was the marked
      increase in the nestin, GFAP, NF200, olig 3 and CNP positive cells at the injury
      site. Immunoelectron microscopy showed CNP cells were oval or fibroblast-like and
      had multiple perineurial-like compartments with long extending filopodia. The
      spatial relationship between regenerating axons and CNP-positive cells was also
      confirmed by double immunofluorescence staining. Our results suggest that
      transplantation of BMSCs elicits the influx and survival of local cells including
      CNP positive cells and Schwann cells into injury site, which provide structural
      support for the axon regeneration and remyelination after spinal cord injury. 

PMID- 24936217
TI  - Pro-growth role of the JMJD2C histone demethylase in HCT-116 colon cancer cells
      and identification of curcuminoids as JMJD2 inhibitors.
AB  - Colon tumors are a major cause of cancer death, yet their molecular intricacies
      are not fully understood. We demonstrate that the histone demethylases JMJD2A,
      JMJD2B and JMJD2C are overexpressed in colon cancer cell lines, whereas another
      related protein, JMJD2D, is not. Interestingly, despite their high homology, the
      intracellular localization of JMJD2A-C is different in colon and other cancer
      cells, with JMJD2A being present comparably in the cytoplasm and nucleus, JMJD2B
      more prevalent in the nucleus and JMJD2C strongly associated with chromatin. This
      suggests that each of these three proteins performs different, non-redundant
      functions. Moreover, we show that JMJD2C (also called KDM4C) forms complexes with
      beta-catenin, an oncoprotein whose overexpression is crucial for the development
      of most colonic tumors. In addition, JMJD2C downregulation reduced both growth
      and clonogenic capacity of HCT-116 colon cancer cells. Further, JMJD2C was
      required for efficient expression of the growth stimulatory proteins FRA1 and
      cyclin D1 as well as the survival factor BCL2. Lastly, we identified derivatives
      of curcumin as in vitro inhibitors of JMJD2 enzymes, suggesting that these
      curcuminoids could be useful for decreasing JMJD2 activity in vivo. In
      conclusion, our data highlight that overexpression of JMJD2C confers a pro-growth
      effect on colon cancer cells and, therefore, its inhibition by curcuminoids or
      other small molecules could be beneficial as an adjuvant therapy for colon cancer
      patients. 

PMID- 24936219
TI  - Comparative membrane proteomic analysis between lung adenocarcinoma and normal
      tissue by iTRAQ labeling mass spectrometry.
AB  - Lung adenocarcinoma, the most common type of lung cancer, has increased in recent
      years. Prognosis is still poor, and pathogenesis remains unclear. This study
      aimed to investigate the membrane protein profile differences between lung
      adenocarcinoma and normal tissue. Manual microdissection was used to isolate the
      target cells from tumor tissue and normal tissue. iTRAQ labeling combined with 2D
      LC-MS/MS yielded a differential expression profile of membrane proteins.
      Bioinformatic analysis was performed using Gene Ontology, WEGO, PID, and KEGG.
      S100A14 protein was selectively verified by Western blotting. The relationship of
      S100A14 expression with clinicopathological features in lung cancer patients was
      evaluated using immunohistochemistry. As a result, 568 differential proteins were
      identified; 257 proteins were upregulated and 311 were downregulated. Of these
      proteins, 48% were found to be membrane bound or membrane associated. These
      proteins enable the physiological functions of binding, catalysis, molecular
      transduction, transport, and molecular structure. For these differential
      proteins, 35 pathways were significantly enriched through the Pathway Interaction
      Database, whereas 19 pathways were enriched via KEGG. The overexpression and
      cellular distribution of S100A14 in lung cancer were confirmed. We found that
      upregulation of S100A14 was associated with well or moderate differentiation. The
      iTRAQ-coupled 2D-LC-MS/MS technique is a potential method for comparing membrane
      protein profiles between tumor and normal tissue. Such analysis may also help in
      identifying novel biomarkers and the mechanisms underlying carcinogenesis. 

PMID- 24936218
TI  - Mouse mammary tumor virus-like virus infection and the risk of human breast
      cancer: a meta-analysis.
AB  - Despite a large number of molecular epidemiological studies, the association of
      Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) infection with the risk of human
      breast cancer remains inconclusive mainly due to the heterogeneity in populations
      involved. We performed a systematic search of multiple bibliographic databases,
      up to October 2013, to identify all studies on detection of MMTV-LV DNA in human
      breast cancer using polymerase chain reaction (PCR) and conducted the first
      comprehensive meta-analysis of published literature to explore the relevance of
      MMTV-LV to human breast cancer. As a result, meta-analysis of twelve case-control
      studies identified from the systematic search revealed a significantly increased
      risk for breast cancer development after MMTV-LV infection (OR=15.20; 95% CI:
      9.98-23.13). However, there was no significant correlation between MMTV-LV
      infection and the transformation from ductal carcinoma in situ to invasive ductal
      carcinoma (OR=1.16; 95% CI: 0.27-4.97). In addition, MMTV-LV infection was not
      associated with the expression of estrogen receptor (ER) (OR=0.89; 95% CI: 0.48
      1.65), progesterone receptor (PR) (OR=0.73; 95% CI: 0.22-2.42), HER-2 (OR=0.65;
      95% CI: 0.30-1.43) or p53 (OR=1.47; 95% CI: 0.79-2.73). Finally, we found that
      the prevalence of MMTV-LV in breast carcinoma was significantly higher in
      patients from Western countries (prevalence=40.4%, 95% CI: 28.9%-51.9%) than in
      Asian patients (prevalence: 8.5%; 95% CI: -7.1%-24.1%) in a subgroup and meta
      regression analysis (p=0.015). In summary, the meta-analysis of published studies
      revealed a significantly increased risk for breast cancer development after MMTV
      LV infection. In addition, the prevalence of MMTV-LV is much higher in breast
      cancer patients from Western countries than Asian patients. 

PMID- 24936220
TI  - Pulsed electromagnetic field improves cardiac function in response to myocardial
      infarction.
AB  - Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to
      improve regeneration in various ischemic episodes. Here, we examined whether PEMF
      therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the
      cellular/molecular mechanisms underlying PEMF-related therapy was further
      investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8
      minutes/cycle, 30 +/- 3 Hz, 5 mT) after MI induction. The data demonstrated that
      PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac
      systolic function. Moreover, PEMF treatment increased capillary density, the
      levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor
      1alpha in infarct border zone. Furthermore, the number and function of
      circulating endothelial progenitor cells were advanced in PEMF treating rats. In
      vitro, PEMF induced the degree of human umbilical venous endothelial cells
      tubulization and increased soluble pro-angiogenic factor secretion (VEGF and
      nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function,
      inhibits apoptosis and trigger postnatal neovascularization in ischemic
      myocardium. 

PMID- 24936221
TI  - Engineered 3D bioimplants using elastomeric scaffold, self-assembling peptide
      hydrogel, and adipose tissue-derived progenitor cells for cardiac regeneration.
AB  - Contractile restoration of myocardial scars remains a challenge with important
      clinical implications. Here, a combination of porous elastomeric membrane,
      peptide hydrogel, and subcutaneous adipose tissue-derived progenitor cells
      (subATDPCs) was designed and evaluated as a bioimplant for cardiac regeneration
      in a mouse model of myocardial infarction. SubATDPCs were doubly transduced with
      lentiviral vectors to express bioluminescent-fluorescent reporters driven by
      constitutively active, cardiac tissue-specific promoters. Cells were seeded into
      an engineered bioimplant consisting of a scaffold (polycaprolactone
      methacryloyloxyethyl ester) filled with a peptide hydrogel (PuraMatrixTM), and
      transplanted to cover injured myocardium. Bioluminescence and fluorescence
      quantifications showed de novo and progressive increases in promoter expression
      in bioactive implant-treated animals. The bioactive implant was well adapted to
      the heart, and fully functional vessels traversed the myocardium-bioactive
      implant interface. Treatment translated into a detectable positive effect on
      cardiac function, as revealed by echocardiography. Thus, this novel implant is a
      promising construct for supporting myocardial regeneration. 

PMID- 24936222
TI  - Pathway-based analysis of breast cancer.
AB  - INTRODUCTION: Although HER2 and ER pathways are predominant pathways altered in
      breast cancer, it is now well accepted that many other signaling pathways are
      also involved in the pathogenesis of breast cancer. The understanding of these
      additional pathways may assist in identifying new therapeutic approaches for
      breast cancer. METHODS: 13 invasive ductal carcinoma tissues and 5 benign breast
      tissues were analyzed for the mRNA expression level of 1243 cancer pathway
      related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In
      addition, the levels of 131 cancer pathway-related proteins and phosphoproteins
      in 33 paired breast cancers were measured using our innovative Protein Pathway
      Array. RESULTS: Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer
      and 395 mRNAs were statistically significant (fold change >2) between benign and
      cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and
      33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and
      phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were
      significantly differentiated between tumor and normal tissues. Interestingly,
      only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA.
      Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially
      expressed between tumor and normal tissues but no differences were observed at
      mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis
      showed more than 15 pathways were altered in breast cancer and 6 of which were
      shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and
      PI3K/AKT pathways. CONCLUSIONS: There is a broad dysregulation of various
      pathways in breast cancer both at protein levels and mRNA levels. It is important
      to note that mRNA expression does not correlate with protein level, suggesting
      different regulation mechanisms between proteins and mRNAs.

PMID- 24936223
TI  - IFN-beta alters neurotrophic factor expression in T cells isolated from multiple
      sclerosis patients - implication of novel neurotensin/NTSR1 pathway in
      neuroprotection.
AB  - Inflammation in relapsing remitting multiple sclerosis (RRMS) is hypothesized to
      provide neuroprotective effects via altered cytokine/neurotrophin homeostasis.
      The distinct neurotrophin production from specific cell populations has not been
      systematically studied and is likely of high yield in understanding the complex
      regulation of MS pathogenesis. Here, we describe how the mainstream therapy
      interferon-beta (IFN-beta) modulates neurotrophin expression in T cells isolated
      from RRMS patients and characterize the neuroprotective capabilities of these
      factors. We utilize SuperArray gene screen technology to investigate the
      neurotrophin expression profile of T cells. We demonstrate that IFN-beta induces
      an anti-inflammatory cytokine expression pattern in T cells. Additionally, IFN
      beta upregulates the expression of a novel neurotrophin receptor, the neurotensin
      high affinity receptor 1 (NTSR1). NTSR1 is expressed in active demyelinating
      lesions. Furthermore, we demonstrate that the receptor agonist neurotensin is a
      potent inducer of human neural stem/progenitor cell survival. Our findings
      highlight the importance of neurotrophin receptors in RRMS and offer insight into
      disease pathogenesis as well as the mechanisms of action of IFN-beta. 

PMID- 24936224
TI  - Baroreflex deficiency induces additional impairment of vagal tone, diastolic
      function and calcium handling proteins after myocardial infarction.
AB  - Baroreflex dysfunction has been considered an important mortality predictor after
      myocardial infarction (MI). However, the impact of baroreflex deficiency prior to
      MI on tonic autonomic control and cardiac function, and on the profile of
      proteins associated with intracellular calcium handling has not yet been studied.
      The aim of the present study was to analyze how the impairment of baroreflex
      induced by sinoaortic denervation (SAD) prior to MI in rats affects the tonic
      autonomic control, ventricular function and cardiomyocyte calcium handling
      proteins. After 15 days of following or SAD surgery, rats underwent MI.
      Echocardiographic, hemodynamic, autonomic and molecular evaluations were
      performed 90 days after MI. Baroreflex impairment led to additional damage on:
      left ventricular remodeling, diastolic function, vagal tonus and intrinsic heart
      rate after MI. The loss of vagal component of the arterial baroreflex and vagal
      tonus were correlated with changes in the cardiac proteins involved in
      intracellular calcium homeostasis. Furthermore, additional increase in sodium
      calcium exchanger expression levels was associated with impaired diastolic
      function in experimental animals. Our findings strongly suggest that previous
      arterial baroreflex deficiency may induce additional impairment of vagal tonus,
      which was associated with calcium handling proteins abnormalities, probably
      triggering ventricular diastolic dysfunction after MI in rats. 

PMID- 24936225
TI  - Operable gastro-oesophageal junctional adenocarcinoma: Where to next?
AB  - Oesophageal junctional adenocarcinoma is a challenging and increasingly common
      disease. Optimisation of pre-operative staging and consolidation of surgery in
      large volume centres have improved outcomes, however the preferred adjunctive
      treatment approach remains a matter of debate. This review examines the benefits
      of neoadjuvant, peri-operative, and post-operative chemotherapy and
      chemoradiotherapy in this setting in an attempt to reach an evidence based
      conclusion. Recent findings relating to the molecular characterisation of
      oesophagogastric cancer and their impact on therapeutics are explored, in
      addition to the potential benefits of fluoro-deoxyglucose positron emission
      tomography (FDG-PET) directed therapy. Finally, efforts to decrease the incidence
      of junctional adenocarcinoma using early intervention in Barrett's oesophagus are
      discussed, including the roles of screening, endoscopic mucosal resection,
      ablative therapies and chemoprevention. 

PMID- 24936226
TI  - Primary tumor resection in colorectal cancer with unresectable synchronous
      metastases: A review.
AB  - At the time of diagnosis, 25% of patients with colorectal cancer (CRC) present
      with synchronous metastases, which are unresectable in the majority of patients.
      Whether primary tumor resection (PTR) followed by chemotherapy or immediate
      chemotherapy without PTR is the best therapeutic option in patients with
      asymptomatic CRC and unresectable metastases is a major issue, although
      unanswered to date. The aim of this study was to review all published data on
      whether PTR should be performed in patients with CRC and unresectable synchronous
      metastases. All aspects of the management of CRC were taken into account,
      especially prognostic factors in patients with CRC and unresectable metastases.
      The impact of PTR on survival and quality of life were reviewed, in addition to
      the characteristics of patients that could benefit from PTR and the possible
      underlying mechanisms. The risks of both approaches are reported. As no
      randomized study has been performed to date, we finally discussed how a
      therapeutic strategy's trial should be designed to provide answer to this issue. 

PMID- 24936227
TI  - Monoclonal antibodies that target the immunogenic proteins expressed in
      colorectal cancer.
AB  - In an attempt to improve upon the end results obtained in treating colorectal
      cancer it was apparent that the earlier the diagnosis that could be obtained, the
      better the chance for obtaining desired results. In the case of more advanced
      tumors typified by later stage colorectal cancer, surgical debulking is an
      important part of the treatment strategy. Here the use of additional therapeutic
      modalities including chemotherapy and present day immunotherapy has failed to
      accomplish the desired improvements that have been sought after. Adjuvant
      therapy, has offered little to the overall survival. The concept of early
      detection is now recognized as the initial step in reaching proper end results
      and can readily be demonstrated from colorectal cancer studies. Here survival has
      been found to be a reflection of the stage at which the tumor is first identified
      and treated. When specific monoclonals targeting colorectal cancer are employed
      diagnostically, we have been able to demonstrate detection of colorectal cancer
      at its inception as a premalignant lesion, such that genotypic features can be
      identified before the phenotypic appearance of cancer can be noted. 

PMID- 24936228
TI  - Current status of pharmacological treatment of colorectal cancer.
AB  - AIM: To review the clinical trials for the development in drugs for
      chemotherapeutic treatment of colorectal cancer (CRC). METHODS: A systematic
      review identified randomized controlled trials (RCTs) assessing drugs for the
      treatment of CRC or adenomatous polyps from www.clinicaltrials.gov. Various
      online medical databases were searched for relevant publications. RESULTS:
      Combination treatment regimens of standard drugs with newer agents have been
      shown to improve overall survival, disease-free survival, time to progression and
      quality of life compared to that with standard drugs alone in patients with
      advanced colorectal cancer. The FOLFOXIRI regimen has been associated with a
      significantly higher response rate, progression-free survival and overall
      survival compared to the FOLFIRI regimen. CONCLUSION: Oxaliplatin plus
      intravenous bolus fluorouracil and leucovorin has been shown to be superior for
      disease-free survival when compared to intravenous bolus fluorouracil and
      leucovorin. In addition, oxaliplatin regimens were more likely to result in
      successful surgical resections. First line treatment with cetuximab plus
      fluorouracil, leucovorin and irinotecan has been found to reduce the risk of
      metastatic progression in patients with epidermal growth factor receptor-positive
      colorectal cancer with unresectable metastases. The addition of bevacizumab has
      been shown to significantly increase overall and progression-free survival when
      given in combination with standard therapy.

PMID- 24936229
TI  - Robotic surgery for rectal cancer: A systematic review of current practice.
AB  - AIM: To give a comprehensive review of current literature on robotic rectal
      cancer surgery. METHODS: A systematic review of current literature via PubMed and
      Embase search engines was performed to identify relevant articles from january
      2007 to november 2013. The keywords used were: "robotic surgery", "surgical
      robotics", "laparoscopic computer-assisted surgery", "colectomy" and "rectal
      resection". RESULTS: After the initial screen of 380 articles, 20 papers were
      selected for review. A total of 1062 patients (male 64.0%) with a mean age of
      61.1 years and body mass index of 24.9 kg/m(2) were included in the review. Out
      of 1062 robotic-assisted operations, 831 (78.2%) anterior and low anterior
      resections, 132 (12.4%) intersphincteric resection with coloanal anastomosis, 98
      (9.3%) abdominoperineal resections and 1 (0.1%) Hartmann's operation were
      included in the review. Robotic rectal surgery was associated with longer
      operative time but with comparable oncological results and anastomotic leak rate
      when compared with laparoscopic rectal surgery. CONCLUSION: Robotic colorectal
      surgery has continued to evolve to its current state with promising results;
      feasible surgical option with low conversion rate and comparable short-term
      oncological results. The challenges faced with robotic surgery are for more high
      quality studies to justify its cost.

PMID- 24936230
TI  - SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism.
AB  - SMARTCyp is an in silico method that predicts the sites of cytochrome P450
      mediated metabolism of druglike molecules. The method is foremost a reactivity
      model, and as such, it shows a preference for predicting sites that are
      metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of
      metabolism directly from the 2D structure of a molecule, without requiring
      calculation of electronic properties or generation of 3D structures. This is a
      major advantage, because it makes SMARTCyp very fast. Other advantages are that
      experimental data are not a prerequisite to create the model, and it can easily
      be integrated with other methods to create models for other cytochrome P450
      isoforms. Benchmarking tests on a database of 394 3A4 substrates show that
      SMARTCyp successfully identifies at least one metabolic site in the top two
      ranked positions 76% of the time. SMARTCyp is available for download at
      http://www.farma.ku.dk/p450. 

PMID- 24936232
TI  - Discovery of Potent Dual PPARalpha Agonists/CB1 Ligands.
AB  - This letter describes the synthesis and in vitro and in vivo evaluation of dual
      ligands targeting the cannabinoid and peroxisome proliferator-activated receptors
      (PPAR). These compounds were obtained from fusing the pharmacophores of fibrates
      and the diarylpyrazole rimonabant, a cannabinoid receptor antagonist. They are
      the first examples of dual compounds with nanomolar affinity for both PPARalpha
      and cannabinoid receptors. Besides, lead compound 2 proved to be CB1 selective.
      Unexpectedly, the phenol intermediates tested were equipotent (compound 1 as
      compared to 2) or even more potent (compound 3 as compared with 4). This
      discovery opens the way to design new dual ligands. 

PMID- 24936231
TI  - A kappa Opioid Pharmacophore Becomes a Spinally Selective kappa-delta Agonist
      When Modified with a Basic Extender Arm.
AB  - We have explored the concept of a molecular extender arm attached to a kappa
      opioid agonist pharmacophore 3 (ICI-199,441) in an effort to potentially interact
      with a complementary group on a neighboring opioid receptor. The molecular arm
      containing a terminal amine group was lengthened incrementally from 11 up to 18
      atoms. Increasing the number of atoms in the arm produced virtually no change in
      the mouse intracerebroventricular (i.c.v.) antinociceptive potency. In contrast,
      the intrathecal (i.t.) potency of 6 (KDA-16) with a 16-atom arm was dramatically
      increased, as reflected by its antinociceptive i.c.v./i.t. ED50 ratio of ~130.
      Further lengthening led to a decreased ED50 ratio. In vivo selective antagonist
      studies of KDA-16 revealed that kappa and delta opioid receptors were responsible
      for the greatly enhanced i.t. potency. Calcium release experiments in HEK-293
      cells suggested that KDA-16 selectively activate kappa-delta heteromers. These
      data are consistent with the reported possible presence of heteromeric kappa
      delta opioid receptors in mouse spinal cord but not in the brain. The use of a
      molecular extender arm may be useful for developing spinally selective
      analgesics. 

PMID- 24936233
TI  - Discovery of Novel alpha4beta2 Neuronal Nicotinic Receptor Modulators through
      Structure-Based Virtual Screening.
AB  - We performed a hierarchical structure-based virtual screening utilizing a
      comparative model of the human alpha4beta2 neuronal nicotinic acetylcholine
      receptor (nAChR) extracellular domain. Compounds were selected for experimental
      testing based on structural diversity, binding pocket location, and standard
      error of the free energy scoring function used in the screening. Four of the
      eleven in silico hit compounds showed promising activity with low micromolar IC50
      values in a calcium accumulation assay. Two of the antagonists were also proven
      to be selective for human alpha4beta2 vs human alpha3beta4 nAChRs. This is the
      first report of successful discovery of novel nAChR antagonists through the use
      of structure-based virtual screening with a human nAChR homology model. These
      compounds may serve as potential novel scaffolds for further development of
      selective nAChR antagonists. 

PMID- 24936235
TI  - 1,4-naphthoquinone cations as antiplasmodial agents: hydroxy-, acyloxy-, and
      alkoxy-substituted analogues.
AB  - Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated
      as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues
      were found to be inactive as antagonists of parasite growth, which was attributed
      to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy
      substituent, the antiplasmodial activity was restored in the sub-100 nM range.
      Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against
      heteroresistant P. falciparum W2. 

PMID- 24936234
TI  - Synthesis and biological evaluation of a selective N- and p/q-type calcium
      channel agonist.
AB  - The acute effect of the potent cyclin-dependent kinase (cdk) inhibitor (R)
      roscovitine on Ca(2+) channels inspired the development of structural analogues
      as a potential treatment for motor nerve terminal dysfunction. On the basis of a
      versatile chlorinated purine scaffold, we have synthesized ca. 20 derivatives and
      characterized their N-type Ca(2+) channel agonist action. Agents that showed
      strong agonist effects were also characterized in a kinase panel for their off
      target effects. Among several novel compounds with diminished cdk activity, we
      identified a new lead structure with a 4-fold improved N-type Ca(2+) channel
      agonist effect and a 22-fold decreased cdk2 activity as compared to (R)
      roscovitine. This compound was selective for agonist activity on N- and P/Q-type
      over L-type calcium channels. 

PMID- 24936236
TI  - Molecular Docking and in Vitro Antileishmanial Evaluation of Chromene-2-thione
      Analogues.
AB  - Leishmaniases are an epidemic in various countries, and the parasite is
      developing resistance against available drugs. Thus, development of new drugs
      against Leishmania is an open area of investigation for synthetic organic
      chemists. To meet this challenge, a series of chromene-2-thione derivatives have
      been synthesized and docked into the active site of trypanothione reductase
      (TryR) enzyme required for redox balance of the parasite. These were screened on
      promastigote, axenic amastigote, and intracellular amastigote stages of
      Leishmania donovani and found to show high levels of antileishmanial activity
      together with minimal toxicity to human peripheral blood mononuclear cells.
      Compounds 3b and 3k were found to be the most active among the tested compounds.
      Although the compounds show moderate antileishmanial activity, they identify a
      chemical space to design and develop drugs based on these chromene-2-thione
      derivatives against the Leishmania parasite. 

PMID- 24936237
TI  - The beta-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is Believing.

PMID- 24936239
TI  - Fluorescent carbon nanoparticles in medicine for cancer therapy.
AB  - Nanotechnology provides exciting opportunities for the development of novel,
      clinically relevant diagnostic and therapeutic multifunctional systems.
      Fluorescent carbon nanoparticles (CNPs) due to their intrinsic fluorescence and
      high biocompatibility are among the best candidates. As innovative nanomaterials,
      CNPs could be utilized both as nontoxic drug delivery system and bioimaging. We
      foresee a great future for CNPs in cancer diagnostic and therapy. 

PMID- 24936238
TI  - Binding Model for the Interaction of Anticancer Arylsulfonamides with the p300
      Transcription Cofactor.
AB  - Hypoxia inducible factors (HIFs) are transcription factors that activate
      expression of multiple gene products and promote tumor adaptation to a hypoxic
      environment. To become transcriptionally active, HIFs associate with cofactors
      p300 or CBP. Previously, we found that arylsulfonamides can antagonize HIF
      transcription in a bioassay, block the p300/HIF-1alpha interaction, and exert
      potent anticancer activity in several animal models. In the present work, KCN1
      bead affinity pull down, (14)C-labeled KCN1 binding, and KCN1-surface plasmon
      resonance measurements provide initial support for a mechanism in which KCN1 can
      bind to the CH1 domain of p300 and likely prevent the p300/HIF-1alpha assembly.
      Using a previously reported NMR structure of the p300/HIF-1alpha complex, we have
      identified potential binding sites in the p300-CH1 domain. A two-site binding
      model coupled with IC50 values has allowed establishment of a modest ROC-based
      enrichment and creation of a guide for future analogue synthesis. 

PMID- 24936240
TI  - Discovery of tetrahydroisoquinoline-based CXCR4 antagonists.
AB  - A de novo hit-to-lead effort involving the redesign of benzimidazole-containing
      antagonists of the CXCR4 receptor resulted in the discovery of a novel series of
      1,2,3,4-tetrahydroisoquinoline (TIQ) analogues. In general, this series of
      compounds show good potencies (3-650 nM) in assays involving CXCR4 function,
      including both inhibition of attachment of X4 HIV-1IIIB virus in MAGI-CCR5/CXCR4
      cells and inhibition of calcium release in Chem-1 cells. Series profiling
      permitted the identification of TIQ-(R)-stereoisomer 15 as a potent and selective
      CXCR4 antagonist lead candidate with a promising in vitro profile. The drug-like
      properties of 15 were determined in ADME in vitro studies, revealing low
      metabolic liability potential. Further in vivo evaluations included
      pharmacokinetic experiments in rats and mice, where 15 was shown to have oral
      bioavailability (F = 63%) and resulted in the mobilization of white blood cells
      (WBCs) in a dose-dependent manner. 

PMID- 24936241
TI  - Pharmaceutical profiling case study in disruption.

PMID- 24936242
TI  - 3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease.
AB  - Several 3-hydroxyquinolin-2(1H)-ones derivatives were synthesized and evaluated
      as inhibitors of 2009 pandemic H1N1 influenza A endonuclease. All five of the
      monobrominated 3-hydroxyquinolin(1H)-2-ones derivatives were synthesized. Suzuki
      coupling of p-fluorophenylboronic acid with each of these brominated derivatives
      provided the respective p-fluorophenyl 3-hydroxyquinolin(1H)-2-ones. In addition
      to 3-hydroxyquinolin-2(1H)-one, its 4-methyl, 4-phenyl, 4-methyl-7-(p
      fluorophenyl), and 4-phenyl-7-(p-fluorophenyl) derivatives were also synthesized.
      Comparative studies on their relative activity revealed that both 6- and 7-(p
      fluorophenyl)-3-hydroxyquinolin-2(1H)-one are among the more potent inhibitors of
      H1N1 influenza A endonuclease. An X-ray crystal structure of 7-(p-fluorophenyl)-3
      hydroxyquinolin-2(1H)-one complexed to the influenza endonuclease revealed that
      this molecule chelates to two metal ions at the active site of the enzyme. 

PMID- 24936243
TI  - Expedient Synthesis of SMAMPs via Click Chemistry.
AB  - A novel series of synthetic mimics of antimicrobial peptides (SMAMPs) containing
      triazole linkers were assembled using click chemistry. While only moderately
      active in buffer alone, an increase in antimicrobial activity against
      Staphylococcus aureus and Escherichia coli was observed when these SMAMPs were
      administered in the presence of mouse serum. One compound had minimum inhibitory
      concentrations (MICs) of 0.39 MUg/mL and 6.25 MUg/mL, respectively, and an HC50
      of 693 MUg/mL. These values compared favorably to peptide-based antimicrobials. A
      correlation between the net positive charge and SMAMP antimicrobial activity was
      observed. The triazole linker, an amide surrogate, was found to provide better
      antimicrobial activity against both S. aureus and E. coli when compared to other
      analogues. 

PMID- 24936244
TI  - Short acting insulin analogues in intensive care unit patients.
AB  - BLOOD GLUCOSE CONTROL IN INTENSIVE CARE UNIT (ICU) PATIENTS, ADDRESSED TO
      ACTIVELY MAINTAIN BLOOD GLUCOSE CONCENTRATION WITHIN DEFINED THRESHOLDS, IS BASED
      ON TWO MAJOR THERAPEUTIC INTERVENTIONS: to supply an adequate calories load and,
      when necessary, to continuously infuse insulin titrated to patients needs:
      intensive insulin therapy (IIT). Short acting insulin analogues (SAIA) have been
      synthesized to improve the chronic treatment of patients with diabetes but,
      because of the pharmacokinetic characteristics that include shorter on-set and
      off-set, they can be effectively used also in ICU patients and have the potential
      to be associated with a more limited risk of inducing episodes of iatrogenic
      hypoglycemia. Medical therapies carry an intrinsic risk for collateral effects;
      this can be more harmful in patients with unstable clinical conditions like ICU
      patients. To minimize these risks, the use of short acting drugs in ICU patients
      have gained a progressively larger room in ICU and now pharmaceutical companies
      and researchers design drugs dedicated to this subset of medical practice. In
      this article we report the rationale of using short acting drugs in ICU patients
      (i.e., sedation and treatment of arterial hypertension) and we also describe SAIA
      and their therapeutic use in ICU with the potential to minimize iatrogenic
      hypoglycemia related to IIT. The pharmacodynamic and pharmachokinetic
      characteristics of SAIA will be also discussed. 

PMID- 24936245
TI  - Adipose stem cell-based regenerative medicine for reversal of diabetic
      hyperglycemia.
AB  - Diabetes mellitus (diabetes) is a devastating disease that affects millions of
      people globally and causes a myriad of complications that lead to both patient
      morbidity and mortality. Currently available therapies, including insulin
      injection and beta cell replacement through either pancreas or pancreatic islet
      transplantation, are limited by the availability of organs. Stem cells provide an
      alternative treatment option for beta cell replacement through selective
      differentiation of stem cells into cells that recognize glucose and produce and
      secrete insulin. Embryonic stem cells, albeit pluripotent, face a number of
      challenges, including ethical and political concerns and potential teratoma
      formation. Adipose tissue represents an alternative source of multipotent
      mesenchymal stem cells, which can be obtained using a relatively simple, non
      invasive, and inexpensive method. Similarly to other adult mesenchymal stem
      cells, adipose-derived stem cells (ADSCs) are capable of differentiating into
      insulin-producing cells. They are also capable of vasculogenesis and
      angiogenesis, which facilitate engraftment of donor pancreatic islets when co
      transplanted. Additionally, anti-inflammatory and immunomodulatory effects of
      ADSCs can protect donor islets during the early phase of transplantation and
      subsequently improve engraftment of donor islets into the recipient organ.
      Although ADSC-therapy is still in its infancy, the potential benefits of ADSCs
      are far reaching. 

PMID- 24936246
TI  - Defect of insulin signal in peripheral tissues: Important role of ceramide.
AB  - In healthy people, balance between glucose production and its utilization is
      precisely controlled. When circulating glucose reaches a critical threshold
      level, pancreatic beta cells secrete insulin that has two major actions: to lower
      circulating glucose levels by facilitating its uptake mainly into skeletal muscle
      while inhibiting its production by the liver. Interestingly, dietary
      triglycerides are the main source of fatty acids to fulfill energy needs of
      oxidative tissues. Normally, the unconsumed fraction of excess of fatty acids is
      stored in lipid droplets that are localized in adipocytes to provide energy
      during fasting periods. Thus, adipose tissue acts as a trap for fatty acid excess
      liberated from plasma triglycerides. When the buffering action of adipose tissue
      to store fatty acids is impaired, fatty acids that build up in other tissues are
      metabolized as sphingolipid derivatives such as ceramides. Several studies
      suggest that ceramides are among the most active lipid second messengers to
      inhibit the insulin signaling pathway and this review describes the major role
      played by ceramide accumulation in the development of insulin resistance of
      peripherals tissues through the targeting of specific proteins of the insulin
      signaling pathway. 

PMID- 24936247
TI  - Impact of hypoglycemic agents on myocardial ischemic preconditioning.
AB  - Murry et al in 1986 discovered the intrinsic mechanism of profound protection
      called ischemic preconditioning. The complex cellular signaling cascades
      underlying this phenomenon remain controversial and are only partially
      understood. However, evidence suggests that adenosine, released during the
      initial ischemic insult, activates a variety of G protein-coupled agonists, such
      as opioids, bradykinin, and catecholamines, resulting in the activation of
      protein kinases, especially protein kinase C (PKC). This leads to the
      translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates
      the opening of the ATP-sensitive K(+) channel, which confers resistance to
      ischemia. It is known that a range of different hypoglycemic agents that activate
      the same signaling cascades at various cellular levels can interfere with
      protection from ischemic preconditioning. This review examines the effects of
      several hypoglycemic agents on myocardial ischemic preconditioning in animal
      studies and clinical trials. 

PMID- 24936249
TI  - Why do some patients with type 1 diabetes live so long?
AB  - While the lifespan of people with type 1 diabetes has increased progressively
      since the advent of insulin therapy, these patients still experience premature
      mortality, primarily from cardiovascular disease (CVD). However, a subgroup of
      those with type 1 diabetes survives well into old age without significant
      morbidity. It is the purpose of this review to explore the factors which may help
      in identifying these patients. It might be expected that hyperglycaemia plays a
      major role in explaining the increased incidence of CVD and mortality of these
      individuals. However, while a number of publications have associated poor long
      term glycaemic control with an increase in both all-cause mortality and CVD in
      those with type 1 diabetes, it is apparent that good glycaemic control alone
      cannot explain why some patients with type 1 diabetes avoid fatal CVD events.
      Lipid disorders may occur in those with type 1 diabetes, but the occurrence of
      elevated high-density lipoprotein-cholesterol is positively associated with
      longevity in this population. Non-renal hypertension, by itself is a significant
      risk factor for CVD but if adequately treated does not appear to mitigate against
      longevity. However, the presence of nephropathy is a major risk factor and its
      absence after 15-20 years of diabetes appears to be a marker of long-term
      survival. One of the major factors linked with long-term survival is the absence
      of features of the metabolic syndrome and more specifically the presence of
      insulin sensitivity. Genetic factors also play a role, with a family history of
      longevity and an absence of type 2 diabetes and hypertension in the family being
      important considerations. There is thus a complex interaction between multiple
      risk factors in determining which patients with type 1 diabetes are likely to
      live into older age. However, these patients can often be identified clinically
      based on a combination of factors as outlined above. 

PMID- 24936250
TI  - Evidence for altered thiamine metabolism in diabetes: Is there a potential to
      oppose gluco- and lipotoxicity by rational supplementation?
AB  - Growing prevalence of diabetes (type 2 as well as type 1) and its related
      morbidity due to vascular complications creates a large burden on medical care
      worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and
      avascular complications mediated by hyperglycemia is of crucial importance since
      novel therapeutic targets can be identified and tested. Thiamine (vitamin B1) is
      an essential cofactor of several enzymes involved in carbohydrate metabolism and
      published data suggest that thiamine metabolism in diabetes is deficient. This
      review aims to point out the physiological role of thiamine in metabolism of
      glucose and amino acids, to present overview of thiamine metabolism and to
      describe the consequences of thiamine deficiency (either clinically manifest or
      latent). Furthermore, we want to explain why thiamine demands are increased in
      diabetes and to summarise data indicating thiamine mishandling in diabetics (by
      review of the studies mapping the prevalence and the degree of thiamine
      deficiency in diabetics). Finally, we would like to summarise the evidence for
      the beneficial effect of thiamine supplementation in progression of hyperglycemia
      related pathology and, therefore, to justify its importance in determining the
      harmful impact of hyperglycemia in diabetes. Based on the data presented it could
      be concluded that although experimental studies mostly resulted in beneficial
      effects, clinical studies of appropriate size and duration focusing on the effect
      of thiamine supplementation/therapy on hard endpoints are missing at present.
      Moreover, it is not currently clear which mechanisms contribute to the deficient
      action of thiamine in diabetes most. Experimental studies on the molecular
      mechanisms of thiamine deficiency in diabetes are critically needed before clear
      answer to diabetes community could be given. 

PMID- 24936251
TI  - Social determinants of type 2 diabetes and health in the United States.
AB  - Diabetes is the sixth leading cause of death in the United States. To date, most
      research and resulting clinical strategies have focused on the individual with
      short-term health improvements that have not been maintained over time.
      Researchers more recently have recognized the need to consider the social
      determinants of diabetes and health along with individual factors. The purpose of
      this literature review is to examine current understanding of the social
      determinants affecting diabetes and health. A search of medical and nursing
      literature was conducted using PubMed, PsychInfo, CINAHL and MEDLINE databases,
      selecting articles published between 2000 and 2013. Search terms included: type 2
      diabetes, social determinants, and health determinants. Inclusion criteria were:
      English language, human studies, social determinants of diabetes and health, and
      research in the United States. Additional search methods included reference
      chaining of the literature. Twenty research articles met the inclusion criteria
      for the review and analysis and included quantitative and qualitative methods.
      All studies selected for this review were descriptive in nature (n = 20). Fifteen
      studies were quantitative studies and five were qualitative studies. No
      intervention studies met inclusion criteria. Each study is summarized and
      critiqued. Study findings indicate that external or upstream factors consistently
      affect individuals diagnosed with diabetes, influencing self-management.
      Significant methodological limitations result directly from small sample sizes,
      convenience or nonprobability sampling, and low statistical power. 

PMID- 24936248
TI  - Functional foods-based diet as a novel dietary approach for management of type 2
      diabetes and its complications: A review.
AB  - Type 2 diabetes is a complicated metabolic disorder with both short- and long
      term undesirable complications. In recent years, there has been growing evidence
      that functional foods and their bioactive compounds, due to their biological
      properties, may be used as complementary treatment for type 2 diabetes mellitus.
      In this review, we have highlighted various functional foods as missing part of
      medical nutrition therapy in diabetic patients. Several in vitro, animal models
      and some human studies, have demonstrated that functional foods and
      nutraceuticals may improve postprandial hyperglycemia and adipose tissue
      metabolism modulate carbohydrate and lipid metabolism. Functional foods may also
      improve dyslipidemia and insulin resistance, and attenuate oxidative stress and
      inflammatory processes and subsequently could prevent the development of long
      term diabetes complications including cardiovascular disease, neuropathy,
      nephropathy and retinopathy. In conclusion available data indicate that a
      functional foods-based diet may be a novel and comprehensive dietary approach for
      management of type 2 diabetes. 

PMID- 24936252
TI  - Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes
      patient.
AB  - Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and
      carbohydrate metabolism resulting in hyperglycemia as a result of insulin
      resistance and inadequate insulin secretion. Although a wide variety of diabetes
      therapies is available, yet limited efficacy, adverse effects, cost,
      contraindications, renal dosage adjustments, inflexible dosing schedules and
      weight gain significantly limit their use. In addition, many patients in the
      United States fail to meet the therapeutic HbA1c goal of < 7% set by the American
      Diabetes Association. As such new and emerging diabetes therapies with different
      mechanisms of action hope to address some of these drawbacks to improve the
      patient with type 2 diabetes. This article reviews new and emerging classes,
      including the sodium-glucose cotransporter-2 inhibitors, 11beta-Hydroxysteroid
      dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein
      tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and
      glucokinase activators. These emerging diabetes agents hold the promise of
      providing benefit of glucose lowering, weight reduction, low hypoglycemia risk,
      improve insulin sensitivity, pancreatic beta cell preservation, and oral
      formulation availability. However, further studies are needed to evaluate their
      safety profile, cardiovascular effects, and efficacy durability in order to
      determine their role in type 2 diabetes management. 

PMID- 24936253
TI  - 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2?
AB  - Genetic linkage analyses, genome-wide association studies of single nucleotide
      polymorphisms, copy number variation surveys, and mutation screenings found the
      human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be
      associated with an exceptionally wide spectrum of disease susceptibilities.
      Hematopoietic traits of red and white blood cells (like erythrocytosis and
      myeloproliferative disease), autoimmune disorders (like type 1 diabetes, coeliac
      disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic
      antiphospholipid syndrome, lupus erythematosus, multiple sclerosis,
      hypothyroidism and vitiligo), also vascular pathology (like kidney glomerular
      filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels,
      retinal microcirculation problems, diastolic and systolic blood pressure and
      hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative
      conditions (like the polyglutamine-expansion disorder spinocerebellar ataxia type
      2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis,
      and progressive supranuclear palsy), and finally longevity were reported. Now it
      is important to clarify, in which ways the loss or gain of function of the
      locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to
      these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1
      dependent proliferation of white blood cells. Its null mutations in human and
      mouse are triggers of autoimmune traits and leukemia (acute lymphoblastic
      leukemia or chronic myeloid leukemia-like), while missense mutations were found
      in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and
      trophic receptor internalization. While its polyglutamine-expansion mediated gain
      of-function causes neuronal atrophy in human and mouse, its deletion leads to
      obesity and insulin resistance in mice. Thus, it is conceivable that the
      polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation
      mediated predisposition to autoimmune diseases that conspires with an ATXN2
      deficiency-mediated predisposition to lipid and glucose metabolism pathology. 

PMID- 24936254
TI  - Interrelationships between ghrelin, insulin and glucose homeostasis:
      Physiological relevance.
AB  - Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the
      stomach. Both acylated (AG) and unacylated (UAG) forms of ghrelin are found in
      the circulation. Initially, AG was considered as the only bioactive form of
      ghrelin. However, recent advances indicate that both AG and UAG exert distinct
      and common effects in organisms. Soon after its discovery, ghrelin was shown to
      promote appetite and adiposity in animal and human models. In response to these
      anabolic effects, an impressive number of elements have suggested the influence
      of ghrelin on the regulation of metabolic functions and the development of
      obesity-related disorders. However, due to the complexity of its biochemical
      nature and the physiological processes it governs, some of the effects of ghrelin
      are still debated in the literature. Evidence suggests that ghrelin influences
      glucose homeostasis through the modulation of insulin secretion and insulin
      receptor signaling. On the other hand, insulin was also shown to influence
      circulating levels of ghrelin. Here, we review the relationship between ghrelin
      and insulin and we describe the impact of this interaction on the modulation of
      glucose homeostasis. 

PMID- 24936256
TI  - Adipokines as a novel link between obesity and atherosclerosis.
AB  - The traditional perception of adipose tissue as a storage organ of fatty acids
      has been replaced by the notion that adipose tissue is an active endocrine organ,
      releasing various adipokines that are involved in the pathogenesis of obesity
      related metabolic disturbances. Obesity is a well-known risk factor for
      atherosclerosis, and accelerates atherosclerosis by many mechanisms such as
      increase in blood pressure and glucose level, abnormal lipid profiles, and
      systemic inflammation. Furthermore, growing evidence suggests that some
      adipokines directly mediate the process of atherosclerosis by influencing the
      function of endothelial cells, arterial smooth muscle cells, and macrophages in
      vessel walls. In obese patients, the secretion and coordination of such
      adipokines is abnormal, and the secretion of specific adipokines increases or
      decreases. Accordingly, the discovery of new adipokines and elucidation of their
      functions might lead to a new treatment strategy for metabolic disorders related
      to obesity, including cardiovascular diseases. 

PMID- 24936255
TI  - Clinical therapeutic strategies for early stage of diabetic kidney disease.
AB  - Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease,
      leading to end-stage renal disease and cardiovascular disease. The overall number
      of patients with DKD will continue to increase in parallel with the increasing
      global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has
      become preventable by controlling conventional factors, including hyperglycemia
      and hypertension, with multifactorial therapy; however, the remaining risk of DKD
      progression is still high. In this review, we show the importance of targeting
      remission/regression of microalbuminuria in type 2 diabetic patients, which may
      protect against the progression of DKD and cardiovascular events. To achieve
      remission/regression of microalbuminuria, several steps are important, including
      the early detection of microalbuminuria with continuous screening, targeting
      HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors
      to control blood pressure, the use of statins or fibrates to control
      dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is
      therefore an important therapeutic goal, and the absence of microalbuminuria
      could be a pivotal biomarker of therapeutic success in diabetic patients. Other
      therapies, including vitamin D receptor activation, uric acid-lowering drugs, and
      incretin-related drugs, may also be promising for the prevention of DKD
      progression. 

PMID- 24936257
TI  - Adrenomedullin and diabetes.
AB  - Adrenomedullin (ADM) is a peptide hormone widely expressed in different tissues,
      especially in the vasculature. Apart from its vasodilatatory and hypotensive
      effect, it plays multiple roles in the regulation of hormonal secretion, glucose
      metabolism and inflammatory response. ADM regulates insulin balance and may
      participate in the development of diabetes. The plasma level of ADM is increased
      in people with diabetes, while in healthy individuals the plasma ADM
      concentration remains low. Plasma ADM levels are further increased in patients
      with diabetic complications. In type 1 diabetes, plasma ADM level is correlated
      with renal failure and retinopathy, while in type 2 diabetes its level is linked
      with a wider range of complications. The elevation of ADM level in diabetes may
      be due to hyperinsulinemia, oxidative stress and endothelial injury. At the same
      time, a rise in plasma ADM level can trigger the onset of diabetes. Strategies to
      reduce ADM level should be explored so as to reduce diabetic complications. 

PMID- 24936259
TI  - Diabetes, sleep apnea, obesity and cardiovascular disease: Why not address them
      together?
AB  - Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most
      common diseases encountered by the worldwide population, with high social and
      economic burdens. Significant emphasis has been placed on obtaining blood
      pressure, body mass index, and placing importance on screening for signs and
      symptoms pointing towards cardiovascular disease. Symptoms related to sleep, or
      screening for sleep apnea has been overlooked by cardiac, diabetic, pulmonary and
      general medicine clinics despite recommendations for screening by several
      societies. In recent years, there is mounting data where obesity and obstructive
      sleep apnea sit at the epicenter and its control can lead to improvement and
      prevention of diabetes and cardiovascular complications. This editorial raises
      questions as to why obstructive sleep apnea screening should be included as yet
      another vital sign during patient initial inpatient or outpatient visit. 

PMID- 24936258
TI  - Diabetes and cancer: Associations, mechanisms, and implications for medical
      practice.
AB  - Both diabetes mellitus and cancer are prevalent diseases worldwide. It is evident
      that there is a substantial increase in cancer incidence in diabetic patients.
      Epidemiologic studies have indicated that diabetic patients are at significantly
      higher risk of common cancers including pancreatic, liver, breast, colorectal,
      urinary tract, gastric and female reproductive cancers. Mortality due to cancer
      is moderately increased among patients with diabetes compared with those without.
      There is increasing evidence that some cancers are associated with diabetes, but
      the underlying mechanisms of this potential association have not been fully
      elucidated. Insulin is a potent growth factor that promotes cell proliferation
      and carcinogenesis directly and/or through insulin-like growth factor 1 (IGF-1).
      Hyperinsulinemia leads to an increase in the bioactivity of IGF-1 by inhibiting
      IGF binding protein-1. Hyperglycemia serves as a subordinate plausible
      explanation of carcinogenesis. High glucose may exert direct and indirect effects
      upon cancer cells to promote proliferation. Also chronic inflammation is
      considered as a hallmark of carcinogenesis. The multiple drugs involved in the
      treatment of diabetes seem to modify the risk of cancer. Screening to detect
      cancer at an early stage and appropriate treatment of diabetic patients with
      cancer are important to improve their prognosis. This paper summarizes the
      associations between diabetes and common cancers, interprets possible mechanisms
      involved, and addresses implications for medical practice. 

PMID- 24936260
TI  - Emerging role of protein kinase C in energy homeostasis: A brief overview.
AB  - Protein kinase C-beta (PKCbeta), a member of the lipid-activated serine/threonine
      PKC family, has been implicated in a wide range of important cellular processes.
      Very recently, the novel role of PKCbeta in the regulation of triglyceride
      homeostasis via regulating mitochondrial function has been explored. In this
      review, I aim to provide an overview of PKCbeta regarding regulation by lipids
      and recently gained knowledge on its role in energy homeostasis. Alterations in
      adipose PKCbeta expression have been shown to be crucial for diet-induced obesity
      and related metabolic abnormalities. High-fat diet is shown to induce PKCbeta
      expression in white adipose tissue in an isoform- and tissue-specific manner.
      Genetically manipulated mice devoid of PKCbeta are lean with increased oxygen
      consumption and are resistant to high-fat diet-induced obesity and hepatic
      steatosis with improved insulin sensitivity. Available data support the model in
      which PKCbeta functions as a "diet-sensitive" metabolic sensor whose induction in
      adipose tissue by high-fat diet is among the initiating event disrupting
      mitochondrial homeostasis via intersecting with p66(Shc) signaling to amplify
      adipose dysfunction and have systemic consequences. Alterations in PKCbeta
      expression and/or function may have important implications in health and disease
      and warrants a detailed investigation into the downstream target genes and the
      underlying mechanisms involved. Development of drugs that target the PKCbeta
      pathway and identification of miRs specifically controlling PKCbeta expression
      may lead to novel therapeutic options for treating age-related metabolic disease
      including fatty liver, obesity and type 2 diabetes. 

PMID- 24936261
TI  - Diabetic nephropathy and inflammation.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal failure
      worldwide. Besides, diabetic nephropathy is associated with cardiovascular
      disease, and increases mortality of diabetic patients. Several factors are
      involved in the pathophysiology of DN, including metabolic and hemodynamic
      alterations, oxidative stress, and activation of the renin-angiotensin system. In
      recent years, new pathways involved in the development and progression of
      diabetic kidney disease have been elucidated; accumulated data have emphasized
      the critical role of inflammation in the pathogenesis of diabetic nephropathy.
      Expression of cell adhesion molecules, growth factors, chemokines and pro
      inflammatory cytokines are increased in the renal tissues of diabetic patients,
      and serum and urinary levels of cytokines and cell adhesion molecules, correlated
      with albuminuria. In this paper we review the role of inflammation in the
      development of diabetic nephropathy, discussing some of the major inflammatory
      cytokines involved in the pathogenesis of diabetic nephropathy, including the
      role of adipokines, and take part in other mediators of inflammation, as adhesion
      molecules. 

PMID- 24936262
TI  - Canagliflozin-current status in the treatment of type 2 diabetes mellitus with
      focus on clinical trial data.
AB  - Canagliflozin (CFZ) is a member of new class of glucose lowering agents, sodium
      glucose co-transporter (SGLT) inhibitors, which got approval by food and drug
      administration. It has insulin independent action by blocking the transporter
      protein SGLT2 in the kidneys, resulting in urinary glucose excretion and
      reduction in blood glucose levels. In clinical trials, CFZ significantly
      decreased HbA1c level when administered either as monotherapy or as combined
      therapy with other anti-diabetic drugs. Intriguingly, it showed additional
      benefits like weight reduction and lowering of blood pressure. The commonly
      observed side effects were urinary and genital infections. It has exhibited
      favorable pharmacokinetic and pharmacodynamic profiles even in patients with
      renal and hepatic damage. Hence, this review purports to outline CFZ as a newer
      beneficial drug for type 2 diabetes mellitus. 

PMID- 24936263
TI  - Impact of chronic disease self-management programs on type 2 diabetes management
      in primary care.
AB  - AIM: To assess the effectiveness of the Chronic Disease Self-Management Program
      (CDSMP) on glycated hemoglobin A1c (HbA1c) and selected self-reported measures.
      METHODS: We compared patients who received a diabetes self-care behavioral
      intervention, the CDSMP developed at the Stanford University, with controls who
      received usual care on their HbA1c and selected self-reported measures, including
      diabetes self-care activities, health-related quality of life (HRQOL), pain and
      fatigue. The subjects were a subset of participants enrolled in a randomized
      controlled trial that took place at seven regional clinics of a university
      affiliated integrated healthcare system of a multi-specialty group practice
      between January 2009 and June 2011. The primary outcome was change in HbA1c from
      randomization to 12 mo. Data were analyzed using multilevel statistical models
      and linear mixed models to provide unbiased estimates of intervention effects.
      RESULTS: Demographic and baseline clinical characteristics were generally
      comparable between the two groups. The average baseline HbA1c values in the CDSMP
      and control groups were 9.4% and 9.2%, respectively. Significant reductions in
      HbA1c were seen at 12 mo for the two groups, with adjusted changes around 0.6% (P
      < 0.0001), but the reductions did not differ significantly between the two groups
      (P = 0.885). Few significant differences were observed in participants' diabetes
      self-care activities. No significant differences were observed in the
      participants' HRQOL, pain, or fatigue measures. CONCLUSION: The CDSMP
      intervention may not lower HbA1c any better than good routine care in an
      integrated healthcare system. More research is needed to understand the benefits
      of self-management programs in primary care in different settings and
      populations.

PMID- 24936264
TI  - MERS-CoV: Bridging the Knowledge Gaps.

PMID- 24936266
TI  - Knowledge and Attitudes of Oman Medical Specialty Board Residents towards
      Evidence-Based Medicine.
AB  - OBJECTIVE: This study aims to evaluate the knowledge and attitudes of Oman
      Medical Specialty Board (OMSB) residents towards Evidence-Based Medicine (EBM).
      METHODS: This cross sectional study was conducted on all OMSB residents through a
      self-administered online questionnaire between October 2012 and March 2013. An
      electronic survey was designed to identify and determine residents' knowledge and
      attitudes toward the use of EBM. RESULTS: The survey was completed by 93 (21%)
      OMSB residents, 76 (82%) of whom took part in continuing education courses and 50
      (54%) belonged to professional practice-oriented organizations. On average, the
      residents were reportedly involved in patient care for approximately 70%
      (Standard Deviation [SD] 17%) of their time, while 14% (SD 12%) participated in
      research activities. The results showed that 53 respondents (57%) were competent
      users of medical search engines compared to 23 residents (25%) who rated their
      skills as neutral. Sixteen percent of the respondents strongly agreed and 46%
      only agreed that the facility supports the use of current research in practice.
      Fourteen percent strongly agreed and fifty-three percent only agreed that the
      foundation of EBM is part of OMSB academic preparation. On the other hand, 17% of
      the respondents thought that insufficient time is always a barrier against EBM,
      while another 27% perceived insufficient time as a usual barrier. The lack of
      information resources was reported to always be a barrier in 11% of the
      respondents while 32% thought that it usually acts as a barrier. CONCLUSION: Time
      constraints and skills in EBM were found to be the two major obstacles. This
      study was, however, limited by the low response rate of the survey; thus larger
      studies with a previously validated questionnaire should be conducted in the
      future.

PMID- 24936265
TI  - Vitamin k dependent proteins and the role of vitamin k2 in the modulation of
      vascular calcification: a review.
AB  - Vascular calcification, a cause of cardiovascular morbidity and mortality, is an
      actively regulated process involving vitamin K dependent proteins (VKDPs) among
      others. Vitamin K is an essential micronutrient, present in plants and animal
      fermented products that plays an important role as a cofactor for the post
      translational gamma-carboxylation of glutamic acid residues in a number of
      proteins. These VKDPs require carboxylation to become biologically active, and
      they have been identified as having an active role in vascular cell migration,
      angiogenesis and vascular calcification. This paper will review the process of
      vascular calcification and delineate the role that vitamin K2 plays in the
      modulation of that process, through the activation of VKDPs. One such VKDP is
      Matrix Gla Protein (MGP), which when activated inhibits osteogenic factors,
      thereby inhibiting vascular and soft tissue calcification. 

PMID- 24936268
TI  - Predictors of Vaccination Card Retention in Children 12-59 months old in Karachi,
      Pakistan.
AB  - OBJECTIVE: To determine the factors associated with retaining the vaccination
      card among care takers of 12-59 months old children in Karachi, Pakistan.
      METHODS: This was an analytical cross-sectional study in Karachi. Households were
      randomly selected throughout a multistage cluster sampling technique. Data was
      collected for 504 children of 12- 59 months of age. Questionnaire was
      administered to caretakers to gather information regarding the children's
      vaccination status, socio-demographic characteristics and reviewing their
      vaccination cards. Statistical analysis was done by SPSS 19 using logistic
      regression. RESULTS: Among 462 vaccinated children, caretakers of 33% provided
      vaccination cards. Odds of card retention decrease if the caretaker has a large
      household i.e., >5 people sharing one room (AOR 0.277, 95% CI: 0.096, 0.797) and
      if the child is of four to five years of age (AOR 0.544, 95% CI: 0.305, 0.970).
      Gender of the child, and the caretaker's education and access to electronic media
      were not significant predictors of vaccination card retention in our study.
      CONCLUSION: Our study showed that vaccination card retention for children 12-59
      months of age was low (33%) in Karachi. There is a need to educate caretakers of
      young children regarding the importance of keeping vaccination card and to
      disseminate this information through healthcare providers. Improving vaccination
      card retention is one of the key measures which will help towards accurately
      estimating coverage and to inform health policy decisions.

PMID- 24936267
TI  - Calcium intervention ameliorates experimental model of multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is the most common inflammatory disease of the
      CNS. Experimental autoimmune encephalomyelitis (EAE) is a widely used model for
      MS. In the present research, our aim was to test the therapeutic efficacy of
      Calcium (Ca) in an experimental model of MS. METHODS: In this study the
      experiment was done on C57BL/6 mice. EAE was induced using 200 MUg of the MOG35
      55 peptide emulsified in CFA and injected subcutaneously on day 0 over two flank
      areas. In addition, 250 ng of pertussis toxin was injected on days 0 and 2. In
      the treatment group, 30 mg/kg Ca was administered intraperitoneally four times at
      regular 48 hour intervals. The mice were sacrificed 21 days after EAE induction
      and blood samples were taken from their hearts. The brains of mice were removed
      for histological analysis and their isolated splenocytes were cultured. RESULTS:
      Our results showed that treatment with Ca caused a significant reduction in the
      severity of the EAE. Histological analysis indicated that there was no plaque in
      brain sections of Ca treated group of mice whereas 4 +/- 1 plaques were detected
      in brain sections of controls. The density of mononuclear infiltration in the CNS
      of Ca treated mice was lower than in controls. The serum level of Nitric Oxide in
      the treatment group was lower than in the control group but was not significant.
      Moreover, the levels of IFN-gamma in cell culture supernatant of splenocytes in
      treated mice were significantly lower than in the control group. CONCLUSION: The
      data indicates that Ca intervention can effectively attenuate EAE progression.

PMID- 24936269
TI  - The Effect of Vitamin B12 Infusion on Prevention of Nitrous Oxide-induced
      Homocysteine Increase: A Double-blind Randomized Controlled Trial.
AB  - OBJECTIVE: Nitrous oxide is a common inhalation anesthetic agent in general
      anesthesia. While it is widely accepted as a safe anesthetic agent, evidence
      suggests exposure to this gas, leads to hyperhomocysteinemia. The present study
      aimed to evaluate the effects of single-dose intravenous infusions of vitamin
      B12, before and after the induction of nitrous oxide anesthesia on homocysteine
      levels after the surgery. METHODS: This double-blind randomized controlled trial
      was conducted on 60 patients who were scheduled for elective surgery under
      general anesthesia, presumably lasting for more than two hours. The subjects were
      randomly allocated to three groups of 20. For the first group, vitamin B12
      solution (1 mg/100 ml normal saline) and 100 ml of normal saline (placebo), were
      infused before and after the induction of anesthesia, respectively. The second
      group received placebo and vitamin B12 infusion before and after the induction of
      anesthesia, respectively. The third group received placebo infusions at both
      times. Homocysteine levels were measured before and 24 hours after the surgery.
      RESULTS: The mean homocysteine and vitamin B12 levels were significantly
      different within the three groups (p<0.001). In patients who had been infused
      with vitamin B12 before the surgery, homocysteine levels were significantly lower
      than the other two groups. In the placebo group, homocysteine levels
      significantly increased after the surgery. CONCLUSION: Nitrous oxide causes
      hyperhomocysteinemia after general anesthesia. Since vitamin B12 infusion is a
      safe and inexpensive method to decrease homocysteine levels in these patients, it
      may be recommended for patients undergoing nitrous oxide anesthesia to be used
      before induction of anesthesia.

PMID- 24936270
TI  - Prospective study on prevalence and risk factors of postpartum depression in Al
      dakhliya governorate in oman.
AB  - OBJECTIVES: Postnatal Depression (PND) is a major health problem. It has a
      serious impact on the mother, her child and family. Studies have shown wide
      diversity of its prevalence across different cultures. Its epidemiology and its
      associated risk factors in Oman remain unknown. The objectives of this study were
      to estimate the prevalence of PND in the Al-Dakhliya governorate and to identify
      the risk factors contributing to the development of PND. METHODS: A total of 282
      Omani women who gave birth in September 2010 were part of a prospective study
      conducted in Al-Dakhliya governorate. An Arabic version of the Edinburgh
      Postnatal Depression Scale (EPDS) was used to assess the PND symptoms. Negative
      binomial regression model was used to identify the independent predictors of
      outcome (EPDS scores at two and eight weeks post-delivery) due to the non-normal
      distribution of the EPDS scores. RESULTS: The study results showed that at two
      weeks, 13.5% of mothers and 10.6% at eight weeks had EPDS scores of 13. Bahla
      district was found to have the highest number of depression scores among the
      other six districts in the governorate. It was found that mothers less than 25
      years of age were more likely to report high EPDS scores. The independent
      predictor was work difficulties both at two and eight weeks postpartum (p=0.001
      and p=0.019, respectively). At two weeks postpartum, significant association was
      also found between depression scores and conflict with a family member (p=0.017),
      and sickness of a family member (p=0.010). There was no significant association
      between EPDS scores and socio-demographic, obstetric or other clinical factors.
      CONCLUSION: This study is among the few studies looking at PND in the Middle East
      and shows on average 12% of Omani women are at a high risk of developing PND
      (EPDS scores of >=13). Although the study findings were based on an unvalidated
      version of EPDS for Omani women, they can be used as a basis for further
      research.

PMID- 24936271
TI  - Prevalence Pattern of Risk Factors for Coronary Artery Disease among Patients
      Presenting for Coronary Artery Bypass Grafting in Oman.
AB  - OBJECTIVES: To identify the pattern of prevalence of risk factors in patients
      presenting for coronary artery bypass grafting at a single center in Oman.
      METHODS: All patients who had coronary artery bypass grafting between March 2008
      to March 2010 were included and data were obtained from history and laboratory
      investigations. The prevalence rates of eight conventional risk factors are
      presented as a retrospective single center observational study. RESULTS: Out of
      146 total patients, 107 (73.29%) were male. The age ranged from 31 to 87 years
      old. The mean age was 58.18 +/- 10.08 years (males = 56.81 +/- 10.42, females =
      61.95 +/- 7.97). Hypertension was present in 119 patients (81.51%), 115 patients
      (78.77%) had dyslipidemia, 107 patients (73.29%) were male, 79 patients (54.11%)
      had diabetes mellitus, 70 patients (47.95%) were over the age of 60 years, 41
      patients (28.08%) gave a history of smoking, 31 patients (21.23%) were obese, and
      19 patients (13.01%) gave a positive family history. CONCLUSIONS: The most common
      risk factor was hypertension, followed by dyslipidemia, male gender, diabetes
      mellitus, old age, smoking, obesity and positive family history; 87.7% had three
      or more risk factors. The females in this study were older than the males and had
      more risk factors at presentation. The most common combination of factors seen
      together was diabetes, hypertension, dyslipidemia and male gender.

PMID- 24936272
TI  - Effect of locally administered ciliary neurotrophic factor on the survival of
      transected and repaired adult sheep facial nerve.
AB  - OBJECTIVE: to determine whether the administration of Ciliary Neurotrophic Factor
      (CNTF) at the site of repaired facial nerve enhances regeneration in the adult
      sheep model. METHODS: Ten adult sheep were divided into 2 groups: control and
      study group (CNTF group). In the CNTF group, the buccal branch of the facial
      nerve was transected and then repaired by epineural sutures. CNTF was injected
      over the left depressor labii maxillaris muscle in the vicinity of the transected
      and repaired nerve for 28 days under local anesthesia. In the CNTF group, the
      sheep were again anesthetized after nine months and the site of facial nerve
      repair was exposed. Detailed electrophysiological, tension experiments and
      morphometric studies were carried out and then analyzed statistically. RESULTS:
      The skin CV min, refractory period, Jitter and tension parameters were marginally
      raised in the CNTF group than the control but the difference was statistically
      insignificant between the two groups. Morphometric indices also did not show any
      significant changes in the CNTF group. CONCLUSION: CNTF has no profound effect on
      neuronal regeneration of adult sheep animal model. KEYWORDS: CNTF; Neurtrophic
      factors; Sheep; Facial nerve; Regeneration.

PMID- 24936273
TI  - Uterine artery embolization: exploring new dimensions in obstetric emergencies.
AB  - The role of transcatheter arterial embolization in the management of obstetric
      emergencies is relatively new and not so commonly used. In the following series,
      the efficacy of this technique in situations such as scar site ectopic pregnancy,
      antepartum and postpartum obstetric hemorrhage, especially in the presence of
      coagulation derangement is presented. 

PMID- 24936274
TI  - Avulsion fracture of the anterior inferior iliac spine mimicking a bone tumor: a
      case report.
AB  - This is a case of a 17-year-old boy who was admitted to the clinic suffering from
      right hip-inguinal region pain which began after a soccer match. He had an
      avulsion fracture in the anterior inferior iliac spine and CT/MR images showed
      similarities to a bone tumor. These fractures are especially seen in the
      apophyses which are within the ossification process. The radiological appearance
      of these fractures during the healing period may be involved with bone tumors. In
      the control MRI of the patient after one year, the fracture was almost healed
      completely. Treatment is generally conservative. Good results have been reported
      with rest, analgesic and anti-inflammatory drugs. Familiarity with radiological
      findings of these avulsion fractures in this region not only protects the patient
      from invasive procedures but also avoids the involvement of the practitioner in
      legal consequences resulting from a misdiagnosis of sarcoma. 

PMID- 24936275
TI  - Late presentation of congenital diaphragmatic hernia: a case report.
AB  - Delayed herniation of the abdominal contents through a congenital diaphragmatic
      hernia may occur beyond the neonatal period. This report describes a 9-week-old
      female baby who presented with excessive crying, irritability and respiratory
      distress secondary to late presentation of left-sided congenital diaphragmatic
      hernia. The chest radiograph showed tension gastrothorax. She underwent surgical
      reduction of the hernia. She made an excellent recovery and was discharged a few
      days after the operation. It is assumed that sudden increase of the intra
      abdominal pressure caused herniation of abdominal content through a pre-existing
      diaphragmatic defect. This report aims to increase the awareness of this
      condition among physicians and pediatric surgeons to allow early diagnosis and
      management. 

PMID- 24936277
TI  - Endometriosis after surgical menopause mimicking pelvic malignancy: surgeons'
      predicament.
AB  - Prevalence of persistent endometriosis in women after menopause without any
      hormonal replacement therapy is very rare. This is a case of a woman with
      previous history of total hysterectomy and bilateral salpingo-oophorectomy for
      endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass,
      and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is
      the first case report with a unique mode of presentation wherein the patient
      presented with hemoperitoneum requiring emergency embolization of the vessel to
      stabilize the patient. She underwent en bloc resection of the tumor with high
      anterior resection of the rectum. Histopathology confirmed endometriosis. 

PMID- 24936276
TI  - Lymphoma presenting as severe left ventricular systolic dysfunction: a case
      report.
AB  - Lymphoma involving the heart is rare. This is a case report on non-Hodgkin
      lymphoma where the patient presented for the first time with heart failure and
      severe left ventricular systolic dysfunction due to lymphoma infiltrating the
      heart muscle and had simultaneous bilateral involvement of kidneys. This type of
      presentation has never been described in world literature and is the first
      reported case. 

PMID- 24936278
TI  - Determinants of diabetes and hypertension control in ambulatory healthcare in Al
      ain, United arab emirates.
AB  - OBJECTIVES: This study aims to study determinants for the control of diabetes and
      hypertension in Al Ain Ambulatory Healthcare patients. METHOD: This is a cross
      sectional observational study of patients attending ambulatory healthcare centers
      in Al Ain, United Arab Emirates in 2009. From a yearly audit evaluating the care
      of patients with diabetes and hypertension, the determinants for improved
      diabetes and hypertension outcomes were identified from a total of 512 patients
      and its association with glycemic and blood pressure control were studied.
      RESULTS: From all variables studied, only the clinic where the patient was
      treated helped predict both improved blood sugar and blood pressure control. For
      patients with diabetes, poor control the year before (p<0.001), the number of
      chronic disease clinic visits (p=0.042) and triglyceride levels (p=0.007)
      predicted worse control of diabetes. A predictor of poor control of blood
      pressure (p<0.001) for patients with hypertension was poor control of blood
      pressure in the year before. CONCLUSION: In this population, the healthcare
      system and the team played major roles as determinants in the control of
      patient's diabetes and blood pressure more than any of the other factors
      examined.

PMID- 24936279
TI  - Clinical and histological profile of surgically managed benign adnexal masses.
AB  - OBJECTIVE: To study the clinical and histological nature of benign adnexal masses
      managed surgically. METHODS: A retrospective descriptive study in a teaching
      hospital in Oman of all the women who had surgical management of benign adnexal
      masses from January 2008 to May 2012. Data pertaining to age, parity, presenting
      symptoms, imaging and tumor markers performed and the surgical intervention done
      on those women with benign adnexal masses was collected from the electronic
      health records of the patients. RESULTS: There were 198 women during this period
      operated for benign adnexal masses. The most common benign neoplasm was mature
      teratoma of the ovary followed by endometriosis. Conservative surgery in the form
      of ovarian cystectomy was necessary in three fourths of women and in about just
      less than 50% of women, the procedure was completed laparoscopically. CONCLUSION:
      The most common benign tumor was teratoma but laparoscopic approach, which is the
      standard of care in these women, was possible only in just about 50% of the
      women.

PMID- 24936280
TI  - Diarrhea associated with retroperitoneal tumor.

PMID- 24936281
TI  - Demographic and clinical characteristic of type 1 diabetes mellitus in omani
      children: single center experience.

PMID- 24936282
TI  - AIs Scientific Production Problem-Oriented? Diabetes and Ramadan as an Example.

PMID- 24936283
TI  - Outcome of trans-axillary approach for surgical decompression of thoracic outlet:
      a retrospective study in a tertiary care hospital.
AB  - OBJECTIVE: The aim of this study was to evaluate the trans-axillary surgical
      approach in patients with thoracic outlet syndrome. METHODS: This retrospective
      study is comprised of data acquired from January 1998 until Oct 2008. Case
      histories of all the patients were reviewed from the Medical Records Department
      of Sher-i-Kashmir Institute. Relevant information and follow-up of the patients
      was carried out by examining the relevant clinical notes available by telephone
      interviews and personal contact whenever possible. All data was compiled and
      analyzed statistically. RESULTS: There were a total of 139 patients. The female:
      male ratio was about 6:1. Pain was the most common presenting symptom followed by
      weakness and parasthesia. Nerve conduction velocity was abnormal in 111 patients.
      Twenty-eight patients had abnormal Doppler study of subclavian vessels.
      Preoperative symptoms persisted in 13 patients. Overall, 126 patients showed
      improvement in symptoms and no recurrence or persistence of symptoms on follow-up
      examination. CONCLUSION: Trans-axillary approach provides a good exposure and
      cosmesis in patients with thoracic outlet syndrome. It should be considered as
      the gold standard in the management of thoracic outlet syndrome.

PMID- 24936284
TI  - Emotions and emotion regulation in survivors of childhood sexual abuse: the
      importance of "disgust" in traumatic stress and psychopathology.
AB  - BACKGROUND: Childhood sexual abuse (CSA) has the potential to compromise socio
      emotional development of the survivor resulting in increased vulnerability to
      difficulties regulating emotions. In turn, emotion regulation is thought to play
      a key part in a number of psychological disorders which CSA survivors are at
      increased risk of developing. A better understanding of the basic emotions
      experienced in this population and emotion regulation strategies will inform
      current treatment. OBJECTIVE: This paper examines the relationships between type
      of emotions experienced, emotion regulation strategies, and psychological trauma
      symptoms in a sample of survivors of CSA. METHOD: A consecutive case series of
      CSA survivors (n=109) completed the Basic Emotions Scale (BES)-Weekly, General,
      and Coping versions; the Regulation of Emotions Questionnaire; the Post-traumatic
      Stress Checklist-Civilian Version (PCL-C); and the Clinical Outcomes in Routine
      Evaluation Outcome Measure. RESULTS: Significantly higher levels of disgust than
      other levels of emotions were reported on the weekly version of the BES. In
      addition, significantly higher levels of disgust and lower levels of happiness
      were reported on the BES-General subscale. Regression analyses revealed that
      sadness, fear, disgust, and external dysfunctional coping strategies predicted
      global post-traumatic stress disorder and re-experiencing symptomatology measured
      by the PCL-C. Global distress, as measured by CORE, was predicted by the emotions
      of sadness, disgust, and low happiness, as well as dysfunctional regulatory
      strategies. In addition, preliminary exploratory factor analyses supported the
      structure of all three versions of the BES, with disgust explaining the largest
      percentage of variance, followed by happiness. CONCLUSIONS: The findings
      highlight the utility of profiling basic emotions in understanding the strong
      associations between emotional phenomena, particularly the emotion of disgust and
      psychopathology in CSA survivors.

PMID- 24936285
TI  - Rape-related symptoms in adolescents: short- and long-term outcome after
      cognitive behavior group therapy.
AB  - BACKGROUND: Efficacy studies on treatment in adolescent victims of single rape
      are lacking, even though sexual victimization is most likely to occur during
      adolescence and despite the fact that adolescents are at risk to develop
      subsequent posttraumatic stress disorder. AIM: The aim of this prospective
      observational study was to evaluate the short- and long-term outcomes of a nine
      session cognitive behavior group therapy (STEPS), including a parallel six
      session parents' group on rape-related symptomatology in female adolescents (13
      18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo,
      cognitive restructuring, and relapse prevention. METHODS: Fifty-five female
      adolescents with mental health problems due to single rape, but without prior
      sexual trauma, received STEPS while their parents participated in a support
      group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms
      using self-report questionnaires prior to and directly after treatment, and at 6
      and 12 months follow-up. RESULTS: Repeated measures analysis showed a significant
      and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation,
      sexual concerns, and behavior problems directly after treatment, which maintained
      at 12 months follow-up. Time since trauma did not influence the results. Dropout
      during STEPS was 1.8%. CONCLUSIONS: The results potentially suggest that the
      positive treatment outcomes at short- and long-term may be caused by STEPS. The
      encouraging findings need confirmation in future controlled studies on the
      effectiveness of STEPS because it may be possible that the treatment works
      especially well for more chronic symptoms, while the less chronic part of the
      sample showed considerable improvement on its own.

PMID- 24936286
TI  - My Corporis Fabrica: an ontology-based tool for reasoning and querying on complex
      anatomical models.
AB  - BACKGROUND: Multiple models of anatomy have been developed independently and for
      different purposes. In particular, 3D graphical models are specially useful for
      visualizing the different organs composing the human body, while ontologies such
      as FMA (Foundational Model of Anatomy) are symbolic models that provide a unified
      formal description of anatomy. Despite its comprehensive content concerning the
      anatomical structures, the lack of formal descriptions of anatomical functions in
      FMA limits its usage in many applications. In addition, the absence of connection
      between 3D models and anatomical ontologies makes it difficult and time-consuming
      to set up and access to the anatomical content of complex 3D objects. RESULTS:
      First, we provide a new ontology of anatomy called My Corporis Fabrica (MyCF),
      which conforms to FMA but extends it by making explicit how anatomical structures
      are composed, how they contribute to functions, and also how they can be related
      to 3D complex objects. Second, we have equipped MyCF with automatic reasoning
      capabilities that enable model checking and complex queries answering. We
      illustrate the added-value of such a declarative approach for interactive
      simulation and visualization as well as for teaching applications. CONCLUSIONS:
      The novel vision of ontologies that we have developed in this paper enables a
      declarative assembly of different models to obtain composed models guaranteed to
      be anatomically valid while capturing the complexity of human anatomy. The main
      interest of this approach is its declarativity that makes possible for domain
      experts to enrich the knowledge base at any moment through simple editors without
      having to change the algorithmic machinery. This provides MyCF software
      environment a flexibility to process and add semantics on purpose for various
      applications that incorporate not only symbolic information but also 3D geometric
      models representing anatomical entities as well as other symbolic information
      like the anatomical functions.

PMID- 24936287
TI  - Aromatase inhibitors-induced bone loss in early breast cancer.
AB  - Women with breast cancer have an increased prevalence and incidence of fractures.
      This increased risk of fracture has become most evident following the use of
      aromatase inhibitors (AIs) as standard adjuvant therapy. AI-induced bone loss
      occurs at more than twice the rate of physiologic postmenopausal bone loss.
      Moreover, peripheral quantitative computed tomography data indicate that effects
      of AIs on bone strength and on cortical bone have been substantially
      underestimated by dual-energy X-ray absorptiometry. All AIs have been associated
      with an increased fracture risk. The incidence of fractures is at least 33-43%
      higher in AI-treated patients than in tamoxifen-treated patients, and this
      increase in fracture risk is maintained at least for the duration of AI therapy.
      Over the last few years, clinical trials have established the effectiveness of
      bisphosphonates and denosumab to preserve and even increase bone mineral density
      (BMD) during adjuvant AIs. Most data have been obtained with zoledronic acid
      administered twice a year, which effectively maintains or increases BMD in women
      receiving AIs. In addition, zoledronic acid has been shown to delay disease
      recurrence and maybe prolong survival in women with hormone-responsive tumors,
      thereby providing an adjuvant antitumor benefit besides preserving BMD. It is
      likely that a combined fracture risk assessment will more accurately identify
      women with breast cancer who require bone protective therapy. The FRAX tool
      probably underestimates the net increase in fracture risk due to AI therapy.
      Recent guidelines for the prevention of AI-induced bone loss have adequately
      considered the presence of several established clinical risk factors for
      fractures, in addition to BMD, when selecting patients to be treated with
      inhibitors of bone resorption. 

PMID- 24936289
TI  - Modeling of electrohydrodynamic drying process using response surface
      methodology.
AB  - Energy consumption index is one of the most important criteria for judging about
      new, and emerging drying technologies. One of such novel and promising
      alternative of drying process is called electrohydrodynamic (EHD) drying. In this
      work, a solar energy was used to maintain required energy of EHD drying process.
      Moreover, response surface methodology (RSM) was used to build a predictive model
      in order to investigate the combined effects of independent variables such as
      applied voltage, field strength, number of discharge electrode (needle), and air
      velocity on moisture ratio, energy efficiency, and energy consumption as
      responses of EHD drying process. Three-levels and four-factor Box-Behnken design
      was employed to evaluate the effects of independent variables on system
      responses. A stepwise approach was followed to build up a model that can map the
      entire response surface. The interior relationships between parameters were well
      defined by RSM. 

PMID- 24936288
TI  - Antiosteoporotic effect of orally administered yolk-derived peptides on bone mass
      in women.
AB  - The main objective of this study was to verify the effect of oral intake of a
      yolk-derived peptide preparation (HYP) obtained by enzymatic hydrolysis of yolk
      water-soluble protein on bone markers and bone density in 65 perimenopausal women
      with an average age of 47.6 +/- 5.2 years. Subjects were divided into three
      groups, and then enrolled in a 6-month, randomized, double-blind clinical trial.
      Bone formation and resorption markers were measured at 0, 3, and 6 months, while
      bone mineral density (BMD) in the lumbar spines was measured at 0 and 6 months.
      Although the bone formation marker levels showed the similarity changes among the
      groups, bone resorption markers in the test HYP group were significantly
      decreased after 3 and 6 months in comparison to other groups (P < 0.05). After 6
      months, BMD in the test HYP group maintained at healthy numerical values whereas
      BMD values were decreased in other groups. Hence HYP would be an antiosteoporotic
      agent originated from natural food to maintain bone health, especially for women.

PMID- 24936290
TI  - Enhancing safety and shelf life of fresh-cut mango by application of edible
      coatings and microencapsulation technique.
AB  - Mango pulp is very perishable and so has a short shelf life, which both marketers
      and consumers would like to be longer. Manually sliced mango was treated by
      coating opuntia mucilage-rosemary oil (Mu + RO), 2 g rosemary oil microencapsul
      (ROM), and 2 g (ROM) plus (Mu + RO); the treated mango pieces were placed in
      plastic trays, and overwrapped with PVDC film and then stored at 6 degrees C.
      Changes in the quality parameters and activity of peroxidase (POD) enzyme were
      evaluated for 9 days of storage period. These treatments retarded loss of
      ascorbic acid and the drop in sensory acceptability, fewer changes in color,
      decreasing activity POD enzyme. These also inhibited the decay incidence and
      slowed microbial growth. The (Mu + RO) treatment was more effective in
      controlling postharvest quality as compared to the (ROM) treatment, but the data
      reveal that applying the compound treatment effectively prolongs the quality
      attributes and extends the storage life of sliced mango fruit. 

PMID- 24936292
TI  - Analysis of essential elements in Pito-a cereal food drink and its brands by the
      single-comparator method of neutron activation analysis.
AB  - Instrumental neutron activation analysis using the single-comparator method has
      been used for the multielement determination of essential elements in two main
      types of Pito brewed locally in Ghana. The precision and accuracy of the
      analytical method was validated and found to be within 10%. In all, eight
      different brands of Pito depending on the type of cereal crop used in brewing
      were analyzed for 13 different elements (Al, As, Ba, Cl, Co, Cu, Fe, K, Mg, Mn,
      Na, Si, and Zn). It was observed that all brands were particularly enriched in
      nutrient elements Cl, Mg, and K. The rest were generally found in varying
      concentrations. As these elements are bioavailable in natural form, perhaps in
      combination with organic constituents, they are likely to be easily digested and
      assimilated by the human body. Arsenic, a toxic element, was found in
      insignificant amounts suggesting that it was within safe limits. 

PMID- 24936291
TI  - Protective effect of resveratrol against pressure overload-induced heart failure.
AB  - Transverse aortic constriction (TAC)-induced pressure overload (PO) causes
      adverse cardiac remodeling and dysfunction that progresses to heart failure (HF).
      The purpose of this study was to determine whether the potent antioxidant,
      resveratrol, significantly attenuates PO-induced HF in wild-type mice. Male
      C57BL6 mice were subjected to either sham or TAC surgery. One group of TAC mice
      was given daily resveratrol treatment. Echocardiographic, biometric, and
      immunohistological analyses were performed on the three groups of mice. All
      echocardiographic parameters demonstrated significantly greater adverse cardiac
      remodeling and dysfunction in the TAC compared to the sham mice. Increases in the
      ratios of heart weight (HW)/body weight (BW) and lung weight (LW)/BW and a sharp
      decline in the percentage of ejection fraction and fractional shortening were
      found in TAC relative to sham mice. Likewise, the TAC protocol increased markers
      of oxidative stress, cardiac hypertrophy, inflammation, fibrosis, hypoxia, and
      apoptosis. These pathological changes were significantly attenuated by
      resveratrol treatment. Resveratrol treatment significantly attenuates the adverse
      cardiac remodeling and dysfunction produced by the TAC protocol in C57/BL6 mice
      and this activity is mediated, at least in part, by the inhibition of oxidative
      stress and inflammation indicating a therapeutic potential of resveratrol in HF. 

PMID- 24936293
TI  - Survey of volatile substances in kitchen utensils made from acrylonitrile
      butadiene-styrene and acrylonitrile-styrene resin in Japan.
AB  - Residual levels of 14 volatile substances, including 1,3-butadiene,
      acrylonitrile, benzene, ethylbenzene, and styrene, in 30 kitchen utensils made
      from acrylonitrile-butadiene-styrene resin (ABS) and acrylonitrile-styrene resin
      (AS) such as slicers, picks, cups, and lunch boxes in Japan were simultaneously
      determined using headspace gas chromatography/mass spectroscopy (HS-GC/MS). The
      maximum residual levels in the ABS and AS samples were found to be 2000 and 2800
      MUg/g of styrene, respectively. The residual levels of 1,3-butadiene ranged from
      0.06 to 1.7 MUg/g in ABS, and three of 15 ABS samples exceeded the regulatory
      limit for this compound as established by the European Union (EU). The residual
      levels of acrylonitrile ranged from 0.15 to 20 MUg/g in ABS and from 19 to 180
      MUg/g in AS. The levels of this substance in seven ABS and six AS samples
      exceeded the limit set by the U.S. Food and Drug Administration (FDA).
      Furthermore, the levels of acrylonitrile in three AS samples exceeded the
      voluntary standard established by Japanese industries. These results clearly
      indicate that the residual levels of some volatile compounds are still high in
      ABS and AS kitchen utensils and further observations are needed. 

PMID- 24936294
TI  - Solar drying and organoleptic characteristics of two tropical African fish
      species using improved low-cost solar driers.
AB  - This study was done to evaluate the drying performance, efficiency, and
      effectiveness of five different types of improved low-cost solar driers in terms
      of moisture loss from two tropical African fish species Clarias gariepinus
      (African sharp tooth catfish) and Oreochromis niloticus (Nile tilapia) and
      testing the organoleptic characteristics of the dried samples. The driers used
      were made from plastic, aluminum, glass, glass with black igneous stone, and
      mosquito net, with traditional direct open-sun drying as a control. A significant
      (P < 0.05) decrease in weight resulting from moisture loss in the two fish
      species was observed in all the driers, with the highest reduction occurring in
      the glass drier containing black stone. The rate of weight loss was faster in the
      first 4 days of drying with black stone-inserted glass drier showing the fastest
      drying rate with a constant weight in C. gariepinus attained on the 11th day and
      in O. niloticus on the eighth day. The slowest drier was plastic where a constant
      weight of the species were recorded on and 13th day and 11th day, respectively.
      Volunteers were used to assess the organoleptic characteristics of the dried
      samples and they showed lowest acceptability for the open-sun drying, while
      samples from the glass drier containing black stone had the highest acceptability
      in terms of the taste, flavor, appearance, texture, odor, palatability, and shelf
      life. The low-cost solar driers were effective found in removing water from the
      fish resulting in significant loss of weight and moisture. The highest drying
      time, efficient performance, drying effectiveness, and high acceptability of the
      organoleptic parameters of the dried products from the black stone-inserted glass
      drier were due to the ability of the glass and the black stone to retain,
      transmit, and radiate heat to the fish sample all the time (day and night). These
      low-cost driers are simple to construct, materials for its construction readily
      available, easy to maintain and operate, hygienic in use, reliable, effective,
      occupies less area, dry products faster with increased shelf-life, save man-hour,
      user-friendly, use renewable energy, protect the drying samples from filthiness,
      wetness, and invasion by pests, insects, and microbes, with well-dried, high
      quality, and better preserved final products. The adoption and use any of these
      low-cost solar driers by artisanal fishermen and general household in sub-Saharan
      Africa will not only help in reducing post catch losses, but also ensure food
      safety and security as there is abundant solar energy in these sub-Saharan
      African tropical countries for the operation of the driers. 

PMID- 24936295
TI  - In vitro starch digestion in sorghum flour from Algerian cultivars.
AB  - This work aims to evaluate starch digestion in whole sorghum grains. Nine sorghum
      cultivars were sampled from the Sahara of Algeria. The structural characteristics
      of sorghum grains were measured. Total starch (TS) varied between 67.67% and
      74.82%, digestible starch (DS) between 64.34% and 69.70%, and resistant starch
      (RS) ranged from 2.55% to 7.98%. The kinetic of starch digestion displayed first
      order model. For all sorghum cultivars, starch were digested with different
      extents, DS at infinite time (D infinity) ranged from 52.58 to 102.13 g/100 g dry
      starch, while the hydrolysis index (HI) ranged from 41.55% to 76.93% and high
      average glycemic index (GIavg) ranged from 65.97 to 94.14. The results showed
      that there are differences in grain quality of Algerian sorghum cultivars. The
      starch fractions have acceptable nutritional value with good in vitro
      digestibility characteristics suitable for human health and nutrition. 

PMID- 24936297
TI  - Effects of processing on the proximate and metal contents in three fish species
      from Nigerian coastal waters.
AB  - The effects of culinary practices such as boiling, frying, and grilling on the
      proximate compositions and concentrations of metals (Cd, Pb, Cr, Zn, Fe, Cu, Mn,
      Ni, and Hg) in commonly consumed fish species from the Nigerian coastal waters
      were investigated. The selected fish species were Polydactylus quadratifilis,
      Chrysicthys nigrodigitatus and Cynoglossus senegalensis. The culinary practices
      lead to increased protein, fat, and ash contents and decreased moisture contents
      of these fish species. The culinary practices resulted significant increase in
      the concentrations of most of the studied metals and decrease in the
      concentrations of Fe, Cr, and Pb in some fish types. The concentrations and
      estimated dietary intakes of Cd, Pb, Cr, Zn, Fe, Cu, Mn, Ni, and Hg from
      consumption of the processed fish were within their statutory safe limits. The
      individual metal target hazard quotient (THQ) values and the total THQs were less
      than 1 which indicates that no health risks would arise from the long-term
      consumption of these fish species. 

PMID- 24936296
TI  - The role of N-glycosylation in kiwi allergy.
AB  - The physical, biochemical, and immunological characteristics of plant allergens
      have been widely studied, but no definite conclusion has been reached about what
      actually makes a protein an allergen. In this sense, N-glycosylation is an
      exclusive characteristic of plant allergens not present in mammals and it could
      be implied in allergenic sensitization. With this aim, we evaluated and compared
      the allergenic activity of the protein fraction and the N-glycan fraction of the
      thaumatin-like protein and the main kiwi allergen, Act d 2. The natural allergen,
      Act d 2, was deglycosylated by trifluoromethanesulfonic acid treatment; the N
      glycan fraction was obtained by extended treatment with proteinase K. N-glycan-
      and protein- fractions were recognized by specific IgE of kiwi-allergic patients.
      By contrast, the sugar moiety showed a reduced capacity to activate basophils and
      T cells, but not dendritic cells derived from patients' monocytes. Related to
      this, the production of cytokines such as IL6 and IL10 was increased by the
      incubation of dendritic cells with sugar moiety. Thus, the sugar moiety plays a
      significant role in sensitization, inducing the activation of antigen-presenting
      cells, but it is the protein fraction that is responsible for the allergic
      reactions. 

PMID- 24936298
TI  - Antioxidant capacity of hydrolyzed porcine tissues.
AB  - The antioxidative capacity of seven different porcine tissue hydrolysates (colon,
      appendix, rectum, pancreas, heart, liver, and lung) were tested by four different
      assays, including iron chelation, 2,2'-azino-bis (3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS) radical scavenging, 2,2-Diphenyl-1-(2,4,6-trinitrophenyl)
      hydrazyl (DPPH) radical scavenging, and inhibition of lipid oxidation. All
      hydrolyzed tissues displayed antioxidant capacity in all four assays, with colon,
      liver, and appendix as the three most potent inhibitors of lipid oxidation (47,
      29, and 27 mmol/L trolox equivalent antioxidant capacity [TEAC], respectively)
      and liver, colon, pancreas, and appendix as the four most potent iron chelators
      (92% +/- 1.1, 79.3% +/- 3.2, 77.1% +/- 1.8, and 77% +/- 2.3, respectively).
      Furthermore, colon and appendix showed good radical scavenging capacities with
      ABTS scavenging of 86.4% +/- 2.1 and 84.4% +/- 2.9 and DPPH scavenging of 17.6%
      +/- 0.3 and 17.1% +/- 0.2, respectively. Our results provide new knowledge about
      the antioxidant capacity of a variety of animal by-products, which can be
      transformed into antioxidant hydrolysates, thereby creating added value. 

PMID- 24936299
TI  - The content of soyasaponin and soyasapogenol in soy foods and their estimated
      intake in the Japanese.
AB  - Soyasaponins have been reported to promote various health functions. However, the
      total soyasaponin and soyasapogenol content in soy products and the daily intake
      remain to be fully elucidated. We developed a high-performance liquid
      chromatography coupled with tandem mass spectrometric (HPLC-MS/MS) method to
      evaluate the content of group A and B soyasaponins and soyasapogenols. The total
      soyasaponin content was measured after pretreatment converted soyasaponins to
      soyasapogenols. The total soyasaponin content in soy foods was 200-1800 nmol g(
      1), although that of soy sauce was 2-7 nmol g(-1). The soyasapogenol to total
      soyasaponin ratio was 30-50% in long-term matured miso. The majority of the
      soyasapogenol detected was soyasapogenol B rather than soyasapogenol A, resulting
      in speculation that further steps are required to liberate aglycones from
      glycoside-conjugated soyasaponins in soyasapogenol A. We estimated the daily
      intake of total soyasaponins and soyasapogenols by the Japanese, which was 50.3
      and 0.59 MUmol, respectively. The soyasapogenol content and the soyasapogenol to
      total soyasaponin ratio was considerably low in most soy products, except for
      long-term maturated miso. The major source of the daily intake of soyasaponins
      and soyasapogenols were tofu and miso, respectively. 

PMID- 24936302
TI  - Does zafirlukast reduce future risk of asthma exacerbations in adults? Systematic
      review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The purpose of asthma management is to achieve a total
      asthma control that involves current control and future risk. It has proven
      efficacy in reducing asthma exacerbations, but the effect size of zafirlukast for
      asthma exacerbations of various severity is not systematically explored. METHODS:
      Randomized controlled trials were searched in PubMed Central, Web of Science, and
      Embase, where zafirlukast prevented asthma exacerbations in adults. The primary
      outcome was asthma exacerbations, the secondary outcomes were asthma
      exacerbations requiring systemic corticosteroids and emergency visits,
      respectively. Odds ratio (OR) with 95% confidence intervals (CI) were pooled.
      RESULTS: Twelve trials were identified. As first-line therapy, compared to those
      having placebo, the patients with chronic asthma receiving zafirlukast
      experienced statistically lower asthma exacerbations (OR = 0.68, 95% CI = [0.45,
      1.00]), but it was not found that zafirlukast was superior to placebo in asthma
      exacerbations requiring systemic corticosteroids (OR = 0.76, 95% CI = [0.45,
      1.29]). Furthermore, zafirlukast was inferior to ICs in asthma exacerbations (OR
      = 2.11, 95% CI = [1.35, 3.30]) and requiring systemic corticosteroids (OR = 3.71,
      95% CI = [1.82, 7.59]). As add-on therapy, zafirlukast was not superior to
      placebo in asthma exacerbations (OR =0.99, 95% CI = [0.54, 1.81] and requiring
      emergency visits (OR = 0.72, 95% CI = [0.18, 2.99]). Intriguingly, there was not
      a significant difference in asthma exacerbations between zafirlukast and ICs (OR
      = 1.12, 95% CI = [0.53, 2.34]). CONCLUSIONS: Our study suggests that zafirlukast,
      as the first-line therapy, significantly reduces mild to moderate but not severe
      asthma exacerbations. In the add-on regimen, zafirlukast could not reduce asthma
      exacerbations, which would perhaps result from small sample size and needs to be
      further studied.

PMID- 24936303
TI  - Look at the lung: can chest ultrasonography be useful in pregnancy?
AB  - BACKGROUND: This study aimed to evaluate the clinical value of chest ultrasound
      (US) in the detection, diagnosis and follow-up of pathologic processes of both
      peripheral lung parenchyma and pleural space in pregnant women. FINDINGS:
      Pregnant women admitted to Obstetric Pathology Hospital Department for
      respiratory diseases were enrolled. Chest US examination was performed when there
      was a respiratory disease highly suggestive of pneumonia and/or pleural effusion
      and chest X-ray (CXR) should have been obtained. Three chest US patterns were
      identified: lung consolidation (LC), pleural effusion (PE) and focal sonographic
      interstitial syndromes (SIS). When chest US pathologic signs were reported, one
      or more subsequent chest US examinations were performed to follow-up the patient
      until their complete resolution. Sixteen inpatients underwent 54 chest US
      evaluations. We identified: 9 LCs, 6 PEs and 11 SISs. Total number of CXRs was 7
      (10 females avoided X-rays exposure and one underwent 2 CXR evaluations on the
      advice of Gynecologist). Chest US follow-up, during and after therapy, showed
      complete resolution of echographic patterns previously described. CONCLUSIONS:
      Chest US evaluation during pregnancy is a useful diagnostic tool to detect and
      monitor respiratory diseases, avoiding excessive X-rays exposure.

PMID- 24936304
TI  - Short-term sensory and cutaneous vascular responses to therapeutic ultrasound in
      the forearms of healthy volunteers.
AB  - BACKGROUND: Therapeutic ultrasound (US) is used for a variety of clinical
      pathologies and is thought to accelerate tissue repair and help with pain
      reduction via its thermal and nonthermal effects. The evidence on physiological
      effects of US on both sensory and vascular functions in humans is incomplete.
      Hence, the purpose of this study was to determine the short-term impact of two
      doses of US (3 MHz, 1:4, 0.25 W/cm(2), 5 min; 1 MHz, continuous, 0.8 W/cm(2), 3
      min), on sensory and vascular responses in the healthy forearms. METHODS: Twenty
      healthy subjects were recruited (mean age, 29.6 +/- 8.8 years) for the study.
      Superficial blood flow (SBF) in the distal forearms was determined using the
      tissue viability imaging system. Sensory perception thresholds (SPT) were
      determined from ring finger (C7, C8) to assess A-beta (at 2,000 Hz) and C fiber
      function (at 5 Hz), using a Neurometer CPT/C device. Subject's two hands were
      randomly allocated to group order (AB/BA). Scores were obtained before and
      immediately after the application of US and control. Differences in these were
      analyzed using repeated measures. RESULTS: Both 3 MHz pulsed US and 1 MHz
      continuous US showed small to moderate (effect size = 0.12 to 0.68),
      statistically significant reductions in SBF (3 MHz, mean change = 2.8 AU and 1
      MHz, mean change = 3.9 AU, p < 0.05 respectively), skin temperature (2.5 degrees
      C and 1.1 degrees C, p < 0.05), and SPT at 5 Hz (1.3 and 1 mA, p < 0.05) across
      time. SPT at 2,000 Hz remained unaltered by all three conditions (p > 0.05). Age
      and gender also had no effect on all outcome measures (p > 0.05). CONCLUSION:
      This study demonstrated minor reductions in skin blood flow, skin temperatures,
      and C fiber perception thresholds immediately after 3 MHz, and 1 MHz US. The
      responses observed may have been due to a thermo-cooling effect of the gel or due
      to the direct effect of US on C fibers of median and ulnar nerves. US had a
      negligible effect on A-beta fibres. This would suggest that future studies
      looking at physiological effects of US should move towards investigating larger
      dosages and study the effects in patient populations.

PMID- 24936305
TI  - Removal of tetracycline from wastewater using pumice stone: equilibrium, kinetic
      and thermodynamic studies.
AB  - In this study, pumice stone was used for the removal of tetracyline (TC) from
      aqueous solutions. It was characterized by XRD, FT-IR, SEM and BET analyses.
      Cation exchange capacity of pumice stone was found to be 9.9 meq/100 g. Effect of
      various parameters such as solution pH (2-11), adsorbent dosage (0.5-10 g/L),
      contact time (2.5-120 min), initial TC concentration (5-300 mg/L) and temperature
      (20-50 degrees C) on TC adsorption onto pumice was investigated. Also the
      adsorption of TC on pumice stone was studied as a function of Na(+) and Cu(2+)
      cations changing pH from 2 to 11 using batch experiments. The best removal
      efficiency performance was exhibited at adsorbent dosage 10 g/L, pH 3, contact
      time 120 min. Langmuir, Freundlich and Dubinin-Radushkevich (D-R) isotherm models
      were applied to the equilibrium data. The result has shown that the adsorption
      was favorable, physicochemical in nature and agrees well with Langmuir and
      Freundlich models. The maximum Langmuir adsorption capacity was found to be 20.02
      mg/g. The adsorption behavior of TC on pumices stone was fitted well in the
      pseudo-second order kinetics model. Thermodynamic parameters calculated from the
      adsorption data at different temperature showed that the adsorption reaction was
      feasible, spontaneous and exothermic. 

PMID- 24936306
TI  - Radiation sterilization of new drug delivery systems.
AB  - Radiation sterilization has now become a commonly used method for sterilization
      of several active ingredients in drugs or drug delivery systems containing these
      substances. In this context, many applications have been performed on the human
      products that are required to be sterile, as well as on pharmaceutical products
      prepared to be developed. The new drug delivery systems designed to deliver the
      medication to the target tissue or organ, such as microspheres, nanospheres,
      microemulsion, and liposomal systems, have been sterilized by gamma (gamma) and
      beta (beta) rays, and more recently, by e-beam sterilization. In this review, the
      sterilization of new drug delivery systems was discussed other than conventional
      drug delivery systems by gamma irradiation. 

PMID- 24936307
TI  - Measurement of flow diverter hydraulic resistance to model flow modification in
      and around intracranial aneurysms.
AB  - Flow diverters (FDs) have been successfully applied in the recent decade to the
      treatment of intracranial aneurysms by impairing the communication between the
      flows in the parent artery and the aneurysm and, thus, the blood within the
      aneurysm sac. It would be desirable to have a simple and accurate computational
      method to follow the changes in the peri- and intraaneurysmal flow caused by the
      presence of FDs. The detailed flow simulation around the intricate wire structure
      of the FDs has three disadvantages: need for high amount of computational
      resources and highly skilled professionals to prepare the computational grid, and
      also the lack of validation that makes the invested effort questionable. In this
      paper, we propose a porous layer method to model the hydraulic resistance (HR) of
      one or several layers of the FDs. The basis of this proposal is twofold: first,
      from an application point of view, the only interesting parameter regarding the
      function of the FD is its HR; second, we have developed a method to measure the
      HR with a simple apparatus. We present the results of these measurements and
      demonstrate their utility in numerical simulations of patient-specific aneurysm
      simulations. 

PMID- 24936308
TI  - Current practice and perspective of hands-free defibrillation in Hungary -
      Investigating the obstacles of implementation.
AB  - Defibrillation with self-adhesive pads is the gold standard method during
      resuscitation as it allows minimal interruptions of chest compressions.
      Unfortunately, the implementation of the new recommendations often requires the
      purchase of new equipment. We have conducted a nationwide survey by telephone
      interviews with senior clinicians in order to investigate the current position of
      the implementation and to identify possible obstacles. We have audited 56
      hospitals and 92 departments across the country and interviewed the senior
      consultants of the intensive care units (ICUs) and emergency departments (EDs).
      Only 6.5% of all responders were using hands-free defibrillation routinely at the
      time of the survey. According to 67.4% of respondents, purchasing of new
      equipment was not likely within 2 years. The major obstacle was the perceived
      higher costs (59.8%); however, the majority of clinicians (92.4%) were aware of
      the potential benefits of hands-free defibrillation. Our results suggest that the
      implementation of the new guidelines is slower than expected due to the
      unavailability of hands-free defibrillators. The major obstacle is the perceived
      cost-efficiency concerns. The need for an interim recommendation for safe
      delivery of defibrillation using hard paddles might be considered to enhance the
      chance of survival for a large number of patients. 

PMID- 24936309
TI  - Pulmonary function derangements in isolated or predominant mitral stenosis -
      Preoperative evaluation with clinico-hemodynamic correlation.
AB  - INTRODUCTION: It is well known that mitral stenosis (MS) is complicated by
      pulmonary hypertension (PH) of varying degrees. The hemodynamic derangement is
      associated with structural changes in the pulmonary vessels and parenchyma and
      also functional derangements. This article analyzes the pulmonary function
      derangements in 25 patients with isolated/predominant mitral stenosis of varying
      severity. AIMS: THE AIM OF THE STUDY WAS TO CORRELATE THE PULMONARY FUNCTION TEST
      (PFT) DERANGEMENTS (DONE BY SIMPLE METHODS) WITH: a) patient demographics and
      clinical profile, b) severity of the mitral stenosis, and c) severity of
      pulmonary artery hypertension (PAH) and d) to evaluate its significance in
      preoperative assessment. SUBJECTS AND METHODS: This cross-sectional study was
      conducted in 25 patients with mitral stenosis who were selected for mitral valve
      (MV) surgery. The patients were evaluated for clinical class, echocardiographic
      severity of mitral stenosis and pulmonary hypertension, and with simple methods
      of assessment of pulmonary function with spirometry and blood gas analysis. The
      diagnosis and classification were made on standardized criteria. The associations
      and correlations of parameters, and the difference in groups of severity were
      analyzed statistically with Statistical Package for Social Sciences (SPSS), using
      nonparametric measures. RESULTS: THE SPIROMETRIC PARAMETERS SHOWED SIGNIFICANT
      CORRELATION WITH INCREASING NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL CLASS
      (FC): forced vital capacity (FVC, r = -0.4*, p = 0.04), forced expiratory volume
      in one second (FEV1, r = -0.5*, p = 0.01), FEV1/FVC (r = -0.44*, p = 0.02), and
      with pulmonary venous congestion (PVC): FVC (r = -0.41*, p = 0.04) and FEV1 (r = 
      0.41*, p = 0.04). Cardiothoracic ratio (CTR) correlated only with FEV1 (r = 
      0.461*, p = 0.02) and peripheral saturation of oxygen (SPO2, r = -0.401*, p =
      0.04). There was no linear correlation to duration of symptoms, mitral valve
      orifice area, or pulmonary hypertension, except for MV gradient with PCO2 (r =
      0.594**, p = 0.002). The decreased oxygenation status correlated significantly
      with FC, CTR, PVC, and with deranged spirometry (r = 0.495*, p = 0.02).
      CONCLUSIONS: PFT derangements are seen in all grades of severity of MS and
      correlate well with the functional class, though no significant linear
      correlation with grades of severity of stenosis or pulmonary hypertension. Even
      the early or mild derangements in pulmonary function such as small airway
      obstruction in the less severe cases of normal or mild PH can be detected by
      simple and inexpensive methods when the conventional parameters are normal. The
      supplementary data from baseline arterial blood gas analysis is informative and
      relevant. This reclassified pulmonary function status might be prognostically
      predictive.

PMID- 24936310
TI  - Successful reimplantation of the hypertrophied inferior mesenteric artery during
      an open abdominal aortic aneurysm repair.
AB  - Ischemic colitis is the most common form of an iatrogenic intestinal ischemia
      following an aortic surgery. It can be transient and self-limiting but, when
      severe, is associated with mortality even as high as 80%. Careful preoperative
      assessment can help to anticipate the need for the inferior mesenteric artery
      (IMA) reimplantation. Some patients lack the sufficient collateral blood supply
      to the colon and can benefit from the IMA reimplantation, which not only reduces
      the risk of postoperative colonic necrosis but also can be lifesaving. We report
      a case of a successful reimplantation of the IMA based on the careful
      preoperative planning. If unrecognized, this undoubtedly would lead to
      postoperative colonic ischemia. Therefore, we feel it is important to share our
      experience regarding the successful management of the presented case. 

PMID- 24936311
TI  - Successful thrombolysis using recombinant tissue plasminogen activator in cases
      of severe pulmonary embolism with mobile thrombi in the right atrium.
AB  - Hereby, we report two cases of acute pulmonary embolism with concomitant right
      sided thrombus, which were successfully treated using recombinant tissue
      plasminogen activator (rtPA). These patients had life-threatening acute right
      ventricular failure, which dramatically improved within hours following
      thrombolysis. These cases emphasize the clinical utility of rtPA for the
      treatment of life-threatening pulmonary embolism. 

PMID- 24936312
TI  - Retrieval of embolized tip of port catheter from branch of right pulmonary artery
      using a macro snare catheter.
AB  - Rupture of the silicon port catheter is a relatively rare complication. Ruptured
      part usually embolizes; therefore, removal of foreign body may be difficult.
      These ports usually migrate to right-sided chambers, main pulmonary arteries, and
      pulmonary subbranches. Different devices such as snares, basket catheters, and
      ablation catheters are utilized for retrieval. Hereby, we report successful
      extraction of an embolized 10-cm tip of a vascular access port using a macro
      snare catheter. 

PMID- 24936314
TI  - Europe and ESTRO moving East. A story of betrayal and redemption-Candid
      observations by a privileged witness.
AB  - After briefly looking into the dramatic twist of history that caused Central- and
      Eastern Europe to be separated from the West, the author observes the impact of
      40 years of cold war and isolation on the state of radiotherapy (RT) in Central
      Europe. From her privileged position as a staff member in charge of public
      relations and society development at the European Society for Therapeutic
      Radiology and Oncology (ESTRO), she witnesses and helps drive the "rapprochement"
      between radiation oncology professionals from both sides of the former iron
      curtain. Thanks to substantial support from target tailored EU projects, ESTRO
      was in a position to give a powerful impulse to the re-integration of Central
      European RT in the mainstream of European health care. The author describes from
      her own and privileged perspective the excitement of discovering the rich
      heritage of a shared common past and expresses her concern that in the dynamic
      repositioning of Europe's point of gravity towards the East, the multiple but
      still fragile links between Central- and West European radiotherapy, tied within
      ESTRO, should not get dissolved in transition. 

PMID- 24936313
TI  - Opportunities for rehabilitation of patients with radiation fibrosis syndrome.
AB  - This review discusses the pathophysiology, evaluation, and treatment of
      neuromuscular, musculoskeletal, and functional disorders that can result as late
      effects of radiation treatment. Although radiation therapy is often an effective
      method of killing cancer cells, it can also damage nearby blood vessels that
      nourish the skin, ligaments, tendons, muscles, nerves, bones and lungs. This can
      result in a progressive condition called radiation fibrosis syndrome (RFS). It is
      generally a late complication of radiotherapy which may manifest clinically years
      after treatment. Radiation-induced damage can include "myelo-radiculo-plexo-neuro
      myopathy," causing muscle weakness and dysfunction and contributing to
      neuromuscular injury. RFS is a serious and lifelong disorder which, nevertheless,
      may often be decremented when identified and rehabilitated early enough. This
      medical treatment should be a complex procedure consisting of education, physical
      therapy, occupational therapy, orthotics as well as medications. 

PMID- 24936315
TI  - Wax boluses and accuracy of EBT and RTQA radiochromic film detectors in
      radiotherapy with the JINR Phasotron proton beam.
AB  - AIM: To present the results obtained using radiochromic films EBT and RTQA 1010P
      for the reconstruction the dose distributions for targets irradiated by proton
      beam and modified by wax boluses. BACKGROUND: In Medico-Technical Complex at the
      Joint Institute for Nuclear Research in Dubna implemented technology of wax
      boluses. MATERIALS AND METHODS: Wax boluses are easier to make and they give
      better dose distributions than boluses made from modeling clay previously used at
      our center. We irradiated two imaginary targets, one shaped as a cylinder and the
      other one as two cuboids. The evaluated calibration curve was used for
      calculation of the dose distributions measured by the EBT and RTQA radiochromic
      film. In both cases, the measured dose distributions were compared to the dose
      distributions calculated by the treatment planning system (TPS). We also compared
      dose distributions using three different conformity indices at a 95% isodose.
      RESULTS: Better target coverage and better compliance of measurements
      (semiconductor detectors and radiochromic films) with calculated doses was
      obtained for cylindrical target than for cuboidal target. The 95% isodose covered
      well the tumor for both target shapes, while for cuboidal target larger volume
      around the target received therapeutic dose, due to the complicated target shape.
      The use wax boluses provided to be effective tool in modifying proton beam to
      achieve appropriate shape of isodose distribution. CONCLUSION: EBT film yielded
      the best visual matching. Both EBT and RTQA films confirmed good conformity
      between calculated and measured doses, thus confirming that wax boluses used to
      modify the proton beam resulted in good dose distributions.

PMID- 24936316
TI  - Evaluation of results of linac-based radiosurgery for brain metastases from
      primary lung cancer.
AB  - AIM: The purpose of our review was to evaluate results of radiosurgery for
      patients with brain metastases from lung cancer. BACKGROUND: Lung cancer is the
      leading cause of death from cancer and the most common source of brain
      metastases. Radiosurgery allows the precise focal delivery of a high single
      radiation dose to brain metastases and results in high rates of local control.
      MATERIALS AND METHODS: 83 patients were treated between 2006 and 2008. We
      evaluated local control and outcome after radiosurgery and identified prognostic
      factors. RESULTS: Median survival in the whole group was 7.8 months from
      radiosurgery and 11 months from diagnosis. Median survival in classes I, II and
      III was 13.2, 8.2 and 2.2 months. For 94% of patients symptoms improved or
      stabilised at the first follow-up visit and this status did not change during 7.1
      months. According to the univariate analysis, factors associated with improved
      survival included: RPA class 1 compared with RPA 2 and 3, RPA class 2 compared
      with RPA 3, KPS > 70, control of the primary disease, radiosurgery performed more
      than once, level of haemoglobin >7 mmol/1, absence of extracranial metastases,
      volume of the biggest lesion <11 cm(3). The multivariate analysis confirmed a
      significant influence on survival for the following factors: RPA class 1 as
      compared with RPA 3, KPS > 70, absence of extracranial metastases, multiplicity
      of radiosurgery. CONCLUSIONS: Stereotactic radiosurgery is a safe and effective
      treatment. It proved to be effective and safe in older patients. Selection of
      patients who are likely to benefit most should be based on prognostic factors.
      KPS proved to be the most important prognostic factor. In the RPA III group
      (patients with KPS < 70) survival time was similar to that achieved after
      symptomatic medical management.

PMID- 24936317
TI  - Monte Carlo characterizations mapping of the (gamma,n) and (n,gamma) photonuclear
      reactions in the high energy X-ray radiation therapy.
AB  - AIM: The aim of this work was to map the characteristics of (n,gamma) and
      (gamma,n) reactions in a high energy photon radiation therapy. BACKGROUND:
      Photoneutrons produced in the high energy X-Ray radiation therapy may damage
      patients and staff. It is due to high RBE of the produced neutrons according to
      their energy and isotropic emission. Characterization of the photoneutrons can
      help us in appropriate shielding. MATERIALS AND METHODS: This study focused on
      the photoneutron and capture gamma ray phenomena. Characteristics such as dose
      value, fluence and spectra of both the neutrons and the by produced prompt gamma
      ray were described. RESULTS AND DISCUSSION: Neutron and prompt gamma spectra in
      different points showed the neutrons to be thermalized when increasing the
      distance from the linac. Energy of the neutrons changed from about 0.6 MeV at the
      isocentre to around 10(-08) MeV at the outer door position. Although the neutrons
      were found as fast neutrons, their spectra showed they were thermal neutrons at
      the outer door position. Additionally, it was seen that the energy of the gamma
      rays is higher than the scattered X-ray energy. The energy of gamma rays was seen
      to be up to 10 MeV while the linac photons had energy lower than 1 MeV. Neutron
      source strength obtained in this work was in good agreement with the published
      data, which may be a confirmation of our simulation accuracy. CONCLUSION: The
      study showed that the Monte Carlo simulation can be applied in the radiotherapy
      and industrial radiation works as a useful and precise estimator. We also
      concluded that the dose from the prompt gamma ray at the outer door location is
      higher than the scattered radiation from the linac and should be considered in
      the shielding.

PMID- 24936319
TI  - Biological effects and equivalent doses in radiotherapy: A software solution.
AB  - BACKGROUND: The limits of TDF (time, dose, and fractionation) and linear
      quadratic models have been known for a long time. Medical physicists and
      physicians are required to provide fast and reliable interpretations regarding
      delivered doses or any future prescriptions relating to treatment changes. AIM:
      We, therefore, propose a calculation interface under the GNU license to be used
      for equivalent doses, biological doses, and normal tumor complication probability
      (Lyman model). MATERIALS AND METHODS: THE METHODOLOGY USED DRAWS FROM SEVERAL
      SOURCES: the linear-quadratic-linear model of Astrahan, the repopulation effects
      of Dale, and the prediction of multi-fractionated treatments of Thames. RESULTS
      AND CONCLUSIONS: The results are obtained from an algorithm that minimizes an ad
      hoc cost function, and then compared to an equivalent dose computed using
      standard calculators in seven French radiotherapy centers.

PMID- 24936318
TI  - Clinical management of secondary angiosarcoma after breast conservation therapy.
AB  - AIM: The aim of this paper is to summarize the treatment outputs of secondary
      angiosarcoma after breast conservation therapy at St. Eizabeth Cancer Centre,
      Slovakia. BACKGROUND: Angiosarcoma of the breast is a rare but very aggressive
      malignant tumor of the vascular endothelium, characterized by rapidly
      proliferating and extensively infiltrating growth. Breast angiosarcoma may occur
      de novo, or as a complication of radiation therapy, or chronic lymphedema
      secondary to axillary lymph node dissection for mammary carcinoma. Radiotherapy
      in the treatment of breast cancer is associated with an increased risk of
      subsequent sarcoma. MATERIALS AND METHODS: Retrospective study of medical records
      from the cancer databases was done in order to analyze the secondary breast
      angiosarcoma. This disease is an iatrogenic condition that warrants close follow
      up and judicial use of radiotherapy in breast conserving therapy. Therefore, it
      is more prevalent in cases treated with radiotherapy, occurring especially in or
      adjacent to the radiation field. Clinical histories and follow-up data of
      identified patients after breast conservation therapy of invasive breast cancer
      were reviewed. In addition, a comprehensive literature review on diagnosis and
      treatment procedures was done in order to summarize state-of-the-art clinical
      approach. RESULTS AND DISCUSSIONS: Three cases of secondary angiosarcoma after
      breast conservation therapy (BCT) were identified among 4600 patients treated at
      St. Elizabeth Cancer Institute during previous 16 years (1995-2011). Secondary
      breast angiosarcoma was diagnosed in a median period of 11 years following
      primary radiotherapy, median age at the time of diagnosis was 75 years. Surgical
      treatment consisted of radical mastectomy. The first patient, a 56-year-old woman
      received neoadjuvant chemotherapy (docetaxel + gemcitabin), second one (75 year)
      was treated by radiotherapy (TD 26 Gy, 2 Gy per fraction), since chemotherapy was
      not indicated. The last patient (80 year) got adjuvant chemotherapy (paclitaxel).
      Average follow up of the patients was 31 months. As of 31 July 2012, our patients
      were doing well without evidence of recurrent disease after treatment.
      CONCLUSIONS: Angiosarcoma remains a difficult management problem with poor loco
      regional and distal control. In our study, an overall incidence rate of secondary
      breast angiosarcoma is 0.065%. Although the prognosis for this disease is poor
      (typical survival period is 14.5-34 months with a 5-year survival rate of
      approximately 15%), all the three patients treated at our institute are alive and
      disease-free at the end of reported period. Finally, it is assumed that the use
      of breast conserving therapy will increase the incidence of post-irradiation
      angiosarcoma but the small difference in risk of subsequent sarcoma of the breast
      cancer patients receiving radiotherapy does not suppress its benefit.

PMID- 24936320
TI  - Tolerance of the vaginal vault to high-dose rate brachytherapy and concomitant
      chemo-pelvic irradiation: Long-term perspective.
AB  - AIM/BACKGROUND: We sought to determine the tolerance level and complication rates
      of the vaginal vault to combined high-dose-rate intra-cavitary brachytherapy with
      concomitant chemo-radiotherapy. PATIENTS AND METHODS: A retrospective review of
      medical records of all the patients who received definitive chemo-radiotherapy
      for cervical cancer between 1998 and 2002 was undertaken. The records were
      reviewed for doses and for radiation-associated early and late sequelae of the
      vagina, rectum and bladder. Cumulative biological effective dose was calculated
      for two reference vaginal surface points. RESULTS: Fifty patients were included.
      Average age at diagnosis was 54 years. Median follow-up was 59 months. There were
      no recorded instances of acute grade IV toxicity. Maximal high-dose-rate vaginal
      surface dose (upper central point) was 103 Gy, and maximal brachytherapy lateral
      surface dose was 70 Gy. Maximal cumulative biological effective dose for the
      lateral surface reference point was 465.5 Gy3, and the maximal cumulative
      biological effective dose for the superior reference point was 878.6 Gy3. There
      were no cases of vaginal necrosis or fistulas, and no cases of grade IV late
      vaginal, rectal or bladder toxicity. No correlation was found between the maximal
      vaginal surface dose and vaginal, rectal or bladder toxicity. CONCLUSIONS: The
      maximal surface HDR brachytherapy dose of 103 Gy and the maximal cBED of 878.6
      Gy3 were not associated with fistula or necrosis or other grade 3-4 vaginal
      complications. Concomitant chemo-radiotherapy, including pelvic radiotherapy and
      high-dose-rate intracavitary brachytherapy, is relatively safe for cervical
      cancer patients.

PMID- 24936321
TI  - Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder.
AB  - BACKGROUND: Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non
      small cell lung cancer. There is no consensus regarding optimal management for
      this disease. CASE REPORT: We present a case of MEC of the lung in a 75 year-old
      female with a history of superficial urothelial carcinoma of the bladder. The
      patient was found to have an asymptomatic lung mass. Initial biopsy suggested
      metastatic recurrence of urothelial carcinoma and therefore, cisplatin and
      gemcitabine chemotherapy was administered prior to surgical resection.
      Pathological analysis of the resected specimen confirmed a diagnosis of stage
      IIIA MEC with focal high-grade features including transitional cell-like areas.
      Adjuvant radiotherapy was administered due to a positive microscopic resection
      margin. No chemotherapy was given due to lack of supporting data. The patient
      developed widespread metastatic disease 3 months following completion of
      radiotherapy and died 1 month later. CONCLUSION: This case demonstrates the
      possibility of dual pathology in cases where metastatic disease is suspected. The
      use of small tissue samples may complicate diagnosis due to the heterogeneity of
      malignant tumours.

PMID- 24936322
TI  - Breast cancer local recurrence under the form of inflammatory carcinoma, treated
      with concurrent radiation and chemotherapy, a case report.
AB  - The authors present a case report of a patient with breast cancer diagnosed in
      2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy,
      followed by hormonal therapy until 2010, who relapsed under the form of
      inflammatory breast cancer in 2011. After tumor progression detected during
      primary systemic therapy, a concurrent radiation and radiosensitizing
      chemotherapy were proposed. There was a significant clinical response to this
      treatment, enabling curative chance with total mastectomy. The histological
      examination of the breast and regional lymph nodes revealed a complete response,
      since there was no evidence of residual tumor. There are few reports concerning
      concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but
      it could be a suitable "loco regional rescue therapy" to further reduce tumor
      progression and allow curative surgery. Study of this treatment strategy in
      randomized clinical trials is warranted. 

PMID- 24936323
TI  - Total skin electron irradiation-The technique where the electron beams are still
      irreplaceable.

PMID- 24936324
TI  - Diagnostics in mycosis fungoides and Sezary syndrome.
AB  - AIM: The aim of this paper was to present diagnostic methods helping in the
      recognition of mycosis fungoides (MF) and Sezary syndrome (SS). BACKGROUND:
      Mycosis fungoides is the most common form of primary cutaneous T-cell lymphomas.
      It is characterized by a distinctive long-term course and malignant T-cell
      proliferation. MF diagnosis is not easy, mainly due to the atypical clinical
      presentation of the disease at an early stage. MATERIALS AND METHODS: Low
      specific changes, which can be observed at the histopathological examination.
      Initially, the skin lesions may resemble psoriasis, atopic dermatitis or chronic
      eczema. Patients are qualified according to the available, and generally accepted
      WHO-EORTC classification, based on a combination of clinical and
      histopathological markers. From a clinical point of view, it is also important to
      carry out the qualification according to the TNMB assessment, which allows to
      specify the stage of the disease, and is helpful in the monitoring of the course
      of disease and therapeutic effects. RESULTS: In this paper we try to present
      currently available diagnostic methods. CONCLUSION: Diagnosis of MF and SS still
      causes many problems due to less characteristic changes in the early stage of
      disease and requires wide interdisciplinary knowledge.

PMID- 24936326
TI  - Literature review of clinical results of total skin electron irradiation (TSEBT)
      of mycosis fungoides in adults.
AB  - BACKGROUND: Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin
      lymphoma of T cell origin. Even with the establishment of MF staging, the initial
      treatment strategy often remains unclear. AIM: The aim of this study was to
      review the clinical results of total skin electron beam therapy (TSEBT) for MF in
      adults published in English language scientific journals searched in
      Pubmed/Medline database until December 2012. RESULTS: MF is very sensitive to
      radiation therapy (RT) delivered either by photons or by electrons. In limited
      patches and/or plaques local electron beam irradiation results in good outcomes
      besides the fact of not being superior to other modalities. For extensive patches
      and/or plaques data suggest that TSEBT shows superior response rates. The
      cutaneous disease presentation is favorably managed with radiotherapy due to its
      ability to treat the full thickness of deeply infiltrated skin. For generalized
      erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For
      advanced disease, palliation, or recurrence after the first radiotherapy
      treatment course, TSEBT may still be beneficial, with acceptable toxicity.
      Recommended dose is 30-36 Gy delivered in 6-10 weeks. CONCLUSION: TSEBT can be
      used to treat any stage of MF. It also presents good tumor response with symptoms
      of relief and a palliative effect on MF, either after previous irradiation or
      failure of other treatment strategies.

PMID- 24936325
TI  - The current management of mycosis fungoides and Sezary syndrome and the role of
      radiotherapy: Principles and indications.
AB  - AIM: To evaluate the current treatment of mycosis fungoides (MF) and Sezary
      syndrome (SS) focusing on the role of radiotherapy (RT), its principles and
      indications, and the perspectives of the novel irradiation technologies.
      BACKGROUND: MF and SS are rare lymphoproliferative diseases whose incidence is
      increasing. For a long time RT has been used as a single modality or in
      integrated treatment programs for these diseases. MATERIALS AND METHODS: The
      latest systematic reviews, primary studies and new diagnostic and treatment
      guidelines on MF and SS were analyzed. Clinical outcomes together with the
      technical aspects and the role of RT were also evaluated. RESULTS: New data are
      available on pathogenesis, diagnostic criteria, classification and staging
      procedures for MF and SS and several local and systemic therapies are proposed.
      Localized RT can cure "minimal stage" MF while total skin electron beam
      irradiation (TSEI) may cure initial-stage disease and may offer important symptom
      relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT
      is not largely used, mainly because of some technical difficulties but new RT
      technologies may be proposed to treat large skin surfaces. CONCLUSIONS: New
      treatment programs offer good results, with median survival of more than 12 years
      in early-stage MF, but the median survival of 2.5 years or less in advanced
      stages is still a challenge. RT remains an option for all stages with a good
      cost/effectiveness ratio in a curative or palliative setting. New RT technologies
      can overcome some technical problems of treating large skin surfaces.

PMID- 24936327
TI  - Clinical results of the total skin electron irradiation of the mycosis fungoides
      in adults. Conventional fractionation and low dose schemes.
AB  - BACKGROUND: Mycosis fungoides (MF) is a rare skin condition, effectively treated
      by irradiation. Since 1951, different methods of total skin irradiation have been
      developed. Although dose-response effect has been demonstrated in many
      publications, controversies about low dose treatment still exist. AIM: The
      analysis of results of the total skin electron irradiation (TSEI), especially low
      dose TSEI in comparison with standard dose treatment is the subject of this
      review. Also, acute and late side effects of radiotherapy in MF are discussed.
      MATERIALS AND METHODS: Medline search and analysis of studies published between
      1995 and 2012, containing key words: mycosis fungoides, standard dose TSEI, low
      dose TSEI, total skin electron beam therapy (TSEBT). RESULTS: Detailed analysis
      of relevant studies demonstrated that standard dose radiotherapy 30-36 Gy is the
      most effective treatment used in clinical practice. Objective response rate (ORR)
      is high, especially for less advanced stages of disease. Complete response rate
      (CR), although slightly lower, is still relatively high. For more advanced MF,
      TSEI serves as a very good method of palliative treatment and relief of symptoms,
      like pruritus, pain or desquamation. There is no consensus regarding low dose
      TSEI; the method is widely accepted as a palliative treatment or in case of
      reirradiation. CONCLUSIONS: Standard dose TSEI is an effective method of MF
      treatment for radical and palliative treatment, producing high rate of ORR and
      reasonably long time to progression (TTP). Acute and late side effect of
      treatment are mostly mild and easy to manage. Low dose TSEI is still in the phase
      of clinical studies.

PMID- 24936329
TI  - Total skin electron beam (TSEB) therapy in pediatric patients: A review of the
      literature.
AB  - AIM: A literature review was undertaken to identify current TSEB therapy in
      pediatric patients. BACKGROUND: Total skin electron beam (TSEB) therapy is a
      method of irradiation with low energy electron beam dedicated to patients who
      have superficial skin lesions all over their body. Such skin malignancies are
      sparse among adults and even more uncommon with pediatric population. MATERIALS
      AND METHODS: In this study, all reported case reports were summed up with a
      special emphasis on techniques used, doses prescribed and special shielding of
      critical organs. Moreover, potential problems that were encountered during TSEB
      irradiation of very young patients were depicted. RESULTS: The literature has
      described only seven case reports of children undergoing TSEB therapy. Most of
      them were infants; however, two adolescents were also treated. For all infants,
      general anesthesia was provided to allow safe and accurate TSEB irradiation. The
      prescribed dose varied from 16 Gy to 28 Gy depending on the irradiation schedule
      and patient condition. Usually, boost fields were applied to the scalp and
      perineum. Typical shields for fingernails, toenails and lenses were usually used.
      CONCLUSION: This paper revealed that TSEB therapy may be considered as a
      palliative treatment for pediatric patients with leukemia cutis. However, its
      role is still unclear and should be further investigated.

PMID- 24936328
TI  - Advantages and implications of high dose rate (HDR) total skin electron
      irradiation (TSEI) for the management of Mycosis Fungoides. Indian experience.
AB  - BACKGROUND: Mycosis Fungoides (MF) is an indolent lymphoproliferative disorder
      affecting dermis caused by abnormal proliferation of CD4+ T-cells. Radiation
      therapy is the most effective modality of treatment for MF which offers cure in
      limited stage disease and desirable palliation in advance stage disease. Treating
      entire skin having many curved surfaces and folds with radiation is the real
      challenge for the radiation oncologist. Many techniques, dose schedules and
      modifications in total skin electron irradiation (TSEI) have been tried since
      1950s. TSEI treatment is a very time consuming, inconvenient and physically
      challenging to both patient as well as oncologist. AIM: At our center TSEI was
      performed since 1983 with conventional linear accelerator where the treatment
      time was prolonged beyond two hours, which was very difficult or the patient,
      oncologist, technical officer and eating away the machine time hampering the
      treatment of other patients. From 1998 we shifted to high dose rate (HDR) mode,
      in order to bring down the treatment time of a single patient every day from two
      and half hour to 15 min. The reduction of treatment time increases patient
      compliance and at the same time saved machine time. MATERIALS AND METHODS:
      Between 1998 and 2003, eleven pathological diagnosed MF patients were treated
      using HDR TSEI. All the patients were male between 40 and 70 years of age, who
      had the history of having the disease for 7-22 months. Four patients had T2 and
      seven patients had T3 stage disease with more than 90% skin surface involvement.
      TSEI was performed with 4 MeV electrons with a daily fraction size of 120 cGy to
      a total dose of 36 Gy. At the end of 36 Gy, boost dose of 10 Gy was delivered to
      self shielding regions like sole, scalp and perineum. Considering the treatment
      related toxicities and consequent treatment interruptions, in the first seven
      patients, the last four patients were treated using similar HDR TSEI technique
      with modified treatment schedule, where the treatment was given on an alternate
      day basis following 2nd week of initiation of treatment. RESULTS: The patients
      were followed over a period of 144 months with a median of 72 months. Nine
      patients are alive without any evidence of disease, one patient relapsed and one
      died due to progression of disease. The most common radiation related morbidities
      are erythema, skin blisters, various degree of desquamations, swelling of joints
      (specially small joints) etc. which are controlled by treatment interruptions and
      conservative measures. By modifying the treatment schedule, the incidence of
      toxicity as well as treatment interruptions were brought down. CONCLUSIONS: We
      can conclude that HDR-TSEI is an excellent and safe therapeutic modality for the
      patients with MF both curative as well as palliative without any added toxicity
      profile, provided patient positioning is done properly.

PMID- 24936330
TI  - First treatment of mycosis fungoides by total skin electron beam (TSEB) therapy
      in Greece.
AB  - BACKGROUND: Mycosis fungoides (MF), the most common subtype of cutaneous T-Cell
      Lymphoma (CTCL), is a rare chronic skin neoplasia. Total skin electron
      irradiation has been employed along with a variety of other topical or systemic
      treatments for MF management. AIM: To report the first case treated by TSEB
      irradiation protocol in Greece. MATERIALS AND METHODS: A fractionated 36 Gy total
      skin electron beam (TSEB) therapy was prescribed to a 65-years-old male patient
      with mycosis fungoides (MF), stage IIB, refractory to several treatments during a
      20-year period. Dose uniform delivery was monitored by thermo-luminescence
      dosimetry. RESULTS AND DISCUSSION: The homogeneous skin dose distribution
      resulted in a complete clinical response. Limited, irradiation-oriented, side
      effects appeared. CONCLUSIONS: The first TSEB irradiation prescription in Greek
      medical chronicles was proved effective in this case of tumor stage MF (T3-IIB),
      which had been refractory to several single or combination treatments.

PMID- 24936331
TI  - Institutional experience with a rotational total skin electron irradiation
      (RTSEI) technique-A three decade review (1981-2012).
AB  - Total skin electron irradiation (TSEI) for patients with cutaneous lymphomas is
      technically challenging, and numerous approaches have been developed to overcome
      the many field matching problems associated with such a large and complex
      treatment volume. Since 1981 we have delivered TSEI using a rotational total skin
      electron irradiation (RTSEI) technique in conjunction with patch, treat and boost
      fields in order to provide complete skin and dose coverage. Initially we used a 6
      MeV electron beam at an extended source-skin distance (SSD) on a modified linear
      accelerator. More recently we began using a high dose rate electron mode on a
      commercially available linear accelerator. The RTSEI technique allows the
      delivery of a seamless surface dose to the majority of the patient's skin surface
      in a single treatment. In this review paper we present our three-decade
      experience with the technical development, dosimetry, treatment delivery and
      clinical outcomes of our RTSEI technique. 

PMID- 24936333
TI  - Review of the results of the in vivo dosimetry during total skin electron beam
      therapy.
AB  - This work reviews results of in vivo dosimetry (IVD) for total skin electron beam
      (TSEB) therapy, focusing on new methods, data emerged within 2012. All quoted
      data are based on a careful review of the literature reporting IVD results for
      patients treated by means of TSEB therapy. Many of the reviewed papers refer
      mainly to now old studies and/or old guidelines and recommendations (by IAEA,
      AAPM and EORTC), because (due to intrinsic rareness of TSEB-treated pathologies)
      only a limited number of works and reports with a large set of numerical data and
      proper statistical analysis is up-to-day available in scientific literature.
      Nonetheless, a general summary of the results obtained by the now numerous IVD
      techniques available is reported; innovative devices and methods, together with
      areas of possible further and possibly multicenter investigations for TSEB
      therapies are highlighted. 

PMID- 24936332
TI  - Technical and dosimetric aspects of the total skin electron beam technique
      implemented at Heidelberg University Hospital.
AB  - AIM: To give a technical description and present the dosimetric proporties of the
      total skin electron beam technique implemented at Heidelberg University Hospital.
      BACKGROUND: Techniques used for total skin electron beam irradiation were
      developed as early as in the 1960s to 1980s and have, since then, hardly changed.
      However, new measurements of the established methods allow deeper insight into
      the dose distributions and reasons for possible deviations from uniform dose.
      MATERIALS AND METHODS: The TSEI technique applied at Heidelberg University
      Hospital since 1992 consists of irradiating the patient with a superposition of
      two beams of low energy electrons at gantry angles of 72 degrees  and 108 degrees
      while he is rotating in a standing position on a turntable at 370 cm distance
      from the accelerator. The energy of the electron beam is degraded to 3.9 MeV by
      passing through an attenuator of 6 mm of Perspex. A recent re-measurement of the
      dose distribution is presented using modern dosimetry tools like a linear array
      of ionization chambers in combination with established methods like
      thermoluminescent detectors and film dosimetry. RESULTS: The measurements show a
      strong dependence of dose uniformity on details of the setup like gantry angles.
      CONCLUSIONS: Dose uniformity of -4/+8% to the majority of the patient's skin can
      be achieved, however, for the described rotational technique overdoses up to more
      than 20% in small regions seem unavoidable.

PMID- 24936334
TI  - Psychosocial and legal aspects of oncological treatment in patients with
      cognitive impairment.
AB  - With society getting older and affected by many diseases, more and more people
      suffer from severe cognitive disorders. As practice shows, the legal situations
      of such people is often problematic. This is due to a number of factors, such as
      short time since the deterioration of patient's condition, initial symptoms
      ignored, social prejudice towards the idea of incapacitation or taking decisions
      for a patient, complicated procedures and, sometimes, insufficient knowledge of
      legal regulations. Cognitive disorders also occur in patients treated for cancer.
      To be effective, oncological treatment needs to be started as early as possible.
      This, however, does not meet the criteria of sudden threat to life. The present
      article relates to both the psychosocial and legal aspects of care of people
      suffering from intense disorders of memory, attention, problem solving, executive
      functions, and other. Surely, physicians know how to handle patients with the
      above dysfunctions. However, legal procedures aimed to protect patients' rights
      are often unclear and time consuming. In practice, this often amounts to a
      dilemma whether to treat or follow the applicable law. Certainly, solutions in
      this regard should be clearer and better adapted to the needs arising from
      specific treatment needs of particular groups of patients. 

PMID- 24936336
TI  - Radiation therapy in the last month of life.
AB  - AIM: We sought to survey a large, multi-center patient sample to better
      characterize/quantify RT utilization at the end of life. BACKGROUND: Few
      objective data exist for radiation therapy (RT) delivery at end of life (EOL).
      MATERIALS AND METHODS: Data were retrieved for all patients receiving RT in
      calendar year 2010 in the Department of Radiation Oncology at Indiana University
      (IU) and Howard University (HU) hospitals. Specific attention was made of the
      group of patients receiving RT in the last 30 days of life. RESULTS: A total of
      852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At
      time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients
      (6.3% of total; 30% of expired patients) died within 30 days of receiving their
      last treatment. Twenty patients (2.3% of total; 11.2% of expired patients)
      received RT within their last week of life. For both sites, the median time until
      death from completion of therapy was 12.5 days (range 2-30 days). CONCLUSIONS:
      Radiation in the last month of life is likely to provide minimal palliation or
      survival benefit. This, coupled with the financial implications, time investment,
      and physical costs, suggests that physicians and patients should more strongly
      consider hospice, and minimize duration of palliative RT courses as far as
      possible. As with chemotherapy, RT utilization at EOL should be considered for
      collection as an overuse metric.

PMID- 24936335
TI  - Clinicopathological features and prognosis of triple negative breast cancer in
      Kuwait: A comparative/perspective analysis.
AB  - AIM: The aim of this study was to determine the incidence of TNBC in Kuwait, to
      analyze the clinicopathologic features and prognosis of this type of breast
      cancer, and compare it with reports from other regions of the world. BACKGROUND:
      Triple negative breast cancer (TNBC) is defined as a subtype that is negative for
      estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor 2 (HER2). There is a growing evidence of the heterogeneity of such
      entity on the molecular level that may cause discrete outcomes. METHODS: We
      analyzed the clinicopathologic features of 363 TNBC cases which were diagnosed in
      Kuwait from July 1999 to June 2009. The disease-free survival (DFS) and overall
      survival (OS) were analyzed by Kaplan-Meier method. Comparison was done with
      reports from USA, Europe, Middle and Far East. RESULTS: Among 2986 patients
      diagnosed with breast cancer in Kuwait, 363 patients (12.2%) were TNBC. The
      median age was 48 years, 57.2% had lymph nodes (LN) metastasis, 56.9% were of
      grade III tumor and 41.9% had stage II disease. 81% developed recurrences and 75%
      of deaths occurred by 2.5 years after treatment. There is marked variation of
      clinicopathologic features according to country of patients' cohort. CONCLUSION:
      The incidence of TNBC in our study is similar to other studies. TNBC patients
      showed an early major recurrence surge peaking at approximately year 2.5.
      Regional variation of clinicopathologic features indicates a need for molecular
      studies to define underlying molecular features and its impact on survival.

PMID- 24936337
TI  - An institutional experience of quality assurance of a treatment planning system
      on photon beam.
AB  - AIM: The purpose of the present study is to show the application of the IAEA TRS
      430 QA procedures of EclipseTMv7.5 TPS for photon energies. In addition, the
      trends of the deviations found in the conducted tests were determined.
      BACKGROUND: In the past, the lack of complete TPS QA procedures led to some
      serious accidents. So, QA in the radiotherapy treatment planning process is
      essential for determination of accuracy in the radiotherapy process and avoidance
      of treatment errors. MATERIALS AND METHODS: The calculations of TPS and
      measurements of irradiations of the treatment device were compared in the study.
      As a result, the local dose deviation values (delta 1: central beam axis, delta
      2: penumbra and build up region, delta 3: inside field, delta 4: outside beam
      edges, delta 50-90: beam fringe, RW50: radiological width) and their confidence
      limit values (including systematic and random errors) were obtained. RESULTS: The
      confidence limit values of delta 4 were detected to increase with expanding field
      size. The values of delta 1 and delta 3 of hard wedge were larger than open
      fields. The values of delta 2 and delta 50-90 of the inhomogeneity effect test
      were larger, especially than other tests of this study. The average deviation was
      showed to increase with the rise of the wedge angle. The values of delta 3 and
      delta 4 of lung irradiation were outside tolerance. CONCLUSIONS: The QA of TPS
      was done and it was found that there were no reservations in its use in patient
      treatment. The trend of the deviations is shown.

PMID- 24936338
TI  - Modeling the time dependent biodistribution of Samarium-153 ethylenediamine
      tetramethylene phosphonate using compartmental analysis.
AB  - AIM: The main purpose of this work was to develop a pharmacokinetic model for the
      bone pain palliation agent Samarium-153 ethylenediamine tetramethylene
      phosphonate ([(153)Sm]-EDTMP) in normal rats to analyze the behavior of the
      complex. BACKGROUND: The use of compartmental analysis allows a mathematical
      separation of tissues and organs to determine the concentration of activity in
      each fraction of interest. Biodistribution studies are expensive and difficult to
      carry out in humans, but such data can be obtained easily in rodents. MATERIALS
      AND METHODS: We have developed a physiologically based pharmacokinetic model for
      scaling up activity concentration in each organ versus time. The mathematical
      model uses physiological parameters including organ volumes, blood flow rates,
      and vascular permabilities; the compartments (organs) are connected anatomically.
      This allows the use of scale-up techniques to predict new complex distribution in
      humans in each organ. RESULTS: The concentration of the radiopharmaceutical in
      various organs was measured at different times. The temporal behavior of
      biodistribution of (153)Sm-EDTMP was modeled and drawn as a function of time.
      CONCLUSIONS: The variation of pharmaceutical concentration in all organs is
      described with summation of 6-10 exponential terms and it approximates our
      experimental data with precision better than 2%.

PMID- 24936339
TI  - Primary angiosarcoma of the breast complicated by the syndrome of disseminated
      intravascular coagulation (DIC): Case report and literature review.
AB  - Primary angiosarcoma of the breast (PAB) accounts for 0.04% of all breast
      malignant tumors. It affects young women usually at third or fourth decades of
      life. PAB clinically manifests as a painless, movable mass with sharp limits. A
      bluish red discoloration of the overlying skin is often observed. Enlargement of
      axillary lymph nodes generally does not occur. Angiosarcoma of the breast has a
      very poor prognosis due to the tendency to metastasize haematogenously and high
      frequency of local recurrence. Mastectomy and chemotherapy are preferable
      treatment choices. This paper presents a case of primary angiosarcoma of the
      breast with a syndrome of disseminated intravascular coagulation (DIC). 

PMID- 24936341
TI  - Comparative analysis of image guidance in two institutions for prostate cancer
      patients.
AB  - AIM/BACKGROUND: The analysis of systematic and random errors obtained from the
      pooled data on inter-fraction prostate motion during radiation therapy in two
      institutions. MATERIALS AND METHODS: Data of 6085 observations for 216 prostate
      cancer patients treated on tomotherapy units in two institutions of position
      correction shifts obtained by co-registration of planning and daily CT studies
      were investigated. Three independent variables: patient position (supine or
      prone), target (prostate or prostate bed), and imaging mode (normal or coarse)
      were analyzed. Systematic and random errors were evaluated and used to calculate
      the margins for different options of referencing based on the position
      corrections observed with one, three, or five imaging sessions. RESULTS:
      Statistical analysis showed that only the difference between normal and coarse
      modes of imaging was significant, which allowed to merge the supine and prone
      position sub-groups as well as the prostate and prostate bed patients. In the
      normal and coarse imaging groups, the margins calculated using systematic and
      random errors in the medio-lateral and cranio-caudal directions (5.5 mm and 4.5
      mm, respectively) were similar, but significantly different (5.3 mm for the
      normal mode and 7.1 mm for the coarse mode) in the anterio-posterior direction.
      The reference scheme based on the first three fractions (R3) was found to be the
      optimal one. CONCLUSIONS: The R3 reference scheme effectively reduced systematic
      and random errors. Larger margins in the anterio-posterior direction should be
      used during prostate treatment on the tomotherapy unit, as coarse imaging mode is
      chosen in order to reduce imaging time and dose.

PMID- 24936340
TI  - Breast cancer: Actual methods of treatment and future trends.
AB  - The recent ten to twenty years have seen a substantial progress in the diagnosis
      and treatment of breast cancer. A rapid development of various curative options
      has led to the improvement of treatment outcomes, while paying more and more
      attention to the aspects of quality of life and cosmetic effect. In our
      publication, we wish to outline certain trends in the development of modern
      treatment of breast cancer. Among topics discussed are new forms of molecular
      diagnostics, new approach to the idea of sentinel node biopsy, as well as new
      techniques for delivery of medical procedures, the increasing use of nomograms,
      progress in the techniques of breast conservative treatment, modern approach to
      occult breast lesions, the increasing use of neoadjuvant treatment and
      intraoperative radiotherapy. 

PMID- 24936343
TI  - Anti-Allergic Effects of Kakrol (Momordica dioica Roxb.) Flesh Extract.
AB  - We examined the inhibitory effect of the extract of kakrol extracted by 3 types
      of solvent (water, 50% and 100% ethanol) on histamine release in human basophilic
      KU812 cells. The water extract of kakrol flesh showed the strongest inhibitory
      effect on histamine release as compared with the other extracts. Therefore, we
      evaluated whether water extract of kakrol flesh had a suppressive effect on
      development of atopic dermatitis-like lesions in picryl chloride-treated NC/Nga
      mice. The dietary kakrol flesh water extract alleviated the development of skin
      lesions in ears accompanied by lower IgE levels and inflammatory cytokines levels
      in serum. These results indicate that the water extract of kakrol flesh might
      have therapeutic potential for allergic responses in vitro and in vivo. 

PMID- 24936342
TI  - Extracorporeal life support for patients with acute respiratory distress
      syndrome: report of a Consensus Conference.
AB  - The influenza H1N1 epidemics in 2009 led a substantial number of people to
      develop severe acute respiratory distress syndrome and refractory hypoxemia. In
      these patients, extracorporeal membrane oxygenation was used as rescue
      oxygenation therapy. Several randomized clinical trials and observational studies
      suggested that extracorporeal membrane oxygenation associated with protective
      mechanical ventilation could improve outcome, but its efficacy remains uncertain.
      Organized by the Societe de Reanimation de Langue Francaise (SRLF) in conjunction
      with the Societe Francaise d'Anesthesie et de Reanimation (SFAR), the Societe de
      Pneumologie de Langue Francaise (SPLF), the Groupe Francophone de Reanimation et
      d'Urgences Pediatriques (GFRUP), the Societe Francaise de Perfusion (SOFRAPERF),
      the Societe Francaise de Chirurgie Thoracique et Cardiovasculaire (SFCTV) et the
      Sociedad Espanola de Medecina Intensiva Critica y Unidades Coronarias (SEMICYUC),
      a Consensus Conference was held in December 2013 and a jury of 13 members wrote
      65 recommendations to answer the five following questions regarding the place of
      extracorporeal life support for patients with acute respiratory distress
      syndrome: 1) What are the available techniques?; 2) Which patients could benefit
      from extracorporeal life support?; 3) How to perform extracorporeal life
      support?; 4) How and when to stop extracorporeal life support?; 5) Which
      organization should be recommended? To write the recommendations, evidence-based
      medicine (GRADE method), expert panel opinions, and shared decisions taken by all
      the thirteen members of the jury of the Consensus Conference were taken into
      account. 

PMID- 24936344
TI  - Identification of Immunopotentiating Lactic Acid Bacteria that Induce Antibody
      Production by in vitro Stimulated Human Peripheral Blood Mononuclear Cells.
AB  - L-leucyl-L-leucine methyl ester (LLME) is known to remove lysosome-rich cells
      from human peripheral blood mononuclear cells (PBMCs). To evaluate the
      immunopotentiating ability of lactic acid bacteria (LAB), we adopted the in vitro
      stimulation protocol of LLME-treated PBMCs as a model assay system and monitored
      the level of antibody produced by stimulated PBMCs. The results indicated that
      several LAB strains have immunopotentiating ability against PBMCs, as evidenced
      by the enhanced antibody production and increased number of antigen-specific B
      cells. Next, we identified T cells as the direct target cells of the
      immunopotentiating LAB strain L32, suggesting that L32 induced antibody
      production by PBMCs through T-cell activation. Finally, we tested the
      immunopotentiating ability of ligands for Toll-like receptor 2 (TLR2), which is
      known to mediate the LAB signal, and observed that both L32 and one of the TLR2
      ligands, LTA-BS, induced antigen-specific antibody production by in vitro
      stimulated PBMC. This suggests that L32 and LTA-BS can be used as an adjuvant for
      stimulating immune reaction in PBMCs. 

PMID- 24936345
TI  - Technological advances in bifidobacterial molecular genetics: application to
      functional genomics and medical treatments.
AB  - Bifidobacteria are well known as beneficial intestinal bacteria that exert health
      promoting effects in humans. In addition to physiological and immunological
      investigations, molecular genetic technologies have been developed and have
      recently started to be applied to clarify the molecular bases of host
      Bifidobacterium interactions. These technologies include transformation
      technologies and Escherichia coli-Bifidobacterium shuttle vectors that enable
      heterologous gene expression. In this context, a plasmid artificial modification
      method that protects the introduced plasmid from the restriction system in host
      bifidobacteria has recently been developed to increase transformation efficiency.
      On the other hand, targeted gene inactivation systems, which are vital for
      functional genomics, seemed far from being practically applicable in
      bifidobacteria. However, remarkable progress in this technology has recently been
      achieved, enabling functional genomics in bifidobacteria. Integrated use of these
      molecular genetic technologies with omics-based analyses will surely boost
      characterization of the molecular basis underlying beneficial effects of
      bifidobacteria. Applications of recombinant bifidobacteria to medical treatments
      have also progressed. 

PMID- 24936346
TI  - Complexing of Green Tea Catechins with Food Constituents and Degradation of the
      Complexes by Lactobacillus plantarum.
AB  - Complexing of green tea catechins with food constituents and their hydrolysis by
      tannase-producing Lactobacillus plantarum strains, were investigated. Our
      observations indicated that 1) epigallocatechin gallate (EGCg) and other catechin
      galloyl esters bound with food ingredients (i.e., proteins) to form a complex
      that is likely to be unabsorbable through the intestinal wall, whereas most
      catechins not esterified with gallic acid (GA) remain in free form, not
      complexing with food ingredients; 2) tannase activity of L. plantarum is strain
      dependent, possibly grouped into those with high tannase activity hydrolyzing
      EGCg to epigallocatechin and GA and those with the low activity; and 3) L.
      plantarum strains with high tannase activity are capable of hydrolyzing not only
      intact EGCg but also EGCg and other catechin galloyl esters complexed with
      dietary proteins to free non-galloyl ester catechins and GA. The evidence
      suggests that L. plantarum with high tannase activity, if it colonizes the human
      intestine, would release free non-galloyl-ester catechins and GA that are readily
      absorbed through the human intestinal epithelia from the complexes, thereby
      ensuring maximum delivery of the bioactive polyphenols of green tea to the host. 

PMID- 24936348
TI  - Effect of Lacto-N-biose I on the Antigen-specific Immune Responses of
      Splenocytes.
AB  - We examined the effect of lacto-N-biose I (LNB) on Antigen (Ag)-specific
      responses of immune cells. LNB exposure in vitro suppressed Ag-specific
      Interleukin (IL)-4 secretion of mouse splenocytes significantly. However, IL-4
      secretion from CD4(+) T cells stimulated with anti-CD3epsilon did not changed
      significantly with LNB exposure. Additionally, Ag-specific Th1 cytokines did not
      change. Therefore LNB might suppress Ag-specific IL-4 through modification of Ag
      presenting cells (APCs) in a manner independent of Th1-type immune development. 

PMID- 24936347
TI  - Evaluation of the effects of dietary organic germanium, ge-132, and raffinose
      supplementation on caecal flora in rats.
AB  - Poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) is the most common
      organic germanium compound. The ingestion of Ge-132 promotes bile secretion. We
      assessed the rat caecal characteristics after the administration of Ge-132 and
      raffinose, a prebiotic oligosaccharide, because both Ge-132 and some prebiotics
      can change the fecal color to yellow. We also compared the changes in the caecal
      flora caused by the two compounds. In addition, we evaluated the simultaneous
      administration of Ge-132 and raffinose and their effects on beta-glucuronidase
      activity, which is known to be a factor related to colon cancer. Male Wistar rats
      (three weeks old) were given one of the following diets: 1) a control diet
      (control group), 2) a diet containing 0.05% Ge-132 (Ge-132 group), 3) a diet
      containing 5% raffinose (RAF group) or 4) a diet containing 0.05% Ge-132 + 5%
      raffinose (GeRAF group). The Bifidobacterium, Lactobacillus and total bacteria
      counts were significantly increased by the dietary raffinose, and Ge-132 did not
      suppress this increase. The raffinose intake increased caecal acetic acid
      production significantly. The activity of beta-glucuronidase in the caecal
      contents was increased by dietary Ge-132, whereas dietary raffinose decreased the
      beta-glucuronidase activity significantly. These results indicate that the
      simultaneous intake of dietary raffinose and Ge-132 does not inhibit the effects
      of either compound on intestinal fermentation and bile secretion. Additionally,
      the simultaneous intake of both raffinose and Ge-132 could abrogate the increase
      in beta-glucuronidase activity induced by Ge-132 alone. 

PMID- 24936349
TI  - Reduced Expression of Polymeric Immunoglobulin Receptors in the Intestine of
      Young Rats Fed a Fiber-free Diet.
AB  - In this study, we investigated the influence of a fiber-free diet on the
      intestinal secretory immune system in young animals. Four-week-old rats were fed
      either a purified diet containing sucrose as the only carbohydrate source (fiber(
      ) diet) or a diet supplemented with 15% natural crude fiber from sugar beets
      (fiber(+) diet). After 14 days of feeding, we measured total IgA content in 24-hr
      fecal samples and in intestinal tissues and the expression of intestinal
      polymeric immunoglobulin receptors (pIgRs), which are essential for IgA
      secretion. The excretion of total IgA in the feces was significantly lower in
      rats fed the fiber(-) diet than in those fed the fiber(+) diet (27% vs. 100%; p <
      0.05). However, the total IgA content in the intestinal tissue extracts did not
      differ between the groups. The pIgR signal intensities observed by
      immunohistochemistry were somewhat lower in the colon of the rats fed the fiber(
      ) diet. Western blot analysis showed that pIgR protein expression in the distal
      colon of rats fed the fiber(-) diet was significantly lower than that in rats fed
      the fiber(+) diet (38% vs. 100%, p < 0.05). Conversely, colonic pIgR mRNA
      expression did not differ between the groups. Thus, we conclude that a fiber-free
      diet decreases colonic pIgR protein expression by a posttranscriptional
      mechanism, resulting in decreased luminal secretory immune system activity and
      thus, suboptimal protection of the colonic mucosa. 

PMID- 24936350
TI  - Effect of Dietary l-arabinose on the Intestinal Microbiota and Metabolism of
      Dietary Daidzein in Adult Mice.
AB  - This study examined the effects of L-arabinose on mouse intestinal microbiota and
      urinary isoflavonoids. Male mice were randomly divided into two groups: those fed
      a 0.05% daidzein-2.5% L-arabinose diet (AR group) and those fed a 0.05% daidzein
      control diet (CO group) for 28 days. The amounts of daidzein detected in urine
      were significantly lower in the AR group than in the CO group. The ratio of
      equol/daidzein was significantly higher in the AR group (p<0.01) than in the CO
      group. The composition of caecal flora differed between the AR and CO groups. The
      occupation ratios of Prevotella and Lactobacillales were significantly lower in
      the AR group. This study suggests that dietary L-arabinose has the potential to
      affect the metabolism of equol from daidzein by altering the metabolic activity
      of intestinal microbiota. 

PMID- 24936351
TI  - Cell Wall Polysaccharides of Candida albicans Induce Mast Cell Degranulation in
      the Gut.
AB  - We investigated Candida albicans-induced mast cell degranulation in vitro and in
      vivo. Cell wall fraction but not culture supernatant and cell membrane fraction
      prepared from hyphally grown C. albicans induced beta-hexosaminidase release in
      RBL-2H3 cells. Cell wall mannan and soluble beta-glucan fractions also induced
      beta-hexosaminidase release. Histological examination of mouse forestomach showed
      that C. albicans gut colonization induces mast cell degranulation. However,
      intragastric administration of cell wall fraction failed to induce mast cell
      degranulation. We propose that cell wall polysaccharides are responsible for mast
      cell degranulation in the C. albicans-colonized gut. 

PMID- 24936352
TI  - Can Colonoscopy Aspirates be a Substitute for Fecal Samples in Analyses of the
      Intestinal Microbiota?
AB  - There is a growing interest in the study of the human gut microbiota, as
      correlations between changes in bacterial profiles and diseases are increasingly
      discovered. Studies in this field generally use fecal samples, but it is often
      easier to obtain colon content aspirates during colonoscopy. This study used
      automated ribosomal internal spacer analysis (ARISA) to examine the extent to
      which the microbiota of colon aspirate samples obtained after bowel cleansing can
      reflect interindividual differences and serve as a proxy for fecal samples. Pre
      bowel preparation fecal samples as well as colonoscopy aspirate samples from the
      cecum and rectum were obtained from 19 subjects. DNA was extracted from all
      samples, and comparative analysis was performed, including analysis of similarity
      (ANOSIM) and nonmetric multidimensional scaling. ANOSIM confirmed that samples
      from the same individual were well separated from samples from different
      individuals. Significantly larger differences were found between samples from
      different individuals than between samples of the same individual (R = 0.7605, p
      < 0.0001). These findings show that post-bowel preparation aspirates maintain a
      strong individual signature. Colonoscopy aspirates can therefore serve as a
      substitute for fecal samples in studies comparing the microbiota of different
      clinical study groups, especially when fecal samples are unavailable. 

PMID- 24936353
TI  - Gut Colonization by Candida albicans Inhibits the Induction of Humoral Immune
      Tolerance to Dietary Antigen in BALB/c Mice.
AB  - We previously observed that gut colonization by Candida albicans promoted serum
      antibody response to orally administered ovalbumin in mice. We therefore
      postulated that C. albicans affects oral tolerance induction. The present study
      tested this idea. BALB/c mice were intragastrically administered with either C.
      albicans (1 * 10(7)) or vehicle, and the colonization was confirmed by weekly
      fecal cultures. Mice were further divided into two subgroups and intragastrically
      administered with either ovalbumin (20 mg) or vehicle for five consecutive days.
      Thereafter, all mice were intraperitoneally immunized with ovalbumin in alum. In
      mice without C. albicans inoculation, ovalbumin feeding prior to immunization
      significantly suppressed the increase in ovalbumin-specific IgE, IgG1 and IgG2a
      in sera, suggesting oral tolerance induction. In C. albicans-inoculated mice,
      however, the antibody levels were the same between ovalbumin- and vehicle-fed
      mice. In contrast, ovalbumin feeding significantly suppressed cellular immune
      responses, as evidenced by reduced proliferation of splenocytes restimulated by
      ovalbumin ex vivo, in both C. albicans-inoculated and uninoculated mice. Ex vivo
      supplementation with neither heat-killed C. albicans nor the culture supernatant
      of C. albicans enhanced the production of ovalbumin-specific IgG1 in splenocytes
      restimulated by the antigen. These results suggest that gut colonization by C.
      albicans inhibits the induction of humoral immune tolerance to dietary antigen in
      mice, whereas C. albicans may not directly promote antibody production. We
      therefore propose that C. albicans gut colonization could be a risk factor for
      triggering food allergy in susceptible individuals. 

PMID- 24936354
TI  - Persistence of orally administered lactobacillus strains in the gut of infant
      mice.
AB  - The present study tested the persistence of orally administered bacteria in the
      gut of suckling mice. We used three bacterial strains: one strain of
      Lactobacillus johnsonii (designated strain Ms1) that was previously isolated from
      the mouse stomach, and two strains of L. plantarum, (strain No. 14 and JCM
      1149(T)). We detected L. johnsonii Ms1, but neither strain of L. plantarum, in
      the gut 7 days after administration when the organisms were administered on days
      0, 1, 3 or 7 of neonatal life. None of the strains was detected in the gut 7 days
      after the administration on days 14 or 28 of neonatal life. L. johnsonii Ms1 and
      L. plantarum JCM 1149(T) exhibited similar levels of in vitro association with
      gut tissues, with both strains showing association that was significantly higher
      than that of L. plantarum No. 14. In a separate experiment, the number of total
      bacteria and lactobacilli in the gut, as estimated by real-time quantitative PCR,
      was significantly higher in 14- and 21-day-old mice than in 0- and 7-day-old
      mice. In addition, the number of total bacteria was higher in 21-day-old mice
      than in 14-day-old mice, and the number of lactobacilli was higher in 7-day-old
      mice than in 0-day-old mice. These results suggest that gut persistence of
      administered bacteria in infant mice is species- or strain-specific and is
      affected by the development of indigenous microbiota. In addition, gut
      persistence of administered bacteria may not always depend on the tissue
      association capacity. 

PMID- 24936355
TI  - Receptor-like Molecules on Human Intestinal Epithelial Cells Interact with an
      Adhesion Factor from Lactobacillus reuteri.
AB  - A surface protein of Lactobacillus reuteri, mucus adhesion-promoting protein
      (MapA), is considered to be an adhesion factor. MapA is expressed in L. reuteri
      strains and adheres to piglet gastric mucus, collagen type I, and human
      intestinal epithelial cells such as Caco-2. The aim of this study was to identify
      molecules that mediate the attachment of MapA from L. reuteri to the intestinal
      epithelial cell surface by investigating the adhesion of MapA to receptor-like
      molecules on Caco-2 cells. MapA-binding receptor-like molecules were detected in
      Caco-2 cell lysates by 2D-PAGE. Two proteins, annexin A13 (ANXA13) and paralemmin
      (PALM), were identified by MALDI TOF-MS. The results of a pull-down assay showed
      that MapA bound directly to ANXA13 and PALM. Fluorescence microscopy studies
      confirmed that MapA binding to ANXA13 and PALM was colocalized on the Caco-2 cell
      membrane. To evaluate whether ANXA13 and PALM are important for MapA adhesion,
      ANXA13 and PALM knockdown cell lines were established. The adhesion of MapA to
      the abovementioned cell lines was reduced compared with that to wild-type Caco-2
      cells. These knockdown experiments established the importance of these receptor
      like molecules in MapA adhesion. 

PMID- 24936356
TI  - Suppressive Effect of High Hydrogen Generating High Amylose Cornstarch on
      Subacute Hepatic Ischemia-reperfusion Injury in Rats.
AB  - We examined whether feeding high hydrogen generating resistant starch could
      suppress subacute hepatic ischemia-reperfusion injury. Rats were fed a control
      diet with or without 20% high amylose cornstarch (HAS) supplementation for 14
      days. On day 12, rats were subject to ischemia-reperfusion treatment. Portal
      hydrogen concentration was higher in the HAS group compared with the control
      group. Increased plasma alanine and aspartate aminotransferase activities due to
      ischemia-reperfusion treatment tended to decrease, and a significant reduction
      was observed by HAS feeding when compared with the control group. In conclusion,
      HAS, which enhances hydrogen generation in the hindgut, alleviated subacute
      hepatic ischemia-reperfusion injury. 

PMID- 24936358
TI  - Effects of Enteric-coated Lactoferrin Tablets Containing Lactobacillus brevis
      subsp. coagulans on Fecal Properties, Defecation Frequency and Intestinal
      Microbiota of Japanese Women with a Tendency for Constipation: a Randomized
      Placebo-controlled Crossover Study.
AB  - The effects of oral administration of enteric-coated tablets containing
      lactoferrin (LF; 100 mg/tablet) and heat-killed Lactobacillus brevis subsp.
      coagulans FREM BP-4693 (LB; 6*10(9) bacteria/tablet) on fecal properties were
      examined in 32 Japanese women (20-60 years of age) with a tendency for
      constipation (defecation frequency at equal to or less than 10 times/2 weeks) by
      a double-blind placebo-controlled crossover design. A significant increase in
      defecation days per week was obserbed in the subjects who ingested the tablets
      containing LF and LB compared with the placebo group. The number of
      bifidobacteria in feces also significantly increased compared with the placebo
      group. In an in vitro study, LF and tryptic hydrolysate of LF, but not peptic
      hydrolysate of LF, upregulated the growth of Bifidobacterium longum ATCC15707
      when added to the culture. These results demonstrate the capability of the
      enteric-coated tablets containing LF and LB in improving intestinal function and
      suggest that they have a growth promoting function for bifidobacteria. 

PMID- 24936357
TI  - Effects of diet on gut microbiota profile and the implications for health and
      disease.
AB  - Gut microbes are present in large concentrations on the human intestinal mucosal
      surface and play important roles in health and disease of the host. Numerous
      groups of gut microbes are associated with immunological and metabolic diseases
      and in maintaining health status of the host. Among these health- and disease
      associated gut microbes, Bacteroides, Clostridium and Bifidobacterium appear
      regularly in the list. Scientific and clinical evidence available to date
      indicates that diet is a major driving factor for the establishment of the gut
      microbiome. Slow digestible carbohydrates (human milk glycan, inulin and
      fructooligosaccharide), insoluble complex carbohydrates and protein diets favor
      the growth of Bacteroides, Clostridium and Bifidobacterium. Fat on the other hand
      suppresses the number of Bacteroides, Clostridium and Bifidobacterium; whereas
      polyphenols in general suppress Bacteroides and Clodtridium but enhance the
      Bifodobacterium. The implication is that dietary habits could be a major
      determinant of health and disease susceptibility. Dietary strategies could be an
      effective means of potentially inducing changes in intestinal microbiota and are
      certainly achievable, thus facilitating correction of intestinal microbiome
      aberrations or imbalances to improve our health. Most of the physiological and
      functional interactions between individual dietary components and the concoction
      of foods in a meal and gut microbiota have not yet been well studied. A concerted
      effort is required to acquire better understanding of their interaction in order
      to rationally maintain our intestinal microbiome homeostasis and general health
      through dietary intervention. 

PMID- 24936359
TI  - Effect of Formic Acid on Exopolysaccharide Production in Skim Milk Fermentation
      by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1.
AB  - In yogurt, the formation of formate by Streptococcus thermophilus stimulates the
      activity of Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus). However,
      there have been no reports how formic acid acts on the exopolysaccharide (EPS)
      production of L. bulgaricus. Here, the effect of formate on the EPS production in
      skim milk by L. bulgaricus OLL1073R-1 was investigated. After incubation for 24
      hr with 100 mg/l formate, cell proliferation and lactic acid production were
      accelerated. The viable and total cell numbers were increased about ten- and four
      fold, respectively. The amount of EPS in culture with formate (~116 ug/ml) was
      also four-fold greater than that of the control (~27 ug/ml). Although elongation
      of cells was observed at 6 hr of cultivation in both cultures, cells cultivated
      with formate returned to a normal shape after incubation for 24 hr. The
      sensitivity to cell wall hydrolase and composition of surface layer proteins, as
      well as the cell membrane fatty acid composition of L. bulgaricus OLL1073R-1,
      were not influenced by formate. However, differences were observed in
      intracellular fatty acid compositions and sensitivity to antibiotics. Cell length
      and surface damage returned to normal in cultures with formate. These
      observations suggest that formic acid is necessary for normal cell growth of L.
      bulgaricus OLL1073R-1 and higher EPS production. 

PMID- 24936360
TI  - Consecutive Intake of Fermented Milk Containing Bifidobacterium breve Strain
      Yakult and Galacto-oligosaccharides Benefits Skin Condition in Healthy Adult
      Women.
AB  - A double-blind, placebo-controlled, randomized trial was conducted to investigate
      the beneficial effect of probiotic and prebiotic fermented milk on the skin of
      healthy adult women. Forty healthy Japanese adult female volunteers with healthy
      skin randomly received either a bottle of probiotic and prebiotic fermented milk
      containing Bifidobacterium breve strain Yakult and galacto-oligosaccharides (GOS)
      (active group) or a non-fermented placebo milk containing neither probiotics nor
      GOS (placebo group) daily for 4 weeks. Before and after intake, hydration levels
      and cathepsin L-like activity in the stratum corneum and phenol levels in the
      serum and urine were determined. After intake, the hydration level of the stratum
      corneum decreased significantly in only the placebo group and was significantly
      lower than in the active group (p=0.031). Cathepsin L-like activity, an indicator
      of keratinocyte differentiation, was significantly increased in the active group
      (p=0.027). Serum and urine phenol levels decreased significantly in the active
      group (p=0.014, p=0.002, respectively), and serum phenol levels were
      significantly lower in the active group compared with the placebo group
      (p=0.006). The consecutive intake of probiotic and prebiotic fermented milk can
      benefit skin condition without dryness and decrease the levels of phenol
      production by gut bacteria in healthy adult women. 

PMID- 24936361
TI  - Influence of different probiotic lactic Acid bacteria on microbiota and
      metabolism of rats with dysbiosis.
AB  - Lactic acid bacteria (LAB) are often used for prevention and treatment of
      dysbiosis. However, the action of various strains of LAB on metabolism and
      digestion under these conditions are poorly understood. The purpose of this study
      was to investigate the influence of probiotic LAB on metabolism, digestion and
      microbiota in animals with dysbiosis. After administration of ampicillin and
      metronidazole male Wistar rats, were fed products containing Enterococcus faecium
      L3 (E.f.), Lactobacillus fermentum Z (L.f.) or milk (control 1). Animals in
      control group 2 were fed milk, after water instead of antibiotics. Dyspeptic
      symptoms disappeared after administration of probiotic compared with control 1.
      At the end of the experiment, an increase in the content of enterococci and
      lactobacilli in the proximal part of the small intestine was found in the animals
      treated with E.f. and L.f., respectively. After the introduction of probiotic
      enterococci, the quantity of lactobacilli and bifidobacteria in the intestines of
      rats increased, and the content of Klebsiella spp. and Escherichia coli decreased
      in comparison with the control group 1 and the group fed lactobacilli. The
      activity of alkaline phosphatase and aspartate transaminase was greater in blood
      serum of rats with dysbiosis receiving milk and lactobacilli. Intestinal alkaline
      phosphatase activity increased in the epithelium and chyme in the jejunum of the
      animals treated with L. f. and in the chyme only in the animals treated with E.
      f. Thus, the specific effects of different strains of probiotic LAB on the
      microbiota, and on metabolism and digestion of various nutrients were
      demonstrated. 

PMID- 24936362
TI  - Effect of Lactic Acid Bacteria on Lipid Metabolism and Fat Synthesis in Mice Fed
      a High-fat Diet.
AB  - Visceral fat accumulation is a major risk factor for the development of obesity
      related diseases, including diabetes, hyperlipidemia, hypertension, and
      arteriosclerosis. Stimulation of lipolytic activity in adipose tissue or
      inhibition of fat synthesis is one way to prevent these serious diseases. Lactic
      acid bacteria have an anti-obesity effect, but the mechanisms are unclear.
      Therefore, we evaluated the effect of the administration of lactic acid bacteria
      (Lactobacillus gasseri NT) on lipid metabolism and fat synthesis in a mouse high
      fat-diet model, focusing on visceral fat. Balb/c mice were fed a 45 kcal% fat
      diet for 13 weeks with and without a freeze-dried preparation of L. gasseri NT
      (10(9) CFU/g). An ex vivo glycerol assay with periovarian fat revealed that L.
      gasseri NT did not stimulate lipolytic activity. However, L. gasseri NT decreased
      the mRNA expression of sterol regulatory element-binding protein (SREBP) and its
      target gene fatty acid synthase (FAS) in the liver and decreased free fatty acid
      (FFA) in the blood. In conclusion, these findings indicated that administration
      of L. gasseri NT did not enhance lipid mobilization but can reduce fat synthesis,
      suggesting its potential for improving obesity-related diseases. 

PMID- 24936364
TI  - Up to Species-level Community Analysis of Human Gut Microbiota by 16S rRNA
      Amplicon Pyrosequencing.
AB  - Pyrosequencing-based 16S rRNA profiling has become a common powerful tool to
      obtain the community structure of gastrointestinal tract microbiota, but it is
      still hard to process the massive amount of sequence data into microbial
      composition data, especially at the species level. Here we propose a new approach
      in combining the quantitative insights into microbial ecology (QIIME), Mothur and
      ribosomal database project (RDP) programs to efficiently process 454 pyrosequence
      data to bacterial composition data up to the species level. It was demonstrated
      to precisely convert batch sequence data of 16S rRNA V6-V8 amplicons obtained
      from adult Singaporean fecal samples to taxonomically annotated biota data. 

PMID- 24936363
TI  - The pyrE Gene as a Bidirectional Selection Marker in Bifidobacterium Longum 105
      A.
AB  - We constructed a deletion mutant of the pyrE gene in Bifidobacterium longum 105
      A. A pyrE knockout cassette was cloned into pKKT427, a Bifidobacterium
      Escherichia coli shuttle vector, and then introduced into B. longum 105-A by
      electroporation. The transformants were propagated and spread onto MRS plates
      containing 5-fluoroorotic acid (5-FOA) and uracil. 5-FOA-resistant mutants were
      obtained at a frequency of 4.7 * 10(-5) integrations per cell. To perform pyrE
      gene complementation, the pyrE gene was amplified by PCR and used to construct a
      complementation plasmid (pKKT427-pyrE (+)). B. longum 105-A ?pyrE harboring this
      plasmid could not grow on MRS plates containing 5-FOA, uracil and spectinomycin.
      We also developed a chemically defined medium (bifidobacterial minimal medium;
      BMM) containing inorganic salts, glucose, vitamins, isoleucine and tyrosine for
      positive selection of pyrE transformants. B. longum 105-A ?pyrE could not grow on
      BMM agar, but the same strain harboring pKKT427-pyrE (+) could. Thus, pyrE can be
      used as a counterselection marker in B. longum 105-A and potentially other
      Bifidobacterium species as well. We demonstrated the effectiveness of this system
      by constructing a knockout mutant of the xynF gene in B. longum 105-A by using
      the pyrE gene as a counterselection marker. This pyrE-based selection system will
      contribute to genetic studies of bifidobacteria. 

PMID- 24936365
TI  - Identification of Heavy Smokers through Their Intestinal Microbiota by Data
      Mining Analysis.
AB  - The intestinal microbiota compositions of 92 Japanese men were identified
      following consumption of identical meals for 3 days, and collected feces were
      analyzed through terminal restriction fragment length polymorphism. The obtained
      operational taxonomic units and smoking habits of subjects were analyzed by a
      data mining software. The constructed decision tree was able to identify
      explicitly the groups of smokers and nonsmokers. In particular, 4 smokers, who
      smoked 20 cigarettes/day, i.e., heavy smokers, were gathered in the same group of
      the decision tree and were clearly identified. Related operational taxonomic unit
      were traced to understand the species of bacteria, but all were found to be
      uncultured bacteria. 

PMID- 24936367
TI  - KK/Ta Mice Administered Lactobacillus plantarum Strain No. 14 Have Lower
      Adiposity and Higher Insulin Sensitivity.
AB  - Excess accumulation of white adipose tissue can lead to obesity-related metabolic
      abnormalities such as insulin resistance. We previously reported that
      intragastric administration of Lactobacillus plantarum No. 14 reduced adipocyte
      size in diet-induced obese C57BL/6 mice. The present study tested whether L.
      plantarum No. 14 affects adiposity and insulin sensitivity in an animal model of
      type-2 diabetes mellitus. Male KK/Ta mice were fed a normal-fat diet and
      intragastrically given L. plantarum No. 14 (10(8) CFU/mouse) or vehicle daily for
      10 weeks. Interscapular brown adipose tissue and inguinal, mesenteric, and
      retroperitoneal white adipose tissue weights, serum leptin and insulin
      concentrations, and insulin resistance index (HOMA-IR) were significantly lower
      in L. plantarum No. 14-fed mice than in vehicle-fed mice. The sum of the
      inguinal, epididymal, mesenteric and retroperitoneal white adipose tissue weights
      correlated with serum leptin and non-esterified fatty acid concentrations and
      HOMA-IR. The mesenteric adipose tissue mRNA levels of monocyte chemoattractant
      protein-1 and tumor necrosis factor-alpha were significantly lower in L.
      plantarum No. 14-fed mice than in vehicle-fed mice. Mesenteric adipose tissue
      weight correlated with interleukin-6, monocyte chemoattractant protein-1, and
      tumor necrosis factor-alpha mRNA levels. HOMA-IR correlated with monocyte
      chemoattractant protein-1 and tumor necrosis factor-alpha mRNA levels. These data
      suggest that L. plantarum No. 14 prevents the development of insulin resistance,
      which is at least partly attributable to the prevention of obesity, in KK/Ta
      mice. 

PMID- 24936368
TI  - The Effect of Lactic Acid Bacteria-fermented Soybean Milk Products on Carrageenan
      induced Tail Thrombosis in Rats.
AB  - Thrombosis is characterized by congenital and acquired procatarxis. Lactic acid
      bacteria-fermented soybean milk products (FS-LAB) inhibit hepatic lipid
      accumulation and prevent atherosclerotic plaque formation. However, the
      therapeutic efficacy of FS-LAB against thrombosis has yet to be investigated. In
      this study, FS-LAB were administered subcutaneously into the tails of rats, with
      the subsequent intravenous administration of kappa-carrageenan 12 hr after the
      initial injection. In general, administration of kappa-carrageenan induces
      thrombosis. The length of the infarcted tail regions was significantly shorter in
      the rats administered a single-fold or double-fold concentration of the FS-LAB
      solution compared with the region in control rats. Therefore, FS-LAB exhibited
      significant antithrombotic effects. Our study is the first to characterize the
      properties of FS-LAB and, by testing their efficacy on an in vivo rat model of
      thrombosis, demonstrate the potency of their antithrombotic effect. 

PMID- 24936366
TI  - Gut microbiota, probiotics, and human health.
AB  - The review is devoted to the problems of microbiota and the ways of it correction
      employing beneficial life bacteria- probiotics. It covers the issues related to
      the functioning of human microbiota and its importance for the health, individual
      variability of microbial content, functioning of the probiotics in the human
      organism and the history of probiotic studies with particular focus on the
      microbiological investigations in the USSR. The article discusses the safety
      issues related to probiotics and the problems with probiotic therapy, trying to
      explain the reasons for the side effects caused by probiotics. The necessity of
      personified selection of the probiotic strain or individual microbial therapy
      autoprobiotics is also discussed. 

PMID- 24936370
TI  - Recollections of my young days: -the pleasure of creation-.
AB  - I was bashful by nature. In elementary school, I was enthusiastic about painting
      pictures, posters, and calligraphy, and making butterfly specimens and models.
      When I entered the middle school of Seikei Gakuen, I was fortunate to have good
      teachers and friends. Prof. Kusatao Nakamura taught us the "Preciousness of the
      pureness of heart", which is the principle of my life. After World War II, school
      classes reopened. I was deeply moved by the lecture of botany by Prof. Fumio
      Maekawa, and had a notion that I should like to make research my lifework. I went
      to high school and had the worries of my life. During that time, it was the book
      Gakusei ni atau by Prof. Eijirou Kawai, and a speech by Prof. Tadao Yanaihara,
      that sustained my heart. In 1953, I entered the postgraduate course of the
      University of Tokyo, and received the guidance of Prof. Yuichi Ochi. This matter
      was decisive for my life. First of all, I developed a new medium, BL agar, for
      culturing intestinal bacteria, and then I discovered that Bifidus bacteria was
      one of the predominant organisms in human adults. This discovery became the basis
      of my research until today. For two years from 1964, I studied abroad in Germany
      and made good friends, to whom I owe an inestimable debt of gratitude. After
      returning to Japan, I discovered a number of rules governing the intestinal
      ecosystem. Thus, a new interdisciplinary field, intestinal bacteriology, was
      established. Subsequently, I discovered the health effects of fermented milks and
      oligosaccharides and proposed "biogenics". I firmly believe that the fruit of
      creation is granted as a result of endeavoring with a pure heart. 

PMID- 24936369
TI  - Comparison of salivary IgA secretion rate collected by the aspiration method and
      swab method.
AB  - Salivary immunoglobulin A (IgA) is used as an immunity marker, as saliva can be
      easily collected, noninvasively with little stress. However, several saliva
      collection methods can be used. Our comparison between samples collected using
      different methods demonstrated that the salivary IgA secretion rate in samples
      collected using an aspiration method was significantly correlated with that in
      samples collected using a swab method. Moreover, the significant circadian
      variation in salivary IgA secretion rate in the aspirated saliva suggested that
      the aspiration method does not suppress salivary IgA secretion rate variability
      compared with the swab method. Therefore, the aspiration method should be
      considered as the preferable saliva collection method. 

PMID- 24936371
TI  - Oral Administration of EC-12 Increases the Baseline Gene Expression of Antiviral
      Cytokine Genes, IFN-gamma and TNF-alpha, in Splenocytes and Mesenteric Lymph Node
      Cells of Weaning Piglets.
AB  - Weaning piglets are continuously exposed to various viruses. The antiviral
      effects of lactic acid bacteria (LAB) have been confirmed mainly in humans and
      mice, while few studies have been conducted in livestock. In this study, we
      evaluated the effect of oral administration of Enterococcus faecalis strain EC-12
      (EC-12) on the gene expressions of antiviral cytokines in weaning piglets.
      Piglets were allocated to the EC-12-administered group (E group) and the no
      treatment control group (C group). The small intestinal tissue, the mesenteric
      lymph node (MLN) cells and the splenocytes were collected from the piglets. The
      tissue and cells were co-cultured with a live vaccine of porcine reproductive
      respiratory syndrome virus, porcine epidemic diarrhea virus or EC-12. After the
      incubation, the gene expressions of IFN-gamma and TNF-alpha in the tissue and
      cells were evaluated. The gene expressions of IFN-gamma in the MLN cells and TNF
      alpha in the splenocytes were significantly higher in the E group than in the C
      group. However, the increase in the gene expression of antiviral cytokines was
      observed independently of the antigen treatments. The results of the present
      study suggest that oral administration of EC-12 did not increase the response of
      immune cells to specific viral antigens but increased the baseline gene
      expression of antiviral cytokines. 

PMID- 24936373
TI  - Comparison of the accuracy and mechanism of data mining identification of the
      intestinal microbiota with 7 restriction enzymes.
AB  - The intestinal microbiota compositions of 92 Japanese men were identified
      following consumption of identical meals for 3 days, and collected feces were
      analyzed through terminal restriction fragment length polymorphism. The obtained
      operational taxonomic units (OTUs) and subjects' smoking and drinking habits,
      which had 2 nominal partitions, yes or no, were analyzed by Data mining software.
      Identification of subjects for each habit was successfully performed and reported
      previously, but the identification accuracy was closely dependent on the species
      of the applied restriction enzymes for PCR. For the sake of better selection of
      enzymes and understanding the mechanisms of Data mining analysis, 516f-BslI and
      516f-HaeIII, 27f-MspI and 27f-AluI and 35f-HhaI, 35f-MspI and 35f-AluI,
      altogether 7 enzymes, were examined comparatively. Data mining analysis provides
      a Decision tree for identification of subjects and their dividing pathways that
      is produced using a limited number of OTUs, which affects the accuracy of the
      results. The present report discusses not only a global comparison of accuracies
      for characteristics, but also the detailed mechanisms that result in better or
      worse results and the practical roles and functions of OTUs. The OTU at the 1st
      step of the constructed Decision tree was the most important for any
      identification, and for all cases, the combination of subsequent OTUs, which
      formed later in the Decision tree, was also unignorable. Detailed dividing
      pathways were traced and compared for the 7 enzymes and the future supporting
      ideas were provided for better Data mining analysis of the human intestinal
      microbiota. 

PMID- 24936372
TI  - Identification of Human Intestinal Microbiota of 92 Men by Data Mining for 5
      Characteristics, i.e., Age, BMI, Smoking Habit, Cessation Period of Previous
      Smokers and Drinking Habit.
AB  - The intestinal microbiota compositions of 92 men living in Japan were identified
      following consumption of identical meals for 3 days. Fecal samples were analyzed
      by terminal restriction fragment length polymorphism with 4 primer-restriction
      enzyme systems, and the 120 obtained operational taxonomic units (OTUs) were
      analyzed by Data mining software focusing on the following 5 characteristics,
      namely, age, body mass index, present smoking habit, cessation period of previous
      smokers and drinking habit, according to the answers of the subjects. After
      performing Data mining analyses with each characteristic, the details of the
      constructed Decision trees precisely identified the subjects or discriminated
      them into various suitable groups. Through the pathways to reach the groups,
      practical roles of the related OTUs and their quantities were clearly recognized.
      Compared with the other identification methods for OTUs such as bicluster
      analyses, correlation coefficients and principal component analyses, the clear
      difference of this Data mining technique was that it set aside most OTUs and
      emphasized only some closely related ones. For example for a selected
      characteristic, such as smoking habit, only 7 OTUs out of 120 were able to
      identify all smokers, and the remaining 113 OTUs were thought of as data noise
      for smoking. Data mining analyses were affirmed as an effective method of subject
      discrimination for various physiological constitutions. The species of bacteria
      that were closely related to heavy smokers, i.e., HaeIII-291, were also
      discussed. 

PMID- 24936374
TI  - Slower Fermentation Rate of Potato Starch Relative to High-amylose Cornstarch
      Contributes to the Higher Proportion of Cecal Butyrate in Rats.
AB  - This study aimed to examine the mechanism for differential effects of low- (LPPS)
      and high-phosphorus (HPPS) potato starches and high-amylose cornstarch (HACS) on
      rat cecal fermentation, the n-butyrate proportion in particular. In
      ileorectostomized rats, the in vivo resistant starch (RS) contents were
      determined to be 66% (LPPS), 66% (HPPS) and 36% (HACS), but the
      carbohydrate/nitrogen (C/N) ratios of the ileal digesta were comparable among the
      respective starch diets. In intact rats fed diets including similar amounts of
      RS, the cecal n-butyrate proportions in the LPPS- and HPPS-fed rats were equally
      higher than in the HACS-fed rats. The cecal starch contents were fivefold greater
      in the LPPS- and HPPS-fed rats than in the HACS-fed rats. The results suggest
      that potato starches and HACS are not equivalent n-butyrate producers in the rat
      cecum and that the slower fermentation rate of potato starches relative to HACS
      might be responsible for the higher n-butyrate proportion. 

PMID- 24936375
TI  - Difference in Degradation Patterns on Inulin-type Fructans among Strains of
      Lactobacillus delbrueckii and Lactobacillus paracasei.
AB  - Lactobacillus delbrueckii strains were assessed for their degradation patterns of
      various carbohydrates with specific reference to inulin-type fructans in
      comparison with those of Lactobacillus paracasei strains. Firstly, growth curves
      on glucose, fructose, sucrose and inulin-type fructans with increasing degrees of
      fructose polymerization (i.e., 1-kestose, fructo-oligosaccharides and inulin) of
      the strains were compared. L. paracasei DSM 20020 grew well on all these sugars,
      while the growth rates of the 4 L. delbrueckii strains were markedly higher on
      the fructans with a greater degree of polymerization than on fructose and
      sucrose. Secondly, sugar compositions of spent cultures of the strains of L.
      delbrueckii and L. paracasei grown in mMRS containing either the fructans or
      inulin were determined by thin layer chromatography, in which the spent cultures
      of L. paracasei DSM 20020 showed spots of short fructose and sucrose fractions,
      whereas those of the L. delbrueckii strains did not show such spots at all. These
      results suggest that, unlike the L. paracasei strains, the L. delbrueckii strains
      do not degrade the inulin-type fructans extracellularly, but transport the
      fructans capable of greater polymerization preferentially into their cells to be
      degraded intracellularly for their growth. 

PMID- 24936376
TI  - Comparison of Yacon (Smallanthus sonchifolius) Tuber with Commercialized Fructo
      oligosaccharides (FOS) in Terms of Physiology, Fermentation Products and
      Intestinal Microbial Communities in Rats.
AB  - The yacon (Smallanthus sonchifolius) tuber was examined with regard to its
      prebiotic effects compared with commercialized fructo-oligosaccharides (FOS). A
      feed containing 10% yacon tuber, which is equivalent to 5% commercialized FOS in
      terms of the amount of fructo-oligosaccharides (GF2, GF3 and GF4), was
      administrated to rats for 28 days. The yacon diet changed the intestinal
      microbial communities beginning in the first week, resulting in a twofold greater
      concentration of cecal short-chain fatty acids (SCFAs). The SCFA composition
      differed, but the cecal pH in rats fed yacon tuber was equal to that in rats fed
      FOS. Serum triglycerides were lower in rats fed yacon compared with rats fed FOS
      and the control diet. Cecal size was greater with the yacon tuber diet compared
      with the control diet. The abundant fermentation in the intestines created a
      selective environment for the intestinal microbiota, which included Lactobacillus
      acidophilus, Bifidobacterium pseudolongum, Bifidobacterium animalis and
      Barnesiella spp. according to identification with culture-independent analysis,
      16S rRNA gene PCR-DGGE combined with cloning and sequencing. Barnesiella spp. and
      B. pseudolongum were only found in the rats fed the yacon diet, while L.
      acidophilus and B. animalis were found in abundance in rats fed both the yacon
      and FOS diets. The genus Barnesiella has not previously been reported to be
      associated with yacon or FOS fermentation. We concluded that the physiological
      and microbiological effects of the yacon tuber were different from those of FOS.
      Differences in cecal size, blood triglycerides and microbial community profiles
      including their metabolites (SCFAs) between the yacon tuber and FOS were shown to
      be more greatly affected by the yacon tuber rather than FOS. 

PMID- 24936377
TI  - Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial
      Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect.
AB  - Bifidobacterium breve MCC-117 is able to significantly reduce the expression of
      inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to
      improve IL-10 levels in CD4(+)CD25(high) Foxp3(+) lymphocytes in response to heat
      stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular
      patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705
      was significantly lower than that observed for the MCC-117 strain. Considering
      the different capacities of the two bifidobacterium strains to activate toll-like
      receptor (TLR)-2 and their differential immunoregulatory activities in PIE and
      immune cells, we hypothesized that comparative studies with both strains could
      provide important information regarding the molecular mechanism(s) involved in
      the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated
      that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex
      interaction of multiple negative regulators of TLRs as well as inhibition of
      multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable
      ETEC PAMP-induced NF-kappaB, p38 MAPK and PI3 K activation and expression of pro
      inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve
      MCC-117 may activate TLR2 synergistically and cooperatively with one or more
      other pattern recognition receptors (PRRs), and that interactions may result in a
      coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and
      SIGIRR. Upregulation of these negative regulators could have an important
      physiological impact on maintaining or reestablishing homeostatic TLR signals in
      PIE cells. Therefore, in the present study, we gained insight into the molecular
      mechanisms involved in the immunoregulatory effect of B. breve MCC-117. 

PMID- 24936379
TI  - Identification and characterization of lactic Acid bacteria in a commercial
      probiotic culture.
AB  - The aim of the present study was to describe the identification and
      characterization (physiological properties) of two strains of lactic acid
      bacteria (LAB 18 and 48) present in a commercial probiotic culture, FloraMax((r))
      B11. Isolates were characterized morphologically, and identified biochemically.
      In addition, the MIDI System ID, the Biolog ID System, and 16S rRNA sequence
      analyses for identification of LAB 18 and LAB 48 strains were used to compare the
      identification results. Tolerance and resistance to acidic pH, high osmotic
      concentration of NaCl, and bile salts were tested in broth medium. In vitro
      assessment of antimicrobial activity against enteropathogenic bacteria and
      susceptibility to antibiotics were also tested. The results obtained in this
      study showed tolerance of LAB 18 and LAB 48 to pH 3.0, 6.5% NaCl and a high bile
      salt concentration (0.6%). Both strains evaluated showed in vitro antibacterial
      activity against Salmonella enterica serovar Enteritidis, Escherichia coli
      (O157:H7), and Campylobacter jejuni. These are important characteristics of
      lactic acid bacteria that should be evaluated when selecting strains to be used
      as probiotics. Antimicrobial activity of these effective isolates may contribute
      to efficacy, possibly by direct antimicrobial activity in vivo. 

PMID- 24936381
TI  - Food Allergen-induced IgE Response Mouse Model Created by Injection of in vitro
      Differentiated Th2 Cell Culture and Oral Antigen Intake.
AB  - Immunoglobulin (Ig) E is a mediator of food allergic reaction; however, the
      mechanisms of its production in response to an ingested antigen are not fully
      understood. For analysis of IgE production, here we propose an IgE response mouse
      model created by injection of a Th2 cell culture and feeding of an egg white
      diet. According to this manipulation, total and ovalbumin specific IgE production
      were elevated in this model. We think our model enables us to analyze IgE
      induction by Th2 cells in food allergy and can contribute to the development of a
      treatment for food allergy. 

PMID- 24936378
TI  - Phenotypic and genotypic characterization of some lactic Acid bacteria isolated
      from bee pollen: a preliminary study.
AB  - In the present work, five hundred and sixty-seven isolates of lactic acid
      bacteria were recovered from raw bee pollen grains. All isolates were screened
      for their antagonistic activity against both Gram-positive and Gram-negative
      pathogenic bacteria. Neutralized supernatants of 54 lactic acid bacteria (LAB)
      cultures from 216 active isolates inhibited the growth of indicator bacteria.
      They were phenotypically characterized, based on the fermentation of 39
      carbohydrates. Using the simple matching coefficient and unweighted pair group
      algorithm with arithmetic averages (UPGMA), seven clusters with other two members
      were defined at the 79% similarity level. The following species were
      characterized: Lactobacillus plantarum, Lactobacillus fermentum, Lactococcus
      lactis, Pediococcus acidilactici, Pediococcus pentosaceus, and unidentified
      lactobacilli. Phenotypic characteristics of major and minor clusters were also
      identified. Partial sequencing of the 16S rRNA gene of representative isolates
      from each cluster was performed, and ten strains were assigned to seven species:
      Lactobacillus plantarum, Lactobacillus fermentum, Lactococcus lactis,
      Lactobacillus ingluviei, Pediococcus pentosaceus, Lactobacillus acidipiscis and
      Weissella cibaria. The molecular method used failed to determine the exact
      taxonomic status of BH0900 and AH3133. 

PMID- 24936380
TI  - NADH Oxidase of Streptococcus thermophilus 1131 is Required for the Effective
      Yogurt Fermentation with Lactobacillus delbrueckii subsp. bulgaricus 2038.
AB  - We previously reported that dissolved oxygen (DO) suppresses yogurt fermentation
      with an industrial starter culture composed of Lactobacillus delbrueckii subsp.
      bulgaricus (L. bulgaricus) 2038 and Streptococcus thermophilus 1131, and also
      found that reducing the DO in the medium prior to fermentation (deoxygenated
      fermentation) shortens the fermentation time. In this study, we found that
      deoxygenated fermentation primarily increased the cell number of S. thermophilus
      1131 rather than that of L. bulgaricus 2038, resulting in earlier l-lactate and
      formate accumulation. Measurement of the DO concentration and hydrogen peroxide
      generation in the milk medium suggested that DO is mainly removed by S.
      thermophilus 1131. The results using an H2O-forming NADH oxidase (Nox)-defective
      mutant of S. thermophilus 1131 revealed that Nox is the major oxygen-consuming
      enzyme of the bacterium. Yogurt fermentation with the S. thermophilus Deltanox
      mutant and L. bulgaricus 2038 was significantly slower than with S. thermophilus
      1131 and L. bulgaricus 2038, and the DO concentrations of the mixed culture did
      not decrease to less than 2 mg/kg within 3 hr. These observations suggest that
      Nox of S. thermophilus 1131 contributes greatly to yogurt fermentation,
      presumably by removing the DO in milk. 

PMID- 24936382
TI  - Oral Administration of T Cell Epitope Peptide Inhibits the Systemic IL-4 Response
      Elicited by an Egg-White Diet in a TCR Transgenic Mouse Model.
AB  - Oral immunotherapy with T cell epitope peptides is a promising treatment for food
      allergy. We examined the effect of oral administration of an ovalbumin T cell
      epitope peptide (OVA323-339) in a TCR transgenic mouse model (OVA23-3 mice).
      OVA23-3 mice were fed egg-white diet containing ovalbumin and subsequently orally
      administrated the OVA323-339 peptide. Cytokine measurements revealed that the IL
      4 production of splenic CD4(+) T cells was significantly decreased by feeding the
      OVA323-339 peptide. Our study suggested that oral administration of the OVA323
      339 T cell epitope peptide was capable of inhibiting systemic IL-4 response after
      elicitation of predominant Th2 responses. 

PMID- 24936383
TI  - Comparison of treatment patterns and economic outcomes in metastatic breast
      cancer patients initiated on trastuzumab versus lapatinib: a retrospective
      analysis.
AB  - Few studies have compared treatment patterns, healthcare resource utilization
      (HRU), and costs in patients with metastatic breast cancer (mBC) receiving HER2
      directed therapy. This study evaluated these outcomes in patients receiving
      trastuzumab or lapatinib. Adult women with mBC, who were initiated on trastuzumab
      or lapatinib, on or after March 13, 2007, were selected from the US-based
      PharMetrics(r) Integrated Database (2000-2011). Patients were required to be
      continuously enrolled in their healthcare plan for >=6 months prior to and >=30
      days following trastuzumab or lapatinib initiation. Trastuzumab or lapatinib
      discontinuation rates (defined as a gap >=45 consecutive days) were compared
      using multivariate Cox proportional-hazards models. HRU and monthly healthcare
      cost differences were estimated using multivariate negative binomial regression
      models and generalized linear models, respectively. Among the 643 patients who
      met the inclusion criteria, 381 and 262 patients were included in the trastuzumab
      and lapatinib groups, respectively. The majority of the 262 patients receiving
      lapatinib previously received trastuzumab (N = 171 [65.3%]). After adjustment for
      potential confounders, when compared to trastuzumab patients, lapatinib patients
      had a higher rate of treatment discontinuation (hazard ratio [HR] = 1.57; P <
      0.001), a higher rate of outpatient visits (not treatment administration related)
      (IRR = 1.19; P < 0.004), and a lower rate of medical visits associated with
      treatment administration (IRR = 0.34; P < 0.001). There were no significant
      differences between the two groups in total monthly healthcare costs ($11,920 vs.
      $11,898 for trastuzumab and lapatinib patients, respectively; P = 0.451).
      Findings from our study show that, irrespective of the treatment initiated at
      index date, disease management in patients with mBC is associated with similar
      and substantial healthcare costs. Any differences in specific components of
      healthcare costs were associated with differences in the mode of treatment
      administration. Approximately 50% of all costs were non-drug related, and future
      studies should focus on how these costs may be controlled, regardless of mode of
      treatment administration. 

PMID- 24936384
TI  - Prediction of half-marathon race time in recreational female and male runners.
AB  - Half-marathon running is of high popularity. Recent studies tried to find
      predictor variables for half-marathon race time for recreational female and male
      runners and to present equations to predict race time. The actual equations
      included running speed during training for both women and men as training
      variable but midaxillary skinfold for women and body mass index for men as
      anthropometric variable. An actual study found that percent body fat and running
      speed during training sessions were the best predictor variables for half
      marathon race times in both women and men. The aim of the present study was to
      improve the existing equations to predict half-marathon race time in a larger
      sample of male and female half-marathoners by using percent body fat and running
      speed during training sessions as predictor variables. In a sample of 147 men and
      83 women, multiple linear regression analysis including percent body fat and
      running speed during training units as independent variables and race time as
      dependent variable were performed and an equation was evolved to predict half
      marathon race time. For men, half-marathon race time might be predicted by the
      equation (r(2) = 0.42, adjusted r(2) = 0.41, SE = 13.3) half-marathon race time
      (min) = 142.7 + 1.158 * percent body fat (%) - 5.223 * running speed during
      training (km/h). The predicted race time correlated highly significantly (r =
      0.71, p < 0.0001) to the achieved race time. For women, half-marathon race time
      might be predicted by the equation (r(2) = 0.68, adjusted r(2) = 0.68, SE = 9.8)
      race time (min) = 168.7 + 1.077 * percent body fat (%) - 7.556 * running speed
      during training (km/h). The predicted race time correlated highly significantly
      (r = 0.89, p < 0.0001) to the achieved race time. The coefficients of
      determination of the models were slightly higher than for the existing equations.
      Future studies might include physiological variables to increase the coefficients
      of determination of the models. 

PMID- 24936385
TI  - Integrated analysis of chronic lipotoxicity on muscle metabolism and stress and
      its reversal by antioxidants.
AB  - Apart from elevated glucose, triglyceride and cholesterol, elevated levels of
      serum free-fatty acid (FFA) are observed in diabetic patients. Increased FFA load
      can cause multiple dysregulation which are collectively known as lipotoxicity.
      Impacts of FFA induced lipotoxicity were evaluated on various cellular responses
      of metabolism and stress in skeletal muscle myotubes. Under lipotoxicity,
      oxidative capacity of C2C12 myotubes was reduced and decreased levels ATP and NAD
      were observed. Lipotoxicity augmented non-oxidative disposal of metabolites in
      terms of lactate release, IMTG and ceramide synthesis. Concomitantly, insulin
      resistance was also observed. These impacts were in conjunction with increased
      cellular stress, inflammation, proteolysis and apoptosis. Quenching of
      lipotoxicity mediated oxidative stress by antioxidant reverted its deleterious
      impacts and restored insulin stimulated glucose uptake. In conclusion, the in
      vitro lipotoxicity makes a system which resembles in vivo pathology of muscle as
      seen in diabetic patients and represents an integrated perspective of
      lipotoxicity on various parameters of metabolism and stress. 

PMID- 24936387
TI  - Certain class of higher-dimensional simplicial complexes and universal C (*)
      algebras.
AB  - ABSTRACT: In this article we introduce a universal C (*)-algebras associated to
      certain simplicial flag complexes. We denote it by [Formula: see text]it is a
      subalgebra of the noncommutative n-sphere which introduced by J.Cuntz. We present
      a technical lemma to determine the quotient of the skeleton filtration of a
      general universal C (*)-algebra associated to a simplicial flag complex. We
      examine the K-theory of this algebra. Moreover we prove that any such algebra
      divided by the ideal I 2 is commutative. 2000 AMS: 19 K 46.

PMID- 24936386
TI  - Multivariate statistical models of metabolomic data reveals different metabolite
      distribution patterns in isonitrosoacetophenone-elicited Nicotiana tabacum and
      Sorghum bicolor cells.
AB  - Isonitrosoacetophenone (INAP, 2-keto-2-phenyl-acetaldoxime) is a novel inducer of
      plant defense. Oxime functional groups are rare in natural products, but can
      serve as substrates depending on existing secondary pathways. Changes in the
      metabolomes of sorghum and tobacco cells treated with INAP were investigated and
      chemometric tools and multivariate statistical analysis were used to investigate
      the changes in metabolite distribution patterns resulting from INAP elicitation.
      Liquid chromatography combined with mass spectrometry (UHPLC-MS) supplied unique
      chemical fingerprints that were generated in response to specific metabolomic
      events. Principal component analysis (PCA) together with hierarchical cluster
      analysis (HCA) and Metabolic Trees were used for data visualization. Orthogonal
      projections to latent structures discriminant analysis (OPLS-DA) and shared and
      unique structure (SUS) plots were exploited in parallel to reveal the changes in
      the metabolomes. PCA indicated that the cells responded differentially to INAP
      through changes in the metabolite profiles. Furthermore, HCA and Metabolic Trees
      showed that INAP induced metabolic perturbations in both cell lines and that
      homeostasis was re-established over time. OPLS-DA-based shared and unique
      structure (SUS) plots confirmed the results and revealed differences in the
      metabolites distribution patterns between tobacco and sorghum cells. Chemometric
      analyses of metabolomic data offers insight into changes in metabolism in
      response to chemical elicitation. Although similar, the response in sorghum cells
      was found to be more consistent and well-coordinated when compared to tobacco
      cells, indicative of the differences in secondary metabolism between cyanogenic
      and non-cyanogenic plants for oxime metabolism. 

PMID- 24936388
TI  - Dental status, dental treatment procedures and radiotherapy as risk factors for
      infected osteoradionecrosis (IORN) in patients with oral cancer - a comparison of
      two 10 years' observation periods.
AB  - OBJECTIVES: Dental status, dental treatment procedures and radiotherapy dosage as
      potential risk factors for an infected osteoradionecrosis (IORN) in patients with
      oral cancers: Retrospective evaluation of 204 patients treated in two observation
      periods of approximately ten years each. PATIENTS AND METHODS: In group A, 90
      patients were treated in the years 1993-2003, in group B 114 patients in the
      years 1983-1992 (data in brackets). All patients had histopathologically proven
      squamous cell cancers, mainly UICC stages III and IV. 70% (85%, n.s.) had
      undergone surgery before radiotherapy. All patients were referred to the oral and
      maxillofacial surgeon for dental rehabilitation before further treatment.
      Radiotherapy was performed using a 3D-conformal technique with 4-6MV photons of a
      linear accelerator (Co-60 device up to 1987). The majority of patients were
      treated using conventional fractionation with total doses of 60-70 Gy in daily
      fractions of 2 Gy. Additionally, in group A, hyperfractionation was used applying
      a total dose of 72 Gy in fractions of 1.2 Gy twice daily (time interval > 6
      hours). In group B, a similar schedule was used up to a total dose of 82.8 Gy
      (time interval 4-6 hours). 14 (0) patients had radiochemotherapy simultaneously.
      After therapy, the patients were seen regularly by the radiooncologist and - if
      necessary - by the oral and maxillofacial surgeon. The duration of follow-up was
      3.64 years (5 years, p = 0.004). RESULTS: Before radiotherapy, the dental health
      status was very poor. On average, 21.5 (21.2, n.s.) teeth were missing. Further
      2.04 teeth (2.33, n.s.) were carious, 1.4 (0.3, p = 0.002) destroyed. Extractions
      were necessary in 3.6 teeth (5.8, p = 0.008), conserving treatment in 0.4 (0.1, p
      = 0.008) teeth. After dental treatment, 6.30 (4.8, n.s.) teeth remained. IORN was
      diagnosed after conventionally fractionated radiotherapy in 15% (11%, n.s.),
      after hyperfractionation in 0% (34%, p = 0.01). CONCLUSION: Within more than 20
      years there was no improvement in dental status of oral cancer patients.
      Extensive dental treatment procedures remained necessary. There was an impressive
      reduction of the IORN frequency in patients treated in a hyperfractionated manner
      probably resulting from a dose reduction and an extension of the interfraction
      time.

PMID- 24936389
TI  - Occurrence of Vibrio and Salmonella species in mussels (Mytilus
      galloprovincialis) collected along the Moroccan Atlantic coast.
AB  - This study reports the occurrence of different Vibrio and Salmonella species in
      52 samples of Mytilus galloprovincialis collected from four sites along the
      Atlantic coast between Agadir and Essaouira (Anza, Cap Ghir, Imssouane and
      Essaouira). The level of Escherichia coli (E. coli) was also determined to
      evaluate the degree of microbial pollution in the investigated areas. In this
      study three methods were used : AFNOR NF EN ISO 6579 V08-013 for Salmonella spp.,
      the provisional method routinely used by several laboratories (Institut Pasteur,
      Paris,...) for Vibrio cholerae and Vibrio parahaemolyticus in the seafood, and
      the most probable number method (MPN) using Norm ISO/TS 16649-3 (2005) for E.
      coli. The most frequently isolated Vibrios were Vibrio alginolyticus (90.4% of
      samples), followed by V. cholerae non O1 non O139 (15.4%) and V. parahaemolyticus
      (7.7%). Salmonella spp. was found in 15% of the samples. The number of E. coli
      ranged between 0.2/100 g and 1.8 10(3) /100 g of mussel soft tissues. This study
      indicates the potential sanitary risk associated with the presence of pathogenic
      bacteria in cultivated mussels in the two populous regions of southern Morocco,
      where shellfish production and maritime tourism are important to the local
      economy. 

PMID- 24936390
TI  - Association between the serum concentration of triiodothyronine with components
      of metabolic syndrome, cardiovascular risk, and diet in euthyroid post-menopausal
      women without and with metabolic syndrome.
AB  - PURPOSE: To determine the association between the serum concentration of
      triiodothyronine (T3) with components of metabolic syndrome (MetS),
      cardiovascular risk (CVR), and diet in euthyroid post-menopausal women without
      and with MetS. METHODS: A cross-sectional study was performed in 120 voluntary
      women of an indigenous population from Tlaxcala-Mexico. Euthyroid status was
      assessed measuring the serum concentration of thyrotropin (TSH) and thyroid
      hormones, while that of estradiol was measured to confirm the postmenopausal
      condition. MetS was diagnosed using the American Heart Association/National
      Heart, Lung, and Blood Institute Scientific Statement (AHA/NHLBI) criterion.
      Estimation of CVR was calculated based on the Framingham scale. Diet components
      were evaluated based on survey applications. Correlations, logistic regression
      analyses, ANOVA or Kruskall-Wallis, and chi-square tests were used to determine
      significant differences (P <= 0.05) between women without MetS and women with
      MetS having different serum concentrations of T3. RESULTS: Triiodothyronine was
      positively correlated with insulin but negatively correlated with glucose, high
      density lipoprotein cholesterol (HDL-C), and CVR. Compared to women without MetS,
      women with MetS and low-normal T3 concentration showed a high risk for
      hyperglycemia and moderate/high risk for CVR. In contrast, a high-normal T3
      concentration increased the risk to have a big waist circumference, a high
      concentration of HDL-C, and insulin resistance. Diet analysis showed a high grade
      of malnutrition in women from all groups. The intake of calories was positively
      affected by the T3 concentration, albeit it did not affect the extent of
      malnutrition. CONCLUSIONS: In contrast to concentrations of TSH, total thyroxin
      (T4), and free T4, the concentration of serum T3 was strongly correlated with
      cardio-metabolic variables in euthyroid postmenopausal women. In comparison to
      women without MetS, a high-normal serum concentration of T3 in women with MetS is
      positively associated with reduced glycaemia and CVR but negatively related to
      body mass index (BMI), insulin, insulin resistance, and HDL-C. Although the
      analyzed population had a nutritional deficiency, both calories and iron intake
      were positively affected by the T3 concentration. Our results suggest the
      necessity of health programs monitoring T3 in old people in order to treat
      hyperglycemia, cardio-metabolic components, and the ageing anorexia.

PMID- 24936391
TI  - Geophysical assessments of renewable gas energy compressed in geologic pore
      storage reservoirs.
AB  - Renewable energy resources can indisputably minimize the threat of global warming
      and climate change. However, they are intermittent and need buffer storage to
      bridge the time-gap between production (off peak) and demand peaks. Based on
      geologic and geochemical reasons, the North German Basin has a very large
      capacity for compressed air/gas energy storage CAES in porous saltwater aquifers
      and salt cavities. Replacing pore reservoir brine with CAES causes changes in
      physical properties (elastic moduli, density and electrical properties) and
      justify applications of integrative geophysical methods for monitoring this
      energy storage. Here we apply techniques of the elastic full waveform inversion
      FWI, electric resistivity tomography ERT and gravity to map and quantify a
      gradually saturated gas plume injected in a thin deep saline aquifer within the
      North German Basin. For this subsurface model scenario we generated different
      synthetic data sets without and with adding random noise in order to robust the
      applied techniques for the real field applications. Datasets are inverted by
      posing different constraints on the initial model. Results reveal principally the
      capability of the applied integrative geophysical approach to resolve the CAES
      targets (plume, host reservoir, and cap rock). Constrained inversion models of
      elastic FWI and ERT are even able to recover well the gradual gas desaturation
      with depth. The spatial parameters accurately recovered from each technique are
      applied in the adequate petrophysical equations to yield precise quantifications
      of gas saturations. Resulting models of gas saturations independently determined
      from elastic FWI and ERT techniques are in accordance with each other and with
      the input (true) saturation model. Moreover, the gravity technique show high
      sensitivity to the mass deficit resulting from the gas storage and can resolve
      saturations and temporal saturation changes down to +/-3% after reducing any
      shallow fluctuation such as that of groundwater table. 

PMID- 24936392
TI  - Bimini Islands: a characterization of the two major nursery areas; status and
      perspectives.
AB  - Bimini Islands (Bahamas, 25 degrees 44' N 79 degrees 16' W) are characterized by
      a unique tropical marine environment which provides critical nursery habitats and
      food resources for many important species of ecological and economical value. Two
      areas are particularly important in the function and dynamics of the local marine
      environment: North Sound and South Bimini. Since 1998 the northern part of the
      island has been subject to an intense urbanization process that involves the
      construction of an extensive touristic complex. Over the years this activity has
      radically modified a substantial portion of the land, and part of the underwater
      environment as well, threatening the fragile balance of the North Sound nursery
      ground. Effects on marine habitats and on local species have been reported, and
      although some measures to limit the damage have already been taken, the local
      ecosystem could ultimately suffer from continuation of the construction work on
      the area. In 2010, we performed surveys of both main nursery grounds to assess
      the current ecological status and the main differences between the two areas,
      investigating macrobenthic epifauna abundance, seagrass density and abiotic
      parameters. The results of this study indicate that the ecosystem still appears
      in reasonably healthy condition, although showing some concerning trends. These
      data provide baseline conditions to assess further changes, and possibly to
      support the development of plans for the conservation of the North Sound and
      South Bimini coastal ecosystems. 

PMID- 24936393
TI  - Drivers of conservation and utilization of pineapple genetic resources in Benin.
AB  - Valuation of farmer knowledge has been seen as a route to promote sustainable use
      of plant genetic resources. In pineapple production systems in Benin, inadequate
      knowledge of cultivation practices can lead to a number of inconveniences
      including abandon of some varieties and cultivars. To understand how farmer's
      knowledge and cultivation practices impact the sustainable utilization of
      pineapple genetic resources, we surveyed 177 pineapple farmers in southern Benin.
      We assessed farmers' knowledge and analyzed the relationship between their
      knowledge and factors such as age, education, and locality of provenance.
      Pineapple production system was dominated by men (96% respondents). According to
      farmers, Smooth cayenne is international market-oriented while Sugarloaf mainly
      targets domestic and regional markets. All farmers recognized that Smooth cayenne
      provided more income (USD 5,750/ha) than sugarloaf (USD 3,950/ha) in the
      production systems of southern Benin. The high value of median scores in
      comparison with the range of possible score showed that most farmers agreed and
      shared relatively similar knowledge. Correlation matrix and multiple linear
      regressions showed a significant relationship between farmers' practices and
      their knowledge of the plant; their knowledge of pineapple varieties is based on
      fruits traits. Also, farmer's knowledge was associated with locality of
      provenance. Constraints and options for genetic resources conservation and
      utilization in the pineapple production systems in Southern Benin were discussed
      based on current knowledge. 

PMID- 24936394
TI  - Optimization of CCGT power plant and performance analysis using MATLAB/Simulink
      with actual operational data.
AB  - In the Modern scenario, the naturally available resources for power generation
      are being depleted at an alarming rate; firstly due to wastage of power at
      consumer end, secondly due to inefficiency of various power system components. A
      Combined Cycle Gas Turbine (CCGT) integrates two cycles- Brayton cycle (Gas
      Turbine) and Rankine cycle (Steam Turbine) with the objective of increasing
      overall plant efficiency. This is accomplished by utilising the exhaust of Gas
      Turbine through a waste-heat recovery boiler to run a Steam Turbine. The
      efficiency of a gas turbine which ranges from 28% to 33% can hence be raised to
      about 60% by recovering some of the low grade thermal energy from the exhaust gas
      for steam turbine process. This paper is a study for the modelling of CCGT and
      comparing it with actual operational data. The performance model for CCGT plant
      was developed in MATLAB/Simulink. 

PMID- 24936395
TI  - Post-discharge symptoms following fast-track colonic cancer surgery: a
      phenomenological hermeneutic study.
AB  - OBJECTIVE: To obtain knowledge of patients' experiences of postoperative symptoms
      during the initial two weeks following fast-track colonic cancer surgery. METHOD:
      Semi-structured in-depth interviews with seven colonic cancer patients two weeks
      post hospital discharge. Analysis was performed using a phenomenological
      hermeneutical approach. RESULTS: During the first two weeks after discharge the
      patients experienced unfamiliar symptoms that affected their everyday lives.
      Despite distressing symptoms, they applied a "wait-and-see" strategy, and only
      reacted when symptoms became intolerable. The patients failed to report their
      unfamiliar symptoms during hospital nurse follow-up telephone call. While waiting
      for the final histology patients suffered loss of sleep and chaotic thinking, and
      experienced ambiguity of hoping for the best and expecting the worst. CONCLUSION:
      Although fast-track surgery programmes lead to shorter hospitalisation and
      improved physical performance, post-colonic surgery patients experience various
      symptoms after discharge. Healthcare professionals need to address symptoms that
      might have immediate and long-term consequences on patients' everyday life.
      Follow-up studies are encouraged to explore the patient perspective to identify
      the needs of individual patients after hospital discharge.

PMID- 24936396
TI  - Metabolism of amino acids differs in the brains of Djungarian hamster (P.
      sungorus) and Roborovskii hamster (P. roborovskii).
AB  - Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii) belong
      to the same genus of phodopus. Roborovskii hamster shows high locomotor activity
      and low level of dopamine (DA) in the brain. Administration of L-tyrosine, a
      precursor of DA, decreases locomotor activity in Roborovskii hamsters. However,
      the amino acid metabolism in relation to the hyperactivity is not yet well known.
      In the present study, L- and D-amino acid concentrations in the brain, liver, and
      plasma in Djungarian and Roborovskii hamsters were investigated during day and
      night times to explain the possible difference in hyperactivity between them.
      Most of the examined amino acids were higher in the night time when hamsters are
      active compared to those in day time. L- and D-tyrosine concentrations were
      higher in the liver of Roborovskii hamsters than in Djungarian hamsters.
      Furthermore, brain concentration of D-tyrosine was higher in the Roborovskii than
      in Djungarian hamsters, but no significant difference was observed for L-tyrosine
      concentrations between the two species. These results suggest that the conversion
      of L-tyrosine to D-tyrosine in the brain of Roborovskii hamster may be higher
      than in Djungarian hamster, which may cause low DA concentration and
      hyperactivity in Roborovskii hamster. On the other hand, L- and D-serine, which
      are known as sedative factors, were lower in Roborovskii hamsters than Djungarian
      hamster. These results suggest that species-specific regulation in amino acid
      metabolism may contribute to hyperactivity in Roborovskii hamsters. 

PMID- 24936397
TI  - Early discontinuation of endocrine therapy for breast cancer: who is at risk in
      clinical practice?
AB  - PURPOSE: Despite evidence supporting at least five years of endocrine therapy for
      early breast cancer, many women discontinue therapy early. We investigated the
      impact of initial therapy type and specific comorbidities on discontinuation of
      endocrine therapy in clinical practice. METHODS: We identified women in a
      population-based cohort with a diagnosis of early breast cancer and an incident
      dispensing of anastrozole, letrozole or tamoxifen from 2003-2008 (N = 1531).
      Pharmacy and health service data were used to determine therapy duration,
      treatment for pre-existing and post-initiation comorbidities (anxiety,
      depression, hot flashes, musculoskeletal pain, osteoporosis, vaginal atrophy),
      demographic and other clinical characteristics. Time to discontinuation of
      initial, and any, endocrine therapy was calculated. Cox regression determined the
      association of different characteristics on early discontinuation. RESULTS:
      Initial endocrine therapy continued for a median of 2.2 years and any endocrine
      therapy for 4.8 years. Cumulative probability of discontinuing any therapy was
      17% after one year and 58% by five years. Initial tamoxifen, pre-existing
      musculoskeletal pain and newly-treated anxiety predicted shorter initial therapy
      but not discontinuation of any therapy. Early discontinuation of any therapy was
      associated with newly-treated hot flashes (HR = 2.1, 95% CI = 1.3-3.3), not
      undergoing chemotherapy (HR = 1.4, 95% CI = 1.1-1.8) and not undergoing
      mastectomy (HR = 1.5, 95% CI = 1.2-1.8). CONCLUSIONS: Less than half of women
      completed five years of endocrine therapy. Women at greatest risk of stopping any
      therapy early were those with newly-treated hot flashes, no initial chemotherapy,
      or no initial mastectomy. This suboptimal use means that the reductions in
      recurrence demonstrated in clinical trials may not be realised in practice.

PMID- 24936398
TI  - Concomitant use of tamoxifen and endoxifen in postmenopausal early breast cancer:
      prediction of plasma levels by physiologically-based pharmacokinetic modeling.
AB  - PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance
      in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing
      in patients with impaired CYP2D6 metabolism and/or the application of endoxifen,
      the most potent tamoxifen metabolite, are alternative treatment options. To
      elucidate both strategies comprehensively we used a physiologically-based
      pharmacokinetic (PBPK) modeling approach. METHODS: Firstly simulation of
      increasing tamoxifen dosages was performed by a virtual clinical trial including
      populations of CYP2D6 poor (PM), intermediate (IM) and extensive metabolizers
      (EM) (N = 8,000). Secondly we performed PBPK-simulations under consideration of
      tamoxifen use plus concomitant increasing dosages of endoxifen (N = 7,000).
      RESULTS: Our virtual study demonstrates that dose escalation of tamoxifen in IMs
      resulted in endoxifen steady-state plasma concentrations similar to CYP2D6 EMs
      whereas PMs did not reach EM endoxifen levels. Steady-state plasma concentrations
      of tamoxifen, N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and endoxifen were
      similar in CYP2D6 IMs and PMs versus EMs using once daily dosing of 20 mg
      tamoxifen and concomitant CYP2D6 phenotype-adjusted endoxifen dosing in IMs and
      PMs (1 mg/d and 3 mg/d, respectively). CONCLUSION: In conclusion, we suggest that
      co-administration of endoxifen in tamoxifen treated early breast cancer women
      with impaired CYP2D6 metabolism is a promising alternative to reach plasma
      concentrations comparable to CYP2D6 EM patients.

PMID- 24936399
TI  - DNA-encapsulated magnesium phosphate nanoparticles elicit both humoral and
      cellular immune responses in mice.
AB  - The efficacy of pEGFP (plasmid expressing enhanced green fluorescent protein)
      encapsulated PEGylated (meaning polyethylene glycol coated) magnesium phosphate
      nanoparticles (referred to as MgPi-pEGFP nanoparticles) for the induction of
      immune responses was investigated in a mouse model. MgPi-pEGFP nanoparticles
      induced enhanced serum antibody and antigen-specific T-lymphocyte responses, as
      well as increased IFN-? and IL-12 levels compared to naked pEGFP when
      administered via intravenous, intraperitoneal or intramuscular routes. A
      significant macrophage response, both in size and activity, was also observed
      when mice were immunized with the nanoparticle formulation. The response was
      highly specific for the antigen, as the increase in interaction between
      macrophages and lymphocytes as well as lymphocyte proliferation took place only
      when they were re-stimulated with recombinant green fluorescence protein (rGFP).
      Thus the nanoparticle formulation elicited both humoral as well as cellular
      responses. Cytokine profiling revealed the induction of Th-1 type responses. The
      results suggest DNA-encapsulated magnesium phosphate (MgPi) nanoparticles may
      constitute a safer, more stable and cost-efficient DNA vaccine formulation. 

PMID- 24936400
TI  - Aspergillus nidulans Pmts form heterodimers in all pairwise combinations.
AB  - Eukaryotic protein O-mannosyltransferases (Pmts) are divided into three
      subfamilies (Pmt1, Pmt2, and Pmt4) and activity of Pmts in yeasts and animals
      requires assembly into complexes. In Saccharomyces cerevisiae, Pmt1 and Pmt2 form
      a heteromeric complex and Pmt 4 forms a homomeric complex. The filamentous fungus
      Aspergillus nidulans has three Pmts: PmtA (subfamily 2), PmtB (subfamily 1), and
      PmtC (subfamily 4). In this study we show that A. nidulans Pmts form heteromeric
      complexes in all possible pairwise combinations and that PmtC forms homomeric
      complexes. We also show that MsbA, an ortholog of a Pmt4-modified protein, is not
      modified by PmtC. 

PMID- 24936401
TI  - A case of Candida glabrata severe urinary sepsis successfully treated with
      micafungin.
AB  - Candida glabrata is frequently resistant to fluconazole, and in advanced renal
      failure the safe use of this and other recommended drugs is limited. We report a
      case of a 56 years-old diabetic woman with renal failure and severe urinary
      sepsis from C. glabrata successfully treated with micafungin. 

PMID- 24936402
TI  - Subcutaneous phaeohyphomycosis due to Phialemoniopsis ocularis successfully
      treated by voriconazole.
AB  - We report a case of subcutaneous infection in a 67 year-old Cambodian man who
      presented with a 5-month history of swelling of the right foot. Histopathology
      was compatible with phaeohyphomycosis and the hyphomycete Phialemoniopsis
      ocularis was identified by the means of morphological and molecular techniques.
      The patient responded well to a 6-month oral treatment with voriconazole alone. 

PMID- 24936403
TI  - Malassezia pachydermatis fungemia in a preterm neonate resistant to fluconazole
      and flucytosine.
AB  - A case of Malassezia pachydermatis fungemia in a preterm neonate is described.
      The isolate was identified by rDNA sequencing and was resistant to fluconazole
      and flucytosine. Since M. pachydermatis does not require lipid supplementation
      for growth, it can be misidentified as a Candida species. The report highlights
      M. pachydermatis as a cause of late onset sepsis in preterm neonates and
      emphasizes the need for prior antifungal susceptibility testing. 

PMID- 24936404
TI  - Two missense mutations, E123Q and K151E, identified in the ERG11 allele of an
      azole-resistant isolate of Candida kefyr recovered from a stem cell transplant
      patient for acute myeloid leukemia.
AB  - We report on the first cloning and nucleotide sequencing of an ERG11 allele from
      a clinical isolate of Candida kefyr cross-resistant to azole antifungals. It was
      recovered from a stem cell transplant patient, in an oncohematology unit
      exhibiting unexpected high prevalence of C. kefyr. Two amino acid substitutions
      were identified: K151E, whose role in fluconazole resistance was already
      demonstrated in Candida albicans, and E123Q, a new substitution never described
      so far in azole-resistant Candida yeast. 

PMID- 24936405
TI  - Fludarabine and cyclophosphamide provides a nonmyeloablative alternative
      conditioning regimen with low transplant-related mortality and control of high
      risk disease.
AB  - Non-myeloablative allogeneic transplant (NMAT) has a curative potential for
      patients who are not myeloablative allogeneic transplant (MAT) candidates. We
      report a phase II trial of a NMAT regimen with cyclophosphamide and fludarabine
      in 40 patients; 21 of whom had a prior MAT. Day +100 and 1-year transplant
      related mortality (TRM) post-NMAT were 13% and 34%, respectively. Day +100 and 1
      year Overall/Progression-Free Survival (OS/PFS) were 80%/65% and 43%/25%,
      respectively. OS was higher in patients with KPS>=90 and lower in recipient/donor
      CMV+/- vs. other combinations. FluCy has low TRM and is curative in about 20% of
      high-risk patients. 

PMID- 24936407
TI  - A template-based procedure for determining white matter integrity in the internal
      capsule early after stroke.
AB  - The integrity of descending white matter pathways, measured by fractional
      anisotropy from DW-MRI, is a key prognostic indicator of motor recovery after
      stroke. Barriers to translation of fractional anisotropy measures into routine
      clinical practice include the time required for manually delineating volumes of
      interest (VOIs), and inter-examiner variability in this process. This study
      investigated whether registering and then editing template volumes of interest
      'as required' would improve inter-examiner reliability compared with manual
      delineation, without compromising validity. MRI was performed with 30 sub-acute
      stroke patients with motor deficits (mean NIHSS = 11, range 0-17). Four
      independent examiners manually delineated VOIs for the posterior limbs of the
      internal capsules on T1 images, or edited template VOIs that had been registered
      to the T1 images if they encroached on ventricles or basal ganglia. Fractional
      anisotropy within each VOI and interhemispheric asymmetry were then calculated.
      We found that 13/30 registered template VOIs required editing. Edited template
      VOIs were more spatially similar between examiners than the manually delineated
      VOIs (p = 0.005). Both methods produced similar asymmetry values that correlated
      with clinical scores with near perfect levels of agreement between examiners.
      Contralesional fractional anisotropy correlated with age when edited template
      VOIs were used but not when VOIs were manually delineated. Editing template VOIs
      as required is reliable, increases the validity of fractional anisotropy
      measurements in the posterior limb of the internal capsule, and is less time
      consuming compared to manual delineation. This approach could support the use of
      FA asymmetry measures in routine clinical practice. 

PMID- 24936408
TI  - Data on the safety of repeated MRI in healthy children.
AB  - PURPOSE: To address the question of the safety of MRI for research in normal,
      healthy children. We examined MRI, neurocognitive and biometric data collected in
      a group of healthy, normally developing children who have participated in a 10
      year longitudinal fMRI study. MATERIALS AND METHODS: Thirty-one healthy children
      ranging in age from 5 to 7 years were enrolled between 2000 and 2002 and were
      tested yearly as part of a longitudinal study of normal language development.
      Twenty-eight of these children have completed multiple neuroimaging,
      neurocognitive and biometric exams. These children ranged in age from 5 to 18
      years during the course of the study and were exposed to up to 10 annual MRI
      scans. Linear regression of the IQ (WISC-III) (Wechsler, 1991), executive
      function (BRIEF) (Gioia et al., 2002), and language (OWLS) (Carrow-Woolfolk,
      1995) measures was performed against the number of years of exposure to MRI in
      the study. Body mass index (BMI) (Ogden et al., 2006) was also examined as a
      function of years and compared with normative values. RESULTS: The WISC-III Full
      Scale (FSIQ) in our longitudinal cohort was higher than the average at baseline.
      There was no significant change over time in mean FSIQ p = 0.80, OWLS p = 0.16,
      or BRIEF p = 0.67. Similarly, over 10 years there were no significant changes in
      the Coding subtest of WISC III and height and body mass index did not deviate
      from norms (50th percentile). CONCLUSIONS: Examination of neurocognitive and
      biometric data from a decade-long, longitudinal fMRI study of normal language
      development in this small, longitudinal sample of healthy children in the age
      range of 5 to 18 years, who received up to 10 MRI scans, provides scientific
      evidence to support the belief that MRI poses minimal risk for use in research
      with healthy children.

PMID- 24936406
TI  - Distinct neural signatures of cognitive subtypes of dyslexia with and without
      phonological deficits.
AB  - Developmental dyslexia can be distinguished as different cognitive subtypes with
      and without phonological deficits. However, despite some general agreement on the
      neurobiological basis of dyslexia, the neurofunctional mechanisms underlying
      these cognitive subtypes remain to be identified. The present BOLD fMRI study
      thus aimed at investigating by which distinct and/or shared neural activation
      patterns dyslexia subtypes are characterized. German dyslexic fourth graders with
      and without deficits in phonological awareness and age-matched normal readers
      performed a phonological decision task: does the auditory word contain the
      phoneme/a/? Both dyslexic subtypes showed increased activation in the right
      cerebellum (Lobule IV) compared to controls. Subtype-specific increased
      activation was systematically found for the phonological dyslexics as compared to
      those without this deficit and controls in the left inferior frontal gyrus (area
      44: phonological segmentation), the left SMA (area 6), the left precentral gyrus
      (area 6) and the right insula. Non-phonological dyslexics revealed subtype
      specific increased activation in the left supramarginal gyrus (area PFcm;
      phonological storage) and angular gyrus (area PGp). The study thus provides the
      first direct evidence for the neurobiological grounding of dyslexia subtypes.
      Moreover, the data contribute to a better understanding of the frequently
      encountered heterogeneous neuroimaging results in the field of dyslexia. 

PMID- 24936409
TI  - Error-related functional connectivity of the thalamus in cocaine dependence.
AB  - Error processing is a critical component of cognitive control, an executive
      function that has been widely implicated in substance misuse. In previous studies
      we showed that error related activations of the thalamus predicted relapse to
      drug use in cocaine addicted individuals (Luo et al., 2013). Here, we
      investigated whether the error-related functional connectivity of the thalamus is
      altered in cocaine dependent patients (PCD, n = 54) as compared to
      demographically matched healthy individuals (HC, n = 54). The results of a
      generalized psychophysiological interaction analysis showed negative thalamic
      connectivity with the ventral medial prefrontal cortex (vmPFC), in the area of
      perigenual and subgenual anterior cingulate cortex, in HC but not PCD (p < 0.05,
      corrected, two-sample t test). This difference in functional connectivity was not
      observed for task-residual signals, suggesting that it is specific to task
      related processes during cognitive control. Further, the thalamic-vmPFC
      connectivity is positively correlated with the amount of cocaine use in the prior
      month for female but not for male PCD. These findings add to recent literature
      and provide additional evidence for circuit-level biomarkers of cocaine
      dependence. 

PMID- 24936410
TI  - Atypical sulcal anatomy in young children with autism spectrum disorder.
AB  - Autism spectrum disorder is associated with an altered early brain development.
      However, the specific cortical structure abnormalities underlying this disorder
      remain largely unknown. Nonetheless, atypical cortical folding provides lingering
      evidence of early disruptions in neurodevelopmental processes and identifying
      changes in the geometry of cortical sulci is of primary interest for
      characterizing these structural abnormalities in autism and their evolution over
      the first stages of brain development. Here, we applied state-of-the-art sulcus
      based morphometry methods to a large highly-selective cohort of 73 young male
      children of age spanning from 18 to 108 months. Moreover, such large cohort was
      selected through extensive behavioral assessments and stringent inclusion
      criteria for the group of 59 children with autism. After manual labeling of 59
      different sulci in each hemisphere, we computed multiple shape descriptors for
      each single sulcus element, hereby separating the folding measurement into
      distinct factors such as the length and depth of the sulcus. We demonstrated that
      the central, intraparietal and frontal medial sulci showed a significant and
      consistent pattern of abnormalities across our different geometrical indices. We
      also found that autistic and control children exhibited strikingly different
      relationships between age and structural changes in brain morphology. Lastly, the
      different measures of sulcus shapes were correlated with the CARS and ADOS scores
      that are specific to the autistic pathology and indices of symptom severity.
      Inherently, these structural abnormalities are confined to regions that are
      functionally relevant with respect to cognitive disorders in ASD. In contrast to
      those previously reported in adults, it is very unlikely that these abnormalities
      originate from general compensatory mechanisms unrelated to the primary
      pathology. Rather, they most probably reflect an early disruption on
      developmental trajectory that could be part of the primary pathology. 

PMID- 24936412
TI  - Aberrant network integrity of the inferior frontal cortex in women with anorexia
      nervosa.
AB  - Neuroimaging studies investigating the neural profile of anorexia nervosa (AN)
      have revealed a predominant imbalance between the reward and inhibition systems
      of the brain, which are also hallmark characteristics of the disorder. However,
      little is known whether these changes can also be determined independent of task
      condition, using resting-state functional magnetic resonance imaging, in
      currently ill AN patients. Therefore the aim of our study was to investigate
      resting-state connectivity in AN patients (n = 12) compared to healthy athlete (n
      = 12) and non-athlete (n = 14) controls. For this purpose, we used degree
      centrality to investigate functional connectivity of the whole-brain network and
      then Granger causality to analyze effective connectivity (EC), to understand
      directional aspects of potential alterations. We were able to show that the
      bilateral inferior frontal gyrus (IFG) is a region of special functional
      importance within the whole-brain network, in AN patients, revealing reduced
      functional connectivity compared to both healthy control groups. Furthermore, we
      found decreased EC from the right IFG to the midcingulum and increased EC from
      the bilateral orbitofrontal gyrus to the right IFG. For the left IFG, we only
      observed increased EC from the bilateral insula to the left IFG. These results
      suggest that AN patients have reduced connectivity within the cognitive control
      system of the brain and increased connectivity within regions important for
      salience processing. Due to its fundamental role in inhibitory behavior,
      including motor response, altered integrity of the inferior frontal cortex could
      contribute to hyperactivity in AN. 

PMID- 24936414
TI  - Prediction of stroke thrombolysis outcome using CT brain machine learning.
AB  - A critical decision-step in the emergency treatment of ischemic stroke is whether
      or not to administer thrombolysis - a treatment that can result in good recovery,
      or deterioration due to symptomatic intracranial haemorrhage (SICH). Certain
      imaging features based upon early computerized tomography (CT), in combination
      with clinical variables, have been found to predict SICH, albeit with modest
      accuracy. In this proof-of-concept study, we determine whether machine learning
      of CT images can predict which patients receiving tPA will develop SICH as
      opposed to showing clinical improvement with no haemorrhage. Clinical records and
      CT brains of 116 acute ischemic stroke patients treated with intravenous
      thrombolysis were collected retrospectively (including 16 who developed SICH).
      The sample was split into training (n = 106) and test sets (n = 10), repeatedly
      for 1760 different combinations. CT brain images acted as inputs into a support
      vector machine (SVM), along with clinical severity. Performance of the SVM was
      compared with established prognostication tools (SEDAN and HAT scores; original,
      or after adaptation to our cohort). Predictive performance, assessed as area
      under receiver-operating-characteristic curve (AUC), of the SVM (0.744) compared
      favourably with that of prognostic scores (original and adapted versions: 0.626
      0.720; p < 0.01). The SVM also identified 9 out of 16 SICHs, as opposed to 1-5
      using prognostic scores, assuming a 10% SICH frequency (p < 0.001). In summary,
      machine learning methods applied to acute stroke CT images offer automation, and
      potentially improved performance, for prediction of SICH following thrombolysis.
      Larger-scale cohorts, and incorporation of advanced imaging, should be tested
      with such methods. 

PMID- 24936413
TI  - Striatal disorders dissociate mechanisms of enhanced and impaired response
      selection - Evidence from cognitive neurophysiology and computational modelling.
AB  - Paradoxically enhanced cognitive processes in neurological disorders provide
      vital clues to understanding neural function. However, what determines whether
      the neurological damage is impairing or enhancing is unclear. Here we use the
      performance of patients with two disorders of the striatum to dissociate
      mechanisms underlying cognitive enhancement and impairment resulting from damage
      to the same system. In a two-choice decision task, Huntington's disease patients
      were faster and less error prone than controls, yet a patient with the rare
      condition of benign hereditary chorea (BHC) was both slower and more error prone.
      EEG recordings confirmed significant differences in neural processing between the
      groups. Analysis of a computational model revealed that the common loss of
      connectivity between striatal neurons in BHC and Huntington's disease impairs
      response selection, but the increased sensitivity of NMDA receptors in
      Huntington's disease potentially enhances response selection. Crucially the model
      shows that there is a critical threshold for increased sensitivity: below that
      threshold, impaired response selection results. Our data and model thus predict
      that specific striatal malfunctions can contribute to either impaired or enhanced
      selection, and provide clues to solving the paradox of how Huntington's disease
      can lead to both impaired and enhanced cognitive processes. 

PMID- 24936411
TI  - Associations between white matter microstructure and amyloid burden in
      preclinical Alzheimer's disease: A multimodal imaging investigation.
AB  - Some cognitively healthy individuals develop brain amyloid accumulation,
      suggestive of incipient Alzheimer's disease (AD), but the effect of amyloid on
      other potentially informative imaging modalities, such as Diffusion Tensor
      Imaging (DTI), in characterizing brain changes in preclinical AD requires further
      exploration. In this study, a sample (N = 139, mean age 60.6, range 46 to 71)
      from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort enriched
      for AD risk factors, was recruited for a multimodal imaging investigation that
      included DTI and [C-11]Pittsburgh Compound B (PiB) positron emission tomography
      (PET). Participants were grouped as amyloid positive (Abeta+), amyloid
      indeterminate (Abetai), or amyloid negative (Abeta-) based on the amount and
      pattern of amyloid deposition. Regional voxel-wise analyses of four DTI metrics,
      fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), and
      radial diffusivity (Dr), were performed based on amyloid grouping. Three regions
      of interest (ROIs), the cingulum adjacent to the corpus callosum, hippocampal
      cingulum, and lateral fornix, were selected based on their involvement in the
      early stages of AD. Voxel-wise analysis revealed higher FA among Abeta+ compared
      to Abeta- in all three ROIs and in Abetai compared to Abeta- in the cingulum
      adjacent to the corpus callosum. Follow-up exploratory whole-brain analyses were
      consistent with the ROI findings, revealing multiple regions where higher FA was
      associated with greater amyloid. Lower fronto-lateral gray matter MD was
      associated with higher amyloid burden. Further investigation showed a negative
      correlation between MD and PiB signal, suggesting that Abeta accumulation impairs
      diffusion. Interestingly, these findings in a largely presymptomatic sample are
      in contradistinction to relationships reported in the literature in symptomatic
      disease stages of Mild Cognitive Impairment and AD, which usually show higher MD
      and lower FA. Together with analyses showing that cognitive function in these
      participants is not associated with any of the four DTI metrics, the present
      results suggest an early relationship between PiB and DTI, which may be a
      meaningful indicator of the initiating or compensatory mechanisms of AD prior to
      cognitive decline. 

PMID- 24936415
TI  - Age independently affects myelin integrity as detected by magnetization transfer
      magnetic resonance imaging in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a heterogeneous disorder with a
      progressive course that is difficult to predict on a case-by-case basis. Natural
      history studies of MS have demonstrated that age influences clinical progression
      independent of disease duration. OBJECTIVE: To determine whether age would be
      associated with greater CNS injury as detected by magnetization transfer MRI.
      MATERIALS AND METHODS: Forty MS patients were recruited from out-patient clinics
      into two groups stratified by age but with similar clinical disease duration as
      well as thirteen controls age-matched to the older MS group. Images were
      segmented by automated programs and blinded readers into normal appearing white
      matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions
      (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were
      delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1
      weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as
      well as MTR histogram skew and kurtosis were calculated for each region. RESULTS:
      All MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS
      subjects and controls, as expected and previously reported by several studies,
      but not between MS groups. However, MTR measures in the WML did significantly
      differ between the MS groups, in spite of no significant differences in lesion
      counts and volumes. CONCLUSIONS: Despite matching for clinical disease duration
      and recording no significant WML volume difference, we demonstrated strong MTR
      differences in WMLs between younger and older MS patients. These data suggest
      that aging-related processes modify the tissue response to inflammatory injury
      and its clinical outcome correlates in MS.

PMID- 24936416
TI  - Characterizing the microstructural basis of "unidentified bright objects" in
      neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and
      multi-shell diffusion MRI analysis.
AB  - INTRODUCTION: The histopathological basis of "unidentified bright objects" (UBOs)
      (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in
      neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques
      (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide
      measures relating to microstructural change. We combined these methods and
      present previously unreported data on in vivo UBO microstructure in NF1. METHODS:
      3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter
      UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density
      imaging parameters were calculated within UBO sites and in contralateral normal
      appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24
      UBO-cNAWM pairs. RESULTS: No significant alterations in the myelin water fraction
      and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE
      water was significantly higher in UBOs. UBOs furthermore showed increased axial,
      radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis
      and neurite density index compared to cNAWM. Neurite orientation dispersion and
      isotropic fluid fraction were unaltered. CONCLUSION: Our results suggest that
      demyelination and axonal degeneration are unlikely to be present in UBOs, which
      appear to be mainly caused by a shift towards a higher T2-value of the intra- and
      extracellular water pool. This may arise from altered microstructural
      compartmentalization, and an increase in 'extracellular-like', intracellular
      water, possibly due to intramyelinic edema. These findings confirm the added
      value of combining dMRI and MET2 to characterize the microstructural basis of T2
      hyperintensities in vivo.

PMID- 24936417
TI  - Widespread reductions of white matter integrity in patients with long-term
      remission of Cushing's disease.
AB  - BACKGROUND: Hypercortisolism leads to various physical, psychological and
      cognitive symptoms, which may partly persist after the treatment of Cushing's
      disease. The aim of the present study was to investigate abnormalities in white
      matter integrity in patients with long-term remission of Cushing's disease, and
      their relation with psychological symptoms, cognitive impairment and clinical
      characteristics. METHODS: In patients with long-term remission of Cushing's
      disease (n = 22) and matched healthy controls (n = 22) we examined fractional
      anisotropy (FA) values of white matter in a region-of-interest (ROI; bilateral
      cingulate cingulum, bilateral hippocampal cingulum, bilateral uncinate fasciculus
      and corpus callosum) and the whole brain, using 3 T diffusion tensor imaging
      (DTI) and a tract-based spatial statistics (TBSS) approach. Psychological and
      cognitive functioning were assessed with validated questionnaires and clinical
      severity was assessed using the Cushing's syndrome Severity Index. RESULTS: The
      ROI analysis showed FA reductions in all of the hypothesized regions, with the
      exception of the bilateral hippocampal cingulum, in patients when compared to
      controls. The exploratory whole brain analysis showed multiple regions with lower
      FA values throughout the brain. Patients reported more apathy (p = .003) and more
      depressive symptoms (p < .001), whereas depression symptom severity in the
      patient group was negatively associated with FA in the left uncinate fasciculus
      (p < 0.05). Post-hoc analyses showed increased radial and mean diffusivity in the
      patient group. CONCLUSION: Patients with a history of endogenous hypercortisolism
      in present remission show widespread changes of white matter integrity in the
      brain, with abnormalities in the integrity of the uncinate fasciculus being
      related to the severity of depressive symptoms, suggesting persistent structural
      effects of hypercortisolism.

PMID- 24936418
TI  - Patient-specific connectivity pattern of epileptic network in frontal lobe
      epilepsy.
AB  - There is evidence that focal epilepsy may involve the dysfunction of a brain
      network in addition to the focal region. To delineate the characteristics of this
      epileptic network, we collected EEG/fMRI data from 23 patients with frontal lobe
      epilepsy. For each patient, EEG/fMRI analysis was first performed to determine
      the BOLD response to epileptic spikes. The maximum activation cluster in the
      frontal lobe was then chosen as the seed to identify the epileptic network in
      fMRI data. Functional connectivity analysis seeded at the same region was also
      performed in 63 healthy control subjects. Nine features were used to evaluate the
      differences of epileptic network patterns in three connection levels between
      patients and controls. Compared with control subjects, patients showed overall
      more functional connections between the epileptogenic region and the rest of the
      brain and higher laterality. However, the significantly increased connections
      were located in the neighborhood of the seed, but the connections between the
      seed and remote regions actually decreased. Comparing fMRI runs with interictal
      epileptic discharges (IEDs) and without IEDs, the patient-specific connectivity
      pattern was not changed significantly. These findings regarding patient-specific
      connectivity patterns of epileptic networks in FLE reflect local high
      connectivity and connections with distant regions differing from those of healthy
      controls. Moreover, the difference between the two groups in most features was
      observed in the strictest of the three connection levels. The abnormally high
      connectivity might reflect a predominant attribute of the epileptic network,
      which may facilitate propagation of epileptic activity among regions in the
      network. 

PMID- 24936420
TI  - Biased binomial assessment of cross-validated estimation of classification
      accuracies illustrated in diagnosis predictions.
AB  - Multivariate classification is used in neuroimaging studies to infer brain
      activation or in medical applications to infer diagnosis. Their results are often
      assessed through either a binomial or a permutation test. Here, we simulated
      classification results of generated random data to assess the influence of the
      cross-validation scheme on the significance of results. Distributions built from
      classification of random data with cross-validation did not follow the binomial
      distribution. The binomial test is therefore not adapted. On the contrary, the
      permutation test was unaffected by the cross-validation scheme. The influence of
      the cross-validation was further illustrated on real-data from a brain-computer
      interface experiment in patients with disorders of consciousness and from an fMRI
      study on patients with Parkinson disease. Three out of 16 patients with disorders
      of consciousness had significant accuracy on binomial testing, but only one
      showed significant accuracy using permutation testing. In the fMRI experiment,
      the mental imagery of gait could discriminate significantly between idiopathic
      Parkinson's disease patients and healthy subjects according to the permutation
      test but not according to the binomial test. Hence, binomial testing could lead
      to biased estimation of significance and false positive or negative results. In
      our view, permutation testing is thus recommended for clinical application of
      classification with cross-validation. 

PMID- 24936419
TI  - Gray matter alterations in chronic pain: A network-oriented meta-analytic
      approach.
AB  - Several studies have attempted to characterize morphological brain changes due to
      chronic pain. Although it has repeatedly been suggested that longstanding pain
      induces gray matter modifications, there is still some controversy surrounding
      the direction of the change (increase or decrease in gray matter) and the role of
      psychological and psychiatric comorbidities. In this study, we propose a novel,
      network-oriented, meta-analytic approach to characterize morphological changes in
      chronic pain. We used network decomposition to investigate whether different
      kinds of chronic pain are associated with a common or specific set of altered
      networks. Representational similarity techniques, network decomposition and model
      based clustering were employed: i) to verify the presence of a core set of brain
      areas commonly modified by chronic pain; ii) to investigate the involvement of
      these areas in a large-scale network perspective; iii) to study the relationship
      between altered networks and; iv) to find out whether chronic pain targets
      clusters of areas. Our results showed that chronic pain causes both core and
      pathology-specific gray matter alterations in large-scale networks. Common
      alterations were observed in the prefrontal regions, in the anterior insula,
      cingulate cortex, basal ganglia, thalamus, periaqueductal gray, post- and pre
      central gyri and inferior parietal lobule. We observed that the salience and
      attentional networks were targeted in a very similar way by different chronic
      pain pathologies. Conversely, alterations in the sensorimotor and attention
      circuits were differentially targeted by chronic pain pathologies. Moreover,
      model-based clustering revealed that chronic pain, in line with some
      neurodegenerative diseases, selectively targets some large-scale brain networks.
      Altogether these findings indicate that chronic pain can be better conceived and
      studied in a network perspective. 

PMID- 24936421
TI  - Enhanced subgenual cingulate response to altruistic decisions in remitted major
      depressive disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is associated with functional
      abnormalities in fronto-meso-limbic networks contributing to decision-making,
      affective and reward processing impairments. Such functional disturbances may
      underlie a tendency for enhanced altruism driven by empathy-based guilt observed
      in some patients. However, despite the relevance of altruistic decisions to
      understanding vulnerability, as well as everyday psychosocial functioning, in
      MDD, their functional neuroanatomy is unknown. METHODS: Using a charitable
      donations experiment with fMRI, we compared 14 medication-free participants with
      fully remitted MDD and 15 demographically-matched control participants without
      MDD. RESULTS: Compared with the control group, the remitted MDD group exhibited
      enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for
      charitable donation relative to receiving simple rewards and higher striatum
      activation for both charitable donation and simple reward relative to a low level
      baseline. The groups did not differ in demographics, frequency of donations or
      response times, demonstrating only a difference in neural architecture.
      CONCLUSIONS: We showed that altruistic decisions probe residual sgACC
      hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has
      previously been shown to be associated with guilt which promotes altruistic
      decisions. In contrast, the striatum showed common activation to both simple and
      altruistic rewards and could be involved in the so-called "warm glow" of
      donation. Enhanced neural response in the depression group, in areas previously
      linked to altruistic decisions, supports the hypothesis of a possible association
      between hyper-altruism and depression vulnerability, as shown by recent
      epidemiological studies.

PMID- 24936422
TI  - In vivo axonal transport deficits in a mouse model of fronto-temporal dementia.
AB  - BACKGROUND: Axonal transport is vital for neurons and deficits in this process
      have been previously reported in a few mouse models of Alzheimer's disease prior
      to the appearance of plaques and tangles. However, it remains to be determined
      whether axonal transport is defective prior to the onset of neurodegeneration.
      The rTg4510 mouse, a fronto-temporal dementia and parkinsonism-17 (FTDP-17)
      tauopathy model, over-express tau-P301L mutation found in familial forms of FTDP
      17, in the forebrain driven by the calcium-calmodulin kinase II promoter. This
      mouse model exhibits tau pathology, neurodegeneration in the forebrain, and
      associated behavioral deficits beginning at 4-5 months of age. ANIMAL MODEL:
      rTg4510 transgenic mice were used in these studies. Mice were given 2 MUL of
      MnCl2 in each nostril 1 h prior to Magnetic Resonance Imaging (MRI). Following
      MnCl2 nasal lavage, mice were imaged using Manganese enhanced Magnetic Resonance
      Imaging (MEMRI) Protocol with TE = 8.5 ms, TR = 504 ms, FOV = 3.0 cm, matrix size
      = 128 * 128 * 128, number of cycles = 15 with each cycle taking approximately 2
      min, 9 s, and 24 ms using Paravision software (BrukerBioSpin, Billerica, MA).
      During imaging, body temperature was maintained at 37.0  degrees C using an
      animal heating system (SA Instruments, Stony Brook, NY). DATA ANALYSIS: Resulting
      images were analyzed using Paravision software. Regions of interest (ROI) within
      the olfactory neuronal layer (ONL) and the water phantom consisting of one pixel
      (ONL) and 9 pixels (water) were selected and copied across each of the 15 cycles.
      Signal intensities (SI) of ONL and water phantom ROIs were measured. SI values
      obtained for ONL were then normalized the water phantom SI values. The
      correlation between normalized signal intensity in the ONL and time were assessed
      using Prism (GraphPad Software, San Diego, CA). RESULTS: Using the MEMRI
      technique on 1.5, 3, 5, and 10-month old rTg4510 mice and littermate controls, we
      found significant axonal transport deficits present in the rTg4510 mice beginning
      at 3 months of age in an age-dependent manner. Using linear regression analysis,
      we measured rates of axonal transport at 1.5, 3, 5, and 10 months of age in
      rTg4510 and WT mice. Axonal transport rates were observed in rTg4510 mice at 48%
      of WT levels at 3 months, 40% of WT levels at 5 months, and 30% of WT levels at
      10 months of age. In order to determine the point at which tau appears in the
      cortex, we probed for phosphorylated tau levels, and found that pSer262 is
      present at 3 months of age, not earlier at 1.5 months of age, but observed no
      pathological tau species until 6 months of age, months after the onset of the
      transport deficits. In addition, we saw localization of tau in the ONL at 6
      months of age. DISCUSSION: In our study, we identified the presence of age
      dependent axonal transport deficits beginning at 3 months of age in rTg4510 mice.
      We correlated these deficits at 3 months to the presence of hyperphosphorylated
      tau in the brain and the presence within the olfactory epithelium. We observed
      tau pathology not only in the soma of these neurons but also within the axons and
      processes of these neurons. Our characterization of axonal transport in this
      tauopathy model provides a functional time point that can be used for future
      therapeutic interventions.

PMID- 24936423
TI  - Longitudinal deformation models, spatial regularizations and learning strategies
      to quantify Alzheimer's disease progression.
AB  - In the context of Alzheimer's disease, two challenging issues are (1) the
      characterization of local hippocampal shape changes specific to disease
      progression and (2) the identification of mild-cognitive impairment patients
      likely to convert. In the literature, (1) is usually solved first to detect areas
      potentially related to the disease. These areas are then considered as an input
      to solve (2). As an alternative to this sequential strategy, we investigate the
      use of a classification model using logistic regression to address both issues
      (1) and (2) simultaneously. The classification of the patients therefore does not
      require any a priori definition of the most representative hippocampal areas
      potentially related to the disease, as they are automatically detected. We first
      quantify deformations of patients' hippocampi between two time points using the
      large deformations by diffeomorphisms framework and transport these deformations
      to a common template. Since the deformations are expected to be spatially
      structured, we perform classification combining logistic loss and spatial
      regularization techniques, which have not been explored so far in this context,
      as far as we know. The main contribution of this paper is the comparison of
      regularization techniques enforcing the coefficient maps to be spatially smooth
      (Sobolev), piecewise constant (total variation) or sparse (fused LASSO) with
      standard regularization techniques which do not take into account the spatial
      structure (LASSO, ridge and ElasticNet). On a dataset of 103 patients out of
      ADNI, the techniques using spatial regularizations lead to the best
      classification rates. They also find coherent areas related to the disease
      progression. 

PMID- 24936426
TI  - Individual classification of children with epilepsy using support vector machine
      with multiple indices of diffusion tensor imaging.
AB  - INTRODUCTION: Support vector machines (SVM) have recently been demonstrated to be
      useful for voxel-based MR image classification. In the present study we sought to
      evaluate whether this method is feasible in the classification of childhood
      epilepsy intractability based on diffusion tensor imaging (DTI), with adequate
      accuracy. We applied SVM in conjunction DTI indices of fractional anisotropy
      (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD).
      DTI studies have reported white matter abnormalities in childhood-onset epilepsy,
      but the mechanisms underlying these abnormalities are not well understood. The
      aim of this study was to examine the relationship between epileptic seizures and
      cerebral white matter abnormalities identified by DTI in children with active
      compared to remitted epilepsy utilizing an automated and unsupervised
      classification method. METHODS: The DTI data were tensor-derived indices
      including FA, MD, AD and RD in 49 participants including 20 children with
      epilepsy 5-6 years after seizure onset as compared to healthy controls. To
      determine whether there was normalization of white matter diffusion behavior
      following cessation of seizures and treatment, the epilepsy subjects were grouped
      into those with active versus remitted epilepsy. Group comparisons were
      previously made examining FA, MD and RD via whole-brain tract-based spatial
      statistics (TBSS). The SVM analysis was undertaken with the WEKA software package
      with 10-fold cross validation. Weighted sensitivity, specificity and accuracy
      were measured for all the DTI indices for two classifications: (1) controls vs.
      all children with epilepsy and (2) controls vs. children with remitted epilepsy
      vs. children with active epilepsy. RESULTS: Using TBSS, significant differences
      were identified between controls and all children with epilepsy, between controls
      and children with active epilepsy, and also between the active and remitted
      epilepsy groups. There were no significant differences between the remitted
      epilepsy and controls on any DTI measure. In the SVM analysis, the best predictor
      between controls and all children with epilepsy was MD, with a sensitivity of 90
      100% and a specificity between 96.6 and 100%. For the three-way classification,
      the best results were for FA with 100% sensitivity and specificity. CONCLUSION:
      DTI-based SVM classification appears promising for distinguishing children with
      active epilepsy from either those with remitted epilepsy or controls, and the
      question that arises is whether it will prove useful as a prognostic index of
      seizure remission. While SVM can correctly identify children with active epilepsy
      from other groups' diagnosis, further research is needed to determine the
      efficacy of SVM as a prognostic tool in longitudinal clinical studies.

PMID- 24936427
TI  - Modified human contrast sensitivity function based phase mask for susceptibility
      weighted imaging.
AB  - The aim of the work is to increase the visual information in magnetic resonance
      imaging based susceptibility weighted images. Our approach is to amplify spatial
      frequency information of the phase mask used to increase susceptibility weighting
      using a modified version of the human contrast sensitivity function. Thereby, we
      propose a modified version of the human contrast sensitivity function for use in
      phase mask creation. Comparison with conventional susceptibility-weighted imaging
      was undertaken on a qualitative basis and quantitatively with a number of
      established image quality metrics on ex vivo mouse brain magnetic resonance
      images obtained at 16.4 T at various echo times. Four experts also compared the
      quality of in vivo 1.5 and 3 T human brain magnetic resonance images generated
      with traditional susceptibility weighted imaging and with the new method. We
      found that parameters of the modified human contrast sensitivity function can be
      chosen to improve delineation of structural detail of mouse and human brains.
      Information contained in susceptibility-weighted images generated using the
      modified human contrast sensitivity function based phase mask corresponds to that
      in the conventional method, however the visual range over which it is depicted
      has improved visual perception. Hence, qualitative evaluation of information
      contained in susceptibility-weighted images can be improved by amplifying spatial
      frequencies where human contrast sensitivity is reduced. 

PMID- 24936424
TI  - White matter microstructure in late middle-age: Effects of apolipoprotein E4 and
      parental family history of Alzheimer's disease.
AB  - INTRODUCTION: Little is still known about the effects of risk factors for
      Alzheimer's disease (AD) on white matter microstructure in cognitively healthy
      adults. The purpose of this cross-sectional study was to assess the effect of two
      well-known risk factors for AD, parental family history and APOE4 genotype.
      METHODS: This study included 343 participants from the Wisconsin Registry for
      Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of
      interest analysis was performed on fractional anisotropy maps, in addition to
      mean, radial, and axial diffusivity maps, aligned to a common template space
      using a diffeomorphic, tensor-based registration method. The analysis focused on
      brain regions known to be affected in AD including the corpus callosum, superior
      longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses
      assessed the impact of APOE4, parental family history of AD, age, and sex on
      white matter microstructure in late middle-aged participants (aged 47-76 years).
      RESULTS: Both APOE4 and parental family history were associated with
      microstructural white matter differences. Participants with parental family
      history of AD had higher FA in the genu of the corpus callosum and the superior
      longitudinal fasciculus. We observed an interaction between family history and
      APOE4, where participants who were family history positive but APOE4 negative had
      lower axial diffusivity in the uncinate fasciculus, and participants who were
      both family history positive and APOE4 positive had higher axial diffusivity in
      this region. We also observed an interaction between APOE4 and age, whereby older
      participants (=65 years of age) who were APOE4 carriers, had higher MD in the
      superior longitudinal fasciculus and in the portion of the cingulum bundle
      running adjacent to the cingulate cortex, compared to non-carriers. Older
      participants who were APOE4 carriers also showed higher radial diffusivity in the
      genu compared to non-carriers. Across all participants, age had an effect on FA,
      MD, and axial and radial diffusivities. Sex differences were observed in FA and
      radial diffusivity. CONCLUSION: APOE4 genotype, parental family history of AD,
      age, and sex are all associated with microstructural white matter differences in
      late middle-aged adults. In participants at risk for AD, alterations in diffusion
      characteristics-both expected and unexpected-may represent cellular changes
      occurring at the earliest disease stages, but further work is needed. Higher
      mean, radial, and axial diffusivities were observed in participants who are more
      likely to be experiencing later stage preclinical pathology, including
      participants who were both older and carried APOE4, or who were positive for both
      APOE4 and parental family history of AD.

PMID- 24936425
TI  - Understanding disease processes in multiple sclerosis through magnetic resonance
      imaging studies in animal models.
AB  - There are exciting new advances in multiple sclerosis (MS) resulting in a growing
      understanding of both the complexity of the disorder and the relative involvement
      of grey matter, white matter and inflammation. Increasing need for preclinical
      imaging is anticipated, as animal models provide insights into the
      pathophysiology of the disease. Magnetic resonance (MR) is the key imaging tool
      used to diagnose and to monitor disease progression in MS, and thus will be a
      cornerstone for future research. Although gadolinium-enhancing and T2 lesions on
      MRI have been useful for detecting MS pathology, they are not correlative of
      disability. Therefore, new MRI methods are needed. Such methods require
      validation in animal models. The increasing necessity for MRI of animal models
      makes it critical and timely to understand what research has been conducted in
      this area and what potential there is for use of MRI in preclinical models of MS.
      Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS)
      studies that have been carried out in animal models of MS that focus on
      pathology. We compare the MRI phenotypes of animals and patients and provide
      advice on how best to use animal MR studies to increase our understanding of the
      linkages between MR and pathology in patients. This review describes how MRI
      studies of animal models have been, and will continue to be, used in the ongoing
      effort to understand MS. 

PMID- 24936429
TI  - The reliability of the N400 in single subjects: implications for patients with
      disorders of consciousness.
AB  - Functional neuroimaging assessments of residual cognitive capacities, including
      those that support language, can improve diagnostic and prognostic accuracy in
      patients with disorders of consciousness. Due to the portability and relative
      inexpensiveness of electroencephalography, the N400 event-related potential
      component has been proposed as a clinically valid means to identify preserved
      linguistic function in non-communicative patients. Across three experiments, we
      show that changes in both stimuli and task demands significantly influence the
      probability of detecting statistically significant N400 effects - that is, the
      difference in N400 amplitudes caused by the experimental manipulation. In terms
      of task demands, passively heard linguistic stimuli were significantly less
      likely to elicit N400 effects than task-relevant stimuli. Due to the inability of
      the majority of patients with disorders of consciousness to follow task commands,
      the insensitivity of passive listening would impede the identification of
      residual language abilities even when such abilities exist. In terms of stimuli,
      passively heard normatively associated word pairs produced the highest detection
      rate of N400 effects (50% of the participants), compared with semantically
      similar word pairs (0%) and high-cloze sentences (17%). This result is consistent
      with a prediction error account of N400 magnitude, with highly predictable
      targets leading to smaller N400 waves, and therefore larger N400 effects.
      Overall, our data indicate that non-repeating normatively associated word pairs
      provide the highest probability of detecting single-subject N400s during passive
      listening, and may thereby provide a clinically viable means of assessing
      residual linguistic function. We also show that more liberal analyses may further
      increase the detection-rate, but at the potential cost of increased false alarms.

PMID- 24936428
TI  - Disruption of structure-function coupling in the schizophrenia connectome.
AB  - Neuroimaging studies have demonstrated that the phenomenology of schizophrenia
      maps onto diffuse alterations in large-scale functional and structural brain
      networks. However, the relationship between structural and functional deficits
      remains unclear. To answer this question, patients with established schizophrenia
      and matched healthy controls underwent resting-state functional and diffusion
      weighted imaging. The network-based statistic was used to characterize between
      group differences in whole-brain functional connectivity. Indices of white matter
      integrity were then estimated to assess the structural correlates of the
      functional alterations observed in patients. Finally, group differences in the
      relationship between indices of functional and structural brain connectivity were
      determined. Compared to controls, patients with schizophrenia showed decreased
      functional connectivity and impaired white matter integrity in a distributed
      network encompassing frontal, temporal, thalamic, and striatal regions. In
      controls, strong interregional coupling in neural activity was associated with
      well-myelinated white matter pathways in this network. This correspondence
      between structure and function appeared to be absent in patients with
      schizophrenia. In two additional disrupted functional networks, encompassing
      parietal, occipital, and temporal cortices, the relationship between function and
      structure was not affected. Overall, results from this study highlight the
      importance of considering not only the separable impact of functional and
      structural connectivity deficits on the pathoaetiology of schizophrenia, but also
      the implications of the complex nature of their interaction. More specifically,
      our findings support the core nature of fronto-striatal, fronto-thalamic, and
      fronto-temporal abnormalities in the schizophrenia connectome. 

PMID- 24936430
TI  - Abnormal brain structure in youth who commit homicide.
AB  - BACKGROUND: Violence that leads to homicide results in an extreme financial and
      emotional burden on society. Juveniles who commit homicide are often tried in
      adult court and typically spend the majority of their lives in prison. Despite
      the enormous costs associated with homicidal behavior, there have been no serious
      neuroscientific studies examining youth who commit homicide. METHODS: Here we use
      neuroimaging and voxel-based morphometry to examine brain gray matter in
      incarcerated male adolescents who committed homicide (n = 20) compared with
      incarcerated offenders who did not commit homicide (n = 135). Two additional
      control groups were used to understand further the nature of gray matter
      differences: incarcerated offenders who did not commit homicide matched on
      important demographic and psychometric variables (n = 20) and healthy
      participants from the community (n = 21). RESULTS: Compared with incarcerated
      adolescents who did not commit homicide (n = 135), incarcerated homicide
      offenders had reduced gray matter volumes in the medial and lateral temporal
      lobes, including the hippocampus and posterior insula. Feature selection and
      support vector machine learning classified offenders into the homicide and non
      homicide groups with 81% overall accuracy. CONCLUSIONS: Our results indicate that
      brain structural differences may help identify those at the highest risk for
      committing serious violent offenses.

PMID- 24936431
TI  - Prefrontal responses to digit span memory phases in patients with post-traumatic
      stress disorder (PTSD): a functional near infrared spectroscopy study.
AB  - Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory
      impairments have consistently implicated abnormal activities in the frontal and
      parietal lobes. However, most studies have used block designs and could not
      dissociate the multiple phases of working memory. In this study, the involvement
      of the prefrontal cortex in working memory phases was assessed among veterans
      with PTSD and age-/gender-matched healthy controls. Multichannel functional near
      infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex
      hemodynamic activations during memory of neutral (i.e., not trauma-related)
      forward and backward digit span tasks. An event-related experimental design was
      utilized to dissociate the different phases (i.e., encoding, maintenance and
      retrieval) of working memory. The healthy controls showed robust hemodynamic
      activations during the encoding and retrieval processes. In contrast, the
      veterans with PTSD were found to have activations during the encoding process,
      but followed by distinct deactivations during the retrieval process. The PTSD
      participants, but not the controls, appeared to suppress prefrontal activity
      during memory retrieval. This deactivation was more pronounced in the right
      dorsolateral prefrontal cortex during the retrieval phase. These deactivations in
      PTSD patients might implicate an active inhibition of dorsolateral prefrontal
      neural activity during retrieval of working memory. 

PMID- 24936432
TI  - Developmental differences in higher-order resting-state networks in Autism
      Spectrum Disorder.
AB  - OBJECTIVE: Autism Spectrum Disorder (ASD) has been associated with a complex
      pattern of increases and decreases in resting-state functional connectivity. The
      developmental disconnection hypothesis of ASD poses that shorter connections
      become overly well established with development in this disorder, at the cost of
      long-range connections. Here, we investigated resting-state connectivity in
      relatively young boys with ASD and typically developing children. We hypothesized
      that ASD would be associated with reduced connectivity between networks, and
      increased connectivity within networks, reflecting poorer integration and
      segregation of functional networks in ASD. METHODS: We acquired resting-state
      fMRI from 27 boys with ASD and 29 age- and IQ-matched typically developing boys
      between 6 and 16 years of age. Functional connectivity networks were identified
      using Independent Component Analysis (ICA). Group comparisons were conducted
      using permutation testing, with and without voxel-wise correction for grey matter
      density. RESULTS: We found no between-group differences in within-network
      connectivity. However, we did find reduced functional connectivity between two
      higher-order cognitive networks in ASD. Furthermore, we found an interaction
      effect with age in the DMN: insula connectivity increased with age in ASD,
      whereas it decreased in typically developing children. CONCLUSIONS: These results
      show subtle changes in between network connectivity in relatively young boys with
      ASD. However, the global architecture of resting-state networks appeared to be
      intact. This argues against recent suggestions that changes in connectivity in
      ASD may be the most prominent during development.

PMID- 24936433
TI  - Strategic lacunes and their relationship to cognitive impairment in cerebral
      small vessel disease.
AB  - OBJECTIVES: Lacunes are an important disease feature of cerebral small vessel
      disease (SVD) but their relationship to cognitive impairment is not fully
      understood. To investigate this we determined (1) the relationship between lacune
      count and total lacune volume with cognition, (2) the spatial distribution of
      lacunes and the cognitive impact of lacune location, and (3) the whole brain
      anatomical covariance associated with these strategically located regions of
      lacune damage. METHODS: One hundred and twenty one patients with symptomatic
      lacunar stroke and radiological leukoaraiosis were recruited and multimodal MRI
      and neuropsychological data acquired. Lacunes were mapped semi-automatically and
      their volume calculated. Lacune location was automatically determined by
      projection onto atlases, including an atlas which segments the thalamus based on
      its connectivity to the cortex. Lacune locations were correlated with
      neuropsychological results. Voxel based morphometry was used to create anatomical
      covariance maps for these 'strategic' regions. RESULTS: Lacune number and lacune
      volume were positively associated with worse executive function (number p <
      0.001; volume p < 0.001) and processing speed (number p < 0.001; volume p <
      0.001). Thalamic lacunes, particularly those in regions with connectivity to the
      prefrontal cortex, were associated with impaired processing speed (Bonferroni
      corrected p = 0.016). Regions of associated anatomical covariance included the
      medial prefrontal, orbitofrontal, anterior insular cortex and the striatum.
      CONCLUSION: Lacunes are important predictors of cognitive impairment in SVD. We
      highlight the importance of spatial distribution, particularly of anteromedial
      thalamic lacunes which are associated with impaired information processing speed
      and may mediate cognitive impairment via disruption of connectivity to the
      prefrontal cortex.

PMID- 24936434
TI  - Specific brain morphometric changes in spinal cord injury with and without
      neuropathic pain.
AB  - Why only certain patients develop debilitating pain after spinal chord injury and
      whether structural brain changes are implicated remain unknown. The aim of this
      study was to determine if patients with chronic, neuropathic below-level pain
      have specific cerebral changes compared to those who remain pain-free. Voxel
      based morphometry of high resolution, T1-weighted images was performed on three
      subject groups comprising patients with pain (SCI-P, n = 18), patients without
      pain (SCI-N, n = 12) and age- and sex-matched controls (n = 18). The SCI-P group
      was first compared directly with the SCI-N group and then subsequently with
      controls. Overall, grey and white matter changes dependent on the presence of
      pain were revealed. Significant changes were found within the somatosensory
      cortex and also in corticospinal tracts and visual-processing areas. When the SCI
      P group was directly compared with the SCI-N group, reduced grey matter volume
      was found in the deafferented leg area of the somatosensory cortex bilaterally.
      This region negatively correlated with pain intensity. Relative to controls, grey
      matter in this paracentral primary sensory cortex was decreased in SCI-P but
      conversely increased in SCI-N. When compared with controls, discrepant
      corticospinal tract white matter reductions were found in SCI-P and in SCI-N. In
      the visual cortex, SCI-N showed increased grey matter, whilst the SCI-N showed
      reduced white matter. In conclusion, structural changes in SCI are related to the
      presence and degree of below-level pain and involve but are not limited to the
      sensorimotor cortices. Pain-related structural plasticity may hold clinical
      implications for the prevention and management of refractory neuropathic pain. 

PMID- 24936436
TI  - Redox Biology celebrates its first anniversary with over 100 articles, Listing In
      PubMed and 120,000 downloads with over 230 citations!

PMID- 24936435
TI  - SOD1 oxidation and formation of soluble aggregates in yeast: relevance to
      sporadic ALS development.
AB  - Misfolding and aggregation of copper-zinc superoxide dismutase (Sod1) are
      observed in neurodegenerative diseases such as amyotrophic lateral sclerosis
      (ALS). Mutations in Sod1 lead to familial ALS (FALS), which is a late-onset
      disease. Since oxidative damage to proteins increases with age, it had been
      proposed that oxidation of Sod1 mutants may trigger their misfolding and
      aggregation in FALS. However, over 90% of ALS cases are sporadic (SALS) with no
      obvious genetic component. We hypothesized that oxidation could also trigger the
      misfolding and aggregation of wild-type Sod1 and sought to confirm this in a
      cellular environment. Using quiescent, stationary-phase yeast cells as a model
      for non-dividing motor neurons, we probed for post-translational modification
      (PTM) and aggregation of wild-type Sod1 extracted from these cells. By size
      exclusion chromatography (SEC), we isolated two populations of Sod1 from yeast: a
      low-molecular weight (LMW) fraction that is catalytically active and a
      catalytically inactive, high-molecular weight (HMW) fraction. High-resolution
      mass spectrometric analysis revealed that LMW Sod1 displays no PTMs but HMW Sod1
      is oxidized at Cys146 and His71, two critical residues for the stability and
      folding of the enzyme. HMW Sod1 is also oxidized at His120, a copper ligand,
      which will promote loss of this catalytic metal cofactor essential for SOD
      activity. Monitoring the fluorescence of a Sod1-green-fluorescent-protein fusion
      (Sod1-GFP) extracted from yeast chromosomally expressing this fusion, we find
      that HMW Sod1-GFP levels increase up to 40-fold in old cells. Thus, we speculate
      that increased misfolding and inclusion into soluble aggregates is a consequence
      of elevated oxidative modifications of wild-type Sod1 as cells age. Our
      observations argue that oxidative damage to wild-type Sod1 initiates the protein
      misfolding mechanisms that give rise to SALS.

PMID- 24936437
TI  - Nox4 NADPH oxidase contributes to smooth muscle cell phenotypes associated with
      unstable atherosclerotic plaques.
AB  - Plaque instability associated with acute coronary syndromes results in part from
      apoptosis and senescence of cells within the atherosclerotic (AS) lesion.
      Increased cellular oxidative stress has been proposed to contribute to plaque
      progression and changes in composition, leading to plaque instability. Our
      objective was to examine the role of NADPH oxidase in smooth muscle cell (SMC)
      phenotypes associated with an unstable plaque. Aortae were isolated from pre
      lesion (8 weeks of age) and post-lesion (35 weeks of age) hypercholesterolemic
      mice (ApoE(-/-)/LDLR(-/-), AS), and age-matched normal C57BL/6J mice. We observed
      an age-dependent increase in reactive oxygen species (ROS) in aorta from AS mice,
      with evidence for elevated ROS prior to lesion development. Whereas macrophage
      infiltration was restricted to the lesion, oxidized lipids extended beyond the
      plaque and into the vessel wall. Consistent with these findings, we observed
      dynamic changes in the expression of NADPH oxidases in AS vessels. Specifically,
      Nox1 expression was increased early and decreased with lesion progression, while
      induction of Nox4 was a late event. Nox2 and p22(phox) were elevated throughout
      lesion development. Similar to observations in aortae, SMCs isolated from the
      lesion of AS aortae had decreased Nox1 and increased Nox4 levels as compared to
      SMCs from normal mice. AS SMCs demonstrated increased generation of ROS, cell
      cycle arrest, evidence of senescence, and increased susceptibility to apoptosis.
      Overexpression of Nox4 in normal SMCs recapitulated the phenotypes of the AS
      SMCs. We conclude that increased expression of Nox4 in AS may drive SMC
      phenotypes that lead to the plaque instability and rupture responsible for
      myocardial infarction and stroke.

PMID- 24936438
TI  - Thiol-reactivity of the fungicide maneb.
AB  - Maneb (MB) is a manganese-containing ethylene bis-dithiocarbamate fungicide that
      is implicated as an environmental risk factor for Parkinson's disease, especially
      in combination with paraquat (PQ). Dithiocarbamates inhibit aldehyde
      dehydrogenases, but the relationship of this to the combined toxicity of MB + PQ
      is unclear because PQ is an oxidant and MB activates Nrf2 and increases cellular
      GSH without apparent oxidative stress. The present research investigated the
      direct reactivity of MB with protein thiols using recombinant thioredoxin-1
      (Trx1) as a model protein. The results show that MB causes stoichiometric loss of
      protein thiols, reversibly dimerizes the protein and inhibits its enzymatic
      activity. MB reacted at similar rates with low-molecular weight, thiol-containing
      chemicals. Together, the data suggest that MB can potentiate neurotoxicity of
      multiple agents by disrupting protein thiol functions in a manner analogous to
      that caused by oxidative stress, but without GSH depletion.

PMID- 24936439
TI  - A method for assessing mitochondrial bioenergetics in whole white adipose
      tissues.
AB  - Obesity is a primary risk factor for numerous metabolic diseases including
      metabolic syndrome, type II diabetes (T2DM), cardiovascular disease and cancer.
      Although classically viewed as a storage organ, the field of white adipose tissue
      biology is expanding to include the consideration of the tissue as an endocrine
      organ and major contributor to overall metabolism. Given its role in energy
      production, the mitochondrion has long been a focus of study in metabolic
      dysfunction and a link between the organelle and white adipose tissue function is
      likely. Herein, we present a novel method for assessing mitochondrial
      bioenergetics from whole white adipose tissue. This method requires minimal
      manipulation of tissue, and eliminates the need for cell isolation and culture.
      Additionally, this method overcomes some of the limitations to working with
      transformed and/or isolated primary cells and allows for results to be obtained
      more expediently. In addition to the novel method, we present a comprehensive
      statistical analysis of bioenergetic data as well as guidelines for outlier
      analysis. 

PMID- 24936441
TI  - Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent
      hydrogen peroxide consumption.
AB  - Mutations in the DJ-1 gene have been shown to cause a rare autosomal-recessive
      genetic form of Parkinson's disease (PD). The function of DJ-1 and its role in PD
      development has been linked to multiple pathways, however its exact role in the
      development of PD has remained elusive. It is thought that DJ-1 may play a role
      in regulating reactive oxygen species (ROS) formation and overall oxidative
      stress in cells through directly scavenging ROS itself, or through the regulation
      of ROS scavenging systems such as glutathione (GSH) or thioredoxin (Trx) or ROS
      producing complexes such as complex I of the electron transport chain. Previous
      work in this laboratory has demonstrated that isolated brain mitochondria consume
      H2O2 predominantly by the Trx/Thioredoxin Reductase (TrxR)/Peroxiredoxin (Prx)
      system in a respiration dependent manner (Drechsel et al., Journal of Biological
      Chemistry, 2010). Therefore we wanted to determine if mitochondrial H2O2
      consumption was altered in brains from DJ-1 deficient mice (DJ-1(-/-)).
      Surprisingly, DJ-1(-/-) mice showed an increase in mitochondrial respiration
      dependent H2O2 consumption compared to controls. To determine the basis of the
      increased H2O2 consumption in DJ1(-/-) mice, the activities of Trx, Thioredoxin
      Reductase (TrxR), GSH, glutathione disulfide (GSSG) and glutathione reductase
      (GR) were measured. Compared to control mice, brains from DJ-1(-/-) mice showed
      an increase in (1) mitochondrial Trx activity, (2) GSH and GSSG levels and (3)
      mitochondrial glutaredoxin (GRX) activity. Brains from DJ-1(-/-) mice showed a
      decrease in mitochondrial GR activity compared to controls. The increase in the
      enzymatic activities of mitochondrial Trx and total GSH levels may account for
      the increased H2O2 consumption observed in the brain mitochondria in DJ-1(-/-)
      mice perhaps as an adaptive response to chronic DJ-1 deficiency. 

PMID- 24936440
TI  - Oxygen delivery, consumption, and conversion to reactive oxygen species in
      experimental models of diabetic retinopathy.
AB  - Retinal tissue receives its supply of oxygen from two sources - the retinal and
      choroidal circulations. Decreases in retinal blood flow occur in the early stages
      of diabetes, with the eventual development of hypoxia thought to contribute to
      pathological neovascularization. Oxygen consumption in the retina has been found
      to decrease in diabetes, possibly due to either a reduction in neuronal
      metabolism or to cell death. Diabetes also enhances the rate of conversion of
      oxygen to superoxide in the retina, with experimental evidence suggesting that
      mitochondrial superoxide not only drives the overall production of reactive
      oxygen species, but also initiates several pathways leading to retinopathy,
      including the increased activity of the polyol and hexosamine pathways, increased
      production of advanced glycation end products and expression of their receptors,
      and activation of protein kinase C. 

PMID- 24936442
TI  - Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly
      and placental angiodysplasia that leads to recurrent abortion.
AB  - Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were
      infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile
      couples have unexplained infertility. Oxidative stress is associated with male
      and female infertility. However, there is insufficient evidence relating to the
      influence of oxidative stress on the maintenance of a viable pregnancy, including
      pregnancy complications and fetal development. Recently, we have established Tet
      mev-1 conditional transgenic mice, which can express the doxycycline-induced
      mutant SDHC(V69E) transgene and experience mitochondrial respiratory chain
      dysfunction leading to intracellular oxidative stress. In this report, we
      demonstrate that this kind of abnormal mitochondrial respiratory chain-induced
      chronic oxidative stress affects fertility, pregnancy and delivery rates as well
      as causes recurrent abortions, occasionally resulting in maternal death. Despite
      this, spermatogenesis and early embryogenesis are completely normal, indicating
      the mutation's effects to be rather subtle. Female Tet-mev-1 mice exhibit
      thrombocytosis and splenomegaly in both non-pregnant and pregnant mice as well as
      placental angiodysplasia with reduced Flt-1 protein leading to hypoxic
      conditions, which could contribute to placental inflammation and fetal abnormal
      angiogenesis. Collectively these data strongly suggest that chronic oxidative
      stress caused by mitochondrial mutations provokes spontaneous abortions and
      recurrent miscarriage resulting in age-related female infertility. 

PMID- 24936444
TI  - Hyperglycaemia promotes human brain microvascular endothelial cell apoptosis via
      induction of protein kinase C-betaI and prooxidant enzyme NADPH oxidase.
AB  - Blood-brain barrier disruption represents a key feature in hyperglycaemia
      aggravated cerebral damage after an ischaemic stroke. Although the underlying
      mechanisms remain largely unknown, activation of protein kinase C (PKC) is
      thought to play a critical role. This study examined whether apoptosis of human
      brain microvascular endothelial cells (HBMEC) might contribute to hyperglycaemia
      evoked barrier damage and assessed the specific role of PKC in this phenomenon.
      Treatments with hyperglycaemia (25 mM) or phorbol myristate acetate (PMA, a
      protein kinase C activator, 100 nM) significantly increased NADPH oxidase
      activity, O2 (*-) generation, proapoptotic protein Bax expression, TUNEL-positive
      staining and caspase-3/7 activities. Pharmacological inhibition of NADPH oxidase,
      PKC-a, PKC-beta or PKC-betaI via their specific inhibitors and neutralisation of
      O2 (*-) by a cell-permeable superoxide dismutase mimetic, MnTBAP normalised all
      the aforementioned increases induced by hyperglycaemia. Suppression of these PKC
      isoforms also negated the stimulatory effects of hyperglycaemia on the protein
      expression of NADPH oxidase membrane-bound components, Nox2 and p22-phox which
      determine the overall enzymatic activity. Silencing of PKC-betaI gene through use
      of specific siRNAs abolished the effects of both hyperglycaemia and PMA on
      endothelial cell NADPH oxidase activity, O2 (*-) production and apoptosis and
      consequently improved the integrity and function of an in vitro model of human
      cerebral barrier comprising HBMEC, astrocytes and pericytes. Hyperglycaemia
      mediated apoptosis of HBMEC contributes to cerebral barrier dysfunction and is
      modulated by sequential activations of PKC-betaI and NADPH oxidase.

PMID- 24936443
TI  - Oxidative stress and DNA repair and detoxification gene expression in adolescents
      exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily,
      Italy).
AB  - BACKGROUND: The area of Milazzo-Valle del Mela (Sicily, Italy) is considered at
      high risk of environmental crisis by regional authorities. OBJECTIVE: To measure
      oxidative-stress, DNA repair and detoxification genes in school children living
      near the industrial area and in age-matched controls. METHODS: The parent study
      was a biomonitoring investigation evaluating heavy metal urine levels in 226
      children aged 12-14 years, living in the high risk area, and in 29 age-matched
      controls living 45 km far from the industrial site. In the present study 67
      exposed adolescents and 29 controls were included. Samples were analyzed for
      urinary 8-hydroxydeoxyguanosine (8OHdG) levels, and gene expression of OGG1 (DNA
      repair gene), NQO1, ST13, and MT1A (detoxifying genes). RESULTS: Urinary cadmium
      was higher (p = 0.0004) in exposed [geometric mean, 0.46 ug/L; 25th-75th
      percentile: 0.3-0.56] than in control adolescents [geometric mean, 0.26 ug/L;
      25th-75th percentile: 0.2-0.3]. Chromium was also significantly elevated in
      exposed [geometric mean, 1.52 ug/L; 25th-75th percentile: 1.19-1.93] compared
      with controls [geometric mean, 1.25 ug/L; 25th-75th percentile: 1.05-1.48; p =
      0.02]. Urinary 8-OHdG concentration was greater in exposed than in controls
      (71.49 vs 61.87 ug/L, p = 0.02), and it was correlated with cadmium levels (r =
      0.46, p < 0.0001), and with the combined exposure index (r = 0.43, p < 0.0001).
      Moreover, cadmium levels showed a robust correlation with OGG1 and MT1A gene
      expression levels (r = 0.44, p < 0.0001; r = 0.39, p < 0.0001, respectively).
      Finally, OGG1 and MT1A were over-expressed in adolescents from Milazzo-Valle del
      Mela area compared with controls (p = 0.0004; p < 0.0001, respectively).
      CONCLUSIONS: Continuous exposure at relatively low concentrations of heavy metals
      is associated with increased oxidative DNA damage and impaired expression of DNA
      repair and detoxification genes in adolescents.

PMID- 24936445
TI  - Role of Hyaluronic Acid Treatment in the Prevention of Keloid Scarring.
AB  - BACKGROUND: Keloids are benign dermal scars characterized by enhanced growth
      factor signaling, hyperproliferation activity and reduced extracellular matrix
      (ECM) deposition of hyaluronic acid. Our hypothesis is that high molecular weight
      HA can be used to replenish HA deposition in keloids thereby normalizing the
      keloid fibroblast phenotype. METHODS: One normal (NF1) fibroblast culture and
      five keloid (KF1, KF2, KF3, KF4, KF5) fibroblast cultures were analyzed for
      changes in hyperproliferation, growth factor production and extracellular matrix
      deposition following 72 hour treatment with or without 10 MUg/ml HA. RESULTS:
      Proliferation activity decreased significantly in KF3 following HA treatment. Pro
      collagen I expression in KF2 was decreased following HA treatment in association
      with changes in fiber arrangement to more parallel collagen bundles. In addition,
      HA demonstrated a downregulation on TGF-b1 growth factor expression in KF3 and
      KF4 and a decrease in active TGF-b1 release in KF2 and KF5 using ELISA.
      CONCLUSION: Our data demonstrates that HA has the potential to normalize keloid
      fibroblast characteristic features such as hyperproliferation, growth factor
      production and ECM deposition depending on the specific genotype of the keloid
      fibroblast cell line. This study suggests that high molecular weight HA can be
      used to replenish HA deposition in keloid fibroblasts thereby decreasing fibrosis
      and ultimately decreasing keloid manifestation.

PMID- 24936446
TI  - Defining differences among perivascular cells derived from human pluripotent stem
      cells.
AB  - Distinguishing between perivascular cell types remains a hurdle in vascular
      biology due to overlapping marker expressions and similar functionalities.
      Clarifying and defining heterogeneities in vitro among perivascular cells could
      lead to improved cell-based tissue regeneration strategies and a better
      understanding of human developmental processes. We studied contractile vascular
      smooth muscle cells (vSMCs), synthetic vSMCs, and pericytes derived from a common
      human pluripotent stem cell source. Using in vitro cultures, we show unique cell
      morphology, subcellular organelle organization (namely endoplasmic reticulum,
      mitochondria, and stress fibers), and expression of smooth muscle myosin heavy
      chain and elastin for each cell type. While differences in extracellular matrix
      deposition and remodeling were less pronounced, the multipotency, in vivo,
      migratory, invasion, and contractile functionalities are distinctive for each
      cell type. Overall, we define a repertoire of functional phenotypes in vitro
      specific for each of the human perivascular cell types, enabling their study and
      use in basic and translational research.

PMID- 24936447
TI  - THY-1 receptor expression differentiates cardiosphere-derived cells with
      divergent cardiogenic differentiation potential.
AB  - Despite over a decade of intense research, the identity and differentiation
      potential of human adult cardiac progenitor cells (aCPC) remains controversial.
      Cardiospheres have been proposed as a means to expand aCPCs in vitro, but the
      identity of the progenitor cell within these 3D structures is unknown. We show
      that clones derived from cardiospheres could be subdivided based on expression of
      thymocyte differentiation antigen 1 (THY-1/CD90) into two distinct populations
      that exhibit divergent cardiac differentiation potential. One population, which
      is CD90(+), expressed markers consistent with a mesenchymal/myofibroblast cell.
      The second clone type was CD90(-) and could form mature, functional myocytes with
      sarcomeres albeit at a very low rate. These two populations of cardiogenic clones
      displayed distinct cell surface markers and unique transcriptomes. Our study
      suggests that a rare aCPC exists in cardiospheres along with a
      mesenchymal/myofibroblast cell, which demonstrates incomplete cardiac myocyte
      differentiation. 

PMID- 24936448
TI  - Programming and isolation of highly pure physiologically and pharmacologically
      functional sinus-nodal bodies from pluripotent stem cells.
AB  - Therapeutic approaches for "sick sinus syndrome" rely on electrical pacemakers,
      which lack hormone responsiveness and bear hazards such as infection and battery
      failure. These issues may be overcome via "biological pacemakers" derived from
      pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs
      with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based
      antibiotic selection leads to cardiomyocyte aggregates consisting of >80%
      physiologically and pharmacologically functional pacemaker cells. These induced
      sinoatrial bodies (iSABs) exhibited highly increased beating rates (300-400 bpm),
      coming close to those found in mouse hearts, and were able to robustly pace
      myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal
      tissue that is derived from PSCs and may be important for future cell therapies
      and drug testing in vitro. 

PMID- 24936449
TI  - Exosomes as critical agents of cardiac regeneration triggered by cell therapy.
AB  - The CADUCEUS trial of cardiosphere-derived cells (CDCs) has shown that it may be
      possible to regenerate injured heart muscle previously thought to be permanently
      scarred. The mechanisms of benefit are known to be indirect, but the mediators
      have yet to be identified. Here we pinpoint exosomes secreted by human CDCs as
      critical agents of regeneration and cardioprotection. CDC exosomes inhibit
      apoptosis and promote proliferation of cardiomyocytes, while enhancing
      angiogenesis. Injection of exosomes into injured mouse hearts recapitulates the
      regenerative and functional effects produced by CDC transplantation, whereas
      inhibition of exosome production by CDCs blocks those benefits. CDC exosomes
      contain a distinctive complement of microRNAs, with particular enrichment of miR
      146a. Selective administration of a miR-146a mimic reproduces some (but not all)
      of the benefits of CDC exosomes. The findings identify exosomes as key mediators
      of CDC-induced regeneration, while highlighting the potential utility of exosomes
      as cell-free therapeutic candidates. 

PMID- 24936450
TI  - Injury to the spinal cord niche alters the engraftment dynamics of human neural
      stem cells.
AB  - The microenvironment is a critical mediator of stem cell survival, proliferation,
      migration, and differentiation. The majority of preclinical studies involving
      transplantation of neural stem cells (NSCs) into the CNS have focused on injured
      or degenerating microenvironments, leaving a dearth of information as to how NSCs
      differentially respond to intact versus damaged CNS. Furthermore, single,
      terminal histological endpoints predominate, providing limited insight into the
      spatiotemporal dynamics of NSC engraftment and migration. We investigated the
      early and long-term engraftment dynamics of human CNS stem cells propagated as
      neurospheres (hCNS-SCns) following transplantation into uninjured versus
      subacutely injured spinal cords of immunodeficient NOD-scid mice. We
      stereologically quantified engraftment, survival, proliferation, migration, and
      differentiation at 1, 7, 14, 28, and 98 days posttransplantation, and identified
      injury-dependent alterations. Notably, the injured microenvironment decreased
      hCNS-SCns survival, delayed and altered the location of proliferation, influenced
      both total and fate-specific migration, and promoted oligodendrocyte maturation. 

PMID- 24936451
TI  - Cell-state transitions regulated by SLUG are critical for tissue regeneration and
      tumor initiation.
AB  - Perturbations in stem cell activity and differentiation can lead to developmental
      defects and cancer. We use an approach involving a quantitative model of cell
      state transitions in vitro to gain insights into how SLUG/SNAI2, a key
      developmental transcription factor, modulates mammary epithelial stem cell
      activity and differentiation in vivo. In the absence of SLUG, stem cells fail to
      transition into basal progenitor cells, while existing basal progenitor cells
      undergo luminal differentiation; together, these changes result in abnormal
      mammary architecture and defects in tissue function. Furthermore, we show that in
      the absence of SLUG, mammary stem cell activity necessary for tissue regeneration
      and cancer initiation is lost. Mechanistically, SLUG regulates differentiation
      and cellular plasticity by recruiting the chromatin modifier lysine-specific
      demethylase 1 (LSD1) to promoters of lineage-specific genes to repress
      transcription. Together, these results demonstrate that SLUG plays a dual role in
      repressing luminal epithelial differentiation while unlocking stem cell
      transitions necessary for tumorigenesis. 

PMID- 24936452
TI  - Involvement of ER stress in dysmyelination of Pelizaeus-Merzbacher Disease with
      PLP1 missense mutations shown by iPSC-derived oligodendrocytes.
AB  - Pelizaeus-Merzbacher disease (PMD) is a form of X-linked leukodystrophy caused by
      mutations in the proteolipid protein 1 (PLP1) gene. Although PLP1 proteins with
      missense mutations have been shown to accumulate in the rough endoplasmic
      reticulum (ER) in disease model animals and cell lines transfected with mutant
      PLP1 genes, the exact pathogenetic mechanism of PMD has not previously been
      clarified. In this study, we established induced pluripotent stem cells (iPSCs)
      from two PMD patients carrying missense mutation and differentiated them into
      oligodendrocytes in vitro. In the PMD iPSC-derived oligodendrocytes,
      mislocalization of mutant PLP1 proteins to the ER and an association between
      increased susceptibility to ER stress and increased numbers of apoptotic
      oligodendrocytes were observed. Moreover, electron microscopic analysis
      demonstrated drastically reduced myelin formation accompanied by abnormal ER
      morphology. Thus, this study demonstrates the involvement of ER stress in
      pathogenic dysmyelination in the oligodendrocytes of PMD patients with the PLP1
      missense mutation. 

PMID- 24936453
TI  - Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal
      sheets into retinal degenerative mice.
AB  - In this article, we show that mouse embryonic stem cell- or induced pluripotent
      stem cell-derived 3D retinal tissue developed a structured outer nuclear layer
      (ONL) with complete inner and outer segments even in an advanced retinal
      degeneration model (rd1) that lacked ONL. We also observed host-graft synaptic
      connections by immunohistochemistry. This study provides a "proof of concept" for
      retinal sheet transplantation therapy for advanced retinal degenerative diseases.

PMID- 24936454
TI  - 3D In vitro model of a functional epidermal permeability barrier from human
      embryonic stem cells and induced pluripotent stem cells.
AB  - Cornification and epidermal barrier defects are associated with a number of
      clinically diverse skin disorders. However, a suitable in vitro model for
      studying normal barrier function and barrier defects is still lacking. Here, we
      demonstrate the generation of human epidermal equivalents (HEEs) from human
      embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). HEEs are
      structurally similar to native epidermis, with a functional permeability barrier.
      We exposed a pure population of hESC/iPSC-derived keratinocytes, whose
      transcriptome corresponds to the gene signature of normal primary human
      keratinocytes (NHKs), to a sequential high-to-low humidity environment in an
      air/liquid interface culture. The resulting HEEs had all of the cellular strata
      of the human epidermis, with skin barrier properties similar to those of normal
      skin. Such HEEs generated from disease-specific iPSCs will be an invaluable tool
      not only for dissecting molecular mechanisms that lead to epidermal barrier
      defects but also for drug development and screening. 

PMID- 24936456
TI  - Temporal perturbation of the Wnt signaling pathway in the control of cell
      reprogramming is modulated by TCF1.
AB  - Cyclic activation of the Wnt/beta-catenin signaling pathway controls cell fusion
      mediated somatic cell reprogramming. TCFs belong to a family of transcription
      factors that, in complex with beta-catenin, bind and transcriptionally regulate
      Wnt target genes. Here, we show that Wnt/beta-catenin signaling needs to be off
      during the early reprogramming phases of mouse embryonic fibroblasts (MEFs) into
      iPSCs. In MEFs undergoing reprogramming, senescence genes are repressed and
      mesenchymal-to-epithelial transition is favored. This is correlated with a
      repressive activity of TCF1, which contributes to the silencing of Wnt/beta
      catenin signaling at the onset of reprogramming. In contrast, the Wnt pathway
      needs to be active in the late reprogramming phases to achieve successful
      reprogramming. In conclusion, continued activation or inhibition of the Wnt/beta
      catenin signaling pathway is detrimental to the reprogramming of MEFs; instead,
      temporal perturbation of the pathway is essential for efficient reprogramming,
      and the "Wnt-off" state can be considered an early reprogramming marker. 

PMID- 24936455
TI  - SIRT1 is necessary for proficient telomere elongation and genomic stability of
      induced pluripotent stem cells.
AB  - The NAD-dependent deacetylase SIRT1 is involved in chromatin silencing and genome
      stability. Elevated SIRT1 levels in embryonic stem cells also suggest a role for
      SIRT1 in pluripotency. Murine SIRT1 attenuates telomere attrition in vivo and is
      recruited at telomeres in induced pluripotent stem cells (iPSCs). Because
      telomere elongation is an iPSC hallmark, we set out to study the role of SIRT1 in
      pluripotency in the setting of murine embryonic fibroblasts reprogramming into
      iPSCs. We find that SIRT1 is required for efficient postreprogramming telomere
      elongation, and that this effect is mediated by a c-MYC-dependent regulation of
      the mTert gene. We further demonstrate that SIRT1-deficient iPSCs accumulate
      chromosomal aberrations and show a derepression of telomeric heterochromatin.
      Finally, SIRT1-deficient iPSCs form larger teratomas that are poorly
      differentiated, highlighting a role for SIRT1 in exit from pluripotency. In
      summary, this work demonstrates a role for SIRT1 in the maintenance of
      pluripotency and modulation of differentiation. 

PMID- 24936457
TI  - Fine-tuning of iPSC derivation by an inducible reprogramming system at the
      protein level.
AB  - Induced pluripotent stem cells (iPSCs) generated from somatic cells by ectopic
      expression of reprogramming factors, e.g., POU5F1 (OCT4), KLF4, and SOX2, have
      great potential for regenerative medicine. However, before they can be used in a
      clinical setting, the mechanism of reprogramming needs to be better understood.
      Here, by engineering reprogramming factors to a destabilizing protein domain, we
      achieved inducible generation of mouse and pig iPSCs. Stability of the fusion
      protein was precisely regulated by the addition of the cell-permeable small
      molecule trimethoprim (TMP) in a dose-dependent manner. With these tools, we
      found that during the early and middle stages of reprogramming, exogenous OCT4 or
      KLF4 could be omitted, whereas exogenous SOX2 expression at early and middle
      stages was required for successful reprogramming. Our TMP reprogramming system is
      useful for defining the stoichiometry and temporal requirements of transcription
      factors for reprogramming. 

PMID- 24936462
TI  - A trusted voice for stem cell research.

PMID- 24936458
TI  - A 3D sphere culture system containing functional polymers for large-scale human
      pluripotent stem cell production.
AB  - Utilizing human pluripotent stem cells (hPSCs) in cell-based therapy and drug
      discovery requires large-scale cell production. However, scaling up conventional
      adherent cultures presents challenges of maintaining a uniform high quality at
      low cost. In this regard, suspension cultures are a viable alternative, because
      they are scalable and do not require adhesion surfaces. 3D culture systems such
      as bioreactors can be exploited for large-scale production. However, the
      limitations of current suspension culture methods include spontaneous fusion
      between cell aggregates and suboptimal passaging methods by dissociation and
      reaggregation. 3D culture systems that dynamically stir carrier beads or cell
      aggregates should be refined to reduce shearing forces that damage hPSCs. Here,
      we report a simple 3D sphere culture system that incorporates mechanical
      passaging and functional polymers. This setup resolves major problems associated
      with suspension culture methods and dynamic stirring systems and may be optimal
      for applications involving large-scale hPSC production.

PMID- 24936463
TI  - Stepwise differentiation of pluripotent stem cells into osteoblasts using four
      small molecules under serum-free and feeder-free conditions.
AB  - Pluripotent stem cells are a promising tool for mechanistic studies of tissue
      development, drug screening, and cell-based therapies. Here, we report an
      effective and mass-producing strategy for the stepwise differentiation of mouse
      embryonic stem cells (mESCs) and mouse and human induced pluripotent stem cells
      (miPSCs and hiPSCs, respectively) into osteoblasts using four small molecules
      (CHIR99021 [CHIR], cyclopamine [Cyc], smoothened agonist [SAG], and a
      helioxanthin-derivative 4-(4-methoxyphenyl)pyrido[4',3':4,5]thieno[2,3-b]pyridine
      2-carboxamide [TH]) under serum-free and feeder-free conditions. The strategy,
      which consists of mesoderm induction, osteoblast induction, and osteoblast
      maturation phases, significantly induced expressions of osteoblast-related genes
      and proteins in mESCs, miPSCs, and hiPSCs. In addition, when mESCs defective in
      runt-related transcription factor 2 (Runx2), a master regulator of osteogenesis,
      were cultured by the strategy, they molecularly recapitulated osteoblast
      phenotypes of Runx2 null mice. The present strategy will be a platform for
      biological and pathological studies of osteoblast development, screening of bone
      augmentation drugs, and skeletal regeneration. 

PMID- 24936464
TI  - Drosophila perlecan regulates intestinal stem cell activity via cell-matrix
      attachment.
AB  - Stem cells require specialized local microenvironments, termed niches, for normal
      retention, proliferation, and multipotency. Niches are composed of cells together
      with their associated extracellular matrix (ECM). Currently, the roles of ECM in
      regulating niche functions are poorly understood. Here, we demonstrate that
      Perlecan (Pcan), a highly conserved ECM component, controls intestinal stem cell
      (ISC) activities and ISC-ECM attachment in Drosophila adult posterior midgut.
      Loss of Pcan from ISCs, but not other surrounding cells, causes ISCs to detach
      from underlying ECM, lose their identity, and fail to proliferate. These defects
      are not a result of a loss of epidermal growth factor receptor (EGFR) or Janus
      kinase/signal transducer and activator of transcription (JAK/STAT) signaling
      activity but partially depend on integrin signaling activity. We propose that
      Pcan secreted by ISCs confers niche properties to the adjacent ECM that is
      required for ISC maintenance of stem cell identity, activity, and anchorage to
      the niche. 

PMID- 24936465
TI  - Lineage tracing of mammary epithelial cells using cell-type-specific cre
      expressing adenoviruses.
AB  - Lineage tracing using Cre/lox transgenic mice provides a powerful tool for
      studying normal mammary epithelial cell (MEC) development and the cellular
      origins of mammary tumors under physiological settings. However, generation of
      new transgenic mice for lineage-tracing purposes is often time consuming. Here,
      we report a lineage-tracing tool for MECs based on intraductal injection of
      lineage-specific Cre-expressing adenovirus (Ad-Cre). Using well-characterized
      promoters for Keratin 8 and Keratin 14, we generated lineage-specific Ad-Cre
      lines for luminal and basal MECs, respectively. By pulse-chase lineage tracing
      using these Ad-Cre lines, we showed that luminal and basal lineages are largely
      self-sustained and that IRS1 and IRS2 are essential for maintaining the basal
      lineage; we also showed that heterogeneous mammary tumors can be induced from
      luminal MECs in mice carrying the Etv6-NTRK3 fusion gene. Overall, we validated
      the Ad-Cre system as a promising and efficient tool for fate mapping of normal
      and malignant cells in adult tissues. 

PMID- 24936466
TI  - Growth hormone is secreted by normal breast epithelium upon progesterone
      stimulation and increases proliferation of stem/progenitor cells.
AB  - Using in vitro and in vivo experimental systems and in situ analysis, we show
      that growth hormone (GH) is secreted locally by normal human mammary epithelial
      cells upon progesterone stimulation. GH increases proliferation of a subset of
      cells that express growth hormone receptor (GHR) and have functional properties
      of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions,
      an expansion of the cell population that expresses GHR was observed, suggesting
      that GH signaling may contribute to breast cancer development. 

PMID- 24936467
TI  - Bone marrow endosteal mesenchymal progenitors depend on HIF factors for
      maintenance and regulation of hematopoiesis.
AB  - Maintenance and differentiation of hematopoietic stem cells (HSCs) is regulated
      through cell-autonomous and non-cell-autonomous mechanisms within specialized
      bone marrow microenvironments. Recent evidence demonstrates that signaling by HIF
      1alpha contributes to cell-autonomous regulation of HSC maintenance. By
      investigating the role of HIF factors in bone marrow mesenchymal progenitors, we
      found that murine endosteal mesenchymal progenitors express high levels of HIF
      1alpha and HIF-2alpha and proliferate preferentially in hypoxic conditions ex
      vivo. Inactivation of either HIF-1alpha or HIF-2alpha dramatically affects their
      phenotype, propagation, and differentiation. Also, downregulation of HIF factors
      provokes an increase in interferon-responsive genes and triggers expansion and
      differentiation of hematopoietic progenitors by a STAT1-mediated mechanism.
      Interestingly, in conditions of demand-driven hematopoiesis HIF factors are
      specifically downregulated in mesenchymal progenitors in vivo. In conclusion, our
      findings indicate that HIF factors also regulate hematopoiesis non-cell
      autonomously by preventing activation of a latent program in mesenchymal
      progenitors that promotes hematopoiesis. 

PMID- 24936468
TI  - Primitive neural stem cells in the adult mammalian brain give rise to GFAP
      expressing neural stem cells.
AB  - Adult forebrain definitive neural stem cells (NSCs) comprise a subpopulation of
      GFAP-expressing subependymal cells that arise from embryonic fibroblast growth
      factor (FGF)-dependent NSCs that are first isolated from the developing brain at
      E8.5. Embryonic FGF-dependent NSCs are derived from leukemia inhibitory factor
      (LIF)-responsive, Oct4-expressing primitive NSCs (pNSCs) that are first isolated
      at E5.5. We report the presence of a rare population of pNCSs in the
      periventricular region of the adult forebrain. Adult-derived pNSCs (AdpNSCs) are
      GFAP(-), LIF-responsive stem cells that display pNSC properties, including Oct4
      expression and the ability to integrate into the inner cell mass of blastocysts.
      AdpNSCs generate self-renewing, multipotent colonies that give rise to definitive
      GFAP(+) NSCs in vitro and repopulate the subependyma after the ablation of
      GFAP(+) NSCs in vivo. These data support the hypothesis that a rare population of
      pNSCs is present in the adult brain and is upstream of the GFAP(+) NSCs. 

PMID- 24936469
TI  - Human neural precursor cells promote neurologic recovery in a viral model of
      multiple sclerosis.
AB  - Using a viral model of the demyelinating disease multiple sclerosis (MS), we show
      that intraspinal transplantation of human embryonic stem cell-derived neural
      precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs
      were not detectable beyond day 8 posttransplantation. Improved motor skills were
      associated with a reduction in neuroinflammation, decreased demyelination, and
      enhanced remyelination. Evidence indicates that the reduced neuroinflammation is
      correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells
      (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells
      resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs
      acted, in part, through secretion of TGF-beta1 and TGF-beta2. These findings
      indicate that the transient presence of hNPCs transplanted in an animal model of
      MS has powerful immunomodulatory effects and mediates recovery. Further
      investigation of the restorative effects of hNPC transplantation may aid in the
      development of clinically relevant MS treatments. 

PMID- 24936470
TI  - Human intestinal tissue with adult stem cell properties derived from pluripotent
      stem cells.
AB  - Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as
      a source for transplantation therapies and are rapidly becoming valuable tools
      for human disease modeling. However, many applications are limited due to the
      lack of robust differentiation paradigms that allow for the isolation of defined
      functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult
      stem cells from hPSCs that gave rise to functional human intestinal tissue
      comprising all major cell types of the intestine. Histological and functional
      analyses revealed that such human organoid cultures could be derived with high
      purity and with a composition and morphology similar to those of cultures
      obtained from human biopsies. Importantly, hPSC-derived organoids responded to
      the canonical signaling pathways that control self-renewal and differentiation in
      the adult human intestinal stem cell compartment. This adult stem cell system
      provides a platform for studying human intestinal disease in vitro using
      genetically engineered hPSCs. 

PMID- 24936471
TI  - Derivation of traceable and transplantable photoreceptors from mouse embryonic
      stem cells.
AB  - Retinal degenerative diseases resulting in the loss of photoreceptors are one of
      the major causes of blindness. Photoreceptor replacement therapy is a promising
      treatment because the transplantation of retina-derived photoreceptors can be
      applied now to different murine retinopathies to restore visual function. To have
      an unlimited source of photoreceptors, we derived a transgenic embryonic stem
      cell (ESC) line in which the Crx-GFP transgene is expressed in photoreceptors and
      assessed the capacity of a 3D culture protocol to produce integration-competent
      photoreceptors. This culture system allows the production of a large number of
      photoreceptors recapitulating the in vivo development. After transplantation,
      integrated cells showed the typical morphology of mature rods bearing external
      segments and ribbon synapses. We conclude that a 3D protocol coupled with ESCs
      provides a safe and renewable source of photoreceptors displaying a development
      and transplantation competence comparable to photoreceptors from age-matched
      retinas. 

PMID- 24936473
TI  - Single-cell gene expression profiles define self-renewing, pluripotent, and
      lineage primed states of human pluripotent stem cells.
AB  - Pluripotent stem cells display significant heterogeneity in gene expression, but
      whether this diversity is an inherent feature of the pluripotent state remains
      unknown. Single-cell gene expression analysis in cell subsets defined by surface
      antigen expression revealed that human embryonic stem cell cultures exist as a
      continuum of cell states, even under defined conditions that drive self-renewal.
      The majority of the population expressed canonical pluripotency transcription
      factors and could differentiate into derivatives of all three germ layers. A
      minority subpopulation of cells displayed high self-renewal capacity,
      consistently high transcripts for all pluripotency-related genes studied, and no
      lineage priming. This subpopulation was characterized by its expression of a
      particular set of intercellular signaling molecules whose genes shared common
      regulatory features. Our data support a model of an inherently metastable self
      renewing population that gives rise to a continuum of intermediate pluripotent
      states, which ultimately become primed for lineage specification. 

PMID- 24936472
TI  - Genetic and chemical correction of cholesterol accumulation and impaired
      autophagy in hepatic and neural cells derived from Niemann-Pick Type C patient
      specific iPS cells.
AB  - Niemann-Pick type C (NPC) disease is a fatal inherited lipid storage disorder
      causing severe neurodegeneration and liver dysfunction with only limited
      treatment options for patients. Loss of NPC1 function causes defects in
      cholesterol metabolism and has recently been implicated in deregulation of
      autophagy. Here, we report the generation of isogenic pairs of NPC patient
      specific induced pluripotent stem cells (iPSCs) using transcription activator
      like effector nucleases (TALENs). We observed decreased cell viability,
      cholesterol accumulation, and dysfunctional autophagic flux in NPC1-deficient
      human hepatic and neural cells. Genetic correction of a disease-causing mutation
      rescued these defects and directly linked NPC1 protein function to impaired
      cholesterol metabolism and autophagy. Screening for autophagy-inducing compounds
      in disease-affected human cells showed cell type specificity. Carbamazepine was
      found to be cytoprotective and effective in restoring the autophagy defects in
      both NPC1-deficient hepatic and neuronal cells and therefore may be a promising
      treatment option with overall benefit for NPC disease. 

PMID- 24936474
TI  - X Chromosome of female cells shows dynamic changes in status during human somatic
      cell reprogramming.
AB  - Induced pluripotent stem cells (iPSCs) acquire embryonic stem cell (ESC)-like
      epigenetic states, including the X chromosome. Previous studies reported that
      human iPSCs retain the inactive X chromosome of parental cells, or acquire two
      active X chromosomes through reprogramming. Most studies investigated the X
      chromosome states in established human iPSC clones after completion of
      reprogramming. Thus, it is still not fully understood when and how the X
      chromosome reactivation occurs during reprogramming. Here, we report a dynamic
      change in the X chromosome state throughout reprogramming, with an initial robust
      reactivation of the inactive X chromosome followed by an inactivation upon
      generation of nascent iPSC clones. iPSCs with two active X chromosomes or an
      eroded X chromosome arise in passaging iPSCs. These data provide important
      insights into the plasticity of the X chromosome of human female iPSCs and will
      be crucial for the future application of such cells in cell therapy and X-linked
      disease modeling. 

PMID- 24936475
TI  - Heterochromatin dynamics during the differentiation process revealed by the DNA
      methylation reporter mouse, MethylRO.
AB  - In mammals, DNA is methylated at CpG sites, which play pivotal roles in gene
      silencing and chromatin organization. Furthermore, DNA methylation undergoes
      dynamic changes during development, differentiation, and in pathological
      processes. The conventional methods represent snapshots; therefore, the dynamics
      of this marker within living organisms remains unclear. To track this dynamics,
      we made a knockin mouse that expresses a red fluorescent protein (RFP)-fused
      methyl-CpG-binding domain (MBD) protein from the ROSA26 locus ubiquitously; we
      named it MethylRO (methylation probe in ROSA26 locus). Using this mouse, we
      performed RFP-mediated methylated DNA immunoprecipitation sequencing (MeDIP-seq),
      whole-body section analysis, and live-cell imaging. We discovered that mobility
      and pattern of heterochromatin as well as DNA methylation signal intensity inside
      the nuclei can be markers for cellular differentiation status. Thus, the MethylRO
      mouse represents a powerful bioresource and technique for DNA methylation
      dynamics studies in developmental biology, stem cell biology, as well as in
      disease states. 

PMID- 24936477
TI  - Tumor-associated macrophages contribute to tumor progression in ovarian cancer.
AB  - Ovarian cancer is the leading cause of death in women with gynecological
      malignancy and improvements in current treatments are needed. As with many other
      solid cancers, the ovarian tumor microenvironment is emerging as a key player in
      tumor progression and a potential therapeutic target. The tumor microenvironment
      contains several non-malignant cell types that are known to contribute to tumor
      progression and metastasis. Included in this population of non-malignant cells
      are several different types of immune cells, of which tumor-associated
      macrophages (TAMs) are the most abundant. An increasing amount of evidence is
      emerging to suggest that TAMs display a unique activation profile in ovarian
      tumors and are able to create an immunosuppressive microenvironment, allowing
      tumors to evade immune detection and promoting tumor progression. Therefore, an
      increased understanding of how these immune cells interact with tumor cells and
      the microenvironment will greatly benefit the development of more effective
      immunotherapies to treat ovarian cancer. This review focuses on the role of TAMs
      in the ovarian tumor microenvironment and how they promote tumor progression. 

PMID- 24936476
TI  - FOXN1 (GFP/w) reporter hESCs enable identification of integrin-beta4, HLA-DR, and
      EpCAM as markers of human PSC-derived FOXN1(+) thymic epithelial progenitors.
AB  - Thymic epithelial cells (TECs) play a critical role in T cell maturation and
      tolerance induction. The generation of TECs from in vitro differentiation of
      human pluripotent stem cells (PSCs) provides a platform on which to study the
      mechanisms of this interaction and has implications for immune reconstitution. To
      facilitate analysis of PSC-derived TECs, we generated hESC reporter lines in
      which sequences encoding GFP were targeted to FOXN1, a gene required for TEC
      development. Using this FOXN1 (GFP/w) line as a readout, we developed a
      reproducible protocol for generating FOXN1-GFP(+) thymic endoderm cells.
      Transcriptional profiling and flow cytometry identified integrin-beta4 (ITGB4,
      CD104) and HLA-DR as markers that could be used in combination with EpCAM to
      selectively purify FOXN1(+) TEC progenitors from differentiating cultures of
      unmanipulated PSCs. Human FOXN1(+) TEC progenitors generated from PSCs facilitate
      the study of thymus biology and are a valuable resource for future applications
      in regenerative medicine. 

PMID- 24936478
TI  - Local perspectives of the ability of HIA stakeholder engagement to capture and
      reflect factors that impact Alaska Native health.
AB  - BACKGROUND: Health impact assessment (HIA) is a process used to inform planning
      and decision making in a range of sectors by identifying potential positive and
      negative health effects of proposed projects, programs, or policies. Stakeholder
      engagement is an integral component of HIA and requires careful consideration of
      participant diversity and appropriate methodologies. Ensuring that the engagement
      process is able to capture and address Indigenous worldviews and definitions of
      health is important where Indigenous populations are impacted, particularly in
      northern regions experiencing increases in natural resource development
      activities on Indigenous lands. OBJECTIVE: Investigate local participant
      perspectives of an HIA of a proposed Alaska coal mine, with a focus on the
      ability of the HIA process to capture, reflect, and address health concerns
      communicated by Alaska Native participants. DESIGN: A qualitative approach guided
      by semi-structured interviews with purposeful sampling to select key informants
      who participated in the coal mine HIA stakeholder engagement process. RESULTS:
      QUALITATIVE DATA IDENTIFIED THREE KEY THEMES AS IMPORTANT FROM THE PERSPECTIVE OF
      ALASKA NATIVE PARTICIPANTS IN THE ALASKA COAL MINE HIA STAKEHOLDER ENGAGEMENT
      PROCESS: (i) the inability of the engagement process to recognize an Indigenous
      way of sharing or gathering information; (ii) the lack of recognizing traditional
      knowledge and its use for identifying health impacts and status; and (iii) the
      inability of the engagement process to register the relationship Indigenous
      people have with the environment in which they live. Issues of trust in the HIA
      process and of the HIA findings were expressed within each theme. CONCLUSIONS:
      Recommendations derived from the research identify the need to acknowledge and
      incorporate the history of colonialism and assimilation policies in an HIA when
      assessing health impacts of resource development on or near Indigenous lands.
      These historical contexts must be included in baseline conditions to understand
      particular vulnerabilities and potential health risks and impacts. Further, HIA
      practitioners should recognize the range of definitions for "health" and
      demonstrate this recognition throughout the stakeholder engagement process, as
      well as in the HIA recommendations and suggested mitigations.

PMID- 24936479
TI  - The Correlation between Echocardiographic Findings and QT Interval in Cirrhotic
      Patients.
AB  - BACKGROUND: Although many electrocardiographic abnormalities have been reported
      previously, prolonged QTC interval represented as the most important ECG finding
      in patients with liver cirrhosis. Echocardiography can detect structural cardiac
      abnormalities in cirrhotic patients. OBJECTIVES: The present study aimed to
      determine the correlation between QTC prolongation and echocardiographic findings
      in end stage liver cirrhosis. METHODS: The present study was conducted on 100
      patients selected through convenient sampling. We recruited 80 cirrhotic patients
      with CHILD score > B or MELD score > 15 from the transplantation ward of Nemazee
      educational hospital. A complete echocardiographic study, including chamber
      quantification, a complete flow Doppler, and tissue Doppler analysis, was
      performed for each patient using a GE vivid 3 system equipped with Tissue Doppler
      Imaging (TDI). Then, twelve-lead ECG was carried out and QTc interval was
      calculated in all patients. The data were analyzed using the SPSS statistical
      software (v. 13) and Pearson's correlation coefficient. P value < 0.05 was
      considered statistically significant. RESULTS: The patients' age ranged from 20
      to 60 years old and 62.5% of them were male. According to the results, the only
      parameter which was significantly associated with prolonged QTc interval was Left
      Ventricular End Diastolic Dimension (LVEDD). Additionally, a linear direct
      relationship was found between corrected QT interval and LVEDD (r = 0.41, P <
      0.001). CONCLUSIONS: The current study showed a positive correlation between QTC
      prolongation as an electerocardiographic finding and LVEDD in echocardiography of
      the cirrhotic patients. This may indicate a direct relationship between the
      electrophysiological problems and the severity of volume overload in cirrhotic
      patients.

PMID- 24936481
TI  - The Effects of 6 Isocaloric Meals on Body Weight, Lipid Profiles, Leptin, and
      Adiponectin in Overweight Subjects (BMI > 25).
AB  - BACKGROUND: It seems that meal frequency is negatively related to body weight,
      but the relationship between meal frequency and weight loss is not clearly known
      yet. OBJECTIVES: The present study aimed to investigate whether 6 isocaloric
      meals affected body weight, lipid profiles, leptin, and adiponectin in overweight
      subjects. METHODS: The present randomized controlled trial was conducted on 90
      overweight subjects in 3 months. The subjects were randomly divided into two
      groups. The control group continued their normal diet, while the intervention
      group was required to follow a 6 isocaloric meal diet instead of their previous
      meal pattern (3 meals and 2 snacks). The planned reduced calorie diets for both
      groups were identical, except for meal pattern. Blood samples were analyzed prior
      to and at the end of the study for total cholesterol, triglyceride, HDL-C, LDL-C,
      leptin, and adiponectinn concentrations. Paired t-test was used for comparison of
      the measurements before and after the study in each group. Besides, independent t
      test was used for comparison of the measurements between the groups. P value less
      than 0.05 was considered as statistically significant. RESULTS: The mean age of
      the participants was 36.38 +/- 9.7 in the intervention group and 37.6 +/- 10.9 in
      the control group. In comparison to the control group, the intervention group
      showed a significant decrease in total cholesterol (P < 0.001), LDL-C (P <
      0.001), BMI (P < 0.001), triglyceride (P < 0.001), and leptin (P = 0.002) and a
      significant increase in HDL (P < 0.001) and adiponectin (P = 0.031). CONCLUSIONS:
      The 6 isocaloric meal pattern led to a reduction in BMI, lipid profiles (total
      cholesterol, LDL-C, triglyceride), and leptin concentrations and an increase in
      HDL and adiponectin compared to the normal diet.

PMID- 24936480
TI  - Additive Effects of Anxiety and Depression on Body Mass Index among Blacks: Role
      of Ethnicity and Gender.
AB  - BACKGROUND: Most studies on mental health associates of obesity have focused on
      depression and less is known about the role of anxiety in obesity. OBJECTIVES:
      This study compared the additive effects of General Anxiety Disorder (GAD) and
      Major Depressive Disorder (MDD) on Body Mass Index (BMI) across sub-populations
      of Blacks based on the intersection of ethnicity and gender. METHODS: Data came
      from the National Survey of American Life (NSAL), 2001 - 2003. The participants
      consisted of 3,570 African Americans and 1,621 Caribbean Blacks. Twelve-month MDD
      and GAD were determined using the World Mental Health Composite International
      Diagnostic Interview (CIDI). Levels of BMI were categorized based on being equal
      to or larger than 25, 30, 35, and 40 kg/m(2). We fitted linear regression models
      specific for our groups, which were defined based on the intersection of
      ethnicity and gender. Additionally, age, education, marital status, employment,
      and region were controlled. RESULTS: Among Caribbean Black men and African
      American women, lifetime GAD, but not MDD, was associated with high BMI. Among
      Caribbean Black women, lifetime MDD, but not GAD, was associated with high BMI.
      CONCLUSIONS: Intersection of ethnicity and gender may determine how anxiety and
      depression are associated with BMI among Blacks. Sub-populations of Blacks (e.g.
      based on ethnicity and gender) may have specific mental health determinants or
      consequences of obesity. Future research should investigate how and why the
      additive effects of anxiety and depression on obesity vary across ethnic and
      gender groups of Blacks.

PMID- 24936483
TI  - Efficacy and safety of beating heart mitral valve replacement.
AB  - BACKGROUND: The interest in beating heart surgery is growing since better results
      can be obtained with this procedure compared to conventional myocardial
      protection techniques using cardioplegic solutions. This led us to consider
      mitral valve replacement with beating heart. OBJECTIVES: This study aimed to
      determine the safety and efficacy of beating heart mitral valve replacement
      without cross clamp. METHODS: This prospective study was conducted on the
      patients with isolated mitral valve disease requiring mitral valve replacement
      according to ACC / AHA guidelines. In this study, 15 patients underwent mitral
      valve replacement using beating heart technique (Group A) and 15 ones underwent
      mitral valve replacement using arrested heart technique (Group B). The patients
      were randomized using block randomization. The data were analyzed using the SPSS
      statistical software. RESULTS: Preoperative parameters were comparable in the two
      groups. Most of the patients in both study groups were in NYHA class III or IV.
      Postoperatively, however, most of the patients in the two groups were either in
      NYHA class I or II. No mortality occurred in the beating heart group, while one
      mortality occurred in the arrested heart group. The results showed a significant
      difference between the two groups regarding the mean bypass time, mean operating
      time, mean ICU stay, and mean length of hospital stay. CONCLUSIONS: Beating heart
      mitral valve replacement is equally safe as the arrested heart technique. Thus,
      it is recommended as an appropriate alternative to the arrested heart technique
      for mitral valve replacement.

PMID- 24936482
TI  - The surgical outcome of anomalous origin of the left coronary artery from the
      pulmonary artery.
AB  - BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary
      artery (ALCAPA) is a rare congenital anomaly which represents one of the most
      common causes of myocardial ischemia and infarction in children. This anomaly, if
      left untreated, results in a very high mortality rate within the first year of
      life. Yet, immediate surgical correction can lead to excellent results.
      OBJECTIVES: The present study aimed to determine the surgical outcome of ALCAPA.
      METHODS: This study was conducted on 53 patients with ALCAPA operated from
      January 2005 to December 2012. Surgical repair was carried out as soon as the
      diagnosis was made. Surgery was thus undertaken on an urgent basis (within 48
      hours) in the patients with congestive heart failure or critical clinical status
      and on a semi- elective basis (within a few days) in the remaining children.
      Operations for all the patients were performed through a median sternotomy using
      established standard cardiopulmonary bypass technique. Grouped variables were
      compared using chi-square test with Yates' correction. Besides, McNemar's test
      was used to assess the relationship between preoperative ejection fraction and
      mitral incompetence. All the analyses were performed using the SPSS statistical
      software, version 11.5 (SPSS Inc., Chicago, IL). RESULTS: The patients' median
      age at presentation was 4 months. The mean preoperative ejection fraction was
      36.5%. The results showed a significant relationship between age at presentation
      and impairment of ejection fraction (P < 0.001). At first, 23% of our patients
      presented with ejection fraction < 35%. However, 6 months after the operation,
      the ejection fraction improved to a mean of 53.07% (SD = 8.5) ranging from 38 -
      66%. There were 5 postoperative hospital deaths with an overall mortality rate of
      9.6%. CONCLUSIONS: Excellent results with desirable long-term outcomes can be
      achieved in the infants with ALCAPA using coronary artery implantation
      techniques. The best potential for recovery of the left ventricular function is
      in younger symptomatic infants despite the worst initial presentation.
      Normalization of cardiac function is expected within the first year in all
      operative survivors with a patent dual coronary system.

PMID- 24936485
TI  - Inadvertent implantation of pacemaker lead in the left ventricle: kill two birds
      with one stone.
AB  - We report an asymptomatic patient in whom the intravenous pacemaker (PM) lead was
      inadvertently implanted in LV through the perforated interventricular septum. He
      had no embolic events during the last 9 years after the implantation. Possible
      explanation of the uncomplicated follow-up period is that the patient had been
      taking warfarin because of mechanical mitral valve prosthesis. 

PMID- 24936484
TI  - Generator and lead-related complications of implantable cardioverter
      defibrillators.
AB  - BACKGROUND: Increase in the number of patients treated with Implantable
      Cardioverter Defibrillator (ICD) requests more attention regarding its
      complications. OBJECTIVES: This study aimed to assess the generator- and lead
      related complications at implantation and during follow-up in the patients who
      were treated with ICD for primary and secondary prevention reasons. METHODS: We
      retrospectively reviewed 255 consecutive patients who underwent transvenous ICD
      implantation for the first time in a 7-year period and were followed-up for 3
      years at Tehran Heart Center. The personal and clinical data of the patients as
      well as specific data on the ICD implantation were retrieved. The frequency of
      each of the complications was reported and the study variables were compared
      between the patients with and without complications using Student's t-test and
      chi-square test where appropriate. P values less than 0.05 were considered as
      statistically significant. RESULTS: Out of a total of 525 implanted leads and 255
      implanted devices in 255 patients (mean age = 62.57 +/- 13.50 years; male = 196
      [76.9%]), complications leading to generator or lead replacement occurred in 32
      patients (12.5%). The results revealed no significant difference between the
      patients with and without complications regarding gender and age (P = 0.206 and P
      = 0.824, respectively). Also, no significant difference was found between the two
      groups concerning the ejection fraction (P = 0.271). Lead fracture was the most
      frequent lead-related complication and was observed in 17 patients (6.6%).
      Besides, it was mainly observed in the RV leads. Generator-related complications
      leading to generator replacement were observed in 2 patients (0.7%). CONCLUSIONS:
      Despite considerable improvements in the ICD technology, the rate of the ICD
      complications leading to device replacement and surgical revision, especially
      those related to the leads, is still clinically important.

PMID- 24936486
TI  - Ruptured valsalva sinus aneurysm to pericardium simulated aortic root dissection.
AB  - Ruptured valsalva sinus aneurysm to pericardium is a rare condition. Here, we
      described a case presented with tamponade. Initially, hemopericardium was
      partially drained and then, imaging evaluations were done. Transesophageal
      echocardiography showed limited dissection of aortic sinus and CT angiography of
      the ascending aorta showed deformed dilated right coronary sinus. Besides,
      surgery showed that windsock tract of the right coronary sinus had ruptured into
      the pericardium with avulsed right coronary aortic cusp. This case indicated a
      rare cause of cardiac tamponade and insufficiency of imaging modalities for
      making an accurate diagnosis. 

PMID- 24936487
TI  - ULTRASONOGRAPHY: a new beginning with international open access.

PMID- 24936488
TI  - Another step toward the global ultrasound community.

PMID- 24936490
TI  - General principles of carotid Doppler ultrasonography.
AB  - Carotid Doppler ultrasonography is a popular tool for evaluating atherosclerosis
      of the carotid artery. Its two-dimensional gray scale can be used for measuring
      the intima-media thickness, which is very good biomarker for atherosclerosis and
      can aid in plaque characterization. The plaque morphology is related to the risk
      of stroke. The ulceration of plaque is also known as one of the strong predictors
      of future embolic event risk. Color Doppler ultrasonography and pulse Doppler
      ultrasonography have been used for detecting carotid artery stenosis. Doppler
      ultrasonography has unique physical properties. The operator should be familiar
      with the physics and other parameters of Doppler ultrasonography to perform
      optimal Doppler ultrasonography studies. 

PMID- 24936489
TI  - Practice guideline for the performance of breast ultrasound elastography.
AB  - Ultrasound (US) elastography is a valuable imaging technique for tissue
      characterization. Two main types of elastography, strain and shear-wave, are
      commonly used to image breast tissue. The use of elastography is expected to
      increase, particularly with the increased use of US for breast screening.
      Recently, the US elastographic features of breast masses have been incorporated
      into the 2nd edition of the Breast Imaging Reporting and Data System (BI-RADS) US
      lexicon as associated findings. This review suggests practical guidelines for
      breast US elastography in consensus with the Korean Breast Elastography Study
      Group, which was formed in August 2013 to perform a multicenter prospective study
      on the use of elastography for US breast screening. This article is focused on
      the role of elastography in combination with B-mode US for the evaluation of
      breast masses. Practical tips for adequate data acquisition and the
      interpretation of elastography results are also presented. 

PMID- 24936491
TI  - Early quantification of the therapeutic efficacy of the vascular disrupting
      agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2
      liver tumors.
AB  - PURPOSE: To evaluate the usefulness of dynamic contrast-enhanced ultrasonography
      (DCE-US) in the early quantification of hemodynamic change following
      administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2
      liver tumor model. METHODS: This study was approved by our institutional animal
      care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with
      intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2,
      4, 6, and 24 hours following their treatment. The tumor perfusion parameters were
      obtained from the time-intensity curve of the DCE-US data. Repeated measures
      analysis of variance was performed to assess any significant change in tumor
      perfusion over time. Relative changes in the DCE-US parameters between the
      baseline and follow-up assessments were correlated with the relative changes in
      tumor size over the course of seven days using Pearson correlation. RESULTS: CKD
      516 treatment resulted in significant changes in the DCE-US parameters, including
      the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC
      during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed
      that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up
      were significantly lower than the baseline values (P<0.05). However, none of
      early changes in the DCE-US parameters until 24-hour follow-up showed a
      significant correlation with the relative changes in tumor size during seven days
      after CKD-516 treatment. CONCLUSION: Our results suggest that a novel VDA (CKD
      516) can cause disruption of tumor perfusion as early as two hours after
      treatment and that the therapeutic effect of CKD-516 treatment can be effectively
      quantified using DCE-US.

PMID- 24936492
TI  - Usefulness of acoustic radiation force impulse elastography in the differential
      diagnosis of benign and malignant solid pancreatic lesions.
AB  - PURPOSE: The aim of this study was to evaluate the tissue stiffness of solid
      pancreatic lesions by using acoustic radiation force impulse (ARFI) elastography
      to differentiate benign from malignant pancreatic lesions. METHODS: ARFI
      elastography was performed in 26 patients who had 27 focal solid pancreatic
      lesions, including 8 benign lesions (mass-forming pancreatitis, 5; autoimmune
      pancreatitis, 3) and 19 malignant lesions (pancreatic adenocarcinoma, 16;
      metastasis from colorectal cancer, 2; malignant neuroendocrine tumor, 1). On the
      elastographic images of virtual touch tissue imaging (VTI), the echogenicity of
      the mass was categorized on a 5-grade scale. On the elastographic image of
      virtual touch tissue quantification (VTQ), the shear wave velocities (SWVs) of
      the lesion and surrounding parenchyma were measured. RESULTS: On the VTI images,
      the mean echogenicity score of the malignant lesions (3.7+/-1.0) was higher than
      that of the benign lesions (3.1+/-0.4; P=0.023). On the VTQ images, there were no
      statistical differences in the mean SWV between the benign (2.4+/-1.1 m/sec) and
      malignant (3.3+/-1.0 m/sec) lesions (P=0.101). However, the mean SWV difference
      values between the lesion and background parenchyma of the malignant lesions
      (1.5+/-0.8 m/sec) were higher than those of the benign lesions (0.4+/-0.3 m/sec;
      P=0.011). CONCLUSION: ARFI elastography can determine the relative stiffness
      between a lesion and the background pancreatic parenchyma using VTI and VTQ,
      which is helpful in the differentiation between benign and malignant solid
      pancreatic lesions.

PMID- 24936493
TI  - Shear-wave elastography for breast masses: local shear wave speed (m/sec) versus
      Young modulus (kPa).
AB  - PURPOSE: To evaluate and compare the performance of shear-wave elastography (SWE)
      for breast masses using the local shear wave speed (m/sec) vs. Young modulus
      (kPa). METHODS: A total of 130 breast lesions in 123 women who underwent SWE
      before ultrasound- guided core needle biopsy or surgical excision were included.
      With the region-of-interest placed over the stiffest areas of the lesion on SWE,
      the quantitative mean, maximum, and standard deviation (SD) of the elasticity
      values were measured in kPa and m/sec for each lesion. The SD was also measured
      with the region-of-interest including the whole breast lesion (wSD). The area
      under the receiver operating characteristic curve (AUC), sensitivity, and
      specificity of each elasticity value measured in kPa and m/sec were compared.
      RESULTS: Of the 130 lesions, 49 (37.7%) were malignant and 81 (62.3%) were
      benign. The AUCs for the mean, maximum, and SD of the elasticity values using kPa
      and m/sec did not differ significantly: mean, 0.974 vs. 0.974; maximum, 0.960 vs.
      0.976; SD, 0.916 vs. 0.916. However, the AUC for wSD showed a significant
      difference: 0.964 (kPa) vs. 0.960 (m/sec) (P=0.036). There was no significant
      difference in the sensitivity and specificity of the mean, maximum, and wSD of
      the elasticity values. However, the specificity of the SD was significantly
      different between the two different measurements: 95.1% (kPa) vs. 87.7% (m/sec)
      (P=0.031). CONCLUSION: The quantitative elasticity values measured in kPa and
      m/sec on SWE showed good diagnostic performance. The specificity of the SD and
      AUC of the wSD measured in kPa were significantly higher than those measured in
      m/sec.

PMID- 24936494
TI  - Sonographic features and ultrasonography-guided fine-needle aspiration of
      metastases to the thyroid gland.
AB  - PURPOSE: To evaluate the characteristic ultrasonographic (US) features of
      metastatic carcinoma to the thyroid, and how accurate US features and
      ultrasonography-guided fine-needle aspiration (US-FNA) are for the diagnosis of
      thyroid metastases. METHODS: Twenty-three thyroid lesions in 23 patients (mean
      age, 66.7 years; range, 46 to 85 years) that had been diagnosed as thyroid
      metastases were included. The composition, echogenicity, margin, shape, presence
      of calcifications, underlying parenchymal echotexture, and vascularity were
      analyzed in US images of the thyroid metastases. Final US assessments were
      categorized into probably benign and suspicious malignancy. The presence of
      suspicious metastatic cervical lymph nodes was noted. The medical records, US-FNA
      cytology, and pathology reports of these patients were retrospectively reviewed.
      RESULTS: Of the 23 thyroid lesions, the general US appearance was mass-forming in
      21 (91.3%) and non-mass-forming in 2 (8.7%). All 23 lesions showed a solid tumor
      composition. Common US features among the 21 mass-forming thyroid metastases were
      hypoechogenicity (81.0%), non-circumscribed margins (90.5%), no calcifications
      (76.2%), and parallel shape (81.0%). Suspicious cervical lymph nodes were present
      in 18 patients (78.3%). Of the 23 lesions, 21 (91.3%) were classified as
      suspicious malignancy, and 2 (8.7%) as probably benign. US-FNA showed diagnostic
      results specific for metastases in 21 of the 22 patients (95.5%) who had
      undergone US-FNA. CONCLUSION: Common US features in thyroid metastasis were
      hypoechogenicity, non-circumscribed margins, no calcifications, parallel shape,
      and the presence of suspicious cervical lymph nodes. US-FNA can be effectively
      used in the diagnosis of thyroid metastasis, preventing unnecessary surgery.

PMID- 24936495
TI  - Application of the Thyroid Imaging Reporting and Data System in thyroid
      ultrasonography interpretation by less experienced physicians.
AB  - PURPOSE: To verify the usefulness of the Thyroid Imaging Reporting and Data
      System (TI-RADS) for thyroid nodule diagnosis by less experienced physicians.
      METHODS: From March 2012 to May 2012, ultrasonography-guided fine needle
      aspiration was performed in 204 thyroid nodules in 195 consecutive patients by
      four less experienced radiologists (<1 year in thyroid imaging). The number of
      suspicious ultrasonography features and the total risk score of each thyroid
      nodule were calculated according to the previous two models suggested by Kwak et
      al. The Delong method was used to compare the areas under the curve (AUCs) of the
      two models. Associations between the two models and the risk of malignancy were
      analyzed using penalized B-splines and the Cochran-Armitage trend test. RESULTS:
      Among 204 thyroid nodules, 65 were malignant and 139 were benign. The probability
      of malignancy tended to increase as the number of suspicious ultrasonography
      features, and the sum of risk scores increased. There was no significant
      difference in the AUCs of the two models (P=0.673). The Cochran-Armitage trend
      test demonstrated an increased risk of malignancy as the number of suspicious
      ultrasonography features and the total risk score increased (P=0.001).
      CONCLUSION: Both the number of suspicious ultrasonography features and the total
      risk score are applicable and show comparable results in the risk stratification
      of thyroid nodules by less experienced radiologists in thyroid imaging.

PMID- 24936496
TI  - Imaging features of complex sclerosing lesions of the breast.
AB  - PURPOSE: The purpose of this study was to evaluate the imaging features of
      complex sclerosing lesions of the breast and to assess the rate of upgrade to
      breast cancer. METHODS: From March 2008 to May 2012, seven lesions were confirmed
      as complex sclerosing lesions by ultrasonography-guided core needle biopsy. Final
      results by either surgical excision or follow-up imaging studies were reviewed to
      assess the rate of upgrade to breast cancer. Two radiologists retrospectively
      analyzed the imaging findings according to the Breast Imaging Reporting and Data
      System classification. RESULTS: Five lesions underwent subsequent surgical
      excision and two of them revealed ductal carcinoma in situ (n=1) and invasive
      ductal carcinoma (n=1). Our study showed a breast cancer upgrade rate of 28.6% (2
      of 7 lesions). Two lesions were stable on imaging follow-up beyond 1 year. The
      mammographic features included masses (n=4, 57.1%), architectural distortion
      (n=2, 28.6%), and focal asymmetry (n=1, 14.3%). Common B-mode ultrasonographic
      features were irregular shape (n=6, 85.7%), spiculated margin (n=5, 71.4 %), and
      hypoechogenicity (n=7, 100%). The final assessment categories were category 4
      (n=6, 85.7%) and category 5 (n=1, 14.3%). CONCLUSION: The complex sclerosing
      lesions were commonly mass-like on mammography and showed the suspicious
      ultrasonographic features of category 4. Due to a high underestimation rate, all
      complex sclerosing lesions by core needle biopsy should be excised.

PMID- 24936497
TI  - Giant cavernous hemangioma coexistent with diffuse hepatic hemangiomatosis
      presenting as portal vein thrombosis and hepatic lobar atrophy.
AB  - A combination of giant hepatic hemangioma and diffuse hemangiomatosis is
      extremely rare in adults. Even when they are large, hemangiomas are soft and
      rarely compress adjacent structures. A 78-year-old man presented with abdominal
      pain and distension. Ultrasonography, computed tomography, and magnetic resonance
      imaging demonstrated a large expansile mass replacing the medial segment and
      caudate lobe with diffusely scattered nodules in the entire liver. The large
      hilar mass contained a central nonenhancing area and had a mass effect, leading
      to left portal vein occlusion. The image findings also revealed two unprecedented
      findings: left lateral segmental atrophy of the liver and recent portomesenteric
      vein thrombosis. The hepatic lesions were confirmed with hemangiomas by
      ultrasonography-guided biopsy. We diagnosed intrahepatic portal vein obstruction
      caused by a mass effect of giant hepatic hemangioma coexistent with diffuse
      hemangiomatosis, resulting in hepatic segmental atrophy and extrahepatic portal
      vein thrombosis. 

PMID- 24936498
TI  - Intrathyroidal thymic tissue mimicking a malignant thyroid nodule in a 4-year-old
      child.
AB  - Intrathyroidal thymic tissue is rare and may be confused with a malignant thyroid
      nodule because of hyperechoic dots mimicking calcifications. We report the case
      of a thyroid nodule with malignant ultrasonographic findings in a 4-year-old
      child, which was confirmed cytologically as ectopic thymic tissue. The
      sonographic findings of ectopic thymus were similar to those of the thymus;
      therefore, clinicians should be familiar with ultrasonography findings of normal
      thymic tissue. 

PMID- 24936499
TI  - Ultrasound elastography for thyroid nodules: recent advances.
AB  - Ultrasonography (US)-based elastography has been introduced as a noninvasive
      technique for evaluating thyroid nodules that encompasses a variety of approaches
      such as supersonic shear imaging and acoustic radiation force impulse imaging as
      well as real-time tissue elastography. However, the diagnostic performances for
      differentiating malignant thyroid nodules from benign ones with elastography as
      an adjunctive tool of gray-scale US is still under debate. In this review
      article, diagnostic performances of conventional US and a combination of
      conventional US and elastography are compared according to the type of
      elastography. Further, the interobserver variability of elastography is presented
      according to the type of elastography. 

PMID- 24936500
TI  - Ultrasound-guided sclerotherapy for benign non-thyroid cystic mass in the neck.
AB  - Surgical excision has traditionally been the treatment of choice for benign non
      thyroid cystic neck masses, including lymphatic malformation, ranula, branchial
      cleft cyst, thyroglossal duct cyst, and parathyroid cyst. However, there is a
      tendency toward recurrence after surgery, and surgery may be accompanied by
      complications, including nerve injuries, vascular injuries, and scar formation.
      Ultrasound-guided sclerotherapy using various agents has been challenged and
      successfully applied as an alternative treatment for benign non-thyroid cystic
      neck masses. This report reviews the available sclerosing agents and describes
      the applications of sclerotherapy to the treatment of benign cystic masses in the
      neck. 

PMID- 24936502
TI  - Usefulness of ultrasound elastography in reducing the number of Breast Imaging
      Reporting and Data System category 3 lesions on ultrasonography.
AB  - PURPOSE: To evaluate the negative predictive value (NPV) of ultrasound (US)
      elastography for non-palpable Breast Imaging Reporting and Data System (BI-RADS)
      category 3 lesions on ultrasonography and to determine whether US elastography is
      helpful in reducing the number of BI-RADS category 3 lesions on ultrasonography.
      METHODS: Two hundred seventy-six consecutive, non-palpable BI-RADS category 3
      lesions in 256 women who underwent US elastography and US-guided core biopsy, and
      who had at least 12 months of follow-up data, comprised our study group. The BI
      RADS final assessment category and elasticity score were prospectively and
      independently classified. The rate of malignancy and NPV according to the
      elasticity score were analysed. We also investigated whether there was a subset
      of BI-RADS category 3 lesions that were of benign histology but negative on
      elastography. RESULTS: Of the 276 non-palpable BI-RADS category 3 lesions, three
      lesions (1.0%) were finally confirmed as ductal carcinomas in situ. No cancers
      were found in the remaining 273 lesions with benign biopsy histology at a mean
      follow-up of 39.4 months (range, 12 to 72 months). The NPV of a negative
      elasticity score (elasticity score of 1) was 99.3% (165 of 166). If BI-RADS
      category 3 lesions showing a negative elasticity score were downgraded to BI-RADS
      category 2, 60.4% (165 of 273) of them with benign histology could have been
      safely followed without biopsy with an increased malignancy rate from 1% (3 of
      276) to 1.8% (2 of 110), which is not significantly higher (P=0.626). CONCLUSION:
      US elastography has the potential to reduce the number of BI-RADS category 3
      lesions on ultrasonography.

PMID- 24936501
TI  - Intra- and interobserver reliability of gray scale/dynamic range evaluation of
      ultrasonography using a standardized phantom.
AB  - PURPOSE: To evaluate intra- and interobserver reliability of the gray
      scale/dynamic range of the phantom image evaluation of ultrasonography using a
      standardized phantom, and to assess the effect of interactive education on the
      reliability. METHODS: Three radiologists (a resident, and two board-certified
      radiologists with 2 and 7 years of experience in evaluating ultrasound phantom
      images) performed the gray scale/dynamic range test for an ultrasound machine
      using a standardized phantom. They scored the number of visible cylindrical
      structures of varying degrees of brightness and made a 'pass or fail' decision.
      First, they scored 49 phantom images twice from a 2010 survey with limited
      knowledge of phantom images. After this, the radiologists underwent two hours of
      interactive education for the phantom images and scored another 91 phantom images
      from a 2011 survey twice. Intra- and interobserver reliability before and after
      the interactive education session were analyzed using K analyses. RESULTS: Before
      education, the K-value for intraobserver reliability for the radiologist with 7
      years of experience, 2 years of experience, and the resident was 0.386, 0.469,
      and 0.465, respectively. After education, the K-values were improved (0.823,
      0.611, and 0.711, respectively). For interobserver reliability, the K-value was
      also better after the education for the 3 participants (0.067, 0.002, and 0.547
      before education; 0.635, 0.667, and 0.616 after education, respectively).
      CONCLUSION: The intra- and interobserver reliability of the gray scale/dynamic
      range was fair to substantial. Interactive education can improve reliability. For
      more reliable results, double- checking of phantom images by multiple reviewers
      is recommended.

PMID- 24936503
TI  - Computer-aided detection system for masses in automated whole breast
      ultrasonography: development and evaluation of the effectiveness.
AB  - PURPOSE: The aim of this study was to evaluate the performance of a proposed
      computer-aided detection (CAD) system in automated breast ultrasonography (ABUS).
      METHODS: Eighty-nine two-dimensional images (20 cysts, 42 benign lesions, and 27
      malignant lesions) were obtained from 47 patients who underwent ABUS (ACUSON
      S2000). After boundary detection and removal, we detected mass candidates by
      using the proposed adjusted Otsu's threshold; the threshold was adaptive to the
      variations of pixel intensities in an image. Then, the detected candidates were
      segmented. Features of the segmented objects were extracted and used for
      training/testing in the classification. In our study, a support vector machine
      classifier was adopted. Eighteen features were used to determine whether the
      candidates were true lesions or not. A five-fold cross validation was repeated 20
      times for the performance evaluation. The sensitivity and the false positive rate
      per image were calculated, and the classification accuracy was evaluated for each
      feature. RESULTS: In the classification step, the sensitivity of the proposed CAD
      system was 82.67% (SD, 0.02%). The false positive rate was 0.26 per image. In the
      detection/segmentation step, the sensitivities for benign and malignant mass
      detection were 90.47% (38/42) and 92.59% (25/27), respectively. In the five-fold
      cross-validation, the standard deviation of pixel intensities for the mass
      candidates was the most frequently selected feature, followed by the vertical
      position of the centroids. In the univariate analysis, each feature had 50% or
      higher accuracy. CONCLUSION: The proposed CAD system can be used for lesion
      detection in ABUS and may be useful in improving the screening efficiency.

PMID- 24936504
TI  - Shear wave velocity measurements using acoustic radiation force impulse in young
      children with normal kidneys versus hydronephrotic kidneys.
AB  - PURPOSE: To measure shear wave velocities (SWVs) by acoustic radiation force
      impulse (ARFI) ultrasound elastography in normal kidneys and in hydronephrotic
      kidneys in young children and to compare SWVs between the hydronephrosis grades.
      METHODS: This study was approved by an institutional review board, and informed
      consent was obtained from the parents of all the children included. Children
      under the age of 24 months were prospectively enrolled. Hydronephrosis grade was
      evaluated on ultrasonography, and three valid ARFI measurements were attempted
      using a high-frequency transducer for both kidneys. Hydronephrosis was graded
      from 0 to 4, and high-grade hydronephrosis was defined as grades 3 and 4.
      RESULTS: Fifty-one children underwent ARFI measurements, and three valid
      measurements for both kidneys were obtained in 96% (49/51) of the patients.
      Nineteen children (38.8%) had no hydronephrosis. Twenty-three children (46.9%)
      had unilateral hydronephrosis, and seven children (14.3%) had bilateral
      hydronephrosis. Seven children had ureteropelvic junction obstruction (UPJO).
      Median SWVs in kidneys with high-grade hydronephrosis (2.02 m/sec) were higher
      than those in normal kidneys (1.75 m/sec; P=0.027). However, the presence of UPJO
      did not influence the median SWVs in hydronephrotic kidneys (P=0.362).
      CONCLUSION: Obtaining ARFI measurements of the kidney is feasible in young
      children with median SWVs of 1.75 m/sec in normal kidneys. Median SWVs increased
      in high-grade hydronephrotic kidneys but were not different between
      hydronephrotic kidneys with and without UPJO.

PMID- 24936505
TI  - Intralesional saline injection for effective ultrasound-guided aspiration of
      benign viscous cystic thyroid nodules.
AB  - PURPOSE: We aimed to evaluate the efficacy and safety of vigorous saline
      injection for viscous cystic thyroid nodules. METHODS: Eighteen patients who
      underwent ultrasound-guided aspiration for viscous cystic thyroid nodules using a
      saline injection were included in our study. After failing to aspirate the cyst
      by the usual method, we vigorously injected saline into the cyst in multiple
      directions to break up and liquefy the viscous cystic contents to enable
      aspiration. The initial and the residual volume of the nodule were calculated,
      and the volume reduction rate and the time taken to perform the aspiration were
      recorded. RESULTS: The mean volume of the cystic nodules before aspiration was
      11.0 mL (range, 1.2 to 26.0 mL), while the postaspiration volume was 4.2 mL
      (range, 0.2 to 14.5 mL). The mean aspirated volume was 63.7% of the initial
      volume. The mean procedure time was 12.4 minutes (range, 5 to 26 minutes). There
      were no significant complications related to the procedure. CONCLUSION: A
      vigorous saline injection followed by aspiration can be a useful method to
      aspirate viscous cystic thyroid nodules as a prestep for further intervention or
      simple management.

PMID- 24936507
TI  - Usefulness of resistive index on spectral Doppler ultrasonography in the
      detection of renal cell carcinoma in patients with end-stage renal disease.
AB  - PURPOSE: The aim of this study was to explore the usefulness of the resistive
      index (RI) on spectral Doppler ultrasonography (US) in the detection of renal
      cell carcinoma (RCC) in patients with end-stage renal disease (ESRD). METHODS:
      Seventeen ESRD patients with kidneys in which renal masses were suspected in
      routine US were subjected. They underwent computed tomography scans and
      additional Doppler US for the characterization of the detected lesions. All
      underwent radical nephrectomy with the suspicion of RCC. Fourteen patients
      finally were included. RI measurements were conducted in the region of the
      suspected renal mass and the background renal parenchyma. The intraclass
      correlation coefficient was used to assess the reproducibility of the RI
      measurement. A paired t-test was used to compare the RI values between the renal
      mass and the background renal parenchyma (P<0.05). RESULTS: The RI values
      measured at the RCCs were significantly lower than those measured at the
      background renal parenchyma (0.41-0.65 vs. 0.75-0.89; P<0.001). The intrareader
      reproducibility proved to be excellent and good for the renal masses and the
      parenchyma, respectively (P<0.001). CONCLUSION: RI on spectral Doppler US is
      useful in detecting RCC in patients with ESRD. The RI values measured at the RCCs
      were significantly lower than those measured at the background renal parenchyma.

PMID- 24936506
TI  - Ductal carcinoma in situ diagnosed using an ultrasound-guided 14-gauge core
      needle biopsy of breast masses: can underestimation be predicted preoperatively?
AB  - PURPOSE: This study was designed to determine the rate of ductal carcinoma in
      situ (DCIS)underestimation diagnosed after an ultrasound-guided 14-gauge core
      needle biopsy (US-14G-CNB) of breast masses and to compare the clinical and
      imaging characteristics between trueDCIS and underestimated DCIS identified
      following surgical excision. METHODS: Among 3,124 US-14G-CNBs performed for
      breast masses, 69 lesions in 60 patients were pathologically-determined to be
      pure DCIS. We classified these patients according to the final pathology after
      surgical excision as those with invasive ductal carcinoma (underestimated group)
      and those with DCIS (non-underestimated group). We retrospectively reviewed and
      compared the clinical and imaging characteristics between the two groups.
      RESULTS: Of the 69 lesions, 21 were shown after surgery to be invasive
      carcinomas; the rateof DCIS underestimation was 30.4%. There were no
      statistically significant differences withrespect to the clinical symptoms, age,
      lesion size, mammographic findings, and ultrasonographic findings except for the
      presence of abnormal axillary lymph nodes as detected on ultrasound. The lesions
      in 2 patients in the non-underestimated group (2/41, 4.9%) and 5 patients in the
      underestimated group (5/19, 26.3%) were associated with abnormal lymph nodes on
      axillary ultrasound, and the presence of abnormal axillary lymph nodes on
      ultrasound was tatistically significant (P=0.016). CONCLUSION: We found a 30.4%
      rate of DCIS underestimation in breast masses based on a US-14G-CNB. The presence
      of abnormal lymph nodes as detected on axillary ultrasound may be useful to
      preoperatively predict underestimation.

PMID- 24936508
TI  - Primary squamous cell carcinoma of thyroid gland with local recurrence:
      ultrasonographic and computed tomographic findings.
AB  - Primary squamous cell carcinoma of the thyroid gland (PSCCT) is a rare malignancy
      that presents with advanced disease and poor prognosis. It is difficult to
      diagnose PSCCT in its early stage because of its rarity and lack of typical
      imaging findings. We experienced an elderly woman with PSCCT confirmed by
      surgery. Although preoperative fine-needle aspiration revealed no malignancy,
      surgical resection was performed because the ultrasonogram showed diffuse
      microcalcifications, which suggested malignancy, and clinically, the mass grew
      rapidly to compress the trachea. Local tumor recurrence was noted at 3 months
      after surgery. Surgical resection or repeat biopsy should be considered if a
      cytologically benign thyroid mass shows imaging or clinical features of
      malignancy. 

PMID- 24936509
TI  - Obstacles and opportunities for the future of genomic medicine.

PMID- 24936510
TI  - Genetics and genomics in Thailand: challenges and opportunities.

PMID- 24936511
TI  - CTSC and Papillon-Lefevre syndrome: detection of recurrent mutations in Hungarian
      patients, a review of published variants and database update.
AB  - Papillon-Lefevre syndrome (PLS; OMIM 245000) is an autosomal recessive condition
      characterized by palmoplantar hyperkeratosis and periodontitis. In 1997, the gene
      locus for PLS was mapped to 11q14-21, and in 1999, variants in the cathepsin C
      gene (CTSC) were identified as causing PLS. To date, a total of 75 different
      disease-causing mutations have been published for the CTSC gene. A summary of
      recurrent mutations identified in Hungarian patients and a review of published
      mutations is presented in this update. Comparison of clinical features in
      affected families with the same mutation strongly confirm that identical
      mutations of the CTSC gene can give rise to multiple different phenotypes, making
      genotype-phenotype correlations difficult. Variable expression of the phenotype
      associated with the same CTSC mutation may reflect the influence of other genetic
      and/or environmental factors. Most mutations are missense (53%), nonsense (23%),
      or frameshift (17%); however, in-frame deletions, one splicing variant, and one
      5' untranslated region (UTR) mutation have also been reported. The majority of
      the mutations are located in exons 5-7, which encodes the heavy chain of the
      cathepsin C protein, suggesting that tetramerization is important for cathepsin C
      enzymatic activity. All the data reviewed here have been submitted to the CTSC
      base, a mutation registry for PLS at http://bioinf.uta.fi/CTSCbase/. 

PMID- 24936513
TI  - Candidate gene analysis using genomic quantitative PCR: identification of
      ADAMTS13 large deletions in two patients with Upshaw-Schulman syndrome.
AB  - Direct sequencing is a popular method to discover mutations in candidate genes
      responsible for hereditary diseases. A certain type of mutation, however, can be
      missed by the method. Here, we report a comprehensive genomic quantitative
      polymerase chain reaction (qPCR) to complement the weakness of direct sequencing.
      Upshaw-Schulman syndrome (USS) is a recessively inherited disease associated with
      severe deficiency of plasma ADAMTS13 activity. We previously analyzed ADAMTS13 in
      47 USS patients using direct sequencing, and 44 of them had either homozygous or
      compound heterozygous mutations. Then, we sought to reveal more extensive defects
      of ADAMTS13 in the remaining three patients. We quantified copy numbers of each
      ADAMTS13 exon in the patients by using genomic qPCR. Each primer pair was
      designed to contain at least one of the two primers used in direct sequencing, to
      avoid missing any exonic deletions. The qPCR demonstrated heterozygous loss of
      exons 7 and 8 in one patient and exon 27 in the other, and further analysis
      revealed c.746_987+373del1782 and c.3751_3892+587del729, respectively. Genomic
      qPCR provides an effective method for identifying extensive defects of the target
      genes. 

PMID- 24936512
TI  - Mutations of NOTCH3 in childhood pulmonary arterial hypertension.
AB  - Mutations of BMPR2 and other TGF-beta superfamily genes have been reported in
      pulmonary arterial hypertension (PAH). However, 60-90% of idiopathic PAH cases
      have no mutations in these genes. Recently, the expression of NOTCH3 was shown to
      be increased in the pulmonary artery smooth muscle cells of PAH patients. We
      sought to investigate NOTCH3 and its target genes in PAH patients and clarify the
      role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in
      41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B,
      or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C
      p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional
      analysis using stable cell lines expressing either wild-type or mutant NOTCH3.
      The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in
      the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated
      into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and
      viability were higher for cells expressing mutant NOTCH3 than for those
      expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients
      and revealed that these mutations were involved in cell proliferation and
      viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The
      results may contribute to the elucidation of PAH pathogenesis. 

PMID- 24936514
TI  - Human leukocyte antigen haplotype phasing by allele-specific enrichment with
      peptide nucleic acid probes.
AB  - Targeted capture of large fragments of genomic DNA that enrich for human
      leukocyte antigen (HLA) system haplotypes has utility in haematopoietic stem cell
      transplantation. Current methods of HLA matching are based on inference or
      familial studies of inheritance; and each approach has its own inherent
      limitations. We have designed and tested a probe-target-extraction method for
      capturing specific HLA haplotypes by hybridization of peptide nucleic acid (PNA)
      probes to alleles of the HLA-DRB1 gene. Short target fragments contained in
      plasmids were initially used to optimize the method followed by testing samples
      of genomic DNA from human subjects with preselected HLA haplotypes and obtained
      approximately 10% enrichment for the specific haplotype. When performed with high
      molecular-weight genomic DNA, 99.0% versus 84.0% alignment match was obtained for
      the specific haplotype probed. The allele-specific target enrichment that we
      obtained can facilitate the elucidation of haplotypes between the 65 kb
      separating the HLA-DRB1 and the HLA-DQA1 genes, potentially spanning a total
      distance of at least 130 kb. Allele-specific target enrichment with PNA probes is
      a straightforward technique that has the capability to improve the resolution of
      DNA and whole genome sequencing technologies by allowing haplotyping of enriched
      DNA and crucially, retaining the DNA methylation profile. 

PMID- 24936515
TI  - Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal
      pterygium syndrome from sub-Saharan Africa.
AB  - Orofacial clefts (OFC) are complex genetic traits that are often classified as
      syndromic or nonsyndromic clefts. Currently, there are over 500 types of
      syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of
      which Van der Woude syndrome (VWS) is one of the most common (accounting for 2%
      of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe
      form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS
      and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan
      Africa. We screened the DNA of eight families with VWS and one family with PPS
      from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected
      exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel
      nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4
      (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously
      reported splice-site variant in exon 7 that changes the acceptor splice site, and
      a known missense variant in exon 7 (p.Leu251Pro). A previously known missense
      variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations
      segregate in the families. Our data confirm the presence of IRF6-related VWS and
      PPS in sub-Saharan Africa and highlights the importance of screening for novel
      mutations in known genes when studying diverse global populations. This is
      important for counseling and prenatal diagnosis for high-risk families. 

PMID- 24936518
TI  - Simple molecular diagnostic method for fragile X syndrome in Egyptian patients:
      pilot study.
AB  - BACKGROUND: Poor knowledge about Fragile X syndrome (FXS) may be a major barrier
      to early diagnosis that could improve quality of life and prognosis especially in
      the developing countries. AIM: The aim of this study was to evaluate simple and
      reproducible method for premutation detection in females of fragile X families
      for the first time in Egypt. SUBJECTS AND METHODS: We have developed a rapid
      modified polymerase chain reaction (PCR)-based screening tool for expanded
      Fragile X mental retardation 1 (FMR1) alleles. This method utilizes betaine as
      additive to facilitate FMR 1 gene amplification. We screened fifty three males,
      thirty two first-degree females; twenty normal healthy controls in addition to
      six reference samples. RESULTS: Simple PCR method showed 16 males with abnormal
      CGG repeats, where 10 of their mothers and four sisters had FMR 1 premutation.
      Consanguineous marriage was present in 66.6% percent of the studied families.
      Studying the correlation between genotype and clinical manifestations showed
      premature ovarian failure in 40% and learning disability in 50% of the studied
      female carriers. CONCLUSION: FXS has to be ruled out in families with
      consanguineous parents, before assuming that familial mental retardation is due
      to autosomal recessive gene defects. Early carrier detection may reduce the
      number of affected children. In conclusion, more studies are still needed of much
      larger sample size with known allele sizes in order to guarantee the accuracy of
      the method used.

PMID- 24936516
TI  - A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia.
AB  - Although coding variants in THAP1 have been causally associated with primary
      dystonia, the contribution of noncoding variants remains uncertain. Herein, we
      examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among
      1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant
      in contrast to 1/1574 controls (P < 0.01). Dystonia classification included
      cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw
      opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified
      (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In
      comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A
      variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform
      2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that
      c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A
      variant showed extensive apoptosis with relatively fewer cells in the G2 phase of
      the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed
      that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and
      proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate
      that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia. 

PMID- 24936519
TI  - The relation of PON1-L55M gene polymorphism and clinical manifestation of
      Behcet's disease.
AB  - PURPOSE: Behcet's disease is a multisystem disease characterized by recurrent
      oral and genital ulcers, relapsing uveitis, mucocutaneous, articular,
      gastrointestinal, neurologic, and vascular manifestations. Paraoxonase is
      believed to play an important role in protection of LDL and HDL particles from
      oxidation, in antioxidant effect against lipid peroxidation on cellular
      membranes, and in anti-inflammatory process. Lipid peroxidation and free oxygen
      radicals have been thought to play a role in pathogenesis of BD. The association
      of paraoxonase gene polymorphisms with Behcet's Disease in a group of Turkish
      patients with clinical manifestations and healthy controls has been investigated.
      PATIENTS AND METHODS: Paraoxonase (PON-1-L55M) gene polymorphism was investigated
      in 50 Behcet patients and 50 healthy individuals with a PCR/RFLP method. RESULTS:
      There were significant differences between patients and the control group in
      allele frequencies of the PON1 L55M polymorphism (p=0.04). Also, when patients
      were compared with the control group according to clinical manifestations, this
      statistical significance was getting sharper. Compared with the PON55 L allele,
      the M allele was associated with greater than 3.5 fold (OR 3.5, 95% CI 1.3-8.9)
      increased risk of ocular (OR 2.4, 95% CI 1.1-5.3), 2.4 fold joint and 3.1 fold
      (OR 3.1, 95% CI 1.1-8.4) central nervous system manifestations of BD. CONCLUSION:
      The PON L55M gene polymorphism seemed to play a role in the pathogenesis of BD.

PMID- 24936520
TI  - The pH optimum of native uracil-DNA glycosylase of Archaeoglobus fulgidus
      compared to recombinant enzyme indicates adaption to cytosolic pH.
AB  - Uracil-DNA glycosylase of Archaeoglobus fulgidus (Afung) in cell extracts
      exhibited maximal activity around pH 6.2 as compared to pH 4.8 for the purified
      recombinant enzyme expressed in Escherichia coli. Native Afung thus seems to be
      adapted to the intracellular pH of A. fulgidus, determined to be 7.0+/-0.1. Both
      recombinant and native Afung exhibited a broad temperature optimum for activity
      around 80 degrees C, reflecting the A. fulgidus optimal growth temperature of 83
      degrees C. Adaption to the neutral conditions in the A. fulgidus cytoplasm might
      be due to covalent modifications or accessory factors, or due to a different
      folding when expressed in the native host. 

PMID- 24936521
TI  - Smooth muscle contamination analysis in clinical oncology gene expression
      research.
AB  - Gene expression profiling is one of the most explored methods for studying
      cancers and microarray data repositories have become a rich and important
      resource. The most common human cancers develop in organs that are walled by
      smooth muscles. The only method of sample extraction free of unintentional
      contamination with surrounding tissue is microdissection. Nevertheless, such an
      approach is implemented infrequently. In the light of the above, there is a
      possibility of smooth muscle contamination in a large portion of publicly
      available data. In this study, 2292 publicly available microarrays were analysed
      to develop a simple screening method for detecting smooth muscle contamination.
      Microarray Inspector software was used to perform the tests since it has the
      unique ability to use many selected genes and probesets in a single group as a
      tissue definition. Furthermore, the test was dataset-independent. Two strategies
      of tissue definition were explored and compared. The first one depended on Tissue
      Specific Genes Database (TiSGeD) and BioGPS web resources, which themselves were
      based on meta-analysis of thousands of microarrays. The second method was based
      on a differential gene expression analysis of a few hundred preselected arrays.
      The comparison of the two methods proved the latter to be superior. Among the
      tested samples of undefined contamination, nearly half were identified to
      possibly contain significant smooth muscle traces. The obtained results equip
      researches with a simple method of examining microarray data for smooth muscle
      contamination. The presented work serves as an example of how to create
      definitions when searching for other possible contaminations. 

PMID- 24936523
TI  - Editorial: looking back.

PMID- 24936522
TI  - Investigation of asparagine deamidation in a SOD1-based biosynthetic human
      insulin precursor by MALDI-TOF mass spectrometry.
AB  - A biosynthetic human insulin precursor displayed enhanced susceptibility to
      deamidation at one particular site. The present study was undertaken to monitor
      progress of precursor deamidation at successive manufacturing stages. MALDI
      TOF/TOF MS in combination with controlled endoproteinase Glu-C and endoproteinase
      Asp-N proteolysis was used for rapid and unambiguous determination of deamidated
      residue within the investigated structure. Close inspection of isotopic
      distribution patterns of peptides resulting from enzymatic digestion enabled
      determination of distinct precursor forms occurring during the production
      process. Asn, Asp, isoAsp and succinimide derivatives of the amino acid at
      position 26 were unambiguously identified. These modifications are related to the
      leader peptide of a precursor encompassing amino acid sequence corresponding to
      that of superoxide dismutase [Cu-Zn] (SOD1 1, EC=1.15.1.1). Monitoring of
      precursor deamidation process at successive manufacturing stages revealed that
      the protein folding stage was sufficient for a prominent replacement of
      asparagine by aspartic and isoaspartic acid and the deamidated human insulin
      precursor constituted the main manufactured product. Conversion proceeded through
      a succinimide intermediate. Significant deamidation is associated with the
      presence of SNG motif and confirms results achieved previously on model peptides.
      Our findings highlight an essential role of the specific amino acid sequence on
      accelerated rate of protein deamidation. To our knowledge, this is the first time
      that such a dramatic change in the relative abundance of Asp and isoAsp resulting
      from protein deamidation process is reported. 

PMID- 24936525
TI  - Adhesively luted zirconia restorations: why and how?

PMID- 24936526
TI  - On the importance of image formation optics in the design of infrared
      spectroscopic imaging systems.
AB  - Infrared spectroscopic imaging provides micron-scale spatial resolution with
      molecular contrast. While recent work demonstrates that sample morphology affects
      the recorded spectrum, considerably less attention has been focused on the
      effects of the optics, including the condenser and objective. This analysis is
      extremely important, since it will be possible to understand effects on recorded
      data and provides insight for reducing optical effects through rigorous
      microscope design. Here, we present a theoretical description and experimental
      results that demonstrate the effects of commonly-employed cassegranian optics on
      recorded spectra. We first combine an explicit model of image formation and a
      method for quantifying and visualizing the deviations in recorded spectra as a
      function of microscope optics. We then verify these simulations with measurements
      obtained from spatially heterogeneous samples. The deviation of the computed
      spectrum from the ideal case is quantified via a map which we call a deviation
      map. The deviation map is obtained as a function of optical elements by
      systematic simulations. Examination of deviation maps demonstrates that the
      optimal optical configuration for minimal deviation is contrary to prevailing
      practice in which throughput is maximized for an instrument without a sample.
      This report should be helpful for understanding recorded spectra as a function of
      the optics, the analytical limits of recorded data determined by the optical
      design, and potential routes for optimization of imaging systems. 

PMID- 24936527
TI  - First evaluation of the threat posed by antifouling biocides in the Southern
      Adriatic Sea.
AB  - The CARISMA project (characterization and ecological risk analysis of antifouling
      biocides in the Southern Adriatic Sea) aims to appraise the quality of the
      Southern Adriatic Sea between Italy (Apulia region) and Albania and, in
      particular, the impact due to the use of biocidal antifouling coatings. Under
      this project, a preliminary survey at the main hot spots of contamination (e.g.
      ports and marinas) was conducted at the end of the nautical season in 2012.
      Chemical seawater analyses were complemented with ecotoxicological assays and the
      results were analyzed by principal component analysis (PCA). As expected, PCA
      splits the Albanian and Italian ports, according to the different degrees of
      contamination indicated for the two countries by the experimental data,
      highlighting the most critical situation in one port of Apulia. In addition, in
      order to assess the potential adverse ecological effects posed by antifouling
      agents (i.e. tributyltin (TBT)-irgarol-diuron) on non-target marine organisms,
      hazard quotients (HQ) were calculated. The results showed a low risk posed by
      irgarol and diuron whereas the probability of adverse effects was high in the
      case of TBT.

PMID- 24936528
TI  - A synthetic biochemistry molecular purge valve module that maintains redox
      balance.
AB  - The greatest potential environmental benefit of metabolic engineering would be
      the production of high-volume commodity chemicals, such as biofuels. Yet, the
      high yields required for the economic viability of low-value chemicals is
      particularly hard to achieve in microbes owing to the myriad competing
      biochemical pathways. An alternative approach, which we call synthetic
      biochemistry, is to eliminate the organism by constructing biochemical pathways
      in vitro. Viable synthetic biochemistry, however, will require simple methods to
      replace the cellular circuitry that maintains cofactor balance. Here we design a
      simple purge valve module for maintaining NADP(+)/NADPH balance. We test the
      purge valve in the production of polyhydroxybutyryl bioplastic and isoprene-
      pathways where cofactor generation and utilization are unbalanced. We find that
      the regulatory system is highly robust to variations in cofactor levels and
      readily transportable. The molecular purge valve provides a step towards
      developing continuously operating, sustainable synthetic biochemistry systems.

PMID- 24936529
TI  - Evidence for interacting two-level systems from the 1/f noise of a
      superconducting resonator.
AB  - The performance of a great variety of electronic devices--ranging from
      semiconductor transistors to superconducting qubits--is hampered by low-frequency
      noise with spectra proportional to 1/f. The ubiquity and negative impact of 1/f
      noise has motivated intensive research into its cause, and it is now believed to
      originate from a bath of fluctuating two-level defect states (TLSs) embedded in
      the material. This phenomenon is commonly described by the long-established
      standard tunnelling model (STM) of independent TLS. A key prediction of STM is
      that the noise should vanish at low temperatures. Here we report measurements on
      superconducting microresonators over previously unattainable, very long time
      scales that show an increase in 1/f noise at low temperatures and low microwave
      power, contrary to the STM. We propose a new generalised tunnelling model that
      includes significant interaction between multiple TLSs, which fully describes
      these observations, as well as recent studies of individual TLS lifetimes in
      superconducting qubits.

PMID- 24936530
TI  - Sulodexide: it is time for a program against chronic venous disease.

PMID- 24936531
TI  - Pharmacological profile of sulodexide.
AB  - Since its introduction, sulodexide has been used on and off for several
      indications. More recently this agent has become revitalized and tested in newer
      indications. Sulodexide is composed of glycosaminoglycan that includes a mixture
      of fast-moving heparin and dermatan sulfate. It exerts its anticoagulant and
      antithrombotic action through interactions with both AT and HCII. Sulodexide has
      been proven to have effects on the fibrinolytic system, platelets, endothelial
      cells, inflammation and more recently metalloproteases. The administration of
      sulodexide results in the release of lipoprotein lipase and has been shown to
      reduce the circulating level of lipids. It has also shown to decrease the
      viscosity of both whole blood and plasma. Sulodexide differs from heparin in its
      oral bioavailability and longer half-life. There is also less bleeding associated
      with sulodexide. In addition, oral administration of sulodexide does not
      interfere with the pharmacologic actions of commonly used agents. Similar to
      heparin, sulodexide releases TFPI which contributes to its antithrombotic effect
      and anti-inflammatory properties. Sulodexide has been proven to be effective in
      peripheral arterial thrombosis and venous thrombosis. It is also clinically
      active in the treatment of venous leg ulcers and intermittent claudication. More
      recent data suggest that sulodexide can be used in tinnitus and in vascular
      vertigo. Additional studies in these indications are required. Sulodexide was
      generally safe and well tolerated in the clinical trials, without any severe
      bleeding complications. Therefore sulodexide appears to be a good treatment for
      all arterial and venous diseases and for the prevention of progression of
      disease. 

PMID- 24936532
TI  - Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous
      disease.
AB  - Inflammation represents an important epiphenomenon in the etiopathogenesis of
      chronic venous disease, a worldwide debilitating condition affecting millions of
      subjects. The pathophysiology of chronic venous disease (CVD) is based on the
      hemodynamic abnormalities in conjunction to alterations in cellular and
      extracellular matrix biocompounds. The endothelial dysfunction results from early
      perturbation in the endothelium linked to glycocalyx injury and promoted by
      inflammatory cells and mediators (such as matrix metalloproteinases and
      interleukins), which lead to progressive dilation of the vein resulting in
      chronic venous insufficiency. Activated leukocytes during the inflammatory
      process release enzymes, free radicals, chemokines and inflammatory cytokines in
      the vessel microenvironment, which are responsible for the changes of the venous
      wall and venous valve, reflux and venous hypertension, and the
      development/progression of tissue destruction and skin changes. Sulodexide, a
      highly purified mixture of glycosaminoglycans composed by 80% fast moving heparin
      and 20% of dermatan sulphate, exhibits anti-thrombotic and profibrinolytic
      properties, restoring also the essential endothelial glycocalyx.
      Glycosaminoglycan sulodexide has been also characterized to reduce the release of
      inflammatory cytokines/chemokines and to inhibit the matrix metalloproteinases
      related proteolytic cascades, counteracting endothelial dysfunctions. The
      pleiotropic effects of sulodexide set the basis for a very promising agent in
      treating the spectrum of CVD. 

PMID- 24936533
TI  - Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological
      roles and pharmacological effects.
AB  - The glycocalyx is a jelly layer covering the endothelium constituted by
      glycosaminoglycans (GAGs), proteoglycans and adsorbed plasma proteins. This
      structure take part in several physiological and pathological vascular events.
      The glycocalyx acts as mechanosensor to shear stress and participates to
      regulation of vascular tone, permeability, coagulation and complement activation.
      Moreover it regulates the interaction and activation of blood cells with
      endothelial cells. The presence of a thick, normal glycocalyx is required for
      physiological vascular functions, whereas these functions are impaired by its
      damage by noxious agents. Indeed, glycocalyx alterations are involved in the
      pathogenesis of atherosclerosis, ischemia-reperfusion and diabetic vascular
      complications. GAGs such as sulodexide are promising agents to control
      endothelial dysfunction. They act at multiple levels: they promote glycocalyx
      reconstitution, control glycocalyx degrading enzymes, exert anti-inflammatory
      effects and have anti-apoptotic and anti-senescence effects on endothelial cells.
      Clinical studies support the evidence that glycosaminoglycans are useful to
      restore a normal endothelial function. 

PMID- 24936534
TI  - Role of sulodexide in the treatment of CVD.
AB  - Treatment of vascular diseases should be based on established pathophysiological
      concepts, and this also applies to chronic venous disease (CVD). On the basis of
      the latest research in this field, this paper summarizes the most advanced
      pathophysiological knowledge regarding the hemodynamics of the large veins and of
      the microcirculation, the endothelial function and inflammation, and the use of
      sulodexide in the treatment of CVD. The emerging theories on the pathophysiology
      of CVD consider inflammation, endothelial glycocalyx dysfunction, and the
      consequent changes in the extracellular matrix to play key roles in the
      development of CVD, and support a renewed interest in the research and
      application of sulodexide. As part of active approach to the treatment of CVD
      including edema and trophic venous alterations, sulodexide could help to
      alleviate progressive signs and symptoms of disease in any clinical CEAP class of
      CVD, from C1 to C6. 

PMID- 24936535
TI  - Severity of chronic venous disease and anatomic distribution of valvular
      incompetence.
AB  - AIM: The aim of the study was to examine the association between anatomical
      patterns of valvular incompetence and the severity of venous insufficiency in
      patients with chronic venous disease. METHODS: A total of 211 consecutive
      patients (70% females) were referred from the vascular clinic to undergo a
      Doppler ultrasound examination. The extent and anatomical pattern of valvular
      incompetence was noted using CEAP criteria. Clinical classes C1-6 for each
      patient were expressed as a string of binary digits and translated into a
      clinical ordinal score. In this way, higher grade signs were not obscuring lower
      grade signs and non-parametric analysis could include a wider range of clinical
      data. RESULTS: Varicose veins were the main complaint in 33% of the patients. 54%
      had at least one incompetent deep vein, 80% had incompetent perforators. Clinical
      severity increased with age, but was not related with gender. The presence of
      deep venous incompetence did not account for significant increase in signs.
      Superficial incompetence, especially if involving two or more segments, was most
      commonly seen in patients with severe signs. A linear regression model for
      clinical ordinal score identified non-saphenous superficial reflux and small
      saphenous vein reflux as the strongest predictors of clinical severity.
      CONCLUSION: CEAP clinical classes can be translated into a clinical ordinal
      score, which is useful for data analysis. In a group with chronic venous
      disorders, clinical status is associated mostly with the condition of superficial
      and calf perforating veins.

PMID- 24936536
TI  - Effects of high hemodynamics upon the morphology of the walls of the great
      saphenous vein and splenic vein.
AB  - AIM: Studies have shown that the incidence and development of pathological
      changes in the walls of the great saphenous vein and splenic vein are closely
      related to high venous pressure. Such changes are referred to as "vascular
      adaptive remodeling responses under high venous pressure". The proposition of the
      concept of vascular remodeling contributes to our knowledge of pathological
      changes in the venous wall (dilation of the venous lumen and thickening of the
      venous wall). In the present study, we compared the histomorphology and
      cytomorphology of the walls of varicose great saphenous veins (GSVs) and diseased
      splenic veins (SVs) to investigate the remodeling of the venous wall under high
      hemodynamic pressure. METHODS: We collected 34 samples of varicose great
      saphenous veins and diseased splenic veins. Thirty-four samples of normal great
      saphenous veins and splenic veins were also collected (control group). Samples
      were made into slices and observed under light microscopy and electron
      microscopy. The thickness of the tunica intima and tunica media as well as the
      inner diameter of the venous lumen were measured. RESULTS: Under light
      microscopy, the walls of varicose veins stained with H&E were unevenly thickened,
      and those of diseased splenic veins were evenly thickened; mucoid degeneration of
      the tunica intima of varicose veins was not obvious by Masson staining (2/20
      cases). The boundary between the tunica intima and tunica media was clearly
      defined. Uneven hyperplasia of muscular connective tissues was observed. For the
      diseased splenic-vein group, mucoid degeneration of the tunica intima was obvious
      (8/14 cases), with an unclearly defined boundary between the tunica intima and
      tunica extima. Uneven hyperplasia of muscular connective tissues was also
      observed. Differences in the thickness and inner diameter of the tunica intima
      and tunica media between the great saphenous vein and the splenic vein were
      significantly different. Under electron microscopy, mitochondrial degeneration in
      endothelial cells was observed in both groups. Increased numbers of rough
      endoplasmic reticula in the cytoplasm of smooth muscle cells, ribosomes and
      mitochondria and decreased numbers of myofilaments were also observed.
      CONCLUSION: High hemodynamics affected the remodeling of varicose great saphenous
      veins and diseased splenic veins. The histomorphology of visceral veins showed
      more significant pathological changes than that of peripheral veins. Similar
      cytomorphological changes were observed in both groups.

PMID- 24936537
TI  - The IUA program of accreditation of vascular centers has just taken off:
      multidisciplinary cares are the best way to manage the vascular patients.

PMID- 24936538
TI  - Long-term progression of contralateralcarotid artery disease after
      endarterectomy: is there a need for Duplex surveillance?

PMID- 24936539
TI  - Evaluation of the content of the Anatolian Journal of Cardiology by the Editor in
      Chief.

PMID- 24936540
TI  - The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat
      aorta.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of pravastatin
      and nebivolol in the atherosclerotic process including inflammation and oxidative
      stress in rat aorta. METHODS: This experimental randomized controlled study
      comprised of 35 Wistar albino rats. Nomega-nitro-L-arginine methyl ester (L-NAME)
      - induced vascular inflammation and arteriosclerosis were treated with both of
      the pharmacologic agents. All were divided into 5 equal groups: the control,
      group I: L-NAME -15 days, group II: L-NAME 30+ nebivolol, group III: L-NAME -30+
      pravastatin, group IV: L-NAME - 30 days. Serum ceruloplasmin, uric acid, total
      antioxidant capacity (TAC), total cholesterol (T.Chol), low density lipoprotein
      (LDL), high density lipoprotein (HDL), triglyceride (TG) were analyzed. Medial
      thickening and leukocyte infiltration status were examined histopathologically.
      The results were compared with control group and with each other using Kruskal
      Wallis and Mann-Whitney U test. RESULTS: Pravastatin diminished the rise of
      ceruloplasmin, which was taken as an index of inflammation (p=0.002). Pravastatin
      and nebivolol decreased the L-NAME induced oxidative stress (p=0.001, 0.002,
      respectively). Nebivolol diminished the rise of LDL (p=0.04). Pravastatin lowered
      T.Chol, LDL and TG levels (p=0.001, 0.008, 0.040, respectively). HDL values were
      not changed significantly. CONCLUSION: In conclusion, 15 days of statin therapy
      attenuated vascular inflammation and lowered the rised lipid levels (LDL,
      T.cholesterol and TG). Both the nebivolol and pravastatin exhibited antioxidant
      property. These documented beneficial effects of both of the drugs may improve
      the clinical outcomes of patients with hypertension or hyperlipidemia by
      additional studies.

PMID- 24936541
TI  - The role of endothelial nitric oxide synthase gene G894T and intron 4 VNTR
      polymorphisms in hemodialysis patients with vascular access thrombosis.
AB  - OBJECTIVE: Endothelial nitric oxide synthase (eNOS) gene is a candidate gene in
      cardiovascular and renal diseases. Several polymorphic variations have been
      identified in eNOS gene. We investigated a potential role of arteriovenous
      fistula (AVF) thrombosis and intron 4 and G894T polymorphisms in chronic renal
      failure. METHODS: We performed a case-control observational study involving 79
      with/without AVF thrombosis in chronic renal failure patients. All subjects were
      genotyped by the polymerase chain reaction (PCR) and PCR-Restriction Fragment
      Length Polymorphism. Genotype distribution and allele frequencies were compared
      between groups using the chi-square test. RESULTS: Genotype frequencies in
      patients with thrombosis were not significantly different from those of patients
      without thrombosis for eNOS G894T polymorphism (p=0.1). eNOS gene intron 4 a
      allele distributions seems to be associated with thrombosis in the groups.
      CONCLUSION: This study revealed that there was an association between eNOS intron
      4 polymorphism and thrombosis in chronic renal failure patients. This data will
      be helpful in planning further eNOS association studies in vascular access
      thrombosis.

PMID- 24936542
TI  - Prognostic significance of sICAM-1 and sVCAM-1 molecules for cardiac surgery in
      pediatric patients with pulmonary hypertension.
AB  - OBJECTIVE: To investigate preoperative and postoperative blood levels of soluble
      intercellular and vascular cell adhesion molecules (sICAM-1, sVCAM-1) in patients
      with and without pulmonary hypertension (PAH) due to congenital heart disease and
      left to right (L-R) shunt and to determine whether these molecules can be used as
      reliable prognostic markers of endothelial activity to predict surgical outcomes.
      METHODS: In this observational prospective cohort study; 42 patients, operated
      for L-R shunt were divided into three groups. Group 1: L-R shunt without PAH,
      Group 2: L-R shunt with PAH, Group 3: L-R shunt with PAH and postoperative low
      cardiac output syndrome (LCOS). Their sICAM-1 and sVCAM-1 levels were measured
      preoperatively (sICAM-0, sVCAM-0) and on the first (sICAM-1, sVCAM-1) and fifth
      postoperative days (sICAM-2, sVCAM-2).ROC curve for various cut-off levels of
      sICAM-0, sVCAM-0 in differentiating PAH patients with and without LCOS. RESULTS:
      In Group 3, sICAM-0 and sVCAM-2 levels were higher than Group 1 and 2. The ROC
      curve demonstrated a significant association between sICAM-0 in patients with L-R
      shunt and PAH (Group 2 and 3) and the development of LCOS (area under the curve:
      0.98, p<0.01 and 0.97, p<0.01, respectively). At a sICAM-0 concentration >359
      ng/mL, there was a sensitivity of 90% and specificity of 95% for identification
      of LCOS in patients with L-R shunt and PAH (AUC: 0.98, 95% CI: 0.95-1.02,
      p<0.01). CONCLUSION: High preoperative sICAM-1 molecule may be used to predict
      postoperative dichotomous outcome in patients with PAH associated with L-R shunt.

PMID- 24936543
TI  - Progress of ISSS in Turkey from 2007 to 2010: on the eve of the 2014 event.

PMID- 24936544
TI  - Re: 'Better data ? Bigger data'.

PMID- 24936545
TI  - Identifying risk factors for severe hypoglycemia in hospitalized patients with
      diabetes.
AB  - OBJECTIVE: Some of the deleterious effects of hypoglycemia in hospitalized
      patients include increased rates of mortality and longer length of stay. Our
      primary objective was to identify the risk factors associated with severe
      hypoglycemia to identify those patients at highest risk. METHODS: The medical
      records of 5,026 patients with diabetes mellitus (DM) admitted in 2010 were
      reviewed to identify those patients that developed severe hypoglycemia (blood
      glucose [BG] <40 mg/dL). We performed chi2 tests to assess statistical
      significance. Adjusted logical regression was used to determine the risk factors
      for hypoglycemia in the hospital. RESULTS: Out of 5,026 DM patients included in
      our review, 81 experienced severe hypoglycemia (1.6%). Statistically higher
      proportions of chronic kidney disease (CKD; 69.1% vs. 46.9%, P<.001), congestive
      heart failure (CHF; 48.1% vs. 28.5%, P<.001), sepsis (49.4% vs. 12.5%, P<.001),
      insulin use (45.7% vs. 26.04%, P = .000), type 1 DM (21% vs. 5.1%, P = .000), and
      cirrhosis (14.8% vs. 7.2%, P = .009) were seen in the severe hypoglycemic group
      compared to the nonsevere hypoglycemic group. Overall, 84% of patients who
      experienced an episode of severe hypoglycemia in the hospital (BG <40 mg/dL) had
      a previous episode of hypoglycemia (BG <70 mg/dL). The odds ratios (ORs) for type
      1 DM, sepsis, previous hypoglycemia, and insulin use were 3.43 (95% confidence
      interval [CI] 1.81, 6.49), 2.64 (95% CI 1.6, 4.35), 46.1 (95% CI 24.76, 85.74),
      and 1.66 (95% CI 1.02, 2.69), respectively. CONCLUSION: Prior episodes of
      hypoglycemia in the hospital, the presence of type 1 DM, insulin use, and sepsis
      were identified as independent risk factors for the development of severe
      hypoglycemia in the hospital.

PMID- 24936546
TI  - Successful fertility restoration after allogeneic hematopoietic stem cell
      transplantation.
AB  - OBJECTIVE: Myeloablative conditioning regimens given prior to hematopoietic stem
      cell transplantation (HSCT) frequently cause permanent sterility in men. In
      patients with sickle cell disease (SCD) we use a nonmyeloablative regimen with
      sirolimus, alemtuzumab, and low-dose total-body irradiation (300 centigrays) with
      gonadal shielding preceding allogeneic HSCT. We report here the restoration of
      azoospermia in a patient with SCD after allogeneic HSCT. We discuss the impact of
      our patient's underlying chronic medical conditions and the therapies he had
      received (frequent blood transfusions, iron chelating drugs, ribavirin,
      hydroxyurea, opioids), as well as the impact of the nonmyeloablative conditioning
      regimen on male gonadal function, and we review the literature on this topic.
      METHODS: We determined the patient's reproductive hormonal values and his semen
      parameters before, during, and after HSCT and infertility treatment. In addition,
      we routinely measured his serum laboratory parameters pertinent to SCD and
      infertility, such as iron and ferritin levels. A karyotype analysis was performed
      to assess the potential presence of Klinefelter syndrome. Finally, imaging
      studies of the patient's brain and testes were done to rule out further
      underlying pathology. RESULTS: A 42-year-old man with SCD, transfusional iron
      overload, and hepatitis C underwent a nonmyeloablative allogeneic HSCT. One year
      later he desired to father a child but was found to be azoospermic in the context
      of hypogonadotropic hypogonadism. Restoration of fertility was attempted with
      human chorionic gonadotropin (2,000 IU) plus human menopausal gonadotropin (75 IU
      follicle-stimulating hormone) injected subcutaneously 3 times weekly. Within 6
      months of treatment, the patient's serum calculated free testosterone value
      normalized, and his sperm count and sperm motility improved. After 10 months, he
      successfully initiated a pregnancy through intercourse. The pregnancy was
      uncomplicated, and a healthy daughter was delivered naturally at term.
      CONCLUSION: Despite exposure to several gonadotoxins, transfusional iron overload
      and nonmyeloablative conditioning with radiation causing severe testicular
      atrophy suggesting extensive damage to seminiferous tubules and possibly Leydig
      cells, gonadotropins were efficacious in restoring our patient's reproductive
      capability.

PMID- 24936547
TI  - Low Testosterone Levels are Frequent in Patients with Acute Respiratory Failure
      and are Associated with Poor Outcomes.
AB  - OBJECTIVE: Low testosterone level is a common finding in critically ill patients
      with trauma, shock, and sepsis. However, its prevalence and outcomes in patients
      with primary acute respiratory failure is unknown; low testosterone could
      contribute to respiratory muscle weakness and further compromise ventilation in
      these patients. METHODS: We aimed to determine the prevalence, severity, and
      effects of hypotestosteronemia in patients with acute respiratory failure in a 16
      bed single academic center medical intensive care unit (ICU). We studied 30 men
      who required mechanical ventilation for >=24 hours for a primary diagnosis of
      acute respiratory failure. Blood samples were drawn on ICU day 1 and day 3 to
      measure serum levels of total and free testosterone. RESULTS: Hypotestosteronemia
      (level below the lower reference limit) was present on day 1 in 93.1% (total
      testosterone) and 76.7% (free testosterone) of patients and on day 3 in 94.4%
      (total testosterone) and 100% (free testosterone) of patients. Sex hormone
      binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone,
      luteinizing hormone, and thyroid function levels were all within stated reference
      ranges. Total and free testosterone levels correlated inversely with ventilator
      days and ICU length of stay. CONCLUSION: Hypotestosteronemia is common in
      mechanically ventilated patients with primary acute respiratory failure and may
      contribute to longer ICU stay. Further studies are needed to determine the effect
      of testosterone replacement on short- and long-term outcomes in these patients.

PMID- 24936548
TI  - The Prevalence of Gestational Diabetes Mellitus Among Asian Females is Lower
      Using the New 2013 World Health Organization Diagnostic Criteria.
AB  - OBJECTIVE: To determine the impact of the new 2013 World Health Organization
      (WHO) criteria for gestational diabetes mellitus (GDM) diagnosis on GDM
      prevalence and pregnancy outcomes in Asian ethnic groups compared to the 1999 WHO
      criteria. METHODS: A retrospective cohort study included 855 pregnant females of
      Chinese, Malay, and Asian Indian ethnicity at high risk of GDM who underwent 75-g
      oral glucose tolerance tests (OGTTs) between July 2008 and June 2010 in a
      tertiary center in Singapore. GDM prevalence, reclassification, and pregnancy
      outcomes were determined using the 2013 and 1999 diagnostic cutoffs for fasting
      and 2-hour postglucose (PG) values. RESULTS: The prevalence of GDM was reduced
      from 28.8% to 21.1% when the 2013 criteria were used. Overall, 10.2% subjects
      were reclassified from GDM to normal using the 2013 criteria, and 2.6% were
      reclassified from normal to GDM, giving a net reclassification rate of 12.8%.
      Reclassification from GDM to normal was greatest among Chinese, followed by Asian
      Indians, but the prevalence rate was unchanged among Malays. Babies of mothers
      who were reclassified from normal to GDM were more likely to have birth weight
      >95th centile and shoulder dystocia. CONCLUSION: The prevalence of GDM was
      reduced when the 2013 criteria were used, with the greatest reduction seen among
      Chinese, followed by Asian Indians. Lowering the fasting cutoff as per the new
      criteria identified a select group of patients who might benefit from GDM
      treatment. However, raising the 2-hour PG cutoff would miss a significant number
      of patients who might potentially benefit from GDM treatment.

PMID- 24936549
TI  - Thyroid Carcinoma Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography
      Among Individuals Without Prior Evidence of Thyroid Disease: Relevance and
      Clinicopathologic Features.
AB  - OBJECTIVE: The expanding use of 18F-fluorodeoxyglucose positron emission
      tomography (18F-FDG-PET) has contributed to an increasing number of thyroid
      incidentalomas. The present study aimed to estimate the prevalence of 18F-FDG-PET
      thyroid incidentalomas and evaluate the clinicopathologic features of thyroid
      malignancies detected by 18F-FDG-PET. METHODS: We reviewed all 18F-FDG-PET exams
      performed at the Portuguese Institute of Oncology, Lisbon, between 2007 and 2012
      (n = 9,374). The inclusion criteria were focal thyroid uptake and absence of
      known thyroid disease. RESULTS: Focal thyroid uptake was observed in 60 out of
      9,374 18F-FDG-PET exams (prevalence of 0.64%). Fine-needle aspiration cytology
      (FNAC) was performed in 23 patients and reported as malignant in 14 cases (56.5%
      primary thyroid carcinoma; 4.3% secondary malignancy), as benign in 7 cases
      (30.5%) and as follicular lesion of undetermined significance in 2 cases (8.7%).
      Fourteen patients had surgery. A final histologic diagnosis of papillary thyroid
      carcinoma was established in 12 cases (52.2%). Three were multifocal (25.0%); 8
      had extrathyroidal extension (66.7%); 5 had angioinvasion (41.7%); 3 had lymph
      nodes metastases (25.0%) and 2 showed lung metastases (16.7%). Overall, 91.7%
      were classified as intermediate or high risk. All patients had radioiodine
      therapy. At the last observation (mean follow-up was 29.9 months), persistent or
      recurrent disease was identified in 4 patients (33.3%) and none died from thyroid
      malignancy. CONCLUSIONS: Thyroid carcinomas disclosed by 18F-FDG-PET are
      associated with aggressive histological criteria likely to carry a worse
      prognosis.

PMID- 24936550
TI  - A Novel Deletion Mutation in the MEN1 Gene in a Patient with Prolactinoma and a
      Family History of Pancreatic Tumors.
AB  - OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
      tumor syndrome caused by mutations in the MEN1 gene. Mutations in this tumor
      suppressor gene are often associated with neuroendocrine tumors. Here we describe
      a novel deletion mutation at codon 304 in the MEN1 gene of a patient with a
      prolactinoma and strong family history of pancreatic tumors. METHODS: We describe
      the patient's clinical course and mutational analysis and review the relevant
      literature. RESULTS: A 30-year-old pregnant female was referred to our
      institution's psychological department for treatment of depression. She had
      developed a prolactinoma at age 17 and was being treated with 1 mg/week of
      cabergoline. A medical interview revealed a family history of pancreatic islet
      cell and other tumors; her mother died of pancreatic cancer, her brother is
      living with gastrinoma, and her sister died of leiomyosarcoma. Extensive
      examinations performed after delivery, including laboratory tests and computed
      tomography (CT) scans, did not reveal any other tumors. Mutational analysis of
      the MEN1 gene identified a heterozygous deletion mutation (c911_914delAGGT) at
      codon 304. This mutation produces a frameshift at p.304Lys and might disturb the
      splicing of intron 6 due to the lack of a donor site. The predicted menin protein
      from the mutated allele is truncated at amino acid 328. CONCLUSION: We report a
      novel deletion mutation (c911_914delAGGT) in the MEN1 gene that was likely
      associated with the patient's prolactinoma and her strong family history of
      pancreatic tumors.

PMID- 24936552
TI  - A case of nonischemic cardiomyopathy associated with autoimmune polyglandular
      syndrome type III.
AB  - OBJECTIVE: To report a case of nonischemic dilated cardiomyopathy associated with
      autoimmune polyglandular syndrome (APS) type III. METHODS: A review of our
      patient's medical records was undertaken, and her clinical history,
      investigations, and outcome are described. In addition, a literature review of
      nonischemic dilated cardiomyopathy occurring in association with autoimmune
      polyendocrinopathies was performed. RESULTS: APS is diagnosed once a patient has
      developed at least 2 organ specific autoimmune diseases. APS III involves a
      combination of autoimmune diabetes and Graves' disease without adrenal
      insufficiency. Autoimmune cardiomyopathies are not described as a feature of this
      condition; however, there are a few reported cases of patients with autoimmune
      polyendocrinopathies developing a nonischemic dilated cardiomyopathy. In this
      case, a 30-year-old female developed vitiligo, Graves' disease, and latent
      autoimmune diabetes of the adult (LADA) over a 5-year period before presenting
      with conscious ventricular tachycardia (VT). This evolved into acute severe
      biventricular failure within a few weeks, which failed to resolve after adequate
      treatment of her other autoimmune conditions. CONCLUSION: Although nonischemic
      cardiomyopathies have been associated with APS in a few published cases, this is
      the first case to our knowledge in a patient with APS III.

PMID- 24936553
TI  - Significant hypercortisolism during fractionated radiotherapy in a patient with a
      large corticotroph adenoma: a case report and literature review.
AB  - OBJECTIVE: We describe a patient with a large, invasive corticotroph adenoma who
      developed severe hypercortisolism shortly after starting fractionated
      radiotherapy. METHODS: We reviewed the patient's clinical course, along with
      relevant literature for similar reported cases. RESULTS: A 29-year-old man was
      referred for radiotherapy for a residual and recurrent, invasive corticotroph
      adenoma. Prior to radiotherapy, he had a normal urine free cortisol (UFC) level
      of 44.7 MUg/24 hours, with minimal symptoms. Within 2 weeks of radiotherapy, he
      developed hypertension, ankle edema, and hypokalemia (potassium level, 2.8
      mEq/L), with a markedly elevated UFC level of 9,203 MUg/24 hours. His UFC
      gradually decreased and normalized by the end of radiotherapy. One month later,
      the patient became adrenal insufficient, with a nondetectable 24-hour UFC. His
      adrenal function slowly recovered in 3 months. We are aware of only one previous
      case report of clinically significant hypercortisolism following radiotherapy in
      Cushing disease. CONCLUSION: Radiotherapy may result in acute severe
      hypercortisolism in patients with a large corticotroph adenoma. This uncommon,
      but clinically significant, acute adverse effect of radiotherapy suggests that
      clinical observation and biochemical monitoring during or soon after radiotherapy
      may be indicated.

PMID- 24936551
TI  - How Short is Too Short According to Parents of Primary Care Patients.
AB  - OBJECTIVE: Height is a physical trait on a continuum. The threshold between
      normal and abnormal is arbitrarily set but can potentially influence medical
      decision-making. We sought to examine parents' perceptions of adult heights and
      associated demographic factors. METHODS: Parents of pediatric primary care
      patients of various heights completed a one-time survey. Parents answered the
      question "How short is too short?" for adult males and females. The results were
      summarized as median [interquartile range]. Factors significantly associated with
      height threshold by simple linear regression were included in a multivariable
      mixed effects analysis of covariance model. RESULTS: A total of 1,820 surveys
      were completed (83% response rate; 1,587 females, 231 males). The median
      threshold height deemed too short for adult females was 56 inches [48, 59] among
      male respondents and 57 inches [50, 60] among females (P<.05). The median
      threshold height for adult males was 61 inches among males [60, 64] and females
      [59, 66] (P<.05). The median of male minus female heights per respondent (delta
      heights) was 5 [2, 7] inches. Factors found to be significant main effects in a
      parsimonious model were sex of the adult considered, height of respondent, sex of
      respondent, respondent race, primary care practice, income, and having concerns
      about their child's height. CONCLUSION: Taller acceptable height thresholds were
      perceived by respondents who were taller, wealthier, white, female, from nonurban
      practices, or who had a personal concern about their child's height. Male heights
      were expected to be taller than female heights. Such traits may influence who is
      concerned and more likely to seek medical treatment for their children.

PMID- 24936554
TI  - Visual vignette.

PMID- 24936555
TI  - A 24-week, prospective, randomized, open-label, treat-to-target pilot study of
      obese type 2 diabetes patients with severe insulin resistance to assess the
      addition of exenatide on the efficacy of u-500 regular insulin plus metformin.
AB  - OBJECTIVE: To compare the efficacy of 500 U/mL (U-500) regular insulin +
      metformin with U-500 regular insulin + metformin + exenatide in improving
      glycemic control in patients with severely insulin-resistant type 2 diabetes
      mellitus (T2DM). METHODS: Thirty patients with T2DM and severe insulin resistance
      were screened, and 28 were randomized to regular insulin U-500 + metformin or the
      GLP-1 analog exenatide, U-500, and metformin. Glycated hemoglobin (HbA1c) levels,
      body weight, and insulin doses were documented at baseline and at 3 and 6 months.
      The number and severity hypoglycemic episodes were noted. RESULTS: There were 7
      males and 7 females in each group (U-500 + metformin and U-500 + metformin +
      exenatide). Overall, U-500 insulin + metformin, either alone or with the addition
      of exenatide, resulted in a significant improvement in HbA1c in both groups, with
      no significant difference between the 2 groups. There was no meaningful weight
      change in those utilizing exenatide. Those on U-500 insulin and metformin alone
      had a tendency toward some weight gain. No severe hypoglycemia occurred during
      the study period. Symptomatic hypoglycemia was more common in the group on
      exenatide, but this occurred in only 5 patients, and the clinical significance of
      this is uncertain. Insulin dosage changes on U-500 regular insulin were variable
      but tended to be lower in those subjects on exenatide. CONCLUSIONS: U-500 regular
      insulin + metformin is effective for the treatment of T2DM patients with severe
      insulin resistance. The addition of exenatide may ameliorate potential weight
      gain but provides no additional improvement in glycemia.

PMID- 24936556
TI  - Changes in body weight after treatment of primary hypothyroidism with
      levothyroxine.
AB  - OBJECTIVE: Surprisingly few studies have examined weight change in hypothyroid
      patients after initiation of levothyroxine (LT4) therapy. Our study aimed to
      investigate weight change after initiation of LT4 treatment for primary
      hypothyroidism. METHODS: Using electronic medical records from Boston Medical
      Center, Boston, Massachusetts, we performed a retrospective cohort study between
      January 1, 2003, and February 1, 2011. Adults >=18 years of age with newly
      diagnosed primary hypothyroidism with an initial thyroid-stimulating hormone
      (TSH) level >=10 mIU/L were identified. Patients with postsurgical
      hypothyroidism, thyroid cancer, and a history of radioactive iodine or head/neck
      irradiation, congestive heart failure, anorexia nervosa, end-stage renal disease,
      cirrhosis, pregnancy, or use of prescription weight-loss medications were
      excluded. TSH and weight at diagnosis and up to 24 months after LT4 initiation
      were collected. Weight change was assessed at the first posttreatment serum TSH
      level <5 mIU/L. RESULTS: A total of 101 patients (mean age, 48 +/- 15 years; 71%
      women) were included. Initial median TSH was 18.3 mIU/L (range, 10.1 to 710.5
      mIU/L) and initial median weight was 79.6 kg (range 41.5 to 167.5 kg).
      Posttreatment median TSH level was 2.3 mIU/L (range, 0.04 to 5 mIU/L), and weight
      change at a median of 5 months (range, 1.1 to 25.6 months) was -0.1 kg (range, 
      20.6 to 7.7 kg). Initial median body mass index (BMI) of 95 of the patients was
      29.3 kg/m2 (range, 19.5 to 56.1 kg/m2), and the median change in BMI was -0.1
      kg/m2 (range, -7.1 to 3.3 kg/m2). Only 52% of patients lost weight, with a mean
      weight loss of 3.8 +/- 4.4 kg. Gender, race, education, insurance type, age,
      initial TSH level, time to normalization of TSH, and initial weight were not
      associated with changes in weight or BMI. CONCLUSION: Contrary to popular belief,
      our study of 101 patients with primary hypothyroidism showed that no significant
      weight change occurs after initiation of LT4 treatment.

PMID- 24936557
TI  - Silent renal stones in primary hyperparathyroidism: prevalence and clinical
      features.
AB  - OBJECTIVE: (1) To evaluate the prevalence of silent nephrolithiasis in patients
      with primary hyperparathyroidism (PHPT) compared with controls, and (2) To
      characterize clinically PHPT patients with silent renal stones. METHODS: We
      reviewed clinical data for 141 patients with PHPT and without symptoms or history
      of nephrolithiasis in whom renal ultrasonography was performed at diagnosis. A
      total of 141 sex- and age- matched subjects with abdomen ultrasonography obtained
      for reasons different from urinary symptoms served as controls. RESULTS: Silent
      nephrolithiasis was more prevalent in PHPT patients than in controls (11.35% vs.
      2.13%; P = .003). Among patients with PHPT, those with silent renal stones showed
      higher serum calcium and parathyroid hormone levels and met surgical criteria,
      regardless of nephrolithiasis, more frequently than those without renal stones.
      CONCLUSION: The prevalence of silent nephrolithiasis is increased in patients
      with PHPT as compared with controls. Moreover, it seems likely that silent renal
      stone disease could identify a subset of PHPT patients with more severe disease.
      Accordingly, we suggest ultrasonographic screening of nephrolithiasis in all PHPT
      patients. Further studies are needed to better characterize this clinical entity.

PMID- 24936558
TI  - Medication failure.

PMID- 24936559
TI  - Malignant pheochromocytoma secreting vasoactive intestinal peptide and response
      to sunitinib: a case report and literature review.
AB  - OBJECTIVE: Malignant pheochromocytoma is rare and may be sporadic or have a
      genetic basis. Vasoactive intestinal peptide (VIP)-secreting pheochromocytoma has
      rarely been described in the literature, and treatment remains challenging in the
      absence of well-controlled randomized trials. The hypoxia-inducible factor
      vascular endothelial growth factor axis has been implicated in pheochromocytoma
      when associated with germline Von-Hippel-Lindau (VHL) or succinate dehydrogenase
      (SDH) mutations, suggesting potential clinical activity of sunitinib in this
      setting. METHODS: We present a case report of a patient with a VIP-secreting
      malignant pheochromocytoma manifested as severe watery diarrhea, with an
      exquisite clinical response to sunitinib. We review this rare clinical entity and
      the potential role of sunitinib in this context. RESULTS: A 51-year-old male
      initially presented with a pheochromocytoma causing symptoms related to
      norepinephrine excess. He underwent adrenalectomy, which resulted in complete
      resolution of his symptoms. Three years later, he developed multifocal metastatic
      disease from his primary tumor, showing immunohistochemical evidence of VIP
      production accompanied by severe watery diarrhea and hypokalemia. The patient had
      a rapid, complete, and durable clinical response to sunitinib, but with only a
      minor radiological response and without significant toxicity. Genetic testing was
      negative for germline mutations in VHL, SDHB, SDHC, SDHD, transmembrane protein
      127 (TMEM127) and for neurofibromatosis type 1 (NF-1). CONCLUSION: To the best of
      our knowledge, this is the first report of a case of malignant VIP-producing
      pheochromocytoma that was responsive to sunitinib.

PMID- 24936560
TI  - Apparent Mineralocorticoid Excess Caused by a Novel Mutation in 11-beta
      Hydroxysteroid Dehydrogenase Type 2 Enzyme: Its Genetics and Response to Therapy.
AB  - OBJECTIVE: To present a case of apparent mineralocorticoid excess (AME) due to a
      novel mutation in the HSD11B2 gene and describe the patient's response to
      therapy. METHODS: The clinical, biochemical, and genetic features of the proband
      and his family are presented. For the genetic study, DNA was extracted from
      peripheral leucocytes. The exons and exon-intron boundaries were polymerase chain
      reaction (PCR)-amplified and directly sequenced. RESULTS: A 10-year-old male
      presented with hypertension (HTN) and weakness and was found to have hypokalemia
      of 2.6 mmol/L. Plasma renin was undetectable, and plasma and urinary aldosterone
      were low. Serum cortisol and deoxycorticosterone were normal. Daily urinary
      excretion of cortisol was normal, but urinary and serum cortisone levels were
      undetectable. The patient was treated with spiranolactone with inadequate
      response. A small dose of dexamethasone was added and led to excellent control of
      HTN and hypokalemia. Genetic studies showed a novel missense biallelic mutation
      changing guanine to adenine in exon 3 (c.G526A) of the HSD11B2. This mutation
      changes the amino acid aspartic acid to asparagine at codon 176 (p.D176N). A
      monoallelic form of the same mutation was found in the parents and 3 of his 4
      healthy siblings but not in a healthy sister or 100 normal subjects. CONCLUSIONS:
      A case of AME due to a novel mutation in HSD11B2 showed the usual features of AME
      but exhibited an inadequate response to spironolactone. A small dose of
      dexamethasone resulted in an excellent response.

PMID- 24936561
TI  - Periarticular hand joint limitation syndromes in diabetes.

PMID- 24936563
TI  - The right tool for the job.

PMID- 24936562
TI  - Serum monocyte chemokine protein-1 levels before and after parathyroidectomy in
      patients with primary hyperparathyroidism.
AB  - OBJECTIVE: To investigate the effects of parathyroidectomy on serum monocyte
      chemokine protein-1 (MCP-1) levels in patients with primary hyperparathyroidism
      (PHPT). METHODS: Forty-three PHPT patients, age 56 +/- 12 years, underwent
      minimally invasive parathyroidectomy. Serum samples were collected at 0 and 15 to
      20 minutes after parathyroid adenoma removal. Serum samples were stored at -70
      degrees C until time of assay. RESULTS: In 40 PHPT patients with a single
      adenoma, MCP-1 levels decreased from 342 +/- 103 to 250 +/- 77 pg/mL (P<.001) 15
      to 20 minutes after parathyroid adenoma removal. MCP-1 levels were positively
      correlated with intact parathyroid hormone (PTH) levels (R = 0.47; P<.01). In 3
      PHPT patients with double parathyroid adenoma, MCP-1 levels did not decrease
      after removal of the first adenoma but decreased 15 to 20 minutes after second
      adenoma removal. CONCLUSION: Our results provide evidence that the decrease in
      serum intact PTH due to minimally invasive parathyroidectomy results in an
      immediate decrease in serum MCP-1 levels.

PMID- 24936564
TI  - Analysis of internet-based patient education materials related to pituitary
      tumors.
AB  - OBJECTIVE: The Internet has become a primary and ubiquitous information source
      for patient education material (PEM); however, the information provided may not
      be appropriate for the average patient to comprehend. Various national healthcare
      organizations have recommended that PEM be written at or below the sixth-grade
      level. The purpose of this study was to assess the readability of pituitary tumor
      related PEMs available on the Internet. METHODS: Fifty-one PEMs on pituitary
      tumors were downloaded from professional society and clinical practice websites.
      Analysis of readability was performed using 4 different readability indices:
      Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Simple
      Measure of Gobbledygook (SMOG), and Gunning Frequency Measure of Gobbledygook
      (Gunning FOG). RESULTS: Scores from the FKGL, SMOG, and Gunning FOG scales
      correspond to reading grade levels. Therefore, a higher number corresponds to
      higher difficulty and lower readability. The average grade level of the PEMs
      according to the readability indices were as follows: FKGL = 11.71 (11th to 12th
      grades), SMOG = 14.56 (college level), and Gunning FOG = 14.86 (college level).
      For the FRES, higher scores imply easier readability. The average FRES was 40.19
      (fairly difficult-between 10th and 11th grades). CONCLUSION: These findings
      suggest that online pituitary tumor-related material may be too difficult for
      comprehension by the majority of the targeted patient population. Keeping the
      reading level of PEMs at or below the sixth grade may improve understanding of
      this disease and its management for pituitary tumor patients.

PMID- 24936565
TI  - Body weight changes in a large cohort of patients subjected to thyroidectomy for
      a wide spectrum of thyroid diseases.
AB  - OBJECTIVE: Patients undergoing thyroidectomy often complain of weight gain. The
      aim of this study was to longitudinally evaluate body-weight changes in patients
      thyroidectomized for euthyroid and hyperthyroid conditions in order to identify
      predictive factors. METHODS: Anthropometric data and thyroid function parameters
      were retrospectively reviewed for 267 thyroidectomized patients before and 40 to
      60 days and 9 months after surgery. Presurgery diagnoses included benign (Graves
      disease, nodular toxic goiter, nodular nontoxic goiter) and malignant
      (differentiated thyroid cancer) conditions. RESULTS: Mean preintervention weight
      of the entire study group significantly increased (P<.0001) 9-months after
      thyroidectomy, from 70.8 +/- 16.0 to 72.5 +/- 16.4 kg. Body weight increased in
      156 (58.4%) patients, decreased in 59 (22.1%) patients, and remained stable in 52
      (19.5%) patients. A multiple regression model was constructed by entering the
      percentage of body-weight change 9 months postsurgery as the dependent variable
      and age, sex, presurgery body mass index, percentage of weight change 40 to 60
      days postsurgery, presurgery thyroid-stimulating hormone (TSH) level, TSH level
      40 to 60 days postsurgery, TSH level 9 months postsurgery, thyroid disease
      driving thyroidectomy, and type of surgical intervention as the covariates. No
      significant relationship was found for any of the covariates tested, with the
      exception of percentage of body-weight change at 40 to 60 days postsurgery
      (correlation coefficient, 0.869; [95% confidence interval, 0.692 to 1.046;
      P<.0001]). CONCLUSION: Thyroidectomy is associated with a significant increase in
      body weight, which is not limited to patients with Graves disease. Postsurgery
      TSH levels do not account for subsequent body-weight changes. Short-term changes
      (40 to 60 days postsurgery) in body weight are highly predictive of the outcome
      at 9 months, suggesting that early factors related to thyroidectomy per se might
      play a role.

PMID- 24936566
TI  - Hyperparathyroid crisis due to asymmetric parathyroid hyperplasia with a massive
      ectopic parathyroid gland.
AB  - OBJECTIVE: To report a rare case of primary hyperparathyroidism presenting with
      hyperparathyroid crisis due to parathyroid hyperplasia with ectopic glands.
      METHODS: We present the initial clinical manifestations, laboratory results,
      radiologic and surgical findings, and management in a patient who had
      hyperparathyroid crisis. The pertinent literature and management options are also
      reviewed. RESULTS: A 60-year-old female presented with hyperparathyroid crisis
      requiring preoperative stabilization with rehydration, diuresis, bisphosphonate
      therapy, and ultimately hemodialysis. Parathyroidectomy revealed asymmetric 4
      gland hyperplasia, with a massive ectopic parathyroid gland in the
      tracheoesophageal groove extending into the mediastinum. Her postoperative course
      was complicated by hungry bone syndrome and hypocalcemia. CONCLUSION: This case
      illustrates the rare occurrence of hyperparathyroid crises due to asymmetric
      parathyroid hyperplasia with a massive ectopic parathyroid gland.

PMID- 24936567
TI  - Utility of Adrenocorticotropic Hormone in Assessing the Response to
      Transsphenoidal Surgery for Cushing's Disease.
AB  - OBJECTIVES: To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics
      in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS)
      and to determine the value of early postoperative ACTH levels in predicting
      subsequent hypocortisolemia. METHODS: Following TSS for CD, serum cortisol and
      plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid
      coverage. RESULTS: A total of 26 subjects (25 female) underwent 28 operations.
      Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat
      TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who
      achieved hypocortisolemia had significantly lower ACTH levels by 19 hours
      postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in
      82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined
      to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to
      hypocortisolemia. Follow-up data were available on 25 patients for a median of 23
      months. Three subjects who achieved initial surgical remission had disease
      recurrence at 19, 24, and 36 months; all of these subjects had a postoperative
      nadir serum cortisol levels <3 MUg/dL and plasma ACTH <20 pg/mL. CONCLUSION:
      Following TSS for CD, plasma ACTH declined prior to achievement of
      hypocortisolemia in most subjects. In the majority, the ACTH level reached a
      nadir of <20 pg/mL. Low early postoperative ACTH levels predict early
      hypocortisolemia but may not accurately predict long-term remission.

PMID- 24936568
TI  - Atypical femoral fracture in an osteogenesis imperfecta patient successfully
      treated with teriparatide.
AB  - OBJECTIVE: We report a case of a successfully healed atypical femoral fracture
      (AFF) following treatment with teriparatide in a patient with osteogenesis
      imperfecta (OI). To our knowledge, no successful treatment of AFFs with
      teriparatide in this subpopulation has ever been described. METHODS: This is a
      case report of an AFF treated with teriparatide. RESULTS: The patient was treated
      with hormone replacement therapy for 18 years and bisphosphonates for 9 years
      before suffering a spontaneous AFF in the form of a dislocated noncomminute
      transverse fracture of the right femoral shaft, and an open reduction and
      internal fixation (ORIF) with a T2 Femoral Nail was done. Due to nonunion and
      another fracture distal to the nail, the patient was reoperated on with exchange
      ORIF and off-label treatment with teriparatide 20 MUg/day was started. An X-ray 1
      month later showed early signs of fracture healing. A subsequent X-ray 6 months
      after the last operation showed a solid healing of both right femoral fractures.
      CONCLUSION: This is a rare case that highly suggests a potential fracture healing
      effect of teriparatide treatment and highlights a potential significant practical
      therapeutic consideration in relation to the management of AFF with delayed
      healing.

PMID- 24936569
TI  - Online social networks that connect users to physical activity partners: a review
      and descriptive analysis.
AB  - BACKGROUND: The US Centers for Disease Control and Prevention have identified a
      lack of encouragement, support, or companionship from family and friends as a
      major barrier to physical activity. To overcome this barrier, online social
      networks are now actively leveraging principles of companion social support in
      novel ways. OBJECTIVE: The aim was to evaluate the functionality, features, and
      usability of existing online social networks which seek to increase physical
      activity and fitness among users by connecting them to physical activity
      partners, not just online, but also face-to-face. METHODS: In September 2012, we
      used 3 major databases to identify the website addresses for relevant online
      social networks. We conducted a Google search using 8 unique keyword
      combinations: the common keyword "find" coupled with 1 of 4 prefix terms
      "health," "fitness," "workout," or "physical" coupled with 1 of 2 stem terms
      "activity partners" or "activity buddies." We also searched 2 prominent
      technology start-up news sites, TechCrunch and Y Combinator, using 2 unique
      keyword combinations: the common keyword "find" coupled with 1 of 2 stem terms
      "activity partners" and "activity buddies." Sites were defined as online social
      health activity networks if they had the ability to (1) actively find physical
      activity partners or activities for the user, (2) offer dynamic, real-time
      tracking or sharing of social activities, and (3) provide virtual profiles to
      users. We excluded from our analysis sites that were not Web-based, publicly
      available, in English, or free. RESULTS: Of the 360 initial search results, we
      identified 13 websites that met our complete criteria of an online social health
      activity network. Features such as physical activity creation (13/13, 100%) and
      private messaging (12/13, 92%) appeared almost universally among these websites.
      However, integration with Web 2.0 technologies such as Facebook and Twitter
      (9/13, 69%) and the option of direct event joining (8/13, 62%) were not as
      universally present. Largely absent were more sophisticated features that would
      enable greater usability, such as interactive engagement prompts (3/13, 23%) and
      system-created best fit activities (3/13, 23%). CONCLUSIONS: Several major online
      social networks that connect users to physical activity partners currently exist
      and use standardized features to achieve their goals. Future research is needed
      to better understand how users utilize these features and how helpful they truly
      are.

PMID- 24936570
TI  - The impact of rollator loading on gait and fall risk in neurorehabilitation - a
      pilot study.
AB  - Abstract Purpose: Rollator loading is an application used clinically sometimes to
      improve functional integrity and security of the patients' gait. As empirical
      evidence supporting this intervention is equivocal, the purpose of this study was
      to examine the effects of rollator loading on several gait parameters and fall
      risk. Methods: An explicatory experiment with a follow-up cohort study of falls
      was conducted. In the experimental part of the study, participants (n = 25) were
      evaluated three times by means of different gait and fall risk assessments,
      whereby each trial was carried out with different rollator loading (0, 4.5 and 9
      kg, respectively). Participants were blinded towards the applied load. In
      addition, the odds ratio of falls with respect to rollator loading in all-day
      rehabilitation life was determined. Results: No changes in spatio-temporal gait
      parameters and fall risk in relation to a particular load could be identified by
      clinical measures in the tested sample. A separate sub-group analysis
      (Parkinson's disease, hemiparesis and ataxia) showed only little impact of the
      load in each case. Rollator loading had no impact on the odds ratio of inpatient
      fall risk. Conclusion: On the basis of our findings, weighting of rollators can
      neither be discouraged nor recommended. Implications for Rehabilitation Unless
      more research is has been conducted on this topic, rollator loading can neither
      be recommended nor discouraged in individuals suffering from neurologic diseases.
      There is more research needed to examine the impact on ambulation in distinct
      conditions such as severe ataxia and fear of falling.

PMID- 24936571
TI  - Providing assistive technology in Italy: the perceived delivery process quality
      as affecting abandonment.
AB  - PURPOSE: The study brings together three aspects rarely observed at once in
      assistive technology (AT) surveys: (i) the assessment of user
      interaction/satisfaction with AT and service delivery, (ii) the motivational
      analysis of AT abandonment, and (iii) the management/design evaluation of AT
      delivery services. METHODS: 15 health professionals and 4 AT experts were
      involved in modelling and assessing four AT Local Health Delivery Service
      (Centres) in Italy through a SWOT analysis and a Cognitive Walkthrough. In
      addition 558 users of the same Centres were interviewed in a telephone survey to
      rate their satisfaction and AT use. RESULTS: The overall AT abandonment was equal
      to 19.09%. Different Centres' management strategies resulted in different
      percentages of AT disuse, with a range from 12.61% to 24.26%. A significant
      difference between the declared abandonment and the Centres' management
      strategies (p = 0.012) was identified. A strong effect on abandonment was also
      found due to professionals' procedures (p = 0.005) and follow-up systems (p =
      0.002). CONCLUSIONS: The user experience of an AT is affected not only by the
      quality of the interaction with the AT, but also by the perceived quality of the
      Centres in support and follow-up. Implications for Rehabilitation AT abandonment
      surveys provide useful information for modelling AT assessment and delivery
      process. SWOT and Cognitive Walkthrough analyses have shown suitable methods for
      exploring limits and advantages in AT service delivery systems. The study
      confirms the relevance of person centredness for a successful AT assessment and
      delivery process.

PMID- 24936572
TI  - [Surgical options for reducing body weight].
AB  - Obesity is a leading preventable cause of death worldwide, with increasing
      prevalence in adults and children, and authorities view it as one of the most
      serious public health problems of the 21st century. Sixty-two percent of the
      Hungarian adult population has overweight and 27% is morbidly obese and,
      therefore, it is a significant interest to treat this condition. The authors
      review the diagnosis and the associated diseases of morbid obesity. The initial
      enthusiasm with the gastric band has settled now, as the long-term outcome showed
      only very limited reduction in the excess body weight and the complication rate
      was as high as 50%. The sleeve gastrectomy may induce 60-70% of excess weight
      loss, however, the long term follow-up data is very limited. The Roux-en-Y
      gastric bypass is the gold-standard of the bariatric procedures, with proven 60
      75% excess weight loss and 80% type 2 diabetes remission. The body image usually
      changes with weight loss, and frequently a body contouring procedure is required
      to improve it. Multi-disciplinary team of super-specialised doctors is required
      to perform these procedures.

PMID- 24936573
TI  - [Prevalence and possible causes of hypospadias].
AB  - Hypospadias is the most common congenital malformation of the male external
      genitalia. After the heart and circulatory system, it is the second most common
      developmental disorder in males. It is due to a midline fusion defect of the male
      urethra, which results in a misplaced urethral meatus. Hypospadias may be distal,
      medial and proximal. It may occur as an isolated defect or it may develop
      together with other genital disorders (retention of testes in one or both sides,
      microphallus, bifid scrotum) or with malformation of other organs. In some cases
      syndromic forms may also occur. Genetic factors play a crucial role in the
      occurrence of early developmental defect, but endocrine and environmental factors
      may also be important in the aetiology of hypospadias. It may be associated with
      various sex and autosomal chromosomal abnormalities. Monogenic and chromosomal
      causes of hypospadias accounts for about in 30% of all cases, while genetic
      factors remain unknown in 70% of cases. The authors summarize the development of
      the male external genitalia, the prevalence and possible causes of hypospadias.
      They propose that better understanding of the pathogenesis of the disease may
      contribute to the prevention and decreased prevalence of the disease.

PMID- 24936574
TI  - [Experience with implanted ports for venous access between 2005 and 2012].
AB  - INTRODUCTION: During chemotherapy of cancer patients, vein inflammation may
      develop which may lead to pain and difficulty in blood sampling. The use of
      implanted venous access ports may overcome these problems. With a correct use of
      needles, venous port membrane may be pierced 2000-2500 times. AIM: The aim of the
      authors was to analyze their experience with venous access ports and evaluate
      whether insertion of venous ports occurred in an optimal time. METHOD: A
      retrospective study of 63 patients who received venous access ports between 2005
      and 2012 was carried out. Complication rate and the time of venous port insertion
      were analysed. RESULTS: Of the 63 patients, the venous access port was removed in
      22 patients because it was no longer required (n = 14) due to the development of
      complications (n = 8). 24 patients died from the underlying disease and 17
      patients are still alive with the venous port in place. CONCLUSIONS: In the
      period studied patients with venous access ports had an improved quality of life.
      However, the authors conclude that venous access ports were not inserted in an
      optimal time.

PMID- 24936575
TI  - [The health of female physicians in Hungary. A longitudinal perspective].
AB  - INTRODUCTION: There is a worldwide rising tendency of women who decide to become
      physician. One of the most remarkable fields of investigation is the well-being
      of female doctors. AIM: To study the prevalence of somatic and reproductive
      morbidity in a representative sample of Hungarian female physicians and compare
      it with a control group of graduated women. METHOD: Data for this epidemiological
      study were collected from 2515 female physicians in 2013. Graduated women from a
      representative survey (Hungarostudy 2013) served as controls. The results were
      compared to the previous (2003-2004) representative female physicians' survey.
      RESULTS: We found that the prevalence of chronic somatic morbidity among female
      physicians was significantly higher than that in the respective control groups. A
      larger proportion of female medical doctors were characterized by time-to
      pregnancy interval longer than one year, and undergoing infertility therapy and
      miscarriages, compared to the control female population, while the same
      prevalence of terminations of pregnancy was found. CONCLUSIONS: The longitudinal
      perspective confirmed the existence of the "Hungarian female physicians'
      paradox".

PMID- 24936578
TI  - Permeation tests of glove and clothing materials against sensitizing chemicals
      using diphenylmethane diisocyanate as an example.
AB  - Diphenylmethane diisocyanate (MDI) is a sensitizing chemical that can cause
      allergic contact dermatitis and asthma. Protective gloves and clothing are
      necessary to prevent skin exposure. Breakthrough times are used for the selection
      of chemical protective gloves and clothing. In the EN 374-3:2003 European
      standard, breakthrough time is defined as the time in which the permeation
      reaches the rate of 1.0 ug min(-1) cm(-2) through the material. Such breakthrough
      times do not necessarily represent safe limits for sensitizing chemicals. We
      studied the permeation of 4,4'-MDI through eight glove materials and one clothing
      material. The test method was derived from the EN 374-3 and ASTM F 739 standards.
      All measured permeation rates were below 0.1 ug min(-1) cm(-2), and thus, the
      breakthrough times for all the tested materials were over 480min, when the
      definitions of EN 374-3 and ASTM F 739 for the breakthrough time were used. Based
      on the sensitizing capacity of MDI, we concluded that a cumulative permeation of
      1.0 ug cm(-2) should be used as the end point of the breakthrough time
      determination for materials used for protection against direct contact with MDI.
      Using this criterion for the breakthrough time, seven tested materials were
      permeated in <480min (range: 23-406min). Affordable chemical protective glove
      materials that had a breakthrough time of over 75min were natural rubber, thick
      polyvinylchloride, neoprene-natural rubber, and thin and thick nitrile rubber. We
      suggest that the current definitions of breakthrough times in the standard
      requirements for protective materials should be critically evaluated as regards
      MDI and other sensitizing chemicals, or chemicals highly toxic via the skin. 

PMID- 24936576
TI  - [Autoimmune pancreatitis in a patient with ulcerative colitis simulating a
      pancreatic tumor].
AB  - Pancreatic endocrine and/or exocrine functional disorders can be commonly
      detected in patients with inflammatory bowel diseases. Autoimmune pancreatitis is
      a rare disease and its co-existence with inflammatory bowel disease has been
      rarely reported. The diagnosis of autoimmune pancreatitis is difficult due to
      variable nonspecific symptoms, and the high rate of asymptomatic cases. The
      conventional imaging scans (ultrasonography, computed tomography, retrograde
      cholangiography) are usually not sensitive enough and they are frequently not
      able to differentiate between inflammatory and malignant tumorous diseases of the
      pancreas. The authors present the case history of a patient who developed both
      ulcerative colitis and autoimmune pancreatitis. The morphological changes of the
      pancreas detected by ultrasonography suggested the presence of pancreatic cancer,
      and this diagnosis was supported by the elevated level of serum CA19-9. Computed
      tomography failed to identify abnormalities in the pancreas and, finally,
      endoscopic ultrasound combined with fine needle aspiration cytology confirmed the
      diagnosis of autoimmune pancreatitis.

PMID- 24936579
TI  - Prognostic value of combined target-organ damage in patients with essential
      hypertension.
AB  - BACKGROUND: Whether the combination of chronic kidney disease (CKD) and left
      ventricular hypertrophy (LVH) affects the cardiovascular (CV) risk in patients
      with uncomplicated hypertension is poorly investigated. The aim of this study was
      to assess the effects of LVH, CKD, and their combination on CV events in
      hypertension. METHODS: This study analyzed 1,078 patients with essential
      hypertension. RESULTS: LVH was present in 104 (9.6%) patients, CKD was present in
      556 (51.5%) patients, and the combination of LVH and CKD was found in 174 (16.1%)
      patients. During the follow-up (median = 84 months), 52 CV events were observed
      (0.64 events/100 patient-years): 6 (2.4%) in patients without target-organ damage
      (TOD), 6 (5.7%) in patients with LVH, 20 (3.6%) in patients with CKD, and 20
      (11.4%) in patients with combined LVH+CKD. Adjusted hazard ratio (HR) for CV
      events was 1.62 (P = 0.34) for LVH, 0.951 (P = 0.94) for CKD, and 2.45 (P = 0.03)
      for LVH+CKD. After multivariable Cox proportional hazard analysis, the
      combination of LVH+CKD was significantly associated with risk of CV events, when
      the model was adjusted for sex and age (HR = 2.447; P = 0.03) and for the
      presence of 1 CV risk factor (HR = 3.226; P = 0.02). In contrast, the association
      of LVH+CKD was no longer significant when the model was adjusted for sex, age,
      and the presence of >= 2 CV risk factors. CONCLUSIONS: The results of this study
      highlight the relevance of the interactions between TODs and hemodynamic,
      anthropometric, and metabolic abnormalities in the CV risk stratification of
      patients with essential hypertension.

PMID- 24936580
TI  - Potential effect of skull thickening on the associations between cognition and
      brain atrophy in ageing.
AB  - BACKGROUND: intracranial volume (ICV) is commonly used as a marker of premorbid
      brain size in neuroimaging studies as it is thought to remain fixed throughout
      adulthood. However, inner skull table thickening would encroach on ICV and could
      mask actual brain atrophy. OBJECTIVE: we investigated the effect that thickening
      might have on the associations between brain atrophy and cognition. METHODS: the
      sample comprised 57 non-demented older adults who underwent structural brain MRI
      at mean age 72.7 +/- 0.7 years and were assessed on cognitive ability at mean age
      11 and 73 years. Principal component analysis was used to derive factors of
      general cognitive ability (g), information processing speed and memory from the
      recorded cognitive ability data. The total brain tissue volume and ICV with
      (estimated original ICV) and without (current ICV) adjusting for the effects of
      inner table skull thickening were measured. General linear modelling was used to
      test for associations. RESULTS: all cognitive ability variables were
      significantly (P < 0.01) associated with percentage total brain volume in ICV
      measured without adjusting for skull thickening (g: eta(2) = 0.177, speed: eta(2)
      = 0.264 and memory: eta(2) = 0.132). After accounting for skull thickening, only
      speed was significantly associated with percentage total brain volume in ICV
      (eta(2) = 0.085, P = 0.034), not g or memory. CONCLUSIONS: not accounting for
      skull thickening when computing ICV can distort the association between brain
      atrophy and cognitive ability in old age. Larger samples are required to
      determine the true effect.

PMID- 24936581
TI  - Screening tools for multidimensional health problems warranting a geriatric
      assessment in older cancer patients: an update on SIOG recommendations?.
AB  - BACKGROUND: Screening tools are proposed to identify those older cancer patients
      in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to
      update the International Society of Geriatric Oncology (SIOG) 2005
      recommendations on the use of screening tools. MATERIALS AND METHODS: SIOG
      composed a task group to review, interpret and discuss evidence on the use of
      screening tools in older cancer patients. A systematic review was carried out and
      discussed by an expert panel, leading to a consensus statement on their use.
      RESULTS: Forty-four studies reporting on the use of 17 different screening tools
      in older cancer patients were identified. The tools most studied in older cancer
      patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and
      Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity
      was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic
      Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult
      Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons
      for detecting problems on a full GA, the G8 was more or equally sensitive than
      other instruments in all six comparisons, whereas results were mixed for the VES
      13 in seven comparisons. In addition, different tools have demonstrated
      associations with outcome measures, including G8 and VES-13. CONCLUSIONS:
      Screening tools do not replace GA but are recommended in a busy practice in order
      to identify those patients in need of full GA. If abnormal, screening should be
      followed by GA and guided multidisciplinary interventions. Several tools are
      available with different performance for various parameters (including
      sensitivity for addressing the need for further GA). Further research should
      focus on the ability of screening tools to build clinical pathways and to predict
      different outcome parameters.

PMID- 24936583
TI  - Long-term T2 and Qualitative MRI Morphology After First-Generation Knee
      Autologous Chondrocyte Implantation: Cartilage Ultrastructure Is Not Correlated
      to Clinical or Qualitative MRI Outcome.
AB  - BACKGROUND: There are several reports on long-term clinical outcomes after
      autologous chondrocyte implantation (ACI) for knee cartilage defect treatment.
      Few published articles have evaluated defect quality using quantitative magnetic
      resonance (MR) imaging techniques. PURPOSE: To evaluate clinical outcomes and the
      quality of repair tissue (RT) after first-generation periosteum-covered ACI (ACI
      P) using qualitative MR outcomes and T2-weighted relaxation times. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: All patients (n = 86) who underwent
      knee joint ACI-P (from 1997 through 2001) with a postoperative follow-up of at
      least 10 years were invited for clinical and MR evaluation. Clinical outcomes
      analysis included pre- and postoperative Lysholm and numeric analog scale (NAS)
      for pain (10 = worst, 0 = best). Radiographic analysis included postoperative T2
      weighted mapping of the RT, RT-associated regions, and healthy control cartilage;
      MOCART (magnetic resonance observation of cartilage repair tissue) score; a
      modified Knee Osteoarthritis Scoring System (mKOSS; 0 = best, 15 = worst) score;
      as well as numeric grading for subjective RT and whole knee joint evaluation (1 =
      best, 6 = worst). RESULTS: A total of 70 patients (45 male, 25 female; mean age,
      33.3 +/- 10.2 years; 81% follow-up rate) with 82 defects were available for
      follow-up at an average 10.9 +/- 1.1 years postoperatively, with MR analysis for
      59 patients with 71 transplant sites (average defect size, 6.5 +/- 4.0 cm(2)).
      Final Lysholm (71.0 +/- 17.4) and NAS (7.2 +/- 1.9) scores improved significantly
      when compared with preoperative scores (Lysholm: 42.0 +/- 22.5; NAS: 2.1 +/- 2.1;
      P < .01 for both). Average transplant T2 was 35.2 +/- 11.3 ms and thereby
      significantly lower (P = .005) when compared to the intraknee healthy femur T2
      (39.7 +/- 6.8 ms). The MOCART was 44.9 +/- 23.6 and mKOSS was 4.8 +/- 3.2. RT
      subjective grading was 3.3 +/- 1.4, while it was 2.3 +/- 0.7 for whole joint
      evaluation. The RT T2 significantly correlated with postoperative NAS (P = .04; r
      = -0.28); it also correlated with the healthy femur T2 (P = .004; r = 0.4). The
      MOCART significantly correlated with the mKOSS (P < .001). CONCLUSION: The MRI
      outcome is imperfect in this collective of patients. There is only weak
      correlation of quantitative imaging data and clinical function. Qualitative
      imaging data are much better correlated to functional outcomes.

PMID- 24936582
TI  - Combined chemoradiotherapy with gemcitabine in patients with locally advanced
      inoperable transitional cell carcinoma of the urinary bladder and/or in patients
      ineligible for surgery: a phase I trial.
AB  - BACKGROUND: We conducted a phase I trial of gemcitabine (gem) with concurrent
      radiotherapy in patients with muscle-invasive bladder cancer (BC) ineligible for
      surgery or cisplatin or refusing organ loss. PATIENTS AND METHODS: Patients with
      urothelial cancer, cT2-T4, cN0-1, M0, ineligible for surgery due to local tumor
      extension, PS, age or co-morbidities or who refused surgery were included. After
      maximal transurethral resection, the treatment schedule included: twice-weekly
      i.v. infusion of gem [dose levels (DL) 1-6: 20, 27, 30, 33, 50 and 40 mg/m(2),
      respectively] for 30 min and concurrent radiotherapy (RT) to the bladder with
      55.5 Gy. The primary end point was to determine the maximum-tolerated dose (MTD)
      and the dose recommended (RD) for further studies of this gem schedule. The
      secondary end point was late toxicity. The MTD was defined by dose-limiting
      toxicity (DLT) in 2 or more of 6 patients, discontinuation of RT and/or gem for
      >1 week in 2 or more of 6 patients due to grade (G) 3/4 acute and/or late
      toxicity in more than 2 of 18 patients. RESULTS: Thirty-five of 44 patients were
      assessable for toxicity and thus the primary end point. DLTs occurred in two of
      five patients at dose level 5: one G3 alanine aminotransferase elevation and one
      G3 fatigue. The MTD, therefore, was 50 mg/m(2) gem twice weekly. At DL 6 with 40
      mg/m(2), the RD was established: only one of six patients developed G3 fatigue
      and diarrhea. Late toxicity was rare and of low grade (only G1-2). The 2-year
      locoregional failure rate was 32% (9/28); 10 of 28 patients (38%) were alive with
      an intact bladder and no evidence of recurrent disease, 9 patients developed
      distant metastases and 6 died of their disease. CONCLUSIONS: Gemcitabine in
      combination with RT is well tolerated in BC patients ineligible for surgery
      and/or cisplatin. The RD of gemcitabine for subsequent trials is 40 mg/m(2) twice
      weekly with concurrent radiation.

PMID- 24936584
TI  - Clinical Assessment of Physical Examination Maneuvers for Rotator Cuff Lesions.
AB  - BACKGROUND: Shoulder pain and disability pose a diagnostic challenge for
      clinicians owing to the numerous causes that exist. Unfortunately, the evidence
      in support of most clinical tests is weak or absent. PURPOSE: To determine the
      diagnostic validity of physical examination maneuvers for rotator cuff lesions.
      STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 1. METHODS:
      Consecutive shoulder patients recruited for this study were referred to 2
      tertiary orthopaedic clinics. A surgeon took a thorough history and indicated his
      or her certainty about each possible diagnosis. A clinician performed the
      physical examination for diagnoses where uncertainty remained. Arthroscopy was
      considered the reference standard for patients who underwent surgery, and MRI
      with arthrogram was considered the reference for patients who did not. The
      sensitivity, specificity, and likelihood ratios were calculated to investigate
      whether combinations of the top tests provided stronger predictions of the
      presence or absence of disease. RESULTS: There were 139 participants. None of the
      tests were highly sensitive for diagnosing rotator cuff tears or tendinosis.
      Tests for subscapularis tears were all highly specific. No optimal combination of
      tests improved the ability to correctly diagnose rotator cuff tears. Closer
      analysis revealed the internal rotation and lateral rotation lag sign did not
      improve the ability to diagnose subscapularis or supraspinatus tears,
      respectively, although the lateral rotation lag sign demonstrated a
      discriminatory ability for tear size. CONCLUSION: No test in isolation is
      sufficient to diagnose a patient with rotator cuff damage. A combination of tests
      improves the ability to diagnose damage to the rotator cuff. It is recommended
      that the internal rotation and lateral rotation lag signs be removed from the
      gamut of physical examination tests for supraspinatus and subscapularis tears.

PMID- 24936586
TI  - SPP1 rs9138 variant contributes to the severity of radiological damage in anti
      citrullinated protein autoantibody-negative rheumatoid arthritis.
AB  - OBJECTIVE: We recently reported an association of the SPP1 rs9138 and rs11439060
      functional variants with the risk of rheumatoid arthritis (RA), the association
      being greater in anti-citrullinated protein autoantibody (ACPA)-negative
      patients. We hypothesised that SPP1 may contribute to the severity of joint
      destruction in RA, specifically in the ACPA-negative population. METHODS:
      Patients with RA in the ESPOIR cohort underwent genotyping for SPP1 rs9138 and
      rs11439060. Radiographs of the hands and feet were obtained at the first visit
      and at 1- and 2-year follow-up. Association analyses were performed by ACPA
      status. A replication study of the relevant subset of the Leiden Early Arthritis
      Clinic (EAC) cohort was performed. RESULTS: In the ESPOIR cohort (652 patients),
      rs9138 was significantly associated with radiological progression of joint
      destruction at 2 years, the association being restricted to 358 ACPA-negative
      patients (p=0.034). In the replication study with the Leiden EAC cohort (273 ACPA
      negative patients), rs4754, which is in complete linkage disequilibrium with
      rs9138, was significantly associated with joint damage progression in ACPA
      negative patients at 2- and 7-year follow-up (p=0.019 and p=0.005, respectively).
      Combined analysis of the two cohorts revealed a 0.95-fold rate of joint
      destruction per year per minor allele (p=0.022). CONCLUSIONS: The SPP1 rs9138
      variant contributes to joint damage progression in ACPA-negative RA.

PMID- 24936587
TI  - A pharmaco-EEG-based assessment of the interaction between ethanol and
      zonisamide.
AB  - AIMS: Recent research suggests a potential role for a new generation of
      anticonvulsant drugs, including zonisamide, in the treatment of alcohol
      dependence. Some elements of the central mechanism of action that zonisamide has
      in common with ethanol, give rise to the question of whether there is an
      interaction between these two agents and whether there is any risk associated
      with the enhanced depressive effect of these agents on the central nervous
      system. METHODS: This study uses a pharmaco-EEG method to examine the interaction
      of ethanol with zonisamide. The influence of zonisamide on the effect of ethanol
      on EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex) was
      determined. Zonisamide was administered p.o. as a single dose (20 or 60 mg/kg) or
      repeatedly at a dose of 30 mg/kg/day for 14 days. Ethanol was injected i.v. at a
      dose of 0.8 g/kg 180 min after the administration of zonisamide. RESULTS: Ethanol
      caused an increase in the low frequencies (0.5-4 Hz) in the recording, as well as
      a marked decrease in the higher frequencies (13-30 and 30-45 Hz). Changes in the
      EEG recordings after zonisamide alone were more significant compared with these
      after repeated doses. In the hippocampus after single dose of drug the proportion
      of the low frequency (0.5-4 Hz) increased, whereas the proportion of high
      frequencies decreased. Combined administration of ethanol and zonisamide (60
      mg/kg) resulted in a markedly synergistic effect in the examined structures. A
      beneficial effect of repeatedly administered zonisamide on ethanol-induced EEG
      changes was observed, especially in the hippocampus. CONCLUSION: Zonisamide in
      repeated doses decreases the sensitivity of the hippocampus to ethanol, an
      observation that may be important in the treatment of alcohol addiction.

PMID- 24936585
TI  - Preclinical characterisation of the GM-CSF receptor as a therapeutic target in
      rheumatoid arthritis.
AB  - OBJECTIVE: Previous work has suggested that the granulocyte macrophage colony
      stimulating factor (GM-CSF)-GM-CSF receptor alpha axis (GM-CSFRalpha) may provide
      a new therapeutic target for the treatment of rheumatoid arthritis (RA).
      Therefore, we investigated the cellular expression of GM-CSFRalpha in RA synovial
      tissue and investigated the effects of anti-GM-CSFRalpha antibody treatment in
      vitro and in vivo in a preclinical model of RA. METHODS: We compared GM-CSFRalpha
      expression on macrophages positive for CD68 or CD163 on synovial biopsy samples
      from patients with RA or psoriatic arthritis (PsA) to disease controls. In
      addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a
      collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile
      of CAM-3003 was studied in naive CD1(ICR) mice (see online supplement) and used
      to interpret the results of the pharmacodynamic studies in BALB/c mice. RESULTS:
      GM-CSFRalpha was expressed by CD68 positive and CD163 positive macrophages in the
      synovium, and there was a significant increase in GM-CSFRalpha positive cells in
      patients in patients with RA as well as patients with PsA compared with patients
      with osteoarthritis and healthy controls. In the collagen induced arthritis model
      there was a dose dependent reduction of clinical arthritis scores and the number
      of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment.
      In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of
      peripheral blood monocytes and neutrophils. CONCLUSIONS: The findings support the
      ongoing development of therapies aimed at interfering with GM-CSF or its receptor
      in various forms of arthritis, such as RA and PsA.

PMID- 24936588
TI  - Translating the semi-structured assessment for drug dependence and alcoholism in
      the Western Pacific: rationale, study design and reliability of alcohol
      dependence.
AB  - AIMS: The aims of this study were to develop a bilingual version of the Semi
      Structured Assessment for Drug Dependence and Alcoholism (SSADDA) in English and
      Samoan and determine the reliability of assessments of alcohol dependence in
      American Samoa. METHODS: The study consisted of development and reliability
      testing phases. In the development phase, the SSADDA alcohol module was
      translated and the translation was evaluated through cognitive interviews. In the
      reliability-testing phase, the bilingual SSADDA was administered to 40 ethnic
      Samoans, including a sub-sample of 26 individuals who were retested. RESULTS:
      Cognitive interviews indicated the initial translation was culturally and
      linguistically appropriate except items pertaining to alcohol tolerance, which
      were modified to reflect Samoan concepts. SSADDA reliability testing indicated
      diagnoses of DSM-III-R and DSM-IV alcohol dependence were reliable. Reliability
      varied by language of administration. CONCLUSION: The English/Samoan version of
      the SSADDA is appropriate for the diagnosis of DSM-III-R alcohol dependence,
      which may be useful in advancing research and public health efforts to address
      alcohol problems in American Samoa and the Western Pacific. The translation
      methods may inform researchers translating diagnostic and assessment tools into
      different languages and cultures.

PMID- 24936589
TI  - Interactions between parental alcohol-specific rules and risk personalities in
      the prediction of adolescent alcohol use.
AB  - AIMS: To examine the impact of an important context variable (alcohol-specific
      parental rules) and an important person variable (risky personality traits) and
      their interaction on prospective adolescent drinking. METHODS: Participants were
      252 adolescents, 67.9% female, between 13 and 16 years old. Data were collected
      via online assessments during 2 years with four time points of assessments. We
      examined membership of alcohol use trajectories as a function of parental alcohol
      specific rules, moderated by risk-associated personality traits. RESULTS:
      Permissive parental rules predicted early onset and trajectories of heavy
      drinking. High scores on Sensation Seeking and Hopelessness also predicted early
      onset and heavy drinking, but there was no evidence for moderation. CONCLUSION:
      The influence of parental rule setting and risk personality was confirmed, but no
      evidence was found that the impact of risk personality on adolescent drinking is
      moderated by parental rules. Implications of these findings, and limitations of
      the study, are discussed.

PMID- 24936590
TI  - Sterilizing activity of thioridazine in combination with the first-line regimen
      against acute murine tuberculosis.
AB  - We recently reported that in lung tissue, thioridazine accumulates at high
      concentrations relative to serum levels, displaying modest synergy with isoniazid
      and reducing the emergence of isoniazid-resistant mutants in mouse lungs. In this
      study, we sought to investigate the sterilizing activity of human-equivalent
      doses of thioridazine when given in combination with the "Denver regimen" against
      acute murine tuberculosis. We found a trend toward a positive impact of
      thioridazine on the bacterial clearance and lowering relapse rates of the
      combined standard TB chemotherapy. 

PMID- 24936591
TI  - Efficacy of fosfomycin compared to vancomycin in treatment of implant-associated
      chronic methicillin-resistant Staphylococcus aureus osteomyelitis in rats.
AB  - Fosfomycin monotherapy was compared to therapy with vancomycin for the treatment
      of implant-associated methicillin-resistant Staphylococcus aureus (MRSA)
      osteomyelitis in an experimental rat model. The proximal tibiae were inoculated
      with 15 MUl of a suspension containing 1*10(8) to 5*10(8) CFU/ml of a clinical
      isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later,
      treatment was started for 28 days with either 50 mg/kg of body weight vancomycin
      intraperitoneally twice daily (n=11) or 75 mg/kg fosfomycin intraperitoneally
      once daily (n=10). Eleven animals were left untreated. After treatment,
      quantitative cultures from bone were found to be positive for MRSA in all animals
      in the untreated group (median, 3.29*10(6) CFU/g of bone) and the vancomycin
      group (median, 3.03*10(5) CFU/g of bone). In the fosfomycin group, MRSA was
      detectable in 2 out of 10 (20%) animals (3.42*10(2) and 1.51*10(3) CFU/g of
      bone). Vancomycin was superior to the no-drug control (P=0.002), and fosfomycin
      was superior to the no-drug control and vancomycin (P<0.001). The cultures from
      the wires were positive in all untreated animals (median, 2.5*10(3) CFU/implant),
      in 10 animals in the vancomycin group (median, 1.15*10(3) CFU/implant), and
      negative in all animals in the fosfomycin group. Based on the bacterial counts
      from the implants, vancomycin was not superior to the no-drug control (P=0.324),
      and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). No
      emergence of resistance was observed. In conclusion, it was demonstrated that
      fosfomycin monotherapy is highly effective for the treatment of experimental
      implant-associated MRSA osteomyelitis.

PMID- 24936592
TI  - Comparative mechanistic studies of brilacidin, daptomycin, and the antimicrobial
      peptide LL16.
AB  - Brilacidin (PMX30063) has shown potent bactericidal activity against drug
      resistant and -susceptible strains of multiple Gram-negative and Gram-positive
      pathogens. In this study, we demonstrate that brilacidin causes membrane
      depolarization in the Gram-positive bacterium Staphylococcus aureus, to an extent
      comparable to that caused by the lipopeptidic drug daptomycin. Transcriptional
      profiling of Staphylococcus aureus by deep sequencing shows that the global
      response to brilacidin treatment is well correlated to those of treatment with
      daptomycin and the cationic antimicrobial peptide LL37 and mostly indicates
      abrogation of cell wall and membrane functions. Furthermore, the upregulation of
      various chaperones and proteases by brilacidin and daptomycin indicates that
      cytoplasmic protein misfolding stress may be a contributor to the mechanism of
      action of these drugs. These stress responses were orchestrated mainly by three
      two-component systems, GraSR, VraSR, and NsaSR, which have been implicated in
      virulence and drug resistance against other clinically available antibiotics. 

PMID- 24936593
TI  - SAGA/ADA complex subunit Ada2 is required for Cap1- but not Mrr1-mediated
      upregulation of the Candida albicans multidrug efflux pump MDR1.
AB  - Overexpression of the multidrug efflux pump MDR1 is one mechanism by which the
      pathogenic yeast Candida albicans develops resistance to the antifungal drug
      fluconazole. The constitutive upregulation of MDR1 in fluconazole-resistant,
      clinical C. albicans isolates is caused by gain-of-function mutations in the zinc
      cluster transcription factor Mrr1. It has been suggested that Mrr1 activates MDR1
      transcription by recruiting Ada2, a subunit of the SAGA/ADA coactivator complex.
      However, MDR1 expression is also regulated by the bZIP transcription factor Cap1,
      which mediates the oxidative stress response in C. albicans. Here, we show that a
      hyperactive Mrr1 containing a gain-of-function mutation promotes MDR1
      overexpression independently of Ada2. In contrast, a C-terminally truncated,
      hyperactive Cap1 caused MDR1 overexpression in a wild-type strain but only weakly
      in mutants lacking ADA2. In the presence of benomyl or H2O2, compounds that
      induce MDR1 expression in an Mrr1- and Cap1-dependent fashion, MDR1 was
      upregulated with the same efficiency in wild-type and ada2Delta cells. These
      results indicate that Cap1, but not Mrr1, recruits Ada2 to the MDR1 promoter to
      induce the expression of this multidrug efflux pump and that Ada2 is not required
      for MDR1 overexpression in fluconazole-resistant C. albicans strains containing
      gain-of-function mutations in Mrr1. 

PMID- 24936594
TI  - Pharmacokinetics and preliminary safety study of pod-intravaginal rings
      delivering antiretroviral combinations for HIV prophylaxis in a macaque model.
AB  - Preexposure prophylaxis using oral regimens involving the HIV nucleoside reverse
      transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine
      (FTC) demonstrated efficacy in three clinical trials. Adherence was determined to
      be a key parameter for success. Incorporation of the TDF-FTC combination into
      intravaginal rings (IVRs) for sustained mucosal delivery could increase product
      adherence and efficacy compared with those of oral and vaginal gel formulations.
      A novel pod-IVR technology capable of delivering multiple drugs is described;
      this constitutes the first report of an IVR delivering TDF and FTC, as well as a
      triple-combination IVR delivering TDF, FTC, and the entry inhibitor maraviroc
      (MVC). The pharmacokinetics and preliminary local safety of the two combination
      pod-IVRs were evaluated in the pig-tailed macaque model. The devices exhibited
      sustained release at controlled rates over the 28-day study period. Median steady
      state drug levels in vaginal tissues in the TDF-FTC group were 30 MUg g(-1)
      (tenofovir [TFV], in vivo hydrolysis product of TDF) and 500 MUg g(-1) (FTC) and
      in the TDF-FTC-MVC group were 10 MUg g(-1) (TFV), 150 MUg g(-1) (FTC), and 20 MUg
      g(-1) (MVC). No adverse events were observed, and there were no toxicological
      findings. Mild-to-moderate increases in inflammatory infiltrates were observed in
      the vaginal tissues of some animals in both the presence and the absence of the
      IVRs. The IVRs did not disturb the vaginal microbiota, and levels of
      proinflammatory cytokines remained stable throughout the study. Pod-IVR
      candidates based on the TDF-FTC combination have potential for the prevention of
      vaginal HIV acquisition and merit clinical investigation. 

PMID- 24936595
TI  - First detection of TR46/Y121F/T289A and TR34/L98H alterations in Aspergillus
      fumigatus isolates from azole-naive patients in Denmark despite negative findings
      in the environment.
AB  - Azole-resistant Aspergillus fumigatus harboring the TR34/L98H or TR46/Y121F/T289A
      alterations is increasingly found in Europe and Asia. Here, we present the first
      clinical cases of TR46/Y121/T289A and three cases of TR34/L98H outside the cystic
      fibrosis (CF) population in Denmark and the results of environmental surveys.
      Four patients (2012 to 2014) with 11 A. fumigatus and 4 Rhizomucor pusillus
      isolates and 239 soil samples (spring 2010 and autumn 2013, respectively) with a
      total of 113 A. fumigatus isolates were examined. Aspergillus isolates were
      screened for azole resistance using azole-containing agar. Confirmatory
      susceptibility testing was done using the EUCAST microbroth dilution EDEF 9.1
      reference method. For relevant A. fumigatus isolates, CYP51A sequencing and
      microsatellite genotyping were performed. Three patients harbored TR34/L98H
      isolates. Two were azole naive at the time of acquisition and two were coinfected
      with wild-type A. fumigatus or R. pusillus isolates, complicating and delaying
      diagnosis. The TR46/Y121F/T289A strain was isolated in 2014 from a lung
      transplant patient. Genotyping indicated that susceptible and resistant
      Aspergillus isolates were unrelated and that no transmission between patients
      occurred. Azole resistance was not detected in any of the 113 soil isolates.
      TR34/L98H and TR46/Y121F/T289A alterations appear to be emerging in the clinical
      setting in Denmark and now involve azole-naive patients. Two recent soil-sampling
      surveys in Denmark were unable to indicate any increased prevalence of azole
      resistant A. fumigatus in the environment. These findings further support the
      demand for real-time susceptibility testing of all clinically relevant isolates
      and for studies investigating the seasonal variation and ecological niches for
      azole-resistant environmental A. fumigatus.

PMID- 24936596
TI  - Comparison of cefazolin versus oxacillin for treatment of complicated bacteremia
      caused by methicillin-susceptible Staphylococcus aureus.
AB  - Contrary to prior case reports that described occasional clinical failures with
      cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections,
      recent studies have demonstrated no difference in outcomes between cefazolin and
      antistaphylococcal penicillins for the treatment of MSSA bacteremia. While
      promising, these studies described low frequencies of high-inoculum infections,
      such as endocarditis. This retrospective study compares clinical outcomes of
      cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care
      hospitals between January 2008 and June 2012. Fifty-nine patients treated with
      cefazolin and 34 patients treated with oxacillin were included. Osteoarticular
      (41%) and endovascular (20%) sources were the predominant sites of infection. The
      rates of clinical cure at the end of therapy were similar between cefazolin and
      oxacillin (95% versus 88%; P=0.25), but overall failure at 90 days was higher in
      the oxacillin arm (47% versus 24%; P=0.04). Failures were more likely to have
      received surgical interventions (63% versus 40%; P=0.05) and to have an
      osteoarticular source (57% versus 33%; P=0.04). Failures also had a longer
      duration of bacteremia (7 versus 3 days; P=0.0002), which was the only predictor
      of failure. Antibiotic selection was not predictive of failure. Rates of adverse
      drug events were higher in the oxacillin arm (30% versus 3%; P=0.0006), and
      oxacillin was more frequently discontinued due to adverse drug events (21% versus
      3%; P=0.01). Cefazolin appears similar to oxacillin for the treatment of
      complicated MSSA bacteremia but with significantly improved safety. The higher
      rates of failure with oxacillin may have been confounded by other patient factors
      and warrant further investigation.

PMID- 24936597
TI  - Decreasing Clostridium difficile infections by an antimicrobial stewardship
      program that reduces moxifloxacin use.
AB  - Clostridium difficile infections (CDI) in hospitalized patients are known to be
      closely related to antibiotic exposure. Although several substances can cause
      CDI, the risk differs between individual agents. In Vienna and other eastern
      parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype
      has the characteristic of intrinsic moxifloxacin resistance. Therefore, we
      hypothesized that moxifloxacin restriction can decrease the number of CDI cases
      in hospitalized patients. Our antibiotic stewardship (ABS) group applied an
      information campaign on CDI and formal restriction of moxifloxacin in
      Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The
      preintervention period (period 1) was January through May 2013, and the
      intervention period (period 2) was June through December 2013. We recorded the
      defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month.
      Moxifloxacin use was reduced from a mean (+/-standard error of the mean [SEM]) of
      1,038+/-109 DDD per month (period 1) to 42+/-10 DDD per month (period 2)
      (P=0.0045). Total antibiotic use was not affected. The mean (+/-SEM) numbers of
      CDI cases in period 1 were 59+/-3 per month and in period 2 were 32+/-3 per month
      (46% reduction; P=0.0044). Reducing moxifloxacin use in combination with
      providing structured information on CDI was associated with an immediate decrease
      in CDI rates in this large community teaching hospital.

PMID- 24936599
TI  - The Pseudomonas aeruginosa CreBC two-component system plays a major role in the
      response to beta-lactams, fitness, biofilm growth, and global regulation.
AB  - Pseudomonas aeruginosa is a ubiquitous versatile environmental microorganism with
      a remarkable ability to grow under diverse environmental conditions. Moreover, P.
      aeruginosa is responsible for life-threatening infections in immunocompromised
      and cystic fibrosis patients, as the extraordinary capacity of this pathogen to
      develop antimicrobial resistance dramatically limits our therapeutic arsenal. Its
      large genome carries an outstanding number of genes belonging to regulatory
      systems, including multiple two-component sensor-regulator systems that modulate
      the response to the different environmental stimuli. Here, we show that one of
      two systems, designated CreBC (carbon source responsive) and BlrAB (beta-lactam
      resistance), might be of particular relevance. We first identified the stimuli
      triggering the activation of the CreBC system, which specifically responds to
      penicillin-binding protein 4 (PBP4) inhibition by certain beta-lactam
      antibiotics. Second, through an analysis of a large comprehensive collection of
      mutants, we demonstrate an intricate interconnection between the CreBC system,
      the peptidoglycan recycling pathway, and the expression of the concerning
      chromosomal beta-lactamase AmpC. Third, we show that the CreBC system, and
      particularly its effector inner membrane protein CreD, plays a major role in
      bacterial fitness and biofilm development, especially in the presence of
      subinhibitory concentrations of beta-lactams. Finally, global transcriptomics
      reveals broad regulatory functions of CreBC in basic physiological aspects,
      particularly anaerobic respiration, in both the presence and absence of
      antibiotics. Therefore, the CreBC system is envisaged as a potentially
      interesting target for improving the efficacy of beta-lactams against P.
      aeruginosa infections. 

PMID- 24936602
TI  - News, views, & reviews: antimicrobial photodynamic therapy: applications beyond
      skin cancer.

PMID- 24936598
TI  - In vitro and in vivo effects of tamoxifen against larval stage Echinococcus
      granulosus.
AB  - Cystic echinococcosis is a zoonotic infection caused by the larval stage of the
      cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles;
      however, 40% of cases do not respond favorably. With regard to these
      difficulties, novel therapeutic tools are needed to optimize treatment in humans.
      The aim of this work was to explore the in vitro and in vivo effects of tamoxifen
      (TAM) against E. granulosus. In addition, possible mechanisms for the
      susceptibility of TAM are discussed in relation to calcium homeostasis, P
      glycoprotein inhibition, and antagonist effects on a putative steroid receptor.
      After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50
      MUM), inhibited the survival of E. granulosus protoscoleces and metacestodes.
      Moreover, we demonstrated the chemotherapeutic and chemopreventive
      pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight,
      TAM induced protection against the infection in mice. In the clinical efficacy
      studies, a reduction in cyst weight was observed after the administration of 20
      mg/kg in mice with cysts developed during 3 or 6 months, compared to that of
      those collected from control mice. Since the collateral effects of high TAM doses
      have been largely documented in clinical trials, the use of low doses of this
      drug as a short-term therapy may be a novel alternative approach for human cystic
      echinococcosis treatment. 

PMID- 24936603
TI  - Preface. Pseudomonas methods and protocols.

PMID- 24936600
TI  - Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus
      genotypes 1 to 6: implications for cross-genotype activity.
AB  - A comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on
      authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV)
      genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay.
      The data indicated that genotype 1b (GT-1b) has the highest relative resistance
      barrier and genotype 2a (GT-2a M31) has the lowest. The rank order of resistance
      barriers to DCV was 1b>4a>=5a>6a?1a>2a JFH>3a>2a M31. Importantly, DCV in
      combination with a protease inhibitor (PI) eliminated GT-2a M31 replicon RNA at a
      clinically relevant concentration. Previously, we reported the antiviral activity
      and resistance profiles of DCV on HCV genotypes 1 to 4 evaluated in the replicon
      system. Here, we report the antiviral activity and resistance profiles of DCV
      against hybrid replicons with NS5A sequences derived from HCV GT-5a and GT-6a
      clinical isolates. DCV was effective against both GT-5a and -6a hybrid replicon
      cell lines (50% effective concentrations [EC50s] ranging from 3 to 7 pM for GT
      5a, and 74 pM for GT-6a). Resistance selection identified amino acid
      substitutions in the N-terminal domain of NS5A. For GT-5a, L31F and L31V, alone
      or in combination with K56R, were the major resistance variants (EC50s ranging
      from 2 to 40 nM). In GT-6a, Q24H, L31M, P32L/S, and T58A/S were identified as
      resistance variants (EC50s ranging from 2 to 250 nM). The in vitro data suggest
      that DCV has the potential to be an effective agent for HCV genotypes 1 to 6 when
      used in combination therapy.

PMID- 24936604
TI  - Biocultural implications of oral pathology in an ancient Central California
      population.
AB  - Bioarchaeologists have long noted two unusual trends in the dentitions of
      prehistoric Native Californian populations: high rates of wear and low prevalence
      of caries. The Central California site of CA-CCO-548 offers a unique opportunity
      to examine the relationship between oral pathology and extreme dental wear in a
      large (n = 480), ancient (4,300-3,100 BP), and temporally well-defined population
      sample. This study specifically examines three interrelated processes of the oral
      cavity in this population: dental wear, dental caries, and periodontal disease.
      The results show high levels of dental wear (average of 6.1, Smith system), low
      frequencies of carious lesions (2.5%), low frequencies of periodontal disease
      (17.8%), and high frequencies of periapical abscesses (10.7%). The pathological
      processes examined here have complicated multifactorial etiologies. However, they
      all share the common primary etiological agents of facultative pathogenic
      bacteria proliferation in the oral biofilm. Integration of the current
      etiological explanations for infections of the oral cavity, information from the
      ethnographic record pertaining to subsistence and activity patterns in Native
      Californian populations, and statistical analysis of specific disease and wear
      patterns leads to a novel explanation for the observed pattern of oral pathology
      in this population sample. Specifically, the introduction of antibacterial
      compounds through dietary items and non-alimentary tooth use is suggested as the
      most likely explanation for the unusually low prevalence of dental caries and
      periodontal disease.

PMID- 24936606
TI  - Health Is not always written in bone: using a modern comorbidity index to assess
      disease load in paleopathology.
AB  - Paleopathology has revealed much about disease in the past but is usually limited
      to conditions with osteological manifestations; this often excludes acute soft
      tissue infections and causes of death for most individuals in the past and
      present. Our understanding of the evolution of disease is essential for
      contextualizing and predicting the epidemiological shifts that are happening in
      modern society, as high rates of infectious disease coexist alongside high rates
      of chronic disease in rates unlike those observed previously in human history.
      Moreover, many physiological states not previously classified as "disease"
      (obesity) have become pathologized, influencing our conception of disease and
      what defines health. By using the Galler Collection, a pre-antibiotic and pre
      chemotherapeutic osteological series with modern autopsy records, our research
      quantifies disease burden of the past using the Charlson Index (CI), a modern
      comorbidity index of disease severity. Galler Collection remains and autopsy
      records were scored with the Charlson Index to correlate bone findings with soft
      tissue findings, and statistical analysis was performed for cumulative scores and
      absolute diagnosis counts, with patients stratified by sex and cause of death
      (pneumonia or cancer). Osteological diagnosis counts were more predictive of soft
      tissue autopsy disease counts than were associated cumulative CI scores.
      Diagnosis counts and CI scores for osteological data were more closely related to
      associated soft tissue data for cancer patients than for pneumonia patients. This
      research indicates how interdisciplinary paleopathological analysis assists in
      making more reliable assessments of health and mortality in the past, with
      implications for trending and predicting future epidemiological shifts.

PMID- 24936605
TI  - Genetic influences on the development of grip strength in adolescence.
AB  - Enhanced physical strength is a secondary sex characteristic in males. Sexual
      dimorphism in physical strength far exceeds sex differences in stature or total
      body mass, suggesting a legacy of intense sexual selection. Upper-body strength
      is a particularly promising marker of intrasexual competitiveness in young men.
      Consequently, it is assumed that sex-influenced gene expression contributes to
      the development of physical strength. It is unclear, however, whether the
      underlying sources of individual differences in strength development are
      comparable across sex. We obtained three measurements of hand-grip strength (HGS)
      over a six-year period spanning adolescence in male and female same-sex twins (N
      = 2,513). Biometrical latent growth models were used to partition the HGS
      variance at age 11 (intercept) and its growth over time (slope) into genetic and
      environmental components. Results demonstrated that variance around the intercept
      was highly heritable in both males and females (88% and 79%, respectively). In
      males, variance around the slope exceeded that of the intercept, while the
      reverse held for females. Additive genetic effects accounted for most (80%) of
      the variance around the slope in males, but were of less importance in females
      (heritability = 28%). Absolute genetic variance around the slope was nearly nine
      fold higher in males. This striking disparity suggests that the developmental
      processes shaping HGS growth are different between the sexes. We propose that
      this might account for the sex-specific pattern of associations between HGS and
      external measures (e.g., digit ratio and physical aggression) typically reported
      in the literature. Our results underscore the role of endogenous androgenic
      influences in the development of physical strength.

PMID- 24936607
TI  - Developing a pig model for crypt fenestration-induced localized hypoplastic
      enamel defects in humans.
AB  - Hypoplastic pits on human deciduous canine teeth are attributed to nutritionally
      induced thinning of the crypt wall prior to eruption, exposing ameloblasts to
      unspecified physical trauma through the fenestration. Traditionally known as
      localized hypoplasia of the primary canine (LHPC), this little-understood
      condition is reported in fields ranging from public health to bioarchaeology. We
      propose the defect be termed a 'crypt fenestration hypoplastic enamel defect'
      (CFED) to reflect that an analogous lesion is created postnatally on maxillary
      molars of pigs. Pigs are accepted as a suitable proxy for many studies in human
      biology. We compare fenestration defects and CFEDs between 50 Sick Pen pigs, who
      died naturally, and 20 Controls. Observations were made of the presence, number
      and size of fenestrations in molar crypts. CFEDs were counted on erupted
      deciduous last molars and permanent first molars. Signs of being underweight and
      cranio-dental infection at death were recorded. Sick pen pigs show significantly
      more fenestrations at death and CFEDs acquired before death. These conditions co
      occur with infection and poor growth. The deep fibers of temporalis muscle lie
      adjacent to the crypt wall of maxillary molars. We propose that contraction of
      this muscle during suckling and chewing creates large compressive forces against
      fenestrated bony surfaces sufficient to have physiological consequences for
      physically unprotected ameloblasts. While we conclude that a pig model is
      appropriate to study fenestration-induced enamel defects, this naturalistic
      experiment leaves unresolved whether osteopenia in pigs, and by extension in
      human infants, is due to disease and/or malnutrition.

PMID- 24936608
TI  - In Memoriam. Obituary: Professor Andrea  Mezzetti, MD (1949-2013).

PMID- 24936610
TI  - Referential labeling can facilitate phonetic learning in infancy.
AB  - All languages employ certain phonetic contrasts when distinguishing words. Infant
      speech perception is rapidly attuned to these contrasts before many words are
      learned, thus phonetic attunement is thought to proceed independently of lexical
      and referential knowledge. Here, evidence to the contrary is provided. Ninety
      eight 9-month-old English-learning infants were trained to perceive a non-native
      Cantonese tone contrast.Two object-tone audiovisual pairings were consistently
      presented, which highlighted the target contrast (Object A with Tone X; Object B
      with Tone Y). Tone discrimination was then assessed. Results showed improved tone
      discrimination if object-tone pairings were perceived as being referential word
      labels, although this effect was modulated by vocabulary size. Results suggest
      how lexical and referential knowledge could play a role in phonetic attunement.

PMID- 24936609
TI  - Adult attachment states of mind: measurement invariance across ethnicity and
      associations with maternal sensitivity.
AB  - This study examined the developmental significance of mothers' adult attachment
      representations assessed prenatally with the Adult Attachment Interview in
      relation to observed maternal sensitivity at 6 months postpartum in an ethnically
      diverse sample (N = 131 African American; N = 128 European American). Multiple
      group confirmatory factor analyses provided evidence for partial measurement
      invariance of a two-factor dismissing and preoccupied latent structure of adult
      attachment across the two ethnic groups of women. African American women showed
      modest elevations on the preoccupied factor relative to European American women.
      Although the dismissing factor showed an empirically equivalent negative
      association with maternal sensitivity in both ethnic groups, this effect was
      reduced to marginal significance when controlling for maternal socioeconomic
      status.

PMID- 24936611
TI  - Judgments and reasoning about parental discipline involving induction and
      psychological control in China and Canada.
AB  - This study examined judgments and reasoning about four parental discipline
      practices (induction or reasoning and three practices involving "psychological
      control"; Barber, 1996; two forms of shaming and love withdrawal)among children
      (7-14 years of age) from urban and rural China and Canada (N = 288) in response
      to a moral transgression. Children from all settings critically evaluated love
      withdrawal and preferred induction. Despite being perceived as more common in
      China than in Canada, with age, parental discipline based on shaming or love
      withdrawal was increasingly negatively evaluated and believed to have detrimental
      effects on children's feelings of self-worth and psychological well-being. Some
      cultural variations were found in evaluations of practices, perceptions of
      psychological harm, and attribution of parental goals.

PMID- 24936612
TI  - Children's social self-concept and internalizing problems: the influence of peers
      and teachers.
AB  - This study aimed to understand how relationships with peers and teachers
      contribute to the development of internalizing problems via children's social
      self-concept. The sample included 570 children aged 7 years 5 months (SD = 4.6
      months). Peer nominations of peer rejection, child-reported social self-concept,
      and teacher-reported internalizing problems were assessed longitudinally in the
      fall and spring of Grades 2 and 3. Teacher reports of support to the child were
      assessed in Grade 2. Results showed that peer rejection impeded children's social
      self-concept, which in turn affected the development of internalizing problems.
      Partial support was found for individual (but not classroom-level) teacher
      support to buffer the adverse effects of peer problems on children's self
      concept, thereby mitigating its indirect effects on internalizing problems.

PMID- 24936613
TI  - Children's reasoning about the refusal to help: the role of need, costs, and
      social perspective taking.
AB  - Children (n = 133, aged 8-13) were interviewed about helping situations that
      systematically varied in recipient's need for help and the costs for the helper.
      In situations where helping a peer involved low costs, children perceived a moral
      obligation to help that was independent of peer norms, parental authority, and
      reciprocity considerations. When helping a peer involved high costs this over
      powered the perceived obligation to help, but only in situations involving low
      need and when in line with reciprocity. When both need and costs were high,
      younger children expressed stronger moral indignation while older children were
      less negative and reasoned in terms of other solutions. Furthermore, stronger
      moral indignation was related to more advanced social perspective taking skills
      when need and costs were high.

PMID- 24936615
TI  - [Arthroplasty].

PMID- 24936614
TI  - Dr Cai and colleagues respond.

PMID- 24936616
TI  - Robo3.1A suppresses slit-mediated repulsion by triggering degradation of Robo2.
AB  - Slits and Robos control the midline crossing of commissural axons, which are not
      sensitive to the midline repellent Slit before crossing but gain Slit
      responsiveness to exit the midline and avoid recrossing. Robo3.1A promotes
      midline crossing of commissural axons by suppressing the axonal responsiveness to
      the midline repellent Slit, but the underlying mechanism remains unclear. By
      using a cell surface binding assay and immunoprecipitation, we observed that
      Robo3.1A did not bind Slit on its own but prevented the specific binding of Slit
      to the cell surface when it was coexpressed with its close homologue Robo1 or
      Robo2 (Robo1/2), which are known to mediate the Slit repulsion. Cotransfection
      with Robo3.1A significantly reduced the protein level of Robo2 in HEK293 cells,
      and overexpression of Robo3.1A also significantly decreased Robo2 protein level
      in cerebellar granule cells. Downregulation of endogenous Robo3 by specific small
      interference RNA (siRNA) significantly increased Robo1 protein level, Slit
      binding to the cell surface was significantly elevated, and Slit-triggered growth
      cone collapse appeared after downregulation of Robo3 in cultured cortical
      neurons. Immunocytochemical staining showed that Robo2 and Robo3 colocalized in
      intracellular vesicles positive for the marker of late endosomes and lysosomes,
      but not trans-Golgi apparatus and early endosomes. Thus Robo3.1A may prevent the
      Slit responsiveness by recruiting Robo1/2 into a late endosome- and lysosome
      dependent degradation pathway.

PMID- 24936618
TI  - Multiferroic polymer composites with greatly enhanced magnetoelectric effect
      under a low magnetic bias.
AB  - Multiferroic laminate composites consisting of chain-end cross-linked
      ferroelectric polymers and magnetostrictive Metglas are reported. The composites
      exhibit a greatly enhanced multiferroic voltage coefficient and sensitivity
      relative to analogous composites. These remarkable properties are attributed to
      high piezoelectric and electromechanical coupling coefficients, because of the
      formation of larger crystalline sizes and concurrent improvement in the
      polarization ordering in the cross-linked polymers.

PMID- 24936617
TI  - Stem cell factor-activated bone marrow ameliorates amyotrophic lateral sclerosis
      by promoting protective microglial migration.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with
      motor neuron death. Several experimental treatments, including cell therapy using
      hematopoietic or neuronal stem cells, have been tested in ALS animal models, but
      therapeutic benefits have been modest. Here we used a new therapeutic strategy,
      bone marrow transplantation (BMT) with stem cell factor (SCF)- or FMS-like
      tyrosine kinase 3 (flt3)-activated bone marrow (BM) cells for the treatment of
      hSOD1(G93A) transgenic mice. Motor function and survival showed greater
      improvement in the SCF group than in the group receiving BM cells that had not
      been activated (BMT alone group), although no improvement was shown in the flt3
      group. In addition, larger numbers of BM-derived cells that expressed the
      microglia marker Iba1 migrated to the spinal cords of recipient mice compared
      with the BMT alone group. Moreover, after SCF activation, but not flt3 activation
      or no activation, the migrating microglia expressed glutamate transporter-1 (GLT
      1). In spinal cords in the SCF group, inflammatory cytokines tumor necrosis
      factor-alpha and interleukin-1beta were suppressed and the neuroprotective
      molecule insulin-like growth factor-1 increased relative to nontreatment
      hSOD1(G93A) transgenic mice. Therefore, SCF activation changed the character of
      the migrating donor BM cells, which resulted in neuroprotective effects. These
      studies have identified SCF-activated BM cells as a potential new therapeutic
      agent for the treatment of ALS.

PMID- 24936619
TI  - Low-dose total-body carbon-ion irradiations induce early transcriptional
      alteration without late Alzheimer's disease-like pathogenesis and memory
      impairment in mice.
AB  - The cause and risk factors of Alzheimer's disease (AD) are largely unknown.
      Studies on possible radiation-induced AD-like pathogenesis and behavioral
      consequences are important because humans are exposed to ionizing radiation (IR)
      from various sources. It was reported that total-body irradiations (TBI) at 10
      cGy of low linear energy transfer (LET) X-rays to mice triggered acute
      transcriptional alterations in genes associated with cognitive dysfunctions.
      However, it was unknown whether low doses of IR could induce AD-like changes late
      after exposure. We reported previously that 10 cGy X-rays induced early
      transcriptional response of several AD-related genes in hippocampi without late
      AD-like pathogenesis and memory impairment in mice. Here, further studies on two
      low doses (5 or 10 cGy) of high LET carbonion irradiations are reported. On
      expression of 84 AD-related genes in hippocampi, at 4 hr after TBI, 5 cGy induced
      a significant upregulation of three genes (Abca1, Casp3, and Chat) and 10 cGy led
      to a marked upregulation of one gene (Chat) and a downregulation of three genes
      (Apoe, Ctsd, and Il1alpha), and, at 1 year after TBI, one gene (Il1alpha) was
      significantly downregulated in 10 cGy-irradiated animals. Changes in spatial
      learning ability and memory and induction of AD-like pathogenesis were not
      detected by in vivo brain imaging for amyloid-beta peptide accumulation and by
      immunohistochemical staining of amyloid precursor protein, amyloid-beta protein,
      tau, and phosphorylated tau protein. These findings indicate that low doses of
      carbon-ion irradiations did not cause behavioral impairment or AD-like
      pathological change in mice.

PMID- 24936620
TI  - Author response.

PMID- 24936621
TI  - Author response.

PMID- 24936622
TI  - America embraces treatment for opioid drug overdose.

PMID- 24936623
TI  - Ending sexual violence in conflict and beyond.

PMID- 24936624
TI  - Disease outbreaks predicted in flood-ravaged Balkans.

PMID- 24936625
TI  - Responding to sexual violence in armed conflict.

PMID- 24936626
TI  - Uganda takes "another step backward" with HIV bill.

PMID- 24936627
TI  - The challenges of research on violence in post-conflict Bougainville.

PMID- 24936628
TI  - Unnatural reactions.

PMID- 24936629
TI  - Douglas Leonard Coleman.

PMID- 24936630
TI  - Venezuela: violence,   human rights, and   health-care realities.

PMID- 24936631
TI  - [Message from the Historian of the Interamerican Society of  Cardiology].

PMID- 24936632
TI  - [In memoriam of my friend Fause Attie].

PMID- 24936633
TI  - [Fause Attie. On his transcendent performance in studying and managing congenital
      cardiopathies in Mexico].

PMID- 24936634
TI  - [Extended spectrum beta-lactamase-producing Enterobacteriaceae].

PMID- 24936635
TI  - [Prevention of catheter-related sepsis].

PMID- 24936637
TI  - 25 largest master's programs in health administration ranked by total full-time
      enrollment in 2013-14 academic year.

PMID- 24936636
TI  - Improving services for older people.

PMID- 24936638
TI  - Be prepared for when surveyors come knocking.

PMID- 24936639
TI  - Better data highlight: growing problem.

PMID- 24936640
TI  - 'Be prepared to provide high value'.

PMID- 24936641
TI  - Largest physician staffing firms: Ranked by number of physician recruiters as of
      March 2014.

PMID- 24936643
TI  - Paradoxical exploitation of protected fishes as bait for anglers: evaluating the
      Lamprey bait market in Europe and developing sustainable and ethical solutions.
AB  - A reoccurring conservation problem is the resolution of consumptive use of
      threatened wildlife and is especially difficult to defend when it occurs for
      recreational practices. We explored the commercial capture and supply of
      threatened European river lamprey (Lampetra fluviatilis) to anglers, to determine
      the extent of exploitation and seek opportunities for improved conservation. The
      trade began in 1995 from England, but by 2012 involved sale of lamprey from
      England, The Netherlands and Estonia, including from protected populations.
      Lamprey are sold frozen for the capture of predatory fish, mostly in freshwater.
      In the year 2011/2012 9 tonnes (>90,000 lampreys) of river lamprey were supplied,
      almost exclusively to British anglers. Although annual catches in the main
      English lamprey fishery (River Ouse) have varied widely since 1995, catch per
      unit effort did not decline between 2000 and 2012. Conservation actions since
      2011 have included a cap on fishing licenses, catch quotas and restricted fishing
      seasons. Now, 86% of lamprey bait is imported to Britain. Most bait sellers
      interviewed would not stock lamprey if they knew they were from threatened
      populations; many felt their trade would not be impacted if lamprey were not
      stocked. This facilitates opportunities to enter into dialogue with anglers over
      alternative baits to threatened lamprey. The study emphasises the need to inform
      stakeholders about conservation species subjected to market-driven exploitation. 

PMID- 24936644
TI  - Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil.
AB  - Germline TP53 mutations predispose individuals to multiple cancers and are
      associated with Li-Fraumeni/Li-Fraumeni-Like Syndromes (LFS/LFL). The founder
      mutation TP53 p.R337H is detected in 0.3% of the general population in southern
      Brazil. This mutation is associated with an increased risk of childhood adrenal
      cortical carcinoma (ACC) but is also common in Brazilian LFS/LFL families. Breast
      Cancer (BC) is one of the most common cancers diagnosed in TP53 mutation
      carriers. We have assessed the prevalence of p.R337H in two groups: (1) 59 BC
      affected women with a familial history (FH) suggestive of hereditary cancer
      syndrome but no LFS/LFL features; (2) 815 BC affected women unselected for cancer
      FH, diagnosed with BC at or before age 45 or at age 55 or older. Among group 1
      and group 2 patients, 2/59 (3.4%, CI95%: 0.4%-11.7%) and 70/815 (8.6%, CI95%:
      6.8%-10.7%), respectively, were p.R337H carriers in the germline. The prevalence
      of p.R337H was higher in women diagnosed with BC at or before age 45 (12.1%,
      CI95%: 9.1%-15.8%) than at age 55 or older (5.1%, CI95%: 3.2%-7.7%), p<0.001).
      The Brazilian founder p.R337H haplotype was detected in all carriers analysed.
      These results suggest that inheritance of p.R337H may significantly contribute to
      the high incidence of BC in Brazil, in addition to its recently demonstrated
      impact on the risk of childhood ACC. 

PMID- 24936645
TI  - Association between DNMT3A mutations and prognosis of adults with de novo acute
      myeloid leukemia: a systematic review and meta-analysis.
AB  - BACKGROUND: DNA methyltransferase 3A (DNMT3A) mutations were considered to be
      independently associated with unfavorable prognosis in adults with de novo acute
      myeloid leukemia (AML), however, there are still debates on this topic. Here, we
      aim to further investigate the association between DNMT3A mutations and prognosis
      of patients with AML. METHODS: Eligible studies were identified from several data
      bases including PubMed, Embase, Web of Science, ClinicalTrials and the Cochrane
      Library (up to June 2013). The primary endpoint was overall survival (OS), while
      relapse-free survival (RFS) and event-free survival (EFS) were chosen as
      secondary endpoints. If possible, we would pool estimate effects (hazard ratio
      [HR] with 95% confidence interval[CI]) of outcomes in random and fixed effects
      models respectively. RESULTS: That twelve cohort studies with 6377 patients
      exploring the potential significance of DNMT3A mutations on prognosis were
      included. Patients with DNMT3A mutations had slightly shorter OS (HR = 1.60; 95%
      CI, 1.31-1.95; P<0.001), as compared to wild-type carriers. Among the patients
      younger than 60 years of age, DNMT3A mutations predicted a worse OS (HR = 1.84;
      95% CI, 1.36-2.50; P<0.001). In addition, mutant DNMT3A predicted inferior OS (HR
      = 2.30; 95% CI, 1.78-2.97; P = 0.862) in patients with unfavorable genotype
      abnormalities. Similar results were also found in some other subgroups. However,
      no significant prognostic value was found on OS (HR = 1.40; 95% CI, 0.98-1.99; P
      = 0.798) in the favorable genotype subgroup. Similar results were found on RFS
      and EFS under different conditions. CONCLUSIONS: DNMT3A mutations have slightly
      but significantly poor prognostic impact on OS, RFS and EFS of adults with de
      novo AML in total population and some specific subgroups.

PMID- 24936646
TI  - Inflammatory biomarkers in atherosclerosis: pentraxin 3 can become a novel marker
      of plaque vulnerability.
AB  - Inflammation is crucially involved in the development of carotid plaques. We
      examined the relationship between plaque vulnerability and inflammatory
      biomarkers using intraoperative blood and tissue specimens. We examined 58
      patients with carotid stenosis. Following carotid plaque magnetic resonance
      imaging, 41 patients underwent carotid artery stenting (CAS) and 17 underwent
      carotid endarterectomy (CEA). Blood samples were obtained from the femoral artery
      (systemic) and common carotid artery immediately before and after CAS (local).
      Seventeen resected CEA tissue samples were embedded in paraffin, and
      histopathological and immunohistochemical analyses for IL-6, IL-10, E-selectin,
      adiponectin, and pentraxin 3 (PTX3) were performed. Serum levels of IL-6, IL
      1beta, IL-10, TNFalpha, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3 were
      measured by multiplex bead array system and ELISA. CAS-treated patients were
      classified as stable plaques (n = 21) and vulnerable plaques (n = 20). The
      vulnerable group showed upregulation of the proinflammatory cytokines (IL-6 and
      TNFalpha), endothelial activation markers (E-selectin and VCAM-1), and
      inflammation markers (hs-CRP and PTX3) and downregulation of the anti
      inflammatory markers (adiponectin and IL-10). PTX3 levels in both systemic and
      intracarotid samples before and after CAS were higher in the vulnerable group
      than in the stable group. Immunohistochemical analysis demonstrated that IL-6 was
      localized to inflammatory cells in the vulnerable plaques, and PTX3 was observed
      in the endothelial and perivascular cells. Our findings reveal that carotid
      plaque vulnerability is modulated by the upregulation and downregulation of
      proinflammatory and anti-inflammatory factors, respectively. PTX3 may thus be a
      potential predictive marker of plaque vulnerability. 

PMID- 24936648
TI  - Stressed yeast paint a picture of dorian gray.

PMID- 24936651
TI  - Nitrogen-doped carbon-wrapped porous single-crystalline CoO nanocubes for high
      performance lithium storage.
AB  - Herein, we have designed and synthesized a novel type of nitrogen-doped carbon
      supported CoO nanohybrids, i.e., nitrogen-doped carbon-wrapped porous single
      crystalline CoO nanocubes (CoO@N-C nanocubes), by using Co3O4 nanocubes as
      precursors. Owing to its unique structural features, the as-synthesized CoO@N-C
      nanocubes demonstrate markedly enhanced anodic performance in terms of reversible
      capacity, cycling stability, and rate capability, facilitating its application as
      a high-capacity, long-life, and high-rate anode for advanced lithium-ion
      batteries. 

PMID- 24936649
TI  - Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic parameters in
      patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and progressive
      vascular disorder characterized by increased pulmonary vascular resistance and
      right heart failure. The aim of this study was to analyze the Bone Morphogenetic
      Protein Receptor 2 (BMPR2), Activin A type II receptor like kinase 1
      (ALK1/ACVRL1) and potassium voltage-gated channel, shakerrelated subfamily,
      member 5 (KCNA5) genes in patients with idiopathic and associated PAH.
      Correlation among pathogenic mutations and clinical and functional parameters was
      further analyzed. METHODS AND RESULTS: Forty one patients and fifty controls were
      included in this study. Analysis of BMPR2, ACVRL1 and KCNA5 genes was performed
      by polymerase chain reaction (PCR) and direct sequencing. Fifty one nucleotide
      changes were detected in these genes in 40 of the 41 patients; only 22 of these
      changes, which were classified as pathogenic, have been detected in 21 patients
      (51.2%). Ten patients (62.5%) with idiopathic PAH and 10 (40%) with associated
      PAH showed pathogenic mutations in some of the three genes. Several clinical and
      hemodynamics parameters showed significant differences between carriers and non
      carriers of mutations, being more severe in carriers: mean pulmonary artery
      pressure (p = 0.043), pulmonary vascular resistence (p = 0.043), cardiac index (p
      = 0.04) and 6 minute walking test (p = 0.02). This differences remained unchanged
      after adjusting for PAH type (idiopathic vs non idiopathic). CONCLUSIONS:
      Pathogenic mutations in BMPR2 gene are frequent in patients with idiopathic and
      associated PAH group I. Mutations in ACVRL1 and KCNA5 are less frequent. The
      presence of these mutations seems to increase the severity of the disease.

PMID- 24936650
TI  - Association between tumor necrosis factor-alpha rs1800629 polymorphism and risk
      of asthma: a meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to explore the association between the
      TNF-alpha rs1800629 (also refers as -308G/A) polymorphism and asthma
      susceptibility. METHODS: We searched the Pubmed, Embase, Cochrane Central
      Register of Controlled Trials (CENTRAL) and Wanfang databases. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to calculate the strength of
      association. RESULTS: A total of 34 studies involving 5477 asthma patients and
      5962 controls were included in present study. The results indicated that TNF
      alpha rs1800629 polymorphism was significantly associated with asthma risk in a
      recessive genetic model (OR = 1.46, 95% CI 1.21-1.76, P<0.0001). Subgroup
      analyses found that the TNF-alpha rs1800629 polymorphism was significantly
      associated with asthma risk in West Asians and South Asians (OR = 2.47, 95% CI =
      1.48-4.12, P = 0.0005; OR = 1.83, 95% CI = 1.42-2.36, P<0.00001), but not East
      Asians and Caucasians. Furthermore, significant association also was observed in
      allergic asthma (OR = 1.51, 95% CI = 1.24-1.83, P<0.0001), adults and children
      (OR = 1.43, 95 CI%  = 1.07-1.91, P = 0.02; OR = 1.57, 95% CI = 1.19-2.06, P =
      0.001). CONCLUSIONS: This meta-analysis suggested that the rs1800629 polymorphism
      in TNF-alpha was a risk factor for asthma.

PMID- 24936652
TI  - Physiological and behavioural responses to noxious stimuli in the Atlantic cod
      (Gadus morhua).
AB  - In the present study, our aim was to compare physiological and behavioural
      responses to different noxious stimuli to those of a standardized innocuous
      stimulus, to possibly identify aversive responses indicative of injury detection
      in a commercially important marine teleost fish, the Atlantic cod. Individual
      fish were administered with a noxious stimulus to the lip under short-term
      general anaesthesia (MS-222). The noxious treatments included injection of 0.1%
      or 2% acetic acid, 0.005% or 0.1% capsaicin, or piercing the lip with a
      commercial fishing hook. Counts of opercular beat rate (OBR) at 10, 30, 60, 90
      and 120 min and observations of behaviour at 30 and 90 min post-treatment were
      compared with pre-treatment values and with control fish injected with
      physiological saline, an innocuous stimulus. Circulatory levels of physiological
      stress indicators were determined in all fish at 120 minutes post-treatment. All
      treatments evoked temporarily increased OBR that returned to pre-treatment levels
      at 60 minutes (saline, 0.005% capsaicin, hook), 90 minutes (0.1% acetic acid,
      0.1% capsaicin), or 120 minutes (2% acetic acid), but with no significant
      differences from the control group at any time point. Fish treated with 0.1% and
      2% acetic acid and 0.1% capsaicin displayed increased hovering close to the
      bottom of the aquaria and fish given 2% acetic acid and 0.1% capsaicin also
      displayed a reduced use of shelter. The only effect seen in hooked fish was brief
      episodes of lateral head shaking which were not seen pre-treatment or in the
      other groups, possibly reflecting a resiliency to tissue damage in the mouth area
      related to the tough nature of the Atlantic cod diet. There were no differences
      between groups in circulatory stress indicators two hours after treatment. This
      study provides novel data on behavioural indicators that could be used to assess
      potentially aversive events in Atlantic cod. 

PMID- 24936654
TI  - Effects of visual cortex activation on the nociceptive blink reflex in healthy
      subjects.
AB  - Bright light can cause excessive visual discomfort, referred to as photophobia.
      The precise mechanisms linking luminance to the trigeminal nociceptive system
      supposed to mediate this discomfort are not known. To address this issue in
      healthy human subjects we modulated differentially visual cortex activity by
      repetitive transcranial magnetic stimulation (rTMS) or flash light stimulation,
      and studied the effect on supraorbital pain thresholds and the nociceptive
      specific blink reflex (nBR). Low frequency rTMS that inhibits the underlying
      cortex, significantly decreased pain thresholds, increased the 1st nBR block ipsi
      and contralaterally and potentiated habituation contralaterally. After high
      frequency or sham rTMS over the visual cortex, and rMS over the right greater
      occipital nerve we found no significant change. By contrast, excitatory flash
      light stimulation increased pain thresholds, decreased the 1st nBR block of ipsi-
      and contralaterally and increased habituation contralaterally. Our data
      demonstrate in healthy subjects a functional relation between the visual cortex
      and the trigeminal nociceptive system, as assessed by the nociceptive blink
      reflex. The results argue in favour of a top-down inhibitory pathway from the
      visual areas to trigemino-cervical nociceptors. We postulate that in normal
      conditions this visuo-trigeminal inhibitory pathway may avoid disturbance of
      vision by too frequent blinking and that hypoactivity of the visual cortex for
      pathological reasons may promote headache and photophobia. 

PMID- 24936655
TI  - Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in
      Tripoli-Libya.
AB  - BACKGROUND: In 1998 Libya experienced a major outbreak of multiple blood borne
      viral hepatitis and HIV infections. Since then, no studies have been done on the
      epidemic features and risk factors of HBV, HCV, HIV and co-infection among the
      general population. METHODS: A prospective study was carried out using a multi
      centre clustering method to collect samples from the general population. The
      participants were interviewed, and relevant information was collected, including
      socio-demographic, ethnic, and geographic variables. This information was
      correlated with the risk factors involved in the transmission of HBV, HCV and
      HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV
      and anti-HIV using enzyme immunoassay. RESULTS: A total of 9,170 participants
      from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg
      was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence
      varied from one district to another. HBV was more prevalent among those aged over
      50 years and was associated with family history. Anti-HCV and anti-HIV were more
      prevalent among those aged 20-40 years. Intravenous drug use and blood
      transfusion were the main risk factors for HCV and HIV infection. CONCLUSION:
      HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence
      was associated with geographic, ethnic and socioeconomic variability within the
      community. HCV and HIV infections among the younger age groups are becoming an
      alarming issue. Regulations and health care education need to be implemented and
      longer term follow-up should be planned.

PMID- 24936656
TI  - Behavioural activation for depression; an update of meta-analysis of
      effectiveness and sub group analysis.
AB  - BACKGROUND: Depression is a common, disabling condition for which psychological
      treatments are recommended. Behavioural activation has attracted increased
      interest in recent years. It has been over 5 years since our meta-analyses
      summarised the evidence supporting and this systematic review updates those
      findings and examines moderators of treatment effect. METHOD: Randomised trials
      of behavioural activation for depression versus controls or anti-depressant
      medication were identified using electronic database searches, previous reviews
      and reference lists. Data on symptom level and study level moderators were
      extracted and analysed using meta-analysis, sub-group analysis and meta
      regression respectively. RESULTS: Twenty six randomised controlled trials
      including 1524 subjects were included in this meta-analysis. A random effects
      meta-analysis of symptom level post treatment showed behavioural activation to be
      superior to controls (SMD -0.74 CI -0.91 to -0.56, k = 25, N = 1088) and
      medication (SMD -0.42 CI -0.83 to-0.00, k = 4, N = 283). Study quality was low in
      the majority of studies and follow- up time periods short. There was no
      indication of publication bias and subgroup analysis showed limited association
      between moderators and effect size. CONCLUSIONS: The results in this meta
      analysis support and strengthen the evidence base indicating Behavioural
      Activation is an effective treatment for depression. Further high quality
      research with longer term follow-up is needed to strengthen the evidence base.

PMID- 24936657
TI  - Decreased expression of C10orf10 and its prognostic significance in human breast
      cancer.
AB  - Breast cancer is a common malignant tumor, which severely threatens the health of
      women with an increasing incidence in many countries. Here, we identified
      C10orf10 as a novel differentially expression gene using expression microarray
      screening. The expression analysis indicated that C10orf10 was frequently
      decreased in human breast cancers compared to noncancerous breast tissues (81/95,
      P = 0.0063). Kaplan-Meier analysis indicated that patients with low C10orf10
      expression showed a poorer prognosis both in mRNA (n = 1115, P = 0.0013) and
      protein (n = 100, P = 0.003) levels. Univariate and multivariate analysis showed
      that the C10orf10 expression was an independent prognostic factor for overall
      survival of breast cancer patients. Further analysis revealed that low expression
      of C10orf10 was an unfavorable factor for the prognosis of the patients who were
      luminal A, luminal B, Her2+ subtypes, at histological grade 2, lymph node
      negative and ER positive. Our data provided the first evidence that C10orf10
      expression was frequently decreased in breast cancer tissues, and low expression
      of C10orf10 may be an important prognostic factor for poorer survival time of
      breast cancer patients.

PMID- 24936659
TI  - Proteomic identification of pterostilbene-mediated anticancer activities in HepG2
      cells.
AB  - In the present study, we attempt to shed light on the underlying molecular
      mechanism of the anticancer activity of pterostilbene (PTS) in HepG2 cells
      through the proteomic approach. PTS was found to induce apoptosis by altering the
      expression of apoptotic genes and the G2/M phase of cell cycle arrest. Further,
      the 2-DE map showed the expression of 72 differentially regulated proteins in PTS
      treated HepG2 cells, of which 8 spots with >2 fold up- or down-regulated level
      were identified by MALDI-TOF analysis, which has a regulatory role in apoptosis.
      These findings for the first time offer valuable insights into the mechanism of
      apoptotis by PTS in HepG2 cells. 

PMID- 24936660
TI  - Prevalence, phenomenology and comorbidity of body dysmorphic disorder
      (dysmorphophobia) in a clinical population.
AB  - Dysmorphophobia (body dysmorphic disorder), defined as a preoccupation with an
      imaginary or minimal defect in appearance, has been known for more than a century
      but has received relatively little empirical study. The authors investigated the
      demographics, phenomenology, course, associated psychopathology and family
      history in a series of 58 patients (34 men and 24 women) with the disorder. The
      patients were assessed with the Hopkins Symptom Checklist and two specially
      constructed instruments developed by the authors. The mean age at onset of body
      dysmorphic disorder was 17 (sd = 3.8) years and the average duration was 9 (sd =
      5.3) years. The most common preoccupations were defects of the face, nose,
      genitals and legs. Seventy-nine percent of the patients reported excessive mirror
      checking and 53% reported attempts to camouflage their 'deformities'. As a result
      of their symptoms, 89.6% avoided the usual social activities, 51.7% showed an
      impairment of their academic or job performance, 45% experienced suicidal
      ideation and 36% showed aggressive behaviour. Seventy-two percent of the patients
      had an associated lifetime diagnosis of a major mood disorder and 74% of an
      anxiety disorder. Body dysmorphic disorder has a generally chronic course, causes
      considerable distress and a serious impairment in many areas, and shows strong
      links with mood and obsessive-compulsive disorders. 

PMID- 24936661
TI  - Depression in North India comparison of symptoms and life events with ocher
      patient groups.
AB  - Cross-cultural studies of depression have raised interesting issues in terms of
      symptoms and diagnosis in patients seeking treatment. To understand the symptom
      patterns of depression in a clinic population in north India, we studied 75
      consecutive patients diagnosed as suffering from depression. They were asked to
      describe their symptoms, life events in the year before the onset of depression,
      and family history. Sleep disturbances, low mood and irritability were common
      symptoms. Suicidal intent was reported by 54% of the sample, and guilt by 56%.
      Study of family history and life events suggests that in those with a negative
      family history, the onset of depression was more likely to be related to a
      significant life event the commonest being family conjunct. The symptoms of this
      patient group are compared with the symptoms of depression reported from clinical
      samples in south India, Bombay and the West. North Indian samples have low rates
      of delusions, whereas Bombay samples reveal low levels of hypochondriasis,
      agitation, guilt and suicidal thoughts. The roles of cultural factors, family
      responsibilities and expectations are discussed in relation to depression across
      cultures. These findings also have implications for the clinical management of
      patients from the North Indian diaspora presenting with depression. 

PMID- 24936658
TI  - The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable.
AB  - Nuclear receptors (NRs) are an important group of ligand-dependent
      transcriptional factors. Presently, no natural or synthetic ligand has been
      identified for a large group of orphan NRs. Small molecules to target these
      orphan NRs will provide unique resources for uncovering regulatory systems that
      impact human health and to modulate these pathways with drugs. The orphan NR
      tailless (TLX, NR2E1), a transcriptional repressor, is a major player in
      neurogenesis and Neural Stem Cell (NSC) derived brain tumors. No chemical probes
      that modulate TLX activity are available, and it is not clear whether TLX is
      druggable. To assess TLX ligand binding capacity, we created homology models of
      the TLX ligand binding domain (LBD). Results suggest that TLX belongs to an
      emerging class of NRs that lack LBD helices alpha1 and alpha2 and that it has
      potential to form a large open ligand binding pocket (LBP). Using a medium
      throughput screening strategy, we investigated direct binding of 20,000 compounds
      to purified human TLX protein and verified interactions with a secondary
      (orthogonal) assay. We then assessed effects of verified binders on TLX activity
      using luciferase assays. As a result, we report identification of three compounds
      (ccrp1, ccrp2 and ccrp3) that bind to recombinant TLX protein with affinities in
      the high nanomolar to low micromolar range and enhance TLX transcriptional
      repressive activity. We conclude that TLX is druggable and propose that our lead
      compounds could serve as scaffolds to derive more potent ligands. While our
      ligands potentiate TLX repressive activity, the question of whether it is
      possible to develop ligands to de-repress TLX activity remains open. 

PMID- 24936662
TI  - A comparison of patient-rated burden and incidence of side-effects: lithium
      versus valproate.
AB  - The purpose of the study was to determine if patients receiving valproate
      perceived a lesser burden than patients receiving lithium, and to determine the
      incidence of side-effects. Psychiatric inpatients with an affective component to
      their illness, receiving either lithium or valproate, were asked to complete
      several questionnaires, one of which was a newly developed visual-analogue scale
      to assess patient-rated level of burden. The scores were analyzed by Student's t
      test, and were also used to determine if any correlations existed. Twenty-nine
      patients were analyzed, and the patient-rated level of burden was found to be
      1.4+/- 1.3 for lithium and 1.2+/- 1.6 for valproate; (P=0.1, not significant).
      The mean numbers of side-effects reported were 12.3 +/- 6.7 for lithium and 18.7
      +/- 13.4 for valproate; (P=0.1). No correlation relationships were detected. We
      concluded that there was no difference in level of burden, and that burden scores
      could not be correlated with any variables. Similar studies should be conducted
      to assess patient preferences, with the hopes of increasing compliance and
      minimizing rehospitalizations. 

PMID- 24936663
TI  - Does case management influence the rate of violence and self-destructive
      behaviours in the severely mentally ill?
AB  - Case management is widely practised in the United States and Germany and has been
      adopted as the optimal model of community working in the United Kingdom.
      Randomized controlled trials suggest that case management is probably more
      effective than standard care at reducing rehospitalization and improving
      socialization and patients' satisfaction with services. Effects on
      symptomatology, quality of life and costs remain unclear. Surprisingly little
      research has focused on the effect of case management on reduction of violence
      and self-destructive behaviours. We examine the published studies in this area
      and suggest areas for further research. 

PMID- 24936664
TI  - Clinical applicability of therapeutic sleep deprivation.
AB  - The short-term antidepressive effect of single sleep deprivation (SD) treatment
      has been unanimously confirmed in a large number of studies. SD is most effective
      in patients with a major depressive episode (with melancholic features) but is
      also promising in other depressed patients suffering from vital symptoms and
      exhibiting a typical diurnal variation in mood (with morning low) irrespective of
      the type of depression. The SD modification of choice is partial SD in the second
      half of the night. SD is an easily applied treatment measure that is free from
      serious side effects. The tolerability can be improved further by performing SD
      in groups. SD is to be administered repeatedly rather than once and combined with
      pharmacotherapy. The mechanism of action underlying therapeutic SD has not yet
      been discovered. However, for its favorable influence on the overall
      antidepressive treatment outcome, SD should not only be applied in therapy
      resistant depression but is to be looked upon as part of the standard
      antidepressive somatotherapy. 

PMID- 24936665
TI  - Assessment and treatment of insomnia (including a case control study of patients
      with Primary Insomnia).
AB  - Insomnia is a subjective term describing the perception of disturbed or
      inadequate sleep. Causes include medical diseases, psychiatric disorders, drugs,
      behavioural factors, circadian dysrhythmias and primary sleep disorders. Insomnia
      is common, affecting approximately one-third of the total population, and of
      these about 10% consider it a chronic problem. Insomnia is more common in females
      and increases with age. Many people with insomnia resort to ineffective or
      dangerous self-treatment regimens and the combination of alcohol with non
      prescription drugs is common. We have carried out a study on 20 patients with
      Primary Insomnia and were able to demonstrate significant differences in both
      descriptive and objective EEG data between those with Primary Insomnia and
      controls. Careful evaluation of the sleep problem and accurate diagnosis are
      essential in order to choose the right treatment for an individual patient. When
      a specific problem is identified (psychiatric, physical, behavioural), then the
      underlying cause needs to be treated. Insomnia can be treated by either non
      pharmacological or pharmacological intervention, and often both are used
      simultaneously. It is recommended that hypnotic treatments should be used for no
      more than one month. 

PMID- 24936666
TI  - Neurosurgery for mental disorders (NMD) A clinical worldwide perspective: past,
      present and future.
AB  - The use of neurosurgery for mental disorders (NMD) is a clinical issue that
      involves many ethical considerations. It is a treatment that offers hope for many
      patients with severe and debilitating affective and anxiety disorders and should
      be widely available. Its current use worldwide (UK, Sweden, US, Australasia,
      Europe) is reviewed and the types of procedures currently used are explained
      (stereotactic subcaudate tractotomy, anterior capsulotomy, cingulotomy, limbic
      leucotomy). In addition, clinical strategies for the evaluation and management of
      patients both prior to and following NMD are discussed. 

PMID- 24936667
TI  - Recognition of depression and prevention of suicide: the role of general
      practitioners and general physicians.
AB  - Suicide is a major health problem throughout the world. After briefly describing
      the risk factors for suicide, the author focuses on depression, which is the
      major cause of suicide. Depression is a common illness, treatable not only in
      psychiatric settings, but also in primary care and general medicine.
      Consequently, physicians other than psychiatrists (primarily general
      practitioners) have an important role in suicide prevention. 

PMID- 24936668
TI  - A review of Huntington's disease.
AB  - Huntington's disease is an autosomal dominant neuropsychiatric disorder which
      usually afflicts people with dependents. Psychiatric disorders figure prominently
      in the differential diagnosis, and may complicate the clinical picture, sometimes
      even antedating the onset of neurological signs. Diagnosis is still usually
      clinical, for which some knowledge of the disease is required. Positron emission
      tomography, where available, can assist in early detection. Recent scientific
      breakthroughs have considerably improved the accuracy of predictive genetics, and
      the psychological outcome of such testing may be better than previously, but
      considerable ethical dilemmas have yet to be fully addressed. Genetic treatment
      is being considered. Drug treatments offer crude symptomatic improvement.
      Counselling and support services are essential, as are voluntary self-help
      organisations. Specific day and inpatient facilities are sparse. 

PMID- 24936671
TI  - Addendum.

PMID- 24936669
TI  - A patient who changed my practice: Benzodiazepines in schizophrenia?
AB  - The case of a 29-year-old man with catatonic symptoms is presented. After two
      attempts at treatment were unsuccessful, the symptoms faded with the use of the
      benxodiazepine lorazepam at an unusually high dose. 

PMID- 24936672
TI  - International calender.

PMID- 24936673
TI  - Vitamins C and E for asthma and exercise-induced bronchoconstriction.
AB  - BACKGROUND: The association between dietary antioxidants and asthma or exercise
      induced bronchoconstriction (EIB) is not fully understood. Vitamin C and vitamin
      E are natural antioxidants that are predominantly present in fruits and
      vegetables; inadequate vitamin E intake is associated with airway inflammation.
      It has been postulated that the combination may be more beneficial than either
      single antioxidant for people with asthma and exercise-induced
      bronchoconstriction. OBJECTIVES: To assess the effects of supplementation of
      vitamins C and E versus placebo (or no vitamin C and E supplementation) on
      exacerbations and health-related quality of life (HRQL) in adults and children
      with chronic asthma. To also examine the potential effects of vitamins C and E on
      exercise-induced bronchoconstriction in people with asthma and in people without
      a diagnosis of asthma who experience symptoms only on exercise. SEARCH METHODS:
      Trials were identified from the Cochrane Airways Review Group Specialised
      Register and from trial registry websites. Searches were conducted in September
      2013. SELECTION CRITERIA: We included randomised controlled trials of adults and
      children with a diagnosis of asthma. We separately considered trials in which
      participants had received a diagnosis of exercise-induced bronchoconstriction (or
      exercise-induced asthma). Trials comparing vitamin C and E supplementation versus
      placebo were included. We included trials in which asthma management for
      treatment and control groups included similar background therapy. Short-term use
      of vitamins C and E at the time of exacerbation or for cold symptoms in people
      with asthma is outside the scope of this review. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened the titles and abstracts of potential
      studies and subsequently screened full-text study reports for inclusion. We used
      standard methods as expected by The Cochrane Collaboration. MAIN RESULTS: It was
      not possible to aggregate the five included studies (214 participants). Four
      studies (206 participants) addressed the question of whether differences in
      outcomes were seen when vitamin C and E supplementation versus placebo was
      provided for participants with asthma, and only one of those studies (160
      children) included a paediatric population; the remaining three studies included
      a combined total of just 46 adults. An additional study considered the question
      of whether differences in outcomes were noted when vitamin C and E
      supplementation was compared with placebo for exercise-induced asthma; this trial
      included only eight participants. The randomisation process of the trials were
      unclear leading us to downgrade the quality of the evidence. Four of the studies
      were double blind while the other study was single blind.None of these studies
      provided data on our two prespecified primary outcome measures: exacerbations and
      HRQL. Lung function data obtained from the studies were inconclusive. The only
      studies that provided any suggestion of an effect, and only with some outcomes,
      were the paediatric study, especially for children with moderate to severe
      asthma, and the small study on exercise-induced asthma. Even so, this evidence
      was judged to be at moderate/low quality. Only one study contributed data on
      asthma symptoms and adverse events, reporting no evidence of an effect of the
      intervention for symptoms and that one participant in the treatment group dropped
      out due to cystitis. AUTHORS' CONCLUSIONS: It is not possible to draw firm
      conclusions from this review with respect to the comparison of vitamin C and E
      supplementation versus placebo in the management of asthma or exercise-induced
      bronchoconstriction. We found only one study relevant to exercise-induced
      bronchoconstriction; most included participants came from studies designed to
      assess the effect of vitamin supplementation on the impact of atmospheric
      pollutants (such as ozone). Evidence is lacking on the comparison of vitamin C
      and E supplementation versus placebo for asthma with respect to outcomes such as
      HRQL and exacerbations, which were not addressed by any of the included
      studies.When compared with lung function tests alone, HRQL scores and
      exacerbation frequency are better indicators of the severity of asthma, its
      impact on daily activities and its response to treatment in a patient population.
      These end points are well recognised in good quality studies of asthma
      management. However, clinical studies of vitamins C and E in the management of
      asthma using these important end points of exacerbations and effects on quality
      of life are not available, and evidence is insufficient to support robust
      conclusions on the role of vitamin C and E supplementation in asthma and exercise
      induced breathlessness.

PMID- 24936674
TI  - Acyloxylation of cyclic enones: synthesis of densely oxygenated guaianolides.
AB  - The alpha'-acyloxylation of cyclic enones with linear carboxylic acids is
      described. The reaction is promoted by KMnO4 in the presence of a carboxylic acid
      and its corresponding carboxylic anhydride. The optimization of the reaction has
      been carried out using the statistical methodology known as design of
      experiments. The optimized reaction conditions have been evaluated in terms of
      substrate scope and compatibility with different functional groups. The
      methodology has been applied to the synthesis of densely oxygenated guaianes and
      guaianolides. 

PMID- 24936675
TI  - Predicting future longevity: at long last, extrapolation is on the way out.

PMID- 24936676
TI  - Immunohistochemical expression of MCM2 in nonmelanoma epithelial skin cancers.
AB  - Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent
      45.5% and 37.02%, respectively, of total malignant skin cancer according to the
      latest registry of Egyptian National Cancer Institute. Minichromosome maintenance
      (MCM) proteins are essential replication initiation factors. The current study
      examined the immunohistochemical expression of MCM2 in normal skin (10 cases),
      some proliferative skin lesions (6 psoriasis, 2 keratoacanthoma, and 2 seborrheic
      keratosis), and nonmelanoma epithelial skin cancers (20 BCC and 21 SCC). MCM2 was
      expressed in basal layer of normal epidermis and upregulated in proliferative
      skin lesions and nonmelanoma epithelial skin cancers without significant
      differences between the latter groups (P > 0.05). Mean and median values of MCM2
      percentage of expression in BCC were higher than that of SCC (P = 0.004). MCM2
      promotes proliferative capacity of the cells manifested by its expression in
      basal layer of epidermis, hyperproliferative skin lesions, and malignant
      cutaneous tumors. Proliferative capacity of BCC may be higher than SCC and this
      does not necessarily reflect aggressive behavior.

PMID- 24936677
TI  - Eye movements disrupt episodic future thinking.
AB  - Remembering the past and imagining the future both rely on complex mental
      imagery. We considered the possibility that constructing a future scene might tap
      a component of mental imagery that is not as critical for remembering past
      scenes. Whereas visual imagery plays an important role in remembering the past,
      we predicted that spatial imagery plays a crucial role in imagining the future.
      For the purpose of teasing apart the different components underpinning scene
      construction in the two experiences of recalling episodic memories and shaping
      novel future events, we used a paradigm that might selectively affect one of
      these components (i.e., the spatial). Participants performed concurrent eye
      movements while remembering the past and imagining the future. These concurrent
      eye movements selectively interfere with spatial imagery, while sparing visual
      imagery. Eye movements prevented participants from imagining complex and detailed
      future scenes, but had no comparable effect on the recollection of past scenes.
      Similarities between remembering the past and imagining the future are coupled
      with some differences. The present findings uncover another fundamental
      divergence between the two processes. 

PMID- 24936678
TI  - Radioiodinated benzyloxybenzene derivatives: a class of flexible ligands target
      to beta-amyloid plaques in Alzheimer's brains.
AB  - Benzyloxybenzene, as a novel flexible scaffold without rigid planarity, was
      synthesized and evaluated as ligand toward Abeta plaques. The binding site
      calculated for these flexible ligands was the hydrophobic Val18_Phe20 channel on
      the flat surface of Abeta fiber. Structure-activity relationship analysis
      generated a common trend that binding affinities declined significantly from para
      substituted ligands to ortho-substituted ones, which was also quantitatively
      illustrated by 3D-QSAR modeling. Autoradiography in vitro further confirmed the
      high affinities of radioiodinated ligands [125I]4, [125I]24, and [125I]22
      (Ki=24.3, 49.4, and 17.6 nM, respectively). In biodistribution, [125I]4 exhibited
      high initial uptake and rapid washout property in the brain with brain2
      min/brain60 min ratio of 16.3. The excellent in vitro and in vivo biostability of
      [125I]4 enhanced its potential for clinical application in SPECT imaging of Abeta
      plaques. This approach could also allow the design of a new generation of Abeta
      targeting ligands without rigid and planar framework.

PMID- 24936681
TI  - Beyond fractional anisotropy: extraction of bundle-specific structural metrics
      from crossing fiber models.
AB  - Diffusion MRI (dMRI) measurements are used for inferring the microstructural
      properties of white matter and to reconstruct fiber pathways. Very often voxels
      contain complex fiber configurations comprising multiple bundles, rendering the
      simple diffusion tensor model unsuitable. Multi-compartment models deliver a
      convenient parameterization of the underlying complex fiber architecture, but
      pose challenges for fitting and model selection. Spherical deconvolution, in
      contrast, very economically produces a fiber orientation density function (fODF)
      without any explicit model assumptions. Since, however, the fODF is represented
      by spherical harmonics, a direct interpretation of the model parameters is
      impossible. Based on the fact that the fODF can often be interpreted as
      superposition of multiple peaks, each associated to one relatively coherent fiber
      population (bundle), we offer a solution that seeks to combine the advantages of
      both approaches: first the fiber configuration is modeled as fODF represented by
      spherical harmonics and then each of the peaks is parameterized separately in
      order to characterize the underlying bundle. In this work, the fODF peaks are
      approximated by Bingham distributions, capturing first and second-order
      statistics of the fiber orientations, from which we derive metrics for the
      parametric quantification of fiber bundles. We propose meaningful relationships
      between these measures and the underlying microstructural properties. We focus on
      metrics derived directly from properties of the Bingham distribution, such as
      peak length, peak direction, peak spread, integral over the peak, as well as a
      metric derived from the comparison of the largest peaks, which probes the
      complexity of the underlying microstructure. We compare these metrics to the
      conventionally used fractional anisotropy (FA) and show how they may help to
      increase the specificity of the characterization of microstructural properties.
      While metrics relying on the first moments of the Bingham distributions provide
      relatively robust results, second-order metrics representing the peak spread are
      only meaningful, if the SNR is very high and no fiber crossings are present in
      the voxel. 

PMID- 24936679
TI  - Total and free thyroxine and triiodothyronine: measurement discrepancies,
      particularly in inpatients.
AB  - OBJECTIVE: We compared the performance of tandem mass spectrometry versus
      immunoassay for measuring thyroid hormones in a diverse group of inpatients and
      outpatients. METHODS: Thyroxine (T4), triiodothyronine (T3), free thyroxine
      (FT4), and free triiodothyronine (FT3) were measured by liquid chromatography
      tandem mass spectrometry and immunoassay in 100 patients and the two assays were
      compared. RESULTS: T4 and T3 values measured by the two different assays
      correlated well with each other (r=0.91-0.95). However, the correlation was less
      good at the extremes (r=0.51-0.75). FT4 and FT3 concentrations measured by the
      two assays correlated less well with each other (r=0.75 and 0.50 respectively).
      The studied analytes had poor inverse correlation with the log-transformed TSH
      values (r=-0.22-0.51) in the population as a whole. The strongest correlations
      were seen in the groups of outpatients (r=-0.25-0.61). The weakest degree of
      correlation was noted in the inpatient group, with many correlations actually
      being positive. CONCLUSION: The worst between-assay correlation was demonstrated
      at low and high hormone concentrations, in the very concentration ranges where
      accurate assay performance is typically most clinically important. Based on the
      lesser susceptibility of mass spectrometry to interferences from conditions such
      as binding protein abnormalities, we speculate that mass spectrometry better
      reflects the clinical situation. In this mixed population of inpatients and
      outpatients, we also note failure of assays to conform to the anticipated inverse
      linear relationship between thyroid hormones and log-transformed TSH.

PMID- 24936680
TI  - Sleep sharpens sensory stimulus coding in human visual cortex after fear
      conditioning.
AB  - Efficient perceptual identification of emotionally-relevant stimuli requires
      optimized neural coding. Because sleep contributes to neural plasticity
      mechanisms, we asked whether the perceptual representation of emotionally
      relevant stimuli within sensory cortices is modified after a period of sleep. We
      show combined effects of sleep and aversive conditioning on subsequent
      discrimination of face identity information, with parallel plasticity in the
      amygdala and visual cortex. After one night of sleep (but neither immediately nor
      after an equal waking interval), a fear-conditioned face was better detected when
      morphed with another identity. This behavioral change was accompanied by
      increased selectivity of the amygdala and face-responsive fusiform regions.
      Overnight neural changes can thus sharpen the representation of threat-related
      stimuli in cortical sensory areas, in order to improve detection in impoverished
      or ambiguous situations. These findings reveal an important role of sleep in
      shaping cortical selectivity to emotionally-relevant cues and thus promoting
      adaptive responses to new dangers. 

PMID- 24936682
TI  - Interoperable atlases of the human brain.
AB  - The last two decades have seen an unprecedented development of human brain
      mapping approaches at various spatial and temporal scales. Together, these have
      provided a large fundus of information on many different aspects of the human
      brain including micro- and macrostructural segregation, regional specialization
      of function, connectivity, and temporal dynamics. Atlases are central in order to
      integrate such diverse information in a topographically meaningful way. It is
      noteworthy, that the brain mapping field has been developed along several major
      lines such as structure vs. function, postmortem vs. in vivo, individual features
      of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to
      understand human brain organization, however, it seems inevitable that these
      different lines are integrated and combined into a multimodal human brain model.
      To this aim, we held a workshop to determine the constraints of a multi-modal
      human brain model that are needed to enable (i) an integration of different
      spatial and temporal scales and data modalities into a common reference system,
      and (ii) efficient data exchange and analysis. As detailed in this report, to
      arrive at fully interoperable atlases of the human brain will still require much
      work at the frontiers of data acquisition, analysis, and representation. Among
      them, the latter may provide the most challenging task, in particular when it
      comes to representing features of vastly different scales of space, time and
      abstraction. The potential benefits of such endeavor, however, clearly outweigh
      the problems, as only such kind of multi-modal human brain atlas may provide a
      starting point from which the complex relationships between structure, function,
      and connectivity may be explored. 

PMID- 24936683
TI  - Dynamic functional imaging of brain glucose utilization using fPET-FDG.
AB  - Glucose is the principal source of energy for the brain and yet the dynamic
      response of glucose utilization to changes in brain activity is still not fully
      understood. Positron emission tomography (PET) allows quantitative measurement of
      glucose metabolism using 2-[(18)F]-fluorodeoxyglucose (FDG). However, FDG PET in
      its current form provides an integral (or average) of glucose consumption over
      tens of minutes and lacks the temporal information to capture physiological
      alterations associated with changes in brain activity induced by tasks or drug
      challenges. Traditionally, changes in glucose utilization are inferred by
      comparing two separate scans, which significantly limits the utility of the
      method. We report a novel method to track changes in FDG metabolism dynamically,
      with higher temporal resolution than exists to date and within a single session.
      Using a constant infusion of FDG, we demonstrate that our technique (termed fPET
      FDG) can be used in an analysis pipeline similar to fMRI to define within-session
      differential metabolic responses. We use visual stimulation to demonstrate the
      feasibility of this method. This new method has a great potential to be used in
      research protocols and clinical settings since fPET-FDG imaging can be performed
      with most PET scanners and data acquisition and analysis are straightforward.
      fPET-FDG is a highly complementary technique to MRI and provides a rich new way
      to observe functional changes in brain metabolism. 

PMID- 24936684
TI  - COMT Val158Met genotype is associated with fluctuations in working memory
      performance: converging evidence from behavioural and single-trial P3b measures.
AB  - Intra-subject variability in reaction times (ISV) is a promising endophenotype
      for several psychiatric conditions, but its neural underpinnings are not yet
      established. Converging evidence from neuroimaging, molecular genetics, and
      psychopharmacology suggests that ISV could index catecholaminergically-mediated
      neural noise. The fine-grained temporal resolution of electroencephalography is
      ideal for investigating ISV, but only if potential neural correlates of ISV can
      be assessed in single trials. Based on evidence that ISV is associated with
      dopaminergic functioning, we apply a recently developed method of single-trial
      P3b analysis to investigate the association of COMT Val(158)Met genotype with
      measures of ISV on the behavioural and neural levels at different working memory
      loads. Greater number of Met alleles was associated with poorer and more intra
      individually variable performance on the tasks, and greater latency jitter in
      single-trial P3bs. These converging results at the behavioural and
      neurophysiological levels confirm previous observations that prefrontal dopamine
      availability is associated with stability and accuracy of cognitive performance.
      Together with previous studies, these data imply pleiotropic cognitive effects of
      COMT genotype. 

PMID- 24936686
TI  - Intracerebral electrical stimulation of a face-selective area in the right
      inferior occipital cortex impairs individual face discrimination.
AB  - During intracerebral stimulation of the right inferior occipital cortex, a
      patient with refractory epilepsy was transiently impaired at discriminating two
      simultaneously presented photographs of unfamiliar faces. The critical electrode
      contact was located in the most posterior face-selective brain area of the human
      brain (right "occipital face area", rOFA) as shown both by low- (ERP) and high
      frequency (gamma) electrophysiological responses as well as a face localizer in
      fMRI. At this electrode contact, periodic visual presentation of 6 different
      faces by second evoked a larger electrophysiological periodic response at 6 Hz
      than when the same face identity was repeated at the same rate. This
      intracerebral EEG repetition suppression effect was markedly reduced when face
      stimuli were presented upside-down, a manipulation that impairs individual face
      discrimination. These findings provide original evidence for a causal
      relationship between the face-selective right inferior occipital cortex and
      individual face discrimination, independently of long-term memory
      representations. More generally, they support the functional value of
      electrophysiological repetition suppression effects, indicating that these
      effects can be used as an index of a necessary neural representation of the
      changing stimulus property.

PMID- 24936685
TI  - Axonal transport rate decreased at the onset of optic neuritis in EAE mice.
AB  - Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an
      inflammatory demyelinating neurodegenerative disease. Impaired axonal transport
      has been considered as an early event of neurodegenerative diseases. However, few
      studies have assessed the integrity of axonal transport in MS or its animal
      models. We hypothesize that axonal transport impairment occurs at the onset of
      optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this
      study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in
      optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was
      assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by
      measuring the rate of increased total optic nerve signal enhancement, and (b)
      Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve
      length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+)
      accumulation rate was significantly decreased by 19% and 38% for EAE mice with
      moderate and severe optic neuritis, respectively. The axonal transport rate of
      Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and
      severe optic neuritis, respectively. The degree of axonal transport deficit
      correlated with the extent of impaired visual function and diminished microtubule
      associated tubulins, as well as the severity of inflammation, demyelination, and
      axonal injury at the onset of optic neuritis. 

PMID- 24936687
TI  - Synchronous brain activity across individuals underlies shared psychological
      perspectives.
AB  - For successful communication, we need to understand the external world
      consistently with others. This task requires sufficiently similar cognitive
      schemas or psychological perspectives that act as filters to guide the selection,
      interpretation and storage of sensory information, perceptual objects and events.
      Here we show that when individuals adopt a similar psychological perspective
      during natural viewing, their brain activity becomes synchronized in specific
      brain regions. We measured brain activity with functional magnetic resonance
      imaging (fMRI) from 33 healthy participants who viewed a 10-min movie twice,
      assuming once a 'social' (detective) and once a 'non-social' (interior decorator)
      perspective to the movie events. Pearson's correlation coefficient was used to
      derive multisubject voxelwise similarity measures (inter-subject correlations;
      ISCs) of functional MRI data. We used k-nearest-neighbor and support vector
      machine classifiers as well as a Mantel test on the ISC matrices to reveal brain
      areas wherein ISC predicted the participants' current perspective. ISC was
      stronger in several brain regions--most robustly in the parahippocampal gyrus,
      posterior parietal cortex and lateral occipital cortex--when the participants
      viewed the movie with similar rather than different perspectives. Synchronization
      was not explained by differences in visual sampling of the movies, as estimated
      by eye gaze. We propose that synchronous brain activity across individuals
      adopting similar psychological perspectives could be an important neural
      mechanism supporting shared understanding of the environment.

PMID- 24936688
TI  - Ventral medial prefrontal cortex and person evaluation: forming impressions of
      others varying in financial and moral status.
AB  - The current study investigated ventromedial prefrontal cortex (VMPFC) activity
      during impression formation of individuals varying on distinct dimensions of
      social status. In a block-design functional magnetic resonance imaging (fMRI)
      experiment, participants were presented with photographs of faces paired with a
      colored background indicating their lower, same, or higher financial status, or
      lower, same, or higher moral status. Participants were asked to form an
      impression of the targets, but were not instructed to explicitly evaluate them
      based on social status. Building on previous findings (Cloutier, Ambady, Meagher,
      & Gabrieli, 2012), a region of interest analysis revealed the interaction of
      status dimension and level in VMPFC, finding not only preferential response to
      targets with higher compared to lower moral status as previously demonstrated,
      but also greater response to targets with lower compared to higher financial
      status. The implications of these results are discussed with an emphasis towards
      better understanding the impact of social status on social cognition and
      uncovering the neural substrates of person evaluation. 

PMID- 24936689
TI  - [Incidental maxillary sinus finding in a 16-year-old patient].

PMID- 24936690
TI  - [Complications in children and adults with cochlear implant].
AB  - BACKGROUND: Complications in Children and Adults with Cochlear Implant
      Background: Cochlear Implants (CI) are developed in the last 20 years to a
      regular therapy in congenital deaf children/newborns and deafened teens and
      adults. The success of speech understanding with the CI in adults is so
      extraordinary that meanwhile also unilateral deaf, contralateral normal hearing
      persons are implanted. In case of early implanted children a nearly normal speech
      development is possible in most of the cases. MATERIAL UND METHODS: Nevertheless
      the surgical procedures is a challenge concerning the potential complications
      combined with a foreign body, the CI, in a non-steril part of the ear. RESULTS:
      This paper reports on the complications in a patients collective, implanted
      within 21 years. Separated within the severity of the complications and their
      therapeutic consequences (conservative and surgical) it could be shown that the
      incidence of severe perioperative complications within the second decade could be
      reduced from 3.92% (first decade) to 1.8%. Also the companies have learned to
      construct the products more save. CONCLUSION: In summary the reliable and
      complete postoperative control and the modification of therapy concepts leads to
      a constant reduction of complications.

PMID- 24936691
TI  - Evaluation of rigid bronchoscopy-guided percutaneous dilational tracheostomy. A
      pilot study.
AB  - RATIONALE: Rigid bronchoscopy-guided (RBG) percutaneous tracheostomy has been
      used in patients with morbid obesity, prior neck surgery, distorted airway
      anatomy, and uncorrected coagulopathy where standard percutaneous dilational
      tracheostomy (PDT) is relatively contraindicated. OBJECTIVES: This study aims to
      describe a standardized approach to incorporate RBG-PDT in clinical practice.
      METHODS AND MEASUREMENTS: Retrospective case series of patients who underwent RBG
      PDT from 2008 to 2012 at Beth Israel Deaconess Medical Center. Patient medical
      records were reviewed for demographics, comorbid conditions, American Society of
      Anesthesiologists classification, indication for tracheostomy, duration of
      procedure, and periprocedural complications. MAIN RESULTS: A total of 35 patients
      underwent RBG-PDT, including 24 men, with a mean age of 66 years (+/-11 yr;
      range, 42-88 yr). The mean body mass index was 34 kg/m(2). The mean procedure
      time was 32 (+/-10) minutes, with a median of 33 minutes. The most common
      indication for tracheostomy was failure to wean from mechanical ventilation,
      followed by tracheal stenosis and tracheobronchomalacia. The most common
      indications for RBG-PDT were complex airway, obesity, and coagulopathy. There
      were no periprocedural complications of consequence, or mortality associated with
      the procedure. CONCLUSIONS: RBG-PDT is safe and effective in a population of high
      risk patients who are otherwise not considered good candidates for standard PDT.

PMID- 24936692
TI  - Only time will tell. Data-driven approaches to phenotyping critical illness.

PMID- 24936693
TI  - Reducing the risk of rehospitalization in patients with chronic obstructive
      pulmonary disease exacerbations. Fewer known unknowns.

PMID- 24936694
TI  - Extracorporeal life support. A "breath-taking" technology?

PMID- 24936695
TI  - My Journey through idiopathic pulmonary fibrosis.

PMID- 24936696
TI  - Hypoxemia in a patient with pulmonary arterial hypertension: getting to the heart
      of the matter.

PMID- 24936697
TI  - No gravity in this cavity.

PMID- 24936698
TI  - Don't waste your breath.

PMID- 24936699
TI  - Severe sleep-disordered breathing in an adult with fusion of cervical spine.

PMID- 24936700
TI  - Why do some of us still hyper-sedate mechanically ventilated patients?

PMID- 24936701
TI  - Reply: why do some of us still hyper-sedate mechanically ventilated patients?

PMID- 24936702
TI  - Diffuse alveolar hemorrhage induced by sevoflurane.

PMID- 24936703
TI  - Guillain-Barre syndrome related to pulmonary tuberculosis.

PMID- 24936705
TI  - Reversible photoswitching of triplet-triplet annihilation upconversion using
      dithienylethene photochromic switches.
AB  - Reversible photoswitched triplet-triplet annihilation upconversion (TTA UC) was
      demonstrated with dithienylethene (DTE) derivatives as the photochromic units,
      2,6-diiodoBodipy as the triplet photosensitizer, and perylene as the triplet
      acceptor/emitter. The TTA UC is undisturbed by the open-form DTE but can be
      switched OFF upon photoirradiation of the mixture of the three components at 254
      nm, i.e., by the closed-form DTE. Subsequent visible light irradiation restores
      the TTA UC. By studying the competitive triplet-state energy-transfer processes
      with nanosecond time-resolved transient difference absorption and fluorescence
      spectroscopy, we confirmed that the quenching of the perylene triplet excited
      state by closed-form DTE is dominant among the four possible quenching processes.

PMID- 24936704
TI  - Seamless metallic coating and surface adhesion of self-assembled bioinspired
      nanostructures based on di-(3,4-dihydroxy-L-phenylalanine) peptide motif.
AB  - The noncoded aromatic 3,4-dihydroxy-L-phenylalanine (DOPA) amino acid has a
      pivotal role in the remarkable adhesive properties displayed by marine mussels.
      These properties have inspired the design of adhesive chemical entities through
      various synthetic approaches. DOPA-containing bioinspired polymers have a broad
      functional appeal beyond adhesion due to the diverse chemical interactions
      presented by the catechol moieties. Here, we harnessed the molecular self
      assembly abilities of very short peptide motifs to develop analogous DOPA
      containing supramolecular polymers. The DOPA-containing DOPA-DOPA and Fmoc-DOPA
      DOPA building blocks were designed by substituting the phenylalanines in the well
      studied diphenylalanine self-assembling motif and its 9-fluorenylmethoxycarbonyl
      (Fmoc)-protected derivative. These peptides self-organized into fibrillar
      nanoassemblies, displaying high density of catechol functional groups.
      Furthermore, the Fmoc-DOPA-DOPA peptide was found to act as a low molecular
      weight hydrogelator, forming self-supporting hydrogel which was rheologically
      characterized. We studied these assemblies using electron microscopy and explored
      their applicative potential by examining their ability to spontaneously reduce
      metal cations into elementary metal. By applying ionic silver to the hydrogel, we
      observed efficient reduction into silver nanoparticles and the remarkable
      seamless metallic coating of the assemblies. Similar redox abilities were
      observed with the DOPA-DOPA assemblies. In an effort to impart adhesiveness to
      the obtained assemblies, we incorporated lysine (Lys) into the Fmoc-DOPA-DOPA
      building block. The assemblies of Fmoc-DOPA-DOPA-Lys were capable of gluing
      together glass surfaces, and their adhesion properties were investigated using
      atomic force microscopy. Taken together, a class of DOPA-containing self
      assembling peptides was designed. These nanoassemblies display unique properties
      and can serve as multifunctional platforms for various biotechnological
      applications.

PMID- 24936706
TI  - Reduction of the nitro group to amine by hydroiodic acid to synthesize o
      aminophenol derivatives as putative degradative markers of neuromelanin.
AB  - Neuromelanin (NM) is produced in dopaminergic neurons of the substantia nigra
      (SN) and in noradrenergic neurons of the locus coeruleus (LC). The synthesis of
      NM in those neurons is a component of brain aging and there is the evidence that
      this pigment can be involved in the pathogenesis of neurodegenerative diseases
      such as Parkinson's disease. NM is believed to derive from the oxidative
      polymerization of dopamine (DA) or norepinephrine (NE) with the participation of
      cysteine, dolichols and proteins. However, there are still unknown aspects in the
      chemical structure of NM from SN (SN-NM) and LC (LC-NM). In this study, we
      designed a new method to synthesize o-aminophenol compounds as putative
      degradation products of catecholamines and their metabolites which may be
      incorporated into NM. Those compounds are aminohydroxyphenylethylamine (AHPEA)
      isomers, aminohydroxyphenylacetic acid (AHPAA) isomers and
      aminohydroxyethylbenzene (AHEB) isomers, which are expected to arise from DA or
      NE, 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylmandelic acid
      (DOMA) and 3,4-dihydroxyphenylethanol (DOPE) or 3,4-dihydroxyphenylethyleneglycol
      (DOPEG), respectively. These o-aminophenol compounds were synthesized by the
      nitration of phenol derivatives followed by reduction with hydroiodic acid (HI),
      and they could be identified by HPLC in HI hydrolysates of SN-NM and LC-NM. This
      degradative approach by HI hydrolysis allows the identification of catecholic
      precursors unique to SN-NM and LC-NM, which are present in catecholaminergic
      neurons. 

PMID- 24936707
TI  - A class of promising acaricidal tetrahydroisoquinoline derivatives: synthesis,
      biological evaluation and structure-activity relationships.
AB  - As part of our continuing research on isoquinoline acaricidal drugs, this paper
      reports the preparation of a series of the 2-aryl-1-cyano-1,2,3,4
      tetrahydroisoquinolines with various substituents on the N-phenyl ring, their in
      vitro acaricidal activities against Psoroptes cuniculi, a mange mite, and
      discusses their SAR as well. The structures of all compounds, including 12 new
      ones, were elucidated by analysis of UV, IR, NMR, ESI-MS, HR-MS spectra and X-ray
      diffraction experiments. All target compounds showed varying degrees of activity
      at 0.4 mg/mL. Compound 1 showed the strongest activity, with a 50% lethal
      concentration value (LC50) of 0.2421 MUg/mL and 50% lethal time value (LT50) of
      7.79 h, comparable to the standard drug ivermectin (LC50 = 0.2474 MUg/mL; LT50 =
      20.9 h). The SAR showed that the substitution pattern on the N-aromatic ring
      exerted a significant effect on the activity. The substituents 2'-F, 3'-F, 2'-Cl,
      2'-Br and 2'-CF3 remarkably enhanced the activity. Generally, for the isomers
      with the same substituents at different positions, the order of the activity was
      ortho > meta > para. It was concluded that the target compounds represent a class
      of novel promising candidates or lead compounds for the development of new
      tetrahydroisoquinoline acaricidal agents. 

PMID- 24936708
TI  - Bioresolution production of (2R,3S)-ethyl-3-phenylglycidate for chemoenzymatic
      synthesis of the taxol C-13 side chain by Galactomyces geotrichum ZJUTZQ200, a
      new epoxide-hydrolase-producing strain.
AB  - A newly isolated Galactomyces geotrichum ZJUTZQ200 strain containing an epoxide
      hydrolase was used to resolve racemic ethyl 3-phenylglycidate (rac-EPG) for
      producing (2R,3S)-ethyl-3-phenylglycidate ((2R,3S)-EPG). G. geotrichum ZJUTZQ200
      was verified to be able to afford high enantioselectivity in whole cell catalyzed
      synthesis of this chiral phenylglycidate synthon. After the optimization of the
      enzymatic production and bioresolution conditions, (2R,3S)-EPG was afforded with
      high enantioselectivity (e.e.S > 99%, E > 49) after a 8 h reaction. The co
      solvents, pH buffer solutions and substrate/cell ratio were found to have
      significant influences on the bioresolution properties of G. geotrichum
      ZJUTZQ200. Based on the bioresolution product (2R,3S)-EPG, taxol's side chain
      ethyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropionate was successfully
      synthesized by a chemoenzymatic route with high enantioselectivity (e.e.S > 95%).

PMID- 24936709
TI  - RutheniumII(eta6-arene) complexes of thiourea derivatives: synthesis,
      characterization and urease inhibition.
AB  - RuII(arene) complexes have emerged as a versatile class of compounds to design
      metallodrugs as potential treatment for a wide range of diseases including cancer
      and malaria. They feature modes of action that involve classic DNA binding like
      platinum anticancer drugs, may covalent binding to proteins, or multimodal
      biological activity. Herein, we report the synthesis and urease inhibition
      activity of RuII(arene) complexes of the general formula [RuII(eta6-p
      cymene)(L)Cl2] and [RuII(eta6-p-cymene)(PPh3)(L)Cl]PF6 with S-donor systems (L)
      based on heterocyclic thiourea derivatives. The compounds were characterized by
      1H-, 13C{1H}- and 31P{1H}-NMR spectroscopy, as well as elemental analysis. The
      crystal structure of [chlorido(eta6-p-cymene)(imidazolidine-2
      thione)(triphenylphosphine)ruthenium(II)] hexafluorophosphate 11 was determined
      by X-ray diffraction analysis. A signal in the range 175-183 ppm in the 13C{1H}
      NMR spectrum indicates the presence of a thione rather than a thiolate. This
      observation was also confirmed in the solid state by X-ray diffraction analysis
      of 11 which shows a C=S bond length of 1.720 A. The compounds were tested for
      urease inhibitory activity and the thiourea-derived ligands exhibited moderate
      activity, whereas their corresponding Ru(arene) complexes were not active. 

PMID- 24936710
TI  - Effect of two anti-fungal treatments (metrafenone and boscalid plus kresoxim
      methyl) applied to vines on the color and phenol profile of different red wines.
AB  - The effect of two anti-fungal treatments (metrafenone and boscalid + kresoxim
      methyl) on the color and phenolic profile of Tempranillo and Graciano red wines
      has been studied. To evaluate possible modifications in color and phenolic
      composition of wines, control and wines elaborated with treated grapes under good
      agricultural practices were analyzed. Color was assessed by Glories and CIELab
      parameters. Color changes were observed for treated wines with boscalid +
      kresoxim-methyl, leading to the production of wines with less color vividness.
      Phenolic profile was characterized by HPLC analysis. Boscalid + kresoxim-methyl
      treatment promoted the greatest decrease on the phenolic content in wines. 

PMID- 24936711
TI  - Article expression, purification, and characterization of Cu/ZnSOD from Panax
      ginseng.
AB  - Superoxide dismutase (SOD) has a strong antioxidant effect, but the traditional
      SOD extraction method is not the most efficient method of SOD amplification. In
      this study, we report the cloning of the Cu/ZnSOD gene from Panax ginseng into a
      temperature-regulated expression plasmid, pBV220. Cu/ZnSOD inclusion bodies were
      expressed in E. coli at a high level. Then, the inclusion bodies were purified by
      ion-exchange chromatography and molecular sieve chromatography. Finally, we
      obtained stable SOD in the bacterial broth, with a protein content of 965 mg/L
      and enzyme specific activity of 9389.96 U/mg. These results provide a foundation
      for future studies on the antioxidant mechanisms of ginseng and the development
      and application of ginseng Cu/ZnSOD. 

PMID- 24936713
TI  - Cardiac risk factors: foreword.

PMID- 24936712
TI  - Encapsulation kinetics and dynamics of carbon monoxide in clathrate hydrate.
AB  - Carbon monoxide clathrate hydrate is a potentially important constituent in the
      solar system. In contrast to the well-established relation between the size of
      gaseous molecule and hydrate structure, previous work showed that carbon monoxide
      molecules preferentially form structure-I rather than structure-II gas hydrate.
      Resolving this discrepancy is fundamentally important to understanding clathrate
      formation, structure stabilization and the role the dipole moment/molecular
      polarizability plays in these processes. Here we report the synthesis of
      structure-II carbon monoxide hydrate under moderate high-pressure/low-temperature
      conditions. We demonstrate that the relative stability between structure-I and
      structure-II hydrates is primarily determined by kinetically controlled cage
      filling and associated binding energies. Within hexakaidecahedral cage, molecular
      dynamic simulations of density distributions reveal eight low-energy wells
      forming a cubic geometry in favour of the occupancy of carbon monoxide molecules,
      suggesting that the carbon monoxide-water and carbon monoxide-carbon monoxide
      interactions with adjacent cages provide a significant source of stability for
      the structure-II clathrate framework. 

PMID- 24936714
TI  - Cardiac risk factors: biomarkers and genetic tests to determine cardiovascular
      risk.
AB  - Current guidelines recommend global risk assessment instruments as the primary
      approach for determining risk of coronary heart disease (CHD). The Framingham
      Risk Score (FRS) yields a 10-year risk of CHD, whereas the newer Pooled Cohort
      Equations yield a 10-year risk of stroke or CHD. High-sensitivity C-reactive
      protein, a biomarker for inflammation, along with family history of CHD, can be
      added to the parameters of the FRS in the Reynolds Risk Score to yield a more
      refined 10-year CHD risk. Various other biomarkers also can be used. Patients
      with elevated urinary albumin have higher rates of CHD events, though the
      incremental yield of adding urinary albumin provides only minor improvements in
      risk assessment compared with the FRS. Elevated levels of lipoprotein (a) [Lp(a)]
      also predict increased risk of CHD, and some guidelines recommend Lp(a) testing
      for patients with strong family histories of premature CHD. Another biomarker is
      platelet-activating factor acetylhydrolase (Lp-PLA2). Elevated levels indicate
      increased risk, and some recommendations suggest a lower goal level for low
      density lipoprotein with statin therapy when Lp-PLA2 levels are high. Finally,
      genome-wide association studies for genetic risk of CHD currently are not
      recommended, but such tests likely will be useful within the next few years. 

PMID- 24936715
TI  - Cardiac risk factors: environmental, sociodemographic, and behavioral
      cardiovascular risk factors.
AB  - Several environmental exposures are associated with increased risk of coronary
      heart disease (CHD). Exposure to secondhand smoke may increase the risk by as
      much as 25% to 30%. Exposure to third hand smoke, residual components of tobacco
      smoke that remain in the environment after a cigarette is extinguished, also
      appears to increase risk. These residual components can remain in rooms and
      automobiles for up to 30 years and enter the body through the skin or via
      inhalation or ingestion. Exposure to particulate matter air pollution from
      automobile emissions, power plants, and other sources is yet another
      environmental risk factor for CHD, resulting in tens of thousands of deaths
      annually in the United States. Exposure to other environmental toxins,
      particularly bisphenol A and phthalates, also has been linked to CHD. There are
      sociodemographic risks for CHD, with numerous studies showing that lower
      socioeconomic status is associated with higher risk. Behavioral risk factors
      include poor diet, such as frequent consumption of fast food and processed meals;
      sleep disturbance; and psychological stress, particularly related to marital or
      work issues. Finally, although high alcohol consumption is associated with
      increased CHD risk, moderate alcohol consumption (ie, less than 1 to 2
      drinks/day), particularly of wine and possibly beer, appears to reduce the risk.

PMID- 24936716
TI  - Cardiac risk factors: noninvasive testing to detect coronary heart disease.
AB  - Patients with acute chest pain should be assessed first for the likelihood of
      acute coronary syndrome using the Thrombolysis in Myocardial Infarction score or
      the Agency for Health Care Policy and Research criteria. If assessment indicates
      high risk, the patient should be admitted to the hospital. Low- and intermediate
      risk patients whose chest pain has ceased and who have normal or unchanged
      electrocardiograms and troponin levels can be monitored for 6 to 8 hours. If the
      patient then develops recurrent chest pain, electrocardiographic changes, or
      increasing biomarker levels, hospital admission is warranted. If not, further
      testing is indicated to determine if coronary heart disease is present. Testing
      can include exercise treadmill tests, nuclear imaging, or stress
      echocardiography. Coronary computed tomographic angiography and magnetic
      resonance angiography currently are not standard tools for this testing. Testing
      also is sometimes obtained for asymptomatic outpatients with intermediate risk of
      coronary heart disease, with the goal of reclassifying them in low- or high-risk
      categories. Carotid intima-media thickness, ankle-brachial index, coronary artery
      calcium scores, stress tests, coronary computed tomographic angiography, and
      magnetic resonance angiography have been suggested for this purpose, but they
      only result in reclassification of small percentages of patients and are not
      recommended routinely. 

PMID- 24936717
TI  - Cardiac risk factors: new cholesterol and blood pressure management guidelines.
AB  - The 2013 American College of Cardiology/American Heart Association cholesterol
      guidelines depart from low-density lipoprotein (LDL) treatment targets and
      recommend treating four specific patient groups with statins. Statins are the
      only cholesterol-lowering drugs with randomized trial evidence of benefit for
      preventing atherosclerotic cardiovascular disease (ASCVD). The groups are
      patients with clinical ASCVD; patients ages 40 to 75 years with diabetes and LDL
      of 70 to 189 mg/dL but no clinical ASCVD; patients 21 years or older with LDL
      levels of 190 mg/dL or higher; and patients ages 40 to 75 years with LDL of 70 to
      189 mg/dL without clinical ASCVD or diabetes but with 10-year ASCVD risk of 7.5%
      or higher. Ten-year ASCVD risk may be calculated using the Pooled Cohort
      Equations. The Eighth Joint National Committee (JNC 8) guidelines for blood
      pressure management recommend a blood pressure goal of less than 140/90 mm Hg for
      all adults except those 60 years or older. For the latter group, the JNC 8
      recommends a systolic blood pressure goal of less than 150 mm Hg. In another
      notable change from prior guidelines, the JNC 8 recommends relaxing the systolic
      blood pressure goal for patients with diabetes and chronic kidney disease to less
      than 140 mm Hg from less than 130 mm Hg. 

PMID- 24936718
TI  - High-power thulium laser vaporization of the prostate: short-term outcomes of
      safety and effectiveness.
AB  - INTRODUCTION: The thulium laser was introduced in 2005 for the treatment of
      benign prostatic hyperplasia (BPH). Enucleation studies from outside North
      America show comparable efficacy and lower morbidity to transurethral resection
      of the prostate. A few studies exist describing outcomes of vaporization, the
      most commonly used technique for urologists. We present our 3-month outcomes of
      thulium laser vaporization of the prostate (ThuVP). MATERIALS AND METHODS: From
      December 2010 to October 2013, 68 men underwent ThuVP using the 150 W
      CyberTM((r)). Data were collected on demographics, comorbidities, intraoperative
      measures, complications, serum parameters, maximum flow rate (Qmax), postvoid
      residual (PVR), International Prostate Symptom Score (IPSS), quality-of-life
      (QoL) score, and prostate-specific antigen. Patients were evaluated at 1 week, 1
      month, and 3 months postoperatively. Nine patients were excluded for known
      prostate cancer. RESULTS: The mean age was 66+/-10 years, with a mean prostate
      size of 57+/-30 mL. At baseline, the mean IPSS was 19.9+/-8.0, QoL score was
      4.5+/-1.1, Qmax was 5.2+/-4.5 mL/sec, and PVR was 220+/-397 mL. The mean laser
      time was 35+/-18 minutes, and energy used was 234+/-139 kJ. Forty-seven (78%)
      patients were discharged the day of surgery. No blood transfusions were
      administered with a mean drop in hemoglobin of 0.7+/-0.8 g/dL (p<0.05). There
      were no Clavien grade>=III complications within 30 days of surgery. Six (10%)
      patients were diagnosed with urinary tract infection. Significant improvements
      from baseline were seen in Qmax, PVR, IPSS, and QoL score. All 15 patients who
      were in retention were voiding at the last follow-up. CONCLUSIONS: Thulium laser
      vaporization of the prostate appears to be a safe and effective outpatient
      technique for the treatment of BPH with durable outcomes at 3 months.

PMID- 24936720
TI  - Evaluation of renal mass biopsy risk stratification algorithm for robotic partial
      nephrectomy--could a biopsy have guided management?
AB  - PURPOSE: We evaluated a published biopsy directed small renal mass management
      algorithm using a large cohort of patients who underwent robotic partial
      nephrectomy for tumors 4 cm or smaller. MATERIALS AND METHODS: A simplified
      algorithm of biopsy directed small renal mass management previously reported
      using risk stratified biopsies was applied to 1,175 robotic partial nephrectomy
      cases from 5 academic centers. A theoretical assumption was made of perfect
      biopsies that were feasible for all patients and had 100% concordance to final
      pathology. Pathology risk groups were benign, favorable, unfavorable and
      intermediate. The algorithm assigned favorable or intermediate tumors smaller
      than 2 cm to active surveillance and unfavorable or intermediate 2 to 4 cm tumors
      to treatment. Higher surgical risk patients were defined as ASA(r) 3 or greater
      and age 70 years or older. RESULTS: Patients were assigned to the pathology risk
      groups of benign (23%), favorable (13%), intermediate (51%) and unfavorable
      (12%). Patients were also assigned to the management groups of benign pathology
      (275, 23%), active surveillance (336, 29%) and treatment (564, 48%). Most of the
      611 (52%) patients in the benign or active surveillance groups were low surgical
      risk and had safe treatment (2.6% high grade complications). A biopsy may not
      have been feasible or accurate in some tumors that were anterior (378, 32%),
      hilar (93, 7.9%) or less than 2 cm (379, 32%). Of 129 (11%) high surgical risk
      patients the biopsy algorithm assigned 70 (54%) to benign or active surveillance
      groups. CONCLUSIONS: The theoretical application of a biopsy driven, risk
      stratified small renal mass management algorithm to a large robotic partial
      nephrectomy database suggests that about half of the patients might have avoided
      surgery. Despite the obvious limitations of a theoretical assumption of all
      patients receiving a perfect biopsy, the data support the emerging role of renal
      mass biopsies to guide management, particularly in high surgical risk patients.

PMID- 24936721
TI  - Open conversion during minimally invasive radical prostatectomy: impact on
      perioperative complications and predictors from national data.
AB  - PURPOSE: Despite the increased use of minimally invasive radical prostatectomy,
      open conversion may occur due to surgical complications, surgeon inexperience or
      failure to progress. We used nationally representative data to quantify the
      impact of open conversion compared to nonconverted minimally invasive radical
      prostatectomy and open radical prostatectomy, and identify predictors of open
      conversion. MATERIALS AND METHODS: Years 2004 to 2010 of the Nationwide Inpatient
      Sample were queried for patients who underwent radical prostatectomy to analyze
      the association of open conversion during minimally invasive radical
      prostatectomy with Clavien complications. Multivariate regression models yielded
      significant predictors of open conversion. RESULTS: From 2004 to 2010, 134,398
      (95% CI 111,509-157,287) minimally invasive radical prostatectomies were
      performed with a 1.8% (95% CI 1.4-2.1) open conversion rate, translating to 2,360
      (95% CI 2,001-2,720) conversions. Open conversion cases had a longer length of
      stay (4.17 vs 1.71 days, p <0.001) and higher hospital charges ($51,049 vs
      $37,418, p <0.001) than nonconverted cases. Of open conversion cases 45.2%
      experienced a complication vs 7.2% and 12.9% of minimally invasive radical
      prostatectomy and open radical prostatectomy cases, respectively (p <0.001).
      After adjusting for age and comorbidities, open conversion was associated with
      significantly increased odds of a Clavien grade 1, 2, 3 and 4 complication
      compared to nonconverted minimally invasive radical prostatectomy and open
      radical prostatectomy (OR range 2.913 to 15.670, p <0.001). Significant
      multivariate predictors of open conversion were obesity (OR 1.916), adhesions (OR
      3.060), anemia (OR 5.692) and surgeon volume for minimally invasive radical
      prostatectomy less than 25 cases per year (OR 7.376) (all p <0.01). CONCLUSIONS:
      Open conversion during minimally invasive radical prostatectomy is associated
      with a higher than expected increase in complications compared to open radical
      prostatectomy and minimally invasive radical prostatectomy after adjusting for
      age and comorbidities. External validation of predictors of open conversion may
      prove useful in minimizing open conversion during minimally invasive radical
      prostatectomy.

PMID- 24936722
TI  - Cystectomy for refractory hemorrhagic cystitis: contemporary etiology,
      presentation and outcomes.
AB  - PURPOSE: We evaluate the clinical presentation, management and outcomes of
      patients undergoing cystectomy for refractory hemorrhagic cystitis. MATERIALS AND
      METHODS: We identified 21 patients with refractory hematuria treated with
      cystectomy at our institution between 2000 and 2012. Clot evacuation, bladder
      fulguration and bladder irrigation had failed in all patients before cystectomy.
      In addition, 45% of patients had received prior intravesical therapy
      (aminocaproic acid, alum or formalin), hyperbaric oxygen therapy (25%),
      nephrostomy tube placement for attempted urinary diversion (15%) and/or selective
      bladder angioembolization (5%). RESULTS: Median patient age at surgery was 77
      years (IQR 72, 80) and 81% (17 of 21) of patients were male. The most common
      etiology for hemorrhagic cystitis was prior radiation therapy for prostate cancer
      (17, 81%). Median time from receipt of radiation to cystectomy in these patients
      was 91 months (IQR 73, 125). Median ASA(r) (American Society of
      Anesthesiologists) score at cystectomy was 3 and median preoperative hemoglobin
      was 10.2 gm/dl. Median length of stay after cystectomy was 10 days (IQR 7, 19).
      Severe (Clavien grade III to V) complications were noted in 42% of patients (8 of
      19) and the 90-day mortality rate in this cohort was 16% (3 of 19). With a median
      postoperative followup of 13 months (IQR 4, 21), the 1 and 3-year overall
      survival was 84% and 52%, respectively. CONCLUSIONS: Cystectomy for hemorrhagic
      cystitis is associated with a high risk of perioperative complications and
      mortality, consistent with the baseline clinical status of this patient cohort
      and, as such, should remain a last resort to control bleeding after failure of
      conservative measures.

PMID- 24936723
TI  - Spin excitations of ferronematic order in underdoped cuprate superconductors.
AB  - High-temperature superconductors exhibit a characteristic hourglass-shaped
      spectrum of magnetic fluctuations which most likely contribute to the pairing
      glue in the cuprates. Recent neutron scattering experiments in strongly
      underdoped compounds have revealed a significant low energy anisotropy of these
      fluctuations which we explain by a model in which topological defects of the
      antiferromagnet clump to producing domain wall segments with ferronematic order.
      This state does not invoke global charge order but breaks C4 rotational and
      inversion symmetry. The incommensurability of the low doping charge-disordered
      state is in good agreement with experiment and interpolates smoothly with the
      incommensurability of the stripe phase at higher doping. Within linear spin-wave
      theory the dynamic structure factor is in very good agreement with inelastic
      neutron scattering data and can account for the observed energy dependent
      anisotropy. 

PMID- 24936724
TI  - Time-resolved excited state energetics of the solvated electron in sodium-doped
      water clusters.
AB  - The energetics and dynamics of the first electronically excited state of solvated
      electron in sodium-doped water clusters has been studied, by means of time
      resolved electron spectra created in a pump-probe fs-laser experiment. The Na ...
      (H2O)n clusters were excited by pulses at a wavelength of 795 nm, while
      ionization was achieved at a wavelength of 398 nm, and the overall cross
      correlation fwhm was about 50 fs. Mass-resolved electron spectra were taken using
      photoelectron-photoion coincidence (PEPICO) spectroscopy for cluster sizes
      ranging from n = 1 up to 22. The electron spectra give new insights into the
      dynamics of the excited state of solvated electrons in Na ... (H2O)n clusters.
      These dynamics are compared to known results for water cluster anions. In both
      cases, the observed dynamics are a combination of solvent rearrangement and
      internal energy conversion. 

PMID- 24936725
TI  - [Intestinal microbiota and cardiometabolic risk: mechanisms and diet modulation].
AB  - The gut microbiota obtained after birth is composed of a large range of bacteria
      that play different roles in the human host, such as nutrient uptake, protection
      against pathogens and immune modulation. The intestinal bacterial content is not
      completely known, but it is influenced by internal, and mainly by external
      factors, which modulate its composition and function. Studies indicate that the
      gut microbiota differs in lean and obese individuals, and in individuals with
      different food habits. There is evidence that the relationship between diet,
      inflammation, insulin resistance, and cardiometabolic risk are, in part, mediated
      by the composition of intestinal bacteria. Knowledge about the gut microbiota may
      result in different strategies to manipulate bacterial populations and promote
      health. This review discusses the relevance of understanding the role of dietary
      factors or patterns in the composition of the microbiota, as well as
      pathophysiological mechanisms of chronic metabolic diseases, and the potential of
      prebiotics and probiotics on the cardiometabolic risk profile. 

PMID- 24936726
TI  - [The use of FISH on buccal smear to investigate mosaicism with a 45,X cell line:
      study on healthy men and patients with disorders of sex development].
AB  - OBJECTIVE: To verify whether fluorescence in situ hybridization (FISH) of cells
      from the buccal epithelium could be employed to detect cryptomosaicism with a
      45,X lineage in 46,XY patients. SUBJECTS AND METHODS: Samples of nineteen 46,XY
      healthy young men and five patients with disorders of sex development (DSD), four
      45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on
      interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to
      investigate the proportion of nuclei containing only the signal of the X
      chromosome. RESULTS: The frequency of nuclei containing only the X signal in the
      two tissues of healthy men did not differ (p = 0.69). In all patients with DSD
      this frequency was significantly higher, and there was no difference between the
      two tissues (p = 0.38), either. CONCLUSIONS: Investigation of mosaicism with a
      45,X cell line in patients with 46,XY DSD or sterility can be done by FISH
      directly using cells from the buccal epithelium.

PMID- 24936727
TI  - Effects of supplementation with omega-3 on insulin sensitivity and non-esterified
      free fatty acid (NEFA) in type 2 diabetic patients.
AB  - OBJECTIVE: The aim of this study was to determine the role of omega-3
      supplementation on NEFA concentration, insulin sensitivity and resistance, and
      glucose and lipid metabolism in type 2 diabetic patients. SUBJECTS AND METHODS:
      Forty-four type 2 diabetic patients were randomly recruited into two groups.
      Group A received 4 g/day omega-3 soft gels, and group B received a placebo for 10
      wks. Blood samples were collected after 12-h fast. Physical activity records,
      three-day food records, and anthropometric measurements were obtained from all
      participants at the beginning and end of the study. RESULTS: Omega-3
      supplementation caused a significant reduction in NEFA in the intervention group
      compared with the placebo group (P = 0.009). Additionally, the administration of
      omega-3 resulted in significantly greater changes (Diff) for the intervention
      group in various parameters, such as insulin and Quicki indices compared with the
      placebo group (P < 0.05). CONCLUSIONS: Omega-3 fatty acid supplementation in type
      2 diabetic patients improved insulin sensitivity, probably due to the decrease in
      NEFA concentrations.

PMID- 24936728
TI  - [Accuracy of body fat and waist circumference in predicting metabolic
      abnormalities indicating cardiovascular risk in adolescents].
AB  - OBJECTIVE: To evaluate the performance of percent body fat (%BF) and waist
      circumference (WC) in predicting metabolic abnormalities indicating
      cardiovascular risk in adolescents. SUBJECTS AND METHODS: Cross-sectional study
      with a probabilistic sample of 573 adolescents aged 12 to 19 years from state
      public schools in Niteroi, RJ. The Receiver Operating Characteristic Curve was
      used to evaluate the accuracy of WC and %BF in predicting alterations in blood
      pressure, lipid profile, and blood glucose. RESULTS: The best %BF cutoff points
      were 21% for boys, and 23% for girls, with sensitivity (SE) and specificity (SP)
      of approximately 60%. The best WC cutoff points were 71 cm for boys, and 66 cm
      for girls (SE: 55% to 70%; SP: 55% to 78%). CONCLUSION: Even the best cutoff
      points misidentified high proportions of adolescents with metabolic
      abnormalities. Caution is recommended in the use of these indicators for
      cardiovascular risk screening in this age group.

PMID- 24936729
TI  - Epicardial adipose tissue thickness and its association with adiponectin in
      metabolic syndrome patients from Merida, Venezuela.
AB  - OBJECTIVE: To study the relationship between epicardial adipose tissue (EAT)
      thickness and plasma levels of adiponectin in Venezuelan patients. SUBJECTS AND
      METHODS: Thirty-one patients diagnosed with metabolic syndrome (study group) and
      27 controls were selected and tested for glycemia, lipids, and adiponectin. EAT
      thickness, ejection fraction, diastolic function, left ventricular mass (LVM),
      and left atrial volume (LAV) were determined by transthoracic echocardiography.
      RESULTS: EAT thickness was greater in metabolic syndrome patients (5.69 +/- 1.12
      vs. 3.52 +/- 0.80 mm; p = 0.0001), correlating positively with body mass index
      (BMI) (r = 0.661; p = 0.0001); waist circumference (WC) (r = 0.664; p = 0.0001);
      systolic (SBP) (r = 0.607; p = 0.0001), and diastolic blood pressure (DBP) (r =
      0.447; p = 0.0001); insulin (r = 0.505; p = 0.0001); Tg/HDL-C ratio (r = 0.447; p
      = 0.0001), non-HDL-C (r = 0.353; p = 0.007); LAV (r = 0.432; p = 0.001), and LVM
      (r = 0.469; p = 0.0001). EAT thickness correlated negatively with adiponectin (r
      = -0.499; p = 0.0001). CONCLUSION: A significant association exists between EAT
      thickness and both metabolic syndrome components and adiponectin concentration, a
      link that might be used as a biomarker for this disease.

PMID- 24936730
TI  - Relation between ultra-sensitive C-reactive protein, diabetes and periodontal
      disease in patients with and without myocardial infarction.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of diabetes and
      periodontal disease in us-CRP, an inflammatory marker in patients with and
      without acute myocardial infarction (AMI). SUBJECTS AND METHODS: A case-control
      study was conducted in 401 subjects aged between 30 and 75 years, living in
      Bogota D.C. (Colombia). Patients arriving at the emergency room of the San
      Ignacio University Hospital with AMI were included into the case group. The
      control group was defined as those subjects without AMI. The following blood
      tests were performed: complete blood count (CBC), glycemia, total cholesterol,
      triglycerides, cHDL, cLDL, and us-CRP. Patients with infections or antibiotic
      treatment within the last three months, who had received periodontal treatment
      within the six months prior to the study entry, had oral ulcerations, or less
      than seven teeth were excluded from the study. Periodontal disease was diagnosed
      based on the 1999 Armitage's classification. RESULTS: The mean us-CRP value found
      in diabetic patients with severe chronic periodontitis was 5.31 mg/L (SD 6.82),
      and 2.38 mg/L (SD 4.42) in non-diabetic patients, being statistically significant
      (p = 0.000). CONCLUSION: Diabetes had an impact in periodontal disease and us
      CRP. In patients with AMI, DM and PD considerably increased the us-CRP.

PMID- 24936732
TI  - Fasting ghrelin but not PYY(3-36) is associated with insulin-resistance
      independently of body weight in Wistar rats.
AB  - OBJECTIVE: The objective of this study was to evaluate the association between
      insulin-resistance and fasting levels of ghrelin and PYY in Wistar rats.
      MATERIALS AND METHODS: A total of 25 male Wistar rats, weighing 200-300 g, was
      included in this study. The animals were maintained in cages with a 12/12h light
      dark cycle and fed standard chow and water ad libitum. After 12-h overnight
      fasting, ghrelin, PYY, insulin and glucose values were determined. Insulin
      resistance was assessed by means of the HOMA-IR, which was ranked and the median
      was used as a cut-off value to categorize insulin-resistance. HOMA-IR values
      equal and above 2.62 were considered insulin-resistant (IR) while values below
      2.62 were considered insulin sensitive (IS). Differences between means were
      determined using the Student t-test. Multiple regression and Pearson's
      correlation test were used to evaluate the association between variables.
      RESULTS: HOMA-IR median IQ range values for IS and IR groups were, respectively,
      1.56 (0.89 - 2.16) vs. [4.06 (3.50 - 4.61); p < 0.001]. The IR group presented
      increased levels of fasting ghrelin, PYY and insulin respectively: [50.35 (25.99 
      74.71) pg/mL vs. 12.33 (8.77 - 15.89) pg/mL; p = 0.001]; [54.38 (37.50 - 71.26)
      pg/mL vs. 33.17 (22.34 - 43.99) pg/mL; p = 0.016]; [18.04 (14.48 - 21.60) uU/mL
      vs. 7.09 (4.83 - 9.35) uU/mL; p = 0.001]. Ghrelin, but not PYY, correlated
      linearly and positively with HOMA-IR: ghrelin vs. HOMA-IR (r = 0.52; p = 0.008),
      and PYY vs. HOMA-IR (r = 0.22; p = 0.200). This correlation was independent of
      body weight. CONCLUSION: Fasting ghrelin and PYY serum levels are increased in
      lean, relatively insulin resistant Wistar rats, and this increase is independent
      of weight.

PMID- 24936731
TI  - Effect of treatment with sitagliptin on somatosensory-evoked potentials and
      metabolic control in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effect of sitagliptin on somatosensory-evoked
      potentials (SEPs) and metabolic control in patients with type 2 diabetes mellitus
      without clinical diabetic neuropathy. MATERIALS AND METHODS: Interventional,
      prospective, and open study. Patients with less than six months from the
      diagnosis were included. Examinations of SEPs and laboratory tests at fasting and
      after food stimulation were performed before and after three months of treatment
      with sitagliptin (100 mg/day). RESULTS: There was a reduction in the mean levels
      of HbA1c (P < 0.0001), fasting glucose (P = 0.001), total cholesterol (P =
      0.019), and ALT (P = 0.022). An increase in active GLP-1 was found at the end of
      the study (P = 0.0025). Several SEPs showed statistically significant differences
      when analyzed before and after treatment with sitagliptin. CONCLUSION: The
      results give a glimpse of the possible use of sitagliptin in the treatment of
      some neurodegenerative conditions of the peripheral nervous system, in addition
      to its already established role in glycemic control.

PMID- 24936733
TI  - The rs1893217 (T/C) polymorphism in PTPN2 gene is not associated with type 1
      diabetes mellitus in subjects from Southern Brazil.
AB  - OBJECTIVE: To evaluate the association of the PTPN2 rs1893217 polymorphism with
      T1DM and/or its clinical and laboratory characteristics in a Caucasian population
      from Southern Brazil. SUBJECTS AND METHODS: Four hundred and eighty six patients
      with T1DM and 484 non-diabetic subjects were included in the study. Genotyping of
      the PTPN2 rs1893217 was performed by real-time PCR. RESULTS: Genotype frequencies
      did not differ between T1DM patients and non-diabetic subjects (P = 0.265). The C
      allele was observed in 14.5% of the T1DM sample and 12.2% of the non-diabetic
      group (P = 0.152). Moreover, the frequencies of this variant did not differ
      statistically between T1DM patients and non-diabetic subjects when assuming
      recessive, dominant, or additive inheritance models. The clinical and laboratory
      characteristics of T1DM patients did not differ significantly among the three
      genotypes of the rs1893217 polymorphism, either. CONCLUSION: The PTPN2 rs1893217
      polymorphism is not significantly associated with T1DM in Caucasian subjects from
      Southern Brazil.

PMID- 24936734
TI  - TSH reference range in older adults: a Brazilian study.
AB  - OBJECTIVE: To establish serum TSH reference values for a population of Brazilian
      elderly, and to compare them to those found in the adult population. SUBJECTS AND
      METHODS: Healthy volunteers aged 70 to 85 years, without known thyroid disease or
      risk factors for thyroid dysfunction, who did not use any medication that could
      potentially interfere with TSH, were selected. Subjects with goiter, palpable
      thyroid nodules, anti-thyroperoxidase antibodies, or altered free T4 were
      excluded. The sample consisted of 360 older adults (180 per sex). RESULTS: TSH
      values corresponding to the 2.5th and 97.5th percentile of the sample were 0.2
      and 4.62 mIU/L, respectively. TSH > 2.5 mIU/L was seen in 25.26% of the
      volunteers, > 3 mIU/L in 15.26%, and > 4 mIU/L in 6.1% of them. TSH values were
      slightly higher than those previously reported for adults (18-60 years).
      CONCLUSION: This study suggests an upper limit for normal TSH of approximately
      4.6 mIU/L for the Brazilian elderly population.

PMID- 24936735
TI  - [The importance of memory bias in obtaining age of menarche by recall method in
      Brazilian adolescents].
AB  - OBJECTIVE: To compare the age at menarche obtained by recall method according to
      the time elapsed since the event, in order to verify the importance of the recall
      bias. SUBJECTS AND METHODS: Were evaluated 1,671 girls (7-18 years) at schools in
      Campinas-SP regarding the occurrence of menarche by the status quo method
      (menarche: yes or no) and the recall method (date of menarche, for those who
      mentioned it). The age at menarche obtained by the status quo method was
      calculated by logit, which considers the whole group, and the age obtained by the
      recall method was calculated as the average of the mentioned age at menarche. In
      this group, the age at menarche was obtained by the difference between the date
      of the event and the date of birth. Girls who reported menarche (883, 52.8%) were
      divided into four groups according to the time elapsed since the event. To
      analyze the results, we used ANOVA and logistic regression for the analysis, with
      a significance level of 0.05. RESULTS: The age at menarche calculated by logit
      was 12.14 y/o (95% CI 12.08 to 12.20). Mean ages obtained by recall were: for
      those who experienced menarche within the previous year 12.26 y/o (+/-1.14),
      between > 1-2 years before, 12.29 y (+/-1.22); between > 2-3 years before, 12.23
      y/o (+/-1.27); and more than 3 years before, 11.55y/o (+/-1.24), p < 0.001.
      CONCLUSION: The age at menarche obtained by the recall method was similar for
      girls who menstruated within the previous 3 years (and approaches the age
      calculated by logit); when more than 3 years have passed, the recall bias was
      significant.

PMID- 24936736
TI  - An uncommon case of Marine-Lenhart syndrome.
AB  - The term Marine-Lenhart syndrome describes the association between Graves'
      disease and autonomously functioning thyroid nodules (AFTN), such as toxic
      adenoma or toxic multinodular goiter. The two diseases may coexist or may be
      present at different moments in the same patient. In the literature, there are
      many reports on the development of Graves' disease after radioiodine treatment
      for AFTN, but very little information may be found on the occurrence of AFTN
      after radioiodine therapy for Graves' disease. We describe here the case of a
      female patient with Graves' disease who was successfully treated with radioiodine
      for Graves' disease, returning to normal thyroid function. Three years later,
      biochemical analysis and ultrasound examination identified a thyroid nodule that
      progressively increased in size. The 99mTc-pertechnetate scintigraphy showed avid
      uptake in the right lobule, which corresponded to a nodular lesion consistent
      with AFTN.

PMID- 24936737
TI  - Malignant solitary fibrous tumor of the thyroid: a case-report and review of the
      literature.
AB  - Solitary fibrous tumor (SFT) is an uncommon spindle-cell neoplasm that most often
      involves the pleura, rarely occurring in extra-thoracic locations. Twenty-six
      cases of SFT arising in the thyroid gland have been described. We report a case
      of a 60-year-old woman presenting an 8-month history of enlargement of the neck
      associated with dysphagia. The patient underwent a right hemithyroidectomy and
      SFT of the thyroid was diagnosed. Immunohistochemistry showed positivity for CD34
      marker, and the high number of mitoses and the presence of cellular atypia
      suggested that the tumor was malignant. To our knowledge, this is the second case
      of malignant SFT of the thyroid gland ever reported. Due to the rarity of these
      tumors, the indication of adjuvant therapy and prognosis are uncertain. Long-term
      follow-up after surgical resection seems to be advisable. 

PMID- 24936738
TI  - Sensor-augmented pump and Down syndrome: a new tool in tricky patients.

PMID- 24936739
TI  - Differential regulation of MeCP2 and PP1 in passive or voluntary administration
      of cocaine or food.
AB  - Cocaine exposure induces changes in the expression of numerous genes, in part
      through epigenetic modifications. We have initially shown that cocaine increases
      the expression of the chromatin remodeling protein methyl-CpG binding protein 2
      (MeCP2) and characterized the protein phosphatase-1Cbeta (PP1Cbeta) gene, as
      repressed by passive i.p. cocaine injections through a Mecp2-mediated mechanism
      involving de novo DNA methylation. Both proteins being involved in learning and
      memory processes, we investigated whether voluntary cocaine administration would
      similarly affect their expression using an operant self-administration paradigm.
      Passive and voluntary i.v. cocaine intake was found to induce Mecp2 and to
      repress PP1Cbeta in the prefrontal cortex and the caudate putamen. This
      observation is consistent with the role of Mecp2 acting as a transcriptional
      repressor of PP1Cbeta and shows that passive intake was sufficient to alter their
      expression. Surprisingly, striking differences were observed under the same
      conditions in food-restricted rats tested for food pellet delivery. In the
      prefrontal cortex and throughout the striatum, both proteins were induced by food
      operant conditioning, but remained unaffected by passive food delivery. Although
      cocaine and food activate a common reward circuit, changes observed in the
      expression of other genes such as reelin and GAD67 provide new insights into
      molecular mechanisms differentiating neuroadaptations triggered by each
      reinforcer. The identification of hitherto unknown genes differentially regulated
      by drugs of abuse and a natural reinforcer should improve our understanding of
      how two rewarding stimuli differ in their ability to drive behavior. 

PMID- 24936740
TI  - Prioritising in situ conservation of crop resources: a case study of African
      cowpea (Vigna unguiculata).
AB  - Conserving crop wild relatives (CWR) is critical for maintaining food security.
      However, CWR-focused conservation plans are lacking, and are often based on the
      entire genus, even though only a few taxa are useful for crop improvement. We
      used taxonomic and geographic prioritisation to identify the best locations for
      in situ conservation of the most important (priority) CWR, using African cowpea
      (Vigna unguiculata (L.) Walp.) as a case study. Cowpea is an important crop for
      subsistence farmers in sub-Saharan Africa, yet its CWR are under-collected, under
      conserved and under-utilised in breeding. We identified the most efficient sites
      to focus in situ cowpea CWR conservation and assessed whether priority CWR would
      be adequately represented in a genus-based conservation plan. We also
      investigated whether priority cowpea CWR are likely to be found in existing
      conservation areas and in areas important for mammal conservation. The genus
      based method captured most priority CWR, and the distributions of many priority
      CWR overlapped with established conservation reserves and targets. These results
      suggest that priority cowpea CWR can be conserved by building on conservation
      initiatives established for other species. 

PMID- 24936741
TI  - Age-related toxicity in patients with rhabdomyosarcoma: a report from the
      children's oncology group.
AB  - On the Fourth Intergroup Rhabdomyosarcoma study, older children experienced
      excessive neurotoxicity, whereas younger children had increased myelosuppression.
      The purpose of this study was to determine whether the same pattern of toxicity
      was seen on the successor study when use of growth factor was required and dosing
      of chemotherapy was different by performing a retrospective cohort analysis on
      patients treated on Children's Oncology Group protocol D9803. Toxicity data were
      analyzed by stratifying children into 4 age groups. The frequency of grade 3/4
      neurotoxicity, myelosuppression, infection, and mucositis was predicted for each
      age group. The cumulative doses of vincristine and cyclophosphamide administered
      were measured as percent of protocol-prescribed dose. Adolescents (aged 15+) were
      more likely to experience neurotoxicity compared with younger patients (odds
      ratio, 3.6; P<0.0001). There was no difference in myelosuppression, infection, or
      mucositis. The mean percent protocol-prescribed doses administered for
      vincristine and cyclophosphamide did not differ much by age group. Adolescents
      experienced more neurotoxicity with vincristine compared with younger patients.
      No differences in other toxicities were observed between age groups. As
      adolescents received at least 85% of protocol-prescribed doses of vincristine, it
      is difficult to attribute the poorer survival in this age group to inadequate
      protocol-delivered therapy. 

PMID- 24936742
TI  - Health status and quality of life of long-term survivors of childhood acute
      leukemia: the impact of central nervous system irradiation.
AB  - We evaluated the impact of central nervous system irradiation (CNSI) on long-term
      health status and quality of life (QoL) of childhood lymphoblastic leukemia
      survivors included in the French L.E.A. (Childhood and Adolescent Leukemia)
      multicentric cohort. QoL was self-reported in adults and assessed by parents in
      children and adolescents, using adapted questionnaires. From 2004 to 2009, 630
      nongrafted patients were assessed after 11.8+/-6.3 years from diagnosis. Patients
      receiving CNSI (18.6%) or chemotherapy alone (81.4%) were compared. The risk of
      having long-term physical effects was increased with CNSI (odds ratio=3.3; 95%
      confidence interval, 1.8-5.9), especially regarding growth failure, second tumor,
      cataract, and overweight. QoL did not differ significantly according to the
      treatment received, despite a tendency toward lower scores with CNSI in children
      and adolescents (summary score 63.6+/-13.3 vs. 71.7+/-12.4, P=0.14). Compared
      with French norms, adult survivors had an impaired QoL, especially in mental
      domains (mental composite score 45.2+/-9.8 vs. 47.9+/-2.1, P<0.001). In pediatric
      survivors, QoL was not impaired and even tended to be higher than population
      norms (summary score 71.7+/-12.4 vs. 70.0+/-4.2, P=0.054), mainly in social and
      relational domains. In conclusion, QoL seems to be impaired by the trauma of a
      life-threatening illness in childhood, as well as by the treatment received. 

PMID- 24936743
TI  - Leukapheresis in management of hyperleukocytosis in children's leukemias.
AB  - We describe 16 leukapheresis (LK) procedures performed in 7 children with
      different types of leukemia and hyperleukocytosis. We also provide an analysis of
      previously published experiences of pediatric LK. Median age and body weight of
      patients were 12.3 years (range, 0.2 to 16.7 y) and 49 kg (range, 5 to 61 kg).
      Immediate pre-first-LK median white blood cell count was 478*10/L (108*10/L to
      988*10/L). All cytoreduction were performed on Cobe Spectra cell separator. Sixty
      eight percent of procedures were performed with peripheral veins. Extracorporeal
      line had been primed with red blood cell for 31% of LK. The median decrease in
      white blood cell count after each LK was 33% (0% to 69%), and overall decrease
      after completion of LK procedures was 62% (11% to 94%). Only minor clinical
      adverse events and no metabolic complication were attributable to LK. No more
      clinical symptom of hyperleukocytosis was observed after completion of LK
      procedures. Our findings are consistent with reported results in other pediatric
      series: LK is a well-tolerated procedure that can be safely performed with an
      experienced pediatric team even on the smallest children. 

PMID- 24936745
TI  - Membrane Interaction and Protein Kinase C-C1 Domain Binding Properties of 4
      Hydroxy-3-(hydroxymethyl) Phenyl Ester Analogues.
AB  - Protein kinase C (PKC)-C1 domain targeted regulator development is considered as
      a potential therapeutic strategy for the treatment of cancer and immunological
      and other diseases. Efforts are underway to synthesize small molecules to achieve
      higher specificity for the C1-domain than the natural activator, diacylglycerols
      (DAGs). In this regard, we conveniently synthesized 4-hydroxy-3-(hydroxymethyl)
      phenyl ester analogues and measured in vitro C1-domain binding properties. We
      also investigated different physicochemical properties of the synthesized
      molecules, including aggregation behavior in aqueous solution and interaction
      with lipid bilayers, and others with an aim for better understanding of their C1
      domain binding properties. The results showed that the membrane-active compounds
      aggregate in aqueous solution at a reasonably lower concentration and strongly
      interact with the lipid bilayer. The hydrophilic part of the compounds localize
      at the bilayer/water interface and accessible for C1-domain binding. Biophysical
      studies revealed that the hydroxyl, hydroxymethyl, and carbonyl groups and acyl
      chain length are important for their interaction with the C1-domain. The potent
      compound showed more than 10-fold stronger binding affinity for the C1-domains
      than DAG under similar experimental conditions. Therefore, our findings reveal
      that these ester analogues represent an attractive group of C1-domain ligands
      that can be further structurally modified to improve their binding and activity.

PMID- 24936746
TI  - Publishing data from electronic health records while preserving privacy: a survey
      of algorithms.
AB  - The dissemination of Electronic Health Records (EHRs) can be highly beneficial
      for a range of medical studies, spanning from clinical trials to epidemic control
      studies, but it must be performed in a way that preserves patients' privacy. This
      is not straightforward, because the disseminated data need to be protected
      against several privacy threats, while remaining useful for subsequent analysis
      tasks. In this work, we present a survey of algorithms that have been proposed
      for publishing structured patient data, in a privacy-preserving way. We review
      more than 45 algorithms, derive insights on their operation, and highlight their
      advantages and disadvantages. We also provide a discussion of some promising
      directions for future research in this area. 

PMID- 24936747
TI  - Analysis of in situ electric field and specific absorption rate in human models
      for wireless power transfer system with induction coupling.
AB  - This study investigates the specific absorption rate (SAR) and the in situ
      electric field in anatomically based human models for the magnetic field from an
      inductive wireless power transfer system developed on the basis of the
      specifications of the wireless power consortium. The transfer system consists of
      two induction coils covered by magnetic sheets. Both the waiting and charging
      conditions are considered. The transfer frequency considered in this study is 140
      kHz, which is within the range where the magneto-quasi-static approximation is
      valid. The SAR and in situ electric field in the chest and arm of the models are
      calculated by numerically solving the scalar potential finite difference
      equation. The electromagnetic modelling of the coils in the wireless power
      transfer system is verified by comparing the computed and measured magnetic field
      distributions. The results indicate that the peak value of the SAR averaged over
      a 10 g of tissue and that of the in situ electric field are 72 nW kg(-1) and 91
      mV m(-1) for a transmitted power of 1 W, Consequently, the maximum allowable
      transmitted powers satisfying the exposure limits of the SAR (2 W kg(-1)) and the
      in situ electric field (18.9 V m(-1)) are found to be 28 MW and 43 kW. The
      computational results show that the in situ electric field in the chest is the
      most restrictive factor when compliance with the wireless power transfer system
      is evaluated according to international guidelines. 

PMID- 24936749
TI  - Organic magnetic diradicals (radical-coupler-radical): standardization of
      couplers for strong ferromagnetism.
AB  - The intramolecular magnetic coupling constant (J) values of sets of diradicals
      linked to bis-DTDA, OVER, and NN radicals (DTDA, OVER, and NN groups) through an
      aromatic coupler were studied by unrestricted density functional theory
      calculations (UB3LYP/6-311++G(d,p)). Among 15 aromatic couplers, 9 compounds with
      an odd number of carbon atoms along its spin coupling path were found to interact
      ferromagnetically upon coupling with bisradicals while the other 6 couplers with
      an even number of carbon atoms along its spin coupling path give rise to
      antiferromagnetic coupling. The overall trends in the strength of magnetic
      interactions of aromatic couplers were preserved for DTDA, OVER, and NN groups so
      that the trend can be utilized as an index for the magnetic strength of a given
      coupler. It was found that the differences in the nucleus-independent chemical
      shift (NICS), bond order of connecting bonds, and Mulliken atomic spin density at
      connected atoms between triplet and BS states are closely related to the
      intramolecular magnetic behavior. 2,4- and 2,5-phosphole couplers exhibit the
      strongest intramolecular ferromagnetic and antiferromagnetic interactions among
      15 aromatic couplers when linked to diverse bisradicals. 

PMID- 24936750
TI  - Symptom assessment in pediatric oncology: how should concordance between
      children's and parents' reports be evaluated?
AB  - BACKGROUND: Clinical evaluations in pediatric oncology are often triadic,
      involving children or adolescents, parents, and clinicians. However, few studies
      have evaluated the concordance between children's and parents' reports of symptom
      occurrence. OBJECTIVES: The purposes of this study were to evaluate the
      concordance between children's and parents' symptom reports during the week of
      chemotherapy administration using 5 statistical approaches and determine which
      factors are associated with higher levels of dyadic concordance. METHODS:
      Independent assessments of symptom occurrence were obtained from children and
      adolescents with cancer (n = 107) and their parents using the Memorial Symptom
      Assessment Scale 10-18. Concordance was assessed using (1) percentage of overall
      agreement, (2) Cohen kappa coefficients, (3) McNemar tests, (4) positive
      percentage agreement, and (5) negative percentage agreement. RESULTS: For each
      dyad, an average of 20 of the 31 symptom reports were concordant. Using
      children's reports as the "gold standard," parents rarely underestimated the
      children's symptoms. However, compared with children's reports, parents
      overestimated 7 symptoms. Advantages and disadvantages of each of the statistical
      approaches used to evaluate concordance are described in this article.
      CONCLUSIONS: A variety of statistical approaches are needed to obtain a thorough
      evaluation of the concordance between symptom reports. Discordance was most
      common for symptoms that children refuted, particularly psychosocial symptoms.
      IMPLICATIONS FOR PRACTICE: Clinicians need to interview children and adolescents
      along with their parents about the occurrence of symptoms and evaluate discrepant
      reports. Effective approaches are needed to improve communication between
      children and parents to improve symptom assessment and management.

PMID- 24936751
TI  - Psychological distress between young adult female survivors of childhood cancer
      and matched female cohorts surveyed in the adolescent health study.
AB  - BACKGROUND: The psychological health of childhood cancer survivors is an
      essential treatment outcome. Female survivors are a subgroup of survivors with an
      increased risk for poor psychological outcomes. OBJECTIVE: This study compared
      psychological distress in young adult female survivors of childhood cancer with
      that in young adult females in the general population with no history of
      childhood cancer. Psychological distress was measured by assessing respondents'
      subjective degree of depressive symptoms, anxiety, and somatization. METHODS: The
      study was a secondary data analysis. The sample was drawn from the National
      Longitudinal Study of Adolescent Health, which used a representative, probability
      based sampling technique. The sample included 66 young adult female survivors of
      childhood cancer and 8186 young adult females with no history of cancer.
      Randomized, nonparametric testing was used to construct 10 000 different age
      matched female cohort samples from the general population. RESULTS: Young adult
      female survivors of childhood cancer had more depressive symptoms (P < .05) as
      compared with matched cohorts with 589 of the 10,000 matched samples. There were
      no statistically significant differences between the cancer survivors and the
      matched cohort groups on anxiety and somatization symptoms. CONCLUSION: Young
      adult female survivors of childhood cancer are at an increased risk of
      experiencing depression, which can decrease their psychological functioning and
      emotional well-being. IMPLICATIONS FOR PRACTICE: Healthcare professionals who
      care for these cancer survivors need to be aware that female survivors are at
      risk for depression and should screen and refer accordingly.

PMID- 24936744
TI  - Mercaptopurine/Methotrexate maintenance therapy of childhood acute lymphoblastic
      leukemia: clinical facts and fiction.
AB  - The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX)
      maintenance therapy are poorly understood, but the benefits of several years of
      myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well
      proven. Currently, there is no international consensus on drug dosing. Because of
      significant interindividual and intraindividual variations in drug disposition
      and pharmacodynamics, vigorous dose adjustments are needed to obtain a target
      degree of myelosuppression. As the normal white blood cell counts vary by
      patients' ages and ethnicity, and also within age groups, identical white blood
      cell levels for 2 patients may not reflect the same treatment intensity.
      Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can
      identify nonadherent patients, but therapeutic target levels remains to be
      established. A rise in serum aminotransferase levels during maintenance therapy
      is common and often related to high levels of methylated 6MP metabolites.
      However, except for episodes of hypoglycemia, serious liver dysfunction is rare,
      the risk of permanent liver damage is low, and aminotransferase levels usually
      normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose
      increments should lead to either leukopenia or a rise in aminotransferases, and
      if neither is experienced, poor treatment adherence should be considered. The
      many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and
      toxicity have precluded implementation of pharmacogenomics into treatment, the
      sole exception being dramatic 6MP dose reductions in patients who are homozygous
      deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and
      several of its metabolites. In conclusion, maintenance therapy is as important as
      the more intensive and toxic earlier treatment phases, and often more
      challenging. Ongoing research address the applicability of drug metabolite
      measurements for dose adjustments, extensive host genome profiling to understand
      diversity in treatment efficacy and toxicity, and alternative thiopurine dosing
      regimens to improve therapy for the individual patient. 

PMID- 24936753
TI  - [Contributions of Psychiatric Association of Turkey to psychiatric training].

PMID- 24936752
TI  - A review of supportive care interventions to manage distress in young children
      with cancer and parents.
AB  - BACKGROUND: There is a positive relationship between parent and young child
      distress during cancer treatment. Dimensions of parent/child distress are
      multifaceted and associated with family function and quality of life outcomes. A
      critical examination of intervention research is needed to identify how
      dimensions of parent/child distress and related outcomes are being addressed.
      OBJECTIVE: The aims of this study were to summarize and describe supportive care
      intervention research for young children with cancer and parents and to discuss
      implications for family-based intervention research. METHODS: This systematic
      review examined supportive care intervention studies with randomized and
      nonrandomized designs for young children with cancer (aged 3-8 years) and/or
      their parents published between 1991 and 2011. Twenty-two studies that met
      specific inclusion criteria were reviewed to determine intervention type,
      intervention components, targeted outcomes and findings, and whether
      interventions addressed child, parent, or parent/child needs. RESULTS: Most
      interventions focused primarily on procedural support, followed by parent
      education/counseling. Most studies targeted the child or the parent alone; very
      few targeted parent/child dyads. Outcomes focused primarily on child distress,
      anxiety, and pain. Quality of life and coping were rarely measured, and no
      studies examined family function. This body of research is emerging, with most
      interventions in the developmental pilot phase and few efficacy trials.
      CONCLUSIONS: Findings confirm underrepresentation of young children in supportive
      care intervention research and the need for more complex, family-based
      interventions to advance young child intervention research beyond acute,
      procedural distress. IMPLICATIONS FOR PRACTICE: The authors discuss the
      implications of review findings for clinical practice.

PMID- 24936754
TI  - [Prefrontal cortex neurochemical metabolite levels in major depression and the
      effects of treatment: an HMRS study].
AB  - OBJECTIVE: Neuronal degeneration in the prefrontal cortex during depression
      results in altered production of neurochemical metabolites. The aim of the
      present study is to examine changes in neurochemical metabolites in the
      prefrontal cortex and evaluate the effects of psychodrama group therapy and
      pharmacotherapy on neurochemical metabolism in the first episode depression using
      1HMRS methodology. METHOD: Eighteen drug-free female patients with diagnosed
      first-episode major depression according to DSM-IV criteria and 10 healthy female
      subjects were enrolled in the study. The Hamilton Rating of Depression Scale (HAM
      D) was used to asses the severity of depression in each of the study
      participants. Proton magnetic resonance spectroscopy (1HMRS) was applied to the
      right prefrontal cortex both before and after treatment and the concentration of
      N-Asetil Aspartate (NAA), choline (Cho), and creatine (Cr) were measured. All
      patients were prescribed ant-depressant medication at the time of the evaluation
      (essitalopram 10-20 mg/g). In addition, a psychodrama group therapy session was
      conducted in which 10 patients participated in one 3-hour session each week. HAM
      D and 1HMRS were repeated after 16 weeks. RESULTS: Prior to treatment, the HAM-D
      score in the patient group was 14.55+/-4.55 while the HAM-D score was 3.88+/-2.47
      after 16 weeks of treatment. The severity of symptoms among the patient group was
      determined to be mild/moderate. No neurochemical abnormalities were identified in
      the right prefrontal cortex of depressed patients compared to the healthy
      subjects in the baseline measurements and no significant change was observed in
      neurochemical metabolites following treatment with pharmacotherapy or
      pharmacotherapy with group psychotherapy. CONCLUSION: Our results identified no
      neurodegeneration, cell membrane dysfunction, alterations in energy metabolism,
      or altered neurochemical metabolite levels in patients undergoing a first episode
      of mild/moderate depression. Further studies will be needed to evaluate the
      effects of alternate treatments and the presence or absence of neuronal damage
      during follow-up of patients with depression.

PMID- 24936755
TI  - [ADHD in adult psychiatric outpatients: prevalence and comorbidity].
AB  - AIM: This study aimed to investigate the prevalence of attention
      deficit/hyperactivity disorder (ADHD) in adult psychiatric outpatients. Moreover,
      comorbid psychiatric diagnoses in adults with ADHD were determined. Patients with
      and without ADHD were compared regarding DSM Axis I-II comorbidity and
      sociodemographic characteristics. MATERIALS AND METHODS: The study included
      patients that presented for the first time to a psychiatric outpatient clinic
      during a 3-month period and were evaluated for adult ADHD. A sociodemographic
      form, Wender Utah Rating Scale, Turgay's Adult ADD/ADHD Evaluation Scale,
      Structured Clinical Interview I and II, Symptom Check List-90-R, and Beck
      Depression Inventory were administered. RESULTS: The study included 246 patients.
      Among the 39 patients diagnosed with ADHD, 25 were female (64.1%) and 14 were
      male (35.9%), and the mean age was 27.38 +/- 8.3 years. The prevalence of ADHD in
      adult psychiatric patients was 15.9%. Adults with ADHD usually presented due to
      comorbid psychiatric problems; major depression (43%), generalized anxiety
      disorder (23%), and obsessive-compulsive disorder (17%) were the most common
      comorbid diagnoses. Substance abuse (58.9%) and attempted suicide (38.5%) were
      among the most prevalent psychiatric problems. CONCLUSION: The present findings
      show that ADHD is an important comorbidity in adult patients that present to
      psychiatric clinics, and may cause serious mental health problems or complicate
      mental illness.

PMID- 24936756
TI  - [The relationship between the duration of drug use and the bipolar disorder
      patients' sociodemographic and clinical characteristics].
AB  - OBJECTIVE: The purpose of this study was to determine the duration of
      psychotropic drug use in the long-term follow-up of bipolar disorder (BD)
      patients. In addition, this study aimed to investigate their role in the daily
      clinical practice in association with patient sociodemographic and clinical
      characteristics. The overarching goal for this study was to produce results that
      enlighten the development of new treatment strategies. METHOD: Follow-up data
      acquired from the Psychiatry Department of Uludag University Faculty of Medicine
      was used to retrospectively evaluate 151 patients diagnosed with BD. Socio
      demographic data of the patients and information regarding the disease and the
      drugs used were analyzed. RESULTS: Of the patients studied, 57.0% were female
      with a mean age of 41.5+/-12.8. The mean duration of follow-up was 1985.3+/-1933
      [median 1291 (15-9135)] days; euthymic period accounted for 86.0% of this
      duration. Interestingly, incompliance with the treatment triggered the switch to
      mania and ineffective treatment triggered the switch to depression. Medication
      distribution was as follows: 95.4% of the patients received antipsychotic and
      mood stabilizer treatments, 3.3% received only mood stabilizer treatment, and
      1.30% received only antipsychotic treatment. The major findings of this study was
      that many sociodemographic as well as clinical manifestations including, early
      onset (aged <=18 years), unmarried, first episode of mania, those with disease
      not showing seasonal features, psychotic symptoms, history of hospitalization,
      and higher number of manic or hypomanic episodes resulted in increased patient
      prescribed antipsychotic drugs CONCLUSION: Our data suggests that antipsychotic
      drugs are being used more frequently and for longer durations in the treatment of
      BD.

PMID- 24936757
TI  - [Irritability associated with major depressive episodes: its relationship with
      mood disorders and temperament].
AB  - OBJECTIVE: Irritability is a well-known feature of some mood states. Within the
      framework of major depressive episodes (MDEs) irritability has been associated
      with subtypes of depressive mood, personality traits, depressive mixed states,
      and a bipolar diathesis. This study aimed to assess the symptomatology of
      irritable depression and the effect of personality. MATERIALS AND METHODS: The
      study included 93 patients with MDEs, with and without other diagnoses. The
      characteristics and severity of depressive, manic, and anxious symptoms were
      assessed. Irritability was determined using the Irritability, Depression and
      Anxiety Scale outwardly directed irritability subscale (IDA-out). The patients
      were also administered the Multidimensional Assessment of Thymic States and the
      Irritability Questionnaire. Personality was assessed using the Temperament and
      Character Inventory-125 (TCI-125) and the Temperament Evaluation of Memphis,
      Pisa, Paris, and San Diego (TEMPS-A). RESULTS: More of the MDE patients with
      irritability (32.3%) had atypical features (i.e. weight gain and rejection
      sensitivity), guilt, hypomanic symptoms, depressive mixed states, and a personal
      and family history of bipolar disorder than the MDE patients without
      irritability. Irritability was moderately correlated with depression, hypomania,
      anxiety, and emotional reactivity. More of the irritable MDE patients exhibited
      increased novelty seeking, irritable and hyperthymic temperament scores, and had
      lower TCI-125 and TEMPS-A cooperation and harm avoidance scores than those that
      were not irritable. Forward logistic regression analysis showed that there was a
      strong independent association between irritability, and weight gain, irritable
      temperament, depressive mixed states, novelty seeking, and depression.
      CONCLUSIONS: MDE-related irritability was strongly associated with atypical and
      mixed features, which may be indicative of a bipolar diathesis, as well as
      specific temperament characteristics that may be indicative of trait activation.

PMID- 24936758
TI  - [The impact of disease course and type of episodes in bipolar disorder on
      caregiver burden].
AB  - OBJECTIVE: The aim of this study was to determine how the disease course and type
      of episodes in patients with bipolar I disorder (BPD-I) affect caregiver burden.
      MATERIALS AND METHODS: The study was conducted between February and July 2010,
      and included 89 euthymic-state BPD-I patients (55 with a natural course and 34
      with >=1 mixed episode or a rapid cycling course) diagnosed according to DSM-IV
      TR criteria and 89 of their caregivers. The patients were evaluated using a
      sociodemographic clinical form, the Hamilton Depression Rating Scale (HAM-D),
      Young Mania Rating Scale (YMRS), and Global Assessment of Functionality Scale
      (GAFS). The caregivers were evaluated using a sociodemographic form and the Zarit
      Caregiver Burden Interview (ZCBI). RESULTS: In all, 44% of the BPD-I patients'
      caregivers had moderate to severe burden. More of the caregivers of patients with
      rapid cycling or mixed episodes had social relationships negatively affected by
      caregiver burden (P < 0.01). The mean YMRS score was higher in the caregivers
      with moderate to severe burden (P< 0.01). As patient age, YMRS score, number of
      manic episodes, duration of illness, and duration of caregiving during the
      euthymic period increased (P < 0.05) the level of caregiver-perceived dependency
      also increased; as caregiver age and the duration of caregiving increased, the
      perception of economic burden decreased (P< 0.05). CONCLUSION: BPD-I patient
      caregiving, even when patients are in a euthymic state, results in considerable
      caregiver burden. Mixed episodes or rapid cycling increases the severity of
      caregiver burden, as does the number of manic episodes and the presence of
      subsyndromal manic features.

PMID- 24936759
TI  - [The validity and reliability of the Brief-Hypomanic Attitudes and Positive
      Predictions Inventory-Turkish version].
AB  - OBJECTIVE: There has been a great deal of interest in specific dysfunctional
      beliefs that may be associated with susceptibility to mania. The Hypomanic
      Attitudes and Positive Predictions Inventory (HAPPI) was developed by Mansell
      (2006) to identify such beliefs. The present study aimed to measure the
      psychometric properties of the Turkish version of the brief version of the HAPPI
      (Brief-HAPPI-TR). METHOD: The study sample consisted of 115 outpatients with
      bipolar disorder (BD) and 103 healthy controls. Participants were administered
      the Brief-HAPPI-TR, Mood Disorder Questionnaire (MDQ), and Dysfunctional
      Attitudes Scale (DAS). RESULTS: The reverse-scored HAPPI items lowered the alpha
      coefficient and were therefore excluded from the total score. The remaining items
      had high internal consistency for the entire sample (r = 0.84), for the BD group
      (r = 0.83), and for the control group (r = 0.86). The test-retest reliability
      coefficient was moderately high (r = 0.41). Brief-HAPPI-TR scores were
      significantly correlated with MDQ and DAS scores. Finally, Brief-HAPPI-TR was
      able to differentiate between the BD patients and controls. CONCLUSION: Brief
      HAPPI-TR was observed to be valid and reliable for assessing hypomanic attitudes
      in Turkish BD patients in remission. In addition, we think that within the
      cognitive-behavioral paradigm this scale can be used to identify and treat
      dysfunctional cognitions in Turkish BD patients.

PMID- 24936760
TI  - [The concept of mental health deterioration in light of decisions by higher
      judicial bodies].
AB  - Important arrangements were made to protect an individuals' sexual safety in the
      Turkish Penal Code. During judgments of sexual crimes, the witnesses of medical
      experts are usually used for evidence collection and for researching whether the
      crimes were aggravated. Due to this, reports are frequently requested from all
      physicians in all fields of medicine in their daily clinical practices by
      judicial authorities. Following implementation of the new Turkish Penal Code, the
      concept of mental health deterioration was frequently discussed and is still a
      discussed topic in the fields of both law and medicine in terms of crimes against
      sexual immunity. It is believed that subjects discussed in this article will
      provide important information for both adult, child and adolescent mental health
      professionals in terms of drawing attention to the importance of the medicolegal
      evaluations which are frequently requested from psychiatrists in their daily
      clinical practice and in terms of providing an evaluation of the concept of
      mental health deterioration in light of judicial decisions. Regarding the process
      from the beginning of application to the present, prejudications reduce questions
      about how the concept must be evaluated and what the meaning of the concept is.
      In this study, the decisions of Higher Judicial Bodies were researched and
      situations relating to how concepts must be evaluated and the meaning of the
      concept of mental health deterioration today in accordance with the
      prejudications were presented. 

PMID- 24936761
TI  - [Idiopathic bilateral basal ganglia calcification (Fahr's disease) presenting
      with psychotic depression and criminal violence: a case report with forensic
      aspect].
AB  - Fahr's disease is a rare neuropsychiatric disease characterized by bilateral
      intracranial calcification, primarily in the basal ganglia. The more general
      term, Fahr's syndrome, is used for primary and secondary basal ganglia
      calcification, regardless of the etiology, but the term Fahr's disease is used to
      describe primary, idiopathic cases. Fahr's disease may present with neurological
      symptoms, such as parkinsonism and extrapyramidal symptoms, dysarthria, paresis,
      convulsion, and syncope. Psychiatric disorders, including behavioral disorders,
      psychosis, and mood disorders, as well as cognitive disorders can occur. CT is
      useful for the diagnosis of Fahr's disease. Herein we present a patient diagnosed
      as Fahr's disease that presented with symptoms of depression, delusions, and
      auditory hallucinations. The 47-year-old male patient was hospitalized in a
      forensic psychiatry inpatient clinic due to aggressive behavior and was
      subsequently diagnosed with major depressive disorder with psychotic features.
      While hospitalized he was treated with antidepressant and antipsychotic drugs, as
      well as electroconvulsive therapy, resulting in significant improvement in his
      symptoms. As bilateral basal ganglia calcification was observed via CT, the
      patient was diagnosed as Fahr's disease. This case report emphasizes the
      importance of cranial imaging and detailed laboratory examination when evaluating
      patients with psychosis and affective symptoms. Pathologies such as Fahr's
      disease must be included in the differential diagnosis, especially in cases with
      neurological symptoms and cranial imaging findings. 

PMID- 24936762
TI  - Genome-wide analysis of Sphingomonas wittichii RW1 behaviour during inoculation
      and growth in contaminated sand.
AB  - The efficacy of inoculation of single pure bacterial cultures into complex
      microbiomes, for example, in order to achieve increased pollutant degradation
      rates in contaminated material (that is, bioaugmentation), has been frustrated by
      insufficient knowledge on the behaviour of the inoculated bacteria under the
      specific abiotic and biotic boundary conditions. Here we present a comprehensive
      analysis of genome-wide gene expression of the bacterium Sphingomonas wittichii
      RW1 in contaminated non-sterile sand, compared with regular suspended batch
      growth in liquid culture. RW1 is a well-known bacterium capable of mineralizing
      dibenzodioxins and dibenzofurans. We tested the reactions of the cells both
      during the immediate transition phase from liquid culture to sand with or without
      dibenzofuran, as well as during growth and stationary phase in sand. Cells during
      transition show stationary phase characteristics, evidence for stress and for
      nutrient scavenging, and adjust their primary metabolism if they were not
      precultured on the same contaminant as found in the soil. Cells growing and
      surviving in sand degrade dibenzofuran but display a very different transcriptome
      signature as in liquid or in liquid culture exposed to chemicals inducing drought
      stress, and we obtain evidence for numerous 'soil-specific' expressed genes.
      Studies focusing on inoculation efficacy should test behaviour under conditions
      as closely as possible mimicking the intended microbiome conditions. 

PMID- 24936763
TI  - Quorum sensing enhancement of the stress response promotes resistance to quorum
      quenching and prevents social cheating.
AB  - Quorum sensing (QS) coordinates the expression of virulence factors and allows
      bacteria to counteract the immune response, partly by increasing their tolerance
      to the oxidative stress generated by immune cells. Despite the recognized role of
      QS in enhancing the oxidative stress response, the consequences of this
      relationship for the bacterial ecology remain unexplored. Here we demonstrate
      that QS increases resistance also to osmotic, thermal and heavy metal stress.
      Furthermore a QS-deficient lasR rhlR mutant is unable to exert a robust response
      against H2O2 as it has less induction of catalase and NADPH-producing
      dehydrogenases. Phenotypic microarrays revealed that the mutant is very sensitive
      to several toxic compounds. As the anti-oxidative enzymes are private goods not
      shared by the population, only the individuals that produce them benefit from
      their action. Based on this premise, we show that in mixed populations of wild
      type and the mexR mutant (resistant to the QS inhibitor furanone C-30), treatment
      with C-30 and H2O2 increases the proportion of mexR mutants; hence, oxidative
      stress selects resistance to QS compounds. In addition, oxidative stress alone
      strongly selects for strains with active QS systems that are able to exert a
      robust anti oxidative response and thereby decreases the proportion of QS
      cheaters in cultures that are otherwise prone to invasion by cheats. As in
      natural environments stress is omnipresent, it is likely that this QS enhancement
      of stress tolerance allows cells to counteract QS inhibition and invasions by
      social cheaters, therefore having a broad impact in bacterial ecology. 

PMID- 24936764
TI  - Modulation of gut microbiota during probiotic-mediated attenuation of metabolic
      syndrome in high fat diet-fed mice.
AB  - Structural disruption of gut microbiota and associated inflammation are
      considered important etiological factors in high fat diet (HFD)-induced metabolic
      syndrome (MS). Three candidate probiotic strains, Lactobacillus paracasei CNCM I
      4270 (LC), L. rhamnosus I-3690 (LR) and Bifidobacterium animalis subsp. lactis I
      2494 (BA), were individually administered to HFD-fed mice (10(8) cells day(-1))
      for 12 weeks. Each strain attenuated weight gain and macrophage infiltration into
      epididymal adipose tissue and markedly improved glucose-insulin homeostasis and
      hepatic steatosis. Weighted UniFrac principal coordinate analysis based on 454
      pyrosequencing of fecal bacterial 16S rRNA genes showed that the probiotic
      strains shifted the overall structure of the HFD-disrupted gut microbiota toward
      that of lean mice fed a normal (chow) diet. Redundancy analysis revealed that
      abundances of 83 operational taxonomic units (OTUs) were altered by probiotics.
      Forty-nine altered OTUs were significantly correlated with one or more host MS
      parameters and were designated 'functionally relevant phylotypes'. Thirteen of
      the 15 functionally relevant OTUs that were negatively correlated with MS
      phenotypes were promoted, and 26 of the 34 functionally relevant OTUs that were
      positively correlated with MS were reduced by at least one of the probiotics, but
      each strain changed a distinct set of functionally relevant OTUs. LC and LR
      increased cecal acetate but did not affect circulating lipopolysaccharide-binding
      protein; in contrast, BA did not increase acetate but significantly decreased
      adipose and hepatic tumor necrosis factor-alpha gene expression. These results
      suggest that Lactobacillus and Bifidobacterium differentially attenuate obesity
      comorbidities in part through strain-specific impacts on MS-associated phylotypes
      of gut microbiota in mice. 

PMID- 24936767
TI  - Long-term macrolide antibiotic therapy may prevent the development of pneumonia
      in the elderly.

PMID- 24936765
TI  - A single genus in the gut microbiome reflects host preference and specificity.
AB  - Delineating differences in gut microbiomes of human and animal hosts contributes
      towards understanding human health and enables new strategies for detecting
      reservoirs of waterborne human pathogens. We focused upon Blautia, a single
      microbial genus that is important for nutrient assimilation as preliminary work
      suggested host-related patterns within members of this genus. In our dataset of
      57 M sequence reads of the V6 region of the 16S ribosomal RNA gene in samples
      collected from seven host species, we identified 200 high-resolution taxonomic
      units within Blautia using oligotyping. Our analysis revealed 13 host-specific
      oligotypes that occurred exclusively in fecal samples of humans (three
      oligotypes), swine (six oligotypes), cows (one oligotype), deer (one oligotype),
      or chickens (two oligotypes). We identified an additional 171 oligotypes that
      exhibited differential abundance patterns among all the host species. Blautia
      oligotypes in the human population obtained from sewage and fecal samples
      displayed remarkable continuity. Oligotypes from only 10 Brazilian human fecal
      samples collected from individuals in a rural village encompassed 97% of all
      Blautia oligotypes found in a Brazilian sewage sample from a city of three
      million people. Further, 75% of the oligotypes in Brazilian human fecal samples
      matched those in US sewage samples, implying that a universal set of Blautia
      strains may be shared among culturally and geographically distinct human
      populations. Such strains can serve as universal markers to assess human fecal
      contamination in environmental samples. Our results indicate that host
      specificity and host-preference patterns of organisms within this genus are
      driven by host physiology more than dietary habits. 

PMID- 24936766
TI  - High prevalence of biofilm synergy among bacterial soil isolates in cocultures
      indicates bacterial interspecific cooperation.
AB  - Biofilms that form on roots, litter and soil particles typically contain multiple
      bacterial species. Currently, little is known about multispecies biofilm
      interactions and few studies have been based on environmental isolates. Here, the
      prevalence of synergistic effects in biofilm formation among seven different soil
      isolates, cocultured in combinations of four species, was investigated. We
      observed greater biofilm biomass production in 63% of the four-species culture
      combinations tested than in biofilm formed by single-species cultures,
      demonstrating a high prevalence of synergism in multispecies biofilm formation.
      One four-species consortium, composed of Stenotrophomonas rhizophila, Xanthomonas
      retroflexus, Microbacterium oxydans and Paenibacillus amylolyticus, exhibited
      strong synergy in biofilm formation and was selected for further study. Of the
      four strains, X. retroflexus was the only one capable of forming abundant biofilm
      in isolation, under the in vitro conditions investigated. In accordance, strain
      specific quantitative PCR revealed that X. retroflexus was predominant within the
      four-species consortium (>97% of total biofilm cell number). Despite low relative
      abundance of all the remaining strains, all were indispensable for the strong
      synergistic effect to occur within the four-species biofilm. Moreover, absolute
      individual strain cell numbers were significantly enhanced when compared with
      those of single-species biofilms, indicating that all the individual strains
      benefit from inclusion in the multispecies community. Our results show a high
      prevalence of synergy in biofilm formation in multispecies consortia isolated
      from a natural bacterial habitat and suggest that interspecific cooperation
      occurs. 

PMID- 24936768
TI  - Citrullus colocynthis (L.) Schrad (bitter apple fruit): a review of its
      phytochemistry, pharmacology, traditional uses and nutritional potential.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus colocynthis (L.) Schrad is a valuable
      cucurbit plant, widely distributed in the desert areas of the world. Citrullus
      colocynthis fruits are usually recognized for its wide range of medicinal uses as
      well as pharmaceutical and nutraceutical potential. This review aims to appraise
      the published information on the ethnobotanical knowledge, phytochemistry,
      ethnopharmacology, nutraceutical potential and safety studies of Citrullus
      colocynthis (bitter apple) fruit, with critical analysis on the gaps and
      potential for future studies. MATERIAL AND METHODS: A literature survey was
      performed by searching the scientific databases including PubMed, Scopus,
      SciFinder, Google Scholar, Web of Science, ACS as well as published books.
      RESULTS: The plant has been reported to possess a wide range of traditional
      medicinal uses including in diabetes, leprosy, common cold, cough, asthma,
      bronchitis, jaundice, joint pain, cancer, toothache, wound, mastitis, and in
      gastrointestinal disorders such as indigestion, constipation, dysentery,
      gastroenteritis, colic pain and different microbial infections. Several bioactive
      chemical constituents from fruits were recorded, such as, glycosides, flavonoids,
      alkaloids, fatty acids and essential oils. The isolation and identification of
      curcurbitacins A, B, C, D, E, I, J, K, and L and Colocynthosides A, and B were
      also reported. The fruit of Citrullus colocynthis has been studied extensively
      for its wide range of biological activities, which include antioxidant,
      cytotoxic, antidiabetic, antilipidemic, insecticide, antimicrobial and anti
      inflammatory. The plant was also shown to be rich in nutritional value with high
      protein contents and important minerals as well as edible quality of seed oil.
      CONCLUSION: It is evident from the literature that Citrullus colocynthis
      possesses a wide range of medicinal uses and has been well studied for its
      antidiabetic, anticancer, antioxidant, antimicrobial and anti-inflammatory
      activities, while its therapeutic potential for gut, airways and cardiovascular
      disorders remains to be explored. Critical analysis revealed that the plant has
      the huge potential for pharmaceutical and nutraceutical application, with some
      indications for the presence of synergistic and /or side effects neutralizing
      combinations of activities.

PMID- 24936769
TI  - Multi-wavelength photoacoustic imaging of inducible tyrosinase reporter gene
      expression in xenograft tumors.
AB  - Photoacoustic imaging is an emerging hybrid imaging technology capable of
      breaking through resolution limits of pure optical imaging technologies imposed
      by optical-scattering to provide fine-resolution optical contrast information in
      deep tissues. We demonstrate the ability of multi-wavelength photoacoustic
      imaging to estimate relative gene expression distributions using an inducible
      expression system and co-register images with hemoglobin oxygen saturation
      estimates and micro-ultrasound data. Tyrosinase, the rate-limiting enzyme in
      melanin production, is used as a reporter gene owing to its strong optical
      absorption and enzymatic amplification mechanism. Tetracycline-inducible melanin
      expression is turned on via doxycycline treatment in vivo. Serial multi
      wavelength imaging reveals very low estimated melanin expression in tumors prior
      to doxycycline treatment or in tumors with no tyrosinase gene present, but strong
      signals after melanin induction in tumors tagged with the tyrosinase reporter.
      The combination of new inducible reporters and high-resolution photoacoustic and
      micro-ultrasound technology is poised to bring a new dimension to the study of
      gene expression in vivo. 

PMID- 24936771
TI  - PEGylated recombinant human interferon-omega as a long-acting antiviral agent:
      structure, antiviral activity and pharmacokinetics.
AB  - Recombinant human interferon-omega (rhIFN-omega) exhibits a potent antiviral
      activity. Because of poor pharmacokinetics (PK) of rhIFN-omega, frequent dosing
      of rhIFN-omega is necessitated to achieve the sustained antiviral efficacy.
      PEGylation can efficiently improve the PK of rhIFN-omega while substantially
      decrease its bioactivity. The structure, antiviral activity and PK of the
      PEGylated rhIFN-omega were measured to establish their relationship with
      PEGylation sites, polyethylene glycol (PEG) mass and PEG structure. Accordingly,
      N-terminus and the lysine residues were selected as the PEGylation sites. PEGs
      with Mw of 20kDa and 40kDa were used to investigate the effect of PEG mass.
      Linear and branched PEGs were used to investigate the effect of PEG structure.
      PEGylation decreased the antiviral activity of rhIFN-omega and improved its PK.
      The PEGylation sites determine the bioactivity of the PEGylated rhIFN-omega and
      the conjugated PEG mass determines the PK. N-terminally PEGylated rhIFN-omega
      with 40kDa linear PEG maintains 21.7% of the rhIFN-omega antiviral activity with
      a half-life of 139.6h. Thus, N-terminally PEGylated rhIFN-omega with linear 40kDa
      PEG is a potential antiviral agent for long-acting treatment of the viral
      diseases. 

PMID- 24936772
TI  - The antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine in
      the mouse forced swimming test is mediated by serotonergic and dopaminergic
      systems.
AB  - The aim of the present study was to investigate the role of monoaminergic system
      in the antidepressant-like action of 7-fluoro-1,3-diphenylisoquinoline-1-amine
      (FDPI), a derivative of isoquinoline class, in Swiss mice. The antidepressant
      like effect of FDPI was characterized in the modified forced swimming test (FST)
      and the possible mechanism of action was investigated by using serotonergic,
      dopaminergic and noradrenergic antagonists. Monoamine oxidase (MAO) activity and
      [(3)H]serotonin (5-HT) uptake were determined in prefrontal cortices of mice. The
      results showed that FDPI (1, 10 and 20mg/kg, i.g.) reduced the immobility time
      and increased the swimming time but did not alter climbing time in the modified
      FST. These effects were similar to those of paroxetine (8mg/kg, i.p.), a positive
      control. Pretreatments with p-chlorophenylalanine (100mg/kg, i.p., an inhibitor
      of 5-HT synthesis), WAY100635 (0.1mg/kg, s.c., 5-HT1A antagonist), ondansetron
      (1mg/kg, i.p., a 5-HT3 receptor antagonist), haloperidol (0.2mg/kg, i.p., a non
      selective D2 receptor antagonist) and SCH23390 (0.05mg/kg, s.c., a D1 receptor
      antagonist) were effective to block the antidepressant-like effect of FDPI at a
      dose of 1mg/kg in the FST. Ritanserin (1mg/kg, i.p., a 5-HT2A/2C receptor
      antagonist), sulpiride (50mg/kg, i.p., a D2 and D3 receptor antagonist), prazosin
      (1mg/kg, i.p., an alpha1 receptor antagonist), yohimbine (1mg/kg, i.p., an alpha2
      receptor antagonist) and propranolol (2mg/kg, i.p., a beta receptor antagonist)
      did not modify the effect of FDPI in the FST. FDPI did not change synaptosomal
      [(3)H]5-HT uptake. At doses of 10 and 20mg/kg FDPI inhibited MAO-A and MAO-B
      activities. These results suggest that antidepressant-like effect of FDPI is
      mediated mostly by serotonergic and dopaminergic systems. 

PMID- 24936773
TI  - Anxiolytic effects of diphenyl diselenide on adult zebrafish in a novelty
      paradigm.
AB  - Anxiety-related disorders are frequently observed in the population. Because the
      available pharmacotherapies for anxiety can cause side effects, new anxiolytic
      compounds have been screened using behavioral tasks. For example, diphenyl
      diselenide (PhSe)2, a simple organoselenium compound with neuroprotective
      effects, has demonstrated anxiolytic effects in rodents. However, this compound
      has not yet been tested in a novelty-based paradigm in non-mammalian animal
      models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on
      the behavior of adult zebrafish under novelty-induced stress. The animals were
      pretreated with 0.1, 0.25, 0.5, and 1MUM (PhSe)2 in the aquarium water for 30min.
      The fish were then exposed to a novel tank, and their behavior was quantified
      during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration
      dependent manner. At 0.01 and 0.25MUM, (PhSe)2 did not elicit effects on fish
      behavior. At 0.5MUM, moderate behavioral side effects (e.g., lethargy and short
      episodic immobility) were noted. At the highest concentration tested (1MUM),
      dramatic side effects were observed, such as burst behavior and longer periods of
      immobility. The results were confirmed by spatiotemporal analysis of each group.
      Occupancy plot data showed dispersed homebase formation in the 0.25MUM (PhSe)2
      treated group compared with the control group (treated with 0.04% DMSO).
      Furthermore, animals treated with 0.25MUM (PhSe)2 showed a reduction in latency
      to enter the top and spent more time in the upper area of the tank. These data
      suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of
      anxiety evoked by novelty. 

PMID- 24936774
TI  - Gaining control through frustration: two-fold approach for Liquid Crystal three
      dimensional command layers.
AB  - The alignment of Liquid Crystal (LC) molecules, essential for their applications
      in optical devices such as displays, is usually controlled by functionalizing
      their confining surfaces by either patterning or by specific surfactants that
      induce either parallel or perpendicular molecular arrangement. Inducing a
      bistable alignment, such as in the new zenithal bistable displays, offers new
      opportunities in terms of new functionalities and lower energy consumption but a
      full understanding of such bistable alignment appears still complicated. Here we
      present a simple phenomenological model that includes surface topography and
      chemistry. The predicted orientational transitions and bistable states are in
      excellent agreement with experiments, thus making this a proper tool to design
      multistable 3D command layers. 

PMID- 24936777
TI  - Management of mastoid and related disorders.

PMID- 24936776
TI  - Evidence for morphological alterations in prefrontal white matter glia in
      schizophrenia and bipolar disorder.
AB  - BACKGROUND: Brain imaging studies suggest that volume reductions and compromised
      white matter integrity occur in schizophrenia and bipolar disorder (BD). However,
      the cellular correlates have not yet been identified. To address this issue we
      assessed oligodendrocyte, astrocyte and microglial populations in postmortem
      white matter from schizophrenia, BD and nonpsychiatric control samples. METHODS:
      The density, areal fraction and spatial distribution of glial fibrillary acidic
      protein (GFAP)-expressing astrocytes and ionized calcium-binding adaptor molecule
      1 (IBA-1)-expressing microglia as well as the density, nuclear size and spatial
      distribution of Nissl-stained oligodendrocytes were quantified in postmortem
      white matter adjacent to the dorsolateral prefrontal cortex (Brodmann area 9) in
      schizophrenia, BD and control samples (n = 20). In addition, the oligodendrocyte
      associated proteins myelin basic protein and 2,3-cyclic-nucleotide 3
      phosphodiesterase (CNPase) were quantified in the same samples by enzyme-linked
      immunosorbent assay and immunoblotting. RESULTS: Oligodendrocyte density (p =
      0.012) and CNPase protein levels (p = 0.038) differed between groups, being
      increased in BD compared with control samples. The GFAP area fraction (p = 0.05)
      and astrocyte spatial distribution (p = 0.040) also differed between groups,
      reflecting decreased area fraction and increased cell clustering in both
      schizophrenia and BD samples. LIMITATIONS: Oligodendrocytes were identified using
      morphological criteria. CONCLUSION: This study provides evidence for glial
      pathology in prefrontal white matter in schizophrenia and BD. Changes in
      oligodendrocyte and astrocyte populations in white matter in the major
      psychiatric disorders may reflect disruptions in structural or metabolic support
      of axons.

PMID- 24936778
TI  - Chronic otitis media with cholesteatoma with canal fistula and bone conduction
      threshold after tympanoplasty with mastoidectomy.
AB  - OBJECTIVE: To understand the third mobile window effect of chronic otitis media
      with cholesteatoma with inner ear fistula on the bone conduction threshold, we
      examined changes in the bone conduction audiogram after tympanoplasty with
      mastoidectomy for chronic otitis media with cholesteatoma with canal fistula.
      STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center.
      PATIENTS: According to the intraoperative classification of Dornhoffer and
      Milewski, we focused especially on Type IIa (anatomic bony fistula with no
      perilymph leak). We checked the bone conduction threshold at least 3 times: just
      before, just after, and 6 months after surgery in 20 ears with Type IIa lateral
      semicircular canal fistula. INTERVENTION: Tympanoplasty with mastoidectomy. MAIN
      OUTCOME MEASURE: Bone conduction thresholds before and after tympanoplasty with
      mastoidectomy. RESULTS: Compared with the preoperative bone conduction threshold,
      6 cases were better, 12 cases were unchanged, and 2 cases were worse within the
      first postoperative week. Finally, 1 case was better, 15 cases were unchanged,
      and 4 cases were worse at the sixth postoperative month. Patients with a better
      bone conduction threshold in the low-tone frequencies immediately after surgery
      had a tendency to show no preoperative fistula symptoms. Postoperative
      spontaneous nystagmus had a tendency to be observed in patients with a worse bone
      conduction threshold in the high-tone frequencies. CONCLUSION: The better bone
      conduction threshold at low-tone frequencies immediately after tympanoplasty with
      mastoidectomy and no preoperative fistula symptoms might imply the third mobile
      window theory. The worse bone conduction threshold in high-tone frequencies with
      spontaneous nystagmus after surgery might indicate inner ear damage.

PMID- 24936775
TI  - Investigation of the involvement of MIR185 and its target genes in the
      development of schizophrenia.
AB  - BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder of unclear
      etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion.
      Research has yet to confirm which genes within the deletion region are implicated
      in schizophrenia. The minimal 1.5 megabase deletion contains MIR185, which
      encodes microRNA 185. METHODS: We determined miR-185 expression in embryonic and
      adult mouse brains. Common and rare variants at this locus were then investigated
      using a human genetics approach. First, we performed gene-based analyses for
      MIR185 common variants and target genes using Psychiatric Genomics Consortium
      genome-wide association data. Second, MIR185 was resequenced in German patients
      (n = 1000) and controls (n = 500). We followed up promising variants by
      genotyping an additional European sample (patients, n = 3598; controls, n =
      4082). RESULTS: In situ hybridization in mice revealed miR-185 expression in
      brain regions implicated in schizophrenia. Gene-based tests revealed association
      between common variants in 3 MIR185 target genes (ATAT1, SH3PXD2A, NTRK3) and
      schizophrenia. Further analyses in mice revealed overlapping expression patterns
      for these target genes and miR-185. Resequencing identified 2 rare patient
      specific novel variants flanking MIR185. However, follow-up genotyping provided
      no further evidence of their involvement in schizophrenia. LIMITATIONS: Power to
      detect rare variant associations was limited. CONCLUSION: Human genetic analyses
      generated no evidence of the involvement of MIR185 in schizophrenia. However, the
      expression patterns of miR-185 and its target genes in mice, and the genetic
      association results for the 3 target genes, suggest that further research into
      the involvement of miR-185 and its downstream pathways in schizophrenia is
      warranted.

PMID- 24936779
TI  - Neuregulin-3 regulates epithelial progenitor cell positioning and specifies
      mammary phenotype.
AB  - Mutation of Neuregulin-3 (Nrg3) results in defective embryonic mammary gland
      development. Here, we investigate functions of Nrg3 signaling in embryonic
      mammary morphogenesis. Nrg3 regulates the distribution of epithelial progenitor
      cells within the presumptive mammary-forming region during early mammary
      morphogenesis. Basal and suprabasal epithelial cells are significantly smaller
      within the hypoplastic mammary primordium (MP) that forms in Nrg3 mutants,
      indicative of failure to acquire mammary epithelial cell (MEC) morphological
      phenotype. Activation of Erbb4 JM-a CYT-1, an Erbb4 isoform expressed in the
      developing MP, leads to MEC spreading and migration. Nrg3 promotes the
      accumulation of epithelial progenitor cells at the MP site in embryo explant
      cultures. Our results implicate Nrg3 signaling in mediating key events of mammary
      mesenchyme specification, including mesenchymal condensation, mitosis, and
      induction of mammary marker expression. Taken together, our results show Nrg3 has
      a major role in conferring specification of the mammary phenotype to both
      epithelial and mesenchymal progenitor cells. 

PMID- 24936780
TI  - Nutritional recommendations for divers.
AB  - Competitive diving involves grace, power, balance, and flexibility, which all
      require satisfying daily energy and nutrient needs. Divers are short, well
      muscled, and lean, giving them a distinct biomechanical advantage. Although
      little diving-specific nutrition research on performance and health outcomes
      exists, there is concern that divers are excessively focused on body weight and
      composition, which may result in reduced dietary intake to achieve desired
      physique goals. This will result in low energy availability, which may have a
      negative impact on their power-to-weight ratio and health risks. Evidence is
      increasing that restrictive dietary practices leading to low energy availability
      also result in micronutrient deficiencies, premature fatigue, frequent injuries,
      and poor athletic performance. On the basis of daily training demands, estimated
      energy requirements for male and female divers are 3,500 kcal and 2,650 kcal,
      respectively. Divers should consume a diet that provides 3-8 g/kg/day of
      carbohydrate, with the higher values accommodating growth and development. Total
      daily protein intake (1.2-1.7 g/kg) should be spread evenly throughout the day in
      20 to 30 g amounts and timed appropriately after training sessions. Divers should
      consume nutrient-dense foods and fluids and, with medical supervision, certain
      dietary supplements (i.e., calcium and iron) may be advisable. Although sweat
      loss during indoor training is relatively low, divers should follow appropriate
      fluid-intake strategies to accommodate anticipated sweat losses in hot and humid
      outdoor settings. A multidisciplinary sports medicine team should be integral to
      the daily training environment, and suitable foods and fluids should be made
      available during prolonged practices and competitions. 

PMID- 24936781
TI  - Revealing the structure-property relationship of covalent organic frameworks for
      CO2 capture from postcombustion gas: a multi-scale computational study.
AB  - With the aid of multi-scale computational methods, a diverse set of 46 covalent
      organic frameworks (COFs), covering the most typical COFs synthesized to date,
      were collected to study the structure-property relationship of COFs for CO2
      capture. For this purpose, CO2 capture from postcombustion gas (CO2-N2 mixture)
      under industrial vacuum swing adsorption (VSA) conditions was considered as an
      example. This work shows that adsorption selectivity, CO2 working capacity and
      the sorbent selection parameter of COFs all exhibit strong correlation with the
      difference in the adsorbility of adsorbates (DeltaAD), highlighting that
      realization of large DeltaAD can be regarded as an important starting point for
      designing COFs with improved separation performance. Furthermore, it was revealed
      that the separation performance of 2D-layered COFs can be greatly enhanced by
      generating "splint effects", which can be achieved through structural realignment
      to form slit-like pores with suitable size in the structures. Such "splint
      effects" in 2D-COFs can find their similar counterpart of "catenation effects" in
      3D-COFs or MOFs. On the basis of these observations, a new design strategy was
      proposed to strengthen the separation performance of COFs. It could be expected
      that the information obtained in this work not only will enrich the knowledge of
      the structure-property relationship of COFs for separation, but also will largely
      facilitate their future applications to the fields related to energy and
      environmental science, such as natural gas purification, CO2, NO(x) and SO(x)
      capture, etc.

PMID- 24936783
TI  - Toll-like receptors expressed by synovial fibroblasts perpetuate Th1 and th17
      cell responses in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      synovial fibroblast hyperplasia and bone and cartilage erosion. Synovial
      fibroblast- and T cell-mediated inflammation plays crucial roles in the
      pathogenesis of RA. However how this inflammation is initiated, propagated, and
      maintained remains controversial. Here, we systemically examined the contribution
      of toll-like receptors (TLRs) to the inflammatory mediator production as well as
      Th1 and Th17 cell hyperactivity in RA. Our results show that rheumatoid arthritis
      synovial fibroblasts (RASF) express a series of TLRs, including TLR2, TLR3, TLR4,
      and TLR9, with the predominant expression of TLR3. Moreover, the expression
      levels of these TLRs were higher than those in osteoarthritis synovial
      fibroblasts (OASF). Ligation of TLR3, as well as TLR2 and TLR4, resulted in
      vigorous production of inflammatory cytokines, matrix metalloproteinases (MMPs),
      and vascular endothelial growth factor (VEGF) in RASF, with activation of the NF
      kappaB, MAPK, and IRF3 pathways. More important, activation of these TLRs
      expressed by RASF exacerbated inflammatory Th1 and Th17 cell expansion both in
      cell-cell contact-dependent and inflammatory cytokine-dependent manners, which
      induced more IFN-gamma and IL-17 accumulation. Targeting TLRs may modulate the
      inflammation in RA and provide new therapeutic strategies for overcoming this
      persistent disease. 

PMID- 24936784
TI  - Pre- and post-operative nomograms to predict recurrence-free probability in
      korean men with clinically localized prostate cancer.
AB  - OBJECTIVES: Although the incidence of prostate cancer (PCa) is rapidly increasing
      in Korea, there are few suitable prediction models for disease recurrence after
      radical prostatectomy (RP). We established pre- and post-operative nomograms
      estimating biochemical recurrence (BCR)-free probability after RP in Korean men
      with clinically localized PCa. PATIENTS AND METHODS: Our sampling frame included
      3,034 consecutive men with clinically localized PCa who underwent RP at our
      tertiary centers from June 2004 through July 2011. After inappropriate data
      exclusion, we evaluated 2,867 patients for the development of nomograms. The Cox
      proportional hazards regression model was used to develop pre- and post-operative
      nomograms that predict BCR-free probability. Finally, we resampled from our study
      cohort 200 times to determine the accuracy of our nomograms on internal
      validation, which were designated with concordance index (c-index) and further
      represented by calibration plots. RESULTS: Over a median of 47 months of follow
      up, the estimated BCR-free rate was 87.8% (1 year), 83.8% (2 year), and 72.5% (5
      year). In the pre-operative model, Prostate-Specific Antigen (PSA), the
      proportion of positive biopsy cores, clinical T3a and biopsy Gleason score (GS)
      were independent predictive factors for BCR, while all relevant predictive
      factors (PSA, extra-prostatic extension, seminal vesicle invasion, lymph node
      metastasis, surgical margin, and pathologic GS) were associated with BCR in the
      post-operative model. The c-index representing predictive accuracy was 0.792 (pre
      ) and 0.821 (post-operative), showing good fit in the calibration plots.
      CONCLUSIONS: In summary, we developed pre- and post-operative nomograms
      predicting BCR-free probability after RP in a large Korean cohort with clinically
      localized PCa. These nomograms will be provided as the mobile application-based
      SNUH Prostate Cancer Calculator. Our nomograms can determine patients at high
      risk of disease recurrence after RP who will benefit from adjuvant therapy.

PMID- 24936785
TI  - Post-training scopolamine treatment induced maladaptive behavior in open field
      habituation task in rats.
AB  - The effects of scopolamine on memory consolidation are controversial and depend
      on several factors (i.e. site of administration, time of administration and
      testing, dose, cognitive task, experimental protocol, specie, strain, etc.).
      Generally, the range dose of systemic administered scopolamine, used in memory
      consolidation studies, has varied from 0.05 to 50 mg/kg. However, according to
      the literature, the most frequently used doses of scopolamine efficient on memory
      consolidation, are 1 and 30 mg/kg, low and high doses, respectively. In open
      field habituation studies only lower doses of scopolamine were used to test
      memory consolidation. Therefore, in the present study we compared the effects of
      low (1 mg/kg) and high (30 mg/kg) scopolamine dose, on the open field habituation
      task, in male Wistar rats. Scopolamine was administered immediately after the
      acquisition task and animals were retested 48 h later on. On the retested day,
      the ambulation and rearing in the open field decreased in the same manner in all
      tested groups. In saline- and 1 mg/kg scopolamine-treated animals, the time spent
      in grooming significantly decreased in the habituation task, while the same
      parameter significantly increased in animals treated with 30 mg/kg of
      scopolamine. The defecation rate significantly decreased (control group),
      maintained (1 mg/kg of scopolamine treated animals) or significantly increased
      (30 mg/kg of scopolamine treated group) on retention test. In conclusion, the
      present data suggest that post-training scopolamine administration does not
      affect locomotion neither exploration in the habituation to a novel environment,
      but increases defecation and grooming, two behaviours associated with fearful and
      stressful situations. 

PMID- 24936786
TI  - Characterizing the phylogenetic tree community structure of a protected tropical
      rain forest area in Cameroon.
AB  - Tropical rain forests, the richest terrestrial ecosystems in biodiversity on
      Earth are highly threatened by global changes. This paper aims to infer the
      mechanisms governing species tree assemblages by characterizing the phylogenetic
      structure of a tropical rain forest in a protected area of the Congo Basin, the
      Dja Faunal Reserve (Cameroon). We re-analyzed a dataset of 11538 individuals
      belonging to 372 taxa found along nine transects spanning five habitat types. We
      generated a dated phylogenetic tree including all sampled taxa to partition the
      phylogenetic diversity of the nine transects into alpha and beta components at
      the level of the transects and of the habitat types. The variation in
      phylogenetic composition among transects did not deviate from a random pattern at
      the scale of the Dja Faunal Reserve, probably due to a common history and weak
      environmental variation across the park. This lack of phylogenetic structure
      combined with an isolation-by-distance pattern of taxonomic diversity suggests
      that neutral dispersal limitation is a major driver of community assembly in the
      Dja. To assess any lack of sensitivity to the variation in habitat types, we
      restricted the analyses of transects to the terra firme primary forest and found
      results consistent with those of the whole dataset at the level of the transects.
      Additionally to previous analyses, we detected a weak but significant
      phylogenetic turnover among habitat types, suggesting that species sort in
      varying environments, even though it is not predominating on the overall
      phylogenetic structure. Finer analyses of clades indicated a signal of clustering
      for species from the Annonaceae family, while species from the Apocynaceae family
      indicated overdispersion. These results can contribute to the conservation of the
      park by improving our understanding of the processes dictating community assembly
      in these hyperdiverse but threatened regions of the world. 

PMID- 24936787
TI  - Inflammation induces irreversible biophysical changes in isolated nucleus
      pulposus cells.
AB  - Intervertebral disc degeneration is accompanied by elevated levels of
      inflammatory cytokines that have been implicated in disease etiology and matrix
      degradation. While the effects of inflammatory stimulation on disc cell
      metabolism have been well-studied, their effects on cell biophysical properties
      have not been investigated. The hypothesis of this study is that inflammatory
      stimulation alters the biomechanical properties of isolated disc cells and volume
      responses to step osmotic loading. Cells from the nucleus pulposus (NP) of bovine
      discs were isolated and treated with either lipopolysaccharide (LPS), an
      inflammatory ligand, or with the recombinant cytokine TNF-alpha for 24 hours. We
      measured cellular volume regulation responses to osmotic loading either
      immediately after stimulation or after a 1 week recovery period from the
      inflammatory stimuli. Cells from each group were tested under step osmotic
      loading and the transient volume-response was captured via time-lapse microscopy.
      Volume-responses were analyzed using mixture theory framework to investigate two
      biomechanical properties of the cell, the intracellular water content and the
      hydraulic permeability. Intracellular water content did not vary between
      treatment groups, but hydraulic permeability increased significantly with
      inflammatory treatment. In the 1 week recovery group, hydraulic permeability
      remained elevated relative to the untreated recovery control. Cell radius was
      also significantly increased both after 24 hours of treatment and after 1 week
      recovery. A significant linear correlation was observed between hydraulic
      permeability and cell radius in untreated cells at 24 hours and at 1-week
      recovery, though not in the inflammatory stimulated groups at either time point.
      This loss of correlation between cell size and hydraulic permeability suggests
      that regulation of volume change is disrupted irreversibly due to inflammatory
      stimulation. Inflammatory treated cells exhibited altered F-actin cytoskeleton
      expression relative to untreated cells. We also found a significant decrease in
      the expression of aquaporin-1, the predominant water channel in disc NP cells,
      with inflammatory stimulation. To our knowledge, this is the first study
      providing evidence that inflammatory stimulation directly alters the
      mechanobiology of NP cells. The cellular biophysical changes observed in this
      study are coincident with documented changes in the extracellular matrix induced
      by inflammation, and may be important in disease etiology. 

PMID- 24936788
TI  - Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier
      disruption as measured by microdialysis.
AB  - The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound
      (FUS) in the presence of microbubbles for targeted drug delivery. Previous
      studies have illustrated the pharmacokinetics of drug delivery across the BBB
      after sonication using indirect visualization techniques. In this study, we
      investigated the in vivo extracellular kinetics of boronophenylalanine-fructose
      (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis.
      After simultaneous intravenous administration of BPA and FUS exposure, the boron
      concentration in the treated brains was quantified by inductively coupled plasma
      mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma
      dialysate was 3.6 times greater than without FUS, and the area under the
      concentration-time curve was 2.1 times greater. This study demonstrates that
      intracerebral microdialysis can be used to assess local BBB transport profiles of
      drugs in a sonicated site. Applying microdialysis to the study of metabolism and
      pharmacokinetics is useful for obtaining selective information within a specific
      brain site after FUS-induced BBB disruption. 

PMID- 24936789
TI  - Flying-fox species density--a spatial risk factor for Hendra virus infection in
      horses in eastern Australia.
AB  - Hendra virus causes sporadic but typically fatal infection in horses and humans
      in eastern Australia. Fruit-bats of the genus Pteropus (commonly known as flying
      foxes) are the natural host of the virus, and the putative source of infection in
      horses; infected horses are the source of human infection. Effective treatment is
      lacking in both horses and humans, and notwithstanding the recent availability of
      a vaccine for horses, exposure risk mitigation remains an important infection
      control strategy. This study sought to inform risk mitigation by identifying
      spatial and environmental risk factors for equine infection using multiple
      analytical approaches to investigate the relationship between plausible variables
      and reported Hendra virus infection in horses. Spatial autocorrelation (Global
      Moran's I) showed significant clustering of equine cases at a distance of 40 km,
      a distance consistent with the foraging 'footprint' of a flying-fox roost,
      suggesting the latter as a biologically plausible basis for the clustering. Getis
      Ord Gi* analysis identified multiple equine infection hot spots along the eastern
      Australia coast from far north Queensland to central New South Wales, with the
      largest extending for nearly 300 km from southern Queensland to northern New
      South Wales. Geographically weighted regression (GWR) showed the density of P.
      alecto and P. conspicillatus to have the strongest positive correlation with
      equine case locations, suggesting these species are more likely a source of
      infection of Hendra virus for horses than P. poliocephalus or P. scapulatus. The
      density of horses, climate variables and vegetation variables were not found to
      be a significant risk factors, but the residuals from the GWR suggest that
      additional unidentified risk factors exist at the property level. Further
      investigations and comparisons between case and control properties are needed to
      identify these local risk factors. 

PMID- 24936790
TI  - A stable and reproducible human blood-brain barrier model derived from
      hematopoietic stem cells.
AB  - The human blood brain barrier (BBB) is a selective barrier formed by human brain
      endothelial cells (hBECs), which is important to ensure adequate neuronal
      function and protect the central nervous system (CNS) from disease. The
      development of human in vitro BBB models is thus of utmost importance for drug
      discovery programs related to CNS diseases. Here, we describe a method to
      generate a human BBB model using cord blood-derived hematopoietic stem cells. The
      cells were initially differentiated into ECs followed by the induction of BBB
      properties by co-culture with pericytes. The brain-like endothelial cells (BLECs)
      express tight junctions and transporters typically observed in brain endothelium
      and maintain expression of most in vivo BBB properties for at least 20 days. The
      model is very reproducible since it can be generated from stem cells isolated
      from different donors and in different laboratories, and could be used to predict
      CNS distribution of compounds in human. Finally, we provide evidence that
      Wnt/beta-catenin signaling pathway mediates in part the BBB inductive properties
      of pericytes. 

PMID- 24936791
TI  - A new F131V mutation in Chlamydomonas phytoene desaturase locates a cluster of
      norflurazon resistance mutations near the FAD-binding site in 3D protein models.
AB  - The green alga Chlamydomonas reinhardtii provides a tractable genetic model to
      study herbicide mode of action using forward genetics. The herbicide norflurazon
      inhibits phytoene desaturase, which is required for carotenoid synthesis.
      Locating amino acid substitutions in mutant phytoene desaturases conferring
      norflurazon resistance provides a genetic approach to map the herbicide binding
      site. We isolated a UV-induced mutant able to grow in very high concentrations of
      norflurazon (150 uM). The phytoene desaturase gene in the mutant strain contained
      the first resistance mutation to be localised to the dinucleotide-binding
      Rossmann-likedomain. A highly conserved phenylalanine amino acid at position 131
      of the 564 amino acid precursor protein was changed to a valine in the mutant
      protein. F131, and two other amino acids whose substitution confers norflurazon
      resistance in homologous phytoene desaturase proteins, map to distant regions in
      the primary sequence of the C. reinhardtii protein (V472, L505) but in tertiary
      models these residues cluster together to a region close to the predicted FAD
      binding site. The mutant gene allowed direct 5 uM norflurazon based selection of
      transformants, which were tolerant to other bleaching herbicides including
      fluridone, flurtamone, and diflufenican but were more sensitive to beflubutamid
      than wild type cells. Norflurazon resistance and beflubutamid sensitivity allow
      either positive or negative selection against transformants expressing the mutant
      phytoene desaturase gene. 

PMID- 24936792
TI  - Enzymatic treatment of specimens before DNA extraction directly influences
      molecular detection of infectious agents.
AB  - INTRODUCTION: Biological samples, pharmaceuticals or food contain proteins,
      lipids, polymers, ammoniums and macromolecules that alter the detection of
      infectious agents by DNA amplification techniques (PCR). Moreover the targeted
      DNA has to be released from the complex cell walls and the compact nucleoprotein
      matrixes and cleared from potential inhibitors. The goal of the present work was
      to assess the efficiency of enzymatic pretreatments on infectious agents to make
      DNA available for further extraction and amplification. METHODS: Staphylococcus
      epidermidis, Streptococcus mitis, Propionibacterium acnes, Escherichia coli,
      Pseudomonas aeruginosa, Candida albicans, Aspergillus niger and Fusarium solani
      were mixed with an internal control virus and treated with: 1) proteinase K; 2)
      lyticase and 3) lyticase followed by proteinase K. DNAs was manually extracted
      using the QIAmp DNA Mini kit or the MagNA Pure Compact automate. DNA extraction
      yields and the inhibitors were assessed with a phocid Herpesvirus. Bacterial
      detection was performed using TaqMan real-time PCR and yeasts and filamentous
      Fungi with HRM (real-time PCR followed by high-resolution melting analysis).
      RESULTS: Viral DNA was released, extracted and detected using manual and
      automatic methods without pre enzymatic treatments. Either the manual or the
      automatic DNA extraction systems did not meet the sensitivity expectations if
      enzymatic treatments were not performed before: lyticase for Fungi and Proteinase
      K for Bacteria. The addition of lyticase and proteinase K did not improve
      results. For Fungi the detection after lyticase was higher than for Proteinase K,
      for which melting analysis did not allow fungal specification. DISCUSSION:
      Columns and magnetic beads allowed collecting DNA and separate PCR inhibitors.
      Detection rates cannot be related to DNA-avidity of beads or to elution but to
      the lack of proteolysis.

PMID- 24936793
TI  - Fusion of protein aggregates facilitates asymmetric damage segregation.
AB  - Asymmetric segregation of damaged proteins at cell division generates a cell that
      retains damage and a clean cell that supports population survival. In cells that
      divide asymmetrically, such as Saccharomyces cerevisiae, segregation of damaged
      proteins is achieved by retention and active transport. We have previously shown
      that in the symmetrically dividing Schizosaccharomyces pombe there is a
      transition between symmetric and asymmetric segregation of damaged proteins. Yet
      how this transition and generation of damage-free cells are achieved remained
      unknown. Here, by combining in vivo imaging of Hsp104-associated aggregates, a
      form of damage, with mathematical modeling, we find that fusion of protein
      aggregates facilitates asymmetric segregation. Our model predicts that, after
      stress, the increased number of aggregates fuse into a single large unit, which
      is inherited asymmetrically by one daughter cell, whereas the other one is born
      clean. We experimentally confirmed that fusion increases segregation asymmetry,
      for a range of stresses, and identified Hsp16 as a fusion factor. Our work shows
      that fusion of protein aggregates promotes the formation of damage-free cells.
      Fusion of cellular factors may represent a general mechanism for their asymmetric
      segregation at division.

PMID- 24936794
TI  - Regulation and regulatory role of WNT signaling in potentiating FSH action during
      bovine dominant follicle selection.
AB  - Follicular development occurs in wave like patterns in monotocous species such as
      cattle and humans and is regulated by a complex interaction of gonadotropins with
      local intrafollicular regulatory molecules. To further elucidate potential
      mechanisms controlling dominant follicle selection, granulosa cell RNA harvested
      from F1 (largest) and F2 (second largest) follicles isolated at predeviation (PD)
      and onset of diameter deviation (OD) stages of the first follicular wave was
      subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT
      system components was observed. Hence experiments were performed to test the
      hypothesis that WNT signaling modulates FSH action on granulosa cells during
      follicular waves. Abundance of mRNA for WNT pathway members was evaluated in
      granulosa cells harvested from follicles at emergence (EM), PD, OD and early
      dominance (ED) stages of the first follicular wave. In F1 follicles, abundance of
      CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages
      and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2
      follicle at the ED stage. Bovine granulosa cells were treated in vitro with
      increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH.
      IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and
      reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured
      in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for
      WNT pathway members and known FSH targets determined. FSH treatment increased
      CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on
      CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1
      partially reversed the inhibitory effect of FSH. Results support temporal and
      hormonal regulation and a potential role for WNT signaling in potentiating FSH
      action during dominant follicle selection. 

PMID- 24936795
TI  - CCL25/CCR9 interactions regulate the function of iNKT cells in oxazolone-induced
      colitis in mice.
AB  - BACKGROUND: Natural killer T (NKT) cells share phenotypic and functional
      properties with both conventional natural killer cells and T cells. These cells
      might have an important role in the pathogenesis of ulcerative colitis (UC). The
      interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is
      involved in gut-specific migration of leukocytes and induces regulatory T cells
      (Tregs) to migrate to the intestine in chronic ileitis. METHODOLOGY/FINDINGS: In
      UC patients, NKT receptor CD161, CCL25, and CCR9 expression levels were evaluated
      by qRT-PCR. A murine model of oxazolone-induced colitis was induced in BALB/c
      mice. The mRNA levels of NK1.1, CCL25 and CCR9, and pro-inflammatory cytokines in
      mice were evaluated. The CCR9 expression on Type I or invariant NKT (iNKT) cells,
      and the iNKT cells chemotaxis are observed according to flow cytometry. NKT
      receptor CD161, CCL25 and CCR9 expression levels were significantly increased in
      UC patients. And, the mRNA expression levels of NK1.1, CCL25 and CCR9 were
      increased in oxazolone-induced colitis in mice. The production of pro
      inflammatory cytokines was significantly increased, especially interleukin 4 (IL
      4), IL-10 and IL-13. We observed significantly increased CCR9 expression on iNKT
      cells. Furthermore, we found an increased iNKT population and enhanced chemotaxis
      during oxazolone-induced colitis. CONCLUSIONS/SIGNIFICANCE: Our study suggests
      that CCL25/CCR9 interactions may promote the induction and function of iNKT cells
      during oxazolone-induced colitis. These findings may have important implications
      for UC treatment and suggest a role for CCR9 inhibitors.

PMID- 24936796
TI  - Analysis and comparison of somatic mutations in paired primary and recurrent
      epithelial ovarian cancer samples.
AB  - The TP53 mutations have been proved to be predominated in ovarian cancer in a
      study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics
      of recurrent ovarian cancers following initial treatment have been poorly
      estimated. This study was to investigate the pattern of somatic point mutations
      in matched paired samples of primary and recurrent epithelial ovarian cancers,
      using the OncoMap mutation detection protocol. We have adapted a high-throughput
      genotyping platform to determine the mutation status of a large panel of known
      cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set
      of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched
      paired samples of initially diagnosed and recurrent tumors from 46 epithelial
      ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples,
      with 29.3% of these samples having a single mutation and the remaining 4.3%
      having two or more mutations. Among the 41 genes analyzed, 35 mutations were
      found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53
      (20.7%). TP53 was the most frequently mutated gene, but there was no correlation
      between the presence of mutation in any gene and clinical prognosis. Furthermore,
      somatic mutations did not differ between primary and recurrent ovarian
      carcinomas. Every mutation present in recurrent samples was detected in the
      corresponding primary sample. In conclusion, these OncoMap data of Korean EOC
      samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and
      TP53. No differences in mutational status between primary and recurrent samples
      were detected. To understand the biology of tumor recurrence in epithelial
      ovarian cancer, more studies are necessary, including epigenetic modifications or
      additional mutations in other genes. 

PMID- 24936797
TI  - An integrated approach to the taxonomic identification of prehistoric shell
      ornaments.
AB  - Shell beads appear to have been one of the earliest examples of personal
      adornments. Marine shells identified far from the shore evidence long-distance
      transport and imply networks of exchange and negotiation. However, worked beads
      lose taxonomic clues to identification, and this may be compounded by taphonomic
      alteration. Consequently, the significance of this key early artefact may be
      underestimated. We report the use of bulk amino acid composition of the stable
      intra-crystalline proteins preserved in shell biominerals and the application of
      pattern recognition methods to a large dataset (777 samples) to demonstrate that
      taxonomic identification can be achieved at genus level. Amino acid analyses are
      fast (<2 hours per sample) and micro-destructive (sample size <2 mg). Their
      integration with non-destructive techniques provides a valuable and affordable
      tool, which can be used by archaeologists and museum curators to gain insight
      into early exploitation of natural resources by humans. Here we combine amino
      acid analyses, macro- and microstructural observations (by light microscopy and
      scanning electron microscopy) and Raman spectroscopy to try to identify the raw
      material used for beads discovered at the Early Bronze Age site of Great Cornard
      (UK). Our results show that at least two shell taxa were used and we hypothesise
      that these were sourced locally. 

PMID- 24936798
TI  - A label-free fluorescent probe for Hg2+ and biothiols based on graphene oxide and
      Ru-complex.
AB  - A novel, selective and sensitive switch-on fluorescent sensor for Hg(2+) and
      switch-off fluorescent probe for biothiols was developed by using
      [Ru(bpy)2(pip)](2+) as the signal reporter and graphene oxide (GO) as the
      quencher. Due to the affinity of GO towards single-stranded DNA (ss-DNA) and
      [Ru(bpy)2(pip)](2+), the three components assembled, resulting in fluorescence
      quenching. Upon addition of Hg(2+), a double-stranded DNA (ds-DNA) via T-Hg(2+)-T
      base pairs was formed, and [Ru(bpy)2(pip)](2+) intercalated into the newly formed
      ds-DNA. Then, [Ru(bpy)2(pip)](2+) and ds-DNA were removed from the surface of GO,
      resulting in the restoration of fluorescence. Subsequently, upon addition of
      biothiols, Hg(2+) was released from ds-DNA, due to the higher affinity of Hg(2+)
      to the sulfur atoms of biothiols, which could induce ds-DNA unwinding to form ss
      DNA. Then ss-DNA and [Ru(bpy)2(pip)](2+) were adsorbed on the surface of GO, the
      fluorescence of [Ru(bpy)2(pip)](2+) was quenched again. Therefore, the changes in
      emission intensity of [Ru(bpy)2(pip)](2+) directly correlated to the amount of
      detection target (Hg(2+) or biothiols) in solution. The assay exhibited high
      sensitivity and selectivity, with the limits of detection for Hg(2+), cysteine
      (Cys) and glutathione (GSH) to be 2.34 nM, 6.20 nM and 4.60 nM, respectively.

PMID- 24936799
TI  - Quality of life in Alzheimer disease: a comparison of patients' and caregivers'
      points of view.
AB  - Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected
      by Alzheimer Disease (AD) has not been well established, primarily because of the
      difficulties stemming from the study of patients with cognitive disorders.
      Because no cure is currently available for AD, the optimization of QoL represents
      the best possible outcome attainable in all stages of disease, making QoL
      assessment mandatory. This study identified variables related to patients' QoL
      and examined the agreement between patients' and caregivers' QoL ratings. A total
      of 135 dyads (patient and principal caregiver) were enrolled in the study.
      Patients' QoL evaluations showed a negative relationship with depressive mood and
      a positive relationship with Activities of Daily Living (ADL), whereas
      caregivers' QoL ratings showed a negative relationship with patients' depressive
      mood and behavioral disturbances. Caregivers tended to underestimate patients'
      QoL compared with the patients' own self-evaluations, with patients' dependency
      in performing ADL and behavioral disorders as well as caregivers' burdens and
      depression being the main factors associated with the discrepancy in these
      evaluations. These findings suggest that the use of proxies as a substitute for
      the self-report of QoL data should be treated with caution, always accounting for
      the presence of potential bias. 

PMID- 24936801
TI  - Visible-frequency asymmetric transmission devices incorporating a hyperbolic
      metamaterial.
AB  - Asymmetric electromagnetic transmission has been recently demonstrated using
      Lorentz-reciprocal devices, which exploit a variety of patterned structures of
      linear materials to break spatial inversion symmetry. However, nanofabrication
      challenges have so far precluded the fabrication of passive transmission
      structures with highly asymmetric responses at visible frequencies. Here we show
      that high-contrast asymmetric transmission of visible light can be provided by a
      planar device of wavelength-scale thickness incorporating a pair of nonsymmetric
      subwavelength gratings and a passive hyperbolic metamaterial engineered to
      display a transmission window centred at a lateral spatial frequency
      substantially exceeding the diffraction limit. Fabricated devices designed for
      operation at central wavelengths of 532 and 633 nm, respectively, display
      broadband, efficient asymmetric optical transmission with contrast ratios
      exceeding 14 dB. Owing to its planar configuration, small footprint and passive
      operation, this reciprocal transmission approach holds promise for integration
      within compact optical systems operating at visible frequencies. 

PMID- 24936800
TI  - The role of FADS1/2 polymorphisms on cardiometabolic markers and fatty acid
      profiles in young adults consuming fish oil supplements.
AB  - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3)
      fatty acids (FAs) known to influence cardiometabolic markers of health. Evidence
      suggests that single nucleotide polymorphisms (SNPs) in the fatty acid desaturase
      1 and 2 (FADS1/2) gene cluster may influence an individual's response to n-3 FAs.
      This study examined the impact of a moderate daily dose of EPA and DHA fish oil
      supplements on cardiometabolic markers, FA levels in serum and red blood cells
      (RBC), and whether these endpoints were influenced by SNPs in FADS1/2. Young
      adults consumed fish oil supplements (1.8 g total EPA/DHA per day) for 12 weeks
      followed by an 8-week washout period. Serum and RBC FA profiles were analyzed
      every two weeks by gas chromatography. Two SNPs were genotyped: rs174537 in FADS1
      and rs174576 in FADS2. Participants had significantly reduced levels of blood
      triglycerides (-13%) and glucose (-11%) by week 12; however, these benefits were
      lost during the washout period. EPA and DHA levels increased significantly in
      serum (+250% and +51%, respectively) and RBCs (+132% and +18%, respectively)
      within the first two weeks of supplementation and remained elevated throughout
      the 12-week period. EPA and DHA levels in RBCs only (not serum) remained
      significantly elevated (+37% and +24%, respectively) after the washout period.
      Minor allele carriers for both SNPs experienced greater increases in RBC EPA
      levels during supplementation; suggesting that genetic variation at this locus
      can influence an individual's response to fish oil supplements. 

PMID- 24936802
TI  - Variation in local health department primary care services as a function of
      health center availability.
AB  - OBJECTIVES: We aim to gain a clearer understanding of the effect of colocated
      federally qualified health centers (FQHCs) on the delivery of primary care and
      preventive services by local health departments (LHDs). DESIGN: We collected data
      from the 2010 National Association of County & City Health Officials Profile of
      Local Health Departments, the 2010 Uniform Data System, and the 2011 Area
      Resource File. SETTING: Forty-eight states, excluding Rhode Island and Hawaii.
      PARTICIPANTS: The analytic sample contained data on 2107 LHDs across the country.
      MAIN OUTCOME MEASURES: We modeled 4 measures of primary care activity for each
      LHD: provision of screening for (1) heart disease, (2) diabetes, and (3)
      hypertension, and (4) provision of comprehensive primary care. RESULTS: Local
      health departments in counties with an FQHC grantee have, on average, 32% lower
      odds of providing hypertension screening, but having an FQHC grantee in the
      county does not influence LHDs' primary care provision or screening for heart
      disease or diabetes. However, in an alternate model examining FQHC delivery sites
      per capita, each site is associated with a decrease in the odds of LHDs providing
      primary care (4% lower odds) or screening for heart disease (2% lower odds),
      diabetes, or hypertension (both 1% lower odds). CONCLUSION: Local health
      departments are more involved in disease screening than the provision of primary
      care. However, larger LHDs are more likely to provide both screening and primary
      care. Our current study provides evidence that the availability of an FQHC in the
      same county as an LHD partially explains the variation in LHDs' provision of
      primary care services. Local health departments with colocated FQHCs can focus on
      more traditional public health activities, while LHDs in areas without an FQHC
      may find that ensuring access to care is more challenging, possibly leading LHDs
      to directly provide primary care services.

PMID- 24936803
TI  - Hypothalamic-pituitary-adrenal axis response to oral naltrexone in alcoholics
      during early withdrawal.
AB  - INTRODUCTION: It is thought that naltrexone may play a significant role in the
      regulation of the hypothalamic-pituitary-adrenal (HPA) axis response to stress.
      We investigated the HPA axis response following single-dose oral naltrexone
      administration in the early phase of alcohol withdrawal. METHODS: Cortisol and
      adrenocorticotrophic hormone (ACTH) responses to naltrexone were measured in
      alcohol-dependent males (n=23) and in healthy males (n=20). Blood samples were
      collected for cortisol and ACTH measurements before administering (0 min) 50 mg
      naltrexone at 08.00 in the morning, and at 60, 90, 120 and 180 min after
      administering naltrexone. RESULTS: Naltrexone administration resulted in a
      significant ACTH response in the patients while cortisol and ACTH responses were
      found to be significant in the controls. Cortisol response was not large enough
      to reach significance in the patients. ACTH level changes as a response to
      naltrexone in the patients were lower than that in the controls. DISCUSSION: The
      study revealed blunted cortisol and attenuated ACTH responses to naltrexone in
      early alcohol withdrawal. This study may have shown impairment in adrenal and
      pituitary levels during alcohol withdrawal.

PMID- 24936804
TI  - Continuing weight-loss effect after topiramate discontinuation in obese persons
      with schizophrenia: a pilot open-label study.
AB  - INTRODUCTION: Few studies have investigated the likelihood of weight maintenance
      in obese persons with schizophrenia after their initial successful weight loss.
      This pilot open-label study examined the efficacy of topiramate in weight loss
      and the trajectory of weight changes after topiramate discontinuation. METHODS:
      This study enrolled 10 obese persons with schizophrenia. A 4-month treatment
      phase was started, followed by a 12-month discontinuation phase. Body weight was
      measured as the primary outcome every month. Secondary outcomes included leptin
      levels, fasting glucose, lipid profiles, and insulin resistance index. RESULTS:
      After the 4-month addition of topiramate, participants lost 1.79 kg of their body
      weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32
      kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41
      to -2.24, p<0.001). DISCUSSION: The continuing weight-loss effect after
      topiramate discontinuation might have resulted from topiramate's potential to
      improve leptin functioning. These findings demonstrate that topiramate's weight
      loss effect could not only persist during its administration, but also continue
      to improve after its discontinuation.

PMID- 24936805
TI  - Changes in cognitive function during psychogeriatric treatment in relation to
      benzodiazepine cessation.
AB  - INTRODUCTION: The aim of this study was to investigate cognitive functions after
      admission to a geriatric psychiatric hospital, and to study the short-term
      effects of cessation of benzodiazepine use on cognitive functions. METHODS:
      Details of benzodiazepine use and serum concentration measurements were recorded
      on admission. The Hopkins verbal learning test, the Stroop test, Digit Vigilance
      Test and the Mini Mental Status Examination were performed on admission, and
      after 4 weeks of hospitalization. Test results were compared for the total group
      of patients, as well as for benzodiazepine "continuers" and the "quitters".
      RESULTS: For all patients (n=224), improved performances were observed in 10 out
      of 12 cognitive tests. Significant improvements were seen in 4 out of 12 tests.
      Benzodiazepine "quitters" improved significantly more than the "continuers"
      (p=0.027) only on the Hopkins verbal learning test, delayed recall performance.
      DISCUSSION: Among elderly psychiatric patients, cognitive function improved
      slightly during the 4 weeks of hospital treatment, but only for one of the memory
      tests, the improvement was related to the cessation of benzodiazepine treatment.

PMID- 24936806
TI  - Serum levels of PYY(1-36) peptide in patients with schizophrenia on clozapine
      monotherapy.
AB  - INTRODUCTION: The present study was undertaken to determine if patients with
      schizophrenia on clozapine monotherapy have lower serum levels of peptide YY
      [PYY(1-36)], which is an endogenous inhibitor of food intake, comparing to
      healthy controls. METHODS: Data for 24 patients (mean age 38.8 years) with
      paranoid schizophrenia on clozapine monotherapy and 24 healthy subjects (gender-
      and age-matched; mean age 39.9 years) were analyzed. RESULTS: Fasting serum
      levels of PYY(1-36) were lower in the clozapine group (178.4+/-138.4 vs. 277.4+/
      218.1 pg/mL, p=0.034). In the whole study sample PYY(1-36) levels were lower in
      subjects with body mass index>=25 kg/m(2) (p=0.03) and in subjects with abdominal
      obesity defined using International Diabetes Foundation criteria (p=0.04). There
      were no significant differences for metabolic syndrome, smoking, impaired fasting
      glucose, dyslipidemia, and homeostatic model assessment (HOMA) defined insulin
      resistance. DISCUSSION: RESULTS suggest that weight is asso-ciated with levels of
      PYY. Patients on clozapine had higher body mass index, but not fat mass index or
      body weight, therefore lower levels of PYY(1-36) in patients taking clozapine may
      result from clozapine-induced weight gain and central -obesity.

PMID- 24936807
TI  - Down with cut & paste culture.

PMID- 24936808
TI  - Assuring access to quality antiretroviral medicines: the WHO Prequalification of
      Medicines Program and access to HIV treatment.

PMID- 24936809
TI  - [Road traffic injuries in Mexico: evidences to strengthen the Mexican road safety
      strategy].
AB  - Based on a review of secondary data and the scientific literature and an analysis
      of the ENSANut-2012 database, the current study provides a comprehensive overview
      of the current burden of road traffic injuries (RTI) in Mexico and analyzes the
      country's social response to RTI. The high collision, injury, mortality, and
      disability rates associated with this public health problem represent a high cost
      for Mexican society, especially for families. The paper argues that the Mexican
      response has focused on vehicle occupants while overlooking vulnerable road users
      and has prioritized strategies with limited effectiveness. Although the country's
      existing legislation addresses the main risk factors, enforcement has been
      limited. Finally, the paper makes some recommendations for strengthening the
      Mexican strategy to prevent RTI, such as safe, equitable, healthy, and
      sustainable mobility for all types of road users. Despite some strides in RTI
      prevention, there are still challenges and opportunities to be addressed in the
      future. 

PMID- 24936810
TI  - Assessing construct structural validity of epidemiological measurement tools: a
      seven-step roadmap.
AB  - Guidelines have been proposed for assessing the quality of clinical trials,
      observational studies and validation studies of diagnostic tests. More recently,
      the COSMIN (COnsensus-based Standards for the selection of health Measurement
      INstruments) initiative extended those in regards to epidemiological measurement
      tools in general. Among various facets proposed for assessment is the validity of
      an instrument's dimensional structure (or structural validity). The purpose of
      this article is to extend these guidelines. A seven-step roadmap is proposed to
      examine (1) the hypothesized dimensional structure; (2) strength of component
      indicators regarding loading patterns and measurement errors; (3) measurement
      error correlations; (4) factor-based convergent and discriminant validity of
      scales; (5) item discrimination and intensity vis-a-vis the latent trait
      spectrum; and (6) the properties of raw scores; and (7) factorial invariance. The
      paper also holds that the suggested steps still require debate and are open to
      refinements. 

PMID- 24936811
TI  - Physical activity, psychosocial and perceived environmental factors in
      adolescents from Northeast Brazil.
AB  - The aim of this study was to evaluate the association between levels of physical
      activity, psychosocial and perceived environmental factors in adolescents from
      Northeastern Brazil. A cross-sectional epidemiologic study was conducted with
      2,859 adolescents enrolled in secondary schools (57.8% females; mean = 16.5
      years; SD = 1.2) in the city of Joao Pessoa, Paraiba State, Brazil. The following
      physical activity correlates were measured: attitude, self-efficacy, social
      support from friends and parents, and perceived environmental characteristics.
      Physical activity was measured using a questionnaire. Multivariable ordinal
      logistic regression with proportional odds model analysis showed that the
      following factors are positively related to physical activity levels in
      adolescents: attitude, self-efficacy, as well as social support from parents and
      friends. Physical activity intervention programs should increase self-efficacy
      and social support from parents and friends, as well as a positive attitude
      toward physical activity.

PMID- 24936812
TI  - [Health protection for rural workers: the need to standardize techniques for
      quantifying dermal exposure to pesticides].
AB  - Quantification of dermal exposure to pesticides in rural workers, used in risk
      assessment, can be performed with different techniques such as patches or whole
      body evaluation. However, the wide variety of methods can jeopardize the process
      by producing disparate results, depending on the principles in sample collection.
      A critical review was thus performed on the main techniques for quantifying
      dermal exposure, calling attention to this issue and the need to establish a
      single methodology for quantification of dermal exposure in rural workers. Such
      harmonization of different techniques should help achieve safer and healthier
      working conditions. Techniques that can provide reliable exposure data are an
      essential first step towards avoiding harm to workers' health. 

PMID- 24936813
TI  - Dietary patterns and hypertension: a population-based study with women from
      Southern Brazil.
AB  - This study investigated the association between dietary pattern and hypertension
      using the rank reduced regression (RRR). It was a cross-sectional population
      based study with a representative sample of 1,026 women living in the city of Sao
      Leopoldo, Rio Grande do Sul State, Brazil. In order to identify dietary patterns,
      dietary variables from a dietary frequency questionnaire were used as predictors
      and sodium, potassium and saturated fat consumption were selected as response
      variables. The RRR identified three dietary patterns: Factor 1, Factor 2 and
      Factor 3. The association between hypertension and factors 1, 2 and 3, after
      adjustment for socio-demographic, behavioral and obesity variables, was not
      significant. After stratification by age, the association between hypertension
      and factor 2 was present in 40-60 year-old women (tertile 2 compared to 3 RP =
      0.62, 95%CI: 0.43-0.91; p = 0,05). The new statistical method (RRR), proved to be
      a useful tool for identifying dietary patterns. In this study, healthier dietary
      pattern was directly associated with hypertension in women between 40 and 60
      years of age. 

PMID- 24936814
TI  - [Complaints by private health insurance policy-holders to the Consumer Protection
      Bureau in Argentina, 2000-2008].
AB  - This paper analyzes problems experienced by policy-holders of voluntary private
      health insurance plans in Argentina when insurance companies fail to comply with
      the Consumer Protection Code. The sample consisted of consumer complaints filed
      with the Consumer Protection Bureau and rulings by the Bureau from 2000 to 2008.
      One striking issue was recurrent non-compliance with services included in the
      Mandatory Medical Program and the companies' attempts to blame policy-holders.
      According to the study, the lack of an information system hinders scientific
      studies to adequately address the problem. Thus, a comparison with studies on
      health insurance in other Latin American countries highlighted the importance of
      such research, the relationship to health systems, constraints on use and denial
      of citizens' rights to healthcare, and the increasing judicialization of
      healthcare provision. 

PMID- 24936815
TI  - [Specific 5-year oral cancer survival and associated factors in cancer
      outpatients in the Brazilian Unified National Health System].
AB  - This study aimed to analyze the specific five-year oral cancer survival rate and
      associated factors in Brazil. This was a retrospective cohort study using the
      Oncological Database as the source, with probabilistic-deterministic linkage of
      all the records for authorization of radiotherapy and/or chemotherapy in the
      Unified National Health System from 2000 to 2006, generating a single record for
      each patient. The current study included patients diagnosed with oral cancer from
      2002 to 2003 (except for cancer of lip), and ranging from 19 to 100 years of age
      (N = 6,180). Specific five-year survival was 60%. Decreased specific survival was
      associated with: age > 40 years; stages III or IV; location on the tongue, floor
      of the mouth, or base of the tongue; not performing surgical treatment,
      performing only chemotherapy or radiotherapy and chemotherapy; and residence in
      certain States of Brazil. The results emphasize the need to include assessment of
      regional disparities as a possibility for increasing health interventions and
      improving survival. 

PMID- 24936816
TI  - [Factors affecting young mothers' social and family relations after pregnancy].
AB  - This study aimed to analyze factors affecting social and family relations of
      young mothers in the two-year postpartum period. This was a cross-sectional study
      of 464 young mothers in Teresina, Piaui State, Brazil, who gave birth during the
      first four months of 2006 in six maternity hospitals. Data were collected from
      May to December 2008 after identifying the young women in the maternity hospital
      records. Multivariate analysis used multinomial logistic regression. Married
      young women (including those in common-law marriages) were 80% less likely to
      have negative relations with their partners. Participants 20 to 22 years of age
      related 2.4 times better with their mothers than those 17 to 19 years of age.
      Young women not attending school showed 97% higher odds of negative changes in
      relations with friends, and Catholics were 50% less likely to have worse
      relations with friends following childbirth. Measures are needed to orient
      individuals living with young mothers (especially their partners and mothers)
      concerning the importance of support in this phase of life, particularly
      encouraging them to stay in school. 

PMID- 24936817
TI  - [Overbooking in an outpatient healthcare facility in the Brazilian Unified
      National Health System].
AB  - Management issues like resource optimization, cost cuts, quality gains, and
      improvements in care have become increasingly important and are essential to the
      sustainability of healthcare organizations. This study analyzed the efficiency of
      public outpatient care, where the high rate of patient no-show leads to low use
      of resources, while paradoxically the demand for medical care clearly exceeds the
      supply. A quantitative and descriptive approach analyzed the use of "overbooking"
      to reduce the effects of patient no-show in a public outpatient clinic. Using
      statistical and mathematical methods and based on patient and appointment data
      collected from a survey, an interesting comparison was made between levels of
      overbooking and the respective resource utilization rates and service levels for
      each scenario. The findings point to important gains in efficiency, thus
      demonstrating the potential of increasing the number of services in the same
      asset base. 

PMID- 24936818
TI  - Functional performance and social relations among the elderly in Greater
      Metropolitan Belo Horizonte, Minas Gerais State, Brazil: a population-based
      epidemiological study.
AB  - This study was conducted in a probabilistic sam- ple of 2,055 elderly in Greater
      Metropolitan Belo Horizonte, Minas Gerais State, Brazil, to examine components of
      social network (conjugal status and visits by the children, other relatives, and
      friends) and social support (satisfaction with personal relations and having
      persons on whom to rely) associated with limitations in performing basic
      activities of daily living (ADL). Multivariate analysis used the Hurdle model.
      Performance of ADL showed independent and statistically significant associations
      with social network (fewer meetings with friends and not having children) and
      personal support (dissatisfaction/indifference towards personal relations). These
      associations remained after adjusting for social and demographic characteristics,
      health status, and other indicators of social relations. Our results emphasize
      the need for greater attention to social network and social support for elderly
      with functional limitations and those with weak social networks and social
      support. 

PMID- 24936819
TI  - [Relative validity of dietary indicators from the Brazilian National School-Based
      Health Survey among adolescents in Rio de Janeiro, Brazil].
AB  - This study evaluated the relative validity of the dietary indicators from the
      questionnaire used in the Brazilian National School-Based Health Survey (PeNSE)
      in the city of Rio de Janeiro, Brazil. The sample included 174 students. The
      following indicators were evaluated: regular consumption (>= 5 times a week) of
      markers for healthy eating, markers for unhealthy eating, and routine eating
      habits (having meals with parents or guardians (MEAL), having breakfast
      (breakfast), and eating while studying or watching TV. The results of the
      questionnaire were compared with three 24-hour recalls. For all the markers of
      healthy eating, there was no difference in the proportion of regular consumption
      when comparing the two methods. The rates detected by the questionnaire were
      higher for packaged snacks and crackers and lower for cold cuts and MEAL. The
      indicators for regular consumption of markers for healthy eating and that
      referring to BREAKFAST were those with the highest accuracy. The dietary
      indicators used by the PeNSE survey showed satisfactory validity. 

PMID- 24936820
TI  - [Factors associated with use of medication during first pregnancies in Rio
      Branco, Acre State, Brazil].
AB  - This cross-sectional study in a sample of 887 primigravidae in Rio Branco, Acre
      State, Brazil aimed to analyze factors associated with the use of medicines
      during the first pregnancy. Information was obtained from interviews and prenatal
      cards. Medicines were classified according to the Anatomical Therapeutic Chemical
      (ATC) Classification System of the World Health Organization and risk categories
      according to the U.S. Food and Drug Administration. Mean age was 21 years and
      mean number of medicines used was 2.42. The most frequently consumed medicines
      were antianemics (47.5%), supplements and vitamins (18.7%), analgesics (13.8%),
      and antibiotics (10.5%). In the risk categorization, 69.3% belonged to category
      A, 22.3% to B, 7.6% to C, and 0.8% to D. The odds of having used risky medicines
      were higher among primigravidae in unit B (OR = 2.10; 95%CI: 1.26-3.50), in the
      19 to 24-year age bracket (OR = 2.79; 95%CI: 1.58-4.93), and in the presence of a
      medical prescription (OR = 1.86; 95%CI: 1.18-2.95). Essential drugs were less
      used by women with higher family income (OR = 0.63; 95%CI: 0.42-0.96) and those
      who had received private prenatal care (OR = 0.53; 95%CI: 0.38-0.74). 

PMID- 24936821
TI  - [Suicide and suicide attempts by exogenous poisoning in Rio de Janeiro, Brazil:
      information analysis through probabilistic linkage].
AB  - Poisoning is one of the three main means used in suicide and suicides attempts.
      In order to improve the quality of such information, a cross-sectional
      descriptive study was conducted on case records in the State of Rio de Janeiro,
      Brazil, from 2006 to 2008, in the databases of the Information System on Diseases
      of Notification (SINAN), the Mortality Information System (SIM), and the Poison
      Control Center in Niteroi (CCIn-Niteroi). Probabilistic linkage was used to
      develop a model for monitoring suicides and suicide attempts by poisoning.
      Although 68.8% of the 948 records at CCIn had been reported by health
      professionals, only 2.6% were included in the other databases. Linking CCIn and
      SIM showed 61.3% underreporting. Information is important for surveillance,
      public policy-making, and decision-making. Probabilistic linkage allowed
      identifying problems in each system and provided better data quality and a more
      accurate diagnosis of the real situation in a complex and serious problem like
      suicidal behavior. 

PMID- 24936822
TI  - [Food insecurity in Brazilian families with children under five years of age].
AB  - This article analyzes food insecurity and hunger in Brazilian families with
      children under five years of age. This was a nationally representative cross
      sectional study using data from the National Demographic and Health Survey on
      Women and Children (PNDS-2006), in which the outcome variable was moderate to
      severe food insecurity, measured by the Brazilian Food Insecurity Scale (EBIA).
      Prevalence estimates and prevalence ratios were generated with 95% confidence
      intervals. The results showed a high prevalence of moderate to severe food
      insecurity, concentrated in the North and Northeast regions (30.7%), in economic
      classes D and E (34%), and in beneficiaries of conditional cash transfer programs
      (36.5%). Multivariate analysis showed that the socioeconomic relative risks
      (beneficiaries of conditional cash transfers), regional relative risks (North and
      Northeast regions), and economic relative risks (classes D and E) were 1.8, 2.0
      and 2.4, respectively. Aggregation of the three risks showed 48% of families with
      moderate to severe food insecurity, meaning that adults and children were going
      hungry during the three months preceding the survey. 

PMID- 24936823
TI  - Individual and local level factors and antenatal care use in Colombia: a
      multilevel analysis.
AB  - This paper examined the association between individual and local level factors
      and the number of antenatal care visits completed by women in Colombia using data
      from the 2010 Colombian Demographic and Health Survey and multilevel logistic
      regression models. Our findings suggest that, in addition to maternal
      socioeconomic status, contextual factors influence whether pregnant women
      complete the minimum recommended number of antenatal care visits. These factors
      include: level of women's autonomy in the community, regional inequalities and
      access barriers caused by distance (OR = 0.057), costs of services (OR = 0.035),
      and/or a lack of confidence in doctors (OR = 0.036). Our results highlight the
      existence of inequalities in access to antenatal care and the importance of
      considering the local context in the design of effective maternal care policies
      in Colombia. Furthermore, our findings regarding individual factors corroborate
      the evidence from other countries and offer new insights into the association
      between local level factors and number of antenatal care visits. 

PMID- 24936824
TI  - Average years of life lost due to breast and cervical cancer and the association
      with the marginalization index in Mexico in 2000 and 2010.
AB  - The objective of this study was to calculate average years of life lost due to
      breast and cervical cancer in Mexico in 2000 and 2010. Data on mortality in women
      aged between 20 and 84 years was obtained from the National Institute for
      Statistics and Geography. Age-specific mortality rates and average years of life
      lost, which is an estimate of the number of years that a person would have lived
      if he or she had not died prematurely, were estimated for both diseases. Data was
      disaggregated into five-year age groups and socioeconomic status based on the
      2010 marginalization index obtained from the National Population Council. A
      decrease in average years of life lost due to cervical cancer (37.4%) and an
      increase in average years of life lost due breast cancer (8.9%) was observed
      during the period studied. Average years of life lost due to cervical cancer was
      greater among women living in areas with a high marginalization index, while
      average years of life lost due to breast cancer was greater in women from areas
      with a low marginalization index. 

PMID- 24936825
TI  - [Portuguese-language translation and cross-cultural adaptation of the Fatigue
      domain of Patient-Reported-Outcomes Measurement Information System (PROMIS)].
AB  - The items bank of the Fatigue domain is part of an American system developed for
      evaluation of results reported by patients, called Patient-Reported-Outcomes
      Measurement Information System (PROMIS). This study aimed to translate and cross
      culturally adapt this item bank for the Brazilian population, as a promising new
      tool for evaluating health-related quality of life. The items in this bank were
      translated using rigorous translation and back-translation protocols. The
      translated version was pre-tested in twenty Brazilians with a brief cognitive and
      retrospective interview in order to test the items' conceptual, cultural, and
      semantic equivalences. In the translation and back-translation process, only
      three of the 82 items had to be reworded due to the culturally inadequate
      content. In the pretest, only four items needed to be reworded, but without
      conceptual and semantic alterations. The results showed that the translated
      version of this item bank is conceptually, culturally, and semantically
      equivalent to the original version. 

PMID- 24936826
TI  - [Cross-cultural adaptation of the instrument Appraisal of Guidelines For Research
      & Evaluation II (AGREE II) for assessment of clinical guidelines].
AB  - This article describes the adaptation of the Appraisal of Guidelines for Research
      & Evaluation II (AGREE II) instrument into Portuguese. A cross-cultural
      adaptation followed internationally accepted standards with the stages of
      translation, synthesis, back-translation, evaluation by an expert committee, and
      external evaluation. The translated instrument was published on the official
      AGREE websites. 

PMID- 24936827
TI  - [Prevalence of human papillomavirus (HPV) in Belem, Para State, Brazil, in the
      oral cavity of individuals without clinically diagnosable injuries].
AB  - This cross-sectional study aimed to determine HPV prevalence in the oral cavity
      of individuals without clinically diagnosable lesions and to identify the
      respective HPV types. A total of 166 samples were analyzed from patients 18 years
      or older in the State of Para, Brazil. Samples were collected by sterile brush
      scraping in the oral cavity. HPV detection used polymerase chain reaction (PCR).
      Infected samples were typed as HPV 6, 11, 16, 18, 31, 33, 35, 52, and 58. HPV was
      present in 40 samples (24.1%). Three samples (7.5%) were positive for HPV 6, five
      (12.5%) for HPV 18, and one (2.5%) for HPV 58. 

PMID- 24936828
TI  - [Letter to the Editors regarding the editorial published in volume 30, number 1].

PMID- 24936831
TI  - [The author replies].

PMID- 24936832
TI  - Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by
      combining in vitro fertilization and CRISPR/Cas9 technology.
AB  - Humanized mouse models have become increasingly important and widely used in
      modeling human diseases in biomedical research. Immunodeficient mice such as NOD
      Rag1-/-IL2RgammaC-null (NRG) or NOD-SCID-IL2RgammaC-null (NSG) mice are critical
      for efficient engraftment of human cells or tissues. However, their genetic
      modification remains challenging due to a lack of embryonic stem cells and
      difficulty in the collection of timed embryos after superovulation. Here, we
      report the generation of gene knockout NRG mice by combining in vitro
      fertilization (IVF) and CRISPR/Cas9 technology. Sufficient numbers of fertilized
      embryos were produced through IVF, and a high rate of Fah gene targeting was
      achieved with microinjection of Cas9 mRNA, gRNA and single strand oligonucleotide
      DNA (ssDNA) into the embryos. The technology paves the way to construct NRG or
      NSG mutant mice to facilitate new humanized mouse models. The technology can also
      be readily adapted to introduce mutations in other species such as swine and non
      human primates. 

PMID- 24936833
TI  - An actin-binding protein espin is a growth regulator for melanoma.

PMID- 24936834
TI  - DC-HIL-expressing myelomonocytic cells are critical promoters of melanoma growth.
AB  - A major barrier to successful cancer immunotherapy is the tumor's ability to
      induce T-cell tolerance by exploiting host regulatory mechanisms. Having
      discovered the DC-HIL receptor, which inhibits T-cell responses by binding to
      syndecan-4 on effector T cells, we posited the DC-HIL/syndecan-4 pathway to have
      an important role in cancer promotion. Among DC-HIL(+) myelomonocytic cells,
      during growth of implanted mouse melanoma, CD11b(+)Gr1(+) cells were the most
      expanded population and the most potent at suppressing T-cell activation.
      Deletion of the DC-HIL gene or infusion of anti-DC-HIL mAb abrogated these cells'
      suppressor function and expansion, and markedly diminished melanoma growth and
      metastasis. IL-1beta and IFN-gamma were elevated in mice bearing melanoma, and
      concurrent exposure to both cytokines optimally induced DC-HIL expression by
      tumor-infiltrating CD11b(+)Gr1(+) cells. Ligation of DC-HIL transduced
      phosphorylation of its intracellular immunoreceptor tyrosine-based activation
      motif, which in turn induced intracellular expression of IFN-gamma and inducible
      nitric oxide synthase (iNOS), known to mediate T-cell suppression by
      CD11b(+)Gr1(+) cells. Thus, DC-HIL is the critical mediator of these cells'
      suppressor function in melanoma-bearing mice and a potential target for improving
      melanoma immunotherapy. 

PMID- 24936835
TI  - Captopril protects against burn-induced cardiopulmonary injury in rats.
AB  - BACKGROUND: This study was designed to determine the possible protective effect
      of captopril treatment against oxidative damage in heart and lung tissues induced
      by burn injury. METHODS: Under ether anesthesia, the shaved dorsum of Wistar
      albino rats was exposed to 90 degrees C water bath for 10 seconds. Captopril was
      administered intraperitoneally (10 mg/kg) after the burn injury and repeated
      twice daily. In the sham group, the dorsum was dipped in a 25 degrees C water
      bath for 10 seconds. At the end of the 24 hours, echocardiographic recordings
      were performed, then animals were decapitated and heart and lung tissue samples
      were taken for the determination of tumor necrosis factor-alpha (TNF-alpha) as a
      pro-inflammatory cytokine, malondialdehyde and glutathione levels and
      myeloperoxidase, caspase-3, and Na+,K+-ATPase activity in addition to the
      histological analysis. RESULTS: Burn injury caused significant alterations in
      left ventricular function. In heart and lung tissues, TNF-alpha and
      malondialdehyde levels and myeloperoxidase and caspase-3 activities were found to
      be increased, while glutathione levels and Na+, K+-ATPase activity were decreased
      due to burn injury. Captopril treatment significantly elevated the reduced
      glutathione level and Na+, K+-ATPase activity, and decreased cytokine and
      malondialdehyde levels and myeloperoxidase and caspase-3 activities. CONCLUSION:
      Captopril prevents burn-induced damage in heart and lung tissues and protects
      against oxidative organ damage.

PMID- 24936836
TI  - The effect of hyperbaric oxygen therapy on fracture healing in nicotinized rats.
AB  - BACKGROUND: The aim of the present study was to investigate the effect of
      hyperbaric oxygen therapy on fracture healing in nicotinized rats. METHODS:
      Thirty-two rats were divided as follows: nicotinized group (1), hyperbaric oxygen
      group (2), nicotinized + hyperbaric oxygen group (3), and control group (4). For
      28 days, nicotine was administered in Groups 1 and 3. Then, a standard shaft
      fracture was induced in the left femur of rats. Groups 2 and 3 underwent
      hyperbaric oxygen therapy for 21 days. At the end of the experiment, fracture
      site, left femur and whole body bone mineral content and density were measured.
      RESULTS: The radiological and histopathological scores of Group 1 were
      statistically significantly lower compared to Groups 2, 3 and 4, and there was no
      statistically significant difference between the Groups 2, 3 and 4. In a
      comparison between the groups, no statistically significant difference was found
      in terms of bone mineral content and density values measured at the fracture
      site, left femur and whole body. CONCLUSION: The negative effects of nicotine on
      fracture healing are eliminated with hyperbaric oxygen therapy, but hyperbaric
      oxygen alone does not cause significant changes in healing (radiologically and
      histopathologically).

PMID- 24936837
TI  - Effectiveness of hyperbaric oxygen and ozone applications in tissue healing in
      generated soft tissue trauma model in rats: an experimental study.
AB  - BACKGROUND: Soft tissue trauma is a type of acute traumatic ischemia. We
      investigated in this study whether the edema, inflammation and ischemia caused by
      the trauma could be affected positively by hyperbaric oxygen (HBO) and ozone
      therapy. METHODS: Soft tissue trauma was generated in a total of 63 adult male
      Sprague-Dawley rats. Subsequently, rats were divided into three groups. The first
      group was treated with ozone, the second group with HBO, and the third group
      served as controls. Tissue and blood samples were taken at the end of the
      procedures. Tissue lipid peroxidation (LPO), superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), inducible nitric oxide synthase (iNOS), heme
      oxygenase (HO)-1, and hypoxia-inducible factor (HIF)-1 levels were detected.
      Hematoxylin-eosin staining was used to determine the inflammation and edema
      histopathologically. RESULTS: We also detected HIF-1 activity, which decreases
      when the oxygen concentration increases, HO-1 activity, which has anti
      inflammatory effects, and iNOS activity, which releases in any type of acute
      case. We determined a statistically significant reduction in iNOS and LPO levels
      in both the HBO and Ozone groups. A significant decrease in inflammation was
      detected in both the Ozone and HBO groups compared with the Control group, and a
      significant decrease in edema was detected in all three groups. CONCLUSION: We
      think that HBO and Ozone therapy have beneficial effects on biochemical and
      histopathological findings. Related clinical trials will be helpful in clarifying
      the effects.

PMID- 24936838
TI  - Psychiatric disorders and their association with burn-related factors in children
      with burn injury.
AB  - BACKGROUND: The aim of this study was to assess psychiatric disorders and their
      association with burn-related factors in a population of Turkish children with
      burns. METHODS: Thirty-one children admitted to the Cerrahpasa Medical Faculty
      Burn Unit between January 2013 and August 2013 were first assessed by the plastic
      surgeon, and then those with psychological symptoms were referred to a child
      psychiatrist, and the records were analyzed retrospectively. RESULTS: The
      percentage of burned area to Total Body Surface Area (TBSA) ranged between 2-60%
      (mean, 17.3%). Nineteen patients (61.3%) had a psychiatric diagnosis, which
      included acute stress disorder (ASD) (n=15), depression (n=3), posttraumatic
      stress disorder (n=2, comorbid with depression), and delirium (n=1). The
      percentage of burned area to TBSA was associated with the presence of
      psychopathology and ASD. Further, psychopathology was associated with the number
      of burned major body regions. CONCLUSION: Pediatric burn patients are at risk of
      developing psychopathology. The children with a greater percentage of burned area
      to TBSA and more burned body regions have the greatest risk of psychopathology.
      Surgeons have an important role in patient referral for psychiatric
      interventions, so that psychiatric disorders can be prevented as early as
      possible.

PMID- 24936839
TI  - Traumatic wound dehiscence after penetrating keratoplasty.
AB  - BACKGROUND: We aimed to evaluate the risk factors, clinical features and outcomes
      of surgery for traumatic wound dehiscence (TWD) following penetrating
      keratoplasty (PK). METHODS: Twenty-six patients with TWD following PK were
      evaluated retrospectively in terms of factors related to the trauma, types of
      reconstructive surgery, final graft clarity, and visual acuity. RESULTS: There
      were 26 patients with a mean age of 40.7+/-19.6 years. In 12 (46.1%) patients,
      the better eye was affected by the trauma. The most frequent type of trauma was
      blunt trauma by various objects (9). In all cases, the dehiscence was at the
      graft host junction. The mean extent of detachment was 135.4 degrees +/-57.6
      degrees . Crystalline or intraocular lens damage was present in 42.3% of cases.
      Median follow-up time after the reconstructive surgery was 36 months. The graft
      remained clear in 13 (50%) patients, whereas graft insufficiency/graft rejection
      developed in 13 (50%) patients. Final visual acuity was over 20/200 in 13 (50%)
      patients. CONCLUSION: TWD may occur at any time after PK, most frequently within
      the first postoperative year. Low visual acuity in the other eye seems to be a
      major risk factor. In patients without major complications such as posterior
      segment damage, visual outcomes and graft survival can be favorable.

PMID- 24936840
TI  - Comparison of intramedullary nail and plate fixation in distal tibia diaphyseal
      fractures close to the mortise.
AB  - BACKGROUND: In this study, we aimed to compare the functional and radiological
      results of intramedullary nailing and plate fixation techniques in the surgical
      treatment of distal tibia diaphyseal fractures close to the ankle joint. METHODS:
      Between 2005 and 2011, 55 patients (32 males, 23 females; mean age 42 years;
      range 15 to 72 years) who were treated with intramedullary nailing (21 patients)
      or plate fixation (34 patients) due to distal tibia diaphyseal fracture were
      included in the study. The average follow-up period was 27.6 months (range, 12-82
      months). The patients were evaluated with regard to nonunion, malunion,
      infection, and implant irritation. The AOFAS (American Orthopaedic Foot and Ankle
      Society) scale was used for the clinical evaluation. RESULTS: No statistically
      significant difference was found between the two surgical methods with respect to
      unification time, AOFAS score, accompanying fibula fracture, material irritation,
      and malunion. Nine patients had open fractures, and these patients were treated
      with plate fixation (p=0.100). Nonunion developed in three patients who were
      treated with plates. Infection occurred in one patient. Anterior knee pain was
      significantly higher in patients who were treated with intramedullary nails.
      There was no malunion in any patient. CONCLUSION: As the distal fragment is not
      long enough, plate fixation technique is usually preferred in the treatment of
      distal tibia diaphyseal fractures. In this study, we observed that if the
      surgical guidelines are followed carefully, intramedullary nailing is an
      appropriate technique in this kind of fracture. The malunion rates are not
      significantly increased, and it also has the advantages of being a minimally
      invasive surgery with fewer wound problems.

PMID- 24936841
TI  - A new, simple technique for gradual primary closure of fasciotomy wounds.
AB  - BACKGROUND: The aim of this study was to demonstrate a new, easy and safe
      technique, which has not been defined in the literature previously, that enables
      the gradual primary closure of fasciotomy wounds using barbed sutures. METHODS:
      The technique was performed on five patients who presented with fasciotomy wounds
      on both upper and lower extremities, varying in size, observed after compartment
      syndrome due to different causes. The average width of the defects for which
      primary closure was planned was 8.8 cm. Following the fasciotomy incision,
      absorbable barbed sutures were inserted through the dermal tissue around the
      wound similar to that of a subcuticular closure, but left loose, after which
      closed dressing was applied. During the clinical follow-up, with the decrease in
      tissue edema and tightness around the wound, the barbed suture was tightened at
      bedside every 48-72 hours. RESULTS: At the end of this gradual closure, all the
      fasciotomy defects were primarily closed within an average of 8.6 days. All the
      patients had complete and uncomplicated primary closure with the exception of one
      with high-voltage electrical burn injury, who developed necrosis in the distal
      part of the defect, and was treated by secondary healing. CONCLUSION: The gradual
      fasciotomy closure technique with barbed suture seems to be an easy, rapid and
      effective method.

PMID- 24936843
TI  - [Results of arthroscopic repair of triangular fibrocartilage complex peripheral
      tears (Palmer type 1B)].
AB  - BACKGROUND: Triangular fibrocartilage complex (TFCC) injury is the major cause of
      wrist pain on the ulnar side. In this study, treatment outcomes of
      arthroscopically repaired peripheral TFCC tears (Palmer type 1B) were evaluated
      retrospectively. METHODS: Thirty-eight patients (30 males, 8 females; mean age
      27.6; range 19 to 42 years) with TFCC tears (Palmer type 1B) who were treated
      arthroscopically between February 2007-July 2012 were evaluated retrospectively.
      The data were collected by Mayo wrist evaluation form and by preoperative and
      postoperative visual analogue scale (VAS). RESULTS: The results of the data
      collected by the Mayo wrist evaluation forms were perfect in 30 patients and good
      in 8 patients. Preoperative VAS was 6.53 (range: 4.5-8.2) and postoperative VAS
      was 1.48 (range: 0.3-3.1). DISCUSSION: With the arthroscopic technique, TFCC
      tears can be repaired with minimal harm and better visualization, and evaluation
      of all the structures of the wrist can be done. Outside-to-inside suturing
      technique, which is performed through the portal opened 1 cm inferior to the 6R
      portal, is the least traumatic technique and does not carry the risk of injury to
      the superficial branch of the ulnar nerve. With this technique, the complaints of
      preoperative pain can be eliminated significantly.

PMID- 24936842
TI  - [The results of autologous bone graft and titanium headless cannulated
      compression screw for treatment of scaphoid nonunion].
AB  - BACKGROUND: We aimed to present the clinical and radiological results of patients
      treated with debridement, iliac bone graft and titanium headless compression
      screw for scaphoid nonunion. METHODS: We retrospectively evaluated 24 patients
      (23 males, 1 female) who underwent this technique between 2009 and 2012, with a
      minimum of 12 months' follow-up. Nonunion was determined as no union evidence
      within eight weeks on radiological view. Scaphoid fracture was classified
      according to Herbert classification and anatomical location. Functional
      evaluation was performed using the Mayo wrist scoring system. RESULTS: According
      to the Herbert classification system, there were 20 D1 and 4 D2 fractures.
      Anatomical location included 1 distal, 6 proximal and 17 corpus. Fracture union
      was achieved in all but 2 patients, with a mean union time of 9.5 weeks (6-15).
      Scapholunate angle and radiolunate angle were measured as a mean 32 degrees  (39
      degrees -50 degrees ) and 7 degrees  (4 degrees -10 degrees ) at the latest
      follow-up radiographic examination. There was a statistically significant
      correlation between the length of the pseudoarthrosis period and union time
      (p=0.003). Union time of proximal fractures was longer than of the others
      (p=0.004). Mayo wrist score was 86 (80-95). DISCUSSION: Autologous iliac bone
      graft and titanium headless cannulated compression screw combination via volar
      approach is safe and effective for scaphoid nonunion.

PMID- 24936844
TI  - Supraventricular tachycardia due to blunt chest trauma in an adolescent.
AB  - Blunt chest trauma and its associated complications represent a rare cause of
      cardiac arrest in a healthy child, although an increasing number of these events
      have been reported. Victims are most often diagnosed in ventricular fibrillation
      or tachycardia. However, cardiac conduction abnormalities are also reported. In
      this report, a healthy adolescent with supraventricular tachycardia associated
      with blunt chest trauma due to a football is presented. This is the first report
      in the literature of atrial arrhythmia in these cases with chest trauma. 

PMID- 24936845
TI  - Are blank cartridge guns really harmless?
AB  - Blank cartridge guns are devices that discharge sound and gas, but no bullet or
      shot. These devices are very similar to real guns in the form of their external
      design and the sound generated during their firing. Although it is widely held in
      society that these devices are harmless, reports from Turkey and the world have
      shown that these guns are not entirely innocent. Herein, we present a 26-year-old
      male with a head injury due to gunshot from a blank cartridge. The purpose of
      this presentation is to emphasize that these devices are not harmless, contrary
      to common public opinion. 

PMID- 24936846
TI  - Successful emergency department thoracotomy for traumatic cardiac rupture:
      effective utilization of a fret sternum saw.
AB  - Mortality following blunt chest injury and cardiac rupture remains high despite
      advances in the care of traumatic injuries. Indeed, most patients succumb to
      these injuries even prior to reaching a hospital. However, timely recognition and
      surgical intervention can save lives. We present the case of a 40-year-old woman
      who presented to our emergency department in cardiac arrest due to rupture of her
      left atrium following a major motor vehicle collision. The patient underwent
      emergency department thoracotomy with successful repair of the cardiac rupture.
      Emergency department thoracotomy, when indicated and performed by trained
      surgeons, can be the only life-saving procedure available. Rapid median
      sternotomy using a cost-effective fret sternum saw does not require significantly
      more time than a left lateral thoracotomy or clamshell incision in an emergency
      situation. It can be an effective and alternative method of thoracic entry in the
      emergency department. Prognosis of cardiac rupture depends largely on the
      mechanism of injury, location of injury, signs of life: vital signs, and
      availability of timely intervention. When indicated, hesitation should be
      avoided. Expedient cardiac exposure is essential and leads to better results with
      improved survival rates in patients with blunt cardiac rupture. 

PMID- 24936847
TI  - An unusual entry site for a nasal foreign body: a neglected trauma patient.
AB  - Foreign body (FB) in the nose is a frequent situation seen generally among
      children. A variety of objects left in different sites of the nose has been
      reported in the literature. Insertion of a FB to the nose is generally via the
      anterior nares. In this report, an unusual entry site for a nasal FB in a
      neglected trauma patient is presented. FB should be suspected and investigated in
      children after penetrating facial injury. 

PMID- 24936848
TI  - [Occipital condyle fractures: a case report].
AB  - Occipital condyle fractures are rare, and conservative treatment is sufficient
      for many cases. Surgical treatment may be required if the condyle fracture is
      accompanied by atlantooccipital dislocation. Unfortunately, condyle fracture
      generally cannot be diagnosed with X-ray in the emergency department. Recently,
      computed tomography scans have been used more frequently, and enable easier
      diagnosis of these types of fractures. In this report, we describe a patient who
      admitted to our emergency department after a major trauma. She complained of neck
      pain, and maxillofacial trauma was more evident. Her cervical X-rays were normal,
      but cervical computed tomography revealed unilateral occipital condyle fracture. 

PMID- 24936849
TI  - Biologic agents and the therapy of chronic spontaneous urticaria.
AB  - PURPOSE OF REVIEW: Chronic spontaneous urticaria (CSU) has been traditionally
      managed with antihistamines. Over the years, studies using different formulations
      and dosing regimens have delineated the limits of their effectiveness, thus
      emphasizing the need for alternative therapeutic approaches. Data keep
      accumulating that the monoclonal anti-immunoglobulin E antibody omalizumab, until
      recently reserved for the treatment of severe atopic asthma, may have a
      beneficial therapeutic and safety profile for CSU cases resistant to the effect
      of antihistamines. RECENT FINDINGS: Since the beginning of 2013, a host of
      studies have been published paving the way for licensing of omalizumab for the
      treatment of CSU. Dose-finding studies have indicated 300 mg monthly as a
      possible optimal treatment regimen. Efficacy proving randomized controlled trials
      were further supported by open-label studies confirming its effectiveness in real
      life. One report has been published so far presenting positive data about the use
      of another biologic agent, rituximab, depleting the blood stream of B cells, in
      patients with CSU. SUMMARY: New convincing evidence in support of the efficacy
      and safety of omalizumab in the treatment of CSU has accumulated over the past
      year, providing another tool for coping with the antihistamine-resistant cases.

PMID- 24936850
TI  - The importance of hapten-protein complex formation in the development of drug
      allergy.
AB  - PURPOSE OF REVIEW: Drug allergy is an adverse drug reaction that is immune
      mediated. Immune activation can occur when drugs or haptens bind covalently to
      proteins and then act as antigens. The purpose of this review is to summarize the
      recent data on the formation of hapten-protein complexes and to assess the
      importance of these complexes in the generation of drug allergy. RECENT FINDINGS:
      The formation of hapten-protein complexes by drugs and their reactive metabolites
      has largely been investigated using model proteins such as human serum albumin.
      Precise identification of the structure of the hapten and the resulting modified
      residue(s) in the protein has been undertaken for a small number of drugs, such
      as p-phenylenediamine, nevirapine, carbamazepine, beta-lactams and abacavir. Some
      progress has also been made in identifying hapten-protein complexes in the serum
      of patients with allergy. SUMMARY: Drug-specific T cells have been isolated from
      different patients with allergy. Formation of hapten-protein complexes, their
      processing and antigen presentation have been implicated in the development of
      drug allergy to p-phenylenediamine, sulfonamides and beta-lactams. However,
      evidence also supports the pi mechanism of immune activation wherein drugs
      interact directly with immune receptors. Thus, multiple mechanisms of immune
      activation may occur for the same drug.

PMID- 24936851
TI  - Allergy immunotherapy: what is the evidence for cost saving?
AB  - PURPOSE OF REVIEW: Given the widespread prevalence of allergic disease, its
      substantially associated clinical and economic burden, the unique disease
      modifying benefits of allergy immunotherapy (AIT), and increased availability of
      sublingual immunotherapy (SLIT), a critical update of the evidence for AIT
      related cost savings [for both subcutaneous immunotherapy (SCIT) and SLIT] is
      particularly relevant and timely. The present article reviews the evidence for
      SCIT-related and SLIT-related cost savings derived from a systematic review of
      the published literature. RECENT FINDINGS: Examined were 24 publications
      pertaining to the health economics of AIT. Except for one early study comparing
      the costs of AIT to symptomatic drug treatment (SDT), the remainder provide
      compelling evidence for AIT cost savings (whether SCIT or SLIT) over SDT.
      Furthermore, of the six studies comparing cost outcomes of SLIT to SCIT, four
      reported cost savings favoring SLIT. SUMMARY: This review, spanning research from
      Southern Europe, Scandinavia, Northern Europe, North America, and the Czech
      Republic, encompasses a range of perennial and seasonal allergic conditions,
      including allergic asthma, allergic rhinitis with or without asthma, and
      rhinoconjunctivitis with or without allergic rhinitis due to house dust mite,
      grass or ragweed pollen, or a mixture of various allergens. All but one study
      compellingly demonstrate cost savings conferred by AIT over SDT.

PMID- 24936852
TI  - Update on the understanding, diagnosis and tailored management of anaphylaxis:
      making progress.

PMID- 24936853
TI  - Supporting health in the Hyogo Framework for Action-2.

PMID- 24936854
TI  - An extended phenacene-type molecule, [8]phenacene: synthesis and transistor
      application.
AB  - A new phenacene-type molecule, [8]phenacene, which is an extended zigzag chain of
      coplanar fused benzene rings, has been synthesised for use in an organic field
      effect transistor (FET). The molecule consists of a phenacene core of eight
      benzene rings, which has a lengthy pi-conjugated system. The structure was
      verified by elemental analysis, solid-state NMR, X-ray diffraction (XRD) pattern,
      absorption spectrum and photoelectron yield spectroscopy (PYS). This type of
      molecule is quite interesting, not only as pure chemistry but also for its
      potential electronics applications. Here we report the physical properties of
      [8]phenacene and its FET application. An [8]phenacene thin-film FET fabricated
      with an SiO2 gate dielectric showed clear p-channel characteristics. The highest
      MU achieved in an [8]phenacene thin-film FET with an SiO2 gate dielectric is 1.74
      cm(2) V(-1) s(-1), demonstrating excellent FET characteristics; the average MU
      was evaluated as 1.2(3) cm(2) V(-1) s(-1). The MU value in the [8]phenacene
      electric-double-layer FET reached 16.4 cm(2) V(-1) s(-1), which is the highest
      reported in EDL FETs based on phenacene-type molecules; the average MU was
      evaluated as 8(5) cm(2) V(-1) s(-1). The MU values recorded in this study show
      that [8]phenacene is a promising molecule for transistor applications.

PMID- 24936855
TI  - Experimental verification of ion range calculation in a treatment planning system
      using a flat-panel detector.
AB  - Heavy ion-beam therapy is a highly precise radiation therapy exploiting the
      characteristic interaction of ions with matter. The steep dose gradient of the
      Bragg curve allows the irradiation of targets with high-dose and a narrow dose
      penumbra around the target, in contrast to photon irradiation. This, however,
      makes heavy ion-beam therapy very sensitive to minor changes in the range
      calculation of the treatment planning system, as it has a direct influence on the
      outcome of the treatment. Our previous study has shown that ion radiography with
      an amorphous silicon flat-panel detector allows the measurement of the water
      equivalent thickness (WET) of an imaging object with good accuracy and high
      spatial resolution. In this study, the developed imaging technique is used to
      measure the WET distribution of a patient-like phantom, and these results are
      compared to the WET calculation of the treatment planning system. To do so, a
      measured two-dimensional map of the WET of an anthropomorphic phantom was
      compared to WET distributions based on x-ray computed tomography images as used
      in the treatment planning system. It was found that the WET maps agree well in
      the overall shape and two-dimensional distribution of WET values. Quantitatively,
      the ratio of the two-dimensional WET maps shows a mean of 1.004 with a standard
      deviation of 0.022. Differences were found to be concentrated at high WET
      gradients. This could be explained by the Bragg-peak degradation, which is
      measured in detail by ion radiography with the flat-panel detector, but is not
      taken into account in the treatment planning system. Excluding pixels exhibiting
      significant Bragg-peak degradation, the mean value of the ratio was found to be
      1.000 with a standard deviation of 0.012. Employment of the amorphous silicon
      flat-panel detector for WET measurements allows us to detect uncertainties of the
      WET determination in the treatment planning process. This makes the investigated
      technique a very helpful tool to study the WET determination of critical and
      complex phantom cases. 

PMID- 24936857
TI  - The nexus of food, energy, and water.
AB  - The Earth's population is expected to exceed 9 billion by 2050, posing
      significant challenges in meeting human needs while minimally affecting the
      environment. To support this population, we will need secure and safe sources of
      food, energy, and water. The nexus of food, energy, and water is one of the most
      complex, yet critical, issues that face society. There is no more land to
      exploit, and the supply of fresh water in some areas of the world limits the use
      of land for food. All solutions must also deal with the overlay of global climate
      change. Meeting current and future populations needs will require security in
      food, energy, and water supplies. A nexus approach is needed to improve food,
      energy, and water security integrating the management of the limited resources
      while transitioning to a more "green" economy, which provides adequate food,
      energy, and water for the expanding human population. 

PMID- 24936859
TI  - Pt skin on AuCu intermetallic substrate: a strategy to maximize Pt utilization
      for fuel cells.
AB  - The dependence on Pt catalysts has been a major issue of proton-exchange membrane
      (PEM) fuel cells. Strategies to maximize the Pt utilization in catalysts include
      two main approaches: to put Pt atoms only at the catalyst surface and to further
      enhance the surface-specific catalytic activity (SA) of Pt. Thus far there has
      been no practical design that combines these two features into one single
      catalyst. Here we report a combined computational and experimental study on the
      design and implementation of Pt-skin catalysts with significantly improved SA
      toward the oxygen reduction reaction (ORR). Through screening, using density
      functional theory (DFT) calculations, a Pt-skin structure on AuCu(111) substrate,
      consisting of 1.5 monolayers of Pt, is found to have an appropriately weakened
      oxygen affinity, in comparison to that on Pt(111), which would be ideal for ORR
      catalysis. Such a structure is then realized by substituting the Cu atoms in
      three surface layers of AuCu intermetallic nanoparticles (AuCu iNPs) with Pt. The
      resulting Pt-skinned catalyst (denoted as Pt(S)AuCu iNPs) has been characterized
      in depth using synchrotron XRD, XPS, HRTEM, and HAADF-STEM/EDX, such that the Pt
      skin structure is unambiguously identified. The thickness of the Pt skin was
      determined to be less than two atomic layers. Finally the catalytic activity of
      Pt(S)AuCu iNPs toward the ORR was measured via rotating disk electrode (RDE)
      voltammetry through which it was established that the SA was more than 2 times
      that of a commercial Pt/C catalyst. Taking into account the ultralow Pt loading
      in Pt(S)AuCu iNPs, the mass-specific catalytic activity (MA) was determined to be
      0.56 A/mg(Pt)@0.9 V, a value that is well beyond the DOE 2017 target for ORR
      catalysts (0.44 A/mg(Pt)@0.9 V). These findings provide a strategic design and a
      realizable approach to high-performance and Pt-efficient catalysts for fuel
      cells.

PMID- 24936858
TI  - Fetal growth cessation in late pregnancy: its impact on predicted size parameters
      used to classify small for gestational age neonates.
AB  - OBJECTIVE: To evaluate the impact of late 3rd trimester fetal growth cessation on
      anatomical birth characteristic predictions used in classifying SGA neonates.
      METHODS: A prospective longitudinal study was performed in 119 pregnancies with
      normal neonatal growth outcomes. Seven biometric parameters were measured at 3-4
      weeks intervals using 3D ultrasonography. Rossavik size models were determined to
      predict birth characteristics at different ages. Percent Differences (% Diff)
      were calculated from predicted and measured birth characteristics. Growth
      Cessation Ages (GCA) were identified when no systematic change in % Diff values
      occurred after specified prediction ages. Systematic and random prediction errors
      were compared using different assumptions about the GCA. Predicted and measured
      size parameters were used to determine six new Growth Potential Realization Index
      (GPRI) reference ranges. Five were used to sub-classify 34 SGA neonates (weight <
      10th percentile) based on the number of abnormal GPRI values. RESULTS: Growth
      cessation ages were 38 weeks for HC, AC, mid-thigh circumference, estimated
      weight and mid-arm circumference. Crown-heel length GCA was 38.5 weeks. At GCA,
      birth characteristics had prediction errors that varied from 0.08 +/- 3.4% to
      15.7 +/- 9.1% and zero % Diff slopes after 38 weeks. Assuming growth to delivery
      gave increased systematic and random prediction errors as well as positive % Diff
      slopes after 38 weeks, MA. Seventeen of the SGA neonates had 0 or 1 abnormal GPRI
      values [Subgroup 1] and 17 others had 2 or more abnormal values [Subgroup 2]. In
      Subgroup 1, 4/85 (4.7%) of GPRI's were abnormal while in Subgroup 2, 43/85
      (50.6%) were abnormal. Use of only one type of GPRI for SGA subclassification
      resulted in substantial false negative and some false positive rates when
      compared to subclassification based on all five GPRI values. CONCLUSIONS: Growth
      cessation occurred at approximately 38 weeks for all six birth characteristics
      studied. SGA neonates can be separated into normal and growth restricted
      subgroups based on the frequency of abnormal GPRI values (GPRI Profile
      Classification).

PMID- 24936860
TI  - Nocardia brasiliensis induces formation of foamy macrophages and dendritic cells
      in vitro and in vivo.
AB  - Foamy cells have been described in various infectious diseases, for example in
      actinomycetoma induced by Nocardia brasiliensis. These cells are generally
      considered to be macrophages, although they present dendritic cell (DC)-specific
      surface markers. In this study, we determined and confirmed the lineage of
      possible precursors of foamy cells in vitro and in vivo using an experimental
      actinomycetoma model in BALB/c mice. Bone marrow-derived macrophages (BMDM) or DC
      (BMDC) were infected in vitro with N. brasiliensis or labeled with
      carboxyfluorescein diacetate succinimidyl ester (CFSE). Both, macrophages and DC,
      differentiated into foamy cells after in vitro infection. CFSE-labeled BMDM or
      BMDC were tested for phagocytosis and CD11c/CD11b receptors markers expression
      before being transferred into the actinomycetoma lesion site of infected mice. In
      vivo studies showed that BMDM and BMDC were traced at the site where foamy cells
      are present in the experimental actinomycetoma. Interestingly, many of the
      transferred BMDM and BMDC were stained with the lipid-droplet fluorophore Nile
      Red. In conclusion, macrophages and DC cells can be differentiated into foamy
      cells in vitro and in vivo during N. brasiliensis infection. 

PMID- 24936861
TI  - Oral administration of heat-inactivated Lactobacillus plantarum K37 modulated
      airway hyperresponsiveness in ovalbumin-sensitized BALB/c mice.
AB  - This study aimed to investigate the anti-allergic effects of Lactobacillus
      plantarum K37 (K37) on airway hyperresponsiveness (AHR) and systemic allergic
      responses in ovalbumin (OVA)-sensitized and -challenged BALB/c mice. Heat
      inactivated K37 (105, 107, and 109 CFU/mouse, day) were orally administered to
      OVA-sensitized BALB/c mice to investigate their effects on AHR, immunoglobulin
      (Ig) and cytokine production. The results showed that K37 dose-dependently
      lowered the serum levels of IgE, OVA-specific IgE and OVA-specific IgG1,
      ameliorated AHR induced by methacholine and suppressed eosinophil infiltration in
      bronchoalveolar lavage fluid (BALF). The cytokine production in spleen cells
      culture and BALF showed that K37 drove the immune responses toward T-helper cell
      type 1 (Th1) responses, elevated levels of IL-2 and IFN-gamma, and reduced of IL
      4, IL-5 and IL-13. K37 also improved cell infiltration in lung sections. Our
      results demonstrated that oral administration of K37 alleviated effectively the
      allergic responses in vivo. Thus, K37 can be a good source material and a
      promising candidate for prophylactic and therapeutic treatments of allergic
      diseases, like asthma. 

PMID- 24936863
TI  - Interactions of seedborne bacterial pathogens with host and non-host plants in
      relation to seed infestation and seedling transmission.
AB  - The ability of seed-borne bacterial pathogens (Acidovorax citrulli, Clavibacter
      michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato, Xanthomonas
      euvesicatoria, and Pseudomonas syringae pv. glycinea) to infest seeds of host and
      non-host plants (watermelon, tomato, pepper, and soybean) and subsequent pathogen
      transmission to seedlings was investigated. A non-pathogenic, pigmented strain of
      Serratia marcescens was also included to assess a null-interacting situation with
      the same plant species. Flowers of host and non-host plants were inoculated with
      1 * 10(6) colony forming units (CFUs)/flower for each bacterial species and
      allowed to develop into fruits or umbels (in case of onion). Seeds harvested from
      each host/non-host bacterial species combination were assayed for respective
      bacteria by plating on semi-selective media. Additionally, seedlots for each
      host/non-host bacterial species combination were also assayed for pathogen
      transmission by seedling grow-out (SGO) assays under greenhouse conditions. The
      mean percentage of seedlots infested with compatible and incompatible pathogens
      was 31.7 and 30.9% (by plating), respectively and they were not significantly
      different (P = 0.67). The percentage of seedlots infested with null-interacting
      bacterial species was 16.8% (by plating) and it was significantly lower than the
      infested lots generated with compatible and incompatible bacterial pathogens (P =
      0.03). None of the seedlots with incompatible/null-interacting bacteria developed
      symptoms on seedlings; however, when seedlings were assayed for epiphytic
      bacterial presence, 19.5 and 9.4% of the lots were positive, respectively. These
      results indicate that the seeds of non-host plants can become infested with
      incompatible and null-interacting bacterial species through flower colonization
      and they can be transmitted via epiphytic colonization of seedlings. In addition,
      it was also observed that flowers and seeds of non-host plants can be colonized
      by compatible/incompatible/null-interacting bacteria to higher populations;
      however, the level of colonization differed significantly depending on the type
      of bacterial species used.

PMID- 24936864
TI  - Patterns of recombination in HIV-1M are influenced by selection disfavouring the
      survival of recombinants with disrupted genomic RNA and protein structures.
AB  - Genetic recombination is a major contributor to the ongoing diversification of
      HIV. It is clearly apparent that across the HIV-genome there are defined
      recombination hot and cold spots which tend to co-localise both with genomic
      secondary structures and with either inter-gene boundaries or intra-gene domain
      boundaries. There is also good evidence that most recombination breakpoints that
      are detectable within the genes of natural HIV recombinants are likely to be
      minimally disruptive of intra-protein amino acid contacts and that these
      breakpoints should therefore have little impact on protein folding. Here we
      further investigate the impact on patterns of genetic recombination in HIV of
      selection favouring the maintenance of functional RNA and protein structures. We
      confirm that chimaeric Gag p24, reverse transcriptase, integrase, gp120 and Nef
      proteins that are expressed by natural HIV-1 recombinants have significantly
      lower degrees of predicted folding disruption than randomly generated
      recombinants. Similarly, we use a novel single-stranded RNA folding disruption
      test to show that there is significant, albeit weak, evidence that natural HIV
      recombinants tend to have genomic secondary structures that more closely resemble
      parental structures than do randomly generated recombinants. These results are
      consistent with the hypothesis that natural selection has acted both in the short
      term to purge recombinants with disrupted RNA and protein folds, and in the
      longer term to modify the genome architecture of HIV to ensure that recombination
      prone sites correspond with those where recombination will be minimally
      deleterious. 

PMID- 24936865
TI  - RNA-Seq analysis implicates detoxification pathways in ovine mycotoxin
      resistance.
AB  - Mycotoxin induced hepatoxocity has been linked to oxidative stress, resulting
      from either an increase in levels of reactive oxygen species (ROS) above normal
      levels and/or the suppression of antioxidant protective pathways. However, few
      detailed molecular studies of mycotoxicoses in animals have been carried out.
      This study use current RNA-seq based approaches to investigate the effects of
      mycotoxin exposure in a ruminant model. Having first assembled a de novo
      reference transcriptome, we use RNA-Seq technology to define in vivo hepatic gene
      expression changes resulting from mycotoxin exposure in relationship to
      pathological effect. As expected, characteristic oxidative stress related gene
      expression is markedly different in animals exhibiting poorer outcomes. However,
      expression of multiple genes critical for detoxification, particularly members of
      the cytochrome P450 gene family, was significantly higher in animals exhibiting
      mycotoxin tolerance ('resistance'). Further, we present novel evidence for the
      amplification of Wnt signalling pathway activity in 'resistant' animals,
      resulting from the marked suppression of multiple key Wnt inhibitor genes.
      Notably, 'resistance' may be determined primarily by the ability of an individual
      to detoxify secondary metabolites generated by the metabolism of mycotoxins and
      the potentiation of Wnt signalling may be pivotal to achieving a favourable
      outcome upon challenge. 

PMID- 24936866
TI  - Nuclear NF-kappaB p65 in peripheral blood mononuclear cells correlates with
      urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.
AB  - AIMS: To investigate if nuclear NF-kappaB p65 expression in ex vivo isolated
      peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and
      the severity of type 2 diabetic nephropathy. METHODS: According to their urinary
      albumin-to-creatinine ratio (uACR), 107 patients with type 2 diabetes (eGFR >60
      ml/min) were divided into normal albuminuria group (DN0 group, 38 cases),
      microalbuminuria group (DN1 group, 38 cases), and macroalbuminuria group (DN2
      group, 31 cases), compared with matched healthy normal control group (NC group,
      30 cases). Nuclear NF-kappaB p65 protein expression levels in peripheral blood
      mononuclear cells were detected by western blotting. Real-time quantitative
      polymerase chain reaction was used to detect NF-kappaB p65 mRNA expression and
      ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS:
      Nuclear NF-kappaB p65 protein and NF-kappaB p65 mRNA expression levels in
      peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all
      significantly higher in all diabetes groups as compared with NC group. In
      particular, the increase of nuclear NF-kappaB p65 protein and NF-kappaB p65 mRNA
      expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of
      type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson
      correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were
      positively correlated with nuclear NF-kappaB p65 protein or NF-kappaB p65 mRNA
      levels. Stepwise multiple regression analysis showed that nuclear NF-kappaB p65
      protein or NF-kappaB p65 mRNA was an independent variable for urinary MCP-1/Cr,
      and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION:
      Our research demonstrates that nuclear NF-kappaB p65 protein and mRNA expressions
      in ex vivo isolated peripheral blood mononuclear cells well correlate with
      urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

PMID- 24936867
TI  - A toll-like receptor 9 antagonist improves bladder function and white matter
      sparing in spinal cord injury.
AB  - Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As
      current therapies do not adequately alleviate functional deficits, the
      development of new and more effective approaches is of critical importance. Our
      earlier investigations indicated that intrathecal administration of a toll-like
      receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide
      2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury
      diminished neuropathic pain but did not alter locomotor deficits. These changes
      were paralleled by a decrease in the pro-inflammatory response at the injury
      epicenter. Using the same SCI paradigm and treatment regimen, the current studies
      investigated the effects of the TLR9 antagonist on bladder function. We report
      that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates
      bladder morphopathology without affecting kidney function. A significant
      improvement in white matter sparing was also observed, most likely due to
      alterations in the inflammatory milieu. These findings indicate that the TLR9
      antagonist has beneficial effects not only in reducing sensory deficits, but also
      on bladder dysfunction and tissue preservation. Thus, modulation of innate immune
      receptor signaling in the spinal cord can impact the effects of SCI.

PMID- 24936868
TI  - The use of mixed generalized additive modeling to assess the effect of
      temperature on the usage of emergency electrocardiography examination among the
      elderly in Shanghai.
AB  - BACKGROUND: Acute coronary artery diseases have been observed to be associated
      with some meteorological variables. But few of the previous studies considered
      autocorrelated outcomes. Electrocardiography is a widely used tool in the initial
      diagnosis of acute cardiovascular events, and emergency electrocardiography
      counts were shown to be highly correlated with acute myocardial infarction in our
      pilot study, hence a good index of prediction for acute cardiovascular events
      morbidity among the elderly. To indirectly assess the impact of temperature on
      the number of acute cardiovascular events, we studied the association between
      temperature and emergency electrocardiography counts while considering
      autocorrelated nature of the response variables. METHODS: We collected daily
      emergency electrocardiography counts for elderly females and males in Shanghai
      from 2007 to middle 2012, and studied temperature and other effects on these data
      using Mixed Generalized Additive Modelling methods. Delayed temperature effect
      distribution was described as the weighted average of the temperatures within 3
      days before the counts was recorded. Autoregressive random effects were used in
      the model to describe the autocorrelation of the response variables. MAIN
      RESULTS: Temperature effect was observed to be piecewise linearly associated with
      the logarithm of emergency electrocardiography counts. The optimal weights of the
      delayed temperature effect distribution were obtained from the model estimation.
      The weights of lag-1 were the maximums, significantly greater than the weights of
      lag-2 and lag-3 for both females and males. The model showed good fit with R2
      values of 0.860 for females and 0.856 for males. CONCLUSION: From the mixed
      generalized additive model, we infer that during cold and mild days, the number
      of emergency electrocardiography counts increase as temperature effect decreases,
      while during hot days, counts increase as temperature effect increases. Similar
      properties could be inferred for the occurrence of cardiovascular events.

PMID- 24936869
TI  - Antarctica's protected areas are inadequate, unrepresentative, and at risk.
AB  - Antarctica is widely regarded as one of the planet's last true wildernesses,
      insulated from threat by its remoteness and declaration as a natural reserve
      dedicated to peace and science. However, rapidly growing human activity is
      accelerating threats to biodiversity. We determined how well the existing
      protected-area system represents terrestrial biodiversity and assessed the risk
      to protected areas from biological invasions, the region's most significant
      conservation threat. We found that Antarctica is one of the planet's least
      protected regions, with only 1.5% of its ice-free area formally designated as
      specially protected areas. Five of the distinct ice-free ecoregions have no
      specially designated areas for the protection of biodiversity. Every one of the
      55 designated areas that protect Antarctica's biodiversity lies closer to sites
      of high human activity than expected by chance, and seven lie in high-risk areas
      for biological invasions. By any measure, including Aichi Target 11 under the
      Convention on Biological Diversity, Antarctic biodiversity is poorly protected by
      reserves, and those reserves are threatened.

PMID- 24936871
TI  - Effect of a reduced-CHO diet on the rate of perceived exertion curve during an
      incremental test.
AB  - The objective of this study was to evaluate the effect of a reduced-carbohydrate
      (reduced-CHO) diet on the rate of perceived exertion (RPE) curve during an
      incremental test. Nine physically active men performed a progressive incremental
      test on a cycle ergometer (25 W . 2 min(-1)) after 72 hr on either a control diet
      (60% CHO) or a reduced-CHO diet (30% CHO). Lactate and RPE thresholds were
      identified using the Dmax method (DmaxLa and DmaxRPE, respectively). Power
      output, heart rate and RPE scores in DmaxLa and DmaxRPE were similar between the
      diets and were not different from each other, regardless of the diet. Lactate
      values were consistently higher (p < .05) in the control diet compared with the
      reduced-CHO diet during power output after the lactate breakpoint; however, they
      were not accompanied by a proportional increase in RPE scores. These results
      suggest that DmaxRPE and DmaxLa are not dissociated after a short-period reduced
      CHO diet, whereas the lactate values after the lactate threshold are reduced with
      a reduced-CHO diet, although they are not accompanied by alterations in RPE.

PMID- 24936872
TI  - Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic
      syndromes: a retrospective cohort study and meta-analysis.
AB  - BACKGROUND: Recent genomic sequencing efforts have identified a number of
      recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to
      disease progression and overall survival, including mutations in isocitrate
      dehydrogenases 1 and 2 (IDH1 and IDH2). METHODS: Pretreatment bone marrow (BM)
      samples were acquired from mononuclear cells in 146 adult patients with de novo
      MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct
      sequencing were performed on exon 4 of IDH1/2 genes and mutation status was
      correlated with overall survival (OS) and leukemia-free survival (LFS). We then
      performed a meta-analysis combining previously published and current studies to
      explore the effect of IDH mutations on OS and LFS in MDS. RESULTS: In our study,
      somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%)
      and were significantly correlated with poorer OS (P = 0.007). IDH mutations were
      specifically associated with a poorer OS in the intermediate-1 risk group by the
      International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we
      discovered decitabine achieved a better therapeutic effect compared to other
      treatments in IDH mutation-positive patients (P = 0.023). We identified six
      previous studies of IDH mutations in MDS. A meta-analysis of these studies
      included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type
      IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations
      were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.
      CONCLUSION: The results from our study and the meta-analysis provide firm
      evidence that IDH mutations are significantly associated with poorer clinical
      outcomes in MDS. Identification of IDH mutations may be pivotal for better risk
      stratification in MDS patients and improving IPSS score. Additionally,
      hypomethylating agents may be an effective treatment option for MDS patients with
      IDH mutations.

PMID- 24936870
TI  - Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may
      influence the clinical manifestation of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by progressive cognitive decline
      associated with a featured neuropathology (neuritic plaques and neurofibrillary
      tangles). Several studies have implicated oxidative damage to DNA, DNA repair,
      and altered cell-cycle regulation in addition to cell death in AD post-mitotic
      neurons. However, there is a lack of studies that systematically assess those
      biological processes in patients with AD neuropathology but with no evidence of
      cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG,
      H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin
      B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and
      cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a
      tissue microarray (TMA) composed of three groups: I) "clinical-pathological AD"
      (CP-AD)--subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and
      clinical dementia (CDR >= 2, IQCODE>3.8); II) "pathological AD" (P-AD)--subjects
      with neuropathological AD (Braak >= IV and CERAD = B or C) and without cognitive
      impairment (CDR 0, IQCODE<3.2); and III) "normal aging" (N)--subjects without
      neuropathological AD (Braak <= II and CERAD 0 or A) and with normal cognitive
      function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA
      damage are present in all groups. However, significant reductions in DNA repair
      and cell-cycle inhibition markers and increases in cell-cycle progression and
      cell death markers in subjects with CP-AD were detected when compared to both P
      AD and N groups, whereas there were no significant differences in the studied
      markers between P-AD individuals and N subjects. This study indicates that, even
      in the setting of pathological AD, healthy cognition may be associated with a
      preserved repair to DNA damage, cell-cycle regulation, and cell death in post
      mitotic neurons.

PMID- 24936873
TI  - An in vitro study on the effect of free amino acids alone or in combination with
      nisin on biofilms as well as on planktonic bacteria of Streptococcus mutans.
AB  - Free D-amino acids (D-AAs) are one of the most striking features of the
      peptidoglycan composition in bacteria and play a key role in regulating and
      disassembling bacterial biofilms. Previous studies have indicated that the
      antimicrobial peptide nisin can inhibit the growth of the cariogenic bacteria
      Streptococcus mutans. The present study investigated the effect of free amino
      acids either alone or in combination with nisin on biofilm and on planktonic S.
      mutans bacteria. The results of the MIC and MBC analyses showed that D-cysteine
      (Cys), D- or L-aspartic acid (Asp), and D- or L-glutamic acid (Glu) significantly
      improve the antibacterial activity of nisin against S. mutans and that the
      mixture of D-Cys, D-Asp, and D-Glu (3D-AAs) and the mixture of L-Cys, L-Asp, and
      L-Glu (3L-AAs) at a concentration of 40 mM can prevent S. mutans growth. Crystal
      violet staining showed that the D- or L-enantiomers of Cys, Asp, and Glu at a
      concentration of 40 mM can inhibit the formation of S. mutans biofilms, and their
      mixture generated a stronger inhibition than the components alone. Furthermore,
      the mixture of the three D-AAs or L-AAs may improve the antibacterial activity of
      nisin against S. mutans biofilms. This study underscores the potential of free
      amino acids for the enhancement of the antibacterial activity of nisin and the
      inhibition of the cariogenic bacteria S. mutans and biofilms. 

PMID- 24936875
TI  - OccuPeak: ChIP-Seq peak calling based on internal background modelling.
AB  - ChIP-seq has become a major tool for the genome-wide identification of
      transcription factor binding or histone modification sites. Most peak-calling
      algorithms require input control datasets to model the occurrence of background
      reads to account for local sequencing and GC bias. However, the GC-content of
      reads in Input-seq datasets deviates significantly from that in ChIP-seq
      datasets. Moreover, we observed that a commonly used peak calling program
      performed equally well when the use of a simulated uniform background set was
      compared to an Input-seq dataset. This contradicts the assumption that input
      control datasets are necessary to fatefully reflect the background read
      distribution. Because the GC-content of the abundant single reads in ChIP-seq
      datasets is similar to those of randomly sampled regions we designed a peak
      calling algorithm with a background model based on overlapping single reads. The
      application, OccuPeak, uses the abundant low frequency tags present in each ChIP
      seq dataset to model the background, thereby avoiding the need for additional
      datasets. Analysis of the performance of OccuPeak showed robust model parameters.
      Its measure of peak significance, the excess ratio, is only dependent on the tag
      density of a peak and the global noise levels. Compared to the commonly used peak
      calling applications MACS and CisGenome, OccuPeak had the highest sensitivity in
      an enhancer identification benchmark test, and performed similar in an overlap
      tests of transcription factor occupation with DNase I hypersensitive sites and
      H3K27ac sites. Moreover, peaks called by OccuPeak were significantly enriched
      with cardiac disease-associated SNPs. OccuPeak runs as a standalone application
      and does not require extensive tweaking of parameters, making its use
      straightforward and user friendly. AVAILABILITY: http://occupeak.hfrc.nl.

PMID- 24936876
TI  - Immune response varies with rate of dispersal in invasive cane toads (Rhinella
      marina).
AB  - What level of immunocompetence should an animal maintain while undertaking long
      distance dispersal? Immune function (surveillance and response) might be down
      regulated during prolonged physical exertion due to energy depletion, and/or to
      avoid autoimmune reactions arising from damaged tissue. On the other hand,
      heightened immune vigilance might be favored if the organism encounters novel
      pathogens as it enters novel environments. We assessed the links between immune
      defense and long-distance movement in a population of invasive cane toads
      (Rhinella marina) in Australia. Toads were radio-tracked for seven days to
      measure their activity levels and were then captured and subjected to a suite of
      immune assays. Toads that moved further showed decreased bacteria-killing ability
      in their plasma and decreased phagocytic activity in their whole blood, but a
      heightened skin-swelling response to phytohemagglutinin. Baseline and post-stress
      corticosterone levels were unrelated to distance moved. Thus, long-distance
      movement in cane toads is associated with a dampened response in some systems and
      enhanced response in another. This pattern suggests that sustained activity is
      accompanied by trade-offs among immune components rather than an overall down or
      up-regulation. The finding that high mobility is accompanied by modification of
      the immune system has important implications for animal invasions. 

PMID- 24936877
TI  - Engineering bacterial phenylalanine 4-hydroxylase for microbial synthesis of
      human neurotransmitter precursor 5-hydroxytryptophan.
AB  - 5-Hydroxytryptophan (5-HTP) is a drug that is clinically effective against
      depression, insomnia, obesity, chronic headaches, etc. It is only commercially
      produced by the extraction from the seeds of Griffonia simplicifolia because of a
      lack of synthetic methods. Here, we report the efficient microbial production of
      5-HTP via combinatorial protein and metabolic engineering approaches. First, we
      reconstituted and screened prokaryotic phenylalanine 4-hydroxylase activity in
      Escherichia coli. Then, sequence- and structure-based protein engineering
      dramatically shifted its substrate preference, allowing for efficient conversion
      of tryptophan to 5-HTP. Importantly, E. coli endogenous tetrahydromonapterin
      (MH4) could be utilized as the coenzyme, when a foreign MH4 recycling mechanism
      was introduced. Whole-cell bioconversion allowed the high-level production of 5
      HTP (1.1-1.2 g/L) from tryptophan in shake flasks. On this basis, metabolic
      engineering efforts were further made to achieve the de novo 5-HTP biosynthesis
      from glucose. This work not only holds great scale-up potential but also
      demonstrates a strategy for expanding the native metabolism of microorganisms. 

PMID- 24936878
TI  - An integrative review of guidelines for anal cancer screening in HIV-infected
      persons.
AB  - HIV-infected individuals are 28 times more likely than the general population to
      be diagnosed with anal cancer. An integrative review of recommendations and
      guidelines for anal cancer screening was performed to provide a succinct guide to
      inform healthcare clinicians. The review excluded studies that were of non-HIV
      populations, redundant articles or publications, non-English manuscripts, or
      nonclinical trials. The review found no formal national or international
      guidelines exist for routine screening of anal cancer for HIV-infected
      individuals. To date, no randomized control trial provides strong evidence
      supporting efficaciousness and effectiveness of an anal cancer screening program.
      The screening recommendations from seven international-, national-, and state
      based reports were reviewed and synthesized in this review. These guidelines
      suggest anal cancer screening, albeit unproven, may be beneficial at decreasing
      the incidence of anal cancer. This review highlights the paucity of screening
      related research and is an area of need to provide clear direction and to define
      standard of care for anal cancer screening in HIV-infected persons.

PMID- 24936879
TI  - A new affinity gel for the purification of alpha-carbonic anhdrases.
AB  - The new affinity gel reported in this study was prepared using EUPERGIT C250L as
      a chromatographic bed material, to which etylenediamine spacer arms were attached
      to prevent steric hindrance between the matrix and ligand, and to facilitate
      effective binding of the CA-specific ligand, of the aromatic sulfonamide type for
      the purification of alpha-carbonic anhydrases (Cas; EC 4.2.1.1). Indeed, the
      aminoethyl moieties of the affinity gel were derivatized by reaction with 4
      isothiocyanatobenzenesulfonamide, with the formation of a thiourea-based gel,
      having inhibitory effects against CAs. Both bovine erythrocyte carbonic anhydrase
      BCA and human (h) erythrocyte CA isoforms I, II (hCA I and II) have been purified
      from hemolysates, by using this affinity gel. The greatest purification fold and
      column yields for BCA and for cytosolic (hCA I + II) enzymes were of 181-fold
      (21.07%) and 184-fold (9.49%), respectively. Maximum binding was achieved at 15 
      degrees C and I = 0.3 ionic strength for alpha-carbonic anhydrases.

PMID- 24936880
TI  - Superior cathode of sodium-ion batteries: orthorhombic V2O5 nanoparticles
      generated in nanoporous carbon by ambient hydrolysis deposition.
AB  - For the first time, we demonstrate that orthorhombic V2O5 can exhibit superior
      electrochemical performance in sodium ion batteries when uniformly coated inside
      nanoporous carbon. The encapsulated V2O5 shows a specific capacity as high as 276
      mAh/g, while the whole nanocomposite exhibits a capacity of 170 mAh/g. The V2O5/C
      composite was fabricated by a novel ambient hydrolysis deposition that features
      sequential water vapor adsorption in nanoporous carbon, followed by a hydrolysis
      reaction, exclusively inside the nanopores. The unique structure of the
      nanocomposite significantly enhances the capacity as well as the rate performance
      of orthorhombic V2O5 where the composite retains a capacity of over 90 mAh/g at a
      current rate of 640 mA/g. Furthermore, by calculating, we also revealed that a
      large portion of the sodium-ion storage, particularly at high current rates, is
      due to the V2O5 pseudocapacitance.

PMID- 24936881
TI  - First european meeting for diseases algorithms on the psychopharmacology of
      psychiatric.

PMID- 24936882
TI  - Treatment of panic disorder: Algorithms for pharmacotherapy.

PMID- 24936883
TI  - Treatment of obsessive compulsive disorder: Algorithms for pharmacotherapy.

PMID- 24936885
TI  - International psychopharmacology algorithm project: algorithms in
      psychopharmacology.

PMID- 24936884
TI  - Treatment of schizophrenic disorders: Algorithms for acute pharmacotherapy.

PMID- 24936886
TI  - Treatment of unipolar major depression: Algorithms for pharmacotherapy.

PMID- 24936887
TI  - Treatment of bipolar depressive mood disorders: Algorithms for pharmacotherapy.

PMID- 24936888
TI  - Growth and body composition in Brazilian female rhythmic gymnastics athletes.
AB  - The aim was to analyse the physical growth and body composition of rhythmic
      gymnastics athletes relative to their level of somatic maturation. This was a
      cross-sectional study of 136 athletes on 23 teams from Brazil. Mass, standing
      height and sitting height were measured. Fat-free and fat masses, body fat
      percentages and ages of the predicted peak height velocity (PHV) were calculated.
      The z scores for mass were negative during all ages according to both WHO and
      Brazilian references, and that for standing height were also negative for all
      ages according to WHO reference but only until 12 years old according to
      Brazilian reference. The mean age of the predicted PHV was 12.1 years. The mean
      mass, standing and sitting heights, body fat percentage, fat-free mass and fat
      mass increased significantly until 4 to 5 years after the age of the PHV.
      Menarche was reached in only 26% of these athletes and mean age was 13.2 years.
      The mass was below the national reference standards, and the standing height was
      below only for the international reference, but they also had late recovery of
      mass and standing height during puberty. In conclusion, these athletes had a
      potential to gain mass and standing height several years after PHV, indicating
      late maturation.

PMID- 24936889
TI  - Tumaini: reframing hope at a place called Kimbilio.

PMID- 24936890
TI  - Description and evaluation of the first national patient and public involvement
      day for thyroid eye disease in the United Kingdom.
AB  - BACKGROUND: To ensure appropriate patient-focused outcomes, the National
      Institute for Health Research (NIHR) in the United Kingdom has made consultation
      with patients, caregivers, and the public a prerequisite to providing research
      funding. One method of encouraging engagement with research is through patient
      and public involvement (PPI) events. We describe the planning and implementation
      of a PPI day for thyroid eye disease (TED) and evaluate our own event using
      feedback from delegates. METHODS: The Moorfields NIHR Biomedical Research Centre,
      in partnership with TED charities, arranged the first national PPI day for TED in
      the United Kingdom. The event included didactic lectures; pre-event and postevent
      questionnaires; an exhibition with stalls, posters, and an interactive voting
      wall to determine research priorities; focus group sessions to explore patient
      experiences and perceptions of research; and one-on-one interviews recording
      individual patient stories. RESULTS: Of 100 attendees, 70 completed
      questionnaires. When asked whether the day had provided what they wanted, 48 of
      52 (92%) said yes; 3 of 52 (6%) said no. Overall 6 of 52 (12%) rated the event as
      good; 28 of 52 (54%), very good; and 18 of 52 (34%), excellent. Thirty-six
      patients registered to participate in further research, identifying "finding the
      cause for TED," "improving psychological support," and "achieving a better
      cosmetic outcome" as key priorities. A poor understanding of TED among medical
      professionals was a common complaint. CONCLUSIONS: The event received positive
      feedback and achieved its key objective of engaging patients, researchers, and
      clinicians in a two-way discussion about research priorities and improved study
      design. An invaluable insight was gained into patients' needs for a better
      quality of life, and we have demonstrated that important data can be captured
      from such events, providing an evidential basis consistent with the NIHR
      principles of patient-centered research.

PMID- 24936891
TI  - Raman imaging providing insights into chemical composition of lipid droplets of
      different size and origin: in hepatocytes and endothelium.
AB  - In this work, 3D linear Raman spectroscopy was used to study lipid droplets (LDs)
      ex vivo in liver tissue and also in vitro in a single endothelial cell.
      Spectroscopic measurements combined with fluorescence microscopy and/or
      histochemical staining gave complex chemical information about LD composition and
      enabled detailed investigations of the changes occurring in various pathological
      states. Lipid analysis in fatty liver tissue was performed using a dietary mouse
      model of liver steatosis, induced by a high fat diet (HFD). HFD is characterized
      by a high percentage of calories from saturated fat (60%) and reflects closely
      the detrimental effects of dietary habits responsible for increased morbidity due
      to obesity and its complications in well-developed Western societies. Such diets
      lead to obesity, hyperlipidemia, insulin resistance, and steatosis that may also
      be linked to endothelial dysfunction. In the present work, Raman spectroscopy was
      applied to characterized chemical composition of lipid droplets in hepatocytes
      from mice fed HFD and in the endothelium treated with exogenous unsaturated free
      fatty acid (arachidonic acid). The results demonstrate the usefulness of Raman
      spectroscopy to characterize intracellular lipid distribution in 2D and 3D images
      and can be used to determine the degree of saturation. Raman spectroscopy shows
      the potential to be a valuable tool for studying the role of LDs in physiology
      and pathology. The method is generally applicable for the determination of LDs of
      different size, origin, and composition. Moreover, for the first time, the
      process of LD formation in the endothelium was detected and visualized in 3D. 

PMID- 24936894
TI  - Relationship between midweek training measures of testosterone and cortisol
      concentrations and game outcome in professional rugby union matches.
AB  - The aim of this study was to assess the response of salivary-free testosterone
      and cortisol concentrations across selected midweek skill-based training sessions
      and their association with subsequent match outcome 3 days later. Twenty-two
      rugby union players were assessed for salivary-free testosterone and cortisol
      concentrations before and after a midweek training session over 6 consecutive
      weeks. The relative percentage change (response) in the testosterone and cortisol
      concentration and the testosterone to cortisol (T/C) ratio was also determined.
      Game-day analysis consisted of prematch testosterone concentrations and match
      outcome. Data were pooled across the winning (n = 3) and losing (n = 3) outcomes.
      The midweek pretraining T/C ratio was significantly lower (p < 0.01) before a win
      than a loss and the increase in the pre- to post-T/C ratio before a win was
      significant (p < 0.001). The increase in the pre- to post-testosterone
      concentration before a win was also shown to be significant (p < 0.01). However,
      the relative changes in testosterone before games that were won were not
      statistically different to that of games lost (p > 0.01). Significant
      relationships were also demonstrated between game-day pre-testosterone
      concentrations and the midweek cortisol response (r = -0.90, p = 0.01) and
      midweek T/C ratio response (r = 0.90, p = 0.01). In conclusion, a midweek
      measurement of the T/C ratio against a skill-based training session seems to show
      some potential as an early indicator of subsequent successfully executed
      performances in competitive rugby union. If this work is subsequently validated,
      further monitoring of midweek hormone concentrations in response to a mixed
      psychological-physical training session may assist with assessing competitive
      readiness leading up to competition.

PMID- 24936893
TI  - Prevalence of and risk factors for age-related and anterior polar cataracts in a
      Korean population.
AB  - OBJECTIVE: To investigate the potential risk factors associated with nuclear,
      cortical, posterior subcapsular, and anterior polar cataracts (APC) in the Korean
      population. RESEARCH DESIGN AND METHODS: This was a population-based, cross
      sectional study of 7992 adults (over 40 years of age) from the data of the fourth
      annual Korea National Health and Nutrition Examination Survey, performed from
      2007 to 2009. The presence of lens opacity was examined by slit-lamp
      biomicroscopy and evaluated according to LOCS II standard photographs. The
      subtype of cataract present, including nuclear, cortical, posterior subcapsular,
      and anterior polar cataracts, was noted. Multivariable adjusted logistic
      regression analysis was conducted to examine the odds ratio (OR) and 95%
      confidence interval (CI) for association of each specific type of cataract with
      age, sex, health examination, and medical history. RESULTS: The prevalence of
      nuclear, cortical, and posterior subcapsular cataract increased gradually with
      increasing age. However, the prevalence of APC peaked in the 50- to 59-year-old
      subjects. All types of cataract except for APCs were more prevalent in women.
      Oral steroid use was associated with a lower risk of APC. CONCLUSIONS: These
      findings showed the unique characteristics of APC in the Korean population.

PMID- 24936895
TI  - Drive for muscularity and social physique anxiety mediate the perceived ideal
      physique muscle dysmorphia relationship.
AB  - This study examined the mediating role of drive for muscularity and social
      physique anxiety (SPA) in the perceived muscular male ideal physique and muscle
      dysmorphia relationship in weight training men. Men (N = 146, mean +/- SD; age,
      22.8 +/- 5.0 years; weight, 82.0 +/- 11.1 kg; height, 1.80 +/- 0.07 m; body mass
      index, 25.1 +/- 3.0) who participated in weight training completed validated
      questionnaires measuring drive for muscularity, SPA, perceived muscular male
      ideal physique, global muscle dysmorphia, and several characteristics of muscle
      dysmorphia (exercise dependence, diet manipulation, concerns about size/symmetry,
      physique protection behavior, and supplementation). Perceived ideal physique was
      an independent predictor of muscle dysmorphia measures except physique protection
      (coefficients = 0.113-0.149, p <= 0.05). Perceived ideal physique also predicted
      muscle dysmorphia characteristics (except physique protection and diet) through
      the indirect drive for muscularity pathway (coefficients = 0.055-0.116, p <=
      0.05). Perceived ideal physique also predicted size/symmetry concerns and
      physique protection through the indirect drive for muscularity and SPA pathway
      (coefficients = 0.080-0.025, p <= 0.05). These results extend current research by
      providing insights into the way correlates of muscle dysmorphia interact to
      predict the condition. The results also highlight signs (e.g., anxiety about
      muscularity) that strength and conditioning coaches can use to identify at-risk
      people who may benefit from being referred for psychological assistance.

PMID- 24936896
TI  - Verification criteria for the determination of Vo2 MAX in the field.
AB  - The purpose of this study was to evaluate if a verification test (VT) performed
      in the field offers more confident results than do traditional criteria in the
      determination of maximal oxygen uptake ((Equation is included in full-text
      article.)). Twelve amateur runners (age, 36.6 +/- 6.6 years) performed a maximal
      graded field test and after 15 minutes of passive recovery a supramaximal test to
      exhaustion at 105% of their velocity associated with (Equation is included in
      full-text article.)(v(Equation is included in full-text article.)). Traditional
      criteria and 2 different verification criteria were evaluated. Verification
      criteria were (a) maximal oxygen uptake achieved in the VT ((Equation is included
      in full-text article.)) must be <=5% higher than (Equation is included in full
      text article.), and (b) no significant differences of means between tests. All
      participants met the first verification criterion although significant
      differences were found between (Equation is included in full-text article.)and
      (Equation is included in full-text article.)(59.4 +/- 5.1 vs. 56.2 +/- 4.7
      ml.kg.min, p < 0.01). The criteria for the plateau, peak heart rate (HRpeak),
      maximum respiratory exchange ratio (RERmax), and maximum blood lactate
      concentration ([La]max) were satisfied by 75, 66, 92, and 66 of the participants,
      respectively. Kappa coefficients gave a significant and substantial agreement
      beyond chance between traditional criteria (p < 0.001). Despite the substantial
      agreement, traditional criteria induced the rejection of participants that might
      have achieved a true (Equation is included in full-text article.)with HRpeak and
      [La]max being the more stringent criteria for amateur runners. A verification
      protocol in the field using the criterion based on individual analysis is
      recommended.

PMID- 24936897
TI  - Differential effects of 30- vs. 60-second static muscle stretching on vertical
      jump performance.
AB  - It has been proposed that pre-exercise static stretching may reduce muscle force
      and power. Recent systematic and meta-analytical reviews have proposed a
      threshold regarding the effect of short (<45 seconds) and moderate (>=60 seconds)
      stretching durations on subsequent performance in a multi-joint task (e.g., jump
      performance), although its effect on power output remains less clear.
      Furthermore, no single experimental study has explicitly compared the effect of
      short (e.g., 30 seconds) and moderate (60 seconds) durations of continuous static
      stretching on multi-joint performance. Therefore, the aim of the present study
      was determine the effect of acute short- and moderate-duration continuous
      stretching interventions on vertical jump performance and power output. Sixteen
      physically active men (21.0 +/- 1.9 years; 1.7 +/- 0.1 m; 78.4 +/- 12.1 kg)
      volunteered for the study. After familiarization, subjects attended the
      laboratory for 3 testing sessions. In the nonstretching (NS) condition, subjects
      performed a countermovement jump (CMJ) test without a preceding stretching bout.
      In the other 2 conditions, subjects performed 30-second (30SS; 4 minutes) or 60
      second (60SS; 8 minutes) static stretching bouts in calf muscles, hamstrings,
      gluteus maximus, and quadriceps, respectively, followed by the CMJ test. Results
      were compared by repeated-measures analysis of variance. In comparison with NS,
      60SS resulted in a lower CMJ height (-3.4%, p <= 0.05) and average (-2.7%, p <=
      0.05) and peak power output (-2.0%, p <= 0.05), but no difference was observed
      between 30SS and the other conditions (p > 0.05). These data suggest a dose
      dependent effect of stretching on muscular performance, which is in accordance
      with previous studies. The present results suggest a threshold of continuous
      static stretching in which muscular power output in a multi-joint task may be
      impaired immediately following moderate-duration (60 seconds; 8 minutes) static
      stretching while short-duration (30 seconds; 4 minutes) stretching has a
      negligible influence.

PMID- 24936898
TI  - Shoulder proprioception is not related to throwing speed or accuracy in elite
      adolescent male baseball players.
AB  - Understanding factors that influence throwing speed and accuracy is critical to
      performance in baseball. Shoulder proprioception has been implicated in the
      injury risk of throwing athletes, but no such link has been established with
      performance outcomes. The purpose of this study was to describe any relationship
      between shoulder proprioception acuity and throwing speed or accuracy. Twenty
      healthy elite adolescent male baseball players (age, 19.6 +/- 2.6 years), who had
      represented the state of New South Wales in the past 18 months, were assessed for
      bilateral active shoulder proprioception (shoulder rotation in 90 degrees  of arm
      abduction moving toward external rotation using the active movement extent
      discrimination apparatus), maximal throwing speed (MTS, meters per second
      measured via a radar gun), and accuracy (total error in centimeters determined by
      video analysis) at 80 and 100% of MTS. Although proprioception in the dominant
      and nondominant arms was significantly correlated with each other (r = 0.54, p <
      0.01), no relationship was found between shoulder proprioception and performance.
      Shoulder proprioception was not a significant determinant of throwing performance
      such that high levels of speed and accuracy were achieved without a high degree
      of proprioception. There is no evidence to suggest therefore that this particular
      method of shoulder proprioception measurement should be implemented in clinical
      practice. Consequently, clinicians are encouraged to consider proprioception
      throughout the entire kinetic chain rather than the shoulder joint in isolation
      as a determining factor of performance in throwing athletes.

PMID- 24936899
TI  - Effects of G-trainer, cycle ergometry, and stretching on physiological and
      psychological recovery from endurance exercise.
AB  - The purpose of this study was to compare the effectiveness of 3 treatment modes
      (Anti-Gravity Treadmill [G-trainer], stationary cycling [CompuTrainer], and
      static stretching) on the physiological and psychological recovery after an acute
      bout of exhaustive exercise. In a crossover design, 12 aerobically trained men
      (21.3 +/- 2.3 years, 72.1 +/- 8.1 kg, 178.4 +/- 6.3 cm, (Equation is included in
      full-text article.): 53.7 +/- 6.3 ml.kg.min) completed a 29-km stationary cycling
      time trial. Immediately after the time trial, subjects completed 30 minutes of G
      trainer or CompuTrainer (40% (Equation is included in full-text article.)) or
      static stretching exercises. A significant time effect was detected for plasma
      lactate (p = 0.010) and serum cortisol (p = 0.039) after exercise. No treatment
      or treatment by time interaction was identified for lactate or cortisol,
      respectively. No main effects for time, treatment, or treatment by time
      interaction were identified for interleukin 6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha). No differences were observed among treatments in skeletal
      muscle peak power output, mean power output, time to peak power, and rate to
      fatigue at 24 hours postexercise bout. Finally, no significant changes in mood
      status were observed after exercise and between treatment groups. When compared
      with stationary cycling and static stretching, exercise recovery performed on the
      G-trainer was unable to reduce systemic markers of stress and inflammation, blood
      lactate, or improve anaerobic performance and psychological mood states after an
      exhaustive bout of endurance exercise. Further research is warranted that
      includes individualized recovery modalities to create balances between the
      stresses of training and competition.

PMID- 24936900
TI  - Physical and decision-making demands of Australian football umpires during
      competitive matches.
AB  - This study examined the physical and decision-making requirements of elite
      Australian football (AF) umpires during match play. Twenty-nine field umpires
      were assessed across 20 AF League matches. Physical demands were monitored using
      global positioning system devices to record the total distance covered and high
      speed running (HSR; >14.4 km.h) demands across each quarter. Decision-making
      performance was assessed through video by 3 elite umpire coaches who reviewed
      free-kick accuracy during each match. These data were further analyzed according
      to the position (mid-zone or end-zone) of the umpire when each decision was made.
      The average distance covered was 10,563 +/- 608 m, of which 1,952 +/- 494 m was
      HSR. Significant reductions in distance covered were observed during the third (p
      = 0.006) and fourth (p = 0.001) quarters, compared with the first. An average of
      44 +/- 8 free kicks awarded per match with a decision accuracy of 84 +/- 6%;
      however, there were no significant differences (p > 0.05) in these measures
      across a match. Significantly (p <= 0.05) higher physical (HSR; relative
      distance) and decision-making requirements were observed within the mid-zone. The
      current data quantify the physical and decision-making demands of AF umpiring and
      demonstrated that despite a high physical workload, free-kick accuracy is
      maintained across a match. This suggests that decision making may not be directly
      compromised by the intermittent running demands of AF umpires. Positional
      rotations between the mid-zone and end-zone position allow for the demands to be
      shared among all field umpires during a match.

PMID- 24936901
TI  - Effects of load on wingate test performances and reliability.
AB  - The purpose of this study was to examine the effects of 2 braking forces (8.7 and
      11% of body mass, BM) on Wingate test performance, peak lactate ([La]pk), peak
      heart rate (HRpk), and rate of perceived exertion (RPE). Sixteen male physical
      education students (age: 22.7 +/- 1.3 years, height: 1.81 +/- 0.07 m, BM: 74.3 +/
      9.6 kg) performed, in a randomized order, 2 Wingate tests at 8.7% BM and 2
      Wingate tests at 11% BM on a Monark cycle ergometer on 4 separate sessions. The
      results showed that the reliability level of mechanical measures was not affected
      by the braking force and was relatively similar for each variable in both braking
      forces (0.886 < ICC < 0.985). In addition, peak power, mean power, fatigue slope,
      and RPE were significantly higher (8.2, 7.0, 11.9, and 4.1%, respectively, all <
      0.05) using a braking force of 11% BM compared with 8.7% BM, whereas there was no
      significant effect of braking force on [La]pk and HRpk. In conclusion, the
      results of this study suggested that the reliability of the Wingate test does not
      depend on the used load, and a braking force of 11% BM is more optimal for power
      output during Wingate test in active adults.

PMID- 24936902
TI  - Progressive-overload whole-body vibration training as part of periodized, off
      season strength training in trained women athletes.
AB  - The purpose was to examine the effects of progressive-overload, whole-body
      vibration (WBV) training on strength and power as part of a 15-week periodized,
      strength training (ST) program. Eighteen collegiate women athletes with >=1 year
      of ST and no prior WBV training participated in the crossover design. Random
      assignment to 1 of the 2 groups followed pretests of seated medicine ball throw
      (SMBT), single-leg hop for distance (LSLH, RSLH), countermovement jump (CMJ), 3
      repetition maximum (3RM) front squat (FS), pull-up (PU), and 3RM bench press
      (BP). Whole-body vibration was two 3-week phases of dynamic and static hold body
      weight exercises administered 2 d.wk in ST sessions throughout the 15-week off
      season program. Total WBV exposure was 6 minutes broken into 30-second bouts with
      60-second rest (1:2 work-to-relief ratio). Exercises, frequency, and amplitude
      progressed in intensity from the first 3-week WBV training to the second 3-week
      phase. Repeated-measures analysis of variances were used to analyze the SMBT,
      CMJ, LSLH, RSLH, FS, PU, and BP tests. Alpha level was p <= 0.05. Front squat,
      LSLH, and RSLH increased (p = 0.001) from pre- to posttest; FS increased from mid
      to posttest. Pull-up increased (p = 0.008) from pre- to posttest. Seated
      medicine ball throw and BP showed a trend of increased performance from pre- to
      posttest (p = 0.11). Two 3-week phases of periodized, progressive-overload WBV +
      ST training elicited gains in strength and power during a 15-week off-season
      program. Greatest improvements in performance tests occurred in the initial WBV
      phase. Implementing WBV in conjunction with ST appears to be more effective in
      the early phases of training.

PMID- 24936903
TI  - Effects of BOSU ball(s) during sit-ups with body weight and added resistance on
      core muscle activation.
AB  - The objective of this study was to assess the electromyographic activity of the
      rectus abdominis (upper and lower part) and external oblique during sit-ups
      performed on BOSU ball(s). Twenty-four men participated in a familiarization
      session, and in the next session, they performed the experimental tests in
      randomized order. The sit-ups were performed with 10 repetitions with body weight
      and with 10 repetition maximum (10RM) using elastic bands as external resistance
      under 4 different conditions: (a) on a stable surface, (b) with the BOSU ball
      under their feet (dome side down, lower-body instability), (c) BOSU ball under
      the low back (dome side up, upper-body instability), and (d) with BOSU balls
      under both feet and the low back (dual instability). The feet were not attached
      to the surface. We observed that with body weight, external oblique activation
      was decreased by upper-body instability and dual instability by 22-24% (p = 0.002
      0.006), whereas the rectus abdominis was not affected by the surface. Using 10RM
      loads, the upper and lower rectus abdominis activities were increased by upper
      body and dual instability by 21-24% compared with that for a stable surface (P <=
      0.001-0.036). Further, lower-body instability did not affect muscle activities
      significantly with either load for any condition. Hence, BOSU balls under the low
      back can increase and decrease abdominal muscle activation depending on the load,
      whereas placing a BOSU ball under the feet with the dome side down had little
      impact.

PMID- 24936904
TI  - The effects of tapering on power-force-velocity profiling and jump performance in
      professional rugby league players.
AB  - The purpose of this study was to investigate the effects of a preseason taper on
      individual power-force-velocity profiles and jump performance in professional
      National Rugby League players. Seven professional rugby league players performed
      concentric squat jumps using ascending loads of 25, 50, 75, 100% body mass before
      and after a 21-day step taper leading into the in-season. Linear force-velocity
      relationships were derived, and the following variables were obtained: maximum
      theoretical velocity (V0), maximum theoretical force (F0), and maximum power
      (Pmax). The players showed likely-to-very likely increases in F0 (effect size
      [ES] = 0.45) and Pmax (ES = 0.85) from pre to posttaper. Loaded squat jump height
      also showed likely-to-most likely increases at each load (ES = 0.83-1.04). The 21
      day taper was effective at enhancing maximal power output and jump height
      performance in professional rugby players, possibly as a result of a recovery
      from fatigue and thus increased strength capability after a prolonged preseason
      training period. Rugby league strength and conditioning coaches should consider
      reducing training volume while maintaining intensity and aerobic conditioning
      (e.g., step taper) leading into the in-season.

PMID- 24936905
TI  - A simple video-based timing system for on-ice team testing in ice hockey: a
      technical report.
AB  - The purpose of this study was to describe and evaluate a newly developed on-ice
      timing system for team evaluation in the sport of ice hockey. We hypothesized
      that this new, simple, inexpensive, timing system would prove to be highly
      accurate and reliable. Six adult subjects (age 30.4 +/- 6.2 years) performed on
      ice tests of acceleration and conditioning. The performance times of the subjects
      were recorded using a handheld stopwatch, photocell, and high-speed (240 frames
      per second) video. These results were then compared to allow for accuracy
      calculations of the stopwatch and video as compared with filtered photocell
      timing that was used as the "gold standard." Accuracy was evaluated using maximal
      differences, typical error/coefficient of variation (CV), and intraclass
      correlation coefficients (ICCs) between the timing methods. The reliability of
      the video method was evaluated using the same variables in a test-retest analysis
      both within and between evaluators. The video timing method proved to be both
      highly accurate (ICC: 0.96-0.99 and CV: 0.1-0.6% as compared with the photocell
      method) and reliable (ICC and CV within and between evaluators: 0.99 and 0.08%,
      respectively). This video-based timing method provides a very rapid means of
      collecting a high volume of very accurate and reliable on-ice measures of skating
      speed and conditioning, and can easily be adapted to other testing surfaces and
      parameters.

PMID- 24936907
TI  - Shifts in the microbial community, nitrifiers and denitrifiers in the biofilm in
      a full-scale rotating biological contactor.
AB  - The objective of this study was to investigate the microbial community shifts,
      especially nitrifiers and denitrifiers, in the biofilm of two rotating biological
      contactor (RBC) trains with different running times along the plug flowpath. The
      microbial consortia were profiled using multiple approaches, including 454 high
      throughput sequencing of the V3-V4 region of 16S rRNA gene, clone libraries, and
      quantitative polymerase chain reaction (qPCR). The results demonstrated that (1)
      the overall microbial community at different locations had distinct patterns,
      that is, there were similar microbial communities at the beginnings of the two
      RBC trains and completely different populations at the ends of the two RBC
      trains; (2) nitrifiers, including ammonia-oxidizing archaea (AOA), ammonia
      oxidizing bacteria (AOB, Nitrosomonas) and nitrite-oxidizing bacteria (NOB,
      Nitrospira), increased in relative abundance in the biofilm along the flowpath,
      whereas denitrifiers (Rhodanobacter, Paracoccus, Thauera, and Azoarcus) markedly
      decreased; (3) the AOA were subdominant to the AOB in all sampled sections; and
      (4) strong ecological associations were shown among different bacteria. Overall,
      the results of this study provided more comprehensive information regarding the
      biofilm community composition and assemblies in full-scale RBCs. 

PMID- 24936906
TI  - Structure of local interactions in complex financial dynamics.
AB  - With the network methods and random matrix theory, we investigate the interaction
      structure of communities in financial markets. In particular, based on the random
      matrix decomposition, we clarify that the local interactions between the business
      sectors (subsectors) are mainly contained in the sector mode. In the sector mode,
      the average correlation inside the sectors is positive, while that between the
      sectors is negative. Further, we explore the time evolution of the interaction
      structure of the business sectors, and observe that the local interaction
      structure changes dramatically during a financial bubble or crisis. 

PMID- 24936908
TI  - Brightly luminescent Pt(II) pincer complexes with a sterically demanding
      carboranyl-phenylpyridine ligand: a new material class for diverse optoelectronic
      applications.
AB  - A series of three Pt(II) complexes with a doubly cyclometalating terdentate
      ligand L1, L1H2 = 3,6-bis(p-anizolyl)-2-carboranyl-pyridine, and diethyl sulfide
      (1), triphenylphosphine (2), and t-butylisonitrile (3) as ancillary ligands were
      synthesized. X-ray diffraction studies of 1 and 2 show a coordination of the L1
      ligand in a C-N-C mode in which the bulky and rigid o-carborane fragment is
      cyclometalated via a C atom. Importantly, no close intermolecular Pt-Pt contacts
      occur with this ligand type. The new Pt(II) pincer complexes display very high
      luminescence quantum yields at decay times of several tens of MUs even in
      solution under ambient conditions. On the basis of the low-temperature (T = 1.3
      K) emission decay behavior, the emission is assigned to a ligand centered triplet
      excited state (3)LC with small (1,3)MLCT admixtures. Because the phosphorescence
      is effectively quenched by molecular oxygen, optical sensors operating in a wide
      range of oxygen pressure can be developed. Owing to the very high luminescence
      quantum yields, the new materials might also become attractive as emitter
      materials for diverse optoelectronic applications. 

PMID- 24936909
TI  - Oxidative stress enhances the expression of sulfur assimilation genes:
      preliminary insights on the Enterococcus faecalis iron-sulfur cluster machinery
      regulation.
AB  - The Firmicutes bacteria participate extensively in virulence and pathological
      processes. Enterococcus faecalis is a commensal microorganism; however, it is
      also a pathogenic bacterium mainly associated with nosocomial infections in
      immunocompromised patients. Iron-sulfur [Fe-S] clusters are inorganic prosthetic
      groups involved in diverse biological processes, whose in vivo formation requires
      several specific protein machineries. Escherichia coli is one of the most
      frequently studied microorganisms regarding [Fe-S] cluster biogenesis and encodes
      the iron-sulfur cluster and sulfur assimilation systems. In Firmicutes species, a
      unique operon composed of the sufCDSUB genes is responsible for [Fe-S] cluster
      biogenesis. The aim of this study was to investigate the potential of the E.
      faecalis sufCDSUB system in the [Fe-S] cluster assembly using oxidative stress
      and iron depletion as adverse growth conditions. Quantitative real-time
      polymerase chain reaction demonstrated, for the first time, that Gram-positive
      bacteria possess an OxyR component responsive to oxidative stress conditions, as
      fully described for E. coli models. Likewise, strong expression of the sufCDSUB
      genes was observed in low concentrations of hydrogen peroxide, indicating that
      the lowest concentration of oxygen free radicals inside cells, known to be highly
      damaging to [Fe-S] clusters, is sufficient to trigger the transcriptional
      machinery for prompt replacement of [Fe-S] clusters. 

PMID- 24936911
TI  - Limits of a rapid identification of common Mediterranean sandflies using
      polymerase chain reaction-restriction fragment length polymorphism.
AB  - A total of 131 phlebotomine Algerian sandflies have been processed in the present
      study. They belong to the species Phlebotomus bergeroti, Phlebotomus alexandri,
      Phlebotomus sergenti, Phlebotomus chabaudi, Phlebotomus riouxi, Phlebotomus
      perniciosus, Phlebotomus longicuspis, Phlebotomus perfiliewi, Phlebotomus ariasi,
      Phlebotomus chadlii, Sergentomyia fallax, Sergentomyia minuta, Sergentomyia
      antennata, Sergentomyia schwetzi, Sergentomyia clydei, Sergentomyia christophersi
      and Grassomyia dreyfussi. They have been characterised by sequencing of a part of
      the cytochrome b (cyt b), t RNA serine and NADH1 on the one hand and of the
      cytochrome C oxidase I of the mitochondrial DNA (mtDNA) on the other hand. Our
      study highlights two sympatric populations within P. sergenti in the area of its
      type-locality and new haplotypes of P. perniciosus and P. longicuspis without
      recording the specimens called lcx previously found in North Africa. We tried to
      use a polymerase chain reaction-restriction fragment length polymorphism method
      based on a combined double digestion of each marker. These method is not
      interesting to identify sandflies all over the Mediterranean Basin. 

PMID- 24936912
TI  - Knockout confirmation for Hurries: rapid genotype identification of Trypanosoma
      cruzi transfectants by polymerase chain reaction directly from liquid culture.
AB  - Gene knockout is a widely used approach to evaluate loss-of-function phenotypes
      and it can be facilitated by the incorporation of a DNA cassette having a drug
      selectable marker. Confirmation of the correct knockout cassette insertion is an
      important step in gene removal validation and has generally been performed by
      polymerase chain reaction (PCR) assays following a time-consuming DNA extraction
      step. Here, we show a rapid procedure for the identification of Trypanosoma cruzi
      transfectants by PCR directly from liquid culture - without prior DNA extraction.
      This simple approach enabled us to generate PCR amplifications from different
      cultures varying from 106-108 cells/mL. We also show that it is possible to
      combine different primer pairs in a multiplex detection reaction and even to
      achieve knockout confirmation with an extremely simple interpretation of a real
      time PCR result. Using the "culture PCR" approach, we show for the first time
      that we can assess different DNA sequence combinations by PCR directly from
      liquid culture, saving time in several tasks for T. cruzi genotype interrogation.

PMID- 24936913
TI  - Progesterone.
AB  - Progestogens are a promising treatment in the prevention of spontaneous preterm
      birth in high-risk women. In women with a prior history of spontaneous preterm
      delivery and in women with a sonographic shortened cervix, there is considerable
      evidence supporting a benefit of progestogen therapy in the reduction of preterm
      delivery. In women with multifetal gestations, progestogen therapy has not been
      shown to be beneficial. Data are inconclusive in women with arrested preterm
      labor. Questions remain about the mechanism of progestogen action, the optimal
      type of progestogen, the best mode of administration, and the ideal dosing
      regimen. 

PMID- 24936914
TI  - The effect of maternal obesity on the offspring.
AB  - Maternal obesity is inextricably linked to adverse health outcomes for the mother
      and her children. The peripartum period is a critical period of risk. In this
      chapter, we examine the importance of maternal prepregnancy weight status,
      gestational weight gain, breastfeeding, and postpartum weight loss in relation to
      subsequent risk for maternal obesity and obesity in the offspring. Promoting
      optimal maternal weight during the preconception, pregnancy, and postpartum
      periods will provide lifelong benefits for maternal health and the health of her
      progeny. 

PMID- 24936915
TI  - Faculty development initiatives to advance research literacy and evidence-based
      practice at CAM academic institutions.
AB  - OBJECTIVES: To present the varied approaches of 9 complementary and alternative
      medicine (CAM) institutions (all grantees of the National Center for
      Complementary and Alternative Medicine) used to develop faculty expertise in
      research literacy and evidence-based practice (EBP) in order to integrate these
      concepts into CAM curricula. DESIGN: A survey to elicit information on the
      faculty development initiatives was administered via e-mail to the 9 program
      directors. All 9 completed the survey, and 8 grantees provided narrative
      summaries of faculty training outcomes. RESULTS: The grantees found the following
      strategies for implementing their programs most useful: assess needs, develop and
      adopt research literacy and EBP competencies, target early adopters and change
      leaders, employ best practices in teaching and education, provide meaningful
      incentives, capitalize on resources provided by grant partners, provide external
      training opportunities, and garner support from institutional leadership.
      Instructional approaches varied considerably across grantees. The most common
      were workshops, online resources, in-person short courses, and in-depth seminar
      series developed by the grantees. Many also sent faculty to intensive multiday
      extramural training programs. Program evaluation included measuring participation
      rates and satisfaction and the integration of research literacy and EBP learning
      objectives throughout the academic curricula. Most grantees measured longitudinal
      changes in beliefs, attitudes, opinions, and competencies with repeated faculty
      surveys. CONCLUSIONS: A common need across all 9 CAM grantee institutions was
      foundational training for faculty in research literacy and EBP. Therefore, each
      grantee institution developed and implemented a faculty development program. In
      developing the framework for their programs, grantees used strategies that were
      viewed critical for success, including making them multifaceted and unique to
      their specific institutional needs. These strategies, in conjunction with the
      grantees' instructional approaches, can be of practical use in other CAM and non
      CAM academic environments considering the introduction of research literacy and
      EBP competencies into their curricula.

PMID- 24936917
TI  - Untangling the triple low: causal inference in anesthesia research.

PMID- 24936918
TI  - Guaranteed by gas: Neiman's advertising bookmark.

PMID- 24936916
TI  - Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy.
AB  - One hundred years ago, Dr. Paul Ehrlich popularized the "magic bullet" concept
      for cancer therapy in which an ideal therapeutic agent would only kill the
      specific tumor cells it targeted. Since then, "targeted therapy" that
      specifically targets the molecular defects responsible for a patient's condition
      has become a long-standing goal for treating human disease. However, safe and
      efficient drug delivery during the treatment of cancer and infectious disease
      remains a major challenge for clinical translation and the development of new
      therapies. The advent of SELEX technology has inspired many groundbreaking
      studies that successfully adapted cell-specific aptamers for targeted delivery of
      active drug substances in both in vitro and in vivo models. By covalently linking
      or physically functionalizing the cell-specific aptamers with therapeutic agents,
      such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such
      as organic or inorganic nanocarriers, the targeted cells and tissues can be
      specifically recognized and the therapeutic compounds internalized, thereby
      improving the local concentration of the drug and its therapeutic efficacy.
      Currently, many cell-type-specific aptamers have been developed that can target
      distinct diseases or tissues in a cell-type-specific manner. In this review, we
      discuss recent advances in the use of cell-specific aptamers for targeted disease
      therapy, as well as conjugation strategies and challenges. 

PMID- 24936919
TI  - Ketamine metabolomics in the treatment of major depression.

PMID- 24936920
TI  - Cumulative duration of "triple low" state of low blood pressure, low bispectral
      index, and low minimum alveolar concentration of volatile anesthesia is not
      associated with increased mortality.
AB  - BACKGROUND: Mortality after noncardiac surgery has been associated with the
      "triple low state," a combination of low mean arterial blood pressure (<75 mmHg),
      low bispectral index (<45), and low minimum alveolar concentration of volatile
      anesthesia (<0.70). The authors set out to determine whether duration of a triple
      low state and aggregate risk associated with individual diagnostic and procedure
      codes are independently associated with perioperative and intermediate-term
      mortality. METHODS: The authors studied 16,263 patients (53 +/- 16 yr) who
      underwent noncardiac surgery at Duke University Medical Center between January
      2006 and December 2009. Multivariable logistic and Cox regression analyses were
      used to determine whether perioperative factors were independently associated
      with perioperative and intermediate-term all-cause mortality. RESULTS: The 30-day
      mortality rate was 0.8%. There were statistically significant associations
      between 30-day mortality and various perioperative risk factors including age,
      American Society of Anesthesiologists Physical Status, emergency surgery, higher
      Cleveland Clinic Risk Index score, and year of surgery. Cumulative duration of
      triple low state was not associated with 30-day mortality (multivariable odds
      ratio, 0.99; 95% CI, 0.92 to 1.07). The clinical risk factors for 30-day
      mortality remained predictors of intermediate-term mortality, whereas cumulative
      duration of triple low was not associated with intermediate-term mortality
      (multivariable hazard ratio, 0.98; 95% CI, 0.97 to 1.01). The multivariable
      logistic regression (c-index = 0.932) and Cox regression (c-index = 0.860) models
      showed excellent discriminative abilities. CONCLUSION: The authors found no
      association between cumulative duration of triple low state and perioperative or
      intermediate-term mortality in noncardiac surgery patients.

PMID- 24936921
TI  - "Hands-on" teaching by Chevalier Jackson.

PMID- 24936923
TI  - Wrenching experiences from the Heidbrink Company.

PMID- 24936922
TI  - (R,S)-Ketamine metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine
      increase the mammalian target of rapamycin function.
AB  - BACKGROUND: Subanesthetic doses of (R,S)-ketamine are used in the treatment of
      neuropathic pain and depression. In the rat, the antidepressant effects of (R,S)
      ketamine are associated with increased activity and function of mammalian target
      of rapamycin (mTOR); however, (R,S)-ketamine is extensively metabolized and the
      contribution of its metabolites to increased mTOR signaling is unknown. METHODS:
      Rats (n = 3 per time point) were given (R,S)-ketamine, (R,S)-norketamine, and
      (2S,6S)-hydroxynorketamine and their effect on the mTOR pathway determined after
      20, 30, and 60 min. PC-12 pheochromocytoma cells (n = 3 per experiment) were
      treated with escalating concentrations of each compound and the impact on the
      mTOR pathway was determined. RESULTS: The phosphorylation of mTOR and its
      downstream targets was significantly increased in rat prefrontal cortex tissue by
      more than ~2.5-, ~25-, and ~2-fold, respectively, in response to a 60-min
      postadministration of (R,S)-ketamine, (R,S)-norketamine, and (2S,6S)
      hydroxynorketamine (P < 0.05, ANOVA analysis). In PC-12 pheochromocytoma cells,
      the test compounds activated the mTOR pathway in a concentration-dependent
      manner, which resulted in a significantly higher expression of serine racemase
      with ~2-fold increases at 0.05 nM (2S,6S)-hydroxynorketamine, 10 nM (R,S)
      norketamine, and 1,000 nM (R,S)-ketamine. The potency of the effect reflected
      antagonistic activity of the test compounds at the alpha7-nicotinic acetylcholine
      receptor. CONCLUSIONS: The data demonstrate that (R,S)-norketamine and (2S,6S)
      hydroxynorketamine have potent pharmacological activity both in vitro and in vivo
      and contribute to the molecular effects produced by subanesthetic doses of (R,S)
      ketamine. The results suggest that the determination of the mechanisms underlying
      the antidepressant and analgesic effects of (R,S)-ketamine requires a full study
      of the parent compound and its metabolites.

PMID- 24936924
TI  - Factors affecting survival and neurologic outcome of patient with perioperative
      cardiac arrest.

PMID- 24936925
TI  - Data on the anesthetic procedure or surgical risk are still necessary.

PMID- 24936926
TI  - In reply.

PMID- 24936927
TI  - "Big data" has not come to pediatric anesthesia.

PMID- 24936928
TI  - In reply.

PMID- 24936933
TI  - Ketamine as an antidepresessant: a brief research history.

PMID- 24936934
TI  - Comprehensive chirality sensing: development of stereodynamic probes with a dual
      (chir)optical response.
AB  - The attachment of a salicylaldehyde ring and a cofacial aryl or heteroaryl N
      oxide chromophore onto a naphthalene scaffold affords stereodynamic probes
      designed to rapidly bind amines, amino alcohols, or amino acids and to translate
      this binding event via substrate-to-receptor chirality amplification into a dual
      (chir)optical response. 1-(3'-Formyl-4'-hydroxyphenyl)-8-(9'-anthryl)naphthalene
      (1) was prepared via two consecutive Suzuki cross-coupling reactions, and the
      three-dimensional structure and racemization kinetics were studied by
      crystallography and dynamic HPLC. This probe proved successful for chirality
      sensing of several compounds, but in situ IR monitoring of the condensation
      reaction between the salicylaldehyde moiety in 1 and phenylglycinol showed that
      the imine formation takes 2 h. Optimization of the substrate binding rate and the
      circular dichroism (CD) and fluorescence readouts led to the replacement of
      anthracene with smaller fluorophores capable of intramolecular hydrogen bonding.
      1-(3'-Formyl-4'-methoxyphenyl)-8-(4'-isoquinolyl)naphthalene N-oxide (2) and its
      pyridyl analogue 3 combine fast substrate binding with distinctive chiral
      amplification. This asymmetric transformation of the first kind prompts CD and
      fluorescence responses that can be used for in situ determination of the absolute
      configuration, ee, and total concentration of many compounds. The general utility
      of the three chemosensors was successfully tested on 18 substrates. 

PMID- 24936935
TI  - Direct formation of reduced graphene oxide and 3D lightweight nickel network
      composite foam by hydrohalic acids and its application for high-performance
      supercapacitors.
AB  - Here, a novel graphene composite foam with 3D lightweight continuous and
      interconnected nickel network was successfully synthesized by hydroiodic (HI)
      acid using nickel foam as substrate template. The graphene had closely coated on
      the backbone of the 3D nickel conductive network to form nickel network supported
      composite foam without any polymeric binder during the HI reduction of GO
      process, and the nickel conductive network can be maintained even in only a small
      amount of nickel with 1.1 mg/cm(2) and had replaced the traditional current
      collector nickel foam (35 mg/cm(2)). In the electrochemical measurement, a
      supercapacitor device based on the 3D nickel network and graphene composite foam
      exhibited high rate capability of 100 F/g at 0.5 A/g and 86.7 F/g at 62.5 A/g,
      good cycle stability with capacitance retention of 95% after 2000 cycles, low
      internal resistance (1.68 Omega), and excellent flexible properties. Furthermore,
      the gravimetric capacitance (calculated using the total mass of the electrode)
      was high up to 40.9 F/g. Our work not only demonstrates high-quality
      graphene/nickel composite foam, but also provides a universal route for the
      rational design of high performance of supercapacitors. 

PMID- 24936936
TI  - Sequential laser surgery for twin-twin transfusion syndrome.
AB  - Treatment of twin-twin transfusion syndrome (TTTS) via the sequential selective
      laser photocoagulation of communicating vessels (SQLPCV) technique involves
      lasering the arteriovenous communications from the donor twin to the recipient
      twin first, followed by the arteriovenous communications from the recipient twin
      to the donor. Occluding the vascular communications in this particular order may
      result in transient intraoperative net transfusion to the donor twin and
      facilitate hemodynamic equilibrium, particularly to the volume depleted donor
      twin. Preliminary evidence suggests that the SQLPCV technique may result in
      improved perinatal outcomes compared with the standard selective (SLPCV) laser
      surgical approach. In this article, we describe the pathophysiological basis for
      this surgical approach, delineate the surgical technique, review the literature,
      and elaborate on the outstanding questions of the SQLPCV treatment of TTTS. 

PMID- 24936938
TI  - Socioeconomic disparities in diagnostic testing after positive aneuploidy
      screening.
AB  - OBJECTIVE: The objective of this study was to investigate the association between
      type of health insurance (Medicaid vs. private) and uptake of diagnostic testing
      for fetal aneuploidy after a positive screening test result. METHODS: We
      performed a retrospective cohort study of pregnant women who underwent aneuploidy
      screening in the first and/or second trimesters of pregnancy and received
      positive results. The characteristics of and outcomes for women with Medicaid
      were compared with those of women with private insurance in both univariable and
      multivariable analyses. RESULTS: In this study, 75 women with Medicaid and 75
      with private insurance were analyzed. Those with Medicaid were younger (33.8 vs.
      36.9 years, p < 0.01), and more likely to be of non-white race/ethnicity (88 vs.
      27%, p < 0.01), unmarried (65 vs. 19%, p < 0.01), non-English speaking (12 vs.
      0%, p < 0.01), and multiparous (76 vs. 59%, p = 0.02). They also were less likely
      to undergo diagnostic testing after a positive aneuploidy screen (35 vs. 57%, p <
      0.01). In multivariable analysis, those with Medicaid remained significantly less
      likely to undergo diagnostic testing (odds ratio, 0.26; 95% confidence interval,
      0.09-0.80). CONCLUSION: Women with Medicaid are less likely than women with
      private insurance to undergo diagnostic testing after positive screening for
      aneuploidy. These results emphasize the potential importance of improved
      counseling for low-income women.

PMID- 24936939
TI  - Electronic dynamics by ultrafast pump photoelectron detachment probed by
      ionization: a dynamical simulation of negative-neutral-positive in LiH(-).
AB  - The control of electronic dynamics in the neutral electronic states of LiH before
      the onset of significant nuclei motion is investigated using a negative-neutral
      positive (NeNePo) ultrafast IR pump-attoescond pulse train (APT) probe scheme.
      Starting from the ground state of the anion (LiH(-)), multiphoton ultrafast
      electron detachment and subsequent excitation of the neutral by a few femtosecond
      intense IR pulse produces a non-equilibrium electronic density in neutral LiH.
      The coherent electronic wave packet is then probed by angularly resolved
      photoionization to the cation by an APT generated from a replica of the pump IR
      pulse at several time delays. Realistic parameters for the pump and the APT are
      used. Several NeNePo schemes are simulated using different IR carrier
      frequencies, showing that the delay between the successive attosecond pulses in
      the train can be used as a filter to probe the different pairs of states present
      in the coherent electronic wave packet produced by the pump pulse. The dynamical
      simulations include the pump and the probe pulses to all orders by solving the
      time-dependent Schrodinger equation using a coupled equation scheme for the
      manifolds of the anion, neutral, and cation subspaces. We show that an incomplete
      molecular orientation of the molecule in the laboratory frame does not prevent
      probing the electronic density localization by angularly resolved photoelectron
      maps. 

PMID- 24936937
TI  - The association of cord serum cytokines with neurodevelopmental outcomes.
AB  - OBJECTIVE: To test whether elevated umbilical cord serum inflammatory cytokine
      levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay
      (NDD). STUDY DESIGN: Nested case-control analysis within a clinical trial of
      antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for
      prevention of CP, with evaluation of surviving children at the age of 2. NDD was
      defined as a Bayley psychomotor developmental index (PDI) and/or mental
      developmental index (MDI) < 70. Controls, defined as surviving children without
      CP and with Bayley PDI and MDI >= 85, were matched by race and gestational age.
      Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1beta),
      and tumor necrosis factor-alpha (TNF-alpha) levels. Elevated cytokine levels were
      defined as >= 75th percentile in placebo-exposed controls. Analyses compared
      case/control cytokine levels, adjusting for MgSO4 exposure, gestational age,
      race/ethnicity, and sociodemographic differences. RESULTS: Logistic regression
      analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1beta
      were more common in cord blood serum from infants with subsequent low MDI as
      compared with controls. After adjusting for additional confounders, the
      significant differences were no longer evident. Cytokine levels (IL-8, IL-1beta,
      and TNF-alpha) were not elevated with CP or low PDI. CONCLUSION: Cord serum IL-8,
      IL-1beta, and TNF-alpha levels in preterm infants are not associated with
      subsequent CP or NDD.

PMID- 24936940
TI  - Myelinated nerve fiber-associated local scleral excavation and induced axial
      myopia.
AB  - PURPOSE: To investigate the association between the distributions of local
      scleral excavation and myelinated nerve fibers (MNF) and to elucidate the
      pathogenic mechanism of axial myopia in eyes with MNF. METHODS: In six eyes of
      six pediatric patients with MNF, the distribution of the MNF on fundus
      photography was compared with the regional excavation of the sclera on linear
      scans across the fovea and a peripapillary circular scan of spectral domain
      optical coherence tomography. RESULTS: The tilting of Bruch membrane on vertical
      scan of spectral domain optical coherence tomography was associated with the
      major distribution of MNF (kappa = 1, Cohen's kappa coefficient). The area of MNF
      of 12 clock-hour segments and focal scleral excavation on circular scan of
      spectral domain optical coherence tomography were significantly correlated (P <
      0.001, generalized estimating equation). The deepest direction of the circular
      scan was correlated with the direction of MNF vector defined as the average of
      the MNF direction weighted by the MNF area along 12 clock-hour segment (P <
      0.036, Spearman correlation test). CONCLUSION: Localized scleral excavation was
      strongly associated with the distribution of the MNF. This result indicates that
      the retinal areas deprived of visual stimulation by the MNF contribute to the
      development of axial myopia through local effects on the underlying sclera in
      early life.

PMID- 24936941
TI  - Outcomes of anti-vascular endothelial growth factor therapy in the management of
      choroidal neovascularization associated with choroidal osteoma.
AB  - PURPOSE: To investigate the efficacy of serial anti-vascular endothelial growth
      factor injections for choroidal neovascularization associated with choroidal
      osteoma. METHODS: In this retrospective interventional case series, eyes with
      choroidal osteoma and associated choroidal neovascularization were treated with
      intravitreal ranibizumab or bevacizumab with or without photodynamic therapy
      consolidation. Resolution of subretinal fluid on optical coherence tomography and
      best-corrected visual acuity were assessed. RESULTS: Eight eyes in eight patients
      were treated with monthly intravitreal anti-vascular endothelial growth factor
      injections with or without photodynamic therapy. Resolution of subretinal fluid
      on optical coherence tomography was achieved in 7 of 8 eyes (87%) with a mean of
      12.3 +/- 12.6 injections (range, 1-40). Four eyes (50%) experienced at least 1
      recurrence of exudation at a mean interval of 10 months (median, 7.5; range, 5-21
      months), necessitating further therapy. The mean Snellen visual acuity
      improvement was 1 +/- 4 lines (range, loss 3 to gain 7 lines) at a mean of 32
      months follow-up. CONCLUSION: Serial anti-vascular endothelial growth factor
      therapy alone or with photodynamic therapy consolidation for choroidal
      neovascularization due to choroidal osteoma resulted in anatomical improvement
      and modest visual gain.

PMID- 24936942
TI  - Fibrovascular pigment epithelial detachment is a risk factor for long-term visual
      decay in neovascular age-related macular degeneretion.
AB  - BACKGROUND: The individual outcome of anti-vascular endothelial growth factor
      treatment in neovascular age-related macular degeneration is variable. To
      investigate the prognostic value of spectral domain optical coherence tomography
      structures for best-corrected visual acuity (BCVA) outcome, volumetric analysis
      of spectral domain optical coherence tomography structures was performed in
      neovascular age-related macular degeneration correlated with BCVA after 24
      months. METHODS: At the Department of Ophthalmology, University of Cologne,
      Germany, 75 patients with neovascular age-related macular degeneration were
      analyzed prospectively over 24 months. Patients received three initial
      consecutive monthly intravitreal ranibizumab injections followed by monthly
      spectral domain optical coherence tomography controls. Therapy was continued as a
      pro re nata regimen. Volumetric analysis of spectral domain optical coherence
      tomography images was performed using commercially available software (3D
      Doctor). RESULTS: Subretinal tissue, subretinal fluid, serous pigment epithelial
      detachment, and fibrovascular pigment epithelial detachment (FPED) were
      identified. By contrast to all other structures, FPED did not respond to
      ranibizumab therapy. Volume of FPED at baseline and after the loading phase
      correlated most with impaired BCVA after 24 months (r = -0.0215, P = 0.9263
      [subretinal tissue]; r = -0.3120, P = 0.0216 [subretinal fluid]; r = -0.0757, P =
      0.6470 [serous pigment epithelial detachment]; r = -0.4182, P = 0.0111 (FPED
      baseline); r = -0.4768; P = 0.0002 [FPED after loading phase]). CONCLUSION: Of
      all identified structures, FPED was most deleterious for BCVA after 24 months.
      The knowledge about possible BCVA course can influence the decision for more
      intense treatment regimens.

PMID- 24936943
TI  - Choroidal thickness after intraarterial chemotherapy for retinoblastoma.
AB  - PURPOSE: To measure the choroidal thickness (CT) and analyze the morphologic
      features of chorioretinal structures using a portable handheld spectral domain
      optical coherence tomography in patients with retinoblastoma after intraarterial
      chemotherapy. METHODS: This was a case-control study. Eighteen eyes of 9 patients
      with unilateral retinoblastoma treated with intraarterial chemotherapy were
      assessed by spectral-domain optical coherence tomography. Submacular CT was
      measured at the foveola and at points located 500 MUm and 2 mm from the foveola.
      The treated eye was compared with the untreated (control) eye. RESULTS: Mean
      submacular CT was 174 +/- 111.1 MUm in the treated eyes and 259 +/- 42.2 MUm in
      the control eyes (P = 0.054). Several point locations showed statistically
      significant differences comparing CT (treated eye vs. control eye), including
      subfoveolar (P = 0.030), nasal 0.5 mm (P = 0.037), nasal 2 mm (P = 0.049), and
      temporal 2 mm (P = 0.031). In 4 patients with ophthalmoscopically visible
      choroidal atrophy, submacular CT was reduced by 73.3 +/- 14.1% compared with the
      control eye. In 5 patients with no ophthalmoscopically visible choroidal atrophy,
      submacular CT was reduced by 0.5 +/- 11.9% compared with the control eye.
      CONCLUSION: Intraarterial chemotherapy for retinoblastoma can cause reduction in
      subfoveolar CT. Spectral-domain optical coherence tomography confirmed choroid to
      be thinned in eyes with or without clinical evidence of choroidal atrophy.

PMID- 24936944
TI  - Ocular findings at initial pan retinal photocoagulation for proliferative
      diabetic retinopathy predict the need for future pars plana vitrectomy.
AB  - PURPOSE: To determine the 1-year and 2-year likelihood of vitrectomy in diabetic
      patients undergoing initial pan retinal photocoagulation (PRP). METHODS: Diabetic
      eyes receiving initial PRP for proliferative diabetic retinopathy (PDR) were
      analyzed to determine their risk for vitrectomy based on clinical findings.
      RESULTS: In total, 374 eyes of 272 patients were analyzed. The percentage of eyes
      undergoing vitrectomy 1 year and 2 years following initial PRP was 19.1% and
      26.2%, respectively. Of the eyes in Group 1 (PDR alone), Group 2 (PDR and
      vitreous hemorrhage), and Group 3 (PDR and iris neovascularization, vitreous
      hemorrhage with traction or fibrosis, or fibrosis alone), the percentage
      receiving pars plana vitrectomy at 1 year and 2 years was 9.73% (18/185) and
      15.7% (29/185), 26.9% (43/160) and 34.4% (55/160), and 37.9% (11/29) and 48.3%
      (14/29), respectively. Eyes in Group 2 had 2.78 times greater likelihood (P <
      0.0001) and eyes in Group 3 had 3.54 times higher likelihood (P < 0.0001) of
      requiring pars plana vitrectomy within 2 years than those with PDR alone.
      CONCLUSION: Eyes receiving PRP for PDR with associated hemorrhage or traction
      were more likely to undergo pars plana vitrectomy within 1 year and 2 years
      following initial PRP compared with eyes with only PDR, providing important
      prognostic information for PRP-naive patients.

PMID- 24936945
TI  - Optical properties of single plasmonic holes probed with local electron beam
      excitation.
AB  - Similar to nanoparticles, nanoscale holes form a basic building block in a wide
      array of nanophotonic devices. Here we study the spectral and angular
      cathodoluminescence response of individual nanoholes with diameters ranging from
      50 to 180 nm. Taking advantage of the deep-subwavelength excitation resolution,
      we find that the holes can be excited efficiently at the edge of the hole and
      that the response becomes stronger in the near-infrared part of the spectrum for
      larger holes. Using finite-difference time-domain simulations, we characterize
      the resonant modes inside the holes. We measure the angle-resolved
      cathodoluminescence response and observe strong beaming toward the side of
      electron beam excitation, complementary to what was shown for nanoparticles. The
      angular response can be explained by assuming a coherent superposition of
      radiating dipole moments, where the contribution of in-plane magnetic and
      electric dipole components increases for larger diameters. 

PMID- 24936946
TI  - A framework for a context-aware elderly entertainment support system.
AB  - Elderly people constitute a major portion of world's population. Many of them are
      physically and mentally vulnerable and need continuous support for their health
      and well-being. There is a growing trend that these elderly people are placed in
      an ambient assisted living environment (AAL) with an aim to receive better care
      and support. In such settings, a lot of attention has been given to continuous
      health monitoring for maintaining physical health status. However, much less
      attention has been given toward understanding the entertainment needs of the
      elderly people, which is an important factor relevant to their mental health and
      joyful living. This paper thus addresses the entertainment needs of the elderly
      and proposes a framework of an elderly entertainment support system. The proposed
      framework enables different categories of residents (e.g., elderly people and
      caregivers) to access various media services in both implicit and explicit manner
      in order to enhance the quality of their living experience in different contexts.
      Our experimental results demonstrate the viability of the proposed framework. We
      believe that the proposed approach will establish the need to develop
      entertainment systems and services for the elderly people and allow us to
      sensibly address the problems associated with their independent, happy and active
      living. 

PMID- 24936947
TI  - Diffusion maps for multimodal registration.
AB  - Multimodal image registration is a difficult task, due to the significant
      intensity variations between the images. A common approach is to use
      sophisticated similarity measures, such as mutual information, that are robust to
      those intensity variations. However, these similarity measures are
      computationally expensive and, moreover, often fail to capture the geometry and
      the associated dynamics linked with the images. Another approach is the
      transformation of the images into a common space where modalities can be directly
      compared. Within this approach, we propose to register multimodal images by using
      diffusion maps to describe the geometric and spectral properties of the data.
      Through diffusion maps, the multimodal data is transformed into a new set of
      canonical coordinates that reflect its geometry uniformly across modalities, so
      that meaningful correspondences can be established between them. Images in this
      new representation can then be registered using a simple Euclidean distance as a
      similarity measure. Registration accuracy was evaluated on both real and
      simulated brain images with known ground-truth for both rigid and non-rigid
      registration. Results showed that the proposed approach achieved higher accuracy
      than the conventional approach using mutual information. 

PMID- 24936948
TI  - Railway crossing risk area detection using linear regression and terrain drop
      compensation techniques.
AB  - Most railway accidents happen at railway crossings. Therefore, how to detect
      humans or objects present in the risk area of a railway crossing and thus prevent
      accidents are important tasks. In this paper, three strategies are used to detect
      the risk area of a railway crossing: (1) we use a terrain drop compensation (TDC)
      technique to solve the problem of the concavity of railway crossings; (2) we use
      a linear regression technique to predict the position and length of an object
      from image processing; (3) we have developed a novel strategy called calculating
      local maximum Y-coordinate object points (CLMYOP) to obtain the ground points of
      the object. In addition, image preprocessing is also applied to filter out the
      noise and successfully improve the object detection. From the experimental
      results, it is demonstrated that our scheme is an effective and corrective method
      for the detection of railway crossing risk areas. 

PMID- 24936949
TI  - Vibration sensor-based bearing fault diagnosis using ellipsoid-ARTMAP and
      differential evolution algorithms.
AB  - Effective fault classification of rolling element bearings provides an important
      basis for ensuring safe operation of rotating machinery. In this paper, a novel
      vibration sensor-based fault diagnosis method using an Ellipsoid-ARTMAP network
      (EAM) and a differential evolution (DE) algorithm is proposed. The original
      features are firstly extracted from vibration signals based on wavelet packet
      decomposition. Then, a minimum-redundancy maximum-relevancy algorithm is
      introduced to select the most prominent features so as to decrease feature
      dimensions. Finally, a DE-based EAM (DE-EAM) classifier is constructed to realize
      the fault diagnosis. The major characteristic of EAM is that the sample
      distribution of each category is realized by using a hyper-ellipsoid node and
      smoothing operation algorithm. Therefore, it can depict the decision boundary of
      disperse samples accurately and effectively avoid over-fitting phenomena. To
      optimize EAM network parameters, the DE algorithm is presented and two
      objectives, including both classification accuracy and nodes number, are
      simultaneously introduced as the fitness functions. Meanwhile, an exponential
      criterion is proposed to realize final selection of the optimal parameters. To
      prove the effectiveness of the proposed method, the vibration signals of four
      types of rolling element bearings under different loads were collected. Moreover,
      to improve the robustness of the classifier evaluation, a two-fold cross
      validation scheme is adopted and the order of feature samples is randomly
      arranged ten times within each fold. The results show that DE-EAM classifier can
      recognize the fault categories of the rolling element bearings reliably and
      accurately. 

PMID- 24936950
TI  - Electrochemical mechanism of ion current rectification of polyelectrolyte gel
      diodes.
AB  - Polyelectrolyte gel diodes that are double layers of two oppositely charged
      polyelectrolyte gels, sandwiched by two symmetric electrodes, are emergent ionic
      devices. These diodes are designed to rectify ion currents with a physical
      mechanism that is analogous to conventional semiconductor diodes-the asymmetry in
      the permeability of ions across the interfaces between the two oppositely charged
      gels. Here we show that polyelectrolyte gel diodes indeed rectify steady currents
      with a physical mechanism that is very different from conventional diodes by
      using a simple electrochemical model; electric currents are limited by
      electrochemical reactions that are driven by potential drops at electrodes and
      these potential drops markedly change with changing the direction of applied
      voltages due to the redistribution of non-reactive counterions, leading to
      rectified ion currents. This concept is relatively generic and thus may provide
      insight in the physics of analogous ionic and biomimetic systems that show
      electrochemical reactions. 

PMID- 24936952
TI  - PIN architecture for ultrasensitive organic thin film photoconductors.
AB  - Organic thin film photoconductors (OTFPs) are expected to have wide applications
      in the field of optical communications, artificial vision and biomedical sensing
      due to their great advantages of high flexibility and low-cost large-area
      fabrication. However, their performances are not satisfactory at present: the
      value of responsivity (R), the parameter that measures the sensitivity of a
      photoconductor to light, is below 1 AW(-1). We believe such poor performance is
      resulted from an intrinsic self-limited effect of present bare blend based device
      structure. Here we designed a PIN architecture for OTFPs, the PIN device exhibits
      a significantly improved high R value of 96.5 AW(-1). The PIN architecture and
      the performance the PIN device shows here should represent an important step in
      the development of OTFPs.

PMID- 24936954
TI  - Effects of self-referencing on feeling-of-knowing accuracy and recollective
      experience.
AB  - The current research investigated the impact of self-referencing (SR) on feeling
      of-knowing (FOK) judgements to improve our understanding of the mechanisms
      underlying these metamemory judgements and specifically test the relationship
      between recollective experiences and FOK accuracy within the accessibility
      framework FOK judgements are thought to be by-products of the retrieval process
      and are therefore closely related to memory performance. Because relating
      information to one's self is one of the factors enhancing memory performance, we
      investigated the effect of self-related encoding on FOK accuracy and recollective
      experience. We compared performance on this condition to a separate deep
      processing condition in which participants reported the frequency of occurrence
      of pairs of words. Participants encoded pairs of words incidentally, and
      following a delay interval, they attempted at retrieving each target prompted by
      its cue. Then, they were re-presented with all cues and asked to provide FOK
      ratings regarding their likelihood of recognising the targets amongst
      distractors. Finally, they were given a surprise recognition task in which
      following each response they identified whether the response was remembered,
      known or just guessed. Our results showed that only SR at encoding resulted in
      better memory, higher FOK accuracy and increased recollective experience. 

PMID- 24936953
TI  - Targeting the androgen receptor with steroid conjugates.
AB  - The androgen receptor (AR) is a major therapeutic target in prostate cancer
      pharmacology. Progression of prostate cancer has been linked to elevated
      expression of AR in malignant tissue, suggesting that AR plays a central role in
      prostate cancer cell biology. Potent therapeutic agents can be precisely crafted
      to specifically target AR, potentially averting systemic toxicities associated
      with nonspecific chemotherapies. In this review, we describe various strategies
      to generate steroid conjugates that can selectively engage AR with high potency.
      Analogies to recent developments in nonsteroidal conjugates targeting AR are also
      evaluated. Particular focus is placed on potential applications in AR
      pharmacology. The review culminates with a description of future prospects for
      targeting AR. 

PMID- 24936955
TI  - Parity and pancreatic cancer risk: evidence from a meta-analysis of twenty
      epidemiologic studies.
AB  - Multiple studies have hypothesized parity is associated with pancreatic cancer
      risk but obtained conflicting results. We conducted a meta-analysis (including a
      dose-response approach) of current available epidemiologic studies to investigate
      the association between parity and risk of pancreatic cancer. Ten cohort studies
      and ten case-control studies including 8205 cases were eligible for inclusion.
      The combined RR (relative risk) of pancreatic cancer for the parous vs.
      nulliparous was 0.91 (95% CI, confidence interval = 0.85-0.97, I(2) = 39.0%, P(h)
      = 0.01). We observed an inverse association between giving birth to two children
      pancreatic cancer risk with RR of 0.86 (95% CI = 0.80-0.93, I(2) = 8.7%, P(h) =
      0.36). And no evidence supported there was non-linear (P = 0.33) or linear
      relationship (P = 0.14) between number of parity and risk of pancreatic cancer.
      Findings from this meta-analysis indicate that giving birth to two children has
      the lowest pancreatic cancer risk, mechanism of this protective effect needs
      further investigation.

PMID- 24936956
TI  - Influence of image slice thickness on rectal dose-response relationships
      following radiotherapy of prostate cancer.
AB  - When pooling retrospective data from different cohorts, slice thicknesses of
      acquired computed tomography (CT) images used for treatment planning may vary
      between cohorts. It is, however, not known if varying slice thickness influences
      derived dose-response relationships. We investigated this for rectal bleeding
      using dose-volume histograms (DVHs) of the rectum and rectal wall for dose
      distributions superimposed on images with varying CT slice thicknesses. We used
      dose and endpoint data from two prostate cancer cohorts treated with three
      dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159)
      at 2 Gy per fraction. The rectum was defined as the whole organ with content, and
      the morbidity cut-off was Grade >=2 late rectal bleeding. Rectal walls were
      defined as 3 mm inner margins added to the rectum. DVHs for simulated slice
      thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired
      slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed
      from the DVHs, and generalized equivalent uniform dose (gEUD) values were
      calculated. For each organ and each of the simulated slice thicknesses, we
      performed predictive modeling of late rectal bleeding using the Lyman-Kutcher
      Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased
      (<=18%), whereas maximum and mean doses decreased (<=0.8 and <=4.2 Gy,
      respectively). For all a values, the gEUD for the simulated DVHs were <=1.9 Gy
      different than the gEUD for the original DVHs. The best-fitting LKB model
      parameter values with 95% CIs were consistent between all DVHs. In conclusion, we
      found that the investigated slice thickness variations had minimal impact on
      rectal dose-response estimations. From the perspective of predictive modeling,
      our results suggest that variations within 10 mm in slice thickness between
      cohorts are unlikely to be a limiting factor when pooling multi-institutional
      rectal dose data that include slice thickness variations within this range. 

PMID- 24936957
TI  - Protein delivery using Cys2-His2 zinc-finger domains.
AB  - The development of new methods for delivering proteins into cells is a central
      challenge for advancing both basic research and therapeutic applications. We
      previously reported that zinc-finger nuclease proteins are intrinsically cell
      permeable due to the cell-penetrating activity of the Cys2-His2 zinc-finger
      domain. Here, we demonstrate that genetically fused zinc-finger motifs can
      transport proteins and enzymes into a wide range of primary and transformed
      mammalian cell types. We show that zinc-finger domains mediate protein uptake at
      efficiencies that exceed conventional protein transduction systems and do so
      without compromising enzyme activity. In addition, we demonstrate that zinc
      finger proteins enter cells primarily through macropinocytosis and facilitate
      high levels of cytosolic delivery. These findings establish zinc-finger proteins
      as not only useful tools for targeted genome engineering but also effective
      reagents for protein delivery. 

PMID- 24936959
TI  - Cytotoxic coumarins from Toddalia asiatica.
AB  - Three new coumarins and 13 known compounds were isolated from the stem bark of
      Toddalia asiatica. Compounds 1, 3, 8, and 9 showed cytotoxicity against the NCI
      H187 cell line with IC50 values ranging from 6 to 9 ug/mL. Compounds 4 and 9
      exhibited cytotoxicity against the MCF-7 cell line with IC50 values of 3.17 and
      9.79 ug/mL, respectively. Compound 9 also displayed cytotoxic activity against KB
      cells with an IC50 value of 8.63 ug/mL. In addition, compound 14 showed
      antimalarial activity against Plasmodium falciparum with an IC50 value of 3.66
      ug/mL. Compounds 5, 9, and 16 exhibited antituberculosis activity against
      Mycobacterium tuberculosis with MIC values of 50, 50, and 25 ug/mL, respectively.

PMID- 24936960
TI  - Thermally activated delayed fluorescence of fluorescein derivative for time
      resolved and confocal fluorescence imaging.
AB  - Compared with fluorescence imaging utilizing fluorophores whose lifetimes are in
      the order of nanoseconds, time-resolved fluorescence microscopy has more
      advantages in monitoring target fluorescence. In this work, compound DCF-MPYM,
      which is based on a fluorescein derivative, showed long-lived luminescence (22.11
      MUs in deaerated ethanol) and was used in time-resolved fluorescence imaging in
      living cells. Both nanosecond time-resolved transient difference absorption
      spectra and time-correlated single-photon counting (TCSPC) were employed to
      explain the long lifetime of the compound, which is rare in pure organic
      fluorophores without rare earth metals and heavy atoms. A mechanism of thermally
      activated delayed fluorescence (TADF) that considers the long wavelength
      fluorescence, large Stokes shift, and long-lived triplet state of DCF-MPYM was
      proposed. The energy gap (DeltaEST) of DCF-MPYM between the singlet and triplet
      state was determined to be 28.36 meV by the decay rate of DF as a function of
      temperature. The DeltaE(ST) was small enough to allow efficient intersystem
      crossing (ISC) and reverse ISC, leading to efficient TADF at room temperature.
      The straightforward synthesis of DCF-MPYM and wide availability of its starting
      materials contribute to the excellent potential of the compound to replace
      luminescent lanthanide complexes in future time-resolved imaging technologies.

PMID- 24936961
TI  - A state-of-the-art review on the evolution of urinary sphincter devices for the
      treatment of post-prostatectomy urinary incontinence: past, present and future
      innovations.
AB  - An artificial urinary sphincter (AUS) is the only mechanical device that closely
      simulates the function of a biological urinary sphincter. Over the past four
      decades, advances in mechanical design, applications of new technology and
      lessons learned from clinical experience have made AMS 800 device the standard of
      care in post-prostatectomy urinary incontinence. While the current AMS 800 device
      provides an effective, safe and durable option, it is not without its limitations
      and complications. Newer and innovative AUS-like devices are designed to rectify
      some of AMS 800 device problems, but, like any mechanical device, they too have
      their own shortcomings. Emerging novel therapies such as nanotechnology-driven
      device and stem cell therapy are attractive, but are not commercially available
      or have no proven long-term outcome. The following article provides a critical
      review on the past, present and future innovations in designing the ideal urinary
      sphincter to treat post-prostatectomy urinary incontinence.

PMID- 24936962
TI  - A novel method to estimate changes in stress-induced salivary alpha-amylase using
      heart rate variability and respiratory rate, as measured in a non-contact manner
      using a single radar attached to the back of a chair.
AB  - The authors have developed a non-contact system which estimates changes in
      salivary alpha-amylase (sAA ratio) induced by stress. Before and after stressful
      sound exposure, a single 24 GHz compact radar which is attached to the back of a
      chair measures the low frequency (LF) component of heart rate variability and
      respiratory rate, alpha-amylase in the subjects' buccal secretions was measured
      by using an alpha-amylase assay kit. Using multiple regression analysis, sAA
      ratio was estimated using stress-induced LF change (LF ratio) and stress-induced
      respiratory rate change (respiratory rate ratio). Twelve healthy subjects were
      tested (12 males, 22 +/- 2 years), who were exposed to audio stimuli with a
      composite tone of 2120 Hz and 2130 Hz sine waves at a sound pressure level of 95
      dB after a silent period through a headphone. The result showed that sAA ratio
      estimated using multiple regression analysis significantly correlated with
      measured sAA ratio (R = 0.76, p < 0.01). This indicates that the system may serve
      for a stress management in the future.

PMID- 24936963
TI  - A new approach based on the median filter to T-wave detection in ECG signal.
AB  - The electrocardiogram (ECG) is one of the most used signals in the diagnosis of
      heart disease. It contains different waves which directly correlate to heart
      activity. Different methods have been used in order to detect these waves and
      consequently lead to heart activity diagnosis. This paper is interested more
      particularly to the detection of the T-wave. Such a wave represents the re
      polarization state of the heart activity. The proposed approach is based on the
      algorithm procedure which allows the detection of the T-wave using a lot of
      filter including mean and median filter. The proposed algorithm is implemented
      and tested on a set of ECG recordings taken from, respectively, the European STT,
      MITBIH and MITBIH ST databases. The results are found to be very satisfactory in
      terms of sensitivity, predictivity and error compared to other works in the
      field.

PMID- 24936965
TI  - Physiotherapy for Parkinson's disease: a comparison of techniques.
AB  - BACKGROUND: Despite medical therapies and surgical interventions for Parkinson's
      disease (PD), patients develop progressive disability. The role of physiotherapy
      is to maximise functional ability and minimise secondary complications through
      movement rehabilitation within a context of education and support for the whole
      person. The overall aim is to optimise independence, safety and wellbeing,
      thereby enhancing quality of life. Trials have shown that physiotherapy has short
      term benefits in PD. However, which physiotherapy intervention is most effective
      remains unclear. OBJECTIVES: To assess the effectiveness of one physiotherapy
      intervention compared with a second approach in patients with PD. SEARCH METHODS:
      Relevant trials were identified by electronic searches of numerous literature
      databases (for example MEDLINE, EMBASE) and trial registers, plus handsearching
      of major journals, abstract books, conference proceedings and reference lists of
      retrieved publications. The literature search included trials published up to the
      end of January 2012. SELECTION CRITERIA: Randomised controlled trials of one
      physiotherapy intervention versus another physiotherapy intervention in patients
      with PD. DATA COLLECTION AND ANALYSIS: Data were abstracted independently from
      each paper by two authors. Trials were classified into the following intervention
      comparisons: general physiotherapy, exercise, treadmill training, cueing, dance
      and martial arts. MAIN RESULTS: A total of 43 trials were identified with 1673
      participants. All trials used small patient numbers (average trial size of 39
      participants); the methods of randomisation and concealment of allocation were
      poor or not stated in most trials. Blinded assessors were used in just over half
      of the trials and only 10 stated that they used intention-to-treat analysis.A
      wide variety of validated and customised outcome measures were used to assess the
      effectiveness of physiotherapy interventions. The most frequently reported
      physiotherapy outcomes were gait speed and timed up and go, in 19 and 15 trials
      respectively. Only five of the 43 trials reported data on falls (12%). The motor
      subscales of the Unified Parkinson's Disease Rating Scale and Parkinson's Disease
      Questionnaire-39 were the most commonly reported clinician-rated disability and
      patient-rated quality of life outcome measures, used in 22 and 13 trials
      respectively. The content and delivery of the physiotherapy interventions varied
      widely in the trials included within this review, so no quantitative meta
      analysis could be performed. AUTHORS' CONCLUSIONS: Considering the small number
      of participants examined, the methodological flaws in many of the studies, the
      possibility of publication bias, and the variety of interventions, formal
      comparison of the different physiotherapy techniques could not be performed.
      There is insufficient evidence to support or refute the effectiveness of one
      physiotherapy intervention over another in PD.This review shows that a wide range
      of physiotherapy interventions to treat PD have been tested . There is a need for
      more specific trials with improved treatment strategies to underpin the most
      appropriate choice of physiotherapy intervention and the outcomes measured.

PMID- 24936966
TI  - Music therapy for people with autism spectrum disorder.
AB  - BACKGROUND: The central impairments of people with autism spectrum disorder (ASD)
      affect social interaction and communication. Music therapy uses musical
      experiences and the relationships that develop through them to enable
      communication and expression, thus attempting to address some of the core
      problems of people with ASD. The present version of this review on music therapy
      for ASD is an update of the original Cochrane review published in 2006.
      OBJECTIVES: To assess the effects of music therapy for individuals with ASD.
      SEARCH METHODS: We searched the following databases in July 2013: CENTRAL, Ovid
      MEDLINE, EMBASE, LILACS, PsycINFO, CINAHL, ERIC, ASSIA, Sociological Abstracts,
      and Dissertation Abstracts International. We also checked the reference lists of
      relevant studies and contacted investigators in person. SELECTION CRITERIA: All
      randomised controlled trials (RCTs) or controlled clinical trials comparing music
      therapy or music therapy added to standard care to 'placebo' therapy, no
      treatment, or standard care for individuals with ASD were considered for
      inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently selected
      studies, assessed risk of bias, and extracted data from all included studies. We
      calculated the pooled standardised mean difference (SMD) and corresponding 95%
      confidence interval (CI) for continuous outcomes to allow the combination data
      from different scales and to facilitate the interpretation of effect sizes.
      Heterogeneity was assessed using the I2 statistic. In cases of statistical
      heterogeneity within outcome subgroups, we examined clients' age, intensity of
      therapy (number and frequency of therapy sessions), and treatment approach as
      possible sources of heterogeneity. MAIN RESULTS: We included 10 studies (165
      participants) that examined the short- and medium-term effect of music therapy
      interventions (one week to seven months) for children with ASD. Music was
      superior to 'placebo' therapy or standard care with respect to the primary
      outcomes social interaction within the therapy context (SMD 1.06, 95% CI 0.02 to
      2.10, 1 RCT, n = 10); generalised social interaction outside of the therapy
      context (SMD 0.71, 95% CI 0.18 to 1.25, 3 RCTs, n = 57, moderate quality
      evidence), non-verbal communicative skills within the therapy context (SMD 0.57,
      95% CI 0.29 to 0.85, 3 RCTs, n = 30), verbal communicative skills (SMD 0.33, 95%
      CI 0.16 to 0.49, 6 RCTs, n = 139), initiating behaviour (SMD 0.73, 95% CI 0.36 to
      1.11, 3 RCTs, n = 22, moderate quality evidence), and social-emotional
      reciprocity (SMD 2.28, 95% CI 0.73 to 3.83, 1 RCT, n = 10, low quality evidence).
      There was no statistically significant difference in non-verbal communicative
      skills outside of the therapy context (SMD 0.48, 95% CI -0.02 to 0.98, 3 RCTs, n
      = 57, low quality evidence). Music therapy was also superior to 'placebo' therapy
      or standard care in secondary outcome areas, including social adaptation (SMD
      0.41, 95% CI 0.21 to 0.60, 4 RCTs, n = 26), joy (SMD 0.96, 95% CI 0.04 to 1.88, 1
      RCT, n = 10), and quality of parent-child relationships (SMD 0.82, 95% CI 0.13 to
      1.52, 2 RCTs, n = 33, moderate quality evidence). None of the included studies
      reported any adverse effects. The small sample sizes of the studies limit the
      methodological strength of these findings. AUTHORS' CONCLUSIONS: The findings of
      this updated review provide evidence that music therapy may help children with
      ASD to improve their skills in primary outcome areas that constitute the core of
      the condition including social interaction, verbal communication, initiating
      behaviour, and social-emotional reciprocity. Music therapy may also help to
      enhance non-verbal communication skills within the therapy context. Furthermore,
      in secondary outcome areas, music therapy may contribute to increasing social
      adaptation skills in children with ASD and to promoting the quality of parent
      child relationships. In contrast to the studies included in an earlier version of
      this review published in 2006, the new studies included in this update enhanced
      the applicability of findings to clinical practice. More research using larger
      samples and generalised outcome measures is needed to corroborate these findings
      and to examine whether the effects of music therapy are enduring. When applying
      the results of this review to practice, it is important to note that the
      application of music therapy requires specialised academic and clinical training.

PMID- 24936969
TI  - Molecular mechanism of selective binding of peptides to silicon surface.
AB  - Despite extensive recent research efforts on material-specific peptides, the
      fundamental problem to be explored yet is the molecular interactions between
      peptides and inorganic surfaces. Here we used computer simulations (density
      functional theory and classical molecular dynamics) to investigate the adsorption
      mechanism of silicon-binding peptides and the role of individual amino acids in
      the affinity of peptides for an n-type silicon (n(+)-Si) semiconductor. Three
      silicon binding 12-mer peptides previously elaborated using phage display
      technology have been studied. The peptides' conformations close to the surface
      have been determined and the best-binding amino acids have been identified.
      Adsorption energy calculations explain the experimentally observed different
      degrees of affinity of the peptides for n(+)-Si. Our residual scanning analysis
      demonstrates that the binding affinity relies on both the identity of the amino
      acid and its location in the peptide sequence. 

PMID- 24936970
TI  - FINA-Yakult consensus statement on nutrition for the aquatic sports.

PMID- 24936972
TI  - Alkoxyamines: toward a new family of theranostic agents against cancer.
AB  - Theranostics combines therapeutic and diagnostic or drug deposition monitoring
      abilities of suitable molecules. Here we describe the first steps of building an
      alkoxyamine-based theranostic agent against cancer. The labile alkoxyamine ALK-1
      (t(1/2) = 50 min at 37  degrees C) cleaves spontaneously to generate (1) a highly
      reactive free alkyl radical used as therapeutic agents to induce cell damages
      leading to cell death and (2) a stable nitroxide used as contrast agent for
      Overhauser-enhanced magnetic resonance imaging (OMRI). The ALK-1 toxicity was
      studied extensively in vitro on the glioblastoma cell line U87-MG. Cell viability
      appeared to be dependent on ALK-1 concentration and on the time of the
      observation following alkoxyamine treatment. For instance, the LC50 at 72 h was
      250 MUM. Data showed that cell toxicity was specifically due to the in situ
      released alkyl radical. This radical induced oxidative stress, mitochondrial
      changes, and ultimately the U87 cell apoptosis. The nitroxide production, during
      the alkoxyamine homolysis, was monitored by OMRI, showing a progressive MRI
      signal enhancement to 6-fold concomitant to the ALK-1 homolysis. In conclusion,
      we have demonstrated for the first time that the alkoxyamines are promising
      molecules to build theranostic tools against solid tumors.

PMID- 24936971
TI  - Involvement of Rho-family GTPases in axon branching.
AB  - Development of the nervous system requires efficient extension and guidance of
      axons and dendrites culminating in synapse formation. Axonal growth and
      navigation during embryogenesis are controlled by extracellular cues. Many of the
      same extracellular signals also regulate axonal branching. The emergence of
      collateral branches from the axon augments the complexity of nervous system
      innervation and provides an additional mechanism for target selection. Rho-family
      GTPases play an important role in regulating intracellular cytoskeletal and
      signaling pathways that facilitate axonal morphological changes. RhoA/G and Rac1
      GTPase functions are complex and they can induce or inhibit branch formation,
      depending on neuronal type, cell context or signaling mechanisms. Evidence of a
      role of Cdc42 in axon branching is mostly lacking. In contrast, Rac3 has thus far
      been implicated in the regulation of axon branching. Future analysis of the
      upstream regulators and downstream effectors mediating the effects of Rho-family
      GTPase will provide insights into the cellular processes effected, and shed light
      on the sometimes opposing roles of these GTPases in the regulation of axon
      branching. 

PMID- 24936973
TI  - Present-day vegetation helps quantifying past land cover in selected regions of
      the Czech Republic.
AB  - The REVEALS model is a tool for recalculating pollen data into vegetation
      abundances on a regional scale. We explored the general effect of selected
      parameters by performing simulations and ascertained the best model setting for
      the Czech Republic using the shallowest samples from 120 fossil sites and data on
      actual regional vegetation (60 km radius). Vegetation proportions of 17 taxa were
      obtained by combining the CORINE Land Cover map with forest inventories,
      agricultural statistics and habitat mapping data. Our simulation shows that
      changing the site radius for all taxa substantially affects REVEALS estimates of
      taxa with heavy or light pollen grains. Decreasing the site radius has a similar
      effect as increasing the wind speed parameter. However, adjusting the site radius
      to 1 m for local taxa only (even taxa with light pollen) yields lower, more
      correct estimates despite their high pollen signal. Increasing the background
      radius does not affect the estimates significantly. Our comparison of estimates
      with actual vegetation in seven regions shows that the most accurate relative
      pollen productivity estimates (PPEs) come from Central Europe and Southern
      Sweden. The initial simulation and pollen data yielded unrealistic estimates for
      Abies under the default setting of the wind speed parameter (3 m/s). We therefore
      propose the setting of 4 m/s, which corresponds to the spring average in most
      regions of the Czech Republic studied. Ad hoc adjustment of PPEs with this
      setting improves the match 3-4-fold. We consider these values (apart from four
      exceptions) to be appropriate, because they are within the ranges of standard
      errors, so they are related to original PPEs. Setting a 1 m radius for local taxa
      (Alnus, Salix, Poaceae) significantly improves the match between estimates and
      actual vegetation. However, further adjustments to PPEs exceed the ranges of
      original values, so their relevance is uncertain. 

PMID- 24936974
TI  - Effects of spatial and feature attention on disparity-rendered structure-from
      motion stimuli in the human visual cortex.
AB  - An important advance in the study of visual attention has been the identification
      of a non-spatial component of attention that enhances the response to similar
      features or objects across the visual field. Here we test whether this non
      spatial component can co-select individual features that are perceptually bound
      into a coherent object. We combined human psychophysics and functional magnetic
      resonance imaging (fMRI) to demonstrate the ability to co-select individual
      features from perceptually coherent objects. Our study used binocular disparity
      and visual motion to define disparity structure-from-motion (dSFM) stimuli.
      Although the spatial attention system induced strong modulations of the fMRI
      response in visual regions, the non-spatial system's ability to co-select
      features of the dSFM stimulus was less pronounced and variable across subjects.
      Our results demonstrate that feature and global feature attention effects are
      variable across participants, suggesting that the feature attention system may be
      limited in its ability to automatically select features within the attended
      object. Careful comparison of the task design suggests that even minor
      differences in the perceptual task may be critical in revealing the presence of
      global feature attention. 

PMID- 24936975
TI  - Extracting the globally and locally adaptive backbone of complex networks.
AB  - A complex network is a useful tool for representing and analyzing complex
      systems, such as the world-wide web and transportation systems. However, the
      growing size of complex networks is becoming an obstacle to the understanding of
      the topological structure and their characteristics. In this study, a globally
      and locally adaptive network backbone (GLANB) extraction method is proposed. The
      GLANB method uses the involvement of links in shortest paths and a statistical
      hypothesis to evaluate the statistical importance of the links; then it extracts
      the backbone, based on the statistical importance, from the network by filtering
      the less important links and preserving the more important links; the result is
      an extracted subnetwork with fewer links and nodes. The GLANB determines the
      importance of the links by synthetically considering the topological structure,
      the weights of the links and the degrees of the nodes. The links that have a
      small weight but are important from the view of topological structure are not
      belittled. The GLANB method can be applied to all types of networks regardless of
      whether they are weighted or unweighted and regardless of whether they are
      directed or undirected. The experiments on four real networks show that the link
      importance distribution given by the GLANB method has a bimodal shape, which
      gives a robust classification of the links; moreover, the GLANB method tends to
      put the nodes that are identified as the core of the network by the k-shell
      algorithm into the backbone. This method can help us to understand the structure
      of the networks better, to determine what links are important for transferring
      information, and to express the network by a backbone easily. 

PMID- 24936977
TI  - Overexpression of SMPX in adult skeletal muscle does not change skeletal muscle
      fiber type or size.
AB  - Mechanical factors such as stretch are thought to be important in the regulation
      of muscle phenotype. Small muscle protein X-linked (SMPX) is upregulated by
      stretch in skeletal muscle and has been suggested to serve both as a
      transcription factor and a mechanosensor, possibly giving rise to changes in both
      fiber size and fiber type. We have used in vivo confocal imaging to study the
      subcellular localization of SMPX in skeletal muscle fibers of adult rats using a
      SMPX-EGFP fusion protein. The fusion protein was localized predominantly in
      repetitive double stripes flanking the Z-disc, and was excluded from all nuclei.
      This localization would be consistent with SMPX being a mechanoreceptor, but not
      with SMPX playing a role as a transcription factor. In vivo overexpression of
      ectopic SMPX in skeletal muscle of adult mice gave no significant changes in
      fiber type distribution or cross sectional area, thus a role of SMPX in
      regulating muscle phenotype remains unclear. 

PMID- 24936978
TI  - Identifying emerging motif in growing networks.
AB  - As function units, network motifs have been detected to reveal evolutionary
      mechanisms of complex systems, such as biological networks, food webs,
      engineering networks and social networks. However, emergence of motifs in growing
      networks may be problematic due to large fluctuation of subgraph frequency in the
      initial stage. This paper contributes to present a method which can identify the
      emergence of motif in growing networks. Based on the Erdos-Renyi(E-R) random null
      model, the variation rate of expected frequency of subgraph at adjacent time
      points was used to define the suitable detection range for motif identification.
      Upper and lower boundaries of the range were obtained in analytical form
      according to a chosen risk level. Then, the statistical metric Z-score was
      extended to a new one, Z(continuous), which effectively reveals the statistical
      significance of subgraph in a continuous period of time. In this paper, a novel
      research framework of motif identification was proposed, defining critical
      boundaries for the evolutionary process of networks and a significance metric of
      time scale. Finally, an industrial ecosystem at Kalundborg was adopted as a case
      study to illustrate the effectiveness and convenience of the proposed
      methodology.

PMID- 24936976
TI  - Standardized metadata for human pathogen/vector genomic sequences.
AB  - High throughput sequencing has accelerated the determination of genome sequences
      for thousands of human infectious disease pathogens and dozens of their vectors.
      The scale and scope of these data are enabling genotype-phenotype association
      studies to identify genetic determinants of pathogen virulence and
      drug/insecticide resistance, and phylogenetic studies to track the origin and
      spread of disease outbreaks. To maximize the utility of genomic sequences for
      these purposes, it is essential that metadata about the pathogen/vector isolate
      characteristics be collected and made available in organized, clear, and
      consistent formats. Here we report the development of the GSCID/BRC Project and
      Sample Application Standard, developed by representatives of the Genome
      Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource
      Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of
      Allergy and Infectious Diseases (NIAID), part of the National Institutes of
      Health (NIH), informed by interactions with numerous collaborating scientists. It
      includes mapping to terms from other data standards initiatives, including the
      Genomic Standards Consortium's minimal information (MIxS) and NCBI's
      BioSample/BioProjects checklists and the Ontology for Biomedical Investigations
      (OBI). The standard includes data fields about characteristics of the organism or
      environmental source of the specimen, spatial-temporal information about the
      specimen isolation event, phenotypic characteristics of the pathogen/vector
      isolated, and project leadership and support. By modeling metadata fields into an
      ontology-based semantic framework and reusing existing ontologies and minimum
      information checklists, the application standard can be extended to support
      additional project-specific data fields and integrated with other data
      represented with comparable standards. The use of this metadata standard by all
      ongoing and future GSCID sequencing projects will provide a consistent
      representation of these data in the BRC resources and other repositories that
      leverage these data, allowing investigators to identify relevant genomic
      sequences and perform comparative genomics analyses that are both statistically
      meaningful and biologically relevant. 

PMID- 24936979
TI  - Retinal imaging as a source of biomarkers for diagnosis, characterization and
      prognosis of chronic illness or long-term conditions.
AB  - The black void behind the pupil was optically impenetrable before the invention
      of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal
      imaging and image processing, especially over the past decade, have opened a
      route to another unexplored landscape, the retinal neurovascular architecture and
      the retinal ganglion pathways linking to the central nervous system beyond.
      Exploiting these research opportunities requires multidisciplinary teams to
      explore the interface sitting at the border between ophthalmology, neurology and
      computing science. It is from the detail and depth of retinal phenotyping that
      novel metrics and candidate biomarkers are likely to emerge. Confirmation that in
      vivo retinal neurovascular measures are predictive of microvascular change in the
      brain and other organs is likely to be a major area of research activity over the
      next decade. Unlocking this hidden potential within the retina requires
      integration of structural and functional data sets, that is, multimodal mapping
      and longitudinal studies spanning the natural history of the disease process. And
      with further advances in imaging, it is likely that this area of retinal research
      will remain active and clinically relevant for many years to come. Accordingly,
      this review looks at state-of-the-art retinal imaging and its application to
      diagnosis, characterization and prognosis of chronic illness or long-term
      conditions. 

PMID- 24936981
TI  - The emergence densities of annual cicadas (Hemiptera: Cicadidae) increase with
      sapling density and are greater near edges in a bottomland hardwood forest.
AB  - The emergence densities of cicadas tend to be patchy at multiple spatial scales.
      While studies have identified habitat conditions related to these patchy
      distributions, their interpretation has been based primarily on periodical cicada
      species; habitat factors associated with densities of nonperiodical (i.e.,
      annual) cicadas have remained under studied. This is despite their widespread
      distribution, diversity, and role as an important trophic resource for many other
      organisms, particularly within riparian areas. We studied habitat factors
      associated with the emergence densities of Tibicen spp. in a bottomland hardwood
      forest in east-central Arkansas. We found emergence densities were greatest in
      areas of high sapling densities and increased toward forest edges, although
      sapling density was a much stronger predictor of emergence density. Emergence
      densities also differed among sample areas within our study system. The habitat
      features predicting nymph densities were likely driven by a combination of
      factors affecting female selection of oviposition sites and the effects of
      habitat conditions on nymph survival. The differences in nymph densities between
      areas of our system were likely a result of the differential effects of flooding
      in these areas. Interestingly, our findings were similar to observations of
      periodical species, suggesting that both types of cicadas select similar habitat
      characteristics for ovipositing or are under comparable selective pressures
      during development. Our findings also imply that changes in habitat
      characteristics because of anthropogenically altered disturbance regimes (e.g.,
      flooding) have the potential to negatively impact both periodical and annual
      species, which could have dramatic consequences for organisms at numerous trophic
      levels. 

PMID- 24936980
TI  - Imaging of acute stroke prior to treatment: current practice and evolving
      techniques.
AB  - Standard imaging in acute stroke is undertaken with the aim of diagnosing the
      underlying cause and excluding stroke mimics. In the presence of ischaemic
      stroke, imaging is also needed to assess patient suitability for treatment with
      intravenous thrombolysis. Non-contrast CT is predominantly used, but MRI can also
      exclude any contraindications to thrombolysis treatment. Advanced stroke imaging
      such as CT and MR angiography and perfusion imaging are increasingly used in an
      acute setting. In this review, we discuss the evidence for the application of
      these advanced techniques in the imaging of acute stroke. 

PMID- 24936982
TI  - Stable isotopes reveal rail-associated behavior in a threatened carnivore.
AB  - Human-wildlife conflict is a leading cause of adult mortality for large
      carnivores worldwide. Train collision is the primary cause of mortality for
      threatened grizzly bears (Ursus arctos) in Banff National Park. We investigated
      the use of stable isotope analysis as a tool for identifying bears that use the
      railway in Banff. Rail-associated bears had higher delta(15)N and delta(34)S
      values than bears sampled away from the rail, but similar delta(13)C values.
      Because elevated delta(15)N values are indicative of higher animal protein
      consumption, rail-associated bears likely preyed on ungulates that foraged along
      the rail or scavenged on train-killed animals. The higher delta(34)S values in
      bear hair could have resulted from bears consuming sulfur pellets spilled on the
      rail or through the uptake of sulfur in the plants bears or animals consumed.
      Similar delta(13)C values suggest that the two types of bears had generally
      similar plant-based diets. Results from this study suggest that stable isotopes
      analysis could be used as a non-invasive, affordable, and efficient technique to
      identify and monitor bears that forage on the railway in Banff and potentially
      other transportation corridors worldwide. 

PMID- 24936985
TI  - Editorial.

PMID- 24936984
TI  - Pediatric oncology as the next global child health priority: the need for
      national childhood cancer strategies in low- and middle-income countries.

PMID- 24936983
TI  - Antibody quantum dot conjugates developed via copper-free click chemistry for
      rapid analysis of biological samples using a microfluidic microsphere array
      system.
AB  - Antibody-based proteomics is an enabling technology that has significant
      implications for cancer biomarker discovery, diagnostic screening, prognostic and
      pharmacodynamic evaluation of disease state, and targeted therapeutics. Quantum
      dot based fluoro-immunoconjugates possess promising features toward realization
      of this goal such as high photostability, brightness, and multispectral
      tunability. However, current strategies to generate such conjugates are riddled
      with complications such as improper orientation of antigen binding sites of the
      antibody, aggregation, and stability issues. We report a facile yet effective
      strategy to conjugate anti-epidermal growth factor receptor (EGFR) antibody to
      quantum dots using copper-free click reaction, and compared them to similar
      constructs prepared using traditional strategies such as succinimidyl-4-(N
      maleimidomethyl) cyclohexane-1-carboxylate (SMCC) and biotin-streptavidin
      schemes. The Fc and Fab regions of the conjugates retain their binding potential,
      compared to those generated through the traditional schemes. We further applied
      the conjugates in testing a novel microsphere array device designed to carry out
      sensitive detection of cancer biomarkers through fluoroimmunoassays. Using
      purified EGFR, we determined the limit of detection of the microscopy centric
      system to be 12.5 ng/mL. The biological assay, in silico, was successfully tested
      and validated by using tumor cell lysates, as well as human serum from breast
      cancer patients, and the results were compared to normal serum. A pattern
      consistent with established clinical data was observed, which further validates
      the effectiveness of the developed conjugates and its successful implementation
      both in vitro as well as in silico fluoroimmunoassays. The results suggest the
      potential development of a high throughput in silico paradigm for predicting the
      class of patient cancer based on EGFR expression levels relative to normal
      reference levels in blood. 

PMID- 24936986
TI  - Guest Editor's Introduction.

PMID- 24936987
TI  - Depression comorbid with anxiety or medical illness: The role of paroxetine.
AB  - Depression is a common illness, frequently comorbid with other psychiatric
      disorders or medical illness. Comorbidity is associated with a poorer outcome for
      the patient, more severe symptoms and risk of suicide. The selective serotonin re
      uptake inhibitor paroxetine has proven efficacy in the treatment of depression
      and anxiety disorders, including panic disorder, obsessive compulsive disorder
      and social anxiety disorder. The paper examines the role of paroxetine
      monotherapy in the treatment of depressed patients with comorbid anxiety, and
      reviews the use of paroxetine in the treatment of depression in patients
      suffering concurrent medical illnesses. ( Int J Psych Clin Pract 2001; 5:3-10). 

PMID- 24936988
TI  - Improved ability to identify symptoms of major depressive disorder (MDD) in
      general practice.
AB  - The diagnosis and treatment of major depressive disorder (MDD) is a primary care
      responsibility in most countries, yet although most people with MDD present to
      their primary care team at some time during the course of their illness, the
      majority remain unrecognized and fewer still are effectively treated. Large-scale
      epidemiological studies have helped to identify several factors that influence
      recognition rates of MDD in primary care. Patients who present with psychological
      symptoms and clearly communicate their disability are more likely to be
      recognized than those who present with somatic symptoms or concurrent physical
      illnesses. Fatigue, loss of energy and poor motivation are core symptoms of
      depression in most patients, but are rarely interpreted as psychological symptoms
      and frequently mislead the primary care physician into searching for a somatic
      cause. If primary care recognition rates for MDD are to improve substantially,
      patients must be encouraged to seek help if they are suffering from these three
      core symptoms, and primary care physicians must increase their index of suspicion
      for MDD if a patient presents with them. Simple screening tools such as the Mini
      International Neuropsychiatric Interview (MINI) can help to improve recognition
      rates significantly and should be applied routinely in primary care. ( Int J
      Psych Clin Pract 2001; 5 (Suppl 1): S3 - S10). 

PMID- 24936989
TI  - Managing major depression: improving the interface between psychiatrists and
      primary care.
AB  - Responsibility for identifying and managing most people with major depressive
      disorder (MDD) rests firmly within the primary care setting. Unfortunately,
      circumstances continue to have a negative impact on depression outcomes, with low
      recognition rates, inadequate levels of treatment and poor follow-up all
      contributing to the provision of a less than optimal service for patients. The
      Hampshire Depression Project confirmed that improved primary care education, in
      isolation, does not have any long-term benefits for patients with MDD. However,
      many other studies have shown that stronger collaboration between psychiatrists
      and primary care can significantly improve the quality of care provided in the
      primary care setting, and ensure that most patients are managed effectively and
      in accordance with international and national guidelines. Simple collaborative
      care models, which encourage mental health specialists to work within the primary
      care system, have had a dramatic impact on the outcomes for patients, and
      significantly enhanced the satisfaction of both patients and physicians with
      treatment. These interventions could easily and cost-effectively be applied more
      broadly and would ensure that effective management of MDD in primary care becomes
      the rule and not just the exception. ( Int J Psych Clin Pract 2001; 5 (Suppl 1):
      S11-S18). 

PMID- 24936990
TI  - Post-traumatic stress disorder: A review for the general psychiatrist.
AB  - Post-traumatic stress disorder affects about one in every hundred of the
      population at any particular time. Aetiological factors include genetics,
      personality, a background of psychiatric problems, the personal meaning of the
      traumatic event, issues of proximity or intensity, childhood abuse, and the
      initial emotional response to stress. Many precipitants are known, ranging from
      combat through rape or torture to difficult parturition. Core symptoms are
      reflective of the traumatic precipitant. Prolonged symptoms are associated with
      prior psychiatric or physical problems, poverty, repeated assault, alcohol or
      drug abuse, and cultural factors. Co-morbidity is high, especially for
      depression, alcohol and drug misuse. Reduced hippocampal volume, corticosteroid
      abnormalities, and adrenergic overactivity have been described. The use of
      official criteria and specific measuring instruments help in differential
      diagnosis. Management needs to be tailored to the needs of the individual and the
      stage of the disorder, and includes psychotherapy, antidepressants, and the newer
      eye-movement desensitization and reprocessing approach. ( Int J Psych Clin Pract
      2001; 5:11-18). 

PMID- 24936991
TI  - Antidepressants: pharmacological profile and clinical consequences.
AB  - Three neurotransmitter systems are implicated in the biological basis of
      depression: the serotonergic system is thought to be a major component in the
      development of depression and in the efficacy of antidepressant drugs, while the
      noradrenergic and dopaminergic systems play lesser roles, but are important in
      the development of antidepressant side-effects. Selective serotonin re-uptake
      inhibitors (SSRIs) are still the drug treatments of choice in major depressive
      disorder, but each has a subtly different pharmacological profile, which has
      implications for pharmacodynamic actions and clinical efficacy and side-effect
      profiles. Although the precise mechanisms responsible for specific depressive
      symptoms are not yet well defined, evidence is emerging that some SSRIs may be
      more effective in combating certain symptoms than others. Fluoxetine appears to
      be particularly effective in overcoming symptoms of fatigue and low energy,
      whereas paroxetine or sertraline may be more appropriately used for depressed
      patients experiencing anxiety. A growing understanding of molecular mechanisms in
      depression and the unique clinical consequences of each pharmacological agent
      brings us one step closer to being able to individualize antidepressant treatment
      on the basis of core presenting symptoms and the needs of the individual patient.
      ( Int J Psych Clin Pract 2001; 5 (Suppl 1): S19-S28). 

PMID- 24936992
TI  - Quality of life in schizophrenia: Impact of psychopathology, patients' gender and
      antipsychotic treatment.
AB  - Quality of life (QoL) was evaluated in 100 schizophrenic patients treated with
      classic or atypical neuroleptics in a day hospital. The severity of schizophrenia
      was evaluated with the PANSS scale and QoL with the SF36 questionnaire. Both the
      patients' global QoL and several QoL domains improved after treatment. The QoL of
      female and male patients did not differ at baseline, but the improvement after
      treatment was greater in female patients, and in female patients the QoL
      improvement correlated positively with the improvement in PANSS general symptoms.
      The severity of depressive symptoms of schizophrenic patients correlated
      inversely with the total QoL, at both the start and end of the study. The
      improvement of general schizophrenic and depressive symptoms correlated
      positively with the improvement in QoL. The improvement in QoL in patients
      treated with classic neuroleptics differed only insignificantly after treatment,
      in comparison to that in patients receiving 'old' atypical drugs. However, the
      negative correlation between QoL improvement and improvement in PANSS total
      score, as well as in PANSS depressive symptoms, was found only among patients
      treated with classic neuroleptics. Neuroleptic-induced extrapyramidal symptoms
      were more severe in patients receiving classic neuroleptics but these did not
      have an impact on patients' QoL. ( Int J Psych Clin Pract 2001; 5:19-26). 

PMID- 24936993
TI  - Cardiovascular reflexes during treatment of social phobia with moclobemide.
AB  - INTRODUCTION: Cardiovascular side-effects are less frequent with moclobemide than
      with tricyclic or monoamine oxidase inhibitor antidepressants. We performed a
      detailed assessment of cardiovascular reflexes in 15 patients meeting DSM-III-R
      criteria for social phobia, before treatment and whilst taking a stable dose of
      moclobemide for a median of 7 weeks. METHOD: Cardiovascular reflex responses to
      standing, deep breathing and the Valsalva manoeuvre were assessed using beat-by
      beat blood pressure and heart rate recording. RESULTS: Moclobemide produced a
      statistically significant, but clinically modest, degree of improvement in social
      phobia symptoms. Only the maximum change in heart rate from supine to standing
      showed a change from before to after treatment, which was not statistically
      significant after Bonferroni correction, and there was no consistent pattern of
      altered sympathetic or parasympathetic function. CONCLUSION: Moclobemide is
      relatively devoid of cardiovascular autonomic effects in physically healthy
      subjects with social phobia. ( Int J Psych Clin Pract 2001; 5:27-31).

PMID- 24936994
TI  - Compliance and acceptance in antidepressant treatment.
AB  - Poor compliance with antidepressant medication is widespread in both primary care
      and psychiatric practice, and is a major obstacle to the effective management of
      depression. It is often believed that adverse events and a lack of efficacy
      associated with inappropriate prescribing of older antidepressants are common
      reasons why patients discontinue treatment prematurely. However, appropriate
      prescribing of effective and well-tolerated antidepressants does not necessarily
      guarantee compliance. A patient's core beliefs and attitudes to treatment also
      influence the chances of successful management, and studies have shown that
      patients harbour many unfounded beliefs relating to antidepressant medications
      and their use. The prescribing physician is therefore duty bound not only to
      ensure that they chose an effective antidepressant with minimal side-effects and
      prescribe it according to treatment guidelines, but that they actively explore
      the patient's beliefs and attitudes at the time of treatment. Addressing common
      misconceptions about antidepressant medications, and undertaking a structured
      follow-up, have been shown both to enhance compliance and improve treatment
      outcomes. The choice of newer, more selective antidepressants results in a higher
      number of patients achieving at least one month of treatment. The choice of a
      drug with a once-daily treatment regimen (drugs with a longer half-life) and with
      a low risk for discontinuation symptoms if doses are occasionally missed is also
      warranted. ( Int J Psych Clin Pract 2001; 5 (Suppl 1): S29-S35). 

PMID- 24936995
TI  - In vivo cardiovascular effects of the new atypical neuroleptic sertindole.
AB  - INTRODUCTION: The goal of this open clinical study was to perform a detailed
      investigation of the cardiovascular effects of the novel atypical neuroleptic
      sertindole. METHOD: Thirty initially untreated schizophrenic inpatients
      (diagnosed according to DSM-III-R) underwent a total of 103 serial recordings of
      standardized autonomic tests during a sertindole dose titration programme (4-16
      mg/d). The autonomic test battery included: (1) conventional ECGs with 12
      channels, (2) computer-assisted analysis of the 5-min resting heart rate
      variability (HRV); (3) HRV during standard autonomic reflex tests (deep breathing
      test, 30:15 ratio); and (4) blood pressure measurement under resting conditions
      and during orthostatic stress (Schellong test). Reference values for the HRV
      study were obtained from healthy controls ( n =80). RESULTS: The most important
      findings were: (1) sertindole significantly increased the resting heart rate; (2)
      sertindole induced a significant and probably dose-dependent prolongation of the
      frequency-corrected QT-times, while mean PQ-conduction times remained unchanged;
      (3) sertindole had no significant effects on autonomic parasympathetic tone, both
      in the resting study and following the autonomic reflex tests; and (4) sertindole
      at doses between 4 and 16 mg/d did not significantly influence blood pressure
      either under resting conditions or during orthostatic stress. CONCLUSION: The
      implications of these findings for the cardiovascular safety and tolerance of
      sertindole are discussed comprehensively, while considering the
      pathophysiologically relevant mechanisms underlying the appearance of life
      threatening cardiac arrhythmias and sudden cardiac death. ( Int J Psych Clin
      Pract 2001; 5:33-40).

PMID- 24936996
TI  - Major depressive disorder (MDD) from the patient's perspective: overcoming
      barriers to appropriate care.
AB  - Major depressive disorder is a highly stigmatized condition which, despite its
      prevalence in primary care, is broadly unrecognized and consistently poorly
      treated. Epidemiological studies reveal a disconcerting lack of understanding
      about depression within the general population, and this invariably affects
      patients' attitudes to treatment. Public opinion polls have found a widespread
      distrust of antidepressant medications, and most members of the public would
      prefer a psychosocial or alternative approach to treatment to a pharmacological
      one. Public awareness initiatives such as the UK's Defeat Depression Campaign
      have helped to positively shift public attitudes towards depression and its
      treatment, but misconceptions about antidepressant medications appear especially
      entrenched. The landmark DEPRES study found that over 40% of patients did not
      consult their doctors for their depression, and only 30% of consulters received
      an antidepressant. Six clearly differentiated patient clusters were also
      identified in this study, suggesting that treatment might be selected on the
      basis of individual symptom profiles and other key differentiating factors. By
      understanding our patients' perspectives on depression and its management, it
      should be possible to improve rates of consultation and overcome resistance to
      antidepressant treatment. Only by achieving both of these goals in parallel will
      we really be making progress towards optimal management of major depression. (
      Int J Psych Clin Pract 2001; 5 (Suppl 1): S37-S42). 

PMID- 24936997
TI  - Preliminary validation of a UK-modified version of the BASIS-32.
AB  - INTRODUCTION: The authors examined the reliability and validity of a UK-modified
      version of the Behavioral and Symptom Identification Scale (BASIS-32). METHOD:
      Data from two samples of patients from acute psychiatric inpatient settings were
      used in the analyses ( n =303, n =92). The factor structure of the scale differed
      from that of the original BASIS-32. RESULTS: Five factors emerged: (i) depression
      and anxiety, (ii) lability, (iii) psychosis, (iv) substance misuse and (v)
      functioning. The full scale of the modified BASIS demonstrated high internal
      consistency (Cronbach's alpha=0.93). Internal consistency for the subscales
      ranged from 0.86 to 0.45. The depression and anxiety subscale discriminated
      patients with a diagnosis of unipolar depression from those with other diagnoses
      (median score=3.11 (Inter quartile range (IQR)=2.67,3.33) versus median
      score=2.44 (1.67,3.11), P < 0.001). The substance misuse subscale discriminated
      patients with a diagnosis of alcohol or opiate dependence from those with other
      diagnoses (median score=2.33 (2, 3) versus median score=1.33 (0.67, 2), P <
      0.001). However, the psychosis subscale did not differentiate patients with a
      psychotic illness from those with a nonpsychotic diagnosis (median score=1.4
      (0.6,2.4) versus median score=1.2, (0.6,2), P = 0.16). CONCLUSION: The total
      scale appeared to be at least as good as the Brief Symptom Inventory (BSI) in its
      responsiveness to change. The effect size for the BASIS=1.17 versus 0.91 for the
      BSI. Convergent validity was partially demonstrated between the modified BASIS
      and the BSI. ( Int J Psych Clin Pract 2001; 5:41-48).

PMID- 24936998
TI  - Prevalence of clinical (major) depression in general practice using the DSM-IV
      version of PRIME-MD.
AB  - INTRODUCTION: PRIME-MD (Primary Care Evaluation of Mental Disorder) has been
      developed to detect the most frequent mental disorders in general practice.
      METHOD: A prevalence study with the Danish PRIME-MD's module for major depression
      was carried out by general practitioners. In total, 16 practices and 2501
      patients were involved in the study. RESULTS: The patient questionnaire part of
      the PRIME-MD was completed by more than 95% of the patients, indicating a high
      applicability. Around 8% of all patients included suffered from major depression.
      Of these, the ratio of females to males was 2:1. Three factors were identified in
      the questionnaire: depression, psychosomatic distress, and alcohol use. Compared
      to the non-depressed patients, the patients with major depression evaluated their
      health condition as being considerably impaired. CONCLUSION: PRIME-MD is highly
      applicable in general practice. ( Int J Psych Clin Pract 2001; 5:49-54).

PMID- 24936999
TI  - Investigation of 'borderline' dementia, particularly of Alzheimer's type,
      compared with non-demented patients with similar neuropsychological profiles.
AB  - INTRODUCTION: The aim of the study was to test the fine ability of the Cambridge
      Cognitive Examination (CAMCOG) to differentiate between subjects with mild
      dementia and non-demented subjects. MATERIAL AND METHODS: Ninety-four subjects
      took part in the study (56 non-demented and 38 mildly demented). Diagnosis was
      reached according to DSM-IV and NINCDS-ADRDA criteria. RESULTS: Items 160, 146,
      171 and 178 seemed to be particularly useful for the diagnosis for subjects under
      75 years of age, and items 139, 143, 146, 148, 159, 175, 177, 181, 183 and 186
      for the diagnosis for subjects over 74. DISCUSSION: Further study of these items
      may increase ability to detect dementia in epidemiological surveys and advance
      knowledge about the role of factors like education or culture in interaction with
      advanced age. Currently, it is not possible to identify dementia at an early
      stage by neuropsychological methods alone. ( Int J Psych Clin Pract 2001; 5:55
      61).

PMID- 24937000
TI  - Clinical experience with olanzapine in the course of post-operative delirium
      associated with psychosis in geriatric patients: A report of three cases.
AB  - Olanzapine treatment was initiated with three geriatric patients who manifested
      symptoms of psychosis associated with post-operative delirium. The patients'
      response was assessed by the clinical observation of their behavior. Since post
      operative delirium is time-limited, and can spontaneously remit, no conclusions
      regarding the efficacy of olanzapine in reversing delirium can be made. However
      it is speculated that olanzapine may have shortened the duration of the
      associated psychosis. These case reports offered the opportunity to illustrate
      the pharmacological actions, the convenient dosing schedule and the side-effects
      profile of this atypical antipsychotic. ( Int J Psych Clin Pract 2001; 5:63-66). 

PMID- 24937001
TI  - Late-onset schizophrenia with epileptiform discharge.
AB  - We report the case of a 51-year-old woman with no history of psychosis or
      epilepsy, presenting with abrupt late-onset psychosis with prominent epileptiform
      discharges with a diffuse sharp and slow wave complex. She had auditory and
      somatic hallucinations, delusions and loosening of associations, but epileptic
      seizures such as disturbance of consciousness and convulsion were not observed.
      Other laboratory studies, including CT, magnetic resonance imaging, single photon
      emission computed tomography, and cerebrospinal fluid were normal. The
      epileptiform discharge disappeared within 10 days after starting treatment with
      sodium valproate. Clinical improvement commenced after the EEG improvement, and
      was complete. The cause remains obscure, but it was suggested that there were
      some organic factors in the etiology of this late-onset psychosis. ( Int J Psych
      Clin Pract 2001; 5:67-70). 

PMID- 24937002
TI  - Clozapine-induced concordant agranulocytosis in monozygotic twins.
AB  - Two monozygotic twin sisters were admitted to a psychiatric hospital and
      diagnosed as having first-episode schizophrenia. Clozapine treatment led to the
      complete remission of psychotic symptoms within a short time. In both twins the
      low leukocyte count was detected after 9 weeks of clozapine. Serological typing
      of the HLA system was performed and an identical pattern was detected in both
      twins: HLA-A: 28, 26; HLA-B: 49, 63; DR: 2 (vs 16), 12, 52; DQ:1. It is the first
      report of concordant manifestation of clozapine-induced agranulocytosis in
      monozygotic twins. Our case report of twins afflicted synchronously with
      schizophrenia and later with agranulocytosis after clozapine is of interest
      because it suggests that genetic factors may participate not only in timing of
      onset of schizophrenia, but also in the emergence and timing of agranulocytosis
      in response to clozapine treatment. ( Int J Psych Clin Pract 2001; 5:71-73). 

PMID- 24937003
TI  - Coexisting Diogenes and Capgras syndromes.
AB  - The co-occurrence of Diogenes and Capgras syndromes, both unusual in themselves,
      would be expected to be rare. A MEDLINE search using the terms Diogenes, Capgras,
      self-neglect and domestic squalor revealed no previous reports of this
      combination of disorders. Both conditions are somewhat dubiously named as &#164
      syndromes' when in fact they are probably no more than symptoms with different
      causes. Of particular interest in this case is the exacerbation of the self
      neglect, characteristic of the Diogenes syndrome, by the delusional
      misidentification which marks the Capgras syndrome; as well as the reinforcement
      of the previously recognised association with frontal lobe pathology. The role of
      medication, though limited, is described. ( Int J Psych Clin Pract 2001; 5:75
      76). 

PMID- 24937004
TI  - Topics in contemporary psychiatric practice: Neuroimaging.

PMID- 24937006
TI  - A method for detecting long non-coding RNAs with tiled RNA expression
      microarrays.
AB  - Long non-coding ribonucleic acids (lncRNAs) have been proposed as biomarkers in
      prostate cancer. This paper proposes a selection method which uses data from
      tiled microarrays to identify relatively long regions of moderate expression
      independent of the microarray platform and probe design. The method is used to
      search for candidate long non-coding ribonucleic acids (lncRNAs) at locus 8q24
      and is run on three independent experiments which all use samples from prostate
      cancer patients. The robustness of the method is tested by utilizing repeated
      copies of tiled probes. The method shows high consistency between experiments
      that used the same samples, but different probe layout. There also is
      statistically significant consistency when comparing experiments with different
      samples. The method selected the long non-coding ribonucleic acid PCNCR1 in all
      three experiments. 

PMID- 24937007
TI  - Peginterferon alfa-2a is associated with elevations in alanine aminotransferase
      at the end of treatment in chronic hepatitis C patients with sustained virologic
      response.
AB  - BACKGROUND: The purpose of this study was to investigate the incidence and
      demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at
      the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained
      virologic response (SVR). METHODS AND FINDINGS: Seven hundred naive CHC patients
      who underwent combination treatment between January 2003 and December 2010 were
      included in the study. The patients with SVR and serum ALT>upper limit of normal
      (ULN) at the EOT were further analyzed. The effects of clinical characteristics,
      treatment regimen, and virologic variables were evaluated by logistic regression.
      Of the 700 included patients, 488 (69.7%) achieved an SVR after treatment, and
      235 (33.6%) had serum ALT levels>ULN at the EOT. Of those 488 patients, 137
      (28.1%) had abnormal ALT values at the EOT. A multivariate analysis showed that
      the occurrence of ALT abnormalities at the EOT was significantly associated with
      pegylated interferon (PEG-IFN) alfa-2a (odds ratio [OR], 2.24; 95% confidence
      interval [CI], 1.45-3.45; P<0.001), baseline fatty liver (OR, 1.76; 95% CI, 1.16
      2.76; P = 0.007), and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35-4.09; P =
      0.002). CONCLUSIONS: Use of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are
      important factors associated with EOT-ALT abnormality in CHC patients receiving
      combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT
      elevation will become normal at the end of follow-up, but fatty liver and
      cirrhosis-related ALT elevation will not be resolved.

PMID- 24937009
TI  - Rhodium(III)-catalyzed cross-coupling of alkenylboronic acids and N
      pivaloyloxylamides.
AB  - Rh(III)-catalyzed umpolung amidation of alkenylboronic acids for the synthesis of
      enamides is reported. This reaction proceeds readily at room temperature and
      displays an extremely wide spectrum of functional group tolerance. With
      cooperation of hydroboration, it enables the formal anti-Markovnikov
      hydroamidation of terminal alkynes, stereospecifically affording the trans
      enamides in excellent yields. 

PMID- 24937010
TI  - A hard goodbye.

PMID- 24937008
TI  - Functional reorganization of the locomotor network in Parkinson patients with
      freezing of gait.
AB  - Freezing of gait (FoG) is a transient inability to initiate or maintain stepping
      that often accompanies advanced Parkinson's disease (PD) and significantly
      impairs mobility. The current study uses a multimodal neuroimaging approach to
      assess differences in the functional and structural locomotor neural network in
      PD patients with and without FoG and relates these findings to measures of FoG
      severity. Twenty-six PD patients and fifteen age-matched controls underwent
      resting-state functional magnetic resonance imaging and diffusion tensor imaging
      along with self-reported and clinical assessments of FoG. After stringent
      movement correction, fifteen PD patients and fourteen control participants were
      available for analysis. We assessed functional connectivity strength between the
      supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic
      nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR,
      respectively) within each hemisphere. Additionally, we quantified structural
      connectivity strength between locomotor hubs and assessed relationships with
      metrics of FoG. FoG+ patients showed greater functional connectivity between the
      SMA and bilateral MLR and between the SMA and left CLR compared to both FoG- and
      controls. Importantly, greater functional connectivity between the SMA and MLR
      was positively correlated with i) clinical, ii) self-reported and iii) objective
      ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural
      compensation. The current findings demonstrate a re-organization of functional
      communication within the locomotor network in FoG+ patients whereby the higher
      order motor cortex (SMA) responsible for gait initiation communicates with the
      MLR and CLR to a greater extent than in FoG- patients and controls. The observed
      pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS
      to compensate for the loss of connectivity between the STN and SMA and may
      reflect a loss of lower-order, automatic control of gait by the basal ganglia. 

PMID- 24937011
TI  - Polydispersity analysis of Taylor dispersion data: the cumulant method.
AB  - Taylor dispersion analysis is an increasingly popular characterization method
      that measures the diffusion coefficient, and hence the hydrodynamic radius, of
      (bio)polymers, nanoparticles, or even small molecules. In this work, we describe
      an extension to current data analysis schemes that allows size polydispersity to
      be quantified for an arbitrary sample, thereby significantly enhancing the
      potentiality of Taylor dispersion analysis. The method is based on a cumulant
      development similar to that used for the analysis of dynamic light scattering
      data. Specific challenges posed by the cumulant analysis of Taylor dispersion
      data are discussed, and practical ways to address them are proposed. We
      successfully test this new method by analyzing both simulated and experimental
      data for solutions of moderately polydisperse polymers and polymer mixtures. 

PMID- 24937012
TI  - Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.
AB  - Cisplatin is a chemotherapeutic agent, which is used in the treatment of various
      solid organ cancers, and its main dose limiting side effect of cisplatin is
      nephrotoxicity. The aim of this study is to investigate the role of pioglitazone
      and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system
      (RTCA) was used for real-time and time-dependent analysis of the cellular
      response of HK-2 cells following incubation with cisplatin and combination with
      creatine or pioglitazone hydrochloride. First, half-maximal inhibitory
      concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by
      RTCA system. Afterwards creatine and pioglitazone was administered with serial
      dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M * 10(-5) at 24th
      hour and 3.93 M * 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M *
      10(-3) at 24th hour and 2.85 M * 10(-4) at 48th hour. Although cells were treated
      the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither
      pioglitazone nor creatine had additional protective effect in any dose.
      Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced
      cell death could not be found. Further studies and clinical trials are needed to
      evaluate the effect of different doses of these drugs in cisplatin-induced
      nephrotoxicity.

PMID- 24937013
TI  - Dynamic functional brain networks involved in simple visual discrimination
      learning.
AB  - Visual discrimination tasks have been widely used to evaluate many types of
      learning and memory processes. However, little is known about the brain regions
      involved at different stages of visual discrimination learning. We used
      cytochrome c oxidase histochemistry to evaluate changes in regional brain
      oxidative metabolism during visual discrimination learning in a water-T maze at
      different time points during training. As compared with control groups, the
      results of the present study reveal the gradual activation of cortical
      (prefrontal and temporal cortices) and subcortical brain regions (including the
      striatum and the hippocampus) associated to the mastery of a simple visual
      discrimination task. On the other hand, the brain regions involved and their
      functional interactions changed progressively over days of training. Regions
      associated with novelty, emotion, visuo-spatial orientation and motor aspects of
      the behavioral task seem to be relevant during the earlier phase of training,
      whereas a brain network comprising the prefrontal cortex was found along the
      whole learning process. This study highlights the relevance of functional
      interactions among brain regions to investigate learning and memory processes. 

PMID- 24937014
TI  - Selective role for DNMT3a in learning and memory.
AB  - Methylation of cytosine nucleotides is governed by DNA methyltransferases (DNMTs)
      that establish de novo DNA methylation patterns in early embryonic development
      (e.g., DNMT3a and DNMT3b) or maintain those patterns on hemimethylated DNA in
      dividing cells (e.g., DNMT1). DNMTs continue to be expressed at high levels in
      mature neurons, however their impact on neuronal function and behavior are
      unclear. To address this issue we examined DNMT1 and DNMT3a expression following
      associative learning. We also generated forebrain specific conditional Dnmt1 or
      Dnmt3a knockout mice and characterized them in learning and memory paradigms as
      well as for alterations in long-term potentiation (LTP) and synaptic plasticity.
      Here, we report that experience in an associative learning task impacts
      expression of Dnmt3a, but not Dnmt1, in brain areas that mediate learning of this
      task. We also found that Dnmt3a knockout mice, and not Dnmt1 knockouts have
      synaptic alterations as well as learning deficits on several associative and
      episodic memory tasks. These findings indicate that the de novo DNA methylating
      enzyme DNMT3a in postmitotic neurons is necessary for normal memory formation and
      its function cannot be substituted by the maintenance DNA methylating enzyme
      DNMT1.

PMID- 24937016
TI  - Tailored weight loss intervention in obese adults within primary care practice:
      rationale, design, and methods of Choose to Lose.
AB  - Although there are efficacious weight loss interventions that can improve health
      and delay onset of diabetes and hypertension, these interventions have not been
      translated into clinical practice. The primary objective of this study is to
      evaluate the effectiveness and cost effectiveness of a tailored lifestyle
      intervention in primary care patients. Patients were recruited by their primary
      care physicians and eligible participants were randomized to an enhanced
      intervention or standard intervention. All participants met with a lifestyle
      counselor to set calorie and physical activity goals and to discuss behavioral
      strategies at baseline, 6 and 12 months. During the first year, enhanced
      intervention participants receive monthly counseling phone calls to assist in
      attaining and maintaining their goals. Enhanced intervention participants also
      receive weekly mailings consisting of tailored and non-tailored print materials
      and videos focusing on weight loss, physical activity promotion and healthy
      eating. The second year focuses on maintenance with enhanced intervention
      participants receiving tailored and non-tailored print materials and videos
      regularly throughout the year. Standard intervention participants receive five
      informational handouts on weight loss across the two years. This enhanced
      intervention that consists of multiple modalities of print, telephone, and video
      with limited face-to-face counseling holds promise for being effective for
      encouraging weight loss, increasing physical activity and healthy eating, and
      also for being cost effective and generalizable for wide clinical use. This study
      will fill an important gap in our knowledge regarding the translation and
      dissemination of research from efficacy studies to best practices in clinical
      settings.

PMID- 24937019
TI  - Conducting qualitative research within Clinical Trials Units: avoiding potential
      pitfalls.
AB  - The value of using qualitative research within or alongside randomised controlled
      trials (RCTs) is becoming more widely accepted. Qualitative research may be
      conducted concurrently with pilot or full RCTs to understand the feasibility and
      acceptability of the interventions being tested, or to improve trial conduct.
      Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of
      RCTs and, increasingly, manage the qualitative research or collaborate with
      qualitative researchers external to the CTU. CTUs are beginning to explicitly
      manage the process, for example, through the use of standard operating procedures
      for designing and implementing qualitative research with trials. We reviewed the
      experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of
      conducting qualitative research concurrently with RCTs. Drawing on experiences
      gained from 15 studies, we identify the potential for the qualitative research to
      undermine the successful completion or scientific integrity of RCTs. We show that
      potential problems can arise from feedback of interim or final qualitative
      findings to members of the trial team or beyond, in particular reporting
      qualitative findings whilst the trial is on-going. The problems include: We make
      recommendations for improving the management of qualitative research within CTUs.

PMID- 24937017
TI  - Strategies and Opportunities to STOP Colon Cancer in Priority Populations: design
      of a cluster-randomized pragmatic trial.
AB  - BACKGROUND: Colorectal cancer is the second-leading cause of cancer deaths in the
      United States. The Strategies and Opportunities to Stop Colorectal Cancer (STOP
      CRC) in Priority Populations study is a pragmatic trial and a collaboration
      between two research institutions and a network of more than 200 safety net
      clinics. The study will assess the effectiveness of a system-based intervention
      designed to improve the rates of colorectal-cancer screening using fecal
      immunochemical testing (FIT) in federally qualified health centers in Oregon and
      Northern California. MATERIAL AND METHODS: STOP CRC is a cluster-randomized
      comparative-effectiveness pragmatic trial enrolling 26 clinics. Clinics will be
      randomized to one of two arms. Clinics in the intervention arm (1) will use an
      automated, data-driven, electronic health record-embedded program to identify
      patients due for colorectal screening and mail FIT kits (with pictographic
      instructions) to them; (2) will conduct an improvement process (e.g. Plan-Do
      Study-Act) to enhance the adoption, reach, and effectiveness of the program.
      Clinics in the control arm will provide opportunistic colorectal-cancer screening
      to patients at clinic visits. The primary outcomes are: proportion of age- and
      screening-eligible patients completing a FIT within 12months; and cost, cost
      effectiveness, and return on investment of the intervention. CONCLUSIONS: This
      large-scale pragmatic trial will leverage electronic health record information
      and existing clinic staff to enroll a broad range of patients, including many
      with historically low colorectal-cancer screening rates. If successful, the
      program will provide a model for a cost-effective and scalable method to raise
      colorectal-cancer screening rates.

PMID- 24937018
TI  - Testing the efficacy of yoga as a complementary therapy for smoking cessation:
      design and methods of the BreathEasy trial.
AB  - INTRODUCTION: Smokers trying to quit encounter many challenges including nicotine
      withdrawal symptoms, cigarette craving, increased stress and negative mood and
      concern regarding weight gain. These phenomena make it difficult to successfully
      quit smoking. Studies in non-smoking populations show that yoga reduces stress
      and negative mood and improves weight control. By increasing mindfulness we
      anticipate that yoga may also improve smokers' ability to cope with the negative
      symptoms associated with quitting. Yoga may also improve cognitive deliberation
      which is needed to make effective choices and avoid smoking in tempting
      situations. METHODS/DESIGN: The BreathEasy study is a rigorous, randomized
      controlled clinical trial examining the efficacy of Iyengar yoga as a
      complementary therapy to cognitive-behavioral therapy for smoking cessation. All
      participants are given an 8-week program of smoking cessation classes, and are
      randomized to either twice weekly yoga (Yoga) or twice-weekly health and wellness
      classes which serve as a control for contact and participant burden (CTL).
      Assessments are conducted at baseline, 8 weeks, 3, 6, and 12 months of follow-up.
      The primary outcome is prolonged abstinence using an intention-to-treat approach.
      Multiple internal and external audits using blind data collection are employed to
      ensure treatment fidelity and reliability of study results. To understand why
      yoga may be more effective than CTL, we will examine the mechanisms of action
      (i.e., mediators) underlying intervention efficacy. We will examine the
      maintenance of yoga practice and smoking status at each follow-up. Focus groups
      and interviews will be used to enrich our understanding of the relationship of
      yoga practice and smoking abstinence. CONCLUSIONS: This study will provide a
      stringent test of the relative efficacy of yoga compared to a condition that
      controls for contact time and attention. The use of mixed methodology also
      provides the opportunity to validate existing knowledge about yoga and helps to
      explore new themes for future mindfulness and yoga research.

PMID- 24937020
TI  - Treatment with baicalein attenuates methionine-choline deficient diet-induced non
      alcoholic steatohepatitis in rats.
AB  - Baicalein, a naturally occurring flavone, has been proved as a promising
      chemopreventive compound for many chronic human diseases. The aim of this work
      was to investigate whether treatment with baicalein prevented nonalcoholic
      steatohepatitis (NASH) induced by methionine-choline-deficient (MCD) diet. Rats
      were divided into four experimental groups and fed for 8 weeks as follows: (1)
      control rats; (2) control rats treated with baicalein (intraperitoneal injection
      of 10mg/kg); (3) MCD-diet-fed rats; (4) MCD-diet-fed rats treated with baicalein.
      Treatment with baicalein prevented MCD-diet-induced NASH, as evidenced by reduced
      histological scores, apoptosis, activities of ALT and AST, and hepatic fat
      accumulation in rats. Treatment with baicalein abated MCD-diet-induced oxidative
      stress through enhancing Nrf2/HO-1 pathway and activities of SOD and catalase in
      livers. Treatment with baicalein preserved hepatic mitochondrial function in MCD
      diet fed rats. Treatment with baicalein reduced hepatic NO formation through
      suppressing MCD-diet-induced iNOS activation, and suppressed MCD-diet-induced
      inflammation through suppressing NFkappaB activation and reducing IL-6 and
      TNFalpha expressions in livers. Treatment of MCD-diet fed rats with baicalein had
      a beneficial modulation on expression profiles of fatty acid metabolism genes in
      livers. The results support the investigation of baicalein as a therapeutic
      candidate for NASH induced by MCD diet in rats. 

PMID- 24937021
TI  - Benzyl butyl phthalate exposure impairs learning and memory and attenuates
      neurotransmission and CREB phosphorylation in mice.
AB  - The existing data are insufficient to evaluate the neurotoxicity of benzyl butyl
      phthalate (BBP) exposure on the brain, and the underlying mechanisms to explain
      these effects remain unclear. Kun Ming (KM) mice were exposed to BBP (0, 50, 250,
      1250 mg/kg) via gavage for 14 days. Employing the Morris water maze (MWM) test,
      we observed that mice demonstrated poorer learning and memory performance than
      the control group at doses of 250 and 1250 mg/kg/day. Reduction of locomotor
      activity in mice and depression were indicated by a long "dead time" in the
      Forced Swim Test and tail suspension test. Pathological alterations and oxidative
      damage to the hippocampus were found. To study the molecular mechanisms
      underlying BBP toxicity, the neurotransmitter serotonin (5-hydroxytryptamine, 5
      HT) and pCREB were tested. The modified levels of 5-HT in the hippocampus and the
      decreased levels of CREB phosphorylation after BBP exposure suggested a potential
      mechanism underlying BBP toxicity. We hypothesize that BBP exposure causes a
      decrease in the number of neurotransmitters, which in turn down regulates the
      levels of CREB phosphorylation by the cAMP/protein kinase A (PKA)-mediated
      signaling. The results are an attenuation of the effects of CREB downstream,
      oxidative damage and impaired behavioral performance.

PMID- 24937022
TI  - Iron oxide nanoparticles mediated cytotoxicity via PI3K/AKT pathway: role of
      quercetin.
AB  - Recently Fe2O3 NPs (iron oxide nanoparticles) have been extensively used in
      medical imaging and in industry also. As a result, people are increasingly
      exposed day by day to those nanoparticles. The adverse effect of Fe2O3 NPs is not
      so significant at lower doses but at higher doses Fe2O3 NPs causes significant
      damage to cells. The present study investigates the cell signaling mechanism of
      Fe2O3 NPs induced oxidative stress and cytotoxicity in vitro using murine
      hepatocytes as the working model. In addition, the cytoprotective action of
      quercetin in this pathophysiology has also been investigated. Dose-dependent
      studies suggest that incubation of hepatocytes with 250 MUg/ml Fe2O3 NPs for 4h
      significantly decreased the cell viability and intra-cellular antioxidant
      ability. This study also showed that exposure to Fe2O3 NPs caused hepatocytes
      death via apoptotic pathway. Incubation of hepatocytes with quercetin (50
      MUmol/L) prior to 1h of Fe2O3 NPs exposure protects the cells from the altering
      activities of antioxidant indices, cytotoxicity and apoptotic death. Results
      suggest that Fe2O3 NPs induced cellular damage and quercetin plays a protective
      role in Fe2O3 NPs induced cytotoxicity and apoptotic death.

PMID- 24937023
TI  - Electrochemical stimulation of microbial roxarsone degradation under anaerobic
      conditions.
AB  - Roxarsone (4-hydroxy-3-nitrophenylarsonic acid) has been commonly used in animal
      feed as an organoarsenic additive, most of which is excreted in manure. Roxarsone
      is easily biodegraded to 4-hydroxy-3-aminophenylarsonic acid (HAPA) under
      anaerobic conditions, but HAPA persists for long periods in the environment,
      increasing the risk of arsenic contamination through diffusion. We investigated
      the electrochemical stimulation of the microbial degradation of roxarsone under
      anaerobic conditions. After the carbon sources in the substrate were depleted,
      HAPA was slowly degraded to form arsenite under anaerobic conditions. The
      degradation rate of HAPA was significantly increased when 0.5 V was applied
      without adding a carbon source. The two-cell membrane reactor assays reveal that
      the HAPA was degraded in the anode chambers, confirming that the anode enhanced
      the electron transfer process by acting as an electron acceptor. The degradation
      product formed with electrochemical stimulation was arsenate, which facilitates
      the removal of arsenic from wastewater. Based on the high performance liquid
      chromatography-ultraviolet-hydride generation-atomic fluorescence spectrometry
      (HPLC-UV-HG-AFS) and gas chromatography-mass spectrometry (GC-MS) data, the
      pathway for the biodegradation of roxarsone and the mechanisms for the
      electrochemically stimulated degradation are proposed. This method provides a
      potential solution for the removal of arsenic from organoarsenic-contaminated
      wastewater. 

PMID- 24937024
TI  - Effects of physical exercise on health-related quality of life and blood lipids
      in perimenopausal women: a randomized placebo-controlled trial.
AB  - OBJECTIVE: This study aims to evaluate the treatment effects of physical exercise
      on menopausal symptoms in middle-aged female medical staff experiencing
      perimenopausal syndrome. METHODS: A total of 157 female medical staff aged 40 to
      55 years and with a Kupperman index score of 15 points or higher were randomized
      1:1 into an intervention group (n = 78) or a control group (n = 79). Women in the
      intervention group were asked to perform aerobic physical exercise (walking with
      strides) three times a week or more, whereas those in the control group continued
      as normal. Measurements were taken at baseline and on weeks 4, 8, and 12, with
      total Kupperman index score, scores on individual elements of the scale, weight,
      and waist circumference recorded. In addition, fasting blood glucose,
      triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low
      density lipoprotein cholesterol were recorded at baseline and on week 12. The
      effects of physical exercise therapy on perimenopausal syndrome were evaluated by
      comparing changes in these parameters between the control group and the
      intervention group. RESULTS: Fifty-four and 57 women completed all three follow
      ups in the intervention and control groups, respectively. On week 12, the mean
      (SD) change in total Kupperman index score (-9.23 [6.23]) from baseline to week
      12; the mean (SD) changes in individual scores for paresthesia (-1.08 [1.51]),
      insomnia (-1.00 [1.46]), irritability (-1.00 [1.34]), joint or muscle pain (-0.75
      [0.74]), fatigue (-0.56 [0.75]), headache (-0.54 [0.75]), formication (-0.38
      [0.66]), and sexual life (-0.62 [1.71]); and the mean (SD) changes in total
      cholesterol (-0.76 [0.63] mmol/L) and triglycerides (-0.20 [0.50] mmol/L) were
      significantly higher in the intervention group than in the control group (P <
      0.05). In the intervention group, total Kupperman index score, weight, body mass
      index, waist circumference, triglycerides, and total cholesterol were
      significantly lower on week 12 compared with baseline (P < 0.05). CONCLUSIONS:
      Physical exercise can substantially reduce menopausal symptoms and improve blood
      lipid status and body weight.

PMID- 24937026
TI  - Complication of a 2-mg estradiol vaginal ring: fibrotic vaginal adhesion.
AB  - OBJECTIVE: This work aims to review a novel case of a retained 2-mg estradiol
      vaginal ring used to treat postmenopausal urogenital atrophy. The ring was found
      adhered to the posterior fornix by a fibrotic band. This is the first reported
      case in the medical literature. METHODS: We describe the case of a postmenopausal
      woman experiencing symptoms of urogenital atrophy. Factors predisposing her to
      this complication (such as inconsistent use of other forms of vaginal estradiol,
      initial incorrect use of the ring with two rings in place, and subsequent vaginal
      stenosis and irritation requiring vaginal dilator therapy at one point in her
      treatment course) were analyzed. A review of the medical literature was performed
      to examine the safety profile of estradiol vaginal rings used to treat urogenital
      atrophy and to investigate the incidence of complications. RESULTS: Two-milligram
      estradiol vaginal rings treat symptoms of urogenital atrophy by delivering a
      constant supply of estradiol to the vaginal epithelium. The ring has been shown
      to be as safe and effective as other forms of vaginal estrogen. Vaginal
      irritation is a known complication of 2-mg estradiol vaginal rings and other
      vaginal implants; however, none of the randomized controlled trials that have
      compared the ring to other vaginal estrogen forms have reported adherence of the
      ring to the vaginal epithelium. CONCLUSIONS: Providers should be aware of the
      possibility of ring adherence to the vaginal epithelium and should exercise
      caution in using the 2-mg estradiol vaginal ring in women with significant
      vaginal stenosis or irritation.

PMID- 24937025
TI  - Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium
      supplementation in older women.
AB  - OBJECTIVE: This study aims to prospectively assess the incidence of
      hypercalciuria and hypercalcemia with different doses of vitamin D and with a
      calcium intake of approximately 1,200 mg/day. METHODS: This was a 1-year
      randomized placebo-controlled study of vitamin D (400-4,800 IU/d) in 163 white
      women aged 57 to 90 years. Calcium citrate tablets (200 mg) were added to the
      diet to achieve a total calcium intake of approximately 1,200 mg/day in all
      groups. All women had vitamin D insufficiency at baseline, with serum 25
      hydroxyvitaminD levels lower than 20 ng/mL (50 nmol/L). Serum and 24-hour urine
      calcium were collected every 3 months on supplementation, any test result above
      the upper reference range represented an episode of hypercalcemia or
      hypercalciuria. Mixed-effects models and multivariate logistic regression were
      used in the analysis. RESULTS: Hypercalcemia (>10.2 mg/dL [2.55 mmol/L]) occurred
      in 8.8% of white women. Hypercalciuria (>300 mg/d [7.5 mmol]) occurred in 30.6%
      of white women. Episodes of hypercalciuria were transient in half of the group
      and recurrent in the other half. No relationship between hypercalcemia or
      hypercalciuria and vitamin D dose was found, and hypercalciuria was equally
      common in the placebo group. CONCLUSIONS: Hypercalciuria and hypercalcemia
      commonly occur with vitamin D and calcium supplements. Whether hypercalciuria and
      hypercalcemia are caused by calcium, vitamin D, or both is unclear. These
      findings may have relevance to the reported increase in kidney stones in the
      Women's Health Initiative trial. Because calcium 1,200 mg and vitamin D 800
      IU/day are widely recommended in postmenopausal women, systematic evaluation of
      the safety of supplements is warranted in clinical management and in future
      studies.

PMID- 24937027
TI  - Concurrent use of statins and hormone therapy and risk of venous thromboembolism
      in postmenopausal women: a population-based case-control study.
AB  - OBJECTIVE: Statins and hormone therapy (HT), often used concurrently in
      postmenopausal women, have antagonist effects on the risk of venous
      thromboembolism (VTE). This study aims to determine whether statins attenuate the
      increased VTE risk associated with HT. METHODS: We conducted a nested case
      control study within a population-based cohort of women aged 50 to 79 years
      between January 1, 1987 and March 1, 2008, who were identified from the UK
      General Practice Research Database. Cases of VTE occurring during follow-up were
      identified and each matched with up to 10 controls from the cohort. Odds ratios
      (ORs) for the effects of concurrent HT and statin use on the risk of VTE were
      estimated using conditional logistic regression with interaction terms. RESULTS:
      The cohort included 955,582 postmenopausal women, with 23,505 cases of VTE
      matched with 231,562 controls. Regardless of any HT use, current use of statins
      was associated with a decreased risk of VTE (OR, 0.83; 95% CI, 0.78-0.87). The
      interaction between statin use and HT use was of borderline significance (P =
      0.053). Consequently, among nonusers of statins, the risk of VTE was elevated
      with current use of oral estrogen and progestogen combinations (OR, 1.55; 95% CI,
      1.45-1.66) but this risk was not elevated among users of statins (OR, 0.98; 95%
      CI, 0.56-1.73). There was no such modification of the OR with statins and other
      HT types and formulations. CONCLUSIONS: Statins could potentially attenuate the
      increased risk associated with HT combinations of oral estrogens and
      progestogens. This observation needs further confirmation in other large cohorts.

PMID- 24937028
TI  - Response to letter to the editor.

PMID- 24937029
TI  - Letter to the editor.

PMID- 24937030
TI  - Hormone therapy and hemostasis among postmenopausal women: a review.
AB  - OBJECTIVE: Postmenopausal hormone therapy (HT), which consists of exogenous
      estrogens with or without combined progestogens, remains the most effective
      treatment of climacteric symptoms. Depending on its characteristics, it may
      nevertheless increase the risk of venous thromboembolism, and its effects on
      hemostasis have been studied for several decades. The aim of this review was to
      summarize current knowledge on the effects of HT on hemostasis, taking into
      account the route of estrogen administration, the daily dose and chemical
      structure of estrogens, and the pharmacologic class of progestogens. METHODS:
      Data from randomized controlled trials that included a control group (either
      placebo or no treatment) were selected, and analysis was conducted on different
      generations of biomarkers. RESULTS: Overall, studies showed a hemostasis
      imbalance among oral estrogen users with a decrease in coagulation inhibitors and
      an increase in markers of activation coagulation, leading to global enhanced
      thrombin generation. By contrast, transdermal estrogen use was associated with
      less change in hemostasis variables and did not activate coagulation and
      fibrinolysis. No clear difference in HT effects on hemostasis was highlighted
      between daily doses of estrogens, between estrogen compounds, and between
      pharmacologic classes of progestogens. CONCLUSIONS: Changes in hemostasis are in
      accordance with clinical results showing an increased thrombotic risk with oral-
      but not transdermal--estrogen use.

PMID- 24937031
TI  - Positive endometrial cultures: pathologic or incidental?

PMID- 24937033
TI  - Association of Connexin37 C1019T with myocardial infarction and coronary artery
      disease: a meta-analysis.
AB  - BACKGROUND: Several studies have reported that Connexin37 (Cx37) gene C1019T
      polymorphism is associated with myocardial infarction (MI) and coronary artery
      disease (CAD). However, the results remain contradictory. METHODS AND RESULTS:
      Pubmed, Embase, and Cochrane library databases were systemically searched. Data
      were extracted by two independent reviewers and pooled odds ratio (OR) with 95%
      confidence interval (CI) was calculated. A total of 3498 MI cases and 3986
      controls, as well as 1808 CAD cases and 1197 controls were enrolled in this meta
      analysis. For MI, the overall ORs and 95% CIs of 1019T were 1.04, 0.95-1.15; and
      1.02, 0.85-1.22 in dominant and recessive models, respectively. For CAD, the
      overall ORs and 95% CIs of 1019T were 0.61, 0.51-0.72; and 0.52, 0.43-0.62 in
      dominant and recessive models, respectively. No publication bias was found in
      this meta-analysis. CONCLUSIONS: This meta-analysis showed that Cx37 C1019T was a
      risk factor for MI and a protective factor for CAD.

PMID- 24937032
TI  - Optimized cryopreservation of mixed microbial communities for conserved
      functionality and diversity.
AB  - The use of mixed microbial communities (microbiomes) for biotechnological
      applications has steadily increased over the past decades. However, these
      microbiomes are not readily available from public culture collections, hampering
      their potential for widespread use. The main reason for this lack of availability
      is the lack of an effective cryopreservation protocol. Due to this critical need,
      we evaluated the functionality as well as the community structure of three
      different types of microbiomes before and after cryopreservation with two
      cryoprotective agents (CPA). Microbiomes were selected based upon relevance
      towards applications: (1) a methanotrophic co-culture (MOB), with potential for
      mitigation of greenhouse gas emissions, environmental pollutants removal and
      bioplastics production; (2) an oxygen limited autotrophic
      nitrification/denitrification (OLAND) biofilm, with enhanced economic and
      ecological benefits for wastewater treatment, and (3) fecal material from a human
      donor, with potential applications for fecal transplants and pre/probiotics
      research. After three months of cryopreservation at -80  degrees C, we found that
      metabolic activity, in terms of the specific activity recovery of MOB, aerobic
      ammonium oxidizing bacteria (AerAOB) and anaerobic AOB (AnAOB, anammox) in the
      OLAND mixed culture, resumes sooner when one of our selected CPA [dimethyl
      sulfoxide (DMSO) and DMSO plus trehalose and tryptic soy broth (DMSO+TT)] was
      added. However, the activity of the fecal community was not influenced by the CPA
      addition, although the preservation of the community structure (as determined by
      16S rRNA gene sequencing) was enhanced by addition of CPA. In summary, we have
      evaluated a cryopreservation protocol that succeeded in preserving both community
      structure and functionality of value-added microbiomes. This will allow
      individual laboratories and culture collections to boost the use of microbiomes
      in biotechnological applications.

PMID- 24937035
TI  - Ordered mesoporous black TiO(2) as highly efficient hydrogen evolution
      photocatalyst.
AB  - Mesoporous TiO2 has gained increasing interest because of its outstanding
      properties and promising applications in a wide range of fields. Herein, we
      report the facile synthesis of ordered mesoporous black TiO2 (OMBT) materials,
      which exhibit excellent photocatalytic hydrogen evolution performances. In this
      case, the employment of a thermally stable and high-surface-area mesoporous TiO2
      as the hydrogenation precursor is the key for fabricating the OMBT materials,
      which not only facilitate H2 gas diffusion into TiO2 and interaction with their
      structures but also maintain the ordered mesoporous structures as well as inhibit
      the phase transformation (from anatase to rutile) and crystal growth during
      hydrogenation at 500  degrees C. The resultant OMBT materials possess a
      relatively high surface area of ~124 m(2) g(-1) and a large pore size and pore
      volume of ~9.6 nm and 0.24 cm(3) g(-1), respectively. More importantly, the OMBT
      materials can extend the photoresponse from ultraviolet to visible and infrared
      light regions and exhibit a high solar-driven hydrogen production rate (136.2
      MUmol h(-1)), which is almost two times as high as that of pristine mesoporous
      TiO2 (76.6 MUmol h(-1)). 

PMID- 24937034
TI  - The assessment of cognitive impairment suspected of dementia in Polish elderly
      people: results of the population-based PolSenior Study.
AB  - The growing incidence of dementia in ageing societies is a major concern of
      health care organizations. Because of its detrimental influence on the mental and
      functional statuses of elderly people, it leads to increased economic burdens
      caused by the social and financial needs of patients with dementia and their
      caregivers. There has been no data concerning the prevalence of dementia in the
      elderly in the general Polish community so far. The main aim of the study was to
      assess the prevalence of cognitive impairment suspected of dementia among the
      Polish elderly and the relationships between cognitive performance and age,
      gender, place of residence and educational status. The presented data was the
      result of nationwide, multicentre PolSenior Study conducted from 2007 to 2011 in
      the Polish elderly population. Cognitive functions were evaluated using Mini
      Mental State Examination (MMSE) performed by pre-trained nurses. The result of
      MMSE lower than 24 points was classified as cognitive impairment suspected of
      dementia and divided according to its severity into three stages: mild, moderate
      and severe dementia. The results were analysed in two ways: raw MMSE and MMSE
      scores after Mungas adjustment (MMSEadj), that is, corrected for age and
      educational level, and these were compared. To verify the suspicion of dementia
      an assessment was complemented by an interview of carers for the occurrence and
      course of memory disorders, treatment of dementia and by functional status
      assessment. In order to assess the prevalence of suspicion of dementia in the
      general Polish population, statistical analyses based on weighting were done. The
      suspicion of dementia on the basis of raw MMSE was made in 20.4% of respondents
      aged 65years and more, and after Mungas adjustment in 12.1% of older subjects.
      The prevalence of cognitive impairment grew with increasing age, as well as
      depending on the educational status of elderly respondents in both types of
      analyses; raw MMSE and MMSEadj. There was no significant difference in the
      prevalence of cognitive impairment according to gender in the general population
      (raw MMSE); however in analyses including MMSEadj results, the suspicion of
      dementia was made more often among men. Suspicion of dementia based on raw MMSE
      and MMSEadj results was made significantly more often among men than women at the
      age of 65-69years, and significantly more often among the oldest women, aged
      90years and more. Suspicion of dementia was diagnosed more often in respondents
      living in rural communities (based on raw MMSE, but not on MMSEadj), which might
      be related to the differences in their educational status. 

PMID- 24937036
TI  - Hantaviruses induce antiviral and pro-inflammatory innate immune responses in
      astrocytic cells and the brain.
AB  - Although hantaviruses are not generally considered neurotropic, neurological
      complications have been reported occasionally in patients with hemorrhagic fever
      renal syndrome (HFRS). In this study, we analyzed innate immune responses to
      hantavirus infection in vitro in human astrocytic cells (A172) and in vivo in
      suckling ICR mice. Infection of A172 cells with pathogenic Hantaan virus (HTNV)
      or a novel shrew-borne hantavirus, known as Imjin virus (MJNV), induced
      activation of antiviral genes and pro-inflammatory cytokines/chemokines. MicroRNA
      expression profiles of HTNV- and MJNV-infected A172 cells showed distinct changes
      in a set of miRNAs. Following intraperitoneal inoculation with HTNV or MJNV,
      suckling ICR mice developed rapidly progressive, fatal central nervous system
      associated disease. Immunohistochemical staining of virus-infected mouse brains
      confirmed the detection of viral antigens within astrocytes. Taken together,
      these findings suggest that the neurological findings in HFRS patients may be
      associated with hantavirus-directed modulation of innate immune responses in the
      brain.

PMID- 24937038
TI  - Artificial pancreas: fuzzy logic and control of glycemia.
AB  - PURPOSE OF REVIEW: This review describes the latest efforts, challenges, and
      experience of using automated insulin delivery systems at outpatient settings and
      home studies. This is an important step in getting recognition of these systems
      as a routine therapy for patients with type 1 diabetes. RECENT FINDINGS: Almost 3
      years elapsed since the first description of closed-loop use outside the
      protecting environment of the hospital, at a diabetes camp. In this period,
      several different approaches of closed-loop systems were used at outpatient
      settings. The low-glucose suspend feature on the pump showed a reduction in the
      risk of nocturnal hypoglycemia. Closed-loop systems with diverse control
      algorithms with a single or bihormonal approach showed an improvement in glycemic
      control. The improvement was demonstrated during the overnight use and during the
      24-h use. The outpatient studies with closed-loop systems, especially overnight
      at home, demonstrated that the current configurations are already safe and
      efficient for daily use. Technological advancement should undoubtedly lead to
      even better performance. SUMMARY: Studies using closed-loop systems at patients'
      home are currently being carried out. The preliminary results of these
      experiments are encouraging and enhance our confidence in this tool as suitable
      for use in clinical daily practice.

PMID- 24937037
TI  - Biomarkers in type 1 diabetes: application to the clinical trial setting.
AB  - PURPOSE OF REVIEW: Biomarkers of type 1 diabetes (T1D) are important for
      assessing risk of developing disease, monitoring disease progression, and
      determining responses to clinical treatments. Here we review recent advances in
      the development of biomarkers of T1D with a focus on their utility in clinical
      trials. RECENT FINDINGS: Measurements of autoantibodies and metabolic outcomes
      have been the foundation of monitoring T1D for the past 20 years. Recent
      advancements have led to improvements in T-cell-specific assays that have been
      used in large-scale clinical trials to measure antigen-specific T cell responses.
      Additionally, new tools are being developed for the measurement of beta cell mass
      and death that will allow for more direct measurement of disease activity.
      Lastly, recent studies have used both immunologic and nonimmunologic biomarkers
      to identify responders to treatments in clinical trials. SUMMARY: Use of
      biomarkers in the study of T1D has largely not changed over the past 20 years;
      however, recent advancements in the field are establishing new techniques that
      allow for more precise monitoring of disease progression. These new tools will
      ultimately lead to an improvement in understanding of disease and will be
      utilized in clinical trials.

PMID- 24937040
TI  - Unresolved controversies in gestational diabetes: implications on maternal and
      infant health.
AB  - PURPOSE OF REVIEW: Gestational diabetes mellitus (GDM) is a major public health
      concern because of rising rates and offspring consequences; yet, expert panels
      are in complete disagreement on how to diagnose and optimally treat GDM. This
      review underscores why there remains no diagnostic standard, no agreement on
      whether excess dietary carbohydrate or fat should be reduced, and whether oral
      hypoglycemic therapy is safe given the unknown offspring effects on hepatic,
      pancreatic, or fat development. RECENT FINDINGS: New diagnostic criteria proposed
      by the American Diabetes Association would triple the prevalence of GDM (~18%).
      Whether the treatment of women with these milder degrees of hyperglycemia will
      improve pregnancy outcomes is unknown given the powerful effect of obesity alone
      on excess fetal growth. There are data that restricting carbohydrate in the diet
      by substituting fat to blunt postprandial glucose levels may worsen maternal
      insulin resistance and that metformin may increase offspring subcutaneous fat.
      SUMMARY: The adoption of the new American Diabetes Association diagnostic
      criteria for GDM was rejected by ACOG and not endorsed by the NIH. Yet, varying
      criteria are used by different centers resulting in confusion for both patient
      care and research. Both maternal diet and agents that cross the placenta could
      potentially modify offspring gene expression. Better identification and treatment
      of mothers and fetuses at risk may have far-reaching implications for maternal
      and child health.

PMID- 24937039
TI  - Changing perspectives in pre-existing diabetes and obesity in pregnancy: maternal
      and infant short- and long-term outcomes.
AB  - PURPOSE OF REVIEW: Climbing obesity rates in women have propelled the increasing
      prevalence of type 2 diabetes mellitus (T2DM) in pregnancy, and an increasing
      number of women with type 1 diabetes mellitus (T1DM) are also affected by
      obesity. Increasing recognition that an intrauterine environment characterized by
      obesity, insulin resistance, nutrient excess, and diabetes may be fueling the
      obesity epidemic in children has created enormous pressure to re-examine the
      conventional wisdom of our current approaches. RECENT FINDINGS: Compelling data
      in pregnancies complicated by diabetes, in particular those accompanied by
      insulin resistance and obesity, support a fetal programming effect resulting in
      increased susceptibility to metabolic disease for the offspring later in life.
      Recent data also underscore the contribution of obesity, lipids, and lesser
      degrees of hyperglycemia on fetal fat accretion, challenging the wisdom of
      current gestational weight gain recommendations with and without diabetes. The
      risks of adverse pregnancy outcomes in T2DM are at least as high as in T1DM and
      there remains controversy about the ideal glucose treatment targets, the benefit
      of different insulin analogues, and the role of continuous glucose monitoring in
      T1DM and T2DM. SUMMARY: It has become unmistakably evident that achieving optimal
      outcomes in mothers with diabetes is clearly impacted by ideal glycemic control
      but goes far beyond it. The intrauterine metabolic environment seems to have long
      term implications on the future health of the offspring so that the effectiveness
      of our current approaches can no longer be simply measured by whether or not
      maternal glucose values are at goal.

PMID- 24937041
TI  - Metabolic effects of sleep disruption, links to obesity and diabetes.
AB  - PURPOSE OF REVIEW: To highlight the adverse metabolic effects of sleep disruption
      and to open ground for research aimed at preventive measures. This area of
      research is especially relevant given the increasing prevalence of voluntary
      sleep curtailment, sleep disorders, diabetes, and obesity. RECENT FINDINGS:
      Epidemiological studies have established an association between decreased self
      reported sleep duration and an increased incidence of type 2 diabetes (T2D),
      obesity, and cardiovascular disease. Experimental laboratory studies have
      demonstrated that decreasing either the amount or quality of sleep decreases
      insulin sensitivity and decreases glucose tolerance. Experimental sleep
      restriction also causes physiological and behavioral changes that promote a
      positive energy balance. Although sleep restriction increases energy expenditure
      because of increased wakefulness, it can lead to a disproportionate increase in
      food intake, decrease in physical activity, and weight gain. SUMMARY: Sleep
      disruption has detrimental effects on metabolic health. These insights may help
      in the development of new preventive and therapeutic approaches against obesity
      and T2D based on increasing the quality and/or quantity of sleep.

PMID- 24937042
TI  - A new silver nanorod SPR probe for detection of trace benzoyl peroxide.
AB  - The stable silver nanorod (AgNR) sol in red was prepared by the two-step
      procedure of NaBH4-H2O2 and citrate heating reduction. The AgNR had a transverse
      and a longitudinal surface plasmon resonance (SPR) absorption peak at 338 nm and
      480 nm. Meanwhile, two transverse and longitudinal SPR Rayleigh scattering (SPR
      RS) peaks at 340 nm and 500 nm were observed firstly using common fluorescence
      spectrometer. The SPR absorption, RS, surface enhanced Raman scattering (SERS)
      and electron microscope technology were used to study the formation mechanism of
      red silver nanorods and the SERS enhancement mechanism of nano-aggregation. The
      AgNR-BPO SPR absorption and AgNR-NaCl-BPO SPR-RS analytical systems were studied
      to develop two new simple, rapid, and low-cost SPR methods for the detection of
      trace BPO.

PMID- 24937043
TI  - Optimal dielectric and cavity configurations for improving the efficiency of
      electron paramagnetic resonance probes.
AB  - An electron paramagnetic resonance (EPR) spectrometer's lambda efficiency
      parameter (Lambda) is one of the most important parameters that govern its
      sensitivity. It is studied for an EPR probe consisting of a dielectric resonator
      (DR) in a cavity (CV). Expressions for Lambda are derived in terms of the probe's
      individual DR and CV components, Lambda1 and Lambda2 respectively. Two important
      cases are considered. In the first, a probe consisting of a CV is improved by
      incorporating a DR. The sensitivity enhancement depends on the relative rather
      than the absolute values of the individual components. This renders the analysis
      general. The optimal configuration occurs when the CV and DR modes are nearly
      degenerate. This configuration guarantees that the probe can be easily coupled to
      the microwave bridge while maintaining a large Lambda. It is shown that for a
      lossy CV with a small quality factor Q2, one chooses a DR that has the highest
      filling factor, eta1, regardless of its Lambda1 and Q1. On the other hand, if the
      CV has a large Q2, the optimum DR is the one which has the highest Lambda1. This
      is regardless of its eta1 and relative dielectric constant, Er. When the quality
      factors of both the CV and DR are comparable, the lambda efficiency is reduced by
      a factor of 2. Thus the signal intensity for an unsaturated sample is cut in
      half. The second case is the design of an optimum shield to house a DR. Besides
      preventing radiation leakage, it is shown that for a high loss DR, the shield can
      actually boost Lambda above the DR value. This can also be very helpful for
      relatively low efficiency dielectrics as well as lossy samples, such as polar
      liquids. 

PMID- 24937044
TI  - Effects of ageing and soil properties on the oral bioavailability of
      benzo[a]pyrene using a swine model.
AB  - Oral bioavailability of benzo[a]pyrene (B[a]P) was studied in a swine model using
      eight spiked soil samples after incubation for 50 and/or 90 days. Silica sand was
      used as a reference material and the relative bioavailability (RB) of B[a]P in
      soils was calculated as the quotient of the area under the plasma B[a]P curve
      (AUC) for soil and AUC for the silica sand. Significantly reduced RB was observed
      in all study soils after 90 days ageing, ranging from 22.1+/-0.4% to 62.7+/
      10.1%, except for one very sandy soil (sand content 87.6%) where RB was unchanged
      (108.1+/-8.0%). Apart from this, bioavailability decreased during ageing with the
      decrease (from day 50 to day 90) being only significant for a clayey soil
      containing expandable clay minerals. Statistical analyses of B[a]P RB at day 90
      (eight soils) and soil properties showed no direct correlation between RB and
      specific soil properties such as total organic carbon (TOC) and clay content
      which were commonly linked to organic contaminant sequestration. However,
      strongly significant relationships (p<0.001) were found between RB and the fine
      particle associated carbon (FPAC) defined as (Silt+Clay)/TOC, and between RB and
      the soil mesopore (<6nm; p<0.001) fraction, after two samples with high pH and
      high EC being excluded from the analyses. The bioaccessibility estimated by four
      in vitro extraction methods: dichloromethane/acetone sonication (DCM/Ace),
      butanol vortex (BuOH), hydroxypropyl-beta-cyclodextrin extraction (HPCD) and
      Milli Q water leaching methods at different sampling time (1 day, 50 days and 90
      days after spiking) also showed a decreasing trend. Significant correlations were
      found between B[a]P RB and DCM/Ace (R(2)=0.67, p<0.05) extractable fraction and
      BuOH (R(2)=0.75, p<0.01) extractable fraction.

PMID- 24937045
TI  - The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival,
      attenuates inflammation and improves functional recovery in mice with traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) is the leading cause of death in young adults in the
      United States, but there is still no effective agent for treatment. N
      arachidonoylethanolamine (anandamide, AEA) is a major endocannabinoid in the
      brain. Its increase after brain injury is believed to be protective. However, the
      compensatory role of AEA is transient due to its rapid hydrolysis by the fatty
      acid amide hydrolase (FAAH). Thus, inhibition of FAAH can boost the endogenous
      levels of AEA and prolong its protective effect. Using a TBI mouse model, we
      found that post-injury chronic treatment with PF3845, a selective and potent FAAH
      inhibitor, reversed TBI-induced impairments in fine motor movement, hippocampus
      dependent working memory and anxiety-like behavior. Treatment with PF3845
      inactivated FAAH activity and enhanced the AEA levels in the brain. It reduced
      neurodegeneration in the dentate gyrus, and up-regulated the expression of Bcl-2
      and Hsp70/72 in both cortex and hippocampus. PF3845 also suppressed the increased
      production of amyloid precursor protein, prevented dendritic loss and restored
      the levels of synaptophysin in the ipsilateral dentate gyrus. Furthermore, PF3845
      suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2
      and enhanced the expression of arginase-1 post-TBI, suggesting a shift of
      microglia/macrophages from M1 to M2 phenotype. The effects of PF3845 on TBI
      induced behavioral deficits and neurodegeneration were mediated by activation of
      cannabinoid type 1 and 2 receptors and might be attributable to the
      phosphorylation of ERK1/2 and AKT. These results suggest that selective
      inhibition of FAAH is likely to be beneficial for TBI treatment. 

PMID- 24937046
TI  - Neuropathic plasticity in the opioid and non-opioid actions of dynorphin A
      fragments and their interactions with bradykinin B2 receptors on neuronal
      activity in the rat spinal cord.
AB  - Dynorphin A is an endogenous opioid peptide derived from the precursor
      prodynorphin. The proteolytic fragment dynorphin A (1-17) exhibits inhibitory
      effects via opioid receptors. Paradoxically, the activity of the dynorphin system
      increases with chronic pain and neuropathy is associated with the up-regulation
      of dynorphin biosynthesis. Dynorphin A (1-17) is cleaved in vivo to produce a non
      opioid fragment, dynorphin A (2-17). Previously, a mechanism by which the non
      opioid fragment promotes pain through agonist action at bradykinin receptors was
      revealed. Bradykinin receptor expression is up-regulated after nerve injury and
      both a truncated version of non-opioid fragment dynorphin A (2-17), referred to
      as 'Ligand 10', and novel bradykinin receptor antagonist 'Ligand 14', are known
      to bind to the bradykinin receptor. Here we show that Ligand 10 facilitates the
      response of wide dynamic range (WDR) neurons to innocuous and noxious mechanical
      stimuli in neuropathic, but not naive, animals, while Ligand 14 exhibits
      inhibitory effects in neuropathic animals only. Furthermore, we reveal an
      inhibitory effect of Ligand 14 in naive animals by pre-dosing with either Ligand
      10 or a 5-HT3 receptor agonist to reflect activation of descending excitatory
      drives. Thus remarkably, by mimicking pro-excitatory pharmacological changes that
      occur after nerve injury in a naive animal, we induce a state whereby the
      inhibitory actions of Ligand 14 are now effective. Ultimately our data support an
      increasing number of studies that suggest that blocking spinal bradykinin
      receptors may have a therapeutic potential in chronic pain states, here, in
      particular, in neuropathic pain. 

PMID- 24937047
TI  - Beneficial effects of thymosin beta4 on spinal cord injury in the rat.
AB  - Thymosin beta4 (Tbeta4) has many physiological functions that are highly relevant
      to spinal cord injury (SCI), including neuronal survival, anti-inflammation,
      wound repair promotion, and angiogenesis. The present study investigated the
      therapeutic value of Tbeta4 in SCI, with a focus on its neuroprotective, anti
      inflammatory, and vasculoprotective properties. Tbeta4 or a saline control was
      administered by intraperitoneal injection 30 min, 3 days, or 5 days after SCI
      with mild compression in rat. Locomotor recovery was tested with the Basso
      Beattie-Bresnahan scale and a footprint analysis. All behavioral assessments were
      markedly improved with Tbeta4 treatment. Histological examination at 7 days post
      injury showed that the numbers of surviving neurons and oligodendrocytes were
      significantly increased in Tbeta4-treated animals compared to saline-treated
      controls. Levels of myelin basic protein, a marker of mature oligodendrocytes, in
      Tbeta4-treated rats were 57.8% greater than those in saline-treated controls. The
      expression of ED1, a marker of activated microglia/macrophages, was reduced by
      36.9% in the Tbeta4-treated group compared to that of the saline-treated group.
      Tbeta4 treatment after SCI was also associated with a significant decrease in pro
      inflammatory cytokine gene expression and a significant increase in the mRNA
      levels of IL-10 compared to the control. Moreover, the size of lesion cavity
      delineated by astrocyte scar in the injured spinal cord was markedly reduced in
      Tbeta4-treated animals compared to saline-treated controls. Given the known
      safety of Tbeta4 in clinical trials and its beneficial effects on SCI recovery,
      the results of this study suggested that Tbeta4 is a good candidate for SCI
      treatment in humans. 

PMID- 24937048
TI  - Severity of chronic experimental Chagas' heart disease parallels tumour necrosis
      factor and nitric oxide levels in the serum: models of mild and severe disease.
AB  - Heart tissue inflammation, progressive fibrosis and electrocardiographic
      alterations occur in approximately 30% of patients infected by Trypanosoma cruzi,
      10-30 years after infection. Further, plasma levels of tumour necrosis factor
      (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction
      in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish
      experimental models that mimic a range of parasitological, pathological and
      cardiac alterations described in patients with chronic Chagas' heart disease and
      evaluate whether heart disease severity was associated with increased TNF and NO
      levels in the serum. Our results show that C3H/He mice chronically infected with
      the Colombian T. cruzi strain have more severe cardiac parasitism and
      inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and
      fibronectin deposition in the heart tissue, increased levels of creatine kinase
      cardiac MB isoenzyme activity in the serum and more severe electrical
      abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6
      mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and
      mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF
      and NO levels in the serum. Therefore, these models are appropriate for studying
      the pathophysiology and biomarkers of CCC progression, as well as for testing
      therapeutic agents for patients with Chagas' heart disease. 

PMID- 24937049
TI  - Tuberculin skin test and interferon-gamma release assay values are associated
      with antimicrobial peptides expression in  polymorphonuclear cells during latent
      tuberculous infection.
AB  - It has been reported that patients with progressive tuberculosis (TB) express
      abundant amounts of the antimicrobial peptides (AMPs) cathelicidin (LL-37) and
      human neutrophil peptide-1 (HNP-1) in circulating cells, whereas latent TB
      infected donors showed no differences when compared with purified protein
      derivative (PPD) and QuantiFERON(r)-TB Gold (QFT)-healthy individuals. The aim of
      this study was to determine whether LL-37 and HNP-1 production correlates with
      higher tuberculin skin test (TST) and QFT values in TB household contacts. Twenty
      six TB household contact individuals between 26-58 years old TST and QFT positive
      with at last two years of latent TB infection were recruited. AMPs production by
      polymorphonuclear cells was determined by flow cytometry and correlation between
      TST and QFT values was analysed. Our results showed that there is a positive
      correlation between levels of HNP-1 and LL-37 production with reactivity to TST
      and/or QFT levels. This preliminary study suggests the potential use of the
      expression levels of these peptides as biomarkers for progression in latent
      infected individuals. 

PMID- 24937050
TI  - Why do forward maskers affect auditory intensity discrimination? Evidence from
      "molecular psychophysics".
AB  - Nonsimultaneous maskers can strongly impair performance in an auditory intensity
      discrimination task. Using methods of molecular psychophysics, we quantified the
      extent to which (1) a masker-induced impairment of the representation of target
      intensity (i.e., increase in internal noise) and (2) a systematic influence of
      the masker intensities on the decision variable contribute to these effects. In a
      two-interval intensity discrimination procedure, targets were presented in quiet,
      and combined with forward maskers. The lateralization of the maskers relative to
      the targets was varied via the interaural time difference. Intensity difference
      limens (DLs) were strongly elevated under forward masking but less with
      contralateral than with ipsilateral maskers. For most listeners and conditions,
      perceptual weights measuring the relation between the target and masker levels
      and the response in the intensity discrimination task were positive and
      significant. Higher perceptual weights assigned to the maskers corresponded to
      stronger elevations of the intensity DL. The maskers caused only a weak increase
      in internal noise, unrelated to target level and masker lateralization. The
      results indicate that the effects of forward masking on intensity discrimination
      are determined by an inclusion of the masker intensities in the decision
      variable, compatible with the hypothesis that the impairment in performance is to
      a large part caused by difficulties in directing selective attention to the
      targets. The effects of masker lateralization are evidence for top-down
      influences, and the observed positive signs of the masker weights suggest that
      the relevant mechanisms are located at higher processing stages rather than in
      the auditory periphery. 

PMID- 24937051
TI  - Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory
      avoidance responses in the elevated T-maze.
AB  - Corticotropin-releasing factor (CRF) plays a critical role in the mediation of
      physiological and behavioral responses to stressors. In the present study, we
      investigated the role played by the CRF system within the dorsomedial
      hypothalamus (DMH) in the modulation of anxiety- and panic-related responses.
      Male Wistar rats were administered into the DMH with CRF (125 and 250 ng/0.2 MUl,
      experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 MUl, experiment
      2) and 10 min later tested in the elevated T-maze (ETM) for inhibitory avoidance
      and escape measurements. In clinical terms, these responses have been
      respectively related to generalized anxiety and panic disorder. To further verify
      if the anxiogenic effects of CRF were mediated by CRFR1 activation, we also
      investigated the effects of the combined treatment with CRF (250 ng/0.2 MUl) and
      antalarmin (25 ng/0.2 MUl) (experiment 3). All animals were tested in an open
      field, immediately after the ETM, for locomotor activity assessment. Results
      showed that 250 ng/0.2MUl of CRF facilitated ETM avoidance, an anxiogenic
      response. Antalarmin significantly decreased avoidance latencies, an anxiolytic
      effect, and was able to counteract the anxiogenic effects of CRF. None of the
      compounds administered altered escape responses or locomotor activity
      measurements. These results suggest that CRF in the DMH exerts anxiogenic effects
      by activating type 1 receptors, which might be of relevance to the
      physiopathology of generalized anxiety disorder.

PMID- 24937052
TI  - The effect of genetic background on behavioral manifestation of Grid2(Lc)
      mutation.
AB  - Mutant mice are commonly used models of hereditary diseases. Nevertheless, these
      mice have phenotypic traits of the original strain, which could interfere with
      the manifestation of the mutation of interest. Lurcher mice represent a model of
      olivocerebellar degeneration, which is caused by the Grid2(Lc) mutation. Lurchers
      show ataxia and various cognitive and behavioral abnormalities. The most commonly
      used strains of Lurcher mice are B6CBA and C3H, but there is no information about
      the role of genetic background on the Grid2(Lc) manifestation. The aim of this
      work was to compare spatial navigation in the Morris water maze, spontaneous
      activity in the open field and motor skills on the horizontal wire, slanted
      ladder and rotarod in B6CBA and C3H Lurcher mutant and wild type mice. The study
      showed impaired motor skills and water maze performance in both strains of
      Lurcher mice. Both C3H Lurcher and C3H wild type mice had poorer performances in
      the water maze task than their B6CBA counterparts. In the open field test, C3H
      mice showed higher activity and lower thigmotaxis. The study showed that genetic
      backgrounds can modify manifestations of the Lurcher mutation. In this case,
      B6CBA Lurcher mice models probably have more validity when studying the
      behavioral aspects of cerebellar degeneration than C3H Lurcher mice, since they
      do not combine abnormalities related to the Grid2(Lc) mutation with strain
      specific problems. 

PMID- 24937053
TI  - Lack of synaptic vesicle protein SV2B protects against amyloid-beta25-35-induced
      oxidative stress, cholinergic deficit and cognitive impairment in mice.
AB  - SV2B is a synaptic protein widely distributed throughout the brain, which is part
      of the complex vesicle protein machinery involved in the regulation of synaptic
      vesicle endocytosis and exocytosis, and therefore in neurotransmitters release.
      The aims of the present work were twofold: (1) phenotype SV2B knockout mice (SV2B
      KO) in a battery of cognitive tests; and (2) examine their vulnerability to
      amyloid-beta25-35 (Abeta25-35) peptide-induced toxicity. SV2B KO mice showed
      normal learning and memory abilities in absence of Abeta25-35 injection. SV2B KO
      mice were protected against the learning deficits induced after icv injection of
      an oligomeric preparation of amyloid-beta25-35 peptide, as compared to wild-type
      littermates (SV2B WT). These mice failed to show Abeta25-35-induced impairments
      in a number of cognitive domains: working memory measured by a spontaneous
      alternation procedure, recognition memory measured by a novel object recognition
      task, spatial reference memory assessed in a Morris water-maze, and long-term
      contextual memory assessed in a inhibitory avoidance task. In addition, SV2B KO
      mice were protected against Abeta25-35-induced oxidative stress and decrease in
      ChAT activity in the hippocampus. These data suggest that SV2B could be a key
      modulator of amyloid toxicity at the synaptic site.

PMID- 24937054
TI  - alpha,epsilon-Hybrid foldamers with 1,2,3-triazole rings: order versus disorder.
AB  - Two epimeric series of foldamers characterized by the presence of a repeating
      alpha,epsilon-dipeptide unit have been prepared and characterized by (1)H NMR and
      ECD spectroscopies together with X-ray diffraction. The first series contains L
      Ala and D-4-carboxy-5-methyl-oxazolidin-2-one (D-Oxd). The other series contains
      L-Ala and L-Oxd. The L,D series of oligomers forms ordered beta-turn foldamers,
      characterized by a 311 pattern. The L,L series is not ordered. Simulations show
      that an ordered L,L trimer lies more than 2 kcal/mol higher than the more stable
      nonfolded extended conformations. Cu(2+) forms complexes with both series but is
      not able to order the L,L series. Analysis of the EPR spectra shows that the L,D
      foldamers bear two types of complexation sites that are assigned as a nitrogen
      donor of the triazole ring and a carboxylate ligand. The L-Ala-D-Oxd-Tri-CO motif
      may be introduced in any peptide sequence requiring the presence of a stable beta
      turn conformations, like in the study of protein-protein interactions.

PMID- 24937055
TI  - The light fantastic.

PMID- 24937064
TI  - DNA metabolism: bases of DNA repair and regulation.

PMID- 24937065
TI  - Neuronal differentiation: 5-HT6R can do it alone.

PMID- 24937066
TI  - Drug monitoring: bright lights yield drug readout.

PMID- 24937067
TI  - Natural strategies for photosynthetic light harvesting.
AB  - Photosynthetic organisms are crucial for life on Earth as they provide food and
      oxygen and are at the basis of most energy resources. They have a large variety
      of light-harvesting strategies that allow them to live nearly everywhere where
      sunlight can penetrate. They have adapted their pigmentation to the spectral
      composition of light in their habitat, they acclimate to slowly varying light
      intensities and they rapidly respond to fast changes in light quality and
      quantity. This is particularly important for oxygen-producing organisms because
      an overdose of light in combination with oxygen can be lethal. Rapid progress is
      being made in understanding how different organisms maximize light harvesting and
      minimize deleterious effects. Here we summarize the latest findings and explain
      the main design principles used in nature. The available knowledge can be used
      for optimizing light harvesting in both natural and artificial photosynthesis to
      improve light-driven production processes. 

PMID- 24937068
TI  - Optogenetic characterization methods overcome key challenges in synthetic and
      systems biology.
AB  - Systems biologists aim to understand how organism-level processes, such as
      differentiation and multicellular development, are encoded in DNA. Conversely,
      synthetic biologists aim to program systems-level biological processes, such as
      engineered tissue growth, by writing artificial DNA sequences. To achieve their
      goals, these groups have adapted a hierarchical electrical engineering framework
      that can be applied in the forward direction to design complex biological systems
      or in the reverse direction to analyze evolved networks. Despite much progress,
      this framework has been limited by an inability to directly and dynamically
      characterize biological components in the varied contexts of living cells.
      Recently, two optogenetic methods for programming custom gene expression and
      protein localization signals have been developed and used to reveal fundamentally
      new information about biological components that respond to those signals. This
      basic dynamic characterization approach will be a major enabling technology in
      synthetic and systems biology. 

PMID- 24937069
TI  - Advances in fluorescence labeling strategies for dynamic cellular imaging.
AB  - Synergistic advances in optical physics, probe design, molecular biology,
      labeling techniques and computational analysis have propelled fluorescence
      imaging into new realms of spatiotemporal resolution and sensitivity. This review
      aims to discuss advances in fluorescent probes and live-cell labeling strategies,
      two areas that remain pivotal for future advances in imaging technology.
      Fluorescent protein- and bio-orthogonal-based methods for protein and RNA imaging
      are discussed as well as emerging bioengineering techniques that enable their
      expression at specific genomic loci (for example, CRISPR and TALENs). Important
      attributes that contribute to the success of each technique are emphasized,
      providing a guideline for future advances in dynamic live-cell imaging. 

PMID- 24937070
TI  - Tracking single molecules at work in living cells.
AB  - Methods for imaging and tracking single molecules conjugated with fluorescent
      probes, called single-molecule tracking (SMT), are now providing researchers with
      the unprecedented ability to directly observe molecular behaviors and
      interactions in living cells. Current SMT methods are achieving almost the
      ultimate spatial precision and time resolution for tracking single molecules,
      determined by the currently available dyes. In cells, various molecular
      interactions and reactions occur as stochastic and probabilistic processes. SMT
      provides an ideal way to directly track these processes by observing individual
      molecules at work in living cells, leading to totally new views of the
      biochemical and molecular processes used by cells whether in signal transduction,
      gene regulation or formation and disintegration of macromolecular complexes. Here
      we review SMT methods, summarize the recent results obtained by SMT, including
      related superresolution microscopy data, and describe the special concerns when
      SMT applications are shifted from the in vitro paradigms to living cells. 

PMID- 24937071
TI  - How to control proteins with light in living systems.
AB  - The possibility offered by photocontrolling the activity of biomolecules in vivo
      while recording physiological parameters is opening up new opportunities for the
      study of physiological processes at the single-cell level in a living organism.
      For the last decade, such tools have been mainly used in neuroscience, and their
      application in freely moving animals has revolutionized this field. New
      photochemical approaches enable the control of various cellular processes by
      manipulating a wide range of protein functions in a noninvasive way and with
      unprecedented spatiotemporal resolution. We are at a pivotal moment where
      biologists can adapt these cutting-edge technologies to their system of study.
      This user-oriented review presents the state of the art and highlights technical
      issues to be resolved in the near future for wide and easy use of these powerful
      approaches. 

PMID- 24937072
TI  - Multifaceted pathways protect human skin from UV radiation.
AB  - The recurrent interaction of skin with sunlight is an intrinsic constituent of
      human life, and exhibits both beneficial and detrimental effects. The apparent
      robust architectural framework of skin conceals remarkable mechanisms that
      operate at the interface between the surface and environment. In this Review, we
      discuss three distinct protective mechanisms and response pathways that safeguard
      skin from deleterious effects of ultraviolet (UV) radiation. The unique
      stratified epithelial architecture of human skin along with the antioxidant
      response pathways constitutes the important defense mechanisms against UV
      radiation. The intricate pigmentary system and its intersection with the immune
      system cytokine axis delicately balance tissue homeostasis. We discuss the
      relationship among these networks in the context of an unusual depigmenting
      disorder, vitiligo. The elaborate tunable mechanisms, elegant multilayered
      architecture and evolutionary selection pressures involved in skin and sunlight
      interaction makes this a compelling model to understand biological complexity. 

PMID- 24937073
TI  - Von Willebrand factor regulation in patients with acute and chronic
      cerebrovascular disease: a pilot, case-control study.
AB  - BACKGROUND AND PURPOSE: In animal models, von Willebrand factor (VWF) is involved
      in thrombus formation and propagation of ischemic stroke. However, the
      pathophysiological relevance of this molecule in humans, and its potential use as
      a biomarker for the risk and severity of ischemic stroke remains unclear. This
      study had two aims: to identify predictors of altered VWF levels and to examine
      whether VWF levels differ between acute cerebrovascular events and chronic
      cerebrovascular disease (CCD). METHODS: A case-control study was undertaken
      between 2010 and 2013 at our University clinic. In total, 116 patients with acute
      ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD,
      and 104 healthy volunteers (HV) were included. Blood was taken at days 0, 1, and
      3 in patients with AIS or TIA, and once in CCD patients and HV. VWF serum levels
      were measured and correlated with demographic and clinical parameters by
      multivariate linear regression and ANOVA. RESULTS: Patients with CCD (158 +/-
      46%) had significantly higher VWF levels than HV (113 +/- 36%, P<0.001), but
      lower levels than AIS/TIA patients (200 +/- 95%, P<0.001). Age, sex, and stroke
      severity influenced VWF levels (P<0.05). CONCLUSIONS: VWF levels differed across
      disease subtypes and patient characteristics. Our study confirms increased VWF
      levels as a risk factor for cerebrovascular disease and, moreover, suggests that
      it may represent a potential biomarker for stroke severity, warranting further
      investigation.

PMID- 24937074
TI  - Toll-like receptor 4 is essential to preserving cardiac function and survival in
      low-grade polymicrobial sepsis.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4), the receptor for endotoxin, mediates
      hyperinflammatory response and contributes to high mortality during both
      endotoxin shock and severe sepsis. However, little is known about the role of
      TLR4 in the pathogenesis of low-grade polymicrobial sepsis, which is often
      associated with immunosuppression. METHODS: Low-grade polymicrobial sepsis was
      generated by cecum ligation and puncture. Mortality was monitored in wild- type
      (C57BL/10ScSn) and TLR4def (C57BL/10ScCr) mice. Ex vivo heart and individual
      cardiomyocyte function were assessed in Langendorff (Hugo Sachs Elektronik;
      Harvard Apparatus, Holliston, MA) and IonOptix systems (IonOptix, Milton, MA),
      respectively. Serum chemistry was tested for liver and kidney injury. Cytokines
      were examined using a multiplex immunoassay. Neutrophil migratory and phagocytic
      functions were assessed using flow cytometry. Reactive oxygen species were
      measured using redox-sensitive dichlorodihydrofluorescein dye. RESULTS: Following
      cecum ligation and puncture, wild-type mice developed bacterial peritonitis with
      mild cardiac dysfunction (n=3 in sham and n=8 in cecum ligation and puncture) and
      a mortality of 23% within 14 days (n=22). In comparison, septic TLR4def mice had
      deleterious cardiac dysfunction (n=6 in sham and n=10 in cecum ligation and
      puncture), kidney and liver injury (n=7), and much higher mortality at 81%
      (n=21). The deleterious effects observed in septic TLR4def mice were associated
      with increased local and systemic cytokine response, reduced neutrophil migratory
      and phagocytic function, increased reactive oxygen species generation in
      leukocytes, and impaired bacterial clearance. CONCLUSION: TLR4 plays an essential
      role in host defense against low-grade polymicrobial sepsis by mediating
      neutrophil migratory/phagocytic functions, attenuating inflammation, reducing
      reactive oxygen species generation, and enhanced bacterial clearance.

PMID- 24937075
TI  - Thoracic epidural anesthesia with ropivacaine does not compromise the tolerance
      of acute normovolemic anemia in pigs.
AB  - BACKGROUND: The initial treatment of an acute blood loss with acellular fluids
      leads to the dilution of the red cell mass remaining in the vasculature, that is,
      to acute normovolemic anemia. Whether the compensation and, thus, the tolerance
      of acute anemia, are affected by sympathetic block induced by thoracic epidural
      anesthesia has not yet been investigated. METHODS: Eighteen anesthetized and
      mechanically ventilated pigs were instrumented with thoracic epidural catheters
      and randomly assigned to receive an epidural injection of either 5-ml ropivacaine
      0.2% (n = 9) aiming for a Th5-Th10 block or saline (n = 9) followed by continuous
      epidural infusion of 5 ml/h of either fluid. Subsequently, acute normovolemic
      anemia was induced by replacement of whole blood with 6% hydroxyethyl starch
      solution until a "critical" limitation of oxygen transport capacity was reached
      as indicated by a sudden decrease in oxygen consumption. The critical hemoglobin
      concentration quantified at this time point was the primary endpoint; secondary
      endpoints were hemodynamic and oxygen transport parameters. RESULTS: Thoracic
      epidural anesthesia elicited only a moderate decrease in mean arterial pressure
      and cardiac index and a transient decrease in oxygen extraction ratio. During
      progressive anemia, the compensatory increases in cardiac index and oxygen
      extraction ratio were not compromised by thoracic epidural anesthesia. Critical
      hemoglobin concentration was reached at identical levels in both groups
      (ropivacaine group: 2.5 +/- 0.6 g/dl, saline group: 2.5 +/- 0.6 g/dl).
      CONCLUSION: Thoracic epidural anesthesia with ropivacaine 0.2% does not decrease
      the tolerance to acute normovolemic anemia in healthy pigs. The hemodynamic
      compensation of acute anemia is fully preserved despite sympathetic block, and
      the critical hemoglobin concentration remains unaffected.

PMID- 24937076
TI  - [Physical capacity as an indicator of mortality?--Physical capacity tests help to
      predict mortality].

PMID- 24937077
TI  - [Efficacy and sustainability of a smoking prevention program for pupils-
      "ohnekippe"].
AB  - BACKGROUND: Since 2000 the Thoraxklinik Heidelberg offers the primary smoking
      prevention program "ohnekippe" for children aged 12-14 years. This program was
      scientifically evaluated to test its efficacy and sustainability. METHODS: All
      pupils participating in this prevention program (n=1427) were asked to complete a
      written survey regarding their smoking behaviour at the time of intervention
      (baseline) and after one year. A control group (n=1412) without intervention from
      comparable schools and grades were questioned in parallel. Afterwards the program
      was modified with active involvement of schools and then data regarding smoking
      prevalence of young people were compared based on the microcensus 2005 and 2009.
      RESULTS: 187 (13,4 %) pupils in the intervention and 215 (15,4 %) pupils in the
      control group were smokers at baseline. One year after, the number of regular and
      occasional smokers had increased from 11.2 % to 21.2 % in both groups without
      significant differences. Besides age and initial smoking status the "peer group"
      had important influence on smoking behaviour of young people. After modifying the
      program the number of smoking young people in the catchment area of "ohnekippe"
      has decreased significantly (7.8 %). Overall smoking prevalence in this age group
      was much lower (11,8 %) than in the rest of Baden-Wurttemberg (16.0 %) and of
      Germany (17.5 %). CONCLUSION: Smoking prevention programs for young people can be
      effective if they are appropriately designed. Not only one prevention event, but
      intensive preparation and follow-up in schools as well as involvement of the
      "peer group" is essential for a successful intervention. After appropriate
      modification the smoking prevention program "ohnekippe" shows highly promising
      success.

PMID- 24937078
TI  - [74-year-old woman with mass in the right lung hilus].

PMID- 24937079
TI  - [Tularemia in Germany].
AB  - The bacterium Francisella tularensis is known for more than 100 years by now as
      the etiological agent of the disease tularemia, a zoonotic infection with a
      worldwide distribution in the Northern Hemisphere. The prevalence of tularemia
      shows a wide geographic variation, being comparably infrequent in Germany.
      Tularemia can present itself with multiple clinical manifestations including
      ulceroglandular, glandular, oropharyngeal, oculoglandular, respiratory and
      typhoidal forms. Due to the low prevalence and the unspecific symptomatology, a
      rapid diagnosis and early start of an effective therapy are rarely obtained.
      Thus, in this article we summarize important aspects concerning etiology, ecology
      and routes of transmission, recent epidemiologic situation, clinical picture,
      diagnostics and treatment of tularemia, focusing on the situation in Germany. 

PMID- 24937080
TI  - [Dietary supplements and cardiovascular diseases].
AB  - Dietary supplements and so-called "functional foods" are advertised for primary
      and secondary prevention of cardiovascular diseases. However, there are no
      studies available that show that these products reduce "hard cardiovascular
      outcomes" such as myocardial infarction or stroke. Moreover, some studies have
      shown that dietary supplementation might do more harm than good. Therefore, prior
      to a general recommendation more data on safety and effectiveness are necessary. 

PMID- 24937081
TI  - [Development and importance of outpatient cardiac rehabilitation in German
      speaking countries].
AB  - Cardiac rehabilitation is a coordinated treatment approach. The interdisciplinary
      team aims to provide the best possible physical and psychological outcomes for
      patients with cardiac diseases. Patients should be enable to independently resume
      work and and social life. Furthermore cardiac rehabilitation wants to limit or
      reverse the progress of cardiac disease through sustained health-related life
      habits. Cardiac rehabilitation significantly contributes to long-term success
      based on comprehensive care of cardiac patients. Outpatient cardiac
      rehabilitation has shown to be effective after myocardial infarction, coronary
      artery bypass grafting and chronic heart failure. However randomized controlled
      trials were performed only in Anglo-American countries. In these trials effects
      were observed mainly for exercise-based cardiac rehabilitation programs. Because
      the results have been derived from different program settings they cannot simply
      be translated to German-speaking countries. However, several cohort studies
      predominantly performed in Germany also revealed effects of inpatient and
      outpatient cardiac rehabilitation programs for German-speaking countries. The
      most recent results demonstrated a significant reduction of recurrent events in
      patients after inpatient cardiac rehabilitation. Following the current evidence
      concerning the effect of inpatient and outpatient cardiac rehabilitation programs
      particularly after myocardial infarction international guidelines provide Class I
      (USA) and IIa (Europe) recommendation for this treatment intervention.In contrast
      to Anglo-American countries cardiac rehabilitation in Austria, Germany and
      Switzerland was established at its beginning exclusively for inpatient programs.
      In addition more and more outpatient programs were introduced in the last
      decades. Nevertheless inpatient cardiac rehabilitation is still the most common
      program in German-speaking countries.Future challenges of cardiac rehabilitation
      should not address the competition between inpatient and outpatient programs but
      provide answers to the question "which patient needs which program?" Future
      cardiac rehabilitation will offer patient-tailored programs. In German-speaking
      countries inpatient cardiac rehabilitation has long been well established whereas
      treatment potential of outpatient programs have increased. Outpatient cardiac
      rehabilitation is more flexible, close to home and it can be done part-time.
      Furhtermore, outpatient cardiac rehabilitation programs can take on important
      tasks in long-term cardiac care and thus provide relief to inpatient programs.
      The initiation of such programs is a challenge and can add to better future
      development of comprehensive cardiac rehabilitation.

PMID- 24937082
TI  - [Membranous nephropathy--crucial developments for diagnostic and treatment].

PMID- 24937083
TI  - Facile preparation of hierarchical TiO2 nano structures: growth mechanism and
      enhanced photocatalytic H2 production from water splitting using methanol as a
      sacrificial reagent.
AB  - Owing to unique features, hierarchical nanostructure of TiO2 has superior
      photocatalytic activity. In this work a facile hydrothermal route has been
      explored to prepare 3D hierarchical TiO2 (3D-HTiO2), 1D/3D hybrid hierarchical
      TiO2 composite (HHC), and 3D hierarchical protonated titanate microspheres
      H2Ti2O5.H2O (3DHPTMS) at the expense of free-standing titania nanotube membrane
      (TiO2-Memb). It proceeded through the formation of peroxotitanium complex, a
      water-soluble Ti complex as an intermediate. Mechanism of formation, role of
      membrane crystallinity, and reaction parameters giving fine control on tuning
      morphology and crystal structure have been investigated systematically.
      Photocatalytic activities were determined by measuring the amount hydrogen
      generated from water splitting under UV irradiation in the presence of methanol
      as a sacrificial reagent. Self-assembled hierarchical titania nanostructures
      exhibited much superior photocatalytic activity compared to that of starting
      material, i.e., TiO2-Memb. Enhanced photocatalytic activity is due to
      characteristic morphology, increased surface area, and enhanced production of
      photogenerated charge carriers. 

PMID- 24937084
TI  - Toward a more complete understanding of noncovalent interactions involving
      aromatic rings.
AB  - Noncovalent interactions involving aromatic rings, which include pi-stacking
      interactions, anion-pi interactions, and XH-pi interactions, among others, are
      ubiquitous in chemical and biochemical systems. Despite dramatic advances in our
      understanding of these interactions over the past decade, many aspects of these
      noncovalent interactions have only recently been uncovered, with many questions
      remaining. We summarize our computational studies aimed at understanding the
      impact of substituents and heteroatoms on these noncovalent interactions. In
      particular, we discuss our local, direct interaction model of substituent effects
      in pi-stacking interactions. In this model, substituent effects are dominated by
      electrostatic interactions of the local dipoles associated with the substituents
      and the electric field of the other ring. The implications of the local nature of
      substituent effects on pi-stacking interactions in larger systems are discussed,
      with examples given for complexes with carbon nanotubes and a small graphene
      model, as well as model stacked discotic systems. We also discuss related issues
      involving the interpretation of electrostatic potential (ESP) maps. Although ESP
      maps are widely used in discussions of noncovalent interactions, they are often
      misinterpreted. Next, we provide an alternative explanation for the origin of
      anion-pi interactions involving substituted benzenes and N-heterocycles, and show
      that these interactions are well-described by simple models based solely on
      charge-dipole interactions. Finally, we summarize our recent work on the physical
      nature of substituent effects in XH-pi interactions. Together, these results
      paint a more complete picture of noncovalent interactions involving aromatic
      rings and provide a firm conceptual foundation for the rational exploitation of
      these interactions in a myriad of chemical contexts. 

PMID- 24937085
TI  - Effect of smoking on the pharmacokinetics of inhaled loxapine.
AB  - BACKGROUND: Loxapine inhalation powder delivered by a hand-held device as a
      thermally generated aerosol (ADASUVE) was recently approved in the United States
      and European Union for use in the acute treatment of agitation in patients with
      bipolar disorder or schizophrenia. As smokers comprise a large subpopulation of
      these patients, and many antipsychotic drugs require dose adjustments for
      smokers, the objective of this study was to compare the pharmacokinetics of
      inhaled loxapine administered to smokers and nonsmokers. METHODS:
      Pharmacokinetics and sedation pharmacodynamics using a visual analog scale were
      studied in 35 male and female adult subjects (18 nonsmokers and 17 smokers)
      following a single dose of 10 mg of inhaled loxapine. Blood samples were drawn at
      predose, 30 seconds, 1, 2, 3, 10, 30, and 60 minutes, and 2, 6, 12, and 24 hours
      after dosing. Loxapine and 8-OH-loxapine were analyzed using reverse-phase liquid
      chromatography coupled with a tandem mass spectrometer. Pharmacokinetic
      parameters assessed included Cmax, Tmax, AUCinf, and T1/2 for loxapine and 8-OH
      loxapine. Geometric mean ratios (GMRs) were determined for smokers to nonsmokers.
      RESULTS: Loxapine Cmax was similar in smokers and nonsmokers with a GMR of 99.0%.
      The median loxapine Tmax was 1.88 and 1.01 minutes for nonsmokers and smokers,
      respectively. Loxapine AUCinf and AUClast values in nonsmokers were comparable
      with smokers (GMRs of 85.3% and 86.7%, respectively). A slight decrease in the
      observed mean terminal half-life values was observed for smokers (6.52 hours for
      smokers and 7.30 hours for nonsmokers). CONCLUSIONS: Sedation profiles and visual
      analog scale scores at each time point were similar for nonsmokers and smokers.
      It was concluded that inhaled loxapine does not require dosage adjustment based
      on smoking behavior.

PMID- 24937086
TI  - Large-area atomically thin MoS2 nanosheets prepared using electrochemical
      exfoliation.
AB  - Molybdenum disulfide (MoS2) is an extremely intriguing material because of its
      unique electrical and optical properties. The preparation of large-area and high
      quality MoS2 nanosheets is an important step in a wide range of applications.
      This study demonstrates that monolayer and few-layer MoS2 nanosheets can be
      obtained from electrochemical exfoliation of bulk MoS2 crystals. The lateral size
      of the exfoliated MoS2 nanosheets is in the 5-50 MUm range, which is much larger
      than that of chemically or liquid-phase exfoliated MoS2 nanosheets. The MoS2
      nanosheets undergo low levels of oxidation during electrochemical exfoliation. In
      addition, microscopic and spectroscopic characterizations indicate that the
      exfoliated MoS2 nanosheets are of high quality and have an intrinsic structure. A
      back-gate field-effect transistor was fabricated using an exfoliated monolayer
      MoS2 nanosheet. The on/off current ratio is over 10(6), and the field-effect
      mobility is approximately 1.2 cm(2) V(-1) s(-1); these values are comparable to
      the results for micromechanically exfoliated MoS2 nanosheets. The electrochemical
      exfoliation method is simple and scalable, and it can be applied to exfoliate
      other transition metal dichalcogenides. 

PMID- 24937087
TI  - Facile synthesis of enzyme-inorganic hybrid nanoflowers and its application as a
      colorimetric platform for visual detection of hydrogen peroxide and phenol.
AB  - This study reports a facile approach for the synthesis of horseradish peroxidise
      (HRP)-inorganic hybrid nanoflowers by self-assembly of HRP and copper phosphate
      (Cu3(PO4)2.3H2O) in aqueous solution. Several reaction parameters that affect the
      formation of the hybrid nanoflowers were investigated and a hierarchical
      flowerlike spherical structure with hundreds of nanopetals was obtained under the
      optimum synthetic conditions. The enzymatic activity of HRP embedded in hybrid
      naonflowers was evaluated based on the principle of HRP catalyzing the oxidation
      of o-phenylenediamine (OPD) in the presence of hydrogen peroxide (H2O2). The
      results showed that 506% enhancement of enzymatic activity in the hybrid
      nanoflowers could be achieved compared with the free HRP in solution. Taking
      advantages of the structural feature with catalytic property, a nanoflower-based
      colorimetric platform was newly designed and applied for fast and sensitive
      visual detection of H2O2 and phenol. The limits of detection (LODs) for H2O2 and
      phenol were as low as 0.5 MUM and 1.0 MUM by the naked-eye visualization, which
      meet the requirements of detection of both analytes in clinical diagnosis and
      environmental water. The proposed method has been successfully applied to the
      analysis of low-level H2O2 in spiked human serum and phenol in sewage,
      respectively. The recoveries for all the determinations were higher than 92.6%.
      In addition, the hybrid nanoflowers exhibited excellent reusability and
      reproducibility in cycle analysis. These primary results demonstrate that the
      hybrid nanoflowers have a great potential for applications in biomedical and
      environmental chemistry. 

PMID- 24937088
TI  - Solution structure of the 2A protease from a common cold agent, human rhinovirus
      C2, strain W12.
AB  - Human rhinovirus strains differ greatly in their virulence, and this has been
      correlated with the differing substrate specificity of the respective 2A protease
      (2Apro). Rhinoviruses use their 2Apro to cleave a spectrum of cellular proteins
      important to virus replication and anti-host activities. These enzymes share a
      chymotrypsin-like fold stabilized by a tetra-coordinated zinc ion. The catalytic
      triad consists of conserved Cys (C105), His (H34), and Asp (D18) residues. We
      used a semi-automated NMR protocol developed at NMRFAM to determine the solution
      structure of 2Apro (C105A variant) from an isolate of the clinically important
      rhinovirus C species (RV-C). The backbone of C2 2Apro superimposed closely (1.41
      1.81 A rmsd) with those of orthologs from RV-A2, coxsackie B4 (CB4), and
      enterovirus 71 (EV71) having sequence identities between 40% and 60%. Comparison
      of the structures suggest that the differential functional properties of C2 2Apro
      stem from its unique surface charge, high proportion of surface aromatics, and
      sequence surrounding the di-tyrosine flap. 

PMID- 24937089
TI  - Alphavirus-based vaccines.
AB  - Alphavirus vectors have demonstrated high levels of transient heterologous gene
      expression both in vitro and in vivo and, therefore, possess attractive features
      for vaccine development. The most commonly used delivery vectors are based on
      three single-stranded encapsulated alphaviruses, namely Semliki Forest virus,
      Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have
      been applied as replication-deficient recombinant viral particles and, more
      recently, as replication-proficient particles. Moreover, in vitro transcribed
      RNA, as well as layered DNA vectors have been applied for immunization. A large
      number of highly immunogenic viral structural proteins expressed from alphavirus
      vectors have elicited strong neutralizing antibody responses in multispecies
      animal models. Furthermore, immunization studies have demonstrated robust
      protection against challenges with lethal doses of virus in rodents and primates.
      Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted
      in prophylactic protection against challenges with tumor-inducing cancerous
      cells. As certain alphaviruses, such as Chikungunya virus, have been associated
      with epidemics in animals and humans, attention has also been paid to the
      development of vaccines against alphaviruses themselves. Recent progress in
      alphavirus vector development and vaccine technology has allowed conducting
      clinical trials in humans. 

PMID- 24937090
TI  - Decreased fixation stability of the preferred retinal location in juvenile
      macular degeneration.
AB  - Macular degeneration is the main cause for diminished visual acuity in the
      elderly. The juvenile form of macular degeneration has equally detrimental
      consequences on foveal vision. To compensate for loss of foveal vision most
      patients with macular degeneration adopt an eccentric preferred retinal location
      that takes over tasks normally performed by the healthy fovea. It is unclear
      however, whether the preferred retinal locus also develops properties typical for
      foveal vision. Here, we investigated whether the fixation characteristics of the
      preferred retinal locus resemble those of the healthy fovea. For this purpose, we
      used the fixation-offset paradigm and tracked eye-position using a high spatial
      and temporal resolution infrared eye-tracker. The fixation-offset paradigm
      measures release from fixation under different fixation conditions and has been
      shown useful to distinguish between foveal and non-foveal fixation. We measured
      eye-movements in nine healthy age-matched controls and five patients with
      juvenile macular degeneration. In addition, we performed a simulation with the
      same task in a group of five healthy controls. Our results show that the
      preferred retinal locus does not adopt a foveal type of fixation but instead
      drifts further away from its original fixation and has overall increased fixation
      instability. Furthermore, the fixation instability is most pronounced in low
      frequency eye-movements representing a slow drift from fixation. We argue that
      the increased fixation instability cannot be attributed to fixation under an
      unnatural angle. Instead, diminished visual acuity in the periphery causes
      reduced oculomotor control and results in increased fixation instability. 

PMID- 24937092
TI  - Surface modification of cellulose nanocrystals.
AB  - Chemical modification of cellulose nanocrystals is an increasingly popular topic
      in the literature. This review analyses the type of cellulose nanocrystal
      modification reactions that have been published in the literature thus far and
      looks at the steps that have been taken towards analysing the products of the
      nanocrystal modifications. The main categories of reactions carried out on
      cellulose nanocrystals are oxidations, esterifications, amidations, carbamations
      and etherifications. More recently nucleophilic substitutions have been used to
      introduce more complex functionality to cellulose nanocrystals. Multi-step
      modifications are also considered. This review emphasizes quantification of
      modification at the nanocrystal surface in terms of degree of substitution and
      the validity of conclusions drawn from different analysis techniques in this
      area. The mechanisms of the modification reactions are presented and considered
      with respect to the effect on the outcome of the reactions. While great strides
      have been made in the quality of analytical data published in the field of
      cellulose nanocrystal modification, there is still vast scope for improvement,
      both in data quality and the quality of analysis of data. Given the difficulty of
      surface analysis, cross-checking of results from different analysis techniques is
      fundamental for the development of reliable cellulose nanocrystal modification
      techniques. 

PMID- 24937091
TI  - Evidence for an electrostatic mechanism of force generation by the bacteriophage
      T4 DNA packaging motor.
AB  - How viral packaging motors generate enormous forces to translocate DNA into viral
      capsids remains unknown. Recent structural studies of the bacteriophage T4
      packaging motor have led to a proposed mechanism wherein the gp17 motor protein
      translocates DNA by transitioning between extended and compact states,
      orchestrated by electrostatic interactions between complimentarily charged
      residues across the interface between the N- and C-terminal subdomains. Here we
      show that site-directed alterations in these residues cause force dependent
      impairments of motor function including lower translocation velocity, lower stall
      force and higher frequency of pauses and slips. We further show that the measured
      impairments correlate with computed changes in free-energy differences between
      the two states. These findings support the proposed structural mechanism and
      further suggest an energy landscape model of motor activity that couples the free
      energy profile of motor conformational states with that of the ATP hydrolysis
      cycle. 

PMID- 24937093
TI  - Deformable image registration with local rigidity constraints for cone-beam CT
      guided spine surgery.
AB  - Image-guided spine surgery (IGSS) is associated with reduced co-morbidity and
      improved surgical outcome. However, precise localization of target anatomy and
      adjacent nerves and vessels relative to planning information (e.g., device
      trajectories) can be challenged by anatomical deformation. Rigid registration
      alone fails to account for deformation associated with changes in spine
      curvature, and conventional deformable registration fails to account for rigidity
      of the vertebrae, causing unrealistic distortions in the registered image that
      can confound high-precision surgery. We developed and evaluated a deformable
      registration method capable of preserving rigidity of bones while resolving the
      deformation of surrounding soft tissue. The method aligns preoperative CT to
      intraoperative cone-beam CT (CBCT) using free-form deformation (FFD) with
      constraints on rigid body motion imposed according to a simple intensity
      threshold of bone intensities. The constraints enforced three properties of a
      rigid transformation-namely, constraints on affinity (AC), orthogonality (OC),
      and properness (PC). The method also incorporated an injectivity constraint (IC)
      to preserve topology. Physical experiments involving phantoms, an ovine spine,
      and a human cadaver as well as digital simulations were performed to evaluate the
      sensitivity to registration parameters, preservation of rigid body morphology,
      and overall registration accuracy of constrained FFD in comparison to
      conventional unconstrained FFD (uFFD) and Demons registration. FFD with
      orthogonality and injectivity constraints (denoted FFD+OC+IC) demonstrated
      improved performance compared to uFFD and Demons. Affinity and properness
      constraints offered little or no additional improvement. The FFD+OC+IC method
      preserved rigid body morphology at near-ideal values of zero dilatation (D =
      0.05, compared to 0.39 and 0.56 for uFFD and Demons, respectively) and shear (S =
      0.08, compared to 0.36 and 0.44 for uFFD and Demons, respectively). Target
      registration error (TRE) was similarly improved for FFD+OC+IC (0.7 mm), compared
      to 1.4 and 1.8 mm for uFFD and Demons. Results were validated in human cadaver
      studies using CT and CBCT images, with FFD+OC+IC providing excellent preservation
      of rigid morphology and equivalent or improved TRE. The approach therefore
      overcomes distortions intrinsic to uFFD and could better facilitate high
      precision IGSS.

PMID- 24937095
TI  - Implication of dopamine D3 receptor activation in the reversion of Parkinson's
      disease-related motivational deficits.
AB  - In addition to the classical motor symptoms, motivational and affective deficits
      are core impairments of Parkinson's disease (PD). We recently demonstrated, by
      lesional approaches in rats, that degeneration of the substantia nigra pars
      compacta (SNc) dopaminergic (DA) neurons is likely to have a crucial role in the
      development of these neuropsychiatry symptoms. We have also shown that, as in
      clinical investigations, chronic treatment with levodopa or the DA D2/D3 receptor
      (D2/D3R) agonist ropinirole specifically reverses these PD-related motivational
      deficits. The roles of specific DA receptor subtypes in such reversal effects
      remain, however, unknown. We therefore investigated here the precise involvement
      of D1, D2 and D3R in the reversal of the motivational and affective deficits
      related to SNc DA neuronal loss. Three weeks after bilateral and partial 6
      hydroxydopamine (6-OHDA) SNc lesions, rats received 14 daily intraperitoneal
      administrations of the selective D1R agonist SKF-38393 (2.5 or 3.5 mg kg(-1)),
      the selective D2R agonist sumanirole (0.1 or 0.15 mg kg(-1)), or the preferring
      D3R gonist PD-128907 (0.1 or 0.15 mg kg(-1)). Anxiety-, depressive-like and
      motivated behaviors were assessed in an elevated-plus maze, a forced-swim test,
      and an operant sucrose self-administration procedure, respectively. All DA
      agonists attenuated anxiety- and depressive-like behaviors. However, only PD
      128907 reversed the motivational deficits induced by 6-OHDA SNc lesions. This
      effect was blocked by a selective D3R (SB-277011A, 10 mg kg(-1)), but not D2R (L
      741,626, 1.5 mg kg(-1)), antagonist. These data provide strong evidence for the
      role of D3R in motivational processes and identify this receptor as a potentially
      valuable target for the treatment of PD-related neuropsychiatric symptoms.

PMID- 24937094
TI  - Reversal of autism-like behaviors and metabolism in adult mice with single-dose
      antipurinergic therapy.
AB  - Autism spectrum disorders (ASDs) now affect 1-2% of the children born in the
      United States. Hundreds of genetic, metabolic and environmental factors are known
      to increase the risk of ASD. Similar factors are known to influence the risk of
      schizophrenia and bipolar disorder; however, a unifying mechanistic explanation
      has remained elusive. Here we used the maternal immune activation (MIA) mouse
      model of neurodevelopmental and neuropsychiatric disorders to study the effects
      of a single dose of the antipurinergic drug suramin on the behavior and
      metabolism of adult animals. We found that disturbances in social behavior,
      novelty preference and metabolism are not permanent but are treatable with
      antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single
      dose of suramin (20 mg kg(-1) intraperitoneally (i.p.)) given to 6-month-old
      adults restored normal social behavior, novelty preference and metabolism.
      Comprehensive metabolomic analysis identified purine metabolism as the key
      regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic
      pathways that were disturbed in the MIA model. Two days after treatment, the
      suramin concentration in the plasma and brainstem was 7.64 MUM pmol MUl(-1) (+/
      0.50) and 5.15 pmol mg(-1) (+/-0.49), respectively. These data show good uptake
      of suramin into the central nervous system at the level of the brainstem. Most of
      the improvements associated with APT were lost after 5 weeks of drug washout,
      consistent with the 1-week plasma half-life of suramin in mice. Our results show
      that purine metabolism is a master regulator of behavior and metabolism in the
      MIA model, and that single-dose APT with suramin acutely reverses these
      abnormalities, even in adults.

PMID- 24937097
TI  - Hemostatic agents for bleeding: recombinant-activated factor VII and beyond.
AB  - A rapid restoration of hemostasis should be regarded as a primary goal for
      management of critical bleeding, which often represents a life-threatening
      condition. Among the various therapeutic strategies available in this clinical
      setting, we aim to summarize in this narrative review the current status on the
      use of recombinant-activated factor VII and prothrombin complex concentrates. The
      safety and effectiveness of these hemostatic agents in reversal of the
      anticoagulant effects of vitamin K antagonists will be also explored. In
      addition, their role in the management of acute bleeding associated with the
      newer direct oral anticoagulants dabigatran, rivaroxaban, and apixaban will be
      analyzed in a dedicated section. 

PMID- 24937096
TI  - Effects of genetic and early environmental risk factors for depression on
      serotonin transporter expression and methylation profiles.
AB  - The serotonin transporter (SERT) gene-linked polymorphic region (5-HTTLPR) has
      been implicated in moderating the link between life stress and depression.
      However, respective molecular pathways of gene-environment (GxE) interaction are
      largely unknown. Sustained alterations in SERT gene expression profiles, possibly
      mediated by epigenetic modifications, are a frequent correlate of depression and
      may thus constitute a putative mediator of GxE interaction. Here, we aimed to
      investigate joint effects of 5-HTTLPR and self-reported environmental adversity
      throughout the lifespan (prenatal, early and recent stress/trauma) on in vivo
      SERT mRNA expression in peripheral blood cells. To further evaluate whether
      environmentally induced changes in SERT expression are mediated by epigenetic
      modifications, we analyzed 83 CpG sites within a 799-bp promoter-associated CpG
      island of the SERT gene using the highly sensitive method of bisulfite
      pyrosequencing. Participants were 133 healthy young adults. Our findings show
      that both the 5-HTTLPR S allele and maternal prenatal stress/child maltreatment
      are associated with reduced in vivo SERT mRNA expression in an additive manner.
      Remarkably, individuals carrying both the genetic and the environmental risk
      factors exhibited 32.8% (prenatal stress) and 56.3% (child maltreatment) lower
      SERT mRNA levels compared with those without any risk factor. Our data further
      indicated that changes in SERT mRNA levels were unlikely to be mediated by DNA
      methylation profiles within the SERT CpG island. It is thus conceivable that the
      persistent changes in SERT expression may in turn relate to altered serotonergic
      functioning and possibly convey differential disease vulnerability associated
      with 5-HTTLPR and early adversity. 

PMID- 24937098
TI  - Neonatal sepsis is mediated by maternal fever in labour epidural analgesia.
AB  - Women delivering with EA (EA group) were matched on parity with 453 women with
      deliveries without EA (non-EA group). Significantly more neonates born in the EA
      group had fever >= 38.0 degrees C (11.6% vs 1.8%, p < 0.001) at birth. The
      overall incidence of neonatal sepsis, based on clinical symptoms and defined as
      proven (by a positive blood culture) or suspected (no positive blood culture),
      was significantly higher in the EA group (6.0% vs 2.2%; p = 0.002), but the
      incidence of proven neonatal sepsis alone was not (0.4% vs 0%; p = 0.250). EA
      turned out to be an independent risk factor for neonatal sepsis (adjusted OR
      2.43, 95% CI 1.15-5.13; p = 0.020). However, in the EA group as well as the non
      EA group, the incidence of neonatal sepsis was significantly higher in mothers
      with intrapartum fever compared with afebrile mothers (11.0% vs 2.9% in the EA
      group; p = 0.004; 8.2% vs 1.3% in the non-EA group; p = 0.006). Therefore we
      conclude, that the positive association between neonatal sepsis and labour EA is
      possibly mediated by maternal intrapartum fever.

PMID- 24937099
TI  - Bronchodilators for bronchiolitis.
AB  - BACKGROUND: Bronchiolitis is an acute, viral lower respiratory tract infection
      affecting infants and is sometimes treated with bronchodilators. OBJECTIVES: To
      assess the effects of bronchodilators on clinical outcomes in infants (0 to 12
      months) with acute bronchiolitis. SEARCH METHODS: We searched CENTRAL 2013, Issue
      12, MEDLINE (1966 to January Week 2, 2014) and EMBASE (1998 to January 2014).
      SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing bronchodilators
      (other than epinephrine) with placebo for bronchiolitis. DATA COLLECTION AND
      ANALYSIS: Two authors assessed trial quality and extracted data. We obtained
      unpublished data from trial authors. MAIN RESULTS: We included 30 trials (35 data
      sets) representing 1992 infants with bronchiolitis. In 11 inpatient and 10
      outpatient studies, oxygen saturation did not improve with bronchodilators (mean
      difference (MD) -0.43, 95% confidence interval (CI) -0.92 to 0.06, n = 1242).
      Outpatient bronchodilator treatment did not reduce the rate of hospitalization
      (11.9% in bronchodilator group versus 15.9% in placebo group, odds ratio (OR)
      0.75, 95% CI 0.46 to 1.21, n = 710). Inpatient bronchodilator treatment did not
      reduce the duration of hospitalization (MD 0.06, 95% CI -0.27 to 0.39, n =
      349).Effect estimates for inpatients (MD -0.62, 95% CI -1.40 to 0.16) were
      slightly larger than for outpatients (MD -0.25, 95% CI -0.61 to 0.11) for
      oximetry. Oximetry outcomes showed significant heterogeneity (I(2) statistic =
      81%). Including only studies with low risk of bias had little impact on the
      overall effect size of oximetry (MD -0.38, 95% CI -0.75 to 0.00) but results were
      close to statistical significance.In eight inpatient studies, there was no change
      in average clinical score (standardized MD (SMD) -0.14, 95% CI -0.41 to 0.12)
      with bronchodilators. In nine outpatient studies, the average clinical score
      decreased slightly with bronchodilators (SMD -0.42, 95% CI -0.79 to -0.06), a
      statistically significant finding of questionable clinical importance. The
      clinical score outcome showed significant heterogeneity (I(2) statistic = 73%).
      Including only studies with low risk of bias reduced the heterogeneity but had
      little impact on the overall effect size of average clinical score (SMD -0.22,
      95% CI -0.41 to -0.03).Sub-analyses limited to nebulized albuterol or salbutamol
      among outpatients (nine studies) showed no effect on oxygen saturation (MD -0.19,
      95% CI -0.59 to 0.21, n = 572), average clinical score (SMD -0.36, 95% CI -0.83
      to 0.11, n = 532) or hospital admission after treatment (OR 0.77, 95% CI 0.44 to
      1.33, n = 404).Adverse effects included tachycardia, oxygen desaturation and
      tremors. AUTHORS' CONCLUSIONS: Bronchodilators such as albuterol or salbutamol do
      not improve oxygen saturation, do not reduce hospital admission after outpatient
      treatment, do not shorten the duration of hospitalization and do not reduce the
      time to resolution of illness at home. Given the adverse side effects and the
      expense associated with these treatments, bronchodilators are not effective in
      the routine management of bronchiolitis. This meta-analysis continues to be
      limited by the small sample sizes and the lack of standardized study design and
      validated outcomes across the studies. Future trials with large sample sizes,
      standardized methodology across clinical sites and consistent assessment methods
      are needed to answer completely the question of efficacy.

PMID- 24937100
TI  - Excimer laser refractive surgery versus phakic intraocular lenses for the
      correction of moderate to high myopia.
AB  - BACKGROUND: Myopia is a condition in which the focusing power (refraction) of the
      eye is greater than that required for clear distance vision. There are two main
      types of surgical correction for moderate to high myopia; excimer laser and
      phakic intraocular lenses (IOLs). Excimer laser refractive surgery for myopia
      works by removing corneal stroma to lessen the refractive power of the cornea and
      to bring the image of a viewed object into focus onto the retina rather than in
      front of it. Phakic IOLs for the treatment of myopia work by diverging light rays
      so that the image of a viewed object is brought into focus onto the retina rather
      than in front of the retina. They can be placed either in the anterior chamber of
      the eye in front of the iris or in the posterior chamber of the eye between the
      iris and the natural lens. OBJECTIVES: To compare excimer laser refractive
      surgery and phakic IOLs for the correction of moderate to high myopia by
      evaluating postoperative uncorrected visual acuity, refractive outcome, potential
      loss of best spectacle corrected visual acuity (BSCVA) and the incidence of
      adverse outcomes. SEARCH METHODS: We searched CENTRAL (which contains the
      Cochrane Eyes and Vision Group Trials Register) (2014, Issue 1), Ovid MEDLINE,
      Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid
      OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February
      2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization
      (WHO) International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 11 February 2014. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs) comparing excimer laser refractive surgery and phakic IOLs for the
      correction of myopia greater than 6.0 diopters (D) spherical equivalent. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and
      extracted data. We performed data analysis. We summarised data for outcomes using
      odds ratios. We used a fixed-effect model as only three trials were included in
      the review. MAIN RESULTS: This review included three RCTs with a total of 228
      eyes. The range of myopia of included patients was -6.0 D to -20.0 D of myopia
      with up to 4.0 D of myopic astigmatism. The percentage of eyes with uncorrected
      visual acuity (UCVA) of 20/20 or better at 12 months postoperative was not
      significantly different between the two groups. Phakic IOL surgery was safer than
      excimer laser surgical correction for moderate to high myopia as it results in
      significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12
      months postoperatively. However there is a low risk of developing early cataract
      with phakic IOLs. Phakic IOL surgery appears to result in better contrast
      sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL
      surgery also scored more highly on patient satisfaction/preference
      questionnaires. AUTHORS' CONCLUSIONS: The results of this review suggest that, at
      one year post surgery, phakic IOLs are safer than excimer laser surgical
      correction for moderate to high myopia in the range of -6.0 to -20.0 D and phakic
      IOLs are preferred by patients. While phakic IOLs might be accepted clinical
      practice for higher levels of myopia (greater than or equal to 7.0 D of myopic
      spherical equivalent with or without astigmatism), it may be worth considering
      phakic IOL treatment over excimer laser correction for more moderate levels of
      myopia (less than or equal to 7.0 D of myopic spherical equivalent with or
      without astigmatism). Further RCTs adequately powered for subgroup analysis are
      necessary to further elucidate the ideal range of myopia for phakic IOLs. This
      data should be considered alongside comparative data addressing long-term safety
      as it emerges.

PMID- 24937101
TI  - Nutrition, illness, and injury in aquatic sports.
AB  - In this review, we outline key principles for prevention of injury and illness in
      aquatic sports, detail the epidemiology of injury and illness in aquatic athletes
      at major international competitions and in training, and examine the relevant
      scientific evidence on nutrients for reducing the risk of illness and injury.
      Aquatic athletes are encouraged to consume a well-planned diet with sufficient
      calories, macronutrients (particularly carbohydrate and protein), and
      micronutrients (particularly iron, zinc, and vitamins A, D, E, B6, and B12) to
      maintain health and performance. Ingesting carbohydrate via sports drinks, gels,
      or sports foods during prolonged training sessions is beneficial in maintaining
      energy availability. Studies of foods or supplements containing plant polyphenols
      and selected strains of probiotic species are promising, but further research is
      required. In terms of injury, intake of vitamin D, protein, and total caloric
      intake, in combination with treatment and resistance training, promotes recovery
      back to full health and training. 

PMID- 24937103
TI  - Missing lead and high 3He/4He in ancient sulfides associated with continental
      crust formation.
AB  - Major terrestrial reservoirs have Pb isotopes more radiogenic than the bulk
      silicate Earth. This requires a missing unradiogenic Pb reservoir, which has been
      argued to reside in the lower continental crust or dissolved in the core.
      Chalcophile element studies indicate that continent formation requires the
      formation of sulfide-bearing mafic cumulates in arcs. Because Pb, but not U,
      partitions into sulfides, we show that continent formation must have
      simultaneously generated time-integrated unradiogenic Pb reservoirs composed of
      sulfide-bearing cumulates, now recycled back into the mantle or stored deep in
      the continental lithosphere. The generation of such cumulates could also lead to
      coupled He-Pb isotopic systematics because (4)He is also produced during U-Th-Pb
      decay. Here, we show that He may be soluble in sulfide melts, such that sulfide
      bearing cumulates would be enriched in both Pb and He relative to U and Th,
      "freezing" in He and Pb isotopes of the ambient mantle at the time of sulfide
      formation. This implies that ancient sulfide-bearing cumulates would be
      characterized by unradiogenic Pb and He isotopes (high-(3)He/(4)He). These
      primitive signatures are usually attributed to primordial, undifferentiated
      mantle, but in this case, they are the very imprint of mantle differentiation via
      continent formation. 

PMID- 24937104
TI  - GPR103 antagonists demonstrating anorexigenic activity in vivo: design and
      development of pyrrolo[2,3-c]pyridines that mimic the C-terminal Arg-Phe motif of
      QRFP26.
AB  - GPR103, a G-protein coupled receptor, has been reported to have orexigenic
      properties through activation by the endogenous neuropeptide ligands QRFP26 and
      QRFP43. Recognizing that central administration of QRFP26 and QRFP43 increases
      high fat food intake in rats, we decided to investigate if antagonists of GPR103
      could play a role in managing feeding behaviors. Here we present the development
      of a new series of pyrrolo[2,3-c]pyridines as GPR103 small molecule antagonists
      with GPR103 affinity, drug metabolism and pharmacokinetics and safety parameters
      suitable for drug development. In a preclinical obesity model measuring food
      intake, the anorexigenic effect of a pyrrolo[2,3-c]pyridine GPR103 antagonist was
      demonstrated. In addition, the dynamic 3D solution structure of the C-terminal
      heptapeptide of the endogenous agonist QRFP26(20-26) was determined using NMR.
      The synthetic pyrrolo[2,3-c]pyridine antagonists were compared to this
      experimental structure, which displayed a possible overlay of pharmacophore
      features supportive for further design of GPR103 antagonists. 

PMID- 24937102
TI  - Alterations in energy/redox metabolism induced by mitochondrial and environmental
      toxins: a specific role for glucose-6-phosphate-dehydrogenase and the pentose
      phosphate pathway in paraquat toxicity.
AB  - Parkinson's disease (PD) is a multifactorial disorder with a complex etiology
      including genetic risk factors, environmental exposures, and aging. While energy
      failure and oxidative stress have largely been associated with the loss of
      dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental
      toxins, very little is known regarding the alterations in energy metabolism
      associated with mitochondrial dysfunction and their causative role in cell death
      progression. In this study, we investigated the alterations in the energy/redox
      metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins
      (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6
      OHDA]) in order to identify common and/or different mechanisms of toxicity. A
      combined metabolomics approach using nuclear magnetic resonance (NMR) and direct
      infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to
      identify unique metabolic profile changes in response to these neurotoxins.
      Paraquat exposure induced the most profound alterations in the pentose phosphate
      pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP
      metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5
      lactone, and erythrose-4-phosphate were increased by paraquat treatment, which
      was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis
      also found an increase in the expression of glucose-6-phosphate dehydrogenase
      (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine
      dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively
      increased paraquat toxicity, while its inhibition with 6-aminonicotinamide
      inhibited paraquat-induced oxidative stress and cell death. These results suggest
      that paraquat "hijacks" the PPP to increase NADPH reducing equivalents and
      stimulate paraquat redox cycling, oxidative stress, and cell death. Our study
      clearly demonstrates that alterations in energy metabolism, which are specific
      for distinct mitochondiral/environmental toxins, are not bystanders to energy
      failure but also contribute significant to cell death progression.

PMID- 24937106
TI  - Molecular and electronic structure of dinuclear uranium bis-MU-oxo complexes with
      diamond core structural motifs.
AB  - In a multiple-bond metathesis reaction, the triazacyclononane (tacn)-anchored
      methyl- and neopentyl (nP)-substituted tris(aryloxide) U(III) complex
      [(((nP,Me)ArO)3tacn)U(III)] (1) reacts with mesityl azide and CO2 to form mesityl
      isocyanate and the dinuclear bis(MU-oxo)-bridged U(V)/U(V) complex
      [{(((nP,Me)ArO)3tacn)U(V)}2(MU-O)2] (3). This reaction proceeds via the
      mononuclear U(V) imido intermediate [(((nP,Me)ArO)3tacn)U(V)(NMes)] (2), which
      has been synthesized and fully characterized independently. The dimeric U(V) oxo
      species shows rich redox behavior: complex 3 can be reduced by one and two
      electrons, respectively, yielding the mixed-valent U(IV)/U(V) bis(MU-oxo) complex
      [K(crypt)][{(((nP,Me)ArO)3tacn)U(IV/V)}2(MU-O)2] (7) and the U(IV)/U(IV) bis(MU
      oxo) complex K2[{(((nP,Me)ArO)3tacn)U(IV)}2(MU-O)2] (6). In addition, complex 3
      can be oxidized to provide the mononuclear uranium(VI) oxo complexes
      [(((nP,Me)ArO)3tacn)U(VI)(O)eq(OTf)ax] (8) and
      [(((nP,Me)ArO)3tacn)U(VI)(O)eq]SbF6 (9). The unique series of bis(MU-oxo)
      complexes also shows notable magnetic behavior, which was investigated in detail
      by UV/vis/NIR and EPR spectroscopy as well as SQUID magnetization studies. In
      order to understand possible magnetic exchange phenomena, the mononuclear
      terminal oxo complexes [(((nP,Me)ArO)3tacn)U(V)(O)(O-pyridine)] (4) and
      [(((nP,Me)ArO)3tacn)U(V)(O)(O-NMe3)] (5) were synthesized and fully
      characterized. The magnetic study revealed an unusually strong antiferromagnetic
      exchange coupling between the two U(V) ions in 3. Examination of the (18)O
      labeled bis(MU-oxo)-bridged dinuclear complexes 3, 6, and 7 allowed for the first
      time the unambiguous assignment of the vibrational signature of the [U(MU-O)2U]
      diamond core structural motif. 

PMID- 24937110
TI  - Editorial.

PMID- 24937108
TI  - In vivo tumor vasculature targeted PET/NIRF imaging with TRC105(Fab)-conjugated,
      dual-labeled mesoporous silica nanoparticles.
AB  - Multifunctional mesoporous silica nanoparticles (MSN) with well-integrated
      multimodality imaging properties have generated increasing research interest in
      the past decade. However, limited progress has been made in developing MSN-based
      multimodality imaging agents to image tumors. We describe the successful
      conjugation of, copper-64 ((64)Cu, t1/2 = 12.7 h), 800CW (a near-infrared
      fluorescence [NIRF] dye), and TRC105 (a human/murine chimeric IgG1 monoclonal
      antibody) to the surface of MSN via well-developed surface engineering
      procedures, resulting in a dual-labeled MSN for in vivo targeted positron
      emission tomography (PET) imaging/NIRF imaging of the tumor vasculature.
      Pharmacokinetics and tumor targeting efficacy/specificity in 4T1 murine breast
      tumor-bearing mice were thoroughly investigated through various in vitro, in
      vivo, and ex vivo experiments. Dual-labeled MSN is an attractive candidate for
      future cancer theranostics. 

PMID- 24937109
TI  - Advances to improve the eating and cooking qualities of rice by marker-assisted
      breeding.
AB  - The eating and cooking qualities of rice are heavily emphasized in breeding
      programs because they determine market values and they are the appealing
      attributes sought by consumers. Conventional breeding has developed traditional
      varieties with improved eating and cooking qualities. Recently, intensive genetic
      studies have pinpointed the genes that control eating and cooking quality traits.
      Advances in genetic studies have developed molecular techniques, thereby allowing
      marker-assisted breeding (MAB) for improved eating and cooking qualities in rice.
      MAB has gained the attention of rice breeders for the advantages it can offer
      that conventional breeding cannot. There have been successful cases of using MAB
      to improve the eating and cooking qualities in rice over the years. Nevertheless,
      MAB should be applied cautiously given the intensive effort needed for
      genotyping. Perspectives from conventional breeding to marker-assisted breeding
      will be discussed in this review for the advancement of the eating and cooking
      qualities of fragrance, amylose content (AC), gel consistency (GC) and
      gelatinization temperature (GT) in rice. These four parameters are associated
      with eating and cooking qualities in rice. The genetic basis of these four
      parameters is also included in this review. MAB is another approach to rice
      variety improvement and development in addition to being an alternative to
      genetic engineering. The MAB approach shortens the varietal development time, and
      is therefore able to deliver improved rice varieties to farmers within a shorter
      period of time. 

PMID- 24937111
TI  - Efficacy and safety of long-term risperidone treatment.
AB  - INTRODUCTION: While efficacy in treatment of the acute phase of schizophrenia is
      well established for so-called atypical antipsychotics, more data regarding long
      term treatment are needed. METHOD: In a naturalistic, open-label study, 32
      patients were included in order to investigate the efficacy and safety of
      risperidone over 3 years of treatment; 26 of them were treatment-resistant to the
      previously used antipsychotic drugs (except clozapine). RESULTS: At the end of
      the first year, 20 of these 26 patients showed at least partial improvement. At
      the end of the third year, 17 patients were still being treated with risperidone.
      While eight patients were lost to follow-up, six relapsed in spite of good
      compliance. All the adverse events which occurred during treatment were strictly
      dose-dependent and disappeared when the dose was lowered to 4 mg daily.
      CONCLUSIONS: Within the limits of naturalistic studies, it can be concluded that
      risperidone seemed to be an effective and safe drug for long-term treatment in
      the majority of our patients. (Int J Psych Clin Pract 2002; 6: 193-197 ).

PMID- 24937107
TI  - Brain proteomics of Anopheles gambiae.
AB  - Anopheles gambiae has a well-adapted system for host localization, feeding, and
      mating behavior, which are all governed by neuronal processes in the brain.
      However, there are no published reports characterizing the brain proteome to
      elucidate neuronal signaling mechanisms in the vector. To this end, a large-scale
      mapping of the brain proteome of An. gambiae was carried out using high
      resolution tandem mass spectrometry, revealing a repertoire of >1800 proteins, of
      which 15% could not be assigned any function. A large proportion of the
      identified proteins were predicted to be involved in diverse biological processes
      including metabolism, transport, protein synthesis, and olfaction. This study
      also led to the identification of 10 GPCR classes of proteins, which could govern
      sensory pathways in mosquitoes. Proteins involved in metabolic and neural
      processes, chromatin modeling, and synaptic vesicle transport associated with
      neuronal transmission were predominantly expressed in the brain. Proteogenomic
      analysis expanded our findings with the identification of 15 novel genes and 71
      cases of gene refinements, a subset of which were validated by RT-PCR and
      sequencing. Overall, our study offers valuable insights into the brain physiology
      of the vector that could possibly open avenues for intervention strategies for
      malaria in the future.

PMID- 24937112
TI  - The long-term follow-up of women treated for postnatal depression at a specialist
      day hospital compared to routine primary care.
AB  - BACKGROUND: Postnatal depression affects approximately 13% of childbearing women.
      There are very few specialist treatment centres, despite emerging evidence that
      these units are superior to routine primary care in the short term. We
      investigated the long-term benefits of treatment for postnatal depression at a
      specialist day unit, compared to routine primary care. METHODS: Women who took
      part in an earlier study of postnatal depression were invited to participate in
      this follow-up. Self-report questionnaires (the Work, Leisure and Family Life
      Questionnaire - Modified (WLFQ-M) and the Dyadic Adjustment Scale (DAS)) were
      administered, together with the revised Clinical Interview Schedule (CIS-R).
      Information was also obtained regarding subsequent children and depressive
      episodes since the initial study. RESULTS: Of the original cohort of 60 women, 23
      agreed to participate in the follow-up. There were no significant differences
      between DAS and WLFLQ-M scores or ICD-10 diagnoses of depressive episode between
      the women who had previously received specialist care. However, the numbers were
      small and make conclusions difficult. Qualitative analysis suggests that
      treatment at a specialist unit is beneficial in the long term. CONCLUSION:
      Further, larger studies of the long-term benefits of specialist treatment need to
      be carried out. (Int J Psych Clin Pract 2002; 6: 199-203 ).

PMID- 24937113
TI  - Psychological distress of family members with cancer patients in Japan.
AB  - BACKGROUND: There were no previous studies in Japan on the psychological distress
      of members of families with cancer patients which focussed on the disclosure of
      the diagnosis of cancer. This study was designed to investigate factors that may
      have an effect on the psychological distress of family members. METHODS: The
      subjects were 95 members of families of cancer patients in the surgical ward; one
      member was recruited from each patient's family. The psychiatrist investigated
      the demographic factors of both the patient and the family member: for the
      patient - gender, age, occupation, cancer site, disclosure (or not) of cancer
      diagnosis, cancer stage and performance status (PS); for the family member -
      gender, age, occupation, relationship to the patient, physical illness, frequency
      of visiting the ward, the period from when the family member was informed of the
      diagnosis, and any past experience of the loss of close relatives due to cancer.
      Furthermore, we conducted a survey on the family member's anxiety and depression
      by using the Spielberger State - Trait Anxiety Inventory (STAI) and the Center
      for Epidemiological Studies Depression Scale (CES-D). RESULTS: A multiple
      regression analysis indicated that the factors which were associated with the
      STAI scores independently were the lack of disclosure of the diagnosis to the
      patient (P=0.01), and advanced or recurrent cancer (P=0.01). The factors which
      were associated with the CES-D scores independently were the lack of disclosure
      of the diagnosis to the patient (P=0.03), advanced or recurrent cancer (P=0.01),
      and the family member's past history of psychiatric disorders (P=0.01).
      CONCLUSIONS: The results suggested that the psychological distress of a family
      member increases when the patient is not informed of the cancer diagnosis, when
      the cancer is advanced or recurrent, and when the family member has a past
      history of psychiatric disorders. (Int J Psych Clin Pract 2002; 6: 205-210 ).

PMID- 24937114
TI  - Eight-year follow-up of olanzapine therapy in a previous treatment-refractory
      schizophrenic patient: a case report.
AB  - The introduction of atypical antipsychotic drugs during the 1990s represented a
      great step forward in the treatment of schizophrenia and other psychoses. These
      drugs might more effectively prevent relapse because of their effectiveness
      against a wider range of schizophrenic symptoms, as well as their improved
      tolerability, which leads to improved medication compliance. Olanzapine, a
      thienobenzodiazapine, is an antipsychotic drug with high affinity for the
      serotonergic receptors 5-HT 2 and 5-HT 6 and high affinity for dopaminergic
      receptors, mainly D2, D3 and D4, and with a lower propensity to cause
      extrapyramidal symptoms or increasing prolactin levels. The long-term efficacy
      and safety of olanzapine for treating treatment-refractory schizophrenia is still
      being investigated. The authors present a case of a 43-year-old man suffering
      from chronic treatment-resistant schizophrenia with both positive and negative
      symptoms, who was successfully treated with olanzapine for 8 years. (Int J Psych
      Clin Pract 2002; 6: 211-214 ). 

PMID- 24937115
TI  - A case of myclonus, resembling epileptic seizure, induced by short-term sulpiride
      treatment.
AB  - An 86-year-old woman with delusional disorder was treated with oral sulpiride at
      a dose of 200 mg/day. On the seventh day of treatment, she suddenly developed
      abrupt brief rhythmical contractions every 5 s in her neck muscles, orofacial
      muscles, muscles of upper limbs and lower legs bilaterally. Although there was no
      impairment of consciousness, her speech was interrupted by the myoclonic
      episodes. We suspected that the epileptic seizure-like myoclonus might be a drug
      induced acute extrapyramidal symptom. We therefore injected 5 mg of biperiden
      (i.m.), and the myoclonus ceased shortly thereafter. This myoclonus, resembling
      an epileptic seizure, did not recur subsequently after sulpiride treatment was
      discontinued. The present case shows that myoclonus can occur after even brief
      sulpiride treatment in certain elderly patients. (Int J Psych Clin Pract 2002; 6:
      215-216 ). 

PMID- 24937116
TI  - A zolpidem and cocaine abuse case report.
AB  - A case is presented of a 30-year-old man, prescribed zolpidem for insomnia
      arising from cocaine abuse, who sought to use this hypnotic to reduce his craving
      for cocaine. However, after taking cocaine and up to 300 mg/day zolpidem, he
      became euphoric and hyperactive. It is suggested that at high doses, zolpidem,
      like cocaine, has a stimulatory effect on the brain dopaminergic reward pathway.
      (Int J Psych Clin Pract 2002; 6: 217-219 ). 

PMID- 24937118
TI  - Abstracts from the 3rd international forum on mood and anxiety disorders,
      november 27-30, 2002, monte-carlo.

PMID- 24937120
TI  - Palladium-catalyzed alpha-arylation of sultams with aryl and heteroaryl iodides.
AB  - Palladium(0)-catalyzed conditions for the alpha-arylation of sultams with aryl
      and heteroaryl iodides have been developed. Arylation of 3-substituted 1,3
      propanesultams gave rise to high yields and high diastereomeric ratios, leading
      to the thermodynamically favored cis product. The arylation was broadly
      applicable to various electron-rich and electron-poor (hetero)aromatic iodides. 

PMID- 24937121
TI  - Association of low muscle mass and combined low muscle mass and visceral obesity
      with low cardiorespiratory fitness.
AB  - OBJECTIVE: Previous studies have shown that low cardiorespiratory fitness (CRF),
      visceral obesity and low muscle mass may share pathophysiological mechanisms,
      such as insulin resistance and chronic inflammation. In this study, we
      investigated whether low CRF is associated with low muscle mass, visceral
      obesity, and visceral obesity combined with low muscle mass. RESEARCH DESIGN AND
      METHODS: The associations between CRF and low muscle mass and combined low muscle
      mass and visceral obesity were examined in 298 apparently healthy adults aged 20
      70 years. Low muscle mass was defined using a skeletal muscle mass index (SMI)
      that was calculated using dual energy X-ray absorptiometry. Visceral obesity was
      defined as a visceral fat area (VFA) exceeding 100 cm2 in women and 130 cm2 in
      men. We classified the participants into 4 low muscle mass/visceral obesity
      groups according to SMI and VFA. CRF was measured using a cycle ergometer test.
      RESULTS: CRF level correlated positively with SMI and negatively with VFA.
      Individuals with low muscle mass had lower CRF values than those without low
      muscle mass. After adjustment for age, sex, lifestyle factors, and markers for
      insulin resistance and inflammation, participants in the lowest quartile of CRF
      had an odds ratio (OR) for low muscle mass of 4.98 compared with those in the
      highest quartile (95% confidence interval (CI) = 1.19-12.99; P for trend = 0.001)
      and an OR for combined low muscle mass and visceral obesity of 31.46 (95% CI =
      4.31-229.68; P for trend = 0.001). CONCLUSIONS: Individuals with lower CRF
      exhibited increased risk of low muscle mass and combined low muscle mass and
      visceral obesity. These results suggest that low CRF may be a potential indicator
      for low muscle mass and combined low muscle mass and visceral obesity in Korean
      adults.

PMID- 24937122
TI  - Changes in the diagnosis and treatment of patients with low grade lymphoma in
      Germany: years 2006-2009.
AB  - Today's treatment options for indolent lymphoma and chronic lymphocytic leukemia
      (CLL) range from watch & wait, immunochemotherapy up to allogeneic
      transplantation. We describe changes in the diagnosis and treatment of indolent
      lymphoma and CLL in Germany between 2006 and 2009. Two nation-wide surveys in the
      fourth quarter of 2006 and 2009 included patients with indolent lymphoma and CLL.
      Data from 576 patients from 46 centers in Q4/2006 were compared with data from
      521 patients from 57 centers in Q4/2009. The subpopulation of patients >= 70
      years of age and the number of patients with comorbidities increased from 39% to
      55% and 47% to 55%, respectively. Both in indolent lymphoma and CLL, Rituximab
      and R-based immunochemotherapy (50.6% vs. 64.4%) as well as bendamustine (4.8 %
      vs. 24%) were much more frequently applied. In contrast, high dose chemotherapy
      consolidation was almost abandoned in first line treatment. Supportive care is
      given more frequently, with exception of erythropoietin and immunoglobulins. Our
      national survey confirmed that scientific results were rapidly transferred into
      clinical care of indolent lymphoma. 

PMID- 24937124
TI  - Effect of prey limitation on competitive interactions between a native lady
      beetle, Coccinella novemnotata, and an invasive lady beetle, Coccinella
      septempunctata (Coleoptera: Coccinellidae).
AB  - The size and geographic distribution of Coccinella novemnotata Herbst populations
      have been decreasing rapidly across North America closely following the
      establishment, spread, and population growth of the invasive seven-spotted lady
      beetle, Coccinella septempunctata L. To determine whether intraguild predation
      and competition for prey may be partially responsible for the decline, we paired
      first-instar larvae of two populations of C. novemnotata (eastern and western)
      with first-instar C. septempunctata at low or high aphid densities. Survival of
      both C. novemnotata populations was significantly lower when larvae were paired
      with C. septempunctata, and western C. novemnotata exhibited significantly lower
      survival compared with the eastern population. This relationship depended on
      aphid density with the greatest survival of both C. novemnotata populations
      occurring at the high aphid density. Both male and female C. novemnotata weighed
      less on the day of eclosion when paired with C. septempunctata as compared with
      pairings with conspecifics. In a second test, C. septempunctata and C.
      novemnotata instars were varied at the start of the trial and C. novemnotata
      survival to adulthood in the presence of C. septempunctata was dependent of the
      instar of C. novemnotata used to initiate the experiment. C. novemnotata
      exhibited higher rates of survival and weighed significantly more on the day of
      eclosion when C. novemnotata was older than its C. septempunctata partner. These
      results suggest that interspecific competition including intraguild predation by
      C. septempunctata may contribute to C. novemnotata population declines, but that
      the intensity of this impact may vary across C. novemnotata populations. 

PMID- 24937123
TI  - Screening for streptomycin resistance-conferring mutations in Mycobacterium
      tuberculosis clinical isolates from Poland.
AB  - Currently, mutations in three genes, namely rrs, rpsL, and gidB, encoding 16S
      rRNA, ribosomal protein S12, and 16S rRNA-specific methyltransferase,
      respectively, are considered to be involved in conferring resistance to
      streptomycin (STR) in Mycobacterium tuberculosis. The aim of this study was to
      investigate the spectrum and frequency of these mutations in M. tuberculosis
      clinical isolates, both resistant and susceptible to STR. Sixty-four M.
      tuberculosis isolates recovered from as many TB patients from Poland in 2004 were
      included in the study. Within the sample were 50 multidrug-resistant (32 STR
      resistant and 18 STR-susceptible) and 14 pan-susceptible isolates. Preliminary
      testing for STR resistance was performed with the 1% proportion method. The MICs
      of STR were determined by the Etest method. Mutation profiling was carried out by
      amplifying and sequencing the entire rrs, rpsL, and gidB genes. Non-synonymous
      mutations in either rrs or rpsL gene were detected in 23 (71.9%) of the STR
      resistant and none of the STR-susceptible isolates. Mutations in the gidB gene
      were distributed among 12 (37.5%) STR-resistant and 13 (40.6%) STR-susceptible
      isolates. Four (12.5%) STR-resistant isolates were wild-type at all three loci
      examined. None of the rrs, rpsL or gidB mutations could be linked to low,
      intermediate or high level of STR resistance. In accordance with previous
      findings, the gidB 47T->G (L16R) mutation was associated with the Latin American
      Mediterranean genotype family, whereas 276A->C (E92D) and 615A->G (A205A)
      mutations of the gidB gene were associated with the Beijing lineage. The study
      underlines the usefulness of rrs and rpsL mutations as molecular markers for STR
      resistance yet not indicative of its level. The gidB polymorphisms can serve as
      phylogenetic markers. 

PMID- 24937125
TI  - Point-of-care multiplexed assays of nucleic acids using microcapillary-based loop
      mediated isothermal amplification.
AB  - This report demonstrates a straightforward, robust, multiplexed and point-of-care
      microcapillary-based loop-mediated isothermal amplification (cLAMP) for assaying
      nucleic acids. This assay integrates capillaries (glass or plastic) to introduce
      and house sample/reagents, segments of water droplets to prevent contamination,
      pocket warmers to provide heat, and a hand-held flashlight for a visual readout
      of the fluorescent signal. The cLAMP system allows the simultaneous detection of
      two RNA targets of human immunodeficiency virus (HIV) from multiple plasma
      samples, and achieves a high sensitivity of two copies of standard plasmid. As
      few nucleic acid detection methods can be wholly independent of external power
      supply and equipment, our cLAMP holds great promise for point-of-care
      applications in resource-poor settings. 

PMID- 24937126
TI  - Availability and temporal heterogeneity of water supply affect the vertical
      distribution and mortality of a belowground herbivore and consequently plant
      growth.
AB  - We examined how the volume and temporal heterogeneity of water supply changed the
      vertical distribution and mortality of a belowground herbivore, and consequently
      affected plant biomass. Plantago lanceolata (Plantaginaceae) seedlings were grown
      at one per pot under different combinations of water volume (large or small
      volume) and heterogeneity (homogeneous water conditions, watered every day;
      heterogeneous conditions, watered every 4 days) in the presence or absence of a
      larva of the belowground herbivorous insect, Anomala cuprea (Coleoptera:
      Scarabaeidae). The larva was confined in different vertical distributions to top
      feeding zone (top treatment), middle feeding zone (middle treatment), or bottom
      feeding zone (bottom treatment); alternatively no larva was introduced (control
      treatment) or larval movement was not confined (free treatment). Three-way
      interaction between water volume, heterogeneity, and the herbivore significantly
      affected plant biomass. With a large water volume, plant biomass was lower in
      free treatment than in control treatment regardless of heterogeneity. Plant
      biomass in free treatment was as low as in top treatment. With a small water
      volume and in free treatment, plant biomass was low (similar to that under top
      treatment) under homogeneous water conditions but high under heterogeneous ones
      (similar to that under middle or bottom treatment). Therefore, there was little
      effect of belowground herbivory on plant growth under heterogeneous water
      conditions. In other watering regimes, herbivores would be distributed in the
      shallow soil and reduced root biomass. Herbivore mortality was high with
      homogeneous application of a large volume or heterogeneous application of a small
      water volume. Under the large water volume, plant biomass was high in pots in
      which the herbivore had died. Thus, the combinations of water volume and
      heterogeneity affected plant growth via the change of a belowground herbivore. 

PMID- 24937128
TI  - Available for a limited time only: Regulating gene expression through mRNA
      turnover.

PMID- 24937127
TI  - Expression of orphan receptors GPR22 and GPR162 in streptozotocin-induced
      diabetic rats.
AB  - AIMS/INTRODUCTION: Diabetes mellitus is a chronic degenerative disease
      characterized by high blood glucose levels as a result of problems in the action
      or insulin secretion. Although there are many treatments for this pathology, it
      has been associated with a high mortality rate. For this reason, it is important
      to try to identify new pathways that could be involved in diabetic complications.
      Recently, a new class of receptors has been reported, called orphan receptors
      because the associated ligand and signaling pathways are unknown, these receptors
      have been associated with certain pathologies. Therefore, the aim of this work
      was to study the expression of the orphan receptors GPR22 and GPR162 in heart,
      aorta, brain and kidney of diabetic rats. MATERIALS AND METHODS: We used Wistar
      male rats with 10-12 weeks of age. Diabetes was induced by a single dose of
      streptozotocin (60 mg/kg i.p.). After four weeks, the tissue was obtained and the
      expression of the mRNA was measured by RT-PCR. RESULTS: Our results showed that
      the orphan receptors are expressed in a different way in heart, kidney, brain and
      aorta of diabetic and non-diabetic rats. CONCLUSIONS: We conclude that orphan
      receptors could be involved in the development of diabetes complications.

PMID- 24937129
TI  - Sexual modulation of neural circuits and behavior in Caenorhabditis elegans.
AB  - Sex differences in behavior-both sex-specific and shared behaviors-are
      fundamental to nearly all animal species. One often overlooked mechanism by which
      these behavioral differences can be generated is through sex-specific modulation
      of shared circuitry (i.e., circuits present in both sexes). In vertebrates this
      modulation is likely regulated by hormone-dependent mechanisms as well as by
      somatic sex itself; invertebrate models have particular promise for understanding
      the latter of these. Here we review molecular and behavioral evidence of sexual
      modulation of shared circuitry in the nematode Caenorhabditis elegans. Multiple
      behaviors in this species, both copulatory and not, are modulated by the genetic
      sex of shared neurons and circuit. These studies are close to uncovering the
      molecular mechanisms by which somatic sex modulates neural function in the worm,
      mechanisms which may be well conserved in more complex organisms. Improving our
      understanding of the modulation of neural circuit development and function by
      somatic sex may lend important insight into sex differences in the mammalian
      nervous system which, in turn, may have important implications for sex biases in
      disease. 

PMID- 24937130
TI  - ATM regulates insulin-like growth factor 1-secretory clusterin (IGF-1-sCLU)
      expression that protects cells against senescence.
AB  - Downstream factors that regulate the decision between senescence and cell death
      have not been elucidated. Cells undergo senescence through three pathways,
      replicative senescence (RS), stress-induced premature senescence (SIPS) and
      oncogene-induced senescence. Recent studies suggest that the ataxia
      telangiectasia mutant (ATM) kinase is not only a key protein mediating cellular
      responses to DNA damage, but also regulates cellular senescence induced by
      telomere end exposure (in RS) or persistent DNA damage (in SIPS). Here, we show
      that expression of secretory clusterin (sCLU), a known pro-survival extracellular
      chaperone, is transcriptionally up-regulated during both RS and SIPS, but not in
      oncogene-induced senescence, consistent with a DNA damage-inducible mechanism. We
      demonstrate that ATM plays an important role in insulin-like growth factor 1 (IGF
      1) expression, that in turn, regulates downstream sCLU induction during
      senescence. Loss of ATM activity, either by genomic mutation (ATM-deficient
      fibroblasts from an ataxia telangiectasia patient) or by administration of a
      chemical inhibitor (AAI, an inhibitor of ATM and ATR), blocks IGF-1-sCLU
      expression in senescent cells. Downstream, sCLU induction during senescence is
      mediated by IGF-1R/MAPK/Egr-1 signaling, identical to its induction after DNA
      damage. In contrast, administration of an IGF-1 inhibitor caused apoptosis of
      senescent cells. Thus, IGF-1 signaling is required for survival, whereas sCLU
      appears to protect cells from premature senescence, as IMR-90 cells with sCLU
      knockdown undergo senescence faster than control cells. Thus, the ATM-IGF-1-sCLU
      pathway protects cells from lethality and suspends senescence. 

PMID- 24937131
TI  - The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a
      progressive ratio/chow feeding choice task: reversal with antidepressant drugs.
AB  - Behavioral activation is a fundamental feature of motivation, and organisms
      frequently make effort-related decisions based upon evaluations of reinforcement
      value and response costs. Furthermore, people with major depression and other
      disorders often show anergia, psychomotor retardation, fatigue, and alterations
      in effort-related decision making. Tasks measuring effort-based decision making
      can be used as animal models of the motivational symptoms of depression, and the
      present studies characterized the effort-related effects of the vesicular
      monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces
      depressive symptoms in humans, and also preferentially depletes dopamine (DA).
      Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task,
      in which they can either lever press on a PROG schedule for preferred high
      carbohydrate food, or approach and consume a less-preferred lab chow that is
      freely available in the chamber. Previous work has shown that the DA antagonist
      haloperidol reduced PROG work output on this task, but did not reduce chow
      intake, effects that differed substantially from those of reinforcer devaluation
      or appetite suppressant drugs. The present work demonstrated that tetrabenazine
      produced an effort-related shift in responding on the PROG/chow procedure,
      reducing lever presses, highest ratio achieved and time spent responding, but not
      reducing chow intake. Similar effects were produced by administration of the
      subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by
      the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant
      AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A
      antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor
      bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced
      by tetrabenazine. This work demonstrates the potential utility of the PROG/chow
      procedure as a rodent model of the effort-related deficits observed in depressed
      patients. 

PMID- 24937133
TI  - Bactericidal effect of polyethyleneimine capped ZnO nanoparticles on multiple
      antibiotic resistant bacteria harboring genes of high-pathogenicity island.
AB  - Zinc oxide nanoparticles (ZnO-NP) were synthesized by alcoholic route using zinc
      acetate as the precursor material and lithium hydroxide as hydrolyzing agent.
      Further ZnO-PEI NP (derivative of ZnO-NP) was made in aqueous medium using the
      capping agent polyethyleneimine (PEI). The nanoparticles were characterized by
      XRD measurements, TEM and other techniques; the weight % of coating shell in the
      polymer-capped particles was determined by TGA. ZnO-PEI NP is more soluble in
      water than the uncapped ZnO-NP, and forms a colloidal suspension in water. PEI
      capped ZnO-NP exhibited better antibacterial activity when compared with that of
      uncapped ZnO-NP against a range of multiple-antibiotic-resistant (MAR) Gram
      negative bacterial strains harboring genes of high-pathogenicity island. ZnO-NP
      effectively killed these microorganisms by generating reactive oxygen species
      (ROS) and damaging bacterial membrane. ZnO-PEI NP at LD50 dose in combination
      with tetracycline showed synergistic effect to inhibit tetracycline-resistant
      Escherichia coli MREC33 growth by 80%. These results open up a new vista in
      therapeutics to use antibiotics (which have otherwise been rendered useless
      against MAR bacteria) in combination with minimized dosage of nanoparticles for
      the more effective control of MAR pathogenic bacteria. 

PMID- 24937132
TI  - Structure analysis and conformational transitions of the cell penetrating peptide
      transportan 10 in the membrane-bound state.
AB  - Structure analysis of the cell-penetrating peptide transportan 10 (TP10) revealed
      an exemplary range of different conformations in the membrane-bound state. The
      bipartite peptide (derived N-terminally from galanin and C-terminally from
      mastoparan) was found to exhibit prominent characteristics of (i) amphiphilic
      alpha-helices, (ii) intrinsically disordered peptides, as well as (iii) beta
      pleated amyloid fibrils, and these conformational states become interconverted as
      a function of concentration. We used a complementary approach of solid-state
      (19)F-NMR and circular dichroism in oriented membrane samples to characterize the
      structural and dynamical behaviour of TP10 in its monomeric and aggregated forms.
      Nine different positions in the peptide were selectively substituted with either
      the L- or D-enantiomer of 3-(trifluoromethyl)-bicyclopent-[1.1.1]-1-ylglycine
      (CF3-Bpg) as a reporter group for (19)F-NMR. Using the L-epimeric analogs, a
      comprehensive three-dimensional structure analysis was carried out in lipid
      bilayers at low peptide concentration, where TP10 is monomeric. While the N
      terminal region is flexible and intrinsically unstructured within the plane of
      the lipid bilayer, the C-terminal alpha-helix is embedded in the membrane with an
      oblique tilt angle of ~ 55 degrees  and in accordance with its amphiphilic
      profile. Incorporation of the sterically obstructive D-CF3-Bpg reporter group
      into the helical region leads to a local unfolding of the membrane-bound peptide.
      At high concentration, these helix-destabilizing C-terminal substitutions promote
      aggregation into immobile beta-sheets, which resemble amyloid fibrils. On the
      other hand, the obstructive D-CF3-Bpg substitutions can be accommodated in the
      flexible N-terminus of TP10 where they do not promote aggregation at high
      concentration. The cross-talk between the two regions of TP10 thus exerts a
      delicate balance on its conformational switch, as the presence of the alpha-helix
      counteracts the tendency of the unfolded N-terminus to self-assemble into beta
      pleated fibrils.

PMID- 24937134
TI  - Facilitating neural stem/progenitor cell niche calibration for neural lineage
      differentiation by polyelectrolyte multilayer films.
AB  - Neural stem/progenitor cells (NSPCs) are a possible candidate for advancing
      development and lineage control in neural engineering. Differentiated protocols
      have been developed in this field to generate neural progeny and to establish
      neural networks. However, continued refinement is required to enhance
      differentiation specificity and prevent the generation of unwanted cell types. In
      this study, we fabricated a niche-modulated system to investigate surface effects
      on NSPC differentiation by the formation of polyelectrolyte multilayer (PEM)
      films governed by electrostatic interactions of poly-l-glutamine acid as a
      polyanion and poly-l-lysine as a polycation. The serum- and chemical agent-free
      system provided a clean and clear platform to observe in isolation the
      interaction between surface niche and stem cell differentiation. We found that
      NSPCs were inducible on PEM films of up to eight alternating layers. In addition,
      neurite outgrowth, neuron percentage, and synaptic function were regulated by
      layer number and the surface charge of the terminal layer. The average process
      outgrowth length was over 500MUm on PLL/PLGA(n=7.5) only after 3 days of culture.
      Moreover, the quantity and quality of the differentiated neurons were enhanced as
      the number of layers increased, especially when the terminal layer was poly-l
      lysine. Our results achieve important targets of neural engineering, including
      long processes, large neural network size, and large amounts of functional
      neurons. Our methodology for nanoscale control of material deposition can be
      successfully applied for surface modification, neural niche modulation, and
      neural engineering applications. 

PMID- 24937135
TI  - Itraconazole-hydroxypropyl-beta-cyclodextrin loaded deformable liposomes: in
      vitro skin penetration studies and antifungal efficacy using Candida albicans as
      model.
AB  - The study aimed to develop novel ITZ-loaded deformable liposomes (DL) in presence
      of hydroxypropyl-beta-cyclodextrin (HPbetaCD) (DL-CD) to enhance antifungal
      activity. These formulations have been reported as conceivable vesicles to
      deliver drug molecules to the skin layers. The efficiency of the prepared systems
      was compared with conventional liposomes (CL) and ITZ solution. The developed
      liposomes were characterized for particle size, entrapment efficiency (EE %),
      deformability, stability, and morphology of the vesicles. In addition, ex vivo
      penetration and antifungal activity were evaluated. It was found that the
      presence of HPbetaCD played a significant role in reducing the vesicle size to
      nano range. The deformability study and TEM images revealed that membrane
      deformability of DL and DL-CD was much higher than that of CL. Moreover, DL-CD
      enhanced the amount of ITZ in SC and deeper skin layers compared to DL and CL.
      The antifungal activity of ITZ-loaded deformable liposomes remained intact
      compared to ITZ solution. It can be concluded that deformable liposomes in the
      presence of HPbetaCD may be a promising carrier for effective cutaneous delivery
      of ITZ. 

PMID- 24937137
TI  - Evaluation of skeletal tissue repair, part 1: assessment of novel growth-factor
      releasing hydrogels in an ex vivo chick femur defect model.
AB  - Current clinical treatments for skeletal conditions resulting in large-scale bone
      loss include autograft or allograft, both of which have limited effectiveness. In
      seeking to address bone regeneration, several tissue engineering strategies have
      come to the fore, including the development of growth factor releasing
      technologies and appropriate animal models to evaluate repair. Ex vivo models
      represent a promising alternative to simple in vitro systems or complex,
      ethically challenging in vivo models. We have developed an ex vivo culture system
      of whole embryonic chick femora, adapted in this study as a critical size defect
      model to investigate the effects of novel bone extracellular matrix (bECM)
      hydrogel scaffolds containing spatio-temporal growth factor-releasing
      microparticles and skeletal stem cells on bone regeneration, to develop a viable
      alternative treatment for skeletal degeneration. Alginate/bECM hydrogels combined
      with poly (d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30%
      PDLLGA-PEG-PDLLGA) microparticles releasing VEGF, TGF-beta3 or BMP-2 were placed,
      with human adult Stro-1+ bone marrow stromal cells, into 2mm central segmental
      defects in embryonic chick femurs. Alginate/bECM hydrogels loaded with HSA/VEGF
      or HSA/TGF-beta3 demonstrated a cartilage-like phenotype, with minimal collagen I
      deposition, comparable to HSA-only control hydrogels. The addition of BMP-2
      releasing microparticles resulted in enhanced structured bone matrix formation,
      evidenced by increased Sirius red-stained matrix and collagen expression within
      hydrogels. This study demonstrates delivery of bioactive growth factors from a
      novel alginate/bECM hydrogel to augment skeletal tissue formation and the use of
      an organotypic chick femur defect culture system as a high-throughput test model
      for scaffold/cell/growth factor therapies for regenerative medicine. 

PMID- 24937138
TI  - Tailored order: the mesocrystalline nature of sea urchin teeth.
AB  - We investigated the pattern of crystal co-orientation at different length scales,
      together with variations in chemical composition and nanomechanical properties in
      the teeth of the modern sea urchin Paracentrotus lividus with electron
      backscatter diffraction (EBSD), electron probe microanalysis, energy-dispersive X
      ray spectroscopy and nanoindentation testing. Modern sea urchin teeth are Mg
      dominated calcite composite materials. They are distinctly harder than
      inorganically precipitated calcite. Some parts exceed even the hardness of
      dolomite. The teeth show a structuring of their mechanical properties that can be
      correlated to variations in major element chemical composition, such that their
      hardness is positively correlated to their magnesium contents. Mg/Ca ratio in
      Paracentrotus lividus varies between 10 and 26mol.%. Nanohardness of the tooth
      scatters between 3.5 and >8GPa compared to values of 3.0+/-0.2, 7.3+/-0.1 and
      9.2+/-0.9GPa measured on the (104) planes of inorganic calcite, dolomite and
      magnesite, respectively. High-resolution EBSD shows that major structural units
      and subunits of the tooth of Paracentrotus lividus are tilted to each other by ~3
      5 degrees  and 1-2 degrees , respectively. This indicates that the tooth is not a
      single crystal. With EBSD we can show that the tooth of the sea urchin
      Paracentrotus lividus is a hierarchically assembled biological mesocrystal with a
      mosaic texture. In comparison to the misorientation spread of 0.5 degrees  of
      calcite grown from solution, misorientation in the tooth varies between 2 degrees
      and 4 degrees . Thus, the self-sharpening feature of the tooth is enabled by a
      close interplay of its highly evolved micro- to nanostructure, structural unit
      size variations with a varying degree of crystal orientation, chemical
      structuring of the mineral component and a gradation of incorporated organic
      polymers. 

PMID- 24937136
TI  - HIV among people who inject drugs in the Middle East and North Africa: systematic
      review and data synthesis.
AB  - BACKGROUND: It is perceived that little is known about the epidemiology of HIV
      infection among people who inject drugs (PWID) in the Middle East and North
      Africa (MENA). The primary objective of this study was to assess the status of
      the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence.
      Secondary objectives were to describe the risk behavior environment and the HIV
      epidemic potential among PWID, and to estimate the prevalence of injecting drug
      use in MENA. METHODS AND FINDINGS: This was a systematic review following the
      PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and
      international databases, as well as country-level reports were searched up to
      December 16, 2013. Primary studies reporting (1) the prevalence/incidence of HIV,
      other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or
      (2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among
      PWID; or (3) the number/proportion of PWID in MENA countries, were eligible for
      inclusion. The quality, quantity, and geographic coverage of the data were
      assessed at country level. Risk of bias in predefined quality domains was
      described to assess the quality of available HIV prevalence measures. After
      multiple level screening, 192 eligible reports were included in the review. There
      were 197 HIV prevalence measures on a total of 58,241 PWID extracted from
      reports, and an additional 226 HIV prevalence measures extracted from the
      databases. We estimated that there are 626,000 PWID in MENA (range: 335,000
      1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics
      among PWID in at least one-third of MENA countries, most of which are emerging
      concentrated epidemics and with HIV prevalence overall in the range of 10%-15%.
      Some of the epidemics have however already reached considerable levels including
      some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya).
      The relatively high prevalence of sharing needles/syringes (18%-28% in the last
      injection), the low levels of condom use (20%-54% ever condom use), the high
      levels of having sex with sex workers and of men having sex with men (15%-30% and
      2%-10% in the last year, respectively), and of selling sex (5%-29% in the last
      year), indicate a high injecting and sexual risk environment. The prevalence of
      HCV (31%-64%) and of sexually transmitted infections suggest high levels of risk
      behavior indicative of the potential for more and larger HIV epidemics.
      CONCLUSIONS: Our study identified a large volume of HIV-related biological and
      behavioral data among PWID in the MENA region. The coverage and quality of the
      data varied between countries. There is robust evidence for HIV epidemics among
      PWID in multiple countries, most of which have emerged within the last decade and
      continue to grow. The lack of sufficient evidence in some MENA countries does not
      preclude the possibility of hidden epidemics among PWID in these settings. With
      the HIV epidemic among PWID in overall a relatively early phase, there is a
      window of opportunity for prevention that should not be missed through the
      provision of comprehensive programs, including scale-up of harm reduction
      services and expansion of surveillance systems.

PMID- 24937139
TI  - Bioinspired superamphiphobic surfaces as a tool for polymer- and solvent
      independent preparation of drug-loaded spherical particles.
AB  - Superamphiphobic surfaces were evaluated as a tool to prepare spherical particles
      from polymers and solvents of very diverse nature, under mild conditions and with
      100% drug encapsulation yield. Different from bioinspired superhydrophobic
      surfaces suitable only for aqueous dispersions, the superamphiphobic platforms
      allowed the formation of spherical droplets when solvents of any polarity were
      deposited onto them. Spherical poly(d,l-lactide-co-glycolide) (PLGA) particles
      were synthesized by placing drops of PLGA/ciprofloxacin suspensions in dioxane on
      a superamphiphobic surface followed by solvent evaporation. The particles
      prepared covering a wide range of PLGA/ciprofloxacin weight ratios delivered a
      20% dose in the first 24h and then sustained the release of the remaining drug
      for more than 1month. The particles, both freshly prepared and after being 26days
      in the release medium, showed efficiency against different types of
      microorganisms. The developed polymer- and solvent-independent approach could be
      useful for microencapsulation with very high efficiency of active substances of
      varied nature into size-tunable particles for a wide range of applications in an
      affordable and cost-effective manner. 

PMID- 24937140
TI  - Oldest medical description of a near death experience (NDE), France, 18th
      century.

PMID- 24937141
TI  - X-chromosome inactivation in development and cancer.
AB  - X-chromosome inactivation represents an epigenetics paradigm and a powerful model
      system of facultative heterochromatin formation triggered by a non-coding RNA,
      Xist, during development. Once established, the inactive state of the Xi is
      highly stable in somatic cells, thanks to a combination of chromatin associated
      proteins, DNA methylation and nuclear organization. However, sporadic
      reactivation of X-linked genes has been reported during ageing and in transformed
      cells and disappearance of the Barr body is frequently observed in cancer cells.
      In this review we summarise current knowledge on the epigenetic changes that
      accompany X inactivation and discuss the extent to which the inactive X
      chromosome may be epigenetically or genetically perturbed in breast cancer. 

PMID- 24937143
TI  - Surface topology assisted alignment of Min protein waves.
AB  - Self-organization of proteins into large-scale structures is of pivotal
      importance for the organization of cells. The Min protein system of the bacterium
      Escherichia coli is a prime example of how pattern formation occurs via reaction
      diffusion. We have previously demonstrated how Min protein patterns are
      influenced by compartment geometry. Here we probe the influence of membrane
      surface topology, as an additional regulatory element. Using microstructured
      membrane-clad soft polymer substrates, Min protein patterns can be aligned. We
      demonstrate that Min pattern alignment starts early during pattern formation and
      show that macroscopic millimeter-sized areas of protein patterns of well-defined
      orientation can be generated. 

PMID- 24937144
TI  - Arabidopsis thaliana plastoglobule-associated fibrillin 1a interacts with
      fibrillin 1b in vivo.
AB  - Plant fibrillins are a well-conserved protein family found in the plastids of all
      photosynthetic organisms, where they perform a wide range of functions. A number
      of these proteins have been suggested to be involved in the maintenance of
      thylakoids and the formation of plastoglobules, preventing their coalescence and
      favoring their clustering via an as-yet unidentified cross-linking mechanism. In
      this work we show that two members of this group, namely fibrillin 1a and 1b,
      interact with each other via a head-to-tail mechanism, thus raising the
      possibility that they form homo- or hetero-oligomers and providing a mechanism to
      understand the function of these proteins. 

PMID- 24937142
TI  - "RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.
AB  - The Raf/Mek/Erk signaling pathway, activated downstream of Ras primarily to
      promote proliferation, represents the best studied of the evolutionary conserved
      MAPK cascades. The investigation of the pathway has continued unabated since its
      discovery roughly 30 years ago. In the last decade, however, the identification
      of unexpected in vivo functions of pathway components, as well as the discovery
      of Raf mutations in human cancer, the ensuing quest for inhibitors, and the
      efforts to understand their mechanism of action, have boosted interest
      tremendously. From this large body of work, protein-protein interaction has
      emerged as a recurrent, crucial theme. This review focuses on the role of protein
      complexes in the regulation of the Raf/Mek/Erk pathway and in its cross-talk with
      other signaling cascades. Mapping these interactions and finding a way of
      exploiting them for therapeutic purposes is one of the challenges of future
      molecule-targeted therapy.

PMID- 24937145
TI  - High-speed atomic force microscopy: imaging and force spectroscopy.
AB  - Atomic force microscopy (AFM) is the type of scanning probe microscopy that is
      probably best adapted for imaging biological samples in physiological conditions
      with submolecular lateral and vertical resolution. In addition, AFM is a method
      of choice to study the mechanical unfolding of proteins or for cellular force
      spectroscopy. In spite of 28 years of successful use in biological sciences, AFM
      is far from enjoying the same popularity as electron and fluorescence microscopy.
      The advent of high-speed atomic force microscopy (HS-AFM), about 10 years ago,
      has provided unprecedented insights into the dynamics of membrane proteins and
      molecular machines from the single-molecule to the cellular level. HS-AFM imaging
      at nanometer-resolution and sub-second frame rate may open novel research fields
      depicting dynamic events at the single bio-molecule level. As such, HS-AFM is
      complementary to other structural and cellular biology techniques, and hopefully
      will gain acceptance from researchers from various fields. In this review we
      describe some of the most recent reports of dynamic bio-molecular imaging by HS
      AFM, as well as the advent of high-speed force spectroscopy (HS-FS) for single
      protein unfolding.

PMID- 24937147
TI  - Treatment progress indicator: application of a new assessment tool to objectively
      monitor the therapeutic progress of patients with depression, anxiety, or
      behavioral health impairment.
AB  - Depression, anxiety, and behavioral health impairment are common in the US.
      Efforts to treat patients with depression, anxiety, and chemical dependency are
      surpassed by the great demand for psychiatrist and therapist appointments. Unlike
      other specialties, psychiatry lacks a vital sign or tests (eg, blood pressure for
      hypertension and hemoglobin A1c for diabetes) to objectively measure a patient's
      response to therapy. A new tool called the Treatment Progress Indicator (TPI)
      appears to offer clinicians an objective approach to assess patients and to
      monitor therapy over time. The TPI report shows an Expected Treatment Response
      that allows clinicians to compare their patients' responses to therapy with those
      of a cohort of patients with a similar diagnosis and severity. The TPI allows for
      objective population-level management of disease. This should result in sharing
      of best practices that will lead to more effective and efficient care plans.
      Widespread implementation of the TPI has the potential to improve the time
      required to diagnose conditions and triage patients. As a result, implementation
      of the tool has the potential to improve behavioral health access and
      affordability.

PMID- 24937146
TI  - Targeting Alp7/TACC to the spindle pole body is essential for mitotic spindle
      assembly in fission yeast.
AB  - The conserved TACC protein family localises to the centrosome (the spindle pole
      body, SPB in fungi) and mitotic spindles, thereby playing a crucial role in
      bipolar spindle assembly. However, it remains elusive how TACC proteins are
      recruited to the centrosome/SPB. Here, using fission yeast Alp7/TACC, we have
      determined clustered five amino acid residues within the TACC domain required for
      SPB localisation. Critically, these sequences are essential for the functions of
      Alp7, including proper spindle formation and mitotic progression. Moreover, we
      have identified pericentrin-like Pcp1 as a loading factor to the mitotic SPB,
      although Pcp1 is not a sole platform. 

PMID- 24937148
TI  - An adaptation of family-based behavioral pediatric obesity treatment for a
      primary care setting: group health family wellness program pilot.
AB  - OBJECTIVE: To assess the feasibility and acceptability of family-based group
      pediatric obesity treatment in a primary care setting, to obtain an estimate of
      its effectiveness, and to describe participating parents' experiences of social
      support for healthy lifestyle changes. METHODS: We adapted an evidence-based
      intervention to a group format and completed six 12- to 16-week groups over 3
      years. We assessed program attendance and completion, changes in child and parent
      body mass index (BMI; calculated as weight in kilograms divided by height in
      meters squared), and changes in child quality of life in a single-arm before-and
      after trial. Qualitative interviews explored social support for implementing
      healthy lifestyle changes. RESULTS: Thirty-eight parent-child pairs enrolled (28%
      of the 134 pairs invited). Of those, 24 (63%) completed the program and another 6
      (16%) attended at least 4 sessions but did not complete the program. Children who
      completed the program achieved a mean change in BMI Z-scores (Z-BMI) of -0.1
      (0.1) (p < 0.001) and significant improvement in parent-reported child quality of
      life (mean change = 8.5; p = 0.002). Mean BMI of parents changed by -0.9 (p =
      0.003). Parents reported receiving a wide range of social support for healthy
      lifestyle changes and placed importance on the absence or presence of support.
      CONCLUSIONS: A pilot group program for family-based treatment of pediatric
      obesity is feasible and acceptable in a primary care setting. Change in child and
      parent BMI outcomes and child quality of life among completers were promising
      despite the pilot's low intensity. Parent experiences with lack of social support
      suggest possible ways to improve retention and adherence.

PMID- 24937149
TI  - Successful practices in the use of secure e-mail.
AB  - Physician use of secure e-mail with patients is anticipated to increase under
      Stage 2 Meaningful Use requirements, but little is known about how physicians can
      successfully incorporate it into daily work. We interviewed 27 "super user"
      physicians at Kaiser Permanente and Group Health who were identified by leaders
      as being technologically, operationally, and clinically adept and as having high
      levels of secure e-mail use with patients. They highly valued the use of secure e
      mail with patients, despite concerns about a lack of adequate time to respond,
      and provided tips for using it successfully. They identified benefits that
      included better care and improved relationships with their patients.

PMID- 24937151
TI  - Improving care for older adults: a model to segment the senior population.
AB  - CONTEXT: Risk stratification and tailored interventions are key population-level
      care management strategies among older adults, whose needs range from screening
      and prevention to end-of-life care. OBJECTIVE: To validate the Senior
      Segmentation Algorithm, a tool using administrative and clinical data from the
      electronic health record to identify each member aged 65 years and older as
      belonging to 1 of 4 Care Groups with similar needs: those without chronic
      conditions, with one or more chronic conditions, with advanced illness or end
      organ failure, or with extreme frailty or nearing the end of life. DESIGN:
      Multiple validation methods. MAIN OUTCOME MEASURES: Concordance with physician
      judgment, stability of segmentation over time, convergence with mortality,
      hospitalization, and readmission rates, and costs of care. RESULTS: Concordance
      of the algorithm with physician-assessed segmentation of 1615 Medicare recipients
      was 85%. After 1 year, approximately 85% of 86,140 surviving seniors remained in
      the same care group; 3.9% moved to a lower need group; and 11% moved to a higher
      need group. Six-month and 12-month mortality rates varied substantially across
      care groups. The algorithm performed similarly to the likelihood of
      hospitalization score in predicting hospitalization and readmissions.
      CONCLUSIONS: The Senior Segmentation Algorithm accurately identifies older adults
      in care groups with similar needs, trajectories, and utilization patterns. It is
      being implemented in all Kaiser Permanente Regions, with the goal of determining
      key elements of care for members in each group. In addition, future efforts will
      aim to slow progression to higher need care groups and to identify necessary
      improvements in delivery system design.

PMID- 24937152
TI  - A commentary on "comparative health systems research among Kaiser Permanente and
      other integrated delivery systems: a systematic literature review".

PMID- 24937150
TI  - Comparative health systems research among Kaiser Permanente and other integrated
      delivery systems: a systematic literature review.
AB  - CONTEXT: Because of rising health care costs, wide variations in quality, and
      increased patient complexity, the US health care system is undergoing rapid
      changes that include payment reform and movement toward integrated delivery
      systems. Well-established integrated delivery systems, such as Kaiser Permanente
      (KP), should work to identify the specific system-level factors that result in
      superior patient outcomes in response to policymakers' concerns. Comparative
      health systems research can provide insights into which particular aspects of the
      integrated delivery system result in improved care delivery. OBJECTIVE: To
      provide a baseline understanding of comparative health systems research related
      to integrated delivery systems and KP. DESIGN: Systematic literature review.
      METHODS: We conducted a literature search on PubMed and the KP Publications
      Library. Studies that compared KP as a system or organization with other health
      care systems or across KP facilities internally were included. The literature
      search identified 1605 articles, of which 65 met the study inclusion criteria and
      were examined by 3 reviewers. RESULTS: Most comparative health systems studies
      focused on intra-KP comparisons (n = 42). Fewer studies compared KP with other US
      (n = 15) or international (n = 12) health care systems. Several themes emerged
      from the literature as possible factors that may contribute to improved care
      delivery in integrated delivery systems. CONCLUSIONS: Of all studies published by
      or about KP, only a small proportion of articles (4%) was identified as being
      comparative health systems research. Additional empirical studies that compare
      the specific factors of the integrated delivery system model with other systems
      of care are needed to better understand the "system-level" factors that result in
      improved and/or diminished care delivery.

PMID- 24937153
TI  - TERT promoter mutations lead to high transcriptional activity under hypoxia and
      temozolomide treatment and predict poor prognosis in gliomas.
AB  - OBJECTIVE: This study explored the effects of telomerase reverse transcriptase
      (TERT) promoter mutations on transcriptional activity of the TERT gene under
      hypoxic and temozolomide (TMZ) treatment conditions, and investigated the status
      and prognostic value of these mutations in gliomas. METHODS: The effect of TERT
      promoter mutations on the transcriptional activity of the TERT gene under hypoxic
      and TMZ treatment conditions was investigated in glioma cells using the
      luciferase assay. TERT promoter mutations were detected in 101 glioma samples
      (grades I-IV) and 49 other brain tumors by sequencing. TERT mRNA expression in
      gliomas was examined by real-time PCR. Hazard ratios from survival analysis of
      glioma patients were determined relative to the presence of TERT promoter
      mutations. RESULTS: Mutations in the TERT promoter enhanced gene transcription
      even under hypoxic and TMZ treatment conditions, inducing upregulation of TERT
      mRNA expression. Mutations were detected in gliomas, but not in meningiomas,
      pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or
      peripheral blood of glioma patients. Patients with TERT promoter mutations had
      lower survival rates, even after adjusting for other known or potential risk
      factors, and the incidence of mutation was correlated with patient age.
      CONCLUSION: TERT promoter mutations were specific to gliomas. TERT promoter
      mutations maintained its ability of inducing high transcriptional activity even
      under hypoxic and TMZ treatment conditions, and the presence of mutations was
      associated with poor prognosis in glioma patients. These findings demonstrate
      that TERT promoter mutations are novel prognostic markers for gliomas that can
      inform prospective therapeutic strategies.

PMID- 24937154
TI  - Genetic stability developed for beta-carotene synthesis in BR29 rice line using
      dihaploid homozygosity.
AB  - Obtaining transgenic crop lines with stable levels of carotenoids is highly
      desirable. We addressed this issue by employing the anther culture technique to
      develop dihaploid lines containing genes involved in beta-carotene metabolism.
      First, we used Agrobacterium- mediated transformation to develop primary
      transgenic plants containing the beta-carotene biosynthetic genes, phytoene
      synthase (psy) and phytoene desaturase (crtI), which were engineered for
      expression and accumulation in the endosperm. Transgenic plants were recovered by
      selecting for the expression of the phosphomannose isomerase (pmi) gene.
      Dihaploid plants in addition to haploid and tetraploid plant were generated from
      anther cultures of these primary transgenic plants. In addition to anatomical
      features of stomata, pollen of different ploidy-plants, molecular analyses
      confirmed the stable integration of the genes in the anther culture-derived
      dihaploid plants, and the yellow color of the polished seeds indicated the
      accumulation of carotenoids in the endosperm. High performance liquid
      chromatography (HPLC) analysis of the carotenoid extract further confirmed the
      levels of beta-carotene accumulation in the endosperms of the transgenic
      dihaploid rice seeds. 

PMID- 24937155
TI  - Effects of road dust suppressants on PM levels in a Mediterranean urban area.
AB  - The abatement of road dust emissions is currently a major challenge for
      sustainable transportation, causing exceedances of limits on particulate matter
      (PM) and high population exposures to mineral dust and metals. Mitigation
      measures have been proposed such as improved street cleaning and the use of dust
      suppressants. This study evaluated, for the first time, the effectiveness of
      calcium-magnesium acetate (CMA) and MgCl2 in reducing road dust emissions in a
      Mediterranean city. During a two-month campaign, a typical urban road in the city
      of Barcelona was sprayed, and changes in PMx levels and components were monitored
      at four traffic sites and one background monitoring sites. The integrated results
      indicate no statistically significant effectiveness of dust suppressants on PM10
      and PM2.5-10 levels. Episodic reductions of Al, K, Mg, Cr, Li, Cu, and Zn were
      observed during CMA applications, but they were not systematically statistically
      significant over different stations and spreading days. MgCl2 days showed lower
      PM10 mean concentrations, but these reductions were not statistically significant
      and were not supported by significant drops in mineral and brake-wear metals.
      Based on our literature review, it can be postulated that the higher the road
      dust loading, the higher the dust suppressant effectiveness. 

PMID- 24937156
TI  - Misconceptions and facts about 'diastolic' heart failure.
AB  - Heart failure with preserved ejection fraction has become a fashionable
      diagnosis. An increasing number of elderly patients with dyspnea carry this
      diagnosis. Evaluation and management of these patients typically labeled as
      having "diastolic" heart failure are challenging, and misconceptions are common.
      No drug class has been shown to consistently provide outcome benefit. Therapeutic
      strategies based on the predominant pathophysiologic mechanism and stage of the
      disease currently remain the best option in tackling the perplexing syndrome of
      heart failure with preserved ejection fraction. 

PMID- 24937157
TI  - Hemoconcentration-guided diuresis in heart failure.
AB  - One quarter of patients hospitalized for heart failure are readmitted within 30
      days, perhaps related to ineffective decongestion. Limited data exist guiding the
      extent and duration of diuresis in patients hospitalized for heart failure. The
      objective of this review was to determine the prognostic value of
      hemoconcentration, or the relative increase in the cellular elements in blood, in
      patients hospitalized for heart failure and to clarify its role in guiding
      inpatient diuretic practices. Six post hoc retrospective studies from 2010 to
      2013 were available for review. Hemoconcentration was consistently associated
      with markers of aggressive fluid removal, including higher diuretic dosing and
      reduced body weight, but increased risk of in-hospital worsening renal function.
      Despite this, hemoconcentration was associated with improved short-term mortality
      and rehospitalization. Hemoconcentration is a practical, readily available,
      noninvasive, economically feasible strategy to help guide diuresis and monitor
      congestion relief in patients hospitalized for worsening heart failure.
      Clinicians should strongly consider using changes in hemoglobin and hematocrit as
      an adjunct to other available measures of decongestion and clinical acumen in
      inpatient heart failure care.

PMID- 24937159
TI  - Summertime acute heat illness in U.S. emergency departments from 2006 through
      2010: analysis of a nationally representative sample.
AB  - BACKGROUND: Patients with acute heat illness present primarily to emergency
      departments (EDs), yet little is known regarding these visits. OBJECTIVE: We
      aimed to describe acute heat illness visits to U.S. EDs from 2006 through 2010
      and identify factors associated with hospital admission or with death in the ED.
      METHODS: We extracted ED case-level data from the Nationwide Emergency Department
      Sample (NEDS) for 2006-2010, defining cases as ED visits from May through
      September with any heat illness diagnosis (ICD-9-CM 992.0-992.9). We correlated
      visit rates and temperature anomalies, analyzed demographics and ED disposition,
      identified risk factors for adverse outcomes, and examined ED case fatality rates
      (CFR). RESULTS: There were 326,497 (95% CI: 308,372, 344,658) cases, with 287,875
      (88.2%) treated and released, 38,392 (11.8%) admitted, and 230 (0.07%) died in
      the ED. Heat illness diagnoses were first-listed in 68%. 74.7% had heat
      exhaustion, 5.4% heat stroke. Visit rates were highly correlated with annual
      temperature anomalies (Pearson correlation coefficient 0.882, p = 0.005). Treat
      and-release rates were highest for younger adults (26.2/100,000/year), whereas
      hospitalization and death-in-the-ED rates were highest for older adults (6.7 and
      0.03/100,000/year, respectively); all rates were highest in rural areas. Heat
      stroke had an ED CFR of 99.4/10,000 (95% CI: 78.7, 120.1) visits and was
      diagnosed in 77.0% of deaths. Adjusted odds of hospital admission or death in the
      ED were higher among elders, males, urban and low-income residents, and those
      with chronic conditions. CONCLUSIONS: Heat illness presented to the ED
      frequently, with highest rates in rural areas. Case definitions should include
      all diagnoses. Visit rates were correlated with temperature anomalies. Heat
      stroke had a high ED CFR. Males, elders, and the chronically ill were at greatest
      risk of admission or death in the ED. Chronic disease burden exponentially
      increased this risk.

PMID- 24937160
TI  - Clarification of P-glycoprotein inhibition-related drug-drug interaction risks
      based on a literature search of the clinical information.
AB  - 1. Recently, the Food and Drug Administration (FDA) and European Medicines Agency
      have shown decision trees to determine whether a drug candidate is an inhibitor
      of P-glycoprotein (P-gp). However, there has been no clear information on whether
      P-gp inhibition can be significant in clinical drug-drug interactions (DDIs). The
      purpose of this study was to confirm the effect of P-gp inhibition through
      comprehensive analysis of the clinical DDI studies. 2. Clinical information on P
      gp inhibition was collected using the University of Washington Metabolism and
      Transport Drug Interaction DatabaseTM. The risks of P-gp inhibition-related DDI
      were qualitatively evaluated in terms of the contribution of CYP3A inhibition.
      The degrees of DDI risk were categorized using the area under the plasma
      concentration-time curve increase ratio (AUCR), according to the FDA DDI
      criteria. 3. When both P-gp and CYP3A were inhibited, the DDI risks were potent
      in 25% of the studies. When CYP3A inhibition did not contribute to the DDI, no
      study was categorized as potent DDI risk, and the detailed analysis revealed that
      AUCRs were basically <3.0. The DDI risk caused by P-gp inhibition solely would be
      limited, although the use of P-gp substrates with narrow therapeutic range should
      be carefully controlled.

PMID- 24937161
TI  - Patterns of use of medical cannabis among Israeli cancer patients: a single
      institution experience.
AB  - CONTEXT: The use of the cannabis plant (Cannabis sativa L.) for the palliative
      treatment of cancer patients has been legalized in multiple jurisdictions
      including Israel. Yet, not much is currently known regarding the efficacy and
      patterns of use of cannabis in this setting. OBJECTIVES: To analyze the
      indications for the administration of cannabis among adult Israeli cancer
      patients and evaluate its efficacy. METHODS: Efficacy and patterns of use of
      cannabis were evaluated using physician-completed application forms, medical
      files, and a detailed questionnaire in adult cancer patients treated at a single
      institution. RESULTS: Of approximately 17,000 cancer patients seen, 279 (<1.7%)
      received a permit for cannabis from an authorized institutional oncologist. The
      median age of cannabis users was 60 years (range 19-93 years), 160 (57%) were
      female, and 234 (84%) had metastatic disease. Of 151 (54%) patients alive at six
      months, 70 (46%) renewed their cannabis permit. Renewal was more common among
      younger patients and those with metastatic disease. Of 113 patients alive and
      using cannabis at one month, 69 (61%) responded to the detailed questionnaire.
      Improvement in pain, general well-being, appetite, and nausea were reported by
      70%, 70%, 60%, and 50%, respectively. Side effects were mild and consisted mostly
      of fatigue and dizziness. CONCLUSION: Cannabis use is perceived as highly
      effective by some patients with advanced cancer and its administration can be
      regulated, even by local authorities. Additional studies are required to evaluate
      the efficacy of cannabis as part of the palliative treatment of cancer patients.

PMID- 24937158
TI  - Package of NDV-pseudotyped HIV-Luc virus and its application in the
      neutralization assay for NDV infection.
AB  - Newcastle disease virus (NDV) is a member of the Paramyxovirinae subfamily and
      can infect most species of birds. It has been a great threat for the poultry
      industry all around the world. In this report, we successfully produced
      infectious pseudotyped pNL4-3-Luc-R(-)E(-) (HIV-Luc) viruses with the HN and F
      envelope proteins of NDV. Further investigation revealed the cytoplasmic domains
      of HN and F, especially HN, plays a significant role in the infection efficiency
      of these pseudotyped HIV-Luc viruses. Replacement of, or direct fusion to the
      cytoplasmic domain of the HN protein by that of vesicular stomatitis virus G (VSV
      G) could greatly enhance or destroy the infective potential of HN and F
      pseudotyped (NDV-pseudotyped) HIV-Luc virus. We further established a novel
      neutralization assay to evaluate neutralizing antibodies against NDV with the NDV
      pseudotyped HIV-Luc viruses. Comparative neutralization data indicate that the
      results determined by using the NDV-pseudotyped HIV-Luc viruses are as reliable
      as those by the conventional virus-neutralization assay (VN test) with native
      NDV. Moreover, the results show that the novel neutralization assay is more
      sensitive than the VN test.

PMID- 24937162
TI  - Propensity scores: a practical method for assessing treatment effects in pain and
      symptom management research.
AB  - When conducting research on pain and symptom management interventions for
      seriously ill individuals, randomized controlled trials are not always feasible
      or ethical to conduct. Secondary analyses of observational data sets that include
      information on treatments experienced and outcomes for individuals who did and
      did not receive a given treatment can be conducted, but confounding because of
      selection bias can obscure the treatment effect in which one is interested.
      Propensity scores provide a way to adjust for observable characteristics that
      differ between treatment and comparison groups. This article provides conceptual
      guidance in addition to an empirical example to illustrate two areas of
      propensity score analysis that often lead to confusion in practice: covariate
      selection and interpretation of resultant treatment effects. 

PMID- 24937163
TI  - Thalidomide therapy for pruritus in the palliative setting--a distinct subset of
      patients in whom the benefit may outweigh the risk.

PMID- 24937164
TI  - Meaning in life experience at the end of life: validation of the Hindi version of
      the Schedule for Meaning in Life Evaluation and a cross-cultural comparison
      between Indian and German palliative care patients.
AB  - CONTEXT: The experience of Meaning in Life (MiL) is a major protective factor
      against feelings of hopelessness and wishes for hastened death in palliative care
      (PC) patients. However, most instruments for MiL assessment have been developed
      only in Western countries so far. Little is known about MiL experience in Asian
      PC patients. OBJECTIVES: This study aimed to provide a Hindi version of the
      Schedule for Meaning in Life Evaluation (SMiLE), test its feasibility and
      validity in Indian PC patients, and compare the results with previous studies in
      Germany. METHODS: Indian PC patients in a hospice for the destitute were eligible
      to participate in this cross-sectional study. In the SMiLE instrument,
      respondents individually listed MiL-giving areas before rating their satisfaction
      with and importance of these areas. Overall indices of satisfaction (IoS, range 0
      100), weighting (IoW, range 0-100), and weighted satisfaction (IoWS, range 0-100)
      were calculated. RESULTS: A Hindi forward-backward translation of the SMiLE was
      made. Two hundred fifty-eight Indian PC patients took part in the study (response
      rate 93.5%). Convergent validity of the SMiLE was found with the World Health
      Organization Quality of Life-Brief version (r = 0.17; P = 0.008) and the Idler
      Index of Religiosity (public religiousness: r = 0.25, P < 0.001 and private
      religiousness: r = 0.29, P < 0.001). Indian PC patients' IoW was 65.8 +/- 22.1,
      IoS 68.6 +/- 17.4, and IoWS 70.2 +/- 17.0. In multivariate analyses of
      covariance, they differed significantly from German PC patients only in IoW (IoW:
      84.8 +/- 11.5, P < 0.001; IoS: 70.2 +/- 19.7; IoWS: 72.0 +/- 19.4). Compared with
      Germans, Indians more often listed spirituality (P < 0.001) and social commitment
      (P < 0.001) and less often social relations (P = 0.008). CONCLUSION: Preliminary
      results indicate good feasibility and validity of the Hindi version of the SMiLE.
      MiL experience also seems to be a coping resource for Indian PC patients.

PMID- 24937165
TI  - Normal vital signs as death approaches: commentary on Bruera et al.

PMID- 24937166
TI  - An exceptionally fast homogeneous carbon-free cobalt-based water oxidation
      catalyst.
AB  - An all-inorganic, oxidatively and thermally stable, homogeneous water oxidation
      catalyst based on redox-active (vanadate(V)-centered) polyoxometalate ligands,
      Na10[Co4(H2O)2(VW9O34)2].35H2O (Na101-V2, sodium salt of the polyanion 1-V2), was
      synthesized, thoroughly characterized and shown to catalyze water oxidation in
      dark and visible-light-driven conditions. This synthetic catalyst is
      exceptionally fast under mild conditions (TOF > 1 * 10(3) s(-1)). Under light
      driven conditions using [Ru(bpy)3](2+) as a photosensitizer and persulfate as a
      sacrificial electron acceptor, 1-V2 exhibits higher selectivity for water
      oxidation versus bpy ligand oxidation, the final O2 yield by 1-V2 is twice as
      high as that of using [Co4(H2O)2(PW9O34)2](10-) (1-P2), and the quantum
      efficiency of O2 formation at 6.0 MUM 1-V2 reaches ~68%. Multiple experimental
      results (e.g., UV-vis absorption, FT-IR, (51)V NMR, dynamic light scattering,
      tetra-n-heptylammonium nitrate-toluene extraction, effect of pH, buffer, and
      buffer concentration, etc.) confirm that the polyanion unit (1-V2) itself is the
      dominant active catalyst and not Co(2+)(aq) or cobalt oxide. 

PMID- 24937167
TI  - Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year
      follow-up.
AB  - PURPOSE: The aim of this study was to assess the efficacy of accelerated
      crosslinking (irradiance of 9 mW/cm; 10 minutes) in keratoconus-affected eyes
      through topographical, visual, and refractive end points. METHODS: Mild-moderate
      keratoconus-affected eyes that underwent accelerated corneal collagen
      crosslinking (CXL) treatment and had 6 and 12 months of follow-up were reviewed
      retrospectively. Data regarding uncorrected distance visual acuity (UDVA),
      manifest refraction, corrected distance visual acuity (CDVA), and computerized
      corneal topography data before surgery and post-CXL treatment were extracted and
      analyzed. RESULTS: Sixteen eyes of 14 patients were included in the study. The
      mean patient age was 24.9 +/- 5.8 years (range: 17.1-38.3 years). No
      statistically significant changes were found in the mean CDVA, mean refractive
      cylinder, or mean manifest refraction spherical equivalent at either time point.
      There was a gain of 0.13 logarithm of the minimum angle of resolution lines in
      the mean UDVA (P = 0.012) at 12 months. All corneal parameters including Ksteep,
      Kflat, average K (Km), corneal astigmatism (Kcyl), and maximal curvature reading
      at the corneal apex (Kmax) were stable at 6 and 12 months in all patients. No
      complications were observed during the follow-up period. CONCLUSIONS: Accelerated
      corneal CXL is effective in stabilizing topographic parameters after 12 months of
      follow-up in mild-moderate keratoconus-affected corneas. Improvement in the UDVA
      and stabilization of all tested corneal parameters were noted after the
      treatment. However, a longer follow-up with larger cohorts is necessary to
      validate these findings.

PMID- 24937168
TI  - Polymicrobial sclerokeratitis caused by Scedosporium apiospermum and Aspergillus
      cibarius.
AB  - PURPOSE: The aim of this study was to report the first case of polymicrobial
      fungal sclerokeratitis caused by infection with both Scedosporium apiospermum and
      Aspergillus cibarius, and notify the medical community of the possibility of
      infection caused by A. cibarius in humans. METHODS: A 78-year-old woman presented
      to a medical practitioner with epiphora and a purulent discharge in her left eye.
      After concurrent administration of topical antibiotics and systemic steroids, her
      symptoms worsened, and she was referred to the Tokushima University Hospital.
      Because of suspected fungal infection, microscopic examination and cultivation of
      both corneal and scleral scrapings were performed. RESULTS: Fungi were observed
      on microscopic examination, and S. apiospermum was isolated only from the sclera
      in the early stage of the clinical course. Although administration of an adequate
      medication regimen comprising topical and systemic antifungal drugs resulted in
      an improvement in the sclera, keratitis persisted, and the infected sclera was
      melted. After scleral transplantation, administration of systemic caspofungin and
      high concentrations of voriconazole solution eye drops resulted in a gradual
      improvement in keratitis. A strain of filamentous fungus was isolated from the
      cornea 6 weeks after the cultivation on a Sabouraud agar plate, and it was
      identified as A. cibarius. CONCLUSIONS: A. cibarius may infect human tissue.
      Coinfection of the cornea and the sclera with 2 different species of fungi is
      likely to follow a complex clinical course.

PMID- 24937169
TI  - Combined topical application of a regenerative agent with a bandage contact lens
      for the treatment of persistent epithelial defects.
AB  - PURPOSE: The aim of this study was to report 3 cases of persistent epithelial
      defects (PEDs) successfully treated with the combined topical application of a
      regenerative agent (RGTA; Cacicol20, OTR3, Paris, France) with a bandage contact
      lens (BCL). METHODS: This is a case series. RESULTS: Three patients suffering
      from a PED for 4-8 weeks and unresponsive to conventional therapy were treated
      with the combined application of an RGTA (Cacicol20) and a silicone hydrogel BCL.
      The PED healed in all patients after 4-21 days, and no side effects were noted.
      CONCLUSIONS: The combination of an RGTA (Cacicol20) with a BCL seems to be an
      effective treatment for PED.

PMID- 24937170
TI  - Chromosome instability in mouse embryonic stem cells.
AB  - Embryonic Stem Cells (ESCs) are expected to show a stable euploid karyotype, but
      in the last decade (sub)chromosomal aberrations have been systematically
      described in these cell lines when maintained in vitro. Culture conditions and
      long-term culture have been traditionally proposed as possible factors involved
      in the acquisition of chromosomal abnormalities. Thus, we analyzed the chromosome
      constitution, the undifferentiated state and the functional pluripotency of three
      different mouse ESCs grown under the same culture conditions. Two cell lines were
      unstable from early passages, whereas the third one retained its chromosome
      integrity after long-term culture despite using enzymatic methods for cell
      disaggregation. Trisomy 8 and 11 were clonally selected in both unstable cell
      lines, which also showed a higher growth rate than our normal cell line and
      suffered morphological changes in colony shape with increasing passage number.
      Regardless of the length of culture or the chromosome instability, all cell lines
      preserved their differentiation potential. These results confirm that double
      trisomy 8 and 11 confers a growth advantage to the abnormal cells, but not at the
      expense of cell differentiation. The presence of chromosome instability, widely
      related to tumor development and cancer disease, highlights the risk of using
      pluripotent cells in regenerative medicine. 

PMID- 24937172
TI  - Prediabetes, diabetes, and risk of breast cancer: a case-control study.
AB  - BACKGROUND AND AIMS: Although underlying mechanisms have been described to
      account for the association between prediabetes and diabetes with breast cancer,
      reported results have been inconsistent. We undertook this study to determine
      whether prediabetes and diabetes are risk factors for breast cancer in Mexican
      women with no family history of breast cancer in the mother, daughters, or
      sisters. METHODS: A case-control study was carried out during 2011-2013. "Case"
      referred to patients with a histopathological diagnosis of breast cancer
      (incident and primary cases) (n = 240); "controls" were those with a BI-RADS 1 or
      2 mammography result (n = 406). Categorization of prediabetes and diabetes was
      based on self-reporting or fasting glucose and glycated hemoglobin blood sampling
      results. Reproductive and sociodemographic data were collected by interview. Odds
      ratios (ORs) and 95% confidence intervals (CI) were calculated using multivariate
      unconditional binary logistic regression analysis. RESULTS: Prediabetes increased
      the risk of breast cancer in postmenopausal women (adjusted OR 2.08, 95% CI 1.10
      3.96) as did diabetes (adjusted OR 2.85, 95% CI 1.55-5.26). A history of diabetes
      preceding breast cancer by >=7 years and <7 years were both associated with an
      increased risk for breast cancer (adjusted OR 2.80, 95% CI 1.40-5.60 and 3.00,
      95% CI 1.50-5.90, respectively). CONCLUSIONS: This is the first study in Mexico
      evaluating prediabetes and diabetes as breast cancer risk factors in women with
      no first-degree relatives with breast cancer. Our findings suggest that women
      with prediabetes and diabetes should be considered a more vulnerable population
      for early breast cancer detection.

PMID- 24937171
TI  - ERBB2 increases metastatic potentials specifically in androgen-insensitive
      prostate cancer cells.
AB  - Despite all the blood-based biomarkers used to monitor prostate cancer patients,
      prostate cancer remains as the second common cause of cancer mortality in men in
      the United States. This is largely due to a lack of understanding of the
      molecular pathways that are responsible for the aggressive forms of prostate
      cancers, the castrate-resistant prostate cancer and the metastatic prostate
      cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS
      oncogene are frequently found to be altered in metastatic prostate cancers. To
      evaluate and define the role of the ERBB2/RAS pathway in prostate cancer
      metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the
      metastatic potentials for four prostate cancer cell lines derived from tumors
      with different androgen sensitivities. To do so, we transfected the human DU145,
      LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells
      with the activated form of ERBB2 or H-RAS and assessed their metastatic
      potentials by three complementary assays, a wound healing assay, a transwell
      motility assay, and a transwell invasion assay. We showed that while
      overexpression of ERBB2 increased the metastatic potential of the androgen
      insensitive prostate cancer cells (i.e. PC3 and DU145), it did not affect
      metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP
      and Myc-CaP). In contrast, overexpression of H-RAS only increased the cell
      motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data
      suggest that ERBB2 collaborates with androgen signaling to promote prostate
      cancer metastasis, and that although RAS is one of the critical downstream
      effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic
      potentials of prostate cancer cell lines. 

PMID- 24937173
TI  - Prevalence and prognostic significance of Epstein-Barr virus infection in
      classical Hodgkin's lymphoma: a meta-analysis.
AB  - BACKGROUND AND AIMS: The prevalence and prognostic significance of Epstein-Barr
      virus (EBV) infection in classical Hodgkin's lymphomas (cHLs) remain elusive. To
      examine the epidemiological and prognostic differences between EBV-positive and 
      negative cHLs, we conducted a meta-analysis of 119 published studies including
      13,045 cases. METHODS: We pooled the results of relevant published studies
      identified using the PubMed and Embase. The effect sizes of outcome parameters
      were calculated by prevalence, odds ratio (OR), or hazard ratio using a random
      effects model. RESULTS: The pooled prevalence of EBV infection in cHL was 47.9%,
      which was significantly higher in Africa and Central and South America than other
      regions. EBV-positive cHL showed higher incidence in children than in adults
      (69.7 vs. 41.1%). EBV-positive cHL was significantly related to male (OR = 1.8,
      95% CI: 1.510-2.038; p <0.001), mixed cellularity subtype (OR = 3.8, 95% CI:
      3.243-4.451; p <0.001), and advanced clinical stages (OR = 1.2, 95% CI: 1.072
      1.369; p = 0.002). However, the presence of EBV in cHL was not associated with
      overall or event-free survival. CONCLUSIONS: The prevalence of EBV differs
      according to age, sex, region, histologic subtype, and clinical stage of cHL.
      However, the presence of EBV has little effects on cHL patient's survival.

PMID- 24937174
TI  - Reply: Regarding the article: Hepatic ischemia/reperfusion injury is diminished
      by atorvastatin in Wistar rats.

PMID- 24937175
TI  - Regarding the article: Hepatic ischemia/reperfusion injury is diminished by
      atorvastatin in Wistar rats.

PMID- 24937176
TI  - Investigating the binding preferences of small molecule inhibitors of human
      protein arginine methyltransferase 1 using molecular modelling.
AB  - Protein arginine methyltransferases (PRMTs) catalyse the methylation of arginine
      residues of target proteins. PRMTs utilise S-adenosyl methionine (SAM) as the
      methyl group donor, leading to S-adenosyl homocysteine (SAH) and
      monomethylarginine (mMA). A combination of homology modelling, molecular docking,
      Active Site Pressurisation, molecular dynamic simulations and MM-PBSA free energy
      calculations is used to investigate the binding poses of three PRMT1 inhibitors
      (ligands 1-3), which target both SAM and substrate arginine binding sites by
      containing a guanidine group joined by short linkers with the SAM derivative. It
      was assumed initially that the adenine moieties of the inhibitors would bind in
      sub-site 1 (PHE44, GLU137, VAL136 and GLU108), the guanidine side chain would
      occupy sub-site 2 (GLU 161, TYR160, TYR156 and TRP302), with the amino acid side
      chain occupying sub-site 3 (GLU152, ARG62, GLY86 and ASP84; pose 1). However, the
      SAH homocysteine moiety does not fully occupy sub-site 3, suggesting another
      binding pose may exist (pose 2), whereby the adenine moiety binds in sub-site 1,
      the guanidine side chain occupies sub-site 3, and the amino acid side chain
      occupies sub-site 2. Our results indicate that ligand 1 (pose 1 or 2), ligand 2
      (pose 2) and ligand 3 (pose 1) are the predominant binding poses and we
      demonstrate for the first time that sub-site 3 contains a large space that could
      be exploited in the future to develop novel inhibitors with higher binding
      affinities. 

PMID- 24937178
TI  - MicroRNA-155 induction by Mycobacterium bovis BCG enhances ROS production through
      targeting SHIP1.
AB  - Macrophages play a critical role in the host immune response against
      mycobacterial infection. Our previous study has demonstrated that microRNA-155
      (miR-155), one of the most important small non-coding RNAs in the immune system,
      promotes oxygen-independent mycobacterial killing in macrophages. However, little
      is known regarding the role of miR-155 in modulating oxygen-dependent
      mycobactericidal response in macrophages, including the production of reactive
      oxygen species (ROS) and reactive nitrogen species (RNS). In the present study,
      we demonstrated that miR-155 was increased in macrophages after Mycobacterium
      bovis bacille Calmette-Guerin (BCG) infection. Moreover, the BCG-induced
      upregulation of miR-155 in macrophages was dependent on TLR2, NF-kappaB and JNK
      signaling pathways. More importantly, our study explored that miR-155
      significantly elevated ROS production in macrophages, although miR-155 had no
      influence on the inducible nitric oxide synthase (iNOS) expression or nitric
      oxide (NO) production. In addition, our study demonstrated that miR-155 repressed
      the expression of src homology 2 (SH2) containing inositol 5-phosphatase1
      (SHIP1), and knockdown of SHIP1 greatly increased ROS production in BCG-infected
      macrophages. Collectively, these data indicate that miR-155 modulates ROS but not
      RNS production by targeting SHIP1, which may provide a better understanding of
      the host anti-mycobacterial response. 

PMID- 24937177
TI  - Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection
      stages and outcomes.
AB  - RATIONALE: Pseudomonas aeruginosa undergoes phenotypic changes during cystic
      fibrosis (CF) lung infection. Although mucoidy is traditionally associated with
      transition to chronic infection, we hypothesized that additional in vitro
      phenotypes correlate with this transition and contribute to disease. OBJECTIVES:
      To characterize the relationships between in vitro P. aeruginosa phenotypes,
      infection stage, and clinical outcomes. METHODS: A total of 649 children with CF
      and newly identified P. aeruginosa were followed for a median 5.4 years during
      which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro
      bacterial phenotypes were assessed among the isolates, including measures of
      motility, exoproduct production, colony morphology, growth, and metabolism.
      MEASUREMENTS AND MAIN RESULTS: P. aeruginosa phenotypes present at the time of
      culture were associated with both stage of infection (new onset, intermittent, or
      chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation
      (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best
      distinguished infection stages: pyoverdine production (31% of new-onset cultures,
      48% of intermittent, 69% of chronic) and reduced protease production (31%, 39%,
      and 65%, respectively). The best P. aeruginosa phenotypic predictors of
      subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95% confidence
      interval, 1.19-2.57) and reduced twitching motility (odds ratio, 1.43; 95%
      confidence interval, 1.11-1.84). CONCLUSIONS: In this large epidemiologic study
      of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro
      phenotypes that best distinguished early and later infection stages. Among the
      many phenotypes tested, mucoidy and reduced twitching best predicted subsequent
      PE. These phenotypes indicate potentially useful prognostic markers of transition
      to chronic infection and advancing lung disease.

PMID- 24937179
TI  - Eosinophil peroxidase induces expression of cholinergic genes via cell surface
      neural interactions.
AB  - Eosinophils localize to and release their granule proteins in close association
      with nerves in patients with asthma and rhinitis. These conditions are associated
      with increased neural function. In this study the effect of the individual
      granule proteins on cholinergic neurotransmitter expression was investigated.
      Eosinophil peroxidase (EPO) upregulated choline acetyltransferase (ChAT) and
      vesicular acetylcholine transporter (VAChT) gene expression. Fluorescently
      labeled EPO was seen to bind to the IMR-32 cell surface. Both Poly-L-Glutamate
      (PLG) and Heparinase-1 reversed the up-regulatory effect of EPO on ChAT and VAChT
      expression and prevented EPO adhesion to the cell surface. Poly-L-arginine (PLA)
      had no effect on expression of either gene, suggesting that charge is necessary
      but insufficient to alter gene expression. EPO induced its effects via the
      activation of NF-kappaB. MEK inhibition led to reversal of all up-regulatory
      effects of EPO. These data indicate a preferential role of EPO signaling via a
      specific surface receptor that leads to neural plasticity.

PMID- 24937181
TI  - Detection of amines with extended distyrylbenzenes by strip assays.
AB  - We herein describe the synthesis and property evaluation of three novel aldehyde
      substituted pentameric phenylenevinylenes carrying branched oligo(ethylene
      glycol) (swallowtail, Sw) substituents. The targets were synthesized by a
      combination of Heck coupling and Wittig or Horner reactions of suitable precursor
      modules. If the pentameric phenylenevinylene carries only two of these Sw
      substituents, it is no longer water-soluble. When six of the Sw substituents are
      attached, regardless of their position, the pentameric phenylenevinylenes are
      well water-soluble. The dialdehydes were investigated with respect to their amine
      sensing capabilities both in water as well as in the solid state, sprayed onto
      thin layer chromatography (TLC) plates (alox, silica gel, reversed phase silica
      gel). The recognition of amine vapors using the sprayed-on phenylenevinylene
      dialdehydes is superb and allows the identification of different amines on
      regular silica TLC plates via color changes, analyzed by a statistical tool, the
      multivariate analysis of variance (MANOVA) protocol. 

PMID- 24937180
TI  - Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST
      guideline and expert panel report.
AB  - OBJECTIVE: Choices of pharmacologic therapies for pulmonary arterial hypertension
      (PAH) are ideally guided by high-level evidence. The objective of this guideline
      is to provide clinicians advice regarding pharmacologic therapy for adult
      patients with PAH as informed by available evidence. METHODS: This guideline was
      based on systematic reviews of English language evidence published between 1990
      and November 2013, identified using the MEDLINE and Cochrane Library databases.
      The strength of available evidence was graded using the Grades of
      Recommendations, Assessment, Development, and Evaluation methodology. Guideline
      recommendations, or consensus statements when available evidence was insufficient
      to support recommendations, were developed using a modified Delphi technique to
      achieve consensus. RESULTS: Available evidence is limited in its ability to
      support high-level recommendations. Therefore, we drafted consensus statements to
      address many clinical questions regarding pharmacotherapy for patients with PAH.
      A total of 79 recommendations or consensus statements were adopted and graded.
      CONCLUSIONS: Clinical decisions regarding pharmacotherapy for PAH should be
      guided by high-level recommendations when sufficient evidence is available.
      Absent higher level evidence, consensus statements based upon available
      information must be used. Further studies are needed to address the gaps in
      available knowledge regarding optimal pharmacotherapy for PAH.

PMID- 24937183
TI  - Synthesis and cytotoxic effect on cancer cell lines and macrophages of novel
      progesterone derivatives having an ester or a carbamate function at C-3 and C-17.
AB  - In this study we report the cytotoxic effect on human cancer cells of two series
      of novel progesterone derivatives; the first containing an aromatic ester (8a-e)
      or a carbamate functions both linked to C-3 (9a-e) on the pregn-4,16-diene-6,20
      dione skeleton. In the second series, both functional groups (ester and
      carbamate) are bound to C-17 on the pregn-4,6-diene-3,20-dione scaffold (13a-e
      and 14a-e). The panel cancer cell lines used in this study were the following: PC
      3 (human prostate cancer cell line), MCF-7 (human breast cancer cell line), HCT
      15 (human colon cancer cell line) and J774 (noncancerous murine macrophages) for
      comparison. The results from this study showed that steroid 14a, having a
      carbamate function at C-17, was the most potent against PC-3 cell line (96.6%)
      while 8c and 8e showed much higher cytotoxic activity (100%) for MCF-7 cell line.
      Finally, compounds 8c and 14a displayed selective properties towards tumor cell
      lines than noncancerous murine macrophages. 

PMID- 24937184
TI  - Design, synthesis and structure-activity relationship of novel semi-synthetic
      flavonoids as antiproliferative agents.
AB  - Various flavonoid scaffold based derivatives viz furochalcones (3a-e, 6a-d and 9a
      d), furoflavones (10a-d, 11a-d, 12a-d, 18a&b), flavones (21a-d), furoaurones
      (13a,b, 14a-d and 15a-d) and 7-styrylfurochromones (22a-d and 25a-e) were
      designed and synthesized. The novel compounds were evaluated for their
      antiproliferative activity against a panel of 60 cancer cell lines comprising 9
      types of tumors. Ten compounds belonging to the major subgroups of flavonoids viz
      furochalcones (3a, 3d, 6b, 9a and 9b), furoflavones (12a and 12c), furoaurones
      (15d), styrylfurochromones (25b and 25e) showed very promising activity. These
      active compounds were also evaluated in vitro as kinase inhibitors against
      CDK2/cyclin E1, CDK4/cyclin D1 and GSK-3beta and the best inhibition was
      displayed against GSK-3beta with the allylfurochalcone derivative 9b exhibiting
      80% decrease in GSK-3beta catalytic activity. On the other hand, the
      styrylfurochromone 25e interestingly showed a 13% enhancement of GSK-3beta
      catalytic power and a 12% reduction in CDK4/cyclin D1 activity. Finally, the in
      vivo anti-tumor activity of 25e was evaluated against breast cancer induced in
      mice. The results showed a profound anti-tumor effect of 25e that accompanies a
      significant increase and decrease in the levels of GSK-3beta and cyclin D1,
      respectively.

PMID- 24937185
TI  - Development of second generation EP2 antagonists with high selectivity.
AB  - EP2 receptor has emerged as an important biological target for therapeutic
      intervention. In particular, it has been shown to exacerbate disease progression
      of a variety of CNS and peripheral diseases. Deletion of the EP2 receptor in
      mouse models recapitulates several features of the COX-2 inhibition, thus
      presenting a new avenue for anti-inflammatory therapy which could bypass some of
      the adverse side effects observed by the COX-2 inhibition therapy. We have
      recently reported a cinnamic amide class of EP2 antagonists with high potency,
      but these compounds exhibited a moderate selectivity against prostanoid receptor
      DP1. Moreover they possess acrylamide moiety in the structure, which may result
      in liver toxicity over longer period of use in a chronic disease model. Thus, we
      now developed a second generation compounds that devoid of the acrylamide
      functionality and possess high potency and improved (>1000-fold) selectivity to
      EP2 over other prostanoid receptors. 

PMID- 24937186
TI  - Design, synthesis and biological activity of piperlongumine derivatives as
      selective anticancer agents.
AB  - In an effort to expand the structure-activity relationship of the natural
      anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine
      derivatives with halogen or morpholine substituents at C2 and alkyl substituents
      at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity
      against four cancer cells and modest selectivity for lung normal cells. The
      highly active anticancer compound 11h exhibited obvious ROS elevation and
      excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the
      dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic
      group at C2 played an important role in increasing cytotoxicity.

PMID- 24937187
TI  - Change deafness and object encoding with recognizable and unrecognizable sounds.
AB  - Change deafness is the failure to notice changes in an auditory scene. In this
      study, we sought to determine if change deafness is a perceptual error, rather
      than only a reflection of verbal memory limitations. We also examined how
      successful encoding of objects within a scene is related to successful detection
      of changes. Event-related potentials (ERPs) were recorded while listeners
      completed a change-detection and an object-encoding task with scenes composed of
      recognizable sounds or unrecognizable temporally scrambled versions of the
      recognizable sounds. More change deafness occurred for the unrecognizable,
      compared to recognizable sounds, indicating that change deafness is a perceptual
      error and not solely a product of verbal memory. ERPs from both the recognizable
      and unrecognizable scenes revealed an enhanced P3b (at PZ/1/2, POZ/3/4 from 350
      to 750ms) to detected changes, a marker that conscious change detection has
      occurred. Recognizable scenes resulted in an enhanced T400 (at T8/TP8, C6/CP6
      from 315 to 660ms) to detected changes, possibly indicating activation of
      established memory representations. Unrecognizable scenes elicited an enhanced
      P3a (at FCZ/1/2 from 280 to 600ms) to detected changes, indicating enhanced
      orienting to acoustic change. Performance on the object-encoding task revealed
      that change deafness was reduced, but not eliminated, when performance on the
      object-encoding task was accurate.

PMID- 24937182
TI  - 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer
      patients treated with chemotherapy.
AB  - Large population-based registry studies have shown that breast cancer prognosis
      is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes
      implicated in human immunology and inflammation as candidates for prognostic
      markers of breast cancer survival involving 1,804 oestrogen receptor (ER)
      negative patients treated with chemotherapy (279 events) from 14 European studies
      in a prior large-scale genotyping experiment, which is part of the Collaborative
      Oncological Gene-environment Study (COGS) initiative. We carry out replication
      using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes
      in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events).
      Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer
      specific death at a genome-wide significant level (n=2,641, 440 events, combined
      allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 * 10(-9)). Such
      survival-associated variants can represent ideal targets for tailored
      therapeutics, and may also enhance our current prognostic prediction
      capabilities. 

PMID- 24937189
TI  - Heparanase is a key player in renal fibrosis by regulating TGF-beta expression
      and activity.
AB  - Epithelial-mesenchymal transition (EMT) of tubular cells is one of the mechanisms
      which contribute to renal fibrosis and transforming growth factor-beta (TGF-beta)
      is one of the main triggers. Heparanase (HPSE) is an endo-beta-D-glucuronidase
      that cleaves heparan-sulfate thus regulating the bioavailability of growth
      factors (FGF-2, TGF-beta). HPSE controls FGF-2-induced EMT in tubular cells and
      is necessary for the development of diabetic nephropathy in mice. The aim of this
      study was to investigate whether HPSE can modulate the expression and the effects
      of TGF-beta in tubular cells. First we proved that the lack of HPSE or its
      inhibition prevents the increased synthesis of TGF-beta by tubular cells in
      response to pro-fibrotic stimuli such as FGF-2, advanced glycosylation end
      products (AGE) and albumin overload. Second, since TGF-beta may derive from
      sources different from tubular cells, we investigated whether HPSE modulates
      tubular cell response to exogenous TGF-beta. HPSE does not prevent EMT induced by
      TGF-beta although it slows its onset; indeed in HPSE-silenced cells the
      acquisition of a mesenchymal phenotype does not develop as quickly as in wt
      cells. Additionally, TGF-beta induces an autocrine loop to sustain its signal,
      whereas the lack of HPSE partially interferes with this autocrine loop. Overall
      these data confirm that HPSE is a key player in renal fibrosis since it interacts
      with the regulation and the effects of TGF-beta. HPSE is needed for pathological
      TGF-beta overexpression in response to pro-fibrotic factors. Furthermore, HPSE
      modulates TGF-beta-induced EMT: the lack of HPSE delays tubular cell
      transdifferentiation, and impairs the TGF-beta autocrine loop. 

PMID- 24937190
TI  - miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and
      differentiation.
AB  - Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC)
      differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs)
      are small RNA molecules of 21-25 nucleotides that regulate many aspects of
      osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling in hMSC.
      We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt
      signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells
      at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast
      differentiation of hMSC as evidenced by reduced alkaline phosphatase activity,
      gene expression and in vitro mineralized matrix formation. Bioinformatic studies,
      Western blot analysis and 3'UTR reporter assay demonstrated that cell division
      cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of
      CDC25A inhibited hMSC proliferation and osteoblast differentiation. In summary,
      miR-141-3p acts as a negative regulator of hMSC proliferation and osteoblast
      differentiation. Targeting miR-141-3p could be used as an anabolic therapy of low
      bone mass diseases, e.g. osteoporosis. 

PMID- 24937191
TI  - When the Patient Is Sicker Than His Liver.

PMID- 24937188
TI  - Beyond the FFA: The role of the ventral anterior temporal lobes in face
      processing.
AB  - Extensive research has supported the existence of a specialized face-processing
      network that is distinct from the visual processing areas used for general object
      recognition. The majority of this work has been aimed at characterizing the
      response properties of the fusiform face area (FFA) and the occipital face area
      (OFA), which together are thought to constitute the core network of brain areas
      responsible for facial identification. Although accruing evidence has shown that
      face-selective patches in the ventral anterior temporal lobes (vATLs) are
      interconnected with the FFA and OFA, and that they play a role in facial
      identification, the relative contribution of these brain areas to the core face
      processing network has remained unarticulated. Here we review recent research
      critically implicating the vATLs in face perception and memory. We propose that
      current models of face processing should be revised such that the ventral
      anterior temporal lobes serve a centralized role in the visual face-processing
      network. We speculate that a hierarchically organized system of face processing
      areas extends bilaterally from the inferior occipital gyri to the vATLs, with
      facial representations becoming increasingly complex and abstracted from low
      level perceptual features as they move forward along this network. The anterior
      temporal face areas may serve as the apex of this hierarchy, instantiating the
      final stages of face recognition. We further argue that the anterior temporal
      face areas are ideally suited to serve as an interface between face perception
      and face memory, linking perceptual representations of individual identity with
      person-specific semantic knowledge. 

PMID- 24937192
TI  - Coronary plaque burden, as determined by cardiac computed tomography, in patients
      with myocardial infarction and angiographically normal coronary arteries compared
      to healthy volunteers: a prospective multicenter observational study.
AB  - OBJECTIVES: Patients presenting with acute myocardial infarction and
      angiographically normal coronary arteries (MINCA) represent a diagnostic and a
      therapeutic challenge. Cardiac computed tomography (CT) allows detection of
      coronary artery disease (CAD) even in the absence of significant stenosis. We
      aimed to investigate whether patients suffering from MINCA had a greater coronary
      plaque burden, as determined by cardiac CT, than a matched group of healthy
      volunteers. METHODS: Consecutive patients, aged 45 to 70, with MINCA were
      enrolled in the Stockholm metropolitan area. Patients with myocarditis were
      excluded using cardiovascular magnetic resonance imaging. Remaining patients
      underwent cardiac CT, as did a reference group of healthy volunteers matched by
      age and gender, with no known cardiovascular disease. Plaque burden was evaluated
      semi-quantitatively on a per patient and a per segment level. RESULTS: Despite a
      higher prevalence of smoking and hypertension, patients with MINCA did not have
      more CAD than healthy volunteers. Among 57 MINCA patients and 58 volunteers no
      signs of CAD were found in 24 (42%) and 25 (43%) respectively. On a per segment
      level, MINCA patients had less segments with stenosis >= 20% (2% vs. 5%, p<0.01),
      as well as a smaller proportion of large (2% vs. 4%, p<0.05) and mixed type
      plaques (1% vs. 4%, p<0.01). The median coronary calcium score did not differ
      between MINCA patients and healthy volunteers (6 vs. 8, ns). CONCLUSIONS: MINCA
      patients with no or minimal angiographic stenosis do not have more coronary
      atherosclerosis than healthy volunteers, and a large proportion of these patients
      do not have any signs of CAD, as determined by cardiac CT. The MINCA patient
      group is probably heterogeneous, with a variety of different underlying
      mechanisms. Non-obstructive CAD is most likely not the most prevalent cause of
      myocardial infarction in this patient group.

PMID- 24937194
TI  - Vibrational frequencies of fullerenes C60 and C70 under pressure studied with a
      quantum chemical model including spatial confinement effects.
AB  - The equilibrium geometry structural and vibrational spectroscopic properties of
      fullerenes C60 and C70 under high pressure have been studied with a quantum
      chemical computational approach in which ab initio calculations on a single
      fullerene molecule have been carried out within the polarizable continuum model
      framework to mimic pressure effects. The adopted approach has been revealed
      effective to explain the geometry variations and the frequency shifts observed
      experimentally. 

PMID- 24937193
TI  - Medical and regenerative solutions for congenital diaphragmatic hernia: a
      perinatal perspective.
AB  - In the EU-27, 2,100 babies with congenital diaphragmatic hernia (CDH) are born
      annually. CDH is fatal in 30% of them. Experimental fetal surgery in severe cases
      results in a survival rate of 50 to 60% at its best. Failure is due to
      insufficient lung growth, persistent pulmonary hypertension or prematurity
      induced by the procedure. For nonsurvivors alternative strategies are required.
      Survivors undergo anatomical repair, but large diaphragmatic defects are closed
      using a patch. At present the used materials are less than ideal, mainly because
      of recurrence and chest deformation. To overcome the above limitations,
      alternative medical therapies (pharmacologic or cell therapy) that are more
      potent and less invasive are needed. Also a more functional postnatal repair may
      be possible when using novel scaffolds or engineered constructs. We see a
      prominent place for autologous amniotic fluid-derived stem cells for these novel
      strategies, which could be prenatally harvested following appropriate patient
      selection by noninvasive imaging. 

PMID- 24937196
TI  - Designing hollow nano gold golf balls.
AB  - Hollow/porous nanoparticles, including nanocarriers, nanoshells, and mesoporous
      materials have applications in catalysis, photonics, biosensing, and delivery of
      theranostic agents. Using a hierarchical template synthesis scheme, we have
      synthesized a nanocarrier mimicking a golf ball, consisting of (i) solid silica
      core with a pitted gold surface and (ii) a hollow/porous gold shell without
      silica. The template consisted of 100 nm polystyrene beads attached to a larger
      silica core. Selective gold plating of the core followed by removal of the
      polystyrene beads produced a golf ball-like nanostructure with 100 nm pits.
      Dissolution of the silica core produced a hollow/porous golf ball-like
      nanostructure. 

PMID- 24937195
TI  - Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in
      vivo.
AB  - Bioactive supramolecular nanostructures are of great importance in regenerative
      medicine and the development of novel targeted therapies. In order to use
      supramolecular chemistry to design such nanostructures, it is extremely important
      to track their fate in vivo through the use of molecular imaging strategies.
      Peptide amphiphiles (PAs) are known to generate a wide array of supramolecular
      nanostructures, and there is extensive literature on their use in areas such as
      tissue regeneration and therapies for disease. We report here on a series of PA
      molecules based on the well-established beta-sheet amino acid sequence V3A3
      conjugated to macrocyclic Gd(III) labels for magnetic resonance imaging (MRI).
      These conjugates were shown to form cylindrical supramolecular assemblies using
      cryogenic transmission electron microscopy and small-angle X-ray scattering.
      Using nuclear magnetic relaxation dispersion analysis, we observed that thermal
      annealing of the nanostructures led to a decrease in water exchange lifetime
      (taum) of hundreds of nanoseconds only for molecules that self-assemble into
      nanofibers of high aspect ratio. We interpret this decrease to indicate more
      solvent exposure to the paramagnetic moiety on annealing, resulting in faster
      water exchange within angstroms of the macrocycle. We hypothesize that faster
      water exchange in the nanofiber-forming PAs arises from the dehydration and
      increase in packing density on annealing. Two of the self-assembling conjugates
      were selected for imaging PAs after intramuscular injections of the PA C16V3A3E3
      NH2 in the tibialis anterior muscle of a murine model. Needle tracts were clearly
      discernible with MRI at 4 days postinjection. This work establishes Gd(III)
      macrocycle-conjugated peptide amphiphiles as effective tracking agents for
      peptide amphiphile materials in vivo over the timescale of days. 

PMID- 24937197
TI  - Low-temperature solution-processed flexible solar cells based on (In,Ga)N
      nanocubes.
AB  - Indium gallium nitride nanocubes were syntheized via a low-temperature chemical
      route. Energy-dispersive X-ray spectroscopy and X-ray diffraction analyses
      confirmed the successful fabrication of (In,Ga)N with various indium mole
      fractions. The bandgap of the material was tunded as a function of the indium
      content. The fabricated nanocubes showed a deep level photoluminescence emission
      at 734 nm as well as in the visible region at 435-520 nm. The Hall effect
      measurements showed the hole concentration to constantly increase from 6.2 *
      10(16) to 2.3 * 10(18) cm(-3), while the hole mobility to decrease from 0.92 to
      0.1 cm(2) /(V s) as the doping ratio increases from 0.005 to 0.025 cm(-3). The
      solar cell device made of nanocubes film containing 0.4 indium on flexible
      substrates showed a short-circuit current density of 12.47 mA/cm(2) and an open
      circuit voltage (Voc) of 0.48 V with 54% fill factor. The relationship between
      Voc and indium content in the fabricated films was also investigated. 

PMID- 24937198
TI  - Late antibody-mediated rejection in renal allografts: outcome after conventional
      and novel therapies.
AB  - BACKGROUND: Although several strategies for treating early antibody-mediated
      rejection (AMR) in kidney transplants have been investigated, evidence on
      treatment of late AMR manifesting after 6 months is sparse. In this single-center
      series, we present data on 23 consecutive patients treated for late AMR. METHODS:
      Late AMR was diagnosed using Banff 2007 criteria along with presence of donor
      specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to
      therapy was assessed by improvement in SCr, histologic improvement, and decline
      in DSA strength. RESULTS: Overall, 17% (4/23) had documented nonadherence while
      69% (16/23) had physician-recommended reduction in immunosuppression before AMR.
      Eighteen patients (78%) were treated with plasmapheresis or low-dose
      IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of
      bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at
      the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this
      improvement was not sustained at most recent follow-up. Eleven (48%) patients had
      no histologic resolution on follow-up biopsy. Lack of histologic response was
      associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of
      cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic
      vasculopathy (cv>=2) on index biopsy (OR=50; P=0.06). CONCLUSIONS: A major
      setting in which late AMR occurred in our cohort was reduction or change in
      immunosuppression. Our data demonstrate an inadequate response of late AMR to
      current and novel (bortezomib) therapies. The benefits of therapy need to be
      counterweighed with potential adverse effects especially in older patients, large
      antibody loads, and chronic allograft vasculopathy.

PMID- 24937199
TI  - High dose intravenous immunoglobulin therapy for donor-specific antibodies in
      kidney transplant recipients with acute and chronic graft dysfunction.
AB  - BACKGROUND: Postkidney transplant donor-specific antibodies (DSA) have been
      identified as important contributors to graft loss. Few therapeutic options exist
      and have been met with limited success. We report outcomes in patients with de
      novo DSA and graft damage treated with a protocol of high-dose intravenous
      immunoglobulin (IVIG). METHODS: Retrospective analysis of 28 kidney transplant
      recipients with de novo DSA and graft damage in the form of either chronic graft
      dysfunction (group 1, n=20) or a recent previous acute antibody-mediated
      rejection (AMR) episode (group 2, n=8) prescribed a standard regimen of high-dose
      (5 g/kg) IVIG dosed over 6 months. RESULTS: Mean fluorescence intensity (MFI) of
      70 total DSA decreased by 12%at the end of treatment (T1, P=0.14) and by 18%at
      last follow up (T2, P=0.035) compared with treatment initiation (T0) MFI. The
      most robust effect was seen in class I DSA (37% decrease at T2 versus T0, P=0.05)
      and in DSA from patients in group 2 (52% decrease at T2 versus T0, P=0.008).
      Graft function stabilized in patients in group 2 but continued to decline in
      those in group 1. CONCLUSION: High-dose IVIG resulted in modest DSA MFI
      reductions in patients with previous graft damage, with a larger effect occurring
      in class I DSA in patients with a previous acute AMR. There was no clinical
      treatment benefit in patients with ongoing chronic graft damage, whereas high
      dose IVIG may reduce the risk of chronic graft dysfunction in those with an acute
      AMR event.

PMID- 24937200
TI  - The contribution of DNA metabarcoding to fungal conservation: diversity
      assessment, habitat partitioning and mapping red-listed fungi in protected
      coastal Salix repens communities in the Netherlands.
AB  - Western European coastal sand dunes are highly important for nature conservation.
      Communities of the creeping willow (Salix repens) represent one of the most
      characteristic and diverse vegetation types in the dunes. We report here the
      results of the first kingdom-wide fungal diversity assessment in S. repens
      coastal dune vegetation. We carried out massively parallel pyrosequencing of ITS
      rDNA from soil samples taken at ten sites in an extended area of joined nature
      reserves located along the North Sea coast of the Netherlands, representing
      habitats with varying soil pH and moisture levels. Fungal communities in Salix
      repens beds are highly diverse and we detected 1211 non-singleton fungal 97%
      sequence similarity OTUs after analyzing 688,434 ITS2 rDNA sequences. Our
      comparison along a north-south transect indicated strong correlation between soil
      pH and fungal community composition. The total fungal richness and the number
      OTUs of most fungal taxonomic groups negatively correlated with higher soil pH,
      with some exceptions. With regard to ecological groups, dark-septate endophytic
      fungi were more diverse in acidic soils, ectomycorrhizal fungi were represented
      by more OTUs in calcareous sites, while detected arbuscular mycorrhizal genera
      fungi showed opposing trends regarding pH. Furthermore, we detected numerous red
      listed species in our samples often from previously unknown locations, indicating
      that some of the fungal species currently considered rare may be more abundant in
      Dutch S. repens communities than previously thought. 

PMID- 24937201
TI  - Comparative analysis of the quality of life for patients prior to and after heart
      transplantation.
AB  - BACKGROUND: The aim of this study was to assess the quality of life of patients
      before and after heart transplantation (HTX). MATERIAL AND METHODS: We included
      63 patients after a heart transplant under the care of the Transplantation
      Clinic. The authors' questionnaire was used, which consisted of 2 parts:
      questions concerning the life of patients before and after a heart transplant.
      The significance level was p<0.05. RESULTS: In the group before the heart
      transplant, average quality of life (on a 10-point scale) was 3.16 +/- 1.47 and
      in the group after the heart transplant this factor increased to 7.60 +/- 1.21
      (p<0.00001). Our study shows that after the heart transplant people consider
      their physical health to be better. In the group before the heart transplant, the
      average assessment of physical health on a scale from 1 to 5 was 2.079 +/- 0.79
      and after the heart transplant it was 4.10 +/- 0.39 (p<0.0001). No statistically
      significant correlations were indicated between the quality of life after the
      heart transplant and the quality of life before the transplant, age, sex, and
      time elapsed after the heart transplant. There was a positive correlation between
      the assessment of quality of life and that of physical (r=0.53; p<0.05) and
      mental health (r=0.45; p<0.05). CONCLUSIONS: The study shows that the quality of
      life of patients after the heart transplant was significantly improved in all
      spheres of life under analysis: physical, mental, social, and family. The results
      of the study indicate that patients associated the quality of life with their
      physical and mental health status.

PMID- 24937202
TI  - Evidence for global cooling in the Late Cretaceous.
AB  - The Late Cretaceous 'greenhouse' world witnessed a transition from one of the
      warmest climates of the past 140 million years to cooler conditions, yet still
      without significant continental ice. Low-latitude sea surface temperature (SST)
      records are a vital piece of evidence required to unravel the cause of Late
      Cretaceous cooling, but high-quality data remain illusive. Here, using an organic
      geochemical palaeothermometer (TEX86), we present a record of SSTs for the
      Campanian-Maastrichtian interval (~83-66 Ma) from hemipelagic sediments deposited
      on the western North Atlantic shelf. Our record reveals that the North Atlantic
      at 35  degrees N was relatively warm in the earliest Campanian, with maximum SSTs
      of ~35  degrees C, but experienced significant cooling (~7  degrees C) after this
      to <~28  degrees C during the Maastrichtian. The overall stratigraphic trend is
      remarkably similar to records of high-latitude SSTs and bottom-water
      temperatures, suggesting that the cooling pattern was global rather than regional
      and, therefore, driven predominantly by declining atmospheric pCO2 levels. 

PMID- 24937203
TI  - Rhodium(III)-catalyzed regioselective C2-amidation of indoles with N-(2,4,6
      trichlorobenzoyloxy)amides and its synthetic application to the development of a
      novel potential PPARgamma modulator.
AB  - A new and efficient method for the direct regioselective C2-amidation of various
      functionalized indoles with several N-(2,4,6-trichlorobenzoyloxy)amides via
      Rh(iii)-catalyzed C-H activation/N-O cleavage/C-N formation using the pyrimidyl
      group as a readily installable and removable directing group has been developed.
      With this method, a variety of valuable 2-amido indoles can be easily prepared
      under mild conditions with broad functional group tolerance and excellent region
      /site-specificities. Application of this strategy to the synthesis of target
      compound as a novel PPARgamma modulator was also demonstrated. The results from
      biological evaluation showed that compound had a partial PPARgamma agonistic
      activity and a strong PPARgamma binding affinity with an IC50 value of 120.0 nM,
      along with a less pronounced adipocyte differentiation ability compared to the
      currently marketed anti-diabetic drug rosiglitazone, suggesting that further
      development of such a compound might be of great interest. 

PMID- 24937204
TI  - Central nervous system penetration and effectiveness of darunavir/ritonavir
      monotherapy.
AB  - Darunavir/ritonavir monotherapy is an experimental switching strategy for
      virologically suppressed patients without protease inhibitor resistance to avoid
      nucleos(t)ide-related toxicities. This therapy maintains virological suppression
      in most patients, but at slightly lower rates than standard therapy that includes
      two nucleos(t)ides. Patients experiencing virological failure are generally re
      suppressed without emergence of resistance with the resumption of two
      nucleos(t)ides. Reports of cerebrospinal fluid viral escape has been observed in
      patients receiving protease inhibitor monotherapy, and concerns exist regarding
      the capacity of protease inhibitor monotherapy to control HIV infection in the
      brain and to prevent neurocognitive decline. In the current report we have pooled
      together available evidence regarding the capacity of darunavir/ritonavir
      monotherapy to control HIV replication in cerebrospinal fluid and to prevent
      neurocognitive decline. 

PMID- 24937205
TI  - Cycling time trial performance may be impaired by whey protein and L-alanine
      intake during prolonged exercise.
AB  - Previous studies reported that adding protein (PRO) to carbohydrate (CHO)
      solutions enhances endurance performance. The ergogenic effect may be a function
      of additional protein/amino acid calories, but this has not been examined. In
      addition, although supplemental L-alanine (ALA) is readily oxidized during
      exercise, the subsequent impact on metabolism and prolonged endurance performance
      is unknown. The purpose of this investigation was to independently gauge the
      impact of whey PRO hydrolysate and ALA supplementation on performance and various
      physiological parameters. Eight cyclists (age: 22.3 +/- 5.6 yr, weight: 70.0 +/-
      8.0 kg, VO2max: 59.4 +/- 4.9 ml . kg(-1) . min(-1)) performed 120 min of constant
      load cycling (55% of peak power) followed by a 30-km time trial (TT) under
      placebo (PLA), PRO, and ALA conditions. Magnitude-based qualitative inferences
      were applied to evaluate treatment differences and data are presented as percent
      difference between treatments +/- 90% confidence limit. Both ALA (2.1 +/- 2.7%)
      and PRO intake (-2.1 +/- 2.2%) possibly harmed performance compared with PLA. Of
      interest, heart rate was possibly lower with ALA than PLA at 20- (-2.7 +/- 3.4%)
      and 120-min (-1.7 +/- 2.9%) of constant-load cycling and the serum interleukin-6
      (IL-6) response to 120 min of cycling was likely attenuated with PRO compared
      with PLA (PLA, 6.6 +/- 3.7 fold vs. PRO, 2.9 +/- 1.8 fold). In addition, blood
      glucose levels were lower with PRO than PLA at 20- (-8.8 +/- 2.3%; very likely)
      and 120-min (-4.9 +/- 4.6%; likely) of constant-load cycling. Although ALA intake
      appears to lower HR and PRO ingestion dampens the IL-6 response to exercise, the
      ingestion of PRO (without CHO) or ALA does not enhance, and may actually impair,
      performance following prolonged cycling.

PMID- 24937206
TI  - Recent advances toward a general purpose linear-scaling quantum force field.
AB  - Conspectus There is need in the molecular simulation community to develop new
      quantum mechanical (QM) methods that can be routinely applied to the simulation
      of large molecular systems in complex, heterogeneous condensed phase
      environments. Although conventional methods, such as the hybrid quantum
      mechanical/molecular mechanical (QM/MM) method, are adequate for many problems,
      there remain other applications that demand a fully quantum mechanical approach.
      QM methods are generally required in applications that involve changes in
      electronic structure, such as when chemical bond formation or cleavage occurs,
      when molecules respond to one another through polarization or charge transfer, or
      when matter interacts with electromagnetic fields. A full QM treatment, rather
      than QM/MM, is necessary when these features present themselves over a wide
      spatial range that, in some cases, may span the entire system. Specific examples
      include the study of catalytic events that involve delocalized changes in
      chemical bonds, charge transfer, or extensive polarization of the macromolecular
      environment; drug discovery applications, where the wide range of nonstandard
      residues and protonation states are challenging to model with purely empirical MM
      force fields; and the interpretation of spectroscopic observables. Unfortunately,
      the enormous computational cost of conventional QM methods limit their practical
      application to small systems. Linear-scaling electronic structure methods (LSQMs)
      make possible the calculation of large systems but are still too computationally
      intensive to be applied with the degree of configurational sampling often
      required to make meaningful comparison with experiment. In this work, we present
      advances in the development of a quantum mechanical force field (QMFF) suitable
      for application to biological macromolecules and condensed phase simulations.
      QMFFs leverage the benefits provided by the LSQM and QM/MM approaches to produce
      a fully QM method that is able to simultaneously achieve very high accuracy and
      efficiency. The efficiency of the QMFF is made possible by partitioning the
      system into fragments and self-consistently solving for the fragment-localized
      molecular orbitals in the presence of the other fragment's electron densities.
      Unlike a LSQM, the QMFF introduces empirical parameters that are tuned to obtain
      very accurate intermolecular forces. The speed and accuracy of our QMFF is
      demonstrated through a series of examples ranging from small molecule clusters to
      condensed phase simulation, and applications to drug docking and protein-protein
      interactions. In these examples, comparisons are made to conventional molecular
      mechanical models, semiempirical methods, ab initio Hamiltonians, and a hybrid
      QM/MM method. The comparisons demonstrate the superior accuracy of our QMFF
      relative to the other models; nonetheless, we stress that the overarching role of
      QMFFs is not to supplant these established computational methods for problems
      where their use is appropriate. The role of QMFFs within the toolbox of
      multiscale modeling methods is to extend the range of applications to include
      problems that demand a fully quantum mechanical treatment of a large system with
      extensive configurational sampling. 

PMID- 24937207
TI  - Short-term effects of different genetically modified maize varieties on arthropod
      food web properties: an experimental field assessment.
AB  - There is concern that genetically modified (GM) plants may have adverse affects
      on the arthropod biodiversity comprising agricultural landscapes. The present
      study report on a two year field experimental test of whether four different
      genotypic lines, some are novel with no previous field tests, of GM maize hybrids
      alter the structure of arthropod food webs that they harbour, relative to non-GM
      maize (control) that is widely used in agriculture. The different GM genotypes
      produced either Bt toxins, conferred glyphosate tolerance or a combination of the
      two traits. Quantitative food web analysis, based on short-term assessment
      assigning a total of 243,896 arthropod individuals collected from the treatments
      to their positions in food webs, revealed that complex and stable food webs
      persisted in each maize treatment. Moreover, food web structure remained
      relatively unchanged by the GM-genotype. The results suggest that at least in
      short-term period these particular GM maize genotypes will not have adverse
      effects on arthropod biota of agricultural landscapes. 

PMID- 24937208
TI  - Carex diaoluoshanica (Carex sect. Lageniformes, Cyperaceae), a new species from
      Hainan, China.
AB  - Carex diaoluoshanica, a new species of Carex sect. Lageniformes from Hainan,
      China, is described and illustrated. The new species is similar to C. breviscapa
      but differs in having wider leaves with the leaf base gradually narrowed, 5-10 cm
      long and petiolelike, culms subfiliform, with only two spikes, the lateral female
      spikes from near the culm base. 

PMID- 24937212
TI  - Intermolecular zirconium-catalyzed hydrophosphination of alkenes and dienes with
      primary phosphines.
AB  - Catalytic hydrophosphination of terminal alkenes and dienes with primary
      phosphines (RPH2; R = Cy, Ph) under mild conditions has been demonstrated using a
      zirconium complex, [kappa(5)-N,N,N,N,C-(Me3SiNCH2CH2)2NCH2CH2NSiMe2CH]Zr (1).
      Exclusively anti-Markovnikov functionalized products were observed, and the
      catalysis is selective for either the secondary or tertiary phosphine (i.e.,
      double hydrophosphination) products, depending on reaction conditions. The
      utility of the secondary phosphine products as substrates for further elaboration
      was demonstrated with a platinum-catalyzed asymmetric alkylation reaction. 

PMID- 24937209
TI  - Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei.
AB  - Two new (1 and 2) and four known arylnaphthalene lignan lactones (3-6) were
      isolated from different plant parts of Phyllanthus poilanei collected in Vietnam,
      with two further known analogues (7 and 8) being prepared from phyllanthusmin C
      (4). The structures of the new compounds were determined by interpretation of
      their spectroscopic data and by chemical methods, and the structure of
      phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis.
      Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29
      human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-alpha-L
      arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50
      values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in
      an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr
      nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic
      effects by inducing tumor cell apoptosis through activation of caspase-3, but it
      did not inhibit DNA topoisomerase IIalpha activity.

PMID- 24937211
TI  - Drift rather than selection dominates MHC class II allelic diversity patterns at
      the biogeographical range scale in natterjack toads Bufo calamita.
AB  - Study of major histocompatibility complex (MHC) loci has gained great popularity
      in recent years, partly due to their function in protecting vertebrates from
      infections. This is of particular interest in amphibians on account of major
      threats many species face from emergent diseases such as chytridiomycosis. In
      this study we compare levels of diversity in an expressed MHC class II locus with
      neutral genetic diversity at microsatellite loci in natterjack toad (Bufo
      (Epidalea) calamita) populations across the whole of the species' biogeographical
      range. Variation at both classes of loci was high in the glacial refugium areas
      (REF) and much lower in postglacial expansion areas (PGE), especially in range
      edge populations. Although there was clear evidence that the MHC locus was
      influenced by positive selection in the past, congruence with the neutral markers
      suggested that historical demographic events were the main force shaping MHC
      variation in the PGE area. Both neutral and adaptive genetic variation declined
      with distance from glacial refugia. Nevertheless, there were also some
      indications from differential isolation by distance and allele abundance patterns
      that weak effects of selection have been superimposed on the main drift effect in
      the PGE zone. 

PMID- 24937213
TI  - Mid-ATR-FTIR spectroscopic profiling of HIV/AIDS sera for novel systems
      diagnostics in global health.
AB  - Global health, whether in developed or developing countries, is in need of robust
      systems diagnostics for major diseases, such as HIV/AIDS, impacting the world
      populations. Fourier transform Infrared (FTIR) spectroscopy of serum is a quick
      and reagent-free methodology with which to analyze metabolic alterations such as
      those caused by disease or treatment. In this study, Attenuated Total Reflectance
      Fourier-Transform (ATR-FTIR) Spectroscopy was investigated as a means of
      distinguishing HIV-infected treatment-experienced (HIV(pos) ART(pos), n=39) and
      HIV-infected-treatment-naive (HIV(pos) ART(neg), n=16) subjects from uninfected
      control subjects (n=30). Multivariate pattern recognition techniques, including
      partial least squares discriminant analysis (PLS-DA) and orthogonal partial least
      squares discriminant analysis (OPLS-DA), successfully distinguished sample
      classes, while univariate approaches identified significant differences (p<0.05)
      after Benjamini-Hochberg corrections. OPLS-DA discriminated between all groups
      with sensitivity, specificity, and accuracy of >90%. Compared to uninfected
      controls, HIV(pos) ART(pos) and HIV(pos) ART(neg) subjects displayed significant
      differences in spectral regions linked to lipids/fatty acids (3010 cm(-1)),
      carbohydrates (1299 cm(-1); 1498 cm(-1)), glucose (1035 cm(-1)), and proteins
      (1600 cm(-1); 1652 cm(-1)). These are all molecules shown by conventional
      biochemical analysis to be affected by HIV/ART interference. The biofluid
      metabolomics approach applied here successfully differentiated global metabolic
      profiles of HIV-infected patients and uninfected controls and detected potential
      biomarkers for development into indicators of host response to treatment and/or
      disease progression. Our findings therefore contribute to ongoing efforts for
      capacity-building in global health for robust omics science and systems
      diagnostics towards major diseases impacting population health.

PMID- 24937215
TI  - Direct detection of Mycobacterium avium in environmental water and scale samples
      by loop-mediated isothermal amplification.
AB  - We previously demonstrated the colonization of Mycobacterium avium complex in
      bathrooms by the conventional culture method. In the present study, we aimed to
      directly detect M. avium organisms in the environment using loop-mediated
      isothermal amplification (LAMP), and to demonstrate the efficacy of LAMP by
      comparing the results with those obtained by culture. Our data showed that LAMP
      analysis has detection limits of 100 fg DNA/reaction for M. avium. Using an
      FTA((r)) elute card, DNA templates were extracted from environmental samples from
      bathrooms in the residences of 29 patients with pulmonary M. avium disease. Of
      the 162 environmental samples examined, 143 (88%) showed identical results by
      both methods; 20 (12%) and 123 (76%) samples were positive and negative,
      respectively, for M. avium. Of the remaining 19 samples (12%), seven (5%) and 12
      (7%) samples were positive by the LAMP and culture methods, respectively. All
      samples that contained over 20 colony forming units/primary isolation plate, as
      measured by the culture method, were also positive by the LAMP method. Our data
      demonstrate that the combination of the FTA elute card and LAMP can facilitate
      prompt detection of M. avium in the environment. 

PMID- 24937214
TI  - Self-folding single cell grippers.
AB  - Given the heterogeneous nature of cultures, tumors, and tissues, the ability to
      capture, contain, and analyze single cells is important for genomics, proteomics,
      diagnostics, therapeutics, and surgery. Moreover, for surgical applications in
      small conduits in the body such as in the cardiovascular system, there is a need
      for tiny tools that approach the size of the single red blood cells that traverse
      the blood vessels and capillaries. We describe the fabrication of arrayed or
      untethered single cell grippers composed of biocompatible and bioresorbable
      silicon monoxide and silicon dioxide. The energy required to actuate these
      grippers is derived from the release of residual stress in 3-27 nm thick films,
      did not require any wires, tethers, or batteries, and resulted in folding angles
      over 100 degrees  with folding radii as small as 765 nm. We developed and applied
      a finite element model to predict these folding angles. Finally, we demonstrated
      the capture of live mouse fibroblast cells in an array of grippers and individual
      red blood cells in untethered grippers which could be released from the substrate
      to illustrate the potential utility for in vivo operations.

PMID- 24937216
TI  - Prospective epidemiological pilot study on the morbidity of bathers exposed to
      tropical recreational waters and sand.
AB  - A prospective cohort epidemiological pilot study was performed at three tropical
      beaches with point- and non-point-sources of fecal pollution to characterize the
      risk of illness among swimmers and non-swimmers. There was an increased risk of
      illness in swimmers as compared to non-swimmers, even when waters met current
      microbial standards for recreational water quality. Illnesses included
      gastrointestinal (GI), skin and respiratory symptoms, earache and fever. Odds
      ratios (ORs) ranged from 0.32 to 42.35 (GI illness), 0.69 to 3.12 (skin
      infections), 0.71 to 3.21 (respiratory symptoms), 0.52 to 15.32 (earache) and
      0.80 to 1.68 (fever), depending on the beach sampled. The indicators that better
      predicted the risks of symptoms (respiratory) in tropical recreational waters
      were total (somatic and male-specific) coliphages (OR = 1.56, p < 0.10, R(2) =
      3.79%) and Escherichia coli (OR = 1.38, p < 0.10, R(2) = 1.97%). The present
      study supports the potential of coliphages as good predictors of risks of
      respiratory illness in tropical recreational waters. This is the first study that
      has determined risks of illness after exposure to tropical recreational waters
      with point- and non-point sources of fecal contamination. The results give an
      opportunity to perform epidemiological studies in tropical recreational waters in
      Puerto Rico which can include more participants and other indicators and
      detection techniques. 

PMID- 24937217
TI  - Drinking water quality monitoring using trend analysis.
AB  - One of the common quality parameters for drinking water is residual aluminium.
      High doses of residual aluminium in drinking water or water used in the food
      industry have been proved to be at least a minor health risk or even to increase
      the risk of more serious health effects, and cause economic losses to the water
      treatment plant. In this study, the trend index is developed from scaled
      measurement data to detect a warning of changes in residual aluminium level in
      drinking water. The scaling is based on monotonously increasing, non-linear
      functions, which are generated with generalized norms and moments. Triangular
      episodes are classified with the trend index and its derivative. The severity of
      the situations is evaluated by deviation indices. The trend episodes and the
      deviation indices provide good tools for detecting changes in water quality and
      for process control. 

PMID- 24937218
TI  - Proteomic regulation during Legionella pneumophila biofilm development: decrease
      of virulence factors and enhancement of response to oxidative stress.
AB  - Legionella pneumophila (L. pneumophila) is a Gram-negative bacterium, which can
      be found worldwide in aquatic environments. It tends to persist because it is
      often protected within biofilms or amoebae. L. pneumophila biofilms have a major
      impact on water systems, making the understanding of the bacterial physiological
      adaptation in biofilms a fundamental step towards their eradication. In this
      study, we report for the first time the influence of the biofilm mode of growth
      on the proteome of L. pneumophila. We compared the protein patterns of
      microorganisms grown as suspensions, cultured as colonies on agar plates or
      recovered with biofilms formed on stainless steel coupons. Statistical analyses
      of the protein expression data set confirmed the biofilm phenotype specificity
      which had been previously observed. It also identified dozens of proteins whose
      abundance was modified in biofilms. Proteins corresponding to virulence factors
      (macrophage infectivity potentiator protein, secreted proteases) were largely
      repressed in adherent cells. In contrast, a peptidoglycan-associated lipoprotein
      (Lpg2043) and a peroxynitrite reductase (Lpg2965) were accumulated by biofilm
      cells. Remarkably, hypothetical proteins, that appear to be unique to the
      Legionella genus (Lpg0563, Lpg1111 and Lpg1809), were over-expressed by sessile
      bacteria. 

PMID- 24937219
TI  - The water environment as a source of potentially pathogenic mycobacteria.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous organisms of a wide variety of
      environmental reservoirs, including natural and municipal water, soil, aerosols,
      protozoans, animals and humans. Several of these species are potential pathogens
      which affect human health. The aim of this study was to determine the occurrence
      of NTM in the water environment. Samples were taken from 13 water-related
      facilities including fish ponds, storage ponds, drinking water reservoirs and an
      experimental recirculation system. Altogether, 396 samples of water, sediment and
      aquatic plants were collected and analysed. All samples were examined using
      conventional culture methods. Suspected microbial isolates were subjected to
      polymerase chain reaction analysis and identified using partial sequence analysis
      of the 16S rDNA gene. The culture revealed 94/396 samples (23.7%) that contained
      mycobacteria. Among known NTM we identified potentially pathogenic mycobacteria
      isolated from the fresh water environment for the first time: Mycobacterium
      asiaticum, M. chimaera, M. interjectum, M. kumamotonense, M. lentiflavum, M.
      montefiorense, M. nebraskense, M. paraffinicum and M. simiae. Epidemiologic
      studies suggest that the natural water environment is the principal source of
      human exposure. Our results indicate that besides the well-known potentially
      pathogenic mycobacteria it is important to observe occurrence, proliferation and
      persistence of newly discovered mycobacterial species. 

PMID- 24937220
TI  - The effect of sodium azide concentration on the recovery of enterococci from
      water.
AB  - The ability of Slanetz and Bartley medium to recover chlorine-stressed
      enterococci has been studied. Results showed that chlorine injury significantly
      affected the ability of Slanetz and Bartley medium to recover enterococci while
      lower concentrations of sodium azide in the same basal medium allowed their
      recovery. However, reducing the concentration of sodium azide considerably
      reduced the specificity making it unsuitable for use in the routine examination
      of water. A non-azide-containing medium, Enterolert((r))-DW appeared to be able
      to recover injured and non-injured enterococci with similar efficiency. The data
      presented here suggest that further work is required to improve the recovery of
      chlorine-injured enterococci by Slanetz and Bartley medium. 

PMID- 24937222
TI  - Relating the bivalve shellfish harvesting area classification criteria in the
      United States and European Union programmes.
AB  - Estimation of the level of risk of faecal contamination of shellfish harvesting
      areas is undertaken by monitoring faecal indicator bacteria in seawater samples
      under the United States programme and shellfish flesh samples under the European
      Union (EU) programme. Determining the relationship between the two approaches is
      important for assessing the relative level of public health protection and
      regulating international trade. The relationship was investigated using both
      statistical modelling and simple compliance assessment on large international
      data sets of paired seawater and shellfish samples. The two approaches yielded
      the same conclusions: EU class A is more stringent than the US Approved category
      for all species; the US Restrictive standard is more restrictive than EU class B
      for some bivalve species. Therefore, the classifications under the two programmes
      are not exactly equivalent. 

PMID- 24937221
TI  - Assessment of swimmer behaviors on pool water ingestion.
AB  - Enteric pathogens in pool water can be unintentionally ingested during swimming,
      increasing the likelihood of acute gastrointestinal illness (AGI). AGI cases in
      outbreaks are more likely to submerge heads than non-cases, but an association is
      unknown since outbreak data are self-reported and prone to bias. In the present
      study, head submersion frequency and duration were observed and analyzed for
      associations with pool water ingestion measured using ultra high pressure liquid
      chromatography - tandem mass spectrometry. Frequency of splashes to the face was
      also quantified. Reliable tools that assess activities associated with pool water
      ingestion are needed to identify ingestion risk factors and at-risk populations.
      Objectives were to determine if the observed activities were associated with
      ingestion, and to test environmental sensor and videography assessment tools.
      Greater frequency and duration of head submersion were not associated with
      ingestion, but frequency of splashes to the face, leisurely swimming, and being
      <=18 were. Videography was validated for assessing swimmer head submersion
      frequency. Results demonstrate ingestion risk factors can be identified using
      videography and urine analysis techniques. Expanding surveys to include questions
      on leisure swimming participation and frequency of splashes to the face is
      recommended to improve exposure assessment during outbreak investigations. 

PMID- 24937224
TI  - Quantitative microbial risk assessment related to urban wastewater and lagoon
      water reuse in Abidjan, Cote d'Ivoire.
AB  - We assessed the infection risks related to the use of wastewater in Abidjan, Cote
      d'Ivoire, by using quantitative microbial risk assessment (QMRA). Giardia lamblia
      and Escherichia coli were isolated and identified in wastewater samples from the
      canal and lagoon. The exposure assessment was conducted using a cross-sectional
      survey by questionnaire with 150 individuals who were in contact with the
      wastewater during their daily activities of swimming, fishing, washing, and
      collecting materials for reuse. Risk was characterised using the Monte Carlo
      simulation with 10,000 iterations. Results showed high contamination of water by
      G. lamblia and E. coli (12.8 CFU/100 mL to 2.97 * 10(4)CFU/100 mL and from 0
      cyst/L to 18.5 cysts/L, respectively). Estimates of yearly average infection
      risks for E. coli (90.07-99.90%, assuming that 8% of E. coli were E. coli
      O157:H7) and G. lamblia (9.4-34.78%) were much higher than the acceptable risk
      (10(-4)). These results suggest the need for wastewater treatment plants, raising
      awareness in the population in contact with urban wastewater and lagoon water.
      Our study also showed that QMRA is appropriate to study health risks in settings
      with limited data and budget resources. 

PMID- 24937223
TI  - Ceramic water filters impregnated with silver nanoparticles as a point-of-use
      water-treatment intervention for HIV-positive individuals in Limpopo Province,
      South Africa: a pilot study of technological performance and human health
      benefits.
AB  - Waterborne pathogens present a significant threat to people living with the human
      immunodeficiency virus (PLWH). This study presents a randomized, controlled trial
      that evaluates whether a household-level ceramic water filter (CWF) intervention
      can improve drinking water quality and decrease days of diarrhea in PLWH in rural
      South Africa. Seventy-four participants were randomized in an intervention group
      with CWFs and a control group without filters. Participants in the CWF arm
      received CWFs impregnated with silver nanoparticles and associated safe-storage
      containers. Water and stool samples were collected at baseline and 12 months.
      Diarrhea incidence was self-reported weekly for 12 months. The average diarrhea
      rate in the control group was 0.064 days/week compared to 0.015 days/week in the
      intervention group (p < 0.001, Mann-Whitney). Median reduction of total coliform
      bacteria was 100% at enrollment and final collection. CWFs are an acceptable
      technology that can significantly improve the quality of household water and
      decrease days of diarrhea for PLWH in rural South Africa. 

PMID- 24937225
TI  - Microbiological assessment of private groundwater-derived potable water supplies
      in the Mid-West Region of Ireland.
AB  - Determining the likelihood that groundwater contains faecal coliforms can aid
      water resource management in facilitating the protection of drinking water
      supplies. This study assesses the incidence of the faecal indicator organism
      Escherichia coli in 125 private water supplies (PWSs) serving individual houses
      in the Mid-West Region of Ireland. Two factors, aquifer type and rainfall (mm),
      were chosen as independent variables that can affect the vulnerability of a
      groundwater body. Using a geographical information system, the relative
      hydrogeological and climatological features unique to each sampling location were
      derived. Utilising this information, a logistic regression (LR) model was used to
      predict the probability of contamination of PWSs with E. coli. The model
      contained two independent variables: rainfall (mm; p < 0.001) and aquifer
      characteristics (p = 0.001). The full model, containing both predictors, was
      statistically significant at p < 0.001, indicating that the model distinguished
      between the independent variables' relationship to the incidence of
      contamination. The likelihood of E. coli contamination is greater with increased
      rainfall and in areas where a bedrock aquifer is dominant. The LR model explained
      between 27.4% (Cox and Snell R squared) and 36.8% (Nagelkerke R squared) of the
      variance in contamination and correctly classified 75.2% of cases. 

PMID- 24937226
TI  - Factors influencing householders' access to improved water in low-income urban
      areas of Accra, Ghana.
AB  - We analysed householders' access to improved water for drinking and other
      domestic uses in five selected low-income urban areas of Accra, Ghana using a
      survey of 1,500 households. Our definitions of improved water were different from
      those suggested by the World Health Organization (WHO). The results revealed that
      only 4.4% of the respondents had access to improved drinking water compared to
      40.7% using the WHO definition. However, 88.7% of respondents had access to
      improved water for domestic uses compared to 98.3% using the WHO definition.
      Using logistic regression analysis, we established that the significant
      determinant of householders' access to improved drinking water was income.
      However, for access to improved water for other domestic uses, the significant
      factors were education, income and location of the household. Compared to
      migrants, indigenous people and people from mixed areas were less likely to have
      access to improved water for other domestic purposes. For the analysis using the
      WHO definitions, most of the independent variables were not statistically
      significant in determining householders' access, and those variables that were
      significant generated parameter estimates inconsistent with evidence from the
      literature and anecdotal evidence from officials of public health and water
      supply companies in Ghana. 

PMID- 24937228
TI  - Safety of packaged water distribution limited by household recontamination in
      rural Cambodia.
AB  - Packaged water treatment schemes represent a growing model for providing safer
      water in low-income settings, yet post-distribution recontamination of treated
      water may limit this approach. This study evaluates drinking water quality and
      household water handling practices in a floating village in Tonle Sap Lake,
      Cambodia, through a pilot cross-sectional study of 108 households, approximately
      half of which used packaged water as the main household drinking water source. We
      hypothesized that households purchasing drinking water from local packaged water
      treatment plants would have microbiologically improved drinking water at the
      point of consumption. We found no meaningful difference in microbiological
      drinking water quality between households using packaged, treated water and those
      collecting water from other sources, including untreated surface water, however.
      Households' water storage and handling practices and home hygiene may have
      contributed to recontamination of drinking water. Further measures to protect
      water quality at the point-of-use may be required even if water is treated and
      packaged in narrow-mouthed containers. 

PMID- 24937227
TI  - Removal of indigenous coliphages and enteric viruses during riverbank filtration
      from highly polluted river water in Delhi (India).
AB  - Emerging countries frequently afflicted by waterborne diseases require safe and
      cost-efficient production of drinking water, a task that is becoming more
      challenging as many rivers carry a high degree of pollution. A study was
      conducted on the banks of the Yamuna River, Delhi, India, to ascertain if
      riverbank filtration (RBF) can significantly improve the quality of the highly
      polluted surface water in terms of virus removal (coliphages, enteric viruses).
      Human adenoviruses and noroviruses, both present in the Yamuna River in the range
      of 10(5) genomes/100 mL, were undetectable after 50 m infiltration and
      approximately 119 days of underground passage. Indigenous somatic coliphages,
      used as surrogates of human pathogenic viruses, underwent approximately 5 log10
      removal after only 3.8 m of RBF. The initial removal after 1 m was 3.3 log10, and
      the removal between 1 and 2.4 m and between 2.4 and 3.8 m was 0.7 log10 each. RBF
      is therefore an excellent candidate to improve the water situation in emerging
      countries with respect to virus removal. 

PMID- 24937229
TI  - Microbial source tracking and spatial analysis of E. coli contaminated private
      well waters in southeastern Ontario.
AB  - Private water supplies, which are the primary source of drinking water for rural
      communities in developed countries, are at risk of becoming fecally contaminated.
      It is important to identify the source of contamination in order to better
      understand and address this human health risk. Microbial source tracking methods
      using human, bovine and general Bacteroidales markers were performed on 716 well
      water samples from southeastern Ontario, which had previously tested positive for
      Escherichia coli. The results were then geospatially analyzed in order to
      elucidate contamination patterns. Markers for human feces were found in nearly
      half (49%) of all samples tested, and a statistically significant spatial cluster
      was observed. A quarter of the samples tested positive for only general
      Bacteroidales markers (25.7%) and relatively few bovine specific marker positives
      (12.6%) were found. These findings are fundamental to the understanding of
      pathogen dynamics and risk in the context of drinking well water and will inform
      future research regarding host-specific pathogens in private well water samples. 

PMID- 24937230
TI  - Asynchronous stochastic Boolean networks as gene network models.
AB  - Logical models have widely been used to gain insights into the biological
      behavior of gene regulatory networks (GRNs). Most logical models assume a
      synchronous update of the genes' states in a GRN. However, this may not be
      appropriate, because each gene may require a different period of time for
      changing its state. In this article, asynchronous stochastic Boolean networks
      (ASBNs) are proposed for investigating various asynchronous state-updating
      strategies in a GRN. As in stochastic computation, ASBNs use randomly permutated
      stochastic sequences to encode probability. Investigated by several stochasticity
      models, a GRN is considered to be subject to noise and external perturbation.
      Hence, both stochasticity and asynchronicity are considered in the state
      evolution of a GRN. As a case study, ASBNs are utilized to investigate the
      dynamic behavior of a T helper network. It is shown that ASBNs are efficient in
      evaluating the steady-state distributions (SSDs) of the network with random gene
      perturbation. The SSDs found by using ASBNs show the robustness of the attractors
      of the T helper network, when various stochasticity and asynchronicity models are
      considered to investigate its dynamic behavior.

PMID- 24937232
TI  - Analysis of the structural and functional roles of coupling helices in the ATP
      binding cassette transporter MsbA through enzyme assays and molecular dynamics
      simulations.
AB  - ATP-binding cassette (ABC) transporters are constructed from some common
      structural units: the highly conserved nucleotide-binding domains (NBDs), which
      work as a nucleotide-dependent engine for driving substrate transport, the
      diverse transmembrane domains (TMDs), which create the translocation pathway, and
      the coupling helices (CHs), which are located at the NBD-TMD interface. Although
      the CHs are believed to be essential for NBD-TMD communication, their roles
      remain unclear. In this study, we performed enzyme assays and molecular dynamics
      (MD) simulations of the ABC transporter MsbA and two MsbA mutants in which the
      amino acid residues of one of the CHs were mutated to alanines: (i) wild type
      (Wt), (ii) CH1 mutant (Mt1), and (iii) CH2 mutant (Mt2). The experiments show
      that the CH2 mutation decreases the ATPase activity (kcat) compared with that of
      the Wt (a decrease of 32%), and a nearly equal degree of decrease in the ATP
      binding affinity (Km) was observed for both Mt1 and Mt2. The MD simulations
      successfully accounted for several structural and dynamical origins for these
      experimental observations. In addition, on the basis of collective motion and
      morphing analyses, we propose that the reverse-rotational motions and noddinglike
      motions between the NBDs and TMDs are indispensable for the conformational
      transition between the inward- and outward-facing conformations. In particular,
      CH2 is significantly important for the occurrence of the noddinglike motion.
      These findings provide important insights into the structure-function
      relationship of ABC transporters. 

PMID- 24937231
TI  - Modeling promising nonmyeloablative conditioning regimens in nonhuman primates.
AB  - Minimal conditioning or even no conditioning would be the preferred preparation
      for most gene therapy applications for nonmalignant diseases. However, reduced
      intensity conditioning (RIC) regimens in patients with nonhematologic
      malignancies have not led to long-term engraftment unless a selective advantage
      was present for the transplanted donor cells. Similar findings have also been
      observed in a number of large animal studies. Inadequate myelosuppression levels
      were thought to be responsible for the outcomes. To address this issue several
      innovative protocols in small animals have been presented with selective
      hematopoietic myelosuppression and less systemic toxicity. Such protocols
      promised to curb the transplant-related morbidity and mortality in myeloablative
      conditioning and provide effective long-term engraftment, especially in patients
      with gene-corrected autografts. In the present study we have tested some of these
      promising RIC regimens in nonhuman primates, a clinically relevant large animal
      model. Our data suggest that transient myelosuppression induced by anti-c-Kit
      antibody in conjunction with low-dose irradiation may lead to long-term
      engraftment, albeit at low levels. The animals with busulfan conditioning with or
      without anti-c-Kit that received gene-modified autologous transplants with green
      fluorescent protein expression had similar myelosuppression, but failed long-term
      engraftment and despite immunosuppressive treatment had all the hallmarks seen
      previously in similar models without immunosuppression. Our preliminary data
      expand current knowledge of RIC and emphasize the need to explore whether
      specific and directed myelosuppression alone is adequate in the absence of
      microenvironmental modulation, or whether innovative combinations are necessary
      for safe and effective engraftment.

PMID- 24937234
TI  - Editorial.

PMID- 24937233
TI  - Selective aerobic oxidation of alcohols to aldehydes, carboxylic acids, and
      imines catalyzed by a Ag-NHC complex.
AB  - Silver NHC catalysts have been developed for the selective oxidation of alcohols
      to aldehydes or carboxylic acids in the presence of BnMe3NOH or KOH under dry
      air. The aerobic oxidation conditions are mild, and the yield is excellent.
      Further tandem catalysis enables the one-pot synthesis of imines in excellent
      yield. Only 0.1 mol % of the catalyst is required. 

PMID- 24937235
TI  - Contacts of suicide attempters with healthcare services in Pecs and Bern in the
      WHO/EURO Multicentre Study on Parasuicide.
AB  - The aim of this study was to compare patterns of contact made by patients with
      GPs and other healthcare professionals in two European cities prior to attempting
      suicide. The objective was to determine whether differences between a public and
      a private healthcare system could be a possible factor influencing the help
      seeking behaviour of suicide attempters. Within the frame of the WHO/EURO
      Multicentre Study on Parasuicide, structured interviews were conducted with
      suicide attempters in Pecs, Hungary (n=101) and Bern, Switzerland (n=66). In
      Bern, slightly more patients visited their GPs throughout the year. However,
      within the last week before the suicide attempt, twice as many Hungarian patients
      went to see a GP compared with the Bern sample. Almost the same proportion of the
      patients had suicidal ideation, but in Pecs more than a quarter of them and in
      Bern half of them talked about their suicidal thoughts. In the Hungarian sample,
      more patients were prescribed medication and almost half of them used these drugs
      for self-poisoning compared to over a quarter in Bern. The differences in help
      seeking behaviour between the two samples may be related to the higher number of
      practising GPs and a more consistent patient-doctor relationship in Bern. It is
      likely that a consistent and personal relationship with a medical helper or
      system (e.g. GP as gatekeeper) facilitates the communication of suicidal
      ideation. 

PMID- 24937236
TI  - Sleep deprivation in depression: An integrative approach.
AB  - The question as to whether the beneficial effect of sleep deprivation in
      depression is related to the increased wakefulness or to the sleep suppression by
      itself, is made moot by the search activity concept. According to this concept,
      rapid eye movement (REM) sleep is functionally deficient in depression and
      increases feelings of helplessness and hopelessness instead of restoring mood and
      search activity. Thus, REM sleep deprivation, either selective or not, is
      beneficial by breaking a vicious circle: depression in wakefulness...giving up
      (helplessness) in dream scenario...increased depression in the subsequent
      wakefulness. In addition, sleep deprivation is an important challenge for the
      depressed patient. The ability to confront this challenge and maintain
      wakefulness has a positive outcome on depression, especially when wakefulness is
      accompanied by active behavior. 

PMID- 24937237
TI  - Correlates of suicidal ideation in general healthcare patients - Results of the
      WHO Collaborative Study on Psychological Problems in General Health Care (WHO
      PPGHC).
AB  - In the WHO study on Psychological Problems in General Health Care (WHO-PPGHC), a
      random sample of 5438 patients from 15 international centres were investigated to
      study prevalence and type of mental disorders by use of standardized methods.
      Using the General Health Questionnaire, 9.7% of the practice attenders admitted
      that they have or recently had suicidal ideations. In a logistic regression
      analysis, predictors of suicidal ideation were hopelessness, presence of an ICD
      10 diagnosis, social disability in terms of occupational role functioning and
      daily routine, and lack of social adaptation in terms of lower age and being less
      educated. The predictors are discussed in an explanatory model of suicidal
      ideation in general healthcare. Implications for patient care in general
      healthcare are discussed. 

PMID- 24937238
TI  - Do we manage deliberate self-harm appropriately? Characteristics of general
      hospital patients who are offered psychiatric aftercare.
AB  - BACKGROUND The appropriateness of psychiatric management decisions following an
      episode of deliberate self-harm is under-researched. AIM To determine whether the
      offer of follow-up or psychiatric admission by psychiatric doctors is related to
      known predictors of repetition of self-harm or completed suicide, and recognition
      of a depressive disorder. METHODS Prospective survey of 158 adult self-harm
      referrals from the general hospital. RESULTS Offer of aftercare was significantly
      associated with a definite wish to die at the time of the attempt (P<0.001),
      Beck's Suicide Intent score (P=0.001), Beck's Hopelessness score (P=0.001), age
      (P<0.01) and an ICD-10 diagnosis of depression (P<0.001). Psychiatric admission
      was more likely for men (P=0.01) and accommodation problems (P=0.04) and less
      likely for relationship problems (P=0.01). CONCLUSIONS Psychiatrists are
      selectively admitting or following up patients from established high-risk groups.
      Given the limitations of suicide prevention and mental health resources, their
      management is appropriate. 

PMID- 24937239
TI  - Factitious Disorders: the Baron's legacy.
AB  - Our understanding of factitious disorders has expanded from that of medical and
      surgical exotica into that of a much broader psychiatric disorder. Patients can
      be divided into a nuclear group (classical Munchausen), a larger non-nuclear and
      less socially deviant group, and children involved by proxy. There are many
      aetiological theories, ranging from the psychoanalytic to the organic, and at
      least some cases are learned at home. Physicians and other professionals must be
      familiar with the general features of these disorders and have some idea of the
      potential breadth of presentation. Diagnosis is based on a high index of
      suspicion, some knowledge of the literature, and sound history taking, including
      the collection of substantiating evidence (e.g. reports from other treating
      agencies or from relatives). Management is controversial. Prolonged psychotherapy
      may help some adult cases. Child safety issues are paramount in the case of
      factitious disorder by proxy. Pseudoseizures are given special attention. 

PMID- 24937240
TI  - Olfactory reference syndrome manifests in a variety of psychiatric disorders.
AB  - Olfactory reference syndrome (ORS) is a rare psychiatric condition characterized
      by isolated olfactory hallucinations or illusionary misinterpretations of odours
      with delusional self-reference and a typical contrite reaction. The
      aetiopathology of the disorder is unclear. Three cases of ORS are presented,
      which show the typical clinical symptom constellation, while pointing to various
      underlying psychiatric illnesses and differing treatment responses. Nosological
      aspects are discussed on the basis of the available literature. 

PMID- 24937241
TI  - "Value for money" in treating Alzheimer's disease with the new cholinesterase
      inhibitors.
AB  - The absolute number of dementia cases is likely to increase due to the impending
      demographic changes. Several cost-of-illness studies of Alzheimer's disease,
      mainly from a societal perspective in developed countries, have demonstrated a
      huge economic burden. A substantial component of this huge economic burden is the
      direct costs of institutionalization and the indirect cost incurred by informal
      carers. This huge economic burden is of great interest because of the emergence
      of several cholinesterase inhibitors with proven efficacy in the treatment of
      Alzheimer's disease. Several cost-effectiveness studies of these drugs, based
      mainly on Markov modelling techniques and using data from population-based
      epidemiological studies and efficacy trials, have indicated that these drugs are
      cost-effective. A theoretical delay in placement into a residential or a nursing
      home and consequent cost savings may explain this cost-effectiveness. In the UK,
      although health authorities would fund the prescription of these drugs, social
      services would benefit from the cost savings; thus there is little financial
      incentive for health authorities to fund these drugs. 

PMID- 24937242
TI  - Meige's syndrome associated with neuroleptic treatment and alcohol abuse.
AB  - Meige's syndrome is characterized by blepharospasm and oromandibular dystonia. A
      case is presented in association with long-term neuroleptic administration and
      alcohol abuse. This syndrome may be a variant of tardive dystonia. 

PMID- 24937243
TI  - Substantial increase in number and dosage of antipsychotics in non-responsive vs.
      responsive schizophrenia inpatients.
AB  - INTRODUCTION Current clinical guidelines recommend the use of a single
      antipsychotic drug for acute schizophrenic exacerbation. We examined whether this
      approach is also employed in non-responsive schizophrenia inpatients. METHODS
      Forty-one consecutively admitted schizophrenic inpatients were assigned into a
      study group [n=22; non-responsive (DeltaBPRS<10%) to two consecutive trials of
      antipsychotics prior to and following 24 weeks of hospitalization] and a
      comparison group [n=19; partial-to-good (DeltaBPRS=10-27%) responders under
      similar settings]. RESULTS The number and dosage of antipsychotics were increased
      by 34% and 40% (P=0.016 and P=0.062, respectively) in the study group compared to
      the comparison subjects following 24 weeks of hospitalization. In the study
      group, a significant correlation was found between the number of antipsychotics
      administered and their dose (r=0.22, n=88, P=0.04). CONCLUSION Clinicians do not
      comply with evidence-based algorithms, and treat non-responsive schizophrenia
      inpatients with a combination of antipsychotics and at substantially higher doses
      compared to partial-to-good responders. Our findings discourage such practice. 

PMID- 24937244
TI  - Efficacy and tolerability of quetiapine in patients with schizophrenia switched
      from other antipsychotics.
AB  - OBJECTIVE The Seroquel Patient Evaluation on Changing Treatment Relative to Usual
      Medication (SPECTRUM) study assessed the efficacy and tolerability of quetiapine
      (SeroquelTM) in patients with schizophrenia switched from treatments providing
      suboptimal outcomes. METHODS This was an international, open-label, non
      comparative study, designed with titration to 400 mg/day quetiapine over 7 days,
      then flexible dosing (300-750 mg/day) for 11 weeks. Efficacy was assessed with
      the Positive and Negative Syndrome Scale (PANSS); Clinical Global Impression
      (CGI) Severity of Illness and Global Improvement scores; and the Calgary
      Depression Scale for Schizophrenia (CDSS). Clinical benefit and tolerability were
      also assessed. RESULTS The mean modal dose of quetiapine was 505 mg/day; 509
      patients switched to quetiapine from olanzapine (13%), risperidone (11%),
      conventional antipsychotics (37%) and combinations of antipsychotics (28%),
      amongst others. Significant decreases in CGI Severity of Illness and PANSS scores
      and a significant improvement in CDSS score resulted from the switch (all P<0.001
      versus baseline). There were significant reductions in extrapyramidal symptoms
      (EPS) on the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS) (both
      P<0.001 versus baseline) and a low incidence of EPS-related adverse events
      (4.7%). CONCLUSION Results indicate that switching to quetiapine was clinically
      beneficial for patients with poor efficacy or intolerable side effects on their
      previous antipsychotic medication. 

PMID- 24937245
TI  - Olanzapine use in acute porphyria.
AB  - This report describes the use of olanzapine in the treatment of a patient with
      hereditary coproporphyria. This patient suffered from paranoid delusions, poor
      self-care and anxiety symptoms. The patient was commenced on olanzapine with a
      good clinical response, and without significant adverse effects. This suggests
      that olanzapine is a safe and effective treatment of psychotic symptoms in acute
      porphyrias. 

PMID- 24937246
TI  - Neuropathology and genetics of dementia.

PMID- 24937247
TI  - Hilary Koprowski, MD: A lifetime of work.

PMID- 24937248
TI  - Hilary Koprowski, MD December 5, 1916-April 11, 2013.

PMID- 24937249
TI  - Remembrances of Hilary Koprowski from a Surgeon's Perspective.

PMID- 24937250
TI  - Nanotechnology-based approaches for the development of diagnostics, therapeutics,
      and vaccines.
AB  - The architecture of nanoparticles of biological origin, generally also known as
      bionanoparticles, presents several features that are ideal for their use in
      developing diagnostics, therapeutics, and vaccines. In this regard, particles
      formed by viral proteins using recombinant DNA technology resemble authentic
      virus particles. However, they lack infectivity due to the absence of genetic
      components such as DNA or RNA. Hence, they are designated as virus-like particles
      (VLP). VLPs possess the following characteristics: (1) they can be generated by
      either a single or a few viral proteins; (2) their size, formed by viral
      proteins, is in the range of 20 to100 nm; (3) the number of protein molecules
      required for particle assembly is from hundreds to thousands, depending on the
      VLP; (4) the protein(s) responsible for their assembly are amenable for
      manipulation; and (5) multiple proteins/peptides can be incorporated into a VLP.
      The potential advantages of VLPs directed by retroviral proteins are discussed in
      this review. 

PMID- 24937252
TI  - Characterization of the degradation products of a color-changed monoclonal
      antibody: tryptophan-derived chromophores.
AB  - We describe the characterization of degradation products responsible for color
      change in near UV-visible light-irradiated and heat-stressed monoclonal antibody
      (mAb) drug product in liquid formulation. The treated samples were characterized
      using reversed-phase HPLC and size-exclusion HPLC with absorption spectroscopy.
      Both methods showed color change was due to chromophores formed on the mAb but
      not associated with the formulation excipients in both light-irradiated and heat
      stressed mAb samples. These chromophores were further located by a new peptide
      mapping methodology with a combination of mass spectrometry and absorption
      spectroscopy. Mass spectrometry identified the major tryptophan oxidation
      products as kynurenine (Kyn), N-formylkynurenine (NFK), and hydroxytryptophan (OH
      Trp). The absorption spectra showed that each of the tryptophan oxidation
      products exhibited a distinct absorption band above 280 nm shifted to the longer
      wavelengths in the order of OH-Trp < NFK < Kyn. The Kyn-containing peptide was
      detected by absorption at 420 nm. No new absorption bands were observed for
      either methionine or histidine oxidation products. This confirmed that tryptophan
      oxidation products, but not methionine and histidine oxidation products, were
      responsible for the color change. It is worth noting that a new oxidation product
      with the loss of hydrogen (2 Da mass decrease) for Trp-107 of the heavy chain was
      identified in the heat-stressed mAb sample. This oxidized tryptophan residue
      exhibited a distinct absorption band at the maximum absorbance wavelength 335 nm,
      which is responsible for the color change to yellow. This study showed that the
      new peptide mapping methodology with a combination of mass spectrometry and
      absorption spectroscopy is useful to identify tryptophan oxidation products as
      chromophores responsible for color change in stressed mAb drug product. 

PMID- 24937251
TI  - Expression of recombinant vaccines and antibodies in plants.
AB  - Plants are able to perform post-translational maturations of therapeutic proteins
      required for their functional biological activity and suitable in vivo
      pharmacokinetics. Plants can be a low-cost, large-scale production platform of
      recombinant biopharmaceutical proteins such as vaccines and antibodies. Plants,
      however, lack mechanisms of processing authentic human N-glycosylation, which
      imposes a major limitation in their use as an expression system for therapeutic
      glycoproducts. Efforts have been made to circumvent plant-specific N
      glycosylation, as well as to supplement the plant's endogenous system with human
      glycosyltransferases for non-immunogenic and humanized N-glycan production.
      Herein we review studies on the potential of plants to serve as production
      systems for therapeutic and prophylactic biopharmaceuticals. We have especially
      focused on recombinant vaccines and antibodies and new expression strategies to
      overcome the existing problems associated with their production in plants. 

PMID- 24937254
TI  - Factors that influence functional outcome after total or subtotal scapulectomy:
      Japanese Musculoskeletal Oncology Group (JMOG) study.
AB  - BACKGROUND: Scapulectomy requires not only joint resection but also wide
      resection of the shoulder girdle muscles. Even the significance of reconstruction
      has not yet been determined because of the difficulties in comparing the
      different conditions. The purpose of this study was to investigate factors that
      influence functional outcomes after scapulectomy in a multicenter study. METHODS:
      This retrospective study comprised 48 patients who underwent total or subtotal
      scapulectomy and were followed for at least one year after surgery. Patients were
      registered at the Japanese Musculoskeletal Oncology Group affiliated hospitals.
      Soft tissue reconstruction for joint stabilization was performed when there was
      enough remaining tissue for reconstruction of the rotator cuff and tendons. In 23
      cases, humeral suspension was performed. The average follow-up period was 61.9
      months. Multivariate analysis was performed using the patient's background to
      determine which factors influence the Enneking functional score or active range
      of motion. RESULTS: The average functional score was 21.1 out of 30. Active
      shoulder range of motion was 42.7 degree in flexion, 39.7 degree in abduction,
      49.6 degree of internal rotation and 16.8 degree of external rotation. The amount
      of remaining bone influenced functional outcome, which means that preserving the
      glenoid or the acromion lead to better function compared to total scapulectomy
      (p<0.01). Factors that influenced each functional measure include the amount of
      remaining bone, soft tissue reconstruction, the length of the resected humerus
      and nerve resection (p<0.05). CONCLUSION: Although shoulder function was almost
      eliminated following total or subtotal scapulectomy, minimal resection of bone,
      and soft tissue reconstruction should lead to better function.

PMID- 24937256
TI  - Bioenergetics in chicken embryo fibroblast cells: evidence of lower proton leak
      in spontaneously immortalized chicken embryo fibroblasts compared to young and
      senescent primary chicken embryo fibroblast cells.
AB  - A spontaneously immortalized chicken embryo fibroblast (CEF) cell line (DF-1) is
      known to exhibit faster growth rate and greater sensitivity to oxidative stress
      compared to the primary parent CEF (pCEF1 degrees ) cells. Thus, major objectives
      of this study were to assess cell bioenergetics in pCEF1 degrees  and DF-1 cells
      under control conditions and in response to 4-hydroxy 2-nonenal (4-HNE) induced
      oxidative challenge. Cell bioenergetics were assessed by flux analysis of oxygen
      consumption rate (OCR). Under control conditions, DF-1 cells had higher OCR
      associated with ATP synthase activity and mitochondrial oxygen reserve capacity
      as well as lower OCR due to proton leak and non-mitochondrial cytochrome c
      oxidase activity. In response to 4-HNE (0 to 30 MUM), DF-1 cells were more
      sensitive to oxidant challenge than both young (passage 8) and senescent (passage
      19) pCEF1 degrees  cells. Both passages 8 and 19 pCEF1 degrees  cells exhibited
      higher proton leak in response to 4-HNE, but this was not observed in DF-1 cells.
      Inducible proton leak occurs by 4-HNE stimulated activation of uncoupling protein
      (UCP) and adenine nucleotide translocase (ANT). From mRNA expression data
      indicated that ANT and avian UCP were down-regulated and up-regulated,
      respectively, in DF-1 compared to pCEF1 degrees  cells. Thus, we hypothesize that
      DF-1 cells are unable to increase proton leak due to lower expression of ANT, but
      not avian UCP, and this inability to increase proton leak contributes to greater
      susceptibility to oxidative stress of DF-1 cells compared to pCEF1 degrees 
      cells.

PMID- 24937255
TI  - Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in
      altered liver transcriptomic response.
AB  - Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian
      and military settings. Resuscitation often results in reperfusion injury and
      survivors are susceptible to developing multiple organ failure (MOF). The impact
      of fed state on the overall response to shock and resuscitation has been explored
      in some murine models but few clinically relevant large animal models. We have
      previously used metabolomics to establish that the fed state results in a
      different metabolic response in the porcine liver following hemorrhagic shock and
      resuscitation. In this study, we used our clinically relevant model of
      hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if
      the liver transcriptomic response is also altered with respect to fed state.
      Functional analysis of the response to shock and resuscitation confirmed several
      typical responses including carbohydrate metabolism, cytokine inflammation,
      decreased cholesterol synthesis, and apoptosis. Our findings also suggest that
      the fasting state, relative to a carbohydrate prefed state, displays decreased
      carbohydrate metabolism, increased cytoskeleton reorganization and decreased
      inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests
      that this is a consequence of a shrunken, catabolic state of the liver cells
      which provides an anti-inflammatory condition that partially mitigates
      hepatocellar damage. 

PMID- 24937258
TI  - Digestive efficiencies are independent of gut passage times in rainbow skinks
      (Trachylepis margaritifer).
AB  - Constraints on physiological processes imposed on ectotherms by environmental
      temperatures can be severe, affecting many aspects of their biology. Included in
      the suite of physiological processes affected is gut motility, with below optimum
      temperatures generally resulting in slow gut passage. Trachylepis margaritifer
      (rainbow skink) however presents an unusual pattern whereby gut passage time
      decreases at a low temperature compared to when at an intermediate temperature.
      It has been suggested that this may be a 'cutting-your-losses' response whereby
      nutritional gain is sacrificed by voiding the digesta to reduce the risk of these
      rotting within the gut at these low temperatures, and if this is so, it should
      result in reduced digestive performance at 25 degrees C. We tested this
      hypothesis by measuring appetite, apparent digestive efficiency (ADE) and
      apparent assimilation efficiency (AAE) in T. margaritifer. We found that although
      temperature significantly affected appetite and gut passage time, it did not
      affect digestive efficiency. Both ADE (>90%) and AAE (>80%) were high and
      temperature-independent across the range tested. Thus, the 'cutting-your-losses'
      hypothesis does not explain faster gut passage at 25 degrees C. High digestive
      parameters could be maintained by increasing concentrations of digestive enzyme
      at low temperatures but remains to be tested in this species. 

PMID- 24937257
TI  - Changes in calpains and calpastatin in the soleus muscle of Daurian ground
      squirrels during hibernation.
AB  - We investigated changes in muscle mass, calpains, calpastatin and Z-disk
      ultrastructure in the soleus muscle (SOL) of Daurian ground squirrels
      (Spermophilus dauricus) after hibernation or hindlimb suspension to determine
      possible mechanisms by which muscle atrophy is prevented in hibernators.
      Squirrels (n=30) were divided into five groups: no hibernation group (PRE, n=6);
      hindlimb suspension group (HLS, n=6); two month hibernation group (HIB, n=6); two
      day group after 90+/-12 days of hibernation (POST, n=6); and forced exercise
      group (one time forced, moderate-intensity treadmill exercise) after arousal (FE,
      n=6). Activity and protein expression of calpains were determined by casein
      zymography and western blotting, and Z-disk ultrastructure was observed by
      transmission electron microscopy. The following results were found. Lower body
      mass and higher SOL muscle mass (mg) to total body mass (g) ratio were observed
      in HIB and POST; calpain-1 activity increased significantly by 176% (P=0.034) in
      HLS compared to the PRE group; no significant changes were observed in calpain-2
      activity. Protein expression of calpain-1 and calpain-2 increased by 83%
      (P=0.041) and 208% (P=0.029) in HLS compared to the PRE group, respectively;
      calpastatin expression increased significantly by 180% (P<0.001) and 153%
      (P=0.007) in HIB and POST, respectively; the myofilaments were well-organized,
      and the width of the sarcomere and the Z-disk both appeared visually similar
      among the pre-hibernation, hibernating and post-hibernation animals. Inhibition
      of calpain activity and consequently calpain-mediated protein degradation by
      highly elevated calpastatin protein expression levels may be an important
      mechanism for preventing muscle protein loss during hibernation and ensuring that
      Z-lines remained ultrastructurally intact.

PMID- 24937259
TI  - Molecular characterization of a cDNA encoding red pigment-concentrating hormone
      in black tiger shrimp Penaeus monodon: Implication of its function in molt and
      osmoregulation.
AB  - Red pigment-concentrating hormone (RPCH) is a member of the AKH/RPCH peptide
      family present mainly in crustaceans and insects. Insect AKH is responsible for
      metabolic functions whereas RPCH plays a major role in the aggregation of red
      chromatophores in crustaceans. In this study, a full-length cDNA of RPCH of the
      black tiger shrimp, Penaeus monodon (PmRPCH) was cloned by Rapid Amplification of
      cDNA Ends strategies from the eyestalk RNA. A 770 bp full-length PmRPCH cDNA
      harbored 279 bp of an open reading frame encoding a signal peptide of 21 amino
      acid residues, an 8 amino acid mature RPCH peptide, followed by 61 amino acid
      residues of a RPCH precursor-related peptide. The highest levels of PmRPCH mRNA
      expression were detected in eyestalks while lower expression was found in other
      nervous tissues i.e. brain, thoracic ganglia and abdominal nerve cord. Expression
      of PmRPCH was transiently stimulated upon hypersalinity change within 12 h
      suggesting its osmoregulatory function. During the molting cycle, PmRPCH in the
      eyestalk was expressed at the lowest level in the early pre-molt stage (D0), then
      gradually increased over the pre-molt period and reached the highest level in the
      late pre-molt (D4) and post-molt (AB) stages. RPCH peptide at a dose of 100 pmol
      also increased gill Na(+)/K(+) ATPase activity in 36-48 h after injection.
      However, PmRPCH did not accelerate the duration of molting cycle. Our results
      provide the first evidence on the potential function of PmRPCH in molting,
      probably by mediating hemolymph osmolality and ion transport enzymes during the
      late pre-molt stage.

PMID- 24937260
TI  - Multifactorial, site-specific recurrence models after radical cystectomy for
      urothelial carcinoma: external validation in a cohort of Korean patients.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of site-specific
      recurrence models after radical cystectomy in the Korean population. MATERIALS
      AND METHODS: We conducted a review of an electronic medical record of 572
      patients who underwent radical cystectomy for urothelial carcinoma of the
      bladder. Primary end point was the site-specific recurrence after radical
      cystectomy. RESULTS: The median follow-up in the validation cohort was 42.3
      months (interquartile range: 23.0-89.3 months). During the follow-up period,
      there were 165 patients (28.8%), 85 (14.9%), 31 (5.4%), and 78 (13.6%) who
      recurred in abdomen/pelvis, thoracic region, upper urinary tract, and bone,
      respectively. The c-indices of abdomen/pelvis, thoracic region, upper urinary
      tract, and bone models 3 years after radical cystectomy were 0.69 (95% confidence
      interval [CI], 0.65-0.73), 0.69 (95% CI, 0.64-0.75), 0.61 (95% CI, 0.52-0.69),
      and 0.65 (95% CI, 0.59-0.71), respectively. Kaplan-Meier curves demonstrated that
      models discriminated well and log-rank test were all highly significant (all
      p<0.001), except upper urinary tract model (p = 0.366). Decision curve analysis
      revealed that the use of prediction models for abdomen/pelvis, thoracic region,
      and bone recurrence was associated with net benefit gains relative to the treat
      all strategy, but not the model for upper urinary tract recurrence. CONCLUSIONS:
      Abdomen/pelvis, thoracic region, and bone models demonstrate moderate
      discrimination, adequate calibration, and meaningful net benefit gains, whereas
      upper urinary tract model does not seem applicable to patients from Asia because
      it has suboptimal accuracy.

PMID- 24937261
TI  - Gut microbes contribute to nitrogen provisioning in a wood-feeding cerambycid.
AB  - Xylophagous insects often thrive on nutritionally suboptimal diets through
      symbiotic associations with microbes that supplement their nutritional
      requirements, particularly nitrogen. The wood-feeding cerambycid Anoplophora
      glabripennis (Motschulsky) feeds on living, healthy host trees and harbors a
      diverse gut microbial community. We investigated gut microbial contributions to
      larval nitrogen requirements through nitrogen fixing and recycling (urea
      hydrolysis) processes, using a combination of molecular, biochemical, and stable
      isotope approaches. Genes and transcripts of conserved regions of the urease
      operon (ureC) and nitrogen fixing (nif) regulon (nifH) were detected in A.
      glabripennis eggs and larvae from naturally infested logs and from larvae reared
      on artificial diet. Significant nitrogen fixation and recycling were documented
      in larvae using (15)N2 gas and (15)N-urea, respectively. Subsequent (15)N-routing
      of incorporated recycled nitrogen into larval essential and nonessential amino
      acids was shown for (15)N-urea diet-fed larvae. Results from this study show
      significant gut microbial contributions to this insect's metabolic nitrogen
      utilization through nitrogenous waste product recycling and nitrogen fixation. 

PMID- 24937262
TI  - Feeding regulation in Drosophila.
AB  - Neuromodulators play a key role in adjusting animal behavior based on
      environmental cues and internal needs. Here, we review the regulation of
      Drosophila feeding behavior to illustrate how neuromodulators achieve behavioral
      plasticity. Recent studies have made rapid progress in determining molecular and
      cellular mechanisms that translate the metabolic needs of the fly into changes in
      neuroendocrine and neuromodulatory states. These neuromodulators in turn promote
      or inhibit discrete feeding behavioral subprograms. This review highlights the
      links between physiological needs, neuromodulatory states, and feeding decisions.

PMID- 24937263
TI  - N- and O-acetylation of threonine residues in the context of proteomics.
AB  - The detection of post-translational modifications (PTMs) of proteins is a matter
      of intensive research. Among all possible pitfalls that may lead to
      misidentifications, the chemical stability of modified peptides is scarcely
      questioned. Global proteomic studies devoted to protein acetylation are becoming
      popular. Thus, we were concerned about the intrinsic stability of O-acetylated
      peptides because of the O-N acyl transfer reactivity occurring when an amino
      moiety is present in the vicinity of the acylated hydroxyl group. Here, the
      behavior of isomeric O- and N-acetylated, N-terminal threonine-containing
      peptides was explored in a standard proteomic workflow. We demonstrated a strong
      chemical instability of O-acetylation, which prevents its detection. 

PMID- 24937264
TI  - Risk stratification for advanced colorectal neoplasia according to fecal
      hemoglobin concentration in a colorectal cancer screening program.
AB  - BACKGROUND & AIMS: The latest generation of fecal immunochemical tests (FIT)
      allows for quantitation of hemoglobin in feces, allowing for selection of optimal
      cut-off concentrations. We investigated whether individuals with positive results
      from quantitative FITs, in combination with other factors, could be identified as
      being at greatest risk for advanced colorectal neoplasia. METHODS: In a
      retrospective study, we analyzed data from a consecutive series of 3109
      participants with positive results from FITs (>=20 MUg/g of feces) included in
      the first round of the Barcelona colorectal cancer screening program, from
      December 2009 through February 2012. All participants underwent colonoscopy and
      were assigned to groups with any advanced colorectal neoplasia or with
      nonadvanced colorectal neoplasia (but with another diagnosis or normal
      examination findings). RESULTS: Median fecal hemoglobin concentrations were
      significantly higher in participants with advanced colorectal neoplasia (105
      MUg/g; interquartile range, 38-288 MUg/g) compared with participants with
      nonadvanced colorectal neoplasia (47 MUg/g; interquartile range, 23-119 MUg/g) (P
      < .001). Positive predictive values for advanced colorectal neoplasia, determined
      using arbitrary fecal hemoglobin concentrations, differed with sex and age.
      Multivariate logistic regression analysis identified sex (men: odds ratio [OR],
      2.07; 95% confidence interval, 1.78-2.41), age (60-69 y: OR, 1.24; 95% confidence
      interval, 1.07-1.44), and fecal hemoglobin concentration (>177 MUg/g: OR, 3.80;
      95% confidence interval, 3.07-4.71) as independent predictive factors for
      advanced colorectal neoplasia. Combining these factors, we identified 16 risk
      categories associated with different probabilities of identifying advanced
      colorectal neoplasia. Risk for advanced colorectal neoplasia increased 11.46-fold
      among individuals in the highest category compared with the lowest category;
      positive predictive values ranged from 21.3% to 75.6%. CONCLUSIONS: Fecal
      hemoglobin concentration, in addition to sex and age, in individuals with
      positive results from FITs can be used to stratify probability for the detection
      of advanced colorectal neoplasia. These factors should be used to prioritize
      individuals for colonoscopy examination.

PMID- 24937265
TI  - Risk of upper gastrointestinal bleeding from different drug combinations.
AB  - BACKGROUND & AIMS: Concomitant use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) and low-dose aspirin increases the risk of upper gastrointestinal
      bleeding (UGIB). Guidelines suggest avoiding certain drug combinations, yet
      little is known about the magnitude of their interactions. We estimated the risk
      of UGIB during concomitant use of nonselective (ns)NSAIDs, cyclooxygenase -2
      selective inhibitors (COX-2 inhibitors), and low-dose aspirin with other drugs.
      METHODS: We performed a case series analysis of data from 114,835 patients with
      UGIB (930,888 person-years of follow-up) identified from 7 population-based
      health care databases (approximately 20 million subjects). Each patient served as
      his or her own control. Drug exposure was determined based on prescriptions of
      nsNSAIDs, COX-2 inhibitors, or low-dose aspirin, alone and in combination with
      other drugs that affect the risk of UGIB. We measured relative risk (incidence
      rate ratio [IRR] during drug exposure vs nonexposure) and excess risk due to
      concomitant drug exposure (relative excess risk due to interaction [RERI]).
      RESULTS: Monotherapy with nsNSAIDs increased the risk of diagnosis of UGIB (IRR,
      4.3) to a greater extent than monotherapy with COX-2 inhibitors (IRR, 2.9) or low
      dose aspirin (IRR, 3.1). Combination therapy generally increased the risk of
      UGIB; concomitant nsNSAID and corticosteroid therapies increased the IRR to the
      greatest extent (12.8) and also produced the greatest excess risk (RERI, 5.5).
      Concomitant use of nsNSAIDs and aldosterone antagonists produced an IRR for UGIB
      of 11.0 (RERI, 4.5). Excess risk from concomitant use of nsNSAIDs with selective
      serotonin reuptake inhibitors (SSRIs) was 1.6, whereas that from use of COX-2
      inhibitors with SSRIs was 1.9 and that for use of low-dose aspirin with SSRIs was
      0.5. Excess risk of concomitant use of nsNSAIDs with anticoagulants was 2.4, of
      COX-2 inhibitors with anticoagulants was 0.1, and of low-dose aspirin with
      anticoagulants was 1.9. CONCLUSIONS: Based on a case series analysis, concomitant
      use of nsNSAIDs, COX-2 inhibitors, or low-dose aspirin with SSRIs significantly
      increases the risk of UGIB. Concomitant use of nsNSAIDs or low-dose aspirin, but
      not COX-2 inhibitors, with corticosteroids, aldosterone antagonists, or
      anticoagulants produces significant excess risk of UGIB.

PMID- 24937266
TI  - Prion protein interaction with soil humic substances: environmental implications.
AB  - Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative
      disorders caused by prions. Animal TSE include scrapie in sheep and goats, and
      chronic wasting disease (CWD) in cervids. Effective management of scrapie in many
      parts of the world, and of CWD in North American deer population is complicated
      by the persistence of prions in the environment. After shedding from diseased
      animals, prions persist in soil, withstanding biotic and abiotic degradation. As
      soil is a complex, multi-component system of both mineral and organic components,
      it is important to understand which soil compounds may interact with prions and
      thus contribute to disease transmission. Several studies have investigated the
      role of different soil minerals in prion adsorption and infectivity; we focused
      our attention on the interaction of soil organic components, the humic substances
      (HS), with recombinant prion protein (recPrP) material. We evaluated the kinetics
      of recPrP adsorption, providing a structural and biochemical characterization of
      chemical adducts using different experimental approaches. Here we show that HS
      act as potent anti-prion agents in prion infected neuronal cells and in the
      amyloid seeding assays: HS adsorb both recPrP and prions, thus sequestering them
      from the prion replication process. We interpreted our findings as highly
      relevant from an environmental point of view, as the adsorption of prions in HS
      may affect their availability and consequently hinder the environmental
      transmission of prion diseases in ruminants. 

PMID- 24937267
TI  - Decline of umami preference in aged rats.
AB  - The effects of aging on the umami sensation were compared between the preference
      and neural responses from the greater superficial petrosal nerve (GSP innervating
      the soft palate) and the chorda tympani nerve (CT innervating the fungiform
      papillae) in the Sprague Dawley rat. A two-bottle preference test revealed that
      younger rats (5-12 weeks) preferred significantly 0.001 M 5'-inosine
      monophosphate (IMP), 0.01 M mono sodium glutamate (MSG), and binary mixtures of
      0.001 M IMP+0.01 M MSG than deionized water. However, aged rats (21-22 months)
      showed no significant preference to these umami solutions compared to deionized
      water. Among the other four basic taste stimuli, there were no significant
      differences in preference between young and aged rats. Regardless of the age of
      the rat, neural responses from the GSP and CT produced robust integrated
      responses to all three umami solutions used in the two-bottle tests. These
      results indicate that the lack of preference to umami in aged rats is a central
      nervous system phenomenon and suggests that the loss of preference to umami taste
      in aged rats is caused by homeostatic changes in the brain incurred by aging.

PMID- 24937268
TI  - Microvascular network alterations in retina of subjects with cerebral small
      vessel disease.
AB  - Novel retinal imaging techniques have enabled the assessment of quantitative
      vascular parameters, which provide information on the microvasculature before the
      appearance of retinopathy signs. Advances in neuroimaging have revealed that
      cerebral microbleeds (CMB) - besides lacunar infarcts and white matter lesions
      (WML) - may be a novel marker of cerebral small vessel disease. We examine
      whether quantitative retinal vascular parameters are related to cerebral small
      vessel disease in a Chinese population. Participants from Epidemiology of
      Dementia in Singapore Study underwent comprehensive examinations, including 3
      Tesla cranial magnetic resonance imaging and retinal-photography. Retinal
      vascular parameters (caliber, tortuosity, fractal dimension) were measured from
      photographs using a semi-automated computer-assisted program. Lacunar infarcts
      and CMB were visually graded. Total brain and WML volume were obtained using a
      validated segmentation tool. A total of 261 subjects were included, of whom 36
      had lacunar infarcts, 29 had severe WML, and 83 had CMB. In age-sex-adjusted
      models, narrower retinal arteriolar caliber, wider venular caliber and smaller
      arteriolar fractal dimension were associated with presence of multiple CMB. In
      contrast, no association was found with lacunar infarcts and WML volume. After
      multivariate adjustments, associations of venular caliber, arteriolar fractal
      dimensions and arteriolar tortuosity with CMB remained statistically significant.
      In conclusion, subjects with early structural changes in retinal microvasculature
      were more likely to have CMBs, supporting hypothesis that CMB may be an early
      manifestation of cerebral small vessel disease.

PMID- 24937269
TI  - Healthy children show gender differences in correlations between nonverbal
      cognitive ability and brain activation during visual perception.
AB  - Humans perceive textual and nontextual information in visual perception, and both
      depend on language. In childhood education, students exhibit diverse perceptual
      abilities, such that some students process textual information better and some
      process nontextual information better. These predispositions involve many
      factors, including cognitive ability and learning preference. However, the
      relationship between verbal and nonverbal cognitive abilities and brain
      activation during visual perception has not yet been examined in children. We
      used functional magnetic resonance imaging to examine the relationship between
      nonverbal and verbal cognitive abilities and brain activation during nontextual
      visual perception in large numbers of children. A significant positive
      correlation was found between nonverbal cognitive abilities and brain activation
      in the right temporoparietal junction, which is thought to be related to
      attention reorienting. This significant positive correlation existed only in
      boys. These findings suggested that male brain activation differed from female
      brain activation, and that this depended on individual cognitive processes, even
      if there was no gender difference in behavioral performance. 

PMID- 24937270
TI  - QEEG indexed frontal connectivity effects of transcranial pulsed current
      stimulation (tPCS): A sham-controlled mechanistic trial.
AB  - Transcranial pulsed current stimulation (tPCS) is a non-invasive brain
      stimulation technique that employs weak, pulsed current at different frequency
      ranges, inducing electrical currents that reach cortical and subcortical
      structures. Very little is known about its effects on brain oscillations and
      functional connectivity and whether these effects are dependent on the frequency
      of stimulation. Our aim was to evaluate the effects of tPCS with different
      frequency ranges in cortical oscillations indexed by high-resolution qEEG changes
      for power and interhemispheric coherence. Thirty-eight healthy subjects were
      enrolled and received a single 20-min session of either sham or active
      stimulation with 1 Hz, 100 Hz or random frequency (1-5 Hz). We conducted an
      exploratory analysis to detect changes in mean power for theta, alpha and beta,
      and interhemispheric coherence for alpha and theta and four different sub-bands
      cognitive and non-specific adverse effects were recorded. We found that active
      stimulation with a random frequency ranging between 1 and 5 Hz is able to
      significantly increase functional connectivity for the theta and low-alpha band
      as compared to sham and active stimulation with either 1 or 100 Hz. Based on
      these findings, we discuss the possible effects of tPCS on resting functional
      connectivity for low-frequency bands in fronto-temporal areas. Future studies
      should be conducted to investigate the potential benefit of these induced changes
      in pathologic states.

PMID- 24937272
TI  - Lack of protracted behavioral abnormalities following intermittent or continuous
      chronic mild hypoxia in perinatal C57BL/6 mice.
AB  - Several prospective studies indicated perinatal hypoxia as risk factor for
      psychiatric disorders like schizophrenia. It is thought that hypoxia prior to or
      during birth may contribute to alterations leading to the protracted clinical
      manifestation during young adulthood. However, only a small fraction of children
      with a history of perinatal hypoxia develop later psychotic symptoms, therefore
      it is not known if hypoxia alone is sufficient to trigger long-term behavioral
      changes. Here we exposed C57BL/6 mice from postnatal day 3-7 (P3-P7) to two
      established paradigms of chronic mild hypoxia (10% ambient O2), intermittent and
      continuous. Subsequently, mice were analysed during young adult stages using
      several basic behavioral tests. Previous studies demonstrated severe, but only
      transient, cortical damage in these paradigms; it is not clear, if these
      reversible morphological changes are accompanied by long-term behavioral effects.
      We found that neither intermittent nor continuous perinatal hypoxia induced long
      term behavioral alterations. This may be due to the high regenerative capacity of
      the perinatal brain. Other possibilities include a potential resistance to
      perinatal hypoxia of the mouse strain used here or a level of hypoxia that was
      insufficient to trigger significant behavioral changes. Therefore, our data do
      not exclude a role of perinatal hypoxia as risk factor for psychiatric disorders.
      They rather suggest that either other, more severe hypoxic conditions like
      anoxia, or the presence of additional factors (as genetic risk factors) are
      necessary for generating long-term behavioral abnormalities. 

PMID- 24937271
TI  - Blood brain barrier is impermeable to solutes and permeable to water after
      experimental pediatric cardiac arrest.
AB  - Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological
      outcome in most survivors. Development of neuroprotective therapies is contingent
      upon understanding the permeability of intravenously delivered medications
      through the blood brain barrier (BBB). In a model of pediatric CA we sought to
      characterize BBB permeability to small and large molecular weight substances.
      Additionally, we measured the percent brain water after CA. Asphyxia of 9 min was
      induced in 16-18 day-old rats. The rats were resuscitated and the BBB
      permeability to small (sodium fluorescein and gadoteridol) and large
      (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24 h after asphyxial
      CA or sham surgery. Percent brain water was measured post-CA and in shams using
      wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1,
      4h and over the entire 24 h post-CA did not differ from shams, suggesting absence
      of BBB permeability to these solutes. Cerebral water content was increased at 3h
      post-CA vs. sham. In conclusion, after 9 min of asphyxial CA there is no BBB
      permeability over 24h to conventional small or large molecule tracers despite the
      fact that cerebral water content is increased early post-CA indicating the
      development of brain edema. Evaluation of novel therapies targeting neuronal
      death after pediatric CA should include their capacity to cross the BBB.

PMID- 24937273
TI  - Low bioavailability of silver nanoparticles presents trophic toxicity to marine
      medaka (Oryzias melastigma).
AB  - Concerns for the potential risks of silver nanoparticles (AgNPs) to aquatic
      organisms have increased. The present study investigated the trophic transfer of
      AgNPs from brine shrimp (Artemia salina) nauplii to marine medaka. We found that
      the aggregated AgNPs (20 and 80 nm) and well dispersed 80-nm AgNPs (stabilized by
      20 MUM Tween 20) could be readily accumulated by brine shrimp, while far less
      well-dispersed 20-nm AgNPs were accumulated. The assimilation efficiency (AE) of
      AgNPs in medaka fed AgNPs-contaminated brine shrimp was low (<6%), resulting in a
      low trophic transfer efficiency (0.01-0.04) after 28 days of chronic dietary
      exposure. However, such low bioavailability of dietary AgNPs could inhibit the
      whole-body Na+/K+-ATPase and superoxide dismutase (SOD) activity in the fish
      within the first 2 weeks of exposure. Significant (p<0.05, two-way ANOVA)
      inhibition occurred in the high AgNPs-contaminated brine shrimp treatment over 28
      days of chronic exposure. Furthermore, reduced growth and water content
      percentage were also observed in fish fed high dosages of AgNPs-contaminated
      brine shrimp. Our study highlighted the potential of trophically available AgNPs
      in bringing toxicity to the marine fish.

PMID- 24937274
TI  - Paneth cells.

PMID- 24937275
TI  - Lunar cycle effects on sleep and the file drawer problem.

PMID- 24937276
TI  - Human sleep and cortical reactivity are influenced by lunar phase.

PMID- 24937277
TI  - Climate-linked iceberg activity massively reduces spatial competition in
      Antarctic shallow waters.

PMID- 24937278
TI  - Neural circuit assembly: economically wired by a single cadherin.
AB  - Neurons are thought to acquire shapes and configurations consistent with the
      wiring optimization principle. A new study sheds light on the underlying
      molecular mechanisms by demonstrating that N-cadherin-mediated differential
      adhesion determines relative neurite positioning in developing columnar synaptic
      modules.

PMID- 24937279
TI  - Sleep: a biological stimulus from our nearest celestial neighbor?
AB  - Three studies have retrospectively analysed different data-sets to assess whether
      there is an effect of lunar phase upon human sleep. The results and conclusions
      differ. Until specifically designed experiments, controlling for key variables,
      are undertaken this issue will remain open. 

PMID- 24937280
TI  - Autophagy: close contact keeps out the uninvited.
AB  - In selective autophagy, autophagosomes sequester specific targets to be degraded
      in lysosomes/vacuoles. A new study now provides critical insights into the
      mechanism by which the autophagosomal membrane closely sticks to the target to
      avoid incorporating material that should not be degraded.

PMID- 24937281
TI  - Horizontal gene transfer: accidental inheritance drives adaptation.
AB  - Few facts in biology are more certain than offspring inheriting genetic material
      from their parents, but not all genes are acquired this way. A new report
      documents the horizontal transfer of a potentially adaptive gene between
      distantly related plants. 

PMID- 24937282
TI  - Evolution: how a barnacle came to parasitise a shark.
AB  - A new study on a parasitic barnacle that lives on a deep sea shark found that its
      closest living relatives are rocky shore barnacles. The findings provide insight
      into barnacle phylogeny and raise new questions about the evolution of
      parasitism. 

PMID- 24937283
TI  - Sensory biology: it takes Piezo2 to tango.
AB  - A trio of papers has resolved an outstanding controversy regarding the function
      of Merkel cells and their afferent nerve fiber partners. Merkel cells sense
      mechanical stimuli (through Piezo2), fire action potentials, and are sufficient
      to activate downstream sensory neurons.

PMID- 24937284
TI  - Development: better sleep on it, children.
AB  - A new study has identified a neural circuit that is responsible for increasing
      sleep in young fruit flies. Reduced dopamine signaling to the fan-shaped body
      during early life promotes sleep and is critical for proper brain development. 

PMID- 24937285
TI  - Genomic stability: boosting cohesion corrects CIN.
AB  - Chromosomal instability is a driving force for heterogeneity within tumours. A
      recent study shows that boosting sister chromatid cohesion corrects chromosomal
      instability in pRB-deficient cancer cells. This key finding provides an important
      lead to make tumours more susceptible to anti-cancer drugs.

PMID- 24937286
TI  - Innate lymphoid cells: of precursors and products....
AB  - Recent reports have identified committed innate lymphoid cell (ILC) precursors
      and tissue-resident ILC subsets that have unique functional attributes. Taken
      together, these studies provide a framework for understanding how distinct ILCs
      are generated during hematopoiesis and further suggest additional parallels
      between models of ILC and T helper cell differentiation. 

PMID- 24937287
TI  - Somatic mosaicism and disease.
AB  - The large number of cell divisions required to make a human body inevitably leads
      to the accumulation of somatic mutations. Such mutations cause individuals to be
      somatic mosaics. Recent advances in genomic technology now allow measurement of
      somatic diversity. Initial studies confirmed the expected high levels of somatic
      mutations within individuals. Going forward, the big questions concern the degree
      to which those somatic mutations influence disease. Theory predicts that the
      frequency of mutant cells should vary greatly between individuals. Such somatic
      mutational variability between individuals could explain much of the diversity in
      the risk of disease. But how variable is mosaicism between individuals in
      reality? What is the relation between the fraction of cells carrying a
      predisposing mutation and the risk of disease? What kinds of heritable somatic
      change lead to disease besides classical DNA mutations? What molecular processes
      connect a predisposing somatic change to disease? We know that predisposing
      somatic mutations strongly influence the onset of cancer. Likewise,
      neurodegenerative diseases may often begin from somatically mutated cells. If so,
      both neurodegeneration and cancer may be diseases of later life for which much of
      the risk may be set by early life somatic mutations.

PMID- 24937288
TI  - A colorimetric sandwich-type assay for sensitive thrombin detection based on
      enzyme-linked aptamer assay.
AB  - A colorimetric sandwich-type assay based on enzyme-linked aptamer assay has been
      developed for the fast and sensitive detection of as low as 25 fM of thrombin
      with high linearity. Aptamer-immobilized glass was used to capture the target
      analyte, whereas a second aptamer, functionalized with horseradish peroxidase
      (HRP), was employed for the conventional 3,5,3',5'-tetramethylbenzidine (TMB)
      based colorimetric detection. Without the troublesome antibody requirement of the
      conventional enzyme-linked immunosorbent assay (ELISA), as low as 25 fM of
      thrombin could be rapidly and reproducibly detected. This assay has superior, or
      at least equal, recovery and accuracy to that of conventional antibody-based
      ELISA.

PMID- 24937289
TI  - Interprofessional dedicated education unit: an academic practice partnership.

PMID- 24937290
TI  - Faculty-facilitated remediation: a model to transform at-risk students.
AB  - A remediation program was implemented during the semester break in an associate
      degree nursing program to increase the pass rate on the NCLEX-RN of at-risk
      students in a targeted medical-surgical nursing course. Through the use of a
      course management system and an adaptive quizzing program, participants were
      facilitated to take a more active role in their learning. Faculty mentored
      students and witnessed a transformation in participants through graduation.
      Ultimately, success of these at-risk students in passing the NCLEX-RN helped
      maintain this nursing program's pass rate. 

PMID- 24937291
TI  - Web conferencing in online classrooms.
AB  - Web conferencing is a promising tool for online education. A well-developed
      teaching strategy can lead to effective use of this technology to create a sense
      of community, engage students, and promote academic integrity in online courses.
      This article presents strategies for integrating Web conferencing into online
      nursing courses. 

PMID- 24937292
TI  - Evaluating the use of a simulated electronic health record and online drug
      reference in a case study to enhance nursing students' understanding of
      pharmacologic concepts and resources.
AB  - Nursing students should learn to navigate the complexities of the healthcare
      arena, such as integrating use of electronic health records (EHRs) and online
      drug references into patient care. Using a simulated EHR in a nursing
      pharmacology course allowed students to interact with these technologies while
      learning and applying pharmacologic concepts to a case study. The authors discuss
      how they created and facilitated such a case study, as well as students'
      outcomes. 

PMID- 24937293
TI  - Mobile applications in nursing education and practice.
AB  - Students in an RN-BSN completion program capstone course investigated and
      critically evaluated mobile medical applications using an information literacy
      conceptual framework. Students also analyzed their potential usefulness as a
      resource in nursing practice. Student evaluations focused on usability and
      applicability when recommending the use of mobile applications as a point-of-care
      reference tools. This pilot assignment offers an innovative teaching strategy for
      integrating 1 aspect of informatics instruction into the nursing curriculum. 

PMID- 24937294
TI  - Academic-practice collaboration in nursing education: service-learning for injury
      prevention.
AB  - Teams of senior-level baccalaureate nursing students at a private, urban
      university complete a population-focused public health nursing practicum through
      service-learning partnerships. Recently, students collaborated with local service
      agencies for Safe Communities America, a program of the National Safety Council
      in affiliation with the World Health Organization. This article describes the
      student-led process of community assessment, followed by systematic planning,
      implementation, and evaluation of evidence-based interventions to advance
      prescription drug overdose/poisoning prevention efforts in the community. 

PMID- 24937295
TI  - Campus Clinical: simulation-based curriculum designed to meet clinical course
      learning outcomes.
AB  - Campus Clinical is a simulation-based curriculum designed to meet the challenge
      of decreasing clinical spaces in maternal-child units. The curriculum framework
      is situated in a constructivist, experiential learning context, integrating
      Chickering and Gamson's principles for good practice in education. This
      innovative approach to meeting clinical course learning outcomes is transferable
      to a variety of settings. 

PMID- 24937296
TI  - Teaching quality and safety in nursing programs.

PMID- 24937297
TI  - Graduate forensic nursing education: how to better educate nurses to care for
      this patient population.
AB  - Nurses are often the first healthcare contact for those affected by violence.
      Despite the impact of violence on healthcare across specialties and ages,
      forensic nursing content is limited in undergraduate and graduate curricula. The
      purpose of this article is to provide background on forensic nursing and present
      a model of a graduate forensic nursing program that can be used as a curriculum
      guide. 

PMID- 24937298
TI  - Developing an academic and American Indian tribal partnership in education: a
      model of community health nursing clinical education.
AB  - American Indian tribes shoulder a heavy burden in health inequities and recognize
      the value of partnerships with academic institutions. This article describes a
      unique education model developed through a partnership between a school of
      nursing and 2 Pacific Northwest tribes to provide clinical education for
      students. Over 3 years, students and faculty worked with 2 tribal communities to
      design research and implement education programs. 

PMID- 24937299
TI  - Use of student photography to explore nursing.

PMID- 24937300
TI  - A comparative study of cultural competence curricula in baccalaureate nursing
      programs.
AB  - This study evaluated the cultural competence and cultural confidence (self
      efficacy) levels of baccalaureate nursing students in 3 types of programs: those
      with integrated cultural content, those with a required nonnursing culture
      course, and those with a culture course in nursing. A sample of 759 students
      participated. Only the students in the nursing culture course program reached a
      level of cultural competence. Cultural competence and confidence increased
      significantly from freshman to junior year in all 3 programs. 

PMID- 24937301
TI  - Creative classroom strategies for teaching nursing research.
AB  - Faculty are constantly challenged to find interesting classroom activities to
      teach nursing content and engage students in learning. Nursing students and
      graduates need to use research skills and evidence-based practice as part of
      their professional care. Finding creative and engaging ways to teach this
      material in undergraduate nursing programs are essential. This article outlines
      several successful strategies to engage nursing students in research content in
      the time and space constraints of the classroom. 

PMID- 24937302
TI  - Effectiveness of the clinical teaching associate model to improve clinical
      learning outcomes: a randomized controlled trial.
AB  - This study examined the effectiveness of the clinical teaching associate (CTA)
      model to improve clinical learning outcomes in nursing students. Students were
      randomly allocated to either the CTA (n = 28) or traditional training group (n =
      32), and their clinical knowledge, skills, and satisfaction with the learning
      experience were assessed and compared. The results showed that the CTA model was
      equally effective in improving clinical knowledge, skills, and satisfaction of
      nursing students. 

PMID- 24937303
TI  - Response of mice and ferrets to a monovalent influenza A (H7N9) split vaccine.
AB  - In early spring 2013, the emergence of the influenza A (H7N9) virus in humans in
      Eastern China raised concerns of a new influenza pandemic. Development of a safe
      and effective H7N9 influenza vaccine is urgently needed. To this end, we first
      synthesized the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza
      A (H7N9) virus A/AnHui/1/2013. Using reverse genetics, we rescued a reassortant
      virus (H7N9/PR8) that contained the HA and NA genes from wild-type H7N9 and six
      genes encoding internal proteins from the A/Puerto Rico/8/34 (PR8) virus. Next,
      the pathogenicity of the reassortant virus was evaluated both in vivo and in
      vitro. We found that the virus was non-pathogenic in mice and was stable after
      serial passaging in eggs. Furthermore, we found that a monovalent influenza A
      (H7N9) split vaccine prepared from the virus was immunogenic in mice and ferrets.
      When given intramuscularly, the vaccine (two doses of at least 15-ug) completely
      protected mice from normally lethal wild-type H7N9 virus challenge. In summary,
      our H7N9 vaccine, developed over a short time, is a potential candidate for
      further clinical evaluation and human use. 

PMID- 24937304
TI  - Non melanoma skin cancer and subsequent cancer risk.
AB  - INTRODUCTION: Several studies have shown an increased risk of cancer after non
      melanoma skin cancers (NMSC) but the individual risk factors underlying this risk
      have not been elucidated, especially in relation to sun exposure and skin
      sensitivity to sunlight. PURPOSE: The aim of this study was to examine the
      individual risk factors associated with the development of subsequent cancers
      after non melanoma skin cancer. METHODS: Participants in the population-based New
      Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent
      cancers were identified via linkage with the state cancer registry. Deaths were
      identified via state and national death records. A Cox proportional hazard model
      was used to estimate risk of subsequent malignancies in NMSC patients versus
      controls and to assess the potential confounding effects of multiple risk factors
      on this risk. RESULTS: Among 3584 participants, risk of a subsequent cancer
      (other than NMSC) was higher after basal cell carcinoma (BCC) (adjusted HR 1.40
      [95% CI 1.15, 1.71]) than squamous cell carcinoma (SCC) (adjusted HR 1.18 [95% CI
      0.95, 1.46]) compared to controls (adjusted for age, sex and current cigarette
      smoking). After SCC, risk was higher among those diagnosed before age 60 (HR 1.96
      [95% CI 1.24, 3.12]). An over 3-fold risk of melanoma after SCC (HR 3.62; 95% CI
      1.85, 7.11) and BCC (HR 3.28; 95% CI 1.66, 6.51) was observed, even after further
      adjustment for sun exposure-related factors and family history of skin cancer. In
      men, prostate cancer incidence was higher after BCC compared to controls (HR
      1.64; 95% CI 1.10, 2.46). CONCLUSIONS: Our population-based study indicates an
      increased cancer risk after NMSC that cannot be fully explained by known cancer
      risk factors.

PMID- 24937305
TI  - Red blood cell transfusion and mortality in trauma patients: risk-stratified
      analysis of an observational study.
AB  - BACKGROUND: Haemorrhage is a common cause of death in trauma patients. Although
      transfusions are extensively used in the care of bleeding trauma patients, there
      is uncertainty about the balance of risks and benefits and how this balance
      depends on the baseline risk of death. Our objective was to evaluate the
      association of red blood cell (RBC) transfusion with mortality according to the
      predicted risk of death. METHODS AND FINDINGS: A secondary analysis of the CRASH
      2 trial (which originally evaluated the effect of tranexamic acid on mortality in
      trauma patients) was conducted. The trial included 20,127 trauma patients with
      significant bleeding from 274 hospitals in 40 countries. We evaluated the
      association of RBC transfusion with mortality in four strata of predicted risk of
      death: <6%, 6%-20%, 21%-50%, and >50%. For this analysis the exposure considered
      was RBC transfusion, and the main outcome was death from all causes at 28 days. A
      total of 10,227 patients (50.8%) received at least one transfusion. We found
      strong evidence that the association of transfusion with all-cause mortality
      varied according to the predicted risk of death (p-value for interaction
      <0.0001). Transfusion was associated with an increase in all-cause mortality
      among patients with <6% and 6%-20% predicted risk of death (odds ratio [OR] 5.40,
      95% CI 4.08-7.13, p<0.0001, and OR 2.31, 95% CI 1.96-2.73, p<0.0001,
      respectively), but with a decrease in all-cause mortality in patients with >50%
      predicted risk of death (OR 0.59, 95% CI 0.47-0.74, p<0.0001). Transfusion was
      associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95%
      CI 2.05-3.24, p<0.0001). The risk associated with RBC transfusion was
      significantly increased for all the predicted risk of death categories, but the
      relative increase was higher for those with the lowest (<6%) predicted risk of
      death (p-value for interaction <0.0001). As this was an observational study, the
      results could have been affected by different types of confounding. In addition,
      we could not consider haemoglobin in our analysis. In sensitivity analyses,
      excluding patients who died early; conducting propensity score analysis adjusting
      by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for
      country produced results that were similar. CONCLUSIONS: The association of
      transfusion with all-cause mortality appears to vary according to the predicted
      risk of death. Transfusion may reduce mortality in patients at high risk of death
      but increase mortality in those at low risk. The effect of transfusion in low
      risk patients should be further tested in a randomised trial. TRIAL REGISTRATION:
      www.ClinicalTrials.gov NCT01746953.

PMID- 24937306
TI  - TC1(C8orf4) regulates hematopoietic stem/progenitor cells and hematopoiesis.
AB  - Hematopoiesis is a complex process requiring multiple regulators for
      hematopoietic stem/progenitor cells (HSPC) and differentiation to multi-lineage
      blood cells. TC1(C8orf4) is implicated in cancers, hematological malignancies and
      inflammatory activation. Here, we report that Tc1 regulates hematopoiesis in
      mice. Myeloid and lymphoid cells are increased markedly in peripheral blood of
      Tc1-deleted mice compared to wild type controls. Red blood cells are small-sized
      but increased in number. The bone marrow of Tc1-/- mice is normocellular
      histologically. However, Lin-Sca-1+c-Kit+ (LSK) cells are expanded in Tc1-/- mice
      compared to wild type controls. The expanded population mostly consists of CD150
      CD48+ cells, suggesting the expansion of lineage-restricted hematopoietic
      progenitor cells. Colony forming units (CFU) are increased in Tc1-/- mice bone
      marrow cells compared to controls. In wild type mice bone marrow, Tc1 is
      expressed in a limited population of HSPC but not in differentiated cells. Major
      myeloid transcriptional regulators such as Pu.1 and Cebpalpha are not up
      regulated in Tc1-/- mice bone marrow. Our findings indicate that TC1 is a novel
      hematopoietic regulator. The mechanisms of TC1-dependent HSPC regulation and
      lineage determination are unknown. 

PMID- 24937307
TI  - Body mass index, waist circumference, body adiposity index, and risk for type 2
      diabetes in two populations in Brazil: general and Amerindian.
AB  - OBJECTIVE: The use of the anthropometric indices of adiposity, especially body
      mass index and waist circumference in the prediction of diabetes mellitus has
      been widely explored. Recently, a new body composition index, the body adiposity
      index was proposed. The aim of this study was to compare the effectiveness of
      body mass index, waist circumference, and body adiposity index in the risk
      assessment for type 2 diabetes mellitus. DESIGN AND METHODS: A total of 1,572
      individuals from the general population of Vitoria City, Brazil and 620
      Amerindians from the Aracruz Indian Reserve, Brazil were randomly selected. BMI,
      waist circumference, and BAI were determined according to a standard protocol.
      Type 2 diabetes mellitus was diagnosed by the presence of fasting glucose >=126
      mg/dL or by the use of antidiabetic drugs. RESULTS: The area under the curve was
      similar for all anthropometric indices tested in the Amerindian population, but
      with very different sensitivities or specificities. In women from the general
      population, the area under the curve of waist circumference was significantly
      higher than that of the body adiposity index. Regarding risk assessment for type
      2 diabetes mellitus, the body adiposity index was a better risk predictor than
      body mass index and waist circumference in the Amerindian population and was the
      index with highest odds ratio for type 2 diabetes mellitus in men from the
      general population, while in women from the general population waist
      circumference was the best risk predictor. CONCLUSION: Body adiposity index was
      the best risk predictor for type 2 diabetes mellitus in the Amerindian population
      and men from the general population. Our data suggest that the body adiposity
      index is a useful tool for the risk assessment of type 2 diabetes mellitus in
      admixture populations.

PMID- 24937308
TI  - Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity: relevance
      to global HIV vaccine design.
AB  - OBJECTIVE: The objective of this study is to determine the breadth of HIV-1 Env
      specific antibody-dependent cellular cytotoxicity (ADCC) in HIV controllers and
      HIV progressors with a view to design globally relevant HIV vaccines. DESIGN: The
      breadth of ADCC towards four major HIV-1 Env subtypes was measured in vitro for
      11 HIV controllers and 11 HIV progressors. METHODS: Plasma from 11 HIV
      controllers (including long-term slow progressors, viremic controllers, elite
      controller and posttreatment controller) and 11 HIV progressors, mostly infected
      with HIV-1 subtype B, was analysed for ADCC responses. ADCC assays were performed
      against 10 HIV-1 gp120 and 8 gp140 proteins from four major HIV-1 subtypes (A, B,
      C and E) and 3 glycosylation-mutant gp140 proteins. RESULTS: ADCC-mediated
      natural killer cell activation was significantly broader (P = 0.02) and of higher
      magnitude (P < 0.001) in HIV controllers than in HIV progressors. HIV controllers
      also showed significantly higher magnitude of ADCC-mediated killing of Env-coated
      target cells than HIV progressors to both HIV-1 subtype B and the heterologous
      subtype E gp140 (P = 0.001). We found good ADCC reactivity to subtype B and E
      Envs, less cross-reactivity to subtype A and minimal cross-reactivity to subtype
      C Envs. Glycosylation-dependent ADCC epitopes comprise a significant proportion
      of the total Env-specific ADCC response, as evident from the reduction in ADCC to
      nonglycosylated form of HIV-1 gp140 (P = 0.004). CONCLUSION: HIV controllers have
      robust ADCC responses that recognize a broad range of HIV-1 Env. Glycosylation of
      Env was found to be important for recognition of ADCC epitopes. Identifying
      conserved ADCC epitopes will assist in designing globally relevant ADCC-based HIV
      vaccines.

PMID- 24937309
TI  - HIV infection and incidence of ischemic stroke.
AB  - OBJECTIVE: To determine the association of HIV infection and immunodeficiency
      with incidence of ischemic stroke. DESIGN: Cohort study of HIV-positive and
      matched HIV-negative adult Kaiser Permanente Northern and Southern California
      (KPNC and KPSC, respectively) members during 1996-2011 (KPNC) or 2000-2011
      (KPSC). METHODS: We used Poisson models to obtain rate ratios for incident
      ischemic stroke associated with HIV infection, both overall and stratified by CD4
      cell counts (cells/MUl) and HIV RNA copies (copies/ml), with HIV-negative
      individuals as the reference group. We also obtained rate ratios for risk factors
      in the HIV-positive subset. RESULTS: Among 24,768 HIV-positive and 257,600 HIV
      negative individuals, the ischemic stroke rate per 100,000 person-years was 125
      (n = 151 events) for HIV-positive and 74 (n = 1128 events) for HIV-negative
      individuals, with an adjusted rate ratio of 1.4 [95% confidence interval (CI) 1.2
      1.7). Compared with HIV-negative individuals, HIV-positive individuals with
      recent CD4 cell counts of 500 cells/MUl at least (rate ratio 1.0, 95% CI 0.8-1.4)
      or recent HIV RNA less than 500 copies/ml (rate ratio 1.1, 95% CI 0.9-1.4) had no
      excess risk of ischemic stroke, with similar results for HIV-positive individuals
      with nadir CD4 cell counts of 500 cells/MUl at least (rate ratio 1.4, 95% CI 0.8
      2.2) or 200-499 cells/MUl (rate ratio 1.2, 95% CI 0.9-1.5). Among HIV-positive
      individuals only, recent CD4 cell count less than 200 cells/MUl (rate ratio 2.5,
      95% CI 1.3-4.6) was associated with an increased risk of ischemic stroke after
      adjustment for recent HIV RNA and nadir CD4 cell count, whereas recent HIV RNA
      and nadir CD4 were not independent risk factors. CONCLUSION: Ischemic stroke
      incidence in HIV-positive individuals with high CD4 cell count or low HIV RNA is
      similar to that of HIV-negative individuals.

PMID- 24937310
TI  - Generalized estimating equation approach for analyzing the effects of metal
      derived products on survival and hatching of zebrafish embryos.
AB  - Zebrafish embryos are widely used as a model to monitor the effect of chemicals
      on their survival and hatching at different time epochs. This experimental design
      generates longitudinal data in which the observations for a given subject are
      correlated and they are statistically independent across the subjects. This
      particular nature of the observations suggests the use of generalized estimating
      equation (GEE) methodology for performing meaningful statistical analysis.
      However, it has been observed that the researchers working in this area have been
      routinely employing statistical methodologies such as analysis of variance
      (ANOVA) if the data are continuous and logit or probit models if the data are
      discrete. In our opinion, it is grossly incorrect to use these methods as they do
      not take into account the correlation structure mentioned above. The sole purpose
      of this article is to bring out this serious flaw clearly to the attention of the
      researchers. For illustration, we have studied the effects of two Ayurvedic
      bhasmas-Tamra bhasma and Suwarnamakshik bhasma-on survival and hatching of
      zebrafish embryos over certain time duration. The statistical analysis using GEE
      reveals a weak promotional effect of Suwarnamakshik bhasma and an inhibitory
      effect of Tamra bhasma on hatching.

PMID- 24937311
TI  - Use of mode of action data to inform a dose-response assessment for bladder
      cancer following exposure to inorganic arsenic.
AB  - In the recent National Research Council report on conducting a dose-response
      assessment for inorganic arsenic, the committee remarked that mode of action data
      should be used, to the extent possible, to extrapolate below the observed range
      for epidemiological studies to inform the shape of the dose-response curve.
      Recent in vitro mode of action studies focused on understanding the development
      of bladder cancer following exposure to inorganic arsenic provide data to inform
      the dose-response curve. These in vitro data, combined with results of bladder
      cancer epidemiology studies, inform the dose-response curve in the low-dose
      region, and include values for both pharmacokinetic and pharmacodynamic
      variability. Integration of these data provides evidence of a range of
      concentrations of arsenic for which no effect on the bladder would be expected.
      Specifically, integration of these results suggest that arsenic exposures in the
      range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes
      leading to key events in the development of cancer or noncancer effects in
      bladder tissue. These findings are consistent with the lack of evidence for
      bladder cancer following chronic ingestion of arsenic water concentrations <100
      ppb in epidemiological studies.

PMID- 24937314
TI  - Photoactivatable glycopolymers for the proteome-wide identification of fucose
      alpha(1-2)-galactose binding proteins.
AB  - Although fucose-alpha(1-2)-galactose (Fucalpha(1-2)Gal)-containing glycans have
      been implicated in cognitive processes such as learning and memory, their precise
      molecular mechanisms are poorly understood. Here we employed the use of
      multivalent glycopolymers to enable the first proteome-wide identification of
      weak affinity, low abundance Fucalpha(1-2)Gal glycan-binding proteins (GBPs).
      Biotin-terminated glycopolymers containing photoactivatable cross-linking groups
      were designed to capture and enrich GBPs from rat brain lysates. Candidate
      proteins were tested for their ability to bind Fucalpha(1-2)Gal, and the
      functional significance of the interaction was investigated for the synaptic
      vesicle protein SV2a using a knockout mouse system. The results suggest a role
      for SV2a-Fucalpha(1-2)Gal interactions in SV2a trafficking and synaptic vesicle
      recycling. More broadly, our studies outline a general chemical approach for the
      systems-level discovery of novel GBPs. 

PMID- 24937315
TI  - Adsorption of tetracycline from aqueous solutions onto multi-walled carbon
      nanotubes with different oxygen contents.
AB  - Oxidized multi-walled carbon nanotubes (MWCNTs) with different oxygen contents
      were investigated for the adsorption of tetracycline (TC) from aqueous solutions.
      As the surface oxygen content of the MWCNTs increased, the maximum adsorption
      capacity and adsorption coefficient of TC increased to the largest values and
      then decreased. The relation can be attributed to the interplay between the
      nanotubes' dispersibility and the water cluster formation upon TC adsorption. The
      overall adsorption kinetics of TC onto CNTs-3.2%O might be dependent on both
      intra-particle diffusion and boundary layer diffusion. The maximum adsorption
      capacity of TC on CNTs-3.2%O was achieved in the pH range of 3.3-8.0 due to
      formation of water clusters or H-bonds. Furthermore, the presence of Cu(2+) could
      significantly enhanced TC adsorption at pH of 5.0. However, the solution ionic
      strength did not exhibit remarkable effect on TC adsorption. In addition, when pH
      is beyond the range (3.3-8.0), the electrostatic interactions caused the decrease
      of TC adsorption capacity. Our results indicate that surface properties and
      aqueous solution chemistry play important roles in TC adsorption on MWCNTs. 

PMID- 24937316
TI  - An unusual abscisic acid and gibberellic acid synergism increases somatic
      embryogenesis, facilitates its genetic analysis and improves transformation in
      Medicago truncatula.
AB  - Somatic embryogenesis (SE) can be readily induced in leaf explants of the
      Jemalong 2HA genotype of the model legume Medicago truncatula by auxin and
      cytokinin, but rarely in wild-type Jemalong. Gibberellic acid (GA), a hormone not
      included in the medium, appears to act in Arabidopsis as a repressor of the
      embryonic state such that low ABA (abscisic acid): GA ratios will inhibit SE. It
      was important to evaluate the GA effect in M. truncatula in order to formulate
      generic SE mechanisms, given the Arabidopsis information. It was surprising to
      find that low ABA:GA ratios in M. truncatula acted synergistically to stimulate
      SE. The unusual synergism between GA and ABA in inducing SE has utility in
      improving SE for regeneration and transformation in M. truncatula. Expression of
      genes previously shown to be important in M. truncatula SE was not increased. In
      investigating genes previously studied in GA investigations of Arabidopsis SE,
      there was increased expression of GA2ox and decreased expression of PICKLE, a
      negative regulator of SE in Arabidopsis. We suggest that in M. truncatula there
      are different ABA:GA ratios required for down-regulating the PICKLE gene, a
      repressor of the embryonic state. In M. truncatula it is a low ABA:GA ratio while
      in Arabidopsis it is a high ABA:GA ratio. In different species the expression of
      key genes is probably related to differences in how the hormone networks optimise
      their expression. 

PMID- 24937317
TI  - Functional duality of the cell wall.
AB  - The polysaccharide cell wall is the extracellular armour of the fungal cell.
      Although essential in the protection of the fungal cell against aggressive
      external stresses, the biosynthesis of the polysaccharide core is poorly
      understood. For a long time it was considered that this cell wall skeleton was a
      fixed structure whose role was only to be sensed as non-self by the host and
      consequently trigger the defence response. It is now known that the cell wall
      polysaccharide composition and localization continuously change to adapt to their
      environment and that these modifications help the fungus to escape from the
      immune system. Moreover, cell wall polysaccharides could function as true
      virulence factors. 

PMID- 24937318
TI  - Nocturnal asthma and the importance of race/ethnicity and genetic ancestry.
AB  - RATIONALE: Nocturnal asthma is a common presentation and is associated with a
      more severe form of the disease. However, there are few epidemiologic studies of
      nocturnal asthma, particularly in minority populations. OBJECTIVES: To identify
      factors associated with nocturnal asthma, including the contribution of self
      identified race/ethnicity and genetic ancestry. METHODS: The analysis included
      individuals from the Study for Asthma Phenotypes and Pharmacogenomic Interactions
      by Race-ethnicity (SAPPHIRE) cohort. Nocturnal asthma symptoms were assessed by
      questionnaire. Genome-wide genotype data were used to estimate genetic ancestry
      in a subset of African American participants. Logistic regression was used
      evaluate the association of various factors with nocturnal asthma, such as self
      identified race/ethnicity and genetic ancestry. MEASUREMENT AND MAIN RESULTS: The
      study comprised 3,380 African American and 1,818 European Americans individuals
      with asthma. After adjusting for other potential explanatory variables, including
      controller medication use, African Americans were more than twice as likely (odds
      ratio, 2.56; 95% confidence interval, 2.24-2.93) to report nocturnal asthma when
      compared with European American individuals. Among the subset of African American
      participants with genome-wide genotype data (n = 1,040), estimated proportion of
      African ancestry was also associated with an increased risk of nocturnal asthma
      (P = 0.007). Differences in lung function explained a small, but statistically
      significant (P = 0.02), proportion of the relationship between genetic ancestry
      and nocturnal asthma symptoms. CONCLUSIONS: Both self-identified race/ethnicity
      and African ancestry appear to be independent predictors of nocturnal asthma. The
      mechanism by which genetic ancestry contributes to population-level differences
      in nocturnal asthma appears to be largely independent of lung function.

PMID- 24937320
TI  - Intensification of the meridional temperature gradient in the Great Barrier Reef
      following the Last Glacial Maximum.
AB  - Tropical south-western Pacific temperatures are of vital importance to the Great
      Barrier Reef (GBR), but the role of sea surface temperatures (SSTs) in the growth
      of the GBR since the Last Glacial Maximum remains largely unknown. Here we
      present records of Sr/Ca and delta(18)O for Last Glacial Maximum and deglacial
      corals that show a considerably steeper meridional SST gradient than the present
      day in the central GBR. We find a 1-2  degrees C larger temperature decrease
      between 17 degrees  and 20 degrees S about 20,000 to 13,000 years ago. The result
      is best explained by the northward expansion of cooler subtropical waters due to
      a weakening of the South Pacific gyre and East Australian Current. Our findings
      indicate that the GBR experienced substantial meridional temperature change
      during the last deglaciation, and serve to explain anomalous deglacial drying of
      northeastern Australia. Overall, the GBR developed through significant SST change
      and may be more resilient than previously thought. 

PMID- 24937319
TI  - Common mental disorders associated with tuberculosis: a matched case-control
      study.
AB  - INTRODUCTION: Despite the availability of treatment and a vaccine, tuberculosis
      continues to be a public health problem worldwide. Mental disorders might
      contribute to the burden of the disease. OBJECTIVE: The objective of this study
      was to investigate the association between common mental disorders and
      tuberculosis. METHODS: A matched case-control study was conducted. The study
      population included symptomatic respiratory patients who attended three referral
      hospitals and six community clinics in the city of Salvador, Brazil. A doctor's
      diagnosis defined potential cases and controls. Cases were newly diagnosed
      tuberculosis cases, and controls were symptomatic respiratory patients for whom
      tuberculosis was excluded as a diagnosis by the attending physician. Cases and
      controls were ascertained in the same clinic. Data collection occurred between
      August 2008 and April 2010. The study instruments included a structured
      interview, a self-reporting questionnaire for the identification of common mental
      disorders, and a questionnaire for alcoholism. An univariate analysis included
      descriptive procedures (with chi-square statistics), and a multivariate analysis
      used conditional logistic regression. RESULTS: The mean age of the cases was 38
      years, and 61% of the cases were males. After adjusting for potential
      confounders, the odds of tuberculosis were significantly higher in patients
      diagnosed with a common mental disorder (OR: 1.34; 95% CI 1.05-1.70). CONCLUSION:
      There appears to be a positive and independent association between common mental
      disorders and tuberculosis; further epidemiological studies are required to
      increase our understanding of the possible biological and social mechanisms
      responsible for this association. Independent of the direction of the
      association, this finding has implications for the provision of care for mental
      disorders and for tuberculosis.

PMID- 24937321
TI  - Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal
      antibody, in cynomolgus monkeys: relevance for human safety.
AB  - Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody
      (MAb) targeting GM-CSF receptor alpha which is currently being developed for the
      treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid
      arthritis (RA) through the activation, differentiation, and survival of
      macrophages and neutrophils. To support clinical development, the nonclinical
      safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys
      as the pharmacologically relevant species. Comprehensive toxicity parameters were
      assessed in each study, and treatment duration ranged from 4 to 26weeks.
      Mavrilimumab has an acceptable safety profile in monkeys with no changes in any
      parameters other than microscopic findings in lung. In several studies, minimal
      accumulation of foamy alveolar macrophages was observed. This finding was only
      seen in studies of at least 11weeks duration, was reversible following a dose
      free recovery period and was considered non-adverse. At higher dose levels
      (>=30mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign
      material, cholesterol clefts, and granulomatous inflammation was also observed in
      a few animals and was considered adverse. The dose- and time-related accumulation
      of foamy macrophages in lung following exposure to mavrilimumab observed in
      several NHP studies was expected based upon the known role of GM-CSFRalpha
      signaling in the function of alveolar macrophages. Overall, a clean no-observed
      adverse-effect-level (NOAEL) without any effects in lung was established and
      provided adequate clinical safety margins. In clinical studies in RA patients,
      mavrilimumab has demonstrated good clinical activity with adequate safety to
      support further clinical development. A Phase 2b study of mavrilimumab in
      subjects with RA is in progress. 

PMID- 24937322
TI  - Chronic infusion of lisinopril into hypothalamic paraventricular nucleus
      modulates cytokines and attenuates oxidative stress in rostral ventrolateral
      medulla in hypertension.
AB  - The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla
      (RVLM) play a critical role in the generation and maintenance of sympathetic
      nerve activity. The renin-angiotensin system (RAS) in the brain is involved in
      the pathogenesis of hypertension. This study was designed to determine whether
      inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates
      cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the
      blood pressure and sympathetic activity in renovascular hypertensive rats.
      Renovascular hypertension was induced in male Sprague-Dawley rats by the two
      kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral
      PVN infusion with ACE inhibitor lisinopril (LSP, 10MUg/h) or vehicle via osmotic
      minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve
      activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly
      increased in renovascular hypertensive rats. The renovascular hypertensive rats
      also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL
      10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the
      subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in
      hypertensive rats. PVN treatment with LSP attenuated those changes occurring in
      renovascular hypertensive rats. Our findings suggest that the beneficial effects
      of ACE inhibition in the PVN in renovascular hypertension are partly due to
      modulation cytokines and attenuation oxidative stress in the RVLM. 

PMID- 24937323
TI  - Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK
      pathway.
AB  - Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are
      well documented; however, dermal toxicity is not yet explored. The effect of
      topical application of DON to mice was studied using markers of skin
      proliferation, inflammation and tumor promotion. Single topical application of
      DON (84-672nmol/mouse) significantly enhanced dermal hyperplasia and skin edema.
      DON (336 and 672nmol) caused significant enhancement in [(3)H]-thymidine uptake
      in DNA along with increased myeloperoxidase and ornithine decarboxylase
      activities, suggesting tissue inflammation and cell proliferation. Furthermore,
      DON (168nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt,
      ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription
      factors, c-fos, c-jun and NF-kappaB along with phosphorylation of IkBalpha.
      Enhanced phosphorylation of NF-kappaB by DON caused over expression of target
      proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application
      of DMBA followed by twice weekly application of DON (84 and 168nmol) showed no
      tumorigenesis after 24weeks, however, histopathological studies suggested
      hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly,
      intestine was also found to be affected as enlarged Peyer's patches were
      observed, suggesting inflammatory effects which were supported by elevation of
      inflammatory cytokines after 24weeks of topical application of DON. These results
      suggest that DON induced cell proliferation in mouse skin is through the
      activation of MAPK signaling pathway involving transcription factors NFkappaB and
      AP-1, further leading to transcriptional activation of downstream target proteins
      c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its
      inflammatory potential. 

PMID- 24937324
TI  - Social and socio-demographic neighborhood effects on adolescent alcohol use: a
      systematic review of multi-level studies.
AB  - There is growing interest in the role of the neighborhood environment on
      adolescent alcohol use. Multi-level designs are ideally suited to this
      investigation due to their ability to examine area-level effects over and above
      the effects due to neighborhood composition. To date, most research in this area
      has focused on the physical availability of alcohol in the neighborhood. We
      reviewed the multi-level evidence on neighborhood-level risk and protective
      factors which influence adolescent alcohol use, excluding studies which assessed
      the impact of neighborhood-level alcohol availability and advertising. Systematic
      searches in Medline, EMBASE, CINAHL Plus, PsycINFO, Sociological Abstracts and
      SCOPUS identified 23 studies, examining 11 different neighborhood-level
      exposures. The majority of studies found no associations with residential
      mobility, neighborhood disorder or crime, employment or job availability,
      neighborhood attitudes to drinking, social capital and collective efficacy. For
      studies examining neighborhood-level socio-economic disadvantage mixed results
      were found. High levels of both adult and adolescent alcohol use in the community
      appeared to be associated with alcohol use whilst protective effects were found
      for enforcement of liquor laws. Methodological limitations within studies were
      evident. The dearth of high-quality, multi-level studies indicate that further
      research is required to inform the development of multi-faceted place-based
      policy and preventative interventions to reduce adolescent alcohol use. Future
      studies should consider the neighborhood context from the outset of study design
      and identify the individual-level control variables to adequately isolate
      neighborhood effects. Inclusion of moderation and mediation analyses would
      greatly contribute towards the understanding of causal pathways of neighborhood
      effects. 

PMID- 24937325
TI  - Social networks and the probability of having a regular family doctor.
AB  - Social supports have been shown to affect health in a variety of ways. This paper
      explores a hitherto ignored avenue linking social supports to health, namely
      through their influence on having a regular family doctor. We examine the role
      played by social supports in helping to explain why a significant portion of the
      Canadian population does not have a regular family doctor even though primary
      care is fully covered by the public insurer and when having a regular physician
      is associated with better care and with access to specialists. Five Canadian
      Community Health Surveys spanning 2001 to 2010 (n = 13,872 to n = 30,814) are
      employed, containing information on three measures of social support: sense of
      belonging to the local community, how often an individual has someone to confide
      in, and number of close friends and relatives. We find evidence of a positive
      link between social supports, especially sense of belonging, and having a regular
      doctor. Our results suggest that the benefits associated with policies geared
      towards community development and strengthening neighborhoods may also include
      facilitating access to primary-care physicians and, importantly, improving the
      matching of patients with regular family doctors. 

PMID- 24937326
TI  - Cannabis depenalisation, drug consumption and crime - evidence from the 2004
      cannabis declassification in the UK.
AB  - This paper investigates the link between cannabis depenalisation and crime using
      individual-level panel data for England and Wales from 2003 to 2006. We exploit
      the declassification of cannabis in the UK in 2004 as a natural experiment.
      Specifically, we use the fact that the declassification changed expected
      punishments differently in various age groups due to thresholds in British
      criminal law and employ a difference-in-differences type design using data from
      the longitudinal version of the Offending, Crime and Justice Survey. Our findings
      suggest essentially no increases in either cannabis consumption, consumption of
      other drugs, crime and other forms of risky behaviour. 

PMID- 24937327
TI  - Asthma and child behavioral skills: does family socioeconomic status matter?
AB  - Asthma is associated with poorer behavioral and psychological outcomes in
      children, yet little is known about whether and how the social stratification
      process affects the impacts of asthma on children's outcomes. Using data from the
      Early Childhood Longitudinal Study-Birth Cohort, this study considered the role
      of socioeconomic status in shaping the developmental consequences of children's
      asthma. Results showed that asthma was negatively associated with attention and
      social competence and positively associated with externalizing problem behaviors
      for children with low-educated mothers and children who lived in poor households.
      However, the adverse consequences of asthma disappeared for children with high
      educated mothers and children who did not experience poverty. Additionally, the
      socioeconomic disparities were not fully explained by healthcare resources,
      family process, and exposure to environment risks and the disparities were found
      for both mild and severe cases. These findings suggest that, to fully understand
      the developmental consequences of illness in children, it is important to place
      socioeconomic status at the center of investigation. 

PMID- 24937329
TI  - Perceived access to health services and provider information and adverse birth
      outcomes: findings from LaPRAMS, 2007-2008.
AB  - OBJECTIVES: Despite targeted public health efforts, racial disparities and poor
      birth outcomes are still apparent, particularly in the southern United States.
      Previous research through qualitative and modest quantitative research
      demonstrates a possible link between disparities in patient-provider
      conversations during prenatal visits, perceived access to prenatal care, and poor
      birth outcomes. METHODS: A secondary analysis was conducted using data from the
      2007-2008 Louisiana Pregnancy Risk Assessment Monitoring System to examine
      perceived access to healthcare services and information received and its impact
      on birth outcomes. Respondents consisted of 2460 white and black American women
      who recently experienced a live birth in the state of Louisiana. RESULTS: Racial
      disparities among Louisiana mothers were evident, with black mothers experiencing
      significant perceived lack of services or access to resources from a healthcare
      or insurance provider and poorer birth outcomes. White mothers reported
      experiencing less access based on the lack of vital prenatal care information
      from a healthcare provider. Self-perceived access was significantly associated
      with preterm birth for black women (odds ratio 2.94, 95% confidence interval 1-8;
      P < 0.05) and infant mortality for white women (odds ratio 340.5, confidence
      interval 36-999); P < 0.05). CONCLUSIONS: Findings support the need for a better
      understanding of discriminatory experiences and their impact on women's
      experiences during prenatal care and poor birth outcomes.

PMID- 24937328
TI  - Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to
      Crohn's disease in a Chinese family study.
AB  - BACKGROUND: Genetic variants make some contributions to inflammatory bowel
      disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). More
      than 100 susceptibility loci were identified in Western IBD studies, but
      susceptibility gene has not been found in Chinese IBD patients till now.
      Sequencing of individuals with an IBD family history is a powerful approach
      toward our understanding of the genetics and pathogenesis of IBD. The aim of this
      study, which focuses on a Han Chinese CD family, is to identify high-risk
      variants and potentially novel loci using whole exome sequencing technique.
      METHODS: Exome sequence data from 4 individuals belonging to a same family were
      analyzed using bioinformatics methods to narrow down the variants associated with
      CD. The potential risk genes were further analyzed by genotyping and Sanger
      sequencing in family members, additional 401 healthy controls (HC), 278 sporadic
      CD patients, 123 UC cases, a pair of monozygotic CD twins and another Chinese CD
      family. RESULTS: From the CD family in which the father and daughter were
      affected, we identified a novel single nucleotide variant (SNV) c.374T>C
      (p.I125T) in exon 4 of discs large homolog 1 (DLG1), a gene has been reported to
      play multiple roles in cell proliferation, T cell polarity and T cell receptor
      signaling. After genotyping among case and controls, a PLINK analysis showed the
      variant was of significance (P<0.05). 4 CD patients of the other Chinese family
      bore another non-synonymous variant c.833G>A (p.R278Q) in exon 9 of DLG1.
      CONCLUSIONS: We have discovered novel genetic variants in the coding regions of
      DLG1 gene, the results support that DLG1 is a novel potential susceptibility gene
      for CD in Chinese patients.

PMID- 24937330
TI  - Submaximal cardiopulmonary exercise testing for the evaluation of unexplained
      dyspnea.
AB  - OBJECTIVES: Gas exchange measurements obtained during submaximal exercise have
      been shown to provide prognostic and diagnostic information in patients with
      heart failure (HF) and to differentiate heart versus lung limitations in patients
      with unexplained dyspnea. The aim of our study was to assess the clinical utility
      of submaximal cardiopulmonary exercise testing using the Shape-HF equipment in
      identifying the cause of unexplained dyspnea. METHODS: A total of 65 patients
      underwent Shape-HF tests from September 2010 to June 2011 for unexplained dyspnea
      at our center. RESULTS: Of 65 patients, 39 were men and 26 were women. In this
      study, 23 patients had preexisting asthma or chronic obstructive pulmonary
      disease (COPD); 19 patients had a pacemaker (8), an implantable cardioverter
      defibrillator (2), or a cardiac resynchronization therapy defibrillator (CRT-D)
      (9). The study revealed that submaximal cardiopulmonary exercise testing provided
      supportive clinical data for deconditioning, pulmonary limitations (eg, COPD,
      interstitial lung disease, sleep apnea), pulmonary hypertension, and chronotropic
      incompetence in 21.5%, 23.1%, 13.8%, and 6.2% of patients, respectively.
      Pulmonary hypertension was confirmed in 55% of patients by echocardiography and
      lung problems were confirmed in 40% of patients by pulmonary function test and
      sleep study. Of nine patients with an implanted CRT-D, optimization of
      atrioventricular and interventricular programming was performed in seven (78%)
      using gas exchange monitoring while performing a steady state, low-level
      treadmill walk. CONCLUSIONS: Submaximal cardiopulmonary exercise testing has
      strongly suggested the diagnosis of COPD, interstitial lung disease, pulmonary
      hypertension, and deconditioning and has led to appropriate testing. Based on
      prior studies, we also used Shape-HF for its approved purpose of optimizing CRT-D
      programming in patients with HF, leading to clinical improvement.

PMID- 24937331
TI  - Epidemiology of the reported severity of cottonmouth (Agkistrodon piscivorus)
      snakebite.
AB  - OBJECTIVE: The goal of this study was to analyze trends in the annual rates of
      reported medical outcomes of cottonmouth (Agkistrodon piscivorus) snakebites in
      the United States, published in the annual reports of the American Association of
      Poison Control Centers in the course of 29 years. METHODS: This was a
      retrospective analysis of medical outcomes for cottonmouth snakebite victims who
      developed fatal, major, moderate, minor, or no effects. The annual rates for
      these medical outcomes were calculated by dividing the annual number of patients
      in each outcome category by the total annual number of people reported as being
      bitten by cottonmouths. Negative binomial regression was used to examine trends
      in annual rates. RESULTS: From 1985 through 2011, after controlling for the
      availability of CroFab, the annual incidence rate of cottonmouth snakebites
      causing no effect decreased significantly by 7.3%/year (incidence rate ratio
      [IRR] 0.927, 95% confidence interval [CI] 0.885-0.970), the incidence rate of
      minor outcomes did not change significantly (IRR 0.989, CI 0.974-1.006), the
      incidence rate of moderate outcomes increased significantly by 2.3%/year (IRR
      1.023, CI 1.004-1.042), and the incidence rate of major outcomes did not change
      significantly (IRR 0.987, CI 0.935-1.041). One fatality was reported in 2011.
      CONCLUSIONS: Annual rates of cottonmouth snakebites producing no effects
      decreased significantly, those producing minor outcomes did not change
      significantly, those producing moderate outcomes increased significantly, and
      those producing major outcomes did not change significantly, from 1985 through
      2011.

PMID- 24937332
TI  - Commentary on "Epidemiology of the reported severity of cottonmouth (Agkistrodon
      piscivorus) snakebite".

PMID- 24937333
TI  - Multiple cutaneous and hepatic hemangiomas in infants.
AB  - OBJECTIVES: The objectives of the study were to determine the rate of hepatic
      hemangiomas in infants with cutaneous infantile hemangiomas that were screened by
      abdominal ultrasound; identify morphological subtypes and number of cutaneous
      infantile hemangiomas that are likely to suggest the presence of hepatic
      hemangiomas; and identify clinical history, physical findings, or laboratory
      abnormalities that may predict hepatic involvement. METHODS: A retrospective
      study was conducted between 2000 and 2007 on 37 infants with cutaneous
      hemangiomas who underwent abdominal ultrasound for hepatic hemangiomas. Infants
      were classified into subgroups based upon the morphology of their cutaneous
      hemangioma(s). Data collected included clinical history, physical examination
      findings, sonographic findings, laboratory results, treatment(s) rendered, and
      clinical outcome. RESULTS: Eight of 37 infants (22%) had hepatic hemangiomas.
      Infants with miliary (30-100 pinpoint/small cutaneous hemangiomas), six or more
      small cutaneous hemangiomas, and one large with one or more small cutaneous
      hemangiomas were more likely to have concurrent hepatic hemangiomas. No other
      clinical findings were associated with hepatic involvement. CONCLUSIONS: Similar
      to other studies, our study found clinically asymptomatic hepatic hemangiomas in
      22% of infants with multiple cutaneous infantile hemangiomas. No clinical
      findings studied were predictive of hepatic involvement.

PMID- 24937334
TI  - Significance of high- and low-distal energy forearm fractures.
AB  - OBJECTIVE: To determine in men and women aged 50 years or older the proportion of
      distal forearm fractures related to high- or low-energy events and subsequent
      fracturing. METHODS: We reviewed records of patients presenting to emergency
      departments and urgent care facilities with distal forearm fractures occurring
      during a 7-year entry period and studied for an additional 3.5 years. RESULTS:
      High-energy events proportionally were 3.25 times more likely in men, whereas low
      energy distal forearm fractures proportionally were 7.98 times more likely in
      women. Although 25% received bone densitometry evaluations, only 3.59% were
      performed within the first year after a distal forearm fracture. Osteoporosis and
      osteopenia did not differ between high- and low-energy distal forearm fractures.
      In logistic regression, subsequent fractures were associated with prior fracture
      and age 80 years or older. The occurrence of individuals subsequently fracturing
      was similar in men and women. Compared with controls, the odds ratio of
      individuals subsequently fracturing was 1.74 (95% confidence interval 1.32-2.30)
      in women and 1.9 (95% confidence interval 1.07-3.43) in men. Approximately 60% of
      total subsequent fractures occurred within 3 years. Osteoporosis was
      significantly more in patients with distal forearm fractures than controls (P <
      0.001), but control patients had significantly more osteopenia (P < 0.001). No
      differences were noted in therapeutic intervention between those with prior
      distal forearm fractures and controls. CONCLUSIONS: Regardless of trauma
      occurrence, both men and women age 50 years and older with recent distal forearm
      fractures should be evaluated early for treatment by bone densitometry and
      clinical risk factors because the majority of recurrent fractures occur within 3
      years.

PMID- 24937335
TI  - Underrepresented minorities in academic medicine: is Florida better off?
AB  - OBJECTIVES: The state of Florida has experienced challenges recruiting and
      retaining underrepresented minority faculty in academic medicine, as well as
      maintaining a population-like balance of minority physicians practicing in the
      state. We sought to quantify the percentage of practicing minority physicians as
      compared to the general population of Florida and focus specifically on black,
      Hispanic, and Asian/Pacific Islander physicians in academic medicine. We
      hypothesized that because of the diversity of the state, the number of
      underrepresented minority academic physicians in Florida would be higher than the
      national average. METHODS: Data were derived and analyzed from a biennial survey
      initiated in 2007 that all physicians renewing licenses in Florida are required
      to complete. Fifty percent of the licensing cohort completes the survey annually.
      We focused on physician practice demographics and academic employment. RESULTS:
      Blacks make up 15.4% of the state population, 6.4% of practicing physicians, but
      only 3.9% of academic physicians. Hispanics are 22.8% of the state population,
      19.2% of practicing physicians, but only 12.5% of academic physicians. Asians are
      2.5% of the state population, 14.4% of practicing physicians, and 12.6% of
      academic physicians. Whites are 58% of the state population, 52% of practicing
      physicians, and 65% of academic physicians. CONCLUSIONS: There is disparity in
      clinical practice and academic medicine for blacks and Hispanics. Despite the
      diversity of the state, the disparity of blacks in academic medicine in Florida
      only marginally exceeds the national average. Asians and Hispanics make up the
      same percentage of academic physicians, but there are 10 times more Hispanics in
      the state. More research and programming are needed to further define and arrive
      at solutions to this problem.

PMID- 24937336
TI  - Commentary on "Underrepresented minorities in academic medicine: is Florida
      better off?".

PMID- 24937337
TI  - Advance care planning and proxy decision making for patients with advanced
      Parkinson disease.
AB  - OBJECTIVES: To examine advance care planning practices and proxy decision making
      by family healthcare proxies for patients with advanced Parkinson disease (PD).
      METHODS: Sixty-four spouses and adult children, self-designated as a/the
      healthcare proxy for advanced patients with PD, participated in a cross-sectional
      survey study. RESULTS: Sixty patients with PD (95%) had completed a living will,
      but only 38% had shared the document with a physician. Among three life-support
      treatments--cardiopulmonary resuscitation (CPR), ventilator, and feeding tube-
      47% of patients opted for CPR, 16% for ventilator, and 20% for feeding tube.
      Forty-two percent of proxies did not know patients' preferences for one or more
      of the three life-support treatments. Only 28% of proxies reported that patients
      wanted hospice. Patients who shared advance directives with a physician were
      significantly less likely to choose CPR and a feeding tube and they were more
      likely to choose hospice. In a hypothetical end-of-life (EOL) scenario, the
      majority of proxies chose comfort care as the EOL goal of care (53%) and pain and
      symptom management only as the course of treatment option (72%); these proxy
      choices for patients, however, were not associated with patients' preferences for
      life support. Patients' proxies preferred a form of shared decision making with
      other family members and physicians. CONCLUSIONS: Advance care planning is
      effective when patients, families, and healthcare professionals together consider
      future needs for EOL care decisions. Further efforts are needed by healthcare
      professionals to provide evidence-based education about care options and
      facilitate advanced discussion and shared decision making by the patient and
      families.

PMID- 24937338
TI  - Commentary on "Advance care planning and proxy decision making for patients with
      advanced Parkinson disease".

PMID- 24937339
TI  - Perceptions of companion dog benefits on well-being of US military veterans with
      HIV/AIDS.
AB  - OBJECTIVES: Patients with human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) frequently experience psychosocial complications
      in addition to physical illness. Conflicting data on the value of companion dog
      ownership in minimizing psychosocial distress suggest the need for more research
      in this field. This study helps to clarify and expand upon previous research on
      perceived well-being among patients with HIV/AIDS, specifically as it relates to
      how owning dogs influences the well-being of US military veterans living with
      HIV/AIDS. METHODS: Twenty-nine male veterans with a mean age of 52 years who
      reported having owned a dog since being diagnosed as having HIV/AIDS completed
      semistructured interviews regarding pet ownership and perceived well-being.
      Participants also completed a brief survey describing their pets and rating
      scales that assessed symptoms of depression (nine-question Patient Health
      Questionnaire-9) and the extent of attachment to their pets (Lexington Attachment
      to Pets Scale). Descriptive statistics were completed and interview responses
      were transcribed and examined qualitatively for key themes. RESULTS: The mean
      Patient Health Questionnaire-9 score of 8.9 (median score of 6) was consistent
      with mild depressive symptoms, and the mean Lexington Attachment to Pets Scale
      score was 83.2, indicative of high attachment to one's dog. Veterans reported
      walking their dogs a mean of 49 minutes/day. Qualitative analysis of the
      interviews showed that having HIV/AIDS interfered with well-being in three main
      ways (emotional burden, physical condition, and social isolation). Owning dogs
      enhanced perceived well-being in four ways (physical activity, companionship,
      responsibility, and stress reduction). CONCLUSIONS: Twenty-eight of the 29
      participants (97%) reported that owning dogs was a positive experience. Overall,
      this study suggests that veterans with HIV/AIDS who own companion dogs believe
      that it improves their well-being.

PMID- 24937340
TI  - Commentary on "Perceptions of companion dog benefits on well-being of US military
      veterans with HIV/AIDS".

PMID- 24937341
TI  - Hepatitis B in pregnancy.
AB  - In the United States each year, 24,000 infants are born to women who are infected
      with the hepatitis B virus (HBV) and an estimated 1000 newborns acquire the
      infection through vertical transmission from their mother. The approach to a
      pregnant patient with HBV infection includes assessing the need for therapy in
      the mother and evaluating possible interventions that may reduce mother-to-child
      transmission of HBV infection. Rates of mother-to-child transmission of HBV can
      be greatly reduced if the current guidelines for screening and immunization are
      universally followed. The use of oral antiviral therapy in highly viremic mothers
      to reduce mother-to-child transmission is controversial but should be considered
      on a case-by-case basis, realizing that the available antiviral medications to
      treat HBV are not approved by the Food and Drug Administration for use during
      pregnancy. We review the literature and present our suggested management approach
      to the pregnant patient with chronic HBV. 

PMID- 24937342
TI  - What happened to case reports?

PMID- 24937343
TI  - Editor's response.

PMID- 24937345
TI  - The epidemiology of Staphylococcus aureus transmission in the anesthesia work
      area.
AB  - BACKGROUND: Little is known regarding the epidemiology of intraoperative
      Staphylococcus aureus transmission. The primary aim of this study was to examine
      the mode of transmission, reservoir of origin, transmission locations, and
      antibiotic susceptibility for frequently encountered S aureus strains
      (phenotypes) in the anesthesia work area. Our secondary aims were to examine
      phenotypic associations with 30-day postoperative patient cultures, phenotypic
      growth rates, and risk factors for phenotypic isolation. METHODS: S aureus
      isolates previously identified as possible intraoperative bacterial transmission
      events by class of pathogen, temporal association, and analytical profile
      indexing were subjected to antibiotic disk diffusion sensitivity. The combination
      of these techniques was then used to confirm S aureus transmission events and to
      classify them as occurring within or between operative cases (mode). The origin
      of S aureus transmission events was determined via use of a previously validated
      experimental model and links to 30-day postoperative patient cultures confirmed
      via pulsed-field gel electrophoresis. Growth rates were assessed via time-to
      positivity analysis, and risk factors for isolation were characterized via
      logistic regression. RESULTS: One hundred seventy S aureus isolates previously
      implicated as possible intraoperative transmission events were further subdivided
      by analytical profile indexing phenotype. Two phenotypes, phenotype P (patients)
      and phenotype H (hands), accounted for 65% of isolates. Phenotype P and phenotype
      H contributed to at least 1 confirmed transmission event in 39% and 28% of cases,
      respectively. Patient skin surfaces (odds ratio [OR], 8.40; 95% confidence
      interval [CI], 2.30-30.73) and environmental (OR, 10.89; 95% CI, 1.29-92.13)
      samples were more likely than provider hands (referent) to have phenotype P
      positivity. Phenotype P was more likely than phenotype H to be resistant to
      methicillin (OR, 4.38; 95% CI, 1.59-12.06; P = 0.004) and to be linked to 30-day
      postoperative patient cultures (risk ratio, 36.63 [risk difference, 0.174; 95%
      CI, 0.019-0.328]; P < 0.001). Phenotype P exhibited a faster growth rate for
      methicillin resistant and for methicillin susceptible than phenotype H (phenotype
      P: median, 10.32H; interquartile range, 10.08-10.56; phenotype H: median, 10.56H;
      interquartile range, 10.32-10.8; P = 0.012). Risk factors for isolation of
      phenotype P included age (OR, 14.11; 95% CI, 3.12-63.5; P = 0.001) and patient
      exposure to the hospital ward (OR, 41.11; 95% CI, 5.30-318.78; P < 0.001).
      CONCLUSIONS: Two S aureus phenotypes are frequently transmitted in the anesthesia
      work area. A patient and environmentally derived phenotype is associated with
      increased risk of antibiotic resistance and links to 30-day postoperative patient
      cultures as compared with a provider hand-derived phenotype. Future work should
      be directed toward improved screening and decolonization of patients entering the
      perioperative arena and improved intraoperative environmental cleaning to
      attenuate postoperative health care-associated infections.

PMID- 24937347
TI  - The long-term impact of early cardiovascular therapy intensification for
      postoperative troponin elevation after major vascular surgery.
AB  - BACKGROUND: Acute cardiac events are a frequent cause of morbidity after vascular
      surgery. The impact of early evidence-based treatment for patients with an acute
      cardiac event after vascular surgery on long-term postoperative outcomes has not
      been extensively studied. We hypothesized that providing appropriate evidence
      based treatment to patients with elevated postoperative cardiac troponin levels
      may limit long-term mortality. METHODS: We conducted a study of 667 consecutive
      major vascular surgery patients with an elevated postoperative troponin I level.
      We then determined which of these patients received medical therapy as per the
      2007 American College of Cardiology/American Heart Association recommendations
      for the medical management of patients with chronic stable angina. All patients
      with troponin elevation were then matched with 2 control patients without
      postoperative troponin elevation. Matching was done using logistic regression and
      nearest-neighbor matching methods. The primary study end point was 12 months
      survival without a major cardiac event (i.e., death, myocardial infarction,
      coronary revascularization, or pulmonary edema requiring hospitalization).
      RESULTS: Therapy was intensified in 43 of 66 patients (65%) who suffered a
      troponin I elevation after surgery. Patients with a troponin I elevation not
      receiving intensified cardiovascular treatment had a hazard ratio (HR) of 1.77
      (95% confidence interval (CI), 1.13-2.42; P = 0.004) for the primary study
      outcome as compared with the control group. In contrast, patients with a troponin
      I elevation who received intensified cardiovascular treatment had an HR of 0.63
      (95% CI, 0.10-1.19; P = 0.45) for the primary outcome as compared with the
      control group. Patients with a troponin I elevation not receiving treatment
      intensification likely were at higher risk for a major cardiac event (HR, 2.80;
      95% CI, 1.05-24.2; P = 0.04) compared with patients who did receive treatment
      intensification. CONCLUSIONS: The main finding of this study was that in patients
      with elevated troponin I levels after noncardiac surgery, long-term adverse
      cardiac outcomes may likely be improved by following evidence-based
      recommendations for the medical management of acute coronary syndromes.

PMID- 24937346
TI  - The dynamics of Enterococcus transmission from bacterial reservoirs commonly
      encountered by anesthesia providers.
AB  - BACKGROUND: Enterococci, the second leading cause of health care-associated
      infections, have evolved from commensal and harmless organisms to multidrug
      resistant bacteria associated with a significant increase in patient morbidity
      and mortality. Prevention of ongoing spread of this organism within and between
      hospitals is important. In this study, we characterized Enterococcus transmission
      dynamics for bacterial reservoirs commonly encountered by anesthesia providers
      during the routine administration of general anesthesia. METHODS: Enterococcus
      isolates previously obtained from bacterial reservoirs frequently encountered by
      anesthesiologists (patient nasopharynx and axilla, anesthesia provider hands, and
      the adjustable pressure-limiting valve and agent dial of the anesthesia machine)
      at 3 major academic medical centers were identified as possible intraoperative
      bacterial transmission events by class of pathogen, temporal association, and
      phenotypic analysis (analytical profile indexing). They were then subjected to
      antibiotic disk diffusion sensitivity for transmission event confirmation.
      Isolates involved in confirmed transmission events were further analyzed to
      characterize the frequency, mode, origin, location of transmission events, and
      antibiotic susceptibility of transmitted pathogens. RESULTS: Three hundred eighty
      nine anesthesia reservoir isolates were previously identified by gross morphology
      and simple rapid tests as Enterococcus. The combination of further analytical
      profile indexing analysis and temporal association implicated 43% (166/389) of
      those isolates in possible intraoperative bacterial transmission events.
      Approximately, 30% (49/166) of possible transmission events were confirmed by
      additional antibiotic disk diffusion analysis. Two phenotypes, E5 and E7,
      explained 80% (39/49) of confirmed transmission events. For both phenotypes,
      provider hands were a common reservoir of origin proximal to the transmission
      event (96% [72/75] hand origin for E7 and 89% [50/56] hand origin for E5) and
      site of transmission (94% [16/17] hand transmission location for E7 and 86%
      [19/22] hand transmission location for E5). CONCLUSIONS: Anesthesia provider hand
      contamination is a common proximal source and transmission location for
      Enterococcus transmission events in the anesthesia work area. Future work should
      evaluate the impact of intraoperative hand hygiene improvement strategies on the
      dynamics of intraoperative Enterococcus transmission.

PMID- 24937349
TI  - Concreteness of positive word contributions to affective priming: an ERP study.
AB  - Recent behavioral data suggest that the concreteness of positive words modulates
      subsequent cognitive processing; however, the underlying physiological processes
      of this influence are not well understood. To explore this process, positive
      abstract words or positive-concrete words were used as primes when participants
      performed a lexical decision task during the measurement of event-related
      potentials (ERPs). The behavioral data revealed a significant affective priming
      effect (i.e., incongruent>congruent) only for abstract word pairs. The N400
      amplitude was larger for affectively incongruent pairs compared to affectively
      congruent pairs, independent of the prime concreteness. The amplitude of the late
      positive component (LPC) was modulated by prime concreteness. The processing of
      positive-abstract targets was facilitated by previous exposure to a congruent
      prime, as reflected by the reduced LPC, which has been thought to reflect
      attentional and memory processes. However, no differences in the LPC amplitude
      were found between congruent and incongruent-concrete pairs. These findings
      suggest that the influence of the concreteness of positive words mainly occurs
      during the decision-making processing and memory-related stages. 

PMID- 24937348
TI  - Hydrogen-rich saline improves survival and neurological outcome after cardiac
      arrest and cardiopulmonary resuscitation in rats.
AB  - BACKGROUND: Sudden cardiac arrest is a leading cause of death worldwide. Three
      fourths of cardiac arrest patients die before hospital discharge or experience
      significant neurological damage. Hydrogen-rich saline, a portable, easily
      administered, and safe means of delivering hydrogen gas, can exert organ
      protective effects through regulating oxidative stress, inflammation, and
      apoptosis. We designed this study to investigate whether hydrogen-rich saline
      treatment could improve survival and neurological outcome after cardiac arrest
      and cardiopulmonary resuscitation, and the mechanism responsible for this effect.
      METHODS: Sprague-Dawley rats were subjected to 8 minutes of cardiac arrest by
      asphyxia. Different doses of hydrogen-rich saline or normal saline were
      administered IV at 1 minute before cardiopulmonary resuscitation, followed by
      injections at 6 and 12 hours after restoration of spontaneous circulation,
      respectively. We assessed survival, neurological outcome, oxidative stress,
      inflammation biomarkers, and apoptosis. RESULTS: Hydrogen-rich saline treatment
      dose dependently improved survival and neurological function after cardiac
      arrest/resuscitation. Moreover, hydrogen-rich saline treatment dose dependently
      ameliorated brain injury after cardiac arrest/resuscitation, which was
      characterized by the increase of survival neurons in hippocampus CA1, reduction
      of brain edema in cortex and hippocampus, preservation of blood-brain barrier
      integrity, as well as the decrease of serum S100beta and neuron-specific enolase.
      Furthermore, we found that the beneficial effects of hydrogen-rich saline
      treatment were associated with decreased levels of oxidative products (8-iso
      prostaglandin F2alpha and malondialdehyde) and inflammatory cytokines (tumor
      necrosis factor-alpha, interleukin-1beta, and high-mobility group box protein 1),
      as well as the increased activity of antioxidant enzymes (superoxide dismutase
      and catalase) in serum and brain tissues. In addition, hydrogen-rich saline
      treatment reduced caspase-3 activity in cortex and hippocampus after cardiac
      arrest/resuscitation. CONCLUSIONS: Hydrogen-rich saline treatment improved
      survival and neurological outcome after cardiac arrest/resuscitation in rats,
      which was partially mediated by reducing oxidative stress, inflammation, and
      apoptosis.

PMID- 24937351
TI  - [Participatory Quality Development: Engaging Community Members in All Phases of
      Project Planning and Implementation].
AB  - Community participation, recognised as a central feature of successful health
      promotion and prevention, is often difficult to implement. In this research
      project internationally recognised methods of participatory health research were
      applied to demonstrate ways in which community members can be engaged.
      Participatory health research is characterised by a close collaboration between
      academic researchers, practitioners and community members in order to generate
      common knowledge. It is not a question of translating knowledge from research
      into practice, but rather a question of promoting a collective learning process
      on the part of all participants for the purpose of developing solutions which
      address the interests and needs of local people. The result of the project is a
      new approach for strengthening the quality of prevention and health promotion
      interventions: participatory quality development (PQD). 

PMID- 24937350
TI  - SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing
      the chronicity of hepatitis.
AB  - This study focused on investigating the pathogenesis seen in specific-pathogen
      free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN
      BJ-rb14) and comparing it to that seen following infection with a heterologous
      swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated
      with the homologous rabbit HEV became infected, exhibiting an intermittent
      viremia, obvious fluctuations of liver function biomarkers alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal
      virus shedding throughout the nine month study. In addition, liver histopathology
      showed both chronic inflammation and some degree of fibrosis. Both positive and
      negative-stranded HEV RNA and HEV antigen expression were detected in liver,
      brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of
      extrahepatic tissue (duodenum and kidney) was also observed. Three of the four
      rabbits inoculated with the heterologous genotype 4 swine HEV also became
      infected, showing similar levels of anti-HEV antibody to that generated following
      infection with the homologous virus isolate. The duration of both viremia and
      fecal shedding of virus was however shorter following infection with the
      heterologous virus and there was no significant elevation of liver function
      biomarkers. These results suggest that rabbit HEV infection may cause more severe
      hepatitis and prolong the course of the disease, with a possible chronic trend of
      hepatitis in SPF rabbits. 

PMID- 24937352
TI  - [Introduction of performance- and day-based lump-sum remuneration for stationary
      psychiatric and psychosomatic treatments in Germany--analysis of incentives of
      the PEPP system].
AB  - PURPOSE: This paper surveys the effects of day-based lump-sum remuneration as
      defined by the PEPP system on the patients' length of stay and compares its
      incentives to the mechanisms of the German DRG system and the former remunera
      tion system for stationary psychiatric and psychosomatic treatments. METHODS: The
      analysis identifies the economically optimal length of stay defined as the profit
      maximising duration of treatment by comparing marginal revenues and marginal
      costs. Since it is economically optimal to extend the treatment until the
      marginal costs exceed the marginal revenues, psychiatric and psychosomatic
      facilities are incentivised to minimise the time gap between average duration of
      treatment as expected duration of treatment and the economically optimal length
      of stay. RESULTS: Compared to the German DRG system, which provides a strong
      incentive to reduce length of stay, the incentives set by the PEPP system imply
      either a reduction or an extension of treatment duration depending on the
      underlying cost function. If a degressive cost function is assumed, which is
      typical for treatments of psychiatric and psychosomatic illnesses, the
      economically optimal duration of treatment will be at the last upper boundary of
      the interval of the marginal revenue function in which the average marginal
      revenues exceed the average marginal costs. It is also feasible that it is
      economically optimal to treat the patient for as long as possible. The hospital
      is incentivised to extend or reduce the time of treatment to this point in time.
      CONCLUSIONS: Psychiatric and psychosomatic hospitals are able to increase their
      profits by reducing or extending time of treatment. Therefore these facilities
      have to justify the extent of treatment to the health insurance companies. Since
      the incentives of the PEPP system and the DRG system diverge, the results of
      research on supply induced demand in the DRG system cannot be transferred to the
      discussion about the effects of the introduction of the PEPP system. As long as
      the average duration of treatment as expected duration of treatment deviates from
      the economically optimal length of stay, policy makers should consider the
      options of adaptations, i. e., increase of time intervals or calculating cost
      weights based on variable costs combined with separate remuneration of fixed
      costs. The TEPP system and PEPPplus are already being discussed as adaptions or
      additions.

PMID- 24937353
TI  - Insights on the origin of the unusually large specific rotation of (1S,4S)
      norbornenone.
AB  - Measurements and calculations of specific rotation are indispensable for the
      characterization of chiral molecules and are now performed routinely. However,
      the factors that determine the magnitude of this property are still not well
      understood. The anomalously large specific rotation of (1S,4S)-norbornenone, an
      outstanding puzzle for over three decades, offers the chance to examine these
      factors in detail. The present work provides an explanation for the unusual
      behavior of this molecule in terms of interactions between chemical groups and
      electronic excited-state transition properties by means of ab initio density
      functional theory and coupled cluster theory calculations. We show that one can
      focus on the first excited state and examine the relative orientation of its
      electric and magnetic transition dipole moments. The contribution of the two
      transition moments of this electronic state to the specific rotation in a sum
      over-states formalism reveals a constructive interaction that is possible only
      when the two chromophores in norbornenone (C?O and C?C) are in-plane and pointing
      away from each other. This is due to a small but non-negligible charge transfer
      between the chromophores and is consistent with recent results from Autschbach's
      group [Moore et al., J. Chem. Theory Comput. 2012, 8, 4336-4346]. The analysis in
      this work improves our understanding of this fundamental property of chiral
      molecules and may help in the design of other molecules with large specific
      rotation. 

PMID- 24937354
TI  - Bottom-up synthesis of anatase nanoparticles with graphene domains.
AB  - Using alizarin and titanium isopropoxide, we have succeeded in preparing a hybrid
      form of nanostructured graphene-TiO2 following a bottom-up synthetic approach.
      This novel graphene-based composite offers a practical alternative to
      synthesizing photocatalytically active materials with maximized graphene-TiO2
      interface. The molecular precursor alizarin was chosen because it efficiently
      binds to TiO2 through the hydroxyl groups and already possesses the graphene
      building block through its anthracene basis. XPS and Raman spectroscopy proved
      that the calcined material contained majority sp(2)-hybridized carbon that formed
      graphene-like clusters. XRD data showed the integrated structures maintained
      their anatase crystallography, therefore preserving the material's properties
      without going through phase transitions to rutile. The enhanced graphene and TiO2
      interface was confirmed using DFT computational techniques. The photocatalytic
      activity of the graphene-TiO2 materials was demonstrated through degradation of
      methylene blue. 

PMID- 24937355
TI  - Early rehabilitative treatment for pediatric acute disseminated
      encephalomyelitis: case report.
AB  - Although the diagnosis of and therapy for acute disseminated encephalomyelitis
      (ADEM) have been extensively investigated, the role of rehabilitation in
      modifying its functional outcome has received little attention in the literature
      so far. We report a case of pediatric ADEM who showed complete functional
      recovery following early rehabilitative treatment, started in the Intensive Care
      Unit. 

PMID- 24937356
TI  - Abundance and composition of indigenous bacterial communities in a multi-step
      biofiltration-based drinking water treatment plant.
AB  - Indigenous bacterial communities are essential for biofiltration processes in
      drinking water treatment systems. In this study, we examined the microbial
      community composition and abundance of three different biofilter types (rapid
      sand, granular activated carbon, and slow sand filters) and their respective
      effluents in a full-scale, multi-step treatment plant (Zurich, CH). Detailed
      analysis of organic carbon degradation underpinned biodegradation as the primary
      function of the biofilter biomass. The biomass was present in concentrations
      ranging between 2-5 * 10(15) cells/m(3) in all filters but was phylogenetically,
      enzymatically and metabolically diverse. Based on 16S rRNA gene-based 454
      pyrosequencing analysis for microbial community composition, similar microbial
      taxa (predominantly Proteobacteria, Planctomycetes, Acidobacteria, Bacteriodetes,
      Nitrospira and Chloroflexi) were present in all biofilters and in their
      respective effluents, but the ratio of microbial taxa was different in each
      filter type. This change was also reflected in the cluster analysis, which
      revealed a change of 50-60% in microbial community composition between the
      different filter types. This study documents the direct influence of the filter
      biomass on the microbial community composition of the final drinking water,
      particularly when the water is distributed without post-disinfection. The results
      provide new insights on the complexity of indigenous bacteria colonizing drinking
      water systems, especially in different biofilters of a multi-step treatment
      plant.

PMID- 24937357
TI  - An overview on the reactors to study drinking water biofilms.
AB  - The development of biofilms in drinking water distribution systems (DWDS) can
      cause pipe degradation, changes in the water organoleptic properties but the main
      problem is related to the public health. Biofilms are the main responsible for
      the microbial presence in drinking water (DW) and can be reservoirs for
      pathogens. Therefore, the understanding of the mechanisms underlying biofilm
      formation and behavior is of utmost importance in order to create effective
      control strategies. As the study of biofilms in real DWDS is difficult, several
      devices have been developed. These devices allow biofilm formation under
      controlled conditions of physical (flow velocity, shear stress, temperature, type
      of pipe material, etc), chemical (type and amount of nutrients, type of
      disinfectant and residuals, organic and inorganic particles, ions, etc) and
      biological (composition of microbial community - type of microorganism and
      characteristics) parameters, ensuring that the operational conditions are similar
      as possible to the DWDS conditions in order to achieve results that can be
      applied to the real scenarios. The devices used in DW biofilm studies can be
      divided essentially in two groups, those usually applied in situ and the bench
      top laboratorial reactors. The selection of a device should be obviously in
      accordance with the aim of the study and its advantages and limitations should be
      evaluated to obtain reproducible results that can be transposed into the reality
      of the DWDS. The aim of this review is to provide an overview on the main
      reactors used in DW biofilm studies, describing their characteristics and
      applications, taking into account their main advantages and limitations. 

PMID- 24937358
TI  - Sequestration of phosphorus from wastewater by cement-based or alternative
      cementitious materials.
AB  - Cement-based and alternative cementitious materials were tested in the laboratory
      for their capability of removing phosphate from wastewater. The results
      demonstrated that both Langmuir and Freundlich adsorption isotherms were suitable
      for describing the adsorption characteristics of these materials. Among the four
      types of filter media tested, the cement-based mortar A has the highest value of
      maximum adsorption (30.96 mg g(-1)). The P-bonding energy (KL) and adsorption
      capacity (K) exhibited a positive correlation with the total content of Al2O3 and
      Fe2O3 in each mortar. The maximum amount of P adsorbed (Qm) and adsorption
      intensity (1/n) exhibited a positive correlation with the CaO content in each
      mortar. For three of them, the P-removal rates were in excess of 94 percent for
      phosphorus concentrations ranging from 20 to 1000 mg L(-1). The underlying
      mechanisms were examined using field emission scanning microscopy (FESEM),
      coupled with energy-dispersive X-ray spectroscopy (EDX) and X-ray powder
      diffraction (XRD). The results reveal that the removal of phosphate predominantly
      followed a precipitation mechanism in addition to weak physical interactions
      between the surface of adsorbent filter media and the metallic salts of
      phosphate. The use of cement-based or alternative cementitious materials in the
      form of ground powder shows great promise for developing a cost-effective and
      environmentally sustainable technology for P-sequestration and for wastewater
      treatment.

PMID- 24937359
TI  - Fate of antibiotic resistance genes in sewage treatment plant revealed by
      metagenomic approach.
AB  - Antibiotic resistance has become a serious threat to human health. Sewage
      treatment plant (STP) is one of the major sources of antibiotic resistance genes
      (ARGs) in natural environment. High-throughput sequencing-based metagenomic
      approach was applied to investigate the broad-spectrum profiles and fate of ARGs
      in a full scale STP. Totally, 271 ARGs subtypes belonging to 18 ARGs types were
      identified by the broad scanning of metagenomic analysis. Influent had the
      highest ARGs abundance, followed by effluent, anaerobic digestion sludge and
      activated sludge. 78 ARGs subtypes persisted through the biological wastewater
      and sludge treatment process. The high removal efficiency of 99.82% for total
      ARGs in wastewater suggested that sewage treatment process is effective in
      reducing ARGs. But the removal efficiency of ARGs in sludge treatment was not as
      good as that in sewage treatment. Furthermore, the composition of microbial
      communities was examined and the correlation between microbial community and ARGs
      was investigated using redundancy analysis. Significant correlation between 6
      genera and the distribution of ARGs were found and 5 of the 6 genera included
      potential pathogens. This is the first study on the fate of ARGs in STP using
      metagenomic analysis with high-throughput sequencing and hopefully would enhance
      our knowledge on fate of ARGs in STP. 

PMID- 24937360
TI  - Two-nanometer voids in single-layer hexagonal boron nitride: formation via the
      "can-opener" effect and annihilation by self-healing.
AB  - The exposure of hexagonal boron nitride single layers to low energy ions leads to
      the formation of vacancy defects that are mobile at elevated temperatures. For
      the case of h-BN on rhodium, a superhoneycomb surface with 3 nm lattice constant
      (nanomesh), a concerted self-assembly of these defects is observed, where the
      "can-opener" effect leads to the cut-out of 2 nm "lids" and stable voids in the h
      BN layer. These clean-cut voids repel each other, which enables the formation of
      arrays with a nearest neighbor distance down to about 8 nm. The density of voids
      depends on the Ar ion dose, and can reach 10(12) cm(-2). If the structures are
      annealed above 1000 K, the voids disappear and pristine h-BN nanomesh with larger
      holes is recovered. The results are obtained by scanning tunneling microscopy and
      density functional theory calculations. 

PMID- 24937361
TI  - Nutrition considerations in special environments for aquatic sports.
AB  - Elite athletes who compete in aquatic sports face the constant challenge of
      arduous training and competition schedules in difficult and changing
      environmental conditions. The huge range of water temperatures to which swimmers
      and other aquatic athletes are often exposed (16-31  degrees C for open-water
      swimming), coupled with altered aquatic thermoregulatory responses as compared
      with terrestrial athletes, can challenge the health, safety, and performance of
      these athletes. Other environmental concerns include air and water pollution,
      altitude, and jetlag and travel fatigue. However, these challenging environments
      provide the potential for several nutritional interventions that can mitigate the
      negative effects and enhance adaptation and performance. These interventions
      include providing adequate hydration and carbohydrate and iron intake while at
      altitude; optimizing body composition and fluid and carbohydrate intake when
      training or competing in varying water temperatures; and maximizing fluid and
      food hygiene when traveling. There is also emerging information on nutritional
      interventions to manage jetlag and travel fatigue, such as the timing of food
      intake and the strategic use of caffeine or melatonin. Aquatic athletes often
      undertake their major global competitions where accommodations feature cafeteria
      style buffet eating. These environments can often lead to inappropriate choices
      in the type and quantity of food intake, which is of particular concern to divers
      and synchronized swimmers who compete in physique-specific sports, as well as
      swimmers who have a vastly reduced energy expenditure during their taper. Taken
      together, planned nutrition and hydration interventions can have a favorable
      impact on aquatic athletes facing varying environmental challenges. 

PMID- 24937364
TI  - Embedding NiCo2O4 nanoparticles into a 3DHPC assisted by CO2-expanded ethanol: a
      potential lithium-ion battery anode with high performance.
AB  - A high-performance anode material, NiCo2O4/3DHPC composite, for lithium-ion
      batteries was developed through direct nanoparticles nucleation on a three
      dimensional hierarchical porous carbon (3DHPC) matrix and cation substitution of
      spinel Co3O4 nanoparticles. It was synthesized via a supercritical carbon dioxide
      (scCO2) expanded ethanol solution-assisted deposition method combined with a
      subsequent heat-treatment process. The NiCo2O4 nanoparticles were uniformly
      embedded into the porous carbon matrix and efficiently avoided free-growth in
      solution or aggregation in the pores even at a high content of 55.0 wt %. In
      particular, the 3DHPC was directly used without pretreatment or surfactant
      assistance. As an anode material for lithium-ion batteries, the NiCo2O4/3DHPC
      composite showed high reversible capacity and improved rate capability that
      outperformed those composites formed with single metal oxides (NiO/3DHPC,
      Co3O4/3DHPC), their physical mixture, and the composite prepared in pure ethanol
      (NiCo2O4/3DHPC-E). The superior performance is mainly contributed to the unique
      advantages of the scCO2-expanded ethanol medium, and the combination of high
      utilization efficiency and improved electrical conductivity of NiCo2O4 as well as
      the electronic and ionic transport advantages of 3DHPC. 

PMID- 24937365
TI  - Exploring macrocycles in functional supramolecular gels: from stimuli
      responsiveness to systems chemistry.
AB  - CONSPECTUS: Supramolecular gels are ideal candidates for soft, stimuli-responsive
      materials, because they combine the elastic behavior of solids with the
      microviscous properties of fluids. The dynamic networks of fibers in
      supramolecular gels are reminiscent of the cytoskeleton of a cell and provide
      scaffolds to implement function. When gels are made responsive to stimuli, these
      mechanical properties can be controlled. Gel-sol transitions also open
      opportunities to immobilize molecules inside the gel's cavities and to release
      them on demand. To establish selective responsiveness, suitable recognition sites
      are required influencing the properties of the fiber network depending on the
      presence of the stimulus. Supramolecular gels are expected to be stimuli
      responsive per se, for example, to temperature, mechanical stress, or an
      environment that is competitive with the noncovalent interactions connecting the
      low-molecular weight gelators. Nevertheless, the opportunities for controlling
      the mechanical properties are rather limited, if one merely relies on interfering
      with these interactions. It would be much more promising to equip the gel with
      additional receptor sites that offer selectivity for a broader variety of
      chemical stimuli. Macrocycles often exhibit a distinct host-guest chemistry and
      thus are excellent candidates for this purpose. A broad variety of macrocycles
      differing with respect to structure, topology, solubility, or biocompatibility
      have been incorporated in gels and endow gels with responsiveness and function.
      Macrocycles can have different roles: They offer rather rigid scaffolds for the
      construction of structurally well-defined gelator molecules. Furthermore, their
      host-guest interactions can be integral to gel formation, if these interactions
      are required to build the gel fibers. Finally, macrocycles can also be functional
      groups with which gelators are equipped that would also form gels in the absence
      of the macrocycle. Here, the macrocycle can be used as a binding site to allow
      additional stimuli control. To combine different stimuli for triggering gel-sol
      transitions certainly expands the options for establishing stimuli
      responsiveness. If, for example, an agent trapped inside the gel is only
      liberated when two different stimuli are present simultaneously, its release can
      be controlled with much higher precision and selectivity compared with a gel that
      responds to one stimulus only. In this Account, the recent progress in the
      construction of functional macrocycle-containing supramolecular gels is
      summarized. First, recent strategies to engineer responsiveness into macrocycle
      containing gels are discussed. Next, different functions are presented including
      applications as responsive reaction media, for controlled drug-delivery or tissue
      engineering, and as self-healing materials. Finally, we highlight the recent
      progress in designing macrocycle-containing supramolecular gel materials
      exhibiting complex behavior. This field is part of systems chemistry and still in
      its infancy but appears to be one of the most promising routes to smart
      responsive materials.

PMID- 24937366
TI  - Balticidins A-D, antifungal hassallidin-like lipopeptides from the Baltic Sea
      cyanobacterium Anabaena cylindrica Bio33.
AB  - Balticidins A-D (1-4), four new antifungal lipopeptides, were isolated from the
      laboratory-cultivated cyanobacterium Anabaena cylindrica strain Bio33 isolated
      from a water sample collected from the Baltic Sea, Rugen Island, Germany.
      Fractionation of the 50% aqueous MeOH extract was performed by bioassay-guided
      silica gel column chromatography followed by SPE and repeated reversed-phase
      HPLC. The main fraction containing the compounds exhibited a strong and specific
      antifungal activity with inhibition zones in an agar-diffusion assay from 21 to
      32 mm against Candida albicans, Candida krusei, Candida maltosa, Aspergillus
      fumigatus, Microsporum gypseum, Mucor sp., and Microsporum canis. The structures
      were elucidated by multidimensional (1)H and (13)C NMR spectroscopy, HRESIMS,
      amino acid analysis, and sugar analysis. Spectroscopic data analysis afforded an
      unambiguous sequence of R.CHO(S1).CHOH.CONH-Thr(1)-Thr(2)-Thr(3)-HOTyr(4)-Dhb(5)
      D-Gln(6)-Gly(7)-NMeThr(8)(S2)-L-Gln COOH(9), in which Dhb is dehydroaminobutyric
      acid, S1 is d(-)-arabinose-(3-1)-D-(+)-galacturonic acid, S2 is D-(+)-mannose,
      and R is the aliphatic residue -C13H26Cl or -C13H27. Besides NMeThr, D-allo-Thr,
      D-Thr, and L-Thr were identified, but the position of the enantiomers in the
      sequence is not clear. The four balticidins differ in their cyclic (2, 4)/linear
      (1, 3) core and the presence (1, 2)/absence (3, 4) of chlorine in the aliphatic
      unit.

PMID- 24937368
TI  - Ionizing radiation-induced oxidative stress, epigenetic changes and genomic
      instability: the pivotal role of mitochondria.
AB  - PURPOSE: To review the data concerning the role of endogenously generated
      reactive oxygen species (ROS) in the non-targeted ionizing radiation (IR) effects
      and in determination of the cell population's fate, both early after exposure and
      after many generations. CONCLUSIONS: The short-term as well as chronic oxidative
      stress responses mainly are produced due to ROS generation by the electron
      transport chain (ETC) of the mitochondria and by the cytoplasmic NADPH oxidases.
      Whether the induction of the oxidative stress and its consequences occur or are
      hampered in a single cell largely depends on the interaction between the nucleus
      and the cellular population of several hundred or thousands of mitochondria that
      are genetically heterogeneous. High intra-mitochondrial ROS level is damaging the
      mitochondrial (mt) DNA and its mutations affect the epigenetic control mechanisms
      of the nuclear (n) DNA, by decreasing the activity of methyltransferases and
      thus, causing global DNA hypomethylation. These changes are transmitted to the
      progeny of the irradiated cells. The chronic oxidative stress is the main cause
      of the late post-radiation effects, including cancer, and this makes it an
      important adverse effect of exposure to IR and a target for radiological
      protection.

PMID- 24937367
TI  - Increased risk of long-term sickness absence, lower rate of return to work, and
      higher risk of unemployment and disability pensioning for thyroid patients: a
      Danish register-based cohort study.
AB  - CONTEXT: Little is known about how thyroid diseases affect work ability.
      OBJECTIVE: The objective of this study was to evaluate the risk of work
      disability for patients with thyroid disease compared with the general
      population. DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal register study,
      outpatients (n = 862) with nontoxic goiter, hyperthyroidism, Graves' orbitopathy
      (GO), autoimmune hypothyroidism, or other thyroid diseases and their matched
      controls (n = 7043) were observed in the years 1994-2011 in Danish national
      registers of social benefits, health, and work characteristics. Cox regression
      analyses estimated adjusted hazard ratios (HRs) for the first year after
      diagnosis and subsequent years. MAIN OUTCOME MEASURES: Transitions between work,
      long-term sickness absence, unemployment, and disability pension were measured.
      RESULTS: Patients differed significantly from the general population with regard
      to sickness absence, disability pension, return from sickness absence, and
      unemployment. In the first year after diagnosis, higher risks of sickness absence
      was seen for GO (HR 6.94) and other hyperthyroid patients (HR 2.08), who also had
      lower probability of returning from sickness absence (HR 0.62) and higher risk of
      disability pension (HR 4.15). Patients with autoimmune hypothyroidism showed a
      lower probability of returning from sickness absence (HR 0.62). In subsequent
      years, GO patients had significantly higher risk of sickness absence (HR 2.08),
      lower probability of return from sickness absence (HR 0.51), and unemployment (HR
      0.52) and a higher risk of disability pension (HR 4.40). Hyperthyroid patients
      also had difficulties returning from sickness absence (HR 0.71). CONCLUSIONS:
      Thyroid patients' risk of work disability is most pronounced in the first year
      after diagnosis and attenuates in subsequent years. GO patients have the highest
      risk of work disability.

PMID- 24937369
TI  - Effects of pre-irradiation and SDF-1 suppression on the progression of murine
      astrocytoma cells grown in different stromal beds.
AB  - PURPOSE: To examine whether brain tumors grown in pre-irradiated (PreIR) thigh
      have a similar tumor bed effect (TBE) as in PreIR brain tissue. MATERIAL AND
      METHODS: Tumor growth delay and immunohistochemical (IHC) staining for CD31, an
      endothelial surface marker, and PIMO, a hypoxia marker, were used to study the
      TBE of a murine astrocytoma, ALTS1C1, or a stromal-derived factor-1 (SDF-1) gene
      silenced astrocytoma, ALTS1C1-SDFkd, growing in different PreIR stroma beds.
      RESULTS: ALTS1C1 tumors growing in both PreIR brain and PreIR thigh had reduced
      microvascular density (MVD) and more chronic hypoxia, but tumor growth delay was
      only seen in PreIR brain tissue. In contrast, ALTS1C1-SDFkd tumors showed tumor
      growth delay in PreIR thigh, with little effect in PreIR brain tissue.
      CONCLUSIONS: This study cautions that both the tumor and the nature of the PreIR
      stromal bed are important when using pre-irradiation as a model of recurrent
      brain tumors after radiation therapy.

PMID- 24937370
TI  - PARP inhibitor attenuated colony formation can be restored by MAP kinase
      inhibitors in different irradiated cancer cell lines.
AB  - Abstract Purpose: Sensitizing cancer cells to irradiation is a major challenge in
      clinical oncology. We aimed to define the signal transduction pathways involved
      in poly(ADP-ribose) polymerase (PARP) inhibitor-induced radiosensitization in
      various mammalian cancer lines. MATERIALS AND METHODS: Clonogenic survival assays
      and Western blot examinations were performed following telecobalt irradiation of
      cancer cells in the presence or absence of various combinations of PARP- and
      selective mitogen-activated protein kinase (MAPK) inhibitors. RESULTS: HO3089
      resulted in significant cytotoxicity when combined with irradiation. In human
      U251 glioblastoma and A549 lung cancer cell lines, Erk1/2 and JNK/SAPK were found
      to mediate this effect of HO3089 since inhibitors of these kinases ameliorated
      it. In murine 4T1 breast cancer cell line, p38 MAPK rather than Erk1/2 or
      JNK/SAPK was identified as the main mediator of HO3089's radiosensitizing effect.
      Besides the aforementioned changes in kinase signaling, we detected increased
      p53, unchanged Bax and decreased Bcl-2 expression in the A549 cell line.
      CONCLUSIONS: HO3089 sensitizes cancer cells to photon irradiation via
      proapoptotic processes where p53 plays a crucial role. Activation of MAPK
      pathways is regarded the consequence of irradiation-induced DNA damage, thus
      their inhibition can counteract the radiosenzitizing effect of the PARP
      inhibitor.

PMID- 24937371
TI  - Fish oil omega-3 fatty acids reduce the severity of radiation-induced oxidative
      stress in the rat brain.
AB  - PURPOSE: To evaluate the modulator role of fish oil (FO) on some biochemical
      changes in the brain of gamma-irradiated rats (RAD). MATERIAL AND METHODS: Male
      albino rats Sprague Dawley were divided into four groups (n = 10). (i) CONTROL:
      received vehicle via gavages during 28 days; (ii) FO: received fish oil (400
      mg/kg/day) via gavages during 28 days; (iii) RAD: received vehicle for 7 days
      before whole body gamma-irradiation with 8 Gy given in four fractions each 7 days
      apart and continued during the irradiation period; and (iv) FO+ RAD: received FO
      for 7 days before exposure to the first dose of irradiation and FO treatment was
      continued during the irradiation period. Animals were sacrificed 24 hours post
      the last irradiation dose. RESULTS: A significant increase of malondialdehyde
      (MDA) and protein carbonyl (CO) content associated with a significant decrease of
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)
      activities and glutathione (GSH) content were recorded in the brain of irradiated
      rats. Oxidative stress was accompanied by a significant decrease of
      eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels. Aspartic (Asp) and
      glutamic (Glu) acid levels were increased. Serotonin level showed a decrease
      associated with enhanced monoamine oxidase (MAO) activity and increased 5
      hydroxyindolacetic acid (5-HIAA) level. FO treatment reduced the severity of
      radiation-induced oxidative stress, alteration of Asp and Glu levels and
      serotonin metabolism concomitant with increased EPA and DHA levels. CONCLUSION:
      FO attenuates the severity of radiation-induced biochemical disorders in the
      brain by counteracting the radiation-induced decrease of EPA and DHA. Further
      studies are needed concerning the long-term implications of our findings.

PMID- 24937372
TI  - (238)Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in
      female and male Swiss-Webster mice.
AB  - PURPOSE: To characterize the dose-dependent and sex-related efficacy of the
      hydroxypyridinonate decorporation agent 3,4,3-LI(1,2-HOPO) at enhancing plutonium
      elimination when post-exposure treatment is delayed. MATERIALS AND METHODS: Six
      parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 MUmol/kg were evaluated
      for decorporating plutonium in female and male Swiss-Webster mice administered a
      soluble citrate complex of (238)Pu and treated 24 hours later. Necropsies were
      scheduled at four time-points (2, 4, 8, and 15 days post-contamination) for the
      female groups and at three time-points (2, 4, and 8 days post-contamination) for
      the male groups. RESULTS: Elimination enhancement was dose-dependent in the 1-100
      MUmol/kg dose range at all necropsy time-points, with some significant reductions
      in full body and tissue content for both female and male animals. The highest
      dose level resulted in slight toxicity, with a short recovery period, which
      delayed excretion of the radionuclide. CONCLUSIONS: While differences were noted
      between the female and male cohorts in efficacy range and recovery times, all
      groups displayed sustained dose-dependent (238)Pu elimination enhancement after
      delayed parenteral treatment with 3,4,3-LI(1,2-HOPO), the actinide decorporation
      agent under development.

PMID- 24937373
TI  - The effects of chronic gamma irradiation on oxidative stress response and the
      expression of anthocyanin biosynthesis-related genes in wheat (Triticum
      aestivum).
AB  - PURPOSE: To investigate the mechanisms of adaptation and tolerance to ionizing
      radiation using chronic radiation in wheat. MATERIALS AND METHODS: We exposed
      wheat plants to chronic gamma irradiation (50 Gy) for 2, 4, and 6 weeks and
      measured various biological parameters. RESULTS: Plant height was reduced by
      exposure to gamma irradiation; this effect increased with increasing exposure
      time. Photosynthetic pigment levels decreased with increasing exposure time,
      while anthocyanin levels significantly increased after exposure to gamma rays.
      The activities of antioxidant enzymes (superoxide dismutase [SOD], ascorbate
      peroxidase [APX], catalase [CAT], and peroxidase [POD]) and malondialdehyde (MDA)
      levels increased with increasing duration of exposure to gamma irradiation.
      Electron spin resonance (ESR) signals were strongly detected in wheat that was
      gamma-irradiated for two weeks and then gradually decreased with increasing
      exposure time. The expression of anthocyanin biosynthesis genes (flavanone 3
      hydroxylase [F3H], dihydroflavonol reductase [DFR], anthocyanin reductase [ANS],
      and UDPG-flavonoid glucosyl transferase [UFGT]) and sugar contents increased
      after exposure to gamma rays. CONCLUSIONS: This suggests that exposure to
      ionizing radiation according to increase of exposure time has led to efficient
      induction of anthocyanin and antioxidant enzyme activities. This study indicates
      that reactive oxygen species (ROS) is eliminated by biosynthesis of anthocyanin
      and antioxidant enzymes. This study helps elucidate the biological effects of
      various durations of low-dose exposure to chronic gamma radiation in wheat
      plants.

PMID- 24937377
TI  - Safety evaluation of naringenin upon experimental exposure on rat
      gastrointestinal epithelium for novel optimal drug delivery.
AB  - OBJECTIVE: To assess the effect of naringenin on the intestinal biochemical
      composition, function and histology for gastrointestinal toxicity since it has
      not yet been adequately exploited for safety through standard assays. METHODS:
      Here, we describe naringenin (1 mM, 10 mM and 100 mM, respectively) or sodium
      deoxycholate (10 mM) effects on isolated brush border membrane from intestinal
      segments with single pass intestinal perfusion using lactate dehydrogenase,
      alkaline phosphatase and protein assays. MTT assay was used for cytotoxicity
      studies. Everted gut sac studies were used for evaluating the transport of
      nutrients across the intestinal segments. Lucifer yellow was used for
      paracellular permeability, followed by histological changes and surface
      characteristic studies of intestinal sacs. RESULTS: The results indicated no
      significant alterations with naringenin, although significant (p < 0.01) changes
      were noticed with sodium deoxycholate in the activity of the rat intestinal brush
      border associated enzymes such as LDH, followed by intact cell viability with
      marked decrease in the villi height of the intestinal segments. CONCLUSIONS:
      These observations indicate that naringenin was harmless upon exposure to rat
      gastrointestinal epithelium, clearly demonstrating the potential use of naturally
      occurring bioflavonoid as safe and novel pharmaceutical adjuvant in oral dosage
      forms as P-gp inhibitor.

PMID- 24937374
TI  - Cellular response of the rat brain to single doses of (137)Cs gamma rays does not
      predict its response to prolonged 'biologically equivalent' fractionated doses.
AB  - PURPOSE: To determine if the brain's response to single doses predicts its
      response to 'biologically equivalent' fractionated doses. METHODS: Young adult
      male Fischer 344 rats were whole-brain irradiated with either single 11, 14, or
      16.5 Gy doses of (137)Cs gamma rays or their 'biologically equivalent' 20, 30, or
      40 Gy fractionated doses (fWBI) delivered in 5 Gy fractions, twice/week for 2, 3,
      or 4 weeks, respectively. At 2 months post-irradiation, cellular markers of
      inflammation (total, activated, and newborn microglia) and neurogenesis (newborn
      neurons) were measured in 40 MUm sections of the dentate gyrus (DG). RESULTS:
      Although the total number of microglia in the DG/hilus was not significantly
      different (p > 0.7) in unirradiated, single dose, and fWBI rats, single doses
      produced a significant (p < 0.003) increase in the percent-activated microglia;
      fWBI did not (p > 0.1). Additionally, single doses produced a significant (p <
      0.002) dose-dependent increase in surviving newborn microglia; fWBI did not (p <
      0.8). Although total proliferation in the DG was reduced equally by single and
      fWBI doses, single doses produced a significant dose-dependent (p < 0.02)
      decrease in surviving newborn neurons; fWBI did not (p > 0.6). CONCLUSIONS: These
      data demonstrate that the rat brain's cellular response to single doses often
      does not predict its cellular response to 'biologically equivalent' fWBI doses.

PMID- 24937378
TI  - Nanostructured lipid carriers of pioglitazone for transdermal application: from
      experimental design to bioactivity detail.
AB  - Pioglitazone (PZ) an anti-hyperglycemic agent is used in the treatment of type 2
      diabetes. The aim of this study was to design PZ-loaded nanostructured lipid
      carriers (NLC) to investigate the bioavailability improvement by transdermal
      delivery. PZ NLCs were prepared using high-pressure homogenization followed by
      ultrasonication. The NLCs were evaluated for particle size analysis, drug
      loading, ex vivo skin transport studies and in vivo bioactivity study. The
      prepared NLCs had a mean size of 166.05 nm and drug loading of 10.41% with flux
      value of 47.36 ug/cm(2)/h. The entrapment of PZ is >70% in the NLCs with
      enhancement ratio of 3.2 times. The in vivo pharmacokinetic study showed 2.17
      times enhancement in bioavailability study and pharmacodynamics study showed that
      PZ NLC-based transdermal therapeutic system (PNLG-TTS) lowers blood sugar level
      in a sustained pattern for a prolonged period of time as compared to Piosys
      tablet (marketed). The shelf life of the optimized formulation was found to be
      1.83 years. These results clearly provide a lead that above NLCs-based TTS is
      potential controlled release formulation for PZ and could be a promising drug
      delivery system for the treatment of diabetes. 

PMID- 24937379
TI  - Nanosizing of valsartan by high pressure homogenization to produce dissolution
      enhanced nanosuspension: pharmacokinetics and pharmacodyanamic study.
AB  - PURPOSE: The purpose of the present study was to formulate and evaluate
      nanosuspension of Valsartan (VAL), a poorly water soluble and low bioavailable
      drug (solubility of 0.18 mg mL(-1); 23% of oral bioavailability) with the aim of
      improving the aqueous solubility thus the bioavailability and consequently better
      anti-hypertensive activity. METHODS: Valsartan nanosuspension (VAL-NS) was
      prepared using high-pressure homogenization followed by lyophilisation. The
      screening of homogenization factors influencing nanosuspension was done by 3
      factorial, 3-level Box-Behnken statistical design. Model suggested the
      influential role of homogenization pressure and cycles on drug nanosizing. The
      optimized formulation containing Poloxamer(-1)88 (PXM 188) was homogenized for 2
      cycles at 500 and 1000 bar, followed by 5 cycles at 1500 bars. RESULTS: The size
      analysis and transmission electron microscopy showed nanometric size range and
      uniform shape of the nanosuspension. The in vitro dissolution showed an enhanced
      release of VAL from nanosuspension (VAL-NS) compared to physical mixture with PXM
      188. Pharmacodynamic results showed that, oral administration of VAL-NS
      significantly lowered (p <= 0.001) blood pressure in comparison to non
      homogenized VAL (VAL-Susp) in Wistar rat. The level of VAL in rat plasma treated
      with VAL-NS showed significant difference (p <= 0.005) in Cmax (1627.47 +/-
      112.05 ng mL(-1)), Tmax (2.00 h) and AUC0->24 (13279.2 +/- 589.426 ng h mL(-1))
      compared to VAL-Susp that was found to be 1384.73 +/- 98.76 ng mL(-1), 3.00 h and
      9416.24 +/- 218.48 ng h mL(-1) respectively. The lower Tmax value, proved the
      enhanced dissolution rate of VAL. CONCLUSION: The overall results proved that
      newly developed VAL-NS increased the plasma bioavailability and pharmacodyanamic
      potential over the reference formulation containing crude VAL.

PMID- 24937380
TI  - Effects of phonophoresis with gold nanoparticles on oxidative stress parameters
      in a traumatic muscle injury model.
AB  - The aim of this study was to evaluate the effects of therapeutic pulsed
      ultrasound with gold nanoparticles on oxidative stress parameters after traumatic
      muscle injury in Wistar rats. The animals were randomly divided into nine groups
      (n = 6 each): sham (uninjured muscle); muscle injury without treatment; muscle
      injury and treatment with dimethyl sulfoxide (15 mg/kg); muscle injury and
      treatment with gold nanoparticles (27 ug); muscle injury and treatment with
      dimethyl sulfoxide + gold nanoparticles (Plus); muscle injury and therapeutic
      pulsed ultrasound; muscle injury and therapeutic pulsed ultrasound + dimethyl
      sulfoxide; muscle injury and therapeutic pulsed ultrasound + gold nanoparticles;
      and muscle injury and therapeutic pulsed ultrasound + Plus. Gastrocnemius injury
      was induced by a single-impact blunt trauma. Therapeutic pulsed ultrasound (6-min
      application, frequency 1.0 MHz, intensity 0.8 W/cm(2)) was used 2, 12, 24, and 48
      h after trauma. Mitochondrial superoxide generation, lipid peroxidation, and
      protein carbonylation, and the activities of superoxide dismutase, glutathione
      peroxidase, and catalase were evaluated. The increase in the superoxide
      production and TBARS and carbonyl levels observed in the control group after
      muscle damage were reduced in animals exposed to therapeutic pulsed ultrasound
      plus nanoparticles. Similarly, antioxidants enzymes showed a decreased activity
      with the same treatment. Our work suggest that therapeutic pulsed ultrasound +
      dimethyl sulfoxide + gold nanoparticles has beneficial effects on the muscle
      healing process by inducing a decrease in oxidative stress parameters and most
      likely decreasing the deleterious effects of the inflammatory response. 

PMID- 24937381
TI  - Novel flavonoid-based biodegradable nanoparticles for effective oral delivery of
      etoposide by P-glycoprotein modulation: an in vitro, ex vivo and in vivo
      investigations.
AB  - A receptor level interaction of etoposide with P-glycoprotein (P-gp) and
      subsequent intestinal efflux has an adverse effect on its oral absorption. The
      present work is aimed to enhance the bioavailability of etoposide by co
      administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric
      nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were
      optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol
      concentration, PLGA concentration and sonication time. The cytotoxicity studies
      (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide
      loaded nanoparticles (ENP) and etoposide + quercetin dual-loaded nanoparticles
      (EQNP) when compared to that of free etoposide, respectively, and the results
      were further supported by florescent-activated cell sorter studies. The confocal
      imaging of the intestinal sections treated with ENP and EQNP containing
      fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate
      deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited
      a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin.
      The developed loaded nanoparticles have the high potential to enhance the
      bioavailability of the etoposide and sensitize the resistant cells. 

PMID- 24937382
TI  - Preparation oral levofloxacin colon-specific microspheres delivery: in vitro and
      in vivo studies.
AB  - The aim of this study was to prepare levofloxacin-loaded chitosan microspheres
      and to evaluate their in vitro and in vivo characteristics. Glutaraldehyde
      crosslinked microspheres were prepared using a spray-drying method, and
      characterized in terms of the morphological examination, particle size
      distribution, entrapment efficiency, drug loading and in vitro release.
      Pharmacokinetics and colon biodistribution studies were used to evaluate that
      microspheres have more advantage than the conventional formulations. The surface
      morphology of the freeze-dried microspheres were smooth, discrete with a regular
      spherical to near-spherical shape. Size of the microspheres after freeze-drying
      was 4.96 +/- 0.76 MUm and well-distributed. The zeta potential of microspheres
      was -29.3 +/- 2.1 mV. An average drug loading of 9.3 +/- 0.4% and encapsulation
      efficiency of 81.1 +/- 4.7% of levofloxacin microspheres were obtained with the
      optimized preparation parameters. The cumulative release rate of levofloxacin
      microspheres was followed by a sustained release and fitted for classic Higuchi
      kinetic model. In vivo studies showed that chitosan microspheres are thought to
      have the potential to maintain levofloxacin concentration within target ranges
      for a long time, decreasing side effects caused by concentration fluctuation,
      ensuring the efficiency of treatment and improving patient compliance by reducing
      dosing frequency. It also does not cause any harmful or toxic effect in colon and
      rectum as evaluated by histopathologic studies. 

PMID- 24937383
TI  - Synthesis and properties of fluorous benzoquinones and their application in
      deprotection of silyl ethers.
AB  - 1,4-Benzoquinone derivatives bearing trifluoromethyl, perfluorobutyl and
      perfluorohexyl groups were prepared and employed in the deprotection of silyl
      ethers. The fluorous character of these compounds was examined by measuring the
      partition coefficient between the fluorous and organic solvents. The benzoquinone
      derivatives showed significant fluorous character, indicating that they can be
      recovered from the reaction mixtures using a fluorous/organic biphasic system.
      The oxidising ability of the fluorous benzoquinones was estimated by cyclic
      voltammetry, and these compounds were found to be strong oxidisers. The fluorous
      benzoquinones were utilised in the oxidative desilylation of silyl ethers to
      afford the deprotected alcohols in high yield. In addition, the reduced fluorous
      benzoquinones were recovered from the reaction mixtures in good yields using a
      fluorous/organic biphasic system. 

PMID- 24937384
TI  - Effect of Methamidophos on cerebellar neuronal cells.
AB  - Methamidophos is a toxic organophosphorus compound that inhibits
      acetlycholinesterase activity, and induces neurotoxicity. It is a synthetic
      chemical commonly used as pesticides to limit pest damages to cultivated plants.
      Currently, there is serious public health concern over its safety and use due to
      its global nature, persistence and bioaccumulations. We have previously reported
      that methamidophos suppressed thyroid hormone receptor (TR)-mediated
      transcription, but did not dissociate the interaction between TR and its response
      element (thyroid hormone response element; TRE), neither did it interact with
      nuclear cofactors. In the present study, we investigated the effects of
      methamidophos on cerebellar neuronal cells. Using primary cerebellar culture from
      new born rats, We observed that Purkinje cell dendrite arborization were greatly
      impaired in the absence of thyroid hormone (TH), However, low dose methamidophos
      10-6 M did not significantly impair dendrite arborization of cerebellar Purkinje
      cells in the presence of thyroid hormone (TH). However, using granule cell
      reaggregate culture, we observed that low dose methamidophos 10-6 M remarkably
      suppressed granule cell neurite extension in the presence of TH. Taken together,
      our study shows that low dose methamidophos may negatively impact TH-mediated
      cerebellar neuronal cell development and function, and consequently could
      interfere with TH-regulated neuronal events. 

PMID- 24937385
TI  - Cellular and mucosal immune responses in the respiratory tract of Nigerian goats
      following intranasal administration of inactivated Recombinant Mannheimia
      hemolytica bacterine.
AB  - This experiment was conducted to evaluate the cellular and mucosal responses in
      the respiratory tract of Nigerian goats vaccinated intranasally with recombinant
      Mannheimia hemolytica bacterine. Twenty one goats were divided into five groups,
      five goats each in three vaccinated groups while three goats each in two other
      groups serve as positive and negative control. Group A was vaccinated once; group
      B was vaccinated twice at one week interval, and group D at twice at two weeks
      interval. Group C1 were the unvaccinated and challenged, while group C2 were
      unvaccinated and unchallenged. The bronchoalveolar lavage differential counts and
      bronchial associated lymphoid tissue (BALT) responses were measured using Giemsa
      stained thin smear of the cell fraction of the lavage and histomorphometry. ANOVA
      were employed and significance was at p>0.05. The post-challenge macrophage to
      neutrophil (M:N) ratio values of group B goats was the highest and the ratio
      differed from other groups which had much lower M:N values. The exposure in group
      B resulted in significant increase in number and size of BALTs as well as the
      number of lymphocytes in BALT than those of the other groups. This study showed
      that intranasal vaccination of the recombinant Mannheimia hemolytica bacterine
      twice at a week interval was more efficient in inducing strong mucosal and
      defensive cellular responses in the respiratory tract. 

PMID- 24937386
TI  - Interactions of PPAR alpha and GLUT4 in DOCA/salt-induced renal injury in mice.
AB  - Diminished insulin sensitivity is a characteristic feature of various
      pathological conditions such as hypertension and activation of peroxisome
      proliferator activated receptor alpha (PPARalpha) has been shown to enhance
      insulin resistance and reduce capacity for glucose uptake in muscles. The present
      study was designed to evaluate the interactions of PPARalpha and GLUT4 in a model
      of hypertensive renal injury by studying deoxycorticosterone acetate (DOCA)-salt
      induced hypertension in wild-type (WT) and PPARalpha knockout (KO) mice.
      PPARalpha WT and KO mice were uninephrectomized (UNx) and implanted
      subcutaneously DOCA and drank 1% sodium chloride/1% potassium chloride with or
      without a GLUT4 antagonist, indinavir (20 mg/kg/day, s.c) or PPARalpha ligand,
      fenofibrate (100 mg/kg/day, orally). DOCA/salt treatment increased urinary sodium
      excretion and urine volume (p<0.05) in PPARalpha KO mice compared to WT
      littermates. Indinavir increased proteinuria (p<0.01) in DOCA/salt-treated
      PPARalpha KO mice compared to WT littermates but did not affect heart and kidney
      weight index in DOCA/salt KO or WT-treated mice. Urinary sodium excretion (UNaV)
      and urine volume (UV) were increased by indinavir (p<0.01) and fenofibrate
      (p<0.05) in DOCA/salt-treated PPARalpha KO mice compared to WT mice. Urinary
      nitric oxide was greater in both fenofibrate (p<0.05) and indinavir-treated WT
      mice (p<0.05) compared to KO mice. These data suggest that in hypertensive
      nephropathy, GLUT4 probably exerts a renoprotective role that was enhanced with
      the activation of PPARalpha receptors by a mechanism that may be related to
      increased nitric oxide production. 

PMID- 24937387
TI  - Anti-tuberculosis activities of the crude methanolic extract and purified
      fractions of the bulb of Crinum jagus.
AB  - Tuberculosis (TB) is of great public health burden globally especially in
      developing countries of Africa and Asia . Current TB regimen involves multiple
      therapies and of long duration leading to poor patient adherence. There is also
      the challenge of multidrug resistant TB. Hence, there is a need for discovery of
      new anti- TB drugs. This study was designed to investigate the in -vitro activity
      of the crude methanolic extract and chromatographic fractions of the bulb of
      Crinum jagus against Mycobacterium tuberculosis isolates. The extracts were
      screened for anti- TB activity against three different M. tuberculosis isolates
      and a drug susceptible reference strain H37Rv using Lowenstein Jensen (L-J)
      medium and Middlebrook 7H10agar. The crude extract was prepared using soxhlet
      extraction apparatus while the purified fractions were obtained by column
      chromatography. The two media were inoculated with M. tuberculosis strains, after
      which the crude and purified extracts were added. After 4-6 weeks incubation,
      colony forming units were counted and percentage inhibition calculated. The crude
      extract and the purified fractions showed inhibitory activity on all the isolates
      tested including the reference strain. Fraction 3 showed the highest inhibitory
      percentage (86%) among the extracts. At a concentration of 1.0mg/ml, the
      percentage inhibition of fraction 3, rifampicin and isoniazid against M.
      tuberculosis strain 3 were 83%, 95% and 86% in L-J medium respectively while 86%,
      96% and 89% were obtained respectively in Middle brook medium. Results showed
      that the crude methanolic extract and the purified fractions of the bulb of
      Crinum jagus exhibited anti-mycobacterial activity which is an indication of
      promising potential of this plant for the development of anti-tuberculosis agent.

PMID- 24937388
TI  - Effect of ethanolic extract of Carpolobia lutea G. Don (polygalaceae) root on
      learning and memory in CD1 mice.
AB  - Carpolobia lutea, commonly called cattle stick or poor man's candle, is used by
      traditional herbalists in eastern Nigeria to treat 'madness'. It has a reported
      analgesic and anti-nociceptive effect. The effect of its ethanolic root extract
      on learning and memory was investigated. Thirty mice were divided into three
      groups of ten each. One group of mice served as the control and was given normal
      saline (p.o.) while the other two groups were given acute low dose (1500mg/kg,
      p.o.) and high dose (2500mg/kg, p.o.) (LD50 3338.83mg/kg). The effect of the
      extract on cognitive memory was investigated using the Novel Object recognition
      task (NORT) while the effect on visuospatial learning and memory was studied
      using the Morris Water maze (MWM). The results obtained in the NORT show that the
      index of habituation was significantly lower following acute treatment with a low
      dose of C. lutea extract compared to control. However, the index of habituation
      did not differ following treatment with a high dose of C. lutea compared to
      control but it was higher compared to the low dose. Following treatment with a
      low dose of the extract, the index of discrimination was significantly higher
      compared to control. The index of discrimination in the high dose treatment group
      did not differ from control, but it was lower compared to the low dose treatment.
      This indicated that there was improved cognitive memory only in the low dose
      treatment group. In the MWM there was no significant difference in swim latency
      during Acquisition and Reversal training. There also was no significant
      difference in quadrant duration during probe trial. The swim latency during the
      visible platform test showed that all mice used had good visual acuity.
      Therefore, the ethanolic extract of C. lutea root enhanced cognitive memory.
      However it did not affect visuospatial learning and memory. 

PMID- 24937389
TI  - Morphological and neurohistological changes in adolescent rats administered with
      nicotine during intrauterine life.
AB  - Tobacco smoking has been linked to many preventable diseases affecting various
      organs and systems of the body, including the brain. The current study was
      conducted to demonstrate the histological changes observable in the cerebral
      cortex of young Wistar rats exposed to nicotine during gestation. Vaginal
      smearing was conducted for the female Wistar rats to determine their oestrous
      cycle, after which they were exposed to male rats overnight, for mating.
      Pregnancy was confirmed and the pregnant rats were divided into 3 groups based on
      the 3 trimesters (A, B, C), with each group having a control and a treated
      subgroup. The Control Groups (A1, B1, C1) were given 0.1 ml of normal saline i.
      p., while the Treated Groups (A2, B2, C2) received 0.06 mg/kg/0.1 ml of nicotine
      intra-peritoneally. Treatment was for a period of 6 days only within each
      trimester for all subgroups. The pregnant animals were allowed to litter, and at
      postnatal day 35 they were sacrificed. The skull was dissected to expose and
      remove the brain; the temporal and parietal cortices were excised and fixed in 4%
      paraformaldehyde for histological tissue preparation, using cresyl fast violet
      staining techniques. Exposure of the developing brain to nicotine during
      gestation resulted in various degrees of abnormalities in the cytoarchitecture of
      the parietal and temporal cortices of young rats. The gestational period of
      nicotine exposure and specific cortical affectation are important factors to
      consider while investigating neurological abnormalities in offspring of tobacco
      smokers. 

PMID- 24937390
TI  - Comparison of the therapeutic efficacy of double-modality therapy, phonophoresis
      and cryotherapy in the management of musculoskeletal injuries in adult Nigerian
      subjects.
AB  - This study was designed to compare the efficacy of double-modality therapy,
      phonophoresis and cryotherapy in the management of pain among subjects who
      suffered from musculoskeletal injuries (MSIs).Sixty (60) subjects were assigned
      randomly to one of three groups: DMT group (n=20) received cryotherapy and 15%
      methyl salicylate phonophoresis, PHONO group (n=20) received 15% methyl
      salicylate phonophoresis and CRYO group (n=20) received cryotherapy and "sham"
      phonophoresis. Ultrasound at an intensity of 1.5 W/cm2 and frequency of 1MHz was
      used to apply methyl salicylate while intermittent cryotherapy was the mode of
      application. Subjects" pre- and post-treatment pain perception scores (PPS) using
      visual analogue scale (VAS) were assessed and the sessions of treatment in all
      groups were recorded. Treatment was administered on alternate days and discharges
      were made in all groups when subjects were pain free. A total of 275 treatment
      sessions was recorded - 72 (26.2%) in DMT, 105 (38.2%) in PHONO and 98 (35.6%) in
      CRYO group respectively which indicated no significant difference (P>0.05).
      Nineteen (19), thirteen (13) and twelve (12) subjects were pain free in DMT, CRYO
      or PHONO groups respectively after 1 to 5 treatments. The difference in the
      severity of pain was significant (P<0.05) in each group post-treatment which
      suggests that DMT, phonophoresis and cryotherapy were equally effective. The
      study has demonstrated therapeutic efficacy of DMT, but it was not superior to
      the single treatment protocol of phonophoresis or cryotherapy. However, it might
      take fewer sessions in the DMT group to treat and make more than 90% of the
      subjects pain free and fit to return to active performance. 

PMID- 24937391
TI  - Serum levels of copeptin, C-reactive protein and cortisol in different severity
      groups of sickle cell anaemia.
AB  - It is well known that individuals with SCA undergo constant physiological stress
      even, in steady state. However, there is little information on the relationship
      between the severity of sickle cell anaemia (SCA) and serum levels of biomarkers
      of stress. This study therefore determined the serum levels of copeptin, cortisol
      and CRP in adults with SCA in different severity groups. Sixty adults with sickle
      cell anaemia in steady state (27.1+/-6.3 years) and in vaso-occlusive crisis
      (24.9+/-4.9 years) were recruited into this cross-sectional study. Degree of
      severity (mild, moderate or severe) was determined using a scoring system
      incorporating annual number of blood transfusions, crisis and presence of
      anaemia, vaso-occlusive pain and organ complications. Standard methods were used
      for the determination of packed cell volume (PCV), total white blood cell count
      (WBC), blood pressure measurements and anthropometric indices. Serum levels of
      copeptin, cortisol and CRP were determined using ELISA with the ratios calculated
      accordingly. Data obtained were statistically analyzed using the Student's t
      test, Mann Whitney U and Chi-square test as appropriate. P<0.05 was considered
      significant. The mean systolic blood pressure (SBP) and copeptin level were
      significantly higher in subjects with moderate SCA compared with those with mild
      SCA. Similarly SBP, pulse, WBC, copeptin and cortisol were significantly higher
      while body weight was significantly lower in subjects with severe SCA compared
      with subjects with mild SCA. However, WBC and cortisol-to-copeptin ratio were
      significantly higher in subjects with severe SCA compared with subjects with
      moderate SCA. There was progressive rise in serum levels of CRP from mild SCA
      through severe SCA but the differences were not statistically significant. Also,
      proportions of subjects with elevated SBP and WBC were higher than the proportion
      of subjects with lower SBP and WBC in the severe SCA group. Serum levels of
      cortisol, copeptin, and their ratio could differentiate severe SCA from mild or
      moderate SCA. Also, elevated systolic blood pressure and total white blood cell
      count are associated with severe sickle cell anaemia. 

PMID- 24937392
TI  - Nutritional status and dietary pattern of male athletes in Ibadan, South Western
      Nigeria.
AB  - Several factors, including nutritional status and dietary pattern are paramount
      to optimum performance among athletes. Notwithstanding, risky behaviours that
      limit or impair athletic performance are widely prevalent among athletes; these
      include excessive weight reduction and inappropriate dietary practices. This
      study was conducted to provide information on the nutritional status and dietary
      pattern of athletes in Ibadan, Oyo State, Nigeria. This was a cross sectional
      descriptive study, involving 207 athletes aged 17 to 40 years in Ibadan.
      Nutritional status was assessed by anthropometric indices: Body Mass Index (BMI)
      and percentage body fat (%BF). BMI was calculated from weight and height
      measurements and %BF was estimated from the sum of skin-fold thickness at 4 sites
      (triceps, biceps, sub-scapular and supra-iliac skin-folds). Dietary pattern was
      assessed by food habits and food frequency questionnaire. Descriptive and
      inferential statistics were conducted to describe and examine relationships
      between variables. Mean (SD) for variables were: age; 26.09(+/-4.77) years,
      weight; 72.13(+/-0.45) kg, height; 1.74(+/-0.06)m, and BMI; 23.89(+/-3.34)kg/m2.
      Only 4(1.93%) of the participants were underweight, 39(18.84%) were overweight
      and 8(3.86%) obese. Mean (SD) of %BF among overweight athletes was 14.25(+/-3.12)
      and maximum %BF among overweight athletes was 21.2. A strong and positive
      correlation was observed between BMI and %BF and %BF increased with age among
      overweight athletes. About 72% of the athletes skipped meals, 77% drank water or
      sports drinks during sporting activities, about 11% spent less than #40.00 for
      each meal. About 49% ate before sports. Foods most frequently consumed by
      athletes in this study were meat, fish, roots/tubers, cereals, vegetables and
      fruits. Milk and legumes were less frequently consumed by these athletes. Most of
      these athletes had nutritional status adequate for their sport activity. With
      regards to food habits, most of these athletes performed poorly in frequency of
      meals intake but did considerably well in intake of fluids. With regards to
      dietary pattern, sources of daily intakes comprised of mostly of meats, fish,
      roots and tubers, cereals and vegetables. 

PMID- 24937393
TI  - Effect of honey consumption on intestinal motility in male albino rats.
AB  - This study investigated the effects of honey on intestinal motility and transit
      using twenty (20) male albino rats of Wistar strain weighing 210-220g. The rats
      were randomly grouped into control and honey-fed (test) groups of ten (10) rats
      each. The control group was fed on normal rat chow ( Pfizer Company, Nigeria )
      and water while the test group was fed on rat feed, water and honey ( 1 ml of
      honey to every 10 ml initial drinking water daily) for twenty two (22) weeks
      after which the rats were starved over night before the experiment and sacrificed
      by stunning. Laparatomy was immediately performed, proximal and distal portions
      of the intestine identified, cut and put in aerated tyrode solution. Cut sections
      of the ileum (2-3cm) were mounted on organ bath instrument for motility
      experiment with varying concentrations of acetylcholine and carbachol.
      Contractions were recorded as well as the intestinal transit in each group and
      lengths of intestine with total mean values calculated. Results obtained showed
      that honey significantly decreased (p<0.01 ) intestinal transit in the test group
      (21.15+/-0.75 ) compared with the control group ( 35.96+/-1.15); decreased
      intestinal motility in the test group compared with the control and caused
      significant percentage reduction of intestinal motility with varied
      concentrations of acetylcholine and carbachol in the test group ( Ach-75.00+/
      0.75%; Carbachol-79.00+/-0.28%) compared with the control group (Ach-62.00+/
      0.39%; Carbachol-51.00+/-0.39%). In conclusion, unprocessed Nigerian honey
      decreased intestinal transit, caused intestinal smooth muscle inhibition and
      motility and reduced sensitivity of gastrointestinal tract to cholinergic agents.

PMID- 24937394
TI  - Coffee consumption attenuates insulin resistance and glucose intolerance in rats
      fed on high-sucrose diet.
AB  - Several epidemiological evidences indicate that consumption of coffee is
      associated with a lower risk of type 2 diabetes mellitus (T2DM) however; there is
      dearth of experimental data to support these observations. Given that
      associations do not necessarily infer causality, the present study was designed
      to investigate the effect of coffee consumption on glucose regulation, T2DM and
      the probable mechanisms of action, using an animal model. The effect of coffee (2
      fold dilution) by oral gavage on normal and high sucrose-solution (HSS) fed (30 %
      w/v) rats was evaluated. The results showed that consumption of coffee
      significantly increase glucose tolerance and insulin sensitivity (p<0.05) along
      with significant improvement in SOD and GSH activities. In addition, lipid
      indices such as TG and LDL as well as the lipid peroxidation marker (MDA) were
      markedly reduced (p<0.05) in rats fed with coffee compared with that of the HSS
      fed rats. These findings suggest that coffee consumption improves insulin
      sensitivity, glucose tolerance in HSS-fed rat possibly via inhibition of
      oxidative stress. 

PMID- 24937395
TI  - Molecular diagnosis of MDR-TB using GenoType MTBDRplus 96 assay in Ibadan,
      Nigeria.
AB  - Multidrug resistant Mycobacterium tuberculosis (MDR-TB) is of great public health
      importance worldwide. This three month laboratory- based study (1st September
      30th November, 2011) was carried out at the TB laboratories of the University
      College Hospital, Ibadan, Nigeria to determine the magnitude of MDR-TB using
      molecular based GenoType MTBDRplus 96 assay. Two sputum samples were collected
      from each subject. These were processed using Ziehl -Neelsen (ZN) reagents. The
      sputa were cultured on Loewenstein-Jensen egg -based medium and incubated at 370C
      for eight weeks. Mycobacterium tuberculosis complex (MTBC) was confirmed by
      colonial morphology and repeat ZN staining. All the Acid-fast bacill (AFB)
      positive smears and culture positive isolates were tested for genetic
      identification and drug susceptibility testing (DST) using PCR- based GenoType
      MTBDRplus 96 assay (HAINs Lifesciences, GmbH, Nehren, Germany) according to
      manufacturers' instructions. Of the 68 samples processed, 11 (16.2%) were AFB
      positive while six (8.8%) were positive for culture. Eleven (64.7%) out of the 17
      samples tested for genetic identification were MTBC while six were Non
      Tuberculosis Mycobacteria (NTM). All NTM were from AFB positive sputum while none
      was from culture positive isolates. Of the six culture isolates tested for DST,
      three (33.3%) were susceptible to isoniazid and rifampicin; one (16.7%) showed
      mono-resistance to isoniazid while two (30.0%) were resistant to the two drugs.
      This study shows that MDR-TB is present in Ibadan. There is a need to make DST
      diagnostic facilities more available and accessible in Nigeria. 

PMID- 24937396
TI  - Anti-ulcerogenic mechanism of magnesium in indomethacin induced gastric ulcer in
      rats.
AB  - The gastric mucosa is continuously exposed to various agents like food
      condiments, spices, alcohol, acids and drugs, some of which are implicated in the
      pathogenesis of gastric ulcer. Magnesium compounds commonly used as laxatives and
      antacids have been reported to prevent ulcer formation but the mechanisms
      underlying this potential is unknown. This study therefore seeks to evaluate the
      gastro-protective mechanism of magnesium in the stomach through its effect on the
      parietal and mucus cells. Thirty-six male albino rats divided into 6 groups of 6
      rats each were used. Group 1 was control, Group 2 was ulcer induced and
      untreated, Group 3 was treated with 500mg/kg b.w magnesium alone, Group 4 was pre
      treated with 500mg/kg b.w magnesium before inducing ulcer, Group 5 was pre
      treated with 500mg/kg b.w magnesium and 20mg/kg omeprazole 4 hours before
      inducing ulcer, Group 6 was treated with 20mg/kg omeprazole 4 hours before
      inducing ulcer. Animals were sacrificed 6 hours after ulcer induction and their
      stomachs were removed for ulcer scoring and histological analysis. A significant
      reduction was observed in the ulcer scoring of magnesium pre-treated ulcerated
      rats (9.4+/-0.8) compared with ulcerated untreated (20.8+/-0.9) groups. Parietal
      cell count of magnesium pre treated ulcerated group significantly decreased
      (169.7+/-18.9) compared with ulcerated untreated group (310.5+/-34.7). Mucous
      cell count of magnesium pre-treated ulcerated group (264.6+/-8.3) significantly
      increased compared with ulcerated untreated group (170.0+/-17.7). This study
      shows that magnesium possesses anti-ulcerogenic properties due to its ability to
      reduce the number of parietal cell and increase mucous cell counts. 

PMID- 24937397
TI  - Pre-clinical grades predict clinical performance in the MBBS stage II examination
      at the University of the West Indies, Mona Campus.
AB  - In the preclinical sciences, statistically significant predictive values have
      been reported between the performances in one discipline and the others,
      supporting the hypothesis that students who perform well in one discipline were
      likely to perform well in the other disciplines. We therefore decided to conduct
      a retrospective study to investigate the predictive effects of preclinical
      subjects on clinical subjects from 87 students of The University of the West
      Indies (UWI), Mona Campus who took the MBBS Stage II examination at various times
      between May 2000 and May 2002. The grade in Pathology was significantly predicted
      by scores in Anatomy and Pharmacology; Medicine by Physiology and Pharmacology
      scores; Surgery by Anatomy and Social and Preventive Medicine scores; while, the
      Obstetrics and Gynecology grade was predicted by the Anatomy score. The results
      support the hypothesis that the scores in some preclinical subjects can predict
      the performance in specific clinical subjects, which could be interpreted to
      suggest that poor performance in specific preclinical disciplines could be a
      warning sign of future poor performance in the related clinical disciplines. 

PMID- 24937398
TI  - Impact of alcohol consumption and cigarette smoke on renal function and select
      serum elements in female subjects using combined oral contraceptive.
AB  - Drugs and life style choices such as alcohol consumption and smoking are capable
      of independently altering levels of essential trace elements as well as tissue or
      organ function. The purpose of the study is to determine how differences in
      degree of exposure to cigarette smoke and alcohol consumption will alter serum
      magnesium (Mg), Cobalt (Co) and Manganese (Mn) levels in female subjects using
      combined oral contraceptives. Thirty female subjects who have used combined oral
      contraceptive for at least 5 years as well as 30 age-matched control women who
      are using rhythm method as birth control method were recruited from drinking
      joints/bars by random sampling technique. Serum trace element concentrations were
      determined using atomic absorption spectrometry and K+, Na+, albumin, globulin,
      total protein, urea and creatinine were also determined. Data obtained were
      analyzed using Student't' test, Pearson's correlation coefficient and
      Multivariate Analysis of Variance (MANOVA). Na+ was significantly higher in
      combined oral contraceptive users compared with controls (p<0.05), whereas Mg was
      decreased (p<0.05). Co, Mn, urea, creatinine, total protein, albumin, globulin,
      K+ were not significantly different in combined oral contraceptive users compared
      with the controls (p>0.05). MANOVA results revealed that binge drinkers/smokers
      group recorded a significant lower (p<0.05) magnesium level than the passive
      smokers/social drinkers group and controls. The results of this study suggest
      that subjects using combined oral contraceptive, consuming alcohol and exposed to
      cigarette smoke may be at greater risks of diseases linked with magnesium
      depletion. 

PMID- 24937399
TI  - Relationship between anthropometric and haematological parameters among third
      trimester pregnant women in Sokoto State, Northwest Nigeria.
AB  - The pregnancy state in a woman's life is a unique state in terms of the desirable
      physiological changes and the exciting reversal of the changes soon after the
      termination of the pregnancy. It is considered essential that to guarantee a good
      feto-maternal outcome the attainment of optimum anthropometric and haematological
      parameters are key. Our study assessed the anthropometric and haematological
      changes and also looked at the relationship that exists between these parameters
      among pregnant women.We carried out a cross-sectional descriptive study which
      considered 160 apparently healthy, singleton, third trimester pregnant women
      attending ANC at the State Specialist Hospital and 58 apparently healthy non
      pregnant controls sourced from the Sokoto metropolis population. Each subject or
      control enrolled was contacted 3 times at 2 weekly intervals. And at each
      occasion they are assessed for changes in the anthropometric and haematological
      parameters. The response rate was 93.6% (3 pregnants and 11 controls were loss to
      follow up). The pregnant and control subgroups mean ages were 28.02 +/- 6.81
      years and 26.89 +/- 5.84 years respectively (p = 0.265). Weekly weight gains of
      0.48kg among the pregnant sub-group against 0.13kg obtained in the control group
      were recorded. BMI increase of about 0.19kg/m2 per week among the pregnant sub
      group and only 0.05kg per week in the controls. 95% of the distribution of
      pregnant sub-group has haemoglobin and haematocrit of >=8.9g/dL and >=26%
      respectively. Among the pregnant sub-group, mean weekly haemoglobin and
      haematocrit drop of 0.24g/dL and 0.74% were respectively recorded. A steady rise
      in WBC was recorded but platelets counts dropped at an average of 5.04 x 103 /MUL
      per week. A positive correlation between BMI and haemoglobin levels was observed
      (r > 0 and p < 0.05). No particular regularity in the relationship between BMI
      and WBC was noticed. We conclude that there was optimum weight gain and good
      haematological indices for those with good BMI during the third trimester of
      pregnancy. There was a positive correlation between BMI and plasma haemoglobin
      level but WBC showed no particular relationship with the anthropometric changes.
      We therefore, recommend that good education to improve the socio- economic
      wellbeing of the girl-child be encouraged to boost self sufficiency for better
      weight gains and to facilitate access to good healthcare so that the ideal
      anthropometric and haematological parameters can be achieved during pregnancy to
      guarantee good feto-maternal outcome. 

PMID- 24937401
TI  - Horizontal eddy energy flux in the world oceans diagnosed from altimetry data.
AB  - During the propagation of coherent mesoscale eddies, they directly or indirectly
      induce many effects and interactions at different scales, implying eddies are
      actually serving as a kind of energy carrier or energy source for these eddy
      related dynamic processes. To quantify this dynamically significant energy flow,
      the multi-year averaged horizontal eddy energy fluxes (EEFs) were estimated by
      using satellite altimetry data and a two-layer model based on hydrographic
      climatology. There is a strong net westward transport of eddy energy estimated at
      the mean value of ~13.3 GW north of 5 degrees N and ~14.6 GW at the band 5
      degrees S ~ 44 degrees S in the Southern Hemisphere. However, poleward of 44
      degrees S east-propagating eddies carry their energy eastward with an averaged
      net flux of ~3.2 GW. If confirmed, it would signify that geostrophic eddies not
      only contain the most of oceanic kinetic energy (KE), but also carry and spread a
      significant amount of energy with them.

PMID- 24937402
TI  - Neglected tropical diseases and omics science: proteogenomics analysis of the
      promastigote stage of Leishmania major parasite.
AB  - Among the neglected tropical diseases, leishmaniasis is one of the most
      devastating, resulting in significant mortality and contributing to nearly 2
      million disability-adjusted life years. Cutaneous leishmaniasis is a debilitating
      disorder caused by the kinetoplastid protozoan parasite Leishmania major, which
      results in disfiguration and scars. L. major genome was the first to be sequenced
      within the genus Leishmania. Use of proteomic data for annotating genomes is a
      complementary approach to conventional genome annotation approaches and is
      referred to as proteogenomics. We have used a proteogenomics-based approach to
      map the proteome of L. major and also annotate its genome. In this study, we
      searched L. major promastigote proteomic data against the annotated L. major
      protein database. Additionally, we searched the proteomic data against six-frame
      translated L. major genome. In all, we identified 3613 proteins in L. major
      promastigotes, which covered 43% of its proteome. We also identified 26 genome
      search-specific peptides, which led to the identification of three novel genes
      previously not identified in L. major. We also corrected the annotation of N
      termini of 15 genes, which resulted in extension of their protein products. We
      have validated our proteogenomics findings by RT-PCR and sequencing. In addition,
      our study resulted in identification of 266 N-terminally acetylated peptides in
      L. major, one of the largest acetylated peptide datasets thus far in Leishmania.
      This dataset should be a valuable resource to researchers focusing on neglected
      tropical diseases.

PMID- 24937403
TI  - COX-2 inhibition improves retinal function in rats' ischemic eyes.
AB  - PURPOSE: Retinal ischemia is a relatively simple model for studies in
      pharmacological neuroprotective intervention. The role of cyclooxygenase (COX)
      enzymes in ischemic insult has been variously shown to either increase or
      decrease ischemic damage. The purpose of this study was to assess the role of COX
      1 and COX-2 in rat retinal ischemic functional damage. METHODS: Ischemia was
      achieved by elevating intraocular pressure for 60 min. White flash
      electroretinogram (ERG) was recorded by contact lens electrodes containing an
      integral light emitting diode source. ERG was recorded on post-ischemia (PI) days
      1 (baseline), 1, 3, and 7. The b-wave amplitude, b-wave implicit time, and
      oscillatory potentials (OPs) were analyzed. The expression of COX-2 and HSP70i
      was assessed by Western analysis on day 1 PI. RESULTS: Ischemia caused
      attenuation of OPs, a decrease in the b-wave amplitude, and an increase in b-wave
      implicit time, accompanied by the increased expression of COX-2 and HSP70i
      proteins. Selective COX-2 inhibition markedly increased b-wave amplitude and
      enhanced retinal HSP70i induction, whereas COX-1 or nonselective and irreversible
      inhibition of both COX isoenzymes did not affect the retinal function or the
      expression of these proteins. High-dose aspirin prevented partial recovery from
      ischemic damage. Administration of a synthetic PGF2alpha analog, or a
      lipoxygenase inhibitor, had little effect on ischemic damage, but affected
      nonischemic ERG. CONCLUSIONS: COX-2 appears to mediate some of the ischemic
      retinal functional damage, possibly by inhibiting the induction of HSP-70i. We
      propose that selective COX-2 inhibitors may be useful in pathological conditions
      involving ischemic retinal insult.

PMID- 24937404
TI  - Aminoadamantanes versus other antiviral drugs for chronic hepatitis C.
AB  - BACKGROUND: Hepatitis C virus infection affects around 3% of the world population
      or approximately 160 million people. A variable proportion (5% to 40%) of the
      infected people develop clinical symptoms. Hence, hepatitis C virus is a leading
      cause of liver-related morbidity and mortality with hepatic fibrosis, end-stage
      liver cirrhosis, and hepatocellular carcinoma as the dominant clinical sequelae.
      Combination therapy with pegylated (peg) interferon-alpha and ribavirin achieves
      sustained virological response (that is, undetectable hepatitis C virus RNA in
      serum by sensitivity testing six months after the end of treatment) in
      approximately 40% to 80% of treated patients, depending on viral genotype.
      Recently, a new class of drugs have emerged for hepatitis C infection, the direct
      acting antivirals, which in combination with standard therapy or alone can lead
      to sustained virological response in 80% or more of treated patients.
      Aminoadamantanes, mostly amantadine, are antiviral drugs used for the treatment
      of patients with chronic hepatitis C. We have previously systematically reviewed
      amantadine versus placebo or no intervention and found no significant effects of
      the amantadine on all-cause mortality or liver-related morbidity and on adverse
      events in patients with hepatitis C. Overall, we did not observe a significant
      effect of amantadine on sustained virological response. In this review, we
      systematically review aminoadamantanes versus other antiviral drugs. OBJECTIVES:
      To assess the beneficial and harmful effects of aminoadamantanes versus other
      antiviral drugs for patients with chronic hepatitis C virus infection by
      conducting a systematic review with meta-analyses and trial sequential analyses
      of randomised clinical trials. SEARCH METHODS: The Cochrane Hepato-Biliary Group
      Controlled Trials Register (1996 to December 2013), the Cochrane Central Register
      of Controlled Trials (CENTRAL) (Issue 11 of 12, 2013), MEDLINE (1946 to December
      2013), EMBASE (1974 to December 2013), Science Citation Index EXPANDED (1900 to
      December 2013), the WHO International Clinical Trials Registry Platform
      (www.who.int/ictrp), Google Scholar, and Eudrapharm up to December 2013.
      Furthermore, full text searches were conducted until December 2013. SELECTION
      CRITERIA: Randomised clinical trials assessing aminoadamantanes in participants
      with chronic hepatitis C virus infection. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data. RevMan Analysis was used for statistical
      analysis of dichotomous data using risk ratio (RR) with 95% confidence intervals
      (CI). Methodological domains were used to assess the risk of systematic errors
      ('bias'). We used trial sequential analysis to assess risk of random errors
      ('play of chance'). MAIN RESULTS: Six randomised clinical trials with 581
      participants with chronic hepatitis C were included. All trials had high risk of
      bias. The included trials compared amantadine versus other antiviral drugs:
      ribavirin, mycophenolate mofetil, interferon-alpha, or interferon-gamma. Standard
      antiviral therapy (interferon-alpha, interferon-alpha plus ribavirin, or peg
      interferon alpha) was administered equally to the intervention and the control
      groups in five trials, depending on when the trial was conducted. Four trials
      compared amantadine versus ribavirin. There were no deaths or liver-related
      morbidity in the two intervention groups (0/216 (0%) versus 0/211 (0%); 4 trials;
      very low quality of the evidence). The lower estimated risk for (serious) adverse
      events leading to treatment discontinuation with amantadine was imprecise (RR
      0.56, 95% CI 0.27 to 1.16; based on 10/216 (5%) versus 18/211 (9%) participants
      in 4 trials; very low quality of the evidence). There were more participants with
      failure of sustained virological response in the amantadine group than in the
      ribavirin group (206/216 (96%) versus 176/211 (84%); RR 1.14, 95% CI 1.07 to
      1.22, 4 trials; low quality of the evidence). Amantadine versus ribavirin more
      often failed to achieve end-of follow-up biochemical response (41/46 (89%) versus
      31/46 (67%); RR 1.31, 95% CI 1.05 to 1.63; 2 trials; very low quality of the
      evidence). One trial compared amantadine versus mycophenolate mofetil. There were
      no significant differences between the two treatment groups, except that
      amantadine was inferior to mycophenolate mofetil regarding the outcome failure to
      achieve end-of treatment virological response (low quality of evidence). One
      trial each compared amantadine versus interferon-alpha or interferon-gamma. Both
      comparisons showed no significant differences in the treatment outcomes (very low
      quality of the evidence). The observed effects could be due to real effects,
      systematic errors (bias), or random errors (play of chance). This possible
      influence on the observed effect by play of chance is due to the fact that trial
      sequential analyses could not confirm our findings. We were not able to perform
      meta-analyses on failure of histological improvement and quality of life due to
      lack of valid data in all trial comparisons. AUTHORS' CONCLUSIONS: This
      systematic review has identified evidence of very low quality for the key
      outcomes of all-cause mortality or liver-related morbidity and adverse events in
      people with chronic hepatitis C when treated with amantadine compared with
      ribavirin, mycophenolate, interferon-alpha, or interferon-gamma. The timeframe
      for measuring the composite outcome was insufficient in the included trials.
      There was low quality evidence that amantadine led to more participants who
      failed to achieve sustained virological response compared with ribavirin. This
      observation may be real or caused by systematic errors (bias), but it does not
      seem to be caused by random error (play of chance). Due to the low quality of the
      evidence, we are unable to determine definitively whether amantadine is less
      effective than other antivirals in patients with chronic hepatitis C. As it
      appears less likely that future trials assessing amantadine or potentially other
      aminoadamantanes for patients with chronic hepatitis C would show strong
      benefits, it is probably better to focus on the assessments of other direct
      acting antiviral drugs. We found no evidence assessing other aminoadamantanes in
      randomised clinical trials in order to recommend or refute their use.

PMID- 24937405
TI  - Conserved glycine 232 in the ligand channel of ba3 cytochrome oxidase from
      Thermus thermophilus.
AB  - Knowing how the protein environment modulates ligand pathways and redox centers
      in the respiratory heme-copper oxidases is fundamental for understanding the
      relationship between the structure and function of these enzymes. In this study,
      we investigated the reactions of O2 and NO with the fully reduced G232V mutant of
      ba3 cytochrome c oxidase from Thermus thermophilus (Tt ba3) in which a conserved
      glycine residue in the O2 channel of the enzyme was replaced with a bulkier
      valine residue. Previous studies of the homologous mutant of Rhodobacter
      sphaeroides aa3 cytochrome c oxidase suggested that the valine completely blocked
      the access of O2 to the active site [Salomonsson, L., et al. (2004) Proc. Natl.
      Acad. Sci. U.S.A. 101, 11617-11621]. Using photolabile O2 and NO carriers, we
      find by using time-resolved optical absorption spectroscopy that the rates of O2
      and NO binding are not significantly affected in the Tt ba3 G232V mutant.
      Classical molecular dynamics simulations of diffusion of O2 to the active site in
      the wild-type enzyme and G232V mutant show that the insertion of the larger
      valine residue in place of the glycine appears to open up other O2 and NO
      exit/entrance pathways that allow these ligands unhindered access to the active
      site, thus compensating for the larger valine residue. 

PMID- 24937406
TI  - The 2011 survey on hypertensive disorders of pregnancy (HDP) in China:
      prevalence, risk factors, complications, pregnancy and perinatal outcomes.
AB  - Hypertensive disorders of pregnancy (HDP) are a group of medical complications in
      pregnancy and also a risk factor for severe pregnancy outcomes, but it lacks a
      large-scale epidemiological investigation in recent years. This survey represents
      a multicenter cross-sectional retrospective study to estimate the prevalence and
      analyze the risk factors for HDP among the pregnant women who had referred for
      delivery between January 1st 2011 and December 31st 2011 in China Mainland. A
      total of 112,386 pregnant women were investigated from 38 secondary and tertiary
      specialized or general hospitals randomly selected across the country, of which
      5,869 had HDP, accounting for 5.22% of all pregnancies. There were significant
      differences in the prevalence of HDP between geographical regions, in which the
      North China showed the highest (7.44%) and Central China showed the lowest
      (1.23%). Of six subtypes of HDP, severe preeclampsia accounted for 39.96%,
      gestational hypertension for 31.40%, mild preeclampsia for 15.13%, chronic
      hypertension in pregnancy for 6.00%, preeclampsia superimposed on chronic
      hypertension for 3.68% and eclampsia for 0.89%. A number of risk factors for HDP
      were identified, including twin pregnancy, age of >35 years, overweight and
      obesity, primipara, history of hypertension as well as family history of
      hypertension and diabetes. The prevalence of pre-term birth, placental abruption
      and postpartum hemorrhage were significantly higher in women with HDP than those
      without HDP. The possible risk factors confirmed in this study may be useful for
      the development of early diagnosis and appropriate treatment of HDP. 

PMID- 24937407
TI  - Biodiversity mapping in a tropical West African forest with airborne
      hyperspectral data.
AB  - Tropical forests are major repositories of biodiversity, but are fast
      disappearing as land is converted to agriculture. Decision-makers need to know
      which of the remaining forests to prioritize for conservation, but the only
      spatial information on forest biodiversity has, until recently, come from a
      sparse network of ground-based plots. Here we explore whether airborne
      hyperspectral imagery can be used to predict the alpha diversity of upper canopy
      trees in a West African forest. The abundance of tree species were collected from
      64 plots (each 1250 m(2) in size) within a Sierra Leonean national park, and
      Shannon-Wiener biodiversity indices were calculated. An airborne spectrometer
      measured reflectances of 186 bands in the visible and near-infrared spectral
      range at 1 m(2) resolution. The standard deviations of these reflectance values
      and their first-order derivatives were calculated for each plot from the c. 1250
      pixels of hyperspectral information within them. Shannon-Wiener indices were then
      predicted from these plot-based reflectance statistics using a machine-learning
      algorithm (Random Forest). The regression model fitted the data well (pseudo-R(2)
      = 84.9%), and we show that standard deviations of green-band reflectances and
      infra-red region derivatives had the strongest explanatory powers. Our work shows
      that airborne hyperspectral sensing can be very effective at mapping canopy tree
      diversity, because its high spatial resolution allows within-plot heterogeneity
      in reflectance to be characterized, making it an effective tool for monitoring
      forest biodiversity over large geographic scales.

PMID- 24937408
TI  - Synthesis and electrochemical properties of porphycene-diketopyrrolopyrrole
      conjugates.
AB  - The selective iodination of 2,7,12,17-tetrahexylporphycene 1 was successfully
      accomplished by using N-iodosuccinimide in the presence of activators to give 3
      iodoporphycene 2 and 3,13-diiodoporphycene 3a. These iodinated porphycenes can be
      used as the substrates for palladium-catalyzed coupling to prepare porphycene
      diketopyrrolopyrrole conjugates in two steps. The connection of the
      diketopyrrolopyrrole units to porphycenes broadened their absorption spectra and
      increased the intensity of the Q-bands due to the electronic interactions between
      the porphycene and diketopyrrolopyrrole moieties. 

PMID- 24937411
TI  - Introduction.

PMID- 24937410
TI  - Nanoscale analysis of a functionalized polythiophene surface by adhesion mapping.
AB  - Functionalized ethylenedioxythiophene (EDOT) monomers, hydroxymethyl EDOT (EDOT
      OH), and zwitterionic phosphorylcholine EDOT (EDOT-PC) were electropolymerized to
      prepare the homopolymers poly(EDOT-OH) and poly(EDOT-PC), and mixtures of these
      monomers were used to produce the copolymer poly(EDOT-OH)-co-poly(EDOT-PC). Force
      extension-curve-based atomic force microscopy (AFM) was utilized to analyze the
      surfaces of the films. The PEDOT-OH film yielded force-extension curves for short
      stretching, and the PEDOT-PC film yielded curves for long stretching. A dendron
      modified AFM tip with anthracene groups tethered at the end resulted in adhesion
      maps with the highest contrast. The analytical data for the copolymer films
      correlated with the corresponding monomer composition, and the maps revealed that
      the average size for the copolymer nanodomains ranged from 10-14 nm. This
      approach can be applied to studies aimed at understanding the surface structure
      of other relevant polymers and copolymers at the nanoscale level. 

PMID- 24937409
TI  - Silver nanoparticles: Synthesis methods, bio-applications and properties.
AB  - Silver nanoparticles size makes wide range of new applications in various fields
      of industry. Synthesis of noble metal nanoparticles for applications such as
      catalysis, electronics, optics, environmental and biotechnology is an area of
      constant interest. Two main methods for Silver nanoparticles are the physical and
      chemical methods. The problem with these methods is absorption of toxic
      substances onto them. Green synthesis approaches overcome this limitation. Silver
      nanoparticles size makes wide range of new applications in various fields of
      industry. This article summarizes exclusively scalable techniques and focuses on
      strengths, respectively, limitations with respect to the biomedical applicability
      and regulatory requirements concerning silver nanoparticles. 

PMID- 24937412
TI  - Essential considerations when choosing a modern antidepressant.
AB  - The man-years of disability produced by depression in industrialised nations is
      second only to that caused by ischaemic heart disease. One in ten patients seen
      by a primary care physician is suffering from depressive symptoms (but neither of
      them may recognise it). Depression is clearly a major health problem, which can,
      however, be successfully treated by modern antidepressants in the overwhelming
      majority of cases. The problem for the primary care physician is not whether to
      treat but how to treat major depression. The increasing number of antidepressants
      from different families with different mechanisms has become an embarrassment of
      riches. When choosing an antidepressant, efficacy, adverse effects, safety in
      overdose, potential drug interactions and withdrawal effects are among the
      principal criteria. Although all antidepressants may appear to be equivalent in
      efficacy, in more severely depressed patients it has been demonstrated that dual
      action antidepressants, acting on both serotonin and noradrenaline, have superior
      efficacy to compounds acting on a single neurotransmitter. In addition certain
      types of depressive symptoms may respond better to one antidepressant than to
      another. The importance of adverse effects goes beyond patient safety and comfort
      and has a major influence on efficacy. If, due to adverse effects, an
      antidepressant is prescribed at sub-optimal doses or the patient is not
      compliant, even the most effective antidepressant will perform badly. The risk of
      suicide is inherent to depression, and to prescribe a drug which if taken in
      overdose can be fatal if used in a suicide attempt, is clearly unacceptable.
      Similarly certain antidepressants have a far greater potential for interactions
      with other drugs with potentially toxic effects and should be avoided in patients
      taking several medications. Applying these criteria globally will not designate a
      single "best antidepressant" but consideration of the importance of each criteria
      for an individual patient will help the clinician to find the antidepressant best
      adapted to each patient. 

PMID- 24937413
TI  - Evidence-based prescribing of antidepressants.
AB  - Modern antidepressants are required to undergo extensive clinical investigation
      before their commercialisation is authorised, and this provides the basis for the
      "evidence-based recommendations" for their use. Because of the rigorous
      methodology required in formal clinical trials in order to establish efficacy,
      the population studied and the conditions of use of a treatment are likely to
      differ substantially from those encountered in everyday clinical practice. There
      is limited opportunity in clinical trials for casual observation of the effects
      of the drug, its efficacy in patients with co-morbid disorders, or its use
      outside of the strict indication for which the compound seeks a licence. The
      observations, case studies, open trials and small comparative trials that are
      conducted on an antidepressant after it has been launched can provide important
      information. The less rigorous methodology is to some extent compensated by their
      relevance to everyday prescribing and their openness to chance discoveries. They
      can provide complementary information on responder characteristics and acceptance
      of side effects and can suggest potential conditions and indications not
      originally foreseen. This body of data can be referred to as "prescribing-based
      evidence". The obvious complementarity of these two bodies of information is
      illustrated by reference to the serotonin and noradrenaline reuptake inhibitor
      (SNRI), milnacipran, which has been the subject of intense post-marketing study,
      especially in Japan. The newly discovered efficacy of milnacipran in chronic
      pain, both associated with depression and in conditions such as fibromyalgia, is
      an example of the extended understanding that can be obtained by such studies. 

PMID- 24937414
TI  - Five years experience of prescribing milnacipran: An interview with Didier Papeta
      (Head of Psychiatry, General Military Hospital, Brest, France).
AB  - The serotonin and noradrenaline reuptake inhibitor (SNRI), milnacipran, has been
      available in France for over 5 years. Although many of the published clinical
      trials were, at least partially, carried out in France, there has been little
      feedback in the medical literature concerning the everyday use of milnacipran in
      this country. In contrast to the tradition in some countries, the publication of
      case reports in French medical journals is not common. In order to get a feedback
      from day-to-day use of a compound it is therefore necessary to carry out use
      surveys which are expensive and time-consuming. In the absence of such surveys
      personal opinions forged over several years by extensive prescribers of a
      compound can give valuable insight, albeit with the risks of bias and of being
      non-representative. 

PMID- 24937415
TI  - Milnacipran in the treatment of elderly depressed patients including a case of
      interferon-induced depression.
AB  - Elderly patients represent a particularly fragile patient group that requires
      highly effective but extremely well tolerated antidepressants. Two cases are
      reported showing that the serotonin and noradrenaline reuptake inhibitor,
      milnacipran, is both effective and well tolerated. One case is the first reported
      in which milnacipran is shown to effectively reduce interferon-induced depressive
      symptoms. 

PMID- 24937416
TI  - Efficacy of milnacipran for glossodynia patients.
AB  - Pain and depression are thought to arise from a common neurochemical dysfunction
      at the level of noradrenergic and serotonergic neurons, and antidepressants are
      used to treat chronic pain. The dual action tricyclic antidepressants are more
      potent in relieving pain than the selective serotonin reuptake inhibitors.
      Glossodynia is chronic pain and burning sensation in the tongue often associated
      with depression. Patients suffering from glossodynia were treated with the
      serotonin and noradrenaline reuptake inhibitor, milnacipran, which has been
      recently launched in Japan. Milnacipran was found to be effective in the relief
      of the chronic glossodynia and well tolerated. 

PMID- 24937417
TI  - New treatment of depression in Parkinson's disease.
AB  - Anhedonia and apathy are the main symptoms of depression generally associated
      with Parkinson's disease. Tricyclic antidepressants (TCA) and selective serotonin
      reuptake inhibitors (SSRI) have been used to treat depression associated with
      Parkinson's disease. However, the poor tolerance of TCA and the worsening of the
      motor function by SSRI have favoured other therapeutic approaches. Some studies
      have shown that agents stimulating the noradrenergic system were able to improve
      depression in parkinsonian patients. The serotonin and noradrenaline reuptake
      inhibitor, milnacipran, has become available recently in Japan. The aim of this
      study was to investigate the potential of milnacipran to alleviate depressive
      symptoms in patients suffering from Parkinson's disease, particularly the
      symptoms anhedonia and apathy. 

PMID- 24937418
TI  - Expression of gene, protein and immunohistochemical localization of the estrogen
      receptor isoform ERalpha1 in male rainbow trout lymphoid organs; indication of
      the role of estrogens in the regulation of immune mechanisms.
AB  - In vertebrates, estrogens act on the reproductive system but also affect the
      functioning of non-reproductive tissues such as the immune system. In teleost
      fish, effects of estrogens and xenoestrogens have been reported extensively, but
      the available information on targeted tissues and cells is still scarce.
      Moreover, a better knowledge of the distinct ER subtypes is required to find out
      the mechanistic pathways by which estrogen compounds are able to disrupt
      endogenous estrogen signaling in fish immunity. The present study aimed at
      characterizing, in male rainbow trout juveniles, multi-tissue gene expression
      pattern of one isoform of estrogen receptor (ER), ERalpha1, at the mRNA and
      protein levels. The mRNA levels for ERalpha1 were measured in various lymphoid
      organs by real-time RT-PCR and ERalpha1 protein level by Western blot.
      Furthermore, this protein was located by immunohistochemistry in the same organs.
      The transcripts were ubiquitously expressed, but at a higher level in testis and
      liver, while the protein was more abundant in testis and skin. Moreover, the
      ERalpha1 was detected in endothelial, Kupffer, mucous and chloride cells,
      hematopoietic tissues, proximal tubule, epithelia of the skin and intestine, in
      the lamina propria and in the stratum granulosum. This distribution backs the
      idea that, in male rainbow trout, estrogeno-mimetic compounds could be involved
      in different immune mechanisms such as inflammatory response, transport of Ig,
      mucus production, regulation of cellular immunity and development and maturation
      of lymphoid and myeloid cells. 

PMID- 24937419
TI  - Vessel-dependent recruitment of sympathetic axons: looking for innervation in all
      the right places.
AB  - Autonomic sympathetic axons extend along and innervate resistance arteries to
      control vascular tone and participate in blood pressure regulation. In this issue
      of the JCI, Brunet and colleagues reveal that sympathetic innervation of arteries
      is facilitated by secretion of the axon guidance molecule netrin-1 by arterial
      VSMCs. Furthermore, disruption of the signaling cascade induced by netrin-1
      through its receptor DCC resulted in defective arterial innervation and
      sympathetic control of vasoconstriction. This comprehensive study represents a
      major step forward in our understanding of the coordinated wiring of the vascular
      and nervous systems in various tissues. 

PMID- 24937420
TI  - Fatness and fertility: which direction?
AB  - Metabolic status has long been thought to determine reproductive status, with
      abnormal metabolic phenotypes altering reproductive cascades, such as the onset
      of puberty. In this issue of the JCI, Tolson and colleagues provide evidence that
      kisspeptin, a hormone that promotes sexual maturation, regulates metabolism.
      Female mice lacking the kisspeptin receptor (KISS1R) gained more weight than
      control animals, and this weight gain was caused not by increased food
      consumption, but by an overall decrease in energy and metabolism. While this
      study provides a direct link between the kisspeptin pathway and metabolic output,
      more work will need to be done to determine whether alterations in this pathway
      contribute to human obesity. 

PMID- 24937421
TI  - Twisting mice move the dystonia field forward.
AB  - A common form of the hyperkinetic movement disorder dystonia is caused by
      mutations in the gene TOR1A (located within the DYT1 locus), which encodes the
      ATPase torsinA. The underlying neurobiological mechanisms that result in dystonia
      are poorly understood, and progress in the field has been hampered by the absence
      of a dystonia-like phenotype in animal models with genetic modification of Tor1a.
      In this issue of the JCI, Liang et al. establish the first animal model with a
      dystonic motor phenotype and link torsinA hypofunction to the development of
      early neuropathological changes in distinct sensorimotor regions. The findings of
      this study will likely play an important role in elucidating the neural substrate
      for dystonia and should stimulate systematic neuropathological and imaging
      studies in carriers of TOR1A mutations. 

PMID- 24937422
TI  - Loss of P2Y14 results in an arresting response to hematological stress.
AB  - The regenerative capacity of tissues to recover from injury or stress is
      dependent on stem cell competence, yet the underlying mechanisms that govern how
      stem cells detect stress and initiate appropriate responses are poorly
      understood. In this issue of the JCI, Cho and Yusuf et al. demonstrate that the
      purinergic receptor P2Y14 may mediate the hematopoietic stem and progenitor cell
      regenerative response. 

PMID- 24937423
TI  - Cardiac fibroblasts in pressure overload hypertrophy: the enemy within?
AB  - Cardiac fibroblasts have been long recognized as active participants in heart
      disease; however, their exact physiological and pathological roles remain
      elusive, mainly due to the lack of specific markers. In this issue of the JCI,
      Moore-Morris and colleagues used a fibroblast-specific collagen1a1-GFP reporter
      to demonstrate that fibroblast accumulation after aortic banding in murine hearts
      arises almost exclusively from proliferation of resident fibroblasts originating
      from both the epicardium and a previously unrecognized source, the endocardium.
      Further characterization of fibroblast origin and function in different types and
      stages of heart disease could lead to development of improved fibroblast-targeted
      cardiac therapies. 

PMID- 24937424
TI  - Kidney alpha-intercalated cells and lipocalin 2: defending the urinary tract.
AB  - A growing body of evidence indicates that the kidneys contribute substantially to
      immune defense against pathogens in the urinary tract. In this issue, Paragas et
      al. report that alpha-intercalated cells (A-ICs) within the nephron collecting
      duct sense infecting Gram-negative bacteria, resulting in simultaneously
      secretion of the iron chelating protein lipocalin 2 (LCN2) and protons, which
      acidify the urine. A-IC-specific LCN2 and proton secretion markedly reduced the
      ability of infecting uropathogenic E. coli (UPEC) to grow and sustain infection.
      The capacity of A-ICs to sense and actively promote clearance of infecting
      bacteria in the lower urinary tract represents a novel function for these
      specialized kidney cells, which are best known for their role in modulating acid
      base homeostasis. 

PMID- 24937425
TI  - Designer receptors: therapeutic adjuncts to cell replacement therapy in
      Parkinson's disease.
AB  - Cell replacement for restoring neuronal populations in Parkinson's disease has
      been demonstrated as a potential therapeutic strategy over several decades of
      studies; however, a number of issues regarding sources of replacement neurons and
      optimization of therapeutic efficacy in vivo have hampered clinical
      implementation. In this issue of the JCI, Dell'Anno and colleagues evaluated the
      use of induced dopaminergic (iDA) neurons that were generated by direct
      fibroblast reprogramming for transplantation and demonstrated that postmitotic
      iDA neurons stably and functionally integrate into host striatum to produce motor
      improvements in 6-OHDA rats, a Parkinson's disease model. Furthermore, using
      designer receptors exclusively activated by designer drugs (DREADDs) in iDA
      grafts to noninvasively increase dopamine release from grafted neurons, the
      authors were able to remotely control transplanted neurons and enhance
      therapeutic efficacy. This initial proof-of-concept study is the first
      application of DREADD technology to treat neurodegenerative dysfunction, and by
      using DREADDs as an adjunct to iDA cell therapy, it presents a novel strategy to
      overcome some current caveats of cell replacement therapy. 

PMID- 24937426
TI  - Purinergic P2Y14 receptor modulates stress-induced hematopoietic stem/progenitor
      cell senescence.
AB  - Purinergic receptors of the P2Y family are G protein-coupled surface receptors
      that respond to extracellular nucleotides and can mediate responses to local cell
      damage. P2Y-dependent signaling contributes to thrombotic and/or inflammatory
      consequences of tissue injury by altering platelet and endothelial activation and
      immune cell phagocytosis. Here, we have demonstrated that P2Y14 modifies cell
      senescence and cell death in response to tissue stress, thereby enabling
      preservation of hematopoietic stem/progenitor cell function. In mice, P2Y14
      deficiency had no demonstrable effect under homeostatic conditions; however,
      radiation stress, aging, sequential exposure to chemotherapy, and serial bone
      marrow transplantation increased senescence in animals lacking P2Y14. Enhanced
      senescence coincided with increased ROS, elevated p16(INK4a) expression, and
      hypophosphorylated Rb and was inhibited by treatment with a ROS scavenger or
      inhibition of p38/MAPK and JNK. Treatment of WT cells with pertussis toxin
      recapitulated the P2Y14 phenotype, suggesting that P2Y14 mediates antisenescence
      effects through Gi/o protein-dependent pathways. Primitive hematopoietic cells
      lacking P2Y14 were compromised in their ability to restore hematopoiesis in
      irradiated mice. Together, these data indicate that P2Y14 on stem/progenitor
      cells of the hematopoietic system inhibits cell senescence by monitoring and
      responding to the extracellular manifestations of tissue stress and suggest that
      P2Y14-mediated responses prevent the premature decline of regenerative capacity
      after injury.

PMID- 24937427
TI  - Impaired kisspeptin signaling decreases metabolism and promotes glucose
      intolerance and obesity.
AB  - The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin
      releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition
      to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues,
      which suggests that kisspeptin has additional functions beyond reproduction.
      Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin
      signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females
      displayed dramatically higher BW, leptin levels, and adiposity, along with
      strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal
      BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females
      ate less than WT females; however, Kiss1r KO females displayed markedly reduced
      locomotor activity, respiratory rate, and energy expenditure, which were not due
      to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r
      KO females was not solely reflective of absent gonadal estrogen, as chronically
      ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced
      metabolism, and glucose intolerance compared with ovariectomized WT females. Our
      findings demonstrate that in addition to reproduction, kisspeptin signaling
      influences BW, energy expenditure, and glucose homeostasis in a sexually
      dimorphic and partially sex steroid-independent manner; therefore, alterations in
      kisspeptin signaling might contribute, directly or indirectly, to some facets of
      human obesity, diabetes, or metabolic dysfunction. 

PMID- 24937429
TI  - TorsinA hypofunction causes abnormal twisting movements and sensorimotor circuit
      neurodegeneration.
AB  - Lack of a preclinical model of primary dystonia that exhibits dystonic-like
      twisting movements has stymied identification of the cellular and molecular
      underpinnings of the disease. The classical familial form of primary dystonia is
      caused by the DYT1 (DeltaE) mutation in TOR1A, which encodes torsinA, AAA+ ATPase
      resident in the lumen of the endoplasmic reticular/nuclear envelope. Here, we
      found that conditional deletion of Tor1a in the CNS (nestin-Cre Tor1a(flox/-)) or
      isolated CNS expression of DYT1 mutant torsinA (nestin-Cre Tor1a(flox/DeltaE))
      causes striking abnormal twisting movements. These animals developed perinuclear
      accumulation of ubiquitin and the E3 ubiquitin ligase HRD1 in discrete
      sensorimotor regions, followed by neurodegeneration that was substantially milder
      in nestin-Cre Tor1a(flox/DeltaE) compared with nestin-Cre Tor1a(flox/-) animals.
      Similar to the neurodevelopmental onset of DYT1 dystonia in humans, the
      behavioral and histopathological abnormalities emerged and became fixed during
      CNS maturation in the murine models. Our results establish a genetic model of
      primary dystonia that is overtly symptomatic, and link torsinA hypofunction to
      neurodegeneration and abnormal twisting movements. These findings provide a
      cellular and molecular framework for how impaired torsinA function selectively
      disrupts neural circuits and raise the possibility that discrete foci of
      neurodegeneration may contribute to the pathogenesis of DYT1 dystonia.

PMID- 24937428
TI  - alpha-Intercalated cells defend the urinary system from bacterial infection.
AB  - alpha-Intercalated cells (A-ICs) within the collecting duct of the kidney are
      critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as
      both sentinels and effectors in the defense against urinary infections. In a
      murine urinary tract infection model, A-ICs bound uropathogenic E. coli and
      responded by acidifying the urine and secreting the bacteriostatic protein
      lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required
      TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels
      of LCN2. The presence of LCN2 in urine was both necessary and sufficient to
      control the urinary tract infection through iron sequestration, even in the harsh
      condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and
      urinary acidification were reduced, and consequently bacterial clearance was
      limited. Together these results indicate that A-ICs, which are known to regulate
      acid-base metabolism, are also critical for urinary defense against pathogenic
      bacteria. They respond to both cystitis and pyelonephritis by delivering
      bacteriostatic chemical agents to the lower urinary system. 

PMID- 24937430
TI  - Stromal heparan sulfate differentiates neuroblasts to suppress neuroblastoma
      growth.
AB  - Neuroblastoma prognosis is dependent on both the differentiation state and
      stromal content of the tumor. Neuroblastoma tumor stroma is thought to suppress
      neuroblast growth via release of soluble differentiating factors. Here, we
      identified critical growth-limiting components of the differentiating stroma
      secretome and designed a potential therapeutic strategy based on their central
      mechanism of action. We demonstrated that expression of heparan sulfate
      proteoglycans (HSPGs), including TbetaRIII, GPC1, GPC3, SDC3, and SDC4, is low in
      neuroblasts and high in the Schwannian stroma. Evaluation of neuroblastoma
      patient microarray data revealed an association between TGFBR3, GPC1, and SDC3
      expression and improved prognosis. Treatment of neuroblastoma cell lines with
      soluble HSPGs promoted neuroblast differentiation via FGFR1 and ERK
      phosphorylation, leading to upregulation of the transcription factor inhibitor of
      DNA binding 1 (ID1). HSPGs also enhanced FGF2-dependent differentiation, and the
      anticoagulant heparin had a similar effect, leading to decreased neuroblast
      proliferation. Dissection of individual sulfation sites identified 2-O, 3-O
      desulfated heparin (ODSH) as a differentiating agent, and treatment of orthotopic
      xenograft models with ODSH suppressed tumor growth and metastasis without
      anticoagulation. These studies support heparan sulfate signaling intermediates as
      prognostic and therapeutic neuroblastoma biomarkers and demonstrate that tumor
      stroma biology can inform the design of targeted molecular therapeutics. 

PMID- 24937431
TI  - Remote control of induced dopaminergic neurons in parkinsonian rats.
AB  - Direct lineage reprogramming through genetic-based strategies enables the
      conversion of differentiated somatic cells into functional neurons and distinct
      neuronal subtypes. Induced dopaminergic (iDA) neurons can be generated by direct
      conversion of skin fibroblasts; however, their in vivo phenotypic and functional
      properties remain incompletely understood, leaving their impact on Parkinson's
      disease (PD) cell therapy and modeling uncertain. Here, we determined that iDA
      neurons retain a transgene-independent stable phenotype in culture and in animal
      models. Furthermore, transplanted iDA neurons functionally integrated into host
      neuronal tissue, exhibiting electrically excitable membranes, synaptic currents,
      dopamine release, and substantial reduction of motor symptoms in a PD animal
      model. Neuronal cell replacement approaches will benefit from a system that
      allows the activity of transplanted neurons to be controlled remotely and enables
      modulation depending on the physiological needs of the recipient; therefore, we
      adapted a DREADD (designer receptor exclusively activated by designer drug)
      technology for remote and real-time control of grafted iDA neuronal activity in
      living animals. Remote DREADD-dependent iDA neuron activation markedly enhanced
      the beneficial effects in transplanted PD animals. These data suggest that iDA
      neurons have therapeutic potential as a cell replacement approach for PD and
      highlight the applicability of pharmacogenetics for enhancing cellular signaling
      in reprogrammed cell-based approaches. 

PMID- 24937432
TI  - Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis.
AB  - Activation and accumulation of cardiac fibroblasts, which result in excessive
      extracellular matrix deposition and consequent mechanical stiffness, myocyte
      uncoupling, and ischemia, are key contributors to heart failure progression.
      Recently, endothelial-to-mesenchymal transition (EndoMT) and the recruitment of
      circulating hematopoietic progenitors to the heart have been reported to generate
      substantial numbers of cardiac fibroblasts in response to pressure overload
      induced injury; therefore, these processes are widely considered to be promising
      therapeutic targets. Here, using multiple independent murine Cre lines and a
      collagen1a1-GFP fusion reporter, which specifically labels fibroblasts, we found
      that following pressure overload, fibroblasts were not derived from hematopoietic
      cells, EndoMT, or epicardial epithelial-to-mesenchymal transition. Instead,
      pressure overload promoted comparable proliferation and activation of two
      resident fibroblast lineages, including a previously described epicardial
      population and a population of endothelial origin. Together, these data present a
      paradigm for the origins of cardiac fibroblasts during development and in
      fibrosis. Furthermore, these data indicate that therapeutic strategies for
      reducing pathogenic cardiac fibroblasts should shift from targeting presumptive
      EndoMT or infiltrating hematopoietically derived fibroblasts, toward common
      pathways upregulated in two endogenous fibroblast populations. 

PMID- 24937435
TI  - Effect of binders on airborne microorganism inactivation using TiO2
      photocatalytic fluorescent lamps.
AB  - 5% Degussa P25 TiO2 was spray-coated onto black-light and white-light fluorescent
      lamps, using five different binders, namely DURAMAX B-1000, DURAMAX D-3005,
      silane-69, and two polyethylene glycols with molecular weight 1000 (PEG-1000) and
      700 (PEG-700). The coated lamps were tested with Staphylococcus epidermidis,
      Escherichia coli, spores of Bacillus subtilis and spores of Aspergillus niger. It
      was found that 0.5% B-1000 and 1% PEG-1000 gave the highest inactivation rates:
      93-96% from coated black-light lamps and 85-88% from coated white-light lamps for
      bacteria. In the case of spores, 70-72% and 55-57% inactivation rates were
      recorded from coated black-light and coated white-light lamps, respectively. The
      effects of UVA irradiance and face velocity were also examined. Significant
      improvement was observed from coated white-light lamps when the UVA irradiance
      increased. High face velocity adversely affected microorganism inactivation. 

PMID- 24937433
TI  - Netrin-1 controls sympathetic arterial innervation.
AB  - Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby
      regulating vascular tone and controlling blood supply to organs. Despite the
      fundamental importance of blood flow control, how sympathetic arterial
      innervation develops remains largely unknown. Here, we identified the axon
      guidance cue netrin-1 as an essential factor required for development of arterial
      innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs)
      at the onset of innervation, and arterial innervation required the interaction of
      netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic
      growth cones. Function-blocking approaches, including cell type-specific deletion
      of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe
      and selective reduction of sympathetic innervation and to defective
      vasoconstriction in resistance arteries. These findings indicate that netrin-1
      and DCC are critical for the control of arterial innervation and blood flow
      regulation in peripheral organs. 

PMID- 24937436
TI  - Yellowing and bleaching of grey hair caused by photo and thermal degradation.
AB  - Yellowing is an undesirable phenomenon that is common in people with white and
      grey hair. Because white hair has no melanin, the pigment responsible for hair
      colour, the effects of photodegradation are more visible in this type of hair.
      The origin of yellowing and its relation to photodegradation processes are not
      properly established, and many questions remain open in this field. In this work,
      the photodegradation of grey hair was investigated as a function of the
      wavelength of incident radiation, and its ultrastructure was determined, always
      comparing the results obtained for the white and black fibres present in grey
      hair with the results of white wool. The results presented herein indicate that
      the photobehaviour of grey hair irradiated with a mercury lamp or with solar
      radiation is dependent on the wavelength range of the incident radiation and on
      the initial shade of yellow in the sample. Two types of grey hair were used: (1)
      blended grey hair (more yellow) and (2) grey hair from a single-donor (less
      yellow). After exposure to a full-spectrum mercury lamp for 200 h, the blended
      white hair turned less yellow (the yellow-blue difference, Db(*) becomes
      negative, Db(*)=-6), whereas the white hair from the single-donor turned slightly
      yellower (Db(*)=2). In contrast, VIS+IR irradiation resulted in bleaching in both
      types of hair, whereas a thermal treatment (at 81  degrees C) caused yellowing of
      both types of hair, resulting in a Db(*)=3 for blended white hair and Db(*)=9 for
      single-donor hair. The identity of the yellow chromophores was investigated by UV
      Vis spectroscopy. The results obtained with this technique were contradictory,
      however, and it was not possible to obtain a simple correlation between the
      sample shade of yellow and the absorption spectra. In addition, the results are
      discussed in terms of the morphology differences between the pigmented and non
      pigmented parts of grey hair, the yellowing and bleaching effects of grey hair,
      and the occurrence of dark-follow reactions.

PMID- 24937434
TI  - Epigenetic regulation of smooth muscle cell plasticity.
AB  - Smooth muscle cells (SMC) are the major cell type in blood vessels. Their
      principal function in the body is to regulate blood flow and pressure through
      vessel wall contraction and relaxation. Unlike many other mature cell types in
      the adult body, SMC do not terminally differentiate but retain a remarkable
      plasticity. They have the unique ability to toggle between a differentiated and
      quiescent "contractile" state and a highly proliferative and migratory
      "synthetic" phenotype in response to environmental stresses. While there have
      been major advances in our understanding of SMC plasticity through the
      identification of growth factors and signals that can influence the SMC
      phenotype, how these regulate SMC plasticity remains unknown. To date, several
      key transcription factors and regulatory cis elements have been identified that
      play a role in modulating SMC state. The frontier in understanding the molecular
      mechanisms underlying SMC plasticity has now advanced to the level of
      epigenetics. This review will summarize the epigenetic regulation of SMC,
      highlighting the role of histone modification, DNA methylation, and our most
      recent identification of a DNA demethylation pathway in SMC that is pivotal in
      the regulation of the SMC phenotypic state. Many disorders are associated with
      smooth muscle dysfunction, including atherosclerosis, the major underlying cause
      of stroke and coronary heart disease, as well as transplant vasculopathy,
      aneurysm, asthma, hypertension, and cancer. An increased understanding of the
      major regulators of SMC plasticity will lead to the identification of novel
      target molecules that may, in turn, lead to novel drug discoveries for the
      treatment of these diseases. This article is part of a Special Issue entitled:
      Stress as a fundamental theme in cell plasticity. 

PMID- 24937437
TI  - Orexin A enhances locomotor activity and induces anxiogenic-like action in the
      goldfish, Carassius auratus.
AB  - Orexin acts as an orexigenic factor for the regulation of appetite and
      rhythmicity in rodents. In goldfish, intracerebroventricular (ICV) administration
      of orexin A has been shown to affect not only food intake, but also locomotor
      activity. However, as there is still no information regarding the effect of
      orexin A on emotional behavior in goldfish, we investigated the effect of orexin
      A on psychomotor activity in this species. Intracerebroventricular administration
      of synthetic orexin A at 2 and 4pmol/g body weight (BW) enhanced locomotor
      activity, and this enhancement by orexin A at 4pmol/g BW was attenuated by
      treatment with the orexin receptor 1 antagonist, SB334867, at 10pmol/g BW. Since
      intact goldfish prefer a black to a white background area, or the lower to the
      upper area of a tank, we used two types of preference tests (black/white and
      upper/lower tests) for measuring anxiety-like behavior in goldfish.
      Intracerebroventricular administration of orexin A at 4pmol/g BW shortened the
      time spent in the white background area, and increased the time taken to move
      from the lower to the upper area. This action of orexin A mimicked that of the
      central-type benzodiazepine receptor inverse agonist, FG-7142 (an anxiogenic
      agent), at 4pmol/g BW. The anxiogenic-like effect of orexin A was abolished by
      treatment with SB334867 at 10pmol/g BW. These results indicate that orexin A
      potently affects psychomotor activity in goldfish. 

PMID- 24937439
TI  - Nandrolone-induced aggressive behavior is associated with alterations in
      extracellular glutamate homeostasis in mice.
AB  - Nandrolone decanoate (ND), an anabolic androgenic steroid (AAS), induces an
      aggressive phenotype by mechanisms involving glutamate-induced N-methyl-d
      aspartate receptor (NMDAr) hyperexcitability. The astrocytic glutamate
      transporters remove excessive glutamate surrounding the synapse. However, the
      impact of supraphysiological doses of ND on glutamate transporters activity
      remains elusive. We investigated whether ND-induced aggressive behavior is
      interconnected with GLT-1 activity, glutamate levels and abnormal NMDAr
      responses. Two-month-old untreated male mice (CF1, n=20) were tested for baseline
      aggressive behavior in the resident-intruder test. Another group of mice (n=188)
      was injected with ND (15mg/kg) or vehicle for 4, 11 and 19days (short-, mid- and
      long-term endpoints, respectively) and was evaluated in the resident-intruder
      test. Each endpoint was assessed for GLT-1 expression and glutamate uptake
      activity in the frontoparietal cortex and hippocampal tissues. Only the long-term
      ND endpoint significantly decreased the latency to first attack and increased the
      number of attacks, which was associated with decreased GLT-1 expression and
      glutamate uptake activity in both brain areas. These alterations may affect
      extracellular glutamate levels and receptor excitability. Resident males were
      assessed for hippocampal glutamate levels via microdialysis both prior to, and
      following, the introduction of intruders. Long-term ND mice displayed significant
      increases in the microdialysate glutamate levels only after exposure to
      intruders. A single intraperitoneal dose of the NMDAr antagonists, memantine or
      MK-801, shortly before the intruder test decreased aggressive behavior. In
      summary, long-term ND-induced aggressive behavior is associated with decreased
      extracellular glutamate clearance and NMDAr hyperexcitability, emphasizing the
      role of this receptor in mediating aggression mechanisms. 

PMID- 24937438
TI  - Assessment of the effects of sex and sex hormones on spatial cognition in adult
      rats using the Barnes maze.
AB  - Although sex differences and hormone effects on spatial cognition are observed in
      humans and animals, consensus has not been reached regarding exact impact on
      spatial working or reference memory. Recent studies in rats suggest that stress
      and/or reward, which are often different in tasks used to assess spatial
      cognition, can contribute to the inconsistencies in the literature. To minimize
      the impact of these sex- and sex hormone-sensitive factors, we used the Barnes
      maze to compare spatial working memory, spatial reference memory and spatial
      learning strategy in adult male, female, gonadectomized (GDX) male, and GDX male
      rats supplemented with 17beta-estradiol (E) or testosterone propionate (TP). Rats
      received four acquisition trials, four trials 24h later, and a single retention
      trial one week after. Males and females acquired the task during the first four
      trials and retained the task thereafter. In contrast, GDX rats took longer to
      acquire the task and showed retention deficits at 1week. All deficits were
      attenuated similarly by TP and E. Assessment of search patterns also showed that
      strategies in the males transitioned from random to spatially focused and
      eventually direct approaches to the goal. However, this transition was faster in
      control and GDX-TP than in GDX and GDX-E rats. In contrast, the females almost
      invariantly followed the maze edge in thigmotactic, serial searches. Thus, while
      Barnes maze reveals activational, in part estrogenic effects on spatial cognition
      in males, its amenability to animals' use of multiple strategies may limit its
      ability to resolve mnemonic differences across sex. 

PMID- 24937440
TI  - Long-term safety and effectiveness of tanezumab as treatment for chronic low back
      pain.
AB  - A noncontrolled, randomized, multicenter study (NCT00924664) evaluated long-term
      safety and effectiveness of tanezumab in patients with chronic low back pain
      following a randomized placebo- and active-controlled parent study that evaluated
      analgesic efficacy. Patients were randomized to tanezumab 10mg (n=321) or 20mg
      (n=527) administered at 8-week intervals via 3 intravenous injections followed by
      4 subcutaneous injections. Effectiveness analyses included change from parent
      study baseline in Brief Pain Inventory Short Form, Roland Morris Disability
      Questionnaire, and Patient's Global Assessment of low back pain. Safety
      assessments included adverse event documentation, physical/neurological
      examinations, and laboratory tests. Mean treatment duration during the extension
      study was 194 and 202 days with tanezumab 10 and 20mg, respectively. Both
      tanezumab doses provided similar and sustained improvements in all effectiveness
      outcomes. The most frequently reported adverse events were arthralgia,
      paresthesia, and hypoesthesia. Adverse events initially described as
      osteonecrosis were reported in 6 patients (tanezumab 10mg, n=2; tanezumab 20mg,
      n=4); 9 additional patients (tanezumab 10mg, n=7; tanezumab 20mg, n=2) underwent
      total joint replacement (TJR). A blinded, independent adjudication committee
      reviewed all 6 patients with reported osteonecrosis and 4 of the 9 patients
      undergoing TJR. Adjudication outcomes were osteonecrosis (n=0), worsening
      osteoarthritis (n=5; 1 rapidly progressive), and another diagnosis or
      indeterminate (n=5). Tanezumab 10mg had better tolerability than tanezumab 20mg,
      and may represent an effective long-term treatment for chronic low back pain.

PMID- 24937441
TI  - Species composition, abundance, and seasonal dynamics of stink bugs (Hemiptera:
      Pentatomidae) in Minnesota soybean fields.
AB  - Stink bugs (Hemiptera: Pentatomidae) have historically not been pests of soybean
      in Minnesota. In response to the invasion of Halyomorpha halys (Stal) and reports
      of increasing abundance of species native to North America, a state-wide survey
      of soybean was conducted over 3 yr in Minnesota to determine species composition,
      abundance, and seasonal dynamics of Pentatomidae associated with soybean.
      Fourteen species of Pentatomidae (12 herbivorous and two predatory) were
      collected from soybean. H. halys was not detected in this survey. Among the
      herbivorous species found, adults of Euschistus variolarius (Palisot de Beauvois)
      had the greatest relative abundance (60.51%) and frequency of detection (18.44%),
      followed by Euschistus servus euschistoides (Say) (19.37 and 3.04%, respectively)
      and Chinavia hilaris (Say) (5.50 and 1.69%, respectively). Abundance of
      herbivorous nymphs and adults exceeded an economic threshold (20 nymphs and
      adults per 100 sweeps) in 0.82% of fields in 2012 but not in 2011 or 2013. The
      frequency of detection of herbivorous species and ratio of nymphs to adults
      increased with increasing reproductive growth stage of soybean. In two of three
      years, herbivorous adults were more abundant in the edge compared with interior
      of fields. Two predatory Pentatomidae, Podisus maculiventris (Say) and Podisus
      placidus Uhler, comprised 5.95 and 1.62% of the pentatomid adults. Though the
      species composition of Pentatomidae in Minnesota soybean differs from that in
      eastern and southern states, the spatial (i.e., greater abundance near field
      edge) and seasonal dynamics (i.e., increasing abundance and reproduction with
      increasing reproductive maturity of soybean) in soybean appear similar. 

PMID- 24937442
TI  - Lanthanide-organic coordination frameworks showing new 5-connected network
      topology and 3D ordered array of single-molecular magnet behavior in the Dy case.
AB  - Five isostructural lanthanide-organic coordination frameworks with a unique 3-D 5
      connected (4(7).6(3))(4(3).6(5).8(2)) network, namely, [Ln(phen)(L)]n (Ln = Dy
      for 1, Gd for 2, Ho for 3, Er for 4, and Tb for 5), have been prepared based on
      bridging 5-hydroxyisophthalic acid (H3L) and chelating 1,10-phenanthroline (phen)
      coligand. Significantly, the Dy(III) complex 1 is an organized array of single
      molecular magnets (SMMs), with frequency-dependent out-of-phase ac susceptibility
      signals and magnetization hysteresis at 4 K. Further analysis of the magnetic
      results can reveal that the SMM behavior of 1 should arise from the smaller
      ferromagnetic interaction between the Dy(III) ions. Complex 1 was also
      characterized by X-ray absorption spectra, which give the clear X-ray magnetic
      circular dichroism signal. 

PMID- 24937443
TI  - Risk factors for malformations and impact on reproductive performance and
      mortality rates of Schmallenberg virus in sheep flocks in the Netherlands.
AB  - In Northwestern Europe, an epizootic outbreak of congenital malformations in
      newborn lambs due to infection with Schmallenberg virus (SBV) started at the end
      of 2011. The objectives of this study were to describe clinical symptoms of SBV
      infection, the effect of infection on mortality rates, and reproductive
      performance in sheep, as well as to identify and quantify flock level risk
      factors for SBV infections resulting in malformations in newborn lambs. A case
      control study design was used, with 93 case flocks that had notified malformed
      lambs and 84 control flocks with no such lambs. Overall animal seroprevalence in
      case flocks was estimated at 82.0% (95% CI: 74.3-87.8), and was not significantly
      different from the prevalence in control flocks being 76.4% (95% CI: 67.2-83.6).
      The percentages of stillborn lambs or lambs that died before weaning, repeat
      breeders, and lambs with abnormal suckling behaviour were significantly higher in
      case flocks compared to control flocks. However, effect of SBV infection on
      mortality rates and reproductive performance seemed to be limited. Multivariable
      analysis showed that sheep flocks with an early start of the mating season, i.e.
      before August 2011 (OR = 33.1; 95% CI: 10.0-109.8) and in August 2011 (OR = 8.2;
      95% CI: 2.7-24.6) had increased odds of malformations in newborn lambs caused by
      SBV compared to sheep flocks with a start of the mating season in October 2011.
      Other flock-level risk factors for malformations in newborn lambs were purchase
      of silage (OR 5.0; 95% CI: 1.7-15.0) and flocks with one or more dogs (OR = 3.3;
      95% CI: 1.3-8.3). Delaying mating until October could be a potential preventive
      measure for naive animals to reduce SBV induced losses. As duration of immunity
      after infection with SBV is expected to last for several years, future SBV
      induced congenital malformations are mainly expected in offspring of early mated
      seronegative animals. 

PMID- 24937444
TI  - DNA methylation-associated colonic mucosal immune and defense responses in
      treatment-naive pediatric ulcerative colitis.
AB  - Inflammatory bowel diseases (IBD) are emerging globally, indicating that
      environmental factors may be important in their pathogenesis. Colonic mucosal
      epigenetic changes, such as DNA methylation, can occur in response to the
      environment and have been implicated in IBD pathology. However, mucosal DNA
      methylation has not been examined in treatment-naive patients. We studied DNA
      methylation in untreated, left sided colonic biopsy specimens using the Infinium
      HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15
      untreated Crohn's disease (CD) patients, and 9 untreated ulcerative colitis (UC)
      patients from two cohorts. Samples obtained at the time of clinical remission
      from two of the treatment-naive UC patients were also included into the analysis.
      UC-specific gene expression was interrogated in a subset of adjacent samples (5 C
      and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays.
      Only treatment-naive UC separated from control. One-hundred-and-twenty genes with
      significant expression change in UC (> 2-fold, P<0.05) were associated with
      differentially methylated regions (DMRs). Epigenetically associated gene
      expression changes (including gene expression changes in the IFITM1, ITGB2,
      S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and
      defense responses. These findings underscore the relationship between epigenetic
      changes and inflammation in pediatric treatment-naive UC and may have potential
      etiologic, diagnostic, and therapeutic relevance for IBD. 

PMID- 24937446
TI  - Promiscuity of Exiguobacterium sp. AT1b o-succinylbenzoate synthase illustrates
      evolutionary transitions in the OSBS family.
AB  - Catalytic promiscuity, which is the ability to catalyze more than one reaction in
      the same active site, is thought to facilitate the evolution of new protein
      functions. Although many enzymes are catalytically promiscuous, there is little
      direct evidence to show how promiscuous activities evolved into biological
      functions. We are seeking evidence for this model by studying the o
      succinylbenzoate synthase (OSBS) family. Most enzymes within this family only
      catalyze OSBS, which is a step in menaquinone synthesis. However, several
      characterized enzymes in one branch of the family (called the NSAR/OSBS
      subfamily) efficiently catalyze both OSBS and N-succinylamino acid racemization
      (NSAR). Based on genome context, NSAR appears to be the only biological function
      of some characterized NSAR/OSBS enzymes, while both activities are biologically
      relevant in others. The promiscuity model predicts that these enzymes evolved
      from an ancestral OSBS which promiscuously catalyzed NSAR as a side reaction that
      was not biologically relevant. If so, the model predicts that some extant OSBS
      enzymes would have low levels of promiscuous NSAR activity. This manuscript
      describes such an enzyme from Exiguobacterium sp. AT1b (ExiOSBS). We show that
      ExiOSBS efficiently catalyzes OSBS (kcat/KM=2.6*10(6) M(-1) s(-1)), but its
      efficiency for the NSAR reaction is only 41 M(-1) s(-1). Moreover, genome context
      indicates that OSBS is the only biologically relevant activity. ExiOSBS diverged
      from the NSAR/OSBS subfamily before NSAR emerged as a biologically relevant
      activity. These results provide evidence that NSAR activity originated as a
      promiscuous activity in an ancestor of the NSAR/OSBS subfamily.

PMID- 24937445
TI  - LMO4 is required to maintain hypothalamic insulin signaling.
AB  - Insulin action at the hypothalamus controls glucose homeostasis by suppressing
      hepatic glucose production and promoting glucose uptake by muscle. However, the
      mechanisms that control central insulin signaling have not been fully elucidated.
      Previously, we showed that LMO4 is highly expressed in hypothalamic nuclei that
      regulate glucose homeostasis. Here, we determined how loss of LMO4 in the
      hypothalamus would affect central insulin signaling and glucose homeostasis. In
      transgenic mice that have LMO4 in ablated in glutamatergic neurons, we found that
      insulin signaling is impaired in the hypothalamus as well as in peripheral
      tissues (liver and skeletal muscle). Impaired glucose homeostasis was associated
      with a markedly elevation in hypothalamic protein tyrosine phosphatase 1B (PTP1B)
      activity. PTP1B is a key phosphatase that terminates insulin signaling by
      dephosphorylating its receptor and downstream signaling molecules. Importantly,
      we found that administration of a selective PTP1B inhibitor Trodusquemine to the
      hypothalamus restored central insulin signaling and improved the response of
      peripheral tissues to insulin in these LMO4-deficient mice. Thus, our study
      reveals an essential requirement for LMO4 to modulate central insulin signaling. 

PMID- 24937447
TI  - Structural analysis of the yeast exosome Rrp6p-Rrp47p complex by small-angle X
      ray scattering.
AB  - The RNase D-type 3'-5' exonuclease Rrp6p from Saccharomyces cerevisiae is a
      nuclear-specific cofactor of the RNA exosome and associates in vivo with Rrp47p
      (Lrp1p). Here, we show using biochemistry and small-angle X-ray scattering (SAXS)
      that Rrp6p and Rrp47p associate into a stable, heterodimeric complex with an
      elongated shape consistent with binding of Rrp47p to the nuclease domain and
      opposite of the HRDC domain of Rrp6p. Rrp47p reduces the exonucleolytic activity
      of Rrp6p on both single-stranded and structured RNA substrates without
      significantly altering the affinity towards RNA or the ability of Rrp6p to
      degrade RNA secondary structure. 

PMID- 24937448
TI  - Anti-proliferative and pro-apoptotic activity of whole extract and isolated
      indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco
      suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells.
AB  - Phytochemicals may exert chemo-preventive effects on cells of the gastro
      intestinal tract by modulating epigenome-regulated gene expression. The effect of
      the aqueous extract from the edible fruit of Opuntia ficus-indica (OFI extract),
      and of its betalain pigment indicaxanthin (Ind), on proliferation of human colon
      cancer Caco-2 cells has been investigated. Whole extract and Ind caused a dose
      dependent apoptosis of proliferating cells at nutritionally relevant amounts,
      with IC50 400+/-25 mg fresh pulp equivalents/mL, and 115+/-15 MUM (n=9),
      respectively, without toxicity for post-confluent differentiated cells. Ind
      accounted for ~80% of the effect of the whole extract. Ind did not cause
      oxidative stress in proliferating Caco-2 cells. Epigenomic activity of Ind was
      evident as de-methylation of the tumor suppressor p16(INK4a) gene promoter,
      reactivation of the silenced mRNA expression and accumulation of p16(INK4a), a
      major controller of cell cycle. As a consequence, decrease of hyper
      phosphorylated, in favor of the hypo-phosphorylated retinoblastoma was observed,
      with unaltered level of the cycline-dependent kinase CDK4. Cell cycle showed
      arrest in the G2/M-phase. Dietary cactus pear fruit and Ind may have chemo
      preventive potential in intestinal cells.

PMID- 24937449
TI  - Pick1 modulates ephrinB1-induced junctional disassembly through an association
      with ephrinB1.
AB  - Members of the Eph family have been implicated in the formation of cell-cell
      boundaries, cell movement, and positioning during development in the context of
      cancer progression. De-regulation of this signaling system is linked to the
      promotion of more aggressive and metastatic tumor phenotypes in a large variety
      of human cancers, including breast, lung, and prostate cancer, melanoma, and
      leukemia. Thus, it is interesting to consider the case of cancer progression
      where de-regulation of the Eph/ephrin signaling system results in invasion and
      metastasis. Here, we present evidence that Pick1, one of the essential components
      of the adherens junction, recovers ephrinB1-induced cell-cell de-adhesion. Loss
      of Pick1 leads to dissociation of epithelial cells via disruption of the adherens
      junction, a phenotype similar to ephrinB1 overexpression. In addition,
      overexpressed ephrinB1-induced disruption of the adherens junction is rescued via
      binding to Pick1. These data indicate that Pick1 is involved in regulating the
      cell-cell junction in epithelial cells, and this may influence therapeutic
      strategy decisions with regards to cell adhesion molecules in metastatic disease.

PMID- 24937450
TI  - Protective effects of Sapindus mukorossi Gaertn against fatty liver disease
      induced by high fat diet in rats.
AB  - OBJECTIVES: Study the effects of alcohol extract of Sapindus mukorossi Gaertn
      (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal
      endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with
      non-alcoholic fatty liver disease (NAFLD). METHODS: Divide SD rats into control
      group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group
      with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05
      g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the
      model of hepatic adipose, conduct intragastric administration and provide the
      rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample
      and measure aminotransferase and different indexes of blood fat; take hepatic
      tissue for pathological section, and observe the hepatic morphological patterns
      under light microscope; obtain and fix the hepatic tissue after injecting
      perfusate into the body, and observe the changes of fenestrated LSEC under
      scanning electron microscope; observe the ultrastructure of liver cells under
      transmission electron microscope. RESULTS: High-dosage alcohol extracts of
      S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, gamma-GT, and ALP
      level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In
      addition, through the observation from light microscope and electron microscopes,
      the morphology of the hepatic tissue and liver cells as well as the recovery of
      the fenestrated LSEC in the treatment group has become normal. CONCLUSIONS:
      Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and
      improve the pathological changes of the hepatic tissues in NAFLD-rat model, which
      demonstrates the effects of down-regulating fat level and protecting liver.

PMID- 24937451
TI  - The small RNA RyhB homologs from Salmonella typhimurium participate in the
      response to S-nitrosoglutathione-induced stress.
AB  - Typically, the expression of sRNAs is activated in response to environmental
      stimuli in order to regulate gene expression through post-transcriptional
      mechanisms. In the present work we show that the Salmonellatyphimurium paralogous
      sRNAs RyhB-1 and RyhB-2 are induced in response to the nitrosating agent S
      nitrosoglutathione (GSNO). Inactivation of these sRNAs decreased S. typhimurium
      resistance to GSNO and increased the levels of nitrosylated proteins. These
      results prompted us to evaluate a possible role of these sRNAs in nitrosative
      stress resistance. RNA profiling was used as a screen to identify novel RyhB-1
      and RyhB-2 regulated targets. A subset of genes was filtered based on their
      potential role in the response to nitrosative stress and their expression was
      analyzed by quantitative RT-PCR in wild type, single and double mutant strains
      (DeltaryhB1, DeltaryhB2 and DeltaryhB1 DeltaryhB2) treated with GSNO. In response
      to GSNO RyhB-1 and RyhB-2 negatively regulate the expression of the genes cyoABC
      (cytochrome bo oxidase), cydB (cytochrome bd oxidase), cybC (cytochrome b-562),
      and positively regulate the nirBCD operon (nitrite reductase system). Together,
      these results suggest that RyhB-1 and RyhB-2 finely tune the expression of genes
      coding for cytochrome oxidases and the nitrate reductase system, allowing the
      cell to cope with GSNO-induced stress. 

PMID- 24937452
TI  - Histone H4 Lys 20 methyltransferase SET8 promotes androgen receptor-mediated
      transcription activation in prostate cancer.
AB  - Histone methylation status in different lysine residues has an important role in
      transcription regulation. The effect of H4K20 monomethylation (H4K20me1) on
      androgen receptor (AR)-mediated gene transcription remains unclear. Here we show
      that AR agonist stimulates the enrichment of H4K20me1 and SET8 at the promoter of
      AR target gene PSA in an AR dependent manner. Furthermore, SET8 is crucial for
      the transcription activation of PSA. Co-immunoprecipitation analyses demonstrate
      that SET8 interacts with AR. Therefore, we conclude that SET8 is involved in AR
      mediated transcription activation, possibly through its interaction with AR and
      H4K20me1 modification. 

PMID- 24937453
TI  - Targeted next-generation sequencing at copy-number breakpoints for personalized
      analysis of rearranged ends in solid tumors.
AB  - BACKGROUND: The concept of the utilization of rearranged ends for development of
      personalized biomarkers has attracted much attention owing to its clinical
      applicability. Although targeted next-generation sequencing (NGS) for recurrent
      rearrangements has been successful in hematologic malignancies, its application
      to solid tumors is problematic due to the paucity of recurrent translocations.
      However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can
      be utilized for identification of rearranged ends. METHOD: As a proof of concept,
      we performed targeted next-generation sequencing at copy-number breakpoints (TNGS
      CNB) in nine colon cancer cases including seven primary cancers and two cell
      lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive
      single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region
      refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements
      out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)
      amplifiable rearrangements were obtained in six cases (66.7%). And significantly,
      TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable
      rearrangements at candidate sites (19/23), just from filtering of aligned
      sequences, requires little effort for validation. CONCLUSION: Our results
      indicate that TNGS-CNB, with its utility for identification of rearrangements in
      solid tumors, can be successfully applied in the clinical laboratory for cancer
      relapse and therapy-response monitoring.

PMID- 24937454
TI  - Pancreatic cancer stroma: friend or foe?
AB  - Pancreatic cancer desmoplasia is thought to confer biological aggressiveness. In
      this issue of Cancer Cell, Ozdemir and colleagues and Rhim and colleagues
      demonstrate that targeting the stroma results in undifferentiated, aggressive
      pancreatic cancer that responds to checkpoint blockade or antiangiogenic therapy,
      uncovering a protective role by stroma in this cancer. 

PMID- 24937455
TI  - MDS is a stem cell disorder after all.
AB  - Myelodysplastic syndrome (MDS) has long been presumed to be a stem cell disorder,
      but rigorous formal proof has been lacking. In this issue of Cancer Cell, Woll
      and colleagues demonstrate that driver mutations occurring in MDS definitively
      occur in cells with a stem cell phenotype. 

PMID- 24937457
TI  - Gremlins sabotage the mechanisms of cancer stem cell differentiation.
AB  - BMP is highly expressed in glioblastoma and promotes differentiation of cancer
      stem cells (CSCs). Recently, Yan and colleagues found the explanation to this
      apparent paradox by showing that the antagonist of BMP, Gremlin1, is secreted by
      CSCs to protect them against the BMP-induced differentiation. 

PMID- 24937456
TI  - GNAQ/11 mutations in uveal melanoma: is YAP the key to targeted therapy?
AB  - GNAQ and GNA11 are frequently mutated in uveal melanoma, but they remain
      difficult therapeutic targets. In this issue of Cancer Cell, Feng and colleagues
      and Yu and colleagues demonstrate that the oncogenic activity of mutant GNAQ/11
      is mediated at least in part through YAP, potentially uncovering a new
      therapeutic strategy. 

PMID- 24937459
TI  - Leukemia propagating cells rebuild an evolving niche in response to therapy.
AB  - Residence of cancer-propagating cells (CPCs) within preferential
      microenvironmental niches has a major part in evading therapy. However, the
      nature of niches involved and the mechanisms protecting CPCs remain largely
      unknown. We addressed these issues in mouse transplantation models of acute
      lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially
      damaged adjacent microenvironment in the bone marrow (BM), after chemotherapy
      small foci of CPCs were retained, surrounded by sheaths of supporting cells that
      comprise a protective niche. We investigated patients' BM biopsies and found
      evidence of a similar process in patients receiving induction therapy. The
      efficacy of chemotherapy was enhanced by interfering with the niche formation or
      function. We therefore identified a therapy-induced niche that protects CPCs. 

PMID- 24937461
TI  - Abatement cost of GHG emissions for wood-based electricity and ethanol at
      production and consumption levels.
AB  - Woody feedstocks will play a critical role in meeting the demand for biomass
      based energy products in the US. We developed an integrated model using
      comparable system boundaries and common set of assumptions to ascertain unit cost
      and greenhouse gas (GHG) intensity of electricity and ethanol derived from slash
      pine (Pinus elliottii) at the production and consumption levels by considering
      existing automobile technologies. We also calculated abatement cost of greenhouse
      gas (GHG) emissions with respect to comparable energy products derived from
      fossil fuels. The production cost of electricity derived using wood chips was at
      least cheaper by 1 c MJ-1 over electricity derived from wood pellets. The
      production cost of ethanol without any income from cogenerated electricity was
      costlier by about 0.7 c MJ-1 than ethanol with income from cogenerated
      electricity. The production cost of electricity derived from wood chips was
      cheaper by at least 0.7 c MJ-1 than the energy equivalent cost of ethanol
      produced in presence of cogenerated electricity. The cost of using ethanol as a
      fuel in a flex-fuel vehicle was at least higher by 6 c km-1 than a comparable
      electric vehicle. The GHG intensity of per km distance traveled in a flex-fuel
      vehicle was greater or lower than an electric vehicle running on electricity
      derived from wood chips depending on presence and absence of GHG credits related
      with co-generated electricity. A carbon tax of at least $7 Mg CO2e-1 and $30 Mg
      CO2e-1 is needed to promote wood-based electricity and ethanol production in the
      US, respectively. The range of abatement cost of GHG emissions is significantly
      dependent on the harvest age and selected baseline especially for electricity
      generation. 

PMID- 24937458
TI  - JARID1B is a luminal lineage-driving oncogene in breast cancer.
AB  - Recurrent mutations in histone-modifying enzymes imply key roles in
      tumorigenesis, yet their functional relevance is largely unknown. Here, we show
      that JARID1B, encoding a histone H3 lysine 4 (H3K4) demethylase, is frequently
      amplified and overexpressed in luminal breast tumors and a somatic mutation in a
      basal-like breast cancer results in the gain of unique chromatin binding and
      luminal expression and splicing patterns. Downregulation of JARID1B in luminal
      cells induces basal genes expression and growth arrest, which is rescued by
      TGFbeta pathway inhibitors. Integrated JARID1B chromatin binding, H3K4
      methylation, and expression profiles suggest a key function for JARID1B in
      luminal cell-specific expression programs. High luminal JARID1B activity is
      associated with poor outcome in patients with hormone receptor-positive breast
      tumors. 

PMID- 24937465
TI  - Type 2 diabetes is not associated with an altered plaque phenotype among patients
      undergoing carotid revascularization. A histological analysis of 1455 carotid
      plaques.
AB  - AIMS: Diabetes accelerates progression of atherosclerotic disease, but data on
      associations between diabetes and advanced atherosclerotic plaque composition are
      scarce. METHODS AND RESULTS: We used one of the largest biobanks, the Athero
      Express study (n=1455) at carotid endarterectomy (CEA). All plaques were
      subjected to histological analysis to assess lipid core size, collagen,
      macrophages, smooth muscle cells, micro-vessel density and calcifications. In
      addition, within a subset of patients cytokines and chemokines were assessed. The
      295 patients (20%) with type-2 diabetes showed a higher proportion of previous
      cardiovascular interventions and more stringent treatment for hypertension and
      hypercholesterolaemia compared with patients without type-2 diabetes.
      Surprisingly, no associations between diabetes and histological plaque
      characteristics were observed. In addition, no differences were observed in the
      expression of inflammatory chemokines, cytokines or advanced glycation end
      products in plaques of diabetic and non-diabetic patients. CONCLUSION: In
      patients suffering from significant carotid artery disease, diabetes does not
      appear to be associated with specific atherosclerotic plaque characteristics.

PMID- 24937466
TI  - Clinical characteristics of high plasma adiponectin and high plasma leptin as
      risk factors for arterial stiffness and related end-organ damage.
AB  - OBJECTIVE: The relationship between plasma levels of adiponectin and
      cardiovascular events is inconclusive. We evaluated the clinical characteristics
      of people with high plasma adiponectin and high plasma leptin levels. METHODS:
      Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc
      were divided into four groups by combining the bipartiles of plasma adiponectin
      and leptin levels in men and women separately: AL, high adiponectin and high
      leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin;
      aL, low adiponectin and high leptin. Body composition, including visceral fat
      area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave
      velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion,
      were determined. RESULTS: Twenty percent of the studied population fell within
      the AL group. This group had a significantly higher visceral fat area than the Al
      group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain
      white matter lesions, and albuminuria findings in the AL group were significantly
      higher than those of the Al group. Multiple and logistic regression analyses with
      confounding parameters further confirmed that plasma adiponectin was not an
      independent determinant for brain and renal small vessel-related disease.
      CONCLUSION: These findings suggest that the plasma level of adiponectin alone is
      not enough for the risk stratification of cardiovascular disease. Leptin
      resistance associated with skeletal muscle loss in addition to obesity may need
      to be addressed to identify high risk people with high plasma adiponectin levels.

PMID- 24937469
TI  - Cryptic diversity between two Imparfinis species (Siluriformes, Heptapteridae) by
      cytogenetic analysis and DNA barcoding.
AB  - Five Imparfinis mirini and one Imparfinis minutus populations were studied using
      basic cytogenetic and molecular techniques. Cytogenetic analysis showed that I.
      mirini individuals presented the same diploid number 2n=58 (FN=116). However,
      they presented two distinct karyomorphs: karyomorph A (36m+18sm+4st) for the Mogi
      Guacu and Paranapanema basin populations, and karyomorph B (42m+12sm+4st) for the
      Tiete basin populations. I. minutus populations from the Paraiba do Sul basin
      presented a karyotype identical to karyomorph A of I. mirini. C-banding also
      presented distinct patterns, with a greater amount of heterochromatin, most of
      which was pericentromeric and interstitial for karyomorph A I. mirini and I.
      minutus. There was a minor amount of heterochromatin in karyomorph B, most of
      which was terminal and interstitial. Simple and interstitial nucleoli organizer
      regions were located in the biggest metacentric pair of the complement in all
      populations with GC-rich nature, and this location was confirmed by the
      fluorescent in situ hybridization technique with 18S ribosomal DNA with 5S rDNA
      synteny. In molecular analysis by DNA barcoding, two other populations from the
      Tiete basin were added. The phylogram showed that the populations were more
      related to the intrabasin. Cytogenetic resemblance among specimens from distinct
      basins may be the result of either recent convergence or ancestral feature
      retention not followed by mutations in mitochondrial DNA.

PMID- 24937467
TI  - Parental smoking during pregnancy and offspring cardio-metabolic risk factors at
      ages 17 and 32.
AB  - OBJECTIVE: To examine the association of maternal and/or paternal smoking during
      pregnancy with offspring cardio-metabolic risk (CMR) factors at adolescence and
      early adulthood, taking into account socio-demographic, medical and lifestyle
      characteristics of parents and offspring, as well as offspring common genetic
      variation. METHODS: We used a population-based cohort of all 17 003 births in
      Jerusalem during 1974-76, with available archival data on parental and birth
      characteristics. Measurements at age 17 were assessed at military induction
      examinations for 11 530 offspring. 1440 offspring from the original 1974-1976
      birth cohort were sampled using a stratified sampling approach, and were
      interviewed and examined at age 32. Parental smoking during pregnancy (i.e.
      maternal, paternal and any parent) was primarily defined dichotomously (any
      number of cigarettes smoked daily by mother or father during pregnancy vs. non
      smokers). Additionally, smoking was assessed by quantity of cigarettes smoked
      daily. Linear regression models were used to evaluate the associations of
      parental smoking during pregnancy with various offspring CMR factors, after
      controlling for potential confounders and for genetic variation in candidate
      genes. RESULTS: Prevalence of exposure to parental smoking in-utero (i.e. smoking
      of any parent) was 53.2% and 48.4% among the 17 years old and 32 years old
      samples, respectively. At age 17, smoking of at least one parent during pregnancy
      was significantly associated with weight (B = 1.39), height (B = 0.59), BMI (B =
      0.32) and pulse rate (B = -0.78) (p-values < 0.001). At age 32, parental smoking,
      adjusted for covariates, was associated with 2.22 kg higher mean offspring
      weight, 0.95 cm higher mean offspring height, 0.57 kg/m(2) higher BMI, and 1.46
      cm higher waist-circumference (p-values <= 0.02). Similar results, reflecting a
      dose response, were observed when maternal and paternal smokings were assessed by
      number of cigarettes smoked daily. CONCLUSIONS: This prospective study
      demonstrates a potential long-term adverse effect of parental smoking during
      pregnancy on offspring health and calls for increasing efforts to promote smoking
      cessation of both parents before pregnancy.

PMID- 24937468
TI  - Inflammatory profiles in the BTBR mouse: how relevant are they to autism spectrum
      disorders?
AB  - Autism spectrum disorders (ASD) are a group of disorders characterized by core
      behavioral features including stereotyped interests, repetitive behaviors and
      impairments in communication and social interaction. In addition, widespread
      changes in the immune systems of individuals with ASD have been identified, in
      particular increased evidence of inflammation in the periphery and central
      nervous system. While the etiology of these disorders remains unclear, it appears
      that multiple gene and environmental factors are involved. The need for animal
      models paralleling the behavioral and immunological features of ASD is paramount
      to better understand the link between immune system dysregulation and behavioral
      deficits observed in these disorders. As such, the asocial BTBR mouse strain
      displays both ASD relevant behaviors and persistent immune dysregulation,
      providing a model system that has and continues to be instructive in
      understanding the complex nature of ASD. 

PMID- 24937470
TI  - Impedimetric detection of mutant p53 biomarker-driven metastatic breast cancers
      under hyposmotic pressure.
AB  - In cancer cells, the oncogenic mutant p53 (mtp53) protein is present at high
      levels and gain-of-function (GOF) activities with more expression of mtp53
      proteins contribute to tumor growth and metastasis. Robust analytical approaches
      that probe the degree of metastasis of cancer cells in connection with the mtp53
      activity will be extremely useful not only for establishing a better cancer
      prognosis but also understanding the fundamental mechanism of mtp53 oncogenic
      action. Here we assessed the influence of mtp53 in breast cancers to the
      mechanical property of breast cancer cells. Recently, ovarian and kidney cancer
      cell lines have been shown to have higher cellular elasticity as compared to
      normal cells assessed by monitoring the degree of deformation under hyposmotic
      pressure. To make fast detection in large scale, the impedance measurement was
      applied to monitor the swelling ratio of cells with time. The results showed that
      knockdown of mtp53 leads to decrease in cell swelling. In addition, by means of
      two types of impedimetric detection systems we consistently detected enhancement
      of impedance signal in mtp53-expressing breast cancer cells. Based on this
      observation we hypothesize that highly expressed mtp53 in metastatic mutant
      breast cancers can promote tumor progression by making cells more deformable and
      easier to spread out through extracellular matrix. The identification via the
      electric measurement can be accomplished within 10 minutes. All results in this
      report suggest that electric probing for the extent of the mtp53 expression of
      breast cancer cells may serve as a meaningful fingerprint for the cancer
      diagnostics, and this outcome will also have an important clinical implication
      for the development of mtp53-based targeting for tumor detection and treatment. 

PMID- 24937471
TI  - Electrochemical response of metal complexes in homogeneous solution under
      photoirradiation.
AB  - The electrochemical detection of metal complexes in the photoexcited state is
      important for understanding photoinduced electron transfer (PET) processes, which
      play a central role in photo-energy conversion systems. In general, however, the
      redox potentials of excited states have been indirectly estimated by a
      combination of spectroscopic properties and ground-state redox potentials. To
      establish a simple method for directly determining the redox potentials of the
      photoexcited states of metal complexes, electrochemical measurements under
      several conditions were performed. The electrochemical response was largely
      influenced not only by the generation of photoexcited molecules but also by the
      convection induced by photoirradiation, even when the global temperature of the
      sample solution was unchanged. The suppression of these unfavourable
      electrochemical responses was successfully achieved by adopting well-established
      electrochemical techniques. Furthermore, as an initial demonstration, the
      photoexcited state of a Ru-based metal complex was directly detected, and its
      redox potential was determined using a thin layer electrochemical method. 

PMID- 24937472
TI  - Bisecting or not bisecting: this is the neglect question. Line bisection
      performance in the diagnosis of neglect in right brain-damaged patients.
AB  - In the present study we analysed the bisecting behaviour of 287 chronic right
      brain-damaged patients by taking into account the presence and severity of
      extrapersonal and/or personal neglect diagnosed with the hemineglect battery. We
      also analysed right brain-damaged patients who had (or did not have) neglect
      according to their line bisection performance. Our results showed that
      performance of the line bisection task correlates with performance of
      cancellation tasks, reading and perceptual tasks, but not with the presence of
      personal neglect. Personal neglect seems to be unrelated to line bisection
      behaviour. Indeed, patients affected by extrapersonal and personal neglect do not
      show more severe neglect in line bisection than patients with only extrapersonal
      neglect. Furthermore, we observed that 20.56% of the patients were considered
      affected or not by neglect on the line bisection task compared with the other
      spatial tasks of the hemineglect battery. We conclude that using a battery with
      multiple tests is the only way to guarantee a reliable diagnosis and effectively
      plan for rehabilitative training. 

PMID- 24937473
TI  - Index of central obesity as a parameter to replace waist circumference for the
      definition of metabolic syndrome in predicting cardiovascular disease.
AB  - OBJECTIVE: To compare the suitability of metabolic syndrome definitions in
      predicting cardiovascular disease (CVD) risk. METHODS: We analyzed data from a
      population-based prospective cohort of 3598 participants from Jiangsu, China.
      Waist circumference was replaced with central obesity [index of central obesity
      (ICO), a ratio of waist circumference and height] in Cholesterol Education
      Program Adult Treatment Panel III (ICO-replaced ATPIII) and International
      Diabetes Federation (ICO-replaced IDF), respectively. Cox proportional-hazards
      regression model and the receiver operating characteristic curve (ROC curve) was
      used to evaluate the suitability of ATPIII, IDF, ICO-replaced IDF and ICO
      replaced ATPIII in predicting CVD risk. RESULTS: ICO was a better parameter in
      predicting CVD risk by ROC curve analysis. The ROC curve analysis also showed
      that although ICO-replaced IDF and IDF had the higher degree of specificity,
      lower sensitivity, longer ROC curve distance, less area under the curve to
      identify CVD than ATPIII and ICO-replaced ATPIII, therefore ICO-replaced IDF and
      IDF seemed to be undesirable. However, there was no significant difference in
      area under the curve between ATPIII and ICO-replaced ATPIII in predicting CVD
      risk. But it seems that odds ratios for abnormal triglyceride and high-density
      lipoprotein levels increase slightly when using ICO, but decrease for
      hyperglycemia and hypertension when using ICO. CONCLUSION: ICO was a better
      predictor of abnormal triglyceride and high-density lipoprotein levels than waist
      circumference, but waist circumference was a better predictor of hyperglycemia
      and hypertension than ICO. However, we failed to support ICO as a better
      parameter for metabolic syndrome definition in predicting CVD risk compared with
      waist circumference.

PMID- 24937474
TI  - Blood transfusions following trauma: finding an evidence-based vein.

PMID- 24937475
TI  - Electron transfer control in soluble methane monooxygenase.
AB  - The hydroxylation or epoxidation of hydrocarbons by bacterial multicomponent
      monooxygenases (BMMs) requires the interplay of three or four protein components.
      How component protein interactions control catalysis, however, is not well
      understood. In particular, the binding sites of the reductase components on the
      surface of their cognate hydroxylases and the role(s) that the regulatory
      proteins play during intermolecular electron transfer leading to the hydroxylase
      reduction have been enigmatic. Here we determine the reductase binding site on
      the hydroxylase of a BMM enzyme, soluble methane monooxygenase (sMMO) from
      Methylococcus capsulatus (Bath). We present evidence that the ferredoxin domain
      of the reductase binds to the canyon region of the hydroxylase, previously
      determined to be the regulatory protein binding site as well. The latter thus
      inhibits reductase binding to the hydroxylase and, consequently, intermolecular
      electron transfer from the reductase to the hydroxylase diiron active site. The
      binding competition between the regulatory protein and the reductase may serve as
      a control mechanism for regulating electron transfer, and other BMM enzymes are
      likely to adopt the same mechanism. 

PMID- 24937477
TI  - Biogenic copper oxide nanoparticles synthesis using Tabernaemontana divaricate
      leaf extract and its antibacterial activity against urinary tract pathogen.
AB  - This investigation explains the biosynthesis and characterization of copper oxide
      nanoparticles from an Indian medicinal plant by an eco-friendly method. The main
      objective of this study is to synthesize copper oxide nanoparticles from
      Tabernaemontana divaricate leaves through a green chemistry approach. Highly
      stable, spherical copper oxide nanoparticles were synthesized by using 50%
      concentration of Tabernaemontana leaf extract. Formation of copper oxide
      nanoparticles have been characterized by UV-Vis absorption spectroscopy, X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning
      electron microscopy (SEM) with energy dispersive X-ray analysis (EDX) and
      transmission electron microscopy (TEM) analysis. All the analyses revealed that
      copper oxide nanoparticles were 48+/-4nm in size. Functional groups and chemical
      composition of copper oxide were also confirmed. Antimicrobial activity of
      biogenic copper oxide nanoparticles were investigated and maximum zone of
      inhibition was found in 50MUg/ml copper oxide nanoparticles against urinary tract
      pathogen (Escherichia coli). 

PMID- 24937476
TI  - The effect of inhaled IFN-beta on worsening of asthma symptoms caused by viral
      infections. A randomized trial.
AB  - RATIONALE: Ex vivo, bronchial epithelial cells from people with asthma are more
      susceptible to rhinovirus infection caused by deficient induction of the
      antiviral protein, IFN-beta. Exogenous IFN-beta restores antiviral activity.
      OBJECTIVES: To compare the efficacy and safety of inhaled IFN-beta with placebo
      administered to people with asthma after onset of cold symptoms to prevent or
      attenuate asthma symptoms caused by respiratory viruses. METHODS: A total of 147
      people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2
      5), with a history of virus-associated exacerbations, were randomized to 14-day
      treatment with inhaled IFN-beta (n = 72) or placebo (n = 75) within 24 hours of
      developing cold symptoms and were assessed clinically, with relevant samples
      collected to assess virus infection and antiviral responses. MEASUREMENTS AND
      MAIN RESULTS: A total of 91% of randomized patients developed a defined cold. In
      this modified intention-to-treat population, asthma symptoms did not get
      clinically significantly worse (mean change in six-item Asthma Control
      Questionnaire <0.5) and IFN-beta treatment had no significant effect on this
      primary endpoint, although it enhanced morning peak expiratory flow recovery (P =
      0.033), reduced the need for additional treatment, and boosted innate immunity as
      assessed by blood and sputum biomarkers. In an exploratory analysis of the subset
      of more difficult-to-treat, Step 4-5 people with asthma (n = 27 IFN-beta; n = 31
      placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this
      was prevented by IFN-beta (P = 0.004). CONCLUSIONS: Although the trial did not
      meet its primary endpoint, it suggests that inhaled IFN-beta is a potential
      treatment for virus-induced deteriorations of asthma in difficult-to-treat people
      with asthma and supports the need for further, adequately powered, trials in this
      population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).

PMID- 24937478
TI  - Community shifts in the surface microbiomes of the coral Porites astreoides with
      unusual lesions.
AB  - Apical lesions on Porites astreoides were characterized by the appearance of a
      thin yellow band, which was preceded by bleaching of the coral tissues and
      followed by a completely denuded coral skeleton, which often harbored secondary
      macroalgal colonizers. These characteristics have not been previously described
      in Porites and do not match common Caribbean coral diseases. The lesions were
      observed only in warmer months and at shallow depths on the fore reef in Belize.
      Analysis of the microbial community composition based on the V4 hypervariable
      region of 16S ribosomal RNA genes revealed that the surface microbiomes
      associated with nonsymptomatic corals were dominated by the members of the genus
      Endozoicomonas, consistent with other studies. Comparison of the microbiomes of
      nonsymptomatic and lesioned coral colonies sampled in July and September revealed
      two distinct groups, inconsistently related to the disease state of the coral,
      but showing some temporal signal. The loss of Endozoicomonas was characteristic
      of lesioned corals, which also harbored potential opportunistic pathogens such as
      Alternaria, Stenotrophomonas, and Achromobacter. The presence of lesions in P.
      astreoides coincided with a decrease in the relative abundance of Endozoicomonas,
      rather than the appearance of specific pathogenic taxa. 

PMID- 24937479
TI  - Personnel and participant experiences of a residential weight-loss program. A
      qualitative study.
AB  - BACKGROUND: Residential weight-loss programs aim to help persons with obesity
      lose weight and maintain a long-term healthy lifestyle. Knowledge is needed on
      the different actors' perceptions and experiences from such programs. The aim of
      this study was to describe how personnel argued for and perceived a residential
      weight-loss program, to investigate how the participants experienced the program,
      and to contrast these perspectives. METHODS: This qualitative study took place in
      an 18-week residential weight-loss program. Exercise, diet, and personal
      development were the main components in the program. Data was collected through
      participant observation and individual and focus group interviews with
      participants and personnel. RESULTS: Program personnel characterized persons with
      obesity in specific terms, and these formed the basis of the educational aims,
      teaching principles, and content of the program. According to personnel, persons
      with obesity typically had problems acknowledging their own resources, lived
      unstructured lives, had a distorted relationship to food, experienced a range of
      social problems and featured a lack of personal insight. Program participants
      reported enthusiasm about their experiences of exercise and appreciated measures
      of success with the exercise program. They had, however, very different
      experiences regarding the usefulness and appropriateness of the parts of the
      program focused on social and personal development. Some felt that weight loss
      required an engagement with personal development while others viewed it as
      unnecessary and inappropriate. CONCLUSION: The reliance in personnel accounts on
      particular characteristics of persons with obesity as a rationale for the program
      might lead to stigmatizing and stereotyping. Program activities focused on social
      and personal development need to be better understood by participants if they are
      to be viewed as helpful. To achieve this personnel must carefully consider how
      these parts of the program are communicated and conducted.

PMID- 24937480
TI  - Diminished hERG K+ channel activity facilitates strong human labour contractions
      but is dysregulated in obese women.
AB  - Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac
      action potential and contraction duration. Human uterine contractions are
      underpinned by an action potential that also possesses an initial spike followed
      by prolonged depolarization. Here we show that hERG channel proteins (alpha
      conducting and beta-inhibitory subunits) and hERG currents exist in isolated
      patch-clamped human myometrial cells. We show that hERG channel activity
      suppresses contraction amplitude and duration before labour, thereby facilitating
      quiescence. During established labour, expression of beta-inhibitory protein is
      markedly enhanced, resulting in reduced hERG activity that is associated with an
      increased duration of uterine action potentials and contractions. Thus, changes
      in hERG channel activity contribute to electrophysiological mechanisms that
      produce contractions during labour. We also demonstrate that this system fails in
      women with elevated BMI, who have enhanced hERG activity as a result of low beta
      inhibitory protein expression, which likely contributes to the weak contractions
      and poor labour outcomes observed in many obese women necessitating caesarean
      delivery. 

PMID- 24937481
TI  - Conversion from robotic surgery to laparotomy: a case-control study evaluating
      risk factors for conversion.
AB  - OBJECTIVES: To determine risk factors associated with conversion to laparotomy
      for women undergoing robotic gynecologic surgery. METHODS: The medical records of
      459 consecutive robotic surgery cases performed between December 2006 and October
      2011 by 8 different surgeons at a single institution were retrospectively
      reviewed. Cases converted to laparotomy were compared to those completed
      robotically. Descriptive statistics were used to summarize the demographic and
      clinical characteristics. RESULTS: Forty of 459 (8.7%, 95% CI 6.3%-11.7%)
      patients had conversion to open surgery. Reason for conversion included poor
      visualization due to adhesions (13), inability to tolerate Trendelenburg (7),
      enlarged uterus (7), extensive peritoneal disease (5), bowel injury (2), ureteral
      injury (1), vascular injury (1), bladder injury (1), technical difficulty with
      the robot (2), and inability to access abdominal cavity (1). 5% of cases were
      converted prior to docking the robot. On univariate analysis, preoperative
      diagnosis (p=0.012), non-White race (p=0.004), history of asthma (p=0.027), ASA
      score (p=0.032), bowel injury (p=0.012), greater BMI (p<0.001), need for blood
      transfusion (p<0.001), and expected blood loss (p<0.001) were associated with
      conversion. On multivariate analysis, non-White race (OR 2.88, 95% CI 1.39-5.96,
      p=0.004), bowel injury (OR 35.40, 95% CI 3.00-417.28, p=0.005), and increasing
      BMI (OR 1.06, 95% CI 1.03-1.09, p<0.001) were significantly associated with
      increased risk for conversion. Prior surgery was not associated with conversion
      to open surgery (p=0.347). CONCLUSION: Conversion to laparotomy was required for
      8.7% of patients undergoing robotic surgery for a gynecologic indication.
      Increasing BMI and non-white race were identified as the two preoperative risk
      factors associated with conversion.

PMID- 24937482
TI  - Impact of intra-aortic balloon pumping on hypotension and outcomes in acute right
      ventricular infarction.
AB  - OBJECTIVES: This study investigated the immediate hemodynamic effects of intra
      aortic balloon pump (IABP) support and clinical outcomes in patients with acute
      right ventricular infarction (RVI) complicated by hypotension. BACKGROUND: IABP
      improves hypotension in patients with acute myocardial infarction and left
      ventricular shock, but the effects have not been well studied in acute RVI with
      predominant right ventricular shock. METHODS: We retrospectively analyzed
      hemodynamics and clinical outcomes in 32 patients with acute inferior ST
      elevation myocardial infarction complicated by RVI, in whom hypotension requiring
      IABP placement developed despite intact left ventricular ejection fraction.
      RESULTS: Pre-IABP hypotension was present in all (100%) patients, and in every
      case IABP augmentation increased mean arterial pressure (55.9+/-7.4 to 76.8+/
      14.7 mmHg, P<0.0001). Adverse clinical events included respiratory distress
      requiring intubation in 46.9%, cardiopulmonary resuscitation in 25%, episodes of
      ventricular tachycardia/fibrillation in 56.3%, and transvenous pacemaker
      placement in 56.3% of patients. There were six inhospital deaths (18.8%). Pre
      IABP hemodynamics were similar in those patients who survived to discharge
      compared with those who died. However, in those patients who died, there was
      significantly lower augmentation of peak systolic blood pressure during IABP
      support compared with survivors (2.7+/-17 vs. 27+/-22 mmHg, P<0.015). CONCLUSION:
      IABP support results in immediate hemodynamic improvement in patients with acute
      RVI complicated by shock. The majority of these shock patients survived and the
      magnitude of mean arterial pressure and peak systolic blood pressure augmentation
      may impart prognostic value.

PMID- 24937484
TI  - Photoelectron spectroscopic and computational study of hydrated pyrimidine
      anions.
AB  - The stabilization of the pyrimidine anion by the addition of water molecules is
      studied experimentally using photoelectron spectroscopy of mass-selected hydrated
      pyrimidine clusters and computationally using quantum-mechanical electronic
      structure theory. Although the pyrimidine molecular anion is not observed
      experimentally, the addition of a single water molecule is sufficient to impart a
      positive electron affinity. The sequential hydration data have been used to
      extrapolate to -0.22 eV for the electron affinity of neutral pyrimidine, which
      agrees very well with previous observations. These results for pyrimidine are
      consistent with previous studies of the hydrated cluster anions of uridine,
      cytidine, thymine, adenine, uracil, and naphthalene. This commonality suggests a
      universal effect of sequential hydration on the electron affinity of similar
      molecules. 

PMID- 24937486
TI  - Assessing the impact of human activities on British Columbia's estuaries.
AB  - The world's marine and coastal ecosystems are under threat and single-sector
      management efforts have failed to address those threats. Scientific consensus
      suggests that management should evolve to focus on ecosystems and their human,
      ecological, and physical components. Estuaries are recognized globally as one of
      the world's most productive and most threatened ecosystems and many estuarine
      areas in British Columbia (BC) have been lost or degraded. To help prioritize
      activities and areas for regional management efforts, spatial information on
      human activities that adversely affect BC's estuaries was compiled. Using
      statistical analyses, estuaries were assigned to groups facing related threats
      that could benefit from similar management. The results show that estuaries in
      the most populated marine ecosections have the highest biological importance but
      also the highest impacts and the lowest levels of protection. This research is
      timely, as it will inform ongoing marine planning, land acquisition, and
      stewardship efforts in BC. 

PMID- 24937483
TI  - Effectiveness of guided and unguided low-intensity internet interventions for
      adult alcohol misuse: a meta-analysis.
AB  - BACKGROUND: Alcohol misuse ranks within the top ten health conditions with the
      highest global burden of disease. Low-intensity, Internet interventions for
      curbing adult alcohol misuse have been shown effective. Few meta-analyses have
      been carried out, however, and they have involved small numbers of studies,
      lacked indicators of drinking within low risk guidelines, and examined the
      effectiveness of unguided self-help only. We therefore conducted a more thorough
      meta-analysis that included both guided and unguided interventions. METHODS:
      Systematic literature searches were performed up to September 2013. Primary
      outcome was the mean level of alcohol consumption and drinking within low risk
      guidelines for alcohol consumption at post-treatment. FINDINGS: We selected 16
      randomised controlled trials (with 23 comparisons and 5,612 participants) for
      inclusion. Results, showed a small but significant overall effect size in favour
      of Internet interventions (g = 0.20, 95% CI: 0.13-0.27, p<.001). Participants in
      Internet interventions drunk on average 22 grams of ethanol less than controls
      and were significantly more likely to be adhering to low-risk drinking guidelines
      at post-treatment (RD 0.13, 95% CI: 0.09-0.17, p<.001). Subgroup analyses
      revealed no significant differences in potential moderators for the outcome of
      alcohol consumption, although there was a near-significant difference between
      comparisons with waitlist control and those with assessment-only or alcohol
      information control conditions (p = .056). CONCLUSIONS: Internet interventions
      are effective in reducing adult alcohol consumption and inducing alcohol users to
      adhere to guidelines for low-risk drinking. This effect is small but from a
      public health point of view this may warrant large scale implementation at low
      cost of Internet interventions for adult alcohol misuse. Moderator analyses with
      sufficient power are, however, needed in order to assess the robustness of these
      overall results and to assess whether these interventions may impact on subgroups
      with different levels of success.

PMID- 24937487
TI  - The importance of atmospheric base cation deposition for preventing soil
      acidification in the Athabasca Oil Sands Region of Canada.
AB  - Industrial activities in the oil sands region of Alberta, Canada have resulted in
      greatly elevated emissions of SO2 and N (NO(x) and NH3) and there are concerns
      over possible widespread ecosystem acidification. Acid sensitive soils in the
      region are common and have very low base cation weathering rates: the median base
      cation weathering rate estimated for 63 sites using PROFILE was just 17 mmol cm(
      2) yr(-1). Deposition of S and N in throughfall was approximately twice as high
      as deposition measured with open collectors and could be as high as 360 mmol cm(
      2) yr(-1) within 20 km of the main industrial center, although deposition
      declined logarithmically with distance from the industrial activities. Base
      cation deposition however, mostly exceeded the combined inputs of S and N in bulk
      deposition and throughfall, particularly during the summer months. The potential
      for soil acidification at a site close (<3 km) to the largest mine was assessed
      using the dynamic ecosystem acidification model, MAGIC (Model of Acidification of
      Groundwater in Catchments). Despite very low base cation weathering rates (~6
      mmol cm(-2) yr(-1)) and high (~250 mmol cm(-2) yr(-1)) acid (S+N) deposition at
      the site, soil base saturation and soil solution pH and molar Ca:Al ratio were
      predicted to increase in the future assuming acid and base cation deposition
      constant at current rates. This work shows that despite extremely low soil base
      cation weathering rates in the region, the risk of soil acidification is
      mitigated to a large extent by high base cation deposition, which in contrast to
      S emissions is derived from fugitive dust sources in the mines, and is poorly
      quantified for regional modeling studies.

PMID- 24937489
TI  - Levels and profiles of POPs (organochlorine pesticides, PCBs, and PAHs) in free
      ranging common bottlenose dolphins of the Canary Islands, Spain.
AB  - The effect of anthropogenic pollution in marine mammals worldwide has become an
      important issue due to the high concentrations found in many areas. The present
      study represents the first report of pollutants in free-ranging cetaceans from
      the Canary Islands, where there are 12 marine Special Areas of Conservation
      (SACs), because of the presence of bottlenose dolphins (Tursiops truncatus). We
      selected this resident population of dolphins as a bioindicator to gain knowledge
      concerning the toxicological status of the cetaceans of this protected area. In
      64 biopsy samples of live free-ranging animals sampled from 2003 to 2011, we
      determined the concentrations of 18 polychlorinated biphenyls (PCBs), 23
      organochlorine pesticides (OCPs) and 16 polycyclic aromatic hydrocarbons (PAHs).
      We found high levels of many of these pollutants, and some of them were
      detectable in 100% of the samples. The median value for ?OCPs was 57,104 ng g(-1)
      lipid weight (lw), and the dichlorodiphenyldichloroethylene (p,p'-DDE) accounted
      for 70% of this amount. Among PCBs, congeners 180, 153 and 138 were predominant
      (82% of ?PCBs; median = 30,783 ng g(-1) lw). Concerning the analyzed PAHs, the
      total median burden was 13,598 ng g(-1) lw, and phenanthrene was the compound
      measured at the highest concentration followed by pyrene and by naphthalene.
      Surprisingly, we have found that organohalogen pollutants exhibit an upward trend
      in recent years of sampling. Thus, according to the guidelines outlined in the
      EU's Marine Strategy Framework Directive, further monitoring studies in Canary
      Islands are required to contribute to the conservation of the resident
      populations of marine mammals in this region.

PMID- 24937488
TI  - Combined effects of aqueous suspensions of fullerene and humic acid on the
      availability of polycyclic aromatic hydrocarbons: evaluated with negligible
      depletion solid-phase microextraction.
AB  - The wide application of engineered carbon nanomaterials, such as fullerene (C60),
      will inevitably result in their introduction into the aqueous environment.
      Interactions of C60 with abundant natural organic matter (NOM) will likely alter
      the bioavailability of organic compounds to aquatic organisms. The availability
      of 12 types of polycyclic aromatic hydrocarbons (PAHs) in various aqueous
      suspensions of fullerene (nC60) prepared by different methods, e.g., in humic
      acid (HA) and particularly in combined systems of nC(60) and HA, was investigated
      by negligible depletion solid-phase microextraction (nd-SPME). The results showed
      that HA accelerated the rate constants (k2) of almost all PAH uptakes to the nd
      SPME fibers compared with the solutions without the matrix; the combined matrices
      of nC(60) and HA significantly promoted the k2 of highly hydrophobic PAHs (logKOW
      5.81-6.20), whereas they retarded that of less hydrophobic ones (logKOW 3.82
      4.63) (p<0.05). Remarkable or minor reduction of free concentration of PAH was
      observed in the combined system of nC(60) and HA depending on the properties of
      individual PAHs. Sorption coefficients (KHA, K(C60) and K(C60+HA)) of various
      PAHs in different matrices were provided, and matrix concentrations showed no
      significant effects. For highly hydrophobic PAHs (logKOW 5.16-6.20), the
      logK(C60+HA) >= logKHA > logK(C60), whereas for less hydrophobic PAHs (logKOW 3.8
      4.63), the Kmatrix values in various matrices showed no noticeable trend. In
      addition, higher K(C60) values were obtained for aqu/nC(60) than for son/nC(60)
      for most highly hydrophobic PAHs. The above results suggest that hydrophobicity
      plays an important role in determining Kmatrix in addition to the matrix effects.
      The interactions between nC(60) and HA have critical or minor impacts on
      availability, and thus bioavailability, of PAHs. This paper contributes to the
      understanding of the bioavailability mechanisms of organic pollutants in the
      aquatic environment with both nC(60) and NOM.

PMID- 24937490
TI  - Impact of forecasted changes in Polish economy (2015 and 2020) on nutrient
      emission into the river basins.
AB  - Poland, with its large drainage area, with 50% contribution of agricultural land
      and 45% contribution of population to overall agricultural land area and
      population number in the Baltic catchment, is the largest exporter of riverine
      nitrogen (N) and phosphorus (P) to the sea. The economic transition has resulted
      in substantial, statistically significant decline in N, P export from Polish
      territory to the Baltic Sea. Following the obligations arising from the Helsinki
      Commission (HELCOM) declarations, in the coming years, Poland is expected to
      reduce riverine N loads by ca. 25% and P loads by ca. 60% as referred to the
      average flow normalized loads recorded in 1997-2003. The aim of this paper is to
      estimate annual source apportioned N and P emissions into these river basins in
      2015 and 2020 with application of modeling studies (MONERIS). Twelve scenarios,
      encompassing changes in anthropogenic (diffuse, point source) and natural
      pressure (precipitation, water outflow due to climate change), have been applied.
      Modeling outcome for the period 2003-2008 served as our reference material. In
      applied scenarios, N emission into the Oder basin in 2015 and 2020 shows an
      increase from 4.2% up to 9.1% as compared with the reference period. N emission
      into the Vistula basin is more variable and shows an increase by max. 17.8% or a
      decrease by max. 4.7%, depending on the scenario. The difference between N
      emission into the Oder and Vistula basins is related to the catchment
      peculiarities and handling of point sources emission. P emission into both basins
      shows identical scenario patters and a maximum decrease reaches 17.8% in the Oder
      and 16.7% in the Vistula basin. Despite a declining tendency in P loads in both
      rivers in all the scenarios, HELCOM targeted P load reduction is not feasible. 

PMID- 24937491
TI  - Using fuzzy logic analysis for siting decisions of infiltration trenches for
      highway runoff control.
AB  - Determining optimal locations for best management practices (BMPs), including
      their field considerations and limitations, plays an important role for effective
      stormwater management. However, these issues have been often overlooked in
      modeling studies that focused on downstream water quality benefits. This study
      illustrates the methodology of locating infiltration trenches at suitable
      locations from spatial overlay analyses which combine multiple layers that
      address different aspects of field application into a composite map. Using seven
      thematic layers for each analysis, fuzzy logic was employed to develop a site
      suitability map for infiltration trenches, whereas the DRASTIC method was used to
      produce a groundwater vulnerability map on the island of Oahu, Hawaii, USA. In
      addition, the analytic hierarchy process (AHP), one of the most popular overlay
      analyses, was used for comparison to fuzzy logic. The results showed that the AHP
      and fuzzy logic methods developed significantly different index maps in terms of
      best locations and suitability scores. Specifically, the AHP method provided a
      maximum level of site suitability due to its inherent aggregation approach of all
      input layers in a linear equation. The most eligible areas in locating
      infiltration trenches were determined from the superposition of the site
      suitability and groundwater vulnerability maps using the fuzzy AND operator. The
      resulting map successfully balanced qualification criteria for a low risk of
      groundwater contamination and the best BMP site selection. The results of the
      sensitivity analysis showed that the suitability scores were strongly affected by
      the algorithms embedded in fuzzy logic; therefore, caution is recommended with
      their use in overlay analysis. Accordingly, this study demonstrates that the
      fuzzy logic analysis can not only be used to improve spatial decision quality
      along with other overlay approaches, but also is combined with general water
      quality models for initial and refined searches for the best locations of BMPs at
      the sub-basin level. 

PMID- 24937493
TI  - Conservation of prehistoric caves and stability of their inner climate: lessons
      from Chauvet and other French caves.
AB  - In the last 150 years, some prehistoric painted caves suffered irreversible
      degradations due to misperception of conservation issues and subsequent
      mismanagement. These sites presented naturally an exceptional stability of their
      internal climate allowing conservation in situ of outstanding fragile remains,
      some for nearly 40,000 years. This is for a large part due to exchanges of air,
      CO2, heat and water with the karstic system in which these caves are included. We
      introduce the concept of underground confinement, based on the stability of the
      inner cave climate parameters, especially its temperature. Confined caves present
      the best conservative properties. It is emphasized that this confined state
      implies slow exchanges with the surrounding karst and that a stable cave cannot
      be viewed as a closed system. This is illustrated on four case studies of French
      caves of various confinement states evidenced by long term continuous monitoring
      and on strategies to improve their conservation properties. The Chauvet cave
      presents optimal conservation properties. It is wholly confined as shown by the
      stability of its internal parameters since its discovery in 1994. In Marsoulas
      cave, archeological works removed the entrance scree and let a strong opening
      situation of the decorated zone. Remediation is expected by adding a buffer
      structure at the entrance. In Pech Merle tourist cave, recurrent painting fading
      was related to natural seasonal drying of walls. Improvement of the cave closure
      system restored a confined state insuring optimal visibility of the paintings. In
      Gargas tourist cave, optimization of closures, lighting system and number of
      visitors, allowed it to gradually reach a semi-confined state that improved the
      conservation properties. Conclusions are drawn on the characterization of
      confinement state of caves and on the ways to improve their conservation
      properties by restoring their initial regulation mechanisms and to avoid threats
      to their stability.

PMID- 24937492
TI  - A framework for the assessment of the environmental risk posed by pharmaceuticals
      originating from hospital effluents.
AB  - The consumption of pharmaceuticals is increasing in both hospitals and
      households. After administration, many compounds enter the water cycle as parent
      compounds or their metabolites via excretion. Conventional municipal wastewater
      treatment plants are unable to efficiently remove all the different compounds
      found in sewage and, consequently, treated effluents are one of the main sources
      of persistent micropollutants in the environment. Hospital patients are
      administered relatively high quantities of drugs and therefore hospital
      wastewaters can consistently contribute to treatment plant influent loads, with
      the magnitude of environmental risk posed by pharmaceuticals originating from
      hospital effluents largely unknown. This study has therefore developed a
      framework to enable authorities responsible for hospital management and
      environmental health to evaluate such risk, considering site-specific information
      such as the contribution of human population and hospital sizes, wastewater
      treatment removal efficiency, and potential dilution in the receiving water body.
      The framework was applied to three case studies, that are representative of
      frequent situations in many countries, and findings demonstrated that the degree
      of risk posed by any compound was site-specific and depended on a combination of
      several factors: compound concentration and toxicity, compound removal efficiency
      in the wastewater treatment plant and dilution factor. Ofloxacin, 17alpha
      ethinylestradiol, erythromycin and sulfamethoxazole were identified as compounds
      of concern and might require management in order to reduce risk. 

PMID- 24937494
TI  - Acute effects of diurnal temperature range on mortality in 8 Chinese cities.
AB  - Diurnal temperature range (DTR) is a meteorological indicator closely associated
      with global climate change. There have been no multicity studies in China
      addressing the DTR-related health impact. We hypothesized that an increase of DTR
      is associated with higher daily mortality with a potential lag of effect, and
      investigated the acute effects of DTR on total, cardiovascular, and respiratory
      mortality in 8 large Chinese cities from 2001 to 2010. We first calculated city
      specific effect of DTR in the full year, the cool season (November to the next
      April) and the warm season (May to October) separately using a semi-parametric
      generalized additive model; then we pooled the city-specific estimates with meta
      analysis. After adjusting for long-term and seasonal trends, temperature,
      relative humidity and air pollution levels, we found statistically significant
      associations between DTR and daily mortality, especially in cool seasons. A 1 
      degrees C increment of DTR on lag-day 1 corresponded to a 0.42% (95% CI, 0.14 to
      0.70) increase in total non-accidental mortality, 0.45% (95% CI, 0.26 to 0.65)
      increase in cardiovascular mortality, and a 0.76% (95% CI, 0.24 to 1.29) increase
      in respiratory mortality in cool seasons. Deaths among females and elderly (>= 65
      years) were more strongly associated with DTR than among males and younger people
      (<65 years). Our analysis suggests that DTR is a potential trigger for death in
      China. Our findings may have important implications for the climate policies in
      the country.

PMID- 24937495
TI  - Accelerated stone deterioration induced by forest clearance around the Angkor
      temples.
AB  - The present study provides the first quantitative assessment of the deteriorative
      impact of forest clearance on susceptible sandstone masonries. At Ta Keo, a
      1000yr-old temple cleared of the Angkor forest in the early 20th century, GIS
      based analysis of historic imagery indicates an average ten-fold increase in
      stone loss rates (0.2 instead of 0.02% per year). This accelerated decay is
      assigned to the climatic stress provoked by the exposure of fragile ornamented
      sandstones to the harsh impact of tropical sunshine and monsoon rains.
      Comparative climate monitoring with the Beng Mealea temple, still located in a
      forested environment, suggests a three-fold post-clearance increase in daily
      temperature and humidity ranges, which is conducive to enhanced swelling
      shrinking movements responsible for accelerated sandstone contour scaling.
      Comparative visual assessment based on a customised 7-point scale of mechanical
      weathering confirms the protective role of canopy, with 79% of decorative motifs
      still almost free of mechanical weathering in the forest (against 7% at the
      cleared site). Disruption of archaeological structures by roots of individual
      trees can be locally observed at Angkor, but this does not negate the dominant
      overall buffering function of the forest cover. At Angkor and other cultural
      heritage sites, this bioprotective 'umbrella effect' should be considered as a
      valuable ecosystem service to be taken into account when defining and
      implementing strategies of sustainable management. 

PMID- 24937496
TI  - Source identification and potential ecological risk assessment of heavy metals in
      PM2.5 from Changsha.
AB  - The probable sources and potential ecological risks of Cu, Zn, Cd and Pb in PM2.5
      in Changsha were analyzed. The intelligent medium-flow total suspended particle
      sampler was used to collect the PM2.5 samples from Yuelu (YL), Kaifu (KF), and
      Yuhua (YH) districts of Changsha in March-April of 2013. The total concentration
      of heavy metals (HMs) in PM2.5 was used for source identification by correlation
      coefficients and principal component analysis (PCA). Otherwise the potential
      ecological risks indices (RIs) were calculated based on the bioavailable
      fractions of HMs which were obtained through BCR sequential extraction. Almost
      50% of Cu, Cd and Pb in PM2.5 of all sites were accumulated in soluble and
      reducible fractions by speciation analysis. The correlation coefficients and PCA
      analysis showed that HMs in PM2.5 of Changsha in spring were mainly from
      vehicular emissions, fuel combustion, resuspension of dust and other pollution
      sources. The average potential ecological RIs of HMs in PM2.5 of Changsha were
      6193.80 which suggests that HMs in PM2.5 was extremely serious. These results
      would be a good reference for health studies and formulation of environmental
      regulations. 

PMID- 24937497
TI  - Diversity of an aerial phototrophic coating of historic buildings in the former
      Auschwitz II-Birkenau concentration camp.
AB  - Aerial phototrophs colonize materials of anthropogenic origin, thus contributing
      to their biodeterioration. Structures preserved at the former Auschwitz II
      Birkenau concentration and extermination camp show signs of degradation by
      cyanobacteria and algae. In order to protect the Auschwitz-Birkenau Memorial
      Site, diversity of aerial phototrophs growing on the historic buildings has been
      studied. Analyses of cyanobacterial and algal biofilms growing on various
      construction substrates were carried out in summer and winter. Multivariate data
      analyses were used to: characterize the diversity of cyanobacteria and algae
      growing in brick and wooden camp buildings depending on the research season,
      indicate preferences of cyanobacteria and algae in colonizing substrates, and to
      predict the environmental factor that most determines the growth of phototrophs.
      The biofilms were formed mainly by cyanobacteria, green algae and diatoms. The
      amount of cyanobacteria and algae in the biofilms was varied, which resulted from
      changes in climatic conditions, the type of substrate and the height at which the
      biofilms developed. In the summer, the ratio of cyanobacteria and algae groups
      was balanced, while in the winter, green algae and diatoms were dominant. Green
      algae showed a preference for colonizing plaster, wood and concrete, of which the
      walls and doors of the buildings were made. Their participation was correlated
      with a height gradient. Cyanobacteria and diatoms grew on bricks and soil on the
      floor of the buildings and temperature and relative humidity were the factors
      that modified their amount. Green algae were more cosmopolitan-occurred in dry
      places, potentially inaccessible to other organisms; therefore, they have been
      identified as the pioneer group in the prevailing climatic conditions. 

PMID- 24937498
TI  - Assessment of agro-industrial and composted organic wastes for reducing the
      potential leaching of triazine herbicide residues through the soil.
AB  - In this study, we examined the effect of four different organic wastes--composted
      sheep manure (CSM), spent coffee grounds (SCG), composted pine bark (CPB) and
      coir (CR)--on the sorption, persistence and mobility of eight symmetrical and two
      asymmetrical-triazine herbicides: atrazine, propazine, simazine, terbuthylazine
      (chlorotriazines), prometon (methoxytriazine), prometryn, simetryn, terbutryn
      (methylthiotriazines), metamitron and metribuzin (triazinones). The downward
      movement of herbicides was monitored using disturbed soil columns packed with a
      clay loam soil (Hipercalcic calcisol) under laboratory conditions. For unamended
      and amended soils, the groundwater ubiquity score (GUS) was calculated for each
      herbicide on the basis of its persistence (as t1/2) and mobility (as KOC). All
      herbicides showed medium/high leachability through the unamended soils. The
      addition of agro-industrial and composted organic wastes at a rate of 10% (w:w)
      strongly decreased the mobility of herbicides. Sorption coefficients normalized
      to the total soil organic carbon (KOC) increased in the amended soils. These
      results suggest that used organic wastes could be used to enhance the retention
      and reduce the mobility of the studied herbicides in soil.

PMID- 24937499
TI  - Pharmacological treatments for acute respiratory distress syndrome: systematic
      review.
AB  - BACKGROUND: Our objective was to systematically review the effect of
      pharmacological therapies on mortality in patients with acute respiratory
      distress syndrome (ARDS), focusing on randomized controlled trials (RCTs)
      published since a previous review in 2004. METHODS: We updated previous searches
      and searched OVID versions of MEDLINE, EMBASE and CENTRAL (to January 2013) and
      proceedings from conferences and bibliographies of included studies. We included
      RCTs of pharmacologic therapies compared with placebo or no therapy for adult
      patients with ARDS, using authors' definitions, which reported on mortality (<= 3
      months after randomization). We excluded subgroups of patients with ARDS reported
      in RCTs enrolling other populations and RCTs of therapies to prevent ARDS,
      nutritional or fluid interventions, inhaled nitric oxide, therapies coupled to a
      mechanical ventilation strategy, or oxygen. Two reviewers independently screened
      citations, selected articles for inclusion, and abstracted clinical and
      methodological data from included studies with disagreements resolved by a third
      reviewer. Mortality data were pooled using random-effects models. RESULTS: From
      13461 citations, 58 trials (6635 patients) of 21 classes of medications met
      selection criteria; 26 trials (3880 patients) were published after 2003. Meta
      analyses showed reduced 28-day mortality with a 48-hour infusion of cis
      atracurium in early ARDS (relative risk 0.66, 95% confidence interval 0.50 to
      0.87; 431 patients, 138 deaths). There was no effect on mortality with
      granulocyte-macrophage colony stimulating factor, late low-dose
      methylprednisolone, neutrophil elastase inhibitors, intravenous salbutamol,
      surfactant, or N-acetylcysteine; each meta-analysis included >= 1 trial published
      after 2003. Seven single trials of other treatments published after 2003 showed
      no effect. Meta-analysis of older trials of prostaglandin E1 also showed no
      effect. CONCLUSION: Effective pharmacotherapy for ARDS remains extremely limited.
      Cis-atracurium is a promising treatment for early moderate-severe ARDS (using
      Berlin definition nomenclature) and merits further investigation in a large RCT.

PMID- 24937500
TI  - Optimal technique for deep breathing exercises after cardiac surgery.
AB  - Cardiac surgery patients often develop a restrictive pulmonary impairment and gas
      exchange abnormalities in the early postoperative period. Chest physiotherapy is
      routinely prescribed in order to reduce or prevent these complications. Besides
      early mobilization, positioning and shoulder girdle exercises, various breathing
      exercises have been implemented as a major component of postoperative care. A
      variety of deep breathing maneuvres are recommended to the spontaneously
      breathing patient to reduce atelectasis and to improve lung function in the early
      postoperative period. Different breathing exercises are recommended in different
      parts of the world, and there is no consensus about the most effective breathing
      technique after cardiac surgery. Arbitrary instructions are given, and
      recommendations on performance and duration vary between hospitals. Deep
      breathing exercises are a major part of this therapy, but scientific evidence for
      the efficacy has been lacking until recently, and there is a lack of trials
      describing how postoperative breathing exercises actually should be performed.
      The purpose of this review is to provide a brief overview of postoperative
      breathing exercises for patients undergoing cardiac surgery via sternotomy, and
      to discuss and suggest an optimal technique for the performance of deep breathing
      exercises. 

PMID- 24937501
TI  - Basic considerations for determining the amount of press fit in acetabular cup
      endoprostheses as a function of the elastic bone behavior.
AB  - Acetabular cup endoprostheses are frequently placed in pelvic bone, employing the
      mechanical principle of press fit. While a sufficiently stable bone-implant
      connection is desirable, deformation of the cup and fracture of the pelvis should
      be avoided. The goal of this work is to demonstrate the importance of the elastic
      properties of bone on the amount of press fit achievable in a specific situation.
      On the basis of previous work describing the relation between relative bone
      mineral density and relative elastic modulus for cortical and trabecular bone,
      mechanical equations were used for analyzing the press-fit loading situation of
      an acetabular cup. Additionally, a two-dimensional finite element model was used
      for visualizing the stress and strain situation in the host bone occurring as a
      consequence of implant insertion, as well as the effect of moment loads acting on
      the acetabular cup. Given the fact that oversizing the implant for a specific
      recipient site is the only clinical means of optimizing press fit, knowledge of
      the elastic properties of the host bone before implant selection would be
      beneficial. Such information could, for instance, be derived from intraoperative
      compressive testing of the host bone.

PMID- 24937502
TI  - Predicting fetal growth deviation in parous women: combining the birth weight of
      the previous pregnancy and third trimester ultrasound scan.
AB  - AIM: To investigate the value of the birth weight of the previous pregnancy (BW1)
      alone and combined with the third trimester ultrasonographically estimated fetal
      weight (EFW) and Doppler studies in the prediction of small (SGA) and large for
      gestational age (LGA) neonates in the index pregnancy (BW2). METHOD: Some 1298
      parous women with uncomplicated singleton pregnancies who had a third trimester
      ultrasound scan were considered as samples in this retrospective cohort study.
      Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle
      cerebral artery pulsatility indices were investigated as predictors of SGA and
      LGA. RESULTS: BW1, maternal weight, mode of conception, and smoking status were
      associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37).
      The addition of EFW conferred significant improvement (R2=0.63), whereas the
      addition of the Doppler indices did not. The sensitivity of BW1 alone in the
      prediction of SGA was 75% for 25% screen positive rate and increased to 92% with
      the addition of EFW. The equivalent figures for LGA were 68% and 93%,
      respectively. CONCLUSIONS: BW1 used as a continuous variable is predictive of
      growth deviations in the index pregnancy. Incorporating EFW enhanced the
      sensitivity for the detection of both conditions.

PMID- 24937503
TI  - Sarcoidosis and pregnancy: obstetrical and neonatal outcomes in a population
      based cohort of 7 million births.
AB  - OBJECTIVES: Data on sarcoidosis in pregnancy is sparse and limited to a few case
      reports and series. Our aim is to determine the prevalence of sarcoidosis at
      delivery, and related maternal and newborn outcomes. STUDY DESIGN: Using the
      United States Healthcare Cost and Utilization Project Nationwide Inpatient Sample
      (HCUP-NIS) from 2003 to 2010, we conducted a population-based retrospective
      cohort study to compare women with and without sarcoidosis at delivery. We
      calculated the prevalence of sarcoidosis in pregnancy and used logistic
      regression analyses to estimate the associated risks of maternal and neonatal
      outcomes. RESULTS: There were 678 cases of sarcoidosis in 7,094,400 births over
      an 8-year period for an overall prevalence of nine and six-tenths cases per
      100,000 births. Compared with controls, women with sarcoidosis were older, more
      likely to be African American and to report being smokers. Women with sarcoidosis
      were more likely to have preeclampsia odds ratio (OR) 1.62 (95% CI 1.18-2.22),
      eclampsia OR 5.27 (95% CI 1.69-16.40), deep vein thrombosis OR 4.92 (95% CI 1.58
      15.33), pulmonary embolism OR 6.68 (95% CI 3.99-11.21), and premature delivery OR
      1.73 (95% CI 1.40-2.15). There was also an increased risk of cesarean deliveries
      and postpartum hemorrhages. There were no cases of maternal death reported.
      CONCLUSIONS: Sarcoidosis in pregnancy is a rare disease associated with an
      increased risk of adverse obstetrical outcomes. Women with sarcoidosis can carry
      out successful pregnancies, however should be made aware of the higher risk of
      adverse events. Given the higher risk of venous thromboembolic events,
      consideration should be given to thromboprophylaxis in pregnancy.

PMID- 24937504
TI  - Use of the angle of progression on ultrasonography to predict spontaneous onset
      of labor within 7 days.
AB  - OBJECTIVE: To investigate the relationship between angle of progression (AoP) on
      ultrasonography at 37-40 weeks' gestation and delivery within 7 days. METHODS:
      This prospective study was conducted between January 2013 and May 2013 at Korea
      University Guro Hospital, Korea. Nulliparous women between 37/0 and 40/3 weeks'
      gestation with a singleton fetus, intact membrane, and cephalic presentation from
      January 2013 to May 2013 were enrolled. To evaluate the cervical parameters of
      cervical length and AoP, transvaginal and transperineal ultrasonography were
      performed, respectively. We then assessed the relationship between cervical
      parameters and onset of labor within 7 days by multivariate logistic regression
      analysis. RESULTS: Women who underwent spontaneous onset of labor within 7 days
      had a significantly shorter cervical length and AoP than those who underwent
      labor after 7 days. Logistic regression analysis showed that a larger AoP was an
      independent predictor of spontaneous labor within 7 days. CONCLUSIONS: A larger
      AoP was significantly associated with spontaneous onset of labor within 7 days.
      These findings may be useful for counseling patients regarding the management of
      term pregnancies.

PMID- 24937505
TI  - Intestinal permeability in patients with metastatic colon cancer treated with
      patupilone.
AB  - BACKGROUND: Only a limited number of cytotoxic drugs have shown activity in
      metastatic colorectal carcinoma. Patupilone is a novel agent with promising
      activity in this common cancer. Diarrhea represents the dose-limiting toxicity of
      patupilone. Measurement of intestinal permeability is one of the potential
      methods of non-invasive laboratory assessment of gastrointestinal toxicity.
      METHODS: We have assessed intestinal permeability by measuring absorption of
      lactulose, mannitol and xylose in 27 previously treated patients with metastatic
      colorectal cancer enrolled in a phase I trial of patupilone. RESULTS:
      Lactulose/mannitol and lactulose/xylose ratios increased after the treatment.
      Significantly higher lactulose/mannitol ratio was observed in patients who had
      severe diarrhea. Moreover, patients who subsequently had an adverse event of
      grade 3 or higher had significantly higher baseline lactulose/mannitol or
      lactulose/xylose ratios. CONCLUSIONS: Measurement of intestinal permeability
      using the lactulose/mannitol test may represent a biomarker for the monitoring,
      or even prediction of toxicity of cytotoxic drugs, including patupilone.

PMID- 24937506
TI  - Biological pathway selection through Bayesian integrative modeling.
AB  - Pathway analysis has become a central approach to understanding the underlying
      biology of differentially expressed genes. As large amounts of microarray data
      have been accumulated in public repositories, flexible methodologies are needed
      to extend the analysis of simple case-control studies in order to place them in
      context with the vast quantities of available and highly heterogeneous data sets.
      To address this challenge, we have developed a two-level model, consisting of 1)
      a joint Bayesian factor model that integrates multiple microarray experiments and
      ties each factor to a predefined pathway and 2) a point mass mixture distribution
      that infers which factors are relevant/irrelevant to each dataset. Our method can
      identify pathways specific to a particular experimental trait which are
      concurrently induced/repressed under a variety of interventions. In this paper,
      we describe the model in depth and provide examples of its utility in simulations
      as well as real data from a study of radiation exposure. Our analysis of the
      radiation study leads to novel insights into the molecular basis of time- and
      dose- dependent response to ionizing radiation in mice peripheral blood. This
      broadly applicable model provides a starting point for generating specific and
      testable hypotheses in a pathway-centric manner.

PMID- 24937508
TI  - Design, fabrication, and characterization of archaeal tetraether free-standing
      planar membranes in a PDMS- and PCB-based fluidic platform.
AB  - The polar lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon
      Sulfolobus acidocaldarius contains exclusively bipolar tetraether lipids, which
      are able to form extraordinarily stable vesicular membranes against a number of
      chemical, physical, and mechanical stressors. PLFE liposomes have thus been
      considered appealing biomaterials holding great promise for biotechnology
      applications such as drug delivery and biosensing. Here we demonstrated that PLFE
      can also form free-standing "planar" membranes on micropores (~100 MUm) of
      polydimethylsiloxane (PDMS) thin films embedded in printed circuit board (PCB)
      based fluidics. To build this device, two novel approaches were employed: (i) an
      S1813 sacrificial layer was used to facilitate the fabrication of the PDMS thin
      film, and (ii) oxygen plasma treatment was utilized to conveniently bond the PDMS
      thin film to the PCB board and the PDMS fluidic chamber. Using electrochemical
      impedance spectroscopy, we found that the dielectric properties of PLFE planar
      membranes suspended on the PDMS films are distinctly different from those
      obtained from diester lipid and triblock copolymer membranes. In addition to
      resistance (R) and capacitance (C) that were commonly seen in all the membranes
      examined, PLFE planar membranes showed an inductance (L) component. Furthermore,
      PLFE planar membranes displayed a relatively large membrane resistance,
      suggesting that, among the membranes examined, PLFE planar membrane would be a
      better matrix for studying channel proteins and transmembrane events. PLFE planar
      membranes also exhibited a sharp decrease in phase angle with the frequency of
      the input AC signal at ~1 MHz, which could be utilized to develop sensors for
      monitoring PLFE membrane integrity in fluidics. Since the stability of free
      standing planar lipid membranes increases with increasing membrane packing
      tightness and PLFE lipid membranes are more tightly packed than those made of
      diester lipids, PLFE free-standing planar membranes are expected to be
      considerably stable. All these salient features make PLFE planar membranes
      particularly attractive for model studies of channel proteins and transmembrane
      events and for high-throughput drug screening and artificial photosynthesis. This
      work can be extended to nanopores of PDMS thin films in microfluidics and
      eventually aid in membrane-based new lab-on-a-chip applications. 

PMID- 24937509
TI  - Powered by DFT: Screening methods that accelerate materials development for
      hydrogen in metals applications.
AB  - CONSPECTUS: Not only is hydrogen critical for current chemical and refining
      processes, it is also projected to be an important energy carrier for future
      green energy systems such as fuel cell vehicles. Scientists have examined light
      metal hydrides for this purpose, which need to have both good thermodynamic
      properties and fast charging/discharging kinetics. The properties of hydrogen in
      metals are also important in the development of membranes for hydrogen
      purification. In this Account, we highlight our recent work aimed at the large
      scale screening of metal-based systems with either favorable hydrogen capacities
      and thermodynamics for hydrogen storage in metal hydrides for use in onboard fuel
      cell vehicles or promising hydrogen permeabilities relative to pure Pd for
      hydrogen separation from high temperature mixed gas streams using dense metal
      membranes. Previously, chemists have found that the metal hydrides need to hit a
      stability sweet spot: if the compound is too stable, it will not release enough
      hydrogen under low temperatures; if the compound is too unstable, the reaction
      may not be reversible under practical conditions. Fortunately, we can use DFT
      based methods to assess this stability via prediction of thermodynamic
      properties, equilibrium reaction pathways, and phase diagrams for candidate metal
      hydride systems with reasonable accuracy using only proposed crystal structures
      and compositions as inputs. We have efficiently screened millions of mixtures of
      pure metals, metal hydrides, and alloys to identify promising reaction schemes
      via the grand canonical linear programming method. Pure Pd and Pd-based membranes
      have ideal hydrogen selectivities over other gases but suffer shortcomings such
      as sensitivity to sulfur poisoning and hydrogen embrittlement. Using a
      combination of detailed DFT, Monte Carlo techniques, and simplified models, we
      are able to accurately predict hydrogen permeabilities of metal membranes and
      screen large libraries of candidate alloys, selections of which are described in
      this Account. To further increase the number of membrane materials that can be
      studied with DFT, computational costs need to be reduced either through methods
      development to break bottlenecks in the performance prediction algorithm,
      particularly related to transition state identification, or through screening
      techniques that take advantage of correlations to bypass constraints.

PMID- 24937507
TI  - Sugar-sweetened beverage intake and cancer recurrence and survival in CALGB 89803
      (Alliance).
AB  - BACKGROUND: In colon cancer patients, obesity, sedentary lifestyle, and high
      dietary glycemic load have been associated with increased risk of cancer
      recurrence. High sugar-sweetened beverage intake has been associated with
      obesity, diabetes, and cardio-metabolic diseases, but the influence on colon
      cancer survival is unknown. METHODS: We assessed the association between sugar
      sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage
      III colon cancer patients who completed food frequency questionnaires as part of
      a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard
      ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox
      proportional hazard models. RESULTS: Patients consuming >= 2 servings of sugar
      sweetened beverages per day experienced an adjusted HR for disease recurrence or
      mortality of 1.67 (95% CI, 1.04-2.68), compared with those consuming <2 servings
      per month (P(trend) = 0.02). The association of sugar-sweetened beverages on
      cancer recurrence or mortality appeared greater among patients who were both
      overweight (body mass index >= 2 5 kg/m(2)) and less physically active (metabolic
      equivalent task-hours per week <18) (HR = 2.22; 95% CI, 1.29-3.81, P(trend) =
      0.0025). CONCLUSION: Higher sugar-sweetened beverage intake was associated with a
      significantly increased risk of cancer recurrence and mortality in stage III
      colon cancer patients.

PMID- 24937510
TI  - Impact of an academic-community partnership in medical education on community
      health: evaluation of a novel student-based home visitation program.
AB  - OBJECTIVES: Current US healthcare delivery systems do not adequately address
      healthcare demands. Physicians are integral but rarely emphasize prevention as a
      primary tool to change health outcomes. Home visitation is an effective method
      for changing health outcomes in some populations. The Florida International
      University Herbert Wertheim College of Medicine Green Family Foundation
      NeighborhoodHELP service-learning program assigns medical students to be members
      of interprofessional teams that conduct household visits to determine their
      healthcare needs. METHODS: We performed a prospective evaluation of 330
      households randomly assigned to one of two groups: visitation from a student team
      (intervention group) or limited intervention (control group). The program design
      allowed randomly selected control households to replace intervention-group
      households that left the program of their own volition. All of the households
      were surveyed at baseline and after 1 year of participation in the study.
      RESULTS: After 1 year in the program and after adjustment for confounders,
      intervention group households proved more likely (P <= 0.05) than control
      households to have undergone physical examinations, blood pressure monitoring,
      and cervical cytology screenings. Cholesterol screenings and mammograms were
      borderline significant (P = 0.05 and P = 0.06, respectively). CONCLUSIONS: This
      study supports the value of home visitation by interprofessional student teams as
      an effective way to increase the use of preventive health measures. The study
      underscores the important role interprofessional student teams may play in
      improving the health of US communities, while students concurrently learn about
      primary prevention and primary care.

PMID- 24937511
TI  - Commentary on "Impact of an academic-community partnership in medical education
      on community health: evaluation of a novel student-based home visitation
      program".

PMID- 24937513
TI  - Commentary on "Surge in US outpatient vitamin D deficiency diagnoses: National
      Ambulatory Medical Care Survey analysis".

PMID- 24937512
TI  - Surge in US outpatient vitamin D deficiency diagnoses: National Ambulatory
      Medical Care Survey analysis.
AB  - OBJECTIVES: In light of the growing medical interest in the potential
      consequences of vitamin D deficiency, it is important that clinicians are
      informed about the varying factors that may complicate the assessment of vitamin
      D status and the diagnosis of deficiency. To better understand the frequency of
      vitamin D deficiency diagnoses in the ambulatory setting over time, the objective
      of this investigation was to examine unspecific, general, and bone-related
      vitamin D deficiency diagnoses between 2007 and 2010 and to determine whether the
      rate of diagnoses differed by patient age and sex. METHODS: We used data from the
      National Ambulatory Medical Care Survey and the National Hospital Ambulatory
      Medical Care Survey to assess the rate of vitamin D deficiency diagnoses provided
      between 2007 and 2010 during outpatient visits with nonfederally employed
      physicians in offices and hospitals. Two hundred ninety-two unweighted patient
      visit records were included. Trends in vitamin D deficiency diagnosis over time,
      diagnosis of bone disease associated with a vitamin D deficiency diagnosis, and
      patient age and sex were reported. RESULTS: The number of diagnoses for vitamin D
      deficiency rapidly increased from 2007 to 2010. More than 97% of diagnoses were
      for unspecific vitamin D deficiency; 9.6% of vitamin D deficiency visits also
      resulted in a diagnosis of osteoporosis or bone fracture. CONCLUSIONS: Although
      the rate of diagnoses for vitamin D deficiency increased between 2007 and 2010,
      many diagnoses rendered were for nonspecific disease; therefore, vitamin D
      deficiency screening may have been ordered for preventive care purposes rather
      than as a diagnostic aid.

PMID- 24937515
TI  - Missed esophageal and gastric cancers after esophagogastroduodenoscopy in a
      midwestern military veteran population.
AB  - OBJECTIVES: Esophagogastroduodenoscopy (EGD) with biopsy has become the standard
      procedure for diagnosing esophageal and gastric cancers (EGC) and is considered
      to have high sensitivity and specificity. To date, few studies have attempted to
      examine the rates of missed EGC after EGD and no study addresses the rate of
      missed EGC in a military veteran patient population. This led to us examine
      missed EGCs at our VA Medical Center across a 10-year period. METHODS: An
      electronic database was used to identify patients who were diagnosed between 2000
      and 2010 as having EGC. Missed cancers were defined as cancers diagnosed within 1
      year of EGD, possible missed cancers as those diagnosed 1 to 3 years after EGD,
      and latent cancers as those diagnosed between 3 and 5 years after EGD. RESULTS: A
      total of 94 patients fulfilled the study criteria: 69 had esophageal cancer and
      25 had gastric cancer diagnosed at our institution during the study period. Of
      the included cases, one patient had a missed cancer (1.06%) and four patients had
      possible missed cancers (4.26%); no patients had latent cancer. CONCLUSIONS: The
      true incidence of missed EGC in military veteran patients is not known. It is
      difficult to compare our findings to those of other studies because of the
      heterogeneity of studies. Our study echoes the findings of the others: EGD
      remains an important and effective tool in diagnosing EGC. At the same time, it
      also points out an important limitation, that EGC can be missed on EGD. Our
      findings also emphasize the importance of obtaining biopsies of any abnormality
      and timely clinical follow-up and by repeat EGD as needed.

PMID- 24937514
TI  - Risk factors for inadequate colonoscopy bowel preparations in African Americans
      and whites at an urban medical center.
AB  - OBJECTIVES: Poor bowel preparation leads to inadequate examinations and shorter
      surveillance intervals for colorectal cancer screening. Previous studies
      regarding risk factors for inadequate preparation have not included large numbers
      of African Americans. Our aim was to determine the prevalence of inadequate bowel
      preparation on initial and follow-up colonoscopy in a large, racially diverse
      patient population. METHODS: Colonoscopies performed during a 1-year period were
      analyzed retrospectively. Factors including age, sex, race, and start time were
      recorded. Patient ZIP codes were linked to census data to estimate education and
      income. For examinations with inadequate bowel preparations, we collected data on
      recommendations and the preparation quality of follow-up procedures. RESULTS: We
      included 3741 patients (40.2% African American). Of these, 66.9% had adequate
      bowel preparation and 33.1% had inadequate bowel preparation. African Americans
      had the highest prevalence of inadequate preparations at 43.0%. African American
      race was a predictor of inadequate bowel preparation, despite controlling for
      education and income. Age, male sex, and procedure taking place after 12 pm also
      were risk factors for inadequate preparation. Receipt of specific preparation
      instructions on the endoscopy report did not affect preparation quality on follow
      up examination. Our study found a high rate (33.1%) of inadequate bowel
      preparations, and African American race was found to be an independent risk
      factor for inadequate preparation. We validated previously reported risk factors
      including age, male sex, and later procedure time. Finally, we noted high rates
      of inadequate preparation on follow-up examinations. CONCLUSIONS: Improving the
      quality of colonoscopy bowel preparation is important for colorectal cancer
      prevention, especially in high-risk populations such as African Americans.

PMID- 24937516
TI  - Gastrointestinal cancers in Mississippi.
AB  - OBJECTIVES: According to a 2007 US Census Bureau report, Mississippi is the
      poorest state in the United States and is ranked last among all 50 states for
      overall quality of health. The objective of the study was to describe
      gastrointestinal (GI) cancers in Mississippi overall and the Mississippi Delta
      region in particular. METHODS: The age-adjusted incidence rates for GI cancers
      for 2003-2007, compiled from the Mississippi Cancer Registry and the Centers for
      Disease Control and Prevention's National Program of Cancer Registries, were
      retrieved and compared among 18 Mississippi Delta counties, 64 non-Delta
      counties, the entire state of Mississippi, and the United States. Colorectal
      cancer incidence rates and national rankings were correlated with influencing
      factors of race, obesity, diabetes mellitus, education, unemployment rate,
      availability of health insurance and primary care physicians, physical activity,
      diet, and per capita income. RESULTS: Compared with the United States as a whole,
      Mississippi had higher rates of colon and rectal cancers and a lower overall rate
      of gallbladder cancers in both whites and African Americans. Of all GI cancers,
      only liver, intrahepatic bile duct, and gallbladder cancers had lower age
      adjusted incidence rates in the Mississippi Delta region. There was a large
      difference between African Americans and whites in the Delta region. Whites
      residing in the Delta counties had higher incidence rates than African Americans
      of all cancers except liver and intrahepatic bile duct cancers. CONCLUSIONS: The
      majority of GI cancers had higher incidence rates in the Mississippi Delta than
      non-Delta counties and in the entire state than the United States. These
      disparities observed on a regional and ethnic basis call for targeted prevention
      efforts to eliminate disparities in GI cancer incidence rates.

PMID- 24937517
TI  - Hyperuricemia, gout, and related comorbidities: cause and effect on a two-way
      street.
AB  - The prevalence of gout and hyperuricemia has increased dramatically during the
      last several decades, to the point that gout is the most common inflammatory
      arthritis in the United States, affecting approximately 8 million Americans.
      Patients with gout frequently have multiple comorbidities, including
      hypertension, chronic kidney disease, cardiovascular disease, obesity, diabetes,
      and hyperlipidemia, all of which have significant adverse impact on public
      health. In some cases (eg, chronic kidney disease) it is clear that the presence
      of the comorbidity contributes to the progression of hyperuricemia and/or gout.
      Conversely, the question of whether gout/hyperuricemia themselves contribute to
      the pathogenesis of gout comorbidities is an area of intensifying investigation.
      In vitro and animal models, large epidemiologic studies, and small clinical
      trials suggest that gout and/or hyperuricemia may contribute to hypertension,
      chronic kidney disease, and cardiovascular disease. More limited hypothesis
      generating studies suggest a potential role for diabetes and obesity. Given that
      available drugs can lower serum urate levels and manage gout, it would be
      important to know whether not only gout and/or hyperuricemia can contribute to
      comorbidities but also better gout/hyperuricemic control can ameliorate some or
      all of these related conditions. We review the clinical associations between gout
      and its common comorbid conditions and the evidence supporting a causal relation
      between them. The evidence that gout and hyperuricemia contribute to the
      pathogenesis of their comorbidities creates greater urgency for appropriate gout
      management. 

PMID- 24937518
TI  - Advanced, neglected basal cell carcinoma.
AB  - Although basal cell carcinoma (BCC) rarely metastasizes and has a cure rate >95%
      when diagnosed early in its course, BCC causes significant morbidity and presents
      an enormous burden to the healthcare system worldwide. Patients who present late
      in the course of their disease are particularly challenging in that their
      treatment can be more complicated and less likely to be effective than had they
      presented earlier. Given the high prevalence of this malignancy and the morbidity
      associated with a late presentation, healthcare professionals should be familiar
      with the consequences of neglected BCCs, as well as their management after
      presentation. Knowledge of patient risk characteristics may allow earlier
      engagement and diagnosis of patients, before more significant morbidity occurs. 

PMID- 24937519
TI  - Commentary on "Advanced, neglected basal cell carcinoma".

PMID- 24937520
TI  - Serum biomarkers for traumatic brain injury.
AB  - There is a lack of reliable serum biomarkers for routine use in the diagnostic
      workup of people with traumatic brain injury. Multiple biomediators and
      biomarkers have been described in the pertinent literature in recent years;
      however, only a few candidate molecules have been associated with high
      sensitivity and high specificity for risk stratification and outcome prediction
      after traumatic brain injury. This review was designed to provide an overview of
      the state of the art regarding established serum biomarkers in the field and to
      outline future directions of investigation. 

PMID- 24937521
TI  - Investigational biomarkers for pancreatic adenocarcinoma: where do we stand?
AB  - Although the outcomes for pancreatic ductal adenocarcinoma (PDAC) remain
      disappointing, there has been considerable improvement in the 5-year survival
      rate of patients with resectable disease. As such, an R0 surgical resection
      (microscopic tumor clearance) offers patients with PDAC the greatest survival
      benefit. Carbohydrate antigen 19-9, the only US Food and Drug Administration
      approved biomarker for PDAC, is a poor screening tool and is most informative
      after PDAC resection. Consequently, there has been a tremendous initiative to
      discover novel biomarkers that may aid in detecting the disease earlier,
      improving prognosis, and predicting response to available chemotherapy. The
      number of implicated biomarkers in PDAC is indeed staggering, with >2500 proposed
      candidates presented in the recent literature. A vast majority of these
      biomarkers, however, remain in the investigational phase. This review categorizes
      the most promising biomarkers--those closest to potential clinical application-
      into diagnostic and prognostic/predictive groups. The greatest challenge likely
      lies in the search for an effective diagnostic biomarker that can accurately
      discriminate between malignant and benign disease, and thereby facilitate earlier
      identification of those patients with PDAC who may benefit most from surgical
      resection.

PMID- 24937522
TI  - Commentary on "Investigational biomarkers for pancreatic adenocarcinoma: where do
      we stand?".

PMID- 24937523
TI  - Canine-assisted therapy in the inpatient setting.
AB  - Canine-assisted therapy (CAT) is widely used in outpatient settings, yet there is
      little published literature regarding its use, efficacy, and safety in the
      inpatient setting. The primary objective of this review was to consolidate
      published information regarding CAT efficacy and safety in the inpatient
      population. The secondary objective was to review safety concerns associated with
      CAT. The databases PubMed, Ovid MEDLINE, and Web of Knowledge were searched using
      the dates April 2003-April 2013 with the terms "animal assisted therapy" and "pet
      therapy." Articles were reviewed for the relevance of CAT in the inpatient
      setting, and those meeting our criteria were included in the study. The
      references of selected articles also were reviewed and included if study criteria
      were met. The review of the literature resulted in 429 total articles using the
      search terms. Of the 429 articles, 177 were duplicates and 218 pertained to the
      outpatient setting or involved animal therapies other than canine, leaving 34
      articles that met the search criteria. The bibliography review of the 34 articles
      yielded an additional 10 articles. Our review of the literature showed that in
      the inpatient setting, CAT is an effective therapy among patients of all ages and
      with various medical problems and is safe, with no transmitted infections
      reported. 

PMID- 24937524
TI  - Commentary on "Canine-assisted therapy in the inpatient setting".

PMID- 24937526
TI  - Design and synthesis of hydrolytically stable multivalent ligands bearing
      thiodigalactoside analogues for peanut lectin and human galectin-3 binding.
AB  - Herein, we describe the design and synthesis of a novel family of hydrolytically
      stable glycoclusters bearing thiodigalactoside (TDG) analogues as recognition
      elements of beta-galactoside binding lectins. The TDG analogue was synthesized by
      thioglycosylation of a 6-S-acetyl-alpha-D-glucosyl bromide with the
      isothiouronium salt of 2,3,4,6-tetra-O-acetyl-beta-D-galactose. Further
      propargylation of the TDG analogue allowed the coupling to azido-functionalized
      oligosaccharide scaffolds through copper(I)-catalyzed azide-alkyne cycloaddition
      (CuAAC) under microwave activation. The final mono-, di-, and tetravalent ligands
      were resistant to enzymatic hydrolisis by Escherichia coli beta-galactosidase.
      Binding affinities to peanut agglutinin and human galectin-3 were measured by
      isothermal titration calorimetry which showed K(a) constants in the micromolar
      range as well as a multivalent effect. Monovalent ligand exhibited a binding
      affinity higher than that of thiodigalactoside. Docking studies performed with a
      model ligand on both beta-galactoside binding lectins showed additional
      interactions between the triazole ring and lectin amino acid residues, suggesting
      a positive effect of this aromatic residue on the biological activity.

PMID- 24937527
TI  - The deployment of carbon monoxide wireless sensor network (CO-WSN) for ambient
      air monitoring.
AB  - Wireless sensor networks are becoming increasingly important as an alternative
      solution for environment monitoring because they can reduce cost and complexity.
      Also, they can improve reliability and data availability in places where
      traditional monitoring methods are difficult to site. In this study, a carbon
      monoxide wireless sensor network (CO-WSN) was developed to measure carbon
      monoxide concentrations at a major traffic intersection near the University of
      Cincinnati main campus. The system has been deployed over two weeks during Fall
      2010, and Summer 2011-2012, traffic data was also recorded by using a manual
      traffic counter and a video camcorder to characterize vehicles at the
      intersection 24 h, particularly, during the morning and evening peak hour
      periods. According to the field test results, the 1 hr-average CO concentrations
      were found to range from 0.1-1.0 ppm which is lower than the National Ambient Air
      Quality Standards (NAAQS) 35 ppm on a one-hour averaging period. During rush hour
      periods, the traffic volume at the intersection varied from 2,067 to 3,076
      vehicles per hour with 97% being passenger vehicles. Furthermore, the traffic
      volume based on a 1-h average showed good correlation (R2 = 0.87) with the 1-h
      average CO-WSN concentrations for morning and evening peak time periods whereas
      CO-WSN results provided a moderate correlation (R2 = 0.42) with 24 hours traffic
      volume due to fluctuated changes of meteorological conditions. It is concluded
      that the performance and the reliability of wireless ambient air monitoring
      networks can be used as an alternative method for real time air monitoring. 

PMID- 24937528
TI  - Protecting health from climate change in the WHO European Region.
AB  - "How far are we in implementing climate change and health action in the WHO
      European Region?" This was the question addressed to representatives of WHO
      European Member States of the working group on health in climate change (HIC).
      Twenty-two Member States provided answers to a comprehensive questionnaire that
      focused around eight thematic areas (Governance; Vulnerability, impact and
      adaptation (health) assessments; Adaptation strategies and action plans; Climate
      change mitigation; Strengthening health systems; Raising awareness and building
      capacity; Greening health services; and Sharing best practices). Strong areas of
      development are climate change vulnerability and impact assessments, as well as
      strengthening health systems and awareness raising. Areas where implementation
      would benefit from further action are the development of National Health
      Adaptation Plans, greening health systems, sharing best practice and reducing
      greenhouse gas emissions in other sectors. At the Parma Conference in 2010, the
      European Ministerial Commitment to Act on climate change and health and the
      European Regional Framework for Action to protect health from climate change were
      endorsed by fifty three European Member States. The results of this questionnaire
      are the most comprehensive assessment so far of the progress made by WHO European
      Member States to protecting public health from climate change since the
      agreements in Parma and the World Health Assembly Resolution in 2008. 

PMID- 24937529
TI  - Microbial community structures and dynamics in the O3/BAC drinking water
      treatment process.
AB  - Effectiveness of drinking water treatment, in particular pathogen control during
      the water treatment process, is always a major public health concern. In this
      investigation, the application of PCR-DGGE technology to the analysis of
      microbial community structures and dynamics in the drinking water treatment
      process revealed several dominant microbial populations including: alpha
      Proteobacteria, beta-Proteobacteria, gamma-Proteobacteria, Bacteroidetes,
      Actinobacteria Firmicutes and Cyanobacteria. alpha-Proteobacteria and beta
      Proteobacteria were the dominant bacteria during the whole process. Bacteroidetes
      and Firmicutes were the dominant bacteria before and after treatment,
      respectively. Firmicutes showed season-dependent changes in population dynamics.
      Importantly, gamma-Proteobacteria, which is a class of medically important
      bacteria, was well controlled by the O3/biological activated carbon (BAC)
      treatment, resulting in improved effluent water bio-safety. 

PMID- 24937530
TI  - Evaluating determinants of environmental risk perception for risk management in
      contaminated sites.
AB  - Understanding the differences in the risk judgments of residents of industrial
      communities potentially provides insights into how to develop appropriate risk
      communication strategies. This study aimed to explore citizens' fundamental
      understanding of risk-related judgments and to identify the factors contributing
      to perceived risks. An exploratory model was created to investigate the public's
      risk judgments. In this model, the relationship between laypeople's perceived
      risks and the factors related to the physical nature of risks (such as perceived
      probability of environmental contamination, probability of receiving impacts, and
      severity of catastrophic consequences) were examined by means of multiple
      regression analysis. Psychological factors, such as the ability to control the
      risks, concerns, experiences, and perceived benefits of industrial development
      were also included in the analysis. The Maptaphut industrial area in Rayong
      Province, Thailand was selected as a case study. A survey of 181 residents of
      communities experiencing different levels of hazardous gas contamination revealed
      rational risk judgments by inhabitants of high-risk and moderate-risk
      communities, based on their perceived probability of contamination, probability
      of receiving impacts, and perceived catastrophic consequences. However, risks
      assessed by people in low-risk communities could not be rationally explained and
      were influenced by their collective experiences. 

PMID- 24937531
TI  - Plasma exosome microRNA profiling unravels a new potential modulator of
      adiponectin pathway in diabetes: effect of glycemic control.
AB  - CONTEXT: Type 2 diabetes is a chronic disease characterized by inadequate beta
      cell response to the progressive insulin resistance. MicroRNAs (miRNAs) are
      short, endogenous, noncoding RNAs representing a class of powerful gene
      expression modulators. Previous population studies observed a modulation of
      circulating miRNAs in diabetic patients; however, few data are presently
      available on miRNA modulation in diabetic patients naive to pharmacological
      treatment as well as the effect of glycemic control on this. OBJECTIVE: We aimed
      at studying circulating miRNA expression in diabetic patients naive to treatment
      and at investigating the influence on this of glycemic control. DESIGN: This was
      a case-control study. PARTICIPANTS: Eighteen treatment-naive diabetic patients
      with poor metabolic control and 12 control patients participated in the study.
      MAIN OUTCOME MEASURES: Wide miRNA expression profiling was performed, and the
      expression of miRNAs found to be dysregulated was then validated by quantitative
      RT-PCR. Finally, algorithm-identified putative miRNA targets were evaluated by
      quantitative RT-PCR and ELISA. RESULTS: In diabetic patients, microarray analysis
      showed that four miRNAs are increased, whereas 21 miRNAs are decreased.
      Quantitative RT-PCR validation confirmed the significant up-regulation of miR-326
      (P = .004) and down-regulation of let-7a (P < .001) and let-7f (P = .003).
      Notably, an inverse negative correlation was found between circulating miR-326
      and its putative target adiponectin (p = -0.479, P = .009). After 12 months of
      antidiabetic treatment, quantitative RT-PCR data analysis showed that miR-326
      levels were unaffected, whereas the levels of let-7a and let-7f were
      significantly increased. CONCLUSIONS: Treatment-naive, poorly controlled diabetic
      patients show a significant dysregulation of miRNAs involved in the regulation of
      the adiponectin pathway, a phenomenon that may be reversed, at least in part, by
      improved glycemic control.

PMID- 24937532
TI  - Diabetes-associated microRNAs in pediatric patients with type 1 diabetes
      mellitus: a cross-sectional cohort study.
AB  - CONTEXT: Circulating microRNAs (miRNAs/miRs) are used as novel biomarkers for
      diseases. miR-21, miR-126, and miR-210 are known to be deregulated in vivo or in
      vitro under diabetic conditions. OBJECTIVE: The aim of this study was to
      investigate the circulating miR-21, miR-126, and miR-210 in plasma and urine from
      pediatric patients with type 1 diabetes and to link our findings to
      cardiovascular and diabetic nephropathy risk factors in children with type 1
      diabetes. DESIGN: miR-21, miR-126, and miR-210 concentrations were measured with
      quantitative RT-PCR in plasma and urine samples from 68 pediatric patients with
      type 1 diabetes and 79 sex- and age-matched controls. SETTING: The study
      consisted of clinical pediatric patients with type 1 diabetes. PATIENTS OR OTHER
      PARTICIPANTS: Inclusion criterion for patients was diagnosed type 1 diabetes.
      Exclusion criteria were febrile illness during the last 3 months; chronic
      inflammatory or rheumatic disease; hepatitis; HIV; glucocorticoid treatment;
      liver, renal, or cardiac failure; or hereditary dyslipidemia. Patients were age
      and sex matched to controls. MAIN OUTCOME MEASURE(S): Main outcome parameters
      were changes in miR-21, miR-126, and miR-210 concentration in plasma and urine
      from type 1 diabetic patients compared with corresponding controls. RESULTS:
      Circulating miRNA levels of miR-21 and miR-210 were significantly up-regulated in
      the plasma and urine of the type 1 diabetic patients. Urinary miR-126 levels in
      diabetic patients were significantly lower than in age- and gender-matched
      controls and negatively correlated between the patient's glycated hemoglobin mean
      and miR-126 concentration value. In contrast, circulating miR-126 levels in
      plasma were comparable in both cohorts. For urinary miR-21, we found by an
      adjusted receiver-operating characteristic-curve analysis with an area under the
      curve of 0.78. CONCLUSIONS: Type 1 diabetic pediatric patients revealed a
      significant deregulation of miR-21, miR-126, and miR-210 in plasma and urinary
      samples, which might indicate an early onset of diabetic-associated diseases.

PMID- 24937533
TI  - Significance of serum magnesium as an independent correlative factor on the
      parathyroid hormone level in uremic patients.
AB  - CONTEXT: PTH is a critical factor in mineral homeostasis, and chronic kidney
      disease mineral and bone metabolism disorder is a very important problem in
      patients with renal failure. Abnormal levels of PTH, serum phosphate, and calcium
      influence chronic kidney disease mineral and bone metabolism disorder, but there
      is little information about the influence of magnesium (Mg) on PTH. OBJECTIVE:
      The aim of this study was to elucidate the correlation between magnesium and PTH
      levels in uremic patients just prior to beginning hemodialysis (HD) for the first
      time. PATIENTS: We enrolled 1231 patients in nine Japanese facilities who had
      begun HD for end-stage renal disease. We investigated their serum Mg levels and
      the correlation between intact PTH (iPTH) and the serum Mg levels and other
      clinical parameters and medications. RESULTS: The mean serum Mg was 2.2 +/- 0.5
      mg/dL, and hypermagnesemia was found in 663 patients (53.9%). Divided into two
      groups according to median iPTH level, the serum Mg levels were significantly
      higher in patients with low iPTH (2.3 +/- 0.5 vs 2.1 +/- 0.5, P < .01).
      Furthermore, divided into two groups according to the Mg level, iPTH levels were
      lower in patients with high Mg than in patients with normal serum Mg levels
      (277.9 +/- 195.9 pg/mL vs 321.9 +/- 203.7 pg/mL, P < .01). In the multiple
      regression analysis according to the effect of iPTH level, the serum Mg level was
      an independent variable after adjustment for other factors. CONCLUSIONS: A high
      serum level of Mg is frequent in uremic patients with end-stage renal disease
      just prior to beginning HD. In the present set of patients, there was a
      significant correlation between the serum Mg and iPTH levels. Furthermore, the
      serum Mg level was an independent factor apart from the other factors regulating
      iPTH. These results suggest that serum Mg may be one of the factors regulating
      the serum PTH level in uremic patients.

PMID- 24937534
TI  - Hypoxemia and glycemic control in type 2 diabetes mellitus with extreme obesity.
AB  - CONTEXT: Obstructive sleep apnea (OSA) has been shown to be associated with type
      2 diabetes mellitus (DM). Studies on healthy individuals found that OSA is
      associated with lower insulin sensitivity. We hypothesized that nocturnal
      hypoxemia from OSA is associated with poorer glycemia in severely obese DM
      individuals. DESIGN AND SETTING: This was a retrospective observational study of
      122 non-DM, 126 non-insulin-treated DM, and 35 insulin-treated DM patients. Data
      were collected on demographic characteristics, body mass index, and
      comorbidities. An overnight sleep study was performed in all patients, and OSA
      was defined as an apnea-hypopnea index of >=5 events/h. RESULTS: There were more
      males (P = .003) and a lower proportion of white Europeans (P = .010) among DM
      patients. The prevalence of OSA was 80.1% in DM and 63.1% in non-DM individuals
      (P = .001). DM individuals also had lower oxygen saturation (O2) (P = .0106),
      greater percentage of time spent under 90% oxygen saturation (%TST<90%) (P =
      .0067), and higher apnea-hypopnea index (P = .0085). Regression analysis showed
      that %TST<90% and minimum O2 saturations were associated with worse hemoglobin
      A1c results among DM individuals. Every 10% reduction in minimum O2 was
      associated with a 0.3% increase in HbA1c, whereas a 10% increase in %TST<90% was
      associated with a 0.2% increase in hemoglobin A1c after adjusting for a range of
      potential confounders. CONCLUSION: The high OSA prevalence in DM individuals and
      a positive relationship between nocturnal hypoxemia and glycemia supports the
      need to assess correction of hypoxemia as a management strategy for glycemic
      control.

PMID- 24937535
TI  - The disposition index does not reflect beta-cell function in IGT subjects treated
      with pioglitazone.
AB  - AIMS AND HYPOTHESIS: The insulin secretion/insulin resistance (IR) (disposition)
      index (DeltaI/DeltaG / IR, where Delta is change from baseline, I is insulin, and
      G is glucose) is commonly used as a measure of beta-cell function. This
      relationship is curvilinear and becomes linear when log transformed. DeltaI is
      determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance
      of insulin. We postulated that the characteristic curvilinear relationship would
      be lost if Delta plasma C-peptide (DeltaCP) (instead of Delta plasma insulin) was
      plotted against insulin sensitivity. METHODS: A total of 441 individuals with
      impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance
      test and were randomized to pioglitazone or placebo for 2.4 years. RESULTS:
      Pioglitazone reduced IGT conversion to diabetes by 72% (P < .0001). DeltaI/DeltaG
      vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear
      relationship. However, when DeltaCP/DeltaG or DeltaISR/DeltaG was plotted against
      the Matsuda index, the curvilinear relationship was completely lost. This
      discordance was explained by 2 distinct physiologic effects that altered plasma
      insulin response in opposite directions: 1) increased ISR and 2) augmented
      metabolic clearance of insulin. The net result was a decline in the plasma
      insulin response to hyperglycemia during the oral glucose tolerance test. These
      findings demonstrate a physiologic control mechanism wherein the increase in ISR
      ensures adequate insulin delivery into the portal circulation to suppress hepatic
      glucose production while delivering a reduced but sufficient amount of insulin to
      peripheral tissues to maintain the pioglitazone-mediated improvement in insulin
      sensitivity without excessive hyperinsulinemia. CONCLUSIONS: These results
      demonstrate the validity of the disposition index when relating the plasma
      insulin response to insulin sensitivity but underscore the pitfall of this index
      when drawing conclusions about beta-cell function, because insulin secretion
      declined despite an increase in the plasma insulin response.

PMID- 24937536
TI  - Adipose tissue and metabolic alterations: regional differences in fat cell size
      and number matter, but differently: a cross-sectional study.
AB  - OBJECTIVE: White adipose tissue can expand by increasing the size and/or number
      of fat cells. Although increased sc and visceral fat cell size associates with an
      adverse metabolic profile, the relationship with fat cell number in either depot
      is unknown. We hypothesized that adipocyte number and size displayed different
      relationships with clinically relevant metabolic variables. METHODS: This was a
      cross-sectional study of 204 patients scheduled for gastric bypass surgery. Fat
      cell size and number were determined in visceral and abdominal sc adipose tissue
      and related to insulin sensitivity (by hyperinsulinemic euglycemic clamp),
      fasting plasma levels of insulin, triglycerides and high-density lipoprotein
      (HDL) cholesterol. RESULTS: Visceral and sc fat cell volumes were positively
      correlated with insulin and triglyceride levels and negatively with insulin
      sensitivity and HDL-cholesterol (P = .0020 or better). In contrast, although
      visceral fat cell number did not associate with any metabolic parameter, sc
      adipocyte number displayed a positive association with insulin sensitivity and
      HDL-cholesterol and a negative relationship with insulin and triglyceride levels
      (P = .0014 or better). All results were independent of body fat mass.
      CONCLUSIONS: Variations in fat cell size and number correlate differently with
      metabolic parameters in obesity. Increased fat cell size in visceral and sc
      depots associates with a pernicious metabolic profile, whereas increased sc, but
      not visceral, fat cell number correlates with a more beneficial phenotype.
      Whether determination of sc fat cell number, in addition to adipocyte size, may
      have a predictive value for the risk of type 2 diabetes needs to be demonstrated
      in prospective or mechanistic studies.

PMID- 24937537
TI  - Testicular synthesis and vitamin D action.
AB  - CONTEXT: The vitamin D system has pleiotropic effects not only in bone
      metabolism. Its role in testicular steroidogenesis is new and deserves intensive
      research. OBJECTIVE: We hypothesize that vitamin D, especially 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3 (calcitriol)] induces male steroidogenesis and
      intend to identify its impact on genes and pathways in testicular androgen
      regulation. METHODS: Human adult primary testicular cells were isolated, treated
      with 1,25(OH)2D3, and their gene expression levels profiled by microarray
      analysis. Highly regulated genes were confirmed by real-time quantitative PCR. In
      addition, the effects of 1,25(OH)2D3 in combination with LH and IGF-I on the gene
      expression level of androgens were assessed. T levels in the culture media were
      determined by a high-resolution ELISA. The expression of vitamin D receptor was
      confirmed at baseline and after 1,25(OH)2D3 stimulation using
      immunocytochemistry. RESULTS: Microarrays depicted 63 genes significantly
      regulated by 1,25(OH)2D3, including genes related to male androgen and vitamin D
      metabolism, mainly triggered by the vitamin D receptor/retinoid X receptor
      activation. 1,25(OH)2D3 led to significant changes in the expression profiles of
      reproductive genes and significantly increased T synthesis in human testicular
      cell cultures. CONCLUSIONS: Data from our human primary testicular cell culture
      model suggest that vitamin D plays a major role in male steroidogenesis in vitro.

PMID- 24937538
TI  - Involvement of PIT-1-reactive cytotoxic T lymphocytes in anti-PIT-1 antibody
      syndrome.
AB  - CONTEXT: Anti-pituitary-specific transcriptional factor 1 (PIT-1) antibody
      syndrome is characterized by acquired growth hormone (GH), prolactin (PRL), and
      thyroid-stimulating hormone (TSH) deficiencies associated with circulating anti
      PIT-1 antibodies. Although autoimmunity to PIT-1 has been suggested as a
      pathogenesis, the precise mechanism of the syndrome remains unclarified.
      OBJECTIVE: To elucidate the involvement of antibody- or cell-mediated immunity in
      anti-PIT-1 antibody syndrome. MATERIALS AND METHODS: To investigate a direct
      effect of anti-PIT-1 antibody on pituitary cells, cell proliferation, and
      cytotoxicity detection assays were performed using patient serum. Enzyme-linked
      immunospot (ELISpot) assay was performed to evaluate the involvement of PIT-1
      reactive cytotoxic T lymphocytes (CTLs). An immunohistochemical analysis using
      anti-CD4 or anti-CD8 antibody was performed to examine tissue infiltration by
      CTLs. RESULTS: Patient serum did not exhibit any inhibitory effect on cell
      proliferation and secretion of GH and PRL in GH3 cells. In addition, complement
      dependent cytotoxicity was not detected in patient serum on GH3 cells or primary
      pituitary cells. The ELISpot assay revealed the presence of CTLs that
      specifically reacted to the recombinant PIT-1 protein in the patient's peripheral
      lymphocytes. CD8(+) cell infiltrations, which is the characteristic of CTLs, were
      observed in the pituitary gland, adrenal gland, stomach, thyroid gland, liver,
      and pancreas of the patient with anti-PIT-1 antibody syndrome. CONCLUSIONS: These
      results suggest that the anti-PIT-1 antibody is not a cause but a marker of anti
      PIT-1 antibody syndrome, in which CTLs play a pivotal role in the pathogenesis.

PMID- 24937539
TI  - Long-term follow-up of children with congenital hyperinsulinism on octreotide
      therapy.
AB  - CONTEXT: Octreotide, a somatostatin analog, is commonly used in diazoxide
      unresponsive congenital hyperinsulinism (CHI) patients as a second-line therapy.
      OBJECTIVE: The aims of this study were to evaluate the dose range, side effects,
      and long-term follow-up of octreotide therapy in a large cohort of CHI patients.
      SETTING: The study was conducted at an international referral center for the
      management of CHI. PATIENTS: Twenty-eight (17 males) diazoxide unresponsive CHI
      patients (15 biallelic and 10 monoallelic ATP sensitive potassium channel
      mutation) managed with daily multidose octreotide therapy between 2001 and 2013
      participated in the study. MAIN OUTCOME MEASURES: Regular follow-up of auxology,
      growth factors (serum IGF-1 and IGF binding protein 3 levels), thyroid functions,
      liver function tests, and hepatobiliary ultrasonography were measured. RESULTS:
      The median age of CHI diagnosis was 1 week (range 1-80 wk). The mean (+/-SD) dose
      of octreotide required was 17.8 (+/-7.5) MUg/kg . d (range 7.5-30 MUg/kg . d).
      The mean (+/-SD) duration of follow-up on octreotide therapy was 52.4 (+/-33.8)
      months (range 6 mo to 9.5 y). Elevation of liver enzymes was the most prevalent
      side effect (n = 13; 46.4%), which resolved spontaneously. Gallbladder pathology
      was detected in nine patients (32%). Mean (+/-SD) duration of octreotide therapy
      before the development of gallbladder pathology was 4.3 (+/-4.6 mo), whereas 19
      patients were free of gallstones after a follow-up of 53.6 +/- 32.9 months on
      octreotide therapy. There was no relationship between the dose or the duration of
      octreotide therapy and development of gallbladder pathology or liver dysfunction.
      CONCLUSIONS: Transient elevation of liver enzymes and asymptomatic gallbladder
      pathology were the most prevalent long-term side effects of octreotide therapy.
      There was no correlation between the dose or the duration of octreotide therapy
      and development of liver dysfunction and gallbladder pathology.

PMID- 24937540
TI  - Association between expression of FABPpm in skeletal muscle and insulin
      sensitivity in intramyocellular lipid-accumulated nonobese men.
AB  - CONTEXT: Intramyocellular lipid (IMCL) accumulation is observed in both insulin
      resistant subjects and insulin-sensitive endurance athletes (athlete's paradox).
      We hypothesized that the expression pattern of fatty acid transporters may
      influence oxidative capacity and determine the association between IMCL and
      insulin resistance. OBJECTIVE: The objective of the study was to investigate the
      muscle expression of fatty acid transporters and their function related to
      insulin sensitivity in IMCL-accumulated subjects. DESIGN AND SETTING: The study
      subjects were 36 nonobese healthy men. Their IMCL levels were measured by (1)H
      magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by
      steady-state glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic
      clamp. Gene expression levels in the vastus lateralis were evaluated by
      quantitative RT-PCR. We compared the clinical phenotypes and the expression
      levels of genes involved in lipid metabolism in skeletal muscle between IMCL
      accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR subjects (n = 9). The
      functions of candidate fatty acid transporters were determined by in vitro
      analyses. RESULTS: Compared with the low-GIR group, body fat was lower and
      maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation
      genes in muscle were up-regulated in the H-GIR group, and this was associated
      with increased expression of higher plasma membrane-associated fatty acid-binding
      protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)
      1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation
      coupled with the elevated expression of genes related to fatty acid oxidation.
      These changes were not observed in FATP1-overexpressed myotubes. CONCLUSIONS:
      Differences in the gene expression of fatty acid transporters may, at least in
      part, affect insulin sensitivity in IMCL-accumulated nonobese men.

PMID- 24937541
TI  - A randomized controlled trial of the effects of pioglitazone treatment on
      sympathetic nervous system activity and cardiovascular function in obese subjects
      with metabolic syndrome.
AB  - CONTEXT: Insulin resistance and sympathetic nervous system overactivity are
      closely associated and contribute to cardiovascular risk. OBJECTIVE: The
      objective of the study was to test the hypotheses that pharmacological
      improvement in insulin sensitivity would (1) attenuate sympathetic neural drive
      and (2) enhance neuronal norepinephrine uptake. PARTICIPANTS AND METHODS: A
      randomized, double-blind trial was conducted in 42 obese, unmedicated individuals
      with metabolic syndrome (mean age 56 +/- 1 y, body mass index 34 +/- 0.6 kg/m(2))
      who received 12 weeks of pioglitazone (PIO; 15 mg for 6 wk, then 30 mg daily) or
      matched placebo. Clinical measurements included whole-body norepinephrine
      kinetics [spillover rate, plasma clearance, and the steady state ratio of
      tritiated 3,4-dihydroxyphenylglycol to tritiated norepinephrine ([(3)H]-DHPG to
      [(3)H]-NE) as an index of neuronal uptake-1], muscle sympathetic nerve activity,
      spontaneous baroreflex sensitivity, euglycemic hyperinsulinemic clamp, oral
      glucose tolerance test, ambulatory blood pressure, and Doppler echocardiography.
      RESULTS: PIO treatment increased glucose uptake by 35% and was accompanied by
      significant reductions in diastolic blood pressure and improved left ventricular
      diastolic and endothelial function. Resting muscle sympathetic nerve activity
      burst frequency decreased by -6 +/- 3 burst/min compared with baseline (P = .03),
      but the magnitude of change was not different from placebo (P = .89).
      Norepinephrine spillover and clearance rates and baroreflex sensitivity were
      unchanged. Post hoc subgroup analyses revealed an 83% increase in [(3)H]-DHPG to
      [(3)H]-NE ratio in hyperinsulinemic (P = .04) but not normoinsulinemic subjects
      (time * group interaction, P = .045). Change in [(3)H]-DHPG to [(3)H]-NE ratio
      correlated with improvements in diastolic blood pressure (r = -0.67, P = .002),
      the ratio of early (E) to late (A) peak transmitral diastolic inflow velocity (r
      = 0.62, P = .008), E wave deceleration time (r = -0.48, P = .05), and
      Deltainsulin area under the curve0-120 during the oral glucose tolerance test (r
      = -0.42, P = .08). CONCLUSIONS: Compared with placebo, PIO does not affect
      resting sympathetic drive or norepinephrine disposition in obese subjects with
      metabolic syndrome. Treatment induced changes in the [(3)H]-DHPG to [(3)H]-NE
      ratio related to reduction in hyperinsulinemia and improvements in diastolic
      function.

PMID- 24937542
TI  - Long-term efficacy and safety of pegvisomant in combination with long-acting
      somatostatin analogs in acromegaly.
AB  - BACKGROUND: Treatment for acromegaly patients with long-acting somatotropin
      release-inhibiting factor (LA-SRIF) often does not result in complete
      normalization of IGF-1. Addition of pegvisomant (PEGV), a GH receptor antagonist,
      could improve this; however, the literature has not described long-term follow
      up. OBJECTIVE: To assess long-term efficacy and safety of this combined treatment
      in the largest current single-center cohort of patients, from 2004-2013. DESIGN:
      Acromegaly patients were treated for at least 6 months with a high-dose LA-SRIF.
      To patients with persistently elevated IGF-1 levels (>1.2 * upper limit of
      normal) or poor quality of life, PEGV was added as one weekly injection. RESULTS:
      The patients (n = 141) were treated with PEGV and LA-SRIFs for a median period of
      4.9 years (range, 0.5-9.2). Efficacy, defined as the lowest measured IGF-1 level
      during treatment, was 97.0%. The median PEGV dose to achieve this efficacy was 80
      mg weekly (interquartile range, 60-120 mg). Combination treatment-related adverse
      events were recorded in 26 subjects (18.4%). Pituitary tumor size increase was
      observed in one patient. Injection-site reactions were observed in four subjects.
      In 19 patients (13.5%), transiently elevated liver transaminases of more than
      three times the upper limit of normal were observed, of which 83% occurred within
      the first year of combination treatment. Eight patients died, at a mean age of 71
      years; none of them were considered treatment-related. CONCLUSIONS: The
      combination treatment with LA-SRIFs and PEGV was effective in 97% of the
      patients, it appears to be a safe medical treatment and it reduces the required
      dose of PEGV.

PMID- 24937543
TI  - Sex hormone binding globulin deficiency due to a homozygous missense mutation.
AB  - CONTEXT: SHBG is known as the major sex steroid binding protein in plasma, and it
      regulates the bioavailability of both T and estradiol levels required for effects
      on target tissues. We identified a man with an undetectable SHBG concentration in
      combination with low total T. He presented with a 7-year history of muscle
      weakness, fatigue, and a low libido. OBJECTIVES: To determine the cause of the
      SHBG deficiency, we employed both genetic analysis of the SHBG gene and transgene
      SHBG expression. RESULTS: Genetic analysis identified a novel homozygous missense
      mutation that was predicted to be deleterious for protein function. Transgene
      expression showed that the mutation resulted in a block in SHBG secretion
      accompanied by increased expression of the endoplasmic reticulum molecular
      chaperone HSPA5. The mutation results in accumulation of the mutant SHBG within
      the cell and failure to secrete the mutant protein. Screening of family members
      identified one sister who was also deficient for SHBG. CONCLUSIONS: We have
      identified a family with a missense mutation within the SHBG gene, which results
      in a complete deficiency of plasma SHBG in the homozygous state. Although total T
      level was low in the male patient, it did not interfere with normal gonadal
      development and spermatogenesis, suggesting a limited role of SHBG in sexual
      maturation and male physiology.

PMID- 24937544
TI  - Behavioral and neural correlates of executive functioning in musicians and non
      musicians.
AB  - Executive functions (EF) are cognitive capacities that allow for planned,
      controlled behavior and strongly correlate with academic abilities. Several
      extracurricular activities have been shown to improve EF, however, the
      relationship between musical training and EF remains unclear due to
      methodological limitations in previous studies. To explore this further, two
      experiments were performed; one with 30 adults with and without musical training
      and one with 27 musically trained and untrained children (matched for general
      cognitive abilities and socioeconomic variables) with a standardized EF battery.
      Furthermore, the neural correlates of EF skills in musically trained and
      untrained children were investigated using fMRI. Adult musicians compared to non
      musicians showed enhanced performance on measures of cognitive flexibility,
      working memory, and verbal fluency. Musically trained children showed enhanced
      performance on measures of verbal fluency and processing speed, and significantly
      greater activation in pre-SMA/SMA and right VLPFC during rule representation and
      task-switching compared to musically untrained children. Overall, musicians show
      enhanced performance on several constructs of EF, and musically trained children
      further show heightened brain activation in traditional EF regions during task
      switching. These results support the working hypothesis that musical training may
      promote the development and maintenance of certain EF skills, which could mediate
      the previously reported links between musical training and enhanced cognitive
      skills and academic achievement. 

PMID- 24937545
TI  - Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder:
      a noninvasive biomarker that responds to psychostimulant treatment?
AB  - PURPOSE: To comprehensively assess brain iron levels in typically developing
      control subjects and patients with attention deficit hyperactivity disorder
      (ADHD) when psychostimulant medication history is accounted for. MATERIALS AND
      METHODS: This prospective study was approved by the institutional review board,
      and informed consent was obtained. Brain iron was indexed noninvasively by using
      magnetic resonance (MR) imaging relaxation rates (R2, R2*, R2') and magnetic
      field correlation (MFC) in the globus pallidus, putamen, caudate nucleus, and
      thalamus for 22 patients with ADHD (12 medication-naive patients and 10 with a
      history of psychostimulant treatment) and 27 control subjects (age range, 8-18
      years). Serum iron measures were also collected. Subgroup differences were
      analyzed with data-appropriate omnibus tests followed by post hoc pairwise
      comparisons; false discovery rate correction was conducted to control for
      multiple comparisons. RESULTS: Medication-naive ADHD patients had significantly
      lower striatal and thalamic MFC indexes of brain iron than did control subjects
      (putamen, P = .012; caudate nucleus, P = .008; thalamus, P = .012) and
      psychostimulant-medicated ADHD patients (putamen, P = .006; caudate nucleus, P =
      .010; thalamus, P = .021). Conversely, the MFC indexes in medicated patients were
      comparable to those in control subjects. No significant differences were detected
      with R2, R2*, R2', or serum measures. CONCLUSION: Lower MFC indexes of striatal
      and thalamic brain iron in medication-naive ADHD patients and lack of differences
      in psychostimulant-medicated patients suggest that MFC indexes of brain iron may
      represent a noninvasive diagnostic biomarker that responds to psychostimulant
      treatment.

PMID- 24937547
TI  - American Pediatric Society 2014 presidential address: the thrill of discovery
      (and other foundations of biomedical research).

PMID- 24937546
TI  - Vitamin D and fetal-neonatal calcium homeostasis: findings from a randomized
      controlled trial of high-dose antenatal vitamin D supplementation.
AB  - BACKGROUND: There is current interest in the maternal-fetal effects of antenatal
      vitamin D supplementation, yet little data regarding vitamin D's role in neonatal
      calcium homeostasis. We determined to assess the effect of high-dose antenatal
      vitamin D supplementation on fetal and neonatal calcium concentrations. METHODS:
      In a double-blinded, placebo-controlled trial in Bangladesh, 160 pregnant women
      were randomized to oral vitamin D3 (35,000 IU/wk) or placebo from 26 to 29 wk of
      gestation. RESULTS: Total serum calcium (Ca) was higher in cord blood of those
      supplemented vs. placebo (2.66 +/- 0.1 vs. 2.61 +/- 0.2 mmol/l; P = 0.04), but
      the difference in albumin-adjusted calcium was not statistically significant.
      Change in Ca concentration from birth to day 3 of life was attenuated by vitamin
      D (-0.10 +/- 0.17) compared with placebo (-0.22 +/- 0.18 mmol/l; P = 0.02).
      Maternal 25-hydroxyvitamin D (25(OH)D) (P = 0.04) and cord 25(OH)D (P < 0.01)
      were associated with day 3 infant Ca, suggesting that the effect of
      supplementation was mediated by change in maternal-infant vitamin D status. Six
      infants in each of the supplemented and placebo groups had transient
      hypercalcemia/hypercalcuria; in all the hypercalcemia/hypercalcuria was
      asymptomatic, spontaneously resolved, and unassociated with nephrocalcinosis at 1
      mo of life. CONCLUSION: High-dose antenatal third-trimester vitamin D
      supplementation attenuated the early postnatal calcium nadir, without increasing
      the risk of postnatal hypercalcemia.

PMID- 24937548
TI  - Injectable poly(organophosphazene) hydrogel system for effective paclitaxel and
      doxorubicin combination therapy.
AB  - Combination therapy is an important option for gastric cancer which is the second
      leading cause of cancer-related death worldwide. The administration schedule of
      cell cycle-specific drugs, such as doxorubicin (DOX) and paclitaxel (PTX), is
      important for therapeutic efficacy. However, to control the schedule is
      clinically inconvenient. Additionally, in vitro cytotoxicity tests against human
      gastric cancer cells (SNU-601) showed that the combination indices (CIs) of DOX
      and PTX were 1.43 (alpha=0) and 1.90 (alpha=1), respectively, indicating that the
      DOX and PTX interaction was antagonistic. Thus, based on the finding that the
      release rate of drugs from poly(organophosphazene) (PPZ) hydrogel is dependent on
      the hydrophobicity of the drugs, we used injectable PPZ hydrogel in combination
      therapy. In vivo anticancer activity test in human gastric cancer cell
      xenografted mice showed that intratumoral injection with aqueous PPZ solution,
      containing DOX (15 mg/kg) and PTX (30 mg/kg), resulted in the highest tumor
      inhibition and safety (no mortality for approximately 3 months) in the
      experimental groups. Consequently, PPZ hydrogel is expected to be a promising
      drug delivery system for cell cycle-specific drugs, facilitating the control of
      their administration schedule for effective combination therapy.

PMID- 24937549
TI  - Prediction of the structure of a silk-like protein in oligomeric states using
      explicit and implicit solvent models.
AB  - We perform Replica Exchange Molecular Dynamics (REMD) simulations on a silk-like
      protein design with amino-acid sequence [(Gly-Ala)3-Gly-Glu]5 to investigate the
      stability of a single protein, a dimer, a trimer and a tetramer made up of these
      proteins starting from beta-roll and beta-sheet structures in both explicit
      (TIP3P) and implicit (GBSA) solvent models. Our simulation results for the
      implicit solvent model agree with those for the explicit solvent model for
      simulation times up to the longest tested, being 30 ns per replica. From this we
      infer that the implicit solvent model that we use is reliable, allowing us to
      reach much longer time scales (up to 200 ns per replica). We find that the self
      assembly of fibers of these proteins in solution must be a nucleated process,
      involving nuclei made up of at least three monomers. We also find that the
      conformation of the protein changes upon assembly, i.e., there is a transition
      from a disordered globular state to an ordered beta-sheet structure in the self
      assembled state of aggregates containing more than two monomers. This indicates
      that autosteric effects must be important in the polymerization of this protein,
      reminiscent of what is observed for beta-amyloids. Our findings are consistent
      with recent experimental results on a protein with an amino acid sequence similar
      to that of the protein we study. 

PMID- 24937550
TI  - Cyclone-induced rapid creation of extreme Antarctic sea ice conditions.
AB  - Two polar vessels, Akademik Shokalskiy and Xuelong, were trapped by thick sea ice
      in the Antarctic coastal region just to the west of 144 degrees E and between
      66.5 degrees S and 67 degrees S in late December 2013. This event demonstrated
      the rapid establishment of extreme Antarctic sea ice conditions on synoptic time
      scales. The event was associated with cyclones that developed at lower latitudes.
      Near the event site, cyclone-enhanced strong southeasterly katabatic winds drove
      large westward drifts of ice floes. In addition, the cyclones also gave southward
      ice drift. The arrival and grounding of Iceberg B9B in Commonwealth Bay in March
      2011 led to the growth of fast ice around it, forming a northward protruding
      barrier. This barrier blocked the westward ice drift and hence aided sea ice
      consolidation on its eastern side. Similar cyclone-induced events have occurred
      at this site in the past after the grounding of Iceberg B9B. Future events may be
      predictable on synoptic time scales, if cyclone-induced strong wind events can be
      predicted. 

PMID- 24937552
TI  - Editorial.

PMID- 24937551
TI  - A treatment planning and delivery comparison of volumetric modulated arc therapy
      with or without flattening filter for gliomas, brain metastases, prostate,
      head/neck and early stage lung cancer.
AB  - BACKGROUND: Flattening filter-free (FFF) beams are an emerging technology that
      has not yet been widely implemented as standard practice in radiotherapy centers.
      To facilitate the clinical implementation of FFF, we attempted to elucidate the
      difference in plan quality and treatment delivery time compared to flattening
      filter beams (i.e. standard, STD) for several patient groups. We hypothesize that
      the treatment plan quality is comparable while the treatment delivery time of
      volumetric modulated arc therapy (VMAT) is considerably shorter using FFF beams,
      especially for stereotactic treatments. METHODS: A total of 120 patients treated
      for head and neck (H&N) tumors, high-grade glioma, prostate cancer, early stage
      lung cancer and intra-cranial metastatic disease (both single and multiple
      metastases) were included in the study. For each cohort, 20 consecutive patients
      were selected. The plans were generated using STD- and FFF-VMAT for both 6 MV and
      10 MV, and were compared with respect to plan quality, monitor units and delivery
      time using Wilcoxon signed rank tests. RESULTS: For H&N and high-grade gliomas,
      there was a significant difference in homogeneity index in favor for STD-VMAT (p
      < 0.001). For the stereotactic sites there were no differences in plan
      conformity. Stereotactic FFF-VMAT plans required significantly shorter delivery
      time compared to STD-VMAT plans (p < 0.001) for higher dose per fraction, on
      average 54.5% for 6 MV and 71.4% for 10 MV. FFF-VMAT generally required a higher
      number of MU/Gy (p < 0.001), on average 7.0% for 6 MV and 8.4% for 10 MV.
      CONCLUSION: It was generally possible to produce FFF-VMAT plans with the same
      target dose coverage and doses to organs at risk as STD-VMAT plans. Target dose
      homogeneity tended to be somewhat inferior for FFF-VMAT for the larger targets
      investigated. For stereotactic radiotherapy, FFF-VMAT resulted in a considerable
      time gain while maintaining similar plan quality compared to STD beams.

PMID- 24937553
TI  - Is there a role for psychiatry in deepening our understanding of the "suicide
      bomber"?

PMID- 24937554
TI  - The influence of neurocognitive dysfunctions on work capacity in schizophrenia
      patients: a systematic review of the literature.
AB  - Objective. The aim of the study was to review empirical studies of the influence
      of neurocognitive dysfunctions on work capacity (i.e. the ability to obtain and
      maintain competitive work as well as different aspects of work behaviour and
      skills in relation to job requirements) in schizophrenia patients. An
      investigation of the extent of symptoms compared to neurocognitive functioning on
      work capacity in schizophrenia patients is included. Method. A literature search
      for studies in the English language was made in the databases PubMed, PsycInfo
      and EMBASE. Twenty-one studies were selected for thorough evaluation. Results.
      Neurocognitive functioning influences employment, work rehabilitation, work
      skills and work behaviour in various ways among schizophrenia patients. Moreover,
      symptoms seem less important to work capacity than neurocognitive functioning.
      Some guidelines can be drawn from the research studies to provide clinicians with
      indicators for the assessment of neurocognitive functioning in relation to work
      capacity and rehabilitation. Conclusions. Despite different methodological
      limitations in the reviewed studies, evidence is presented for a crucial
      relationship between neurocognitive functioning and work capacity among patients
      with schizophrenia. At present, the evidence is strong enough to argue that the
      individual neurocognitive profile should be taken into account before planning
      work rehabilitation. 

PMID- 24937555
TI  - Partial compliance with antipsychotics and its impact on patient outcomes.
AB  - Partial compliance with antipsychotic medications is a common and complex
      phenomenon that is underestimated by physicians. The consequences of partial
      compliance include an increased risk of relapse, rehospitalization and suicide
      attempts. Stigma, negative attitudes towards medications, cognitive impairment
      and diminished insight negatively impact treatment adherence. Oral atypical
      antipsychotics may improve both insight and cognitive function, but compliance
      with these agents is not assured. Depot conventional antipsychotics ensure
      medication delivery but are associated with side-effects such as EPS and
      dysphoria that decrease compliance. Long-acting atypicals provide significant
      symptom improvement, foster adherence and may help achieve improvement in insight
      and cognition. Addressing issues of partial and non-compliance is a significant
      consideration in relapse prevention strategies for patients with schizophrenia,
      given the devastating consequences associated with psychotic relapses. 

PMID- 24937556
TI  - Quetiapine demonstrates good tolerability and is associated with improvements in
      extrapyramidal symptoms in patients with schizophrenia switched from other
      antipsychotics: results of a naturalistic study.
AB  - Objectives. Compared with conventional agents, atypical antipsychotics such as
      quetiapine (Seroquel(r); AstraZeneca) show improved tolerability and a lower
      liability to cause extrapyramidal symptoms (EPS). In the routine treatment of
      schizophrenia, it is usual practice to consider a change of medication when the
      current treatment is ineffective or poorly tolerated, although few studies are
      available to guide clinicians. This paper reports the results from the Seroquel
      Method. Patient Evaluation on Changing Treatment Relative to Usual Medication
      (SPECTRUM) trial, a 12-week, open-label, noncomparative study that evaluated
      clinical benefit and tolerability of switching patients with schizophrenia from
      their existing antipsychotic to quetiapine. Patients were switched because of
      intolerance to, or lack of efficacy with, their previous antipsychotic.
      Quetiapine was titrated to 400 mg/day over 7 days, then dosed flexibly up to 750
      mg/day over the remaining weeks (mean modal dose 505 mg/day). Results. In the
      overall population of 506 evaluable patients, quetiapine was well tolerated, with
      a low incidence of adverse events and minimal requirement for anticholinergic
      medication. Significant improvements in EPS, including parkinsonism and
      akathisia, were observed, irrespective of reason for switching, although greatest
      improvements were observed in patients switching because of EPS. Conclusions.
      This study provides further evidence for the utility and tolerability of
      quetiapine, in patients with schizophrenia who had been switched from a previous
      antipsychotic, following problems with efficacy or tolerability. 

PMID- 24937557
TI  - Efficacy and tolerability of quetiapine in cluster B personality disorder: an
      open-label study.
AB  - Objective. The aim of this open-label 8-week study was to assess the
      effectiveness of quetiapine on aggressive behaviour and social dysfunctions in
      patients suffering from a cluster B personality disorder (DSM-IV). Methods. The
      visits were performed at baseline and at days 14, 28 and 56. After a standard
      titration schedule, the patients received a dose augmented or reduced dose,
      within a range from 50 to 400 mg/day during the visits, depending on efficacy and
      tolerance. Assessment of efficacy was based on the French version of the Social
      Disability and Aggression Scale SDAS (SDAS-21). Response was defined as a
      decrease of >=50% reduction of the total scores compared to baseline.
      Tolerability was assessed with the CGI, UKU, EPS-scales. Results and conclusion.
      Eight of the 12 patients included received 200 mg/day quetiapine after titration
      (all patients: 50-400 mg/day). At week 8, five out of 12 patients were responders
      based on the SDAS-21 scores for the average expression of the symptoms, and six
      out of 12 on the basis of SDAS-21 scores for the peak expression. There was a
      significant correlation between weight change and total SDAS variation (Kendall's
      taub= -0.644; p=0.02). These findings should be reexamined in further studies. 

PMID- 24937558
TI  - Effectiveness of antidepressants in the treatment of major depressive disorder in
      Latin America.
AB  - Objective. Painful physical symptoms occur frequently in patients with major
      depressive disorder (MDD), and although numerous studies report the effect of
      antidepressants on emotional aspects of depression, few focus on their effect on
      physical symptoms. This observational study was conducted, in a clinical practice
      setting, to determine antidepressant treatment decisions and their outcome on the
      physical and emotional symptoms of MDD. Methods. Patients with a mean score >=2
      for pain-related items on the Somatic Symptom Inventory (SSI) were classified
      with painful physical symptoms (PPS +) and differentiated from the remaining
      patients (PPS -). Severity of depression and physical pain were determined using
      the 17-item Hamilton Depression Rating Scale (HAMD17) and Clinical Global
      Impressions of Severity Scale (CGI-S), and Visual Analog Scale (VAS),
      respectively. Results. At baseline, 72.6% of patients were PPS+. Compared to PPS-
      patients, PPS +patients were, on average, significantly more depressed at
      baseline (mean difference [95% CI]: HAMD17 4.6 [3.6, 5.5] and CGI-S 0.3 [0.2,
      0.4]; all p<0.0001), and remained more depressed and in greater pain at endpoint
      (HAMD17p=0.0074, CGI-S P =0.0151, and VAS P <0.0001). In addition, fewer PPS+
      patients (65.8%) achieved remission (total HAMD17<=7) compared to PPS- patients
      (74.6%, P =0.0180). Conclusions. Painful physical symptoms are prevalent in MDD
      patients, highlighting the importance of addressing both the physical and
      emotional symptoms of depression. 

PMID- 24937559
TI  - Alexithymia and anxiety sensitivity in Turkish depressive, anxiety and somatoform
      disorder outpatients *.
AB  - Objective. To assess the relations between anxiety sensitivity, and dimensions of
      alexithymia in somatoform, anxiety and depressive disorder patients. Methods. The
      sample consisted of 124 patients with the diagnosis of depressive, anxiety, or
      somatoform spectrum disorders (DSM-IV). Toronto Alexithymia Scale (TAS-20), 16
      item Anxiety Sensitivity Index (ASI), Hamilton Depression (HDRS), and Anxiety
      (HAS) scales were used. Results. The total sample (n=124) was divided into three
      diagnostic categories. There was one Depression Group (n=69). Due to small sample
      sizes, diagnoses in anxiety and somatoform spectrum disorders were combined in
      two relatively larger Anxiety (n=42) and Somatoform Groups (n=13) for statistical
      purposes. No statistically significant difference was found in the TAS-20 total
      or subscale scores between the three diagnostic groups. In all three diagnostic
      groups, there was a strong and significant positive correlation between ASI and
      TAS-20 total scores. In all three groups, there was a significant positive
      correlation between TAS-20 Factor 1 and ASI. In the Depression and Somatoform
      Groups, ASI scores were found to be significantly positively correlated with
      scores on TAS-20 Factor 2. Conclusion. This study reveals that alexithymia does
      not differentiate depressive, anxiety, or somatoform disorders, yet suggests a
      functional relation with anxiety sensitivity on a subscale basis. 

PMID- 24937560
TI  - The sufficiency of the HAM-D6 as an outcome instrument in the acute therapy of
      antidepressants in the outpatient setting.
AB  - Objective. To re-analyse the Spanish outpatient study on the various versions of
      the Hamilton Depression Scale (HAM-D) by using item-response theory models for
      measuring unidimensionality. Methods. The Mokken analysis, based on the
      coefficient of homogeneity, was used. A coefficient of 0.40 or higher was
      accepted for unidimensionality. The three HAM-D versions were compared: HAM-D6
      (core items of depression), HAM-D17 and HAM-D21. Results. In total, 113 of the
      116 patients included in the study completed the planned treatment period of 6
      weeks. As the Mokken analysis depends as much on the sample of patients under
      examination (dispersion of scores on the item) as on the scale itself, the
      endpoint was used. For HAM-D6, but not for HAM-D17 or HAM-D21, the coefficient of
      homogeneity was acceptable (0.44). Conclusion. The HAM-D6 is a valid version of
      the Hamilton Scale to be recommended for monitoring depressed patients in
      antidepressant therapy in the outpatient setting. 

PMID- 24937561
TI  - Antipsychotic use in a first episode psychosis program.
AB  - Objective. To conduct a naturalistic, longitudinal study of prescribing patterns
      of atypical neuroleptics in predominantly drug-naive first episode non-affective
      psychosis patients. Methods. Patients with a first episode psychosis were
      prescribed an antipsychotic as part of a clinical protocol and followed-up for 2
      years. Comparisons were made between risperidone and olanzapine, the two most
      commonly prescribed antipsychotics. Socio-demographic variables and clinical
      characteristics such as diagnosis, duration of untreated illness and psychosis
      and level of positive and negative symptoms were assessed using well-established
      methods. We examined the first antipsychotic given, starting dose, time taken to
      start and to reach the maximum dose, time on first medication, maximum dose,
      medication change and concomitant medication use. Results. One hundred and ninety
      three consecutive patients consented to start on antipsychotic. The results are
      provided for risperidone (N = 133) and olanzapine (N=38). The time to initiate
      antipsychotic medications was significantly longer for outpatients than
      inpatients. There were no differences between the two groups for time taken to
      reach the maximum dose, drop out rates or concomitant medication use. The
      percentage of patients taking an antipsychotic agent at any given time was high
      (range 79-91%), but half of the patients had changed from their first
      antipsychotic by 6 months. CONCLUSIONS: The reality of clinical practice can be
      much different than rigid protocols or treatment algorithms of pre-marketing
      studies or clinical trials. In this sample of first episode psychosis patients,
      although the majority of patients remained on an antipsychotic, changes in
      medication over the first 2 years were common. Polypharmacy was not a common
      practice.

PMID- 24937562
TI  - Prevalence of childhood attention deficit hyperactivity disorder in opiate
      dependent adults.
AB  - Background. There is a clear association between childhood attention deficit
      hyperactivity disorder and substance use disorders in adulthood. Symptoms of
      attention deficit disorder may also persist into adulthood. The study aimed to
      determine the prevalence of childhood ADHD in a sample of treatment seeking
      opiate-dependent adults. Methods. Treatment-seeking opiate-dependent subjects
      completed the Utah adult ADHD screening test and the self-report early
      delinquency scale. Results. A total of 15% were "likely" and 49 were "highly
      likely" to have suffered ADHD in childhood. The averages scores for the
      delinquency scales were over 6 times those reported from population norms.
      Conclusion. Symptoms of childhood ADHD is common in adults with opiate
      dependence. The residual symptoms in adults should be investigated as may be
      amenable to newer treatments for adult attention deficit disorder. 

PMID- 24937563
TI  - Suicide attempts and domestic violence among women psychiatric inpatients.
AB  - Objective. Previous clinical observations, as well as empirical studies in fairly
      unique samples, suggest that there may be a relationship between domestic
      violence victimization and suicide attempts. We wished to examine this
      relationship among psychiatric women inpatients. Methods. In this study among
      psychiatric inpatients, we compared women with versus without suicide attempts
      with regard to scores on a measure of domestic violence. Results. Compared to
      women without attempts, women with acknowledged histories of suicide attempts had
      significantly higher scores on the measure of domestic violence. Conclusion.
      These data support a relationship between domestic-violence victimization and a
      history of suicide attempts. From the perspective of assessment, inpatient
      clinicians need to carefully screen every patient with a history of suicide
      attempts for a history of domestic violence. 

PMID- 24937564
TI  - Bispectral index for improving anaesthetic delivery and postoperative recovery.
AB  - BACKGROUND: The use of clinical signs may not be reliable in measuring the
      hypnotic component of anaesthesia. The use of bispectral index (BIS) to guide the
      dose of anaesthetic may have certain advantages over clinical signs. This is the
      second update of a review originally published in 2007. OBJECTIVES: The primary
      objective of this review focused on whether the incorporation of BIS into the
      standard practice for management of anaesthesia can reduce the risk of
      intraoperative awareness, consumption of anaesthetic agents, recovery time and
      total cost of anaesthesia in surgical patients undergoing general anaesthesia.
      SEARCH METHODS: In this updated version, we searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1),
      MEDLINE (1990 to 31 January 2013), EMBASE (1990 to 31 January 2013) and reference
      lists of articles. Previously, we searched to May 2009. SELECTION CRITERIA: We
      included randomized controlled trials comparing BIS with standard practice
      criteria for titration of anaesthetic agents. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial quality, extracted data and analysed the
      data. We contacted study authors for further details. MAIN RESULTS: We included
      36 trials. In studies using clinical signs as standard practice, the results
      demonstrated a significant effect of the BIS-guided anaesthesia in reducing the
      risk of intraoperative awareness among surgical patients at high risk for
      awareness (7761 participants; odds ratio (OR) 0.24, 95% confidence interval (CI)
      0.12 to 0.48). This effect was not demonstrated in studies using end tidal
      anaesthetic gas (ETAG) monitoring as standard practice (26,530 participants; OR
      1.13, 95% CI 0.56 to 2.26). BIS-guided anaesthesia reduced the requirement for
      propofol by 1.32 mg/kg/hr (672 participants; 95% CI -1.91 to -0.73) and for
      volatile anaesthetics (desflurane, sevoflurane, isoflurane) by 0.65 minimal
      alveolar concentration equivalents (MAC) (95% CI -1.01 to -0.28) in 985
      participants. Irrespective of the anaesthetics used, BIS reduced the following
      recovery times: time for eye opening (2557 participants; by 1.93 min, 95% CI 
      2.70 to -1.16), response to verbal command (777 participants; by 2.73 min, 95% CI
      -3.92 to -1.54), time to extubation (1501 participants; by 2.62 min, 95% CI -3.46
      to -1.78), and time to orientation (373 participants; by 3.06 min, 95% CI -3.63
      to -2.50). BIS shortened the duration of postanaesthesia care unit stay by 6.75
      min (1953 participants; 95% CI -11.20 to -2.31) but did not significantly reduce
      the time to home readiness (329 participants; -7.01 min, 95% CI -30.11 to 16.09).
      AUTHORS' CONCLUSIONS: BIS-guided anaesthesia can reduce the risk of
      intraoperative awareness in surgical patients at high risk for awareness in
      comparison to using clinical signs as a guide for anaesthetic depth. BIS-guided
      anaesthesia and ETAG-guided anaesthesia may be equivalent in protection against
      intraoperative awareness but the evidence for this is inconclusive. In addition,
      anaesthesia guided by BIS kept within the recommended range improves anaesthetic
      delivery and postoperative recovery from relatively deep anaesthesia.

PMID- 24937566
TI  - Cationic gold catalyst poisoning and reactivation.
AB  - High gold affinity impurities (halides, bases) in solvents, starting materials,
      filtration, or drying agents could affect the reactivity of gold catalyst
      adversely, which may significantly reduce the TON of cationic gold-catalyzed
      reactions. Use of a suitable acid activator (e.g., HOTf, In(OTf)3) reactivates
      the gold catalyst and makes the reaction proceed smoothly at low gold catalyst
      loading. 

PMID- 24937565
TI  - The billion cell construct: will three-dimensional printing get us there?
AB  - How structure relates to function--across spatial scales, from the single
      molecule to the whole organism--is a central theme in biology. Bioengineers,
      however, wrestle with the converse question: will function follow form? That is,
      we struggle to approximate the architecture of living tissues experimentally,
      hoping that the structure we create will lead to the function we desire. A new
      means to explore the relationship between form and function in living tissue has
      arrived with three-dimensional printing, but the technology is not without
      limitations.

PMID- 24937568
TI  - Complete mitochondrial genome of a Asian lion (Panthera leo goojratensis).
AB  - The entire mitochondrial genome of this Asian lion (Panthera leo goojratensis)
      was 17,183 bp in length, gene composition and arrangement conformed to other
      lions, which contained the typical structure of 22 tRNAs, 2 rRNAs, 13 protein
      coding genes and a non-coding region. The characteristic of the mitochondrial
      genome was analyzed in detail. 

PMID- 24937567
TI  - Identification of virulence determinants in influenza viruses.
AB  - To date there is no rapid method to screen for highly pathogenic avian influenza
      strains that may be indicators of future pandemics. We report here the first
      development of an oligonucleotide-based spectroscopic assay to rapidly and
      sensitively detect a N66S mutation in the gene coding for the PB1-F2 protein
      associated with increased virulence in highly pathogenic pandemic influenza
      viruses. 5'-Thiolated ssDNA oligonucleotides were employed as probes to capture
      RNA isolated from six influenza viruses, three having N66S mutations, two without
      the N66S mutation, and one deletion mutant not encoding the PB1-F2 protein.
      Hybridization was detected without amplification or labeling using the intrinsic
      surfaced-enhanced Raman spectrum of the DNA-RNA complex. Multivariate analysis
      identified target RNA binding from noncomplementary sequences with 100%
      sensitivity, 100% selectivity, and 100% correct classification in the test data
      set. These results establish that optical-based diagnostic methods are able to
      directly identify diagnostic indicators of virulence linked to highly pathogenic
      pandemic influenza viruses without amplification or labeling. 

PMID- 24937569
TI  - The complete mitochondrial genome of the African palm civet, Nandinia binotata,
      the only representative of the family Nandiniidae (Mammalia, Carnivora).
AB  - Here I report the complete mitochondrial genome of the African palm civet,
      (Nandinia binotata) as sequenced from overlapping PCR products. The genome is
      17,103 bp in length and contains the 37 genes found in a typical mammalian
      genome: 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes.
      The control region of N. binotata includes both RS2 and RS3 tandem repeats. The
      overall base composition on the L-strand is A: 33.6%, C: 27.3%, G: 13.0%, and T:
      26.1%. 

PMID- 24937570
TI  - The complete mitochondrial genome of cultivated radish WK10039 (Raphanus sativus
      L.).
AB  - We determined the complete nucleotide sequence of the mitochondrial genome of
      radish cultivar WK10039 (Raphanus sativus L.). The total length of the mtDNA
      sequence is 244,054 bp, with GC content of 45.3%. The radish mtDNA contains 82
      protein-coding genes, 17 tRNA genes, and 3 rRNA genes. Among the protein-coding
      genes, 34 encode proteins with known functions. There are two 5529 bp repeats in
      the radish mitochondrial genome that may contribute to DNA recombination
      resulting in at least three different forms of mtDNA in radish. 

PMID- 24937571
TI  - The complete mitochondrial genome of the Servaline Genet, Genetta servalina, the
      first representative from the family Viverridae (Mammalia, Carnivora).
AB  - Here I report the complete mitochondrial genome of the Servaline Genet, Genetta
      servalina, as sequenced from overlapping PCR products. The genome is 16,938 base
      pairs in length and contains the 37 genes found in a typical mammalian genome: 13
      protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The
      control region of G. servalina includes both RS2 and RS3 tandem repeats. The
      overall base composition on the L-strand is A: 32.8%, C: 25.5%, G: 13.5%, and T:
      28.2%. 

PMID- 24937572
TI  - The complete mitochondrial genome of Jinshaia sinensis (Teleostei, Balitoridae,
      Balitorinae).
AB  - Jinshaia sinensis is an endemic and typical fish which is successfully adaptive
      to mountain torrents in the upper stream of the Yangtze River and its
      tributaries. In this study, the complete mitogenome sequence of J. sinensis has
      been first sequenced by DNA sequencing based on the PCR fragments. The
      mitogenome, consisting of 16,567 base pairs (bp), had typical vertebrate
      mitochondrial gene arrangement, including 13 protein coding genes, 22 transfer
      RNAs, 2 ribosomal RNA genes and a noncoding control region (CR). The overall base
      composition of J. sinensis is 30.37% A, 28.82% C, 16.59% G, and 24.22% T, with a
      relatively a slight AT bias of 54.59%. CR of 903 bp length is located between
      tRNA(Pro) and tRNA(Phe). The complete mitochondrial genome may provide
      fundamental informative data not only for unravel the population structure and
      differentiation, but also for further conservation genetics studies on this
      balitorid species. 

PMID- 24937573
TI  - The complete mitochondrial genome of the Spotted Linsang, Prionodon pardicolor,
      the first representative from the family Prionodontidae (Mammalia, Carnivora).
AB  - The complete mitochondrial genome of the Spotted Linsang, Prionodon pardicolor,
      was sequenced using overlapping PCR products. The genome is 16,718 base pairs in
      length and contains the 37 genes found in a typical mammalian genome: 13 protein
      coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The overall base
      composition on the L-strand is A: 32.4%, C: 25.0%, G: 13.9%, T: 28.7%. The
      control region of P. pardicolor includes both RS2 and RS3 tandem repeats.
      Phylogenetic analyses support a sister relationship with the Felidae. 

PMID- 24937574
TI  - Mitochondrial genome of Dinodon rufozonatum (Squamata: Colubridae: Dinodon).
AB  - Dinodon rufozonatum is a species of nocturnal snake in the family Colubridae,
      which is native to East Asia. In this study, we determined the complete
      mitochondrial genome of D. rufozonatum. The results showed that the total length
      of the mitogenome was 17,188 bp and contained 13 protein-coding genes, 22
      transfer RNA genes, 2 ribosomal RNA genes, 2 control regions and 1 stem-loop
      region. Overall base composition of the complete mitochondrial DNA was A
      (34.37%), G (12.61%), C (28.24%), and T (24.78%), so the percentage of A and T
      (59.15%) was slightly higher than G and C. All the genes in D. rufozonatum were
      distributed on the H-strand, except for the ND6 subunit gene and ten transfer RNA
      genes which were encoded on the L-strand.

PMID- 24937575
TI  - The complete mitochondrial genome of the boky-boky, Mungotictis decemlineata, the
      first representative of the Malagasy carnivores (Mammalia, Carnivora,
      Eupleridae).
AB  - The complete mitochondrial genome of the boky-boky, Mungotictis decemlineata, was
      sequenced using overlapping PCRs. The genome is 16,910 base pairs in length and
      contains the 37 genes found in a typical mammalian genome: 13 protein-coding
      genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The overall base
      composition on the L-strand is A: 32.1%, C: 27.8%, G: 14.5%, T: 25.6%. The
      control region of M. decemlineata includes both RS2 and RS3 tandem repeats. 

PMID- 24937576
TI  - Editorial.

PMID- 24937577
TI  - DSM-IV Major Depressive Episode criteria: An evaluation of reliability and
      validity across three different rating methods.
AB  - This study examined the reliability and validity of the DSM-IV Major Depressive
      Episode (MDE) symptoms in a sample of outpatients based on clinician ratings of
      assessment interviews, videotape of these interviews, and chart information. A
      group of 44 patients admitted to a university based outpatient community clinic
      were rated by trained clinicians on the nine MDE symptom criteria (A1-A9).
      Patients also completed a self-report measure of depressive symptomatology.
      Interrater reliability was found to be highest between the interview and
      videotape ratings. Conversely, when comparing chart ratings with those made from
      either interview or videotape, reliability for many of the individual criteria
      were found to be in the poor range of reliability. Good internal consistency was
      found for both the interview and videotape ratings, while internal consistency
      was less adequate for chart-based ratings. However, the three MDE ratings
      converge on a single dimension in a similar manner regardless of which source
      (i.e. interview, videotape, or chart) provided the rating. Additional analyses
      revealed a consistent relationship between the three MDE ratings (interview,
      videotape, and chart) with measures of patient reported depressive symptoms that
      exceeded the relationship between these scores with global levels/severity of
      psychopathology. The effects of longer interviews as well as examining depressive
      symptoms within the context of interpersonal functioning is discussed regarding
      the reliable assessment of depressive symptomatology in the mild to moderate
      range of severity. (Int J Psych Can Pract 2004; 8: 3-10). 

PMID- 24937578
TI  - Adaptation of revised Brief PHQ (Brief-PHQ-r) for diagnosis of depression, panic
      disorder and somatoform disorder in primary healthcare settings.
AB  - OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of the
      Turkish version of the revised Brief Patient Health Questionnaire (Brief PHQ-r)
      in depression, panic disorder and somatoform disorder, in primary care settings.
      METHODS: This was a cross-sectional study with blinded psychiatric evaluation.
      The study was conducted at three sites which provide primary health services.
      Total number of the participants was 1556. Of these, 1387 comprised the analysis
      population. Diagnoses of depression, panic disorder and somatoform disorder made
      according to the patient's responses to the questions on Brief PHQ-r form were
      compared with the diagnoses made by psychiatrists using DSM-W. RESULTS:
      Diagnostic performance parameters of Brief PHQ-r were calculated. Main results
      are as follows: for any diagnosis k = 0.567, sensitivity 79.0%, specificity
      82.9%; for major/minor depressive disorder k = 0.536, sensitivity 76.0%,
      specificity 85.3%; for panic disorder k = 0.640, sensitivity 74.4%, specificity
      98.4% and for somatoform disorder k = 0.476, sensitivity 61.9% and specificity
      92.5%. CONCLUSIONS: Diagnostic performance of Brief PHQ-r was found to be quite
      good in the diagnosis of major/minor depressive disorder, panic disorder and
      somatoform disorder, in primary healthcare settings. We recommend its use in
      routine clinical practice in order to help primary healthcare physicians, and
      also infield surveys on psychiatric disorders. Qnt] Psych Clin Pract 2004; 8: 11
      18).

PMID- 24937579
TI  - Comparison between paroxetine and behaviour therapy in patients with
      posttraumatic stress disorder (PTSD): A pilot study.
AB  - Antidepressants and cognitive-behavioural therapy (CBT) have been reported to
      decrease severity of psychopathology in PTSD-patients. To date, no study has been
      carried out which compares psychopharmacolo-gical and psychotherapeutic
      treatments. In a randomized pilot study, PTSD-patients were treated either with
      paroxetine or CBT. Diagnoses were made by structured clinical interviews (ADIS,
      CAPS). The duration of treatment was 3 months; the paroxetine dosage was 10-50
      mg; exposure and cognitive restructuring were the main elements in cognitive
      behavioural therapy. Twenty-one patients were included. Drop-outs in both groups
      occurred within the first 2 weeks. Paroxetine and CBT significantly decreased
      PTSD-symptoms (CAPS) as well as concurrent depression (MADRS) after 3 months
      treatment. At 6 month follow-up, symptoms of PTSD had slightly increased in the
      paroxetine group and further decreased in the cognitive-behavioural therapy
      group. (Int J Psych Clin Pract 2004; 8: 19-23). 

PMID- 24937580
TI  - Does having offspring reduce the risk of suicide in women?
AB  - OBJECTIVES: To assess the effect of having offspring, dependant offspring (<18
      years), non-dependant offspring (> 18 years) and no offspring on suicide rates in
      women. Also to ascertain whether the offspring living at home or away from home
      altered the outcome. METHODS: Sixty records held by the coroner of female
      suicides in Rotherham over a 10-year period (1991-2001) were studied. The 1991
      Census for South Yorkshire and the Office For National Statistics (England and
      Wales) provided comparative data for the general population. Data obtained for
      both groups included the age of the woman, number of children, age of children,
      whether the children lived with their mother or away from home. The results were
      subjected to chi-squared statistical analysis. RESULTS: There was no difference
      in the percentage of childless women when comparing the female suicide population
      of Rotherham with the general female population. However, females with offspring
      living at home regardless of age were significantly underrepresented in our
      sample (P < 0.001). CONCLUSION: The protective effect offspring confer on their
      mother against suicide appears to operate so long as the offspring lives at home
      irrespective of off spring's age. The protective effect appears to be lost once
      they leave home. These findings are discussed in the context of the kin selection
      hypothesis and deCatanzaro's Darwinian hypothesis on human suicide. (Int J Psych
      Clin Pract 2004; 8: 25-29).

PMID- 24937581
TI  - Oxcarbazepine: Efficacy, safety, and tolerability in the treatment of mania.
AB  - A twelve-week study examined the efficacy, safety, and tolerability of
      oxcarbazepine in the treatment of mania. Twenty male subjects, all of whom were
      stable on valproic acid, qualified for the study. The conversion from valproic
      acid to oxcarbazepine was completed over a three-week period. Scores from the
      BPRS, CGI and SAJEE-GI were collected and analyzed. The results of the study
      supported the efficacy, safety, and tolerability of oxcarbazepine for the
      treatment of mania. Another potential advantage of oxcarbazepine is a metabolic
      pathway that may reduce drug interactions. Qnt] Psych Can Pract 2004; 8: 37-40). 

PMID- 24937582
TI  - Antipsychotic drug use pattern for patients with schizophrenia in an outpatient
      clinic in Turkey: A retrospective study.
AB  - INTRODUCTION: Pharmacotherapy for schizophrenia is a dynamic process that can
      change over time. The goal of this study was to examine the pattern of
      antipsychotic drug (APD) use for patients with schizophrenia in an outpatient
      clinic. METHOD: We evaluated the medication use pattern in patients with
      schizophrenia treated with antipsychotic drugs in an outpatient clinic in a
      period of 4 years. Patients who used any antipsychotic medication stably for at
      least 6 months were included in the study in this period. Patients who had been
      noncompliant to the treatment or did not come to the clinic again were excluded.
      Patients' records were reviewed in respect to the use of APD as an initial
      treatment, the duration of a single or combined APD use, the changing of APD
      regimen, and adding of a new APD or other adjuvant drugs to APDs. RESULTS: A
      total of 152 patients diagnosed with schizophrenia were treated during the study
      period, of whom 60 (39.5%) maintained the treatment with compliance for at least
      6 months. Mean duration of the treatment was 15.8 (+10.7) months (range 6-48).
      The most commonly used antipsychotic drugs were atypical agents (in 68.3% of
      patients), and depot neuroleptics were used in the 46.7% of patients more often
      than any other antipsychotic drug at any time of the treatment. Two or more
      antipsychotic drugs were used at some time during this period in 24 patients
      (40.0%). Of all patients, 45.0% had their drug regimen changed: medication
      regimen was changed once in 28.3% patients and two to four times in 16.7%
      patients. The longer the duration of treatment, the more patients had their
      medication changed. Most added drugs were typical ones (16.7%). Of all patients,
      48 (80.0%) had used adjuvant drugs at any time during the treatment. There were
      no differences between the use of combined drug, medication changing and
      demographic variables of the patients. CONCLUSION: The results of this study
      support previous reports of the frequent use of atypical antipsychotic drugs,
      combination antipsychotic therapy, and adjuvant drugs in clinical practice.
      Medication switching is more common in the treatment of patients with
      schizophrenia. Prospective controlled trials are needed to determine whether
      combination antipsychotic therapy or switching medication regimen is clinically
      beneficial and to provide guidelines on when and for whom that should be
      considered. (Int J Psych Clin Pract 2004; 8: 41-45).

PMID- 24937583
TI  - An open-label clinical trial of milnacipran in fibromyalgia syndrome with co
      morbid depressive symptoms.
AB  - OBJECTIVE: To evaluate the efficacy of the serotonin and noradrenaline reuptake
      inhibiting antidepressant, milnacipran, in patients with fibromyalgia syndrome
      and co-morbid depression. METHODS: Twenty patients with fibromyalgia syndrome and
      co-morbid depressive symptoms were treated with the serotonin and noradrenaline
      reuptake inhibitor, milnacipran, in an open label study. The initial dose of
      milnacipran was 30 mg/day which could be increased as needed up to 100 mg/day.
      Patients were evaluated at baseline and after 4, 8 and 12 weeks of treatment.
      Pain level and global symptomatology were determined using visual analogue
      scales. Pain was also accessed by use of the face scale, while the severity of
      depression was determined using the Zung self-rating depression scale. RESULTS:
      Two patients withdrew because of persistent nausea. Pain and general
      symptomatology were significantly improved at the end of the study, with five
      patients having a reduction in pain of greater than 50%. Post-hoc analysis showed
      that the 11 patients who were no longer depressed at the end of the study had the
      greatest improvement in pain and overall FMS symptomatology. CONCLUSION: The data
      suggest that milnacipran may be effective in the treatment of FMS, especially
      when associated with depression. Qnt] Psych Clin Pract 2004; 8: 47-51).

PMID- 24937584
TI  - What is the usual length of stay in a psychiatric ward?
AB  - INTRODUCTION: Admission statistics can provide valuable data for planning and
      policy in the NHS. However, there has been little agreement about meaningful ways
      of summarising and expressing such data. We set out to (i) explore the
      distribution of length of inpatient stay and to examine the most appropriate
      measure of central tendency; and (ii) examine the relationship between severity
      of mental illness and length of stay. METHOD: Length of stay was recorded for a
      12-month cohort of psychiatric admissions to a district general hospital
      psychiatric unit. These data were compared with a previous cohort study and also
      with DoH statistics. RESULTS: Length of inpatient stay followed an exponential
      decay curve. The median length of stay for all three cohorts examined was
      approximately 15 days. Absence of serious mental illness was significantly
      associated with shorter length of stay. CONCLUSION: Length of stay is not
      normally distributed and so the median value is the preferred measure of central
      tendency. All cohorts examined showed a median value of around 15 days. Large
      numbers of patients are admitted for a week or less which has implications for
      inpatient and community services. Qnt] Psych Clin Pract 2004; 8: 53-56).

PMID- 24937585
TI  - Physical examination performed by psychiatrists.
AB  - Too little, too late? Physical examinations performed by trainee psychiatrists on
      newly admitted psychiatric patients. OBJECTIVES: To assess the comprehensiveness
      of the physical examination carried out by psychiatric trainees on acute in
      patient units. To quantify delays in undertaking physical examination on
      psychiatric inpatients. METHOD: A prospective case note study of 60 consecutive
      admissions to acute psychiatric wards in North Staffordshire. Information
      regarding demography, details of physical examination and routine blood
      investigations was collected. RESULTS: The case notes of 60 inpatients were
      studied. Mean age was 38.7 years and the sex ratio equal. A delay in performing a
      physical occurred in 17 (28.8%) patients. No explanation for a delay was given in
      six (10.0%) cases. The mean time to physical examination from admission was 61.8
      h (range 0-612 h). The standard of physical examination was variable. The central
      nervous system (CNS) was reported as 'grossly intact' in six (10.2%) cases with
      only 34 (57.6%) of patients having a comprehensive CNS examination. CONCLUSIONS:
      Psychiatric patients are not receiving a comprehensive physical examination.
      Whilst the patient's ability to co-operate may account for a delay in the
      examination, it is unlikely to be the reason for the CNS being examined in just
      half the patients. Opportunities to reduce the physical morbidity associated with
      mental illness may be being lost. (MJ Psych Clin Pract 2004; 8: 57-60).

PMID- 24937586
TI  - Major depression versus dysthymia: Comorbid psychiatric disorders, psychotropic
      medication patterns, and psychotherapy sessions.
AB  - The objective of this study was to examine, among those with major depression
      versus dysthymia, relationships with comorbid psychopathol-ogy, patterns of
      psychotropic medication prescription, and number of psychotherapy sessions
      utilized. Using a retrospective approach, a single investigator reviewed the
      medical records of individuals diagnosed with major depression or dysthymia
      (those with both disorders were excluded from analysis) in an adult, university
      based, outpatient psychiatry clinic. Records were examined for demographic
      information, Axis I and II diagnoses, number and type of psychotropic
      medications, and number of psychotherapy sessions. There were no demographic
      differences between groups. Compared to those with major depression, individuals
      with dysthymia had a similar number of Axis I diagnoses, but were significantly
      more likely to be diagnosed with a personality disorder. Those with major
      depression were prescribed a significantly greater number of psychotropic
      medications, and all seven patients who received antipsychotics were diagnosed
      with major depression. Finally, there were no between-group differences in the
      number of psychotherapy sessions. These data indicate that, compared with major
      depression, dysthymia may have significantly greater Axis II, but not Axis I,
      psychiatric comorbidity. The implications of greater psychotropic medication
      prescription among the subsample with major depression, and similar psychotherapy
      utilization between groups, is discussed. Qnt] Psych Clin Pract 2004; 8: 61-63). 

PMID- 24937587
TI  - Psychotherapy and counselling in practice, a narrative framework.

PMID- 24937588
TI  - Wine: a scientific exploration.

PMID- 24937589
TI  - MCQs in Psychiatry.

PMID- 24937590
TI  - Presumed curable: an illustrated casebook of victorian psychiatric patients in
      bethlem hospital.

PMID- 24937592
TI  - Nerve growth factor promotes killing of Leishmania donovani by macrophages
      through the induction of hydrogen peroxide.
AB  - Visceral leishmaniasis is protozoonosis that occurs worldwide and still requires
      effective therapies with less toxicity. In this study, we examined the
      antileishmanial effect of nerve growth factor (NGF) using a murine infection
      model. NGF blocked the infection of macrophages by Leishmania donovani, which was
      completely cancelled by a hydrogen peroxide inhibitor. In vivo, not only did NGF
      show antileishmanial effects, but combination therapy of NGF and sodium
      stibogluconate synergistically exhibited the activity more potently than each
      monotherapy. These results indicate that NGF exerts antileishmanial effect by
      stimulating hydrogen peroxide production in macrophages and can be a novel
      therapy for leishmaniasis.

PMID- 24937591
TI  - Microvescicles derived from mesenchymal stromal cells are not as effective as
      their cellular counterpart in the ability to modulate immune responses in vitro.
AB  - Mesenchymal stromal cells (MSCs) are multipotent cells that possess broad
      immunomodulatory properties; the mechanisms underlying these properties have not
      been completely clarified. Aim of this study was to compare in vitro
      immunomodulatory effects of MSCs with those of microvesicles (MVs) released in
      supernatants from the same MSCs. MSCs were generated from bone marrow of 12
      healthy donors (HDs) and MVs were isolated from their supernatant by serial
      ultracentrifugation according to two different procedures. Both MSCs and MVs were
      characterized by flow cytometry and incubated in vitro with peripheral blood
      mononuclear cells (PBMCs) of 12 HDs after stimulation with PHA and CpG. Growth
      factors and cytokines were quantified by ELISA. MVs were identified as 0.1-1 MUm
      particles positive for CMFDA, CD107, and CD13. MSCs were significantly more
      capable to inhibit in vitro PHA-induced T-cell proliferation as compared with the
      corresponding MVs (P<0.01 and P<0.05 for MSC:PBMC ratio 1:2 and 1:10,
      respectively). While MVs displayed similar inhibitory activity on B-cell
      proliferation (P=0.43 as compared with PBMCs/CpG/MSCs; MSC:PBMC ratio 1:10) they
      induced lower inhibitory effect on plasmacell differentiation and antibody
      secretion (P<0.05 as compared with PBMCs/CpG/MSCs). For both T and B cells, MSC
      co-colture induced a statistically significant increase in IL-10 and TGFbeta and
      decrease of GM-CSF and IFNgamma, as compared with MV incubation. Our data
      indicate a lower in vitro immunomodulatory effect of MVs on T-cell proliferation
      and antibody formation, as compared with their cellular counterpart. The relative
      clinical benefit of either MSCs or MVs needs to be compared in proper prospective
      studies.

PMID- 24937594
TI  - Distal posterior inferior cerebellar artery aneurysms: clinical features and
      outcome of 80 patients.
AB  - OBJECTIVE: Aneurysms of the posterior inferior cerebellar artery (PICA) distal to
      its origin are rare. Beside their rarity, their treatment is challenged by a high
      proportion of fusiform aneurysms, torturous course of PICA, and often severe
      bleeding. Our aim is to represent the characteristics of these aneurysms and
      their treatment, as well as to analyze outcome. METHODS: We reviewed
      retrospectively 80 patients with PICA aneurysms who were treated at the
      Department of Neurosurgery, Helsinki, Finland. RESULTS: The 80 patients had
      altogether 91 distal PICA aneurysms. Subarachnoid hemorrhage occurred in 74
      (93%), and the distal PICA aneurysm was ruptured in 68 (85%). Compared with
      aneurysms at other locations, distal PICA aneurysms were smaller, more often
      fusiform, and more often caused an intraventricular hemorrhage as well as
      rebleeding. Modified surgical techniques (trapping, wrapping, proximal occlusion,
      resection, coagulation) were used in 10 (32%) fusiform and in 3 (6%) saccular
      aneurysms. Revascularization was needed in 3 (4%) cases. One aneurysm was
      primarily embolized. Within a year after aneurysm diagnosis, 18 patients had
      died. Among survivors, most returned to independent or previous state of living:
      52 (91%); only 1 patient was unable to return home. CONCLUSIONS: Microsurgery is
      a feasible treatment for distal PICA aneurysms. Despite the challenge of often
      severe hemorrhage, wide-necked aneurysms, and some risk for laryngeal palsy, most
      patients surviving the initial stage return to normal life. Because of the
      greater number of rebleedings than for aneurysms at other locations, immediate
      treatment is crucial.

PMID- 24937593
TI  - A var gene upstream element controls protein synthesis at the level of
      translation initiation in Plasmodium falciparum.
AB  - Clonally variant protein expression in the malaria parasite Plasmodium falciparum
      generates phenotypic variability and allows isogenic populations to adapt to
      environmental changes encountered during blood stage infection. The underlying
      regulatory mechanisms are best studied for the major virulence factor P.
      falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is encoded by the
      multicopy var gene family and only a single variant is expressed in individual
      parasites, a concept known as mutual exclusion or singular gene choice. var gene
      activation occurs in situ and is achieved through the escape of one locus from
      epigenetic silencing. Singular gene choice is controlled at the level of
      transcription initiation and var 5' upstream (ups) sequences harbour regulatory
      information essential for mutually exclusive transcription as well as for the
      trans-generational inheritance of the var activity profile. An additional level
      of control has recently been identified for the var2csa gene, where an mRNA
      element in the 5' untranslated region (5' UTR) is involved in the reversible
      inhibition of translation of var2csa transcripts. Here, we extend the knowledge
      on post-transcriptional var gene regulation to the common upsC type. We
      identified a 5' UTR sequence that inhibits translation of upsC-derived mRNAs.
      Importantly, this 5' UTR element efficiently inhibits translation even in the
      context of a heterologous upstream region. Further, we found var 5' UTRs to be
      significantly enriched in uAUGs which are known to impair the efficiency of
      protein translation in other eukaryotes. Our findings suggest that regulation at
      the post-transcriptional level is a common feature in the control of PfEMP1
      expression in P. falciparum. 

PMID- 24937595
TI  - Clinical factors predicting outcomes after surgical resection for sporadic
      cerebellar hemangioblastomas.
AB  - OBJECTIVE: To determine whether various clinical factors are related to long-term
      outcomes of patients with sporadic cerebellar hemangioblastomas. METHODS:
      Subjects included 36 patients (19 men and 17 women) who underwent resection of
      sporadic hemangioblastoma in the cerebellum. Age at surgery ranged from 17-79
      years (mean, 49.7 years). The tumor size, which was defined as the largest
      diameter of the lesion including the extratumoral cyst, ranged from 10-67 mm
      (mean, 36.4 mm). Obstructive hydrocephalus secondary to mass effect on the fourth
      ventricle was present in 21 (58.3%) patients preoperatively. RESULTS: Total tumor
      removal was achieved in 31 of 36 patients (86%). In 4 (11%) patients with solid
      tumors, postoperative hematoma occurred in the removal cavity, and hematoma
      removal was required immediately after surgery. We followed 30 patients for >12
      months after the initial surgery (mean, 72.9 months; range, 12-274 months).
      Recurrence of hemangioblastoma developed in 4 of 30 patients (13%) at 6 months,
      17 months, 6 years, and 22 years after surgery. At the final follow-up
      examination, 9 (30%) of 30 patients showed some residual neurologic symptoms
      (poor group), whereas the remaining 21 patients showed no deficits (good group).
      Using univariate analysis, both age at surgery and tumor characteristics (cystic
      or solid) were significantly related to long-term patient outcomes (P < 0.05).
      However, in a multiple logistic regression analysis, only tumor characteristics
      were correlated with outcomes (P = 0.017). At the final follow-up examination,
      patients with solid tumors more frequently showed poor outcomes than patients
      with cystic tumors. CONCLUSIONS: The solid configuration observed on preoperative
      images of sporadic cerebellar hemangioblastomas is one of the most important
      clinical factors related to both immediate and long-term outcomes after surgery.

PMID- 24937596
TI  - Biomechanical analysis of disc pressure and facet contact force after simulated
      two-level cervical surgeries (fusion and arthroplasty) and hybrid surgery.
AB  - OBJECTIVE: The objective of this study was designed to compare 2-level cervical
      disc surgery (2-level anterior cervical discectomy and fusion [ACDF] or disc
      arthroplasty) and hybrid surgery (ACDF/arthroplasty) in terms of postoperative
      adjacent-level intradiscal pressure (IDP) and facet contact force (FCF). METHODS:
      Twenty-four cadaveric cervical spines (C3-T2) were tested in various modes,
      including extension, flexion, and bilateral axial rotation, to compare adjacent
      level IDP and FCF after specified treatments as follows: 1) C5-C6 arthroplasty
      using ProDisc-C (Synthes Spine, West Chester, Pennsylvania, USA) and C6-C7 ACDF,
      2) C5-C6 ACDF and C6-C7 arthroplasty using ProDisc-C, 3) 2-level C5-C6/C6-C7 disc
      arthroplasties, and 4) 2-level C5-C6/C6-C7 ACDF. IDPs were recorded at anterior,
      central, and posterior disc portions. RESULTS: After 2-level cervical arthrodesis
      (ACDF), IDP increased significantly at the anterior annulus of distal adjacent
      level disc during flexion and axial rotation and at the center of proximal
      adjacent-level disc during flexion. In contrast, after cervical specified
      treatments, including disc arthroplasty (2-level disc arthroplasties and hybrid
      surgery), IDP decreased significantly at the anterior annulus of distal adjacent
      level disc during flexion and extension and was unchanged at the center of
      proximal adjacent-level disc during flexion. Two-level cervical arthrodesis also
      tended to adversely impact facet loads, increasing distal rather than proximal
      adjacent-level FCF. CONCLUSION: Both hybrid surgery and 2-level arthroplasties
      seem to offer significant advantages over 2-level arthrodesis by reducing IDP at
      adjacent levels and approximating FCF of an intact spine. These findings suggest
      that cervical arthroplasties and hybrid surgery are an alternative to reduce IDP
      and facet loads at adjacent levels.

PMID- 24937597
TI  - Intraventricular craniopharyngiomas: surgical management and outcome analyses in
      24 cases.
AB  - OBJECTIVE: Pure intraventricular craniopharyngioma is a rare subtype of
      craniopharyngioma that attaches frequently to the hypothalamus. The main
      challenge in tumor removal is protection of hypothalamic structure. The aim of
      our study was to set up a feasible risk-evaluation approach to help the surgeons
      make an individual treatment plan. METHODS: We reviewed retrospectively 24
      patients with pure intraventricular craniopharyngioma who underwent surgical
      therapy. Third ventricular deformation and thalamic attachment of the tumor were
      assessed by preoperative magnetic resonance imaging and intraoperative
      inspection. Correlations between the outcome, extent of removal, and different
      attachment grades were analyzed. RESULTS: Preoperative magnetic resonance imaging
      grade had a significant correlation with functional outcome. Attachment grade was
      significantly correlated with endocrine, functional, and radiologic outcome. In
      the gross total removal (GTR) group, significantly more newly developed
      endocrinologic deficits were observed compared with patients who underwent
      subtotal removal (STR). All 6 GTR cases with the greatest attachment grade (grade
      2) acquired newly developed endocrine insufficiency. CONCLUSIONS: Attachment and
      deformation grade evaluated based on our criteria are significantly correlated
      with postoperative outcome. GTR of tightly attached tumor is associated with
      worse endocrinologic, functional, and radiologic outcomes compared with STR.
      Hence, we suggest that individual surgical plans should be made according to the
      grade of tumor attachment and hypothalamic deformation. STR should used in tumors
      with a high grade to achieve a good long-term outcome and avoid severe
      postoperative sequelae.

PMID- 24937598
TI  - Spinal instrumentation in patients with primary spinal infections does not lead
      to greater recurrent infection rates: an analysis of 118 cases.
AB  - OBJECTIVE: We sought to compare outcomes between patients undergoing
      decompression only versus decompression and instrumented fusion for primary
      spinal infections. METHODS: Records of patients with a diagnosis of primary
      spinal infection who underwent surgical management at our institution during a 10
      year period were reviewed. Patients were divided into 2 cohorts based on
      treatment received (decompression alone vs. decompression and instrumentation).
      Our primary end points were complication rates, need for reoperation, recurrent
      infections, and resolution of symptom(s) at last follow-up. RESULTS: A total of
      118 patients underwent surgical management for primary spinal infections. Thirty
      five patients presented with a cervical spine infection, 40 with a thoracic
      infection, and 43 with a lumbosacral infection. The mean age at presentation was
      57.1 +/- 13.5 years. Thirty-six patients underwent only decompression, and 82
      underwent decompression and instrumented fusion. In the decompression-only group,
      8.33% of patients had continued osteomyelitis/discitis compared with 9.76% of
      patients in the instrumented group (P = 0.807). Importantly, the reoperation rate
      was also similar between the decompression-only group (19.44%) and the
      instrumented group (17.07%; P = 0.756). Similarly, subanalyses based on infection
      location revealed no significant increase in rates of recurrent infection or
      reoperation in patients who underwent instrumentation. CONCLUSION: Patients who
      received just decompression for spinal infection had similar reoperation and
      continued infection rates as patients who additionally underwent instrumentation,
      irrespective of infection location within the spine. These findings suggest that
      instrumentation of the infected spine may be a safe treatment modality and should
      be considered when the spinal integrity is compromised.

PMID- 24937599
TI  - Endoscopic resection of a giant intradural retroclival ecchordosis physaliphora:
      surgical technique and literature review.
AB  - OBJECTIVE: To report the first complete resection of a giant ecchordosis
      physaliphora using an endoscopic transclival approach and to provide a current
      review of the literature. METHODS: This rare benign lesion, originating from
      embryonic notochordal remnants, was located in the prepontine cistern of a 63
      year-old man presenting with progressive tremor and imbalance. Preoperative
      imaging demonstrated a 2.1-cm intradural lesion abutting the pons and basilar
      artery and extending through the dura mater. RESULTS: A gross total resection was
      successfully achieved endoscopically without neurovascular compromise or
      additional complications. Postoperative histopathologic examination was
      consistent with a diagnosis of giant ecchordosis physaliphora. CONCLUSIONS: An
      endoscopic endonasal transclival approach provided a direct, minimally invasive
      route for safe and complete resection of this rare prepontine tumor, as it has
      for similarly located skull base chordomas. Our experience highlights the utility
      of endoscopy in visualization of both pathologic entities and nearby critical
      neurovascular structures in the management of ecchordosis physaliphora and other
      cranial base neoplasms.

PMID- 24937600
TI  - Aneurysms associated with arteriovenous malformations: classification and risk
      estimation.

PMID- 24937601
TI  - Cerebellomedullary fissure dissection and tonsillar mobilization: a gateway to
      lesions around the medulla.

PMID- 24937603
TI  - High-mobility group box 1 (HMGB1) impaired cardiac excitation-contraction
      coupling by enhancing the sarcoplasmic reticulum (SR) Ca(2+) leak through TLR4
      ROS signaling in cardiomyocytes.
AB  - High-mobility group box 1 (HMGB1) is a proinflammatory mediator playing an
      important role in the pathogenesis of cardiac dysfunction in many diseases. In
      this study, we explored the effects of HMGB1 on Ca(2+) handling and cellular
      contractility in cardiomyocytes to seek for the mechanisms underlying HMGB1
      induced cardiac dysfunction. Our results show that HMGB1 increased the frequency
      of Ca(2+) sparks, reduced the sarcoplasmic reticulum (SR) Ca(2+) content, and
      decreased the amplitude of systolic Ca(2+) transient and myocyte contractility in
      dose-dependent manners in adult rat ventricular myocytes. Inhibiting high
      frequent Ca(2+) sparks with tetracaine largely inhibited the alterations of SR
      load and Ca(2+) transient. Blocking Toll-like receptor 4 (TLR4) with TAK-242 or
      knockdown of TLR4 by RNA interference remarkably inhibited HMGB1 induced high
      frequent Ca(2+) sparks and restored the SR Ca(2+) content. Concomitantly, the
      amplitude of systolic Ca(2+) transient and myocyte contractility had
      significantly increased. Furthermore, HMGB1 increased the level of intracellular
      reactive oxygen species (ROS) and consequently enhanced oxidative stress and
      CaMKII-activated phosphorylation (pSer2814) in ryanodine receptor 2 (RyR2). TAK
      242 pretreatment significantly decreased intracellular ROS levels and oxidative
      stress and hyperphosphorylation in RyR2, similar to the effects of antioxidant
      MnTBAP. Consistently, MnTBAP normalized HMGB1-impaired Ca(2+) handling and
      myocyte contractility. Taken together, our findings suggest that HMGB1 enhances
      Ca(2+) spark-mediated SR Ca(2+) leak through TLR4-ROS signaling pathway, which
      causes partial depletion of SR Ca(2+) content and hence decreases systolic Ca(2+)
      transient and myocyte contractility. Prevention of SR Ca(2+) leak may be an
      effective therapeutic strategy for the treatment of cardiac dysfunction related
      to HMGB1 overproduction. 

PMID- 24937602
TI  - Controlling osteogenic stem cell differentiation via soft bioinspired hydrogels.
AB  - Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is guided by
      various physical and biochemical factors. Among these factors, modulus (i.e.,
      rigidiy) of the ECM has gained significant attention as a physical osteoinductive
      signal that can contribute to endochondral ossification of a cartilaginous
      skeletal template. However, MSCs also participate in intramembranous bone
      formation, which occurs de novo from within or on a more compliant tissue
      environment. To further understand the role of the matrix interactions in this
      process, we evaluated osteogenic differentiation of hMSCs cultured on low moduli
      (102, 390 or 970 Pa) poly(N-isopropylacrylamide) (p(NIPAAm)) based semi
      interpenetrating networks (sIPN) modified with the integrin engaging peptide bsp
      RGD(15) (0, 105 or 210 uM). Cell adhesion, proliferation, and osteogenic
      differentiation of hMSCs, as measured by alkaline phosphatase (ALP), runt-related
      transcription factor 2 (RUNX2), bone sialoprotein-2 (iBSP), and osteocalcien
      (OCN) protein expression, was highest on substrates with the highest modulus and
      peptide concentrations. However, within this range of substrate stiffness, many
      osteogenic cellular functions were enhanced by increasing either the modulus or
      the peptide density. These findings suggest that within a compliant and low
      modulus substrate, a high affinity adhesive ligand serves as a substitute for a
      rigid matrix to foster osteogenic differentiation. 

PMID- 24937605
TI  - Hydrolytic enzymes conjugated to quantum dots mostly retain whole catalytic
      activity.
AB  - BACKGROUND: Tagging a luminescent quantum dot (QD) with a biological like enzyme
      (Enz) creates value-added entities like quantum dot-enzyme bioconjugates
      (QDEnzBio) that find utility as sensors to detect glucose or beacons to track
      enzymes in vivo. For such applications, it is imperative that the enzyme remains
      catalytically active while the quantum dot is luminescent in the bioconjugate. A
      critical feature that dictates this is the quantum dot-enzyme linkage chemistry.
      Previously such linkages have put constraints on polypeptide chain dynamics or
      hindered substrate diffusion to active site, seriously undermining enzyme
      catalytic activity. In this work we address this issue using avidin-biotin
      linkage chemistry together with a flexible spacer to conjugate enzyme to quantum
      dot. METHODS: The catalytic activity of three biotinylated hydrolytic enzymes,
      namely, hen egg white lysozyme (HEWL), alkaline phosphatase (ALP) and
      acetylcholinesterase (AChE) was investigated post-conjugation to streptavidin
      linked quantum dot for multiple substrate concentrations and varying degrees of
      biotinylation. RESULTS: We demonstrate that all enzymes retain full catalytic
      activity in the quantum dot-enzyme bioconjugates in comparison to biotinylated
      enzyme alone. However, unlike alkaline phosphatase and acetylcholinesterase, the
      catalytic activity of hen egg white lysozyme was observed to be increasingly
      susceptible to ionic strength of medium with rising level of biotinylation. This
      susceptibility was attributed to arise from depletion of positive charge from
      lysine amino groups after biotinylation. CONCLUSIONS: We reasoned that avidin
      biotin linkage in the presence of a flexible seven atom spacer between biotin and
      enzyme poses no constraints to enzyme structure/dynamics enabling retention of
      full enzyme activity. GENERAL SIGNIFICANCE: Overall our results demonstrate for
      the first time that streptavidin-biotin chemistry can yield quantum dot enzyme
      bioconjugates that retain full catalytic activity as native enzyme.

PMID- 24937606
TI  - Investigation of thorium salts as candidate materials for direct observation of
      the (229m)Th nuclear transition.
AB  - Recent efforts to measure the (229m)Th -> (229g)Th nuclear transition sparked
      interest in understanding the electronic structure of wide-gap thorium salts.
      Such materials could be used to measure this nuclear transition using optical
      spectroscopy in solid-state devices. Here, we present screened hybrid density
      functional theory and many-body G0W0 calculations of two candidate materials,
      namely, Na2ThF6 and ThF4, for such a measurement. Our results show an electronic
      gap larger than 10 eV for both materials, suggesting that the internal conversion
      nuclear de-excitation channel would be suppressed in these materials. We also
      present results for ThX4 (X = Cl, Br, I), materials with smaller gaps
      significantly easier to access experimentally. 

PMID- 24937604
TI  - Dysregulation of cardiolipin biosynthesis in pediatric heart failure.
AB  - Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is
      critical for optimal mitochondrial function. CL abnormalities have been
      demonstrated in the failing rodent and adult human heart. The aim of this study
      was to determine whether abnormalities in CL content and the CL biosynthesis and
      remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy
      (IDC). A cross-sectional analysis of myocardial tissue from 119 IDC and non
      failing (NF) control samples was performed. Electrospray ionizing mass
      spectrometry was used to measure total CL and CL species content in LV tissue. RT
      PCR was employed to measure gene expression of the enzymes in the CL biosynthesis
      and remodeling pathways in both the adult and pediatric heart. Significantly
      lower total and (18:2)4CL (the beneficial species) content was demonstrated in
      myocardium from pediatric patients with IDC compared to NF controls. Analysis of
      mitochondrial gene transcripts was used to demonstrate that there is no decrease
      in mitochondrial content. Expression of two biosynthesis enzymes and one
      remodeling enzyme was significantly lower in pediatric IDC compared to NF
      controls. Expression of two phospholipases involved in CL degradation were also
      altered, one up- and one down-regulated. Except for one remodeling enzyme, these
      changes are unique from those in the failing adult heart. Similar to what has
      been seen in adults and in a rat model of IDC, total and (18:2)4CL are lower in
      pediatric IDC. Unique CL species profiles are seen in heart tissue from children
      with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme
      expression likely explain the differences in CL profiles observed in IDC and
      implicate unique age-related mechanisms of disease. 

PMID- 24937608
TI  - Supporting family caregivers.

PMID- 24937611
TI  - Promoting patient dignity in nursing care.

PMID- 24937612
TI  - Sleepless in stepdown.

PMID- 24937613
TI  - Exploring how nurses and managers perceive shared governance.
AB  - BACKGROUND: Nurse managers have a pivotal role in the success of unit-based
      councils, which include direct care nurses. These councils establish shared
      governance to provide innovative, quality-based, and cost-effective nursing care.
      PURPOSE: This study explored differences between direct care nurses' and nurse
      managers' perceptions of factors affecting direct care nurses' participation in
      unit-based and general shared governance activities and nurse engagement.
      METHODS: In a survey research study, 425 direct care RNs and nurse managers were
      asked to complete a 26-item research survey addressing 16 shared governance
      factors; 144 participated (response rate = 33.8%). RESULTS: Most nurse
      participants provided direct care (N = 129, 89.6%; nurse managers = 15, 10.4%),
      were older than 35 (75.6%), had more than 5 years of experience (76.4%), and
      worked more than 35 hours per week (72.9%). Direct care nurses' and managers'
      perceptions showed a few significant differences. Factors ranked as very
      important by direct care nurses and managers included direct care nurses
      perceiving support from unit manager to participate in shared governance
      activities (84.0%); unit nurses working as a team (79.0%); direct care nurses
      participating in shared governance activities won't disrupt patient care (76.9%);
      and direct care nurses will be paid for participating beyond scheduled shifts
      (71.3%). Overall, 79.2% had some level of engagement in shared governance
      activities. Managers reported more engagement than direct care nurses.
      CONCLUSIONS: Nurse managers and unit-based councils should evaluate nurses'
      perceptions of manager support, teamwork, lack of disruption to patient care, and
      payment for participation in shared governance-related activities. These research
      findings can be used to evaluate hospital practices for direct care nurse
      participation in unit-based shared governance activities.

PMID- 24937616
TI  - Severe sunburn.

PMID- 24937618
TI  - What nursing taught us.

PMID- 24937619
TI  - How to energize your staff meetings.

PMID- 24937620
TI  - Take aim at acute kidney injury with RIFLE criteria.

PMID- 24937621
TI  - What's the buzz about medical-grade honey?

PMID- 24937623
TI  - Patient falls: searching for the elusive "silver bullet".

PMID- 24937624
TI  - Managing the pain of diabetic peripheral neuropathy.

PMID- 24937625
TI  - Infusion therapy: much more than a simple task.

PMID- 24937626
TI  - Obtaining a wound swab culture specimen.

PMID- 24937628
TI  - Limitations to the cultural ratchet effect in young children.
AB  - Although many animal species show at least some evidence of cultural
      transmission, broadly defined, only humans show clear evidence of cumulative
      culture. In the current study, we investigated whether young children show the
      "ratchet effect," an important component of cumulative culture--the ability to
      accumulate efficient modifications across generations. We tested 16 diffusion
      chains--altogether consisting of 80 children--to see how they solved an
      instrumental task (i.e., carrying something from one location to another). We
      found that when the chain was seeded with an inefficient way of solving the task,
      4-year-olds were able to innovate and transmit these innovations so as to reach a
      more efficient solution. However, when it started out with relatively efficient
      solutions already (i.e., the ones that children in a control condition discovered
      for themselves), there were no further techniques invented and/or transmitted
      beyond that. Thus, young children showed the ratchet effect to a limited extent,
      accumulating efficient modifications but not going beyond the inventive level of
      the individual.

PMID- 24937629
TI  - Category-specific face prototypes are emerging, but not yet mature, in 5-year-old
      children.
AB  - Adults' expertise in face recognition has been attributed to norm-based coding.
      Moreover, adults possess separable norms for a variety of face categories (e.g.,
      race, sex, age) that appear to enhance recognition by reducing redundancy in the
      information shared by faces and ensuring that only relevant dimensions are used
      to encode faces from a given category. Although 5-year-old children process own
      race faces using norm-based coding, little is known about the organization and
      refinement of their face space. The current study investigated whether 5-year
      olds rely on category-specific norms and whether experience facilitates the
      development of dissociable face prototypes. In Experiment 1, we examined whether
      Chinese 5-year-olds show race-contingent opposing aftereffects and the extent to
      which aftereffects transfer across face race among Caucasian and Chinese 5-year
      olds. Both participant races showed partial transfer of aftereffects across face
      race; however, there was no evidence for race-contingent opposing aftereffects.
      To examine whether experience facilitates the development of category-specific
      prototypes, we investigated whether race-contingent aftereffects are present
      among Caucasian 5-year-olds with abundant exposure to Chinese faces (Experiment
      2) and then tested separate groups of 5-year-olds with two other categories with
      which they have considerable experience: sex (male/female faces) and age
      (adult/child faces) (Experiment 3). Across all three categories, 5-year-olds
      showed no category-contingent opposing aftereffects. These results demonstrate
      that 5 years of age is a stage characterized by minimal separation in the norms
      and associated coding dimensions used for faces from different categories and
      suggest that refinement of the mechanisms that underlie expert face processing
      occurs throughout childhood.

PMID- 24937630
TI  - Using animal performance data to evidence the under-reporting of case herds
      during an epizootic: application to an outbreak of bluetongue in cattle.
AB  - Following the emergence of the Bluetongue virus serotype 8 (BTV-8) in France in
      2006, a surveillance system (both passive and active) was implemented to detect
      and follow precociously the progression of the epizootic wave. This system did
      not allow a precise estimation of the extent of the epizootic. Infection by BTV-8
      is associated with a decrease of fertility. The objective of this study was to
      evaluate whether a decrease in fertility can be used to evidence the under
      reporting of cases during an epizootic and to quantify to what extent non
      reported cases contribute to the total burden of the epizootic. The cow fertility
      in herds in the outbreak area (reported or not) was monitored around the date of
      clinical signs. A geostatistical interpolation method was used to estimate a date
      of clinical signs for non-reported herds. This interpolation was based on the
      spatiotemporal dynamic of confirmed case herds reported in 2007. Decreases in
      fertility were evidenced for both types of herds around the date of clinical
      signs. In non-reported herds, the decrease fertility was large (60% of the effect
      in reported herds), suggesting that some of these herds have been infected by the
      virus during 2007. Production losses in non-reported infected herds could thus
      contribute to an important part of the total burden of the epizootic. Overall,
      results indicate that performance data can be used to evidence the under
      reporting during an epizootic. This approach could be generalized to pathogens
      that affect cattle's performance, including zoonotic agents such as Coxiella
      burnetii or Rift Valley fever virus. 

PMID- 24937631
TI  - Increased protein kinase C gamma activity induces Purkinje cell pathology in a
      mouse model of spinocerebellar ataxia 14.
AB  - Spinocerebellar ataxias (SCAs) are hereditary diseases leading to Purkinje cell
      degeneration and cerebellar dysfunction. Most forms of SCA are caused by
      expansion of CAG repeats similar to other polyglutamine disorders such as
      Huntington's disease. In contrast, in the autosomal dominant SCA-14 the disease
      is caused by mutations in the protein kinase C gamma (PKCgamma) gene which is a
      well characterized signaling molecule in cerebellar Purkinje cells. The study of
      SCA-14, therefore, offers the unique opportunity to reveal the molecular and
      pathological mechanism eventually leading to Purkinje cell dysfunction and
      degeneration. We have created a mouse model of SCA-14 in which PKCgamma protein
      with a mutation found in SCA-14 is specifically expressed in cerebellar Purkinje
      cells. We find that in mice expressing the mutated PKCgamma protein the
      morphology of Purkinje cells in cerebellar slice cultures is drastically altered
      and mimics closely the morphology seen after pharmacological PKC activation.
      Similar morphological abnormalities were seen in localized areas of the
      cerebellum of juvenile transgenic mice in vivo. In adult transgenic mice there is
      evidence for some localized loss of Purkinje cells but there is no overall
      cerebellar atrophy. Transgenic mice show a mild cerebellar ataxia revealed by
      testing on the rotarod and on the walking beam. Our findings provide evidence for
      both an increased PKCgamma activity in Purkinje cells in vivo and for
      pathological changes typical for cerebellar disease thus linking the increased
      and dysregulated activity of PKCgamma tightly to the development of cerebellar
      disease in SCA-14 and possibly also in other forms of SCA. 

PMID- 24937633
TI  - Erlotinib Salvage Therapy in Pulmonary Adenocarcinoma Patients With Disease
      Progression After Previous EGFR-TKI Treatment.
AB  - BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor (TKI) with promising efficacy in treating pulmonary
      adenocarcinoma. Treatment choices are few when patients with pulmonary
      adenocarcinoma have failed both EGFR-TKI and chemotherapy. The purpose of this
      study was to demonstrate the efficacy of erlotinib as salvage treatment for these
      nonresponsive patients. METHODS: We retrospectively reviewed the chart records of
      our stage IV pulmonary adenocarcinoma patients who were diagnosed and treated
      between July 2004 and June 2013. Clinical data, including type of response to
      treatment, time to disease progression, duration between the end of first-line
      EGFR-TKI treatment and starting erlotinib treatment, and overall survival time,
      were collected. RESULTS: A total of 98 patients were enrolled, and all had been
      treated with EGFR-TKI, either as a first-line therapy or following platinum-based
      chemotherapy; of them, 60 patients had a response to initial EGFR-TKI treatment.
      All received erlotinib as salvage treatment after their disease had progressed
      following EGFR-TKI treatment. Ninety-three (93.3%) patients had also received
      previous platinum-based chemotherapy. The median progression-free survival with
      erlotinib as salvage treatment for patients with and without a response to front
      line EGFR-TKI was 4.9 and 3.4 months (P=0.869), respectively. The progression
      free survival with erlotinib treatment in the sensitizing EGFR mutation group was
      4.3 months, and in the EGFR wild-type group it was 2.6 months (P=0.22).
      CONCLUSIONS: In pulmonary adenocarcinoma patients who had been heavily treated,
      erlotinib could still be a choice, regardless of the EGFR mutation status, or
      whether the patients had responded to previous EGFR-TKI treatment.

PMID- 24937632
TI  - The medicalization of love.
AB  - Pharmaceuticals or other emerging technologies could be used to enhance (or
      diminish) feelings of lust, attraction, and attachment in adult romantic
      partnerships. Although such interventions could conceivably be used to promote
      individual (and couple) well-being, their widespread development and/or adoption
      might lead to the 'medicalization' of human love and heartache--for some, a
      source of a serious concern. In this essay, we argue that the medicalization of
      love need not necessarily be problematic, on balance, but could plausibly be
      expected to have either good or bad consequences depending upon how it unfolds.
      By anticipating some of the specific ways in which these technologies could yield
      unwanted outcomes, bioethicists and others can help to direct the course of
      love's medicalization--should it happen to occur--more toward the 'good' side
      than the 'bad.'

PMID- 24937634
TI  - Long-term Outcomes Following Radiotherapy for Adolescent Patients With
      Nonmetastatic WHO Type III Nasopharyngeal Carcinoma.
AB  - OBJECTIVES: To report long-term results of primary radiotherapy for
      nasopharyngeal cancer (NPC) presenting in the adolescent group. METHODS: Ten
      adolescent patients with World Health Organization (WHO) type III NPC were
      treated with primary radiotherapy at our institution between 1969 and 2007.
      Median age was 16.5 years (range, 11 to 21). Median radiotherapy dose to the
      primary target volume was 67.5 Gy (range, 60 to 74.8). The bilateral neck
      received 51.1 Gy (range, 50 to 60 Gy). Five patients were treated with once-daily
      radiotherapy and 5 received twice-daily radiotherapy. Three patients received
      neoadjuvant cisplatin and 5FU, and 1 patient received adjuvant maintenance
      cisplatin and 5FU. RESULTS: Median follow-up time was 9.5 years (range, 1.94 to
      34.74). Fifteen-year overall survival, cause-specific survival, and progression
      free survival rates were all 70%. Fifteen-year local and regional control rates
      were 100% and 90%. One patient recurred regionally and distantly simultaneously,
      and 2 patients developed distant metastases alone. All 3 died of their disease
      within 3 years. One patient died from multiple radiation-induced secondary
      meningiomas 34 years after radiotherapy. Five patients developed hypothyroidism,
      3 developed sensorineural hearing loss, and 4 developed dental complications. The
      overall rates of CTCAE grade 3, 4, and 5 toxicity were 40%, 10%, and 10%,
      respectively. Despite high-radiation doses to the skull base, none of the
      patients in this study developed grade 3+ cognitive or vision toxicity.
      CONCLUSIONS: Radiotherapy achieves excellent local control in adolescent patients
      with unresectable WHO type III NPC. Our data support current protocols to
      systematically tailor treatment volumes and deescalate radiation doses to reduce
      treatment toxicity.

PMID- 24937635
TI  - Analysis of Prognostic Factors Affecting the Outcome of Stage IB-IIB Cervical
      Cancer Treated by Radical Hysterectomy and Pelvic Lymphadenectomy.
AB  - OBJECTIVES: The aim of this study was to identify the risk factors predicting the
      prognosis of patients with early-stage cervical cancer and to evaluate the effect
      of adjuvant therapy in patients with certain risk factors. METHODS: The study
      population consisted of 274 patients who were presented with FIGO stage IB-IIB
      cervical cancers. They all received radical hysterectomy (type III) and
      systematic pelvic lymphadenectomy in our institute. Of the patients, 188 received
      postoperative adjuvant therapy including radiotherapy, chemotherapy, and
      chemotherapy plus radiotherapy. Radiotherapy was performed with a total of 50 Gy
      of external whole pelvic irradiation. Remote after loading of intravaginal
      iridium-192 brachytherapy were placed 1 to 2 weeks after completion of external
      RT. Chemotherapy was operated with 4 to 6 courses of platinum-based treatment.
      Chemotherapy plus radiotherapy was performed with the combination of periodically
      sequential chemotherapy and radiotherapy. RESULTS: Univariate analysis revealed
      clinical stage, parametrial invasion, and pelvic node metastasis affected
      patients' disease-free (DFS) and overall survival (OS) rates, whereas
      multivariate analysis demonstrated parametrial invasion and pelvic node
      metastasis were independent risk factors for DFS and OS rates. Further analyses
      showed that adjuvant therapy could significantly enhance DFS and OS rates in
      patients without the above independent risk factors. CONCLUSIONS: Patients with
      combination of pelvic node metastasis and parametrial invasion have the poorest
      prognosis, and adjuvant therapy significantly increases DFS and OS rates among
      patients without parametrial invasion and pelvic node metastasis.

PMID- 24937637
TI  - Anomalous enhancement in interfacial perpendicular magnetic anisotropy through
      uphill diffusion.
AB  - We observed interfacial chemical sharpening due to uphill diffusion in post
      annealed ultrathin multilayer stack of Co and Pt, which leads to enhanced
      interfacial perpendicular magnetic anisotropy (PMA). This is surprising as these
      elements are considered as perfectly miscible. This chemical sharpening was
      confirmed through quantitative energy dispersive x-ray (EDX) spectroscopy and
      intensity distribution of images taken on high angle annular dark field (HAADF)
      detector in Scanning Transmission Electron Microscopic (STEM) mode. This
      observation demonstrates an evidence of miscibility gap in ultrathin coherent
      Co/Pt multilayer stacks. 

PMID- 24937638
TI  - Stronger association of indoor temperature than outdoor temperature with blood
      pressure in colder months.
AB  - BACKGROUND: Higher cardiovascular mortality in winter may be partly explained by
      increased blood pressure (BP) because of cold exposure. However, this winter
      excess mortality is higher in countries with moderate winter than those with
      severe winter climate. OBJECTIVES: Although higher BP in low outdoor temperatures
      has been reported, the magnitude of association of indoor temperature with
      ambulatory BP remained unclear. We aimed to compare the associations of indoor
      and outdoor temperature with ambulatory BP. METHODS: From repeated measurements
      on two consecutive days during colder months (October-April) among 868 elderly
      individuals, we assessed the association of indoor and outdoor temperatures with
      ambulatory BP using multilevel analysis with random intercept for each
      individual. RESULTS: Correlation between indoor and outdoor temperature got weak
      along with decreasing outdoor temperature. Outdoor temperature was not
      significantly associated with ambulatory BP. In contrast, a 1 degrees C lower
      indoor temperature was significantly associated with 0.22 mmHg higher daytime
      SBP, 0.18% higher nocturnal BP fall, 0.34 mmHg higher sleep-trough morning BP
      surge independent of potential confounders including physical activity. The
      models with indoor temperature showed better fit of the model than those with
      outdoor temperature. Night-time SBP did not show significant association with
      indoor and outdoor temperature but with bed temperature. DISCUSSION: Our results
      suggest the importance to assess the association of indoor temperature with
      cardiovascular mortality to determine whether improving housing thermal
      environment reduces winter excess mortality. CONCLUSION: Indoor temperature
      showed stronger association than outdoor temperature with BP in colder months.

PMID- 24937636
TI  - Development of a multiplex methylation specific PCR suitable for (early)
      detection of non-small cell lung cancer.
AB  - Lung cancer is a worldwide health problem and a leading cause of cancer-related
      deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter
      methylation is an early event in the initiation and development of cancer. Thus,
      methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for
      early cancer detection. We have now developed a "Multiplex Methylation Specific
      PCR" (MMSP) assay for analysis of the methylation status of multiple potential
      TSGs by a single PCR reaction. This method will be useful for early diagnosis and
      treatment outcome studies of non-small cell lung cancer (NSCLC). Genome-wide CpG
      methylation and expression microarrays were performed on lung cancer tissues and
      matched distant non-cancerous tissues from three NSCLC patients from China.
      Thirty-eight potential TSGs were selected and analyzed by methylation PCR on
      bisulfite treated DNA. On the basis of sensitivity and specificity, six marker
      genes, HOXA9, TBX5, PITX2, CALCA, RASSF1A, and DLEC1, were selected to establish
      the MMSP assay. This assay was then used to analyze lung cancer tissues and
      matched distant non-cancerous tissues from 70 patients with NSCLC, as well as 24
      patients with benign pulmonary lesion as controls. The sensitivity of the assay
      was 99% (69/70). HOXA9 and TBX5 were the 2 most sensitive marker genes: 87%
      (61/70) and 84% (59/70), respectively. RASSF1A and DLEC1 showed the highest
      specificity at 99% (69/70). Using the criterion of identifying at least any two
      methylated marker genes, 61/70 cancer samples were positive, corresponding to a
      sensitivity of 87% and a specificity of 94%. Early stage I or II NSCLC could even
      be detected with a 100% specificity and 86% sensitivity. In conclusion, MMSP has
      the potential to be developed into a population-based screening tool and can be
      useful for early diagnosis of NSCLC. It might also be suitable for monitoring
      treatment outcome and recurrence. 

PMID- 24937639
TI  - Estimation of central aortic blood pressure: a systematic meta-analysis of
      available techniques.
AB  - BACKGROUND: Central aortic blood pressure (cBP) is often promoted to be a
      superior predictor of cardiovascular risk compared to brachial blood pressure,
      and brachial-central pulse pressure amplification is also suggested as
      prognostic. Several devices and techniques, each purporting to estimate cBP, have
      entered commercial use. The interchangeability of cBP measurements between
      devices and the influence of disease states on central to brachial pulse pressure
      amplification remain unclear. The useful measurement of cBP in clinical trials is
      dependent on clarification of these issues. METHOD: We performed a systematic
      meta-analysis of studies reporting cBP between 2000 and 2012. Studies were
      included if both central and brachial SBPs (cSBP and bSBP) were reported. Studies
      were categorized by technique and according to the prevalent disease state with
      the bSBP - cSBP difference calculated. Random-effects modeling (inverse variance
      weighted approach) was used to estimate the pooled mean difference associated
      with each technique. RESULTS: Of the 164 eligible studies, the SphygmoCor device
      was most commonly reported (110 studies), with direct carotid applanation second
      most utilized (31 studies). In 30 included invasive cohorts, the measured cSBP
      did not differ significantly from the oscillometric bSBP recorded [mean
      difference 4.19  mmHg, 95% confidence interval (CI) -4.13 to 12.51], whereas mean
      differences of 12.77  mmHg (95% CI 11.93, 13.60) and 8.83  mmHg (95% CI 7.86,
      9.79) were obtained with the SphygmoCor and carotid applanation estimates of
      cSBP, respectively (both P < 0.05). Conversely, the reported mean cSBP-to-bSBP
      differences measured across various disease states with SphygmoCor did not differ
      significantly. CONCLUSION: This meta-analysis suggests that noninvasive cBP
      estimation is device/technique-dependent. Consequently, caution is advisable in
      applying these devices and techniques across clinical studies.

PMID- 24937641
TI  - Waterfowl conservation in the US Prairie Pothole Region: confronting the
      complexities of climate change.
AB  - The Prairie Pothole Region (PPR) is the most important waterfowl production area
      in North America. However, waterfowl populations there are predicted to decline
      because of climate-related drying of wetlands. Consequently, changes in the
      geographic focus of PPR waterfowl conservation have been recommended, which could
      have long-lasting and costly impacts. We used a 40-year dataset of pond counts
      collected in the PPR to test hypotheses about climate-related drying. We assessed
      May (1974-2013) and July (1974-2003) pond numbers in 20 waterfowl survey strata
      to determine if trends in pond numbers were consistent with predictions of
      drying. We also assessed trends in precipitation and temperature for the 20
      strata and developed models describing May pond numbers from 1974 through 2010 as
      a function of precipitation, temperature, the previous year's pond numbers, and
      location. None of the 20 strata showed significant declines in May pond numbers,
      although seven strata showed increases over time. July pond numbers declined
      significantly in one stratum, and increased in seven strata. An index to
      hydroperiod showed significant increasing trends in three strata, and no strata
      had decreasing trends. Precipitation increased significantly in two strata and
      decreased in two from 1974 to 2010; no strata showed significant changes in
      temperature. The best linear model described pond numbers within all strata as a
      function of precipitation, temperature, the previous year's pond numbers, and the
      latitude and longitude of the stratum, and explained 62% of annual variation in
      pond numbers. We hypothesize that direct effects of climate change on prairie
      pothole wetlands and waterfowl may be overshadowed by indirect effects such as
      intensified land use and increased pressure to drain wetlands. We recommend that
      an adaptive, data-driven approach be used to resolve uncertainties regarding
      direct and indirect effects of climate change on prairie wetlands and waterfowl,
      and guide future conservation efforts. 

PMID- 24937642
TI  - Decarboxylative polymerization of 2,6-naphthalenedicarboxylic acid at surfaces.
AB  - Metal-catalyzed polymerization of 2,6-naphthalenedicarboxylic acid (NDCA) to form
      poly-2,6-naphthalenes at various surfaces is reported. Polymerizations occur via
      initial formal dehydrogenation of self-assembled diacids with subsequent
      decarboxylation to give polymeric bisnaphthyl-Cu species at elevated temperature
      as intermediate structures (<160  degrees C). Further temperature increase
      eventually leads to poly-naphthalenes via reductive elimination. It is
      demonstrated that the Cu(111) surface works most efficiently to conduct such
      polymerizations as compared to the Au(111), Ag(111), Cu(100), and Cu(110)
      surfaces. Poly-2,6-naphthalene with a chain length of over 50 nm is obtained by
      using this approach. The decarboxylative coupling of aromatic diacids is a very
      promising tool which further enlarges the portfolio of reactions allowing for on
      surface polymerizations and novel organometallic systems preparations. 

PMID- 24937644
TI  - Clearing the air on SUDEP: vote to ban smoking among people with epilepsy.

PMID- 24937643
TI  - Bosentan in pulmonary hypertension associated with fibrotic idiopathic
      interstitial pneumonia.
AB  - RATIONALE: Pulmonary hypertension (PH) associated with fibrotic idiopathic
      interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific
      interstitial pneumonia) confers important additional morbidity and mortality.
      OBJECTIVES: To evaluate the safety and clinical efficacy of the dual endothelin-1
      receptor antagonist bosentan in this patient group. METHODS: In a randomized,
      double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right
      heart catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo
      (n = 20). The primary study endpoint was a fall from baseline pulmonary vascular
      resistance index (PVRi) of 20% or more over 16 weeks. MEASUREMENTS AND MAIN
      RESULTS: Sixty patients (42 men; mean age, 66.6 +/- 9.2 yr), with a mean
      pulmonary artery pressure of 36.0 (+/- 8.9) mm Hg, PVRi 13.0 (+/- 6.7) Wood
      Units/m(2) and reduced cardiac index of 2.21 (+/- 0.5) L/min/m(2) were recruited
      to the study. Accounting for deaths and withdrawals, paired right heart catheter
      data were available for analysis in 39 patients (bosentan = 25, placebo = 14). No
      difference in the primary outcome was detected, with seven (28.0%) patients
      receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in
      PVRi of greater than or equal to 20% (P = 0.97) at 16 weeks. There was no change
      in functional capacity or symptoms between the two groups at 16 weeks, nor any
      difference in rates of serious adverse events or deaths (three deaths in each
      group). CONCLUSIONS: This study shows no difference in invasive pulmonary
      hemodynamics, functional capacity, or symptoms between the bosentan and placebo
      groups over 16 weeks. Our data do not support the use of the dual endothelin-1
      receptor antagonist, bosentan, in patients with PH and fibrotic IIP. Clinical
      trial registered with www.clinicaltrials.gov (NCT 00637065).

PMID- 24937645
TI  - Comparative mapping of the wild perennial Glycine latifolia and soybean (G. max)
      reveals extensive chromosome rearrangements in the genus Glycine.
AB  - Soybean (Glycine max L. Mer.), like many cultivated crops, has a relatively
      narrow genetic base and lacks diversity for some economically important traits.
      Glycine latifolia (Benth.) Newell & Hymowitz, one of the 26 perennial wild
      Glycine species related to soybean in the subgenus Glycine Willd., shows high
      levels of resistance to multiple soybean pathogens and pests including Alfalfa
      mosaic virus, Heterodera glycines Ichinohe and Sclerotinia sclerotiorum (Lib.) de
      Bary. However, limited information is available on the genomes of these perennial
      Glycine species. To generate molecular resources for gene mapping and
      identification, high-density linkage maps were constructed for G. latifolia using
      single nucleotide polymorphism (SNP) markers generated by genotyping by
      sequencing and evaluated in an F2 population and confirmed in an F5 population.
      In each population, greater than 2,300 SNP markers were selected for analysis and
      segregated to form 20 large linkage groups. Marker orders were similar in the F2
      and F5 populations. The relationships between G. latifolia linkage groups and G.
      max and common bean (Phaseolus vulgaris L.) chromosomes were examined by aligning
      SNP-containing sequences from G. latifolia to the genome sequences of G. max and
      P. vulgaris. Twelve of the 20 G. latifolia linkage groups were nearly collinear
      with G. max chromosomes. The remaining eight G. latifolia linkage groups appeared
      to be products of multiple interchromosomal translocations relative to G. max.
      Large syntenic blocks also were observed between G. latifolia and P. vulgaris.
      These experiments are the first to compare genome organizations among annual and
      perennial Glycine species and common bean. The development of molecular resources
      for species closely related to G. max provides information into the evolution of
      genomes within the genus Glycine and tools to identify genes within perennial
      wild relatives of cultivated soybean that could be beneficial to soybean
      production. 

PMID- 24937646
TI  - Impacts of the Callipyge mutation on ovine plasma metabolites and muscle fibre
      type.
AB  - The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the
      pelvic limbs and torso, as well as body leanness. The mechanism underpinning
      enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using
      muscle fibre typing immunohistochemistry, we confirmed muscle specific effects
      and demonstrated that affected muscles had greater prevalence and hypertrophy of
      type 2X fast twitch glycolytic fibres and decreased representation of types 1,
      2C, 2A and/or 2AX fibres. To investigate potential systemic effects of the
      mutation, proton NMR spectra of plasma taken from lambs at 8 and 12 weeks of age
      were measured. Multivariate statistical analysis of plasma metabolite profiles
      demonstrated effects of development and genotype but not gender. Plasma from
      Callipyge lambs at 12 weeks of age, but not 8 weeks, was characterized by a
      metabolic profile consistent with contributions from the affected hypertrophic
      fast twitch glycolytic muscle fibres. Microarray analysis of the perirenal
      adipose tissue depot did not reveal a transcriptional effect of the mutation in
      this tissue. We conclude that there is an indirect systemic effect of the
      Callipyge mutation in skeletal muscle in the form of changes of blood
      metabolites, which may contribute to secondary phenotypes such as body leanness. 

PMID- 24937647
TI  - Predicting the risk of avian influenza A H7N9 infection in live-poultry markets
      across Asia.
AB  - Two epidemic waves of an avian influenza A (H7N9) virus have so far affected
      China. Most human cases have been attributable to poultry exposure at live
      poultry markets, where most positive isolates were sampled. The potential
      geographic extent of potential re-emerging epidemics is unknown, as are the
      factors associated with it. Using newly assembled data sets of the locations of
      8,943 live-poultry markets in China and maps of environmental correlates, we
      develop a statistical model that accurately predicts the risk of H7N9 market
      infection across Asia. Local density of live-poultry markets is the most
      important predictor of H7N9 infection risk in markets, underscoring their key
      role in the spatial epidemiology of H7N9, alongside other poultry, land cover and
      anthropogenic predictor variables. Identification of areas in Asia with high
      suitability for H7N9 infection enhances our capacity to target biosurveillance
      and control, helping to restrict the spread of this important disease. 

PMID- 24937650
TI  - Physical literacy and Comprehensive School Physical Activity Programs.
AB  - OBJECTIVE: The purpose of this paper is to make a case for Comprehensive School
      Physical Activity Program (CSPAP) to be the organizational framework for
      providing physical activity opportunities for children that is most likely to
      result in physical literacy. METHOD: Beginning in 2010, the authors used multiple
      search engines to ascertain the existent literature surrounding physical literacy
      and physical activity interventions to identify common approaches to providing
      physically activity in and around school. Grounded in the Health Belief Model and
      the idea that physical literacy is a desired outcome of physical education,
      publications focused on each of the components of the CSPAP were synthesized to
      describe evidence-based practice. RESULTS: There is adequate evidence to suggest
      that quality physical education, before/after school, during school, staff
      involvement, and family and community engagement can serve as logical points of
      intervention to provide increased opportunities for physical activity
      participation leading to physical literacy among children. CONCLUSIONS: Since
      only 6% of all children participate in daily physical education classes and only
      six states offer K-12 physical education, the implementation of CSPAP may be the
      most logical avenue for providing greater opportunities for physical activity
      engagement that fosters physical literacy as a health-oriented educational goal.

PMID- 24937649
TI  - Why behavior change is difficult to sustain.
AB  - Unhealthy behavior is responsible for much human disease, and a common goal of
      contemporary preventive medicine is therefore to encourage behavior change.
      However, while behavior change often seems easy in the short run, it can be
      difficult to sustain. This article provides a selective review of research from
      the basic learning and behavior laboratory that provides some insight into why.
      The research suggests that methods used to create behavior change (including
      extinction, counterconditioning, punishment, reinforcement of alternative
      behavior, and abstinence reinforcement) tend to inhibit, rather than erase, the
      original behavior. Importantly, the inhibition, and thus behavior change more
      generally, is often specific to the "context" in which it is learned. In support
      of this view, the article discusses a number of lapse and relapse phenomena that
      occur after behavior has been changed (renewal, spontaneous recovery,
      reinstatement, rapid reacquisition, and resurgence). The findings suggest that
      changing a behavior can be an inherently unstable and unsteady process; frequent
      lapses should be expected. In the long run, behavior-change therapies might
      benefit from paying attention to the context in which behavior change occurs. 

PMID- 24937648
TI  - Longitudinal predictors of colorectal cancer screening among participants in a
      randomized controlled trial.
AB  - OBJECTIVE: Few studies use longitudinal data to identify predictors of colorectal
      cancer screening (CRCS). We examined predictors of (1) initial CRCS during the
      first year of a randomized trial, and (2) repeat CRCS during the second year of
      the trial among those that completed FOBT in Year 1. METHODS: The sample
      comprised 1247 participants of the Systems of Support to Increase Colorectal
      Cancer Screening (SOS) Trial (Group Health Cooperative, August 2008 to November
      2011). Potential predictors of CRCS were identified with logistic regression and
      included sociodemographics, health history, and validated scales of psychosocial
      constructs. RESULTS: Prior CRCS (OR 2.64, 95% CI 1.99-3.52) and intervention
      group (Automated: OR 2.06 95% CI 1.43-2.95; Assisted: OR 4.03, 95% CI 2.69-6.03;
      Navigated: OR 5.64, 95% CI 3.74-8.49) were predictors of CRCS completion at Year
      1. For repeat CRCS at Year 2, prior CRCS at baseline (OR 1.97, 95% CI 1.25-3.11),
      intervention group (Automated: OR 9.27, 95% CI 4.56-18.82; Assisted: OR 11.17,
      95% CI 5.44-22.94; Navigated: OR 13.10, 95% CI 6.33-27.08), and self-efficacy (OR
      1.32, 95% CI 1.00-1.73) were significant predictors. CONCLUSION: Self-efficacy
      and prior CRCS are important predictors of future screening behavior. CRCS
      completion increased when access barriers were removed through interventions.

PMID- 24937651
TI  - Can the life-history strategy explain the success of the exotic trees Ailanthus
      altissima and Robinia pseudoacacia in Iberian floodplain forests?
AB  - Ailanthus altissima and Robina pseudoacacia are two successful invasive species
      of floodplains in central Spain. We aim to explain their success as invaders in
      this habitat by exploring their phenological pattern, vegetative and sexual
      reproductive growth, and allometric relations, comparing them with those of the
      dominant native tree Populus alba. During a full annual cycle we follow the
      timing of vegetative growth, flowering, fruit set, leaf abscission and fruit
      dispersal. Growth was assessed by harvesting two-year old branches at the peaks
      of vegetative, flower and fruit production and expressing the mass of current
      year leaves, stems, inflorescences and infrutescences per unit of previous-year
      stem mass. Secondary growth was assessed as the increment of trunk basal area per
      previous-year basal area. A. altissima and R. pseudoacacia showed reproductive
      traits (late flowering phenology, insect pollination, late and long fruit set
      period, larger seeds) different from P. alba and other native trees, which may
      help them to occupy an empty reproductive niche and benefit from a reduced
      competition for the resources required by reproductive growth. The larger seeds
      of the invaders may make them less dependent on gaps for seedling establishment.
      If so, these invaders may benefit from the reduced gap formation rate of flood
      regulated rivers of the study region. The two invasive species showed higher
      gross production than the native, due to the higher size of pre-existing stems
      rather than to a faster relative growth rate. The latter was only higher in A.
      altissima for stems, and in R. pseudoacacia for reproductive organs. A. altissima
      and R. pseudoacacia showed the lowest and highest reproductive/vegetative mass
      ratio, respectively. Therefore, A. altissima may outcompete native P. alba trees
      thanks to a high potential to overtop coexisting plants whereas R. pseudoacacia
      may do so by means of a higher investment in sexual reproduction. 

PMID- 24937652
TI  - The effect of health education video on ocular massage after trabeculectomy.
AB  - The aim of this study was to investigate the effect of different ocular massage
      health education methods on ocular massage in glaucoma patients after
      trabeculectomy. Eighty-six patients with glaucoma after trabeculectomy (86 eyes)
      were randomly divided into two health education groups. One group was a watch
      video group (43 patients, 43 eyes), while the other was an orally taught health
      education group (43 patients, 43 eyes). Patients were followed up for 1 week, 1
      month, and 3, 6, and 12 months after discharge. Records of the patient responses
      after health education, compliance of patients with follow-up, and intraocular
      pressure were determined. Measurements included intraocular pressure and
      differences between the watch video and orally taught health education groups.
      The differences between the watch video group and orally taught health education
      group were not statistically significant at 1 week and 1 month, while the
      differences were statistically significant at 3, 6, and 12 months. The results
      indicated that health education videos can enable glaucoma patients to have a
      better mastery of ocular massage after trabeculectomy. According to the needs of
      patients, health education video use produced good results and should be
      promoted. 

PMID- 24937654
TI  - Neuropeptide proenkephalin A is associated with in-hospital mortality in patients
      with acute intracerebral hemorrhage.
AB  - High plasma proenkephalin A (PENK-A) levels are associated with poor clinical
      outcome after ischemic stroke. However, not much is known regarding the change of
      its level in acute intracerebral hemorrhage. Thus, we sought to determine PENK-A
      in plasma of patients with acute spontaneous basal ganglia hemorrhage and
      evaluate its relation with disease severity and in-hospital mortality. One
      hundred and two patients and 100 healthy controls were recruited. Plasma samples
      were obtained on admission for patients and at study entry for controls. Its
      concentration was measured by chemoluminescence sandwich immunoassay. Plasma PENK
      A levels were substantially higher in patients than in healthy controls (235.5+/
      85.4 pmol/L vs. 90.1+/-31.3 pmol/L; P<0.0001). A forward stepwise logistic
      regression selected plasma PENK-A as an independent predictor for in-hospital
      mortality of patients (odds ratio 1.080, 95% confidence interval 1.018-1.147,
      P<0.001). A multivariate linear regression demonstrated that plasma PENK-A level
      was positively associated with National Institutes of Health Stroke Scale (NIHSS)
      score (t=6.189, P<0.001) and hematoma volume (t=5.388, P<0.001). A receiver
      operating characteristic curve identified a plasma PENK-A level>267.1 pmol/L
      predicted in-hospital mortality of patients with 80.0% sensitivity and 74.7%
      specificity (area under curve, 0.836; 95% confidence interval, 0.750-0.902). Its
      predictive value was similar to NIHSS score's and hematoma volume's (both
      P>0.05). However, it did not statistically significantly improve the predictive
      values of NIHSS score and hematoma volume (both P>0.05). Thus, increased plasma
      PENK-A levels are associated with disease severity and in-hospital mortality
      after acute intracerebral hemorrhage.

PMID- 24937653
TI  - GLP-1(32-36)amide, a novel pentapeptide cleavage product of GLP-1, modulates
      whole body glucose metabolism in dogs.
AB  - We have previously demonstrated in human subjects who under euglycemic clamp
      conditions GLP-1(9-36)amide infusions inhibit endogenous glucose production
      without substantial insulinotropic effects. An earlier report indicates that GLP
      1(9-36)amide is cleaved to a nonapeptide, GLP-1(28-36)amide and a pentapeptide
      GLP-1(32-36)amide (LVKGR amide). Here we study the effects of the pentapeptide on
      whole body glucose disposal during hyperglycemic clamp studies. Five dogs
      underwent indwelling catheterizations. Following recovery, the dogs underwent a
      180 min hyperglycemic clamp (basal glucose +98 mg/dl) in a cross-over design.
      Saline or pentapeptide (30 pmol kg(-1) min(-1)) was infused during the last 120
      min after commencement of the hyperglycemic clamp in a primed continuous manner.
      During the last 30 min of the pentapeptide infusion, glucose utilization (M)
      significantly increased to 21.4+/-2.9 mg kg(-1) min(-1)compared to M of 14.3+/
      1.1 mg kg(-1)min(-1) during the saline infusion (P=0.026, paired t-test; P=0.062,
      Mann-Whitney U test). During this interval, no significant differences in insulin
      (26.6+/-3.2 vs. 23.7+/-2.5 MUU/ml, P=NS) or glucagon secretion (34.0+/-2.1 vs.
      31.7+/-1.8 pg/ml, P=NS) were observed. These findings demonstrate that under
      hyperglycemic clamp studies the pentapeptide modulates glucose metabolism by a
      stimulation of whole-body glucose disposal. Further, the findings suggest that
      the metabolic benefits previously observed during GLP-1(9-36)amide infusions in
      humans might be due, at least in part, to the metabolic effects of the
      pentapeptide that is cleaved from the pro-peptide, GLP-1(9-36)amide in the
      circulation.

PMID- 24937655
TI  - Prognostic value of neuropeptide proenkephalin A in patients with severe
      traumatic brain injury.
AB  - High plasma proenkephalin A levels have been associated with poor clinical
      outcome of aneurysmal subarachnoid hemorrhage. This prospective observatory study
      was designed to investigate the relationship between plasma proenkephalin A
      levels and 1-week mortality, 6-month mortality and 6-month unfavorable outcome
      (defined as Glasgow Outcome Scale score of 1-3) in patients with severe traumatic
      brain injury. This study recruited 128 patients and 128 sex- and age-matched
      healthy controls. Plasma proenkephalin A levels, as measured by chemoluminescence
      sandwich immunoassay, were statistically significantly higher in patients than in
      healthy controls (239.1+/-93.0 pmol/L vs.81.3+/-22.1 pmol/L; P<0.001) and were
      correlated with Glasgow Coma Scale scores (r=-0.540, P<0.001). It was identified
      as an independent prognostic predictor of 1-week mortality [odds ratio (OR),
      1.214; 95% confidence interval (CI), 1.103-1.425; P<0.001], 6-month mortality
      (OR, 1.162; 95% CI, 1.101-1.372; P<0.001) and 6-month unfavorable outcome (OR,
      1.116; 95% CI, 1.097-1.281; P<0.001). Moreover, it had high predictive value for
      1-week mortality [area under curve (AUC), 0.852; 95% CI, 0.778-0.908], 6-month
      mortality (AUC, 0.841; 95% CI, 0.766-0.899) and 6-month unfavorable outcome (AUC,
      0.830; 95% CI, 0.754-0.891). Furthermore, its predictive value was similar to
      Glasgow Coma Scale score's (all P>0.05). Yet, a combined logistic-regression
      model did not show that it statistically significantly improved the predictive
      value of Glasgow Coma Scale score (all P>0.05). Thus, it was proposed that
      enhanced plasma proenkephalin A could be a useful, complementary tool to predict
      short- or long-term clinical outcome after severe traumatic brain injury.

PMID- 24937657
TI  - Risks of toxic ash from artisanal mining of discarded cellphones.
AB  - The potential environmental and human health impacts of artisanal mining of
      electronic waste through open incineration were investigated. A market
      representative set of cellphones was dismantled into four component categories
      batteries, circuit boards, plastics and screens. The components were shredded,
      sieved and incinerated at 743-818  degrees C. The concentrations of 17 metals
      were determined using U.S. EPA methods 6010C (inductively coupled plasma-atomic
      emission spectrometry; 6020A (inductively coupled plasma-mass spectrometry, or
      7471B and 7470A (cold-vapor atomic absorption). EPA Method 8270 (gas
      chromatography/mass spectrometry) was used to identify polyaromatic hydrocarbon
      compounds and polybrominated diphenyl ethers. EPA Method 8082A was used to
      measure polychlorinated biphenyls and EPA Method 8290 was used for dioxin/furans
      in the residue ash. The life cycle assessment model USEtox((r)) was used to
      estimate impacts of the ash residue chemicals on human health and the ecosystem.
      Among metals, copper in printed circuit boards had the highest ecotoxicity impact
      (1610-1930PAFm(3)/kg); Beryllium in plastics had the highest impact on producing
      non-cancer diseases (0.14-0.44 cases/kg of ash); and Nickel had the largest
      impact on producing cancers (0.093-0.35 cases/kg of ash). Among organic
      chemicals, dioxins from incinerated batteries produced the largest
      ecotoxicological impact (1.07E-04 to 3.64E-04PAFm(3)/kg). Furans in incinerated
      batteries can generate the largest number of cancers and non-cancer diseases,
      representing 8.12E-09 to 2.28E-08 and 8.96E-10 and 2.52E-09 cases/kg of ash,
      respectively. The results reveal hazards of burning discarded cellphones to
      recover precious metals, and pinpoints opportunities for manufacturers to reduce
      toxic materials used in specific electronic components marketed globally.

PMID- 24937656
TI  - miR-451 deficiency is associated with altered endometrial fibrinogen alpha chain
      expression and reduced endometriotic implant establishment in an experimental
      mouse model.
AB  - Endometriosis is defined as the growth of endometrial glandular and stromal
      components in ectopic locations and affects as many as 10% of all women of
      reproductive age. Despite its high prevalence, the pathogenesis of endometriosis
      remains poorly understood. MicroRNAs, small non-coding RNAs that post
      transcriptionally regulate gene expression, are mis-expressed in endometriosis
      but a functional role in the disease pathogenesis remains uncertain. To examine
      the role of microRNA-451 (miR-451) in the initial development of endometriosis,
      we utilized a novel mouse model in which eutopic endometrial fragments used to
      induce endometriosis were deficient for miR-451. After induction of the disease,
      we evaluated the impact of this deficiency on implant development and survival.
      Loss of miR-451 expression resulted in a lower number of ectopic lesions
      established in vivo. Analysis of differential protein profiles between miR-451
      deficient and wild-type endometrial fragments revealed that fibrinogen alpha
      polypeptide isoform 2 precursor was approximately 2-fold higher in the miR-451
      null donor endometrial tissue and this elevated expression of the protein was
      associated with altered expression of the parent fibrinogen alpha chain mRNA and
      protein. As this polypeptide contains RGD amino acid "cell adhesion" motifs which
      could impact early establishment of lesion development, we examined and confirmed
      using a cyclic RGD peptide antagonist, that endometrial cell adhesion and
      endometriosis establishment could be respectively inhibited both in vitro and in
      vivo. Collectively, these results suggest that the reduced miR-451 eutopic
      endometrial expression does not enhance initial establishment of these fragments
      when displaced into the peritoneal cavity, that loss of eutopic endometrial miR
      451 expression is associated with altered expression of fibrinogen alpha chain
      mRNA and protein, and that RGD cyclic peptide antagonists inhibit establishment
      of endometriosis development in an experimental mouse model suggesting that this
      approach may prove useful in the prevention of endometriosis establishment and
      survival. 

PMID- 24937658
TI  - Electro-enhanced removal of copper ions from aqueous solutions by capacitive
      deionization.
AB  - This study was performed to determine the feasibility of electrosorptive removal
      of copper ions from aqueous solutions using a capacitive deionization process.
      The electrosorptive potential of copper ions was determined using cyclic
      voltammetry measurements, and copper electrodeposition could be suppressed at a
      voltage less than 0.8 V. Importantly, the experimental results demonstrated a
      significant enhancement of electrosorption capability of copper ions using the
      activated carbon electrodes under electro-assistance, associated with electrical
      double-layer charging. At 0.8 V, the equilibrium electrosorption capacity was
      enhanced to 24.57 mg/g based on the Langmuir model, and the electrosorption
      constant rate was increased to 0.038 min(-1) simulated by a first-order kinetics
      model. Moreover, the activated carbon electrode showed great regeneration
      performance for the removal of low level copper ions. Additional experiments
      regarding electrosorption selectivity were performed in the presence of sodium
      chloride, natural organic matter, or dissolved silica. Copper ions that were
      preferentially electroadsorbed on the electrode surface can be effectively
      removed in a competitive environment. Therefore, the electrosorption process
      using activated carbon electrodes can be recommended to treat copper solutions at
      low concentrations for wastewater treatment and water purification.

PMID- 24937659
TI  - Degradation of estrone in water and wastewater by various advanced oxidation
      processes.
AB  - A comprehensive study was conducted to determine the relative efficacy of various
      advanced oxidation processes such as O3, H2O2, UV, and combinations of UV/O3,
      UV/H2O2 for the removal of estrone (E1) from pure water and secondary effluent.
      In addition to the parent compound (E1) removal, performance of the advanced
      oxidation processes was characterized using removal of total organic carbon
      (TOC), and estrogenicity of the effluent. Although E1 removal was high for all
      the AOPs, intermediates formed were more difficult to degrade leading to slow TOC
      removal. Energy calculations and cost analysis indicated that, although UV
      processes have low electricity cost, ozonation is the least cost option ($
      0.34/1000 gallons) when both capital and operating costs were taken into account.
      Ozonation also is superior to the other tested AOPs due to higher removal of TOC
      and estrogenicity. The rate of E1 removal decreased linearly with the background
      TOC in water, however, E1 degradation in the secondary effluent from a local
      wastewater treatment plant was not affected significantly due to the low COD
      values in the effluent. 

PMID- 24937661
TI  - An integrated approach for enhanced protein conjugation and capture with viral
      nanotemplates and hydrogel microparticle platforms via rapid bioorthogonal
      reactions.
AB  - We demonstrate significantly enhanced protein conjugation and target protein
      capture capacity by exploiting tobacco mosaic virus (TMV) templates assembled
      with hydrogel microparticles. Protein conjugation results with a red fluorescent
      protein R-Phycoerythrin (R-PE) show significantly enhanced protein conjugation
      capacity of TMV-assembled particles (TMV-particles) compared to planar substrates
      or hydrogel microparticles. In-depth examination of protein conjugation kinetics
      via tetrazine (Tz)-trans-cyclooctene (TCO) cycloaddition and strain-promoted
      alkyne-azide cycloaddition (SPAAC) reaction demonstrates that TMV-particles
      provide a less hindered environment for protein conjugation. Target protein
      capture results using an anti-R-PE antibody (R-Ab)-R-PE pair also show
      substantially improved capture capacity of R-Ab conjugated TMV-particles over R
      Ab conjugated hydrogel microparticles. We further demonstrate readily controlled
      protein and antibody conjugation capacity by simply varying TMV concentrations,
      which show negligible negative impact of densely assembled TMVs on protein
      conjugation and capture capacity. Combined, these results illustrate a facile
      postfabrication protein conjugation approach with TMV templates assembled onto
      hydrogel microparticles for improved and controlled protein conjugation and
      sensing platforms. We anticipate that our approach can be readily applied to
      various protein sensing applications. 

PMID- 24937660
TI  - Lifespan psychomotor behaviour profiles of multigenerational prenatal stress and
      artificial food dye effects in rats.
AB  - The consumption of artificial food dye (AFD) during childhood and adolescence has
      been linked to behavioural changes, such as hyperactivity. It is possible that
      the vulnerability to AFDs is modified by prenatal stress. Common consequences of
      prenatal stress include hyperactivity, thus potentially leading to synergistic
      actions with AFDs. Here, we investigated the compounding effect of
      multigenerational prenatal stress (MPS) and AFD consumption on the development of
      hyperactivity and anxiety-related behaviours across the lifespan in male rats.
      MPS treatment involved a family history of four consecutive generations of
      prenatal stress (F4 generation). AFD treatment included a 4%-concentration of
      FD&C Red 40, FD&C Yellow 5, FD&C Yellow 6, and FD&C Blue 1 in the drinking water
      from postnatal days 22 to 50 to resemble juvenile and adolescent dietary
      exposure. Using several exploration tasks, animals were tested in motor activity
      and anxiety-like behaviours from adolescence to 13 months of age. MPS resulted in
      hyperactivity both early (50 days) and later in life (13 months), with normalized
      activity patterns at reproductive age. AFD consumption resulted in hyperactivity
      during consumption, which subsided following termination of treatment. Notably,
      both MPS and AFD promoted risk-taking behaviour in young adults (3 months). There
      were few synergistic effects between MPS and AFD in this study. The findings
      suggest that AFDs exert the most noticeable effects at the time of exposure. MPS,
      however, results in a characteristic lifespan profile of behavioural changes,
      indicating that development and aging represent particularly vulnerable periods
      in life during which a family history of prenatal stress may precipitate. 

PMID- 24937662
TI  - ESR study of molecular orientation and dynamics of nitronyl nitroxide radicals in
      CLPOT 1D nanochannels.
AB  - New inclusion compounds (ICs) were prepared using the organic 1D nanochannels of
      2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) as a nanosized template and
      nitronyl nitroxide (NN) radicals such as phenylnitronylnitroxide (PhNN) and p
      nitrophenylnitronylnitroxide (p-NPNN). ESR measurements below 255 K for the CLPOT
      ICs diluted with spacer molecules gave rigid limit spectra similar to that for
      PhNN molecules in a glassy ethanol matrix at low temperature, which suggests
      isolation of the radical molecules. ESR measurements for them in the range of 290
      400 K gave a modulated quintet ESR signal, which suggested uniaxial rotational
      diffusion of NN radicals in the nanochannels approximately around the principal y
      axis of the g-tensors. In the ESR measurements to 430 K for the [(CLPOT)2-(p
      NPNN)0.07] IC without spacers, the broader line width than the case in dilution
      was observed by inter-radical dipolar interaction. In every case, the rotational
      diffusion activation energies of NN radicals in the CLPOT nanochannels were
      several times larger than those of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO)
      radical derivatives (4-X-TEMPO) in CLPOT nanochannels. This is expected due to
      the larger molecular size of NN radicals than 4-X-TEMPO or stronger interaction
      between NN radicals and the surrounding host or guest molecules. 

PMID- 24937663
TI  - Challenges in modelling the reaction chemistry of interstellar dust.
AB  - Studies aiming to understand the physicochemical properties of interstellar dust
      and the chemical reactions that occur on and in it have traditionally been the
      preserve of astronomical observation and experimental attempts to mimic
      astronomically relevant conditions in the laboratory. Increasingly, computational
      modelling in its various guises is establishing a complementary third pillar of
      support to this endeavour by providing detailed insights into the complexities of
      interstellar dust chemistry. Inherently, the basis of computational modelling is
      to be found in the details (e.g. atomic structure/composition, reaction barriers)
      that are difficult to probe accurately from observation and experiment. This
      bottom-up atom-based theoretical approach, often itself based on deeper quantum
      mechanical principles, although extremely powerful, also has limitations when
      systems become too large or complex. In this Perspective, after first providing a
      general background to the current state of observational-based knowledge, we
      introduce a number of computational modelling methods with reference to recent
      state-of-the-art studies, in order to highlight the capabilities of such
      approaches in this field. Specifically, we first outline the use of computational
      chemistry methods for dust nucleation, structure, and individual reactions on
      bare and icy dust surfaces. Later, we review kinetic modelling of networks of
      reactions relevant to dust chemistry and how to take into account quantum
      tunnelling effects in the low temperature reactions in the interstellar medium.
      Finally, we point to the future challenges that need to be overcome for
      computational modelling to provide even more detailed and encompassing
      perspectives on the nature and reaction chemistry of interstellar dust. 

PMID- 24937664
TI  - A putative OTU domain-containing protein 1 deubiquitinating enzyme is
      differentially expressed in thyroid cancer and identifies less-aggressive
      tumours.
AB  - BACKGROUND: This study aimed to identify novel biomarkers for thyroid carcinoma
      diagnosis and prognosis. METHODS: We have constructed a human single-chain
      variable fragment (scFv) antibody library that was selected against tumour
      thyroid cells using the BRASIL method (biopanning and rapid analysis of selective
      interactive ligands) and phage display technology. RESULTS: One highly reactive
      clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was
      confirmed by ELISA, which was further tested against a tissue microarray that
      comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid
      carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18
      normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The
      scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and
      reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have
      further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating
      enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel
      electrophoresis and mass spectrometry. CONCLUSIONS: The strategy of screening and
      identifying a cell-surface-binding antibody against thyroid tissues was highly
      effective and resulted in a useful biomarker that recognises malignancy among
      thyroid nodules and may help identify lower-risk cases that can benefit from less
      aggressive management.

PMID- 24937666
TI  - The role of a Mediterranean diet on the risk of oral and pharyngeal cancer.
AB  - BACKGROUND: The Mediterranean diet has a beneficial role on various neoplasms,
      but data are scanty on oral cavity and pharyngeal (OCP) cancer. METHODS: We
      analysed data from a case-control study carried out between 1997 and 2009 in
      Italy and Switzerland, including 768 incident, histologically confirmed OCP
      cancer cases and 2078 hospital controls. Adherence to the Mediterranean diet was
      measured using the Mediterranean Diet Score (MDS) based on the major
      characteristics of the Mediterranean diet, and two other scores, the
      Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean
      Adequacy Index (MAI). RESULTS: We estimated the odds ratios (ORs), and the
      corresponding 95% confidence intervals (CI), for increasing levels of the scores
      (i.e., increasing adherence) using multiple logistic regression models. We found
      a reduced risk of OCP cancer for increasing levels of the MDS, the ORs for
      subjects with six or more MDS components compared with two or less being 0.20
      (95% CI 0.14-0.28, P-value for trend <0.0001). The ORs for the highest vs the
      lowest quintile were 0.20 (95% CI 0.14-0.28) for the MDP score (score 66.2 or
      more vs less than 57.9), and 0.48 (95% CI 0.33-0.69) for the MAI score (score
      value 2.1 or more vs value less 0.92), with significant trends of decreasing risk
      for both scores. The favourable effect of the Mediterranean diet was apparently
      stronger in younger subjects, in those with a higher level of education, and in
      ex-smokers, although it was observed in other strata as well. CONCLUSIONS: Our
      study provides strong evidence of a beneficial role of the Mediterranean diet on
      OCP cancer.

PMID- 24937665
TI  - Dietary intake of acrylamide and endometrial cancer risk in the European
      Prospective Investigation into Cancer and Nutrition cohort.
AB  - BACKGROUND: Three prospective studies have evaluated the association between
      dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent
      results. The objective of this study was to evaluate the association between
      acrylamide intake and EC risk: for overall EC, for type-I EC, and in never
      smokers and never users of oral contraceptives (OCs). Smoking is a source of
      acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox
      regression was used to estimate hazard ratios (HRs) for the association between
      acrylamide intake and EC risk in the European Prospective Investigation into
      Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU
      acrylamide monitoring database, which was matched with EPIC questionnaire-based
      food consumption data. Acrylamide intake was energy adjusted using the residual
      method. RESULTS: No associations were observed between acrylamide intake and
      overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative
      risks for type-I EC with increasing acrylamide intake among women who both never
      smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood
      ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide
      was not associated with overall or type-I EC risk; however, positive associations
      with type I were observed in women who were both non-users of OCs and never
      smokers.

PMID- 24937667
TI  - Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney:
      a combined SIOP and AIEOP study.
AB  - BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric
      renal tumour. Relapses occur in about 15% of the patients. Since detailed
      clinical information on relapsed CCSK is scarce, the current study aims to
      describe outcome of patients with relapsed CCSK treated according to recent
      European protocols. PATIENTS AND METHODS: We analysed prospectively collected
      data of all CCSK patients who developed a relapse after complete remission at the
      end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and
      2012. RESULTS: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP
      and AIEOP protocols developed a relapse. Median time from initial diagnosis to
      relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty
      seven relapses (95%) were metastatic; the most common sites of relapse were the
      brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of
      chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high
      dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14
      patients. Twenty-two out of thirty-seven patients (59%) achieved a second
      complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year
      event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year
      overall survival (OS) was 26% (95% CI: 10%-42%). CONCLUSIONS: In this largest
      series of relapsed CCSK patients ever described, overall outcome is poor. Most
      relapses are metastatic and brain relapses are more common than previously
      recognised. Intensive treatment aiming for local control, followed by high dose
      chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel
      development of targeted therapy is urgently required.

PMID- 24937668
TI  - Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid
      correlates with lymphatic invasion and lymph node metastasis.
AB  - BACKGROUND: Association studies have implicated the glycosaminoglycan hyaluronan
      (hyaluronic acid, HA) and its degrading enzymes the hyaluronidases in tumour
      progression and metastasis. Oligosaccharides of degraded HA have been ascribed a
      number of biological functions that are not exerted by high-molecular-weight HA
      (HMW-HA). However, whether these small HA oligosaccharides (sHA) have a role in
      tumour progression currently remains uncertain due to an inability to analyse
      their concentration in tumours. METHODS: We report a novel method to determine
      the concentration of sHA ranging from 6 to 25 disaccharides in tumour
      interstitial fluid (TIF). Levels of sHA were measured in TIF from experimental
      rat tumours and human colorectal tumours. RESULTS: While the majority of HA in
      TIF is HMW-HA, concentrations of sHA up to 6 MUg ml(-1) were detected in a subset
      of tumours, but not in interstitial fluid from healthy tissues. In a cohort of 72
      colorectal cancer patients we found that increased sHA concentrations in TIF are
      associated with lymphatic vessel invasion by tumour cells and the formation of
      lymph node metastasis. CONCLUSIONS: These data document for the first time the
      pathophysiological concentration of sHA in tumours, and provide evidence of a
      role for sHA in tumour progression.

PMID- 24937670
TI  - DNA methylation status is more reliable than gene expression at detecting cancer
      in prostate biopsy.
AB  - BACKGROUND: We analysed critically the potential usefulness of RNA- and DNA-based
      biomarkers in supporting conventional histological diagnostic tests for prostate
      carcinoma (PCa) detection. METHODS: Microarray profiling of gene expression and
      DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32
      cancerous and non-cancerous prostate samples extracted by radical prostatectomy.
      The predictive value of the selected biomarkers was validated by qPCR-based
      methods using tissue samples extracted from the 58 prostates and, separately,
      using 227 prostate core biopsies. RESULTS: HOXC6, AMACR and PCA3 expression
      showed the best discrimination between PCa and BPH. All three genes were
      previously reported as the most promising mRNA-based markers for distinguishing
      cancerous lesions from benign prostate lesions; however, none were sufficiently
      sensitive and specific to meet the criteria for a PCa diagnostic biomarker. By
      contrast, DNA methylation levels of the APC, TACC2, RARB, DGKZ and HES5 promoter
      regions achieved high discriminating sensitivity and specificity, with area under
      the curve (AUCs) reaching 0.95-1.0. Only a small overlap was detected between the
      DNA methylation levels of PCa-positive and PCa-negative needle biopsies, with
      AUCs ranging between 0.854 and 0.899. CONCLUSIONS: DNA methylation-based
      biomarkers reflect the prostate malignancy and might be useful in supporting
      clinical decisions for suspected PCa following an initial negative prostate
      biopsy.

PMID- 24937669
TI  - Randomised controlled trial of doxorubicin-eluting beads vs conventional
      chemoembolisation for hepatocellular carcinoma.
AB  - BACKGROUND: Transcatheter arterial chemoembolisation (TACE) is the treatment of
      choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded
      drug-eluting beads (DEB)-TACE is expected to improve the performance of
      conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with
      cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2
      year survival. METHODS: Patients were randomised one-to-one to undergo cTACE or
      DEB-TACE and followed-up for at least 2 years or until death. Transcatheter
      arterial chemoembolisation was repeated 'on-demand'. RESULTS: We enrolled 177
      patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was
      2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323).
      No differences were found in local and overall tumour response. The median TTP
      was 9 months in both arms. The AE incidence and severity did not differ between
      the arms, except for post-procedural pain, more frequent and severe after cTACE
      (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE
      and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group
      (ECOG), serum albumin, and tumour number independently predicted survival
      (P<0.05). CONCLUSIONS: The DEB-TACE and the cTACE are equally effective and safe,
      with the only advantage of DEB-TACE being less post-procedural abdominal pain.

PMID- 24937671
TI  - IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell
      invasion via STAT3 and ERK signaling.
AB  - BACKGROUND: Interleukin-22 (IL-22) has been recently highlighted owing to its
      biological significance in the modulation of tissue responses during
      inflammation. However, the role of IL-22 in carcinogenesis has remained unclear.
      Here, we investigated the pathophysiological significance of IL-22 expression in
      gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric
      cancer cell invasion. METHODS: Human gastric cancer specimens were analysed by
      immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The
      effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric
      cancer cells were examined using a small-interfering RNA system and specific
      inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs)
      from human gastric cancer tissues and assessed by invasion assay. RESULTS:
      Interleukin-22 and its receptor were expressed in alpha-smooth muscle actin
      positive stromal cells and tumour cells at the invasive front of gastric cancer
      tissues, respectively. The expression of IL-22 and IL-22R1 was significantly
      related to lymphatic invasion. Interleukin-22 treatment promoted the invasive
      ability of gastric cancer cells through STAT3 and ERK activation. The invasive
      ability of gastric cancer cells was significantly enhanced by co-culture with IL
      22-expressing CAFs. CONCLUSIONS: Interleukin-22 produced by CAFs promotes gastric
      cancer cell invasion via STAT3 and ERK signalling.

PMID- 24937672
TI  - Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment
      response.
AB  - BACKGROUND: Resistance to chemotherapeutic agents is a major obstacle to cancer
      treatment. A group of ABC efflux pumps, the Multidrug Resistance Proteins, is a
      source of resistance. Herein, we investigated the role of ABCC10 in mammary
      tumours, given the important role we have defined for ABCC10 in transporting
      taxanes, and the recognition that some ABCC proteins have roles in tumour growth.
      METHODS: ABCC10 expression was correlated to human breast cancer subtype using
      breast tissue microarrays. Real-time quantitative PCR and western blot analysis
      were used to examine ABCC10 expression in human breast cancer lines. Abcc10(-/-)
      mice were crossed to MMTV-PyVmT mice to produce Abcc10(-/-) vs Abcc10(+/+)
      mammary tumours and derivative cell lines. We used allograft and cellular assays
      to perform baseline and drug sensitization analysis of tumours and cell lines.
      RESULTS: Clinical sample analyses indicated that ABCC10 was more highly expressed
      in Her2+ and ER+ than in Her2-, ER-, and triple-negative breast cancer.
      Unexpectedly, PyVmT; Abcc10(-/-) tumours grew more rapidly than PyVmT;
      Abcc10(+/+) tumours and were associated with significantly reduced apoptosis and
      metastasis. PyVmT; Abcc10(-/-) lines were less migratory than PyVmT; Abcc10(+/+)
      lines. Finally, we showed increased survival of docetaxel-treated MMTV-PyVmT;
      Abcc10(-/-) mice compared with wild-type mice. CONCLUSIONS: These data identify
      roles for Abcc10 in breast cancer pathogenesis and in vivo docetaxel resistance.

PMID- 24937673
TI  - Expression of hypoxia-inducible factor-1alpha predicts benefit from hypoxia
      modification in invasive bladder cancer.
AB  - BACKGROUND: The addition of carbogen and nicotinamide (CON) to radiotherapy (RT)
      improves overall survival in invasive bladder cancer. We explored whether
      expression of the hypoxia marker hypoxia-inducible factor-1alpha (HIF-1alpha)
      alone or in combination with other markers predicted benefit from CON. METHODS: A
      retrospective study was carried out using material from patients with high-grade
      invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or
      with CON (RT+CON). HIF-1alpha expression was studied in 137 tumours using tissue
      microarrays and immunohistochemistry. Data were available from other studies for
      carbonic anhydrase IX and glucose transporter 1 protein and gene expression and
      tumour necrosis. RESULTS: Patients with high HIF-1alpha expression had improved 5
      year local relapse-free survival with RT+CON (47%) compared with RT alone (21%;
      hazard ratio (HR) 0.48, 95% CI 0.26-0.8, P=0.02), no benefit was seen with low
      HIF-1alpha expression (HR 0.81, 95% CI 0.43-1.50, P=0.5). Combinations of markers
      including necrosis also predicted benefit but did not improve on prediction using
      necrosis alone. CONCLUSIONS: HIF-1alpha may be used to predict benefit from CON
      in patients with bladder cancer but does not improve on use of necrosis.

PMID- 24937674
TI  - Src, a potential target for overcoming trastuzumab resistance in HER2-positive
      breast carcinoma.
AB  - BACKGROUND: Src is a non-receptor tyrosine kinase involved in signalling and
      crosstalk between growth-promoting pathways. We aim to investigate the
      relationship of active Src in response to trastuzumab of HER2-positive breast
      carcinomas. METHODS: We selected 278 HER2-positive breast cancer patients with
      (n=154) and without (n=124) trastuzumab treatment. We performed
      immunohistochemistry on paraffin-embedded tissue microarrays of active Src and
      several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational
      analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were
      correlated with clinicopathological factors and patients' outcome. RESULTS:
      Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8%
      of tumours that correlated positively with tumour size, necrosis, mitosis,
      metastasis to the central nervous system, p53 overexpression and MAPK activation
      but inversely with EGFR and p27. Univariate analyses showed an association of
      increased active Src with shorter survival in patients at early stage with
      HER2/hormone receptor-negative tumours treated with trastuzumab. CONCLUSIONS: Src
      activation participates in trastuzumab mechanisms of resistance and indicates
      poor prognosis, mainly in HER2/hormone receptor-negative breast cancer.
      Therefore, blocking this axis may be beneficial in those patients.

PMID- 24937675
TI  - beta-Arrestin1 promotes the progression of chronic myeloid leukaemia by
      regulating BCR/ABL H4 acetylation.
AB  - BACKGROUND: beta-Arrestins are scaffold proteins that interact with various
      cellular signals. Although beta-arrestin2 mediates the initiation and progression
      of myeloid leukaemia, the critical role of beta-arrestin1 in the chronic myeloid
      leukaemia (CML) is still unknown. The aim of this study is to investigate the
      essential function of beta-arrestin1 in CML. METHODS: The expressions of beta
      arrestin1 and BCR/ABL in CML patients, animal models and K562 cells were measured
      by RT-PCR, immunofluorescence and western blotting. The effect of beta-arrestin1
      on CML animal models and K562 cells by colony formation, MTT and survival
      analysis were assessed. BCR/ABL H4 acetylation was analysed through the use of
      Chromatin-immunoprecipitation (ChIP) -on-chip and confirmed by ChIP respectively.
      Co-immunoprecipitation and confocal were examined for the binding of beta
      arrestin1 with enhancer of zeste homologue 2 (EZH2). RESULTS: The higher
      expression of beta-arrestin1 is positively correlated with clinical phases of CML
      patients. Depletion of beta-arrestin1 decelerates progression of K562 and primary
      cells, and increases survival of CML mice. Importantly, silenced beta-arrestin1
      results in the decrease of BCR/ABL H4 acetylation level in K562 cells. Further
      data illustrate that nuclear beta-arrestin1 binds to EZH2 to mediate BCR/ABL
      acetylation and thus regulates cell progression in K562 cells and the survival of
      CML mice. CONCLUSIONS: Our findings reveal a novel function of beta-arrestin1
      binding to EZH2 to promote CML progression by regulating BCR/ABL H4 acetylation.

PMID- 24937677
TI  - Immunological subtypes in breast cancer are prognostic for invasive ductal but
      not for invasive lobular breast carcinoma.
AB  - BACKGROUND: Classical patient and tumour characteristics are the benchmark of
      personalised breast cancer (BC) management. Recent evidence has demonstrated that
      immune and molecular profiling of BC may also play an important role. Despite
      evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they
      are infrequently accounted for when making treatment decisions for individual
      patients. The purpose of this study was to investigate the relevance of the
      tumour immune response in the major histological subtypes of BC. We also assessed
      the relationship between immune responses and molecular subtypes and their
      prognostic potential. METHODS: Immunostains were done for HLA-I, HLA-E, HLA-G,
      Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67,
      EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients
      who underwent primary surgery. RESULTS: No significant association was found
      between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and
      molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour
      immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC,
      IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was
      prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3
      or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004;
      Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible
      tumour types for either IDC or ILC. CONCLUSIONS: Tumour immune characteristics
      and host immune responses are prognostic in IDC, but not ILC. In addition, tumour
      immune profiles are only prognostic in Luminal A tumours.

PMID- 24937676
TI  - Strategies to diagnose ovarian cancer: new evidence from phase 3 of the
      multicentre international IOTA study.
AB  - BACKGROUND: To compare different ultrasound-based international ovarian tumour
      analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer
      diagnosis using a meta-analysis approach of centre-specific data from IOTA3.
      METHODS: This prospective multicentre diagnostic accuracy study included 2403
      patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012.
      All patients underwent standardised transvaginal ultrasonography. Test
      performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA
      risk models (LR1 and LR2), and strategies involving combinations of IOTA simple
      rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated
      using a meta-analysis approach. Reference standard was histology after surgery.
      RESULTS: The areas under the receiver operator characteristic curves of LR1, LR2,
      SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and
      0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2,
      SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79%
      and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded
      equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index
      had sensitivity 67%, specificity 91% and DOR 17.5. CONCLUSIONS: This study shows
      all IOTA strategies had excellent diagnostic performance in comparison with RMI.
      The IOTA strategy chosen may be determined by clinical preference.

PMID- 24937679
TI  - Coupling isotachophoresis with affinity chromatography for rapid and selective
      purification with high column utilization, part 1: theory.
AB  - We present a novel technique that couples isotachophoresis (ITP) with affinity
      chromatography (AC) to achieve rapid, selective purification with high column
      utilization. ITP simultaneously preconcentrates an analyte and purifies it, based
      on differences in mobility of sample components, excluding species that may foul
      or compete with the target at the affinity substrate. ITP preconcentration
      accelerates the affinity reaction, reducing assay time, improving column
      utilization, and allowing for capture of targets with higher dissociation
      constants. Furthermore, ITP-AC separates the target and contaminants into
      nondiffusing zones, thus achieving high resolution in a short distance and time.
      We present an analytical model for spatiotemporal dynamics of ITP-AC. We identify
      and explore the effect of key process parameters, including target distribution
      width and height, ITP zone velocity, forward and reverse reaction constants, and
      probe concentration on necessary affinity region length, assay time, and capture
      efficiency. Our analytical approach shows collapse of these variables to three
      nondimensional parameters. The analysis yields simple analytical relations for
      capture length and capture time in relevant ITP-AC regimes, and it demonstrates
      how ITP greatly reduces assay time and improves column utilization. In the second
      part of this two-part series, we will present experimental validation of our
      model and demonstrate ITP-AC separation of the target from 10,000-fold more
      abundant contaminants. 

PMID- 24937678
TI  - Nucleophilic 1,4-additions for natural product discovery.
AB  - Natural products remain an important source of drug candidates, but the
      difficulties inherent to traditional isolation, coupled with unacceptably high
      rates of compound rediscovery, limit the pace of natural product detection. Here
      we describe a reactivity-based screening method to rapidly identify exported
      bacterial metabolites that contain dehydrated amino acids (i.e., carbonyl- or
      imine-activated alkenes), a common motif in several classes of natural products.
      Our strategy entails the use of a commercially available thiol, dithiothreitol,
      for the covalent labeling of activated alkenes by nucleophilic 1,4-addition.
      Modification is easily discerned by comparing mass spectra of reacted and
      unreacted cell surface extracts. When combined with bioinformatic analysis of
      putative natural product gene clusters, targeted screening and isolation can be
      performed on a prioritized list of strains. Moreover, known compounds are easily
      dereplicated, effectively eliminating superfluous isolation and characterization.
      As a proof of principle, this labeling method was used to identify known natural
      products belonging to the thiopeptide, lanthipeptide, and linaridin classes.
      Further, upon screening a panel of only 23 actinomycetes, we discovered and
      characterized a novel thiopeptide antibiotic, cyclothiazomycin C. 

PMID- 24937680
TI  - Inpatient coronary angiography and revascularisation following non-ST-elevation
      acute coronary syndrome in patients with renal impairment: a cohort study using
      the Myocardial Ischaemia National Audit Project.
AB  - BACKGROUND: International guidelines support an early invasive management
      strategy (including early coronary angiography and revascularisation) for non-ST
      elevation acute coronary syndrome (NSTE-ACS) in patients with renal impairment.
      However, evidence from outside the UK suggests that this approach is
      underutilised. We aimed to describe practice within the NHS, and to determine
      whether the severity of renal dysfunction influenced the provision of angiography
      and modified the association between early revascularisation and survival.
      METHODS: We performed a cohort study, using multivariable logistic regression and
      propensity score analyses, of data from the Myocardial Ischaemia National Audit
      Project for patients presenting with NSTE-ACS to English or Welsh hospitals
      between 2008 and 2010. FINDINGS: Of 35 881 patients diagnosed with NSTE-ACS, eGFR
      of <60 ml/minute/1.73 m(2) was present in 15 680 (43.7%). There was a stepwise
      decline in the odds of undergoing inpatient angiography with worsening renal
      dysfunction. Compared with an eGFR>90 ml/minute/1.73 m(2), patients with an eGFR
      between 45-59 ml/minute/1.73 m(2) were 33% less likely to undergo angiography
      (adjusted OR 0.67, 95% CI 0.55-0.81); those with an eGFR<30/minute/1.73 m(2) had
      a 64% reduction in odds of undergoing angiography (adjusted OR 0.36, 95%CI 0.29
      0.43). Of 16 646 patients who had inpatient coronary angiography, 58.5% underwent
      inpatient revascularisation. After adjusting for co-variables, inpatient
      revascularisation was associated with approximately a 30% reduction in death
      within 1 year compared with those managed medically after coronary angiography
      (adjusted OR 0.66, 95%CI 0.57-0.77), with no evidence of modification by renal
      function (p(interaction) = 0.744). INTERPRETATION: Early revascularisation may
      offer a similar survival benefit in patients with and without renal dysfunction,
      yet renal impairment is an important determinant of the provision of coronary
      angiography following NSTE-ACS. A randomised controlled trial is needed to
      evaluate the efficacy of an early invasive approach in patients with severe renal
      dysfunction to ensure that all patients who may benefit are offered this
      treatment option.

PMID- 24937681
TI  - Rh(I)-catalyzed intermolecular hydroacylation: enantioselective cross-coupling of
      aldehydes and ketoamides.
AB  - Under Rh(I) catalysis, alpha-ketoamides undergo intermolecular hydroacylation
      with aliphatic aldehydes. A newly designed Josiphos ligand enables access to
      alpha-acyloxyamides with high atom-economy and enantioselectivity. On the basis
      of mechanistic and kinetic studies, we propose a pathway in which rhodium plays a
      dual role in activating the aldehyde for cross-coupling. A stereochemical model
      is provided to rationalize the sense of enantioinduction observed. 

PMID- 24937683
TI  - Particle-nested inverse opal structures as hierarchically structured large-scale
      membranes with tunable separation properties.
AB  - A novel multiscale porous architecture where an individual particle is nested
      inside a hollow chamber of inverse-opal (IO) frame is created using a large scale
      self-assembly of core-shell structured colloidal particles and subsequent
      selective removal of the outer shells of the colloids. Since the nested particle
      is smaller than the size of individual IO chamber, the interconnected
      nanochannels are spontaneously formed within the structured frame. The size of
      internal nanochannels is readily tuned to have high permeability and size
      selective separation capability, which is successfully tested for nanoparticle
      separation. 

PMID- 24937682
TI  - Supramolecular disassembly of facially amphiphilic dendrimer assemblies in
      response to physical, chemical, and biological stimuli.
AB  - CONSPECTUS: Supramolecular assemblies formed from spontaneous self-assembly of
      amphiphilic macromolecules are explored as biomimetic architectures and for
      applications in areas such as sensing, drug delivery, and diagnostics.
      Macromolecular assemblies are usually preferred, compared with their simpler
      small molecule counterparts, due to their low critical aggregate concentrations
      (CAC) and high thermodynamic stability. This Account focuses on the structural
      and functional aspects of assemblies formed from dendrimers, specifically
      facially amphiphilic dendrons that form micelle or inverse micelle type
      supramolecular assemblies depending on the nature of the solvent medium. The
      micelle type assemblies formed from facially amphiphilic dendrons sequester
      hydrophobic guest molecules in their interiors. The stability of these assemblies
      is dependent on the relative compatibility of the hydrophilic and hydrophobic
      functionalities with water, often referred to as hydrophilic-lipophilic balance
      (HLB). Disruption of the HLB, using an external stimulus, could lead to
      disassembly of the aggregates, which can then be utilized to cause an actuation
      event, such as guest molecule release. Studying these possibilities has led to
      (i) a robust and general strategy for stimulus-induced disassembly and molecular
      release and (ii) the introduction of a new approach to protein-responsive
      supramolecular disassembly. The latter strategy provides a particularly novel
      avenue for impacting biomedical applications. Most of the stimuli-sensitive
      supramolecular assemblies have been designed to be responsive to factors such pH,
      temperature, and redox conditions. The reason for this interest stems from the
      fact that certain disease microenvironments have aberrations in these factors.
      However, these variations are the secondary imbalances in biology. Imbalances in
      protein activity are the primary reasons for most, if not all, human pathology.
      There have been no robust strategies in stimulus-responsive assemblies that
      respond to these variations. The facially amphiphilic dendrimers provide a unique
      opportunity to explore this possibility. Similarly, the propensity of these
      molecules to form inverse micelles in apolar solvents and thus bind polar guest
      molecules, combined with the fact that these assemblies do not thermodynamically
      equilibrate in biphasic mixtures, was used to predictably simplify peptide
      mixtures. The structure-property relationships developed from these studies have
      led to a selective and highly sensitive detection of peptides in complex
      mixtures. Selectivity in peptide extraction was achieved using charge
      complementarity between the peptides and the hydrophilic components present in
      inverse micellar interiors. These findings will have implications in areas such
      as proteomics and biomarker detection.

PMID- 24937684
TI  - High-salt intake suppressed microRNA-133a expression in Dahl SS rat myocardium.
AB  - Salt-sensitive individuals show earlier and more serious cardiac damage than
      nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could
      reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to
      investigate the different functions of high-salt intake on salt-sensitive (SS)
      rats and Sprague-Dawley (SD) rats and the involvement of microRNA-133a in these
      roles. After high-salt intervention, the left ventricular mass (LVW) and left
      ventricular mass index (LVMI) of the salt-sensitive high salt (SHS) group were
      obviously higher than those of the salt-sensitive low salt (SLS) group. However,
      the difference between the Sprague-Dawley high salt (DHS) group and the Sprague
      Dawley low salt (DLS) group was not significant. Compared with SLS group,
      collagen I and connective tissue growth factor (CTGF) in the heart of SHS group
      were significantly higher, whereas no statistical difference was observed between
      the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in
      the heart of both strains were significantly decreased, but that in the SHS group
      decreased more significantly. These results suggest that high salt intervention
      could down-regulate the expression of myocardial microRNA-133a, which may be one
      of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension.

PMID- 24937686
TI  - Continuous flow atmospheric pressure laser desorption/ionization using a 6-7-um
      band mid-infrared tunable laser for biomolecular mass spectrometry.
AB  - A continuous flow atmospheric pressure laser desorption/ionization technique
      using a porous stainless steel probe and a 6-7-um-band mid-infrared tunable laser
      was developed. This ion source is capable of direct ionization from a continuous
      flow with a high temporal stability. The 6-7-um wavelength region corresponds to
      the characteristic absorption bands of various molecular vibration modes,
      including O-H, C=O, CH3 and C-N bonds. Consequently, many organic compounds and
      solvents, including water, have characteristic absorption peaks in this region.
      This ion source requires no additional matrix, and utilizes water or acetonitrile
      as the solvent matrix at several absorption peak wavelengths (6.05 and 7.27 um,
      respectively). The distribution of multiply-charged peptide ions is extremely
      sensitive to the temperature of the heated capillary, which is the inlet of the
      mass spectrometer. This ionization technique has potential for the interface of
      liquid chromatography/mass spectrometry (LC/MS). 

PMID- 24937685
TI  - Metabolic profiling of somatic tissues from Monochamus alternatus (Coleoptera:
      Cerambycidae) reveals effects of irradiation on metabolism.
AB  - A high-level of sexual sterility is of importance for the sterile insect
      technique (SIT). However, the use of high-dose-intensity gamma radiation to
      induce sterility has negative impacts not only on reproductive cells but also on
      somatic cells. In this study, we investigated the metabolite differences in
      somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated
      male Monochamus alternatus, an important vector of the pathogenic nematode,
      Bursaphelenchus xylophilus, which kills Asian pines. The results showed that
      metabolite levels changed moderately in the 20-Gy samples but were markedly
      altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six
      and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively.
      Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but
      were not changed significantly in the 20-Gy samples. The comprehensive
      metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic
      pathways involved in the life process. The findings presented in this manuscript
      will contribute to our knowledge of the characteristic metabolic changes
      associated with gamma-radiation-induced damage to somatic cells and will allow
      for better exploration of the SIT for the control of this target pest. 

PMID- 24937687
TI  - Comparisons of non-Gaussian statistical models in DNA methylation analysis.
AB  - As a key regulatory mechanism of gene expression, DNA methylation patterns are
      widely altered in many complex genetic diseases, including cancer. DNA
      methylation is naturally quantified by bounded support data; therefore, it is non
      Gaussian distributed. In order to capture such properties, we introduce some non
      Gaussian statistical models to perform dimension reduction on DNA methylation
      data. Afterwards, non-Gaussian statistical model-based unsupervised clustering
      strategies are applied to cluster the data. Comparisons and analysis of different
      dimension reduction strategies and unsupervised clustering methods are presented.
      Experimental results show that the non-Gaussian statistical model-based methods
      are superior to the conventional Gaussian distribution-based method. They are
      meaningful tools for DNA methylation analysis. Moreover, among several non
      Gaussian methods, the one that captures the bounded nature of DNA methylation
      data reveals the best clustering performance. 

PMID- 24937688
TI  - Bacterial cellulose membranes used as artificial substitutes for dural defection
      in rabbits.
AB  - To improve the efficacy and safety of dural repair in neurosurgical procedures, a
      new dural material derived from bacterial cellulose (BC) was evaluated in a
      rabbit model with dural defects. We prepared artificial dura mater using
      bacterial cellulose which was incubated and fermented from Acetobacter xylinum.
      The dural defects of the rabbit model were repaired with BC membranes. All
      surgeries were performed under sodium pentobarbital anesthesia, and all efforts
      were made to minimize suffering. All animals were humanely euthanized by
      intravenous injection of phenobarbitone, at each time point, after the operation.
      Then, the histocompatibility and inflammatory effects of BC were examined by
      histological examination, real-time fluorescent quantitative polymerase chain
      reaction (PCR) and Western Blot. BC membranes evenly covered the surface of brain
      without adhesion. There were seldom inflammatory cells surrounding the membrane
      during the early postoperative period. The expression of inflammatory cytokines
      IL-1beta, IL-6 and TNF-alpha as well as iNOS and COX-2 were lower in the BC group
      compared to the control group at 7, 14 and 21 days after implantation. BC can
      repair dural defects in rabbit and has a decreased inflammatory response compared
      to traditional materials. However, the long-term effects need to be validated in
      larger animals. 

PMID- 24937689
TI  - Bridged tolanes: a twisted tale.
AB  - The rotational motion of tolanes along their acetylene axis is not fully
      understood. What happens to the optical and electronic properties if the tolane
      backbone is forced into a twisted conformation? Several tethers were investigated
      to obtain tolanophanes, fixing the torsion angle of the two phenyl rings. X-ray
      crystal structures revealed tether-specific torsion angles in the solid state.
      The absorption, emission, and excitation spectra were recorded. Twisted tethered
      tolane conformers showed blue-shifted absorption; emission spectra were all
      torsionally independent and identical. The tethered tolanes were embedded in a
      rigid matrix by freezing to 77 K; well-resolved emission spectra were recorded
      for planar tolanes, but for twisted systems unexpectedly long-lived
      phosphorescence was observed. How is this triplet emission explained? Quantum
      chemical calculations (TDDFT/cam-B3LYP/6-31G*) of the unsubstituted tolane showed
      that intersystem crossing (ISC) is favored with large spin-orbit coupling, which
      occurs when the molecular orbitals are orthogonal to each other; this is the case
      at the crossing of S1/T7. Also, a small energy difference between singlet and
      triplet states is required; we found that ISC can favorably take place at four
      crossings: S1/T6, S1/T7, S1/T(8,9), S1/T10.

PMID- 24937690
TI  - Characterization of prostate lesions as benign or malignant at multiparametric MR
      imaging: comparison of three scoring systems in patients treated with radical
      prostatectomy.
AB  - PURPOSE: To compare the subjective Likert score to the Prostate Imaging Reporting
      and Data System (PIRADS) and morphology-location-signal intensity (MLS) scores
      for categorization of prostate lesions as benign or malignant at multiparametric
      magnetic resonance (MR) imaging. MATERIALS AND METHODS: Two hundred fifteen
      patients who underwent T2-weighted, diffusion-weighted, and dynamic contrast
      material-enhanced multiparametric MR imaging of the prostate before radical
      prostatectomy were included in a prospective database after they signed the
      institutional review board-approved forms. Senior readers 1 and 2 prospectively
      noted the location, shape, and signal intensity of lesions on MR images from
      individual pulse sequences and scored each for likelihood of malignancy by using
      a Likert scale (range, 1-5). A junior reader (reader 3) retrospectively reviewed
      the database and did the same analysis. The MLS score (range, 1-13) was computed
      by using the readers' descriptions of the lesions. Then, the three readers again
      scored the lesions they described by using the PIRADS score (range, 3-15). MLS
      and PIRADS scores were compared with the Likert score by using their areas under
      the receiver operating characteristic curves. RESULTS: Areas under the receiver
      operating characteristic curves of the Likert, MLS, and PIRADS scores were 0.81,
      0.77 (P = .03), and 0.75 (P = .01) for reader 1; 0.88, 0.74 (P < .0001), and 0.76
      (P < .0001) for reader 2; and 0.81, 0.78 (P = .23), and 0.75 (P = .01) for reader
      3. For diagnosing cancers with Gleason scores greater than or equal to 7, the
      Likert score was significantly more accurate than the others, except for the MLS
      score for reader 3. Weighted kappa values were 0.470-0.524, 0.405-0.430, and
      0.378-0.441 for the Likert, MLS, and PIRADS scores, respectively. CONCLUSION: The
      Likert score allowed significantly more accurate categorization of prostate
      lesions on MR images than did the MLS and PIRADS scores.

PMID- 24937691
TI  - Contralateral prophylactic mastectomy in the American College of Radiology
      Imaging Network 6667 trial: effect of breast MR imaging assessments and patient
      characteristics.
AB  - PURPOSE: To assess which patient and magnetic resonance (MR) imaging factors are
      associated with the likelihood of contralateral prophylactic mastectomy (CPM) in
      patients with newly diagnosed breast cancer. MATERIALS AND METHODS: The American
      College of Radiology Imaging Network 6667 trial was compliant with HIPAA;
      institutional review board approval was obtained at each site. All patients
      provided written informed consent. This study was a retrospective review of data
      from 934 women enrolled in the trial who did not have a known contralateral
      breast cancer at the time of surgical planning. The authors assessed age,
      menopausal status, index breast cancer histologic results, contralateral breast
      histologic results, breast density, family history, race and/or ethnicity, MR
      imaging Breast Imaging Reporting and Data System (BI-RADS) assessment, and number
      of MR imaging lesions for association with CPM by using the Fisher exact test,
      exact chi(2) test, and multivariate logistic regression analyses. RESULTS: Eighty
      six of the 934 (9.2%) women underwent CPM and were more likely to be younger
      (mean age, 48 years [range, 27-78 years] vs mean age, 54 years [range, 25-86
      years]; P < .0001), be premenopausal (55 of 86 [64%] vs 349 of 845 [41%], P <
      .0001), have ductal carcinoma in situ (DCIS) in the index breast (31% [27 of 86]
      vs 19% [164 of 848], P = .02), have greater breast density (71 of 86 [83%] vs 572
      of 848 [68%], P = .004), and have a family history of breast cancer (44 of 86
      [30%] vs 150 of 488 [18%], P = .01) than those who did not undergo CPM.
      Distributions of race and/or ethnicity, contralateral lesion pathologic results,
      and number of MR imaging lesions were similar in both groups. With multivariate
      modeling, younger age, greater breast density, DCIS index cancer, and family
      history remained significant, whereas menopausal status did not. Positive MR
      imaging assessments were not significantly more frequent in the CPM group than in
      the group of women who did not undergo CPM (14 of 86 [16.3%] vs 113 of 848
      [13.3%], P = .43). CONCLUSION: In patients with newly diagnosed breast cancer who
      underwent breast MR imaging at which a contralateral breast cancer was not
      identified, patient factors and not breast MR imaging BI-RADS scores were chief
      determinants in decisions regarding CPM. Online supplemental material is
      available for this article.

PMID- 24937693
TI  - Estimates of effective dose for CT scans of the lower extremities.
AB  - PURPOSE: To determine the dose-length product (DLP)-effective dose (ED) (DLP/ED)
      conversion coefficient (k) tables for the lower extremities that can be used for
      calculating ED. MATERIALS AND METHODS: Dose calculations were performed on
      standard phantoms using a validated Monte Carlo calculation tool. Calculations
      were performed to obtain ED values for tube voltages from 80 kV to 140 kV in
      steps of 20 kV for the following examinations: hip (femur), knee, ankle, and
      computed tomographic (CT) angiography of the lower extremities. Values of the DLP
      were calculated by multiplying measured CT dose index values by the scan length;
      k values resulted as the quotients of the ED and DLP values. DLP/ED coefficients
      averaged over the range of voltage values and their standard deviations were
      determined for the given lower-extremity CT examinations for all age groups and
      for both sexes. RESULTS: Coefficients depend strongly on the phantom age and
      size, but little on the kilovolt value. In the case of the newborn, for example,
      k values were 0.0612, 0.0046, 0.0014, and 0.047 for hip, knee, ankle, and CT
      angiography, respectively, while in the case of the adult, these respective
      values were 0.0110, 0.0004, 0.0002, and 0.0062. A substantial difference up to
      20% between coefficients in male and female phantoms was observed for CT
      angiographic examination. CONCLUSION: DLP/ED conversion coefficients are provided
      for lower extremities and allow estimation of ED for commonly used clinical
      musculoskeletal CT and CT angiographic protocols.

PMID- 24937692
TI  - Assessment of regional lung function with multivolume (1)H MR imaging in health
      and obstructive lung disease: comparison with (3)He MR imaging.
AB  - PURPOSE: To introduce a method based on multivolume proton (hydrogen [(1)H])
      magnetic resonance (MR) imaging for the regional assessment of lung ventilatory
      function, investigating its use in healthy volunteers and patients with
      obstructive lung disease and comparing the outcome with the outcome of the
      research standard helium 3 ((3)He) MR imaging. MATERIALS AND METHODS: The
      institutional review board approved the HIPAA-compliant protocol, and informed
      written consent was obtained from each subject. Twenty-six subjects, including
      healthy volunteers (n = 6) and patients with severe asthma (n = 11) and mild (n =
      6) and severe (n = 3) emphysema, were imaged with a 1.5-T whole-body MR unit at
      four lung volumes (residual volume [ RV residual volume ], functional residual
      capacity [ FRC functional residual capacity ], 1 L above FRC functional residual
      capacity [ FRC+1 L 1 L above FRC ], total lung capacity [ TLC total lung capacity
      ]) with breath holds of 10-11 seconds, by using volumetric interpolated breath
      hold examination. Each pair of volumes were registered, resulting in maps of (1)H
      signal change between the two lung volumes. (3)He MR imaging was performed at
      FRC+1 L 1 L above FRC by using a two-dimensional gradient-echo sequence. (1)H
      signal change and (3)He signal were measured and compared in corresponding
      regions of interest selected in ventral, intermediate, and dorsal areas. RESULTS:
      In all volunteers and patients combined, proton signal difference between TLC
      total lung capacity and RV residual volume correlated positively with (3)He
      signal (correlation coefficient R(2) = 0.64, P < .001). Lower (P < .001) but
      positive correlation results from (1)H signal difference between FRC functional
      residual capacity and FRC+1 L 1 L above FRC (R(2) = 0.44, P < .001). In healthy
      volunteers, (1)H signal changes show a higher median and interquartile range
      compared with patients with obstructive disease and significant differences
      between nondependent and dependent regions. CONCLUSION: Findings in this study
      demonstrate that multivolume (1)H MR imaging, without contrast material, can be
      used as a biomarker for regional ventilation, both in healthy volunteers and
      patients with obstructive lung disease.

PMID- 24937695
TI  - SOX2 enhances the migration and invasion of ovarian cancer cells via Src kinase.
AB  - Ovarian cancer is the leading cause of death among gynecologic cancers and is the
      fifth leading cause of all cancer-related deaths among women. The development of
      novel molecular targets is therefore important to many patients. Recently, the
      SRY-related transcription factor SOX2 has been widely reported to be involved in
      multiple pathophysiological diseases, including maintenance of stem cell
      characteristics and carcinogenesis. Up to now, SOX2 has been mainly shown to
      promote the development of cancer, although its inhibitory roles in cancer have
      also been reported. However, the role of SOX2 in ovarian cancer is largely
      unknown. In the present study, we detected the expression of SOX2 in 64 human
      serous ovarian carcinoma (SOC) tissues and paired corresponding metastatic
      specimens using immunohistochemistry. The results showed that the expression of
      SOX2 in primary tumors is much lower than that in the corresponding metastatic
      lesions. We further found that SOX2 overexpression promotes proliferation,
      migration and invasion, while inhibiting adhesion abilities of SOC cells.
      Finally, we found that SOX2 targets Src kinase, a non-receptor tyrosine kinase
      that regulates cell migration, invasion and adhesion in SOC cells. Together,
      these results suggested that Src kinase is a key molecule in SOX2-mediated
      migration and invasion of SOC cells. 

PMID- 24937696
TI  - Female sexual dysfunction in patients with spinal cord injury: a study from Iran.
AB  - OBJECTIVES: We assess the prevalence of sexual dysfunction in patients with
      spinal cord injury (SCI), compare sexual function and sexual distress between
      female patients with SCI and gender-matched healthy controls, and address risk
      factors associated with sexual dysfunction among Iranian female patients with
      SCI. SETTING: Brain and Spinal Cord Injury Research Center, Neuroscience
      Institute, Tehran University of Medical Sciences, Tehran, Iran. METHODS: Eligible
      Iranian female patients with SCI were included in this cross-sectional study.
      They were asked to provide sociodemographic information, and complete the Female
      Sexual Function Index, Hospital Anxiety and Depression Scale and Female Sexual
      Distress Scale-Revised questionnaire. RESULTS: Of the 105 patients participated
      in this study, the average age was 41.0 (s.d.=10.1) years. Women with SCI
      reported significantly higher levels of sexual dysfunction compared with normal
      controls. Approximately, 88% of SCI patients reported at least one type of sexual
      dysfunction, whereas only 37% of healthy controls reported sexual dysfunction.
      Lack of vaginal lubrication was reported more frequent in SCI patients compared
      with controls. Women with SCI reported a significantly higher level of sexual
      distress compared with healthy women. Sexual dysfunction was observed to be
      significantly higher in older patients, those with less education, patients with
      complete lesions, those with sexual distress and patients who were anxious and
      depressed. CONCLUSION: Sexual dysfunction is highly prevalent among Iranian women
      with SCI. Sexual dysfunction is associated with age, education, symptoms of
      depression and anxiety and level of injury. Sexual counseling during the
      rehabilitation period may help to prevent sexual dysfunction following SCI.

PMID- 24937697
TI  - Participation in sport in persons with spinal cord injury in Switzerland.
AB  - STUDY DESIGN: Secondary data analysis of a questionnaire-based, cross-sectional
      survey in persons with spinal cord injury (SCI) in Switzerland. OBJECTIVE: To
      describe the frequency of participation in sport (PiS) and to identify correlates
      for PiS in persons with SCI in Switzerland. SETTING: Community
      sampleMethods:Frequency of PiS was assessed retrospectively for the time before
      the onset of SCI and the time of the survey using a single-item question. A
      comprehensive set of independent variables was selected from the original
      questionnaire. Descriptive statistics, bivariate analyses and ordinal regressions
      were carried out. RESULTS: Data from 505 participants were analyzed. Twenty
      independent variables were selected for analyses. PiS decreased significantly
      from the time before the onset of SCI to the time of the survey (P<0.001). Sport
      levels were significantly lower in women than men for the time of the survey
      (P<0.001), whereas no difference was observed before onset of SCI (P=0.446).
      Persons with tetraplegia participated significantly less often in sport than
      persons with paraplegia (P<0.001). Lesion level, active membership in a club,
      frequency of PiS before the onset of SCI and the subjective evaluation of the
      importance of sport correlate with PiS. When controlling for gender differences,
      only the subjective importance of sport for persons with SCI determines PiS,
      particularly among women. CONCLUSIONS: Persons with tetraplegia and women need
      special attention when planning interventions to improve PiS. Furthermore, the
      subjective importance of sport is important for PiS, particularly among women,
      whereas most other factors were only weakly associated with PiS.

PMID- 24937698
TI  - Spinal cord injury in older population in Turkey.
AB  - STUDY DESIGN: Retrospective, comparative 4-year study. OBJECTIVES: To identify
      the clinical characteristics unique to older patients with spinal cord injury
      (SCI). SETTING: Turkish Armed Forces Rehabilitation Center, Ankara, Turkey.
      METHODS: The study included 870 consecutive patients with SCI that were divided
      into two groups according to age. Patients aged ?60 years at the time of injury
      constituted the study group, and randomly selected patients aged <60 years that
      were matched for gender, week of admission and time since injury constituted the
      control group. Patients' demographic and clinical characteristics were recorded,
      compared and analyzed. RESULTS: The study group included 73 SCI patients (mean
      age: 66.98+/-6.28 years) and the control group included 75 SCI patients (mean
      age: 33.93+/-10.67 years). Among the 148 patients, 98 (66.2%) were male. The vast
      majority of lesions were at the thoracic level (47.3%). In the older group, falls
      were the most frequent etiology (32.9%), simple falls predominated (62.5%). 49.3%
      of the study group vs 18.6% of the control group had a non-traumatic cause of
      SCI. Older patients were found to be less likely to have complete injury (27.4 vs
      44%, P=0.035). The most common bladder management method was intermittent
      catheterization (69.6%) and the number of patients in each group treated with
      this method did not differ significantly (P>0.05). More patients in the study
      group had neuropathic pain (50.7 vs 34.7%, P=0.049) and abnormal urinary
      ultrasound findings (23.3 vs 9.3%, P=0.021). CONCLUSION: RESULTS revealed that
      older patients with SCI may have different demographic and clinical features
      compared with younger patients.

PMID- 24937699
TI  - Using Rasch motor FIM individual growth curves to inform clinical decisions for
      persons with paraplegia.
AB  - STUDY DESIGN: A longitudinal retrospective study. OBJECTIVE: To better understand
      individual-level temporal change in functional status for participants with
      paraplegia in the National Spinal Cord Injury Database (NSCID), as measured by
      Rasch Transformed Motor Functional Indepedence Measure (FIM) scores. SETTING:
      Multicenter/Multistate longitudinal study across the United States. METHODS: Non
      linear random effects modeling, that is, individual growth curve analysis of
      retrospective data obtained from the National Institute on Disability and
      Rehabilitation Research (NIDRR) NSCID. RESULTS: We generated non-linear
      individual level trajectories of recovery for Rasch Transformed Motor FIM scores
      that rise rapidly from inpatient rehabilitation admission to a plateau.
      Trajectories are based on relationships between growth parameters and patient and
      injury factors: race, gender, level of education at admission, age at injury,
      neurological level at discharge, American Spinal Injury Association Impairment
      Scale (AIS) at discharge, days from injury to first system inpatient
      rehabilitation admission, rehabilitation length of stay, marital status and
      etiology. On the basis of study results, an interactive tool was developed to
      represent individual level longitudinal outcomes as trajectories based upon an
      individual's given baseline characteristics, that is, information supplied by the
      covariates and provides a robust description of temporal change for those with
      paraplegia within the NSCID. CONCLUSIONS: This methodology allows researchers and
      clinicians to generate and better understand patient-specific trajectories
      through the use of an automated interactive tool where a nearly countless number
      of longitudinal paths of recovery can be explored. Projected trajectories holds
      promise in facilitating planning for inpatient and outpatient services, which
      could positively impact long term outcomes.

PMID- 24937701
TI  - Comprehensive overview of the structure and regulation of the glucocorticoid
      receptor.
AB  - Glucocorticoids are among the most prescribed drugs worldwide for the treatment
      of numerous immune and inflammatory disorders. They exert their actions by
      binding to the glucocorticoid receptor (GR), a member of the nuclear receptor
      superfamily. There are several GR isoforms resulting from alternative RNA
      splicing and translation initiation of the GR transcript. Additionally, these
      isoforms are all subject to several transcriptional, post-transcriptional, and
      post-translational modifications, all of which affect the protein's stability
      and/or function. In this review, we summarize recent knowledge on the distinct GR
      isoforms and the processes that generate them. We also review the importance of
      all known transcriptional, post-transcriptional, and post-translational
      modifications, including the regulation of GR by microRNAs. Moreover, we discuss
      the crucial role of the putative GR-bound DNA sequence as an allosteric ligand
      influencing GR structure and activity. Finally, we describe how the differential
      composition and distinct regulation at multiple levels of different GR species
      could account for the wide and diverse effects of glucocorticoids. 

PMID- 24937700
TI  - Electromechanical abdominal massage and colonic function in individuals with a
      spinal cord injury and chronic bowel problems.
AB  - STUDY DESIGN: A prospective intervention of noninvasive abdominal massage using
      an electromechanical apparatus on bowel function in individuals with spinal cord
      injury (SCI). OBJECTIVES: To evaluate the effects of noninvasive abdominal
      massage using an electromechanical apparatus on bowel function in individuals
      with SCI and chronic bowel problems. This easy-to-use apparatus can be applied by
      the patients at home without the help of a therapist. SETTING: Homes of community
      living individuals. METHODS: Twenty-one subjects with SCI were instructed to use
      the massage apparatus daily for 20 min during a 10-week period. Compliance,
      effects, side effects and user satisfaction were assessed using questionnaires.
      RESULTS: Fifteen subjects completed the 10-week period. Although some
      characteristics of defecation changed positively for some of the subjects (time
      to result, amount, consistency), none felt better or more confident after using
      the massage device. In addition, some individuals experienced negative side
      effects (predominantly pain or discomfort). The overall satisfaction with the
      device is ambiguous, with half of the group judging the device as insufficient
      and the other half as at least adequate. CONCLUSION: The use of an
      electromechanical massage device does not improve bowel function in most
      individuals with SCI who have chronic bowel problems. Why some subjects benefit
      and others do not should be investigated in future studies.

PMID- 24937704
TI  - Mechanism of fast pyrolysis of lignin: studying model compounds.
AB  - Fast pyrolysis of lignin is one of the most promising methods to convert the
      complex and irregular structure of lignin into renewable chemicals and fuel.
      During pyrolysis the complex set of radical reactions, rearrangements, and
      eliminations is influenced by temperature, pressure, and the lignin origin and
      structure. This model compound study aims to understand reaction pathways and how
      primary intermediates lead to the observed product selectivity. The pyrolysis
      microreactor directly connected to the gas chromatograph with a mass spectrometer
      (py-GC/MS) detects the final products, while imaging photoelectron photoion
      coincidence (iPEPICO) with VUV synchrotron radiation shows primary decomposition
      radicals. The tested model compounds, diphenylether (DPE) and ortho-methoxyphenol
      (guaiacol), represent a common lignin linkage and the most present subunit in
      lignin, respectively. Radical fragments, such as the hydroxycyclopentadienyl
      radical in guaiacol decomposition, are identified by mass-selected threshold
      photoelectron spectra (ms-TPES) in excellent agreement with the Franck-Condon
      simulation. While homolysis produces phenoxy-, phenyl-, and hydroxyphenoxy
      radicals, which are observed in high vacuum, radically initiated reactions are
      dominant in ambient conditions and produce recombination and rearrangement
      products, such as 2-hydroxybenzaldehyde in the case of guaiacol. The degree of
      substitution plays a dominant role in both the stabilization of the intermediate
      radical and the following degree of recombination. The recombination of phenoxy
      radicals is enhanced compared to hydroxy-phenoxy radicals. 

PMID- 24937702
TI  - Motesanib (AMG706), a potent multikinase inhibitor, antagonizes multidrug
      resistance by inhibiting the efflux activity of the ABCB1.
AB  - Cancer cells often become resistant to chemotherapy through a phenomenon known as
      multidrug resistance (MDR). Several factors are responsible for the development
      of MDR, preeminent among them being the accelerated drug efflux mediated by
      overexpression of ATP binding cassette (ABC) transporters. Some small molecule
      tyrosine kinase inhibitors (TKIs) were recently reported to modulate the activity
      of ABC transporters. Therefore, the purpose of this study was to determine if
      motesanib, a multikinase inhibitor, could reverse ABCB1-mediated MDR. The results
      showed that motesanib significantly sensitized both ABCB1-transfected and drug
      selected cell lines overexpressing this transporter to its substrate anticancer
      drugs. Motesanib significantly increased the accumulation of [(3)H]-paclitaxel in
      ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter.
      In contrast, no significant change in the expression levels and localization
      pattern of ABCB1 was observed when ABCB1 overexpressing cells were exposed to
      3MUM motesanib for 72h. Moreover, motesanib stimulated the ATPase activity of
      ABCB1 in a concentration-dependent manner, indicating a direct interaction with
      the transporter. Consistent with these findings, the docking studies indicated
      favorable binding of motesanib within the transmembrane region of homology
      modeled human ABCB1. Here, we report for the first time, motesanib, at clinically
      achievable plasma concentrations, antagonizes MDR by inhibiting the efflux
      activity of the ABCB1 transporter. These findings may be useful for cancer
      combination therapy with TKIs in the clinic. 

PMID- 24937703
TI  - Lp(a) is not associated with diabetes but affects fibrinolysis and clot structure
      ex vivo.
AB  - Lipoprotein (a) [Lp(a)] is a low density lipoprotein (LDL) with one
      apolipoprotein (a) molecule bound to the apolipoprotein B-100 of LDL. Lp(a) is an
      independent risk factor for cardiovascular disease (CVD). However, the
      relationship of Lp(a) to diabetes and metabolic syndrome, both known for
      increased CVD risk, is controversial. In a population based study on type two
      diabetes mellitus (T2DM) development in women, Lp(a) plasma levels showed the
      well known skewed distribution without any relation to diabetes or impaired
      glucose tolerance. A modified clot lysis assay on a subset of 274 subjects showed
      significantly increased clot lysis times in T2DM subjects, despite inhibition of
      PAI-1 and TAFI. Lp(a) plasma levels significantly increased the maximal peak
      height of the clot lysis curve, indicating a change in clot structure. In this
      study Lp(a) is not related to the development of T2DM but may affect clot
      structure ex vivo without a prolongation of the clot lysis time. 

PMID- 24937706
TI  - Atomic layer-by-layer thermoelectric conversion in topological insulator
      bismuth/antimony tellurides.
AB  - Material design for direct heat-to-electricity conversion with substantial
      efficiency essentially requires cooperative control of electrical and thermal
      transport. Bismuth telluride (Bi2Te3) and antimony telluride (Sb2Te3), displaying
      the highest thermoelectric power at room temperature, are also known as
      topological insulators (TIs) whose electronic structures are modified by
      electronic confinements and strong spin-orbit interaction in a-few-monolayers
      thickness regime, thus possibly providing another degree of freedom for electron
      and phonon transport at surfaces. Here, we explore novel thermoelectric
      conversion in the atomic monolayer steps of a-few-layer topological insulating
      Bi2Te3 (n-type) and Sb2Te3 (p-type). Specifically, by scanning photoinduced
      thermoelectric current imaging at the monolayer steps, we show that efficient
      thermoelectric conversion is accomplished by optothermal motion of hot electrons
      (Bi2Te3) and holes (Sb2Te3) through 2D subbands and topologically protected
      surface states in a geometrically deterministic manner. Our discovery suggests
      that the thermoelectric conversion can be interiorly achieved at the atomic steps
      of a homogeneous medium by direct exploiting of quantum nature of TIs, thus
      providing a new design rule for the compact thermoelectric circuitry at the
      ultimate size limit. 

PMID- 24937708
TI  - Editorial.

PMID- 24937707
TI  - Deep brain and cortical stimulation for epilepsy.
AB  - BACKGROUND: Despite optimal medical treatment, including epilepsy surgery, many
      epilepsy patients have uncontrolled seizures. In the last decades, interest has
      grown in invasive intracranial neurostimulation as a treatment for these
      patients. Intracranial stimulation includes both deep brain stimulation (DBS)
      (stimulation through depth electrodes) and cortical stimulation (subdural
      electrodes). OBJECTIVES: To assess the efficacy, safety and tolerability of deep
      brain and cortical stimulation for refractory epilepsy based on randomized
      controlled trials. SEARCH METHODS: We searched PubMed (6 August 2013), the
      Cochrane Epilepsy Group Specialized Register (31 August 2013), Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7 of
      12) and reference lists of retrieved articles. We also contacted device
      manufacturers and other researchers in the field. No language restrictions were
      imposed. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing deep
      brain or cortical stimulation to sham stimulation, resective surgery or further
      treatment with antiepileptic drugs. DATA COLLECTION AND ANALYSIS: Four review
      authors independently selected trials for inclusion. Two review authors
      independently extracted the relevant data and assessed trial quality and overall
      quality of evidence. The outcomes investigated were seizure freedom, responder
      rate, percentage seizure frequency reduction, adverse events, neuropsychological
      outcome and quality of life. If additional data were needed, the study
      investigators were contacted. Results were analysed and reported separately for
      different intracranial targets for reasons of clinical heterogeneity. MAIN
      RESULTS: Ten RCTs comparing one to three months of intracranial neurostimulation
      to sham stimulation were identified. One trial was on anterior thalamic DBS (n =
      109; 109 treatment periods); two trials on centromedian thalamic DBS (n = 20; 40
      treatment periods), but only one of the trials (n = 7; 14 treatment periods)
      reported sufficient information for inclusion in the quantitative meta-analysis;
      three trials on cerebellar stimulation (n = 22; 39 treatment periods); three
      trials on hippocampal DBS (n = 15; 21 treatment periods); and one trial on
      responsive ictal onset zone stimulation (n = 191; 191 treatment periods).
      Evidence of selective reporting was present in four trials and the possibility of
      a carryover effect complicating interpretation of the results could not be
      excluded in 4 cross-over trials without any washout period. Moderate-quality
      evidence could not demonstrate statistically or clinically significant changes in
      the proportion of patients who were seizure-free or experienced a 50% or greater
      reduction in seizure frequency (primary outcome measures) after 1 to 3 months of
      anterior thalamic DBS in (multi)focal epilepsy, responsive ictal onset zone
      stimulation in (multi)focal epilepsy patients and hippocampal DBS in (medial)
      temporal lobe epilepsy. However, a statistically significant reduction in seizure
      frequency was found for anterior thalamic DBS (-17.4% compared to sham
      stimulation; 95% confidence interval (CI) -32.1 to -1.0; high-quality evidence),
      responsive ictal onset zone stimulation (-24.9%; 95% CI -40.1 to 6.0; high
      quality evidence) ) and hippocampal DBS (-28.1%; 95% CI -34.1 to -22.2; moderate
      quality evidence). Both anterior thalamic DBS and responsive ictal onset zone
      stimulation do not have a clinically meaningful impact on quality life after
      three months of stimulation (high-quality evidence). Electrode implantation
      resulted in asymptomatic intracranial haemorrhage in 3% to 4% of the patients
      included in the two largest trials and 5% to 13% had soft tissue infections; no
      patient reported permanent symptomatic sequelae. Anterior thalamic DBS was
      associated with fewer epilepsy-associated injuries (7.4 versus 25.5%; P = 0.01)
      but higher rates of self-reported depression (14.8 versus 1.8%; P = 0.02) and
      subjective memory impairment (13.8 versus 1.8%; P = 0.03); there were no
      significant differences in formal neuropsychological testing results between the
      groups. Responsive ictal-onset zone stimulation was well tolerated with few side
      effects but SUDEP rate should be closely monitored in the future (4 per 340 [=
      11.8 per 1000] patient-years; literature: 2.2-10 per 1000 patient-years). The
      limited number of patients preclude firm statements on safety and tolerability of
      hippocampal DBS. With regards to centromedian thalamic DBS and cerebellar
      stimulation, no statistically significant effects could be demonstrated but
      evidence is of only low to very low quality. AUTHORS' CONCLUSIONS: Only short
      term RCTs on intracranial neurostimulation for epilepsy are available. Compared
      to sham stimulation, one to three months of anterior thalamic DBS ((multi)focal
      epilepsy), responsive ictal onset zone stimulation ((multi)focal epilepsy) and
      hippocampal DBS (temporal lobe epilepsy) moderately reduce seizure frequency in
      refractory epilepsy patients. Anterior thalamic DBS is associated with higher
      rates of self-reported depression and subjective memory impairment. SUDEP rates
      require careful monitoring in patients undergoing responsive ictal onset zone
      stimulation. There is insufficient evidence to make firm conclusive statements on
      the efficacy and safety of hippocampal DBS, centromedian thalamic DBS and
      cerebellar stimulation. There is a need for more, large and well-designed RCTs to
      validate and optimize the efficacy and safety of invasive intracranial
      neurostimulation treatments.

PMID- 24937709
TI  - Aripiprazole: 6-month outcomes in a retrospective naturalistic study.
AB  - Aim. The efficacy of aripiprazole has been demonstrated in randomised controlled
      trials, but due to inclusion and exclusion criteria, these may not be
      representative of clinical practice. The aim of this naturalistic study was to
      investigate patients from an acute mental health trust who received aripiprazole,
      using treatment discontinuation as a primary outcome measure. Method. All
      patients with schizophrenia or schizoaffective disorder who had received
      aripiprazole were identified from pharmacy records, and data collected by
      retrospective case note review. Results. Seventy subjects were included in the
      study. A total of 28 (40%, n=70) patients remained on aripiprazole monotherapy at
      6 months. The most common reason for discontinuation was lack of effect, seen in
      29 patients; only 12 patients discontinued due to adverse effects. Thirty-five
      percent of the subjects had previously been treated with clozapine, although this
      did not appear to influence outcome. Conclusion. Despite limitations of the
      naturalistic methodology used in this study, it appears that aripiprazole is
      relatively well tolerated, and effective in clinical practice. The 40%
      continuation rate seen with aripiprazole is comparable to that seen with
      risperidone, quetiapine, and perphenazine in the CATIE study at 6 months. 

PMID- 24937705
TI  - Cultivable bacterial microbiota of northern bobwhite (Colinus virginianus): a new
      reservoir of antimicrobial resistance?
AB  - The northern bobwhite (Colinus virginianus) is an ecologically and economically
      important avian species. At the present time, little is known about the microbial
      communities associated with these birds. As the first step to create a quail
      microbiology knowledge base, the current study conducted an inventory of
      cultivable quail tracheal, crop, cecal, and cloacal microbiota and associated
      antimicrobial resistance using a combined bacteriology and DNA sequencing
      approach. A total of 414 morphologically unique bacterial colonies were selected
      from nonselective aerobic and anaerobic cultures, as well as selective and
      enrichment cultures. Analysis of the first 500-bp 16S rRNA gene sequences in
      conjunction with biochemical identifications revealed 190 non-redundant species
      level taxonomic units, representing 160 known bacterial species and 30 novel
      species. The bacterial species were classified into 4 phyla, 14 orders, 37
      families, and 59 or more genera. Firmicutes was the most commonly encountered
      phylum (57%) followed by Actinobacteria (24%), Proteobacteria (17%) and
      Bacteroidetes (0.02%). Extensive diversity in the species composition of quail
      microbiota was observed among individual birds and anatomical locations. Quail
      microbiota harbored several opportunistic pathogens, such as E. coli and Ps.
      aeruginosa, as well as human commensal organisms, including Neisseria species.
      Phenotypic characterization of selected bacterial species demonstrated a high
      prevalence of resistance to the following classes of antimicrobials: phenicol,
      macrolide, lincosamide, quinolone, and sulphate. Data from the current
      investigation warrant further investigation on the source, transmission,
      pathology, and control of antimicrobial resistance in wild quail populations. 

PMID- 24937710
TI  - Dynamics of inpatient child psychiatric care in the timeframe 1995-2005 (Vilnius
      University Child Developmental Centre).
AB  - Objective. The goals of this study were to analyse the formation of a
      multidisciplinary team, the variation of patient types and diagnoses in the Child
      Developmental Centre as well as the evolution of therapeutic interventions and
      trends of psychopharmacology in the timeframe 1995-2005. Methods. Analysis of
      medical documentation on personnel resources as well as general information about
      patients and applied therapeutic interventions was made. Results. The study
      results showed that the number of nurses and caretakers was gradually increasing
      and services became more adequate with inclusion of social workers, speech
      therapists and teachers. Analysis showed an increase in the following disorders:
      mood, hyperkinetic, mixed disorders of conduct and emotions, those with onset
      specific to childhood. The total number of children receiving pharmacological
      treatment increased. Conclusions. Delivery of adequate inpatient child
      psychiatric service is strongly dependent on administrative support, presence of
      qualified personnel, and adequate financial funding. There was a significant
      increase in the number of certain diagnoses and applied psychopharmacological
      treatment over the years studied that reflects international trends for
      treatment, prevalence and comorbidity of psychopathology in children. In view of
      child needs, establishment of age-specific inpatient units and development of
      special treatment programs are essential. 

PMID- 24937711
TI  - Quality of life and clinical characteristics of patients with generalized and
      performance-focused social anxiety disorder: An Italian study.
AB  - Introduction. The aim of this study is to investigate quality of life (QoL) and
      clinical characteristics of generalized (GSAD) and performance-focused social
      anxiety disorder (PFSAD). Method. Our sample includes 41 outpatients with social
      anxiety disorder and 100 control subjects. QoL was assessed using the Quality of
      Life and Enjoyment questionnaire. Assessments included the MINI Neuropsychiatric
      Interview, the Symptom Checklist, the Work and Social Adjustment Scale and the
      Clinical Global Impression Scale (CGI). Using the Liebowitz social anxiety scale,
      patients were divided into GSAD and PFSAD. Results. QoL of subjects with GSAD was
      lower than in controls in most areas, while only the areas of physical health and
      leisure time were impaired in patients with PFSAD. Patients with GSAD were more
      likely to be depressed, to meet criteria for substance abuse, to have higher
      severity scores on the CGI and the SCL-90 compared to PFSAD. Conclusions. GSAD is
      associated with widespread worsening of QoL, while patients with PFSAD had a
      poorer QoL than controls only in the areas of physical health and leisure time. 

PMID- 24937712
TI  - An open multicentre pilot study examining the safety, efficacy and tolerability
      of fast titrated (800 mg/day by day 4) quetiapine in the treatment of
      schizophrenia/schizoaffective disorder.
AB  - Objective. Rapid dose escalation of quetiapine could offer prompt and effective
      therapy to patients requiring hospitalization for schizophrenia or
      schizoaffective disorder. This study evaluated the safety, tolerability, and
      efficacy of a rapid dose escalation of quetiapine to 800 mg/day over 4 days in
      patients with severe psychotic symptoms diagnosed as schizophrenia or
      schizoaffective disorder. Methods. In this open-label, multicenter, pilot study,
      14 patients aged 18 years or older, requiring hospitalization for schizophrenia
      or schizoaffective disorder, received quetiapine orally twice daily for 14 days.
      Quetiapine was administered according to the schedule: 200, 400, 600, and 800
      mg/day on the first four treatment days, followed by flexible dosing within the
      range 400-800 mg/day during the next 10 days. The primary endpoint was to
      evaluate the safety and tolerability of a fast titration of quetiapine (200, 400,
      600, 800 mg/day on the first four treatment days). Effectiveness of a fast
      titration of quetiapine was the secondary objective of this investigation.
      Efficacy assessments in the intent-to-treat (ITT) population included changes in
      the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global
      Impression Severity of Illness (CGI-S) scores from Day 1 (baseline) to Day 14.
      Results. In 4 days 14 patients were titrated up to a dose of 800 mg/day. Ten
      patients were diagnosed with schizophrenia, one subject was suffering from
      schizoaffective disorder of the depressive type and three patients were diagnosed
      with schizoaffective disorder of the bipolar type. Eleven patients (79%)
      completed the study. Two patients discontinued the trial because of non
      compliance and one patient because of a prolonged QTcB interval. Overall, 29 AEs
      were reported during this trial, all were considered mild or moderate in
      severity. During the first 7 days of the trial, 25 AEs were reported in 11
      patients. The majority of AEs were considered as possibly related to the study
      medication. No deaths or serious adverse events were reported. Physical
      examination at the last trial visit revealed no clinically relevant changes
      versus baseline and there were no consistent changes over time in vital signs.
      The BARS and SAS scores indicated an improvement of EPS during the study. After 4
      days of fast titration, the mean total PANSS score decreased from 92.8 at
      baseline to a value of 87.4, there was a further decrease to 78.2 at endpoint.
      This corresponds to a statistically significant decrease by 14.6 versus baseline
      (P<0.01). After 4 days of fast titration, the mean CGI-S score was improved from
      4.7 at baseline to a value of 4.3 and improved further to 3.8 at endpoint,
      corresponding to a statistically significant decrease of 0.9 points versus
      baseline (P<0.01). Conclusion. In this study, fast titration of quetiapine to 800
      mg/day over 4 days was generally well tolerated and effective in reducing
      psychotic symptoms in patients requiring hospitalization for
      schizophrenia/schizoaffective disorder. 

PMID- 24937713
TI  - Early maladaptive schemas activated in patients with obsessive compulsive
      disorder: A cross-sectional study.
AB  - Aim. The aim of the present article is to investigate the activation patterns of
      early maladaptive schemas (EMSs) in patients with obsessive-compulsive disorder
      (OCD). Method. During the time between 1 January 2006 and 1 April 2006, 45
      consecutive patients from an outpatient facility of a general hospital and 45 age
      and gender-matched healthy control subjects from the hospital staff were
      included in the study. They were administered the Structured Clinical Interview
      for Diagnosis of DSM-IV Mental Disorders (SCID-1), the Structured Clinical
      Interview for DSM-III-R Personality Disorders (SCID-2), the Young Schema
      Questionnaire-Short Form (YSQ-SF), the Young Parenting Inventory (YPI) and the
      Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The results were assessed using
      GraphPad Prisma V.3 statistical program. Results. The YSQ total score of the OCD
      group was significantly higher than the control group (t=3.62, P<0.0001). The
      average scores of the patients with OCD on certain schemas were significantly
      higher than the average scores of the control group, although the others did not
      make any difference between the OCD and control groups. Conclusion. The study
      demonstrates that, in the patients with OCD, most of the early maladaptive
      schemas including social isolation, vulnerability and pessimism, are prominently
      activated. 

PMID- 24937714
TI  - Anxiety and depression and their influence on the quality of life after total hip
      replacement: preliminary report.
AB  - Objective. The study investigated health-related quality of life in relation to
      mental status (anxiety and depression) and demographic factors in patients before
      and after total hip replacement due to osteoarthrosis. Methods. The SF-36, HADS,
      socio-demographic data questionnaire was delivered to a group of 184 subjects
      (108 females, 76 males) at the mean age at the time of surgery of 59 years.
      Questionnaires were delivered to the subjects 2 weeks before the surgery and 6
      months after the operation (by mail). Results. Patients after hip replacement
      showed significant improvement in health-related quality of life in most domains
      of SF-36 score and summary scale of PCS (Physical Component Summary Scale) and
      MCS (Mental Component Summary Scale). They also showed improvement in mental
      status. Elderly patients were more likely to show worse score in MCS and PCS
      before and after surgery. BMI (body mass index) was correlated only with
      preoperative PCS. Mental status was associated with postoperative PCS and MCS.
      Patients who were satisfied with the results of the surgery showed higher PCS and
      MCS score. Conclusion. Hip replacement surgery brings significant improvement to
      the quality of life. Age and mental status of those patients influence markedly
      their postoperative performance. 

PMID- 24937715
TI  - The management of depression: An international naturalistic survey.
AB  - Objective. To investigate the management of major depression by primary care
      physicians (GP) and psychiatrists (PSY) in a naturalistic setting. Methods. GP
      and PSY from six countries replied to questions on the basis of the records of
      patients under treatment for depression. Results. Patients seen by GP and PSY
      were similar. Approximately 60% of patients had been treated for less than a year
      and about 20% for over 2 years. Continuous depressed mood and loss of interest or
      pleasure were present in about 75% of patients at diagnosis. Close to 60% of
      patients were treated with SSRIs and 15% with SNRIs. Most patients were also
      prescribed an anxiolytic, hypnotic or sedative. Although this was more common in
      patients with associated anxiety, 60% of patients with no anxiety at diagnosis
      were also prescribed anxiolytics by PSY (30% by GP). Most anxiolytic
      prescriptions were maintained throughout the depressive episode. Although the
      number of patients achieving full remission was only about 15%, changes in
      antidepressant medication during the depressive episode were rare. Conclusion.
      This naturalistic survey shows that in everyday practice in a number of countries
      adherence to guidelines for the treatment of depression is poor for both GP and
      PSY. 

PMID- 24937716
TI  - Generalized anxiety disorder and the circadian rhythm of blood pressure in
      patients with hypertension.
AB  - Objective. To investigate the impact of generalized anxiety disorder (GAD) on the
      circadian rhythm of blood pressure in patients with hypertension. Methods. The 24
      h ambulatory blood pressure was compared between patients with hypertension and
      GAD, and patients with hypertension only. Results. The mean day- and night-time
      systolic (SBP, 156.6+/-11.0 and 149.6+/-12.4 mmHg, respectively) blood pressure
      in patients with GAD was greater than in the no-GAD group (143.2+/-15.0 and
      126.0+/-10.8 mmHg, respectively, P<0.01). The mean day- and night-time diastolic
      blood pressure (DBP, 101.5+/-10.1 and 96.9+/-17.6 mmHg, respectively) in the GAD
      group was also greater than in the no-GAD group (94.1+/-10.9 and 77.4+/-10.2
      mmHg, respectively, P<0.01). SBP and DBP dipping was found in 87.5 and 80.1% of
      the hypertension only patients, as compared with 16.6 and 21.4% respectively, of
      the hypertension and GAD patients (P<0.01). Conclusions. The presence of GAD is
      associated with a higher level of blood pressure in hypertensive patients. GAD is
      also associated with a diminished circadian rhythm of blood pressure. The
      clinical significance of the reduced blood pressure dipping at night requires
      further investigation. 

PMID- 24937717
TI  - Catatonia is frequent in black immigrants admitted to Psychiatry in Canada.
AB  - Objective. To assess the prevalence of catatonia in a sample of patients of
      African ancestry admitted to Psychiatry in Canada. Methods. Retrospective chart
      review of 20 consecutive black francophone inpatients assessed by the same
      psychiatrist. Results. The sample consisted of 12 men and eight women aged 17-59
      years. Catatonic symptoms were prominent in 30% of this small sample (n=6), more
      frequent than the 9% reported in a Canadian general psychiatry population of 140
      inpatients (P=0.0126). Conclusions. This finding is limited by the small sample
      size and the provenance from troubled countries for most of the patients. It is
      consistent with earlier reports of a higher prevalence of catatonia in nonwhite
      subjects and among immigrants coming from developing countries, and stresses the
      importance of systematically assessing catatonia in clinical settings. Further
      research is warranted to distinguish between the effects of ethnic origin and
      immigrant status and to determine if the increased prevalence of catatonia is
      related to neurobiological causes such as maternal gestational infections or to
      socio-cultural factors. 

PMID- 24937718
TI  - Metabolic effects of olanzapine and risperidone in patients with psychotic
      disorders.
AB  - Objectives. Atypical anti-psychotic drugs are new medications proposed for
      treating psychotic disorders. This study was designed to investigate the
      metabolic (blood sugar and lipid) and adverse effects of olanzapine and
      risperidone in psychotic patients. Methods. In this randomized double-blinded
      clinical trial, psychotic patients were randomly categorized to be treated with
      olanzapine or risperidone. All the subjects were initially assessed for blood
      sugar and lipids, and, where normal, were included. Blood sugar and lipids
      measurements were performed for all subjects at 1 week and after 3 months the
      initiation of therapy, and they were assessed for other complications as well.
      The data were subsequently analyzed using SPSS software. Results. The levels of
      blood sugar, cholesterol, and triglyceride rose significantly after 1 week and 3
      months of therapy (P<0.001); the difference in rise of cholesterol and
      triglyceride in the olanzapine and the risperidone groups was significant
      (P<0.001), whereas the difference in blood sugar rise was not significant
      (P>0.05). Other complications including restlessness, impotence, weight gain,
      edema and drowsiness were significantly different between the two groups.
      Conclusion. According to the study findings, we recommend more caution in the
      application of atypical antipsychotic drugs in high risk patients. 

PMID- 24937719
TI  - A double-blind comparative study of clinical efficacy of verapamil versus lithium
      in acute mania.
AB  - Objectives. The importance of intracellular calcium ions to processes that may be
      involved in mania and the calcium antagonist action of mood stabilizers suggest a
      role of verapamil in the treatment of mania. This study was undertaken to compare
      the clinical efficacy and tolerability of verapamil versus lithium in manic
      patients. Methods. Patients with acute mania were randomized to receive lithium
      (N =25) or verapamil (N =25) in a 4-week double-blind comparative study. Both
      groups were homogeneous with regard to demographic and disease variables. The
      primary efficacy measures were the mean change from the baseline to the last
      assessment in BRMS (Bech-Raefelson Mania Rating Scale) and YMRS (Young-Mania
      Rating scale) total score. The rating scales were administered to the patients on
      day 1, 3, 5, 7, 11, 13, 17, 21, 28 of the study. Attendant's assessment of relief
      and adverse events were recorded during the study. Results. Both treatment groups
      showed significant decrease in mean BRMS and YMRS score assessed at different
      points of time. The study showed an equal efficacy of verapamil compared with
      lithium in the treatment of mania. The findings were supported by good
      tolerability of verapamil treatment. Conclusion. This study found equal benefit
      of verapamil over lithium in treating acute mania. 

PMID- 24937720
TI  - Buccal midazolam for agitation on psychiatric intensive care wards.
AB  - Midazolam is a benzodiazepine known to be effective as a treatment for status
      epilepticus and for rapid tranquillisation. Buccal midazolam has recently become
      available in the UK. We introduced it as a treatment option for rapid
      tranquillisation on our intensive care wards. Buccal midazolam was found to be
      effective and well tolerated. Target levels of sedation were achieved in nearly
      70% of subjects within half an hour. Activity was evident within 15 minutes. Over
      sedation occurred in only one patient at one time point. There were no cases of
      respiratory depression. Buccal midazolam deserves further investigation as a non
      invasive treatment option in rapid tranquillisation. 

PMID- 24937721
TI  - The prediction of healthcare utilization by three self-report measures for
      borderline personality.
AB  - Objective. In this study, we explored the ability of three self-report measures
      for borderline personality disorder (BPD) to predict psychiatric and medical
      (i.e. non-psychiatric) healthcare utilization. Methods. Using a sample of
      convenience and survey methodology, we asked participants (N=120) to complete the
      borderline personality scale of the Personality Diagnostic Questionnaire-4 (PDQ
      4), the Self-Harm Inventory (SHI), the McLean Screening Inventory for Borderline
      Personality Disorder (MSI-BPD), and several variables relating to psychiatric and
      medical healthcare utilization. Results. The SHI demonstrated the greatest number
      of correlations with healthcare utilization, particularly with regard to
      psychiatric care. Conclusions. The SHI provides several functions for clinicians
      including the identification of self-harm behaviors, confirmation of the
      diagnosis BPD, and prediction of psychiatric healthcare utilization. 

PMID- 24937724
TI  - Commentary on "Maternal mortality in the Mississippi Delta region".

PMID- 24937723
TI  - Maternal mortality in the Mississippi Delta region.
AB  - OBJECTIVE: To compare the maternal mortality rate (MMR) in the Mississippi Delta
      region of the United States with that of the non-Delta region states. METHODS:
      Analyzed data come from national birth certificate and death certificate data for
      1999-2007. Data were aggregated for analysis by region, counties of the Delta
      Regional Authority, non-Delta regions of the eight Delta states, and the 42 non
      Delta states. The MMR was calculated using birth data as the denominator and
      maternal mortality data as the numerator. RESULTS: During the 9 years of the
      study, there were more than 36 million births in the United States and 5002
      reported maternal deaths. The national MMR was 13.5/100,000 (95% confidence
      interval [CI] 13.1-13.9/100,000). The MMR reported in the non-Delta states was
      13.6/100,000 (95% CI 13.2-14.0/100,000); in the non-Delta counties of the Delta
      states, the MMR was 13.1/100,000 (95% CI 12.1-14.0/100,000); and the MMR was
      18.5/100,000 (95% CI 16.1-20.9/100,000) in Delta counties. The odds of maternal
      death in Delta counties is 1.39 times (95% CI 1.22-1.59) higher compared with non
      Delta counties or non-Delta states. There was no statistically significant
      difference between the MMR in non-Delta states and the MMR in non-Delta counties
      of Delta states. After controlling for maternal race/ethnicity, age, marital
      status, and education in a multivariable model, the MMR in the Delta counties
      compared with non-Delta counties and non-Delta states remains significantly
      increased (odds ratio 1.16, 95% CI 1.01-1.32). CONCLUSIONS: Overall, maternal
      mortality is significantly greater in the Delta region of the United States
      compared with the non-Delta portion. After controlling for maternal
      race/ethnicity, age, marital status, and education, the odds of maternal death
      remains 16% higher in the Delta region of the United States compared with the non
      Delta United States.

PMID- 24937725
TI  - Geographic variations of racial/ethnic disparities in cervical cancer mortality
      in Texas.
AB  - OBJECTIVES: To examine how racial/ethnic disparities of cervical cancer mortality
      vary geographically and to identify factors contributing to the variation.
      METHODS: Using the population-weighted risk difference, the authors investigated
      geographic patterns of racial/ethnic disparities in cervical cancer mortality in
      Texas based on data from 1995 to 2008 georeferenced at the census tract level. In
      addition, we considered the impact of seven factors--stage at diagnosis, spatial
      access to health care, and five factors that were created from available
      demographic data: socioeconomic status (SES), the sociodemographic factor, the
      percentage of African Americans, the health insurance factor, and the behavioral
      factor--on racial/ethnic disparities in the analysis using multivariate logistic
      regression. RESULTS: SES, the sociodemographic factor, the percentage of African
      Americans, and racial/ethnic disparities in late-stage diagnosis in a census
      tract were independent predictors of a census tract's displaying significant
      racial/ethnic disparities in cervical cancer mortality. Compared with a census
      tract with the highest SES, a census tract with the lowest SES was more likely to
      have higher mortality rates in African Americans (odds ratio 4.19, confidence
      interval 2.18-8.07) or Hispanics (odds ratio 8.15, confidence interval 5.27
      12.61) than non-Hispanic whites after adjusting for covariates. Health insurance
      expenditures also influenced racial/ethnic disparities in mortality, although
      this effect was attenuated after adjusting for covariates. Neither our calculated
      behavioral factor nor spatial analysis of access to health care explained
      racial/ethnic gaps in mortality. CONCLUSIONS: Findings from this study could
      allow cervical cancer intervention programs to more clearly identify areas that
      would reduce disparities in cervical cancer outcomes.

PMID- 24937726
TI  - Endoscopic surveillance for gastric ulcers.
AB  - OBJECTIVE: Gastric ulcers (GUs) can be caused by a malignancy, and endoscopists
      are challenged with the question of how to rule out underlying malignancy.
      Although routine endoscopic surveillance is not advised, it is still overused.
      The purpose of this study was to explore the practice in our tertiary referral
      center during the last 3 years. METHODS: We retrospectively reviewed all
      inpatient and outpatient esophagogastroduodenoscopies (EGDs) that were performed
      between November 2009 and November 2012 for GUs. Patients with GUs who normally
      would not undergo biopsy, such as patients who present with bleeding or had
      stigmata of high-risk bleeding, were excluded. RESULTS: A total of 165 patients
      were diagnosed between November 2009 and November 2012 as having GUs on EGD.
      Fifty-two patients were excluded because they presented with bleeding or had GUs
      that had stigmata of high-risk bleeding. We reviewed the charts of 113 patients
      and endoscopic surveillance was recommended for 96 (85%). Of those 96 patients,
      72 (64%) underwent repeat EGD. In those 72 patients, GU was still present in 9
      patients and was completely healed or healing in 63 patients. Only 25 (22%) GUs
      were biopsied at initial EGD, 23 of which were benign and 2 were adenocarcinomas.
      No additional malignancy was found on surveillance EGD. CONCLUSIONS: EGD
      surveillance for GUs is a common practice, although the guidelines discourage
      such a practice. Our rate of endoscopic surveillance was significantly higher
      than reported previously (64% vs 25%). In our experience, such a high rate of
      surveillance did not reveal any additional gastric malignancy. Alternatively, the
      rate of biopsy of GUs at initial EGD is low (22%), which also reflects
      endoscopists' preference for endoscopic surveillance.

PMID- 24937727
TI  - Prescriptions for a toxic combination: use of methotrexate plus trimethoprim
      sulfamethoxazole in the United States.
AB  - OBJECTIVES: To determine the frequency of using the potentially toxic combination
      of methotrexate and trimethoprim-sulfamethoxazole (TMP-SMX) in outpatient
      practice in the United States. METHODS: Data from the National Ambulatory Medical
      Care Survey for 1993-2010 were used to assess the frequency of using methotrexate
      with TMP-SMX and associated physician specialties and diagnoses. RESULTS: TMP-SMX
      was coprescribed in 22,000 methotrexate visits per year (1.0% of methotrexate
      visits). Pediatricians prescribed the combination most frequently, and the most
      common diagnosis was acute lymphoblastic leukemia. There was no significant
      change over time in coprescription of TMP-SMX with methotrexate (P = 0.4).
      CONCLUSIONS: Low-dose TMP-SMX with methotrexate chemotherapy appears to be
      standard for patients with acute lymphoblastic leukemia; however, other uses
      appear questionable, and clinicians should be cognizant of the risk for fatal
      interactions, especially when medications are prescribed by multiple providers.

PMID- 24937728
TI  - Analysis of fall injuries by body mass index.
AB  - OBJECTIVE: To examine the association of body mass index (BMI) and fall injuries.
      METHODS: Data were derived from the 2010 Behavioral Risk Factor Surveillance
      System and included subjects aged 45 years and older from Texas. The outcome was
      self-reported falls that resulted in injury to the respondents. Analysis of fall
      injuries by BMI was conducted and standard errors, 95% confidence intervals
      (CIs), and coefficients of variation were reported. Complex sample multivariate
      Poisson regression was used to examine the association of BMI and fall injuries.
      RESULTS: A total of 18,077 subjects were surveyed in 2010, and 13,235 subjects
      were aged 45 years old and older. The mean BMI was higher (29.94 vs 28.32
      kg/m(2)) among those who reported fall injuries compared with those who did not.
      The fall injuries reported by obese respondents (relative risk [RR] 1.67) were
      found to be significantly (P = 0.031) higher compared with normal-weight
      respondents in the multivariate regression. Other risk factors that had
      significant association with fall injuries (when adjusted for BMI) were activity
      limitations (RR 5.00, 95% CI 3.36-7.46) compared with no limitations, and not
      having formal employment (homemaker: RR 2.68, 95% CI 1.33-5.37; unable to work:
      RR 5.01, 95% CI 1.87-13.29; out of work and students: RR 3.21, 95% CI 1.41-7.29)
      compared with the employed population. CONCLUSIONS: There is a significant
      association between obesity and fall injuries in adults aged 45 years old and
      older in Texas. Interventions in fall prevention, although generally targeted at
      present to older adults, also should take into account the weight status of the
      subjects.

PMID- 24937729
TI  - Physicians caring for physicians: the perspective of the primary care physician.
AB  - OBJECTIVES: How physicians provide longitudinal primary care to physician
      patients (ie, physicians as patients) has not been well studied. The potential
      challenges of providing care to physician-patients include maintaining
      professional boundaries and adhering to practice guidelines. The objective was to
      explore the differences in identifying how physicians perceive caring for
      physicians-patients in the longitudinal setting versus caring for other patients
      in the general population. METHODS: The study consisted of focus groups, followed
      by quantitative survey. Participants were primary care physicians (internal
      medicine and family medicine) at an academic multispecialty group practice.
      Thematic analysis of focus groups informed the development of the survey.
      RESULTS: In focus groups, participants identified several benefits, challenges,
      and differences in caring for physician-patients versus the general population.
      When these findings were explored further by quantitative survey, participants
      noted differences in care regarding chart documentation protocols, communication
      of results, and accommodation of schedules. They agreed that there were benefits
      to providing care to physician-patients, such as believing their work was valued
      and discussing complex issues with greater ease. There also were challenges,
      including anxiety or self-doubt. Participants also agreed on the following
      strategies when caring for this population: make recommendations based on
      evidence-based medicine, follow routine assessment and examination protocols,
      follow routine scheduling and communication protocols, recommend the same follow
      up visit schedule, and define boundaries of the relationship. CONCLUSIONS:
      Physicians perceive caring for physician-patients as different and rewarding,
      although some find that it provokes anxiety. Many are willing to make concessions
      regarding scheduling and testing. With increasing experience, the anxiety
      decreased as did the need to follow protocols and maintain boundaries. Further
      investigation is needed to determine the impact of physician experience and
      training on the quality of care for physician-patients.

PMID- 24937730
TI  - Commentary on "Physicians caring for physicians: the perspective of the primary
      care physician".

PMID- 24937732
TI  - Commentary on "Feeding after percutaneous endoscopic gastrostomy: experience of
      early versus delayed feeding".

PMID- 24937731
TI  - Feeding after percutaneous endoscopic gastrostomy: experience of early versus
      delayed feeding.
AB  - BACKGROUND: Multiple studies have demonstrated that feeding <=4 hours after
      placement of a percutaneous endoscopic gastrostomy (PEG) tube is a reasonable
      option. Many physicians, however, continue to delay feedings until the next day
      or 24 hours; therefore, we evaluated the safety and effect of early feeding (<=4
      hours) after PEG placement in our tertiary care center. METHODS: A retrospective
      study of 444 patients who underwent PEG between June 2006 and December 2011 was
      performed. Early feeding was defined as feeding <=4 hours and delayed feeding was
      defined as feeding >4 hours. Statistical analysis was performed using the Fisher
      exact test and the Student t test. RESULTS: A total of 444 patients underwent PEG
      between June 2006 and December 2011. A majority of PEGs were performed on
      inpatients by gastroenterologists. The mean time of feeding after PEG was 3.2 +/-
      0.9 hours for the early group (n = 197) and 17.0 +/- 10.0 hours for the delayed
      group (n = 247). No statistically significant differences were noted between the
      early (<=4 hours) feedings versus the delayed (>4 hours) feedings for overall
      morality within 30 days (P = 0.72) and overall complications (P = 1.00).
      Furthermore, no statistically significant differences were noted between early
      versus delayed feeding for 24-hour mortality (P = 1.00), 24- to 72-hour mortality
      (P = 0.20), and 3-30 days mortality (P = 0.86). For each complication, there were
      no statistically significant differences noted between the two groups for wound
      infection (P = 0.52), melena (P = 0.26), vomiting (P = 0.42), leakage (P = 0.41),
      stomatitis (P = 0.13), aspiration pneumonia (P =1.00), and other complications (P
      = 0.47). CONCLUSIONS: Feeding <=4 hours after PEG appears to be as safe as
      delayed feeding. Based on this study and the literature, strong consideration for
      the majority of patients should be undertaken to begin feeding within 4 hours
      after PEG.

PMID- 24937733
TI  - Using motivational interviewing for smoking cessation in primary care.
AB  - OBJECTIVES: To compare the effects of resident physician motivational
      interviewing (MI), resident physician MI plus registered nurse (RN), and the
      standard of care counseling approach--ask, advise, assess, assist, and arrange
      follow-up (5 As)--on current smokers' behaviors (readiness to quit, cigarettes
      smoked per day, current smoking rates), self-efficacy to quit smoking, and
      nicotine dependence. METHODS: The study design was quasi-experimental
      pretest/posttest with a comparison group. Pencil/paper measures were completed in
      the clinic setting at baseline and via telephone approximately 1 and 2 months
      after the clinic visit. RESULTS: There were no differences among the three groups
      in the proportion of participants who quit smoking, and the stages of change did
      not differ among the groups or over time. There was a significant time effect and
      a decrease in the number of cigarettes smoked per day (F2,160 = 41.04, P <
      0.001). Significant group * time interactions were present for self-efficacy
      (F4,140 = 8.20, P < 0.001), nicotine dependence (F4,140 = 6.22, P < 0.001) and
      satisfaction with clinician (F4,160 = 3.81, P = 0.006). Post hoc analyses showed
      that participants in the MI groups smoked fewer cigarettes, had higher self
      efficacy, and had lower nicotine dependence scores. Only participants in the MD
      plus-RN follow-up group had significant positive changes in satisfaction scores.
      CONCLUSIONS: Resident physicians who use MI techniques have a tremendous effect
      on patients' smoking behaviors. When the resident physician and the RN worked
      together, participants achieved better outcomes.

PMID- 24937734
TI  - Patterns of Internet use by gastroenterologists in the management and education
      of patients with inflammatory bowel disease.
AB  - AIMS: To define the patterns of Internet use among physicians who treat
      inflammatory bowel disease (IBD) and physicians' perceptions of their patients'
      Internet use. METHODS: An online survey about physician and patient use of the
      Internet was created and e-mailed to gastroenterologists nationwide. Surveys were
      distributed and collected via an online database and a subsequent statistical
      analysis was performed. RESULTS: Of the 1000 e-mail invitations sent to
      practicing gastroenterologists in the United States, 223 participants (22.3%)
      completed the survey. A total of 183 (82.1%) physicians reported using an
      Internet-based reference to assist them in deriving management strategies for
      their patients with IBD, with the most commonly utilized resource being UpToDate
      followed by PubMed and the Crohn's and Colitis Foundation of America Web site.
      Although nearly 80% of gastroenterologists believed that using the Internet
      helped them facilitate clinical discussions, 183 participants (82.1%) believed
      that inaccurate information found online could sometimes result in increased
      clinic time because physicians must spend more time dispelling misleading
      information. CONCLUSIONS: Despite a study design biased toward selecting
      gastroenterologists who commonly used the Internet, we demonstrated that only 60%
      of the providers routinely refer their patients to the Internet. This underscores
      the fact that it is important to have a centralized "physician-certified" online
      resource to which physicians could readily refer their patients to navigate
      through various disease-specific resources without concern that their patients
      are receiving unreliable or misleading information.

PMID- 24937735
TI  - Acromioclavicular osteoarthritis: a common cause of shoulder pain.
AB  - Osteoarthritis of the acromioclavicular joint is a frequent cause of shoulder
      pain and can result in significant debilitation. It is the most common disorder
      of the acromioclavicular joint and may arise from a number of pathologic
      processes, including primary (degenerative), posttraumatic, inflammatory, and
      septic arthritis. Patients often present with nonspecific complaints of pain
      located in the neck, shoulder, and/or arm, further complicating the clinical
      picture. A thorough understanding of the pertinent anatomy, disease process,
      patient history, and physical examination is crucial to making the correct
      diagnosis and formulating a treatment plan. Initial nonoperative management is
      aimed at relieving pain and restoring function. Typical treatments include anti
      inflammatory medications, physical therapy, and injections. Patients who continue
      to exhibit symptoms after appropriate nonsurgical treatment may be candidates for
      operative resection of the distal clavicle through either open or arthroscopic
      techniques. 

PMID- 24937736
TI  - Tiotropium in the treatment of patients with asthma.
AB  - BACKGROUND: Asthma is a chronic disease with a significant disease burden, and
      many patients fail to achieve disease control despite recommended medical
      therapy. Recent evidence suggests that there may be benefits to the use of the
      long-acting anticholinergic agent tiotropium in patients with asthma. METHODS: We
      performed a systematic review of the literature to determine the role of
      tiotropium in management of adult patients with asthma. RESULTS: In six studies,
      1773 patients were randomized and 1057 received tiotropium as an intervention.
      The mean prebronchodilator forced expiratory volume in 1 second was 60.1%. All
      six studies reported a small but statistically significant improvement in
      spirometry when using tiotropium as compared with the control. Improvement was
      reported in patients with both moderate and severe asthma, patients uncontrolled
      on previous regimens, patients treated with low- to high-dose inhaled
      corticosteroids regimens, and patients treated with and without long-acting beta
      agonist therapy. Five studies evaluated clinical outcomes with tiotropium with
      variable success rates. Although a large randomized trial demonstrated a
      reduction in the frequency of severe asthma exacerbation with tiotropium, there
      is insufficient evidence to support the argument that tiotropium therapy leads to
      improvements in asthma symptom measures, asthma control days, asthma-related
      quality-of-life-scores, or rescue inhaler use. CONCLUSIONS: There is strong
      evidence supporting improvement in spirometry and asthma exacerbations with
      tiotropium in patients with moderate and severe asthma; therefore, tiotropium may
      be an effective intervention in patients with asthma.

PMID- 24937737
TI  - Commentary on "Tiotropium in the treatment of patients with asthma".

PMID- 24937741
TI  - High kinetic energy ion mobility spectrometer: quantitative analysis of gas
      mixtures with ion mobility spectrometry.
AB  - We present a high kinetic energy ion mobility spectrometer (HiKE-IMS) for
      quantitative gas analysis. Drift tube and reaction tube can be operated at
      reduced fields up to 110 Td. At such conditions the distribution of reactant ion
      water clusters is shifted toward smaller clusters. Due to the resulting presence
      of bare reactant ions (e.g., H3O(+)) and the kinetic control of the ionization
      process with decreasing reaction time, unlike conventional IMS, a quantitative
      detection with ppbv detection limits of low proton affine analytes even in humid
      gas mixtures containing high proton affine compounds is possible using a direct
      sample gas inlet. A significantly improved dynamic range compared to conventional
      IMS is achieved. An incremental change in reduced fields enables the observation
      of parameters like field dependent ion mobilites or analyte fragmentation. Also,
      the characteristic of the analyte signal with respect to the reduced reaction
      field gives insight into the ionization process of the analyte. Thus, HiKE-IMS
      enables substance identification by ion mobility and additional analytical
      information that are not observed with conventional IMS. The instrumental effort
      is similar to conventional desktop IMS with overall dimensions of the drift and
      reaction tube of 4 cm * 4 cm * 28.5 cm. However, the mobility resolution is
      limited and between 30 and 40. Because of the moisture independent ionization and
      the decrease in competing ion-molecule reactions, no preseparation or membrane
      inlet is necessary when the compounds of interest are distinguishable either by a
      significant difference in ion mobility or the additional analytical information. 

PMID- 24937740
TI  - Efficient and regiospecific syntheses of peptides with piperazic and
      dehydropiperazic acids via a multicomponent reaction.
AB  - Peptides containing N2-acyl piperazic or 1,6-dehydropiperazic acids can be formed
      efficiently via a novel multicomponent reaction of 1,4,5,6-tetrahydropyridazines,
      isocyanides, and carboxylic acids. Remarkably, the reaction's induced
      intramolecularity can enable the regiospecific formation of products with N2-acyl
      piperazic acid, which counters the intrinsic and troublesome propensity for
      piperazic acids to react at N1 in acylations. The utility of the methodology is
      demonstrated in the synthesis of the bicyclic core of the interleukin-1beta
      converting enzyme inhibitor, Pralnacasan. 

PMID- 24937739
TI  - Increased response to a 5-HT challenge after discontinuation of chronic serotonin
      uptake inhibition in the adult and adolescent rat brain.
AB  - Little is known about the effects of chronic fluoxetine on 5-HT transmission in
      the adolescent brain, even though it is acknowledged that the neuroplasticity of
      the brain during childhood and adolescence might influence the neurobiological
      mechanisms underlying treatment response. Also, possible ongoing effects on
      monoamine function following drug discontinuation are unidentified. We therefore
      examined the chronic effects of fluoxetine on extracellular 5-HT and dopamine
      concentrations in the medial prefrontal cortex and studied their responsiveness
      to an acute 5-HT challenge after a one-week washout period, both in adolescent
      and adult rats. Noradrenaline was measured in adult animals only. Fluoxetine
      increased 5-HT to 200-300% of control and DA and NA to 150% of control. Although
      there were no lasting effects of chronic fluoxetine on basal monoamine levels, we
      observed a clear potentiating effect of previous treatment on the fluoxetine
      induced increase in extracellular 5-HT and, to a lesser extent, extracellular DA.
      No differential effect was found for noradrenaline. Age-at-treatment did not
      influence these results. So, after cessation of chronic fluoxetine treatment 5-HT
      responsiveness remains heightened. This may be indicative of the continuing
      presence of 5-HT receptor desensitization, at least until one week after drug
      discontinuation in rats. No apparent age-at-treatment effects on extracellular
      monoamine concentrations in the medial prefrontal cortex were detected, but age
      related differences in 5-HT transmission further down-stream or in the recovery
      processes cannot be ruled out. 

PMID- 24937742
TI  - To ID or not to ID? Changes in classification rates of intellectual disability
      using DSM-5.
AB  - The Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5)
      diagnostic criteria for intellectual disability (ID) include a change to the
      definition of adaptive impairment. New criteria require impairment in one
      adaptive domain rather than two or more skill areas. The authors examined the
      diagnostic implications of using a popular adaptive skill inventory, the Adaptive
      Behavior Assessment System-Second Edition, with 884 clinically referred children
      (ages 6-16). One hundred sixty-six children met DSM-IV-TR criteria for ID;
      significantly fewer (n  =  151, p  =  .001) met ID criteria under DSM-5 (9%
      decrease). Implementation of DSM-5 criteria for ID may substantively change the
      rate of ID diagnosis. These findings highlight the need for a combination of
      psychometric assessment and clinical judgment when implementing the adaptive
      deficits component of the DSM-5 criteria for ID diagnosis.

PMID- 24937743
TI  - Facilitators and barriers to physical activity as perceived by older adults with
      intellectual disability.
AB  - Older people with intellectual disability (ID) are characterized by low physical
      activity (PA) levels. PA is important for reducing health risks and maintaining
      adequate fitness levels for performing activities of daily living. The aim of
      this study was to explore preferences of older adults with ID for specific
      physical activities, and to gain insight into facilitators and barriers to
      engaging into PA. Fourteen in-depth interviews and four focus groups were
      undertaken, with a total of 40 older adults with mild and moderate ID included in
      the analysis. NVivo software was used for analysing the transcribed verbatim
      interviews. In total, 30 codes for facilitators and barriers were identified.
      Themes concerning facilitators to PA were enjoyment, support from others, social
      contact and friendship, reward, familiarity, and routine of activities. Themes
      concerning barriers to PA were health and physiological factors, lack of self
      confidence, lack of skills, lack of support, transportation problems, costs, and
      lack of appropriate PA options and materials. The results of the present study
      suggest that older adults with ID may benefit from specific PA programs, adapted
      to their individual needs and limitations. Results can be used for developing
      feasible health promotion programs for older adults with ID.

PMID- 24937744
TI  - Hospitalizations of adults with intellectual disability in academic medical
      centers.
AB  - Individuals with intellectual disability (ID) represent a small but important
      group of hospitalized patients who often have complex health care needs.
      Individuals with ID experience high rates of hospitalization for ambulatory
      sensitive conditions and high rates of hospitalizations in general, even when in
      formal community care systems; however, no research was found on the common
      reasons for which this population is hospitalized. Academic medical centers often
      treat the most complex patients, and data from these centers can provide insight
      into the needs of patient populations with complex needs. The purpose of this
      study was to analyze descriptive data from the UHC (formerly known as the
      University Healthsystem Consortium; an alliance of 115 U.S. academic medical
      centers and 300 of their affiliated hospitals) regarding common reasons for
      hospitalization, need for intensive care, and common hospitalization outcome
      measures of length of stay and complications for adult (age >= 18) patients with
      ID. Findings indicate the need for specific attention to the needs of
      hospitalized patients with ID.

PMID- 24937746
TI  - What it's like to grow older: the aging perceptions of people with an
      intellectual disability in Ireland.
AB  - The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing
      is a national longitudinal study on the aging of people with an intellectual
      disability (ID) using a randomly selected sample of people with ID over the age
      of 40. In total, 367 people with an ID completed the aging perception self-report
      only section. Over 57% of people described their health as very good to excellent
      with no significant difference in health perceptions found for gender, level of
      ID, or living circumstance. Exploring people's perceptions utilizing PASW Text
      Analytics for Surveys 4.1 perceptions often supported negative views of the
      consequences of aging. These findings suggest challenging negative aging concepts
      is essential to promote positivity with associated improved health and wellbeing.

PMID- 24937745
TI  - U.S. emergency department admissions for nontraumatic dental conditions for
      individuals with intellectual and developmental disabilities.
AB  - The authors hypothesized that individuals with intellectual and developmental
      disabilities (IDDs) are more likely to have an emergency department (ED)
      admission for nontraumatic dental conditions (NTDCs). The authors analyzed 2009
      U.S. National Emergency Department Sample data and ran logistic regression models
      for children ages 3-17 years and adults age 18 years or older. The prevalence of
      NTDC-related ED admissions was 0.8% for children and 2.0% for adults. Children
      with IDDs were at increased odds of NTDC-related ED admission, but this
      difference was not statistically significant (odds ratio [OR]  =  1.06; 95%
      confidence interval [CI]  =  0.91, 1.23). Adults with IDDs had significantly
      lower odds of an ED admission for NTDCs (OR  =  0.49; 95% CI  =  0.44, 0.54).
      Children with IDDs are not at increased odds of NTDC-related ED admissions,
      whereas adults with IDDs are at significantly reduced odds.

PMID- 24937747
TI  - Intellectual and developmental disabilities in Kinshasa, Democratic Republic of
      the Congo: causality and implications for resilience and support.
AB  - This article reports results of a 7-month qualitative study on intellectual and
      related developmental disabilities in Kinshasa, Democratic Republic of the Congo,
      particularly as they relate to the causes and meaning of intellectual and
      developmental disabilities (IDD). This study raises important questions related
      to the understanding of resilience of persons affected by IDD and the nature and
      purpose of support they use or desire.

PMID- 24937751
TI  - Obestatin and Nt8U influence glycerolipid metabolism and PPAR gamma signaling in
      mice.
AB  - Obestatin, its N-terminal fragment and the N-terminal fragment analog Nt8U were
      previously shown to reduce food intake, gain in body weight and triglyceride
      levels in albino mice. To establish their mode of action, mRNA profiling of the
      epididymal adipose tissue of mice treated with these peptides were performed. The
      differential expressions were markedly indicative of their involvement in lipid
      metabolism. Obestatin showed a significant upregulation of the genes patatin-like
      phospholipase domain containing 3, diacylglycerol O-acyltransferase 2,
      monoglyceride lipase, aldo-keto reductase family 1, member 7 which are involved
      in glycerolipid metabolism. It also upregulated peroxisome proliferator-activated
      receptor gamma, retinoid X receptor gamma, cluster of differentiation 36,
      adiponectin, C1Q and collagen domain containing, angiopoietin-like 4, lipoprotein
      lipase, stearoyl-coenzyme A and desaturase 3 involved in the peroxisome
      proliferator-activated receptor signaling pathway. Nt8U upregulated genes
      implicated in the same two pathways but with lesser significance and also
      upregulated APOL2. The N-terminal fragment though differentially regulated a
      small subset of the genes differentially regulated by obestatin and Nt8U, no
      conclusive evidence was obtained as to assign a specific pathway for its mode of
      action. We hypothesize that reduced food intake brought about by obestatin and
      Nt8U triggers lipid catabolism. The free fatty acids and lysophosphatidic acid
      thus produced in turn activates peroxisome proliferator-activated receptor gamma
      and the genes involved in peroxisome proliferator-activated receptor signaling.
      All of them together lead to reduction in gain in bodyweight, stored fat and
      circulating lipids. These results also correlate well with the observed efficacy
      of the peptides. 

PMID- 24937750
TI  - Microtubules depolymerization caused by the CK1 inhibitor IC261 may be not
      mediated by CK1 blockage.
AB  - The ubiquitously expressed serine/threonine specific casein kinase 1 (CK1) family
      plays important roles in the regulation of various physiological processes. Small
      molecule inhibitors, such as the CK1delta/epsilon selectively inhibitor IC261,
      have been used to antagonize CK1 phosphorylation events in cells in many studies.
      Here we present data to show that, similarly to the microtubule destabilizing
      agent nocodazole, IC261 depolymerizes microtubules in interphase cells. IC261
      treatment of interphase cells affects the morphology of the TGN and Golgi
      apparatus as well as the localization of CK1delta, which co-localizes with COPI
      positive membranes. IC261-induced depolymerization of microtubules is rapid,
      reversible and can be antagonized by pre-treatment of cells with taxol. At lower
      concentrations of IC261, mitotic spindle microtubule dynamics are affected; this
      leads to cell cycle arrest and, depending on the cellular background, to
      apoptosis in a dose-dependent manner. In addition, FACS analysis revealed that
      IC261 could induce apoptosis independent of cell cycle arrest. In summary this
      study provides additional and valuable information about various IC261-induced
      effects that could be caused by microtubule depolymerization rather than by
      inhibition of CK1. Data from studies that have used IC261 as an inhibitor of CK1
      should be interpreted in light of these observations. 

PMID- 24937752
TI  - Architectural and functional similarities between trimeric ATP-gated P2X
      receptors and acid-sensing ion channels.
AB  - ATP-gated P2X receptors and acid-sensing ion channels are two distinct ligand
      gated ion channels that assemble into trimers. They are involved in many
      important physiological functions such as pain sensation and are recognized as
      important therapeutic targets. They have unrelated primary structures and respond
      to different ligands (ATP and protons) and are thus considered as two different
      ion channels. As a consequence, comparisons of the biophysical properties and
      underlying mechanisms have only been rarely made between these two channels.
      However, the recent determination of their molecular structures by X-ray
      crystallography has revealed unexpected parallels in the architecture of the two
      pores, providing a basis for possible functional analogies. In this review, we
      analyze the structural and functional similarities that are shared by these
      trimeric ion channels, and we outline key unanswered questions that, if addressed
      experimentally, may help us to elucidate how two unrelated ion channels have
      adopted a similar fold of the pore.

PMID- 24937753
TI  - Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR)
      anion channel in the central nervous system.
AB  - Cell volume regulation (CVR) is essential for all types of cells in the central
      nervous system (CNS) to counteract cell volume changes that may be associated
      with neuronal activities or diseases and with osmosensing in the hypothalamus, to
      facilitate morphological changes during cell proliferation, differentiation and
      migration, and to execute apoptosis of cells. The regulation is attained by
      regulating the net influx or efflux of solutes and water across the plasma
      membrane. The volume-sensitive outwardly rectifying (VSOR) anion channel plays a
      major role in providing a pathway for anion flux during the regulation. The VSOR
      anion channel is permeable not only to Cl(-) ions but also to amino acids like
      glutamate and taurine. This property confers a means of intercellular
      communications through the opening of the channel in the CNS. Thus exploring the
      roles of VSOR anion channels is crucial to understand the basic principles of
      cellular functions in the CNS. Here we review biophysical and pharmacological
      characteristics of the VSOR anion channel in the CNS, discuss its activation
      mechanisms and roles in the CNS reported so far, and give some perspectives on
      the next issues to be examined in the near future. 

PMID- 24937755
TI  - microBEnet: lessons learned from building an interdisciplinary scientific
      community in the online sphere.

PMID- 24937754
TI  - Transient ischemic attack induced by melted solid lipid microparticles protects
      rat brains from permanent focal ischemia.
AB  - This study aims to develop a transient ischemic attack (TIA) model in conscious
      animals and uses this model to investigate the effect of TIA on subsequent
      permanent ischemia. TIA was induced by injecting designed temperature-sensitive
      melted solid lipid microparticles with a melting point around body temperature
      into male Wistar rats via arterial cannulation. Neurologic deficit was monitored
      immediately after the injection without anesthesia. According to the clinical
      definition of TIA, rats were divided into neurologic symptom durations <24-h, 24
      48-h and >=48-h groups. The lipid microparticle-induced infarct volumes were
      small in the <24-h and 24-48-h groups, while the volumes were five times larger
      in the >=48-h group. Permanent ischemic stroke was induced 3d after the induction
      of TIA by injecting a different kind of embolic particle manufactured by blending
      chitin and PLGA. The <24-h group had less severe neurologic deficits and smaller
      infarct volumes than that of 24-48-h and control (without prior lipid
      microparticle treatment) rats. Taken together, we successfully develop a TIA
      animal model which allows us to monitor the neurologic deficit in real-time. By
      adopting this model, we validate that TIA (<24h) preconditioning protects the
      brain from subsequent permanent ischemic stroke.

PMID- 24937756
TI  - Comparative analysis of deep-sea bacterioplankton OMICS revealed the occurrence
      of habitat-specific genomic attributes.
AB  - Bathyal aphotic ocean represents the largest biotope on our planet, which
      sustains highly diverse but low-density microbial communities, with yet untapped
      genomic attributes, potentially useful for discovery of new biomolecules,
      industrial enzymes and pathways. In the last two decades, culture-independent
      approaches of high-throughput sequencing have provided new insights into
      structure and function of marine bacterioplankton, leading to unprecedented
      opportunities to accurately characterize microbial communities and their
      interactions with the environments. In the present review we focused on the
      analysis of relatively few deep-sea OMICS studies, completed thus far, to find
      the specific genomic patterns determining the lifeway and adaptation mechanisms
      of prokaryotes thriving in the dark deep ocean below the depth of 1000m.
      Phylogenomic and omic studies provided clear evidence that the bathyal microbial
      communities are distinct from the epipelagic counterparts and, along with
      generally larger genomes, possess their own habitat-specific genomic attributes.
      The high abundance in the deep ocean OMICS of the systems for environmental
      sensing, signal transduction and metabolic versatility as compared to the
      epipelagic counterparts is thought to enable the deep-sea bacterioplankton to
      rapidly adapt to changing environmental conditions associated with resource
      scarcity and high diversity of energy and carbon substrates in the bathyal
      biotopes. Together with a versatile heterotrophy, mixotrophy and anaplerosis are
      thought to enable the deep-sea bacterioplankton to cope with these environmental
      conditions.

PMID- 24937757
TI  - Identification of genomic features in environmentally induced epigenetic
      transgenerational inherited sperm epimutations.
AB  - A variety of environmental toxicants have been shown to induce the epigenetic
      transgenerational inheritance of disease and phenotypic variation. The process
      involves exposure of a gestating female and the developing fetus to environmental
      factors that promote permanent alterations in the epigenetic programming of the
      germline. The molecular aspects of the phenomenon involve epigenetic
      modifications (epimutations) in the germline (e.g. sperm) that are transmitted to
      subsequent generations. The current study integrates previously described
      experimental epigenomic transgenerational data and web-based bioinformatic
      analyses to identify genomic features associated with these transgenerationally
      transmitted epimutations. A previously identified genomic feature associated with
      these epimutations is a low CpG density (<12/100bp). The current observations
      suggest the transgenerational differential DNA methylation regions (DMR) in sperm
      contain unique consensus DNA sequence motifs, zinc finger motifs and G-quadruplex
      sequences. Interaction of molecular factors with these sequences could alter
      chromatin structure and accessibility of proteins with DNA methyltransferases to
      alter de novo DNA methylation patterns. G-quadruplex regions can promote the
      opening of the chromatin that may influence the action of DNA methyltransferases,
      or factors interacting with them, for the establishment of epigenetic marks. Zinc
      finger binding factors can also promote this chromatin remodeling and influence
      the expression of non-coding RNA. The current study identified genomic features
      associated with sperm epimutations that may explain in part how these sites
      become susceptible for transgenerational programming. 

PMID- 24937758
TI  - Field validation of food outlet databases: the Latino food environment in North
      Carolina, USA.
AB  - OBJECTIVE: Obtaining valid, reliable measures of food environments that serve
      Latino communities is important for understanding barriers to healthy eating in
      this at-risk population. DESIGN: The primary aim of the study was to examine
      agreement between retail food outlet data from two commercial databases, Nielsen
      TDLinx (TDLinx) for food stores and Dun & Bradstreet (D&B) for food stores and
      restaurants, relative to field observations of food stores and restaurants in
      thirty-one census tracts in Durham County, NC, USA. We also examined differences
      by proportion of Hispanic population (</>=23.4 % Hispanic population) in the
      census tract and for outlets classified in the field as 'Latino' on the basis of
      signage and use of Spanish language. SETTING: One hundred and seventy-four food
      stores and 337 restaurants in Durham County, NC, USA. RESULTS: We found that
      overall sensitivity of food store listings in TDLinx was higher (64 %) than
      listings in D&B (55 %). Twenty-five food stores were characterized by auditors as
      Latino food stores, with 20 % identified in TDLinx, 52 % in D&B and 56 % in both
      sources. Overall sensitivity of restaurants (68 %) was higher than sensitivity of
      Latino restaurants (38 %) listed in D&B. Sensitivity did not differ substantially
      by Hispanic composition of neighbourhoods. CONCLUSIONS: Our findings suggest that
      while TDLinx and D&B commercial data sources perform well for total food stores,
      they perform less well in identifying small and independent food outlets,
      including many Latino food stores and restaurants.

PMID- 24937760
TI  - X-ray vs. NMR structure of N-terminal domain of delta-subunit of RNA polymerase.
AB  - The crystal structure of the N-terminal domain of the RNA polymerase delta
      subunit (Ndelta) from Bacillus subtilis solved at a resolution of 2.0A is
      compared with the NMR structure determined previously. The molecule crystallizes
      in the space group C222(1) with a dimer in the asymmetric unit. Importantly, the
      X-ray structure exhibits significant differences from the lowest energy NMR
      structure. In addition to the overall structure differences, structurally
      important beta sheets found in the NMR structure are not present in the crystal
      structure. We systematically investigated the cause of the discrepancies between
      the NMR and X-ray structures of Ndelta, addressing the pH dependence, presence of
      metal ions, and crystal packing forces. We convincingly showed that the crystal
      packing forces, together with the presence of Ni(2+) ions, are the main reason
      for such a difference. In summary, the study illustrates that the two structural
      approaches may give unequal results, which need to be interpreted with care to
      obtain reliable structural information in terms of biological relevance. 

PMID- 24937761
TI  - Ultrastructure and mineral composition of the cornea cuticle in the compound eyes
      of a supralittoral and a marine isopod.
AB  - The cuticle of the cornea in Crustacea is an interesting example of a composite
      material compromising between two distinct functions. As part of the dioptric
      apparatus of the ommatidia within the complex eye it forms transparent micro
      lenses that should as well maintain the mechanical stability of the head capsule.
      We analyzed the ultrastructure and composition of the isopod cornea cuticle of
      the terrestrial species Ligia oceanica and the marine Sphaeroma serratum. We used
      a variety of tissue preparation methods, electron microscopic techniques as well
      as electron microprobe analysis and Raman spectroscopic imaging. The results
      reveal various structural adaptations that likely increase light transmission.
      These are an increase in the thickness of the epicuticle, a reduction of the
      thickness of the outer layer of calcite, a spatial restriction of pore canals to
      interommatidial regions, and, for S. serratum only, an increase in calcite
      crystal size. In both species protein-chitin fibrils within the proximal
      exocuticle form a peculiar reticular structure that does not occur within the
      cuticle of the head capsule. In L. oceanica differential mineralization results
      in a spherically shaped interface between mineralized and unmineralized
      endocuticle, likely an adaptation to increase the refractive power of the cornea
      maintaining the mechanical stability of the cuticle between the ommatidia. The
      results show that the habitat and differences in the general structure of the
      animal's cuticle affect the way in which the cornea is adapted to its optical
      function.

PMID- 24937759
TI  - Antioxidant capacities, phenolic profile and cytotoxic effects of saxicolous
      lichens from trans-Himalayan cold desert of Ladakh.
AB  - Fourteen saxicolous lichens from trans-Himalayan Ladakh region were identified by
      morpho-anatomical and chemical characteristics. The n-hexane, methanol and water
      extracts of the lichens were evaluated for their antioxidant capacities. The
      lichen extracts showing high antioxidant capacities and rich phenolic content
      were further investigated to determine their cytotoxic activity on human HepG2
      and RKO carcinoma cell lines. The ferric reducing antioxidant power (FRAP), 2,2'
      azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 1,1
      diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging
      capacities and beta-carotene-linoleic acid bleaching property exhibited analogous
      results where the lichen extracts showed high antioxidant action. The lichen
      extracts were also found to possess good amount of total proanthocyanidin,
      flavonoid and polyphenol. The methanolic extract of Lobothallia alphoplaca
      exhibited highest FRAP value. Methanolic extract of Xanthoparmelia stenophylla
      showed the highest ABTS radical scavenging capacity. The n-hexane extract of
      Rhizoplaca chrysoleuca exhibited highest DPPH radical scavenging capacity.
      Highest antioxidant capacity in terms of beta-carotene linoleic acid bleaching
      property was observed in the water extract of Xanthoria elegans. Similarly,
      Melanelia disjuncta water extract showed highest NO scavenging capacity. Among n
      hexane, methanol and water extracts of all lichens, the methanolic extract of
      Xanthoparmelia mexicana showed highest total proanthocyanidin, flavonoid and
      polyphenol content. From cytotoxic assay, it was observed that the methanolic
      extracts of L. alphoplaca and M. disjuncta were exhibiting high cytotoxic effects
      against cancer cell growth. Similarly, the water extract of Dermatocarpon
      vellereum, Umbilicaria vellea, X. elegans and M. disjuncta and the methanolic
      extract of M. disjuncta and X. stenophylla were found to possess high antioxidant
      capacities and were non-toxic and may be used as natural antioxidants for stress
      related problems. Our studies go on to prove that the unique trans-Himalayan
      lichens are a hitherto untapped bioresource with immense potential for discovery
      of new chemical entities, and this biodiversity needs to be tapped sustainably. 

PMID- 24937762
TI  - An autoregulatory mechanism governing mucociliary transport is sensitive to mucus
      load.
AB  - Mucociliary clearance, characterized by mucus secretion and its conveyance by
      ciliary action, is a fundamental physiological process that plays an important
      role in host defense. Although it is known that ciliary activity changes with
      chemical and mechanical stimuli, the autoregulatory mechanisms that govern
      ciliary activity and mucus transport in response to normal and pathophysiological
      variations in mucus are not clear. We have developed a high-speed, 1-MUm
      resolution, cross-sectional imaging modality, termed micro-optical coherence
      tomography (MUOCT), which provides the first integrated view of the functional
      microanatomy of the epithelial surface. We monitored invasion of the periciliary
      liquid (PCL) layer by mucus in fully differentiated human bronchial epithelial
      cultures and full thickness swine trachea using MUOCT. We further monitored
      mucociliary transport (MCT) and intracellular calcium concentration
      simultaneously during invasion of the PCL layer by mucus using colocalized MUOCT
      and confocal fluorescence microscopy in cell cultures. Ciliary beating and mucus
      transport are up-regulated via a calcium-dependent pathway when mucus causes a
      reduction in the PCL layer and cilia height. When the load exceeds a
      physiological limit of approximately 2 MUm, this gravity-independent
      autoregulatory mechanism can no longer compensate, resulting in diminished
      ciliary motion and abrogation of stimulated MCT. A fundamental integrated
      mechanism with specific operating limits governs MCT in the lung and fails when
      periciliary layer compression and mucus viscosity exceeds normal physiologic
      limits. 

PMID- 24937763
TI  - Selective methyl labeling of eukaryotic membrane proteins using cell-free
      expression.
AB  - Structural characterization of membrane proteins and other large proteins with
      NMR relies increasingly on perdeuteration combined with incorporation of
      specifically protonated amino acid moieties, such as methyl groups of
      isoleucines, valines, or leucines. The resulting proton dilution reduces dipolar
      broadening producing sharper resonance lines, ameliorates spectral crowding, and
      enables measuring of crucial distances between and to methyl groups. While
      incorporation of specific methyl labeling is now well established for bacterial
      expression using suitable precursors, corresponding methods are still lacking for
      cell-free expression, which is often the only choice for producing labeled
      eukaryotic membrane proteins in mg quantities. Here we show that we can express
      methyl-labeled human integral membrane proteins cost-effectively by cell-free
      expression based of crude hydrolyzed ILV-labeled OmpX inclusion bodies. These are
      obtained in Escherichia coli with very high quantity and represent an optimal
      intermediate to channel ILV precursors into the eukaryotic proteins. 

PMID- 24937764
TI  - Discriminability measures and time-frequency features: an application to
      vibrissal tactile discrimination.
AB  - BACKGROUND: Often, the first problem that the neuroscientist must face is to
      determine if a specific stimulus set applied to biological system produces
      specific, precise and well differentiated responses. NEW METHOD: In the present
      study we have proposed four discriminability measures to evaluate the feasibility
      of differentiating experimental conditions: information measures based on
      information theory, percentage overlap based on Linacre method, Bhattacharyya
      distance and univariate standard distance. All discriminability measures were
      evaluated on experimental protocols related to vibrissal tactile discrimination.
      RESULTS: Time-frequency features were extracted from afferent discharges and
      then, pairwise comparisons were realized by using the proposed discriminability
      measures. Our results reveal the existence of time-frequency patterns which
      allows differentiating of sweep conditions from multifiber recordings. COMPARISON
      WITH EXISTING METHODS: Currently, statistical methods used to justify significant
      differences in experimental conditions have rigorous criteria that must be met
      for correct validation of results. Discriminability measures proposed here are
      robust and can be adjusted to different experimental conditions (time series,
      repeated measures, specific variables and other). CONCLUSIONS: Discriminability
      measures allowed determining the time intervals where two sweep situations have
      the highest probability to be differentiated from each other. High
      discriminability percentages were observed into protraction phase, although to a
      lesser degree, it was also observed in retraction phase. It was demonstrated that
      sensibility of discriminability measures are different. This revealing a greater
      ability to highlight percentage changes of pairwise comparisons. Finally, the
      methods here proposed can be adapted to other features of biological responses.

PMID- 24937765
TI  - Theoretical and practical applications of the intracerebroventricular route for
      CSF sampling and drug administration in CNS drug discovery research: a mini
      review.
AB  - Clinically, central nervous system (CNS) disorders account for more
      hospitalisations and prolonged care than almost all other diseases combined. In
      the preclinical setting, the intracerebroventricular (ICV) route for
      cerebrospinal fluid (CSF) sampling or dose administration in rodent models of
      human CNS disorders has potential to provide key insight on the pathobiology of
      these conditions. Low level neuroinflammation is present in >40% of patients with
      severe depression or schizophrenia and so comparative assessment of CSF
      composition between patients and rodent models of CNS disorders is potentially
      invaluable for hypothesis generation and for assessing rodent model validity. As
      molecules in the CSF have relatively low protein binding and are freely exchanged
      into the extracellular fluid of the brain parenchyma, supraspinal drug
      administration into the CSF can produce therapeutic drug concentrations in the
      brain. Direct administration of investigational agents into the CSF of the
      lateral ventricle of the brain enables intrinsic efficacy and adverse effect
      profiles to be evaluated without the confounding effects of drug metabolism, due
      to the low capacity of the CNS to metabolise exogenous compounds. It is our view
      that the ICV route for CSF sampling and for administration of novel drugs in
      development is under-utilised in preclinical research on CNS disorders. This is
      due to the high degree of technical skill and low margin for error associated
      with correct ICV guide cannula implantation in the rat. However, these technical
      challenges can be overcome by using standardised procedures and attention to
      detail during surgery and in the post-operative period. 

PMID- 24937766
TI  - Effect of amino acid ligands on the structure of iron porphyrins and their
      ability to bind oxygen.
AB  - Density functional theory is used to study a series of model iron porphyrins in
      the gas phase. In the first part of this study, three range-separated hybrid
      density functionals developed by Chai and Head-Gordon were assessed; omegaB97,
      omegaB97X, and omegaB97XD. The effects of including full Hartree-Fock exchange at
      long-range and dispersion corrections are reported with respect to the geometries
      and binding energies of oxygen to the iron porphyrin systems. The functionals all
      correctly predict the quintet ground state for the deoxy-iron porphyrins, where
      typically hybrid functionals fail and predict a triplet ground state. Including
      dispersion in omegaB97XD is shown to give the best results for the O2 binding
      energy and geometrical parameters. The second part of the study employs
      omegaB97XD to study iron porphine systems with different amino acids in the axial
      position. Geometrical parameters are reported and compared to experimental data,
      where available. Binding energies of the systems with oxygen are also reported
      and discussed. 

PMID- 24937768
TI  - Influence of light-induced conical intersection on the photodissociation dynamics
      of D2(+) starting from individual vibrational levels.
AB  - Previous works have shown that dressing of diatomic molecules by standing or by
      running laser waves gives rise to the appearance of so-called light-induced
      conical intersections (LICIs). Because of the strong nonadiabatic couplings, the
      existence of such LICIs may significantly change the dynamical properties of a
      molecular system. In our former paper (J. Phys. Chem. A 2013, 117, 8528), the
      photodissociation dynamics of the D(2)(+) molecule were studied in the LICI
      framework starting the initial vibrational nuclear wave packet from the
      superposition of all the vibrational states initially produced by ionizing D(2).
      The present work complements our previous investigation by letting the initial
      nuclear wave packets start from different individual vibrational levels of
      D(2)(+), in particular, above the energy of the LICI. The kinetic energy release
      spectra, the total dissociation probabilities, and the angular distributions of
      the photofragments are calculated and discussed. An interesting phenomenon has
      been found in the spectra of the photofragments. Applying the light-induced
      adiabatic picture supported by LICI, explanations are given for the unexpected
      structure of the spectra.

PMID- 24937767
TI  - A rational biomimetic approach to structure defect generation in colloidal
      nanocrystals.
AB  - Controlling the morphology of nanocrystals (NCs) is of paramount importance for
      both fundamental studies and practical applications. The morphology of NCs is
      determined by the seed structure and the following facet growth. While means for
      directing facet formation in NC growth have been extensively studied, rational
      strategies for the production of NCs bearing structure defects in seeds have been
      much less explored. Here, we report mechanistic investigations of high density
      twin formation induced by specific peptides in platinum (Pt) NC growth, on the
      basis of which we derive principles that can serve as guidelines for the rational
      design of molecular surfactants to introduce high yield twinning in noble metal
      NC syntheses. Two synergistic factors are identified in producing twinned Pt NCs
      with the peptide: (1) the altered reduction kinetics and crystal growth pathway
      as a result of the complex formation between the histidine residue on the peptide
      and Pt ions, and (2) the preferential stabilization of {111} planes upon the
      formation of twinned seeds. We further apply the discovered principles to the
      design of small organic molecules bearing similar binding motifs as
      ligands/surfactants to create single and multiple twinned Pd and Rh NCs. Our
      studies demonstrate the rich information derived from biomimetic synthesis and
      the broad applicability of biomimetic principles to NC synthesis for diverse
      property tailoring. 

PMID- 24937769
TI  - Pulsed electromagnetic field enhances brain-derived neurotrophic factor
      expression through L-type voltage-gated calcium channel- and Erk-dependent
      signaling pathways in neonatal rat dorsal root ganglion neurons.
AB  - Although pulsed electromagnetic field (PEMF) exposure has been reported to
      promote neuronal differentiation, the mechanism is still unclear. Here, we aimed
      to examine the effects of PEMF exposure on brain-derived neurotrophic factor
      (Bdnf) mRNA expression and the correlation between the intracellular free calcium
      concentration ([Ca(2+)]i) and Bdnf mRNA expression in cultured dorsal root
      ganglion neurons (DRGNs). Exposure to 50Hz and 1mT PEMF for 2h increased the
      level of [Ca(2+)]i and Bdnf mRNA expression, which was found to be mediated by
      increased [Ca(2+)]i from Ca(2+) influx through L-type voltage-gated calcium
      channels (VGCCs). However, calcium mobilization was not involved in the increased
      [Ca(2+)]i and BDNF expression, indicating that calcium influx was one of the key
      factors responding to PEMF exposure. Moreover, PD098059, an extracellular signal
      regulated kinase (Erk) inhibitor, strongly inhibited PEMF-dependant Erk1/2
      activation and BDNF expression, indicating that Erk activation is required for
      PEMF-induced upregulation of BDNF expression. These findings indicated that PEMF
      exposure increased BDNF expression in DRGNs by activating Ca(2+)- and Erk
      dependent signaling pathways. 

PMID- 24937772
TI  - Preparation of platinum modified titanium dioxide nanoparticles with the use of
      laser ablation in water.
AB  - We report on the preparation method of nanocrystalline titanium dioxide modified
      with platinum by using nanosecond laser ablation in liquid (LAL). Titania in the
      form of anatase crystals has been prepared in a two-stage process. Initially,
      irradiation by laser beam of a titanium metal plate fixed in a glass container
      filled with deionized water was conducted. After that, the ablation process was
      continued, with the use of a platinum target placed in a freshly obtained titania
      colloid. In this work, characterization of the obtained nanoparticles, based on
      spectroscopic techniques--Raman, X-ray photoelectron and UV-vis reflectance
      spectroscopy--is given. High resolution transmission electron microscopy was used
      to describe particle morphology. On the basis of photocatalytic studies we
      observed the rate of degradation process of methylene blue (MB) (a model organic
      pollution) in the presence of Pt modified titania in comparison to pure TiO2--as
      a reference case. Physical and chemical mechanisms of the formation of platinum
      modified titania are also discussed here. Stable colloidal suspensions containing
      Pt modified titanium dioxide crystalline anatase particles show an almost perfect
      spherical shape with diameters ranging from 5 to 30 nm. The TiO2 nanoparticles
      decorated with platinum exhibit much higher (up to 30%) photocatalytic activity
      towards the degradation of MB under UV illumination than pure titania.

PMID- 24937774
TI  - Partially crystalline Zn2GeO4 nanorod/graphene composites as anode materials for
      high performance lithium ion batteries.
AB  - Zn2GeO4 nanorod/graphene composites (ZGCs) were yielded by a two-step
      hydrothermal processing. Crystalline and amorphous regions were found to coexist
      in a single Zn2GeO4 nanorod. The surface of the Zn2GeO4 nanorod was compactly
      covered and anchored by graphene sheets. The ZGCs were then utilized as anodes
      for lithium ion batteries (LIBs). Intriguingly, partially crystalline ZGC
      containing 10.2 wt % graphene possessed excellent electrochemical performance,
      namely, high reversible capacity (1020 mA h g(-1) in the first cycle), favorable
      cyclic performance (768 mA h g(-1) after 50 cycles), and commendable rate
      capability (780 mA h g(-1) at the current density of 0.8A g(-1)). The amorphous
      region in partially crystalline Zn2GeO4 nanorods and the elastic graphene sheets
      provided the accommodation of volume change during the charge and discharge
      processes. These advantageous attributes make ZGCs the potential anode materials
      for LIBs. 

PMID- 24937770
TI  - MicroRNAs in cancer: glioblastoma and glioblastoma cancer stem cells.
AB  - MicroRNAs represent an abundant class of endogenously expressed 18-25 nucleotide
      non-coding RNA molecules that function to silence gene expression through a
      process of post-transcriptional modification. They exhibit varied and widespread
      functions during normal development and tissue homeostasis, and accordingly their
      dysregulation plays major roles in many cancer types. Gliomas are cancers arising
      from the central nervous system. The most malignant and common glioma is
      glioblastoma multiforme (GBM), and even with aggressive treatment (surgical
      resection, chemotherapy, and radiation), average patient survival remains less
      than 2 years. In this review we will summarize the current findings regarding
      microRNAs in GBM and the biological and clinical implications of this data.

PMID- 24937775
TI  - Nucleophilic addition/double cyclization cascade processes between enynyl Fischer
      carbene complexes and alkynyl malonates.
AB  - Two new selective cascade processes for enynyl Fischer carbene complexes 1 are
      described in their reaction with alkynyl malonates. When carbene complexes 1
      react with the sodium enolate of homopropargyl malonates 3 a consecutive Michael
      type addition/cyclopentannulation/6-exo cyclization takes place leading, in a
      regio- and stereoselective way, to n/5/6 angular tricyclic compounds 5.
      Furthermore, when propargylic malonates are used, a delayed protonation of the
      reaction mixture allows intermediate 1,4-addition adduct Ia to evolve through a 5
      exo cyclization, consisting of an intramolecular nucleophilic attack from the
      central carbon of the allenylmetallate over the triple C-C bond. Further
      spontaneous cyclopentannulation of the resulting metallatriene gives rise to
      bicyclic and linear polycyclic compounds 6 and 7, some of them bearing a
      polyquinane framework. 

PMID- 24937773
TI  - High mobility group box 1 (HMGB1) phenotypic role revealed with stress.
AB  - High mobility group box 1 (HMGB1) is an evolutionarily ancient protein that is
      present in one form or another in all eukaryotes. It fundamentally resides in the
      nucleus but translocates to the cytosol with stress and is subsequently released
      into the extracellular space. HMGB1 global knockout mice exhibit lethal
      hypoglycemia, whereas tissues and cells from conditional knockout or knock-in
      mice are born alive without apparent significant functional deficit. An aberrant
      response to targeted stress in the liver, pancreas, heart or myeloid cells is
      consistent with a protective role for HMGB1 in sustaining nuclear homeostasis and
      enabling other stress responses, including autophagy. Under some conditions,
      HMGB1 is not required for liver and heart function. Many challenges remain with
      respect to understanding the multiple roles of HMGB1 in health and disease. 

PMID- 24937776
TI  - Drp1 is dispensable for mitochondria biogenesis in induction to pluripotency but
      required for differentiation of embryonic stem cells.
AB  - Mature mitochondria with high oxidative phosphorylation undergo fission and
      fusion and morphogenesis to become immature mitochondria during induced
      pluripotent stem (iPS) induction from somatic cells. Dynamin-related protein 1
      (Drp1) is involved in mitochondria fission and biogenesis in somatic cells. We
      tested the role of Drp1 in the induction and maintenance of pluripotency. We show
      that Drp1 band shift occurs in embryonic stem cells (ESCs) and iPS cells (iPSCs)
      induced from fibroblasts, in association with mitochondrial morphogenesis.
      However, knockdown of Drp1 by shRNA does not abrogate mitochondria morphogenesis
      and induction of iPSCs from fibroblasts. Also, knockdown of Drp1 affects neither
      mitochondria fission and function as shown by normal mitochondrial membrane
      potential, nor proliferation and pluripotency of ESCs. Nonetheless, Drp1
      knockdown negatively influences terminal differentiation of ESCs, particularly in
      the lineage of neurogenesis in vitro and in vivo, coincident with delayed
      reduction of Oct4 and Nanog during mid-differentiation. Our data suggest that
      Drp1 is not critical for mitochondria biogenesis in stem cell proliferation but
      it is required for neurogenesis likely by downregulation of pluripotency
      associated genes Nanog and Oct4. ESC differentiation model could be used to model
      role of Drp1 in neuron development and diseases. 

PMID- 24937778
TI  - Central nervous system effects of whole-body proton irradiation.
AB  - Space missions beyond the protection of Earth's magnetosphere expose astronauts
      to an environment that contains ionizing proton radiation. The hazards that
      proton radiation pose to normal tissues, such as the central nervous system
      (CNS), are not fully understood, although it has been shown that proton radiation
      affects the neurogenic environment, killing neural precursors and altering
      behavior. To determine the time and dose-response characteristics of the CNS to
      whole-body proton irradiation, C57BL/6J mice were exposed to 1 GeV/n proton
      radiation at doses of 0-200 cGy and behavioral, physiological and
      immunohistochemical end points were analyzed over a range of time points (48 h-12
      months) postirradiation. These experiments revealed that proton radiation
      exposure leads to: 1. an acute decrease in cell division within the dentate gyrus
      of the hippocampus, with significant differences detected at doses as low as 10
      cGy; 2. a persistent effect on proliferation in the subgranular zone, at 1 month
      postirradiation; 3. a decrease in neurogenesis at doses as low as 50 cGy, at 3
      months postirradiation; and 4. a decrease in hippocampal ICAM-1 immunoreactivity
      at doses as low as 10 cGy, at 1 month postirradiation. The data presented
      contribute to our understanding of biological responses to whole-body proton
      radiation and may help reduce uncertainty in the assessment of health risks to
      astronauts. These findings may also be relevant to clinical proton beam therapy. 

PMID- 24937777
TI  - Coupling isotachophoresis with affinity chromatography for rapid and selective
      purification with high column utilization, part 2: experimental study.
AB  - We present an experimental study of coupling of isotachophoresis (ITP) and
      affinity chromatography (AC) to effect rapid, selective purification with high
      column utilization and high resolution. We provide a detailed protocol for
      performing ITP-AC and describe the design of a buffer system to perform sequence
      specific separation of nucleic acids. We describe the synthesis and
      functionalization of our affinity substrate, poly(glycidyl methacrylate-co
      ethylene dimethacrylate) porous polymer monolith (GMA-EDMA PPM). This substrate
      allows easy immobilization of affinity probes, is nonsieving (even to
      macromolecules), and exhibits negligible nonspecific binding. We demonstrate ITP
      AC with 25 nt, Cy5 labeled DNA target and a DNA probe and study the
      spatiotemporal dynamics using epifluorescence imaging. We make qualitative and
      quantitative comparisons between these data and the model presented in the first
      part of this two-paper series. We vary the target concentration from 1 pg MUL(-1)
      to 100 pg MUL(-1) and ITP velocity over the range of 10-50 MUm s(-1), and thereby
      explore over 4 orders of magnitude of scaled target amount. We observe very good
      agreement between predictions and experimental data for the spatiotemporal
      behavior of the coupled ITP and affinity process, and for key figures of merit,
      including scaled capture length and maximum capture efficiency. Lastly, we
      demonstrate that the resolution of ITP-AC increases linearly with time and purify
      25 nt target DNA from 10,000-fold higher abundance background (contaminating)
      genomic fish sperm DNA. We perform this capture from 200 MUL of sample in under 1
      mm column length and within <10 min.

PMID- 24937780
TI  - A microdosimetric-kinetic model for cell killing by protracted continuous
      irradiation II: brachytherapy and biologic effective dose.
AB  - Relationships based on the microdosimetric-kinetic model are presented that
      calculate the average number of lethal lesions, and the associated cell survival,
      produced in mammalian cells by exposure to protracted continuous irradiation by
      temporary and permanent implantation of radioactive sources. The influence of
      cell parameters of linear-quadratic survival, repair function and proliferation
      rate, as well as the influence of dose rate, isotopic decay rate and linear
      energy transfer (LET) quality on cell killing are displayed and discussed. An
      expression for biologic effective dose (BED) is presented that facilitates
      comparison of the effects of protracted low-dose-rate irradiation and with a
      course of multiple instantaneously administered radiation treatments (fractions).

PMID- 24937779
TI  - The optimal partnership of radiation and immunotherapy: from preclinical studies
      to clinical translation.
AB  - The main role of the immune system is to restore tissue homeostasis when altered
      by pathogenic processes, including neoplastic transformation. Immune-mediated
      tumor rejection has been recognized as an extrinsic tumor suppressor mechanism
      that tumors need to overcome to progress. By the time a tumor becomes clinically
      apparent it has successfully escaped immune control by establishing an
      immunosuppressive microenvironment. Ionizing radiation applied locally to a tumor
      alters these tumor-host interactions. Accumulating evidence indicates that
      standard therapeutic doses of radiation have the potential to recover tumor
      immunogenicity and convert the tumor into an in situ personalized vaccine.
      Radiotherapy induces an immunogenic tumor cell death promoting cross-presentation
      of tumor-derived antigens by dendritic cells to T cells. In addition,
      radiotherapy stimulates chemokine-mediated recruitment of effector T cells to the
      tumor, and cellular recognition and killing by T cells that is facilitated by
      upregulation of major histocompatibility antigens, NKG2D ligands, adhesion
      molecules and death receptors. Despite these effects, radiotherapy alone is only
      rarely capable of generating enough proinflammatory signals to sufficiently
      overcome suppression, as it can also activate immunosuppressive factors. However,
      our group and others have shown that when combined with targeted immunotherapy
      agents radiotherapy significantly contributes to a therapeutically effective anti
      tumor immune response. To illustrate this partnership between radiation and
      immunotherapy we will discuss as an example our experience in preclinical models
      and the molecular mechanisms identified. Additionally, the clinical translation
      of these combinations will be discussed. 

PMID- 24937781
TI  - A preclinical rodent model of acute radiation-induced lung injury after ablative
      focal irradiation reflecting clinical stereotactic body radiotherapy.
AB  - In a previous study, we established an image-guided small-animal micro
      irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The
      goal of this study was to develop a rodent model of acute phase lung injury after
      ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left
      lung of C57BL/6 mice using a small animal stereotactic irradiator. At days 1, 3,
      5, 7, 9, 11 and 14 after irradiation, the lungs were perfused with formalin for
      fixation and paraffin sections were stained with hematoxylin and eosin (H&E) and
      Masson's trichrome. At days 7 and 14 after irradiation, micro-computed tomography
      (CT) images of the lung were taken and lung functional measurements were
      performed with a flexiVentTM system. Gross morphological injury was evident 9
      days after irradiation of normal lung tissues and dynamic sequential events
      occurring during the acute phase were validated by histopathological analysis. CT
      images of the mouse lungs indicated partial obstruction located in the peripheral
      area of the left lung. Significant alteration in inspiratory capacity and tissue
      damping were detected on day 14 after irradiation. An animal model of radiation
      induced lung injury (RILI) in the acute phase reflecting clinical stereotactic
      body radiotherapy was established and validated with histopathological and
      functional analysis. This model enhances our understanding of the dynamic
      sequential events occurring in the acute phase of radiation-induced lung injury
      induced by ablative dose focal volume irradiation. 

PMID- 24937783
TI  - Editorial.

PMID- 24937784
TI  - Is there a differential efficacy of new generation antipsychotic drugs?

PMID- 24937782
TI  - Early-delayed, radiation-induced cognitive deficits in adult rats are
      heterogeneous and age-dependent.
AB  - Patients treated with whole-brain irradiation often develop cognitive deficits
      that are presumed to result from normal tissue injury. Age is a risk factor for
      these side effects. We compared the cognitive effects of fractionated whole-brain
      irradiation (300 kV X rays) in rats irradiated either as young adults or in
      middle age. A deficit in object memory was apparent at 3 months in rats
      irradiated as young adults, however, no comparable deficit was apparent in rats
      irradiated in middle age. In addition, the deficit in object memory in young
      adults was no longer apparent at 6 and 12 months after fractionated whole-brain
      irradiation and no radiation-induced deficit was detectable in a spatial memory
      task at any time, regardless of age at time of irradiation. Thus, clinically
      relevant fractionated whole-brain irradiation in adult rats resulted in early
      delayed cognitive changes that were heterogeneous, transient and age-dependent.
      The results of the current and previous studies of radiation-induced cognitive
      changes support the continued investigation and validation of rodent models of
      radiation-induced brain injury, which are critical for developing and testing new
      therapies for treatment-induced cognitive dysfunction in cancer survivors. 

PMID- 24937785
TI  - The relationship between depression and cardiovascular disease.
AB  - Evidence from epidemiological studies has established that depression is a risk
      factor for the development of cardiovascular disease (CVD) and that the
      comorbidity of depression with pre-existing CVD worsens the prognosis for
      sufferers of CVD. Depression has also been associated with other behaviours that
      impact on CVD, such as medication non-compliance, and an unwillingness to adopt
      an exercise program, that reduce the likelihood of successful rehabilitation from
      CVD. Published literature on the current knowledge of the association between
      depression and CVD is reviewed in this paper. 

PMID- 24937786
TI  - Driving ability in schizophrenic patients: effects of neuroleptics.
AB  - Recent studies indicate that individuals with schizophrenia have a two-fold
      incidence of traffic accidents. Cognitive and psychomotor impairment as a core
      feature of schizophrenia and the effects of neuroleptic treatment play an
      essential role in this respect. Few experimental studies have been conducted so
      far looking at the effects of neuroleptics on driving ability in schizophrenia.
      Controlled, randomised trials are totally missing. The limited database indicates
      that most schizophrenic patients show significant impairment in cognitive
      functions relevant for driving ability compared to healthy controls. There is
      some but limited evidence that patients under novel atypical neuroleptics show
      less impairment compared to conventional neuroleptics. More clinical and
      experimental studies are warranted. 

PMID- 24937787
TI  - Treatment practice of acute mania and bipolar depression: a nation-wide
      questionnaire survey in Finland.
AB  - Objective To compare Finnish clinicians' treatment practices of acute mania and
      bipolar depression with recommendations of consensus-based guidelines, and
      contemporary research results. Methods A nation-wide questionnaire survey of 228
      Finnish clinicians employed in psychiatric hospitals. Results Effective response
      rate was 62%. Clinicians' practices were fairly adequately in line with
      contemporary recommendations. The main concerns were over-utilization of
      conventional antipsychotics in acute mania and underestimating the need for mood
      stabilizers to prevent induction of mood instability. Conclusion Continuous
      educating of clinicians is warranted to narrow the gap between guideline
      recommendations, research evidence and clinical practices. 

PMID- 24937788
TI  - Quetiapine in patients with borderline personality disorder and psychosis: a case
      series.
AB  - Objective Atypical antipsychotics appear to be effective and well tolerated in
      the treatment of borderline personality disorder. One such agent, quetiapine
      ("Seroquel"), has a favourable side-effect profile and may be of value in acute
      and chronic treatment of this disorder. Methods In this case series, 12
      outpatients with psychotic disorders meeting ICD-10, DSM-IV and DIB-R criteria
      for borderline personality disorder were treated with quetiapine monotherapy 300
      750 mg/day. The CGI-S and the GAS assessed changes in symptom severity and global
      functioning, whereas the BIS, the HAM-D and the SCL-90-IX scales assessed change
      of psychotic symptoms and/or borderline personality disorder core symptomatology
      over time. Patients were evaluated at baseline and at 4 and 12 weeks after
      treatment. Statistical analyses included Page's trend test and Wilcoxon tests.
      Results All patients completed the 12-week study. The mean quetiapine dose was
      537.5+/-18.9 mg/day. For all efficacy measures (with the exception of HAM-D),
      significant improvements were observed as early as Week 4 (P<0.01) and at
      endpoint (P<0.05). Conclusion Quetiapine relieved symptoms of psychosis, reduced
      impulsivity or depressed mood and improved global functioning in patients with
      borderline personality disorder and psychosis. Quetiapine was well tolerated. 

PMID- 24937789
TI  - Psychiatric symptoms and diagnoses in thyroid disorders: a cross-sectional study.
AB  - Objective Endocrine dysfunction may produce symptoms that are difficult to
      distinguish from the clinical manifestations of psychiatric disorders. In
      particular, the function of the hypothalamic-pituitary-thyroidal axis is known to
      be associated with a number of psychiatric abnormalities, such as depression and
      anxiety. In this study, we tested the hypothesis that depression is more commonly
      encountered in hypothyroidism, while anxiety is more prevalent in
      hyperthyroidism. Additionally, we aimed to evaluate the correlations of the
      intensity of the psychiatric symptomatology in these patients with the specific
      parameters of thyroid function, such as levels of TSH, T3 and T4. Method Patients
      newly diagnosed as having thyroid disorders were included in the study. They were
      classified into five study groups (according to the results of thyroid
      stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and
      autoantibody (anti-thyroglobulin antibodies and anti-microsomal antibodies)
      measurements): hypothyroid, hyperthyroid, subclinical hypothyroid, subclinical
      hyperthyroid, and euthyroid Hashimoto's thyroiditis. Psychopathological symptoms
      were evaluated on the 17-item Hamilton Rating Scale for Depression (HDRS), Brief
      Symptom Inventory (BSI), BSI Sub-scales and Hospital Anxiety and Depression Scale
      (HAD). Psychiatric diagnoses were performed using DSM-IV-SCID (Structured
      Clinical Interview for DSM). The relationship between the results of the
      psychiatric evaluation and thyroid function tests was assessed statistically by
      ANOVA and Pearson correlation tests. Results Eighty patients (68 female and 12
      male), with a mean age of 42.5+/-13.4 years, were evaluated. A positive
      correlation between the total BSI scores and TSH levels (r = 0.65, P = 0.01) was
      noted in the hypothyroid (n=25) group. Hyperthyroid patients (n=22) showed a
      positive correlation between HDRS scores and fT4 levels (r = 0.62, P = 0.01). The
      BSI scores in hypo- and hyperthyroidism were significantly higher than normal
      (P<0.05). In the subclinical hypothyroid (n=7), subclinical hyperthyroid (n=11),
      and euthyroid Hashimoto's thyroiditis (n=15) groups no correlation was found
      between thyroid function tests and HDRS, BSI, and HAD scores. Conclusion The
      results indicate that patients with thyroid disorders have high levels of anxiety
      and depressive symptoms. Thirty-five patients (43%) out of 80 had an axis I
      psychiatric disorder. However, our findings did not support an association
      between high levels of depression and hypothyroidism or between high levels of
      anxiety and hyperthyroidism. Moreover, this study did not reveal any specific
      psychiatric manifestation of hypothyroidism or hyperthyroidism. 

PMID- 24937790
TI  - Effect of milnacipran on insight and stress coping strategy in patients with
      Taijin Kyofusho.
AB  - Objective Taijin-Kyofusho (TKS) is a Japanese culture-bound syndrome similar to
      social anxiety disorder. Recent studies have shown antidepressants to be
      effective in treating TKS. The effects on insight or coping strategies have not,
      however, been studied. The present study investigated changes in insight and
      stress coping strategies during treatment with milnacipran. Method The study was
      a 12-week open trial in 16 patients with offensive type TKS. Offensive anxiety
      was assessed by an original TKS scale. Insight regarding TKS symptoms was
      assessed by the "Insight into obsessions and compulsions" subscale of the Yale
      Brown Obsessive Compulsive Scale. Coping strategies were assessed by the Coping
      Inventory for Stressful Situations. The primary efficacy variable was global
      improvement on the Clinical Global Impression scale (CGI). Results Of the sixteen
      patients, only 10 completed the study and seven patients responded to the drug (a
      score of 2 or less on CGI at endpoint). Six patients dropped out in the first few
      days because of nausea. Last observation carried forward analysis (N=16) showed a
      significant reduction of offensive anxiety of TKS. Insight and emotional coping
      strategies were also significantly improved. Conclusion The results suggested
      that not only TKS symptoms, but also insight and stress coping, may be improved
      by treatment with milnacipran. 

PMID- 24937791
TI  - Effectiveness of quetiapine for the management of aggressive psychosis in the
      emergency psychiatric setting: a naturalistic uncontrolled trial.
AB  - Objective Traditionally, conventional antipsychotics, often administered
      intramuscularly, are used to reduce hostility and aggression in the emergency
      setting. This study investigated the efficacy of quetiapine, an oral atypical
      antipsychotic, in managing aggressive psychosis. Methods Adult hospitalized
      patients (n=36) with an Overt Aggression Scale (OAS) total score >=1 and a Brief
      Psychiatric Rating Scale-derived Psychosis Index score >=6 received 100-800
      mg/day flexibly dosed quetiapine and were monitored daily for a maximum of 5
      days. The OAS total score and Physical Aggression Against Others subscale score
      were primary efficacy assessments. Tolerability was assessed with the Udvalg for
      Kliniske Undersogelser Side Effects Rating Scale. Results An 83% decrease in the
      OAS Physical Aggression Against Others subscale score occurred from Day 1
      (baseline) to Day 2, which was generally maintained to Day 5; a 39% reduction in
      OAS total score was observed by Day 2. The OAS total score decreased from a mean
      baseline of 3.3 to 1.5 at Day 5, a significant decrease for Days 2-4 (P < 0.01)
      and of borderline significance on Day 5 (P=0.059). Adverse events were mostly
      mild to moderate with concentration difficulties and somnolence the most common.
      Conclusion These results from an uncontrolled trial suggest that quetiapine may
      be helpful for some aggressive patients in the emergency setting. 

PMID- 24937792
TI  - Comparing efficacy of first-line atypical antipsychotics: no evidence of
      differential efficacy between risperidone, olanzapine, quetiapine, ziprasidone,
      and aripiprazole.
AB  - Objective To evaluate the comparative efficacy of the first-line atypical
      antipsychotics risperidone, olanzapine, quetiapine, ziprasidone, and
      aripiprazole. Methods We reviewed published short-term, randomised, controlled
      clinical trials of first-line atypical antipsychotics in the treatment of
      schizophrenia or schizoaffective disorder that used the Positive and Negative
      Syndrome Scale to assess efficacy. We used a combined overview analysis to
      compare the extent of improvement in global symptoms and positive and negative
      symptoms. We did not analyse adverse event data. Results Although we found
      considerable variation in the degree of improvement with a particular atypical
      antipsychotic across different studies, the range and average improvement were
      similar among all first-line atypicals for all efficacy parameters considered.
      Dosage was a critical determinant of efficacy, although the most effective dose
      of each agent varied across studies. There were insufficient data for ziprasidone
      and aripiprazole to allow their inclusion in the formal overview comparison.
      Conclusion Despite confounding and methodological limitations, the data we
      reviewed do not support assertions of differential efficacy between the first
      line atypical antipsychotics. Additional controlled comparative studies of the
      atypical antipsychotics should be of particular interest. 

PMID- 24937793
TI  - Emotional states and informational brain processing in drug addicts free of
      drugs: An ERPs study.
AB  - Objective To analyze brain event-related responses in heroin-dependent patients
      under different emotional conditions, in order to determine the influence of
      specific emotional loading on information processing in drug addicts. Methods
      Fifteen male heroin-dependent patients, matched to 11 male healthy individuals,
      were exposed to emotion-triggering slides designed to elicit neutral, pleasant or
      unpleasant emotions, while ERPs were obtained by means of an auditory oddball
      paradigm. Evoked potential analysis consisted of measuring the amplitude,
      latency, and topographic distribution (mapped from 19 scalp sites) of the early
      and late latency component waveforms. Results Both groups showed large-amplitude,
      long-latency, and positive-polarity responses to odd stimuli under all emotional
      conditions. A within-group comparison between the three emotional conditions
      showed that the control group had smaller P300 amplitudes under pleasant
      stimulation; drug addicts showed no differences between all three emotional
      conditions. Between-group analysis revealed smaller P300 amplitudes in drug
      addicts than in controls, both for unpleasant and neutral emotional conditions,
      but this was only significant for some electrode sites. Brain electrical activity
      mapping at P300 showed that high activation is less spread in the brain areas of
      drug addicts than in controls for unpleasant and neutral emotional conditions.
      Conclusion Drug addicts have deficits in extracting relevant information from
      sensory stimuli under different emotional conditions, particularly under
      unpleasant and neutral stimulation. Decreased P300 in controls under pleasant
      stimulation is interpreted as a result of an attentional bias mechanism that
      directs attentional resources to environmental stimuli of positive emotional
      valence, in contrast to drug addicts where there is no such effect. 

PMID- 24937794
TI  - Risk factors of attempted suicide in the elderly: The role of cognitive
      impairment.
AB  - The authors' aim was to assess the prevalence and importance of dementia and
      cognitive impairment in relation to suicidal behaviour in elderly psychiatric
      inpatients. The level of cognitive functioning (according to the Mini Mental
      State Examination - MMSE) of the elderly suicidal inpatients (N=62) were compared
      to the general elderly inpatients (N=152). There were significant differences in
      cognitive functioning between the two groups, in the non-suicidal group the level
      of cognitive function was significantly lower. However, mild cognitive deficit or
      mild dementia were registered in 60% of the suicide attempters. The results
      indicate that not only mood disorders, but other risk factors (especially mild
      cognitive impairment), have a key role in developing suicidal behaviour in the
      elderly. Thus, in the treatment and prevention of suicidal behaviour in the
      elderly, it is important to apply the complex bio-psycho-social model, in which
      (besides adequate pharmacotherapy) psychotherapeutic approaches and procedures to
      enhance cognitive functioning are of outstanding significance. 

PMID- 24937795
TI  - Frequency-dependent effects of contralateral repetitive transcranial magnetic
      stimulation on penicillin-induced seizures.
AB  - Transcranial magnetic stimulation (TMS) has been shown to modulate multiple brain
      functions, warranting further exploration in clinical applications. TMS treatment
      for epilepsy is particularly promising because of its anti-convulsive
      capabilities. However, TMS has been found to both inhibit and facilitate various
      experimental and clinical seizures, depending on the TMS parameters used.
      Repetitive TMS (rTMS) pulse frequency is recognized as one of the most
      influential parameters and thus was investigated in this study at 1, 5 and 10 Hz
      for its effects on a rat model of penicillin-induced seizures. High-dose
      penicillin-induced seizures were characterized by a combination of myoclonic and
      tonic-clonic (GTC) seizures. rTMS effects were analyzed with intracranial
      electroencephalographic (iEEG) data and video-captured behaviors. Animals treated
      with 1 and 5 Hz consistently showed evidence of anti-convulsive properties in
      their iEEG-based seizure profiles when compared to sham rTMS treatment. In
      contrast, data from 10 Hz rTMS suggested facilitative characteristics. Our
      results showed that 5 Hz rTMS consistently outperformed 1 Hz rTMS in seizure
      suppression. This re-emphasizes the importance in accurately characterizing TMS
      effects on seizure suppression due to the heterogeneous nature of seizures. Thus,
      finely tuned TMS treatment has great potential to become a powerful asset in
      combating epilepsy.

PMID- 24937796
TI  - Coaggregation of Two Anionic Azo Dyestuffs: A Combined Static Light Scattering
      and Small-Angle X-ray Scattering Study.
AB  - The formation of azo dyestuff aggregates in dilute aqueous solution induced by
      the addition of Mg2+, Ca2+, Sr2+, or Ba2+ ions is followed by time-resolved
      static light scattering (SLS) and time-resolved small-angle X-ray scattering
      (SAXS). Time-dependent molar mass data of the growing aggregates is interpreted
      by means of a kinetic model introduced by Lomakin et al. ( Proc. Natl. Acad. Sci.
      U.S.A. 1996 , 93 , 1125 ) for the description of beta-amyloid aggregation. This
      interpretation reveals significant trends within the homologous series of
      alkaline earth cations. The trends refer to the nucleation and the growth rate of
      the dyestuff fibers. Time-resolved SAXS experiments indicate that these first two
      stages are followed by a third one during which a network forms by partial
      lateral alignment of fibers. At high enough dyestuff concentrations, this network
      formation even leads to a gel-like phase. Anomalous SAXS (ASAXS) on such a gel
      phase formed upon the addition of Sr2+ revealed the extent of neutralization of
      the dyestuff molecules within the gel by the specifically interacting alkaline
      earth cations.

PMID- 24937797
TI  - Is there a difference in neurologic outcome in medical versus early operative
      management of cervical epidural abscesses?
AB  - BACKGROUND CONTEXT: The ideal management of cervical spine epidural abscess
      (CSEA), medical versus surgical, is controversial. The medical failure rate and
      neurologic consequences of delayed surgery are not known. PURPOSE: The purpose of
      this study is to assess the neurologic outcome of patients with CSEA managed
      medically or with early surgical intervention and to identify the risk factors
      for medical failure and the consequences of delayed surgery. STUDY
      DESIGN/SETTING: Retrospective electronic medical record (EMR) review. PATIENT
      SAMPLE: Sixty-two patients with spontaneous CSEA, confirmed with advanced
      imaging, from a single tertiary medical center from January 5 to September 11.
      OUTCOME MEASURES: Patient data were collected from the EMR with motor scores (MS)
      (American Spinal Injury Association 0-100) recorded pre/posttreatment. Three
      treatment groups emerged: medical without surgery, early surgery, and those
      initially managed medically but failed requiring delayed surgery. METHODS:
      Inclusion criteria: spontaneous CSEA based on imaging and intraoperative findings
      when available, age >18 years, and adequate EMR documentation of the medical
      decision-making process. Exclusion criteria: postoperative infections, Pott
      disease, isolated discitis/osteomyelitis, and patients with imaging findings
      suggestive of CSEA but negative intraoperative findings and cultures. RESULTS: Of
      the 62 patients included, 6 were successfully managed medically (Group 1) with MS
      increase of 2.3 points (standard deviation [SD] 4.4). Thirty-eight patients were
      treated with early surgery (Group 2) (average time to operating room 24.4 hours
      [SD 19.2] with average MS increase 11.89 points [SD 19.5]). Eighteen failed
      medical management (Group 3) requiring delayed surgery (time to OR 7.02 days [SD
      5.33]) with a net MS drop of 15.89 (SD 24.9). The medical failure rate was 75%.
      MS change between early and delayed surgery was significant (p<.001) favoring
      early surgery. Risk factors and laboratory data did not predict medical failure
      or posttreatment MS because of the high number of medical failures when abscess
      involves the cervical epidural space. CONCLUSIONS: Early surgery results in
      improved posttreatment MS compared with medical failure and delayed surgery. In
      our patients, the failure rate of medical management was high, 75%. Based on our
      results, we recommend early surgical decompression for all CSEA.

PMID- 24937798
TI  - Traumatic atlantoaxial dislocation with an old Type II odontoid fracture.

PMID- 24937799
TI  - Posterolateral lumbar fusion using Escherichia coli-derived rhBMP
      2/hydroxyapatite in the mini pig.
AB  - BACKGROUND CONTEXT: Hydroxyapatite (HA) is used as a bone graft extender for
      posterolateral spinal fusion in human. It is also useful as a recombinant human
      bone morphogenetic protein (rhBMP)-2 carrier because of its high affinity for
      rhBMP-2. PURPOSE: To assess the osteoinductivity of Escherichia coli-derived
      rhBMP-2 (E-BMP-2) using HA granules as a carrier and to evaluate the bone-forming
      ability depending on the different dosages of E-BMP-2. STUDY DESIGN: A mini-pig
      lumbar posterolateral fusion model using microcomputed tomography (MUCT)
      scanning. PATIENT SAMPLE: Thirty-one adult male mini pigs were randomized into a
      single control group (n=8) without E-BMP-2 and two experimental groups with two
      different doses of E-BMP-2 (1 mg per side, n=8 and 3 mg per side, n=15). OUTCOME
      MEASURES: Outcome was measured by plain radiography, manual palpation, CT, three
      dimensional MUCT, and histologic examinations. METHODS: Bilateral intertransverse
      process arthrodesis was performed, and E-BMP-2 (0, 1.0, 3.0 mg per side) was
      implanted into the intertransverse space using HA granules as a carrier. RESULTS:
      Three mini pigs were removed because of death. Among 28 experimental subjects, 19
      animals achieved solid bony union. The fusion rates were 37.5% for control group,
      71.4% for 1 mg group, and 84.6% for 3 mg group. Fusion rates were significantly
      different among groups (p=.031). However, there was no statistically significant
      difference in fusion rates between 1 and 3 mg groups (p=.587). Thirty-eight
      intertransverse fusion masses of 19 subjects underwent MUCT scanning. The bone
      volumes determined by MUCT were 12,603+/-3,240 mm(3) for control group, 18,718+/
      3,000 mm(3) for 1 mg group, and 26,768+/-7,256 mm(3) for 3 mg group, and the
      difference between groups was statistically significant (p<.001). CONCLUSIONS:
      This study shows that E-BMP-2 has osteoinductive activity in dose-dependent
      fashion, and porous HA granule is suitable for E-BMP-2 carrier in a porcine
      posterolateral fusion model. These preliminary findings suggest that E-BMP-2
      adsorbed porous HA granules could be a novel effective bone graft substitute.

PMID- 24937800
TI  - Species coexistence in a lattice-structured habitat: effects of species dispersal
      and interactions.
AB  - Opinions differ on how the spatial distribution of species over space affects
      species coexistence. Here, we constructed both mean-field and pair approximation
      (PA) models to explore the effects of interspecific and intraspecific
      interactions and dispersal modes on species coexistence. We found that spatial
      structure resulting from species dispersal traits and neighboring interactions in
      PA model did not promote coexistence if two species had the same traits, though
      it might intensify the contact frequency of intraspecific competition. If two
      species adopt different dispersal modes, the spatial structure in PA would make
      the coexistence or founder control less likely since it alters the species
      effective birth rate. This suggests that the spatial distribution caused by
      neighboring interactions and local dispersal does not affect species coexistence
      unless it adequately alters the effective birth rate for two species. Besides, we
      modeled how the initial densities and patterns affected population dynamics and
      revealed how the final spatial pattern was generated. 

PMID- 24937801
TI  - On the origin of immunopathology.
AB  - Stranded between medicine and experimental biology, immunology is buried in its
      own problems and remains distant from important areas of current biology, such as
      evolutionary theory, developmental biology and cognitive sciences. Immunology has
      treated the living system merely as the place or dimension in which immune
      activity takes place, inserted on a misleading axis (progressive responsiveness
      versus no response; memory versus tolerance) which neglects the analysis of a
      robustly stable dynamics which is always present and is neither tolerance nor
      immunity-a problem currently approached as one of "regulatory" activity. However,
      a regulatory response also demands regulation, leading to an endless recursion
      and the adoption of a stimulus-response framework inevitably drives us away from
      the physiological processes in which lymphocytes are involved. Herein, we propose
      that immunological physiology, like everything else in the body is dynamic and
      conservative. Immunopathology, including inherited immunodeficiencies, severe
      forms of infectious diseases, allergy and autoimmune diseases, are interferences
      with this stability which frequently include oligoclonal expansions of T
      lymphocytes. We suggest that this decrease in clonal diversity results from a
      loss of the stabilizing connectivity among lymphocytes and are not simply markers
      of immunopathology, but are rather expressions of basic pathogenic mechanisms.
      The so-called autoimmune diseases are examples of this disequilibrium. In the
      last decade the characterization of an enormous and diversified commensal
      microbiota has posed a new and pressing problem: how to explain the harmonic
      conviviality with trillions of foreign macromolecules. In addition, robustly
      stable relations towards macromolecular diet can be established by simple
      ingestion, a state presently labeled as "oral tolerance", a problem that has been
      buffered for decades as anti-inflammatory protection of the gut. A major change
      in terminology is necessary to describe this new panorama. We focus on two
      important gaps in immunological discussions: (a) the organism, seen
      simultaneously as the medium with which the immune system is constantly in touch
      and as the entity that mediates the contact with external materials; and (b) the
      observer, the immunologist, who operates as a human being in human languaging
      with other human beings, and characterizes immunological specificity. We
      acknowledge that we are proposing radical departures from current dogma and that
      we should justify them. Most of what we propose stem form a way of seeing called
      Biology of Cognition and Language, that derives from ideas of the
      neurobiologist/philosopher Humberto Maturana, also known as "autopoiesis theory".

PMID- 24937802
TI  - The MTMR9 rs2293855 polymorphism is associated with glucose tolerance, insulin
      secretion, insulin sensitivity and increased risk of prediabetes.
AB  - BACKGROUND: Polymorphism of rs2293855 in gene MTMR9 has been associated with
      obesity and metabolic syndrome. We aim to study the association of rs2293855 with
      type 2 diabetes mellitus (T2DM) intermediate phenotypes in a Han Chinese
      population. METHODS: The polymorphism was genotyped in 838 Han Chinese
      individuals using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass
      Spectrometry (MALDI-TOF MS); all participants underwent a 75 g oral glucose
      tolerance test (OGTT); associations between the polymorphism and glucose
      tolerance, indices of insulin secretion and indices of insulin sensitivity were
      analyzed. RESULTS: The frequency of genotypes and alleles differed significantly
      between normal glucose tolerance and prediabetes (P=0.043 and P=0.009,
      respectively). The GG homozygous presented higher fasting plasma glucose
      (P=0.009), higher 2-hour plasma glucose (P=0.024) and higher glucose area under
      the curve (AUC, P=0.01). Moreover, the G allele of rs2293855 was associated with
      glucose intolerance (fasting glucose, P=0.012; glucose AUC, P=0.006; 2-h glucose,
      P=0.024); it is also associated with decreased indices of insulin sensitivity
      (fasting insulin, P=0.043; insulin sensitivity index composite, P=0.009;
      homeostasis model assessment of insulin resistance, HOMA-IR, P=0.008) and
      decreased indices of insulin secretion (HOMA of beta cell function, HOMA-B,
      P=0.028; insulinogenic index, P=0.003). In addition, the minor allele G was also
      associated with increased risk of prediabetes (OR=1.463, 95%CI: 1.066-2.009,
      P=0.018). CONCLUSIONS: Polymorphism of rs2293855 in MTMR9 is associated with
      measures of glucose tolerance, indices of insulin secretion and indices of
      insulin sensitivity. We also suggest that allele G is likely to increase the risk
      of prediabetes by influencing both insulin secretion and insulin sensitivity.

PMID- 24937803
TI  - Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1;
      q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male.
AB  - It is widely accepted that the incidence of chromosomal aberration is 10-15.2% in
      the azoospermic male; however, the exact genetic damages are currently unknown
      for more than 40% of azoospermia. To elucidate the causative gene defects, we
      used the next generation sequencing (NGS) to map the breakpoints of a chromosome
      insertion from an azoospermic male who carries a balanced, maternally inherited
      karyotype 46, XY, inv ins (18,7) (q22.1; q36.2q21.11). The analysis revealed that
      the breakage in chromosome 7 disrupts two genes, dipeptidyl aminopeptidase-like
      protein 6 (DPP6) and contactin-associated protein-like 2 (CACNA2D1), the former
      participates in regulation of voltage-gated potassium channels, and the latter is
      one of the components in voltage-gated calcium channels. The deletion and
      duplication were not identified equal or beyond 100 kb, but 4 homologous DNA
      elements were verified proximal to the breakpoints. One of the proband's sisters
      inherited the same aberrant karyotype and experienced recurrent miscarriages and
      consecutive fetus death, while in contrast, another sister with a normal
      karyotype experienced normal labor and gave birth to healthy babies. The
      insertional translocation is confirmed with FISH and the Y-chromosome
      microdeletions were excluded by genetic testing. This is the first report
      describing chromosome insertion inv ins (18,7) and attributes DPP6 and CACNA2D1
      to azoospermia.

PMID- 24937804
TI  - Comparison of trends in tuberculosis incidence among adults living with HIV and
      adults without HIV--Kenya, 1998-2012.
AB  - BACKGROUND: In Kenya, the comparative incidences of tuberculosis among persons
      with and without HIV have not been described, and the differential impact of
      public health interventions on tuberculosis incidence in the two groups is
      unknown. METHODS: We estimated annual tuberculosis incidence stratified by HIV
      status during 2006-2012 based on the numbers of reported tuberculosis patients
      with and without HIV infection, the prevalence of HIV infection in the general
      population, and the total population. We also made crude estimates of annual
      tuberculosis incidence stratified by HIV status during 1998-2012 by assuming a
      constant ratio of HIV prevalence among tuberculosis patients compared to the
      general population. RESULTS: Tuberculosis incidence among both adults with HIV
      and adults without HIV increased during 1998-2004 then remained relatively stable
      until 2007. During 2007-2012, tuberculosis incidence declined by 28-44% among
      adults with HIV and by 11-26% among adults without HIV, concurrent with an
      increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among
      adults with HIV (1,839-1,936 cases/100,000 population) was still eight times as
      high as among adults without HIV (231-238 cases/100,000 population), and
      approximately one third of tuberculosis cases were attributable to HIV.
      CONCLUSIONS: Although tuberculosis incidence has declined among adults with and
      without HIV, the persistent high incidence of tuberculosis among those with HIV
      and the disparity between the two groups are concerning. Early diagnosis of HIV,
      early initiation of antiretroviral therapy, regular screening for tuberculosis,
      and isoniazid preventive therapy among persons with HIV, as well as tuberculosis
      control in the general population, are required to address these issues.

PMID- 24937805
TI  - Immune responses and protective efficacy of recombinant outer membrane protein R
      (rOmpR)-based vaccine of Aeromonas hydrophila with a modified adjuvant
      formulation in rohu (Labeo rohita).
AB  - Despite the importance and success of developing a candidate vaccine against
      Aeromonas hydrophila infection in fish, little is known about the molecular
      mechanisms of the vaccine-induced immunoprotection in Indian major carp, Labeo
      rohita, primarily due to lack of information on most of the immune related genes
      of the species. In this study, a novel candidate antigen recombinant outer
      membrane protein R (rOmpR) of A. hydrophila was evaluated as a vaccine candidate
      along with a modified adjuvant formulation. Protective efficacy of the rOmpR
      immunization was assessed in terms of survival against A. hydrophila challenge as
      well as modulation of immune response in vaccinated fish after 1, 3, 6, 12, 24,
      72 h and 10 days post-injection (using immune gene expression analysis) and 10,
      28, 56 and 140 days post-injection (serum immune parameter analysis). The
      generated immune response was compared with a formalin-killed A. hydrophila
      antigen preparation using mineral oil only and modified adjuvant alone. We report
      a variable up-regulation of the immune-related genes viz., lysozyme G, complement
      factor 4, immunoglobulin M, beta2-microglobulin, major histocompatibility complex
      I and II, and interleukin-1beta in anterior kidney and spleen tissues at early
      time points post-immunization in all the groups, when compared to the control
      fish. The vaccinated fish also showed an increase in serum natural hemolysin
      titer, lysozyme and myeloperoxidase activities, and antibody titer irrespective
      of vaccine formulations as compared to control fish on days 10, 28 and 56.
      However, the increase in the serum parameters was more pronounced on day 140 in
      rOmpR-modified adjuvant injected group, indicating the modulatory role of this
      new vaccine formulation. Upon challenge with live A. hydrophila on days 56 and
      140 post-immunization, significantly reduced percent mortality was noted in the
      group immunized with modified adjuvant based rOmpR vaccine formulation. Taken
      together, our results suggest that rOmpR along with modified adjuvant could
      potentially be used as a vaccine formulation to handle A. hydrophila infection on
      a long-term basis.

PMID- 24937806
TI  - Simultaneous multiplex PCR detection of seven cucurbit-infecting viruses.
AB  - Two multiplex polymerase chain reaction (PCR) systems using dual priming
      oligonucleotide (DPO) primers were developed for the simultaneous detection of
      seven cucurbit-infecting viruses. One system allows for the detection of papaya
      ringspot virus, watermelon mosaic virus, and zucchini yellow mosaic virus,
      whereas the other permits the detection of cucumber green mottle mosaic virus,
      cucumber fruit mottle mosaic virus, kyuri green mottle mosaic virus, and zucchini
      green mottle mosaic virus. Viral species-specific DPO primers developed in this
      study detected as little as 10 fg/MUl of viral RNA under monoplex conditions and
      10 pg/MUl of viral RNA under multiplex conditions. Multiplex PCR using the DPO
      primer sets was capable of amplifying viral genes at annealing temperatures
      ranging from 53  degrees C to 63  degrees C. Whereas the use of conventional
      primers gave rise to non-specific bands, the DPO primers detected target viral
      genes in the absence of non-specific amplification. When these DPO multiplex
      primer sets were applied to virus-infected cucurbit samples obtained in the
      field, multiple infection as well as single infection was accurately identified.
      This novel approach could also detect multiple viruses in infected seeds. The
      reliability of multiplex PCR systems using DPO primers for plant virus detection
      is discussed.

PMID- 24937807
TI  - Simultaneous determination of seventeen mycotoxins residues in Puerariae lobatae
      radix by liquid chromatography-tandem mass spectrometry.
AB  - This work reported an efficient and accurate liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method for simultaneous determination of seventeen
      mycotoxins in Puerariae lobatae radix, a frequently used traditional Chinese
      medicine (TCM). The effects of four different clean-up methods, including TC
      M160, TC-T220, Mycosep 227, and QuEChERS method, on the recoveries of mycotoxins
      were investigated and compared. Finally, TC-M160 was chosen for better recovery
      and repeatability for mycotoxins analysis. The analytes were separated on an
      Agilent ZORBAX SB C18 column (4.6mm*250mm, 5MUm particle size), and eluted with a
      mobile phase consisting of (A) water containing 0.1% formic acid and (B)
      acetonitrile containing 0.1% formic acid at a flow rate of 0.6mL/min. The
      separated compounds were detected by a triple quadrupole mass spectrometer
      operating in positive electrospray ionization with multiple reaction monitoring
      (MRM) mode. The results of method validation accorded with the requirement of
      analytical method for mycotoxins in COMMISSION REGULATION (EC) No 401/2006. The
      developed method was successfully applied for determination of mycotoxins in
      seventeen batches of Puerariae lobatae radix collected from different provinces
      of China. Three batches of them were found with contamination of mycotoxins AFB1
      at (0.751+/-0.176)MUg/kg, T-2 at (1.10+/-0.01)MUg/kg, and T-2 at (0.853+/
      0.044)MUg/kg, respectively. The results demonstrated that the proposed method was
      suitable for monitoring mycotoxins residues in Puerariae lobatae radix. 

PMID- 24937808
TI  - Comparative HPLC enantioseparation on substituted phenylcarbamoylated
      cyclodextrin chiral stationary phases and mobile phase effects.
AB  - Two new cyclodextrin-derived chiral stationary phases with multiple urea linkages
      were prepared through the Staudinger reactions between aminopropyl silica gel and
      cyclodextrin derivatives, namely, heptakis(6-azido-6-deoxy-2,3-di-O-3,5
      dimethylphenylcarbamoylated)-beta-cyclodextrin and heptakis(6-azido-6-deoxy-2,3
      di-O-3,5-dichlorophenylcarbamoylated)-beta-cyclodextrin, respectively. HPLC
      separation behaviors toward 46 chiral analytes have been investigated under
      multimodal elution. They exhibited good separation performances for these
      analytes and also showed some complimentary enantioselectivity to each other, due
      to different electron-donating (methyl)/withdrawing (chlorine) groups in the
      phenylcarbamate moieties. Among these analytes, aromatic alcohols and N-(2,4
      dinitrophenyl)-derived carboxylic acids were better resolved on the pi-basic
      chiral stationary phase than the pi-acidic. The proton pump inhibitors, the 5
      hydroxytryptamine receptor antagonists, and the analytes with carbonyl groups
      easily formed stereoselective interactions with the pi-acidic chiral stationary
      phase, further leading to better enantioseparation. Elution order reversal for
      palonosetron and N-(2,4-dinitrophenyl) glutamine was observed in three chiral
      stationary phases, probably induced by the difference of phenylcarbamate groups.
      Moreover, mobile phase effects on retention behaviors of analytes have been
      studied in detail. 

PMID- 24937809
TI  - A validated LC-MS/MS method for the rapid quantification of vilazodone in rat
      plasma: application to a pharmacokinetic study.
AB  - A rapid and sensitive LC-MS/MS method was developed for the quantification of
      vilazodone in rat plasma using escitalopram as internal standard. After extracted
      with organic solvent, post-treatment samples were chromatographed on an Agela C18
      column. An isocratic mobile phase of acetonitrile: 5mM ammonium acetate: formic
      acid (35:65:0.1, v/v/v) was applied at a flow rate of 0.25mL/min. Detection was
      performed using multiple reaction-monitoring (MRM) modes at m/z 442.4->155.3 for
      vilazodone and m/z 325.1->109.0 for escitalopram. The method was linear in the
      concentration range of 1.0-100ng/mL with a correlation coefficient >=0.993. The
      intra- and inter-assay precision (%RSD) values were within 13.4%, and intra- and
      inter-day accuracy (%RE) ranged from -9.8 to 6.9%. The total analysis time was
      2.2min. The LC-MS/MS method was fully validated for its sensitivity, selectivity,
      stability, matrix effect and recovery. The data indicated that the developed
      method was rapid, specific and sensitive. This method was further and
      successfully applied in the pharmacokinetics study of vilazodone in rat. 

PMID- 24937810
TI  - Integrating asthma hazard characterization methods for consumer products.
AB  - Despite extensive study, definitive conclusions regarding the relationship
      between asthma and consumer products remain elusive. Uncertainties reflect the
      multi-faceted nature of asthma (i.e., contributions of immunologic and non
      immunologic mechanisms). Many substances used in consumer products are associated
      with occupational asthma or asthma-like syndromes. However, risk assessment
      methods do not adequately predict the potential for consumer product exposures to
      trigger asthma and related syndromes under lower-level end-user conditions. A
      decision tree system is required to characterize asthma and respiratory-related
      hazards associated with consumer products. A system can be built to incorporate
      the best features of existing guidance, frameworks, and models using a weight-of
      evidence (WoE) approach. With this goal in mind, we have evaluated chemical
      hazard characterization methods for asthma and asthma-like responses. Despite the
      wealth of information available, current hazard characterization methods do not
      definitively identify whether a particular ingredient will cause or exacerbate
      asthma, asthma-like responses, or sensitization of the respiratory tract at lower
      levels associated with consumer product use. Effective use of hierarchical lines
      of evidence relies on consideration of the relevance and potency of assays,
      organization of assays by mode of action, and better assay validation. It is
      anticipated that the analysis of existing methods will support the development of
      a refined WoE approach. 

PMID- 24937811
TI  - Leprosy: a review of laboratory and therapeutic aspects--part 2.
AB  - Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M.
      leprae). It is endemic in many regions of the world and a public health problem
      in Brazil. Additionally, it presents a wide spectrum of clinical manifestations,
      which are dependent on the interaction between M. leprae and host, and are
      related to the degree of immunity to the bacillus. The diagnosis of this disease
      is a clinical one. However, in some situations laboratory exams are necessary to
      confirm the diagnosis of leprosy or classify its clinical form. This article aims
      to update dermatologists on leprosy, through a review of complementary laboratory
      techniques that can be employed for the diagnosis of leprosy, including Mitsuda
      intradermal reaction, skin smear microscopy, histopathology, serology,
      immunohistochemistry, polymerase chain reaction, imaging tests, electromyography,
      and blood tests. It also aims to explain standard multidrug therapy regimens, the
      treatment of reactions and resistant cases, immunotherapy with bacillus Calmette
      Guerin (BCG) vaccine and chemoprophylaxis. 

PMID- 24937813
TI  - Angiogenic effects of cryosurgery with liquid nitrogen on the normal skin of
      rats, through morphometric study.
AB  - BACKGROUND: Cryosurgery is an efficient therapeutic technique used to treat
      benign and malignant cutaneous diseases. The primary active mechanism of
      cryosurgery is related to vascular effects on treated tissue. After a
      cryosurgical procedure, exuberant granulation tissue is formed at the injection
      site, probably as a result of angiogenic stimulation of the cryogen and
      inflammatory response, particularly in endothelial cells. OBJECTIVE: To evaluate
      the angiogenic effects of freezing, as part of the phenomenon of healing rat skin
      subjected to previous injury. METHODS: Two incisions were made in each of the
      twenty rats, which were divided randomly into two groups of ten. After 3 days,
      cryosurgery with liquid nitrogen was performed in one of incisions. The rats'
      samples were then collected, cut and stained to conduct histopathological
      examination, to assess the local angiogenesis in differing moments and
      situations. RESULTS: It was possible to demonstrate that cryosurgery, in spite of
      promoting cell death and accentuated local inflammation soon after its
      application, induces quicker cell proliferation in the affected tissue and
      maintenance of this rate in a second phase, than in tissue healing without this
      procedure. CONCLUSIONS: These findings, together with the knowledge that there is
      a direct relationship between mononuclear cells and neovascularization (the
      development of a rich system of new vessels in injury caused by cold), suggest
      that cryosurgery possesses angiogenic stimulus, even though complete healing
      takes longer to occur. The significance level for statistical tests was 5%
      (p<0,05).

PMID- 24937812
TI  - Phenotypic, molecular and antimicrobial susceptibility assessment in isolates
      from chronic ulcers of cured leprosy patients: a case study in Southern Brazil.
AB  - BACKGROUND: One of the most stigmatizing physical sequelae of leprosy in cured
      patients is the development of chronic lower extremity ulcers. The bacterial
      diversity present in ulcers is considered one of the factors that can delay the
      healing process, as well as serve as a focus for severe secondary infections.
      OBJECTIVE: To identify the microbiota and antimicrobial resistance profile of
      bacteria isolated from skin ulcers in patients cured of leprosy. METHODS: After
      obtaining informed consent, material was collected from ulcers of 16 patients
      treated at the Outpatient Public Health Dermatology Clinic of Rio Grande do Sul
      and Hospital Colonia Itapua. Samples were collected during dressing, and the
      material sent to the Microbiology Laboratory of the Federal University of Health
      Sciences of Porto Alegre for microbiological culture. Methicillin-resistant
      Staphylococcus aureus (MRSA) was characterized by two molecular methods,
      including detection of the mecA gene by PCR and SCCmecgene typing. RESULTS:
      Cultures revealed microorganisms in all ulcers: Gram-negative bacilli in 80%,
      Gram-positive cocci in 63%, and mixed microflora in 36%. Staphylococcus aureus
      and Pseudomonas aeruginosa were the most prevalent bacteria. Assessment of the
      antimicrobial resistance profile was notable for the presence of MRSA. Molecular
      analysis of this isolate revealed presence of the mecA gene contained in a type
      IV staphylococcal cassette chromosome mec (SCCmec). CONCLUSIONS: In patients with
      leprosy, laboratory culture of skin ulcers is essential for correct antibiotic
      selection and to control emerging pathogens, such as MRSA carrying SCCmec type
      IV.

PMID- 24937814
TI  - Factors that influence healing of chronic venous leg ulcers: a retrospective
      cohort.
AB  - BACKGROUND: Venous ulcers have a significant impact on patient quality of life,
      and constitute a worldwide public health problem. Treatment is complex, with high
      failure rates. OBJECTIVES: To identify clinical and therapeutic factors that
      influence healing of venous ulcers. METHODS: Retrospective cohort study of
      patients with venous ulcers. Ulcer area was measured at the first visit (T0) and
      after 6 months (T6) and 1 year (T12). A reduction in ulcer area of 50% or more at
      T6 and T12 was the outcome of interest, weighted by clinical, demographic and
      treatment aspects. RESULTS: Ninety-four patients were included (137 ulcers). A
      reduction in ulcer area of 50% or more was seen in 40.1% of patients (95%CI 31.9
      to 48.4%) at T6 and 49.6% (95%CI 41.2 to 58.1%) at T12. Complete healing occurred
      in 16.8% (95%CI 10.5 to 23.1%) at T6 and 27% (95%CI 19.5 to 39.5%) at T12. The
      lowest ulcer area reductions at T6 were associated with longstanding ulcer
      (RR=0.95; 95%CI 0.91 to 0.98), poor adherence to compression therapy (RR=4.04;
      95%CI 1.31 to 12.41), and infection episodes (RR=0.42; 95%CI 0.23 to 0.76). At
      T12, lower reductions were associated with longstanding ulcer (RR=0.95; 95%CI
      0.92 to 0.98), longer topical antibiotic use (RR=0.93; 95%CI 0.87 to 0.99), and
      systemic antibiotic use (RR=0.63; 95%CI 0.40 to 0.99). CONCLUSIONS: Longstanding
      ulcer, infection, poor adherence to compression therapy, and longer topical and
      systemic antibiotic use were independently correlated with worse healing rates.

PMID- 24937815
TI  - Hepatitis C and hepatitis B virus infections in the etiopathogenesis of
      pemphigus.
AB  - BACKGROUND: Previous studies have shown that some viral infections may be
      triggers for autoimmune diseases. The role of viral infections in the
      etiopathogenesis of pemphigus has also been investigated. OBJECTIVES: To
      investigate the relationship between pemphigus and the hepatitis B and C virus
      infections. METHODS: This retrospective study included 62 patients with pemphigus
      and 50 healthy controls of matching ages and genders. The control group included
      relatives who accompanied the orthopedic patients to the hospital but had no
      history of systemic and/or autoimmune diseases. RESULTS: The group of patients
      with pemphigus was composed of 43 (69.3%) females and 19 (29.7%) males, and the
      mean age was 48.08 +/- 15.38. The hepatitis C virus antibody was negative in all
      of the patients. Hepatitis B surface antigen (HBsAg), hepatitis B surface
      antibody (HBsAb), or both, were studied in 44 of the 62 patients. Two (4.3%) of
      these patients were positive for HBsAg and found to have HBV infection. Fourteen
      of them were HBsAb positive. Two (4%) of the 50 control subjects showed hepatitis
      C virus antibody positivity, while only 1 (2%) patient with pemphigus displayed
      HBsAg positivity. There was no statistically significant difference between the
      two groups for hepatitis B and C virus infections. CONCLUSIONS: This study does
      not support an association between pemphigus and hepatitis B and/or C virus
      infections.

PMID- 24937816
TI  - Acne vulgaris: prevalence and clinical forms in adolescents from Sao Paulo,
      Brazil.
AB  - BACKGROUND: Acne is a common disease in adolescents, but there are no
      epidemiological data for acne in Brazil. OBJECTIVES: To estimate the prevalence
      and degree of acne in adolescents from Sao Paulo and study socio-demographic
      factors, family history and lifestyle, associated with the disease. METHODS:
      Cross-sectional study with 452 adolescents aged between 10 and 17 (mean=13.3
      years), students from elementary and high school, examined by 3 independent
      evaluators. RESULTS: 62.4% were female, 85.8% white and 6.4% were aged 14. The
      prevalence was 96.0% and increased with age--all students over 14 had acne. The
      most prevalent form of acne was comedonal (61.1%), followed by mild (30.6%) and
      moderate (7.6%) papular-pustular, which affected mostly the face (97.5%). About
      half of the adolescents reported family history for acne in mother or father, and
      20.6% reported previous treatment for acne. There was a higher chance of
      presenting non-comedonal acne with increased age (p<0.001). DISCUSSION: The
      prevalence of acne in adolescents varies widely due to the clinical features and
      diagnostic methods used. Adolescents whose brothers/sisters had acne (OR=1.7
      p=0.027) and those over 13 (OR=8.3-p<0.001), were more likely to have non
      comedonal acne. CONCLUSION: This study showed high prevalence of acne in
      adolescents from Sao Paulo, predominantly the comedonal form on the face, with a
      higher chance of presenting non-comedonal acne with increased age.

PMID- 24937817
TI  - Anti-TNFalpha therapy in the management of psoriasis: experience of a state
      referral center.
AB  - BACKGROUND: Psoriasis is a chronic immune-mediated disease, characterized by
      increased levels of TNFalpha. Anti-TNFalpha agents have revolutionized the
      treatment of severe psoriasis by targeting an important molecule involved in its
      pathogenesis. OBJECTIVES: We report the experience of a state referral center
      that uses anti-TNFalpha agents for psoriasis. METHODS: We conducted a
      retrospective case series. Seventy-four out of 120 patients met the inclusion
      criteria. Clinical and laboratory data was analyzed using the chi-squared,
      Wicoxon and McNemar's tests. Associations were considered statistically
      significant when p-value<0.05. RESULTS: Forty-one subjects (55.40%) were male,
      with a mean age of 47.69 +/- 14.99 years. Median disease duration and pre
      treatment PASI were 14.0 months (IQR 9.0-20.0), and 13.55 points (IQR 8.5-20.32).
      Sixty patients (81.10%) had arthropathic psoriasis. Forty-six subjects (62.20%)
      had comorbidities; the most frequent was dyslipidemia (25.70%). In 55.40% of
      patients, insufficient response to conventional therapies was the principal
      indication for using anti-TNFalpha drugs. Clinical improvement occurred in 93.20%
      of cases, and the post-treatment PASI median was 0.0 points (IQR 0.0-0.0).
      Adverse effects occurred in 6.80% of patients. Infections and elevation of
      transaminases occurred in 28.40% and 8.10% of cases, respectively. CONCLUSION:
      Post-treatment reduction in PASI was satisfactory and the occurrence of adverse
      effects was minor, mostly mild infusion effects and local reactions at drug
      administration sites.

PMID- 24937818
TI  - Cutaneous melanoma in the State of Sao Paulo: a spatial approach.
AB  - BACKGROUND: Cutaneous melanoma is a skin cancer with low incidence but high
      mortality rates. Several factors are associated with increased risk of melanoma,
      such as excessive sun exposure, fair skin, and family history, among others.
      Little is known about the spatial distribution of this cancer in Brazil.
      OBJECTIVE: To identify, through the use of geostatistical tools, spatial clusters
      of municipalities in the state of Sao Paulo based on their incidence of cutaneous
      melanoma. METHODS: This was an ecological and exploratory study of data on new
      cases obtained from Fundacao Oncocentro for the period 1 January 2006-31 December
      2011. Cases were separated by gender and rates per 100,000 inhabitants were
      calculated and used to compile thematic maps, Moran maps and kernel maps, using
      TerraView software. RESULTS: There were 3,172 new cases of cutaneous melanoma in
      the study period. High rates were identified in the North, Northwest, Southwest,
      and Southeast regions of Sao Paulo state. Global Moran's I values were
      statistically significant (p<0.05) at 0.12, 0.08, and 0.16, respectively, for
      males, females, and all cases. Areas such as the Southeast, North, and Northwest
      of Sao Paulo were identified as being of high priority for intervention.
      CONCLUSION: Spatial clusters of municipalities with high incidence rates of
      cutaneous melanoma in the state of Sao Paulo were identified. These data can
      serve as an important input for public health agencies.

PMID- 24937819
TI  - Herpes simplex virus: isolation, cytopathological characterization and antiviral
      sensitivity.
AB  - BACKGROUND: Herpes simplex virus (HSV) infection is an endemic disease and it is
      estimated that 6095% of the adult population are infected with symptoms that are
      usually self-limiting, though they can be serious, extensive and prolonged in
      immunocompromised individuals, highlighted by the emergence of drug-resistant
      strains. The study of the wild-type HSV strains based on the cytopathogenic
      features and its antiviral sensitivity are important in the establishment of an
      antivirogram for controlling the infection. OBJECTIVE: This study sought to
      isolate and examine the cytopathological characteristics of circulating strains
      of the Herpes simplex virus, from clinical specimens and their sensitivity to
      commercially available antiherpesvirus drugs, acyclovir, phosphonophormic acid
      and trifluridine. METHODS: Herpes simplex virus isolation, cytopathological
      features and antiviral sensitivity assays were performed in cell culture by
      tissue culture infectious dose or plaque forming unit assay. RESULTS: From twenty
      two clinical specimens, we isolated and adapted nine strains. Overall, the
      cytopathic effect was detected 24 h post-infection (p.i.) and the presence of
      syncytia was remarkable 48 h p.i., observed after cell staining. Out of eight
      isolates, four developed plaques of varying sizes. All the isolates were
      sensitive to acyclovir, phosphonophormic and trifluridine, with the percentage of
      virus inhibition (%VI) ranging from 49.7-100%. CONCLUSIONS: The methodology for
      HSV isolation and characterization is a straightforward approach, but the drug
      sensitivity test, regarded as being of great practical importance, needs to be
      better understood.

PMID- 24937820
TI  - Teaching of leprosy: current challenges.
AB  - In the context of declining leprosy endemicity worldwide, keeping the interest in
      knowledge and expertise in leprosy alive has been a matter of concern.
      Approaching the problem only in primary care, without the proper integration with
      other levels of care in the health system fails to account for the complexity of
      the disease. Training professionals to work at different levels of health care is
      a current challenge. The objective of this review was to look for experiences
      related to the teaching of leprosy both in undergraduate courses in the field of
      health sciences and in training programs for professionals who work in patient
      care. We highlight the role of the dermatologist in the management of control
      programs, diagnosis and treatment of the disease, as well as in the continuous
      education of other health professionals. 

PMID- 24937823
TI  - Abscess resulting from Mycobacterium kansasii in the left thigh of AIDS patient.
AB  - A case of abscess resulting from Mycobacterium kansasii, in the left thigh of a
      53-year-old woman infected with the Human Immunodeficiency virus, is reported.
      Curiously, there was no pulmonary or systemic involvement as is usual with these
      Mycobacterium infections. The patient had CD4 T lymphocyte count of 257 cells/uL
      and a viral load of 60,154 copies. Despite presenting a relatively preserved
      immunity, the patient also presented Criptococcic meningoencephalitis and
      Esophageal candidiasis. The patient responded satisfactorily to treatment for
      infections and after 51 days was discharged. 

PMID- 24937822
TI  - Variants of dermatofibroma--a histopathological study.
AB  - Several variants of dermatofibroma have been described. They are essentially
      distinguished by their clinical and histopathological features. To review the
      mainfeaturesof these variants, a retrospective study of skin biopsies and tissue
      excisions of dermatofibromasperformed in the dermatology and venereology service
      at the Hospital Garcia de Orta between May 2007 and April 2012 was carried out.
      During that period, 192 dermatofibromas were diagnosed in 181 patients, the
      lesions being more common in women. Median age of the study population was 48
      years. The most common lesion site was the limbs (74% of patients). The
      histopathological types found were common fibrous histiocytoma (80%) and the
      aneurysmal (5.7%),hemosiderotic (5.7%), epithelioid (2.6%), cellular (2.1%),
      lipidized (2.1%), atrophic (1.0) and clear cell (0.5%) variants. Based on these
      findings, this review focuses on the clinical and histological features of the
      various variants of dermatofibroma in terms of their clinical presentation,
      distinct histopathological features, differential diagnosis and prognosis. 

PMID- 24937824
TI  - Verrucous lepromatous leprosy: a rare form of presentation--report on two cases.
AB  - Leprosy skin lesions are described as hypochromic or erythematous macules, pale
      erythematous or reddish-brown plaques, papules, nodules, and diffuse cutaneous
      infiltration, depending on the clinical form of the disease. They may be
      accompanied by hypo or anesthesia, alopecia, and hypo or anhidrosis. Verrucous
      lesions are now quite uncommon in leprosy. The literature is sparse, with only 25
      reported cases of this association, especially in the lepromatous pole of the
      disease. This work is a report on two cases of lepromatous leprosy of long
      evolution, coursing with vegetant verrucous lesions. 

PMID- 24937825
TI  - Incontinentia pigmenti or Bloch-Sulzberger syndrome: a rare X-linked
      genodermatosis.
AB  - Incontinentia pigmenti is a rare X-linked genodermatosis that affects mainly
      female neonates. The first manifestation occurs in the early neonatal period and
      progresses through four stages: vesicular, verruciform, hyperpigmented and
      hypopigmented. Clinical features also manifest themselves through changes in the
      teeth, eyes, hair, central nervous system, bone structures, skeletal musculature
      and immune system. The authors report the case of a patient with cutaneous
      lesions and histological findings that are compatible with the vesicular stage,
      emphasizing the importance of early diagnosis and appropriate therapeutic
      management. 

PMID- 24937821
TI  - Vitiligo--part 1.
AB  - Vitiligo is a chronic stigmatizing disease, already known for millennia, which
      mainly affects melanocytes from epidermis basal layer, leading to the development
      of hypochromic and achromic patches. Its estimated prevalence is 0.5% worldwide.
      The involvement of genetic factors controlling susceptibility to vitiligo has
      been studied over the last decades, and results of previous studies present
      vitiligo as a complex, multifactorial and polygenic disease. In this context, a
      few genes, including DDR1, XBP1 and NLRP1 have been consistently and functionally
      associated with the disease. Notwithstanding, environmental factors that
      precipitate or maintain the disease are yet to be described. The pathogenesis of
      vitiligo has not been totally clarified until now and many theories have been
      proposed. Of these, the autoimmune hypothesis is now the most cited and studied
      among experts. Dysfunction in metabolic pathways, which could lead to production
      of toxic metabolites causing damage to melanocytes, has also been investigated.
      Melanocytes adhesion deficit in patients with vitiligo is mainly speculated by
      the appearance of Koebner phenomenon, recently, new genes and proteins involved
      in this deficit have been found. 

PMID- 24937826
TI  - Unusual manifestation of the yellow nail syndrome--case report.
AB  - The yellow nail syndrome is a rare disorder characterized by the classic triad of
      yellow and dystrophic nails, lymphedema and pleural effusion. We report in this
      paper a case of yellow nail syndrome, presenting the classic triad of the
      disease, associated with an unusual lymph accumulation in the abdomen region. 

PMID- 24937827
TI  - Surgical options for treatment of lip and perioral tumors: report of 5 cases.
AB  - Basal cell and squamous cell carcinomas are the main neoplasms of lip and
      perioral location. We describe different techniques of successful surgical
      reconstruction, including flaps or simple incision and suture. Using the latter
      technique satisfactory results were demonstrated, although the incision made
      removed more than a third of the lip, contrary to the literature. Our goal is to
      emphasize that the common sense and experience of the surgeon should prevail in
      the choice of reconstructive method. Moreover, even if the priority is complete
      excision of the lesion, we cannot ignore the aesthetic and functional recovery
      objective. 

PMID- 24937828
TI  - Pityriasis Rubra Pilar and hypothyroidism.
AB  - Pityriasis Rubra Pilaris (PRP) is a chronic and rare papulosquamous disorder.
      Treatment of Pityriasis Rubra Pilaris is based on empiric evidence because of
      several doubts regarding its etiology and also because of its relative rarity,
      making randomized studies difficult to perform. Some factors suggest that the
      metabolism of vitamin A is involved in pathogenesis. We report a case of
      Pityriasis Rubra Pilaris associated with autoimmune hypothyroidism which
      presented rapid and complete response after thyroid hormone replacement, without
      any association with other systemic treatment. In literature there are only three
      other reports of significant improvement of the lesions after hormonal
      correction. Deficiency of thyroid hormone inhibits the conversion of carotene
      into vitamin A, which would be responsible for the occurrence of Pityriasis Rubra
      Pilaris in this patient. 

PMID- 24937829
TI  - Primary cutaneous Ewing sarcoma--case report.
AB  - Ewing sarcoma is a primitive neuroectodermal tumor rarely occurs in the skin and
      sobcutaneous tissues. Generally Ewing's sarcoma is a primary bone tumor, but when
      present in soft tissues it characterizes an extremely uncommon clinical picture.
      It usually involves the deep subcutaneous tissue or muscles, and more rarely
      occurs like a primary skin cancer. Most patients are white, women, and in the
      second decade of life. The clinical features are a superficial mass, in average
      measuring 2-3 cm, of soft consistency, freely mobile and sometimes painful. The
      more affected locations are upper and lower extremities, trunk, head, neck or
      multiple lesions. The presence of metastases is very rare. 

PMID- 24937830
TI  - Clouston syndrome associated with eccrine syringofibroadenoma.
AB  - Eccrine syringofibroadenoma is a rare benign neoplasia derived from acrosyryngium
      cells of the eccrine sudoriferous glands. It affects the extremities of elderly
      individuals as solitary tumors, or may also present as multiple lesions. There
      are controversies about the pathogenesis and differentiation of the tumor.
      Eccrine syringofibroadenoma has been associated with subjacent conditions, such
      as for example, hypohidrotic ectodermic dysplasias. The authors describe a case
      report of a patient with Clouston Syndrome, who presented papules and nodules in
      extremities, clinically and histologically compatible with eccrine
      syringofibroadenoma. There are only three cases described in the literature,
      associated with Clouston Syndrome, and this is the fourth case. 

PMID- 24937831
TI  - Confluent and reticulate papillomatosis of Gougerot-Carteaud and obesity:
      dermoscopic findings.
AB  - Confluent and reticulated papillomatosis of Gougerot and Carteaud is a dermatosis
      that despite showing characteristic clinical signs is often poorly recognized and
      diagnosed. The authors present a case with extensive skin involvement, discuss
      its association with obesity and describe dermoscopic findings making the
      histopathological correlation. 

PMID- 24937832
TI  - Case report: Dermoscopic and histological aspects of skin graft and perigraft
      hyperpigmentation in acral location.
AB  - Little is known about the use of dermoscopy in skin grafting. We describe the
      case of a patient with skin grafting and surrounding pigmentation on acral
      region. The dermoscopic findings were similar to those of benign acral lesions
      (lattice-like pattern) and reactive pigmentations (fine striae). Histopathology
      revealed pigment leakage and increased number of melanocytes. It is believed that
      this phenomenon occurred as the result of an inflammatory stimulus.

PMID- 24937833
TI  - Dermoscopy applied to pediculosis corporis diagnosis.
AB  - We report the case of a 47-year-old homeless male with a massive infestation of
      Pediculus humanus corporis on his entire body. Dermoscopy helped to diagnose
      pediculosis by showing the involvement of scalp, beard and the genital region in
      this disease. 

PMID- 24937834
TI  - History of leprosy in Rio de Janeiro.
AB  - The record of the first cases of leprosy in Rio de Janeiro dates from the
      seventeenth century. The first local host of leprosy patients was created from
      1741, and the first colonies hospitals were built in the early twentieth century,
      in order to avoid contagion of the population. The first structures dedicated to
      research also date from this time: the Leprosy International Institute, the
      Leprology Institute, and the Leprosy Laboratory of the Oswaldo Cruz Foundation,
      where the most prestigious leprologists of Rio de Janeiro worked. Currently,
      investigations are focused on the Oswaldo Cruz Foundation; additionally, leprosy
      patients are treated at municipal health centers and state hospitals, and former
      colony hospitals only accept patients with severe disabilities. 

PMID- 24937835
TI  - Case for diagnosis.
AB  - We report the case of an 11-year-old male patient with a histopathological and
      immunohistochemical diagnosis of dermatofibroma with an atypical clinical
      presentation on the right forearm. Although dermatofibroma is considered a benign
      skin tumor, some of its differential diagnoses, such as dermatofibrosarcoma
      protuberans and malignant fibrous histiocytoma, are truly aggressive. Lesions
      with atypical clinical aspects and topology associated with specific
      histopathological variants are some of the criteria for complete tumor excision. 

PMID- 24937836
TI  - Case for diagnosis.
AB  - Degos disease, also known as malignant atrophic papulosis, is a rare occlusive
      vasculopathy of unknown etiology characterized by infarcts in the dermis,
      gastrointestinal tract, central nervous system, and other organs. It is
      characterized by papules, which become umbilicated and evolve with a depressed
      porcelain-white central area, with an erythematous halo with telangiectasias.
      Histological findings include wedge-shaped dermoepidermal necrosis and blood
      vessel thrombosis. Approximately 50-60% of patients with systemic symptoms die
      within 2-3 years, most due to gastrointestinal perforation. We report a typical
      case, with lethal outcome, in a 45-year-old woman. 

PMID- 24937837
TI  - Case for diagnosis.
AB  - Granular cell tumour is a rare tumour of neural origin usually located on the
      face and the neck. The biological behaviour is usually benign. However, certain
      clinical and histopathological features should alert physicians to a malignant
      behaviour. This case report describes the occurrence of a granular cell tumour in
      the inguinal area that resembled a malignant tumour. The histopathological study
      revealed typical features of granular cell tumour and an extension study
      confirmed the absence of metastasis. This case highlights the importance of
      considering this disorder in the differential diagnosis of ulcerated nodules and
      of managing atypical granular cell tumor appropriately. 

PMID- 24937838
TI  - Syndrome in question.
AB  - A 48-year-old male patient with chronic alcoholism presented with a soft, bulky,
      asymptomatic, and slow-growing mass in the posterior region of the neck, as well
      as nodules in the deltoid region and posterior triangle of the
      sternocleidomastoid muscle. Needle aspiration confirmed the diagnosis of lipoma.
      Multiple symmetric lipomatosis (Madelung's disease) is a rare proliferation of
      adipocytes, of unknown etiology, most common in middle-aged men and mainly
      associated with alcoholism. It predominantly affects the neck and upper trunk,
      causing compressive symptoms or a imparting a pseudoathletic appearance. Surgical
      resection or liposuction is the most effective treatment, despite frequent
      recurrence. 

PMID- 24937839
TI  - Increasing trend of sensitization to
      Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI).
AB  - Recent reports have shown increased sensitization to
      Methylchloroisothiazolinone/methylisothiazolinone. We report a retrospective
      study conducted at the Hospital das Clinicas--UFMG, based on the results of patch
      tests with the Brazilian standard series, performed on referred patients. The
      positive results in 359 patients from November 2009 to October 2012 were analyzed
      and compared with the previous data collected from March 2006 to October 2009
      (447 patients). The data showed 11.14% sensitization to
      Methylchloroisothiazolinone/ methylisothiazolinone during 2009-2012, contrasting
      with the previous period (3.35%). A positive association was found between its
      positivity and the period of 2009-2012.

PMID- 24937840
TI  - Skin diseases reported by workers from UNESP campus at Rubiao Jr, Botucatu-SP
      (Brazil).
AB  - There are few populational studies to estimate the dimension of dermatological
      diseases. We performed a survey with 515 employees from UNESP campus, Botucatu
      (SP), exploring demographic data, medical appointments and dermatological
      diagnoses. Additionally, we induced questions about prevalent diseases.
      Appointments to the dermatologist were reported by 77% of subjects. The main
      dermatoses spontaneously reported were mycoses, allergies, nevi and viral warts.
      There were association of juvenile acne and males (OR=2.3), melasma and females
      (OR=8.0), and onychomycosis with older age (OR=1.05). Surveys are important to
      know the demand for dermatology care, besides directing formulation of public
      health policy and medical education. 

PMID- 24937841
TI  - Cutaneous ulcer in an immunosuppressed patient with adult onset Still's disease:
      primary cutaneous histoplasmosis?
AB  - Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum.Primary
      infection occurs through inhalation of spores from the air. Immunocompetent
      individuals are usually asymptomatic, but may develop pulmonary disease.
      Immunocompromised patients tend to present systemic histoplasmosis with cutaneous
      lesions occurring by secondary invasion. In this case report, we describe a
      probable primary cutaneous histoplasmosis (PCH) in a patient with adult onset
      Still's disease under immunosuppression. 

PMID- 24937843
TI  - Cardiac biomarker testing in the clinical laboratory: where do we stand? General
      overview of the methodology with special emphasis on natriuretic peptides.
AB  - Diagnosis of heart failure (HF) is not based on a single test, but on a
      combination of history, physical examination and appropriate investigations. For
      these reasons, the accuracy of diagnosis by clinical means alone is often
      inadequate, especially in the early, asymptomatic stages of the HF. Thus, there
      is an increasing interest in the development of new cardiovascular biomarkers
      and, consequently, a great number of laboratory tests have recently been proposed
      for their assay. The aim of this article is to provide a general overview on the
      biomarkers, recommended by international guidelines, for the diagnosis, risk
      stratification, and follow-up of patients with HF. Cardiac natriuretic peptides
      and in particular the B-type related peptides, which are considered to be the
      first line biomarker for HF by international guidelines, will be discussed with
      special emphasis. 

PMID- 24937844
TI  - A sight saver: cataract surgery.

PMID- 24937846
TI  - Fixes for faulty heart valves: which techniques work best?

PMID- 24937845
TI  - Understanding Lewy body dementia.

PMID- 24937847
TI  - Getting a grip on severe hand osteoarthritis.

PMID- 24937848
TI  - 10 tips for safe oxygen use and storage.

PMID- 24937849
TI  - How long is a cold contagious?  Is there any way to prevent transmitting a cold
      to another person?

PMID- 24937850
TI  - Are drugs that have passed their expiration dates OK to use, or should they be
      discarded?

PMID- 24937851
TI  - Another pill for breast cancer prevention.

PMID- 24937852
TI  - Don't take knee pain lying down.

PMID- 24937853
TI  - A one-two punch against prostate cancer.

PMID- 24937854
TI  - Mind the bed-rail gap.

PMID- 24937855
TI  - Pulmonary Cryptococcosis.

PMID- 24937856
TI  - Dr. Steven A. Rasmussen: from Brown alum to department chair.

PMID- 24937857
TI  - Words expressing finality.

PMID- 24937858
TI  - Paraphilia.

PMID- 24937859
TI  - Paget's disease of the breast.

PMID- 24937860
TI  - Jay publishes research on new OA prevention treatment.

PMID- 24937861
TI  - Rhode Island Hospital opens COBRE center for stem cell biology.

PMID- 24937862
TI  - Bradley researchers find age-related changes in how autism affects the brain.

PMID- 24937863
TI  - Differential expression of bithorax complex genes in the absence of the extra sex
      combs and trithorax genes.
AB  - Each body segment of Drosophila follows a unique developmental pathway,
      controlled by the selective expression of homoeotic genes such as Sex combs
      reduced (Scr)and the bithorax complex (BX-C). Little is known about the
      regulation of these genes, though several potential activators or repressers have
      been described. For instance, absence of the extra sex combs (esc) gene product
      apparently causes adventitious expression of all the BX-C genes in most or all
      larval body segments. Absence of the trithorax (trx) gene appears to prevent Scr
      and BX-C expression but only in adult cells; differentiation of the larval
      segments is only slightly affected. I show here that the correct segmental
      differentiation of the larva does not require maternally deposited trx+ product,
      but that the esc mutant phenotype is suppressed by the removal of the trx gene,
      which implies that the BX-C can be differentially expressed in the absence of
      both the trx gene and the esc gene product.

PMID- 24937864
TI  - HIV therapy for treatment-experienced patients: multi-site study, led by Miriam's
      Tahsima could change treatment. strategy.

PMID- 24937865
TI  - Women & infants launches 'safe to sleep' campaign: saving infants from accidental
      crib deaths.

PMID- 24937866
TI  - Editorial: Psychiatry and conflict.

PMID- 24937867
TI  - Preventing infection from the misuse of vials.

PMID- 24937868
TI  - Ellenbogen speaks on head injuries in youth, the NFL, military: co-chair of the
      NFL Head, Neck and Spine Committee since 2010.

PMID- 24937869
TI  - In editorial, RIH's Dr. Ranney calls for research into gun violence.

PMID- 24937870
TI  - Alpert Medical School mints 113 new physicians.

PMID- 24937871
TI  - A tendency toward wordiness.

PMID- 24937872
TI  - Authors' reply.

PMID- 24937873
TI  - Authors' reply.

PMID- 24937874
TI  - Switch to the new peak flow reference equations for adults in India.

PMID- 24937875
TI  - Microalbuminuria: nature, importance, significance, and limitations.

PMID- 24937876
TI  - Multiple myeloma pathogenesis: blame it on the microenvironment.

PMID- 24937878
TI  - OBSTACLE hypoglycemia: Targeting a major hurdle in diabetes management!

PMID- 24937877
TI  - Acute kidney injury biomarkers: need to move from bench to bedside.

PMID- 24937879
TI  - Equine cyathostomins.
AB  - This collection of articles provides an in depth account of five presentations
      delivered during the Symposium on Equine Cyathostomins held at the 19th
      International Conference of the World Association for the Advancement of
      Veterinary Parasitology (WAAVP), New Orleans, Louisiana,10-14 August 2003. The
      symposium was organized and chaired by Ray M. Kaplan and Jacqui B. Matthews and
      focused on new developments in two major areas of current importance: the
      immunobiology of cyathostomin-horse interactions and anthelmintic resistance.

PMID- 24937880
TI  - Molecular systematics and diagnosis.
AB  - This collection of articles provides an account of six presentations delivered at
      the 19th International Conference of the World Association for the Advancement of
      Veterinary Parasitology(WAAVP) (held in New Orleans, Louisiana, USA, from 10 to
      14 August 2003) in a symposium session on Molecular Systematics and Diagnosis,
      organised and chaired by R.B. Gasser and D.S. Zarlenga. The focus was on recent
      advances in molecular tools for specific and genotypic identification,diagnosis,
      systematics and population genetics, with special emphasis on investigations of
      parasitic nematodes and protists.

PMID- 24937881
TI  - Novel approaches to control of parasites-a workshop.
AB  - With the advent of helminth parasite populations that have developed resistance
      to anthelmintics over the last decade or so, especially in small ruminants,
      sustainable productivity has been threatened. This workshop on novel approaches
      to control was held at the 19th International Conference of the World Association
      for the Advancement of Veterinary Parasitology (WAAVP) at New Orleans,LA, USA,
      during 10-14 August 2003. The workshop was organized and chaired by J.E. Miller
      and P.J. Waller. Novel or alternative approaches to control have been the focus
      of research (basic and applied) in many parts of the world. The objective of the
      workshop was to discuss where we have been and what direction(s) appears to be
      viable for both the short and long term future. In the long term, all represented
      regions at the workshop have promulgated programs where breeding for resistance
      may be the best approach as genes for resistance can be fixed in host
      populations. However,it does take many years to achieve results and the question
      of tradeoff concerning alteration of production traits needs further evaluation.
      Vaccination, especially against Haemonchus contortus,has been a thrust of
      laboratories in Scotland and Australia where natural "hidden gut" antigens have
      shown promise, but recombinant products have yet to be developed. In Europe,
      North and South America, Australia, South Africa and Asia, biocontrol using the
      nematode-trapping fungus Duddingtonia flagrans has been shown to be effective
      under experimental conditions, but some field evaluations have been
      disappointing. Most recently, the FAMACHA system was developed in South Africa.
      This system is directly and immediately applicable to all regions where H.
      contortus is a problem. Although not a new or novel approach, copper-oxide wire
      particles have been revived as a means to control H. contortus.Work being done in
      Europe, North and South America,South Africa and Australia have shown very
      encouraging results and can probably be considered the best short term approach
      available. However, caution needs to be considered in sheep to avoid potential
      copper toxicity problems. Work in New Zealand, Scotland and the US with forages
      and feeds containing condensed tannins have shown some limited control. Many
      laboratories have demonstrated that adequate and balanced nutrition programs are
      also important to maintain mechanisms that combat infections. Overall, no one
      approach alone is the answer. Approaches that are integrated, including "smart"
      use of anthelmintics, are necessary.

PMID- 24937882
TI  - Recent advances in heartworm disease.
AB  - This compilation of articles consists of four papers presented at the 19th
      International Conference of the World Association for the Advancement of
      Veterinary Parasitology (WAAVP) (held in New Orleans, LA, USA, on 10-14 August
      2003) in a symposium session titled " Recent Advances in Heartworm Disease,"
      organized and chaired by JohnW. McCall and Jorge Guerrero. The first
      paper(Guerrero) covered the American Heartworm Society's most recent revision of
      their guidelines for the diagnosis, prevention, and management of heartworm
      infection in dogs, based on new research and clinical experience, particularly in
      the areas of heartworm chemoprophylaxis, adulticide therapy,and serologic testing
      and retesting. The entire updated 2003 "Guidelines" are presented herein.One
      paper (McCall) reviewed the "soft-kill" adulticidal and "safety-net" (reach-back,
      retroactive,clinical prophylactic) activity of prolonged dosing of prophylactic
      doses of macrocyclic lactones,concluding that ivermectin is the most effective in
      this way, milbemycin oxime is the least effective,and the activity of injectable
      moxidectin and selamectin lies between that of ivermectin and milbemycin oxime.
      The two remaining papers provided an overview of the discovery,
      rediscovery,phylogeny, and biological association between Wolbachia endosymbionts
      and filarial nematodes(Genchi and co-authors) and compelling evidence that
      Wolbachia may play a major role in the immunopathogenesis of filarial diseases of
      man and animals (Kramer and co-authors).

PMID- 24937883
TI  - Management of myiasis: current status and future prospects.
AB  - The management of myiasis in livestock has been an example of the success of
      modern chemical approaches for parasite control, yet in some cases remains
      extremely intractable, requiring the development of novel strategies. In
      addition, the growing and urgent need to develop integrated strategies that
      enhance the sustainability of livestock production systems drives the search for
      new techniques [see Int. J. Parasitol. 29 (1999) 7].The following summary
      represents a synthesis of a symposium presented at the 19th International
      Conference of the World Association for the Advancement of Veterinary
      Parasitology, New Orleans,USA, 10-14 August 2003. The coverage began with a
      review of the need for more subtle economic analysis of the impact of myiasis
      based on the use of the sterile insect technique (SIT) for control of bovine
      hypodermosis in North America. This was followed by a review of the status of
      chemical control with particular emphasis on the macrocyclic lactones. The
      outcome of the use of these compounds in a regulated control program for
      eradication of bovine hypodermosis in EU was surveyed. Similarly, the success of
      the screwworm eradication program, using the sterile insect technique has shown
      how effective this approach can be given the appropriate target. Several aspects
      of the development of newer approaches were surveyed in discussion of newer
      chemical control products, development of vaccines, use of host genetics, use of
      predictive simulation modelling and trapping for monitoring and control and the
      development of new diagnostic approaches for occult infestations. Finally, use of
      the latest molecular tools for identification of larvae causing myiasis and their
      use for the identification of species coming from different and distant
      geographical areas to colonize regions where they have been eradicated was
      reviewed.

PMID- 24937884
TI  - Zoonotic protozoa in the marine environment: a  threat to aquatic mammals and
      public health.
AB  - This collection of abstracts provides an account of four presentations at the
      19th International Conference of the World Association for the Advancement of
      Veterinary Parasitology (WAAVP)(held in New Orleans, LA, USA from 10-14 August
      2003) in a symposium session on zoonotic protozoan parasites found in the marine
      environment and chaired by Ronald Fayer and David Lindsay.The focus was on three
      genera of parasites of veterinary and public health concern-Toxoplasma,Giardia,
      and Cryptosporidium with emphasis on their epidemiology in the marine
      environment.

PMID- 24937885
TI  - AAVP Symposium: new approaches  in the study of animal parasites.
AB  - The following three papers are a very small window onto the types of research
      being pursued by members of the American Association of Veterinary
      Parasitologists. They are related by the fact that newer areas in the biology of
      parasites and their hosts are discussed. The first paper by Dr. Tom Klei, gives a
      brief view of the interactions between host and parasite of the fascinating
      organism Wolbachia, a parasite of parasites. The second paper by Dr. Gloria
      Solano-Aguilar addresses the use of probiotics to alter the host-parasite
      interface and influence host resistance. The final paper by Dr. Lou Gasbarre
      outlines an example of integration of the genomics revolution into Veterinary
      Parasitology. While the subjects are diverse, they demonstrate the vitality of
      the AAVP.

PMID- 24937886
TI  - Assessing the burden of Taenia solium  cysticercosis and echinococcosis.
AB  - This collection of articles provides an account of the papers delivered at the
      19th International Conference of the World Association for the Advancement of
      Veterinary Parasitology (WAAVP)(held in New Orleans, LA, USA, from 10 to 14
      August 2003) in a symposium session on assessing the burden of Taenia solium
      cysticercosis and echinococcosis organised and chaired by A. Lee Willingham III
      from the WHO/FAO Collaborating Center for Research and Training on Emerging and
      other Parasitic Zoonoses in Denmark and Peter M. Schantz from the Parasitic
      Diseases Division of the US Centers for Disease Control and Prevention, USA. The
      focus was on the persistence of the zoonotic parasitic diseases cysticercosis,
      caused by the pork tapeworm T. solium, and echinococcosis,caused by species of
      the tapeworm Echinococcus, and why these diseases are given very little attention
      on the national and international agendas in spite of the availability of tools
      to detect, treat,control and prevent them when it is quite clear in most
      instances that they are clearly associated with and help perpetuate poverty. A
      major reason for this is that in many endemic areas the presence and impact of
      these diseases are not known due to the lack of investigation and information
      thus policymakers are not aware of their burden and benefits of their control.
      Documentation is also needed to help increase awareness of the international
      community and hopefully result in financial and technical support being made
      available. Thus, burden assessments of cysticercosis and echinococcosis provide
      an essential evidence base for securing political will and financial and
      technical support as well as providing a basis for cost-benefit analysis of
      prevention and control efforts. In order to make an appropriate and full burden
      assessment one must consider the health, agricultural, social and other impacts
      of these parasitic zoonoses comprehensively. During the symposium presentations
      were given concerning current ongoing initiatives to assess the burden of
      cysticercosis and echinococcosis and examples of the impact of these diseases in
      both developing and developed countries were provided. In addition, cost factors
      related to vaccines for these cestode diseases were discussed and the
      possibilities for technical and financial support from multilateral agencies for
      assessments and interventions presented.

PMID- 24937887
TI  - Intervet symposium: bovine neosporosis.
AB  - This article summarises the most relevant data of presentations delivered at the
      19th International Conference of the World Association for the Advancement of
      Veterinary Parasitology (WAAVP)held in New Orleans, LA, USA, from 10 to 14 August
      2003) in a symposium session on bovine neosporosis. The symposium was organised
      by Juan Munoz-Bielsa,Wicher Holland, Enzo Foccoliand Theo Schetters (chairman).
      The focus was on the present state of knowledge of the biology,
      epidemiology(presented by J.P. Dubey) and immunology of Neospora infection
      (presented by A. Adrianarivo),with special emphasis on the prospects of
      vaccination of cattle against Neospora-induced abortion (presentations of K.
      Frankena (Costa Rican trial) and C. Heuer (New Zealand trial)).

PMID- 24937888
TI  - TDA House of Delegates.

PMID- 24937889
TI  - Case of the month. Ectopic geographic tongue (erythema migrans).

PMID- 24937890
TI  - Cat of the month. Critically appraised topics. Dentists' awareness of posture in
      reducing pain in musculoskeletal disorder (MSD) UT CAT #2336.

PMID- 24937891
TI  - Unusual radiographic finding during routine periodontal maintenance: a case
      report.
AB  - This case report describes the presence of a radiopaque artifact appearing in
      multiple intraoral periapical and bitewing radiographs during routine periodontal
      maintenance, in an edentulous area with a history of a ridge preservation
      procedure. Clinical examination of the area showed a normal soft tissue
      appearance. Upon further investigation of the patient's recent past medical
      history, it was found that the artifact was due to the presence of a dermal
      filler (Radiesse--Merz Aesthetics, San Mateo, CA), which remained after a facial
      cosmetic procedure. This unusual finding is an indication that clinicians should
      consider facial cosmetic dermal fillers as part of the differential diagnosis
      when unusual radiopaque objects are found during routine dental radiographs.

PMID- 24937893
TI  - Informed refusal: a review.

PMID- 24937892
TI  - Digital dentistry and implant dentistry--a case study.
AB  - In the area of fixed prosthodontics, implants have evolved to become the gold
      standard in terms of longevity and esthetic outcome (1). As in all of dentistry,
      careful diagnosis and treatment planning is a must to achieve an optimum result.
      When evaluating the recipient site, one must determine if any type of defect
      (hard or soft tissue) exists which would require augmentation. The existing
      occlusion must also be evaluated to ensure the dentist is aware of possible
      prosthetic complications. In straightforward cases, such as those without the
      need for augmentation, the conventional timeline requires a waiting period of 3
      months following surgical placement to begin the restorative procedures.
      Factoring in the restorative time frame, the patient may wait up to approximately
      4 months for the final implant prosthesis. Various advancements in dentistry are
      changing the way dentists approach implant dentistry--from diagnosis and
      treatment planning to final restorations. This article illustrates these advances
      through a case study.

PMID- 24937894
TI  - Self-care, an ounce of prevention.

PMID- 24937895
TI  - School nurse health wellness: making it priority one.

PMID- 24937896
TI  - Health and wellness begin with school nurses.

PMID- 24937897
TI  - The role of school nurses in integrated pest management: protecting children from
      pests and pesticides.

PMID- 24937898
TI  - Healthy children learn better, and healthy school nurses make it happen!! Apps to
      inspire wellness.

PMID- 24937899
TI  - Wellness promotion: school nurses as models of health.
AB  - Students and staff of all ages look to school nurses as authorities on health and
      wellness. Health promotion and wellness education are school nursing practices
      that have the potential for continuous impact on students. School nurses have the
      critical responsibility of acknowledging their influences on the health behavior
      of others and are called to take ownership of the essential role of modeling
      wellness.

PMID- 24937900
TI  - Alliance for a healthier generation: resources and practices to support the
      school nurse role in building a healthier school environment.

PMID- 24937901
TI  - Nurses lead the way for "safe in the sun" play!
AB  - Skin cancer prevention is of great importance as it is the most common type of
      cancer in the United States. Much skin damage occurs early in life. Adolescents
      are a vulnerable population, as they strive to fit in with their peers, and they
      neglect sun safety habits. Since a substantial portion of adolescents' time is
      spent at school, school nurses are in an ideal position to develop and lead a sun
      safety action plan, using guidelines from the Centers for Disease Control and
      Prevention and evidence-based sun safety internet resources. It is hoped that
      incorporating a culture of skin health promotion and disease prevention among
      teens will lead to improved health outcomes in the future.

PMID- 24937902
TI  - School nurse facilitated programs for families living fit.
AB  - School nurses are in a unique position to facilitate provision of knowledge to
      children and their parents regarding balanced, healthy lifestyles. Nurses can
      become empowered with the knowledge gained from reviewing obesity programs with
      demonstrated improvements in obesity-related outcomes such as Kids Living Fit
      (KLF) and Nurses Living Fit (NLF). Garnering resources from your school and
      community, school nurses can create programs using methods from KLF and NLF to
      facilitate Families Living Fit (FLF). With the provision of programs, ideally
      children and parents will also feel empowered through knowledge gained as a
      result of their participation in FLF programs focusing on healthy lifestyles,
      incorporating the balance between activities chosen/exercise and foods
      consumed/nutrition.

PMID- 24937903
TI  - Rural school nurse perception of book studies as an effective method for
      professional development.
AB  - School nurses who serve public school districts in rural Northwest Washington
      face barriers in accessing Continuing Education (CE) for professional development
      as they often practice in remote, isolated school communities. Acknowledging
      these barriers, the author discusses the inclusion of book studies within an
      existing training structure as an innovative method of providing professional
      development. By utilizing training that is already attended by rural school
      nurses, CE can be enhanced without incurring additional travel, cost, or training
      time. The school nurse's perception of the effectiveness of book studies as a CE
      method was examined per a descriptive, qualitative program evaluation. Over a
      period of 5 years, evaluation and feedback data from 12 rural school nurses were
      compiled from nine individual school nurse book study evaluations and one general
      satisfaction survey. Findings indicated overall school nurse satisfaction and
      belief that school nurse book studies are an effective and beneficial method for
      the delivery of professional development--a method that promotes collaborative
      learning and collegiality, informs practice, and provides insight into the
      broader health and social issues impacting today's students.

PMID- 24937904
TI  - Overweight and obesity in youth in schools-the role of the school nurse: position
      statement.
AB  - It is the position of the National Association of School Nurses that the
      registered professional school nurse (hereinafter referred to as the school
      nurse) has the knowledge and expertise to promote the prevention of overweight
      and obesity and address the needs of overweight and obese youth in schools. The
      school nurse collaborates with students, families, school personnel, and health
      care providers to promote healthy weight and identify overweight and obese youth
      who may be at risk for health problems. The school nurse can refer and follow up
      with students who may need to see a health care provider. The school nurse also
      educates and advocates for changes in school and district policies that promote a
      healthy lifestyle for all students.

PMID- 24937905
TI  - School violence, role of the school nurse in prevention: position statement.
AB  - It is the position of the National Association of School Nurses (NASN) that
      registered professional school nurses (hereinafter referred to as school nurses)
      advance safe school environments by promoting the prevention and reduction of
      school violence. School nurses collaborate with school personnel, health care
      providers, parents, and community members to identify and implement evidence
      based educational programs promoting violence prevention. The curriculum used
      should improve students' communication, behavior management, and conflict
      resolution skills. School nurses assess and refer at-risk students in need of
      evaluation and treatment for symptoms of aggression and victimization.

PMID- 24937906
TI  - Office frenotomy for neonates: resolving dysphagia, parental satisfaction and
      cost-effectiveness.
AB  - OBJECTIVE: To determine parental satisfaction and cost-effectiveness of having a
      frenotomy performed in the office setting versus in the operating room under
      general anesthesia. METHOD: After obtaining IRB approval at The Children's
      Hospital of Philadelphia (CHOP), we performed a retrospective chart review of
      patients having a frenotomy in the office between 2003-2008. 55 patients met the
      criteria and 25 were consented and their parents interviewed. CONCLUSION: All
      participants reported an improvement in feeding within one day and up to two
      weeks following the procedure. Parents also reported being somewhat satisfied to
      very satisfied with having the frenotomy performed in the office versus under
      general anesthesia. There were no complications reported. Performing the
      frenotomy in the office provided patients with satisfaction as well as cost
      savings. The surgical fee for a frenotomy in the office is $850 and is the same
      as if the procedure is performed in the operating room. Performing a frenotomy
      under general anesthesia includes extra cost which consists of an anesthesia fee
      of $500-$900 and hospital charges ranging from $500-$8,000. Performing the
      frenotomy in the office on our 25 patients has resulted in a cost savings of more
      than $240,000 and the avoidance of general anesthesia in the first few weeks of
      life. Office frenotomy should be considered in children with ankyloglossia who
      present with difficulty nursing in the first week of life.

PMID- 24937907
TI  - The effects of earphones and music on the temperature measured by infrared
      tympanic thermmeter: preliminary results.
AB  - OBJECTIVES: The main aim of the study was to evaluate the effect on subjects'
      temperature measurement readings when using the infrared tympanic thermometer
      after correct earphone placement and use, with or without music transmission
      through the earphone. METHODS: A comparative study design was adopted. A sample
      of 39 healthy people was randomly divided into three groups. Subjects in all
      groups used an earphone that had been correctly placed in the right ear only:
      Group 1: listened to heavy metal music through the earphone (13 participants);
      Group 2: listened to classical music through the earphone (13 participants);
      Group 3: no music or sound was transmitted through the earphone (13
      participants). Average differences (CI 95%) and Pearson correlations for the
      temperature measured in the right ear, which was exposed to the different
      independent variables, and the left ear which was not exposed, were calculated at
      different times: (1) after 10 minutes compared to the baseline measurement; (2)
      after 30 minutes compared to the 10 minutes measurement; and (3) after 30 minutes
      compared to the baseline measurement. RESULTS: The inter-ear temperature
      correlation at the baseline was Pearson r .801 (p = .01). There was a significant
      decrease in the correlations between right and left ear temperatures in Group 1
      and in Group 3 which was demonstrated after 10 minutes of earphone use, and
      reached critical values after 30 minutes of use in all groups. The average warmth
      in the right ear, as perceived by participants after 20 minutes, was reported.
      Using the Numerical Rating Score the average was 3.3 +/- 1.3 for Group 1, for
      Group 2 was 1.9 +/- 1.3 and for Group 3 was 3.3 +/- 1.2 (p = .05). CONCLUSION:
      Within the limitations of the study, which involved a limited number of healthy
      people the results show that it is best to not measure tympanic temperature in an
      ear that has very recently had an earphone in place.

PMID- 24937908
TI  - Cryotherapy is a simple nursing intervention for oral mucositis.

PMID- 24937909
TI  - IOM recommendations--what now?

PMID- 24937910
TI  - Stock options. With essential items in short supply, what's a crew to do?

PMID- 24937911
TI  - Can you schedule happiness?

PMID- 24937912
TI  - Preventing back injuries in EMS. What's the best approach to avoiding harm to
      providers?
AB  - Reducing back injuries requires a holistic approach and investment by all
      interested parties, from front-line staff to leadership and supporting agencies.
      As a provider, take the time to ensure you are lifting and moving equipment and
      patients in a manner that protects both the patient and you.

PMID- 24937913
TI  - How to implement a social media strategy in five hours a month.

PMID- 24937914
TI  - Partnering up for a tactical response. Although the consolidation was seamless,
      the joint team is not without challenges.

PMID- 24937915
TI  - A revolution in patient transport. Feedback from the field leads Ferno to a
      patient movement breakthrough.

PMID- 24937916
TI  - Not so fast on naloxone? There's growing support for non-paramedic use, but keep
      these cautions in mind.

PMID- 24937917
TI  - Performance anxiety. Develop stage presence, and you won't be a spectacle.

PMID- 24937918
TI  - 87th president of APS.

PMID- 24937919
TI  - A matter of opinion: "They're ba-aack!".

PMID- 24937920
TI  - Congress finalizes fiscal year 2014 budgets.

PMID- 24937921
TI  - Chimpanzee update.

PMID- 24937922
TI  - Tips on how to succeed at your first experimental biology meeting.

PMID- 24937923
TI  - The other side of the submit button: how to become a reviewer for scientific
      journals.

PMID- 24937924
TI  - Brian R Duling, 67th APS President.

PMID- 24937925
TI  - Repeated administration of inhibitors for ion pumps reduce markedly tumor growth
      in vivo.
AB  - INTRODUCTION: Measurements of extracellular pH show that the micro environment of
      malignant tumors is more acidic than that of normal cells, whereas pH does not
      differ appreciable in normal and malignant cells. The acid micro environment of
      tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic
      tumor tissue. In order to survive in a low pH-environment tumor cells develop
      regulatory mechanisms which keep their intracellular pH stable. Two of the most
      important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of
      stilbenian derivatives. MATERIAL AND METHODS: Experiments were carried out on DBA
      mice of both sexes at the age of 4 month. Laboratory animals were grown in our
      institute and supplied with food and aqua ad libitum. RESULTS: After termination
      of the experiments the mean tumor diameter in the control group was 12.4 +/-
      0.8mm, in group A it was 6.9 +/- 0.6mm, and in group B we measured 6.6 +/- 3.1mm.
      At the final day the tumor size in treated animals was twice as small as in the
      control group. In addition we observed the rate of survival. In the control group
      only 18% of the animals were still alive at day 18. Considering the rate of
      survival a statistically significant difference between treated and untreated
      animals was observed. The survival of tumor cells is dependent on the function of
      these ion pumps which keep their intracellular pH values constant in the setting
      of an acid extracellular environment. CONCLUSION: The activity of the ion pump is
      especially important at the beginning of cell division and in cell proliferation.
      Our in vivo experiments demonstrate that prolonged administration of intratumoral
      ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor
      bearing animals. Research of inhibitors of ion pumps and their action in tumor
      growth opens new perspectives into pathophysiology of malignant tumors and may
      create new therapeutic options.

PMID- 24937926
TI  - Testicular volume and testicular atrophy index as predictors of functionality of
      unilaterally cryptorchid testis.
AB  - GOAL: The goal of this study was to determine relationship between the
      sensitivity and specificity of testicular volume (TV) and testicular atrophy
      index (TAI) in the indirect assessment of functional ability of cryptorchid
      testicles. MATERIAL AND METHODS: The study included sixty children with
      unilateral cryptorchidism who were treated surgically at the Clinic of Pediatric
      Surgery, Clinical Center University of Sarajevo. We evaluated the correlation of
      the size of cryptorchid testicles with its locations in various age groups.
      RESULTS: The results showed a significant decrease in TV and TAI in the all
      cryptorchid groups after the sixth month of age compared with the same parameters
      in control group (p < 0.001). It is also determined a strong correlation between
      the TV and TAI of cryptorchid testicles with its locations in various age groups.
      CONCLUSION: Our results showed that the average volume of cryptorchid testicles
      decreased after the sixth month as well as that the reduction of testicular size
      correlated with increasing distance of cryptorchid testicles from the scrotum.

PMID- 24937927
TI  - Glasgow prognostic score in patients receiving chemotherapy for non-small-cell
      lung cancer in stages IIIb and IV.
AB  - INTRODUCTION: Lung cancer is most common cause of cancer-related mortality
      worldwide. Non-small-cell lung carcinoma (NSCLC) is disease with very low 5-year
      relative survival rate. For patients with non-small cell lung cancer, roles of
      current treatments are to prolong survival time and to improve quality of life.
      AIM: The aim of the work was to compare values of Glasgow Prognostic Score (GPS)
      before application of the chemotherapy medication with response to chemotherapy
      and toxic side effects associated with chemotherapy in patients treated with
      cisplatin-etopozid (PE) and cisplatin-gemcitabin (PG) in stages IIIb and IV of
      NSCLC. Testing role of Glasgow Prognostic Score as a possible predictor of
      response to therapy and toxic side effects of chemotherapeutic protocol was
      another aim of this work. PATIENTS AND METHODS: This prospective study included
      60 patients in stages IIIb or IV of NSCLC, with ECOG < or = 2. The patients were
      divided in two groups. First group contained 30 patients treated with
      chemotherapeutic protocol using cisplatin-etopozid (PE), and the same number of
      patients in the second group were treated with cisplatin-gemcitabin (PG).
      RESULTS: Glasgow Prognostic Score (GPS) evaluation before the chemotherapy
      inclusion showed values of 1 (43.30:53.30), then 2 (40.00:36.70) and the lowest 0
      (16.70:10.00) which supports the pathological values of GPS in developed lung
      cancer, i.e. most patients had pathological GPS value in both protocols
      (83.30:90.00). Monitoring of toxic side effects and response to chemotherapy was
      done after each cycle of treatment. DISCUSSION: Results of this study revealed
      importance of GPS in selection of patients for treatment with chemotherapy.
      Patients with lower values of GPS treated using PE chemotherapeutic protocol had
      weaker response to therapy. CONCLUSION: Coefficient of correlation for therapy
      response in both chemotherapeutic protocol, compared with values of GPS before
      treatment, were not statistically significant, therefore GPS cannot be considered
      as a predictor of therapeutic on chemotherapy.

PMID- 24937928
TI  - Hypersensitivity to aeroallergens in patients with nasobronchial allergy.
AB  - BACKGROUND: Aeroallergens are the most common causes of allergy. AIM: The aim of
      this study was to determine hypersensitivity to aeroallergens in patients with
      nasobronchial allergy. METHODS: This retrospective population study included 2254
      patients with nasobronchial allergy, from late adolescents to adults. Their
      response to aeroallergens was assessed by skin prick tests. RESULTS: More
      patients had rhinitis (72.7%), than asthma (27.6%). Although majority of patients
      were female, allergy is more common in men than in women (p < 0.05). Both groups
      of patients had the greatest number of positive skin prick tests for
      Dermatophagoides pteronyssinus (27.5%) and weed pollens (21.9%), followed by
      grass (18.3%) and tree pollens (10.1%). Ragweed is the most common positive weed
      pollen in both groups, more in patients with rhinitis (p = 0.022). The cocksfoot
      is the most common grass pollen in rhinitis group (15.3%), but meadow grass
      (12.6%) in asthma patients. Birch is the most common tree allergen in the both
      groups. CONCLUSIONS: More patients with nasobronchial allergy have rhinitis than
      asthma. Skin prick tests are usually positive for Dermatophagoides pteronyssinus
      and weed pollens, followed by grass and tree pollens, and they are more common
      positive in patients with rhinitis than asthma.

PMID- 24937929
TI  - The role of fibrin glue polypropylene mesh fixation in open inguinal hernia
      repair.
AB  - The aim of this study was to compare two methods of polypropylene mesh fixation
      for inguinal hernia repair according to Lichtenstein using fibrin glue and suture
      fixation. MATERIAL AND METHODS: The study included 60 patients with unilateral
      inguinal hernia, divided into two groups of 30 patients--Suture fixation and
      fibrin glue fixation. All patients were analyzed according to: age, gender, body
      mass index (BMI), indication for surgery--the type, localization and size of the
      hernia, preoperative level of pain and the type of surgery. Overall postoperative
      complications and the patient's ability to return to regular activities were
      followed for 3 months. RESULTS AND DISCUSSION: Statistically significant
      difference in the duration of surgery, pain intensity and complications (p <
      0.05) were verified between method A, the group of patients whose inguinal hernia
      was repaired using polypropylene mesh-fibrin glue and method B, where inguinal
      hernia was repaired with polypropylene mesh using suture fixation. Given the
      clinical research, this systematic review of existing results on the comparative
      effectiveness, will help in making important medical decisions about options for
      surgical treatment of inguinal hernia. CONCLUSIONS: The results of this study may
      impact decision making process for recommendations of methods of treatment by
      professional associations, making appropriate decisions on hospital procurement
      of materials, as well as coverage of health funds and insurance.

PMID- 24937930
TI  - Use of serum levels of proinflammatory cytokine IL-1alpha in chronic hepatitis B.
AB  - BACKGROUND: The reasons for the chronic viral persistence of hepatitis B virus
      infection (HBV) are unknown, but are probably related to host immune factors.
      Cytokines play a significant role in immune defense. Interleukin-1 (IL-1) is a
      proinflammatory cytokine and some studies have demonstrated that IL-1 production
      was impaired in patients with chronic infections of hepatitis B virus, implying
      that IL-1 may play a role in viral clearance, progression of fibrosis and in
      malignant potential of HBV. In this study, along with routine laboratory tests,
      has been performed the analysis of serum levels of proinflammatory cytokine IL
      1alpha in order of better understanding and monitoring of chronic hepatitis B.
      OBJECTIVE: The aim of this study was to analyze the usefulness of laboratory
      tests, which are routinely used in the assessment of liver disease with specified
      immunological parameters in patients with chronic hepatitis B. PATIENTS AND
      METHODS: Total of 60 subjects was divided into two groups: HBV- PCR positive and
      negative group. The control group of 30 healthy participants was included. Apart
      from standard laboratory tests, the analysis included serum levels of cytokine IL
      1alpha. RESULTS AND DISCUSSION: IL-1alpha had the highest mean concentration in
      group 1-viral hepatitis C, with PCR positive test (5.73 pg/ml), and then in group
      2-viral hepatitis B, PCR negative test (5.39 pg/ml). ANOVA test proves that IL
      1alpha in the healthy group (3) was different from other groups as follows: in
      relation to group 1 statistical significance level was p <0.001 (F = 32 75 5); in
      relation to group 2 was also statistically significant at p < 0.001 (F = 182
      361); Cytokine IL-1 was statistically analyzed separately and compared by group 1
      and 2 using Student t-test for independent samples. Statistical significance was
      observed at p = 0.026. IL-1alpha was positively correlated with the duration of
      the illness (p < 0.01) and with serum ALT activity (p < 0.01) and serum AST
      activity (p < 0.01). Using multivariate analysis model "Factor Analysis", was
      made significant stratification predictive parameters in relation to the cytokine
      IL-1alpha, stratified significance is indicated as follows: 1. Age, 2. history of
      receiving transfusions, 3. ALT, 4. AST, 5. MELD score (negative), 6. Child-Pugh
      score (Negative). CONCLUSION: IL-1alpha was significantly elevated in
      inflammatory conditions of pronounced activity (PCR positive hepatitis). IL
      1alpha may have important role as marker of both inflammation and hepatic injury,
      particularly in the course of hepatitis B. Results suggest that inflammatory and
      immune parameters, analyzed together can significantly contribute to the
      understanding and predicting of chronic liver damage. IL-1 can be used as
      important parameter of inflammatory activity and fibrosis evaluation and
      eventually prediction of malignant transformation in chronic liver damage.

PMID- 24937931
TI  - Cutaneous silent period in the evaluation of small nerve fibres.
AB  - INTRODUCTION: High intensity cutaneous stimulus transiently suppresses tonic
      voluntary muscle activity resulting in cutaneous silent period (CSP). AIM: The
      aim of our study was to evaluate the normal values of an onset latency L1, a late
      latency L2 and a duration of CSP after stimulating sensory fibres of the median
      nerve. MATERIAL AND METHODS: This prospective study was performed at the
      Neurology Department, Clinical Center of Sarajevo University in period from
      January 1st 2013 to December 1st 2013. In our study we examined 61 subjects. The
      group included our relatives, coworkers and friends. The informed consent from
      testing subjects was obtained. RESULTS: The origin of silent period is
      stimulation of small A-delta nerve fibres. The pre-synaptic or post-synaptic
      interruption of the electrical volley to motor neurons is discussed. Median
      values of muscle activity suppression in healthy female is 55.0 ms (45.0-74.0)
      and 59.0 ms (52.0-67) male subjects. There is a correlation between the onset
      latency L1 and the late L2 latency (p < 0.03). In the on-going study it seems
      that delay of L1 and shorter muscle activity suppression might provide a sign of
      small nerve fibres involvement. CONCLUSION: The use of CSP improves the value of
      neurophysiology examination.

PMID- 24937932
TI  - Cardiotocography in the prognosis of perinatal outcome.
AB  - AIM: The objective of the study was to examine whether cardiotocography can (CTG)
      predict asphyxia of the embryo, manifested as hypoxic-ischemic encephalopathy
      (HIE), and to what extent one can rely on CTG record. MATERIAL AND METHODS:
      Retrospective research was carried out at the Clinic for Gynecology and
      Obstetrics UKC Tuzla and medical documentation from the history of mothers and
      newborns was used. The study group consisted of 68 pregnancies and newborns who
      developed HIE. The control group consisted of 40 pregnancies, which resulted in
      birth of healthy newborns--without signs of asphyxia. CTG records were analyzed,
      Apgar score, the ways of finishing delivery. RESULTS: Pathological CTG records
      (bradycardia 100, tachycardia 180, silent type of curve, late decelerations) were
      found in 45 (66.17%) cases of the study group in comparison to 11 (27.5%) in the
      control group. In the study group Apgar score in 5th minute lower than 7 had
      17.46% newborns and the highest incidence of the normally finished deliveries. We
      conclude that cardiotocography is one of the reliable methods of fetal monitoring
      in pregnancy and delivery, and that pathological CTG record very likely indicates
      the possible presence of perinatal asphyxia. CONCLUSION: Achieving a low degree
      of correlation between pathological intrapartum cardiotocography findings and
      long-term outcome of children can be achieved by rapid and adequate obstetric
      intervention and the relatively short duration of fetal acidosis, and optimal
      procedures during intensive care of newborns.

PMID- 24937933
TI  - Correlation of cervical smear and pathohistological findings.
AB  - INTRODUCTION: In endeavor to suppress the cervical carcinoma there are several
      possible approaches including measures of primary and secondary prevention. So
      far effects of these measures on the number of cases and mortality rate of
      cervical carcinoma were modest. Only exception is organized testing based on
      cytological exam of the cervical smear - Pap test, which has proven to be highly
      effective in reducing the number of cases and mortality of cervical carcinoma in
      countries with this program. Goal of this research is analysis of correlation
      between abnormal cytological test results and pathohistological diagnosis of all
      patients in the analyzed period. MATERIAL AND METHODS: Research is descriptive,
      analytical, comparative, and partly epidemiological. Results of cytological and
      pathohistological diagnostic in the period between January 1, 2009 and December
      31, 2011 were used for analysis. All analyzed patients had colposcopy exam and
      Pap test, and patients with abnormal results of this test underwent cervical
      biopsy for pathohistological diagnostics. RESULTS: We came to following results
      and conclusions: total number of L-SIL and H-SIL (PAPA III) results was 395
      (6.20%) in comparison to total sample of 5894 (92.44%) patients. There is a
      statistically significant difference in relation to PHD result of cervical biopsy
      after L1-SIL and H-SIL (PAPA II and IV), and highest statistical margin is in
      relation of CIN II changes to cytological findings, issued at Clinic of
      Obstetrics and Gynecology and other health institutions. We come to conclusion
      that the highest percentage of patients with L-SIL and H-SIL findings is in age
      group between 0-29 years old. Statistical analysis has shown a positive trend in
      number of younger patients with L-SIL and H-SIL (PAPA III and IV), with average
      age of patients in 2011 being 31.12 +/- 9.12 years old.

PMID- 24937934
TI  - Rates and indicators for amniotomy during labor--a descriptive cross sectional
      study between primigravidas and gravida 2 and above.
AB  - BACKGROUND: Artificial rupture of membranes (Amniotomy) is a common obstetric
      intervention. Its rates and indications had been subjected to criticism in
      medical literature. The current practices recommend to reduce its rate and keep
      the birthing process as natural as possible. AIM: This observational study aimed
      to describe the rates and indicators for practice of artificial rupture of
      membranes (Amniotomy) during normal labor and to determine if any significant
      differences existed between women who have had one pregnancy (PG) and women who
      have already delivered two or more children (G2 and above) on this obstetric
      interventions: artificial rupture of membranes (ARM). RESULTS: There were no PG
      participants with ruptured membranes whereas slightly more than half of the G2
      and above participants (n = 88) had ruptured membranes. The most frequent cause
      for ARM was active management of latent phase of labor (PG n = 20 and G2 and
      above n = 9). Furthermore, slow progress of labor (PG n = 17 and G2 and above n =
      7) and concerns with fetal heart rate (PG n = 13 and G2 and above n = 5) had the
      next highest number of occurrences. Results from the proportions tests revealed
      that there was one significant difference between gravidity groups on the
      frequency of APH (p = 0.039). That is, G2 and above participants had amniotomy
      done for APH (5 of 32 = 15.63%) significantly more often than PG participants (4
      of 89 = 4.49%). And although not statistically significant (p = 0.084), there
      were 21 cases within the PG group where ARM was performed for no specific reason
      (21 of 89 = 23.6%) compared to three cases within the G2 and above group (3 of 32
      = 9.4%). CONCLUSIONS: Although ARM is a commonly performed procedure during
      labor, there is not much difference between its indications between PG and G2 and
      above. The only significantly different indication was antepartum hemorrhage
      which was higher in G2 and above. Amniotomy was also performed without any clear
      indication in 26.4% of PG and 9.4% of G2 and above. Considering ARM as obstetric
      intervention efforts should be done to reduce its rates. There is a need for
      arranging normal labor workshops to revise the indications and reviewing the
      rates after these workshops to reduce the rates of ARM.

PMID- 24937935
TI  - Correlation between retinal nerve fiber layer and disc parameters in glaucoma
      suspected eyes.
AB  - GOAL: The aim of the study was to estimate the diagnostic accuracy of optical
      coherence tomography parameters in normal, preperimetric, developed perimetric
      and terminal glaucoma. METHODS: 180 eyes of 140 consecutive patients were
      evaluated in this retrospective cross sectional pilot study. Copernicus Spectra-
      domain optical coherence tomography with resolution of 3 mm obtained through the
      optic nerve head were included. All examined eyes were divided into four groups
      (healthy eyes, initial, preperimetric glaucoma, developed perimetric glaucoma and
      terminal glaucoma). RESULTS: The highest value of the RIM is noticed in control
      group 1.44 (1.21-1.70). There is no significant difference in the size of the
      disc in the eyes with developed open angle glaucoma (1.80 +/- 0.66) compared to
      normal eyes (p = 0.663), to the eyes with initial glaucoma (p = 0.120), and
      terminal glaucomatous atrophy (p = 0.068). There is statistically importance of
      E/D parameter in healthy group 0.17 (0.04-0.27), early glaucomatous group 0.44
      (0.35-0.51), developed glaucoma 0.47 (0.39-0.61) respectively p < 0.005. The
      volume of cup was significantly greater in the eyes with terminal glaucomatous
      atrophy 1.05 (0.85-1.4) compared to the healthy eyes 0.31 (0.06-0.51) (p <
      0.005), significantly greater to initial glaucoma 0.84 (0.58-1.12) (p = 0.007)
      and significantly higher compared to developed glaucoma 0.82 (0.62-1.07) (p =
      0.003). There is no significant difference in the cup between the eyes with early
      and developed glaucoma (p = 0.912). The eyes with terminal glaucoma had
      significant lower value of the thickness of retinal nerve fiber layer 56.50
      (45.50-71.25) compared to developed glaucoma group 82.5 (72-95.75), initial
      glaucoma 110.50 (102-123) and healthy eyes 132 (119-150) (p < 0.005). CONCLUSION:
      The SD-OCT scanning should be used to quantify optic nerve head anatomy in human
      eyes. The changes can be recognized and can indicate as important risk factor in
      considering glaucoma changes. It also should be considered as an exact model of
      glaucoma pathology.

PMID- 24937936
TI  - The safety and efficacy of day care cataract surgery.
AB  - PURPOSE: To evaluate safety and efficacy of day care cataract surgery in
      developing country. PATIENTS AND METHODS: This prospective study included 200
      patients planned for cataract surgery during October and November 2012 divided in
      to two groups, day care cataract surgery (DCCS) and inpatient cataract surgery
      (ICS), with same number of male and female patients right and left eyes. All
      patients had same operative conditions and postoperative follow up. RESULTS: The
      average age of patients in this study was 68.4 +/- 7.47 years. Visual acuity
      before cataract extraction was 0.1754 where 44.5% of patients had severe visual
      impairment and another 23% had complicated cataract. Posterior capsule rupture
      was noted in 4.5% of cases. The main risk factors in both groups were: higher
      age, female gender, left side, complicated cataract, higher dioptric power of IOL
      and ECCE. Regular control opthalmologic examinations 30, 90 and 180 days after
      the cataract extraction did not reveal signs bullous keratopathy, wound
      dehiscence, cystoid macular edema and endophtalmitis in any of patients.
      Postoperative visual acuity 180 days after the operation in DCCS was 0.920 +/-
      0.154 and 0.928 +/- 0.144 in ICS. Visual acuity less than 0.5 was noted in 4.5%
      due to posterior eye segment changes. Patients in DCCS group had 30 control
      examinations more and 95 days of hospitalization less than ICS with 16.5% cost
      reduction. CONCLUSION: The concept of day care cataract surgery is equally safe
      and more cost effective than inpatient cataract surgery.

PMID- 24937937
TI  - Short-term results after local application of steroids and anesthetics in
      patients with painful spine conditions.
AB  - INTRODUCTION: Spinal pain is the most common of all chronic pain disorders.
      Imaging studies can be used to determine whether a pathological process is
      associated with the patient's symptoms. OBJECTIVE: To determine the short-term
      efficiency of local instillation of steroids in patients with painful spine
      conditions. MATERIALS AND METHODS: A prospective study included 35 patients with
      diagnosis of lumbar or cervical radiculopathy, or cervical and lumbar syndrome at
      the Department for the Physical Medicine and Rehabilitation, Department for the
      Orthopedics and Traumatology, and Department for the Neurosurgery, Clinical
      Canter University of Sarajevo (KCUS). A clinical examination, visual pain scale
      (VAS) and Oswestry Disability Index (ODI) were performed prior to the needle
      procedure and seven days after it. Descriptive and comparative statistics were
      used for comparison of pre and post-interventional results. This procedure was
      done for the first time in our region. RESULTS: The males and females were
      equally represented in this study (17:18). The patients were 29 to 80 years old.
      The highest number of patients have been between 40-60 years, older then that
      have been 44.2% of patients, and younger only 8.5%. Patients have complained
      about the radicular pain along the legs or arms or back or neck pain. Most of
      them had disc herniation-57.14%, 8.57% had bulging disc, 8.57% had spinal canal
      stenosis, 5.71% had fasetarthrosis, rest of them had combination of those
      conditions. There was a statistically significant difference between the value of
      ODI score before procedure and 7 days later (26 +/- 10:16 +/- 12; p < 0.001). The
      difference was also statistically significant in VAS values (7 +/- 1:1 +/- 1; p <
      0.001). DISCUSSION: Our study suggests that needle instillation of steroid and
      lidocaine is effective in short-term pain occurs in different painful spine
      conditions (Sy cervicale, lumbare and radiculopathy). It is valuable alternative
      to the classic methods of physical and drug therapy. It can also postpone
      surgical treatment, and it is very useful in situations of diffuse degenerative
      changes when is very important to define exact source of pain, like for instance
      in hip-spine syndrome.

PMID- 24937938
TI  - Assessment of the effects of rehabilitation after cerebrovascular accident in
      patients with diabetes mellitus and hypertension as risk factors.
AB  - AIM: The aim of this study is to evaluate the results of rehabilitation, to
      determine the prevalence of major risk factors in cerebrovascular accident and
      their consequences, as well as to propose measures and procedures that will
      affect the better rehabilitation. METHODS: The survey analyzed: age, sex,
      duration of rehabilitation, activities in daily life through the Barthel index at
      admission and at discharge, presence of risk factors HTA and DM. The study
      included a total of 116 patients, the majority of patients are older than 61
      years. We had 49% of male patients and 51% of female patients and they spent 31
      40 days at the rehabilitation. RESULTS: The most common risk factor is HTA (83%)
      and diabetes (33%). Most of the patients at admission had a BI from 0 to 4
      (32.7%), and at discharge BI in the range 17-20 (36.2%). Statistical analysis
      shows that there is a statistically significant correlation between the BI at
      admission, BI at discharge and risk factors of HTA and diabetes mellitus.
      CONCLUSIONS: The rehabilitation results in most patients is good results of
      rehabilitation. The most important risk factors in patients are HTA, DM and
      directly affect on results of rehabilitation. For the better results we should
      have energetic fight against risk factors for HTA and DM through primary and
      secondary prevention and patient education about early detection and treatment of
      these risk factors.

PMID- 24937939
TI  - Physical therapy and splinting after flexor tendon repair in zone II.
AB  - INTRODUCTION: Early physical therapy and splinting after flexor tendon repair in
      zone II is very important to improve tendon healing, increase tensile strength,
      decrease adhesion formation, early return of function and less stiffness and
      deformity. We conducted a study to observe and record the results of early active
      mobilization of repaired flexor tendons in zone II. MATERIALS AND METHOD: This
      study reports the results of physical therapy and splinting which was applied to
      75 patients with 76 digits after flexor tendon repair in zone II, treated at the
      Department of Plastic Surgery and Physical and Rehabilitation Medicine Clinic,
      Pristine-Kosovo. Physical therapy and splinting started the first day after
      surgery and have lasts until week 12. Patients were evaluated with regarding to
      the range of motion and grip strength. The assessments were done at the 8, 10, 12
      weeks and the finale assessments were done after 6 months. RESULTS: Range of
      motion after 6 months according to the Strickland Classification were excellent
      in 21.1%, good in 44.7, fair in 11.8% and poor in 22.4%. Grip strength was good
      in 63.8% of cases. CONCLUSION: Results of this study shows that using a physical
      therapy and splinting achieve good results in range of motion, muscle force and
      early return of function of the hand.

PMID- 24937940
TI  - Urinary biomarkers of acute kidney injury in patients with liver cirrhosis.
AB  - BACKGROUND AND AIM: Acute kidney injury is a common complication in cirrhotic
      patients. Serum creatinine is a poor biomarker for detection of renal impairment
      in cirrhotic patients. The aim of this study was to evaluate Urinary Neutrophils
      Gelatinase-Associated Lipocalin (NGAL) and Urinary interleukin-18 (IL-18) as
      early biomarkers of acute kidney injury in cirrhotic patients. PATIENTS AND
      METHODS: 160 cirrhotic patients was enrolled in this study divided into 3 main
      groups according to presence or absence of ascites and renal impairment. RESULTS:
      Significant elevation of both Urinary NGAL and Urinary IL-18 in cirrhotic
      patients with renal impairment especially in patients with Acute tubular necrosis
      (ATN) was observed. AUROC was (0.909) with (sensitivity 95.5%, specificity 76.1)
      for Urinary NGAL and AUROC was (0.975), with (sensitivity 95.5%, specificity
      91.3%) for Urinary IL-18. CONCLUSION: Both Urinary NGAL and Urinary IL-18 can act
      as urinary biomarkers of acute kidney injury in cirrhotic patient.

PMID- 24937941
TI  - Prevalence of acute blood transfusion reactions in Mazandaran Heart Center, Sari,
      Iran, 2010-2012.
AB  - INTRODUCTION: Although blood transfusion is life saving for patients, it is
      responsible for a series of complications and exposes the patients to a variety
      of risks. Therefore knowing different adverse effects of blood transfusion
      represents a great issue in managing recipient patients. AIM: The aim of the
      present work was to study the prevalence of blood transfusion complications among
      patients in the Mazandaran Heart Center, Sari, Iran, during a period of 2 years.
      MATERIAL AND METHODS: A retrospective review of all reported and evaluated acute
      transfusion reactions during a 2 years period in Mazandaran Heart Center was
      performed. Associated clinical signs and symptoms were evaluated. RESULTS: In
      9193 transfused blood products, there was 34 (0.4%) acute transfusion reactions.
      The commonest were discomfort and restlessness (0.16%), dyspnea (0.16%), rigors
      (0.13%), fever (0.08%), chest pain (0.06%), rash or urticaria (0.04%), nausea and
      vomiting (0.03%), palpitation (0.03%), hypertension (0.03%) flashing (0.02%),
      hypotension (0.02%). CONCLUSION: Acute transfusion reaction is seen in %0.4 of
      transfused patients therefore, we recommend a well-structured program for
      monitoring adverse reactions associated with blood transfusion and blood product
      administration (Hemovigilance program).

PMID- 24937942
TI  - Platinum-based chemotherapy in recurrent high-grade glioma patients:
      retrospective study.
AB  - INTRODUCTION: To investigate the efficacy of platinum-based chemotherapy in
      patients with recurrent high-grade glioma (HGG) who had received previous
      alkylating line of chemotherapy. MATERIAL AND METHODS: Case notes of patients who
      had received chemotherapy with carboplatin or cysplatin for recurrent HGG between
      June 2006 and July 2012 were reviewed. Baseline characteristics and outcomes
      after treatment were recorded. RESULTS: Forty-eight patients received
      carboplatin/cysplatin as second line chemotherapy for recurrent HGG (grade III n
      = 6; grade IV n = 42). The median number of cycles completed was 4. Fifteen
      patients (28%) had at least minor response, 22 (49%) had stable disease and 11
      (23%) had progressive disease. Six month progression-free survival was 30% (52%
      in patients with grade III glioma and 18% in patients with grade IV glioma). The
      median time to disease progression from the first treatment with platinum drug
      was 3.2 months. The median survival was 8 months (10 months for patients with
      grade III glioma and 7 months for patients with grade IV glioma). Among patients
      with either stable disease or a partial response, the median survival was 12
      months compared with 3 months in patients with progressive disease. No survival
      or response rate differences were noted regarding the type of previous
      chemotherapy, nitrosoureas or temozolomide. CONCLUSIONS: Single-agent
      carboplatin/cysplatin has modest activity in patients with recurrent HGG
      previously treated with one line of chemotherapy, nitrosoureas or temozolomide.
      Despite the improvement of median survival of patients achieving stable disease
      or a partial response to treatment, more effective regimens are required for this
      patient population.

PMID- 24937944
TI  - [Unselective single embryo transfer: chances of pregnancy related to operator
      experience].
AB  - BACKGROUND: Selection of best quality embryo aims to achieve higher success rate,
      the pregnancy is unique and therefore obstetric risks are reduced. OBJECTIVE: To
      evaluate the pregnancy rate with no transfer of selected single embryo (TSSE)
      three days versus the experience of the physician performing the embryo transfer.
      PATIENTS AND METHODS: A retrospective, cross-sectional observational study in 159
      patients Mexican Fertility Center in CEPAM protocol in vitro fertilization any
      indication, other ovulatory disorders and who was only possible obtain an embryo
      to be transferred in three day. For the analysis were grouped according to age,
      number of cells of the embryo transfer day and the doctor performed. Continuous
      variables are reported as means and standard deviations and univariate logistic
      regression was performed to determine statistical significance. Categorical
      variables were evaluated in frequencies and percentages. The calculations were
      performed with the software JMP. RESULTS: Protocol of single-embryo transfer not
      selected in three day pregnancy rate of 17% was obtained, with lower rates in
      women over 40 years of age and older embryos of more than 9 cells but also higher
      rate abortion. More experienced doctors achieved better pregnancy rates.
      CONCLUSION: This is the first study in Mexican population to assess the
      possibility of pregnancy with single embryo transfer in selected post-harvest
      with a three day success rate of 17% and first-order variables: number of cells
      on the day of transfer and experience of the physician who performed the
      procedure.

PMID- 24937943
TI  - Anesthetic management of hysterosalpingooophorectomy in a case with severe
      idiopathic dilated cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy is a primary myocardial disease with unknown
      aetiology. This disease follows a prospective course that is characterized by
      ventricular dilation and impaired myocardial dilation. Congestive heart failure
      and malignant arrhythmias are the most widespread complications. The incidence of
      idiopathic dilated cardiomyopathy in the general population is 5-8/100.000.
      Because of the increased risks of perioperative complications, anesthetic
      management of this disease requires the application of a specific technique. This
      case report demonstrates the application of successful regional anesthetic
      management (thoracic epidural anesthesia) in a patient who had been diagnosed
      with severe idiopathic dilated cardiomyopathy.

PMID- 24937945
TI  - [Health staff performance taking of smear: knowledge, skills and practice].
AB  - BACKGROUND: The quality of cervical cytology is one of the factors involved in
      the optimal performance of screening programs for cervical cancer in Mexico, so
      it is necessary to design indicators to improve the skills of health personnel in
      this procedure. OBJECTIVE: To evaluate the performance of the health workers to
      take the Pap smear. MATERIAL AND METHODS: Cross-sectional study made in the
      period 2006-2007 in San Luis Potosi, Mexico, in 21 health centers in a health
      jurisdiction. We studied the universe of professionals who take the Pap: 100
      nurses, doctors and interns. A knowledge test and a check list were applied. The
      correlation of Pearson, Student's t and ANOVA was used for data analysis.
      RESULTS: There is a correlation between knowledge and qualification in the take
      of the Pap smear (r = 0.340) (p = 001). Providers have a performance on average
      62.2% in knowledge and 78.5% in practice. Doctors obtained knowledge that the
      nurses (6.80) (p = .000) and trainees (4.14) (p = 014). In the practical
      implementation, there was no difference between the doctors and the nurses (2.68)
      (p = .718) but there was difference between the doctors and interns (6.47) (p =
      .036). To know one or more sections of the knowledge influences the qualification
      of the procedure. CONCLUSIONS: The performance of the service provider is
      regular. There is heterogeneity in the knowledge and practical skills.
      Educational interventions are needed to raise the skills.

PMID- 24937946
TI  - [Ovarian stimulation with gonadotropins: comparison between recombinant FSH plus
      menotropins versus recombinant FSH + LH].
AB  - BACKGROUND: Nowadays various assisted reproduction ovarian stimulation schemes
      are used for different clinical outcomes is interesting to compare. OBJECTIVE:
      Compare two ovarian stimulation protocols: recombinant FSH + LH versus
      recombinant FSH + Menotropins. MATERIAL AND METHODS: Observational, retrospective
      study, 38 cycles were analyzed, made from 2010 until 2013, assigned to two groups
      (n = 19 each), group 1 received FSHr + LHr, group 2 received FSHr + menotropins.
      Study variables were: days of ovarian stimulation, total gonadotropin dose,
      retrieved oocytes, fertilization rate, pregnancy rate and number of vitrified
      embryos. RESULTS: Fewer stimulation days (8.5 +/- 1.5 vs 9 +/- 1.1) were found in
      group 1 (recombinant gonadotropins). Group 2 (FSHr + Menotropins), had a greater
      total dose of gonadotropins (1930.2 +/- 346.2 vs 2000 +/- 418.8) and more
      retrieved oocytes (8.15 +/- 3.9 vs 8.57 +/- 4). Group 1 patients had higher
      pregnancy and fertilization rates (56.2 vs 36.8%, and 75.4 vs 69.3%)
      respectively, no statistical significance was found. CONCLUSION: This study found
      higher pregnancy and fertilization rates in patients treated with recombinant
      gonadotropins (FSH + LH) for ovarian stimulation.

PMID- 24937947
TI  - [Comparative study between pregnancies induced for premature rupture of membranes
      and for prolonged pregnancy].
AB  - BACKGROUND: To decrease maternal and fetal morbidity oftem is indicated the
      elective termination of pregnancy; when the cervix is unfavourable, it is
      possible to try to artificially reproduce these changes with exogenous
      prostaglandins. OBJECTIVES: Comparative evaluation of maternal and fetal results
      between patients in which cervical ripening is practiced with indication of
      premature rupture of membranes and those with prolonged pregnancy. MATERIAL AND
      METHOD: Historic cohorts study about pregnancies requiring cervical ripening,
      either for premature rupture of membranes or for gestational age > or = 41 weeks,
      in the "Miguel Servet" Hospital (Zaragoza, Spain), from 15/11/2005 to 15/05/2008.
      In all the cases dinoprostone (slow release vaginal system) was employed and the
      initial Bishop score was < 7. The main analysed outcomes were: intrapartum fetal
      heart monitoring characteristics, type of delivery, umbilical artery pH, Apgar
      score, hospitalization in neonatal unit requirement and time from cervical
      ripening start to delivery. RESULTS: Neonatal hospitalization was significantly
      more frequent in the ruptured membranes cohort (11.70% vs 2.33%); p = 0.001. This
      difference could be justified by gestational age (OR: 2,623. IC: 0.515-13.353. P
      = 0.246). It was observed more time cervical ripening - delivery in prolonged
      pregnancies cohort (25.96h vs 20.11h); p < 0.001. Umbilical cord medium pH was
      significantly superior in ruptured membranes group (7.25 vs 7.23); p = 0.017. No
      significant differences were observed in the rest of analyzed outcomes.
      CONCLUSIONS: Pregnancies electively ended for premature rupture of membranes are
      associated with a shorter time to delivery and a slightly superior umbilical cord
      pH than induced prolonged pregnancies. Neonatal hospitalization requirement is
      determined by gestational age but not by the rupture of the membranes. Cervical
      ripening in those patients has been demonstrated to be secure and effective.

PMID- 24937948
TI  - [Endocopic fetal surgery].
AB  - At present, the fetus is already considered a "patient" and as such, can develop
      diseases with fatal outcome in which the only therapeutic option can be fetal
      surgery. Currently, fetal surgery is limited almost exclusively to endoscopic
      surgery. Different techniques have gained clinical acceptance for improving the
      prognosis of various lethal fetal pathologies. Laser therapy for twin to twin
      transfusion syndrome and cord occlusion in monochorionic twins with selective
      intrauterine growth restriction are the procedures of choice for the management
      of monochorionic twins complications, and are associated with survival rates of
      up to 80-90% for at least one fetus. In fetuses with isolated congenital
      diaphragmatic hernia and severe pulmonary hypoplasia, fetal endoscopic tracheal
      occlusion has shown to improve the survival probabilities from 5% to 55% and from
      1% to 33% in left and right congenital diaphragmatic hernia, respectively, and a
      decrease in the rate of pulmonary hypertension and neonatal morbidity. In
      selected cases with low urinary tract obstruction (megacystis) and without renal
      failure; fetal cystoscopy is a diagnostic method that excludes the possibility of
      urethral stenosis or atresia and may be used to ablate posterior urethral valves
      by laser, restoring urethral patency and potentially preserving respiratory and
      bladder function. In fetuses with pulmonary masses, either primary or due to
      airway obstruction, there is high risk of fetal death due to cardiac compression
      and contralateral pulmonary hypoplasia. In such cases fetal bronchoscopy can
      provide a successful therapeutic option to release airway obstruction.

PMID- 24937949
TI  - [Acute appendicitis during pregnancy: report of 4 cases].
AB  - BACKGROUND: Acute appendicitis is the more frequent no obstetric surgical
      emergency during pregnancy with an incidence of 1 in 1500 pregnancies. The
      clinical diagnosis is difficult because of the physiological changes of pregnancy
      itself. If not treated early increases the risk of maternal and fetal morbidity.
      OBJECTIVE: To describe the diagnosis and treatment of four cases of acute
      appendicitis during pregnancy. CLINICAL CASE: Four cases of acute appendicitis
      during pregnancy diagnosed in the period of a month. Gestational age at diagnosis
      of appendicitis was between 8 and 13 week. All patients underwent laparotomy;
      three cases were appendicitis phase II and one phase III. The preoperative was
      managed with indomethacin and ceftriaxone. There were no maternal or obstetric
      complications. CONCLUSIONS: An early diagnosis and treatment of acute
      appendicitis during pregnancy, and a multidisciplinary approach between surgeon,
      obstetrician and anesthesiologist is the basis for success in the management of
      these patients.

PMID- 24937951
TI  - [Leiomyomatosis peritonealis disseminate. Laparoscopic management].
AB  - Leiomyomatosis peritonealis disseminata constitutes a rare pathology of an unkown
      etilogy. It is chararacterized by the appearence of multiple pelvic and abdominal
      nodules, which are basically composed of smooth muscle. The first case was
      published in 1952 by Wilson and Peale although was Tubert, in 1965, the first who
      identified this disease as a pathology. Currently, around 100 cases can be found
      in literature. We present, as far as we know, the first case resolved by
      laparoscopic technique plus gonadotropin-releasing hormone agonist therapy.

PMID- 24937950
TI  - [Primary carcinoma of the peritoneum. Case report and literature review].
AB  - Peritoneal primary carcinoma is an unusual tumor originated on the pelvic and
      abdominal peritoneal surface. It is believed that it is originates from a
      secondary mullerian system giving place to a peritoneal primary carcinoma very
      similar to the epithelial ovarian cancer in its clinical presentation,
      histological aspect, spread patron and its treatment and prognosis. It's complex
      clinical presentation difficult the differentiation from an epithelial tumors
      from the ovary. Both tumors present ascitis, elevated CA 125 and signs of
      peritoneal carcinomatosis on the tomographic images. In this report is exposed
      the case of a 39 years old women with a pre-surgical diagnosis of primary
      carcinoma of the ovarian, wich was discarded during surgery founding that the
      primary tumor was on the peritoneal surface of the descending colon.

PMID- 24937952
TI  - [Atypical preeclampsia: case report].
AB  - BACKGROUND: Preeclampsia that occurs at < 20 weeks of gestation is rare and has
      been usually reported with molar or hydropic degeneration of the placenta and
      antiphospholipid syndrome. CASE REPORT: To describe the clinical presentation of
      atypical preeclampsia of a patient of 37 years old at her first gestation who
      developed this entity at 18.5 weeks of gestation. She had history of pre-existing
      hypertension and infertility. This pregnancy was obtained through in vitro
      fertility. She reported a severe headache and was admitted to our hospital
      secondary to elevated blood pressure of 160/110 mm Hg. The laboratory evaluation
      revealed platelet count 51,000, alanine aminotransferase of 331 UI/L, aspartate
      aminotransferase of 285 UI/L, lactate dehydrogenase 421 UI/L and urinalysis with
      +2 proteinuria, soluble fms-like tyrosine kinase-1/placental growth factor ratio
      895.5. The diagnosis of chronic hypertension and superimposed preeclampsia and
      incomplete HELLP syndrome was supported. After termination of pregnancy, the
      patient improved rapidly. She was discharged home on postoperative day 7 with a
      blood pressure of 120/70 mm Hg with normal laboratory. CONCLUSIONS: Clinicians
      should consider the diagnosis of preeclampsia and HELLP syndrome before 20 weeks
      of gestation in women presenting with clinical or laboratory abnormalities
      consistent with this disease.

PMID- 24937953
TI  - [Some considerations of venous thrombosis and pulmonary embolism. 1958].

PMID- 24937954
TI  - Gestational trophoblastic disease: presentations from the XVIIth World Congress
      on Gestational Trophoblastic Diseases.

PMID- 24937955
TI  - Subsequent pregnancy outcomes after complete and partial molar pregnancy,
      recurrent molar pregnancy, and gestational trophoblastic neoplasia: an update
      from the New England Trophoblastic Disease Center.
AB  - OBJECTIVE: To review and update the subsequent reproductive outcomes in patients
      with complete, partial, and recurrent hydatidiform moles, as well as gestational
      trophoblastic neoplasia (GTN) at the New England Trophoblastic Disease Center.
      STUDY DESIGN: Patients with complete and partial hydatidiform mole, recurrent
      hydatidiform mole, and GTN were identified from the Donald P. Goldstein, M.D.,
      Trophoblastic Tumor Registry. Questionnaires regarding subsequent pregnancies
      were mailed to patients with current mailing addresses available. Additional
      patient data was obtained from electronic medical records. RESULTS: A total of
      2,432 subsequent pregnancies have been reported since 1965. Of those, 1,388
      pregnancies were after complete mole, 357 after partial mole, and 667 after GTN.
      The subsequent reproductive outcomes in patients with complete and partial molar
      pregnancies and persistent GTN remain similar to those in the general population.
      However, approximately 1.7% of patients with a prior molar pregnancy had a molar
      pregnancy in a later gestation. Furthermore, after successful chemotherapy for
      GTN the incidence of stillbirth was slightly increased to 1.3% in later
      pregnancies. CONCLUSION: Patients with molar pregnancies and GTN should expect
      similar reproductive outcomes as compared to the general population. However,
      patients receiving chemotherapy for GTN have a slightly increased risk stillbirth
      in subsequent pregnancies.

PMID- 24937956
TI  - Evolution of a specialist gestational trophoblastic disease service with a major
      nursing component: the Sheffield, United Kingdom, experience.
AB  - OBJECTIVE: To describe the evolution of a highly regarded and unique model of
      multidisciplinary care providing support, monitoring, and treatment for all
      gestational trophoblastic disease (GTD) patients referred to Sheffield
      Trophoblastic Disease Centre, 1 of the 3 United Kingdom (UK) supraregional GTD
      centers. BACKGROUND: The UK GTD service was first established in 1973 and since
      its inception has centralized care for GTD patients and played a leading
      international role in developing therapies, management protocols, and biomarker
      assays with good outcomes for patients. The service preceded recent trends
      towards centralization for rare cancers in the U.K. In Sheffield the GTD team has
      evolved to become a true multidisciplinary team with a strong nursing component,
      which is set to expand in the future. RESULTS: Centralization of care for GTD in
      the U.K. has been directly associated with the impressive results the service has
      achieved, with high cure rates (98-100%) and low (5-8%) chemotherapy rates. The
      addition of GTD nurse specialists has been beneficial to patients as they provide
      a communication link between patients and their clinicians and ensure that
      information, support, and advice is available for all GTD patients, both in
      hospital and at home. CONCLUSION: The UK GTD service is an internationally
      renowned, multidisciplinary organization. The service achieves impressive
      clinical results and now features a strong nursing component. The addition of
      nurse specialists has enabled the team to offer both clinical and psychological
      care and means that specialist advice is available for patients and healthcare
      professionals involved in giving care to this patient group.

PMID- 24937957
TI  - Hepatic metastasis in gestational trophoblastic neoplasia: patient
      characteristics, prognostic factors, and outcomes.
AB  - OBJECTIVE: To identify patient characteristics, determine prognostic factors, and
      evaluate outcomes for women with hepatic metastases in gestational trophoblastic
      neoplasia (GTN). STUDY DESIGN: Seventeen GTN patients with hepatic metastases
      were treated at our institution between 1962 and 2010. Demographic data, disease
      characteristics, and survival were all analyzed retrospectively. Fisher's exact
      test was used to determine significance. RESULTS: The median age was 29 years
      (range, 16-48), and the antecedent pregnancy was nonmolar in 12 patients (75%)
      and a hydatidiform mole in 4 patients (25%). Fifteen patients (88%) had
      metastatic disease outside the liver, including lung (13), brain (5), and other
      intraabdominal organs (8). Median FIGO score was 14 (range, 12-19). Chemotherapy
      consisted of single-agent methotrexate or actinomycin D in 2 patients;
      methotrexate, actinomycin D, cyclophosphamide (MAC) in 4 patients; and etoposide,
      methotrexate, actinomycin D, cyclophosphamide and vincristine (EMACO) in 11
      patients. Complete response rate to chemotherapy was 82% for EMA-CO versus 17%
      for other types of chemotherapy (p = 0.035). Overall survival was 41% (7/17).
      CONCLUSION: Survival of patients with GTN and hepatic metastases increased from
      17% (1/6) to 55% (6/11) after 1986 when EMA-CO chemotherapy was introduced.
      Survival was significantly decreased for patients with concomitant intraabdominal
      or brain metastases (11% vs. 75%, p = 0.015).

PMID- 24937958
TI  - Reproductive outcomes after multiagent chemotherapy for high-risk gestational
      trophoblastic neoplasia.
AB  - OBJECTIVE: To analyze the reproductive outcomes of women with high-risk
      gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO
      chemotherapy. STUDY DESIGN: Of 212 patients treated with chemotherapy for GTN
      between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and
      consented to participate in a questionnaire designed to assess their menstrual
      and reproduction outcomes. RESULTS: Twenty-four high-risk (HR) and 41 low-risk
      (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had
      not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could
      recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed
      menses after chemotherapy. Both groups also had a similar age of menopause (HR,
      43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group
      desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%])
      (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p
      = 0.03), with equivalent live birth rates of 74% and 76%, respectively.
      CONCLUSION: Multiagent EMA-CO chemotherapy did not significantly alter menstrual
      or reproductive outcomes compared to single-agent methotrexate chemotherapy for
      GTN.

PMID- 24937959
TI  - Determining the time required to achieve negative human chorionic gonadotropin
      value after a nonmolar pregnancy: preliminary results.
AB  - OBJECTIVE: To determine the time of human chorionic gonadotropin (hCG) regression
      in nonmolar gestation. STUDY DESIGN: Patients treated at our institution between
      June 2012 and July 2013 were selected by a deterministic sequential sampling
      distributed among 2 phases. Distribution of the patients included resolved cases
      by vaginal delivery and cesarean section in preterm and term pregnancies,
      ectopic, and abortion. Phase 1: serum hCG values were determined at 4, 5 and 6
      weeks of obstetric resolution. Phase 2: hCG serum values were determined
      immediately at obstetric resolution and at 2, 3 and 4 weeks of the resolution of
      the cases, too. RESULTS: Phase 1: After the analysis of serum hCG of 63 patients
      at 4, 5 and 6 weeks postresolution, a negative result was corroborated in 100% of
      cases, in any period of the sample, with average values of 1.71, 0.55, and 0.18
      mIU/mL, respectively. Phase 2 included 398 patients, with serum hCG in the first
      72 hours postresolution, showing an average hCG value of 1,483.5 mIU/mL (range,
      0.07-10,789), noting that 1% of cases had negative results. We then obtained hCG
      values at 2, 3 and 4 weeks of resolution, showing the regression in 73.4% of
      cases in the 2nd week, in 96.7% of patients in the 3rd week, and in all cases in
      the 4th week. CONCLUSION: The regression of hCG after nonmolar pregnancy does not
      exceed 3 weeks.

PMID- 24937960
TI  - Histopathological and immunohistochemical features of early hydatidiform mole in
      relation to subsequent development of persistent gestational trophoblastic
      disease.
AB  - OBJECTIVE: To examine histomorphological and immunohistochemical findings in
      hydatidiform moles to determine whether any features can reliably predict
      clinical behavior. STUDY DESIGN: Blinded semiquantitative review of histological
      and immunohistochemical findings in cases of partial hydatidiform mole (PHM) (N =
      50) and complete hydatidiform mole (CHM) which either spontaneously resolved (N =
      50) or required chemotherapy (N = 50). Immunostains assessed included MLH1, MSH2,
      nm23, TERT, p53, EGFR, and CerbB2 based on previous data. RESULTS: There were
      marked morphological differences in various criteria between CHMs and PHMs,
      including the proportion of villi with abnormal trophoblast hyperplasia (29% vs.
      6%, respectively). However, there were no significant differences in any
      morphological parameters between CHMs that spontaneously resolved and those that
      subsequently required chemotherapy. Similarly, there were no clinically useful
      differences regarding any immunostaining scores between CHM groups. CONCLUSION:
      Neither morphological nor immunohistochemical features can reliably predict
      subsequent requirement of chemotherapy in CHMs.

PMID- 24937962
TI  - Changes in the management of high-risk gestational trophoblastic neoplasia in the
      National Trophoblastic Disease Center of Hungary.
AB  - OBJECTIVE: To compare the clinical management of patients with high-risk
      gestational trophoblastic neoplasia (GTN) among the periods of 1977-1990, 1991
      2000, and 2001-2012 at the National Trophoblastic Disease Center of Hungary and
      to assess the efficacy of the FIGO 2000 staging and risk factor scoring system in
      comparison to the original WHO prognostic scoring system (1983). STUDY DESIGN: We
      reviewed the medical records of 185 patients with high-risk GTN. From 1977-2000,
      patients were classified according to the original WHO prognostic scoring system
      (1983). From 2001-2012, high-risk patients were categorized by the FIGO 2000
      system. We assessed the efficacy of MAC and EMA-CO primary combination
      chemotherapies. For 1977-2006 and 2007-2012 we assessed the efficacy of MAC and
      EMA-CO primary combination chemotherapies. RESULTS: From 1977-1990, 63 high-risk
      patients (average, 4-5 patients/year), from 1991-2000, 50 high-risk patients
      (average, 5 patients/year), and from 2001-2012, 72 high-risk patients (average, 6
      patients/year) were treated primarily with combination chemotherapy (MAC and/or
      EMA-CO and/or CEB). From 1977-2006, 100 high-risk patients received MAC primary
      combination chemotherapy and 17 cases received EMA-CO. The ratio of primary MAC
      primarily with and EMA-CO therapy among our high-risk patients was 5.9 (100/17)
      over the referred period. From 2007-2012, 21 high-risk patients were treated with
      primary MAC chemotherapy and 16 patients received EMA-CO. The MAC/EMA-CO ratio
      over this time interval was 1.3 (21/16). CONCLUSION: We attained complete
      remission in 95.7% of the high-risk patients. During the last 6 years the use of
      EMA-CO primary combination chemotherapy increased among our high-risk patients,
      which has resulted in increased efficacy and fewer side effects.

PMID- 24937961
TI  - The encouraging prognosis of nongestational ovarian choriocarcinoma with lung
      metastases.
AB  - OBJECTIVE: To study nongestational ovarian choriocarcinoma (NGOC) with lung
      metastases: its early diagnosis, optimal therapeutic method, and prognosis. STUDY
      DESIGN: Twelve cases of NGOC with lung metastases treated in Peking Union Medical
      College Hospital from 1982-2011 were analyzed retrospectively. The 12 cases
      included 9 pure NGOCs and 3 mixed with other germ cell tumors (mature teratoma,
      endodermal sinus tumor and embryonal carcinoma components, and dysgerminoma,
      respectively). Chemotherapy was given in all 12 cases, mainly including EMA/CO,
      BEP, and RESULTS: The median age for the cases was 23.9 years. Abdominal pain was
      the most common symptom (7/12). Follow-up was available for 11 cases, ranging
      from 17-174 months (median, 86.6 months). Of those, only 1 patient died of the
      disease, at 42 months from the disease onset. The other patient for whom follow
      up was not available gave up treatment due to chemoresistance and disease
      progression. An overall sustained remission had been achieved in 10 cases
      (83.3%). CONCLUSION: Surgery combined with the appropriate chemotherapy regimen
      can improve therapeutic efficacy and survival in the treatment of NGOC with lung
      metastasis, even in recurrent or chemorefractory cases. Commencement of EMA/CO
      chemotherapy, which seems to be associated with better prognosis, should be
      considered as a good choice of treatment. Conservative surgery is acceptable for
      young patients desiring to preserve fertility.

PMID- 24937963
TI  - Hydatidiform mole and its complications: review of patient profiles and
      management at the university of the Philippines-Philippine General Hospital.
AB  - OBJECTIVE: To describe the clinicopathologic profile of patients diagnosed with
      molar pregnancy and complications associated with the disease and their
      management at a tertiary government hospital. STUDY DESIGN: A descriptive
      retrospective review of medical records of patients diagnosed with hydatidiform
      mole for a 5-year period was done. The demographics, clinical course, management
      options and complications, monitoring and progression to malignancy, and
      histopathologic diagnosis of these patients were reviewed. RESULTS: From January
      2008-December 2012 there were 551 cases of molar pregnancies. The hospital-based
      incidence of hydatidiform mole was 13.38/1,000 pregnancies. The most common
      manifestation was vaginal bleeding, with 98% (540/551) of patients. However, 75%
      (405/540) had significant anemia described as hemoglobin level < 10 mg/dL, and
      32% (173/540) had accompanying pallor, hypotension and tachycardia. Other medical
      complications included those related to increased beta-hCG titers such as
      preeclampsia, hyperthyroidism and pulmonary insufficiency. The most common
      histopathologic diagnosis (71%) was complete hydatidiform mole. Seventy percent
      of patients were given methotrexate chemoprophylaxis, mainly due to serum hCG >
      100,000 mIU/ mL. Of the 551 patients 49 (9%) progressed to malignancy within the
      next 36 months. The mortality rate was 1.6% (9/551). The most common cause of
      mortality was hemorrhagic complication. CONCLUSION: At the Philippine General
      Hospital hydatidiform mole is not uncommon. The knowledge of the clinical course
      of the condition as well as prompt and appropriate management of complications is
      integral in its management for an excellent prognosis.

PMID- 24937964
TI  - Epidemiological report on the treatment of patients with gestational
      trophoblastic disease in 10 Brazilian referral centers: results after 12 years
      since International FIGO 2000 Consensus.
AB  - OBJECTIVE: To evaluate treatment of Brazilian patients with gestational
      trophoblastic disease (GTD). STUDY DESIGN: A retrospective cohort study with
      analysis of medical reports performed in 10 Brazilian referral centers from
      January 2000 to December 2011. RESULTS: Of 5,250 patients 3 died (0.06%) at the
      time of uterine evacuation. Spontaneous remission of GTD (group G1) was observed
      in 4,103 cases, and 1,144 (21.8%) progressed to gestational trophoblastic
      neoplasia (GTN) (G2). In G1 2,716 (66.2%) had complete hydatidiform mole (HM) and
      1,210, partial HM (29.5%); 3,772 patients (92.7%) recovered as noted in December
      2012. In G2, of 1,118 patients treated, initial histopathological results of
      previous gestation were complete HM (77.5% [n = 886]), partial HM (8.8% [n =
      100]), and choriocarcinoma (8.0% [n = 92]); 930 (81.3%) were low-risk, 200
      (17.5%) were high-risk GTN, and 14 had placental site trophoblastic tumor (PSTT)
      (1.2%); cure was achieved in 1,078 cases (96.4%), but 26 patients (2.3%) died (4
      low-risk [0.4%], 19 high-risk [9.5%], and 3 PSTT [21.4%]). CONCLUSION: The
      highest death rates were due to high-risk GTN and PSTT. Patients with molar
      pregnancy should be referred to a referral center for an early diagnosis and
      prompt treatment of GTN in order to reduce the morbidity and mortality found in
      advanced stages.

PMID- 24937965
TI  - Effect of early pregnancy following chemotherapy on disease relapse and fetal
      outcome in women treated for gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To examine the effects of early pregnancy (< 12 months following
      chemotherapy) on a recent cohort of women treated with modern therapies for
      gestational trophoblastic neoplasia (GTN). STUDY DESIGN: The Charing Cross GTN
      database was screened between 1998-2012 to identify 1,204 patients treated with
      either single-agent (61.9%) or multiagent (38.1%) chemotherapy. RESULTS: A total
      of 23% of single-agent and 15.4% of the multiagent treatment groups conceived
      within 12 months of chemotherapy, resulting in 255 early pregnancies, with 73.3%
      resulting in live births. There was no significant increased risk of miscarriage,
      ectopic pregnancy, second molar pregnancy or stillbirth as compared to the
      general U.K. population. Intriguingly, the incidence of relapse was only 1.7% in
      the early pregnancy group as compared to 5.2% in the 963 patients who did not
      conceive early. CONCLUSION: Women who become pregnant within 12 months
      postchemotherapy for GTN can be reassured of a likely favorable outcome, although
      the safest option is still to delay pregnancy for a year.

PMID- 24937966
TI  - Falling estradiol levels on day after human chorionic gonadotropin administration
      in assisted reproductive technology cycles are not predictive of decreasing
      oocyte maturity or pregnancy rates.
AB  - OBJECTIVE: To determine whether a fall in serum estradiol levels the day after
      human chorionic gonadotropin (hCG) administration correlated with the incidence
      of a positive serum hCG in fresh, nondonor assisted reproductive technology (ART)
      cycles. STUDY DESIGN: A total of 1,969 women undergoing fresh, nondonor ART
      cycles at a tertiary referral fertility clinic between January 1, 2003, and
      January 31, 2010, were included and retrospectively analyzed. Primary outcome
      measures were oocyte maturity and positive serum beta-hCG. RESULTS: A total of
      1,969 cycles met inclusion criteria, of which 1,875 had the same or increasing
      serum estradiol levels and 94 had decreasing estradiol levels on the morning
      after hCG trigger administration (6-11 hours after hCG injection). There were no
      statistically significant differences between the groups with respect to age,
      baseline FSH levels, type of pituitary downregulation, total ampules of
      gonadotropin administered, days of stimulation, average number of oocytes
      retrieved, or oocyte maturity. Probability of pregnancy in women with declining
      E2 levels after hCG trigger administration did not differ from patients with the
      same or rising estradiol levels (53% vs. 54%, p = 0.89). CONCLUSION: Absolute
      change in estradiol levels the morning after beta-hCG administration were not
      predictive of positive hCG.

PMID- 24937967
TI  - Effect of luteal phase support with vaginal progesterone in intrauterine
      insemination cycles with regard to follicular response: a prospective randomized
      study.
AB  - OBJECTIVE: To investigate the effect of luteal phase support with vaginal
      progesterone on pregnancy rates of the gonadotropin-stimulated intrauterine
      insemination (IUI) cycles in patients with unexplained infertility with regard
      tofollicular growth. STUDY DESIGN: A total of 149 patients with unexplained
      infertility who underwent 166 recombinant follicle stimulated hormone--stimulated
      IUI cycles were prospectively randomized into 2 groups for luteal phase support.
      The study group (n = 71) received vaginal progesterone gel supplementation, and
      the control group (n = 78) received no drug for luteal support. The clinical
      pregnancy rates and live birth rates per cycle and per patient were compared
      between the groups. RESULTS: The differences between the groups with regard to
      clinical pregnancy rates and live birth rates per patient or per cycle were not
      different among all patients. In cycles with > 1 dominant follicle
      (multifollicular response), the clinical pregnancy rate per patient was
      significantly higher in the supported cycles as compared with the unsupported
      cycles (28.2% vs. 11.4%, respectively, p = 0.04). Reproductive outcomes in cycles
      with a single dominant follicle (monofollicular response) were not different
      between supported and unsupported cycles. CONCLUSION: Luteal phase support with
      vaginal progesterone affects the success of gonadotropin-stimulated IUI cycles
      with multifollicular response but not with monofollicular response.

PMID- 24937968
TI  - Follicular and estradiol parameters that improve success with natural cycle in
      vitro fertilization.
AB  - OBJECTIVE: To describe clinical thresholds for follicle size and estradiol levels
      to optimize success with natural cycle in vitro fertilization (NCIVF). STUDY
      DESIGN: Descriptive cohort of candidates for stimulated IVF, < 43 years old, with
      regular menstrual cycles, regardless of ovarian reserve or fertility treatment
      history. Patients underwent NCIVF, defined as oocyte retrieval, fertilization and
      embryo transfer after human chorionic gonadotropin (hCG) trigger without
      luteinizing hormone (LH) suppression or ovarian stimulation medications. RESULTS:
      A total of 422 patients underwent 821 NCIVF cycles. Clinical pregnancy rates per
      cycle start, retrieval, and transfer were 13%, 17%, and 32%, respectively, for
      all patients and 19%, 25%, and 49% for patients < 30 years old. The threshold
      estradiol level on day of hCG was 101 pg/mL; below that level no clinical
      pregnancies occurred. Likewise, a mean follicular diameter > 15 mm was the
      optimal threshold for hCG trigger. Anti-Mullerian hormone and follicle
      stimulating hormone levels did not predict success in NCIVF, and no statistical
      difference in clinical pregnancy rates between day 3 or day 5 embryo transfer was
      observed. CONCLUSION: NCIVF is an effective therapy for infertile patients
      regardless of their ovarian reserve. Cycle cancellation due to a premature LH
      surge can be reduced, without sacrificing success, by triggering smaller
      follicles above a threshold level of estradiol.

PMID- 24937969
TI  - Fertility-sparing partial hysterectomy for gestational trophoblastic neoplasia:
      an analysis of 36 cases.
AB  - OBJECTIVE: To evaluate the success of partial hysterectomy in treating
      gestational trophoblastic neoplasia (GTN) and preserving fertility. STUDY DESIGN:
      A retrospective review was conducted on 36 patients with GTN who underwent
      adjuvant fertility-sparing partial hysterectomy at the Department of Gynecologic
      Oncology, Women's Hospital, School of Medicine, Zhejiang University, China,
      between 1991 and 2008. RESULTS: Of 36 patients, 34 had fertility-sparing partial
      hysterectomy; 2 required full hysterectomy due to excessive bleeding during
      surgery. All women went into remission from their disease. Twenty-five
      subsequently achieved clinical pregnancy, resulting in a total of 23 live births.
      CONCLUSION: Partial hysterectomy with chemotherapy can be effective in treating
      GTN while preserving future fertility. This should be considered as an option for
      women who wish to pursue pregnancy in the future.

PMID- 24937970
TI  - Emotional intelligence characteristics in a cohort of faculty, residents, and
      medical students.
AB  - OBJECTIVE: To assess emotional intelligence (EQ) and the construct validity of
      the EQ Appraisal survey among academic faculty, residents, and medical students.
      STUDY DESIGN: From 2007 to 2011, 155 medical education personnel participated in
      4 self-administered surveys. The EQ Appraisal survey measures Self-Awareness,
      Self-Management, Social Awareness, and Relationship Management. The DISC survey
      defines 4 personality domains: Dominance, Influence, Steadiness/ Submissiveness,
      and Conscientious/Compliance. The Thomas-Kilmann Conflict Instrument defines 5
      conflict styles: Competing, Collaborating, Compromising, Accommodating, and
      Avoiding. The Interpersonal Influence Inventory categorizes 4 behavior styles:
      Openly Aggressive, Assertive, Concealed Aggressive, and Passive behaviors.
      Statistical analysis was done as indicated. The p value of < 0.05 was taken as
      significant. RESULTS: The overall mean EQ score was 75.9 (SD 8.2), and components
      scores were: Self-Awareness = 74.6 (SD 10), Self-Management = 74.8 (SD 10.6),
      Social Awareness = 77.0 (SD 9.6), and Relationship Management = 76.8 (SD 9.9).
      Faculty and residents had higher Social Awareness scores as compared to medical
      students (79.33 [SD 8] vs. 75.59 [SD 10.3], p = 0.01). Mean EQ scores correlated
      positively with Collaborating conflict style, Assertive Behavior, Influence, and
      Steadiness/Submissiveness but correlated negatively with Dominance personality
      domain, Passive, and Concealed Aggressive behaviors. CONCLUSION: EQ varied with
      level of training. EQ competence may occur by Collaborating and Assertive
      Behaviors utilizing Influence and Steadiness/Submissiveness personality domains.

PMID- 24937971
TI  - Serum human chorionic gonadotropin level measured 17 days after oocyte retrieval
      can predict final clinical pregnancy outcomes in IVF/ICSI treatment cycles.
AB  - OBJECTIVE: To investigate whether serum human chorionic gonadotropin (hCG) levels
      measured 17 days after oocyte retrieval can predict final clinical pregnancy
      outcomes in in vitro fertilization/intracytoplasmic sperm injection embryo
      transfer cycles. STUDY DESIGN: Serum hCG levels 17 days after oocyte retrieval
      and the subsequent clinical pregnancy outcomes in patients with positive serum
      hCG were analyzed. RESULTS: Of 6,560 patients, patients with positive but low
      serum hCG levels (< 100 IU/L) had an increased risk of abnormal clinical
      pregnancy outcomes (spontaneous miscarriage or ectopic pregnancy) (p < 0.05).
      Compared with abnormal clinical pregnancy, normal clinical pregnancy (live birth)
      showed significantly higher hCG levels at 17 days after oocyte retrieval (596.80
      IU/L vs. 277.80 IU/L, p < 0.001). The hCG level of live birth was markedly higher
      than that of spontaneous miscarriage (596.80 IU/L vs. 357.15 IU/L, p < 0.001) and
      ectopic pregnancy (596.80 IU/L vs. 129.30 IU/L, p < 0.001). The cutoff value was
      377.8 IU/L to predict live birth with 0.730 area under the receiver operating
      characteristic curve (95% CI 0.713-0.747, 75.9% sensitivity, 61.2% specificity, p
      < 0.001). CONCLUSION: Serum hCG levels measured on the 17th day after oocyte
      retrieval are clinically useful in predicting final clinical pregnancy outcomes.
      However, it is important to note that no hCG cutoff had a sensitivity or
      specificity of 100% for either normal or abnormal pregnancies, making it
      essential to continue routine monitoring of assisted reproductive technology
      pregnancy outcomes.

PMID- 24937972
TI  - Third trimester insulin levels are not correlated with fetal macrosomia or
      delivery complications.
AB  - OBJECTIVE: To examine the relationship of glucose and insulin levels during the 1
      hour gestational diabetes screening test to determine their relation to
      gestational diabetes mellitus (GDM) and possible resulting pregnancy
      complications. STUDY DESIGN: This is a prospective observational study of the
      delivery records of 784 patients who obtained third trimester screening for both
      glucose and insulin levels during routine 1-hour 50 g oral glucose load. RESULTS:
      Insulin levels were positively correlated with glucose levels (p < 0.001). GDM
      was diagnosed in 17 patients (2.2%). Mean birth weight was not significantly
      different with glucose levels < 130 pmol/L, 130-140 pmol/L, or > 140 pmol/L
      (3,282 g, 3,409 g, and 3,310 g, respectively, p = 0.13), nor were 5-minute Apgar
      scores (p = 0.66). No difference in mean fetal birth weight was found in insulin
      ranges < 30 pmol/L, 30-60 pmol/L, and > 60 pmol/L (3,330 g, 3,306 g, and 3,276 g,
      respectively, p = 0.56). Moreover, no significant differences in 5-minute Apgar
      scores were observed between those groups (p = 0.05). Women who underwent
      cesarean section (n = 230) had significantly higher glucose and insulin levels
      than did those who had vaginal deliveries (n = 554) (p = 0.01 and p = 0.003,
      respectively). CONCLUSION: Our data indicates that neither insulin nor glucose
      levels are predictive of fetal macrosomia, low Apgar scores, or birth injuries.

PMID- 24937973
TI  - Analysis of the safety and reliability of a hydrothermal ablation system: a
      multicenter, prospective postmarket study.
AB  - OBJECTIVE: To obtain information on practitioner experience in the use of the
      Genesys HydroThermAblator (HTA) System under normal clinical conditions through
      documentation of the system's acute safety features, in terms of burn rates, and
      its technical reliability. STUDY DESIGN: This was a prospective, observational,
      multicenter, postmarket interventional clinical trial with outcome measures of
      acute (within 21 days post-procedure) safety, serious adverse device effects, and
      technical malfunctions in a population of premenopausal women > or = 18 years of
      age. RESULTS: A total of 992 women (mean age, 41.7 +/- 6.8 years; range, 22-65
      years) were enrolled in 18 clinical sites throughout the United States. The
      Genesys HTA System provided low burn rates in the intent-to-treat (n = 992 [0.4%]
      [95% CI 0.1-1.0%]) and evaluable (n = 931 [0.2%] [95% CI 0.1-0.8%]) subject
      populations. Only 1 burn was clinically significant and was defined as a serious
      adverse device effect (1/992 [0.10%] [95% CI 0.0-0.6%]). Fifty-three (5.1%)
      technical malfunctions occurred in 44 procedures, and 27 (27/44 [61.4%]) patients
      completed their procedures after 31 (31/ 53 [58.5%]) technical problems were
      addressed and resolved. CONCLUSION: The Genesys HTA System delivers a safe and
      reliable treatment option for premenopausal women with heavy menstrual bleeding.

PMID- 24937974
TI  - Management of etonogestrel subdermal implant-related bleeding.
AB  - OBJECTIVE: To determine removal rates for unacceptable bleeding in etonogestrel
      subdermal implant (ESI) users treated with reassurance alone as well as in those
      receiving reassurance plus medical interventions including doxycycline and
      ibuprofen, and to compare removal rates between ESI users treated with
      reassurance alone with those receiving the medical interventions listed above in
      addition to reassurance. STUDY DESIGN: Medical records of 391 women receiving ESI
      for contraception within the period June 2007-April 2011 were abstracted for
      patient characteristics and interventions including reassurance, doxycycline, and
      ibuprofen. Removal rates were compared between intervention groups using the chi2
      test and multivariable logistic regression. RESULTS: Contact for bleeding
      occurred in 128 women (32.7%). Of those, 83 women (21.2% of entire cohort)
      requested removalfor bleeding (median, 381 days; range, 29-1,078 days). Of 53
      women receiving reassurance alone, 40 (75.5%) requested removal, whereas fewer
      (15 of 33 [45.5%]) women receiving reassurance plus doxycycline requested removal
      (p = 0.005), even after adjusting for prior contraception use and body mass index
      at ESI insertion (p = 0.006). Of 10 women receiving ibuprofen and 19 women
      receiving doxycycline plus ibuprofen, 7 (70.0%) and 11(57.9%), respectively,
      requested removal for bleeding. CONCLUSION: Reassurance plus doxycycline is
      associated with lower removal rates for ESI-related bleeding than is reassurance
      alone.

PMID- 24937975
TI  - Acupuncture performed before and after embryo transfer: a randomized controlled
      trial.
AB  - OBJECTIVE: To compare the clinical pregnancy rates in women who underwent fresh
      embryo transfer (ET) with and without one acupuncture session before and after
      the transfer using a modified Paulus protocol. STUDY DESIGN: The prospective,
      physician-blinded study randomized 113 women to either no intervention (n = 56)
      or acupuncture performed off-site (n = 57). Secondary outcomes were positive
      pregnancy test and live birth rates. Intent-to-treat analysis and per protocol
      analysis were performed. RESULTS: No difference in age and in vitro fertilization
      embryo transfer (IVF-ET) parameters were detected. Compared to the control group,
      the treatment group had a lower pregnancy rate (43.6% vs. 64.8%, p = 0.045). More
      women in the control group had live births than did those in the acupuncture
      group (56.0% vs. 36.0%, respectively, p = 0.033). Generalized mixed models
      revealed that patients who received acupuncture had lower odds of clinical
      pregnancy than those who did not undergo acupuncture treatment (OR = 0.42, 95% CI
      0.19-0.93). CONCLUSION: Our study found that acupuncture performed off-site on
      the day of ET was detrimental to the success of the transfer. More research is
      needed with a greater number of subjects to elucidate the role of acupuncture
      before and after ET, ideal treatment frequency, and to further explore the role
      of individualized acupuncture treatment on IVF-ET pregnancy rates.

PMID- 24937976
TI  - Does the addition of recombinant luteinizing hormone to progesterone for luteal
      supplementation improve IVF outcomes in high-responder patients? A preliminary
      randomized controlled study.
AB  - OBJECTIVE: To determine the impact of recombinant luteinizing hormone (rLH)
      combined with vaginal progesterone (P)for luteal supplementation on in vitro
      fertilization (IVF) pregnancy outcomes in high-responder patients undergoing long
      gonadotropin-releasing hormone (GnRH) agonist cycles. STUDY DESIGN: A total of 47
      patients undergoing IVF cycles with the serum estradiol levels of > or = 2,500
      pg/mL on the day of human chorionic gonadotropin administration were included in
      this prospective randomized study. Patients were divided into 2 treatment groups:
      the control group (n = 23) used luteal vaginal P, and the study group (n = 24)
      received a combination of vaginal P and 75 IU rLH, 4 doses every 3 days, starting
      on the day of embryo transfer. The main outcome measure was the clinical
      pregnancy rate (PR). RESULTS: The study group had 11 pregnancies (45.8%), while
      the control group had 6 (26.1%). There was no significant difference between the
      groups in clinical PRs (p = 0.15). No differences were found with respect to the
      implantation rate, miscarriage rate, and multiple PR. CONCLUSION: Our data show
      that luteal supplementation with rLH combined to vaginal P was not found to
      improve pregnancy outcomes in high responder patients undergoing long GnRH
      agonist IVF treatments.

PMID- 24937977
TI  - Anterior vaginal introitoplasty for an acquired sensation of wide vagina: a case
      report and new surgical intervention.
AB  - BACKGROUND: A vaginal introital defect case and its symptomatology have never
      been published before. The objective of this presentation was to describe
      symptoms associated with an acquired sensation of wide vagina and to present a
      new surgical treatment for anterior vaginal introital defects. CASE: A 42-year
      old, Caucasian woman, G4P4013, presented with a sensation of wide vagina at the
      vaginal opening and a history of colpoperineoplasty, without mesh, for the same
      condition 4 years prior. Clinical evaluation documented anterior vaginal
      introital defects and the absence of vaginal site-specific defects.
      Reconstruction of a vaginal introital defect was completed without complications.
      Surgical resolution of symptoms and signs of this condition were noted.
      CONCLUSION: Anterior vaginal introitoplasty can assist in the management of an
      acquired sensation of wide vagina.

PMID- 24937978
TI  - Clear cell adenocarcinoma of the abdominal wall: a case report.
AB  - BACKGROUND: Primary clear cell adenocarcinoma of the abdominal wall is
      exceptionally rare and most likely arises within scar endometriosis. CASE: A 37
      year-old woman with 3 prior cesarean sections developed an abdominal wall mass
      that was confirmed as clear cell adenocarcinoma. CONCLUSION: Clear cell
      adenocarcinoma is in the differential diagnosis of abdominal wall masses,
      particularly in cases of prior surgery. Fine needle aspiration may be helpful in
      establishing the diagnosis.

PMID- 24937979
TI  - May-Thurner syndrome complicating pregnancy: a report of four cases.
AB  - BACKGROUND: May-Thurner syndrome is a common anatomic variant associated with
      deep venous thrombosis. There are few reports describing implications for and
      management in pregnancy. CASES: We performed a retrospective review and
      description of 4 women with May-Thurner syndrome receiving complete or
      consultative obstetrical care in our practice. Presentations included (1)
      previous stroke from presumed paradoxical embolus, (2) chronic lower extremity
      venous congestion treated prepregnancy with stenting, (3) prior iliac thrombosis
      treated with thrombolysis, anticoagulation, and stenting, and (4) active third
      trimester iliac thrombosis. The first 3 patients received prophylactic
      anticoagulation, while the fourth was fully anticoagulated. CONCLUSION: May
      Thurner is an underappreciated cause of deep venous thrombosis in reproductive
      aged women. Awareness may lead to improved recognition, treatment, and fewer long
      term sequelae.

PMID- 24937980
TI  - Maldescended ovary associated with Mullerian and kidney dysgenesis: a case
      report.
AB  - BACKGROUND: Maldescended ovary is a rare entity which has been associated with
      Mullerian and kidney dysgenesis. It can be discovered incidentally during a
      workup for pelvic or abdominal pain or an infertility workup. While MRI is the
      best diagnostic tool for the discovery of this entity, it can also be discovered
      using pelvic or abdominal ultrasound or hysterosalpingogram or by diagnostic
      laparoscopy. CASE: We present a case of maldescended ovary associated with a
      unicornuate uterus, normal left ovary and fallopian tube, elongated right
      fallopian tube and utero-ovarian ligament, and right pelvic kidney, discovered
      incidentally during a workup for chronic pelvic and abdominal pain. CONCLUSION:
      It is important to consider looking for a maldescended ovary whenever a patient
      has a Mullerian and/or kidney anomaly with absence of one or both ovaries on
      pelvic imaging.

PMID- 24937981
TI  - Social media can strengthen emergency communication.

PMID- 24937982
TI  - Despite progress, more work still needed to prevent infections.

PMID- 24937983
TI  - Extending the reach of care: telehealth network provides services to rural areas.

PMID- 24937984
TI  - Speed to market: hospitals tap modular construction to meet building demand.

PMID- 24937985
TI  - Sustainable foundation: environmentally friendly flooring materials.

PMID- 24937986
TI  - Put it there: selecting attractive recycling stations.

PMID- 24937987
TI  - Light wave: energy savings, long life and quality of light drive LED adoption.

PMID- 24937988
TI  - ASHE provides answers to code questions.

PMID- 24937989
TI  - A dashboard for achieving ES excellence.

PMID- 24937990
TI  - Maintenance alternatives: CMS provides new options for taking care of equipment.

PMID- 24937991
TI  - Key leadership areas: how ES managers can achieve sustained success.

PMID- 24937992
TI  - Volunteerism & student leadership.

PMID- 24937993
TI  - Getting access for those in need.

PMID- 24937994
TI  - Team Rubicon.

PMID- 24937995
TI  - The personal side of student leadership.

PMID- 24937996
TI  - Happenings spotlight: student nurses step into action to support local VA
      initiative serving homeless veterans.

PMID- 24937997
TI  - We fix bullet holes.

PMID- 24937998
TI  - Credit bearing independent studies: translating leadership into scholarship.

PMID- 24938000
TI  - What does being an effective nurse leader mean to you? 2014 essay contest
      winners.

PMID- 24937999
TI  - Seeing is believing in a vision for the future.

PMID- 24938001
TI  - Shifting perspective.

PMID- 24938002
TI  - Many thanks to our volunteer leaders: these valuable individuals contribute much
      to ACHE, the profession.

PMID- 24938003
TI  - Financial planning in a value-based world.

PMID- 24938004
TI  - Quality, cost and accountable care.

PMID- 24938005
TI  - Decentralizing the pharmacy: baystate health improves patient safety while
      enhancing labor and inventory management efficiency.

PMID- 24938006
TI  - Innovation in healthcare.

PMID- 24938007
TI  - The ethics of hospital security: leaders have an ethical responsibility to ensure
      safety while maintaining organizational values.

PMID- 24938008
TI  - From ground zero to recovery: a hospital's devastating experience provides
      valuable lessons in hope and service.

PMID- 24938009
TI  - A holistic approach to health: focusing on social determinants promotes wellness
      and prevents disease.

PMID- 24938010
TI  - An ACA and delivery system reform update: a balanced scorecard analysis.

PMID- 24938011
TI  - High "ACHevers": postgraduate fellowships chart the course for early careerists.

PMID- 24938012
TI  - Helping boards achieve and demonstrate accountability: taking responsibility to
      new levels.

PMID- 24938013
TI  - Leading improvement in population health: focusing on population health requires
      a new leadership approach.

PMID- 24938014
TI  - Walking in physician shoes: empathy and communication are key to effective
      physician relations.

PMID- 24938015
TI  - Preface. Advances in clinical chemistry.

PMID- 24938016
TI  - Matrix metalloproteinases in coronary artery disease.
AB  - Matrix metalloproteinases (MMP) are a family of zinc-containing endoproteinases
      that degrade extracellular matrix (ECM) components. MMP have important roles in
      the development, physiology and pathology of cardiovascular system.
      Metalloproteases also play key roles in adverse cardiovascular remodeling,
      atherosclerotic plaque formation and plaque instability, vascular smooth muscle
      cell (SMC) migration and restenosis that lead to coronary artery disease (CAD),
      and progressive heart failure. The study of MMP in developing animal model
      cardiovascular systems has been helpful in deciphering numerous pathologic
      conditions in humans. Increased peripheral blood MMP-2 and MMP-9 in acute
      coronary syndrome (ACS) may be useful as noninvasive tests for detection of
      plaque vulnerability. MMP function can be modulated by certain pharmacological
      drugs that can be exploited for treatment of ACS. CAD is a polygenic disease and
      hundreds of genes contribute toward its predisposition. A large number of
      sequence variations in MMP genes have been identified. Case-control association
      studies have highlighted their potential association with CAD and its clinical
      manifestations. Although results thus far are inconsistent, meta-analysis has
      demonstrated that MMP-3 Glu45Lys and MMP-9 1562C/T gene polymorphisms were
      associated with CAD risk.

PMID- 24938017
TI  - Heat shock proteins and cardiovascular disease.
AB  - Atherosclerosis is the leading global cause of mortality, morbidity, and
      disability. Heat shock proteins (HSPs) are a highly conserved family of proteins
      with diverse functions expressed by all cells exposed to environmental stress.
      Studies have reported that several HSPs may be potential risk markers of
      atherosclerosis and related cardiovascular diseases, or may be directly involved
      in the atherogenic process itself. HSPs are expressed by cells in atherosclerotic
      plaque and anti-HSP has been reported to be increased in patients with vascular
      disease. Autoimmune responses may be generated against antigens present within
      the atherosclerotic plaque, including HSP and may lead to a cycle of ongoing
      vascular injury. It has been suggested that by inducing a state of tolerance to
      these antigens, the atherogenic process may be limited and thus provide a
      potential therapeutic approach. It has been suggested that anti-HSPs are
      independent predictors of risk of vascular disease. In this review, we summarize
      the current understanding of HSP in cardiovascular disease and highlight their
      potential role as diagnostic agents and therapeutic targets.

PMID- 24938019
TI  - Neutrophil gelatinase-associated lipocalin in cancer.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, is
      a 178-amino acid protein which exists in three molecular forms, including a 25
      kDa monomer, a 45-kDa homodimer, and a 135-kDa heterodimer complexed with matrix
      metalloproteinase 9 (MMP-9). Polymorphonuclear neutrophils and tubular cells of
      the kidney are the most representative cellular sources. As such, NGAL is now
      considered the biochemical gold standard for early diagnosis of acute kidney
      injury. Recent evidence suggests, however, that ectopic or enhanced expression of
      NGAL may occur in many other pathologic conditions including cancer. Several
      epidemiologic studies, as reviewed in this chapter, showed that a variety of
      malignant tumors consistently overexpressed NGAL with increased concentration in
      blood, urine, and other biologic fluids. In addition, NGAL was frequently
      associated with tumor size, stage, and invasiveness. These features thus make it
      a potential biomarker for malignancy. A number of experimental studies also
      demonstrated that the ability to bind MMP-9, to scavenge iron into cancer cells
      along with the effect on subcellular localization of transmembrane proteins such
      as cadherins and catenins, confers this protein the potential to enhance can cer
      aggressiveness and makes it an appealing target of future anticancer research.

PMID- 24938018
TI  - Apolipoprotein B-48: a unique marker of chylomicron metabolism.
AB  - Apolipoprotein B-48 (apoB-48) is known to be the only specific marker of
      intestinal chy lomicron particles. The amino acid sequence of apoB-48 represents
      48% of the initial sequence of apoB-100. ApoB-48 is synthesized only by the
      intestine in humans, while apoB-100 is synthesized primarily by the liver.
      Therefore, apoB-48 is a most appropriate biomarker for cardiovascular and
      nutritional investigation of postprandial chylomicron metabolism. In this review
      article, we discussed the difference between the recent find ings and
      Zilversmit's proposal of postprandial hyperlipidemia reported over 30 years ago.
      The characteristics and role of apoB-48 as an apolipoprotein in chylomicrons,
      especially as a marker of chylomicron remnant lipoproteins, are described. The
      need for appropriate analytical methods to measure apoB-48 is also discussed.

PMID- 24938020
TI  - Autoantibodies in breast cancer.
AB  - In addition to their historical role, autoantibodies appear promising as
      biomarkers to facilitate diagnosis, improve patient outcome and decrease
      mortality in cancer. Autoantibodies may also be useful in the identification of
      subjects at risk for cancer, that is, those bearing premalignant changes.
      Numerous studies have demonstrated that cancer serum contains a variety of
      autoantibodies that react with autologous cellular antigens, that is, tumor
      associated antigens. Interestingly, some of these antigens are involved in signal
      transduction, cell cycle regulation, cell proliferation, and apoptosis. As such,
      identification of these molecules has additional importance for development of
      novel anticancer drugs and vaccines. This review focuses on the use of
      autoantibodies in breast cancer, a major public health problem. We also address
      the need for additional research to validate this approach in cancer diagnostics
      and therapeutics in general.

PMID- 24938021
TI  - Mammaglobin A: review and clinical utility.
AB  - Mammaglobin A is a protein that belongs to the secretoglobin superfamily. It has
      highly specific expression in cells from most breast cancers and may be used to
      detect circulating or disseminated tumor cells. In addition, mammaglobin A is
      currently under inves tigation as a potential therapeutic target for immune
      therapies that target breast cancer. The present review will highlight our
      current understanding of mammaglobin A at the genetic and protein level and its
      potential clinical applications. Characteristics of breast cancer and methods
      used to isolate and detect circulating tumor cells will also be presented.

PMID- 24938022
TI  - 1,5-Anhydroglucitol and glycated albumin in glycemia.
AB  - The main purpose of treating diabetes is to prevent the onset and the progression
      of diabetic chronic complications. Since the mechanism of onset of chronic
      complications is still not well understood, the main strategy to achieve this
      purpose is to bring the plasma glucose level in diabetic patients as close as
      possible to that in healthy subjects and try to maintain good glycemic control
      over the long term. Glycated hemoglobin (HbA1c), glycated albumin (GA),
      fructosamine, and 1,5-anhydroglucitol (1,5 AG) are used for evaluating glycemic
      control. At present, HbA1c is widely used as a gold standard index for glycemic
      control in clinical practice. While HbA1c reflects the long-term glycemic control
      state (for the past 1-2 months), it does not accurately reflect glycemic control
      in the clinical state in which glycemic control improves or deteriorates in the
      short-term. It is also known that HbA1c in patients with hematological disorders
      such as anemia and variant hemoglobin shows an abnormal value. In addition, HbA1c
      mainly reflects the mean plasma glucose but does not reflect the postprandial
      plasma glucose. On the other hand, GA and 1,5-AG reflect intermediate- or short
      term glycemic control and are not influenced by hemoglobin metabolism. While 1,5
      AG is known to reflect the postprandial plasma glucose, it was shown recently
      that GA also reflects the postprandial plasma glucose. This chapter summarizes
      the measurement methods, usage methods, evidence, and problems concerning such
      indices for glycemic control.

PMID- 24938023
TI  - Management innovation from HMA.

PMID- 24938024
TI  - Building a culture for innovation: a leadership challenge.
AB  - It is recognized that health services are facing increasing cost pressures amid a
      climate of increasing demand and increasing expectations from patients and
      families. The ability to innovate is important for the future success of all
      health care organizations. By malting some simple but profound changes in
      behaviours and processes as illustrated across seven dimensions, leaders can have
      great impact on the culture for innovation. This in turn can support the
      transformation of health services through increased innovation.

PMID- 24938025
TI  - The key to health services in Turkey: new perspectives on leadership and hospital
      management.
AB  - Health services are one of the most important criteria for making a country
      function. Turkey has mobilized all of its resources to provide high-quality,
      easily accessible and patient-friendly services for its population. To achieve
      this aim, the Turkish health care system has been undergoing a significant
      transformation through its Health Transformation Programme begun in 2005. The
      reforms focus on the introduction of a general health insurance system, changing
      hospital health services, improvements in hospital management and
      transformational leadership skills. Firstly, all state-run hospitals in the
      country were merged under the same umbrella, giving millions of people covered by
      the national security agency access to all of these hospitals. Secondly, all
      drugs and medical equipment used by patients were made free of charge. Thanks to
      these developments, hospitals were modernized, and this modernization process in
      the health sector is still continuing swiftly. On the other hand, for Turkish
      hospitals to survive, they need to modernize further and become closer to
      European models, and produce new leaders with new paradigms. In this new and
      changing health system, hospital leaders and executive officers should be
      visionaries and strategists advising when to change direction. Following this
      doctrine, most Turkish hospitals are now run by two top executives: the hospital
      manager and the chief executive officer who is in charge of business functions.
      These executives should clearly be the leaders of high-quality, health care
      organizations.

PMID- 24938026
TI  - The National Accreditation Board for Hospital and Health Care Providers
      accreditation programme in India.
AB  - Quality in health care is important as it is directly linked with patient safety.
      Quality as we know is driven either by regulation or by market demand. Regulation
      in most developing countries has not been effective, as there is shortage of
      health care providers and governments have to be flexible. In such circumstances,
      quality has taken a back seat. Accreditation symbolizes the framework for quality
      governance of a hospital and is based on optimum standards. Not only is India
      establishing numerous state of the art hospitals, but they are also experiencing
      an increase in demand for quality as well as medical tourism. India launched its
      own accreditation system in 2006, conforming to standards accredited by ISQua.
      This article shows the journey to accreditation in India and describes the
      problems encountered by hospitals as well as the benefits it has generated for
      the industry and patients.

PMID- 24938027
TI  - Hospital accreditation--a foundation for high reliability.
AB  - The people who work in health care organizations are committed to providing the
      best care possible to their patients. In the contemporary health care environment
      this is a very difficult commitment to keep. Health care has never been more
      complicated or demanding of the people who work in the industry. This article
      describes two different but complimentary methods for improving the quality and
      safety of health care. Accreditation provides a foundation for creating systems
      of care across many types of health care organizations. High reliability inspires
      people and organizations to strive for the highest levels of performance.
      Together, these methods give people working in health care an opportunity to
      fulfil their commitment to their patients.

PMID- 24938028
TI  - Hospital productivity: how to KILL or create a productive hospital environment.
AB  - Productivity is NOT the same as quality. Productivity is about the value-add we
      bring to work, to each job, to each day. To create a productive hospital
      environment, it is so much more than buying the right equipment or hiring the
      right mix of people. Productivity comes from investing in our people and giving
      them the tools and authority to do their jobs effectively. Adding more "quality
      programmes" can actually kill productivity by taking people away from their core
      jobs. Adding a tick-list in the operating theatre can cut mortality rates in half
      by eliminating the smallest of mistakes. This article is a guide to help you
      focus on the key elements of productivity and not to get distracted by the hype
      and confusion from media. Its bottom-line focus and "how-to" tools and ideas make
      it useful and practical.

PMID- 24938029
TI  - Teamwork and communication: an effective approach to patient safety.
AB  - Teamwork and communication failures are leading causes of patient safety
      incidents in health care. Though health care providers must work in teams, they
      are not well-trained in teamwork and communication skills. Health care faces the
      problems of differences in communication styles, communication failures and poor
      teamwork. There is enough evidence in the literature to show that communication
      failure is detrimental to patient safety. It is estimated that 80% of serious
      medical errors worldwide take place because of miscommunication between medical
      providers. NUH recognizes that effective communication and teamwork are essential
      in the delivery of high quality safe patient care, especially in a complex
      organization. NUH is a good example, where there is a rich mix of nationalities
      and races, in staff and in patients, and there is a rapidly expanding care
      environment. NUH had to overcome these challenges by adopting a multi-pronged
      approach. The trials and tribulations of NUH in this journey were worthwhile as
      the patient safety climate survey scores improved over the years.

PMID- 24938030
TI  - Are clinical audits enough to bring about improvement in overall health care
      delivery?
AB  - This study was conducted to explore the entire spectrum of initiatives that have
      evolved globally over time in health care delivery mechanisms. The quality
      improvement initiatives that have been reviewed were undertaken at the department
      of radiology at a tertiary care teaching hospital in the developing world. This
      article reveals that conducting only clinical audits is not enough to bring about
      improvements in the health care delivery processes. It also illustrates examples
      of other initiatives that combine to enable sustainable, safe and high quality
      health care services for the patients whom we serve.

PMID- 24938031
TI  - Assessment of changes in health care needs.
AB  - By 2020, the population of Ulaanbaatar will reach 1,522,400 inhabitants. In
      addition, estimates show that relative to 2010, there will be 13.1% more
      outpatient registrations and 11.6% more inpatients by 2020. This study, conducted
      by descriptive design based on demographic and morbidity data, analyzes whether
      current health care facilities meet the demands and needs of the Ulaanbaatar
      population. It also assesses health care needs and accessibilty in Ulaanbaatar by
      2020. Both data analysis and qualitative interviews with different sub-groups of
      the population reveal the neccesity to both reorganize primary level health care
      facilities and adjust resources in accordance with changing morbidity patterns.

PMID- 24938032
TI  - Adapt or disappear: AHMA's reality 2016 has a new mission to transform the HIM
      workforce through education-- or else.

PMID- 24938033
TI  - Evolving ROI specialists into health record ambassadors.

PMID- 24938034
TI  - Weaving together a healthcare improvement tapestry. Learning health system brings
      together health data stakeholders to share knowledge and improve health.

PMID- 24938035
TI  - Paging Dr. Watson: IBM's Watson supercomputer now being used in healthcare.

PMID- 24938036
TI  - Black market PHI does exist: why it's time to take security risk assessments
      seriously.

PMID- 24938037
TI  - The role of analyzing healthcare data: health data analysts aggregate, evaluate,
      and validate information for key healthcare stakeholders.

PMID- 24938038
TI  - Too many coding systems, too much to do: different clinical classification and
      clinical terminology systems uniquely impact IT, quality management.

PMID- 24938039
TI  - Researchers using visual analytics to improve care quality.

PMID- 24938040
TI  - Managing the integrity of patient identity in health information exchange
      (updated).

PMID- 24938041
TI  - Coding breast procedures with CPT.

PMID- 24938042
TI  - Coding ICD-10-PCS medical and surgical-related sections: understanding
      measurement and monitoring, extracorporeal assistance and performance, and
      extracorporeal therapies.

PMID- 24938043
TI  - [Two level thrombosis. Mysterious bruises on the leg. Hemorrhage in preexisting
      hematoma].

PMID- 24938044
TI  - [Circus-like acrobatics in the snow. Snowboard: fun with high accident risk].

PMID- 24938045
TI  - [General practice report. Giving wings to desire to travel].

PMID- 24938046
TI  - [Police overpowers aggressive patient].

PMID- 24938047
TI  - [Electronic medical record. Fiction of a safe digital identity in health care].

PMID- 24938048
TI  - [Not too much and not too little. How much sleep is optimal?].

PMID- 24938049
TI  - [Good sleep promotes retention. Learning overnight].

PMID- 24938050
TI  - [Music and relaxation promotion brain development of the fetus. Better dreams in
      the uterus].

PMID- 24938051
TI  - [New EULAR recommendations on rheumatoid arthritis and cortisone. Patient treated
      with high dose cortisone: what must be considered?].

PMID- 24938052
TI  - [Opioid lozenges, sprays, injections. Control of breakthrough pain].

PMID- 24938053
TI  - [Switching to vitamin K antagonists. More strokes during the first week?].

PMID- 24938055
TI  - [Stubborn urticaria: is there an alternative to cortisone?].

PMID- 24938054
TI  - [Naturopathy consultation. Soon all patients will be curable. Decisive
      breakthrough in therapy of hepatitis C ].

PMID- 24938056
TI  - [Survival time of chocolate in hospital departments].

PMID- 24938057
TI  - [Virgin births still happen today].

PMID- 24938058
TI  - [10 ground rules to observe in disposal of surgical instruments].

PMID- 24938059
TI  - [Shaken, not stirred: did James Bond have an alcohol problem?].

PMID- 24938060
TI  - [Baby boom after championship league victory?].

PMID- 24938061
TI  - [Nasal polyps, sialolithiasis, oropharyngeal cancer. Otolaryngology: exciting
      like a thriller].

PMID- 24938062
TI  - [Nasal polyps--what the general practitioner should know].

PMID- 24938063
TI  - [Sialolithiasis].

PMID- 24938064
TI  - [Oropharyngeal squamous cell cancer--change in pathogenesis].

PMID- 24938065
TI  - [Emergency checklist: rupture of the quadriceps tendon].

PMID- 24938066
TI  - [After-care in general practice after tick-borne encephalitis].

PMID- 24938068
TI  - [Proctological complaints: how helpful are anal hygiene, dieting and topical
      therapy?].

PMID- 24938067
TI  - [Iron deficiency anaemia].

PMID- 24938069
TI  - [Sudden rise in liver transaminase activities].

PMID- 24938070
TI  - [Intestine specific broad spectrum antibiotic. Rifaximin: therapy option in
      hepatic encephalopathy].

PMID- 24938071
TI  - [Industry and product information. Retaining an overview with e-college].

PMID- 24938072
TI  - Anxiety has a survival value to an animal under threat.

PMID- 24938073
TI  - Therapeutic applications of hypnosis.

PMID- 24938074
TI  - Placebo, hypnosis, and antidepressants: who is wearing the emperor's new clothes?

PMID- 24938075
TI  - Hypnotherapeutic treatment for anxiety-related relational discord: a short-term
      hypnotherapeutic protocol.
AB  - Hypnotherapeutic interventions are currently used to treat both anxiety disorders
      and relational discord between couples, yet few hypnotherapeutic interventions
      specifically address anxiety disorders within the context of a romantic
      partnership. This article explores a short-term hypnotherapeutic treatment
      protocol designed for couples' therapy in which the relational dynamic has been
      impacted by one partner's anxiety disorder. Anxiety not only causes suffering for
      the anxious patient, but can negatively impact intimate relationships as well.
      The hypnotherapeutic treatment protocol advanced in this article is specifically
      designed to address relational discord which is fueled by the presence of one
      partner's anxiety, and complements more standard individual treatment for anxiety
      disorders. Strategies to assess for the presence of relational discord with
      individual patients presenting with an anxiety disorder are included, as well as
      implications for longer-term couples' treatment.

PMID- 24938076
TI  - Childhood anxiety and psychophysiological reactivity: hypnosis to build
      discrimination and self-regulation skills.
AB  - Clinically anxious, worried, and fearful children and teens need clinicians'
      assistance in reducing their exaggerated psychophysiological stress reactivity.
      Affective neuroscience finds that chronic activation of the body's emergency
      response system inhibits neurogenesis, disrupts neuronal plasticity, and is
      detrimental to physical and mental health. Patterns of faulty discrimination
      skills, for example, over-estimation of threat and danger and under-estimation of
      their coping capacity, fuel this over-arousal. Similarly, contributory patterns
      of reduced self-regulation skills are shown by "stuck" attention to and poor
      control of their exaggerated psychophysiological reactivity and somatization.
      This article considers the literature and focuses on cognitive hypnotherapy to
      enhance these under-developed capacities. A case illustration highlights various
      hypnotic phenomena and techniques, psychoeducation, and relaxation training that
      address the goals of interrupting these unproductive, interconnected patterns and
      fostering new patterns of more realistic and accurate discrimination capacities
      and sturdier psychophysiological self-regulation skills.

PMID- 24938077
TI  - The wounded self: new approach to understanding and treating anxiety disorders.
AB  - This article synthesizes the concept of "wounded self" in the understanding and
      psychological treatment of anxiety disorders. The focal point of this concept is
      the notion of self-wounds or early unresolved emotional injuries. According to
      this conceptualization, anxiety represents an unconscious fear of unbearable
      insult to the wounded self, which is protected by maladaptive conscious
      strategies such as avoidance, cognitive distortions, or emotional constriction.
      This perspective provides a theoretical basis for blending elements of
      psychodynamic, behavioral, cognitive, and experiential therapies in the
      psychological management of anxiety disorders. As cognitive hypnotherapy embodies
      all of these therapeutic elements, its application to anxiety disorders is
      described in this article. Various hypnotherapeutic techniques for symptomatic
      relief and for eliciting and healing the wounded self are discussed and
      exemplified by a case. This case illustrates that symptom-focused treatment is
      necessary, but not sufficient. A more durable treatment requires resolution of
      underlying conflicts that drive the anxiety.

PMID- 24938078
TI  - Current issues in the treatment of specific phobia: recommendations for
      innovative applications of hypnosis.
AB  - Specific phobia is the most common and treatable of the anxiety disorders.
      Exposure-based therapies are the treatment of choice and empirically validated
      protocols are available that promise rapid and effective results. In many cases,
      however, patients are reluctant to comply with demanding schedules of exposure,
      increasing the risk of treatment failure. Furthermore, in clinical practice,
      patients often present with multiple phobias and other Axis I and Axis II
      disorders that can further complicate therapy. This article covers four important
      issues that have been addressed in the literature: (a) managing resistance to
      treatment, (b) reducing length of treatment, (c) clarifying the optimal
      application of relaxation training, and (d) applying advances in cognitive
      neuroscience. These issues are reviewed and recommendations proposed for ways in
      which to modify current treatments. Specific suggestions are provided for
      implementing these recommendations including examples of innovative applications
      of standard hypnotic techniques.

PMID- 24938079
TI  - Hypnosis aided fixed role therapy for social phobia: a case report.
AB  - This case study details how hypnosis aided fixed role therapy (HAFRT) was
      employed in the successful treatment of a case of social phobia with a history of
      refractory outcomes to previous therapy trials. The treatment consisted of 10
      office sessions, scheduled every two weeks, of HAFRT along with twice a day self
      hypnotic sessions where the patient performed multiple visualization rehearsals
      of the vignettes that were successfully mastered in hypnosis during office
      visits. The results indicated that this patient was able to engage in social and
      professional affairs that were impossible prior to treatment. The patient
      retained the therapy gains at follow up 6 months later.

PMID- 24938080
TI  - Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with
      colon cancer were associated with worse survival.
AB  - BACKGROUND: The influence of natural regulatory T cells (nTregs) on the patients
      with colon cancer is unclear. Demethylated status of the Treg-specific
      demethylated region (TSDR) of the FOXP3 gene was reported to be a potential
      biomarker for the identification of nTregs. METHODS: The demethylation rate of
      the TSDR (TSDR-DMR) was calculated by using methylation-specific quantitative
      polymerase chain reaction (MS-qPCR) assay. The expression of TSDR-DMR and FOXP3
      mRNA was investigated in various colorectal cancer cell lines. A total of 130
      colon carcinoma samples were utilized to study the DMR at tumor sites (DMRT) and
      adjacent normal tissue (DMRN). The correlations between DMRs and
      clinicopathological variables of patients with colon cancer were studied.
      RESULTS: The TSDR-DMRs varied dramatically among nTregs (97.920 +/- 0.466%) and
      iTregs (3.917 +/- 0.750%). Significantly, DMRT (3.296 +/- 0.213%) was higher than
      DMRN (1.605 +/- 0.146%) (n = 130, p = 0.000). Higher DMRN levels were found in
      female patients (p = 0.001) and those with distant metastases (p = 0.017), and
      were also associated with worse recurrence-free survival in non-stage IV patients
      (low vs. high, p = 0.022). However, further Cox multivariate analysis revealed
      that the FOXP3-TSDR status does not have prognostic value. CONCLUSION: MS-qPCR
      assays of FOXP3-TSDR can efficiently distinguish nTregs from non-nTregs. Abnormal
      recruitment of nTregs occurs in the local tumor microenvironment. Infiltration of
      tissue-resident nTregs may have a negative role in anti-tumor effects in patients
      with colon cancer; however, this role is limited and complicated.

PMID- 24938082
TI  - Smart core-shell microgel support for acetyl coenzyme A synthetase: a step toward
      efficient synthesis of polyketide-based drugs.
AB  - The flexibility in tuning the structure and charge properties of PNIPAm microgels
      during their synthesis makes them a suitable choice for various biological
      applications. Two-step free radical polymerization, a common method employed for
      synthesis of core-shell microgel has been well adopted to obtain cationic poly(N
      isopropylacrylamide-aminoethyl methacrylate) (PNIPAm-AEMA) shell and PNIPAm core.
      Scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta
      potential, and ninhydrin assay suggests nearly monodispersed particles of
      cationic nature. Amino groups on the microgel provides suitable attachment point
      for covalent immobilization of acetyl coenzyme A synthetase (Acs) via 1-ethyl-3
      (3-N,N- dimethylaminopropyl) carbodiimide (EDC) chemistry. On immobilization,
      61.55% of initial activity of Acs has been retained, while Michaelis-Menten
      kinetics of the immobilized Acs indicates identical K(m) (Michaelis constant) but
      decrease in the V(max) (maximum substrate conversion rate) compared to free
      enzyme. Immobilized Acs shows an improvement in activity at wide temperature and
      pH range and also demonstrates good thermal, storage, and operational stability.
      The Acs-microgel bioconjugate has been successfully reused for four consecutive
      operation cycles with more than 50% initial activity.

PMID- 24938081
TI  - The efficacy of a behavioral activation intervention among depressed US Latinos
      with limited English language proficiency: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Major depressive disorder is highly prevalent among Latinos with
      limited English language proficiency in the United States. Although major
      depressive disorder is highly treatable, barriers to depression treatment have
      historically prevented Latinos with limited English language proficiency from
      accessing effective interventions. The project seeks to evaluate the efficacy of
      behavioral activation treatment for depression, an empirically supported
      treatment for depression, as an intervention that may address some of the
      disparities surrounding the receipt of efficacious mental health care for this
      population. METHODS/DESIGN: Following a pilot study of behavioral activation
      treatment for depression with 10 participants which yielded very promising
      results, the current study is a randomized control trial testing behavioral
      activation treatment for depression versus a supportive counseling treatment for
      depression. We are in the process of recruiting 60 Latinos with limited English
      language proficiency meeting criteria for major depressive disorder according to
      the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for
      participation in a single-center efficacy trial. Participants are randomized to
      receive 10 sessions of behavioral activation treatment for depression (n = 30) or
      10 sessions of supportive counseling (n = 30). Assessments occur prior to each
      session and at 1 month after completing treatment. Intervention targets include
      depressive symptomatology and the proposed mechanisms of behavioral activation
      treatment for depression: activity level and environmental reward. We will also
      examine other factors related to treatment outcome such as treatment adherence,
      treatment satisfaction, and therapeutic alliance. DISCUSSION: This randomized
      controlled trial will allow us to determine the efficacy of behavioral activation
      treatment for depression in a fast-growing, yet highly underserved population in
      US mental health services. The study is also among the first to examine the
      effect of the proposed mechanisms of change of behavioral activation treatment
      for depression (that is, activity level and environmental reward) on depression
      over time. To our knowledge, this is the first randomized controlled trial to
      compare an empirical-supported treatment to a control supportive counseling
      condition in a sample of depressed, Spanish-speaking Latinos in the United
      States. TRIAL REGISTRATION: Clinical Trials Register: NCT01958840; registered 8
      October 2013.

PMID- 24938083
TI  - Complete mitochondrial genome of Sipunculus nudus (Sipuncula, Sipunculidae).
AB  - In this paper, the complete mitochondrial (mt) genome of Sipunculus nudus
      collected from the coast of southeast China was determined. The complete mt
      genome was 15,376 bp in length, including 13 protein-coding genes, 2 rRNA genes,
      23 tRNA genes, and a putative control region (CR). The overall base composition
      of the H-strand is 29.25% A, 28.78% T, 27.19% C, and 14.78% G, with an AT content
      of 58.03%. The mt DNA of Chinese S. nudus shared 73.6% and 60.2% identities with
      that of French S. nudus (GenBank accession number: FJ42,2961) and Chinese
      Phascolosoma esculenta (GenBank accession number: EF58,3817), respectively. 

PMID- 24938084
TI  - Complete mitochondrial genome of Sakhalin taimen Parahucho perryi (Salmoniformes,
      Salmonidae) without two frame-disrupting indels in the ND4 gene.
AB  - The complete mitochondrial genome was sequenced in two individuals of Sakhalin
      taimen Parahucho perryi. The genome sizes were 16,652 bp and 16,653 bp in the two
      isolates. Gene arrangement, base composition, and size of the two sequenced
      haplotypes are very similar to the P. perryi genome previously published
      (KC897653), but do not contain two frame-disrupting indels in the ND4 gene. 

PMID- 24938085
TI  - Complete mitochondrial genome of the green odorous frog Odorrana margaretae
      (Anura: Ranidae).
AB  - The complete mitochondrial genome (mitogenome) of the green odorous frog Odorrana
      margaretae (Anura: Ranidae) has been studied. The 17,903 bp circular genome
      contains the typical complement of 13 protein-coding genes, 2 ribosomal RNAs, 22
      transfer RNAs, and a control region. The AT content of the overall base
      compositon of H-strand is 56% and the length of control region is 2501 bp with
      63.8% AT content. The arrangement of the protein-coding and ribosomal RNA genes
      was the same as that found in other anurans. The cluster of rearranged LTPF tRNA
      genes and the translocation of tRNA(His) gene into the D-loop region are
      observed. 

PMID- 24938086
TI  - Complete mitochondrial genome of the sixblotch hind Cephalopholis sexmaculata
      (Pisces: Perciformes).
AB  - The complete mitogenome of the sixblotch hind, Cephalopholis sexmaculata was
      presented in this study. This mitochondrial genome consists of 16,589 bp, with 13
      protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a
      noncoding control region (CR), and its gene arrangement is identical to most
      vertebrates. The overall base composition of the heavy strand is A, 29.35%; G,
      16.08%; C, 28.56%; and T, 26.01%. The COI gene started with GTG codon and the
      ATP6 gene started with CTG codon. The complete mitogenomic data may provide
      informative for further phylogenetic approach of species of Cephalopholis and
      related genera belong to the Epinephelidae groupers. 

PMID- 24938087
TI  - The complete mitochondrial genome of the invasive house crow Corvus splendens
      (Passeriformes: Corvidae).
AB  - The complete mitochondrial genome of the invasive house crow (Corvus splendens)
      was sequenced (GenBank accession number: KJ766304) using the MiSeq Personal
      Sequencer (Illumina, San Diego, CA). The mitochondrial genome is 16,962 bp in
      length, comprising 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal
      subunit genes and a non-coding control region. The mitogenome structural
      organization is identical to that of the other Corvus species and related genera.
      The overall base composition of C. splendens is 30.65% for A, 29.71% for C,
      14.84% for G and 24.80% for T, with an AT content of 55.45%. We propose to use
      full mitochondrial genome to address taxonomic issues and to study the population
      genetics of crows. 

PMID- 24938088
TI  - The complete mitochondrial genome of an agama, Phrynocephalus putjatia (Reptilia,
      Squamata, Agamidae).
AB  - The complete mitochondrial genome was sequenced from the toad-headed viviparous
      lizard, Phrynocephalus putjatia. The mitogenome was 16,283 bp in length; it
      contained 13 protein coding, 22 tRNA, 2 rRNA genes and 2 control regions. The
      gene order and compositions were identical with all published congeneric
      mitogenomes for the fragment between 12 s RNA and tRNA-Thr, but with some
      differences for the remaining sequences including CR, tRNA-Pro and tRNA-Phe. The
      characteristics of the mitogenome was analyzed and discussed in detail. 

PMID- 24938089
TI  - The complete mitochondrial genome of the sandbar shark Carcharhinus plumbeus.
AB  - The sandbar shark, Carcharhinus plumbeus, a major representative species in shark
      fisheries worldwide is now considered vulnerable to overfishing. A pool of
      774,234 Roche 454 shotgun sequences from one individual were assembled into a
      16,706 bp mitogenome with 33* average coverage depth. It comprised 13 protein
      coding genes, 22 transfer RNA's, 2 ribosomal genes and 2 non-coding regions,
      typical of a vertebrate mitogenome. As expected for sharks, an A-T nucleotide
      bias was evident. This adds to rapidly growing number of mitogenome assemblies
      for the economically important Carcharhinidae family. The C. plumbeus mitogenome
      will assist researchers, fisheries and conservation managers interested in shark
      molecular systematics, phylogeography, conservation genetics, population and
      stock structure. 

PMID- 24938090
TI  - DNA barcoding and phylogenetic relationships in Anatidae.
AB  - Mitochondrial cytochrome c oxidase subunit I (COI) has been used as a powerful
      marker in a variety of phylogenetic studies. According to studies of bird
      species, the 694-bp sequence of the mitochondrial gene encoding COI is extremely
      useful for species identification and phylogeny. In the present study, we
      analyzed the COI barcodes of 79 species from 26 genera belonging to the Anatidae
      family. Sixty-six species (83.54%) of the species were identified correctly from
      their DNA barcodes. The remaining 13 species shared barcodes sequences with
      closely related species. Kimura two-parameter (K2P) distances were calculated
      between barcodes. The average genetic distance between species was 41 times
      higher compared to the average genetic distance within species. Neighbor-joining
      method was used to construct a phylogenetic tree, which grouped all of the genera
      into three divergent clades. Dendrocygna and Nomonyx + Oxyura were identified as
      early offshoots of the Anatidae. All the remaining taxa fell into two clades that
      correspond to the two subfamilies Anserinae and Anatiane. Based on our results,
      DNA barcoding is an effective molecular tool for Anatidae species identification
      and phylogenetic inference. 

PMID- 24938091
TI  - Complete mitochondrial genome of disc coral Turbinaria peltata (Scleractinia,
      Dendrophylliidae).
AB  - To date, no complete nucleotide sequences of the mitochondrial genome of
      Dendrophylliidae are yet available. In our study, the entire mitochondrial
      nucleotide sequence was determined for the Dendrophylliidae species Turbinaria
      peltata. The sequence was 18,966 bp in length and contained thirteen protein
      coding genes, two ribosomal RNA genes (12S rRNA and 16S rRNA), two transfer RNA
      genes (tRNA(Met) and tRNA(Trp)) and a putative control region locating between
      Cyt b and ND2. The overall base composition of the mitogenome was 25.6% A, 37.4%
      T, 23.5% G, and 13.5% C, with a high AT content of 63%, indicating an obvious
      anti-guanine bias. It shared 93.7%, 87% and 84.8 % mitogenome sequence with
      Goniopora columna, Acropora robusta and Euphyllia ancora, respectively. 

PMID- 24938092
TI  - Complete mitochondrial genome of Platevindex sp. (Gastropoda: Pulmonata:
      Systellommatophora: Onchidiidae).
AB  - The complete mitochondrial genome sequence of Platevindex sp. is firstly
      described in the article. The mitogenome (13,908 bp) contains 22 tRNA genes, 2
      ribosomal RNA genes and 13 protein-coding genes, and 1 putative control region
      (CR). CR is not well characterized due to lack of discrete conserved sequence
      blocks. This characteristic is similar with CRs of other invertebrate
      mitochondrial genomes. The characteristic is the typical bivalvia mitochondrial
      gene composition. 

PMID- 24938093
TI  - Extreme sequence divergence between mitochondrial genomes of two subspecies of
      White-breasted Wood-wren (Henicorhina leucosticta, Cabanis, 1847) from western
      and central Panama.
AB  - Prior studies of mitochondrial variation in White-breasted Wood-Wrens
      (Henicorhina leucosticta) have suggested that populations in South American and
      Mesoamerica might represent multiple species. Here we report the complete
      mitochondrial genomes from two individuals of H. leucosticta, representing the
      Panamanian subspecies pittieri and alexandri. The two sequences were 16,721 and
      16,726 base pairs in size with both genomes comprised of the usual 22 tRNA genes,
      2 rRNA genes, 13 protein-coding genes, and one displacement loop region in the
      standard avian order. Uncorrected pairwise divergence between mitogenome features
      was high, with the highest divergence occurring in protein-coding genes (average
      = 8.2%), followed by control region (6.7%). RNA features had lower pairwise
      divergences (average tRNA = 4.3%, average rRNA = 2.3%). The protein-coding ATPase
      6 gene had a different stop codon between these two specimens. The high level of
      sequence variation between these subspecies suggests that Mesoamerican H.
      leucosticta might be comprised of multiple species. We urge a full
      phylogeographic survey of this widespread Neotropical forest bird.

PMID- 24938094
TI  - Determination and analysis of the complete mitochondrial genome sequence of
      Yanling white goose.
AB  - In this study, the complete mitochondrial genome sequence of the Yanling white
      goose was reported in Human Province first, which was determined through PCR
      based method. The total length of the mitogenome is 16,742 bp. It contains the
      typical structure, including 2 ribosomal RNA genes, 22 transfer RNA genes, 13
      protein-coding genes and 1 non-coding control region (D-loop region) as that of
      most other vertebrates. The overall composition of the mitogenome was estimated
      to be 30.22% for A, 22.70% for T, 32.02% for C and 15.07% for G. All the protein
      initiation codons are ATG, except for COX1, COX2 and ND5 are GTG, ND6 is CTA. The
      complete mitochondrial genome sequence of the Yanling white goose in Human
      Province provides an important data set for the study in genetic mechanism of
      poultry. 

PMID- 24938095
TI  - Molecular characterization of sympatrically distributed Neotricula aperta-like
      snails in the Mekong River, Kratie, Cambodia.
AB  - Fifty-six samples of Neotricula aperta-like snails were collected from six
      locations in Cambodia. Their mitochondrial cytochrome c oxidase subunit 1 (cox1)
      sequences were examined using haplotype network and neighbor-joining (NJ) tree
      analysis. Twenty-seven haplotypes (H1-H27) were observed and were divided into
      two different groups/lineages. Of 27, 17 haplotypes (H11-H27) were clustered with
      the reference samples of the gamma-race N. aperta. The remaining 10 haplotypes
      (H1-H10) were clustered in a separate group/lineage, differing from the reference
      samples of the alpha-, beta-, and gamma-race N. aperta, suggesting a new lineage
      belonging the genus Neotricula. Our results show that both the gamma-race and a
      new lineage were sympatrically present approximately 60 km upstream of the Mekong
      River near the Kratie port, Cambodia. Further morphological and molecular studies
      are required to confirm the taxonomic status of this new, unidentified lineage. 

PMID- 24938096
TI  - The complete mitochondrial genome of the American black flour beetle Tribolium
      audax (Coleoptera: Tenebrionidae).
AB  - Flour beetles of the genus Tribolium are all pests of stored products and cause
      severe economic losses every year. The American black flour beetle Tribolium
      audax is one of the important pest species of flour beetle, and it is also an
      important quarantine insect. Here we sequenced and characterized the complete
      mitochondrial genome of T. audax, which was intercepted by Huangpu Custom in
      maize from America. The complete circular mitochondrial genome (mitogenome) of T.
      audax was 15,924 bp in length, containing 37 typical coding genes and one non
      coding AT-rich region. The mitogenome of T. audax exhibits a gene arrangement and
      content identical to the most common type in insects. All protein coding genes
      (PCGs) are start with a typical ATN initiation codon, except for the cox1, which
      use AAC as its start codon instead of ATN. Eleven genes use standard complete
      termination codon (nine TAA, two TAG), whereas the nad4 and nad5 genes end with
      single T. Except for trnS1 (AGN), all tRNA genes display typical secondary
      cloverleaf structures as those of other insects. The sizes of the large and small
      ribosomal RNA genes are 1288 and 780 bp, respectively. The AT content of the AT
      rich region is 81.36%. The 5 bp conserved motif TACTA was found in the intergenic
      region between trnS2 (UCN) and nad1. 

PMID- 24938097
TI  - The complete mitochondrial genome of Aythya ferina (Anatidae: Aythya).
AB  - The mitochondrial genome of Aythya ferina (Anatidae: Aythya) is a circular
      molecule of 16,616 bp in length, containing 13 protein-coding genes, 2 ribosomal
      RNA genes, 22 transfer RNA genes and one control region (D-loop). Overall base
      composition of the complete mitochondrial DNA was 29.42% A, 22.19% T, 32.83% C
      and 15.56% G. All the genes in A. ferina were distributed on the H-strand, except
      for the ND6 subunit gene and eight tRNA genes which were encoded on the L-strand.

PMID- 24938098
TI  - The complete mitochondrial genome of the Xupu goose.
AB  - Xupu goose is one of the famous native breed in China. In this work we reported
      the complete mitochondrial genome sequence of the Xupu goose in Hunan Province
      for the first time. The total length of the mitogenome is 16,742 bp, with the
      base composition of 30.21% for A, 22.70% for T, 32.02% for C, 15.08% for G, in
      the order C > A > T > G feature occurring in the Xupu goose. And it is made up of
      two ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and a non
      coding control region (D-loop region). The characteristics of the mitochondrial
      genome were analyzed and discussed in detail. The complete mitochondrial genome
      sequence of Xupu goose will be useful for the phylogenetics of poultry, and be
      available as basic data for the genetics and breeding. 

PMID- 24938099
TI  - The complete mitochondrial genome of Acanthastrea maxima (Cnidaria, Scleractinia,
      Lobophylliidae).
AB  - The complete nucleotide sequence of the mitochondrial genome of the scleractinian
      coral Acanthastrea maxima has been obtained, representing the first sequenced
      mitogenome of a member of the Lobophylliidae. The mitochondrial genome is 18,278 
      bp in length, the longest sequence among the robust corals sequenced mitogenome
      to date. The overall GC composition (33.7%) and the gene arrangement are similar
      to those of the other scleractinian corals, including 13 protein-coding genes, 2
      rRNA genes (rnl and rns) and 2 tRNA genes (tRNA-Met and tRNA-Trp). All genes
      except tRNA-Trp, atp8, cox1, tRNA-Met and rnl are engulfed by a large group I
      intron in the nad5 gene. A second group I intron of 1077 bp in length is inserted
      in the cox1 gene and it encodes a putative homing endonuclease. There are four
      regions of gene overlaps totalling 22 bp and nine intergenic spacer regions for a
      total of 2220 bp, of which the cox3-cox2 region may correspond to the putative
      control region. 

PMID- 24938101
TI  - The complete mitochondrial genome of the larvae Osbeck's grenadier anchovy Coilia
      mystus (Clupeiformes, Engraulidae) from Yangtze estuary.
AB  - The complete mitochondrial genome of the larvae Osbeck's grenadier anchovy Coilia
      mystus collected from Yangtze estuary was determined by next-generation
      sequencing. The mitogenome is a circular molecule 17,125 bp in length, including
      the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA genes, and a control region. The TAS, central CSB and CSB were
      detected in the control region. The gene contents of the mitogenome are identical
      to those observed in most bony fishes. 

PMID- 24938100
TI  - The complete mitochondrial genome of Paegniodes cupulatus (Ephemeroptera:
      Heptageniidae).
AB  - The complete mitochondrial genome of Paegniodes cupulatus (Ephemeroptera:
      Heptageniidae), which is sequenced for the first time here, is 15,715 bp in
      length, containing 13 protein-coding genes, 2 rRNAs, 22 tRNAs and a control
      region. The overall base composition of the genome is 33.1% for T, 20.7% for C,
      32.5% for A and 13.7% for G, with an AT bias of 65.6%. 

PMID- 24938102
TI  - Gene organization and complete sequence of the mitochondrial genome of Linwu
      mallard.
AB  - Linwu mallard is an excellent native breeds from Hunan province in China. This is
      the first study to determine the complete mitochondrial genome sequence of L.
      mallard using PCR-based amplification and Sanger sequencing. The characteristic
      of the entire mitochondrial genome was analyzed in detail, with the base
      composition of 29.19% A, 22.19% T, 32.83% C, 15.79% G in the L. mallard (16,605
      bp in length). It contained 2 ribosomal RNA genes, 13 protein-coding genes, 22
      transfer RNA genes and a major non-coding control region (D-loop region). The
      complete mitochondrial genome sequence of L. mallard will be useful for the
      phylogenetics of poultry, and be available as basic data for the genetics and
      breeding. 

PMID- 24938103
TI  - The complete mitochondrial genome of the wasp spider Argiope bruennichi (Araneae:
      Araneidae).
AB  - The complete mitochondrial genome of Argiope bruennichi is a circular molecule of
      14,063 bp in length, containing 13 protein-coding genes, 2 ribosomal RNAs, 21
      transfer RNAs, and a control region. The A + T content of the overall base
      composition of H-strand is 73.4% (T: 38.0%; C: 9.8%; A: 35.4%; G: 16.8%). ND6
      begins with ATG, ND4 and ATP6 begin with ATA, ND5 and COI begin with TTA, ND1,
      COII and COIII begin with TTG, and other five protein-coding genes begin with TTG
      as start codon. ND5, ND4L, ND6, COI, COII, COIII, ATP6 and ATP8 genes are
      terminated with TAA as stop codon, Cyt b, ND1 and ND2 end with TAG, and other two
      protein-coding genes end with T. 

PMID- 24938104
TI  - The complete mitochondrial genome of Nephila clavata (Araneae: Nephilidae)
      Chinese population.
AB  - The complete mitochondrial genome of Nephila clavata is a circular molecule of
      14,433 bp in length, containing 13 protein-coding genes, 2 ribosomal RNAs, 22
      transfer RNAs, and a control region. The A + T content of the overall base
      composition of H-strand is 76.1% (T: 40.0%; C: 9.2%; A: 36.1%; G: 14.7%). COI
      gene begins with TTA as start codon, COII gene begins with TTT as start codon,
      COIII gene begins with TTG as start codon, ND3, ND4L, ND6 and ATP8 genes begin
      with ATT as start codon, while other six protein-coding genes start with ATA as
      initiation codon. ND3, ND4, ND4L, ND5, COI, COII, ATP6 and ATP8 genes are
      terminated with TAA as stop codon, ND1, ND2, ND6 and Cyt b end with TAG, and
      COIII ends with TGA. 

PMID- 24938105
TI  - Complete mitochondrial genome of the holotype specimen of Wildemania schizophylla
      (Bangiales: Rhodophyta).
AB  - Ion Proton data was used to assemble the complete mitochondrial genome from the
      holotype specimen of Wildemania schizophylla (29,156 bp). The mitogenome contains
      50 genes, including 2 ribosomal RNA, 23 transfer RNA, 4 ribosomal proteins, 2
      ymfs, 3 open reading frames (ORFs), and 19 genes involved in cellular
      respiration. Although gene synteny is conserved, the mitogenome of W.
      schizophylla is significantly smaller due to the lack of large intronic ORFs
      present in the cytochrome oxidase locus of other Bangiales. The results support
      the recognition of Wildemania as distinct from Porphyra, and demonstrate that
      small amounts of type material are suitable for genomic studies. 

PMID- 24938106
TI  - The complete mitochondrial genome of the Linwu duck.
AB  - In this study, the complete mitochondrial genome sequence of the Linwu duck was
      first reported in Human Province, which was determined through PCR-based method.
      Linwu duck is one of the famous native breed in China. The total length of the
      mitogenome is 16,604 bp, with the base composition of 29.20% for A, 22.21% for T,
      32.82% for C, 15.78% for G, in the order C > A > T > G feature occurring in the
      Linwu duck. It is made up of 2 ribosomal RNA genes, 13 protein-coding genes, 22
      transfer RNA genes and one non-coding control region (D-loop region). The
      complete mitochondrial genome sequence of the Linwu duck in Human Province
      provides an important data for further study about genetic mechanism and
      breeding. 

PMID- 24938107
TI  - The complete mitochondrial genome sequence of Jinshaia abbreviata (Cypriniformes,
      Balitoridae).
AB  - Jinshaia abbreviata, belonging to the family Balitoridae in Cypriniformes, is
      endemic to the Upper Yangtze River with most population distributed in the Jinsha
      River. In this study, the complete mitochondrial genome of J. abbreviata was
      sequenced with its structure analyzed. The mitochondrial genome of J. abbreviata
      is similar to those of the typical vertebrates, 16,567 bp in length, including 13
      protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non
      coding control region (D-loop). The D-loop of J. abbreviata was characterized by
      one termination-associated sequence with two pair of motifs and six conserved
      sequence blocks (CSB-F, CSB-E, CSB-D, and CSB I-III). The mitogenome sequence of
      J. abbreviata could contribute to estimate the phylogenetic relationship of the
      Balitoridae. And further investigations with more Jinshaia species and
      individuals included need to be performed to better understand the speciation
      process and evolutionary history of the genus Jinshaia. 

PMID- 24938109
TI  - The complete mitochondrial genome of the Youxian duck.
AB  - Youxian duck is one of the famous native breed in China. In this work we reported
      the complete mitochondrial genome sequence of the Youxian duck in Human Province
      for the first time. The total length of the mitogenome is 16,606 bp, with the
      base composition of 29.21% for A, 22.18% for T, 32.83% for C, 15.78% for G, in
      the order C > A > T > G feature occurring in the Youxian duck. It is made up of
      two ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and one
      non-coding control region (D-loop region). The complete mitochondrial genome
      sequence of Youxian duck will be useful for the phylogenetics of poultry, and be
      available as basic data for the genetics and breeding. 

PMID- 24938108
TI  - Analysis of mtDNA, miR-155 and BACH1 expression in hearts from donors with and
      without Down syndrome.
AB  - Cancer patients with Down syndrome (DS) are at increased risk for anthracycline
      related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS
      may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the
      mtDNA(4977) deletion were quantitated in samples with- (n = 11) and without-DS (n
      = 31). Samples with-DS showed 30% lower mtDNA (DS(MT-ND1/18Sratio): 1.48 +/- 0.72
      versus non-DS(MT-ND1/18Sratio): 2.10 +/- 1.59; p = 0.647) and 30% higher
      frequency of the mtDNA(4977) deletion (DS(% frequency mtDNA(4977)) deletion:
      0.0086 +/- 0.0166 versus non-DS(% frequency mtDNA(4977)) deletion: 0.0066 +/-
      0.0124, p = 0.514) than samples without-DS. The BACH1 and microRNA-155 (miR-155)
      genes are located in chromosome 21, and their products have demonstrated roles
      during oxidative stress. BACH1 and miR-155 expression did not differ in hearts
      with- and without-DS. An association between BACH1 and miR-155 expression was
      detected in hearts without-DS, suggesting alterations between BACH1-miR-155
      interactions in the DS settings.

PMID- 24938110
TI  - Long-PCR based next generation sequencing of the whole mitochondrial genome of
      the peacock skate Pavoraja nitida (Elasmobranchii: Arhynchobatidae).
AB  - We determined the complete mitochondrial genome sequence (16,760 bp) of the
      peacock skate Pavoraja nitida using a long-PCR based next generation sequencing
      method. It has 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1
      control region in the typical vertebrate arrangement. Primers, protocols, and
      procedures used to obtain this mitogenome are provided. We anticipate that this
      approach will facilitate rapid collection of mitogenome sequences for studies on
      phylogenetic relationships, population genetics, and conservation of
      cartilaginous fishes. 

PMID- 24938111
TI  - Complete mitochondrial genome of Gallus domesticus (Galliformes: Phasianidae).
AB  - In this paper, the complete mitochondrial genome (mitogenome) sequence of Gallus
      domesticus was determined by long PCR and primer walking methods. The complete
      mitochondrial genome is 16,783 bp in length and contains 13 protein-coding genes,
      2 ribosomal RNA genes, 22 transfer RNA genes as well as a displacement loop (D
      loop). The overall base composition of the genome is A(30.25%), T(23.79%),
      C(32.44%), G(13.52%), respectively. The mitogenome of G. domesticus displayed
      novel gene order arrangement compared with published Gallus gallus var.
      domesticus to date. The mitogenome would contribute to resolving phylogenetic
      position and interrelationships of Gallus. 

PMID- 24938112
TI  - The complete chloroplast genome sequence of the Bambusa multiplex (Poaceae:
      Bambusoideae).
AB  - The complete nucleotide sequence of the Bambusa multiplex chloroplast genome
      (cpDNA) was determined in this study. The cpDNA was 139,394 bp in length,
      containing a pair of 21,798 bp inverted repeat regions (IR), which were separated
      by small and large single copy regions (SSC and LSC) of 12,875 and 82,923 bp,
      respectively. The B. multiplex cp genome encodes 129 predicted functional genes;
      110 are unique (77 protein-coding genes, 29 tRNA genes, 4 rRNA), 19 are
      duplicated in the IR regions and one gene extended into the IR region in the
      junctions between IR and SSC. 43.20% of the genome sequence encodes proteins. The
      B. multiplex cp genome is AT-rich (61.08%). In these genes, fourteen genes
      contained one intron, while one gene had two introns. 

PMID- 24938113
TI  - The complete chloroplast genome sequence of the Phyllostachys sulphurea (Poaceae:
      Bambusoideae).
AB  - The complete nucleotide sequence of the Phyllostachys sulphurea chloroplast
      genome (cpDNA) was determined in this study. The cpDNA was 139,731 bp in length,
      containing a pair of 21,798 bp inverted repeat regions (IR), which were separated
      by small and large single copy regions (SSC and LSC) of 12,879 and 83,256 bp,
      respectively. The P. sulphurea cp genome encodes 129 predicted functional genes;
      110 are unique (77 protein-coding genes, 29 tRNA genes, 4 rRNA), 19 are
      duplicated in the IR regions and one gene extended into the IR region in the
      junctions between IR and SSC. 43.06% of the genome sequence encodes proteins. The
      P. sulphurea cp genome is AT-rich (61.11%). In these genes, fourteen genes
      contained one intron, while one gene had two introns. 

PMID- 24938114
TI  - The complete mitochondrial genome of Russian sturgeon (Acipenser gueldenstaedti).
AB  - Russian sturgeon (Acipenser gueldenstaedti) belongs to the Acipenseriformes
      Acipenseridae. In this study, we sequenced and characterized the complete
      mitochondrial genome of A. gueldenstaedti from National Sturgeon Hatchery,
      Chinese Academy of Fishery Sciences. The circular mitochondrial genome was
      determined to be 16,595 bp in length including 13 protein-coding genes, 22
      transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs) and 1 control region. The
      complete mitochondrial genome of A. gueldenstaedti provides basic genome data for
      relative studies on Acipenseriformes. 

PMID- 24938115
TI  - The complete mitogenome of the Australian spiny crayfish Euastacus yarraensis
      (McCoy, 1888) (Crustacea: Decapoda: Parastacidae).
AB  - The mitochondrial genome sequence of the Australian crayfish, Euastacus
      yarraensis, is documented and compared with other Australian crayfish genera.
      Euastacus yarraensis has a mitogenome of 15,548 base pairs consisting of 13
      protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a non
      coding AT-rich region. The base composition of E. yarraensis mitogenome is 32.39%
      for T, 22.45% for C, 34.43% for A, and 10.73% for G, with an AT bias of 66.82%.
      The mitogenome gene order conforms to what is considered the primitive
      arrangement for parastacid crayfish. 

PMID- 24938116
TI  - Complete mitochondrial genome of Sinilabeo decorus tungting (Cypriniformes,
      Cyprinidae).
AB  - The complete mitochondrial genome of Sinilabeo decorus tungting was determined in
      this study. The gene composition, arrangement and transcriptional orientation in
      S. decorus tungting mitogenome were identical to most vertebrates. Two start
      codon patterns (ATG and GTG) and three stop codon patterns (TAG, TAA and T) were
      found in protein-coding genes. Only the tRNA-Ser2 could not fold into a typical
      clover-leaf secondary structure for lacking the dihydrouridine arm. Sequences
      alignment results suggest that the complete mitogenome of S. decorus tungting is
      an efficient tool to check species identification by comparing different gene
      sequences. 

PMID- 24938117
TI  - Complete mitochondrial genome of the pelagic stingray Pteroplatytrygon violacea
      (Myliobatiformes: Dasyatidae).
AB  - The pelagic stingray Pteroplatytrygon violacea is the only pelagic species of the
      Dasyatidae (Chondrichthyes: Elasmobranchii), which is widely distributed in all
      tropical, subtropical and temperate oceans. In this study, the complete
      mitochondrial genome of Pteroplatytrygon violacea was determined. It is 17,665 bp
      in length and contains 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA genes and 1 control region, with the typical gene order and
      direction of transcription of vertebrates. The overall nucleotide compositions of
      the whole mitogenome are 30.8% A, 26.9% C, 28.6% T and 13.7% G. The ND2 and CO1
      sequences are highly similar to the corresponding sequences of this species
      available in NCBI collected from the Atlantic sea. 

PMID- 24938118
TI  - MRI segmentation analysis in temporal lobe and idiopathic generalized epilepsy.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy
      (IGE) patients have each been associated with extensive brain atrophy findings,
      yet to date there are no reports of head to head comparison of both patient
      groups. Our aim was to assess and compare between tissue-specific and structural
      brain atrophy findings in TLE to IGE patients and to healthy controls (HC).
      METHODS: TLE patients were classified in TLE lesional (L-TLE) or non-lesional (NL
      TLE) based on presence or absence of MRI temporal structural abnormalities. High
      resolution 3 T MRI with automated segmentation by SIENAX and FIRST tools were
      performed in a group of patients with temporal lobe epilepsy (11 L-TLE and 15 NL
      TLE) and in15 IGE as well as in 26 HC. Normal brain volume (NBV), normal grey
      matter volume (NGMV), normal white matter volume (NWMV), and volumes of
      subcortical deep grey matter structures were quantified. Using regression
      analyses, differences between the groups in both volume and left/right asymmetry
      were evaluated. Additionally, laterality of results was also evaluated to
      separately quantify ipsilateral and contralateral effects in the TLE group.
      RESULTS: All epilepsy groups had significantly lower NBV and NWMV compared to HC
      (p < 0.001). L-TLE had lower hippocampal volume than HC and IGE (p = 0.001), and
      all epilepsy groups had significantly lower amygdala volume than HC (p < =
      0.004). In L-TLE, there was evidence of atrophy in both ipsilateral and
      contralateral structures. CONCLUSIONS: Our study revealed that TLE and IGE
      patients demonstrated similar overall tissue-specific brain atrophy, although
      specific structures differences were appreciated. L-TLE also appeared to behave
      differently than NL-TLE, with atrophy not limited to the ipsilateral side.

PMID- 24938119
TI  - What ICU nurses in different Austrian hospitals know and think about the Austrian
      organ donation law.
AB  - We previously reported a high level of information on the Austrian organ donation
      law in medical and non-medical students, patients and ICU nurses, whereby ICU
      nurses at University Hospital in Graz (n = 185) were very well informed and also
      had the most critical view of the Austrian organ donation law.This letter reports
      the extension of our previous study to ICU nurses from hospitals with a Christian
      background (n = 60). We found that ICU nurses in hospitals run by religious
      congregations considered the Austrian organ donation law to be good more often
      than did those at the University Hospital in Graz. A positive attitude was also
      influenced by gender and prior knowledge of the law.Reasons for this could be the
      Christian orientation of the hospitals or exposure to organ donation and
      transplantation procedures on the job.

PMID- 24938121
TI  - Prospecting for hyperaccumulators of trace elements: a review.
AB  - Specific plant species that can take up and accumulate abnormally high
      concentrations of elements in their aboveground tissues are referred to as
      "hyperaccumulators". The use of this term is justified in the case of enormous
      element-binding capacity of plants growing in their natural habitats and showing
      no toxicity symptoms. An increasing interest in the study of hyperaccumulators
      results from their potential applications in environmental biotechnology
      (phytoremediation, phytomining) and their emerging role in nanotechnology. The
      highest number of plant species with confirmed hyperaccumulative properties has
      been reported for hyperaccumulators of nickel, cadmium, zinc, manganese, arsenic
      and selenium. More limited data exist for plants accumulating other elements,
      including common pollutants (chromium, lead and boron) or elements of commercial
      value, such as copper, gold and rare earth elements. Different approaches have
      been used for the study of hyperaccumulators - geobotanical, chemical,
      biochemical and genetic. The chemical approach is the most important in screening
      for new hyperaccumulators. This article presents and critically reviews current
      trends in new hyperaccumulator research, emphasizing analytical methodology that
      is applied in identification of new hyperaccumulators of trace elements and its
      future perspectives. 

PMID- 24938120
TI  - Physicians' perceptions of shared decision-making behaviours: a qualitative study
      demonstrating the continued chasm between aspirations and clinical practice.
AB  - BACKGROUND: Shared Decision Making (SDM) is a process of engaging patients in
      health decisions that involve multiple medically appropriate treatment options.
      Despite growing public and policy support for patient engagement in health
      decisions, SDM is not widely practiced in clinical settings. OBJECTIVE: The
      purpose of our study was to explore clinicians' attitudes, beliefs and perceived
      social norms about engaging in SDM behaviours. DESIGN: Semi-structured
      qualitative interviews were conducted with physicians in five practice areas.
      SETTING AND PARTICIPANTS: This study was conducted at an academic medical centre
      in St. Louis, MO. The final sample included 20 physicians: five surgeons, five
      OB/GYNs, four medical oncologists, five internists and one emergency medicine
      physician. RESULTS: Clinicians described a number of beliefs and cultural- and
      system-level obstacles to the widespread implementation of SDM, such as how to
      engage in discussions of cost, uncertainty and clinical equipoise and how to
      engage patients across various socioeconomic backgrounds. CONCLUSION: Although a
      large number of participants expressed general support for incorporating SDM into
      practice, most held fundamentally inconsistent beliefs about practicing specific
      SDM behaviours. More extensive training of physicians at all levels (pre- and
      post-licensure) can help increase clinicians' confidence in SDM skills.
      Developing methods of integrating SDM into the institutional framework of
      hospitals and training programmes could also increase clinicians' motivation to
      practice SDM and work to change the culture of medicine such that SDM behaviours
      are supported.

PMID- 24938122
TI  - Minimal residual disease testing in hematologic malignancies and solid cancer.
AB  - Minimal residual disease (MRD) assays are of a great value to assess treatment
      efficacy and may provide prognostic information. This is particularly relevant in
      the era of targeted therapy where the introduction of MRD monitoring has
      fundamentally transformed the way in which cancer patients are managed. While MRD
      guidelines are well-established for chronic myeloid leukemia, acute promyelocytic
      leukemia and acute lymphoblastic leukemia, areas for continuing development are
      available. High level of standardization and regular external quality control
      rounds and recommendations for data interpretation remain essential to improve
      MRD monitoring. In this review, we describe the different applications of MRD
      assays in most frequent hematologic malignancies and solid cancer and provide an
      overview of the strengths and potential weaknesses of each method. 

PMID- 24938123
TI  - Structure- and context-based analysis of the GxGYxYP family reveals a new
      putative class of glycoside hydrolase.
AB  - BACKGROUND: Gut microbiome metagenomics has revealed many protein families and
      domains found largely or exclusively in that environment. Proteins containing the
      GxGYxYP domain are over-represented in the gut microbiota, and are found in
      Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron,
      suggesting their involvement in polysaccharide metabolism, but little else is
      known of the function of this domain. RESULTS: Genomic context and domain
      architecture analyses support a role for the GxGYxYP domain in carbohydrate
      metabolism. Sparse occurrences in eukaryotes are the result of lateral gene
      transfer. The structure of the GxGYxYP domain-containing protein encoded by the
      BT2193 locus reveals two structural domains, the first composed of three
      divergent repeats with no recognisable homology to previously solved structures,
      the second a more familiar seven-stranded beta/alpha barrel. Structure-based
      analyses including conservation mapping localise a presumed functional site to a
      cleft between the two domains of BT2193. Matching to a catalytic site template
      from a GH9 cellulase and other analyses point to a putative catalytic triad
      composed of Glu272, Asp331 and Asp333. CONCLUSIONS: We suggest that GxGYxYP
      containing proteins constitute a novel glycoside hydrolase family of as yet
      unknown specificity.

PMID- 24938124
TI  - Validation of the multi-dimensional scale of perceived social support (MSPSS) and
      the relationship between social support, intimate partner violence and antenatal
      depression in Malawi.
AB  - BACKGROUND: Lack of social support is an important risk factor for antenatal
      depression and anxiety in low- and middle-income countries. We translated,
      adapted and validated the Multi-dimensional Scale of Perceived Social Support
      (MSPSS) in order to study the relationship between perceived social support,
      intimate partner violence and antenatal depression in Malawi. METHODS: The MSPSS
      was translated and adapted into Chichewa and Chiyao. Five hundred and eighty
      three women attending an antenatal clinic were administered the MSPSS, depression
      screening measures, and a risk factor questionnaire including questions about
      intimate partner violence. A sub-sample of participants (n = 196) were
      interviewed using the Structured Clinical Interview for DSM-IV to diagnose major
      depressive episode. Validity of the MSPSS was evaluated by assessment of internal
      consistency, factor structure, and correlation with Self Reporting Questionnaire
      (SRQ) score and major depressive episode. We investigated associations between
      perception of support from different sources (significant other, family, and
      friends) and major depressive episode, and whether intimate partner violence was
      a moderator of these associations. RESULTS: In both Chichewa and Chiyao, the
      MSPSS had high internal consistency for the full scale and significant other,
      family, and friends subscales. MSPSS full scale and subscale scores were
      inversely associated with SRQ score and major depression diagnosis. Using
      principal components analysis, the MSPSS had the expected 3-factor structure in
      analysis of the whole sample. On confirmatory factor analysis, goodness-of-fit
      indices were better for a 3-factor model than for a 2-factor model, and met
      standard criteria when correlation between items was allowed. Lack of support
      from a significant other was the only MSPSS subscale that showed a significant
      association with depression on multivariate analysis, and this association was
      moderated by experience of intimate partner violence. CONCLUSIONS: The MSPSS is a
      valid measure of perceived social support in Malawi. Lack of support by a
      significant other is associated with depression in pregnant women who have
      experienced intimate partner violence in this setting.

PMID- 24938126
TI  - Is a flavonoid-rich diet with steamer cooking safe during calcineurin inhibitors
      therapy?
AB  - WHAT IS KNOWN AND OBJECTIVE: Dietary therapy is recommended for decreasing the
      symptoms of the metabolic syndrome and the risk of type 2 diabetes and
      cardiovascular diseases in subjects on calcineurin inhibitors. However, food-drug
      interactions may occur particularly with patients on such immunosuppressive
      therapy. This article comments on the benefit/risk assessment of a flavonoid-rich
      diet and steam-cooking of such food during calcineurin inhibitors therapy.
      COMMENT: Patients are commonly advised against consuming citrus fruits and
      juices, grape juice and green tea. High vegetable intake may however increase the
      risk of food-diet interactions by inhibiting drug metabolic enzymes and
      transporters. Vegetable glucosinolates are potential interactants and may lead to
      adverse effects of drugs with narrow therapeutic indices and in the presence of
      genetic polymorphism. Examples of food components with potential drug
      interactants include all members of the Brassicaceae family. WHAT IS NEW AND
      CONCLUSION: The potential additive and synergistic effects of flavonoids with
      other molecules in interfering with drug bioavailability need to be taken into
      account. The risk is highest with drugs with a narrow therapeutic index and in
      subjects with genetic polymorphisms of proteins involved in the disposition of
      those drugs.

PMID- 24938125
TI  - Repeatability and reproducibility of Galilei measurements in normal keratoconic
      and postrefractive corneas.
AB  - OBJECTIVE: To assess the repeatability and reproducibility of the anterior
      segment measurements performed with a dual Scheimpflug analyzer (Galilei) in
      normal, keratoconic and post-refractive surgery corneas. METHODS: To evaluate the
      repeatability, two additional measurements were performed by the first examiner.
      To assess reproducibility, this was later followed by a single reading by the
      second examiner. The following parameters were recorded and evaluated in this
      study; central corneal thickness (CCT), thinnest corneal thickness (TCT), mean
      total corneal power (TCP) in central (0-4mm), mean posterior corneal power (PCP)
      in central (0.5-2mm), anterior and posterior elevation (best fit sphere [BFS]) in
      central 8mm anterior and posterior eccentricity (E(2)) in central 8mm.
      Repeatability and reproducibility for each corneal parameter was assessed using
      the Bland-Altman analysis. RESULTS: Each of the three groups was consisted of 20
      subjects (totally 60 patients, 30 men and 30 women). The 95% LoA for
      repeatability was very small, indicating small discrepancies between measurements
      related to CCT. Acceptable repeatability was also achieved for the other
      parameters in each group. However, the 95% LoA for value TCP was larger in
      keratoconic eyes. The 95% LoA for reproducibility was also very small, and
      acceptable for all measured parameters in each group. In addition, the 95% LoA
      was larger for the measurement of CCT and TCT for postrefractive corneas.
      CONCLUSIONS: The anterior segment measurements provided by Galilei showed good
      repeatability and reproducibility for normal, keratoconic and postrefractive
      corneas.

PMID- 24938127
TI  - Membrane topology of transmembrane proteins: determinants and experimental tools.
AB  - Membrane topology refers to the two-dimensional structural information of a
      membrane protein that indicates the number of transmembrane (TM) segments and the
      orientation of soluble domains relative to the plane of the membrane. Since
      membrane proteins are co-translationally translocated across and inserted into
      the membrane, the TM segments orient themselves properly in an early stage of
      membrane protein biogenesis. Each membrane protein must contain some topogenic
      signals, but the translocation components and the membrane environment also
      influence the membrane topology of proteins. We discuss the factors that affect
      membrane protein orientation and have listed available experimental tools that
      can be used in determining membrane protein topology. 

PMID- 24938128
TI  - Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced
      impairment of insulin secretion.
AB  - ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a
      microsomal enzyme that regulates the elongation of C12-16 saturated and
      monounsaturated fatty acids and is related to the development of obesity-induced
      insulin resistance via the modification of the fatty acid composition. In this
      study, we investigated the role of systemic Elovl6 in the pancreatic islet and
      beta-cell function. Elovl6 is expressed in both islets and beta-cell lines. In
      mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture
      and beta-cell mass compared with those of the wild-type mice. However, when fed a
      high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin
      resistance observed in normal mice was attenuated and glucose-stimulated insulin
      secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those
      of the wild-type mice. Enhanced GSIS in the HFHS Elovl6(-/-) islets was
      associated with an increased ATP/ADP ratio and the suppression of ATF-3
      expression. Our findings suggest that Elovl6 could be involved in insulin
      secretory capacity per beta-cell and diabetes. 

PMID- 24938129
TI  - Overexpression of ERbeta is sufficient to inhibit hypoxia-inducible factor-1
      transactivation.
AB  - Estrogen receptor (ER) beta is predicted to play an important role in the
      prevention of breast cancer development and progression. We have previously shown
      that ERbeta suppresses hypoxia inducible factor (HIF)-1-mediated transcription
      through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via
      ubiquitination processes. In this study, we attempted to examine the effect of
      ERbeta specific ligand on HIF-1 inhibition in ERbeta positive PC3 cells and
      ERbeta transfected MCF-7 cells. ERbeta specific agonist diarylpropionitrile (DPN)
      stimulated estrogen response element (ERE)-luciferase activity in a similar
      fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT
      protein levels leading to an attenuation of hypoxia-induced hypoxia response
      element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment
      of DPN reduced vascular endothelial growth factor (VEGF) expression and co
      treatment with ERbeta specific antagonist PHTPP abrogated the effect in PC3
      cells. We then examined the effect of DPN in ERbeta transfected MCF-7 cells. HIF
      1 transcriptional activity repression by ERbeta was not further reduced by DPN,
      as examined by HRE-driven luciferase assays. Expression of ERbeta significantly
      decreased VEGF secretion and ARNT expression under hypoxic conditions. However,
      DPN did not additionally affect this suppression in MCF-7 cells transfected with
      ERbeta. This result shows that unliganded ERbeta is sufficient to inhibit HIF-1
      in systems of overexpression. 

PMID- 24938131
TI  - Robert M. Eiben MD (1922-2013).

PMID- 24938130
TI  - Aryl hydrocarbon receptor catabolic activity in bone metabolism is osteoclast
      dependent in vivo.
AB  - Bone mass is regulated by various molecules including endogenous factors as well
      as exogenous factors, such as nutrients and pollutants. Aryl hydrocarbon receptor
      (AhR) is known as a dioxin receptor and is responsible for various pathological
      and physiological processes. However, the role of AhR in bone homeostasis remains
      elusive because the cell type specific direct function of AhR has never been
      explored in vivo. Here, we show the cell type specific function of AhR in vivo in
      bone homeostasis. Systemic AhR knockout (AhRKO) mice exhibit increased bone mass
      with decreased resorption and decreased formation. Meanwhile, osteoclast specific
      AhRKO (AhR(DeltaOc/DeltaOc)) mice have increased bone mass with reduced bone
      resorption, although the mice lacking AhR in osteoblasts have a normal bone
      phenotype. Even under pathological conditions, AhR(DeltaOc/DeltaOc) mice are
      resistant to sex hormone deficiency-induced bone loss resulting from increased
      bone resorption. Furthermore, 3-methylcholanthrene, an AhR agonist, induces low
      bone mass with increased bone resorption in control mice, but not in
      AhR(DeltaOc/DeltaOc) mice. Taken together, cell type specific in vivo evidence
      for AhR functions indicates that osteoclastic AhR plays a significant role in
      maintenance of bone homeostasis, suggesting that inhibition of AhR in osteoclasts
      can be beneficial in the treatment of osteoporosis. 

PMID- 24938132
TI  - Cesare Lombroso MD, PhD (1917-2013).

PMID- 24938134
TI  - Oral corticosteroids versus adrenocorticotropic hormone for infantile spasms--an
      unfinished story.

PMID- 24938135
TI  - We cannot say whether attention deficit hyperactivity disorder exists, but we can
      find its molecular mechanisms.

PMID- 24938136
TI  - The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate
      dose intramuscular corticotropin for improvement of hypsarrhythmia in West
      syndrome: a randomized, single-blind, parallel clinical trial.
AB  - BACKGROUND: The role of therapy on improvement of hypsarrhythmia has not been
      systematically assessed. This study was performed to assess the efficacy of oral
      prednisolone and intramuscular adrenocorticotrophin hormone in improving
      hypsarrhythmia in West syndrome. METHOD: Children (2 months-2 years), with
      previously untreated West syndrome, were randomized to receive 40-60 IU every
      other day of intramuscular adrenocorticotrophin hormone or 40-60 mg/day of oral
      prednisolone for 14 days. Children with tuberous sclerosis were excluded.
      Improvement of hypsarrhythmia was assessed blindly using a hypsarrhythmia
      severity scale before and after completion of therapy. Adverse effects were
      assessed on day 14 using symptom diary. (Clinical trial registry identifier:
      SLCTR/2010/010.) RESULTS: From 92 newly diagnosed West syndrome infants, 48 were
      randomized to receive prednisolone and 44 to receive adrenocorticotrophin
      hormone. Eighty infants completed the posttreatment evaluation according to
      specifications. The hypsarrhythmia severity score, significantly improved with
      hormonal therapy for 2 weeks (10.45 +/- 2.65 vs 3.45 +/- 2.67); P < 0.01. When
      individual treatment arms were compared using mean differences in the improvement
      of scores, improvement in prednisolone arm (7.95 +/- 2.76) was significantly
      greater than that in the adrenocorticotrophin hormone arm (6.00 +/- 2.61); P <
      0.01. Both forms of therapy were tolerated well. Frequent crying, irritability,
      weight gain, increased appetite, and abdominal distension were more common (but
      not statistically significant) with prednisolone. CONCLUSIONS: Hypsarrhythmia
      severity score improved significantly with both hormonal therapies, but this
      improvement was significantly better with oral prednisolone than intramuscular
      adrenocorticotrophin hormone. This is the first ever documentation of a superior
      therapeutic role of oral steroids in West syndrome.

PMID- 24938137
TI  - Sleep disorders in children with Tourette syndrome.
AB  - BACKGROUND: The objective of this study was to determine the frequency, nature,
      and impact of sleep disorders in children and adolescents with Tourette syndrome
      and to raise awareness about their possible inclusion as a Tourette syndrome
      comorbidity. METHODS: Using a prospective questionnaire, we interviewed 123
      patients of age <=21 years with a confirmed diagnosis of Tourette syndrome. Each
      completed questionnaire was then reviewed in accordance with Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition, criteria for
      categorization to a form of sleep disorder. RESULTS: Of the 123 patients with
      Tourette syndrome, 75 (61%) had comorbid attention deficit hyperactivity disorder
      and 48 (39%) had Tourette without attention deficit hyperactivity disorder. The
      sleep problems observed included problems in the nature of sleep, abnormal
      behaviors during sleep, and impact of sleep disturbances on quality of life.
      Within these cohorts, 31 (65%) of the 48 Tourette-only patients and 48 (64%) of
      the 75 Tourette + attention deficit hyperactivity disorder patients could fit
      into some form of Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition, coded sleep disorders. Of the 48 Tourette + attention deficit
      hyperactivity disorder patients with sleep disorders, 36 (75%) had insomnia
      signs, which could be explained by the co-occurrence of attention deficit
      hyperactivity disorder and high stimulant use. However, 10 (32%) of the 31
      Tourette-only patients with sleep disorders had insomnia irrespective of
      attention deficit hyperactivity disorder or medication use. CONCLUSIONS: Sleep
      problems are common in children with Tourette syndrome irrespective of comorbid
      attention deficit hyperactivity disorder, justifying their inclusion as a
      comorbidity of Tourette syndrome.

PMID- 24938139
TI  - Development, reliability, and validity of the Alberta Perinatal Stroke Project
      Parental Outcome Measure.
AB  - BACKGROUND: Perinatal stroke is a leading cause of cerebral palsy and lifelong
      disability, although parent and family outcomes have not yet been studied in this
      specific population. The Alberta Perinatal Stroke Project Parental Outcome
      Measure was developed as a 26-item questionnaire on the impact of perinatal
      stroke on parents and families. METHODS: The items were derived from expert
      opinion and scientific literature on issues salient to parents of children with
      perinatal stroke, including guilt and blame, which are not well captured in
      existing measures of family impact. Data were collected from 82 mothers and 28
      fathers who completed the Parental Outcome Measure and related questionnaires
      (mean age, 39.5 years; mean child age, 7.4 years). Analyses examined the Parental
      Outcome Measure's internal consistency, test-retest reliability, validity, and
      factor structure. RESULTS: The Parental Outcome Measure demonstrated three unique
      theoretical constructs: Psychosocial Impact, Guilt, and Blame. The Parental
      Outcome Measure has excellent internal consistency (Cronbach alpha = 0.91) and
      very good test-retest reliability more than 2-5 weeks (r = 0.87). Regarding
      validity, the Parental Outcome Measure is sensitive to condition severity,
      accounts for additional variance in parent outcomes, and strongly correlates with
      measures of anxiety, depression, stress, quality of life, family functioning, and
      parent adjustment. CONCLUSIONS: The Parental Outcome Measure contributes to the
      literature as the first brief measure of family impact designed for parents of
      children with perinatal stroke.

PMID- 24938140
TI  - Magnetic resonance spectroscopy at term-equivalent age in extremely preterm
      infants: association with cognitive and language development.
AB  - BACKGROUND: Proton magnetic resonance spectroscopy can be used to assess brain
      integrity and maturation with age. OBJECTIVE: To compare regional cerebral
      magnetic resonance spectroscopy metabolite ratios in extremely low birth weight
      and healthy term control infants measured at term-equivalent age and to evaluate
      association between magnetic resonance spectroscopy metabolites and cognitive and
      language development at 18-22 months' corrected age. METHODS: Single-voxel point
      resolved spectroscopy sequence was performed in a prospective cohort of 43
      infants. Magnetic resonance spectroscopy metabolite ratios of N-acetylaspartate
      to choline-containing compounds and N-acetylaspartate to myo-inositiol in the
      hippocampus, cortex, and subventricular zone were associated with Bayley mental,
      cognitive, and language scores at 18-22 months' corrected age. RESULTS: The mean
      (+/-S.D.) gestation of the 31 extremely low birth weight population was 25 (+/
      1.1) weeks and mean (+/-S.D.) birth weight was 749 (+/-133.9) g. Compared with
      healthy term control infants, extremely low birth weight infants exhibited
      consistently lower N-acetylaspartate-to-choline-containing compounds ratios in
      our three regions of interest, with differences reaching statistical significance
      for the subventricular zone and cortex regions. In multiple linear regression
      analyses, N-acetylaspartate-to-choline-containing compounds ratio in the
      subventricular zone, N-acetylaspartate-to-choline-containing compounds ratio in
      the cortex, and N-acetylaspartate-to-myo-inositiol ratio in the subventricular
      zone were significantly associated with Bayley mental scores at 18-22 months'
      corrected age. CONCLUSIONS: Magnetic resonance spectroscopy metabolite
      abnormalities at term-equivalent age appear to be significantly associated with
      cognitive and language development in extremely low birth weight infants.

PMID- 24938141
TI  - Effect of low-level prenatal mercury exposure on neonate neurobehavioral
      development in China.
AB  - BACKGROUND: This study aimed to assess the effects of low-level prenatal mercury
      exposure on neonate neurobehavioral development in China. METHODS: In total, 418
      mother-neonate pairs were included in the study. Maternal urine, hair, and blood
      samples and cord blood samples were used to document prenatal exposure to
      mercury. The Neonatal Behavioral Neurological Assessment was used to estimate
      neurobehavioral development in the neonates at 3 days of age. RESULTS: Total
      mercury level was significantly higher in cord blood than that in maternal blood.
      A strong correlation was found between total mercury levels in maternal blood and
      those in cord blood (r = 0.7431; P < 0.0001). Trend analysis revealed that
      mothers who consumed more fish had higher blood and cord blood mercury levels
      (all P < 0.0001). Significant differences were also found between male and female
      cord blood mercury levels among groups with different fish consumption
      frequencies (all P < 0.0001). Cord blood mercury level was significantly
      associated with total Neonatal Behavioral Neurological Assessment scores (beta =
      0.03; standard error = 0.01; P = 0.0409), passive muscle tone (odds ratio = 1.07;
      95% confidence interval = 1.12-1.13; P = 0.0071), and active muscle tone (odds
      ratio = 1.06; 95% confidence interval = 1.01-1.11; P = 0.0170) scores after
      adjustment, respectively. CONCLUSIONS: Neonatal neurodevelopment was associated
      with prenatal exposure to mercury. Women with high mercury levels should avoid
      intake seafood excessively during pregnancy. Long-term effects of exposure to
      mercury on childhood development need to be further explored.

PMID- 24938142
TI  - Thiamine deficiency secondary to anorexia nervosa: an uncommon cause of
      peripheral neuropathy and Wernicke encephalopathy in adolescence.
AB  - INTRODUCTION: We present a developmentally appropriate adolescent boy who
      presented with upper and lower extremity glove-and-stocking paresthesias, distal
      weakness, vertigo, high-pitched voice, inattention, ataxia, and binocular
      diplopia after a voluntary 59-kg weight loss over 5 months. CLINICAL
      INVESTIGATIONS: Extensive investigations revealed serum thiamine levels <2
      nmol/L. Brain magnetic resonance imaging revealed symmetric abnormal T2
      prolongation of the mammillary bodies. Nerve conduction studies were consistent
      with axonal, length-dependent polyneuropathy. Together, these findings were
      diagnostic for peripheral polyneuropathy and Wernicke encephalopathy secondary to
      thiamine deficiency. CONCLUSION: This patient illustrates that eating disorders
      can be an uncommon cause of rapidly progressive paresthesias, weakness, and
      neurological decline due to thiamine deficiency.

PMID- 24938138
TI  - Impaired visual fixation at the age of 2 years in children born before the twenty
      eighth week of gestation. Antecedents and correlates in the multicenter ELGAN
      study.
AB  - BACKGROUND: Very little is known about the prevalence, antecedents, and
      correlates of impaired visual fixation in former very preterm newborns. METHODS:
      In the multicenter ELGAN study sample of 1057 infants born before the twenty
      eighth week of gestation who had a developmental assessment at 2 years corrected
      age, we identified 73 who were unable to follow an object across the midline. We
      compared them to the 984 infants who could follow an object across the midline.
      RESULTS: In this sample of very preterm newborns, those who had impaired visual
      fixation were much more likely than those without impaired visual fixation to
      have been born after the shortest of gestations (odds ratio, 3.2; 99% confidence
      interval, 1.4-7.5) and exposed to maternal aspirin (odds ratio, 5.2; 99%
      confidence interval, 2.2-12). They were also more likely than their peers to have
      had prethreshold retinopathy of prematurity (odds ratio, 4.1; 99% confidence
      interval, 1.8-9.0). At age 2 years, the children with impaired fixation were more
      likely than others to be unable to walk (even with assistance) (odds ratio, 7.5;
      99% confidence interval, 2.2-26) and have a Mental Development Index more than
      three standard deviations below the mean of a normative sample (odds ratio, 3.6;
      99% confidence interval, 1.4-8.2). CONCLUSION: Risk factors for brain and retinal
      damages, such as very low gestational age, appear to be risk factors for impaired
      visual fixation. This inference is further supported by the co-occurrence at age
      2 years of impaired visual fixation, inability to walk, and a very low Mental
      Development Index.

PMID- 24938143
TI  - "Light switch" mental status changes and irritable insomnia are two particularly
      salient features of anti-NMDA receptor antibody encephalitis.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate antibody encephalitis is becoming
      increasingly recognized as a cause of acute and subacute encephalopathy in both
      adults and children. The typical features of this disorder include some degree of
      encephalopathy, seizures, and often a movement disorder component. However, there
      is wide variability in its presentation, and diagnosis based on clinical features
      alone is often delayed. PATIENTS: We report a series of four of 12 patients
      observed at our children's hospital between 2011 and 2013 that we chose as
      particularly representative examples of two distinct clinical features. RESULTS:
      In these individuals with anti-N-methyl-D-aspartate receptor antibody
      encephalitis, we note a very rapid on-off state between responsiveness and
      nonresponsiveness and/or insomnia accompanied by extreme irritability. We
      describe the abrupt mental status shift as "light switch" because the patients
      can awaken in seconds from a completely nonresponsive state. The insomnia noted
      in our patients was also impressive and often present early in the patients'
      courses. CONCLUSIONS: Light switch mental status changes and irritable insomnia
      are important early features of anti-N-methyl-D-aspartate receptor antibody
      encephalitis that can signal the presence of this disorder. The exact
      pathophysiology of these two symptoms has not been fully elucidated, and we feel
      that presence of one or both of these symptoms early in the disease course should
      prompt immediate concern for this disorder.

PMID- 24938144
TI  - Use of ketamine in a newborn with refractory status epilepticus: a case report.
AB  - BACKGROUND: Brain malformations represent a major cause of refractory seizures.
      Standardized protocols to treat status epilepticus of newborn are not available
      in the literature. PATIENT: We present a case report of use of ketamine
      administered to a late preterm with Pierre Robin sequence, lissencephaly,
      polymicrogyria, and severe epilepsy. RESULTS: The infusion of ketamine permitted
      resolution of status epilepticus, cardiorespiratory stabilization, and improved
      parental care for 15 days. No significant side effects were noted. CONCLUSION: In
      the literature there are few studies regarding the use of ketamine for refractory
      status epilepticus, and only in nine of these described the use of, ketamine in
      children (2 months-18 years). This is the first report to document the effective
      use of ketamine in the newborn with status epilepticus.

PMID- 24938145
TI  - Vanishing white matter disease presenting as opsoclonus myoclonus syndrome in
      childhood--a case report and review of the literature.
AB  - BACKGROUND: Vanishing white matter disease is caused by mutations of the
      eukaryotic translation initiation factor 2B (EIF2B) and is a prevalent cause of
      inherited childhood leukoencephalopathy. Infantile and early childhood onset
      forms are associated with chronic progressive neurological signs, with episodes
      of rapid, neurological, and poor prognosis, with death in few months or years. In
      contrast, onset in late childhood and adult onset is rare and is associated with
      long-term survival because of milder signs and slow progression. PATIENT
      DESCRIPTION: We present a patient with a genetically proven vanishing white
      matter disease, typical brain MRI, presenting with opsoclonus myoclonus in early
      childhood and a delayed development of adult multifocal dystonia and
      schizoaffective disorder with continued survival. In addition we have also
      reviewed the relevant literature based on 42 previous articles summarizing
      clinical details of 318 individuals with vanishing white matter disease (single
      case reports to case series). In 283, genetic mutation of EIF2B was confirmed
      with the onset of vanishing white matter disease reported as antenatal (seven),
      infantile (eight), early childhood (107), between infantile and early childhood
      (20), late childhood (25), between early and late childhood (three), adult (68),
      and between late childhood and adult (21). CONCLUSIONS: Various movement
      disorders have been described with vanishing white matter disease either at
      presentation (mimicking an opsoclonus myoclonus syndrome) or in adulthood
      (dystonia and myoclonus) with continuing survival. Relatively preserved cognition
      is a novel presentation and is reported in this article along with a
      comprehensive literature review.

PMID- 24938146
TI  - Clinical and molecular analysis of a novel COLQ missense mutation causing
      congenital myasthenic syndrome in a Syrian family.
AB  - BACKGROUND: Congenital myasthenic syndromes with end-plate acetylcholinesterase
      deficiency are rare autosomal recessive disorders characterized by onset of the
      disease in early childhood, general weakness exacerbated by exertion,
      ophthalmoplegia, and refractoriness to anticholinesterase drugs. To date, all
      reported cases have been attributed to mutations in 18 genes including the COLQ
      gene that encodes a specific collagen that anchors acetylcholinesterase at the
      basal lamina of the neuromuscular junction. We identified a Syrian family with
      two children of consanguineous parents from two branches affected with congenital
      myasthenic syndrome with end-plate acetylcholinesterase deficiency. METHOD: The
      absence of acetylcholinesterase antibodies was demonstrated biochemically.
      Consequently, all the coding regions, exon-intron boundaries, and the 5' and 3'
      untranslated regions of the COLQ gene were amplified and sequenced using the
      Sanger sequencing method. RESULTS: We observed that the severity of the phenotype
      in the two affected children differed. One child had mild symptoms that included
      difficulties in gait and feeding with mild respiratory insufficiency. Her sibling
      died in the first months of life because of severe respiratory failure. The
      second patient had severe symptoms from birth and has been mechanically
      ventilated. DNA sequencing revealed a novel homozygous single nucleotide
      substitution mutation (c.1010T>C) in the COLQ gene in both patients. This
      substitution leads to a missense amino acid substitution at position 337 of the
      protein (p.Ile337Thr). This mutation is likely to impair ColQ's trimeric
      organization and therefore its anchoring within the synaptic basal lamina.
      CONCLUSION: We identified the molecular cause underlying congenital myasthenic
      syndrome in two patients. The marked phenotypic variation suggests that other
      factors including modifier genes may affect the severity of this disease.

PMID- 24938147
TI  - Chromosome 9q33q34 microdeletion with early infantile epileptic encephalopathy,
      severe dystonia, abnormal eye movements, and nephroureteral malformations.
AB  - BACKGROUND: Microdeletion of chromosome 9q33q34 is an emerging disease disorder
      associated with early infantile epileptic encephalopathy, intellectual
      disability, and a variety of movement disorders. PATIENT: We describe a male
      infant with early infantile epileptic encephalopathy with suppression-burst
      (Ohtahara syndrome) who carried a de novo 2.0-Mb microdeletion in chromosome
      9q33q34, including STXBP1. The previously reported examples of 9q33q34
      microdeletion including STXBP1 are reviewed. RESULTS: The patient developed
      infantile spasms at 4 months of age, and these were refractory to multiple
      antiepileptic drugs. He also developed severe dystonia during infancy, rotatory
      nystagmus, and nephroureteral malformations. Immunoglobulin and clobazam
      administered at 11 months were effective for the spasms, but profound psychomotor
      retardation remained. A comparative genomic hybridization array analysis and the
      fluorescence in situ hybridization analysis revealed a de novo 2.0-Mb
      microdeletion in chromosome 9q33q34, which encompasses STXBP1, ENG, SPTAN1, and
      52 other genes. A total of 14 patients (13 from the literature) with a 9q33q24
      microdeletion including STXBP1 were reviewed, five of them displayed early
      infantile epileptic encephalopathy with suppression-burst, and six of them had
      early-onset epilepsy but not early infantile epileptic encephalopathy. Dystonia
      has been previously described in 9q33q34 deletions involving TOR1A but not
      STXBP1. Neither abnormal eye movements nor nephroureteral malformations has been
      previously described. CONCLUSIONS: This patient adds unique clinical
      presentations of neurological and nephroureteral abnormalities to the features of
      9q33q34 microdeletion.

PMID- 24938148
TI  - Congenital lingual hemihyperplasia, Horner's syndrome, and agenesis of the
      internal carotid artery.

PMID- 24938149
TI  - Prenatal multicystic encephalopathy in isolated sulfite oxidase deficiency with a
      novel mutaion.

PMID- 24938150
TI  - Control of early seedling development by BES1/TPL/HDA19-mediated epigenetic
      regulation of ABI3.
AB  - Seed germination and young seedling establishment should be tightly regulated to
      maximize plant survival and thereby enable successful propagation. Plants have
      evolved developmental signalling networks to integrate environmental cues for
      proper control of these critical processes, in which brassinosteroids are known
      to attenuate ABA-mediated arrest of early seedling development; however, the
      underlying regulatory mechanism remains elusive. Here we reveal that a
      BES1/TPL/HDA19 repressor complex mediates the inhibitory action of
      brassinosteroids on ABA responses during early seedling development. BR-activated
      BES1 forms a transcriptional repressor complex with TPL-HDA19, which directly
      facilitates the histone deacetylation of ABI3 chromatin. This event leads to the
      transcriptional repression of ABI3 and consequently ABI5, major ABA signalling
      regulators in early seedling development. Our data reveal that the BR-activated
      BES1-TPL-HDA19 repressor complex controls epigenetic silencing of ABI3 and
      thereby suppresses the ABA signalling output during early seedling development. 

PMID- 24938151
TI  - Measuring professional satisfaction in Greek nurses: combination of qualitative
      and quantitative investigation to evaluate the validity and reliability of the
      Index of Work Satisfaction.
AB  - PURPOSE: The Index of Work Satisfaction (IWS) is a comprehensive scale assessing
      nurses' professional satisfaction. The aim of the present study was to explore:
      a) the applicability, reliability and validity of the Greek version of the IWS
      and b) contrasts among the factors addressed by IWS against the main themes
      emerging from a qualitative phenomenological investigation of nurses'
      professional experiences. METHODS: A descriptive correlational design was applied
      using a sample of 246 emergency and critical care nurses. Internal consistency
      and test-retest reliability were tested. Construct and content validity were
      assessed by factor analysis, and through qualitative phenomenological analysis
      with a purposive sample of 12 nurses. Scale factors were contrasted to
      qualitative themes to assure that IWS embraces all aspects of Greek nurses'
      professional satisfaction. RESULTS: The internal consistency (alpha = 0.81) and
      test-retest (tau = 1, p < 0.0001) reliability were adequate. Following
      appropriate modifications, factor analysis confirmed the construct validity of
      the scale and subscales. The qualitative data partially clarified the low
      reliability of one subscale. CONCLUSIONS: The Greek version of the IWS scale is
      supported for use in acute care. The mixed methods approach constitutes a
      powerful tool for transferring scales to different cultures and healthcare
      systems.

PMID- 24938152
TI  - An efficient asymmetric synthesis of (-)-lupinine.
AB  - The asymmetric synthesis of (-)-lupinine was achieved in 8 steps, 15% overall
      yield and >99 : 1 dr from commercially available starting materials. The strategy
      used for the construction of the quinolizidine scaffold involved reaction of an
      enantiopure tertiary dibenzylamine via two sequential ring-closures which both
      occurred with concomitant N-debenzylation. 

PMID- 24938154
TI  - [Not Available].

PMID- 24938153
TI  - [Family practice and psychiatry: 2 different areas, a large interface].

PMID- 24938155
TI  - [CME. Pleural effusion].

PMID- 24938157
TI  - [Comparison of management of ambulatory emergency patients in the family practice
      and the hospital emergency center].
AB  - The increase in health care cost is broadly discussed in the public, either in
      the hospital or ambulatory setting. With the present study we compared the
      invoice amount generated by a first doctor's advice in the general practitioner
      to the one in the emergency room. In addition, we compared the diagnostic
      procedures used in the general practice to the one in the hospital, and whether
      the choice of diagnostic procedures would substantially influence the invoice
      amount. The invoice amount in the hospital setting was on average CHF 197.-, i.
      e. 134%, higher compared to the general practice. The difference in the invoice
      amount was largely explained by more diagnostic procedures in the hospital.
      Moreover, part of the higher invoice amount was generated by the extensive
      physical examination by doctors in the hospital. 

PMID- 24938158
TI  - [Psychotropic drugs in general practice].
AB  - The article presents a user-friendly overview of psychotropic drugs which are
      helpful for the prescription in a primary care practice. The author recommends to
      get familiar with just a small selection of drugs first and second line. This
      means to know well about their effectiveness, short-and long-term side effects,
      interactions with other drugs and the necessary monitoring that should be done. 

PMID- 24938159
TI  - [Accidental falls in the elderly].
AB  - Falls in the elderly are common with consecutive high mortality and morbidity.
      Recent consecutive data focus on identification and therapy of intrinsic risk
      factors. Sarcopenia, imbalance and gait disorders represent the major risk
      factors. Sarcopenia is caused by a disequilibrium of protein synthesis and
      breakdown, probably in consequence of age-related changes in protein metabolism.
      Protein supplements in combination with strength training shows the best benefit.
      Disorders in balance and gait are caused by age-related or pathologic changes in
      a complex regulation system of gait. The individual fall risk correlates with the
      gait variability and even increases with bad dual task performance. Activities
      with high requirements of attention and body awareness are the most effective
      prevention for falls in the elderly (-50%). 

PMID- 24938160
TI  - [Risk of recurrence and postoperative intervertebral disc degeneration after
      lumbar intervertebral disc operation - is an anulus closure prosthesis the
      solution?].
AB  - A lumbar disc herniation is a frequent pathology. The incidence of a
      postoperative recurrence is between 1-18%. According to the current literature, a
      large anular defect and a limited perioperative microdiscectomy leads to an
      increased risk of recurrence. In contrast, a generous perioperative
      microdiscectomy comes along with an accelerated postoperative disc height loss
      and a progressive degenerative disc disease. The present work discusses the
      position of an anular-closure-device in respect of the problem risk of recurrence
      versus postoperative degenerative disc disease. 

PMID- 24938161
TI  - [Self injury behavior by cutting in young persons].

PMID- 24938162
TI  - [Atrial fibrillation: new anticoagulants are more effective and safer, but
      expensive].

PMID- 24938163
TI  - [Benign thyroid nodules have a very good prognosis - even when they become
      malignant].

PMID- 24938165
TI  - [CME ECG 45. Palpitations and broad complex tachycardia].

PMID- 24938167
TI  - [Figures in the history of medicine. Virginia Apgar].

PMID- 24938168
TI  - Actinopyrone D, a new downregulator of the molecular chaperone GRP78 from
      Streptomyces sp.
AB  - A new downregulator of the molecular chaperone GRP78, actinopyrone D, was
      isolated together with a known related compound, PM050463, from Streptomyces sp.
      RAG92. The molecular formula of actinopyrone D was established as C25H36O4 by
      high-resolution FAB-MS. NMR spectroscopic analysis revealed the structure of
      actinopyrone D, which consists of an alpha-methoxy-gamma-pyrone ring and a C17
      side chain containing a cis olefin moiety. Actinopyrone D and PM050463 dose
      dependently inhibited 2-deoxyglucose-induced luciferase expression in HT1080
      human fibrosarcoma cells transfected with a luciferase reporter plasmid
      containing the GRP78 promoter. Actinopyrone D inhibited GRP78 protein expression
      and induced cell death under endoplasmic reticulum stress. 

PMID- 24938171
TI  - Caffeine prevents human prion protein-mediated neurotoxicity through the
      induction of autophagy.
AB  - The human prion protein (PrP) fragment PrP(106-126) possesses the majority of the
      pathogenic properties associated with the infectious scrapie isoform of PrP,
      known as PrPSc. The accumulation of PrPSc in the brain of humans and animals
      affects the central nervous system. Recent epidemiological studies have suggested
      that caffeine, one of the major components of coffee, exerts protective effects
      against the development of neurodegeneration. However, the protective effects of
      caffeine against prion disease have not been reported to date. In this study, we
      therefore investigated the effects of caffeine on PrP-mediated neurotoxicity. The
      protein expression of the autophagosomal marker, LC3-II, was increased by
      caffeine in a dose-dependent manner, and the autophagy induced by caffeine
      protected the neuronal cells against PrP(106-126)-induced cell death. On the
      contrary, the downregulation of LC3-II using the autophagy inhibitors, 3
      methyladenine (3-MUAlpha) and wortmannin, prevented the caffeine-mediated
      neuroprotective effects. To the best of our knowledge, the present study provides
      the first evidence that treatment with caffeine protects human neuronal cells
      against prion-mediated neurotoxicity and these neuroprotective effects are
      mediated by caffeine-induced autophagy signals. Our data suggest that treatment
      with caffeine may be a novel therapeutic strategy for prion peptide-induced
      apoptosis.

PMID- 24938172
TI  - Helsingor statement on poly- and perfluorinated alkyl substances (PFASs).
AB  - In this discussion paper, the transition from long-chain poly- and perfluorinated
      alkyl substances (PFASs) to fluorinated alternatives is addressed. Long-chain
      PFASs include perfluoroalkyl carboxylic acids (PFCAs) with 7 or more
      perfluorinated carbons, perfluoroalkyl sulfonic acids (PFSAs) with 6 or more
      perfluorinated carbons, and their precursors. Because long-chain PFASs have been
      found to be persistent, bioaccumulative and toxic, they are being replaced by a
      wide range of fluorinated alternatives. We summarize key concerns about the
      potential impacts of fluorinated alternatives on human health and the environment
      in order to provide concise information for different stakeholders and the
      public. These concerns include, amongst others, the likelihood of fluorinated
      alternatives or their transformation products becoming ubiquitously present in
      the global environment; the need for more information on uses, properties and
      effects of fluorinated alternatives; the formation of persistent terminal
      transformation products including PFCAs and PFSAs; increasing environmental and
      human exposure and potential of adverse effects as a consequence of the high
      ultimate persistence and increasing usage of fluorinated alternatives; the high
      societal costs that would be caused if the uses, environmental fate, and adverse
      effects of fluorinated alternatives had to be investigated by publicly funded
      research; and the lack of consideration of non-persistent alternatives to long
      chain PFASs.

PMID- 24938174
TI  - Development of an active risk-based surveillance strategy for avian influenza in
      Cuba.
AB  - The authors designed a risk-based approach to the selection of poultry flocks to
      be sampled in order to further improve the sensitivity of avian influenza (AI)
      active surveillance programme in Cuba. The study focused on the western region of
      Cuba, which harbours nearly 70% of national poultry holdings and comprise several
      wetlands where migratory waterfowl settle (migratory waterfowl settlements -
      MWS). The model took into account the potential risk of commercial poultry farms
      in western Cuba contracting from migratory waterfowl of the orders Anseriformes
      and Charadriiformes through dispersion for pasturing of migratory birds around
      the MWS. We computed spatial risk index by geographical analysis with Python
      scripts in ESRI((r)) ArcGIS 10 on data projected in the reference system NAD 1927
      UTM17. Farms located closer to MWS had the highest values for the risk indicator
      pj and in total 31 farms were chosen for targeted surveillance during the risk
      period. The authors proposed to start active surveillance in the study area 3
      weeks after the onset of Anseriformes migration, with additional sampling
      repeated twice in the same selected poultry farms at 15 days interval (Comin et
      al., 2012; EFSA, 2008) to cover the whole migration season. In this way, the
      antibody detectability would be favoured in case of either a posterior AI
      introduction or enhancement of a previous seroprevalence under the sensitivity
      level. The model identified the areas with higher risk for AIV introduction from
      MW, aiming at selecting poultry premises for the application of risk-based
      surveillance. Given the infrequency of HPAI introduction into domestic poultry
      populations and the relative paucity of occurrences of LPAI epidemics, the
      evaluation of the effectiveness of this approach would require its application
      for several migration seasons to allow the collection of sufficient reliable
      data. 

PMID- 24938175
TI  - Diabetes education and care in a developing country: observations from Karachi,
      Pakistan.
AB  - OBJECTIVE: To explore the kind of care being received by a sample of middle
      income group subjects with diabetes in Karachi. DESIGN: Cross-sectional. PLACE
      AND DURATION OF STUDY: Raana Liaquat Ali Khan College of Home Economics, Karachi
      from January 2009 to September 2009. PATIENTS AND METHODS: Information was
      collected from 105 type 2 diabetics through a structured, pre-tested, self
      administered questionnaire distributed in two colleges only to those students who
      had any adult onset diabetic in their family. SPSS version 16 was used for data
      entry and analysis (e.g., chi-square tests). RESULTS: The mean duration of
      diabetes was 8.9 years. Random blood sugar, blood pressure check and urine test
      for sugar were the most frequently performed tests. Many important diabetes
      related tests had not been performed even on subjects with duration of diabetes
      of 10 years or more such as HbA1c had never been performed for 74% of subjects in
      this class. Test for circulation had never been performed for 93% of subjects
      with 1 year's diabetes duration and for 62% of subjects with duration of 10 years
      or more. More than 90% subjects received information about diet and causes of
      diabetes; >70% had been informed about diabetes complications, foot care, dental
      care, self monitoring of blood glucose and testing sugar in urine and only 48%
      had been educated about insulin injections. Physician was the source of this
      information for more than 70% of subjects. CONCLUSIONS: This study has explored
      insufficient clinical monitoring of diabetes complications and provision of
      casual diabetes education. These observations highlight the need for provision of
      appropriate diabetes education, both to health care team and professionals.

PMID- 24938173
TI  - Polybacterial human disease: the ills of social networking.
AB  - Polybacterial diseases involve multiple organisms that act collectively to
      facilitate disease progression. Although this phenomenon was highlighted early in
      the 20th century, recent technological advances in diagnostics have led to the
      appreciation that many infections are far more complex than originally believed.
      Furthermore, it is apparent that although most treatments focus on the dominant
      bacterial species in an infection, other microbes, including commensals, can have
      a profound impact on both the response to therapy and virulence. Very little is
      known about the molecular mechanisms that underpin interactions between bacteria
      during such infections. Here, we discuss recent studies identifying and
      characterizing mechanisms of bacterial interaction and the biological processes
      they govern during certain diseases. We also highlight how possible strategies
      for targeting these interbacterial interactions may afford a route towards
      development of new therapies, with consequences for disease control. 

PMID- 24938176
TI  - Fixed-dose combination PRO 160/120 of sabal and urtica extracts improves nocturia
      in men with LUTS suggestive of BPH: re-evaluation of four controlled clinical
      studies.
AB  - PURPOSE: To determine the effects of the herbal fixed-dose combination PRO
      160/120 (extracts from saw palmetto fruits and stinging nettle roots) on
      nocturnal voiding frequency, as measured by question 7 of the IPSS questionnaire,
      in patients with moderate-to-severe LUTS/BPH after 24 weeks of treatment compared
      to placebo, to the alpha-blocker tamsulosin, or to the 5alpha-reductase inhibitor
      finasteride. METHODS: The study is about post hoc evaluation of four published
      randomized, double-blind clinical trials on PRO 160/120, two compared with
      placebo, one with finasteride and one with tamsulosin. In addition, a pooled data
      analysis of the two placebo-controlled trials was conducted. RESULTS: We analyzed
      data from a total of 922 patients with a mean age of 66 years and a mean baseline
      nocturnal voiding frequency of 2.1. In the pooled analysis of placebo-controlled
      trials, nocturnal voids improved by 0.8 (29 %) with PRO 160/120 compared to 0.6
      (18 %) with placebo (p = 0.015, Wilcoxon test, one-tailed). The 69 % responder
      rate to PRO 160/120 was significantly superior to the placebo response (52 %; p =
      0.003, chi (2)-test, two-tailed). The majority of responders improved by 1
      void/night. Absolute improvements and response rates were consistently higher
      with PRO 160/120 than with placebo over a range of baseline nocturnal voiding
      frequencies. There were no differences between PRO 160/120 and finasteride or
      tamsulosin regarding absolute improvement of nocturnal voids or responds rates.
      CONCLUSION: PRO 160/120 significantly improved nocturnal voiding frequency
      compared to placebo and similar to tamsulosin or finasteride.

PMID- 24938177
TI  - Diet: from food to stone.
AB  - Dietary factors have been shown to influence urine composition and modulate the
      risk of kidney stone disease. With the rising prevalence of stone disease in many
      industrialized nations, dietary modification as therapy to improve lithogenic
      risk factors and prevent stone recurrence has gained appeal, as it is both
      relatively inexpensive and safe. While some dietary measures, such as a high
      fluid intake, have been shown in long-term randomized clinical trials to have
      durable effectiveness, other dietary factors have been subjected to only short
      term clinical or metabolic studies and their efficacy has been inferred. Herein,
      we review the current literature regarding the role of diet in stone formation,
      focusing on both the effect on urinary stone risk factors and the effect on stone
      recurrence. 

PMID- 24938179
TI  - Letter to the Editor concerning "Calculation of corrected body height in
      idiopathic scoliosis: comparison of four methods" by M. Tyrakowski et al. (Eur
      Spine J, doi:10.1007/s00586-014-3275-1).

PMID- 24938178
TI  - Criteria for successful correction of thoracolumbar/lumbar curves in AIS
      patients: results of risk model calculations using target outcomes and failure
      analysis.
AB  - INTRODUCTION: Failure to select the appropriate lowest instrumented vertebra
      (LIV) in selective lumbar fusion (SLF) for thoracolumbar/lumbar curves (LC) can
      result in adding-on in the lumbar curve (LC) or the need for fusion extension due
      to a decompensating thoracic curve (TC). The selection criteria that predict
      optimal outcomes still need to be refined. The objectives of the current study
      were to identify risk factors for failure of anterior scoliosis correction and
      fusion (ASF) as well as predictors of optimal outcomes and ASF efficacy for SLF.
      MATERIALS AND METHODS: A retrospective review of all patients (n = 245) with AIS
      who had anterior SLF at one institution was conducted. Optimal outcomes were
      defined as a target LC <= 20 degrees  and a target TC <= 30 degrees . The
      distance from the LIV to the SV was recorded. An increase in the LIV adjacent
      level disc angulation (LIVDA) >= 5 degrees  was defined as adding-on. An increase
      in the TC at follow-up was defined as TC-progression. Stepwise univariate and
      multivariate linear and logistic regression analyses were performed to identify
      criteria predicting the target LC and TC. A total of 68 % of the patients had the
      LIV at SV-2 (=2 levels above stable vertebra). RESULTS: The patients' average age
      was 17 years, the average fusion length was 4.6 levels, and the average follow-up
      time was 32 months. The preoperative LC was 49 +/- 14 degrees , the LC-bending
      was 22 +/- 13 degrees  (57 +/- 18 %), and the follow-up LC was 25 +/- 10 degrees
      . LC correction was 59 +/- 17% (p < 0.01). The preoperative TC was 39 +/- 13
      degrees , the TC-bending was 21 +/- 12 degrees , and the follow-up TC was 29 +/-
      13 degrees . The TC-correction was 32 +/- 19% (p < 0.01). At follow-up, 85
      patients (35%) had an LC <= 20 degrees , 110 patients (45 %) had a TC <= 30
      degrees . The follow-up LC and an LC <= 20 degrees  were predicted by LC-bending
      (p < 0.01, r = 0.6), preoperative LC (p < 0.01, r = 0.6). The logistic regression
      models could define patients at risk for failing the target LC <= 20 degrees  or
      TC <= 30 degrees . At follow-up, TC <= 30 degrees  was best predicted by the
      preoperative TC (p < 0.01, r = 0.8; OR 1.2) and TC-bending (p < 0.01, r = 0.8; OR
      1.06), with the logistic regression model revealing a correct prediction in 84 %
      of all cases. Among the patients, 8 % required late posterior surgery. Patients
      achieving the target LC <= 20 degrees  had a significantly reduced risk for
      failure (p = 0.01). Selecting an LIV at SV-1 vs. SV-2 significantly increased the
      chance of achieving a target LC <= 20 degrees  (p = 0.01) and reduced the risk of
      adding-on (p < 0.01). Predictors for failure also included a high preoperative LC
      (p = 0.02; OR 0.97), TC-bending (p < 0.01), and preoperative TC (p = 0.01). A cut
      off in the failure risk analysis was established at a TC of 38 degrees .
      Additionally, a significant cut-off for risk of adding-on was established at
      LIVDA <3.5 degrees . CONCLUSION: A high chance of achieving a target LC <= 20
      degrees  and a low risk of revision was dependent on LC-bending, preoperative LC
      and TC, and a LIV at SV-1 with non-parallel LIVDA. Our risk model analysis may
      support the selection of a safe LIV to achieve the target LC.

PMID- 24938180
TI  - Posterior C1-C2 screw and rod instrument for reduction and fixation of basilar
      invagination with atlantoaxial dislocation.
AB  - PURPOSE: To report the surgical technique and preliminary clinical results for
      the treatment of basilar invagination (BI) with atlantoaxial dislocation (AAD) by
      posterior C1-C2 pedicle screw and rod instrument. METHODS: Between July 2012 and
      August 2013, 33 patients who had BI with AAD underwent surgery at our
      institution. Pre and postoperative three-dimensional computed tomographic (CT)
      scans were performed to assess the degree of dislocation. Magnetic resonance (MR)
      imaging was used to evaluate the compression of the medulla oblongata. For all
      patients, reduction of the AAD was conducted by two steps: fastening nuts and
      rods was performed to achieve the horizontal reduction. Distraction between C1
      and C2 screws was performed to obtain the vertical reduction. RESULTS: No
      neurovascular injury occurred during surgery. Follow-up ranged from 6 to 15
      months (mean 10.38 months) in 32 patients. Post-operative three-dimensional CT
      showed that complete horizontal reduction was obtained in 30/33 (90.9%), and
      complete vertical reduction was obtained in 31/33 (93.9%). The repeated three
      dimensional CT and MR image demonstrated that bony fusion and the decompression
      of the medulla oblongata were obtained in all patients. Clinical symptoms
      improved significantly 3 months after surgery. CONCLUSIONS: This C1-C2 pedicle
      screw and rod instrument is a promising technique for the treatment of BI with
      AAD.

PMID- 24938181
TI  - Treatment of basilar invagination.
AB  - PURPOSE: Basilar invagination is a rare craniocervical malformation which may
      lead to neurological deficits related to compression of brainstem and upper
      cervical cord as well as instability of the craniocervical junction. This study
      presents results of a treatment algorithm developed over a 20-year period
      focussing on anatomical findings, short-term and long-term outcomes. METHODS: 69
      patients with basilar invagination (mean age 41 +/- 18 years, history 64 +/- 85
      months) were encountered. The clinical courses were documented with a score
      system for individual neurological symptoms for short-term results after 3 and 12
      months. Long-term outcomes were analyzed with Kaplan-Meier statistics. RESULTS:
      Patients with (n = 31) or without (n = 38) ventral compression were
      distinguished. 25 patients declined an operation, while 44 patients underwent 48
      operations. Surgical management depended on the presence of ventral compression
      and segmentation anomalies between occiput and C3, signs of instability and
      presence of caudal cranial nerve dysfunctions. 16 patients without ventral
      compression underwent foramen magnum decompressions without fusion. 19 patients
      with ventral compression and abnormalities of segmentation or evidence of
      instability underwent a foramen magnum decompression with craniocervical (n = 18)
      or C1/2 (n = 1) stabilization. In nine patients with severe ventral compression
      and caudal cranial nerve deficits, a transoral resection of the odontoid was
      combined with a posterior decompression and fusion. Within the first
      postoperative year neurological scores improved for all symptoms in each patient
      group. In the long-term, postoperative deteriorations were related exclusively to
      instabilities either becoming manifest after a foramen magnum decompression in
      three or as a result of hardware failures in two patients. CONCLUSIONS: The great
      majority of patients with basilar invagination report postoperative improvements
      with this management algorithm. Most patients without ventral compression can be
      managed by foramen magnum decompression alone. The majority of patients with
      ventral compression can be treated by posterior decompression, realignment and
      stabilization alone, reserving anterior decompressions for patients with
      profound, symptomatic brainstem compression.

PMID- 24938182
TI  - Genetic structure and hybridization in the species group of Ficus auriculata: can
      closely related sympatric Ficus species retain their genetic identity while
      sharing pollinators?
AB  - Obligate mutualistic nursery pollination systems between insects and plants have
      led to substantial codiversification involving at least some parallel
      cladogenesis, as documented in Yucca, Ficus and Phyllanthaceae. In such systems,
      pollinators are generally species specific thus limiting hybridization and
      introgression among interfertile host species. Nevertheless, in the three
      systems, cases of one insect pollinating several plant species are reported. In
      most cases, host plants sharing pollinators are allopatric. However, in the case
      of the species group of Ficus auriculata, forms may co-occur over large parts of
      their range. We show here that the species group of F. auriculata is constituted
      by four well-defined genetic entities that share pollinators. We detected hybrids
      in nature mainly when both parental forms were growing nearby. Controlled crosses
      showed that F1 offspring could be successfully backcrossed. Hence, despite
      sharing pollinators and despite hybrid viability, the different forms have
      preserved their genetic and morphological identity. We propose that ecological
      differentiation among forms coupled with limited overlap of reproductive season
      has facilitated the maintenance of these interfertile forms. As such,
      establishment of pollinator host specificity may not be a prerequisite for
      sympatric diversification in Ficus. 

PMID- 24938183
TI  - Potential clinical implications of BRAF mutations in histiocytic proliferations.
AB  - For a growing number of tumors the BRAF V600E mutation carries therapeutic
      relevance. In histiocytic proliferations the distribution of BRAF mutations and
      their relevance has not been clarified. Here we present a retrospective
      genotyping study and a prospective observational study of a patient treated with
      a BRAF inhibitor. Genotyping of 69 histiocytic lesions revealed that 23/48
      Langerhans cell lesions were BRAF-V600E-mutant whereas all non-Langerhans cell
      lesions (including dendritic cell sarcoma, juvenile xanthogranuloma, Rosai
      Dorfman disease, and granular cell tumor) were wild-type. A metareview of 29
      publications showed an overall mutation frequency of 48.5% and with N=653 samples
      this frequency is well defined. The BRAF mutation status cannot be predicted
      based on clinical parameters and outcome analysis showed no difference.
      Genotyping identified a 45 year-old woman with an aggressive and treatment
      refractory, ultrastructurally confirmed systemic BRAF-mutant LCH. Prior
      treatments included glucocorticoid/vinblastine and cladribine-monotherapy.
      Treatment with vemurafenib over 3 months resulted in a dramatic metabolic
      response by FDG-PET and stable radiographic disease; the patient experienced
      progression after 6 months. In conclusion, BRAF mutations in histiocytic
      proliferations are restricted to lesions of the Langerhans-cell type. While for
      most LCH-patients efficient therapies are available, patients with BRAF mutations
      may benefit from the BRAF inhibitor vemurafenib. 

PMID- 24938184
TI  - Prostate specific antigen testing is associated with men's psychological and
      physical health and their healthcare utilisation in a nationally representative
      sample: a cross-sectional study.
AB  - BACKGROUND: Prostate cancer incidence has risen considerably in recent years,
      primarily due to Prostate Specific Antigen (PSA) testing in primary care. The
      objective of this study was to investigate associations between PSA testing and
      the psychological and physical health, and healthcare utilisation of men in a
      population where PSA testing is widespread. METHODS: A cross-sectional study was
      carried out in a population-representative sample of men >= 50 years enrolled in
      The Irish Longitudinal Study on Ageing (TILDA). TILDA participants underwent
      structured interviews, health assessments and completed standardised
      questionnaires. Men were classified as ever/never having received a PSA test.
      Multivariate logistic regression (Odds Ratios (OR) and 95% Confidence Intervals
      (CI) was used to determine associations between PSA testing, and men's
      psychological and physical health and healthcare utilisation. RESULTS: This
      analysis included 3,628 men, 68.2% of whom ever had a PSA test. In adjusted
      analysis, men with sub-threshold depression were significantly less likely to
      have had a PSA test, (OR=0.79, 95% CI 0.64-0.97). Likelihood of having a PSA test
      was inversely associated with anxiety, but this was not significant (OR=0.79, 95%
      CI 0.57-1.09). Frailty (OR=0.61, 95% CI 0.31-1.05) and eligibility for free
      primary care (OR=0.63, 95% CI 0.52-0.77) were also inversely associated with PSA
      testing. Positive associations were observed between PSA testing and more chronic
      illnesses (OR=1.11, 95% CI 1.05-1.19), more primary care visits (OR=1.03, 95% CI
      1.01-1.05) and preventative health practices, including cholesterol testing and
      influenza vaccination (OR=1.35, 95% CI 1.13-1.60). CONCLUSIONS: Men's
      psychological and physical health and their healthcare utilisation are associated
      with PSA testing in primary care. The association between poorer psychological
      health, in particular sub-threshold depression, and reduced likelihood of PSA
      testing in primary care requires further investigation. These findings may have
      wider implications for other cancer screening.

PMID- 24938185
TI  - Influences of attribution and stigma on working relationships with providers
      practicing Western psychiatry in the Taiwanese context.
AB  - This study examined influences of causal attributions of schizophrenia and
      perceived and internalized mental illness stigma on perceived working alliance
      with, and informational support received from doctors practicing Western
      psychiatry in the Taiwanese social-cultural context. This cross-sectional
      quantitative study used a non-probability, purposive sampling technique to
      recruit 212 Taiwanese diagnosed with schizophrenia from Taiwanese Alliance of the
      Mentally Ill, 4 community mental health rehabilitation centres and 2 psychiatric
      hospitals between July 2012 and March 2013. Linear regression models were used
      for analysis. The results showed that environmental attributions were positively
      associated with both perceived working alliance and perceived informational
      support, while supernatural attributions were negatively associated with
      perceived working alliance and perceived informational support. Perceived stigma
      had a negative association with perceived working alliance. The discrimination
      domain of internalized stigma specifically had a positive association with
      perceived working alliance, while the withdraw domain had a negative association
      with perceived informational support. Findings inform the importance of
      culturally sensitive practices in developing an effective working relationship.
      Western psychiatric care providers need to explore consumers' casual attributions
      of mental illness and understand the impact of stigma so that providers may
      successfully engage consumers in care and provide tailored illness education and
      information. 

PMID- 24938186
TI  - Frequency and clinicopathological features of fibroelastotic changes in the
      gastrointestinal tract.
AB  - Fibroelastotic changes (FEC) and especially elastotic polyps of the
      gastrointestinal (GI) tract are considered rare benign lesions. They consist of
      accumulations of elastic fibers within the mucosal, submucosal, or muscular
      layer, occurring in all parts of the GI tract and often appearing as polyps, but
      also as diffuse non-polyp-forming deposits. They have been the subject of only a
      few studies. To explore the clinical and histopathological features of FEC in the
      GI tract, a series of 162 elastotic lesions was collected within a 2-year period.
      The clinical data and endoscopic findings were correlated. FEC appeared as polyp
      forming lesions of the large intestine in 23 samples (14 %), all other samples
      concerning histological findings without an identifiable gross mass. Frequently
      related findings were postinterventional status (9 %), previous irradiation (7
      %), and history of GI lymphoma (4 %). Eight samples (5 %) presented
      endoscopically with lesions justifying surgical intervention. We identified three
      different histological patterns of FEC, which we have called fibroelastosis,
      angioelastosis, and elastofibroma. Consistent with previous studies, CD34
      immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an
      increase of CD34-positive mesenchymal cells in 95 % of immunostained samples,
      suggesting a potential role for CD34-positive mesenchymal cells in the
      accumulation of elastic fibers. In conclusion, FEC are more common in the GI
      tract than previously recognized. They often present as a benign polyp. Many
      accompany other diseases like ulcers and atrophic gastritis or represent a
      residual finding after an intervention.

PMID- 24938187
TI  - Effect of mechanical loads on stability of nanodomains in ferroelectric ultrathin
      films: towards flexible erasing of the non-volatile memories.
AB  - Intensive investigations have been drawn on nanoscale ferroelectrics for their
      prospective applications such as developing memory devices. In contrast with the
      commonly used electrical means to process (i.e., read, write or erase) the
      information carried by ferroelectric domains, at present, mechanisms of non
      electrical processing ferroelectric domains are relatively lacking. Here we make
      a systematical investigation on the stability of 180 degrees  cylindrical domains
      in ferroelectric nanofilms subjected to macroscopic mechanical loads, and explore
      the possibility of mechanical erasing. Effects of domain size, film thickness,
      temperature and different mechanical loads, including uniform strain, cylindrical
      bending and wavy bending, have been revealed. It is found that the stability of a
      cylindrical domain depends on its radius, temperature and film thickness. More
      importantly, mechanical loads have great controllability on the stability of
      cylindrical domains, with the critical radius nonlinearly sensitive to both
      strain and strain gradient. This indicates that erasing cylindrical domain can be
      achieved by changing the strain state of nanofilm. Based on the calculated phase
      diagrams, we successfully simulate several mechanical erasing processes on 4 * 4
      bits memory devices. Our study sheds light on prospective device applications of
      ferroelectrics involving mechanical loads, such as flexible memory devices and
      other micro-electromechanical systems. 

PMID- 24938188
TI  - The neurotoxicity of 5-S-cysteinyldopamine is mediated by the early activation of
      ERK1/2 followed by the subsequent activation of ASK1/JNK1/2 pro-apoptotic
      signalling.
AB  - Parkinson's disease is characterized by the progressive and selective loss of
      dopaminergic neurons in the substantia nigra. It has been postulated that
      endogenously formed CysDA (5-S-cysteinyldopamine) and its metabolites may be, in
      part, responsible for this selective neuronal loss, although the mechanisms by
      which they contribute to such neurotoxicity are not understood. Exposure of
      neurons in culture to CysDA caused cell injury, apparent 12-48 h post-exposure. A
      portion of the neuronal death induced by CysDA was preceded by a rapid uptake and
      intracellular oxidation of CysDA, leading to an acute and transient activation of
      ERK2 (extracellular-signal-regulated kinase 2) and caspase 8. The oxidation of
      CysDA also induced the activation of apoptosis signal-regulating kinase 1 via its
      de-phosphorylation at Ser967, the phosphorylation of JNK (c-Jun N-terminal
      kinase) and c-Jun (Ser73) as well as the activation of p38, caspase 3, caspase 8,
      caspase 7 and caspase 9. Concurrently, the inhibition of complex I by the
      dihydrobenzothiazine DHBT-1 [7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4
      benzothiazine-3-carboxylic acid], formed from the intracellular oxidation of
      CysDA, induces complex I inhibition and the subsequent release of cytochrome c
      which further potentiates pro-apoptotic mechanisms. Our data suggest a novel
      comprehensive mechanism for CysDA that may hold relevance for the selective
      neuronal loss observed in Parkinson's disease.

PMID- 24938189
TI  - Pain in rheumatic diseases: how relevant is it?
AB  - Pain, a complex phenomenon influenced by a series of genetic, biological,
      psychological and social factors, is a major component of many rheumatological
      conditions and the result of physiological interactions between central and
      peripheral nervous system signalling. It may be acute or chronic (generally
      defined as lasting >= three months): acute pain is often primarily attributable
      to inflammation and/or damage to peripheral structures (i.e. nociceptive input),
      whereas chronic pain is more likely to be due to input from the central nervous
      system (CNS). The many different aspects of pain mean that rheumatologists and
      other clinicians need to have enough expertise to diagnose the type of pain
      correctly and treat it appropriately. However, most rheumatologists receive
      little formal training concerning contemporary theories of pain processing or
      management, and this may affect the clinical results of any specific target
      therapy. 

PMID- 24938190
TI  - Physiopathology of pain in rheumatology.
AB  - Pain is the main manifestation of many rheumatic diseases (be they overtly
      inflammatory such as rheumatoid arthritis or dysfunctional such as fibromyalgia)
      but, at least initially, the mechanisms involved in the genesis, amplification
      and chronicisation of the persistent pain characterising the various conditions
      can be very different. The main peripheral mechanism underlying acute nociceptive
      pain is a change in the activity of the nociceptors located in the affected
      anatomical structures (joints, tendons and ligaments), which makes them more
      sensitive to normally painful stimuli (hyperalgesia) or normally non-painful
      stimuli (allodynia). This physiopathological mechanism of peripheral
      sensitisation plays a primary role in rheumatic diseases characterised by acute
      inflammation, such as the arthritides due to microcrystals. In the case of
      chronic rheumatic diseases that do not regress spontaneously, functional and
      structural central nervous system changes cause a generalised reduction in the
      pain threshold that is not limited to the anatomical structures involved, thus
      leading to the appearance of hyperalgesia and allodynia in many, if not all body
      districts. This is the physiopathological basis of chronic, widespread
      musculoskeletal pain. 

PMID- 24938191
TI  - Pharmacology of pain.
AB  - This article discusses the mechanisms of action of the main drugs used to treat
      pain, in particular inflammatory pain. The drugs are described following a
      classification based on the steps of pain processing that they primarily affect. 

PMID- 24938192
TI  - Pain in rheumatoid arthritis: a critical review.
AB  - Patients with rheumatoid arthritis (RA) are frequently afflicted by pain, which
      may be caused by joint inflammation (leading to structural joint damage) or
      secondary osteoarthritis, and may be increased by central sensitisation. Non
      inflammatory pain may also confuse the assessment of disease activity, and so the
      aim of treatment is not only to combat inflammatory disease, but also relieve
      painful symptoms. In order to ensure effective treatment stratification, it is
      necessary to record a patients medical history in detail, perform a physical
      examination, and objectively assess synovitis and joint damage. The management of
      pain requires various approaches that include pharmacological analgesia and
      biological and non-biological treatments. Although joint replacement surgery can
      significantly improve RA-related pain, it may only be available to patients with
      the most severe advanced disease. 

PMID- 24938193
TI  - Chronic widespread pain in spondyloarthritis.
AB  - The pain associated with spondyloarthritis (SpA) can be intense, persistent and
      disabling. It frequently has a multifactorial, simultaneously central and
      peripheral origin, and may be due to currently active inflammation, or joint
      damage and tissue destruction arising from a previous inflammatory condition.
      Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory
      drugs, but many patients continue to experience moderate pain due to alterations
      in the mechanisms that regulate central pain, as in the case of the chronic
      widespread pain (CWP) that characterises fibromyalgia (FM). The importance of
      distinguishing SpA and FM is underlined by the fact that SpA is currently treated
      with costly drugs such as tumour necrosis factor (TNF) inhibitors, and direct
      costs are higher in patients with concomitant CWP or FM than in those with FM or
      SpA alone. Optimal treatment needs to take into account symptoms such as fatigue,
      mood, sleep, and the overall quality of life, and is based on the use of
      tricyclic antidepressants or selective serotonin reuptake inhibitors such as
      fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease
      modifying drugs. 

PMID- 24938194
TI  - Pain and systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      heterogeneous clinical manifestations involving virtually the entire body. The
      pain in SLE can have different causes. The SLE classification criteria include
      mainly the musculoskeletal manifestations of pain, which are commonly reported as
      initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic
      widespread pain, which is typical of fibromyalgia (FM), is frequently associated
      with SLE. The aim of this review is to describe widespread pain and fatigue in
      SLE, and the association of SLE and FM. Although secondary FM is not correlated
      with the disease activity, it may interfere with the daily activities of SLE
      patients. Therefore it is necessary to identify its symptoms and treat them
      promptly to improve the quality of life of patients. In conclusion, it is
      essential to identify the origin of pain in SLE in order to avoid dangerous over
      treatment in patients with co-existing widespread pain and FM. 

PMID- 24938195
TI  - Pain in Sjogren's syndrome.
AB  - Sjogren's syndrome (SjS) is an autoimmune disease that affects the salivary and
      lacrimal glands, but it can also have extra-glandular manifestations. Although
      pain has not yet been fully studied and characterized, it is a symptom that can
      be often found in patients with SjS, who mainly complain of neuropathic pain,
      followed by nociceptive pain. The latter when combined with widespread
      dysfunctional symptoms is defined fibromyalgia. The aim of this work is to
      analyze the scientific literature on the presence of pain in patients with
      primary Sjogren's syndrome. 

PMID- 24938196
TI  - Pain in systemic sclerosis.
AB  - Chronic pain is a healthcare problem that significantly affects the mental
      health, and the professional and private life of patients. It can complicate many
      disorders and represents a common symptom of rheumatologic diseases, but the data
      on its prevalence is still limited. Pain is a ubiquitous problem in systemic
      sclerosis (SSc). SSc-related pain has been studied on the basis of biomedical
      models and is considered a symptom caused by the disease activity or previous
      tissue damage. Effective pain management is a primary goal of the treatment
      strategy, although this symptom in SSc has not yet been investigated in detail.
      However, these patients do not all respond adequately to pharmacological pain
      therapies, therefore in these cases a multimodal approach needs to be
      adopted.This paper must be considered as retracted due to a plagiarism
      misconduct.See the Retraction note at:
      https://doi.org/10.4081/reumatismo.2018.1171

PMID- 24938197
TI  - Pain and microcrystalline arthritis.
AB  - Microcrystals are responsible for some of the most common and complex
      arthropathies which are often accompanied by intense, severe pain and
      inflammatory reactions. The main pathogens are crystals of monosodium urate
      (MSU), responsible for the gout, calcium pyrophosphate (CPP), which deposits also
      in various clinical forms of arthopathies, and basic calcium phosphate associated
      with osteoarthritis. In this context, the microcrystal arthritis is characterized
      by multiple, acute attacks followed by chronic pain, disability, impaired quality
      of life, and increased mortality. Given their chronic nature, they represent an
      ever more urgent public health problem. MSU and CPP crystals are also able to
      activate nociceptors. The pain in mycrocrystalline arthritis (MCA) is an
      expression of the inflammatory process. In the course of these diseases there is
      an abundant release of inflammatory molecules, including prostaglandins 2 and
      kinins. Interleukin-1 represents the most important cytokine released during the
      crystal-induced inflammatory process. Therefore, clinically, pain is the most
      important component of MCA, which lead to functional impairment and disability in
      a large proportion of the population. It is fundamental to diagnose these
      diseases as early as possible, and to this aim, to identify appropriate and
      specific targets for a timely therapeutic intervention. 

PMID- 24938198
TI  - The sources of pain in osteoarthritis: a pathophysiological review.
AB  - The pain of osteoarthritis (OA) has multifaceted etiologies within and outside
      the joint. It is believed to be driven by both nociceptive and neuropathic
      mechanisms, as well as abnormal excitability in the pain pathways of the
      peripheral and central nervous system. Inflammation in the joint triggers a
      cascade of events that leads to peripheral sensitization, increased sensitivity
      of nociceptive primary afferent neurons, and hyperexcitability of the nociceptive
      neurons in the central nervous system. Pain receptors have been found in the
      synovium, ligaments, capsule, subchondral bone and surrounding tissues, with the
      exception of articular cartilage. The bone-related causes of pain in OA include
      subchondral microfractures, bone stretching with elevation of the periosteum due
      to osteophyte growth, bone remodeling and repair, bone marrow lesions, and bone
      angina caused by decreased blood flow and increased intra-osseous pressure.
      Central factors alter pain processing by setting the gain in such a way that,
      when a peripheral input is present, it is processed against a background of
      central factors that can enhance or diminish the experience of pain. As a complex
      phenomenon with a strong subjective component, pain can also be influenced by the
      nature of the underlying disease, personal predisposition (biological and
      psychological), and environmental and psychosocial factors. This review examines
      the current literature regarding the sources and mechanisms of pain in OA. 

PMID- 24938199
TI  - Pain in fibromyalgia and related conditions.
AB  - Pain is the hallmark symptom of fibromyalgia (FM) and other related syndromes,
      but quite different from that of other rheumatic diseases, which depends on the
      degree of damage or inflammation in peripheral tissues. Sufferers are often
      defined as patients with chronic pain without an underlying mechanistic cause,
      and these syndromes and their symptoms are most appropriately described as
      "central pain", "neuropathic pain", "nonnociceptive pain" or "central sensitivity
      syndromes". The pain is particular, regional or widespread, and mainly relates to
      the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is
      currently considered to be distorted pain or sensory processing, rather than a
      local or regional abnormality. FM is probably the most important and extensively
      described central pain syndrome, but the characteristics and features of FM
      related pain are similar in other disorders of particular interest for
      rheumatologists, such as myofascial pain syndromes and temporo-mandibular joint
      disorders, and there is also an intriguing overlap between FM and benign joint
      hypermobility syndrome. This suggests that the distinctive aspects of pain in
      these idiopathic or functional conditions is caused by central nervous system
      hypersensitivity and abnormalities. Pharmacological and non-pharmacological
      therapies have been suggested for the treatment of these conditions, but a
      multidisciplinary approach is required in order to reduce the abnormal cycle of
      pain amplification and the related maladaptive and self-limiting behaviours. 

PMID- 24938200
TI  - Chronic pelvic pain: comorbidity between chronic musculoskeletal pain and
      vulvodynia.
AB  - Chronic pelvic pain (CPP) is a common condition that has a major impact on the
      quality of life of both men and women. Male CPP is usually attributable to well
      defined urogenital conditions (most frequently infectious/non infectious
      prostatic diseases) or musculoskeletal or bowel diseases, whereas the features of
      female CPP are much more complex and are of particular clinical and
      epidemiological importance. It is a multifactorial syndrome that can be due to
      diseases of the urogenital, gastrointestinal, or musculoskeletal systems, or to
      neurological or neuropsychiatric disorders. It is not always easy to identify its
      predominant pathogenesis, although it often occurs as a central sensitization
      syndrome triggered by an initial stimulus which is no longer detectable and only
      manifests itself clinically through pain. In this respect, there are some very
      interesting relationships between vulvodynia and fibromyalgic syndrome, as
      identified in a preliminary study of women with chronic musculoskeletal pain in
      which it was demonstrated that vulvar pain plays an important role, although it
      is often overlooked and undiagnosed. 

PMID- 24938201
TI  - Anxiety and depression in rheumatologic diseases: the relevance of diagnosis and
      management.
AB  - The high prevalence of emotional disorders (anxiety, chronic stress, mood
      depression) in patients with pain during rheumatologic diseases (particularly
      fibromyalgia) is closely related to the common pathogenic mechanisms concerning
      emotions and pain. Therefore a prompt identification of any psychic component of
      pain, also by means of specific tools, is a must, because it can require an
      adjustment of the therapeutic approach by combining both an analgesic treatment
      and antidepressants and/or psychotherapeutic strategies. 

PMID- 24938202
TI  - Somatoform disorders and rheumatic diseases: from DSM-IV to DSM-V.
AB  - Medically unexplained symptoms are considered 'somatoform disorders' in the
      fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      IV). The introduction of this nosographic category has been helpful in drawing
      attention to a previously neglected area, but has not been successful in
      promoting an understanding of the disorders' biological basis and treatment
      implications, probably because of a series of diagnostic shortcomings. The newly
      proposed DSM-V diagnostic criteria try to overcome the limitations of the DSM-IV
      definition, which was organised centrally around the concept of medically
      unexplained symptoms, by emphasising the extent to which a patient's thoughts,
      feelings and behaviours concerning their somatic symptoms are disproportionate or
      excessive. This change is supported by a growing body of evidence showing that
      psychological and behavioural features play a major role in causing patient
      disability and maintaining high level of health care use. Pain disorders is the
      sub-category of DSM-IV somatoform disorders that most closely resembles
      fibromyalgia. Regardless of the diagnostic changes recently brought about by DSM
      V, neuroimaging studies have identified important components of the mental
      processes associated with a DSM- IV diagnosis of pain disorder. 

PMID- 24938203
TI  - Costs of pain in rheumatology.
AB  - Chronic pain has been identified as an important issue related to various
      rheumatic diseases. At the time of a major government spending review, it is
      appropriate to discuss the pain characterising rheumatic diseases and its related
      costs. It is clearly essential for healthcare authorities to rationalise their
      policies on the basis of the increasing expectations of the users of healthcare
      services while simultaneously balancing their books. There are few published
      studies concerning the costs of pain of any kind, and the same is true of the
      costs of the chronic pain associated with diseases such as rheumatoid arthritis,
      osteoarthritis, and fibromyalgia. 

PMID- 24938204
TI  - Zr(IV) loaded cross-linked chitosan beads with enhanced surface area for the
      removal of nitrate and phosphate.
AB  - In this work, a new method namely silica dissolution method, has been adapted to
      increase the surface area of the cross-linked chitosan beads. Zr(IV) was loaded
      in the cross-linked chitosan beads in order to make it selective for the nitrate
      and phosphate anions from aqueous solutions. Zr(IV) loaded cross-linked chitosan
      beads prepared by normal method (ZrCB) and silica dissolution method (SD-ZrCB)
      were characterised using N2 adsorption/desorption studies, SEM, EDAX, XRD, FTIR,
      TGA, DTA and water regain property. The SD-ZrCB exhibited higher N2 adsorption,
      water regain property as well as anion adsorption capacity than ZrCB. Batch
      method was adapted for the adsorption studies. The nitrate and phosphate adsorbed
      SD-ZrCB was regenerated using 0.025M NaCl solution. There was not much drop in
      adsorption capacities up to 10th regeneration cycle. Freundlich adsorption
      isotherm was the best fit adsorption isotherm among Freundlich, Langmuir and
      Dubinin-Radushkevich (D-R) isotherms which have been used to fit the nitrate and
      phosphate adsorption data. Thermodynamic parameters such as DeltaG degrees ,
      DeltaH degrees  and DeltaS degrees  were calculated in order to understand the
      nature of adsorption process. 

PMID- 24938205
TI  - In vitro selection and identification of ssDNA aptamers recognizing the Ras
      protein.
AB  - The aim of this study was to develop high-affinity single-stranded DNA (ssDNA)
      aptamers that can selectively recognize the protein Ras and can be used as
      preventive and therapeutic agents for restenosis occurring after coronary surgery
      or angioplasty. For this purpose, we used the systematic evolution of ligands by
      exponential enrichment (SELEX) technique, also known as in vitro selection. Using
      this technique, ssDNA aptamers recognizing the Ras protein were obtained from a
      synthesized random ssDNA library in vitro. The binding rate and affinity of each
      aptamer pool, isolated in successive rounds of selection, were measured using
      ELISA, and the finally selected aptamer pool was cloned and sequenced. The
      binding affinities of each aptamer in this pool were measured. Their primary and
      secondary structures were analyzed using the DNAMAN 5.29 software, and the
      relationship between these structures and corresponding binding affinities was
      analyzed. The rate of aptamer pool binding to the Ras protein gradually increased
      from 2.4 to 34.5% along the selection process. Optical density (OD) and
      equilibrium dissociation constant (Kd) measurements showed that OD gradually
      increased from 0.220 to 1.080 and Kd decreased from 51.5 to 18.3 nM. The 11th
      pool of aptamers was selected based on these analyses, and cloning and sequencing
      of individual aptamers was performed. Secondary structure analysis revealed
      different conformations, but of a single type: stem-loop. The aptamer Ra1 showed
      the highest affinity, with a measured OD of 1.213 and an estimated Kd of 15.3 nM.
      The binding affinity of the aptamer Ra1 to Ras was dose-dependent. In conclusion,
      high-affinity ssDNA aptamers recognizing the Ras protein have been successfully
      selected. These aptamers may serve in the future as preventive and/or therapeutic
      agents for restenosis occurring after coronary surgery or angioplasty.

PMID- 24938207
TI  - Computational insights into the binding mechanism of antagonists with
      neuropeptide B/W receptor 1.
AB  - Neuropeptide B/W receptor 1 (NPBWR1), previously known as G-protein coupled
      receptor 7 (GPR7), is a class A G-protein coupled receptor implicated in the
      modulation of several neuroendocrine functions such as feeding behavior, energy
      homeostasis, epilepsy, and analgesia. In recent years, a few antagonists have
      been designed that bind to NPBWR1 with high affinity. However, the exact binding
      modes between the antagonists and the receptor are still unknown. Unraveling the
      key pharmacophoric features of the receptor will guide the development of novel
      compounds with increased potency for therapeutic use. Here, we studied the
      structural organization of NPBWR1 receptor and its antagonist binding modes
      through computational approaches. Based on the dynamics and energetic features of
      receptor-ligand interactions, we categorized the binding affinities of the
      antagonists for NPBWR1 and identified key residues responsible for ligand
      recognition by NPBWR1. Binding free energy calculations revealed that the
      residues Trp102(ECL1), Val113(3.29), Gln281(ECL3), and Ala274(6.58) were crucial
      for ligand interaction. The results of our study will be useful to understand the
      structure-function relationship of NPBWR1 that may assist future drug discovery
      initiatives. 

PMID- 24938206
TI  - Influence of catalyst structure and reaction conditions on anti- versus syn
      aminopalladation pathways in Pd-catalyzed alkene carboamination reactions of N
      allylsulfamides.
AB  - The Pd-catalyzed coupling of N-allylsulfamides with aryl and alkenyl triflates to
      afford cyclic sulfamide products is described. In contrast to other known Pd
      catalyzed alkene carboamination reactions, these transformations may be
      selectively induced to occur by way of either anti- or syn-aminopalladation
      mechanistic pathways by modifying the catalyst structure and reaction conditions.

PMID- 24938208
TI  - The rolC gene increases caffeoylquinic acid production in transformed artichoke
      cells.
AB  - Caffeoylquinic acids are found in artichokes, and they are currently considered
      important therapeutic or preventive agents for treating Alzheimer's disease and
      diabetes. We transformed artichoke [the cultivated cardoon or Cynara cardunculus
      var. altilis DC (Asteraceae)] with the rolC gene, which is a known inducer of
      secondary metabolism. High-performance liquid chromatography with UV and high
      resolution mass spectrometry (HPLC-UV-HRMS) revealed that the predominant
      metabolites synthesized in the transgenic calli were 1,5-dicaffeoylquinic acid,
      3,4-dicaffeoylquinic acid, and chlorogenic acid. The rolC-transformed calli
      contained 1.5% caffeoylquinic acids by dry weight. The overall production of
      these metabolites was three times higher than that of the corresponding control
      calli. The enhancing effect of rolC remained stable over long-term cultivation.

PMID- 24938209
TI  - Induction and carbon catabolite repression of phenol degradation genes in
      Rhodococcus erythropolis and Rhodococcus jostii.
AB  - Rhodococcus erythropolis CCM2595 is able to efficiently utilize phenol and other
      aromatic compounds. We cloned and sequenced its complete gene cluster - catA,
      catB, catC, catR, pheR, pheA2, pheA1 - involved in the ortho-cleavage pathway of
      phenol. The activity of the key enzyme of the phenol degradation pathway, two
      component phenol hydroxylase, was found to be induced by phenol. When both phenol
      and succinate were present in the medium, phenol hydroxylase activity decreased
      substantially. To analyze the regulation of phenol degradation at the
      transcriptional level, the transcriptional fusions of the divergently oriented
      promoters PpheA2 and PpheR with the gfpuv reporter gene were constructed. The
      promoters driving expression of the genes of the pheR-pheA2pheA1 cluster were
      localized by determining the respective transcriptional start points.
      Measurements of GFP fluorescence as well as quantitative RT-PCR revealed that
      expression of the phe genes is induced by phenol at the transcriptional level.
      The transcription of pheA2A1 and pheR was repressed by succinate, whereas no
      repression by glucose or glycerol was observed. Activation of the R. erythropolis
      CCM2595 pheA2 promoter by PheR, an AraC-type transcriptional regulator, was
      demonstrated by overexpression of the pheR gene. Analysis of the transcriptional
      regulation of two similar phe clusters from R. jostii RHA1 by various substrates
      showed that the type of carbon catabolite repression and the temporal
      transcriptional pattern during cultivation are different in each of the three phe
      clusters analyzed. 

PMID- 24938211
TI  - A 2,6-bis(phenylamino)pyridinato titanium catalyst for the highly regioselective
      hydroaminoalkylation of styrenes and 1,3-butadienes.
AB  - The C-C bond forming catalytic hydroaminoalkylation of terminal alkenes, 1,3
      dienes, or styrenes allows a direct and highly atom efficient (100 %) synthesis
      of amines which can result in the formation of two regioisomers, the linear and
      the branched product. We present a new titanium catalyst with 2,6
      bis(phenylamino)pyridinato ligands for intermolecular hydroaminoalkylation
      reactions of styrenes and 1-phenyl-1,3-butadienes that delivers the corresponding
      linear hydroaminoalkylation products with excellent regioselectivities.

PMID- 24938213
TI  - The promises and pitfalls of genetic epidemiologic approaches to pediatric
      cancers: lessons from MDM2.

PMID- 24938212
TI  - The impact of chronic physical illness, maternal depressive symptoms, family
      functioning, and self-esteem on symptoms of anxiety and depression in children.
AB  - The present study extends earlier research identifying an increased risk of
      anxiety among children with chronic physical illness (CwCPI) by examining a more
      complete model that explains how physical illness leads to increased symptoms of
      anxiety and depression. We tested a stress-generation model linking chronic
      physical illness to symptoms of anxiety and depression in a population-based
      sample of children aged 10 to 15 years. We hypothesized that having a chronic
      physical illness would be associated with more symptoms of anxiety and
      depression, increased levels of maternal depressive symptoms, more family
      dysfunction, and lower self-esteem; and, that maternal depressive symptoms,
      family dysfunction, and child self-esteem would mediate the influence of chronic
      physical illness on symptoms of anxiety and depression. Data came from the
      National Longitudinal Survey of Children and Youth (N = 10,646). Mediating
      processes were analyzed using latent growth curve modeling. Childhood chronic
      physical illness was associated with increases in symptoms of anxiety and
      depression, beta = 0.20, p < 0.001. Mediating effects were also observed such
      that chronic physical illness resulted in increases in symptoms of maternal
      depression and family dysfunction, leading to declines in child self-esteem, and
      in turn, increases in symptoms of anxiety and depression. CwCPI are at-risk for
      symptoms of anxiety and depression. Some of this elevated risk appears to work
      through family processes and child self-esteem. This study supports the use of
      family-centered care approaches among CwCPI to minimize burden on families and
      promote healthy psychological development for children.

PMID- 24938214
TI  - Childhood anxiety trajectories and adolescent disordered eating: findings from
      the NICHD Study of Early Child Care and Youth Development.
AB  - OBJECTIVE: The goal of the present article was to examine whether childhood
      anxiety trajectories predict eating psychopathology. We predicted that girls with
      trajectories of increasing anxiety across childhood would have significantly
      greater risk of disordered eating in adolescence in comparison to girls with
      stable or decreasing trajectories of anxiety over childhood. METHOD: Data were
      collected as part of the prospective longitudinal NICHD Study of Early Child Care
      and Youth Development (N = 450 girls). Childhood anxiety was assessed yearly (54
      months through 6th grade) via maternal report on the Child Behavior Checklist.
      Disordered eating behaviors were assessed at age 15 via adolescent self-report on
      the Eating Attitudes Test (EAT-26). We conducted latent growth mixture modeling
      to define girls' childhood anxiety trajectories. Maternal sensitivity, maternal
      postpartum depression, maternal anxiety, and child temperament were included as
      predictors of trajectory membership. RESULTS: The best fitting model included
      three trajectories of childhood anxiety, the low-decreasing class (22.9% of
      girls), the high-increasing class (35.4%), and the high-decreasing class (41.6%).
      Mothers with more symptoms of depression and separation anxiety had girls who
      were significantly more likely to belong to the high-increasing anxiety
      trajectory. There were no significant differences in adolescent disordered eating
      for girls across the three childhood anxiety trajectories. DISCUSSION: Childhood
      anxiety, as captured by maternal report, may not be the most robust predictor of
      adolescent disordered eating and may be of limited utility for prevention
      programs that aim to identify children in the community at greatest risk for
      disordered eating.

PMID- 24938217
TI  - Bicuspid aortic valve endocarditis complicated by ruptured sinus of Valsalva
      aneurysm.

PMID- 24938215
TI  - Creativity and neurological disease.
AB  - Although humans have long valued creativity, the generation of such innovation is
      still incompletely understood. Looking at the healthy brain, researchers have
      localized certain parts for a basic understanding of these mechanisms. By
      researching the brain affected by neurological disease, scientists have observed
      unique manifestations of creativity, such as in frontotemporal lobar
      degeneration, Alzheimer's disease, Parkinson's disease and parkinsonian spectrum
      disorders, and stroke, which help clarify these creative underpinnings.
      Incorporating both healthy and disease models of cerebral functioning,
      neurological and neuroscientific research from recent years has built on
      established theories and expanded current knowledge.

PMID- 24938216
TI  - Update on HIV dementia and HIV-associated neurocognitive disorders.
AB  - The introduction of combined antiretroviral therapy (cART) has dramatically
      reduced the risk of central nervous system opportunistic infection and severe
      dementia secondary to HIV infection in the last two decades. However, a milder
      form of HIV-associated neurocognitive disorder (HAND) remains prevalent in the
      cART era and has a significant impact on patients' quality of life. In this
      review, we outline updated research findings on investigating and monitoring
      cognitive impairment in HAND patients. The outcomes of recent research on the
      pathogenesis of HAND and how it overlaps with neurodegenerative diseases are
      discussed. Lastly, there is a brief discussion of the results of clinical trials
      using a brain-penetrating cART regimen.

PMID- 24938218
TI  - Recurrent syncope associated with idiopathic jugular vein stenosis. Report of a
      young female patient.

PMID- 24938219
TI  - Right ventricular and atrial functions in systemic sclerosis patients without
      pulmonary hypertension. Speckle-tracking echocardiographic study.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a systemic connective tissue disease and
      cardiac involvement is one of the most important causes of death. Right
      ventricular (RV) systolic dysfunction is a poor prognostic finding in SSc
      patients. Assessment of RV function has some difficulties because of its crescent
      shape and extensive trabeculations. Two-dimensional (2D) speckle-tracking
      echocardiography (STE) is an angle-independent quantitative technique to evaluate
      myocardial function. The aim of this study was to assess the RV and right atrial
      (RA) functions of SSc patients without pulmonary hypertension by using 2D STE.
      PATIENTS AND METHODS: A total of 40 patients with SSc (mean age 48.5 +/- 11.4
      years, 28 female) and 40 healthy volunteers (mean age 45.9 +/- 7.6 years, 21
      female) were included in the study. All subjects underwent transthoracic
      echocardiography for evaluation of RV and RA functions with 2D STE. RESULTS:
      Although left ventricular systolic and diastolic functions, systolic pulmonary
      artery pressure (PAP), and RA measurements were similar in both groups, tricuspid
      annular plane systolic excursion (TAPSE) and maximum systolic myocardial velocity
      (S') were decreased in SSc patients. The RV free wall global longitudinal strain
      (GLS) of SSc patients was lower than the controls (- 18.5 +/- 4.9 % vs. - 21.8 +/
      2.4 %, p < 0.001) and the RA reservoir and conduit functions were also decreased
      in SSc patients compared with controls (34.4 +/- 9.9 % vs. 39.7 +/- 11.2 %, p =
      0.027 and 15.0 +/- 5.7 % vs. 18.7 +/- 6.4 %, p = 0.009, respectively). Disease
      duration was inversely correlated with RVGLS and TAPSE (r: - 0.416, p = 0.018 and
      r: - 0.383, p = 0.031, respectively). CONCLUSION: The use of 2D STE can be
      helpful in the detection of impairment in RV and RA functions in SSc patients
      with normal PAP.

PMID- 24938221
TI  - DFT calculations on kinetic data for some [4+2] reactions in solution.
AB  - The reaction mechanisms of [4+2] cycloaddition reactions between dienes and
      dienophiles have been investigated with several density functional theory (DFT)
      methods, such as CAM-B3LYP, BMK, M062x wB97x and wB97xd, and the obtained results
      show that most of the reactions are synchronous or asynchronous. The stability of
      the transition state is moderated by the interaction of frontier molecular
      orbitals (FMOs), in which a diene acts as an electron-donating partner and a
      dienophile acts as an electron-acceptor from the charge transfer direction in the
      transition state. The activation free energy barriers have been calculated with
      both gas-phase translational entropy and solution translational entropy, in which
      those from gas-phase translational entropy (output of the Gaussian job) are far
      away from the experimental estimations. It has been found that free-energy
      barriers generated from solution translational entropies with CAM-B3LYP+IDSCRF/6
      31G(d), BMK+IDSCRF/6-31G(d) and wB97x+IDSCRF/6-31G(d) are very close to the
      experimental measurements, but both M062x and wB97xd methods predict too low free
      energy barriers for most of the studied reactions. The substituent and solvent
      effects on reaction dynamic data have also been addressed. 

PMID- 24938220
TI  - Suspected inflammatory cardiomyopathy. Prevalence of Borrelia burgdorferi in
      endomyocardial biopsies with positive serological evidence.
AB  - BACKGROUND: Cardiac involvement in Lyme disease, caused by the tick-borne
      spirochete Borrelia burgdorferi, has been reported to occur in 0.3-4 % of
      infected patients in Europe. Cardiac manifestations may include conduction
      disturbances, and also myocarditis, pericarditis, and left ventricular
      dysfunction. We investigated the prevalence of B. burgdorferi DNA in
      endomyocardial biopsies from patients with suspected inflammatory heart disease
      and positive serology for B. burgdorferi. METHODS AND RESULTS: In 64 patients,
      endomyocardial biopsies were taken after exclusion of coronary heart disease by
      coronary angiography, and investigated with polymerase chain reaction (PCR) for
      the presence of B. burgdorferi and cardiotropic viruses. B. burgdorferi DNA was
      not detected in any of the endomyocardial biopsies. Viruses, particularly
      parvovirus B19, were detected as infectious agents in 19 (30 %) patients.
      CONCLUSION: The results of our study demonstrate that PCR analysis of
      endomyocardial biopsies from patients with suspected inflammatory heart disease,
      including individuals with dilated cardiomyopathy (DCM) and positive serology for
      B. burgdorferi, did not reveal the B. burgdorferi genome in any biopsy sample.

PMID- 24938210
TI  - Developmental consequences of fetal exposure to drugs: what we know and what we
      still must learn.
AB  - Most drugs of abuse easily cross the placenta and can affect fetal brain
      development. In utero exposures to drugs thus can have long-lasting implications
      for brain structure and function. These effects on the developing nervous system,
      before homeostatic regulatory mechanisms are properly calibrated, often differ
      from their effects on mature systems. In this review, we describe current
      knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates
      (among other drugs) produce alterations in neurodevelopmental trajectory. We
      focus both on animal models and available clinical and imaging data from cross
      sectional and longitudinal human studies. Early studies of fetal exposures
      focused on classic teratological methods that are insufficient for revealing more
      subtle effects that are nevertheless very behaviorally relevant. Modern
      mechanistic approaches have informed us greatly as to how to potentially
      ameliorate the induced deficits in brain formation and function, but conclude
      that better delineation of sensitive periods, dose-response relationships, and
      long-term longitudinal studies assessing future risk of offspring to exhibit
      learning disabilities, mental health disorders, and limited neural adaptations
      are crucial to limit the societal impact of these exposures. 

PMID- 24938222
TI  - Sensitivity improvement in fluorescence-based particle detection.
AB  - Microfluidic flow cytometers are highly interesting candidates for biomedical
      point-of-care applications. However, the sensitivity, reliability, and throughput
      of these systems must be improved to provide the full functionality of
      established flow cytometric systems. One proposed method to improve fluorescence
      detection systems is to use spatial modulation techniques. We derive the noise
      related statistics and calculate the coefficient of variation for a detection
      system with and without spatial modulation. We measure the noise properties of a
      nonmodulated microfluidic fluorescence particle detection system and analyze the
      possible performance gains using spatial modulation.

PMID- 24938223
TI  - Vanadium-controlled crystallization of stereoisomers of NBu4[VO2(N-salicylidene
      isoleucinato)] through epimerization.
AB  - Reported herein is a simple synthetic and crystallization procedure for
      sequential isolation of two stereoisomers of isoleucine-derived vanadium(V)
      complexes from a racemic mixture with three stereogenic centers and therefore
      eight hypothetical species. The products of this crystallization were
      characterized by electronic and vibrational circular dichroism, NMR spectroscopy,
      and polarimetry to compare the chiroptic properties of the enantiomerically pure
      analogues prepared from L-isoleucine and D-allo-isoleucine. NMR studies pointed
      to the yet unobserved phenomenon of vanadium-catalyzed epimerization of
      isoleucine. 

PMID- 24938224
TI  - The HYPERFlax trial for determining the anti-HYPERtensive effects of dietary
      flaxseed in newly diagnosed stage 1 hypertensive patients: study protocol for a
      randomized, double-blinded, controlled clinical trial.
AB  - BACKGROUND: In 2013 the World Health Organization deemed hypertension as a global
      crisis as it is the leading risk factor attributed to global mortality.
      Therefore, there is a great need for effective alternative treatment strategies
      to combat a condition that affects 40% of adults worldwide. Recently, the FlaxPAD
      Trial observed a significant reduction in systolic and diastolic blood pressure
      in hypertensive patients with peripheral arterial disease that consumed 30 g of
      milled flaxseed per day for one year. However, these patients were already on
      anti-hypertensive medication. Therefore, there is a need to assess if dietary
      flaxseed can effectively reduce blood pressure in the absence of peripheral
      arterial disease and anti-hypertensive medication in newly diagnosed hypertensive
      patients. METHODS/DESIGN: The HYPERFlax Trial is a parallel, superiority, phase
      II/III, randomized, double-blinded, controlled clinical trial. St. Boniface
      Hospital and the Health Sciences Centre of Winnipeg, Canada, will recruit 100
      participants newly diagnosed with stage 1 hypertension who have yet to be
      administered anti-hypertensive medication. Participants will be randomly
      allocated with a 1:1 ratio into a flaxseed or control group and provided food
      products to consume daily for six months. At baseline, two, four, and six months,
      participant assessments will include the primary outcome measure, averaged
      automated blood pressure, and secondary measures: 24-hour food recall,
      international physical activity questionnaire, anthropometrics, and blood and
      urine sampling for biochemical analysis. Plasma will be assessed for lipids,
      metabolomics profiling, and molecules that regulate vascular tone. Urine will be
      collected for metabolomics profiling. With an estimated dropout rate of 20%, the
      trial will have a power of 0.80 to detect differences between groups and across
      time, out of an effect size of 0.7 (SD) at an alpha level of 0.05. DISCUSSION:
      This trial will determine if dietary flaxseed is efficacious over six months as
      an anti-hypertensive therapy in subjects newly diagnosed with hypertension. If
      flaxseed can effectively reduce blood pressure as a monotherapy, then flaxseed
      will provide individuals on a global basis with a cost-effective food-based
      strategy to control hypertension. TRIAL REGISTRATION: NCT01952340, Registered 24
      September 2013.

PMID- 24938225
TI  - Activation of multiple transcriptional regulators by growth restriction in
      Pseudomonas aeruginosa.
AB  - Growth restriction by antibiotics is a common feature that pathogenic bacteria
      must overcome for survival. The struggle of bacteria to escape from growth
      restriction eventually results in development of antibiotic-resistance through
      the expression of a set of genes. Here we found that some physiologically
      important transcriptional regulators of Pseudomonas aeruginosa including QscR, a
      quorum sensing (QS) receptor, SoxR, a superoxide sensor-regulator, and AntR, a
      regulator of anthranilate-related secondary metabolism, are activated by various
      growth-restricted conditions. We generated the growth-restricted conditions by
      various methods, such as overexpression of PA2537 and treatment with antibiotics
      or disinfectants. The overexpression of PA2537, encoding an acyltransferase
      homologue, tightly restricted the growth of P. aeruginosa and significantly
      activated QscR during the growth restriction. Similarly, treatments with
      gentamycin, tetracycline, and ethanol also activated QscR near their minimal
      inhibitory concentrations (MICs). Some non-QS regulators, such as AntR and SoxR,
      were also activated near the MICs in the same conditions. However, LasR and PqsR,
      other QS receptors of P. aeruginosa, were not activated, suggesting that only a
      specific set of transcriptional regulators is activated by growth restriction.
      Since paraquat, a super-oxide generator, significantly activated QscR and AntR,
      we suggest that the oxidative stress generated by growth restriction may be
      partly involved in this phenomenon. 

PMID- 24938226
TI  - Effect of body mass index on global DNA methylation in healthy Korean women.
AB  - Obesity is known to be strongly associated with cardiovascular disease and
      cancer, the leading causes of mortality worldwide, and develops owing to
      interactions between genes and the environment. DNA methylation can act as a
      downstream effector of environmental signals, and analysis of this process
      therefore holds substantial promise for identifying mechanisms through which
      genetic and environmental factors jointly contribute to disease risk. Global DNA
      methylation of peripheral blood cells has recently been proposed as a potential
      biomarker for disease risk. Repetitive element DNA methylation has been shown to
      be associated with prominent obesity-related chronic diseases, but little is
      known about its relationship with weight status. In this study, we quantified the
      methylation of Alu elements in the peripheral blood DNA of 244 healthy women with
      a range of body mass indexes (BMIs) using pyrosequencing technology. Among the
      study participants, certain clinical laboratory parameters, including hemoglobin,
      serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase,
      total cholesterol, and triglyceride levels were found to be strongly associated
      with BMI. Moreover, a U-shaped association between BMI and Alu methylation was
      observed, with the lowest methylation levels occurring at BMIs of between 23 and
      30 kg/m(2). However, there was no significant association between Alu methylation
      and age, smoking status, or alcohol consumption. Overall, we identified a
      differential influence of BMI on global DNA methylation in healthy Korean women,
      indicating that BMI-related changes in Alu methylation might play a complex role
      in the etiology and pathogenesis of obesity. Further studies are required to
      elucidate the mechanisms underlying this relationship. 

PMID- 24938227
TI  - Monitoring the differentiation and migration patterns of neural cells derived
      from human embryonic stem cells using a microfluidic culture system.
AB  - Microfluidics can provide unique experimental tools to visualize the development
      of neural structures within a microscale device, which is followed by guidance of
      neurite growth in the axonal isolation compartment. We utilized microfluidics
      technology to monitor the differentiation and migration of neural cells derived
      from human embryonic stem cells (hESCs). We co-cultured hESCs with PA6 stromal
      cells, and isolated neural rosette-like structures, which subsequently formed
      neurospheres in suspension culture. Tuj1-positive neural cells, but not nestin
      positive neural precursor cells (NPCs), were able to enter the microfluidics
      grooves (microchannels), suggesting that neural cell-migratory capacity was
      dependent upon neuronal differentiation stage. We also showed that bundles of
      axons formed and extended into the microchannels. Taken together, these results
      demonstrated that microfluidics technology can provide useful tools to study
      neurite outgrowth and axon guidance of neural cells, which are derived from human
      embryonic stem cells. 

PMID- 24938228
TI  - Nuclease delivery: versatile functions of SLX4/FANCP in genome maintenance.
AB  - As a scaffold, SLX4/FANCP interacts with multiple proteins involved in genome
      integrity. Although not having recognizable catalytic domains, SLX4 participates
      in diverse genome maintenance pathways by delivering nucleases where they are
      needed, and promoting their cooperative execution to prevent genomic
      instabilities. Physiological importance of SLX4 is emphasized by the
      identification of causative mutations of SLX4 genes in patients diagnosed with
      Fanconi anemia (FA), a rare recessive genetic disorder characterized by genomic
      instability and predisposition to cancers. Recent progress in understanding
      functional roles of SLX4 has greatly expanded our knowledge in the repair of DNA
      interstrand crosslinks (ICLs), Holliday junction (HJ) resolution, telomere
      homeostasis and regulation of DNA damage response induced by replication stress.
      Here, these diverse functions of SLX4 are reviewed in detail. 

PMID- 24938231
TI  - A new field-of-view autotracking method for online tomography reconstruction
      based on back-projected ray image cross-correlation.
AB  - We devised a new field-of-view autotracking method for online tomography
      reconstruction based on a cross-correlation between a pair of neighbours, called
      back-projected ray images, among a specimen tilt sequence. One ray image is
      calculated through normal filtered back-projection only in the cross-sectional
      plane from each projection image. This ray-image matching can reliably track the
      field-of-view because a pair of neighbouring ray images mostly cross-correlates
      at the existing three-dimensional object position. Online experiments using real
      specimens resulted in successful autotracking performance with high accuracy, and
      online tomograms were obtained immediately after the final tracking at the last
      tilting angle. 

PMID- 24938232
TI  - [Epidomiological characteristics of infective endocarditis: a study of 135
      cases].
AB  - BACKGROUND: Infective endocarditis (IE) is a serious pathology which is in a
      continuum evolution in the setting of diagnosis and therapeutic fields AIM: To
      describe clinical, echocardiographic, microbiological, therapeutic and outcome
      characteristics of infective endocarditis in a Tunisian population. METHODS: The
      records of 135 patients admitted to adult cardiology department of la Rabta
      hospital between January 1981 and December 2011 were collected. The diagnosis of
      certain IE was retained according to modified Duke Criteria. RESULTS: The mean
      age of patients was 38.5 +/- 16 years, with a male predominance (sex ratio: 1.4).
      IE affected native valves in 77% of cases, prosthetic valve in 15.5% of cases,
      congenital heart disease in 2% and pacemaker in 1.48% of patients. The portal of
      entry was identified in 43.7% of the patients, the oral origin was predominant.
      Blood cultures were positive in only 34% of patients. Causative microorganism was
      staphylococcus in 43.6%, streptococcus in 43.6% and negative bacill gram in 17.4%
      of patients. Echocardiography showed vegetation in 98% of patients, cardiac
      abscess in 23.7% of patients and valve mutilation in 17.7% of cases. Prosthesis
      dehiscence was present in 4.5% of cases. Complications were primarily hemodynamic
      (57%) followed by embolic events (34%). Surgery occurred in 57.7% of patients, it
      was early in 69% of cases. The indication was mainly hemodynamic and mixed in
      70%of patients. Hospital mortality was 28% with predictor's factors: left heart
      (p=0.02), prosthesis (p <0.05), staphylococcus (p<0.005), heart failure (p<0.05)
      and neurological complications (p=0.04). CONCLUSION: According to our study,
      infective endocarditis has always touched a young population in Tunisia,
      rheumatic valve disease is still the predominant underlying heart disease and
      both streptococcus and staphylococcus are most frequently isolated. Mortality
      remains high despite considerable progress in terms of diagnosis and therapy.

PMID- 24938229
TI  - Hypoxia-induced endothelial progenitor cell function is blunted in
      angiotensinogen knockout mice.
AB  - Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in
      tumor angiogenesis and associated with the pathogenesis of coronary
      atherosclerosis. This study was undertaken to determine the role played by AGT in
      endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was
      found that the number of EPC colonies formed by AGT heterozygous knockout (AGT(+/
      )) cells was less than that formed by wild-type (WT) cells, and that the
      migration and tube formation abilities of AGT(+/-) EPCs were significantly lower
      than those of WT EPCs. In addition, the gene expressions of vascular endothelial
      growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived
      factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial
      nitric oxide synthase (eNOS) were suppressed in AGT(+/-) EPCs. Furthermore, the
      expressions of hypoxia-inducible factor (HIF)-1alpha and -2alpha were
      downregulated in AGT(+/-) early EPCs under hypoxic conditions, suggesting a
      blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling
      pathways induced by VEGF, epithelial growth factor (EGF), or SDF-1alpha were
      suppressed in AGT(+/-) EPCs. In AGT(+/-) mice, the incorporation of EPCs into the
      tumor vasculature was significantly reduced, and lung tumor growth and melanoma
      metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced
      vasculogenesis. 

PMID- 24938233
TI  - [Primary biliary cirrhosis: a retrospective study of 36 cases].
AB  - BACKGROUND: Primary biliary cirrhosis is a rare cholestasis liver disease
      affecting the women of mature age,it association with Autoimmune hepatitis
      defined the overlap syndrome. AIM: It was to determine epidemiological, clinic
      biological, immunological, histological, therapeutic and evolutive
      characteristics of PBC and to compare them to those in subjects having an overlap
      syndrome. METHODS: It is a retrospective study grouping all the cases of PBC
      hospitalized over a period of 15 years (1995-2009) in the hepatogastro-enterology
      department at Sahloul hospital in Sousse. RESULTS: Thirty six cases were grouped
      over the period of the study. They were all women. The mean age was 54.5 years
      (28-79). The disease was symptomatic at the moment of diagnosis in 75% of the
      cases. The functional signs revealing the disease were principally asthenia,
      present in 69.4% of the cases, followed by jaundice and prurit. Cholestasis was
      constant in all the patients, stage III of scheuer was the most frequent in the
      patients (25%) followed by stage IV (22%). OS was present in 1/3 of the patients;
      the treatment is based on the prescription of urso-desoxycholic Acid associated
      with corticoids and with immunosuppressors in the case of OS. The average
      survival of the patient having PBC and OS was comparable. It was respectively of
      61.8 and 55.9 months. CONCLUSION: Our results as well as the literature reveal
      the rarety of this disease and its predominance in women. PBC has to be diagnosed
      at an early stage to guarantee a better response and a better survival of the
      patients.

PMID- 24938234
TI  - [The morbidity diagnosed among the elderly in primary care at the sanitary region
      of Sousse].
AB  - BACKGROUND: Nowadays, the ageing of the population became a societal frequent
      problem throughout the world. In Tunisia, the part of the elderly of 60 years old
      and over is estimated at 17,7 % in 2029. This ageing is at the origin of
      important health problems, in particular the increase of the frequency of the
      chronic diseases. AIM: To identify the Sociodemographic characteristics of the
      consultants of 65 years old and over, and to describe the morbidity diagnosed in
      this age group in the primary health care centers of the sanitary region of
      Sousse. METHODS: We conducted a cross-sectional descriptive study in 86 primary
      health care centers in Sousse over 1 year (2002-2003). Medical records for 3
      weeks per season were randomly selected. The International Classification of
      Primary Care (ICPC) was used to code recorded data. RESULTS: 2198 consultations
      were collected, elderly person presents on average 1,22 (+/- 0,55) morbid states
      by consultation. The main diseases identified in order were cardiovascular
      (26,2%), breathing (20,8%), osteo-articular (14,8%). Psychological and social
      disorders accounted for only 0,4% of cases. The major health problems were
      uncomplicated hypertension (22,4%), acute bronchitis / bronchiolitis (9,2%),
      diabetes mellitus type 2 (7,9%) and osteoarthritis of knee (4,7%). CONCLUSION:
      These results are important both to meet the needs of consultants and especially
      to better adapt the training to practice field.

PMID- 24938230
TI  - Strategies for improving potassium use efficiency in plants.
AB  - Potassium is a macronutrient that is crucial for healthy plant growth. Potassium
      availability, however, is often limited in agricultural fields and thus crop
      yields and quality are reduced. Therefore, improving the efficiency of potassium
      uptake and transport, as well as its utilization, in plants is important for
      agricultural sustainability. This review summarizes the current knowledge on the
      molecular mechanisms involved in potassium uptake and transport in plants, and
      the molecular response of plants to different levels of potassium availability.
      Based on this information, four strategies for improving potassium use efficiency
      in plants are proposed; 1) increased root volume, 2) increasing efficiency of
      potassium uptake from the soil and translocation in planta, 3) increasing
      mobility of potassium in soil, and 4) molecular breeding new varieties with
      greater potassium efficiency through marker assisted selection which will require
      identification and utilization of potassium associated quantitative trait loci. 

PMID- 24938235
TI  - Appropiateness of colonoscopy in the university hospital center of monastir.
      Interest and applicability of criteria established by the European panel on the
      appropriateness of gastrointestinal endoscopy.
AB  - AIM: 1) To assess the applicability of EPAGE criteria in there first version
      (EPAGE I) in clinical practice, 2) to assess colonoscopy appropriateness using
      EPAGE I criteria, 3) to compare colonoscopy appropriateness and findings.
      METHODS: Four hundred and eighty-seven consecutive diagnostic colonoscopies were
      included. The appropriateness of the indication of colonoscopy was appreciated
      using a scoring system on the basis of the EPAGE criteria in there first version
      (EPAGE I). RESULTS: Appropriateness were applied in 86,4% of the colonoscopies.
      Fifty-one percent were appropriate, 14% uncertain and 18% inappropriate. The
      difference of 17% represented the procedures indicated for hematochezia and for
      witch an appropriateness score can not be attributed because of lack of clinical
      information. The probability of finding a clinically significant lesion was
      significantly higher in patients aged >= 50 years, males, inpatients, those
      referred by gastroenterologists and those who had the colonoscopy for
      "appropriate" indication according to the EPAGE I criteria. The independent
      variables correlated with the diagnostic yield of colonoscopy were the age, the
      appropriateness of indication and the health care setting. CONCLUSION: EPAGE I
      criteria were applicable in most patients and were correlated with significant
      findings. They are thereby useful to rationalize colonoscopy demand. However,
      they could be regularly updated.

PMID- 24938236
TI  - [Bacterial meningitis in children: epidemiological data and outcome].
AB  - BACKGROUND: The bacterial meningitis in children remains a worrisome affection
      both by its frequency and by its gravity. AIM: describe the epidemiological,
      clinical and evolutionary data of bacterial meningitis in children aged between 3
      months and 15 years. METHODS: we conducted a retrospective study of all cases of
      bacterial meningitis collected in the department of pediatrics of Hedi Chaker
      hospital, during a period of 6 years (2006-2011). We analyzed the files
      retrospectively and we studied the epidemiological data and the outcome. RESULTS:
      Thirty cases of bacterial meningitis were recorded. The most frequent species
      were Streptococcus pneumoniae and Haemophilus influenzae followed by Neisseria
      meningitidis with respectively 43%, 40%, and 6% of cases. The yearly distribution
      of these bacteria showed an increase of the rate of the bacterial meningitis
      during the last 2 years. The average age of our patients was 1 year 6months (3
      months-13 years). All the patients were vaccinated according to the Tunisian
      vaccination calendar; and none of them had pneumococcal vaccine or the Hib
      vaccine. The main clinical manifestations were fever (100 %), seizures (14 %) and
      vomiting (44 %). Bulging fontanel was noted in 15cas (55 %), somnolence in 11
      cases (40 %) and axial hypotonia in 12 cases (44 %). In the outcome, the
      neurological sequelae were showed in eight patients (26%). CONCLUSION: In our
      study, H. influenzae and S. pneumoniae were the main microorganisms responsible
      for bacterial meningitis. We strongly recommend the introduction pneumococcal
      vaccine in our vaccination calendar.

PMID- 24938237
TI  - [Evaluation of fibrinolysis with streptokinase in ST-elevation myocardial
      infarction admitted to emergency department].
AB  - BACKGROUND: Fibrinolysis during ST elevation myocardial infarction (STEMI) is
      feasible in the emergency departments (ED), and this reduces the delay from first
      medical contact to coronary reperfusion. The aim of the study is to: 1) Evaluate
      fibrinolysis with streptokinase (SK) in STEMI admitted to the ED. 2) identify
      clinical criteria predictive of fibrinolysis success. METHODS: prospective study
      (July 2008-March 2012). Inclusion of STEMI thrombolysed by SK. Fibrinolysis
      success was defined according to clinical and Electrocardiogram criteria.
      Multivariate study is used to identify the factors associated with thrombolysis
      success. RESULTS: Out of the 329 STEMI enrolled during the study period, 224
      (68%) were thrombolysed. Mean age = 57 +/- 11 years (20-86 years) sex ratio = 6.
      The average time chest pain - emergency admission was 195 +/- 177 min (15 min to
      12 hours). The 2/3 of patients had consulted during the first 3 hours. The
      average success rate of thrombolysis was 59% and reached 83% the first hour, 66%
      the second hour and 58.7% the third hour. In multivariate analysis, the three
      independent predictors factors of a fibrinolysis success were: active smoking,
      current treatment with beta blockers and the delay from onset chest pain to the
      ED visit less than 180 min. Conversely, diabetes was associated with fibrinolysis
      failure. Fibrinolysis got complicated by two intracerebral hemorrhages. Three
      patients had died in the ED. CONCLUSION: Two thirds of patients with STEMI have
      consulted 3 h after onset of chest pain. Fibrinolysis with streptokinase was
      effective in 59% of cases.

PMID- 24938238
TI  - [Somatic manifestations among depressed children: the case of complains and
      conversion symptoms].
AB  - BACKGROUND: If all authors agree on the presence of fundamental changes in mood,
      as the basis of the diagnosis of depression, little importance is accorded to
      other symptoms that can mislead the diagnosis: in particular, age and cultural
      influence on depressive symptoms. AIM: Our work aims to describe and assess the
      frequency of somatic complaints and symptoms of conversion in Tunisian children
      and adolescents followed for depressive disorders, and to compare, through a
      study of literature to populations from different cultures. METHODS: This work
      consisted in a retrospective review of children who consulted the Department of
      Child Psychiatry between 2008 and 2011 and in whom the diagnosis of depressive
      disorders was retained according to DSM IV criteria. Were searched all the
      conversion symptoms corresponding to the DSM IV diagnoses of conversion and
      dissociative disorders, as well as all the somatic complaints reported. Children
      with organic were excluded in order not to confuse the pain secondary to these
      disorders from those associated with depression. Also, children with mental
      retardation, moderate, severe or profound were not included because their
      difficulties of expression can alter the semiological assessment. RESULTS: 119
      children and adolescents aged 6 to19 years were included in the study. The mean
      age of the population was 11.6 years. Somatic complains were present in 37% of
      cases. Headaches were mostly represented (27.7%), followed by abdominal pain
      (14.3%). The presence of somatic complaints was significantly correlated with the
      presence of a comorbid anxiety (p=0.035). Conversion symptoms were present in
      22.7% of cases. They were significantly more frequent among girls (p=0.006) and
      in children whose father had a low level of education (p=0,013). Among the
      conversions, fainting were more common in girls (p=0.004), when the father's
      educational level was low (p=0.001), and when the geographical origin was rural
      (p=0.016). CONCLUSION: Conversion symptoms and somatic complaints are frequent in
      depressed children.

PMID- 24938239
TI  - Incidence and risk factors of postpartum anal incontinence: a prospective study
      of 503 cases.
AB  - BACKGROUND: Background: Anal incontinence is a devastating functional postpartum
      complication. it can cause deep deterioration in the quality of life. AIM: To
      assess the incidence of postpartum anal incontinence (PPAI) and the major risk
      factors predisposing for it in the short and middle terms. METHODS: This
      prospective observational study was conducted in the department of Obstetrics and
      Gynecology B in the Maternity and Neonatology Center of Tunis between March 1st
      and july 31st, 2009. RESULTS: Five hundred and three women were included. PPAI
      was 4.2% on the fourth day postpartum and 4% between weeks 6 and 8 postpartum.
      Predisposing factors to 4th day PPAI were forceps delivery (p<0.001), prolonged
      second stage of labor> 5hours (p=0.047), expulsion phase > 20mn (p<0.001),
      uterine revision (P=0.001) and first degree perineal lacerations (p<0.001).
      Between 6 and 8 weeks postpartum, identified risk factors were Shoulder dystocia
      (p<0.001), anu-vulvar distance < 2cm, perineal scars and transverse abdominal
      diameter >105mm (p<0.001). CONCLUSION: Preventive measures must be implemented in
      patients with PPAI risk factors.

PMID- 24938240
TI  - Ultrasound-guided spinal anesthesia in an obese patient.
AB  - We describe the case of 62-year-old man with a body mass index of 53,
      hypertension, diabetes mellitus and obstructive sleep apnea that was proposed for
      transurethral resection of prostate under spinal anesthesia. The surface landmark
      guided approach was difficult and was abandoned after many unsuccessful attempts.
      Spinal anesthesia was achieved in one attempt with ultrasound guidance using the
      midline approach at the identified level. The trajectory was determined from the
      transducer angle. 

PMID- 24938241
TI  - The pena-shoker syndrome type I: clinicopathological report of a recurrent case.

PMID- 24938242
TI  - Gallbladder agenesis intraoperatively diagnosed: a case report.

PMID- 24938243
TI  - An exceptional association: ulcerative colitis, amyloidosis and type-2 diabetes
      mellitus.

PMID- 24938244
TI  - [Prostate cancer with bilateral testicular metastasis].

PMID- 24938245
TI  - [Gastro-duodenal involvement in hernia of the linea alba revealed by digestive
      hemorrhage].

PMID- 24938246
TI  - Klippel Trenaunay syndrome in association with Sturge Weber syndrome about one
      case.

PMID- 24938247
TI  - [Unusual tumor of bile duct].

PMID- 24938248
TI  - A case of anti-Jo1 myositis associated with sarcoidosis.

PMID- 24938249
TI  - Vascular reconstruction following an oncologic resection of a sarcoma of the
      groin: about two cases.

PMID- 24938250
TI  - Tracheo-aortic fatal fistula after tracheostomy: a rare complication to keep in
      mind.

PMID- 24938251
TI  - Unusual feature of pycnodysostosis: pectus carinatum.

PMID- 24938252
TI  - [Systemic sarcoidosis revealed by an involvement of the nasal sinuses].

PMID- 24938274
TI  - Beneficial and harmful consequences of prepartum and postpartum antidepressant
      exposure.

PMID- 24938275
TI  - European Medicines Agency changes policy on clinical trial data publication.

PMID- 24938273
TI  - Relationship between Community Periodontal Index and Fecal Hemoglobin
      Concentration, an Indicator for Colorectal Neoplasm.
AB  - Periodontal disease and colorectal cancer have inflammatory processes in common.
      It is therefore worthwhile to investigate whether there is an association between
      periodontal probing depth and fecal hemoglobin concentration (FHbC), an indicator
      of colorectal neoplasms, in 40- to 44-year-old Taiwanese. We enrolled a total of
      6,214 attendees aged 40 to 44 yr who were participating in a community-based
      integrated screening program and who received both periodontal and FHbC
      examinations between 2003 and 2008. A proportional odds logistic regression model
      was used to estimate the odds ratios of different FHbC levels in treating an
      increased level of community periodontal index (CPI) measuring periodontal
      probing depth as ordinary data from 0 to 4. Periodontal probing depth with the
      order of CPI was in parallel with an increase in the mean values of FHbC: 21.3 +/
      156.3, 26.0 +/- 167.7, 27.2 +/- 151.1, and 39.5 +/- 255.7 ng/mL for CPI 0, CPI
      1, CPI 2, and CPI 3/4, respectively. The log-FHbC varied across the categories of
      CPI (p = .0078). After adjusting for age, sex, education level, smoking, alcohol
      intake, exercise, body mass index, and intake of meat and vegetables, subjects
      with positive fecal immunochemical test results (FHbC >= 100 ng/mL) had a 33%
      higher risk of deteriorating to severe CPI than did those within the normal range
      of fecal immunochemical test (FHbC < 100 ng/mL) (adjusted odds ratio = 1.33, 95%
      confidence interval: 1.03-1.73). A positive association was demonstrated between
      FHbC and periodontal probing depth assessed by CPI among 6,214 Taiwanese aged 40
      to 44 yr who participated in a community-based integrated health screening
      program. These results could have significant implications for early
      identification of high-risk individuals, as those with deep periodontal pockets
      should be advised to undergo screening for colorectal cancer at a younger age
      than commonly recommended. 

PMID- 24938276
TI  - Terrible triad of elbow.

PMID- 24938277
TI  - Long-term medication adherence in patients with ST-elevation myocardial
      infarction and primary percutaneous coronary intervention.
AB  - AIMS: Besides early percutaneous coronary intervention (PCI) long-term medical
      treatment is crucial for outcomes after ST-elevation myocardial infarction
      (STEMI). The present study aimed to identify predictors of adherence to evidence
      based medication in this high risk population. METHODS AND RESULTS: A total of
      1025 consecutive patients with adjudicated STEMI treated by primary PCI in a
      single centre as part of the Cologne Infarction Model (KIM) were prospectively
      analysed. Gender-specific multivariate predictors of long-term medication
      adherence were identified. Follow-up with available information on drug use was
      completed for 610 of 738 (82.7%) patients confirmed to be alive after a median
      period of 36 months. Adherence was persistently high for evidence-based
      medication with 90.8% for acetylsalicylic acid (ASA), 88.2% for statins, 87.5%
      for beta-blockers and 79.2% for ACE-inhibitors or angiotensin-receptor blockers
      (ARBs). Patients with a history of heart failure had a higher medication
      adherence to beta-blockers, ACE-inhibitors/ARBs and diuretics, whereas long-term
      prescription rates for calcium channel blockers (CCBs) were lower in patients
      with reduced versus preserved ejection fraction. Patients with a history of
      hypertension presented higher medication adherence to CCBs, ACE-inhibitors/ARBs
      and diuretics but not to beta-blockers. On multivariate analysis, age, body mass
      index (BMI), hypertension, chronic kidney disease and lack of PCI were
      independently associated with prescription of diuretics at follow-up. In women,
      adherence was lower to beta-blockers and higher to CCBs compared to men.
      CONCLUSION: In the high risk population of STEMI patients long-term adherence to
      evidence-based medication is high. The lower adherence to beta-blockers and
      higher prescription rate for CCBs in women needs particular attention.

PMID- 24938278
TI  - Informal allopathic provider knowledge and practice regarding control and
      prevention of TB in rural Bangladesh.
AB  - BACKGROUND: BRAC (formerly Bangladesh Rural Advancement Committee), in
      collaboration with the National Tuberculosis Control Programme, provides one full
      day training on TB to make informal allopathic providers knowledgeable for
      managing TB in rural Bangladesh. This study explored the knowledge and practices
      of the providers receiving the above training in the control and prevention of
      TB. METHODS: The study was conducted in 30 subdistricts, with 30 trained and 30
      untrained providers randomly selected from each subdistrict. Approximately 3%
      (49/1800) did not provide complete information. Pre-tested structured and semi
      structured questionnaires were used. RESULTS: TB was commonly perceived as a
      disease of only males (66.1%, 1157/1751). Only one-quarter knew about the
      bacterial cause of TB. Very few providers (2.1%, 36) had adequate knowledge
      regarding prevention of TB. They also lacked knowledge about TB treatment
      duration (71.6%, 1253), the meaning of DOTS (directly observed treatment, short
      course) (26.0%, 455) and multidrug resistance (20.6%, 360). Antibiotics (79.7%,
      1396) and cough syrup (75.0%, 1313) were commonly prescribed by providers despite
      symptoms suggestive of TB. However, 70.2% (613) and 74.5% (650) of trained
      providers' knowledge and practice scores were equal to or more than the mean
      scores (>=6.97 and >=6.6, respectively), whereas they were only 49.5% (435) and
      64.2% (563), respectively, among untrained providers (p<0.0001). CONCLUSIONS:
      Misperception, lack of knowledge and irrational use of antibiotics are challenges
      that need to be addressed for controlling and preventing TB efficiently.

PMID- 24938279
TI  - Age-specific exercise capacity threshold for mortality risk assessment in male
      veterans.
AB  - BACKGROUND: Mortality risk decreases beyond a certain fitness level. However,
      precise definition of this threshold is elusive and varies with age. Thus,
      fitness-related mortality risk assessment is difficult. METHODS AND RESULTS: We
      studied 18 102 male veterans (8305 blacks and 8746 whites). All completed an
      exercise test between 1986 and 2011 with no evidence of ischemia. We defined the
      peak metabolic equivalents (METs) level associated with no increase in all-cause
      mortality risk (hazard ratio, 1.0) for the age categories of <50, 50 to 59, 60 to
      69, and >=70 years. We used this as the threshold group to form additional age
      specific fitness categories based on METs achieved below and above it: least-fit
      (>2 METs below threshold; n=1692), low-fit (2 METs below threshold; n=4884),
      moderate-fit (2 METs above threshold; n=4646), fit (2.1-4 METs above threshold;
      n=1874), and high-fit (>4 METs above threshold; n=1301) categories. Multivariable
      Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals
      (CIs) for mortality across fitness categories. During follow-up (median=10.8
      years), 5102 individuals died. Mortality risk for the cohort and each age
      category increased for the least-fit and low-fit categories (HR, 1.51; 95% CI,
      1.37-1.66; and HR, 1.21; 95% CI, 1.12-1.30, respectively) and decreased for the
      moderate-fit; fit and high-fit categories (HR, 0.71; 95% CI, 0.65-0.78; HR, 0.63;
      95% CI, 0.56-0.78; and HR, 0.49; 95% CI, 0.41-0.58, respectively). The trends
      were similar for 5- and 10-year mortality risk. CONCLUSION: We defined age
      specific exercise capacity thresholds to guide assessment of mortality risk in
      individuals undergoing a clinical exercise test.

PMID- 24938280
TI  - The association between labour variables and primiparous women's experience of
      childbirth; a prospective cohort study.
AB  - BACKGROUND: Studies have suggested several risk factors for a negative birth
      experience among primiparas. Factors that are mentioned frequently include labour
      dystocia, operative intervention such as acute caesarean section or vacuum
      extraction, or the infant being transferred to neonatal care. Another important
      factor mentioned is lack of support from the midwife. METHODS: A study was made
      of the deliveries of 446 healthy primiparas in a prospective cohort study
      performed at Soder Hospital, Stockholm, Sweden. Samples of amniotic fluid were
      collected at delivery and the levels of amniotic fluid lactate (AFL) were
      measured to give an indication of the metabolism of the uterine tissue.
      Obstetrical data were collected from birth records.Postpartum, all the women
      included in the study were asked to complete the Wijma Delivery Experience
      Questionnaire (W-DEQ B) that measures the experience of a woman's delivery. The
      main objective of the project was to study well-known as well as new factors
      associated with negative experience of childbirth among a group of healthy
      primiparas. RESULTS: Risk factors for reporting a higher level of negative
      childbirth experience were shown to be a high level of AFL (AOR 3.1, 95%, CI; 1.1
      8.9), a longer latent phase (AOR 1.8, 95%, CI; 1.03-3.1), and a low Apgar score
      (<7 at 1 min) (AOR 13.3, 95%, CI; 1.6-111.0). Those women who had a negative
      birth experience wanted the midwife to be present more of the time during labour
      (p = 0.003). CONCLUSIONS: A high AFL level, as a marker of uterine metabolic
      status, and a longer latent phase are strongly associated with a negative
      experience of childbirth. A low 1 minute Apgar score of the newborn seems to have
      the strongest negative influence on the woman's experience of childbirth, even
      when the infant recovers immediately.

PMID- 24938281
TI  - Challenges to providing quality substance abuse treatment services for American
      Indian and Alaska Native communities: perspectives of staff from 18 treatment
      centers.
AB  - BACKGROUND: Substance abuse continues to exact a significant toll, despite
      promising advancements in treatment, and American Indian and Alaska Native
      (AI/AN) communities remain disproportionately impacted. Understanding the
      challenges to providing quality substance abuse treatment to AI/AN communities
      could ultimately result in more effective treatment interventions, but no multi
      site studies have examined this important issue. METHODS: This qualitative study
      examined the challenges of providing substance abuse treatment services for
      American Indian and Alaska Native (AI/AN) communities. We conducted key informant
      interviews and focus groups at 18 substance abuse treatment programs serving
      AI/AN communities. Seventy-six service participants (21 individuals in clinical
      administrative positions and 55 front-line clinicians) participated in the
      project. Interview transcripts were coded to identify key themes. RESULTS: We
      found that the challenges of bringing effective substance abuse treatment to
      AI/AN communities fell into three broad categories: challenges associated with
      providing clinical services, those associated with the infrastructure of
      treatment settings, and those associated with the greater service/treatment
      system. These sets of challenges interact to form a highly complex set of
      conditions for the delivery of these services. CONCLUSIONS: Our findings suggest
      that substance abuse treatment services for AI/AN communities require more
      integrated, individualized, comprehensive, and longer-term approaches to care.
      Our three categories of challenges provide a useful framework for eliciting
      challenges to providing quality substance abuse treatment in other substance
      abuse treatment settings.

PMID- 24938282
TI  - IL32 is progressively expressed in mycosis fungoides independent of helper T-cell
      2 and helper T-cell 9 polarization.
AB  - Mycosis fungoides, the most common type of cutaneous T-cell lymphoma (CTCL), is
      characterized by a helper T-cell 2 (Th2) skewing with a mature CD4(+) memory T
      cell phenotype. Using skin samples from patients with mycosis fungoides (n = 21),
      healthy volunteers (n = 17), and individuals with atopic dermatitis (n = 17) and
      psoriasis (n = 9), we found IL32 mRNA expression significantly higher in mycosis
      fungoides samples than in samples from benign inflammatory skin diseases, and its
      expression increases with disease progression. By IHC and immunofluorescence, we
      confirmed IL32 protein expression in many CD3(+)CD4(+) T cells and some
      epidermotropic T cells in mycosis fungoides lesions. MyLa cells (a mycosis
      fungoides cell line) express IL32, which, in turn, could promote cellular
      proliferation and viability in a dose-dependent fashion. IL32-treated MyLa and
      CTCL HH cells upregulated cell proliferation and survival genes. Of the major
      "polarizing" T-cell cytokines, only IFNgamma mRNA increases with mycosis
      fungoides progression and positively correlates with IL32 mRNA expression. Th2
      cytokines do not positively correlate with IL32 mRNA expression or mycosis
      fungoides progression. Furthermore, by flow cytometry, IL32 production by
      circulating activated T cells in healthy individuals was found in both
      IFNgamma(+) and IFNgamma(-) cells but not in IL4(+) or IL13(+) cells. In
      conclusion, we have identified IL32(+) cells as the likely tumor cells in mycosis
      fungoides, and demonstrated that IL32 mRNA expression increases with mycosis
      fungoides progression and is significantly higher than mRNA expression in other
      skin diseases, and that some IL32(+) T cells are independent from the defined Th
      subsets. Thus, IL32 may play a unique role in mycosis fungoides progression as an
      autocrine cytokine.

PMID- 24938284
TI  - Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of
      rheumatoid arthritis.

PMID- 24938283
TI  - Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer
      conjugates enhances the therapeutic index of tumor immunotherapy.
AB  - Despite the recent successes of using immune modulatory Abs in patients with
      cancer, autoimmune pathologies resulting from the activation of self-reactive T
      cells preclude the dose escalations necessary to fully exploit their therapeutic
      potential. To reduce the observed and expected toxicities associated with immune
      modulation, here we describe a clinically feasible and broadly applicable
      approach to limit immune costimulation to the disseminated tumor lesions of the
      patient, whereby an agonistic 4-1BB oligonucleotide aptamer is targeted to the
      tumor stroma by conjugation to an aptamer that binds to a broadly expressed
      stromal product, VEGF. This approach was predicated on the premise that by
      targeting the costimulatory ligands to products secreted into the tumor stroma,
      the T cells will be costimulated before their engagement of the MHC-peptide
      complex on the tumor cell, thereby obviating the need to target the costimulatory
      ligands to noninternalizing cell surface products expressed on the tumor cells.
      Underscoring the potency of stroma-targeted costimulation and the broad spectrum
      of tumors secreting VEGF, in preclinical murine tumor models, systemic
      administration of the VEGF-targeted 4-1BB aptamer conjugates engendered potent
      antitumor immunity against multiple unrelated tumors in subcutaneous,
      postsurgical lung metastasis, methylcholantrene-induced fibrosarcoma, and
      oncogene-induced autochthonous glioma models, and exhibited a superior
      therapeutic index compared with nontargeted administration of an agonistic 4-1BB
      Ab or 4-1BB aptamer.

PMID- 24938285
TI  - Epidemiology of primary Sjogren's syndrome: a systematic review and meta
      analysis.
AB  - OBJECTIVE: Epidemiological studies of primary Sjogren's syndrome (pSS) are
      crucial for describing the burden to society and the public medical system and
      for shedding light on aetiology. Previous reports of the epidemiology of pSS show
      variable outcomes. We conducted a systematic review of the epidemiology of pSS to
      assess the prevalence rates (PRs) and incidence rates (IRs), and to investigate
      possible geographic variations in pSS. METHODS: A systematic literature search of
      PubMed and Embase (updated to 22 October 2013) was performed to identify all
      published reports on the epidemiology of pSS. The incidence and prevalence rates
      of pSS were summarised with IRs or PRs and 95% CIs. RESULTS: The literature
      search yielded 1880 related citations. Only 21 fulfilled the inclusion criteria.
      According to a random-effects model, the pooled IR for pSS was 6.92 (95% CI 4.98
      to 8.86) per 100 000 person-years. The overall PR was 60.82 (95% CI 43.69 to
      77.94) cases per 100 000 inhabitants with a slightly lower estimate of Baodong
      Qin is BDQ, Jiaqi Wang is JQW, Zaixing Yang is ZXY, Renqian Zhong is RQZ. 43.03
      (25.74 to 60.31) cases per 100 000 inhabitants when only considering population
      based studies. The female/male ratio in incidence data was 9.15 (95% CI 3.35 to
      13.18). The female/male ratio in prevalence data was 10.72 (95% CI 7.35 to
      15.62). The overall age of pSS patients was 56.16 years (95% CI 52.54 to 59.78).
      CONCLUSIONS: Incidence and prevalence rates of pSS vary widely around the world.
      The results help us better understand the global epidemiology of pSS. Large
      population-based studies combining meticulous case-finding and case-ascertainment
      strategies are needed.

PMID- 24938286
TI  - Lysine propionylation is a prevalent post-translational modification in Thermus
      thermophilus.
AB  - Recent studies of protein post-translational modifications revealed that various
      types of lysine acylation occur in eukaryotic and bacterial proteins. Lysine
      propionylation, a newly discovered type of acylation, occurs in several proteins,
      including some histones. In this study, we identified 361 propionylation sites in
      183 mid-exponential phase and late stationary phase proteins from Thermus
      thermophilus HB8, an extremely thermophilic eubacterium. Functional
      classification of the propionylproteins revealed that the number of
      propionylation sites in metabolic enzymes increased in late stationary phase,
      irrespective of protein abundance. The propionylation sites on proteins expressed
      in mid-exponential and late stationary phases partially overlapped. Furthermore,
      amino acid frequencies in the vicinity of propionylation sites differed, not only
      between the two growth phases but also relative to acetylation sites. In
      addition, 33.8% of mid-exponential phase-specific and 80.0% of late stationary
      phase-specific propionylations (n >= 2) implied that specific mechanisms regulate
      propionylation in the cell. Moreover, the limited degree of overlap between
      lysine propionylation (36.8%) and acetylation (49.2%) sites in 67 proteins that
      were both acetylated and propionylated strongly suggested that the two acylation
      reactions are regulated separately by specific enzymes and may serve different
      functions. Finally, we also found that eight propionylation sites overlapped with
      acetylation sites critical for protein functions such as Schiff-base formation
      and ligand binding. 

PMID- 24938288
TI  - Tomato Pistil Factor STIG1 Promotes in Vivo Pollen Tube Growth by Binding to
      Phosphatidylinositol 3-Phosphate and the Extracellular Domain of the Pollen
      Receptor Kinase LePRK2.
AB  - The speed of pollen tube growth is a major determinant of reproductive success in
      flowering plants. Tomato (Solanum lycopersicum) STIGMA-SPECIFIC PROTEIN1 (STIG1),
      a small Cys-rich protein from the pistil, was previously identified as a binding
      partner of the pollen receptor kinase LePRK2 and shown to promote pollen tube
      growth in vitro. However, the in vivo function of STIG1 and the underlying
      mechanism of its promotive effect were unknown. Here, we show that a 7-kD
      processed peptide of STIG1 is abundant in the stigmatic exudate and accumulates
      at the pollen tube surface, where it can bind LePRK2. Antisense LePRK2 pollen was
      less responsive than wild-type pollen to exogenous STIG1 in an in vitro pollen
      germination assay. Silencing of STIG1 reduced both the in vivo pollen tube
      elongation rate and seed production. Using partial deletion and point mutation
      analyses, two regions underlying the promotive activity of the STIG1 processed
      peptide were identified: amino acids 80 to 83, which interact with LePRK2; and
      amino acids 88 to 115, which bind specifically to phosphatidylinositol 3
      phosphate [PI(3)P]. Furthermore, exogenous STIG1 elevated the overall redox
      potential of pollen tubes in both PI(3)P-dependent and LePRK2-dependent manners.
      Our results demonstrate that STIG1 conveys growth-promoting signals acting
      through the pollen receptor kinase LePRK2, a process that relies on the external
      phosphoinositide PI(3)P.

PMID- 24938287
TI  - NeuCode labels for relative protein quantification.
AB  - We describe a synthesis strategy for the preparation of lysine isotopologues that
      differ in mass by as little as 6 mDa. We demonstrate that incorporation of these
      molecules into the proteomes of actively growing cells does not affect cellular
      proliferation, and we discuss how to use the embedded mass signatures (neutron
      encoding (NeuCode)) for multiplexed proteome quantification by means of high
      resolution mass spectrometry. NeuCode SILAC amalgamates the quantitative accuracy
      of SILAC with the multiplexing of isobaric tags and, in doing so, offers up new
      opportunities for biological investigation. We applied NeuCode SILAC to examine
      the relationship between transcript and protein levels in yeast cells responding
      to environmental stress. Finally, we monitored the time-resolved responses of
      five signaling mutants in a single 18-plex experiment. 

PMID- 24938289
TI  - A Single-Pore Residue Renders the Arabidopsis Root Anion Channel SLAH2 Highly
      Nitrate Selective.
AB  - In contrast to animal cells, plants use nitrate as a major source of nitrogen.
      Following the uptake of nitrate, this major macronutrient is fed into the
      vasculature for long-distance transport. The Arabidopsis thaliana shoot expresses
      the anion channel SLOW ANION CHANNEL1 (SLAC1) and its homolog SLAC1 HOMOLOGOUS3
      (SLAH3), which prefer nitrate as substrate but cannot exclude chloride ions. By
      contrast, we identified SLAH2 as a nitrate-specific channel that is impermeable
      for chloride. To understand the molecular basis for nitrate selection in the
      SLAH2 channel, SLAC1 and SLAH2 were modeled to the structure of HiTehA, a
      distantly related bacterial member. Structure-guided site-directed mutations
      converted SLAC1 into a SLAH2-like nitrate-specific anion channel and vice versa.
      Our findings indicate that two pore-occluding phenylalanines constrict the pore.
      The selectivity filter of SLAC/SLAH anion channels is determined by the polarity
      of pore-lining residues located on alpha helix 3. Changing the polar character of
      a single amino acid side chain (Ser-228) to a nonpolar residue turned the nitrate
      selective SLAH2 into a chloride/nitrate-permeable anion channel. Thus, the
      molecular basis of the anion specificity of SLAC/SLAH anion channels seems to be
      determined by the presence and constellation of polar side chains that act in
      concert with the two pore-occluding phenylalanines.

PMID- 24938290
TI  - Linking genetics to structural biology: complex heterozygosity screening with
      actin alanine scan alleles identifies functionally related surfaces on yeast
      actin.
AB  - Previous genome-level genetic interaction screens with the single essential actin
      gene of yeast identified 238 nonessential genes that upon deletion result in
      deleterious, digenic complex haploinsufficiences with an actin null allele.
      Deletion alleles of these 238 genes were tested for complex heterozygous
      interactions with 32 actin alanine scan alleles, which target clusters of
      residues on the surface of actin. A total of 891 deleterious digenic combinations
      were identified with 203 of the 238 genes. Two-dimensional hierarchical cluster
      analysis of the interactions identified nine distinct groups, and the alleles
      within clusters tended to affect localized regions on the surface of actin. The
      mutants in one cluster all affect electrostatic interactions between stacked
      subunits in the long pitch helix of the actin filament. A second cluster that
      contains the most highly interactive alleles may disrupt the tropomyosin/myosin
      system, as one of the mutants in that cluster cannot support Type V myosin
      dependent movement of secretory vesicles in haploids and causes processivity
      defects in heterozygous diploids. These examples suggest the clusters represent
      mutations with shared protein-protein interaction defects. These results show
      that complex heterozygous interaction screens have benefit for detecting actin
      related genes and suggest that having actin filaments of mixed composition,
      containing both mutant and wild-type subunits, presents unique challenges to the
      cell. 

PMID- 24938292
TI  - Feasibility of using the Multinational Association of Supportive Care in Cancer
      Antiemesis Tool for assessment of chemotherapy-induced nausea and vomiting at the
      Tom Baker Cancer Centre.
AB  - INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) has been shown to
      adversely impact patient anxiety, quality of life, treatment adherence, and use
      of health care resources. CINV control still remains a challenge, and lack of
      effective communication between the patient and clinician has been highlighted in
      the literature as the main barrier to optimal control. The Multinational
      Association of Supportive Care in Cancer (MASCC) has developed a tool (MASCC
      Antiemesis Tool (MAT)) to improve assessment and subsequent management of CINV by
      enhancing communication between patients and their clinicians. This study
      assessed the feasibility of using the MAT in patients at the Tom Baker Cancer
      Centre. The secondary objective was to describe the incidence of CINV as
      identified by the tool. METHODS AND MATERIALS: This study involved a prospective
      survey using the MAT in patients receiving intravenous chemotherapy. Subjects
      completed the MAT twice post-chemotherapy regarding CINV symptoms and returned it
      at their next clinic appointment. Participants were also surveyed to evaluate
      feasibility with regard to using the MAT. RESULTS: Of the 50 patients recruited,
      56% returned surveys. The majority of patients reported that the MAT facilitated
      communication with their clinician, particularly those who had experienced CINV.
      Fifty-four percent of patients who returned the MAT reported CINV; however, less
      than half of them had received American Society of Clinical Oncology-recommended
      antiemetic regimens. Only four patients with CINV had antiemetic changes made for
      subsequent cycles. CONCLUSION: The MAT is a feasible tool which can improve
      communication of CINV symptoms between patients and clinicians, a foundational
      step toward improving CINV management.

PMID- 24938291
TI  - Harnessing natural sequence variation to dissect posttranscriptional regulatory
      networks in yeast.
AB  - Understanding how genomic variation influences phenotypic variation through the
      molecular networks of the cell is one of the central challenges of biology.
      Transcriptional regulation has received much attention, but equally important is
      the posttranscriptional regulation of mRNA stability. Here we applied a systems
      genetics approach to dissect posttranscriptional regulatory networks in the
      budding yeast Saccharomyces cerevisiae. Quantitative sequence-to-affinity models
      were built from high-throughput in vivo RNA binding protein (RBP) binding data
      for 15 yeast RBPs. Integration of these models with genome-wide mRNA expression
      data allowed us to estimate protein-level RBP regulatory activity for individual
      segregants from a genetic cross between two yeast strains. Treating these
      activities as a quantitative trait, we mapped trans-acting loci (activity
      quantitative trait loci, or aQTLs) that act via posttranscriptional regulation of
      transcript stability. We predicted and experimentally confirmed that a coding
      polymorphism at the IRA2 locus modulates Puf4p activity. Our results also
      indicate that Puf3p activity is modulated by distinct loci, depending on whether
      it acts via the 5' or the 3' untranslated region of its target mRNAs. Together,
      our results validate a general strategy for dissecting the connectivity between
      posttranscriptional [corrected] regulators and their upstream signaling pathways.

PMID- 24938293
TI  - Dosing algorithm for concomitant administration of sirolimus, tacrolimus, and an
      azole after allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplant patients are at risk of
      invasive fungal infections and prophylaxis with azole agents is common practice.
      The concomitant use of these agents with sirolimus and tacrolimus for the
      prevention of graft-versus-host disease may result in excessive immunosuppression
      or toxicity. METHODS: This retrospective study identified hospitalized patients
      who underwent allogeneic hematopoietic stem cell transplantation between August
      2009 and April 2011 at Rush University Medical Center. From this group, patients
      who underwent concomitant tacrolimus, sirolimus, and azole therapy were included
      for evaluation. The immunosuppression dosing in conjunction with azole use at
      discharge was analyzed to develop a dosing algorithm dependent on whether
      fluconazole, posaconazole, or voriconazole was used. RESULTS: A total of 36
      patients were screened for inclusion, of which 8 were excluded due to acute renal
      failure and/or hemolysis. The remaining patients were stratified by the azole
      they were concomitantly taking with tacrolimus and sirolimus. The fluconazole arm
      required the lowest magnitude of dose reductions, while voriconazole required the
      greatest. CONCLUSION: Dose reductions of 50-75% for both sirolimus and
      tacrolimus, in combination with standard dosing of azole antifungal agents, were
      necessary to achieve therapeutic drug concentrations for immunosuppressants and
      potentially avoid toxicities.

PMID- 24938294
TI  - KVFinder: steered identification of protein cavities as a PyMOL plugin.
AB  - BACKGROUND: The characterization of protein binding sites is a major challenge in
      computational biology. Proteins interact with a wide variety of molecules and
      understanding of such complex interactions is essential to gain deeper knowledge
      of protein function. Shape complementarity is known to be important in
      determining protein-ligand interactions. Furthermore, these protein structural
      features have been shown to be useful in assisting medicinal chemists during lead
      discovery and optimization. RESULTS: We developed KVFinder, a highly versatile
      and easy-to-use tool for cavity prospection and spatial characterization.
      KVFinder is a geometry-based method that has an innovative customization of the
      search space. This feature provides the possibility of cavity segmentation, which
      alongside with the large set of customizable parameters, allows detailed cavity
      analyses. Although the main focus of KVFinder is the steered prospection of
      cavities, we tested it against a benchmark dataset of 198 known drug targets in
      order to validate our software and compare it with some of the largely accepted
      methods. Using the one click mode, we performed better than most of the other
      methods, staying behind only of hybrid prospection methods. When using just one
      of KVFinder's customizable features, we were able to outperform all other
      compared methods. KVFinder is also user friendly, as it is available as a PyMOL
      plugin, or command-line version. CONCLUSION: KVFinder presents novel usability
      features, granting full customizable and highly detailed cavity prospection on
      proteins, alongside with a friendly graphical interface. KVFinder is freely
      available on http://lnbio.cnpem.br/bioinformatics/main/software/.

PMID- 24938295
TI  - How "moral" are the principles of biomedical ethics?--a cross-domain evaluation
      of the common morality hypothesis.
AB  - BACKGROUND: The principles of biomedical ethics - autonomy, non-maleficence,
      beneficence, and justice - are of paradigmatic importance for framing ethical
      problems in medicine and for teaching ethics to medical students and
      professionals. In order to underline this significance, Tom L. Beauchamp and
      James F. Childress base the principles in the common morality, i.e. they claim
      that the principles represent basic moral values shared by all persons committed
      to morality and are thus grounded in human moral psychology. We empirically
      investigated the relationship of the principles to other moral and non-moral
      values that provide orientations in medicine. By way of comparison, we performed
      a similar analysis for the business & finance domain. METHODS: We evaluated the
      perceived degree of "morality" of 14 values relevant to medicine (n1 = 317,
      students and professionals) and 14 values relevant to business & finance (n2 =
      247, students and professionals). Ratings were made along four dimensions
      intended to characterize different aspects of morality. RESULTS: We found that
      compared to other values, the principles-related values received lower ratings
      across several dimensions that characterize morality. By interpreting our finding
      using a clustering and a network analysis approach, we suggest that the
      principles can be understood as "bridge values" that are connected both to moral
      and non-moral aspects of ethical dilemmas in medicine. We also found that the
      social domain (medicine vs. business & finance) influences the degree of
      perceived morality of values. CONCLUSIONS: Our results are in conflict with the
      common morality hypothesis of Beauchamp and Childress, which would imply domain
      independent high morality ratings of the principles. Our findings support the
      suggestions by other scholars that the principles of biomedical ethics serve
      primarily as instruments in deliberated justifications, but lack grounding in a
      universal "common morality". We propose that the specific manner in which the
      principles are taught and discussed in medicine - namely by referring to
      conflicts requiring a balancing of principles - may partly explain why the degree
      of perceived "morality" of the principles is lower compared to other moral
      values.

PMID- 24938297
TI  - Gaseous fuels production from dried sewage sludge via air gasification.
AB  - Gasification is a perspective alternative method of dried sewage sludge thermal
      treatment. For the purpose of experimental investigations, a laboratory fixed-bed
      gasifier installation was designed and built. Two sewage sludge (SS) feedstocks,
      taken from two typical Polish wastewater treatment systems, were analysed: SS1,
      from a mechanical-biological wastewater treatment system with anaerobic
      stabilization (fermentation) and high temperature drying; and (SS2) from a
      mechanical-biological-chemical wastewater treatment system with fermentation and
      low temperature drying. The gasification results show that greater oxygen content
      in sewage sludge has a strong influence on the properties of the produced gas.
      Increasing the air flow caused a decrease in the heating value of the produced
      gas. Higher hydrogen content in the sewage sludge (from SS1) affected the
      produced gas composition, which was characterized by high concentrations of
      combustible components. In the case of the SS1 gasification, ash, charcoal, and
      tar were produced as byproducts. In the case of SS2 gasification, only ash and
      tar were produced. SS1 and solid byproducts from its gasification (ash and
      charcoal) were characterized by lower toxicity in comparison to SS2. However, in
      all analysed cases, tar samples were toxic. 

PMID- 24938296
TI  - Progress and challenges to the global waste management system.
AB  - Rapid economic growth, urbanization and increasing population have caused
      (materially intensive) resource consumption to increase, and consequently the
      release of large amounts of waste to the environment. From a global perspective,
      current waste and resource management lacks a holistic approach covering the
      whole chain of product design, raw material extraction, production, consumption,
      recycling and waste management. In this article, progress and different
      sustainability challenges facing the global waste management system are presented
      and discussed. The study leads to the conclusion that the current, rather
      isolated efforts, in different systems for waste management, waste reduction and
      resource management are indeed not sufficient in a long term sustainability
      perspective. In the future, to manage resources and wastes sustainably, waste
      management requires a more systems-oriented approach that addresses the root
      causes for the problems. A specific issue to address is the development of
      improved feedback information (statistics) on how waste generation is linked to
      consumption. 

PMID- 24938298
TI  - Impact of feedstock properties and operating conditions on sewage sludge
      gasification in a fixed bed gasifier.
AB  - This work presents results of experimental studies on the gasification process of
      granulated sewage sludge in a laboratory fixed bed gasifier. Nowadays, there is a
      large and pressing need for the development of thermal methods for sewage sludge
      disposal. Gasification is an example of thermal method that has several
      advantages over the traditional combustion. Gasification leads to a combustible
      gas, which can be used for the generation of useful forms of final energy. It can
      also be used in processes, such as the drying of sewage sludge directly in waste
      treatment plant. In the present work, the operating parameters were varied over a
      wide range. Parameters, such as air ratio lambda = 0.12 to 0.27 and the
      temperature of air preheating t = 50  degrees C to 250  degrees C, were found to
      influence temperature distribution and syngas properties. The results indicate
      that the syngas heating value decreases with rising air ratio for all analysed
      cases: i.e. for both cold and preheated air. The increase in the concentration of
      the main combustible components was accompanied by a decrease in the
      concentration of carbon dioxide. Preheating of the gasification agent supports
      the endothermic gasification and increases hydrogen and carbon monoxide
      production. 

PMID- 24938299
TI  - Impedance Analysis Using High-resolution Impedance Manometry Facilitates
      Assessment of Pharyngeal Residue in Patients With Oropharyngeal Dysphagia.
AB  - BACKGROUND/AIMS: Impedance analysis using high-resolution impedance manometry
      (HRIM) enables the recognition of pharyngeal residue in patients with
      oropharyngeal dysphagia. The aims of this study were to evaluate appropriate
      criteria for impedance analysis in a large patient cohort, as well as the
      diagnostic accuracy and agreement of analysis performed by HRIM trainees.
      METHODS: We reviewed 33 controls (13 males; median age, 61.2 years) and 104
      oropharyngeal dysphagia patients (61 males; median age, 70.4 years) who underwent
      a flexible endoscopic evaluation of swallowing study (FEES) and HRIM. Two experts
      compared the pharyngeal residue on FEES and impedance color pattern at 1,000,
      1,500 and 2,000 Omega of the impedance bar. Three trainees were given a 60
      minutes tutorial to determine the diagnostic accuracy and agreement of this
      analysis. RESULTS: The diagnostic sensitivity of experts for predicting liquid
      residue was 73.1% for 1,000 Omega, 96.2% for 1,500 Omega and 100% for 2,000
      Omega. Significantly higher sensitivity was observed at 1,500 Omega compared to
      1,000 Omega (P < 0.001). The diagnostic specificity of experts for liquid residue
      was 98.3% for 1,000 Omega, 96.6% for 1,500 Omega and 83.1% for 2,000 Omega. There
      was a higher specificity at 1,500 Omega compared to 2,000 Omega (P = 0.008). The
      kappa value among the 3 trainees was 0.89 and the diagnostic accuracy of the
      trainees for liquid residue was comparable to that of the experts. CONCLUSIONS:
      The impedance analysis at 1,500 Omega provides more accurate information for the
      detection of liquid residue, irrespective of the level of expertise.

PMID- 24938300
TI  - A systems biology approach to understand the pathophysiological mechanisms of
      cardiac pathological hypertrophy associated with rosiglitazone.
AB  - BACKGROUND: Cardiac pathological hypertrophy is associated with a significantly
      increased risk of coronary heart disease and has been observed in diabetic
      patients treated with rosiglitazone whereas most published studies do not suggest
      a similar increase in risk of cardiovascular events in pioglitazone-treated
      diabetic subjects. This study sought to understand the pathophysiological and
      molecular mechanisms underlying the disparate cardiovascular effects of
      rosiglitazone and pioglitazone and yield knowledge as to the causative nature of
      rosiglitazone-associated cardiac hypertrophy. METHODS: We used a high-fat diet
      induced pre-diabetic mouse model to allow bioinformatics analysis of the
      transcriptome of the heart of mice treated with rosiglitazone or pioglitazone.
      RESULTS: Our data show that rosiglitazone and pioglitazone both markedly improved
      systemic markers for glucose homeostasis, fasting plasma glucose and insulin, and
      the urinary excretion of albumin. Only rosiglitazone, but not pioglitazone,
      tended to increase atherosclerosis and induced pathological cardiac hypertrophy,
      based on a significant increase in heart weight and increased expression of the
      validated markers, ANP and BNP. Functional enrichment analysis of the
      rosiglitazone-specific cardiac gene expression suggests that a shift in cardiac
      energy metabolism, in particular decreased fatty acid oxidation toward increased
      glucose utilization as indicated by down regulation of relevant PPARalpha and
      PGC1alpha target genes. This underlies the rosiglitazone-associated pathological
      hypertrophic cardiac phenotype in the current study. CONCLUSION: Application of a
      systems biology approach uncovered a shift in energy metabolism by rosiglitazone
      that may impact cardiac pathological hypertrophy.

PMID- 24938301
TI  - Elastic compression stockings fail to prevent post-thrombotic syndrome after a
      first deep vein thrombosis.

PMID- 24938304
TI  - Bilateral adrenal incidentaloma with subclinical hypercortisolemia: indications
      for surgery.
AB  - INTRODUCTION: According to some authors, a higher incidence of subclinical
      hypercortisolemia is found among patients with bilateral benign adrenal tumors
      than in those with unilateral tumors. It is still unknown whether all patients
      with bilateral adrenal tumors and subclinical hypercortisolemia should undergo
      surgery, and, if so, which tumor should be removed first. OBJECTIVES: The aim of
      the study was to investigate whether unilateral adrenalectomy can lead to
      resolution of hypercortisolemia in patients with bilateral adrenal tumors and to
      improvement of their clinical status. PATIENTS AND METHODS: The study group
      consisted of 25 patients with bilateral benign adrenal tumors and subclinical
      hypercortisolemia. In 24 patients, unilateral adrenalectomy was performed. The
      adrenal gland was selected for removal on the basis of scintigraphy and/or tumor
      diameter. Cortisol concentrations were measured before the surgery and at 1 and 6
      months after the surgery at 8:00 AM, 10:00 PM, and after dexamethasone
      suppression. The morning blood levels of adrenocorticotropic hormone,
      dehydroepiandrosterone, 17-hydroxyprogesterone, glycated hemoglobin, and lipid
      profile were determined. RESULTS: In all surgical patients, hypercortisolemia
      resolved after the surgery. However, only in 14 patients (58%), the clinical
      improvement was evident (improved control of diabetes and hypertension, body mass
      loss). CONCLUSIONS: Although subclinical hypercortisolemia resolved after surgery
      in all patients with bilateral adrenal tumors, only patients with poorly
      controlled diabetes and hypertension and a rapid increase in body mass benefited
      from the surgery.

PMID- 24938302
TI  - Vitamin D and mortality: meta-analysis of individual participant data from a
      large consortium of cohort studies from Europe and the United States.
AB  - OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D
      concentrations (25(OH)D) and mortality in a large consortium of cohort studies
      paying particular attention to potential age, sex, season, and country
      differences. DESIGN: Meta-analysis of individual participant data of eight
      prospective cohort studies from Europe and the US. SETTING: General population.
      PARTICIPANTS: 26,018 men and women aged 50-79 years. MAIN OUTCOME MEASURES: All
      cause, cardiovascular, and cancer mortality. RESULTS: 25(OH)D concentrations
      varied strongly by season (higher in summer), country (higher in US and northern
      Europe) and sex (higher in men), but no consistent trend with age was observed.
      During follow-up, 6695 study participants died, among whom 2624 died of
      cardiovascular diseases and 2227 died of cancer. For each cohort and analysis,
      25(OH)D quintiles were defined with cohort and subgroup specific cut-off values.
      Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57
      (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular
      mortality were similar in magnitude to that for all-cause mortality in subjects
      both with and without a history of cardiovascular disease at baseline. With
      respect to cancer mortality, an association was only observed among subjects with
      a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all
      quintiles suggest curvilinear, inverse, dose-response curves for the
      aforementioned relationships. No strong age, sex, season, or country specific
      differences were detected. Heterogeneity was low in most meta-analyses.
      CONCLUSIONS: Despite levels of 25(OH)D strongly varying with country, sex, and
      season, the association between 25(OH)D level and all-cause and cause-specific
      mortality was remarkably consistent. Results from a long term randomised
      controlled trial addressing longevity are being awaited before vitamin D
      supplementation can be recommended in most individuals with low 25(OH)D levels.

PMID- 24938305
TI  - Belowground advantages in construction cost facilitate a cryptic plant invasion.
AB  - The energetic cost of plant organ construction is a functional trait that is
      useful for understanding carbon investment during growth (e.g. the resource
      acquisition vs. tissue longevity tradeoff), as well as in response to global
      change factors like elevated CO2 and N. Despite the enormous importance of roots
      and rhizomes in acquiring soil resources and responding to global change,
      construction costs have been studied almost exclusively in leaves. We sought to
      determine how construction costs of aboveground and belowground organs differed
      between native and introduced lineages of a geographically widely dispersed
      wetland plant species (Phragmites australis) under varying levels of CO2 and N.
      We grew plants under ambient and elevated atmospheric CO2, as well as under two
      levels of soil nitrogen. We determined construction costs for leaves, stems,
      rhizomes and roots, as well as for whole plants. Across all treatment conditions,
      the introduced lineage of Phragmites had a 4.3 % lower mean rhizome construction
      cost than the native. Whole-plant construction costs were also smaller for the
      introduced lineage, with the largest difference in sample means (3.3 %) occurring
      under ambient conditions. In having lower rhizome and plant-scale construction
      costs, the introduced lineage can recoup its investment in tissue construction
      more quickly, enabling it to generate additional biomass with the same energetic
      investment. Our results suggest that introduced Phragmites has had an
      advantageous tissue investment strategy under historic CO2 and N levels, which
      has facilitated key rhizome processes, such as clonal spread. We recommend that
      construction costs for multiple organ types be included in future studies of
      plant carbon economy, especially those investigating global change. 

PMID- 24938303
TI  - Impact of patient navigation on timely cancer care: the Patient Navigation
      Research Program.
AB  - BACKGROUND: Patient navigation is a promising intervention to address cancer
      disparities but requires a multisite controlled trial to assess its
      effectiveness. METHODS: The Patient Navigation Research Program compared patient
      navigation with usual care on time to diagnosis or treatment for participants
      with breast, cervical, colorectal, or prostate screening abnormalities and/or
      cancers between 2007 and 2010. Patient navigators developed individualized
      strategies to address barriers to care, with the focus on preventing delays in
      care. To assess timeliness of diagnostic resolution, we conducted a meta-analysis
      of center- and cancer-specific adjusted hazard ratios (aHRs) comparing patient
      navigation vs usual care. To assess initiation of cancer therapy, we calculated a
      single aHR, pooling data across all centers and cancer types. We conducted a
      metaregression to evaluate variability across centers. All statistical tests were
      two-sided. RESULTS: The 10521 participants with abnormal screening tests and 2105
      with a cancer or precancer diagnosis were predominantly from racial/ethnic
      minority groups (73%) and publically insured (40%) or uninsured (31%). There was
      no benefit during the first 90 days of care, but a benefit of navigation was seen
      from 91 to 365 days for both diagnostic resolution (aHR = 1.51; 95% confidence
      interval [CI] = 1.23 to 1.84; P < .001)) and treatment initiation (aHR = 1.43;
      95% CI = 1.10 to 1.86; P < .007). Metaregression revealed that navigation had its
      greatest benefits within centers with the greatest delays in follow-up under
      usual care. CONCLUSIONS: Patient navigation demonstrated a moderate benefit in
      improving timely cancer care. These results support adoption of patient
      navigation in settings that serve populations at risk of being lost to follow-up.

PMID- 24938307
TI  - Adverse perinatal outcomes associated with moderate or severe maternal anaemia
      based on parity in Finland during 2006-10.
AB  - BACKGROUND: Anaemia during pregnancy is an important public health problem. We
      investigated whether the association between maternal anaemia during pregnancy
      and adverse perinatal outcomes differed between nulliparous and multiparous
      women. METHODS: A retrospective population-based cohort study was conducted using
      data on all singleton births (n = 290 662) recorded in the Finnish Medical Birth
      Register during 2006-10. Maternal anaemia was defined as a maternal haemoglobin
      level of <100 g/L). Adverse perinatal outcomes that were examined included
      preterm delivery (<37 weeks), small-for-gestational age (SGA, <2 standard
      deviation), admission to neonatal intensive care, stillbirth, early neonatal
      death, and major congenital anomalies. An association between anaemia and adverse
      outcomes was assessed by logistic regression analysis. RESULTS: The prevalence of
      anaemia during pregnancy was 2.5% among nulliparous women and 2.3% among
      multiparous women. Among nulliparous women, anaemia was not associated with
      adverse perinatal outcomes. Among multiparous women, anaemia was associated with
      preterm delivery (adjusted odds ratio [aOR] 1.32, [95% CI 1.14, 1.53]), SGA (aOR
      1.27, [95% CI 1.04, 1.55]), and admission to neonatal intensive care (aOR 1.23,
      [95% CI 1.10, 1.38]); there was a trend towards increased odds of major
      congenital anomalies (aOR 1.15, [95% CI 0.99, 1.34]). CONCLUSIONS: These data
      underscore that maternal anaemia is associated with several adverse perinatal
      outcomes. This association was, however, confined to multiparous women. Future
      research should explore in detail the timing of anaemia in these associations.

PMID- 24938306
TI  - Development of a survey instrument to investigate the primary care factors
      related to differences in cancer diagnosis between international jurisdictions.
AB  - BACKGROUND: Survival rates following a diagnosis of cancer vary between
      countries. The International Cancer Benchmarking Partnership (ICBP), a
      collaboration between six countries with primary care led health services, was
      set up in 2009 to investigate the causes of these differences. Module 3 of this
      collaboration hypothesised that an association exists between the readiness of
      primary care physicians (PCP) to investigate for cancer - the 'threshold' risk
      level at which they investigate or refer to a specialist for consideration of
      possible cancer - and survival for that cancer (lung, colorectal and ovarian). We
      describe the development of an international survey instrument to test this
      hypothesis. METHODS: The work was led by an academic steering group in England.
      They agreed that an online survey was the most pragmatic way of identifying
      differences between the jurisdictions. Research questions were identified through
      clinical experience and expert knowledge of the relevant literature.A survey
      comprising a set of direct questions and five clinical scenarios was developed to
      investigate the hypothesis. The survey content was discussed and refined
      concurrently and repeatedly with international partners. The survey was validated
      using an iterative process in England. Following validation the survey was
      adapted to be relevant to the health systems operating in other jurisdictions and
      translated into Danish, Norwegian and Swedish, and into Canadian and Australian
      English. RESULTS: This work has produced a survey with face, content and cross
      cultural validity that will be circulated in all six countries. It could also
      form a benchmark for similar surveys in countries with similar health care
      systems. CONCLUSIONS: The vignettes could also be used as educational resources.
      This study is likely to impact on healthcare policy and practice in participating
      countries.

PMID- 24938308
TI  - Global pathways to men's caregiving: mixed methods findings from the
      International Men and Gender Equality Survey and the Men Who Care study.
AB  - Promoting men's participation in unpaid care work is part of the Programme of
      Action for the International Conference on Population and Development. However,
      men's involvement in care work does not mirror the advances women have made in
      paid work outside the home. This mixed method study explores which men are more
      involved in caregiving, and what childhood and adulthood factors influence their
      level of involvement. Quantitative research presents findings from 1169 men
      across six countries with children aged 0-4, and a qualitative study presents
      findings from in-depth interviews with 83 men engaged in atypical caregiving
      practices. Survey research finds that being taught to care for children,
      witnessing one's father take care of one's siblings, respondents' present
      attitudes about gender equality and having outside help (or none, in some cases)
      were all also associated with men's higher level of involvement. Qualitative
      research reveals that men's experiences of violence, the normalisation of
      domestic work as children and life circumstances rather than greater-than-average
      beliefs in gender equality all propelled them into care work. Findings suggest
      that engaging more men into care work implies changes to policies and structural
      realities in the workplace coupled with changing gender attitudes. These insights
      inform policy and practice aimed at promoting greater involvement in care work by
      men. 

PMID- 24938309
TI  - Abnormal sensory perception or peristaltic dysfunction: which one is associated
      with symptoms?

PMID- 24938310
TI  - Novel common variants and susceptible haplotype for exfoliation glaucoma specific
      to Asian population.
AB  - The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with
      exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS).
      However, the risk allele of a variant in LOXL1 has been found to be inverted
      between Asian and Caucasian populations. Therefore, we newly performed a genome
      wide association study using 201 XFS/XFG and 697 controls in Japanese, and
      identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs)
      distributing in not only LOXL1 but also TBC1D21 and PML at the 15q24.1 locus.
      These SNPs were confirmed by an independent population consisted of 121 XFS/XFG
      and 263 controls in Japanese. Moreover, further analyses revealed a unique
      haplotype structure only from the combination of TBC1D21 and LOXL1 variants
      showing a high XFS/XFG susceptibility specific for the Asian population. Although
      there still should be other gene(s) in the other region(s) contributing to the
      disease process, these results suggested that the combination of newly discovered
      variants in these genes might be useful for precise XFG risk assessment, as well
      as for elucidating the molecular mechanism of XFG pathogenesis through XFS. 

PMID- 24938311
TI  - Pretreatment attrition and formal withdrawal during treatment and their
      predictors: an exploratory study of the anxiety online data.
AB  - BACKGROUND: Although in its infancy, the field of e-mental health interventions
      has been gaining popularity and afforded considerable research attention.
      However, there are many gaps in the research. One such gap is in the area of
      attrition predictors at various stages of assessment and treatment delivery.
      OBJECTIVE: This exploratory study applied univariate and multivariate analysis to
      a large dataset provided by the Anxiety Online (now called Mental Health Online)
      system to identify predictors of attrition in treatment commencers and in those
      who formally withdrew during treatment based on 24 pretreatment demographic and
      personal variables and one clinical measure. METHODS: Participants were assessed
      using a complex online algorithm that resulted in primary and secondary diagnoses
      in accordance with the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, Text Revision (DSM-IV-TR). Those who received a primary or
      secondary diagnosis of 1 of 5 anxiety disorders (generalized anxiety disorder,
      social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress
      disorder, and panic disorder) were offered an online 12-week disorder-specific
      treatment program. RESULTS: Of 9394 potential participants, a total of 3880
      clients enrolled and 5514 did not enroll in one of the treatment programs
      following the completion of pretreatment assessment measures (pretreatment
      attrition rate: 58.70%). A total of 3199 individuals did not formally withdraw
      from the 12-week treatment cycle, whereas 142 individuals formally dropped out
      (formal withdrawal during treatment dropout rate of 4.25%). The treatment
      commencers differed significantly (P<.001-.03) from the noncommencers on several
      variables (reason for registering, mental health concerns, postsecondary
      education, where first heard about Anxiety Online, Kessler-6 score, stage of
      change, quality of life, relationship status, preferred method of learning, and
      smoking status). Those who formally withdrew during treatment differed
      significantly (P=.002-.03) from those who did not formally withdraw in that they
      were less likely to express concerns about anxiety, stress, and depression; to
      rate their quality of life as very poor, poor, or good; to report adequate level
      of social support; and to report readiness to make or were in the process of
      making changes. CONCLUSIONS: This exploratory study identified predictors of
      pretreatment attrition and formal withdrawal during treatment dropouts for the
      Anxiety Online program. TRIAL REGISTRATION: Australian and New Zealand Clinical
      Trials Registry ACTRN121611000704998;
      http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at
      http://www.webcitation.org/618r3wvOG).

PMID- 24938312
TI  - Three-dimensional microstructure of high-performance pulsed-laser deposited Ni
      YSZ SOFC anodes.
AB  - The Ni-yttria-stabilized zirconia (YSZ) anode functional layer in solid oxide
      fuel cells produced by pulsed laser-deposition was studied using three
      dimensional tomography. Anode feature sizes of ~130 nm were quite small relative
      to typical anodes, but errors arising in imaging and segmentation were shown
      using a sensitivity analysis to be acceptable. Electrochemical characterization
      showed that these cells achieved a relatively high maximum power density of 1.4 W
      cm(-2) with low cell resistance at an operating temperature of 600  degrees C.
      The tomographic data showed anode three-phase boundary density of ~56 MUm(-2),
      more than 10 times the value observed in conventional Ni-YSZ anodes. Anode
      polarization resistance values, predicted by combining the structural data and
      literature values of three-phase boundary resistance in an electrochemical model,
      were consistent with measured electrochemical impedance spectra, explaining the
      excellent intermediate-temperature performance of these cells.

PMID- 24938313
TI  - Clinical trials involving cats: what factors affect owner participation?
AB  - STUDY RATIONALE: Clinical trials are frequently hindered by difficulties in
      recruiting eligible participants, increasing the timeline and limiting
      generalizability of results. In veterinary medicine, where proxy enrollment is
      required, no studies have detailed what factors influence owner participation in
      clinical trials involving cats. We aimed to investigate these factors through a
      survey of owners at first opinion practices. PROTOCOL: The survey was designed
      using feedback from a pilot study and input from clinical researchers. Owners
      were asked demographic questions and whether they would, would not, or were
      unsure about participating in a clinical trial with their cat. They then ranked
      the importance and influence of various factors on participation using a five
      point Likert-type scale, and incentives from most to least encouraging. A total
      of 413 surveys were distributed to cat owners at four hospitals, two feline-only
      and two multi-species; 88.6% were completed. Data for importance and influence
      factors as well as incentive rankings were analyzed overall, and by hospital
      type, location and whether owners would consider participating. FINDINGS: The
      most influential factors were trust in the organization, benefit to the cat and
      veterinarian recommendation. Importance and influence factors varied by
      willingness to participate. Ranked incentives were not significantly different
      across groups, with 'Free Services' ranked highest. RELEVANCE: This study
      provides a first look at what factors influence participation in clinical trials
      with cats. Given the importance placed in the recommendation of veterinarians,
      continued work is needed to determine veterinarian-related factors affecting
      clinical trial participation. The results provide guidance towards improved
      clinical trial design, promotion and education.

PMID- 24938314
TI  - Insulin detemir treatment in diabetic cats in a practice setting.
AB  - Insulin detemir is a long-acting insulin analogue and may represent a valuable
      treatment option for diabetic cats. So far, only one study addressing detemir
      treatment of diabetic cats has been published, and this was based on an intensive
      blood glucose monitoring protocol. The aim of the current, retrospective study
      was to evaluate the effect of detemir therapy in diabetic cats in a general
      clinical setting. Fourteen diabetic cats with a follow-up period of at least 3
      months were included. Data were collected from medical records at the University
      Hospital for Companion Animals, University of Copenhagen, Denmark. Thirteen of 14
      cats achieved moderate or excellent control of clinical symptoms within the
      initial 3 months of detemir therapy, including five cats previously treated
      unsuccessfully with other types of insulin. Clinical improvements were noted
      after 1 month of therapy and continued over time. Three cats achieved remission
      within the initial 3 months and none experienced a diabetic relapse during the
      study period. One cat achieved remission after 13 months of therapy. Improvements
      in clinical symptoms were markedly better than indicated by blood glucose and
      serum fructosamine concentrations. The safety of detemir was very high, with only
      two reported episodes of clinical hypoglycaemia, neither of which required
      veterinary attention. Based on these results detemir can be recommended for the
      treatment of diabetic cats, including cats previously treated unsuccessfully with
      other types of insulin. 

PMID- 24938316
TI  - Effect of boiling in water of barley and buckwheat groats on the antioxidant
      properties and dietary fiber composition.
AB  - In recent years, there has been an ever-increasing interest in the research of
      polyphenols obtained from dietary sources, and their antioxidative properties.
      The purpose of this study was to determine the effect of boiling buckwheat and
      barley groats on the antioxidant properties and dietary fiber composition.
      Antioxidative properties were investigated using methyl linoleate model system,
      by assessing the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity
      and metal chelating activity. The results were compared with butylated
      hydroxytoluene (BHT). Raw barley and buckwheat groats extracts showed higher DPPH
      scavenging ability compared to boiled barley and buckwheat groats extracts. Raw
      barley groats extract exhibited higher antioxidant activity than boiled groats
      extract in the methyl linoleate emulsion. Higher chelating ability in relation to
      Fe (II) ions was observed for boiled groats extracts as compared to raw groats
      extracts. BHT showed small antiradical activity and metal chelating activity,
      while showing higher antioxidative activity in emulsion system. The analysis of
      groats extracts using HPLC method showed the presence of rutin, catechin,
      quercetin, gallic, p-hydroxybenzoic, p-coumaric, o-coumaric, vanillic, sinapic,
      and ferulic acids. Differences in the content of dietary fiber and its fractions
      were observed in the examined products. The highest total dietary fiber content
      was detected in boiled buckwheat groats, while the lowest - in boiled barley
      groats. The scientific achievements of this research could help consumers to
      choose those cereal products available on the market, such as barley and
      buckwheat groats, which are a rich source of antioxidative compounds and dietary
      fiber. 

PMID- 24938317
TI  - Erratum to: Differential distribution of Y-box-binding protein 1 and cold shock
      domain protein A in developing and adult human brain.

PMID- 24938315
TI  - Podoplanin-positive cancer cells at the edge of esophageal squamous cell
      carcinomas are involved in invasion.
AB  - Podoplanin (PDPN) is a well established lymphatic endothelial marker and has
      frequently been observed in cancer cells at the edge of cancer masses. Previous
      studies investigating the association between PDPN expression and patient
      prognosis have had contradictory results. In the present study, it was
      hypothesized that the different locations of PDPN-positive cells may explain
      these varying results. The present study aimed to focus on PDPN expression at the
      edge of esophageal cancer cell nests. In order to analyze the clinical
      significance of this PDPN expression, immunohistochemistry was performed using
      esophageal cancer tissue microarrays. PDPN expression at the edge of the cancer
      cell nest was found to be significantly associated with invasion (P<0.05) and
      poor prognosis (P<0.001) in patients with cancer. To further investigate the role
      of PDPN expression in cancer cells, the PDPN gene was cloned and transfected into
      esophageal squamous cell carcinoma (ESCC) cell lines. PDPN expression was also
      knocked down using small interfering RNA. PDPN-positive cancer cells were found
      to exhibit invasion characteristics. Thus, PDPN expression at the edge of a
      cancer cell nest may indicate invasion and represent a poor prognostic factor for
      ESCCs.

PMID- 24938318
TI  - Gabapentin versus pregabalin in relieving early post-surgical neuropathic pain in
      patients after lumbar disc herniation surgery: a prospective clinical trial.
AB  - OBJECTIVES: The roles of gabapentin and pregabalin are well established in the
      management of chronic neuropathic pain. Here, we investigated the effectiveness
      of pregabalin and gabapentin for treating acute neuropathic pain following lumbar
      discectomy. METHODS: This prospective, non-randomized, and observational study
      included 54 patients who experienced acute neuropathic pain after lumbar
      discectomy. The assessments included the Leeds assessment of neuropathic symptoms
      and signs scale (LANSS), the Oswestry disability index (ODI), and the visual
      analog scale (VAS) pre-operatively and at 3 days, 6 months, and 1 year after
      surgery. The LANSS scores ?12 suggest the presence of neuropathic pain. Those
      patients who reported neuropathic pain were randomly treated with gabapentin or
      pregabalin. RESULTS: In the gabapentin group, the LANSS scores increased to 14 at
      3 days after surgery. The patients improved neurologically and on the LANSS,
      which decreased to 10 points 6 months after surgery and to 4 points at 1 year (P
      < 0.001). In the pregabalin group, the LANSS scores increased from 12 to 16
      points on post-operative day 3 and then decreased to 12 and 5 at the 6-month and
      1-year follow-ups, respectively (both P < 0.001). The ODI and VAS scores
      significantly improved in both groups (P < 0.001). DISCUSSION: Many patients may
      suffer from neuropathic pain in the early post-surgical period after lumbar
      discectomy. Gabapentin and pregabalin are anticonvulsant agents that may decrease
      perioperative central sensitization and early post-surgical neuropathic pain.
      Gabapentin and pregabalin effectively relieved neuropathic pain and prevented the
      conversion of acute pain to chronic pain at the 1-year follow-up after lumbar
      discectomy.

PMID- 24938319
TI  - Alterations in the gray matter volume in transient ischemic attack: a voxel-based
      morphometry study.
AB  - BACKGROUND: Several studies have emphasized that transient ischemic attack (TIA)
      patients suffered functional impairments, but whether underlying morphological
      alterations exist remains unclear. This study aims to detect possible gray matter
      volume (GMV) alterations in patients with TIA using voxel-based morphometry (VBM)
      method. METHODS: High-resolution T1-weighted anatomical images of 21 patients
      were compared with 21 healthy controls of matching age, gender, and education.
      Changes in the GMV were observed using VBM technique, followed by two-sample t
      test analysis to detect the differences in the GMV between TIA patients and
      healthy controls. Correlations between the clinical parameters and the Montreal
      cognitive assessment (MoCA) scores, and the altered GMV in TIAs, were
      investigated. RESULTS: Two-sample t-test analysis revealed a significant GMV
      reduction in specific regions in the default mode network (DMN) in TIA patients,
      including the bilateral medial frontal gyrus, anterior cingulate cortex (ACC),
      and precuneus. No correlation was found between the reduced GMV and MoCA scores
      and clinical parameters. CONCLUSION: Transient ischemic attack patients showed
      widespread morphology atrophy in DMN, suggesting that, despite the absence of a
      cerebral infarction, ischemic injury may induce structural abnormalities and
      eventually contribute to functional impairments in TIA patients. Our results may
      provide a valuable basis for the pathophysiological mechanism related to the
      cognitive dysfunction of TIA from the view of brain morphology.

PMID- 24938320
TI  - Early morphological recovery of the optic chiasm is associated with excellent
      visual outcome in patients with compressive chiasmal syndrome caused by pituitary
      tumors.
AB  - OBJECTIVES: The study objectives are (1) to identify factors predicting the
      excellent visual recovery after transsphenoidal removal of pituitary tumors and
      (2) to describe the association of excellent visual recovery and early
      restoration of symmetry of the decompressed optic chiasm. METHODS: Thirty-five
      patients with visual symptoms due to pituitary tumors underwent endoscopic
      endonasal surgery. All patients received perioperative diagnostic magnetic
      resonance (MR) imaging and ophthalmological assessments within 2 weeks before
      surgery, within 2 weeks after surgery, and 3 months or later after surgery.
      Preoperative best-corrected visual acuity (BCVA ? 20/20), degree of visual field
      deficit (VFD, less than half of VF), thickness of retinal nerve fiber layer
      (RNFL) measured by optical coherence tomography (OCT), and thickness of ganglion
      cell complex (GCC) measured by OCT were considered for statistical analysis as
      predictive factors of VF outcome. Multivariate logistic regression models were
      used in statistical evaluation of data. RESULTS: In the multivariate analysis,
      RNFL (odds ratio  =  62.137, P < 0.001) and preoperative VFD (odds ratio  = 
      8.244, P < 0.02) proved to be effective as factors predicting sufficient VF
      recovery. Postoperative restoration of symmetry of the optic chiasm was related
      to sufficient VF recovery (P < 0.0001, Fisher's exact test) and RNFL (P < 0.0001,
      Fisher's exact test). DISCUSSION: Early decompression is crucial for sufficient
      VF recovery, in particular, while RNFL preserves normal or borderline thickness
      and while VFD keeps within hemianopia. Morphological reversibility is associated
      with functional reversibility in the optic chiasm compressed by a pituitary
      tumor. In particular, early morphological recovery suggests functional recovery,
      which indicates neurocyte reserve in the compressed optic pathway with functional
      recovery.

PMID- 24938321
TI  - Valsartan prevents neointimal hyperplasia after carotid artery stenting by
      suppressing endothelial cell injuries.
AB  - OBJECTIVES: Restenosis or neointimal hyperplasia remains an important
      complication after carotid artery stenting (CAS) for carotid artery stenosis. The
      purpose of this study was to examine if an anti-hypertensive drug, angiotensin
      receptor blocker (ARB), prevents post-CAS neointimal hyperplasia during the first
      1-year period after CAS, and to clarify the possible mechanisms. METHODS:
      Hypertension had been treated with a calcium channel blocker (CCB) and/or an ARB,
      valsartan, by the preference of the neurosurgeon in charge in our department. At
      admission to perform CAS, patients were assigned to normotensive, valsartan
      (hypertensive patients treated with valsartan with/without any kind of CCBs), and
      non-valsartan (hypertensive patients treated with any kind of CCBs without ARBs)
      groups. Post-CAS neointimal hyperplasia was evaluated by carotid duplex
      ultrasound imaging in terms of intima-media thickening (IMT), which was performed
      at pre-CAS and at 90, 180, 270, and 360 days post-CAS. Biomarkers of oxidative
      stress (8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein, tenascin
      C) and endothelial cell injury (von Willebrand factor [vWF] antigen) were
      measured at pre-CAS and at 1, 7, and 180 days post-CAS. RESULTS: The non
      valsartan group (n  =  8) had a higher incidence of maximum in-stent IMT ? 1.1 mm
      compared with the normotensive group (n  =  6). Valsartan (n  =  9) significantly
      suppressed plasma vWF levels at 7 days post-CAS and decreased the incidence of
      maximum in-stent IMT ? 1.1 mm compared with the non-valsartan group, although
      clinical parameters were similar between the two groups. Other biomarkers were
      not significantly different among the three groups. CONCLUSIONS: These findings
      suggest that valsartan may prevent post-CAS neointimal hyperplasia possibly by
      suppressing endothelial cell injury.

PMID- 24938322
TI  - Informed consent and ECT: how much information should be provided?
AB  - Obtaining informed consent before providing treatment is a routine part of modern
      clinical practice. For some treatments, however, there may be disagreement over
      the requirements for 'informed' consent. Electroconvulsive therapy (ECT) is one
      such example. Blease argues that patients 'should surely be privy to the matters
      of fact that: (1) there is continued controversy over the effectiveness of ECT;
      (2) there is orthodox scientific consensus that there is currently no
      acknowledged explanation for ECT and (3) there is a serious (mainstream) debate
      over whether the response to ECT may be a placebo response.' Before embracing
      these suggestions, two key questions must be asked. Are these claims a reasonable
      representation of current ECT research? And if so, will this information be of
      benefit to patients? The evidence-based support for ECT from both National
      Institute for Health and Care Excellence and the Royal College of Psychiatrists
      appears to undermine the validity of claims (1) and (3), and therefore the
      rationale for providing this information. Concerning assertion (2), it is true
      that the mechanism by which ECT has its therapeutic effect is not yet
      established, although the importance of conveying this fact to the patient is
      questionable. Of greater certainty is that the same irresolution surrounds the
      mechanism of action of pharmaceutical antidepressants, and so a double standard
      in patient care should be mindfully avoided if provision of this information is
      deemed a prerequisite for proper 'informed' consent. 

PMID- 24938323
TI  - Detection of total and PRRSV-specific antibodies in oral fluids collected with
      different rope types from PRRSV-vaccinated and experimentally infected pigs.
AB  - BACKGROUND: Oral fluid collected by means of ropes has the potential to replace
      serum for monitoring and surveillance of important swine pathogens. Until now,
      the most commonly used method to collect oral fluid is by hanging a cotton rope
      in a pen. However, concerns about the influence of rope material on subsequent
      immunological assays have been raised. In this study, we evaluated six different
      rope materials for the collection of oral fluid and the subsequent detection of
      total and PRRSV-specific antibodies of different isotypes in oral fluid collected
      from PRRSV-vaccinated and infected pigs. RESULTS: An initial experiment showed
      that IgA is the predominant antibody isotype in porcine saliva. Moreover, it was
      found that synthetic ropes may yield higher amounts of IgA, whereas all rope
      types seemed to be equally suitable for IgG collection. Although IgA is the
      predominant antibody isotype in porcine oral fluid, the PRRSV-specific IgA-based
      IPMA and ELISA tests were clearly not ideal for sensitive detection of PRRSV
      specific IgA antibodies. In contrast, PRRSV-specific IgG in oral fluids was
      readily detected in PRRSV-specific IgG-based IPMA and ELISA tests, indicating
      that IgG is a more reliable isotype for monitoring PRRSV-specific antibody
      immunity in vaccinated/infected animals via oral fluids with the currently
      available tests. CONCLUSIONS: Since PRRSV-specific IgG detection seems more
      reliable than PRRSV-specific IgA detection for monitoring PRRSV-specific antibody
      immunity via oral fluids, and since all rope types yield equal amounts of IgG, it
      seems that the currently used cotton ropes are an appropriate choice for sample
      collection in PRRSV monitoring.

PMID- 24938326
TI  - Health services for Aboriginal and Torres Strait Islander people: handle with
      care.

PMID- 24938324
TI  - The inverse agonist propranolol confers no corticosteroid-sparing activity in
      mild-to-moderate persistent asthma.
AB  - The murine asthma model shows that switching off airway beta2 receptors with an
      inverse agonist may confer anti-inflammatory effects as well as corticosteroid
      sparing activity. We have assessed for any corticosteroid-sparing effects of
      propranolol, an inverse agonist, added to low-dose inhaled corticosteroid (ICS)
      compared with higher dose ICS. A randomized double-blind placebo-controlled cross
      over trial in mild-to-moderate persistent asthmatic patients was performed. After
      a run-in (2 weeks) on hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) at
      100 MUg/day (HFA-BDP100), patients received randomized treatments (4 weeks) with
      propranolol at 80 mg/day plus HFA-BDP at 100 MUg/day compared with placebo plus
      HFA-BDP at 400 MUg/day (HFA-BDP400). Propranolol was up-titrated to 80 mg/day
      over the initial 2 weeks. Tiotropium was co-administered until 5 days before each
      histamine challenge (the primary outcome). Sixteen patients completed the study
      [mean age, 38 years; forced expiratory volume in 1 s (FEV1), 86.4%; histamine
      provocative concentration causing a 20% fall in FEV1 (PC20), 1.39 mg/ml; ICS
      dose, 406 MUg/day]. Histamine PC20 was unchanged by adding propranolol to HFA
      BDP100 compared with baseline (HFA-BDP100) {0.17 doubling dilution (dd)
      difference [95% confidence interval (CI): -0.58 to 0.92]}, but there was a
      significant improvement with HFA-BDP400 compared with both baseline [1.05 dd (95%
      CI: 0.43-1.66); P=0.02], and propranolol+HFA-BDP100 [0.88 dd (95% CI: 0.45-1.30);
      P=0.006]. Significant improvements were also observed with HFA-BDP400 for exhaled
      nitric oxide, blood eosinophils, serum eosinophilic cationic protein and asthma
      quality-of-life questionnaire symptoms compared with propranolol+HFA-BDP100.
      Salbutamol recovery post-challenge was partially blunted by propranolol (median
      prolongation 5 min; P=0.002). Domiciliary evening FEV1 also fell with
      propranolol+HFA-BDP100 [mean reduction from baseline 0.22 litres (95% CI: 0.10
      0.34); P=0.012], whereas Asthma Control Questionnaire remained unchanged. In
      conclusion, the inverse agonist propranolol produced no improvements when given
      with low-dose ICS, whereas further significant improvements in airway hyper
      responsiveness and inflammation were demonstrated with higher dose ICS. Thus,
      propranolol does not confer corticosteroid-sparing activity in persistent asthma.

PMID- 24938327
TI  - Racism, health and constitutional recognition.

PMID- 24938328
TI  - The imperative for investment in Aboriginal and Torres Strait Islander health.

PMID- 24938329
TI  - The shape of things to come: visions for the future of Aboriginal and Torres
      Strait Islander health research.

PMID- 24938331
TI  - Indigenous health: radical hope or groundhog day?

PMID- 24938332
TI  - From vision to reality: a centre of excellence for Aboriginal and Torres Strait
      Islander primary health care.

PMID- 24938334
TI  - 2014 Australian medical association national conference.

PMID- 24938333
TI  - Decolonising practices: can journalism learn from health care to improve
      Indigenous health outcomes?

PMID- 24938335
TI  - Can we sustain health spending?

PMID- 24938336
TI  - Reports indicate that changes are needed to close the gap for Indigenous health.

PMID- 24938337
TI  - Reports indicate that changes are needed to close the gap for Indigenous health.

PMID- 24938338
TI  - Engaging Aboriginal and Torres Strait Islander men in primary care settings.

PMID- 24938339
TI  - Crusted scabies: a clinical marker of human T-lymphotropic virus type 1 infection
      in central Australia.

PMID- 24938340
TI  - Partial foot amputations may not always be worth the risk of complications.

PMID- 24938341
TI  - Partial foot amputations may not always be worth the risk of complications.

PMID- 24938342
TI  - Partial foot amputations may not always be worth the risk of complications.

PMID- 24938343
TI  - Off-label prescribing.

PMID- 24938344
TI  - A framework for overcoming disparities in management of acute coronary syndromes
      in the Australian Aboriginal and Torres Strait Islander population. A consensus
      statement from the National Heart Foundation of Australia.
AB  - Aboriginal and Torres Strait Islander patients with acute coronary syndromes
      (ACS) experience lower intervention rates and poorer outcomes compared with non
      Indigenous patients. A broad range of geographical, cultural and systemic factors
      contribute to delays and suboptimal treatment for ACS. Every Indigenous ACS
      patient, regardless of where they live, should be able to expect a coordinated,
      patient-centred pathway of care provided by designated provider clinical networks
      and supported by Indigenous cardiac coordinators, Aboriginal liaison officers
      (ALOs) and health workers. These designated provider clinical networks provide:
      appropriate prehospital and inhospital treatment an individualised patient care
      plan developed jointly with the patient and his or her family culturally
      appropriate education initiated within the hospital setting and involving
      families with support from ALOs effective follow-up care and access to relevant
      secondary prevention programs. We outline generic pathways to provide
      policymakers, health planners and health care providers with a framework for ACS
      diagnosis and management that can be implemented across the diverse settings in
      which Aboriginal and Torres Strait Islander people reside and their care is
      delivered, in order to optimise care and assertively address the current
      disparities in outcomes. 

PMID- 24938345
TI  - Crusted scabies in remote Australia, a new way forward: lessons and outcomes from
      the East Arnhem Scabies Control Program.
AB  - Crusted scabies is a highly infectious, debilitating and disfiguring disease, and
      remote Aboriginal communities of northern Australia have the highest reported
      rates of the condition in the world. We draw on monitoring data of the East
      Arnhem Scabies Control Program to discuss outcomes and lessons learnt through
      managing the condition in remote communities. Using active case finding, we
      identified seven patients with crusted scabies in three communities and found
      most had not presented to health services despite active disease. We compared
      presentations and hospitalisations for a cumulative total of 99 months during a
      novel preventive program with 99 months immediately before the program for the
      seven cases and seven sentinel household contacts. Our preventive long-term case
      management approach was associated with a significant 44% reduction in episodes
      of recurrent crusted scabies (from 36 to 20; P = 0.025) in the seven cases, and a
      non-significant 80% reduction in days spent in hospital (from 173 to 35; P =
      0.09). It was also associated with a significant 75% reduction in scabies-related
      presentations (from 28 to 7; P = 0.017) for the seven sentinel household
      contacts. We recommend active surveillance and wider adoption of this preventive
      case management approach, with ongoing evaluation to refine protocols and improve
      efficiency. Contacts of children presenting with recurrent scabies should be
      examined to exclude crusted scabies. In households where crusted scabies is
      present, a diagnosis of parental neglect due to recurrent scabies and weight loss
      in children should be made with extreme caution. Improved coordination of care by
      health services, and research and development of new therapies including
      immunotherapies for crusted scabies, must be a priority.

PMID- 24938346
TI  - Aboriginal community controlled health services: leading the way in primary care.
AB  - The national Closing the Gap framework commits to reducing persisting
      disadvantage in the health of Aboriginal and Torres Strait Islander people in
      Australia, with cross-government-sector initiatives and investment. Central to
      efforts to build healthier communities is the Aboriginal community controlled
      health service (ACCHS) sector; its focus on prevention, early intervention and
      comprehensive care has reduced barriers to access and unintentional racism,
      progressively improving individual health outcomes for Aboriginal people. There
      is now a broad range of primary health care data that provides a sound evidence
      base for comparing the health outcomes for Indigenous people in ACCHSs with the
      outcomes achieved through mainstream services, and these data show: models of
      comprehensive primary health care consistent with the patient-centred medical
      home model; coverage of the Aboriginal population higher than 60% outside major
      metropolitan centres; consistently improving performance in key performance on
      best-practice care indicators; and superior performance to mainstream general
      practice. ACCHSs play a significant role in training the medical workforce and
      employing Aboriginal people. ACCHSs have risen to the challenge of delivering
      best-practice care and there is a case for expanding ACCHSs into new areas. To
      achieve the best returns, the current mainstream Closing the Gap investment
      should be shifted to the community controlled health sector. 

PMID- 24938347
TI  - Follow-up of Indigenous-specific health assessments - a socioecological analysis.
AB  - OBJECTIVES: To describe patterns of uptake of Indigenous-specific health
      assessments and associated follow-up items, and examine the barriers and enablers
      to delivery and billing of follow-up over the first 3 years of implementation of
      the Indigenous Chronic Disease Package (ICDP). DESIGN, SETTING AND PARTICIPANTS:
      We used a socioecological approach to analyse data derived from the Sentinel
      Sites Evaluation of the ICDP - with data from 24 sites across Australia.
      Administrative data (1 May 2009 to 30 May 2012) and program data (1 March 2010 to
      30 May 2012) were provided by the Department of Health. Data on barriers and
      enablers to follow-up of health assessments were obtained from community focus
      groups, in-depth interviews and discussions with key informants (1 November 2010
      to 30 December 2012). MAIN OUTCOME MEASURES: Monthly number of Medicare Benefits
      Schedule items claimed for Indigenous-specific health services and follow-up;
      qualitative data on enablers and barriers categorised according to patient,
      patient-health service relationship, health service or organisation, community
      and policy environment levels or influence. RESULTS: There was an increase in the
      uptake of health assessments, but relatively limited delivery of follow-up care
      and billing for Indigenous-specific follow-up items. Follow-up was constrained by
      factors that operated at various levels: patient, interpersonal, health service,
      community and policy. Constraints included practitioners' lack of awareness of
      item numbers, staffing, poor state of clinical information systems, billing
      against non-Indigenous-specific items or more general follow-up items, emphasis
      on health assessments with less attention to requirements for follow-up, limited
      capacity to arrange and facilitate follow-up, and communication and transport
      challenges for patients. CONCLUSIONS: Work is required across various levels of
      the system to address barriers to follow-up care. Enhancing follow-up care is
      vital to achieving health benefits from the large financial and human resource
      investment in health assessments.

PMID- 24938348
TI  - The cost-effectiveness of primary care for Indigenous Australians with diabetes
      living in remote Northern Territory communities.
AB  - OBJECTIVE: To evaluate the costs and health outcomes associated with primary care
      use by Indigenous people with diabetes in remote communities in the Northern
      Territory. DESIGN, SETTING AND PARTICIPANTS: A population-based retrospective
      cohort study from 1 January 2002 to 31 December 2011 among Indigenous NT
      residents >= 15 years of age with diabetes who attended one of five hospitals or
      54 remote clinics in the NT. MAIN OUTCOME MEASURES: Hospitalisations, potentially
      avoidable hospitalisations (PAH), mortality and years of life lost (YLL).
      Variables included disease stage (new, established or complicated cases) and
      primary care use (low, medium or high). RESULTS: 14 184 patients were eligible
      for inclusion in the study. Compared with the low primary care use group, the
      medium-use group (patients who used primary care 2-11 times annually) had lower
      rates of hospitalisation, lower PAH, lower death rates and fewer YLL. Among
      complicated cases, this group showed a significantly lower mean annual
      hospitalisation rate (1.2 v 6.7 per person [P < 0.001]) and PAH rate (0.72 v 3.64
      per person [P < 0.001]). Death rate and YLL were also significantly lower (1.25 v
      3.77 per 100 population [P < 0.001] and 0.29 v 1.14 per person-year [P < 0.001],
      respectively). The cost of preventing one hospitalisation for diabetes was $248
      for those in the medium-use group and $739 for those in the high-use group. This
      compares to $2915, the average cost of one hospitalisation. CONCLUSION: Improving
      access to primary care in remote communities for the management of diabetes
      results in net health benefits to patients and cost savings to government.

PMID- 24938349
TI  - Cost of best-practice primary care management of chronic disease in a remote
      Aboriginal community.
AB  - OBJECTIVE: To estimate the cost of completing all chronic care tasks recommended
      by the Central Australian Rural Practitioners Association Standard Treatment
      Manual (CARPA STM) for patients with type 2 diabetes and chronic kidney disease
      (CKD). DESIGN AND SETTING: The study was conducted at a health service in a
      remote Central Australian Aboriginal community between July 2010 and May 2011.
      The chronic care tasks required were ascertained from the CARPA STM. The clinic
      database was reviewed for data on disease prevalence and adherence to CARPA STM
      guidelines. Recommended tasks were observed in a time-and-motion study of
      clinicians' work. Clinicians were interviewed about systematic management and its
      barriers. Expenditure records were analysed for salary and administrative costs.
      MAIN OUTCOME MEASURES: Diabetes and CKD prevalence; time spent on chronic disease
      care tasks; completion of tasks recommended by the CARPA STM; barriers to
      systematic care identified by clinicians; and estimated costs of optimal primary
      care management of all residents with diabetes or CKD. RESULTS: Projected annual
      costs of best-practice care for diabetes and CKD for this community of 542 people
      were $900 792, of which $645 313 would be met directly by the local primary care
      service. Estimated actual expenditure for these conditions in 2009-10 was $446
      585, giving a projected funding gap of $198 728 per annum, or $1733 per patient.
      High staff turnover, acute care workload and low health literacy also hindered
      optimal chronic disease care. CONCLUSION: Barriers to optimal care included
      inadequate funding and workforce issues. Reduction of avoidable hospital
      admissions and overall costs necessitates adequate funding of primary care of
      chronic disease in remote communities.

PMID- 24938350
TI  - Temporal trends in weight and current weight-related behaviour of Australian
      Aboriginal school-aged children.
AB  - OBJECTIVES: To report 13-year trends in weight status of Australian Aboriginal
      children, and to describe weight-related behaviour in children in 2010, by
      Aboriginality. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional population
      surveys of children aged 5-16 years (n = 18 983) conducted in New South Wales
      schools in Term 1 of 1997, 2004 and 2010. MAIN OUTCOME MEASURES: For trend
      analysis: body mass index and waist-to-height ratio (WtHr). Analyses of weight
      related behaviour from 2010 survey data included indicators of dietary habits,
      screen time (ST) and physical activity. RESULTS: Between 1997 and 2010, the
      relative increase in prevalence of overweight/obesity and WtHr >= 0.5 was 22.4%
      and 113.6%, respectively, among Aboriginal children, and 11.8% and 3.4%,
      respectively, among non-Aboriginal children. In 2010, Aboriginal children had
      1.52 (95% CI, 1.03-2.24) greater odds of having a WtHr >= 0.5 than non-Aboriginal
      children. Compared with non-Aboriginal children, Aboriginal children also had
      significantly lower odds of eating breakfast daily (adjusted odds ratio [AOR],
      0.72; 95% CI, 0.52-0.99) and significantly greater odds of drinking >= 1 cup of
      soft drink daily (AOR, 1.61; 95% CI, 1.13-2.29), having a television in their
      bedroom (AOR, 2.75; 95% CI, 2.04-3.70), having no ST rules (AOR, 1.34; 95% CI,
      1.04-1.73) and exceeding ST recommendations on weekdays (AOR, 1.78; 95% CI, 1.32
      2.39). CONCLUSIONS: Overweight/obesity and WtHr have increased more rapidly in
      Aboriginal than non-Aboriginal children in NSW. Unhealthy weight-related
      behaviour was frequent among all children, but lack of daily breakfast, excessive
      ST and soft drink consumption appear particularly problematic among Aboriginal
      children. Raising awareness with families of the consequences of excessive ST and
      encouraging strategies to limit ST (such as rethinking placement of televisions
      in children's bedrooms and implementing ST rules) hold promise.

PMID- 24938351
TI  - Spiralling into the nephrotic syndrome.

PMID- 24938352
TI  - What can circle sentencing courts tell us about drug and alcohol problems
      affecting Aboriginal communities?

PMID- 24938354
TI  - Scores on Riley's stuttering severity instrument versions three and four for
      samples of different length and for different types of speech material.
AB  - Riley stated that the minimum speech sample length necessary to compute his
      stuttering severity estimates was 200 syllables. This was investigated.
      Procedures supplied for the assessment of readers and non-readers were examined
      to see whether they give equivalent scores. Recordings of spontaneous speech
      samples from 23 young children (aged between 2 years 8 months and 6 years 3
      months) and 31 older children (aged between 10 years 0 months and 14 years 7
      months) were made. Riley's severity estimates were scored on extracts of
      different lengths. The older children provided spontaneous and read samples,
      which were scored for severity according to reader and non-reader procedures.
      Analysis of variance supported the use of 200-syllable-long samples as the
      minimum necessary for obtaining severity scores. There was no significant
      difference in SSI-3 scores for the older children when the reader and non-reader
      procedures were used. Samples that are 200-syllables long are the minimum that is
      appropriate for obtaining stable Riley's severity scores. The procedural variants
      provide similar severity scores.

PMID- 24938353
TI  - Should Aboriginals in the "Top End" of the Northern Territory be vaccinated
      against hepatitis A? 1994.

PMID- 24938355
TI  - An inflammatory myofibroblastic tumor exhibiting immunoreactivity to KIT: a case
      report focusing on a diagnostic pitfall.
AB  - Inflammatory myofibroblastic tumors (IMTs) and gastrointestinal stromal tumors
      (GISTs) are both spindle cell tumors, and occur rarely in the wall of the urinary
      bladder. In general, immunostaining allows differentiation of IMTs and GISTs.
      Most IMTs are positive for anaplastic lymphoma kinase (ALK) and negative for KIT,
      whereas most GISTs are ALK-negative and KIT-positive. Here, we describe a case of
      a spindle cell tumor in the wall of the urinary bladder. The spindle cells were
      positive for both ALK and KIT, and it was thus difficult to determine whether the
      tumor was an IMT or a GIST. We eventually diagnosed an IMT, because ALK gene
      rearrangement was confirmed by fluorescent in-situ hybridization. Cytoplasmic
      staining for KIT and the absence of other GIST markers, including DOG1 and
      platelet-derived growth factor alpha, indicated that the tumor was not a GIST.
      Therefore, IMTs should be included in the differential diagnosis of spindle cell
      tumors, even those that are KIT-positive. 

PMID- 24938356
TI  - Curcumin suppresses proliferation and invasion in non-small cell lung cancer by
      modulation of MTA1-mediated Wnt/beta-catenin pathway.
AB  - Curcumin, a naturally occurring phenolic compound, has a diversity of antitumor
      activities. It has been previously demonstrated that curcumin can inhibit the
      invasion and metastasis of tumors through activation of the tumor suppressor DnaJ
      like heat shock protein 40 (HLJ1). However, the specific roles and mechanisms of
      curcumin in regulating the malignant behaviors of non-small cell lung cancer
      (NSCLC) cells still remain unclear. In this study, we found that curcumin could
      inhibit the proliferation and invasion of NSCLC cells and induce G0/G1 phase
      arrest. Metastasis-associated protein 1 (MTA1) overexpression has been detected
      in a wide variety of aggressive tumors and plays an important role on cell
      invasion and metastasis. Our results showed that curcumin could effectively
      inhibit the MTA1 expression of NSCLC cells. Further research on the subsequent
      mechanism showed that curcumin inhibited the proliferation and invasion of NSCLC
      cells through MTA1-mediated inactivation of Wnt/beta-catenin pathway. Wnt/beta
      catenin signaling was reported to play a critical cooperative role on promoting
      lung tumorigenesis. Thus, these investigations provided novel insights into the
      mechanisms of curcumin on inhibition of NSCLC cell growth and invasion and showed
      potential therapeutic strategies for NSCLC. 

PMID- 24938357
TI  - 1alpha,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells
      through down-regulation of HBp17/FGFBP-1.
AB  - Heparin-binding protein 17/fibroblast growth factor binding protein-1
      (HBp17/FGFBP-1, GenBank accession no. NP-005121) is prominent for its role as the
      chaperone for fibroblast growth factor-2 (FGF-2), which plays a crucial role in
      angiogenesis as well as promoting tumor growth. HBp17/FGFBP-1 has been proposed
      as a candidate biomarker for a number of cancers since it is frequently found to
      be elevated in many cancer types including in the tissue and cell lines of oral
      squamous cell carcinomas (OSCC). Previously, we reported that 1alpha,25(OH)2D3
      suppressed the HBp17/FGFBP-1 expression in OSCC by inhibiting nuclear factor
      kappaB (NF-kappaB) expression via vitamin D3 receptor (VDR). In this paper, to
      further characterize the inhibitory effect of 1alpha,25(OH)2D3 on HBp17/FGFBP-1,
      we examined the cellular localization of HBp17/FGFBP-1 protein and FGF-2 protein
      in the UE OSCC cell line. We found that the treatment of OSCC cells with 40-nM
      1alpha,25(OH)2D3 suppressed HBp17/FGFBP-1 expression both in the nucleus and
      cytosol and reduced FGF-2 release into the culture medium. The expression of
      HBp17/FGFBP-1 and FGF-2 was analyzed by immunofluorescence and enzyme-linked
      immunosorbent assay (ELISA). In summary, the ability of 1alpha,25(OH)2D3 to
      suppress the expression of HBp17/FGFBP-1 and FGF-2 strongly suggests a
      therapeutic potential as a molecular-targeted anticancer drug for FGF-dependent
      cancers. 

PMID- 24938358
TI  - The co-localization of HBx and COXIII upregulates COX-2 promoting HepG2 cell
      growth.
AB  - HBx is a multifunctional regulator that interacts with host factors to contribute
      to the development of hepatocellular carcinoma. In this study, to explore the co
      localization of HBx and COXIII in HepG2 cells and to investigate the molecular
      mechanism of HBx in HepG2 cell growth promotion, we first constructed a HepG2
      cell line stably expressing the HBx gene in vitro by lentivirus vectors. In
      addition, we found that HBx co-localized with the inner mitochondrial protein,
      COXIII, in HepG2 cells by confocal laser scanning microscopy. It led to changes
      of mitochondrial biogenesis and morphology, including upregulation of COXIII
      protein expression, increased cytochrome c oxidase activity and higher
      mitochondrial membrane potential. The upregulation of COX-2 caused by HBx through
      generation of mitochondrial reactive oxygen species promoted cell growth. Thus,
      we conclude that co-localization of HBx and COXIII leads to upregulation of COX-2
      that promotes HepG2 cell growth. Such a mechanism provides deeper insights into
      the molecular mechanism of HBV-associated hepatocellular carcinoma.

PMID- 24938359
TI  - Prevalence and risk factors of overweight and obesity among individuals over 40
      years old in Luzhou city.
AB  - In this study, a survey was conducted through questionnaire distribution and
      physical examinations were performed in 10,150 residents that were over 40 years
      old in Luzhou city. Respondents were selected by the multi-stage sampling method.
      The mean body mass index (BMI) of the sample population was 23.9 +/- 3.3 kg/m(2).
      Among men, BMI showed a negative relationship with increasing age (P < 0.05),
      whereas among women, it showed a positive relationship (P < 0.001). The rates of
      overweight and obesity increased with age and reached a peak between 60 to 70
      years of age (P < 0.001). The rates of overweight and obesity varied with
      different working conditions, training situations, educational levels, marital
      status, and other factors (P < 0.05). Age, educational level, daily sitting time,
      and family history of diabetes were factors that influenced the prevalence of
      overweight and obesity through multivariate logistic regression analysis (P <
      0.05). The incidences of overweight and obesity among the middle-aged population
      were found to be significantly high. Therefore, prevention and control measures
      should be adopted as soon as possible. 

PMID- 24938360
TI  - Development of a high-yield technique to isolate spermatogonial stem cells from
      porcine testes.
AB  - PURPOSE: To date, the methods available for isolating spermatogonial stem cells
      (SSCs) from porcine testicular cells have a low efficiency of cell separating.
      Therefore, we tried to develop a novel isolation technique with a high-yield cell
      separating ability to isolate SSCs from porcine testes. METHODS: We confirmed the
      presence of SSCs by measuring alkaline phosphatase (AP) activity and SSC-specific
      gene expression in neonatal porcine testis-derived testicular cells.
      Subsequently, the isolation of SSCs from testicular cells was performed using
      different techniques as follows: differential plating (DP), double DP, Petri dish
      plating post-DP, magnetic-activated cell sorting (MACS), and MACS post-DP.
      Positive AP staining was used to assess and compare the isolation efficiency of
      each method. RESULTS: Petri dish plating post-DP resulted in the highest
      isolation efficiency. The putative SSCs isolated using this method was then
      further characterized by analyzing the expression of SSC-specific genes and 
      related proteins, and germ cell-specific genes. OCT4, NANOG, EPCAM, THY1, and
      UCHL1 were expressed transcriptionally, and OCT4, NANOG, SOX2, TRA-1-60, TRA-1
      81, and PLZF were expressed translationally in 86 % of the isolated SSCs. In
      contrast, no difference was observed in the percentage of cells expressing
      luteinizing hormone receptor (LHR), a Leydig cell-specific protein, or GATA4, a
      Sertoli cell-specific protein, between SSCs and negative control cells. In
      addition, transcriptional expression of VASA, a primordial germ cell-specific
      marker, and DAZL, a premeiotic germ cell-specific marker, wasn't and was
      detected, respectively. CONCLUSIONS: We successfully developed a novel high-yield
      technique to isolate SSCs from porcine testes to facilitate future porcine SSC
      related research.

PMID- 24938361
TI  - Developmental competence and expression pattern of bubaline (Bubalus bubalis)
      oocytes subjected to elevated temperatures during meiotic maturation in vitro.
AB  - OBJECTIVE: To determine the direct effect of physiologically relevant high
      temperatures (40.5 and 41.5  degrees C) for two time periods (12 and 24 h) on
      bubaline oocytes during in vitro maturation. METHOD: The control group oocytes
      were cultured at 38.5  degrees C for 24 h. The treatment 1 (T1) and 3 (T3) group
      oocytes were cultured at 40.5 and 41.5  degrees C respectively, for the first 12
      h and at 38.5  degrees C for rest of the 12 h. However, treatment 2 (T2) and 4
      (T4) group oocytes were cultured at 40.5 and 41.5  degrees C for complete 24 h.
      RESULTS: Development of oocytes to blastocyst was severely compromised (p <
      0.001) when matured at 40.5 and 41.5  degrees C for both exposure periods (12 h
      and 24 h). It was found that the cleavage rates, blastocyst yield and mean cell
      number decreased remarkably (p < 0.001) in the treatment groups compared to
      control. The relative mRNA expression of heat shock protein (Hsp 70.1, 70.2,
      70.8, 60, 10 and HSF1), pro-apoptotic (caspases-3, -7, -8, Bid and Bax) and
      oxidative stress (iNOS) related genes was significantly higher (p < 0.05) in all
      the treatment groups compared to control. However, mRNA abundance of anti
      apoptotic (Bcl-2, Mcl-1, Bcl-xl), glucose transport (Glut1, Glut3 and IGF1R),
      developmental competence (ZAR1 and BMP15) and oxidative stress (MnSOD) related
      genes was significantly decreased (p < 0.05) in the treatment groups compared to
      control. CONCLUSION: The present study clearly establishes that physiologically
      relevant elevated temperatures during in vitro meiotic maturation reduce
      developmental competence of bubaline oocytes.

PMID- 24938364
TI  - The ethical, legal and human rights concerns raised by licensing HIV self-testing
      for private use.
AB  - We argue that there are no compelling ethical grounds for not allowing the sale
      of HIV self-tests to the public, so long as reasonably robust protections are in
      place to protect against coerced testing, and so long as the ease of use of the
      test is validated carefully in each country in which it is used, with attention
      to information about linkage to treatment, social and psychological support. The
      tests are not likely to be harmful in a way that justifies restricting people's
      access to them, and have plausible benefits. Whether and how self-testing should
      be used in public health programs will depend on complex policy questions
      concerning priorities, efficacy and cost. 

PMID- 24938363
TI  - TOPLESS mediates brassinosteroid-induced transcriptional repression through
      interaction with BZR1.
AB  - Brassinosteroid (BR) regulates plant development by activating the transcription
      factor brassinazole resistant 1 (BZR1), which activates and represses different
      target genes to switch cellular programmes. The mechanisms that determine BZR1's
      transcriptional activities remain largely unknown. Here we show that BZR1
      represses target genes by recruiting the Groucho/TUP1-like transcriptional
      corepressor TOPLESS (TPL). Specific deletion or mutation of an evolutionarily
      conserved ERF-associated amphiphilic repression (EAR) motif at the carboxy
      terminus abolishes BZR1's abilities to regulate gene expression and cell
      elongation, but these defects are rescued by TPL fusion to the EAR motif-mutated
      BZR1. The EAR motif in BZR1 mediates recruitment of TPL to BZR1-repressed
      promoters. A triple tpl mutant (tpl;tpr1;tpr4) shows reduced BR sensitivity and
      suppresses the gain-of-function bzr1-1D mutant phenotype. BR repression of gene
      expression also requires histone deacetylases that interact with TPL. Our study
      demonstrates key roles of the EAR motif and TPL in BR regulation of gene
      expression and plant growth. 

PMID- 24938365
TI  - [Trabeculotomy before the estimated delivery date. Case report of a preterm
      infant with buphthalamus].
AB  - Congenital glaucoma is a disease potentially leading to blindness in children. It
      poses a diagnostic and therapeutic challenge even though new knowledge has been
      acquired and a sufficient understanding of the pathogenesis has been gained. New
      discoveries, such as the exact time when Schlemm's canal develops could lead to a
      prenatal diagnosis and therefore surgical intervention so that other
      complications including blindness can be avoided. This case report demonstrates
      that an early prenatal eye screening with ultrasound (after approximately 30
      weeks of pregnancy) would be desirable in order to diagnose buphthalmus early and
      to plan postnatal surgery. 

PMID- 24938362
TI  - AMH in women with diminished ovarian reserve: potential differences by FMR1 CGG
      repeat level.
AB  - PURPOSE: We explored whether AMH, as a surrogate for oocyte supply, varies by
      FMR1 genotype in women diagnosed with diminished ovarian reserve (DOR), a subset
      of the Primary Ovarian Insufficiency phenotype. Research is inconsistent on the
      relationship between AMH and FMR1 repeat length, controlling for age. METHOD:
      Seventy-nine cycling women diagnosed with DOR, and without a family history of
      fragile X syndrome, provided blood for FMR1 and AMH testing. DOR was defined as
      elevated FSH and/or low AMH and/or low antral follicle count, with regular
      menses. FMR1 CGG repeats were stratified by the larger allele <35 repeats (n =
      70) v. >=35 repeats (n = 9). Quadratic and linear models were fit to predict log
      (AMH) controlling for age. The AMH sample used as the outcome variable was drawn
      at a later date than the diagnostic AMH. RESULTS: Serum AMH concentration median
      was 0.30 ng/mL; Ages ranged from 26-43 years. A quadratic model (including
      age(2)) did not show a relationship with FMR1 CGG level (p-value = 0.25). A
      linear model of log (AMH), corresponding to an exponential decline of AMH with
      increasing age, was significantly different, and had a steeper slope, for women
      with >= 35 CGG repeats than women with < 35 repeats (p = 0.035). CONCLUSION:
      Findings suggest a greater rate of follicular loss that starts at later ages in
      women with DOR and >= 35 CGG repeats.

PMID- 24938366
TI  - [Peracute corneal alterations and anterior chamber reaction following refractive
      surface ablation].

PMID- 24938367
TI  - [Choroidal tumor with accompanying papilledema].

PMID- 24938368
TI  - [Trauma-related secondary glaucoma in childhood: a therapeutic challenge].
AB  - CASE REPORT: We performed a minimally invasive trabeculotomy using a trabectome
      on a 9-year-old boy with a trauma-related secondary glaucoma where the
      intraocular pressure (IOP) could not be controlled by conservative approaches.
      After a 1-year follow-up the patient showed well controlled IOP values without
      using drugs to reduce pressure. CONCLUSION: Trabectome surgery seems to be a
      suitable first step intervention for trauma-related glaucoma in selected cases,
      even in children.

PMID- 24938370
TI  - Hyperactive antifreeze protein from an Antarctic sea ice bacterium Colwellia sp.
      has a compound ice-binding site without repetitive sequences.
AB  - Antifreeze proteins (AFPs) are structurally diverse macromolecules that bind to
      ice crystals and inhibit their growth to protect the organism from injuries
      caused by freezing. An AFP identified from the Antarctic bacterium Colwellia sp.
      strain SLW05 (ColAFP) is homologous to AFPs from a wide variety of psychrophilic
      microorganisms. To understand the antifreeze function of ColAFP, we have
      characterized its antifreeze activity and determined the crystal structure of
      this protein. The recombinant ColAFP exhibited thermal hysteresis activity of
      approximately 4  degrees C at a concentration of 0.14 mm, and induced rapid
      growth of ice crystals in the hexagonal direction. Fluorescence-based ice plane
      affinity analysis showed that ColAFP binds to multiple planes of ice, including
      the basal plane. These observations show that ColAFP is a hyperactive AFP. The
      crystal structure of ColAFP determined at 1.6 A resolution revealed an irregular
      beta-helical structure, similar to known homologs. Mutational and molecular
      docking studies showed that ColAFP binds to ice through a compound ice-binding
      site (IBS) located at a flat surface of the beta-helix and the adjoining loop
      region. The IBS of ColAFP lacks the repetitive sequences that are characteristic
      of hyperactive AFPs. These results suggest that ColAFP exerts antifreeze activity
      through a compound IBS that differs from the characteristic IBSs shared by other
      hyperactive AFPs. This study demonstrates a novel method for protection from
      freezing by AFPs in psychrophilic microorganisms. DATABASE: Structural data for
      ColAFP have been submitted to the Protein Data Bank (PDB) under accession number
      3WP9.

PMID- 24938372
TI  - Santonic acid: Zn-HCl-ether reduction and ceric ammonium nitrate oxidation.
AB  - Reduction of santonic acid using Zn-HCl-ether yielded succinic anhydride
      derivatives via pinacolisation followed by rearrangement, whereas oxidation of
      santonic acid using ceric ammonium nitrate afforded five oxidative
      decarboxylation products. Dedicated to Prof. TBH McMurry. 

PMID- 24938371
TI  - Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to
      schizophrenia and bipolar disorder: an updated meta-analysis.
AB  - Previous studies examining the possible role of the methylenetetrahydrofolate
      reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and
      bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis
      was therefore designed to get a more reliable assessment. A total of 38 articles
      were identified through a search of electronic databases, up to 27 February 2014.
      Odds ratios (ORs) with 95% confidence interval (CIs) were calculated using random
      effects models. Meta-analysis showed that MTHFR C677T was significantly
      associated with SZ, the highest OR was found for the recessive model (for TT vs.
      CT + CC: OR = 1.34, 95% CI: 1.18-1.53); a marginal association of MTHFR C677T
      with increased risk of BPD has also been found for the recessive model (OR =
      1.26, 95% CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the
      significant association with SZ and BPD existed among Asian and African
      populations, but not for the white. MTHFR A1298C was significant associated with
      SZ, the highest OR for the dominant model (OR = 1.13, 95% CI: 1.03-1.24).
      Subgroup analysis indicated a significant association with SZ existed in Asian
      populations, not among the white populations and no significant association was
      detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR
      polymorphism is associated with SZ and BPD among Asian, African populations, but
      not the white.

PMID- 24938369
TI  - Smoking cessation in smokers who smoke menthol and non-menthol cigarettes.
AB  - AIMS: To assess the relations of menthol cigarette use with measures of cessation
      success in a large comparative effectiveness trial (CET). DESIGN: Participants
      were randomized to one of six medication treatment conditions in a randomized
      double-blind, placebo-controlled clinical trial. All participants received six
      individual counseling sessions. SETTING: Community-based smokers in two
      communities in Wisconsin, USA. PARTICIPANTS: A total of 1504 adult smokers who
      smoked at least 10 cigarettes per day during the past 6 months and reported being
      motivated to quit smoking. The analysis sample comprised 1439 participants: 814
      white non-menthol smokers, 439 white menthol smokers and 186 African American
      (AA) menthol smokers. There were too few AA non-menthol smokers (n = 16) to be
      included in the analyses. INTERVENTIONS: Nicotine lozenge, nicotine patch,
      bupropion sustained release, nicotine patch + nicotine lozenge, bupropion +
      nicotine lozenge and placebo. MEASUREMENTS: Biochemically confirmed 7-day point
      prevalence abstinence assessed at 4, 8 and 26 weeks post-quit. FINDINGS: In
      longitudinal abstinence analyses (generalized estimating equations) controlling
      for cessation treatment, menthol smoking was associated with reduced likelihood
      of smoking cessation success relative to non-menthol smoking [model-based
      estimates of abstinence = 31 versus 38%, respectively; odds ratio (OR) = 0.71,
      95% confidence interval (CI) = 0.59, 0.86]. In addition, among menthol smokers,
      AA women were at especially high risk of cessation failure relative to white
      women (estimated abstinence = 17 versus 35%, respectively; OR = 2.63, 95% CI =
      1.75, 3.96; estimated abstinence rates for AA males and white males were both
      30%, OR = 1.06, 95% CI = 0.60, 1.66). CONCLUSION: In the United States, smoking
      menthol cigarettes appears to be associated with reduced cessation success
      compared with non-menthol smoking, especially in African American females.

PMID- 24938373
TI  - Selective ratiometric detection of H2O2 in water and in living cells with
      boronobenzo[b]quinolizinium derivatives.
AB  - Boronobenzo[b]quinolizinium derivatives exhibit several favorable properties for
      the fluorimetric detection of hydrogen peroxide, namely quantitative
      transformation to a product whose emission maximum is well separated from the one
      of the substrate, water solubility, and the ability to operate in living cells. 

PMID- 24938374
TI  - Myringoplasty using rotation flap of canal skin for total tympanic membrane
      perforation.
AB  - OBJECTIVE: To evaluate the efficacy of a novel technique of using rotation flap
      of canal skin in patients with total or subtotal tympanic membrane (TM)
      perforation with no anterior residual tympanic membrane. METHODS: A retrospective
      study of 50 patients with total or subtotal perforation repaired with rotation
      flap of canal skin. Clinical and audiometric data were recorded. RESULTS: The
      overall perforation closure rate was 96%. A statistically significant shortened
      healing time was observed. CONCLUSION: The rotation flap of canal skin could be
      an effective and safe technique for perforations with no anterior residual TM.

PMID- 24938375
TI  - ALDH1A1 expression correlates with clinicopathologic features and poor prognosis
      of breast cancer patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been
      identified as a putative cancer stem cell (CSC) marker in breast cancer. However,
      the clinicopathological and prognostic significance of this protein in breast
      cancer patients remains controversial. METHODS: This meta-analysis was conducted
      to address the above issues using 15 publications covering 921 ALDH1A1(+) cases
      and 2353 controls. The overall and subcategory analyses were performed to detect
      the association between ALDH1A1 expression and clinicopathological/prognostic
      parameters in breast cancer patients. RESULTS: The overall analysis showed that
      higher expression of ALDH1A1 is associated with larger tumor size, higher
      histological grade, greater possibility of lymph node metastasis (LNM), higher
      level expression of epidermal growth factor receptor 2 (HER2), and lower level
      expression of estrogen receptor (ER)/progesterone receptor (PR). The prognosis of
      breast cancer patients with ALDH1A1(+) tumors was poorer than that of the
      ALDH1A1(-) patients. Although the relationships between ALDH1A1 expression and
      some clinicopathological parameters (tumor size, LNM, and the expression of HER2)
      was not definitive to some degree when we performed a subcategory analysis, the
      predictive values of ALDH1A1 expression for histological grade and survival of
      breast cancer patients were significant regardless of the different cutoff values
      of ALDH1A1 expression, the different districts where the patients were located,
      the different clinical stages of the patients, the difference in antibodies used
      in the studies, and the surgery status. CONCLUSIONS: Our results indicate that
      ALDH1A1 is a biomarker to predict tumor progression and poor survival of breast
      cancer patients. This marker should be taken into consideration in the
      development of new diagnostic and therapeutic program for breast cancer.

PMID- 24938376
TI  - Pharmacies as providers of expanded health services for people who inject drugs:
      a review of laws, policies, and barriers in six countries.
AB  - BACKGROUND: People who inject drugs (PWID) are underserved by health providers
      but pharmacies may be their most accessible care settings. METHODS: Studies in
      the U.S., Russia, Vietnam, China, Canada and Mexico employed a three-level (macro
      , meso-, and micro-) model to assess feasibility of expanded pharmacy services
      for PWID. Studies employed qualitative and quantitative interviews, review of
      legal and policy documents, and information on the knowledge, attitudes, and
      practices of key stakeholders. RESULTS: Studies produced a mixed assessment of
      feasibility. Provision of information and referrals by pharmacies is permissible
      in all study sites and sale and safe disposal of needles/syringes by pharmacies
      is legal in almost all sites, although needle/syringe sales face challenges
      related to attitudes and practices of pharmacists, police, and other actors.
      Pharmacy provision of HIV testing, hepatitis vaccination, opioid substitution
      treatment, provision of naloxone for drug overdose, and abscess treatment, face
      more serious legal and policy barriers. DISCUSSION: Challenges to expanded
      services for drug users in pharmacies exist at all three levels, especially the
      macro-level characterized by legal barriers and persistent stigmatization of
      PWID. Where deficiencies in laws, policies, and community attitudes block
      implementation, stakeholders should advocate for needed legal and policy changes
      and work to address community stigma and resistance. Laws and policies are only
      as good as their implementation, so attention is also needed to meso- and micro-
      levels. Policies, attitudes, and practices of police departments and pharmacy
      chains as well as knowledge, attitudes, and practices of individual PWID,
      individual pharmacies, and police officers should support rather than undermine
      positive laws and expanded services. Despite the challenges, pharmacies remain
      potentially important venues for delivering health services to PWID.

PMID- 24938377
TI  - Role of tissue-specific AT-rich DNA sequence-binding proteins in lymphocyte
      differentiation.
AB  - A great many transcription factors, cytokines, and cytokine receptors have been
      identified as indispensable elements in lymphocyte differentiation, but the
      molecular mechanism that orchestrates the expression and function of these
      molecular factors is unknown. The process of lymphocyte differentiation involves
      both the simultaneous activation of lymphoid-related genes and the inactivation
      of non-lymphoid lineage-related genes, suggesting that there should be critical
      molecules that regulate such gene expression in both temporal and spatial
      dimensions. Recent studies of chromatin-remodeling proteins shed light on this
      complex process. In particular, special AT-rich sequence-binding protein 1 has
      been studied extensively. In this article, we review the wealth of information
      characterizing this protein. 

PMID- 24938378
TI  - Progress in the treatment of acute promyelocytic leukemia: optimization and
      obstruction.
AB  - The past three decades have witnessed a great progress in the treatment of acute
      promyelocytic leukemia (APL). The current application of all-trans retinoic acid,
      arsenic trioxide (ATO), and anthracycline-based chemotherapies has been proved to
      be highly effective. Based on the risk factors of APL, optimization of the
      treatment emphasizes the role of ATO in induction, consolidation and maintenance
      therapy as a substitute to chemotherapy in low- and intermediate-risk patients,
      and in potential reduction of chemotherapy in high-risk group without impact on
      the outcome. However, early death and relapse remain obstacles to further
      improvement of the rates of remission and long-term survival, and the acute and
      chronic adverse effects of ATO should be considered for more appropriate
      management. Efforts should be made to more rationally obtain improved outcomes
      through the use of less toxic regimens. 

PMID- 24938379
TI  - HIV-related NK/T-cell lymphoma in the brain relapsed during intensive
      chemotherapy but regressed after chemotherapy discontinuation: the importance of
      maintaining cellular immunity.
AB  - This study reports a case of human immunodeficiency virus (HIV)-related natural
      killer/T-cell lymphoma with an unexpected clinical course. The lymphoma cells
      were positive for Epstein-Barr virus and the primary nodal lesions regressed
      after chemotherapy and combined antiretroviral therapy (c-ART); however, brain
      metastasis progressed along with a reduction in the CD8+ T-cell count.
      Chemotherapy was discontinued and the patient was treated with c-ART alone,
      resulting in regression of the brain lesions and recovery of the CD8+ T-cell
      count. This case highlights the importance of maintaining anti-tumor immunity in
      patients with HIV-related lymphoma.

PMID- 24938380
TI  - Treatment outcomes of adolescent acute lymphoblastic leukemia treated on Tokyo
      Children's Cancer Study Group (TCCSG) clinical trials.
AB  - There is no standard treatment for adolescents aged 15 years or older with acute
      lymphoblastic leukemia (ALL), although this age group has been reported as having
      a poorer prognosis compared to younger patients. We retrospectively analyzed the
      outcomes of three consecutive Tokyo Children's Cancer Study Group ALL trials
      (1995-2006) of 373 patients aged 10 years or older, with particular focus on
      adolescents aged 15-18 years (older-adolescents n = 41), compared to those aged
      10-14 years (younger-adolescents n = 332). The probability of event-free survival
      at 8 years was 67.5 +/- 7.4 % for the older-adolescents and 66.5 +/- 2.6 % for
      the younger-adolescents (p = 0.95). Overall survival was 70.7 +/- 7.1 % for the
      older-adolescents and 74.3 +/- 2.4 % for the younger-adolescents (p = 0.48). The
      differences between groups in relapse incidence, non-relapse mortality, and death
      rate during induction were not statistically significant, although the older
      adolescents trended towards a higher frequency of having stem-cell
      transplantation during the first remission. In conclusion, our treatment
      strategy, which consists of intensive induction and block-type consolidation,
      provided improved outcomes for patients aged 15-18 years, comparable to those for
      patients aged 10-14 years.

PMID- 24938381
TI  - Online health information, situational effects and health changes among e
      patients in Israel: A 'push/pull' perspective.
AB  - BACKGROUND/CONTEXT: Access and use of online health information become
      increasingly important to health-oriented individual that may have implication
      for their health and wellness. The phenomenon of e-patients suggests that e
      patients use the internet to increase health literacy and achieve health
      information about diagnosis, treatments, specialists and well-being before
      undergoing a health changes. Online health information may not 'fit'
      consultations with providers mainly when online source of information is trusted
      mainly when e-patients express lack of satisfaction with health-care providers.
      The strain between the two becomes evident when e-patients consider health
      changes. OBJECTIVE: We examine health changes among e-patients. We assess the
      relationship between (a) trust in online health information and (b) satisfaction
      with health-care provider to predict two types of health changes: (a) well-being
      and (b) health-care changes. We also control for 'situational' effects including
      socio-economic and chronic illness variations. DESIGN: A telephone survey was
      conducted in 2010 in Israel among approximately 4000 individuals. SETTING AND
      PARTICIPANTS: Two-thousand individuals completed interviews (54% response rate).
      Seventy percentage were Internet users (n = 1371). MAIN VARIABLES: Well-being
      health changes; health-care changes; satisfaction with institutional health-care
      provider; chronic illness: socio-economic: age; gender; marital status;
      education. MAIN OUTCOME MEASURES: Socio-economic and health status differences
      generate variations in use of online health information; trusting online health
      positively affects well-being - not health-care - changes but satisfaction with
      health-care provider positively improves the likelihood for health-care changes.
      FINDINGS: The results indicate that (a) e-patients use online health information
      to make well-being health changes - starting a diet or physical activity
      programme - but not health-care changes - in medication or in health-care
      provider - (b) satisfaction with institutional health provider has a significant
      effect on health-care decisions (c) chronically ill are not likely to use online
      health information. DISCUSSION: E-patients' expectations from health-care
      institutional providers play a central role in initiating health changes. Access
      and use of online health information provide an alternative/additional channel
      for information when e-patients consider health changes and create a push/pull
      decision-making strain on both providers and recipients of health services.
      Health-care providers should address e-patients'concerns, mainly in cases of
      chronic illness concerns, and point to the boundaries of online health
      information. Traditional and novel sources of health information can increase
      health empowerment and better health care when communication channels between
      health providers and e-patients are comfortably verified in advance and agreed
      upon.

PMID- 24938384
TI  - Association of Lhermitte-Duclos disease and split cord malformation in a child.
AB  - Lhermitte-Duclos disease (LDD) or cerebellar gangliocytoma is a rare pathological
      entity, the etiology of which remains controversial. Numerous developmental
      anomalies are known to be associated with LDD, but the association between LDD
      and split cord malformation (SCM) has not been reported to our knowledge. We
      report LDD in a 3-year-old girl in whom repetitive urinary tract infections led
      to the diagnosis of a neurogenic bladder. Thorough screening revealed a SCM at
      the thoracic level which was surgically repaired. The pathogenesis of this entity
      and management strategies are discussed in this paper. 

PMID- 24938383
TI  - Cohort study on clustering of lifestyle risk factors and understanding its
      association with stress on health and wellbeing among school teachers in Malaysia
      (CLUSTer)--a study protocol.
AB  - BACKGROUND: The study on Clustering of Lifestyle risk factors and Understanding
      its association with Stress on health and wellbeing among school Teachers in
      Malaysia (CLUSTer) is a prospective cohort study which aims to extensively study
      teachers in Malaysia with respect to clustering of lifestyle risk factors and
      stress, and subsequently, to follow-up the population for important health
      outcomes. METHOD/DESIGN: This study is being conducted in six states within
      Peninsular Malaysia. From each state, schools from each district are randomly
      selected and invited to participate in the study. Once the schools agree to
      participate, all teachers who fulfilled the inclusion criteria are invited to
      participate. Data collection includes a questionnaire survey and health
      assessment. Information collected in the questionnaire includes socio-demographic
      characteristics, participants' medical history and family history of chronic
      diseases, teaching characteristics and burden, questions on smoking, alcohol
      consumption and physical activities (IPAQ); a food frequency questionnaire, the
      job content questionnaire (JCQ); depression, anxiety and stress scale (DASS21);
      health related quality of life (SF12-V2); Voice Handicap Index 10 on voice
      disorder, questions on chronic pain, sleep duration and obstetric history for
      female participants. Following blood drawn for predefined clinical tests,
      additional blood and urine specimens are collected and stored for future
      analysis. Active follow up of exposure and health outcomes will be carried out
      every two years via telephone or face to face contact. Data collection started in
      March 2013 and as of the end of March 2014 has been completed for four states:
      Kuala Lumpur, Selangor, Melaka and Penang. Approximately 6580 participants have
      been recruited. The first round of data collection and blood sampling is expected
      to be completed by the end of 2014 with an expected 10,000 participants
      recruited. DISCUSSION: Our study will provide a good basis for exploring the
      clustering of lifestyle risk factors and stress and its association with major
      chronic medical conditions such as obesity, hypertension, impaired glucose
      tolerance, diabetes mellitus, coronary heart diseases, kidney failure and cancers
      among teachers.

PMID- 24938385
TI  - Safe intravenous thrombolysis in acute stroke despite treatment with rivaroxaban.
AB  - Data regarding intravenous thrombolysis in stroke patients receiving new oral
      anticoagulant drugs (nOAC) is sparse. In the near future, however, an increasing
      number of patients with atrial fibrillation will suffer recurrent stroke despite
      treatment with nOAC. This will cause a significant therapeutic dilemma as
      thrombolysis is contraindicated under such circumstances. We describe an 81-year
      old patient presenting with acute ischemic stroke who was successfully treated
      with intravenous thrombolysis despite ongoing treatment with rivaroxaban. Our
      case report indicates that thrombolysis under nOAC may be safe under certain
      conditions and emphasizes the importance of establishing and performing specific
      anticoagulation tests for nOAC. 

PMID- 24938386
TI  - Efficacy of intraoperative vancomycin powder use in intrathecal baclofen pump
      implantation procedures: single institutional series in a high risk population.
AB  - We aimed to assess the efficacy of intraoperative vancomycin powder in
      intrathecal baclofen pump placement patients, a high risk population. A
      retrospective review was conducted using prospectively collected data at an
      academic tertiary care unit. The neurosurgical adult patient population was
      queried for all intrathecal baclofen pump implantation procedures. Patients were
      then reviewed for the use of intraoperative crystalline vancomycin powder. Those
      with a history of prior surgical site infection, chronic systemic infections or
      osteomyelitis were excluded. Anhydrous, crystalline vancomycin was utilized in
      the wound bed after completion of implantation, distributed evenly in the case of
      multiple incisions. Patients received 500 mg or 1,000 mg of crystallized
      vancomycin, evenly distributed through the wound layers based on a 70 kg weight
      cutoff. Intraoperative institutional standards of infection prophylaxis were
      unchanged throughout the study period. Infection rate of baclofen pump placement
      prior to the use of vancomycin powder from 2001-2009 at the same institution was
      monitored. Wound infection rate was tracked for a 12 month postoperative period.
      Six patients out of 26 baclofen pump implantations (23%) in this cohort were
      identified to have seven infections despite vancomycin powder placement in the
      lumbar and catheter wounds. Prior infection rates have been investigated for
      intrathecal drug delivery systems from 2001 to 2009 at the same institution with
      an overall infection rate of 3% (8/274). The use of vancomycin powder in patients
      with implants in this series did not reduce infection rates compared to published
      historical controls, and was elevated compared to institutional controls. Further
      prospective study of this high risk patient population is warranted.

PMID- 24938387
TI  - Microvascular decompression for recurrent trigeminal neuralgia.
AB  - Recurrence of trigeminal neuralgia (TN) symptoms after microvascular
      decompression (MVD) is a challenge for neurosurgeons. This study evaluates the
      indication, efficacy and safety of re-do MVD. We retrospectively reviewed
      consecutive patients who underwent MVD for TN from January 2000 to June 2012. The
      parameters of study interest were pre-operative magnetic resonance tomographic
      angiography (MRTA) findings and operative findings. Pain outcome was scored using
      the Barrow Neurological Institute (BNI) grading scale. Twelve patients underwent
      re-do MVD following recurrence of pain. Vascular compression was detected on pre
      operative MRTA images in eight patients, a small mass was found in two patients,
      and pre-operative imaging was negative in two patients. Of the eight patients
      with a positive finding of arterial conflict, a vascular loop was identified
      intra-operatively in five patients (62.5%); in two (25.0%) a small granuloma
      filled with Teflon fibers was found compressed the trigeminal nerve; and in one
      patient (12.5%) only dense arachnoid adhesions were found around the trigeminal
      nerve. For the two patients with mass compression on MRTA images, a granuloma was
      found during operation. Neurovascular compression was found in the two patients
      with negative preoperative MRTA images. Re-do MVD is a safe and effective
      treatment for recurrent TN when indicated by a prolonged pain-free period
      following the first surgery. 

PMID- 24938388
TI  - Posaconazole responsive cerebral aspergillosis in an immunocompetent adult.
AB  - Cerebral aspergillosis is a rare manifestation of invasive aspergillosis that
      usually affects immunocompromised patients. There are few treatment options for
      recurrent disease and experiences with immunocompetent patients are lacking. We
      report the clinical course of an immunocompetent patient with recurrent cerebral
      aspergillosis, following initial treatment with burr hole aspiration and
      voriconazole, who showed remarkable response to posaconazole. The patient remains
      clinically well with no evidence of recurrence on MRI 7 years following
      diagnosis. To our knowledge this is the first reported experience with
      posaconazole in an immunocompetent patient with cerebral aspergillosis.

PMID- 24938389
TI  - Pigmented villonodular synovitis of the thoracic spine.
AB  - Pigmented villonodular synovitis (PVNS) is a proliferative lesion of the synovial
      membranes. Knees, hips, and other large weight-bearing joints are most commonly
      affected. PVNS rarely presents in the spine, in particular the thoracic segments.
      We present a patient with PVNS in the thoracic spine and describe its clinical
      presentation, radiographic findings, pathologic features, and treatment as well
      as providing the first comprehensive meta-analysis and review of the literature
      on this topic, to our knowledge. A total of 28 publications reporting 56 patients
      were found. The lumbar and cervical spine were most frequently involved (40% and
      36% of patients, respectively) with infrequent involvement of the thoracic spine
      (24% of patients). PVNS affects a wide range of ages, but has a particular
      predilection for the thoracic spine in younger patients. The mean age in the
      thoracic group was 22.8 years and was significantly lower than the cervical and
      lumbar groups (42.4 and 48.6 years, respectively; p=0.0001). PVNS should be
      included in the differential diagnosis of osteodestructive lesions of the spine,
      especially because of its potential for local recurrence. The goal of treatment
      should be complete surgical excision. Although the pathogenesis is not clear,
      mechanical strain may play an important role, especially in cervical and lumbar
      PVNS. The association of thoracic lesions and younger age suggests that other
      factors, such as neoplasia, derangement of lipid metabolism, perturbations of
      humoral and cellular immunity, and other undefined patient factors, play a role
      in the development of thoracic PVNS.

PMID- 24938392
TI  - Assessing professional behaviour: Overcoming teachers' reluctance to fail
      students.
AB  - BACKGROUND: Developing professional behaviour is an important goal of medical
      education in which teachers play a significant part. Many teachers can be
      reluctant to fail students demonstrating unprofessional behaviour. We hypothesize
      that supporting teachers in teaching and assessing professional behaviour and
      involving them in remediation will reduce this reluctance. FINDINGS: In 2010,
      VUmc School of Medical Sciences Amsterdam introduced an educational theme on
      professional behaviour for the bachelor's and master's programmes in medicine
      with a special emphasis on supporting teachers in teaching and assessing
      professional behaviour and involving them in the remediation process. Information
      was extracted from the student database on the number of unprofessional behaviour
      judgments awarded over 2008-2010 (before the intervention), and 2010-2013 (after
      introducing the intervention), which was compared. To find out if teachers'
      reluctance to fail had decreased, qualitative feedback from the teachers was
      gathered and analysed. Since the implementation of the educational theme, the
      number of unprofessional behaviour judgments has risen. The teachers are positive
      about the implemented system of teaching and assessing professional behaviour,
      and feel less reluctant to award an unsatisfactory professional behaviour
      judgment. CONCLUSIONS: Supporting teachers in teaching and assessing professional
      behaviour and involving them in students' remediation appears to reduce their
      reluctance to fail students demonstrating unprofessional behaviour.

PMID- 24938393
TI  - CIRCUS: a package for Circos display of structural genome variations from paired
      end and mate-pair sequencing data.
AB  - BACKGROUND: Detection of large genomic rearrangements, such as large indels,
      duplications or translocations is now commonly achieved by next generation
      sequencing (NGS) approaches. Recently, several tools have been developed to
      analyze NGS data but the resulting files are difficult to interpret without an
      additional visualization step. Circos (Genome Res, 19:1639-1645, 2009), a Perl
      script, is a powerful visualization software that requires setting up numerous
      configuration files with a large number of parameters to handle. R packages like
      RCircos (BMC Bioinformatics, 14:244, 2013) or ggbio (Genome Biol, 13:R77, 2012)
      provide functions to display genomic data as circular Circos-like plots. However,
      these tools are very general and lack the functions needed to filter, format and
      adjust specific input genomic data. RESULTS: We implemented an R package called
      CIRCUS to analyze genomic structural variations. It generates both data and
      configuration files necessary for Circos, to produce graphs. Only few R pre
      requisites are necessary. Options are available to deal with heterogeneous data,
      various chromosome numbers and multi-scale analysis. CONCLUSION: CIRCUS allows
      fast and versatile analysis of genomic structural variants with Circos plots for
      users with limited coding skills.

PMID- 24938394
TI  - Cost of practice in a tertiary/quaternary referral center: is it sustainable?
AB  - BACKGROUND: Third-party payers are moving toward a bundled care payment system.
      This means that there will need to be a warranty cost of care-where the cost of
      complexity and complication rates is built into the bundled payment. The
      theoretical benefit of this system is that providers with lower complication
      rates will be able to provide care with lower warranty costs and lower overall
      costs. This may also result in referring riskier patients to tertiary or
      quaternary referral centers. Unless the payment model truly covers the higher
      cost of managing such referred cases, the economic risk may be unsustainable for
      these centers. METHODS: We took the last seven patients that were referred by
      other surgeons as "too high risk" for colectomy at other centers. A contribution
      margin was calculated using standard Medicare reimbursement rates at our
      institution and cost of care based on our administrative database. We then
      recalculated a contribution margin assuming a 3 % reduction in payment for a
      higher than average readmission rate, like that which will take effect in 2014.
      Finally, we took into account the cost of any readmissions. RESULTS: Seven
      patients with diagnosis related group (DRG) 330 were reviewed with an average age
      of 66.8 +/- 16 years, American Society of Anesthesiologists score 2.3 +/- 1.0,
      body mass index 31.6 +/- 9.8 kg/m(2) (range 22-51 kg/m(2)). There was a 57 %
      readmission rate, 29 % reoperation rate, 10.8 +/- 7.7 day average initial length
      of stay with 14 +/- 8.6 day average readmission length of stay. Forty-two percent
      were discharged to a location other than home. Seventy-one percent of these
      patients had Medicare insurance. The case mix index was 2.45. Average
      reimbursement for DRG 330 was $17,084 (based on Medicare data) for our facility
      in 2012, with the national average being $12,520. The total contribution margin
      among all cases collectively was -$19,122 +/- 13,285 (average per patient 
      $2,731, range -$21,905-$12,029). Assuming a 3 % reimbursement reduction made the
      overall contribution margin -$22,122 +/- 13,285 (average -$3,244). Including the
      cost of readmission in the variable cost made the contribution margin -$115,741
      +/- 16,023 (average -$16,534). CONCLUSIONS: Care of high-risk patients at
      tertiary and quaternary referral centers is a very expensive proposition and can
      lead to financial ruin under the current reimbursement system.

PMID- 24938395
TI  - Survivorship at minimum 10-year follow-up of a rotating-platform, mobile-bearing,
      posterior-stabilised total knee arthroplasty.
AB  - PURPOSE: To evaluate prospectively the long-term clinical and radiographic
      results and survivorship of a rotating-platform, posterior-stabilised knee
      prosthesis at minimum 10 years (mean 11.5 +/- 1.41 years), and to test the
      hypothesis that this design would have a mechanical survivorship greater than
      95%. METHODS: Between 2000 and 2002, 160 consecutive patients (166 knees)
      underwent total knee arthroplasty using a rotating-platform, posterior-stabilised
      prosthesis, and clinical and radiographic follow-up data were gathered
      prospectively. RESULTS: One hundred and seven patients (112 knees) were available
      for final follow-up. Five patients (3%) had undergone revision surgery, giving a
      Kaplan-Meier survival rate of 96.6% for all causes of failure. No spin-out of the
      polyethylene insert was observed. The mean visual analogue scale, Knee Society
      and Oxford Knee Scores showed statistically significant improvements (p < 0.001).
      On radiographs, two cases (2.4%) had radiolucent lines >2 mm, and no patient had
      osteolysis. CONCLUSIONS: The absence of osteolysis at minimum 10 years seems to
      support our hypothesis that this design may be able to reduce peri-prosthetic
      bone resorption in the long term. The survivorship was greater than 95% and is
      comparable to the best results reported for this type of knee prosthesis in the
      literature. The clinical scores are reasonable, given the presence of various
      disabling concomitant pathologies and the relatively advanced mean age of the
      study population. This study is clinically relevant because it adds valuable
      information to the limited data regarding the long-term survivorship and
      performance of rotating-platform knee prostheses and, more specifically, of a
      single knee design. LEVEL OF EVIDENCE: IV.

PMID- 24938397
TI  - Pseudo painting/air bubble technique for planar lipid bilayers.
AB  - BACKGROUND: A functional reconstitution of channel proteins in planar lipid
      bilayers is still very versatile to study structure/function correlates under
      well-defined conditions at the single protein level. NEW METHOD: In this study we
      present an improved planar lipid bilayer technique in which an air bubble is used
      for stabilizing unstable/leaky bilayers or for removing excess lipids. The bubble
      can also be used as a tool for reducing the number of channels in the bilayer
      with the goal of having only one active channel in the membrane. RESULTS: Stable
      planar lipid bilayers are formed within seconds to minutes. In the case of
      multiple channel insertion the air bubble can be used to reduce the number of
      channels within minutes. COMPARISON WITH EXISTING METHOD(S): The simple
      improvement of the classical folding technique guarantees a very fast creation of
      stable bilayers even with difficult phospholipids in a conventional vertical
      bilayer set-up; it requires no modifications of the existing set-up. CONCLUSIONS:
      This technique is very easy to handle and guarantees successful single channel
      recordings for any kind of planar lipid bilayer experiment.

PMID- 24938396
TI  - Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in
      elite athletes: a randomized control trial.
AB  - PURPOSE: Syndesmotic sprains are uncommon injuries that require prolonged
      recovery. The influence of ultrasound-guided injections of platelet-rich plasma
      (PRP) into the injured antero-inferior tibio-fibular ligaments (AITFL) in
      athletes on return to play (RTP) and dynamic stability was studied. METHODS:
      Sixteen elite athletes with AITFL tears were randomized to a treatment group
      receiving injections of PRP or to a control group. All patients followed an
      identical rehabilitation protocol and RTP criteria. Patients were prospectively
      evaluated for clinical ability to return to full activity and residual pain.
      Dynamic ultrasound examinations were performed at initial examination and at 6
      weeks post-injury to demonstrate re-stabilization of the syndesmosis joint and
      correlation with subjective outcome. RESULTS: All patients presented with a tear
      to the AITFL with dynamic syndesmosis instability in dorsiflexion-external
      rotation, and larger neutral tibia-fibula distance on ultrasound. Early diagnosis
      and treatment lead to shorter RTP, with 40.8 (+/-8.9) and 59.6 (+/-12.0) days for
      the PRP and control groups, respectively (p = 0.006). Significantly less residual
      pain upon return to activity was found in the PRP group; five patients (62.5 %)
      in the control group returned to play with minor discomfort versus one patient in
      the treatment group (12.5 %). One patient in the control group had continuous
      pain and disability and subsequently underwent syndesmosis reconstruction.
      CONCLUSIONS: Athletes suffering from high ankle sprains benefit from ultrasound
      guided PRP injections with a shorter RTP, re-stabilization of the syndesmosis
      joint and less long-term residual pain. LEVEL OF EVIDENCE: II.

PMID- 24938398
TI  - [Noninvasive ventilation in patients with persistent hypercapnia].
AB  - BACKGROUND: Chronic respiratory failure is caused by insufficiency of the
      inspiratory muscles, i.e. mainly the diaphragm, which represents the so-called
      "respiratory pump". Insufficiency of the respiratory pump causes hypercapnia.
      THERAPEUTIC INTERVENTION: Diseases with chronic hypercapnia are characterized by
      reduced survival. Mechanical ventilation-mostly applied as noninvasive mechanical
      ventilation (NIV)-improves ventilation and unloads the inspiratory muscles.
      INDICATION: Strong evidence supports the use of domiciliary NIV already in mild
      degrees of chronic respiratory failure caused by neuromuscular diseases, thoracic
      restrictions and obesity hypoventilation. In these diseases long-term NIV
      improves both physiological parameters (such as blood gases) and clinical
      outcome, e.g. exercise capacity, right heart dysfunction, sleep quality, disease
      specific aspects of health-related quality of life (HRQL) and survival rate. In
      contrast, its influence on long-term survival in chronic obstructive pulmonary
      disease (COPD) patients is not clearly proven. Prescription of home NIV in COPD
      should therefore be restricted to severe degrees of chronic respiratory failure.
      Finally, there is an indication for domiciliary NIV in patients after prolonged
      weaning from mechanical ventilation. This paper elaborates underlying
      pathophysiology, diseases and how NIV works in chronic hypercapnic respiratory
      failure.

PMID- 24938399
TI  - 3-Nitropropionic acid-induced ischemia tolerance in the rat brain is mediated by
      reduced metabolic activity and cerebral blood flow.
AB  - Tissue tolerance to ischemia can be achieved by noxious stimuli that are below a
      threshold to cause irreversible damage ('preconditioning'). Understanding the
      mechanisms underlying preconditioning may lead to the identification of novel
      therapeutic targets for diseases such as stroke. We here used the oxidative chain
      inhibitor 3-nitropropionic acid (NPA) to induce ischemia tolerance in a rat
      middle cerebral artery occlusion (MCAO) stroke model. Cerebral blood flow (CBF)
      and structural integrity were characterized by longitudinal magnetic resonance
      imaging (MRI) in combination with behavioral, histologic, and biochemical
      assessment of NPA-preconditioned animals and controls. Using this approach we
      show that the ischemia-tolerant state is characterized by a lower energy charge
      potential and lower CBF, indicating a reduced baseline metabolic demand, and
      therefore a cellular mechanism of neural protection. Blood vessel density and
      structural integrity were not altered by NPA treatment. When subjected to MCAO,
      preconditioned animals had a characteristic MRI signature consisting of enhanced
      CBF maintenance within the ischemic territory and intraischemic reversal of the
      initial cytotoxic edema, resulting in reduced infarct volumes. Thus, our data
      show that tissue protection through preconditioning occurs early during ischemia
      and indicate that a reduced cellular metabolism is associated with tissue
      tolerance to ischemia. 

PMID- 24938400
TI  - Role of Akt and mammalian target of rapamycin in functional outcome after
      concussive brain injury in mice.
AB  - Akt (protein kinase B) and mammalian target of rapamycin (mTOR) have been
      implicated in the pathogenesis of cell death and cognitive outcome after cerebral
      contusion in mice; however, a role for Akt/mTOR in concussive brain injury has
      not been well characterized. In a mouse closed head injury (CHI) concussion
      traumatic brain injury (TBI) model, phosphorylation of Akt (p-Akt), mTOR (p
      mTOR), and S6RP (p-S6RP) was increased by 24 hours in cortical and hippocampal
      brain homogenates (P<0.05 versus sham for each), and p-S6RP was robustly induced
      in IBA-1+ microglia and glial fibrillary acidic protein-positive (GFAP+)
      astrocytes. Pretreatment with inhibitors of Akt or mTOR individually by the
      intracerebroventricular route reduced phosphorylation of their respective direct
      substrates FOXO1 (P<0.05) or S6RP (P<0.05) after CHI, confirming the activity of
      inhibitors. Rapamycin pretreatment significantly worsened hidden platform
      (P<0.01) and probe trial (P<0.05) performance in CHI mice.
      Intracerebroventricular administration of necrostatin-1 (Nec-1) before CHI
      increased hippocampal Akt and S6RP phosphorylation and improved place learning
      (probe trials, P<0.001 versus vehicle), whereas co-administration of rapamycin or
      Akt inhibitor with Nec-1 eliminated improved probe trial performance. These data
      suggest a beneficial role for Akt/mTOR signaling after concussion TBI independent
      of cell death that may contribute to improved outcome by Nec-1. 

PMID- 24938401
TI  - Reliable estimation of capillary transit time distributions using DSC-MRI.
AB  - The regional availability of oxygen in brain tissue is traditionally inferred
      from the magnitude of cerebral blood flow (CBF) and the concentration of oxygen
      in arterial blood. Measurements of CBF are therefore widely used in the
      localization of neuronal response to stimulation and in the evaluation of
      patients suspected of acute ischemic stroke or flow-limiting carotid stenosis. It
      was recently demonstrated that capillary transit time heterogeneity (CTH) limits
      maximum oxygen extraction fraction (OEF(max)) that can be achieved for a given
      CBF. Here we present a statistical approach for determining CTH, mean transit
      time (MTT), and CBF using dynamic susceptibility contrast magnetic resonance
      imaging (DSC-MRI). Using numerical simulations, we demonstrate that CTH, MTT, and
      OEF(max) can be estimated with low bias and variance across a wide range of
      microvascular flow patterns, even at modest signal-to-noise ratios. Mean transit
      time estimated by singular value decomposition (SVD) deconvolution, however, is
      confounded by CTH. The proposed technique readily identifies malperfused tissue
      in acute stroke patients and appears to highlight information not detected by the
      standard SVD technique. We speculate that this technique permits the non-invasive
      detection of tissue with impaired oxygen delivery in neurologic disorders such as
      acute ischemic stroke and Alzheimer's disease during routine diagnostic imaging. 

PMID- 24938402
TI  - Impaired brain energy metabolism in the BACHD mouse model of Huntington's
      disease: critical role of astrocyte-neuron interactions.
AB  - Huntington's disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat
      expansions in the huntingtin (Htt) gene. Although early energy metabolic
      alterations in HD are likely to contribute to later neurodegenerative processes,
      the cellular and molecular mechanisms responsible for these metabolic alterations
      are not well characterized. Using the BACHD mice that express the full-length
      mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated
      localized in vivo changes in brain glucose use reminiscent of what is observed in
      premanifest HD carriers. Using biochemical, molecular, and functional analyses on
      different primary cell culture models from BACHD mice, we observed that mHtt does
      not directly affect metabolic activity in a cell autonomous manner. However,
      coculture of neurons with astrocytes from wild-type or BACHD mice identified
      mutant astrocytes as a source of adverse non-cell autonomous effects on neuron
      energy metabolism possibly by increasing oxidative stress. These results suggest
      that astrocyte-to-neuron signaling is involved in early energy metabolic
      alterations in HD. 

PMID- 24938403
TI  - Endovascular perforation subarachnoid hemorrhage fails to cause Morris water maze
      deficits in the mouse.
AB  - Cognitive dysfunction is the primary driver of poor long-term outcome in
      aneurysmal subarachnoid hemorrhage (SAH) survivors; modeling such deficits
      preclinically is thus key for mechanistic and translational investigation.
      Although rat SAH causes long-term deficits in learning and memory, it remains
      unknown whether similar deficits are seen in the mouse, a species particularly
      amenable to powerful, targeted genetic manipulation. We thus subjected mice to
      endovascular perforation SAH and assessed long-term cognitive outcome via the
      Morris water maze (MWM), the most commonly used metric for rodent neurocognition.
      No significant differences in MWM performance (by either of two protocols) were
      seen in SAH versus sham mice. Moreover, SAH caused negligible hippocampal CA1
      injury. These results undercut the potential of commonly used methods (of SAH
      induction and assessment of long-term neurocognitive outcome) for use in targeted
      molecular studies of SAH-induced cognitive deficits in the mouse. 

PMID- 24938406
TI  - Clinical Raman measurements under special ambient lighting illumination.
AB  - One challenge in facing the application of biomedical Raman spectroscopy is that
      the Raman signal is acquired in a dark operation room. It is inconvenient for
      both the operator and the patient because it is difficult for the operator to
      accurately and precisely locate the target in the dark environment, and the
      patient feels uncomfortable in such a setting. In this note, we propose a method
      to implement biomedical Raman measurement with an illumination source, by
      multiple filtering of the illumination and the collection optics. Experimental
      results are demonstrated on skin Raman measurement under 785-nm excitation.

PMID- 24938404
TI  - Circadian and homeostatic modulation of functional connectivity and regional
      cerebral blood flow in humans under normal entrained conditions.
AB  - Diurnal rhythms have been observed in human behaviors as diverse as sleep,
      olfaction, and learning. Despite its potential impact, time of day is rarely
      considered when brain responses are studied by neuroimaging techniques. To
      address this issue, we explicitly examined the effects of circadian and
      homeostatic regulation on functional connectivity (FC) and regional cerebral
      blood flow (rCBF) in healthy human volunteers, using whole-brain resting-state
      functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL).
      In common with many circadian studies, we collected salivary cortisol to
      represent the normal circadian activity and functioning of the hypothalamic
      pituitary-adrenal (HPA) axis. Intriguingly, the changes in FC and rCBF we
      observed indicated fundamental decreases in the functional integration of the
      default mode network (DMN) moving from morning to afternoon. Within the anterior
      cingulate cortex (ACC), our results indicate that morning cortisol levels are
      negatively correlated with rCBF. We hypothesize that the homeostatic mechanisms
      of the HPA axis has a role in modulating the functional integrity of the DMN
      (specifically, the ACC), and for the purposes of using fMRI as a tool to measure
      changes in disease processes or in response to treatment, we demonstrate that
      time of the day is important when interpreting resting-state data. 

PMID- 24938405
TI  - Quality of cardiovascular disease care in Ontario's primary care practices: a
      cross sectional study examining differences in guideline adherence by patient
      sex.
AB  - BACKGROUND: Women are disproportionately affected by cardiovascular disease,
      often experiencing poorer outcomes following a cardiovascular event. Evidence
      points to inequities in processes of care as a potential contributing factor.
      This study sought to determine whether any sex differences exist in adherence to
      process of care guidelines for cardiovascular disease within primary care
      practices in Ontario, Canada. METHODS: This is a secondary analysis of pooled
      cross-sectional baseline data collected through a larger quality improvement
      initiative known as the Improved Delivery of Cardiovascular Care (IDOCC). Chart
      abstraction was performed for 4,931 patients from 84 primary care practices in
      Eastern Ontario who had, or were at high risk of, cardiovascular disease.
      Measures examining adherence to guidelines associated with nine areas of
      cardiovascular care (coronary artery disease, peripheral vascular disease (PVD),
      stroke/transient ischemic attack, chronic kidney disease, diabetes, dyslipidemia,
      hypertension, smoking cessation, and weight management) were collected.
      Multivariable logistic regression analysis was performed to evaluate sex
      differences, adjusting for age, physician remuneration, and rurality. RESULTS:
      Women were significantly less likely to have their lipid profiles taken (OR=1.17,
      95% CI 1.03-1.33), be prescribed lipid lowering medication for dyslipidemia
      (OR=1.54, 95% CI 1.20-1.97), and to be prescribed ASA following stroke (OR=1.56,
      95% CI 1.39-1.75). Women with PVD were significantly less likely to be prescribed
      ACE inhibitors and/or angiotensin receptor blockers (OR=1.74, 95% CI 1.25-2.41)
      and lipid lowering medications (OR=1.95, 95% CI 1.46-2.62) or ASA (OR=1.59, 95%
      CI 1.43-1.78). However, women were more likely to have two blood pressure
      measurements taken and to be referred to a dietician or weight loss program. Male
      patients with diabetes were less likely to be prescribed glycemic control
      medication (OR=0.84, 95% CI 0.74-0.86). CONCLUSIONS: Sex disparities exist in the
      quality of cardiovascular care in Canadian primary care practices, which tend to
      favour men. Women with PVD have a particularly high risk of not receiving
      appropriate medications. Our findings indicate that improvements in care delivery
      should be made to address these issues, particularly with regard to the
      prescribing of recommended medications for women, and preventive measures for
      men.

PMID- 24938407
TI  - MED12 overexpression is a frequent event in castration-resistant prostate cancer.
AB  - In a recent effort to unravel the molecular basis of prostate cancer (PCa),
      Barbieri and colleagues using whole-exome sequencing identified a novel
      recurrently mutated gene, MED12, in 5.4% of primary PCa. MED12, encoding a
      subunit of the Mediator complex, is a transducer of Wnt/beta-catenin signaling,
      linked to modulation of hedgehog signaling and to the regulation of transforming
      growth factor beta (TGFbeta)-receptor signaling. Therefore, these studies
      prompted us to investigate the relevance of MED12 in PCa. Expression of MED12,
      SMAD3 phosphorylation, and proliferation markers was assessed by
      immunohistochemistry on tissue microarrays from 633 patients. siRNA-mediated
      knockdown of MED12 was carried out on PCa cell lines followed by cellular
      proliferation assays, cell cycle analysis, apoptosis assays, and treatments with
      recombinant TGFbeta3. We found nuclear overexpression of MED12 in 40% (28/70) of
      distant metastatic castration-resistant prostate cancer (CRPC(MET)) and 21%
      (19/90) of local-recurrent CRPC (CRPC(LOC)) in comparison with frequencies of
      less than 11% in androgen-sensitive PCa, and no overexpression in benign
      prostatic tissues. MED12 expression was significantly correlated with high
      proliferative activity in PCa tissues, whereas knockdown of MED12 decreased
      proliferation, reduced G1- to S-phase transition, and increased the expression of
      the cell cycle inhibitor p27. TGFbeta signaling activation associates with MED12
      nuclear overexpression in tissues and results in a strong increase in MED12
      nuclear expression in cell lines. Furthermore, MED12 knockdown reduced the
      expression of the TGFbeta target gene vimentin. Our findings show that MED12
      nuclear overexpression is a frequent event in CRPC in comparison with androgen
      sensitive PCa and is directly implicated in TGFbeta signaling.

PMID- 24938408
TI  - Deficiency of ERbeta and prostate tumorigenesis in FGF8b transgenic mice.
AB  - Estrogens contribute to the development and growth of the prostate and are
      implicated in prostate tumorigenesis. In their target tissues, estrogens mediate
      their effects via estrogen receptor alpha (ERalpha (ESR1)) and beta (ERbeta
      (ESR2)). Hyperplasia and decreased differentiation of epithelial cells in the
      prostate have been reported in ERbeta knockout (BERKO) mice. Herein, we studied
      the effect of ERbeta deficiency on prostate tumorigenesis by crossing BERKOFVB
      mice with prostate-targeted human fibroblast growth factor 8b transgenic (FGF8b
      Tg) mice. Consistent with results described in our previous report, the prostates
      of 1-year-old FGF8b-Tg mice displayed stromal aberrations, prostatic
      intraepithelial neoplasia (mPIN) lesions, inflammation, and occasionally cancer.
      The prostates of BERKOFVB mice exhibited mild epithelial hypercellularity and
      inflammation. The prostate phenotypes of FGF8b-Tg-BERKOFVB mice closely resembled
      those of FGF8b-Tg mice. However, mucinous metaplasia, indicated by Goblet-like
      cells in the epithelium, was significantly more frequent in the prostates of
      FGF8b-Tg-BERKOFVB mice when compared with FGF8b-Tg mice. Furthermore, compared
      with FGF8b-Tg mice, there was a tendency for increased frequency of inflammation
      but milder hyperplasias in the prostate stroma of FGF8b-Tg-BERKOFVB mice. The
      expression levels of mRNAs for FGF8b-regulated genes including osteopontin
      (Spp1), connective tissue growth factor (Ctgf), fibroblast growth factor
      receptors (Fgfrs), and steroid hormone receptors and cytokines were similar in
      the prostates of FGF8b-Tg and FGF8b-Tg-BERKOFVB mice. Our results indicate that
      ERbeta plays a role in the differentiation of the prostatic epithelium and,
      potentially, in the defensive mechanism required for protection against
      inflammation but do not support a direct tumor-suppressive function of ERbeta in
      the prostate of FGF8b-Tg mice.

PMID- 24938410
TI  - Chemical speciation of heavy metals by surface-enhanced Raman scattering
      spectroscopy: identification and quantification of inorganic- and methyl-mercury
      in water.
AB  - Chemical speciation of heavy metals has become extremely important in
      environmental and analytical research because of the strong dependence that
      toxicity, environmental mobility, persistence and bioavailability of these
      pollutants have on their specific chemical forms. Novel nano-optical-based
      detection strategies, capable of overcoming the intrinsic limitations of well
      established analytic methods for the quantification of total metal ion content,
      have been reported, but the speciation of different chemical forms has not yet
      been achieved. Here, we report the first example of a SERS-based sensor for
      chemical speciation of toxic metal ions in water at trace levels. Specifically,
      the inorganic Hg(2+) and the more toxicologically relevant methylmercury
      (CH3Hg(+)) are selected as analytical targets. The sensing platform consists of a
      self-assembled monolayer of 4-mercaptopyridine (MPY) on highly SERS-active and
      robust hybrid plasmonic materials formed by a dense layer of interacting gold
      nanoparticles anchored onto polystyrene microbeads. The co-ordination of Hg(2+)
      and CH3Hg(+) to the nitrogen atom of the MPY ring yields characteristic changes
      in the vibrational SERS spectra of the organic chemoreceptor that can be
      qualitatively and quantitatively correlated to the presence of the two different
      mercury forms.

PMID- 24938409
TI  - Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes
      yet distinct mechanisms.
AB  - Ciliopathies are genetic disorders that are caused by dysfunctional cilia and
      affect multiple organs. One type of ciliopathy, Bardet-Biedl syndrome, is a rare
      disorder characterized by obesity, retinitis pigmentosa, polydactyly, mental
      retardation and susceptibility to cardiovascular diseases. The Wnt/Planar cell
      polarity (PCP) has been associated with cilia function and ciliogenesis in
      directing the orientation of cilia and basal bodies. Yet the exact relationship
      between PCP and ciliopathy is not well understood. Here, we examine interactions
      between a core PCP component, Prickle2 (Pk2), and a central BBS gene, Bbs7, using
      gene knockdown in the zebrafish. pk2 and bbs7 knockdown both disrupt the
      formation of a ciliated organ, the Kupffer's vesicle (KV), but do not display a
      synergistic interaction. By measuring cell polarity in the neural tube, we find
      that bbs7 activity is not required for Pk asymmetric localization. Moreover, BBS
      protein complex formation is preserved in the Pk2-deficient (Pk2(-/-)) mouse.
      Previously we reported an intracellular melanosome transport delay as a cardinal
      feature of reduced bbs gene activity. We find that pk2 knockdown suppresses bbs7
      related retrograde transport delay. Similarly, knockdown of ift22, an anterograde
      intraflagellar transport component, also suppresses the bbs7-related retrograde
      delay. Notably, we find that pk2 knockdown larvae show a delay in anterograde
      transport. These data suggest a novel role for Pk2 in directional intracellular
      transport and our analyses show that PCP and BBS function independently, yet
      result in overlapping phenotypes when knocked down in zebrafish. 

PMID- 24938411
TI  - Ullrich congenital muscular dystrophy: clinicopathological features, natural
      history and pathomechanism(s).
AB  - Collagen VI is widely distributed throughout extracellular matrices (ECMs) in
      various tissues. In skeletal muscle, collagen VI is particularly concentrated in
      and adjacent to basement membranes of myofibers. Ullrich congenital muscular
      dystrophy (UCMD) is caused by mutations in either COL6A1, COL6A2 or COL6A3 gene,
      thereby leading to collagen VI deficiency in the ECM. It is known to occur
      through either recessive or dominant genetic mechanism, the latter most typically
      by de novo mutations. UCMD is well defined by the clinicopathological hallmarks
      including distal hyperlaxity, proximal joint contractures, protruding calcanei,
      scoliosis and respiratory insufficiency. Recent reports have depicted the robust
      natural history of UCMD; that is, loss of ambulation by early teenage years,
      rapid decline in respiratory function by 10 years of age and early-onset, rapidly
      progressive scoliosis. Muscle pathology is characterised by prominent
      interstitial fibrosis disproportionate to the relative paucity of necrotic and
      regenerating fibres. To date, treatment for patients is supportive for symptoms
      such as joint contractures, respiratory failure and scoliosis. There have been
      clinical trials based on the theory of mitochondrion-mediated myofiber apoptosis
      or impaired autophagy. Furthermore, the fact that collagen VI producing cells in
      skeletal muscle are interstitial mesenchymal cells can support proof of concept
      for stem cell-based therapy. 

PMID- 24938412
TI  - [Diabetic nephropathy: emerging treatments].
AB  - Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The
      mainstay of treatment has been management of hyperglycaemia, blood pressure and
      proteinuria using hypoglycemic agents, ACE inhibitors, and angiotensin receptor
      blockers. Since 2000, new therapeutic strategies began to emerge targeting the
      biochemical activity of glucose molecules on the renal tissue. Various substances
      have been studied with varying degrees of success, ranging from vitamin B to
      camel's milk. Silymarin reduces urinary excretion of albumin, tumor necrosis
      factor (TNF)-alpha, and malondialdehyde in patients with diabetic nephropathy and
      may be considered as a novel addition to the anti-diabetic nephropathy
      armamentarium. Although some results are promising, studies on a larger scale are
      needed to validate the utility of these molecules in the treatment of the DN. 

PMID- 24938414
TI  - Mitochondrial tRNA mutations manifest not only as hypertrophic cardiomyopathy but
      also as noncompaction--reply.

PMID- 24938413
TI  - Small molecules that target the toxic RNA in myotonic dystrophy type 2.
AB  - Myotonic dystrophy type 2 (DM2) is caused by an expansion of CCTG repeats in the
      zinc-finger protein gene (ZNF9). Transcribed CCUG repeats sequester muscleblind
      like protein 1 (MBNL1), an important alternative splicing regulator, preventing
      its normal function, leading to the disease phenotype. We describe a series of
      ligands that disrupt the MBNL1-r(CCUG)n interaction as potential lead agents for
      developing DM2 therapeutics. A previously reported triaminopyrimidine-acridine
      conjugate was a moderate inhibitor in vitro, however it proved to be poorly water
      soluble and not cell-permeable. To improve its therapeutic potential, the new set
      of ligands maintained the key triaminopyrimidine recognition unit but replaced
      the acridine intercalator with a bisamidinium groove binder. The optimized
      ligands exhibit low micromolar inhibition potency to MBNL1-r(CCUG)8. Importantly,
      the ligands are the first to show the ability to disrupt the MBNL1-r(CCUG)n foci
      in DM2 model cell culture and exhibit low cytotoxicity.

PMID- 24938415
TI  - Mitochondrial tRNA mutations manifest not only as hypertrophic cardiomyopathy but
      also as noncompaction.

PMID- 24938417
TI  - Selective versus comprehensive neck dissection in the treatment of patients with
      a pathologically node-positive neck with or without microscopic extracapsular
      spread in oral squamous cell carcinoma.
AB  - The objective of this study was to compare the prognosis and complications
      between selective neck dissection (SND) and comprehensive neck dissection (CND)
      for patients with a pathologically node-positive neck in squamous cell carcinoma
      of the tongue and the floor of the mouth. This was a retrospective cohort study.
      There was no significant difference between the SND group and the CND group in 3
      year neck control rate (86.2% vs. 85.9%, P=0.797) or disease-specific survival
      (DSS) rate (64.6% vs. 61.9%, P=0.646). Further analyses of the respective 3-year
      DSS rates in the SND and CND subgroups were as follows: pN1 without extracapsular
      spread (ECS), 67.7% vs. 72.2%, P=0.851; pN2b without ECS, 64.7% vs. 68.8%,
      P=0.797; and pN+ with ECS, 57.1% vs. 60.0%, P=0.939. Of note, there were
      significantly fewer complications in the SND group compared with the CND group
      (7.3% vs. 20.0%, P=0.032). Multivariate analysis showed that the modality of neck
      treatment, pN+ status, and microscopic ECS did not serve as independent
      prognostic factors. SND plus adjuvant radiotherapy is a management strategy of
      high efficiency and minor morbidity for selected oral cancer patients with a pN+
      neck with or without microscopic ECS.

PMID- 24938416
TI  - Insights into battles between Mycobacterium tuberculosis and macrophages.
AB  - As the first line of immune defense for Mycobacterium tuberculosis (Mtb),
      macrophages also provide a major habitat for Mtb to reside in the host for years.
      The battles between Mtb and macrophages have been constant since ancient times.
      Triggered upon Mtb infection, multiple cellular pathways in macrophages are
      activated to initiate a tailored immune response toward the invading pathogen and
      regulate the cellular fates of the host as well. Toll-like receptors (TLRs)
      expressed on macrophages can recognize pathogen-associated-molecular patterns
      (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as
      tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D
      receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected
      macrophages, by which Vitamin D participates in innate immune responses. The
      signaling pathways that involve TNF, type I IFNs and Vitamin D are inter
      connected, which play critical roles in the regulation of necroptosis, apoptosis,
      and autophagy of the infected macrophages. This review article summarizes current
      knowledge about the interactions between Mtb and macrophages, focusing on
      cellular fates of the Mtb-infected macrophages and the regulatory molecules and
      cellular pathways involved in those processes. 

PMID- 24938418
TI  - Very short NMR relaxation times of anions in ionic liquids: new pulse sequence to
      eliminate the acoustic ringing.
AB  - NMR relaxation processes of anions were studied in two neat imidazolium-based
      room temperature ionic liquids (RTILs) 1-decyl-3-methyl-imidazolium bromide- and
      chloride. The spin-lattice and spin-spin relaxations of 81Br and 35Cl nuclei were
      found to be extremely fast due to very strong quadrupolar interactions. The
      determined relaxation rates are comparable with those observed in the solids or
      in some critical organic solute/water/salt systems. In order to eliminate the
      acoustic ringing of the probe-head during relaxation times measurements the novel
      pulse sequence has been devised. It is based on the conventional inversion
      recovery pulse sequence, however, instead of the last 90 degrees  pulse the
      subsequence of three 90 degrees  pulses applied along axes to fulfill the phase
      cycling condition is used. Using this pulse sequence it was possible to measure
      T1 for both studied nuclei. The viscosity measurements have been carried out and
      the rotational correlation times were calculated. The effective 35Cl quadrupolar
      coupling constant was found to be almost one order lower than that for 81Br, i.e.
      1.8 MHz and 16.0 MHz, respectively. Taking into account the facts that the ratio
      of (Q(35Cl)/Q(81Br))2~0.1 and EFG tensors on the anions are quite similar,
      analogous structural organizations are expected for both RTILs. The observed
      T1/T2 (1.27-1.44) ratios were found to be not sufficiently high to confirm the
      presence of long-living (on the time scale of >=10(-8) s) mesoscopic structures
      or heterogeneities in the studied neat ionic liquids.

PMID- 24938419
TI  - Accuracy and reliability of linear measurements using 3-dimensional computed
      tomographic imaging software for Le Fort I osteotomy.

PMID- 24938420
TI  - Triazine-based mesoporous covalent imine polymers as solid supports for copper
      mediated Chan-Lam cross-coupling N-arylation reactions.
AB  - The synthesis of a novel mesoporous covalent imine polymeric (MCIPs) material,
      involving simple Schiff-base chemistry, is reported. This highly functionalised
      nitrogen-rich material acts as a good support for immobilising Cu(II) ions,
      exhibiting excellent catalytic activity in promoting the Chan-Lam cross-coupling
      reaction between biologically active amines and arylboronic acids. The
      performance of this catalyst is also evident from its broad substrate scope, high
      stability, real heterogeneity, mild reaction conditions and reusability without
      loss of activity. The observed results will provide additional scope on the
      design and catalytic applications of this emerging class of materials. 

PMID- 24938421
TI  - Comparison between in situ and ex situ gamma measurements on land areas within a
      decommissioning nuclear site: a case study at Dounreay.
AB  - Measurements made in situ with gamma detectors and ex situ measurements of soil
      samples in a laboratory can have complementary roles in the assessment of
      radioactively contaminated land on decommissioning nuclear sites. Both in situ
      and ex situ methods were used to characterize (137)Cs contamination within an
      area at the Dounreay site in Scotland. The systematic difference (bias) between
      estimates of the mean activity concentration was found to be non-significant when
      in situ measurements were interpreted using a linear depth model, based on ex
      situ measurements made at two different depths. An established method of
      evaluating the random components of measurement uncertainty was used. The random
      component of analytical uncertainty in the in situ measurements, made in field
      conditions, was found to exceed that for the ex situ measurements, made in the
      controlled conditions of a laboratory. However, contamination by the target
      radionuclide was found to be heterogeneous over small spatial scales. This
      resulted in significantly higher levels of random sampling uncertainty in
      individual ex situ measurements. As in situ measurements are substantially less
      costly, a greater number of measurements can be made, which potentially reduces
      the uncertainty on the mean. Providing the depth profile of contaminants can be
      modelled with confidence, this can enable estimates of mean activity
      concentration over an averaging area to be made with lower overall uncertainties
      than are possible using ex situ methods. 

PMID- 24938422
TI  - Effects of obstetric complications on volume and functional connectivity of
      striatum in anorexia nervosa patients.
AB  - OBJECTIVE: To investigate the volume and functional connectivity of dorsal and
      ventral striatal nuclei in anorexia nervosa (AN) and their relationship with
      early exposure to obstetric complications. METHOD: Fifty-one patients with
      lifetime AN (35 acute, 16 recovered) and 34 healthy controls underwent high
      resolution and resting-state functional magnetic resonance imaging. RESULTS: The
      AN group showed reduced functional connectivity of the putamen compared with
      healthy women, and this reduction was more evident in patients with lifetime
      binge eating/purging. Both acute and recovered AN groups showed a larger left
      accumbens area compared with that of healthy women. The functional connectivity
      of bilateral nucleus accumbens and putamen showed significant negative
      correlations with number of obstetric complications in the AN group. DISCUSSION:
      This study supports the hypothesis that AN is associated with structural and
      functional alterations of striatal networks, and reveals the possible role of
      obstetric complications in the pathogenesis of striatal dysfunction.

PMID- 24938423
TI  - Universal health coverage may not be enough to ensure universal access to sexual
      and reproductive health beyond 2014.
AB  - With the expiration of the Millennium Development Goals looming at the end of
      2015, governments have set themselves the task of defining a new set of
      sustainable development goals for the years beyond. This debate has major
      implications for how global public health will be addressed moving forward -
      particularly sexual and reproductive health and rights, which are the centrepiece
      of the International Conference on Population and Development agenda. One idea
      that has generated significant attention is universal health coverage. Universal
      health coverage is one, among many tools, that can help to address the sexual and
      reproductive health needs of women, adolescents and other marginalised groups
      such as migrants, people with disabilities, people of diverse sexual orientations
      and gender identities, sex workers and people who use drugs. However, a singular
      focus on universal health coverage is not likely to be sufficient to meet these
      needs; in fact, recent experiences have demonstrated that it often falls short.
      Without addressing the full range of factors that affect health, including social
      determinants of health, we will not be able to achieve the development goals of
      ensuring universal access to sexual and reproductive health or reducing
      preventable related mortalities and morbidities. 

PMID- 24938424
TI  - The feasibility and benefits of a 12-week yoga intervention for pediatric cancer
      out-patients.
AB  - BACKGROUND: Increasing rates of survival present a new set of psychosocial and
      physical challenges for children undergoing treatment for cancer. Physical
      activity (PA) has been shown to be a safe and effective strategy to mitigate the
      significant burden of cancer and its treatments, with yoga increasingly gaining
      recognition as a gentle alternative. The purpose of this study was to determine
      the feasibility and benefits of a 12-week community-based yoga intervention on
      health-related quality of life (HRQL), select physical fitness outcomes and PA
      levels (PAL). PROCEDURE: Eight pediatric cancer out-patients (4 male; 4 female;
      Mage  = 11.88, SD = 4.26) participated in the 12-week intervention consisting of
      supervised yoga sessions 2 times/week. Participants (patients and parent proxies)
      completed measures assessing HRQL, physical fitness and PAL at baseline and post
      intervention. RESULTS: Rates of recruitment, retention, attendance and adverse
      events indicated the program was feasible. Wilcoxon Signed Rank tests indicated
      significant improvements for patient (P = 0.02) and parent reported HRQL (P =
      0.03), functional mobility (P = 0.01), hamstring flexibility (left, P = 0.01 and
      right P = 0.02), and total PAL (P = 0.02) pre to post intervention. CONCLUSION:
      This 12-week community-based yoga intervention was feasible and provides
      preliminary evidence for the benefits of yoga on HRQL, physical fitness and PAL
      in pediatric cancer out-patients. In a population where sedentary behavior and
      the associated co-morbidities are a growing concern, these results promote the
      continued exploration of yoga programming.

PMID- 24938426
TI  - Highly chemo-, enantio-, and regioselective synthesis of alpha,alpha
      disubstituted furanones by Cu-catalyzed conjugate addition.
AB  - A highly chemo-, enantio-, and regioselective synthesis of furanones bearing an
      alpha,alpha-disubstituted quaternary stereogenic center is reported. The Cu
      catalyzed enantioselective conjugate addition of organoaluminum reagents to
      unsaturated ketoesters at room temperature and subsequent lactonization took
      place. Synthetic transformations of furanones represent facile approaches to
      various cyclic or acyclic compounds bearing a quaternary stereogenic center. 

PMID- 24938425
TI  - Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child
      development and behaviour.
AB  - BACKGROUND: Animal studies have linked in utero vitamin D exposure to various
      aspects of offspring brain development. Limited research has translated these
      findings to humans, and none have employed cord blood to measure exposure late in
      gestation. METHODS: Our objective was to examine the associations between
      maternal 25(OH)D measured at <=26 weeks' gestation or cord blood 25(OH)D and
      offspring global development, IQ, achievement, and behaviour in the US
      Collaborative Perinatal Project (1959-73). This was a secondary analysis of data
      from a case-cohort study, with 3896 women and children who participated in at
      least one outcome assessment. Psychologists assessed global development at 8
      months, IQ and behaviour at 4 and 7 years, and achievement at 7 years. Multiple
      linear and logistic regression was used to examine the associations between
      25(OH)D and child outcomes, controlling for maternal education, age, parity,
      race, maternal body mass index, marital status, smoking, gestational age and
      month of blood draw, and study site. RESULTS: Positive associations for many
      outcomes were greatly attenuated upon adjustment for confounders and were
      generally null. Only IQ at age 7 was associated with both maternal and cord blood
      25(OH)D, but the effect estimates were very small (beta for 5 nmol/L increment of
      maternal 25(OH)D = 0.10; [95% CI 0.00, 0.19]). CONCLUSION: We observed very
      little indication that maternal or cord blood 25(OH)D are associated with
      cognitive development, achievement, and behaviour between 8 months and 7 years of
      age.

PMID- 24938427
TI  - Integrative genomic analyses of secreted protein acidic and rich in cysteine and
      its role in cancer prediction.
AB  - Secreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or
      basement-membrane-40 (BM-40), is a matrix-associated protein that elicits changes
      in cell shape, inhibits cell-cycle progression and affects the synthesis of
      extracellular matrix (ECM). The final mature SPARC protein has 286 amino acids
      with three distinct domains, including an NH2-terminal acidic domain (NT),
      follistatin-like domain (FS) and C terminus domain (EC). The present study
      identified SPARC genes from 14 vertebrate genomes and revealed that SPARC existed
      in all types of vertebrates, including fish, amphibians, birds and mammals. In
      total, 21 single nucleotide polymorphisms (SNPs) causing missense mutations were
      identified, which may affect the formation of the truncated form of the SPARC
      protein. The human SPARC gene was found to be expressed in numerous tissues or
      organs, including in the bone marrow, whole blood, lymph node, thymus, brain,
      cerebellum, retina, heart, smooth muscle, skeletal muscle, spinal cord,
      intestine, colon, adipocyte, kidney, liver, pancreas, thyroid, salivary gland,
      skin, ovary, uterus, placenta, cervix and prostate. When searched in the
      PrognoScan database, the human SPARC gene was also found to be expressed in
      bladder, blood, breast, glioma, esophagus, colorectal, head and neck, ovarian,
      lung and skin cancer tissues. It was revealed that the association between the
      expression of SPARC and prognosis varied in different types of cancer, and even
      in the same cancer from different databases. It implied that the function of
      SPARC in these tumors may be multidimensional, functioning not just as a tumor
      suppressor or oncogene.

PMID- 24938429
TI  - Photoinduced water splitting with oxotitanium tetraphenylporphyrin.
AB  - Photocatalytic splitting of water was investigated in a heterogeneous system
      consisting of micro-crystallites of oxotitanium tetraphenylporphyrin deposited on
      fused silica plates, immersed in water and excited within the visible range of
      their absorption spectra. The water photolysis was evidenced by the spectroscopic
      detection of hydroxyl radicals generated in the reaction. The experimental
      results confirm the mechanism of water splitting and generation of OH radicals
      proposed theoretically by Sobolewski and Domcke [Phys. Chem. Chem. Phys., 2012,
      14, 12807] for the oxotitaniumporphyrin-water complex. It is shown that
      photocatalytic water splitting occurs in pure water, and neither pH-bias nor
      external voltage is required to promote the reaction. 

PMID- 24938428
TI  - Analysis of interactions between SNARE proteins using imaging ellipsometer
      coupled with microfluidic array.
AB  - The soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)
      proteins are small and abundant membrane-bound proteins, whose specific
      interactions mediate membrane fusion during cell fusion or cellular trafficking.
      In this study, we report the use of a label-free method, called imaging
      ellipsometer to analyze the interactions among three SNAREs, namely Sec22p, Ykt6p
      and Sso2p. The SNAREs were immobilized on the silicon wafer and then analyzed in
      a pairwise mode with microfluidic array, leading us to discover the interactions
      between Ykt6p and Sso2p, Sec22p and Sso2p. Moreover, by using the real-time
      function of the imaging ellipsometer, we were able to obtain their association
      constants (K(A)) of about 10(4) M(-1). We argue that the use of imaging
      ellipsometer coupled with microfluidic device will deepen our understanding of
      the molecular mechanisms underlying membrane fusion process.

PMID- 24938430
TI  - Author's response re: letter to the editor re: Martinez-Garcia R, Ubeda-Sansano
      MI, Diez-Domingo J, Perez-Hoyos S, Gil-Salom M. It is time to abandon "expected
      bladder capacity." Systematic review and new models for children's normal maximum
      voided volumes. Neurourol Urodyn 2013;33:1099.

PMID- 24938431
TI  - Setting standards for severity of common symptoms in oncology using the PROMIS
      item banks and expert judgment.
AB  - BACKGROUND: Although the use of patient-reported outcome measures (PROs) has
      increased markedly, clinical interpretation of scores remains lacking. We
      developed a method to identify clinical severity thresholds for pain, fatigue,
      depression, and anxiety in people with cancer. METHODS: Using available Patient
      Reported Outcomes Measurement Information System (PROMIS) item bank response data
      collected on 840 cancer patients, symptom vignettes across a range of symptom
      severity were developed and placed on index cards. Cards represented symptom
      severity at five-point intervals differences on the T score metric [mean = 50;
      standard deviation (SD) = 10]. Symptom vignettes for each symptom were anchored
      on these standardized scores at 0.5 SD increments across the full range of
      severity. Clinical experts, blind to the PROMIS score associated with each
      vignette, rank-ordered the vignettes by severity, then arrived at consensus
      regarding which two vignettes were at the upper and lower boundaries of normal
      and mildly symptomatic for each symptom. The procedure was repeated to identify
      cut scores separating mildly from moderately symptomatic, and moderately from
      severely symptomatic scores. Clinician severity rankings were then compared to
      the T scores upon which the vignettes were based. RESULTS: For each of the
      targeted PROs, the severity rankings reached by clinician consensus perfectly
      matched the numerical rankings of their associated T scores. Across all symptoms,
      the thresholds (cut scores) identified to differentiate normal from mildly
      symptomatic were near a T score of 50. Cut scores differentiating mildly from
      moderately symptomatic were at or near 60, and those separating moderately from
      severely symptomatic were at or near 70. CONCLUSIONS: The study results provide
      empirically generated PROMIS T score thresholds that differentiate levels of
      symptom severity for pain interference, fatigue, anxiety, and depression. The
      convergence of clinical judgment with self-reported patient severity scores
      supports the validity of this methodology to derive clinically relevant symptom
      severity levels for PROMIS symptom measures in other settings.

PMID- 24938432
TI  - Copper-catalyzed one-pot trifluoromethylation/aryl migration/carbonyl formation
      with homopropargylic alcohols.
AB  - A novel copper-catalyzed one-pot functionalization of homopropargylic alcohols
      that involves trifluoromethylation, aryl migration, and formation of a carbonyl
      moiety has been developed. This reaction constitutes the first direct conversion
      of homopropargylic alcohols into CF3-containing 3-butenal or 3-buten-1-one
      derivatives in a regioselective manner. Mechanistic studies indicate that the 1,4
      aryl migration proceeds through a radical pathway.

PMID- 24938433
TI  - Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.
AB  - PURPOSE: This study was designed to investigate the role of PDGF-DD secreted by
      gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer
      progression. METHODS: Gastric cancer cells were indirectly co-cultured with GC
      MSCs in a transwell system. The growth and migration of gastric cancer cells were
      evaluated by cell colony formation assay and transwell migration assay,
      respectively. The production of PDGF-DD in GC-MSCs was determined by using
      Luminex and ELISA. Neutralization of PDGFR-beta by su16f and siRNA interference
      of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC
      MSCs in gastric cancer progression. RESULTS: GC-MSC conditioned medium promoted
      gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture
      with GC-MSCs increased the phosphorylation of PDGFR-beta in SGC-7901 cells.
      Neutralization of PDGFR-beta by su16f blocked the promoting role of GC-MSC
      conditioned medium in gastric cancer cell proliferation and migration.
      Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on
      gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on
      gastric cancer cells in vitro and in vivo. CONCLUSIONS: PDGF-DD secreted by GC
      MSCs is capable of promoting gastric cancer cell progression in vitro and in
      vivo. Targeting the PDGF-DD/PDGFR-beta interaction between MSCs and gastric
      cancer cells may represent a novel strategy for gastric cancer therapy.

PMID- 24938434
TI  - Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in
      high-risk prostate cancer.
AB  - PURPOSE: To explore differential methylation of HAAO, HOXD3, LGALS3, PITX2,
      RASSF1 and TDRD1 as a molecular tool to predict biochemical recurrence (BCR) in
      patients with high-risk prostate cancer (PCa). METHODS: A multiplexed nested
      methylation-specific PCR was applied to quantify promoter methylation of the
      selected markers in five cell lines, 42 benign prostatic hyperplasia (BPH) and 71
      high-risk PCa tumor samples. Uni- and multivariate Cox regression models were
      used to assess the importance of the methylation level in predicting BCR.
      RESULTS: A PCa-specific methylation marker HAAO in combination with HOXD3 and a
      hypomethylation marker TDRD1 distinguished PCa samples (>90 % of tumor cells
      each) from BPH with a sensitivity of 0.99 and a specificity of 0.95. High
      methylation of PITX2, HOXD3 and RASSF1, as well as low methylation of TDRD1,
      appeared to be significantly associated with a higher risk for BCR (HR 3.96,
      3.44, 2.80 and 2.85, correspondingly) after correcting for established risk
      factors. When DNA methylation was treated as a continuous variable, a two-gene
      model PITX2 * 0.020677 + HOXD3 * 0.0043132 proved to be the best predictor of BCR
      (HR 4.85) compared with the individual markers. This finding was confirmed in an
      independent set of 52 high-risk PCa tumor samples (HR 11.89). CONCLUSIONS:
      Differential promoter methylation of HOXD3, PITX2, RASSF1 and TDRD1 emerges as an
      independent predictor of BCR in high-risk PCa patients. A two-gene continuous DNA
      methylation model "PITX2 * 0.020677 + HOXD3 * 0.0043132" is a better predictor of
      BCR compared with individual markers.

PMID- 24938435
TI  - Complement components, proteolysis-related, and cell communication-related
      proteins detected in urine proteomics are associated with IgA nephropathy.
AB  - INTRODUCTION: IgA nephropathy (IgAN) is the most common primary
      glomerulonephritis. The first symptoms of IgAN are erytrocyturia or hematuria,
      proteinuria, and decline in renal function, or any combination of the above. One
      of the promising diagnostic methods is urine proteomics. OBJECTIVES: We studied
      urine proteomics in patients with IgAN and age- and sex-matched healthy controls.
      To minimize the risk of protein degradation, we proposed a new protocol for urine
      collection and preparation. PATIENTS AND METHODS: A total of 30 patients with
      IgAN and 30 controls were enrolled into the study. Thirty urine samples of the
      IgAN group were divided into 3 disease pooled samples (DPS I, II, and III) and 30
      urine samples of the control group were divided into 3 control pooled samples
      (CPS I, II, and III). We used isoelectric focusing/liquid chromatography-mass
      spectrometry/mass spectrometry (IEF/LC-MS/MS) to detect all proteins larger than
      10 kDa. RESULTS: Using qualitative analysis, we identified 761, 951, and 956
      proteins in each of the 3 IEF/LC-MS/MS experiments. The results were combined,
      yielding a dataset with 1238 proteins identified by at least 2 peptides. The
      statistical analysis of the quantitative results revealed 18 proteins that were
      differently populated in the urine of IgAN patients compared with healthy
      controls. We found increased urinary concentrations of complement components,
      coagulation factors, extracellular matrix, intracellular, transmembrane, and
      other proteins in patients with IgAN. Some of them have never been linked to IgAN
      before. CONCLUSIONS: We demonstrated that urine proteomics is a promising tool
      for diagnosing and monitoring patients with IgAN.

PMID- 24938436
TI  - Transposable elements: ERE and there for pluripotency.

PMID- 24938439
TI  - Synergistic role of self-emulsifying lipids and nanostructured porous silica
      particles in optimizing the oral delivery of lovastatin.
AB  - AIM: To investigate the role of self-emulsifying lipids and porous silica
      particles in enhancing supersaturated drug loading and biopharmaceutical
      performance of nanostructured silica-lipid hybrid (SLH) systems. MATERIALS &
      METHODS: Two lovastatin (LOV)-SLHs were engineered from self-emulsifying lipid
      (Gelucire((r)) 44/14; Gattefosse, Lyon, France) and Aerosil((r)) 380 (SLH-A;
      Evonik Industries, Essen, Germany) or Syloid((r)) 244FP silica (SLH-S; Grace
      Davison Discovery Sciences, Rowville, Australia). RESULTS & DISCUSSION: The LOV
      SLHs encapsulated LOV at 10% w/w, which is >=3-fold higher than typical lipid
      formulations in the absence of porous silica. The LOV-SLHs retained self
      emulsifying lipid-associated solubilization benefits and improved drug
      solubilization by twofold in simulated intestinal condition. SLH-S, with larger
      surface area (299 m(2)/g), was superior to SLH-A (184 m(2)/g) in optimizing oral
      bioavailability, suggesting a critical role of the silica geometry.
      Bioavailability of SLH-S was 2.8- and 1.3-fold higher than pure drug and drug
      suspension in Gelucire 44/14, respectively. CONCLUSION: In conclusion, SLHs
      profit from advantages associated with both self-emulsifying lipids and porous
      silica, and provide potentially improved therapy against coronary artery disease.

PMID- 24938440
TI  - Ayurvedic medicine for rheumatoid arthritis.
AB  - Ayurvedic medicine is the traditional medicine of India, which originated over
      5,000 years ago. Parts of this alternative medical system have become
      increasingly popular worldwide as patients seek approaches to medical care that
      they perceive as more holistic and less toxic than those offered by conventional
      Western medicine. Despite the advent of highly effective pharmacologic therapy,
      most individuals with rheumatoid arthritis (RA) continue to use alternative
      therapy at some point in the treatment of their disease. This report discusses
      some of the in-vitro data that suggest potential mechanisms through which
      Ayurvedic herbal medicines might have beneficial actions in rheumatoid arthritis,
      and the available clinical data evaluating the use of Ayurvedic medicine for RA. 

PMID- 24938441
TI  - Use of DXA-based technology for detection and assessment of risk of vertebral
      fracture in rheumatology practice.
AB  - Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry
      (DXA) is the recommended method for diagnosis of osteoporosis and assessment of
      future fracture risk. However, most patients who will suffer fractures do not
      have osteoporosis by DXA (T-score of -2.5 or less). Bone strength, which is most
      closely associated with resistance to fracture, is a composite of both bone
      density and bone quality, and the latter is not measured by DXA. Thus, other
      technology is needed for non-invasive and inexpensive assessment of bone strength
      and fracture risk. Vertebral fractures, the most common clinical fracture in the
      general population, are of even greater importance in rheumatoid arthritis and
      other rheumatic disorders. Vertebral fracture assessment (VFA) and trabecular
      bone scores (TBS), two techniques which can aid prediction of future fracture
      risk, can be used with currently available DXA machines. Description of these
      techniques and their potential application to clinical rheumatology practice will
      be the focus of this paper. 

PMID- 24938442
TI  - Treatment of uveitis associated with juvenile idiopathic arthritis.
AB  - Chronic anterior uveitis affects 10-30 % of patients with juvenile idiopathic
      arthritis (JIA) and is still a cause of blindness in childhood. In most patients
      it is asymptomatic, bilateral, and recurrent, so careful screening and early
      diagnosis are important to obtain the best long-term prognosis. The treatment of
      chronic uveitis associated with JIA is challenging. Initial treatment is based on
      topical steroids and mydriatic drops. Methotrexate is the most common first-line
      immunomodulatory drug used. For refractory patients, biologicals, mainly the anti
      tumor-necrosis-factor (TNF) drugs adalimumab and infliximab, have been revealed
      to be effective and have changed the outcome for these patients. Collaboration
      between pediatric rheumatologists and ophthalmologists is important for the
      successful diagnosis and treatment of patients with uveitis associated with JIA. 

PMID- 24938444
TI  - Xiaoji Decoction inhibited cell proliferation and induced apoptosis through Akt
      signaling pathway in human lung cancer A549 cells.
AB  - OBJECTIVE: To investigate the inhibitive effect and the underlying mechanism of
      Xiaoji Decoction (, XJD) in human lung cancer A549 cells. METHODS: A549 cells in
      logarithmic proliferation were cultivated in RPMI-1640 containing 10% low, medium
      or high dosages of XJD serum. The inhibitive effect of XJD in A549 cell
      proliferation was assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT)
      assay. The pro-apoptotic effect of XJD in A549 cells was observed by fluorescence
      microscope via Hoechst 33258 staining. The role of the Akt signaling pathway was
      observed by examining the presence of p-Akt protein by Western blot and the mRNA
      expression of downstream proteins such as Bcl-2/Bcl-XL-associated death promoter
      (BAD) and caspase-9 by real time polymerase chain reaction. RESULTS: MTT assay
      revealed that XJD could inhibit A549 proliferation in a dose- and time-dependent
      manner. Hoechst 33258 staining showed that XJD induced the typical nuclear
      apoptotic morphology after XJD treatment. Moreover, XJD could reduce the
      phosphorylation of Akt and increase the mRNA expression of BAD and caspase-9.
      CONCLUSIONS: XJD can inhibit the proliferation of A549 cells in a dose- and time
      dependent manner through signaling Akt pathway via up-regulating the expression
      of BAD and caspase-9. XJD may provide a novel therapeutic model for lung cancer
      and deserve further study.

PMID- 24938443
TI  - Conditions for production of interdisciplinary teamwork outcomes in oncology
      teams: protocol for a realist evaluation.
AB  - BACKGROUND: Interdisciplinary teamwork (ITW) is designed to promote the active
      participation of several disciplines in delivering comprehensive cancer care to
      patients. ITW provides mechanisms to support continuous communication among care
      providers, optimize professionals' participation in clinical decision-making
      within and across disciplines, and foster care coordination along the cancer
      trajectory. However, ITW mechanisms are not activated optimally by all teams,
      resulting in a gap between desired outcomes of ITW and actual outcomes observed.
      The aim of the present study is to identify the conditions underlying outcome
      production by ITW in local oncology teams. METHODS: This retrospective multiple
      case study will draw upon realist evaluation principles to explore associations
      among context, mechanisms and outcomes (CMO). The cases are nine
      interdisciplinary cancer teams that participated in a previous study evaluating
      ITW outcomes. Qualitative data sources will be used to construct a picture of CMO
      associations in each case. For data collection, reflexive focus groups will be
      held to capture patients' and professionals' perspectives on ITW, using the
      guiding question, 'What works, for whom, and under what circumstances?' Intra
      case analysis will be used to trace associations between context, ITW mechanisms,
      and patient outcomes. Inter-case analysis will be used to compare the different
      cases' CMO associations for a better understanding of the phenomenon under study.
      DISCUSSION: This multiple case study will use realist evaluation principles to
      draw lessons about how certain contexts are more or less likely to produce
      particular outcomes. The results will make it possible to target more
      specifically the actions required to optimize structures and to activate the best
      mechanisms to meet the needs of cancer patients. This project could also
      contribute significantly to the development of improved research methods for
      conducting realist evaluations of complex healthcare interventions. To our
      knowledge, this study is the first to use CMO associations to improved empirical
      and theoretical understanding of interdisciplinary teamwork in oncology, and its
      results could foster more effective implementation in clinical practice.

PMID- 24938447
TI  - Protective effect of Tianqi Hangli Recipe () extract on high sustained positive
      acceleration stress-induced myocardial mitochondrial injury in rats.
AB  - OBJECTIVE: To explore the protective effect of Tianqi Hangli Recipe () extract
      (THRE) on high sustained positive acceleration (+Gz) stress-induced myocardial
      mitochondrial injury in rats. METHODS: Seventy-two male SD rats were randomly
      assigned to various groups with 12 rats per group: blank control group, stress
      control group, high +Gz stress group, low-dose THRE group (0.75 g/kg), medium
      dose THRE group (1.5 g/kg) and high dose THRE group (3.0 g/kg). Each rat was fifi
      rstly fed with 20 mL/kg menstruum once a day for 14 days. The rats were then
      exposed to high +Gz at the 15th day. Myocardial mitochondrial structure,
      respiratory function, antioxidant capacity and ATPases activities were examined
      for the comparison after the high +Gz exposure. RESULTS: The rats treated with
      high +Gz stress showed signififi cant pathological changes: the myocardial
      mitochondria were swelled, degenerated and decreased, and mitochondrial cristae
      were broken or disappeared. State 3 respiration and the respiratory control ratio
      (RCR) were both significantly lower, and state 4 respiration was higher as
      compared with the blank control group and stress control groups (P <0.01, P
      <0.05). In addition, the activities of its antioxidant enzymes [superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px)] and Na+-K+-ATPase were also
      decreased (P <0.01 or P <0.05), but the formation of malondialdehyde (MDA) was
      increased (P <0.01). However, THRE preconditioning could attenuate mitochondrial
      structural damages and reverse the high +Gz stress-caused changes of parameters
      about respiration, antioxidant enzymes and ATPases, most of which had no
      significant difference between the high-dose THRE group and the stress control
      group. CONCLUSION: THRE can protect high sustained +Gz stress-induced myocardial
      mitochondrial injury in rats as was shown to ameliorate respiratory function and
      increase activities of antioxidant enzymes and ATPases.

PMID- 24938445
TI  - Current research and future directions in pattern identification: Results of an
      international symposium.
AB  - A symposium on pattern identification (PI) was held at the Korea Institute of
      Oriental Medicine (KIOM) on October 2, 2013, in Daejeon, South Korea. This
      symposium was convened to provide information on the current research in PI as
      well as suggest future research directions. The participants discussed the nature
      of PI, possible research questions, strategies and future international
      collaborations in pattern research. With eight presentations and an extensive
      panel discussion, the symposium allowed participants to discuss research methods
      in traditional medicine for PI. One speaker presented the topic, 'Clinical
      pattern differentiation and contemporary research in PI.' Two speakers presented
      current trends in research on blood stasis while the remaining five other
      delegates discussed the research methods and future directions of PI research.
      The participants engaged in in-depth discussions regarding the nature of PI,
      potential research questions, strategies and future international collaborations
      in pattern research.

PMID- 24938446
TI  - Appraisal of clinical practice guidelines for ischemic stroke management in
      Chinese medicine with appraisal of guidelines for research and evaluation
      instrument: A systematic review.
AB  - OBJECTIVE: To systematically review the clinical practice guidelines (CPGs) for
      ischemic stroke in Chinese medicine (CM) with the Appraisal of Guidelines for
      Research and Evaluation (AGREE II) instrument. METHODS: CM CPGs for ischemic
      stroke were searched in 5 online databases and hand-searches in CPGrelated
      handbooks published from January 1990 to December 2012. The CPGs were categorized
      into evidence based (EB) guideline, consensus based with no explicit
      consideration of evidence based (CB-EB) guideline and consensus based (CB)
      guideline according to the development method. Three reviewers independently
      appraised the CPGs based on AGREE II instrument, and compared the CPGs'
      recommendations on CM pattern classification and treatment. RESULTS: Five CM CPGs
      for ischemic stroke were identified and included. Among them, one CPG was EB
      guideline, two were CB guidelines and two were CB-EB guidelines. The quality
      score of the EB guideline was higher than those of the CB-EB and CB guidelines.
      Five CM patterns in the CPGs were recommended in the EB CPG. The comprehensive
      protocol of integrative Chinese and Western medicine recommended in the EB CPG
      was mostly recommended for ischemic stroke in the CPGs. The recommendations
      varied based on the CM patterns. CONCLUSION: The quality of EB CPG was higher
      than those of CB and CB-EB CPGs in CM for ischemic stroke and integrative
      approaches were included in CPGs as major interventions.

PMID- 24938448
TI  - The association between pulmonary function impairment and colon inflammation in
      ulcerative colitis patients: A scientific basis for exterior-interior correlation
      between lung and large intestine.
AB  - OBJECTIVE: To investigated the involvement of pulmonary function impairment in
      ulcerative colitis (UC), to explore a scientific basis for the Chinese medicine
      (CM) theory of exterior-interior correlation between Lung (Fei) and Large
      intestine (Dachang). METHODS: Totally 120 patients with a diagnosis of UC were
      recruited and the demographics, clinical data, and blood samples were collected.
      C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) concentrations
      were measured. Every patient accepted pulmonary function test and took chest
      radiograph (CXR).> RESULTS: Pulmonary function abnormalities were present in 72
      of 120 patients. The median (interquartile range) vital capacity (VC), forced
      vital capacity (FVC), forced expiratory volume in 1 s (FEV1), carbon monoxide
      diffusion capacity (DLCO) of lung, total lung capacity (TLC) and functional
      residual volume (FRV) were decreased in distal UC and pancolitis compared with
      ulcerative prochitis (P <0.0005). Male patients had increased VC, FEV1/FVC, and
      residual volume (RV)/TLC compared with female (P <0.0005), but decreased DLCO and
      carbon monoxide iffusion capacity (KCO) of lung/alveolar ventilation (P <0.0005).
      Age was strongly correlated with RV (Spearman rank correlation coefficient (rs)=
      0.57,P <0.0001), and RV/TLC (rs=0.48,P<0.0001). Age was also correlated with
      FEV1/FVC (rs=-0.29, P=0.001), forced expiratory flow in 75% vital capacity
      (FEF75%, rs=-0.20, P=0.03), DLCO (rs=-0.21, P=0.02), TLC (rs=-0.25, P=0.006), and
      FRV (rs=-0.28, P=0.002). The course of disease was correlated with FEF75% (rs=
      0.18, P=0.049) and KCO (rs=-0.19, P=0.036). Chest radiograph abnormalities were
      presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other
      extraintestinal complications were presented in 21 of 120. CONCLUSIONS: Pulmonary
      function impairment was more frequently than other extraintestinal complications
      in UC patients, which may be affected by sex, age, extent and course of disease.
      These results may be a scientific basis for the theory of exterior-interior
      correlation between Lung and Large intestine.

PMID- 24938449
TI  - Effect of Longbishu capsule () plus doxazosin on benign prostatic hyperplasia: a
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of Longbishu Capsule (, LBS), doxazosin, and
      combination therapy on benign prostatic hyperplasia (BPH). METHODS: A randomized,
      double-blind, multi-center parallel trial was conducted involving 360 patients in
      hospitals in Beijing (108 cases), Heilongjiang (90 cases), Sichuan (90 cases),
      Shanghai (72 cases), China. They were randomly assigned with central
      randomization method to group A (LBS placebo plus doxazosin), group B (LBS plus
      doxazosin) or group C (LBS plus doxazosin placebo), 120 cases for each group. The
      international prostate symptom score, maximum urinary flow rate, postvoid
      residual urine volume and prostate volume were measured for evaluating the
      efficacy of the three treatments. RESULTS: At baseline, there was no significant
      difference in the measured variables among the three groups. After 12-month
      treatment, the three groups showed significant improvements in IPSS and maximum
      urinary flow rate from baseline (P<0.01). Although postvoid residual urine volume
      was not significantly different from the baseline in group A (P>0.05), it
      significantly decreased in group B and C (P<0.05). The incidence of adverse
      events were similar among the three groups. CONCLUSIONS: The treatment of LBS
      alone or LBS plus doxazosin was able to significantly improve IPSS in patients
      with BPH. The treatments may reduce the increase in prostate volume and postvoid
      residual urine volume as well.

PMID- 24938451
TI  - Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced
      by oral metronidazole.
AB  - Baboon syndrome is a special form of systemic contact dermatitis to systemic or
      local administration of contact allergens. Baboon syndrome without known previous
      cutaneous sensitisation was also described as drug-related baboon syndrome or
      symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The
      major drugs causing SDRIFE was beta-lactam antibiotic such as amoxicillin and
      ampicillin. We report a case of 16-year-old woman who developed pruritic
      eruptions after oral metronidazole treatment for diarrhea. She was diagnosed
      SDRIFE according to her clinical and histopathological findings. To our
      knowledge, our patient is the first case who developed SDRIFE due to
      metronidazole in the literature.

PMID- 24938450
TI  - Anticancer effect of total annonaceous acetogenins on hepatocarcinoma.
AB  - OBJECTIVE: To confirm the anticancer effect of total annonaceous acetogenins
      (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma. METHODS:
      The inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency
      of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell
      under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as
      cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and
      recipient apoptotic pathways were differentiated as mitochondrial membrane
      potential under flow cytometry and caspases activities under fluorescence
      analysis. RESULTS: The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg
      dose. The IC50 of TAAs on Bel-7402 was 20.06 ug/mL (15.13-26.61ug/mL). Effective
      mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and
      inducing apoptosis dose- and time-dependently. Mitochondrial and recipient
      pathways involved in apoptotic actions of TAAs. CONCLUSION: TAAs is effective for
      hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.

PMID- 24938452
TI  - The effect of antihypertensive therapy on dry eye disease.
AB  - CONTEXT: There is a generalization that "antihypertensive (antiHT) therapy causes
      Dry Eye Syndrome", which has been claimed for years however most of the
      publications are epidemiological studies. We performed a clinical study to
      investigate the effects of antiHT agents on tear function. OBJECTIVE: The aim of
      this article is to evaluate the effects of different classes of antiHT
      medications on tear osmolarity, ocular surface problems and dry eye symptoms.
      MATERIALS AND METHODS: Prospective, non-randomized a clinical study. A total of
      71 patients who would be initiated antiHT medication due to elevated systemic
      blood pressure were included in the study. Thirty of these patients were given
      antiHT drugs containing diuretic (diuretic +), and 41 of them were given diuretic
      free drugs (diuretic -). While the number of the patients medicated in the group
      that received Angiotensin Converting Enzyme inhibitors (ACE inh)/Angiotensin
      receptor blockers (ARB) (ACE/ARB +) was 29, the number of those medicated in the
      ACE/ARB-free group (ACE/ARB -) was 42. Ocular surface disease index scores, tear
      osmolarity, Schirmer I test, tear film break-up time (TBUT), fluorescein (FL) and
      rose bengal corneal staining patterns of the patients were analyzed. The patients
      were examined through the repetition of all the tests in the 1st and the 3rd
      month. RESULTS: The participants (n = 71) comprised 38 males and 33 females with
      a mean age of 51.8 +/- 10.4. When the first (0-1st month) and the third month (0
      3rd months) control measurements between diuretics (+) and diuretics (-) groups
      before and after antiHT therapies were compared, a statistically significant
      difference was not found in any of the tests applied. When the 0-1st month
      measurements of ACE/ARB (+) and ACE/ARB (-) groups were compared, it was observed
      that staining with FL in ACE/ARB (+) group decreased in a statistically
      significant manner (p = 0.035) and there was a significant increase in TBUT
      values (p = 0.022). DISCUSSION AND CONCLUSION: The use of antiHT drugs containing
      diuretic had no adverse effect on the tear function tests, but using drugs that
      contain ACE/ARB could have a positive impact.

PMID- 24938453
TI  - An open, comparative clinical study on the efficacy and safety of 10%
      trichloroacetic acid, 25% trichloroacetic acid and cryotherapy for verruca plana.
AB  - OBJECTIVE: Although there are several methods to treat Verruca plana, warts do
      not respond well to the common therapeutic options. In this study, we compared
      the safety and efficacy of 10% trichloroacetic acid, 25% trichloroacetic acid,
      and cryotherapy for the treatment of warts caused by Verruca plana. METHODS: Ten
      percent and 25% trichloroacetic acid were applied to warts weekly until all
      lesions cleared. Cryotherapy was performed by liquid nitrogen spray for 5-10
      seconds for each lesion per week until the lesions cleared. The number of Verruca
      plana lesions and adverse effects were evaluated five times during the treatment
      (the initial visit, week 2, week 4, week 6, and week 8). RESULTS: The number of
      lesions decreased through week 8 for all three treatments, and the reductions in
      the mean numbers of lesions were statistically similar (p > 0.05). Those in the
      cryotherapy group exhibited more erythema, pain, erosions, bullae, and
      hyperpigmentation (p < 0.001, p < 0.001, p < 0.001, p < 0.05, and p = 0.001,
      respectively) than those in either TCA group. Itching was more common among those
      in the trichloroacetic acid groups than in the cryotherapy group (p < 0.05).
      Additionally, hyperpigmentation, erythema, pain, and itching were more frequent
      in the 25% trichloroacetic acid group than in the 10% trichloroacetic acid group
      (p < 0.001), (p < 0.05), (p < 0.05), (p < 0.05). CONCLUSION: Ten percent
      trichloroacetic acid, 25% trichloroacetic acid, and cryotherapy are effective
      methods to treat Verruca plana. 10% trichloroacetic acid offers a safer and
      easier treatment than either 25% trichloroacetic acid or cryotherapy.

PMID- 24938454
TI  - Lichen striatus: after a bite by bumblebee.
AB  - Lichen striatus (LS) is an uncommon dermatosis characterised by a linear
      inflammatory papular eruption. It is frequently seen in children and rarely in
      adults. We present in this study a 49-year-old female patient who was diagnosed
      as LS, which occurs after a bite by bumblebee. As we know, it is the first case
      of LS reported after a bite by bumblebee. 

PMID- 24938455
TI  - Gentamicin affects melanogenesis in normal human melanocytes.
AB  - BACKGROUND: Aminoglycoside antibiotics, including gentamicin, despite their
      ability to induce adverse effects on pigmented tissues, remain valuable and
      sometimes indispensable for the treatment of various infections. It is known that
      gentamicin binds to melanin biopolymers, but the relation between this drug
      affinity to melanin and its toxicity is not well documented. The aim of this work
      was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP
      (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes.
      METHODOLOGY/PRINCIPAL FINDINGS: The effect of gentamicin on cell viability was
      determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene
      disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured
      spectrophotometrically. It has been demonstrated that gentamicin induces
      concentration-dependent loss in melanocytes viability. The application of
      antibiotic in concentration of 10 mM causes higher reduction in viability of the
      light pigmented melanocytes (by about 74%) when compared with the dark pigmented
      ones (by about 62%). The value of the concentration of a drug that produces loss
      in cell viability by 50% (EC50) for both cell lines was found to be ~7.5 mM. It
      has been shown that gentamicin causes inhibition of tyrosinase activity and
      reduces melanin content in light pigmented melanocytes significantly more than in
      the dark pigmented cells. CONCLUSION/SIGNIFICANCE: We have found that gentamicin
      modulates melanization process in melanocytes in vitro, what may explain the
      potential role of melanin biopolymer in the mechanisms of undesirable toxic
      effects of this drug in vivo, as a result of its accumulation in pigmented
      tissues. We have also stated that the melanogenesis process in light pigmented
      melanocytes is more sensitive to the inhibitory effect of gentamicin than in the
      dark pigmented cells.

PMID- 24938456
TI  - Targeting macrophage subsets for infarct repair.
AB  - Macrophages are involved in every cardiovascular disease and are an attractive
      therapeutic target. Macrophage activation is complex and can be either beneficial
      or deleterious, depending upon its mode of action, its timing, and its duration.
      An important macrophage characteristic is its plasticity, which enables it to
      switch from one subset to another. Macrophages, which regulate healing and repair
      after myocardial infarction, have become a major target for both treatment and
      diagnosis (theranostic). The aim of the present review is to describe the recent
      discoveries related to targeting and modulating of macrophage function to improve
      infarct repair. We will briefly review macrophage polarization, plasticity,
      heterogeneity, their role in infarct repair, regeneration, and cross talk with
      mesenchymal cells. Particularly, we will focus on the potential of macrophage
      targeting in situ by liposomes. The ability to modulate macrophage function could
      delineate pathways to reactivate the endogenous programs of myocardial
      regeneration. This will eventually lead to development of small molecules or
      biologics to enhance the endogenous programs of regeneration and repair. 

PMID- 24938457
TI  - Proprotein convertase subtilisin/kexin 9 inhibitors: an emerging lipid-lowering
      therapy?
AB  - Proprotein convertase subtilisin/kexin 9 (PCSK9) is part of the proteinase K
      subfamily of subtilases and plays a key role in lipid metabolism. It increases
      degradation of the low-density lipoprotein receptor (LDL-R), modulates
      cholesterol metabolism and transport, and contributes to the production of
      apolipoprotein B (apoB) in intestinal cells. Exogenous PCSK9 modifies the
      activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acyl coenzyme
      A:cholesterol acyltransferase and enhances secretion of chylomicrons by
      modulating production of lipids and apoB-48. Statins increase PCSK9 messenger RNA
      expression and attenuate the capacity to increase LDL-R levels. Therefore, the
      inhibition of PCSK9 in combination with statins provides a promising approach for
      lowering low-density lipoprotein cholesterol (LDL-C) concentrations. This review
      will address new therapeutic strategies targeting PCSK9, including monoclonal
      antibodies, antisense oligonucleotides, small interfering RNAs, and other small
      molecule inhibitors. Further studies are still needed to determine the efficacy
      and safety of the PCSK9 inhibitors not only to decrease LDL-C but also to
      investigate the potential underlying mechanisms involved and to test whether
      these compounds actually reduce cardiovascular end points and mortality. 

PMID- 24938458
TI  - Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through
      downregulation of VE-cadherin/EphA2/MMP9/MMP2 expression.
AB  - Ginsenoside Rg3 (Rg3), a trace tetracyclic triterpenoid saponin, is extracted
      from ginseng and shown to have anticancer activity against several types of
      cancers. This study explored the effect of Rg3 on pancreatic cancer vasculogenic
      mimicry. Altered vasculogenic mimicry formation was assessed using
      immunohistochemistry and PAS staining and associated with the expression of
      vascular endothelial-cadherin (VE-cadherin), epithelial cell kinase (EphA2),
      matrix metalloproteinase (MMP)-2 and MMP-9. The effect of Rg3 on the regulation
      of pancreatic cancer vasculogenic mimicry was evaluated in vitro and in vivo. The
      data showed vasculogenic mimicry in pancreatic cancer tissues. In addition, the
      expression of VE-cadherin, EphA2, MMP-2 and MMP-9 proteins associated with
      formation of pancreatic cancer vasculogenic mimicry. Rg3 treatment reduced the
      levels of vasculogenic mimicry in nude mouse xenografts in vitro and in vivo,
      while the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 mRNA and proteins was
      downregulated by Rg3 treatment in vitro and in tumor xenografts. In conclusion,
      ginsenoside Rg3 effectively inhibited the formation of pancreatic cancer
      vasculogenic mimicry by downregulating the expression of VE-cadherin, EphA2, MMP9
      and MMP2. Further studies are required to evaluate ginsenoside Rg3 as an agent to
      control pancreatic cancer.

PMID- 24938459
TI  - Prevalence and incidence of hand eczema in adolescence: report from BAMSE--a
      population-based birth cohort.
AB  - BACKGROUND: BAMSE is a Swedish population-based birth cohort. OBJECTIVES: To
      estimate prevalence proportions and the incidence rate of hand eczema in Swedish
      adolescents, and to compare information given by adolescents and parents. Further
      aims were to study sex distribution, age at onset and extension of hand eczema.
      METHODS: At 16 years of age, 2927 adolescents were included in this study; both
      adolescent and parental questionnaires were used, as well as clinical
      examination. RESULTS: The 1-year prevalence of hand eczema was 5.2% (n = 152) and
      4.0% (n = 116) (P < 0.03), and lifetime prevalence was 9.7% (n = 284) and 7.0% (n
      = 206) (P < 0.01), respectively, when adolescents and parents reported. The
      incidence rate was 573/100 000 person-years according to the adolescent report.
      The level of agreement between adolescents and parents was fair for 1-year and
      lifetime prevalence (kappa = 0.56 and kappa = 0.49, respectively). According to
      the Hand Eczema Extent Score, 27.0% (n = 36) had moderate-to-severe hand eczema.
      CONCLUSIONS: At the age of 16 years, the 1-year prevalence of hand eczema was
      substantial, with an incidence rate of the same magnitude as in adults. Female
      predominance was seen in adolescence. It is preferable that the occurrence of
      hand eczema is reported by adolescents themselves, as they are the ones most
      aware of their symptoms.

PMID- 24938460
TI  - HRM and its effect on employee, organizational and financial outcomes in health
      care organizations.
AB  - BACKGROUND: One of the main goals of Human Resource Management (HRM) is to
      increase the performance of organizations. However, few studies have explicitly
      addressed the multidimensional character of performance and linked HR practices
      to various outcome dimensions. This study therefore adds to the literature by
      relating HR practices to three outcome dimensions: financial, organizational and
      employee (HR) outcomes. Furthermore, we will analyze how HR practices influence
      these outcome dimensions, focusing on the mediating role of job satisfaction.
      METHODS: This study uses a unique dataset, based on the 'ActiZ Benchmark in
      Healthcare', a benchmark study conducted in Dutch home care, nursing care and
      care homes. Data from autumn 2010 to autumn 2011 were analyzed. In total, 162
      organizations participated during this period (approximately 35% of all Dutch
      care organizations). Employee data were collected using a questionnaire (61,061
      individuals, response rate 42%). Clients were surveyed using the Client Quality
      Index for long-term care, via stratified sampling. Financial outcomes were
      collected using annual reports. SEM analyses were conducted to test the
      hypotheses. RESULTS: It was found that HR practices are - directly or indirectly 
      linked to all three outcomes. The use of HR practices is related to improved
      financial outcomes (measure: net margin), organizational outcomes (measure:
      client satisfaction) and HR outcomes (measure: sickness absence). The impact of
      HR practices on HR outcomes and organizational outcomes proved substantially
      larger than their impact on financial outcomes. Furthermore, with respect to HR
      and organizational outcomes, the hypotheses concerning the full mediating effect
      of job satisfaction are confirmed. This is in line with the view that employee
      attitudes are an important element in the 'black box' between HRM and
      performance. CONCLUSION: The results underscore the importance of HRM in the
      health care sector, especially for HR and organizational outcomes. Further
      analyses of HRM in the health care sector will prove to be a productive endeavor
      for both scholars and HR managers.

PMID- 24938462
TI  - Enhanced carrier multiplication in engineered quasi-type-II quantum dots.
AB  - One process limiting the performance of solar cells is rapid cooling
      (thermalization) of hot carriers generated by higher-energy solar photons. In
      principle, the thermalization losses can be reduced by converting the kinetic
      energy of energetic carriers into additional electron-hole pairs via carrier
      multiplication (CM). While being inefficient in bulk semiconductors this process
      is enhanced in quantum dots, although not sufficiently high to considerably boost
      the power output of practical devices. Here we demonstrate that thick-shell
      PbSe/CdSe nanostructures can show almost a fourfold increase in the CM yield over
      conventional PbSe quantum dots, accompanied by a considerable reduction of the CM
      threshold. These structures enhance a valence-band CM channel due to effective
      capture of energetic holes into long-lived shell-localized states. The attainment
      of the regime of slowed cooling responsible for CM enhancement is indicated by
      the development of shell-related emission in the visible observed simultaneously
      with infrared emission from the core. 

PMID- 24938463
TI  - Disruption of the hormonal network and the enantioselectivity of bifenthrin in
      trophoblast: maternal-fetal health risk of chiral pesticides.
AB  - Endocrine-disrupting chemicals (EDCs) can interfere with normal hormone signaling
      to increase health risks to the maternal-fetal system, yet few studies have been
      conducted on the currently used chiral EDCs. This work tested the hypothesis that
      pyrethroids could enantioselectively interfere with trophoblast cells. Cell
      viability, hormone secretion, and steroidogenesis gene expression of a widely
      used pyrethroid, bifenthrin (BF), were evaluated in vitro, and the interactions
      of BF enantiomers with estrogen receptor (ER) were predicted. At low or
      noncytotoxic concentrations, both progesterone and human chorionic gonadotropin
      secretion were induced. The expression levels of progesterone receptor and human
      leukocyte antigen G genes were significantly stimulated. The key regulators of
      the hormonal cascade, GnRH type-I and its receptor, were both upregulated. The
      expression levels of selected steroidogenic genes were also significantly
      altered. Moreover, a consistent enantioselective interference of hormone
      signaling was observed, and S-BF had greater effects than R-BF. Using molecular
      docking, the enantioselective endocrine disruption of BF was predicted to be
      partially due to enantiospecific ER binding affinity. Thus, BF could act through
      ER to enantioselectively disturb the hormonal network in trophoblast cells. These
      converging results suggest that the currently used chiral pesticides are of
      significant concern with respect to maternal-fetal health. 

PMID- 24938464
TI  - Polymorphisms in the XRCC1 gene are associated with treatment response to
      platinum chemotherapy in advanced non-small cell lung cancer patients based on
      meta-analysis.
AB  - X-ray repair cross complementing group 1(XRCC1) polymorphisms have been
      implicated in interindividual variability of efficacy of platinum chemotherapy
      for treating non-small cell lung cancer (NSCLC); however, results of different
      studies have been inconsistent. We conducted a meta-analysis to investigate the
      association between polymorphisms in the XRCC1 gene and response rate of platinum
      chemotherapy in advanced NSCLC patients. Searches were performed on MEDLINE,
      PubMed, EMBASE, Chinese Biological Medicine Database, China National Knowledge
      Infrastructure, and Wangfang Data, covering all relevant studies published up to
      August 1, 2012. Statistical analyses were performed using the Revman 5.0 and
      STATA 10.0 software. Two polymorphisms, Arg399Gln (G>A) and Arg194Trp (C>T), were
      investigated in 19 studies, involving 2152 advanced NSCLC patients. For XRCC1
      Arg399Gln, patients carrying two G alleles had a significantly increased response
      rate of platinum chemotherapy, when compared with those carrying the A allele
      [odds ratio (OR) = 2.05, 95% confidence interval CI = 1.62-2.60 for GG vs GA+AA].
      Similarly, the AA carriers had a 54% decreased response rate compared with the G
      allele carriers (OR = 0.46, 95%CI = 0.30-0.70 for AA vs GA+GG). For XRCC1
      Arg194Trp, patients carrying two C alleles had a 62% decreased response rate
      compared with those carrying either one or two variant T alleles (OR = 0.38,
      95%CI = 0.30-0.48 for CC vs CT+TT). However, although TT carriers had a better
      response rate compared with the C allele carriers, the difference was not
      significant (OR = 1.27, 95%CI = 0.92-1.77 for TT vs CC+CT). Based on this meta
      analysis, we conclude that XRCC1 polymorphisms are associated with treatment
      response to platinum chemotherapy in advanced NSCLC patients. 

PMID- 24938465
TI  - Homocysteine induces blood vessel global hypomethylation mediated by LOX-1.
AB  - Homocysteine (Hcy) is an independent risk factor of atherosclerosis through its
      involvement with the methionine cycle. In this study, we aimed to determine the
      blood vessel global methylation rate in Hcy-induced atherosclerosis in
      apolipoprotein-E-deficient (ApoE-/-) mice, and to explore the possible mechanism
      of this change in endothelial cells. ApoE-/- mice were divided into a
      hyperlipidemia (HLP) group, a hyperhomocysteinemia (HHcy) group, and an HHcy +
      folate + vitamin B12 (HHcy+FA+VB) group. Wild-type C57BL/6J mice were prepared as
      controls. Total Hcy, lipids, S-adenosylmethionine (SAM), and S
      adenosylhomocysteine (SAH) contents in serum were measured with an automatic
      biochemistry analyzer and high-performance liquid chromatography. Methylation of
      B1 repetitive elements in blood vessels was tested using nested methylation
      specific-polymerase chain reaction (nMS-PCR). Endothelial cells (ECs) were
      pretreated with Hcy or by adding FA and VB. Lectin-like oxidized LDL receptor-1
      (LOX-1) expressions were determined by quantitative PCR, Western blot, and nMS
      PCR. The HHcy group displayed severe HLP and HHcy. SAM and SAH contents were also
      elevated in the HHcy group compared with other groups. Methylation of B1
      repetitive elements was significantly increased in the HHcy group (0.5050 +/-
      0.0182) compared to the HLP (0.5158 +/- 0.0163) and control (0.5589 +/- 0.0236)
      groups. mRNA and protein expressions of LOX-1 increased (0.2877 +/- 0.0341,
      0.6090 +/- 0.0547), whereas methylation expression decreased (0.5527 +/- 0.0148)
      after 100 MUM Hcy stimulation in ECs. In conclusion, Hcy-induced atherosclerosis
      was closely associated with induced hypomethylation status in the blood vessel,
      and this process was partially mediated by LOX-1 DNA methylation. 

PMID- 24938466
TI  - Inter-retrotransposon-amplified polymorphism markers for germplasm
      characterization in Manihot esculenta (Euphorbiaceae).
AB  - Manioc, Manihot esculenta, is economically important in many tropical and
      subtropical countries. The genetic variability of the species has not been fully
      explored, and new information may help expand its use. Molecular markers based on
      retrotransposons have good potential for analysis of genetic diversity given
      their abundance in the genome. Eight long terminal repeat retrotransposons were
      selected for the development of inter-retrotransposon-amplified polymorphism
      markers. To test these primers, we analyzed 32 varieties from Anori, 30 from
      Manicore and 10 Mandiocabas from the Manioc Germplasm Bank at Embrapa Western
      Amazonia. The six informative primer pairs yielded 20- 60 polymorphic bands,
      averaging 92% polymorphism (51.7-98.4) and 0.37 heterozygosity (0.17 to 0.40),
      with a Shannon information index of 0.54 (0.26-0.59). These markers can be used
      to explore the genetic diversity of manioc. 

PMID- 24938467
TI  - Genetic variants of the endothelial NO synthase gene (eNOS) may confer increased
      risk of sporadic congenital heart disease.
AB  - The endothelial NO synthase (eNOS) enzyme is expressed during the early stages of
      cardiogenesis and plays an important role in normal heart development. Genetic
      variations of eNOS G894T have been shown to influence individual susceptibility
      to some phenotypes of congenital heart disease (CHD) in different populations. We
      conducted a case-control study comprised of 945 CHD patients and 972 non-CHD
      individuals in a Chinese population. Two functional single nucleotide
      polymorphisms (SNPs) (T-786C: rs2070744 and G894T: rs1799983) and one tagging SNP
      (rs7830) were evaluated in our study, and we assessed their association with the
      risk of CHD. Compared with the rs7830 CC/AC genotypes, the eNOS rs7830 AA
      genotype showed a significantly increased risk of CHD (adjusted odds radio (OR) =
      1.45, 95% confidence interval (CI = 1.13-1.85). A stratified analysis was
      performed and showed that the association between the rs7830 AA genotype and CHD
      risk was stronger in patients with perimembranous ventricular septal defects
      (adjusted OR = 1.62, 95%CI = 1.20-2.20). Our results suggest that the eNOS rs7830
      polymorphism may contribute to the susceptibility of sporadic CHD in a Chinese
      population. 

PMID- 24938468
TI  - Implication of polymorphisms in DNA repair genes with an increased risk of
      hepatocellular carcinoma.
AB  - We explored the association between 4 XRCC1 (Arg194Trp and Arg399Gln) and XPD
      (Asp312Asn and Lys751Gln) polymorphisms with the development and prognosis of
      hepatocellular carcinoma (HCC). A total of 218 cases with HCC and 277 healthy
      controls were included in the study. Genotyping of the XRCC1 (Arg194Trp and
      Arg399Gln) and XPD (Asp312Asn and Lys751Gln) polymorphisms was performed in a 384
      well plate format on the Sequenom MassARRAY platform. We found that individuals
      with the XRCC1 399AA genotype had a higher risk of HCC compared with the GG
      genotype (odds ratio, OR = 1.85, 95% confidence interval, CI = 1.03-3.23).
      Similarly, individuals carrying the XPD 751GG genotype showed a greatly increased
      risk of HCC (OR = 2.97, 95%CI = 126- 7.38). Cox regression analysis showed that
      individuals carrying XPD 751Gln/Gln genotypes had a 0.30-fold increased risk of
      death from HCC. These results suggest that polymorphisms in XRCC1 and XPD may
      have functional significance in HCC. 

PMID- 24938469
TI  - High-sensitivity cardiac troponin T is a predictor of recurrent acute coronary
      syndrome in patients with acute myocardial infarction.
AB  - High-sensitivity cardiac troponin T is a useful tool for diagnosing myocardial
      ischemia. However, its role in the prognosis of patients with acute myocardial
      infarction has not been studied. Here, the prognostic value of high-sensitivity
      cardiac troponin T for patients with acute myocardial infarction was
      investigated. The concentrations of high-sensitivity cardiac troponin T, other
      clinical chemistry makers, and living habits were investigated at the time of
      admission in patients with acute coronary syndrome, whereas the high-sensitivity
      cardiac troponin T concentrations at 6 h after admission and during recovery were
      analyzed in other patient groups. The concentration of high-sensitivity cardiac
      troponin T was significantly higher in patients with acute myocardial infarction
      than in those with other cardiac diseases and in controls (P < 0.01). Based on
      the standard diagnostic criterion, 134 patients were diagnosed with acute
      myocardial infarction. Monitoring the change in concentration of high-sensitivity
      cardiac troponin T in patients with acute coronary syndrome can reduce the risk
      of recurrence and death. 

PMID- 24938470
TI  - Association of polymorphisms of the xeroderma pigmentosum complementation group F
      gene with increased glioma risk.
AB  - We aimed to investigate the role of 4 single nucleotide polymorphisms of the
      xeroderma pigmentosum complementation group F (XPF) gene (rs3136038, rs1799798,
      rs1800067, and rs2276466) in glioma, and the roles of gene-gene interactions in
      the risk of developing this type of cancer. We collected samples from 225 glioma
      cases and 262 controls and genotyped the rs3136038, rs1799798, rs1800067, and
      rs2276466 polymorphisms using a 384-well plate format with the Sequenom MassARRAY
      platform. Individuals carrying the rs1800067 GG genotype were more likely to have
      an increased risk of glioma when compared with carriers of the A/A genotype in a
      co-dominant model, with an odds ratio (OR) [95% confidence interval (CI)] of 2.85
      (1.14-7.76). However, we did not find an association with increased risk of
      glioma for the polymorphisms rs3136038, rs1799798, and rs2276466 in XPF. The
      combination genotype of the rs1800067 G allele and the rs2276466 G allele was
      associated with a moderate risk of glioma (OR = 1.71, 95%CI = 1.02-2.87). Our
      study suggests that the rs1800067 genetic variant of XPF functions in the
      development of glioma. 

PMID- 24938471
TI  - Effect of RNAi-mediated silencing of Livin gene on biological properties of colon
      cancer cell line LoVo.
AB  - This study aimed to investigate the effect of RNAi-mediated silencing of the
      Livin gene on biological properties of the colon cancer cell line LoVo.
      Interference vectors pSilencer4.1-Ll and pSilencer4.1-L2 targeting the Livin gene
      were constructed and transfected into LoVo cells. The expression of the Livin
      gene was determined by RT-PCR and Western blotting. The apoptosis, cell cycle,
      colony formation, proliferation of LoVo cells, as well as their sensitivity to
      cisplatin, were detected by flow cytometry, colony formation assay and MTT. Livin
      mRNA and protein expression in LoVo cells could be effectively silenced by
      pSilencer4.1-Ll but not pSilencer4.1-L2. In the pSilencer4.1-Ll transfection
      group, the apoptosis rate of LoVo cells was significantly higher than in the
      control group (24.2 +/- 3.2 vs 8.1 +/- 1.4%, P < 0.01), and after 72 h, cell
      proliferation was clearly decreased (about 70% inhibition). Compared with the
      control group, the colony formation rate in pSilencer4.1-Ll transfection group
      was obviously decreased (15 +/- 4.6 vs 85 +/- 5.8%, P < 0.01), with increased
      proportion of S phase cells (45.7 +/- 4.9 vs 28.0 +/- 3.0%, P < 0.01), decreased
      proportion of G1 phase cells (43.0 +/- 5.2 vs 62.8 +/- 5.1%, P < 0.01), and
      increased sensitivity to cisplatin (apoptosis rate increased from 43.4 +/- 6.9 to
      65.3 +/- 6.2%, P < 0.01). pSilencer4.1-Ll can effectively silence Livin gene
      expression in LoVo colon cancer cells, inhibit cell proliferation and colony
      formation, induce apoptosis, and enhance sensitivity to cisplatin. 

PMID- 24938472
TI  - Multidrug-resistant genes of aminoglycoside-modifying enzymes and 16S rRNA
      methylases in Acinetobacter baumannii strains.
AB  - We examined the distribution of genes of aminoglycoside-modifying enzymes and 16S
      rRNA methylases in multidrug-resistant Acinetobacter baumannii to explore the
      association of these genes with drug resistance. Strains isolated from clinical
      specimens were screened using an automatic microbial identification system, and 9
      aminoglycoside-modifying enzyme and 6 16S rRNA methylase genes were analyzed
      using polymerase chain reaction and verified by DNA sequencing. Next, sequence
      alignment was carried out using the Chromas software and a susceptibility test
      was performed using the Kirby-Bauer disk diffusion method. Genes encoding
      aminoglycoside-modifying enzymes were detected in all 20 strains of multidrug
      resistant A. baumannii. The positive rates of aac(3')-I, aac(6')-Ib, ant(3'')-I,
      and aph(3')-I were 90.0, 90.0, 85.0, and 35.0%, respectively. However, genes
      encoding 16S rRNA methylases were not positively detected in the 20 strains of
      multidrug-resistant A. baumannii. The resistance of multidrug-resistant A.
      baumannii may be associated with aminoglycoside-modifying enzyme genes but not
      with 16S rRNA methylase genes. 

PMID- 24938473
TI  - Expression and enzymatic activity of phenylalanine ammonia-lyase and p-coumarate
      3-hydroxylase in mango (Mangifera indica 'Ataulfo') during ripening.
AB  - Phenylalanine ammonia lyase (PAL) and p-coumarate 3-hydroxylase (C3H) are key
      enzymes in the phenylpropanoid pathway. The relative expression of PAL and C3H
      was evaluated in mango fruit cultivar 'Ataulfo' in four ripening stages (RS1,
      RS2, RS3, and RS4) by quantitative polymerase chain reaction. In addition, enzyme
      activity of PAL and C3H was determined in mango fruits during ripening. The PAL
      levels were downregulated at the RS2 and RS3 stages, while C3H levels were
      upregulated in fruits only at RS3. The enzyme activity of PAL followed a pattern
      that was different from that of the PAL expression, thus suggesting regulation at
      several levels. For C3H, a regulation at the transcriptional level is suggested
      because a similar pattern was revealed by its activity and transcript level. In
      this study, the complexity of secondary metabolite biosynthesis regulation is
      emphasized because PAL and C3H enzymes are involved in the biosynthesis of
      several secondary metabolites that are active during all mango ripening stages. 

PMID- 24938474
TI  - Olfactory mucosal microstructural changes in a rat model of acute rhinosinusitis
      with dysosmia.
AB  - This study aimed to examine olfactory mucosal changes in a rat model of acute
      rhinosinusitis and to determine how acute rhinosinusitis induces dysosmia. Total
      100 rats were divided into the experimental (N = 80) and control (N = 20) groups.
      An acute rhinosinusitis model was established in the experimental rats. From the
      experimental group, 20 rats each were sacrificed at 1, 2, 3, or 4 weeks. The
      control group was sacrificed at 1 week without inoculation. Olfaction was tested
      by the buried food pellet test before killing the rats, and the duration until
      the pellet was recorded and analyzed by a statistical software program. Mature
      olfactory receptor neurons (ORNs) and olfactory ensheathing cells (OECs) were
      examined. The durations spent by the experimental group in the BFPT were 402.9 +/
      9.3, 453.7 +/- 7.3, 351.9 +/- 8.9, and 278.7 +/- 8.1 s at 1, 2, 3, and 4 weeks,
      respectively. These durations were greater than that of the control group (178.3
      +/- 6.6 s), and the difference was statistically significant (P < 0.01). A
      reduction in ORNs and thinning of the epithelium were detected in the
      experimental group, most notably in the 2nd week and less in the fourth week.
      OECs were reduced in the 1st week, increased in the 2nd week, and almost
      completely recovered in the fourth week. In addition, some growing OECs were
      detected in the experimental group. Acute rhinosinusitis decreased both the
      mature ORNs and OECs, but OECs increased faster than the ORNs. 

PMID- 24938476
TI  - Assessment of adolescent mental health and behavioral problems in institutional
      care: discrepancies between staff-reported CBCL scores and adolescent-reported
      YSR scores.
AB  - For children residing in institutional settings, staff act as primary caregivers
      and often provide assessment of child psychopathology. Minimal research exists on
      how and when staff-caregivers are best positioned to report on youth mental
      health. This study examines differences between 60 staff-reported and 60
      adolescent-reported Child Behavioral Checklist/Youth Self-Report (CBCL/YSR)
      scores in Jordanian care centers, and the associations between adolescent-staff
      agreement, demographic characteristics and child-caregiver relationship factors.
      Results indicated small to modest correlations between informant scores.
      Additionally, staff-caregivers who know the child over 1 year and have a high
      perceived fit are better able to approximate the adolescent's self-report of
      psychopathology.

PMID- 24938475
TI  - A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA
      encoding a tumor-specific chimeric antigen receptor.
AB  - Chimeric antigen receptors (CARs), which combine an antibody-derived binding
      domain (single chain fragment variable) with T-cell-activating signaling domains,
      have become a promising tool in the adoptive cellular therapy of cancer. Retro-
      and lenti-viral transductions are currently the standard methods to equip T cells
      with a CAR; permanent CAR expression, however, harbors several risks like
      uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR
      encoding RNA to achieve transient expression likely circumvents these
      difficulties. We here present a GMP-compliant protocol to activate and expand T
      cells for clinical application. The protocol is optimized in particular to
      produce CAR-modified T cells in clinically sufficient numbers under full GMP
      compliance from late-stage cancer patients. This protocol allows the generation
      of 6.7 * 10(8) CAR-expressing T cells from one patient leukapheresis. The CAR
      engineered T cells produced pro-inflammatory cytokines after stimulation with
      antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner.
      This functional capacity was maintained after cryopreservation. Taken together,
      we provide a clinically applicable protocol to transiently engineer sufficient
      numbers of antigen-specific patient T cells for use in adoptive cell therapy of
      cancer.

PMID- 24938477
TI  - Fibre-induced feed sorting in King Quail (Coturnix chinensis): behavioural
      plasticity elicited by a physiological challenge.
AB  - We examined the effect of an abrupt change in diet fibre content on the feed
      intake, gastrointestinal morphology and utilisation of gastroliths by a small
      (ca. 40 g body mass) herbivorous bird, the King Quail (Coturnix chinensis). King
      Quail were acclimated for 14 days on a low-fibre (LF) pullet starter diet.
      Following acclimation, half the quail population was immediately switched to a
      23% wood-shaving diluted high-fibre (HF) diet for a further 14 days. Contrary to
      expectations, we found no differences in feed intake, gut morphology or
      gastrolith mass between the LF- and HF-fed quail. However, when switched from the
      LF to HF diet, the quail commenced feed-sorting behaviours that permitted HF-fed
      animals to maintain body condition (mass, abdominal fat mass) without adjustments
      to intestinal organ sizes or gastrolith mass. Feed sorting was initiated only
      after exposure to the HF diet, which corresponded with an immediate reduction in
      food intake, suggesting that the sorting behaviour was cued by a physiological
      challenge associated with the HF diet. This challenge apparently induced
      preferential sorting behaviour and was possibly due to abrupt changes in the rate
      of food passage, impacting satiation or other internal cues.

PMID- 24938478
TI  - Fabrication of well-ordered binary colloidal crystals with extended size ratios
      for broadband reflectance.
AB  - Binary colloidal crystals (BCCs) possess great potentials in tuning material
      properties by controlling the size ratio of small to large colloidal spheres
      (gammaS/L). In this paper, we present a method for the fabrication of BCCs with
      much more extended size ratios than those obtained in conventional convective
      self-assembly method. It is found that gammaS/L can be extended to 0.376 by
      adding TEOS sol into the colloidal suspension. The resulting polystyrene/silica
      (PS/SiO2) BCCs show distinctive reflections, indicating their well-ordered
      structure. The extended size ratios render more flexibility in engineering the
      photonic bandgap structures of BCCs and hence provide a better platform for
      developing a range of applications such as photonics, spintronics, sensing and
      bioseparation. 

PMID- 24938479
TI  - The hexosamine biosynthesis pathway and O-GlcNAcylation maintain insulin
      stimulated PI3K-PKB phosphorylation and tumour cell growth after short-term
      glucose deprivation.
AB  - Glucose provides an essential nutrient source that supports glycolysis and the
      hexosamine biosynthesis pathway (HBP) to maintain tumour cell growth and
      survival. Here we investigated if short-term glucose deprivation specifically
      modulates the phosphatidylinositol 3-kinase/protein kinase B (PI3K/PKB) cell
      survival pathway. Insulin-stimulated PKB activation was strongly abrogated in the
      absence of extracellular glucose as a consequence of the loss of insulin
      stimulated PI3K activation and short-term glucose deprivation inhibited
      subsequent tumour cell growth. Loss of insulin-stimulated PKB signalling and cell
      growth was rescued by extracellular glucosamine and increased flux through the
      HBP. Disruption of O-GlcNAc transferase activity, a terminal step in the HBP,
      implicated O-GlcNAcylation in PKB signalling and cell growth. Glycogenolysis is
      known to support cell survival during glucose deprivation, and in A549 lung
      cancer cells its inhibition attenuates PKB activation which is rescued by
      increased flux through the HBP. Our studies show that rerouting of glycolytic
      metabolites to the HBP under glucose-restricted conditions maintains PI3K/PKB
      signalling enabling cell survival and proliferation. 

PMID- 24938480
TI  - Longitudinal patterns of problematic computer game use among adolescents and
      adults--a 2-year panel study.
AB  - AIMS: To investigate the longitudinal patterns (stability and change) of
      problematic computer game use and its interdependencies with psychosocial
      wellbeing in different age groups. DESIGN: Three-wave, annual panel study using
      computer-assisted telephone surveys. SETTING: Germany. PARTICIPANTS: A total of
      112 adolescents aged between 14 and 18 years, 363 younger adults between 19-39
      years and 427 adults aged 40 years and older (overall n = 902). MEASUREMENTS:
      Problematic game use was measured with the Gaming Addiction Short Scale (GAS),
      which covers seven criteria including salience, withdrawal and conflict.
      Additionally, gaming behaviour and psychosocial wellbeing (social capital and
      support, life satisfaction and success) were measured in all three panel waves.
      FINDINGS: The generally low GAS scores were very stable in yearly intervals
      [average autocorrelation across waves and age groups: r = 0.74, confidence
      interval (CI) = 0.71, 0.77]. Only nine respondents (1%, CI = 0.5, 1.9)
      consistently exhibited symptoms of problematic game use across all waves, while
      no respondent could be classified consistently as being addicted according to the
      GAS criteria. Changes in problematic gaming were not related consistently to
      changes in psychosocial wellbeing, although some cross-lagged effects were
      statistically significant in younger and older adult groups. CONCLUSIONS: Within
      a 2-year time-frame, problematic use of computer games appears to be a less
      stable behaviour than reported previously and not related systematically to
      negative changes in the gamers' lives.

PMID- 24938481
TI  - Psychomotor development following early treatment of severe infantile vitamin B12
      deficiency and West syndrome--is everything fine? A case report and review of
      literature.
AB  - BACKGROUND: Severe infantile vitamin B12 deficiency is occasionally reported in
      developed countries due to maternal nutritional deficiency. The clinical
      manifestation comprises megaloblastic anemia and neurodevelopmental delay
      culminating in demyelination and brain atrophy. Few case reports have documented
      manifestation of West syndrome. PATIENT: We report the 8-year long-term follow-up
      on a 6-month-old exclusively breast-fed girl with serious vitamin B12 deficiency
      secondary to undiagnosed maternal pernicious anemia. MRI revealed cerebral
      atrophy and delayed myelination. Strikingly, initial vitamin B12-mediated
      improvement of neurological and hematological findings was followed by temporary
      manifestation of infantile spasms requiring anticonvulsive therapy. RESULTS:
      Seizures soon dissolved, EEG and MRI scan normalized and developmental catch-up
      occurred. At the age of 8 years, the girl is symptom-free and visits primary
      school illustrating remarkable recovery of severe neurodevelopmental delay and
      symptomatic West syndrome. CONCLUSION: Infantile vitamin B12 deficiency has to be
      considered in the differential diagnosis of mental retardation and infantile
      spasms, especially if maternal nutritional deficiency might be suspected. Early
      treatment seems to be crucial for the prevention of irreversible brain damage.

PMID- 24938482
TI  - Single-nucleotide polymorphisms and reading frame shifts in RNA2 recombinant
      regions of tobacco rattle virus isolates Slu24 and Deb57.
AB  - Two previously sequenced tobacco rattle virus (TRV) isolates, Slu24 and Deb57,
      from Polish potato fields have recombinant RNA2 species. The 3'-proximal region
      of the Slu24 RNA2 is derived from the 3' terminus of its supporting RNA1, while
      that of the Deb57 RNA2 is derived from the 3' terminus of the unrelated RNA1 from
      the isolate SYM or PpK20. Gene structure annotation revealed open reading frames
      encoding truncated 16-kDa proteins in the recombinant regions of the RNA2 of
      Deb57 and Slu24. Reading frame shifts, single nucleotide substitutions and
      deletions occurred during recombination, including shifts from a stop codon or
      replacements of an internal stop codon. In the recombinant region of the Deb57
      RNA2, the first reading frameshift event starts from the AUG start codon of the
      truncated 16-kDa protein. The second frameshift event, caused by a single
      nucleotide deletion upstream of the stop codon, leads to the splitting of the
      stop codon into two amino acid codons and the continuation of translation. In
      addition, a U-to-A substitution changes a potential internal stop codon UAA,
      which is caused by recombination-related frame shifts, into the codon AAA,
      encoding lysine. The replacement of this internal stop codon with an amino acid
      codon prevented the premature translation termination of the truncated 16-kDa
      protein. These recombination-related reading frame shifts are the driving force
      underlying the major differences in the translated amino acids, consequently
      leading to their translation into distinct polypeptides. Conversely, single
      nucleotide substitutions in the recombinant regions of the RNA2 of Deb57 or Slu24
      resulted in only minor changes in the translated amino acids.

PMID- 24938483
TI  - Experimental infection of cattle and goats with a foot-and-mouth disease virus
      isolate from the 2010 epidemic in Japan.
AB  - In this study, we carried out experimental infections in cattle and goats using a
      foot-and-mouth disease virus (FMDV) isolate from the 2010 epidemic in Japan to
      analyze clinical manifestations, virus-shedding patterns and antibody responses
      in the animals. We found that the FMDV O/JPN/2010 isolate is virulent in cattle
      and goats, produces clinical signs, is spread efficiently by direct contact
      within the same species, and is persistently infectious in cattle. Quantitative
      analysis of levels of viral RNA in the tissues of cattle and goats infected with
      the isolate showed that the pharyngeal region is an important major target of the
      FMDV O/JPN/2010. Time course data of viral loads, excretion and transmission of
      the FMDV O/JPN/2010 in this study are key in providing quantitative data
      essential for epidemiological investigation and risk analysis in relation to
      disease controls. 

PMID- 24938484
TI  - Simultaneous detection of groundnut rosette assistor virus (GRAV), groundnut
      rosette virus (GRV) and satellite RNA (satRNA) in groundnuts using multiplex RT
      PCR.
AB  - Groundnut rosette disease (GRD) is the most devastating disease of groundnuts in
      sub-Saharan Africa. The disease is caused by synergistic interactions between
      viruses and virus-like pathogens: groundnut rosette assistor virus (GRAV),
      groundnut rosette virus (GRV) and a satellite RNA (satRNA). The multi-pathogenic
      nature of GRD requires efficient diagnostic systems for plant breeding and
      pathology work. Currently, TAS-ELISA and RT-PCR are used to detect all three
      pathogens. This approach is time-consuming, expensive and not easily amenable to
      high throughput. A multiplex PCR-based approach was developed to detect all three
      pathogens at once, reducing diagnostics costs and time by two thirds. The
      technique is highly robust and amenable to high throughput, with sensitivity and
      specificity values of 88 % and 100 %, respectively. The positive predictive value
      for the technique is 100 %, and the negative predictive value is 90.6 %.

PMID- 24938485
TI  - Complete genome sequence of enterobacteria phage 4MG, a new member of the
      subgroup "PVP-SE1-like phage" of the "rV5-like viruses".
AB  - A novel virulent enterobacteria phage, 4MG, which was isolated from soil near a
      sewer, belongs to the family Myoviridae, as it possesses an isometric head and a
      long contractile tail. The complete genome of 4MG consists of a double-stranded
      DNA with a length of 148,567 bp, a G + C content of 46.3 %, 271 open reading
      frames (ORFs), and 21 tRNAs. Bioinformatic analysis revealed that 4MG highly
      resembles "rV5-like viruses" but can be separated, together with Salmonella phage
      PVP-SE1 and Cronobacter sakazakii phage vB_CsaM_GAP31, as part of the subgroup
      "PVP-SE1-like phage".

PMID- 24938486
TI  - Detection and sequence analysis of two novel co-infecting double-strand RNA
      mycoviruses in Ustilaginoidea virens.
AB  - Four novel double-stranded RNA molecules, named dsRNA 1 (5124 bp), dsRNA 2(1711
      bp), dsRNA 3 (1423 bp) and dsRNA 4 (855 bp), were detected in strain HNHS-1 of
      Ustilaginoidea virens, the causal agent of rice false smut disease. Sequence
      analysis showed that the dsRNA1 contains two overlapping open reading frames
      (ORF) potentially encoding proteins with modest levels of sequence similarity to
      the coat protein (CP) and putative RNA-dependent RNA polymerase (RdRp),
      respectively, of viruses of the family Totiviridae. The deduced gene product of
      the ORF encoded by dsRNA2 is homologous to putative RdRp of viruses in the family
      Partitiviridae; the ORF encoded by dsRNA3 shares some similarity to a
      hypothetical protein with unknown function. It is noteworthy that the dsRNA4
      lacked integrated ORFs. Isomeric viral particles of about 40 nm in diameter were
      observed by transmission electron microscopy in a mycelium tissue preparation of
      strain HNHS-1-R1, a single-spore subculture of strain HNHS-1 containing only the
      dsRNA1 segment. Phylogenetic analysis and examination of the organization of the
      two putative RdRp sequences both indicated that there are at least two novel
      virus species present in strain HNHS-1. We named the two novel viruses
      Ustilaginoidea virens RNA virus 2 and Ustilaginoidea virens partitivirus 4,
      respectively.

PMID- 24938487
TI  - First report of isolation and molecular characterization of bubaline herpesvirus
      1 (BuHV1) from Argentinean water buffaloes.
AB  - Herpesviruses have mainly co-evolved with their hosts for millions of years.
      However, bovine herpesvirus 1 (BoHV1) and related ruminant alphaherpesviruses
      have been reported to cross the species barrier. Bubaline herpesvirus 1 (BuHV1)
      is an alphaherpesvirus closely related to BoHV1 and BoHV5. According to the
      serological cross-relationships between ruminant alphaherpesviruses, several
      surveys have studied the occurrence of BoHV1-related virus infection in wild and
      domestic ruminant species. Recent studies in Argentina showed an increase in
      serological prevalence against BoHV1 related viruses in water buffaloes (Bubalus
      bubalis) population. The aim of this study was to investigate the presence of
      related ruminant alphaherpesvirus in the Argentinean water buffalo population.
      BuHV1 was successfully isolated from 5 out of 225 buffaloes analyzed. One isolate
      was obtained from nasal secretions, and the others were from vaginal swabs. The
      buffaloes belonged to four different farms located in northeastern Argentina. The
      isolates were characterized as alphaherpesvirus by direct immunofluorescence
      using FITC-anti-BoHV1 IgG. Restriction analysis performed with BamHI and BstEII
      on the complete genome showed differences between the isolates and those from
      BoHV1 and BoHV5 subtypes. Phylogenetic analysis on both UL27 and US6 showed
      similarity in tree topology. While three of the isolates grouped together with
      sequences of BoHV5, two other isolates clustered separately. Genetic analysis of
      eight concatenated sequences from all isolates and references strains showed high
      nucleotide sequence identity between BuHV1 and BoHV5. While three of the isolates
      clustered together with the BoHV5 reference strain, the last two isolates were
      closely related to an Australian BuHV1 strain. To our knowledge, this is the
      first report on the isolation and molecular characterization of BuHV1 in South
      America. Phylogenetic analysis suggested that two different BuHV1 lineages
      circulate in the Argentinean water buffalo population.

PMID- 24938488
TI  - Urgineaglyceride A: a new monoacylglycerol from the Egyptian Drimia maritima
      bulbs.
AB  - One new compound, (2S)-1-O-(Z)-tetracos-6-enoate glycerol (1) named
      urgineaglyceride A, along with six known compounds, 3,5,7,3',5'
      pentahydroxydihydroflavonol (2), stigmasterol (3), (25S)-5beta-furostane-3beta
      22alpha-26-triol (4), scillaridin A (5), (2S)-(+)-2-hydroxynaringenin-4'-O-beta-D
      glucopyranoside (6) and quercetin-3'-O-beta-D-glucopyranoside (7), were isolated
      from the EtOAc fraction of Drimia maritima (L.) Stearn bulbs. Their structures
      were secured based on their IR, UV, 1D and 2D NMR data, in addition to HR-MS data
      and comparison with the literature data. The isolated compounds were evaluated
      for their in vitro growth inhibitory activity against A549 non-small cell lung
      cancer (NSCLC), U373 glioblastoma (GBM) and PC-3 prostate cancer cell lines.
      Compounds 2 and 3 displayed variable activities against the tested cancer cell
      lines. Compound 2 was a selective inhibitor of the NSCLC cell line with an IC50
      of 2.3 MUM, whereas 3 was selective against GBM with IC50 of 0.5 MUM and against
      PC-3 with 2.0 MUM.

PMID- 24938489
TI  - Automated synthesis of backbone protected peptides.
AB  - The synthesis of peptides rich in aggregation prone sequences can be improved
      with backbone protection. We report the automated introduction of backbone
      protection to a peptide. This new method was applied in a fully-automated
      synthesis, giving improved handling, quality and yield of several challenging
      target sequences. 

PMID- 24938490
TI  - Efficient one-pair experimental system for spatial resolution demonstration of
      prototype PET detectors.
AB  - In the development of depth-of-interaction (DOI)-positron emission tomography
      (PET) detectors, one of the important steps toward their practical use is an
      evaluation of their imaging performance, such as the spatial resolution as
      measured by use of a point source and a one-pair experimental system which
      simulates actual PET geometries. The DOI-PET detectors have a broad field of view
      providing good imaging performance compared with conventional detectors.
      Therefore, evaluation including the region from the center to the periphery close
      to the detector ring is required in an effort to show their advanced performance
      regarding uniform spatial resolution. In this study, we aimed to develop and
      evaluate an efficient one-pair experimental system for demonstration of the DOI
      PET detector performance. For this purpose, we propose a one-pair experimental
      system that can simulate an arbitrary ring diameter and acquire projection data
      efficiently by skipping unnecessary combinations according to the position of the
      point source. As a result, the proposed system and our measuring scheme could
      significantly reduce the total measurement time, especially for a large ring size
      such as that used in brain PET scanners and whole-body PET scanners. We used the
      system to evaluate the X'tal cube PET detector with a 2-mm cubic crystal array
      arranged in simulated PET geometries with ring diameters of 8.2 and 14.6 cm for
      12 and 18 detector blocks, respectively. The results showed that a uniform
      spatial resolution was achieved even in the peripheral region, and measurements
      were obtained semi-automatically in a short time.

PMID- 24938491
TI  - Colon and rectal cancer incidence and water trihalomethane concentrations in New
      South Wales, Australia.
AB  - BACKGROUND: There is evidence, although inconsistent, that long term exposure to
      disinfection by products (DBPs) increases the risk of bowel cancer. No study has
      been conducted in Australia to examine this association and due to difference in
      the methods of disinfection the risk can vary across geographical regions and.
      This study was conducted to analyse the association of trihalomethanes (THMs) in
      water with colon and rectal cancer in NSW Australia. METHODS: Average yearly
      concentrations of total and individual species of THMs were obtained for 50 local
      government areas (LGAs). Indirectly-standardized incidence rates of colon and
      rectal cancers in LGAs for the period 1995 to 2001 were regressed against mean
      THM concentrations lagged five years, adjusting for socioeconomic status, high
      risk drinking, smoking status, usual source of water and year of diagnosis,
      including local and global random effects within a Bayesian framework. The
      incidence rate ratios (IRRs) for an interquartile range (IQR) increase in THMs
      were estimated. RESULTS: Using five year lag of exposure there was a positive
      association between bromoform concentration and CRC in men (IRR = 1.025, 95% CI
      1.010, 1.040) but not in women (IRR = 1.003, 95% CI 0.987, 1.018). The
      association in men was mainly found in colon cancer with bromoform (IRR = 1.035,
      95% CI 1.017, 1.053). There was no appreciable association of colorectal cancer
      with other species of THMs. Sensitivity analyses did not materially change the
      associations observed. CONCLUSION: A positive association was observed between
      colon cancer and water bromoform concentrations in men. Given the potential
      population impact of such an association, further research into the relationship
      between THMs, particularly brominated species, and colorectal cancer is
      warranted.

PMID- 24938492
TI  - Aligning everyday life priorities with people's self-management support networks:
      an exploration of the work and implementation of a needs-led telephone support
      system.
AB  - BACKGROUND: Recent initiatives to target the personal, social and clinical needs
      of people with long-term health conditions have had limited impact within primary
      care. Evidence of the importance of social networks to support people with long
      term conditions points to the need for self-management approaches which align
      personal circumstances with valued activities. The Patient-Led Assessment for
      Network Support (PLANS) intervention is a needs-led assessment for patients to
      prioritise their health and social needs and provide access to local community
      services and activities. Exploring the work and practices of patients and
      telephone workers are important for understanding and evaluating the workability
      and implementation of new interventions. METHODS: Qualitative methods
      (interviews, focus group, observations) were used to explore the experience of
      PLANS from the perspectives of participants and the telephone support workers who
      delivered it (as part of an RCT) and the reasons why the intervention worked or
      not. Normalisation Process Theory (NPT) was used as a sensitising tool to
      evaluate: the relevance of PLANS to patients (coherence); the processes of
      engagement (cognitive participation); the work done for PLANS to happen
      (collective action); the perceived benefits and costs of PLANS (reflexive
      monitoring). 20 patients in the intervention arm of a clinical trial were
      interviewed and their telephone support calls were recorded and a focus group
      with 3 telephone support workers was conducted. RESULTS: Analysis of the
      interviews, support calls and focus group identified three themes in relation to
      the delivery and experience of PLANS. These are: formulation of 'health' in the
      context of everyday life; trajectories and tipping points: disrupting everyday
      routines; precarious trust in networks. The relevance of these themes are
      considered using NPT constructs in terms of the work that is entailed in engaging
      with PLANS, taking action, and who is implicated this process. CONCLUSIONS: PLANS
      gives scope to align long-term condition management to everyday life priorities
      and valued aspects of life. This approach can improve engagement with health
      relevant practices by situating them within everyday contexts. This has potential
      to increase utilisation of local resources with potential cost-saving benefits
      for the NHS. TRIAL REGISTRATION: ISRCTN45433299.

PMID- 24938493
TI  - The social determinants of health for people with type 1 diabetes that progress
      to end-stage renal disease.
AB  - OBJECTIVE: Self-management of type 1 diabetes over a lifetime is complex and
      challenging even in the best of circumstances, and the social environment can be
      a powerful determinant of health behaviours and outcomes. The aim of this study
      was to identify how social determinants of health can impact on the capacity of
      young people to manage their glycaemic control. METHODS: The findings emerged
      from a constructivist grounded theory approach through an in-depth examination of
      life course events that were recounted through qualitative interviews. The rich
      descriptive detail obtained from this enquiry locates common experiences and the
      context in which concordance with therapies occurs and health behaviours develop.
      RESULTS: This qualitative study of young people with type 1 diabetes who have
      developed end-stage renal disease demonstrates that there are many factors beyond
      individual control that can contribute to health outcomes. The social
      determinants of childhood environment, education, socio-economic status, gender
      and the culture of public health can contribute to disengagement from treatment
      regimens and the health-care system and to the development of microvascular
      complications at a comparatively young age. CONCLUSION: These findings challenge
      the assumptions of health-care practitioners about individual responsibility and
      highlight the importance of considering how social determinants can shape lives,
      behaviours and health.

PMID- 24938494
TI  - Prevalence, patterns and correlates of alcohol consumption and its' association
      with tobacco smoking among Sri Lankan adults: a cross-sectional study.
AB  - BACKGROUND: Most studies on alcohol consumption carried out in Sri Lanka are
      limited to single/few provinces in the island. The objective of this study was to
      determine the prevalence, patterns and correlates of alcohol consumption among a
      larger sample of adults in Sri Lanka. METHODS: This cross-sectional study was
      conducted in seven of all nine provinces in Sri Lanka, between 2005 and 2006. A
      nationally representative sample of 5000 adults aged >=18 years was selected
      using multi-stage random cluster sampling. Data of 4532 participants were
      collected using an interviewer administered questionnaire. Data analysis included
      chi-squared test, multiple logistic regression analysis and Spearman correlation
      using Stata/SE 10.0 (StataCorp LP., Texas, USA) software package. RESULTS: Males
      were 40%; mean age was 46.1 years (+/-15.1). The overall, urban and rural
      prevalence (95% CI) of current drinking was 23.7% (21.7 - 25.7), 29.5% (25.7 -
      33.3) and 22.2% (19.8 - 24.7) respectively (p = 0.001). Current (M: 48.1%, F:
      1.2%, p < 0.0001) and former (M: 21.4%, F: 0.7%, p < 0.0001) drinking was much
      higher in males. The highest prevalence of drinking in males (58.9%) and females
      (2.2%) was in the 30 - 39 and <20 year age groups respectively. Lowest prevalence
      in men (24.6%) and women (0%) was in the >70 years age-group. Hazardous drinking
      was seen in 5.2% of men and 0.02% of women. Male sex, urban living and current
      smoking correlated with both current and hazardous drinking. Lower level of
      education, and age >70 years positively correlated with hazardous drinking.
      CONCLUSIONS: Alcohol is predominantly a problem in Sri Lankan males. In males,
      both current and hazardous drinking positively correlated with urban living,
      white collar occupation, Burgher ethnicity and current smoking. Hazardous
      drinking positively correlated with lower level of education and older age. The
      data shown here are useful in planning interventions simultaneously targeting
      alcohol and tobacco.

PMID- 24938495
TI  - Pharmacological evaluation and docking studies of alpha,beta-unsaturated carbonyl
      based synthetic compounds as inhibitors of secretory phospholipase A2,
      cyclooxygenases, lipoxygenase and proinflammatory cytokines.
AB  - Arachidonic acid and its metabolites have generated high level of interest among
      researchers due to their vital role in inflammation. The inhibition of enzymes
      involved in arachidonic acid metabolism has been considered as synergistic anti
      inflammatory effect. A series of novel alpha,beta-unsaturated carbonyl based
      compounds were synthesized and evaluated for their inhibitory activity on
      secretory phospholipase A2 (sPLA2), cyclooxygenases (COX), soybean lipoxygenase
      (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-alpha. Six
      alpha,beta-unsaturated carbonyl based compounds (2, 3, 4, 12, 13 and 14)
      exhibited strong inhibition of sPLA2 activity, with IC50 values in the range of
      2.19-8.76 MUM. Nine compounds 1-4 and 10-14 displayed inhibition of COX-1 with
      IC50 values ranging from 0.37 to 1.77 MUM (lower than that of reference
      compound), whereas compounds 2, 10, 13 and 14 strongly inhibited the COX-2. The
      compounds 10-14 exhibited strong inhibitory activity against LOX enzyme. All
      compounds were evaluated for the inhibitory activities against LPS-induced TNF
      alpha and IL-6 release in the macrophages. On the basis of screening results,
      five active compounds 3, 4, 12, 13 and 14 were found strong inhibitors of TNF
      alpha and IL-6 release in a dose-dependent manner. Molecular docking experiments
      were performed to clarify the molecular aspects of the observed COX and LOX
      inhibitory activities of the investigated compounds. Present findings increases
      the possibility that these alpha,beta-unsaturated carbonyl based compounds might
      serve as beneficial starting point for the design and development of improved
      anti-inflammatory agents.

PMID- 24938496
TI  - Design and synthesis of 5-[(2-chloro-6-fluorophenyl)acetylamino]-3-(4
      fluorophenyl)-4-(4-pyrimidinyl)isoxazole (AKP-001), a novel inhibitor of p38 MAP
      kinase with reduced side effects based on the antedrug concept.
AB  - Inhibitors of p38 mitogen-activated protein (MAP) kinase, which are closely
      involved in the production of inflammatory cytokines, are considered promising
      curative drugs for chronic inflammatory disorders. However, there is also a
      growing concern regarding its systemic side effects. To reduce the occurrence of
      side effects, we have identified a novel p38 MAP kinase inhibitor that shows
      properties of an antedrug, which imparts its effect solely on the inflammatory
      site and is metabolically inactivated right after. We have designed isoxazole
      derivatives through the addition of a fresh interacting fourth site to the
      structure of the prototypical p38 MAP kinase inhibitor that harbors three point
      interactive sites. The derivative 26d (AKP-001) shows excellent p38 MAP kinase
      inhibitory activity and a high selectivity for various kinases. Its rapid
      metabolism has been confirmed in rats. Moreover, 26d has been shown to be
      effective in animal models of inflammatory bowel disease. 

PMID- 24938497
TI  - Regio- and stereoselective hydroxylation of 10-undecenoic acid with a light
      driven P450 BM3 biocatalyst yielding a valuable synthon for natural product
      synthesis.
AB  - We report herein the selective hydroxylation of 10-undecenoic acid with a light
      activated hybrid P450 BM3 enzyme. Under previously developed photocatalytic
      reaction conditions, only a monohydroxylated product is detected by gas
      chromatography. Hydroxylation occurs exclusively at the allylic position as
      confirmed from a synthesized authentic standard. Investigation into the
      stereochemistry of the reaction indicates that the R enantiomer is obtained in
      85% ee. The (R)-9-hydroxy-10-undecenoic acid obtained enzymatically is a valuable
      synthon en route to various natural products further expanding the light
      activated P450 BM3 biocatalysis and highlighting the advantages over traditional
      methods. 

PMID- 24938498
TI  - Serum level and immunohistochemical expression of vascular endothelial growth
      factor for the prediction of postoperative recurrence in renal cell carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) plays a major role in
      angiogenesis. One of the functions of VEGF is to regulate neovascularization in
      clear cell renal cell carcinoma (CCRCC). The objective of our study was to
      examine whether before nephrectomy serum levels of VEGF or expression of VEGF
      using immunohistochemistry (IHC) could predict postoperative recurrence in
      nonmetastatic CCRCC. RESULTS: Twelve patients (14.5%) had recurrence during a
      mean follow-up of 52.6 +/- 31.2 months. The serum VEGF level was significantly
      higher in patients with recurrence than in those without recurrence (P = 0.038).
      High serum VEGF levels were above 416 pg/mL; this value was chosen based on a
      receiver operating characteristic analysis. The recurrence-free survival rate in
      patients with a high serum VEGF level was significantly lower than in those with
      a low serum VEGF level (P = 0.003). In total, tumors from 26 patients (31.3%)
      showed overexpression of VEGF using IHC. The recurrence-free survival rate in the
      IHC-positive group was significantly lower than that in the IHC-negative group (P
      = 0.044). Multivariate analysis indicated that preoperative serum VEGF levels (P
      = 0.013) and female gender (P = 0.004) were independent predictors of
      postoperative recurrence in nonmetastatic CCRCC. CONCLUSIONS: Preoperative serum
      VEGF levels is a useful predictor compared with IHC analysis of VEGF of
      postoperative recurrence in nonmetastatic CCRCC.

PMID- 24938499
TI  - CHF5074 protects SH-SY5Y human neuronal-like cells from amyloidbeta 25-35 and
      tumor necrosis factor related apoptosis inducing ligand toxicity in vitro.
AB  - Alzheimer's disease (AD) is contributed by multiple pathogenic causes. The
      anomalous protein amyloid-beta (Abeta) is regarded as a pivotal factor in AD, and
      originates from enzymatic cleavage of a precursor protein by the secretase
      family. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic
      acid (CHF5074) is a non-steroidal antiinflammatory derivative able to inhibit
      Abeta deposition in the brain of transgenic mouse models of AD. The proapoptotic
      cytokine TRAIL has been reported to mediate Abeta-dependent neurotoxicity. Here,
      the effects of CHF5074 on Abeta25-35- triggered TRAIL toxicity were evaluated in
      the differentiated human neuroblastoma cell line SH-SY5Y in vitro. Cells were pre
      treated 1h with CHF5074 at graded concentrations (range: 1 nM-1 uM) and then
      challenged for 72 h with either Abeta25-35 or TRAIL. Results show that CHF5074
      treatment prevented apoptotic death in SH-SY5Y cell line in a concentration-
      dependent fashion. Its maximally active concentration was 10 nM. Then,
      investigation of related molecular mechanisms underlying such protective effect
      of CHF5074 suggested that the levels of caspases, as well as of various kinases,
      including stress and MAP kinases, are modulated by CHF5074. Finally, treatment of
      injured human neuroblastoma cell line SH-SY5Y with CHF5074 resulted in prominent
      protection from apoptotic death. The bulk of these data suggest that CHF5074
      represents a potential candidate for pharmacological neuroprotective treatment in
      neurodegenerative disorders.

PMID- 24938501
TI  - Depression and anxiety levels increase chronic musculoskeletal pain in patients
      with Alzheimer's disease.
AB  - BACKGROUND/OBJECTIVES: During the next decades a rapid increase is expected in
      the number of patients with dementia suffering from pain who often take less
      medication compared to normal elderly, due to several diagnostic barriers.
      Comorbid mood disorders result in great difficulties in pain assessment and
      further treatment. DESIGN: Twenty five patients with Alzheimer's disease,
      comorbid mood disorders, and chronic musculoskeletal pain (experimental group)
      and thirty one patients with Alzheimer's disease and chronic musculoskeletal pain
      without comorbid mood disorders (control group) were examined. The assessment
      tools used were Geriatric Pain Measure, Patient Health Questionnaire, Pain
      Assessment in Advanced Dementia, Mini Mental State Examination and Pain Anxiety
      Symptom Scale. Statistical analysis was performed by SPSS v17.0, using the
      Pearson correlation and the multiple linear regression analysis. RESULTS: The
      correlation between mood disorders and levels of pain intensity in the
      experimental group was found to be statistically higher than that in the control
      group (p<.001). Among all quantitative variables, highly significant correlation
      (p<.001) was observed between stress and depression symptomatology (r =.550,
      p<.001) in the experimental group. Normal regression analysis was used to assess
      possible differences between demographic data and PASS scores. Scores in fearful
      thinking and physiological responses scales of PASS were higher in female than
      male (p=.014), whereas scores in the cognitive anxiety scale of PASS have shown a
      highly significant positive correlation with years of education (p<.001).
      DISCUSSION: It seems that depression and anxiety are associated with chronic
      musculoskeletal pain intensity in dementia, thus need to be taken into
      consideration by health professionals for patient's management.

PMID- 24938502
TI  - Rivastigmine transdermal patch and physical exercises for Alzheimer's disease: a
      randomized clinical trial.
AB  - OBJECTIVE: To determine the effects of rivastigmine patch associated with
      physical exercise versus rivastigmine patch alone in quality of life (QOL),
      cognition, activities of daily living (ADL) and functional mobility in
      Alzheimer's disease (AD)subjects. METHODS: A randomized, controlled, single
      blinded trial was conducted in 40 patients with mild to moderate stages of AD.
      All patients were daily treated with rivastigmine transdermal patch at a stable
      dose of 4.6 mg and randomized into two groups: physical exercises or control. The
      exercise program consisted of aerobic, flexibility, strength and balance
      movements, twice a week for 6 months. Main outcomes were Quality of Life in
      Alzheimer's disease scale (QOL), Activities of Daily Living Questionnaire (ADL),
      Mini-Mental State Examination (MMSE) and "Time Up and Go Test". RESULTS: Thirty
      four patients completed the study. After 6 months, there was a significant
      improvement in QOL of patients randomized to physical exercise group (P< 0.05).
      In both groups, there was an improvement on caregivers QOL (P>0.05). When
      considering cognitive functions, there was no difference between groups. The
      ability to perform ADL worsened in the group enrolled to RTP alone. There was an
      improvement in functional mobility in the group treated with RTP. CONCLUSION: Our
      results suggest that the association between physical exercises and RTP improves
      QOL in patients with AD. Cognition remained unchanged in both groups. Regarding
      the effect of physical exercises in ADL, further trials are necessary to confirm
      these results.

PMID- 24938503
TI  - Association of SORL1 gene variants with hippocampal and cerebral atrophy and
      Alzheimer's disease.
AB  - BACKGROUND: Sortilin-related receptor, Sorl1, is a neuronal receptor that
      interacts with the amyloid precursor protein to regulate amyloidogenesis.
      Variants in the gene encoding Sorl1 are associated with Alzheimer's disease (AD),
      as well as its neuroimaging markers. OBJECTIVES: To investigate the relationship
      between SORL1 gene variants with ADrelated brain morphologies and AD, testing for
      sex-specific effects. METHODS: The sample comprised 292 individuals aged >= 75
      years participating in the longitudinal Sydney Older Persons Study. A sub-sample
      also underwent a brain MRI scan (n=102, 53 males; 49 females). The relationships
      of three SORL1 single nucleotide polymorphisms (SNPs): rs4935774, rs2298813,
      rs1133174 with brain MRI measures, and AD were determined. RESULTS: Significant
      associations of SORL1 variants with cross-sectional brain MRI measures and AD
      were observed only when the sample was stratified by sex. The most common
      haplotype (H1), comprising rs4935774-T, rs2298813-G, and rs1133174-G alleles
      (T/G/G) was associated with whole brain atrophy in both males and females
      (p=0.012 & p=0.013; respectively). Only SNP rs1133174 was individually associated
      with hippocampal atrophy in males (p= 0.039) and females (p=0.025). Of the 292
      participants, 111 had either probable or possible AD. A significant association
      of H1 with AD (p = 0.017) was observed in females. A nominally significant
      association of SNP rs1133174 with AD (p = 0.051) was also observed in the whole
      cohort. CONCLUSION: The results provide evidence that the association of
      polymophisms in the sortilin-related receptor gene (SORL1) with AD and its MRI
      biomarkers of brain and hippocampal atrophy are moderated by sex.

PMID- 24938500
TI  - Biomarkers of Alzheimer's disease risk in peripheral tissues; focus on buccal
      cells.
AB  - Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and
      is the most common form of dementia. To-date no simple, inexpensive and minimally
      invasive procedure is available to confirm with certainty the early diagnosis of
      AD prior to the manifestations of symptoms characteristic of the disease.
      Therefore, if population screening of individuals is to be performed, more
      suitable, easily accessible tissues would need to be used for a diagnostic test
      that would identify those who exhibit cellular pathology indicative of mild
      cognitive impairment (MCI) and AD risk so that they can be prioritized for
      primary prevention. This need for minimally invasive tests could be achieved by
      targeting surrogate tissues, since it is now well recognized that AD is not only
      a disorder restricted to pathology and biomarkers within the brain. Human buccal
      cells for instance are accessible in a minimally invasive manner, and exhibit
      cytological and nuclear morphologies that may be indicative of accelerated ageing
      or neurodegenerative disorders such as AD. However, to our knowledge there is no
      review available in the literature covering the biology of buccal cells and their
      applications in AD biomarker research. Therefore, the aim of this review is to
      summarize some of the main findings of biomarkers reported for AD in peripheral
      tissues, with a further focus on the rationale for the use of the buccal mucosa
      (BM) for biomarkers of AD and the evidence to date of changes exhibited in buccal
      cells with AD. 

PMID- 24938505
TI  - Shaping thin nematic films with competing boundary conditions.
AB  - Free interfaces of liquid crystals tend to minimise both capillarity and
      anchoring forces. Here we study nematic films in planar and radial geometries
      with antagonistic anchoring boundary conditions and one deformable interface.
      Assuming a perturbation ansatz we study possible couplings of the director
      configuration with the shape of free interfaces. In the long-wavelength limit
      independent of the surface tension, we find analytically the threshold thickness
      when the flat film becomes unstable. Next we quantify the bifurcation of a
      circular ring towards structures with m-fold rotational symmetry, induced by
      elastic anisotropy of the nematic director in the bulk. We believe that our
      simplified approach can give additional insight into elastic and capillary
      phenomena of materials with inherent liquid crystalline order and free
      interfaces. 

PMID- 24938504
TI  - Does an interdisciplinary network improve dementia care? Results from the IDemUck
      study.
AB  - BACKGROUND: Most persons with dementia live at home and are treated in the
      primary care. However, the ambulatory health care system in Germany contains a
      lot of "interface problems" and is not optimized for the future challenges.
      Innovative concepts like regional networks in dementia care exist on a project
      level and need to be tested for efficacy to encourage implementation. The goal of
      the study is the scientific evaluation of an already existing regional dementia
      network. METHODS: Prospective randomized controlled trial of 235 community-living
      elderly with dementia and their family caregivers of network treatment (n=117)
      compared to usual care (n=118) in a predominantly rural region. The allocation to
      intervention or control group was based on network membership of their General
      Practitioner. Intervention patients received diagnostic evaluation and subsequent
      treatment according to network guidelines. Main outcome measures were the early
      contact with a neurologic or psychiatric specialist and dementia-specific
      medication as well as quality of life of the patients, and as secondary outcomes
      caregiver burden and caregiver health-related quality of life. RESULTS: Network
      patients were more likely to receive antidementive drugs (50.5 % vs. 35.8 %;
      p=0.035) and had more often contact to a neurologist (18.6 % vs. 2.8 %; p<0.001).
      No group differences were found on patient's quality of life nor overall effects
      or treatment by time effects. Intervention caregivers reported no significant
      improvements in health related quality of life measured by SF-36 and EQ-5D.
      CONCLUSION: The management of dementia patients in an interdisciplinary regional
      network solelyprovides measurable advantages with respect to the provision of
      dementia-specific medication and utilization of medical treatment i.e. referral
      rates to specialists. Further evaluation research is needed to identify relevant
      mechanismsof collaborative processes with respect to their impact on patient and
      caregiver related outcomes.

PMID- 24938506
TI  - Hemoglobin and hip fracture risk in older non-Hispanic white adults.
AB  - SUMMARY: The relationship between hemoglobin and hip fracture was examined in
      older non-Hispanic white adults from the third National Health and Nutrition
      Examination Survey (NHANES III). Both low and high hemoglobin values were
      associated with increased hip fracture risk before and after adjusting for
      selected risk factors. INTRODUCTION: The few studies to date that have examined
      the relationship between hemoglobin and fracture risk have focused on low
      hemoglobin values. The present study examined hip fracture risk across the
      hemoglobin distribution in older non-Hispanic white adults from the third
      National Health and Nutrition Examination Survey (NHANES III, 1988-1994).
      METHODS: Hemoglobin was measured using a Coulter S-plus Jr.(r) (Coulter
      Electronics, Hialeah, FL) in 2,122 non-Hispanic whites age 65 years and older.
      Hip fracture cases were identified using linked Medicare and mortality records
      obtained through 2007. Cox proportional hazards models were used to assess the
      best-fitting model and to estimate the hazards ratio (HR) for hip fracture by
      hemoglobin decile before and after adjusting for selected confounders. RESULTS:
      There were 239 hip fracture cases in the analytic sample. The best fitting model
      was quadratic. When compared to values in the middle of the distribution, those
      with hemoglobin in the lowest and highest deciles had increased hip fracture risk
      (HRlowest decile = 2.96, 95 % confidence interval (CI) 1.44-6.08; HRhighest
      decile = 2.06, 95 % CI 1.09-3.92) after adjusting for age and sex. Both HRs
      remained significant after adjusting for additional confounders (HRlowest decile
      = 2.24, 95 % CI 1.09-3.92; HRhighest decile = 2.37, 95 % CI 1.35-4.16).
      CONCLUSIONS: Both low and high hemoglobin values were associated with increased
      hip fracture risk. The mechanism underlying the relationship is not clear, but
      there were some suggestions that it may differ for low versus high hemoglobin.

PMID- 24938507
TI  - EM for phylogenetic topology reconstruction on nonhomogeneous data.
AB  - BACKGROUND: The reconstruction of the phylogenetic tree topology of four taxa is,
      still nowadays, one of the main challenges in phylogenetics. Its difficulties lie
      in considering not too restrictive evolutionary models, and correctly dealing
      with the long-branch attraction problem. The correct reconstruction of 4-taxon
      trees is crucial for making quartet-based methods work and being able to recover
      large phylogenies. METHODS: We adapt the well known expectation-maximization
      algorithm to evolutionary Markov models on phylogenetic 4-taxon trees. We then
      use this algorithm to estimate the substitution parameters, compute the
      corresponding likelihood, and to infer the most likely quartet. RESULTS: In this
      paper we consider an expectation-maximization method for maximizing the
      likelihood of (time nonhomogeneous) evolutionary Markov models on trees. We study
      its success on reconstructing 4-taxon topologies and its performance as input
      method in quartet-based phylogenetic reconstruction methods such as QFIT and
      QuartetSuite. Our results show that the method proposed here outperforms neighbor
      joining and the usual (time-homogeneous continuous-time) maximum likelihood
      methods on 4-leaved trees with among-lineage instantaneous rate heterogeneity,
      and perform similarly to usual continuous-time maximum-likelihood when data
      satisfies the assumptions of both methods. CONCLUSIONS: The method presented in
      this paper is well suited for reconstructing the topology of any number of taxa
      via quartet-based methods and is highly accurate, specially regarding largely
      divergent trees and time nonhomogeneous data.

PMID- 24938510
TI  - Dermal exposure from transfer of lubricants and fuels by consumers.
AB  - Consumer uses of fuels and lubricants in Europe are subject to the Registration,
      Evaluation, Authorization and restriction of CHemicals (REACH) legislation. Ten
      volunteers completed a series of exposure situations to simulate filling a
      vehicle fuel tank with diesel (ES1 Diesel), adding lubricant to a car engine (two
      situations, one filling point easier to reach (ES2 Easy) than the other (ES3
      Hard)) and lubricating a bicycle chain (ES4 Bike). Dermal exposure to the hands
      and forearms was assessed using a wipe sampling method. A high proportion of
      samples was less than the limit of detection (ES1=38%, ES3=60%, ES2 and 4, both
      78%). In ES1 Diesel, dermal exposure to the hands and forearms ranged from <0.25
      MUg/cm(2) to 96.21 MUg/cm(2). Significantly higher dermal exposure was observed
      when a lower level of care was taken to complete the task. In ES2 Easy and ES3
      Hard, the hand and forearm results ranged from <0.1 MUg/cm(2) to 3.33 MUg/cm(2)
      and from <0.1 MUg/cm(2) to 3.54 MUg/cm(2), respectively. In ES4 Bike, the hand
      and forearm exposures ranged from <0.35 MUg/cm(2) to 5.25 MUg/cm(2). Not all
      volunteers fully complied with the ES4 instructions, thus highlighting that this
      situation may have more variability in consumer behaviour. The ratio of the
      amount measured on the hands and forearms to the amount of product handled for
      ES1 Diesel, ES2 Easy and ES3 Hard was less than 0.0001%, for ES4 Bike it was
      0.04%. Mixed effect models showed that the between and within volunteer
      variations are small for all except ES1 Diesel, where the within volunteer
      variation was relatively large (likely due to the few high measurements). This
      study reports dermal exposure measurement data, which will be of value when
      updating REACH and other exposure assessments for these, and similar, petroleum
      products. 

PMID- 24938509
TI  - Renal tubular dysfunction increases mortality in the Japanese general population
      living in cadmium non-polluted areas.
AB  - The aim of this study was to establish the cause-effect relationship between
      renal tubular dysfunction and mortality. A 19-year cohort study was conducted in
      900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted
      areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary
      beta2-microglobulin (beta2-MG) and N-acetyl-beta-glucosaminidase (NAG) for
      mortality were calculated using a proportional hazard regression. Forward
      stepwise model selection was applied to the potential covariates such as age,
      body mass index, mean arterial pressure, various lifestyle factors and present
      illness. Simultaneously, the dose-effect relationship between renal tubular
      markers and urinary cadmium at baseline was evaluated using multiple regression
      analyses. In men, HR was significant for beta2-MG (HR corresponding to an
      increase of 100 MUg/g cre: 1.02) and NAG (HR corresponding to an increase of 1
      IU/g cre: 1.05). In women, a significant HR was observed for beta2-MG (HR
      corresponding to an increase of 100 MUg/g cre: 1.01) and NAG (HR corresponding to
      an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for
      urinary cadmium and all renal tubular markers in men and women. The present study
      indicated that renal tubular dysfunction was significantly related to mortality
      in the general population of cadmium non-polluted areas in Japan.

PMID- 24938508
TI  - Ambient polycyclic aromatic hydrocarbons and pulmonary function in children.
AB  - Few studies have examined the relationship between ambient polycyclic aromatic
      hydrocarbons (PAHs) and pulmonary function in children. Major sources include
      vehicular emissions, home heating, wildland fires, agricultural burning, and
      power plants. PAHs are an important component of fine particulate matter that has
      been linked to respiratory health. This cross-sectional study examines the
      relationship between estimated individual exposures to the sum of PAHs with 4, 5,
      or 6 rings (PAH456) and pulmonary function tests (forced expiratory volume in one
      second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity)
      in asthmatic and non-asthmatic children. We applied land-use regression to
      estimate individual exposures to ambient PAHs for averaging periods ranging from
      1 week to 1 year. We used linear regression to estimate the relationship between
      exposure to PAH456 with pre- and postbronchodilator pulmonary function tests in
      children in Fresno, California (N=297). Among non-asthmatics, there was a
      statistically significant association between PAH456 during the previous 3
      months, 6 months, and 1 year and postbronchodilator FEV1. The magnitude of the
      association increased with the length of the averaging period ranging from 60 to
      110 ml decrease in FEV1 for each 1 ng/m(3) increase in PAH456. There were no
      associations with PAH456 observed among asthmatic children. We identified an
      association between annual PAHs and chronic pulmonary function in children
      without asthma. Additional studies are needed to further explore the association
      between exposure to PAHs and pulmonary function, especially with regard to
      differential effects between asthmatic and non-asthmatic children. 

PMID- 24938512
TI  - [Qualitative analysis of the integration of sex education for young people in
      audio-visual media in Kinshasa Democratic Republic of Congo].

PMID- 24938511
TI  - Physiological and perceived health effects from daily changes in air pollution
      and weather among persons with heart failure: a panel study.
AB  - We carried out this daily diary panel study in Montreal, Quebec, to determine
      whether oxygen saturation, pulse rate, blood pressure, self-rated health, and
      shortness of breath at night were associated with concentrations of indoor carbon
      monoxide (CO), and indoor and outdoor fine particles (PM2.5), temperature, and
      relative humidity. Over a 2-month consecutive period between 2008 and 2010, we
      measured daily indoor and outdoor levels of the air pollutants and weather
      variables and 55 subjects measured their daily health and other variables. To
      estimate the associations between the health outcomes and the environmental
      exposures, we used a mixed effects regression model using an autoregressive model
      of order-one and we adjusted for month and day and personal variables. The
      general pattern of associations can be summarized as follows: oxygen saturation
      was reduced for increases in indoor- and outdoor-PM2.5 and temperature. Pulse
      rate increased on the concurrent day for increases in indoor CO and PM2.5.
      Diastolic blood pressure increased with increasing indoor and outdoor PM2.5 and
      relative humidity. Systolic blood pressure increased with indoor PM2.5 and
      decreased with increasing indoor and outdoor temperature. Self-rated health
      diminished with increases in outdoor PM2.5 and indoor and outdoor temperature.
      Self-reported shortness of breath at night increased with increasing indoor and
      outdoor temperatures. Health in heart failure is affected in the short term by
      personal and environmental conditions that are manifest in intermediate
      physiological parameters. 

PMID- 24938513
TI  - A call for an urgent ban on E-cigarettes in India--a race against time.
AB  - Being the second largest consumer of tobacco in the world and with more than 65%
      of its population below the age of 35, India would face electronic cigarettes
      (ECs) as an enormous public health challenge in future. In the absence of
      established facilities for tobacco cessation in the country, ECs may provide an
      additional opportunity for the industry to project itself as a harm-reduction
      crusader. Regulating ECs as tobacco products or as drugs is not a prudent option
      in the Indian context. Banning ECs seems to be the most plausible approach at
      present. However, in the long run, India should be open to new research. More
      significantly, policy makers in India should be wary of the lead time before a
      ban is implemented-a shorter intervening period could ensure that a well
      established, better politically connected and more defiant EC industry,
      aggressively promoting ECs to Indian youth, never becomes a reality. 

PMID- 24938514
TI  - Establishing a disability-inclusive agenda for sustainable development in 2015
      and beyond.
AB  - Disability was omitted from the Millennium Declaration and eight Millennium
      Development Goals. As a result, individuals with disabilities and their
      advocates, health-related agencies and major United Nations (UN) groups
      collaborated to explicate the rights and needs of persons with disabilities. A
      community empowerment approach was guided by the Convention on the Rights of
      Persons with Disabilities, input from expert groups, public meetings held across
      the globe, questionnaires sent to civil society representatives, and rich online
      conversation. Persons with disabilities have the right to health, education,
      gainful employment, social protection, and participation in political and public
      life. Selected results from The World We Want consultation for the topic of
      'Inequalities and a disability-inclusive agenda' illustrate the potential of
      reaching consensus among a broad array of constituents, informing decisions about
      policy and practice. 

PMID- 24938515
TI  - Strong adverse prognostic impact of hyperglycemic episodes during adjuvant
      chemoradiotherapy of glioblastoma multiforme.
AB  - BACKGROUND: In comparison to normal brain tissue, glioblastomas exhibit
      significantly increased glucose uptake. Brain edema is a common complication
      during adjuvant chemoradiotherapy, leading to a requirement for glucocorticoid
      treatment. Glucocorticoid treatment frequently causes considerable deregulation
      of blood glucose levels. Therefore, episodes of hyperglycemia may contribute to
      radio- and/or chemoresistance. PATIENTS AND METHODS: This study comprises a
      retrospective analysis of the influence of hyperglycemic episodes (HEs) during
      adjuvant therapy on the overall survival of 106 glioblastoma multiforme patients.
      RESULTS: The occurrence of one or more deregulated blood glucose value(s) > 10 mM
      is associated with a reduction in median overall survival from 16.7 to 8.8
      months. A significantly poorer overall survival of patients with hyperglycemia
      could also be detected in subgroup analyses of patients with complete tumor
      resection and complete treatment according to the EORTC 22891/26891 trial
      protocol, as well as in a multivariate Cox proportional hazards analysis. A
      history of diabetes mellitus had no influence on prognosis. DISCUSSION: Our data
      suggest that the observed negative impact of elevated blood glucose levels on
      overall survival may not solely be explained by the patients' poorer general
      condition; the elevated blood glucose concentration itself may play a
      pathogenetic role. This could be due to increased activity of antioxidant
      systems, elevated expression of DNA damage response proteins and protection of
      hypoxic tumor cells against apoptosis combined with hypoxia-mediated
      radioresistance. CONCLUSION: A possible prognostic impact of elevated blood
      glucose levels during the period of adjuvant (chemo-) radiotherapy of
      glioblastoma should be evaluated in a prospective clinical trial.

PMID- 24938516
TI  - The Computer-Vision Symptom Scale (CVSS17): development and initial validation.
AB  - PURPOSE: To develop a questionnaire (in Spanish) to measure computer-related
      visual and ocular symptoms (CRVOS). METHODS: A pilot questionnaire was created by
      consulting the literature, clinicians, and video display terminal (VDT) workers.
      The replies of 636 subjects completing the questionnaire were assessed using the
      Rasch model and conventional statistics to generate a new scale, designated the
      Computer-Vision Symptom Scale (CVSS17). Validity and reliability were determined
      by Rasch fit statistics, principal components analysis (PCA), person separation,
      differential item functioning (DIF), and item-person targeting. To assess
      construct validity, the CVSS17 was correlated with a Rasch-based visual
      discomfort scale (VDS) in 163 VDT workers, this group completed the CVSS17 twice
      in order to assess test-retest reliability (two-way single-measure intraclass
      correlation coefficient [ICC] and their 95% confidence intervals, and the
      coefficient of repeatability [COR]). RESULTS: The CVSS17 contains 17 items
      exploring 15 different symptoms. These items showed good reliability and internal
      consistency (mean square infit and outfit 0.88-1.17, eigenvalue for the first
      residual PCA component 1.37, person separation 2.85, and no DIF). Pearson's
      correlation with VDS scores was 0.60 (P < 0.001). Intraclass correlation
      coefficient for test-retest reliability was 0.849 (95% confidence interval [CI],
      0.800-0.887), and COR was 8.14. CONCLUSIONS: The Rasch-based linear-scale CVSS17
      emerged as a useful tool to quantify CRVOS in computer workers. : Spanish
      Abstract.

PMID- 24938517
TI  - Biomechanical characterization of keratoconus corneas ex vivo with Brillouin
      microscopy.
AB  - PURPOSE: Loss of corneal strength is a central feature of keratoconus
      progression. However, it is currently difficult to measure corneal mechanical
      changes noninvasively. The objective of this study is to evaluate if Brillouin
      optical microscopy can differentiate the mechanical properties of keratoconic
      corneas versus healthy corneas ex vivo. METHODS: We obtained eight tissue samples
      from healthy donor corneas used in Descemet's stripping endothelial keratoplasty
      (DSEK) and 10 advanced keratoconic corneas from patients undergoing deep anterior
      lamellar keratoplasty (DALK). Within 2 hours after surgery, a confocal Brillouin
      microscope using a monochromatic laser at 532 nm was used to map the Brillouin
      frequency shifts of the corneas. RESULTS: The mean Brillouin shift in the
      anterior 200 MUm of the keratoconic corneas at the cone was measured to be 7.99
      +/- 0.10 GHz, significantly lower than 8.17 +/- 0.06 GHz of the healthy corneas
      (P < 0.001). The Brillouin shift in the keratoconic corneas decreased with depth
      from the anterior toward posterior regions with a steeper slope than in the
      healthy corneas (P < 0.001). Within keratoconic corneas, the Brillouin shift in
      regions away from the apex of the cone was significantly higher than within the
      cone region (P < 0.001). CONCLUSIONS: Brillouin measurements revealed notable
      differences between healthy and keratoconic corneas. Importantly, Brillouin
      imaging showed that the mechanical loss is primarily concentrated within the area
      of the keratoconic cone. Outside the cone, the Brillouin shift was comparable
      with that of healthy corneas. The results demonstrate the potential of Brillouin
      microscopy for diagnosis and treatment monitoring of keratoconus.

PMID- 24938518
TI  - High glucose alters Cx43 expression and gap junction intercellular communication
      in retinal Muller cells: promotes Muller cell and pericyte apoptosis.
AB  - PURPOSE: To investigate whether high glucose (HG) alters connexin 43 (Cx43)
      expression and gap junction intercellular communication (GJIC) activity in
      retinal Muller cells, and promotes Muller cell and pericyte loss. METHODS:
      Retinal Muller cells (rMC-1) and cocultures of rMC-1 and retinal pericytes were
      grown in normal (N) or HG (30 mM glucose) medium. Additionally, rMC-1 transfected
      with Cx43 small interfering RNA (siRNA) were grown as cocultures with pericytes,
      and rMC-1 transfected with Cx43 plasmid were grown in HG. Expression of Cx43 was
      determined by Western blotting and immunostaining and GJIC was assessed by scrape
      loading dye transfer (SLDT) technique. Apoptosis was analyzed by TUNEL or
      differential staining assay, and Akt activation by assessing Akt phosphorylation.
      RESULTS: In monocultures of rMC-1 and cocultures of rMC-1 and pericytes, Cx43
      protein level, number of Cx43 plaques, GJIC, and Akt phosphorylation were
      significantly reduced in HG medium. Number of TUNEL-positive cells was also
      significantly increased in rMC-1 monocultures and in rMC-1 and pericyte
      cocultures grown in HG medium. Importantly, when rMC-1 transfected with Cx43
      siRNA were grown as cocultures with pericytes, a significant decrease in GJIC,
      and increase in TUNEL-positive cells was observed, concomitant with decreased Akt
      phosphorylation. Upregulation of Cx43 rescued rMC-1 from HG-induced apoptosis.
      CONCLUSIONS: Gap junction communication between Muller cells and pericytes is
      essential for their survival. Downregulation of Cx43 that is HG induced and
      impairment of GJIC activity in Muller cells contributes to loss of glial and
      vascular cells associated with the pathogenesis of diabetic retinopathy.

PMID- 24938519
TI  - Morphological alterations within the peripheral fixation of the iris dilator
      muscle in eyes with pigmentary glaucoma.
AB  - PURPOSE: To analyze the peripheral fixation of the iris dilator muscle in normal
      eyes and in eyes with pigmentary glaucoma (PG). METHODS: Using 63 control eyes
      (age 18 months-99 years), the peripheral iris dilator was investigated by light
      microscopy, immunohistochemistry, and electron microscopy. Development was
      studied using 18 differently aged fetal eyes stained immunohistochemically
      against alpha-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG
      was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed
      eyes from three donors aged 38, 62, and 74 years. RESULTS: In normal eyes, the
      peripheral end of the iris dilator muscle is arranged in a sphincter-like manner.
      Arcade-shaped tendinous connections associated with myofibroblasts (iridial
      strands) anchor the iris dilator within the elastic-fibromuscular ciliary
      meshwork that also serves as fixation area for the elastic tendons of the inner
      ciliary muscle portions. The iridial strands are innervated and can adapt their
      length during accommodation. The PG eyes show incomplete circular bundles and
      iridial strands that are mainly anchored to the iris stroma and the flexible
      uveal parts of the trabecular meshwork. CONCLUSIONS: The normal anchorage of the
      peripheral iris dilator and its presumably neuronally regulated length adaptation
      stabilize the peripheral iris during accommodation. Insufficient fixation in PG
      could promote posterior bowing of the iris with rubbing against the zonular
      fibers and pigment liberation from the iris pigmented epithelium.

PMID- 24938520
TI  - Comparison of procedures for the extraction of supernatants and cytotoxicity
      tests in Vero cells, applied to assess the toxigenic potential of Bacillus spp.
      and Lactobacillus spp., intended for use as probiotic strains.
AB  - Interest in using Bacillus strains as probiotic components of animal feeds has
      grown in recent years. However, some of these strains, especially those
      taxonomically related to the Bacillus cereus group, may have enterotoxigenic
      activity. Assessment of their toxigenic potential by well-established and robust
      protocols is required before authorizing their use in animal nutrition. Three
      methods of extraction and concentration of supernatants of Bacillus and
      Lactobacillus strains (methanol extraction, ammonium sulphate and ultrafiltration
      concentration) and three cytotoxic tests in Vero cells (WST-1, LDH and protein
      synthesis inhibition assays) for the assessment of the cytotoxicity activity of
      Lactobacillus strains (as probiotic strains in human and animal nutrition) and
      Bacillus toyonensis BCT-7112(T) (as animal probiotic strain in animal nutrition
      Toyocerin(r)-) were evaluated in this study. Methanol extraction was not useful
      under any circumstances. The other two concentration methods (ammonium sulphate
      and ultrafiltration) were feasible, with slightly greater sensitivity achieved by
      ultrafiltration. The probiotic strain B. toyonensis BCT-7112(T) proved to be a
      non-cytotoxic strain in all the protocols tested. However, some Lactobacillus
      strains showed cytotoxicity activity, regardless of the protocols applied. 

PMID- 24938521
TI  - Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts.
AB  - PURPOSE: Management guidelines for pancreatic intraductal papillary mucinous
      neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption
      that mucinous cysts can be accurately distinguished from other pancreatic cystic
      lesions. Previous studies using surgical material have identified recurrent
      mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic
      utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic
      ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. EXPERIMENTAL DESIGN:
      GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91
      pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic
      pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3
      retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. RESULTS: Mutations
      in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma.
      KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with
      adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%)
      IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found
      in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial
      cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI),
      0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation.
      Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and
      84% sensitivity (95% CI, 0.70-0.92). CONCLUSIONS: The combination of GNAS and
      KRAS testing was highly specific and sensitive for IPMNs; however, the lack of
      sensitivity for MCNs highlights the need for additional markers to improve the
      detection of pancreatic mucinous neoplasms.

PMID- 24938523
TI  - Targeting cancer cells via the reactive oxygen species-mediated unfolded protein
      response with a novel synthetic polyphenol conjugate.
AB  - PURPOSE: The selective killing of tumor cells is an important strategy for cancer
      therapeutics. The aim of this study was to develop a novel antitumor agent that
      is safe for normal cells with the ability to selectively target cancer cells.
      EXPERIMENTAL DESIGN: On the basis of quantitative structure-activity
      relationship, we synthesized a novel polyphenol conjugate (E)-3-(3,5
      dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP-23). We evaluated the
      effect of DPP-23 on proliferation, cell cycle, and apoptosis in various tumor
      cells. We also assessed molecular targets of DPP-23 using genome-wide expression
      profiling by DNA microarray and real-time PCR array systems. RESULTS: DPP-23
      effectively inhibited the growth of cancer cells in vitro and in vivo (xenografts
      in Balb/c nude mice). At a molecular level, DPP-23 targeted the unfolded protein
      response (UPR) in the endoplasmic reticulum (ER) through the production of
      reactive oxygen species (ROS) in cancer cells, but not in normal cells, resulting
      in selective killing of tumor cells via caspase-dependent apoptosis. CONCLUSIONS:
      The selective generation of ROS in cancer cells could be an attractive strategy
      for the selective killing of cancer cells, while maintaining negligible
      cytotoxicity to normal cells. DPP-23 represents a promising novel therapeutic
      agent for the selective production of ROS in cancer cells.

PMID- 24938522
TI  - Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with
      pancreatic cancer: implications for early disease detection.
AB  - PURPOSE: Biomarkers for the early detection of pancreatic cancer are urgently
      needed. The primary objective of this study was to evaluate whether increased
      levels of serum CA19-9, CA125, CEACAM1, and REG3A are present before clinical
      presentation of pancreatic cancer and to assess the performance of combined
      markers for early detection and prognosis. EXPERIMENTAL DESIGN: This nested case
      control study within the UKCTOCS included 118 single and 143 serial serum samples
      from 154 postmenopausal women who were subsequently diagnosed with pancreatic
      cancer and 304 matched noncancer controls. Samples were split randomly into
      independent training and test sets. CA19-9, CA125, CEACAM1, and REG3A were
      measured using ELISA and/or CLIA. Performance of markers to detect cancers at
      different times before diagnosis and for prognosis was evaluated. RESULTS: At 95%
      specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up
      to 2 years before diagnosis. Combining CA19-9 and CA125 improved sensitivity as
      CA125 was elevated (>30 U/mL) in approximately 20% of CA19-9-negative cases.
      CEACAM1 and REG3A were late markers adding little in combined models. Average
      lead times of 20 to 23 months were estimated for test-positive cases.
      Prediagnostic levels of CA19-9 and CA125 were associated with poor overall
      survival (HR, 2.69 and 3.15, respectively). CONCLUSIONS: CA19-9 and CA125 have
      encouraging sensitivity for detecting preclinical pancreatic cancer, and both
      markers can be used as prognostic tools. This work challenges the prevailing view
      that CA19-9 is upregulated late in the course of pancreatic cancer development.

PMID- 24938524
TI  - Circulating CD4+ T cells that produce IL4 or IL17 when stimulated by melan-A but
      not by NY-ESO-1 have negative impacts on survival of patients with stage IV
      melanoma.
AB  - PURPOSE: We initially observed that the presence of circulating NY-ESO-1- and/or
      Melan-A-specific T cells in patients with stage IV melanoma was significantly
      associated with prolonged survival. Here, we report the ways in which the
      phenotypes and functions of these T cells differentially affect survival in
      patients preselected for NY-ESO-1 and/or Melan-A reactivity. EXPERIMENTAL DESIGN:
      We assayed functional antigen-reactive T cells recognizing NY-ESO-1 and/or Melan
      A after in vitro stimulation using overlapping peptide pools. After
      restimulation, we assayed six cytokines simultaneously by intracellular cytokine
      staining. This allowed us to analyze the functional antigen response of both
      CD4(+) and CD8(+) T cells at the single-cell level. RESULTS: We observed that NY
      ESO-1 stimulated mainly CD4(+) T cells, whereas Melan-A more often stimulated
      CD8(+) T cells. NY-ESO-1 reactivity was not associated with an additional impact
      on survival, whether CD4(+) T cells, CD8(+) T cells, or both types of T cells
      were responding. In contrast, recognition of Melan-A by CD4(+) T cells was
      associated with reduced survival in our cohort of patients preselected for NY-ESO
      1 and/or Melan-A reactivity (that is, in patients with exceptionally long
      survival). We further observed a negative effect on survival in patients with
      CD4(+) T cells producing IL4 and IL17 upon Melan-A stimulation. Their prognosis
      was comparable to patients without any Melan-A reactivity. CONCLUSIONS: The
      nature and prognostic impact of specific T-cell responses is different according
      to targeted antigen. Independent from phenotype and functional aspects, NY-ESO-1
      reactivity is associated with good prognosis. In terms of Melan-A, antigen
      specific CD8(+) but not CD4(+) responses are associated with prolonged survival.
      Clin Cancer Res; 20(16); 4390-9. (c)2014 AACR.

PMID- 24938525
TI  - Inflammatory bowel disease.
AB  - Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative
      colitis (UC), are chronic, relapsing inflammatory condition of the
      gastrointestinal tract. CD and UC have distinct pathologic and clinical
      characteristics and despite the extensive amount of research conducted over the
      past decades, their pathogenesis remains still poorly understood. So far, the
      accepted dogma is that IBD results from dysregulated mucosal immune response to
      environmental factors in genetical susceptible hosts. Various components are
      implicated in the pathogenesis of IBD, including genetic susceptibility,
      environmental and microbial factors, intestinal epithelial cells and components
      of innate and adaptive immune system. Given the complexity of IBD, several
      different animal models of IBD have been developed during the last years. Animal
      models are very important tools to study the involvement of various factors in
      the pathogenesis of IBD and, importantly, to test new therapeutic options. This
      review examines some of the key components that have been found to be closely
      associated to IBD and describe the distinct features of some of the most
      important IBD models. 

PMID- 24938527
TI  - Psychosocial predictors of primiparous breastfeeding initiation and duration.
AB  - BACKGROUND: Many US women fall short of meeting the recommendations on
      breastfeeding. Whereas prenatal demographic factors have been well researched in
      relation to breastfeeding, psychosocial maternal characteristics are less
      understood but could be important predictors of breastfeeding initiation and
      duration. OBJECTIVE: This study examined primiparous maternal psychosocial
      characteristics and temperamentally based negative infant affect as predictors of
      breastfeeding initiation and duration while accounting for depression and
      sociodemographic covariates. METHODS: Prenatally, 237 primiparous women were
      administered the Adult Attachment Interview and completed a measure of beliefs
      related to infant crying. At 6 months postpartum, negative infant affect was
      assessed via mother report. Breastfeeding was assessed at 6 months and 1 year
      postpartum via mother report. RESULTS: Results indicated that younger, low
      income, less educated, single, ethnic minority mothers and mothers with elevated
      depressive symptoms were less likely to initiate breastfeeding and breastfed for
      a shorter period than other women. Women who initiated breastfeeding tended to
      have higher adult attachment coherence scores (more secure attachment) than those
      who did not initiate breastfeeding (median score of 6.00 vs 4.00). An interaction
      was observed between negative infant affect and beliefs about crying related to
      spoiling, such that earlier cessation of breastfeeding was observed among mothers
      who reported high levels of negative infant affect and strongly endorsed the
      belief that responding to cries spoils infants (hazard ratio = 1.71, P < .01).
      CONCLUSION: Although these psychosocial variables predicted relatively little
      variation in breastfeeding over and above covariates, the results suggest some
      novel approaches to promote breastfeeding.

PMID- 24938528
TI  - Polyunsaturated fatty acid content may be increased in the milk of women with
      pregnancy-associated breast cancer.
AB  - BACKGROUND: Pregnancy-associated breast cancer (PABC) is aggressive and difficult
      to diagnose. High intake of most types of dietary fat is thought to increase
      breast cancer risk; however, results in humans supporting this premise remain
      equivocal. Fatty acid (FA) concentrations in the body comprise both dietary
      intake and endogenous FA production. Most assessments of FA levels have been
      performed on blood, with little information on the effect of FA levels in breast
      milk on PABC risk. OBJECTIVE: This study aimed to determine if FA concentrations
      in the milk from women diagnosed with breast cancer while nursing were different
      in the cancer-containing breast and opposite breast. METHODS: We quantified 16
      long-chain FA and soluble FA synthase (sFAS) enzyme levels from 4 women diagnosed
      with PABC, comparing results from the cancer-containing breast to those from the
      normal breast. RESULTS: Fatty acid concentrations consistently exceeded and
      trended higher (P < .10) in each cancer-containing breast for 20:4n-6
      (arachidonic acid [AA]), 20:5n-3 (eicosapentaenoic acid [EPA]), and 22:5n-6
      (docosapentaenoic acid [DPA]). Soluble FA synthase levels were similar in the
      cancer-containing and normal breasts. CONCLUSION: Breast milk concentrations of
      AA, EPA, and DPA increased in the cancer-containing breast of women with PABC.
      This increase was not associated with higher sFAS levels.

PMID- 24938526
TI  - Predictors of suboptimal CD4 response among women achieving virologic suppression
      in a randomized antiretroviral treatment trial, Africa.
AB  - BACKGROUND: A subset of HIV-1 infected patients starting highly active
      antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite
      virologic suppression. We studied the rate of and risk factors for SCR among
      women starting HAART in the ACTG A5208 study conducted in 7 African countries.
      741 HAART-naive women with screening CD4 count <200 cells/MUL were randomized to
      start HAART with Tenofovir/Emtricitabine plus either Nevirapine or
      Lopinavir/Ritonavir. METHODS: This analysis includes the 625 women who remained
      on-study through 48 weeks without experiencing protocol-defined virologic
      failure. We defined SCR as<100 CD4 cells/MUL increase from baseline and absolute
      CD4 cell count<350 cells/MUL, both at 48 weeks after HAART initiation. RESULTS:
      The baseline characteristics for the 625 women prior to HAART initiation were:
      median age 33 years, screening CD4 count 134 cells/MUL, and HIV-1 RNA 5.1 log10
      copies/mL; 184 (29%) were WHO Stage 3 or 4.Seventy one (11%) of these 625 women
      experienced SCR. Baseline factors independently associated with increased odds of
      SCR included older age, lower HIV-1 RNA, positive Hepatitis B surface antigen,
      and site location. At 96 weeks, only 6% of the SCR group had CD4 >= 350 cells/MUL
      compared with 67% in the non SCR group. CONCLUSION: After starting HAART, 11% of
      women with virologic suppression through 48 weeks experienced SCR. These patients
      were also less likely to achieve CD4 >= 350 cells/MUL by 96 weeks. The underlying
      causes and long term clinical implications of SCR deserve further investigation.
      TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00089505.

PMID- 24938529
TI  - Quality of reporting of randomised controlled trials of acupuncture for
      neurological diseases conducted in China.
AB  - OBJECTIVES: To investigate the quality of reporting for randomised controlled
      trials of acupuncture for neurological disorders conducted in China before and
      after the implementation of the Consolidated Standards of Reporting Trials
      (CONSORT) and Standards for Reporting Interventions in Controlled Trials of
      Acupuncture (STRICTA) guidelines. METHODS: The quality of reporting for included
      papers was assessed against a subset of criteria adapted from CONSORT and
      STRICTA. CONSORT and STRICTA were developed in 1996 and 2001, respectively. Thus,
      for the date of publication we selected 2-year periods, at 5-yearly intervals:
      1994-1995; 1999-2000; 2004-2005 and 2009-2010. These selections cover the periods
      before the publication dates of both guidelines (1996, 2001) and at least 3 years
      afterwards, and provide reasonably up-to-date data. We calculated the total score
      for each guideline and compared reported differences during different date
      ranges. RESULTS: For CONSORT items (maximum score 8), there was evidence of a
      slight improvement in reporting between 1994-1995 and 1999-2000 combined (2.5+/
      0.6) and 2004-2005 and 2009-2010 combined (3.0+/-0.9) (difference 0.5, 95% CI 0.2
      to 0.8). For STRICTA items (maximum score 17), there was evidence of a slight
      improvement in reporting between 1994-1995 and 1999-2000 combined (8.9+/-1.8) and
      2004-2005 and 2009-2010 combined (10.3+/-1.6) (difference 1.4, 95% CI 0.9 to
      1.9). CONCLUSIONS: The quality of reporting for studies of acupuncture for
      neurological disorders has generally improved since the implementation of STRICTA
      and CONSORT guidelines.

PMID- 24938530
TI  - Motion patterns in acupuncture needle manipulation.
AB  - BACKGROUND: In clinical practice, acupuncture manipulation is highly
      individualised for each practitioner. Before we establish a standard for
      acupuncture manipulation, it is important to understand completely the
      manifestations of acupuncture manipulation in the actual clinic. To examine
      motion patterns during acupuncture manipulation, we generated a fitted model of
      practitioners' motion patterns and evaluated their consistencies in acupuncture
      manipulation. METHODS: Using a motion sensor, we obtained real-time motion data
      from eight experienced practitioners while they conducted acupuncture
      manipulation using their own techniques. We calculated the average amplitude and
      duration of a sampled motion unit for each practitioner and, after normalisation,
      we generated a true regression curve of motion patterns for each practitioner
      using a generalised additive mixed modelling (GAMM). RESULTS: We observed
      significant differences in rotation amplitude and duration in motion samples
      among practitioners. GAMM showed marked variations in average regression curves
      of motion patterns among practitioners but there was strong consistency in motion
      parameters for individual practitioners. The fitted regression model showed that
      the true regression curve accounted for an average of 50.2% of variance in the
      motion pattern for each practitioner. CONCLUSIONS: Our findings suggest that
      there is great inter-individual variability between practitioners, but remarkable
      intra-individual consistency within each practitioner.

PMID- 24938531
TI  - Copper deficiency.

PMID- 24938532
TI  - Synthesis of microcrystals of the [Fe(L)(bipy)] spin crossover coordination
      polymer in a poly-4-vinylpyridine matrix.
AB  - Microcrystals of the spin-crossover coordination polymer [FeL(bipy)] (L=[3,3']
      [1,2-phenylenebis(iminoethylidyne)]bis-(2,4-pentanedionato)(2-), bipy=4,4'
      bipyridine) have been prepared in a poly(4-vinylpyridine) (P4VP) matrix. This was
      done by sequential addition of the iron(II) precursor complex and the bridging
      ligand bipy to a P4VP matrix, and by repetition of this cycle. The obtained
      composite material was characterized using TEM, SEM, XRPD, and SQUID
      measurements, and Mossbauer spectroscopy. With repeating cycles, the size of the
      [FeL(bipy)] crystals in the P4VP matrix increases from submicrometer to
      micrometer dimensions. A strong dependence on the number of cycles is observed.
      Above a critical size and concentration, the microcrystals show the same
      cooperative spin transition as the bulk material. No indication for a gradual
      spin transition is observed, but the remaining iron centers are either high-spin
      or low-spin depending on the coordination environment. 

PMID- 24938533
TI  - Population genetics for 17 Y-STR loci in a Chinese Han population sample from
      Mudanjiang city, Northeast China.

PMID- 24938535
TI  - Severe manifestations of extrapulmonary tuberculosis in HIV-infected children
      initiating antiretroviral therapy before 2 years of age.
AB  - BACKGROUND: Early initiation of antiretroviral therapy (ART) in HIV-infected
      infants reduces mortality and opportunistic infections including tuberculosis
      (TB). However, young HIV-infected children remain at high risk of TB disease
      following mycobacterial infection. We document the spectrum of TB disease in HIV
      infected children <2 years of age on ART. METHODS: Retrospective cohort study;
      records of children <2 years of age initiating routine ART at Tygerberg
      Children's Hospital, Cape Town, January 2003-December 2010 were reviewed.
      Clinical data at ART initiation (baseline) and TB episodes after ART initiation,
      to June 2012, were recorded. TB immune reconstitution syndrome (TB-IRIS) and
      incident TB were defined as TB diagnosed within 3 months, and >3 months after,
      ART initiation respectively. Baseline characteristics were compared in children
      with TB-IRIS and those with incident TB. RESULTS: In 494 children, median follow
      up time on ART was 10.7 months. Fifty-five TB treatment episodes occurred after
      ART initiation: 23 (42%) TB-IRIS (incidence 21.9/100 person years (py)) and 32
      (58%) incident TB (incidence 3.9/100 py). Children with TB-IRIS and those with
      incident TB had similar baseline characteristics. Eight of 10 cases of
      extrapulmonary TB were severe: 4 IRIS (2 meningitis, 1 disseminated, 1
      pericarditis) and 4 incident cases (1 each miliary, meningitis, pericarditis and
      spinal). Fifty-one children (10%) died (mortality rate 5.96/100 py). Starting ART
      at <1 year of age approached significance as a risk factor for TB-IRIS (adjusted
      OR (AOR) 8.64, p=0.06); weight-for-age Z score <-2 predicted death (AOR 6.37,
      p<0.001). CONCLUSIONS: Severe TB manifestations were observed among young HIV
      infected children on ART.

PMID- 24938536
TI  - Intravenous salbutamol for childhood asthma: evidence-based medicine?
AB  - Intravenous salbutamol is commonly used to treat children with severe asthma
      unresponsive to inhaled beta2-agonist therapy. However, in this setting, there is
      little clinical trial data demonstrating its effectiveness. Additionally, there
      are significant concerns that intravenous salbutamol-dosing recommendations for
      children with acute asthma are excessive, and unnecessarily raise the potential
      for adverse reactions, such as lactic acidosis and tachycardia which, by
      increasing respiratory workload, exacerbate respiratory failure. Here, we review
      salbutamol clinical pharmacology and toxicology, evidence relating to its use in
      acute asthma and highlight gaps in the evidence base. 

PMID- 24938538
TI  - A rare ovarian tumour in a 5-month-old infant.

PMID- 24938537
TI  - Use of high flow nasal cannula oxygen (HFNCO) in infants with bronchiolitis on a
      paediatric ward: a 3-year experience.

PMID- 24938534
TI  - Comparative effects of two different forms of selenium on oxidative stress
      biomarkers in healthy men: a randomized clinical trial.
AB  - Epidemiologic and laboratory studies indicate that dietary selenium protects
      against prostate cancer. Results from clinical trials suggest that selenium
      enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing
      prostate cancer risk. Our objectives were to directly compare for the first time
      the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We
      performed a randomized double blind, placebo-controlled trial of SY (200 or 285
      MUg/day) and SeMet (200 MUg/day) administered for 9 months in 69 healthy men.
      Primary endpoints included blood levels of selenium-containing compounds and
      oxidative stress biomarkers [urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso
      prostaglandin-F2alpha (8-iso-PGF2alpha) and blood glutathione (GSH)]. Secondary
      endpoints included plasma glucose and PSA levels. Compliance was high in all
      groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9
      months in SeMet and low- and high-dose SY groups, respectively, and returned to
      baseline levels after a 3-month washout (P < 0.05). Levels of 8-OHdG and 8-iso
      PGF2alpha were decreased 34% and 28%, respectively, after 9 months in the high
      dose SY group (P < 0.05). These decreases were greatest in individuals with low
      baseline plasma levels of selenium (<127 ng/mL). No changes in serum PSA or blood
      glucose and GSH were observed. Overall, we showed for the first time, reductions
      in biomarkers of oxidative stress following supplementation with SY but not SeMet
      in healthy men. These findings suggest that selenium-containing compounds other
      than SeMet may account for the decrease in oxidative stress.

PMID- 24938539
TI  - Government of the people, by the people, for the people: bioethics, literature,
      and method.

PMID- 24938540
TI  - Bioethics and literature: an exciting overlap.

PMID- 24938542
TI  - ESGAR 2014 Book of Abstracts.

PMID- 24938541
TI  - Sex determination by tooth size in a sample of Greek population.
AB  - Sex assessment from tooth measurements can be of major importance for forensic
      and bioarchaeological investigations, especially when only teeth or jaws are
      available. The purpose of this study is to assess the reliability and
      applicability of establishing sex identity in a sample of Greek population using
      the discriminant function proposed by Rosing et al. (1995). The study comprised
      of 172 dental casts derived from two private orthodontic clinics in Athens. The
      individuals were randomly selected and all had clear medical history. The
      mesiodistal crown diameters of all the teeth were measured apart from those of
      the 3rd molars. The values quoted for the sample to which the discriminant
      function was first applied were similar to those obtained for the Greek sample.
      The results of the preliminary statistical analysis did not support the use of
      the specific discriminant function for a reliable determination of sex by means
      of the mesiodistal diameter of the teeth. However, there was considerable
      variation between different populations and this might explain the reason for
      lack of discriminating power of the specific function in the Greek population. In
      order to investigate whether a better discriminant function could be obtained
      using the Greek data, separate discriminant function analysis was performed on
      the same teeth and a different equation emerged without, however, any real
      improvement in the classification process, with an overall correct classification
      of 72%. The results showed that there were a considerably higher percentage of
      females correctly classified than males. The results lead to the conclusion that
      the use of the mesiodistal diameter of teeth is not as a reliable method as one
      would have expected for determining sex of human remains from a forensic context.
      Therefore, this method could be used only in combination with other
      identification approaches. 

PMID- 24938543
TI  - Glucose reduces the anticonvulsant effects of the ketogenic diet in EL mice.
AB  - The ketogenic diet (KD) is known to be anticonvulsant and anti-epileptogenic.
      While the mechanism behind this therapeutic benefit is unclear, a reduction of
      circulating glucose levels through calorie restriction (CR) has been implicated.
      Foods or drinks that elevate blood glucose are known to compromise the
      therapeutic benefit of the KD in some children with epilepsy. We therefore
      evaluated the effect of a calorie restricted KD (KD-R) with supplementation of
      glucose in the drinking water of EL mice, a natural model of idiopathic
      generalized epilepsy, prior to seizure testing to assess the effect of glucose on
      seizure generation. Mice were fed either a standard diet or the KD unrestricted
      (SD-UR and KD-UR, respectively), or the KD restricted (KD-R). d-Glucose (25 mM)
      was supplemented in the drinking water of KD-R fed mice for 0.5h or for 2.5h
      prior to seizure testing. Each restricted mouse served as its own body weight
      control to achieve a 15-18% body weight reduction. Seizure susceptibility, body
      weights, and plasma glucose and beta-hydroxybutyrate levels were measured over a
      nine-week treatment period. Body weights and glucose levels remained high over
      the testing period in both the SD-UR and the KD-UR groups, but were significantly
      reduced in all R-fed groups. A significant increase in beta-hydroxybutyrate
      levels was observed in all KD groups. Seizure susceptibility remained highest in
      the SD-UR group, was slightly reduced in the KD-UR group, and was significantly
      reduced after three weeks in all R-fed groups. Supplementation of glucose prior
      to seizure testing resulted in a decrease of seizure threshold for R-fed mice,
      but did not alter bodyweight or circulating glucose levels. The KD has both an
      anticonvulsant and antiepileptogenic effect in EL mice. Here we confirm that CR
      enhances the anticonvulsant action of the KD in EL mice. Additionally, we show
      for the first time that supplementation of glucose decreases the anticonvulsant
      action of the KD, which further supports the hypothesis that CR works through
      transitioning metabolism from glucose to ketone utilization for energy.

PMID- 24938544
TI  - Immunohistochemistry comparing endoscopic vein harvesting vs. open vein
      harvesting on saphenous vein endothelium.
AB  - OBJECTIVE: The present study attempts to compare the immunohistochemistry (IHC)
      of von Willebrand factor (vWf) , endothelial cadherin, Caveolin and endothelial
      Nitric Oxide Synthase (eNOS) in VasoView Endoscopic Vein Harvesting (EVH) versus
      traditional Open Vein Harvesting (OVH) techniques for Coronary Artery Bypass
      Graft (CABG) Surgery performed in Javad al Aemeh Hospital of Mashhad, Iran in
      2013,. METHODS AND MATERIALS: Forty-seven patients were scheduled for CABG (30
      EVH and 17 OVH) among whom patients with relatively same gender and similar age
      were selected. Three separate two cm vein samples were harvested from each
      patient's saphenous vein. Each portion was collected from distal, middle and
      proximal zones of the saphenous vein. The tissues were deparaffinized, and
      antigen retrieval was done using EZ-retriever followed by an immunohistochemistry
      evaluation with vWf, e-cadherin, Caveolin and eNOS. In addition, demographic
      questioner as of Lipid profile, FBS, BMI, and cardiovascular risk factors were
      collected. Data analyses, including parametric and nonparametric tests were
      undertaken using the SPSS 16 software. A P value < 0.05 was regarded as
      statistically significant. RESULTS: The mean age of the EVH and OVH groups were
      63.76 +/- 9.51 and 63.63 +/- 8.31 years respectively with no significant
      difference between them (p = 0.989). In addition, there was no great difference
      between the EVH and OVH groups in lipid profile, DM, HTN, smoking history, CVA,
      and valvular dysfunction (P > 0.05). Qualitative report of vWf, e-cadherin,
      Caveolin and eNOS reveals no significant difference between the EVH and OVH (P >
      0.05). CONCLUSION: This study indicates that VasoView EVH technique causes no
      endothelial damage in comparison with OVH. This study could be a molecular
      confirmation for the innocuous of EVH technique.

PMID- 24938547
TI  - Black on red: Florence Arnold.

PMID- 24938548
TI  - Task force recommends screening high-risk individuals for hepatitis B infection.

PMID- 24938559
TI  - Management of comorbid diabetes mellitus and worsening heart failure.

PMID- 24938560
TI  - A piece of my mind. Keeping the pace.

PMID- 24938561
TI  - Thrombolytic therapy for pulmonary embolism.

PMID- 24938563
TI  - Association between tumor necrosis factor-alpha antagonists and risk of cancer in
      patients with inflammatory bowel disease.
AB  - IMPORTANCE: A Cochrane review and network meta-analysis concluded that there is
      need for more research on adverse effects, including cancer, after treatment with
      tumor necrosis factor alpha (TNF-alpha) antagonists and that national registries
      and large databases would provide relevant sources of data to evaluate these
      effects. OBJECTIVE: To investigate whether patients with inflammatory bowel
      disease (IBD) exposed to TNF-alpha antagonists were at increased risk of
      developing cancer. DESIGN, SETTING, AND PARTICIPANTS: Nationwide register-based
      cohort study in Denmark, 1999-2012. Participants were 56,146 patients 15 years or
      older with IBD identified in the National Patient Registry, of whom 4553 (8.1%)
      were exposed to TNF-alpha antagonists. Cancer cases were identified in the Danish
      Cancer Registry. MAIN OUTCOMES AND MEASURES: Rate ratios (RRs) for incident
      cancer (overall and site-specific) comparing TNF-alpha antagonist users and
      nonusers, estimated using Poisson regression adjusted for age, calendar year,
      disease duration, propensity scores, and use of other IBD medications. RESULTS:
      During 489,433 person-years of follow-up (median, 9.3 years [interquartile range,
      4.2-14.0]), 81 of 4553 patients exposed to TNF-alpha antagonists (1.8%) (median
      follow-up, 3.7 years [interquartile range, 1.8-6.0]) and 3465 of 51,593 unexposed
      patients (6.7%) developed cancer, yielding a fully adjusted RR of 1.07 (95% CI,
      0.85-1.36). There was no significantly increased risk of cancer in analyses
      according to time since first TNF-alpha antagonist exposure (less than 1 year:
      RR, 1.10 [95% CI, 0.67-1.81]; 1 to less than 2 years: RR, 1.22 [95% CI, 0.77
      1.93]; 2 to less than 5 years: RR, 0.82 [95% CI, 0.54-1.24]; 5 or more years: RR,
      1.33 [95% CI, 0.88-2.03]) and in analyses according to the number of TNF-alpha
      antagonist doses received (1 to 3 doses: RR, 1.02 [95% CI, 0.71-1.47]; 4 to 7
      doses: RR, 0.89 [95% CI, 0.55-1.42]; 8 or more doses: RR, 1.29 [95% CI, 0.90
      1.85]). No site-specific cancers were in significant excess in fully adjusted
      models. CONCLUSIONS AND RELEVANCE: In this Danish nationwide study, exposure to
      TNF-alpha antagonists among patients with IBD was not associated with an
      increased risk of cancer over a median follow-up of 3.7 years among those
      exposed. An increased risk associated with longer-term accumulated doses and
      follow-up cannot be excluded.

PMID- 24938562
TI  - Effect of selumetinib vs chemotherapy on progression-free survival in uveal
      melanoma: a randomized clinical trial.
AB  - IMPORTANCE: Uveal melanoma is characterized by mutations in GNAQ and GNA11,
      resulting in mitogen-activated protein kinase pathway activation. OBJECTIVE: To
      assess the efficacy of selumetinib, a selective, non-adenosine triphosphate
      competitive inhibitor of MEK1 and MEK2, in uveal melanoma. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized, open-label, phase 2 clinical trial comparing
      selumetinib vs chemotherapy conducted from August 2010 through December 2013
      among 120 patients with metastatic uveal melanoma at 15 academic oncology centers
      in the United States and Canada. INTERVENTIONS: One hundred one patients were
      randomized in a 1:1 ratio to receive selumetinib, 75 mg orally twice daily on a
      continual basis (n = 50), or chemotherapy (temozolomide, 150 mg/m2 orally daily
      for 5 of every 28 days, or dacarbazine, 1000 mg/m2 intravenously every 21 days
      [investigator choice]; n = 51) until disease progression, death, intolerable
      adverse effects, or withdrawal of consent. After primary outcome analysis, 19
      patients were registered and 18 treated with selumetinib without randomization to
      complete the planned 120-patient enrollment. Patients in the chemotherapy group
      could receive selumetinib at the time of radiographic progression. MAIN OUTCOMES
      AND MEASURES: Progression-free survival, the primary end point, was assessed as
      of April 22, 2013. Additional end points, including overall survival, response
      rate, and safety/toxicity, were assessed as of December 31, 2013. RESULTS: Median
      progression-free survival among patients randomized to chemotherapy was 7 weeks
      (95% CI, 4.3-8.4 weeks; median treatment duration, 8 weeks; interquartile range
      [IQR], 4.3-16 weeks) and among those randomized to selumetinib was 15.9 weeks
      (95% CI, 8.4-21.1 weeks; median treatment duration, 16.1 weeks; IQR, 8.1-25.3
      weeks) (hazard ratio, 0.46; 95% CI, 0.30-0.71; P < .001). Median overall survival
      time was 9.1 months (95% CI, 6.1-11.1 months) with chemotherapy and 11.8 months
      (95% CI, 9.8-15.7 months) with selumetinib (hazard ratio, 0.66; 95% CI, 0.41
      1.06; P = .09). No objective responses were observed with chemotherapy. Forty
      nine percent of patients treated with selumetinib achieved tumor regression, with
      14% achieving an objective radiographic response to therapy. Treatment-related
      adverse events were observed in 97% of patients treated with selumetinib, with
      37% requiring at least 1 dose reduction. CONCLUSIONS AND RELEVANCE: In this
      hypothesis-generating study of patients with advanced uveal melanoma, selumetinib
      compared with chemotherapy resulted in a modestly improved progression-free
      survival and response rate; however, no improvement in overall survival was
      observed. Improvement in clinical outcomes was accompanied by a high rate of
      adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01143402.

PMID- 24938564
TI  - Thrombolysis for pulmonary embolism and risk of all-cause mortality, major
      bleeding, and intracranial hemorrhage: a meta-analysis.
AB  - IMPORTANCE: Thrombolytic therapy may be beneficial in the treatment of some
      patients with pulmonary embolism. To date, no analysis has had adequate
      statistical power to determine whether thrombolytic therapy is associated with
      improved survival, compared with conventional anticoagulation. OBJECTIVE: To
      determine mortality benefits and bleeding risks associated with thrombolytic
      therapy compared with anticoagulation in acute pulmonary embolism, including the
      subset of hemodynamically stable patients with right ventricular dysfunction
      (intermediate-risk pulmonary embolism). DATA SOURCES: PubMed, the Cochrane
      Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception
      through April 10, 2014. STUDY SELECTION: Eligible studies were randomized
      clinical trials comparing thrombolytic therapy vs anticoagulant therapy in
      pulmonary embolism patients. Sixteen trials comprising 2115 individuals were
      identified. Eight trials comprising 1775 patients specified inclusion of patients
      with intermediate-risk pulmonary embolism. DATA EXTRACTION AND SYNTHESIS: Two
      reviewers independently extracted trial-level data including number of patients,
      patient characteristics, duration of follow-up, and outcomes. MAIN OUTCOMES AND
      MEASURES: The primary outcomes were all-cause mortality and major bleeding.
      Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage
      (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated
      using a fixed-effects model. RESULTS: Use of thrombolytics was associated with
      lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89%
      [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater
      risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42%
      [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78
      12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not
      significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50
      3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary
      embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT =
      54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated
      with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events
      (OR, 3.19; 95% CI, 2.07-4.92). CONCLUSIONS AND RELEVANCE: Among patients with
      pulmonary embolism, including those who were hemodynamically stable with right
      ventricular dysfunction, thrombolytic therapy was associated with lower rates of
      all-cause mortality and increased risks of major bleeding and ICH. However,
      findings may not apply to patients with pulmonary embolism who are
      hemodynamically stable without right ventricular dysfunction.

PMID- 24938566
TI  - Exercise for depression.
AB  - CLINICAL QUESTION: Is exercise an effective treatment for depression? BOTTOM
      LINE: Exercise is associated with a greater reduction in depression symptoms
      compared with no treatment, placebo, or active control interventions, such as
      relaxation or meditation. However, analysis of high-quality studies alone
      suggests only small benefits.

PMID- 24938565
TI  - Does this patient have an exudative pleural effusion? The Rational Clinical
      Examination systematic review.
AB  - IMPORTANCE: Thoracentesis is performed to identify the cause of a pleural
      effusion. Although generally safe, thoracentesis may be complicated by transient
      hypoxemia, bleeding, patient discomfort, reexpansion pulmonary edema, and
      pneumothorax. OBJECTIVE: To identify the best means for differentiating between
      transudative and exudative effusions and also to identify thoracentesis
      techniques for minimizing the risk of complications by performing a systematic
      review the evidence. DATA SOURCES: We searched The Cochrane Library, MEDLINE, and
      Embase from inception to February 2014 to identify relevant studies. STUDY
      SELECTION: We included randomized and observational studies of adult patients
      undergoing thoracentesis that examined diagnostic tests for differentiating
      exudates from transudates and evaluated thoracentesis techniques associated with
      a successful procedure with minimal complications. DATA EXTRACTION AND SYNTHESIS:
      Two investigators independently appraised study quality and extracted data from
      studies of laboratory diagnosis of pleural effusion for calculation of likelihood
      ratios (LRs; n = 48 studies) and factors affecting adverse event rates (n = 37
      studies). RESULTS: The diagnosis of an exudate was most accurate if cholesterol
      in the pleural fluid was greater than 55 mg/dL (LR range, 7.1-250), lactate
      dehydrogenase (LDH) was greater than 200 U/L (LR, 18; 95% CI, 6.8-46), or the
      ratio of pleural fluid cholesterol to serum cholesterol was greater than 0.3 (LR,
      14; 95% CI, 5.5-38). A diagnosis of exudate was less likely when all Light's
      criteria (a ratio of pleural fluid protein to serum protein >0.5, a ratio of
      pleural fluid LDH to serum LDH >0.6, or pleural fluid LDH >two-thirds the upper
      limit of normal for serum LDH) were absent (LR, 0.04; 95% CI, 0.02-0.11). The
      most common complication of thoracentesis was pneumothorax, which occurred in
      6.0% of cases (95% CI, 4.0%-7.0%). Chest tube placement was required in 2.0% of
      procedures (95% CI, 0.99%-2.9%) in which a patient was determined to have
      radiographic evidence of a pneumothorax. With ultrasound, a radiologist's marking
      the needle insertion site was not associated with decreased pneumothorax events
      (skin marking vs no skin marking odds ratio [OR], 0.37; 95% CI, 0.08-1.7). Use of
      ultrasound by any experienced practitioner also was not associated with decreased
      pneumothorax events (OR, 0.55; 95% CI, 0.06-5.3). CONCLUSIONS AND RELEVANCE:
      Light's criteria, cholesterol and pleural fluid LDH levels, and the pleural fluid
      cholesterol-to-serum ratio are the most accurate diagnostic indicators for
      pleural exudates. Ultrasound skin marking by a radiologist or ultrasound-guided
      thoracentesis were not associated with a decrease in pneumothorax events.

PMID- 24938567
TI  - Lung opacification.

PMID- 24938568
TI  - Changes in health and medical spending among young adults under health reform.

PMID- 24938569
TI  - Number of human papillomavirus vaccine doses and condyloma.

PMID- 24938570
TI  - Number of human papillomavirus vaccine doses and condyloma--reply.

PMID- 24938571
TI  - Home-based exercise and hip fracture rehabilitation.

PMID- 24938572
TI  - Home-based exercise and hip fracture rehabilitation--reply.

PMID- 24938573
TI  - Withdrawal of Personal Genome Service.

PMID- 24938574
TI  - Withdrawal of Personal Genome Service--reply.

PMID- 24938578
TI  - Landmarks in simple pleural effusions.

PMID- 24938579
TI  - JAMA patient page. Gastroesophageal reflux disease.

PMID- 24938580
TI  - Effect of tadalafil once daily on prostate blood flow and perfusion in men with
      lower urinary tract symptoms secondary to benign prostatic hyperplasia: a
      randomized, double-blind, multicenter, placebo-controlled trial.
AB  - OBJECTIVE: To assess effects of tadalafil vs placebo on prostatic blood flow
      measured by transrectal ultrasonography in men aged >=45 years with moderate-to
      severe benign prostatic hyperplasia-lower urinary tract symptoms. METHODS: After
      screening and washout, patients were randomized to placebo (n = 50) or tadalafil
      5 mg (n = 47) once daily for 8 weeks. Transrectal ultrasonography was performed
      at baseline, 4, and 8 weeks. The primary efficacy measure was the prostate
      transition zone (TZ) resistive index (RI). Secondary efficacy measures were RI in
      the peripheral zone and bladder neck, color pixel intensity (CPI), and color
      pixel density (CPD) in all 3 regions. Outcomes were assessed using mixed-model
      repeated-measures analyses. RESULTS: The overall treatment effect (tadalafil vs
      placebo) for the change from baseline through week 8 in prostate TZ RI was not
      statistically significant (least squares mean change: placebo, -0.01; tadalafil,
      0.00; P = .118), nor was the change from baseline in prostate TZ CPI (P = .564)
      or CPD (P = .592). Results were similar for all flow measures in prostate
      peripheral zone and bladder neck. The adverse event profile was consistent with
      previous studies with no new safety findings. CONCLUSION: Tadalafil for 8 weeks
      in men with BPH-LUTS did not result in detectable decreases in arterial RI or
      increases in CPI or CPD in the prostate or bladder neck. Detection of changes may
      not be possible because of already low baseline RI, insufficient sensitivity of
      techniques used, or may have been confounded by methodologic variability across
      sites. Alternatively, other possible mechanisms not assessed in this study may be
      more prominently involved.

PMID- 24938581
TI  - Editorial comment.

PMID- 24938582
TI  - Reply: To PMID 24938580.

PMID- 24938583
TI  - Elimination of central sleep apnea by cardiac valve replacement: a continuous
      follow-up study in patients with rheumatic valvular heart disease.
AB  - BACKGROUND: Recent studies have suggested that cardiac surgery may affect sleep
      disordered breathing (SDB) in chronic heart failure patients. However, the
      dynamic changes in sleep apnea and heart function after cardiac surgery and the
      mechanisms responsible for these changes remain unknown. METHODS: Patients with
      rheumatic valvular heart disease (RVHD) and SDB were enrolled and followed up at
      three, six and 12 months after cardiac valve replacement (CVR). Baseline and
      follow-up clinical data consisting of NYHA classification, 6min walk distance (6
      MWD), medications, echocardiography, electrocardiography, chest X-ray, arterial
      blood gas, lung-to-finger circulation time (LFCT), and sleep data were collected
      and evaluated. RESULTS: Twenty-four central sleep apnea (CSA) patients and 15
      obstructive sleep apnea (OSA) patients completed three follow-up assessments.
      Comparison of the baseline parameters between OSA patients and CSA patients
      showed that CSA patients had a worse baseline cardiac function assessed by higher
      NYHA class, shorter 6-MWD, larger left atrial diameter, longer LFCT, and enhanced
      chemosensitivity (higher pH and lower arterial carbon dioxide tension (PaCO2)). A
      continuous significant elevation in 6-MWD and left ventricular ejection fraction
      and decrease in NYHA class, plasma BNP, and left atrial diameter were found in
      both CSA and OSA patients. When comparing CSA and OSA patients, the CSA indices
      were remarkably reduced at month 3 post CVR and sustained throughout the trial,
      whereas there were no significant decreases in OSA index and hypopnea index. pH
      values and LFCT were markedly decreased and PaCO2 markedly increased in patients
      with CSA at the end of the third months following CVR. These changes were
      sustained until the end of the trial. CONCLUSIONS: CSA patients with RVHD had a
      worse baseline cardiac function, enhanced chemosensitivity and disordered
      hemodynamic as compared with OSA patients with RVHD. CSA were eliminated after
      CVR; however, there were no changes in OSA. The elimination of CSA, post CVR, is
      associated with the combined efficacies of improvement of cardiac function,
      normalized chemosensitivity, and stabilized hemodynamic.

PMID- 24938584
TI  - Validation study of REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK)
      in east China.
AB  - OBJECTIVE: To validate the REM Sleep Behavior Disorder (RBD) Questionnaire-Hong
      Kong (RBDQ-HK) in polysomnography (PSG)-confirmed RBD and non-RBD subjects, and
      to evaluate its usefulness in different clinical populations. METHODS: In total,
      325 subjects (115 RBD and 210 controls) from East China were enrolled. After
      patients had finished the structured interview, and completed the RBDQ-HK and
      video-PSG test, we evaluated the reliability of RBDQ-HK (areas under the curves
      (AUC), the best cut-off values, factor 2 of RBDQ-HK, and overall scale) and
      validated the usefulness of RBDQ-HK between the Parkinson disease (PD) and
      obstructive sleep apnea (OSA) groups. RESULTS: The best cut-off values for factor
      2 of RBDQ-HK were located at 7/8 with a sensitivity of 90% and specificity of 82%
      (AUC=0.911), and for RBDQ-HK overall scale were located at 17 with a sensitivity
      of 85% and specificity of 81% (AUC=0.892) in all subjects. Both factor 2 and
      overall scale of RBDQ-HK are valid in all subjects (PD and OSA patients), with a
      higher accuracy given by factor 2 of RBDQ-HK. CONCLUSIONS: RBDQ-HK and its factor
      2 are useful and validated RBD screening instruments, and could be used as a tool
      for screening RBD in patients with PD and OSA.

PMID- 24938586
TI  - Novel strategies to improve early outcomes following total knee arthroplasty: a
      case control study of intra articular injection versus femoral nerve block.
AB  - PURPOSE: The incidence of total joint arthroplasty is rapidly increasing. As
      costs are rising as well, orthopaedic surgeons are now being called on to
      demonstrate the value of our procedures. We recently evaluated a new technique of
      local injection in total knee arthroplasty (TKA) as a potential means to improve
      quality and decrease costs. METHODS: A case-control study was performed. One
      hundred patients were prospectively studied receiving a novel local injection
      using liposomal bupivicaine in TKA. These were compared to a historical cohort of
      100 patients receiving a femoral nerve catheter. RESULTS: We found that patients
      receiving liposomal bupivicaine had improved pain scores, shorter lengths of
      stay, slightly less opioid intake, and large decreases in costs. CONCLUSION:
      Local injection in TKA with liposomal bupivicaine appears to be a useful tool in
      adding value to patient care. This technique was shown to improve patient
      outcomes while simultaneously decreasing costs.

PMID- 24938587
TI  - Sexual attraction and psychological adjustment in Dutch adolescents: coping style
      as a mediator.
AB  - This study examined whether feelings of same-sex attraction (SSA) in 12- to 15
      year-old Dutch adolescents were related to psychological health (self-esteem and
      psychological distress) and whether this relation was mediated by coping styles
      and moderated by biological sex. Data were collected from 1,546 high school
      students (802 boys and 744 girls; M age = 13.57 years) by means of standardized
      measurements. SSA was found to predict lower levels of self-esteem and higher
      levels of psychological distress. Further analyses showed that passive coping
      style partly mediated these associations. This mediation was not moderated by
      biological sex. The findings suggest that in understanding and addressing mental
      health disparities between sexual minorities and heterosexual youth attention
      should be paid to intrapersonal psychological factors such as coping styles.

PMID- 24938588
TI  - Why can't pedophilic disorder remit?

PMID- 24938585
TI  - Parkinson's disease and REM sleep behavior disorder result in increased non-motor
      symptoms.
AB  - OBJECTIVE: Rapid eye movement (REM)-sleep behavior disorder (RBD) is often
      comorbid with Parkinson's disease (PD). The current study aimed to provide a
      detailed understanding of the impact of having RBD on multiple non-motor symptoms
      (NMS) in patients with PD. METHODS: A total of 86 participants were evaluated for
      RBD and assessed for multiple NMS of PD. Principal component analysis was
      utilized to model multiple measures of NMS in PD, and a multivariate analysis of
      variance was used to assess the relationship between RBD and the multiple NMS
      measures. Seven NMS measures were assessed: cognition, quality of life, fatigue,
      sleepiness, overall sleep, mood, and overall NMS of PD. RESULTS: Among the PD
      patients, 36 were classified as having RBD (objective polysomnography and
      subjective findings), 26 as not having RBD (neither objective nor subjective
      findings), and 24 as probably having RBD (either subjective or objective
      findings). RBD was a significant predictor of increased NMS in PD while
      controlling for dopaminergic therapy and age (p=0.01). The RBD group reported
      more NMS of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and
      overall NMS (p=0.002). CONCLUSION: In PD, RBD is associated with more NMS,
      particularly increased depressive symptoms, sleep disturbances, and fatigue. More
      research is needed to assess whether PD patients with RBD represent a subtype of
      PD with different disease progression and phenomenological presentation.

PMID- 24938589
TI  - On the definition of female sexual interest/arousal disorder.

PMID- 24938591
TI  - Efficiency of radiation protection equipment in interventional radiology: a
      systematic Monte Carlo study of eye lens and whole body doses.
AB  - Monte Carlo calculations were used to investigate the efficiency of radiation
      protection equipment in reducing eye and whole body doses during fluoroscopically
      guided interventional procedures. Eye lens doses were determined considering
      different models of eyewear with various shapes, sizes and lead thickness. The
      origin of scattered radiation reaching the eyes was also assessed to explain the
      variation in the protection efficiency of the different eyewear models with
      exposure conditions. The work also investigates the variation of eye and whole
      body doses with ceiling-suspended shields of various shapes and positioning. For
      all simulations, a broad spectrum of configurations typical for most
      interventional procedures was considered. Calculations showed that 'wrap around'
      glasses are the most efficient eyewear models reducing, on average, the dose by
      74% and 21% for the left and right eyes respectively. The air gap between the
      glasses and the eyes was found to be the primary source of scattered radiation
      reaching the eyes. The ceiling-suspended screens were more efficient when
      positioned close to the patient's skin and to the x-ray field. With the use of
      such shields, the Hp(10) values recorded at the collar, chest and waist level and
      the Hp(3) values for both eyes were reduced on average by 47%, 37%, 20% and 56%
      respectively. Finally, simulations proved that beam quality and lead thickness
      have little influence on eye dose while beam projection, the position and head
      orientation of the operator as well as the distance between the image detector
      and the patient are key parameters affecting eye and whole body doses. 

PMID- 24938590
TI  - Colorectal cancer of the elderly.
AB  - OPINION STATEMENT: Colorectal cancer (CRC) disproportionately affects the
      elderly. Older age is a strong risk factor for both the development of
      precancerous adenomas and CRC, thus raising the issue of screening and
      surveillance in older patients. However, screening and surveillance decisions in
      the elderly can be complex and challenging. Elderly patients are a diverse and
      heterogeneous group and special considerations such as co-morbid medical
      conditions, functional status, and cognitive ability play a role in one's
      decisions regarding the utility of screening and surveillance. Such
      considerations also play a role in factors related to screening modalities, such
      as colonoscopy, as well as CRC treatment options and regimens. This review
      addresses many of the unique factors associated with CRC of the elderly and
      critically examines many of the controversies and challenges surrounding CRC in
      older patients.

PMID- 24938592
TI  - Self-assembled capsules based on tetrafunctionalized calix[4]resorcinarene
      cavitands.
AB  - Calix[4]resorcinarene-based cavitands with a bowl-shaped aromatic cavity are
      widely used as scaffolds for covalently bound and self-assembled capsules. There
      are two main categories of calix[4]resorcinarene-based cavitands that are
      tetrafunctionalized at the upper (wider) rim: one category includes derivatives
      that have functionalized bridges between pairs of hydroxy groups of the
      calix[4]resorcinarene, and the second category includes derivatives with
      functional groups at the 2-position on the resorcinol ring and the methylene
      bridge between pairs of hydroxy groups. This review describes capsular self
      assemblies of the latter type of methylene-bridge cavitands, which are formed
      through hydrogen bonds, metal-coordination bonds, and dynamic covalent bonds. 

PMID- 24938593
TI  - Effect of nitrogen fertilisation and irrigation on phenolic content, phenolic
      acid composition, and antioxidant activity of winter wheat grain.
AB  - BACKGROUND: Understanding the variance of antioxidant in wheat grain responses to
      irrigation and nitrogen (N) fertiliser management will improve the nutrient
      quality of wheat grain. Four N rates (0, 180, 240, and 300 kg ha(-1)) combined
      with irrigation times (I0, no irrigation; I1, jointing time irrigation; I2,
      jointing + flowering time irrigation), were used to determine the effect of N
      fertilisation and irrigation on total phenolic content (TPC), phenolic acid
      composition, and antioxidant activity (AOA) of wheat grain. RESULTS: Irrigation,
      N fertilisation and their interactions had significant effect on TPC, total
      flavonoid content (TFC), AOA, p-coumaric acid (PCA), as well as vanillic acid
      (VA) and chlorogenic acid (CA). I1 N300 treatment had the highest TPC at
      Zhengzhou and Wenxian (1451.5 ug g(-1) and 1397.9 ug g(-1), respectively)
      location, while I1 N240 resulted in the highest TFC (0.75 mg g(-1)) and VA (19.77
      ug g(-1)) at Wenxian. TPC, TFC, AOA, ferulic acid (FA), PCA and VA increased with
      N application rate (from 180 to 300 kg N ha(-1)). CONCLUSION: An appropriate
      irrigation and N management improved antioxidant content and AOA in wheat grain.
      Generally, I1 N240 and I1 N300 treatment resulted in the higher TPC, TFC, AOA, as
      well as phenolic acid, i.e. FA and VA.

PMID- 24938594
TI  - Is plasma C3 and C4 levels useful in young cerebral ischemic stroke patients?
      Associations with prognosis at 3 months.
AB  - Plasma complement C3 and C4 act as risk factor for vascular diseases related to
      atherosclerosis. The association C3 and C4 levels in young ischemic stroke
      patients with the prognosis were still not unknown. We conducted this study to
      establish the significance of admission C3 and C4 levels as a possible predictor
      of 3 months prognosis in young patients with acute ischemic stroke. We conducted
      this study in 1,451 young Chinese patients as determined by the modified Rankin
      Scale at 3 months. Bivariate logistic regression analyses were used to determine
      the risk factors of outcome in male and female patients. Stepwise logistic
      regression analysis confirmed only the lowest quartile of C3 level (0.17-0.90
      g/L) was independently associated with prognosis in male patient after adjustment
      the confounding risk factors of stroke [0.558 (0.382-0.815); P = 0.003], but not
      the association for plasma C4 levels. Meanwhile, serum SUA and WBC
      concentrations, TIA history are typically related to prognosis at 3 months after
      acute ischemic stroke. Our analysis does provide compelling information regarding
      the baseline complement C3 levels in young ischemic stroke patients as possible
      predictors of early prognosis after 3 months of acute phase. Thus, our results
      must be seen as a hypothesis only and will have to be confirmed in larger trials.

PMID- 24938595
TI  - The stoichiometry of scaffold complexes in living neurons - DLC2 functions as a
      dimerization engine for GKAP.
AB  - Quantitative spatio-temporal characterization of protein interactions in living
      cells remains a major challenge facing modern biology. We have investigated in
      living neurons the spatial dependence of the stoichiometry of interactions
      between two core proteins of the N-methyl-D-aspartate (NMDA)-receptor-associated
      scaffolding complex, GKAP (also known as DLGAP1) and DLC2 (also known as DYNLL2),
      using a novel variation of fluorescence fluctuation microscopy called two-photon
      scanning number and brightness (sN&B). We found that dimerization of DLC2 was
      required for its interaction with GKAP, which, in turn, potentiated GKAP self
      association. In the dendritic shaft, the DLC2-GKAP hetero-oligomeric complexes
      were composed mainly of two DLC2 and two GKAP monomers, whereas, in spines, the
      hetero-complexes were much larger, with an average of ~16 DLC2 and ~13 GKAP
      monomers. Disruption of the GKAP-DLC2 interaction strongly destabilized the
      oligomers, decreasing the spine-preferential localization of GKAP and inhibiting
      NMDA receptor activity. Hence, DLC2 serves a hub function in the control of
      glutamatergic transmission by ordering GKAP-containing complexes in dendritic
      spines. Beyond illuminating the role of DLC2-GKAP interactions in glutamatergic
      signaling, these data underscore the power of the sN&B approach for quantitative
      spatio-temporal imaging of other important protein complexes. 

PMID- 24938597
TI  - Procentriole assembly without centriole disengagement - a paradox of male
      gametogenesis.
AB  - Disengagement of parent centrioles represents the licensing process to restrict
      centriole duplication exactly once during the cell cycle. However, we provide
      compelling evidence that this general rule is overridden in insect gametogenesis,
      when distinct procentrioles are generated during prophase of the first meiosis
      while parent centrioles are still engaged. Moreover, the number of procentrioles
      increases during the following meiotic divisions, and up to four procentrioles
      were found at the base of each mother centriole. However, procentrioles fail to
      organize a complete set of A-tubules and are thus unable to function as a
      template for centriole formation. Such a system, in which procentrioles form but
      halt growth, represents a unique model to analyze the process of cartwheel
      assembly and procentriole formation. 

PMID- 24938598
TI  - Application of mathematical modeling in sustained release delivery systems.
AB  - INTRODUCTION: This review, presenting as starting point the concept of the
      mathematical modeling, is aimed at the physical and mathematical description of
      the most important mechanisms regulating drug delivery from matrix systems. The
      precise knowledge of the delivery mechanisms allows us to set up powerful
      mathematical models which, in turn, are essential for the design and optimization
      of appropriate drug delivery systems. AREAS COVERED: The fundamental mechanisms
      for drug delivery from matrices are represented by drug diffusion, matrix
      swelling, matrix erosion, drug dissolution with possible recrystallization (e.g.,
      as in the case of amorphous and nanocrystalline drugs), initial drug distribution
      inside the matrix, matrix geometry, matrix size distribution (in the case of
      spherical matrices of different diameter) and osmotic pressure. Depending on
      matrix characteristics, the above-reported variables may play a different role in
      drug delivery; thus the mathematical model needs to be built solely on the most
      relevant mechanisms of the particular matrix considered. EXPERT OPINION: Despite
      the somewhat diffident behavior of the industrial world, in the light of the most
      recent findings, we believe that mathematical modeling may have a tremendous
      potential impact in the pharmaceutical field. We do believe that mathematical
      modeling will be more and more important in the future especially in the light of
      the rapid advent of personalized medicine, a novel therapeutic approach intended
      to treat each single patient instead of the 'average' patient.

PMID- 24938599
TI  - Effect of phytosterols on rumen fermentation in vitro.
AB  - We investigated the effect of phytosterols on rumen fermentation in vitro using
      gas syringes as incubators. Phytosterols were dissolved in ethyl acetate (8.3%)
      and added at various concentrations to the common diet in rumen fluid. In vitro
      gas production (GP) was recorded after 3, 6, 12, 18, and 24 h incubation.
      Incubation was stopped at 6, 12, and 24 h and the inoculants were then tested for
      pH, dry matter digestibility (DMD), microbial protein yield (MCP), lactic acid,
      NH3-N, and volatile fatty acids (VFAs). GP was consistently higher than the
      control; particularly, treatments at 12, 18, and 24 h reached extremely
      significant levels (P < 0.01). Compared to the control group, the pH of ruminal
      fluid was slightly lower after incubation, and DMD and MCP increased with
      increasing phytosterol level except for the content of MCP at 6 h, which changed
      only minimally. Lactate was significantly lower after treatment compared to the
      control at 12 h (P < 0.01) and 24 h (P < 0.05), while NH3-N at 12 h (P < 0.05)
      and 24 h (P < 0.01) after treatment decreased significantly. Acetate, propionate,
      butyrate, and total VFA for all treatments were higher than those of the control,
      particularly for butyrate at 6 h (P < 0.01). These results suggest that
      phytosterols modify rumen fermentation by inhibiting released harmful products
      and promoting the release of beneficial product, which may be useful for
      improving nutrient utilization and animal health. 

PMID- 24938600
TI  - Association of BRCA2 variants with cardiovascular disease in Saudi Arabia.
AB  - Abnormalities in the breast cancer tumor suppressor genes (BRCA1 and BRCA2) are
      associated with breast and ovarian cancer. Recently, two single nucleotide
      polymorphisms (SNPs; rs11571836 and rs1799943) were identified, both located in
      untranslated regions of chromosome 13, associated with cardiovascular disease
      (CVD) in a multi-ethnic population. We examined the association between these
      BRCA2 polymorphisms and traits of CVD patients from Saudi Arabia. We genotyped
      rs11571836 and rs1799943 in 159 unrelated CVD patients and 176 healthy controls.
      The genotype and allele distributions in the overall population revealed a
      statistically significant association between rs1799943 and CVD (P = 0.01-0.022),
      whereas no risk association was identified for rs11571836. Additionally,
      haplotype analysis using both SNPs demonstrated no association between the SNPs
      and CVD. The genotype distribution of the 2 SNPs in the normal Saudi population
      deviated significantly (P < 0.000001) from that of the 6 different HapMap
      populations (CEU, CHB-Han, JPT, YRI, GIH, and MKK), except for the JPT population
      for rs1799943. This is the first study to examine the association between these
      SNPs and CVD in a Saudi population. Our results suggest that the increased health
      risk associated with the rs11571836 genotype is specific to male patients
      suffering from CVD. Stratification of patients and controls based on gender
      revealed no association between rs1799943 and the risk of CVD in either gender.
      These SNPs should be evaluated in larger cohorts in different populations to
      determine their suitability as screening markers for predicting CVD risk earlier
      in life to implement necessary preventive measures. 

PMID- 24938596
TI  - Phosphorylation of nucleoporin Tpr governs its differential localization and is
      required for its mitotic function.
AB  - A major constituent of the nuclear basket region of the nuclear pore complex
      (NPC), nucleoporin Tpr, plays roles in regulating multiple important processes.
      We have previously established that Tpr is phosphorylated in both a MAP-kinase
      dependent and MAP-kinase-independent manner, and that Tpr acts as both a
      substrate and as a scaffold for ERK2 (also known as MAPK1). Here, we report the
      identification of S2059 and S2094 as the major novel ERK-independent
      phosphorylation sites and T1677, S2020, S2023 and S2034 as additional ERK
      independent phosphorylation sites found in the Tpr protein in vivo. Our results
      suggest that protein kinase A phosphorylates the S2094 residue and that the site
      is hyperphosphorylated during mitosis. Furthermore, we find that Tpr is
      phosphorylated at the S2059 residue by CDK1 and the phosphorylated form
      distinctly localizes with chromatin during telophase. Abrogation of S2059
      phosphorylation abolishes the interaction of Tpr with Mad1, thus compromising the
      localization of both Mad1 and Mad2 proteins, resulting in cell cycle defects. The
      identification of novel phosphorylation sites on Tpr and the observations
      presented in this study allow better understanding of Tpr functions. 

PMID- 24938601
TI  - Cytogenetic and molecular identification of a wheat-Leymus mollis alien multiple
      substitution line from octoploid Tritileymus x Triticum durum.
AB  - Leymus mollis (Trin.) Pilger (NsNsXmXm, 2n = 28), a wild relative of common
      wheat, possesses many traits that are potentially valuable for wheat improvement.
      In order to exploit and utilize the useful genes of L. mollis, we developed a
      multiple alien substitution line, 10DM50, from the progenies of octoploid
      Tritileymus M842-16 x Triticum durum cv. D4286. Genomic in situ hybridization
      analysis of mitosis and meiosis (metaphase I), using labeled total DNA of
      Psathyrostachys huashanica as probe, showed that the substitution line 10DM50 was
      a cytogenetically stable alien substitution line with 36 chromosomes from wheat
      and three pairs of Ns genome chromosomes from L. mollis. Simple sequence repeat
      analysis showed that the chromosomes 3D, 6D, and 7D were absent in 10DM50.
      Expressed sequence tag-sequence tagged sites analysis showed that new chromatin
      from 3Ns, 6Ns, and 7Ns of L. mollis were detected in 10DM50. We deduced that the
      substitution line 10DM50 was a multiple alien substitution line with the 3D, 6D,
      and 7D chromosomes replaced by 3Ns, 6Ns, and 7Ns from L. mollis. 10DM50 showed
      high resistance to leaf rust and significantly improved spike length, spikes per
      plant, and kernels per spike, which are correlated with higher wheat yield. These
      results suggest that line 10DM50 could be used as intermediate material for
      transferring desirable traits from L. mollis into common wheat in breeding
      programs. 

PMID- 24938602
TI  - Identification of spliced mRNA isoforms of retinoid X receptor (RXR) in the
      Oriental freshwater prawn Macrobrachium nipponense.
AB  - Retinoid X receptors (RXR) are members of the nuclear receptor family that are
      conserved from invertebrates to vertebrates, and they play an essential role in
      regulating reproductive maturation, molting, and embryo development. In this
      study, five RXR isoforms, named RXRL2 (L, long form), RXRL3, RXRS1 (S, short
      form), RXRS2, and RXRS3, containing six domains from A to F, were cloned from the
      prawn Macrobrachium nipponense using 5'- and 3'- rapid amplification of cDNA
      ends. Differences among their structures were observed not only in the D and E
      domains but also in the A/B domain, which were previously found in insects but
      not in crustaceans. This is the first report to show that differences occur in
      the A/B domain of RXR in crustaceans. RXR expressions were also examined in
      various tissues including the ovary, testis, muscle, hepatopancreas, heart, gill,
      stomach, intestine, and cuticle. Expression pattern investigations indicated that
      the five isoforms were differentially expressed. RXRS3 was only detected in the
      ovary, and the other RXRs were abundant in the ovary and testis. These data
      suggested that RXR mediates a series of processes related to reproduction.

PMID- 24938603
TI  - Mapping of quantitative trait loci for the bolting trait in Brassica rapa under
      vernalizing conditions.
AB  - Premature bolting can occur occasionally during spring cultivation of heading
      Chinese cabbage in East Asia when the plants encounter low temperatures
      (vernalization), leading to economic loss. Breeding bolting-resistant cultivars
      is the best choice for solving this problem. We looked for QTLs responsible for
      varietal differences in the bolting trait in Brassica rapa under environmental
      conditions that promote vernalization. To achieve this goal, we constructed a
      linkage map with 107 simple sequence repeats and 54 insertion/deletion markers
      based on a segregating population of 186 F2 individuals. The resulting map
      consisted of 10 linkage groups and covered a total length of 947.1 cM, with an
      average genetic distance of 5.84 cM between adjacent markers. QTL analysis of the
      bolting trait was performed by two phenotypic evaluations (bolting index and
      flowering time) based on the scores in an F2 population in the spring of 2010,
      and scores in F2:3 families in autumn 2010 and spring 2011, respectively. Twenty
      six QTLs that controlled bolting were detected, accounting for 2.6 to 31.2% of
      the phenotypic variance. The detected QTLs with large effects co-localized mainly
      on linkage groups A02, A06, and A07. These QTLs may provide useful information
      for marker-assisted selection in a breeding program for late bolting or bolting
      resistant cultivars in B. rapa crops. 

PMID- 24938604
TI  - Expression of RUNX3 gene in pancreatic adenocarcinoma and its clinical
      significance.
AB  - We investigated the clinical significance of RUNX3 gene expression in human
      pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of
      pancreatic cancer tissues and paracancerous tissues were collected. RUNX3
      expression was detected by real-time PCR and immunohistochemistry. The
      relationships between clinicopathological findings and the expression of RUNX3
      were analyzed. The relative quantification level of RUNX3 mRNA expression in
      human pancreatic carcinoma tissues and paracancerous tissues was 2.60 (0.42
      12.82) and 1.02 (0.19-3.58), respectively (P < 0.05). The percentage of positive
      cells expressing RUNX3 protein in human pancreatic tissues and paracancerous
      tissues was 45.5 +/- 26.2 and 6.9 +/- 6.0%, respectively (P < 0.01). The high
      RUNX3 group (N = 9) with 45.5% or more of the cancer cells staining for RUNX3 and
      the low RUNX3 group (N = 21) with less than 45.5% cancer cells staining for
      RUNX3. Low expression of RUNX3 correlated significantly with an advanced TNM
      stage (chi(2) = 6.897, P = 0.045), lymph node metastasis (chi(2) = 4.739, P =
      0.029) and neural invasion (chi(2) = 5.44, P = 0.020). On the other hand, no
      association could be found between RUNX3 expression and clinicopathological
      variables including age, gender, tumor location, tumor size, tumor
      differentiation or the serum concentration of CEA and CA199. The expression of
      RUNX3 in pancreatic cancer tissues was obviously higher than that in the
      paracancerous tissues. Low expression of RUNX3 may have an important role in
      aggressiveness, lymph node metastasis and neural invasion in pancreatic cancer.
      In pancreatic carcinoma tissues, low expression of RUNX3 may indicate a poor
      prognosis. 

PMID- 24938605
TI  - Novel method to establish molecular identity using inter-simple sequence repeat
      markers in cotton (Gossypium hirsutum) cultivars.
AB  - Plant molecular identity (ID) is used to describe molecular characteristics of
      plants, which should contain all of the necessary information. Using inter-simple
      sequence repeat (ISSR) primers, molecular ID can be described in a way that
      reflects the polymerase chain reaction (PCR) conditions, annealing temperature,
      and the bands obtained in PCR amplification. A new complete molecular ID system
      is described in this study, which can be easily used and expanded to include more
      information. Using three cotton cultivars, we analyzed the products of PCR with
      ISSR primers and discussed the strategy for establishing their molecular ID.
      Using the segmented naming method, we designate the simple names and the full
      name systems of these three cultivars. 

PMID- 24938606
TI  - Analysis of cell cycle shortening and developmental interruption in Dictyostelium
      discoideum allC RNAi mutants.
AB  - Dictyostelium discoideum allC RNAi mutant cells are motile and aggregate
      together, but do not undergo further morphological development. The relatively
      quick growth rate of allC RNAi mutants compared to wild-type D. discoideum
      results in a shortened mutant cell cycle. However, at present, little is known
      about the mechanism underlying this phenomenon. Here, we used semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative
      RT-PCR, two-dimensional gel electrophoresis, and mass spectrometry/mass
      spectrometry to elucidate the phenomenon. We found significant downregulation of
      myosin II heavy chain, D. discoideum calcium-dependent cell adhesion molecule-1
      (DdCAD-1) mRNA, DdCAD-1 protein, D. discoideum mRNA for 14-3-3 and 14-3-3
      protein, and type A von Willebrand factor domain-containing protein mRNA in allC
      RNAi mutants. The results suggest that downregulation of the myosin II heavy
      chain could be one of key factors causing the developmental interruption and that
      downregulation of the 14-3-3 protein and the type A von Willebrand factor domain
      containing protein mRNA plays an important role in shortening the cell cycle of
      allC RNAi mutants. 

PMID- 24938607
TI  - Polymorphic microsatellite loci isolated from Cervus unicolor (Cervidae) show
      inbreeding in a domesticated population of Taiwan Sambar deer.
AB  - Primers for eight microsatellites were developed; they successfully amplified DNA
      from 20 domesticated Formosan Sambar deer (Cervus unicolor swinhoei). All loci
      were polymorphic, with 10-19 alleles per locus. The average observed
      heterozygosity across loci and samples was 0.310, ranging from 0 to 0.750 at each
      locus. All loci but one, CU18, deviated from Hardy-Weinberg equilibrium due to
      excessive homozygosity in these domesticated broodstocks, reflecting inbreeding.
      These microsatellite loci will be useful, not only for assessment of population
      structure and genetic variability, but also for conservation of wild deer
      populations in Taiwan. 

PMID- 24938608
TI  - A new reliable reference gene UBA52 for quantitative real-time polymerase chain
      reaction studies in pyloric cecal tissues of the starfish Asterias rubens.
AB  - The starfish Asterias rubens is one of the most abundant echinoderm species in
      the White, Barents, North, and Baltic Seas. This species is an important
      component of marine ecosystems and a model object for certain biological studies,
      in particular those requiring quantitative estimation of gene expression. As a
      rule, expression at the transcriptional level is estimated by real-time qPCR
      using the DeltaDeltaCt method, which allows the comparison of the copy number of
      target gene transcripts in samples with unknown mRNA/cDNA concentration.
      Application of this method requires normalization of the results relative to
      genes with stable expression levels (reference genes). The identification of
      reference genes is still a challenging task since data of this kind are missing
      for certain taxa, whereas the use of "standard" endogenous control genes without
      additional tests might lead to erroneous conclusions. We performed a preliminary
      analysis of the expression of many housekeeping genes in the pyloric ceca of A.
      rubens by high-throughput sequencing under normal and heat shock conditions. For
      one of them, the ubiquitin gene UBA52, low variation of expression (not greater
      than 2-fold) was shown using real-time qPCR. Tissues of pyloric ceca of normal
      adults and underyearlings and of adults after heat shock were used. The data
      obtained suggest that the UBA52 gene may be used as reference for normalization
      of gene expression at the mRNA level in the starfish A. rubens and probably in
      closely related species. 

PMID- 24938609
TI  - In vitro cytotoxicity screening of wild plant extracts from Saudi Arabia on human
      breast adenocarcinoma cells.
AB  - This study investigated the in vitro anticancer activities of a total of 14 wild
      angiosperms collected in Saudi Arabia. The cytotoxic activity of each extract was
      assessed against human breast adenocarcinoma (MCF-7) cell lines by using the MTT
      assay. Among the plants screened, the potential cytotoxic activity exhibited by
      the extract of Lavandula dentata (Lamiaceae) was identified, and we analyzed its
      anticancer potential by testing antiproliferative and apoptotic activity. Our
      results clearly show that ethanolic extract of L. dentata exhibits promising
      cytotoxic activity with an IC50 value of 39 MUg/mL. Analysis of cell
      morphological changes, DNA fragmentation and apoptosis (using an Annexin V assay)
      also confirmed the apoptotic effect of L. dentata extract, and thus, our data
      call for further investigations to determine the active chemical constituent(s)
      and their mechanisms of inducing apoptosis. 

PMID- 24938610
TI  - Roles of Fas/Fasl, Bcl-2/Bax, and Caspase-8 in rat nonalcoholic fatty liver
      disease pathogenesis.
AB  - The aim of this study was to investigate the roles of Fas/FasL, Bcl-2/Bax, and
      Caspase-8 mRNA expressions in nonalcoholic fatty liver disease (NAFLD). The
      apoptosis percentage was measured by flow cytometry, the immunohistochemical
      assay was performed for the determination of Fas, FasL, Bcl-2, and Bax
      expressions, and a real-time polymerase chain reaction (PCR) assay was performed
      to detect Caspase-8 mRNA expression. Flow cytometry showed that the apoptosis
      percentage of the rat liver in the experimental group increased, which increased
      more obviously with the extension of modeling time. Immunohistochemistry showed
      that with increasing hepatic steatosis, Fas and FasL protein staining intensified
      and the number of positive cells increased; the number of positive cells for Bcl
      2 and Bax gradually increased on the 4th, 8th, and 12th weeks in the experimental
      group, whereas the Bcl-2/Bax ratio decreased. The real-time PCR assay showed that
      Caspase-8 mRNA expression increased with increasing hepatic steatosis and
      inflammation, exhibiting a progressively rising trend. Hepatocyte apoptosis could
      promote NAFLD progression; Fas, FasL, and Caspase-8 mRNA activation were
      important contributing factors to NAFLD. The upregulation of Bax and Bcl-2
      expression might be one important mechanism of the apoptosis in NAFLD. 

PMID- 24938611
TI  - Quantative trait loci of seed traits for soybean in multiple environments.
AB  - Seed length and seed width are an important factor to the soybean yield. So the
      quantitative trait loci (QTL) location for seed length and seed width could
      assistant the breeding of soybean. In this study, the QTL underlying seed length
      and seed width were studied. A recombinant inbred line population of soybeans
      derived from a cross between the American semi-draft cultivars Charleston and
      Dongnong 594 were used in 7 environments. The quantitative trait loci underlying
      seed length, seed width, and seed length/seed width were analyzed by the method
      of composite interval mapping. Then, the epistatic effects and the QTL
      environment (QE) interaction effects were also analyzed. Some valuable QTL sites
      found had great effect to the seed trait. Results showed that 7 QTLs underlying
      seed length were identified mainly on linkage groups D1a, C2, B1, A1, G, and A2.
      For the seed width, 7 QTLs were identified on linkage groups D1a and O. Two QTLs
      of seed length/seed width were identified on linkage groups D1b and C2. No QE
      interaction was found for QTLs of seed length and seed width in 7 environments.
      QTLs of seed length/seed width on linkage groups A1 and I had a QE interaction in
      7 environments. Seven pairs of QTLs were identified that affected additive x
      additive epistatic effect of seed length, seed width, and seed length/seed width,
      which occurred among 8 linkage groups. These results supply a good foundation for
      molecular assistant breeding for soybean seed trait. 

PMID- 24938612
TI  - Expression of immune response genes in peripheral blood of cattle infested with
      Rhipicephalus microplus.
AB  - The bovine tick Rhipicephalus microplus is responsible for severe economic losses
      in tropical cattle production. Bos indicus breeds are more resistant to tick
      infestations than are Bos taurus breeds, and the understanding of the
      physiological mechanisms involved in this difference is important for the
      development of new methods of parasite control. We evaluated differences in the
      transcript expression of genes related to the immune response in the peripheral
      blood of cattle previously characterized as resistant or susceptible to tick
      infestation. Crossbreed F2 Gir x Holstein animals (resistant, N = 6; susceptible,
      N = 6) were artificially submitted to tick infestation. Blood samples were
      collected at 0, 24, and 48 h after tick infestation and evaluated for transcript
      expression of the CD25, CXCL8, CXCL10, FoxP3, interleukin (IL)-10, and tumor
      necrosis factor alpha (TNFalpha) genes. Gene expression of CD25 (6.00, P < 0.01),
      IL-10 (31.62, P < 0.01), FoxP3 (35.48, P < 0.01), and CXCL10 (3.38, P < 0.05) was
      altered in the resistant group at 48 h compared with samples collected before
      infestation. In the susceptible group, CXCL8 (-2.02, P < 0.05) and CXCL10 (2.20,
      P < 0.05) showed altered expression 24 h after infestation. CXCL8 (-5.78, P <
      0.05) also showed altered expression at 48 h after infestation when compared with
      samples collected before infestation. We detected a correlation between T
      gammadelta cell activity and the immunological mechanisms that result in a higher
      resistance to R. microplus in cattle. 

PMID- 24938613
TI  - Cloning and characterization of the drought-resistance OsRCI2-5 gene in rice
      (Oryza sativa L.).
AB  - The genomic expression profile of the super-hybrid rice Liangyoupeijiu female
      parent Pei'ai 64S in different tissues at different developmental stages under
      low temperature, drought, and high temperature stresses were detected using an
      Affymetrix GeneChip Rice Genome Array to screen upregulated and downregulated
      genes. In this study, we screened the drought-resistant gene OsRCI2-5, after
      which a constitutive OsRCI2-5 construct was created and transferred into
      Nipponbare. After polyethylene glycol-6000 and drought treatment, we found that
      the OsRCI2-5 gene improved the drought resistance of Nipponbare. Gene expression
      profiling showed that the OsRCI2-5 gene was expressed in the rice leaves, stems,
      and flower organs. Subcellular localization revealed that the gene was located in
      the membranes, and hence, we can deduce that a membrane signal peptide was
      responsible for signal transduction. 

PMID- 24938614
TI  - Motivational patterns as an instrument for predicting success in promising young
      football players.
AB  - Psychological characteristics are crucial to identifying talents, which is why
      these are being incorporated in today's multidimensional talent models. In
      addition to multidimensionality, talent studies are increasingly drawing on
      holistic theories of development, leading to the use of person-oriented
      approaches. The present study adopts such an approach by looking at the influence
      that motivational characteristics have on the development of performance, in a
      person-oriented way. For this purpose, it looks at how the constructs achievement
      motive, achievement goal orientation and self-determination interact with one
      another, what patterns they form and how these patterns are linked to subsequent
      sports success. Ninety-seven top young football players were questioned twice.
      Another year later, it was enquired which of these players had been selected for
      the U15 national team. At both measuring points, four patterns were identified,
      which displayed a high degree of structural and individual stability. As
      expected, the highly intrinsically achievement-oriented players were
      significantly more likely to move up into the U15 national team. The results
      point to the importance of favourable patterns of motivational variables in the
      form of specific types, for medium-term performance development among promising
      football talents, and thus provide valuable clues for the selection and promotion
      of those.

PMID- 24938616
TI  - [Female genital surgery, G-spot amplification techniques--state of the science].
AB  - The G-spot amplification is a process of "functional" intimate surgery consisting
      of a temporary physical increase of the size and sensitivity of the G-spot with a
      filler injected into the septum between the bladder and the vagina's anterior
      wall, in order to increase the frequency and importance of female orgasm during
      vaginal penetration. This surgical technique is based on the existence of an
      eponymous anatomical area described by Dr Grafenberg in 1950, responsible upon
      stimulation of systematic orgasm different from the clitoral orgasm, referring to
      the vaginal orgasm as described by Freud in 1905. The purpose of this article is
      to review the scientific basis of the G-spot, whose very existence is currently a
      debated topic, and to discuss the role of G-spot amplification surgery. 

PMID- 24938615
TI  - Partial mitigation of gold nanoparticle interactions with human lymphocytes by
      surface functionalization with a 'mixed matrix'.
AB  - AIM: To investigate interactions of gold nanoparticles with primary human
      lymphocytes and determine if the addition of a self-assembled monolayer of 'mixed
      matrix' ligands influenced these interactions. MATERIALS & METHODS: The effect of
      gold nanoparticles was measured by exposure to peripheral blood mononuclear cells
      (PBMCs) from healthy volunteers with subsequent examination of cell
      proliferation, cytokine secretion and CD4(+) T-cell activation relative to
      controls. RESULTS: Capped and as-synthesized gold nanoparticles augmented PBMC
      proliferation in response to phytohemagglutinin and this effect was greater for
      as-synthesized than for capped gold nanoparticles. Release of IL-10 and IFN-gamma
      from PBMCs was increased and the effect was again more marked for as-synthesized
      than capped gold nanoparticles. CONCLUSION: This method provides an ex vivo
      approach for studying the interaction of nanoparticles with the human immune
      system. Further research is required to determine the specific mechanisms for
      reduction of immune activation seen here which could then be used to design a
      truly 'stealth' nanoparticle.

PMID- 24938617
TI  - Aerodynamic and electrostatic properties of model dry powder aerosols: a
      comprehensive study of formulation factors.
AB  - The impact of formulation variables on aerodynamic and electrostatic properties
      of dry powder aerosol particles is of great importance to the development of
      efficient and reproducible inhaler products. Systematic evaluation requires a
      well-designed series of experiments using appropriate methods. A factorial
      experimental design was employed. In broad terms, the conditions considered were
      two drugs, albuterol and budesonide, in combination with different excipients,
      drug concentrations, delivered doses, and metering system (capsule composition)
      and sampled under different flow conditions using standard entrainment tubes.
      Samples were collected in an electrical low-pressure impactor, to evaluate
      distribution of electrostatic properties, and an Andersen eight-stage nonviable
      cascade impactor, to estimate aerodynamic particle size distribution,
      concurrently. The deposition studies allowed calculation of approximate per
      particle charge levels for drug. The results showed very high particle charge
      levels, often in the 1,000-10,000 of elementary charges per particle range,
      orders of magnitude higher than charge levels predicted by the Boltzmann charge
      distribution. The charge levels are considerably higher than had previously been
      estimated (200e per particle).

PMID- 24938618
TI  - Glass delamination: a comparison of the inner surface performance of vials and
      pre-filled syringes.
AB  - The occurrence of glass delamination is a serious concern for parenteral drug
      products. Over the past several years, there has been a series of product recalls
      involving glass delamination in parenteral drugs stored in vials which has led to
      heightened industry and regulatory scrutiny. In this study, a two-pronged
      approach was employed to assess the inner surface durability of vials and pre
      filled syringes. Non-siliconized syringes were used in order to directly compare
      glass to glass performance between vials and syringes. The vial and syringe
      performance was screened with pharmaceutically relevant formulation conditions.
      The influence of pH, buffer type, ionic strength, and glass type and source was
      evaluated. In addition, an aggressive but discriminating formulation condition
      (glutaric acid, pH 11) was used to ascertain the impact of syringe processing.
      Advanced analytical tools including inductively coupled plasma/mass spectrometry,
      scanning electron microscopy, atomic force microscopy, and dynamic secondary ion
      mass spectroscopy showed significant differences in glass performance between
      vials and syringes. Pre-filled syringes outperform vials for most tests and
      conditions. The manufacturing conditions for vials lead to glass defects, not
      found in pre-filled syringes, which result in a less chemically resistant
      surface. The screening methodology presented in this work can be applied to
      assess suitability of primary containers for specific drug applications.

PMID- 24938619
TI  - Constructing all carbon nanotube hollow fiber membranes with improved performance
      in separation and antifouling for water treatment.
AB  - Manipulating carbon nanotubes (CNTs) through engineering into advanced membranes
      with superior performance for disinfection and decontamination of water shows
      great promise but is challenging. In this paper, a facile assembly of CNTs into
      novel hollow fiber membranes with tunable inner/outer diameters and structures is
      developed for the first time. These free-standing membranes composed entirely of
      CNTs feature a porosity of 86+/-5% and a permeation flux of about 460+/-50 L m(
      2) h(-1) at a pressure differential of 0.04 MPa across the membrane. The randomly
      oriented interwoven structure of CNTs endows the membranes considerable
      resistance to pore blockage. Moreover, the adsorption capability of the CNT
      hollow fiber membranes, which is crucial in the efficient removal of small and
      trace contaminant molecules, is about 2 orders of magnitude higher than that of
      commercial polyvinylidene fluoride hollow fiber membranes. The unique advantage
      of the CNT hollow fiber membranes over other commercial membranes is that they
      can be in situ electrochemically regenerated after adsorption saturation.

PMID- 24938620
TI  - Experimental chondrocyte hypertrophy is promoted by the activation of discoidin
      domain receptor 2.
AB  - The aim of the present study was to assess the association between chondrocytes
      and the extracellular matrix (ECM), and determine whether this contributes to
      osteoarthritis (OA). Chondrocyte hypertrophy was measured in articular cartilage
      samples from early-stage OA patients. In addition, rat chondrocytes were cultured
      and divided into four groups (A to D): Group A was an untreated control group,
      group B was incubated with chicken collagen II, group C was transfected with the
      discoidin domain of discoidin domain receptor-2 (DDR2) and group D was
      transfected with full-length DDR2. The expression levels of DDR2 and hypertrophic
      markers in each group were then measured by quantitative polymerase chain
      reaction (qPCR) and western blot analyses. Chondrocyte hypertrophy was identified
      in samples of early-stage OA patients. In rat chondrocyte cultures, the relative
      mRNA and protein expression levels of hypertrophic markers were determined as:
      Group D > B > C > A. In conclusion, transfection with DDR2 induced the expression
      of hypertrophic markers, as assessed by qPCR and western blot analyses. DDR2
      therefore promoted chondrocyte hypertrophy and terminal differentiation.

PMID- 24938621
TI  - An effect of moderate hepatic impairment on the pharmacokinetics and safety of
      darapladib.
AB  - AIM/METHODS: This was a phase 1, open label, non-randomized study designed to
      assess the pharmacokinetics and safety/tolerability of 10 consecutive once daily
      40 mg oral doses of darapladib in subjects with moderate hepatic impairment (n =
      12) compared with matched healthy volunteers (n = 12). RESULTS: For total
      darapladib, a small increase in total and peak exposure was observed in the
      subjects with moderate hepatic impairment compared with the subjects with normal
      hepatic function. The area under the plasma concentration-time curve during a
      dosing interval of duration tau (AUC(0,tau), geometric mean 223 ng ml(-1)  h [90%
      CI 158, 316 ng ml(-1 ) h], in moderate hepatic impaired subjects, vs. geometric
      mean 186 ng ml(-1 ) h [90% CI 159, 217 ng ml(-1 ) h], in healthy subjects) and
      maximum concentration (Cmax ) were 20% and 7% higher, respectively, in the
      subjects with moderate hepatic impairment than in the healthy control subjects
      and there was no change in time to maximum concentration (tmax ). Protein binding
      was performed to measure the amount of unbound drug vs. bound. Steady-state was
      achieved by day 10 for darapladib and its metabolites (M4, M3 and M10).
      Darapladib was generally well tolerated, with adverse events (AEs) reported by
      seven subjects in the hepatic impairment group and three subjects in the healthy
      matched group (five and one of which were drug-related AEs, respectively). The
      most common AEs were gastrointestinal. These AEs were mostly mild to moderate and
      there were no deaths, serious AEs or withdrawals due to AEs. CONCLUSIONS: The
      results of this phase 1 study show that darapladib (40 mg) is well tolerated and
      its pharmacokinetics remain relatively unchanged in patients with moderate
      hepatic impairment.

PMID- 24938623
TI  - Oriented circular dichroism analysis of chiral surface-anchored metal-organic
      frameworks grown by liquid-phase epitaxy and upon loading with chiral guest
      compounds.
AB  - Oriented circular dichroism (OCD) is explored and successfully applied to
      investigate chiral surface-anchored metal-organic frameworks (SURMOFs) based on
      camphoric acid (D- and Lcam) with the composition [Cu2(Dcam)(2x)(Lcam)(2
      2x)(dabco)]n (dabco = 1,4-diazabicyclo-[2.2.2]-octane). The three-dimensional
      chiral SURMOFs with high-quality orientation were grown on quartz glass plates by
      using a layer-by-layer liquid-phase epitaxy method. The growth orientation, as
      determined by X-ray diffraction (XRD), could be switched between the [001] and
      [110] direction by using either OH- or COOH-terminated substrates. These SURMOFs
      were characterized by using OCD, which confirmed the ratio as well as the
      orientation of the enantiomeric linker molecules. Theoretical computations
      demonstrate that the OCD band intensities of the enantiopure [Cu2(Dcam)2(dabco)]n
      grown in different orientations are a direct result of the anisotropic nature of
      the chiral SURMOFs. Finally, the enantiopure [Cu2(Dcam)2(dabco)]n and
      [Cu2(Lcam)2(dabco)]n SURMOFs were loaded with the two chiral forms of ethyl
      lactate [(+)-ethyl-D-lactate and (-)-ethyl-L-lactate)]. An enantioselective
      enrichment of >60 % was observed by OCD when the chiral host scaffold was loaded
      from the racemic mixture.

PMID- 24938622
TI  - Comparison of the effects of beta3 -adrenoceptor agonism on urinary bladder
      function in conscious, anesthetized, and spinal cord injured rats.
AB  - AIMS: To compare the dose effect relationship of a selective beta3 -adrenoceptor
      agonist (CL-316,243) on cystometric parameters in anesthetized and conscious rats
      and to evaluate its effect in a model of neurogenic bladder overactivity induced
      by spinal cord injury (SCI). METHODS: Experiments were performed in anesthetized
      and conscious normal rats and in conscious rats after complete transection at the
      T8 level of the spinal cord. The jugular vein and urinary bladder were
      catheterized and the bladder infused with saline. CL-316,243 was tested
      intravenously at 0.01, 0.03, and 0.1 mg/kg in anesthetized and conscious rats and
      at 0.01 mg/kg in sham and SCI rats. Intravesical pressure was recorded for 1 hr
      following drug administration. Intercontraction interval (ICI), amplitude of
      micturition (AM), micturition frequency (MF) and non-voiding contractions (NVC)
      were analyzed. RESULTS: In anesthetized and conscious normal rats, CL-316,243
      significantly increased ICI in a dose-dependent manner. In anesthetized rats, AM
      was significantly decreased at all doses tested whereas in conscious rats, a
      significant decrease (-19 +/- 6%) in AM was only observed at the highest dose
      (0.1 mg/kg). In conscious sham and SCI rats, CL-316,243 significantly increased
      ICI (42 +/- 17% and 49 +/- 17%, respectively) and decreased MF without affecting
      AM. In SCI rats, CL-316,243 reduced the frequency of NVC (-53 +/- 14%) without
      significant effects on amplitude. CONCLUSIONS: The current results suggest that
      anesthesia can alter the effects of beta3 -adrenoceptor agonists in experimental
      models. In addition, this is the first demonstration that stimulation of beta3 
      adrenoceptors can produce decreases in micturition frequency and NVC in SCI rats
      without affecting AM.

PMID- 24938624
TI  - MicroRNA target prediction: theory and practice.
AB  - The present study is one of the few that includes tissue samples in the
      evaluation of target prediction algorithms designed to detect microRNA (miRNA)
      sequences that might interact with particular messenger RNA (mRNA) sequences.
      Twelve different target prediction tools were used to find miRNA sequences that
      might interact with CCL20 gene expression. Different algorithms predicted
      controversial miRNA sequences for CCL20 regulation due to a different weighting
      of parameters. Hsa-miR-21 and hsa-miR-145 suggested by four or more programs were
      chosen for further investigation. Possible real interaction of these miRNA
      sequences with CCL20 gene expression was monitored using luciferase assays and
      expression analyses of tissue samples of colorectal adenocarcinoma by either qRT
      PCR or ELISA. Folding status of seed-binding sites in complete mRNA and 3'UTR of
      CCL20 was predicted. Prediction of miRNA expression was attempted based on CCL20
      expression data. Eight of the target prediction tools forecasted a role for hsa
      miR-21 and four mentioned hsa-miR-145 in CCL20 gene regulation. Laboratory
      experimentation showed that CCL20 may serve as a target of hsa-miR-21 but not hsa
      miR-145. Expression of the molecules resulted in no clear assertion. Folding of
      seed-binding sites was predicted to be relatively constant for the complete mRNA
      and 3'UTR. Predicting miRNA expression based on target gene expression was
      impossible. This might be attributable to the fact that effects of miRNA activity
      may oscillate between gene product repression and activation. Additional
      systematic studies are needed to address this issue. 

PMID- 24938625
TI  - Pericyte protection by edaravone after tissue plasminogen activator treatment in
      rat cerebral ischemia.
AB  - Pericytes play a pivotal role in contraction, mediating inflammation and
      regulation of blood flow in the brain. In this study, changes of pericytes in the
      neurovascular unit (NVU) were examined in relation to the effects of exogenous
      tissue plasminogen activator (tPA) and a free radical scavenger, edaravone.
      Immunohistochemistry and Western blot analyses showed that the overlap between
      platelet-derived growth factor receptor beta-positive pericytes and N
      acetylglucosamine oligomers (NAGO)-positive endothelial cells increased
      significantly at 4 days after 90 min of transient middle cerebral artery
      occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased
      with tPA but recovered with edaravone 4 days after tMCAO with proliferation.
      Thus, tPA treatment damaged pericytes, resulting in the detachment from
      astrocytes and a decrease in glial cell line-derived neurotrophic factor
      secretion. However, treatment with edaravone greatly improved tPA-induced damage
      to pericytes. The present study demonstrates that exogenous tPA strongly damages
      pericytes and destroys the integrity of the NVU, but edaravone treatment can
      greatly ameliorate such damage after acute cerebral ischemia in rats.

PMID- 24938627
TI  - Symptom severity is associated with cardiovascular outcome in patients with
      permanent atrial fibrillation in the RACE II study.
AB  - AIMS: Symptoms and symptom burden have a central place in diagnosis and
      management of atrial fibrillation (AF). The aim of the present study is to
      investigate whether severity of AF symptoms impacts prognosis in permanent AF.
      METHODS AND RESULTS: We studied the relation between AF symptom severity
      [quantified with the Toronto AF Severity Scale (AFSS)] and cardiovascular outcome
      in patients included in the RACE II study. The primary endpoint was a composite
      of cardiovascular morbidity and mortality. Secondary outcome was cardiovascular
      hospitalizations. Of 614 permanent AF patients in RACE II, AFSS questionnaires
      were available in 558 patients (91%). Mean age was 68 +/- 8 years. One hundred
      and seventy-four patients (31%) reported a low score (score 0-3; lowest tertile),
      190 patients (34%) reported a moderate score (score 4-9; middle tertile), and 194
      (35%) reported a high score (score 10-35; highest tertile). Patients with the
      most severe symptoms were more often women, had higher N-terminal prohormone of
      brain natriuretic peptide concentrations, and had more previous heart failure
      hospitalizations. Median follow-up was 3.0 (interquartile range 2.3-3.0) years.
      The primary endpoint occurred most frequently in the highest tertile of the AFSS
      [16 (9%), 19 (10%), 36 (19%), respectively, P = 0.01], being mainly driven by
      heart failure hospitalizations [4 (2%), 1 (1%), 16 (8%), respectively, P <
      0.001]. After multivariable adjustment, higher AFSS scores were associated with
      the primary endpoint [hazard ratio 1.38 (1.15-1.66), P = 0.001], as well as with
      cardiovascular hospitalizations [hazard ratio 1.33 (1.14-1.54), P < 0.001].
      CONCLUSION: In permanent AF, after multivariable adjustment, symptom severity is
      associated with cardiovascular outcome.

PMID- 24938628
TI  - Abnormal electrocardiographic QRS transition zone and risk of mortality in
      individuals free of cardiovascular disease.
AB  - AIMS: We examined the prognostic significance of abnormal electrocardiographic
      QRS transition zone (clockwise and counterclockwise horizontal rotations) in
      individuals free of cardiovascular disease (CVD). METHODS AND RESULTS: A total of
      5541 adults (age 53 +/- 10.4 years, 54% women, 24% non-Hispanic black, 25%
      Hispanic) without CVD or any major electrocardiogram (ECG) abnormalities from the
      US Third National Health and Nutrition Examination Survey were included in this
      analysis. Clockwise and counterclockwise horizontal rotations were defined from
      standard 12-lead ECG using Minnesota ECG Classification. Mortality and cause of
      death were assessed through 2006. At baseline, 282 participants had clockwise
      rotation and 3500 had counterclockwise rotation. During a median follow of 14.6
      years, 1229 deaths occurred of which 415 were due to CVD. In multivariable
      adjusted Cox proportional hazard analysis and compared with normal rotation,
      clockwise rotation was significantly associated with increased risk of all-cause
      mortality {hazard ratio (HR) [95% confidence interval (CI)]: 1.43 (1.15-1.78); P
      = 0.002} and CVD mortality [HR (95% CI): 1.61 (1.09, 2.37) P = 0.016]. In
      contrast, counterclockwise rotation was associated with significantly lower risk
      of all-cause mortality [HR (95% CI): 0.86 (0.76, 0.97); P = 0.017] and non
      significant association with CVD mortality [HR (95% CI): 1.07 (0.86, 1.33); P =
      0.549]. These results were consistent in subgroup analysis stratified by age,
      sex, and race. CONCLUSION: In a diverse community-based population free of CVD
      and compared with normal rotation, clockwise rotation was associated with
      increased risk of all-cause and CVD mortality while counterclockwise rotation was
      associated with lower risk of all-cause mortality and non-significant association
      with CVD mortality. These findings call for attention to these often neglected
      ECG markers, and probably call for revising the current definition of normal
      rotation.

PMID- 24938626
TI  - Age-related macular degeneration and changes in the extracellular matrix.
AB  - Age-related macular degeneration (AMD) is the leading cause of permanent,
      irreversible, central blindness (scotoma in the central visual field that makes
      reading and writing impossible, stereoscopic vision, recognition of colors and
      details) in patients over the age of 50 years in European and North America
      countries, and an important role is attributed to disorders in the regulation of
      the extracellular matrix (ECM). The main aim of this article is to present the
      crucial processes that occur on the level of Bruch's membrane, with special
      consideration of the metalloproteinase substrates, metalloproteinase, and tissue
      inhibitor of metalloproteinase (TIMP). A comprehensive review of the literature
      was performed through MEDLINE and PubMed searches, covering the years 2005-2012,
      using the following keywords: AMD, extracellular matrix, metalloproteinases,
      tissue inhibitors of metalloproteinases, Bruch's membrane, collagen, elastin. In
      the pathogenesis of AMD, a significant role is played by collagen type I and type
      IV; elastin; fibulin-3, -5, and -6; matrix metalloproteinase (MMP)-2, MMP-9, MMP
      14, and MMP-1; and TIMP-3. Other important mechanisms include: ARMS2 and HTR1
      proteins, the complement system, the urokinase plasminogen activator system, and
      pro-renin receptor activation. Continuous rebuilding of the extracellular matrix
      occurs in both early and advanced AMD, simultaneously with the dysfunction of
      retinal pigment epithelium (RPE) cells and endothelial cells. The pathological
      degradation or accumulation of ECM structural components are caused by impairment
      or hyperactivity of specific MMPs/TIMPs complexes, and is also endangered by the
      influence of other mechanisms connected with both genetic and environmental
      factors.

PMID- 24938630
TI  - Atrial arrhythmias in the young: early onset atrial arrhythmias preceding a
      diagnosis of a primary muscular dystrophy.
AB  - AIMS: The aetiology of atrial arrhythmias in the otherwise healthy and young is
      usually unrecognized. We hypothesized that rare cases of atrial arrhythmias in
      the young may represent the initial manifestation of a muscular dystrophy
      syndrome. METHODS AND RESULTS: We describe the clinical characteristics, disease
      progression, results of electrophysiological study, and genetic findings in four
      patients (age <40 years) presenting with idiopathic atrial arrhythmias who
      subsequently received a diagnosis of a muscular dystrophy syndrome. The mean age
      at presentation with atrial arrhythmias was 29.5 years (range, 21-37 years), and
      the mean delay to diagnosis of muscular dystrophy was 3.6 years (range, 0.5-6
      years). Two patients received a subsequent diagnosis of myotonic dystrophy type 1
      and 2 a diagnosis of Emery-Dreifuss muscular dystrophy. Disease-causing genetic
      defects were identified in all four patients. One patient underwent catheter
      ablation of atrial flutter, experiencing improvement in arrhythmia symptoms. Two
      patients required device therapy, each receiving cardiac resynchronization
      therapy-defibrillator implantation for progressive left ventricular dysfunction.
      CONCLUSION: Early onset atrial arrhythmias may be the first clinical
      manifestation of a muscular dystrophy syndrome. Appropriate clinical assessment
      and surveillance may uncover this primary cause and provide an opportunity for
      timely genetic counselling and family screening.

PMID- 24938629
TI  - Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy:
      characterizing a phenotype.
AB  - AIMS: Risk stratification for sudden death in arrhythmogenic right ventricular
      cardiomyopathy (ARVC) is challenging in clinical practice. We lack
      recommendations for the risk stratification of exclusive left-sided phenotypes.
      The aim of this study was to investigate genotype-phenotype correlations in
      patients carrying a novel DSP c.1339C>T, and to review the literature on the
      clinical expression and the outcomes in patients with DSP truncating mutations.
      METHODS AND RESULTS: Genetic screening of the DSP gene was performed in 47
      consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic
      dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a
      family history of sudden death (n = 23) (aged 40 +/- 19 years, 62% males). Three
      unrelated probands with DCM were found to be carriers of a novel mutation
      (c.1339C>T). Cascade family screening led to the identification of 15 relatives
      who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular
      tachycardia was the first clinical manifestation in six patients and nine
      patients were diagnosed with left ventricular impairment (two had overt severe
      disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed
      left ventricular involvement in nine cases and biventricular disease in three
      patients. Extensive fibrotic patterns in six and non-compaction phenotype in five
      patients were the hallmark in imaging. CONCLUSION: DSP c.1339C>T is associated
      with an aggressive clinical phenotype of left-dominant arrhythmogenic
      cardiomyopathy and left ventricular non-compaction. Truncating mutations in
      desmoplakin are consistently associated with aggressive phenotypes and must be
      considered as a risk factor of sudden death. Since ventricular tachycardia occurs
      even in the absence of severe systolic dysfunction, an implantable cardioverter
      defibrillator should be indicated promptly.

PMID- 24938632
TI  - Epigenetics: the TRPM7 ion channel modifies histones.

PMID- 24938633
TI  - Autonomy, special offers and routines: a Q methodological study of industry
      driven marketing influences on young people's drinking behaviour.
AB  - AIM: To identify shared patterns of views in young people relating to the
      influence of industry-driven alcohol marketing (price, promotion, product and
      place of purchase/consumption) on their reported drinking behaviour. DESIGN: Q
      methodology harnessed qualitative and quantitative data to generate distinct
      clusters of opinions as follows: 39 opinion statements were derived from earlier
      in-depth qualitative interviews with 31 young people; by-person factor analysis
      was carried out on 28 participants' (six previous interviewees and 22 new
      recruits) rank orderings of these statements (most-to-least agreement);
      interpretation of the factor arrays was aided by 10-15-minute debriefing
      interviews held immediately following each Q-sort. SETTING: Northeast England
      PARTICIPANTS: Young people aged 14-17 years purposively recruited from high
      schools, higher education colleges, youth centres and youth offending teams.
      FINDINGS: Centroid factor extraction and varimax rotation of factors generated
      three distinct accounts: factor one ('autonomous, sophisticated consumers')
      illustrated a self-defined sense of individuality and autonomy in alcohol
      choices; factor two ('price-driven consumers') appeared price-led, choosing to
      drink what was most accessible or cheapest; and factor three ('context-focused
      consumers') described drinking practices where products were chosen to serve
      specific functions such as being easy to carry while dancing. CONCLUSIONS:
      Considering young people's views on alcohol marketing, different perspectives can
      be identified. These include perceived imperviousness to maketing, responsiveness
      to price and affordability and responsiveness to marketing focusing on youth
      lifestyles.

PMID- 24938631
TI  - The emergence of proteome-wide technologies: systematic analysis of proteins
      comes of age.
AB  - During the lifetime of a cell proteins can change their localization, alter their
      abundance and undergo modifications, all of which cannot be assayed by tracking
      mRNAs alone. Methods to study proteomes directly are coming of age, thereby
      opening new perspectives on the role of post-translational regulation in
      stabilizing the cellular milieu. Proteomics has undergone a revolution, and novel
      technologies for the systematic analysis of proteins have emerged. These methods
      can expand our ability to acquire information from single proteins to proteomes,
      from static to dynamic measures and from the population level to the level of
      single cells. Such approaches promise that proteomes will soon be studied at a
      similar level of dynamic resolution as has been the norm for transcriptomes. 

PMID- 24938634
TI  - Large-scale dissipative particle dynamics simulations of self-assembled
      amphiphilic systems.
AB  - We present large-scale simulation results on the self-assembly of amphiphilic
      systems in bulk solution and under soft confinement. Self-assembled unilamellar
      and multilamellar vesicles are formed from amphiphilic molecules in bulk
      solution. The system is simulated by placing amphiphilic molecules inside large
      unilamellar vesicles (LUVs) and the dynamic soft confinement-induced self
      assembled vesicles are investigated. Moreover, the self-assembly of sickle
      hemoglobin (HbS) is simulated in a crowded and fluctuating intracellular space
      and our results demonstrate that the HbS self-assembles into polymer fibers
      causing the LUV shape to be distorted. 

PMID- 24938635
TI  - Changes in the profiles of smokers seeking cessation treatment and in its
      effectiveness in Galicia (Spain) 2001-10.
AB  - BACKGROUND: In recent years, the prevalence of daily smokers has decreased in all
      developed countries due to a great variety of factors. Despite this decrease, the
      effectiveness of clinical treatments has decreased and several studies report a
      change in smokers' characteristics. The purpose of the present study is to
      analyze the changes in the characteristics of Spanish smokers who seek smoking
      cessation treatment between 2001 and 2010 and the changes in the effectiveness of
      such treatment. METHODS: The sample was made up of 870 smokers who sought
      psychological treatment for giving up smoking at the Smoking Cessation Unit in
      the Faculty of Psychology of the University of Santiago de Compostela (Spain)
      during the period 2001 to 2010. RESULTS: Smokers in the 2006-2010 group, compared
      to those in the 2001-2005 group, were older, smoked fewer cigarettes per day and
      of a brand with fewer mg/nicotine, had been smoking longer, were less motivated
      to give up smoking, and had more antecedents of depression. Quit rates were
      validated by testing smokers' carbon monoxide (CO) levels.Percentages of
      abstinence were higher in the 2001-2005 group than in the 2006-2010 group (58.7%
      vs. 52.15 at the end of treatment, p = 0.05); 30.8% vs. 24.2% at 6 months follow
      up, p = 0.031; 27.5% vs. 22% at 12 months follow-up, p = 0.059). Although
      abstinence decreased more than 5% in the 2006-2010 group there were no
      differences between the two groups in nicotine dependence. Those participants who
      did not assist to the follow-up were considered smokers at pretreatment level.
      CONCLUSIONS: In Spain there has been a qualitative change in the profile of the
      smokers seeking smoking cessation treatment. Treatment effectiveness has
      decreased, and the variables predicting intervention outcome have changed.

PMID- 24938636
TI  - Autoimmune thyroid disease following alemtuzumab therapy and hematopoietic cell
      transplantation in pediatric patients with sickle cell disease.
AB  - Allogenic hematopoietic cell transplantation (alloHCT) is currently the only
      curative treatment option for patients with sickle cell disease. Alemtuzumab is a
      monoclonal antibody directed against CD52 positive cells used in myeloablative
      conditioning regimens for alloHCT. Its use has been associated with development
      of autoimmune disease in adult patients with rheumatologic conditions. We report
      on three cases of new onset autoimmune thyroid disease after alloHCT treatment
      with alemtuzumab in pediatric patients with sickle cell disease.

PMID- 24938637
TI  - Periprocedural outcomes of prophylactic protamine administration for reversal of
      heparin after cryoballoon ablation of atrial fibrillation.
AB  - PURPOSE: The aim of this study was to investigate the efficacy and the safety of
      prophylactic use of protamine in a series of heparinized patients having
      undergone cryoballoon (CB) ablation for atrial fibrillation (AF). METHODS: From
      October 2013 to January 2014, 54 consecutive patients received protamine after CB
      ablation to neutralize unfractionated heparin (UFH) effects. They were
      prospectively included in this study and compared to a control group of 53
      patients who underwent CB ablation without receiving protamine. RESULTS: A total
      of 54 consecutive patients (33 male, 61%; mean age, 58 +/- 12 years) were
      included. Twenty-one patients (39%) presented with hypertension, 17 (31%) with
      dyslipidemia, and 4 (7%) with diabetes. Five patients (9%) had a previous episode
      of ischemic stroke. Mean protamine dose was 68 +/- 22 mg. No adverse reaction to
      protamine was observed. Among patients having received protamine, one (2%)
      experienced a cardiac tamponade requiring non-surgical drainage. No patient
      having undergone protamine administration experienced vascular complications.
      Conversely, the group of patients not treated with protamine had a significantly
      higher incidence of vascular complications as compared to patients having
      undergone protamine infusion (11 vs 0%, p = 0.01). CONCLUSIONS: Reversing effects
      of UFH by the means of protamine administration appears to be safe after CB
      ablation for AF. It can allow in-laboratory sheath removal with potentially less
      vascular complications and no increase of thromboembolic risk. Larger randomized
      studies are needed in order to confirm our findings.

PMID- 24938638
TI  - Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.
AB  - Photoacoustic imaging is a novel hybrid imaging modality combining the high
      spatial resolution of optical imaging with the high penetration depth of
      ultrasound imaging. Here, for the first time, we evaluate the efficacy of various
      photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as
      photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits
      advantages over fluorescence imaging, which is prone to photobleaching and
      autofluorescence interference. In this work, we examined the photoacoustic
      activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis
      [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene
      blue in phantoms, among which zinc phthalocyanine showed the highest
      photoacoustic activity. Subsequently, we evaluated its tumor localization
      efficiency and biodistribution at multiple time points in a murine model using
      photoacoustic imaging. We observed that the probe localized at the tumor within
      10 minutes post injection, reaching peak accumulation around 1 hour and was
      cleared within 24 hours, thus, demonstrating the potential of photosensitizers as
      photoacoustic imaging contrast agents in vivo. This means that the known
      advantages of photosensitizers such as preferential tumor uptake and PDT efficacy
      can be combined with photoacoustic imaging capabilities to achieve longitudinal
      monitoring of cancer progression and therapy in vivo.

PMID- 24938639
TI  - Thermoregulatory plasticity in free-ranging vervet monkeys, Chlorocebus
      pygerythrus.
AB  - We used implanted miniature data loggers to obtain the first measurements of body
      temperature from a free-ranging anthropoid primate. Vervet monkeys (Chlorocebus
      pygerythrus) living in a highly seasonal, semi-arid environment maintained a
      lower mean 24-h body temperature in winter (34.6 +/- 0.5  degrees C) than in
      summer (36.2 +/- 0.1  degrees C), and demonstrated increased heterothermy (as
      indexed by the 24-h amplitude of their body temperature rhythm) in response to
      proximal environmental stressors. The mean 24-h amplitude of the body temperature
      rhythm in summer (2.5 +/- 0.1  degrees C) was lower than that in winter (3.2 +/-
      0.4  degrees C), with the highest amplitude for an individual monkey (5.6 
      degrees C) recorded in winter. The higher amplitude of the body temperature
      rhythm in winter was a consequence primarily of lower 24-h minimum body
      temperatures during the nocturnal phase, when monkeys were inactive. These low
      minimum body temperatures were associated with low black globe temperature (GLMM,
      beta = 0.046, P < 0.001), short photoperiod (beta = 0.010, P < 0.001) and low
      rainfall over the previous 2 months, which we used as a proxy for food
      availability (beta = 0.001, P < 0.001). Despite the lower average winter minimum
      body temperatures, there was no change in the lower modal body temperature
      between winter and summer. Therefore, unlike the regulated physiological
      adjustments proposed for torpor or hibernation, these minimum winter body
      temperatures did not appear to reflect a regulated reduction in body temperature.
      The thermoregulatory plasticity nevertheless may have fitness benefits for vervet
      monkeys.

PMID- 24938640
TI  - Colourimetric and fluorometric substrates for measurement of pullulanase
      activity.
AB  - Specific and highly sensitive colourimetric and fluorometric substrate mixtures
      have been prepared for the measurement of pullulanase and limit-dextrinase
      activity and assays employing these substrates have been developed. These
      mixtures comprise thermostable alpha- and beta-glucosidases and either 4,6-O
      benzylidene-2-chloro-4-nitrophenyl-beta-maltotriosyl (1-6) alpha-maltotrioside
      (BzCNPG3G3, 1) as a colourimetric substrate or 4,6-O-benzylidene-4
      methylumbelliferyl-beta-maltotriosyl (1-6) alpha-maltotrioside (BzMUG3G3, 2) as a
      fluorometric substrate. Hydrolysis of substrates 1 and 2 by exo-acting enzymes
      such as amyloglucosidase, beta-amylase and alpha-glucosidase is prevented by the
      presence of the 4,6-O-benzylidene group on the non-reducing end D-glucosyl
      residue. The substrates are not hydrolysed by any alpha-amylases studied,
      (including those from Aspergillus niger and porcine pancreas) and are resistant
      to hydrolysis by Pseudomonas sp. isoamylase. On hydrolysis by pullulanase, the 2
      chloro-4-nitrophenyl-beta-maltotrioside (3) or 4-methylumbelliferyl-beta
      maltotrioside (4) liberated is immediately hydrolysed to D-glucose and 2-chloro-4
      nitrophenol or 4-methylumbelliferone. The reaction is terminated by the addition
      of a weak alkaline solution leading to the formation of phenolate ions in
      solution whose concentration can be determined using either spectrophotometric or
      fluorometric analysis. The assay procedure is simple to use, specific, accurate,
      robust and readily adapted to automation.

PMID- 24938641
TI  - Physical activity promotion in Latin American populations: a systematic review on
      issues of internal and external validity.
AB  - The purpose of this review was to determine the degree to which physical activity
      interventions for Latin American populations reported on internal and external
      validity factors using the RE-AIM framework (reach & representativeness,
      effectiveness, adoption, implementation, maintenance). We systematically
      identified English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en
      Salud) language studies published between 2001 and 2012 that tested physical
      activity, exercise, or fitness promotion interventions in Latin American
      populations. Cross-sectional/descriptive studies, conducted in Brazil or Spain,
      published in Portuguese, not including a physical activity/fitness/exercise
      outcome, and with one time point assessment were excluded. We reviewed 192
      abstracts and identified 46 studies that met the eligibility criteria (34 in
      English, 12 in Spanish). A validated 21-item RE-AIM abstraction tool was used to
      determine the quality of reporting across studies (0-7 = low, 8-14 = moderate,
      and 15-21 = high). The number of indicators reported ranged from 3-14 (mean = 8.1
      +/- 2.6), with the majority of studies falling in the moderate quality reporting
      category. English and Spanish language articles did not differ on the number of
      indicators reported (8.1 vs. 8.3, respectively). However, Spanish articles
      reported more across reach indicators (62% vs. 43% of indicators), while English
      articles reported more across effectiveness indicators (69% vs 62%). Across RE
      AIM dimensions, indicators for reach (48%), efficacy/effectiveness (67%), and
      implementation (41%) were reported more often than indicators of adoption (25%)
      and maintenance (10%). Few studies reported on the representativeness of
      participants, staff that delivered interventions, or the settings where
      interventions were adopted. Only 13% of the studies reported on quality of life
      and/or potential negative outcomes, 20% reported on intervention fidelity, and
      11% on cost of implementation. Outcomes measured after six months of
      intervention, information on continued delivery and institutionalization of
      interventions, were also seldom reported. Regardless of language of publication,
      physical activity intervention research for Latin Americans should increase
      attention to and measurement of external validity and cost factors that are
      critical in the decision making process in practice settings and can increase the
      likelihood of translation into community or clinical practice. 

PMID- 24938642
TI  - Flap raising on pulsatile perfused cadaveric tissue: a novel method for surgical
      teaching and exercise.
AB  - Exercising flap raising procedures on cadavers is considered a prerequisite to
      prepare for clinical practise. To improve teaching and create conditions as
      realistic as possible, a perfusion device was developed providing pulsatile flow
      through the vessels of different donor sites. A plastic bag filled with red
      stained tab water was placed into a pump, which was driven by an electric motor.
      The bag was set under rhythmic compression with variable frequency and pressure.
      The pedicles of the radial forearm, anterolateral thigh, rectus abdominis,
      fibular and iliac crest flap were cannulated at the origin from their source
      arteries. Flap raising was performed under pulsatile perfusion in 15 fresh bodies
      and subsequently in 6 Thiel-embalmed cadavers during a flap raising course. We
      regularly observed staining of the skin and skin bleeding in fresh bodies and
      less reliable in embalmed cadavers. All flap pedicles showed pulsatile movements,
      and the radial pulse became palpable. Most perforators of the anterolateral thigh
      and osteocutaneous fibular flap could be identified by their pulse. Bleeding from
      bony tissue and venous return was seldom observed. We conclude that pulsatile
      perfusion of cadaveric tissue creates more realistic conditions for flap raising
      and improves teaching for beginners and advanced surgeons. 

PMID- 24938643
TI  - Clinical characteristics of craniomaxillofacial fibrous dysplasia.
AB  - BACKGROUND: The clinical characteristics of craniomaxillofacial fibrous dysplasia
      (FD) have not been clearly identified. The objective of this meta-analysis is to
      assess the predominance of the monostotic form of FD using an evidence-based
      review. Furthermore, we examined the laterality and sex dominance of FD in
      patients from international study populations. METHODS: We performed a systematic
      search of PubMed, Embase, Cochrane Central Register of Systematic Reviews,
      Cochrane Central Register of Controlled Trials and EBSCO for trials published
      through August 2013. Data extracted from the literature were analysed with Review
      manager 5.0.24. RESULTS: The results of this study showed that unilateral FD
      occurred more frequently than bilateral FD (RR, 12.37; 95% CI, 2.92-61.24; P =
      0.008, N = 263 patients). For unilateral FD, there was no significant difference
      between cases involving the left or right side of the face (RR, 0.98; 95% CI,
      0.66-1.44; P = 0.91; N = 201 patients). There were no significant sex-dependent
      differences for monostotic and polyostotic forms of craniomaxillofacial FD.
      CONCLUSION: There is a significantly higher percentage of the unilateral form
      than the bilateral form in the craniomaxillofacial FD studies analysed, and an
      almost equal distribution of left- and right-sided unilateral FD. These
      proportions were maintained among males and females and there were nearly equal
      frequencies of monostotic and polyostotic FD.

PMID- 24938644
TI  - 2-(Hetero(aryl)methylene)hydrazine-1-carbothioamides as potent urease inhibitors.
AB  - A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including
      two aryl derivatives was synthesized and tested for their inhibitory activity
      against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide
      (3f), having a furan ring, was the most potent inhibitor of urease with an IC50
      value of 0.58 MUM. Molecular modeling was carried out through docking the
      designed compounds into the urease binding site to predict whether these
      derivatives have analogous binding mode to the urease inhibitors. The study
      revealed that all of the tested compounds bind with both metal atoms at the
      active site of the enzyme. The aromatic ring of the compounds forms ionic
      interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).

PMID- 24938645
TI  - Bronsted acid catalyzed, conjugate addition of beta-dicarbonyls to in situ
      generated ortho-quinone methides--enantioselective synthesis of 4-aryl-4H
      chromenes.
AB  - We describe herein a catalytic, enantioselective process for the synthesis of 4H
      chromenes which are important structural elements of many natural products and
      biologically active compounds. A sequence comprising a conjugate addition of beta
      diketones to in situ generated ortho-quinone methides followed by a
      cyclodehydration reaction furnished 4-aryl-4H-chromenes in generally excellent
      yields and high optical purity. A BINOL-based chiral phosphoric acid was employed
      as a Bronsted acid catalyst which converted ortho-hydroxy benzhydryl alcohols
      into hydrogen-bonded ortho-quinone methides and effected the carbon-carbon bond
      forming event with high enantioselectivity. 

PMID- 24938646
TI  - Anti-inflammatory effects of Panax notoginseng saponins ameliorate acute lung
      injury induced by oleic acid and lipopolysaccharide in rats.
AB  - This study investigated the effect of Panax notoginseng saponins (PNS) on acute
      lung injury (ALI) induced by oleic acid (OA) and lipopolysaccharide (LPS). A
      total of 28 Wistar rats were divided into four groups: sham; sham + PNS; OA-LPS
      induced ALI and ALI + PNS. Lung tissue histology, lung wet-to-dry (W/D) weight
      ratio, extravascular lung water (EVLW) and epithelial sodium channel alpha
      (alphaENaC) mRNA and protein expression were examined. In addition, levels of
      inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha),
      interleukin (IL)-6 and IL-10, as well as total leukocyte and neutrophil counts,
      were analyzed in rat bronchoalveolar lavage fluid (BALF) and serum. ALI + PNS
      rats were observed to exhibit significantly lower pulmonary parenchymal damage
      and EVLW compared with ALI rats. Furthermore, total leukocyte and neutrophil
      counts, and levels of inflammatory cytokines were significantly decreased
      following PNS administration in ALI rats. In addition, the decrease in alphaENaC
      mRNA and protein expression observed in the lung tissue of ALI rats was partially
      restored following PNS treatment. PNS treatment was demonstrated to ameliorate OA
      LPS-induced ALI, potentially through restoration of alphaENaC mRNA and protein
      expression and through PNS-induced anti-inflammatory effects.

PMID- 24938647
TI  - Microarray of surface-exposed proteins of Rickettsia heilongjiangensis for
      serodiagnosis of Far-eastern spotted fever.
AB  - BACKGROUND: Far-eastern spotted fever (FESF) is an important emerging infectious
      disease in Northeast Asia. The laboratory diagnosis of FESF in hospitals is
      mainly based on serological methods. However, these methods need to cultivate
      rickettsial cells as diagnostic antigens, which is both burdensome and dangerous.
      METHODS: Eleven surface-exposed proteins (SEPs) were identified in our previous
      study and their recombinant proteins (rSEPs) fabricated on a microarray were
      serologically analyzed with seventeen paired sera from patients suffered from
      FESF in this study. RESULTS: All the rSEPs showed sensitivities of between 53%
      and 82% to acute-phase sera and of between 65% and 82% to convalescent-phase
      sera, and all the rSEPs except rRplA showed specificities of between 80% and 95%.
      The combination assay of two, three, or four of the four rSEPs (rOmpA-2, rOmpB-3,
      rRpsB, and rSdhB) showed better sensitivities of between 76% and 94% to the acute
      phase sera or between 82% and 100% to the convalescent-phase sera and acceptable
      specificities of between 75% and 90%. CONCLUSIONS: Our results suggest that the
      four rSEPs are more likely candidate antigens for serological diagnosis of FESF.

PMID- 24938648
TI  - Next generation treatment of acute graft-versus-host disease.
AB  - Despite rapid increase in the utilization of allogeneic hematopoietic stem cell
      transplantation, non-relapse mortality and sequela from acute graft-versus-host
      disease (GVHD) remain principle barriers. GVHD involves complex interactions
      between innate and adaptive immunity, culminating in tissue damage by
      inflammatory mediators and cellular effectors. Recently, our understanding of the
      molecular intricacies of GVHD has grown tremendously. New insights into the roles
      played by novel cytokines, chemokines, intracellular signaling pathways,
      epigenetics and post-translational modifications of proteins in GVHD biology
      provide numerous targets that might be therapeutically exploited. This review
      highlights recent advances and identifies opportunities for reshaping
      contemporary GVHD therapeutics. 

PMID- 24938649
TI  - Sequential myeloablative autologous stem cell transplantation and reduced
      intensity allogeneic hematopoietic cell transplantation is safe and feasible in
      children, adolescents and young adults with poor-risk refractory or recurrent
      Hodgkin and non-Hodgkin lymphoma.
AB  - The outcome of children, adolescents and young adults (CAYA) with poor-risk
      recurrent/refractory lymphoma is dismal (?30%). To overcome this poor prognosis,
      we designed an approach to maximize an allogeneic graft vs lymphoma effect in the
      setting of low disease burden. We conducted a multi-center prospective study of
      myeloablative conditioning (MAC) and autologous stem cell transplantation
      (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic
      hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory
      or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of
      carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine.
      Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with
      a median age of 16 years and median follow-up of 5years, were enrolled. Twenty
      three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor
      sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched
      siblings (n=6). The incidence of transplant-related mortality following RIC
      AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70%
      (P=0.613), respectively. In summary, this approach is safe, and long-term EFS
      with this approach is encouraging considering the poor-risk patient
      characteristics and the use of unrelated donors for RIC AlloHCT in the majority
      of cases. 

PMID- 24938650
TI  - Considerations in establishing a post-mortem brain and tissue bank for the study
      of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol.
AB  - BACKGROUND: Our aim, having previously investigated through a qualitative study
      involving extensive discussions with experts and patients the issues involved in
      establishing and maintaining a disease specific brain and tissue bank for myalgic
      encephalomyelitis/chronic fatigue syndrome (ME/CFS), was to develop a protocol
      for a UK ME/CFS repository of high quality human tissue from well characterised
      subjects with ME/CFS and controls suitable for a broad range of research
      applications. This would involve a specific donor program coupled with rapid
      tissue collection and processing, supplemented by comprehensive prospectively
      collected clinical, laboratory and self-assessment data from cases and controls.
      FINDINGS: We reviewed the operations of existing tissue banks from published
      literature and from their internal protocols and standard operating procedures
      (SOPs). On this basis, we developed the protocol presented here, which was
      designed to meet high technical and ethical standards and legal requirements and
      was based on recommendations of the MRC UK Brain Banks Network. The facility
      would be most efficient and cost-effective if incorporated into an existing
      tissue bank. Tissue collection would be rapid and follow robust protocols to
      ensure preservation sufficient for a wide range of research uses. A central
      tissue bank would have resources both for wide-scale donor recruitment and rapid
      response to donor death for prompt harvesting and processing of tissue.
      CONCLUSION: An ME/CFS brain and tissue bank could be established using this
      protocol. Success would depend on careful consideration of logistic, technical,
      legal and ethical issues, continuous consultation with patients and the donor
      population, and a sustainable model of funding ideally involving research
      councils, health services, and patient charities. This initiative could
      revolutionise the understanding of this still poorly-understood disease and
      enhance development of diagnostic biomarkers and treatments.

PMID- 24938651
TI  - Effectiveness of complex interventions focused on quality-of-life assessment to
      improve palliative care patients' outcomes: a systematic review.
AB  - BACKGROUND: One of the most crucial palliative care challenges is in determining
      how patient' needs are defined and assessed. Assessing quality of life has been
      defined as a priority in palliative care, and it has become a central concept in
      palliative care practice. AIM: To determine to what extent interventions focused
      on measuring quality of life in palliative care practice are effective in
      improving outcomes in palliative care patients. DESIGN: Systematic review
      according to the recommendations of the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) statement and hand searches. DATA SOURCES:
      MEDLINE, CINAHL, EMBASE, PsycINFO, and the Cochrane Library were searched for
      articles published until June 2012, and through hand searching from references
      lists of included articles. Only studies that included adult palliative care
      patients, in any palliative care clinical practice setting of care, and with an
      experimental, quasi-experimental, or observational analytical study design were
      eligible for inclusion. All studies were independently reviewed by two
      investigators who scored them for methodological quality by using the Edwards
      Method Score. RESULTS: In total, 11 articles (of 8579) incorporating information
      from 10 studies were included. Only three were randomized controlled trials. The
      quality of the evidence was found from moderate to low. Given a wide variability
      among patients' outcomes, individual effect size (ES) was possible for 6 out of
      10 studies, 3 of which found a moderate ES on symptoms (ES = 0.68) and
      psychological (ES = 0.60) and social (ES = 0.55) dimensions. CONCLUSION:
      Effectiveness of interventions focused on quality-of-life assessment is moderate.
      Additional studies should explore the complexity of the real palliative care
      world more accurately and understand the effects of independent variables
      included in complex palliative care interventions.

PMID- 24938652
TI  - Uropygial gland size and composition varies according to experimentally modified
      microbiome in Great tits.
AB  - BACKGROUND: Parasites exert important selective pressures on host life history
      traits. In birds, feathers are inhabited by numerous microorganisms, some of them
      being able to degrade feathers or lead to infections. Preening feathers with
      secretions of the uropygial gland has been found to act as an antimicrobial
      defence mechanism, expected to regulate feather microbial communities and thus
      limit feather abrasion and infections. Here, we used an experimental approach to
      test whether Great tits (Parus major) modify their investment in the uropygial
      gland in response to differences in environmental microorganisms. RESULTS: We
      found that males, but not females, modified the size of their gland when exposed
      to higher bacterial densities on feathers. We also identified 16 wax esters in
      the uropygial gland secretions. The relative abundance of some of these esters
      changed in males and females, while the relative abundance of others changed only
      in females when exposed to greater bacterial loads on feathers. CONCLUSION: Birds
      live in a bacterial world composed of commensal and pathogenic microorganisms.
      This study provides the first experimental evidence for modifications of
      investment in the defensive trait that is the uropygial gland in response to
      environmental microorganisms in a wild bird.

PMID- 24938653
TI  - Antibiotic-loaded chitosan hydrogel with superior dual functions: antibacterial
      efficacy and osteoblastic cell responses.
AB  - It is critical for the clinical success to take the biological function into
      consideration when integrating the antibacterial function into the implanted
      biomaterials. To this aim, we prepared gentamycin sulfate (GS)-loaded
      carboxymethyl-chitosan (CM-chitosan) hydrogel cross-linked by genipin. The
      prepared hydrogels not only achieved superb inhibition on bacteria growth and
      biofilm formation of Staphylococcus aureus but also significantly enhanced the
      adhesion, proliferation, and differentiation of MC3T3-E1 cells. The observed dual
      functions were likely based on the intrinsic property of the positive charged
      chitosan-based hydrogel, which could be modified to selectively disrupt the
      bacteria wall/membrane and promote cell adhesion and proliferation, as suggested
      by the membrane permeability study. The genipin concentration played an important
      role in controlling the degradation time of the chitosan hydrogel and the MC3T3
      E1 cell responses. The loading of GS not only significantly increased the
      antibacterial efficiency but also was beneficial for the osteoblastic cell
      responses. Overall, the biocompatibility of the prepared chitosan-GS hydrogel
      could be tuned with both the genipin and GS concentrations, which control the
      available positive charged sites of chitosan. The results demonstrated that
      chitosan-GS hydrogel is an effective and simple approach to achieving combined
      antibacterial efficacy and excellent osteoblastic cell responses, which has great
      potential in orthopedic applications. 

PMID- 24938654
TI  - Focal abnormalities in idiopathic generalized epilepsy: a critical review of the
      literature.
AB  - Conventionally, epilepsy is dichotomized into distinct "focal" and "generalized"
      categories. However, many studies have reported so-called focal features among
      patients with idiopathic generalized epilepsy (IGE) in the domains of semiology,
      electroencephalography, neuropsychology, neuropathology, and neuroimaging. We
      sought to review such features and clinical implications. A Web of Science
      database search was conducted to identify relevant publications. Our search
      yielded 145 papers describing focal features involving different domains in IGE,
      with 117 papers analyzed after excluding abstracts and case reports. Focal
      semiologic features are commonly seen in IGE. There are conflicting data from
      studies in the domains of electroencephalography, neuroimaging, and
      neuropathology. Studies on neuropsychology are suggestive of frontal lobe
      functional deficits in juvenile myoclonic epilepsy. Most advanced neuroimaging
      studies demonstrate the involvement of both the thalamus and the cortex during
      generalized spike-wave discharges (GSWDs). A few electroencephalographic and
      neuroimaging studies indicate that the cortex precedes the thalamus at the onset
      of GSWD. Focal features may contribute to misdiagnosis of IGE as focal epilepsy.
      However there are methodologic limitations in the studies that affect the
      results.

PMID- 24938655
TI  - Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV
      antiretroviral treatment.
AB  - BACKGROUND: Compensatory mutations have been observed to emerge with drug
      resistance (DR) mutations, but their effects on virological response to treatment
      have not been fully examined. In this study, we characterized the emergence and
      depletion dynamics of a compensatory mutation K43E that correlated with primary
      nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations in
      Chinese HIV patients on antiretroviral treatment. METHOD: Single Genome
      Amplification (SGA) was used to obtain the HIV-1 pol gene quasispecies in three
      patients over 6 years of Antiretroviral Therapy (ART) treatment. SGA sequences
      were analyzed by Markov Chain Monte Carlo (MCMC) phylogenetic trees with
      molecular clock to identify and track compensatory mutation K43E correlated with
      primary DR mutation M41L. We evaluated the relationship between potential
      compensatory mutation and DR mutations through Ka/Ks ratio, Jaccard similarity
      coefficient, and compared these with concurrent viral load data. CONCLUSION: We
      determined that a known compensatory mutation, K43E, frequently co-occurs with
      the drug resistance mutation M41L and may offer a significant advantage in the
      long-term survival of such drug resistant strains.

PMID- 24938656
TI  - Petawatt laser absorption bounded.
AB  - The interaction of petawatt (10(15) W) lasers with solid matter forms the basis
      for advanced scientific applications such as table-top particle accelerators,
      ultrafast imaging systems and laser fusion. Key metrics for these applications
      relate to absorption, yet conditions in this regime are so nonlinear that it is
      often impossible to know the fraction of absorbed light f, and even the range of
      f is unknown. Here using a relativistic Rankine-Hugoniot-like analysis, we show
      for the first time that f exhibits a theoretical maximum and minimum. These
      bounds constrain nonlinear absorption mechanisms across the petawatt regime,
      forbidding high absorption values at low laser power and low absorption values at
      high laser power. For applications needing to circumvent the absorption bounds,
      these results will accelerate a shift from solid targets, towards structured and
      multilayer targets, and lead the development of new materials. 

PMID- 24938658
TI  - Individually adapted tube current selection and contrast medium injection
      protocol of coronary CT angiography based on test bolus parameters: a feasibility
      study.
AB  - BACKGROUND: Test bolus is mostly used to determine the starting point of a full
      cardiac scanning with respect to injection of a larger bolus of contrast
      material. So far there are limited data demonstrating the feasibility of using
      information obtained from a test bolus to adjust contrast delivery protocols and
      tube current individually during coronary computed tomography angiography (CCTA).
      PURPOSE: To evaluate the feasibility of individually adapted tube current
      selection and contrast injection protocols of CCTA based on test bolus
      parameters. MATERIAL AND METHODS: Test bolus followed by CCTA was performed in 93
      patients at 100 kV and in 81 patients at 120 kV, respectively. Simulated
      attenuation of the descending aorta (SimDA) of CCTA was calculated at a fixed
      contrast injection rate of 4 mL/s. Univariate and multivariate comparisons were
      performed to identify associations of SimDA and image noise of CCTA (NoiseCCTA)
      with test bolus information and patient-related factors including body weight
      (BW), body mass index (BMI), and body surface area (BSA). RESULTS: Compared with
      BW, BMI, and BSA, SimDA was more closely related to the peak time of left
      ventricle and peak enhancement of right ventricle obtained from test bolus (r =
      0.495 and r = 0.642 for 100 and 120 kV protocol, respectively). Similarly,
      NoiseTB was much more closely related to NoiseCCTA (r = 0.740 and r = 0.630 for
      100 and 120 kV protocol, respectively) when compared with BW, BMI, and BSA.
      CONCLUSION: It is feasible to individually adapt tube current and contrast
      injection protocol of CCTA based on the information of test bolus.

PMID- 24938657
TI  - Comparative analysis of conjugated alkynyl chromophore-triazacyclononane ligands
      for sensitized emission of europium and terbium.
AB  - A series of europium and terbium complexes based on a functionalized
      triazacyclononane carboxylate or phosphinate macrocyclic ligand is described. The
      influence of the anionic group, that is, carboxylate, methylphosphinate, or
      phenylphosphinate, on the photophysical properties was studied and rationalized
      on the basis of DFT calculated structures. The nature, number, and position of
      electron-donating or electron-withdrawing aryl substituents were varied
      systematically within the same phenylethynyl scaffold in order to optimize the
      brightness of the corresponding europium complexes and investigate their two
      photon absorption properties. Finally, the europium complexes were examined in
      cell-imaging applications, and selected terbium complexes were studied as
      potential oxygen sensors. 

PMID- 24938659
TI  - A focal marked hypoechogenicity within an isoechoic thyroid nodule: is it a focal
      malignancy or not?
AB  - BACKGROUND: A marked hypoechogenicity is a reliable criterion for a malignant
      nodule, whereas isoechogenicity is considered to be a benign ultrasonographic
      (US) finding. However, there have been no reports to demonstrate whether a focal
      marked hypoechogenicity within an isoechoic nodule is a focal malignancy.
      PURPOSE: To evaluate whether a focal marked hypoechogenicity within an isoechoic
      nodule on US examination is a focal malignancy and to correlate US histologic
      findings using surgical or core needle biopsy (CNB) specimens. MATERIAL AND
      METHODS: From January 2010 to August 2011, 28 consecutive patients (25 women, 3
      men; mean age, 52.2 years) with 29 thyroid nodules, which showed a focal marked
      hypoechogenicity within an isoechoic nodule on US, underwent US-guided CNB for a
      suspicion of a focal malignancy. All nodules were confirmed by surgery (n = 6) or
      more than two consecutive US-guided biopsies (n = 23). We evaluated the risk of
      malignancy, and analyzed histological components which correlated with a focal
      marked hypoechogenic area within an isoechoic nodule on US. Statistical analysis
      was performed using the Mann-Whitney U test and Fisher's exact test. RESULTS: Of
      the 29 nodules, 25 were benign (86.2%) and four were malignant (13.8%). The
      peripheral location of focal marked hypoechogenicity within an isoechoic nodule
      was the only significant US finding that suggested malignancy (P = 0.03). All
      benign focal marked hypoechogenicities were histologically composed of severe
      fibrosis with a few follicular cells with varying frequencies of hemosiderin,
      calcification, infarction, and granulation tissue. CONCLUSION: Although a focal
      marked hypoechogenicity within an isoechoic nodule is usually benign, the
      peripheral location of a focal marked hypoechogenicity may be a malignancy. The
      histologic information obtained by CNB specimen may reduce the needs for
      repetitive fine needle aspirations or diagnostic surgery.

PMID- 24938660
TI  - Invasive cribriform carcinoma of the breast: mammographic, sonographic, MRI, and
      18 F-FDG PET-CT features.
AB  - BACKGROUND: Invasive cribriform carcinoma (ICC) of the breast is a rare type of
      invasive carcinoma which shows a favorable prognosis and a lower frequency of
      axillary nodal metastases. Few imaging findings related to ICC have been
      reported. PURPOSE: To evaluate imaging findings with multiple imaging techniques
      in ICC of the breast. MATERIAL AND METHODS: Twenty-eight cases of
      histopathologically proven ICC of the breast were gathered for this study. We
      retrospectively reviewed the mammographic, sonographic, and magnetic resonance
      imaging (MRI) findings of ICC according to the American College of Radiology
      (ACR) breast imaging reporting and data system (BI-RADS) lexicon. 18 F
      fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET
      CT) findings were also evaluated. Microscopic slides of surgical specimens were
      reviewed by a breast pathologist. RESULTS: The mean age of the patients was 51
      years. The most common mammographic findings were irregular shape (72.8%),
      spiculated margin (63.7%), and a high density (81.8%) mass. Microcalcifications
      were noted in 9/28 cases. The most common shape was pleomorphic (66.7%). The most
      common sonographic findings were irregular shape (77.8%), spiculated margin
      (29.6%), hypoechogenicity (81.5%), and no posterior acoustic features (85.2%). On
      MRI, most ICCs presented as irregular shaped mass (62.0%) and irregular (42.9%)
      margin. All four patients (16.0%) who presented with non-mass-like enhancement
      pattern showed a segmental distribution. The 18 F-FDG PET-CT showed a mean
      maximum standardized uptake value (SUVmax) of 5.90. Axillary nodal metastases
      were found in 17.9% (5/28) of the surgical specimens. Immunohistochemical studies
      showed a high positivity for estrogen and progesterone receptor (100% and 87.5%,
      respectively). CONCLUSION: The imaging features of invasive cribriform carcinoma
      are highly suggestive of malignancy and are not distinguishable from those of
      other breast cancers like infiltrating ductal carcinoma.

PMID- 24938662
TI  - Safety in simultaneous EEG-fMRI at 3 T: temperature measurements.
AB  - BACKGROUND: In simultaneous electroencephalography (EEG) and functional magnetic
      resonance imaging (fMRI), safety of the EEG equipment is ensured by the
      manufacturer only for localizers and fMRI sequences. To conduct a clinically
      feasible simultaneous EEG-fMRI study, other sequences, e.g. anatomical and B0
      correction sequences, have to be acquired in the same imaging session. PURPOSE:
      To measure the temperature increase of the electrodes in different size EEG caps
      in a phantom and volunteers during magnetic resonance imaging (MRI) sequences
      typically used in clinical studies. MATERIAL AND METHODS: A phantom with EEG caps
      of size 52, 56, and 60 was imaged using several sequences in two 3 T MRI scanners
      to determine the maximum and average temperature increases in the electrodes.
      Additionally, three volunteer studies were performed for the EEG caps of sizes 56
      and 60. The sequences were gradient echo based echo planar imaging sequence, T2
      weighted turbo spin echo (T2-TSE), spin echo multiecho for B0-correction,
      diffusion tensor imaging and T1-weighted 3D sequences. RESULTS: In phantom
      studies the maximum temperature increase was 4.1C with a mean of 1.2 +/- 1.1C. In
      volunteer studies, the maximum temperature measured was 35.6C and the maximum
      temperature rise was 2.1C with a mean of 0.9 +/- 0.7C. Both were observed with a
      T2-TSE sequence. CONCLUSION: The temperature of the electrodes did not exceed the
      limits set by the IEC 60601-1 standard (43C) or manufacturer (45C), thus
      indicating a safe EEG-fMRI protocol in this respect.

PMID- 24938661
TI  - Intra-arterial and intravenous applications of Iosimenol 340 injection, a new non
      ionic, dimeric, iso-osmolar radiographic contrast medium: phase 2 experience.
AB  - BACKGROUND: Iosimenol 340 injection is a new, dimeric, iso-osmolar, iodinated
      contrast medium for X-ray angiography. PURPOSE: To compare the safety and
      efficacy of iosimenol injection to iodixanol injection in two randomized,
      controlled phase 2 trials. MATERIAL AND METHODS: One hundred and forty-four adult
      patients were enrolled in the two trials, one for evaluation during arteriography
      and the other for evaluation during computed tomography. Safety was compared by
      assessing adverse events, vital signs, ECGs, and laboratory parameters. Efficacy
      was assessed as X-ray attenuation in the computed tomography (CT) trial and as
      the quality of contrast enhancement in the arteriography trial. RESULTS: There
      were no statistically significant differences in terms of safety or efficacy
      between the two contrast media. Both were well tolerated upon intravenous as well
      as intra-arterial injection. The most common adverse event was a feeling of
      warmth (observed in 35.1% of the patients with Iosimenol injection and 44.3% with
      iodixanol injection). CONCLUSION: Iosimenol upon intravenous as well as upon
      intra-arterial injection exhibits a safety profile and shows an efficacy similar
      to that of iodixanol.

PMID- 24938663
TI  - Diagnostic performance of indirect MR arthrography for the diagnosis of rotator
      cuff tears at 3.0 T.
AB  - BACKGROUND: Indirect magnetic resonance (MR) arthrography is a non-invasive
      method for shoulder imaging. However, there are no studies that have examined the
      diagnostic performance of indirect MR arthrography for the diagnosis of rotator
      cuff tears in a large patient population. PURPOSE: To assess the diagnostic
      performance of indirect fast spin-echo (FSE) MR arthrography for the diagnosis of
      rotator cuff tears at 3.0 T. MATERIAL AND METHODS: A total of 149 patients who
      had undergone indirect shoulder MR arthrography followed by arthroscopic surgery
      were enrolled in this retrospective study. Two musculoskeletal radiologists
      evaluated images from each patient for the presence of supraspinatus
      infraspinatus (SSP-ISP) or subscapularis (SSC) tendon tears. Using the
      arthroscopic findings as the reference standard, the overall diagnostic
      performance and detection rates for SSP-ISP and SSC tendon tears were calculated.
      RESULTS: The sensitivity, specificity, and accuracy of readers I and II for the
      diagnosis of SSP-ISP tendon tears were 94% and 95%, 89% and 85%, and 93% and 93%,
      respectively. The sensitivity of imaging for detection of SSP-ISP tendon tears by
      readers I and II were 100% and 100% for full-thickness tears and 84% and 86% for
      partial-thickness tears, respectively. The sensitivity, specificity, and accuracy
      of readers I and II for the diagnosis of SSC tendon tears were 80% and 76%, 89%
      and 93%, and 85% and 85%, respectively. CONCLUSION: Indirect MR arthrography is
      useful for the detection of SSP-ISP and SSC tendon tears.

PMID- 24938664
TI  - In vivo characterization of urinary calculi on dual-energy CT: going a step ahead
      with sub-differentiation of calcium stones.
AB  - BACKGROUND: The role of dual-energy computed tomography (DECT) in
      characterization of urinary calculi is evolving and literature regarding
      differentiation of calcium calculi is sparse and confounding. PURPOSE: To
      evaluate the capability of DECT in assessing the urinary calculi composition in
      vivo, especially in differentiating various types of calcium calculi. MATERIAL
      AND METHODS: One hundred and twenty patients underwent DECT for characterization
      of urinary calculi. Seventy patients with 114 calculi, including 93 calcium
      stones, were retrospectively analyzed. DE ratios and attenuation differences were
      compared using ANOVA and receiver-operating-characteristic (ROC) analysis was
      done to predict cut-off values, in particular for detecting calcium-oxalate
      monohydrate (COM) stones. RESULTS: DE ratio <=1.14 accurately detected uric acid
      calculi, >=1.29 was definitive for calcium and intermediate values were
      characteristic of cystine stones. DE ratios were significantly different between
      group 1 (COM [n = 32]; mean 1.376 +/- 0.041), group 2 ([calcium oxalate dihydrate
      (COD) + COM] [n = 51]; 1.416 +/- 0.048), and group 3 ([carbonate apatite (CaP) +
      COD + COM] [n = 10]; 1.468 +/- 0.038) (group 1 vs. 2, P = 0.001; 1 vs. 3, P =
      0.000; 2 vs. 3, P = 0.004). More importantly, pure COM calculi (group 1) had
      significantly lower DE ratio compared with mixed calcium calculi (groups 2 and 3)
      (P = 0.000). Attenuation differences (between low and high kV images) could not
      distinguish between COM and mixed calculi. ROC analysis for detection of COM
      calculi yielded AUC of 0.770 with cut-off DE ratio 1.385 (sensitivity 65.6%,
      specificity 82%) and value <1.335 was seen only with COM calculi (100%
      specificity). CONCLUSION: DECT can be employed for in vivo differentiation of
      various types of calculi and for detection of relatively lithotripsy-resistant
      COM calculi.

PMID- 24938665
TI  - Myosin IIb controls actin dynamics underlying the dendritic spine maturation.
AB  - Precise control of the formation and development of dendritic spines is critical
      for synaptic plasticity. Consequently, abnormal spine development is linked to
      various neurological disorders. The actin cytoskeleton is a structural element
      generating specific changes in dendritic spine morphology. Although mechanisms
      underlying dendritic filopodia elongation and spine head growth are relatively
      well understood, it is still not known how spine heads are enlarged and
      stabilized during dendritic spine maturation. By using rat hippocampal neurons,
      we demonstrate that the size of the stable actin pool increases during the
      neuronal maturation process. Simultaneously, the treadmilling rate of the dynamic
      actin pool increases. We further show that myosin IIb controls dendritic spine
      actin cytoskeleton by regulating these two different pools of F-actin via
      distinct mechanisms. The findings indicate that myosin IIb stabilizes the stable
      F-actin pool through actin cross-linking. Simultaneously, activation of myosin
      IIb contractility increases the treadmilling rate of the dynamic pool of actin.
      Collectively, these data show that myosin IIb has a major role in the regulation
      of actin filament stability in dendritic spines, and elucidate the complex
      mechanism through which myosin IIb functions in this process. These new insights
      into the mechanisms underlying dendritic spine maturation further the model of
      dendritic spine morphogenesis.

PMID- 24938666
TI  - Compounds from marine-derived Verrucosispora sp. FIM06054 and their potential
      antitumour activities.
AB  - Strain FIM06054 was isolated from a marine sponge sample collected from the East
      China Sea and was characterised as a strain of Verrucosispora genus on the basis
      of its 16S rRNA gene sequence. One new compound, FW054-1 (1), together with a
      known aminofuran compound proximicin A (2), was isolated from the culture broth
      of Verrucosispora sp. FIM06054. Their structures were elucidated on the basis of
      spectral analysis. 1 and 2 showed antiproliferative activity against several
      human tumour cell lines. 

PMID- 24938668
TI  - What every radiologist should know about paediatric echocardiography.
AB  - Congenital heart defects (CHD) occur in less than one percent of all newborns.
      Echocardiography represents the imaging modality of choice for morphological and
      functional assessment. In childhood the different CHD types can be diagnosed
      trustfully and can be performed bedside. In the follow-up of CHD cross sectional
      imaging plays an important role and therefore it is essential for the radiologist
      to know the features, challenges and limitations of echocardiography. Within this
      review article a systematic approach for morphological and functional assessment
      of the heart will is given along with representative example images. In addition,
      typical echocardiographic findings in common CHD is presented. In older children,
      adolescents and grown-ups with CHD (GUCH) echocardiography suffers from
      limitations - partially due to skeletal deformations and lung emphysema. In
      particular right ventricular function assessment is not always possible by
      echocardiography. Therefore strengths and limitations of echocardiography will be
      discussed the role of cardiac magnetic resonance imaging (cMRI) and cardiac
      computed tomography (cCT) emphasized. 

PMID- 24938667
TI  - Characteristics, survival, and related factors of newly diagnosed colorectal
      cancer patients refusing cancer treatments under a universal health insurance
      program.
AB  - BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer
      worldwide. Few studies have addressed the causes and risks of treatment refusal
      in a universal health insurance setting. METHODS: We examined the characteristics
      and survival associated with treatment refusal in patients with newly diagnosed
      colorectal cancer in Taiwan during 2004-2008. Treatment refusal was defined as
      not undergoing any cancer treatment within 4 months of confirmed cancer
      diagnosis. Patient data were extracted from four national databases. Factors
      associated with treatment refusal were identified through logistic regression
      using the generalized estimating equation method, and survival analysis was
      performed using the Cox proportional hazards model. RESULTS: Of the 41,340 new
      colorectal cancer cases diagnosed, 3,612 patients (8.74%) refused treatment.
      Treatment refusal rate was higher in patients with less urbanized areas of
      residence, lower incomes, preexisting catastrophic illnesses, cancer stages of 0
      and IV, and diagnoses at regional and district hospitals. Logistic regression
      analysis revealed that patients aged >75 years were the most likely to refuse
      treatment (OR, 1.87); patients with catastrophic illnesses (OR, 1.66) and stage
      IV cancer (OR, 1.43) had significantly higher refusal rates. The treatment
      refusers had 2.66 times the risk of death of those who received treatment.
      Factors associated with an increased risk of death in refusers included age >= 75
      years, insured monthly salary >= 22,801 NTD, low-income household or aboriginal
      status, and advanced cancer stage (especially stage IV; HR, 11.33). CONCLUSION:
      Our results show a lower 5-year survival for colorectal patients who refused
      treatment than for those who underwent treatment within 4 months. An age of 75
      years or older, low-income household status, advanced stages of cancer,
      especially stage IV, were associated with higher risks of death for those who
      refused treatment.

PMID- 24938669
TI  - Effect of breast cancer phenotype on diagnostic performance of MRI in the
      prediction to response to neoadjuvant treatment.
AB  - AIM: The estimation of response to neoadjuvant chemotherapy (NAC) is useful in
      the surgical decision in breast cancer. We addressed the diagnostic reliability
      of conventional MRI, of diffusion weighted imaging (DWI) and of a merged
      criterion coupling morphological MRI and DWI. Diagnostic performance was analysed
      separately in different tumor subtypes, including HER2+ (human epidermal growth
      factor receptor 2)/HR+ (hormone receptor) (hybrid phenotype). MATERIALS AND
      METHODS: Two-hundred and twenty-five patients underwent MRI before and after NAC.
      The response to treatment was defined according to the RECIST classification and
      the evaluation of DWI with apparent diffusion coefficient (ADC). The complete
      pathological response - pCR was assessed (Mandard classification). RESULTS: Tumor
      phenotypes were Luminal (63.6%), Triple Negative (16.4%), HER2+ (7.6%) or Hybrid
      (12.4%). After NAC, pCR was observed in 17.3% of cases. Average ADC was
      statistically higher after NAC (p<0.001) among patients showing pCR vs. those who
      had not pCR. The RECIST classification showed adequate performance in predicting
      the pCR in Triple Negative (area under the receiver operating characteristic
      curve, ROC AUC=0.9) and in the HER2+ subgroup (AUC=0.826). Lower performance was
      found in the Luminal and Hybrid subgroups (AUC 0.693 and 0.611, respectively),
      where the ADC criterion yielded an improved performance (AUC=0.787 and 0.722).
      The coupling of morphological and DWI criteria yielded maximally improved
      performance in the Luminal and Hybrid subgroups (AUC=0.797 and 0.761).
      CONCLUSION: The diagnostic reliability of MRI in predicting the pCR to NAC
      depends on the tumor phenotype, particularly in the Luminal and Hybrid subgroups.
      In these cases, the coupling of morphological MRI evaluation and DWI assessment
      may facilitate the diagnosis.

PMID- 24938670
TI  - Comment on "impact of a new respiratory amplitude-based gating technique in
      evaluation of upper abdominal PET lesions".

PMID- 24938673
TI  - Deposition of callose in young ovules of two Taraxacum species varying in the
      mode of reproduction.
AB  - Although callose occurs during megasporogenesis in most flowering plants, the
      knowledge about its general function and the mechanisms by which the callose
      layer is formed in particular places is still not sufficient. The results of
      previous studies suggest a total lack of callose in the ovules of diplosporous
      plants in which meiosis is omitted or disturbed. This report is the first
      documentation of callose events in dandelions ovules. We demonstrated the pattern
      of callose deposition during the formation of megaspores through diplospory of
      Taraxacum type and during normal meiotic megasporogenesis in apomictic triploid
      Taraxacum atricapillum and amphimictic diploid Taraxacum linearisquameum. We
      found the presence of callose in the megasporocyte wall of both diplosporous and
      sexual dandelions. However, in a diplosporous dandelion, callose predominated at
      the micropylar pole of megaspore mother cell (MMC) which may be correlated with
      abnormal asynaptic meiosis and may indicate diplospory of the Taraxacum type.
      After meiotic division, callose is mainly deposited in the walls between
      megaspores in tetrads and in diplodyads. In subsequent stages, callose gradually
      disappears around the chalazal functional megaspore. However, some variations in
      the pattern of callose deposition within tetrad may reflect variable positioning
      of the functional megaspore (FM) observed in the ovules of T. linearisquameum. 

PMID- 24938674
TI  - Should health insurers target prevention of cardiovascular disease? A cost
      effectiveness analysis of an individualised programme in Germany based on routine
      data.
AB  - BACKGROUND: Cardiovascular diseases are the main cause of death worldwide, making
      their prevention a major health care challenge. In 2006, a German statutory
      health insurance company presented a novel individualised prevention programme
      (KardioPro), which focused on coronary heart disease (CHD) screening, risk factor
      assessment, early detection and secondary prevention. This study evaluates
      KardioPro in CHD risk subgroups, and analyses the cost-effectiveness of different
      individualised prevention strategies. METHODS: The CHD risk subgroups were
      assembled based on routine data from the statutory health insurance company,
      making use of a quasi-beta regression model for risk prediction. The control
      group was selected via propensity score matching based on logistic regression and
      an approximate nearest neighbour approach. The main outcome was cost
      effectiveness. Effectiveness was measured as event-free time, and events were
      defined as myocardial infarction, stroke and death. Incremental cost
      effectiveness ratios comparing participants with non-participants were calculated
      for each subgroup. To assess the uncertainty of results, a bootstrapping approach
      was applied. RESULTS: The cost-effectiveness of KardioPro in the group at high
      risk of CHD was ? 20,901 per event-free year; in the medium-risk group, ? 52,323
      per event-free year; in the low-risk group, ? 186,074 per event-free year; and in
      the group with known CHD, ? 26,456 per event-free year. KardioPro was associated
      with a significant health gain but also a significant cost increase. However,
      statistical significance could not be shown for all subgroups. CONCLUSION: The
      cost-effectiveness of KardioPro differs substantially according to the group
      being targeted. Depending on the willingness-to-pay, it may be reasonable to only
      offer KardioPro to patients at high risk of further cardiovascular events. This
      high-risk group could be identified from routine statutory health insurance data.
      However, the long-term consequences of KardioPro still need to be evaluated.

PMID- 24938672
TI  - The development and initial validation of a clinical tool for patients'
      preferences on patient participation--The 4Ps.
AB  - AIMS: To report on the development and initial testing of a clinical tool, The
      Patient Preferences for Patient Participation tool (The 4Ps), which will allow
      patients to depict, prioritize, and evaluate their participation in health care.
      BACKGROUND: While patient participation is vital for high quality health care, a
      common definition incorporating all stakeholders' experience is pending. In order
      to support participation in health care, a tool for determining patients'
      preferences on participation is proposed, including opportunities to evaluate
      participation while considering patient preferences. METHODS: Exploratory mixed
      methods studies informed the development of the tool, and descriptive design
      guided its initial testing. The 4Ps tool was tested with 21 Swedish researcher
      experts (REs) and patient experts (PEs) with experience of patient participation.
      Individual Think Aloud interviews were employed to capture experiences of
      content, response process, and acceptability. RESULTS: 'The 4Ps' included three
      sections for the patient to depict, prioritize, and evaluate participation using
      12 items corresponding to 'Having Dialogue', 'Sharing Knowledge', 'Planning', and
      'Managing Self-care'. The REs and PEs considered 'The 4Ps' comprehensible, and
      that all items corresponded to the concept of patient participation. The tool was
      perceived to facilitate patient participation whilst requiring amendments to
      content and layout. CONCLUSIONS: A tool like The 4Ps provides opportunities for
      patients to depict participation, and thus supports communication and
      collaboration. Further patient evaluation is needed to understand the conditions
      for patient participation. While The 4Ps is promising, revision and testing in
      clinical practice is required.

PMID- 24938675
TI  - Electrochemical performance of platinum electrodes within the multi-electrode
      spiral nerve cuff.
AB  - In this study, the electrochemical performance of platinum electrodes within a
      multi-electrode spiral cuff to be used for selective nerve stimulation was
      investigated. The original cuff, simplified into a half-cuff, contained a single
      row of nine electrodes (0.5 * 2 mm) at a distance of 2 mm from its inner surface.
      Cyclic voltammetry was used to investigate the electrochemical reactions at the
      electrode-electrolyte interface, to define a potential window within which the
      electrode could be safely used in selective nerve stimulation, to calculate the
      charge injection capacity and cathodal charge storage capacity. Voltage
      transients retrieved during excitation with quasitrapezoidal biphasic current
      pulses, tested by selective nerve stimulation of the isolated porcine left
      cervical vagus nerve segment, were used to determine the maximum polarization
      across the electrode-electrolyte interface and to calculate cathodic charge
      injection capacity of the electrode. The results show that the most negative and
      most positive potentials across the electrode-electrolyte interface reached -0.54
      and 0.59 V; these did not exceed the safe potential limits for water
      electrolysis. Furthermore, the time integral of the cathodic current by cyclic
      voltammetry measured over the potential range of water electrolysis, actually
      representing the cathodal charge storage capacity, was approximately -4 mC cm(
      2). The charge injection capacity, representing the maximum charge density
      injected in a current stimulation pulse, using only reversible processes,
      however, was around 75 uC cm(-2). In conclusion, both, the tested stimulation
      pulse and electrode are suitable for efficient and safe selective nerve
      stimulation. 

PMID- 24938676
TI  - Ligamentous contributions to pelvic stability in a rotationally unstable open
      book injury: a cadaver study.
AB  - INTRODUCTION: Due to the orientation of the sacroiliac joint (SIJ), as the
      symphysis widens in an open-book pelvic ring disruption, it should displace
      inferiorly. The purposes of this study were to reconfirm this inferior
      displacement and to evaluate the relative contributions of the pubic symphysis
      (PS), the sacrotuberous/sacrospinous ligament complex (STL/SSL) and the anterior
      sacroiliac ligament (ASIL) to pelvic ring stability in a rotationally unstable
      open-book injury. METHODS: For each of 6 cadaver pelves, the right hemipelvis was
      fixed to a table and the PS was sectioned. Under fluoroscopy, a manual external
      rotational force was then applied through the unfixed, left ilium. At the point
      of maximal displacement, a permanent AP image was obtained. With magnification
      corrected, horizontal (H) and vertical (V) displacements were measured. The
      pelves were then divided into two groups of three each. In Group 1, the PS
      release was followed by sectioning of the STL/SSL, and then the ASIL. In Group 2,
      the PS release was followed by sectioning of the ASIL and then the STL/SSL. The
      above described technique of manual manipulation and radiographic measurement was
      repeated after each stage of ligament release. RESULTS: The displacement after
      initial PS sectioning was not significantly different when comparing Group 1 to
      Group 2. In both groups, a significant and progressive increase in displacement
      was noted when the PS (H and V; p<0.05) and ASIL (H and V; p<0.05) were
      sectioned. However, there was no significant change with SSL/STL sectioning in
      either group. Vertical displacements were all directed inferiorly. CONCLUSIONS:
      The PS and ASIL are important in maintaining pelvic ring external rotational
      stability. However, the SSL/STL has little, if any, effect in this regard. Due to
      the orientation of the SIJ, external rotation of the hemipelvis, as in open-book
      injury, will show inferior vertical, as well as horizontal, displacement on the
      AP radiograph, despite the PSIL being intact.

PMID- 24938671
TI  - Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis
      and plasticity are dependent on TNFR1 signaling.
AB  - Patients suffering from neuropathic pain have a higher incidence of mood
      disorders such as depression. Increased expression of tumor necrosis factor (TNF)
      has been reported in neuropathic pain and depressive-like conditions and most of
      the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1).
      Here we sought to investigate: (1) the occurrence of depressive-like behavior in
      chronic neuropathic pain and the associated forms of hippocampal plasticity, and
      (2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of
      such events. Neuropathic pain was induced by chronic constriction injury of the
      sciatic nerve in wild-type and TNFR1(-/-) mice. Anhedonia, weight loss and
      physical state were measured as symptoms of depression. Hippocampal neurogenesis,
      neuroplasticity, myelin remodeling and TNF/TNFRs expression were analyzed by
      immunohistochemical analysis and western blot assay. We found that neuropathic
      pain resulted in the development of depressive symptoms in a time dependent
      manner and was associated with profound hippocampal alterations such as impaired
      neurogenesis, reduced expression of neuroplasticity markers and myelin proteins.
      The onset of depressive-like behavior also coincided with increased hippocampal
      levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all
      fully restored after mice spontaneously recovered from pain. Notably, TNFR1(-/-)
      mice did not develop depressive-like symptoms after injury, nor were there
      changes in hippocampal neurogenesis and plasticity. Our data show that
      neuropathic pain induces a cluster of depressive-like symptoms and profound
      hippocampal plasticity that are dependent on TNF signaling through TNFR1. 

PMID- 24938677
TI  - Responsiveness of SF-36 and Lower Extremity Functional Scale for assessing
      outcomes in traumatic injuries of lower extremities.
AB  - OBJECTIVE: To assess the responsiveness of one generic questionnaire, Medical
      Outcomes Study Short Form-36 (SF-36), and one region-specific outcome measure,
      Lower Extremity Functional Scale (LEFS), in patients with traumatic injuries of
      lower extremities. DESIGN: A prospective and observational study of patients
      after traumatic injuries of lower extremities. Assessments were performed at
      baseline and 3 months later. SETTING: In-patients and out-patients in two
      university hospitals in Taiwan. PARTICIPANTS: A convenience sample of 109
      subjects were evaluated and 94 (86%) were followed. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE(S): Assessments of responsiveness with
      distribution-based approach (effect size, standardized response mean [SRM],
      minimal detectable change) and anchor-based approach (receiver's operating curve
      analysis, ROC analysis). RESULTS: LEFS and physical component score (PCS) of SF
      36 were all responsive to global improvement, with fair-to-good accuracy in
      discriminating between participants with and without improvement. The area under
      curve gained by ROC analysis for LEFS and SF-36 PCS was similar (0.65 vs. 0.70,
      p=0.26). CONCLUSIONS: Our findings revealed comparable responsiveness of LEFS and
      PCS of SF-36 in a sample of subjects with traumatic injuries of lower limbs.
      Either type of functional measure would be suitable for use in clinical trials
      where improvement in function was an endpoint of interest.

PMID- 24938679
TI  - Systematic investigation of the ring-expansion reaction of N-heterocyclic
      carbenes with an iminoborane dihydride.
AB  - Conversions of iminoboranes with an N-heterocyclic carbene (NHC) result in borane
      dihydride formation (BDF) concomitant with dihydrogenated NHC. The iminoborane
      dihydrides are prone to a hydride-mediated ring-expansion reaction (RER) at
      elevated temperature, that is, the insertion of the boron atom into the adjacent
      C?N bond of the NHC to yield boracycles. Upon conversion of a saturated-backbone
      NHC with respective iminoborane precursors RER yet occurs at ambient temperature
      to yield the ring-expanded products. When a less bulky iminoborane is brought in
      contact with sterically unhindered NHC neither the iminoborane dihydride is
      stable at room temperature nor is the RER observed to take place upon heating.
      The conversions of iminoboranes with very bulky NHC do not show BDF at ambient
      temperature and only in the case of the less hindered borane precursor the RER is
      found to proceed in a controlled fashion upon heating. 

PMID- 24938678
TI  - Volume of resected stomach as a predictor of excess weight loss after sleeve
      gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity for the
      treatment of obesity. The objective of this study was to evaluate the volume of
      the resected stomach (VRS) as a predictor of the percentage of excess weight loss
      (%EWL) 1 year after LSG. METHODS: This was a single-surgeon study of
      prospectively collected data of patients who underwent LSG at Jordan University
      Hospital (February 2009 to February 2012). The VRS was measured using a
      standardized technique. The %EWL was calculated at 3, 6, and 12 months
      postoperatively. The correlation between the VRS and %EWL was statistically
      evaluated. RESULTS: Ninety patients underwent LSG during the study period. Of
      these, 73 patients (57 female) completed at least 1 year of follow-up and were
      analyzed; their body mass index was 45 +/- 7.6 kg/m(2) (33-81). The VRS was
      1,337.4 +/- 435.2 ml (600-2,800). The %EWL was 33.6 +/- 11.1 % at 3 months, 48.6
      +/- 15.5 % at 6 months, and 56.8 +/- 18.9 % at 12 months. A significant
      correlation was observed between the VRS and %EWL at 1 year (p = 0.003). Patients
      with a VRS of >1,100 ml (n = 43) achieved significantly greater %EWL at 12 months
      than did those with a VRS of <= 1,100 (n = 30). Removal of >1,100 ml of gastric
      volume was associated with a sensitivity and specificity of 75.5 and 46.2 %,
      respectively, for achieving a %EWL of >= 50 %. CONCLUSION: The VRS can be used as
      an indicator of excess weight loss 1 year after LSG.

PMID- 24938681
TI  - [Endoscopic submucosal resection of small neuroendocrine rectal tumors].

PMID- 24938680
TI  - [Redo intervention and complication management in bariatric surgery].
AB  - Morbid obesity and the associated comorbidities are rapidly increasing worldwide.
      Bariatric surgery has proven to be an effective treatment option. In 2011 more
      then 340,000 bariatric procedures were performed worldwide which is accompanied
      by a growing demand for revision bariatric procedures due to complications or
      failure, such as insufficient weight loss or weight regain.Redo operation
      procedures as well as the management of complications require a profound
      preoperative medical history and diagnostic investigation in combination with an
      exact knowledge of the anatomical changes made in the primary procedure. 

PMID- 24938682
TI  - [Obituary prof. Dr. Volker Bay].

PMID- 24938683
TI  - MaMP and FeMP: computational mesh phantoms applied for studying the variation of
      WBC efficiency using a NaI(Tl) detector.
AB  - In a previous study, the counting efficiency calibration was calculated for 36
      computational mesh phantoms called MaMP and FeMP-Male and Female Mesh Phantoms,
      which span variations in height, weight and gender. They were created to be used
      in a sitting configuration WBC set-up using an HPGe detector. Now this work is
      extended to investigate the influence of body sizes and the position of the
      detector on the counting efficiency (CE) for a different counting geometry. This
      was done by creating a new set of MaMP and FeMP mesh phantoms lying on a
      reclining chair and by studying the variation of the counting efficiency using a
      NaI(Tl) detector for the WBC set-up of SCK-CEN. The deviation of the CE due to
      the detector's position with respect to the phantom was investigated.
      Correlations were also studied for CE as a function of trunk volume, waist-hips
      ratio (WHR) and waist-chest ratio (WCR) for different mesh phantoms. 

PMID- 24938684
TI  - Transgelin overexpression in lung adenocarcinoma is associated with tumor
      progression.
AB  - Hypoxia is a common feature of solid tumors and is associated with an increased
      likelihood of local recurrence and distant metastasis. Transgelin (TAGLN) is an
      actin cross-linking/polymerization protein that belongs to the family of actin
      associated proteins, and there is evidence that TAGLN may be involved in the
      migration of epithelial cells by interacting with actin or promoting podosome
      formation. Cell migration is a key step of cancer metastatis. Thus, the aim of
      this study was to investigate the potential link between TAGLN protein levels and
      hypoxia in lung adenocarcinoma cells and to explore the possible functions and
      expression patterns of TAGLN in lung adenocarcinoma. We first examined the
      effects of altered TAGLN expression on cell migration under both normoxic and
      hypoxic conditions. Immunohistochemical (IHC) staining was also performed to
      examine TAGLN protein expression patterns in lung adenocarcinoma samples. Our
      results revealed that TAGLN was upregulated in the hypoxic lung adenocarcinoma
      cells. The inhibition of TAGLN expression in the cells using small interfering
      RNA (siRNA) led to a decreased migration ability. TAGLN was significantly
      overexpressed in the lung adenocarcinoma tissues compared to the adjacent tumor
      free tissues. A high TAGLN expression correlated with an advanced TNM stage,
      lymph node metastasis and greater differentiation. TAGLN was upregulated in the
      human lung adenocarcinoma cell lines under hypoxic conditions, which contributed
      to the migration ability of the cells. Thus, our data suggest that TAGLN may be a
      viable therapeutic target and a potential biomarker for predicting the prognosis
      of patients with lung adenocarcinoma.

PMID- 24938685
TI  - Retarding the senescence of human vascular endothelial cells induced by hydrogen
      peroxide: effects of 17beta-estradiol (E2) mediated mitochondria protection.
AB  - This study investigates the influence of 17beta-estradiol (E2) on hydrogen
      peroxide (H2O2)-induced human vascular endothelial cell (HUVEC) senescence.
      HUVECs were divided into four groups, namely control group, H2O2 stimulation
      group, E2 intervention group and ICI182780 (ICI) intervention group. The aging
      related beta-galactosidase activities, cytochrome C oxidase activities,
      intracellular ATP levels, intracellular reactive oxygen species (ROS) levels and
      phosphorylated Rb protein expressions were mainly observed. Of which, senescence
      associated beta-galactosidase activities were detected using immunohistochemical
      staining, cytochrome C oxidase activities and intracellular ATP levels were
      detected using commercial kits, ROS levels were detected by fluorescence
      microscopy and fluorescence microplate reader, immunoblotting was used to
      quantitatively detect the expressions of phosphorylated Rb proteins. After
      continuous treatment of H2O2, the senescent phenotypes appeared in the HUVECs.
      The percentage of positive SA-betagal staining cells and the phosphorylated Rb
      expressions were significantly increased; intracellular ROS levels, cytochrome C
      oxidase activities and intracellular ATP levels were elevated. Compared with the
      H2O2 stimulation group, E2 intervention significantly decreased the positive rate
      of SA-beta-gal staining, the phosphorylated Rb protein levels, the intracellular
      ROS levels, cytochrome C oxidase activities and intracellular ATP levels.
      Pretreatment of estrogen receptor blocker ICI182780 weakened the role of E2.
      These results indicated that H2O2 could induce HUVEC senescence; 17beta-E2 might
      relieve H2O2-induced mitochondrial damage through estrogen receptor and delay the
      vascular endothelial cell senescence. 

PMID- 24938686
TI  - The harms and benefits of modern screening mammography.

PMID- 24938687
TI  - Triple-layer midface lifting: long-term follow-up of an effective approach to
      aesthetic surgery of the lower eyelid and the midface.
AB  - BACKGROUND: It is becoming more and more accepted that better aesthetic results
      can be obtained when the lower eyelid is considered as part of the midface when
      contemplating surgical rejuvenation. Descent of the orbicularis muscle and
      midface tissue causes malar bags, loss of volume over the tear-trough, apparent
      vertical lengthening of the lower eyelid, and an accentuation of the orbit-cheek
      junction. METHODS: We describe a triple-layer technique that effectively corrects
      these problems, performed under local anesthesia and via a standard subciliary
      incision, to separately reposition the postseptal fat, suborbicularis oculi fat,
      and the musculocutaneous layer of skin and orbicularis oculi. We present a
      detailed analysis of the complications arising from a series of over 500
      patients, in which this technique has been performed by the senior author.
      RESULTS: The average patient age at the time of surgery was 51 years old (+/-
      7.9), with a median follow-up of 7 months (range 3-121). Complications were
      observed in 77 of 512 cases. In total, 44 of these cases required surgical
      reintervention under local anesthesia (rated as major complications and all
      reinterventions lasted <30 min) and 33 cases were treated conservatively (minor
      complications). CONCLUSION: The triple-layer midface lift is an effective way to
      reverse the combination of ptosis and changes in volume of the aging midface. It
      yields long-lasting results with a minimal risk for complications, particularly
      when a tarsal tuck is performed simultaneously in patients at high risk for the
      development of scleral show. LEVEL OF EVIDENCE V: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 24938688
TI  - A global update on breast implants.

PMID- 24938689
TI  - Augmentation mastopexy: maximal reduction and stable implant coverage using four
      flaps.
AB  - BACKGROUND: A single-stage operation to correct ptotic and hypoplastic breasts
      would appear to be a very appealing option for both surgeons and patients.
      However, this procedure is the most often litigated in aesthetic surgery because
      of its frequent complications. Our goal in this article is to report our
      experience with a four-flap technique for implant coverage in maximum reduction
      mastopexy with prosthesis. METHODS: From January 2011 to March 2013, a total of
      41 patients with Regnault grade II or grade III ptosis with no hypertrophy
      underwent primary bilateral augmentation mastopexy. Our technique includes an
      inverted-T mastopexy and a thin, well-vascularized, inferior dermoglandular flap
      to cover the inferior pole of the implant. Retrospective data collection revealed
      a mean patient age of 37.5 years. Thirty-nine patients were treated with round
      cohesive silicone gel implants and two with anatomical cohesive gel implants. The
      mean implant volume was 280 cc and mean follow-up time was 14 months. RESULTS:
      The following complications were observed in declining frequency: four suture
      dehiscences, two hematomas, one capsular contracture, one implant malposition,
      and one poor scarring. A satisfaction questionnaire revealed very high
      satisfaction in 23 patients (56.09 %), high satisfaction in 12 (29.26 %),
      moderate satisfaction in four (9.75 %), and low satisfaction in two (4.87 %).
      CONCLUSIONS: Our results demonstrated a low complication rate (21.9 %) and low
      reoperation rate (12.1 %) with our technique and make us confident in
      recommending this technique for grade II and grade III ptosis. LEVEL OF EVIDENCE
      V: This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors at
      www.springer.com/00266 .

PMID- 24938690
TI  - Demineralized bone-fibrin sandwich for genioplasty.
AB  - Osseous genioplasty is a versatile technique to improve chin and facial
      aesthetics. It carries several benefits compared to an alloplastic implant, but
      the downsides of an intersegmental gap and lateral stepoffs must be weighed.
      These areas are typically left open, despite being subject to unpredictable
      resorption or incomplete osseous healing. We describe the strategy of using a
      combination of demineralized bone matrix (DBM) and fibrin glue to promote bone
      fill while smoothing contours and transitions along the genioplasty. Our
      retrospective study included 32 patients who underwent genioplasty with the DBM
      fibrin sandwich. There were no genioplasty-related complications at the 6 months
      follow-up. Our results indicate that this technique is safe and is a valuable
      addition to possible graft material for genioplasty. LEVEL OF EVIDENCE IV: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors at www.springer.com/00266
      .

PMID- 24938691
TI  - Use of a novel orbicularis oculi muscle overlap method for correction of tear
      trough deformity.
AB  - BACKGROUND: Although the fat-pad-sliding method reported by Loeb and the "arcus
      marginalis release with preservation of orbital fat" method reported by Hamra are
      useful techniques for correcting tear trough deformity in the Asian population,
      including Japanese patients, occasional cases of tear-trough deformity have
      persisted even after surgery. To solve this problem, the authors developed a
      novel orbicularis oculi muscle overlap method, which has enabled them to obtain
      good results. METHODS: The orbicularis oculi muscle overlap method was performed
      for 10 patients (9 women and 1 man) with prominent tear-trough deformity. The
      average of these patients was 52 years (range, 34-72 years). The origin of the
      orbicularis oculi muscle was elevated at its adherence to the maxillary bone, and
      the innermost portion of the origin of the orbicularis oculi muscle was excised
      by a width of 6 to 7 mm to reduce the muscle tension. This muscle flap was
      overlapped relative to the orbital fat, which was repositioned over the orbital
      rim and sutured in place. RESULTS: Tear-trough deformity improved in all cases,
      and the patients were highly satisfied with their flat lower eyelids. CONCLUSION:
      The orbicularis oculi muscle overlap method is effective for thin eyelids with
      prominent tear-trough deformity. LEVEL OF EVIDENCE V: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 24938692
TI  - Aortic stiffness as a marker of cardiac function and myocardial strain in
      patients undergoing aortic valve replacement.
AB  - BACKGROUND: Cardiac function and myocardial strain are affected by cardiac
      afterload, which is in part due to the stiffness of the aortic wall. In this
      study, we hypothesize that aortic pulse wave velocity (PWV) as a marker of aortic
      stiffness correlates with conventional clinical and biochemical markers of
      cardiac function and perioperative myocardial strain in aortic valve replacement
      (AVR). METHODS: Patients undergoing AVR for aortic stenosis between June 2010 and
      August 2012 were recruited for inclusion in this study. PWV, NYHA class and left
      ventricular (LV) function were assessed pre-operatively. PWV was analysed both as
      a continuous and dichotomous variable according to age-standardized reference
      values. B-type natriuretic peptide (BNP) was measured pre-operatively, and at 3 h
      and 18-24 h after cardiopulmonary bypass (CPB). NYHA class, leg edema, and LV
      function were recorded at follow-up (409 +/- 159 days). RESULTS: Fifty-six
      patients (16 females) with a mean age of 71 +/- 8.4 years were included, with 50
      (89%) patients completing follow-up. The NYHA class of PWV-norm patients was
      significantly lower than PWV-high patients both pre- and post-operatively.
      Multiple logistic regression also highlighted PWV-cut off as an independent
      predictor of NYHA class pre- and post-operatively (OR 8.3, 95% CI [2.27,33.33]
      and OR 14.44, 95% CI [1.49,139.31] respectively). No significant relationship was
      observed between PWV and either LV function or plasma BNP. CONCLUSION: In
      patients undergoing AVR for aortic stenosis, PWV is independently related to pre-
      and post-operative NYHA class but not to LV function or BNP. These findings
      provisionally support the use of perioperative PWV as a non-invasive marker of
      clinical functional status, which when used in conjunction with biomarkers of
      myocardial strain such as BNP, may provide a holistic functional assessment of
      patients undergoing aortic valve surgery. However, in order for PWV assessment to
      be translated into clinical practice and utilised as more than simply a research
      tool, further validation is required in the form of larger prospective studies
      specifically designed to assess the relationship between PWV and these functional
      clinical outcomes.

PMID- 24938693
TI  - Aluminum transfer during dialysis: a systematic review.
AB  - PURPOSE: Dialysis-dependent patients are particularly susceptible to the toxic
      effects of aluminum (Al) because of their impaired ability to eliminate it. Al
      contamination of dialysis fluid remains a threat in this population. The
      mechanism for Al diffusion across dialysis membranes is not well established. Our
      objective is to verify, in AL-exposed patients, the postulate that the direction
      of Al transfer is predicted by the concentration gradient between free diffusible
      plasma Al and dialysate Al. METHODS: A systematic review of the literature was
      performed. Only papers which included Al plasma concentration ([Al]p), Al
      dialysate concentration ([Al]d) and direction of Al transfer (positive = from
      dialysate to plasma, negative = from plasma to dialysate) were selected. We also
      included four patients from our own cohort. Assuming that [Al]p has an
      ultrafiltrable fraction between 17 and 23%, cases were considered in keeping with
      our hypothesis if any of the following scenarios was present: negative Al
      transfer when [Al]d < [Al]p*23% and positive Al transfer when [Al]d > [Al]p*17%.
      RESULTS: The search yielded 409 articles, of which 12 were selected for review.
      When reviewing individual patients for analysis, 108 out of 115 (94%) patients
      followed our hypothesis. By further excluding cases in which Al transfer could
      not be determined, only three out of 111 patients were contrary to out
      hypothesis. CONCLUSION: Comparing ultrafiltrable Al to dialysate Al permits to
      accurately predict the direction of Al transfer. The optimal [Al]d should be <20%
      of the maximally acceptable [Al]p. In order to follow K/DOQI guidelines ([Al]p <
      20 MUg/L), the [Al]d should therefore not exceed 4 MUg/L. At the level presently
      supported by K/DOQI ([Al]d < 10 MUg/L), [Al]p could realistically reach 50 MUg/L
      and potentially cause toxicity.

PMID- 24938695
TI  - Human Participants in Engineering Research: Notes from a Fledgling Ethics
      Committee.
AB  - For the past half-century, issues relating to the ethical conduct of human
      research have focused largely on the domain of medical, and more recently social
      psychological research. The modern regime of applied ethics, emerging as it has
      from the Nuremberg trials and certain other historical antecedents, applies the
      key principles of: autonomy, respect for persons, beneficence, non-maleficence,
      and justice to human beings who enter trials of experimental drugs and devices
      (Martensen in J Hist Med Allied Sci 56(2):168-175, 2001). Institutions such as
      Institutional Review Boards (in the U.S.) and Ethics Committees (in Europe and
      elsewhere) oversee most governmentally-funded medical research around the world,
      in more than a hundred nations that are signers of the Declaration of Helsinki
      (World Medical Association 2008). Increasingly, research outside of medicine has
      been recognized to pose potential risks to human subjects of experiments. Ethics
      committees now operate in the US, Canada, the U.K. and Australia to oversee all
      governmental-funded research, and in other jurisdictions, the range of research
      covered by such committees is expanding. Social science, anthropology, and other
      fields are falling under more clear directives to conduct a formal ethical review
      for basic research involving human participants (Federman et al. in Responsible
      research: a systems approach to protecting research participants. National
      Academies Press, Washington, 2003, p. 36). The legal and institutional response
      for protecting human subjects in the course of developing non-medical
      technologies, engineering, and design is currently vague, but some universities
      are establishing ethics committees to oversee their human subjects research even
      where the experiments involved are non-medical and not technically covered by the
      Declaration of Helsinki. In The Netherlands, as in most of Europe, Asia, Latin
      America, or Africa, no laws mandate an ethical review of non-medical research.
      Yet, nearly 2 years ago we launched a pilot ethics committee at our technical
      university and began soliciting our colleagues to submit their studies for
      review. In the past year, we have become officially recognized as a human
      subjects ethics committee for our university and we are beginning the process of
      requiring all studies using human subjects to apply for our approval. In this
      article, we consider some of the special problems relating to protecting human
      participants in a technology context, and discuss some of our experiences and
      insights about reviewing human subjects research at a technical university,
      concluding: that not less than in medical studies, human participants used in
      technology research benefit from ethical committees' reviews, practical
      requirements for publications, grants, and avoiding legal liability are also
      served by such committees, and ethics committees in such contexts have many
      similarities to, but certain other special foci than medical ethics committees.
      We believe that this experience, and these observations, are helpful for those
      seeking to establish such committees in technology research contexts, and for
      framing the particular issues that may arise in such contexts for the benefit of
      researchers, and nascent committees seeking to establish their own procedures.

PMID- 24938694
TI  - Long-term durability, functional outcomes, and factors associated with surgical
      failure of tension-free vaginal tape procedure.
AB  - PURPOSE: The cure rate of tension-free vaginal tape (TVT) appeared to decrease
      overtime, with an associated increased in the stress urinary incontinence (SUI)
      recurrence rate. We evaluated the long-term durability and functional outcomes of
      TVT and identified the risk factors that may affect recurrence. METHODS: Eighty
      eight patients, who were cured of SUI 6 months after undergoing TVT, were
      followed-up for at least 12 years. At post-operative, the patients were evaluated
      with a Severity Index for Urinary Incontinence questions regarding cure,
      patient's satisfaction, goal achievement, 3-day voiding diary with urinary
      urgency scale, uroflowmetry, and complications. RESULTS: Cure rates decreased
      from 96.6 % at 1-year post-surgery to 83.0 % at 5 years and that the cure rates
      between 5 and 12 year were similar (83.0 vs. 79.6 %). Valsalva leak point
      pressure (VLPP) < 60 H(2)O was the only independent factor that predicted
      recurrence (p = 0.011; hazard radio 5.31). At last follow-up, 39.2 and 70.0 % of
      patients were free of urgency and urgency incontinence, respectively; and de novo
      urgency and urgency incontinence developed in 40.5 and 17.2 % of these patients,
      respectively. Age was the only factor that predicted freedom from overactive
      bladder (OAB) symptom. There was a significant reduction in the maximal flow rate
      from 23.3 +/- 9.0 ml/s pre-operation to 18.8 +/- 6.7 ml/s at 12 years post
      operation. CONCLUSIONS: TVT is an effective long-term treatment for SUI, although
      the cure rate may decrease with time. A low VLPP was predictive of SUI
      recurrence, and patients showing no OAB symptoms tended to be younger.

PMID- 24938697
TI  - Comparison of bivariate and multivariate joint analyses on the selection loss of
      beef cattle.
AB  - For genetic evaluation of beef cattle, univariate or bivariate analyses are often
      performed as an alternative to decrease the complexity of matrices and
      mathematical models compared to multivariate analysis, which considers a larger
      number of joint traits. The use of bivariate methods to calculate genetic
      predictors may cause bias in the estimation of breeding values and, as a
      consequence, reclassification of the rank of top-selected sires, resulting in a
      loss of genetic gain in future generations. The objective of this study was to
      compare the bivariate and multivariate joint methods of genetic evaluation,
      verifying the selection loss, and reclassification of the ranking of the best
      animals with different selection intensities. Records of 431,224 Nellore breed
      animals were evaluated for birth weight, weaning weight, post-weaning gain,
      muscle score, scrotal circumference, and selection index. The pedigree file
      consisted of 505,848 animals, including 218,727 males and 287,121 females. The
      predicted breeding values were obtained using the program PEST 2, and the
      complete pedigree analysis was performed by the PopReport software. The results
      showed that, for the four different selection intensities considered (TOP 10 and
      1, 10, and 30%), selection loss and reclassification of animals in ranking, were
      detected for all traits evaluated when the two methods of analysis were compared.

PMID- 24938696
TI  - Optimizing atoh1-induced vestibular hair cell regeneration.
AB  - OBJECTIVES/HYPOTHESIS: Determine the optimal design characteristics of an
      adenoviral (Ad) vector to deliver atoh1 and induce regeneration of vestibular
      hair cells. STUDY DESIGN: Evaluation of a mouse model of intralabyrinthine gene
      delivery. Tissue culture of mouse and human macular organs. METHODS: Macular
      organs from adult C57Bl/6 mice were treated with binding modified and alternate
      adenovectors expressing green fluorescent protein (gfp) or luciferase (L).
      Expression of marker genes was determined over time to determine vector
      transfection efficiency. The inner ear of adult mice was then injected with
      modified vectors. Expression of gfp and distribution of vector DNA was followed.
      Hearing and balance function was evaluated in normal animals to ensure safety of
      the novel vector designs. An optimized vector was identified and tested for its
      ability to induce hair cell regeneration in a mouse vestibulopathy model.
      Finally, this vector was tested for its ability to induce hair cell regeneration
      in human tissue. RESULTS: Ad5 serotype-based vectors were identified as having a
      variety of different binding capacities for inner ear tissue. This makes it
      difficult to limit the dose of vector due to entry into nontargeted cells.
      Screening of rare adenovector serotypes demonstrated that Ad-based vectors were
      ideally suited for delivery to supporting cells; therefore, they were useful for
      hair cell regeneration studies. Utilization of an Ad28-based vector to deliver
      atoh1 to a mouse model of vestibular loss resulted in significant functional
      recovery of balance. This vector was also capable of transfecting human macular
      organs and inducing regeneration of human vestibular hair cells in vitro.
      CONCLUSIONS: Improvement in vector design can lead to more specific cell-based
      delivery and reduction of nonspecific delivery of the trans gene, leading to the
      development of optimized molecular therapeutics to induce hair cell regeneration.
      LEVEL OF EVIDENCE: N/A. Laryngoscope 124:S1-S12, 2014.

PMID- 24938698
TI  - Construction and functional study of pGN, a mammary gland-specific expression
      plasmid.
AB  - The aim of this study was to construct a mammary gland-specific expression
      vector, pGN, and to validate its function in expressing growth hormone (GH) both
      in vitro and in vivo. First, the GH gene was amplified and inserted downstream of
      the b-casein 5'-arm. Next, the neo gene was cloned downstream of the b-casein 3'
      arm as a selection marker. To analyze the bioactivity of the pGN plasmid, we
      expressed pGN in a Bcap-37 cell line and in the goat mammary gland. Quantitative
      PCR analysis revealed that the expression of GH mRNA in the pGN-transfected group
      was higher than that of the control group in Bcap-37 cells. Results of a
      radioimmunoassay and an enzyme-linked immunosorbent assay demonstrated that the
      pGN-transfected group expressed much more GH protein than the non-transfected
      group (P < 0.05). Upon injection of the pGN plasmid into the goat mammary gland,
      GH mRNA and growth hormone receptor mRNA expressions increased 2-fold. In vivo
      analyses revealed that GH protein expression was higher in the injected group
      than in the control group. Together, these results strongly demonstrated that the
      pGN plasmid was constructed correctly and exhibited favorable bioactivity in
      efficiently expressing GH both in vitro and in vivo. 

PMID- 24938699
TI  - Quantitative genetic study of age at subsequent rebreeding in Nellore cattle by
      using survival analysis.
AB  - The continuous trait age at subsequent rebreeding (ASR) was evaluated using
      survival analysis in Nellore breed cows that conceived for the first time at
      approximately 14 months of age. This methodology was chosen because the
      restricted breeding season produces censored data. The dataset contained 2885
      records of ASR (in days). Records of females that did not produce calves in the
      following year after being exposed to a sire were considered censored (48.3% of
      the total). The statistical model used was a Weibull mixed survival model, which
      included fixed effects of contemporary groups (CG) and period and a random effect
      of individual animal. The effect of contemporary groups on ASR was significant (P
      < 0.01). Heritabilities obtained for ASR were 0.03 and 0.04 in logarithmic and
      original scales, respectively. These results indicate that the genetic selection
      response for subsequent reproduction of 2-year-old Nellore breed females is not
      expected to be effective based on survival analysis. Furthermore, these results
      suggest that environmental improvement is fundamental to this important trait. It
      should be highlighted that an increase in the average date of birth can produce
      an adverse effect in the future, since this cannot be compensated by genetic
      improvement. 

PMID- 24938701
TI  - Study on the treatment of the p15 gene combined with Bcr-abl-specific siRNA and
      STI571 for chronic myeloid leukemia.
AB  - The aim of this study was to investigate the effect of the p15 gene combined with
      Bcr-abl-specific siRNA and STI571 on the proliferation, cell cycle and apoptosis
      of K562 chronic myeloid leukemia cells. Using the gene sequence results, we
      amplified the p15 gene from normal peripheral blood by RT-PCR, and constructed a
      p15-pcDNA3.1 vector. The K562 cell line with G418 resistance was screened,
      synthesized and transfected for bcr-abl gene fusion point for 21-nt siRNA. In p15
      pcDNA3.1-K562 cells, the growth rate was slower than that of the control K562
      cells, G0/G1-phase was increased and S-phase was decreased significantly. In the
      siRNA group, bcr-abl fusion gene expression was significantly decreased in K562
      cells accompanied by the downregulation of BCL-xL protein expression and G1-phase
      arrest. Cell survival rate was significantly decreased compared with the sole p15
      K562 cell group and the sole RNA interference-K562 cell group. In the combination
      of p15-pcDNA3.1-K562 cells with STI571, the proportion of apoptosis was
      significantly increased and the cell survival rate was significantly decreased
      compared with the p15-K562 cell group and STI571-K562 cell group. siRNA at 30 pM
      combined with 0.5 MUM STI571 promoted apoptosis compared with sole application.
      The p15 gene combined with siRNA had a synergistic effect on the inhibition of
      proliferation and the induction of apoptosis in K562 cells. Exogenous p15 protein
      expression combined with STI571 appeared to have a synergistic effect on
      proliferation inhibition and apoptosis induction in K562 cells. The combination
      of low-dose RNA interference with STI571 showed a synergistic effect in inducing
      apoptosis. 

PMID- 24938700
TI  - Fas/FasL in the immune pathogenesis of severe aplastic anemia.
AB  - Fas/FasL protein expression of bone marrow hematopoietic cells was investigated
      in severe aplastic anemia (SAA) patients. Fas expression was evaluated in
      CD34(+), GlycoA(+), CD33(+), and CD14(+) cells labeled with monoclonal antibodies
      in newly diagnosed and remission SAA patients along with normal controls. FasL
      expression was evaluated in CD8(+) cells in the same manner. In CD34(+) cells,
      Fas expression was significantly higher in the newly diagnosed SAA group (46.59
      +/- 27.60%) than the remission (6.12 +/- 3.35%; P < 0.01) and control (8.89 +/-
      7.28%; P < 0.01) groups. In CD14(+), CD33(+), and GlycoA(+) cells, Fas levels
      were significantly lower in the newly diagnosed SAA group (29.29 +/- 9.23, 46.88
      +/- 14.30, and 15.15 +/- 9.26%, respectively) than in the remission (47.23 +/-
      31.56, 67.22 +/- 34.68, and 43.56 +/- 26.85%, respectively; P < 0.05) and normal
      control (51.25 +/- 38.36, 72.06 +/- 39.88, 50.38 +/- 39.88%, respectively; P <
      0.05) groups. FasL expression of CD8(+) cells was significantly higher in the
      newly diagnosed SAA group (89.53 +/- 45.68%) than the remission (56.39 +/-
      27.94%; P < 0.01) and control (48.63 +/- 27.38%; P <0.01) groups. No significant
      differences were observed between the remission and control groups. FasL
      expression in CD8(+) T cells was significantly higher in newly diagnosed
      patients, and CD34(+), CD33(+), CD14(+), and GlycoA(+) cells all showed Fas
      antigen expression. The Fas/FasL pathway might play an important role in
      excessive hematopoietic cell apoptosis in SAA bone marrow. Furthermore, CD34(+)
      cells are likely the main targets of SAA immune injury. 

PMID- 24938702
TI  - Comparison of computed tomography and magnetic resonance imaging in the
      evaluation of facet tropism and facet arthrosis in degenerative cervical
      spondylolisthesis.
AB  - The aim of this study was to determine the reliability of magnetic resonance
      imaging (MRI) in the assessment of facet tropism and facet arthrosis of
      spondylolisthesis levels in degenerative cervical spondylolisthesis as compared
      to computed tomography (CT). The discrepancies in the interpretation of CT and
      MRI data in the evaluation of facet tropism and arthrosis have given rise to
      questions regarding the reliability of comparisons of the two techniques. Using a
      4-point scale, 3 blinded readers independently graded the severity of facet
      tropism and facet arthrosis of 79 cervical facet joints on axial T2-weighted and
      sagittal T1 and T2-weighted turbo spin echo images as well as the corresponding
      axial CT scans. All results were subjected to the kappa coefficient statistic for
      strength of agreement. In the assessment of the severity of facet arthrosis,
      intermethod agreement (weighted kappa) between CT scanning with a moderate inter
      rater reliability (range kappa = 0.43-0.57) and MRI with fair inter-rater
      reliability (range kappa = 0.23-0.38) was 0.76 and 0.43 for the severity of facet
      tropism and facet arthrosis, respectively. Intra-rater reliability for the
      severity of facet arthrosis was moderate to substantial for CT and was moderate
      for MRI scans. Intra-rater reliability for the severity of facet tropism was
      substantial to very good for CT and substantial for MRI scans. MRI can reliably
      determine the presence or degree of facet tropism but not facet arthrosis.
      Therefore, for a comprehensive assessment of cervical facet joint degeneration,
      both a CT and an MRI scan should be performed. 

PMID- 24938703
TI  - Analysis of the genetic variability and structure of Ochlerotatus taeniorhynchus
      (Diptera: Culicidae) populations from the Colombian Atlantic coast on the basis
      of random amplified polymorphic DNA markers.
AB  - Ochlerotatus taeniorhynchus (Diptera: Culicidae) is a mosquito, which is an
      efficient vector of the virus causing epidemic-epizootic Venezuelan equine
      encephalitis in Colombia. This study used 9 random amplified polymorphic DNA
      (RAPD) markers to analyze the mosquito's genetic variability and genetic
      structure of 122 specimens in 7 populations from the Colombian Atlantic coast.
      Assuming that all loci were in Hardy-Weinberg equilibrium, diversity statistics
      and analyses were performed. The average number of amplified fragments for each
      primer was 8.3, and the size of these fragments ranged from 350 to 3600 bp. The
      expected average heterozygosity was 0.358 +/- 0.103. The genetic heterogeneity
      among the populations studied was small (GST = 0.05 +/- 0.01); meanwhile, the
      gene flow estimates (Nm = 7.32 +/- 1.35) were high. In an identical way, the
      Nei's genetic distances obtained yielded very small values amongst the
      populations that were studied in this Colombian region. Furthermore, a spatial
      autocorrelation analysis with Moran's I index revealed a very weak, or
      inexistent, spatial genetic structure among these populations. The comparison of
      these results with those performed for other markers (isoenzymes and
      microsatellites) in populations of this same mosquito from the Colombian Atlantic
      coast was discussed. The results of our RAPD analysis showed scarce genetic
      differentiation among the mosquito populations on the Colombian Atlantic coast,
      which was probably determined by high gene flow levels. 

PMID- 24938704
TI  - Effectiveness of olfactory ensheathing cell transplantation for treatment of
      spinal cord injury.
AB  - The aim of this study was to determine the effectiveness and safety of
      transplantation of olfactory ensheathing cells for functional repair of the
      spinal cord. An olfactory bulb was obtained from a 4- to 5-month-old aborted
      fetus, and it was digested into single olfactory ensheathing cells and then
      cultured and purified for 1 to 2 weeks. Under general anesthesia, these single
      cell suspensions of olfactory ensheathing cells were injected into the
      corresponding spinal injury site with 0.45-mm-diameter injections. The American
      Spinal Injury Association (ASIA) Impairment Scale was used to evaluate spinal
      function. A total of 15 patients (12 men, 3 women; age range, 18-56 years; mean
      age, 40) were admitted for obsolete spinal injuries. Spinal functions of the 15
      patients were observed and followed postoperatively for a period ranging from 2
      weeks to 1 month. All the 15 patients exhibited improvements in spinal function,
      and the improvement tendencies continued. Twelve patients had obvious spinal
      function improvement, and three had slight improvement according to the ASIA
      scale, with an obvious difference between preoperation and postoperation measures
      (P < 0.05). No fevers, infections, functional deteriorations, or deaths were
      seen. Thus, transplantation of olfactory ensheathing cells promoted spinal and
      neurofunctional recovery in patients with malignant spinal injuries, and this
      therapeutic method was safe. 

PMID- 24938705
TI  - Identification and authentication of Rosa species through development of species
      specific SCAR marker(s).
AB  - Roses (Rosa indica) belong to one of the most crucial groups of plants in the
      floriculture industry. Rosa species have special fragrances of interest to the
      perfume and pharmaceutical industries. The genetic diversity of plants based on
      morphological characteristics is difficult to measure under natural conditions
      due to the influence of environmental factors, which is why a reliable
      fingerprinting method was developed to overcome this problem. The development of
      molecular markers will enable the identification of Rosa species. In the present
      study, randomly amplified polymorphic DNA (RAPD) analysis was done on four Rosa
      species, Rosa gruss-an-teplitz (Surkha), Rosa bourboniana, Rosa centifolia, and
      Rosa damascena. A polymorphic RAPD fragment of 391 bp was detected in R.
      bourboniana, which was cloned, purified, sequenced, and used to design a pair of
      species-specific sequence-characterized amplified region (SCAR) primers (forward
      and reverse). These SCAR primers were used to amplify the specific regions of the
      rose genome. These PCR amplifications with specific primers are less sensitive to
      reaction conditions, and due to their high reproducibility, these species
      specific SCAR primers can be used for marker-assisted selection and
      identification of Rosa species. 

PMID- 24938706
TI  - Aberrant DNA methylation of MGMT and hMLH1 genes in prediction of gastric cancer.
AB  - We aimed to explore the association between aberrant DNA methylation of the O(6)
      methylguanine-DNA methyltransferase (MGMT) and human mutL homolog 1 (hMLH1) genes
      with gastric cancer. A total of 283 gastric cancer patients who were confirmed by
      pathological diagnosis were included in our study. Aberrant DNA methylation of
      MGMT and hMLH1 were detected. The proportions of DNA hypermethylation in MGMT and
      hMLH1 in cancer tissues were significantly higher than those in remote normal
      appearing tissues. The DNA hypermethylation of MGMT was correlated with the tumor
      necrosis-metastasis stage in gastric cancer tissues. Results showed that
      individuals with gastric cancer in the N1 and M1 stages had a significantly
      higher risk of DNA hypermethylation of MGMT in cancer tissues [odds ratio (OR) =
      1.97, 95% confidence interval (CI) = 1.15-3.37 for the N1 stage; OR (95%CI) =
      5.39 (2.08-14.98) for the M1 stage]. In conclusion, we found that aberrant
      hypermethylation of MGMT could be a predictive biomarker for detecting gastric
      cancer. 

PMID- 24938707
TI  - Insulin-like growth factor binding protein-3 (IGFBP-3) genetic variant and the
      risk of esophageal squamous cell carcinoma in a Chinese population.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) exerts anti-proliferative
      or pro-apoptotic effects through IGF-dependent as well as IGF-independent
      mechanisms in vitro. The purpose of this study was to examine the association
      between genetic variants in IGFBP-3 (rs2270628) and the risk of esophageal
      squamous cell carcinoma (ESCC) in a Chinese Han population. Five hundred ESCC
      cases and 500 cancer-free controls of the Chinese Han population were involved in
      this study. The IGFBP-3 single-nucleotide polymorphism (SNP) rs2270628 was
      genotyped and the estimated adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) for its association with the risk of ESCC were determined using
      unconditional logistic regression analysis. Compared with the rs2270628 CC
      genotype, TT genotype was associated with a significantly increased ESCC risk
      with OR (95%CI) of 2.07 (1.05-4.09), but CT genotype was not (OR = 1.25, 95%CI
      =0.94-1.66). IGFBP-3 SNP rs2270628 may contribute to the risk of ESCC in the
      Chinese Han population. 

PMID- 24938709
TI  - Development of anti-adhesive spongy sheet composed of hyaluronic acid and
      collagen containing epidermal growth factor.
AB  - Anti-adhesive products need to be designed while considering the concept of wound
      healing. Two main events must proceed simultaneously: facilitating wound healing
      in surgically excised tissue, as well as preventing injured tissue from adhering
      to the surrounding tissue. The present study aimed to develop an anti-adhesive
      spongy sheet composed of hyaluronic acid and collagen (Col) containing epidermal
      growth factor, and to investigate the potential of this spongy sheet using an in
      vitro wound surface model (placing a spongy sheet on a fibroblast-incorporating
      Col gel sheet) and an in vitro inter-tissue model (placing a spongy sheet between
      two fibroblast-incorporating Col gel sheets). These in vitro experiments
      demonstrated that this spongy sheet effectively stimulates fibroblasts to release
      an increased amount of vascular endothelial growth factor and hepatocyte growth
      factor, which are essential for wound healing to proceed succesfully. In
      addition, anti-adhesive performance of this spongy sheet was evaluated in animal
      experiments using Sprague Dawley rats. Under anesthesia, a 1 cm * 2 cm segment of
      peritoneum was superficially excised from walls, and the cecum was then abraded
      by scraping with a scalpel blade over a 1 cm * 2 cm area. A piece of spongy sheet
      was placed on the peritoneal defect. Both defects were placed in contact, and the
      incision was closed by suturing. Peritoneal condition was evaluated after one
      week. This spongy sheet was capable of facilitating the wound healing of
      surgically excised tissue and preventing surgically excised tissue from adhering
      to surrounding tissues.

PMID- 24938708
TI  - Expression of steroidogenic enzymes in human sebaceous glands.
AB  - Androgens are well known to influence sebum synthesis and secretion. Various
      factors related to androgen biosynthesis are expressed in human sebaceous glands.
      In this study, immunohistochemical analysis of human skin specimens from 43
      subjects indicated that various androgen-producing and -metabolizing enzymes were
      functionally localized to sebocytes accumulating lipid droplets and that the
      exclusive expression of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2
      (HSD17B2)) in sebaceous glands was negatively correlated with that of peroxisome
      proliferator-activated receptor gamma (PPARgamma (PPARG)), which also
      significantly changed in an age-dependent manner. We also demonstrated that the
      changes of 17beta-HSD2 expression in human immortalized sebocytes (SZ95)
      influenced the expressions of sebogenesis-related factors. In addition, the
      overexpression of 17beta-HSD2 in SZ95 significantly increased the androstenedione
      production and markedly decreased the amounts of testosterone and
      dihydrotestosterone when DHEA was added externally. On the other hand, the
      phosphorylation of mammalian target of rapamycin, which is well known to induce
      sebum secretion and the onset and/or aggravation of acne, was increased by the
      addition of testosterone in the presence of IGF1 in hamster sebocytes. These
      results all indicated that local androgen biosynthesis and metabolism in human
      sebaceous glands could play a pivotal role in sebum synthesis and secretion. 

PMID- 24938710
TI  - Mechanisms of chromate adsorption on boehmite.
AB  - Adsorption reactions play an important role in the transport behavior of
      groundwater contaminants. Molecular-scale information is needed to elucidate the
      mechanisms by which ions coordinate to soil mineral surfaces. In this study, we
      characterized the mechanisms of chromate adsorption on boehmite (gamma-AlOOH)
      using a combination of extended X-ray absorption fine structure (EXAFS)
      measurements, in situ attenuated total reflectance Fourier transform infrared
      spectroscopy, and quantum chemical calculations. The effects of pH, ionic
      strength, and aqueous chromate concentration were investigated. Our overall
      findings were that chromate primarily forms outer-sphere complexes on boehmite
      over a broad range of pH and aqueous concentrations. Additionally, a small
      fraction of monodentate and bidentate inner-sphere complexes are present under
      acidic conditions, as evidenced by two sets of chromate stretching vibrations at
      approximately 915, 870, and 780cm(-1), and 940, 890, 850, and 780cm(-1),
      respectively. The bidentate complex is supported by a best-fit CrAl distance in
      the EXAFS of 3.2A. Results from DFT also support the formation of monodentate and
      bidentate complexes, which are predicted to results in Gibbs energy changes of 
      140.4 and -62.5kJmol(-1), respectively. These findings are consistent with the
      intermediate binding strength of chromate with respect to similar oxyanions such
      as sulfate and selenite. Overall, the surface species identified in this work can
      be used to develop a more accurate stoichiometric framework in mechanistic
      adsorption models. 

PMID- 24938711
TI  - B vitamin supplementation improves cognitive function in the middle aged and
      elderly with hyperhomocysteinemia.
AB  - OBJECTIVE: An intervention study was performed to determine if supplement
      containing folic acid, vitamin B6, and vitamin B12 could improve cognitive
      function and lower homocysteine in middle-aged and elderly patients with
      hyperhomocysteinemia. METHODS: One hundred and four participants with
      hyperhomocysteinemia were recruited in Tianjin, China, aged 55-94 years old.
      Fifty-seven individuals with hyperhomocysteinemia were included in the
      intervention group (vitamin B group, which received 800 ug/day of folate, with 10
      mg of vitamin B6 and 25 ug of vitamin B12) and 47 patients in the placebo group.
      The endpoint was the improvement in cognitive function as evaluated by Basic
      Cognitive Aptitude Tests (BCATs). All parameters were measured before and after
      the treatment period of 14 weeks. RESULTS: The BCAT total score and four sub
      tests scores (digit copy, Chinese character rotation, digital working memory, and
      recognition of meaningless figure) of BCAT at 14 weeks significantly increased
      only for the vitamin B group. Serum total homocysteine (tHcy) levels
      significantly decreased in the intervention group, while serum concentrations of
      folate, vitamin B6, and vitamin B12 significantly increased in the intervention
      group. CONCLUSION: The results demonstrated that supplement containing folate,
      vitamin B6, and vitamin B12 in middle-aged and elderly patients with
      hyperhomocysteinemia could improve their cognitive function partly and reduce
      serum tHcy levels.

PMID- 24938712
TI  - Clinical prediction model suitable for assessing hospital quality for patients
      undergoing carotid endarterectomy.
AB  - BACKGROUND: Assessing hospital quality in the performance of carotid
      endarterectomy (CEA) requires appropriate risk adjustment across hospitals with
      varying case mixes. The aim of this study was to develop and validate a
      prediction model to assess the risk of in-hospital stroke or death after CEA that
      could aid in the assessment of hospital quality. METHODS AND RESULTS: Patients
      from National Cardiovascular Data Registry (NCDR)'s Carotid Artery
      Revascularization and Endarterectomy (CARE) Registry undergoing CEA without acute
      evolving stroke from 2005 to 2013 were included. In-hospital stroke or death was
      modeled using hierarchical logistic regression with 20 candidate variables and
      accounting for hospital-level clustering. Internal validation was achieved with
      bootstrapping; model discrimination and calibration were assessed. A total of 213
      (1.7%) primary end point events occurred during 12 889 procedures. Independent
      predictors of stroke or death included age, prior peripheral artery disease,
      diabetes mellitus, prior coronary artery disease, having a symptomatic carotid
      lesion, having a contralateral carotid occlusion, or having New York Heart
      Association Class III or IV heart failure. The model was well calibrated and
      demonstrated moderate discriminative ability (c-statistic 0.65). The NCDR CEA
      score was then developed to support simple, prospective risk quantification in
      the clinical setting. CONCLUSIONS: The NCDR CEA score, comprising 7 clinical
      variables, predicts in-hospital stroke or death after CEA. This model can be used
      to estimate hospital risk-adjusted outcomes for CEA and to assist with the
      assessment of hospital quality.

PMID- 24938713
TI  - Smooth muscle specific Rac1 deficiency induces hypertension by preventing
      p116RIP3-dependent RhoA inhibition.
AB  - BACKGROUND: Increasing evidence implicates overactivation of RhoA as a critical
      component of the pathogenesis of hypertension. Although a substantial body of
      work has established that Rac1 functions antagonize RhoA in a broad range of
      physiological processes, the role of Rac1 in the regulation of vascular tone and
      blood pressure is not fully elucidated. METHODS AND RESULTS: To define the role
      of Rac1 in vivo in vascular smooth muscle cells (vSMC), we generated smooth
      muscle (SM)-specific Rac1 knockout mice (SM-Rac1-KO) and performed
      radiotelemetric blood pressure recordings, contraction measurements in arterial
      rings, vSMC cultures and biochemical analyses. SM-Rac1-KO mice develop high
      systolic blood pressure sensitive to Rho kinase inhibition by fasudil. Arteries
      from SM-Rac1-KO mice are characterized by a defective NO-dependent vasodilation
      and an overactivation of RhoA/Rho kinase signaling. We provide evidence that Rac1
      deletion-induced hypertension is due to an alteration of cGMP signaling resulting
      from the loss of Rac1-mediated control of type 5 PDE activity. Consequently, cGMP
      dependent phosphorylation and binding of RhoA with its inhibitory partner, the
      phosphatase-RhoA interacting protein (p116(RIP3)), are decreased. CONCLUSIONS:
      Our data reveal that the depletion of Rac1 in SMC decreases cGMP-dependent
      p116(RIP3)/RhoA interaction and the subsequent inhibition of RhoA signaling.
      Thus, we unveil an in vivo role of Rac1 in arterial blood pressure regulation and
      a new pathway involving p116(RIP3) that contributes to the antagonistic
      relationship between Rac1 and RhoA in vascular smooth muscle cells and their
      opposite roles in arterial tone and blood pressure.

PMID- 24938715
TI  - Diabetes mellitus potentiates diffuse large B-cell lymphoma via high levels of
      CCL5.
AB  - There is much evidence suggesting that CCL5 is one of the chemoattractant
      cytokines involved in diabetes mellitus (DM) with diffuse large B-cell lymphoma
      (DLBCL). However, the pathological impact is unclear. In the current study, in
      order to improve understanding regarding the role of CCL5 in DM with DLBCL, the
      expression levels of CCL5 mRNA were examined in normal B cells, human DLBCL cell
      lines (Ly1, Ly8 and Ly10) and a mouse DLBCL cell line (A20), as well as those in
      cells cultured with either 5 or 30 mmol/l glucose. A20-CCL5+ (CCL5
      overexpression) and A20-CCL5- (CCL5 knockdown) subclones were obtained through
      cell transduction with a lentiviral vector, and were subcutaneously injected into
      BALB/c DM mice and normal mice. Tumor growth was observed by calculating the
      tumor volume. The results demonstrated that CCL5 mRNA levels in DLBCL cells were
      significantly higher than those in the normal cells (P<0.05); and levels in DLBCL
      cells in 30 mmol/l Glu were significantly higher than in those of DLBCL cells in
      5 mmol/l Glu (P<0.05). A20-CCL5+ cells led to tumor formation in DM mice compared
      with A20 and A20-CCL5- cells. These results indicate that high levels of CCL5
      expression may accelerate DLBCL formation in DM.

PMID- 24938714
TI  - Viral exploitation of actin: force-generation and scaffolding functions in viral
      infection.
AB  - As a fundamental component of the host cellular cytoskeleton, actin is routinely
      engaged by infecting viruses. Furthermore, viruses from diverse groups, and
      infecting diverse hosts, have convergently evolved an array of mechanisms for
      manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus
      of research now indicates that the actin cytoskeleton is critical for viral
      replication at many stages of the viral life cycle, including binding, entry,
      nuclear localization, genomic transcription and reverse transcription, assembly,
      and egress/dissemination. Specifically, viruses subvert the force-generating and
      macromolecular scaffolding properties of the actin cytoskeleton to propel viral
      surfing, internalization, and migration within the cell. Additionally, viruses
      utilize the actin cytoskeleton to support and organize assembly sites, and eject
      budding virions for cell-to-cell transmission. It is the purpose of this review
      to provide an overview of current research, focusing on the various mechanisms
      and themes of virus-mediated actin modulation described therein. 

PMID- 24938718
TI  - Mutations of 60 known causative genes in 157 families with retinitis pigmentosa
      based on exome sequencing.
AB  - Retinitis pigmentosa (RP) is the most common and highly heterogeneous form of
      hereditary retinal degeneration. This study was to identify mutations in the 60
      genes that were known to be associated with RP in 157 unrelated Chinese families
      with RP. Genomic DNA from probands was initially analyzed by whole exome
      sequencing. Sanger sequencing was used to confirm potential candidate variants
      affecting the encoded residues in the 60 genes, including heterozygous variants
      from genes that are related to autosomal dominant RP, homozygous or compound
      heterozygous variants from genes that are related to autosomal recessive RP, and
      hemizygous variants from genes that are related to X-linked RP. Synonymous and
      intronic variants were also examined to confirm whether they could affect
      splicing. A total of 244 candidate variants were detected by exome sequencing.
      Sanger sequencing confirmed 240 variants out of the 244 candidates. Informatics
      and segregation analyses suggested 110 potential pathogenic mutations in 28 out
      of the 60 genes involving 79 of the 157 (50%) families, including 31 (39%, 31/79)
      families with heterozygous mutations in autosomal dominant genes, 37 (47%, 37/79)
      families with homozygous (9) or compound heterozygous (28) mutations in autosomal
      recessive genes, and 11 (14%, 11/79) families with hemizygous mutations in X
      linked genes. Of the 110 identified variants, 74 (67%) were novel. The genetic
      defects in approximately half of the 157 studies families were detected by exome
      sequencing. A comprehensive analysis of the 60 known genes not only expanded the
      mutation spectrum and frequency of the 60 genes in Chinese patients with RP, but
      also provided an overview of the molecular etiology of RP in Chinese patients.
      The analysis of the known genes also supplied the foundation and clues for
      discovering novel causative RP genes.

PMID- 24938721
TI  - Neuroendocrinology: a long pain-free life.

PMID- 24938719
TI  - The role of concentration-effect relationships in the assessment of QTc interval
      prolongation.
AB  - Population pharmacokinetic and pharmacokinetic-pharmacodynamic (PKPD) modelling
      has been widely used in clinical research. Yet, its application in the evaluation
      of cardiovascular safety remains limited, particularly in the evaluation of pro
      arrhythmic effects. Here we discuss the advantages of disadvantages of population
      PKPD modelling and simulation, a paradigm built around the knowledge of the
      concentration-effect relationship as the basis for decision making in drug
      development and its utility as a guide to drug safety. A wide-ranging review of
      the literature was performed on the experimental protocols currently used to
      characterize the potential for QT interval prolongation, both pre-clinically and
      clinically. Focus was given to the role of modelling and simulation for design
      optimization and subsequent analysis and interpretation of the data,
      discriminating drug from system specific properties. Cardiovascular safety
      remains one of the major sources of attrition in drug development with stringent
      regulatory requirements. However, despite the myriad of tests, data are not
      integrated systematically to ensure accurate translation of the observed drug
      effects in clinically relevant conditions. The thorough QT study addresses a
      critical regulatory question but does not necessarily reflect knowledge of the
      underlying pharmacology and has limitations in its ability to address fundamental
      clinical questions. It is also prone to issues of multiplicity. Population
      approaches offer a paradigm for the evaluation of drug safety built around the
      knowledge of the concentration-effect relationship. It enables quantitative
      assessment of the probability of QTc interval prolongation in patients, providing
      better guidance to regulatory labelling and understanding of benefit/risk in
      specific populations. 

PMID- 24938720
TI  - Enzyme replacement therapy attenuates disease progression in a canine model of
      late-infantile neuronal ceroid lipofuscinosis (CLN2 disease).
AB  - Using a canine model of classical late-infantile neuronal ceroid lipofuscinosis
      (CLN2 disease), a study was conducted to evaluate the potential pharmacological
      activity of recombinant human tripeptidyl peptidase-1 (rhTPP1) enzyme replacement
      therapy administered directly to the cerebrospinal fluid (CSF). CLN2 disease is a
      hereditary neurodegenerative disorder resulting from mutations in CLN2, which
      encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Infants with
      mutations in both CLN2 alleles develop normally but in the late-infantile/early
      childhood period undergo progressive neurological decline accompanied by
      pronounced brain atrophy. The disorder, a form of Batten disease, is uniformly
      fatal, with clinical signs starting between 2 and 4 years of age and death
      usually occurring by the early teenage years. Dachshunds homozygous for a null
      mutation in the canine ortholog of CLN2 (TPP1) exhibit a similar disorder that
      progresses to end stage at 10.5-11 months of age. Administration of rhTPP1 via
      infusion into the CSF every other week, starting at approximately 2.5 months of
      age, resulted in dose-dependent significant delays in disease progression, as
      measured by delayed onset of neurologic deficits, improved performance on a
      cognitive function test, reduced brain atrophy, and increased life span. Based on
      these findings, a clinical study evaluating the potential therapeutic value of
      rhTPP1 administration into the CSF of children with CLN2 disease has been
      initiated.

PMID- 24938722
TI  - Cognition: Klotho spins cognitive fate.

PMID- 24938723
TI  - Follow-up of cutaneous melanoma patients: a proposal for standardization.

PMID- 24938725
TI  - Opportunistic deep cutaneous mycoses in solid organ transplant recipients.
AB  - Invasive fungal infections are a major cause of morbidity and mortality among
      organ transplant recipients, despite many progresses concerning diagnosis,
      preventions and treatment. Risk factors for invasive fungal infections in
      transplanted recipients include type and severity of immunosuppression,
      especially in life-saving organs as lung or liver, older age at transplantation,
      and technical complexity of surgery, living in endemic areas or exposure to a
      contaminated environment. Superficial fungal infections are caused by Candida,
      Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a
      consequence of the systemic dissemination of invasive mycoses, or after direct
      inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould
      infections, fusariosis and infections attributable to Scedosporium and
      Pseudallescheria species are the most common etiological agents. Cutaneous
      manifestations of fungal infection are not specific, and a high degree of
      suspicion is required, and prompt biopsy for histology and culture is needed.
      Therapy with lyposomal amphotericin B and new triazoles are effective. 

PMID- 24938726
TI  - Reporting transient molecular events by DNA strand displacement.
AB  - Transient formation of DNA triplexes was reported by coupling with a permanent
      strand displacement reaction. 

PMID- 24938727
TI  - The relationship between US heroin market dynamics and heroin-related overdose,
      1992-2008.
AB  - BACKGROUND AND AIMS: Heroin-related overdose is linked to polydrug use, changes
      in physiological tolerance and social factors. Individual risk can also be
      influenced by the structural risk environment including the illicit drug market.
      We hypothesized that components of the US illicit drug market, specifically
      heroin source/type, price and purity, will have independent effects on the number
      of heroin-related overdose hospital admissions. METHODS: Yearly, from 1992 to
      2008, Metropolitan Statistical Area (MSA) price and purity series were estimated
      from the US Drug Enforcement Administration data. Yearly heroin overdose
      hospitalizations were constructed from the Nationwide Inpatient Sample. Socio
      demographic variables were constructed using several databases. Negative binomial
      models were used to estimate the effect of price, purity and source region of
      heroin on yearly hospital counts of heroin overdoses controlling for poverty,
      unemployment, crime, MSA socio-demographic characteristics and population size.
      RESULTS: Purity was not associated with heroin overdose, but each $100 decrease
      in the price per pure gram of heroin resulted in a 2.9% [95% confidence interval
      (CI) = 4.8%, 1.0%] increase in the number of heroin overdose hospitalizations (P
      = 0.003). Each 10% increase in the market share of Colombian-sourced heroin was
      associated with a 4.1% (95% CI = 1.7%, 6.6%) increase in number of overdoses
      reported in hospitals (P = 0.001) independent of heroin quality. CONCLUSIONS:
      Decreases in the price of pure heroin in the United States are associated with
      increased heroin-related overdose hospital admissions. Increases in market
      concentration of Colombian-source/type heroin is also associated with an increase
      in heroin-related overdose hospital admissions. Increases in US heroin-related
      overdose admissions appear to be related to structural changes in the US heroin
      market.

PMID- 24938728
TI  - Selective vulnerability of the cerebral vasculature to blast injury in a rat
      model of mild traumatic brain injury.
AB  - BACKGROUND: Blast-related traumatic brain injury (TBI) is a common cause of
      injury in the military operations in Iraq and Afghanistan. How the primary blast
      wave affects the brain is not well understood. The aim of the present study was
      to examine whether blast exposure affects the cerebral vasculature in a rodent
      model. We analyzed the brains of rats exposed to single or multiple (three) 74.5
      kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24
      hours or between 6 and 10 months after exposure. Blast-induced cerebral vascular
      pathology was examined by a combination of light microscopy,
      immunohistochemistry, and electron microscopy. RESULTS: We describe a selective
      vascular pathology that is present acutely at 24 hours after injury. The vascular
      pathology is found at the margins of focal shear-related injuries that, as we
      previously showed, typically follow the patterns of penetrating cortical vessels.
      However, changes in the microvasculature extend beyond the margins of such
      lesions. Electron microscopy revealed that microvascular pathology is found in
      regions of the brain with an otherwise normal neuropil. This initial injury leads
      to chronic changes in the microvasculature that are still evident many months
      after the initial blast exposure. CONCLUSIONS: These studies suggest that
      vascular pathology may be a central mechanism in the induction of chronic blast
      related injury.

PMID- 24938729
TI  - What works in practice: user and provider perspectives on the acceptability,
      affordability, implementation, and impact of a family-based intervention for
      child overweight and obesity delivered at scale.
AB  - BACKGROUND: As part of a study considering the impact of a child weight
      management programme when rolled out at scale following an RCT, this qualitative
      study focused on acceptability and implementation for providers and for families
      taking part. METHODS: Participants were selected on the basis of a maximum
      variation sample providing a range of experiences and social contexts.
      Qualitative interviews were conducted with 29 professionals who commissioned or
      delivered the programme, and 64 individuals from 23 families in 3 English
      regions. Topic guides were used as a tool rather than a rule, enabling
      participants to construct a narrative about their experiences. Transcripts were
      analysed using framework analysis. RESULTS: Practical problems such as transport,
      work schedules and competing demands on family time were common barriers to
      participation. Delivery partners often put considerable efforts into recruiting,
      retaining and motivating families, which increased uptake but also increased
      cost. Parents and providers valued skilled delivery staff. Some providers made
      adaptations to meet local social and cultural needs. Both providers and parents
      expressed concerns about long term outcomes, and how this was compromised by an
      obesogenic environment. Concerns about funding together with barriers to uptake
      and engagement could translate into barriers to commissioning. Where these
      barriers were not experienced, commissioners were enthusiastic about continuing
      the programme. CONCLUSIONS: Most families felt that they had gained something
      from the programme, but few felt that it had 'worked' for them. The demands on
      families including time and emotional work were experienced as difficult. For
      commissioners, an RCT with positive results was an important driver, but family
      barriers, alongside concerns about recruitment and retention, a desire for local
      adaptability with qualified motivated staff, and funding changes discouraged some
      from planning to use the intervention in future.

PMID- 24938731
TI  - Development and Validation of the Poker Skills Measure (PSM).
AB  - Existing research has demonstrated that poker is a game predominated by skill.
      Little is known about the specific characteristics of good poker players however,
      likely due in part to the lack of a readily available measure of poker skill. In
      the absence of an available and easily administered poker skill measure,
      laboratory studies of poker player attributes have used questionable
      methodologies to assess skill including peer- and self-report. The aim of the
      current research was to create a valid, reliable, and easily administered measure
      of poker playing skill. A sample of 100 University of Lethbridge undergraduate
      students and Lethbridge community members completed the newly created Poker
      Skills Measure (PSM) and an objective measure of poker playing performance
      (playing virtual poker). External validity of the measure was demonstrated via
      significant associations-expected and detected-between the PSM and the objective
      playing measure. Specifically, significant positive associations were found
      between PSM scores and hands won, pre- and post flop aggression, and a
      significant negative relationship was detected between PSM scores and number of
      hands played. Within the current sample, acceptable internal consistency
      (Cronbach's alpha = .82) and very good test re-test reliability (r = .78) was
      achieved with the 35 item PSM. Future directions are discussed.

PMID- 24938730
TI  - Significant inconsistency among pediatric oncologists in the use of the
      neutropenic diet.
AB  - BACKGROUND: The role of the neutropenic diet in the development of infections in
      oncology and stem cell transplant (SCT) patients is controversial. There is no
      data on the use of the neutropenic diet among pediatric oncologists. METHODS: A
      self-administered electronic survey was sent to 1,639 pediatric oncologists at
      198 institutions who are members of Children's Oncology Group. A pediatric
      dietitian and pediatric oncologists developed, pretested, and modified the survey
      for item clarification. RESULTS: Five hundred fifty-seven physicians (34%)
      responded representing 174 (87%) of the 198 member institutions. More than half
      of respondents (57%) report implementing the neutropenic diet at their facility.
      In a multivariate analysis, being a stem cell transplant (SCT) center was the
      only significant factor associated with implementing a neutropenic diet (OR:
      6.06, 95% CI, 2.88-12.738, P < 0.001) after controlling for years in practice,
      gender, center size, and academic versus private practice. Among physicians who
      implemented a neutropenic diet, absolute neutrophil count was the trigger for
      initiating the diet in oncology patients (72%) while admission and start of
      preparative regimen was used for SCT patients (84%). The majority of respondents
      (82%) stop the neutropenic diet when oncology patients are no longer neutropenic
      while the practice varied significantly with SCT patients. Providers at the same
      institution were not consistent with implementation of the diet, patient
      populations placed on the neutropenic diet and parameters for initiation,
      discontinuation of the diet and specific food restrictions. CONCLUSION: The
      implementation of the neutropenic diet by pediatric oncologists remains quite
      variable even among those at the same institution.

PMID- 24938732
TI  - Decoding Problem Gamblers' Signals: A Decision Model for Casino Enterprises.
AB  - The aim of the present study is to offer a validated decision model for casino
      enterprises. The model enables those users to perform early detection of problem
      gamblers and fulfill their ethical duty of social cost minimization. To this end,
      the interpretation of casino customers' nonverbal communication is understood as
      a signal-processing problem. Indicators of problem gambling recommended by
      Delfabbro et al. (Identifying problem gamblers in gambling venues: final report,
      2007) are combined with Viterbi algorithm into an interdisciplinary model that
      helps decoding signals emitted by casino customers. Model output consists of a
      historical path of mental states and cumulated social costs associated with a
      particular client. Groups of problem and non-problem gamblers were simulated to
      investigate the model's diagnostic capability and its cost minimization ability.
      Each group consisted of 26 subjects and was subsequently enlarged to 100
      subjects. In approximately 95% of the cases, mental states were correctly decoded
      for problem gamblers. Statistical analysis using planned contrasts revealed that
      the model is relatively robust to the suppression of signals performed by casino
      clientele facing gambling problems as well as to misjudgments made by staff
      regarding the clients' mental states. Only if the last mentioned source of error
      occurs in a very pronounced manner, i.e. judgment is extremely faulty, cumulated
      social costs might be distorted.

PMID- 24938735
TI  - Case series and descriptive cohort studies in neurosurgery: the confusion and
      solution.
AB  - BACKGROUND: Case series (CS) are well-known designs in contemporary use in
      neurosurgery but are sometimes used in contexts that are incompatible with their
      true meaning as defined by epidemiologists. This inconsistent, inappropriate and
      incorrect use, and mislabeling impairs the appropriate indexing and sorting of
      evidence. METHOD: Using PubMed, we systematically identified published articles
      that had "case series" in the "title" in 15 top-ranked neurosurgical journals
      from January 2008 to December 2012. The abstracts and/or full articles were
      scanned to identify those with descriptions of the principal method as being
      "case series" and then classified as "true case series" or "non-case series" by
      two independent investigators with 100 % inter-rater agreement. RESULTS: Sixty
      four articles had the label "case series" in their "titles." Based on the
      definition of "case series" and our appraisal of the articles using Strengthening
      the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, 18
      articles (28.13 %) were true case series, while 46 (71.87 %) were mislabeled.
      Thirty-five articles (54.69 %) mistook retrospective (descriptive) cohorts for
      CS. CS are descriptive with an outcome-based sampling, while "descriptive
      cohorts" have an exposure-based sampling of patients, followed over time to
      assess outcome(s). A comparison group is not a defining feature of a cohort study
      and distinguishes descriptive from analytic cohorts. CONCLUSION: A distinction
      between a case report, case series, and descriptive cohorts is absolutely
      necessary to enable the appropriate indexing, sorting, and application of
      evidence. Researchers need better training in methods and terminology, and
      editors and reviewers should scrutinize more carefully manuscripts claiming to be
      "case series" studies.

PMID- 24938736
TI  - Rapid molecular genetic diagnosis of hypertrophic cardiomyopathy by semiconductor
      sequencing.
AB  - BACKGROUND: Rapidly determining the complex genetic basis of Hypertrophic
      cardiomyopathy (HCM) is vital to better understanding and optimally managing this
      common polygenetic cardiovascular disease. METHODS: A rapid custom Ion-amplicon
      resequencing assay, covering 30 commonly affected genes of HCM, was developed and
      validated in 120 unrelated patients with HCM to facilitate genetic diagnosis of
      this disease. With this HCM-specific panel and only 20 ng of input genomic DNA,
      physicians can, for the first time, go from blood samples to variants within a
      single day. RESULTS: On average, this approach gained 595628 mapped reads per
      sample, 95.51% reads on target (64.06 kb), 490-fold base coverage depth and
      93.24% uniformity of base coverage in CDS regions of the 30 HCM genes. After
      validation, we detected underlying pathogenic variants in 87% (104 of 120)
      samples. Tested seven randomly selected HCM genes in eight samples by Sanger
      sequencing, the sensitivity and false-positive-rate of this HCM panel was 100%
      and 5%, respectively. CONCLUSIONS: This Ion amplicon HCM resequencing assay
      provides a currently most rapid, comprehensive, cost-effective and reliable
      measure for genetic diagnosis of HCM in routinely obtained samples.

PMID- 24938734
TI  - Lysine pyrrolation is a naturally-occurring covalent modification involved in the
      production of DNA mimic proteins.
AB  - Covalent modification of proteins exerts significant effects on their chemical
      properties and has important functional and regulatory consequences. We now
      report the identification and verification of an electrically-active form of
      modified proteins recognized by a group of small molecules commonly used to
      interact with DNA. This previously unreported property of proteins was initially
      discovered when the gamma-ketoaldehydes were identified as a source of the
      proteins stained by the DNA intercalators. Using 1,4-butanedial, the simplest
      gamma-ketoaldehyde, we characterized the structural and chemical criteria
      governing the recognition of the modified proteins by the DNA intercalators and
      identified N(epsilon)-pyrrolelysine as a key adduct. Unexpectedly, the
      pyrrolation conferred an electronegativity and electronic properties on the
      proteins that potentially constitute an electrical mimic to the DNA. In addition,
      we found that the pyrrolated proteins indeed triggered an autoimmune response and
      that the production of specific antibodies against the pyrrolated proteins was
      accelerated in human systemic lupus erythematosus. These findings and the
      apparent high abundance of N(epsilon)-pyrrolelysine in vivo suggest that protein
      pyrrolation could be an endogenous source of DNA mimic proteins, providing a
      possible link connecting protein turnover and immune disorders. 

PMID- 24938738
TI  - Treatment outcomes from community-based drug resistant tuberculosis treatment
      programs: a systematic review and meta-analysis.
AB  - BACKGROUND: There is increasing evidence that community-based treatment of drug
      resistant tuberculosis (DRTB) is a feasible and cost-effective alternative to
      centralized, hospital-based care. Although several large programs have reported
      favourable outcomes from community-based treatment, to date there has been no
      systematic assessment of community-based DRTB treatment program outcomes. The
      objective of this study was to synthesize available evidence on treatment
      outcomes from community based multi-drug resistant (MDRTB) and extensively drug
      resistant tuberculosis (XDRTB) treatment programs. METHODS: We performed a
      systematic review and meta-analysis of the published literature to examine
      treatment outcomes from community-based MDRTB and XDRTB treatment programs.
      Studies reporting outcomes from programs using community-based treatment
      strategies and reporting outcomes consistent with WHO guidelines were included
      for analysis. Treatment outcomes, including treatment success, default, failure,
      and death were pooled for analysis. Meta-regression was performed to examine for
      associations between treatment outcomes and program or patient factors. RESULTS:
      Overall 10 studies reporting outcomes on 1288 DRTB patients were included for
      analysis. Of this population, 65% [95% CI 59-71%] of patients had a successful
      outcome, 15% [95% CI 12-19%] defaulted, 13% [95% CI 9-18%] died, and 6% [95% CI 3
      11%] failed treatment for a total of 35% [95% CI 29-41%] with unsuccessful
      treatment outcome. Meta-regression failed to identify any factors associated with
      treatment success, including study year, age of participants, HIV prevalence,
      XDRTB prevalence, treatment regimen, directly observed therapy (DOT) location or
      DOT provider. CONCLUSIONS: Outcomes of community-based MDRTB and XDRTB treatment
      outcomes appear similar to overall treatment outcomes published in three
      systematic reviews on MDRTB therapy. Work is needed to delineate program
      characteristics associated with improved treatment outcomes.

PMID- 24938737
TI  - Impaired structural and functional regeneration of skeletal muscles from beta2
      adrenoceptor knockout mice.
AB  - AIMS: beta2-adrenergic stimulation causes beneficial effects on structure and
      function of regenerating muscles; thus, the beta2-adrenoceptor may play an
      important role in the muscle regenerative process. Here, we investigated the role
      of the beta2 -adrenoceptor in skeletal muscle regeneration. METHODS: Tibialis
      anterior (TA) muscles from beta2-adrenoceptor knockout (beta2 KO) mice were
      cryolesioned and analysed after 1, 3, 10 and 21 days. The role of beta2
      adrenoceptor on regenerating muscles was assessed through the analysis of
      morphological and contractile aspects, M1 and M2 macrophage profile, cAMP
      content, and activation of TGF-beta signalling elements. RESULTS: Regenerating
      muscles from beta2 KO mice showed decreased calibre of regenerating myofibres and
      reduced muscle contractile function at 10 days when compared with those from wild
      type. The increase in cAMP content in muscles at 10 days post-cryolesion was
      attenuated in the absence of the beta2 -adrenoceptor. Furthermore, there was an
      increase in inflammation and in the number of macrophages in regenerating muscles
      lacking the beta2-adrenoceptor at 3 and 10 days, a predominance of M1 macrophage
      phenotype, a decrease in TbetaR-I/Smad2/3 activation, and in the Smad4 expression
      at 3 days, while akirin1 expression increased at 10 days in muscles from beta2 KO
      mice when compared to those from wild type. CONCLUSIONS: Our results suggest that
      the beta2-adrenoceptor contributes to the regulation of the initial phases of
      muscle regeneration, especially in the control of macrophage recruitment in
      regenerating muscle through activation of TbetaR-I/Smad2/3 and reduction in
      akirin1 expression. These findings have implications for the future development
      of better therapeutic approaches to prevent or treat muscle injuries.

PMID- 24938740
TI  - Carbon dioxide-pneumoperitoneum in rats reduces ischemia/reperfusion-induced
      hepatic apoptosis and inflammatory responses by stimulating sensory neurons.
AB  - Laparoscopic surgery induces a milder inflammatory response than open surgery,
      however, the precise mechanisms underlying this phenomenon remain to be
      elucidated. Our previous study demonstrated that stimulation of sensory neurons
      inhibited hepatic apoptosis and inflammatory responses in rats subjected to
      hepatic ischemia/reperfusion (I/R). Since carbon dioxide (CO2) has been
      demonstrated to stimulate sensory neurons, it was hypothesized that CO2
      pneumoperitoneum, as used in laparoscopic surgery, may attenuate inflammatory
      responses by stimulating sensory neurons. This hypothesis was examined using rats
      subjected to hepatic I/R. The rats were subjected to partial hepatic ischemia for
      60 min followed by reperfusion. Abdominal insufflation with CO2 or air was
      performed for 30 min prior to hepatic I/R. Hepatic I/R-induced hepatocellular
      apoptosis and expression of the neutrophil chemoattractant endothelial monocyte
      activated polypeptide-II, were inhibited by CO2-pneumoperitoneum, however, not by
      air-pneumoperitoneum. Pretreatment with the transient receptor potential
      vanilloid 1 antagonist SB366791 reversed the protective effects of CO2
      pneumoperitoneum. The results from the present study demonstrated that CO2
      pneumoperitoneum attenuates hepatic apoptosis and inflammatory responses in rats
      subjected to hepatic I/R, possibly by stimulating sensory neurons. These findings
      suggested that CO2-pneumoperitoneum contributed to the attenuated inflammatory
      response observed following laparoscopic surgery.

PMID- 24938739
TI  - Ordered and kinetically discrete sequential protein release from biodegradable
      thin films.
AB  - Multidrug regimens can sometimes treat recalcitrant diseases when single-drug
      therapies fail. Recapitulating complex multidrug administration from controlled
      release films for localized delivery remains challenging because their release
      kinetics are frequently intertwined, and an initial burst release of each drug is
      usually uncontrollable. Kinetic control over protein release is demonstrated by
      cross-linking layer-by-layer films during the assembly process. We used
      biodegradable and naturally derived components and relied on copper-free click
      chemistry for bioorthogonal covalent cross-links throughout the film that entrap
      but do not modify the embedded protein. We found that this strategy restricted
      the interdiffusion of protein while maintaining its activity. By depositing a
      barrier layer and a second protein-containing layer atop this construct, we
      generated well-defined sequential protein release with minimal overlap that
      follows their spatial distribution within the film. 

PMID- 24938741
TI  - Persistent stimulation of photosynthesis in short rotation coppice mulberry under
      elevated CO2 atmosphere.
AB  - Current study was undertaken to elucidate the responses of short rotation coppice
      (SRC) mulberry under elevated CO2 atmosphere (550MUmolmol(-1)). Throughout the
      experimental period, elevated CO2 grown mulberry plants showed significant
      increase in light saturated photosynthetic rates (A') by increasing intercellular
      CO2 concentrations (Ci) despite reduced stomatal conductance (gs). Reduced gs was
      linked to decrease in transpiration (E) resulting in improved water use
      efficiency (WUE). There was a significant increase in carboxylation efficiency
      (CE) of Rubisco, apparent quantum efficiency (AQE), light and CO2 saturated
      photosynthetic rates (AMAX), photosynthetic nitrogen use efficiency (PNUE),
      chlorophyll a fluorescence characteristics (FV/FM and PIABS), starch and other
      carbohydrates in high CO2 grown plants which clearly demonstrate no
      photosynthetic acclimation in turn resulted marked increase in above and below
      ground biomass. Our results strongly suggest that short rotation forestry
      (<1year) with mulberry plantations should be effective to mitigate raising CO2
      levels as well as for the production of renewable bio-energy. 

PMID- 24938742
TI  - The influence of unsupervised time on elementary school children at high risk for
      inattention and problem behaviors.
AB  - In the last few decades, changing socioeconomic and family structures have
      increasingly left children alone without adult supervision. Carefully prepared
      and limited periods of unsupervised time are not harmful for children. However,
      long unsupervised periods have harmful effects, particularly for those children
      at high risk for inattention and problem behaviors. In this study, we examined
      the influence of unsupervised time on behavior problems by studying a sample of
      elementary school children at high risk for inattention and problem behaviors.
      The study analyzed data from the Children's Mental Health Promotion Project,
      which was conducted in collaboration with education, government, and mental
      health professionals. The child behavior checklist (CBCL) was administered to
      assess problem behaviors among first- and fourth-grade children. Multivariate
      logistic regression analysis was used to evaluate the influence of unsupervised
      time on children's behavior. A total of 3,270 elementary school children (1,340
      first-graders and 1,930 fourth-graders) were available for this study; 1,876 of
      the 3,270 children (57.4%) reportedly spent a significant amount of time
      unsupervised during the day. Unsupervised time that exceeded more than 2h per day
      increased the risk of delinquency, aggressive behaviors, and somatic complaints,
      as well as externalizing and internalizing problems. Carefully planned
      afterschool programming and care should be provided to children at high risk for
      inattention and problem behaviors. Also, a more comprehensive approach is needed
      to identify the possible mechanisms by which unsupervised time aggravates
      behavior problems in children predisposed for these behaviors. 

PMID- 24938743
TI  - Unique lamina propria stromal cells imprint the functional phenotype of mucosal
      dendritic cells.
AB  - Mucosal dendritic cells (DCs) in the intestine acquire the unique capacity to
      produce retinoic acid (RA), a vitamin A metabolite that induces gut tropism and
      regulates the functional differentiation of the T cells they prime. Here, we
      identified a stromal cell (SC) population in the intestinal lamina propria (LP),
      which is capable of inducing RA production in DCs in a RA- and granulocyte
      macrophage colony-stimulating factor (GM-CSF)-dependent fashion. Unlike DCs, LP
      SCs constitutively expressed the enzymatic machinery to produce RA even in the
      absence of dietary vitamin A, but were not able to do so in germ-free mice
      implying regulation by microbiota. Interestingly, DCs promoted GM-CSF production
      by the SCs indicating a two-way cross-talk between both cell types. Furthermore,
      RA-producing LP SCs and intestinal DCs localized closely in vivo suggesting that
      the interactions between both cell types might have an important role in the
      functional education of migratory DCs and therefore in the regulation of immune
      responses toward oral and commensal antigens. 

PMID- 24938744
TI  - Commensal Gram-positive bacteria initiates colitis by inducing
      monocyte/macrophage mobilization.
AB  - Breakdown of the intestinal epithelial layer's barrier function results in the
      inflow of commensal flora and improper immune responses against the commensal
      flora, leading to inflammatory bowel disease (IBD) development. Using a mouse
      dextran sodium sulfate (DSS)-induced colitis model, we show here that commensal
      Gram-positive bacteria trigger the mobilization of inflammatory monocytes and
      macrophages into the colon. Monocytes/macrophages are major producers of tumor
      necrosis factor-alpha (TNF-alpha), a representative cytokine that aggravates
      colitis. Notably, pretreating mice with vancomycin, which eliminated Gram
      positive bacteria, particularly the Lachnospiraceae family, significantly reduced
      the severity of the colitis by selectively blocking the recruitment of
      monocytes/macrophages, but not of other cells. Importantly, vancomycin treatment
      specifically downregulated the colonic epithelial cell (cEC) expression of C-C
      chemokine receptor type-2 (CCR2) ligands, which are critical chemokines for
      monocyte/macrophage mobilization into the inflamed colon. Collectively, these
      results provide previously undiscovered evidence that Gram-positive commensal
      bacteria induce colitis by recruiting colitogenic monocytes and macrophages. Our
      findings may lead to new avenues of treatment for IBD. 

PMID- 24938746
TI  - CD43-, but not CD43+, IL-10-producing CD1dhiCD5+ B cells suppress type 1 immune
      responses during Chlamydia muridarum genital tract infection.
AB  - Regulatory B (Breg) cells are known to modulate immune responses through
      predominantly interleukin-10 (IL-10)-dependent mechanisms and can be
      hypothetically divided into innate and adaptive subsets based on the nature of
      their activating signals. However, the specific role of different Breg subsets in
      modulating immune responses remains ambiguous. Here we have shown that Chlamydia
      induces IL-10-producing splenic B-cell populations consisting of CD43(+) and
      CD43(-) subsets of IgM(hi)IgD(lo) innate-like B (ILB) cells in vitro. While
      CD43(+)IL-10-producing B cells displayed innate type features and were readily
      induced by Chlamydia via Toll-like-receptor (TLR) signaling, CD43(-)IL-10
      producing B cells required additional B-cell activating factor (BAFF)-mediated
      signals from dendritic cells (DCs) for their differentiation and activation,
      thereby classifying them as adaptive type Bregs. Importantly, CD43(-), but not
      CD43(+), IL-10-producing ILB cells displayed bona fide Breg activity by potently
      suppressing interferon-gamma (IFN-gamma) production in vitro in an IL-10
      dependent manner. Furthermore, a novel CD43(-)CD1d(hi)CD5(+) IL-10-producing Breg
      population was predominantly induced by Chlamydia genital infection in vivo.
      Correspondingly, mixed bone marrow chimeric mice with B-cell-specific IL-10
      deficiency exhibited significantly increased type 1 immune responses, decreased
      bacterial burden, and reduced oviduct pathology upon infection. Our data
      demonstrate for the first time a distinct role for CD43(-)CD1d(hi)CD5(+)-adaptive
      Bregs over CD43(+) innate counterparts in controlling mucosal responses against
      intracellular bacterial infection. 

PMID- 24938747
TI  - Response to "CD8 subunit expression by plasmacytoid dendritic cells is variable,
      and does not define stable subsets".

PMID- 24938748
TI  - Identification of intestinal wall abnormalities and ischemia by modeling spatial
      uncertainty in computed tomography imaging findings.
AB  - Intestinal abnormalities and ischemia are medical conditions in which
      inflammation and injury of the intestine are caused by inadequate blood supply.
      Acute ischemia of the small bowel can be life-threatening. Computed tomography
      (CT) is currently a gold standard for the diagnosis of acute intestinal ischemia
      in the emergency department. However, the assessment of the diagnostic
      performance of CT findings in the detection of intestinal abnormalities and
      ischemia has been a difficult task for both radiologists and surgeons. Little
      effort has been found in developing computerized systems for the automated
      identification of these types of complex gastrointestinal disorders. In this
      paper, a geostatistical mapping of spatial uncertainty in CT scans is introduced
      for medical image feature extraction, which can be effectively applied for
      diagnostic detection of intestinal abnormalities and ischemia from control
      patterns. Experimental results obtained from the analysis of clinical data
      suggest the usefulness of the proposed uncertainty mapping model. 

PMID- 24938749
TI  - FGAP: an automated gap closing tool.
AB  - BACKGROUND: The fast reduction of prices of DNA sequencing allowed rapid
      accumulation of genome data. However, the process of obtaining complete genome
      sequences is still very time consuming and labor demanding. In addition, data
      produced from various sequencing technologies or alternative assemblies remain
      underexplored to improve assembly of incomplete genome sequences. FINDINGS: We
      have developed FGAP, a tool for closing gaps of draft genome sequences that takes
      advantage of different datasets. FGAP uses BLAST to align multiple contigs
      against a draft genome assembly aiming to find sequences that overlap gaps. The
      algorithm selects the best sequence to fill and eliminate the gap. CONCLUSIONS:
      FGAP reduced the number of gaps by 78% in an E. coli draft genome assembly using
      two different sequencing technologies, Illumina and 454. Using PacBio long reads,
      98% of gaps were solved. In human chromosome 14 assemblies, FGAP reduced the
      number of gaps by 35%. All the inserted sequences were validated with a reference
      genome using QUAST. The source code and a web tool are available at
      http://www.bioinfo.ufpr.br/fgap/.

PMID- 24938750
TI  - Immunoglobulins: expanding the role for mass spectrometry in protein biomarker
      quantification.

PMID- 24938751
TI  - Performance of hemoglobin A1c assay methods: good enough?

PMID- 24938752
TI  - Validation of a real-time PCR-based qualitative assay for the detection of
      methylated SEPT9 DNA in human plasma.
AB  - BACKGROUND: Epi proColon(r) is a new blood-based colorectal cancer (CRC)
      screening test designed to determine the methylation status of a promoter region
      of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe
      the analytical and clinical performance of the test. METHODS: Analytical
      performance at 4 testing laboratories included determination of limit of
      detection, precision, and reproducibility of the SEPT9 test. Clinical performance
      was evaluated in a prospective study by use of samples (n = 1544) from subjects
      enrolled in the PRESEPT clinical trial. Results were analyzed by comparison with
      colonoscopy, the reference standard. RESULTS: The limit of detection for
      methylated SEPT9 DNA was 7.8 pg/mL (95% CI 6-11 pg/mL) corresponding to <2 genome
      copies of methylated SEPT9 per milliliter of plasma. In the prospective clinical
      trial, sensitivity for all stages of CRC was 68% (95% CI 53%-80%) and for stage I
      III CRC, 64% (48%-77%). Adjusted specificity, on the basis of negative
      colonoscopy findings, was 80.0% (78%-82%). SIGNIFICANCE: The Epi proColon test is
      a simple, real-time PCR-based assay for the detection of methylated SEPT9 DNA in
      blood that may provide a noninvasive CRC screening alternative for people
      noncompliant with current CRC screening guidelines.

PMID- 24938754
TI  - Influence of the side-chain length on the cellular uptake and the cytotoxicity of
      rhenium triscarbonyl derivatives: a bimodal infrared and luminescence
      quantitative study.
AB  - Rhenium triscarbonyl complexes fac-[Re(CO)3 (N^N)] with appropriate ancillary N^N
      ligands are relevant for fluorescent bio-imaging. Recently, we have shown that
      [Re(CO)3 ] cores can also be efficiently mapped inside cells using their IR
      signature and that they can thus be used in a bimodal approach. To describe them
      we have coined the term SCoMPIs for single-core multimodal probes for imaging. In
      the context of the use of these SCoMPIs in bio-imaging, the questions of their
      cellular uptake and cytotoxicity are critical. We report here a series of
      compounds derived from the [Re(CO)3 Cl(pyta)] core (pyta=4-(2-pyridyl)-1,2,3
      triazole). The pyta ligand is of interest because it can be easily
      functionalized. Aliphatic side chains (C4 , C8 , and C12 ) were appended to this
      core. A correlative study involving IR and luminescence was performed to monitor
      and quantify their cellular internalization. We studied the relationship between
      lipophilicity (log P(o/w)), cytotoxicity (IC50 ), and cellular uptake, and we
      showed that both uptake and cytotoxicity increase with the length of the side
      chain, with a higher uptake for the C12 derivative. This study stresses the
      distinction that has to be made between apparent toxicity, determined as an
      incubation concentration IC50 , and intrinsic toxicity. Indeed, the intrinsic
      toxicity of a compound can remain hidden if it is not cell permeable. Therefore
      it must be kept in mind that IC50 values are composite values, reflecting both
      cellular uptake and intrinsic toxicity. 

PMID- 24938753
TI  - Speciation in Western Scrub-Jays, Haldane's rule, and genetic clines in secondary
      contact.
AB  - BACKGROUND: Haldane's Rule, the tendency for the heterogametic sex to show
      reduced fertility in hybrid crosses, can obscure the signal of gene flow in mtDNA
      between species where females are heterogametic. Therefore, it is important when
      studying speciation and species limits in female-heterogametic species like birds
      to assess the signature of gene flow in the nuclear genome as well. We studied
      introgression of microsatellites and mtDNA across a secondary contact zone
      between coastal and interior lineages of Western Scrub-Jays (Aphelocoma
      californica) to test for a signature of Haldane's Rule: a narrower cline of
      introgression in mtDNA compared to nuclear markers. RESULTS: Our initial
      phylogeographic analysis revealed that there is only one major area of contact
      between coastal and interior lineages and identified five genetic clusters with
      strong spatial structuring: Pacific Slope, Interior US, Edwards Plateau (Texas),
      Northern Mexico, and Southern Mexico. Consistent with predictions from Haldane's
      Rule, mtDNA showed a narrower cline than nuclear markers across a transect
      through the hybrid zone. This result is not being driven by female-biased
      dispersal because neutral diffusion analysis, which included estimates of sex
      specific dispersal rates, also showed less diffusion of mtDNA. Lineage-specific
      plumage traits were associated with nuclear genetic profiles for individuals in
      the hybrid zone, indicating that these differences are under genetic control.
      CONCLUSIONS: This study adds to a growing list of studies that support
      predictions of Haldane's Rule using cline analysis of multiple loci of differing
      inheritance modes, although alternate hypotheses like selection on different
      mtDNA types cannot be ruled out. That Haldane's Rule appears to be operating in
      this system suggests a measure of reproductive isolation between the Pacific
      Slope and interior lineages. Based on a variety of evidence from the phenotype,
      ecology, and genetics, we recommend elevating three lineages to species level: A.
      californica (Pacific Slope); A. woodhouseii (Interior US plus Edwards Plateau
      plus Northern Mexico); A. sumichrasti (Southern Mexico). The distinctive Edwards
      Plateau population in Texas, which was monophyletic in mtDNA except for one
      individual, should be studied in greater detail given habitat threat.

PMID- 24938755
TI  - Endothelium-dependent vasorelaxant effect of Alchemilla vulgaris methanol
      extract: a comparison with the aqueous extract in rat aorta.
AB  - We aimed to investigate the vascular effects of methanol extract (ME) and aqueous
      extract (AE) of Alchemilla vulgaris (Rosaceaea). Increasing concentrations of the
      ME (0.01-10 mg/mL) produced relaxations in noradrenaline (NA: 10-6 M) and K+ (40
      mM) precontracted aortas while contractions were obtained with the AE (0.01-10
      mg/mL). Responses to the ME were inhibited in the presence of putative inhibitors
      of endothelial vasodilators or after removal of the endothelium. Pretreatment of
      aortic rings with the ME (10 mg/mL, 20 min) reduced the maximal contractions to
      NA and K+, whereas an enhanced contractility was observed with the AE (10 mg/mL,
      20 min). Total flavonoid content was higher in the ME than in the AE. Quercetin
      was determined particularly high in the ME while gallic acid was high in the AE.
      Our results indicated that the ME of A. vulgaris displays favourable vascular
      effects via endothelium-dependent mechanisms.

PMID- 24938756
TI  - Laser light triggers increased Raman amplification in the regime of nonlinear
      Landau damping.
AB  - Stimulated Raman backscattering (SRS) has many unwanted effects in megajoule
      scale inertially confined fusion (ICF) plasmas. Moreover, attempts to harness SRS
      to amplify short laser pulses through backward Raman amplification have achieved
      limited success. In high-temperature fusion plasmas, SRS usually occurs in a
      kinetic regime where the nonlinear response of the Langmuir wave to the laser
      drive and its host of complicating factors make it difficult to predict the
      degree of amplification that can be achieved under given experimental conditions.
      Here we present experimental evidence of reduced Landau damping with increasing
      Langmuir wave amplitude and determine its effects on Raman amplification. The
      threshold for trapping effects to influence the amplification is shown to be very
      low. Above threshold, the complex SRS dynamics results in increased amplification
      factors, which partly explains previous ICF experiments. These insights could aid
      the development of more efficient backward Raman amplification schemes in this
      regime. 

PMID- 24938757
TI  - CT based three dimensional dose-volume evaluations for high-dose rate
      intracavitary brachytherapy for cervical cancer.
AB  - BACKGROUND: In this study, high risk clinical target volumes (HR-CTVs) according
      to GEC-ESTRO guideline were contoured retrospectively based on CT images taken at
      the time of high-dose rate intracavitary brachytherapy (HDR-ICBT) and correlation
      between clinical outcome and dose of HR-CTV were analyzed. METHODS: Our study
      population consists of 51 patients with cervical cancer (Stages IB-IVA) treated
      with 50 Gy external beam radiotherapy (EBRT) using central shield combined with 2
      5 times of 6 Gy HDR-ICBT with or without weekly cisplatin. Dose calculation was
      based on Manchester system and prescribed dose of 6 Gy were delivered for point
      A. CT images taken at the time of each HDR-ICBT were reviewed and HR-CTVs were
      contoured. Doses were converted to the equivalent dose in 2 Gy (EQD2) by applying
      the linear quadratic model (alpha/beta = 10 Gy). RESULTS: Three-year overall
      survival, Progression-free survival, and local control rate was 82.4%, 85.3% and
      91.7%, respectively. Median cumulative dose of HR-CTV D90 was 65.0 Gy (52.7-101.7
      Gy). Median length from tandem to the most lateral edge of HR-CTV at the first
      ICBT was 29.2 mm (range, 18.0-51.9 mm). On univariate analysis, both LCR and PFS
      was significantly favorable in those patients D90 for HR-CTV was 60 Gy or greater
      (p = 0.001 and 0.03, respectively). PFS was significantly favorable in those
      patients maximum length from tandem to edge of HR-CTV at first ICBT was shorter
      than 3.5 cm (p = 0.042). CONCLUSION: Volume-dose showed a relationship to the
      clinical outcome in CT based brachytherapy for cervical carcinoma.

PMID- 24938758
TI  - A comprehensive neuropsychological description of cognition in drug-refractory
      juvenile myoclonic epilepsy.
AB  - The study of juvenile myoclonic epilepsy is important in that: it is common and
      heterogeneous; the etiology is unknown; and patients report broad cognitive
      problems. We utilized a broad battery of neuropsychometric tests to assess the
      following: intellectual function, memory, language and naming, executive
      function, the impact of epilepsy, and antiepilepsy drug side effects. Sixty
      people with drug-refractory JME were interviewed, and performance was profoundly
      impaired across the range of tests. Impairments included the following: full
      scale IQ (89, p<0.001); processing speed (86, p<0.001); visual memory (immediate
      and delayed) more affected than verbal memory; verbal fluency and inhibition
      (p<0.001); and self-reported drug side effects (p<0.001). Eighty-three percent of
      patients exhibited frank executive dysfunction, which was moderate to severe in
      66%. Regression modeling confirmed that an early age at onset and the need for
      polytherapy were associated with poorer cognitive outcomes. This study confirms
      previous reports of executive dysfunction in a larger cohort and with greater
      statistical rigor. We also identified a high prevalence of neurotoxicity symptoms
      such as fatigue and poorer functioning across intellectual and memory tests than
      had previously been reported. 

PMID- 24938759
TI  - Experimental treatment of Curvularia infection.
AB  - We have evaluated the efficacy of amphotericin B, posaconazole, and voriconazole
      in immunosuppressed murine models of disseminated infection by Curvularia
      spicifera and Curvularia hawaiiensis. The 3 antifungals improved survival of mice
      in comparison to controls; however, only the 2 azoles were able to reduce
      significantly the fungal load. 

PMID- 24938760
TI  - Rapid urine antigen testing for Streptococcus pneumoniae in adults with community
      acquired pneumonia: clinical use and barriers.
AB  - Streptococcus pneumoniae (pneumococcus) is the most common bacterial etiology of
      community-acquired pneumonia (CAP) in adults, a leading cause of death. The
      majority of pneumococcal CAP is diagnosed by blood culture, which likely
      underestimates the burden of disease. The 2007 CAP guidelines recommend routine
      use of the rapid pneumococcal urinary antigen (UAg) test. To assess the how
      pneumococcal UAg testing is being used among hospitalized adult CAP patients and
      what barriers restrict its use, a Web-based survey was distributed in 2013 to
      1287 infectious disease physician members of the Emerging Infectious disease
      Network of the Infectious Disease Society of America. Of 493 eligible responses,
      65% use the pneumococcal UAg test. The primary barrier to UAg use was
      availability (46%). UAg users reported ordering fewer other diagnostic tests and
      tailoring antibiotic therapy. Increased access to UAg tests could improve
      pneumonia management and pneumococcal CAP surveillance. 

PMID- 24938761
TI  - Why patients may not exercise their choice when referred for hospital care. An
      exploratory study based on interviews with patients.
AB  - BACKGROUND: Various north-western European health-care systems encourage patients
      to make an active choice of health-care provider. This study explores,
      qualitatively, patients' hospital selection processes and provides insight into
      the reasons why patients do or do not make active choices. METHODS: Semi
      structured individual interviews were conducted with 142 patients in two
      departments of three Dutch hospitals. Interviews were recorded, transcribed and
      analysed in accordance with the grounded theory approach. RESULTS: Three levels
      of choice activation were identified - passive, semi-active and active. The
      majority of the patients, however, visited the default hospital without having
      used quality information or considered alternatives. Various factors relating to
      patient, provider and health-care system characteristics were identified that
      influenced patients' level of choice activation. On the whole, the patients
      interviewed could be classified into five types with regard to how they chose, or
      'ended up at' a hospital. These types varied from patients who did not have a
      choice to patients who made an active choice. CONCLUSIONS: A large variation
      exists in the way patients choose a hospital. However, most patients tend to
      visit the default without being concerned about choice. Generally, they do not
      see any reason to choose another hospital. In addition, barriers exist to making
      choices. The idea of a patient who actively makes a choice originates from
      neoclassical microeconomic theory. However, policy makers may try in vain to
      bring principles originating from this theory into health care. Even so, patients
      do value the opportunity of attending 'their' own hospital.

PMID- 24938762
TI  - Analysis of RBFOX1 gene expression in lymphoblastoid cell lines of Italian
      discordant autism spectrum disorders sib-pairs.
AB  - Several lines of evidence suggest that RBFOX1 is a key regulator of
      transcriptional and splicing programs in neural cells during development, and
      that it is expressed in a neuronal module enriched for known autism
      susceptibility genes. We have investigated its expression by semiquantitative RT
      PCR in accessible nonbrain resources in eighteen autism spectrum disorder sib
      pairs belonging to the Italian Autism Network cohort. RBFOX1 gene expression was
      detected in lymphoblastoid cell lines but not in lymphocytes. No significant
      differences between autism spectrum disorders and non-affected brothers were
      found. We were not able to replicate in lymphoblastoid cell lines the previously
      reported RBFOX1 gene downregulation in autism, even if a trend was observed. This
      might be due to less pronounced transcription level differences in RBFOX1 gene
      expression in lymphoblastoid cell lines than in brain samples. 

PMID- 24938763
TI  - Determination and stereochemistry of proteinogenic and non-proteinogenic amino
      acids in Saudi Arabian date fruits.
AB  - Whereas an abundance of literature is available on the occurrence of common
      proteinogenic amino acids (AAs) in edible fruits of the date palm (Phoenix
      dactylifera L.), recent reports on non-proteinogenic (non-coded) AAs and amino
      components are scarce. With emphasis on these components we have analyzed total
      hydrolysates of twelve cultivars of date fruits using automated ion-exchange
      chromatography, HPLC employing a fluorescent aminoquinolyl label, and GC-MS of
      total hydrolysates using the chiral stationary phases Chirasil((r))-L-Val and
      Lipodex((r)) E. Besides common proteinogenic AAs, relatively large amounts of the
      following non-proteinogenic amino acids were detected: (2S,5R)-5-hydroxypipecolic
      acid (1.4-4.0 g/kg dry matter, DM), 1-aminocyclopropane-1-carboxylic acid (1.3
      2.6 g/kg DM), gamma-amino-n-butyric acid (0.5-1.2 g/kg DM), (2S,4R)-4
      hydroxyproline (130-230 mg/kg DM), L-pipecolic acid (40-140 mg/kg DM), and 2
      aminoethanol (40-160 mg/kg DM) as well as low or trace amounts (<70 mg/kg DM) of
      L-ornithine, 5-hydroxylysine, beta-alanine, and in some samples (<20 mg/kg DM) of
      (S)-beta-aminoisobutyric acid and (<10 mg/kg DM) L-allo-isoleucine. In one date
      fruit, traces of alpha-aminoadipic acid could be determined. Enantiomeric
      analysis of 6 M DCl/D2O hydrolysates of AAs using chiral capillary gas
      chromatography-mass spectrometry revealed the presence of very low amounts of D
      Ala, D-Asp, D-Glu, D-Ser and D-Phe (1.2-0.4%, relative to the corresponding L
      enantiomers), besides traces (0.2-1%) of other D-AAs. The possible relevance of
      non-proteinogenic amino acids in date fruits is briefly addressed.

PMID- 24938764
TI  - Increased dietary vitamin D suppresses MAPK signaling, colitis, and colon cancer.
AB  - Epidemiologic studies associate low serum vitamin D levels with an increased risk
      of colon cancer and inflammatory diseases such as inflammatory bowel disease
      (IBD). 129-Smad3(tm1Par)/J (Smad3(-/-)) mice are a model of bacteria-driven
      colitis and colon cancer when infected with Helicobacter bilis (H. bilis). Thus,
      we used this mouse model to determine whether increased dietary vitamin D would
      reduce inflammation and colon cancer. Smad3(-/-) mice were fed purified diet with
      either maintenance (1 IU vitamin D/g diet; maintenance) or increased
      concentrations of vitamin D (5 IU vitamin D/g diet; high vitamin D). One week
      after diet initiation, mice were inoculated with broth or H. bilis and were
      necropsied at several time points postinoculation to assess inflammation,
      dysplasia, and neoplasia incidence. At 16 weeks postinfection, 11% of mice fed
      high vitamin D diet had cancer compared with 41% of mice fed maintenance diet (P
      = 0.0121). Evaluation at an early time point (1 week postinfection) showed that
      animals fed high vitamin D had decreased MAPK (p-P38 and p-JNK) activation in
      lamina propria leukocytes as well as decreased NFkappaB activation in colonic
      epithelial cells. Reduction in MAPK and NFkappaB activation correlated with
      decreased IBD scores (2.7 vs. 15.5; P < 0.0001) as well as decreased inflammatory
      cell infiltrates and reduced expression of proinflammatory cytokines in cecal
      tissue. These findings suggest that increased dietary vitamin D is beneficial in
      preventing inflammation-associated colon cancer through suppression of
      inflammatory responses during initiation of neoplasia or early-stage
      carcinogenesis.

PMID- 24938765
TI  - Engineered fusokine GIFT4 licenses the ability of B cells to trigger a
      tumoricidal T-cell response.
AB  - Engineered chimeric cytokines can generate gain-of-function activity in immune
      cells. Here, we report potent antitumor activity for a novel fusion cytokine
      generated by N-terminal coupling of GM-CSF to IL4, generating a fusokine termed
      GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL4 receptors on the cell
      surface and displayed a pan-STAT hyperphosphorylation associated with acquisition
      of a distinct phenotype and function described to date. In C57BL/6J mice,
      administration of GIFT4 expanded endogenous B cells and suppressed the growth of
      B16F0 melanoma cells. Furthermore, B16F0 melanoma cells engineered to secrete
      GIFT4 were rejected immunologically in a B-cell-dependent manner. This effect was
      abolished when GIFT4-expressing B16F0 cells were implanted in B-cell-deficient
      mice, confirming a B-cell-dependent antitumor effect. Human GIFT4-licensed B
      cells primed cytotoxic T cells and specifically killed melanoma cells in vitro
      and in vivo. Taken together, our results demonstrated that GIFT4 could mediate
      expansion of B cells with potent antigen-specific effector function. GIFT4 may
      offer a novel immunotherapeutic tool and define a previously unrecognized
      potential for B cells in melanoma immunotherapy.

PMID- 24938767
TI  - Mutations in Ralstonia solanacearum loci involved in lipopolysaccharide
      biogenesis, phospholipid trafficking and peptidoglycan recycling render
      bacteriophage infection.
AB  - Ralstonia solanacearum causes deadly wilting on many crops worldwide. However,
      the information on its components important for cell integrity and interactions
      with phages is limited. By systematically characterizing mutants resistant to a
      T7-like phage, we showed that the biosynthesis of rough lipopolysaccharides (R
      LPS) was crucial for maintaining the membrane integrity, while the production of
      smooth LPS (S-LPS) was required for the resistance to polymyxin B and phage
      adsorption. Furthermore, RSc0154/ampG disruption did not affect LPS production
      and phage adsorption but may have caused aberrant release of peptidoglycan
      fragments, thus hindering phage DNA injection into or virion release from the
      cell. Mutations in the RSc2958-RSc2962/mla cluster, although not affecting LPS
      production, may have caused elevated phospholipid level in the outer leaflet of
      the outer membrane, consequently sheltering the mutants from phage adsorption on
      the O-antigen. These results specify important roles of the biogenesis and
      homeogenesis of envelope components for R. solanacearum-phage interaction. 

PMID- 24938766
TI  - B-cell expansion and lymphomagenesis induced by chronic CD40 signaling is
      strictly dependent on CD19.
AB  - CD40, a member of the TNF receptor family, is expressed on all mature B cells and
      on most B-cell lymphomas. Recently, we have shown that constitutive activation of
      CD40 signaling in B cells induced by a fusion protein consisting of the
      transmembrane part of the Epstein-Barr viral latent membrane protein 1 (LMP1) and
      the cytoplasmic part of CD40 (LMP1/CD40) drives B-cell lymphoma development in
      transgenic mice. Because LMP1/CD40-expressing B cells showed an upregulation of
      CD19, we investigated CD19's function in CD40-driven B-cell expansion and
      lymphomagenesis. Here, we demonstrate that ablation of CD19 in LMP1/CD40
      transgenic mice resulted in a severe loss and reduced lifespan of mature B cells
      and completely abrogated development of B-cell lymphoma. CD19 is localized to
      lipid rafts and constitutively activated by the LMP1/CD40 fusion protein in B
      cells. We provide evidence that the improved survival and malignant
      transformation of LMP1/CD40-expressing B cells are dependent on activation of the
      MAPK Erk that is mediated through CD19 in a PI3K-dependent manner. Our data
      suggest that constitutively active CD40 is dependent on CD19 to transmit survival
      and proliferation signals. Moreover, we detected a similarly functioning
      prosurvival pathway involving phosphorylated CD19 and PI3K-dependent Erk
      phosphorylation in human diffuse large B-cell lymphoma cell lines. Our data
      provide evidence that CD19 plays an important role in transmitting survival and
      proliferation signals downstream of CD40 and therefore might be an interesting
      therapeutic target for the treatment of lymphoma undergoing chronic CD40
      signaling.

PMID- 24938768
TI  - Rhizobial infection in Adesmia bicolor (Fabaceae) roots.
AB  - The native legume Adesmia bicolor shows nitrogen fixation efficiency via
      symbiosis with soil rhizobia. The infection mechanism by means of which rhizobia
      infect their roots has not been fully elucidated to date. Therefore, the purpose
      of the present study was to identify the infection mechanism in Adesmia bicolor
      roots. To this end, inoculated roots were processed following conventional
      methods as part of our root anatomy study, and the shape and distribution of root
      nodules were analyzed as well. Neither root hairs nor infection threads were
      observed in the root system, whereas infection sites-later forming nodules-were
      observed in the longitudinal sections. Nodules were found to form between the
      main root and the lateral roots. It can be concluded that in Adesmia bicolor, a
      bacterial crack entry infection mechanism prevails and that such mechanism could
      be an adaptive strategy of this species which is typical of arid environments. 

PMID- 24938769
TI  - Case management for frequent users of the emergency department: study protocol of
      a randomised controlled trial.
AB  - BACKGROUND: We devised a randomised controlled trial to evaluate the
      effectiveness and efficiency of an intervention based on case management care for
      frequent emergency department users. The aim of the intervention is to reduce
      such patients' emergency department use, to improve their quality of life, and to
      reduce costs consequent on frequent use. The intervention consists of a
      combination of comprehensive case management care and standard emergency care. It
      uses a clinical case management model that is patient-identified, patient
      directed, and developed to provide high intensity services. It provides a
      continuum of hospital- and community-based patient services, which include
      clinical assessment, outreach referral, and coordination and communication with
      other service providers. METHODS/DESIGN: We aim to recruit, during the first year
      of the study, 250 patients who visit the emergency department of the University
      Hospital of Lausanne, Switzerland. Eligible patients will have visited the
      emergency department 5 or more times during the previous 12 months. Randomisation
      of the participants to the intervention or control groups will be computer
      generated and concealed. The statistician and each patient will be blinded to the
      patient's allocation. Participants in the intervention group (N = 125),
      additionally to standard emergency care, will receive case management from a
      team, 1 (ambulatory care) to 3 (hospitalization) times during their stay and
      after 1, 3, and 5 months, at their residence, in the hospital or in the
      ambulatory care setting. In between the consultations provided, the patients will
      have the opportunity to contact, at any moment, the case management team.
      Participants in the control group (N = 125) will receive standard emergency care
      only. Data will be collected at baseline and 2, 5.5, 9, and 12 months later,
      including: number of emergency department visits, quality of life (EuroQOL and
      WHOQOL), health services use, and relevant costs. Data on feelings of
      discrimination and patient's satisfaction will also be collected at the baseline
      and 12 months later. DISCUSSION: Our study will help to clarify knowledge gaps
      regarding the positive outcomes (emergency department visits, quality of life,
      efficiency, and cost-utility) of an intervention based on case management care.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01934322.

PMID- 24938771
TI  - Changing the role of the traditional birth attendant in Somaliland.
AB  - OBJECTIVE: To explore the feasibility of changing the role of the traditional
      birth attendant (TBA) to act as birth companion and promoter of skilled birth
      attendance. METHODS: Between 2008 and 2012, 75 TBAs received 3days of training
      and were paid US $5 for each patient brought to any of five healthcare facilities
      in Maroodi Jeex, Somaliland. Health facilities were upgraded (infrastructure,
      drugs and equipment, staff training, and incentivization). Eight key informant
      interviews (KIIs) and 10 focus group discussions (FGDs) involving 32 TBAs and 32
      mothers were conducted. A framework approach was used for analysis. RESULTS: TBAs
      adopted their new role easily; instead of conducting home births and referring
      women to a facility only at onset of complications, they accompanied or referred
      mothers to a nearby facility for delivery, prenatal care, or postnatal care. Both
      TBAs and mothers accepted this new role, resulting in increased deliveries at
      health facilities. Facilitating factors included the creation of an enabling
      environment at the health facility, acceptance of the TBA by health facility
      staff, and monetary incentivization. CONCLUSION: Changing the role of the TBA to
      support facility-based delivery is feasible and acceptable. Further research is
      needed to see whether this is replicable and can be scaled-up.

PMID- 24938770
TI  - The immediate effects of fitting and tuning solid ankle-foot orthoses in early
      stroke rehabilitation.
AB  - BACKGROUND: Ankle-foot orthoses are known to have a generally positive effect on
      gait in stroke, however the specifc type of AFO and the time point at which it is
      provided are highly variable in the currently available literature. OBJECTIVE:
      The objective was to determine the immediate spatiotemporal and kinematic effect
      of custom-made solid ankle-foot orthoses in early stroke rehabilitation, compared
      to shod walking. METHODS: Five male and three female participants were recruited
      to the study (n = 8), with a mean age of 57 (16) years who were 3.5 (3) weeks
      post-stroke. Each received a custom-made solid ankle-foot orthosis to a
      predefined set of design criteria and tuned using heel wedges to control the
      shank inclination angle during shod walking. Repeated spatiotemporal and three
      dimensional gait measures were taken pre- and immediately post-intervention.
      STUDY DESIGN: A pre-post-test experimental study. RESULTS: With the solid ankle
      foot orthosis, walking velocity increased from 0.22 (0.2) to 0.36 (0.3) m/s (p <
      0.05), overall average step length increased from 0.28 (0.1) to 0.37 (0.1) m (p <
      0.05), cadence increased from 45 (19) to 56 (19) steps/min (p < 0.05) and step
      length symmetry ratio increased from 0.65 (0.2) to 0.74 (0.2) (not significant).
      No clear changes were observed in the joint kinematics of the hip and knee.
      CONCLUSION: In our small group of early stroke patients who were fitted with a
      solid ankle-foot orthosis, immediate significant improvements occurred in walking
      speed, step length and cadence, when compared to walking with shoes only.
      CLINICAL RELEVANCE: This study provides evidence about the immediate effects of
      custom solid ankle-foot orthoses on gait of early stroke survivors. Ankle-foot
      orthosis design specifications are fully described for replication. This study
      suggests that observing global segment orientation may be more useful than joint
      angles when fitting and tuning ankle-foot orthoses for optimal ankle-foot
      orthosis/footwear alignment.

PMID- 24938772
TI  - Looking at the kidney to predict global outcome in the elderly.

PMID- 24938773
TI  - Inhibition of brain ischemia-caused notch activation in microglia may contribute
      to isoflurane postconditioning-induced neuroprotection in male rats.
AB  - Prolonged exposure to volatile anesthetics alone may be detrimental to the brain.
      However, volatile anesthetics, such as isoflurane, can provide neuroprotection
      against various damaging insults. Application of isoflurane after focal brain
      ischemia reduces ischemic brain injury. We determined whether this isoflurane
      postconditioning-induced neuroprotection requires inhibition of brain ischemia
      induced Notch signaling activation. Here, we showed that TUNEL-positive staining
      cell density and active caspase 3 expression were increased in the ischemic
      penumbral brain tissues of male rats after a 90-min middle cerebral arterial
      occlusion (MCAO). This increase was inhibited by isoflurane postconditioning and
      a Notch inhibitor. Isoflurane postconditioning and the Notch inhibitor also
      inhibited brain ischemia-induced Notch activation and proinflammatory cytokine
      production. Most cells expressing active Notch also were positive for CD11b, a
      microglial and white blood cell marker. Isoflurane postconditioning and the Notch
      inhibitor inhibited 1 ng/ml lipopolysaccharide- and oxygen-glucose deprivation
      induced Notch activation and proinflammatory cytokine production from microglial
      cultures. The inhibition of cytokine production by isoflurane postconditioning,
      but not by a high concentration of the Notch inhibitor, disappeared in the
      presence of 10 ng/ml lipopolysaccharide. Our results suggest that Notch
      activation in microglia contributes to the cell apoptosis in the ischemic brain
      tissues. Inhibiting this Notch activation may participate in isoflurane
      postconditioning-induced neuroprotection against transient focal brain ischemia
      in male rats.

PMID- 24938775
TI  - Effect of glatiramer acetate on peripheral blood brain-derived neurotrophic
      factor and phosphorylated TrkB levels in relapsing-remitting multiple sclerosis.
AB  - Glatiramer acetate (GA) is one of the most widely used disease-modifying drugs
      for the treatment of relapsing-remitting multiple sclerosis; is assumed to have
      inductor effects on neurotrophic factor expression. One of these neurotrophic
      factor systems is the brain-derived neurotrophic factor (BDNF)/receptor tyrosine
      kinase B (TrkB) pathway. Peripheral blood is thought to contain soluble BDNF, and
      some blood cells express TrkB. We attempted to determine whether GA treatment
      leads to changes in plasma BDNF levels and TrkB activation. Such a phenomenon are
      relapsing-remitting multiple sclerosis patients is significantly reduced; GA
      treatment is not influencing peripheral BDNF levels, after one year of sustained
      therapy, not from the point of view of total free BDNF nor the phosphorylated
      TrkB.

PMID- 24938776
TI  - Scopolamine and depression: a role for muscarinic antagonism?
AB  - Depressive disorders have, for a sizeable extent, proven resilient to
      pharmacotherapy. Established drugs such as selective serotonin reuptake
      inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs) often
      provide inadequate symptom relief and sometimes fail altogether. Recently,
      interest in antidepressant effects of scopolamine, a non-selective muscarinic
      acetylcholine receptor (mAChR) antagonist, has arisen. Initial evidence suggests
      that scopolamine provides relatively rapid and long-lasting symptom alleviation
      for unipolar and bipolar depressed patients. At the same time, side effects of
      medical dosages appear mild and transient in nature. The aim of the present
      review is to tentatively discuss the antidepressant potential of scopolamine and
      to outline putative neurobiological pathways. Clearly, mAChR antagonism provides
      an intriguing novel therapeutical approach for treating depressive disorders.

PMID- 24938777
TI  - Neuroprotective effects of Citrus reticulata in scopolamine-induced dementia
      oxidative stress in rats.
AB  - The purpose of the study was to evaluate the potential effects of Citrus
      reticulate (mandarin) peel methanolic extract (MPME) on memory dysfunction in
      rats. Memory impairment was produced by scopolamine (1.4 mg/kg, intraperitoneally
      injected). Brain acetylcholinesterase enzyme (AChE) activity was measured to
      assess the central cholinergic activity. This study also investigated the effect
      of scopolamine on norepinephrine, dopamine and serotonin content in rat
      hippocampus, striatum and cerebral cortex. In addition, the levels of brain lipid
      peroxidation (LPO), nitric oxide (NO) and glutathione (GSH) were estimated to
      assess the degree of oxidative stress. Scopolamine administration induced a
      significant impairment of central cholinergic activity in rats, as indicated by a
      marked increase in AChE activity. The impairment of the cholinergic system was
      associated with a significant alternation in brain monoamines. Scopolamine
      administration also caused oxidant damage (elevation in LPO and NO and reduction
      in GSH levels). Pretreatment of MPME (250 mg/kg, orally administered)
      significantly reduced scopolamine-induced alternation in brain monoamines with an
      attenuation of scopolamine-induced rise in brain AChE activity and brain
      oxidative stress. It is concluded that administration of mandarin peel extract,
      demonstrating antioxidant activity, may be of value for dementia exhibiting
      elevated brain oxidative status.

PMID- 24938778
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma: Report of 2 Cases and
      Review of the Literature.
AB  - Although primary breast lymphomas are exceedingly rare, cases of breast implant
      associated anaplastic large cell lymphoma (iALCL) continue to be reported. The
      authors describe their experience with 2 patients and review the literature. Both
      patients presented with periprosthetic fluid collection. Neither had evidence of
      systemic disease nor received systemic therapy. Both were disease free after
      bilateral capsulectomies and implant removal without implant replacement, and
      disease did not recur. During the literature review, 63 cases of iALCL (including
      our 2 patients) were identified. The median time from implant placement to
      diagnosis was 9 years. Both saline and silicone implants were associated with
      iALCL. Of the 26 cases for which implant surface was reported, the surface was
      textured in 24. Of the 58 patients with an identifiable presentation, 39 had
      periprosthetic fluid collection, including 7 with an associated mass; 13 had an
      isolated mass at presentation, including 1 with axillary adenopathy. Forty
      patients had capsulectomy, 7 of whom underwent implant replacement. Of the 44
      patients with known treatment, 33 received chemotherapy and 23 received
      radiation. Of the 49 patients with known anaplastic large cell lymphoma, 15 had
      disease recurrence, and 4 patient deaths were reported. Of the 18 patients
      presenting with a mass, 11 had disease recurrence, including all 4 patients who
      died. This study represents the largest review of patients with iALCL described
      to date. Although most cases have an indolent clinical course, the variety of
      presentations defined as "seroma" vs "capsular involvement" emphasizes the
      importance of investigating a definitive method of diagnosis, management, and
      treatment of this disease. LEVEL OF EVIDENCE 5. 

PMID- 24938779
TI  - Catalytic conversion of gamma-valerolactone to epsilon-caprolactam: towards nylon
      from renewable feedstock.
AB  - The conversion of gamma-valerolactone (GVL) in three atom-efficient steps to the
      important polymer precursor epsilon-caprolactam is reported. The bio-based GVL
      can be converted to a mixture of isomeric methyl pentenoates (MP) via trans
      esterification with methanol with 94% yield (ratio of 3-MP/4-MP=3:1); subsequent
      aminolysis with ammonia leads to a mixture of pentenamides (PA) almost
      quantitatively (99% conversion). The resulting pentenamides are ultimately
      converted into epsilon-caprolactam via a rhodium-catalyzed intramolecular
      hydroamidomethylation reaction, comprising an initial hydroformylation of the
      alkene moiety of PA and subsequent ring-closing reductive amidation of the
      resulting aldehyde with the amide functionality. A promising yield of caprolactam
      of about 90% can be obtained with a Rh/xantphos catalyst system in a two-stage
      hydroformylation-reductive amidation using pure 4-PA as feedstock. The use of 3
      PA as a substrate not only results in a significantly lower regioselectivity for
      the 7-membered lactam, but also in the formation of high amounts of valeramide
      (VA). Consequently, a best overall yield of caprolactam of nearly 40% could be
      demonstrated with a Rh/POP-xantphos [POP-xantphos=4,5-bis(2,8-dimethyl-10
      phenoxaphosphino)-9,9,-dimethylxanthene] catalyst system based on the 3:1 mixture
      of 3-PA/4-PA directly obtainable from GVL.

PMID- 24938780
TI  - [Wiesner nevus: a new melanocytic tumor defined by molecular genetic analysis].

PMID- 24938781
TI  - Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber
      conversion and dilated cardiomyopathy.
AB  - Correct regulation of troponin and myosin contractile protein gene isoforms is a
      critical determinant of cardiac and skeletal striated muscle development and
      function, with misexpression frequently associated with impaired contractility or
      disease. Here we reveal a novel requirement for Prospero-related homeobox factor
      1 (Prox1) during mouse heart development in the direct transcriptional repression
      of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin
      light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive
      beyond birth with hearts characterized by marked overexpression of fast-twitch
      genes and postnatal development of a fatal dilated cardiomyopathy. Through
      conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved
      requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin
      light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1
      ablation as sufficient to cause a switch from a slow- to fast-twitch muscle
      phenotype. Our study identifies conserved roles for Prox1 between cardiac and
      skeletal muscle, specifically implicated in slow-twitch fiber-type specification,
      function, and cardiomyopathic disease. 

PMID- 24938784
TI  - Microbiomes are true to type.

PMID- 24938782
TI  - Differences in nucleation behavior underlie the contrasting aggregation kinetics
      of the Abeta40 and Abeta42 peptides.
AB  - The two major forms of the amyloid-beta (Abeta) peptide found in plaques in
      patients suffering from Alzheimer's disease, Abeta40 and Abeta42, only differ by
      two amino acids in the C-terminal region, yet they display markedly different
      aggregation behavior. The origins of these differences have remained challenging
      to connect to specific molecular-level processes underlying the aggregation
      reaction. In this paper we use a general strategy to apply the conventional
      workflow of chemical kinetics to the aggregation of the Abeta40 peptide to
      identify the differences between Abeta40 and Abeta42 in terms of the microscopic
      determinants of the aggregation reaction. Our results reveal that the major
      source of aggregates in the case of Abeta40 is a fibril-catalyzed nucleation
      process, the multistep nature of which is evident through its saturation
      behavior. Moreover, our results show that the significant differences in the
      observed behavior of the two proteins originate not simply from a uniform
      increase in all microscopic rates for Abeta42 compared with Abeta40, but rather
      are due to a shift of more than one order of magnitude in the relative importance
      of primary nucleation versus fibril-catalyzed secondary nucleation processes.
      This analysis sheds light on the microscopic determinants of the aggregation
      behavior of the principal forms of Abeta and outlines a general approach toward
      achieving an understanding at the molecular level of the aberrant deposition of
      insoluble peptides in neurodegenerative disorders. 

PMID- 24938783
TI  - Chemical cross-linking/mass spectrometry targeting acidic residues in proteins
      and protein complexes.
AB  - The study of proteins and protein complexes using chemical cross-linking followed
      by the MS identification of the cross-linked peptides has found increasingly
      widespread use in recent years. Thus far, such analyses have used almost
      exclusively homobifunctional, amine-reactive cross-linking reagents. Here we
      report the development and application of an orthogonal cross-linking chemistry
      specific for carboxyl groups. Chemical cross-linking of acidic residues is
      achieved using homobifunctional dihydrazides as cross-linking reagents and a
      coupling chemistry at neutral pH that is compatible with the structural integrity
      of most protein complexes. In addition to cross-links formed through insertion of
      the dihydrazides with different spacer lengths, zero-length cross-link products
      are also obtained, thereby providing additional structural information. We
      demonstrate the application of the reaction and the MS identification of the
      resulting cross-linked peptides for the chaperonin TRiC/CCT and the 26S
      proteasome. The results indicate that the targeting of acidic residues for cross
      linking provides distance restraints that are complementary and orthogonal to
      those obtained from lysine cross-linking, thereby expanding the yield of
      structural information that can be obtained from cross-linking studies and used
      in hybrid modeling approaches. 

PMID- 24938786
TI  - Origins of specificity and affinity in antibody-protein interactions.
AB  - Natural antibodies are frequently elicited to recognize diverse protein surfaces,
      where the sequence features of the epitopes are frequently indistinguishable from
      those of nonepitope protein surfaces. It is not clearly understood how the
      paratopes are able to recognize sequence-wise featureless epitopes and how a
      natural antibody repertoire with limited variants can recognize seemingly
      unlimited protein antigens foreign to the host immune system. In this work,
      computational methods were used to predict the functional paratopes with the 3D
      antibody variable domain structure as input. The predicted functional paratopes
      were reasonably validated by the hot spot residues known from experimental
      alanine scanning measurements. The functional paratope (hot spot) predictions on
      a set of 111 antibody-antigen complex structures indicate that aromatic, mostly
      tyrosyl, side chains constitute the major part of the predicted functional
      paratopes, with short-chain hydrophilic residues forming the minor portion of the
      predicted functional paratopes. These aromatic side chains interact mostly with
      the epitope main chain atoms and side-chain carbons. The functional paratopes are
      surrounded by favorable polar atomistic contacts in the structural paratope
      epitope interfaces; more that 80% these polar contacts are electrostatically
      favorable and about 40% of these polar contacts form direct hydrogen bonds across
      the interfaces. These results indicate that a limited repertoire of antibodies
      bearing paratopes with diverse structural contours enriched with aromatic side
      chains among short-chain hydrophilic residues can recognize all sorts of protein
      surfaces, because the determinants for antibody recognition are common
      physicochemical features ubiquitously distributed over all protein surfaces. 

PMID- 24938785
TI  - LptE binds to and alters the physical state of LPS to catalyze its assembly at
      the cell surface.
AB  - The assembly of lipopolysaccharide (LPS) on the surface of Gram-negative
      bacterial cells is essential for their viability and is achieved by the seven
      protein LPS transport (Lpt) pathway. The outer membrane (OM) lipoprotein LptE and
      the beta-barrel membrane protein LptD form a complex that assembles LPS into the
      outer leaflet of the OM. We report a crystal structure of the Escherichia coli OM
      lipoprotein LptE at 2.34 A. The structure reveals homology to eukaryotic LPS
      binding proteins and allowed for the prediction of an LPS-binding site, which was
      confirmed by genetic and biophysical experiments. Specific point mutations at
      this site lead to defects in OM biogenesis. We show that wild-type LptE disrupts
      LPS-LPS interactions in vitro and that these mutations decrease the ability of
      LptE to disaggregate LPS. Transmission electron microscopic imaging shows that
      LptE can disrupt LPS aggregates even at substoichiometric concentrations. We
      propose a model in which LptE functions as an LPS transfer protein in the OM
      translocon by disaggregating LPS during transport to allow for its insertion into
      the OM. 

PMID- 24938787
TI  - Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed
      [URE3] prion variants.
AB  - [URE3] is an amyloid prion of the Saccharomyces cerevisiae Ure2p, a regulator of
      nitrogen catabolism. Overproduction of Btn2p, involved in late endosome to Golgi
      protein transport, or its paralog Cur1p, cures [URE3]. Btn2p, in curing, is
      colocalized with Ure2p in a single locus, suggesting sequestration of Ure2p
      amyloid filaments. We find that most [URE3] variants generated in a btn2 cur1
      double mutant are cured by restoring normal levels of Btn2p and Cur1p, with both
      proteins needed for efficient curing. The [URE3] variants cured by normal levels
      of Btn2p and Cur1p all have low seed number, again suggesting a seed
      sequestration mechanism. Hsp42 overproduction also cures [URE3], and Hsp42p aids
      Btn2 overproduction curing. Cur1p is needed for Hsp42 overproduction curing of
      [URE3], but neither Btn2p nor Cur1p is needed for overproduction curing by the
      other. Although hsp42Delta strains stably propagate [URE3-1], hsp26Delta
      destabilizes this prion. Thus, Btn2p and Cur1p are antiprion system components at
      their normal levels, acting with Hsp42. Btn2p is related in sequence to human
      Hook proteins, involved in aggresome formation and other transport activities. 

PMID- 24938788
TI  - Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that
      stimulate breast cancer invasion and metastasis.
AB  - Extracellular vesicles such as exosomes and microvesicles (MVs) are shed by
      cancer cells, are detected in the plasma of cancer patients, and promote cancer
      progression, but the molecular mechanisms regulating their production are not
      well understood. Intratumoral hypoxia is common in advanced breast cancers and is
      associated with an increased risk of metastasis and patient mortality that is
      mediated in part by the activation of hypoxia-inducible factors (HIFs). In this
      paper, we report that exposure of human breast cancer cells to hypoxia augments
      MV shedding that is mediated by the HIF-dependent expression of the small GTPase
      RAB22A, which colocalizes with budding MVs at the cell surface. Incubation of
      naive breast cancer cells with MVs shed by hypoxic breast cancer cells promotes
      focal adhesion formation, invasion, and metastasis. In breast cancer patients,
      RAB22A mRNA overexpression in the primary tumor is associated with decreased
      overall and metastasis-free survival and, in an orthotopic mouse model, RAB22A
      knockdown impairs breast cancer metastasis. 

PMID- 24938789
TI  - Postsynaptic activity reverses the sign of the acetylcholine-induced long-term
      plasticity of GABAA inhibition.
AB  - Acetylcholine (ACh) regulates forms of plasticity that control cognitive
      functions but the underlying mechanisms remain largely unknown. ACh controls the
      intrinsic excitability, as well as the synaptic excitation and inhibition of CA1
      hippocampal pyramidal cells (PCs), cells known to participate in circuits
      involved in cognition and spatial navigation. However, how ACh regulates
      inhibition in function of postsynaptic activity has not been well studied. Here
      we show that in rat PCs, a brief pulse of ACh or a brief stimulation of
      cholinergic septal fibers combined with repeated depolarization induces strong
      long-term enhancement of GABAA inhibition (GABAA-LTP). Indeed, this enhanced
      inhibition is due to the increased activation of alpha5betagamma2 subunit
      containing GABAA receptors by the GABA released. GABAA-LTP requires the
      activation of M1-muscarinic receptors and an increase in cytosolic Ca(2+). In the
      absence of PC depolarization ACh triggered a presynaptic depolarization-induced
      suppression of inhibition (DSI), revealing that postsynaptic activity gates the
      effects of ACh from presynaptic DSI to postsynaptic LTP. These results provide
      key insights into mechanisms potentially linked with cognitive functions, spatial
      navigation, and the homeostatic control of abnormal hyperexcitable states. 

PMID- 24938791
TI  - Role of timbre memory in evaluating Stradivari violins.

PMID- 24938790
TI  - MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus
      production.
AB  - MicroRNAs (miRNAs) are small, 18-22 nt long, noncoding RNAs that act as potent
      negative gene regulators in a variety of physiological and pathological
      processes. To repress gene expression, miRNAs are packaged into RNA-induced
      silencing complexes (RISCs) that target mRNAs for degradation and/or
      translational repression in a sequence-specific manner. Recently, miRNAs have
      been shown to also interact with proteins outside RISCs, impacting cellular
      processes through mechanisms not involving gene silencing. Here, we define a
      previously unappreciated activity of miRNAs in inhibiting RNA-protein
      interactions that in the context of HIV-1 biology blocks HIV virus budding and
      reduces virus infectivity. This occurs by miRNA binding to the nucleocapsid
      domain of the Gag protein, the main structural component of HIV-1 virions. The
      resulting miRNA-Gag complexes interfere with viral-RNA-mediated Gag assembly and
      viral budding at the plasma membrane, with imperfectly assembled Gag complexes
      endocytosed and delivered to lysosomes. The blockade of virus production by miRNA
      is reversed by adding the miRNA's target mRNA and stimulated by depleting
      Argonaute-2, suggesting that when miRNAs are not mediating gene silencing, they
      can block HIV-1 production through disruption of Gag assembly on membranes.
      Overall, our findings have significant implications for understanding how cells
      modulate HIV-1 infection by miRNA expression and raise the possibility that
      miRNAs can function to disrupt RNA-mediated protein assembly processes in other
      cellular contexts. 

PMID- 24938792
TI  - Probenecid reduces infection and inflammation in acute Pseudomonas aeruginosa
      pneumonia.
AB  - The activation of inflammasome signaling mediates pathology of acute Pseudomonas
      aeruginosa pneumonia. This suggests that the inflammasome might represent a
      target to limit the pathological consequences of acute P. aeruginosa lung
      infection. Pannexin-1 (Px1) channels mediate the activation of caspase-1 and
      release of IL-1beta induced by P2X7 receptor activation. The approved drug
      probenecid is an inhibitor of Px1 and ATP release. In this study, we demonstrate
      that probenecid reduces infection and inflammation in acute P. aeruginosa
      pneumonia. Treatment of mice prior to infection with P. aeruginosa resulted in an
      enhanced clearance of P. aeruginosa and reduced levels of inflammatory mediators,
      such as IL-1beta. In addition, probenecid inhibited the release of inflammatory
      mediators in murine alveolar macrophages and human U937 cell-derived macrophages
      upon bacterial infection but not in human bronchial epithelial cells. Thus, Px1
      blockade via probenecid treatment may be a therapeutic option in P. aeruginosa
      pneumonia by improving bacterial clearance and reducing negative consequences of
      inflammation. 

PMID- 24938793
TI  - Childhood leukaemia risks: from unexplained findings near nuclear installations
      to recommendations for future research.
AB  - Recent findings related to childhood leukaemia incidence near nuclear
      installations have raised questions which can be answered neither by current
      knowledge on radiation risk nor by other established risk factors. In 2012, a
      workshop was organised on this topic with two objectives: (a) review of results
      and discussion of methodological limitations of studies near nuclear
      installations; (b) identification of directions for future research into the
      causes and pathogenesis of childhood leukaemia. The workshop gathered 42
      participants from different disciplines, extending widely outside of the
      radiation protection field. Regarding the proximity of nuclear installations, the
      need for continuous surveillance of childhood leukaemia incidence was
      highlighted, including a better characterisation of the local population. The
      creation of collaborative working groups was recommended for consistency in
      methodologies and the possibility of combining data for future analyses.
      Regarding the causes of childhood leukaemia, major fields of research were
      discussed (environmental risk factors, genetics, infections, immunity, stem
      cells, experimental research). The need for multidisciplinary collaboration in
      developing research activities was underlined, including the prevalence of
      potential predisposition markers and investigating further the infectious
      aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of
      great interest. Routes for future research were pointed out. 

PMID- 24938794
TI  - Watershed management and public health: an exploration of the intersection of two
      fields as reported in the literature from 2000 to 2010.
AB  - Watersheds are settings for health and well-being that have a great deal to offer
      the public health community due to the correspondence between the spatial form of
      the watershed unit and the importance to health and well-being of water. However,
      managing watersheds for human health and well-being requires the ability to move
      beyond typical reductionist approaches toward more holistic methods. Health and
      well-being are emergent properties of inter-related social and biophysical
      processes. This paper characterizes points of connection and integration between
      watershed management and public health and tests a new conceptual model, the
      Watershed Governance Prism, to determine the prevalence in peer-reviewed
      literature of different perspectives relating to watersheds and public health. We
      conducted an initial search of academic databases for papers that addressed the
      interface between watershed management (or governance) and public health themes.
      We then generated a sample of these papers and undertook a collaborative analysis
      informed by the Watershed Governance Prism. Our analysis found that although
      these manuscripts dealt with a range of biophysical and social determinants of
      health, there was a tendency for social factors and health outcomes to be framed
      as context only for these studies, rather than form the core of the relationships
      being investigated. At least one cluster of papers emerged from this analysis
      that represented a cohesive perspective on watershed governance and health;
      "Perspective B" on the Watershed Governance Prism, "water governance for
      ecosystems and well-being," was dominant. Overall, the integration of watershed
      management/governance and public health is in its infancy. 

PMID- 24938795
TI  - Incorporating carbon storage into the optimal management of forest insect pests:
      a case study of the southern pine beetle (Dendroctonus frontalis Zimmerman) in
      the New Jersey Pinelands.
AB  - Forest insect pest disturbance is increasing in certain areas of North America as
      many insect species, such as the southern pine beetle, expand their range due to
      a warming climate. Because insect pests are beginning to occupy forests that are
      managed for multiple uses and have not been managed for pests before, it is
      becoming increasingly important to determine how forests should be managed for
      pests when non-timber ecosystem services are considered in addition to
      traditional costs and revenues. One example of a service that is increasingly
      considered in forest management and that may affect forest pest management is
      carbon sequestration. This manuscript seeks to understand whether the
      incorporation of forest carbon sequestration into cost-benefit analysis of
      different forest pest management strategies affects the financially optimal
      strategy. We examine this question through a case study of the southern pine
      beetle (SPB) in a new area of SPB expansion, the New Jersey Pinelands National
      Reserve (NJPR). We utilize a forest ecology and economics model and include field
      data from the NJPR as well as outbreak probability statistics from previous
      years. We find under the majority of scenarios, incorporating forest carbon
      sequestration shifts the financially optimal SPB management strategy from
      preventative thinning toward no management or reactionary management in forest
      stands in New Jersey. These results contradict the current recommended treatment
      strategy for SPB and signify that the inclusion of multiple ecosystem services
      into a cost-benefit analysis may drastically alter which pest management strategy
      is economically optimal. 

PMID- 24938796
TI  - Brain death induces the alteration of liver protein expression profiles in
      rabbits.
AB  - At present, there is no accurate method for evaluating the quality of liver
      transplant from a brain-dead donor. Proteomics are used to investigate the
      mechanisms involved in brain death-induced liver injury and to identify sensitive
      biomarkers. In the present study, age- and gender-matched rabbits were randomly
      divided into the brain death and sham groups. The sham served as the control. A
      brain-death model was established using an intracranial progressive pressurized
      method. The differentially expressed proteins extracted from the liver tissues of
      rabbits that were brain-dead for 6 h in the two groups were determined by two
      dimensional gel electrophoresis and matrix-assisted laser desorption ionization
      time of flight mass spectrometry. Although there was no obvious functional and
      morphological difference in 2, 4 and 6 h after brain death, results of the
      proteomics analysis revealed 973+/-34 and 987+/-38 protein spots in the control
      and brain death groups, respectively. Ten proteins exhibited a >=2-fold
      alteration. The downregulated proteins were: aldehyde dehydrogenase, runt-related
      transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate-cysteine
      ligase regulatory subunit and microsomal cytochrome B5. By contrast, the
      expression of dihydropyrimidinase-related protein 4, peroxiredoxin-6, 3
      phosphoinositide-dependent protein kinase-1, 3-mercaptopyruvate and alcohol
      dehydrogenase were clearly upregulated. Immunohistochemistry and western blot
      analysis results revealed that the expression of RUNX1 was gradually increased in
      a time-dependent manner in 2, 4, and 6 h after brain death. In conclusion,
      alteration of the liver protein expression profile induced by brain death
      indicated the occurrence of complex pathological changes even if no functional or
      morphological difference was identified. Thus, RUNX1 may be a sensitive predict
      factor for evaluating the quality of brain death donated liver.

PMID- 24938797
TI  - Streptococcus pneumoniae secretes a glyceraldehyde-3-phosphate dehydrogenase,
      which binds haemoglobin and haem.
AB  - Streptococcus pneumoniae is a gram positive encapsulated bacterium responsible of
      septicaemia and upper respiratory infections in children. This pathogen requires
      iron to survive in the host, which it can obtain of haemoglobin (Hb) or haem.
      Only two Hb-binding membrane proteins have been identified up to now. However it
      is unknown whether this pathogen secretes proteins in order to scavenge iron from
      the Hb or haem. Therefore, in order to explore these possibilities, cellular
      growth of S. pneumoniae was tested with several alternative iron supplies. The
      bacterial growth was supported with iron, Hb and haem. Additionally, S.
      pneumoniae expressed and secreted a protein of 38 kDa which was purified and
      characterized as Hb and haem-binding protein. This protein was also identified by
      mass spectrometry as glyceraldehyde-3-phosphate dehydrogenase. Our overall
      results suggest that S. pneumoniae secretes a protein capable of binding two
      usefull iron sources for this bacterium (Hb and haem). This protein could be
      playing a dynamic role in the success of the invasive and infective processes of
      this pathogen. 

PMID- 24938798
TI  - Estrogen stimulates expression of chicken hepatic vitellogenin II and very low
      density apolipoprotein II through ER-alpha.
AB  - Steroid hormones and their receptors play pivotal roles throughout vertebrate
      reproduction and development. Egg formation in avian species is a prime example.
      The synthesis of egg yolk proteins by the liver is highly dependent on estrogen.
      Two major components of the yolk protein precursors, vitellogenin II (VTG II) and
      very low-density apolipoprotein II (ApoVLDL II), are synthesized in the liver of
      hens under estrogen stimulation and are subsequently transferred via the blood to
      the developing oocytes. Estrogen-inducible transcription can be mediated through
      estrogen receptors (ERs) (ER-alpha and ER-beta) or through G protein-coupled
      receptor 30 (GPR30), but the exact participation of the individual receptor is
      not clear. Here, we determine the relative contribution of each transduction
      pathway in the synthesis of VTG II and ApoVLDL II in the hepatocytes by using
      selective compounds that are known to specifically interact with each of the ERs
      and GPR30. 17beta-Estradiol and propyl pyrazole triol (PPT, ER-alpha agonist)
      induced increase in VTG II and ApoVLDL II mRNA expressions in a dose-dependent
      manner. A high concentration of diarylpropionitrile (DPN, which preferentially
      motivates ER-beta) slightly stimulated the expression of VTG II and ApoVLDL II
      mRNAs. However, G-1 (a GPR30 agonist) failed to display any stimulating role.
      Methyl-piperidino-pyrazole (a highly selective ER-alpha antagonist) fully blocked
      the expression of both yolk precursors, which were upregulated by 17beta
      estradiol, PPT, and DPN. Considering that DPN can also provoke the action of ER
      alpha at high concentration, this excludes the participation of ER-beta and
      supports the role of ER-alpha. The aforementioned results indicate that estrogen
      stimulates the expression of VTG II and ApoVLDL II mRNAs predominantly through ER
      alpha in the chicken liver.

PMID- 24938799
TI  - Cryopreservation of epididymal sperm from ibexes (Capra pyrenaica) using short
      equilibration time with glycerol.
AB  - Two experiments were conducted to study the effect of shortening the
      equilibration time with the cryoprotectant glycerol before freezing epididymal
      sperm recovered postmortem from Iberian ibex. In the first experiment, the
      standard equilibration time of 3 hours was compared with 2 hours, and subjective
      sperm motility and quality of movement were greater (P < 0.05) in the latter
      group. In the second experiment, reducing the equilibration time from 2 hours to
      15 minutes did not affect sperm motility (evaluated subjectively and
      objectively), viability, acrosomal integrity, or membrane functional integrity.
      In conclusion, shortening the equilibration time can be used as a technique to
      simplify the cryopreservation process and this provides practical advantages
      under field conditions.

PMID- 24938801
TI  - Effect of time and dose of recombinant follicle stimulating hormone agonist on
      the superovulatory response of sheep.
AB  - The objective of this study was to determine the superovulatory potential of a
      single-chain analog of human FSH (Fcalpha) when administered to ewes either 3
      days before, or coincident with, simulated luteolysis (pessary removal [PR]). A
      total of 40 animals were randomly assigned to receive Fcalpha at doses of 0.62,
      1.25, or 2.5 IU/kg of body weight (bwt) 3 days before PR or 0.31, 0.62, 1.25, or
      2.5 IU/kg of bwt at PR. Control ewes received protein without FSH activity. Blood
      samples were collected during the periovulatory period and ovarian tissue was
      collected 11 days after PR. Ovulation rate did not differ from the control group
      in ewes receiving the smallest doses of Fcalpha (0.31 and 0.62 IU/kg). However, a
      significant superovulatory response was noted in sheep receiving Fcalpha at doses
      of 1.25 and 2.5 IU/kg and this response was comparable in animals receiving the
      largest dose levels of Fcalpha at, or 3 days before, PR. The interval between PR
      and the LH surge was significantly extended and the LH surges were less
      synchronous in animals receiving Fcalpha at PR when compared with animals
      receiving the potent FSH agonist 3 days before PR. Taken together, these data
      indicate that the human single-chain gonadotropin with FSH activity promotes
      superovulation in ewe lambs in the breeding season. A single injection of the
      recombinant gonadotropin 3 days before luteolysis synchronizes the LH surge. The
      use of the single-chain analog of FSH in assisted reproduction for domestic
      animals is likely to be of practical significance as an alternative to
      conventional gonadotropins in superovulation protocols in livestock species.

PMID- 24938800
TI  - Serum testosterone, progesterone, and estradiol concentrations and sexual
      maturation in spotted seals (Phoca largha).
AB  - Spotted seals (Phoca largha) are ice-breeding phocid found in eight different
      breeding colonies all over the world. They exhibit a seasonal breeding pattern,
      with annual and synchronous cycles; however, little is known about their
      reproductive endocrinology. In this study, we measured serum testosterone,
      progesterone, and 17beta-estradiol concentrations in captive spotted seals
      (simple number: female n = 68; male n = 89) throughout a full reproductive cycle.
      Males that were older than 4 years had significant testosterone fluctuations and
      were, therefore, classified as sexually mature. These animals show significant
      seasonal changes in testosterone levels, with average peak concentrations of
      10.81 +/- 9.57 nmol/L (+/-SD) from November to February, compared with mean
      concentrations of 1.42 +/- 3.09 nmol/L throughout the remainder of the year.
      Females that reported a significant variation in progesterone concentrations and
      were older than 4 years were considered to be sexually mature. In these females,
      progesterone levels increased in February, remained elevated for 7 months with a
      mean value of 37.39 +/- 17.03 nmol/L, and then dropped to 0.74 +/- 0.54 nmol/L.
      Serum 17beta-estradiol levels were also found to be significantly increased in
      January, remained so for 8 months (15.80 +/- 14.15 ng/L), and then declined after
      August (7.77 +/- 6.78 ng/L). In seals, mating typically occurs in February and
      March, 1 month after the observed peaks in testosterone and estradiol
      concentrations and corresponding to the increase in progesterone. A moderate
      positive correlation between testosterone and progesterone concentrations in
      sexually mature males was also observed (Spearman rho, r = 0.63, P < 0.01). In
      sexually immature females, progesterone and estradiol concentrations were found
      to be significantly lower than those in mature females. Finally, the observed
      patterns of estradiol and progesterone in sexually mature females suggest that
      embryonic diapause or successful implantation occurs in August.

PMID- 24938802
TI  - Use of a single injection of long-acting recombinant bovine FSH to superovulate
      Holstein heifers: a preliminary study.
AB  - Our objective was to compare several experimental preparations of a single
      injection of long-acting recombinant bovine FSH (rbFSH; types A and B) to a
      porcine pituitary-derived FSH (Folltropin) to superovulate Holstein dairy
      heifers. Nonlactating, nonpregnant virgin Holstein heifers (n = 56) aged 12 to 15
      months were randomly assigned to one of four superstimulatory treatments.
      Beginning at a random stage of the estrous cycle, all follicles greater than 5 mm
      were aspirated. Thirty-six hours later, heifers received an intravaginal P4
      device and superstimulatory treatments were initiated. Treatments were (1) 300 mg
      of pituitary-derived FSH (Folltropin) administered in eight decreasing doses over
      a period of 3.5 days; (2) a single injection of 50 MUg of A-rbFSH; (3) a single
      injection of 100 MUg of A-rbFSH; and (4) a single injection of 50 MUg of B-rbFSH.
      All heifers received 25 mg PGF2alpha at 48 and 72 hours after the insertion of P4
      device. At 84 hours after insertion, P4 devices were removed, and ovulation was
      induced 24 hours later with hCG (2500 IU). Heifers were inseminated at 12 and 24
      hours after hCG treatment. The number of ovulatory follicles was greatest for
      heifers treated with Folltropin and B50-rbFSH, least for heifers treated with A50
      rbFSH, and was intermediate for heifers treated with A100-rbFSH (25.7 +/- 3.2,
      18.9 +/- 3.2, 5.9 +/- 0.9, and 16.6 +/- 3.1, respectively; P < 0.001). The number
      of corpora lutea was greatest for heifers treated with Folltropin, B50-rbFSH, and
      A100-rbFSH, and least for heifers treated with A50-rbFSH (19.1 +/- 2.4, 16.1 +/-
      3.0, 15.9 +/- 2.9, and 2.6 +/- 0.9, respectively; P < 0.001). The number of good
      quality embryos differed among treatments and was greatest for heifers treated
      with B50-rbFSH, Folltropin, and A100-rbFSH and least for heifers treated with A50
      rbFSH (7.6 +/- 2.4, 6.5 +/- 1.7, 4.3 +/- 1.5, and 0.8 +/- 0.5, respectively; P <
      0.001). In conclusion, a single injection of a preparation of long-acting rbFSH
      (either 100 MUg of A-rbFSH or 50 MUg of B-rbFSH but not 50 MUg of A-rbFSH)
      produced similar superovulatory responses resulting in the production of good
      quality embryos when compared with a pituitary-derived FSH preparation
      administered twice daily for 4 days. More studies using different types of cattle
      and different doses of rbFSH are needed to confirm the findings reported in this
      preliminary study.

PMID- 24938803
TI  - Better research, better writing, better publishing.

PMID- 24938804
TI  - Forget translations - rewrite in the requested language.

PMID- 24938805
TI  - Prevention of intestinal obstruction reveals progressive neurodegeneration in
      mutant TDP-43 (A315T) mice.
AB  - BACKGROUND: Intraneuronal inclusions of TAR DNA-binding protein 43 (TDP-43) have
      been found in the majority of Amyotrophic Lateral Sclerosis (ALS) patients.
      Mutations in the gene encoding TDP-43 cause familial ALS. Transgenic mice
      expressing mutant TDP-43 with one such mutation (TDP-43 (A315T)) under control of
      the murine prion promoter develop motor symptoms, but their use is currently
      hampered by sudden death. We aimed to understand and overcome the cause of sudden
      death in TDP-43 (A315T) mice. Since intestinal obstruction was suspected to be
      the cause, intestinal motility of TDP-43 (A315T) mice was studied in an ex-vivo
      pellet propulsion assay. The effect on the enteric and motor phenotype was
      assessed, both in animals on normal chow or on a jellified fiber deprived diet,
      aimed at preventing intestinal obstruction. RESULTS: The frequency of the
      propulsive motor complexes was significantly reduced in the colon of TDP-43
      (A315T) compared to non transgenic (NTG) mice. Immunohistochemistry revealed
      significant enlargement in size and reduction in number of the nitric oxide
      synthase (NOS) neurons in the myenteric plexus of TDP-43 (A315T) mice. Prevention
      of intestinal obstruction by jellified food abolished sudden death, allowing the
      motor phenotype to develop and slowly progress with a more pronounced
      degeneration of upper and lower motor axons. A downregulation of endogenous TDP
      43 mRNA and protein levels was observed prior to neurodegeneration. CONCLUSION:
      TDP-43 (A315T) mice suffer from intestinal dysmotility due to degeneration of NOS
      neurons in the myenteric plexus. Feeding the mice jellified food prevents sudden
      death and allows the motor phenotype to progress.

PMID- 24938806
TI  - Heavy metal and organic contaminants in mangrove ecosystems of China: a review.
AB  - China's rapid economic growth has been accompanied by increasing environmental
      pollution. Mangrove ecosystems are now facing greater pollution pressures due to
      elevated chemical discharges from various land-based sources. Data on the levels
      of heavy metals and organic pollutants in mangrove compartments (sediments,
      plants, zoobenthos, and fish) in China over the past 20 years have been
      summarized to evaluate the current pollution status of the mangrove ecosystem.
      Overall, the Pearl River and Jiulong River estuaries were severely polluted
      spots. Concentrations of Cu, Zn, Cd, and Pb in mangrove sediments of Guangdong,
      Fujian, and Hong Kong were higher than those from Guangxi and Hainan. The
      pollution status was closely linked to industrialization and urbanization. The
      highest concentrations of polycyclic aromatic hydrocarbons (PAHs) were found in
      mangrove sediments from Hong Kong, followed by Fujian and Guangdong. Mangrove
      plants tend to have low-enriched ability for heavy metals and organic pollutants.
      Much higher levels of Pb, Cd, and Hg were observed in mollusks.

PMID- 24938808
TI  - Climate change and air pollution jointly creating nightmare for tourism industry.
AB  - The objective of the study is to examine the long-run and causal relationship
      between climate change (i.e., greenhouse gas emissions, hydrofluorocarbons, per
      fluorocarbons, and sulfur hexafluoride), air pollution (i.e., methane emissions,
      nitrous oxide emissions, and carbon dioxide emissions), and tourism development
      indicators (i.e., international tourism receipts, international tourism
      expenditures, natural resource depletion, and net forest depletion) in the
      World's largest regions. The aggregate data is used for robust analysis in the
      South Asia, the Middle East and North Africa, sub-Saharan Africa, and East Asia
      and the Pacific regions, over a period of 1975-2012. The results show that
      climatic factors and air pollution have a negative impact on tourism indicators
      in the form of deforestation and natural resource depletion. The impact is
      evident, as we have seen the systematic eroding of tourism industry, due to
      severe changes in climate and increasing strain of air pollution. There are
      several channels of cause-effect relationship between the climatic factors, air
      pollution, and tourism indicators in the World's region. The study confirms the
      unidirectional, bidirectional, and causality independent relationship between
      climatic factors, air pollution, and tourism indicators in the World. It is
      conclusive that tourism industry is facing all time bigger challenges of reduce
      investment, less resources, and minor importance from the government agencies
      because of the two broad challenges, i.e., climate change and air pollution,
      putting them in a dismal state.

PMID- 24938807
TI  - The flux of radionuclides in flowback fluid from shale gas exploitation.
AB  - This study considers the flux of radioactivity in flowback fluid from shale gas
      development in three areas: the Carboniferous, Bowland Shale, UK; the Silurian
      Shale, Poland; and the Carboniferous Barnett Shale, USA. The radioactive flux
      from these basins was estimated, given estimates of the number of wells developed
      or to be developed, the flowback volume per well and the concentration of K
      (potassium) and Ra (radium) in the flowback water. For comparative purposes, the
      range of concentration was itself considered within four scenarios for the
      concentration range of radioactive measured in each shale gas basin, the
      groundwater of the each shale gas basin, global groundwater and local surface
      water. The study found that (i) for the Barnett Shale and the Silurian Shale,
      Poland, the 1 % exceedance flux in flowback water was between seven and eight
      times that would be expected from local groundwater. However, for the Bowland
      Shale, UK, the 1 % exceedance flux (the flux that would only be expected to be
      exceeded 1 % of the time, i.e. a reasonable worst case scenario) in flowback
      water was 500 times that expected from local groundwater. (ii) In no scenario was
      the 1 % exceedance exposure greater than 1 mSv-the allowable annual exposure
      allowed for in the UK. (iii) The radioactive flux of per energy produced was
      lower for shale gas than for conventional oil and gas production, nuclear power
      production and electricity generated through burning coal.

PMID- 24938809
TI  - Impact of Parthenium weeds on earthworms (Eudrilus eugeniae) during
      vermicomposting.
AB  - The aim of this work is to evaluate the effect of Parthenium-mediated compost on
      Eudrilus eugeniae during the process of vermicomposting. Nine different
      concentrations of Parthenium hysterophorus and cow dung mixtures were used to
      assess toxicity. The earthworms' growth, fecundity and antioxidant enzyme levels
      were analysed every 15 days. The antioxidant activities of enzymes [superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], considered as
      biomarkers, indicate the biochemical and oxidative stresses due to the toxin from
      Parthenium weeds. The earthworms' growth, biomass gain, cocoon production and
      antioxidant enzymes were in a low level in a high concentration of P.
      hysterophorus (without cow dung). The results clearly indicated that appropriate
      mixing of P. hysterophorus quantity is an essential factor for the survival of
      earthworms without causing any harm.

PMID- 24938810
TI  - Alterations in neurobehaviors and inflammation in hippocampus of rats induced by
      oral administration of microcystin-LR.
AB  - Microcystin-LR (MC-LR) is a widely studied toxic peptide secreted by certain
      water blooms of cyanobacteria that exhibit hepatotoxicity and neural toxicity.
      This study aimed to observe the neurotoxic effects of low-dose MC-LR exposure by
      oral administration. Male Sprague-Dawley (SD) rats were administered orally every
      2 days for 8 weeks with pure water and 0.2, 1.0, and 5.0 MUg/kg MC-LR. The Morris
      water maze test was used to assess the spatial learning and memory capability of
      rats. The activation of astrocytes and nitric oxide synthase (NOS) was evaluated
      by immunohistochemistry, and concentrations of nitric oxide (NO) in rat
      hippocampus were analyzed. Slight liver dysfunction was observed in the 5.0
      MUg/kg MC-LR-treated rats. Impairment of spatial learning and memory was also
      observed in the 5.0 MUg/kg MC-LR-treated rats. Astrocytes in the hippocampus of
      the 5.0 MUg/kg MC-LR-treated rats showed enhanced activation and cell density;
      the inflammatory indicators, NOS and NO, increased in accordance with astrocyte
      activation. This study showed that oral exposure of MC-LR had adverse affects on
      neurobehaviors, and induced inflammation in memory-related brain regions.

PMID- 24938811
TI  - Extraction of Sudan dyes from environmental water by hemimicelles-based magnetic
      titanium dioxide nanoparticles.
AB  - A novel method for the extraction of Sudan dyes including Sudan I, II, III, and
      IV from environmental water by magnetic titanium dioxide nanoparticles
      (Fe3O4@TiO2) coated with sodium dodecylsulfate (SDS) as adsorbent was reported.
      Fe3O4@TiO2 was synthesized by a simple method and was characterized by
      transmission electron microscopy, Fourier-transform infrared spectrometry, and
      vibrating sample magnetometer. The magnetic separation was quite efficient for
      the adsorption and desorption of Sudan dyes. The effect of the amount of SDS,
      extraction time, pH, desorption condition, maximal extraction volume, and humic
      acid on the extraction process were investigated. This method was employed to
      analyze three environmental water samples. The results demonstrated that our
      proposed method had wide linear range (25-5,000 ng L(-1)) with a good linearity
      (R (2) > 0.999) and low detection limits (2.9-7.3 ng L(-1)). An enrichment factor
      of 1,000 was achieved. In all three spiked levels (25, 250, and 2,500 ng L(-1)),
      the recoveries of Sudan dyes were in the range of 86.9-93.6 %. The relative
      standard deviations obtained were ranging from 2.5 to 9.3 %. That is to say, the
      new method was fast and effective for the extraction of Sudan dye from
      environmental water.

PMID- 24938812
TI  - Feeding preferences of two detritivores related to size and metal content of
      leaves: the crustaceans Atyaephyra desmarestii (Millet) and Echinogammarus
      meridionalis (Pinkster).
AB  - The equilibrium of the structure and functioning of freshwater ecosystems is
      dependent of detritivores that link all the other functional groups. The
      preference for feeding leaves with different diameters (particle size) and leaves
      with metal contamination (several concentrations of the essential metals copper
      and zinc) were determined for two detritivores, the decapod Atyaephyra
      desmarestii and the amphipod Echinogammarus meridionalis. Several no-choice and
      multi-choice assays were done to determinate which leaf diameter the amphipod and
      the decapod species would eat when they had or not had alternatives available and
      include a set of dual-choice assays with contaminated and uncontaminated foods.
      No significant preference was shown by either species relative to the diameter of
      leaves, either on no-choice or multi-choice assays. The presence of essential
      metals on food did not had any influence on the feeding choice of these organisms
      over the concentration range studied. Both showed no preference on ingesting food
      spiked with these essential metals, except E. meridionalis which preferred
      ingesting leaves with 2.19 MUg.l(-1) of copper instead of uncontaminated leaves.
      For further works, despite no preference for leaves with a certain diameter, the
      leaves with 0.70 cm (0.385 cm(2)of area) and with 0.50 cm (1.767 cm(2) of area)
      should be used for A. desmarestii and E. meridionalis, respectively. Furthermore,
      to maintain E. meridionalis, the diet should include some percentage of copper in
      order to accomplish metabolic needs.

PMID- 24938813
TI  - In vivo effects of metaldehyde on Pacific oyster, Crassostrea gigas: comparing
      hemocyte parameters in two oyster families.
AB  - Pollutants via run-off into the ocean represent a potential threat to marine
      organisms, especially bivalves such as oysters living in coastal environments.
      These organisms filter large volumes of seawater and may accumulate contaminants
      within their tissues. Pesticide contamination in water could have a direct or
      indirect toxic action on tissues or cells and could induce alteration of immune
      system. Bivalve immunity is mainly supported by hemocytes and participates
      directly by phagocytosis to eliminate pathogens. Some studies have shown that
      pesticides can reduce immune defences and/or modify genomes in vertebrates and
      invertebrates. Metaldehyde is used to kill slugs, snails and other terrestrial
      gastropods. Although metaldehyde has been detected in surface waters, its effects
      on marine bivalves including the Pacific oyster, Crassostrea gigas, have never
      been studied. Given the mode of action of this molecule and its targets
      (molluscs), it could be potentially more toxic to oysters than other pesticides
      (herbicides, fungicides, insecticides, etc.). Effects of metaldehyde on oyster
      hemocyte parameters were thus monitored through in vivo experiments based on a
      short-term exposure. In this work, metaldehyde at 0.1 MUg/L, which corresponds to
      an average concentration detected in the environment, modulated hemocyte
      activities of Pacific oysters after an in vivo short-term contact. Individuals
      belonging to two families showed different behaviours for some hemocyte
      activities after contamination by metaldehyde. These results suggested that
      effects of pollutants on oysters may differ from an individual to another in
      relation to genetic diversity. Finally, it appears essential to take an interest
      in the effects of metaldehyde on a wide variety of aquatic invertebrates
      including those that have a significant economic impact. 

PMID- 24938814
TI  - Particulate matter in the indoor and outdoor air of a gymnasium and a fronton.
AB  - An indoor/outdoor monitoring programme of PM10 was carried out in two sports
      venues (a fronton and a gymnasium). Levels always below 50 MUg m(-3) were
      obtained in the fronton and outdoor air. Due to the climbing chalk and the
      constant process of resuspension, concentrations above 150 MUg m(-3) were
      registered in the gymnasium. The chalk dust contributed to CO3 (2-)
      concentrations of 32 +/- 9.4 MUg m(-3) in this sports facility, which
      represented, on average, 18 % of the PM10 mass. Here, the carbonate levels were
      128 times higher than those registered outdoors. Much lower concentrations,
      around 1 MUg m(-3), were measured in the fronton. The chalk dust is also
      responsible for the high Mg(2+) concentrations in the gym (4.7 +/- 0.89 MUg m(
      3)), unfolding a PM10 mass fraction of 2.7 %. Total carbon accounted for almost
      30 % of PM10 in both indoor spaces. Aerosol size distributions were bimodal and
      revealed a clear dependence on physical activities and characteristics of the
      sports facilities. The use of climbing chalk in the gymnasium contributed
      significantly to the coarse mode. The average geometric mean diameter, geometric
      standard deviation and total number of coarse particles were 0.77 MUm, 2.79 cm(
      3) and 28 cm(-3), respectively.

PMID- 24938816
TI  - Relationship between geographical origin and contents of Pb, Cd, and Cr in honey
      samples from the state of Parana (Brazil) with chemometric approach.
AB  - The aim of this study was to determine the trace elements, Pb, Cd, and Cr in
      honey samples from eight different regions from the state of Parana (Brazil),
      using slurry sampling graphite furnace atomic absorption spectrometry.
      Chemometric analysis (principal component analysis (PCA)) was applied to classify
      honey samples according to their levels of the trace elements Pb, Cd, and Cr,
      which is also related to the geographical origin of honey samples. The mean
      concentration for the elements followed the order Pb > Cr > > Cd. The mean values
      were 200 +/- 76, 88 +/- 14, and 4.1 +/- 4 ng g(-1) for Pb, Cr, and Cd,
      respectively. It could be verified that honey samples are geographically
      separated, especially with regard to Pb and Cd contents. Thus, honey can be
      considered a bioindicator of environmental contamination, suggesting possible
      contamination in soil, water, and air. This contamination can be related to
      natural or anthropogenic sources present in the study regions.

PMID- 24938815
TI  - Evaluation of antibiotic mobility in soil associated with swine-slurry soil
      amendment under cropping conditions.
AB  - Interest in identifying pools of antibacterial-resistance genes has grown over
      the last decade, with veterinary antibiotics (VAs) receiving particular
      attention. In this paper, a mesoscale study aimed at evaluating the vertical
      transport of common VAs-namely, fluoroquinolones, tetracyclines, sulfonamides,
      and lincosamides in agricultural soil subjected to drip irrigation-was performed
      under greenhouse conditions. Accordingly, leachates of cropped and uncropped
      soil, amended with swine-slurry leading to 19-38 MUg kg(-1) (dry mass)
      antibiotics in the soil, were analyzed over the course of the productive cycle of
      a lettuce (42 days) with three sampling campaigns (N = 24). High lincomycin (LCM)
      concentrations (30-39 MUg L(-1)) were detected in the leachates collected from
      the swine-slurry-amended soil. The highest LCM mass recovered in the leachates
      (30.1 +/- 1.63 %) was obtained from cropped experimental units. In addition, the
      LCM leaching constant and its leaching potential as obtained from the first-order
      model were higher in the leachates from the cropped experimental units. Lower
      concentrations of sulfadimethoxine were also detected in leachates and in soil.
      Enrofloxacin and oxytetracycline occurred only in soil, which is consistent with
      high soil interaction.

PMID- 24938817
TI  - Ecotoxicological effects on the earthworm Eisenia fetida following exposure to
      soil contaminated with imidacloprid.
AB  - Imidacloprid, a neonicotinoid insecticide, has been used widely in agriculture
      worldwide. The adverse effects of imidacloprid on exposed biota have brought it
      increasing attention. However, knowledge about the effects of imidacloprid on
      antioxidant defense systems and digestive systems in the earthworm is vague and
      not comprehensive. In the present study, the changes in the activity of
      superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), cellulase, reactive
      oxygen species (ROS), and malondialdehyde (MDA) in the earthworm Eisenia fetida
      exposed to artificial soil treated with imidacloprid were examined
      systematically. The results showed that the activity of these biomarkers was
      closely related to the dose and duration of the exposure to imidacloprid. The
      activity of SOD was stimulated significantly at doses of 0.66 and 2 mg kg(-1)
      imidacloprid but markedly inhibited at a dose of 4 mg kg(-1) imidacloprid with
      prolonged exposure. The activities of CAT and POD increased irregularly at 0.2-4
      mg kg(-1) imidacloprid over different exposure times. The level of ROS at a dose
      of 2 or 4 mg kg(-1) imidacloprid was significantly increased over the entire
      exposure period. When the concentration of imidacloprid was above 0.66 mg kg(-1),
      the balance of the activity of the antioxidant enzymes and ROS level was
      interrupted. The activity of cellulase decreased significantly with prolonged
      exposure. At the stress of 4 mg kg(-1) imidacloprid, the content of MDA was
      significantly increased with increasing exposure time. The results of the present
      study suggest that imidacloprid has a potentially harmful effect on E. fetida and
      may be helpful for assessment of the risk of imidacloprid to the soil ecosystem
      environment. However, to obtain more comprehensive toxicity data, it is necessary
      to investigate the effects of imidacloprid on earthworm using native soils in the
      future work.

PMID- 24938818
TI  - Concentration and composition variations of metals in the outdoor PM10 of
      elementary schools during river dust episodes.
AB  - Aeolian river dust can seriously affect the air quality in central Taiwan. The
      main purpose of this study was to assess the concentration variations of PM10 and
      metals at different elementary schools during river dust episodes. River dust
      samples were taken from eight sites in the main bare soil areas of the Choshui
      River. PM10 aerosols from four elementary schools in Yulin County were collected
      by means of high-volume samplers. Fifteen elements (Fe, Al, Ca, Mg, Mn, Zn, Ti,
      Ni, V, Cr, As, Pb, Cu, Co, and Cd) in the river dust and PM10 were analyzed in
      this study. The coefficients of divergence (CDs) were obtained by comparing the
      metal compositions in PM10 aerosols at the four schools on the sampling days with
      the mean metal contents in the river soil samples as reference. The CD values
      showed that metal compositions in the aerosols at high-exposure sites during
      river dust episodes were similar to those compositions in the river dust. The
      concentrations of PM10 at the high-exposure schools during river dust episodes
      were much higher than those during non-river-dust episodes. This study also
      indicated that at the high-exposure sites, both the PM10 and metal concentrations
      were higher than at the low-exposure and control sites, not only during the river
      dust episodes, but also after the river dust episodes. The concentrations of
      toxic metals (Ni, Cr, As, and Cd) at the high-exposure sites were about 11.3
      times higher during the river dust episodes (189 ng/m(3)) than during non-river
      dust episodes (16.7 ng/m(3)) and about 8.9 times higher during the same periods
      at the control site (21.3 ng/m(3)).

PMID- 24938820
TI  - Identification of heat-related ESTs in moth bean through suppression subtraction
      hybridization.
AB  - Moth bean (Vigna aconitifolia (Jacq.) Marechal), an important grain-legume crop
      grown in hot desert regions of Thar, under scorching sun rays, was investigated
      for heat tolerance at molecular level. In the present study, we constructed a
      forward suppression subtractive hybridization (SSH) cDNA library of heat tolerant
      genotype RMO-40 to identify genes expressing under delayed response to elevated
      temperature. Heat induction was carried out by exposing 14-day-old seedlings to
      elevated temperature of 42  degrees C for 30 min. A total of 125 unigenes (33
      contigs and 92 singletons) were derived by cluster assembly and sequence
      alignment of 200 ESTs; out of 125 unigenes, 21 (16 %) were found to be novel to
      moth bean. Gene ontology functional classification terms were retrieved for 98
      (78.4 %) unigenes of which 73 (58.4 %) ESTs were functionally annotated (GO
      consensus) where 19 unigenes were annotated with 11 enzyme commission (EC) codes
      and were mapped to 25 different KEGG pathways. We have identified a majority of
      heat-shock proteins (constituting 35 % of the present library) aiding heat stress
      tolerance to moth bean. An expression level of 22 ESTs generated from the above
      SSH cDNA library was studied through semiquantitative RT-PCR assay simultaneously
      under 5 and 30 min of heat stress at 42  degrees C.

PMID- 24938819
TI  - A review of the direct and indirect effects of neonicotinoids and fipronil on
      vertebrate wildlife.
AB  - Concerns over the role of pesticides affecting vertebrate wildlife populations
      have recently focussed on systemic products which exert broad-spectrum toxicity.
      Given that the neonicotinoids have become the fastest-growing class of
      insecticides globally, we review here 150 studies of their direct (toxic) and
      indirect (e.g. food chain) effects on vertebrate wildlife--mammals, birds, fish,
      amphibians and reptiles. We focus on two neonicotinoids, imidacloprid and
      clothianidin, and a third insecticide, fipronil, which also acts in the same
      systemic manner. Imidacloprid and fipronil were found to be toxic to many birds
      and most fish, respectively. All three insecticides exert sub-lethal effects,
      ranging from genotoxic and cytotoxic effects, and impaired immune function, to
      reduced growth and reproductive success, often at concentrations well below those
      associated with mortality. Use of imidacloprid and clothianidin as seed
      treatments on some crops poses risks to small birds, and ingestion of even a few
      treated seeds could cause mortality or reproductive impairment to sensitive bird
      species. In contrast, environmental concentrations of imidacloprid and
      clothianidin appear to be at levels below those which will cause mortality to
      freshwater vertebrates, although sub-lethal effects may occur. Some recorded
      environmental concentrations of fipronil, however, may be sufficiently high to
      harm fish. Indirect effects are rarely considered in risk assessment processes
      and there is a paucity of data, despite the potential to exert population-level
      effects. Our research revealed two field case studies of indirect effects. In
      one, reductions in invertebrate prey from both imidacloprid and fipronil uses led
      to impaired growth in a fish species, and in another, reductions in populations
      in two lizard species were linked to effects of fipronil on termite prey.
      Evidence presented here suggests that the systemic insecticides, neonicotinoids
      and fipronil, are capable of exerting direct and indirect effects on terrestrial
      and aquatic vertebrate wildlife, thus warranting further review of their
      environmental safety.

PMID- 24938822
TI  - Oxygen insertion reactions of mixed N-heterocyclic carbene-oxazolinylborato zinc
      alkyl complexes.
AB  - We report the synthesis of a new mixed oxazoline-carbene scorpionate ligand,
      bis(4,4-dimethyl-2-oxazolinyl)(1-mesitylimidazolyl)phenylborate
      (PhB(Ox(Me2))2Im(Mes)). Reactions of the protonated form PhB(Ox(Me2))2(Im(Mes)H)
      with dialkylzinc compounds provide four-coordinate zinc alkyl complexes, and X
      ray diffraction studies of the {PhB(Ox(Me2))2Im(Mes)}ZnR (R = Me, Et) compounds
      show significant structural distortions involving the R groups shifting away from
      the carbene donor. The reaction of {PhB(Ox(Me2))2Im(Mes)}ZnEt (3) and O2 provides
      an isolable mononuclear zinc alkylperoxide {PhB(Ox(Me2))2Im(Mes)}ZnOOEt (4),
      which has been characterized by single crystal X-ray diffraction and (17)O NMR
      spectroscopy.

PMID- 24938821
TI  - Undariase, a direct-acting fibrin(ogen)olytic enzyme from Undaria pinnatifida,
      inhibits thrombosis in vivo and exhibits in vitro thrombolytic properties.
AB  - A direct-acting fibrinolytic serine protease named undariase possessing
      anticoagulant and antiplatelet properties was purified from Undaria pinnatifida.
      Undariase showed a molecular weight of 50 kDa by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. It displayed
      a strong fibrin zymogram lysis band corresponding to the same molecular mass. The
      N-terminal sequence of undariase, LTATTCEELAAAPTD, does not match with any known
      fibrinolytic enzyme. The enzyme was stable and active at high temperatures (35-70
      degrees C). The fibrinolytic activity of undariase was strongly inhibited by
      phenylmethylsulfonyl fluoride (PMSF) and 4-(amidinophenyl) methanesulfonyl
      fluoride (APMSF). The K m and V max values for substrate S-2251 were determined
      as 6.15 mM and 90.91 mM/min/ml, respectively. Undariase resulted in clot lysis by
      directly cleaving alpha and beta chains of fibrin. Similarly, it preferentially
      acted on the Aalpha chain of fibrinogen followed by cleavage of the Bbeta chain.
      It significantly prolonged the PFA-100 closure times of citrated whole human
      blood. In addition, undariase delayed the coagulation time and increased
      activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin
      time (TT). Undariase exerted a significant protective effect against collagen
      plus epinephrine-induced pulmonary thromboembolism in mice. It prevented
      carrageenan-induced thrombus formation in the tail of mice. It also resulted in
      prolongation of APTT ex vivo. In conclusion, these results suggested a
      therapeutic potential of undariase for thrombosis. 

PMID- 24938823
TI  - Risk factors associated with severe and recurrent angioedema: an epidemic linked
      to ACE-inhibitors.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the etiology and risk factors for severe
      manifestation and recurrent episodes of angioedema; to evaluate efficacy of short
      term and long-term management strategies for angioedema among a high-risk
      population. STUDY DESIGN: Institutional review board-approved retrospective
      review of a large, urban population. METHODS: Data from 875 adult patients
      treated from January 2008 to December 2013 with the diagnosis of angioedema were
      obtained using the Clinical Looking Glass utility and review of medical records.
      Demographic and clinicopathologic risk factors were recorded. The major outcomes
      evaluated were hospital admission, need for airway intervention, and recurrent
      episodes of angioedema following the first presentation. Initial treatment
      strategy and follow-up recommendations were also recorded. RESULTS: The most
      common cause of angioedema was angiotensin converting enzyme inhibitor (ACEi)
      induced (496 [56.6%]). Significant risk factors for severe cases of angioedema
      included older age, Hispanic race, ACEi-induced angioedema type, American Society
      of Anesthesiologists class III or above, coexistent cardiopulmonary disease, and
      a positive smoking history. A total of 17.2% of patients experienced recurrent
      attacks of angioedema; of those patients, 25.9% were still taking an ACEi at
      subsequent presentation. Risk factors for recurrent episodes included older age,
      idiopathic angioedema type, and coexistent cardiopulmonary disease. Only 54.1% of
      patients who experienced ACEi-induced angioedema had electronic medical record
      documentation of these allergies. CONCLUSIONS: Knowledge of risk factors for
      severe and recurrent episodes of angioedema and improved education for both
      healthcare providers and patients, specifically related to ACEi use and allergy
      documentation, may significantly decrease the burden and morbidity of angioedema
      among high risk populations. LEVEL OF EVIDENCE: 2b.

PMID- 24938824
TI  - Early referral to specialist nephrology services for preventing the progression
      to end-stage kidney disease.
AB  - BACKGROUND: Early referral of patients with chronic kidney disease (CKD) is
      believed to help with interventions to address risk factors to slow down the rate
      of progression of kidney failure to end-stage kidney disease (ESKD) and the need
      for dialysis, hospitalisation and mortality. OBJECTIVES: We sought to evaluate
      the benefits (reduced hospitalisation and mortality; increased quality of life)
      and harms (increased hospitalisations and mortality, decreased quality of life)
      of early versus late referral to specialist nephrology services in CKD patients
      who are progressing to ESKD and RRT. In this review, referral is defined as the
      time period between first nephrology evaluation and initiation of dialysis; early
      referral is more than one to six months, whereas late referral is less than one
      to six months prior to starting dialysis. All-cause mortality and hospitalisation
      and quality of life were measured by the visual analogue scale and SF-36. SF-36
      and KDQoL are validated measurement instruments for kidney diseases. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library, 2012; Issue 1) which contains the Cochrane Renal Group's
      Specialised Register; MEDLINE (1966 to February 2012), EMBASE (1980 to February
      2012). Search terms were approved by the Trial Search Co-ordinator. SELECTION
      CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, prospective and
      retrospective longitudinal cohort studies were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed study quality and
      extracted data. Events relating to adverse effects were collected from the
      studies. MAIN RESULTS: No RCTs or quasi-RCTs were identified. There were 40
      longitudinal cohort studies providing data on 63,887 participants; 43,209 (68%)
      who were referred early and 20,678 (32%) referred late.Comparative mortality was
      higher in patients referred to specialist services late versus those referred
      early. Risk ratios (RR) for mortality reductions in patients referred early were
      evident at three months (RR 0.61, 95% CI 0.55 to 0.67; I2 = 84%) and remained at
      five years (RR 0.66, 95% CI 0.60 to 0.71; I2 = 87%). Initial hospitalisation was
      9.12 days shorter with early referral (95% CI -10.92 to -7.32 days; I2 = 82%)
      compared to late referral. Pooled analysis showed patients referred early were
      more likely than late referrals to initiate RRT with peritoneal dialysis (RR
      1.74, 95% CI 1.64 to 1.84; I2 = 92%).Patients referred early were less likely to
      receive temporary vascular access (RR 0.47, 95% CL 0.45 to 0.50; I2 = 97%) than
      those referred late. Patients referred early were more likely to receive
      permanent vascular access (RR 3.22, 95% CI 2.92 to 3.55; I2 = 97%). Systolic
      blood pressure (BP) was significantly lower in early versus late referrals (MD 
      3.09 mm Hg, 95% CI -5.23 to -0.95; I2 = 85%); diastolic BP was significantly
      lower in early versus late referrals (MD -1.64 mm Hg, 95% CI -2.77 to -0.51; I2 =
      82%). EPO use was significantly higher in those referred early (RR 2.92, 95% CI
      2.42 to 3.52; I2 = 0%). eGFR was higher in early referrals (MD 0.42 mL/min/1.73
      m2, 95% CI 0.28 to 0.56; I2 = 95%). Diabetes prevalence was similar in patients
      referred early and late (RR 1.05, 95% CI 0.96 to 1.15; I2 = 87%) as was ischaemic
      heart disease (RR 1.05, 95% CI 0.97 to 1.13; I2 = 74%), peripheral vascular
      disease (RR 0.99, 95% CI 0.84 to 1.17; I2 = 90%), and congestive heart failure
      (RR 1.00, 95% CI 0.86 to 1.15; I2 = 92%). Inability to walk was less prevalent in
      early referrals (RR 0.66, 95% CI 0.51 to 0.86). Prevalence of chronic obstructive
      pulmonary disease was similar in those referred early and late (RR 0.89, 95% CI
      0.70 to 1.14; I2 = 94%) as was cerebrovascular disease (RR 0.90, 95% CI 0.74 to
      1.11; I2 = 83%).The quality of the included studies was assessed as being low to
      moderate based on the Newcastle-Ottawa Scale. Slight differences in the
      definition of early versus late referral infer some risk of bias. Generally,
      heterogeneity in most of the analyses was high. AUTHORS' CONCLUSIONS: Our
      analysis showed reduced mortality and mortality and hospitalisation, better
      uptake of peritoneal dialysis and earlier placement of arteriovenous fistulae for
      patients with chronic kidney disease who were referred early to a nephrologist.
      Differences in mortality and hospitalisation data between the two groups were not
      explained by differences in prevalence of comorbid disease or serum phosphate.
      However, early referral was associated with better preparation and placement of
      dialysis access.

PMID- 24938825
TI  - Lived experiences of street-based female sex workers in Kathmandu: implications
      for health intervention strategies.
AB  - The lived experiences of women sex workers illustrate that sex work is frequently
      a manifestation of limited access to education, resources and jobs due to
      violence, oppression and patriarchy. However, some Nepalese sex workers
      reconstitute sex work as a viable form of work that provides food and shelter for
      their families and allows fulfillment of their duties as mothers. Through a
      culture-centred approach to research, which emphasis the voices of the
      marginalised and their own articulations of how marginalised spaces are
      negotiated, this paper offers an entry point to locating sex workers as active
      participants in their day-to-day lives. Thirty-five in-depth, semi-structured
      interviews were conducted with street-based female sex workers. Thematic analysis
      revealed the following three themes: (1) surviving through sex work, (2)
      financial security in sex work and (3) surviving sex work stigma. These findings
      have implications for health promotion involving members of this population.
      Lived experiences illustrate the need to move away from traditional, top-down,
      linear behaviour-change health campaigns to reconstitute health interventions
      within a participatory bottom-up approach that includes the voices of
      participants and is situated within their own context and needs. 

PMID- 24938826
TI  - Intestinal helminths of golden jackals and red foxes from Tunisia.
AB  - Forty wild canids including 31 golden jackals (Canis aureus Linne, 1758) and 9
      red foxes (Vulpes vulpes Linne, 1758) collected between 2008 and 2011 in the
      northeast, northwest and center of Tunisia were necropsied and examined for
      intestinal helminth parasites. All jackals and foxes were found infected with a
      prevalence rate of 95% for cestodes, 82.5% for nematodes and 7.5% for
      acanthocephalans. A total of twelve helminth species were recorded in red foxes:
      cestodes, Dipylidium caninum (55.6%), Diplopylidium noelleri (55.6%),
      Mesocestoides lineatus (55.6%), Mesocestoides litteratus (33%), Mesocestoides
      corti (22%); nematodes, Ancylostoma caninum (11%), Uncinaria stenocephala (44%),
      Spirura rytipleurites (11%), Trichuris vulpis (33%), Pterygodermatites affinis
      (67%), Oxynema linstowi (33%) and the acanthocephalan Macracanthorhynchus
      hirudinaceus (22%). The fifteen recovered helminth species in jackals were
      Echinococcus granulosus (9.7%), D. caninum (16%), D. noelleri (16%), M. lineatus
      (74%), M. litteratus (23%), M. corti (12.9%), Taenia pisiformis (3.2%), Taenia
      spp. (19%), Toxocara canis (16%), Toxascaris leonina (6.5%), A. caninum (9.7%),
      U. stenocephala (68%), P. affinis (6.5%), O. linstowi (3.2%) and
      Macracanthorhynchus hirudinaceus (3.2%). This is the first report on the presence
      of P. affinis, D. noelleri and O. linstowi in Tunisia. E. granulosus was found in
      young jackals, aged less than 4 years old, with a higher abundance in females
      (8.9 worms). M. lineatus presented the highest mean intensity of 231.86 and 108.8
      tapeworms respectively in jackals and foxes. Canids from the northwest region had
      the highest prevalence (77.5%) and highest intensity (243.7) of helminth species
      compared to those from the northeast and central areas. U. stenocephala and O.
      linstowi had the highest mean intensity for nematodes in both jackals and foxes
      at 14.3 and 88 worms respectively. 

PMID- 24938827
TI  - Evaluation of the inhibitory effects of miltefosine on the growth of Babesia and
      Theileria parasites.
AB  - Miltefosine, a membrane-active synthetic ether-lipid analogue, has
      antiproliferative and antiparasitic effects. In this study, the inhibitory
      effects of miltefosine were evaluated against three Babesia species and Theileria
      equi in vitro and against Babesia microti in mice. The drug showed significant
      growth inhibition from an initial parasitemia of 1% for Babesia bovis, Babesia
      bigemina, Babesia caballi, and T. equi with IC50 values of 25, 10.2, 10.4, and 99
      MUM, respectively. Complete inhibition was observed at 200 MUM of miltefosine on
      the third day of culture for the three Babesia species and 400 MUM on the fourth
      day for T. equi. Reverse-transcription PCR (RT-PCR) showed that miltefosine
      inhibited the transcription of choline-phosphate cytidylyltransferase in B.
      bovis. Miltefosine at a dose rate of 30 mg/kg resulted in a 71.7% inhibition of
      B. microti growth in BALB/c mice. Miltefosine might be used for drug therapy in
      babesiosis.

PMID- 24938828
TI  - Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning
      skills in a transgenic mice model of Alzheimer's disease.
AB  - Alzheimer disease (AD) is one of the most common forms of dementia in the
      elderly. Several reports have suggested neurotoxic effects of amyloid beta
      protein (Abeta) and role of oxidative stress in AD. Figs are rich in fiber,
      copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good
      source of proanthocyanidins and quercetin which demonstrate potent antioxidant
      properties. We studied the effect of dietary supplementation with 4% figs grown
      in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice)
      mice model for AD. We assessed spatial memory and learning ability, psychomotor
      coordination, and anxiety-related behavior in Tg and wild-type mice at the age of
      4 months and after 15 months using the Morris water maze test, rota-rod test,
      elevated plus maze test, and open-field test. Tg mice that were fed a control
      diet without figs showed significant memory deficits, increased anxiety-related
      behavior, and severe impairment in spatial, position discrimination learning
      ability, and motor coordination compared to the wild-type control mice on the
      same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our
      results suggest that dietary supplementation of figs may be useful for the
      improvement of cognitive and behavioral deficits in AD.

PMID- 24938829
TI  - Doctors should consult patients before imposing non-resuscitation notices unless
      it would cause harm, Court of Appeal rules.

PMID- 24938830
TI  - Quantitative susceptibility mapping using single-shot echo-planar imaging.
AB  - PURPOSE: To perform quantitative susceptibility mapping (QSM) in negligible
      acquisition time and apply it to measuring iron-rich subcortical gray matter.
      METHODS: Whole brain QSM was performed using single-shot gradient echo-planar
      imaging (EPI) in under 7 seconds on a standard 1.5 T system for imaging brain
      iron in subcortical gray matter. The method was compared to a standard 6-minute
      gradient recalled echo (GRE) QSM acquisition in healthy subjects. Region-of
      interest QSM measurements were compared between methods in six subcortical gray
      matter nuclei and two white matter territories. RESULTS: EPI-QSM provided similar
      mean susceptibility values to standard GRE-QSM in iron-rich subcortical gray
      matter regions, while providing greater than 50-fold scan time reduction.
      Blurring from the low spatial resolution and transverse relaxation decay of EPI
      affected edges but had negligible effect on whole subcortical nuclei
      measurements, which had a high correlation (R(2)  = 0.96) to estimated iron
      content. CONCLUSION: EPI-QSM can be performed in several seconds, which enables
      expansion of brain iron studies of subcortical gray matter to cases where time is
      limited and to existing MRI studies that already uses gradient echo EPI.

PMID- 24938831
TI  - A familial late-onset hereditary ataxia mimicking pontocerebellar hypoplasia
      caused by a novel TSEN54 mutation.
AB  - Pontocerebellar hypoplasia (PCH) comprises a rare group of neurodegenerative
      disorders with variable symptoms of cerebellar ataxia. Several gene mutations
      have been reported to be associated with different presentations of PCH. In the
      present study, an extended familial case of late-onset hereditary ataxia
      mimicking PCH in respect of clinical manifestation, neuroradiological findings
      and genetic analysis is described. By means of direct sequencing, a novel
      heterozygous mutation was found in the TSEN54 gene by c.254A > T(+) (p.E85V),
      which may be a new subtype of hereditary ataxia. However, this subtype was shown
      to exhibit late onset, differing from PCH with prenatal onset and predominantly
      affecting the growth of neurons.

PMID- 24938832
TI  - Determinants of change in subtropical tree diameter growth with ontogenetic
      stage.
AB  - We evaluated the degree to which relative growth rate (RGR) of saplings and large
      trees is related to seven functional traits that describe physiological behavior
      and soil environmental factors related to topography and fertility for 57
      subtropical tree species in Dinghushan, China. The mean values of functional
      traits and soil environmental factors for each species that were related to RGR
      varied with ontogenetic stage. Sapling RGR showed greater relationships with
      functional traits than large-tree RGR, whereas large-tree RGR was more associated
      with soil environment than was sapling RGR. The strongest single predictors of
      RGR were wood density for saplings and slope aspect for large trees. The stepwise
      regression model for large trees accounted for a larger proportion of variability
      (R(2) = 0.95) in RGR than the model for saplings (R(2) = 0.55). Functional
      diversity analysis revealed that the process of habitat filtering likely
      contributes to the substantial changes in regulation of RGR as communities
      transition from saplings to large trees.

PMID- 24938833
TI  - Litter identity mediates predator impacts on the functioning of an aquatic
      detritus-based food web.
AB  - During past decades, several mechanisms such as resource quality and habitat
      complexity have been proposed to explain variations in the strength of trophic
      cascades across ecosystems. In detritus-based headwater streams, litter
      accumulations constitute both a habitat and a resource for detritivorous
      macroinvertebrates. Because litter edibility (which promotes trophic cascades) is
      usually inversely correlated with its structural complexity (which weakens
      trophic cascades), there is a great scope for stronger trophic cascades in litter
      accumulations that are dominated by easily degradable litter species. However, it
      remains unclear how mixing contrasting litter species (conferring both habitat
      complexity and high quality resource) may influence top-down controls on
      communities and processes. In enclosures exposed in a second-order stream, we
      manipulated litter species composition by using two contrasting litter (alder and
      oak), and the presence-absence of a macroinvertebrate predator (Cordulegaster
      boltonii larvae), enabling it to effectively exert predation pressure, or not, on
      detritivores (consumptive versus non-consumptive predation effects). Leaf mass
      loss, detritivore biomass and community structure were mostly controlled
      independently by litter identity and mixing and by predator consumption. However,
      the strength of predator control was mediated by litter quality (stronger on
      alder), and to a lesser extent by litter mixing (weaker on mixed litter).
      Refractory litter such as oak leaves may contribute to the structural complexity
      of the habitat for stream macroinvertebrates, allowing the maintenance of
      detritivore communities even when strong predation pressure occurs. We suggest
      that considering the interaction between top-down and bottom-up factors is
      important when investigating their influence on natural communities and ecosystem
      processes in detritus-based ecosystems. 

PMID- 24938834
TI  - Ecological consequences of the expansion of N2-fixing plants in cold biomes.
AB  - Research in warm-climate biomes has shown that invasion by symbiotic dinitrogen
      (N2)-fixing plants can transform ecosystems in ways analogous to the
      transformations observed as a consequence of anthropogenic, atmospheric nitrogen
      (N) deposition: declines in biodiversity, soil acidification, and alterations to
      carbon and nutrient cycling, including increased N losses through nitrate
      leaching and emissions of the powerful greenhouse gas nitrous oxide (N2O). Here,
      we used literature review and case study approaches to assess the evidence for
      similar transformations in cold-climate ecosystems of the boreal, subarctic and
      upper montane-temperate life zones. Our assessment focuses on the plant genera
      Lupinus and Alnus, which have become invasive largely as a consequence of
      deliberate introductions and/or reduced land management. These cold biomes are
      commonly located in remote areas with low anthropogenic N inputs, and the
      environmental impacts of N2-fixer invasion appear to be as severe as those from
      anthropogenic N deposition in highly N polluted areas. Hence, inputs of N from N2
      fixation can affect ecosystems as dramatically or even more strongly than N
      inputs from atmospheric deposition, and biomes in cold climates represent no
      exception with regard to the risk of being invaded by N2-fixing species. In
      particular, the cold biomes studied here show both a strong potential to be
      transformed by N2-fixing plants and a rapid subsequent saturation in the
      ecosystem's capacity to retain N. Therefore, analogous to increases in N
      deposition, N2-fixing plant invasions must be deemed significant threats to
      biodiversity and to environmental quality. 

PMID- 24938835
TI  - Tissue-specific metabolite profiling of Cyperus rotundus L. rhizomes and (+)
      nootkatone quantitation by laser microdissection, ultra-high-performance liquid
      chromatography-quadrupole time-of-flight mass spectrometry, and gas
      chromatography-mass spectrometry techniques.
AB  - Cyperus rotundus L. is a plant species commonly found in both India and China.
      The caused destruction of this plant is of critical concern for agricultural
      produce. Nevertheless, it can serve as a potential source of the commercially
      important sesquiterpenoid (+)-nootkatone. The present work describes comparative
      metabolite profiling and (+)-nootkatone content determination in rhizome samples
      collected from these two countries. Laser dissected tissues, namely, the cortex,
      hypodermal fiber bundles, endodermis, amphivasal vascular bundles, and whole
      rhizomes were analyzed by ultra-high-performance liquid chromatography-quadrupole
      time-of-flight mass spectrometry (UHPLC-QTOF MS). Gas chromatography-mass
      spectrometry (GC-MS) analysis was used for profiling of essential oil
      constituents and quantitation of (+)-nootkatone. The content of (+)-nootkatone
      was found to be higher in samples from India (30.47 MUg/10 g) compared to samples
      from China (21.72 MUg/10 g). The method was validated as per International
      Conference on Harmonisation (ICH) guidelines (Q2 R1). The results from this study
      can be applied for quality control and efficient utilization of this terpenoid
      rich plant for several applications in food-based industries. 

PMID- 24938836
TI  - Memantine enhances recovery from stroke.
AB  - BACKGROUND AND PURPOSE: Stroke treatment is constrained by limited treatment
      windows and the clinical inefficacy of agents that showed preclinical promise.
      Yet animal and clinical data suggest considerable poststroke plasticity, which
      could allow treatment with recovery-modulating agents. Memantine is a well
      tolerated N-methyl-D-aspartate glutamate receptor antagonist in common use for
      Alzheimer disease. METHODS: Memantine, 30 mg/kg per day, or vehicle, was
      delivered chronically in drinking water beginning >2 hours after photothrombotic
      stroke. RESULTS: Although there was no difference in infarct size, behavior, or
      optical intrinsic signal maps in the first 7 days after stroke, mice treated
      chronically with memantine showed significant improvements in motor control,
      measured by cylinder test and grid-walking performance, compared with vehicle
      treated animals. Optical intrinsic signal revealed an increased area of forepaw
      sensory maps at 28 days after stroke. There was decreased reactive astrogliosis
      and increased vascular density around the infarcted cortex. Peri-infarct Western
      blots revealed increased brain-derived neurotrophic factor and phosphorylated
      tropomyosin-related kinase-B receptor expression. CONCLUSIONS: Our results
      suggest that memantine improves stroke outcomes in an apparently non
      neuroprotective manner involving increased brain-derived neurotrophic factor
      signaling, reduced reactive astrogliosis, and improved vascularization,
      associated with improved recovery of sensory and motor cortical function. The
      clinical availability and tolerability of memantine make it an attractive
      candidate for clinical translation.

PMID- 24938837
TI  - Modulation of mitochondrial function and autophagy mediates carnosine
      neuroprotection against ischemic brain damage.
AB  - BACKGROUND AND PURPOSE: Despite the rapidly increasing global burden of ischemic
      stroke, no therapeutic options for neuroprotection against stroke currently
      exist. Recent studies have shown that autophagy plays a key role in ischemic
      neuronal death, and treatments that target autophagy may represent a novel
      strategy in neuroprotection. We investigated whether autophagy is regulated by
      carnosine, an endogenous pleiotropic dipeptide that has robust neuroprotective
      activity against ischemic brain damage. METHODS: We examined the effect of
      carnosine on mitochondrial dysfunction and autophagic processes in rat focal
      ischemia and in neuronal cultures. RESULTS: Autophagic pathways such as reduction
      of phosphorylated mammalian target of rapamycin (mTOR)/p70S6K and the conversion
      of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II were enhanced
      in the ischemic brain. However, treatment with carnosine significantly attenuated
      autophagic signaling in the ischemic brain, with improvement of brain
      mitochondrial function and mitophagy signaling. The protective effect of
      carnosine against autophagy was also confirmed in primary cortical neurons.
      CONCLUSIONS: Taken together, our data suggest that the neuroprotective effect of
      carnosine is at least partially mediated by mitochondrial protection and
      attenuation of deleterious autophagic processes. Our findings shed new light on
      the mechanistic pathways that this exciting neuroprotective agent influences.

PMID- 24938838
TI  - Reprogramming the response to stroke by preconditioning.

PMID- 24938840
TI  - Visualization of local changes in vessel wall morphology and plaque progression
      in serial carotid artery magnetic resonance imaging.

PMID- 24938841
TI  - Impact of carotid atherosclerosis on the risk of adverse cardiac events in
      patients with and without coronary disease.
AB  - BACKGROUND AND PURPOSE: Carotid atherosclerosis (CA) is reportedly a strong
      predictor of imminent cardiac events even in the absence of established coronary
      artery disease (CAD). We examined the differential impact of CA on the risk of
      major adverse cardiovascular events in patients with and without CAD diagnosed
      angiographically. METHODS: We conducted a follow-up survey of 1391 patients who
      underwent clinically driven coronary angiography and a same-day carotid
      ultrasound and Doppler study. Definitions of CAD, CA, and carotid artery stenosis
      were in accordance with current practice guidelines. RESULTS: Of 1391 patients,
      angiographic CAD was present in 1105 (79%) patients. Mean and median follow-up
      was 1574 and 1702 days, respectively. Rates of the primary composite major
      adverse cardiovascular event end point were higher among patients with CAD
      compared with those without CAD (48% versus 20%; P<0.001), whereas the rates of
      all-cause mortality (10% versus 9%; P=0.81) and stroke (7% versus 5%; P=0.3) did
      not differ significantly between both groups. Carotid artery stenosis and CA were
      associated with an increased risk of the composite major adverse cardiovascular
      event end point among patients without CAD (hazard ratio=3.17 [95% confidence
      interval, 1.52-6.60]; P<0.01; and hazard ratio=1.69 [0.95-3.01]; P=0.07,
      respectively) though not in patients with CAD. Carotid artery stenosis was
      associated with an increased risk of all-cause mortality among patients without
      CAD (hazard ratio=2.93 [1.09-7.87]; P=0.03]) though not among those with CAD.
      CONCLUSIONS: CA and carotid artery stenosis are independent predictors of major
      adverse cardiovascular event in patients undergoing coronary angiography. The
      prognostic implications of carotid disease are imparted predominantly in patients
      without pre-existent CAD.

PMID- 24938842
TI  - Prehospital utility of rapid stroke evaluation using in-ambulance telemedicine: a
      pilot feasibility study.
AB  - BACKGROUND AND PURPOSE: Prehospital evaluation using telemedicine may accelerate
      acute stroke treatment with tissue-type plasminogen activator. We explored the
      feasibility and reliability of using telemedicine in the field and ambulance to
      help evaluate acute stroke patients. METHODS: Ten unique, scripted stroke
      scenarios, each conducted 4 times, were portrayed by trained actors retrieved and
      transported by Houston Fire Department emergency medical technicians to our
      stroke center. The vascular neurologists performed remote assessments in real
      time, obtaining clinical data points and National Institutes of Health (NIH)
      Stroke Scale, using the In-Touch RP-Xpress telemedicine device. Each scripted
      scenario was recorded for a subsequent evaluation by a second blinded vascular
      neurologist. Study feasibility was defined by the ability to conduct 80% of the
      sessions without major technological limitations. Reliability of video
      interpretation was defined by a 90% concordance between the data derived during
      the real-time sessions and those from the scripted scenarios. RESULTS: In 34 of
      40 (85%) scenarios, the teleconsultation was conducted without major technical
      complication. The absolute agreement for intraclass correlation was 0.997 (95%
      confidence interval, 0.992-0.999) for the NIH Stroke Scale obtained during the
      real-time sessions and 0.993 (95% confidence interval, 0.975-0.999) for the
      recorded sessions. Inter-rater agreement using kappa-statistics showed that for
      live-raters, 10 of 15 items on the NIH Stroke Scale showed excellent agreement
      and 5 of 15 showed moderate agreement. Matching of real-time assessments occurred
      for 88% (30/34) of NIH Stroke Scale scores by +/-2 points and 96% of the clinical
      information. CONCLUSIONS: Mobile telemedicine is reliable and feasible in
      assessing actors simulating acute stroke in the prehospital setting.

PMID- 24938843
TI  - Diagnostic yield of pelvic magnetic resonance venography in patients with
      cryptogenic stroke and patent foramen ovale.
AB  - BACKGROUND AND PURPOSE: Paradoxical embolization is frequently posited as a
      mechanism of ischemic stroke in patients with patent foramen ovale. Several
      studies have suggested that the deep lower extremity and pelvic veins might be an
      embolic source in cryptogenic stroke (CS) patients with patent foramen ovale.
      METHODS: Consecutive adult patients with ischemic stroke or transient ischemic
      attack and a patent foramen ovale who underwent pelvic magnetic resonance
      venography as part of an inpatient diagnostic evaluation were included in this
      single-center retrospective observational study to determine pelvic and lower
      extremity (LE) deep venous thrombosis (DVT) prevalence in CS versus non-CS stroke
      subtypes. RESULTS: Of 131 patients who met inclusion criteria, 126 (96.2%) also
      had LE duplex ultrasound data. DVT prevalence overall was 7.6% (95% confidence
      interval, 4.1-13.6), pelvic DVT 1.5% (95% confidence interval, 0.1-5.8), and LE
      DVT 7.1% (95% confidence interval, 3.6-13.2). One patient with a pelvic DVT also
      had a LE DVT. Comparing patients with CS (n=98) with non-CS subtypes (n=33),
      there was no significant difference in the prevalence of pelvic DVT (2.1% versus
      0%, P=1), LE DVT (6.2% versus 10.3%, P=0.43), or any DVT (7.2% versus 9.1%,
      P=0.71). CONCLUSIONS: Among patients with ischemic stroke/transient ischemic
      attack and patent foramen ovale, the majority of detected DVTs were in LE veins
      rather than the pelvic veins and did not differ by stroke subtype. The routine
      inclusion of pelvic magnetic resonance venography in the diagnostic evaluation of
      CS warrants further prospective investigation.

PMID- 24938839
TI  - Cell-culture models of the blood-brain barrier.

PMID- 24938844
TI  - Gene expression profiling reveals distinct molecular signatures associated with
      the rupture of intracranial aneurysm.
AB  - BACKGROUND AND PURPOSE: The rupture of intracranial aneurysm (IA) causes
      subarachnoid hemorrhage associated with high morbidity and mortality. We compared
      gene expression profiles in aneurysmal domes between unruptured IAs and ruptured
      IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA.
      METHODS: We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10
      superficial temporal arteries with the Agilent microarrays. To explore biological
      heterogeneity of IAs, we classified the samples into subgroups showing similar
      gene expression patterns, using clustering methods. RESULTS: The clustering
      analysis identified 4 groups: superficial temporal arteries and unruptured IAs
      were aggregated into their own clusters, whereas RIAs segregated into 2 distinct
      subgroups (early and late RIAs). Comparing gene expression levels between early
      RIAs and unruptured IAs, we identified 430 upregulated and 617 downregulated
      genes in early RIAs. The upregulated genes were associated with inflammatory and
      immune responses and phagocytosis including S100/calgranulin genes (S100A8,
      S100A9, and S100A12). The downregulated genes suggest mechanical weakness of
      aneurysm walls. The expressions of Kruppel-like family of transcription factors
      (KLF2, KLF12, and KLF15), which were anti-inflammatory regulators, and CDKN2A,
      which was located on chromosome 9p21 that was the most consistently replicated
      locus in genome-wide association studies of IA, were also downregulated.
      CONCLUSIONS: We demonstrate that gene expression patterns of RIAs were different
      according to the age of patients. The results suggest that macrophage-mediated
      inflammation is a key biological pathway for IA rupture. The identified genes can
      be good candidates for molecular markers of rupture-prone IAs and therapeutic
      targets.

PMID- 24938845
TI  - Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in
      patients with intracranial stenosis.
AB  - BACKGROUND AND PURPOSE: A promising method for identifying hemodynamic impairment
      that may serve as a biomarker for stroke risk in patients with intracranial
      stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here,
      abilities to measure CVR safely in the clinic using hypercarbic hyperoxic
      (carbogen) gas challenges, which increase oxygen delivery to tissue, are
      investigated. METHODS: In sequence with structural and angiographic imaging,
      blood oxygenation level-dependent carbogen-induced CVR scans were performed in
      patients with symptomatic intracranial stenosis (n=92) and control (n=10)
      volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow
      weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified
      for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic
      normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and
      blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57),
      (3) carbogen CVR and clinical measures of disease in patients with asymmetrical
      intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR
      scan and immediate and longer-term complications (n=92). RESULTS: Noninvasive
      blood oxygenation level-dependent carbogen-induced CVR values correlate with (1)
      lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2)
      carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis
      (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in
      atherosclerotic and moyamoya patients after appropriate processing. No immediate
      stroke-related complications were reported in response to carbogen
      administration; longer-term neurological events fell within the range for
      expected events in this patient population. CONCLUSIONS: Carbogen-induced CVR
      elicited no added adverse events and provided a surrogate marker of
      cerebrovascular reserve consistent with intracranial vasculopathy.

PMID- 24938846
TI  - Socioeconomic inequalities in stroke incidence among migrant groups: analysis of
      nationwide data.
AB  - BACKGROUND AND PURPOSE: Low socioeconomic status has been linked to high
      incidence of stroke in industrialized countries; therefore, reducing
      socioeconomic disparities is an important goal of health policy. The evidence on
      migrant groups is, however, limited and inconsistent. We assessed socioeconomic
      inequalities in relation to stroke incidence among major ethnic groups in the
      Netherlands. METHODS: A nationwide register-based cohort study was conducted (n=2
      397 446) between January 1, 1998, and December 31, 2010, among ethnic Dutch and
      ethnic minority groups. Standardized disposable household income was used as a
      measure of socioeconomic position. RESULTS: Among ethnic Dutch, the incidence of
      stroke was higher in the low-income group than in the high-income group (adjusted
      hazard ratio, 1.18; 95% confidence interval, 1.16-1.20). Similar socioeconomic
      inequalities in stroke incidence were found among Surinamese (1.36; 1.17-1.58),
      Indonesians (1.15; 1.03-1.28), Moroccans (1.54; 0.97-2.43), Turkish (1.19; 0.97
      1.46), and to a lesser extent among Antilleans (1.24; 0.84-1.84). When compared
      with ethnic Dutch, the incidence of stroke was lower in Moroccans, similar in
      Turkish, but higher in Surinamese among all income groups. The incidence of
      stroke was higher in Indonesian low- and high-income groups than in their ethnic
      Dutch counterparts. Among Antilleans, the risk of stroke was higher than ethnic
      Dutch but only in the low-income group. CONCLUSIONS: Our findings reveal
      socioeconomic inequalities in stroke incidence among all ethnic groups. Reduction
      of socioeconomic inequalities in stroke incidence among all ethnic groups may
      lead to a major public health improvement for all. Policy measures tackling
      socioeconomic inequalities should take into account the increased risk of stroke
      among ethnic minority populations.

PMID- 24938847
TI  - Value of eye movement examination in aiding precise localization in stroke.

PMID- 24938848
TI  - Predictive value of newly detected atrial fibrillation paroxysms in patients with
      acute ischemic stroke, for atrial fibrillation after 90 days.
AB  - BACKGROUND AND PURPOSE: Extended cardiac monitoring immediately after acute
      ischemic stroke (AIS) increases paroxysmal atrial fibrillation (PAF) detection,
      but its reliability for detection or exclusion of longer term paroxysmal PAF is
      unknown. We evaluated the positive and negative predictive value (PPV and NPV) of
      AF detection early after AIS, for PAF confirmation 90 days later. METHODS: We
      investigated 49 patients within 7 days of AIS for PAF according to current
      guidelines; 23 patients received 7 days of additional noninvasive cardiac event
      monitoring with an R-test device early after their stroke (ISRCTN 97412358).
      Ninety days after AIS, everyone underwent 7 days of cardiac event monitoring. We
      calculated the PPV and NPV of immediate PAF detection through extended cardiac
      event monitoring and through any investigative modality, for the presence of PAF
      on the 90-day event monitor. RESULTS: PAF detected by a 7-day event monitor
      within 2 weeks of AIS had a PPV of 100% (95% confidence interval, 72%-100%) for
      PAF confirmation after 90 days. NPV after 7 days of event monitoring was 64% (95%
      confidence interval, 35%-87%). PAF detected early through any modality had a PPV
      of 100% (95% confidence interval, 76%-100%). However, the NPV in the absence of R
      test monitoring was only 42% (95% confidence interval, 28%-58%). CONCLUSIONS: AF
      detection through any means immediately after stroke holds strong PPV for
      confirmation after 90 days, justifying treatment decisions on early monitoring
      alone. However, failure to identify AF through early monitoring has only modest
      NPV even after 7 days of monitoring; repeated investigation is desirable.

PMID- 24938849
TI  - The relationship between years of cocaine use and brain activation to cocaine and
      response inhibition cues.
AB  - AIMS: Functional magnetic resonance imaging research has attempted to elucidate
      the neurobehavioral underpinnings of cocaine dependence by evaluating differences
      in brain activation to cocaine and response inhibition cues between cocaine
      dependent individuals and controls. This study investigated associations between
      task-related brain activation and cocaine use characteristics. DESIGN: Cross
      sectional. SETTING: The Center for Biomedical Imaging at the Medical University
      of South Carolina, USA. PARTICIPANTS: Fifty-one cocaine users (41 dependent).
      MEASUREMENTS: Brain activation to cocaine-cue exposure and Go No-Go tasks in six
      a priori selected brain regions of interest and cocaine use characteristics (i.e.
      cocaine dependence status, years of cocaine use, cocaine use in the past 90 days)
      assessed via standardized interviews. FINDINGS: Participants demonstrated
      elevated activation to cocaine (bilateral ventral striatum, dorsal caudate,
      amygdala) and response inhibition (bilateral anterior cingulate, insula, inferior
      frontal gyrus) cues in all hypothesized brain regions. Years of cocaine use was
      associated with task-related brain activation, with more years of cocaine use
      associated with greater activation to cocaine cues in right (F = 7.97, P = 0.01)
      and left (F = 5.47, P = 0.02) ventral striatum and greater activation to response
      inhibition cues in left insula (F = 5.10, P = 0.03) and inferior frontal gyrus (F
      = 4.12, P = 0.05) controlling for age, cocaine dependence status and cocaine use
      in the past 90 days. CONCLUSIONS: Years of cocaine use may be more centrally
      related to cocaine cue and response inhibition brain activation than cocaine
      dependence diagnosis or amount of recent use.

PMID- 24938851
TI  - The spreading worldwide obesity epidemic.

PMID- 24938852
TI  - Blast-Induced tinnitus and spontaneous firing changes in the rat dorsal cochlear
      nucleus.
AB  - Exposure to high-pressure blast shock waves is known to cause tinnitus. Although
      the underlying mechanisms may involve damage to structures in the ear and/or
      direct brain impact, which triggers a cascade of neuroplastic changes in both
      auditory and nonauditory centers, it remains unclear how the induced
      neuroplasticity manifests neurophysiologically. This study investigates the
      influence of blast exposure on spontaneous firing rates (SFRs) in the dorsal
      cochlear nucleus (DCN) and its time course in rats with blast-induced tinnitus.
      Each rat was exposed to a single blast at 22 psi. Behavioral evidence of tinnitus
      was measured by using a gap-detection acoustic startle-reflex paradigm. SFRs were
      measured 1 day, 1 month, and 3 months after blast exposure. The results showed
      that nine rats with blast-induced tinnitus and hearing loss developed
      hyperactivity immediately and that the induced hyperactivity persisted in six
      rats with tinnitus at 1 month after blast exposure. At 3 months after blast
      exposure, however, the induced hyperactivity of four rats with tinnitus
      transitioned to hypoactivity. In addition, the 20-30-kHz, and >30-kHz regions in
      the DCN of rats with and without blast-induced tinnitus were more affected than
      other frequency regions at different recovery time points after blast exposure.
      These results demonstrate that the neural mechanisms underlying blast-induced
      tinnitus are substantially different from those underlying noise-induced
      tinnitus.

PMID- 24938850
TI  - Population pharmacokinetic study of gentamicin in a large cohort of premature and
      term neonates.
AB  - AIM: This study aims to investigate the clinical and demographic factors
      influencing gentamicin pharmacokinetics in a large cohort of unselected premature
      and term newborns and to evaluate optimal regimens in this population. METHODS:
      All gentamicin concentration data, along with clinical and demographic
      characteristics, were retrieved from medical charts in a Neonatal Intensive Care
      Unit over 5 years within the frame of a routine therapeutic drug monitoring
      programme. Data were described using non-linear mixed-effects regression analysis
      ( nonmem(r)). RESULTS: A total of 3039 gentamicin concentrations collected in 994
      preterm and 455 term newborns were included in the analysis. A two compartment
      model best characterized gentamicin disposition. The average parameter estimates,
      for a median body weight of 2170 g, were clearance (CL) 0.089 l h(-1) (CV 28%),
      central volume of distribution (Vc ) 0.908 l (CV 18%), intercompartmental
      clearance (Q) 0.157 l h(-1) and peripheral volume of distribution (Vp ) 0.560 l.
      Body weight, gestational age and post-natal age positively influenced CL.
      Dopamine co-administration had a significant negative effect on CL, whereas the
      influence of indomethacin and furosemide was not significant. Both body weight
      and gestational age significantly influenced Vc . Model-based simulations
      confirmed that, compared with term neonates, preterm infants need higher doses,
      superior to 4 mg kg(-1) , at extended intervals to achieve adequate
      concentrations. CONCLUSIONS: This observational study conducted in a large cohort
      of newborns confirms the importance of body weight and gestational age for dosage
      adjustment. The model will serve to set up dosing recommendations and elaborate a
      Bayesian tool for dosage individualization based on concentration monitoring.

PMID- 24938853
TI  - Light-dependent gravitropism and negative phototropism of inflorescence stems in
      a dominant Aux/IAA mutant of Arabidopsis thaliana, axr2.
AB  - Gravitropism and phototropism of the primary inflorescence stems were examined in
      a dominant Aux/IAA mutant of Arabidopsis, axr2/iaa7, which did not display either
      tropism in hypocotyls. axr2-1 stems completely lacked gravitropism in the dark
      but slowly regained it in light condition. Though wild-type stems showed positive
      phototropism, axr2 stems displayed negative phototropism with essentially the
      same light fluence-response curve as the wild type (WT). Application of 1
      naphthaleneacetic acid-containing lanolin to the stem tips enhanced the positive
      phototropism of WT, and reduced the negative phototropism of axr2. Decapitation
      of stems caused a small negative phototropism in WT, but did not affect the
      negative phototropism of axr2. p-glycoprotein 1 (pgp1) pgp19 double mutants
      showed no phototropism, while decapitated double mutants exhibited negative
      phototropism. Expression of auxin-responsive IAA14/SLR, IAA19/MSG2 and SAUR50
      genes was reduced in axr2 and pgp1 pgp19 stems relative to that of WT. These
      suggest that the phototropic response of stem is proportional to the auxin supply
      from the shoot apex, and that negative phototropism may be a basal response to
      unilateral blue-light irradiation when the levels of auxin or auxin signaling are
      reduced to the minimal level in the primary stems. In contrast, all of these
      treatments reduced or did not affect gravitropism in wild-type or axr2 stems.
      Tropic responses of the transgenic lines that expressed axr2-1 protein by the
      endodermis-specific promoter suggest that AXR2-dependent auxin response in the
      endodermis plays a more crucial role in gravitropism than in phototropism in
      stems but no significant roles in either tropism in hypocotyls. 

PMID- 24938856
TI  - Large esophageal schwannoma mimicking thyroid tumor with egg-shell calcification
      on preoperative ultrasonography.
AB  - Schwannoma tumors in esophagus are extremely rare and clinically present as
      dysphagia in most reported cases. Because of their rarity and need for
      histopathological confirmation using immunohistochemistry, an erroneous
      diagnostic and therapeutic approach can be adopted. A 36-year-old woman presented
      at the hospital with complaints of an anterior neck mass. On ultrasonography, a
      large left thyroid mass with egg-shell calcification was suspected. However, the
      thyroid surgeon found that it was not a thyroid tumor. An incision biopsy was
      performed for histopathological analysis, which revealed a schwannoma. Then,
      salivary leakage occurred through the cervical incision site, suggesting that the
      incisional biopsy had caused esophageal perforation. She was transferred to our
      department and underwent emergency surgery. We successfully resected the tumor
      and controlled the infection without any further injury to the esophagus,
      although it was a revision surgery and the wound was greatly infected. We believe
      that it is important to always keep in mind that an atypical presentation of
      esophageal schwannoma may lead to the development of, for example, a large nodule
      in the left thyroid gland involving the esophagus.

PMID- 24938855
TI  - Neurological adverse events in patients receiving anti-TNF therapy: a prospective
      imaging and electrophysiological study.
AB  - INTRODUCTION: The aim was to investigate the frequency of neurological adverse
      events in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA)
      treated with tumor necrosis factor (TNF) alpha antagonists. METHODS: Seventy
      seven patients eligible for anti-TNFalpha therapy were evaluated. There were 36
      patients with RA, 41 with SpA [24 psoriatic arthritis (PsA) and 17 with
      ankylosing spondylitis (AS)]. All patients had a complete physical and
      neurological examination. Brain and cervical spine magnetic resonance imaging
      (MRI) and neurophysiological tests were performed in all patients before the
      initiation of anti-TNFalpha therapy and after a mean of 18 months or when
      clinical symptoms and signs indicated a neurological disease. Exclusion criteria
      included hypertension, diabetes mellitus, dyslipidemia, heart arrhythmias,
      atherothrombotic events, vitamin B12 and iron deficiency, head and neck trauma
      and neurological surgeries. RESULTS: Two patients did not receive anti-TNFalpha
      therapy because brain MRIs at baseline revealed lesions compatible with
      demyelinating diseases. Thus, 75 patients received anti-TNFalpha (38 infliximab,
      19 adalimumab and 18 etanercept). Three patients developed neurological adverse
      events. A 35-year-old man with PsA after 8 months of infliximab therapy presented
      with paresis of the left facial nerve and brain MRI showed demyelinating lesions.
      Infliximab was discontinued and he was treated with pulses of corticosteroids
      recovering completely after two months. The second patient was a 45-year-old
      woman with RA who after 6 months of adalimumab therapy presented with optic
      neuritis. The third patient was a 50-year-old woman with AS, whom after 25 months
      of infliximab therapy, presented with tingling and numbness of the lower
      extremities and neurophysiological tests revealed peripheral neuropathy. In both
      patients anti-TNF were discontinued and they improved without treatment after 2
      months. The rest of our patients showed no symptoms and MRIs showed no
      abnormalities. The estimated rate of neurological adverse events in patients
      treated with anti-TNF therapy is 4% (3/75). CONCLUSIONS: Neurological adverse
      events after anti-TNFalpha therapy were observed in our patient. Brain MRI and
      neurophysiological tests are essential tools to discriminate neurological
      diseases.

PMID- 24938857
TI  - Predictive factors for intraoperative excessive bleeding in Graves' disease.
AB  - BACKGROUND: In Graves' disease, because a thyroid tends to have extreme
      vascularity, the amount of intraoperative blood loss (AIOBL) becomes significant
      in some cases. We sought to elucidate the predictive factors of the AIOBL.
      METHODS: A total of 197 patients underwent thyroidectomy for Graves' disease
      between 2002 and 2012. We evaluated clinical factors that would be potentially
      related to AIOBL retrospectively. RESULTS: The median period between disease
      onset and surgery was 16 months (range: 1-480 months). Conventional surgery was
      performed in 125 patients, whereas video-assisted surgery was performed in 72
      patients. Subtotal and near-total/total thyroidectomies were performed in 137
      patients and 60 patients, respectively. The median weight of the thyroid was 45 g
      (range: 7.3-480.0 g). Univariate analysis revealed that the strongest correlation
      of AIOBL was noted with the weight of thyroid (p < 0.001). Additionally, AIOBL
      was correlated positively with the period between disease onset and surgery (p <
      0.001) and negatively with preoperative free T4 (p < 0.01). Multivariate analysis
      showed that only the weight of the thyroid was independently correlated with
      AIOBL (p < 0.001). Four patients (2.0%) needed blood transfusion, including two
      requiring autotransfusion, whose thyroids were all weighing in excess of 200 g.
      The amount of drainage during the initial 6 hours and days until drain removal
      was correlated positively with AIOBL (p < 0.001, each). Occurrences of
      postoperative complications, such as recurrent laryngeal nerve palsy or
      hypoparathyroidism, and postoperative hospital stay were not correlated with
      AIOBL. CONCLUSION: A huge goiter presented as a predictive factor for excessive
      bleeding during surgery for Graves' disease, and preparation for blood
      transfusion should be considered in cases where thyroids weigh more than 200 g.

PMID- 24938858
TI  - Intramedullary schwannoma of conus medullaris with syringomyelia.
AB  - Intramedullary schwannomas of the spinal cord are rare tumors. They are most
      commonly observed in the cervical region; however, few have been described in the
      conus medullaris. The association of intramedullary schwannomas with
      syringomyelia is also rare. In this report, we present a case of intramedullary
      schwannoma of the conus medullaris with syringomyelia, which was treated
      surgically.

PMID- 24938859
TI  - Retrograde jejunogastric intussusception: A case report and review of the
      literature.
AB  - Retrograde jejunogastric intussusception (JGI) is a rare but potentially fatal
      complication after previous gastrectomy or gastric bypass surgery. Because of the
      prevalence of bariatric surgery, the number of cases of postoperative
      intussusception has increased markedly. Here, we present the case of a patient
      with retrograde jejunogastric intussusception, having a previous history of
      subtotal gastrectomy and gastrojejunostomy for peptic ulcer disease. Correct
      preoperative diagnosis was made by plain abdominal film, upper gastrointestinal
      series, computed tomographic scan, and esophagogastroduodenoscopy. The diagnosis
      was confirmed by laparoscopic examination.

PMID- 24938860
TI  - New regenerative approach to atrophic rhinitis using autologous lipoaspirate
      transfer and platelet-rich plasma in five patients: Our Experience.

PMID- 24938862
TI  - Metal-free annulation of arenes with 2-aminopyridine derivatives: the methyl
      group as a traceless non-chelating directing group.
AB  - A novel annulation reaction between 2-aminopyridine derivatives and arenes under
      metal-free conditions is described. The presented intermolecular transformation
      provided straightforward access to the important pyrido[1,2-a]benzimidazole
      scaffold under mild reaction conditions. The unprecedented application of the
      methyl group of methylbenzenes as a traceless, non-chelating, and highly
      regioselective directing group is reported. 

PMID- 24938861
TI  - Microbial aetiology, outcomes, and costs of hospitalisation for community
      acquired pneumonia; an observational analysis.
AB  - BACKGROUND: The aim of this study was to investigate the clinical outcome and
      especially costs of hospitalisation for community-acquired pneumonia (CAP) in
      relation to microbial aetiology. This knowledge is indispensable to estimate cost
      effectiveness of new strategies aiming to prevent and/or improve clinical outcome
      of CAP. METHODS: We performed our observational analysis in a cohort of 505
      patients hospitalised with confirmed CAP between 2004 and 2010. Hospital
      administrative databases were extracted for all resource utilisation on a patient
      level. Resource items were grouped in seven categories: general ward nursing,
      nursing on ICU, clinical chemistry laboratory tests, microbiology exams,
      radiology exams, medication drugs, and other.linear regression analyses were
      conducted to identify variables predicting costs of hospitalisation for CAP.
      RESULTS: Streptococcus pneumoniae was the most identified causative pathogen
      (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%).
      Overall median length of hospital stay was 8.5 days, in-hospital mortality rate
      was 4.8%.Total median hospital costs per patient were ?3,899 (IQR 2,911-5,684).
      General ward nursing costs represented the largest share (57%), followed by
      nursing on the intensive care unit (16%) and diagnostic microbiological tests
      (9%). In multivariate regression analysis, class IV-V Pneumonia Severity Index
      (indicative for severe disease), Staphylococcus aureus, or Streptococcus
      pneumonia as causative pathogen, were independent cost driving factors. Coxiella
      burnetii was a cost-limiting factor. CONCLUSIONS: Median costs of hospitalisation
      for CAP are almost ?4,000 per patient. Nursing costs are the main cause of these
      costs.. Apart from prevention, low-cost interventions aimed at reducing length of
      hospital stay therefore will most likely be cost-effective.

PMID- 24938863
TI  - In situ study of the growth of two-dimensional palladium dendritic nanostructures
      using liquid-cell electron microscopy.
AB  - We investigated the growth of two-dimensional (2D) palladium dendritic
      nanostructures (DNSs) using in situ liquid-cell transmission electron microscopy
      (TEM). Detailed in situ and ex situ high-resolution scanning TEM (S/TEM)
      characterization and fractal dimension analyses reveal that the diffusion-limited
      aggregation and direct atomic deposition are responsible for the growth of
      palladium dendritic nanostructures. 

PMID- 24938864
TI  - Children's psychosocial wellbeing in the context of HIV/AIDS and poverty: a
      comparative investigation of orphaned and non-orphaned children living in South
      Africa.
AB  - BACKGROUND: Recent studies have questioned whether orphanhood is primarily
      associated with key dimensions of psycho-social wellbeing in children living in
      circumstances of material deprivation and high prevalence of HIV and AIDS.
      METHODS: This study uses cross-sectional data from a longitudinal study conducted
      between 2004-2007 to examine the psychosocial well-being of orphans and non
      orphans in the Amajuba District of KwaZulu-Natal, South Africa. Psychosocial
      wellbeing included an assessment of orphans' and non orphans' level of anxiety
      and depression, affability and resilience. Stratified cluster sampling, based on
      both school and age, was used to construct a cohort of recent orphans and non
      orphans and their households, randomly selected from schools. RESULTS: Levels of
      anxiety and depression, affability and resilience did not differ significantly
      between orphans and non-orphans, nor did salient household, poverty and caregiver
      characteristics vary substantially amongst orphans and non-orphans. Multivariate
      analyses indicated that children's psychosocial outcomes, when controlling for
      orphan status and related demographic variables were more strongly influenced by
      household composition/size, living above or below the poverty threshold and
      factors associated with the caregiver-child relationship and caregiver health.
      CONCLUSIONS: The results muster additional evidence for moving beyond narrow
      definitions of vulnerability associated exclusively with orphanhood to consider
      the multitude of material, social and relational factors affecting the psycho
      social well-being of children in general who are living in circumstances of
      poverty and HIV and AIDS.

PMID- 24938865
TI  - Multi-view singular value decomposition for disease subtyping and genetic
      associations.
AB  - BACKGROUND: Accurate classification of patients with a complex disease into
      subtypes has important implications for medicine and healthcare. Using more
      homogeneous disease subtypes in genetic association analysis will facilitate the
      detection of new genetic variants that are not detectible using the non
      differentiated disease phenotype. Subtype differentiation can also improve
      diagnostic classification, which can in turn inform clinical decision making and
      treatment matching. Currently, the most sophisticated methods for disease
      subtyping perform cluster analysis using patients' clinical features. Without
      guidance from genetic information, the resultant subtypes are likely to be
      suboptimal and efforts at genetic association may fail. RESULTS: We propose a
      multi-view matrix decomposition approach that integrates clinical features with
      genetic markers to detect confirmatory evidence for a disease subtype. This
      approach groups patients into clusters that are consistent between the clinical
      and genetic dimensions of data; it simultaneously identifies the clinical
      features that define the subtype and the genotypes associated with the subtype. A
      simulation study validated the proposed approach, showing that it identified
      hypothesized subtypes and associated features. In comparison to the latest
      biclustering and multi-view data analytics using real-life disease data, the
      proposed approach identified clinical subtypes of a disease that differed from
      each other more significantly in the genetic markers, thus demonstrating the
      superior performance of the proposed approach. CONCLUSIONS: The proposed
      algorithm is an effective and superior alternative to the disease subtyping
      methods employed to date. Integration of phenotypic features with genetic markers
      in the subtyping analysis is a promising approach to identify concurrently
      disease subtypes and their genetic associations.

PMID- 24938866
TI  - Early optimal nutrition improves neurodevelopmental outcomes for very preterm
      infants.
AB  - Recent advances in perinatal and neonatal intensive care have resulted in
      significant improvements in the survival of preterm extremely low-birthweight
      (PELBW) infants; however, extrauterine growth restriction (EUGR) and
      undernutrition occur frequently during hospitalization and are associated with
      adverse outcomes, including bronchopulmonary dysplasia, sepsis, and
      neurodevelopmental impairment. Early optimal parenteral nutrition with adequate
      amino acids and lipids, especially long-chain polyunsaturated fatty acids, has
      been shown to decrease the incidence of EUGR, bronchopulmonary dysplasia,
      necrotizing enterocolitis, sepsis, and retinopathy of prematurity in animal
      models and clinical trials. In PELBW infants, breast milk and probiotics have
      been shown to reduce the incidence of necrotizing enterocolitis, and lactoferrin
      has been demonstrated to prevent late-onset sepsis. Thus, early administration of
      optimal postnatal parenteral and enteral nutrients can help prevent
      neurodevelopmental impairment caused by EUGR, necrotizing enterocolitis, sepsis,
      bronchopulmonary dysplasia, and retinopathy of prematurity, and recent evidence
      indicates such treatment is feasible. 

PMID- 24938867
TI  - Organic semiconductor density of states controls the energy level alignment at
      electrode interfaces.
AB  - Minimizing charge carrier injection barriers and extraction losses at interfaces
      between organic semiconductors and metallic electrodes is critical for optimizing
      the performance of organic (opto-) electronic devices. Here, we implement a
      detailed electrostatic model, capable of reproducing the alignment between the
      electrode Fermi energy and the transport states in the organic semiconductor both
      qualitatively and quantitatively. Covering the full phenomenological range of
      interfacial energy level alignment regimes within a single, consistent framework
      and continuously connecting the limiting cases described by previously proposed
      models allows us to resolve conflicting views in the literature. Our results
      highlight the density of states in the organic semiconductor as a key factor. Its
      shape and, in particular, the energy distribution of electronic states tailing
      into the fundamental gap is found to determine both the minimum value of
      practically achievable injection barriers as well as their spatial profile,
      ranging from abrupt interface dipoles to extended band-bending regions. 

PMID- 24938869
TI  - Incidence of delirium in children with cancer.
AB  - There are limited data on the incidence of delirium in children with cancer. We
      performed a retrospective chart review of all pediatric oncology admissions over
      a 1 year period to determine the incidence of delirium in this population. We
      identified seven patients with delirium (10% incidence). Delirium is associated
      with significant morbidity and mortality, and is likely under-recognized in this
      population. Improved diagnosis and treatment of delirium may improve outcomes in
      children with cancer.

PMID- 24938868
TI  - Protective role of TNF-alpha, IL-10 and IL-2 in mice infected with the Oshima
      strain of Tick-borne encephalitis virus.
AB  - Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease.
      Here, we investigated the roles of the TNF-alpha, IL-10 and other cytokines in
      appropriate KO mice following infection with Oshima and Sofjin strains of TBEV.
      Following infection with the Oshima strain, mortality rates were significantly
      increased in TNF-alpha KO and IL-10 KO mice compared with wild type (WT) mice.
      These results suggested that TNF-alpha and IL-10 play protective roles against
      fatal infection due to Oshima strain infection. However, viral loads and
      proinflammatory cytokine levels in the brain of TNF-alpha KO andIL-10 KO mice
      were not significantly different compared with those of WT mice. On the other
      hand, all WT, TNF-alpha KO and IL-10 KO mice died following infection with Sofjin
      strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA
      level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice
      showed significantly increased level of IL-2 compared with mock-infected mice.
      From these results, we suggest that TNF-alpha, IL-10 and IL-2 are key factors for
      disease remission from fatal encephalitis due to infection with Oshima strain of
      TBEV. 

PMID- 24938870
TI  - Effect of Substance P on type II alveolar epithelial cells exposed to hyperoxia
      and its regulation of the Sonic hedgehog signaling pathway.
AB  - Oxidative stress injury and cell death in alveolar epithelial cells may lead to
      abnormal repair, further resulting in acute and chronic pulmonary diseases.
      Substance P (SP) has multiple biological activities. The Sonic hedgehog (SHH)
      pathway is important in lung development and decreasing epithelial injury. To
      investigate the effects of SP on alveolar epithelial type II cells (AEC IIs), AEC
      IIs were exposed to 95% oxygen and the SHH signaling pathway was examined.
      Primary AEC IIs were isolated and purified from premature rats. The cells were
      divided into four groups: The air (21% oxygen) group, hyperoxia (95% oxygen)
      group, hyperoxia + SP group and hyperoxia + SP + L703.606 group. The activity of
      AEC IIs was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay. The apoptotic rate of AEC IIs was analyzed by flow cytometry. The
      oxidative damage was evaluated by flow cytometry and reactive oxygen species
      (ROS) were detected using a 2',7'-dichlorodihydrofluorescein diacetate probe.
      Quantitative polymerase chain reaction and western blotting were used to detect
      the mRNA and protein expression of the SHH signaling molecule Smoothened (SMO).
      The results demonstrated that exposure to 95% oxygen for 24 h significantly
      increased the level of ROS, contributed to apoptosis and markedly decreased the
      proliferation of AEC IIs. Compared with hyperoxia exposure, SP treatment
      decreased the level of ROS, reduced AEC II apoptosis and improved the cell
      survival sequentially. SMO was found to be expressed in AEC IIs and its
      expression increased when the cells were in hyperoxic conditions. These effects
      were enhanced by treatment with SP, which was able to significantly increase the
      expression of SMO. The aforementioned protective effect was weakened following
      treatment with L703.606. These findings suggested that SP was a protective
      regulatory factor that was able to decrease the hyperoxia-induced cell injury and
      death, and improve the survival of AEC IIs exposed to hyperoxia, which may be
      associated with the activation of the SHH signaling pathway.

PMID- 24938871
TI  - Formation mechanism and optimization of highly luminescent N-doped graphene
      quantum dots.
AB  - Photoluminescent graphene quantum dots (GQDs) have received enormous attention
      because of their unique chemical, electronic and optical properties. Here a
      series of GQDs were synthesized under hydrothermal processes in order to
      investigate the formation process and optical properties of N-doped GQDs. Citric
      acid (CA) was used as a carbon precursor and self-assembled into sheet structure
      in a basic condition and formed N-free GQD graphite framework through
      intermolecular dehydrolysis reaction. N-doped GQDs were prepared using a series
      of N-containing bases such as urea. Detailed structural and property studies
      demonstrated the formation mechanism of N-doped GQDs for tunable optical
      emissions. Hydrothermal conditions promote formation of amide between -NH2 and 
      COOH with the presence of amine in the reaction. The intramoleculur dehydrolysis
      between neighbour amide and COOH groups led to formation of pyrrolic N in the
      graphene framework. Further, the pyrrolic N transformed to graphite N under
      hydrothermal conditions. N-doping results in a great improvement of PL quantum
      yield (QY) of GQDs. By optimized reaction conditions, the highest PL QY (94%) of
      N-doped GQDs was obtained using CA as a carbon source and ethylene diamine as a N
      source. The obtained N-doped GQDs exhibit an excitation-independent blue emission
      with single exponential lifetime decay.

PMID- 24938872
TI  - MEK inhibitor effective against proliferation in breast cancer cell.
AB  - The targeted small-molecule drug AZD6244 is an allosteric, ATP-noncompetitive
      inhibitor of MEK1/2 that has shown activity against several malignant tumors.
      Here, we report that AZD6244 repressed cell growth and induced apoptosis and G1
      phase arrest in the breast cancer cell lines MDA-MB-231 and HCC1937. Using
      microRNA (miRNA) arrays and quantitative RT-PCR, we found that miR-203 was up
      regulated after AZD6244 treatment. In accordance with bioinformatics and
      luciferase activity analyses, CUL1 was found to be the direct target of miR-203.
      Furthermore, miR-203 inhibition and CUL1 overexpression reversed the cytotoxicity
      of AZD6244 on the MDA-MB-231 and HCC1937 cells. Collectively, our data indicate
      that miR-203 mediates the AZD6244-induced cytotoxicity of breast cancer cells and
      that the MEK/ERK/miR-203/CUL1 signaling pathway may participate in this process.

PMID- 24938873
TI  - Diverse effect of WWOX overexpression in HT29 and SW480 colon cancer cell lines.
AB  - WW-domain-containing oxidoreductase (WWOX) is the tumour suppressor gene from the
      common fragile site FRA16D, whose altered expression has been observed in tumours
      of various origins. Its suppressive role and influence on basic cellular
      processes such as proliferation and apoptosis have been confirmed in many in
      vitro and in vivo studies. Moreover, its protein is thought to take part in the
      regulation of tissue morphogenesis and cell differentiation. However, its role in
      colon cancer formation remains unclear. The aim of this study was to characterize
      the influence of WWOX on the process of colon cancerogenesis, the basic features
      of the cancer cell and its expression profiles. Multiple biological tests,
      microarray experiments and quantitative reverse transcriptase (RT)-PCR were
      performed on two colon cancer cell lines, HT29 and SW480, which differ in
      morphology, expression of differentiation markers, migratory characteristics and
      metastasis potential and which represent negative (HT29) and low (SW480) WWOX
      expression levels. The cell lines were subjected to retroviral transfection,
      inducting WWOX overexpression. WWOX was found to have diverse effects on
      proliferation, apoptosis and the adhesion potential of modified cell lines. Our
      observations suggest that in the HT29 colon cancer cell line, increased
      expression of WWOX may result in the transition of cancer cells into a more
      normal colon epithelium phenotype, while in SW480, WWOX demonstrated well-known
      tumour suppressor properties. Our results also suggest that WWOX does not behave
      as classical tumour suppressor gene, and its influence on cell functioning is
      more global and complicated.

PMID- 24938874
TI  - The role of microRNAs in human breast cancer progression.
AB  - Over the past decade, microRNAs (miRNAs) have become a new paradigm of gene
      regulation. miRNAs are involved in a wide array of carcinogenic processes.
      Indeed, increasing evidence has shown the importance of miRNAs in cancer,
      suggesting their possible use as diagnostic, predictive and prognostic
      biomarkers, leading to miRNA-based anti-cancer therapies, either alone or in
      combination with current targeted therapies, with the goal of improving cancer
      treatment responses and increasing cure rates. The advantage of using a miRNA
      approach is based on the ability to concurrently target multiple effectors of
      pathways involved in cell proliferation, migration and survival. This review
      sheds new light on miRNA regulation of genes that play critical roles in the
      process of malignant transformation and tumour metastasis, the dysregulation of
      miRNA expression in cancer development and the development of miRNA-based
      diagnostics and therapeutics. 

PMID- 24938875
TI  - Combined effects of CYP1A1 MspI and GSTM1 genetic polymorphisms on risk of lung
      cancer: an updated meta-analysis.
AB  - Genetic polymorphisms of cytochrome P450 1A1 (CYP1A1) and glutathione S
      transferase M1 (GSTM1) genes might contribute to the variability in individual
      susceptibility to lung cancer, but the reported results from individual studies
      are not always consistent. We therefore conducted a meta-analysis to
      systematically estimate the associations between polymorphisms of these two genes
      and risk of lung cancer. Twenty-one studies with 8,926 subjects were finally
      enrolled into this study. Meta-analysis was performed by RevMan 5.2. Odds ratio
      (OR) and its 95 % confidence interval (CI) were calculated to evaluate the
      susceptibility to lung cancer. Compared with the wild-type homozygous genotype,
      significantly elevated risk of lung cancer were associated with variant CYP1A1
      MspI (m1/m2 + m2/m2 vs. m1/m1: OR = 1.27, 95 % CI = 1.12-1.43, P < 0.001) and
      deletion of GSTM1 (null vs. present: OR = 1.26, 95 % CI = 1.13-1.40, P < 0.001).
      Both the two genetic polymorphisms were independently associated with the risk of
      lung cancer. The pooled OR of lung cancer for population with both CYP1A1 MspI
      and GSTM1 mutations (MspI m1/m2 or m2/m2 and GSTM1 null) was 1.62 (95 % CI 1.27
      2.07, P < 0.001) when compared with those without any of the above mutations,
      which is higher than single genetic polymorphism. In the stratified analysis,
      significantly higher risks of lung cancer associated with above genetic
      polymorphisms were found only in Asian population. This meta-analysis suggests
      that the CYP1A1 MspI and GSTM1 polymorphisms correlate with increased lung cancer
      susceptibility independently, and that there is an interaction between the two
      genes. However, the associations vary in different ethnic populations.

PMID- 24938876
TI  - Sexual conflict, life span, and aging.
AB  - The potential for sexual conflict to influence the evolution of life span and
      aging has been recognized for more than a decade, and recent work also suggests
      that variation in life span and aging can influence sexually antagonistic
      coevolution. However, empirical exploration of these ideas is only beginning.
      Here, we provide an overview of the ideas and evidence linking inter- and
      intralocus sexual conflicts with life span and aging. We aim to clarify the
      conceptual basis of this research program, examine the current state of
      knowledge, and suggest key questions for further investigation. 

PMID- 24938877
TI  - Multifunctional supramolecular dendrimers with an s-triazine ring as the central
      core: liquid crystalline, fluorescence and photoconductive properties.
AB  - Novel liquid crystal (LC) dendrimers have been synthesised by hydrogen bonding
      between an s-triazine as the central core and three peripheral dendrons derived
      from bis(hydroxymethyl)propionic acid. Symmetric acid dendrons bearing achiral
      promesogenic units have been synthesised to obtain 3:1 complexes with triazine
      that exhibit LC properties. Asymmetric dendrons that combine the achiral
      promesogenic unit and an active moiety derived from coumarin or pyrene structures
      have been synthesised in order to obtain dendrimers with photophysical and
      electrochemical properties. The formation of the complexes was confirmed by IR
      and NMR spectroscopy data. The liquid crystalline properties were investigated by
      differential scanning calorimetry, polarising optical microscopy and X-ray
      diffractometry. All complexes displayed mesogenic properties, which were smectic
      in the case of symmetric dendrons and their complexes and nematic in the case of
      asymmetric dendrons and their dendrimers. A supramolecular model for the lamellar
      mesophase, based mainly on X-ray diffraction studies, is proposed. The
      electrochemical behaviour of dendritic complexes was investigated by cyclic
      voltammetry. The UV/Vis absorption and emission properties of the compounds and
      the photoconductive properties of the dendrons and dendrimers were also
      investigated. 

PMID- 24938879
TI  - Didemnacerides A and B: two new glycerides from Red Sea ascidian Didemnum
      species.
AB  - Two new glycerides, didemnacerides A (1) and B (2), together with three known
      sterols, 24-ethyl-25-hydroxycholesterol (3), cholest-6-en-3,5,8-triol (4) and
      cholestane-3beta,5alpha,6beta-26-tetrol (5), were isolated from the Red Sea
      ascidian Didemnum sp. Their structures were elucidated by using extensive 1D
      ((1)H, (13)C) and 2D ((1)H-(1)H COSY, HSQC and HMBC) NMR studies and mass
      spectroscopic data (GC-MS and HR-MS) as well as alkaline hydrolysis followed by
      GC-MS and NMR spectral analyses of the fatty acid methyl esters. This is the
      first report of compounds 3-5 from the Red Sea ascidian Didemnum species. 

PMID- 24938878
TI  - Early signs of anomalous neural functional connectivity in healthy offspring of
      parents with bipolar disorder.
AB  - OBJECTIVES: Bipolar disorder (BD) has been associated with dysfunctional brain
      connectivity and with family chaos. It is not known whether aberrant connectivity
      occurs before illness onset, representing vulnerability for developing BD amidst
      family chaos. We used resting-state functional magnetic resonance imaging (fMRI)
      to examine neural network dysfunction in healthy offspring living with parents
      with BD and healthy comparison youth. METHODS: Using two complementary
      methodologies [data-driven independent component analysis (ICA) and hypothesis
      driven region-of-interest (ROI)-based intrinsic connectivity], we examined
      resting-state fMRI data in 8-17-year-old healthy offspring of a parent with BD (n
      = 24; high risk) and age-matched healthy youth without any personal or family
      psychopathology (n = 25; low risk). RESULTS: ICA revealed that, relative to low
      risk youth, high-risk youth showed increased connectivity in the ventrolateral
      prefrontal cortex (VLPFC) subregion of the left executive control network (ECN),
      which includes frontoparietal regions important for emotion regulation. ROI-based
      analyses revealed that high-risk versus low-risk youth had decreased
      connectivities between the left amygdala and pregenual cingulate, between the
      subgenual cingulate and supplementary motor cortex, and between the left VLPFC
      and left caudate. High-risk youth showed stronger connections in the VLPFC with
      age and higher functioning, which may be neuroprotective, and weaker connections
      between the left VLPFC and caudate with more family chaos, suggesting an
      environmental influence on frontostriatal connectivity. CONCLUSIONS: Healthy
      offspring of parents with BD show atypical patterns of prefrontal and subcortical
      intrinsic connectivity that may be early markers of resilience to or
      vulnerability for developing BD. Longitudinal studies are needed to determine
      whether these patterns predict outcomes.

PMID- 24938880
TI  - Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of
      early breast cancer in serum.
AB  - BACKGROUND: MicroRNAs (miRs) represent a distinct class of posttranscriptional
      modulators of gene expression with remarkable stability in sera. Several miRs are
      oncogenic (oncomiRs) and are deregulated in the pathogenesis of breast cancer and
      function to inhibit tumor suppressors. Routine blood monitoring of these
      circulating tumor-derived products could be of significant benefit to the
      diagnosis and relapse detection of early-stage breast cancer (EBC) patients.
      METHODS: Aim of this project was to determine expression of miR-155, miR-19a, miR
      181b, miR-24, relative to let-7a in sera of 63 patients with EBC and 21 healthy
      controls. Longitudinal multivariate data analysis was performed to stochastically
      model the serum levels of each of the oncomiRs during disease phases: from
      diagnosis, after surgery, and following chemo/radiotherapy. Moreover, this
      analysis was utilized to evaluate oncomiR levels in EBC patients subgrouped using
      current clinical prognostic factors including HER2, Ki-67, and grade III.
      RESULTS: EBC patients significantly over-express the oncomiRs at the time of
      diagnosis. Following surgical resection the serum levels of miR-155, miR-181b,
      and miR-24 significantly decreased (p = 1.89e-05, 5.41e-06, and 0.00638,
      respectively) whereas the miR-19a decreased significantly after the therapy (p =
      0.00869). Furthermore, in case of high-risk patients serum levels of miR-155, miR
      19a, miR-181b, and miR-24 are significantly more abundant in comparison to low
      risk group (p = 0.026, 0.02567, 0.0250, and 0.00990) and show a decreasing trend
      upon therapy. CONCLUSIONS: OncomiRs are significantly more abundant in the sera
      of EBC patients compared to controls at diagnosis. Differences in oncomiR levels
      reflecting EBC risk were also observed. Testing the oncomiRs may be useful for
      diagnostic purpose and possibly also for relapse detection in follow-up studies
      of EBC.

PMID- 24938882
TI  - Treatment of celiac disease: from gluten-free diet to novel therapies.
AB  - Gluten-free diet (GFD) is the cornerstone treatment for celiac disease (CD). This
      diet excludes the protein gluten a protein forum in in grains such as wheat,
      barley, rye and triticale. Gluten causes small intestines inflammation in
      patients with CD and eating a GFD helps these patients in controlling signs and
      symptoms and prevent complications. Following a GFD may be frustrating, however,
      it is important to know that plenty of foods are naturally gluten-free and
      nowadays is relatively easy to find substitutes for gluten-containing foods.
      Certain grains, such as oats, are generally safe but can be contaminated with
      wheat during growing and processing stages of production. For this reason, it is
      generally recommended avoiding oats unless they are specifically labelled gluten
      free. Other products that may contain gluten include food additives, such as malt
      flavouring, modified food starch and some supplement and/or vitamins that use
      gluten as a binding agent. Cross-contamination occurs when gluten-free foods come
      into contact with foods that contain gluten. It can happen during the
      manufacturing process or if the same equipment is used to make a variety of
      products. Cross-contamination can also occur at home if foods are prepared on
      common surfaces or with utensils that have not been cleaned after being used to
      prepare gluten-containing foods (using a toaster for gluten-free and regular
      bread). Although safe and effective, the GFD is not ideal: it is expensive, of
      limited nutritional value, and not readily available in many countries.
      Consequently, a need exists for novel, non-dietary therapies for celiac disease.
      Advances in understanding the immunopathogenesis of CD have suggested several
      types of therapeutic strategies alternative to the GFD. Some of these strategies
      attempt to decrease the immunogenicity of gluten-containing grains by
      manipulating the grain itself or by using oral enzymes to break down immunogenic
      peptides that normally remain intact during digestion. Other strategies focus on
      preventing the absorption of these peptides, preventing tissue transglutaminase
      from rendering gluten peptides more immunogenic, or inhibiting their binding to
      CD-specific antigen-presenting molecules. Strategies that limit T cell migration
      to the small intestine or that re-establish mucosal homeostasis and tolerance to
      gluten antigens are also being explored.

PMID- 24938881
TI  - Protective effects of certain pharmaceutical compounds against abrin induced cell
      death in Jurkat cell line.
AB  - Abrin is a plant glycoprotein toxin from the seeds of Abrus precatorius, and
      shares the structure and properties with ricin. Abrin is highly toxic, with an
      estimated human fatal dose of 0.1-1 MUg/kg, causing death after accidental and
      intentional poisoning. It is a potent toxin warfare agent. There are no antidotes
      available for abrin intoxication. It is becoming increasingly important to
      develop countermeasures for abrin by developing pre- and post-exposure medical
      therapy. The present study involves the screening of certain pharmaceutical
      agents for their potential to counter abrin toxicity in Jurkat T lymphocytes and
      the probable mechanism of action of the compounds with protective effect. The
      compounds studied are: Prednisolone, Minocycline, Amifostine, DRDE-07 (amifostine
      analog), Melatonin, Ebselen, N-Acetyl-l-cysteine (NAC) and Trolox. Among them,
      only NAC and trolox were found to confer significant protection in Jurkat cells
      by restoring antioxidant enzymes depleted by abrin treatment. Abrin also shown to
      increase in stress factor associated proteins SAPK/JNK, c-fos and c-jun levels
      which were effectively suppressed by NAC and trolox. In addition to this, both
      compounds significantly inhibit abrin induced inflammation and caspase-3
      activity. These data suggest that NAC and trolox may serve as potential
      candidates for management of abrin-induced poisoning.

PMID- 24938883
TI  - Prevalence of IgE mediated cow's milk and egg allergy in children under 2 years
      of age in Sanliurfa, Turkey: the city that isn't almost allergic to cow's milk.
AB  - AIM: Food allergy is a common problem in children and adults. The aim of this
      study was to determine the frequency of cow's milk and egg allergy based on skin
      prick test and oral food challenge results METHODS: We recruited 614 children
      aged 1 month-2 years in from different areas of Sanliurfa. An interview was
      conducted with each parents and family demographic, and prenatal-antenatal
      postnatal information was recorded, then skin prick test was applied to the
      children for egg white, egg yolk and cow's milk. Cases that are required, sIgE
      levels for cow's milk, egg white and egg yolk were measured and food challenge
      tests were applied. RESULTS: Cow's milk and egg allergy was determined in 1 case
      (0.16%) and 8 cases (1.30%) respectively from the results of the tests applied.
      Six cases (0.97%) were accepted as sensitive to egg white and egg yolk. Within
      the factors which were questioned, (only the egg allergy evaluation was made
      without the cow's milk allergy case) of those with parental consanguinity was
      determined at a statistically significantly high level (OR=5.8, 95% CI: 1.2-27.2,
      P=0.01). CONCLUSION: The prevalence of cow's milk allergy in Sanliurfa is the
      lowest reported prevalence rate to date in children under 2 years of age. When
      infants develop a food allergy, this takes the form of egg allergy. Within the
      several factors evaluated to explain this situation, a significant relationship
      was determined only with parental consanguinity. However, as reported above, to
      date there is no genetic or epidemiological study to explain this situation.

PMID- 24938884
TI  - Structure and electronic properties of in situ synthesized single-layer MoS2 on a
      gold surface.
AB  - When transition metal sulfides such as MoS2 are present in the single-layer form,
      the electronic properties change in fundamental ways, enabling them to be used,
      e.g., in two-dimensional semiconductor electronics, optoelectronics, and light
      harvesting. The change is related to a subtle modification of the band structure
      due to confinement in the direction perpendicular to the sheets, and there is a
      considerable interest in understanding how this modification can be controlled
      and adjusted to generate 2D-materials with functional properties. In this article
      we report a synthesis procedure together with scanning tunneling microscopy and X
      ray photoelectron spectroscopy characterization of two-dimensional single-layer
      islands of MoS2 synthesized directly on a gold single crystal substrate. Thanks
      to a periodic modulation of the atom stacking induced by the lattice mismatch, we
      observe a structural buckling of the MoS2 layer resulting in a characteristic
      moire pattern. X-ray photoelectron spectroscopy indicates that the system
      develops the characteristics of n-doped MoS2 due to electron donation. Scanning
      tunneling spectroscopy furthermore reflects a convolution of MoS2 and Au donor
      states where the MoS2 band structure appears modified at the band gap edges. This
      electronic effect is further modulated by the moire periodicity and leads to
      small substrate-induced electronic perturbations near the conduction band minimum
      in the band gap of MoS2. The results may be highly relevant in the context of
      nanopatterned two-dimensional materials on metal surfaces, and we propose the
      MoS2/Au system in this article as a promising candidate to further explore the
      properties of supported 2D transition-metal dichalcogenides. 

PMID- 24938885
TI  - Self-assembly of colloid-cholesteric composites provides a possible route to
      switchable optical materials.
AB  - Colloidal particles dispersed in liquid crystals can form new materials with
      tunable elastic and electro-optic properties. In a periodic 'blue phase' host,
      particles should template into colloidal crystals with potential uses in
      photonics, metamaterials and transformational optics. Here we show by computer
      simulation that colloid/cholesteric mixtures can give rise to regular crystals,
      glasses, percolating gels, isolated clusters, twisted rings and undulating
      colloidal ropes. This structure can be tuned via particle concentration, and by
      varying the surface interactions of the cholesteric host with both the particles
      and confining walls. Many of these new materials are metastable: two or more
      structures can arise under identical thermodynamic conditions. The observed
      structure depends not only on the formulation protocol but also on the history of
      an applied electric field. This new class of soft materials should thus be
      relevant to design of switchable, multistable devices for optical technologies
      such as smart glass and e-paper. 

PMID- 24938886
TI  - Standardization of blood smears prepared in transparent acetate: an alternative
      method for the microscopic diagnosis of malaria.
AB  - BACKGROUND: Due to students' initial inexperience, slides are frequently broken
      and blood smears are damaged in microscopy training, leading to the need for
      their constant replacement. To minimize this problem a method of preparing blood
      smears on transparent acetate sheets was developed with the goal of implementing
      appropriate and more readily available teaching resources for the microscopic
      diagnosis of malaria. METHODS: Acetate sheets derived from polyester were used to
      standardize the preparation and staining of thin and thick blood smears on
      transparent acetate sheets. Thick and thin blood smears were also prepared using
      the conventional method on glass slides. The staining was conducted using Giemsa
      staining for the thick and thin smears. RESULTS: Microscopic examination (1,000x)
      of the thin and thick blood smears prepared on transparent acetate produced high
      quality images for both the parasites and the blood cells. The smears showed up
      on a clear background and with minimal dye precipitation. It was possible to
      clearly identify the main morphological characteristics of Plasmodium,
      neutrophils and platelets. After 12 months of storage, there was no change in
      image quality or evidence of fungal colonization. CONCLUSION: Preparation of thin
      and thick blood smears in transparent acetate for the microscopic diagnosis of
      malaria does not compromise the morphological and staining characteristics of the
      parasites or blood cells. It is reasonable to predict the applicability of
      transparent acetate in relevant situations such as the training of qualified
      professionals for the microscopic diagnosis of malaria and the preparation of
      positive specimens for competency assessment (quality control) of professionals
      and services involved in the diagnosis of malaria.

PMID- 24938887
TI  - The antidiabetic therapeutic potential of dietary polyphenols.
AB  - Type-2 diabetes (T2D) is a complex metabolic syndrome that is characterized by
      persistent hyperglycemia due to either lack of insulin secretion and/or insulin
      resistance. The prevalence of T2D along with its major risk factor, obesity, has
      been increasing with an epidemic proportion in recent years. To date, there is no
      drug of cure for diabetes and the existing therapeutic approaches have serious
      drawbacks including side effects and loss of efficacy during prolonged use.
      Dietary polyphenols are one group of natural products that have shown promise as
      potential antidiabetic agents. In this review, their molecular mechanisms of
      action including, antioxidant, anti-inflammatory, receptor agonist/antagonist
      effect and modulation of key signal transduction cascades, glucose transport,
      enzyme activity, receptor agonistic/antagonist effect, etc. in major insulin
      sensitive cells are discussed. 

PMID- 24938888
TI  - Current and future therapies targeting the immune system in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      (CNS). The exact pathomechanism is unknown, but an aberrant immune response
      against CNS antigens, leading to inflammation in brain and spinal cord followed
      by demyelination, axonal damage and scar formation, seems to play a major role.
      Later in the disease course, inflammation decreases, while neurodegeneration
      proceeds. Approximately 80% of the patients initially show a relapsing-remitting
      disease course (RRMS), but the majority of them later develops a secondary
      progressive MS (SPMS). A minority suffers from primary progressive MS (PPMS).
      Primary goals of long-term MS therapy are to prevent relapses and disease
      progression. Assuming that MS is an autoimmune disease, most therapeutics aim to
      modulate or suppress the immune system. Until now many drugs have proven efficacy
      in RRMS, but none in PPMS. Interferon-beta (IFN-beta) and glatiramer acetate are
      known in RRMS therapy for years. Based on preclinical research and clinical
      trials, new treatment strategies have emerged and have been transferred from
      bench to bedside. The alpha4beta-integrin-antagonist natalizumab was approved in
      2005. Fingolimod, dimethyl fumarate and teriflunomide were the first oral drugs
      introduced in MS therapy. Recently alemtuzuab, another monoclonal antibody, was
      approved in Europe. Promising future perspectives are alemtuzumab, daclizumab,
      and laquinimod. Here, we review drug mechanisms in the therapy of MS. The
      mechanisms of action and the effect of the drugs on the immune system are
      summarized. We report recent results of clinical trials, highlight special
      features of different treatment strategies, and discuss future perspectives and
      ongoing clinical trials. 

PMID- 24938889
TI  - Polyphenols: well beyond the antioxidant capacity: gallic acid and related
      compounds as neuroprotective agents: you are what you eat!
AB  - Gallic acid (3,4,5-trihydroxybenzoic acid) is a phenolic acid widely distributed
      in many different families of higher plants, both in free state, and as a part of
      more complex molecules, such as ester derivatives or polymers. In nature, gallic
      acid and its derivatives are present in nearly every part of the plant, such as
      bark, wood, leaf, fruit, root and seed. They are present in different
      concentrations in common foodstuffs such as blueberry, blackberry, strawberry,
      plums, grapes, mango, cashew nut, hazelnut, walnut, tea, wine and so on. After
      consumption, about 70% of gallic acid is adsorbed and then excreted in the urine
      as 4-O-methylgallic acid. Differently, the ester derivatives of gallic acid, such
      as catechin gallate ester or gallotannins, are hydrolyzed to gallic acid before
      being metabolized to methylated derivatives. Gallic acid is a well known
      antioxidant compounds which has neuroprotective actions in different models of
      neurodegeneration, neurotoxicity and oxidative stress. In this review, we discuss
      about the neuroprotective actions of gallic acid and derivatives and their
      potential mechanisms of action. 

PMID- 24938890
TI  - Resveratrol as a protective molecule for neuroinflammation: a review of
      mechanisms.
AB  - Under normal conditions, most of the central nervous system (CNS) is protected by
      the blood brain barrier (BBB) from systemic inflammation progression and from the
      infiltration of immune cells. As a consequence, the CNS developed an original way
      to provide surveillance, defense and repair, which relies on the complex process
      of neuroinflammation. Despite tight regulation, neuroinflammation is frequently
      the cause of irreversible nerve cell loss but it is also where the solution lies.
      Specific immune crosstalk taking place in the CNS needs to be decoded in order to
      identify the best therapeutic strategies aimed at helping the CNS restore
      homeostasis in difficult conditions such as in neurodegenerative disorders. This
      review deals with the double-edged sword nature of neuroinflammation and the use
      of resveratrol in various models as one of the most promising therapeutic
      molecules for preventing the consequences of nerve cell autodestruction. 

PMID- 24938891
TI  - Tea consumption and risk of ischemic stroke: a brief review of the literature.
AB  - Stroke is an important cerebrovascular disease which causes chronic disability
      and death in patients. Despite of its high morbidity and mortality, there are
      limited available effective neuroprotective agents for stroke. In recent years,
      the research aimed at finding novel neuroprotective agents from natural origins
      has been intensified. Camellia sinensis L. (tea) is the second most consumed
      beverage worldwide, after water. It is classified into green and white, oolong,
      black and red, and Pu-erh tea based on the manufacturing process. Catechins are
      the main phytochemical constituents of Camellia sinensis which are known for
      their high antioxidant capacity. On other hand, it is well known that oxidative
      stress plays an important role in the initiation and progression of different
      cardiovascular diseases such as stroke. Therefore, the present article is aimed
      to review scientific studies that show the protective effects of tea consumption
      against ischemic stroke. 

PMID- 24938892
TI  - Cellular delivery of noncovalently-associated macromolecules by cell-penetrating
      peptides.
AB  - Cellular and nuclear delivery of biomolecules is limited by low membrane
      permeability. Cell-penetrating peptides (CPPs) can be covalently linked to cargos
      to improve cellular internalization. Our work indicates that arginine-rich CPPs
      are also able to interact with a variety of cargos, including DNA, RNA, proteins
      and nanomaterials, in a noncovalent manner and subsequently effect their delivery
      into cells. The advantages of noncovalent attachment in CPP-mediated transduction
      are multiple: ease of use, ease of production, and versatility with respect to
      both cargo composition and functional delivery (i.e., the cargo is not chemically
      modified). We have extended this approach to achieve simultaneous transduction of
      covalently and noncovalently associated complexes, opening a new method for
      delivering multiple types of cargos, including proteins, fluorescent
      nanomaterials, nucleic acid and others. These novel variations of CPP-mediated
      transport should be of broad utility in the transport of genes, small interfering
      RNAs, proteins and nanoparticles in biomedical research and therapeutic
      intervention. 

PMID- 24938893
TI  - Harnessing the capacity of cell-penetrating peptides for drug delivery to the
      central nervous system.
AB  - The existence of blood-brain barrier (BBB) represents the most formidable
      challenge for drug delivery to the central nervous system (CNS). Modern
      breakthrough in biology offers multiple choices for overcoming this barrier but
      yields modest outcomes for clinical application due to various problems such as
      safety concerns, insufficient delivery efficiency and poor penetration. Cell
      penetrating peptides (CPPs) possessing powerful transmembrane capacity have been
      shown to be effective transport vectors for bioactive molecules and an attractive
      alternative to traditional active targeting approaches. However, the non
      specificity of CPPs has hindered them from targeting a desired site of action.
      Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with
      specific targeting property may extricate CPPs from the dilemma. In this review,
      both the traditional and novel applications of CPPs-based strategies for CNS drug
      delivery will be discussed. 

PMID- 24938894
TI  - Cell-penetrating peptide-mediated topical delivery of biomacromolecular drugs.
AB  - Biomacromolecules play an important role in the treatment of many diseases, but
      their topical application has been limited by their poor cell membrane
      permeability. Cell-penetrating peptides (CPPs) have been investigated over the
      past few decades as a potential strategy to overcome this challenge. CPPs can
      effectively mediate the cellular uptake of poorly internalized biomacromolecules
      without unfavorable side effects and have therefore attracted considerable
      interest as a viable alternative to existing parenteral therapies involving
      biomacromolecules. In this review, we will highlight the application of CPPs to
      the non-invasive delivery of biomacromolecules, with a focus on percutaneous and
      nasal absorption of biomacromolecules administered using CPPs. 

PMID- 24938895
TI  - Cell penetrating peptides and the mechanisms for intracellular entry.
AB  - A major thrust in the biomedical and pharmaceutical industries is to develop
      diagnostic and therapeutic tools that have significantly improved selectivity and
      specificity compared to the current state-of-the-art. This has driven much of the
      effort to look at molecules and materials that are significantly larger than the
      traditional small molecule agents. Due to size restrictions, however, many of
      these materials are unable to penetrate the cell membrane and gain access to the
      intracellular components on which they exert their action. The relatively recent
      discovery of cell penetrating peptides (CPP) provides a powerful tool that has
      enabled the intracellular delivery of these materials. While a variety of
      proteins, DNA, polymers and even nanoparticles have been successfully delivered
      into cells, there still remains some debate as to the mechanism of entry utilized
      by the CPPs. In this review, we provide a brief outline of the different
      potential mechanisms for cellular uptake of CPPs. 

PMID- 24938896
TI  - Cell-penetrating peptide-based intelligent liposomal systems for enhanced drug
      delivery.
AB  - Liposomes are widely used as drug delivery systems and several liposome-based
      nanomedicines have been approved for clinical use. Cell penetrating peptides
      (CPPs) have been decorated onto nanoparticulated vesicle such as liposomes to
      further improve the intracellular delivery efficiency. However, the poor
      selectivity of CPPs hindered their application, especially in the in vivo
      application. To resolve this issue, several strategies have been developed,
      including shielding and environment-triggered deshielding of CPPs as well as
      designing of environment-responsive CPPs and specific- targeting CPPs and last
      but not least, combination strategy. In this review, the abovementioned
      strategies were discussed. 

PMID- 24938897
TI  - Papanicolaou tests with coexisting squamous and glandular abnormalities.
AB  - BACKGROUND: Papanicolaou (Pap) test interpretations of atypical glandular cells
      are associated with subsequent detection of squamous and, less often, glandular
      malignancies. A Pap test with a combined interpretation of squamous and glandular
      atypia indicates concern for either 2 distinct lesions (both squamous and
      glandular) or involvement of cervical squamous and glandular epithelium by a
      single pathologic process. Dual interpretations can potentially guide patient
      management. This retrospective study describes an institutional experience with
      Pap test dual reporting of squamous and glandular atypia and patient follow-up in
      these cases. METHODS: Following institutional review board approval, a search of
      the anatomic pathology database for Pap tests with both atypical squamous and
      atypical glandular interpretations from January 2005 to December 2010 was
      performed. Other recorded data included: prior history, age, human papillomavirus
      (HPV) status, and most severe follow-up histologic diagnosis. RESULTS: Of 361,953
      Pap tests interpreted in the laboratory during this period, a total of 230
      (0.06%) patients with dual interpretation Pap tests and follow-up were
      identified. Follow-up pathology results on these patients were predominantly
      squamous lesions (51.7%). Glandular lesions only were detected in 14 cases
      (6.1%). Nine (3.9%) patients had both squamous and glandular pathology.
      CONCLUSIONS: Over a 6-year period, dual Pap test interpretations with both
      squamous and glandular atypia were more often associated with squamous than
      glandular lesions. Dual interpretations did identify coexisting squamous and
      glandular lesions. However, the number of cases was small.

PMID- 24938898
TI  - Pro-apoptotic effects of the novel tangeretin derivate 5-acetyl-6,7,8,4'
      tetramethylnortangeretin on MCF-7 breast cancer cells.
AB  - Citrus polymethoxyflavone tangeretin (5,6,7,8,4'-pentamethoxyflavone, TAN)
      displays multiple biological activities, but previous reports showed that TAN
      failed to induce MCF-7 human breast cancer cells apoptosis. Herein, we prepared 5
      acetyl-6,7,8,4'-tetramethylnortangeretin (5-ATAN), and evaluated its cytotoxicity
      on MCF-7 cells. 5-ATAN revealed stronger cytotoxicity than that of parent TAN in
      the growth inhibition of MCF-7 cells. 5-ATAN induced apoptosis via both caspase
      independent and -dependent pathways, in which 5-ATAN induced the translocation of
      apoptosis inducing factor and phosphorylation of H2AX as well as poly (ADP
      ribose) polymerase cleavage, caspase-3 activation. However, 5-ATAN did not affect
      extrinsic markers caspase-8, BID, and FADD. Further, 5-ATAN induced the loss of
      mitochondrial membrane potential (Deltapsim) by regulating the Bax/Bcl-2 ratio.
      Loss of Deltapsim led to the mitochondrial release of cytochrome c which
      triggered activation of caspase-9. In conclusion, these data indicate that 5-ATAN
      plays pro-apoptotic cytotoxic roles in MCF-7 cells through both caspase-dependent
      intrinsic apoptosis and caspase-independent apoptosis pathways.

PMID- 24938899
TI  - Analysis of influence of baicalin joint resveratrol retention enema on the TNF
      alpha, SIgA, IL-2, IFN-gamma of rats with respiratory syncytial virus infection.
AB  - Explore the influence of baicalin joint resveratrol retention enema on TNF-alpha,
      SIgA, IL-2, and IFN-gamma of rats with respiratory syncytial virus (RSV)
      infection. The 60 SD rats were randomly divided into normal group, model group,
      baicalin group, resveratrol group, joint group, and ribavirin group. For model
      group, baicalin group, resveratrol group, joint group, and ribavirin group, rats
      were given RSV virus suspension intranasally for 3 days, and model group was not
      given administration. Baicalin group, resveratrol group, joint group, and
      ribavirin group were, respectively, given baicalin 100 mg/kg/day, resveratrol 30
      mg/kg/day, baicalin joint resveratrol, and ribavirin 1 g/kg/day retention enema.
      After continuously given administration 7 days, rats were measured in serum TNF
      alpha, IL-2, IFN-gamma levels and SIgA levels in bronchoalveolar lavage fluid.
      Model group, TNF-alpha, IL-2, IFN-gamma, and SIgA were significantly higher than
      the normal group (P < 0.05); Baicalin group, resveratrol group, ribavirin group,
      TNF-alpha, IL-2, IFN-gamma, and SIgA were significantly higher than the model
      group (P < 0.05); TNF-alpha, IL-2 between baicalin group, resveratrol group,
      ribavirin group, have no significant difference (P > 0.05); Baicalin group,
      resveratrol group, joint group, IFN-gamma, and SIgA were significantly higher
      than the ribavirin group (P < 0.05); Joint group TNF-alpha, IL-2, IFN-gamma, and
      SIgA were significantly higher than baicalin group, resveratrol group, and
      ribavirin group (P < 0.05). Baicalin joint resveratrol retention enema can
      increase RSV infection model in rats serum TNF-alpha, IL-2, IFN-gamma levels and
      SIgA levels in bronchoalveolar lavage fluid, which may anti-virus through this
      mechanism.

PMID- 24938900
TI  - Type 1 diabetes mellitus is an independent risk factor for pulmonary fibrosis.
AB  - The objective of this study was to assess the clinical and histopathological
      relationship between pulmonary fibrosis and type 1 diabetes. We examined clinical
      pulmonary function parameters and transbronchial lung biopsies to assess
      associated histopathological changes in 12 type 1 diabetic patients presenting
      with dyspnea. Lung CT images pulmonary function tests from 12 diabetic patients
      without dyspnea and from 12 matched normal subjects served as controls. A similar
      histopathological analysis, including cytokine levels and pro-fibrotic markers,
      was performed on lung tissues in mice after the induction of experimental
      diabetes in an attempt to strengthen the link between diabetes and pulmonary
      fibrosis. Pulmonary function parameters (FVC, FEV1, TLC, and DLco/VA) were
      significantly reduced in diabetic patients with dyspnea and without dyspnea,
      compared to controls. Both patient groups also had increased lung CT scores and
      symptoms compared to normal controls, though the greatest increases were in the
      diabetic patients with dyspnea. Chronic hyperglycemia induced in mice led to
      histopathological changes in the lungs that were similar to those found in the
      human diabetic subjects and included alveoli compression by hyperplastic
      interstitium infiltrated with inflammatory cells and fibrotic in nature. Two
      inflammatory related genes, TNF-alpha and PAI-1, and two fibrosis-related genes,
      CTGF and fibronectin, demonstrated increased mRNA and protein expression in
      diabetic mouse lungs. In conclusion, there were significant clinical and
      histopathological correlations between pulmonary fibrosis and the presence of
      type 1 diabetes. Diabetes was clinically associated with pulmonary fibrosis and
      dysfunction in humans, and diabetes induction led to a similar pulmonary fibrosis
      in an experimental model. These clinical and non-clinical data suggest that
      diabetes is an independent risk factor for pulmonary fibrosis. 

PMID- 24938901
TI  - Correlation between the rupture risk and 3D geometric parameters of saccular
      intracranial aneurysms.
AB  - The purpose of this study is to evaluate the association of the location and
      geometric parameters of intracranial aneurysm with the risk of rupture. A
      retrospective study consisted of 284 patients diagnosed with saccular
      intracranial aneurysm between January 2009 and May 2013 at Wuxi Third People's
      Hospital was conducted. 3D digital subtraction angiography images from all
      patients (240 ruptured, 44 unruptured) were obtained and analyzed. The location
      of the aneurysms and the 3D geometric parameters including the aneurysm depth,
      the neck size, diameter of the parent artery, aneurysm angle, aspect radio, size
      ratio, and the neck-to-parent-artery ratio (NPR) were compared between ruptured
      and unruptured groups. RESULTS: In ruptured group, anterior communicating artery,
      posterior communicating artery (PCoA), and the bifurcation of internal carotid
      artery (ICA) were the top three locations for aneurysm occurrence, accounting for
      40.00, 30.42, and 12.08 % respectively. While in the unruptured group, top three
      locations were PCoA (36.36 %), posterior cerebral circulation (18.18 %), and the
      bifurcation of the ICA (15.91 %). Distribution of aneurysm location is
      significantly different (p < 0.05) between ruptured and unruptured aneurysms. For
      the 3D geometric parameters characterizing aneurysm, aneurysm depth (p < 0.05),
      parent artery diameter (p < 0.05), aneurysm angle (p < 0.01), aspect ratio (p <
      0.01), and size ratio (p < 0.01) all showed a significant difference between
      ruptured and unruptured group. No difference was found in the neck size and the
      NPR ratio between the two groups. 3D geometric parameters such as aneurysm depth,
      parent artery diameter, aneurysm angle, aspect ratio, and size ratio can be
      helpful in evaluating the rupture risk of saccular intracranial aneurysm for a
      better prevention and prognosis.

PMID- 24938902
TI  - Cyclin-dependent kinase inhibitors, p16 and p27, demonstrate different expression
      patterns in thymoma and thymic carcinoma.
AB  - OBJECTIVES: The role of cell cycle inhibitors in tumorigenesis has been proven in
      various neoplasms; however, their roles in thymic tumors are still unclear. We
      examined the expression of cell cycle inhibitors such as those of the Cip/Kip
      family (p21, p27, and p57) and the INK-4/ARF family (p16 and p14) in thymoma and
      thymic carcinoma. METHODS: Samples from 41 thymoma and 14 thymic carcinoma
      patients, and 34 normal thymic tissue samples were prepared for the study.
      Immunohistochemical analysis using antibodies to p21, p27, p57, p16, and p14 was
      carried out, and the positivity for these inhibitors in each group was estimated
      in terms of their subcellular location and percentage of cells showing positive
      staining. RESULTS: Nuclear p27 showed a stepwise decrease (p < 0.0001), and the
      cytoplasmic p27 showed a stepwise increase (p < 0.0001) in expression level with
      the increase in malignancy. p16 in both the nucleus and cytoplasm showed a
      stepwise increase (p < 0.0001) in expression level with the increase in
      malignancy. However, as for p21, p57, and p14, there was almost no nuclear or
      cytoplasmic expression in each group. CONCLUSIONS: Our findings suggest that low
      nuclear and high cytoplasmic p27 expression levels, and high nuclear and
      cytoplasmic p16 expression levels may correlate with the increase in thymic
      malignancy.

PMID- 24938903
TI  - Accessible or inaccessible? Diagnostic efficacy of CT-guided core biopsies of
      head and neck masses.
AB  - PURPOSE: Tissue sampling of lesions in the head and neck is challenging due to
      complex regional anatomy and sometimes necessitates open surgical biopsy.
      However, many patients are poor surgical candidates due to comorbidity. Thus, we
      evaluated the use of CT guidance for establishing histopathological diagnosis of
      head and neck masses. METHODS: All consecutive patients (n = 22) who underwent CT
      guided core biopsy of head or neck masses between April 2009 and August 2012 were
      retrospectively reviewed using the departmental CT interventional procedures
      database. The indication for each biopsy performed was to establish or exclude a
      diagnosis of neoplasia in patients with suspicious head or neck lesions found on
      clinical examination or imaging studies. Patients received conscious sedation and
      18 G, semiautomated core needle biopsies were performed by experienced
      neuroradiologists using 16-slice multidetector row CT imaging guidance (Somatom
      Definition Siemens Medical Solutions, Germany). Histopathology results of each
      biopsy were analysed. RESULTS: Sixteen of 22 biopsies that were performed (73 %)
      yielded a pathological diagnosis. Anatomic locations biopsied included:
      masticator (n = 7), parapharyngeal (n = 3), parotid (n = 3), carotid (n = 3),
      perivertebral (n = 3), pharyngeal (n = 2), and retropharyngeal (n = 1) spaces.
      Six biopsies (27 %) were nondiagnostic due to inadequate tissue sampling,
      particularly small biopsy sample size and failure to biopsy the true sampling
      site due to extensive necrosis. No major complications were encountered.
      CONCLUSIONS: The use of CT guidance to perform core biopsies of head and neck
      masses is an effective means of establishing histopathological diagnosis and
      reduces the need for diagnostic open surgical biopsy and general anaesthesia.

PMID- 24938905
TI  - Percutaneous radiofrequency ablation of lung cancer presenting as ground-glass
      opacity.
AB  - PURPOSE: We retrospectively evaluated the outcomes of lung cancer patients
      presenting with ground-glass opacity (GGO) who received radiofrequency ablation
      (RFA). METHODS: Sixteen patients (5 men and 11 women; mean age, 72.6 years) with
      17 lung cancer lesions showing GGO (mean long axis diameter, 1.6 cm) underwent a
      total of 20 percutaneous computed tomography (CT) fluoroscopy-guided RFA
      sessions, including three repeated sessions for local progression. Lung cancer
      with GGO was defined as a histologically confirmed malignant pulmonary lesion
      with a GGO component accounting for >50 % of the lesion on high-resolution CT.
      Procedure outcomes were evaluated. RESULTS: There were no major complications.
      Pneumothorax occurred in 15 of 20 treatment sessions: 14 were asymptomatic, and 1
      required chest tube placement but resolved satisfactorily within 48 h. Minor
      pulmonary hemorrhage occurred in two and mild pneumonitis in one. The median
      tumor follow-up period was 61.5 (range 6.1-96.6) months. The effectiveness rates
      of the primary and secondary techniques were 100 and 100 % at 1 year, 93.3 and
      100 % at 2 years, and 78.3 and 92.3 % at 3 years, respectively. The median
      patient follow-up period was 65.6 (range 6.1-96.6) months. One patient died owing
      to recurrent other cancer 11.7 months after RFA, whereas the other 15 remained
      alive. Overall survival and disease-specific survival rates were 93.3 and 100 %
      at 1 year and 93.3 and 100 % at 5 years, respectively. CONCLUSIONS: RFA for lung
      cancer with GGO was safe and effective, and resulted in promising survival rates.

PMID- 24938904
TI  - Microwave ablation (MWA) for the treatment of a solitary, chemorefractory
      testicular cancer liver metastasis.
AB  - We present a case of a patient with stage IIIC metastatic seminoma with a
      persistent chemorefractory liver lesion. The patient was deemed a poor surgical
      candidate due to the tumor's aggressive biology with numerous other liver lesions
      treated with chemotherapy and a relatively high probability for additional
      recurrences. Further chemotherapy with curative intent was not a feasible option
      due to the fact that the patient had already received second-line high-dose
      chemotherapy and four cycles of third-line treatment complicated by renal
      failure, refractory thrombocytopenia, and debilitating neuropathy. After initial
      failure of laser, microwave ablation of the chemorefractory liver metastasis
      resulted in prolonged local tumor control and rendered the patient disease-free
      for more than 35 months, allowing him to regain an improved quality of life.

PMID- 24938906
TI  - Geometrical factors influencing the hemodynamic behavior of the AAA stent grafts:
      essentials for the clinician.
AB  - Endovascular aneurysm repair (EVAR) is considered to be the treatment of choice
      for abdominal aortic aneurysms (AAA). Despite the initial technical success, EVAR
      is amenable to early and late complications, among which the migration of the
      endograft (EG) with subsequent proximal endoleak (Type Ia) leads to
      repressurization of the AAA sac, exposure to excessive wall stress, and, hence,
      to potential rupture. This article discusses the influence that certain
      geometrical factors, such as neck angulation, iliac bifurcation, EG curvature,
      neck-to-iliac diameter, and length ratios, as well as iliac limbs configuration
      can exert on the hemodynamic behavior of the EGs. The information provided could
      help both clinicians and EG manufacturers towards further development and
      improvement of EG designs and better operational planning. 

PMID- 24938908
TI  - A commentary on: Risk factors for nonorganic low back pain in patients with
      workers' compensation.

PMID- 24938907
TI  - Safety and efficacy of bleomycin sclerotherapy for microcystic lymphatic
      malformation.
AB  - PURPOSE: Sclerotherapy is the mainstay of treatment of macrocystic lymphatic
      malformation (LM), but the response using traditional sclerosants is much less
      beneficial in microcystic lesions. Intralesional bleomycin has been reported to
      be effective in microcystic LM; however, its use is limited by concerns about
      pulmonary fibrosis. The purpose of this study was to evaluate the safety and
      efficacy of bleomycin sclerotherapy in microcystic LM. METHODS: The medical
      records and imaging studies of all patients with microcystic or combined LM who
      underwent percutaneous image-guided sclerotherapy using bleomycin were
      retrospectively reviewed. Only patients with pre- and postprocedure imaging were
      included. Thirty-one patients with a mean age of 13.4 years (range 3 months-31
      years) were treated. Response was graded as complete (>90% size reduction),
      partial (25-90%), or minimal/no response (<25%). Pulmonary function tests (PFT)
      and chest X-rays were performed before the procedure. PFT were repeated at 6
      months and 1 year postprocedure. Annual postprocedure chest X-rays were also
      performed. RESULTS: The malformations were located in the head and neck (n = 27)
      and trunk (n = 4). The number of procedures ranged from 1 to 4 (mean 1.7). Up to
      1 U/kg of bleomycin was injected per session, with a maximum of 15 U. The mean
      follow-up period was 3.2 years (range 1.5-5 years). There was complete response
      in 38% (n = 12), partial response in 58% (n = 18), and no response in 3% (n = 1).
      No complications were identified. CONCLUSIONS: Preliminary indicate that
      sclerotherapy of microcystic LMs using bleomycin is effective and safe.

PMID- 24938909
TI  - Commentary on: "Sagittal alignment as a predictor of clinical adjacent segment
      pathology requiring surgery after anterior cervical arthrodesis".

PMID- 24938910
TI  - Re: Infection after vertebroplasty or kyphoplasty. A series of nine cases and
      review of literature. Spine J 13:1809-17.

PMID- 24938911
TI  - Levels of evidence of clinical spinal research published in the highest impact
      medical journals.

PMID- 24938912
TI  - Decision making about medical interventions in the end-of-life care of people
      with intellectual disabilities: a national survey of the considerations and
      beliefs of GPs, ID physicians and care staff.
AB  - OBJECTIVE: This paper explores the personal beliefs and specific considerations
      of professionals regarding decisions about potentially burdensome medical
      interventions in the end-of-life care for people with intellectual disabilities
      (ID). METHODS: A survey questionnaire covering decision making about potentially
      burdensome medical interventions was sent to nationally representative samples of
      294 ID care staff-members, 273 ID physicians and 1000 GPs. RESULTS: Professionals
      predominantly believed that considerations about quality of life are most
      important. Quality of life and wellbeing were also frequently considered in both
      decisions to start/continue an intervention and decisions to forgo/withdraw an
      intervention. Seventy percent believed that people with ID should always be
      informed about interventions, and 61% would respect a refusal by the person. The
      family's wishes were explicitly considered more often than the wishes of the
      person with ID. CONCLUSION: Although respondents agree that the quality of life
      is highly important, the wishes of people with ID (especially of those with
      severe/profound ID) were often not considered in decisions about potentially
      burdensome medical interventions. PRACTICE IMPLICATIONS: To enhance the active
      involvement of people with ID in decision making we recommend that professionals
      integrate collaborative principles in decision making and make use of pictorial
      and easy reading resources.

PMID- 24938913
TI  - Reprogramming of mesenchymal stem cells by oncogenes.
AB  - Mesenchymal stem cells (MSCs) originate from embryonic mesoderm and give rise to
      the multiple lineages of connective tissues. Transformed MSCs develop into
      aggressive sarcomas, some of which are initiated by specific chromosomal
      translocations that generate fusion proteins with potent oncogenic properties.
      The sarcoma oncogenes typically prime MSCs through aberrant reprogramming. They
      dictate commitment to a specific lineage but prevent mature differentiation, thus
      locking the cells in a state of proliferative precursors. Deregulated expression
      of lineage-specific transcription factors and controllers of chromatin structure
      play a central role in MSC reprogramming and sarcoma pathogenesis. This suggests
      that reversing the epigenetic aberrancies created by the sarcoma oncogenes with
      differentiation-related reagents holds great promise as a beneficial addition to
      sarcoma therapies. 

PMID- 24938916
TI  - [Mother-infant dengue transmission during the 2009-2010 dengue epidemic: report
      of four cases].
AB  - The risks related to dengue virus infection during pregnancy have been
      increasingly better described over the past 10 years. The possibility of maternal
      fetal transmission is now recognized, but the diagnosis is still too late because
      of a wide range of clinical signs that the infected newborn child can present.
      From December 2009 to October 2010, Guadeloupe Island underwent an exceptional
      dengue epidemic. During this epidemic, at least four cases of vertical virus
      transmission were biologically proved. The purpose of this article is to describe
      the clinical aspects of these cases, some of which have rarely been described in
      this pathology. Of the four cases, one showed fetal growth restriction, one
      neonatal cholestasia, one twin pregnancy, and what seems to be the first case of
      hemophagocytic syndrome associated with a newborn child infected by this virus.
      Although the proportion of vertical transmission proved is low, compared with the
      number of adults affected during an epidemic, some severe cases urge us to be
      increasingly watchful with this emergent arbovirus, especially because its real
      incidence is still unknown.

PMID- 24938915
TI  - [Changes in bacterial meningitis in French children resulting from vaccination].
AB  - BACKGROUND: For the past 20 years, three vaccines against the three main
      bacterial species implicated in meningitis in children have been included in the
      French vaccine calendar: Haemophilus influenzae b in 1993, 7-valent pneumococcal
      conjugate vaccine (PCV7) in 2003 (replaced by 13-valent in 2010) and Neisseria
      meningitidis C in 2009. The French active surveillance network from the
      GPIP/ACTIV monitors the change in the epidemiological, clinical, and biological
      features of bacterial meningitis due to vaccine use. METHODS: Over a 12-year
      period, 233 pediatric wards working with 168 microbiology departments throughout
      France were asked to report all cases of bacterial meningitis. RESULTS: From
      January 2001 to December 2012, 4808 bacterial meningitis cases were reported.
      Between 2001 and 2012, the number of pneumococcal meningitis (PM) cases decreased
      by 23.4%, and by 32.2% for children less than 2 years old. During this period,
      the proportion of cases attributable to PCV7 and six additional PCV13 types
      decreased from 63.3% to 8.1% and 83.7% to 32.4%, respectively. In 2012, the main
      vaccine types (accounting for 25.8% of cases) were 7F (12.2%), 19A (6.8%), and
      19F (6.8%), and the most frequent non-vaccine types were 12F (14.9%), 24F
      (14.9%), 15B/C (6.8%), 22F (6.8%), and 10A (5.4%). In 2012, the rate of strains
      with decreased susceptibility to cefotaxime/ceftriaxone (MIC>0.5 MUg/mL)
      represented less than 3% of cases, with no identified resistant strain since 2010
      (MIC>2 MUg/mL). Between 2001 (n=67) and 2012 (n=9), the number of NmC meningitis
      cases decreased by 87%. CONCLUSION: With more than 4800 bacterial meningitis
      cases reported in 12 years, this nationwide survey provides essential information
      on the microbiological and clinical characteristics of bacterial meningitis
      (epidemiology or resistance data). These results could lead to changing
      antibiotic treatment of pneumococcal meningitis before the results of antibiotic
      susceptibility tests.

PMID- 24938914
TI  - High frequency stimulation extends the refractory period and generates axonal
      block in the rat hippocampus.
AB  - BACKGROUND: The therapeutic mechanisms of deep brain stimulations (DBS) are not
      fully understood. Axonal block induced by high frequency stimulation (HFS) has
      been suggested as one possible underlying mechanism of DBS. OBJECTIVE: To
      investigate the mechanism of the generation of HFS-induced axonal block. METHODS:
      High frequency pulse trains were applied to the fiber tracts of alveus and
      Schaffer collaterals in the hippocampal CA1 neurons in anaesthetized rats at 50,
      100 and 200 Hz. The amplitude changes of antidromic-evoked population spikes
      (APS) were measured to determine the degree of axonal block. The amplitude ratio
      of paired-pulse evoked APS was used to assess the changes of refractory period.
      RESULTS: There were two distinct recovery stages of axonal block following the
      termination of HFS. One frequency-dependent faster phase followed by another
      frequency-independent slower phase. Experiments with specially designed temporal
      patterns of stimulation showed that HFS produced an extension of the duration of
      axonal refractory period thereby causing a fast recovery phase of the axonal
      block. Thus, prolonged gaps inserted within HFS trains could eliminate the axonal
      block and induced large population spikes and even epileptiform activity in the
      upstream or downstream regions. CONCLUSIONS: Extension of refractory period plays
      an important role on HFS induced axonal block. Stimulation pattern with properly
      designed pauses could be beneficial for different requirements of excitation or
      inhibition in DBS therapies.

PMID- 24938917
TI  - [Let's stop proton pump inhibitor prescriptions for suspected GERD in non
      validated indications!].

PMID- 24938918
TI  - [Treatment of pneumococcal meningitis in children in 2014. Position statement of
      the French Group for Pediatric Infectious Diseases].

PMID- 24938919
TI  - [Deep venous thrombosis complications during infections in pediatric patients:
      analysis of a series of 24 cases].
AB  - Venous thromboembolism disease (VTE) is rare in children (5.3 of 10,000
      hospitalized children). However, morbidity and mortality are high, especially
      when the child is already suffering from severe sepsis. We report an analytical
      study of 24 cases of deep venous thrombosis occurring in children during
      infection, recorded at the Montpellier University Hospital between 1999 and 2009.
      Many parameters were studied in each population (age, sex, familial and personal
      history of thrombosis, history of thrombophilia, the presence of a venous
      catheter, a causative organism, time to onset of thrombus, topography of lesions,
      acquired abnormalities of hemostasis, and thrombosis prophylaxis). The children
      were aged from 1 day of life to 16 years. Thromboses occurred in two clinical
      contexts: "contact" thrombosis (which appeared near the infection) and
      disseminated thrombosis. This is an early complication because in most of the
      cases, it appeared in the first 10 days of sepsis. Infection and coagulation
      appear to be closely related and the states of latent or decompensated
      disseminated intravascular coagulation are common. Nevertheless, it is not
      possible to predict the occurence of a thrombotic event. The presence of risk
      factors (venous catheters, acquired thrombophilia, or constitutional
      thrombophilia) may increase the thrombogenic potential of the infection. VTE
      should always be suspected and sought in case of an unfavorable clinical course,
      and routine prophylaxis of thrombosis during sepsis should be discussed.

PMID- 24938920
TI  - Olanzapine treatment during pregnancy and breastfeeding: a chance for women with
      psychotic illness?

PMID- 24938921
TI  - Laboratory tests for assessing adaptability and stickiness of dental composites.
AB  - OBJECTIVE: Handling (stickiness, adaptability) of a dental composite does
      strongly influence quality and success of a dental restoration. The purpose was
      to develop an in vitro test, which allows for evaluating adaptability and
      stickiness. METHODS: 15 dentists were asked for providing individual assessment
      (school scores 1-6) of five dental composites addressing adaptability and
      stickiness. Composites were applied with a dental plugger (d=1.8 mm) in a class I
      cavity (human tooth 17). The tooth was fixed on a force gauge for simultaneous
      determination of application forces with varying storage (6/25 degrees C) and
      application temperatures (6/25 degrees C). On basis of these data tensile tests
      were performed with a dental plugger (application force 1N/2N; v=35 mm/min) on
      PMMA- or human tooth plates. Composite was dosed onto the tip of the plugger and
      applied. Application and unplugging was performed once and unplugging forces (UF)
      and length of the adhesive flags (LAF) were determined at different storage (6/25
      degrees C) and application temperatures (25/37 degrees C). Unplugging work (UW)
      was calculated from area of UF and LAF data. RESULTS: The individual assessment
      revealed significantly different temperature-dependent application forces between
      0.58 N and 2.23 N. Adaptability was assessed between 2.1 and 2.8 school scores.
      Stickiness varied significantly between the materials (scores: 2-3.2). UW
      differed significantly between the materials with values between 3.20 N mm and
      37.83 N mm. Between PMMA substrate or tooth slides and between 1N or 2N
      application force only small UW differences were found. SIGNIFICANCE: The
      presented in vitro unplugging work allows for an in vitro estimation of the
      handling parameters adaptability and stickiness.

PMID- 24938922
TI  - Proteoglycans affect monomer infiltration in the etch-and-rinse bonding
      technique.
AB  - OBJECTIVES: To identify proteoglycans (PGs) and collagen fibrils (CF) within
      human dentin by means of a dual immunofluorescent labeling technique and to
      investigate the monomer infiltration of two etch-and-rinse adhesives to tosyl
      phenylalanine chloromethyl-ketone (TPCK)-treated trypsin (TRY)-pretreated dentin.
      METHODS: Thirty-micrometer sections of middle coronal dentin were obtained and
      etched with 37% phosphoric acid gel for 15 s. After preconditioning with or
      without TRY digestion, the sections were subjected to dual immunofluorescent
      labeling and observed with a confocal laser scanning microscope (CLSM).
      Demineralized dentin matrixes treated with or without TRY were observed with
      field emission scanning electron microscope (FE-SEM). Two etch-and-rinse
      adhesives, Adper Single Bond 2 (SB) and Prime & Bond NT (PBNT), were applied to
      the dentin surfaces that were pretreated with or without TRY. The thickness of
      the hybrid layers was evaluated under confocal micro-Raman spectroscopy and
      analyzed with a two-way ANOVA. RESULTS: Green and red fluorescence was used to
      represent the PGs and the CF that were colocalized in the same section with
      different distributions. PGs were localized in the lumens of the dentin tubules
      and in peritubular dentin, while the type-I collagen fibrils were localized in
      intertubular dentin and peritubular dentin. After preconditioning with TRY
      digestion, the red fluorescence decreased or disappeared, the organic filaments
      in the lumens of the dentin tubules disappeared, the tubules were enlarged, and
      the hybrid layer thickness for adhesives bonded to the TRY-pretreated dentin
      surfaces were significantly increased (p<0.001 for both SB and PBNT).
      SIGNIFICANCE: The dual immunofluorescence labeling methodology can be used to
      study the human dentin matrix without decalcifying the entire dentin fragment.
      Proteoglycans were localized in the lumens of the dentin tubules and in
      peritubular dentin, which could depress the infiltration of the adhesive resin
      monomers. The use of TRY digestion increased the thickness of the hybrid layer
      created by the tested two-step etch-and-rinse adhesive.

PMID- 24938923
TI  - Contributions of stress corrosion and cyclic fatigue to subcritical crack growth
      in a dental glass-ceramic.
AB  - OBJECTIVE: The objective of this study was to test the following hypotheses: (1)
      both cyclic degradation and stress-corrosion mechanisms result in subcritical
      crack growth (SCG) in a fluorapatite glass-ceramic (IPS e.max ZirPress, Ivoclar
      Vivadent) and (2) there is an interactive effect of stress corrosion and cyclic
      fatigue to accelerate subcritical crack growth. METHODS: Rectangular beam
      specimens were fabricated using the lost-wax process. Two groups of specimens
      (N=30/group) with polished (15MUm) or air-abraded surface were tested under rapid
      monotonic loading. Additional polished specimens were subjected to cyclic loading
      at two frequencies, 2Hz (N=44) and 10Hz (N=36), and at various stress amplitudes.
      All tests were performed using a fully articulated four-point flexure fixture in
      deionized water at 37 degrees C. The SCG parameters were determined using the
      ratio of inert strength Weibull modulus to lifetime Weibull modulus. A general
      log-linear model was fit to the fatigue lifetime data including time to failure,
      frequency, peak stress, and the product of frequency and logarithm of stress in
      ALTA PRO software. RESULTS: SCG parameters determined were n=21.7 and A=4.99*10(
      5) for 2Hz, and n=19.1 and A=7.39*10(-6) for 10Hz. After fitting the general log
      linear model to cyclic fatigue data, the coefficients of the frequency term
      (alpha1), the stress term (alpha2), and the interaction term (alpha3) had
      estimates and 95% confidence intervals of alpha1=-3.16 (-15.1, 6.30), alpha2=
      21.2 (-34.9, -9.73), and alpha3=0.820 (-1.59, 4.02). Only alpha2 was
      significantly different from zero. SIGNIFICANCE: (1) Cyclic fatigue does not have
      a significant effect on SCG in the fluorapatite glass-ceramic evaluated and (2)
      there was no interactive effect between cyclic degradation and stress corrosion
      for this material.

PMID- 24938924
TI  - Biaxial flexure strength determination of endodontically accessed ceramic
      restorations.
AB  - OBJECTIVES: To report analytic solutions capable of identifying failure stresses
      from the biaxial flexure testing of geometries representative of endodontic
      access cavities prepared through dental restorative materials. METHODS: The ring
      on-ring biaxial flexure strength of annular discs with a central circular hole
      supported peripherally by a knife-edge support and loaded evenly at the upper
      edge of the central hole were solved using general expressions of deformations,
      moments and shears for flat plates of a constant thickness. To validate the
      solutions, finite element analyses were performed. A three-dimensional one
      quarter model of the test was generated using a linear P-code FEA software and
      the boundary conditions represented the experimental test configuration whereby
      symmetry planes defined the full model. To enable comparison of the maximum
      principal stresses with experimental derived data, three groups of nominally
      identical feldspathic ceramic disks (n=30) were fabricated. Specimens from Group
      A received a 4mm diameter representative endodontic access cavity and were tested
      in ring-on-ring. Group B and C specimens remained intact and were tested in ring
      on-ring and ball-on-ring, respectively, to give insight into strength scaling
      effects. Fractography was used to confirm failure origins, and statistical
      analysis of fracture strength data was performed using one-way ANOVAs (P<0.05)
      and a Weibull approach. RESULTS: The developed analytical solutions were
      demonstrated to deviate <1% from the finite element prediction in the
      configuration studied. Fractography confirmed the failure origin of tested
      samples to coincide with the predicted stress maxima and the area where fracture
      is observed to originate clinically. Specimens from the three experimental groups
      A-C exhibited different strengths which correlated with the volume scaling
      effects on measured strength. SIGNIFICANCE: The solutions provided will enable
      geometric and materials variables to be systematically studied and remove the
      need for load-to-failure 'crunch the crown' testing.

PMID- 24938925
TI  - Acoustic emission analysis of the effect of simulated pulpal pressure and cavity
      type on the tooth-composite interfacial de-bonding.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of in vitro pulpal
      pressure and cavity type on the tooth-composite bonding interface by means of
      acoustic emission (AE) analysis. METHODS: Classes I and II cavities on extracted
      third molars were prepared and assigned to four groups of seven teeth each: (1)
      direct composite restoration without simulated pulpal pressure (SPP) in class I
      cavity, (2) direct composite restoration with SPP in class I cavity, (3) direct
      composite restoration without SPP in class II cavity, (4) direct composite
      restoration with SPP in class II cavity. The teeth were restored with Filtek Z250
      composite and Adper Scotchbond Multi-Purpose adhesive system (3M ESPE, St. Paul,
      MN, USA). AE events were recorded for 2000s during light-curing. Groups 2 and 4
      were subjected to 20 cm H2O hydrostatic pressure throughout the procedures. The
      data were analyzed with two-way ANOVA. After the AE test, teeth were sectioned
      longitudinally in mesio-distal direction, the tooth-composite interface was
      examined using SEM. RESULTS: SPP in Groups 2 (4.57 +/- 1.40) and 4 (3.43 +/-
      1.13) yielded significantly higher AE events number than those of Groups 1 (3.43
      +/- 1.51) and 3 (1.71 +/- 0.95) where the SPP was not applied (p<0.05). The
      number of AE events of class I cavity in Groups 1 and 2 were significantly higher
      than those of class II cavity in Groups 3 and 4 (p<0.05). SEM examination showed
      that all groups had intact enamel-composite interface, while micro-gaps were
      observed at the dentin-composite interface, mainly at the pulpal floor of the
      cavity. The class I cavities with SPP in Group 2 showed wider gaps more
      frequently than class II cavities without SPP in Group 3. SIGNIFICANCE: The SPP
      and class I cavity with high C-factor triggered more AE events, confirming its
      negative impact on the bonding interface.

PMID- 24938926
TI  - Synthesis of antibacterial and radio-opaque dimethacrylate monomers and their
      potential application in dental resin.
AB  - OBJECTIVE: In this study, three dimethacrylate quaternary ammonium compounds N,N
      bis[2-(3-(methacryloyloxy)propanamido)ethyl]-N-methyldodecyl ammonium iodide
      (QADMAI-12), N,N-bis[2-(3-(methacryloyloxy)propanamido)ethyl]-N-methylhexadecyl
      ammonium iodide (QADMAI-16), and N,N-bis[2-(3-(methacryloyloxy)propanamido)ethyl]
      N-methyloctadectyl ammonium iodide (QADMAI-18) were synthesized and proposed to
      be used as antibacterial and radio-opaque agents in dental resin. METHODS: All
      QADMAIs were synthesized through a 2-steps reaction route, and their structures
      were confirmed by FT-IR and 1H NMR spectra. Antibacterial activities against
      Streptococcus mutans (S. mutans) of QADMAIs were measured by agar diffusion test.
      Each QADMAI was mixed with TEGDMA (50/50, w/w) and photoinitiation system (0.7
      wt% of CQ and 0.7 wt% of DMAEMA) to form resin system. Degree of monomer
      conversion (DC) was determined by FT-IR analysis. The flexural strength (FS) and
      modulus (FM) of the polymer were measured using a three-point bending set up.
      Radiograph was taken to determine the radio-opacity of the polymer, and aluminum
      step-wedge (0.5-4 mm) was used as calibration standard. Surface charge density
      was measured using fluorescein binding. A single-species biofilm model with S.
      mutans as the tests organism was used to evaluate the antibacterial property of
      the polymer. Bis-GMA/TEGDMA resin system was used as control material in all of
      the tests. RESULTS: FT-IR and 1H NMR spectra showed that the structures of
      QADMAIs were the same as designed. ANOVA analysis revealed that antibacterial
      activity of QADMAI decreased with the increasing of alkyl chain length (p<0.05).
      QADMAI containing polymers had higher DC (p<0.05) but lower FS and FM (p<0.05)
      than control polymer. Alkyl chain length had no influence on DC (p>0.05), but FS
      and FM of QADMAI-12 containing polymer were better than those of QADMAI-16 and
      QADMAI-18 containing polymers (p<0.05). QADMAI containing polymers had much
      better radio-opacity than control polymer (p<0.05), and the radio-opacity of
      polymer decreased with the increasing of alkyl chain length (p<0.05). All of
      QADMAIs containing polymers had higher surface charge density than control
      polymer (p<0.05), and surface charge densities of QADMAI-12 and QADMAI-16
      containing polymers were nearly the same (p>0.05) which were higher than that of
      QADMAI-18 containing polymer (p<0.05). All of QADMAI containing polymers had good
      inhibitory effect on biofilm formation. SIGNIFICANCE: QADMAIs had no miscibility
      problem with TEGDMA, and QADMAIs could endow dental resin with both antibacterial
      activity and radio-opacity. Formulation of QADMAI containing resin should be
      optimized in terms of mechanical stregth to satisfy the requirements of dental
      resin for clinical application.

PMID- 24938927
TI  - Effects of external pelvic compression on isokinetic strength of the thigh
      muscles in sportsmen with and without hamstring injuries.
AB  - OBJECTIVES: To investigate whether application of a pelvic compression belt
      affects isokinetic strength of the thigh muscles in sportsmen with and without
      hamstring injuries. DESIGN: Randomized crossover, cross-sectional. METHODS:
      Twenty sportsmen (age 22.0+/-1.5 years) with hamstring injuries (hamstring
      injured group) and 29 (age 23.5+/-1.5 years) without hamstring injuries (control
      group) underwent isokinetic testing of the thigh muscles. Testing included five
      reciprocal concentric quadriceps and hamstring contractions, and five eccentric
      hamstring contractions at an angular velocity of 60 degrees /s, with and without
      a pelvic compression belt in randomized order. The outcome measures were average
      torque normalized to bodyweight for terminal range eccentric hamstring
      contractions and peak torque normalized to bodyweight for concentric quadriceps,
      concentric hamstring and eccentric hamstring contractions. RESULTS: There was a
      significant increase in normalized average torque of eccentric hamstring
      contractions in the terminal range for both groups (p<=0.044) and normalized peak
      torque of eccentric hamstring contractions for injured hamstrings (p=0.025) while
      wearing the pelvic compression belt. No significant changes were found for other
      torque variables. Injured hamstrings were weaker than the contralateral uninjured
      hamstrings during terminal range eccentric hamstring (p=0.040), and concentric
      hamstring (p=0.020) contractions recorded without the pelvic compression belt.
      However, no between-group differences were found for any of the investigated
      variables. CONCLUSION: Wearing the pelvic compression belt appears to have a
      facilitatory effect on terminal range eccentric hamstring strength in sportsmen
      with and without hamstring injuries. Future investigations should ascertain
      whether there is a role for using a pelvic compression belt for rehabilitation of
      hamstring injuries.

PMID- 24938928
TI  - Optical dosimetry of radiotherapy beams using Cherenkov radiation: the
      relationship between light emission and dose.
AB  - Recent studies have proposed that light emitted by the Cherenkov effect may be
      used for a number of radiation therapy dosimetry applications. There is a
      correlation between the captured light and expected dose under certain
      conditions, yet discrepancies have also been observed and a complete examination
      of the theoretical differences has not been done. In this study, a fundamental
      comparison between the Cherenkov emission and absorbed dose was explored for x
      ray photons, electrons, and protons using both a theoretical and Monte Carlo
      based analysis. Based on the findings of where dose correlates with Cherenkov
      emission, it was concluded that for x-ray photons the light emission would be
      optimally suited for narrow beam stereotactic radiation therapy and surgery
      validation studies, for verification of dynamic intensity-modulated and
      volumetric modulated arc therapy treatment plans in water tanks, near
      monoenergetic sources (e.g., Co-60 and brachy therapy sources) and also for
      entrance and exit surface imaging dosimetry of both narrow and broad beams. For
      electron use, Cherenkov emission was found to be only suitable for surface
      dosimetry applications. Finally, for proton dosimetry, there exists a fundamental
      lack of Cherenkov emission at the Bragg peak, making the technique of little use,
      although post-irradiation detection of light emission from radioisotopes could
      prove to be useful. 

PMID- 24938929
TI  - Beta-catenin regulates NF-kappaB activity and inflammatory cytokine expression in
      bronchial epithelial cells treated with lipopolysaccharide.
AB  - In the present study, we demonstrate that lipopolysaccharide (LPS) induces the
      expression of inflammatory cytokines, including interleukin (IL)-6, IL-8, IL
      1beta, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein
      (MCP)-1 in BEAS-2B human bronchial epithelial cells in a dose- and time-dependent
      manner. This increase was accompanied by an increased activity of nuclear factor
      (NF)-kappaB. When the expression of beta-catenin was analyzed following treatment
      with LPS, the mRNA level was unaltered; however, the beta-catenin protein levels
      increased with a decrease in phosphorylation at the serine 33/37 residues.
      Nuclear beta-catenin protein levels also increased along with the reporter
      activity of a beta-catenin-responsive TOPFlash vector. To elucidate the
      regulatory role of beta-catenin in the LPS-induced inflammatory response of
      bronchial epithelial cells, beta-catenin production was knocked down using siRNA.
      Our results revealed that beta-catenin protein levels and TOPFlash vector
      reporter activity were reduced to basal levels by siRNA transfection. In this
      experimental condition, NF-kappaB activity, measured by enzyme-linked
      immunosorbent assay (ELISA), electrophoretic mobility shift assay (EMSA) and an
      NF-kappaB responsive reporter assay, was reduced to basal levels. Similarly, LPS
      induced inflammatory cytokine expression was reduced almost to basal levels
      following transfection with beta-catenin siRNA. These results demonstrate that
      beta-catenin positively regulates NF-kappaB activity, as well as the expression
      of inflammatory cytokines in the inflammatory response of LPS-treated bronchial
      epithelial cells.

PMID- 24938930
TI  - On the permanent hip-stabilizing effect of atmospheric pressure.
AB  - Hip joint dislocations related to total hip arthroplasty (THA) are a common
      complication especially in the early postoperative course. The surgical approach,
      the alignment of the prosthetic components, the range of motion and the muscle
      tone are known factors influencing the risk of dislocation. A further factor that
      is discussed until today is atmospheric pressure which is not taken into account
      in the present THA concepts. The aim of this study was to investigate the impact
      of atmospheric pressure on hip joint stability. Five joint models (O 28-44 mm),
      consisting of THA components were hermetically sealed with a rubber capsule,
      filled with a defined amount of fluid and exposed to varying ambient pressure.
      Displacement and pressure sensors were used to record the extent of dislocation
      related to intraarticular and ambient pressure. In 200 experiments spontaneous
      dislocations of the different sized joint models were reliably observed once the
      ambient pressure was lower than 6.0 kPa. Increasing the ambient pressure above
      6.0 kPa immediately and persistently reduced the joint models until the ambient
      pressure was lowered again. Displacement always exceeded half the diameter of the
      joint model and was independent of gravity effects. This experimental study gives
      strong evidence that the hip joint is permanently stabilized by atmospheric
      pressure, confirming the theories of Weber and Weber (1836). On basis of these
      findings the use of larger prosthetic heads, capsular repair and the deployment
      of an intracapsular Redon drain are proposed to substantially decrease the risk
      of dislocation after THA.

PMID- 24938931
TI  - Latinos' Access to Online and Formal Mental Health Support.
AB  - Research on mental health services disparities affecting minority populations of
      the USA tends to neglect online mental health support (OMHS). The main objective
      of this study was to investigate online mental health support and help-seeking of
      Latino citizens living in US communities by estimating associations linking OMHS
      with a selection of individual and community variables. In addition, the extent
      to which unmet mental health treatment needs among adults are associated with key
      variables was examined. Variables of interest included economic resources, health
      insurance and coverage, confidentiality, perceived stigma, and accessibility.
      Data are from 39,630 Latino adult participants in the National Surveys on Drug
      Use and Health (NSDUH), 2004-2010. Results indicate that for every 10,000 US
      Latino adults, fewer than 25 individuals received recent OMHS, as compared to a
      recently published estimate of 270-330 per 10,000 for the US population
      generally. Among Latinos with self-described unmet mental health needs, an
      estimated 40% identified cost of treatment as a prominent barrier that explained
      why they had not received formal mental health treatment services. Research and
      policy health disparities implications are discussed. 

PMID- 24938933
TI  - Homogeneous liquid-liquid extraction of neodymium(III) by choline
      hexafluoroacetylacetonate in the ionic liquid choline
      bis(trifluoromethylsulfonyl)imide.
AB  - The ionic liquid choline bis(trifluoromethylsulfonyl)imide, [Chol][Tf2N], was
      used for the extraction of neodymium(III), in combination with choline
      hexafluoroacetylacetonate, [Chol][hfac], as the extractant. The binary mixture of
      [Chol][Tf2N] and water shows temperature-dependent phase behavior, with an upper
      critical solution temperature of 72  degrees C. A novel extraction technique,
      homogeneous liquid-liquid extraction (HLLE), was applied to this solvent system.
      HLLE is based on the use of thermomorphic solvent mixtures and has the advantage
      of forming a homogeneous phase during mixing. Extraction is not kinetically
      hindered by an interface and the extraction equilibrium is reached faster than in
      the case of heterogeneous mixing in conventional solvent extraction. Several
      extraction parameters were studied for the extraction of neodymium(III) with
      [Chol][hfac]: temperature, pH, extractant concentration and loading of the ionic
      liquid phase. A speciation study was performed to determine the stoichiometry of
      the extracted neodymium(III) complex and a plausible extraction mechanism is
      proposed. Neodymium is extracted as a tetrakis hexafluoroacetylacetonate complex
      with one choline cation as counter ion. The crystal structure of the extracted
      complex showed the presence of a coordination bond between the choline counter
      ion and the neodymium(III) center, resulting in a coordination number of nine.
      The stripping of the loaded neodymium and the influence of acid and extractant
      concentrations on the phase behavior of the [Chol][Tf2N]-H2O system were
      investigated.

PMID- 24938932
TI  - Affordable Care Act and behavioral health services: special section editor's
      note.

PMID- 24938934
TI  - Cost-effectiveness of the endoscopic versus microscopic approach for pituitary
      adenoma resection.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the cost-effectiveness of an endoscopic versus
      microscopic approach to pituitary adenoma resection. STUDY DESIGN: Markov
      decision tree economic evaluation. METHODS: An economic evaluation using a Markov
      decision tree model was performed. The economic perspective was that of the
      healthcare third-party payer. Effectiveness and probability data were obtained
      from a single meta-analysis of 38 studies. Costs were obtained from the
      Healthcare Cost and Utilization Project database and wholesale pharmaceutical
      pricing. Multiple sensitivity analyses were performed including a probabilistic
      sensitivity analysis. Comparative treatment groups were: 1) endoscopic approach
      and 2) microscopic approach to pituitary adenoma resection. The primary outcome
      was cost per quality-adjusted life year (QALY). The time horizon was 25 years,
      and costs were discounted at a rate of 3.5%. RESULTS: The endoscopic approach
      cost a total of $17,244.63 and produced a total of 24.30 QALYs. The microscopic
      approach cost a total of $23,756.60 and produced a total of 24.20 QALYs. In the
      reference case, the endoscopic approach was a dominant intervention (both less
      costly and more effective); therefore, an incremental cost-effectiveness ratio
      was not calculated. The sensitivity analysis demonstrated 79% certainty that the
      endoscopic approach is the cost-effective decision, at a willingness to pay
      threshold of $50,000 per QALY. CONCLUSIONS: This economic evaluation suggests
      that the endoscopic approach is the more cost-effective intervention compared to
      the microscopic approach for patients requiring a pituitary adenoma resection.

PMID- 24938935
TI  - Identifying patient safety problems during team rounds: an ethnographic study.

PMID- 24938936
TI  - Bedoradrine for treating asthma and chronic obstructive pulmonary disease.
AB  - INTRODUCTION: In severe asthma attacks or in severe chronic obstructive pulmonary
      disease (COPD) exacerbations, inhaled short-acting bronchodilators, such as
      salbutamol (albuterol), terbutaline or ipratropium, often have a limited
      effectiveness due to significantly impaired ventilation. For these reasons, the
      use of a systemic bronchodilator medication might be more appropriate as
      therapeutic options. However, such formulations, especially salbutamol, are
      usually, and unfortunately, associated with a high risk of cardiovascular events.
      For this reason, they are only seldom used, especially in the case of paediatric
      populations. AREAS COVERED: This drug evaluation paper reviews the potential
      therapeutic agent bedoradrine, an ultraselective beta2 agonist, which is
      currently under development for treating exacerbated asthma and COPD. The article
      includes a review of both in vitro and in vivo studies as well as a review of the
      pharmacokinetics, efficacy, safety and tolerability. EXPERT OPINION: The
      intravenous use of bedoradrine has demonstrated promising preliminary efficacy in
      existing clinical trials for exacerbated asthma. However, the efficacy of
      bedoradrine is still uncertain in exacerbated COPD. Further clinical studies
      should assess the efficacy and safety of bedoradrine as an add-on therapy to
      usual standardised approach and exacerbation-related variables should be used as
      outcome measures.

PMID- 24938938
TI  - Double standard on pay dishonours profession.

PMID- 24938937
TI  - Partial breast irradiation for early breast cancer.
AB  - BACKGROUND: Breast conserving therapy for women with breast cancer consists of
      local excision of the tumour (achieving clear margins) followed by radiation
      therapy (RT). RT is given to sterilize tumour cells that may remain after surgery
      to decrease the risk of local tumour recurrence. Most true recurrences occur in
      the same quadrant as the original tumour. Whole breast RT may not protect against
      the development of a new primary cancer developing in other quadrants of the
      breast. In this Cochrane Review, we investigated the role of delivering radiation
      to a limited volume of the breast around the tumour bed (partial breast
      irradiation: PBI) sometimes with a shortened treatment duration (accelerated
      partial breast irradiation: APBI). OBJECTIVES: To determine whether PBI/APBI is
      equivalent to or better than conventional or hypofractionated WBRT after breast
      conservation therapy for early-stage breast cancer. SEARCH METHODS: We searched
      the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL
      (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11
      April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we
      searched the International Standard Randomised Controlled Trial Number Register,
      the World Health Organization's International Clinical Trials Registry Platform
      (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22
      April 2014). We searched for grey literature: Open Grey (23 April 2014),
      reference lists of articles, a number of conference proceedings and published
      abstracts, and did not apply any language restrictions. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) without confounding and evaluating
      conservative surgery plus PBI/APBI versus conservative surgery plus whole breast
      RT. We included both published and unpublished trials. DATA COLLECTION AND
      ANALYSIS: Three review authors (ML, DF and BH) performed data extraction and
      resolved any disagreements through discussion. We entered data into Review
      Manager for analysis. BH and ML assessed trials, graded the methodological
      quality using Cochrane's Risk of Bias tool and resolved any disagreements through
      discussion. MAIN RESULTS: We included four RCTs that had 2253 women. Two older
      trials examined RT techniques which do not reflect current practice and one trial
      had a short follow-up. We downgraded the quality of the evidence for our key
      outcomes due to risk of bias. Taken together with other GRADE recommendations,
      the quality of evidence for our outcomes was very low to low. For the comparison
      of partial breast irradiation/accelerated breast irradiation (PBI/APBI) with
      whole breast irradiation (WBRT), local recurrence-free survival appeared worse
      (Hazard Ratio (HR) 1.74, 95% confidence interval (CI) 1.23 to 2.45; three trials,
      1140 participants, very low quality evidence). Cosmesis appeared improved with
      PBI/APBI in a single trial (OR 0.40, 95% CI 0.23 to 0.72; one trial, 241
      participants, very low quality evidence), but late toxicity (telangiectasia OR
      4.41, 95% CI 3.21 to 6.05; very low quality evidence, 708 participants) and
      subcutaneous fibrosis (OR 4.27, 95% CI 3.04 to 6.01; one trial, 710 participants,
      very low quality evidence) appeared increased in another trial. We found no clear
      evidence of a difference for the comparison of PBI/APBI versus WBRT for the
      outcomes of: overall survival (HR 0.99, 95% CI 0.83 to 1.18; three trials, 1140
      participants, very low quality evidence), cause-specific survival (HR 0.95, 95%
      CI 0.74 to 1.22; two trials, 966 participants, low evidence quality), distant
      metastasis-free survival (HR 1.02, 95% CI 0.81 to 1.28; 1140 participants, low
      quality evidence), subsequent mastectomy rate (OR 0.20, 95% CI 0.01 to 4.21; 258
      participants, low quality evidence) and relapse-free survival (HR 0.99, 95% CI
      0.53 to 1.85; 258 participants, low quality evidence). We found no data for the
      outcomes of acute toxicity, new ipsilateral breast primaries, costs, quality of
      life or consumer preference. AUTHORS' CONCLUSIONS: The limitations of the data
      currently available mean that we cannot make definitive conclusions about the
      efficacy and safety or ways to deliver of PBI/APBI. We await completion of
      ongoing trials.

PMID- 24938940
TI  - Employers 'raid' poorer countries after five years of training cuts.

PMID- 24938939
TI  - Pay strike would leave patients in the lurch, Carter tells RCN congress.

PMID- 24938941
TI  - Chief executive pay hikes 'a kick in the teeth for nurses', says RCN.

PMID- 24938942
TI  - District nursing could face extinction by 2025.

PMID- 24938943
TI  - NICE told to beef up its guidance on safe staffing.

PMID- 24938944
TI  - Staff demonstrate outside congress to highlight NHS pay inequalities.

PMID- 24938945
TI  - Alert issued over potentially fatal use of suction drains.

PMID- 24938947
TI  - Tracheostomy training needed.

PMID- 24938948
TI  - Leg club staff showcase their work.

PMID- 24938949
TI  - Stroke nurses to take part in global trial of patient positioning policies.

PMID- 24938950
TI  - Nursing celebrated in Queen's birthday honours.

PMID- 24938951
TI  - 'Nurses are not just there for when patients are ill'.

PMID- 24938953
TI  - Employers welcome guidance on performance-related pay systems.

PMID- 24938954
TI  - Wright Angle - Stephen Wright's monthly take on nursing in the news: beware those
      who claim our NHS is unaffordable.

PMID- 24938960
TI  - Bowel cancer.

PMID- 24938961
TI  - Delivering best care in war and peace.
AB  - Col Alan Finnegan, the fi rst Ministry of Defence professor of nursing, is
      driving forward research into preparing nurses for deployment and ensuring they
      deliver the best care possible in war and peace. Research topics range from the
      role of autonomous practitioners to the effects on soldiers of injuries to their
      genitalia.

PMID- 24938962
TI  - Honesty will always be the best policy.
AB  - Under the draft code nurses and midwives must comply with a proactive duty of
      candour, informing patients and relatives when care may have caused harm, acting
      immediately to put things right, and responding honestly to complaints and
      investigations.

PMID- 24938975
TI  - Personal healthcare budgets fail to meet 'the general good'.

PMID- 24938976
TI  - Care assistant regulation would help improve care home quality.

PMID- 24938977
TI  - Decision to spell out basic care duties in new code is patronising.

PMID- 24938978
TI  - Using the carrot and stick approach to improve care is not the solution.

PMID- 24938981
TI  - Help us in our ambition to end FGM in the UK within a generation.

PMID- 24938980
TI  - Government's failure to legislate puts unsustainable onus on NMC.

PMID- 24938982
TI  - Rectus sheath catheter infusions for post-operative pain management.
AB  - Managing pain following major abdominal surgery remains a challenge.
      Traditionally, patient-controlled analgesia (PCA) or epidural analgesia have been
      used, which have improved post-operative pain and the patient experience, but
      have presented some problems in recovery. PCA can cause adverse effects,
      including sedation, nausea, vomiting, and prolonged gastric ileus. While
      epidurals do have some advantages over PCA, there are risks involved related to
      catheter insertion and adverse effects, such as hypotension and motor blocks
      which limit mobility. This article examines rectus sheath catheter infusions, a
      relatively new and alternative technique to epidural analgesia, and presents some
      early audit data related to pain scores, analgesic use and mobility. 

PMID- 24938983
TI  - Involving service users in delivering alcohol addiction therapy.
AB  - Involving and empowering people who use health services, and taking their
      experiences into account, has evolved from being considered good practice to
      being duties of the NHS. However, evidence suggests that the rate of progress and
      change has been slow, despite the constant emphasis on the merits of involving
      and engaging the public and patients. This article, written in collaboration with
      two service users, reports on efforts by nursing staff working in alcohol
      addiction to involve service users in setting up and managing the self-management
      and recovery training initiative at the Brian Hore Unit, part of the Manchester
      Mental Health and Social Care Trust. The article aims to encourage healthcare
      professionals to appreciate the benefits of proactive patient and public
      involvement for their organisations and for those who get involved. 

PMID- 24938984
TI  - Hypertension: diagnosis, assessment and management.
AB  - Hypertension is a serious and common condition, the prevalence of which is set to
      rise given the increase in the ageing population, sedentary lifestyles and
      obesity. This article reviews the management of primary hypertension in adults,
      with reference to the National Institute for Health and Care Excellence
      guidelines. Diagnosis using clinic, ambulatory and home blood pressure (BP)
      monitoring, risk factors , BP targets, lifestyle advice, drug treatment and
      patient education are also discussed. 

PMID- 24938985
TI  - Deep vein thrombosis.

PMID- 24938986
TI  - Inspiring a generation.

PMID- 24938987
TI  - Devolution into the bargain.

PMID- 24938989
TI  - Student life - A wealth of possibilities.

PMID- 24938991
TI  - Design of parallel transmission pulses for simultaneous multislice with explicit
      control for peak power and local specific absorption rate.
AB  - PURPOSE: To design parallel transmit (pTx) simultaneous multislice (SMS) spokes
      pulses with explicit control for peak power and local and global specific
      absorption rate (SAR). METHODS: We design SMS pTx least-squares and magnitude
      least squares spokes pulses while constraining local SAR using the virtual
      observation points (VOPs) compression of SAR matrices. We evaluate our approach
      in simulations of a head (7T) and a body (3T) coil with eight channels arranged
      in two z-rows. RESULTS: For many of our simulations, control of average power by
      Tikhonov regularization of the SMS pTx spokes pulse design yielded pulses that
      violated hardware and SAR safety limits. On the other hand, control of peak power
      alone yielded pulses that violated local SAR limits. Pulses optimized with
      control of both local SAR and peak power satisfied all constraints and therefore
      had the best excitation performance under limited power and SAR constraints.
      These results extend our previous results for single slice pTx excitations but
      are more pronounced because of the large power demands and SAR of SMS pulses.
      CONCLUSIONS: Explicit control of local SAR and peak power is required to generate
      optimal SMS pTx excitations satisfying both the system's hardware limits and
      regulatory safety limits.

PMID- 24938992
TI  - Expression and effect of CXCL14 in colorectal carcinoma.
AB  - Chemokines are important in the proliferation and metastasis of tumors. CXCL14 is
      a member of the CXCL chemokine family and exhibits various expression patterns in
      different types of tumor, even those tumors that occur in the same type of
      tissue. The expression of CXCL14 and its clinical significance in colorectal
      carcinoma are unclear. In the present study, the expression levels of CXCL14 in
      colorectal carcinoma and adjacent normal tissues were detected using reverse
      transcription-quantitative polymerase chain reaction and immunohistochemistry.
      Kaplan-Meier survival curves and the Cox regression model were applied to
      evaluate the clinical significance of the expression levels of CXCL14 in
      colorectal carcinoma compared with those in normal tissues. To investigate the
      effects at a cellular level, a replication-defective lentivirus overexpressing
      CXCL14 was constructed and transfected into HT29 colorectal carcinoma cells. The
      effect of CXCL14 on the proliferation of colorectal carcinoma cells and the
      change in cell cycle distributions were investigated using a cell counting kit-8
      assay and flow cytometry, respectively. Results of the current study indicated
      that the expression levels of CXCL14 mRNA and protein in colorectal carcinoma
      were markedly reduced compared with levels in normal tissues (P<0.05). The
      clinical correlation analysis suggested that downregulation of CXCL14 expression
      in tumors was associated with lymph metastasis, tumor location, and
      clinicopathological stage (P<0.05). Kaplan-Meier survival analysis revealed that
      downregulation of CXCL14 expression was correlated with a poor prognosis
      (P<0.01). Overexpression of CXCL14 by lentiviral transfection produced an
      inhibitory effect on cell proliferation by arresting the cell cycle in the G1
      stage. The data of the current study suggest that CXCL14 may be involved in the
      development and progression of colorectal carcinoma, and may act directly as a
      potential cancer suppressor gene. The level of CXCL14 expression may be a
      valuable adjuvant parameter in predicting the prognosis of colorectal carcinoma
      and may be a potential therapeutic target. 

PMID- 24938993
TI  - Dopaminergic modulation of resting-state functional connectivity in de novo
      patients with Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by degenerative changes of nigral
      dopamine neurons, resulting in the dopaminergic denervation of the striatum.
      Resting state networks studies have demonstrated that dopamine modulates distinct
      network connectivity patterns in both a linear and a nonlinear fashion, but
      quantitative analyses of dopamine-dependent functional connectivity secondary to
      PD pathology were less informative. In the present study, we performed a
      correlation analysis between striatal dopamine levels assessed quantitatively by
      FP-CIT positron emission tomography imaging and resting-state functional
      connectivity in 23 drug naive de novo patients with PD to elucidate dopamine
      dependent functional networks. The major finding is that the patterns of dopamine
      dependent positive functional connectivity varied depending on the location of
      striatal seeds. Dopamine-dependent functional connectivity with the caudate
      predominantly overlay pericentral cortical areas, whereas dopamine-dependent
      structures functionally connected with the posterior putamen predominantly
      involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine
      dependent cortical region that was positively connected with the anterior and
      posterior putamen. On the other hand, cortical areas where functional
      connectivity from the posterior cingulate was negatively correlated with
      dopaminergic status in the posterior putamen were localized in the left anterior
      prefrontal area and the parietal area. Additionally, functional connectivity
      between the anterior putamen and mesiofrontal areas was negatively coupled with
      striatal dopamine levels. The present study demonstrated that dopamine-dependent
      functional network connectivity secondary to PD pathology mainly exhibits a
      consistent pattern, albeit with some variation. These patterns may reflect the
      diverse effects of dopaminergic medication on parkinsonian-related motor and
      cognitive performance.

PMID- 24938995
TI  - Increased power generation from primary sludge in microbial fuel cells coupled
      with prefermentation.
AB  - Raw primary sludge and the prefermentation liquor (PL) of primary sludge were
      used to generate electricity in single-chambered air-cathode microbial fuel cells
      (MFCs). The MFCs treating the primary sludge produced 0.53 V and 370 mW/m(2) for
      the maximum potential and power density, respectively. In the primary sludge-fed
      MFCs, only 5 % of the total energy production was produced from direct
      electricity generation, whereas 95 % of that resulted from the conversion of
      methane to electricity. MFCs treating the PL generated the maximum potential of
      0.58 V and maximum power density of 885 mW/m(2), respectively. In the energy
      production analysis, direct electricity production (1,921 Wh/kg TCODrem) in the
      MFCs treating the PL was much higher than that of the primary sludge-fed MFC (138
      Wh/kg TCODrem). Volatile suspended solids during 10 days were reduced to 18.3 and
      38 % in the primary sludge-fed MFCs and prefermentation reactor, respectively.
      These findings suggest that a two-stage process including prefermentation and
      MFCs is of great benefit on sludge reduction and higher electricity generation
      from primary sludge. 

PMID- 24938994
TI  - Kinetics of sucrose conversion to fructo-oligosaccharides using enzyme
      (invertase) under free condition.
AB  - The study reports the synthesis of fructo-oligosaccharide (FOS) from sucrose
      using invertase derived from Saccharomyces cerevisiae. The reaction was conducted
      in a batch mode under free enzyme condition. Fructo-oligosaccharide formation was
      detected at a high sucrose concentration of over 200 g/L. The investigation was
      extended to study the effect of different parameters such as initial sucrose
      concentration (ISC), pH, and enzyme concentration. A maximum FOS yield of 10 %
      (dry basis) was observed using 525 g/L of ISC, with 6 U/mL of the enzyme, and pH
      5.5 at 40  degrees C. 1-Kestose was the major product of among different forms of
      FOS. The FOS yield increased with an increase in sucrose concentration up to 525
      g/L, beyond which it started to decrease. However, the maximum FOS yield was not
      affected by the increasing concentration of the enzyme beyond a certain level (2
      U/mL). Furthermore, the activity of enzyme slightly increased with an increase in
      the pH up to 6, and thereafter it declined. Addition of glucose decreased the FOS
      yield because of enzyme inhibition. A five-step, ten-parameter model was
      developed, for which the simulation was performed in COPASI. The results
      predicted by the model were consistent with the experimental data. 

PMID- 24938996
TI  - Iodine-catalyzed aromatization of tetrahydrocarbazoles and its utility in the
      synthesis of glycozoline and murrayafoline A: a combined experimental and
      computational investigation.
AB  - A new protocol for the aromatization of tetrahydrocarbazoles has been achieved
      using a catalytic amount of iodine, giving high yields. The role of iodine in the
      aromatization has been explained by DFT, and its wide scope is extended to the
      total synthesis of glycozoline and murrayafoline A. This method has proven to be
      tolerant of a broad range of functional groups. 

PMID- 24938990
TI  - Microenvironmental Influences on Metastasis Suppressor Expression and Function
      during a Metastatic Cell's Journey.
AB  - Metastasis is the process of primary tumor cells breaking away and colonizing
      distant secondary sites. In order for a tumor cell growing in one
      microenvironment to travel to, and flourish in, a secondary environment, it must
      survive a series of events termed the metastatic cascade. Before departing the
      primary tumor, cells acquire genetic and epigenetic changes that endow them with
      properties not usually associated with related normal differentiated cells. Those
      cells also induce a subset of bone marrow-derived stem cells to mobilize and
      establish pre-metastatic niches [1]. Many tumor cells undergo epithelial-to
      mesenchymal transition (EMT), where they transiently acquire morphologic changes,
      reduced requirements for cell-cell contact and become more invasive [2]. Invasive
      tumor cells eventually enter the circulatory (hematogenous) or lymphatic systems
      or travel across body cavities. In transit, tumor cells must resist anoikis,
      survive sheer forces and evade detection by the immune system. For blood-borne
      metastases, surviving cells then arrest or adhere to endothelial linings before
      either proliferating or extravasating. Eventually, tumor cells complete the
      process by proliferating to form a macroscopic mass [3].Up to 90 % of all cancer
      related morbidity and mortality can be attributed to metastasis. Surgery manages
      to ablate most primary tumors, especially when combined with chemotherapy and
      radiation. But if cells have disseminated, survival rates drop precipitously.
      While multiple parameters of the primary tumor are predictive of local or distant
      relapse, biopsies remain an imperfect science. The introduction of molecular and
      other biomarkers [4, 5] continue to improve the accuracy of prognosis. However,
      the invasive procedure introduces new complications for the patient. Likewise,
      the heterogeneity of any tumor population [3, 6, 7] means that sampling error
      (i.e., since it is impractical to examine the entire tumor) necessitates further
      improvements.In the case of breast cancer, for example, women diagnosed with
      stage I diseases (i.e., no evidence of invasion through a basement membrane)
      still have a ~30 % likelihood of developing distant metastases [8]. Many
      physicians and patients opt for additional chemotherapy in order to "mop up"
      cells that have disseminated and have the potential to grow into macroscopic
      metastases. This means that ~ 70 % of patients receive unnecessary therapy, which
      has undesirable side effects. Therefore, improving prognostic capability is
      highly desirable.Recent advances allow profiling of primary tumor DNA sequences
      and gene expression patterns to define a so-called metastatic signature [9-11],
      which can be predictive of patient outcome. However, the genetic changes that a
      tumor cell must undergo to survive the initial events of the metastatic cascade
      and colonize a second location belie a plasticity that may not be adequately
      captured in a sampling of heterogeneous tumors. In order to tailor or personalize
      patient treatments, a more accurate assessment of the genetic profile in the
      metastases is needed. Biopsy of each individual metastasis is not practical,
      safe, nor particularly cost-effective. In recent years, there has been a
      resurrection of the notion to do a 'liquid biopsy,' which essentially involves
      sampling of circulating tumor cells (CTC) and/or cell free nucleic acids (cfDNA,
      including microRNA (miRNA)) present in blood and lymph [12-16].The rationale for
      liquid biopsy is that tumors shed cells and/or genetic fragments into the
      circulation, theoretically making the blood representative of not only the
      primary tumor but also distant metastases. Logically, one would predict that the
      proportion of CTC and/or cfDNA would be proportionate to the likelihood of
      developing metastases [14]. While a linear relationship does not exist, the
      information within CTC or cfDNA is beginning to show great promise for enabling a
      global snapshot of the disease. However, the CTC and cfDNA are present at
      extremely low levels. Nonetheless, newer technologies capture enough material to
      enrich and sequence the patient's DNA or quantification of some biomarkers.Among
      the biomarkers showing great promise are metastasis suppressors which, by
      definition, block a tumor cell's ability to complete the metastatic process
      without prohibiting primary tumor growth [17]. Since the discovery of the first
      metastasis suppressor, Nm23, more than 30 have been functionally characterized.
      They function at various stages of the metastatic cascade, but their mechanisms
      of action, for the most part, remain ill-defined. Deciphering the molecular
      interactions of functional metastasis suppressors may provide insights for
      targeted therapies when these regulators cease to function and result in
      metastatic disease.In this brief review, we summarize what is known about the
      various metastasis suppressors and their functions at individual steps of the
      metastatic cascade (Table 1). Some of the subdivisions are rather arbitrary in
      nature, since many metastasis suppressors affect more than one step in the
      metastatic cascade. Nonetheless what emerges is a realization that metastasis
      suppressors are intimately associated with the microenvironments in which cancer
      cells find themselves [18]. 

PMID- 24938997
TI  - Predominant and secondary pollen botanical origins influence the carotenoid and
      fatty acid profile in fresh honeybee-collected pollen.
AB  - Total and individual carotenoids, fatty acid composition of total lipids, and
      main lipid classes of 16 fresh bee-collected pollen samples from Romania were
      determined by high-performance liquid chromatography with photodiode array
      detection and capillary gas chromatography with mass detection. Analyzed samples
      were found rich in lutein, whereas beta-criptoxanthin and beta-carotene were
      present in a wide range of amounts correlated with predominant botanical origin
      of the samples. High amounts of lutein were correlated with the presence of
      Callendula officinalis, Taraxacum officinale and Anthylis sp. The highest amount
      of total lipids was found in samples where pollen from Brassica sp. was
      predominant. Lipid classes were dominated by polyunsaturated fatty acids.
      Saturated fatty acids were determined in variable amounts. Lipid and carotenoid
      contents present great variability, explained by the various botanical species
      present in the samples. 

PMID- 24938998
TI  - 'The more you link, the more you risk ...' - a focus group study exploring views
      about data linkage for pharmacovigilance.
AB  - AIMS: The aim of this study was to assess opinions of frontline healthcare
      professionals on the linking of routinely collected national (Scottish)
      paediatric data for the purpose of identifying earlier signals of adverse drug
      reactions. METHODS: Stratified purposive sampling led to profession-specific
      focus groups with pharmacists, nurses and medical doctors from primary and
      secondary care in different Scottish Health Boards. A topic guide was used to
      explore the proposed data linkage of routinely collected paediatric data.
      Discussions were audio recorded and transcribed verbatim. Transcripts were
      analysed using a framework approach to identify themes. Ethical approval was
      obtained from the North of Scotland Research Ethics Service. RESULTS: Six focus
      groups were conducted in 2011 with 22 participants. Views of the proposed data
      linkage were generally positive. Several issues were identified, including lack
      of clarity on data ownership and concerns about diversion of funding. Identified
      issues were at a practical rather than a strategic level. CONCLUSIONS: This study
      identified that professional stakeholder groups are likely to find linkage of
      paediatric patient data acceptable. Barriers identified could be addressed. Focus
      group participants commented on the importance of informing patients and members
      of the public about the benefits of linking healthcare data. These findings
      clarify the steps that should be taken to ensure the acceptability of data
      linkage for pharmacovigilance.

PMID- 24938999
TI  - A potential pathogenic factor from Mycoplasma hominis is a TLR2-dependent,
      macrophage-activating, P50-related adhesin.
AB  - PROBLEM: Mycoplasma hominis has been implicated in many inflammatory conditions
      of the human urogenital tract in particular amniotic infections that lead to
      fetal and neonatal disease and pre-term labor. The mechanisms responsible are
      poorly defined. METHOD OF STUDY: Biochemical and immunological methods were used
      to extract, purify, and characterize an inflammatory component present in M.
      hominis. RESULTS: We isolated and purified to homogeneity a 40-kDa bioactive
      lipoprotein from M. hominis that was a potent TLR2-dependent, CD14-independent
      activator of the human THP-1 macrophage cell line. Homology searches of the N
      terminal sequence revealed that 22 of the first 23 residues were identical to
      those seen for the phase-variable M. hominis p50 adhesin. The truncated P50t
      lipoprotein importantly retained its adhesive properties for human macrophages.
      CONCLUSION: The unique adhesin/macrophage activator may play a key role in M.
      hominis infections by triggering an inflammatory cytokine cascade.

PMID- 24939000
TI  - GluN2B N-methyl-D-aspartic acid receptor subunit mediates atorvastatin-Induced
      neuroprotection after focal cerebral ischemia.
AB  - Statins are potent cholesterol biosynthesis inhibitors that exert protective
      effects in humans and in experimental models of stroke. The mechanisms involved
      in these protective actions are not completely understood. This study evaluates
      whether atorvastatin (ATV) treatment affects the GluN1 and GluN2B subunits of the
      N-methyl-D-aspartic acid receptor in the somatosensory cerebral cortex at short
      and long periods following ischemia. Sham and ischemic male Wistar rats received
      10 mg/kg of ATV or placebo by gavage every 24 hr for 3 consecutive days. The
      first dose was administered 6 hr after ischemia-reperfusion or the sham
      operation. ATV treatment resulted in faster recovery of neurological scores than
      placebo, prevented the appearance of pyknotic neurons, and restored microtubule
      associated protein 2 and neuronal nuclei staining to control values in the
      somatosensory cerebral cortex and the hippocampus at 72 hr and 15 days
      postischemia. Furthermore, ATV prevented spatial learning and memory deficits
      caused by cerebral ischemia. Cerebral ischemia reduced the number of GluN1/PSD-95
      and GluN2B/PSD-95 colocalization clusters in cortical pyramidal neurons and
      reduced the levels of brain-derived neurotrophic factor (BDNF) in the cerebral
      cortex. These effects of the ischemic insult were prevented by ATV, which also
      induced GluN2B/PSD-95 colocalization in neuronal processes and an association of
      GluN2B with TrkB. The GluN2B pharmacological inhibitor ifenprodil prevented the
      increase in BDNF levels and the motor and cognitive function recovery caused by
      ATV in ischemic rats. These findings indicate that GluN2B is involved in the
      neuroprotective mechanism elicited by ATV to promote motor and cognitive recovery
      after focal cerebral ischemia.

PMID- 24939001
TI  - Amigos and amistades: the role of men's social network ties in shaping HIV
      vulnerability in the Dominican Republic.
AB  - While men's social networks have been identified as a source of influence on
      sexual behaviour, less is known about the different types of friendship ties
      within men's networks. We analysed data from qualitative in-depth interviews with
      36 men in Santo Domingo, Dominican Republic who are current or former sexual
      partners of female sex workers to understand how: (1) men describe trust and
      communication with different types of friendship ties, (2) characteristics of
      trust and communication reflect norms of masculinity, and (3) these friendship
      ties influence HIV-related behaviours. We identified a distinction between
      amistades, social drinking buddies who are not trusted, and amigos, trusted
      friends. The majority of men lacked any amigos and some had neither amigos nor
      amistades. In general, men reflected traditional norms of masculinity and said
      they did not feel they could discuss their relationships or emotional topics with
      other men. Trust and communication dynamics, and how norms of masculinity shape
      those dynamics, should be understood and addressed in the design of HIV
      prevention efforts with men's social networks as they have implications for the
      potential effectiveness of such efforts. 

PMID- 24939002
TI  - Odor identification in frontotemporal lobar degeneration subtypes.
AB  - Odor identification impairment is a feature of several neurodegenerative
      disorders. Although neurodegenerative changes in the frontotemporal lobar
      degeneration (FTLD) subtypes involve areas important for olfactory processing,
      data on olfactory function in these patients are limited. An 18-item, multiple
      choice odor identification test developed at our memory clinic, the Motol
      Hospital smell test, was administered to 9 patients with behavioral variant
      frontotemporal dementia, 13 patients with the language variants, primary
      nonfluent aphasia (n = 7) and semantic dementia (n = 6), and 8 patients with
      progressive supranuclear palsy. Compared to the control group (n = 15), all FTLD
      subgroups showed significant impairment of odor identification (P < .05). The
      differences between the FTLD subgroups were not significant. No correlation
      between odor identification and neuropsychological tests results was found. Our
      data suggest that odor identification impairment is a symptom common to FTLD
      syndromes, and it seems to be based on olfactory structure damage rather than
      cognitive decline.

PMID- 24939003
TI  - Prognosis of short survival in patients with advanced dementia as diagnosed by
      Aminoff suffering syndrome.
AB  - On the first few days after admission to the Geriatric-Internal Medicine
      department, the suffering level of patients with advanced dementia (Mini-Mental
      State Examination 0 of 30) was evaluated according to the Mini-Suffering State
      Examination (MSSE). During hospitalization, 14.8% (27 of 183) of patients with
      advanced dementia were died with a mean survival rate of 19.86 +/- 26.9 days. The
      MSSE scale score of died patients was 7.56 +/- 1.71 during the first few days of
      admission which indicates high suffering levels. The MSSE scale score of survived
      patients with advanced dementia was 3.99 +/- 2.10 which confirms their low level
      of suffering. There was a significant difference (P < .001) between the groups.
      Patients with dementia who died and were diagnosed as having Aminoff suffering
      syndrome during the first few days of admission had a high suffering level and
      short-survival time.

PMID- 24939004
TI  - Religious Affiliation, Religious Service Attendance, and Mortality.
AB  - Very few studies have examined the effects of both religious affiliation and
      religiosity on mortality at the same time, and studies employing multiple
      dimensions of religiosity other than religious attendance are rare. Using the
      newly created General Social Survey-National Death Index data, our report
      contributes to the religion and mortality literature by examining religious
      affiliation and religiosity at the same time. Compared to Mainline Protestants,
      Catholics, Jews, and other religious groups have lower risk of death, but Black
      Protestants, Evangelical Protestants, and even those with no religious
      affiliation are not different from Mainline Protestants. While our study is
      consistent with previous findings that religious attendance leads to a reduction
      in mortality, we did not find other religious measures, such as strength of
      religious affiliation, frequency of praying, belief in an afterlife, and belief
      in God to be associated with mortality. We also find interaction effects between
      religious affiliation and attendance. The lowest mortality of Jews and other
      religious groups is more apparent for those with lower religious attendance.
      Thus, our result may emphasize the need for other research to focus on the
      effects of religious group and religious attendance on mortality at the same
      time. 

PMID- 24939006
TI  - Health system report ranks UK first, US last.

PMID- 24939005
TI  - Understanding visual search patterns of dermatologists assessing pigmented skin
      lesions before and after online training.
AB  - The goal of this investigation was to explore the feasibility of characterizing
      the visual search characteristics of dermatologists evaluating images
      corresponding to single pigmented skin lesions (PSLs) (close-ups and dermoscopy)
      as a venue to improve training programs for dermoscopy. Two Board-certified
      dermatologists and two dermatology residents participated in a phased study. In
      phase I, they viewed a series of 20 PSL cases ranging from benign nevi to
      melanoma. The close-up and dermoscopy images of the PSL were evaluated
      sequentially and rated individually as benign or malignant, while eye position
      was recorded. Subsequently, the participating subjects completed an online
      dermoscopy training module that included a pre- and post-test assessing their
      dermoscopy skills (phase 2). Three months later, the subjects repeated their
      assessment on the 20 PSLs presented during phase I of the study. Significant
      differences in viewing time and eye-position parameters were observed as a
      function of level of expertise. Dermatologists overall have more efficient search
      than residents generating fewer fixations with shorter dwells. Fixations and
      dwells associated with decisions changing from benign to malignant or vice versa
      from photo to dermatoscopic viewing were longer than any other decision,
      indicating increased visual processing for those decisions. These differences in
      visual search may have implications for developing tools to teach dermatologists
      and residents about how to better utilize dermoscopy in clinical practice. 

PMID- 24939007
TI  - [Gender-specific differences in comorbidities of rheumatoid arthritis].
AB  - BACKGROUND: Comorbidities play an important role in the course and therapy of
      rheumatoid arthritis (RA). Sex-specific aspects are observed with regard to
      prevalence and manifestation of RA-related comorbidities. AIM: A summary of
      current insights into sex and gender-related aspects of frequent comorbidities in
      RA is given. MATERIAL AND METHODS: National data were analyzed and literature
      findings from meta-analyses, observational studies and reviews with regard to
      gender and RA-associated comorbidities are presented. RESULTS: There are gender
      specific differences in the prevalence of comorbidities of RA. Depression,
      fibromyalgia and hypothyroidism are more frequent in women than in men, whereas
      cardiovascular diseases and diabetes are more common in men. Osteoarthritis and
      osteoporosis are frequent in both sexes. CONCLUSION: Sex and gender-specific
      aspects should be taken into consideration in the diagnostics and treatment of RA
      related comorbidities.

PMID- 24939008
TI  - CRKL amplification is rare as a mechanism for acquired resistance to kinase
      inhibitors in lung cancers with epidermal growth factor receptor mutation.
AB  - OBJECTIVES: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors
      (TKIs) often provide dramatic responses in lung cancer patients with somatic EGFR
      mutation. However, acquired resistance to the drugs usually emerges within a few
      years. EGFR T790M secondary mutation, MET gene amplification, and transformation
      to small cell lung cancer are well-validated mechanisms that underlie acquisition
      of resistance to EGFR-TKIs. In addition, many molecular aberrations have been
      reported as candidates for mechanisms of acquired resistance to EGFR-TKIs.
      Amplification of the CRKL gene was reportedly observed in 1 of 11 lung cancer
      patients with EGFR mutations who acquired resistance to EGFR-TKI. This study is
      the first report, to our knowledge, that validated the role of CRKL gene
      amplification as a mechanism for acquisition of resistance to EGFR-TKIs.
      MATERIALS AND METHODS: We analyzed CRKL gene copy numbers, using a quantitative
      real-time PCR method, in 2 in vitro acquired-resistance cell-line models: 11
      clinical samples from patients who developed acquired resistance to EGFR-TKIs,
      and 39 tumor specimens obtained from 7 autopsy patients whose cancers acquired
      resistance to EGFR-TKIs. Mutational status of EGFR codon 790 and copy numbers for
      the MET gene were also determined. RESULTS AND CONCLUSION: In analysis for in
      vitro models, CRKL gene copy numbers were identical between EGFR-TKI-sensitive
      parental cells and their acquired resistant descendant cells. In addition, we
      found no clinical tumor specimens with acquired EGFR-TKI resistance to harbor
      amplified CRKL genes. These results indicate that CRKL gene amplification is rare
      in acquisition of resistance to EGFR-TKIs in lung cancer patients with EGFR
      mutations.

PMID- 24939010
TI  - A safe and reliable technique in the management of pseudocyst pinna.

PMID- 24939009
TI  - IgG, IgM and IgA antibodies against the novel polyprotein in active tuberculosis.
AB  - BACKGROUND: The present study was aimed to evaluate whether IgG, IgM and IgA
      antibodies levels detected against a novel Mycobacterium tuberculosis polyprotein
      38 F-64 F (with 38 F being the abbreviation for 38kD-ESAT6-CFP10 and 64 F for
      Mtb8.4-MPT64-TB16.3-Mtb8) are suitable for diagnosing active tuberculosis, and
      for monitoring the efficacy of chemotherapy on TB patients. METHODS: In this
      study, a total of 371 active TB patients without treatment were selected and
      categorized into S+/C+group (n=143), S-/C+group (n=106) or S-/C- group (n=122). A
      series of serum samples were collected from 82 active TB patients who had
      undergone anti-TB chemotherapy for 0-6 months at one month interval. Humoral
      responses (IgG, IgM and IgA) were determined for the novel Mycobacterium
      tuberculosis polyprotein using indirect ELISA methods in all of serum samples.
      RESULTS: For S+/C+, S-/C+and S-/C- active tuberculosis patients before anti-TB
      chemotherapy, the sensitivities of tests based on IgG were 65.7%, 46.2% and 52.5%
      respectively; the sensitivities based on IgM were 21.7%, 24.5% and 18.9%; and the
      sensitivities based on IgA were 25.2%, 17.9% and 23.8%. By combination of three
      isotypes, for all active tuberculosis patients, the test sensitivity increased to
      70.4% with the specificity being 91.5%. After anti-TB chemotherapy, there were no
      significant differences between groups with different courses of anti-TB
      chemotherapy. CONCLUSIONS: The novel Mycobacterium tuberculosis polyprotein 38 F
      64 F represents potential antigen suitable for measuring IgG, IgM and IgA
      antibodies. However, the serodiagnostic test based on the 38 F-64 F polyprotein
      appears unsuitable for monitoring the efficacy of chemotherapy.

PMID- 24939011
TI  - Conversion of (eta(5)-C2B9H10R)TaX3 (X = Me, NMe2) to (eta(6)-C2B9H10R)TaX' (X' =
      NMe2, azaallyl) in the absence of a reducing agent: synthesis and structure of
      tantallacarboranes incorporating an arachno-eta(6)-C2B9(4-) ligand.
AB  - Heating a benzene solution of [eta(5)-(Me2NCH2CH2)C2B9H10] Ta(NMe2)3 (1) in the
      presence of pyridine gave an unprecedented complex [eta(1):eta(6)
      (Me2NCH2CH2)C2B9H10]Ta (NMe2)(NC5H5) (2). On the other hand, reaction of (eta(5)
      C2B9H11)TaMe3 with adamantly isonitrile (AdNC) in dimethoxyethane (DME) at room
      temperature afforded another unexpected complex (eta(6)-C2B9H11)Ta[eta(3)-C,C,N
      CH2C(CH3)NAd](DME) (4). These results show that pyridine and DME are essential
      for the formation of 2 and 4, respectively. It is suggested that the nido-eta(5)
      C2B9H10R(2-) ligand in tantallacarboranes takes up two electrons released by
      reductive elimination to form an arachno-eta(6)-C2B9H10R(4-) fragment via the
      cage C-C bond cleavage.

PMID- 24939012
TI  - Therapeutic effect of anti-C-X-C motif chemokine 10 (CXCL10) antibody on C
      protein-induced myositis mouse.
AB  - INTRODUCTION: C-X-C motif chemokine 10 (CXCL10) is a chemokine that plays a
      critical role in the infiltration of T cells in autoimmune diseases and is
      reported to be expressed in muscle tissue of polymyositis. To determine the
      therapeutic efficacy of CXCL10 blockade, we investigated the role of CXCL10 and
      the effect of anti-CXCL10 antibody treatment in C protein-induced myositis (CIM),
      an animal model of polymyositis. METHODS: CIM was induced with human skeletal
      muscle C protein fragment in female C57BL/6 mice. Immunohistochemistry of CXCL10
      and C-X-C motif chemokine receptor 3 (CXCR3) and measurement of serum CXCL10 were
      performed. Cell surface markers and interferon-gamma (IFN-gamma) and tumor
      necrosis factor-alpha (TNF-alpha) in CIM lymph node cells was investigated by
      flow cytometry. Mice with CIM were treated with anti-CXCL10 antibody or control
      antibody (anti-RVG1) and the inflammation in muscle tissue was assessed. RESULTS:
      Immunohistochemistry showed increased expression of CXCL10 and CXCR3 in the
      inflammatory lesions of muscle in CIM. Especially, CD8+ T cells invading myofiber
      expressed CXCR3. Serum level of CXCL10 was increased in CIM compared to the level
      in normal mice (normal mouse, 14.3 +/- 5.3 pg/ml vs. CIM, 368.5 +/- 135.6 pg/ml,
      P < 0.001). CXCR3 positivity in CD8+ T cells was increased compared to that of
      CD4+ T cells in the lymph node cells of CIM (CXCR3+ among CD8+ T cell, 65.9 +/-
      2.1% vs. CXCR3+ among CD4+ T cell, 23.5 +/- 4.7%, P <0.001). Moreover, IFN-gamma+
      cells were increased among CXCR3+CD8+ T cells compared to CXCR3-CD8+ T cells
      (CXCR3+CD8+ T cell, 28.0 +/- 4.2% vs. CXCR3-CD8+ T cell, 9.5 +/- 1.5%, P =
      0.016). Migration of lymph node cells was increased in response to CXCL10
      (chemotactic index was 1.91 +/- 0.45). CIM mice treated with anti-CXCL10 antibody
      showed a lower inflammation score in muscles than those with anti-RVG1 (median,
      anti-CXCL10 treatment group, 0.625 vs. anti-RVG1 treatment group, 1.25, P =
      0.007). CONCLUSIONS: CXCL10/CXCR3 expression was increased in the inflammation of
      CIM model and its blockade suppressed inflammation in muscle.

PMID- 24939013
TI  - An exploratory review of HIV prevention mass media campaigns targeting men who
      have sex with men.
AB  - BACKGROUND: Men who have sex with men (MSM) are at increased risk of HIV
      infection in both high- and low-income settings. Mass media campaigns have been
      used as a means of communicating HIV health promotion messages to large audiences
      of MSM. There is no consensus on which designs are most appropriate to evaluate
      the process and outcomes of such interventions. METHODS: An exploratory review
      was conducted to assess research examining awareness, acceptability, effects on
      HIV testing, disclosure and sexual risk, and cost-effectiveness of HIV mass media
      campaigns targeting MSM. We searched for quantitative and qualitative studies
      published between 1990 and May 2011 via the Cochrane Central Register of
      Controlled Trials, MEDLINE, EMBASE, Psych Info, ISI Web of Science, OpenGrey and
      COPAC, and contacting experts. No exclusions were made on the basis of study
      design or methods because our primary aim was to map evidence. We appraised study
      quality and present a narrative synthesis of findings. RESULTS: Sixteen reports
      from 12 studies were included. All were from high-income countries and most
      examined multi-media interventions. Half of the studies were single cross
      sectional surveys. Three repeat cross-sectional studies collected data pre and
      post the campaign launch. The remaining three studies monitored routine data.
      Three studies included a nested qualitative component. Campaign coverage was the
      most commonly reported outcome (9 studies). Imagery, tone of language, content
      and relevance were identified in the qualitative research as factors influencing
      campaign acceptability. HIV testing rates (or intention to test) were reported by
      five studies. Two studies reported that testing rates were higher among men who
      had seen the campaigns compared to men who had not, but this may reflect
      confounding. Findings were less consistent regarding reductions in sexual risk
      behaviours (4 studies). None of the studies examined cost-effectiveness.
      CONCLUSIONS: Campaigns aim to provide MSM with information to help prevent
      transmission of HIV and to address increasing motivation and changing norms
      towards precautionary behaviours. However, the limitations of mass media in
      imparting skills in effecting behaviour change should be recognised, and
      campaigns supplemented by additional components may be better-suited to achieving
      these goals.

PMID- 24939015
TI  - From an alpha-functionalized silicon-stereogenic N,O-silane to a monomeric and
      tetracoordinate tBuLi adduct with lithium-centered chirality.
AB  - Donor-functionalized silanes with stereogenic silicon centers are extremely rare.
      A convenient stereocontrolled route to a nitrogen-oxygen-functionalized silicon
      chiral compound with an additional aminomethyl function is presented. This silane
      was directly achieved in stereochemically pure form by a simple nucleophilic
      substitution reaction. Owing to the unique asymmetry of this silane and the
      presence of three donor functions, the first monomeric butyllithium compound with
      lithium-centered chirality could be isolated; the configuration was assigned by X
      ray crystallography. This [silane? tBuLi] complex undergoes an unexpected
      deprotonation/stereospecific substitution sequence in toluene, leading to the
      development of a convenient one-pot synthesis of a functionalized silicon-chiral
      benzylsilane, which proceeds with inversion of configuration and complete
      preservation of the stereochemical integrity at silicon. 

PMID- 24939014
TI  - Adolescent predictors of young adult cyberbullying perpetration and victimization
      among Australian youth.
AB  - PURPOSE: The purpose of the current article was to examine the adolescent risk
      and protective factors (at the individual, peer group, and family level) for
      young adult cyberbullying perpetration and victimization. METHODS: Data from 2006
      (Grade 9) to 2010 (young adulthood) were analyzed from a community sample of 927
      Victorian students originally recruited as a statewide representative sample in
      Grade 5 (age, 10-11 years) in 2002 and followed-up to age 18-19 years in 2010 (N
      = 809). Participants completed a self-report survey on adolescent risk and
      protective factors and traditional and cyberbullying perpetration and
      victimization and young adult cyberbullying perpetration and victimization.
      RESULTS: As young adults, 5.1% self-reported cyberbullying perpetration only,
      5.0% reported cyberbullying victimization only, and 9.5% reported both
      cyberbullying perpetration and victimization. In fully adjusted logistic
      regression analyses, the adolescent predictors of cyberbullying perpetration only
      were traditional bullying perpetration, traditional bullying perpetration and
      victimization, and poor family management. For young adulthood cyberbullying
      victimization only, the adolescent predictor was emotion control. The adolescent
      predictors for young adult cyberbullying perpetration and victimization were
      traditional bullying perpetration and cyberbullying perpetration and
      victimization. CONCLUSIONS: Based on the results of this study, possible targets
      for prevention and early intervention are reducing adolescent involvement in
      (traditional or cyber) bullying through the development of social skills and
      conflict resolution skills. In addition, another important prevention target is
      to support families with adolescents to ensure that they set clear rules and
      monitor adolescents' behavior. Universal programs that assist adolescents to
      develop skills in emotion control are warranted.

PMID- 24939017
TI  - Editorial.

PMID- 24939016
TI  - Liver transcriptome analysis of Atlantic cod (Gadus morhua) exposed to PCB 153
      indicates effects on cell cycle regulation and lipid metabolism.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent organic pollutants
      (POPs) with harmful effects in animals and humans. Although PCB 153 is one of the
      most abundant among PCBs detected in animal tissues, its mechanism of toxicity is
      not well understood. Only few studies have been conducted to explore genes and
      pathways affected by PCB 153 by using high throughput transcriptomics approaches.
      To obtain better insights into toxicity mechanisms, we treated juvenile Atlantic
      cod (Gadus morhua) with PCB 153 (0.5, 2 and 8 mg/kg body weight) for 2 weeks and
      performed gene expression analysis in the liver using oligonucleotide arrays.
      RESULTS: Whole-genome gene expression analysis detected about 160 differentially
      regulated genes. Functional enrichment, interactome, network and gene set
      enrichment analysis of the differentially regulated genes suggested that pathways
      associated with cell cycle, lipid metabolism, immune response, apoptosis and
      stress response were among the top significantly enriched. Particularly, genes
      coding for proteins in DNA replication/cell cycle pathways and enzymes of lipid
      biosynthesis were up-regulated suggesting increased cell proliferation and
      lipogenesis, respectively. CONCLUSIONS: PCB 153 appears to activate cell
      proliferation and lipogenic genes in cod liver. Transcriptional up-regulation of
      marker genes for lipid biosynthesis resembles lipogenic effects previously
      reported for persistent organic pollutants (POPs) and other environmental
      chemicals. Our results provide new insights into mechanisms of PCB 153 induced
      toxicity.

PMID- 24939018
TI  - The 2014 American Heart Association/American College of Cardiology guideline for
      the management of patients with valvular heart disease: a changing landscape.

PMID- 24939019
TI  - Hybrid repair is an effective strategy for repair of Kommerell diverticulum in
      the modern era.

PMID- 24939020
TI  - Reply to the editor.

PMID- 24939021
TI  - Ross operation or aortic valve repair in neonates and infants?

PMID- 24939022
TI  - Reply to the editor.

PMID- 24939023
TI  - Sutureless valves in aortic stenosis.

PMID- 24939024
TI  - Sutureless versus transcatheter aortic valve implantation: an unresolved dilemma.

PMID- 24939025
TI  - Reply to the editor.

PMID- 24939026
TI  - Modifiable risk factors for acute kidney injury after coronary artery bypass
      grafting.

PMID- 24939027
TI  - Reply to the editor.

PMID- 24939028
TI  - Reply to the editor.

PMID- 24939029
TI  - Is earlier aortic valve surgery in repair candidates justified?

PMID- 24939030
TI  - Cox maze III procedure: the best alternative in surgery for atrial fibrillation.

PMID- 24939031
TI  - Autophagy and the human heart.

PMID- 24939032
TI  - Who should decide margin length in pulmonary excision of lung cancer?

PMID- 24939034
TI  - Closing the clinical-radiological paradox using the visual pathway in multiple
      sclerosis.

PMID- 24939035
TI  - Occurrence of phosphorylated castasterone in Arabidopsis thaliana and
      Lycopersicum esculentum.
AB  - An in vitro enzyme assay using radioisotope-labeled (3) H-castasterone ((3) H-CS)
      or (32) P-ATP showed that CS can be phosphorylated by ATP in Arabidopsis and
      tomato plants. Gas chromatography-mass spectrometry (GC-MS) analysis using non
      isotope-labeled CS and ATP revealed that the phosphorylation of CS occurs at the
      side chain, most likely at the C-23 hydroxyl. The polar fractions than free
      brassinosteroids (BRs) obtained from extracts of Arabidopsis and tomato showed
      almost no BRs activity in a rice lamina inclination bioassay. However, the
      fractions showed increased bioactivity after treatment with wheat germ acidic
      phosphatase (WGAP). Additionally, CS was identified from the hydrolysate by WGAP
      using GC-MS analysis in both plants. In contrast, the polar fractions obtained
      from BR-deficient mutants, Arabidopsis cyp85a2 and tomato d(x) , did not show an
      increase in biological activity with WGAP treatment, and no free BRs, including
      CS, were detected in the hydrolysate. This suggests that CS phosphate is a
      naturally occurring biologically inactive conjugate that is generated when CS is
      normally synthesized in Arabidopsis and tomato plants. Taken together, these
      results suggest that phosphorylation of CS is an important conjugation process
      for the maintenance of the homeostatic level of an active BR and thus the
      regulation of the growth and development of plants. 

PMID- 24939036
TI  - High energy product developed from cobalt nanowires.
AB  - Cobalt nanowires with high aspect ratio have been synthesized via a solvothermal
      chemical process. Based on the shape anisotropy and orientation of the nanowire
      assemblies, a record high room-temperature coercivity of 10.6 kOe has been
      measured in Co nanowires with a diameter of about 15 nm and a mean length of 200
      nm. As a result, energy product of the wires reaches 44 MGOe. It is discovered
      that the morphology uniformity of the nanowires is the key to achieving the high
      coercivity and high energy density. Nanowires of this type are ideal building
      blocks for future bonded, consolidated and thin film magnets with high energy
      density and high thermal stability.

PMID- 24939033
TI  - 2014 AHA/ACC guideline for the management of patients with valvular heart
      disease: a report of the American College of Cardiology/American Heart
      Association Task Force on Practice Guidelines.

PMID- 24939037
TI  - Interplay between trigger factor and other protein biogenesis factors on the
      ribosome.
AB  - Nascent proteins emerging from translating ribosomes in bacteria are screened by
      a number of ribosome-associated protein biogenesis factors, among them the
      chaperone trigger factor (TF), the signal recognition particle (SRP) that targets
      ribosomes synthesizing membrane proteins to the membrane and the modifying
      enzymes, peptide deformylase (PDF) and methionine aminopeptidase (MAP). Here, we
      examine the interplay between these factors both kinetically and at equilibrium.
      TF rapidly scans the ribosomes until it is stabilized on ribosomes presenting TF
      specific nascent chains. SRP binding to those complexes is strongly impaired.
      Thus, TF in effect prevents SRP binding to the majority of ribosomes, except
      those presenting SRP-specific signal sequences, explaining how the small amount
      of SRP in the cell can be effective in membrane targeting. PDF and MAP do not
      interfere with TF or SRP binding to translating ribosomes, indicating that
      nascent-chain processing can take place before or in parallel with TF or SRP
      binding. 

PMID- 24939038
TI  - Bioactive components of Glycyrrhiza uralensis mediate drug functions and
      properties through regulation of CYP450 enzymes.
AB  - Glycyrrhiza uralensis (G. uralensis) is a common medicinal plant that has mainly
      been used to modulate the pharmaceutical activity of herbal medicines. Although
      G. uralensis has been shown to affect the expression and activity of the key
      metabolic enzyme cytochrome P450 (CYP450), the detailed mechanism of this process
      has yet to be elucidated. The present study aimed to elucidate the effects of
      bioactive components of G. uralensis on different isoforms of CYP450 and
      determine the ability of these components to modulate drug properties. In the
      present study, mRNA levels of CYP1A2, CYP2D6, CYP2E1, and CYP3A4 were
      investigated by quantitative polymerase chain reaction (qPCR) in HepG2 cells
      following treatment with the major bioactive compounds of G. uralensis. The
      activity of CYP450 enzymes was investigated in human liver microsomes using the
      cocktail probe drug method, and the metabolites of specific probes were detected
      by UPLC-MS/MS. The effects of G. uralensis on CYP450 were assessed using
      bioinformatics network analysis. Several compounds from G. uralensis had various
      effects on the expression and activity of multiple CYP450 isoforms. The majority
      of the compounds analysed the inhibited expression of CYP2D6 and CYP3A4. Several
      CYP isoforms were differentially modulated depending on the specific compound and
      dose tested. In conclusion, the present study suggested that G. uralensis
      influenced the expression and activity of CYP450 enzymes. Therefore, caution
      should be taken when G. uralensis is co-administered with drugs that are known to
      be metabolized by CYP450. This study contributed to the knowledge of the
      mechanisms by which this medicinal plant, commonly known as licorice, modulates
      drug efficacy.

PMID- 24939040
TI  - Epigenetic chromatin modifications in barley after mutagenic treatment.
AB  - In addition to their normal developmental processes, plants have evolved complex
      genetic and epigenetic regulatory mechanisms to cope with various environmental
      stresses. It has been shown that both DNA methylation and histone modifications
      are involved in DNA damage response to various types of stresses. In this study,
      we focused on the involvement of two mutagenic agents, chemical (maleic acid
      hydrazide; MH) and physical (gamma rays), on the global epigenetic modifications
      of chromatin in barley. Our results indicate that both mutagens strongly
      influence the level of histone methylation and acetylation. Moreover, we found
      that gamma irradiation, in contrast to MH, has a more robust influence on the DNA
      methylation level. This is the first study that brings together mutagenic
      treatment along with its impact at the level of epigenetic modifications examined
      using the immunohistochemical method. 

PMID- 24939039
TI  - Predictors of antiemetic alteration in pediatric acute myeloid leukemia.
AB  - BACKGROUND: Better knowledge of patient and cancer treatment factors associated
      with nausea/vomiting (NV) in pediatric oncology patients could enhance
      prophylaxis. We aimed to describe such factors in children receiving treatment
      for acute myeloid leukemia (AML). METHODS: Retrospective longitudinal cohort
      study of 1,668 hospitalized children undergoing treatment for AML from the
      Pediatric Health Information System database (39 hospitals, 1999-2010).
      Antiemetic alteration, which included switch (a change in prescribed 5-HT3
      receptor antagonists) and rescue (receipt of an adjunct antiemetic), were first
      validated and then used as surrogates of problematic NV. Logistic and negative
      binomial regression modeling were used to test whether patient characteristics
      were associated with problematic NV. RESULTS: Increasing age is associated with
      greater odds of experiencing antiemetic switch and higher relative rate of
      antiemetic rescue. Within a treatment cycle, each consecutive inpatient
      chemotherapy day decreased the likelihood of requiring antiemetic alteration.
      Each consecutive inpatient-day post-chemotherapy was associated with decreased
      need for switch, but increased need for rescue. Subsequent cycles of AML therapy
      were associated with lower odds of antiemetic switch on both chemotherapy and non
      chemotherapy days, a lower rate of antiemetic rescue on chemotherapy days, and an
      increased rate of rescue on non-chemotherapy days. CONCLUSION: In pediatric
      patients with AML, increasing age is strongly associated with greater antiemetic
      alteration. Antiemetic alteration occurs early in treatment overall, and early
      within each admission. While additional cycles of therapy are associated with
      less alteration overall, there is persistent rescue in the days after
      chemotherapy, suggesting additional etiologies of NV in pediatric cancer
      patients.

PMID- 24939041
TI  - Phase-contrast X-ray CT imaging of esophagus and esophageal carcinoma.
AB  - The electron density resolution is 1000 times higher for synchrotron-radiation
      phase-contrast CT imaging than conventional X-ray absorption imaging in light
      elements, with which high-resolution X-ray imaging of biological soft tissue can
      be achieved. In the present study, we used phase-contrast X-ray CT to investigate
      human resected esophagus and esophageal carcinoma specimens. This technology
      revealed the three-layer structure of the esophageal wall-- mucous, submucosa and
      muscular layers. The mucous and muscular layers were clearly separated by a loose
      submucosa layer with a honeycomb appearance. The surface of the mucous layer was
      smooth. In esophageal carcinoma, because of tumor tissue infiltration, the
      submucosa layer was absent, which indicated destruction of the submucosa. The
      boundary between normal tissue and tumor was comparatively fuzzy, the three-layer
      structure of the esophageal wall was indistinct. The surface of the mucous layer
      was rugose. The technology might be helpful in tumor staging of esophageal
      carcinoma. 

PMID- 24939042
TI  - High-performing red-light-emitting pyrotechnic illuminants through the use of
      perchlorate-free materials.
AB  - The development of perchlorate-free M662 40 mm illuminating pyrotechnic
      compositions is described. On the bases of cost, performance, and sensitivity,
      potassium periodate was determined to be most effective potassium perchlorate
      replacement in the compositions tested. The optimal periodate-based composition
      exceeded the performance of the perchlorate-containing control, exhibited low
      sensitivity values to impact, friction, and electrostatic discharge, and had high
      thermal onset temperatures. 

PMID- 24939044
TI  - Deep vein thrombosis.

PMID- 24939043
TI  - Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma
      volume in patients with type 2 diabetes mellitus.
AB  - AIM: To evaluate the effects of canagliflozin on plasma volume, urinary glucose
      excretion (UGE), fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and
      additional measures of fluid/electrolyte balance in patients with type 2 diabetes
      on background therapy with metformin and angiotensin-converting enzyme inhibitors
      or angiotensin receptor blockers. METHODS: Patients (N = 36) were randomized
      (1:1) to receive canagliflozin 300 mg or placebo for 12 weeks. Pharmacodynamic
      parameters were assessed at baseline and at weeks 1 and 12. RESULTS: Increased 24
      h UGE was seen in the canagliflozin group compared with a reduction in the
      placebo group at both week 1 (91.8 vs. -2.4 g) and week 12 (82.6 vs. -0.4 g).
      Canagliflozin also reduced both FPG and HbA1c. Reductions in body weight and
      blood pressure were observed at weeks 1 and 12. Canagliflozin decreased plasma
      volume compared with an increase with placebo at week 1 (-5.4 vs. 4.3%; p =
      0.02), but this was largely attenuated at week 12 (4.6 vs. 5.8%; p = 0.76). A
      modest numerical increase in urine volume was observed with canagliflozin at week
      1 that was attenuated at week 12; other measures of volume status (i.e. blood
      urea nitrogen, serum creatinine and haematocrit) remained modestly increased with
      canagliflozin at week 12. CONCLUSION: Canagliflozin provided sustained effects on
      UGE and FPG over 12 weeks and a transient reduction in plasma volume that was
      largely attenuated by week 12.

PMID- 24939047
TI  - Transition from the spouse dementia caregiver role: A change for the better?
AB  - One in 15 Australians over 65 experience dementia, and are commonly supported by
      spouses. Evidence demonstrates declining wellbeing for these caregivers as their
      role continues. There are indications of improvement once caregivers transition
      out of the role (recovery) but alternate suggestions that caregiving stress may
      be too damaging to be appeased (wear and tear). It seems plausible that reason
      for transition (care recipient's move into residential care or death) will affect
      caregivers' outcomes. A synthetic cohort method compared caregivers' stress and
      wellbeing prior to, and one and two years post-transition. There was evidence of
      wear and tear for physical wellbeing but recovery for psychological wellbeing
      over time; with little difference based on reason for transition. Caregiver
      outcomes seem to be a function of the action rather than the reason for
      transition, but factors such as age must be considered when designing methods to
      support post-transition wellbeing. 

PMID- 24939046
TI  - The bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1) provides long
      term survival in a murine glioma model.
AB  - BACKGROUND: Glioblastomas are largely unresponsive to all available treatments
      and there is therefore an urgent need for novel therapeutics. Here we have probed
      the antineoplastic effects of a bacterial protein toxin, the cytotoxic
      necrotizing factor 1 (CNF1), in the syngenic GL261 glioma cell model. CNF1
      produces a long-lasting activation of Rho GTPases, with consequent blockade of
      cytodieresis in proliferating cells and promotion of neuron health and
      plasticity. METHODS: We have tested the antiproliferative effects of CNF1 on
      GL261 cells and human glioma cells obtained from surgical specimens. For the in
      vivo experiments, we injected GL261 cells into the adult mouse visual cortex, and
      five days later we administered either a single intracerebral dose of CNF1 or
      vehicle. To compare CNF1 with a canonical antitumoral drug, we infused
      temozolomide (TMZ) via minipumps for 1 week in an additional animal group.
      RESULTS: In culture, CNF1 was very effective in blocking proliferation of GL261
      cells, leading them to multinucleation, senescence and death within 15 days. CNF1
      had a similar cytotoxic effect in primary human glioma cells. CNF1 also inhibited
      motility of GL261 cells in a scratch-wound migration assay. Low dose (2 nM) CNF1
      and continuous TMZ infusion significantly prolonged animal survival (median
      survival 35 days vs. 28 days in vehicle controls). Remarkably, increasing CNF1
      concentration to 80 nM resulted in a dramatic enhancement of survival with no
      obvious toxicity. Indeed, 57% of the CNF1-treated animals survived up to 60 days
      following GL261 glioma cell transplant. CONCLUSIONS: The activation of Rho
      GTPases by CNF1 represents a novel potential therapeutic strategy for the
      treatment of central nervous system tumors.

PMID- 24939048
TI  - Trends in referred patient profiles in a memory clinic over 20 years.
AB  - The increasing numbers of people with dementia in the UK, as well as the
      associated costs have led to an effort to improve dementia services for the
      benefit of patients, caregivers and the taxpayer. These efforts have frequently
      emphasised the importance of early diagnosis in dementia care. We sought to test
      the hypotheses that the mean cognitive score of new referrals to a secondary care
      memory assessment service increased while mean age decreased over a period of 20
      years. We retrospectively analysed the data of 1476 patients. The passage of time
      was associated with a significant increase in mean cognitive scores, while there
      was no association between time and age after controlling for other factors. We
      suggest that memory services need to be designed to meet the needs of less
      cognitively impaired patients. In practice this means that using simple screening
      tests is not sufficient in this group of patients. 

PMID- 24939050
TI  - Chronic pelvic ischemia: etiology, pathogenesis, clinical presentation and
      management.
AB  - Overactive Bladder (OAB) and Bladder Pain Syndrome (BPS) although common, are
      vaguely defined and difficult to diagnose and manage etiologies of storage--type
      lower urinary tract symptoms (LUTS). The lack of optimal management options is a
      direct consequence of deficient understanding of the pathophysiologic mechanisms
      underlying these conditions. These conditions are especially prevalent in
      females, and cumulative contemporary epidemiological, clinical and laboratory
      evidence implicates ischemia as one of the key players in the pathophysiologic
      foundation of both these disorders. Taken together they make up 'the' diagnostic
      as well as therapeutic black--hole in urologic practice. Much akin to chronic
      ischemic heart disease, chronic ischemia--reperfusion has been shown to cause
      degenerative changes at cellular and sub--cellular level in the bladder mucosa,
      smooth muscle fibers, and vesical neural and microvascular structures leading to
      a hypersensitive, hyperactive bladder initially, which with time invariably
      progresses into a failed, fibrotic and pressurized bladder. Diagnosis and
      management of these diseases are currently symptom focused and remains a source
      of much frustration. Consideration of role of ischemia connotates hope and could
      lead to a paradigm shift in the management of these patients with a completely
      new therapeutic armamentarium attacking the pathology itself.

PMID- 24939049
TI  - Efficacy of drugs with different mechanisms of action in relieving spontaneous
      pain at rest and during movement in a rat model of osteoarthritis.
AB  - Patients with osteoarthritis (OA) suffer from joint pain aggravated by movement,
      which affect their quality of life. In the present study, a weight bearing
      paradigm for pain at rest and a gait paradigm for pain during movement were
      tested in rats with unilateral knee arthritis induced by an intra-articular
      injection of sodium monoiodoacetate (MIA). At week 3 after MIA (1mg/knee)
      injection, animals developed pain-associated, right-left imbalances of weight
      distribution (weight bearing) or foot print parameters (gait). Diclofenac, at
      doses up to 30 mg/kg orally (p.o.), did not have a significant effect on either
      paradigm. Morphine rectified the weight bearing and gait imbalances at 1 and
      3mg/kg subcutaneously, respectively. The weak opioid and serotonin/norepinephrine
      reuptake inhibitor (SNRI) tramadol also significantly corrected the indices at
      10mg/kg (weight bearing) and 100mg/kg p.o. (gait). The SNRI duloxetine at 30
      mg/kg p.o. corrected the weight bearing imbalance but not gait imbalance. We
      assessed the effect of different drugs on pain-induced disturbances in weight
      distribution and gait in MIA-induced arthritic rats. Analgesic drugs, each with
      different mechanisms of action, were less effective in rectifying the imbalance
      in gait than that in weight distribution. The assessment of the effect of
      analgesics on not only rest pain but pain during movement is valuable for the
      comprehensive examination of their therapeutic efficacies in OA.

PMID- 24939053
TI  - Genomic approaches for the discovery of genes mutated in inherited retinal
      degeneration.
AB  - In view of their high degree of genetic heterogeneity, inherited retinal diseases
      (IRDs) pose a significant challenge for identifying novel genetic causes. Thus
      far, more than 200 genes have been found to be mutated in IRDs, which together
      contain causal variants in >80% of the cases. Accurate genetic diagnostics is
      particularly important for isolated cases, in which X-linked and de novo
      autosomal dominant variants are not uncommon. In addition, new gene- or mutation
      specific therapies are emerging, underlining the importance of identifying
      causative mutations in each individual. Sanger sequencing of selected genes
      followed by cost-effective targeted next-generation sequencing (NGS) can identify
      defects in known IRD-associated genes in the majority of the cases. Exome NGS in
      combination with genetic linkage or homozygosity mapping studies can aid the
      identification of the remaining causal genes. As these are thought to be mutated
      in <1% of the cases, validation through functional modeling in, for example,
      zebrafish and/or replication through the genotyping of large patient cohorts is
      required. In the near future, whole genome NGS in combination with transcriptome
      NGS may reveal mutations that are currently hidden in the noncoding regions of
      the human genome. 

PMID- 24939056
TI  - Computed tomography angiography in the diagnosis of brain death: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Physiological instability and confounding factors may interfere with
      the clinical diagnosis of brain death. Computed tomography angiography (CTA) has
      been suggested as a potential ancillary test for confirmation of brain death, but
      its diagnostic accuracy remains unclear. METHODS: We searched MEDLINE, EMBASE,
      and CENTRAL for studies comparing CTA with other accepted methods of diagnosing
      brain death (clinical or radiographic). Summary estimates of diagnostic accuracy
      were computed using random effects models. Subgroup analyses and meta-regression
      were performed to assess associations between CTA sensitivity and study or
      patient characteristics. RESULTS: Twelve studies, involving 541 patients, were
      included. If the CTA criterion for brain death was complete lack of opacification
      of intracranial vessels, then the pooled sensitivity was 62 % (50-74 %) for
      venous phase and 84 % (75-94 %) for arterial phase imaging. The sensitivity of
      CTA was higher when the criterion for brain death involved absence of
      opacification of internal cerebral veins, either alone (99 %, 97-100 %) or in
      combination with lack of flow to the distal middle cerebral artery branches (85
      %, 77-93 %). CTA sensitivity was not influenced by different reference standards
      (clinical vs. radiographic) or predominant diagnostic category (stroke vs. brain
      trauma). Specificity of CTA could not be adequately determined from the existing
      data. CONCLUSION: Many patients who progress to brain death by accepted clinical
      or radiographic criteria have persistent opacification of proximal intracranial
      vessels when CTA is performed. The specificity of CTA in the diagnosis of brain
      death has not been adequately assessed. Routine use of CTA as an ancillary test
      in the diagnosis of brain death is therefore not recommended until diagnostic
      criteria have undergone further refinement and prospective validation. Absence of
      opacification of the internal cerebral veins appears to be the most promising
      angiographic criterion.

PMID- 24939055
TI  - Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with
      PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models.
AB  - PURPOSE: Although the EGF receptor tyrosine kinase inhibitors (EGFR-TKI)
      gefitinib have shown dramatic effects against EGFR mutant lung cancer, patients
      become resistant by various mechanisms, including gatekeeper EGFR-T790M mutation,
      MET amplification, and KRAS mutation, thereafter relapsing. AZD6244 is a potent,
      selective, and orally available MEK1/2 inhibitor. In this study, we evaluated the
      therapeutic efficacy of AZD6244 alone or with BEZ235, an orally available potent
      inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of
      rapamycin (mTOR), in gefitinib-resistant non-small cell lung carcinoma (NSCLC)
      models. EXPERIMENTAL DESIGN: NCI-H1975 with EGFR-T790M mutation, NCI-H1993 with
      MET amplification and NCI-H460 with KRAS/PIK3CA mutation human NSCLC cells were
      subcutaneous injected into the athymic nude mice respectively. Mice were randomly
      assigned to treatment with AZD6244, BEZ235, AZD6244 plus BEZ235, or control for 3
      weeks, then all mice were sacrificed and tumor tissues were subjected to western
      blot analyses and immunohistochemical staining. RESULTS: AZD6244 could inhibit
      the tumor growth of NCI-H1993, but slightly inhibit the tumor growth of NCI-1975
      and NCI-H460. Combining AZD6244 with BEZ235 markedly enhanced their antitumor
      effects and without any marked adverse events. Western blot analysis and
      immunohistochemical staining revealed that AZD6244 alone reduced ERK1/2
      phosphorylation, angiogenesis, and tumor cell proliferation. Moreover, MEK1/2
      inhibition resulted in decreased AKT phosphorylation in NCI-H1993 tumor model.
      BEZ235 also inhibited AKT phosphorylation as well as their downstream molecules
      in all three tumor models. The antiangiogenic effects were substantially enhanced
      when the agents were combined, which may due to the reduced expression of matrix
      metallopeptidase-9 in tumor tissues (MMP-9). CONCLUSIONS: In this study, we
      evaluated therapy directed against MEK and PI3K/mTOR in distinct gefitinib
      resistant NSCLC xenograft models. Combining AZD6244 with BEZ235 enhanced their
      antitumor and antiangiogenic effects. We concluded that the combination of a
      selective MEK inhibitor and a PI3K/mTOR inhibitor was effective in suppressing
      the growth of gefitinib-resistant tumors caused by EGFR T790M mutation, MET
      amplification, and KRAS/PIK3CA mutation. This new therapeutic strategy may be a
      practical approach in the treatment of these patients.

PMID- 24939057
TI  - Spectrum of operative childhood intra-articular shoulder pathology.
AB  - PURPOSE: With increased sports participation and medical community awareness,
      there appears to be an increase in pediatric musculoskeletal injuries. Our
      purpose was to identify the intra-articular injury pattern seen within the
      pediatric shoulder. METHODS: A retrospective review was performed at two tertiary
      care children's hospitals between 2008 and 2011 on all patients who underwent
      magnetic resonance imaging (MRI) and subsequent shoulder arthroscopy. Exclusion
      criteria included: girls >14 years old and boys >16 years old. Demographics, MRI
      and arthroscopic findings were recorded. Labral pathology was grouped: Zone I
      (Bankart lesions, 3-6 o'clock for right shoulder), Zone II (posterior labral
      lesions, 6-11 o'clock), Zone III (SLAP lesions, 11-1 o'clock), and Zone IV
      (anatomic variants, 1-3 o'clock). RESULTS: One hundred and fifteen children met
      criteria, mean age 14.4 years (range 8-16). There were 24 girls and 91 boys, with
      70 right shoulders. Of 108 children, labral pathology involved: 72 Zone I (16
      isolated anterior), 56 Zone II (15 isolated posterior), 38 Zone III (four
      isolated superior), and three had an isolated Buford complex. Seventy had more
      than one labral zone injured, and 31 (30 %) had more than two zones injured. Non
      labral pathology included partial rotator cuff tears and humeral avulsions of the
      glenohumeral ligament. CONCLUSION: With 94 % of intra-articular pathology being
      labral tears, the distribution of proportion in children differs from adults;
      moreover, 23 % involved only the posterior or posterosuperior labrum. Treating
      surgeons should be prepared to find anterior tears extending beyond the zone of a
      classic Bankart lesion and an association with C rotator cuff tears.

PMID- 24939058
TI  - Cell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral
      virulence regulators.
AB  - Zinc-finger domain transcriptional regulators regulate a myriad of functions in
      eukaryotes. Interestingly, ancestral versions (MucR) from Alpha-proteobacteria
      control bacterial virulence/symbiosis. Whether virulence regulators can also
      control cell cycle transcription is unknown. Here we report that MucR proteins
      implement a hitherto elusive primordial S->G1 transcriptional switch. After
      charting G1-specific promoters in the cell cycle model Caulobacter crescentus by
      comparative ChIP-seq, we use one such promoter as genetic proxy to unearth two
      MucR paralogs, MucR1/2, as constituents of a quadripartite and homeostatic
      regulatory module directing the S->G1 transcriptional switch. Surprisingly, MucR
      orthologues that regulate virulence and symbiosis gene transcription in Brucella,
      Agrobacterium or Sinorhizobium support this S->G1 switch in Caulobacter. Pan
      genomic ChIP-seq analyses in Sinorhizobium and Caulobacter show that this module
      indeed targets orthologous genes. We propose that MucR proteins and possibly
      other virulence regulators primarily control bacterial cell cycle (G1-phase)
      transcription, rendering expression of target (virulence) genes periodic and in
      tune with the cell cycle. 

PMID- 24939059
TI  - Use of a portable gamma camera for guiding surgical treatment in locally advanced
      breast cancer in a post-neoadjuvant therapy setting.
AB  - The aim of the present study was to assess the feasibility of a portable gamma
      camera (PGC) for guiding surgical treatment in locally advanced breast cancer
      (LABC) after neoadjuvant therapy (NT). Since January 2012, a PGC (Sentinella 102,
      ONCOVISION) has been available in our center. We planned to perform a feasibility
      monocentric prospective study involving 15-20 patients with LABC for assessing
      the diagnostic performance of this PGC after NT (Breast Cancer Surgery-S102).
      Before the surgical treatment and at the end of NT an injection of 99mTc
      Sestamibi (100-150 MBq) was made. Conventional scintimmamography (SMM) and
      Sentinella 102 images were obtained from 18 patients. 10 (55.5 %) patients showed
      a focal uptake of tracer in the breast or lymph nodes before or after the
      surgical excision (on histological specimen), while 8 did not. The histological
      specimen concluded for a complete response to NT in 4 (22.2 %) patients and for a
      partial or no response to treatment in the remnant 14 subjects. The specificity
      and false-negative rate of the Sentinella 102 compared to SMM were 100 % for both
      and 38 % vs. 60 %, respectively. The global diagnostic accuracy of Sentinella 102
      was: 66.7 % (95 % confidence interval: 44.88-88.44 %). The present feasibility
      study shows how a new nuclear imaging device can be useful in the operating
      theatre for guiding a radical surgery approach in patients with LABC after NT.

PMID- 24939054
TI  - MYC cofactors: molecular switches controlling diverse biological outcomes.
AB  - The transcription factor MYC has fundamental roles in proliferation, apoptosis,
      tumorigenesis, and stem cell pluripotency. Over the last 30 years extensive
      information has been gathered on the numerous cofactors that interact with MYC
      and the target genes that are regulated by MYC as a means of understanding the
      molecular mechanisms controlling its diverse roles. Despite significant advances
      and perhaps because the amount of information learned about MYC is overwhelming,
      there has been little consensus on the molecular functions of MYC that mediate
      its critical biological roles. In this perspective, the major MYC cofactors that
      regulate the various transcriptional activities of MYC, including canonical and
      noncanonical transactivation and transcriptional repression, will be reviewed and
      a model of how these transcriptional mechanisms control MYC-mediated
      proliferation, apoptosis, and tumorigenesis will be presented. The basis of the
      model is that a variety of cofactors form dynamic MYC transcriptional complexes
      that can switch the molecular and biological functions of MYC to yield a diverse
      range of outcomes in a cell-type- and context-dependent fashion. 

PMID- 24939060
TI  - Incident comorbidities and all-cause mortality among 5-year survivors of Stage I
      and II breast cancer diagnosed at age 65 or older: a prospective-matched cohort
      study.
AB  - Five-year breast cancer survivors, diagnosed after 65 years of age, may develop
      more incident comorbidities than similar populations free of cancer. We
      investigated whether older breast cancer survivors have a similar comorbidity
      burden 6-15 years after cancer diagnosis to matched women free of breast cancer
      at start of follow-up and whether incident comorbidities are associated with all
      cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage
      breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health
      system-matched women were followed for 10 years. Adjudicated medical record
      review captured prevalent and incident comorbidities during follow-up or until
      death as collected from the National Death Index. Older 5-year breast cancer
      survivors did not acquire incident comorbidities more often than matched women
      free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 %
      confidence interval (95 % CI) 0.93, 1.1]. Adjusted for cohort membership, women
      with incident comorbidities had a higher mortality rate than those without
      incident comorbidities (HR 4.8, 95 % CI 4.1, 5.6). A breast cancer history
      continued to be a hazard for mortality 6-15 years after diagnosis (HR 1.3, 95 %
      CI 1.1, 1.4). We found that older breast cancer survivors who developed
      comorbidities had an increased all-cause mortality rate even after adjusting for
      age and prevalent comorbidity burden. Additionally, survivors acquire
      comorbidities at a rate similar to older women free of breast cancer. These
      results highlight the association between comorbidity burden and long-term
      mortality risk among older breast cancer survivors and their need for appropriate
      oncology and primary care follow-up.

PMID- 24939061
TI  - Influence of boost radiotherapy in patients with ductal carcinoma in situ breast
      cancer: a multicenter, retrospective study in Korea (KROG 11-04).
AB  - To estimate the effect of boost radiotherapy on local recurrence-free survival
      (LRFS) in patients with ductal carcinoma in situ (DCIS) breast cancer. We
      included patients from nine institutions who met the following criteria: having
      Tis, age 18 years or older, having breast conserving surgery (BCS) and
      radiotherapy within 12 weeks after surgery. From 1995 through 2006, 728 patients
      were analyzed retrospectively by the Korean Radiation Oncology Group. All
      patients received whole-breast radiation therapy (WBRT) after BCS. 232 patients
      (31.9 %) also received boost radiation therapy (RT) (median 10 Gy). After median
      follow-up of 82 months, 5-year LRFS was 98.4 % and 10-year LRFS was 95.8 % for
      all patients. There was no statistically significant difference of LRFS between
      the boost and no-boost groups. Nineteen (2.6 %) patients had ipsilateral breast
      recurrences, including 12 of invasive recurrence and 7 DCIS. The presence of the
      HER2 receptor was associated with more invasive recurrences. Nine (1.2 %)
      patients developed contralateral breast cancer, including six invasive breast
      cancer and three DCIS. In the multivariate analysis, only the margin status was a
      significant prognostic factor for LRFS. Boost RT was not associated with further
      improvement of local control in DCIS after BCS and WBRT. HER2 receptor-positive
      patients may need further treatment with the anti-HER2 agents.

PMID- 24939062
TI  - 3D volumetric analysis for planning breast reconstructive surgery.
AB  - Breast reconstruction plays an integral role in the holistic management of breast
      cancer, with assessment of breast volume, shape, and projection vital in planning
      breast reconstruction surgery. Current practice includes two-dimensional (2D)
      photography and visual estimation in selecting ideal volume and shape of breast
      implants or soft-tissue flaps. Other objective quantitative means of calculating
      breast volume have been reported, such as direct anthropomorphic measurements or
      three-dimensional (3D) photography, but none have proven reliably accurate. We
      describe a novel approach to volumetric analysis of the breast, through the
      creation of a haptic, tactile model, or 3D print of scan data. This approach
      comprises use of a single computed tomography (CT) or magnetic resonance imaging
      (MRI) scan for volumetric analysis, which we use to compare to simpler estimation
      techniques, create software-generated 3D reconstructions, calculate, and
      visualize volume differences, and produce biomodels of the breasts using a 3D
      printer for tactile appreciation of volume differential. Using the technique
      described, parenchymal volume was assessed and calculated using CT data. A case
      report was utilized in a pictorial account of the technique, in which a volume
      difference of 116 cm(3) was calculated, aiding reconstructive planning.
      Preoperative planning, including volumetric analysis can be used as a tool to aid
      esthetic outcomes and attempt to reduce operative times in post-mastectomy breast
      reconstruction surgery. The combination of accurate volume calculations and the
      production of 3D-printed haptic models for tactile feedback and operative
      guidance are evolving techniques in volumetric analysis and preoperative planning
      in breast reconstruction.

PMID- 24939064
TI  - Of autophagy and in vivo pancreatic carcinogenesis: the p53 status matters!
AB  - Autophagy is a lysosomal recycling process essential for tissue or cell
      homeostasis. The role of autophagy in cancer is complex with either tumor
      suppressive or pro-carcinogenetic activities. This question has been addressed by
      Kevin Ryan's laboratory by using Kras-driven genetic engineering mouse models in
      order to decipher the involvement of essential Atg5/7 autophagy genes and p53
      status in pancreatic homeostasis and carcinogenetic progression. The authors show
      that combined loss of autophagy and p53 dramatically promotes progression from
      early Pancreatic Intraepithelial Neoplasia (PanIN) lesions towards adenocarcinoma
      and alters the cellular metabolism with an enrichment of anabolic pathway that
      can fuel the tumor growth. 

PMID- 24939065
TI  - Extracardiac findings on coronary CT angiography: a systematic review.
AB  - Coronary computed tomography angiography (CCTA) is of growing importance in
      noninvasive diagnosis of coronary artery diseases. The CT data allow evaluation
      not only of coronary arteries but also of adjacent anatomical territories. Our
      objective was to review, to analyze, and to quantify the spectrum and the
      prevalence of extracardiac findings (ECF) in CCTA. Therefore, we searched
      MEDLINE, EMBASE, and ISI Web of Science. Prior to quantitative analysis, we
      categorized the ECF of all included studies into clinically significant and
      clinically non-significant findings. First, we calculated the average prevalences
      of ECF and clinically significant ECF performing a meta-analysis for proportions
      using the double arcsine transformation. Second, we analyzed the spectrum and
      location of clinically significant ECF. Third, we identified ECF of acutely life
      threatening potential as well as malignancies and calculated their prevalences.
      Thirteen studies with a total of 11,703 patients were found to meet the inclusion
      criteria. The average prevalence of overall ECF was 41.0% (95% confidence
      interval [95% CI]: 27, 56; P < .0001) and 16.0% (95% CI (9, 24; P < .0001) for
      clinically significant ECF. Clinically significant ECF were most commonly
      detected in the lungs (50.2%), the abdomen (26.7%), the vessels (13.1%), the
      mediastinum (3.6%), and in other adjacent anatomical territories (6.4%). The
      prevalence of acutely life-threatening and malignant ECF accounted for 2.2% (95%
      CI: 1.9, 2.5; P < .0001) and 0.3% (95% CI: 0.2-0.4; P < .0001), respectively. In
      conclusion, clinically significant and acutely life-threatening ECF are common.
      Reading CCTA for ECF may lead to earlier detection of relevant disease.
      CONCLUSION: Clinically significant and acutely life-threatening ECF are common.
      Reading CCTA for ECF may lead to earlier detection of relevant disease.

PMID- 24939063
TI  - Gut microbiota, probiotics and diabetes.
AB  - Diabetes is a condition of multifactorial origin, involving several molecular
      mechanisms related to the intestinal microbiota for its development. In type 2
      diabetes, receptor activation and recognition by microorganisms from the
      intestinal lumen may trigger inflammatory responses, inducing the phosphorylation
      of serine residues in insulin receptor substrate-1, reducing insulin sensitivity.
      In type 1 diabetes, the lowered expression of adhesion proteins within the
      intestinal epithelium favours a greater immune response that may result in
      destruction of pancreatic beta cells by CD8+ T-lymphocytes, and increased
      expression of interleukin-17, related to autoimmunity. Research in animal models
      and humans has hypothesized whether the administration of probiotics may improve
      the prognosis of diabetes through modulation of gut microbiota. We have shown in
      this review that a large body of evidence suggests probiotics reduce the
      inflammatory response and oxidative stress, as well as increase the expression of
      adhesion proteins within the intestinal epithelium, reducing intestinal
      permeability. Such effects increase insulin sensitivity and reduce autoimmune
      response. However, further investigations are required to clarify whether the
      administration of probiotics can be efficiently used for the prevention and
      management of diabetes. 

PMID- 24939066
TI  - Multicenter Evaluation Of Coronary Dual-Source CT angiography in patients with
      intermediate Risk of Coronary Artery Stenoses (MEDIC): study design and
      rationale.
AB  - BACKGROUND: The diagnostic performance of multidetector row CT to detect coronary
      artery stenosis has been evaluated in numerous single-center studies, with only
      limited data from large cohorts with low-to-intermediate likelihood of coronary
      disease and in multicenter trials. The Multicenter Evaluation of Coronary Dual
      Source CT Angiography in Patients with Intermediate Risk of Coronary Artery
      Stenoses (MEDIC) trial determines the accuracy of dual-source CT (DSCT) to
      identify persons with at least 1 coronary artery stenosis among patients with low
      to-intermediate pretest likelihood of disease. METHODS: The MEDIC trial was
      designed as a prospective, multicenter, international trial to evaluate the
      diagnostic performance of DSCT for the detection of coronary artery stenosis
      compared with invasive coronary angiography. The study includes 8 sites in
      Germany, India, Mexico, the United States, and Denmark. The study population
      comprises patients referred for a diagnostic coronary angiogram because of
      suspected coronary artery disease with an intermediate pretest likelihood as
      determined by sex, age, and symptoms. All evaluations are performed by blinded
      core laboratory readers. RESULTS: The primary outcome of the MEDIC trial is the
      accuracy of DSCT to identify the presence of coronary artery stenoses with a
      luminal diameter narrowing of 50% or more on a per-vessel basis. Secondary
      outcome parameters include per-patient and per-segment diagnostic accuracy for
      50% stenoses and accuracy to identify stenoses of 70% or more. Furthermore,
      secondary outcome parameters include the influence of heart rate, Agatston score,
      body weight, body mass index, image quality, and diagnostic confidence on the
      accuracy to detect coronary artery stenoses >50% on a per-vessel basis.
      CONCLUSION: The results of the MEDIC trial will assess the clinical utility of
      coronary CT angiography in the evaluation of patients with intermediate pretest
      likelihood of coronary artery disease.

PMID- 24939067
TI  - A novel application of CT angiography to detect extracoronary vascular
      abnormalities in patients with spontaneous coronary artery dissection.
AB  - BACKGROUND: Spontaneous coronary artery dissection (SCAD) is associated with
      extracoronary vascular abnormalities, which depending on type and location may
      warrant treatment or provide additional diagnostic or prognostic information
      about this uncommon entity. Fibromuscular dysplasia (FMD), aneurysms, and
      dissections have been detected in multiple vascular territories by magnetic
      resonance angiography, CT angiography (CTA), and catheter angiography. The
      optimal modality to detect extracoronary vascular abnormalities is unknown. We
      highlight the technique and feasibility of a novel CTA protocol to detect
      extracoronary vascular abnormalities in these patients, incorporating patient
      safety and convenience. METHODS: The complete CTA protocol consisting of a single
      CTA of the neck, chest, abdomen, and pelvis was performed on 39 SCAD outpatients.
      All examinations were performed with 200 mL of low-osmolar contrast agent and
      used radiation dose modulation techniques. Average volume CT dose index was 9 mGy
      for the chest, abdomen, and pelvis portions and 21 mGy for the neck portion.
      Studies were independently reviewed by 2 senior vascular radiologists. RESULTS:
      Two patients had nondiagnostic CTA neck evaluation because of technical
      acquisition errors. Extracoronary vascular abnormalities were detected in 27 of
      39 patients (69%). Catheter angiography detected brachial artery FMD in 1
      patient, a vascular bed not included in the SCAD CTA protocol. Extracoronary
      vascular abnormalities were common, including FMD, aneurysms, dissection, and
      aortic tortuosity, and were seen in the iliac (36%), carotid and/or vertebral
      (31%), splanchnic (10%), and renal (26%) arteries and in the thoracic and/or
      abdominal aorta (10%). CONCLUSIONS: The frequency of extracoronary vascular
      abnormalities and extent of territories identified the CTA protocol in our cohort
      are high. A tailored CTA may be the optimal imaging technique for detecting
      extracoronary vascular abnormalities in patients with suspected underlying
      vasculopathy. Although the clinical significance of extracoronary vascular
      abnormalities remains unclear, detection of these abnormalities has identified
      patients in whom cerebral imaging and serial monitoring have been recommended.

PMID- 24939068
TI  - Overestimation of pretest probability of coronary artery disease by Duke clinical
      score in patients undergoing coronary CT angiography in a Japanese population.
AB  - BACKGROUND: The Duke clinical score (DCS) is commonly used to estimate the
      pretest probability of coronary artery disease (CAD). However, the criterion was
      developed in a population undergoing catheter angiography. OBJECTIVE: To test the
      hypothesis that DCS overestimates the CAD probability when applied to patients
      evaluated with coronary CT angiography (CCTA). A second objective is to compute
      an adjustment of the calculated DCS to apply to this population. METHODS: The DCS
      was calculated for the 3996 consecutive CCTA studies (February 2009 to April
      2013) performed for symptomatic patients with no known CAD. Performance of the
      DCS for the detection of CAD was evaluated by the area under the receiver
      operating characteristic curve. Using the training cohort (n = 2789), a linear
      regression line between the calculated probability and the observed prevalence of
      CAD identified a modified DCS cutoff for a better risk categorization; this was
      internally validated by a separate cohort (n = 1207). RESULTS: The DCS showed a
      good discrimination (area under the receiver operating characteristic curve =
      0.71) for the detection of CAD (prevalence = 23.3%). The calibration analysis
      showed an overall 2.4-fold overestimation by DCS with a DCS < 23% corresponding
      to the low-risk category (ie, observed prevalence of CAD < 10%). There was no
      appropriate DCS cutoff to define high-risk category (ie, prevalence > 90%). The
      validation cohort showed a prevalence of 9.4% when DCS < 23% was used to define
      low risk. CONCLUSION: Among patients who underwent CCTA, DCS overestimated the
      pretest probability by at least 2-fold; the DCS < 23% should define the lower
      risk probability. The DCS poorly identifies high-risk population and thus
      development of new CCTA-based criteria is warranted.

PMID- 24939069
TI  - CT dose reduction using prospectively triggered or fast-pitch spiral technique
      employed in cardiothoracic imaging (the CT dose study).
AB  - OBJECTIVES: To establish current radiation dose levels with contemporary scanners
      capable of prospectively triggered or high-pitch spiral scan modes to previous
      generation scanners among patients evaluated for coronary artery disease,
      pulmonary embolism, aortic disease, and "triple rule out" in a large population
      of patients at multiple centers. BACKGROUND: Previous small-scale studies with
      carefully controlled scan protocols report that CT scanners that facilitate
      prospectively triggered scanning and provide high-pitch spiral CT scan modes
      drastically lower radiation doses. However, diagnostic reference levels should be
      selected by medical bodies on the basis of large surveys of representative sites
      and reviewed at appropriate time intervals. METHODS: Scan data including dose and
      image quality parameters were collected retrospectively from 64 slice scanners
      (control) and prospectively after sites installed 128-slice dual-source scanners
      with high-pitch capability (study). Protocol selection was purposely not
      specified to survey "real world" results. Blinded quantitative image analysis was
      performed on every fifth scan. RESULTS: From April 2011 to March 2012, 2085
      patients at 9 sites completed the study: 1051 coronary artery disease (509
      control, 542 study), 528 pulmonary embolism (267 control, 261 study), 419 aortic
      disease (268 control, 151 study), and 87 triple rule out (53 control, 34 study).
      There was a significant reduction in median dose-length product (DLP) from 669
      mGy ? cm (interquartile range [IQR]: 419-1026 mGy ? cm) in the control group to
      260 mGy ? cm (IQR: 159-441 mGy ? cm) in the study group, a reduction by 61% (P <
      .0001) and was lower in all categories. No significant differences were noted in
      image quality. CONCLUSION: Use of advanced scanners facilitating prospectively
      triggered or high-pitch spiral scan modes results in marked dose reduction across
      a variety of cardiovascular studies, with no compromise in image quality. These
      findings may contribute to new target dose recommendations in societal
      guidelines.

PMID- 24939070
TI  - Automated quantification of epicardial adipose tissue (EAT) in coronary CT
      angiography; comparison with manual assessment and correlation with coronary
      artery disease.
AB  - BACKGROUND: Epicardial adipose tissue (EAT) is emerging as a risk factor for
      coronary artery disease (CAD). OBJECTIVE: The aim of this study was to determine
      the applicability and efficiency of automated EAT quantification. METHODS: EAT
      volume was assessed both manually and automatically in 157 patients undergoing
      coronary CT angiography. Manual assessment consisted of a short-axis-based manual
      measurement, whereas automated assessment on both contrast and non-contrast
      enhanced data sets was achieved through novel prototype software. Duration of
      both quantification methods was recorded, and EAT volumes were compared with
      paired samples t test. Correlation of volumes was determined with intraclass
      correlation coefficient; agreement was tested with Bland-Altman analysis. The
      association between EAT and CAD was estimated with logistic regression. RESULTS:
      Automated quantification was significantly less time consuming than automated
      quantification (17 +/- 2 seconds vs 280 +/- 78 seconds; P < .0001). Although
      manual EAT volume differed significantly from automated EAT volume (75 +/- 33
      cm(3) vs 95 +/- 45 cm(3); P < .001), a good correlation between both assessments
      was found (r = 0.76; P < .001). For all methods, EAT volume was positively
      associated with the presence of CAD. Stronger predictive value for the severity
      of CAD was achieved through automated quantification on both contrast-enhanced
      and non-contrast-enhanced data sets. CONCLUSION: Automated EAT quantification is
      a quick method to estimate EAT and may serve as a predictor for CAD presence and
      severity.

PMID- 24939071
TI  - Prevalence of noncardiac findings in computed tomography angiography before
      transcatheter aortic valve replacement.
AB  - OBJECTIVE: This study sought to determine the prevalence of significant and
      nonsignificant noncardiac findings in patients undergoing preprocedural dual
      source CT (DSCT) before transcatheter aortic valve implantation (TAVI). METHODS:
      Patients (n = 204; aged, 80.5 +/- 5.1 years; 106 men) underwent preprocedural
      DSCT of the thoracoabdominal aorta and the pelvic arterial vessels. Noncardiac
      findings were recorded and categorized as nonsignificant (group A), incidental
      findings requiring follow-up examinations (group B), and significant findings
      with a demand for clinical treatment (group C). RESULTS: In 60 of 204 DSCT
      examinations (29.4%) no noncardiac findings were observed. Of the remaining 144
      examinations (70.6%), 260 had noncardiac findings; 35 of 204 patients (17.1%) had
      a total of 37 clinically significant noncardiac findings. Eight malignancies were
      detected; 5 of them were incidentally diagnosed on DSCT and changed patient
      management. A total of 223 nonsignificant findings were observed in 116 of 204
      patients (56.9%; group A), the most frequent findings were pleural effusions or
      colorectal diverticulosis. The prevalence of incidental and significant findings
      on DSCT before TAVI increased with patient age (r(2) = 0.69; P = .01).
      CONCLUSION: Significant noncardiac findings are common in patients referred to
      routine preprocedural DSCT for planning TAVI (17.1%).

PMID- 24939073
TI  - Analysis of myocardial perfusion from vasodilator stress computed tomography:
      does improvement in image quality by iterative reconstruction lead to improved
      diagnostic accuracy?
AB  - BACKGROUND: Iterative reconstruction (IR) in cardiac CT has been shown to improve
      confidence of interpretation of noninvasive coronary CT angiography (CTA).
      OBJECTIVE: We hypothesized that IR would also improve the quality of vasodilator
      stress coronary CT images acquired with low tube voltage to assess myocardial
      perfusion and the accuracy of the detection of perfusion abnormalities by using
      quantitative 3-dimensional (3D) analysis. METHODS: We studied 39 consecutive
      patients referred for coronary CTA (256-slice scanner; Philips), who underwent
      additional imaging (100 kV, prospective gating) with regadenoson (0.4 mg;
      Astellas). Stress images were reconstructed with different algorithms: filtered
      back projection (FBP) and IR (iDose; Philips). Image quality was quantified by
      signal-to-noise and contrast-to-noise ratios in the blood pool and the
      myocardium. Then, FBP and separately IR images were analyzed with custom 3D
      analysis software to quantitatively detect perfusion defects. Accuracy of
      detection was compared with perfusion abnormalities predicted by coronary
      stenosis >50% on coronary CTA. RESULTS: Five patients with image artifacts were
      excluded. In the remaining 34 patients, both signal-to-noise and contrast-to
      noise ratios increased with IR, indicating improvement in image quality compared
      with FBP. For 3D perfusion analysis, 10 patients with normal coronary arteries
      were used as a reference to correct for x-ray attenuation variations in normal
      myocardium. In the remaining 24 patients, reduced noise levels in the IR images
      compared with FBP resulted in tighter attenuation distribution and improved
      detection of perfusion abnormalities. CONCLUSION: IR significantly improves image
      quality on regadenoson stress CT images acquired with low tube voltage, leading
      to improved 3D quantitative evaluation of myocardial perfusion.

PMID- 24939074
TI  - Diagnosis of left ventricular pseudoaneurysm by cardiac CT angiography.
AB  - We present a case of a patient with left ventricular pseudoaneurysm which was not
      noted on transthoracic echocardiography but incidentally detected by CT
      angiography in preparation of ablation therapy for ventricular tachycardia. The
      patient underwent successful surgical repair of the pseudoaneurysm. The case
      illustrates the utility of CT angiography for the diagnosis of this rare, but
      hazardous condition. 

PMID- 24939072
TI  - Dual-energy computed tomography imaging to determine atherosclerotic plaque
      composition: a prospective study with tissue validation.
AB  - BACKGROUND: Identifying vulnerable coronary plaque with coronary CT angiography
      is limited by overlap between attenuation of necrotic core and fibrous plaque.
      Using x-rays with differing energies alters attenuation values of these
      components, depending on their material composition. OBJECTIVES: We sought to
      determine whether dual-energy CT (DECT) improves plaque component discrimination
      compared with single-energy CT (SECT). METHODS: Twenty patients underwent DECT
      and virtual histology intravascular ultrasound (VH-IVUS). Attenuation changes at
      100 and 140 kV for each plaque component were defined, using 1088 plaque areas co
      registered with VH-IVUS. Hounsfield unit thresholds that best detected necrotic
      core were derived for SECT (conventional attenuation values) and for DECT (using
      dual-energy indices, defined as difference in Hounsfield unit values at the 2
      voltages/their sum). Sensitivity of SECT and DECT to detect plaque components was
      determined in 77 segments from 7 postmortem coronary arteries. Finally, we
      examined 60 plaques in vivo to determine feasibility and sensitivity of clinical
      DECT to detect VH-IVUS-defined necrotic core. RESULTS: In contrast to
      conventional SECT, mean dual-energy indices of necrotic core and fibrous tissue
      were significantly different with minimal overlap of ranges (necrotic core, 0.007
      [95% CI, -0.001 to 0.016]; fibrous tissue, 0.028 [95% CI, 0.016-0.050]; P <
      .0001). DECT increased diagnostic accuracy to detect necrotic core in postmortem
      arteries (sensitivity, 64%; specificity, 98%) compared with SECT (sensitivity,
      50%; specificity, 94%). DECT sensitivity to detect necrotic core was lower when
      analyzed in vivo, although still better than SECT (45% vs 39%). CONCLUSIONS: DECT
      improves the differentiation of necrotic core and fibrous plaque in ex vivo
      postmortem arteries. However, much of this improvement is lost when translated to
      in vivo imaging because of a reduction in image quality.

PMID- 24939075
TI  - Detection of right ventricle thrombosis in patient with Ebstein anomaly of
      tricuspid valve after Fontan procedure by CT.
AB  - A case of a 9-year-old boy with a severe form of Ebstein anomaly who underwent a
      fenestrated Fontan procedure and exclusion of the tricuspid valve is reported. CT
      demonstrated the presence of the right ventricular thrombus which was first found
      on echocardiography and confirmed perioperatively. 

PMID- 24939076
TI  - Lipomatous hypertrophy presenting as superior vena cava syndrome.
AB  - We report a rare case of invasive lipomatous hypertrophy of the interatrial
      septum presenting as superior vena cava syndrome requiring surgical resection.
      Lipomatous hypertrophy of the interatrial septum is a common incidental finding
      and is thought to be a relatively benign condition. Classically, its appearance
      on cardiac computed tomography is primarily fatty with low attenuation, sharp
      margins and minimal enhancement, involving the interatrial septum with relative
      sparing of the fossa ovalis. In masses of unclear etiology or in rare, extensive
      cases resulting in cavity obstruction, such as ours, cardiac computed tomography
      provides complementary information to define tumor extent and characterize
      classic mass features facilitating diagnosis and management. 

PMID- 24939077
TI  - PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles
      mediated hTERT siRNA delivery for anticancer therapy.
AB  - Lack of safe and effective delivery vehicle is the main obstacle for siRNA
      mediated cancer therapy. In this study, we synthesized a pH-sensitive polymer of
      PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged
      hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery
      through a single-step self-assembly method in aqueous condition. The formed
      nanoparticles with charge of around -8.25 mv and average diameter of 102.1 nm
      exhibited efficient siRNA encapsulation and enhanced colloidal and serum
      stability. The test in vitro indicated that the nanoparticles entered into HepG2
      cells by endocytosis, and achieved endosomal escape of siRNA effectively due to
      the pH-responsive disassembly of nanoparticles and dissolution of CaP in the
      endosome. Reporter gene silencing assay showed that luciferase siRNA delivered by
      the anionic nanoparticles could achieve gene silencing efficacy comparable to
      that of conventional Lipofectamine 2000. Additionally, dramatic hTERT knockdown
      mediated by the anionic nanoparticles transfection induced significant apoptosis
      of HepG2 cells in vitro. After intravenous injection in tumor-bearing BALB/c nude
      mice, the nanoparticles specifically accumulated into tumor regions by EPR
      effect, leading to efficient and specific gene silencing sequentially. Most
      importantly, the nanoparticles carrying hTERT siRNA inhibited tumor growth
      significantly via silencing hTERT expression and inducing cells apoptosis in
      HepG2 tumor xenograft. Moreover, comprehensive safety studies of the
      nanoparticles confirmed their superior safety both in vitro and in vivo. We
      concluded that the PEG-CMCS/CaP hybrid anionic nanoparticles possessed potential
      as a safe and effective siRNA delivery system for anticancer therapy. 

PMID- 24939078
TI  - Growth-inhibiting and apoptosis-inducing activities of Myricanol from the bark of
      Myrica rubra in human lung adenocarcinoma A549 cells.
AB  - Myrica rubra (Lour.) Sieb. Et Zucc. is a myricaceae Myrica plant. It is a
      subtropical fruit tree in China and other Asian countries. The bark of M. rubra
      is used in Chinese folk medicine because of its antibacterial, antioxidant, anti
      inflammatory, and anticancer activities. However, the mechanisms underlying such
      activities remain unclear. This study investigated whether or not Myricanol
      extracted from M. rubra bark elicits anti-cancer effects on human lung
      adenocarcinoma A549 cells by inducing apoptosis in vivo. Myricanol was extracted
      from M. rubra bark through system solvent extraction and silica gel layer column
      separation. The results of tritiated thymidine assay, colony formation assay, and
      flow cytometry indicated that Myricanol inhibited the growth of A549 cells. The
      effects of Myricanol on the expression of key apoptosis-related genes in A549
      cells were evaluated by quantitative PCR and Western blot analyses. Myricanol
      significantly inhibited the growth of A549 cells in a dose-dependent manner, with
      a half maximal inhibitory concentration of 4.85 MUg/ml. Myricanol significantly
      decreased colony formation and induced A549 cell apoptosis. Myricanol upregulated
      the expression of Caspase-3, Caspase-9, Bax, and p21 and downregulated the
      expression of Bcl-2 at the mRNA and protein levels. These changes were associated
      with apoptosis. Based on these results, we propose that Myricanol elicits growth
      inhibitory and cytotoxic effects on lung cancer cells. Therefore, Myricanol may
      be a clinical candidate for the prevention and treatment of lung cancer.

PMID- 24939080
TI  - Preservation of the accessory renal arteries after endovascular repair of common
      iliac artery aneurysm using kissing stent grafts.
AB  - Exclusion of the accessory renal arteries (ARAs) is required during endovascular
      aneurysm repair if they arise from the sealing zone or aneurysm sac. Here, we
      report a case of successful endovascular treatment for a common iliac artery
      aneurysm located close to the aortic bifurcation and associated with nephrotic
      syndrome in a 51-year-old man. The bilateral ARAs were successfully preserved
      using kissing stent grafts. During surgery, the proximal ends of endografts
      inserted from the bilateral femoral arteries were adjusted so that they met at
      the same level in the aorta, and simultaneous balloon dilatation was performed.
      This method can be a useful treatment option for common iliac aneurysms in cases
      with large ARAs. 

PMID- 24939081
TI  - [Is controlled drinking a reasonable therapy target for alcohol dependence? For].

PMID- 24939079
TI  - Trends and determinants of costs associated with the inpatient care of diabetic
      foot ulcers.
AB  - OBJECTIVE: The cost of care for diabetic foot ulcers is estimated to be more than
      $1.5 billion annually. The aim of this study was to analyze inpatient diabetic
      foot ulcer cost changes over time and to identify factors associated with these
      costs. METHODS: The Nationwide Inpatient Sample (2005-2010) was queried using the
      International Classification of Diseases, Ninth Revision codes for a primary
      diagnosis of foot ulceration. The primary outcomes were changes in adjusted total
      hospital charges and costs over time. Multivariable analysis was performed to
      assess relative increases (RIs) in hospital charges per patient in 2005 vs 2010
      adjusting for demographic characteristics, income, comorbidities (Charlson
      Comorbidity Index >=3), insurance type, hospital characteristics, diagnostic
      imaging, revascularization, amputation, and length of stay. RESULTS: Overall,
      336,641 patients were admitted with a primary diagnosis of diabetic foot
      ulceration (mean age, 62.9 +/- 0.1 years, 59% male, 61% white race). The annual
      cumulative cost for inpatient treatment of diabetic foot ulcers increased
      significantly from 2005 to 2010 ($578,364,261 vs $790,017,704; P < .001). More
      patients were hospitalized (128.6 vs 152.8 per 100,000 hospitalizations; P <
      .001), and the mean adjusted cost per patient hospitalization increased
      significantly over time ($11,483 vs $13,258; P < .001). The proportion of
      nonelective admissions remained stable (25% vs 23%; P = .32) and there were no
      differences in mean hospital length of stay (7.0 +/- 0.1 days vs 6.8 +/- 0.1
      days; P = .22). Minor (17.9% vs 20.6%; P < .001), but not major amputations (3.9%
      vs 4.2%; P = .27) increased over time. Based on multivariable analysis, the main
      factors contributing to the escalating cost per patient hospitalization included
      increased patient comorbidities (unadjusted mean difference 2005 vs 2010 $3303
      [RI, 1.08] vs adjusted $15,220 [RI, 1.35]), open revascularization (unadjusted
      $15,145 [RI, 1.25] vs adjusted $30,759 [RI, 1.37]), endovascular
      revascularization (unadjusted $17,662 [RI, 1.29] vs adjusted $28.937 [RI, 1.38]),
      and minor amputations (unadjusted $9918 [RI, 1.24] vs adjusted $18,084 [RI,
      1.33]) (P < .001, all). CONCLUSIONS: Hospital charges and costs related to
      diabetic foot ulcers have increased significantly over time despite stable
      hospital length of stay and proportion of emergency admissions. Risk-adjusted
      analyses suggest that this change might be reflective of increasing charges
      associated with a progressively sicker patient population and attempts at limb
      salvage. Despite this, the overall incidence of major amputations remained
      stable.

PMID- 24939083
TI  - Nucleic acid-based assays for the detection of high-risk human papillomavirus: a
      technical review.
AB  - Nucleic acid-based high-risk human papillomavirus (hrHPV) testing is essential to
      contemporary cervical cancer screening. The numbers of commercially available
      assays approved by the US Food and Drug Administration for HPV nucleic acid
      detection have increased, each offering various approaches to analysis. An
      understanding of the methodologies associated with HPV testing is important to
      the practice of laboratory medicine. An overview of instruments, chemistries,
      laboratory workflows, and test limitations associated with current US Food and
      Drug Administration-approved assays is provided.

PMID- 24939082
TI  - Role of miR-146a in human chondrocyte apoptosis in response to mechanical
      pressure injury in vitro.
AB  - MicroRNA (miR)-146a is known to be overexpressed in osteoarthritis (OA). However,
      the role of miR-146a in OA has not yet been fully elucidated. In the present
      study, we applied mechanical pressure of 10 MPa to human chondrocytes for 60 min
      in order to investigate the expression of miR-146a and apoptosis following the
      mechanical pressure injury. Normal human chondrocytes were transfected with an
      miR-146a mimic or an inhibitor to regulate miR-146a expression. Potential target
      genes of miR-146a were predicted using bioinformatics. Moreover, luciferase
      reporter assay confirmed that Smad4 was a direct target of miR-146a. The
      expression levels of miR-146a, Smad4 and vascular endothelial growth factor
      (VEGF) were quantified by quantitative reverse transcription PCR and/or western
      blot analysis. The effects of miR-146a on apoptosis were detected by Annexin V
      fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry. The
      results indicated that mechanical pressure affected chondrocyte viability and
      induced the early apoptosis of chondrocytes. Mechanical pressure injury increased
      the expression levels of miR-146a and VEGF and decreased the levels of Smad4 in
      the chondrocytes. In the human chondrocytes, the upregulation of miR-146a induced
      apoptosis, upregulated VEGF expression and downregulated Smad4 expression. In
      addition, the knockdown of miR-146a reduced cell apoptosis, upregulated Smad4
      expression and downregulated VEGF expression. Smad4 was identified as a direct
      target of miR-146a by harboring a miR-146a binding sequence in the 3'
      untranslated region (3'-UTR) of its mRNA. Furthermore, the upregulation of VEGF
      induced by miR-146a was mediated by Smad4 in the chondrocytes subjected to
      mechanical pressure injury. These results demonstrated that miR-146a was
      overexpressed in our chondrocyte model of experimentally induced human mechanical
      injury, accompanied by the upregulation of VEGF and the downregulation of Smad4
      in vitro. Moreover, our data suggest that miR-146a is involved in human
      chondrocyte apoptosis in response to mechanical injury, and may contribute to the
      mechanical injury of chondrocytes, as well as to the pathogenesis of OA by
      increasing the levels of VEGF and damaging the transforming growth factor (TGF)
      beta signaling pathway through the targeted inhibition of Smad4 in cartilage.

PMID- 24939084
TI  - Efficient simulation of stochastic chemical kinetics with the Stochastic Bulirsch
      Stoer extrapolation method.
AB  - BACKGROUND: Biochemical systems with relatively low numbers of components must be
      simulated stochastically in order to capture their inherent noise. Although there
      has recently been considerable work on discrete stochastic solvers, there is
      still a need for numerical methods that are both fast and accurate. The Bulirsch
      Stoer method is an established method for solving ordinary differential equations
      that possesses both of these qualities. RESULTS: In this paper, we present the
      Stochastic Bulirsch-Stoer method, a new numerical method for simulating discrete
      chemical reaction systems, inspired by its deterministic counterpart. It is able
      to achieve an excellent efficiency due to the fact that it is based on an
      approach with high deterministic order, allowing for larger stepsizes and leading
      to fast simulations. We compare it to the Euler tau-leap, as well as two more
      recent tau-leap methods, on a number of example problems, and find that as well
      as being very accurate, our method is the most robust, in terms of efficiency, of
      all the methods considered in this paper. The problems it is most suited for are
      those with increased populations that would be too slow to simulate using
      Gillespie's stochastic simulation algorithm. For such problems, it is likely to
      achieve higher weak order in the moments. CONCLUSIONS: The Stochastic Bulirsch
      Stoer method is a novel stochastic solver that can be used for fast and accurate
      simulations. Crucially, compared to other similar methods, it better retains its
      high accuracy when the timesteps are increased. Thus the Stochastic Bulirsch
      Stoer method is both computationally efficient and robust. These are key
      properties for any stochastic numerical method, as they must typically run many
      thousands of simulations.

PMID- 24939085
TI  - Patient's experience of treatment for sleep apnoea with a mandibular advancement
      splint.
AB  - BACKGROUND AND AIMS: Obstructive sleep apnoea (OSA) is a well recognised clinical
      disorder in which there is narrowing and repeated collapse of the upper airway
      during sleep resulting in the cessation of breathing. Patients with mild to
      moderate sleep apnoea are often provided with mandibular advancement splint (MAS)
      therapy as a form of first line or definitive treatment. The aims of this audit
      were to evaluate patient satisfaction and success of MAS therapy. METHODS: 93
      patients diagnosed with sleep apnoea and suitable for a splint were recruited
      prospectively at Queen Victoria Hospital, East Grinstead between January 2009 and
      October 2010. A patient satisfaction questionnaire was developed by health
      professionals involved in the care of patients with sleep apnoea and assessed for
      face and content validity and reliability. Participants completed the
      questionnaire six weeks after the splint was fitted. RESULTS: 44% who previously
      experienced snoring now reported no snoring and 47% reported less snoring since
      wearing the MAS appliance. 69% reported complete resolution of sleep apnoea
      symptoms. 37% experienced aching teeth and 33% experienced having a dry throat
      when wearing the appliance. 86% of sleeping partners felt that their quality of
      sleep was improved following their partners treatment. CONCLUSIONS: The standards
      set for each criteria in this audit were met. MAS treatment has a key role to
      play in the management of obstructive sleep apnoea with high rates of patient
      satisfaction and the majority of patients partners reporting a significant
      improvement in their own and their partners sleep quality.

PMID- 24939086
TI  - Cross-column prediction of gas-chromatographic retention indices of saturated
      esters.
AB  - We combine computational molecular descriptors and variables related with the gas
      chromatographic stationary phase into a comprehensive model able to predict the
      retention of solutes in external columns. To explore the quality of various
      approaches based on alternative column descriptors, we analyse the Kovats
      retention indices (RIs) of 90 saturated esters collected with seven columns of
      different polarity (SE-30, OV-7, DC-710, OV-25, XE-60, OV-225 and Silar-5CP).
      Cross-column retention prediction is evaluated on an internal validation set
      consisting of data of 40 selected esters collected with each of the seven
      columns, sequentially excluded from calibration. The molecular descriptors are
      identified by a genetic algorithm variable selection method applied to a large
      set of non-empirical structural quantities aimed at finding the best multi-linear
      quantitative structure-retention relationship (QSRR) for the column OV-25 having
      intermediate polarity. To describe the columns, we consider the sum of the first
      five McReynolds phase constants and, alternatively, the coefficients of the
      corresponding QSRRs. Moreover, the mean RI value for the subset of esters used in
      QSRR calibration or RIs of a few selected compounds are used as column
      descriptors. For each combination of solute and column descriptors, the retention
      model is generated both by multi-linear regression and artificial neural network
      regression. 

PMID- 24939087
TI  - Ultra-preconcentration and determination of selected pharmaceutical and personal
      care products in different water matrices by solid-phase extraction combined with
      dispersive liquid-liquid microextraction prior to ultra high pressure liquid
      chromatography tandem mass spectrometry analysis.
AB  - Pharmaceutical and personal care products (PPCPs) are one of the most important
      classes of emerging contaminants. The potential of ecological and environmental
      impacts associated with PPCPs are of particular concern because they continually
      penetrate the aquatic environment. This work describes a novel ultra
      preconcentration technique for the rapid and highly sensitive analysis of
      selected PPCPs in environmental water matrices at ppt levels. Selected PPCPs were
      rapidly extracted and concentrated from large volumes of aqueous solutions (500
      and 250mL) by solid-phase extraction combined with dispersive liquid-liquid
      microextraction (SPE-DLLME) and then analyzed using UHPLC-MS/MS. Experimental
      parameters were carefully investigated and optimized to achieve the best SPE
      DLLME efficiency and higher enrichment factors. The best results were obtained
      using the ternary mixture acetonitrile/methanol/dichloromethane 3:3:4, v/v/v,
      both as SPE eluent and DLLME extractant/dispersive mixture. DLLME aqueous
      solution (5% NaCl, 10mgL(-1) TBAB) was also modified to improve the extraction
      efficiency of more hydrophilic PPCPs. Under the optimal conditions, an exhaustive
      extraction for most of the investigated analytes (recoveries >70%), with a
      precision (RSD <10%) and very high enrichment factors were attained for different
      aqueous matrices (drinking, sea, river and wastewater). Method detection and
      quantification limits were at very low ppt levels and below 1 and 3ngL(-1),
      respectively, for 15 of selected PPCPs. The proposed analytical procedure offers
      numerous advantages such as the simplicity of operation, rapidity, a high
      enrichment factor and sensitivity. So it is suitable for monitoring and studies
      of occurrence of PPCPs in different environmental compartments. 

PMID- 24939088
TI  - Ion chromatography electrospray ionization mass spectrometry method development
      and investigation of lithium hexafluorophosphate-based organic electrolytes and
      their thermal decomposition products.
AB  - A method based on the coupling of ion chromatography (IC) and electrospray
      ionization mass spectrometry (ESI-MS) for the separation and determination of
      thermal decomposition products of LiPF6-based organic electrolytes is presented.
      The utilized electrolytes, LP30 and LP50, are commercially available and consist
      of 1mol/l LiPF6 dissolved in ethylene carbonate/dimethyl carbonate and ethylene
      carbonate/ethyl methyl carbonate, respectively. For the separation method
      development three ion chromatographic columns with different capacity and
      stationary phase were used and compared. Besides the known hydrolysis products of
      lithium hexafluorophosphate, several new organophosphates were separated and
      identified with the developed IC-ESI-MS method during aging investigations of the
      electrolytes. The chemical structures were elucidated with IC-ESI-MS/MS. 

PMID- 24939089
TI  - OFFGEL fractionation of peptides: where really is your sample?
AB  - Shotgun proteomics of complex samples is generally coupled with at least one
      peptide fractionation step and, to this effect, peptide isoelectric focusing
      (IEF) in immobilized pH gradient (IPG) is one of the most used techniques.
      Fractionation with the OFFGEL 3100 Agilent Technologies apparatus allows the easy
      recovery of peptides that, after focusing, diffuse into the liquid phase above
      the gel strip. In this work we investigate the efficiency of peptide diffusion
      during OFFGEL fractionation and demonstrate that a recovery based only on the
      spontaneous diffusion process is far from being optimal. We show that a simple
      additional extraction step with acetonitrile increases of about 40% the amount of
      material that can be recovered after the focusing. Moreover, we show that the two
      populations of peptides obtained from the passive elution and from the extraction
      process are also qualitatively different and only partially overlapping. 

PMID- 24939090
TI  - Method validation.

PMID- 24939092
TI  - Revisit rates and diagnoses following pediatric tonsillectomy in a large
      multistate population.
AB  - OBJECTIVES/HYPOTHESIS: Investigate the incidence and characteristics of revisits
      following ambulatory pediatric tonsillectomy/adenotonsillectomy. STUDY DESIGN:
      Cross-sectional study using national databases. METHODS: Ambulatory pediatric
      (age <18.0 years) tonsillectomy or adenotonsillectomy cases were extracted from
      the 2010 State Ambulatory Surgery, Emergency Department, and Inpatient databases
      for New York, Florida, Iowa, and California. First and second revisits within the
      14-day postoperative period were tabulated. Diagnoses, procedure codes, and
      mortality were examined. RESULTS: There were 36,221 pediatric
      tonsillectomies/adenotonsillectomies (mean age 7.4 years, 51.4% male). Overall,
      2,740 patients (7.6%) had a revisit after pediatric tonsillectomy; 402 patients
      (1.1%) had a second revisit. Among revisits, 6.3% revisited the ambulatory
      surgery center, 77.5% revisited the emergency department, and 16.2% were
      readmitted as an inpatient. Among all tonsillectomies, bleeding occurred in 2.0%
      and 0.5% within the first and second revisits, respectively. A second revisit had
      a statistically higher association with a primary bleeding diagnosis than the
      first revisit (P < .001). Among all cases, 0.75% underwent a surgical procedure
      for bleeding at a first revisit compared to 0.25% during a second revisit. Acute
      pain was the primary diagnosis in 18.4% and 11.2% of first and second revisits;
      fever/vomiting/dehydration were primary diagnoses in 28.2% and 17.9%,
      respectively. There were two mortalities (0.0055%) within the 14-day
      postoperative interval. CONCLUSIONS: This large-scale analysis describes the
      current rates and diagnoses of revisits, hospital readmission, and surgical
      intervention following ambulatory pediatric tonsillectomy. Many revisits centered
      on pain control and dehydration, suggesting that more adequate symptom control
      may prevent a large proportion of revisits. LEVEL OF EVIDENCE: 2b.

PMID- 24939091
TI  - Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte
      proliferation and dendritic cell functionality.
AB  - Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated
      as an effective mechanism to confer cardio and neuroprotection, especially in
      situations associated to oxidative stress. Pharmacological activation of these
      channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old
      known mitochondrial KATP channel opener, has been proposed as an effective and
      safe treatment for different neurodegenerative diseases, demonstrating efficacy
      in different animal models, including the experimental autoimmune
      encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although
      neuroprotection and modulation of glial reactivity could alone explain the
      positive effects of diazoxide administration in EAE mice, little is known of its
      effects on the immune system and the autoimmune reaction that triggers the EAE
      pathology. The aim of the present work was to study the effects of diazoxide in
      autoimmune key processes related with EAE, such as antigen presentation and
      lymphocyte activation and proliferation. Results show that, although diazoxide
      treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole
      splenocytes it had no effect in isolated CD4(+) T cells. In any case, treatment
      had no impact in lymphocyte activation. Diazoxide can also slightly decrease
      CD83, CD80, CD86 and major histocompatibility complex class II expression in
      cultured dendritic cells, demonstrating a possible role in modulating antigen
      presentation. Taken together, our results indicate that diazoxide treatment
      attenuates autoimmune encephalomyelitis pathology without immunosuppressive
      effect. 

PMID- 24939093
TI  - Synthesis and biological evaluation of certain 3-substituted benzylideneamino-2
      (4-nitrophenyl)quinazolin-4(3H)-one derivatives.
AB  - Certain new 3H-quinazolin-4-one Schiff's bases were synthesized and screened for
      their activities against ulcerative colitis "UC". Their activity against
      phospholipase A2 and protease enzymes was also investigated. Some compounds
      possessed remarkable effect with different potentials against acetic acid-induced
      colitis model in rats. Compound 14 (50 mg/kg) was more effective than
      dexamesathone (0.01 mg/kg). It produced 79.78% protection of control colitis;
      however, compound 13 produced 75.80% protection and was considered as effective
      as dexamesathone with 75.30% protection. The observed results could be explained
      partially by their anti-inflammatory activities which appear as phospholipase A2
      (hGIIA) and/or through protease inhibitor potentials. However, all the compounds
      under test showed preferential inhibition towards hG-IIA type of PLA2 rather than
      DrG-IB with varying degrees. Interestingly, compounds 14, 13, 12 and 11 displayed
      excellent inhibitory activity against phospholipase A2 accompanied by protease
      inhibitory profile. 

PMID- 24939094
TI  - Pistachio (Pistacia vera L.) gum: a potent inhibitor of reactive oxygen species.
AB  - In the present study, in order to evaluate antioxidant and radical scavenging
      properties of Pistachio gum (P-Gum), different bioanalytical methods such as
      DPPH(*) scavenging activity, DMPD(*+) radical scavenging activity, total
      antioxidant activity determination by ferric thiocyanate, reducing ability Fe(3+)
      Fe(2+) transformation, Cuprac and FRAP assays, O2(*-) scavenging by riboflavin
      methionine-illuminate system and ferrous ions (Fe(2+)) chelating activities by
      2,2'-bipyridyl reagent were performed separately. P-Gum inhibited 54.2% linoleic
      acid peroxidation at 10 ug/ml concentration. On the other hand, BHA, BHT, alpha
      tocopherol and trolox, pure antioxidant compounds, indicated inhibition of 80.3%,
      73.5%, 36.2% and 72.0% on peroxidation of linoleic acid emulsion at the same
      concentration, respectively. In addition, all of sample had an effective DPPH(*),
      DMPD(*+) and O2(*-) scavenging, Fe(3+) reducing power by Fe(3+)-Fe(2+)
      transformation and FRAP assay, Cu(2+) reducing ability by Cuprac method and
      Fe(2+) chelating activities.

PMID- 24939096
TI  - Further in vitro biological activity evaluation of amino-, thio- and ester
      derivatives of avarol.
AB  - The acetylcholinesterase inhibitory and/or antitumour activities of amino-, thio-
      and ester-derivatives of avarol selected were evaluated for the first time at in
      vitro conditions. Avarol-3',4'-dithioglycol (1) and avarol-4'
      (3)mercaptopropionic acid (3) were shown to be the best inhibitors of the enzyme
      tested (0.50 ug and IC50 0.05 mM and 0.50 ug and IC50 0.12 mM, respectively),
      while 4'-tryptamine-avarone (9) and avarol-3'-(3)mercaptopropionic acid (2)
      exhibited the highest cytotoxicity against the human breast T-47D cancer cell
      line (IC50 0.66 ug/mL and 1.25 ug/mL, respectively). According to experimental
      data obtained, the sesquiterpenoid hydroquinone structure of bioactive avarol
      derivatives may inspire development of new pharmacologically useful substances to
      be used in the treatment of Alzheimer's disease and/or human breast tumour. 

PMID- 24939095
TI  - 3-benzylidene-4-chromanones: a novel cluster of anti-tubercular agents.
AB  - In a quest for developing novel anti-tubercular agents, a series of 3-benzylidene
      4-chromanones 1a-l were evaluated for growth inhibition of Mycobacterium
      tuberculosis H37Rv. Three promising compounds 1d, g, j emerged as the lead
      compounds with the IC50 and IC90 values of less than 1 ug/mL. Evaluation of the
      potent compounds 1d, g, j and k against Vero monkey kidney cells revealed that
      these compounds are far more toxic to M. tuberculosis than to Vero cells.
      Structure-activity relationships demonstrated that 3-benzylidene-4-chromanones
      are more potent against M. tuberculosis than the related 2-benzylidene
      cycloalkanones and the meta substituted chromanone derivatives are more active
      than their ortho- and para-counterparts. Some guidelines for amplifying the
      project are presented. 

PMID- 24939097
TI  - Recent advances in the discovery of zinc-binding motifs for the development of
      carbonic anhydrase inhibitors.
AB  - In addition to the sulfonamides and their isosteres, recently novel carbonic
      anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) which act by binding to the metal
      ion from the active site were discovered. Based on the X-ray crystal structure of
      the CA II-trithiocarbonate adduct, dithiocarbamates, xanthates and thioxanthates
      were shown to potently inhibit alpha- and beta-CAs. The hydroxamates constitute
      another class of recently studied CAIs both against mammalian and protozoan
      enzymes. Another chemotype for which CA inhibitory properties were recently
      reported is the salicylaldoxime scaffold. X-ray crystal structures were reported
      for CA II complexed with dithiocarbamates and hydroxamates, whereas the xanthates
      and salicylaldoximes were investigated by kinetic measurements and docking
      studies. The dithiocarbamates and the xanthates showed potent antiglaucoma
      activity in animal models of the disease whereas some hydroxamates inhibited the
      growth of Trypanosoma cruzii probably by inhibiting the protozoan CA. 

PMID- 24939099
TI  - 5-membered cyclic hydroxamic acids as HDAC inhibitors.
AB  - The new histone deacylases inhibitors (HDACi) were synthesized in the class of 5
      membered cyclic hydroxamic acids (5-CHA), showing medium size CHA as a new Zn
      binding group. New reaction sequence was proposed for the synthesis of 5-membered
      alkylidene-cyclic-hydroxamic acids starting from butyrolactone. Compound 10c
      showed low uM activity on HeLa cell extracts. From these results, cyclic
      hydroxamic acids will be further investigated to find more potent compounds. 

PMID- 24939098
TI  - Implication of novel thiazolo-thiophene derivative (MCD-KV-10) for management of
      asthma.
AB  - CONTEXT: Asthma is multifaceted disease where many targets contribute towards its
      development and progression. Among these, adenosine receptor subtypes play a
      major role. OBJECTIVE: MCD-KV-10, a novel thiazolo-thiophene was designed and
      evaluated pre-clinically for its implication in management of asthma. MATERIALS
      AND METHODS: This compound showed good affinity and selectivity towards A(2A)/A3
      adenosine receptor (AR) subtypes. Furthermore, MCD-KV-10 was evaluated for in
      vitro lipoxygenase inhibition activity; in vivo mast cell stabilization potential
      and in vivo anti-asthmatic activity was done in ovalbumin-induced airway
      inflammation model in guinea pigs. RESULTS: The compound showed good (>57%)
      inhibition of lipoxygenase enzyme and also effectively protected mast cell
      degranulation (>63%). The compound showed good anti-asthmatic activity as
      inferred from the in vivo studies. DISCUSSION: These results indicate that MCD-KV
      10 has an inhibitory effect on airway inflammation. CONCLUSION: Though, we have
      identified a potential candidate for management of asthma, further mechanistic
      studies are needed.

PMID- 24939100
TI  - The glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-alpha-d
      glucosyl)-sn-glycerol is no inhibitor of the human Myt1 kinase.
AB  - Previously, a glycoglycerolipid isolated from marine algae was reported to be a
      potent and selective inhibitor of the human Myt1 kinase, an enzyme involved in
      cell cycle regulation with great potential as an anti-cancer target. Based on
      that report, a lot of research effort has been invested by several working groups
      to synthesize and derivatize this compound. However, reliable assay data
      confirming the inhibitory potential and the mechanism of action of these
      glycoglycerolipids are missing so far. Here, based on experimental data and
      theoretical considerations, we show that the aforesaid glycoglycerolipid 1,2
      dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-alpha-d-glucosyl)-sn-glycerol is not
      an inhibitor of the human Myt1 kinase. 

PMID- 24939101
TI  - N-omega-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine
      decarboxylase, induces selective growth inhibition and cytotoxicity on human
      cancer cells versus normal cells.
AB  - Many cancer cells have high expression of ornithine decarboxylase (ODC) and there
      is a concerted effort to seek new inhibitors of this enzyme. The aim of the study
      was to initially characterize the inhibition properties, then to evaluate the
      cytotoxicity/antiproliferative cell based activity of N-omega-chloroacetyl-l
      ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a
      reversible competitive ODC inhibitor (Ki = 59 uM) with cytotoxic and
      antiproliferative effects, which were concentration- and time-dependent. The
      EC50,72h of NCAO was 15.8, 17.5 and 10.1 uM for HeLa, MCF-7 and HepG2 cells,
      respectively. NCAO at 500 uM completely inhibited growth of all cancer cells at
      48 h treatment, with almost no effect on normal cells. Putrescine reversed NCAO
      effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity
      is due to ODC inhibition. 

PMID- 24939102
TI  - Synthesis of a novel affinity gel for the purification of carbonic anhydrases.
AB  - A new affinity gel was synthesized for the purification of carbonic anhydrase
      (CA, EC 4.2.1.1) isozymes from erythrocytes. The gel was prepared on a Sepharose
      4B matrix on which a spacer arm based on ethylenediamine was covalently attached
      via CNBr activation, followed by reaction with the CA inhibitor 4-isothiocyanato
      benzenesulfonamide. The derivatized gel incorporated thioureido
      benzenesulfonamide moieties as CA ligand. The binding capacity of the new
      affinity gel was determined at different temperatures, pH values, ionic strengths
      and elution buffers. The maximum binding of various CAs was achieved at 25 
      degrees C with pH 8.5 and ionic strength around 0.4. The overall purifications
      for human (h) hCA I and hCA II were 672- and 580-fold, and with 62 and 43%
      yields, respectively. SDS-polyacrylamide gel electrophoresis showed single bands
      for each purified isozymes, corresponding to a molecular weight of approx. 29
      kDa. This is an easily obtainable, efficient and robust affinity gel, useful for
      the purification of many other alpha-CAs.

PMID- 24939103
TI  - Dipotassium-trioxohydroxytetrafluorotriborate, K2[B3O3F4OH], is a potent
      inhibitor of human carbonic anhydrases.
AB  - The boron heterocyclic compound dipotassium-trioxohydroxytetrafluorotriborate
      (K2[B3O3F4OH]) was investigated as inhibitor of the zinc enzyme, carbonic
      anhydrase (CA, EC 4.2.1.1). Eleven human (h) CA isoforms, hCA I-IV, VA, VI, VII,
      IX and XII-XIV, were included in the investigations. The anion, similar to
      tetraborate or phenylboronic acid, inhibited most of them. hCA III was not
      inhibited by K2[B3O3F4OH], whereas hCA VA, hCA VI, hCA IX and hCA XIII were
      inhibited in the submillimolar range, with KIs of 0.31-0.63 mM. hCA I and II
      (cytosolic, widespread isoforms), hCA IV (membrane-bound isoform), hCA XII (tumor
      associated, transmembrane) and hCA XIV (transmembrane) were much more effectively
      inhibited by this anion, with inhibition constants ranging from 25 to 93 uM. hCA
      VII, a cytosolic enzyme present in the brain and associated to oxidative stress,
      was very effectively inhibited by K2[B3O3F4OH], with a KI of 8.0 uM. We propose
      that K2[B3O3F4OH] binds to the metal ion from the enzyme active site,
      coordinating to the Zn(II) ion monodentately through its B-OH functionality. We
      hypothesize that some of the beneficial antitumor effects reported for
      K2[B3O3F4OH] may be due to the inhibition of CAs present in skin tumors. 

PMID- 24939104
TI  - Synthesis and biological evaluation of new pyrimidine-4-yl-ethanol derivatives as
      ROS1 kinase inhibitors.
AB  - As a part of trials to target ROS1 kinase with potential inhibitors, a novel
      series of pyrimidin-4-yl-ethanol and ethanone derivatives (4a-f, 5a-f, 6a-f and
      7a-f) have been designed based on previously discovered lead compounds KIST301072
      and KIST301080, and synthesized on 4-5 steps according to compounds. The
      structures of the newly synthesized compounds have been confirmed on (1)H-NMR,
      (13)C-NMR and IR. Most of the tested compounds showed ROS1 kinase inhibitory
      activity in micromolar range. 

PMID- 24939105
TI  - Design, synthesis and biological evaluation of naphthostyril derivatives as novel
      protein kinase FGFR1 inhibitors.
AB  - New class of FGFR1 kinase inhibitors with naphthostyril heterocycle has been
      identified. A series of N-phenylnaphthostyril-1-sulfonamides has been synthesized
      and tested in vitro. It was revealed that the most active compound N-(4
      hydroxyphenyl)naphthostyril-1-sulfonamide inhibited FGFR1 with IC50 of 2 uM. In
      our preliminary studies, N-phenylnaphthostyril-1-sulfonamides demonstrated
      selectivity of FGFR1 inhibition and antiproliferative activity on cancer cell
      line. N-phenylnaphthostyril-1-sulfonamides have a good potential for further
      development as anticancer agents.

PMID- 24939106
TI  - In vitro and in vivo antitumor activity of the halogenated boroxine dipotassium
      trioxohydroxytetrafluorotriborate (K2[B3O3F4OH]).
AB  - Dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was listed as a
      promising new therapeutic for cancer diseases. For in vitro and in vivo
      investigation of its antitumor effects 4T1 mammary adenocarcinoma, B16F10
      melanoma and squamous cell carcinoma SCCVII were used. The detailed in vitro
      investigation undoubtedly showed that K2[B3O3F4OH] affects the growth of cancer
      cells. The proliferation of cells depends on the concentration so that aqueous
      solution of K2[B3O3F4OH], the concentrations of 10(-4) M and less, does not
      affect cell growth, but the concentrations of 10(-3) M or more, significantly
      slows cells growth. B16F10 and SCCVII cells show higher sensitivity to the
      cytotoxic effects of K2[B3O3F4OH] compared to 4T1 cells. Under in vivo
      conditions, K2[B3O3F4OH] slows the growth of all three tumors tested compared to
      the control, and the inhibitory effect was most pronounced during the application
      of the substance. There is almost no difference if K2[B3O3F4OH] was applied
      intraperitoneally, intratumor, peroral or as ointment. Addition of 5-FU did not
      further increase the antitumor efficacy of K2[B3O3F4OH]. 

PMID- 24939107
TI  - Risk assessment for patient perpetrated violence: Analysis of three assaults
      against healthcare workers.
AB  - Workplace violence in healthcare settings is a complex topic with many different
      environments in which aggression is sometimes expressed by patients toward those
      entrusted with providing their healthcare. The assessment of violence risk in a
      nursing home containing many patients with organic brain syndrome is quite
      distinct from assessment in forensic psychiatric units, inner city emergency
      rooms, or outpatient pain clinics. Three cases are presented that are composite
      summaries of actual assaults which took place across different hospital settings,
      all within an urban Midwestern city in the United States: (1) an emergency
      department; (2) a psychiatric emergency services (PES) center; (3) a short stay
      (typically 72 hours to 5 days) civil psychiatric inpatient unit. These case
      studies exemplify specific risk factors that violent patients have, depending
      upon the specific healthcare setting where the patient presents. Research is
      cited relevant to all three case studies and how one should assess their risk.
      Lastly, the complexity of this issue is highlighted by a brief discussion of the
      pitfalls entailed in profiling ''the dangerous patient.'' It is demonstrated that
      when violence is expressed by a patient toward a healthcare provider, it is
      usually a maladaptive response, one in which characteristics of that setting and
      behavior of those who work within it must be carefully considered when
      determining what factors precipitated the patient's violent act. 

PMID- 24939108
TI  - Development of the Personal Workplace Safety Instrument for Emergency Nurses.
AB  - BACKGROUND: Much of the research on violence committed by patients and family
      members against healthcare providers in the hospital focus on the frequency and
      severity of incidents plus personal, perpetrator, and hospital characteristics.
      The literature lacks research on those factors that make healthcare providers in
      hospitals feel safe from workplace violence committed by patients and family
      members. OBJECTIVE: The objective of this project is to design an instrument to
      measure the perceptions of personal safety of emergency nurses in the workplace.
      METHODS: To develop the Personal Workplace Safety Instrument for Emergency Nurses
      (PWSI EN) an extensive review of the literature was conducted and recurrent
      themes identified. Informal focus groups of emergency nurses and discussions with
      administrators were conducted to confirm these themes. A review by workplace
      violence experts and a pilot test with emergency nurses was conducted. RESULTS:
      The instrument has 31 Likert-scale items to measure the factors of workplace
      countermeasures, patient-nurse interactions, and administrative and judicial
      support measures. Fifteen demographic questions were developed to measure
      characteristics of the nurse and hospital. Results of the expert panel review
      yielded high content validity (cumulative validity index = 0.98). CONCLUSION: The
      instrument is valid to measure the perceptions of personal safety in the
      workplace with emergency nurses.

PMID- 24939109
TI  - Individual, relationship, workplace, and societal recommendations for addressing
      healthcare workplace violence.
AB  - BACKGROUND: Workplace violence from coworkers, patients, and visitors is a
      problem affecting every occupational group in the health and social service
      sector [1-3]. Workplace violence is demonstrated by coworkers through bullying
      behaviors and by patients and visitors through physical threats and assaults.
      OBJECTIVE: The purpose of this article is to highlight the special issue authors'
      and guest editors' recommendations for protecting healthcare workers from being
      victimized and incurring the negative consequences of having experienced
      workplace violence. METHODS: Recommendations from the special issue were
      categorized and discussed in relation to the Social-Ecological Model and the
      prevention efforts targeting individuals, relationships, communities, and
      society. RESULTS: Individual-level recommendations focused on the personal risk
      reduction for healthcare workers. Relationship-level recommendations addressed
      the problem of bullying between coworkers and physical violence derived from
      patients and visitors. Workplace-level recommendations discussed a multi-faceted
      systems approach to violence management. Societal-level recommendations centered
      on a universal health policy approach. CONCLUSIONS: The use of a model such as
      the Social-Ecological Model can be helpful in planning violence prevention
      efforts in the healthcare setting.

PMID- 24939111
TI  - Economic evaluation of occupational safety preventive measures in a hospital.
AB  - BACKGROUND: When an organization performs an integrated analysis of risks through
      its Occupational Health and Safety Management System, several steps are suggested
      to address the implications of the identified risks. Namely, the organization
      should make a detailed analysis of the monetary impact for the organization of
      each of the preventive measures considered. However, it is also important to
      perform an analysis of the impact of each measure on society (externalities).
      OBJECTIVE: The aim of this paper is to present a case study related to the
      application of the proposed economic evaluation methodology. METHODS: An analysis
      of the work accidents in a hospital has been made. Three of the major types of
      accidents have been selected: needle stings, falls and excessive strain.
      Following the risk assessment, some preventive measures have been designed.
      Subsequently, the Benefit/Cost ratio (B/C) of these measures has been calculated,
      both in financial terms (from the organization's perspective) and in economic
      terms (including the benefits for the worker and for the Society). RESULTS: While
      the financial ratio is only advantageous in some cases, when the externalities
      are taken into account, the B/C ratio increases significantly. CONCLUSIONS: It is
      important to consider external benefits to make decisions concerning the
      implementation of preventive measures in Occupational Health and Safety projects.

PMID- 24939110
TI  - Association between psychosocial job characteristics and sickness absence due to
      low back symptoms using combined DCS and ERI models.
AB  - OBJECTIVE: To evaluate the combined demand-control-support (DCS) and effort
      reward-overcommitment (ERI-OC) stress models in association with sickness absence
      due to low back symptoms (SA-LBS). METHODS: A total of 2,737 blue-collar workers
      recruited from 13 companies in the most populous province (Henan) of China were
      included in the study. Personal and physical job characteristics, psychosocial
      scales of the stress models, and SA-LBS data in the preceding year were collected
      by a self-reported questionnaire and analyzed by a multivariable logistic
      regression model. Tertile exposure levels (low, medium and high) were constructed
      to discriminate a risk level. Odds ratios (OR) with 95% confidence intervals (CI)
      were used as the association with SA-LBS. RESULTS: A large percentage (84.5%) of
      the Chinese workers did not take sick leave after reporting low back symptoms
      during the preceding year. High job demand or medium-high reward was associated
      with SA-LBS. The association of the combined stress models and SA-LBS was not
      evident. CONCLUSIONS: The ERI-OC model appeared to be more predictive of SA-LBS
      than the DCS model in the study population. The advantage of using combined
      stress models for predicting SA-LBS is not evident.

PMID- 24939112
TI  - Workplace violence prevention for nurses on-line course: Program development.
AB  - BACKGROUND: Many entry-level and experienced healthcare professionals have not
      received training in workplace violence prevention strategies. OBJECTIVE: This
      paper describes the development, content, and initial qualitative evaluation of
      an on-line course designed to give healthcare workers an opportunity to acquire
      free workplace violence prevention training while earning free continuing
      education units. METHODS: A group of healthcare violence prevention researchers
      worked via email and face-to-face meetings to decide appropriate content for the
      course. Educational strategies used in the course include: text; video re
      enactments of real-life workplace violence incidents; and videos of nurses
      discussing incidents of violence. Initial evaluation involved a focus group of
      nurses to discuss the course content and navigation. RESULTS: The on-line course
      has thirteen units that take approximately 15 minutes each to complete. The focus
      group participants liked the ''resume-where-you-left-off'' technology that
      enables the user to complete any portion of the course, leave to do something,
      and return to the course where they left off. Participants viewed the ''Nurses'
      Voices'' videos as relevant illustrations of violence that nurses face in their
      workplaces. CONCLUSIONS: The focus group participants considered the course to be
      an effective learning tool for people new to the profession and for those with
      seniority.

PMID- 24939113
TI  - Effects of overhead work involving different heights and distances on neck and
      shoulder muscle activity.
AB  - BACKGROUND: Although overhead work is closely related to musculoskeletal
      disorders, it is difficult to avoid these postures in daily working conditions.
      In industrial tasks that require elevated arm postures above shoulder height,
      flexibility in the location of the task is necessary. OBJECTIVE: This study
      investigated the sternocleidomastoid, upper trapezius, lower trapezius, and
      anterior deltoid, serratus anterior muscle activities during overhead work
      involving four different height and distance locations performed by healthy adult
      participants. METHODS: Eighteen young male right-hand-dominant workers were
      recruited. The right upper trapezius, lower trapezius, serratus anterior,
      anterior deltoid, and sternocleidomastoid muscle activities were measured under
      for overhead work condition (Location 1: overhead work with a height of 10 cm
      above the head of each subject and distance of 15 cm, Location 2: overhead work
      with a height of 10 cm above the head of each subject and distance of 30 cm,
      Location 3: overhead work with a height of 20 cm above the head of each subject
      and distance of 15 cm, Location 4: overhead work with a height of 20 cm above the
      head of each subject and distance of 30 cm). RESULTS: In Location 3, there was
      significantly higher neck extension range of motion compared to Location 1,
      Location 2 and Location 4. In Location 1, the activities of the upper trapezius,
      lower trapezius, serratus anterior, anterior deltoid, and sternocleidomastoid
      muscles were significantly lower than those in Location 3 (p<0.05). In Location
      2, the activities of the upper trapezius, lower trapezius, serratus anterior,
      anterior deltoid, and sternocleidomastoid muscles were significantly lower than
      those in Location 4 (p<0.05). In Location 1, there were significantly lower upper
      trapezius, lower trapezius, serratus anterior, and anterior deltoid muscle
      activities than in Location 2 (p<0.05). In Location 3, there were significantly
      lower upper trapezius, lower trapezius, serratus anterior, and anterior deltoid
      muscle activities than in Location 4 (p<0.05). In Location 1, there was
      significantly higher sternocleidomastoid muscle activity than in Location 2
      (p<0.05). Finally, In Location 3, there was significantly higher
      sternocleidomastoid muscle activity than in Location 4 (p<0.05). CONCLUSIONS:
      Overhead workers should engage in work that involves a low height and near
      distance. Height appears to be a stronger risk factor than distance in overhead
      work.

PMID- 24939114
TI  - Perception of side rollover hazards in a Pennsylvania rural population while
      operating an all-terrain vehicle (ATV).
AB  - BACKGROUND: All-terrain vehicles (ATVs) are unstable on steep and rough terrain,
      and thus, rollover is the most common accident which can result in a high rate of
      fatal outcomes, with higher rates for young and male drivers. OBJECTIVE: This
      paper investigates the ability of rural Pennsylvania ATV drivers to correctly
      evaluate slopes, and the mean slope angle at which the most and least
      conservative drivers indicate a beginning of concern of a roll-over. METHOD: The
      study was conducted using a simulator, a commercial ATV firmly fixed on an
      hydraulically-lifted platform. As the platform was being raised, participants
      were asked to report when they became uncomfortable and then when they would not
      drive across a slope at such an angle. The difference between the reported and
      the actual angles in both conditions were analyzed. RESULTS: Fifty-five
      individuals, mostly male and younger than 20 years, participated in riding on the
      simulator. Between 1/3 and 1/4 of the participants correctly estimated the angle
      while approximately 2/3 of participants overestimated the angles at which they
      felt they would be uncomfortable and they would not drive across. Participants
      began to feel uncomfortable at 15.9+/-5.7 degrees and became so uncomfortable
      that they felt they would not drive at 22.7+/-3.7 degrees. CONCLUSIONS:
      Overestimation of lateral roll angles is the most common result. This is in favor
      of safety when drivers are informed about a slope limit ATVs should not be
      operated on.

PMID- 24939115
TI  - Irregular working hours and fatigue of cabin crew.
AB  - BACKGROUND: Beyond workload and specific environmental factors, flight attendants
      can be exposed to irregular working hours, conflicting with their circadian
      rhythms and having a negative impact in sleep, fatigue, health, social and family
      life, and performance which is critical to both safety and security in flight
      operations. OBJECTIVE: This study focuses on the irregular schedules of cabin
      crew as a trigger of fatigue symptoms in a wet lease Portuguese airline. The aim
      was to analyze: what are the requirements of the cabin crew work; whether the
      schedules being observed and effective resting timeouts are triggering factors of
      fatigue; and the existence of fatigue symptoms in the cabin crew. METHODS: A
      questionnaire has been adapted and applied to a sample of 73 cabin crew-members
      (representing 61.9% of the population), 39 females and 34 males, with an average
      age of 27.68 +/- 4.27 years. RESULTS: Our data indicate the presence of fatigue
      and corresponding health symptoms among the airline cabin crew, despite of the
      sample favorable characteristics. Senior workers and women are more affected.
      CONCLUSIONS: Countermeasures are required. Recommendations can be made regarding
      the fatigue risk management, including work organization, education and awareness
      training programmes and specific countermeasures.

PMID- 24939116
TI  - Stability and reproducibility of semi-quantitative risk assessment methods within
      the occupational health and safety scope.
AB  - BACKGROUND: In many enterprises the semi-quantitative approach turns out to be
      the available and most suitable technique to perform a risk assessment. Despite
      its advantages, we cannot disregard the existing gap in terms of validation of
      this type of applications. OBJECTIVE: This paper reports a study about risk
      assessments' reliability, namely both inter-coder (reproducibility) and intra
      coder (stability) reliability of the semi-quantitative approach. METHODS: This
      study comprised 4 fundamental stages. Data collection relied on free and
      systematized observations and made use of video recording, documental research,
      analysis grids and questionnaires specifically developed for this purpose. A set
      of different analysts were asked to use four semi-quantitative risk assessment
      methods (in two different moments) to estimate and assess six risks identified in
      two tasks accomplished to produce Airbags. The Krippendorff's Alpha Coefficient
      (alpha K) was the agreement measure selected to evaluate both inter-coder and
      intra-coder consensus. RESULTS: The preliminary results revealed a general low
      concordance (alpha K < 0.6) for both reliability evaluations. Apparently there
      are no relevant differences between the risk assessment results obtained by
      individuals with different levels of experience or expertise. CONCLUSIONS: This
      study revealed that the use of the semi-quantitative approach should be done with
      caution.

PMID- 24939117
TI  - Adjustable task lighting: Field study assesses the benefits in an office
      environment.
AB  - BACKGROUND: Lighting is a part of every work task in the office environment, yet
      it is often overlooked. Research links direct and indirect glare to increased
      risk of visual discomfort among office workers with symptoms ranging from dry
      eyes to blurry vision or headaches. Researchers have been primarily concerned
      with those characteristics of task lighting that cause glare including luminance
      level, position (line of sight), and control. It is unknown what the benefits of
      adjustable task lights are and whether or not their use has an effect on
      musculoskeletal comfort or posture. No comprehensive field evaluations of this
      type were found among peer-reviewed, indexed journals. OBJECTIVE: The purpose of
      this study was to assess the ergonomic and calculated utility power consumption
      benefits of adjustable LED task lighting in an office environment using a
      control/intervention experiment design. METHODS: One hundred participants were
      originally recruited and randomly assigned to intervention and control groups.
      Self-reported data was collected on level of eye fatigue, perception of job
      content, intervention usability, and musculoskeletal discomfort. Data was also
      collected on workspace level of illumination and posture during standardized
      tasks (assessed using RULA). RESULTS: Comparing baseline data to follow-up data
      for the intervention group, the use of the adjustable, LED task lights provided
      statistically significant, positive impacts on users' rating of discomfort, eye
      fatigue, perception of job content, and posture between baseline and the short
      term follow up. CONCLUSIONS: Significant benefits to musculoskeletal comfort,
      posture, and visual comfort were documented when participants used the adjustable
      task lights. Participants' assessments of the light's usability, usefulness and
      desirability were positive. There were no negative results found with adjustable
      task light use.

PMID- 24939118
TI  - Neck and shoulder muscle activation patterns among dentists during common dental
      procedures.
AB  - BACKGROUND: Dental practitioners often suffer musculoskeletal disorders (MSDs) in
      the upper extremity due to the static, repetitive and precise nature of work.
      Knowledge regarding muscle activation patterns in that region is essential in
      understanding the mechanism behind the upper extremity MSDs. However, the
      literature review has revealed few studies with such a focus. OBJECTIVE: This
      study aims to examine the inter-relationship of the exertion levels of eleven
      upper extremity muscles during common dental procedures. This provides insights
      into the interactive utilization patterns of the targeted muscles and their
      implications in the development of MSDs. METHODS: Twelve dentists were recruited.
      Electromyography (EMG) signals of sampled muscles were collected for 32 trials,
      i.e. combinations of independent variables (IVs) (and levels): posture (2),
      precision (2), line of vision (4), and grip type (2). Multivariate statistical
      methods were used to analyze the effects of IVs on muscle coactivity patterns.
      RESULTS: MANOVA showed significant main effects and a 2-way interaction between
      precision and grip type. Most notably, the upper trapezius exhibited consistently
      higher utilization than other muscles during a seated posture. CONCLUSIONS:
      Seated postures, preferred by dentists as a way to relieve back stress, may
      contribute to the development of shoulder or neck MSDs due to elevated upper
      trapezius exertions.

PMID- 24939119
TI  - The moderating effect of control over work scheduling and overtime on the
      relationship between workload demands and perceived job risk.
AB  - BACKGROUND: This study investigated the impact of workload demands on perceived
      job risk using the Job Demand-Control model as a research framework. OBJECTIVE:
      The primary objective was to test the hypothesis that employee control over work
      scheduling and overtime would moderate the relationship between workload demands
      and perceived job risk. METHOD: Ninety-six participants working in a variety of
      industries completed measures of workload demands, and of control over work
      scheduling and overtime, and a measure of perceived job risk. RESULTS: Workload
      demands predicted higher perceptions of job risk. However, the results also
      suggest that control over overtime moderated this relationship, where those with
      the combination of high workload demands and low control over overtime reported
      higher levels of perceived risk. The results indicate that the JDC model is
      applicable to safety research. CONCLUSIONS: The results suggest that employee
      control over workload demands is an important variable to consider in terms of
      managing workplace safety. The present study also points to important areas for
      future research to explore in order to further understand the connection between
      demands and safety.

PMID- 24939120
TI  - A multi-agent safety response model in the construction industry.
AB  - BACKGROUND: The construction industry is one of the sectors with the highest
      accident rates and the most serious accidents. A multi-agent safety response
      approach allows a useful diagnostic tool in order to understand factors affecting
      risk and accidents. The special features of the construction sector can influence
      the relationships among safety responses along the model of safety influences.
      OBJECTIVE: The purpose of this paper is to test a model explaining risk and work
      related accidents in the construction industry as a result of the safety
      responses of the organization, the supervisors, the co-workers and the worker.
      METHODS:  SAMPLE: 374 construction employees belonging to 64 small Spanish
      construction companies working for two main companies participated in the study.
      INSTRUMENTS: Safety responses were measured using a 45-item Likert-type
      questionnaire. METHODOLOGY: The structure of the measure was analyzed using
      factor analysis and the model of effects was tested using a structural equation
      model. RESULTS: Factor analysis clearly identifies the multi-agent safety
      dimensions hypothesized. The proposed safety response model of work-related
      accidents, involving construction specific results, showed a good fit.
      CONCLUSIONS: The multi-agent safety response approach to safety climate is a
      useful framework for the assessment of organizational and behavioral risks in
      construction.

PMID- 24939121
TI  - Thermal comfort assessment of a surgical room through computational fluid
      dynamics using local PMV index.
AB  - BACKGROUND: Studies concerning indoor thermal conditions are very important in
      defining the satisfactory comfort range in health care facilities. OBJECTIVE:
      This study focuses on the evaluation of the thermal comfort sensation felt by
      surgeons and nurses, in an orthopaedic surgical room of a Portuguese hospital.
      METHODS: Two cases are assessed, with and without the presence of a person.
      Computational fluid dynamic (CFD) tools were applied for evaluating the predicted
      mean vote (PMV) index locally. RESULTS: Using average ventilation values to
      calculate the PMV index does not provide a correct and enough descriptive
      evaluation of the surgical room thermal environment. As studied for both cases,
      surgeons feel the environment slightly hotter than nurses. The nurses feel a
      slightly cold sensation under the air supply diffuser and their neutral comfort
      zone is located in the air stagnation zones close to the walls, while the
      surgeons feel the opposite. It was observed that the presence of a person in the
      room leads to an increase of the PMV index for surgeons and nurses. That goes in
      line with the empirical knowledge that more persons in a room lead to an
      increased heat sensation. CONCLUSIONS: The clothing used by both classes, as well
      as the ventilation conditions, should be revised accordingly to the amount of
      persons in the room and the type of activity performed.

PMID- 24939122
TI  - A nonlinear dynamics of trunk kinematics during manual lifting tasks.
AB  - BACKGROUND: Human responses at work may exhibit nonlinear properties where small
      changes in the initial task conditions can lead to large changes in system
      behavior. Therefore, it is important to study such nonlinearity to gain a better
      understanding of human performance under a variety of physical, perceptual, and
      cognitive tasks conditions. OBJECTIVE: The main objective of this study was to
      investigate whether the human trunk kinematics data during a manual lifting task
      exhibits nonlinear behavior in terms of determinist chaos. METHODS: Data related
      to kinematics of the trunk with respect to the pelvis were collected using
      Industrial Lumbar Motion Monitor (ILMM), and analyzed applying the nonlinear
      dynamical systems methodology. Nonlinear dynamics quantifiers of Lyapunov
      exponents and Kaplan-Yorke dimensions were calculated and analyzed under
      different task conditions. RESULTS: The study showed that human trunk kinematics
      during manual lifting exhibits chaotic behavior in terms of trunk sagittal
      angular displacement, velocity and acceleration. CONCLUSIONS: The findings
      support the importance of accounting for nonlinear dynamical properties of
      biomechanical responses to lifting tasks.

PMID- 24939123
TI  - Hospital staff registered nurses' perception of horizontal violence, peer
      relationships, and the quality and safety of patient care.
AB  - OBJECTIVE: To test hypotheses from a horizontal violence and quality and safety
      of patient care model: horizontal violence (negative behavior among peers) is
      inversely related to peer relations, quality of care and it is positively related
      to errors and adverse events. Additionally, the association between horizontal
      violence, peer relations, quality of care, errors and adverse events, and nurse
      and work characteristics were determined. PARTICIPANTS: A random sample (n= 175)
      of hospital staff Registered Nurses working in California. METHODS: Nurses
      participated via survey. Bivariate and multivariate analyses tested the study
      hypotheses. RESULTS: Hypotheses were supported. Horizontal violence was inversely
      related to peer relations and quality of care, and positively related to errors
      and adverse events. Including peer relations in the analyses altered the
      relationship between horizontal violence and quality of care but not between
      horizontal violence, errors and adverse events. Nurse and hospital
      characteristics were not related to other variables. Clinical area contributed
      significantly in predicting the quality of care, errors and adverse events but
      not peer relationships. CONCLUSIONS: Horizontal violence affects peer
      relationships and the quality and safety of patient care as perceived by
      participating nurses. Supportive peer relationships are important to mitigate the
      impact of horizontal violence on quality of care.

PMID- 24939124
TI  - Staff perspectives of violence in the emergency department: Appeals for
      consequences, collaboration, and consistency.
AB  - BACKGROUND: Violence committed by patients and their families and visitors
      against Emergency Department staff in the United States is common and detrimental
      to staff well being, morale, and care practices. Hospitals losses occur due to
      decreased staff retention, prestige, and patient and visitor satisfaction.
      OBJECTIVE: The purpose of the baseline survey reported here was to identify and
      describe staff experiences, concerns, and perceptions related to violence and
      abuse perpetrated by patients, family, and non-family visitors in a Level 1
      emergency department. PARTICIPANTS: The survey sample was composed of 41
      registered nurses and 10 paramedics. The majority of the participants (84%, n=
      41) were female and worked full time (82%, n= 41) on the 7P-7A (49%, n= 25)
      shift. METHODS: The cross-sectional mixed-method descriptive design used a survey
      to measure violence experiences and interviews with key informants. Specific
      analytical methods included descriptive and inferential statistics and
      ethnography. RESULTS: The findings are summarized by a model that portrays 1)
      Contributing factors to the development of violence in the ED, 2) maladaptive
      reactions to workplace violence of Cynicism, Concern for focus on customer
      service, and Conflict, and 3) three themes that, depending on their presence or
      absence, serve as barriers or facilitators to violence: Consistency, Consequences
      and Collaboration. CONCLUSIONS: Interventions developed to minimize violence in
      the ED must focus on modifiable risk factors and address what is in the
      department's control including staff education in recognizing escalating anxious
      or aggressive behavior, policy development and implementation, and environmental
      changes.

PMID- 24939125
TI  - Structural barriers at the workplace for employees with vision and locomotor
      disabilities in New Delhi, India.
AB  - BACKGROUND: India, a signatory to the United Nations Convention on the Rights of
      Persons with Disabilities (UNCRPD), has 2.21% of people with disabilities to the
      total population of which 26% are employed (Census 2011 and 2001). Accessibility
      was introduced for the first time in 1995 under The Persons with Disabilities
      (Equal Opportunities, Protection of Rights and Full Participation) Act. Article 9
      of UNCRPD promotes barrier-free environment on an equal basis with others.
      Despite the legislation and the UN convention, structural barriers continue to be
      one of the largest barriers posing concern for PwDs at their workplace.
      OBJECTIVE: To identify various physicall barriers limiting accessibility of PWDs
      in the formal sector in Delhi. METHOD: Quantitative descriptive research design.
      Random sample was drawn. RESULT: Structural barriers create difficulty in
      accessing basic amenities such as canteens, toilets etc. CONCLUSION: Disability
      is a human rights issue. An employee with disability is entitled to dignified
      life. Effective implementation of Article 9 and 27 of UNCRPD will pave a way for
      removing structural barriers at workplace.

PMID- 24939126
TI  - Using the RNAstructure Software Package to Predict Conserved RNA Structures.
AB  - The structures of many non-coding RNA (ncRNA) are conserved by evolution to a
      greater extent than their sequences. By predicting the conserved structure of two
      or more homologous sequences, the accuracy of secondary structure prediction can
      be improved as compared to structure prediction for a single sequence. This unit
      provides protocols for the use of four programs in the RNAstructure suite for
      prediction of conserved structures, Multilign, TurboFold, Dynalign, and PARTS.
      These programs can be run via Web servers, on the command line, or with graphical
      interfaces.

PMID- 24939127
TI  - RNA Secondary Structure Analysis Using RNAstructure.
AB  - RNAstructure is a user-friendly program for the prediction and analysis of RNA
      secondary structure. It is available as a Web server, as a program with a
      graphical user interface, or as a set of command-line tools. The programs are
      available for Microsoft Windows, Macintosh OS X, or Linux. This unit provides
      protocols for RNA secondary structure prediction (using the Web server or the
      graphical user interface) and prediction of high-affinity oligonucleotide biding
      sites to a structured RNA target (using the graphical user interface).

PMID- 24939128
TI  - Employing ProteoWizard to Convert Raw Mass Spectrometry Data.
AB  - After raw data have been captured by mass spectrometers in biological LC-MS/MS
      experiments, they must be converted from vendor-specific binary files to open
      format files for manipulation by most software. This protocol details the use of
      ProteoWizard software for this conversion, taking format features, coding
      options, and vendor particularities into account. This protocol will aid
      researchers in preparing their data for analysis by database search engines and
      other bioinformatics tools.

PMID- 24939130
TI  - Metaproteomics: extracting and mining proteome information to characterize
      metabolic activities in microbial communities.
AB  - Contemporary microbial ecology studies usually employ one or more "omics"
      approaches to investigate the structure and function of microbial communities.
      Among these, metaproteomics aims to characterize the metabolic activities of the
      microbial membership, providing a direct link between the genetic potential and
      functional metabolism. The successful deployment of metaproteomics research
      depends on the integration of high-quality experimental and bioinformatic
      techniques for uncovering the metabolic activities of a microbial community in a
      way that is complementary to other "meta-omic" approaches. The essential, quality
      defining informatics steps in metaproteomics investigations are: (1) construction
      of the metagenome, (2) functional annotation of predicted protein-coding genes,
      (3) protein database searching, (4) protein inference, and (5) extraction of
      metabolic information. In this article, we provide an overview of current
      bioinformatic approaches and software implementations in metaproteome studies in
      order to highlight the key considerations needed for successful implementation of
      this powerful community-biology tool.

PMID- 24939131
TI  - A novel ionic liquid-modified organic-polymer monolith as the sorbent for in-tube
      solid-phase microextraction of acidic food additives.
AB  - A novel ionic liquid-modified organic-polymer monolithic capillary column was
      prepared and used for in-tube solid-phase microextraction (SPME) of acidic food
      additives. The primary amino group of 1-aminopropyl-3-methylimidazolium chloride
      was reacted with the epoxide group of glycidyl methacrylate. The as-prepared new
      monomer was then copolymerized in situ with acrylamide and N,N'
      methylenebisacrylamide in the presence of polyethylene glycol (PEG)-8000 and PEG
      10,000 as porogens. The extraction performance of the developed monolithic
      sorbent was evaluated for benzoic acid, 3-hydroxybenzoic acid, cinnamic acid, 2,4
      dichlorophenoxyacetic acid, and 3-(trifluoromethyl)-cinnamic acid. Such a
      sorbent, bearing hydrophobic and anion-exchange groups, had high extraction
      efficiency towards the test compounds. The adsorption capacities for the analytes
      dissolved in water ranged from 0.18 to 1.74 MUg cm(-1). Good linear calibration
      curves (R(2) > 0.99) were obtained, and the limits of detection (S/N = 3) for the
      analytes were found to be in the range 1.2-13.5 ng mL(-1). The recoveries of five
      acidic food additives spiked in Coca-Cola beverage samples ranged from 85.4 % to
      98.3 %, with RSD less than 6.9 %. The excellent applicability of the ionic liquid
      (IL)-modified monolithic column was further tested by the determination of
      benzoic acid content in Sprite samples, further illustrating its good potential
      for analyzing food additives in complex samples.

PMID- 24939132
TI  - Complexity of fatty acid distribution inside human macrophages on single cell
      level using Raman micro-spectroscopy.
AB  - Macrophages are phagocytic cells which are involved in the non-specific immune
      defense. Lipid uptake and storage behavior of macrophages also play a key role in
      the development of atherosclerotic lesions within walls of blood vessels. The
      allocation of exogenous lipids such as fatty acids in the blood stream dictates
      the accumulation and quantity of lipids within macrophages. In case of an
      overexposure, macrophages transform into foam cells because of the large amount
      of lipid droplets in the cytoplasm. Raman micro-spectroscopy is a powerful tool
      for studying single cells due to the combination of microscopic imaging with
      spectral information. With a spatial resolution restricted by the diffraction
      limit, it is possible to visualize lipid droplets within macrophages. With stable
      isotopic labeling of fatty acids with deuterium, the uptake and storage of
      exogenously provided fatty acids can be investigated. In this study, we present
      the results of time-dependent Raman spectroscopic imaging of single THP-1
      macrophages incubated with deuterated arachidonic acid. The polyunsaturated fatty
      acid plays an important role in the cellular signaling pathway as being the
      precursor of icosanoids. We show that arachidonic acid is stored in lipid
      droplets but foam cell formation is less pronounced as with other fatty acids.
      The storage efficiency in lipid droplets is lower than in cells incubated with
      deuterated palmitic acid. We validate our results with gas chromatography and
      gain information on the relative content of arachidonic acid and its metabolites
      in treated macrophages. These analyses also provide evidence that significant
      amounts of the intracellular arachidonic acid is elongated to adrenic acid but is
      not metabolized any further. The co-supplementation of deuterated arachidonic
      acid and deuterated palmitic acid leads to a non-homogenous storage pattern in
      lipid droplets within single cells. 

PMID- 24939129
TI  - Using PeptideAtlas, SRMAtlas, and PASSEL: Comprehensive Resources for Discovery
      and Targeted Proteomics.
AB  - PeptideAtlas, SRMAtlas, and PASSEL are Web-accessible resources to support
      discovery and targeted proteomics research. PeptideAtlas is a multi-species
      compendium of shotgun proteomic data provided by the scientific community;
      SRMAtlas is a resource of high-quality, complete proteome SRM assays generated in
      a consistent manner for the targeted identification and quantification of
      proteins; and PASSEL is a repository that compiles and represents selected
      reaction monitoring data, all in an easy-to-use interface. The databases are
      generated from native mass spectrometry data files that are analyzed in a
      standardized manner including statistical validation of the results. Each
      resource offers search functionalities and can be queried by user-defined
      constraints; the query results are provided in tables or are graphically
      displayed. PeptideAtlas, SRMAtlas, and PASSEL are publicly available freely via
      the Web site http://www.peptideatlas.org. In this protocol, we describe the use
      of these resources, we highlight how to submit, search, collate and download
      data.

PMID- 24939134
TI  - Polyluminol/hydrogel composites as new electrochemiluminescent-active sensing
      layers.
AB  - This paper reports on electrochemiluminescent sensors and biosensors based on
      polyluminol/hydrogel composite sensing layers using chemical or biological
      membranes as hydrogel matrices. In this work, luminol is electropolymerized under
      near-neutral conditions onto screen-printed electrode (SPE)-supported hydrogel
      films. The working electrode coated with a hydrogel film is soaked in a solution
      containing monomeric luminol units, allowing the monomeric luminol units to
      diffuse inside the porous matrix to the electrode surface where they are
      electropolymerized by cyclic voltammetry (CV). Sensors and enzymatic biosensors
      for H2O2 and choline detection, respectively, have been developed, using choline
      oxidase (ChOD) as a model enzyme. In this case, hydrogel is used both as the
      enzymatic immobilization matrix and as a template for the electrosynthesis of
      polyluminol. The enzyme was immobilized by entrapment in the gel matrix during
      its formation before electropolymerization of the monomer. Several parameters
      have been optimized in terms of polymerization conditions, enzyme loading, and
      average pore size. Using calcium alginate or tetramethoxysilane (TMOS)-based
      silica as porous matrix, H2O2 and choline detection are reported down to
      micromolar concentrations with three orders of magnitude wide dynamic ranges
      starting from 4 * 10(-7) M. Polyluminol/hydrogel composites appear as suitable
      electrochemiluminescence (ECL)-active sensing layers for the design of new
      reagentless and disposable easy-to-use optical sensors and biosensors, using
      conventional TMOS-based silica gel or the more original and easier to handle
      calcium alginate, reported here for the first time in such a configuration, as
      the biocompatible hydrogel matrix. 

PMID- 24939133
TI  - Mass spectrometric studies on effects of counter ions of TMPyP4 on binding to
      human telomeric DNA and RNA G-quadruplexes.
AB  - A comparative study on human telomeric DNA G-quadruplex binding of meso
      5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) between its two salt
      forms, i.e., tetratosylate and tetrachloride, was conducted by using ESI-TOF-MS,
      UV-melting measurement, and molecular modeling methods. Besides cation TMPyP4,
      the tosyl anion was found to bind to human telomeric DNA G-quadruplex with
      multiple binding stoichiometries from 1:1 to 3:1 observed in ESI-TOF-MS spectra,
      indicating that the stabilization activity of TMPyP4 tetratosylate on G
      quadruplex is derived from a synergetic effect of both TMPyP4 cation and tosyl
      anion. A molecular modeling study suggests that a tosyl anion fills up the vacant
      space between TMPyP4 cation and DNA G-quadruplex and thus stabilizes the complex
      by 3.8 kcal/mol. Therefore, it is estimated that TMPyP4 tetratosylate's activity
      might not reflect the real effect of TMPyP4 cation in some bioassays related to G
      quadruplex stabilization. This was verified by the results of less binding
      affinity of TMPyP4 tetrachloride with DNA G-quadruplex obtained from ESI-TOF-MS
      measurement, and of 2.27  degrees C less thermal stabilization of TMPyP4
      tetrachloride for DNA G-quadruplex, compared to its tetratosylate under the same
      conditions. Our study demonstrated the influence of counter ions of TMPyP4 on G
      quadruplex binding, which sheds light on the proper usage of TMPyP4 salt in the
      chemical and biological research associated with G-quadruplex binding.
      Subsequently, the binding of TMPyP4 tetrachloride to human telomeric RNA G
      quadruplexes was studied with ESI-TOF-MS technique. The binding constants of
      TMPyP4 with human telomeric G-quadruplexes indicated that TMPyP4 binds to human
      telomeric RNA G-quadruplex one order of magnitude stronger than DNA counterpart.
      This is a comprehensive mass spectrometric report on binding study of TMPyP4 with
      human telomeric DNA/RNA G-quadruplexes. 

PMID- 24939135
TI  - Excretion kinetics of 13C-urea breath test: influences of endogenous CO2
      production and dose recovery on the diagnostic accuracy of Helicobacter pylori
      infection.
AB  - We report for the first time the excretion kinetics of the percentage dose of
      (13)C recovered/h ((13)C-PDR %/h) and cumulative PDR, i.e. c-PDR (%) to
      accomplish the highest diagnostic accuracy of the (13)C-urea breath test ((13)C
      UBT) for the detection of Helicobacter pylori infection without any risk of
      diagnostic errors using an optical cavity-enhanced integrated cavity output
      spectroscopy (ICOS) method. An optimal diagnostic cut-off point for the presence
      of H. pylori infection was determined to be c-PDR (%) = 1.47 % at 60 min, using
      the receiver operating characteristic curve (ROC) analysis to overcome the "grey
      zone" containing false-positive and false-negative results of the (13)C-UBT. The
      present (13)C-UBT exhibited 100 % diagnostic sensitivity (true-positive rate) and
      100 % specificity (true-negative rate) with an accuracy of 100 % compared with
      invasive endoscopy and biopsy tests. Our c-PDR (%) methodology also manifested
      both diagnostic positive and negative predictive values of 100 %, demonstrating
      excellent diagnostic accuracy. We also observed that the effect of endogenous CO2
      production related to basal metabolic rates in individuals was statistically
      insignificant (p = 0.78) on the diagnostic accuracy. However, the presence of H.
      pylori infection was indicated by the profound effect of urea hydrolysis rate
      (UHR). Our findings suggest that the current c-PDR (%) is a valid and
      sufficiently robust novel approach for an accurate, specific, fast and
      noninvasive diagnosis of H. pylori infection, which could routinely be used for
      large-scale screening purposes and diagnostic assessment, i.e. for early
      detection and follow-up of patients. 

PMID- 24939136
TI  - Validation of a confirmatory method for lipophilic marine toxins in shellfish
      using UHPLC-HR-Orbitrap MS.
AB  - Lipophilic marine toxins are produced by harmful microalgae and can accumulate in
      edible filter feeders such as shellfish, leading to an introduction of toxins
      into the human food chain, causing different poisoning effects. During the last
      years, analytical methods, based on liquid chromatography coupled to tandem mass
      spectrometry (LC-MS/MS), have been consolidated by interlaboratory validations.
      However, the main drawback of LC-MS/MS methods remains the limited number of
      compounds that can be analyzed in a single run. Due to the targeted nature of
      these methods, only known toxins, previously considered during method
      optimization, will be detected. Therefore in this study, a method based on ultra
      high-performance liquid chromatography coupled to high-resolution Orbitrap mass
      spectrometry (UHPLC-HR-Orbitrap MS) was developed. Its quantitative performance
      was evaluated for confirmatory analysis of regulated lipophilic marine toxins in
      shellfish flesh according to Commission Decision 2002/657/EC. Okadaic acid (OA),
      dinophysistoxin-1 (DTX-1), pectenotoxin-2 (PTX-2), azaspiracid-1 (AZA-1),
      yessotoxin (YTX), and 13-desmethyl spirolide C (SPX-1) were quantified using
      matrix-matched calibration curves (MMS). For all compounds, the reproducibility
      ranged from 2.9 to 4.9 %, repeatability from 2.9 to 4.9 %, and recoveries from
      82.9 to 113 % at the three different spiked levels. In addition, confirmatory
      identification of the compounds was effectively performed by the presence of a
      second diagnostic ion ((13)C). In conclusion, UHPLC-HR-Orbitrap MS permitted more
      accurate and faster detection of the target toxins than previously described LC
      MS/MS methods. Furthermore, HRMS allows to retrospectively screen for many
      analogues and metabolites using its full-scan capabilities but also untargeted
      screening through the use of metabolomics software. 

PMID- 24939137
TI  - Evaluation of ultra high-performance [corrected] liquid chromatography columns
      for the analysis of unmodified and antisense oligonucleotides.
AB  - Ultra high-performance [corrected] liquid chromatography has been used for the
      separation and analysis of unmodified and modified antisense oligonucleotides.
      For this reason, we tested various columns of low particle sizes in our analysis
      of unmodified and phosphorothioate oligonucleotides. The influence of both the
      type and concentration of ion-pair reagent on the retention of the studied
      biomolecules was tested. The developed methods were used for separation of
      unmodified oligonucleotides and to determine antisense oligonucleotides in human
      serum samples. The results proved that octadecyl and phenyl columns are the most
      selective in the resolution of oligonucleotides which differ in the position of
      single nucleotides in the sequence. The phenyl column was selected and applied
      for the analysis of phosphorothioate oligonucleotides in serum samples. The
      calibration plots showed good linearity within the test concentration ranges. The
      intra-day CV of the calibration curve slopes was in the range of 1.6 to 4.2 %.
      The limits of detection (LODs) were in the range of 0.11-0.16 MUg mL(-1), while
      the limit of quantification (LOQ) values were between 0.35 and 0.51 MUg mL(-1).

PMID- 24939141
TI  - Primary relapse site pattern in women with triple-negative breast cancer.
AB  - Despite the remarkable improvements in breast cancer (BC) characterization,
      accurate prediction of BC clinical behavior is often still difficult to achieve.
      Some studies have investigated the association between the molecular subtype,
      namely the basal-like BC and the pattern of relapse, however only few
      investigated the association between relapse pattern and immunohistochemical
      defined triple-negative breast cancers (TNBCs). The aim of this study was to
      evaluate the pattern of relapse in patients with TNBC, namely the primary distant
      relapse site. One-hundred twenty nine (129) invasive breast carcinomas with
      follow-up information were classified according to the molecular subtype using
      immunohistochemistry for ER, PgR and Her2. The association between TNBC and
      distant relapse primary site was analyzed by logistic regression. Using
      multivariate logistic regression analysis patients with TNBC displayed only 0.09
      (95% CI: 0.00-0.74; p=0.02) the odds of the non-TNBC patients of developing bone
      primary relapse. Regarding visceral and lymph-node relapse, no differences
      between in this cohort were found. Though classically regarded as aggressive
      tumors, TNBCs rarely development primary relapse in bone when compared to non
      TNBC, a clinical relevant fact when investigating a metastasis of an occult or
      non-sampled primary BC.

PMID- 24939142
TI  - Expression of L-type amino acid transporter 1 in various skin lesions.
AB  - L-type amino acid transporter 1 (LAT1) is a Na(+)-independent neutral amino acid
      transporter that has an essential role in cell proliferation. Although the
      involvement of LAT1 in human carcinogenesis has been investigated by
      immunohistochemistry in various organs, LAT1 expression in skin has not been
      reported yet. Therefore, in the present study, immunohistochemistry for LAT1 was
      performed in 15 keratoacanthoma (KA), 10 seborrheic keratosis, 16 Bowen's
      disease, 11 basal cell carcinoma (BCC), and 9 squamous cell carcinoma (SCC) cases
      as well as 61 normal epidermis as control. It was demonstrated that LAT1
      expression limited to the basal layer was occasionally observed in normal
      epidermis while its expression was significantly decreased in the epithelium of
      seborrheic keratosis and Bowen's disease (P<0.05). By contrast, a significantly
      higher rate of LAT1 expression was observed in the epithelium of KA, BCC, and SCC
      than in normal epidermis (P<0.05). Although LAT1 expression was limited to the
      basal layer or rim of the nests in KA, LAT1 expression was also observed in the
      center of the nests in BCC and SCC (P<0.001). Thus, LAT1 is differentially
      expressed in various skin lesions and may be an especially useful marker to
      distinguish KA from SCC. 

PMID- 24939143
TI  - Communicating diagnostic uncertainty in surgical pathology reports: disparities
      between sender and receiver.
AB  - Surgical pathologists use a variety of phrases to communicate varying degrees of
      diagnostic certainty which have the potential to be interpreted differently than
      intended. This study sought to: (1) assess the setting, varieties and frequency
      of use of phrases of diagnostic uncertainty in the diagnostic line of surgical
      pathology reports, (2) evaluate use of uncertainty expressions by experience and
      gender, (3) determine how these phrases are interpreted by clinicians and
      pathologists, and (4) assess solutions to this communication problem. We
      evaluated 1500 surgical pathology reports to determine frequency of use of
      uncertainty terms, identified those most commonly used, and looked for variations
      in usage rates on the basis of case type, experience and gender. We surveyed 76
      physicians at tumor boards who were asked to assign a percentage of certainty to
      diagnoses containing expressions of uncertainty. We found expressions of
      uncertainty in 35% of diagnostic reports, with no statistically significant
      difference in usage based on age or gender. We found wide variation in the
      percentage of certainty clinicians assigned to the phrases studied. We conclude
      that non-standardized language used in the communication of diagnostic
      uncertainty is a significant source of miscommunication, both amongst
      pathologists and between pathologists and clinicians. 

PMID- 24939144
TI  - A modified GEWF solution is cost-saving and effective for lymph node retrieval in
      resected colorectal carcinoma specimens.
AB  - Lymph node (LN) retrieval is important for proper staging of colorectal
      carcinoma. Although various assistant techniques were recommended to facilitate
      LN identification, most of them were unavoidably time-consuming, resource
      intensive and costly. We prepared a modified GEWF solution (RE-GEWF) by use of
      recycled alcohol and a familiar dye, eosin and investigated its efficacy on 55
      colorectal carcinoma specimens. Of the 55 studied cases, 33 of them with <12 LNs
      (Group A) and 22 with >=12 LNs were detected (Group B) before RE-GEWF treatment.
      All were subsequently treated with RE-GEWF for 14-16h and were inspected again
      for LNs. The number of LNs revealed before and after RE-GEWF treatment was 539
      and 476 respectively. The mean number of LNs per cases increased from 9.80+/-6.27
      to 18.43+/-8.77. Twelve accessory LN metastases were found in 9 cases. Upgrade of
      pN stage was only present in 7 of the Group A cases. The results show that RE
      GEWF is as effective as other reported LN revealing solutions. Use of RE-GEWF not
      only can assure the quality of LN detection, but also minimize the cost and
      reduce the release of waste.

PMID- 24939145
TI  - Renal injury induced in alloxan diabetic rats. Role of Mycophenolate Mofetil as
      therapeutic agent.
AB  - BACKGROUND: Renal injury may develop in uncontrolled chronic hyperglycemia due to
      increased oxidative stress and release of pro-inflammatory mediators, leading to
      diabetic complications. METHODS: Mycophenolate Mofetil (MMF) is an
      immunosuppressant drug, an inhibitor of inosine monophosphate dehydrogenase
      (IMPDH), relevant to inflammation processes. MMF effect was tested in alloxan
      diabetic rats on selected parameters like oxidative stress, gene expression of
      tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF
      beta1), in relation to microalbuminuria and renal function. RESULTS: We found
      that the onset of microalbuminuria preceded the increase in serum glucose after
      alloxan treatment. Gene expression of TNF-alpha and TGF-beta1 showed gradual
      increase after one and two weeks of alloxan administration as compared to the
      normal group. MMF administration decreased the gene expression of TNF-alpha and
      TGF-beta1 in kidney tissues, serum glucose, fructosamine, urea, creatinine, C
      reactive protein, malondialdehyde, urinary microalbumin and total protein.
      Histological examination of kidney tissues showed significant improvement in MMF
      treated rats as compared to diabetic control. CONCLUSIONS: MMF modulated renal
      injury of alloxan diabetic rats. Collective data may support its therapeutic
      effect but further clinical trials may be requested.

PMID- 24939147
TI  - Expression of apoptotic proteins in human colorectal cancer and metastatic lymph
      nodes.
AB  - PURPOSE: The aim of this study was to determine the expression of Bak, Bax, Bcl
      2, Bcl-xl and procaspase-3 proteins in colorectal tumor and regional lymph nodes,
      as well as to investigate the correlation between them and with clinicopathologic
      parameters. METHODS: Expression of the examined proteins was evaluated by
      immunohistochemical study. RESULTS: No significant correlation was revealed
      between Bcl-2, Bcl-xl, Bak, Bax and procaspase-3 expressions and age, gender,
      location or size of primary tumor and grade in the main tumor mass or in lymph
      nodes. Additionally, the only association we found was between Bak protein in
      primary tumor and in adjacent metastatic lymph nodes. CONCLUSION: Bcl-2 protein
      seems to exert substantial effects prevention of apoptosis in pT3 CRC with
      positive lymph node involvement, while lower expressions of Bcl-xl proteins
      suggest that it does not play a significant part in the inhibition of apoptosis.

PMID- 24939148
TI  - Malignant pleuropulmonary epithelioid hemangioendothelioma - unusual presentation
      of an aggressive angiogenic neoplasm.
AB  - Epithelioid hemangioendothelioma (EHE) of the lung and pleura are rare tumors.
      Primary pleural EHE are associated with aggressive behavior and poor clinical
      outcome. Recent advances in EHE include the development of immunohistochemical
      markers of vascular differentiation, namely Fli-1, and the identification of a
      specific chromosomal translocation (t(1;3)(p36;q25)). We present a 19 year old
      male patient with a rapidly progressive malignant neoplasm that presented as a
      multinodular lung parenchymal process, with associated pleural effusion and
      thickening. Pathologic examination revealed a pleuropulmonary neoplasm with
      cytologic features including round to oval epithelioid cells with frequent
      cytoplasmic vacuoles. Immunohistochemistry confirmed vascular differentiation of
      tumor cells (CD34, CD31 and Fli-1 positive). While the cytologic features were
      suggestive of EHE, the aggressive nature of the neoplasm, with disseminated
      pleuropulmonary involvement, raised the question of whether the neoplasm should
      be classified as EHE or epithelioid angiosarcoma. Here, we review the
      clinicopathologic characteristics of pleuropulmonary EHE and the overlap between
      malignant EHE and angiosarcoma.

PMID- 24939146
TI  - Thalidomide alleviates acute pancreatitis-associated lung injury via down
      regulation of NFkappaB induced TNF-alpha.
AB  - AIMS: We studied the effect of thalidomide on NFkappaB-induced TNF-alpha in acute
      pancreatitis-associated lung injury in the rat. METHODS: Rats were
      intragastrically administered thalidomide (100mg/kg) daily for 8 days and then
      acute pancreatitis was induced by retrograde infusion of 5% sodium taurocholate
      into the rat biliopancreatic duct. Serum amylase (AMY), blood oxygen partial
      pressure (PaO2), ratios of lung wet/dry weight, and cytoplasmic IkappaBalpha and
      TNF-alpha protein and nuclear NFkappaBp65 protein were measured. Also, lung
      NFkappaBp65 and TNF-alpha mRNA were measured. RESULTS: Compared with the model
      group, the pathological score of the pancreas and lung, serum AMY, ratios of lung
      wet/dry weight, and lung NFkappaBp65 and TNF-alpha mRNA and protein of rats given
      thalidomide were decreased significantly (P<0.01), but PaO2 and IkappaBalpha
      protein was elevated significantly (P<0.01). CONCLUSION: Thalidomide may inhibit
      TNF-alpha expression via down-regulation of the NFkappaB signaling pathway to
      alleviate acute pancreatitis-associated lung injury in rats.

PMID- 24939149
TI  - Pathologic findings in native infective endocarditis.
AB  - BACKGROUND: There are few studies on the histologic findings in native infective
      endocarditis, especially regarding mimics of autoimmune valvulitis. METHODS: We
      prospectively studied 106 surgical specimens from 95 patients with a clinical
      diagnosis of infective endocarditis on native valves, and compared gross and
      histologic findings with culture results, underlying valve disease, risk factors
      and time interval from symptom onset to surgical intervention. RESULTS: There
      were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11
      (10%) multiple valve replacements. Underlying valve disease was present in 26
      (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve
      prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases;
      calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve
      disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease,
      1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with
      streptococcal infection (p = .001). Absence of underlying valve disease was
      associated with intravenous drug abuse (p = .01) and dialysis dependent renal
      disease (p = .006). Intravenous drug abuse was associated with staphylococcal
      infection (p = .03). Vegetations were present in 80 (75%) of cases, and on the
      nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and
      neutrophilic microabscesses were associated with staphylococcal infection (p =
      .03). Epithelioid macrophages with palisading features mimicking necrobiotic
      granulomas were seen in 42 (40%) valves and more frequently associated with
      streptococcal infection (p=.03). As expected, the presence of valve necrosis and
      acute inflammation decreased with an increase in time with respect to symptomatic
      onset. CONCLUSION: Histologic findings that mimic autoimmune inflammation are
      frequent in infective endocarditis and associated with streptococcal infection.
      Risk factors for infective endocarditis include calcific valve disease.

PMID- 24939150
TI  - DAFGA: diversity analysis of functional gene amplicons.
AB  - SUMMARY: Diversity analysis of functional marker genes provides physiological
      insights into microbial guilds that perform an ecologically relevant process.
      However, it is challenging to group functional gene sequences to valid taxonomic
      units, primarily because of differences in the evolutionary rates of individual
      genes and possible horizontal gene transfer events. We developed a python script
      package named DAFGA, which estimates the evolutionary rate of a particular
      functional gene in a standardized manner by relating its sequence divergence to
      that of the 16S rRNA gene. As a result, DAFGA provides gene-specific parameter
      sets for operational taxonomic unit clustering and taxonomic assignment at
      desired rank, and it can be implemented into the diversity measurements offered
      by QIIME. AVAILABILITY AND IMPLEMENTATION: DAFGA is freely available with a
      manual and test data from https://github.com/outbig/DAFGA.

PMID- 24939151
TI  - Literome: PubMed-scale genomic knowledge base in the cloud.
AB  - MOTIVATION: Advances in sequencing technology have led to an exponential growth
      of genomics data, yet it remains a formidable challenge to interpret such data
      for identifying disease genes and drug targets. There has been increasing
      interest in adopting a systems approach that incorporates prior knowledge such as
      gene networks and genotype-phenotype associations. The majority of such knowledge
      resides in text such as journal publications, which has been undergoing its own
      exponential growth. It has thus become a significant bottleneck to identify
      relevant knowledge for genomic interpretation as well as to keep up with new
      genomics findings. RESULTS: In the Literome project, we have developed an
      automatic curation system to extract genomic knowledge from PubMed articles and
      made this knowledge available in the cloud with a Web site to facilitate
      browsing, searching and reasoning. Currently, Literome focuses on two types of
      knowledge most pertinent to genomic medicine: directed genic interactions such as
      pathways and genotype-phenotype associations. Users can search for interacting
      genes and the nature of the interactions, as well as diseases and drugs
      associated with a single nucleotide polymorphism or gene. Users can also search
      for indirect connections between two entities, e.g. a gene and a disease might be
      linked because an interacting gene is associated with a related disease.
      AVAILABILITY AND IMPLEMENTATION: Literome is freely available at
      literome.azurewebsites.net. Download for non-commercial use is available via Web
      services.

PMID- 24939152
TI  - Transynaptic changes evident in peripheral axonal function after acute cerebellar
      infarct.
AB  - The cerebellum has a vital role in fine motor control of the limbs. Consequently,
      downstream changes in peripheral axonal function may develop following a
      cerebellar infarct, in part, to adapt to the resultant impairment. The present
      study investigated changes in excitability in ipsilateral and contralateral upper
      limb peripheral motor axons in patients with acute cerebellar infarct to
      determine whether plastic changes may have functional relevance. Peripheral nerve
      excitability studies and detailed clinical assessments of functional impairment
      were undertaken in 13 patients with acute unilateral cerebellar infarct within 1
      week of ictus. Changes were followed longitudinally over 1 year at 3, 6 and 12
      months with results compared to 15 age-matched control subjects. Immediately
      following stroke, there were significant alterations in peripheral nerve
      excitability parameters in the upper limbs of patients compared to controls that
      were most evident in the more severely impaired group. There were significant
      correlations between excitability indices and functional scores in the entire
      cohort that demonstrated greater changes in axonal function associated with more
      impairment. Peripheral excitability trended towards normal over the study period
      in the context of clinical improvement. Following an acute cerebellar infarct,
      changes were observed in peripheral motor axons bilaterally that were more
      pronounced in patients with severe functional impairment. The peripheral changes
      may represent a functionally relevant plastic process reflecting altered activity
      to adapt to the disability of the stroke.

PMID- 24939153
TI  - Pei Hsien Tang, MD.

PMID- 24939154
TI  - Establishing technical performance norms for general surgery residents.
AB  - BACKGROUND: Surgery residents are required to achieve performance milestones to
      advance in their residency. Level-specific, technical performance norms that
      could be used as milestones, however, do not currently exist. Our aim was to
      develop level-specific, technical performance norms for general surgery residents
      on select simulated tasks across multiple institutions. STUDY DESIGN: An IRB
      approved, prospective, multi-institutional collaborative study with voluntary
      participation of residents was undertaken at the start of the 2011-2012 academic
      year. General surgery residents (PGY I-V) from seven institutions were tested on
      three laparoscopic and five open simulated surgical tasks, and their performance
      was assessed based on task time and errors. Means and standard deviations of
      performance for each resident level were calculated and compared. Residents with
      performance 1 standard deviation below the mean were considered outliers.
      RESULTS: A total of 147 residents were evaluated. Mean resident age was 28 +/- 3
      years; 42 % were female; and they had attended 74 different medical schools.
      Senior residents (PGY III-V) had more clinical and simulator experience than
      junior residents (PGY I-II) (p < 0.001). Resident performance scores
      progressively increased in all tasks reaching a plateau at a lower PGY level for
      open tasks. Depending on the task, 0-18 % of residents were outliers. When
      surveyed, 66 % of residents agreed that national performance norms for residents
      should exist. CONCLUSIONS: Performance norms were established for select tasks in
      a representative sample of US surgery residents. Such performance norms allow a
      more informed assessment of resident skill through comparison to national data
      and enable the identification of outliers who may benefit from additional
      training.

PMID- 24939155
TI  - SAGES guidelines for the introduction of new technology and techniques.

PMID- 24939156
TI  - Intramucosal carcinoma of the rectum can be safely treated with transanal
      endoscopic microsurgery; clinical support of the revised Vienna classification.
AB  - AIM: The revised Vienna criteria were proposed for classifying rectal neoplasia
      and subsequent treatment strategies. Restaging intramucosal carcinoma to a non
      invasive subgroup seems logical, but clinical support is lacking. In this study,
      we investigated whether distinction between intramucosal carcinomas (IMC) and
      rectal adenoma (RA) is of clinical relevance and whether these neoplasms can all
      be similarly and safely treated by transanal endoscopic microsurgery (TEM).
      METHODS: All consecutive patients with IMC and RA, treated with TEM between 1996
      and 2010 in tertiary referral centre for TEM were included. Long-term outcome of
      88 IMC was compared to 356 pure rectal adenomas (RA). Local recurrence (LR) rate
      was the primary endpoint. Risk factors for LR were analysed. RESULTS: LR was
      diagnosed in 7/88 patients (8.0 %) with IMC and in 33/356 patients with primary
      RA (9.3 %; p = 0.700) and LR-free survival did not differ (p = 0.438). Median
      time to recurrence was 10 months (IQR IMC 5-30; RA 6-16). Overall recurrence
      occurred mainly in the first 3 years (38/40; 95 %). None of the LR revealed
      malignancy on pathological evaluation. No differences could be found in
      complication rates (IMC 9 %; RA 13 %; p = 0.34). Metastases did not occur in
      either group. Independent risk factors for LR were irradical margins at final
      histopathology (HR 2.32; 95 % CI 1.17-4.59; p = 0.016) and more proximal tumours
      (HR 0.84; 95 % CI 0.77-0.92; P = <0.001). CONCLUSION: In this study, IMC of the
      rectum and RA have similar recurrence rates. This supports the revised Vienna
      classification. Both entities can be safely treated with TEM.

PMID- 24939157
TI  - Laparoscopic partial splenectomy is safe and effective in patients with focal
      benign splenic lesion.
AB  - BACKGROUND: Traditionally, splenectomy is considered as the treatment for splenic
      lesions. The risk of early and late complications and the awareness of
      immunologic function of spleen have pushed the development of spleen sparing
      techniques. This study aimed to evaluate the safety and feasibility of
      laparoscopic partial splenectomy in selected patients. METHODS: From May 2011 we
      initiated performing laparoscopic partial splenectomy in patients with focal
      benign splenic lesion. The main surgical procedure consisted of four steps: 1.
      Mobilizing the perisplenic ligaments. 2. Ligating and dissecting the vessels
      which supplying the involved spleen. 3. Dissecting the spleen along the
      demarcation. 4. Hemostasis was achieved by bipolar energy device. The
      perioperative data were collected and analyzed. The follow-up including quality
      of life and splenic regrowth was routinely undergone 6 months after surgery.
      RESULTS: From May 2011 to December 2013, laparoscopic partial splenectomy had
      been performed on 11 patients aged from 13 to 57 (mean 33). The indications
      included nonparasitic cyst (n = 6), lymphangioma (n = 3), and hemangioma (n = 2).
      The mean operative time was 148 min (range 110-200 min). The mean estimated blood
      loss was 189 ml (range 100-400 ml). One patient converted to total splenectomy
      because of hemorrhaging. Two patients suffered from postoperative complications:
      the one who converted to total splenectomy suffered from portal vein thrombosis,
      the other one underwent partial splenectomy suffered from fluid collection around
      splenic recess. There was no blood transfusion and postoperative mortality. All
      patients discharged uneventfully. Seven patients finished the follow-up including
      evaluation of CT scan and quality of life 6 month after surgery. The results
      demonstrated all these patients had different degree of splenic regrowth and
      gained a good quality of life. CONCLUSIONS: Laparoscopic partial splenectomy is
      safe and effective in patients with focal benign splenic lesion. Meanwhile, this
      technique potentially retains some splenic function, and confers the benefit of a
      minimal access technique.

PMID- 24939158
TI  - Prevention of bile duct injury: the case for incorporating educational theories
      of expertise.
AB  - BACKGROUND: Over 700,000 laparoscopic cholecystectomies are performed yearly in
      the US. Despite multiple advantages of laparoscopic surgery, the increased rate
      of bile duct injury (BDI) compared to the traditional, open approach to
      cholecystectomy remains problematic. Due to the seriousness of bile duct injury,
      the time has come for an aggressive educational campaign to better train
      laparoscopic surgeons in order to reduce the incidence of this life-threatening
      and expensive complication. METHODS: We performed a literature review of what is
      currently known about the causes of bile duct injury during laparoscopic
      cholecystectomy. Based on these reviews, we identified educational theories of
      expertise that may be relevant in understanding variable rates of BDI between
      surgeons. Finally, we applied educational theories of expertise to the problem of
      BDI in laparoscopic cholecystectomy to propose how to develop and design an
      effective educational approach for the prevention of BDI. RESULTS: Multiple
      studies demonstrate that the primary causes of BDI during laparoscopic
      cholecystectomy are non-technical. Additionally, there exists a learning curve in
      which the rates of BDI are higher in a surgeon's earlier cases compared to later
      cases and that some surgeons perform laparoscopic cholecystectomy with
      significantly fewer injuries than others. Educational theories indicate that
      interventions that optimize novice to expert development require (1) revealing
      expert knowledge to novices and (2) scaffolding the mental habits of expert-like
      learners. CONCLUSIONS: BDI is an appropriate target for the application of
      educational theories of expertise. Designing better educational interventions for
      the prevention of BDI will require uncovering the hidden knowledge of expert
      surgeons and incorporating the processes of reinvestment and progressive problem
      solving that are inherent to expert performance.

PMID- 24939160
TI  - Incisional hernia after laparoscopic colorectal surgery. Is there any factor
      associated?
AB  - BACKGROUND: Laparoscopic approach is related to, among others, educing abdominal
      wall complications such as incisional hernia (IH). However, there are scarce data
      concerning laparoscopic colorectal surgery (LCRS). The aim of this study was to
      evaluate related factors and incidence of IH following this approach. METHODS: A
      retrospective analysis of consecutive patients who underwent colorectal surgery
      with laparoscopic approach in a single center was performed. Patients with a
      minimum follow-up of 6 months, and also converted to open surgery were included.
      Uni- and multi-variate analyses were performed using the following variables:
      age; gender; type of surgery (left, right, total, or segmental colectomy);
      comorbidities [diabetes and chronic pulmonary obstructive disease (COPD)];
      previous surgery; colorectal disease (benign and malignant); operative time;
      surgical site infection (SSI); and body mass index (BMI). Midline incisions
      (right colectomy) and off-midline incisions (left colectomies and rectal
      resections) were also compared. RESULTS: During a period of 12 years, 1051
      laparoscopic colorectal surgeries were performed. The incidence of IH was 6% (n =
      63). Univariate analysis showed that BMI > 30 kg/m(2) [p < 0.01, OR: 2.3 (1.3
      4.7)], SSI [p < 0.01, OR: 6.5 (3.4-12.5)], operative time >180 min [p < 0.01, OR:
      2.1 (1.2-3.6)] and conversion to open surgery (p = 0.01, OR: 2.4 [1.1-5.0]) were
      related to incisional hernias. BMI and SSI have a statistically significant
      relation with the incidence of IH in multivariate analysis (p < 0.01). No
      statistical difference between right and left colectomy was observed (6.6 vs.
      6.4%, respectively). CONCLUSION: The incidence of IH after LCRS seems to be
      acceptable. BMI over 30 kg/m(2) and SSI are strongly associated to this
      complication.

PMID- 24939159
TI  - Minimally invasive colorectal resection is associated with significantly elevated
      levels of plasma matrix metalloproteinase 3 (MMP-3) during the first month after
      surgery which may promote the growth of residual metastases.
AB  - INTRODUCTION: MMP-3, a member of the matrix metalloproteinase (MMP) family, is
      involved in the breakdown of the extracellular matrix in tissue remodeling and
      may also play a role in cancer progression and metastasis. Minimally invasive
      colorectal resection (MICR) may increase plasma MMP-3 levels directly via
      surgical trauma or indirectly due to surgery-associated elevations in TNF-alpha
      and IL1 which are regulators of MMP-3. This study's purpose was to evaluate
      plasma MMP-3 levels during the first month after MICR for colorectal cancer.
      METHODS: Patients enrolled in an IRB approved data/plasma bank who underwent
      elective MICR for CRC. Blood plasma samples had been collected preoperatively, on
      postoperative day (POD) 1, 3 and at varying postoperative time points and were
      stored at -80  degrees C. The late samples (POD 7-41) were bundled into 7 day
      time blocks and considered as single time points. MMP-3 levels were analyzed in
      duplicate via ELISA and the results reported as mean +/- SD. The paired t test
      was used for analysis (significance, p < 0.008 after Bonferroni's correction).
      RESULTS: A total of 73 CRC patients who underwent MICR met the inclusion
      criteria. The mean PreOp MMP-3 level was 14.9 +/- 7.8 ng/ml (n = 73).
      Significantly elevated mean plasma levels were noted on POD 1 (21.4 +/- 14.7
      ng/ml, n = 73, p < 0.0001), POD 3 (37.9 +/- 21.5 ng/ml, n = 72, p < 0.0001), POD
      7-13 (22.0 +/- 13.0 ng/ml, n = 56, p < 0.0001), POD 14-20 (21.9 +/- 10.3 ng/ml, n
      = 20, p = 0.003), and on POD 21-27 (21.9 +/- 11.43 ng/ml, n = 20, p = 0.002) when
      compared to PreOp levels. Plasma levels returned to the PreOp baseline at the POD
      28-41 time point (n = 16, p = 0.07). CONCLUSION: Plasma MMP-3 levels remained
      significantly elevated from baseline for 4 weeks after MICR for CRC. The early
      postoperative increase in MMP-3 levels may be due to the surgery-related acute
      inflammatory response; the elevation noted during weeks 2-3 may be related to
      wound healing. Increased MMP-3 levels may promote metastases or the growth of
      residual cancer.

PMID- 24939161
TI  - An audit of short- and long-term outcomes after laparoscopic removal of common
      bile duct stones in Finland.
AB  - BACKGROUND AND AIM: To audit short- and long-term outcomes after laparoscopic
      common bile duct exploration (LCBDE) and factors influencing the success of the
      laparoscopic treatment. METHODS: From January 1999 to December 2011, 288 patients
      (93 males) underwent a single-stage laparoscopic cholecystectomy combined with
      LCBDE in two Finnish Hospitals. Short-term outcome data were collected
      prospectively. Long-term outcomes were examined retrospectively. The main
      measures of outcome were the success of laparoscopic CBD stone clearance and
      recurrence of CBD stones in the long-term, with 30-day mortality, morbidity, and
      the length of postoperative hospital stay as secondary outcome measures. RESULTS:
      CBD stones were successfully removed by one-stage laparoscopic procedure in 232
      of the 279 patients (83.2%) with verified CBD stones and after conversion to open
      surgery in additional 28 patients (93.2%). Nineteen patients (6.8%) having
      residual stones after surgery were successfully treated with postoperative ERCP.
      On multivariate analysis, the independent factors associated with a failed
      laparoscopic stone clearance were stone size over 7 mm [OR 3.51 (95% CI 1.53
      8.03), p = 0.003], difficult anatomy [OR 18.01 (5.03-64.49), p < 0.001] and
      transcholedochal approach [OR 2.98 (1.37-4.47), p = 0.006]. Laparoscopic stone
      clearance also failed in all 11 patients having impacted stones at the ampulla of
      Vater. Cumulative long-term recurrence rate was 3.6% at 5 years and 6.0 % at 10
      years. Thirty-day mortality was 0.3% and morbidity 12.2%. Postoperative hospital
      stay was median 2 (IQR 1-3) days after transcystic CBD removal and 4 (IQR 3-7)
      days after transcholedochal CBD removal, p < 0.001. CONCLUSION: Our results show
      that one-stage LC combined with LCBDE stone clearance is safe and effective in
      most patients thus reducing the number of additional, potentially dangerous
      endoscopic procedures. Moreover, large or impacted stones are a risk factor for
      failed stone clearance.

PMID- 24939162
TI  - Fundamental Use of Surgical EnergyTM (FUSE): a curriculum on surgical energy
      based devices.

PMID- 24939163
TI  - A population-based analysis of emergent versus elective paraesophageal hernia
      repair using the Nationwide Inpatient Sample.
AB  - BACKGROUND: As the life expectancy in the United States continues to increase,
      more elderly, sometimes frail patients present with sub-acute surgical conditions
      such as a symptomatic paraesophageal hernia (PEH). While the outcomes of PEH
      repair have improved largely due to the proliferation of laparoscopic surgery,
      there is still a defined rate of morbidity and mortality. We sought to
      characterize the outcomes of both elective and emergent PEH repair using a large
      population-based data set. METHODS: The Nationwide Inpatient Sample was queried
      for primary ICD-9 codes associated with PEH repair (years 2006-2008). Outcomes
      were in-hospital mortality and the occurrence of a pre-identified complication.
      Multivariate analysis was performed to determine the risk factors for
      complications and mortality following both elective and emergent PEH repair.
      RESULTS: A total of 8,462 records in the data, representing 41,723 patients in
      the US undergoing PEH repair in the study interval, were identified. Of these
      procedures, 74.2% was elective and 42.4% was laparoscopic. The overall
      complication and mortality rates were 20.8 and 1.1%, respectively. Emergent
      repair was associated with a higher rate of morbidity (33.4 vs. 16.5%, p < 0.001)
      and mortality (3.2 vs. 0.37%, p < 0.001) than elective repair. Emergent repair
      patients were more likely to be male, were older, and more likely to be minority.
      Logistic modeling revealed that younger age, elective case status, and a
      laparoscopic approach were independently associated with a lower probability of
      complications and mortality. CONCLUSIONS: Patients undergoing emergent PEH repair
      in the United States tend to be older, more likely a racial minority, and less
      likely to undergo laparoscopic repair. Elective repair, younger age, and a
      laparoscopic approach are associated with improved outcomes. Considering all of
      the above, we recommend that patients consider elective repair with a surgeon
      experienced in the laparoscopic approach, especially when symptoms related to the
      hernia are present.

PMID- 24939166
TI  - Nutritional supplements: simply a waste of money or poorly targeted?

PMID- 24939165
TI  - Structure characterization and anti-tyrosinase mechanism of polymeric
      proanthocyanidins fractionated from kiwifruit pericarp.
AB  - To provide information on the structure, activity, and structure-activity
      relationship of kiwifruit (Actinidia chinensis) pericarp proanthocyanidins (PAs),
      they were separated into three fractions. These fractions were further identified
      by MALDI-TOF MS and HPLC-ESI-MS methods. Spectra results revealed that they are
      complex mixtures of B-type propelargonidins, procyanidins, procyanidins gallate,
      and prodelphinidins. Enzymatic activity analysis showed that these compounds
      strongly inhibit the activity of tyrosinase, indicating that they are reversible
      and mixed-type inhibitors of the enzyme. The results obtained from fluorescence
      quenching showed PAs inhibit the enzyme activity by interacting with substrate
      and enzyme. This study confirmed that the mean degree of polymerization (mDP) of
      PAs produces a positive effect on their anti-tyrosinase activity. In addition,
      the antioxidant analysis indicated that PAs possess potent antioxidant activity.
      These conclusions mean kiwifruit pericarp PAs may be explored as insecticides,
      food preservatives, and cosmetic additives. 

PMID- 24939164
TI  - Symptomatic and physiologic outcomes one year after peroral esophageal myotomy
      (POEM) for treatment of achalasia.
AB  - BACKGROUND: Peroral esophageal myotomy (POEM) is a new endoscopic operation for
      the treatment of achalasia. Here, we report 1-year physiologic and symptomatic
      outcomes following the procedure. METHODS: POEM patients from a single
      institution series who were more than 1 year removed from surgery were studied.
      Eckardt and GerdQ scores were obtained to assess symptoms. High-resolution
      manometry (HRM), timed barium esophagram (TBE), and upper endoscopy were
      preformed preoperatively and at 1-year follow-up. 24-h pH monitoring was also
      performed at 1 year follow-up. RESULTS: The study population was comprised of 41
      patients who were more than 1 year post-POEM. One (2%) major complication, a
      contained leak at the EGJ requiring re-operation, and 7 (17%) minor complications
      occurred. Mean length of stay was 1.4 days. At mean 15-month follow-up, Eckardt
      scores improved from pre-POEM 7 +/- 2 to post-POEM 1 +/- 2, (scale 0-12, p <
      .001), and 92% of patients achieved treatment success (Eckardt score <4). Two of
      the three treatment failures in the series occurred in the initial three
      patients. 15% of patients had post-POEM symptoms suggestive of gastroesophageal
      reflux (GerdQ >7). On follow-up HRM, esophagogastric junction integrated
      relaxation pressure was decreased significantly (pre-POEM 28 +/- 12 mmHg vs. post
      POEM 11 +/- 4 mmHg, p < .001), and 47% of patients studied had partial recovery
      of peristalsis. On follow-up TBE, barium column heights were decreased compared
      with preoperatively. Postoperative upper endoscopy revealed esophagitis in 59% of
      patients (11 LA Grade A, 2 LA Grade D). However, of the 13 24-h pH monitoring
      studies performed, only four (31%) demonstrated pathologic esophageal acid
      exposure. CONCLUSIONS: In this series, POEM resulted in greater than 90%
      symptomatic treatment success at mean 15-month follow-up. Rates of iatrogenic
      gastroesophageal reflux, as measured both by symptoms and 24-h pH monitoring,
      appeared to be on par with recent studies of patients undergoing laparoscopic
      Heller myotomy and pneumatic dilation.

PMID- 24939167
TI  - Myopic anisometropia: ocular characteristics and aetiological considerations.
AB  - Anisometropia represents a unique example of ocular development, where the two
      eyes of an individual, with an identical genetic background and seemingly subject
      to identical environmental influences, can grow asymmetrically to produce
      significantly different refractive errors. This review provides an overview of
      the research examining myopic anisometropia, the ocular characteristics
      underlying the condition and the potential aetiological factors involved. Various
      mechanical factors are discussed, including corneal structure, intraocular
      pressure and forces generated during near work that may contribute to development
      of anisomyopia. Potential visually guided mechanisms of unequal ocular growth are
      also explored, including the influence of astigmatism, accommodation, higher
      order aberrations and the choroidal response to altered visual experience. The
      association between binocular vision, ocular dominance and asymmetric refraction
      is also considered, along with a review of the genetic contribution to the
      aetiology of myopic anisometropia. Despite a significant amount of research into
      the biomechanical, structural and optical characteristics of anisometropic eyes,
      there is still no unifying theory, which adequately explains how two eyes within
      the same visual system grow to different endpoints. 

PMID- 24939170
TI  - Patients' perceptions of benefits and risks of complete denture therapy.
AB  - PURPOSE: The aim of this study was to assess patients' perceptions of benefits
      and risks concerning complete denture therapy. A secondary objective was to
      assess the influence of clinical and sociodemographic variables on patients'
      perceptions. MATERIALS AND METHODS: The sample was composed of 104 volunteers who
      presented themselves for complete denture treatment at a dental school. The
      average age of the volunteers was 69.2 years (+/-) 9.3. Patient opinions
      concerning the benefits of complete denture therapy were recorded using a
      previously reported questionnaire. The answers were evaluated in three domains:
      (1) benefits (positive perceptions); (2) risks (negative perceptions); and (3)
      consequences of no treatment. RESULTS: The average time of use of the previous
      dentures was 20 years (SD +/-12.9). Risk factors (negative perceptions) received
      lower scores by the patients, while the consequences of no treatment received
      higher scores. No association was found among evaluations of the previous
      dentures and educational level, marital status, and gender; however, patients'
      evaluation about their previous dentures was significantly different depending on
      age (p = 0.001) and previous dentures' time of use (p = 0.038). CONCLUSIONS:
      Patients presented a positive perception of complete denture therapy, and the
      risk factors (negative perceptions) received the lowest scores. Patient
      perception regarding complete denture therapy was not influenced by educational
      level, evaluation of the previous dentures, or marital status.

PMID- 24939172
TI  - Coming to power: women's fake orgasms and best orgasm experiences illuminate the
      failures of (hetero)sex and the pleasures of connection.
AB  - While some literature has explored women's sexual satisfaction and, to a lesser
      degree, women's faking orgasm experiences, little research has examined the
      context and conditions around women's best and most memorable orgasms. This paper
      utilised thematic analysis of qualitative data from a community sample of 20
      women in the USA (mean age = 34 years, SD = 13.35 years) from a wide range of
      racial, socioeconomic, and sexual identity backgrounds to illuminate their
      experiences with fake or pretend orgasms, and with their best orgasms. While
      faking orgasm narratives reflected themes of wanting to reinforce a partner's
      sexual skills, strategically ending sexual interactions, and suppressing feelings
      of abnormality and shame, best orgasm experiences showcased the power of
      interpersonal connection, the joys of masturbation and other non-penile-vaginal
      intercourse behaviours, and the significance of 'transformative embodiment'.
      Implications for the relative failures of (hetero)sex, particularly in the
      context of gendered power imbalances, along with the importance of deconstructing
      the sexually 'functional' or 'dysfunctional' woman are explored.

PMID- 24939171
TI  - Hydrogen sulfide treatment induces angiogenesis after cerebral ischemia.
AB  - Hydrogen sulfide (H2 S) is a potent vasodilator and regulates cardiovascular
      homeostasis. Furthermore, H2 S has a crucial role in ischemia-reperfusion
      injuries, especially of the heart, liver, and kidneys. This study indicates that
      treatment with hydrogen sulfide is able to restore neurological function after
      ischemic stroke by promoting angiogenesis. Treatment with H2 S augments
      angiogenesis in the peri-infarct area, and it significantly improves functional
      outcomes after 2 weeks in a rat MCAO model. H2 S promotes the phosphorylation of
      AKT and ERK and increases the expression of vascular endothelial growth factor
      (VEGF) and angiopoietin-1 (Ang-1). H2 S-treated rats showed more newly
      synthesized endothelial cells in the ischemic lesion (2.31-fold, P < 0.01). H2 S
      treated astrocytes increased VEGF and Ang-1 expression, and the inhibition of
      phosphatidylinositide 3-kinase (PI3K)/AKT signaling by LY294002 significantly
      reduced H2 S-induced VEGF and Ang-1 expression in astrocytes. Finally, H2 S
      stimulated endothelial cell migration (3.92-fold increase in wound healing assay)
      and tube formation (3.69-fold increase, P < 0.001) through PI3K/AKT signaling. In
      conclusion, treatment with H2 S promotes angiogenesis and thereby contributes to
      improvement of functional outcome after cerebral ischemia. Our findings strongly
      suggest that H2 S may be of value in regenerative recovery after stroke.

PMID- 24939173
TI  - A potential role for allostatic load in preeclampsia.
AB  - Preeclampsia is a multisystemic disorder of pregnancy associated with maternal
      and fetal complications as well as later-life cardiovascular disease. Its exact
      cause is not known. We developed a pregnancy-specific multisystem index score of
      physiologic risk and chronic stress, allostatic load (AL), early in pregnancy.
      Our objective was to determine whether AL measured early in pregnancy was
      associated with increased odds of developing preeclampsia. Data were from a
      single-center, prospectively collected database in a 1:2 individual-matched case
      control of women enrolled at <15 weeks gestation. We matched 38 preeclamptic
      cases to 75 uncomplicated, term deliveries on age, parity, and lifetime smoking
      status. AL was determined using 9 measures of cardiovascular, metabolic, and
      inflammatory function. Cases and matched controls were compared using conditional
      logistic regression. We compared the model's association with preeclampsia to
      that of obesity, a well-known risk factor for preeclampsia, by assessing goodness
      of-fit by Akaike information criterion (AIC), where a difference >1-2 suggests
      better fit. Early pregnancy AL was higher in women with preeclampsia (1.25 +/-
      0.68 vs. 0.83 +/- 0.62, p = 0.002); women with higher AL had increasing odds of
      developing preeclampsia (OR 2.91, 95 % CI 1.50-5.65). The difference between AIC
      for AL and obesity was >2 (AIC 74.4 vs. 84.4), indicating AL had a stronger
      association with preeclampsia. Higher allostatic load in early pregnancy is
      associated with increasing odds of preeclampsia. This work supports a possible
      role of multiple maternal systems and chronic stress early in pregnancy in the
      development of preeclampsia.

PMID- 24939174
TI  - Technoeconomic evaluation of bio-based styrene production by engineered
      Escherichia coli.
AB  - Styrene is an important commodity chemical used in polymers and resins, and is
      typically produced from the petrochemical feedstocks benzene and ethylene.
      Styrene has recently been produced biosynthetically for the first time using
      engineered Escherichia coli, and this bio-based route may represent a lower
      energy and renewable alternative to petroleum-derived styrene. However, the
      economics of such an approach has not yet been investigated. Using an early-stage
      technoeconomic evaluation tool, a preliminary economic analysis of bio-based
      styrene from C(6)-sugar feedstock has been conducted. Owing to styrene's limited
      water solubility, it was assumed that the resulting fermentation broth would
      spontaneously form two immiscible liquid phases that could subsequently be
      decanted. Assuming current C(6) sugar prices and industrially achievable
      biokinetic parameter values (e.g., product yield, specific growth rate),
      commercial-scale bio-based styrene has a minimum estimated selling price (MESP)
      of 1.90 USD kg(-1) which is in the range of current styrene prices. A Monte Carlo
      analysis revealed a potentially large (0.45 USD kg(-1)) standard deviation in the
      MESP, while a sensitivity analysis showed feedstock price and overall yield as
      primary drivers of MESP.

PMID- 24939175
TI  - Inactivation of the phosphoglucomutase gene pgm in Paenibacillus polymyxa leads
      to overproduction of fusaricidin.
AB  - Fusaricidin, a lipodepsipeptide isolated from Paenibacillus polymyxa, has high
      antimicrobial activity against fungi and Gram-positive bacteria. Through
      mutagenesis, we obtained two mutant strains, N1U7 and N17U7, which produce 6.2-
      to 7.9-fold more fusaricidin than their parent strain. Causal mutations were
      identified by whole-genome sequencing, and the two strains each contained at
      least eleven point mutations, including four common mutations. A mutation in the
      PPE04441 gene (pgm), encoding an alpha-phosphoglucomutase, was found to be an
      important factor in fusaricidin overproduction by complementation experiments.
      Null mutation of pgm in the parental strain increased fusaricidin production by
      5.2-fold. Increased growth and cell viability in stationary phase, reduced
      exopolysaccharide production, and increased fusA expression were observed in the
      pgm mutant strains, which might be related to fusaricidin overproduction. This is
      the first report revealing that PGM deficiency leads to an overproduction of
      fusaricidin. 

PMID- 24939176
TI  - Definitive radiotherapy for early-stage hypopharyngeal squamous cell carcinoma.
AB  - The present study analyzed the outcomes of patients with early-stage
      hypopharyngeal squamous cell carcinoma (HPSCC) treated with radical radiotherapy
      (RT) or concurrent chemoradiotherapy (CCRT). We retrospectively reviewed the
      clinical records of 33 patients with early-stage HPSCC who underwent RT or CCRT
      between January 1999 and December 2011. Of the 33 patients who were treated, 12
      had Stage I and 21 had Stage II disease. Patients with Stage I were typically
      treated with RT, while patients with Stage II were treated with CCRT (concurrent
      chemotherapy: 5FU, cisplatin or TS-1). The median follow-up period was 81 months,
      ranging from 15 to 155 months. The 5-year overall survival rates, cause specific
      survival rates, locoregional control rates, and progression-free survival rates
      were 58, 75, 56, and 49 %, respectively. Of the 33 patients, 51 % experienced
      second primary malignancies. Esophageal carcinoma occurred in several cases, and
      was diagnosed either during screening after treatment for the second primary
      malignancy or simultaneously with the second primary malignancy. Advanced-stage
      second malignancies significantly influenced the survival of the patients and the
      control rate for HPSCC. Treatment emphasizing the quality of life after treatment
      is needed, if a poor prognosis is expected because of advanced-stage second
      primary malignancy.

PMID- 24939177
TI  - Multidimensional scale of perceived social support in patients with obstructive
      sleep apnea syndrome.
AB  - Social support is a very important aspect of debilitating diseases. Obstructive
      sleep apnea syndrome (OSAS) is a common disabling disease that impairs a
      patient's quality of life and affects a patient's environment. The
      Multidimensional Scale of Perceived Social Support (MSPSS) is used to measure the
      perception of the sufficiency of social support for individuals. The aim of this
      study is to evaluate the relationship of the MSPSS to the Apnea-Hypopnea Index
      (AHI), age and gender in patients with OSAS. In this study, 183 subjects with a
      diagnosis of OSAS were enrolled. Patients were evaluated with the MSPSS in terms
      of age, gender and polysomnography results. According to the results of this
      study, the MSPSS has found to be higher in men than in women with OSAS and higher
      in moderate-severe OSAS than in mild OSAS. The MSPSS can be an important
      indicator of how patients cope with the disease. 

PMID- 24939179
TI  - Patients should have right to interact with their electronic records, report
      says.

PMID- 24939178
TI  - Regulation of SOD2 and beta-arrestin1 by interleukin-6 contributes to the
      increase of IGF-1R expression in docetaxel resistant prostate cancer cells.
AB  - Although several mechanisms behind resistance to docetaxel in castration
      refractory prostate cancer (CRPC) have been investigated, molecular determinants
      of evolved resistance are still not entirely understood. Proteomics-based
      analysis in this study revealed that SOD2, associated with downregulation of
      reactive oxygen species (ROS), was significantly up-regulated in docetaxel
      resistant (PC3/Doc) cells if compared to sensitive cells, and the expression of
      redox-regulated genes such as IGF-1R, CXCR4, and BCL2 was increased as well.
      Forced expression of SOD2 in sensitive cells led to the increase of IGF-1R and
      association with drug resistance, whereas silencing of SOD2 resulted in the
      decrease of IGF-1R at the protein level in resistant cells. Further study
      revealed that SOD2 acted as a negative regulator of beta-arrestin1 that is an
      important adaptor responsible for degradation of IGF-1R via the changes in ROS,
      as evidenced by observations that an antioxidant agent substantially attenuated
      beta-arrestin1 expression in vitro and in vivo. Finally, we found that blocking
      of IL6 that was up-regulated in resistant cells resulted in attenuation of SOD2
      and STAT3, and simultaneously in increased expression of beta-arrestin1. The
      modulation consequently led to the decreased IGF-1R at both protein and
      transcription levels. Together, our data provide a novel explanation that high
      level of IL6 stimulated SOD2 expression that, at least partially, contributed to
      the low level of ROS that would likely result in a sustained increase in the
      expression of IGF-1R through abolishment of beta-arrestin1 in docetaxel resistant
      cells. 

PMID- 24939180
TI  - Balancing incentives and professionalism in health care payment reform.

PMID- 24939181
TI  - Cancer clinical research: return on investment in the era of value-based
      purchasing.

PMID- 24939182
TI  - The genetics of immunity.
AB  - In this commentary, Brian P. Lazzaro and David S. Schneider examine the topic of
      the Genetics of Immunity as explored in this month's issues of GENETICS and G3:
      Genes|Genomes|Genetics. These inaugural articles are part of a joint Genetics of
      Immunity collection (ongoing) in the GSA journals. 

PMID- 24939183
TI  - The genetics of sex: exploring differences.
AB  - In this commentary, Michelle Arbeitman et al., examine the topic of the Genetics
      of Sex as explored in this month's issues of GENETICS and G3:
      Genes|Genomes|Genetics. These inaugural articles are part of a joint Genetics of
      Sex collection (ongoing) in the GSA journals. 

PMID- 24939184
TI  - Self-incompatibility in Brassicaceae: identification and characterization of SRK
      like sequences linked to the S-locus in the tribe Biscutelleae.
AB  - Self-incompatibility (SI) is a genetic system that prevents self-fertilization in
      many Angiosperms. Although plants from the Brassicaceae family present an
      apparently unique SI system that is ancestral to the family, investigations at
      the S-locus responsible for SI have been mostly limited to two distinct lineages
      (Brassica and Arabidopsis-Capsella, respectively). Here, we investigated SI in a
      third deep-branching lineage of Brassicaceae: the tribe Biscutelleae. By coupling
      sequencing of the SI gene responsible for pollen recognition (SRK) with
      phenotypic analyses based on controlled pollinations, we identified 20 SRK-like
      sequences functionally linked to 13 S-haplotypes in 21 individuals of Biscutella
      neustriaca and 220 seedlings. We found two genetic and phylogenetic features of
      SI in Biscutelleae that depart from patterns observed in the reference
      Arabidopsis clade: (1) SRK-like sequences cluster into two main phylogenetic
      lineages interspersed within the many SRK lineages of Arabidopsis; and (2) some
      SRK-like sequences are transmitted by linked pairs, suggesting local duplication
      within the S-locus. Strikingly, these features also were observed in the Brassica
      clade but probably evolved independently, as the two main SRK clusters in
      Biscutella are distinct from those in Brassica. In the light of our results and
      of what has been previously observed in other Brassicaceae, we discuss the
      ecological and evolutionary implications on SI plant populations of the high
      diversity and the complex dominance relationships we found at the S-locus in
      Biscutelleae.

PMID- 24939185
TI  - Transcriptomes and proteomes define gene expression progression in pre-meiotic
      maize anthers.
AB  - Plants lack a germ line; consequently, during reproduction adult somatic cells
      within flowers must switch from mitotic proliferation to meiosis. In maize (Zea
      mays L.) anthers, hypoxic conditions in the developing tassel trigger pre-meiotic
      competence in the column of pluripotent progenitor cells in the center of anther
      lobes, and within 24 hr these newly specified germinal cells have patterned their
      surrounding neighbors to differentiate as the first somatic niche cells.
      Transcriptomes were analyzed by microarray hybridization in carefully staged
      whole anthers during initial specification events, after the separation of
      germinal and somatic lineages, during the subsequent rapid mitotic proliferation
      phase, and during final pre-meiotic germinal and somatic cell differentiation.
      Maize anthers exhibit a highly complex transcriptome constituting nearly three
      quarters of annotated maize genes, and expression patterns are dynamic. Laser
      microdissection was applied to begin assigning transcripts to tissue and cell
      types and for comparison to transcriptomes of mutants defective in cell fate
      specification. Whole anther proteomes were analyzed at three developmental stages
      by mass spectrometric peptide sequencing using size-fractionated proteins to
      evaluate the timing of protein accumulation relative to transcript abundance. New
      insights include early and sustained expression of meiosis-associated genes
      (77.5% of well-annotated meiosis genes are constitutively active in 0.15 mm
      anthers), an extremely large change in transcript abundances and types a few days
      before meiosis (including a class of 1340 transcripts absent specifically at 0.4
      mm), and the relative disparity between transcript abundance and protein
      abundance at any one developmental stage (based on 1303 protein-to-transcript
      comparisons). 

PMID- 24939187
TI  - Bacterial methionine biosynthesis.
AB  - Methionine is essential in all organisms, as it is both a proteinogenic amino
      acid and a component of the cofactor, S-adenosyl methionine. The metabolic
      pathway for its biosynthesis has been extensively characterized in Escherichia
      coli; however, it is becoming apparent that most bacterial species do not use the
      E. coli pathway. Instead, studies on other organisms and genome sequencing data
      are uncovering significant diversity in the enzymes and metabolic intermediates
      that are used for methionine biosynthesis. This review summarizes the different
      biochemical strategies that are employed in the three key steps for methionine
      biosynthesis from homoserine (i.e. acylation, sulfurylation and methylation). A
      survey is presented of the presence and absence of the various biosynthetic
      enzymes in 1593 representative bacterial species, shedding light on the non
      canonical nature of the E. coli pathway. This review also highlights ways in
      which knowledge of methionine biosynthesis can be utilized for biotechnological
      applications. Finally, gaps in the current understanding of bacterial methionine
      biosynthesis are noted. For example, the paper discusses the presence of one gene
      (metC) in a large number of species that appear to lack the gene encoding the
      enzyme for the preceding step in the pathway (metB), as it is understood in E.
      coli. Therefore, this review aims to move the focus away from E. coli, to better
      reflect the true diversity of bacterial pathways for methionine biosynthesis. 

PMID- 24939186
TI  - Sex-determination system in the diploid yeast Zygosaccharomyces sapae.
AB  - Sexual reproduction and breeding systems are driving forces for genetic
      diversity. The mating-type (MAT) locus represents a mutation and chromosome
      rearrangement hotspot in yeasts. Zygosaccharomyces rouxii complex yeasts are
      naturally faced with hostile low water activity (aw) environments and are
      characterized by gene copy number variation, genome instability, and
      aneuploidy/allodiploidy. Here, we investigated sex-determination system in
      Zygosaccharomyces sapae diploid strain ABT301(T), a member of the Z. rouxii
      complex. We cloned three divergent mating type-like (MTL) alpha-idiomorph
      sequences and designated them as ZsMTLalpha copies 1, 2, and 3. They encode
      homologs of Z. rouxii CBS 732(T) MATalpha2 (amino acid sequence identities
      spanning from 67.0 to 99.5%) and MATalpha1 (identity range 81.5-99.5%). ABT301(T)
      possesses two divergent HO genes encoding distinct endonucleases 100% and 92.3%
      identical to Z. rouxii HO. Cloning of MATA: -idiomorph resulted in a single
      ZsMTLA: locus encoding two Z. rouxii-like proteins MATA: 1 and MATA: 2. To assign
      the cloned ZsMTLalpha and ZsMTLA: idiomorphs as MAT, HML, and HMR cassettes, we
      analyzed their flanking regions. Three ZsMTLalpha loci exhibited the DIC1-MAT
      SLA2 gene order canonical for MAT expression loci. Furthermore, four putative HML
      cassettes were identified, two containing the ZsMTLalpha copy 1 and the remaining
      harboring ZsMTLalpha copies 2 and 3. Finally, the ZsMTLA: locus was 3'-flanked by
      SLA2, suggesting the status of MAT expression locus. In conclusion, Z. sapae
      ABT301(T) displays an aalphaalphaalpha genotype missing of the HMR silent
      cassette. Our results demonstrated that mating-type switching is a hypermutagenic
      process in Z. rouxii complex that generates genetic diversity de novo. This error
      prone mechanism could be suitable to generate progenies more rapidly adaptable to
      hostile environments. 

PMID- 24939189
TI  - Isolated superficial peroneal neuropathy: a rare presentation of Hansen's disease
      (leprosy).

PMID- 24939188
TI  - The rising prevalence of self-reported hypertension among Chinese subjects: a
      population-based study from 121 895 household interviews.
AB  - BACKGROUND: Hypertension is one of the most important public health issues
      worldwide. AIM: We assessed the prevalence rates of self-reported hypertension in
      Hong Kong between 2001 and 2008 and evaluated factors associated with its
      prevalence. DESIGN: Serial cross-sectional surveys. METHODS: Territory-wide
      Household surveys in the Hong Kong population in the years 2001, 2002, 2005 and
      2008 were included. Population-adjusted prevalence of self-reported hypertension
      were compared across calendar years. The independent association of these
      variables with hypertension was evaluated by multivariate regression analysis
      with self-reported hypertension as a binary outcome. RESULTS: There were 121 895
      subjects interviewed, among which 103 367 were adults aged >=15 years. The age-
      and gender-adjusted prevalence of self-reported hypertension in 2001, 2002, 2005
      and 2008 among male adults was 4.73, 6.68, 7.96 and 9.82%, respectively, and
      among female adults, the prevalence was 6.13, 8.28, 10.00 and 11.58%,
      respectively. Advanced age (adjusted odds ratios [AOR]: 47.1, 95% CI 33.6-66.0
      for the age group 40-65 years; AOR 256.2, 95% CI 182.4-360.0 for the age group 66
      100 years; referent 0-39 years), female gender (AOR 0.81, 95% CI 0.74-0.88 for
      male) and a low median household income (AOR 1.56, 95% CI 1.31-1.85 for income <=
      US$1289; referent >= US$6444) were significantly associated with hypertension
      (all P < 0.001). CONCLUSIONS: This is the first study to show differences between
      socioeconomic groups in this Chinese population with higher rates among women and
      the less affluent. Similarly, it is the first to show gender differences with
      higher rates among women.

PMID- 24939190
TI  - Diagnostic value of MUC1 and EpCAM mRNA as tumor markers in differentiating
      benign from malignant pleural effusion.
AB  - BACKGROUND: The sensitivity of conventional cytology for the detection of tumor
      cells in pleural effusion (PE) is inadequate. Mucine 1 (MUC1) and epithelial cell
      adhesion molecule (EpCAM) are two frequently and intensely expressed tumor
      associated antigens in malignancies of epithelial origin. OBJECTIVE: To evaluate
      the diagnostic value of pleural fluid MUC1 and EpCAM mRNA in differentiating
      benign and malignant PE. METHOD: Fifty-eight patients with malignant PE and 40
      patients with benign PE were included in this study. Pleural fluid MUC1 and EpCAM
      mRNA levels were measured by quantitative real-time PCR. Carcinoembryonic antigen
      (CEA) and cytokeratin 19 fragment (Cyfra21-1) were also detected simultaneously.
      The receiver operating characteristic (ROC) curves were constructed to assess
      diagnostic performance of the four tumor markers in PE. RESULTS: For the
      diagnosis of malignant PE, MUC1 and EpCAM mRNA had larger area under ROC curves
      (0.916 and 0.922) and higher sensitivity (67.2 and 70.7%) with the same
      specificity, when compared with CEA and Cyfra21-1 (0.821 and 0.780; 48.3 and
      44.8%, respectively). By combining cytology with MUC and EpCAM, a positive result
      indicating the presence of malignancy was achieved in 87.9%, with a good
      specificity of 95%. CONCLUSIONS: Compared with CEA and Cyfra21-1, the performance
      of MUC1 and EpCAM mRNA in malignant PE diagnosis was better. MUC1 and EpCAM mRNA
      in combination with cytology is a highly sensitive and specific diagnostic tool
      for detecting malignancy in PE.

PMID- 24939191
TI  - Taurolidine-citrate-heparin catheter lock solution reduces staphylococcal
      bacteraemia rates in haemodialysis patients.
AB  - BACKGROUND: Infection is second only to cardiovascular disease as a cause of
      death in the haemodialysis (HD) population. AIM: : To assess the effect of
      introducing catheter lock solution taurolidine-citrate-heparin to all tunnelled
      central venous catheters (TCVCs) on staphylococcal bloodstream infection rates in
      patients on chronic HD. DESIGN: Observational, prospective analysis of the
      incidence rates of staphylococcal bacteraemic events in National Health Service
      (NHS) Greater Glasgow & Clyde and NHS Forth Valley between April 2011 and June
      2013, with taurolidine-citrate-heparin catheter lock solution introduced July
      2012. METHODS: Data were collected each calendar quarter through a structured
      query language interrogation of the renal unit electronic patient record, with
      staphylococcal bacteraemic events expressed per 1000 vascular access exposed
      days. Comparison between pre- and post-intervention periods was made by student's
      t-testing. RESULTS: Two hundred and thirty-nine staphylococcal bacteraemic events
      occurred over a total of 424,835 HD days in 565 patients; 81 events in 289,389
      arterio-venous fistula or graft (AVF/AVG) HD days and 158 events in 135 446 TCVC
      HD days. Following the introduction of taurolidine-citrate-heparin, bacteraemic
      events in patients dialysing via a TCVC fell from 1.59/1000 HD days to 0.69/1000
      HD days, P = 0.004. The staphylococcal bacteraemia rate in AVF/AVGs remained
      unchanged; 0.30 vs. 0.26/1000 HD days, P = 0.52. CONCLUSIONS: Replacing heparin
      5000 IU with Taurolidine-citrate-heparin as catheter lock solution was associated
      with a statistically significant 56% reduction in staphylococcal bloodstream
      infection rates in our TCVC HD population.

PMID- 24939192
TI  - PET radioligands for in vivo visualization of neuroinflammation.
AB  - Neuroinflammation is a well-orchestrated, dynamic, multicellular process playing
      a major role in neurodegenerative disorders. The microglia which make up the
      innate immune system of the central nervous system are key cellular mediators of
      neuroinflammatory processes. In normal condition they exert a protective
      function, providing tissue repair by releasing anti-inflammatory cytokines and
      neurotrophic factors. Upon neuronal injury or infection, they become
      overactivated, thereby releasing neurotoxic substances, amplifying
      neuroinflammation leading to neurodegeneration. Positron emission tomography
      (PET) provides a sensitive non-invasive imaging technique to study and quantify
      receptor and enzyme expression. A radiolabeled tracer for a protein
      (over)expressed in neuroinflammation and more specifically for the overactivated
      microglia would be useful as a diagnostic tool in the follow-up of
      neuroinflammation progression and to study the efficacy of anti-inflammatory
      therapy over time. In this manuscript, an overview of potential PET tracer
      targets upregulated during neuroinflammation is provided together with the
      current radiotracers used to image these targets. In addition, lead structures to
      develop radiotracers for new targets are suggested. 

PMID- 24939194
TI  - What's old is new.

PMID- 24939196
TI  - Reasons for initial formula supplementation of healthy breastfeeding newborns.
AB  - In a retrospective review of 302 hospital charts, 38 percent of newborns whose
      mothers planned to exclusively breastfeed received formula before hospital
      discharge. Those breastfeeding infants who did not receive formula were
      significantly younger at first breastfeeding than infants who received formula.
      Significantly more infants born by cesarean (51 percent) received supplementation
      than those born vaginally (31 percent). Birth between 9 p.m. and 10 a.m. and a
      hospital stay for more than 24 hours increased odds of supplementation. Nurses
      can explore barriers to exclusive breastfeeding unique to their hospitals to
      develop strategies that facilitate breastfeeding support and decrease formula
      supplementation. 

PMID- 24939193
TI  - 'RetinoGenetics': a comprehensive mutation database for genes related to
      inherited retinal degeneration.
AB  - Inherited retinal degeneration (IRD), a leading cause of human blindness
      worldwide, is exceptionally heterogeneous with clinical heterogeneity and genetic
      variety. During the past decades, tremendous efforts have been made to explore
      the complex heterogeneity, and massive mutations have been identified in
      different genes underlying IRD with the significant advancement of sequencing
      technology. In this study, we developed a comprehensive database,
      'RetinoGenetics', which contains informative knowledge about all known IRD
      related genes and mutations for IRD. 'RetinoGenetics' currently contains 4270
      mutations in 186 genes, with detailed information associated with 164 phenotypes
      from 934 publications and various types of functional annotations. Then extensive
      annotations were performed to each gene using various resources, including Gene
      Ontology, KEGG pathways, protein-protein interaction, mutational annotations and
      gene-disease network. Furthermore, by using the search functions, convenient
      browsing ways and intuitive graphical displays, 'RetinoGenetics' could serve as a
      valuable resource for unveiling the genetic basis of IRD. Taken together,
      'RetinoGenetics' is an integrative, informative and updatable resource for IRD
      related genetic predispositions. Database URL: http://www.retinogenetics.org/. 

PMID- 24939197
TI  - A cocooning project to protect newborns from pertussis.
AB  - The Pertussis Cocooning Project was created through a collaborative effort by a
      health care organization and a State Department for Public Health to decrease
      community pertussis rates and protect infants from the deadly effects of
      pertussis. Free pertussis immunizations are provided to all mothers who give
      birth at the health care organization and to all infants' family members and
      caregivers older than 18 years. 

PMID- 24939198
TI  - Developing a hand-held Pap test card to improve cervical cancer screening.
AB  - We identified an educational deficit among clients at a community health clinic
      regarding the latest cervical cancer screening recommendations. A literature
      search on Pap testing and problems with compliance or screening indicated
      multiple barriers to cervical cancer screening. Education, health promotion and
      the use of a hand-held health card/record were identified as methods to educate
      women regarding cervical cancer prevention. We developed a hand-held Pap test
      card to be similar to an immunization card. The card was designed to fulfill the
      needs of both clients and practitioners. 

PMID- 24939199
TI  - Implications of psychoactive 'bath salts' use during pregnancy.
AB  - Psychoactive bath salts (PABS) comprise a group of highly dangerous designer
      drugs showing a sharp escalation in reported U.S. exposures from 2010 through
      2012, following rapid spread of the drug in Europe. Since a federal ban on the
      major ingredients in October 2011, numbers have declined. However, evidence from
      the United Kingdom shows an initial decline after the UK ban in 2010 with a 400
      percent increase in reports by 2012. Actual information about the effect of PABS
      use on pregnant women and fetuses is almost nonexistent. Clinicians should be
      aware of the potential maternal, fetal and neonatal effects of PABS. 

PMID- 24939200
TI  - The role of the nurse-physician leadership dyad in implementing the Baby-Friendly
      Hospital Initiative.
AB  - The concept of the nurse-physician leadership dyad incorporates the expertise of
      both nurses and physicians as leaders of change within health system
      environments. The leadership dyad model has been used traditionally in health
      care administrative settings to manage utilization of resources more effectively.
      Because the Baby-Friendly designation requires major cultural shifts in long
      standing maternity care practices, an interdisciplinary approach to
      implementation is necessary. 

PMID- 24939201
TI  - Treatment of dyspareunia secondary to vulvovaginal atrophy.
AB  - Declining estrogen levels associated with menopause can result in vulvovaginal
      atrophy and some degree of dyspareunia for more than half of all women in
      menopause. In 2013, the U.S. Food and Drug Administration approved ospemifene, a
      nonhormonal oral medication for the treatment of dyspareunia in menopause. This
      article will provide an overview of ospemifene and its indications, side effects
      and implications for nurses. 

PMID- 24939203
TI  - Examining nurses' work environments to improve safety.

PMID- 24939202
TI  - Clinical indications associated with primary cesarean birth.
AB  - Cesarean birth is the most common surgical procedure in the United States and is
      associated with increased morbidity and mortality when compared to vaginal birth.
      Of the more than 4 million births a year, one in three is now a cesarean. A
      better understanding of the clinical indications contributing to the current
      prevalence in primary cesarean rates can inform prevention strategies. This
      column takes a second look at two recent studies in which researchers evaluated
      the clinical indications associated with primary cesarean birth rates. 

PMID- 24939205
TI  - A nurse's sixth sense.

PMID- 24939206
TI  - Understanding the views of those who care for patients with cancer on advance
      care planning and end-of-life care.
AB  - An electronic survey was used to assess the views of a diverse nationwide cohort
      of health care professionals regarding advance care planning and end-of-life
      care. A total of 645 responses were received. If diagnosed with a serious
      incurable illness with limited life expectancy, 97% would want to discuss their
      prognosis, 74% would refuse cardiopulmonary resuscitation, and 72% favored
      supportive/comfort care to more aggressive life-prolonging treatments. However,
      prognosis was thought to be discussed with only 52% of such patients, and just 5%
      thought doctors were either very or extremely successful at explaining advanced
      life-sustaining treatments to patients. Greater than 90% believed these
      discussions should best occur when a patient is thought to have one or more years
      to live and 80% thought they are best initiated in the outpatient setting. 

PMID- 24939207
TI  - Attitudes Toward and Experiences in End-of-life Care Education in the Intensive
      Care Unit: A Survey of Resident Physicians.
AB  - INTRODUCTION: Resident physicians provide the most physician care to intensive
      care unit (ICU) patients. The body of literature about residents' palliative and
      end-of-life care (PC/EOLC) experiences in the ICU is limited. To our knowledge,
      this is the first study to assess resident physicians in multiple specialties
      regarding PC/EOLC in the ICU. METHODS: A Web-based survey was developed and
      administered to all resident physicians in a single academic institution who had
      completed at least 1 dedicated ICU rotation. RESULTS: Residents reported moderate
      comfort in dealing with end-of-life (EOL) issues and felt somewhat prepared to
      care for critically ill patients at the EOL. Feedback should be provided to
      residents regarding their PC/EOLC skills, and education should be tailored to
      residents rotating in the ICU.

PMID- 24939208
TI  - Prior Study of Cross-Cultural Validation of McGill Quality-of-Life Questionnaire
      in Mainland Mandarin Chinese Patients With Cancer.
AB  - The validation of McGill quality-of-life questionnaire (MQOLQ) in mainland China,
      which had already been used in multicultural palliative care background including
      Hong Kong and Taiwan, remained unknown. Eligible patients completed the
      translated Chinese version of McGill questionnaires (MQOL-C), which had been
      examined before the study. Construct validity was preliminarily assessed through
      exploratory factor analysis extracting 4 factors that construct a new hypothesis
      model and then the original model was proved to be better confirmed by
      confirmatory factor analysis. Internal consistency of all the subscales was
      within 0.582 to 0.917. Furthermore, test-retest reliability ranged from 0.509 to
      0.859, which was determined by Spearman rank correlation coefficient. Face
      validation and feasibility also confirm the good validity of MQOL-C. The MQOL-C
      has satisfied validation in mainland Chinese patients with cancer, although
      cultural difference should be considered while using it. 

PMID- 24939209
TI  - Wishes of Patients With Terminal Cancer and Influencing Factors Toward the Use of
      Antibiotics in Taiwan.
AB  - CONTEXT: The use of antibiotics is a common ethical dilemma in palliative care,
      thus identifying the concerns of patients with terminal cancer and respecting
      their wishes are important in making an ethically justified decision. OBJECTIVES:
      The aim of this study was to understand wishes of patients with terminal cancer
      and determine influencing factors toward the use of antibiotics. METHODS: Two
      hundred and one patients with terminal cancer, admitted to a palliative care unit
      in Taiwan, completed a structured questionnaire interview, including demographic
      characteristics, knowledge and attitudes on antibiotics, the health locus of
      control, subjective norms, and the wishes to use antibiotics. RESULTS: The most
      common misconception was "Antibiotics use is helpful to all terminal patients
      with infection," which only 13.4% respondents disagreed. Of the 201patients, 92
      (45.8%) expressed their wishes to use antibiotics even in the very terminal
      stage, and around one-fourth (26.4%) of patients wished not to use antibiotics,
      the remaining 27.8% were unclear. The most influential persons were medical
      professionals. The results of logistic regression analysis that showed
      familiarity with antibiotics, subjective norms, and the attitude toward burdens
      of antibiotics were the most significant predicting variables for those wishing
      to use antibiotics (odds ratio [OR] = 4.133, 95% confidence interval [CI] = 1.012
      16.880; OR = 1.890, 95% CI = 1.077-3.317; and OR = 1.255, 95% CI = 1.047-1.503).
      CONCLUSION: This study indicated the responsibility of medical professionals to
      convey burdens of using antibiotics to patients and family. Otherwise, by
      enhancing professional training and performing effective communication with
      patients, we can reach a more appropriate decision in the use of antibiotics.

PMID- 24939211
TI  - Tailoring the properties of quadruplex nucleobases for biological and
      nanomaterial applications.
AB  - Guanine DNA quadruplexes are interesting and important biological objects because
      they represent potential targets for regulatory drugs. Their use as building
      blocks for biomaterial applications is also being investigated. This contribution
      reports the in silico design of artificial building blocks derived from xanthine.
      Methods of quantum chemistry were used to evaluate the properties of xanthine
      structures relative to those containing guanine, the natural reference used.
      Tailoring the xanthine core showed that the base stacking and the ion
      coordination were significantly enhanced in the designed systems, while the ion
      transport properties were not affected. Our study suggests that the 9-deaza-8
      haloxanthine bases (where the halogen is fluorine or chlorine) are highly
      promising candidates for the development of artificial quadruplexes and
      quadruplex-active ligands. 

PMID- 24939210
TI  - Musculoskeletal pain in Arctic indigenous and non-indigenous adolescents,
      prevalence and associations with psychosocial factors: a population-based study.
AB  - BACKGROUND: Pain is common in otherwise healthy adolescents. In recent years
      widespread musculoskeletal pain, in contrast to single site pain, and associating
      factors has been emphasized. Musculoskeletal pain has not been examined in Arctic
      indigenous adolescents. The aim of this study was to explore the prevalence of
      widespread musculoskeletal pain and its association with psychosocial factors,
      with emphasis on gender- and ethnic differences (Sami vs. non-Sami), and the
      influence of pain related functional impairment. METHODS: This is a cross
      sectional study based on The Norwegian Arctic Adolescent Health Study; a school
      based survey responded by 4,881 10th grade students (RR: 83%) in North Norway, in
      2003-2005. 10% were indigenous Sami. Musculoskeletal pain was based on reported
      pain in the head, shoulder/neck, back and/or arm/knee/leg, measured by the number
      of pain sites. Linear multiple regression was used for the multivariable
      analyses. RESULTS: The prevalence of musculoskeletal pain was high, and
      significantly higher in females. In total, 22.4% reported 3-4 pain sites. We
      found a strong association between musculoskeletal pain sites and psychosocial
      problems, with a higher explained variance in those reporting pain related
      functional impairment and in females. There were no major differences in the
      prevalence of musculoskeletal pain in Sami and non-Sami, however the associating
      factors differed somewhat between the indigenous and non-indigenous group. The
      final multivariable model, for the total sample, explained 21.2% of the variance
      of musculoskeletal pain. Anxiety/depression symptoms was the dominant factor
      associated with musculoskeletal pain followed by negative life events and school
      related stress. CONCLUSIONS: Anxiety/depression, negative life events, and school
      related stress were the most important factors associated with musculoskeletal
      pain, especially in those reporting pain related functional impairment. The most
      important sociocultural aspect is the finding that the indigenous Sami are not
      worse off.

PMID- 24939212
TI  - Phase II trial of vatalanib in patients with advanced or metastatic pancreatic
      adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001).
AB  - PURPOSE: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor
      with strong affinity for platelet-derived growth factor and vascular endothelial
      growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter
      therapeutic trial investigating the efficacy and tolerability of vatalanib in
      patients with metastatic or advanced pancreatic cancer who failed first-line
      gemcitabine-based therapy. METHODS: Vatalanib treatment consisted of a twice
      daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during
      week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The
      primary objective of this study was to evaluate the 6-month survival rate.
      RESULTS: Sixty-seven patients were enrolled. The median age was 64, and 66% (N =
      43) had only one prior regimen. Common grade 3/4 adverse events included
      hypertension (20%; N = 13), fatigue (17%; N = 11), abdominal pain (17%; N = 11),
      and elevated alkaline phosphatase (15%; N = 10). Among the 65 evaluable patients,
      the 6-month survival rate was 29% (95% CI 18-41%) and the median progression-free
      survival was 2 months. Fifteen patients survived 6 months or more. Two patients
      had objective partial responses, and 28% of patients had stable disease. Changes
      in biomarkers including soluble VEGF and vascular endothelial growth factor
      receptor did not correlate with response to drug. CONCLUSION: Vatalanib was well
      tolerated as a second-line therapy and resulted in favorable 6-month survival
      rate in patients with metastatic pancreatic cancer, compared with historic
      controls.

PMID- 24939213
TI  - Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted
      antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer:
      clinical implications of the effect of covariates.
AB  - PURPOSE: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprising
      the humanized monoclonal antibody trastuzumab linked to DM1, a highly potent
      cytotoxic agent. A population pharmacokinetic (PK) analysis was performed to
      estimate typical values and interindividual variability of T-DM1 PK parameters
      and the effects of clinically relevant covariates. METHODS: Serum samples were
      collected from 671 patients with human epidermal growth factor receptor 2
      positive locally advanced or metastatic breast cancer (MBC) who received single
      agent T-DM1 in five phase I to phase III studies. Nonlinear mixed-effects
      modeling with the first-order conditional estimation method was used. RESULTS: A
      linear two-compartment model with first-order elimination from the central
      compartment described T-DM1 PKs in the clinical dose range. T-DM1 elimination
      clearance was 0.676 L/day, volume of distribution in the central compartment (V
      c) was 3.127 L, and terminal elimination half-life was 3.94 days. Age, race,
      region, and renal function did not influence T-DM1 PK. Given the low-to-moderate
      effect of all statistically significant covariates on T-DM1 exposure, none of
      these covariates is expected to result in a clinically meaningful change in T-DM1
      exposure. CONCLUSIONS: T-DM1 PK properties are consistent and predictable in
      patients. A further refinement of dose based on baseline covariates other than
      body weight for the current 3.6 mg/kg regimen would not yield clinically
      meaningful reductions in interindividual PK variability in patients with MBC.

PMID- 24939214
TI  - Hypothyroidism as a potential biomarker of efficacy of famitinib, a novel VEGFR-2
      inhibitor in metastatic breast cancer.
AB  - PURPOSE: Hypothyroidism is a common adverse event in patients treated with anti
      VEGFR-2 targeting agents and may be a valuable predictive factor of efficacy.
      Famitinib is an inhibitor of multiple tyrosine kinases mainly targeting VEGFR-2.
      The objectives of this study were to assess the efficacy and safety of famitinib
      in patients with pretreated HER2-negative metastatic breast cancer (MBC) and to
      explore potential of famitinib-induced hypothyroidism and serum vascular
      endothelial growth factor (VEGF) level for efficacy prediction. MATERIALS AND
      METHODS: The primary end point was objective response rate (ORR). Famitinib was
      administered 25 mg/d. Thyroid function assessments were done at baseline and then
      every 4 weeks. Plasma levels of VEGF were determined at baseline and 2 cycles
      after treatment. RESULTS: A total of 28 patients were enrolled. ORR was 14.3%.
      The most common grade 3/4 AEs were hand-foot syndrome (25.0%), proteinuria
      (21.4%) and hypertension (17.9%). 64.0% patients were observed with elevated
      thyroid-stimulating hormone (TSH) (>4.94 mIU/L) at any time during the entire
      treatment period. Sixteen patients with an elevated TSH had a significantly
      longer PFS than nine patients with no TSH elevation (107 vs. 53 days,
      respectively, P = 0.002). TSH elevation was also an independent predictor of PFS
      in a Cox regression model. Plasma VEGF levels did not correlate significantly
      with clinical outcomes. CONCLUSIONS: Famitinib did show substantial anti-tumor
      activities with a good safety profile in heavily pretreated patients with HER2
      negative MBC. Famitinib-related TSH increase may be an early indicator of its
      efficacy. Serial monitoring of serum TSH may help define VEGFR-2-dependent or
      VEGFR-2-independent drug resistance.

PMID- 24939215
TI  - Tailoring the GVHD prophylaxis regimen according to transplantation associated
      toxicities-Substituting the 3rd dose of methotrexate to mycophenolate mofetil.
AB  - We hypothesized that in patients with early post allogeneic transplantation
      toxicities, the omission of the 3rd dose of methotrexate with concomitant
      starting of MMF would favorably affect complications. We found a higher incidence
      of grade 2-4 acute GVHD in patients given two doses methotrexate and MMF (n=31)
      compared to those given three courses of methotrexate (n=70) (p=.004), while
      grade 3-4 was similar. Other transplantation outcomes, including overall regimen
      related-toxicity, were comparable. We conclude that tailoring the GVHD
      prophylaxis regimen may decrease the early post transplantation complications,
      however this come at the extent of a higher incidence of non-severe acute GVHD. 

PMID- 24939217
TI  - Clinically silent clonal cytogenetic abnormalities arising in patients treated
      for lymphoid neoplasms.
AB  - Newly emerged clonal cytogenetic abnormalities (CCA) in patients with prior
      cytotoxic therapy are highly concerning for therapy-related myeloid neoplasms (t
      MN). In some patients, however, CCA appeared to be clinically "silent". In this
      study, we describe 25 patients who developed CCA after they received cytotoxic
      therapies for lymphoid neoplasms but never developed t-MN. These clinically
      "silent" CCA were always present as single abnormalities, often detected in a
      small subset of cells, and tended to disappear over time. We conclude that the
      occurrence of CCA is not always associated with t-MN. Clinical correlation is
      essential to guide a proper management of these patients. 

PMID- 24939216
TI  - Rapamycin inhibits pre-B acute lymphoblastic leukemia cells by downregulating DNA
      and RNA polymerases.
AB  - Rapamycin has been shown to inhibit the growth of leukemic cells via an unknown
      mechanism. In our current study, we show that rapamycin activates autophagy in
      pediatric t(1;19) pre-B acute lymphoblastic leukemia (pre-B ALL) cells and
      thereby inhibits proliferation and induces growth arrest in these cells.
      Rapamycin was found to downregulate an extensive array of positive cell cycle
      regulators, reduce the total DNA and RNA levels, and specifically downregulate
      the gene transcription of DNA pol delta1 and RNA pol II. Furthermore, we show
      that both rapamycin and starvation caused a downregulation of the DNA pol delta1
      and RNA pol II proteins which was reversed by the autophagy inhibitor 3-MA.
      Consistent with the results of our autophagic flux analysis, confocal microscopy
      indicated that both rapamycin and starvation cause the colocalization of DNA pol
      delta1 and RNA pol II with GFP-LC3 at autophagosomes. This colocalization was
      blocked by the autophagy inhibitor bafilomycin A1 which inhibits the fusion
      between autophagosomes and lysosomes. These data suggest that rapamycin inhibits
      the growth of pediatric t(1;19) pre-B ALL cells through both transcriptional
      inhibition and autophagic degradation of DNA pol delta1 and RNA pol II. 

PMID- 24939218
TI  - Carfilzomib promotes the osteogenic differentiation potential of mesenchymal stem
      cells derived from myeloma patients by inhibiting notch1 activity in vitro.
AB  - Notch1 signaling plays a key role in the differentiation of mesenchymal stem
      cells (MSCs). Carfilzomib (CFZ), a second-generation proteasome inhibitor, has
      potent cytotoxicity against myeloma cells. In this study, we investigated the
      effects of CFZ on the osteogenic differentiation potential of MSCs derived from
      myeloma patients (MM-MSCs) in vitro. MM-MSCs showed decreased osteogenic
      differentiation ability, together with an impairment of notch1 deactivation. The
      notch1 inhibitor DAPT and the downregulation of notch1 by shRNA promoted
      osteogenesis in MM-MSCs. Additionally, CFZ treatment resulted in notch1
      inhibition and enhanced osteogenesis in MM-MSCs. These findings suggest that CFZ
      stimulates osteogenesis via notch1 inhibition. 

PMID- 24939219
TI  - Most patients with atrial fibrillation need anticoagulants, NICE says.

PMID- 24939220
TI  - Stenotrophomonas comparative genomics reveals genes and functions that
      differentiate beneficial and pathogenic bacteria.
AB  - BACKGROUND: In recent years, the number of human infections caused by
      opportunistic pathogens has increased dramatically. Plant rhizospheres are one of
      the most typical natural reservoirs for these pathogens but they also represent a
      great source for beneficial microbes with potential for biotechnological
      applications. However, understanding the natural variation and possible
      differences between pathogens and beneficials is the main challenge in furthering
      these possibilities. The genus Stenotrophomonas contains representatives found to
      be associated with human and plant host. RESULTS: We used comparative genomics as
      well as transcriptomic and physiological approaches to detect significant borders
      between the Stenotrophomonas strains: the multi-drug resistant pathogenic S.
      maltophilia and the plant-associated strains S. maltophilia R551-3 and S.
      rhizophila DSM14405T (both are biocontrol agents). We found an overall high
      degree of sequence similarity between the genomes of all three strains. Despite
      the notable similarity in potential factors responsible for host invasion and
      antibiotic resistance, other factors including several crucial virulence factors
      and heat shock proteins were absent in the plant-associated DSM14405T. Instead,
      S. rhizophila DSM14405T possessed unique genes for the synthesis and transport of
      the plant-protective spermidine, plant cell-wall degrading enzymes, and high
      salinity tolerance. Moreover, the presence or absence of bacterial growth at 37
      degrees C was identified as a very simple method in differentiating between
      pathogenic and non-pathogenic isolates. DSM14405T is not able to grow at this
      human-relevant temperature, most likely in great part due to the absence of heat
      shock genes and perhaps also because of the up-regulation at increased
      temperatures of several genes involved in a suicide mechanism. CONCLUSIONS: While
      this study is important for understanding the mechanisms behind the emerging
      pattern of infectious diseases, it is, to our knowledge, the first of its kind to
      assess the risk of beneficial strains for biotechnological applications. We
      identified certain traits typical of pathogens such as growth at the human body
      temperature together with the production of heat shock proteins as opposed to a
      temperature-regulated suicide system that is harnessed by beneficials.

PMID- 24939222
TI  - Transition of the NSW Public Health Bulletin to Public Health Research &
      Practice.

PMID- 24939221
TI  - The significance of Notch ligand expression in the peripheral blood of children
      with hand, foot and mouth disease (HFMD).
AB  - BACKGROUND: Hand, foot and mouth disease (HFMD), a virus-induced infectious
      disease that usually affects infants and children, has an increased incidence in
      China in recent years. This study attempted to investigate the role of the Notch
      signaling pathway in the pathogenesis of HFMD. METHODS: Eighty-two children
      diagnosed with HFMD were enrolled into this study. The HFMD group was further
      divided into the uncomplicated HFMD and HFMD with encephalitis groups. The
      control group included 40 children who underwent elective surgery for treatment
      of inguinal hernias. RESULTS: Children with HFMD displayed significantly reduced
      CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3-CD19+
      cell subset (p<0.05 versus control subjects). The expression levels of Notch
      ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were
      significantly higher than those in the control group (p<0.05). There were
      statistically significant differences in CD3+, CD3+CD4+ and CD3-CD19+ cell
      subsets, but not in Notch ligand expression, between the uncomplicated HFMD and
      HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated
      negatively with the CD3+ and CD3+CD8+ cell subsets (p<0.05), but positively with
      the CD3-CD19+ cell subset (p<0.05). Furthermore, Dll4 expression in HFMD with
      encephalitis subjects correlated positively with total white blood cell (WBC)
      counts and total protein contents in cerebrospinal fluid (CSF) (p<0.05).
      CONCLUSIONS: The Notch ligand Dll4 exhibits a strong correlation with the CD3+,
      CD3+CD8+ and CD3-CD19+ cell subsets in children with HFMD, indicating that the
      Notch signaling may be involved in the development of HFMD by affecting the
      number and status of peripheral lymphocytes.

PMID- 24939223
TI  - Reflections on 24 years of the NSW Public Health Bulletin.

PMID- 24939224
TI  - Reporting postpartum haemorrhage with transfusion: a comparison of NSW birth and
      hospital data.
AB  - AIM: Postpartum haemorrhage rates have been increasing in NSW and
      internationally, and blood transfusion is required in severe cases. Using
      routinely collected administrative data provides a convenient method with which
      to monitor trends in both postpartum haemorrhage and associated transfusion use.
      In order for this to be feasible however, the reliability of reporting of the
      conditions needs to be assessed. METHODS: This study used linked data to compare
      the reporting of postpartum haemorrhage with transfusion as reported in the NSW
      Admitted Patient Data Collection (hospital data), with the same information
      obtained from the Perinatal Data Collection (birth data), for births in NSW from
      2007 to 2010. RESULTS: The rate of postpartum haemorrhage requiring blood
      transfusion was 1.0% based on the hospital data and 1.1% based on the birth data,
      with a rate of 1.7% if identifying cases from either source. Agreement between
      the two sources improved from fair to moderate over the time period. CONCLUSION:
      Postpartum haemorrhage requiring transfusion recorded in the birth data shows
      only moderate agreement with hospital data, so caution is recommended when using
      this variable for analysis. Linkage of both datasets is recommended to identify
      birth information from birth data and postpartum haemorrhage with transfusion
      from hospital data until further validation work has been undertaken.

PMID- 24939225
TI  - Timeliness of Salmonella Typhimurium notifications after the introduction of
      routine MLVA typing in NSW.
AB  - Salmonella Typhimurium is the most common bacterial cause of gastrointestinal
      disease in NSW. Regular review of surveillance procedures ensures system
      objectives are met and informs improvements in system utility and efficiency.
      This paper assesses the timeliness and data completeness of NSW Salmonella
      Typhimurium surveillance after the routine introduction of multilocus variable
      repeat analysis (MLVA), a rapid sub-typing technique. MLVA results were available
      significantly earlier than alternate sub-typing techniques over the 2 years of
      this review. Accordingly, from a timeliness perspective, MLVA offers a favourable
      Salmonella Typhimurium sub-typing option in NSW. Further opportunities to improve
      timeliness and data completeness are identified. This paper was produced as part
      of a review of Salmonella Typhimurium surveillance in NSW for the period 2008
      2009 by members of OzFoodNet based at Hunter New England Population Health.
      OzFoodNet is a national network established by the then Commonwealth Department
      of Health and Ageing in 2000 to enhance foodborne disease surveillance in
      Australia. 

PMID- 24939226
TI  - Public and private dental services in NSW: a geographic information system
      analysis of access to care for 7 million Australians.
AB  - AIM: To investigate the distribution of public and private dental practices in
      NSW in relation to population distribution and socioeconomic status. METHODS:
      Dental practices (public and private) were mapped and overlayed with Census data
      on Collection District population and Socio-Economic Indexes for Areas (SEIFA).
      RESULTS: Overall, there was an uneven geographic distribution of public and
      private dental practices across NSW. When the geographic distribution was
      compared to population socioeconomics it was found that in rural NSW, 12% of the
      most disadvantaged residents lived further than 50km from a public dental
      practice, compared to 0% of the least disadvantaged. In Sydney, 9% of the three
      most disadvantaged groups lived greater than 7.5km from a public dental practice,
      compared to 21% of the three least disadvantaged groups. CONCLUSION: The findings
      of this study can contribute to informing decisions to determine future areas for
      focus of dental resource development (infrastructure and workforce) and
      identifying subgroups in the population (who are geographically isolated from
      accessing care) where public health initiatives focused on amelioration of
      disease consequences should be a focus.

PMID- 24939227
TI  - Infectious diseases in returned travellers, NSW, 2010-2011.
AB  - AIM: To quantify the proportion of selected notified diseases in NSW attributable
      to overseas travel and assess the quality of data on travel-associated risk
      factors, to inform prevention strategies. METHODS: 2010 and 2011 notification
      data for dengue, hepatitis A, hepatitis E, malaria, paratyphoid fever,
      shigellosis and typhoid fever were extracted from the NSW Notifiable Conditions
      Information Management System and analysed for travel-associated risk factors.
      RESULTS: Where place of acquisition was known, the proportion of cases for whom
      the disease was acquired overseas ranged from 48.7% for shigellosis to 100% for
      hepatitis E, malaria and typhoid. Over half of hepatitis A (53.3%), hepatitis E
      (74.2%), malaria (54.5%), paratyphoid (53.3%) and typhoid (65.7%) cases were
      associated with travel to the person's country of birth. Hepatitis A vaccination
      rates were significantly lower among overseas-acquired than locally-acquired
      cases (4.8% vs 22.2%, Chi(2)=6.58, p<0.02). CONCLUSION: A large proportion of
      selected enteric and vectorborne disease case notifications were associated with
      overseas travel. All potential travellers should be made aware of the risks and
      available preventive measures, such as vaccination against hepatitis A and
      typhoid fever, taking precautions with food and water and use of malaria
      chemoprophylaxis, where appropriate. Improvements in data on risk factors, reason
      for travel and barriers to the use of preventive measures would better inform
      prevention strategies.

PMID- 24939230
TI  - Communicable Diseases Report, NSW, July-September 2013.

PMID- 24939233
TI  - All-optical regulation of gene expression in targeted cells.
AB  - Controllable gene expression is always a challenge and of great significance to
      biomedical research and clinical applications. Recently, various approaches based
      on extra-engineered light-sensitive proteins have been developed to provide
      optogenetic actuators for gene expression. Complicated biomedical techniques
      including exogenous genes engineering, transfection, and material delivery are
      needed. Here we present an all-optical method to regulate gene expression in
      targeted cells. Intrinsic or exogenous genes can be activated by a Ca(2+)
      sensitive transcription factor nuclear factor of activated T cells (NFAT) driven
      by a short flash of femtosecond-laser irradiation. When applied to mesenchymal
      stem cells, expression of a differentiation regulator Osterix can be activated by
      this method to potentially induce differentiation of them. A laser-induced
      "Ca(2+)-comb" (LiCCo) by multi-time laser exposure is further developed to
      enhance gene expression efficiency. This noninvasive method hence provides an
      encouraging advance of gene expression regulation, with promising potential of
      applying in cell biology and stem-cell science. 

PMID- 24939235
TI  - The influence of cueing on attentional focus in perceptual decision making.
AB  - Selective attention has been known to play an important role in decision making.
      In the present study, we combined a cueing paradigm with a redundant-target
      detection task to examine how attention affects the decision process when
      detecting the redundant targets. Cue validity was manipulated in two experiments.
      The results showed that when the cue was 50 % valid in one experiment, the
      participants adopted a parallel self-terminating processing strategy, indicative
      of a diffuse attentional focus on both target locations. When the cue was 100 %
      valid in the second experiment, all of the participants switched to a serial self
      terminating processing strategy, which in our study indicated focused attention
      to a single target location. This study demonstrates the flexibility of the
      decision mechanism and highlights the importance of top-down control in selecting
      a decision strategy.

PMID- 24939234
TI  - Generating a taxonomy of spatially cued attention for visual discrimination:
      effects of judgment precision and set size on attention.
AB  - Attention precues improve the performance of perceptual tasks in many but not all
      circumstances. These spatial attention effects may depend upon display set size
      or workload, and have been variously attributed to external noise filtering,
      stimulus enhancement, contrast gain, or response gain, or to uncertainty or other
      decision effects. In this study, we document systematically different effects of
      spatial attention in low- and high-precision judgments, with and without external
      noise, and in different set sizes in order to contribute to the development of a
      taxonomy of spatial attention. An elaborated perceptual template model (ePTM)
      provides an integrated account of a complex set of effects of spatial attention
      with just two attention factors: a set-size dependent exclusion or filtering of
      external noise and a narrowing of the perceptual template to focus on the signal
      stimulus. These results are related to the previous literature by classifying the
      judgment precision and presence of external noise masks in those experiments,
      suggesting a taxonomy of spatially cued attention in discrimination accuracy. 

PMID- 24939236
TI  - Effects of spatial configurations on the resolution of spatial working memory.
AB  - Recent research demonstrated that people represent spatial information
      configurally and preservation of configural cues at retrieval helps memory for
      spatial locations (Boduroglu & Shah, Memory & Cognition, 37(8), 1120-1131 2009;
      Jiang, Olson, & Chun, Journal of Experimental Psychology: Learning, Memory, and
      Cognition, 26(3), 683-702 2000). The present study investigated the effects of
      spatial configurations on the resolution of individual location representations.
      In an open-ended task, participants first studied a set of object locations
      (three and five locations). Then, in a test display where available configural
      cues were manipulated, participants were asked to determine the original location
      of a target object whose color was auditorially cued. The difference between the
      reported location and the original location was taken as a measure of spatial
      resolution. In three experiments, we consistently observed that the resolution of
      spatial representations was facilitated by the preservation of spatial
      configurations at retrieval. We argue that participants may be using available
      configural cues in conjunction with the summary representation (e.g., centroid)
      of the original display in the computation of target locations.

PMID- 24939237
TI  - No evidence that 'fast-mapping' benefits novel learning in healthy Older adults.
AB  - Much evidence suggests that the Hippocampus is necessary for learning novel
      associations. Contrary to this, Sharon, Moscovitch, and Gilboa (2011) reported
      four amnesic patients with Hippocampal damage who maintained the capacity to
      learn novel object-name associations when trained with a 'fast-mapping' (FM)
      technique. This technique therefore potentially offers an alternative route for
      learning novel information in populations experiencing memory problems. We
      examined this potential in healthy ageing, by comparing 24 Older and 24 Young
      participants who completed a FM procedure very similar to Sharon et al. (2011).
      As expected, the Older group showed worse memory than the Young group under
      standard explicit encoding (EE) instructions. However, the Older group continued
      to show worse performance under the FM procedure, with no evidence that FM
      alleviated their memory deficit. Indeed, performance was worse for the FM than EE
      condition in both groups. Structural MRI scans confirmed reduced Hippocampal grey
      matter volume in the Older group, which correlated with memory performance across
      both groups and both EE/FM conditions. We conclude FM does not help memory
      problems that occur with normal ageing, and discuss theoretical implications for
      memory theories. 

PMID- 24939239
TI  - Soy intake and endometrial cancer risk varies according to study population.

PMID- 24939240
TI  - Hydrogen storage in a potassium-ion-bound metal-organic framework incorporating
      crown ether struts as specific cation binding sites.
AB  - To develop a metal-organic framework (MOF) for hydrogen storage, SNU-200
      incorporating a 18-crown-6 ether moiety as a specific binding site for selected
      cations has been synthesized. SNU-200 binds K(+), NH4(+), and methyl viologen
      (MV(2+)) through single-crystal to single-crystal transformations. It exhibits
      characteristic gas-sorption properties depending on the bound cation. SNU-200
      activated with supercritical CO2 shows a higher isosteric heat (Qst) of H2
      adsorption (7.70 kJ mol(-1)) than other zinc-based MOFs. Among the cation
      inclusions, K(+) is the best for enhancing the isosteric heat of the H2
      adsorption (9.92 kJ mol(-1)) as a result of the accessible open metal sites on
      the K(+) ion.

PMID- 24939241
TI  - [Pain medicine as a cross-sectional subject in German medical schools. An
      opportunity for general pain management].
AB  - BACKGROUND: Unrelieved pain is a substantial public health concern owing in part
      to deficits in clinical expertise among physicians. In most medical faculties
      worldwide, teaching on pain and pain management is either nonexistent or limited
      to a small number of students attending voluntary courses. In light of the fact
      that pain is the most frequent reason to seek medical advice, the lack of formal
      training of pain medicine is considered the leading reason for inadequate pain
      management. Therefore, the patients' unmet needs for adequate diagnosis and
      therapy call for action. SITUATION: Pain assessment and effective pain management
      should be a priority in the health care system. The limited number of pain
      specialists available in hospitals and primary care and CME (continuous medical
      education) activities focusing on pain are not sufficient to solve the problem.
      Every practicing physician should, therefore, have basic knowledge of the most
      prominent painful conditions and management strategies. To achieve this goal,
      pain medicine should become an integral part of the undergraduate curriculum for
      medical students. In Germany, pain medicine became a mandatory subject in
      undergraduate medical studies in 2012. PERSPECTIVE: The introduction of pain
      medicine into the undergraduate curriculum in Germany is a major challenge
      regarding the development and implementation processes. This article describes
      current instruments and implementation strategies for pain medicine as a new
      cross-sectional subject in Germany.

PMID- 24939243
TI  - The effect of the height to which the hand is lifted on horizontal curvature in
      horizontal point-to-point movements.
AB  - In point-to-point reaching movements, the trajectory of the fingertip along the
      horizontal plane is not completely straight but slightly curved sideward. The
      current paper examines whether this horizontal curvature is related to the height
      to which the finger is lifted. Previous research suggested that the height to
      which the hand is lifted might be a determinant of horizontal curvature. We asked
      participants to make point-to-point movements in three conditions: constrained
      movements (i.e., fingertip keeps contact with table top) over vertically curved
      surfaces that differed in height, constrained movements over a flat surface, and
      unconstrained movements (i.e., fingertip lifted from table top). In constrained
      movements, we found a strong relation between horizontal curvature and lifted
      height of the finger. Interestingly, for unconstrained movements, the relation
      between horizontal curvature and height to which the finger was lifted was weak.
      This demonstrates that the height to which the finger was lifted relates to
      horizontal curvature in some, but not in all conditions. This suggests that the
      height to which the hand is lifted should be included, in particular for
      constrained movements, when giving a full account of horizontal curvature in
      point-to-point movements.

PMID- 24939242
TI  - [Capsaicin 8 % cutaneous patches for phantom limb pain. Results from everyday
      practice (non-interventional study)].
AB  - BACKGROUND: Post amputation pain presents a challenge for pain physicians and is
      often detrimental to the patient's quality of life. PATIENTS AND METHODS: A
      prospective 12-week non-interventional study (NIS) was conducted in Germany to
      obtain data on the effectiveness and safety of capsaicin 8 % cutaneous patches
      from real life use in patients with peripheral neuropathic pain. For the first
      time in a subgroup of amputees data on post amputation pain were collected. This
      article presents the results for patients who suffered from phantom limb pain
      (PLP), stump pain (SP) and combined phantom limb/stump pain (PLP/SP). RESULTS:
      The analyses included 21 patients with post amputation pain (PLP: n = 10, SP: n =
      4, PLP/SP: n = 7). The mean duration of pain (+/- standard deviation) was 12.8 +/
      13.0 years for PLP, 23.1 +/- 29.9 years for SP and 11.0 +/- 15.8 years for
      PLP/SP. A single treatment with capsaicin 8 % cutaneous patches significantly
      reduced the average pain intensity over the observational period of 12 weeks. The
      mean numeric pain rating scale (NPRS) baseline score changed by - 2.4 for PLP
      with a standard error of the mean (SEM) of 0.4 (median: - 2.9, Q1: - 3.5, Q3: -
      1.0), - 1.7 for SP (SEM: 0.8, median: - 1.1, Q1: - 2.9, Q3: - 0.5) and - 1.5 for
      PLP/SP (SEM: 0.6, median: - 2.0, Q1: - 2.3, Q3: 0) during weeks 1-12. The 30 %
      responder rates (i.e. >= 30 % reduction in pain, day 7/14 to week 12) were 70.0 %
      (PLP), 50.0 % (SP) and 28.6 % (PLP/SP). PLP and PLP/SP patients in particular,
      benefited from improvements in pain attacks, sleep duration and sleep quality and
      one patient (PLP/SP) reported an adverse drug reaction (increase of pain).
      Physicians rated the tolerability of the patch as very good or good in 90.5 % of
      patients. A poor tolerability was stated for none of the 21 amputees. Of the
      patients 80 % for PLP and 50 % for both SP and PLP/SP expressed the wish to
      receive retreatment with capsaicin 8 % patches. CONCLUSION: Capsaicin 8 %
      cutaneous patches seem to be effective and safe for the treatment of post
      amputation pain, notably in patients suffering from phantom limb pain.

PMID- 24939244
TI  - Template-mediated nano-crystallite networks in semiconducting polymers.
AB  - Unlike typical inorganic semiconductors with a crystal structure, the charge
      dynamics of pi-conjugated polymers (pi-CPs) are severely limited by the presence
      of amorphous portions between the ordered crystalline regions. Thus, the
      formation of interconnected pathways along crystallites of pi-CPs is desired to
      ensure highly efficient charge transport in printable electronics. Here we report
      the formation of nano-crystallite networks in pi-CP films by employing novel
      template-mediated crystallization (TMC) via polaron formation and electrostatic
      interaction. The lateral and vertical charge transport of TMC-treated films
      increased by two orders of magnitude compared with pristine pi-CPs. In
      particular, because of the unprecedented room temperature and solution-processing
      advantages of our TMC method, we achieve a field-effect mobility of 0.25 cm(2) V(
      1) s(-1) using a plastic substrate, which corresponds to the highest value
      reported thus far. Because our findings can be applied to various pi-conjugated
      semiconductors, our approach is universal and is expected to yield high
      performance printable electronics. 

PMID- 24939238
TI  - Fast food fever: reviewing the impacts of the Western diet on immunity.
AB  - While numerous changes in human lifestyle constitute modern life, our diet has
      been gaining attention as a potential contributor to the increase in immune
      mediated diseases. The Western diet is characterized by an over consumption and
      reduced variety of refined sugars, salt, and saturated fat. Herein our objective
      is to detail the mechanisms for the Western diet's impact on immune function. The
      manuscript reviews the impacts and mechanisms of harm for our over-indulgence in
      sugar, salt, and fat, as well as the data outlining the impacts of artificial
      sweeteners, gluten, and genetically modified foods; attention is given to
      revealing where the literature on the immune impacts of macronutrients is limited
      to either animal or in vitro models versus where human trials exist. Detailed
      attention is given to the dietary impact on the gut microbiome and the mechanisms
      by which our poor dietary choices are encoded into our gut, our genes, and are
      passed to our offspring. While today's modern diet may provide beneficial
      protection from micro- and macronutrient deficiencies, our over abundance of
      calories and the macronutrients that compose our diet may all lead to increased
      inflammation, reduced control of infection, increased rates of cancer, and
      increased risk for allergic and auto-inflammatory disease. 

PMID- 24939245
TI  - Preconception counseling, fertility, and pregnancy complications after abdominal
      organ transplantation: a survey and cohort study of 532 recipients.
AB  - BACKGROUND: Pregnancy after solid organ transplant is a significant priority for
      transplant recipients but how patients report being counseled is unknown.
      METHODS: We performed a single-center retrospective cohort study and telephone
      survey of female patients ages 18-49 at the time of kidney, pancreas, or liver
      transplant from 2000 to 2012 (n = 532). Data on pregnancy counseling, fertility,
      and maternal, fetal- and transplant-specific outcomes were collected.
      Multivariate Cox models assessed the impact of pregnancy on graft-specific
      outcomes. RESULTS: The survey response rate was 29% (n = 152). One-third (n = 51)
      of women were actively counseled against pregnancy by one or more providers. A
      total of 17 pregnancies occurred among nine patients (5.9%), with 47% live
      births, 47% early embryonic demises, 5.9% stillbirths. Of live births, 50% were
      premature. Gestational complications, including diabetes, hypertension, and
      preeclampsia were present in 88% of mothers. Pregnancy after transplant was
      associated with higher rates of acute rejection than nulliparous transplant
      recipients (33% vs. 5.6%, p = 0.07) but did not significantly affect graft
      survival (HR = 1.00, 95% CI 0.99-1.01), after stratifying by organ and adjusting
      for clinical factors. CONCLUSION: This study suggests that transplant patients
      are being counseled against pregnancy despite acceptable risks of complications
      and no specific effects on long-term graft function.

PMID- 24939246
TI  - Genomic characterization of ependymomas reveals 6q loss as the most common
      aberration.
AB  - Ependymomas are rare tumors of the central nervous system (CNS). They are
      classified based on tumor histology and grade, but the prognostic value of the
      WHO grading system remains controversial. Treatment is mainly surgical and by
      radiation. An improved knowledge of ependymoma biology is important to elucidate
      the pathogenesis, to improve classification schemes, and to identify novel
      potential treatment targets. Only 113 ependymoma karyotypes with chromosome
      aberrations are registered in the Mitelman database. We present the first study
      of ependymoma genomes combining karyotyping and high resolution comparative
      genomic hybridization (HR-CGH). Nineteen tumor samples were collected from three
      pediatric and 15 adult patients treated at Oslo University Hospital between 2005
      and 2012. Histological diagnoses included subependymoma and myxopapillary
      ependymoma (WHO grade I), ependymoma (WHO grade II) and anaplastic ependymoma
      (WHO grade III). Four tumors were intraspinal and 15 were intracranial. Seventeen
      samples were successfully karyotyped, HR-CGH analysis was undertaken on 17
      samples, and 15 of 19 tumors were analyzed using both methods. Twelve tumors had
      karyotypic abnormalities, mostly gains or losses of whole chromosomes. Structural
      rearrangements were found in four tumors, in two of which 2p23 was identified as
      a breakpoint region. Twelve tumors displayed genomic imbalances by HR-CGH
      analysis with loss of material at 6q as the most common. 6q loss, which was
      detected by one or both methods in seven of 12 (58%) abnormal tumors, and 5p gain
      (observed in five tumors; 42%) were the most common genomic aberrations in this
      series.

PMID- 24939247
TI  - Novel synaptic memory device for neuromorphic computing.
AB  - This report discusses the electrical characteristics of two-terminal synaptic
      memory devices capable of demonstrating an analog change in conductance in
      response to the varying amplitude and pulse-width of the applied signal. The
      devices are based on Mn doped HfO2 material. The mechanism behind reconfiguration
      was studied and a unified model is presented to explain the underlying device
      physics. The model was then utilized to show the application of these devices in
      speech recognition. A comparison between a 20 nm * 20 nm sized synaptic memory
      device with that of a state-of-the-art VLSI SRAM synapse showed ~10* reduction in
      area and >10(6) times reduction in the power consumption per learning cycle.

PMID- 24939248
TI  - Functional characterization of neural-restrictive silencer element in mouse
      pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is predominantly
      localized in the nervous system, but the underlying mechanism in its neuron
      specific expression remains unclear. In addition to two neural-restrictive
      silencer-like element (NRSLE1 and 2), as reported previously, we have identified
      the third element in -1,601 to -1,581 bp from the translational initiation site
      of mouse PACAP gene and termed it as NRSLE3, of which, the sequence and location
      were highly conserved among mouse, rat, and human PACAP genes. In luciferase
      reporter assay, the deletion or site-directed mutagenesis of NRSLE3 in the
      reporter gene construct, driven by heterologous SV40 promoter, cancelled the
      repression of luciferase activity in non-neuronal Swiss-3T3 cells. Furthermore,
      its promoter activity was significantly repressed in Swiss-3T3 cells, but not in
      neuronal-differentiated PC12 cells. The electrophoretic mobility shift assay
      (EMSA) with nuclear extracts of Swiss-3T3 cells demonstrated a specific complex
      with NRSLE3 probe that exhibited the same migration with the neural-restrictive
      silencer element (NRSE) probe of rat type II sodium channel gene. During neuronal
      differentiation of PC12 cells, the increment of PACAP mRNA exhibited the
      correlation with that of REST4 mRNA, which is a neuron-specific variant form of
      neural-restrictive silencer factor (NRSF). In undifferentiated PC12 cells,
      trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which indirectly
      inhibits NRSF-mediated gene silencing, increased PACAP mRNA level and attenuated
      the repression of promoter activity of 5' flanking region of mouse PACAP gene
      containing NRSLEs. These suggest that the NRSE-NRSF system implicates in the
      regulatory mechanism of neuron-specific expression of PACAP gene. 

PMID- 24939250
TI  - An alternative method for registering the abutment screw position of cement
      retained implant restorations.

PMID- 24939249
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) induces relaxations of
      peripheral and cerebral arteries, which are differentially impaired by aging.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known
      neuropeptide, which also has vasomotor effects. However, little is known
      regarding its age-related and organ-specific vasomotor effects. We hypothesized
      that the vasomotor effects of PACAP depend on the tissue origin of the vessels
      and aging substantially modulates its actions. Thus, carotid (CA) and basilar
      arteries (BA) were isolated from young (2 months old), middle age (12 months
      old), and old (30 months old) rats. Their vasomotor responses were measured with
      an isometric myograph (DMT610M) in response to cumulative concentrations of
      PACAP1-38 (10(-9)-10(-6) M). PACAP1-38 induced (1) significantly greater
      concentration-dependent relaxations in CA compared to that of BA of young, middle
      age, and old rats; (2) relaxations of CA significantly decreased, whereas they
      did not change substantially in BA, as a function of age; (3) sodium
      nitroprusside (SNP)-induced relaxation did not change after PACAP1-38
      administration in any conditions; and (4) inhibition of PAC1 receptors by
      selective PAC1 receptor blocker (PACAP6-38) completely diminished the responses
      to PACAP in all age groups of BA and CA. In conclusion, these findings suggest
      that PACAP1-38 has greater vasomotor effect in CA than that in BA, whereas aging
      has less effect on PACAP-induced relaxation of cerebral arteries and BA than that
      in peripheral arteries and CA suggesting that the relaxation to PACAP is
      maintained in cerebral arteries even in old age. 

PMID- 24939251
TI  - Use of direct-indirect method for fabrication of tooth-retained overdenture stud
      attachments.

PMID- 24939252
TI  - Immediate implant placement, reconstruction of compromised sockets, and repair of
      gingival recession with a triple graft from the maxillary tuberosity: a variation
      of the immediate dentoalveolar restoration technique.
AB  - Immediate implant placement into compromised sockets is challenging for
      clinicians. The 3-dimensional implant position, status of the buccal bone wall,
      and regeneration of the soft tissue contours all affect adequate esthetic and
      functional results. This clinical report presents a treatment protocol (a
      variation of the immediate dentoalveolar restoration concept) consisting of
      immediate implantation and the reconstruction of the buccal bone wall and
      gingival recession in a single procedure with a triple graft (cancellous and
      cortical bone and soft tissue graft).

PMID- 24939253
TI  - Design and manufacture of customized dental implants by using reverse engineering
      and selective laser melting technology.
AB  - STATEMENT OF PROBLEM: Recently a new therapeutic concept of patient-specific
      implant dentistry has been advanced based on computer-aided design/computer-aided
      manufacturing technology. However, a comprehensive study of the design and 3
      dimensional (3D) printing of the customized implants, their mechanical
      properties, and their biomechanical behavior is lacking. PURPOSE: The purpose of
      this study was to evaluate the mechanical and biomechanical performance of a
      novel custom-made dental implant fabricated by the selective laser melting
      technique with simulation and in vitro experimental studies. MATERIAL AND
      METHODS: Two types of customized implants were designed by using reverse
      engineering: a root-analog implant and a root-analog threaded implant. The
      titanium implants were printed layer by layer with the selective laser melting
      technique. The relative density, surface roughness, tensile properties, bend
      strength, and dimensional accuracy of the specimens were evaluated. Nonlinear and
      linear finite element analysis and experimental studies were used to investigate
      the stress distribution, micromotion, and primary stability of the implants.
      RESULTS: Selective laser melting 3D printing technology was able to reproduce the
      customized implant designs and produce high density and strength and adequate
      dimensional accuracy. Better stress distribution and lower maximum micromotions
      were observed for the root-analog threaded implant model than for the root-analog
      implant model. In the experimental tests, the implant stability quotient and pull
      out strength of the 2 types of implants indicated that better primary stability
      can be obtained with a root-analog threaded implant design. CONCLUSIONS:
      Selective laser melting proved to be an efficient means of printing fully dense
      customized implants with high strength and sufficient dimensional accuracy.
      Adding the threaded characteristic to the customized root-analog threaded implant
      design maintained the approximate geometry of the natural root and exhibited
      better stress distribution and primary stability.

PMID- 24939254
TI  - Effect of different surface-cleaning techniques on the bond strength of composite
      resin restorations.
AB  - STATEMENT OF PROBLEM: Different techniques have been suggested for cleaning
      dentin surfaces after the removal of an interim prosthesis and before the
      application of a bonding agent. How different surface-cleaning techniques affect
      the bond strength of the composite resin restorations is not clear. PURPOSE: The
      purpose of this study was to investigate the effects of different surface
      cleaning techniques on the bond strength of composite resin restorations and the
      surface topography of the prepared tooth surfaces. MATERIAL AND METHODS: The
      occlusal surfaces of 25 molars were ground until the dentin was exposed. A
      bonding agent and interim cement were applied on the teeth. The teeth were
      divided into 5 groups (n=5) according to the method used for surface-cleaning
      (microairborne-particle abrasion, alcohol, rubber-rotary instrument, desiccating
      agent, and control). Once the surfaces of the teeth had been cleaned, the same
      bonding material was applied to the teeth. A 5-mm-thick composite resin layer was
      built up. Each specimen was sectioned to microbars, and 6 centrally located beams
      were selected for microtensile testing (n=30) (1.10 +/-0.10 mm). The data were
      statistically analyzed with 1-way ANOVA (1-sample Kolmogorov-Smirnov test). The
      Bonferroni test was used for significantly different groups (alpha=.05). One
      specimen from each group was observed under a scanning electron microscope and an
      atomic force microscope. Energy dispersive x-ray analysis also was performed.
      RESULTS: Bond strength values were in the following descending order:
      microairborne-particle abrasion, desiccating agent, alcohol, rubber-rotary
      instrument, control. Differences between the microairborne-particle abrasion
      group and the remainder of the groups, desiccating agent--rubber-rotary
      instrument, desiccating agent-control, alcohol--rubber-rotary instrument, and
      alcohol-control groups, were statistically significant (P<.05). The microairborne
      particle abrasion group displayed the roughest surface and a different surface
      topography from the remainder of the groups. Increased aluminum was observed in
      the microairborne-particle abrasion group. CONCLUSIONS: Surface-cleaning
      techniques, except for the rubber-rotary instrument, increased the bond strength
      of composite resin. The roughest dentin surfaces and highest bond strength were
      achieved with the microairborne-particle abrasion technique.

PMID- 24939255
TI  - High-dose folic acid improves endothelial function by increasing
      tetrahydrobiopterin and decreasing homocysteine levels.
AB  - The aim of this study was to investigate the effect of folic acid (FA) on
      tetrahydrobiopterin (BH4), neopterin, nitric oxide (NO) and homocysteine (Hcy)
      levels in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were
      cultured in vitro in the presence or absence of Hcy. The effect of various doses
      of FA on Hcy, BH4, neopterin and NO concentrations in HUVECs was then assessed.
      In the 5 and 10 nmol/l FA treatment groups, FA was found to significantly
      increase the levels of BH4 (10.56+/-3.86 and 11.23+/-2.1919 pmol/g vs 6.32+2.87
      nmol/g; P<0.05 vs. control) and NO production (37.86+/-12.34 nmol/l, 38.45+/
      11.23 nmol/l vs 26.21+/-9.24 nmol/l; P<0.001 vs. paired Hcy group), but reduce
      the levels of Hcy (132.87+/-29.67 and 140.87+/-26.76 nmol/l vs. 165.23+/-30.56
      nmol/l; P<0.05 vs. Hcy group). No significant differences were observed in
      neopterin levels among the different groups of HUVECs. In conclusion, high doses
      of FA may be capable of protecting endothelial cells through reducing levels of
      Hcy and increasing BH4 and NO production. 

PMID- 24939256
TI  - An analysis of biopsy-proven tongue lesions among 8,105 dental outpatients.
AB  - AIM: The aim of the present study was to analyze data on the characteristics of
      tongue lesions in dental patients seeking care at the Oral Pathology Service of
      Tehran University of Medical Sciences, from 1985-2010. MATERIALS AND METHODS:
      Demographic data and histopathologic diagnoses were recorded for all lesions that
      were documented as occurring on the tongue according to the patient records in
      our department. Statistical analysis included chi-square, t-, and Fisher's exact
      tests. A 95% confidence interval (CI) was calculated, and p < 0.05 was considered
      significant. RESULTS: Tongue lesions constituted 6.3% of all received specimens
      which included 46 different defects. The most common lesions were lichen planus
      (LP), irritation fibroma (IF), squamous cell carcinoma (SCC) and pemphigus
      vulgaris (PV). Tongue lesions were significantly more common in women compared to
      men (CI = 0.65-0.94, p = 0.02). Mean age (47 years) did not differ between male
      and female subjects (CI = -2.49 - 3.93, p = 0.06). The dorsal surface followed by
      the lateral aspect was the most common site for tongue lesions. CONCLUSION: It
      seems that dental practitioners should be perceptive of LP, IF, SCC and PV, when
      examining the tongue. Histopathologic analysis is essential for achieving final
      diagnosis in a considerable number of lesions that commonly occur on this organ.
      Clinical significance: Access to demographic/prevalence data in different
      populations may be useful in clinical settings and could be complimented by
      histopathologic diagnosis in most instances. The present findings can be compared
      with those obtained from other epidemiologic studies in this field resulting in
      valuable data which may be used in several types of investigations. .

PMID- 24939257
TI  - Evaluation of protective effect of propolis on parotid salivary glands in gamma
      irradiated rats.
AB  - OBJECTIVE AND BACKGROUND: One of the most significant side effects of
      radiotherapy for head and neck cancers is xerostomia as a result of salivary
      gland damage. Considering pharmaco- logical effects of propolis, we evaluated its
      protective effect on salivary glands subjected to radiotherapy of head and neck
      cancer patients. MATERIALS AND METHODS: Twenty-one male albino rats (8-11 W, 190
      +/- 5 gm) were divided into three groups of seven animals. Scintigraphy was
      performed in all the groups. Then groups 1 (S) and 2 (SR) received normal saline
      injections and group 3 (PR) received propolis injection over 3 days. After that
      groups 2 and 3 were exposed to gamma radiation and all the rats underwent
      scintigraphic assessment on third day and 70th day after irradiation. The lips
      and tongues of rats in groups 2 and 3 were examined for mucositis daily in first
      10 days. At the end, the parotid glands of all rats were examined histologically.
      RESULTS: Scintigraphy results of third and 70th day after irradiation showed
      statistically significant differences between PR and SR as well as SR and S.
      However, there was no significant difference between the PR and S groups.
      Histopathologic assessment demonstrated significant difference between SR, PR and
      S. CONCLUSION: These results suggest that propolis has protective effects on
      salivary gland function in animal models whilst it did not prevent radiation
      induced histologic changes in tissues. Further investigations are needed to
      elucidate mechanisms of propolis actions. Clinical significance: Regarding to the
      results of this study, propolis may be useful in reduction xerostomia due to
      radiation to salivary glands and may be helpful for head and neck cancer
      patients.

PMID- 24939258
TI  - Obtaining artificially caries-affected dentin for in vitro studies.
AB  - AIM: This study evaluated and improved a protocol for obtaining standard caries
      affected dentin (CAD) by Streptococcus mutans biofilm demineralization process.
      MATERIALS AND METHODS: Forty-eight human molars were divided in six experimental
      groups, according to: period of cariogenic challenge (7, 14 or 21 days) and type
      of dentin (erupted or unerupted teeth). After complete cariogenic challenge sound
      and CAD dentin were evaluated by: visual inspection (VI), digital radiography
      (DR), optical coherence tomography (OCT) and laser fluorescence (LF). RESULTS:
      Visual inspection confirmed the formation of CAD based on tissue yellowing and
      loss of surface gloss. Digital radiography detected the presence of radiolucent
      images, suggesting caries. Three calibrated examiners viewed all images obtained
      by VI and DR and were able to distinguish healthy from CAD. Fisher's exact
      statistical test (p < 0.05) confirmed no difference between groups by VI (G1/G4:
      p = 0.6; G2/G5: p = 1; G3/G6: p = 1) or DR (G1/G4: p = 1; G2/G5: p = 1; G3/G6: p
      = 1). Both LF values and demineralization depth, as determined by OCT, were
      subjected to ANOVA (p < 0.05). For LF, a statistically significant difference was
      observed for the type of substrate (p = 0.001). For OCT, no statistically
      significant differences in the type of substrate (p = 0.163), length of
      cariogenic challenge (p = 0.512) or interaction between factors (p = 0.148) were
      observed. Scanning electron micrographs confirmed the presence of CAD; a more
      uniform demineralization surface was observed in the dentin of unerupted teeth.
      CONCLUSION: This protocol suggests that standard CAD can be obtained in 7 days of
      cariogenic challenge using unerupted teeth. Clinical significance: With the new
      perspective on the clinical treatment of caries lesions, bonding is increasingly
      performed to demineralize CAD, which is susceptible to remineralization. A useful
      protocol to standardize the production of CAD, by microbiological cariogenic
      challenge, would be an important contribution to laboratorial test in the field
      of operative dentistry.

PMID- 24939259
TI  - Comparative evaluation of cariogenic and erosive potential of commonly prescribed
      pediatric liquid medicaments: an in vitro study.
AB  - INTRODUCTION: Liquid oral medicines being the most accepted form of medication in
      children are frequently prescribed. The harmful effects of these liquid
      medicaments on a child's dental health are not known to many. The present study
      aimed to evaluate and compare the cariogenic and erosive potential of 5 most
      commonly prescribed pediatric liquid medicaments (PLM) in Pimpri Chinchwad and
      Pune city, Pune district. MATERIALS AND METHODS: Most commonly prescribed PLM in
      Pune district were selected as opined by 50 pediatricians. The selected
      medicaments were Syr. Augmentin(r) Duo, Syr. Valparin(r), Syr. Combiflam(r), Syr.
      Visyneral and Syr. Orofer(r). An estimation of pH, percentage of sucrose
      concentration and calcium dissolving capacity of these preparations was carried
      out. The results as obtained were subjected to statistical analysis using SPSS v
      17.0 for windows. The statistical test as undertaken was Pearson's correlation
      coeffcient(r). RESULTS: Sucrose was seen to be present in Syr. Combiflam(r)
      (35.75% +/- 0.25%) and Syr. Visyneral (18.48% +/- 0.43%). Acidic pH was observed
      for Syr. Visyneral (mean pH 3.63 +/- 0.04), Syr. Combiflam(r)(mean pH 5.03 +/-
      0.02) and Syr. Augmentin(r) (mean pH 6.22 +/- 0.02). Highest calcium dissolution
      was seen with Syr. Combiflam(r)(295.86 mg/ml) and the least with Syr. Orofer(r)
      (25.51 mg/ml). No statistical significant correlation was observed with calcium
      dissolution potential of PLM in comparison with their respective pH. CONCLUSION:
      Syr. Combiflam(r) can be regarded as the highest cariogenic and erosive potential
      medicament among the compared and tested PLM. CLINICAL SIGNIFICANCE: Considering
      syrups with high cariogenic and erosive potential should always follow with
      proper oral hygiene practices or search for an alternative drugs void of such
      detrimental effects.

PMID- 24939260
TI  - Cuspal movement related to different polymerization protocols.
AB  - OBJECTIVE: The aim of this study to investigate the effects of different
      polymerization protocols on the cuspal movement in class II composite
      restorations. MATERIALS AND METHODS: Human premolar teeth were prepared with
      class II cavities and then restored with composite and three-step and two-step
      etch-and-rinse adhesive systems under different curing techniques (n = 10). It
      was used a light- emitting-diode curing unit and the mode of polymerization were:
      standard (exposure for 40 seconds at 700 mW/cm(2)), pulse-delay (initial exposure
      for 6 seconds at 350 mW/cm(2) followed by a resting period of 3 minutes and a
      final exposure of 37 seconds at 700 mW/cm(2)) and soft-start curing (exposure 10
      seconds at 350 mW/cm(2) and 35 seconds at 700 mW/cm(2)). The cuspal distance
      (MUm) was measured before and after the restorative procedure and the difference
      was recorded as cuspal movement. The data were submitted to two-way ANOVA and
      Bonferroni test (p < 0.05). RESULTS: The type of adhesive system did not
      influenced the cuspal movement for all the curing methods. Standard protocol
      showed the highest values of cuspal movement and was statistically different from
      the pulse-delay and soft-start curing modes. CONCLUSION: Although the cuspal
      displacement was not completely avoided, alternative methods of photocuring
      should be considered to minimize the clinical consequences of composites
      contraction stress.

PMID- 24939261
TI  - Association between the facial type and morphology of the upper central incisor
      in normal occlusion subjects.
AB  - AIM: The purpose of this study was to verify the association between the facial
      type and the morphology of the upper central incisor, to potentially provide a
      guide for artificial tooth selection in esthetic and prosthetic rehabilitation.
      MATERIALS AND METHODS: The sample consisted of 51 lateral teleradiographs
      (lateral cephalometric radiographs) and cast models of subjects with a naturally
      optimal occlusion and at least four of the six keys of Andrews, for optimal
      occlusion. The facial type was defined by two cephalometric measurements (SN.Gn
      and SN.GoGn) and classified into dolichofacial, meso- facial and brachyfacial
      after digitizing the radiographs. The incisor morphology was classified into
      quadrangular, oval and triangular after 3D digitizing the models and evaluation
      of the images by 12 dentists. The evaluation between the examiners was performed
      by Kappa test. In order to test the differences between the variables, it was
      used a chi-square test (5%). RESULTS: No significant difference (p < 0.05) was
      found between the studied variables. CONCLUSION: Facial type was not associated
      with the morphology of the upper central incisor, considering the methodology and
      population included in the present study. CLINICAL SIGNIFICANCE: Using the facial
      type as a way to select the morphology of the upper central incisor proved to be
      inadequate in this study.

PMID- 24939262
TI  - Wisdom tooth--complications in extraction.
AB  - The purpose of this study is to analyze the incidence of complications in a group
      of 171 patients in whom extractions of impacted mandibular third molar have been
      performed by two oral surgeons between the period April 2010 and March 2012. This
      retrospective study comprises evaluation of 270 impacted mandibular third molars
      which were classified into two groups A and B on the basis of procedure of
      osteotomy only and osteotomy and odontotomy both respectively. Total no of
      complications reported were 40 (14.81%). Maximum no of cases reported alveolar
      osteitis (AO) (11.11%) while other complications reported root tip fractures
      (2.22%), lingual nerve parasthesia and TMJ problems (each 0.74%) in descending
      frequency. Conclusion drawn is that the risk of complications in extractions of
      impacted mandibular third molars always exists, and extractions associated with
      both osteotomy and odontotomy are associated with higher risk of complications.

PMID- 24939263
TI  - Evaluation of marginal alveolar bone height for early detection of periodontal
      disease in pediatric population: clinical and radiographic study.
AB  - OBJECTIVES: To establish a normal range for the radiographic distance between
      cementoenamel junction and alveolar bone crest and the factors affecting
      distances for the early assessment of periodontal disease in Dravidian pediatric
      population. METHODS: Fifty children aged 6 to 8 years were selected based on
      inclusion and exclusion criteria. Clinical and radiographic examination was
      performed. All the surfaces were examined starting from the distal surface of
      primary canine to the mesial surface of first permanent molar. The various risk
      factors like plaque, calculus, proximal caries, restoration and bleeding on
      probing were recorded. A pair of bitewing radiographs was taken for each child.
      Bitewing radiographs were traced and analyzed. RESULTS: It showed that CEJ-ABC
      distance in primary teeth is about 1 +/- 0.5 mm. In the permanent teeth, it was
      found to be 0.6 +/- 0.5 mm in 6 to 8 years age group. CEJ-ABC distance was also
      affected by different variables like physiologic (eruption and exfoliation) and
      pathologic factors (plaque, calculus, dental caries, restorations, stainless
      steel crowns, bleeding on probing and probing depth). CONCLUSION: CEJ-ABC
      distances greater than 2.5 mm should be considered under recall and follow-up.
      Children and adolescents susceptible to periodontal disease should be identified
      by radiographic means as early as possible in order to prevent the advance of an
      otherwise possibly destructive disease. The concept of oral health examination
      and treatment must include examination of the periodontal status of the patient.

PMID- 24939264
TI  - Evaluation of occlusal contacts among different groups of malocclusion using 3D
      digital models.
AB  - OBJECTIVES: (1) To evaluate the applicability of using 3D digital models in the
      assessment of the magnitude of occlusal contacts by measuring occlusal contact
      surface areas (OCSAs) and 3D mesh points in 'contact' (OCMPs) in a sample of
      orthodontic patients; (2) To detect any sex differences in the magnitude of
      occlusal contacts in all malocclusion groups; (3) To detect inter- group
      differences; (4) To assess possible correlations between occlusal contacts and
      other dental characteristics. MATERIALS AND METHODS: Study casts of 120
      malocclusion patients were selected and divided into 4 groups (class I division
      1, class II division 1, class II division 2, class III) with equal numbers for
      both sexes. 3D digital models were produced using O3DMTM technology. Occlusal
      contacts were quantified using two methods of measuring. RESULTS: (1) No
      significant sexual differences were detected for OCMPs (mesh points) and OCSAs
      (mm(2)) in all groups. (2) There were statistically significant differences among
      malocclusion groups for OCMPs and OCSAs (p < 0.001). Tukey's HSD post- hoc tests
      showed that class III patients had significantly less occlusal contacts than
      other malocclusion groups. (3) Stepwise multiple regression equations showed that
      overjet, lower arch width and overbite could explain approximately 19.5% of the
      total variance of OCSAs and OCMPs. CONCLUSION: Sexual differences in occlusal
      contacts were not detected. Class I division 1 patients had the highest amount of
      occlusal contacts among all groups of malocclusion. Overjet, overbite and lower
      dental arch width were best predictors of occlusal contacts in the current
      sample.

PMID- 24939265
TI  - Overlays or ceramic fragments for tooth restoration: an analysis of fracture
      resistance.
AB  - PURPOSE: The aim of this study was to evaluate the mode of fracture and
      resistance of partial ceramic restorations of posterior teeth. MATERIALS AND
      METHODS: Thirty healthy upper premolars were selected and divided into three
      groups (n = 10): Group 1- control, healthy unrestored teeth, group 2-teeth
      restored with ceramic fragments; and group 3-teeth restored with ceramic
      overlays. The restorations were manufactured with feldspathic ceramic and
      cemented with RelyX ARC resin cement. After being stored in distilled water for 7
      days, the teeth were subjected to axial compression mechanical testing with a
      universal testing machine. Force was applied to the long axis of the tooth at a
      speed of 0.5 mm/min until fracture. The data were analyzed with one-way ANOVA and
      Tukey's test (5%). The mode of fracture was scored according to the degree of
      involvement of the tooth structure and the type of restoration. RESULTS: A
      significant difference (p < 0.05) was showed between groups 2 (1155 N) and 3
      (846.6 N), but there was no significant difference between group 1 and the other
      groups (1046 N), More extensive fractures were prevalent in the healthy teeth
      group (Group 1), which had no occlusal coverage; less severe fractures were found
      in groups 2 and 3. CONCLUSION: We conclude that teeth restored with ceramic
      fragments may offer greater resistance to fractures compared to teeth that have
      overlay restorations.

PMID- 24939266
TI  - New intracanal formulations containing doxycycline or chlorhexidine against
      Enterococcus faecalis.
AB  - The present study aims to evaluate the antimicrobial effect of two new intracanal
      preparations against E. faecalis. Thirty single-rooted human canine teeth were
      used. The crowns were removed and the roots were instrumented using a
      conventional technique. Three groups of ten teeth each were infected with 108
      CFU/ ml of E. faecalis for 21 days. The root canals were flled with new
      intracanal medications containing 3% doxycycline hydrochloride (DX) or 2%
      chlorhexidine digluconate (CHX). Ten teeth received no medication (NM)-negative
      control. Microbial samples were obtained 21 days after contamination: 14 days
      under the effect of the intracanal medications and 7 days after replacing the
      medications by BHI broth. The samples were homogenized, diluted, seeded on BHI
      agar and incubated for 48h/36 degrees C. The number of colony forming units
      (CFU/ml) was obtained and analyzed statistically. All intracanal dressings
      significantly reduced the number of bacterial cells in the root canal after 14
      days with medication. After the period with 7 days with BHI broth, the CFU counts
      of E. faecalis remained at low values. However, the NM group showed a significant
      increase of CFU in this period to similar values of the initial contamination. 3%
      doxycycline hydrochloride gel and 2% CHX gel were effective to eliminate E.
      faecalis from the root canal system.

PMID- 24939267
TI  - Structural reinforcement and sealing ability of temporary fillings in premolar
      with class II mod cavities.
AB  - AIM: To evaluate the capability to reinforce tooth structure and sealing ability
      of temporary filling materials in premolars with MOD cavities. The hypothesis is
      that temporary filling materials can concomitantly prevent microleakage and
      increase fracture resistance. MATERIALS AND METHODS: Premolars received root
      canal treatment and MOD cavities. Cavities were restored with non- eugenol cement
      (CIM), glass ionomer cement (GIC) or light curable composite (BIO). Higid and
      without restoration were controls. Materials for flexual strength and teeth were
      tested for microleakage and compressive strength. RESULTS: GIC and Higid
      presented similar compressive strength, higher than other groups. Bio and GIC
      presented similar flexural strength higher than BIO. CIM and BIO showed similar
      micro- leakage lower than GIC. CONCLUSION: The hypothesis was rejected as filling
      materials tested failed to prevent microleakage and to increase fracture
      resistance concomitantly. CLINICAL SIGNIFICANCE: GIC may be considered to restore
      weakened teeth subjected to occlusal loads. BIO and CIM are better choices to
      microleakage in teeth not subjected to mechanical stresses.

PMID- 24939268
TI  - Study of the anesthetic efficacy of inferior alveolar nerve block using articaine
      in irreversible pulpitis.
AB  - AIM: The purpose of this study was to determine the anesthetic efficacy of
      inferior alveolar nerve block (IANB) using 4% articaine and 2% lidocaine
      supplemented with buccal infiltration. MATERIALS AND METHODS: Forty five
      patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth
      were included in the study. The first group of 15 patients received 2% lidocaine
      with 1:200000 epinephrine, the second group 2% lidocaine with 1: 80,000
      epinephrine and the third group of 15 subjects received 4% articaine with
      1:100000 epinephrine. During the access cavity preparation those patients who
      complained of pain received an additional buccal infiltration. The percentage of
      subjects who got profound anesthesia and failure to achieve anesthesia were
      calculated and tabulated using a visual analog scale. RESULTS: The results
      revealed that 87% of subjects who received 4% Articaine with 1:100,000
      epinephrine got satisfactory anesthesia with inferior alveolar nerve block alone.
      Only 2 (13%) subjects received an additional buccal infiltration and none of the
      patients failed to obtain complete anesthesia with articaine. In comparison only
      40% of subjects got complete anesthesia with 2% lidocaine with 1:200000 and 60%
      with 2% lidocaine with 1:80,000. CONCLUSION: It can be concluded that 4%
      articaine can be used effectively for obtaining profound anesthesia for
      endodontic procedures in patients with irreversible pulpitis.

PMID- 24939270
TI  - The effect of 2% chlorhexidine on the bond strength of two different obturating
      materials.
AB  - The bond strength of ActiV GP and gutta-percha/AH Plus after using 2% CHX as
      final rinse was evaluated in this study. According to the final irrigation
      regimen forty roots were divided into two groups (n = 20) randomly: Group 1-5 ml
      of 17% EDTA; Group 2-5 ml of 17% EDTA followed by 5 ml of 2% chlorhexidine
      gluconate (CHX). Based on the obturation system the two groups were further
      subdivided into two subgroups (n = 10). The roots were horizontally sectioned
      from the coronal and midthird sections for measuring the push-out bond strength.
      CHX/AH Plus (2.795 +/- 0.42 MPa) and EDTA/ActiV GP (1.489 +/- 0.117 MPa) recorded
      the highest and lowest mean bond strength values respectively. It was concluded
      that when 2% CHX was used as a final irrigation rinse the bond strength of both
      gutta-percha/AH Plus and ActiV GP obturation system improved significantly.

PMID- 24939271
TI  - Knowledge of and management attitude regarding dentin hypersensitivity among
      dentists from a West African country.
AB  - AIM: The aim of the present study was to assess knowledge of, and management
      attitude of dentists regarding dentin hypersensitivity. MATERIALS AND METHODS:
      The study involved all the dentists from private and public sectors, exerting in
      Senegal. The following data were requested from the surveyed dentists using an
      anonymous questionnaire; sociodemographics (i.e. age, gender, area of activity,
      etc.) and knowledge on triggering factor, type of pain, diagnosis, preventive and
      curative procedures. RESULTS: Out of the 238 dentists who received the
      questionnaire, 68.9% returned properly filled forms. They were 116 males and 48
      females with a mean age of 41.99 +/- 8.50 years. Eighty three percent of the
      participants had a good understanding of the characteristics of pain related to
      DH and 92% recognized chemical and thermal stimuli as triggering factor while
      mechanical stimulus was not evoked. Many responders (90.9%) did not have any idea
      of the mechanism for pain transmission across the dentin. Regarding diagnosis
      technique, 68% use mechanical stimuli to elicit DH pain. Regarding management
      procedure, the use of desensitizing tooth paste is the mostly chosen option
      followed by professional topical application of fluoride. More than 1/3rd of the
      surveyed dentists confess resorting to root canal to manage DH. CONCLUSION: We
      recommend incorporation of basic science knowledge on orofacial pain and
      competencies to manage painful conditions like dentin hypersensitivity. Also,
      health regulatory institutions should make continuing dental education a
      requirement to preserve the dental licensure.

PMID- 24939269
TI  - The effect of mechanical loading on the cusp defection of premolars restored with
      direct and indirect techniques.
AB  - AIM: This study assessed the effect of fatigue load cycling on human premolars
      restored with MOD restorations (direct and indirect approaches) on cuspal
      defection, compared to intact teeth (unprepared) and unrestored teeth with an
      inlay preparation. MATERIALS AND METHODS: MOD inlay preparations were performed
      on sixty premolars with their roots embedded in acrylic resin. These teeth were
      divided into six groups (n = 10): (1) intact teeth; (2) unrestored and prepared
      teeth; (3) teeth restored with direct composite resin; (4) teeth restored with an
      indirect composite resin; (5) teeth restored with injected ceramic inlays (IPS
      Empress 2 (Ivoclar); (6) teeth restored with CAD/CAM inlays made of feldspathic
      ceramic (Vita Mark II). All of the indirect restorations were adhesively
      cemented. Strain-gauges were bonded to the buccal and lingual surfaces of the
      specimens. Compressive axial loading of 100N was applied on the occlusal face of
      the specimens to measure the cuspal deflection (microstrain) under compressive
      loading. These measurements were obtained before and after mechanical cycling (1
      Hz, 37 degrees C, 100,000x). RESULTS: Comparing the results obtained before and
      after fatiguing, the cuspal defection increased only in the CAD/CAM approach. The
      prepared tooth group had the highest cuspal defection, before and after
      mechanical cycling. CONCLUSION: The evaluated restoring approaches decrease the
      cuspal defection, consequently appear to improve the cuspal reinforcement.

PMID- 24939272
TI  - Oral impacts on daily performance in Turkish adults attending a dental school.
AB  - AIM: The purpose of this study was to evaluate oral health related quality of
      life (OHRQOL) in Turkish adults attending a dental school by using Oral Impacts
      on Daily Performance (OIDP) inventory. MATERIALS AND METHODS: This study included
      1324 patients. A modified questionnaire including sociodemographic information,
      questions about OHRQOL and OIDP inventory was prepared. The questions consisted
      of reasons and frequency for dental attendance, self-reported oral health status
      of the participants and number of natural teeth was recorded. RESULTS: The rates
      of participants experienced at least one OIDP impact was 65.2% and eating was the
      most affected item (41.6%). There was statistically significant difference
      between number of missing teeth-self reported oral health status, number of
      missing teeth-sociodemographic factors for the participants who reported at least
      one OIDP impact. CONCLUSION: This study showed that OHRQOL of Turkish adults
      attending a dental school is affected several factors including sociodemographic
      factors, regular dental visit and number of missing teeth similarly other
      societies. CLINICAL SIGNIFICANCE: OIDP inventory assesses impacts of oral health
      conditions that affect daily activities of an individual and is commonly used as
      OHRQOL indicator. Also, it is important self-report information of patients about
      changing their oral conditions and affecting daily life for the clinicians. There
      is insufficient data for OIDP inventory of Turkish dental patients. OHRQOL of
      Turkish adults was evaluated by using OIDP inventory in this study. The scale was
      found as a valid and reliable instrument for Turkish dental patients and was
      determined the relationships between this scale and several parameters.

PMID- 24939273
TI  - Evaluation and comparison of quantity and pattern of fluoride release from
      orthodontic adhesives: an in vitro study.
AB  - BACKGROUND: Orthodontic treatment has gained popularity since beginning of era of
      dentistry. Now a day, everyone is conscious about their appearance, smile and
      function. During orthodontic treatment use of brackets and adhesives are common.
      The bonding of brackets will cause demineralization which requires the
      fluoridation. So the study has been under- taken to analyze the pattern of
      fluoride release by commercially available adhesive bonding material for the
      prevention of demineralization. AIM: To evaluate and compare the clinical
      significance of quantity and pattern of fluoride release from three commercially
      available adhesives. OBJECTIVES: To assess the pattern of fluoride release and
      quantity, to reduce the decalcification of enamel around orthodontic brackets and
      bands during treatment and to prevent further use of topical fluoride both office
      and self-use agents for prevention of demineralization/for remineralization.
      MATERIALS AND METHODS: The comparison of quantity and pattern of fluoride release
      study involved commercially available bonding adhesives. They are: Group I--resin
      reinforced glass Ionomer light cure material (OrthoLC), Group II--fluoride
      releasing composite resin material (Excel) and Group III--conventional composite
      (Relay-a-bond) evaluated on 78 freshly extracted premolar teeth divided into
      three groups consisting 26 specimens in each group. The prepared specimens were
      stored in artificial saliva at 37 degrees C in an incubator for subsequent
      fluoride analysis using ORION ion selective electrode coupled with ionalyzer 901.
      Fluoride analysis made at 24 hours intervals for first 3 consecutive days and
      thereafter at the end of 10th, 17th, 24th and 31st day of bonding. The data
      obtained were tabulated and interpreted by statistical analysis using 't' test
      and one-way analysis of variance (ANOVA). OBSERVATIONS AND RESULTS: The quantity
      of fluoride release in groups I and II was significant even at the end of 31st
      day. The one-way AVOVA showed intra and inter group significance in the quantity
      of fluoride release. But group III with zero fluoride release with significant
      decalcification on enamel which requires external use of topical fluorides. The
      pattern of fluoride released was 3.06 ppm for group I and 2.01 ppm for group II
      and was declined sharply after 24 hours; and continued to decline in subsequent
      weeks. Mean quantity of fluoride release by group I was 15.08 ppm were as group
      II was 9.02 ppm over the test period of 31 days. At the end of 31st day the group
      I bonding adhesive was releasing considerable amount of fluoride compared to
      group II whereas group III was nil. At all the periods inter and intra group mean
      values were highly significant. And group III acted as base line or control group
      as it was non-fluoride releasing material. CONCLUSION: Both the fluoride
      releasing adhesive bond material are useful to reduce the risk of
      demineralization and further prevent the usage of topical fluoride application
      and reduce cost and clinical visiting time for both patient and clinician.

PMID- 24939274
TI  - Interarch tooth size relationship of Indian population: does Bolton's analysis
      apply?
AB  - BACKGROUND: Orthodontists have several methods to detect inter arch-tooth size
      discrepancies in patients presenting for orthodontic treatment. Many methods such
      as Pont's analysis, Nance and Carey's analysis, Peck and Peck ratio, Bolton's
      analysis are commonly used methods. A thorough search of literature reveals a
      paucity of reliable data on the mesiodistal dimensions of the crowns of the
      permanent dentition of Indian population. Without information about the size of
      individual tooth and groups of teeth for Indian population, it is difficult for
      the clinician to make an adequate diagnosis and treatment plan and to carry out a
      plan of therapy. AIM: To determine the size of individual permanent tooth and the
      sex differences, with tooth size ratios according to Bolton's formula and to
      evaluate the reliability of Bolton's norms (Anterior/ Posterior) in Indian
      population. MATERIALS AND METHODS: One hundred and twenty cases in which an
      excellent occlusion was naturally existent with the mean age of 22 years (18-27
      years) were selected in the study. The casts were prepared after taking alginate
      impression of maxillary and mandibular arches and pouring them immediately with
      dental stone. A sliding Digital Vernier calliper used to measure the teeth. The
      ratios of the mean of mesiodistal dimensions of types of teeth were computed.
      RESULTS: The mean overall ratio for the Indian population is found to be 92.11
      with a standard deviation of 2.12. The values ranged from 86.50-97.13 and the
      median is 92.16. The mean anterior ratio for the Indian population is found to be
      78.14 with a standard deviation of 2.59. CONCLUSION: Bolton's original data does
      not represent Indian population. In our study greater size variability was found
      in maxillary teeth as compared with mandibular teeth except mandibular first
      molar. Our study indicated that population-specific standards are necessary for
      clinical assessments. Significant differences were shown for the overall ratio
      and anterior ratio for both sexes as compared to Bolton's ratio.

PMID- 24939275
TI  - The ala-tragus line as a guide for orientation of the occlusal plane in complete
      dentures.
AB  - AIM: The use of the ala-tragus line (ATL) to orient the occlusal plane (OP) is
      controversial because there is a lack of agreement on the exact points of
      reference for this line. This study determined the relationship between the
      natural OP and ATL which was established by using the inferior border of the ala
      of the nose and (1) the superior border of the tragus (ATL1), (2) the tip (ATL2),
      and (3) the inferior border of the tragus (ATL3). MATERIALS AND METHODS: Lateral
      cephalometric radiographs were taken of each subject by a standard method and
      tracings were obtained on acetate paper to show the OP and the three ala-tragus
      lines. The relationship between the OP and each of ATL was measured for each
      subject. Mean and standard deviation values were then calculated for the
      relationship. Statistical analysis was performed using repeated measure analysis
      of variance followed by Bonferroni pairwise comparisons and Student's t-test
      (alpha = 0.05). RESULTS: Significant differences were noted between the three
      mean angles (p = 0.046). The mean angle (3.275 degrees +/- 2.54) formed by OP and
      ATL2 was significantly the smallest (p < 0.05). CONCLUSION: The ala-tragus line,
      extending from the inferior border of the ala of the nose to the tip of the
      tragus of the ear presented the closest relationship to the natural occlusal
      plane.

PMID- 24939276
TI  - Multidisciplinary treatment approach to restore deep horizontally fractured
      maxillary central incisor.
AB  - This case report demonstrates sequential periodontic, orthodontic and
      prosthodontic treatment modalities to save and restore deep horizontally
      fractured maxillary central incisor. The location of fracture was deep in the
      mucosa which reveals less than 2 mm of tooth structure to receive the crown. The
      procedures like surgical crown lengthening, endodontic post placement,
      orthodontic forced eruption, core build-up and metal-ceramic crown restoration
      were sequentially performed to conserve the fractured tooth. Forced eruption is
      preferred to surgical removal of supporting alveolar bone, since forced eruption
      preserves the biologic width, maintains esthetics, and at the same time exposes
      sound tooth structure for the placement of restorative margins.

PMID- 24939277
TI  - Clinical aspects and conservative dental management of a patient with
      fibrodysplasia ossificans progressiva.
AB  - AIM: T o present the clinical findings of a patient with fibrodysplasia
      ossificans progressiva (FOP), highlighting peculiarities of dental treatment in
      patients with this condition. BACKGROUND: FOP is a rare genetic disease
      characterized by skeletal malformations and ectopic ossifications in skeletal
      muscles, tendons, ligaments and aponeurosis. Exacerbation of these ossifications
      can be caused by dental treatment, resulting in disease progression. CASE
      DESCRIPTION: A 26-year-old male patient with a diagnosis of FOP was referred to
      our service for dental treatment. The patient presented decreased mobility in
      peripheral joints (knees and elbows), postural disability (ankylosis of the
      vertebral column), lateral deviation and shortness of the hallux, as well as
      heterotopic ossifications on the hands and back. The implementation of
      conservative dental procedures, such as oral hygiene instructions and recurrent
      topical fluoride applications, were performed in addition to endodontic and
      restorative treatments. Brief dental appointments were conducted without using
      regional anesthesia or dental dam clamps. The dental chair was positioned at 45
      degrees  to provide more comfort and to avoid exacerbating the disease. The
      patient has now completed 6 months of follow-up and is free of heterotopic
      ossifications resulting from dental treatment. CONCLUSION: The dental treatment
      modifications implemented for the present case were sufficient to establish good
      oral health and to prevent the formation of heterotopic ossifications in the
      maxillofacial region. CLINICAL SIGNIFICANCE: FOP is a rare disease dentists must
      familiarize themselves with to provide adequate, personalized treatment, which
      minimizes traumas that may exacerbate the disease.

PMID- 24939278
TI  - Uncommon true isolated macrodontia of a maxillary tooth.
AB  - Macrodontia is a rare dental anomaly which consists on the presence of any tooth
      or teeth larger than the average. In the present report the case of a child with
      an uncommon true isolated macrodontia of a maxillary central incisor is
      presented. The maxillary left central incisor was considered a macrodontic tooth
      since its mesiodistal crown dimension was 12.41 mm while the mesiodistal crown
      dimension of the maxillary right central incisor was 10.06 mm. The radiographic
      examination confirmed an enlarged maxillary left central incisor and a normal
      developing dentition. The patient did not report esthetic complaints, however,
      due the presence of anterior open bite and crowding, he was referred to
      orthodontic clinic. Thus, it must be point out the importance of the radiographic
      diagnosis to support the clinical findings, helping to plan and provide better
      treatment for the patient.

PMID- 24939279
TI  - Clear cell variant of calcifying epithelial odontogenic tumor without
      calcification: a rarity.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign, locally
      aggressive odontogenic epithelial tumor that affects the jaws. Although there are
      numerous reports on the variants of CEOT, occurrence of clear cells with complete
      absence of calcification has been a rarity. Histochemical analysis of tumor cells
      revealed glycogen granules with PAS staining, with absence of CD 1a staining in
      clear cells, while the amyloid-like deposit associated with clear cells showed
      green birefringence with Congo red. We report an unusual variant of CEOT
      occurring in a 27 years old male patient.

PMID- 24939280
TI  - Oral cytokeratins in health and disease.
AB  - The dynamics of oral mucosa is known by its inherent defensive nature. Certain
      areas demand tough shield when subjected to mechanical insults. This is met by
      structural scaffolding material referred as cytoskeleton comprised of
      intracellular protein filaments called cytokeratins in the surface squames of
      oral epithelia. They also equally contribute towards the architecture of
      odontogenic apparatus and salivary gland. Differentiation of epithelial cells
      within stratified epithelia regulates the expression of specific keratin gene.
      Any mutation in, or autoantibodies to keratins, desmosomal and cornified envelope
      proteins is translated into genetic and acquired human disorders. Sound knowledge
      of structural proteins, their expression, distribution and function plays a vital
      role in acquainting with these disorders and their application as differentiation
      markers. Thus, they form an integral aid in diagnostic pathology and may be
      instrumental in the future interventions by gene therapy. This review focuses on
      basics to current updates on oral cytokeratins with an emphasis on the genetic
      and acquired disorders of cytokeratins with oral implications.

PMID- 24939281
TI  - Patient autonomy in evidence-based dentistry.
AB  - Evidence-based dentistry is the judicious integration of scientific information
      relating to the patient's oral health and medical condition with the dentist's
      clinical expertise and the patient's own treatment needs and preferences. In this
      triad of factors, we (the dentists) are least likely to be formally trained in
      recognizing our patient's preferences. Do we understand what shapes these
      preferences?

PMID- 24939282
TI  - Characteristics of eyes with inner retinal cleavage.
AB  - PURPOSE: Inner retinal cleavage can be misdiagnosed as a glaucomatous retinal
      nerve fiber layer (RNFL) defect. This study was performed to characterize eyes
      with inner retinal cleavage. METHODS: Inner retinal cleavage is defined as the
      appearance of a dark spindle-shaped space between the nerve fibers. Patients who
      presented at our institution with inner retinal cleavage were enrolled in the
      study. All participants were evaluated by fundus examination, visual field
      testing with standard automated perimetry, and optical coherence tomography (OCT)
      imaging. RESULTS: A total of 15 eyes of 11 subjects with inner retinal cleavage
      were included in the study. The median age of the subjects was 57 years (age
      range, 30-67 years). In each case, inner retinal cleavage was located adjacent to
      retinal blood vessels. Tissue bridging the cleavage area was observed in ten
      eyes. Six eyes had epiretinal membranes (ERMs), two eyes had glaucoma, and one
      eye had ERM in addition to glaucoma. Six eyes with inner retinal cleavage without
      combined ocular abnormalities had highly myopic refractive error (-6.50 to -8.50
      diopters). Cross-sectional OCT images of the areas of inner retinal cleavage
      demonstrated defects with irregular margins and empty spaces in the inner layers
      of the retina. During the follow-up period, no eye showed changes in inner
      retinal layer cleavage or visual field sensitivity. CONCLUSIONS: Inner retinal
      cleavage was found in eyes with high myopia or ERMs. Inner retinal cleavage was
      associated with structural changes distinct from those associated with
      glaucomatous RNFL defects.

PMID- 24939283
TI  - Phospholipid-modified upconversion nanoprobe for ratiometric fluorescence
      detection and imaging of phospholipase D in cell lysate and in living cells.
AB  - Phospholipase D (PLD) is a critical component of intracellular signal
      transduction and has been implicated in many important biological processes. It
      has been observed that there are abnormalities in PLD expression in many human
      cancers, and PLD is thus recognized as a potential diagnostic biomarker as well
      as a target for drug discovery. We report for the first time a phospholipid
      modified nanoprobe for ratiometric upconversion fluorescence (UCF) sensing and
      bioimaging of PLD activity. The nanoprobe can be synthesized by a facile one-step
      self-assembly of a phospholipid monolayer composed of poly(ethylene glycol)
      (PEG)ylated phospholipid and rhodamine B-labeled phospholipid on the surface of
      upconversion nanoparticles (UCNPs) NaYF4: 20%Yb, 2%Er. The fluorescence resonance
      energy transfer (FRET) process from the UCF emission at 540 nm of the UCNPs to
      the absorbance of the rhodamine B occurs in the nanoprobe. The PLD-mediated
      hydrolysis of the phosphodiester bond makes rhodamine B apart from the UCNP
      surface, leading to the inhibition of FRET. Using the unaffected UCF emission at
      655 nm as an internal standard, the nanoprobe can be used for ratiometric UCF
      detection of PLD activity with high sensitivity and selectivity. The PLD activity
      in cell lysates is also determined by the nanoprobe, confirming that PLD activity
      in a breast cancer cell is at least 7-fold higher than in normal cell. Moreover,
      the nanoprobe has been successfully applied to monitoring PLD activity in living
      cells by UCF bioimaging. The results reveal that the nanoprobe provides a simple,
      sensitive, and robust platform for point-of-care diagnostics and drug screening
      in biomedical applications. 

PMID- 24939284
TI  - [Complications and their management after urinary diversion].
AB  - BACKGROUND: Bladder cancer is a common disease. It is predicted that 11,900 men
      and 4,500 women in Germany will be diagnosed with invasive bladder cancer in
      2014. The cystectomy, which is standard treatment in muscle-invasive bladder
      cancer, requires urinary diversion. PURPOSE: The goal of this article is to
      present the complications associated with urinary diversions and their
      management. METHODS: Based on a selective literature search in PubMed and our own
      clinical experience, the options for urinary diversion and their management are
      discussed. RESULTS: In patients treated with curative intent, orthotopic bladder
      replacement is preferred. In patients with palliative intent, incontinent
      cutaneous urinary diversion is commonly used. The present work shows the variety
      of early and late complications, peri-/postoperative mortality, and the
      management of these patients. CONCLUSION: After cystectomy, various methods for
      urinary diversion are available, which can be used in curative and/or palliative
      intent. Crucial to the success and the long-term satisfaction of the patients is
      selection of the right urinary diversion method.

PMID- 24939286
TI  - [The clinic Heilanstalt Weidenplan in Halle (Saale), origin of the German
      urology. Otto Kneise's founding of the first independent urology department in
      Germany].
AB  - The routine use of cystoscope initiated the development of the modern urology.
      Otto Kneise (1875-1953) extended the targets of cystoscopy by including
      examinations of the male bladder and prostate. He achieved the goal that
      "cystoscopy is part of general work in urology and not a pure gynecological act".
      He, thus, founded the specialty gynecological urology in the field urology, which
      prevented it from becoming an independent field. Under the leadership of Otto
      Kneise, the first independent urology department in Germany was created in the
      hospital Heilanstalt Weidenplan. 

PMID- 24939285
TI  - [First-line therapy for "high-risk prostate cancer". HELP - high intensity
      focused ultrasound (HIFU) and Eilgard in patients with high-risk prostate cancer 
      a prospective, randomized study (AP 62/10 of the AUO)].

PMID- 24939287
TI  - [Non-organic visual loss].

PMID- 24939288
TI  - Prognostic significance of dilated inferior vena cava in advanced decompensated
      heart failure.
AB  - Dilated inferior vena cava (IVC) is prevalent among patients with heart failure
      (HF), but whether its presence predicts worsening renal function (WRF) or adverse
      outcomes is unclear. This cohort study analyzed patients with left ventricular
      ejection fraction <40 % and repeated hospitalizations (>=2 times) for HF between
      August 2009 and August 2011. The study endpoints were death and HF re
      hospitalization. Among baseline parameters, IVC diameter was the most powerful
      predictor for the development of WRF (area under the curve = 0.795, cut-off value
      = 20.5 mm). During the 2-year follow-up, 36 patients (49 %) were re-hospitalized
      for HF and 14 patients (19 %) died. The event rates were significantly greater in
      the WRF group than in the non-WRF group (71 vs. 30 %, P < 0.001 for HF re
      hospitalization; 29 vs. 10 %, P = 0.03 for death). In Cox regression model, the
      risk of combined end-points was increased in patients with aging, elevated blood
      urine nitrogen, IVC >21 mm, and WRF. When adjusted for confounding factors, IVC
      >21 mm [hazard ratio (HR) 3.73, 95 % confidence interval (CI) 1.66-8.34] and WRF
      (HR 2.68, 95 % CI 1.07-6.75) were significant predictors for adverse outcomes. In
      patients with advanced decompensated HF, dilated IVC (>21 mm) predicted the
      development of WRF and could be a predictor for adverse outcomes.

PMID- 24939289
TI  - Correction of deviation of a partially resected mandible using a palatal ramp
      with the aid of a semi-adjustable articulator.
AB  - Patients having undergone hemi-mandibulectomy without further reconstruction (to
      restore the lost mandibular continuity) suffer functional limitations due to the
      resultant deviation of the segmental mandible. A palatally based guidance
      prosthesis (or palatal ramp prosthesis) is often indicated and is usually
      fabricated chairside in self-cured acrylic resin. Establishing the correct
      angulation of the slope of the palatal ramp may take several attempts before a
      satisfactory correction is achieved. This clinical report describes a laboratory
      technique in which a semi-adjustable articulator was used for fabricating the
      palatal ramp prosthesis. The patient's deviated mandibular position was
      transferred to the articulator by means of a facebow and interocclusal record.
      The angulation of the palatal ramp was then established on the semi-adjustable
      articulator and the prosthesis fabricated in heat-cured acrylic resin. Reduced
      chairside time, improved patient comfort levels, and ease in fabrication of the
      prosthesis on the semi-adjustable articulator are proposed advantages of the
      described technique. 

PMID- 24939291
TI  - Association between promoter polymorphisms of interleukin-4 gene and allergic
      rhinitis risk: a meta-analysis.
AB  - The relationship of interleukin-4 (IL-4) C-33T and C-590T (C-589T) gene
      polymorphisms with allergic rhinitis was analyzed. Data about the case control
      studies of IL-4 gene promoter polymorphisms [C-33T and C-590T (C-589T)] and their
      association with allergic diseases and correlation between serum IL-4 levels and
      allergic rhinitis were retrieved. The Stata 12.0 statistical software was applied
      to analyze the correlation between IL-4 gene polymorphisms and allergic rhinitis.
      The meta-analysis result of TT/CC genotype of -590 (-589) polymorphism showed a
      significant association with allergic diseases [OR=1.93, 95% CI (1.61-2.31),
      P=0.00]. Meta-analysis of the TT+TC versus CC genotype of IL-4 C-33/T
      polymorphism revealed significant associations with allergic diseases [OR=3.23,
      95% CI (1.13-9.25), P=0.03]. Meanwhile, there was a significant correlation
      between serum IL-4 levels and allergic rhinitis [OR=2.52, 95% CI=(1.80-3.23),
      P=0.00]. IL-4 gene -590 TT genotype may increase the risk of allergic rhinitis
      and the T allele mutation of -33 might be correlated with allergic rhinitis. 

PMID- 24939290
TI  - Effects of integrins and integrin alphavbeta3 inhibitor on angiogenesis in
      cerebral ischemic stroke.
AB  - Integrins such as alphavbeta3, alpha5beta1 play a key role in angiogenesis
      regulation, invasion and metastasis, inflammation, wound healing, etc. The up
      regulation of integrin alphavbeta3 after cerebral ischemic stroke can promote
      angiogenesis, which in turn improves functional recovery. In addition, the
      integrin alphavbeta3 inhibitor can block the blood-brain barrier (BBB) leakage
      induced by vascular endothelial growth factor (VEGF) and also can reduce
      inflammatory reaction, decrease the deposition of fibrinogen. Other studies
      showed that integrin alphavbeta3 is not essential in revascularization.
      Therefore, the effect of integrin alphavbeta3 in the whole process of brain
      function recovery merits further study. 

PMID- 24939292
TI  - Size-dependent biological effects on vascular endothelial cells induced by
      different particulate matters.
AB  - The contribution of particles to cardiovascular mortality and morbidity has been
      enlightened by epidemiologic and experimental studies. However, adverse
      biological effects of the particles with different sizes on cardiovascular cells
      have not been well recognized. In this study, sub-cultured human umbilical vein
      endothelial cells (HUVECs) were exposed to increasing concentrations of pure
      quartz particles (DQ) of three sizes (DQPM1, <1 MUm; DQPM3-5, 3-5 MUm; DQPM5, 5
      MUm) and carbon black particles of two sizes (CB0.1, <0.1 MUm; CB1, <1 MUm) for
      24 h. Cytotoxicity was estimated by measuring the activity of lactate
      dehydrogenase (LDH) and cell viability. Nitric oxide (NO) generation and
      cytokines (TNF-alpha and IL-1beta) releases were analyzed by using NO assay and
      enzyme-linked immunoabsorbent assay (ELISA), respectively. It was found that both
      particles induced adverse biological effects on HUVECs in a dose-dependent
      manner. The size of particle directly influenced the biological activity. For
      quartz, the smaller particles induced stronger cytotoxicity and higher levels of
      cytokine responses than those particles of big size. For carbon black particles,
      CB0.1 was more capable of inducing adverse responses on HUVECs than CB1 only at
      lower particle concentrations, in contrast to those at higher concentrations.
      Meanwhile, our data also revealed that quartz particles performed stronger cell
      damage and produced higher levels of TNF-alpha than carbon black particles, even
      if particles size was similar. In conclusion, particle size as well as particle
      composition should be both considered in assessing vascular endothelial cells
      injury and inflammation responses induced by particles. 

PMID- 24939293
TI  - Differential expression of alpha-adrenoceptor subtypes in rat dorsal root
      ganglion after chronic constriction injury.
AB  - mRNAs of alpha-adrenoceptor (alpha-AR) subtypes are found in neurons in dorsal
      root ganglion (DRG) and change after peripheral nerve injury. In this study, the
      distribution of alpha-AR subtype proteins was studied in L5 DRG of normal rats
      and rats with chronic constriction injury of sciatic nerve (CCI). Using
      immunofluorescence technique, it was found that alpha1A-, alpha1B-, and alpha2A
      AR proteins were expressed in large, medium, and small size neurons in normal
      DRG, and significantly increased in all size neurons 14 days after CCI. alpha1D-
      and alpha2C-AR was also expressed in all size neurons in normal DRG. However,
      alpha1D-AR was significantly increased and alpha2C-AR was decreased in small size
      neurons 14 days post CCI. alpha2B-AR neurons were not detectable in normal and
      CCI DRG. Co-expression of alpha1A- and alpha2A-AR in the same neuron was observed
      in normal DRG and increased post CCI. Collectively, these results indicated that
      there is distinct distribution of alpha-AR subtypes in DRG neurons, and the
      distribution and levels of expression of alpha-AR subtypes change differently
      after CCI. The up-regulation of alpha-AR subtypes in DRG neurons may play an
      important role in the process of generating and transmitting neuropathic pain. 

PMID- 24939294
TI  - Fucoidan induces apoptosis of HepG2 cells by down-regulating p-Stat3.
AB  - Fucoidan is one of the main bioactive components of polysaccharides. The current
      study was focused on the anti-tumor effects of fucoidan on human heptoma cell
      line HepG2 and the possible mechanisms. Fucoidan treatment resulted in cell cycle
      arrest and apoptosis of HepG2 cells in a dose-dependent manner detected by MTT
      assay, flow cytometry and fluorescent microscopy. The results of flow cytometric
      analysis revealed that fucoidan induced G2/M arrest in the cell cycle
      progression. Hoechst 33258 and Annexin V/PI staining results showed that the
      apoptotic cell number was increased, which was associated with a dose-dependent
      up-regulation of Bax and down-regulation of Bcl-2 and p-Stat3. In parallel, the
      up-regulation of p53 and the increase in reactive oxygen species were also
      observed, which may play important roles in the inhibition of HepG2 growth by
      fucoidan. In the meantime, Cyclin B1 and CDK1 were down-regulated by fucoidan
      treatment. Down-regulation of p-Stat3 by fucoidan resulted in apoptosis and an
      increase in ROS in response to fucoidan exposure. We therefore concluded that
      fucoidan induces apoptosis through the down-regulation of p-Stat3. These results
      suggest that fucoidan may be used as a novel anti-cancer agent for
      hepatocarcinoma. 

PMID- 24939295
TI  - Establishment of surfactant-associated protein A suicide gene system and analysis
      of its activity.
AB  - Alveolar epithelial type II (AT II) cells are essential for lung development and
      remodeling, as they are precursors for type I cells and also produce other non
      repair cells (fibroblasts). Progenitor cells are believed to possess capability
      of multi-potent transdifferentiation, which is closely related to the niche,
      suggesting the importance of establishment of a lung progenitor cell niche model.
      We hypothesized that pulmonary surfactant-associated protein A (SPA) suicide gene
      system would cause AT II cell to kill itself through apoptosis and leave its
      niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine
      kinase (rAAV-SPA-TK) system was established to get targeted apoptotic AT II
      cells. The apoptosis of AT II cells was detected by using MTT. The results showed
      that cloned SPA gene promoter had specific transcriptional activity in SPA high
      expression cells, and SPA high expression cells (H441) transfected with TK gene
      had higher sensitivity to ganciclovir (GCV) than SPA low expression cells (A549).
      In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system
      was observed by TUNEL. Finally, the successful packaging and application of rAAV
      SPA-TK system provide experimental basis to get specific lung progenitor cell (AT
      II) niche in vitro and in vivo. 

PMID- 24939296
TI  - Gene chip technology used in the detection of HPV infection in esophageal cancer
      of Kazakh Chinese in Xinjiang Province.
AB  - This study was aimed to screen human papillomavirus (HPV) types associated with
      esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip
      technique and study the clinical significance of this application. The DNAs were
      collected from esophageal squamous cell carcinoma tissues and healthy esophageal
      mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and
      then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens
      were further detected by the gene chip technique to screen highly pathogenic HPV
      types. After determination with nested PCR amplification with HPV MY09/11 and
      G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell
      carcinoma group and 12.12% in the healthy control group. By testing the positive
      HPV specimens from the esophageal squamous cell carcinoma group, the infection
      rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%.
      HPV16 infection may be involved in the development of esophageal squamous cell
      carcinoma in Xinjiang Hazakh adults. 

PMID- 24939298
TI  - Changes of c-fos, malondialdehyde and lactate in brain tissue after global
      cerebral ischemia under different brain temperatures.
AB  - Under global cerebral ischemia, the effect of different brain temperature on
      cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into
      normothermic (37-38 degrees C) ischemia, mild hypothermic (31-32 degrees C)
      ischemia, hyperthermic (41-42 degrees C) ischemia and sham-operated groups.
      Global cerebral ischemia was established using the Pulsinelli four-vessel
      occlusion model and brain temperature was maintained at defined level for 60 min
      after 20-min ischemia. The expression of c-fos protein and the levels of
      malondialdehyde (MDA) and lactate in brain regions were detected by
      immunochemistry and spectrophotometrical methods, respectively. C-fos positive
      neurons were found in the hippocampus and cerebral cortex after cerebral ischemia
      reperfusion. Mild hypothermia increased the expression of c-fos protein in both
      areas, whereas hyperthermia decreased the expression of c-fos protein in the
      hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when
      compared to normothermic conditions. In normothermic, mild hypothermic and
      hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were
      increased at 24, 48 and 72 h reperfusion following 20-min ischemia as compared
      with the sham-operated group (P<0.01). The levels of MDA and lactate in mild
      hypothermic group were significantly lower than those in normothermic group
      (P<0.01). It is suggested that brain temperature influences the translation of
      the immunoreactive protein product of c-fos after global cerebral ischemia, and
      MDA and lactate are also affected by hypothermia and hyperthermia. 

PMID- 24939297
TI  - SOCS3 expression correlates with severity of inflammation in mouse hepatitis
      virus strain 3-induced acute liver failure and HBV-ACLF.
AB  - Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an
      inducible endogenous negative regulator of Janus kinase/signal transducers and
      activators of transcription (JAK/STAT) pathway which is relevant in inflammatory
      response, while its functions in acute liver failure and HBV-induced acute-on
      chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study,
      we explored the role of SOCS3 in the development of mouse hepatitis virus strain
      3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral
      blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related
      gene expression was detected by real-time PCR, immunohistochemistry and Western
      blotting. The correlation between SOCS3 level and liver injury was studied. Our
      results showed that the SOCS3 expression was significantly elevated in both the
      liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic
      hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was
      increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro
      inflammatory cytokines, interleukin (IL)-1beta, IL-6, and tumor necrosis factor
      (TNF)-alpha, were also increased significantly at 72 h post-infection. There was
      a close correlation between hepatic SOCS3 level and IL-6, and the severity of
      liver injury defined by alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may
      play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and
      HBV-ACLF. 

PMID- 24939299
TI  - Expression of nerve growth factor and hypoxia inducible factor-1alpha and its
      correlation with angiogenesis in non-small cell lung cancer.
AB  - In order to investigate the expression of nerve growth factor (NGF) and hypoxia
      inducible factor-1alpha (HIF-1alpha) and its correlation with angiogenesis in non
      small cell lung cancer (NSCLC), paraffin-embedded tissue blocks from 20 patients
      with NSCLC were examined. Twenty corresponding para-cancerous lung tissue
      specimens were obtained to serve as a control. The expression of NGF, HIF-1alpha,
      and vascular endothelial growth factor (VEGF) in the NSCLC tissues was detected
      by using immunohistochemistry. The microvascular density (MVD) was determined by
      CD31 staining. The results showed that the expression levels of NGF, HIF-1alpha
      and VEGF in the NSCLC tissues were remarkably higher than those in the para
      cancerous lung tissues (P<0.05). There was significant difference in the MVD
      between the NSCLC tissues (9.19+/-1.43) and para-cancerous lung tissues (2.23+/
      1.19) (P<0.05). There were positive correlations between NGF and VEGF, between
      HIF-1alpha and VEGF, and between NGF and HIF-1alpha in NSCLC tissues, with the
      spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In
      NSCLC tissues, the MVD had a positive correlation with the three factors
      (P<0.05). Theses results suggest that NGF and HIF-1alpha are synergically
      involved in the angiogenesis of NSCLC. 

PMID- 24939300
TI  - Downregulation of LncRNAH19 and MiR-675 promotes migration and invasion of human
      hepatocellular carcinoma cells through AKT/GSK-3beta/Cdc25A signaling pathway.
AB  - LncRNAH19 has been implicated as having both oncogenic and tumor suppression
      properties in cancer. LncRNAH19 transcripts also serve as a precursor for miR
      675. However, it is unknown whether LncRNAH19 and miR-675 are involved in the
      migration and invasion of hepatocellular carcinoma (HCC) cells. The purpose of
      this study was to investigate the effect and mechanism of LncRNAH19 and miR-675
      on migration and invasion of HCC cells. The migration and invasion of HCC cells
      were measured by Transwell migration and invasion assays after transfection of
      HCC cells with miR-675 inhibitors and LncRNAH19siRNA. The levels of LncRNAH19 and
      miR-675 were detected by quantitative reverse transcriptase real-time polymerase
      chain reaction (qRT-PCR), and the protein expression of AKT, GSK-3beta and Cdc25A
      by Western blotting analysis. The expression levels of LncRNAH19 and miR-675 were
      higher in MHCC-97H cells than in L02, Huh-7 and HepG2 cells. Transwell migration
      assay revealed that the miR-675 inhibitor and LncRNAH19siRNA could significantly
      increase the migration of HCC cells (P<0.01) as compared with the control group.
      Transwell invasion assay demonstrated that the miR-675 inhibitor and
      LncRNAH19siRNA could significantly increase the invasion of HCC cells (P<0.01) as
      compared with the control group. Western blotting analysis showed that the
      expression levels of AKT and Cdc25A were significantly increased (P<0.05), and
      the expression level of GSK-3beta was significantly decreased (P<0.05) after
      treatment with miR-675 inhibitors and LncRNAH19siRNA as compared with the control
      group. These findings suggested that inhibition of LncRNAH19 and miR-675
      expression can promote migration and invasion of HCC cells via AKT/GSK
      3beta/Cdc25A signaling pathway. 

PMID- 24939301
TI  - Different responses of cell cycle between rat vascular smooth muscle cells and
      vascular endothelial cells to paclitaxel.
AB  - Although previous reports showed drug-eluting stent (DES) could effectively
      inhibit neointima formation, in-stent restenosis (ISR) remains an important
      obstacle. The purpose of this study was to investigate different effects of
      paclitaxel on proliferation and cell cycle regulators between vascular smooth
      muscle cells (VSMCs) and vascular endothelial cells (VECs) of rats in vitro. The
      cultured VSMCs and VECs of rats from the same tissues were examined by using
      immunohistochemistry, flow cytometry and Western blotting in control and
      paclitaxel-treated groups. The results showed paclitaxel could effectively
      inhibit proliferation of VSMCs and VECs. However, as compared with VECs,
      proliferation of VSMCs in paclitaxel-treated group decreased less rapidly. The
      percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase
      increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and
      PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down
      regulated as compared with VECs. It is concluded that there are significant
      differences in the expression of cell cycle regulators and proliferation rate
      between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the
      G1-S checkpoint regulated by paclitaxel may play a critical role in the
      development of complications of DES, which provides new strategies for treatments
      of ISR. 

PMID- 24939302
TI  - Involvement of VKORC1 in the inhibition of calcium oxalate crystal formation in
      HK-2 cells.
AB  - The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting
      enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of
      urolithiasis patients. This study searched for direct evidence to define the
      inhibitory activity of VKORC1 against calcium oxalate (CaOx) crystal formation.
      In the experiment of VKORC1 overexpression, HK-2 cells were transfected with the
      pFLAG-CMV-7.1-VKORC1 plasmid as a pFLAG-CMV-7.1-VKORC1 transfection group or the
      pFLAG-CMV-7.1 plasmid as a pFLAG-CMV-7.1 control group. In the experiment of
      VKORC1 knockdown, HK-2 cells were transfected with the PGPU6/GFP/Neo-VKORC1shRNA
      2 as a PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group or the PGPU6/GFP/Neo-shRNA
      NC plasmid as a PGPU6/GFP/Neo-shRNA-NC control group. The expression of VKORC1 in
      HK-2 cells was detected by real-time quantitative PCR and Western blotting. The
      CaOx crystal formation was observed under the laser-scanning confocal microscope.
      It was found that the expression levels of VKORC1 mRNA and protein were
      significantly higher in the pFLAG-CMV-7.1-VKORC1 transfection group than in the
      pFLAG-CMV-7.1 control group (P<0.01). The number of CaOx crystals in HK-2 cells
      incubated in fluorescently labeled CaOx monohydrate (COM) crystal medium for 48 h
      was 14+/-4 per field (100*) in the pFLAG-CMV-7.1-VKORC1 transfection group and
      26+/-5 per field (100*) in the pFLAG-CMV-7.1 control group respectively under the
      laser-scanning confocal microscope. The amount of CaOx crystal aggregation and
      formation in the pFLAG-CMV-7.1-VKORC1 transfection group was significantly
      reduced as compared with the pFLAG-CMV-7.1 control group (P<0.05). The expression
      levels of VKORC1 mRNA and protein were significantly lower in the PGPU6/GFP/Neo
      VKORC1shRNA-2 transfection group than in the PGPU6/GFP/Neo-shRNA-NC control group
      (P<0.05). The number of CaOx crystals in HK-2 cells incubated in fluorescently
      labeled COM crystal medium was 65+/-11 per field (100*) in the PGPU6/GFP/Neo
      VKORC1shRNA-2 transfection group and 24+/-6 per field (100*) in the PGPU6/GFP/Neo
      shRNA-NC control group respectively under the laser-scanning confocal microscope.
      The amount of CaOx crystal aggregation and formation in the PGPU6/GFP/Neo
      VKORC1shRNA-2 transfection group was significantly increased as compared with the
      PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). These findings suggested that the
      VKORC1 protein could inhibit CaOx salt crystallization, adhesion and aggregation.
      This research would help us to understand the mechanisms involving the
      interaction between crystallization and epithelial cells and the formation of
      CaOx. 

PMID- 24939304
TI  - Lateral crus graft with autologous rib cartilage for cleft lip nostril asymmetry:
      a report of 35 cases.
AB  - A surgical technique of lateral crus strut graft to correct the deformity of
      nostril contour and improve asymmetric nostril shape by autologous rib cartilage
      was reported. Thirty-five patients (20 males and 15 females), with a mean age of
      19 years (range of 16-26 years) were included in this study. All of the patients
      suffered moderate to severe unilateral cleft lip nostril deformity and underwent
      surgical technique of lateral crus strut graft by autologous rib cartilage to
      correct the asymmetric nostril contour from 2010 to 2012. The views of the
      nostril contour on both sides were reviewed and some parameters were measured at
      different time points (preoperatively, and 3 months and one year postoperatively)
      including the long axis and short axis of the nostrils. The differences in
      nostrils including long axis, short axis, elliptical area and eccentricity on the
      both sides were compared at different time points. The differences in the long
      axis and eccentricity of the nostrils on the two sides were decreased
      significantly between the preoperative view and postoperative view (P<0.05). The
      surgical technique of lateral crus graft with autologous rib cartilage is
      effective to correct the abnormal nostril contour and improve the asymmetry for
      unilateral cleft clip patients. 

PMID- 24939303
TI  - Versatility of reverse sural fasciocutaneous flap for reconstruction of distal
      lower limb soft tissue defects.
AB  - In this study we present our experiences with the reverse sural fasciocutaneous
      flap to reconstruct the distal lower limb soft tissue defects caused by traumatic
      injuries. These flap graftings were carried out from Oct. 2010 to Dec. 2012 in
      our department. The series consisted of 36 patients, including 21 men and 15
      women with an average age of 46.2 years (14-83 years) and with a medium follow-up
      period of 18 months (12-24 months). Of all the cases of acute trauma, there were
      10 cases of trauma of distal tibia, 9 cases of trauma of perimalleolus, and 17
      cases of trauma of midfoot and forefoot. Related risk factors in the patients
      were diabetes (2 cases), advanced age (>65 years, 3 cases) and cigarette smoking
      (6 cases). The reverse flow sural island flap irrigation depended on lower
      perforators of the peroneal artery. The fasciocutaneous pedicle was 3-4 cm in
      width and the anatomical structures consisted of the superficial and deep fascia,
      the sural nerve, short saphenous vein, superficial sural artery together with an
      islet of subcutaneous cellular tissue and skin. The most proximal border of the
      flap was only 1.5 cm away from the popliteal skin crease and the pivot point was
      5-7 cm above the tip of the lateral malleolus. All the flaps survived. No
      arterial crisis occurred in any case. The venous congestion occurred in 2 cases
      and got better after raising the limbs and bloodletting. Only in an old man, 1.5
      cm necrosis of distal margin of his flap occurred and finally healed after
      continuous dressing change. One-stage skin grafting was performed, and all the
      donor sites were sutured and successfully healed. It was concluded that the
      reverse sural fasciocutaneous flap is safe and reliable to extend to the proximal
      third even near the popliteal skin crease. We also concluded this flap can be
      safely and efficiently used to treat patients with large and far soft-tissue
      defects from the distal leg to the forefoot with more versatility and it is
      easier to reach the recipient sites. 

PMID- 24939305
TI  - Relationship between tyrosine phosphorylation and protein expression of insulin
      receptor and insulin resistance in gestational diabetes mellitus.
AB  - The relationship between tyrosine phosphorylation (TP) and protein expression of
      insulin receptor (InsR) and insulin resistance (IR) in patients with gestational
      diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton
      muscle tissue were determined by Western blotting and immunoprecipitation in
      women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group,
      n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting
      plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay
      and immunoradioassay. The results showed that the levels of FPG (5.61+/-0.78
      mmol/L), FINS (15.42+/-5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR)
      (1.21+/-0.52) in GDM group were significantly higher than those in normal
      pregnancy group (4.43+/-0.46 mmol/L, 10.56+/-3.07 mU/L and 0.80+/-0.31
      respectively) (P<0.01). The levels of FINS and HOMA-IR in normal pregnancy group
      were significantly higher than those in normal non-pregnant group (7.56+/-2.31
      mU/L and 0.47+/-0.26 respectively) (P<0.01). There was no significant difference
      in the InsR expression level among the three groups (P>0.05). TP of InsR with
      insulin stimulation was significantly decreased in GDM group (0.20+/-0.05) as
      compared with normal pregnancy group (0.26+/-0.06) (P<0.01). TP of InsR with
      insulin stimulation in normal pregnancy group was lower than that in normal non
      pregnant group (0.31+/-0.06) (P<0.01). TP of InsR with insulin stimulation was
      negatively related with HOMA-IR in GDM group (r=-0.525, P<0.01). There was no
      correlation between the protein expression of InsR and HOMA-IR in GDM group (r=
      0.236, P>0.05). It was suggested that there is no significant correlation between
      the protein expression of InsR in skeletal muscle and IR in GDM, but changes in
      TP of InsR are associated with IR in GDM. 

PMID- 24939306
TI  - n-Butanol extract of Rhynchosia volubilis Lour: a potent spermicidal agent In
      Vitro.
AB  - Rhynchosia volubilis Lour has been a major drug in a folk prescription for
      contraception in China, whereas its mechanism remains unknown. Its antifertility
      effects on male mice and antimicrobial activities on sexually transmitted
      infection (STI) pathogens were previously reported. This study was undertaken to
      develop the n-Butanol extract of Rhynchosia volubilis Lour (BERVL) as a
      spermicidal agent with STI prevention. The spermicidal activities of BERVL with
      different doses were assessed using selected high-motile sperms of normal human
      semen samples, and their inhibitory effects on Lactobacillus acidophilus were
      determined. The mechanism of the spermicidal activity was explored by aqueous
      Eosin Y and Hoechst 33342/PI staining. The results showed spermicidal activities
      and inhibitory effects of BERVL on Lactobacillus acidophilus were dose-dependent.
      Dose of 90 mg/mL BERVL terminated all progressive sperm motility within 2 min,
      and had slight inhibitory effect on Lactobacillus acidophilus, suggesting it was
      an effective and safe dose for contraception use. About 80% sperms exposed to
      BERVL displayed changes consistent with high permeability of head membrane. It is
      concluded that BERVL as spermicide has advantages over N-9 with strong ability to
      instantaneously kill human sperm and possesses light inhibitory effect on
      Lactobacillus acidophilus. 

PMID- 24939307
TI  - Effect of complement C1q expression on hepatic ischemia-reperfusion injury in
      rats.
AB  - The effect of the complement C1q expression on total hepatic ischemia-reperfusion
      (I/R) injury in rats was investigated. Sixty healthy male Sprague Dawley (SD)
      rats weighing 180-200 g were randomly divided into 5 groups: sham-operation group
      (S group, n=12); group of I/R for 1 h (I/R 1 h group, n=12); group of I/R for 3 h
      (I/R 3 h group, n=12); group of I/R for 6 h (I/R 6 h group, n=12); group of I/R
      for 24 h (I/R 24 h group, n=12). The hepatic I/R model of rats was established,
      and liver tissues were obtained 1 h, 3 h, 6 h and 24 h after hepatic I/R,
      respectively. Furthermore, the tissues were stained using hematoxylin-eosin, and
      the liver injuries of rats were observed using a microscope. The malondialdehyde
      (MDA) level and superoxide dismutase (SOD) activity in liver tissue were
      determined. Real-time polymerase chain reaction (PCR) and Western blotting were
      used to detect the expression levels of C1q mRNA and protein, respectively. As
      compared with the S group, the histopathological changes in I/R 1 h-24 h groups
      were gradually aggravated with the extension of I/R time. As compared with the S
      group, SOD activity and MDA content in the I/R groups were reduced and increased
      respectively with the extension of I/R time (P<0.01). Furthermore, the C1q
      expression at mRNA and protein levels in the I/R groups (especially in the I/R 3
      h group) was significantly higher than that in the S group (P<0.05). It is
      suggested that C1q expression may play a principal role in hepatic I/R injury,
      particularly at the early stage of perfusion. 

PMID- 24939308
TI  - Effect of Methyl-CpG binding domain protein 2 (MBD2) on AMD-like lesions in ApoE
      deficient mice.
AB  - The role of methyl-CpG binding domain protein 2 (MBD2) in an ApoE-deficient mouse
      model of age-related macular degeneration (AMD) was investigated. Eight-week-old
      Mbd2/ApoE double deficient (Mbd2(-/-) ApoE(-/-)) mice (n=12, 24 eyes,
      experimental group) and MBD2 (wt) ApoE(-/-) mice (n=12, 24 eyes, control group)
      were fed on Western-type diet for 4 months. The mice were sacrificed, and total
      serum cholesterol levels were analyzed and Bruch's membrane (BM) of the eyes was
      removed for ultrastructural observation by transmission electron microscopy.
      Moreover, intercellular adhesion molecule 1 (ICAM-1) immunoreactivities were
      evaluated by fluorescence microscopy in sections of the eyes in both groups for
      further understanding the function mechanism of MBD2. There was no significant
      difference in the total serum cholesterol levels between control group and
      experimental group (P>0.05). Transmission electron microscopy revealed that AMD
      like lesions, various vacuoles accumulated on BM, notable outer collagenous layer
      deposits and dilated basal infoldings of retinal pigment epithelium (RPE) were
      seen in both groups, and the BM in control group was significantly thickened as
      compared with experimental group (P<0.05). Fluorescence micrographs exhibited the
      expression of ICAM-1 in choroid was higher in control group than in experimental
      group. We are led to conclude that MBD2 gene knockout may lead to accumulation of
      more deposits on the BM and influence the pathogenesis of AMD via triggering
      endothelial activation and inflammatory response in choroid, improving
      microcirculation, and reducing lipid deposition so as to inhibit the development
      of AMD-like lesions. Our study helps to provide a new therapeutic approach for
      the clinical treatment of AMD. 

PMID- 24939309
TI  - Expression of USP15, TbetaR-I and Smad7 in psoriasis.
AB  - The deubiquitinating enzyme ubiquitin specific peptidase 15 (USP15) is regarded
      as a regulator of TGFbeta signaling pathway. This process depends on Smad7, the
      inhibitory factor of the TGFbeta signal, and type I TGFbeta receptor (TbetaR-I),
      one of the receptors of TGFbeta. The expression level of USP15 seems to play
      vital roles in the pathogenesis of many neoplasms, but so far there has been no
      report about USP15 in psoriasis. In this study, immunohistochemical staining of
      USP15, TbetaR-I and Smad7 was performed in 30 paraffin-embedded psoriasis
      specimens and 10 normal specimens to investigate the expression of USP15, TbetaR
      I and Smad7 in psoriasis and to explore the relevance among them. And USP15 small
      interfering RNA (USP15 siRNA) was used to transfect Hacat cells to detect the
      mRNA expression of TbetaR-I and Smad7. Of 30 cases of psoriasis in active stage,
      28, 24 and 26 cases were positive for USP15, TbetaR-I and Smad7 staining,
      respectively. The positive rates of USP15 and Smad7 were significantly higher in
      psoriasis specimens than in normal skin specimens (44.1%+/-26.0% vs. 6.1%+/-6.6%,
      47.2%+/-27.1% vs. 6.6%+/-7.1%), and positive rate of TbetaR-I (20.3%+/-22.2%) in
      psoriasis was lower than that in normal skin specimens (46.7%+/-18.2%). There was
      a significant positive correlation between USP15 and Smad7 expression, and
      significant negative correlations between USP15 and TbetaR-expression, an I d
      between TbetaR- and Smad7 expression I in psoriasis. After transfection of USP15
      siRNA in Hacat cells, the expression of TbetaR-mRNA was up I -regulated and that
      of Smad7 was down-regulated. It is concluded that USP15 may play a role in the
      pathogenesis of psoriasis through regulating the TbetaR-I/Smad7 pathway and there
      may be other cell signaling pathways interacting with USP15 to take part in the
      development of psoriasis. 

PMID- 24939310
TI  - Efficacy of solution form of ethylenediaminetetraacetic acid on removing smear
      layer of root canal at different exposure time In Vitro.
AB  - This study was aimed to evaluate the effectiveness of solution form of 17%
      ethylenediaminetetraacetic acid (EDTA) on removing smear layer of root canals at
      different exposure time periods and to provide scientific basis for EDTA as a
      choice of root canal irrigation in clinical practice. Twenty-five single-rooted
      teeth were randomly divided into 5 groups: control group (group A) was given 2.5%
      NaOCl, and 4 experimental groups were given 2.5% NaOCl and 17% EDTA, including
      groups B, C, D and E with exposure time of 1, 3, 5 and 7 min, respectively. After
      preparation of the root canals, the teeth were split along their longitudinal
      axis, and the root sections were examined under scanning electron microscope for
      evaluation of smear layer removal and erosion on the surface of the root canal
      walls. The specimens in group B showed presence of smear layer on the walls of
      the root canal with no statistical difference from that in group A (P>0.05). In
      groups C and D, partial removal of smear layer was obtained, and there was no
      significant difference between the two groups (P>0.05), but there was significant
      difference in removal of smear layer between group C and group B (P<0.05). Root
      canal walls in group E specimens showed almost complete removal of smear layer,
      and the removal of smear layer was significantly different from that in group D
      (P<0.01). There was no significant change in the structure of the surface of root
      canal for each sample. It was concluded that combined irrigation with 17% EDTA
      and 2.5% NaOCl could remove the smear layer with no significant alteration in
      dentinal structure when the chelating agent was applied for 7 min. At 3 and 5 min
      of application, partial removal of smear layer was observed and at 1 min
      negligible removal of smear layer was achieved. 

PMID- 24939311
TI  - Three-dimensional localization of impacted canines and root resorption assessment
      using cone beam computed tomography.
AB  - The purpose of this study was to develop a new way to localize the impacted
      canines from three dimensions and to investigate the root resorption of the
      adjacent teeth by using cone beam computed tomography (CBCT). Forty-six patients
      undergoing orthodontic treatments and having impacted canines in Tongji Hospital
      were examined. The images of CBCT scans were obtained from KaVo 3D exam vision.
      Angular and linear measurements of the cusp tip and root apex according to the
      three planes (mid-sagittal, occlusal and frontal) have been taken using the
      cephalometric tool of the InVivo Dental Anatomage Version 5.1.10. The
      measurements of the angular and linear coordinates of the maxillary and
      mandibular canines were obtained. Using this technique the operators could
      envision the location of the impacted canine according to the three clinical
      planes. Adjacent teeth root resorption of 28.26 % was in the upper lateral
      incisors while 17.39% in upper central incisors, but no lower root resorption was
      found in our samples. Accurate and reliable localization of the impacted canines
      could be obtained from the novel analysis system, which offers a better surgical
      and orthodontic treatment for the patients with impacted canines. 

PMID- 24939312
TI  - Development of a liquid chromatography-tandem mass spectrometry method for
      determination of butoconazole nitrate in human plasma and its application to a
      pharmacokinetic study.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      and validated for the determination of butoconazole in human plasma. Human plasma
      samples of 0.2 MUL were pretreated by a single step protein precipitation
      procedure and analyzed using a high performance liquid chromatography (HPLC)
      electrospray tandem mass spectrometer system. The compounds were eluted
      isocratically on an Inertsil ODS-SP column (100 mm*2.1 mm, 3 MUm), ionized using
      a positive ion atmospheric pressure electrospray ionization source and analyzed
      using multiple reaction monitoring (MRM) mode. The ion transitions monitored were
      m/z 412.8->165.1 for butoconazole and m/z 453.4->230.3 for the internal standard.
      The chromatographic run time was 3.5 min per injection, with retention time of
      2.47 min and 2.15 min for butoconazole and repaglinide, respectively. The method
      was validated to be linear over the range of 20 to 8000 pg/mL (r>0.999) by using
      a weighted (1/x(2)) quadratic regression. The mean recovery rate was more than
      86.7%, and the intra- and inter-day precision of the quality control samples
      (QCs) was less than 8.3% and the accuracy ranged from 96.0% to 110.2%, which
      indicated that the quantitative method was reliable and accurate. The method is
      simple, rapid, and has been applied successfully to a pharmacokinetics study of
      butoconazole nitrate suppositories in healthy Chinese females. 

PMID- 24939313
TI  - Psychological intervention for postpartum depression.
AB  - The postpartum depression outcome and the effect of psychological intervention
      were studied in order to reduce the occurrence and development of the postpartum
      depression. A survey of 4000 women within 4-6 weeks postpartum in 80 communities
      in Shenzhen, China was performed using random cluster sampling method. By
      employing Edinburgh Postnatal Depression Scale (EPDS) as a screening tool, the
      positive women (defined as EPDS >=10) were randomly divided into intervention
      group and control group at a ratio of 1:2. The women in the intervention group
      were treated by means of mailing postpartum depression prevention and treatment
      knowledge manual, face-to-face counseling, and telephone psychological counseling
      interventions aiming at individual risk factors, while those in the control group
      were treated with conventional methods. EPDS scores were assessed in these two
      groups again at 6th month postpartum. Totally, 3907 valid questionnaires were
      obtained. All the 771 positive women were divided into two groups: 257 in the
      intervention group, and 514 in the control group. At 6th month postpartum, the
      EPDS scores in the intervention group were decreased significantly, from baseline
      stage (12.84+/-3.02) to end stage (3.05+/-2.93), while EPDS scores in the control
      group were reduced from 12.44+/-2.78 to 6.94+/-4.02. There were significant
      differences in the EPDS scores at end stage between the two groups (t=13.059,
      P<0.001). Psychological intervention can reduce postpartum depression, with
      better maternal compliance. It is feasible and necessary to establish postpartum
      depression screening and psychological intervention model in community-hospital
      and include the postpartum depression screening, intervention, and follow-up into
      the conventional healthcare. 

PMID- 24939315
TI  - Efficacy of Jian'ganle () versus Hugan Pian (), glucuronolactone and reduced
      glutathione in prevention of antituberculosis drug-induced liver injury.
AB  - Evidence-based medicine is advocated by WHO and adopted by developed countries
      for many years. In China, however, the selection of essential medicine and
      various medical insurance reimbursement schemes medicine is usually based on
      experts' experience of prescription practice which is under heavy critics
      resulting from the lack of related comparative efficacy and evidence-based
      research. The efficacy of Jian'ganle in prevention of drug-induced liver injury
      (DILI) caused by antituberculotics was evaluated in this study by comparison with
      Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for
      relevant sectors such as Ministry for Human Resources and Social Security of the
      People's Republic of China and National Health and Family Planning Commission of
      the People's Republic of China to select and renew the Essential Medicine List
      (EML), the new rural cooperative medical scheme in China (NRCMS) list or the
      reimbursement list of industrial injury insurance. A total of 189 patients with
      initial pulmonary tuberculosis were divided into four groups who took
      antituberculotics combined with Jian'ganle, Hugan Pian, glucuronolactone and
      reduced glutathione respectively. Their liver function profile including alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL),
      direct bilirubin (DBIL), total protein (TP), albumin (A) and globulin (G) were
      detected at admission as baseline and after treatment. The Jian'ganle group was
      compared with the three others by chi-square tests. In an aspect of maintaining
      bilirubin indexes normal, Jian'ganle was more efficacious than glucuronolactone.
      And Jian'ganle had a little more efficacy than reduced glutathione to maintain
      protein indexes normal as well. And the therapeutic regimen of antituberculotics
      combined with Jian'ganle was the best in treating tuberculosis and preventing
      DILI at the same time. The study showed that among the four hepatinicas which
      demonstrated similar prevention of DILI caused by antituberculotics, Jian'ganle
      has more advantages over the three others to some extent, which provides a
      reliable basis for health sectors to select and renew the EML, NRCMS List or the
      reimbursement list of industrial injury insurance. 

PMID- 24939314
TI  - Influencing factors of mental health of medical students in China.
AB  - This study investigated the mental health status of medical students in China,
      and analyzed the influencing factors in order to provide evidence for mental
      health education for medical students. A stratified cluster sampling method was
      used to recruit medical students from Huazhong University of Science and
      Technology, China. The questionnaire survey on general information and Symptom
      Checklist 90 (SCL-90) were used for investigation and analysis. The results
      showed among the 1137 valid questionnaires, 278 (24.45%) participants had SCL-90
      score >= 160. The top three mental problems of medical students were obsessive
      compulsive disorder, interpersonal sensitivity and depression in terms of the
      factor score >= 2.5 and the number of participants who reflected on the diseases.
      The third-year medical students had the worst mental health status, and fifth
      year medical students had the best mental health status. Students from rural area
      had more psychological problems than those from urban area; furthermore, students
      with high professional satisfaction, those who were the single child of the
      family, non-poor students, and those whose parents had high education level had
      better mental health status. It was concluded that the mental health of medical
      students is not optimistic in China. Medical students have some mental health
      problems of different degrees. Factors that influence the mental health of
      medical students include academic pressure, professional satisfaction level and
      family environment. 

PMID- 24939316
TI  - Is nationwide special campaign on antibiotic stewardship program effective on
      ameliorating irrational antibiotic use in China? Study on the antibiotic use of
      specialized hospitals in China in 2011-2012.
AB  - With dwindling number of new antibiotics and inappropriate use of antibiotics,
      the emergence and spread of antibiotics resistance occurs commonly in healthcare
      institutions worldwide. In China, antibiotics are commonly over prescribed and
      misused. This study is to assess the effect of the nationwide special campaign on
      antibiotic stewardship program (ASP) at specialized hospitals in China by
      investigating prescription information from 2011 to 2012. Data on the hospital
      consumption and prescription of systemic antibiotics were obtained from four
      specialized hospitals, including maternity, children's, stomatological and cancer
      hospitals. Systematic random sampling was used to select outpatient prescriptions
      and inpatient cases. A total of 105 specialized hospitals in 2011 and 121
      specialized hospitals in 2012 were analysed. The defined daily doses (DDDs) per
      100 inpatient days, the percentage of antibiotic use in outpatient prescriptions,
      and the percentage of antibiotic use in inpatient cases were used as measurements
      of antibiotic use. The overall antibiotic use density in the selected hospitals
      decreased between 2011 and 2012 from 39.37 to 26.54 DDD/100 inpatient days
      (P<0.001). The percentage of antibiotic use in outpatient prescriptions (range:
      24.12%-18.71%, P=0.109) and inpatient cases (64.85%-60.10%, P=0.006) also
      decreased within the two years. Significant changes were observed among regions
      and different hospitals within the two years. And antibiotic consumption was
      correlated with the type and size of specialized hospital in 2012, but not with
      the regions. This analysis of antibiotic consumption of specialized hospitals
      allows relevant comparisons for benchmarking and shows that national ASP has
      improved antibiotic rational use in China. The data will assist policymakers in
      formulating effective strategies to decrease antibiotic overuse and identify
      areas that require further work.

PMID- 24939319
TI  - Isolated fallopian tube torsion with partial hydrosalpinx in a premenarcheal
      girl: a case report.
AB  - INTRODUCTION: Isolated fallopian tube torsion as a complication of a preexisting
      hydrosalpinx is a rare finding in pediatric patients. The obvious rarity of this
      condition, its subtle diagnostic features and dissonant previous reporting about
      the appropriate therapeutic approach according to age, future conception capacity
      and potential complications of possible pregnancies make the decision about which
      surgical approach to use very difficult. In this report, we describe the case of
      a patient with such a presentation and review the literature. Very few similar
      reports of neosalpingostomy in pediatric patients have been published to date.
      CASE PRESENTATION: In our present report, we describe the case of an 11-year-old
      Caucasian prepubertal girl who presented to our hospital with complaints of
      abdominal pain in the right lower quadrant, nausea and vomiting. The diagnostic
      workup led us to conclude that she had a torsion of the right ovary, which was
      cystically altered. Exploratory surgery revealed a partial hydrosalpinx and
      consecutive isolated torsion of the fimbrial part. The proximal isthmic part of
      the fallopian tube was intact and vital. Restorative surgery was performed to
      create a neosalpingostomy on the viable isthmic part of the tube and remove the
      cystic and twisted fimbrial and infundibular parts. CONCLUSION: The surgical
      procedure described in this report is technically simple and feasible, but leaves
      doubts about the final outcome.

PMID- 24939320
TI  - Interleukin-1beta-immunoreactive neurons in the hippocampus and paraventricular
      nucleus of the hypothalamus after stress stimulation in aged versus adult rats.
AB  - It is believed that the impact of stress on interleukin-1beta (IL-1beta) depends
      on the ontogenetic age. This study examines the influence of acute or chronic
      exposure to forced-swim (FS) stress or high-light open-field (HL-OF) stimulation
      on the expression of IL-1beta. Double immunofluorescence staining was used to
      reveal the density of IL-1beta/NeuN (NeuN is a neuronal nuclear marker)
      immunoreactive (-ir) cells in the hippocampal subfields CA1 and CA3, dentate
      gyrus (DG), and paraventricular nucleus (PVN) of the hypothalamus. Adult
      postnatal day 90 (P90) and aged (P720) rats were used in this experiment. The
      data showed a significant increase in the density of IL-1beta/NeuN-ir cells in
      the CA1, CA3, DG, and PVN in P720 nonstressed rats in relation to P90 control
      animals. Neither FS nor HL-OF acute stimulation caused alteration in the density
      of IL-1beta-ir neurons in any of the investigated structures in P90 and P720 rats
      in comparison with control groups. However, chronic FS caused a significant
      increase in CA3 and DG of P720 rats, and chronic HL-OF led to a significant
      increase in the density of IL-1beta-ir neurons in the PVN of P90 rats and in all
      hippocampal subfields of P720 animals. These results indicate that chronic HL-OF
      stimulation is a factor that induces changes in the number of IL-1beta-ir neurons
      in the PVN of adult rats, whereas both chronic FS and HL-OF are aggravating
      factors for the hippocampus of aged (P720) animals.

PMID- 24939317
TI  - Therapeutic suppression of premature termination codons: mechanisms and clinical
      considerations (review).
AB  - An estimated one-third of genetic disorders are the result of mutations that
      generate premature termination codons (PTCs) within protein coding genes. These
      disorders are phenotypically diverse and consist of diseases that affect both
      young and old individuals. Various small molecules have been identified that are
      capable of modulating the efficiency of translation termination, including select
      antibiotics of the aminoglycoside family and multiple novel synthetic molecules,
      including PTC124. Several of these agents have proved their effectiveness at
      promoting nonsense suppression in preclinical animal models, as well as in
      clinical trials. In addition, it has recently been shown that box H/ACA RNA
      guided peudouridylation, when directed to modify PTCs, can also promote nonsense
      suppression. In this review, we summarize our current understanding of eukaryotic
      translation termination and discuss various methods for promoting the read
      through of disease-causing PTCs, as well as the current obstacles that stand in
      the way of using the discussed agents broadly in clinical practice. 

PMID- 24939321
TI  - Serum and urine galactomannan testing for screening in patients with
      hematological malignancies.
AB  - Testing for serum galactomannan (GM) has been established as an important method
      for diagnosing invasive aspergillosis (IA); however, limited data exist regarding
      the application of urine GM testing. The objective of this study was to evaluate
      the performance of GM screening of urine specimens and to compare results with
      serum GM. The study was performed between July 2012 and March 2013 in adult
      patients with underlying hematological malignancies who were hospitalized at the
      Medical University of Graz, Austria. Serum and urine screening samples were
      collected and tested twice weekly (always on the same day). In total, 242 serum
      samples and a similar number of urine samples were collected from 75 patients. A
      total of 21/242 (8.7%) serum samples from 13 patients were GM positive.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value using a 0.1 optical density index cutoff for urine samples (compared with
      same-day serum results) were as follows: 47.6%, 86%, 24.4%, and 94.5%,
      respectively. In 8/10 patients with probable IA, at least one positive GM result
      was found with this cutoff. After calculating clinical performance of the urine
      GM test, we found that sensitivity increased to 71.4% and specificity to 88.2%.
      Spearman-Rho correlation analysis revealed a significant positive correlation
      between serum and urine samples (P < 0.001; rho = 0.252). In conclusion, GM
      detection in urine might be a promising method for IA screening. However, further
      studies are needed. 

PMID- 24939322
TI  - Caffeine as an indicator of estrogenic activity in source water.
AB  - Caffeine has already been used as an indicator of anthropogenic impacts,
      especially the ones related to the disposal of sewage in water bodies. In this
      work, the presence of caffeine has been correlated with the estrogenic activity
      of water samples measured using the BLYES assay. After testing 96 surface water
      samples, it was concluded that caffeine can be used to prioritize samples to be
      tested for estrogenic activity in water quality programs evaluating emerging
      contaminants with endocrine disruptor activity.

PMID- 24939323
TI  - Synthesis and antioxidant activity of 3-(Pyridin-2-ylmethyl)-1,3
      thiazinan(thiazolidin)-4-ones.
AB  - The antioxidant properties of two series of thiazolidinones and thiazinanones
      were reported. The novel six-membered thiazinanones were synthesized from the
      efficient multicomponent reaction of 2-picolylamine (2-aminomethylpyridine),
      arenaldehydes, and the 3-mercaptopropionic acid in moderate to excellent yields.
      These novel compounds were fully identified and characterized by NMR and GC-MS
      techniques. In vitro antioxidant activities of all compounds were evaluated by
      2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6
      sulfonic acid (ABTS) tests. The antioxidant assays of thiobarbituric acid
      reactive species and total thiol content levels in the cerebral cortex and liver
      of rats were also performed. Thiazinanone 5a showed the best radical scavenging
      activity in DPPH and ABTS tests, as well as reduced lipid peroxidation and
      increased total thiol group in biological systems. Altogether, the results may be
      considered a good starting point for the discovery of a new radical scavenger. 

PMID- 24939324
TI  - Regadenoson for myocardial perfusion imaging: Is it safe?

PMID- 24939325
TI  - Mixed chimerism and graft loss in pediatric recipients of an alemtuzumab-based
      reduced-intensity conditioning regimen for non-malignant disease.
AB  - BACKGROUND: Reduced-intensity conditioning (RIC) regimens can mitigate the
      toxicity of hematopoietic cell transplantation (HCT) in children with non
      malignant diseases, but are associated with increased risk for post-transplant
      mixed donor/recipient chimerism (MC) and/or graft loss (GL). Intervention with
      donor lymphocytes or stem cell boosts (DLI/boost) may be necessary, but there is
      limited information about timing and results of intervention. PROCEDURE: We
      retrospectively evaluated 31 consecutive pediatric recipients of an alemtuzumab
      based RIC HCT at the Children's Hospital of Philadelphia from May 2007 to
      December 2012 to determine the incidence of MC, GL, and use of DLI/boost. All
      patients received alemtuzumab with either fludarabine (150 mg/m(2) )/melphalan
      (140 mg/m(2) ) (n = 30) or fludarabine/busulfan (n = 1), and unmanipulated marrow
      grafts from related (48%) or matched unrelated (52%) donors. RESULTS: Of
      surviving patients, 67% and 44% displayed MC and MC with <=80% donor contribution
      (MC <= 80%), respectively. Rates of MC, MC <= 80%, DLI/boost, and GL were
      significantly higher in recipients of proximal/intermediate (100%, 73%, 46%, and
      46%, respectively) compared to distal alemtuzumab (44%, 25%, 6%, and 6%,
      respectively). Event-free and overall survival was significantly lower in HLH
      compared with non-HLH patients. Twenty percent of patients required DLI/boost,
      and DLI/boost did not affect the incidence of GL. CONCLUSIONS: RIC with
      proximal/intermediate alemtuzumab is associated with high rates of MC, need for
      DLI/boost, and GL.

PMID- 24939326
TI  - The impact of obesity on adult tracheostomy complication rate.
AB  - OBJECTIVES/HYPOTHESIS: Prospectively compare tracheostomy-related complications
      in obese patients with complications in nonobese patients. STUDY DESIGN:
      Prospective cohort study. METHODS: Adult patients undergoing tracheostomy were
      studied. Patients who had a prior tracheostomy were excluded. Complications were
      classified as intraoperative, early (within the first 2 weeks), or late. RESULTS:
      A total of 151 patients met inclusion/exclusion criteria. Fifty-five percent of
      obese patients experienced at least one tracheostomy-related complication; 19.5%
      of the control group had a complication. Mean procedure duration for patients
      with body mass index < 30 was 24.74 minutes and for obese patients was 46.17
      minutes. There was a statistically significant effect of body mass index on
      complication rate (P < .0001) and on procedure duration (P < .0001). The
      relationships between body mass index and intraoperative complications (P = .027)
      and early postoperative complications (P = .001) were significant. CONCLUSIONS:
      The tracheostomy-related complication rate is significantly higher for obese
      patients, especially for body mass index >= 35, especially in the intraoperative
      and early postoperative time periods. Procedure duration is significantly longer
      in obese patients.

PMID- 24939327
TI  - People come into our lives for a reason.

PMID- 24939328
TI  - Interdisciplinary preceptor teams to improve the clinical nurse leader student
      experience.
AB  - The Clinical Nurse Leader (CNL) role was introduced by the American Association
      of Colleges of Nursing (AACN) in 2003 (AACN, 2003). There are now over 2,500
      certified CNLs in the United States. Still some areas of the country have no CNLs
      in practice; this was true of north central Texas until May 2010 when Texas
      Christian University (TCU) had its first graduating class. Lack of CNLs to serve
      as preceptors for the practicum courses in the CNL program was one concern,
      although AACN does offer options when CNLs are not available. TCU's CNL teaching
      team developed the interdisciplinary preceptor team (IPT) model to strengthen the
      practicum component of CNL education at TCU. One advantage of the IPT model is
      the match it provides with several CNL competencies: lateral integration of care
      via interdisciplinary teams, member and leader of health care teams, skillful
      communication within teams, and implementation of an interdisciplinary approach
      to safe, quality, patient care. Components of the IPT model are discussed with
      specific information about preceptor selection, team development, and examples of
      feedback from preceptors and students. 

PMID- 24939329
TI  - Implementing AACN's recommendations for environmental sustainability in colleges
      of nursing: from concept to impact.
AB  - In 2011, the American Association of Colleges of Nursing (AACN) released a
      guidance report titled Toward an Environmentally Sustainable Academic Enterprise:
      An AACN Guide for Nursing Education. The report was developed in response to a
      vivid slide presentation at an AACN meeting depicting the deleterious public and
      environmental health effects of global industrialization. Following the
      presentation, AACN members capitalized on the opportunity to provide national
      leadership to U.S. colleges of nursing in regard to environmental sustainability
      and stewardship. This article summarizes key features of the AACN plan and
      outlines one college's multifaceted implementation plan. The goal of the
      implementation plan was to translate the AACN recommendations from concept into
      college-specific actions. Specific steps taken by the college included the
      following: (a) increasing student and faculty awareness, (b) greening business
      operations, (c) increased participation in media events, (d) leveraging the
      impact of national sustainability initiatives, and (e) enhancing curricula at the
      undergraduate and graduate levels. Through this work, the college achieved not
      only a higher standard of sustainability within its own walls but also a richer
      appreciation of the importance of educating nurses as future stewards in an
      environmentally sustainable health care system. 

PMID- 24939331
TI  - Faculty to faculty incivility: experiences of novice nurse faculty in academia.
AB  - Academic incivility creates a challenging work environment for nursing faculty.
      Understanding the concept of faculty-to-faculty incivility may enlighten faculty
      regarding appropriate interpersonal relationships, assist in alleviating uncivil
      behavior, and improve the likelihood that faculty will remain in nursing
      education, potentially easing the current nursing faculty shortage. The primary
      purpose of this study was to describe novice nurse faculty members' lived
      experiences of faculty-to-faculty incivility. A second purpose was to describe
      and understand how incivility influences faculty decision to remain in nursing
      academia. A hermeneutical phenomenological approach was selected to uncover the
      lived experience. A purposive sample of eight novice nursing faculty, those with
      less than 5 years of experience, was obtained via e-mail recruitment from mid
      Atlantic college Web sites. Five themes and 7 subthemes emerged. Among the
      findings were sensing rejection, employing behaviors to cope with uncivil
      colleagues, sensing others wanted novice faculty to fail, sensing a
      possessiveness of territory from senior faculty, and struggling with the decision
      to remain in the faculty position. This study is significant in that
      understanding of faculty-to-faculty incivility adds insight and an increased
      sensitivity related to uncivil interactions and may contribute to the design of
      evidence-based interventions supporting increased collegiality that fosters an
      environment conducive for the recruitment and retention of faculty. 

PMID- 24939330
TI  - Transition to academic nurse educator: a survey exploring readiness, confidence,
      and locus of control.
AB  - The purpose of this study was to describe nurse transition to the role of
      academic nurse educator and to investigate the resources and barriers that nurses
      experience during this career transition, specifically the relationships among
      levels of readiness, confidence, personal control, support, decision
      independence, general self-esteem, and work locus of control. A convenience
      sample of registered nurses in the United States (N = 541) who hold current full
      time employment at an accredited nursing program granting baccalaureate or higher
      degrees was utilized. Subjects were recruited via electronic mail and answered an
      on-line survey. Pearson product-moment correlation and multivariate analysis of
      variance were used for statistical calculations. Results indicated significant,
      positive relationships among all the variables except readiness and personal
      control (p = .01). Significant differences were found in amount of time that
      nurses were in the role of academic nurse educator and the demographic variables
      of number of children, marital status, and highest degree held. The results of
      this study provide evidence to support and enhance processes to develop and
      retain nurse academicians, to promote excellence in the academic nurse educator
      role, and to advance the science and practice of the profession. 

PMID- 24939332
TI  - Global trends and issues in APN practice: engage in the change.
AB  - The advanced practice nursing (APN) movement represents a global vision with
      similar issues facing APNs across dissimilar countries, disparate political
      structures, and diverse cultures. As APNs work toward independent practice, they
      face external challenges from medicine and internal barriers within the domain of
      nursing. This paper presents reflections on the major practice issues raised at
      the 7th International Nurse Practitioner/Advanced Practice Nursing Network
      Conference, a subgroup of the International Council on Nursing (ICN), in London
      in August, 2012. Major issues addressed at the conference included independent
      practice, barriers to practice, educational standards, and the APN role in
      research and evidence-based practice. APNs are best placed to provide and direct
      an advanced level of quality healthcare. APNs must develop consensus models and
      present as a more unified force in the quest for independent practice. 

PMID- 24939333
TI  - Using a strengths model to build an on-line nursing education program.
AB  - The on-line environment is the new frontier for academia struggling to define its
      place in the evolving economy. A concern is how to engage students who maximize
      their on-line experience and graduate in a timely manner. A strengths model was
      used as the basis for development of an on-line doctoral nursing program. Upon
      entering the program, students were given a strengths assessment that focused
      both students and faculty on the positive attributes students were bringing to
      their doctoral studies. A positive feedback methodology using on-line discussions
      in each course was used to support the identified strengths. The optimal picture
      of a successful entering doctoral student appears to be a person whose top five
      strengths are learner, achiever, input, connectedness and responsibility. A
      strengths model promotes a positive learning environment and supports a teacher
      learner dynamic where faculty members are encouraged to focus on the students'
      strengths rather than their challenges. 

PMID- 24939334
TI  - Responding to the call for globalization in nursing education: the implementation
      of the transatlantic double-degree program.
AB  - Increased demand for nurses worldwide has highlighted the need for a flexible
      nursing workforce eligible for licensure in multiple countries. Nursing's
      curricular innovation mirrors the call for reform within higher education
      including globalization of curricula (E. J. S. Hovenga, 2004; D. Nayyar, 2008; B.
      J. G. Wood, S. M. Tapsall, & G. N. Soutar, 2005), increased opportunities for
      student mobility exchanges, dialogue between different academic traditions, and
      mutual understanding and transparency between universities (J. Gonzalez & R.
      Wagenaar, 2005). The European Union (EU) and United States have combined efforts
      to achieve these objectives by creating the Atlantis program in 2007 (U.S.
      Department of Education, 2011). This article describes experiences of four
      nursing programs participating in an Atlantis project to develop a double-degree
      baccalaureate program for undergraduate nursing students. Early learnings include
      increasing awareness and appreciation of essential curricular and performance
      competencies of the baccalaureate-prepared professional nurse. Challenges include
      language competency; variations in curriculum, cultural norms, student
      expectations, and learning assessment; and philosophical differences regarding
      first-level professional nurse preparation as specialist versus generalist. The
      Transatlantic Double Degree program has successfully implemented the double
      degree program. Members have gained valuable insights into key issues surrounding
      the creation of a more uniform, yet flexible, educational standard between our
      countries. 

PMID- 24939335
TI  - Clarifying concepts: cultural humility or competency.
AB  - Cultural competency in the delivery of health care to diverse population groups
      has become an urgent need in the United States. Yet, despite the incorporation of
      cultural competency education into nursing curricula, inequities in health care
      remain. The purpose of this mixed-method study was to identify if differences in
      perceptions of cultural competence were present in senior nursing students (N =
      11) before and after cultural immersion experiences on an Indian reservation.
      Preimmersion results revealed that the majority considered themselves culturally
      competent, whereas after immersion, there was a downward shift in scores.
      Triangulation of the quantitative results alongside a hermeneutic
      phenomenological analysis of the students' reflective journals revealed a
      paradox. Students perceived themselves as culturally competent, yet their
      journals demonstrated many negative stereotypes. Three common themes emerged:
      seeing with closed eyes, seeing through a fused horizon, and disruption to
      reshaping. These combined results revealed the misperceptions regarding the
      concept of cultural competency. Efforts must be made in nursing education to
      teach students the importance of adopting an ethic of cultural humility, where we
      emphasize attentive listening and openness to other cultures, and stress the
      importance of self-reflection and self-critique in our interactions with others. 

PMID- 24939336
TI  - The use of high-fidelity simulation to teach cultural competence in the nursing
      curriculum.
AB  - The United States population is undergoing a major demographic shift, by the year
      2050, it is predicted that minority populations will constitute half of the
      general population. This evolving population change is significant due to the
      overwhelming burden of disease that minorities face in the nation. Cultural
      competence training is currently being used to prepare practitioners to provide
      care to a diverse population in an effort to eliminate health disparities. With
      the increasing demands of the nursing curriculum and the limited time frame to
      prepare competent clinicians, the search continues for innovative strategies that
      will produce culturally competent providers. Patient simulation is a technique
      that replicates real-world scenarios in a controlled and nonthreatening
      environment. However, despite the legal and moral obligations that nurses have to
      provide culturally competent care, a lack of evidence exists regarding how to
      properly integrate simulation methods for cultural competence training into the
      nursing curriculum. In the nursing curriculum, patient simulation has been used
      mainly to teach the biomedical aspects of care with less focus on the
      psychological, cultural, and environmental context. The potential exists for the
      use of high-fidelity patient simulation as an effective teaching strategy for
      cultural competence training. 

PMID- 24939337
TI  - Minimal changes and missed opportunities: a decade look at nurse practitioners in
      the lower Mississippi River Delta states.
AB  - The U.S. southern region has one of most socioeconomically deprived and poorest
      health care outcomes in the county. The aims of this study were to determine
      changes of nurse practitioners (NPs) and their practice in lower Mississippi
      River Delta over the past decade and to examine differences of NPs' employment in
      health professional storage areas (HPSAs) and rural areas. A nonexperimental
      quantitative survey technique was used in the years 2000 and 2010. Other data
      sources included Health Resources and Services Administration that identified
      HPSA and the U.S. Census Bureau used to distinguish urban and rural areas. NPs
      are younger, and more are graduates of master's and doctorate degrees, but they
      are not reflective of the race they serve. Approximately, 25% of NPs worked in
      HPSA, and 50% worked in the rural area both in 2000 and in 2010. This proportion
      has remained blatantly steady during the past decade. Employment in rural health
      centers and family practice as a specialty declined; however, self-employment was
      on the rise. Nursing schools and health care institutions should be collaborating
      to develop plans and implementation strategies to recruit and retain NPs in the
      Mississippi River Delta rural and HPSAs. 

PMID- 24939338
TI  - Re-envisioning clinical education for nurse practitioner programs: themes from a
      national leaders' dialogue.
AB  - As the need for primary care providers increases, nursing education programs face
      significant challenges to meet future workforce needs. A more resource-efficient
      approach for the clinical education of nurse practitioner students is needed. A
      think tank involving 20 thought leaders representing multiple disciplines was
      convened to discuss this issue. This article presents seven themes that emerged
      from this national leaders' dialog: academic practice co-design, standardized
      preclinical preparation, standardized student assessment, entrustable
      professional activities, immersive clinical experiences, interprofessional
      education for team-based care, and innovative education practices. 

PMID- 24939339
TI  - Antioxidant activity and protein-polyphenol interactions in a pomegranate (Punica
      granatum L.) yogurt.
AB  - Pomegranate juice (PGJ) is rich in phenolics which are potent antioxidants but
      also prone to interact with proteins. A yogurt rich in PGJ (40%) made from arils
      was elaborated (PGY) to determine the antioxidant activity and to estimate the
      phenolics-proteins interaction during 28 days of cold storage. Juice, yogurts,
      and protein-free permeates were analyzed for phenolic composition. Yogurt
      fermentation modified the anthocyanin profile of the initial PGJ, especially the
      content in cyanidin-3-O-glucoside. During storage, individual anthocyanin content
      in PGY decreased but it did not modify yogurt color. The analysis of permeates
      revealed that the degree of phenol-protein interaction depends on the type of
      phenolic, ellagic acid and dephinidin-3,5-O-diglucoside being the least bound
      phenolic compounds. The presence of PGJ in yogurt enhanced radical scavenging
      performance, whereas all the observed ferric reducing power ability of PGY was
      strictly due to the PGJ present. The 84.73% of total anthocyanins remained bound
      to proteins at the first day of storage and 90.06% after 28 days of cold storage,
      revealing the high affinity of anthocyanins for milk proteins. 

PMID- 24939340
TI  - MSM: a new flexible framework for Multimodal Surface Matching.
AB  - Surface-based cortical registration methods that are driven by geometrical
      features, such as folding, provide sub-optimal alignment of many functional areas
      due to variable correlation between cortical folding patterns and function. This
      has led to the proposal of new registration methods using features derived from
      functional and diffusion imaging. However, as yet there is no consensus over the
      best set of features for optimal alignment of brain function. In this paper we
      demonstrate the utility of a new Multimodal Surface Matching (MSM) algorithm
      capable of driving alignment using a wide variety of descriptors of brain
      architecture, function and connectivity. The versatility of the framework
      originates from adapting the discrete Markov Random Field (MRF) registration
      method to surface alignment. This has the benefit of being very flexible in the
      choice of a similarity measure and relatively insensitive to local minima. The
      method offers significant flexibility in the choice of feature set, and we
      demonstrate the advantages of this by performing registrations using univariate
      descriptors of surface curvature and myelination, multivariate feature sets
      derived from resting fMRI, and multimodal descriptors of surface curvature and
      myelination. We compare the results with two state of the art surface
      registration methods that use geometric features: FreeSurfer and Spherical
      Demons. In the future, the MSM technique will allow explorations into the best
      combinations of features and alignment strategies for inter-subject alignment of
      cortical functional areas for a wide range of neuroimaging data sets. 

PMID- 24939341
TI  - Physiological and analytical validations of fecal steroid hormone measures in
      black howler monkeys.
AB  - The measurement of hormones in fecal samples allows for the noninvasive
      assessment of the endocrine status of free-ranging primates. However, procedures
      and techniques for hormone analysis in feces must be validated, both analytically
      and physiologically. Few studies have addressed the endocrinology of black howler
      monkeys (Alouatta pigra). Due to its conservation status, direct handling of
      individuals from this species and invasive sample collection are highly
      regulated, and therefore traditional methods for the validation of hormone
      assays, such as pharmacological challenges, are not allowed. As a consequence,
      sometimes studies of the fecal hormones of free-ranging black howler monkeys do
      not report physiological validations and therefore the biological reliability of
      such measurements cannot be assessed. In order to stimulate future research with
      this species, the present study aimed at providing methodological bases for fecal
      endocrine monitoring. Specifically, we compared the validity of two immunoassays
      (radioimmunoassays, RIA; solid-phase chemiluminescent enzyme immunoassay, SPCEI)
      performed with commercial kits to measure cortisol, testosterone, estradiol, and
      progesterone; and demonstrate how the physiological functions of these steroid
      hormones can be determined through non-pharmacological validations. We found no
      differences between the analytical validity of RIA and SPCEI assays to measure
      cortisol and testosterone, whereas for estradiol and progesterone RIA showed
      better results. Concerning the physiological validation of our assays, we
      demonstrated that: (1) comparisons between pre- and post-stress situations may be
      used to assess cortisol response, (2) comparisons between females and males may
      be used to assess variation in testosterone levels, and (3) comparisons between
      pregnant and non-pregnant females may be used to determine variation in estradiol
      and progesterone activity. The analytical and physiological validations that we
      performed demonstrate that there are currently commercial kits that allow for
      correct endocrine monitoring of this species, and that there are non
      pharmacological alternatives to assess the biological validity of hormone
      measurements. 

PMID- 24939342
TI  - Concise multigram-scale synthesis of push-pull tricyanofuran-based hemicyanines
      with giant second-order nonlinearity: an alternative for electro-optic materials.
AB  - Highly stable and highly soluble push-pull heptamethine hemicyanines based on the
      tricyanofuran electron-accepting group can be prepared on a 15 g scale. The
      compounds display giant second-order nonlinear figure of merit, MUbeta of up to
      31,000*10(-48) esu, and lead to a poled material with a second-order nonlinear
      response, r33 of 90 pm V(-1) at 1.06 MUm.

PMID- 24939343
TI  - John Biggers.

PMID- 24939344
TI  - Reflections of one man's life in Nature: Professor John D Biggers, DSc, PhD.

PMID- 24939345
TI  - On John Biggers.

PMID- 24939346
TI  - A tribute to John Biggers: on The Politics of Memory.

PMID- 24939347
TI  - A brief history of the development of the KSOM family of media.

PMID- 24939348
TI  - Non-invasive prediction of development of hepatocellular carcinoma using
      transient elastography in patients with chronic liver disease.
AB  - Prognosis of patients with chronic liver disease is determined by the extent and
      progression of liver fibrosis, which may ultimately lead to hepatocellular
      carcinoma (HCC). Liver biopsy (LB) is regarded as the gold standard to estimate
      the extent of liver fibrosis. However, because LB has several limitations, the
      foremost being its invasiveness, several non-invasive methods for assessing liver
      fibrosis have been proposed. Of these, transient elastography (TE) provides an
      accurate representation of the extent of liver fibrosis. Furthermore, recent
      studies have focused on the usefulness of TE for assessing the risk of HCC
      development and HCC recurrence after curative treatment, and developed novel
      models to calculate the risk of HCC development based on TE findings. These
      issues are discussed in this expert review. 

PMID- 24939350
TI  - Survey burden, response rates, and the tragedy of the commons.

PMID- 24939349
TI  - Describing prescription opioid adherence among individuals with chronic pain
      using urine drug testing.
AB  - Adherence monitoring for prescription opioid use is a clinical imperative for
      individuals prescribed opioids for chronic pain. Urine drug testing (UDT)
      provides objective evidence for prescription opioid adherence, as recommended by
      national guidelines to be part of adherence monitoring. The aim of this study was
      to describe prescription opioid adherence using UDT results in chronic pain
      patients and to examine the association between demographic characteristics and
      adherence to their prescribed opiate regimens. We used a retrospective chart
      review of 120 consecutive patients at an urban pain management clinic. Data
      collected included UDT results, pain level, and demographic characteristics.
      Descriptive and correlational statistics were used for data analysis. About 54%
      of the individuals appeared nonadherent to their prescribed opiate regimen as
      defined by absence or inappropriate level of prescribed controlled medication,
      presence of additional nonprescribed controlled substance(s), presence of illicit
      substance(s), or presence of adulterant in the urine sample. Of the participants,
      23% had absence of one or more of their prescribed controlled medications and
      12.5% had presence of one or more other opioids. Marijuana was the main illicit
      substance used (24.2%), followed by cocaine (11.7%). Patients' age, pain level,
      sex, ethnicity, and injury compensation were not associated with UDT results. UDT
      results could be useful to educate and guide patients on the proper use of
      controlled medications. Results from UDT are highly contextual and easily
      misinterpreted, requiring comparison with a variety of clinical indicators over
      time before deciding if there is adherence to a prescribed opiate regimen for
      individuals with chronic pain. 

PMID- 24939351
TI  - Long-term outcomes of a remedial education program for doctors with clinical
      performance deficits.
AB  - INTRODUCTION: Medical regulatory authorities need reliable methods of assessing
      and remediating doctors where there are concerns over competence. There's a small
      but growing literature describing remediation programs and documenting their
      effectiveness. This article adds to that literature by describing a program
      associated with the Medical Council of New Zealand (MCNZ) and reporting outcomes
      for 24 consecutive doctors required to undergo remediation. METHODS: Over the 18
      month period covered in this study, 24 doctors were required by the MCNZ to enter
      remediation after a performance assessment. The data set used in this study was
      drawn from these 24 consecutive cases and included the nature of concerns,
      severity of concerns, results of remediation and outcome of a second assessment
      when such an assessment was ordered. RESULTS: Of 24 doctors who underwent initial
      assessment, 5 failed to engage with remediation and withdrew from clinical work.
      A 12-month education remediation program was completed by all remaining 19
      doctors. Of these, 13 were considered to be practicing at an acceptable standard
      at the end of remediation on the basis of sequential supervisor reports. Six
      doctors were required to have a second performance assessment. Of these, only 1
      was considered to be functioning at an acceptable standard. Concurrent health
      concerns were common among this cohort of doctors. DISCUSSION: Seventy-five
      percent of doctors who entered remedial education were considered to be
      practicing at an acceptable standard at the end of remediation. This accords well
      with international data. A small number of doctors appear to be unresponsive to
      remediation.

PMID- 24939352
TI  - All for one and one for all: understanding health professionals' experience in
      individual versus collaborative online learning.
AB  - INTRODUCTION: Computer-supported collaborative learning (CSCL) may facilitate
      continuing interprofessional education while overcoming barriers of time and
      place for busy health care professionals. The purpose of this study was to
      understand the experiences, advantages, and challenges of group versus individual
      online learning. METHODS: Fifteen multidisciplinary health professionals
      participated in a 12-week online course on either diabetes or traumatic brain
      injury. This consisted of background e-modules and a longitudinal build-a-case
      exercise, done either individually or as a group. Focus group sessions exploring
      participants' experiences after course completion and at 4 months were conducted,
      transcribed, and analyzed for recurring themes. Participant reflection homework
      and video-recorded group sessions were used for triangulation of results.
      RESULTS: Individual learners appreciated the flexibility and control, but
      experienced decreased motivation. Group learners appreciated the immediate
      feedback from their co-learners and felt social pressure to come to the weekly
      sessions prepared but expressed challenges in determining group goal-setting for
      the session. Both groups felt they learned about interprofessional roles;
      however, group learners described a richer learning experience and understanding
      of interprofessional roles through the online collaboration exercise. The intense
      resources necessary for interprofessional CSCL, including time, faculty
      development, and technological issues, are described. DISCUSSION: CSCL is a
      valuable educational strategy in online learning. While individual online
      learning may be better suited for short and simple educational interventions such
      as knowledge acquisition, CSCL seems to allow for richer and deeper learning in
      complex and interprofessional educational experiences. However, strategies,
      resources, and faculty development required to enhance CSCL need to be addressed
      carefully.

PMID- 24939353
TI  - Professionalism and maintenance of certification: using vignettes describing
      interpersonal dilemmas to stimulate reflection and learning.
AB  - INTRODUCTION: Physicians do not always agree on "rules" governing behavior in
      professionally challenging situations. Little is known about contextual factors
      that influence physician approaches in these situations. We explored the
      individual-, social-, and societal-level factors that physicians consider when
      responding to 2 common professional dilemmas. We were particularly interested in
      knowing the extent to which physicians engage in self-reflection as a result of
      responding to the vignettes. METHODS: A cross-sectional Web-based survey was sent
      to a random sample of 396 physicians, prompting them to respond to scripted
      professional dilemmas. RESULTS: A total of 120 physicians responded, yielding a
      response rate of 32.6%. Physicians responded to these dilemmas in highly variable
      ways, negotiating a complex array of contextual factors in their decisions.
      Interacting factors involving individual-level physician (eg, worry, guilt),
      patient (eg, nature of medical condition or relationship with patient), and
      social/societal (eg, policy, what peers or colleagues do) were important drivers
      in physician responses. Qualitative analysis revealed that several interacting
      themes guide physician approaches to professional dilemmas: patient welfare;
      types of patients; political, ethical, or legal issues; guiding principles;
      values; rules; and habits. DISCUSSION: Physicians negotiate a complex set of
      individual-, social-, and societal-level factors in response to professional
      dilemmas. This finding has important implications for the promotion and
      assessment of professional behavior in practicing physicians. Reflecting on
      scenarios may be an opportunity for physicians to learn about how and why they
      make decisions in difficult situations.

PMID- 24939354
TI  - Using a commitment to change tool for evaluation and planning of a global
      competency-based curriculum in orthogeriatrics.
AB  - INTRODUCTION: Measuring the outcomes of educational activities at the performance
      level is a challenge for all medical educators. This study reports retrospective
      outcomes data from the administration of a commitment to change (CTC) at
      orthogeriatrics courses and how the findings were used for curriculum
      improvement. METHODS: During 2010-2012, a CTC questionnaire was administered at 8
      educational courses attended by 513 orthopedic and trauma surgeons and medicine
      physicians in 5 countries. The CTC asked if physicians intended to change
      anything in their clinical practice as a result of participating and to list
      their specific changes. A 3-month follow-up was conducted to assess the status of
      intended changes and identify barriers to implementation. RESULTS: Two hundred
      seventy-six (54%) of the 513 course participants and faculty reported at least 1
      intended change in their clinical practice (485 specific changes overall). The
      intended changes were quantified and analyzed further based on 10 competencies
      for orthogeriatrics. Follow-up responses were received for N = 150 (31%) of the
      intended changes. Of these changes, 24% were fully implemented, 51% were
      partially implemented, and 25% were not implemented. The main barriers to
      implementation were categorized as "ongoing process (needs more time)" and
      "requires more discussion, collaboration, or support." DISCUSSION: CTC is an
      effective tool for self-reported measurement of outcomes of educational
      activities at the performance level with orthopedic surgeons and an
      interprofessional audience. Analysis based on a framework of competencies enables
      curriculum improvement by identifying content that could be adjusted and new
      materials to address the issues and barriers that were reported.

PMID- 24939356
TI  - Recycling the bi-cycle concept.

PMID- 24939355
TI  - Self-directed study using MP3 players to improve auscultation proficiency of
      physicians: a randomized, controlled trial.
AB  - INTRODUCTION: Studies of physicians at all levels of training demonstrate
      significant deficiencies in cardiac auscultation skills. The best instructional
      methods to augment these skills are not known. METHODS: This study was a
      randomized, controlled trial of 83 noncardiologist volunteers exposed to a 12
      week lower cognitive load self-study group using MP3 players containing heart
      sound audio files compared to a group receiving a 1-time 1-hour higher cognitive
      load multimedia lecture using the same audio files. The primary outcome measure
      was change in 15-question posttest score at 4 and 12 weeks as compared to pretest
      on recognition of identical audio files introduced during training. In the self
      study group, the association of total exposure and deliberate practice effort
      (estimated by standard deviation of files played/mean) to improvement in test
      score was measured as a secondary end point. RESULTS: Self-study group
      participants improved as compared to pretest by 4.42 +/- 3.41 answers correct at
      12 weeks (5.09-9.51 correct, p < .001), while those exposed to the multimedia
      lecture improved by an average of 1.13 +/- 3.2 answers correct (4.48-5.61
      correct, p = .03). In the self-study arm, improvement in the posttest was
      positively associated with both total exposure (beta = 0.55, p < .001) and
      deliberate practice score (beta = 0.31, p = .02). DISCUSSION: A lower cognitive
      load self-study of audio files improved recognition of cardiac sounds, as
      compared to multimedia lecture, and deliberate practice strategies improved study
      efficiency. More investigation is needed to assess transfer of learning to a
      wider range of cardiac sounds in both simulated and clinical environments.

PMID- 24939357
TI  - The bi-cycle concept--relating continuing education directly to patient care.
AB  - This excerpted article originally appeared in Stearns NS, Getchell ME, Gold RK.
      Continuing Medical Education in Community Hospitals: A Manual for Program
      Development. Boston: Postgraduate Medical Institute, 1971, 88-96; and was
      published by the Massachusetts Medical Society, as a supplement to The New
      England Journal of Medicine, Vol. 284; No. 20; May 20, 1971. 

PMID- 24939358
TI  - Intimate partner violence among rural South African men: alcohol use, sexual
      decision-making, and partner communication.
AB  - Nearly one-third of South African men report enacting intimate partner violence.
      Beyond the direct health consequences for women, intimate partner violence is
      also linked to varied risk behaviours among men who enact it, including alcohol
      abuse, risky sex, and poor healthcare uptake. Little is known about how to reduce
      violence perpetration among men. We conducted retrospective, in-depth interviews
      with men (n = 53) who participated in a rural South African programme that
      targeted masculinities, HIV risk, and intimate partner violence. We conducted
      computer-assisted thematic qualitative coding alongside a simple rubric to
      understand how the programme may lead to changes in men's use of intimate partner
      violence. Many men described new patterns of reduced alcohol intake and improved
      partner communication, allowing them to respond in ways that did not lead to the
      escalation of violence. Sexual decision-making changed via reduced sexual
      entitlement and increased mutuality about whether to have sex. Men articulated
      the intertwined nature of each of these topics, suggesting that a syndemic lens
      may be useful for understanding intimate partner violence. These data suggest
      that alcohol and sexual relationship skills may be useful levers for future
      violence prevention efforts, and that intimate partner violence may be a
      tractable issue as men learn new skills for enacting masculinities in their
      household and in intimate relationships.

PMID- 24939360
TI  - Evidence that glycine induces lipid peroxidation and decreases glutathione
      concentrations in rat cerebellum.
AB  - Patients with non-ketotic hyperglycinemia (NKH) present severe neurological
      symptoms and brain abnormalities involving cerebellum. Although the
      pathomechanisms underlying the cerebellum damage have not been studied, high
      tissue levels of glycine (GLY), the biochemical hallmark of this disorder have
      been suggested to contribute to the neuropathology of this disease. We
      investigated the in vitro effects of GLY on important parameters of oxidative
      stress and energy metabolism in cerebellum of 30-day-old rats. Our results show
      that GLY increased 2',7'-dichlorofluorescin oxidation, suggesting that reactive
      species production are augmented by GLY in the cerebellum. However, hydrogen
      peroxide generation was not altered by GLY. GLY also increased thiobarbituric
      acid-reactive substances (TBA-RS) levels and reduced the glutathione (GSH)
      content, indicating that this amino acid provokes lipid oxidative damage and
      compromises the non-enzymatic antioxidant defenses, respectively, in cerebellum.
      The antioxidants melatonin and trolox (the hydrosoluble analog of vitamin E)
      prevented the GLY-induced increase of TBA-RS and decrease of GSH in cerebellum,
      indicating the involvement of hydroxyl and peroxyl radicals in these effects. The
      NMDA receptor antagonist MK-801 also attenuated GLY-induced decrease of GSH,
      suggesting that this effect is mediated through NMDA receptor. In contrast, GLY
      did not alter the protein carbonyl formation and total and protein-bound
      sulfhydryl group content, as well as catalase and superoxide dismutase
      activities. Furthermore, GLY did not alter the activities of the respiratory
      chain complexes and creatine kinase. Our present data indicate that oxidative
      stress elicited by GLY in vitro may be a potential pathomechanism involved in the
      cerebellar dysfunction observed in NKH. 

PMID- 24939359
TI  - Mitochondrial epigenetics in bone remodeling during hyperhomocysteinemia.
AB  - Increased levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is
      an independent risk factor of various diseases. Clinical studies report that
      people born with severe HHcy develop skeletal malformations with weaker bone.
      Studies also report that altered mitochondrial dynamics and altered epigenetics
      contribute to weaker bones and bone diseases. Although Hcy-induced mitochondrial
      dysfunction has been shown to affect bone metabolism, the role of mitochondrial
      epigenetics (mito-epigenetics) has not been studied in bones. The epigenetics in
      mitochondria is interesting as the mitochondrial genome size is small (16 kb)
      with fewer CpG, and without histones and introns. Recently, fascinating works on
      epigenetics along with the discovery of histone-like proteins in mitochondria are
      giving exciting areas for novel studies on mitochondria epigenetics. There are
      mutual cause and effect relationships between bone, mitochondria, Hcy, and
      epigenetics, but unfortunately, studies are lacking that describe the involvement
      of all these together in bone disease progression. This review describes the
      reciprocal relationships and mechanisms of Hcy-bone-mitochondria-epigenetics
      along with a short discussion of techniques which could be employed to assess Hcy
      induced anomaly in bone, mediated through alterations in mito-epigenetics. 

PMID- 24939361
TI  - The PPARbeta/delta agonist GW0742 modulates signaling pathways associated with
      cardiac myocyte growth via a non-genomic redox mechanism.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors that belong to the nuclear hormone receptor superfamily and
      appear to have beneficial effects in the cardiovascular system. PPARbeta/delta
      has been shown previously to exert an inhibitory effect on cardiac myocyte
      hypertrophy in vivo and in vitro although the exact mechanism is not fully clear
      yet. The principal signaling pathways that have been involved in triggering
      cardiac hypertrophic response are mitogen-activated protein kinases (MAPKs) and
      PI3K/Akt cascades. In this study, we sought to evaluate the potential effects
      evoked by PPARbeta/delta activation on signaling pathways that are implicated in
      cardiac myocyte growth responses. The selective PPARbeta/delta agonist GW0742
      attenuated ERK1/2 and Akt phosphorylation that was stimulated by growth promoting
      agonists (phenylephrine, insulin or IGF-1). This effect was not reversed by the
      specific PPARbeta/delta antagonist, GSK0660, but was inhibited by vanadate, a
      potent protein tyrosine phosphatase inhibitor. In addition, GW0742 prevented the
      oxidation and inactivation of PTEN supporting further the notion that its
      inhibitory action on the agonist-induced kinase phosphorylation is mediated by
      the modulation of phosphatase activity. Furthermore, GW0742 abolished the agonist
      induced intracellular generation of reactive oxygen species, independently of
      PPARbeta/delta activation. Our data reveals a new non-genomic mechanism of
      GW0742, which ameliorates the generation of reactive oxygen species and
      attenuates ERK1/2 and PI3K/Akt signaling, with implications in the regulation of
      cardiac hypertrophic response. 

PMID- 24939362
TI  - Biphasic response of checkpoint control proteins in hyperoxia: exposure to lower
      levels of oxygen induces genome maintenance genes in experimental baboon BPD.
AB  - Breathing high concentrations of oxygen (hyperoxia) causes lung injury and is
      associated with lung diseases such as bronchopulmonary dysplasia (BPD),
      respiratory distress syndrome and persistent pulmonary hypertension of the
      newborns. Hyperoxia (95-100 %O2) causes DNA damage and growth arrest of lung
      cells and consequently cells die by apoptosis or necrosis. Although supplemental
      oxygen therapy is clinically important, the level and duration of hyperoxic
      exposure that would allow lung cells to reenter the cell cycle remains unclear.
      We hypothesized that cells exposed to lower concentrations of hyperoxia will
      retain the capacity to enter cell cycle when recovered in room air. We employed
      varying concentrations of oxygen (21-95 %) to determine the response of lung
      cells to hyperoxia. Our results indicate that cells were growth arrested and
      failed to reenter the cell cycle when exposed to greater than 60 % oxygen. Cell
      cycle checkpoint proteins were increased in a biphasic manner, increasing until
      70 % oxygen, but declined in greater than 90 % oxygen. Microarray analysis shows
      that there is significant decrease in the abundance of Cdks 6-8 and
      retinoblastoma protein (Rb), p107 and p130 in exposure to 90 % oxygen for 48 h.
      We further tested the effect of clinically relevant as needed oxygen [(pro-re
      nata (prn)] in premature infant (125-days and 140-days) baboon model of BPD. The
      microarray results show that 6 or 14d PRN oxygen-exposed animals had induced
      expression of chromosomal maintenance genes (MCMs), genes related to anti
      inflammation, proliferation, and differentiation. 

PMID- 24939363
TI  - Inhibition of acid-sensing ion channel 1a in hepatic stellate cells attenuates
      PDGF-induced activation of HSCs through MAPK pathway.
AB  - Acid-sensing ion channels (ASICs), a group of Na(+)-selective and Ca(2+)-permeant
      ligand-gated cation channels, can be transiently activated by extracellular acid.
      Among seven subunits of ASICs, acid-sensing ion channel 1a (ASIC1a), which is
      responsible for Ca(2+) transportation, is elevated in response to inflammation,
      tumor, and ischemic injury in central nervous system and non-neuronal tissues. In
      this study, we demonstrated for the first time the presence of ASIC1a in rat
      liver and hepatic stellate cells (HSCs). Furthermore, the expression of ASIC1a
      was increased in primary HSCs and liver tissues of CCl4-treated rats, suggesting
      that ASIC1a may play certain role in liver fibrosis. Interestingly, we identified
      that the level of ASIC1a was significantly elevated in response to platelet
      derived growth factor (PDGF) induction in a time- and dose-dependent manner. It
      was also established that Ca(2+)-transporting ASIC1a was involved in acid-induced
      injury of different cell types. Moreover, inhibition or silencing of ASIC1a was
      able to inhibit PDGF-induced pro-fibrogenic effects of activated rat HSCs,
      including cell activation, de novo synthesis of extracellular matrix components
      through mitogen-activated protein kinase signaling pathway. Collectively, our
      studies identified that ASIC1a was expressed in rat liver and HSCs and provided a
      strong evidence for the involvement of the ASIC1a in the progression of hepatic
      fibrosis. 

PMID- 24939365
TI  - Assessment of children exposed to adult pulmonary tuberculosis in Cali, Colombia.
AB  - BACKGROUND: There is a lack of uniform criteria for the diagnosis and management
      of tuberculosis (TB) in children in Cali, Colombia. Addressing TB in children is
      a challenge in this setting, under both programmatic and research conditions.
      OBJECTIVES: To facilitate the diagnostic assessment of TB in a paediatric cohort
      of TB household contacts. METHODS: A diagnostic and management algorithm (DMA)
      was used to assess children exposed to adult TB cases, according to clinical and
      epidemiological findings and under programmatic conditions. On the basis of
      diagnostic tests, cases were classified as TB exposure, TB infection, suspected
      TB, possible TB or confirmed TB and then submitted to a management plan. This was
      a prospective pilot study nested within a national cohort study of the
      transmission dynamics of Mycobacterium tuberculosis, undertaken in Colombia
      during 2005-2008. RESULTS: During 24 months of follow-up, 54 of 217 children met
      the criteria for assessment by DMA, 18 of whom (33%) were considered to be TB
      incident cases (new TB cases among household contacts). The main clinical
      findings were failure to thrive and cough lasting >21 days. Only one case was
      smear-positive and culture-confirmed TB. TB treatment was given to 16 children
      and they demonstrated clinical and radiographic resolution at follow-up.
      Conducting the study under programmatic conditions demonstrated barriers to
      accessing competent radiological evaluation, correct interpretation of the
      tuberculin skin test, and proper specimen collection. CONCLUSION: Structured
      assessment using DMA facilitated the detection of incident TB cases. The study
      identified potential barriers to addressing childhood TB in Cali.

PMID- 24939366
TI  - Usefulness of partial uncinectomy in patients with localized maxillary sinus
      pathology.
AB  - PURPOSE: Conventional total uncinectomy may be unnecessary in localized maxillary
      sinus lesion. Partial removal of the uncinate process and middle meatal
      antrostomy would be sufficient to eradicate the pathological condition.
      Therefore, we aimed to evaluate the efficacy of partial uncinectomy versus total
      removal of the uncinate process in patients with localized maxillary sinus
      disease. METHODS: In total, 25 patients were assigned randomly to partial and
      total uncinectomy groups. Preoperative computed tomography established that all
      patients had localized pathology in the maxillary sinus. The lower half of the
      uncinate process was removed in the partial uncinectomy group, while the total
      uncinectomy group underwent the conventional surgery. Time required for the
      uncinectomy, healing period for the uncinectomy site, incidence of lamina
      papyracea or nasolacrimal duct injury, obstruction or stenosis of the frontal
      recess, and incidence of synechia formation in the middle meatus were compared
      between the groups. RESULTS: All patients completed the follow-up and were
      included in the analysis. Surgical indications included chronic maxillary
      sinusitis, fungal sinusitis, antrochoanal polyp, and odontogenic sinusitis.
      Operation durations and healing periods were significantly shorter in the partial
      uncinectomy group. One patient had a minor injury to the lamina papyracea and two
      patients showed partial synechia formations in the total uncinectomy group.
      However, other parameters did not differ significantly between the groups.
      CONCLUSIONS: Partial uncinectomy may be useful in patients with pathological
      conditions confined to the maxillary sinus. Shorter operation duration, more
      rapid healing, and lower incidence of complications are advantages over a
      conventional total uncinectomy.

PMID- 24939367
TI  - Pattern recognition algorithm reveals how birds evolve individual egg pattern
      signatures.
AB  - Pattern-based identity signatures are commonplace in the animal kingdom, but how
      they are recognized is poorly understood. Here we develop a computer vision tool
      for analysing visual patterns, NATUREPATTERNMATCH, which breaks new ground by
      mimicking visual and cognitive processes known to be involved in recognition
      tasks. We apply this tool to a long-standing question about the evolution of
      recognizable signatures. The common cuckoo (Cuculus canorus) is a notorious cheat
      that sneaks its mimetic eggs into nests of other species. Can host birds fight
      back against cuckoo forgery by evolving highly recognizable signatures? Using
      NATUREPATTERNMATCH, we show that hosts subjected to the best cuckoo mimicry have
      evolved the most recognizable egg pattern signatures. Theory predicts that
      effective pattern signatures should be simultaneously replicable, distinctive and
      complex. However, our results reveal that recognizable signatures need not
      incorporate all three of these features. Moreover, different hosts have evolved
      effective signatures in diverse ways. 

PMID- 24939364
TI  - Arthroscopy after locked plating of proximal humeral fractures: implant removal,
      capsular release, and intra-articular findings.
AB  - PURPOSE: The purpose of this study was to determine the outcomes of arthroscopy
      after proximal humeral plating and the occurrence of concomitant pathology and
      avascular necrosis. METHODS: Forty-five patients (28 women; median age, 58.5
      years [range, 30 to 82 years]) underwent arthroscopies of 46 shoulders because of
      unsatisfactory results after locked plating of proximal humeral fractures. They
      were prospectively followed up for 3, 12, and 24 months postoperatively. Relevant
      intra-articular lesions were documented. The patients were assigned to 1 of the
      following groups: (1) articular screw perforation, (2) subacromial plate
      impingement, or (3) post-traumatic/postoperative shoulder stiffness. Shoulder
      range of motion and function as measured with the age- and gender-adjusted
      Constant-Murley score, as well as the Simple Shoulder Test, were compared among
      the groups. RESULTS: Concomitant lesions of the articular cartilage, long head of
      the biceps tendon, tuberosities, and rotator cuff were found in 34 patients
      (75%). Two-thirds of patients (n = 31) had a partial or complete 270 degrees 
      capsular release. Of the patients, 84% (n = 38) underwent 3 and 12 months' follow
      up and 82% (n = 37) underwent 24 months' follow-up. The active range of abduction
      (P = .029), flexion (P = .048), and internal rotation (P = .0005) had improved
      significantly at 24 months' follow-up compared with the preoperative status. The
      mean adjusted Constant-Murley score of patients with post-traumatic shoulder
      stiffness (n = 15, 64.2% +/- 7.9%) and articular screw perforation (n = 19, 73.3%
      +/- 8.4%) was significantly lower (P = .0089 and P = .042, respectively) than
      that of patients with subacromial plate impingement (n = 12, 93.4% +/- 4.3%).
      CONCLUSIONS: High rates of relevant articular pathologies and the necessity of
      capsular release in a majority of patients with unsatisfactory results after
      locked plating of proximal humeral fractures make arthroscopy a valuable revision
      tool with promising results in cases of high plate positioning, screw
      perforation, and postoperative/post-traumatic shoulder stiffness. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 24939368
TI  - Congenital cystic eye associated with a low-grade cerebellar lesion that
      spontaneously regressed.
AB  - BACKGROUND: Congenital cystic eye is an exceedingly rare ocular malformative
      disease, originated from the failure in the invagination of the optic vesicle
      during the fetal period and it can be associated with other ocular and non-ocular
      abnormalities. Diagnosis is based on clinical, radiological and histological
      features. CASE PRESENTATION: We report a case of a congenital cystic eye
      associated with a cerebellar lesion accidentally detected at magnetic resonance
      imaging. Biopsy of the mass has not been performed due to parental rejection.
      Based on radiologic features and absence of clinical signs, a low-grade glioma
      diagnosis was hypothesized, but histological characterization was not obtained.
      Follow-up neuro-imaging 6 months after diagnosis showed that intracranial lesion
      spontaneously regressed without any treatment. CONCLUSION: Our report stresses
      the importance of early MRI in children with ocular malformations, in order to
      detect associated intracranial defects, also of non-malformative origin.
      Additionally, we debate the clinic-radiological features of the intracranial
      lesions that could allow a wait-and-see policy. We also recommend a strict
      clinical and neuro-imaging follow-up for these lesions. Finally, biological
      mechanisms at the base of spontaneous regression of the brain lesions are
      discussed.

PMID- 24939369
TI  - The multiple benefits of inserting interdisciplinary quality improvement teams
      led by medical students into a faculty practice primary care clinic.

PMID- 24939371
TI  - Glycans and galectins in prostate cancer biology, angiogenesis and metastasis.
AB  - Prostate cancer is the second most common cause of cancer and the sixth leading
      cause of cancer death among men worldwide. While localized prostate cancer can be
      cured, advanced and metastatic prostate cancer remains a significant therapeutic
      challenge. Malignant transformation is associated with important modifications of
      the cellular glycosylation profile, and it is postulated that these changes have
      a considerable relevance for tumor biology. Metastasis is a multiphasic process
      that encompasses angiogenesis, the spread of tumor cells and their growth at
      distant sites from the primary tumor location. Recognition of glycoconjugates by
      galectins, among other lectins, plays a fundamental role in the metastatic
      spread, tumor immune escape and the neovascularization process. Particularly in
      prostate cancer, both carbohydrates and galectins have been implicated in many
      cellular processes such as proliferation, apoptosis, migration and invasion.
      However, a limited number of studies assessed their potential implications in the
      induction of metastasis in prostate cancer patients or in animal models.
      Moreover, the role of galectin-glycan interactions in vivo still remains poorly
      understood; concerted effort should thus be made in order to shed some light on
      this question. This review summarizes current evidence on both the expression and
      role of glycans and galectins in prostate cancer, particularly turning our
      attention to the angiogenic and metastatic processes. 

PMID- 24939370
TI  - Galectin-8: a matricellular lectin with key roles in angiogenesis.
AB  - Galectin-8 (gal-8) is a "tandem-repeat"-type galectin, containing two
      carbohydrate recognition domains connected by a linker peptide. gal-8 is
      expressed both in the cytoplasm and nucleus in vascular endothelial cells (ECs)
      from normal and tumor-associated blood vessels, and in lymphatic endothelial
      cells. Herein, we describe a novel role for gal-8 in the regulation of vascular
      and lymphatic angiogenesis and provide evidence of its critical implications in
      tumor biology. Functional assays revealed central roles for gal-8 in the control
      of capillary-tube formation, EC migration and in vivo angiogenesis. So far, two
      endothelial ligands have been described for gal-8, namely podoplanin in lymphatic
      vessels and CD166 (ALCAM, activated leukocyte cell adhesion molecule) in vascular
      ECs. Other related gal-8 functions are also summarized here, including cell
      adhesion and migration, which collectively demonstrate the multi-functionality of
      this complex lectin. Thus, gal-8 is an important component of the angiogenesis
      network, and an essential molecule in the extracellular matrix by providing
      molecular anchoring to this surrounding matrix. The implications of gal-8 in
      tumor angiogenesis remain to be further explored, but it is exciting to speculate
      that modulating gal-8-glycan interactions could be used to block lymphatic
      vascular connections vital for metastasis. 

PMID- 24939372
TI  - Age-associated differences in triceps surae muscle composition and strength - an
      MRI-based cross-sectional comparison of contractile, adipose and connective
      tissue.
AB  - BACKGROUND: In human skeletal muscles, the aging process causes a decrease of
      contractile and a concomitant increase of intramuscular adipose (IMAT) and
      connective (IMCT) tissues. The accumulation of non-contractile tissues may
      contribute to the significant loss of intrinsic muscle strength typically
      observed at older age but their in vivo quantification is challenging. The
      purpose of this study was to establish MR imaging-based methods to quantify the
      relative amounts of IMCT, IMAT and contractile tissues in young and older human
      cohorts, and investigate their roles in determining age-associated changes in
      skeletal muscle strength. METHODS: Five young (31.6 +/- 7.0 yrs) and five older
      (83.4 +/- 3.2 yrs) Japanese women were subject to a detailed MR imaging protocol,
      including Fast Gradient Echo, Quantitative Fat/Water (IDEAL) and Ultra-short Echo
      Time (UTE) sequences, to determine contractile muscle tissue and IMAT within the
      entire Triceps Surae complex, and IMCT within both heads of the Gastrocnemius
      muscle. Specific force was calculated as the ratio of isometric plantarflexor
      force and the physiological cross-sectional area of the Triceps Surae complex.
      RESULTS: In the older cohort, total Triceps Surae volume was smaller by 17.5%,
      while the relative amounts of Triceps Surae IMAT and Gastrocnemius IMCT were
      larger by 55.1% and 48.9%, respectively. Differences of 38.6% and 42.1% in
      plantarflexor force and specific force were observed. After subtraction of IMAT
      and IMCT from total muscle volume, differences in intrinsic strength decreased to
      29.6%. CONCLUSIONS: Our data establishes that aging causes significant changes in
      skeletal muscle composition, with marked increases in non-contractile tissues.
      Such quantification of the remodeling process is likely to be of functional and
      clinical importance in elucidating the causes of the disproportionate age
      associated decrease of force compared to that of muscle volume.

PMID- 24939373
TI  - Vibrational characteristics of graphene sheets elucidated using an elastic
      network model.
AB  - Recent studies of graphene have demonstrated its great potential for highly
      sensitive resonators. In order to capture the intrinsic vibrational
      characteristics of graphene, we propose an atomistic modeling method called the
      elastic network model (ENM), in which a graphene sheet is modeled as a mass
      spring network of adjacent atoms connected by various linear springs with
      specific bond ratios. Normal mode analysis (NMA) reveals the various vibrational
      features of bi-layer graphene sheets (BLGSs) clamped at two edges. We also
      propose a coarse-graining (CG) method to extend our graphene study into the meso-
      and macroscales, at which experimental measurements and synthesis of graphene
      become practical. The simulation results show good agreement with experimental
      observations. Therefore, the proposed ENM approach will not only shed light on
      the theoretical study of graphene mechanics, but also play an important role in
      the design of highly-sensitive graphene-based resonators. 

PMID- 24939375
TI  - Don't forget diagnostic ultrasound.

PMID- 24939374
TI  - Triggers and treatment of anaphylaxis: an analysis of 4,000 cases from Germany,
      Austria and Switzerland.
AB  - BACKGROUND: Anaphylaxis is the most severe manifestation of a mast cell-dependent
      immediate reaction and may be fatal. According to data from the Berlin region,
      its incidence is 2-3 cases per 100 000 persons per year. METHOD: We evaluated
      data from the anaphylaxis registry of the German-speaking countries for 2006-2013
      and data from the protocols of the ADAC air rescue service for 2010-2011 to study
      the triggers, clinical manifestations, and treatment of anaphylaxis. RESULTS: The
      registry contained data on 4141 patients, and the ADAC air rescue protocols
      concerned 1123 patients. In the registry, the most common triggers for
      anaphylaxis were insect venom (n = 2074; 50.1%), foods (n = 1039; 25.1%), and
      drugs (n = 627; 15.1%). Within these groups, the most common triggers were wasp
      (n = 1460) and bee stings (n = 412), legumes (n = 241), animal proteins (n =
      225), and analgesic drugs (n = 277). Food anaphylaxis was most frequently induced
      by peanuts, cow milk, and hen's egg in children and by wheat and shellfish in
      adults. An analysis of the medical emergency cases revealed that epinephrine was
      given for grade 3 or 4 anaphylaxis to 14.5% and 43.9% (respectively) of the
      patients in the anaphylaxis registry and to 19% and 78% of the patients in the
      air rescue protocols. CONCLUSION: Wasp and bee venom, legumes, animal proteins,
      and analgesic drugs were the commonest triggers of anaphylaxis. Their relative
      frequency was age-dependent. Epinephrine was given too rarely, as it is
      recommended in the guidelines for all cases of grade 2 and above.

PMID- 24939376
TI  - In reply.

PMID- 24939378
TI  - Tailoring medical education to meet speciality needs.

PMID- 24939377
TI  - Fractures of the ankle joint: investigation and treatment options.
AB  - BACKGROUND: Ankle fractures are common, with an incidence of up to 174 cases per
      100 000 adults per year. Their correct classification and treatment are of
      decisive importance for clinical outcome. METHOD: Selective review of the
      literature. RESULTS: Ankle fractures are initially evaluated by physical
      examination and then by x-ray. They can be classified according to either the AO
      Foundation (Association for the Study of Internal Fixation) or the Weber
      classification. Dislocated fractures need emergency treatment with immediate
      reduction; this is crucial for the prevention of hypoperfusion and nerve damage.
      Weber A fractures can usually be treated conservatively, while Weber B and C
      fractures are usually treated with surgery. An evaluation of the stability of the
      syndesmosis is important for anatomical reconstruction of the joint. Wound
      hematoma and wound-edge necrosis are the most common complications, and the
      postoperative infection rate is 2%. Up to 10% of patients develop ankle arthrosis
      over the intermediate or long term. CONCLUSION: With properly chosen treatment, a
      good clinical outcome can be achieved. The long-term objective is to prevent post
      traumatic ankle arthrosis. The evidence level for optimal treatment strategies is
      low.

PMID- 24939379
TI  - Molecular simplification of lipid A structure: TLR4-modulating cationic and
      anionic amphiphiles.
AB  - A growing body of data suggests that therapies based on Toll-like receptors (TLR)
      targeting, in particular TLR4, holds promise in curing autoimmune and
      inflammatory pathologies still lacking specific treatment, included several rare
      diseases. While TLR4 activators (agonists) have already found successful clinical
      application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as
      antisepsis agents or as agents against inflammatory diseases (including
      arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a
      preclinical phase of development. This minireview focuses on recent achievements
      on the development of TLR4 modulators based on lipid A structure simplification,
      in particular on compounds having disaccharide or monosaccharide structures. As
      the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its
      biologically active part, the lipid A) depends on both the structure of endotoxin
      aggregates in solution and on single-molecule interaction with MD-2 and CD14
      receptors, the rational design of TLR4 modulators should in principle take into
      account both these factors. In the light of the most recent advances in the
      field, in this minireview we discuss the structure-activity relationship in
      simplified lipid A analogs, with cationic or anionic amphiphilic structures. 

PMID- 24939381
TI  - Nonconforming glenoid increases posterior glenohumeral translation after a total
      shoulder replacement.
AB  - BACKGROUND: The major complication in nonconforming total shoulder replacement
      (TSR) is glenoid loosening and is attributed to posteriorly directed humeral head
      translations. Whether the posterior translations observed clinically are induced
      by radial mismatch is unclear. The objective of our study was to explain the
      posterior glenohumeral translations observed clinically after TSR by determining
      the glenohumeral translation and contact force as a function of radial mismatch.
      We hypothesized that the posterior direction of glenohumeral translation during
      scaption would be related to the radial mismatch and that the joint contact force
      would increase as the radial mismatch increased. METHODS: A 6-degrees-of-freedom
      computational model of the glenohumeral joint was developed. We determined the
      muscle forces, joint contact force, and glenohumeral translation for radial
      mismatches from 1 mm to 20 mm with the shoulder positioned from 20 degrees  to 60
      degrees  of scaption. RESULTS: As the radial mismatch increased, the contact
      location of the humeral head moved posteriorly and inferiorly. The middle deltoid
      force decreased by 3%, while the supraspinatus and infraspinatus muscle forces
      increased by 9% and 11%, respectively. The joint contact force remained
      relatively constant. CONCLUSIONS: Increased posterior glenohumeral translations
      were observed with increased radial mismatch. Clinical observations of posterior
      translation may be attributed to the balancing forces of the middle deltoid,
      infraspinatus, and supraspinatus muscles. High radial mismatches may lead to
      eccentric posterior loading on the glenoid component, which could lead to implant
      loosening and failure.

PMID- 24939380
TI  - Electrothermal arthroscopic capsulorrhaphy: old technology, new evidence. A
      multicenter randomized clinical trial.
AB  - BACKGROUND: Radiofrequency technology for shoulder instability was rapidly
      adopted despite limited clinical evidence and a poor understanding of its
      indications. Reports of serious adverse events followed, leading to its
      abandonment. This paper presents findings from a multicenter randomized clinical
      trial evaluating the safety and efficacy of electrothermal arthroscopic
      capsulorrhaphy (ETAC) compared with open inferior capsular shift (ICS) and
      reviews the role of randomized trials in adopting new technology. METHODS:
      Patients (>14 years) diagnosed with multidirectional instability or
      multidirectional laxity with anteroinferior instability and failed nonoperative
      treatment were enrolled. Patients with bone lesions or labral, biceps anchor, or
      full-thickness rotator cuff tears were excluded intraoperatively. Outcomes
      included Western Ontario Shoulder Instability Index, function and recurrent
      instability at 2 years postoperatively, and surgical times. RESULTS: Fifty-four
      subjects (mean age, 23 years; 37 women) were randomized to ETAC (n = 28) or open
      ICS (n = 26). The groups were comparable at baseline, except for external
      rotation at the side. At 2 years postoperatively, there were no statistically or
      clinically significant differences between groups for the Western Ontario
      Shoulder Instability Index (P = .71), American Shoulder and Elbow Surgeons score
      (P = .43), Constant score (P = .43), and active range of motion. Recurrent
      instability was not statistically different (ETAC, 2; open, 4; P = .41). ETAC (23
      minutes) was significantly shorter than open ICS (59 minutes) (P < .01) surgery.
      Three subjects (1 ETAC, 2 open) had stiff shoulders. CONCLUSIONS: At 2 years
      postoperatively, quality of life and functional outcomes between groups were not
      clinically different. ETAC had fewer complications and episodes of recurrence
      compared with open surgery. This evidence reinforces the need to critically
      evaluate new technology before widespread clinical use.

PMID- 24939383
TI  - Reference interval determination for anabasine: a biomarker of active tobacco
      use.
AB  - Laboratory detection of nicotine exposure is important for establishing
      eligibility for organ transplant and elective surgery. Nicotine testing is also
      used to verify compliance with nicotine replacement therapies (NRT), smoking
      cessation programs and for life insurance purposes. Nicotine metabolites, such as
      cotinine and trans-3'-hydroxycotinine, are used as biomarkers of nicotine
      exposure. For some clinical applications, it is important to distinguish between
      active use of tobacco products versus NRT. Anabasine is a tobacco alkaloid that
      has been used as a biomarker of active tobacco use. However, the use of anabasine
      as an insecticide, and its presence in consumables other than nicotine products,
      suggests that anabasine may not be specific to tobacco use/exposure. Here, we
      determine the reference interval for anabasine in the urine of nonsmokers and
      compare it to the range of anabasine concentrations observed in the presence or
      absence of nicotine metabolites. 

PMID- 24939382
TI  - Thrombus aspiration in primary angioplasty for ST-segment elevation myocardial
      infarction.
AB  - Mechanical reperfusion with primary percutaneous coronary intervention in acute
      ST-segment-elevation myocardial infarction is superior to fibrinolysis in terms
      of short-term and long-term outcome, provided that it can be delivered on time
      and by an experienced team. Balloon angioplasty and stent implantation of an
      occluded epicardial vessel during ST-segment-elevation myocardial infarction can
      cause disruption of the frail thrombus containing lesions associated with
      suboptimal myocardial reperfusion and microcirculatory obstruction. Distal
      embolization of atherothrombotic material can be prevented by thrombus aspiration
      during primary angioplasty. Mechanical aspiration via end-hole large-lumen
      thrombectomy catheters has been shown to improve Thrombolysis in Myocardial
      Infarction (TIMI) flow and result in a more consistent early resolution of ST
      segment elevation in multiple registries. More recently, a more sophisticated
      quantification of the myocardial damage has been applied using myocardial
      scintigraphy and magnetic resonance, with no difference between patients treated
      with thrombectomy and patients treated with conventional therapy. The
      expectations in terms of lasting mortality benefit raised by the first Dutch
      single-center randomized trial of thrombectomy versus predilation with plain old
      balloon angioplasty (Thrombus Aspiration During Percutaneous Coronary
      Intervention in Acute Myocardial Infarction, TAPAS) were not confirmed by a much
      larger Swedish trial (Thrombus Aspiration ST-Segment Elevation Myocardial
      Infarction, TASTE) showing no outcome changes. Although we are waiting for new
      trials to clarify these controversial results, thrombectomy is still used in
      selected patients with high thrombus load or with persistent occlusion of the
      infarct-related artery after wire passage. Here we review the various systems
      available and discuss their relative merits and the reported results. 

PMID- 24939384
TI  - The diversity of bacteria isolated from antarctic freshwater reservoirs
      possessing the ability to produce polyhydroxyalkanoates.
AB  - The diversity of polyhydroxyalkanoates-producing bacteria in freshwater
      reservoirs in the Ecology Glacier foreland, Antarctica, was examined by a
      cultivation-dependent method. Isolated strains were analyzed phylogenetically by
      16S rRNA gene sequencing, and classified as members of Alpha-, Beta-, or
      Gammaproteobacteria classes. Polymerase chain reaction was used to detect PHA
      synthase genes. Potential polyhydroxyalkanoates (PHAs) producers belonging mainly
      to Pseudomonas sp., and Janthinobacterium sp. were isolated from all five
      sampling sites, suggesting that PHA synthesis is a common bacterial feature at
      pioneer sites. All Pseudomonas strains had the genetic potential to synthesize
      medium-chain-length PHAs, whereas some isolated Janthinobacterium strains might
      produce short-chain-length PHAs or medium-chain-length PHAs. It is the first
      report revealing that Janthinobacterium species could have the potential to
      produce medium-chain-length PHAs. 

PMID- 24939385
TI  - The DosR dormancy regulator of Mycobacterium tuberculosis stimulates the Na(+)/K
      (+) and Ca (2+) ATPase activities in plasma membrane vesicles of mycobacteria.
AB  - The latency global regulator DosR regulon of Mycobacterium tuberculosis, which is
      stimulated by hypoxia, comprises approximately fifty genes including ctpF
      (Rv1997), which encodes a putative alkali/alkaline earth ion transporter of the
      plasma membrane. In this work, the influence of hypoxia and M. tuberculosis DosR
      on the ATPase activity of mycobacterial plasma membrane was assessed. We
      performed bioinformatic analyses which indicated that the pma1 gene product is
      the M. smegmatis ortholog of the M. tuberculosis cation transporter CtpF. In
      addition, a possible Na(+), K(+) and/or Ca(2+) pumping mediated by Pma1 was also
      predicted. Enzymatic analyses indicated that the basal ATPase activity of plasma
      membrane vesicles from M. smegmatis cells cultured under hypoxia and over
      expressing DosR, decreased 30 and 40 % respectively in comparison to oxygenated
      cells. In contrast, the specific Na(+)/K(+) and Ca(2+) ATPase activities of the
      plasma membrane increased 2.8- and 3.5-fold, respectively, under hypoxia, similar
      to that observed for cells over-expressing the DosR regulator. In agreement, RT
      qPCR experiments demonstrated that the transcription level of the pma1 gene
      increased under hypoxia at levels similar to that of M. smegmatis cells over
      expressing the M. tuberculosis DosR regulator. The entire findings suggest that
      hypoxia stimulates Na(+)/K(+) and Ca(2+) ATPase activities in the mycobacterial
      plasma membrane, and this is possibly mediated by the dormancy regulator DosR. 

PMID- 24939386
TI  - Heat stress induces apoptotic-like cell death in two Pleurotus species.
AB  - High temperature is an important environmental factor that affects the growth and
      development of most edible fungi, however, the mechanism(s) for resistance to
      high temperature remains elusive. Nitric oxide is known to be able to effectively
      alleviate oxidative damage and plays an important role in the regulation of
      trehalose accumulation during heat stress in mycelia of Pleurotus eryngii var.
      tuoliensis. In this paper, we investigated whether heat stress can activate
      apoptosis-like cell death in mycelia of Pleurotus. Two Pleurotus species were
      used to detect morphological features characteristic of apoptosis including
      nuclear condensation, reactive oxygen species accumulation, and DNA fragmentation
      when exposed to heat stress (42  degrees C). The results showed that these
      classical apoptosis markers were apparent in Pleurotus strains after heat
      treatment. The heat-induced apoptosis-like cell death in Pleurotus was further
      probed using oligomycin and N-acetylcysteine, both of which were shown to block
      processes leading to apoptosis. This is the first report that apoptosis-like cell
      death occurs in Pleurotus species as a result of abiotic stress, and that this
      process can be inhibited with chemicals that block mitochondrial-induced
      apoptotic pathways and/or with ROS-scavenging compounds. 

PMID- 24939387
TI  - Female-specific gene expression in dioecious liverwort Pellia endiviifolia is
      developmentally regulated and connected to archegonia production.
AB  - BACKGROUND: In flowering plants a number of genes have been identified which
      control the transition from a vegetative to generative phase of life cycle. In
      bryophytes representing basal lineage of land plants, there is little data
      regarding the mechanisms that control this transition. Two species from
      bryophytes - moss Physcomitrella patens and liverwort Marchantia polymorpha are
      under advanced molecular and genetic research. The goal of our study was to
      identify genes connected to female gametophyte development and archegonia
      production in the dioecious liverwort Pellia endiviifolia species B, which is
      representative of the most basal lineage of the simple thalloid liverworts.
      RESULTS: The utility of the RDA-cDNA technique allowed us to identify three genes
      specifically expressed in the female individuals of P.endiviifolia: PenB_CYSP
      coding for cysteine protease, PenB_MT2 and PenB_MT3 coding for Mysterious
      Transcripts1 and 2 containing ORFs of 143 and 177 amino acid residues in length,
      respectively. The exon-intron structure of all three genes has been characterized
      and pre-mRNA processing was investigated. Interestingly, five mRNA isoforms are
      produced from the PenB_MT2 gene, which result from alternative splicing within
      the second and third exon. All observed splicing events take place within the
      5'UTR and do not interfere with the coding sequence. All three genes are
      exclusively expressed in the female individuals, regardless of whether they were
      cultured in vitro or were collected from a natural habitat. Moreover we observed
      ten-fold increased transcripts level for all three genes in the archegonial
      tissue in comparison to the vegetative parts of the same female thalli grown in
      natural habitat suggesting their connection to archegonia development.
      CONCLUSIONS: We have identified three genes which are specifically expressed in
      P.endiviifolia sp B female gametophytes. Moreover, their expression is connected
      to the female sex-organ differentiation and is developmentally regulated. The
      contribution of the identified genes may be crucial for successful liverwort
      sexual reproduction.

PMID- 24939388
TI  - Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune
      response in mice.
AB  - BACKGROUND: Innate lymphoid cells (ILCs) play important roles in innate immunity
      and tissue remodeling via production of various cytokines and growth factors.
      Group 2 ILCs (ILC2s) were recently shown to mediate the immune pathology of
      asthma even without adaptive immunity. However, little is known about possible
      interactions between ILC2s and other immune cells. We sought to investigate the
      capacity of ILC2s to regulate effector functions of T cells. METHODS: We isolated
      ILC2s from the lungs of naive mice. We cultured CD4(+) T cells with ILC2s in
      vitro and examined the functions of these cell types. The mechanisms were
      investigated using blocking antibodies and cells isolated from cytokine-deficient
      mice. For the in vivo study, we adoptively transferred ILC2s and CD4(+) T cells
      into Il7ra(-/-) mice and subsequently exposed the mice to ovalbumin and a
      cysteine protease. RESULTS: Lung ILC2s enhanced CD4(+) T-cell proliferation and
      promoted production of type 2 cytokines in vitro. The interaction between ILC2s
      and CD4(+) T cells involved costimulatory molecule OX40L and cytokine IL-4, which
      was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4(+) T-cell
      populations, but not each population alone, into Il7ra(-/-) mice resulted in
      induction of a robust antigen-specific type 2 cytokine response and airway
      inflammation. CONCLUSION: Lung ILC2s function to promote adaptive immunity in
      addition to their established roles in innate immunity. This novel function of
      ILC2s needs to be taken into account when considering the pathophysiology of
      asthma and other allergic airway diseases.

PMID- 24939390
TI  - A Process Evaluation of an HIV/STI Intervention for Rural African American Youth.
AB  - We evaluated the fidelity and implementation of an HIV/AIDS and sexually
      transmitted infections intervention for rural African American youth. Using a
      community-based evaluation approach, community partners and researchers monitored
      four core process-evaluation components: reach, fidelity, dose delivered, and
      dose received. Researchers collected evaluation data through session
      observations, facilitator debriefing interviews, a youth focus group, and a
      satisfaction survey. For reach, more than half of the participants attended the
      13 sessions. Participation varied between 62% and 100%. For fidelity, not all
      sessions were implemented as intended; multiple modifications occurred across
      sessions. For dose delivered, some lessons were missing materials and content was
      omitted; facilitators omitted content when there was insufficient time to
      complete a lesson. For dose received, engagement varied across lessons but youth
      reported high levels of satisfaction with the intervention. This formative
      process evaluation enabled us to identify and address multiple challenges to
      implementation.

PMID- 24939389
TI  - Prevalence of severe childhood asthma according to the WHO.
AB  - BACKGROUND: The World Health Organization (WHO) recently proposed a new
      definition of severe asthma to facilitate standardized characterization of
      patients, and enable more accurate estimations of the prevalence of severe
      asthma. The aim of this study was to estimate the prevalence of severe asthma
      according to the WHO definition in children aged 12 years, in Stockholm, Sweden.
      METHODS: The birth cohort BAMSE enrolled 4089 children during 1994-96. Parental
      questionnaires provided information on asthma-related symptoms, diagnosis and
      medication from 3015 enrolled children at the age of 12 years. Severe asthma was
      defined as the presence of asthma, as well as continuous treatment with inhaled
      corticosteroids and long-acting beta-2 agonists, based on information from the
      Swedish prescribed drug register demonstrating prescriptions of at least 800 MUg
      budesonide daily (or equivalent). RESULTS: The prevalence of asthma was 11% among
      12-year-olds (n = 329). Based on information from the Swedish prescribed drug
      register, seven children with asthma fulfilled the definition of severe asthma.
      The estimated prevalence corresponds to 0.23% (95% CI, 0.06-0.4) of the
      population, or 2.1% (95% CI, 0.5-3.7) of children with asthma. Based on assessed
      markers of asthma control, 3/7 with severe asthma were considered to have
      controlled asthma and 4/7 had partly or uncontrolled asthma. CONCLUSION: Severe
      asthma appears rare both among 12-year-old schoolchildren with asthma and in the
      general population. Combining self-reported information from a population-based
      birth cohort with data from a drug register seems trustworthy in estimating
      severe asthma as defined by the WHO.

PMID- 24939391
TI  - Understanding the Needs of Food-Allergic Adults.
AB  - Food allergies are a growing issue, yet society's understanding of how
      individuals' lives are affected is limited. We conducted four focus groups with
      food-allergic adults in New Zealand to gain an in-depth understanding of the
      issues that impacted their quality of life. Key themes identified included
      allergen-free eating issues, health care system issues, costs of having a food
      allergy, effects on well-being, external influences (e.g., others' lack of
      awareness), and internal influences (personal growth and adaptation). The unmet
      needs of food-allergic adults led to risk taking, increased stress, and social
      isolation. A lack of awareness in others (including medical professionals, food
      service providers, and the general public) had a negative impact, suggesting that
      an intervention targeting awareness would be beneficial. Adaptation, particularly
      in terms of assertiveness and organizational skills, was important for coping, so
      we suggest training in these skills be made available for food-allergic patients.

PMID- 24939393
TI  - Functional links between stability and reactivity of strontium ruthenate single
      crystals during oxygen evolution.
AB  - In developing cost-effective complex oxide materials for the oxygen evolution
      reaction, it is critical to establish the missing links between structure and
      function at the atomic level. The fundamental and practical implications of the
      relationship on any oxide surface are prerequisite to the design of new stable
      and active materials. Here we report an intimate relationship between the
      stability and reactivity of oxide catalysts in exploring the reaction on
      strontium ruthenate single-crystal thin films in alkaline environments. We
      determine that for strontium ruthenate films with the same conductance, the
      degree of stability, decreasing in the order (001)>(110)>(111), is inversely
      proportional to the activity. Both stability and reactivity are governed by the
      potential-induced transformation of stable Ru(4+) to unstable Ru(n>4+). This
      ordered(Ru(4+))-to-disordered(Ru(n>4+)) transition and the development of active
      sites for the reaction are determined by a synergy between electronic and
      morphological effects. 

PMID- 24939392
TI  - Evolution of eukaryotic single-stranded DNA viruses of the Bidnaviridae family
      from genes of four other groups of widely different viruses.
AB  - Single-stranded (ss)DNA viruses are extremely widespread, infect diverse hosts
      from all three domains of life and include important pathogens. Most ssDNA
      viruses possess small genomes that replicate by the rolling-circle-like mechanism
      initiated by a distinct virus-encoded endonuclease. However, viruses of the
      family Bidnaviridae, instead of the endonuclease, encode a protein-primed type B
      DNA polymerase (PolB) and hence break this pattern. We investigated the
      provenance of all bidnavirus genes and uncover an unexpected turbulent
      evolutionary history of these unique viruses. Our analysis strongly suggests that
      bidnaviruses evolved from a parvovirus ancestor from which they inherit a jelly
      roll capsid protein and a superfamily 3 helicase. The radiation of bidnaviruses
      from parvoviruses was probably triggered by integration of the ancestral
      parvovirus genome into a large virus-derived DNA transposon of the Polinton
      (polintovirus) family resulting in the acquisition of the polintovirus PolB gene
      along with terminal inverted repeats. Bidnavirus genes for a receptor-binding
      protein and a potential novel antiviral defense modulator are derived from dsRNA
      viruses (Reoviridae) and dsDNA viruses (Baculoviridae), respectively. The unusual
      evolutionary history of bidnaviruses emphasizes the key role of horizontal gene
      transfer, sometimes between viruses with completely different genomes but
      occupying the same niche, in the emergence of new viral types. 

PMID- 24939395
TI  - MICROPERC: calibration of the needle MicroPNL, Micro. What about its length?

PMID- 24939394
TI  - Serovar distribution, antimicrobial resistance profiles, and PFGE typing of
      Salmonella enterica strains isolated from 2007-2012 in Guangdong, China.
AB  - BACKGROUND: Salmonella enterica includes the major serovars associated with human
      salmonellosis. In this study, 1764 clinical Salmonella enterica isolates from
      diarrhea outpatients were collected from fifteen cities in Guangdong province,
      China, between 2007 and 2012. These isolates represent all of the Salmonella
      isolates collected from the province during that period. METHODS: The isolates
      were characterized by serovar determination, antimicrobial susceptibility tests
      and PFGE fingerprint typing. RESULTS: The serovar distribution results
      demonstrated that Salmonella Typhimurium (n=523, 29.65%) and Salmonella 4,5,12:i:
      (n=244, 13.83%) are the most common serovars causing infant salmonellosis,
      whereas Salmonella Enteritidis (n=257, 14.57%) mainly causes human salmonellosis
      in adults. The serovar shift from Salmonella Enteritidis to Salmonella
      Typhimurium occurred in 2008. Antimicrobial susceptibility data showed a high
      burden of multidrug resistance (MDR) (n=1128, 56.58%), and a 20%-30% increase in
      the number of isolates resistant to ciprofloxacin (n=142, 8.05%) and third
      generation cephalosporins (n=88, 4.99%) from 2007-2012. Only 9.97% of isolates
      (n=176) were fully susceptible to all agents tested. A high burden of MDR was
      observed in Salmonella Typhimurium and Salmonella 4,5,12:i:- for all age groups,
      and a reduced susceptibility to third-generation cephalosporins and quinolones
      occurred particularly in infants (<= 6 years). The dominant PFGE patterns were
      JPXX01.GD0004, JEGX01.GD0006-7 and JNGX01.GD0006-7. ACSSuT was the predominant
      MDR profile in the Salmonella Typhimurium & 4,5,12:i:- complexes, while ASSuT-Nal
      and ASSu-Nal were the major MDR profiles in Salmonella Enteritidis. The
      predominant PFGE patterns of the Salmonella Typhimurium & 4,5,12:i:- complexes
      and Salmonella Stanley were most prevalent in infants (<= 6 years). However, no
      obvious relationship was observed between these PFGE profiles and geographic
      location. CONCLUSIONS: These data reveal the serovar distribution of isolates
      recovered from diarrhea patients, the characteristics of resistant strains and
      fingerprint typing in Guangdong from 2007 to 2012. These results highlight a
      serovar shift and a worrying percentage of MDR strains with increasing resistance
      to quinolones and third-generation cephalosporins. Thus, continued surveillance
      of Salmonella and their MDR profiles using combined molecular tools and efforts
      to control the rapid increase in antimicrobial resistance among Salmonella in
      Guangdong are needed.

PMID- 24939396
TI  - Sexual violence and mode of delivery: a population-based cohort study.
AB  - OBJECTIVE: This study aimed to explore the association between sexual violence
      and mode of delivery. DESIGN: National cohort study. SETTING: Women presenting
      for routine ultrasound examinations were recruited to the Norwegian Mother and
      Child Cohort Study between 1999 and 2008. POPULATION: A total of 74,059 pregnant
      women. METHODS: Sexual violence was self-reported during pregnancy using postal
      questionnaires. Mode of delivery, other maternal birth outcomes and covariates
      were retrieved from the Medical Birth Registry of Norway. Risk estimations were
      performed using multivariable logistic regression analysis. MAIN OUTCOME
      MEASURES: Mode of delivery and selected maternal birth outcomes. RESULTS: Of
      74,059 women, 18.4% reported a history of sexual violence. A total of 10% had an
      operative vaginal birth, 4.9% had elective caesarean section and 8.6% had an
      emergency caesarean section. Severe sexual violence (rape) was associated with
      elective caesarean section, adjusted odds ratio (AOR) 1.56 (95% CI 1.18-2.05) for
      nulliparous women and 1.37 (1.06-1.76) for multiparous women. Those exposed to
      moderate sexual violence had a higher risk of emergency caesarean section, AOR
      1.31 (1.07-1.60) and 1.41 (1.08-1.84) for nulliparous and multiparous women,
      respectively. No association was found between sexual violence and operative
      vaginal birth, except for a lower risk among multiparous women reporting mild
      sexual violence, AOR 0.73 (0.60-0.89). Analysis of other maternal outcomes showed
      a reduced risk of episiotomy for women reporting rape and a higher frequency of
      induced labour. CONCLUSIONS: Women with a history of rape had higher odds of
      elective caesarean section and induction and significantly fewer episiotomies.

PMID- 24939397
TI  - Rhodium-catalyzed asymmetric hydrogenation of unprotected NH imines assisted by a
      thiourea.
AB  - Asymmetric hydrogenation of unprotected NH imines catalyzed by
      rhodium/bis(phosphine)-thiourea provided chiral amines with up to 97% yield and
      95% ee. (1)H NMR studies, coupled with control experiments, implied that
      catalytic chloride-bound intermediates were involved in the mechanism through a
      dual hydrogen-bonding interaction. Deuteration experiments proved that the
      hydrogenation proceeded through a pathway consistent with an imine.

PMID- 24939399
TI  - [The medication adherence in the elderly: a collective goal].

PMID- 24939398
TI  - Maximum-likelihood estimation of channel-dependent trial-to-trial variability of
      auditory evoked brain responses in MEG.
AB  - BACKGROUND: We propose a mathematical model for multichannel assessment of the
      trial-to-trial variability of auditory evoked brain responses in
      magnetoencephalography (MEG). METHODS: Following the work of de Munck et al., our
      approach is based on the maximum likelihood estimation and involves an
      approximation of the spatio-temporal covariance of the contaminating background
      noise by means of the Kronecker product of its spatial and temporal covariance
      matrices. Extending the work of de Munck et al., where the trial-to-trial
      variability of the responses was considered identical to all channels, we
      evaluate it for each individual channel. RESULTS: Simulations with two equivalent
      current dipoles (ECDs) with different trial-to-trial variability, one seeded in
      each of the auditory cortices, were used to study the applicability of the
      proposed methodology on the sensor level and revealed spatial selectivity of the
      trial-to-trial estimates. In addition, we simulated a scenario with neighboring
      ECDs, to show limitations of the method. We also present an illustrative example
      of the application of this methodology to real MEG data taken from an auditory
      experimental paradigm, where we found hemispheric lateralization of the
      habituation effect to multiple stimulus presentation. CONCLUSIONS: The proposed
      algorithm is capable of reconstructing lateralization effects of the trial-to
      trial variability of evoked responses, i.e. when an ECD of only one hemisphere
      habituates, whereas the activity of the other hemisphere is not subject to
      habituation. Hence, it may be a useful tool in paradigms that assume
      lateralization effects, like, e.g., those involving language processing.

PMID- 24939400
TI  - [The French Society of Geriatrics and Gerontology position paper on the concept
      of integration. Part two].
AB  - The concept of integrated services delivery, although dating from the 1990s, has
      only recently appeared in French public health policy. To clarify the concept and
      its adaptation to the reality of the French systems of healthcare and social
      services, the French Society of Geriatrics and Gerontology established an
      interdisciplinary working group. This article reports that group's findings
      according to three axes: the definition of integration, the objectives of this
      organizational approach and the means needed to achieve them. Analysis of the
      literature indicated that integration is a process that aims to overcome the
      fragmentation of services for vulnerable people. This process requires a
      multilevel approach, particularly concerning how to modify public policies and
      financing systems. Notably, all relevant levels need to develop shared processes,
      tools, resources, finance, interventions and returns on the latter. Indeed, this
      sharing is the ultimate proof of evolution towards integration. In the second
      part of the position paper, its authors have developed arguments that could lead
      professionals and non-professional caregivers to adopt integrated care as an
      answer to their aspirations. Policy-maker perspectives and politicians are also
      analyzed. Bearing in mind that integrated care necessarily will always involve a
      human component which may find expression during individual case-management;
      relations between integration and case managements are clarified. Finally,
      lessons learned from national and international experiments are examined. Results
      suggest that integrated care must to be accompanied by a local pilot. Results of
      recent experiments have shown that it is possible to initiate a dynamic towards
      integrated care in France and hence join the international movement towards
      adapting our healthcare systems to new challenges. 

PMID- 24939401
TI  - [Impact of double stigmatization in oncogeriatry: reviewing existing data].
AB  - Cancer is a major health problem for which age is a proved risk factor.
      Paradoxically, elderly suffering from cancer are often excluded from clinical
      trials and undertreated compared to younger patients. Also, their psychosocial
      needs remain unknown. An explanatory factor for these observations is the age
      stigma (that is to say our stereotypes about age and so, ageism), age being
      currently cited as the main reason for discrimination. Besides these age-related
      stigmas, cancerous patients face pathology-related stigmas because nowadays
      cancer (especially some types of cancer such as lung cancer) still conveys a lot
      of negative representations. These observations bring us to the notion of double
      stigmatization in oncogeriatry. Moreover, the aim of this review is to present
      ageism phenomenon on the basis of several studies that had proved negative
      influence of ageism on elderly's mental and physical health and on the attitude
      of elderly's interlocutors. Afterwards, we will broach the way by which ageism
      and stigmatization linked to cancer is observed in the specific context of
      oncogeriatry, which will allow us to identify current shortcomings. 

PMID- 24939402
TI  - [Evaluation tools of drug adherence for elderly subjects: towards a new pattern
      of scale].
AB  - INTRODUCTION: Medication non-adherence can be defined as a non-compliance with
      prescribed drugs. The characteristics of elderly people constitute major risk
      factors for non-adherence to medication. The aim of this study was to study the
      relevance of medication adherence scales that are identified in a previous work.
      METHODS: The current study was based on a previous work in which several
      adherence scales were identified. We reviewed articles that validated these
      scales to assess their performances and to measure their adaptation for elderly
      people. RESULTS: Eight scales were studied, of whom five were validated in high
      blood pressure therapy. Intrinsic performance as well as construction and
      validation of scales were weak. Furthermore, none of these validation studies
      were conducted in elderly population aged 75 years and over. Four aspects
      appeared to be necessary for scale development: knowledge of the disease and its
      treatment, perception of the efficacy and tolerance of the treatment, getting the
      therapy, and drug administration. The use of an evaluation scale in elderly
      population should consider the living location, the ability of the subject to
      respond, and the presence of informal or formal caregivers. CONCLUSIONS: Existing
      scales seem to be weak and elderly characteristics are not considered. Validated
      adherence medication scales adapted for elderly people are thus needed.

PMID- 24939403
TI  - [Qualitative approach of medical support of spouse caregivers of Alzheimer
      patients].
AB  - BACKGROUND: The caregivers of patients with Alzheimer's disease (AD) play a key
      role in their management. Half of them are spouses. This involvement may alter
      their own health, leading to exhaustion and depression. Since 2010, general
      practitioners (GPs) have been invited in France to offer an annual specific
      medical support to spouse caregivers. The aims of this study were to understand
      their experience of this situation by spouse caregivers, and how the spouse
      caregiver perceives the role of the GP in this context. METHODS: A qualitative
      approach was conducted using semi-structured interviews of 14 spouse caregivers
      recruited from adult day care in Angers, France. RESULTS: The analysis of
      interviews showed that AD was an existential crisis for the dyad AD
      patient/spouse caregiver. The emotional connection and the sense of commitment
      strongly involved the spouse caregivers into cares for the loved ones. Even if
      the frequency of medical consultations remained unchanged, caregivers were more
      prone to delay non-urgent cares for themselves. Moreover their intention to
      handle things on their own and the interaction with health professionals of the
      care recipients interfered with the involvement of the caregivers' GPs.
      CONCLUSIONS: Caregivers' adaptation to their spouses' AD resulted in both
      negative and positive behaviors. Instead of a mandatory annual consultation
      focused on caregivers' health, the improvement of communication between all
      support services, including caregivers' GPs, may help to enhance the medical
      support of spouse caregivers of AD patients.

PMID- 24939405
TI  - [Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy].
AB  - CADASIL is an inherited small vessel disease of the brain caused by mutations of
      the NOTCH3 gene encoding a receptor of smooth muscle cells and pericytes within
      the wall of arterioles and capillaries. The mutated gene is responsible for
      accumulation of NOTCH3 protein and aggregation of various proteins in the
      vascular wall. The disease occurs during mid-adulthood and is responsible for
      attacks of migraine with aura, ischemic stroke, mood disorders and cognitive
      impairment ranging from mild alterations of attentional performances and
      executive functions to severe dementia. The disease develops in adults with aging
      and is responsible at the latest stage of gait and balance troubles associated
      with cognitive impairment that may lead to severe disability and dependence. MRI
      shows widespread white matter lesions that may involve the anterior part of
      temporal lobes often associated with small cerebral infarcts and with
      microbleeds. The clinical severity is related to accumulation of small infarcts
      and the development of cerebral atrophy over time. The diagnosis of the disease
      is confirmed by genetic testing or skin biopsy. 

PMID- 24939404
TI  - [Comparative study of two on aged care-based occupational (professional) training
      in medical home for aged and dependent patients with neuropsychiatric behaviors].
AB  - BACKGROUND: Neuropsychiatric behaviours of the elderly is the main issue for
      caregivers' distress, burn out and high turn-over. This situation will steadily
      worsen with longer lifetime. AIM OF THE STUDY: Specialised training of medical
      staff may decrease their distress: we compare both training programs
      Humanitude(r) et Formadep(r) outcomes. METHODS: A comparative open multicentric
      non randomised study included 459 elderlies of 9 EHPAD of Korian Company into 3
      training groups: Humanitude(r), Formadep(r) and a group control, with 29 weeks
      follow-up. We studied the scoring NPI-ES (FG and R), BMS-10, ECPA and GIR,
      medications, caregivers' burn out/absences/turn-over levels. Statistical
      significance were done by Wilcoxon signed-rank test, Ancova and linear
      regression. RESULTS: 320 caregivers and 3 groups of nearly 150 elderlies each,
      with around 50% dementia. In Formadep(r) group : lower scoring for a short time
      of total NPI-R (p<0.05), sustained lower scoring of NPI-FG "
      agitation/agressivity" (p=0.035) but transitional for its NPI-R (p<0.05),
      sustained higher scoring of NPI-FG "apathy/indifference" (p=0.002) but
      transitional for its NPI-R (p=0 .003), sustained lower scoring of NPI-R
      (p=0.0039) for Motor Aberrant Behaviours (MAB). In Humanitude(r) group:
      transitional higher scoring of NPI-R (p=0.025) for MAB et transitional lower
      scoring NPI-R (p=0.0032) for depression (Alzheimer Disease sub-groupe). No change
      for other parameters. CONCLUSION: Despite high variability of the
      neuropsychiatric behaviours in elderly, Formadep(r) training has shown a positive
      impact on the global distress and on three main challenging behaviours, compared
      to Humanitude(r): this may be depend on their own philosophy. But caregivers'
      burden in dementia is not a one-factor problem.

PMID- 24939406
TI  - [Contribution of psychoanalysis to geriatric care for institutionalized
      patients].
AB  - The contribution of psychoanalysis to geriatric care in nursing home is discussed
      in three directions: its conception of care, specially on its negative sides; its
      implication in geriatric units, in their conception and in the analysis of their
      management of care; the holding of care-givers and nurses by making clear what we
      call transference and conter-transference and their reflection on their function.

PMID- 24939407
TI  - [Language deficits in major forms of dementia and primary progressive aphasias:
      an update according to new diagnostic criteria].
AB  - In this review, we report current data on spoken and written language disorders
      in the most frequent dementia syndromes, namely Alzheimer' disease, vascular
      cognitive impairment and dementia with Lewy bodies. Language deficits are also
      the core features of three variants of primary progressive aphasia, namely the
      nonfluent/agrammatic, semantic and logopenic variants. This review reveals that,
      like other cognitive functions, language is highly vulnerable to
      neurodegenerative diseases. For some, language deficits result from impairment in
      linguistic processes per se, while for others, they are the direct consequence of
      impairments affecting working memory and executive functions. Language deficits
      in Alzheimer's disease and in nonfluent/agrammatic and semantic variants of
      primary progressive aphasia are well documented. By contrast, those about
      vascular cognitive impairment and dementia with Lewy bodies remain scarce and
      limited to large cognitive domains. The identification of logopenic variant of
      primary progressive aphasia is very recent, and more research is needed to
      complete the clinical description and identification of the functional origin of
      the disorders. Finally, knowledge on the impairment of written language in
      neurodegenerative diseases is less well documented than those on spoken language
      deficits. Other studies are therefore needed to improve the description of
      linguistic profiles and to provide additional elements to help in the
      differential diagnosis. 

PMID- 24939408
TI  - [Personality disorders and aging].
AB  - Personality disorder can be defined as an enduring pattern of inner experience
      and behavior that markedly deviates from the expectations of the individual's
      culture. With aging, personality disorders may improve or worsen. Their
      prevalence in the elderly is slightly lower than the prevalence in young adult.
      Furthermore, their comorbidity and co-occurrence are the rule with an increased
      risk of late decompensation. Categorical approach used in the current
      international classifications (ICD-10 and DSM-5) is not adapted to the
      specificities of the elderly with consequent overrepresentation of "unspecified
      personality disorder". However, a pathological personality tends to complicate
      all interventions for somatic or psychological care in the elderly. Thus, this
      review describes changes in personality disorders related to aging in order to
      help the clinician to better identify these disorders. Indeed, recognizing a
      pathological personality in the elderly improves its management both in the field
      of mental health and in somatic disorders in which the role of personality must
      be evaluated. Personality and its disorders should therefore be taken into
      account in all geriatric practices, in particular in the context of cognitive
      disorders. 

PMID- 24939409
TI  - [A comparison of the performances between healthy older adults and persons with
      Alzheimer's disease on the Rey auditory verbal learning test and the Test de
      rappel libre/rappel indice 16 items].
AB  - The aim of this research was to compare the performances of healthy elderly
      (n=40) and individuals with Alzheimer's disease (AD, n=40) on the RL/RI 16, a
      French adaptation of the Free and cued selective reminding test (FCSRT) and on
      the Rey auditory verbal learning test (RAVLT). These two verbal episodic memory
      tests are frequently used in clinical practice in French-speaking populations.
      Results showed that the RAVLT demonstrated a slightly better sensitivity and
      sensibility than the RL/RI 16. The RAVLT allowed to classify participants of the
      two groups without any overlap. Moreover, no floor effect was observed in the
      RAVLT in AD and ceiling effects were less pronounced in normal controls that in
      the RL/RI 16. Results observed in the RL/RI 16 showed important ceiling effects
      and a decline in performance on free recall throughout trials in AD patients.
      Nonetheless, the latter tool was less sensitive to recency effects than the RAVLT
      and may thus provide a more realistic view of the long-term memory performance of
      these patients. The semantic cues provided in the RL/RI 16 appeared to increase
      intrusions in AD whereas the interference list in the RAVLT was the first source
      of false recognitions in both healthy elderly and AD. In conclusion, this paper
      demonstrates both the advantages and disadvantages of these two tools in the
      evaluation of episodic memory in elderly with and without cognitive deficits. 

PMID- 24939410
TI  - [A motivational approach of cognitive efficiency in nursing home residents].
AB  - Despite a widespread concern with self-determined motivation (behavior is engaged
      in "out of pleasure" or "out of choice and valued as being important") and
      psychological adjustment in later life (well-being, satisfaction in life, meaning
      of life, or self-esteem), very little is known about the existence and nature of
      the links between self-determined motivation and cognitive efficiency. The aim of
      the present study was to investigate theses links in nursing home residents in
      the framework of the Self-determination theory (SDT) (Deci & Ryan, 2002), in
      which motivational profile of a person is determined by the combination of
      different kinds of motivation. We hypothesized that self-determined motivation
      would lead to higher cognitive efficiency. Participants. 39 (32 women and 7 men)
      elderly nursing home residents (m= 83.6 +/- 9.3 year old) without any
      neurological or psychiatric disorders (DSM IV) or depression or anxiety (Hamilton
      depression rating scales) were included in the study. Methods. Cognitive
      efficiency was evaluated by two brief neuropsychological tests, the Mini mental
      state examination (MMSE) and the Frontal assessment battery (FAB). The
      motivational profile was assessed by the Elderly motivation scale (Vallerand &
      0'Connor, 1991) which includes four subscales assessing self- and non-self
      determined motivation to engage oneself in different domains of daily life
      activity. Results. The neuropsychological scores were positively and
      significantly correlated to self-determined extrinsic motivation (behavior is
      engaged in "out of choice" and valued as being important), and the global self
      determination index (self-determined motivational profile) was the best predictor
      of the cognitive efficiency. Conclusion. The results support the SDT interest for
      a qualitative assessment of the motivation of the elderly people and suggest that
      a motivational approach of cognitive efficiency could help to interpret cognitive
      performances exhibited during neuropsychological assessment. 

PMID- 24939411
TI  - Clinical activity of a new regimen combining gemcitabine and alemtuzumab in high
      risk relapsed/refractory chronic lymphocytic leukemia patients.
AB  - Optimal treatment strategies are lacking in relapsed/refractory (R/R) chronic
      lymphocytic leukemia (CLL). Gemcitabine has shown activity and acceptable safety
      profile in B-cell lymphomas. We present a retrospective case review of
      gemcitabine and alemtuzumab, every 21 d (for up to six courses) in 27 community
      based patients with high-risk R/R CLL. Median age was 70 yr (44-83 yr), 55%
      patients had Binet stage C, deletion 17p (del(17p)) and/or deletion 11q
      (del(11q)) were found in 65% and 27%, bulky disease in 55.5%, and fludarabine
      refractoriness in 48% of cases, respectively. Overall response rate was 63%
      (29.6% clinical CR and 33.4% PR). At a median follow-up of 31 months, median PFS
      and OS were 15.4 and 24 months. In multivariate analysis, median OS is influenced
      by prior lines of treatment = 3 and bulky disease. Combination of alemtuzumab and
      gemcitabine appears to be an active, easy to administrate treatment in routine
      practice, high-risk R/R CLL patients.

PMID- 24939412
TI  - Regional differences in the fescue toxicosis response of Bos taurus cattle.
AB  - Cattle of the same breed from different regions of the USA may have altered
      responses to heat stress and fescue toxicosis. Angus steers from Missouri (MO
      ANG, n = 10, 513.6 +/- 13.6 kg BW) and Oklahoma (OK ANG, n = 10, 552.8 +/- 12.0
      kg BW) were fed a diet containing either endophyte-infected (E+, 30 MUg
      ergovaline/kg BW/day) or endophyte-uninfected (E-, 0 MUg ergovaline/kg BW/day)
      tall fescue seed for 23 days. Diet treatment began on day 2. Animals were
      maintained at thermoneutrality (TN, 19-22  degrees C, days 1-8) and then exposed
      to heat stress (HS, cycling 26-36  degrees C, days 9-22). On day 23, ambient
      temperature was returned to TN and used as a recovery day. Feed intake (FI) was
      measured daily, with rectal and skin temperatures determined six times daily.
      Feed intake reduction from pretreatment levels was greater (P < 0.01) for E +
      (13.9 +/- 0.9 versus 11.9 +/- 0.3 kg/day) compared to E - (12.6 +/- 0.9 versus
      12.4 +/- 0.3 kg/day) steers over the entire TN period, regardless of Angus group.
      During HS, E + cattle had reduced FI (P < 0.02; 6.9 +/- 0.2 versus 8.4 +/- 0.2
      kg/day) compared to E - animals, independent of region of origin. A greater
      decrease in FI (P < 0.01) was observed for OK (12.1 +/- 0.3 versus 6.2 +/- 0.2
      kg/day) compared to MO ANG (12.2 +/- 0.3 versus 7.9 +/- 0.2 kg/day) when ambient
      temperature was increased from TN to HS. On day 13 and days 15-22, OK ANG (E+)
      had reduced FI (P < 0.01, -2.21 kg) compared to OK ANG (E-), while there was no
      effect on MO ANG. From day 12 to day 22 of HS, daily minimum temperatures for
      ear, rump, and tail skin were less for E + (P < 0.05) when compared with E
      treated steers, signifying peripheral vasoconstriction in E + animals. This was
      supported by reduced shoulder and lower tail temperatures (P < 0.01) for E +
      compared to E-treated OK ANG on the recovery day. In summary, regional
      differences in the response to fescue toxicosis exist, with peripheral vasomotor
      effects becoming most evident when animals are subjected to rapid changes in
      their environment.

PMID- 24939413
TI  - Beginning of the end for universal healthcare in Australia?

PMID- 24939414
TI  - Temporal scaling in information propagation.
AB  - For the study of information propagation, one fundamental problem is uncovering
      universal laws governing the dynamics of information propagation. This problem,
      from the microscopic perspective, is formulated as estimating the propagation
      probability that a piece of information propagates from one individual to
      another. Such a propagation probability generally depends on two major classes of
      factors: the intrinsic attractiveness of information and the interactions between
      individuals. Despite the fact that the temporal effect of attractiveness is
      widely studied, temporal laws underlying individual interactions remain unclear,
      causing inaccurate prediction of information propagation on evolving social
      networks. In this report, we empirically study the dynamics of information
      propagation, using the dataset from a population-scale social media website. We
      discover a temporal scaling in information propagation: the probability a message
      propagates between two individuals decays with the length of time latency since
      their latest interaction, obeying a power-law rule. Leveraging the scaling law,
      we further propose a temporal model to estimate future propagation probabilities
      between individuals, reducing the error rate of information propagation
      prediction from 6.7% to 2.6% and improving viral marketing with 9.7% incremental
      customers. 

PMID- 24939415
TI  - Involvement of macrophage migration inhibitory factor and its receptor (CD74) in
      human breast cancer.
AB  - Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be
      involved in tumorigenesis. We evaluated, by immunohistochemical staining, the
      tissue expression and distribution of MIF and CD74 in serial sections of human
      invasive breast cancer tumor specimens. The serum MIF level was also determined
      in breast cancer patients. We showed a significant increase in serum MIF average
      levels in breast cancer patients compared to healthy individuals. MIF tissue
      expression, quantified by a modified Allred score, was strongly increased in
      carcinoma compared to tumor-free specimens, in the cancer cells and in the
      peritumoral stroma, with fibroblasts the most intensely stained. We did not find
      any significant correlation with histoprognostic factors, except for a
      significant inverse correlation between tumor size and MIF stromal positivity.
      CD74 staining was heterogeneous and significantly decreased in cancer cells but
      increased in the surrounding stroma, namely in lymphocytes, macrophages and
      vessel endothelium. There was no significant variation according to classical
      histoprognostic factors, except that CD74 stromal expression was significantly
      correlated with triple-negative receptor (TRN) status and the absence of estrogen
      receptors. In conclusion, our data support the concept of a functional role of
      MIF in human breast cancer. In addition to auto- and paracrine effects on cancer
      cells, MIF could contribute to shape the tumor microenvironment leading to
      immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors
      in a therapeutic perspective remains an attractive but complex challenge. Level
      of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti
      angiogenic drugs, particularly in TRN breast cancer tumor. 

PMID- 24939416
TI  - CYP1A1 Ile462Val polymorphism and colorectal cancer risk in Polish patients.
AB  - Colorectal cancer (CRC) is an epidemiological problem of a great importance in
      Poland; each year approximately 14,600 new cases of the disease are diagnosed.
      Mortality associated with CRC reaches approximately 10,400 cases per year
      (according to the National Cancer Registry). The 5-year survival rate is
      approximately 25 %, which is one of the lowest rates in Europe. The etiology of
      sporadic colorectal cancer (CRC) is multifactorial and has been attributed to an
      interplay between both environmental and genetic risk factors. In addition, there
      is a general consensus that genetic factors may modulate the influence of
      environmental insults. Following these assumptions, we performed a study on
      widely described polymorphisms in xenobiotic-metabolizing enzymes and DNA repair
      genes which may influence individual susceptibility to cancer. We selected five
      candidate polymorphisms in following genes: ERCC1 Asp118Asn (rs11615), XPC i11C/A
      (rs2279017), XRCC3 Met241Thr (rs861539) CYP1A1 Ile462Val (rs1048943) and NAT2
      A803G (rs1208) and assessed the importance of chosen SNPs on groups consisting of
      478 CRC patients and 404 controls. Only CYP1A1 Ile462Val was statistically
      significant in CRC patients over 50 years old: OR 2.05 (1.29-3.28); p = 1.25E-02
      and this association was more pronounced in the female group of CRC patients
      after the age of 50: OR 2.72 (1.43-5.14); p = 1.14E-02.

PMID- 24939418
TI  - Arsenic trioxide and bortezomib interact synergistically to induce apoptosis in
      chronic myelogenous leukemia cells resistant to imatinib mesylate through Bcr/Abl
      dependent mechanisms.
AB  - Arsenic trioxide (As2O3) and the proteasome inhibitor bortezomib (BTZ) have been
      used successfully to treat acute promyelocytic leukemia and multiple myeloma.
      Their synergistic effects with other anticancer drugs have been widely studied.
      In this study, interactions between As2O3 and BTZ were examined in imatinib
      resistant Bcr/Abl+ (K562r) cells. Co-treatment of K562r cells with subtoxic
      concentrations of As2O3 (2 uM) and BTZ (24 nM) resulted in a synergistic
      enhancement in growth inhibition and apoptosis, as demonstrated by increased
      annexin V staining. These events were associated with activation of protein
      kinase Cdelta, poly ADP-ribose polymerase cleavage and caspase-3 activation,
      along with downregulation of Bcr/Abl mRNA and Bcr/Abl protein expression levels
      during apoptosis. In addition, reactive oxygen species were downregulated during
      combined treatment in K562r cells. Collectively, these findings suggest that BTZ
      and As2O3 act synergistically to induce apoptosis in K562r cells. Therefore,
      further studies are required to assess the potential of BTZ and As2O3 combinatory
      treatment of chronic myeloid leukemia, particularly using imatinib-resistant
      Bcr/Abl+ clones.

PMID- 24939417
TI  - Longitudinal examination of decision-making performance in anorexia nervosa:
      before and after weight restoration.
AB  - BACKGROUND: This study aimed to extend previous work on decision-making deficits
      in anorexia nervosa (AN) by using a longitudinal design to examine decision
      making before and after weight restoration. METHODS: Participants were 22 women
      with AN and 20 healthy comparison participants who completed the Iowa Gambling
      Task (IGT). Decision-making was assessed both before and after weight restoration
      in a subset of 14 AN patients. Self-report and interview assessments were used to
      measure psychological correlates of decision-making performance including
      depression, anxiety, and eating disorder symptoms, and magnetic resonance imaging
      (MRI) scans were conducted to explore associations between brain volume in the
      orbitofrontal cortex (OFC) and decision-making in individuals with AN. RESULTS:
      Currently ill AN patients performed worse on the IGT compared to the control
      group. Although decision-making performance did not improve significantly with
      weight restoration in the full AN sample, AN patients who were poor performers at
      baseline did improve task performance with weight-restoration. When actively ill,
      lower body mass index (BMI) and decreased left medial OFC volume were
      significantly associated with worse IGT performance, and these associations were
      no longer significant after weight restoration. CONCLUSIONS: Findings suggest
      that decision-making deficits in AN in the acute phase of illness are associated
      with low weight and decreased left medial OFC volume, but increases in brain
      volume and BMI may not have been sufficient to improve decision-making in all
      patients. Findings contribute to a model for understanding how some patients may
      sustain self-starvation, and future work should examine whether decision-making
      deficits predict relapse.

PMID- 24939419
TI  - Translating curcumin to the clinic for lung cancer prevention: evaluation of the
      preclinical evidence for its utility in primary, secondary, and tertiary
      prevention strategies.
AB  - Lung cancer is responsible for over one million deaths worldwide each year.
      Smoking cessation for lung cancer prevention remains key, but it is increasingly
      acknowledged that prevention strategies also need to focus on high-risk groups,
      including ex-smokers, and patients who have undergone resection of a primary
      tumor. Models for chemoprevention of lung cancer often present conflicting
      results, making rational design of lung cancer chemoprevention trials
      challenging. There has been much focus on use of dietary bioactive compounds in
      lung cancer prevention strategies, primarily due to their favorable toxicity
      profile and long history of use within the human populace. One such compound is
      curcumin, derived from the spice turmeric. This review summarizes and stratifies
      preclinical evidence for chemopreventive efficacy of curcumin in models of lung
      cancer, and adjudges the weight of evidence for use of curcumin in lung cancer
      chemoprevention strategies. 

PMID- 24939420
TI  - RhoA/phosphatidylinositol 3-kinase/protein kinase B/mitogen-activated protein
      kinase signaling after growth arrest-specific protein 6/mer receptor tyrosine
      kinase engagement promotes epithelial cell growth and wound repair via
      upregulation of hepatocyte growth factor in macrophages.
AB  - Growth arrest-specific protein 6 (Gas6)/Mer receptor tyrosine kinase (Mer)
      signaling modulates cytokine secretion and helps to regulate the immune response
      and apoptotic cell clearance. Signaling pathways that activate an epithelial
      growth program in macrophages are still poorly defined. We report that
      Gas6/Mer/RhoA signaling can induce the production of epithelial growth factor
      hepatic growth factor (HGF) in macrophages, which ultimately promotes epithelial
      cell proliferation and wound repair. The RhoA/protein kinase B (Akt)/mitogen
      activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal
      regulated protein kinase, and Jun NH2-terminal kinase axis in RAW 264.7 cells,
      was identified as Gas6/Mer downstream signaling pathway for the upregulation of
      HGF mRNA and protein. Conditioned medium from RAW 264.7 cells that had been
      exposed to Gas6 or apoptotic cells enhanced epithelial cell proliferation of the
      epithelial cell line LA-4 and wound closure. Cotreatment with an HGF receptor
      blocking antibody or c-Met antagonist downregulated this enhancement. Inhibition
      of Mer with small interfering RNA (siRNA) or the RhoA/Rho kinase pathway by RhoA
      siRNA or Rho kinase pharmacologic inhibitor suppressed Gas6-induced HGF mRNA and
      protein expression in macrophages and blocked epithelial cell proliferation and
      wound closure induced by the conditioned medium. Our data provide evidence that
      macrophages can be reprogrammed by Gas6 to promote epithelial proliferation and
      wound repair via HGF, which is induced by the Mer/RhoA/Akt/MAP kinase pathway.
      Thus, defects in Gas6/Mer/RhoA signaling in macrophages may delay tissue repair
      after injury to the alveolar epithelium. 

PMID- 24939421
TI  - Vimocin and vidapin, cyclic KTS peptides, are dual antagonists of
      alpha1beta1/alpha2beta1 integrins with antiangiogenic activity.
AB  - Obtustatin and viperistatin, members of the disintegrin protein family, served as
      lead compounds for the synthesis of linear and cyclic peptides containing the KTS
      binding motif. The most active linear peptide, a viperistatin analog, indicated
      the importance of Cys(19) and Cys(29), as well as the presence of Arg at position
      24 for their biologic activity, and was used as the basic sequence for the
      synthesis of cyclic peptides. Vimocin (compound 6) and vidapin (compound 10)
      showed a high potency (IC50 = 0.17 nM) and intermediate efficacy (20 and 40%) in
      inhibition of adhesion of alpha1/alpha2 integrin overexpressor cells to
      respective collagens. Vimocin was more active in inhibition of the wound healing
      (53%) and corneal micropocket (17%) vascularization, whereas vidapin was more
      potent in inhibition of migration in the Matrigel tube formation assay (90%).
      Both compounds similarly inhibited proliferation (50-90%) of endothelial cells,
      and angiogenesis induced by vascular endothelial growth factor (80%) and glioma
      (55%) in the chorioallantoic membrane assay. These peptides were not toxic to
      endothelial cell cultures and caused no acute toxicity upon intravenous injection
      in mice, and were stable for 10-30 hours in human serum. The in vitro and in vivo
      potency of the peptides are consistent with conformational ensembles and
      "bioactive" space shared by obtustatin and viperistatin. These findings suggest
      that vimocin and vidapin can serve as dual alpha1beta1/alpha2beta1 integrin
      antagonists in antiangiogenesis and cancer therapy. 

PMID- 24939423
TI  - Microbiological isolates and antibiotic sensitivities in culture-proven
      endophthalmitis: a 15-year review.
AB  - BACKGROUND: To describe the microbiological spectrum and antibiotic sensitivities
      of organisms causing culture-proven endophthalmitis in Queensland, Australia, and
      to compare results with similar studies from other parts of Australia and other
      countries. METHODS: A retrospective, multicentre, non-comparative, consecutive
      case series. Public hospital microbiology records from culture-positive
      endophthalmitis cases were reviewed over 15 years from June 1998 to June 2013.
      Outcome measures were type of endophthalmitis, vitreous isolates cultured and
      antibiotic sensitivities. RESULTS: 205 cases of culture-proven endophthalmitis
      were identified with a total of 229 isolates cultured. The most common organisms
      isolated were Staphylococcus epidermidis in 23.1%, Coagulase-negative
      Staphylococcus in 12.7%, Streptococcus viridans group in 10.0%, Candida species
      in 6.1%, fungal mold species in 5.7%. For gram-positive organisms, sensitivities
      were vancomycin 100%, cephazolin 79% and penicillin 47%. For gram-negative
      organisms, sensitivities were ceftazidime 100%, amikacin 100%, ciprofloxacin 100%
      and gentamicin 95.5%. For fungal isolates, sensitivities were voriconazole 93%,
      ketoconazole 89%, caspofungin 70% and amphotericin B 58%. CONCLUSIONS: The
      microbiological spectrum and antibiotic sensitivities of endophthalmitis cases in
      Queensland, Australia, is similar to the spectrum of organisms causing
      endophthalmitis in other parts of Australia, North America and Europe. Empirical
      intravitreal vancomycin, ceftazidime and voriconazole are the most appropriate
      empirical antibiotics for suspected infective endophthalmitis.

PMID- 24939422
TI  - Changes in subfoveal choroidal thickness associated with uveitis activity in
      patients with Behcet's disease.
AB  - AIMS: To evaluate the efficacy of measuring subfoveal choroidal thickness in
      monitoring uveitis activity before and after treatment with infliximab in
      patients with Behcet's disease (BD)-associated uveitis. METHODS: Thirteen
      patients with BD (23 eyes) were selected for this retrospective observational
      case study. Subfoveal choroidal thickness was measured during active and
      remission phases of uveitis by enhanced depth imaging-spectral domain optical
      coherence tomography (EDI-OCT). In five patients (10 eyes), choroidal thickness
      was assessed at weeks 0, 2, 6 and 14 after the initiation of infliximab
      treatment. RESULTS: Accompanied by excessive dye leakage from choroidal vessels
      on indocyanine green angiography, dilation of choroidal vessels was observed in
      the active phase of uveitis by EDI-OCT and the choroidal thickness was
      significantly greater than that in the remission phase. Treatment with infliximab
      significantly reduced the choroidal thickness from week 2 after the first
      infusion, and the reduced choroidal thickness was maintained thereafter. No
      correlation was found between choroidal thickness and best corrected visual
      acuity converted to logarithm of the minimum angle of resolution, but choroidal
      thickness correlated significantly with anterior and posterior ocular
      inflammation scores. CONCLUSIONS: This study indicates that measurement of
      subfoveal choroidal thickness by EDI-OCT is useful for evaluating the activity of
      uveitis and the therapeutic efficacy in patients with BD.

PMID- 24939424
TI  - Orbital cellulitis in Scotland: current incidence, aetiology, management and
      outcomes.
AB  - PURPOSE: Orbital cellulitis is a potentially blinding and life-threatening
      condition. There are little published data on the incidence of orbital cellulitis
      and little is known about the differences between children and adults affected.
      The purpose of this study was to identify the incidence, aetiology, management
      and outcome of orbital cellulitis in children and adults in Scotland. METHODS:
      This study was a 1-year prospective observational study using the Scottish
      Ophthalmic Surveillance Unit reporting system among Scottish ophthalmologists.
      RESULTS: The response rate from ophthalmologists was 66.4%. There were 15
      children and 5 adults reported giving an incidence of 1.6 per 100 000 and 0.1 per
      100 000 in children and adults, respectively. 47% of children had a preceding
      upper respiratory tract infection with 87% having radiological evidence of sinus
      disease. Within the adult group, there was preceding immunosuppression and
      trauma. Streptococcus (66%) and Haemophilus (46%) species were the most commonly
      isolated pathogens in children. Respiratory pathogens were less predictable in
      adults. All patients were treated with intravenous antibiotics. All children with
      orbital and subperiosteal abscesses had surgery; one adult with orbital abscess
      did not have surgery. There were two cases of series morbidity: one intracranial
      spread of infection and one evisceration. DISCUSSION: The incidence of orbital
      cellulitis is higher in children than in adults. In children, it commonly follows
      upper respiratory infection and sinus disease; however, in adults, preceding
      illness and trauma are more common. Respiratory pathogens are common in affected
      children. Intravenous antibiotics and surgical treatment of abscesses remain the
      preferred management.

PMID- 24939425
TI  - Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food
      intake.
AB  - Obesity is a growing epidemic, and current medical therapies have proven
      inadequate. Endogenous satiety hormones provide an attractive target for the
      development of drugs that aim to cause effective weight loss with minimal side
      effects. Both glucagon and GLP-1 reduce appetite and cause weight loss.
      Additionally, glucagon increases energy expenditure. We hypothesized that the
      combination of both peptides, administered at doses that are individually
      subanorectic, would reduce appetite, while GLP-1 would protect against the
      hyperglycemic effect of glucagon. In this double-blind crossover study,
      subanorectic doses of each peptide alone, both peptides in combination, or
      placebo was infused into 13 human volunteers for 120 min. An ad libitum meal was
      provided after 90 min, and calorie intake determined. Resting energy expenditure
      was measured by indirect calorimetry at baseline and during infusion. Glucagon or
      GLP-1, given individually at subanorectic doses, did not significantly reduce
      food intake. Coinfusion at the same doses led to a significant reduction in food
      intake of 13%. Furthermore, the addition of GLP-1 protected against glucagon
      induced hyperglycemia, and an increase in energy expenditure of 53 kcal/day was
      seen on coinfusion. These observations support the concept of GLP-1 and glucagon
      dual agonism as a possible treatment for obesity and diabetes. 

PMID- 24939427
TI  - Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian
      influenza virus infections.
AB  - Melanoma differentiation-associated gene 5 (MDA5) is an important intracellular
      receptor that recognizes long molecules of viral double-stranded RNA in innate
      immunity. To understand the mechanism of duck MDA5-mediated innate immunity, we
      cloned the MDA5 cDNA from the Muscovy duck (Cairina moschata). Quantitative real
      time PCR analysis indicates that duck MDA5 mRNA was constitutively expressed in
      all sampled tissues. A significant increase of MDA5 mRNA was detected in the
      brain, spleen and lungs of ducks after infection with an H5N1 highly pathogenic
      avian influenza virus (HPAIV). We investigated the role of the predicted
      functional domains of MDA5. The results indicate the caspase activation and
      recruitment domain (CARD) of duck MDA5 had a signal transmission function through
      IRF-7-dependent signaling pathway. Overexpression of the CARD strongly activated
      the chicken IFN-beta promoter and upregulated the mRNA expression of antiviral
      molecules (such as OAS, PKR and Mx), proinflammatory cytokines (such as IL-2, IL
      6, IFN-alpha and IFN-gamma, but not IL-1beta and IL-8) and retinoic acid
      inducible gene I (RIG-I)-like receptors (RLR) (RIG-I and LGP2) without exogenous
      stimulation. We also demonstrate the NS1 of the H5N1 HPAIV inhibited the duck
      MDA5-mediated signaling pathway in vitro. These results suggest that duck MDA5 is
      an important receptor for inducing antiviral activity in the host immune response
      of ducks.

PMID- 24939426
TI  - Blood and islet phenotypes indicate immunological heterogeneity in type 1
      diabetes.
AB  - Studies in type 1 diabetes indicate potential disease heterogeneity, notably in
      the rate of beta-cell loss, responsiveness to immunotherapies, and, in limited
      studies, islet pathology. We sought evidence for different immunological
      phenotypes using two approaches. First, we defined blood autoimmune response
      phenotypes by combinatorial, multiparameter analysis of autoantibodies and
      autoreactive T-cell responses in 33 children/adolescents with newly diagnosed
      diabetes. Multidimensional cluster analysis showed two equal-sized patient
      agglomerations characterized by proinflammatory (interferon-gamma-positive,
      multiautoantibody-positive) and partially regulated (interleukin-10-positive,
      pauci-autoantibody-positive) responses. Multiautoantibody-positive nondiabetic
      siblings at high risk of disease progression showed similar clustering.
      Additionally, pancreas samples obtained post mortem from a separate cohort of 21
      children/adolescents with recently diagnosed type 1 diabetes were examined
      immunohistologically. This revealed two distinct types of insulitic lesions
      distinguishable by the degree of cellular infiltrate and presence of B cells that
      we termed "hyper-immune CD20Hi" and "pauci-immune CD20Lo." Of note, subjects had
      only one infiltration phenotype and were partitioned by this into two equal-sized
      groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi
      subjects being 5 years younger. These data indicate potentially related islet and
      blood autoimmune response phenotypes that coincide with and precede disease. We
      conclude that different immunopathological processes (endotypes) may underlie
      type 1 diabetes, carrying important implications for treatment and prevention
      strategies. 

PMID- 24939429
TI  - Electrochemical impedance spectroscopy study on polymerization of L-lysine on
      electrode surface and its application for immobilization and detection of
      suspension cells.
AB  - Poly-L-lysine (PLL), which has been employed as a conductive polymer in the
      construction of some electrochemical sensors, can be prepared using L-lysine by
      cyclic voltammetry (CV) with a wide potential range. However, the presented
      explanation and description about its polymerization mechanism seems
      oversimplified because the self-reaction of electrode and the electrolysis of
      solvent at high potential are ignored. This work presents an intensive
      investigation on the relevant reactions during the process of PLL-polymerization
      using CV, X-ray photoelectron spectroscopy, Fourier transform-infrared
      spectroscopy, and electrochemical impedance spectroscopy. At a higher positive
      potential, the transfer from lysine molecules to cation radicals and the
      polymerization reaction on the glassy carbon electrode (GCE) could be achieved,
      accompanied by the activation of GCE, the formation of oxygen-containing
      functional groups, and the generation of oxygen derived from the oxidation of
      water. The adsorbed oxygen had a seriously negative effect on the formation of
      PLL unless it suffered reduction at a lower negative potential. The charge
      transfer through the electrochemical polymerized PLL film was seriously hindered
      by the immobilization of suspension cells due to the electrostatic interaction.
      The charge-transfer resistance difference (DeltaR(ct)) was increased with the
      enhancement of the cell number (N(cells)) and the 1/DeltaR(ct) value displayed a
      linear response with 1/N(cells) in the range of 5.0 * 10(2)-1.0 * 10(5) cells
      with a detection limit of 180 cells estimated at a signal-to-noise ratio of 3. A
      sensitive electrochemical sensor for the quantitative detection of suspension
      cells was developed.

PMID- 24939428
TI  - Extremely low-frequency magnetic field exposure, electrical shocks and risk of
      Parkinson's disease.
AB  - PURPOSE: Previous studies did not provide strong evidence for an increased
      Parkinson's disease (PD) risk after exposure to extremely low-frequency magnetic
      fields (ELF-MF), but were limited in their scope to address other exposures
      related to the use of electricity such as electrical shocks. We evaluated the
      associations of PD with exposure to ELF-MF, electrical shocks and having worked
      in "electrical occupations." METHODS: We conducted a hospital-based case-control
      study, including 444 PD patients and 876 age- and sex-matched controls.
      Occupational histories were collected in telephone interviews and were linked to
      job-exposure matrices on ELF-MF exposure and on electrical shocks. In addition,
      questions on use of household appliances involving ELF-MF exposure, experienced
      electrical shocks and potential confounders were asked. RESULTS: No association
      of PD risk with any of the evaluated exposures related to electricity was
      observed. We did, however, observe quite consistently reduced risk estimates
      across the majority of the exposure categories explored. Given the results of the
      previous studies and the absence of any postulated mechanism, this is unlikely to
      represent a true protective effect of ELF-MF or electrical shocks on the
      occurrence of PD. CONCLUSIONS: The results of this study suggest that no
      association exists between PD and exposure to ELF-MF, electrical shocks or having
      worked in "electrical occupations."

PMID- 24939430
TI  - GAD autoantibody affinity in schoolchildren from the general population.
AB  - AIMS/HYPOTHESIS: Subtyping GAD autoantibody (GADA) responses using affinity
      measurement allows the identification of GADA-positive children with a family
      history of type 1 diabetes who are at risk of developing diabetes. Here, we asked
      whether GADA affinity is a useful marker to stratify the risk of type 1 diabetes
      in GADA-positive schoolchildren from the general population. METHODS: GADA
      affinity was measured by competitive binding experiments with [(125)I]-labelled
      and unlabelled human 65 kDa isoform of GAD (GAD65) in sera from 97 GADA-positive
      children identified in the Karlsburg Type 1 Diabetes Risk Study of a general
      schoolchild population in north-eastern Germany. GADA epitope specificity was
      determined using radiobinding assays with [(35)S]-labelled GAD65/67 kDa isoform
      of GAD (GAD67) chimeric proteins. RESULTS: GADA affinity was high, >= 10(10)
      l/mol, in 33 of 35 multiple islet autoantibody-positive children. In contrast,
      the affinity ranged widely among 62 single GADA-positive children (median 3.1 *
      10(9) l/mol; range 5.6 * 10(6) to >4.0 * 10(11) l/mol; p < 0.0001). High-affinity
      GADA were associated with HLA-DRB1*03 (p = 0.02) and predominantly directed
      against the C-terminal and/or middle part of the GAD65 protein. At follow-up, the
      affinity remained relatively constant. Five of the single GADA-positive children
      developed additional islet autoantibodies and had high-affinity GADA. Twenty-six
      children progressed to type 1 diabetes; among them, 23 had GADA affinities of >=
      10(10) l/mol before disease onset. CONCLUSIONS/INTERPRETATION: Schoolchildren
      from the general population may develop heterogeneous GADA responses, and a high
      affinity can identify those GADA-positive children who are more likely to
      progress to type 1 diabetes.

PMID- 24939431
TI  - Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its
      activity is decreased in human islets from individuals with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Inhibition of the enzyme dipeptidyl peptidase 4 (DPP-4), which
      cleaves and inactivates glucagon-like peptide 1 (GLP-1), is a glucose-lowering
      strategy in type 2 diabetes. Since DPP-4 is a ubiquitously distributed enzyme, we
      examined whether it is expressed in islets and whether an islet effect to inhibit
      DPP-4 may result in stimulated insulin secretion. METHODS: We investigated DPP-4
      expression and activity in the islets of mouse models of obesity as well as human
      islets from non-diabetic and type 2 diabetic donors. We further investigated
      whether inhibition with DPP-4 inhibitors could promote insulin secretion via
      islet GLP-1 in isolated islets. RESULTS: DPP-4 was readily detected in mouse and
      human islets with species-specific cellular localisation. In mice, DPP-4 was
      expressed predominantly in beta cells, whereas in humans it was expressed nearly
      exclusively in alpha cells. DPP-4 activity was significantly increased in islets
      from diet-induced obese mice compared with mice fed a control diet. In humans,
      DPP-4 activity was significantly lower in islets from type 2 diabetic donors than
      in non-diabetic donors. In human islets, there was a significant positive
      correlation between DPP-4 activity and insulin secretory response to 16.7 mmol/l
      glucose. Treatment of mouse islets with the DPP-4 inhibitors, NVPDPP728 and
      vildagliptin, resulted in a significant potentiation of insulin secretion in a
      GLP-1-dependent manner, as this was inhibited by the GLP-1 receptor antagonist,
      Exendin (9-39), and was retained in glucose-dependent insulinotropic polypeptide
      (GIP) receptor-deficient mice but lost in mice lacking GLP-1 receptors or both
      incretin receptors. Human islets treated with the DPP-4 inhibitor, vildagliptin,
      showed increased secretion of insulin and intact GLP-1.
      CONCLUSIONS/INTERPRETATION: We conclude that DPP-4 is present and active in mouse
      and human islets, is regulated by the disease state, and that inhibition of islet
      DPP-4 activity can have direct effects on islet function. Inhibiting islet DPP-4
      activity may therefore contribute to the insulin-secretory and glucose-lowering
      action of DPP-4 inhibition.

PMID- 24939432
TI  - Valproate improves memory deficits in an Alzheimer's disease mouse model:
      investigation of possible mechanisms of action.
AB  - Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder
      affecting the learning and memory abilities in the brain. Key findings from
      recent studies of epigenetic mechanisms of memory suggest chromatin remodeling
      disorders via histone hypoacetylation of the lysine residue contribute to the
      cognitive impairment in AD. Therefore, the deinhibition of histone acetylation
      induced by histone deacetylases (HDACs) inhibitors contributes to recovery of
      learning and memory. We show here that the antiepileptic drug sodium valproate
      (VPA) potently enhanced long-term recognition memory and spatial learning and
      memory in AD transgenic mice. Possible mechanisms showed VPA could significantly
      elevate histone acetylation through HDACs activity inhibition and increase
      plasticity-associated gene expression within the hippocampi of mice. Our study
      suggests that VPA, serving as a HDACs inhibitor, can be considered as a potential
      pharmaceutical agent for the improvement of cognitive function in AD.

PMID- 24939433
TI  - Large inter-individual variation in isoflavone plasma concentration limits use of
      isoflavone intake data for risk assessment.
AB  - BACKGROUND/OBJECTIVES: Isoflavones are present in soy foods and soy-based
      supplements. Despite low plasma isoflavone concentrations in the general Western
      population, concentrations in supplement users exceed those suggested to be
      beneficial for health in Asian populations, raising concerns for adverse effects.
      To aid risk assessment, quantification of the relation between isoflavone intake
      and plasma concentrations is essential. SUBJECTS/METHODS: Plasma samples were
      collected from postmenopausal women in three placebo-controlled crossover studies
      with 8-week periods for supplements (two studies, ~100 mg isoflavones/day, n=88)
      or 4-week periods for soy foods (one study, ~48 mg isoflavones/day, n=15). Plasma
      isoflavone concentrations (daidzein, equol, genistein and glycitein) were
      quantified using high-performance liquid chromatography and electrochemical
      detection. The association between plasma concentrations and isoflavone intake,
      equol producer status, intake-producer interaction and background dietary intake
      was assessed based on the assumption of a log-linear relation. RESULTS: Median
      plasma total isoflavone concentrations after the soy food and supplement
      interventions were respectively 2.16 and 3.47 MUmol/l for equol producers and
      1.30 and 2.39 MUmol/l for non-producers. Regression analysis showed that doubling
      isoflavone intake increased plasma concentrations by 55-62% (+/-s.e. 1-2%,
      R(2)>0.87) for daidzein, genistein, equol (only for producers) and total
      isoflavones; for glycitein the association was weaker (15+/-1%, R(2)=0.48).
      Adjustments for energy, carbohydrate and fat intake did not affect these
      estimates. Inter-individual variation, estimated based on repeated measures in
      one of the studies, was 30-96%. CONCLUSIONS: Although the relation between
      isoflavone intake and plasma concentrations was adequately quantified, the use of
      isoflavone intake data for risk assessment needs caution due to large inter
      individual variation in plasma concentrations.

PMID- 24939434
TI  - Primary epiploic appendagitis and fructose malabsorption.
AB  - Primary epiploic appendagitis (PEA) is a rare cause of abdominal acute or
      subacute complaints. Diagnosis of PEA is made when computed tomography (CT)
      reveals a characteristic lesion. We report on contrast-enhanced CT images of a
      patient with PEA and regression of inflammation and the reduction in size of the
      inflamed appendage over the time period of 4 months. Patients with PEA usually
      recover without medication or surgical treatment within a few weeks. However, due
      to continuing bloating and irregular bowel movements we investigated carbohydrate
      malabsorption and diagnosed a fructose malabsorption. Bloating and irregular
      bowel movements in this patient with PEA were correlated to carbohydrate
      malabsorption and were treated successfully with a diet free of culprit
      carbohydrates. 

PMID- 24939435
TI  - Dietary magnesium intake is inversely associated with serum C-reactive protein
      levels: meta-analysis and systematic review.

PMID- 24939436
TI  - Dietary magnesium and inflammation.

PMID- 24939437
TI  - alpha-Tocopherol supplementation reduces biomarkers of oxidative stress in
      children with Down syndrome: a randomized controlled trial.
AB  - BACKGROUND: Down syndrome (DS) is the most common human chromosomal abnormality.
      It is characterized by mental retardation and several metabolic disturbances,
      including elevated oxidative stress, which may be causally linked. Treatment with
      dietary antioxidants has been suggested as a potential method to alleviate the
      oxidative damage and retardation of DS patients, but prior supplementation work
      has been equivocal. AIM: To evaluate the effects of supplementation with
      antioxidants alpha-tocopherol and alpha-lipoic acid (ALA) on oxidative stress
      biomarkers in DS children. METHODS: Ninety-three DS children aged 7-15 years from
      both sexes were randomly allocated to three groups: alpha-tocopherol (400
      IU/day), ALA (100 mg/day) and placebo. The intervention period was 4 months. A
      healthy control group consisted 26 non-DS siblings. Serum thiobarbituric acid
      reactive substances (TBARS) and urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) were
      used as biomarkers of oxidative stress. RESULTS: DS children had greater levels
      of baseline oxidative stress than their siblings. Moreover, males had greater
      levels of 8OHdG than females (P<0.001) but there was no significant association
      between age and biomarkers of oxidative stress. Serum levels of TBARS did not
      change significantly over time, or relative to placebo. Although urinary 8OHdG
      concentrations decreased significantly in both alpha-tocopherol and ALA, groups
      compared with the baseline levels (P<0.001), mean final levels of urinary 8OHdG
      concentrations differed significantly only between alpha-tocopherol and placebo
      groups (P<0.01). CONCLUSIONS: alpha-Tocopherol supplementation of the diets of DS
      children may attenuate oxidative stress at the DNA level.

PMID- 24939438
TI  - Qualitative research building real-life interventions: user-involving development
      of a mindfulness-based lifestyle change support program for overweight citizens.
AB  - BACKGROUND/OBJECTIVES: This study is an experiment of putting social sciences to
      work in developing a support intervention for healthy lifestyle changes that
      would be attractive and manageable in real-life settings. Starting with a
      hypothesis that a class of intervention methods based on an unconventional 'low
      tension' strategy may offer an effective support of stable, long-term changes
      well integrated in everyday life, difficult to maintain with conventional dieting
      and self-control approaches, this study focuses on designing and optimizing an
      intervention model combining several low-tension methods: mindfulness, small
      steps and group support. SUBJECTS/METHODS: In three consecutive 'action research'
      cycles, the intervention was run in practice with groups of 20 overweight or
      obese citizens. Qualitative data, mainly in the form of recorded group sessions
      and individual interviews with group participants and group leaders, were
      systematically collected and analyzed, using a framework of social psychological
      theory to focus on difficulties, resources and meanings connected with habits and
      everyday life. This information was recycled into the design process for the next
      version of the intervention. RESULTS: We describe the user-involving development
      processes toward a more attractive and manageable intervention model. The model
      now exists as a well-articulated package whose effectiveness is being tested in a
      randomized controlled trial study. CONCLUSIONS: Social science can be put to work
      in systematically integrating real-life experience in a development process. It
      answers a very different kind of question than clinical trials-filling another
      place in an overall research program to create useful knowledge of what helps-in
      complex, everyday, real life.

PMID- 24939439
TI  - The effects of soy protein on chronic kidney disease: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND/OBJECTIVES: There is a growing body of evidence to indicate that soy
      protein consumption may have a beneficial effect on kidney function. We performed
      a meta-analysis to evaluate the effects of soy protein consumption compared with
      animal protein consumption in patients with pre-dialysis chronic kidney disease
      (CKD). SUBJECTS/METHODS: We conducted a structured electronic search of the
      databases PubMed, EMBASE, Cochrane Library and Chinese Biological Medicine for
      randomized controlled trials published up to March 2014. The outcome measures
      were serum creatinine (SCR), triglyceride (TG), total cholesterol (TC), calcium
      (Ca) and phosphorus concentrations. Weighted or standard mean differences were
      calculated for net changes using random-effects models. RESULTS: The meta
      analysis consisted of nine trials, comprising 197 subjects. Soy protein intake
      significantly reduced SCR and serum phosphorus concentrations. The mean
      difference was -6.231 MUmol/l (95% confidence interval (CI): -11.109, -1.352
      MUmol/l) for SCR (P=0.012) and -0.804 (95% CI: -1.143, -0.464 MUmol/l) for serum
      phosphorus (P=0.00). It also significantly reduced serum TG, with a pooled
      estimated change of -0.223 mmol/l (95% CI: -0.396, -0.051 mmol/l; P=0.011) after
      the exclusion of one trial indicated by sensitivity analyses. No statistically
      significant effects were observed for TC (-0.135 mmol/l (95% CI: -0.289, 0.019
      mmol/l)) or Ca (0.023 mmol/l (95% CI: -0.016, 0.062 mmol/l)). CONCLUSIONS: The
      meta-analysis suggested a protective effect of soy protein consumption on SCR and
      serum phosphorus concentrations in pre-dialysis CKD patients. It may also have a
      significant effect on lowering serum TG concentrations. However, nonsignificant
      effects on TC and Ca were observed. Evidence was limited because of the
      relatively small number of available trials and subjects.

PMID- 24939442
TI  - Mucosal leishmaniasis with primary oral involvement: a case series and a review
      of the literature.
AB  - OBJECTIVE: To analyze retrospectively a case series of primary oral leishmaniasis
      and to review the literature on head-neck primary mucosal leishmaniasis (ML) in
      immunocompetent patients. SUBJECTS AND METHODS: A PUBMED search was carried out
      from 1950 to 2013. Clinical records of patients with primary head-neck mucosal
      manifestations of leishmaniasis were analyzed. In addition, clinical records
      between 2001 and 2012 of patients with primary oral manifestations were collected
      in two independent hospitals. RESULTS: Our multicenter case series revealed seven
      patients with oral leishmaniasis. The most commonly affected site was the tongue
      (four patients, 57%), and the most common clinical presentation was an exophytic
      lesion (six patients, 85%). The literature review showed 11 reports published
      between 2005 and 2013, describing 13 patients (100% male) affected by head-neck
      primary ML (54% laryngeal, 31% oral, 23% pharyngeal, and 15% endonasal). The most
      common clinical presentation was an exophytic lesion (69%). CONCLUSIONS: The
      literature analysis revealed that in immunocompetent patients, the oral mucosa is
      the second most frequently affected site of the head and neck region. In the oral
      cavity, the tongue is the most affected site. Diagnosis of oral leishmaniasis
      represents a challenge but must be considered in any differential diagnosis of
      exophytic lesions of oral mucosa.

PMID- 24939441
TI  - Brain activation in response to craving- and aversion-inducing cues related to
      alcohol in patients with alcohol dependence.
AB  - BACKGROUND: Episodes of alcohol consumption produce use-limiting aversive effects
      as well as use-promoting euphoric effects. The brain regions associated with the
      reward circuit in patients with alcohol dependence (PAD) show signs of
      conditioning for alcohol craving. Alternatively, brain structures in the medial
      temporal region are known to be crucial for aversive conditioning. In this study,
      we compare differences in patterns of brain activation in response to cues that
      induce cravings versus aversion in PAD. METHODS: Thirty-eight PAD and 26 healthy
      volunteers were administered cue reactivity tasks while undergoing functional
      magnetic resonance imaging (fMRI) to examine brain response to craving-inducing
      cues (CIC) and aversion-inducing cues (AIC). RESULTS: Activation of the right
      medial frontal gyrus (right orbitofrontal cortex) during CIC was greater in PAD
      than in healthy volunteers. Participants in the PAD group displayed less
      activation in the right amygdala and the right middle temporal gyrus during AIC
      than did the healthy volunteers. Brain reactivity within the right medial frontal
      gyrus in response to CIC was positively correlated with the scores of PAD on the
      Korean Alcohol Urge Questionnaire (AUQ-K) and the Michigan Alcohol Screening Test
      (MAST). Reactivity within the amygdala in response to AIC was negatively
      correlated with AUQ-K scores among PAD. CONCLUSION: The dysfunction of the
      orbitofrontal cortex that results from repeated exposure to alcohol accounts for
      craving and relapse in PAD. Additionally, PAD seem to be less sensitive to cues
      related to aversive consequences of alcohol overuse in comparison with healthy
      individuals.

PMID- 24939440
TI  - Parental psychopathology moderates the influence of parental divorce on lifetime
      alcohol use disorders among Israeli adults.
AB  - BACKGROUND: Parental divorce and psychopathology are well-documented risk factors
      for alcohol use disorders (AUD) in the United States and other countries where
      divorce is common and per capita total alcohol consumption is moderate to high.
      However, little is known about these relationships in countries where divorce and
      alcohol problems are less common, such as Israel. METHODS: Israeli adult
      household residents (N=797) age 21-45 were interviewed in person between 2007 and
      2009. Logistic regression models were used to examine main and additive
      interaction effects of parental divorce and psychopathology on lifetime DSM-IV
      AUD, adjusting for age, gender, and ethnicity. RESULTS: Parental divorce
      (OR=2.18, p<=0.001) and parental psychopathology (OR=1.61, p<=0.01) were
      independently associated with lifetime AUD and, when considered together, showed
      significant interaction (p=0.026). Specifically, the effect of divorce on AUD was
      only significant among those who also reported parental psychopathology.
      CONCLUSIONS: This is the first study showing the influence of parental divorce
      and psychopathology on risk for AUD among Israeli adults, where both divorce and
      AUD are less common than in the United States. Alcohol prevention and treatment
      professionals should recognize that children who experience parental divorce
      and/or psychopathology could be more vulnerable to later developing AUD than
      those whose parents remain together and without psychopathology.

PMID- 24939445
TI  - A successful case of pushing, catching, and fixing a migrated microcoil using a
      detachable coil.

PMID- 24939444
TI  - Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6
      hydroxydopamine-induced rat model.
AB  - The purpose of this study was to determine the effectiveness of the systemic
      administration of high dose erythropoietin (EPO) in a 6-hydroxydopamine (6-OHDA)-
      induced rat model. Rats were divided into 7 groups. Groups 1-4 were administered
      daily EPO doses of 0; 2,500; 5,000 and 10,000 U/kg via intraperitoneal injection
      (i.p.) for 5 days. The EPO concentration in cerebrospinal fluid (CSF) was
      determined by enzyme-linked immunosorbent assay (ELISA) and western blot
      analysis. The dose of 10,000 U/kg was then selected for subsequent experiments.
      In group 5, rats received saline via medial forebrain bundle (MFB). In group 6,
      rats received 6-OHDA via MFB. In group 7, an EPO concentration of 10,000 U/kg was
      constantly administered i.p. for 5 days to rats prior to 6-OHDA injection via
      MFB. Behavioral analysis was performed for groups 5-7 by rat rotation tests. The
      number of tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra
      (SN) was measured by immuno-cyto-chemistry. The activation of c-Jun N-terminal
      kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated
      protein kinases (MAPKs) and caspase-3 signaling in rats were analyzed using
      western blotting. The results showed that there was a significant increase in EPO
      levels in the CSF in 10,000 U/kg group compared with the 2,500 and 5,000 U/kg
      groups (P<0.01). Significantly fewer rotational counts were obtained in rats that
      were pretreated with EPO compared with saline-pretreated 6-OHDA-lesioned rats
      (P<0.001). The dopaminergic neurons in the 6-OHDA-lesioned SN were also increased
      in the EPO-pretreated rats when compared with control rats (P<0.01). Western blot
      analysis revealed that EPO inhibited the 6-OHDA-induced activation of JNK, ERK,
      p38 MAPK and caspase-3 signaling in the rat model. In conclusion, systemic
      administration of a high dose of EPO exerted neuroprotective effects in reversing
      behavioral deficits associated with Parkinson's disease and prevented loss of the
      dopaminergic neurons through the MAPK pathway.

PMID- 24939446
TI  - Localized amyloidosis of the upper gingiva: a case report.
AB  - INTRODUCTION: Localized amyloidosis in the head and neck is a rare and generally
      benign condition. In the oral cavity, amyloidosis usually involves the tongue or
      buccal mucosa. We present the second case of oral amyloidosis arising in the
      gingiva ever reported, to the best of our knowledge. CASE PRESENTATION: A 73-year
      old White Spanish man presented a persistent nodular mass involving his upper
      gingiva. The lesion was surgically resected and the histological examination
      revealed a subepithelial, multinodular amorphous and fibrillar accumulation.
      Staining of the specimen for Congo red proved positive, exhibiting a reddish
      colour under light microscopy and apple-green birefringence under polarized
      light. With immunohistochemical tests, pentagonal amyloid component was
      demonstrated. An extensive study excluded any systemic involvement; a diagnosis
      of localized primary amyloidosis was made. After 2 years of follow-up, no
      clinical progression to systemic amyloidosis or local recurrence was observed.
      CONCLUSIONS: Localized amyloidosis of the gingiva is an extremely rare condition
      that seems to show no clinically distinct feature. Histologic examination is the
      first step towards diagnosis, followed by immunohistochemical tests. The
      diagnosis of localized amyloidosis should always be integrated with blood tests,
      a bone marrow biopsy, echocardiography and digestive endoscopy to intercept
      systemic involvement.

PMID- 24939448
TI  - Macronutrient cycles: themed issue.

PMID- 24939449
TI  - Insights into in vitro binding of parecoxib to human serum albumin by
      spectroscopic methods.
AB  - Herein, we report the effect of parecoxib on the structure and function of human
      serum albumin (HSA) by using fluorescence, circular dichroism (CD), Fourier
      transforms infrared (FTIR), three-dimensional (3D) fluorescence spectroscopy, and
      molecular docking techniques. The Stern-Volmer quenching constants K(SV) and the
      corresponding thermodynamic parameters DeltaH, DeltaG, and DeltaS have been
      estimated by the fluorescence quenching method. The results indicated that
      parecoxib binds spontaneously with HSA through van der Waals forces and hydrogen
      bonds with binding constant of 3.45 * 10(4) M(-1) at 298 K. It can be seen from
      far-UV CD spectra that the alpha-helical network of HSA is disrupted and its
      content decreases from 60.5% to 49.6% at drug:protein = 10:1. Protein tertiary
      structural alterations induced by parecoxib were also confirmed by FTIR and 3D
      fluorescence spectroscopy. The molecular docking study indicated that parecoxib
      is embedded into the hydrophobic pocket of HSA.

PMID- 24939447
TI  - ARRY-334543 reverses multidrug resistance by antagonizing the activity of ATP
      binding cassette subfamily G member 2.
AB  - ARRY-334543 is a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases. We
      conducted this study to determine whether ARRY-334543 can enhance the efficacy of
      conventional anticancer drugs through interaction with ABC transporters. Lung
      cancer cell line NCI-H460 and its ABCG2-overexpressing NCI-H460/MX20, as well as
      the ABCG2-, ABCB1-, and ABCC10-overexpressing transfected cell lines were used
      for the reversal study. Our results demonstrated that ARRY-334543 (1.0 MUM)
      significantly reversed ABCG2-mediated multidrug resistance (MDR) by directly
      inhibiting the drug efflux function of ABCG2, resulting in the elevated
      intracellular accumulation of chemotherapeutic drugs in the ABCG2-overexpressing
      cell lines. In addition, in isolated membranes, ARRY-334543 stimulated ATPase
      activity and inhibited photolabeling of ABCG2 with [(125)I]-iodoarylazidoprazosin
      in a concentration-dependent manner indicating that this drug directly interacts
      at the drug-binding pocket of this transporter. ARRY-334543 (1.0 MUM) only
      slightly reversed ABCB1- and partially reversed ABCC10-mediated MDR suggesting
      that it exhibits high affinity toward ABCG2. Moreover, homology modeling
      predicted the binding conformation of ARRY-334543 at Arg482 centroid-based grid
      of ABCG2. However, ARRY-334543 at reversal concentrations did not affect the
      expression level of ABCG2, AKT and ERK1/2 and regulate the re-localization of
      ABCG2. We conclude that ARRY-334543 significantly reverses drug resistance
      mediated by ABCG2.

PMID- 24939450
TI  - Distribution of the internal branch of the human accessory nerve.
AB  - It was recently reported that the internal branch of the accessory nerve not only
      comprises the cranial root but also various combinations of the cranial root,
      spinal root, and the vagal component of the vagus nerve. The aim of this study
      was to demonstrate the anatomical distribution of each component of the internal
      branch of the human accessory nerve. Ten half-heads and necks of adult cadavers
      were used. The internal branch of the accessory nerve had three courses: the
      pharyngeal branch, the descending branch to the thorax, and the recurrent
      laryngeal nerve. The pharyngeal branch of the internal branch originated mainly
      from the vagus nerve, rather than from the cranial root of the accessory nerve.
      All of the components of the internal branch descended to the thorax along the
      vagus nerve. The recurrent laryngeal nerve comprised the internal branch and the
      vagus nerve in all specimens, and it was separated into bundles originating from
      the internal branch and vagus nerve. Both bundles gave off branches to the
      trachea and esophagus. The laryngeal distribution of the internal branch and
      vagus nerve was confirmed in the posterior cricoarytenoid, lateral
      cricoarytenoid, and thyroarytenoid muscles. These three laryngeal muscles were
      innervated by the cranial root and/or vagus nerve, but the distribution pattern
      was different in each specimen. Although the vagus nerve and cranial root are
      morphologically distinct nerves in the cranial cavity, they can be regarded
      functionally as the same nerve based on their distribution in the laryngeal
      muscles. 

PMID- 24939452
TI  - A surgical presentation for haemophilia A.
AB  - We present the case of a 5-year-old boy with no personal or family history of
      bleeding disorders, who suffered from recurrent post-tonsillectomy bleeds. The
      patient required multiple separate emergency visits to theatre in the 2-week
      postoperative period to achieve haemostasis. Initial baseline coagulation tests
      were found to be normal. However more extensive clotting studies revealed that
      the patient had an undiagnosed 'mild' haemophilia A. 

PMID- 24939451
TI  - Whole-lung irradiation in the treatment of metastatic synovial sarcoma.
AB  - Whole-lung irradiation (WLI) is standard of care in the treatment of patients
      with rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor and pulmonary metastases.
      However, it is not routinely utilized in the treatment of pulmonary metastases
      arising from other soft tissue sarcoma histologies. A patient presented with
      synovial sarcoma of his groin and punctate pulmonary metastases. After completion
      of multimodality treatment to his primary lesion, he received WLI. The patient is
      without evidence of disease at 3.8 years. This case demonstrates the need for
      further study of WLI in synovial sarcoma as it may improve outcomes in patients
      with this disease.

PMID- 24939454
TI  - Focal and abnormally persistent paralysis associated with congenital
      paramyotonia.
AB  - Mutations of the skeletal muscle voltage-gated sodium channel (NaV1.4) are an
      established cause of several clinically distinct forms of periodic paralysis and
      myotonia. Focal paresis has sometimes already been described. We report a case
      with atypical clinical manifestation comprising paramyotonia and cold-induced
      persistent and focal paralysis. A 27-year-old woman presented with paramyotonia
      congenita since her childhood. She experienced during her childhood one brief
      episode of generalised weakness. At the age of 27, she experienced a focal
      paresis lasting for several months. The known mutation p.Val1293Ile was found in
      the muscle sodium channel gene (SCN4A). Channel inactivation is involved in most
      Na(+) channelopathies. Fast inactivation is known to be responsible for the
      myotonia phenotype. We hypothesise that the V1293I mutation may also alter the
      slow inactivation in specific conditions, for example, prolonged cold exposure or
      prolonged and intensive exercise. This observation broadens the spectrum of
      clinical manifestations of this sodium channel mutation. 

PMID- 24939453
TI  - Clinical management of advanced schistosomiasis: a case of portal vein thrombosis
      induced splenomegaly requiring surgery.
AB  - We report for the first time in the Philippines a case of portal vein thrombosis
      in a 12 year old Filipino boy with advanced schistosomiasis. The boy was referred
      to the Research Institute for Tropical Medicine (RITM), Manila, due to a rapidly
      enlarging spleen post-praziquantel treatment. At RITM, liver function tests were
      within normal limits but complete blood examinations showed pancytopenia and
      abnormal coagulation times. Serum markers for hepatitis A, B and C were negative.
      Abdominal MRI revealed schistosome-induced periportal fibrosis. The main portal
      vein appeared thrombosed with characteristic cavernous transformation of the
      right portal vein. Varices were seen in the oesophagus, gastrohepatic ligament,
      and splenic hilum. The spleen was markedly enlarged, with parenchymal foci
      representing Gamna-Gandy bodies. The patient underwent splenectomy.
      Histopathologic findings in the liver showed moderate pipestem fibrosis and
      schistosome egg granulomas. The patient was discharged from the hospital in
      excellent clinical condition. 

PMID- 24939455
TI  - Radical surgical resection for giant primary mediastinal endodermal sinus tumour
      with pulmonary metastasis after chemotherapy: can be curative.
AB  - Primary non-seminomatous germ cell tumours of anterior mediastinum are uncommon.
      Endodermal sinus tumour of the anterior mediastinum (yolk sac) is a rare but
      lethal neoplasm. We present a case of an 18-year-old man who presented with chest
      pain, cough and haemosputum with markedly raised serum alpha-fetoprotein (AFP)
      levels above 112,000 ng/mL. Chest roentgenogram and CT showed a giant anterior
      mediastinal mass. CT guided biopsy revealed a diagnosis of endodermal sinus
      tumour. After the completion of chemotherapy, extensive surgical resection was
      carried out along with the right lung metastastectomy. Five years postresection
      follow-up the patient is disease free with normal serum tumour markers. This is
      the longest survival ever reported of such tumours with highest AFP level
      (>112,000 ng/mL) and lung metastasis.

PMID- 24939456
TI  - A carpenter's hypothenar hammer syndrome.

PMID- 24939458
TI  - Cancer and the Affordable Care Act: despite some challenges, most cancer experts
      say the new law benefits patients and survivors.

PMID- 24939457
TI  - In reference to redefining successful therapy in obstructive sleep apnea: a call
      to arms.

PMID- 24939459
TI  - Girls who eat peanut butter may improve their breast health.

PMID- 24939460
TI  - Long-term survival high for patients with low-grade gliomas.

PMID- 24939463
TI  - Molybdenum substitution for improving the charge compensation and activity of
      Li2MnO3.
AB  - Lithium-rich layer-structured oxides xLi2 MnO3 ? (1-x)LiMO2 (0<x<1, M=Mn, Ni, Co,
      etc.) are interesting and potential cathode materials for high energy-density
      lithium ion batteries. However, the characteristic charge compensation
      contributed by O(2-) in Li2 MnO3 leads to the evolution of oxygen during the
      initial Li(+) ion extraction at high voltage and voltage fading in subsequent
      cycling, resulting in a safety hazard and poor cycling performance of the
      battery. Molybdenum substitution was performed in this work to provide another
      electron donor and to enhance the electrochemical activity of Li2 MnO3 -based
      cathode materials. X-ray diffraction and adsorption studies indicated that Mo(5+)
      substitution expands the unit cell in the crystal lattice and weakens the Li?O
      and Mn?O bonds, as well as enhancing the activity of Li2 MnO3 by lowering its
      delithiation potential and suppressing the release of oxygen. In addition, the
      chemical environment of O(2-) ions in molybdenum-substituted Li2 MnO3 is more
      reversible than in the unsubstituted sample during cycling. Therefore molybdenum
      substitution is expected to improve the performances of the Li2 MnO3 -based
      lithium-rich cathode materials. 

PMID- 24939461
TI  - Biosynthesis of a water-soluble lipid I analogue and a convenient assay for
      translocase I.
AB  - Translocase I (MraY/MurX) is an essential enzyme in growth of the vast majority
      of bacteria that catalyzes the transformation from UDP-MurNAc-pentapeptide
      (Park's nucleotide) to prenyl-MurNAc-pentapeptide (lipid I), the first membrane
      anchored peptidoglycan precursor. MurX has received considerable attention in the
      development of new tuberculosis (TB) drugs due to the fact that the MurX
      inhibitors kill exponentially growing Mycobacterium tuberculosis (Mtb) much
      faster than clinically used TB drugs. Lipid I isolated from Mtb contains the C50
      prenyl unit that shows very poor water solubility; thus, this chemical
      characteristic of lipid I renders MurX enzyme assays impractical for screening
      and lacks reproducibility of the enzyme assays. We have established a scalable
      chemical synthesis of Park's nucleotide-N(epsilon)-dansylthiourea 2 that can be
      used as a MurX enzymatic substrate to form lipid I analogues. In our
      investigation of the minimum structure requirement of the prenyl phosphate in the
      MraY/MurX-catalyzed lipid I analogue synthesis with 2, we found that neryl
      phosphate (C10 phosphate) can be recognized by MraY/MurX to generate the water
      soluble lipid I analogue in quantitative yield under the optimized conditions.
      Here, we report a rapid and robust analytical method for quantifying MraY/MurX
      inhibitory activity of library molecules. 

PMID- 24939462
TI  - Ultra-sensitive biosensor for K-ras gene detection using enzyme capped gold
      nanoparticles conjugates for signal amplification.
AB  - In this study, an ultra-sensitive hairpin DNA-based electrochemical DNA biosensor
      for K-ras gene detection is described. Gold nanoparticles (Au-NPs) and
      horseradish peroxidase (HRP)-streptavidin capped Au-NPs (HAS) conjugates are used
      for signal amplification. Initially, hairpin DNA dually labeled with thiol at its
      5' end and with biotin at its 3' end is immobilized on the surface of Au-NPs
      modified electrode, and the hairpin DNA is in a "closed" state; hence, the HAS
      conjugates are shielded from being approached by the biotin due to steric
      hindrance. However, in the presence of target DNA, the target DNA hybridizes with
      the loop structure of hairpin DNA and causes conformational change, resulting in
      biotin forced away from the electrode surface, thereby becoming accessible for
      the HAS conjugates. Thus, the HAS conjugates are linked to the electrode surface
      via the specific interaction between biotin and streptavidin. Electrochemical
      detection was performed in phosphate-buffered saline (PBS) containing
      tetramethylbenzidine (TMB) and H2O2. Under optimal conditions, the peak current
      differences (DeltaI) are linear with the target DNA in the range from 0.1 fM to 1
      nM with a detection limit of 0.035 fM. Furthermore, this biosensor also
      demonstrates its excellent specificity for single-base mismatched DNA.

PMID- 24939464
TI  - Computational study of graphene growth on copper by first-principles and kinetic
      Monte Carlo calculations.
AB  - In this work the growth of a graphene monolayer on copper substrate, as typically
      achieved via chemical vapor deposition of propene (C3H6), was investigated by
      first-principles and kinetic Monte Carlo calculations. A comparison between
      calculated C1s core-level binding energies and electron spectroscopy measurements
      showed that graphene nucleates from isolated carbon atoms adsorbed on surface
      defects or sub-superficial layers upon hydrocarbon fragmentation. In this
      respect, ab initio nudged elastic band simulations yield the energetic barriers
      characterizing the diffusion of elemental carbon on the Cu(111) surface and
      atomic carbon uptake by the growing graphene film. Our calculations highlight a
      strong interaction between the growing film edges and the copper substrate,
      indicative of the importance of the grain boundaries in the epitaxy process.
      Furthermore, we used activation energies to compute the reaction rates for the
      different mechanisms occurring at the carbon-copper interface via harmonic
      transition state theory. Finally, we simulated the long-time system growth
      evolution through a kinetic Monte Carlo approach for different temperatures and
      coverage. Our ab initio and Monte Carlo simulations of the out-of-equilibrium
      system point towards a growth model strikingly different from that of standard
      film growth. Graphene growth on copper turns out to be a catalytic, thermally
      activated process that nucleates from carbon monomers, proceeds by adsorption of
      carbon atoms, and is not self-limiting. Furthermore, graphene growth seems to be
      more effective at carbon supersaturation of the surface-a clear fingerprint of a
      large activation barrier for C attachment. Our growth model and computational
      results are in good agreement with recent X-ray photoelectron spectroscopy
      experimental measurements. 

PMID- 24939465
TI  - Alternative analytical forms to model diatomic systems based on the deformed
      exponential function.
AB  - Using a deformed exponential function and the molecular-orbital theory for the
      simplest molecular ion, two new analytical functions are proposed to represent
      the potential energy of ground-state diatomic systems. The quality of these new
      forms was tested by fitting the ab initio electronic energies of the system LiH,
      LiNa, NaH, RbH, KH, H2, Li2, K2, H 2 (+) , BeH(+) and Li 2 (+) . From these fits,
      it was verified that these new proposals are able to adequately describe
      homonuclear, heteronuclear and cationic diatomic systems with good accuracy.
      Vibrational spectroscopic constant results obtained from these two proposals are
      in good agreement with experimental data. 

PMID- 24939466
TI  - Rovibrational energy and spectroscopic constant calculations of CH4?CH4, CH4?H2O,
      CH4?CHF3, and H2O?CHF3 dimers.
AB  - In this work, we performed a thorough investigation of potential energy curves,
      rovibrational spectra, and spectroscopic constants for dimers whose interactions
      are mediated by hydrogen bonds and other hydrogen interactions. Particularly, we
      deal with CH4?CH4, CH4?H2O, CH4?CHF3, and H2O?CHF 3 dimers by employing accurate
      electronic energy calculations with two different basis sets at the MP2 level of
      theory. Following this, the discrete variable representation method was applied
      to solve the nuclear Schrodinger equation, thus obtaining spectroscopic constants
      and rovibrational spectra. The harmonic constant, omega e , presents a direct
      relation to the strength of dimer interactions. As a general rule, it was found
      that a decrease of interatomic distances is followed by the increase of D e for
      all dimers. This behavior suggests that the interaction of CH4?CH4 is the weakest
      among all dimers, followed by CH4?CHF3, CH4?H2O and the strongest interaction
      given by the H2O?CHF 3 dimer.

PMID- 24939467
TI  - Comparative optical coherence tomography study of differences in scleral shape
      between the superonasal and superotemporal quadrants.
AB  - PURPOSE: To determine the differences in scleral shape between the superonasal
      and superotemporal quadrants, the sites of scleral flap creation in
      trabeculectomy, using anterior segment optical coherence tomography (OCT).
      METHODS: Thirty-four right eyes of 34 enrolled subjects without ocular disease,
      with the exception of cataract or ametropia, were studied. Mean patient age was
      63.2 +/- 15.9 (standard deviation) years (range 28-84 years). The same examiner
      captured all images using anterior segment swept source OCT. The mean
      measurements were calculated from three images captured for each eye, 60 degrees 
      from the horizontal line passing through the pupillary center in the superonasal
      and superotemporal sclera. The radius of the scleral surface curvature and the
      area of the convex part of the sclera between the superonasal and the
      superotemporal quadrants were determined using image analysis software and the
      paired t test. RESULTS: The radius of the scleral curvature was significantly
      different in the superonasal quadrant and superotemporal quadrant (34.3 +/- 12.6
      vs. 18.3 +/- 3.6 mm, respectively; P < 0.001). The area of the convex part of the
      sclera was also significantly different in the superonasal and superotemporal
      quadrants (0.36 +/- 0.1 vs. 0.57 +/- 0.1 mm(2), respectively; P < 0.001).
      CONCLUSIONS: Anterior segment OCT analysis of the scleral shape revealed a more
      gradual scleral gradient in the superonasal quadrant compared with the
      superotemporal quadrant.

PMID- 24939469
TI  - The PREDICT (increasing the participation of the elderly in clinical trials)
      study: the charter and beyond.
AB  - There is general agreement that the growth of the numbers of older people
      throughout the world has significant implications for both health and social care
      and for the prevention and treatment of disease and disability. The optimum use
      of pharmaceuticals and possibly nutraceuticals is, and will to a greater extent,
      therefore be of crucial importance. A snapshot of the current status of older
      people in relation to the issues discussed in this review is provided in an
      informative report published by Age UK.

PMID- 24939470
TI  - Advanced stage pancreatic cancer: novel therapeutic options.
AB  - Despite advances in our understanding of the molecular and genetic basis of
      pancreatic cancer, it continues to be a therapeutic challenge. Gemcitabine
      approved by FDA in 1997, offers modest improvement of tumor-related symptoms and
      marginal advantage of survival. Many chemotherapeutic agents have been compared
      against or combined with gemcitabine in randomized Phase III trials and no drug
      was shown to be superior to single-agent gemcitabine except FOLFIRINOX and nab
      paclitaxel plus gemcitabine. On the other hand, efforts to integrate targeted
      agents such as BAY 12-9566, SCH 66336, bevacizumab, cetuximab, axitinib and
      sorafenib have been quite dismal despite extensive pre-clinical and clinical
      research over the last decade in the field of novel agents. To date, erlotinib
      remains the only biological agent that has demonstrated a small, but significant,
      added benefit to single agent gemcitabine. However, numerous new agents,
      including monoclonal antibodies and tyrosine kinase inhibitors, are currently
      being tested in an attempt to achieve better response, while maintaining a safe
      toxicity profile. In this article, the author discusses the management of
      advanced pancreatic and the current role of novel agents in this setting.

PMID- 24939468
TI  - Investigating population history using temporal genetic differentiation.
AB  - The rapid advance of sequencing technology, coupled with improvements in
      molecular methods for obtaining genetic data from ancient sources, holds the
      promise of producing a wealth of genomic data from time-separated individuals.
      However, the population-genetic properties of time-structured samples have not
      been extensively explored. Here, we consider the implications of temporal
      sampling for analyses of genetic differentiation and use a temporal coalescent
      framework to show that complex historical events such as size reductions,
      population replacements, and transient genetic barriers between populations leave
      a footprint of genetic differentiation that can be traced through history using
      temporal samples. Our results emphasize explicit consideration of the temporal
      structure when making inferences and indicate that genomic data from ancient
      individuals will greatly increase our ability to reconstruct population history. 

PMID- 24939471
TI  - Antiviral therapy for chronic hepatitis C in 2014.
AB  - An all-oral therapy for treating hepatitis C (HCV) is now available for the most
      common genotypes although interferon-based therapy is still recommended for
      interferon-eligible patients with HCV genotype 1. For most patients, a prior
      history of treatment or presence of cirrhosis does not appear to significantly
      impact eradication rates with direct acting antivirals (DAA). The promising
      results from the numerous clinical trials of DAA's for HCV together with their
      tolerability represent a tremendous advance in our management of this disease,
      particularly as treatment is often well-tolerated, associated with few side
      effects and significantly shortened in duration. We will review several of the
      peer-reviewed landmark studies of DAA's for the treatment HCV and conclude with
      an expert commentary and five year view.

PMID- 24939472
TI  - Diagnostic algorithm for syncope.
AB  - Syncope is a common symptom with many causes. Affecting a large proportion of the
      population, both young and old, it represents a significant healthcare burden.
      The diagnostic approach to syncope should be focused on the initial evaluation,
      which includes a detailed clinical history, physical examination and 12-lead
      electrocardiogram. Following the initial evaluation, patients should be risk
      stratified into high or low-risk groups in order to guide further investigations
      and management. Patients with high-risk features should be investigated further
      to exclude significant structural heart disease or arrhythmia. The ideal
      currently-available investigation should allow ECG recording during a spontaneous
      episode of syncope, and when this is not possible, an implantable loop recorder
      may be considered. In the emergency room setting, acute causes of syncope must
      also be considered including severe cardiovascular compromise due to pulmonary,
      cardiac or vascular pathology. While not all patients will receive a conclusive
      diagnosis, risk-stratification in patients to guide appropriate investigations in
      the context of a diagnostic algorithm should allow a benign prognosis to be
      maintained. 

PMID- 24939473
TI  - UK veterinarians' experiences with euthanasia.

PMID- 24939474
TI  - Investigation of parallel and simultaneous selection for collie eye anomaly and
      ivermectin toxicosis.

PMID- 24939475
TI  - Gender, masculinity and migration: Mexican men and reproductive health in the
      Californian context.
AB  - An appreciation of the social, cultural and economic dimensions of gender and
      sexuality is important in increasing reproductive health service utilisation.
      This analysis of recent Mexican male immigrants in Southern California focuses on
      changing views of gender roles, masculinity and relationship dynamics in the
      context of migration in order to explain low levels of reproductive healthcare
      utilisation. Semi-structured, in-depth interviews were conducted with 23 men who
      had migrated from Mexico. Some men saw their migratory experience as empowering,
      both individually and within the couple context. Migration reinforced positive
      male qualities, such as being a good provider. However, for others, the levelling
      of economic power between immigrant couples challenged traditional male gender
      roles and threatened men's identities. Maintaining control and decision-making
      power, especially in reproduction, remained tenacious, especially among older
      men. In response to immigration, however, men's views of ideal family size and
      contraceptive method preferences had evolved. The migration process caused some
      divisions in family networks and aspirations of fatherhood as an expression of
      masculinity contributed to varying levels of contraceptive use. Recommendations
      are made on factors that may empower male clients more actively to seek
      reproductive healthcare in the context of more equitable couple decision-making. 

PMID- 24939476
TI  - Left ventricular rupture after myocardial infarction.

PMID- 24939477
TI  - Comparable benefit of beta-blocker therapy in heart failure across regions of the
      world: meta-analysis of randomized clinical trials.
AB  - BACKGROUND: There is a concern about geographical region heterogeneity regarding
      clinical benefit of beta-blocker (BB) therapy in heart failure with reduced
      ejection fraction (HFrEF). This study sought to compare benefits of BB use within
      randomized controlled trials (RCTs) that enrolled patients with HFrEF from North
      America (NA) compared with other regions of the world (ROW). METHODS: We
      conducted a meta-analysis using MEDLINE, EMBASE, Cochrane Library, Web of
      Science, and Scopus (inceptions-December 2012) of BB RCTs stratified according to
      NA vs ROW. The primary end point was all-cause mortality and secondary end points
      were cardiovascular death, sudden death, death due to pump failure, and premature
      drug discontinuation. Summary odds ratios (ORs) and 95% confidence intervals
      (CIs) for each outcome were calculated with interaction terms for region. Two
      sided P values were calculated with P < 0.05 considered significant. RESULTS: The
      analysis included 16 RCTs with 14,452 patients; 7 trials were conducted in NA and
      9 trials in ROW with follow-up durations of 3-58 months. All-cause mortality was
      consistently reduced in NA (OR, 0.82; 95% CI, 0.71-0.96; P = 0.01) and ROW (OR,
      0.76; 95% CI, 0.69-0.84; P < 0.001; P-interaction = 0.40). Overall and according
      to region, all secondary end points including premature drug discontinuation were
      also less with BB therapy (P-interactions all >= 0.10). CONCLUSIONS: For the
      regions represented in the included trials, there is no evidence to suggest that
      geographic region is a significant moderator of clinical outcomes with BB therapy
      in HFrEF patients.

PMID- 24939479
TI  - Unanticipated bleeding with the etonogestrel implant: advice and therapeutic
      interventions.

PMID- 24939480
TI  - Should we vaccinate against and test for human papillomavirus infection in
      adolescent girls and women with a neovagina?

PMID- 24939482
TI  - Communication.

PMID- 24939481
TI  - Jaydess(r) levonorgestrel intrauterine system.

PMID- 24939483
TI  - Doctors for a Woman's Choice on Abortion.

PMID- 24939485
TI  - Comment on 'Continuing need for and provision of a service for non-standard
      implant removal'.

PMID- 24939486
TI  - Comment on 'Continuing need for and provision of a service for non-standard
      implant removal': authors' response.

PMID- 24939487
TI  - Incomplete IUS removal.

PMID- 24939488
TI  - Comment on 'Practical advice for avoidance of pain associated with insertion of
      intrauterine contraceptives': authors' response.

PMID- 24939489
TI  - Sevoflurane in combination with remifentanil for tracheal extubation after
      otologic surgery.
AB  - PURPOSE: The effects of i.v. remifentanil in combination with an inhaled
      anesthetic to facilitate tracheal extubation of deeply anesthetized adults after
      otologic surgery are investigated. METHODS: Fifty patients undergoing middleear
      surgery were recruited for the study. All patients were administered deep
      anesthesia (i.v. fentanil, propofol, and mivacurium) and intubated, with
      subsequent administration of inhaled sevoflurane for anesthesia maintenance.
      Prior to endotracheal tube removal, the patients received i.v. dexamethasone,
      ondansetron hydrochloride, and parecoxib and were randomly allocated to two
      groups. In group S (n = 25), anesthesia was maintained with sevoflurane alone
      (1.3 times the minimum effective alveolar concentration [MAC]), while patients in
      group SR (n = 25) received low-dose i.v. remifentanil and a reduced dose of
      sevoflurane (1.0 MAC). RESULTS: The mean remifentanil dosage was 0.028 MUg/kg per
      minute. Relative to patients in group S, patients in group SR had a significantly
      lower mean respiratory rate (6.4 breaths per minute versus 15.8 breaths per
      minute, p < 0.01) and end-tidal carbon dioxide pressure (48.1 mm Hg versus 52.1
      mm Hg, p < 0.05) after extubation. Postextubation airway obstructions requiring
      nasal airway placement were less frequent in group SR (14 cases versus 2 cases in
      group S, p < 0.05); patients in group SR also had a shorter mean time to
      awakening (19.5 minutes versus 15.8 minutes, p < 0.05) and a shorter mean time to
      orientation (31.4 minutes versus 26.1 minutes, p < 0.05). CONCLUSION: Sevoflurane
      combined with remifentanil provided rapid recovery and appeared to be safe for
      deep-anesthesia tracheal extubation in adult patients after otologic surgery.

PMID- 24939490
TI  - Dalbavancin approved for acute skin infections.

PMID- 24939491
TI  - Standardize units for dosing liquid oral prescription medicines, task group says.

PMID- 24939492
TI  - Hospital engagement networks report successes in decreasing adverse drug events.

PMID- 24939493
TI  - Pharmacist fits on high-intensity transitional care team.

PMID- 24939495
TI  - Need for pharmacist awareness of Chagas disease.

PMID- 24939496
TI  - Managing multiple residents with incongruent personalities: a case-based scenario
      for the new preceptor.

PMID- 24939497
TI  - Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome.
AB  - PURPOSE: The pharmacology, pharmaco-kinetics, and clinical efficacy and safety of
      linaclotide in the management of chronic constipation (CC) and constipation
      predominant irritable bowel syndrome (IBS-C) are reviewed. SUMMARY: Linaclotide
      (Linzess, Forest Pharmaceuticals) is a 14-amino acid peptide indicated for the
      treatment of adults with CC and IBS-C. Linaclotide acts on guanylate cyclase-C
      receptors on the luminal membrane to increase chloride and bicarbonate secretions
      into the intestine and inhibit the absorption of sodium ions, thus increasing the
      secretion of water into the lumen and improving defecation; the drug is minimally
      absorbed into the systemic circulation. Linaclotide is approved by the Food and
      Drug Administration (FDA) for oral once-daily administration at doses of 145 MUg
      for CC and 290 MUg for IBS-C. In placebo-controlled Phase III clinical trials,
      linaclotide significantly increased weekly spontaneous bowel movements and
      complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in
      patients with CC. In patients with IBS-C, linaclotide was demonstrated to be
      effective in meeting FDA-recommended endpoints such as reductions of at least 30%
      from baseline in abdominal pain scores and CSBM frequency. The most common
      adverse effect of linaclotide is diarrhea, which was reported in 16-20% of
      clinical trial participants. CONCLUSION: Linaclotide is an important advance in
      the treatment of CC and IBS-C, with a novel mechanism of action resulting in
      accelerated intestinal transit. In clinical trials, linaclotide demonstrated
      efficacy relative to placebo for treatment of both CC and IBS-C. Linaclotide's
      adverse effects are generally mild and confined to the gastrointestinal tract.

PMID- 24939498
TI  - Common questions regarding clinical use of axitinib in advanced renal cell
      carcinoma.
AB  - PURPOSE: An overview of the responses to some of the most frequently asked
      questions regarding axitinib administration and dosage modifications used in
      clinical practice are presented. SUMMARY: Axitinib was approved for second-line
      treatment of advanced renal cell carcinoma by the Food and Drug Administration on
      January 27, 2012. Inquiries received over the first six months after the approval
      date were reviewed. A large number of questions were related to administration of
      axitinib in different patient populations or in patients with various
      comorbidities, such as its (1) use in patients unable to swallow oral medication
      or administration of axitinib via a nasogastric tube, (2) use in patients with
      renal or hepatic impairment, (3) central nervous system penetration and use in
      patients with brain metastases, (4) drug interactions, particularly with
      anticoagulants, and (5) dosage modifications. Responses to these inquiries were
      provided based on the published literature or from data on file from the
      manufacturer. The dosage of axitinib can be adjusted for use in patients with
      hepatic impairment or in patients who cannot otherwise tolerate the usual
      regimen. Patients taking concomitant warfarin can also take axitinib, and
      patients who cannot swallow oral medications can receive a liquid formulation of
      the drug, though its efficacy and comparability to the tablet formulation has not
      been tested. CONCLUSION: Based on the published literature and company data on
      file, the axitinib dosage may be modified to accommodate patients with renal or
      hepatic impairment, who cannot swallow oral medication, are receiving concomitant
      warfarin, or who cannot otherwise tolerate the standard dosage regimen. For
      patients who cannot swallow, an oral suspension can be prepared because crushing
      axitinib is not recommended.

PMID- 24939499
TI  - Resolution of clopidogrel-associated polyarthritis after conversion to prasugrel.
AB  - PURPOSE: A case of acute polyarthritis associated with the use of clopidogrel is
      reported. SUMMARY: A 72-year-old retired Caucasian man arrived at the emergency
      department with confusion, a temperature of 101  degrees F, difficulty walking,
      leukocytosis, and diffuse joint aches. The patient reported decreased oral intake
      and progressive weakness. Upon questioning, he reported pain in almost all
      joints. The patient reported no rash, twitching, or focal numbness. Approximately
      two weeks earlier, the patient underwent a nonemergent percutaneous coronary
      intervention secondary to coronary artery disease, after which clopidogrel and
      aspirin were initiated. The patient had no complaints the week after his stent
      placement. Approximately four days before this hospital admission, the patient
      reported acute onset of lateral left leg pain. The symptoms progressed in the
      following days, necessitating admission to the hospital. The patient's symptoms
      markedly improved with discontinuation of clopidogrel and administration of
      corticosteroids. Prasugrel was initiated before hospital discharge. The patient
      reported no arthralgias and continued compliance with prasugrel during follow-up
      telephone calls by the clinical pharmacist at two and six weeks. Applying the
      Naranjo et al. probability scale to this case yielded a score of 5, suggesting
      that clopidogrel was the probable cause of the patient's adverse reaction.
      CONCLUSION: A patient developed acute polyarthritis evidently associated with
      clopidogrel therapy. Symptoms resolved after prasugrel was substituted for
      clopidogrel and reappeared after two doses of clopidogrel were taken
      inadvertently.

PMID- 24939500
TI  - Dosing strategy to allow continued therapy with daptomycin after asymptomatic
      increases in creatine kinase levels.
AB  - PURPOSE: A case series in which a novel dosing strategy for managing mild,
      asymptomatic creatine kinase (CK) increases associated with daptomycin therapy is
      presented. SUMMARY: Eight patients received a mean daptomycin dosage of 7.75
      mg/kg/day for a median duration of 42 days. Seven of the eight patients were
      being treated for a bone and joint infection, and all but one had methicillin
      resistant Staphylococcus aureus. All patients had asymptomatic increases in CK
      concentrations during daptomycin therapy (peak range, 400-1200 IU/L). A single
      daptomycin dose was withheld from each patient, and therapy was resumed 24 hours
      later, most often at the same dosage. The elevated CK values in these patients
      resolved, and all patients were able to complete daptomycin therapy without
      further increases in CK elevations. These findings indicate that withholding one
      dose of daptomycin during treatment may allow patients with asymptomatic,
      elevated CK concentrations to continue therapy with CK level normalization.
      Although the mechanism of daptomycin-mediated muscle injury is not fully
      understood, a reduction in daptomycin exposure via a one-dose cessation of
      therapy may allow for physiological restoration of sarcolemma membrane integrity
      that may be disrupted by daptomycin in individuals exhibiting CK elevation.
      CONCLUSION: A single daptomycin dose was withheld from eight patients with
      asymptomatic increases in serum CK concentrations, then daptomycin therapy was
      resumed 24 hours later, most often at the previous dosage. The CK concentrations
      returned to normal, and all patients were able to complete daptomycin therapy
      without further increases in CK concentrations.

PMID- 24939501
TI  - Design, implementation, and evaluation of a thrice-daily cartfill process.
AB  - PURPOSE: Efficiencies achieved through a redesign of the central pharmacy
      cartfill process at a large academic medical center are reported. SUMMARY: In an
      initiative to expand clinical pharmacy services in a budget-neutral manner,
      pharmacists at the University of Wisconsin Hospital and Clinics (UWHC) led the
      transition from a once-daily to a thrice-daily medication cartfill model designed
      to better align pharmacy operations with patterns of medication ordering,
      delivery, and order discontinuation. A pre-post analysis demonstrated several
      benefits of the shift to thrice-daily cartfill, including a 32.7% decrease in the
      mean daily number of extemporaneously prepared oral doses. Overall, the new
      cartfill process resulted in reduction in lead times for three of four peak
      delivery periods, roughly a 55-65% reduction. During the postimplementation
      period, the frequency of requests for missing medication doses through the
      electronic medical record (EMR) system increased from 1.13% to 1.43%; however,
      this increase may have been the result of improved nurse adherence to EMR
      protocols for requests for missing medications. CONCLUSION: Implementation of a
      thrice-daily cartfill process and ancillary changes at UWHC resulted in a 2.1%
      increase in cartfill doses dispensed, a 44.1% decrease in first doses dispensed,
      and a 42.9% decrease in the number of medications returned to the central
      pharmacy. This resulted in a reduction in waste within pharmacy operations and
      allowed for redeployment of two technician full-time equivalents to expand
      pharmacy services.

PMID- 24939502
TI  - Stability of hydroxyprogesterone caproate alone and in a compounded
      pharmaceutical product.
AB  - PURPOSE: The chemical stability of hydroxyprogesterone caproate in powder form
      and in a pharmaceutical formulation under different experimental conditions was
      evaluated. METHODS: Pure hydroxyprogesterone caproate was subjected to
      hydrolysis, photolysis, and thermal degradation. The content of
      hydroxyprogesterone caproate in pharmaceutical products was evaluated after using
      two different sterilization methods and after exposure to light.
      Hydroxyprogesterone caproate and its degradation products were analyzed using a
      validated reverse-phase high-performance liquid chromatographic method. Variables
      examined included specificity, accuracy, precision, linearity, theoretical plate
      numbers, signal:noise ratio, resolution between any two peaks, and relative
      standard deviation of the peak response. Statistical analysis was performed with
      Stata software, version 11 (StataCorp, College Station, TX). Mean values and
      standard deviations were calculated. The level of significance was set at p <
      0.05. RESULTS: Components of hydroxyprogesterone caproate and organic impurities
      in pharmaceutical products were scanned with wide ultraviolet wavelength from 200
      to 400 nm. In powder form, hydroxyprogesterone caproate was stable when exposed
      to high temperatures and light. Considerable degradation of hydroxyprogesterone
      caproate was observed in alkaline solution, with the major degradation product
      being hydroxyprogesterone. Much less degradation of hydroxyprogesterone caproate
      was observed in acidic conditions over 72 hours. The content of
      hydroxyprogesterone caproate in pharmaceutical products was not altered by the
      sterilization methods (filtration or heat sterilization) used and after exposure
      to light. CONCLUSION: Hydroxyprogesterone caproate in powder form and in a
      pharmaceutical formulation under different experimental conditions appeared to be
      fairly stable in the presence of strong acid, high temperatures, and light.

PMID- 24939503
TI  - Choosing to use the most powerful model in the world.

PMID- 24939504
TI  - Impact of an antimicrobial stewardship program on patients with acute bacterial
      skin and skin structure infections.
AB  - PURPOSE: The impact of an antimicrobial stewardship program (ASP) on the
      management of therapy and hospital resources for patients with acute bacterial
      skin and skin structure infections (ABSSSIs) at a community teaching hospital was
      evaluated. METHODS: A retrospective, observational chart review was performed to
      evaluate the impact of the ASP on patients admitted to Akron City Hospital with a
      diagnosis of ABSSSI between February 1 and August 20, 2012. Information on
      patient demographic characteristics, comorbidities, ABSSSI subtype, antibiotic
      therapy, microbiology, surgical interventions, and ASP recommendations was
      collected from medical records and the ASP intervention log. ASP recommendations
      were organized into five categories: dosage changes, de-escalation, antibiotic
      regimen change (i.e., change antibiotic regimen to a broad-spectrum antimicrobial
      or target a pathogen not being covered), infectious diseases (ID) formal
      consultation, and other. RESULTS: A total of 62 patients were included in the
      study. A total of 85 recommendations were made to attending physicians for these
      62 patients, with an acceptance rate of 95%. The most common interventions
      included dosage changes, de-escalation, antibiotic regimen change, and ID
      consultation. When compared with historical data for 1149 patients, the
      intervention group had a significantly lower mean length of stay (LOS). The 30
      day all-cause readmission rate was also significantly lower in the intervention
      group; however, the 30-day ABSSSI readmission rate did not differ significantly
      between groups. CONCLUSION: Interventions made by an ASP including a clinical
      pharmacist were associated with significant reductions in the mean LOS and 30-day
      all-cause readmission rate for patients with an ABSSSI compared with historical
      data.

PMID- 24939507
TI  - A description of the complete mitochondrial genomes of Amphiporus formidabilis,
      Prosadenoporus spectaculum and Nipponnemertes punctatula (Nemertea:
      Hoplonemertea: Monostilifera).
AB  - We sequenced the complete mitochondrial genomes (mitogenomes) of three
      Hoplonemertea species, Amphiporus formidabilis, Prosadenoporus spectaculum and
      Nipponnemertes punctatula, which are 14,616, 14,655 and 15,354 bp in length,
      respectively. Each of the three circular mitogenomes consists of 37 typical genes
      and some non-coding regions. The nucleotide composition of the coding strand is
      biased toward T, almost a half of total nucleotides in these mitogenomes. There
      are many poly-T tracts across these mitogenomes, which exhibit T-number variation
      within different clones of protein-coding genes, mainly resulting from false PCR
      amplification. The major non-coding regions have tandem repeat motifs and hairpin
      like structures that may be associated with the initiation of replication or
      transcription. Data published to date for nemerteans show that Palaeonemertea
      species usually bear the largest mitogenomes, while representatives in the more
      recently derived Distromatonemertea clade bear the smallest ones; and that the
      gene arrangement of mitogenomes seems to be variable within the phylum Nemertea,
      but stable within either of Heteronemertea and Hoplonemertea.

PMID- 24939509
TI  - Self-enhancement and the life script in future thinking across the lifespan.
AB  - Studies comparing memory and future event simulation find that future events are
      more positive, and more often depend on life script events (e.g., culturally
      normative landmark events) than past events. Previous research does not address
      the link between this positivity bias and the life stage of college-age
      participants or their reliance on these scripted events. To examine this
      positivity bias, narratives of past and anticipated future events were elicited
      from participants aged 18-74 years, and were examined for reliance on the life
      script and valence ratings. Results showed that, across age groups, future events
      were rated as more positive than past events, and that life script events were
      common in the distant future. Notably, whereas younger adult age groups wrote
      primarily about their own life script events, older participants more commonly
      wrote about attending the life script events of significant others, such as
      children and grandchildren. These findings suggest that simulated future events
      play a valuable role in self-enhancement across the lifespan. Furthermore, the
      life script can be viewed as a useful search mechanism when one is missing the
      episodic details that are more available in memories; however, it is not the
      source of positivity bias for future events. 

PMID- 24939508
TI  - Inertio-elastic focusing of bioparticles in microchannels at high throughput.
AB  - Controlled manipulation of particles from very large volumes of fluid at high
      throughput is critical for many biomedical, environmental and industrial
      applications. One promising approach is to use microfluidic technologies that
      rely on fluid inertia or elasticity to drive lateral migration of particles to
      stable equilibrium positions in a microchannel. Here, we report on a hydrodynamic
      approach that enables deterministic focusing of beads, mammalian cells and
      anisotropic hydrogel particles in a microchannel at extremely high flow rates. We
      show that on addition of micromolar concentrations of hyaluronic acid, the
      resulting fluid viscoelasticity can be used to control the focal position of
      particles at Reynolds numbers up to Re~10,000 with corresponding flow rates and
      particle velocities up to 50 ml min(-1) and 130 m s(-1). This study explores a
      previously unattained regime of inertio-elastic fluid flow and demonstrates
      bioparticle focusing at flow rates that are the highest yet achieved. 

PMID- 24939510
TI  - A national survey of admission practices for late preterm infants in England.
AB  - BACKGROUND: Infants born at 34(+0) to 36(+6) weeks gestation are defined as 'late
      preterm' infants. It is not clear whether these babies can be managed on the
      postnatal ward (PNW) or routinely need to be admitted to the neonatal unit after
      birth. AIM: To conduct a national survey of admission practice for late preterm
      and low birth weight infants directly to the PNW after birth in England. METHODS:
      All neonatal units were identified from the Standardised Electronic Neonatal
      Database (SEND). Individual units were contacted and data collected on their
      admission practice. RESULTS: All 180 neonatal units in England responded. 49, 84
      and 47 Units were Special Care Units (SCUs), Local Neonatal Units (LNUs) and
      Neonatal Intensive Care Units (NICUs) respectively. 161 units (89%) had written
      guidelines in relation to direct PNW admission for late preterm infants.The mean
      gestational age of infants admitted directly to the PNW was significantly lower
      in LNUs compared to SCUs and NICUs compared to LNUs. Mean birth weight limit for
      direct PNW admission was significantly lower in NICUs compared to SCUs.72 units
      had PNW nursery nurses. There was no significant difference in gestational age or
      birth weight limit for direct PNW admission in the presence of PNW nursery
      nurses. CONCLUSIONS: Admission practices of late preterm infants directly to the
      PNW varies according to designation of neonatal unit in England. Further studies
      are needed to establish the factors influencing these differences.

PMID- 24939512
TI  - Intravitreal therapy in bilateral neovascular age-related macular degeneration.

PMID- 24939513
TI  - Long-term reproducibility of diurnal intraocular pressure patterns in patients
      with glaucoma.
AB  - PURPOSE: To evaluate the long-term reproducibility of diurnal intraocular
      pressure (IOP) patterns in patients with primary open-angle glaucoma (POAG).
      DESIGN: Database study. PARTICIPANTS: Ninety-two patients with POAG. METHODS: We
      reviewed the records of patients with POAG who underwent 4 diurnal IOP curve
      measurements 6 months apart with Goldmann applanation tonometry recorded in the
      sitting position at 9 am, 10 am, 11 am, noon, 2 pm, 3 pm, 4 pm, and 5 pm. MAIN
      OUTCOME MEASURES: Intervisit agreement of IOP by time point and of diurnal IOP
      curve parameters (mean, standard deviation, range, maximum, maximum hour,
      minimum, and minimum hour) was assessed using intraclass correlation coefficients
      (ICCs). Analyses were performed in all eyes and separately in eyes with and
      without hypotensive medications, and in eyes naive and non-naive of filtering
      surgery. RESULTS: Between-visit agreement of IOP values at each time point was
      generally poor, with ICCs ranging from 0.26 to 0.77 in all patients (1 of 8 time
      points with ICC >0.75), from -0.07 to 0.60 in patients without hypotensive
      medications (zero time points with ICC >0.75), from 0.29 to 0.80 in patients with
      hypotensive medications (3 time points with ICCs >0.75), from 0.21 to 0.68 in
      filtering surgery-naive patients (zero time points with ICC >0.75), and from 0.21
      to 0.87 in patients with previous filtering surgeries (5 time points with ICCs
      >0.75). The predictive value of the first diurnal IOP curve to estimate the risk
      of IOP fluctuations during the 3 subsequent curves was limited (only 6.4% of the
      patients with an IOP range >=30% of the mean IOP on the first curve presented
      similar fluctuations on the 3 subsequent curves; 77.1% of the patients who did
      not have an IOP range >=30% of the mean IOP on the first curve had an IOP range
      >=30% of the mean IOP on at least 1 of the 3 subsequent curves). CONCLUSIONS:
      Patients with POAG do not manifest a reproducible diurnal IOP pattern from month
      to month. A single diurnal IOP curve in patients with POAG poorly characterizes
      IOP fluctuations and has limited value in clinical practice.

PMID- 24939514
TI  - Evaluation of the effectiveness of improved hydrogen peroxide in the operating
      room.
AB  - The aim of our study was to evaluate the effectiveness of a 1-step, ready-to-use
      improved hydrogen peroxide (IHP) cleaner and disinfectant for between-case use in
      the operating room. We found high cleaning efficacy (84%-96%) and a high
      compliance rate with the IHP (84%). With good surface compatibility, low
      toxicity, rapid dwell time, ease of use, and excellent cleaning efficacy, the IHP
      may be considered an option for between-case cleaning and disinfection in the
      operating room.

PMID- 24939511
TI  - Innate immune-response mechanisms in dermatomyositis: an update on pathogenesis,
      diagnosis and treatment.
AB  - Dermatomyositis (DM) is an autoimmune disease mainly affecting muscle and skin.
      Typical clinical and laboratory findings include muscle weakness with elevated
      muscle enzymes, characteristic skin lesions (e.g., Gottron papules, heliotrope
      erythema, Shawl sign), and specific serum autoantibodies. Recent studies have
      highlighted the activation of the innate immune system, including high expression
      of interferons (IFNs) and IFN-regulated proteins, as an important pathological
      hallmark of DM. These findings have changed our understanding of the disease
      fundamentally, since inappropriate activation of the innate immune system with
      secondary dysregulation of the adaptive immune response is now considered to be a
      central pathogenetic feature of DM. In this article, we review current guidelines
      and standards in diagnosis and treatment. We detail evidence-based and
      pathophysiology-based treatment strategies, with a focus on skin as well as on
      muscle lesions. Particularly, we discuss how the recent advances in the
      understanding of the pathomechanisms of DM have altered our conception of the
      mode of action of established drugs such as chloroquine and methotrexate.
      Finally, we outline possible future treatment strategies, with a focus on the
      innate immune system, e.g., targeting the IFN system with the anti-IFN-alpha
      antibody sifalimumab. 

PMID- 24939515
TI  - A carbapenem-resistant Klebsiella pneumoniae outbreak following bronchoscopy.

PMID- 24939516
TI  - Health care workers--part of the system or part of the public? Ambivalent risk
      perception in health care workers.
AB  - BACKGROUND: The emergence of the avian influenza A (H7N9) in China during 2013
      illustrates the importance of health care professionals as a mediating channel
      between health agencies and the public. Our study examined health care
      professionals' risk perceptions considering their unique position as representing
      the health care system and yet also being part of the public, hence a risk group.
      Recent studies have examined the role of health professionals' personal risk
      perceptions and attitudes regarding compliance of the general public with
      vaccination. Our study examined how risk perception affects their risk analysis.
      METHODS: We employed an online survey of Israeli health care professionals and
      the general public in Israel (N = 240). RESULTS: When risk perception is
      relatively low, health care professionals tend to base their attitudes toward
      vaccines on analytical knowledge (Rc = 0.315; P < .05), whereas in situations
      with high risk perception, the results did not indicate any significant
      difference between Israeli health professionals and the Israeli general public,
      hence both groups base their attitudes more on emotions and personal experience
      than on analytical knowledge. CONCLUSIONS: Public health organizations must
      consider the fact that health professionals are a group that cannot be
      automatically treated as an extension of the organization. When the risk is
      tangible and relevant, health care workers behave and act like everybody else.
      Our study contributes to understanding health care professionals' perceptions
      about vaccines and the thinking processes underlying such perceptions.

PMID- 24939517
TI  - Measles investigation: a moving target.
AB  - Measles is a highly contagious respiratory infection with significant
      transmission risk once thought to be on the verge of elimination. Outbreaks in
      Europe have resulted in resurgence; however, experience with measles is limited
      in the United States. We describe the impact of 2 measles cases presenting to our
      emergency department in May 2011. Exposure criteria were defined and revised.
      Guidance documents were developed and distributed. Suspect cases were masked and
      escorted to negative pressure. Lack of prompt IgM and polymerase chain reaction
      testing resulted in delayed disease confirmation. Computerized flagging systems
      were established. Exposed individuals were screened to determine the need for
      prophylaxis. Investigation costs were calculated. A total of 171 patients and
      visitors and 94 employees met exposure criteria. Employees had proof of immunity
      to measles. Of these, 43 patients and visitors returned for prophylaxis. No
      subsequent transmission occurred. The conservative cost for these investigations
      was $63,176.39. Multiple challenges were identified. Inexperience with measles
      can result in significant outbreaks. Although transmission did occur at another
      facility, it was prevented at our facility because of rapid case recognition,
      isolation, health care worker immunity, and multidisciplinary response.
      Discordance between the Healthcare Infection Control Practices Advisory Committee
      and public health guidelines for measles control created unnecessary challenges. 

PMID- 24939518
TI  - Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic
      enzymes, and immunity in streptozotocin induced diabetes mellitus.
AB  - BACKGROUND: Nigella sativa fixed (NSFO) and essential (NSEO) oils have been used
      to treat diabetes mellitus and its complications. Present study was undertaken to
      explore and validate these folkloric uses. METHODS: Sprague dawley rats having
      streptozotocin (STZ) induced diabetes mellitus were used to assess the role of
      NSFO and NSEO in the management of diabetes complications. Parameters
      investigated were antioxidant potential, oxidative stress, and the immunity by in
      vivo experiments. RESULTS: The results indicated that STZ decreased the
      glutathione contents (25.72%), while NSFO and NSEO increased the trait
      significantly (P < 0.05). Experimental diets increased the tocopherol contents (P
      < 0.01) and enhanced the expression of hepatic enzymes (P < 0.01). Correlation
      matrix further indicated that antioxidant potential is positively associated (P <
      0.05) responsible for the modulation of hepatic enzymes and the decrease of the
      nitric oxide production thus controlling the diabetes complications. CONCLUSIONS:
      Overall, results of present study supported the traditional use of N. sativa and
      its derived products as a treatment for hyperglycemia and allied abnormalities.
      Moreover, N. sativa fixed and essential oils significantly ameliorate free
      radicals and improve antioxidant capacity thus reducing the risk of diabetic
      complications.

PMID- 24939519
TI  - Quantitative change of EEG and respiration signals during mindfulness meditation.
AB  - BACKGROUND: This study investigates measures of mindfulness meditation (MM) as a
      mental practice, in which a resting but alert state of mind is maintained. A
      population of older people with high stress level participated in this study,
      while electroencephalographic (EEG) and respiration signals were recorded during
      a MM intervention. The physiological signals during meditation and control
      conditions were analyzed with signal processing. METHODS: EEG and respiration
      data were collected and analyzed on 34 novice meditators after a 6-week
      meditation intervention. Collected data were analyzed with spectral analysis,
      phase analysis and classification to evaluate an objective marker for meditation.
      RESULTS: Different frequency bands showed differences in meditation and control
      conditions. Furthermore, we established a classifier using EEG and respiration
      signals with a higher accuracy (85%) at discriminating between meditation and
      control conditions than a classifier using the EEG signal only (78%). CONCLUSION:
      Support vector machine (SVM) classifier with EEG and respiration feature vector
      is a viable objective marker for meditation ability. This classifier should be
      able to quantify different levels of meditation depth and meditation experience
      in future studies.

PMID- 24939520
TI  - Selectivity in fragmentation of N-methylacetamide after resonant K-shell
      excitation.
AB  - The fragmentation pattern of the peptide model system, N-methylacetamide, is
      investigated using ion time-of-flight (TOF) spectroscopy after resonant K-shell
      excitation. Corresponding near-edge X-ray absorption fine structure (NEXAFS)
      spectra recorded at high resolution at the C1s, N1s and O1s edges are presented.
      Analysis of the ion TOF data reveals a multitude of fragmentation channels and
      dissociation pathways. Comparison between the excitation of six different
      resonances in the vicinity of the C1s, N1s and O1s edges suggests evidence for
      site-selective bond breaking. In particular the breaking of the peptide bond and
      the N-C(alpha) bond show a clear correlation with resonant excitation at the N1s
      edge. Also, stronger tendencies towards site-selective bond breaking are found
      for the generation of single ions compared with ion pairs. Analysis of angular
      distributions of ions from breakage of the peptide bond yields a fragmentation
      time of <400 fs.

PMID- 24939521
TI  - Chemotherapy only in early-stage Hodgkin lymphoma: more relapses but "same" (or
      possibly worse) survival--reconsidering the misguided trend to omit radiotherapy.
AB  - The standard treatment of early-stage Hodgkin lymphoma (ESHL) as recommended by
      most national guidelines is combined modality treatment (CMT) that includes a
      short course ABVD followed by a small field of low dose radiotherapy (RT).
      Recently a trend to treat patients with more chemotherapy alone has been promoted
      by some claiming that chemotherapy alone is good enough, and the overall survival
      is similar. These arguments need to be carefully examined, and the risk of more
      chemotherapy upfront and salvage considered. The suggestion that interim PET will
      identify patients that can have similar results with chemotherapy alone has
      recently been questioned by the results of both European and UK studies. It is
      the subject of this critical review. 

PMID- 24939522
TI  - Beyond standard polysomnography: advantages and indications for use of extended
      10-20 EEG montage during laboratory sleep study evaluations.
AB  - PURPOSE: Standard polysomnography (PSG) typically utilizes 4-6 channels of
      electroencephalography (EEG), which is inadequate to evaluate focal epileptiform
      activity. Though technical capability has long existed for more extensive EEG
      recording, few sleep laboratories have utilized this technique. The objective of
      this study was to determine the utility of combining PSG with 18-channel EEG in
      select patients with paroxysmal nocturnal events or other symptoms concerning for
      sleep disorders, nocturnal seizures or both. METHODS: Consecutive combined PSG
      EEG studies (n=237) were performed between 10/1/2005 and 8/1/2009. Demographics,
      referral source, indications, and results were reviewed and analyzed. RESULTS: Of
      the 237 consecutive combined PSG-EEG studies performed, 93% revealed the presence
      of a primary sleep disorder, 38% were shown to have abnormal EEGs, and 37% had
      both. Among the 221 subjects (93%) shown to have sleep disorders, the majority of
      these cases were obstructive sleep apnea (OSA) 89%, followed by periodic limp
      movements of sleep (PLMS) 22% and rapid eye movement behavior disorder (RBD) 6%.
      Significantly more patients with known epilepsy were diagnosed with OSA then were
      patients without a seizure history. CONCLUSIONS: Combined PSG-EEG, utilizing 18
      channel EEG, is an under-utilized technique which can assist in diagnosing
      paroxysmal nocturnal events, and differentiate between the presence of a primary
      sleep disorder, seizure activity, or both. Our study further illustrates the
      importance of considering sleep disorders in epilepsy patients.

PMID- 24939523
TI  - Predictive value of EEG findings at control of epileptic spasms for seizure
      relapse in patients with West syndrome.
AB  - PURPOSE: To evaluate the prognostic importance of electroencephalography (EEG)
      findings at cessation of epileptic spasms for seizure outcome. METHODS: We
      reviewed 71 children with West syndrome (cryptogenic 14) who had obtained control
      of epileptic spasms with initial treatment (adrenocorticotropic hormone (ACTH)
      37, high-dose vitamin B6 2, and antiepileptic drugs 32). According to the EEG
      findings at control of epileptic spasms, the subjects were divided into three
      groups: normal group (no epileptic activity, n=12), abnormal group (residual
      epileptic activity without hypsarrhythmia, n=53), and hypsarrhythmic group
      (persisting hypsarrhythmia, n=6). RESULTS: Overall, 47 (66%) of the 71 patients
      (cryptogenic 4) had experienced relapses of seizures (epileptic spasms 23 and
      focal seizure 24) after initial control of epileptic spasms. Within symptomatic
      cases, seizure relapse rate varied widely from 0% (Down syndrome) to 100%
      (tuberous sclerosis), depending on underlying causes. Seizure relapse depended on
      the EEG findings at control of epileptic spasms. The normal group had a
      significantly lower seizure relapse rate (17%) in comparison with the abnormal
      group (75%), the hypsarrhythmic group (83%), and the epileptiform (abnormal plus
      hypsarrhythmic, 76%) group. No significant difference in seizure relapse rate was
      observed between non-hypsarrhythmic (normal plus abnormal, 65%) and
      hypsarrhythmic groups. At the last follow-up, normal group children also showed a
      favorable seizure prognosis (seizure control 100%). CONCLUSIONS: A favorable
      seizure prognosis is associated with the disappearance of epileptic activity, but
      not the resolution of hypsarrhythmic pattern on EEG at control of epileptic
      spasms. We suggest that effective treatment for West syndrome should produce both
      cessation of epileptic spasms and disappearance of epileptic activity on EEG.

PMID- 24939524
TI  - Prevalence and risk factors of epilepsy among school children in Kayseri City
      Center, an urban area in Central Anatolia, Turkey.
AB  - PURPOSE: To investigate the prevalence of epilepsy in schoolchildren aged 7-17 in
      the province of Kayseri together with the accompanying risk factors. METHODS: Ten
      thousand individuals selected using the "stratified cluster sampling method" from
      a total population of 259,428 students within the borders of Kayseri city center
      constituted the study sample. A questionnaire was prepared in line with the
      epidemiological studies protocol recommended by the International Epilepsy Union
      Epidemiology and Prognosis Committee in 1993. Data were analyzed on IBM SPSS
      Statistics 20. Significance was set at p<0.05. RESULTS: Of the 15,000
      questionnaires distributed, 72% (n=10,742) were returned fully completed. Eighty
      three students had been or were still being monitored with a diagnosis of
      epilepsy. The raw prevalence of epilepsy was 6/1000 in females, 9/1000 in males
      and 8/1000 in both groups together. Prevalence of active epilepsy was 4/1000 in
      females, 7/1000 in males and 6/1000 in both groups together. Premature birth
      increased the risk of epilepsy 2.6 times, and average and poor family income
      levels increased the risk of epilepsy 3.3 and 1.6 times, respectively. A history
      of febrile convulsion increased the risk of epilepsy 15.1 times. CONCLUSION: The
      prevalence of epilepsy in the 7-17 age group in Kayseri is closer to that in
      developed rather than developing countries. We conclude that the risk factors for
      epilepsy, and particularly febrile convulsion, and the true prevalence rates need
      to be determined through studies involving wide socioeconomic strata.

PMID- 24939525
TI  - [War of languages will not occur].

PMID- 24939526
TI  - [The Jekyll and Hyde sides of happiness or the strange case of psychosocial
      genomics].

PMID- 24939528
TI  - [Opening the brain to new therapies].

PMID- 24939527
TI  - [Unexpected complexity of the Drosophila digestive tract: towards a model for
      functional regionalization].

PMID- 24939529
TI  - [Recurrent mutations in RHOA and FYN in peripheral T cell lymphomas].

PMID- 24939530
TI  - [Sphingosine 1-phosphate as a biomarker for Alzheimer's disease?].

PMID- 24939531
TI  - [Chronicle of a death foretold: endoplasmic reticulum stress and beta cell
      apoptosis in diabetes].

PMID- 24939532
TI  - [Mycobacterial cording: a new mechanism of immune evasion?].

PMID- 24939533
TI  - [Tracking the adenovirus intracellular route during the early steps of the
      infectious cycle].

PMID- 24939534
TI  - [Lymphangiogenic gene expression adaptation in tumor hypoxic environment].

PMID- 24939535
TI  - [HIV-1 cell-to-cell transmission and broadly neutralizing antibodies].

PMID- 24939537
TI  - [KCC2: a new therapeutical target for the treatment of neurological diseases].

PMID- 24939536
TI  - [Crucial role of CD4 and CD8 coreceptors in antigen recognition of alphabetaT
      lymphocytes].

PMID- 24939538
TI  - [New physiopathological roles for the PLA2R1 receptor in cancer and membranous
      nephropathy].
AB  - PLA2R1 is a large transmembrane receptor of 180-kDa that belongs to the
      superfamily of C-type lectins. It was discovered because of its high affinity for
      secreted phospholipases A2 (sPLA2), enzymes that play a key role in lipid
      mediator synthesis. Early PLA2R1 physiological roles include the clearance of
      sPLA2 from the extracellular medium and/or promotion of their actions. Over the
      last four years, two independent studies suggested that PLA2R1 plays a role in
      cancer as a tumor gene suppressor and is the major target antigen of auto-immune
      antibodies involved in idiopathic membranous nephropathy, a severe human kidney
      disease. These novel findings shed light on PLA2R1 and pave the way for its use
      as a reliable biomarker and an attractive therapeutic target in these diseases. 

PMID- 24939539
TI  - [Lp-PLA2 and sPLA2: cardiovascular biomarkers].
AB  - Phospholipases A2 (PLA2) belong to a superfamily of enzymes that catalyze the
      hydrolysis of glycerophospholipids at the sn-2 position, producing nonesterified
      fatty acids and lysophospholipids. Many experimental studies have shown that PLA2
      are involved in lipid metabolism and immuno-inflammatory response and participate
      in the development of atherosclerosis. In humans, therapeutic approaches based on
      the inhibition of PLA2 are currently in development. This review summarizes human
      studies regarding the prognostic value of two members of the family of PLA2, Lp
      PLA2 (lipoprotein-associated PLA2) and sPLA2 (secretory PLA2), in cardiovascular
      diseases. 

PMID- 24939540
TI  - [SIRT2, a multi-talented deacetylase].
AB  - Sirtuin 2 (SIRT2) is an NAD(+) (nicotinamide adenine dinucleotide)-dependent
      deacetylase. Studies of this protein have often been divergent, highlighting the
      dependence of pleiotropic effects of SIRT2 on cellular context. The natural
      polyphenol resveratrol is known to exert opposite actions on neural cells
      according to their normal or cancerous status. We have recently shown the
      involvement of SIRT2 in the antiproliferative effects of resveratrol on primary
      cultures of human glioblastoma stem cells. SIRT2 could become a new therapeutic
      target. 

PMID- 24939542
TI  - [Miraculous catch by neutrophils NETs].
AB  - Neutrophil extracellular traps (NET) account for a new mechanism of anti
      infectious innate immunity that may lead to important tissue damages. Indeed, a
      growing number of studies demonstrate the involvement of NET in the pathogenesis
      of several human diseases as diverse as autoimmune diseases, thrombotic disorders
      or some inflammatory diseases. After a short description of molecular mechanisms
      of NETosis and its host-defense function, we will review their detrimental
      effects. We will then examine the potential therapeutic approaches for modulating
      excessive or inappropriate NETosis and thereby minimize tissue injury. 

PMID- 24939541
TI  - [Nectins and nectin-like receptors DNAM-1 and CRTAM: new ways for tumor escape].
AB  - Nectin and nectin-like (Necl) are cell adhesion molecules expressed in various
      tumors. They were alternatively reported as involved in tumor suppressor or
      oncogenic functions that led to their use as histological or serological cancer
      markers. Gene inactivation in lung carcinoma but overexpression in leukemia were
      reported for Necl-2. DNAM-1 and CRTAM are emerging NK receptors of immune cells
      that were described to interact with nectin and Necl. DNAM-1, constitutively
      expressed by CD8(+) T cells, NK or gammadelta T lymphocytes, is a ligand of Necl
      5. It participates to tumor immunosurveillance promoting Necl-5 expressing tumor
      cell lysis. CRTAM, only expressed after lymphocyte activation, is a ligand of
      Necl-2. Engagement of CRTAM with Necl-2 has opposite effects depending on the
      type of lymphocyte. For NK or CD8(+) T cells, it promotes cytotoxicity and
      IFNgamma secretion favoring immunosurveillance. By contrast, CRTAM/Necl-2
      interaction triggers cell death of activated TVg9Vd2 gammadelta T cells favoring
      immune escape. Nectin and Necl-mediated interactions appear to be crucial for the
      delicate balance between tumor escape and antitumor response. 

PMID- 24939543
TI  - [Pediatric HIV infections in developed countries: current situation and future
      challenges].
AB  - In 2013, approximately 1500 HIV-infected children are followed in France.
      Antiretroviral therapy (ART) has greatly improved the survival of these children,
      whose long-term clinical outcomes are encouraging in high-resources countries.
      However, paediatricians continue to face difficulties for these children: missed
      opportunities for early HIV testing (especially in immigrant children born in Sub
      Saharan African countries), high rates of virological failure in ART-experienced
      children, lack of studies evaluating the long-term toxicity of ART in perinatally
      HIV-infected patients. Future challenges will imply to study to what extent very
      early ART in infants may alter the establishment of HIV infection and improve the
      long-term immunological and virological outcome of these children. 

PMID- 24939545
TI  - [Biotherapies, immunotherapies, targeted therapies, biopharmaceuticals... which
      word should be used?].
AB  - The ability to accurately describe and name medical advances is a prerequisite to
      foster public debates with scientists and physicians, and favour faith over fear
      among patients and citizens. Therapeutic antibodies are a good example of a
      medical breakthrough which has met with considerable clinical success, and which
      terminology has changed over the years. If the appellation serotherapy was
      appropriate a century ago, it has become obsolete. Recent names such as
      biotherapy, immunotherapy, targeted therapy, biopharmaceuticals have been
      introduced and are now commonly used, each of those can apply to therapeutic
      antibodies. It is thus interesting to question the real meaning of these
      different appellations. Our goal in this manuscript is to analyse the genesis of
      these terms but also to suggest how to simplify the terminology: biotherapy or
      targeted therapy need to be eliminated, as well as immunotherapy when
      communicating with non scientific public. It is recommended to favour the term
      biopharmaceuticals (biomedicaments in French), which clearly indicates the origin
      of these molecules, intermediate between chemical drugs and living biologics,
      whose borders need to be accurately defined also. 

PMID- 24939544
TI  - [Analysis of oncogenic signaling induced by tyrosine kinases in tumors by SILAC
      based quantitative proteomic approach].
AB  - Protein tyrosine kinases (TK) transmit intracellular signaling induced by many
      extracellular stimuli resulting in cell growth or adhesion. Deregulation of their
      activity leads to malignant cell transformation that plays an important role in
      human cancer. The signaling pathways involved in this oncogenic process are
      however only partially elucidated. Interestingly, SILAC-based quantitative
      proteomics allow the identification of the whole spectrum of TK substrates and
      the dynamic of phosphorylation state involved in oncogenic signaling. For
      example, this approach has highlighted the unsuspected complexity of the
      oncogenic signaling induced by the TK Src in colorectal cancer (CRC) cells. In
      this review, we describe a new SILAC-based technology applied to in vivo models
      of human tumors engrafted in nude mice. This method revealed significant
      differences between Src-oncogenic signaling of CRC cells in tumors and in
      culture. Finally, we discuss the interest of SILAC with recently described in
      vivo proteomic methods and in cancer, including the analysis of oncogenic
      signaling in tumor progression and the anti-tumoral activity of TK inhibitors in
      vivo. 

PMID- 24939546
TI  - [Academic cell therapy facilities are challenged by European regulation on
      advanced therapy medicinal products].
AB  - Regulation (EC) n degrees  1394/2007 from the European Parliament and the Council
      describes a new category of health products termed " Advanced Therapy Medicinal
      Products " (ATMPs). ATMPs derive from cell engineering, tissue engineering or
      genetic manipulations, and can in some instances be combined with medical
      devices. ATMPs are distributed and administered to patients, after biotechnology
      or pharmaceutical companies have obtained a marketing authorization that is
      granted by the European Commission on the basis of the European Medicines Agency
      (EMA) assessment. Seven years after the publication of the regulation, few of
      these therapies have received a marketing authorization, and even fewer have met
      commercial success, suggesting that a number of medical and economic issues still
      need to be sorted out in order to achieve sustainability in this field. The
      coexistence of three sets of rules for three categories of health products that
      are biologically and medically related - ATMPs, ATMPs produced under the hospital
      exemption rule, and cell therapy products (CTPs) (a specific legal category in
      France) that have long been used in hematopoietic cell transplantation -
      constitutes a complex regulatory framework. This situation raises significant
      issues for historical as well as emerging operators in this moving field that are
      discussed thereafter. 

PMID- 24939547
TI  - [Economic evaluation in healthcare].
AB  - Economics was only recently considered as a dimension of health technology
      assessment in France. Yet there are always limits in resources that we
      collectively agree to devote to health. A comparative "economic" appraisal is
      therefore needed to guide health choices and contribute to price regulation.
      Methodologies are based on the determination of incremental cost-effectiveness
      ratios compared with a reference. The interpretation of these ratios is never
      isolated from the context of the decision. Health economic evaluation is not
      involved in healthcare rationing, but it contributes to the rationality of
      decisions in the interest of the overall population. 

PMID- 24939550
TI  - Editorial.

PMID- 24939551
TI  - Commentary on Marcuzzi et al. The use of a pyrocarbon capitate resurfacing
      implant in chronic wrist disorders.

PMID- 24939552
TI  - Commentary on Bolster et al. Cubital tunnel syndrome: a comparison of an
      endoscopic technique with a minimal invasive open technique.

PMID- 24939553
TI  - Re: Rodrigues JN, Zhang W, Scammell BE, Davis TRC. What patients want from the
      treatment of Dupuytren's disease - is the Unite Rhumatologique des Affections de
      la Main (URAM) scale relevant? J Hand Surg Eur. Epub ahead of print 21 February
      2014. DOI: 10.1177/1753193414524689.

PMID- 24939554
TI  - IFSSH Scientific Committee on Congenital Conditions.

PMID- 24939555
TI  - Integrating antiretroviral therapy in methadone maintenance therapy clinics:
      service provider perceptions.
AB  - BACKGROUND: Using methadone maintenance therapy (MMT) clinics to deliver
      antiretroviral therapy (ART) is an effective strategy to promote treatment
      initiation and adherence for HIV-positive drug users. This paper describes the
      implementation barriers perceived by service providers for an intervention pilot
      designed to integrate ART services in MMT clinics. METHODS: The study was
      conducted in six MMT clinics in Sichuan province, China. Two service providers
      selected from each of the six clinics underwent training in administering ART.
      The trained providers delivered ART-related services in their clinics. A focus
      group was conducted among the service providers to assess their experiences and
      perceived challenges in delivering integrated services. RESULTS: Barriers at
      policy, institutional, provider, and client levels were identified. Policy level
      barriers included household registration restrictions and a lack of insurance
      coverage for testing expenses. Inefficient coordination between treatment sites
      and MMT clinics was an obstacle at the institutional level. Insufficient training
      and added workload were barriers at the provider level. Finally, conflict with
      daily dosing habits was identified as the primary reason that clients did not
      accept ART. CONCLUSION: Although integrating ART into MMT clinics is beneficial,
      multilevel barriers to implementation need to be addressed. This study documents
      the need for treatment transferability and insurance coverage, protection of
      client confidentiality, proper provider training, coordination with treatment
      sites, and individualized ART service for MMT clients.

PMID- 24939557
TI  - Could retinoids be a potential treatment for rheumatic diseases?
AB  - Retinoid, a derivative of vitamin A, is a general term used to describe compounds
      that bind to and activate retinoic acid receptors [RARs (RARalpha, RARbeta, and
      RARgamma)] and/or retinoid X receptors [RXRs (RXRalpha, RXRbeta, and RXRgamma)].
      They have been shown to surpress the differentiation of Th1/Th17 cells and induce
      the development of Th1/regulatory T cells. They also affect the proliferation of
      B cells as both an inducer and suppressor. Furthermore, retinoids may induce the
      maturation of dendritic cells and production of interleukin-10 from
      monocytes/macrophages. We recently demonstrated that retinoids suppressed the
      production of reactive oxygen species, the release of elastase from neutrophils
      by inhibiting mitogen-activated protein kinase signals, and both the migration
      speed and chemotaxis directionality of neutrophils. Retinoids, such as all-trans
      retinoic acid and tamibarotene, were previously shown to have positive effects on
      animal models of several rheumatic diseases, including arthritis, myositis, and
      vasculitis in vivo. Moreover, retinoids have been used in a pilot study to
      effectively treat patients with lupus nephritis and systemic sclerosis. We herein
      reviewed the effects of retinoids on immune cells, animal models of rheumatic
      diseases, and rheumatic patients.

PMID- 24939556
TI  - RNA-seq analyses of multiple meristems of soybean: novel and alternative
      transcripts, evolutionary and functional implications.
AB  - BACKGROUND: Soybean is one of the most important crops, providing large amounts
      of dietary proteins and edible oil, and is also an excellent model for studying
      evolution of duplicated genes. However, relative to the model plants Arabidopsis
      and rice, the present knowledge about soybean transcriptome is quite limited.
      RESULTS: In this study, we employed RNA-seq to investigate transcriptomes of 11
      soybean tissues, for genome-wide discovery of truly expressed genes, and novel
      and alternative transcripts, as well as analyses of conservation and divergence
      of duplicated genes and their functional implications. We detected a total of
      54,132 high-confidence expressed genes, and identified 6,718 novel
      transcriptional regions with a mean length of 372 bp. We also provided strong
      evidence for alternative splicing (AS) events for ~15.9% of the genes with two or
      more exons. Among them, 1,834 genes exhibited stage-dependent AS, and 202 genes
      had tissue-biased exon-skipping events. We further defined the conservation and
      divergence in expression patterns between duplicated gene pairs from recent whole
      genome duplications (WGDs); differentially expressed genes, tissue preferentially
      expressed genes, transcription factors and specific gene family members were
      identified for shoot apical meristem and flower development. CONCLUSIONS: Our
      results significantly improved soybean gene annotation, and also provide valuable
      resources for functional genomics and studies of the evolution of duplicated
      genes from WGDs in soybean.

PMID- 24939558
TI  - Higher level of IL-6 in Jaccoud's arthropathy secondary to systemic lupus
      erythematosus: a perspective for its treatment?
AB  - Jaccoud's arthropathy (JA) is a condition characterized clinically by
      'reversible' joint deformities along with an absence of articular erosions on a
      plain radiograph. The main clinical entity associated with JA is systemic lupus
      erythematosus (SLE) with a prevalence of around 5 %. The aim of the present study
      was to compare the inflammatory markers including cytokine levels in blood of SLE
      patients with and without JA. Patients with diagnosis of SLE as defined by ACR
      criteria were screened and divided in two groups, one with JA and one control
      group without JA. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      complement C3 and C4 levels antinuclear antibodies (ANA), anti-dsDNA antibodies
      and serum levels of IL-2, IL-6, IL-10, IL-21, IL-22 and TNF-alpha were determined
      in all patients. Eighty female patients with SLE, 18 (22.5 %) with JA and 62
      (77.5 %) without JA, were included in this study. JA patients had higher disease
      duration (p = 0.008), ESR (p < 0.001), CRP level (p = 0.002), ANA titer (p <
      0.001) and dsDNA antibody level (p = 0.009). The serum levels of IL-2, IL-10, IL
      21, IL-22 and TNF-alpha were not significantly different between the two groups
      (p > 0.05), but the level of IL-6 was higher in JA group (p < 0.001). The serum
      level of IL-6 might have a correlation with JA secondary to SLE.

PMID- 24939559
TI  - Future directions for the investigation of intranasal oxytocin and pain: Comment
      on: Oxytocin nasal spray in fibromyalgic patients (Rheumatol Int. E-pub ahead of
      print. doi: 10.1007/s00296-014-2953-y).

PMID- 24939560
TI  - Comparative modifications in bacterial gill-endosymbiotic populations of the two
      bivalves Codakia orbiculata and Lucina pensylvanica during bacterial loss and
      reacquisition.
AB  - Until now, the culture of sulphur-oxidizing bacterial symbionts associated with
      marine invertebrates remains impossible. Therefore, few studies focused on
      symbiont's physiology under stress conditions. In this study, we carried out a
      comparative experiment based on two different species of lucinid bivalves
      (Codakia orbiculata and Lucina pensylvanica) under comparable stress factors. The
      bivalves were starved for 6 months in sulphide-free filtered seawater. For C.
      orbiculata only, starved individuals were then put back to the field, in natural
      sediment. We used in situ hybridization, flow cytometry and X-ray fluorescence to
      characterize the symbiont population hosted in the gills of both species. In L.
      pensylvanica, no decrease in symbiont abundance was observed throughout the
      starvation experiment, whereas elemental sulphur slowly decreased to zero after 3
      months of starvation. Conversely, in C. orbiculata, symbiont abundance within
      bacteriocytes decreased rapidly and sulphur from symbionts disappeared during the
      first weeks of the experiment. The modifications of the cellular characteristics
      (SSC--relative cell size and FL1--genomic content) of the symbiotic populations
      along starvation were not comparable between species. Return to the sediment of
      starved C. orbiculata individuals led to a rapid (2-4 weeks) recovery of
      symbiotic cellular characteristics, comparable with unstressed symbionts. These
      results suggest that endosymbiotic population regulation is host-species
      dependent in lucinids.

PMID- 24939562
TI  - Source identification of the Arctic sea ice proxy IP25.
AB  - Analysis of the organic geochemical biomarker IP25 in marine sediments is an
      established method for carrying out palaeo sea ice reconstructions for the
      Arctic. Such reconstructions cover timescales from decades back to the early
      Pleistocene, and are critical for understanding past climate conditions on Earth
      and for informing climate prediction models. Key attributes of IP25 include its
      strict association with Arctic sea ice together with its ubiquity and stability
      in underlying marine sediments; however, the sources of IP25 have remained
      undetermined. Here we report the identification of IP25 in three (or four)
      relatively minor (<5%) sea ice diatoms isolated from mixed assemblages collected
      from the Canadian Arctic. In contrast, IP25 was absent in the dominant taxa.
      Chemical and taxonomical investigations suggest that the IP25-containing taxa
      represent the majority of producers and are distributed pan-Arctic, thus
      establishing the widespread applicability of the IP25 proxy for palaeo Arctic sea
      ice reconstruction. 

PMID- 24939561
TI  - Elevated O3 enhances the attraction of whitefly-infested tomato plants to
      Encarsia formosa.
AB  - We experimentally examined the effects of elevated O3 and whitefly herbivory on
      tomato volatiles, feeding and oviposition preferences of whiteflies and
      behavioural responses of Encarsia formosa to these emissions on two tomato
      genotypes, a wild-type (Wt) and a jasmonic acid (JA) defence-enhanced genotype
      (JA-OE, 35S). The O3 level and whitefly herbivory significantly increased the
      total amount of volatile organic compounds (VOCs), monoterpenes, green leaf
      volatiles (GLVs), and aldehyde volatiles produced by tomato plants. The 35S
      plants released higher amount of total VOCs and monoterpene volatiles than Wt
      plants under O3+herbivory treatments. The feeding and oviposition bioassays
      showed that control plants were preferred by adult whiteflies whereas the 35S
      plants were not preferred by whiteflies. In the Y-tube tests, O3+herbivory
      treatment genotypes were preferred by adult E. Formosa. The 35S plants were
      preferred by adult E. formosa under O3, herbivory and O3+herbivory treatments.
      Our results demonstrated that elevated O3 and whitefly herbivory significantly
      increased tomato volatiles, which attracted E. formosa and reduced whitefly
      feeding. The 35S plants had a higher resistance to B. tabaci than Wt plant. Such
      changes suggest that the direct and indirect defences of resistant genotypes,
      such as 35S, could strengthen as the atmospheric O3 concentration increases.

PMID- 24939563
TI  - Late-onset bloodstream infections of Very-Low-Birth-Weight infants: data from the
      Polish Neonatology Surveillance Network in 2009-2011.
AB  - BACKGROUND: Late-Onset Bloodstream Infections (LO-BSI) continue to be one of the
      most important complications associated with hospitalization of infants born with
      very low birth weight (VLBW). The aims of this study were to assess the
      epidemiology of LO-BSI together with the risk factors and the distribution of
      causative pathogens at six Polish neonatal intensive care units that participated
      in the Polish Neonatology Surveillance Network from January 1, 2009 to December
      31, 2011. METHODS: The surveillance covered 1,695 infants whose birth weights
      were <1501 grams (VLBW) in whom LO-BSI was diagnosed >72 hours after delivery.
      Case LO-BSI patients were defined according to NeoKISS. RESULTS: Four hundred
      twenty seven episodes of LO-BSI were diagnosed with a frequency of 25.3% and an
      incidence density of 6.7/1000 patient-days (pds). Results of our multivariate
      analysis demonstrated that surgical procedures and lower gestational age were
      significantly associated with the risk of LO-BSI. Intravascular catheters were
      used in infants with LO-BSI significantly more frequently and/or for longer
      duration: Central venous cathters (CVC) (OR 1.29) and Peripheral venous catheters
      (PVC) (OR 2.8), as well as, the total duration of total parenteral nutrition (13
      vs. 29 days; OR 1.81). Occurrence of LO-BSI was significantly associated with
      increased the length of mechanical ventilation (MV) (OR 2.65) or the continuous
      positive airway pressure (CPAP) (OR 2.51), as well as, the duration of antibiotic
      use (OR 2.98). The occurrence of more than one infection was observed frequently
      (OR 9.2) with VLBW with LO-BSI. Microorganisms isolated in infants with LO-BSI
      were dominated by Gram-positive cocci, and predominantly by coagulase-negative
      staphylococci (62.5%). CONCLUSIONS: Independent risk factor for LO-BSI in VLBV
      infants are: low gestational age and requirement for surgery. The incidence rates
      of LO-BSI especially CVC-BSI were higher in the Polish NICUs surveillance than
      those of other national networks, similar to the central- and peripheral
      utilization ratio.

PMID- 24939564
TI  - The impact of human rhinovirus infection in pediatric patients undergoing heart
      surgery.
AB  - Human rhinovirus (HRV), the most common cause of upper respiratory infection in
      children, can present as bronchiolitis, pneumonia, or asthma exacerbations. The
      impact of HRV in infants and toddlers with congenital heart disease is poorly
      defined. A case-control study was performed to compare the clinical course for 19
      young children with respiratory symptoms who tested positive for rhinovirus after
      heart surgery with that of 56 matched control subjects. The control subjects were
      matched by surgical repair, age, weight, and time of the year. Patients with
      known HRVs before surgery and control subjects with respiratory symptoms or
      positive test results for viruses were excluded from the study. Human rhinovirus
      infection was associated with more than a tenfold increase in the odds of
      noninvasive ventilation after extubation (odds ratio [OR] 11.45; 95 % confidence
      interval [CI] 3.97-38.67), a 12-fold increase in the probability of extubation
      failure (OR 12.84; 95 % CI 2.93-56.29), and increased use of pulmonary
      medications including bronchodilator and nitric oxide (p < 0.001). As a result,
      the hospital length of stay (HLOS) was two times longer than for the control
      subjects (p < 0.001), and the cardiac intensive care unit (CICU) length of stay
      (CICU LOS) was three times longer (p < 0.0001). The intubation time was
      significantly longer (p < 0.001), and the CICU respiratory charges were
      significantly greater (p = 0.001) for the infected patients. Human rhinovirus
      increases resource use and prolongs postoperative recovery after pediatric heart
      surgery. Surgery timing should be delayed for patients with rhinovirus if
      possible.

PMID- 24939565
TI  - Autoimmune hepatitis in the Alaska Native population: autoantibody profile and
      HLA associations.
AB  - BACKGROUND & AIMS: The Alaska Native population is one of few populations in the
      world with a high prevalence of autoimmune hepatitis. The objective of this study
      was to determine the frequency and HLA and clinical associations of
      autoantibodies in Alaska Native people with autoimmune hepatitis. METHODS: Alaska
      Native individuals with autoimmune hepatitis were recruited in clinics conducted
      statewide. Sera were tested for the presence of autoantibodies described in
      either autoimmune hepatitis or rheumatic disease. Associations between
      autoantibodies and HLA alleles and clinical features were assessed. RESULTS:
      Seventy-one patients were included. At the study visit, 34 patients (47.9%) had
      antibodies to double-stranded DNA by immunofluorescence; 27 (38.0%) had anti
      neutrophil cytoplasmic antibodies; and 11 (15.5%) had anti-Ro antibodies. Only
      one person had antibodies against soluble liver antigen, and in that person, anti
      Ro was absent. Associations were found between autoantibodies and HLA alleles,
      including positive associations between HLA DR3 and anti-double-stranded DNA
      antibodies and between HLA DR14 and antineutrophil cytoplasmic antibodies. There
      was no association between autoantibodies and clinical outcomes. CONCLUSIONS: As
      in other populations, the prevalence of anti-double-stranded DNA antibodies and
      antineutrophil cytoplasmic antibodies is high in Alaska Native people with
      autoimmune hepatitis. In contrast to data from other populations, there is a
      lower prevalence of anti-soluble liver antigen and a lack of association between
      anti-Ro and anti-soluble liver antigen. In addition, the HLA profile and
      associations with autoantibodies are unique. No clear prognostic implications of
      autoantibodies have emerged in this population.

PMID- 24939566
TI  - Elucidation of pseurotin biosynthetic pathway points to trans-acting C
      methyltransferase: generation of chemical diversity.
AB  - Pseurotins comprise a family of structurally related Aspergillal natural products
      having interesting bioactivity. However, little is known about the biosynthetic
      steps involved in the formation of their complex chemical features. Systematic
      deletion of the pseurotin biosynthetic genes in A. fumigatus and in vivo and in
      vitro characterization of the tailoring enzymes to determine the biosynthetic
      intermediates, and the gene products responsible for the formation of each
      intermediate, are described. Thus, the main biosynthetic steps leading to the
      formation of pseurotin A from the predominant precursor, azaspirene, were
      elucidated. The study revealed the combinatorial nature of the biosynthesis of
      the pseurotin family of compounds and the intermediates. Most interestingly, we
      report the first identification of an epoxidase C-methyltransferase bifunctional
      fusion protein PsoF which appears to methylate the nascent polyketide backbone
      carbon atom in trans. 

PMID- 24939567
TI  - Characterization of a human powered nebulizer compressor for resource poor
      settings.
AB  - BACKGROUND: Respiratory disease accounts for three of the ten leading causes of
      death worldwide. Many of these diseases can be treated and diagnosed using a
      nebulizer. Nebulizers can also be used to safely and efficiently deliver
      vaccines. Unfortunately, commercially available nebulizers are not designed for
      use in regions of the world where lung disease is most prevalent: they are
      electricity-dependent, cost-prohibitive, and not built to be reliable in harsh
      operating conditions or under frequent use.To overcome these limitations, the
      Human Powered Nebulizer compressor (HPN) was developed. The HPN does not require
      electricity; instead airflow is generated manually through a hand-crank or
      bicycle-style pedal system. A health care worker or other trained individual
      operates the device while the patient receives treatment.This study demonstrates
      functional specifications of the HPN in comparison with a standard commercially
      available electric jet nebulizer compressor, the DeVilbiss Pulmo-Aide 5650D
      (Pulmo-Aide). METHODS: Pressure and flow characteristics were measured with a
      rotameter and pressure transducer, respectively. Volume nebulized by each
      compressor was determined by mass, and particle size distribution was determined
      via laser diffraction. The Hudson RCI Micro Mist nebulizer mouthpiece was used
      with both compressors. RESULTS: The pressure and flow generated by the HPN and
      Pulmo-Aide were: 15.17 psi and 10.5 L/min; and 14.65 psi and 11.2 L/min,
      respectively. The volume of liquid delivered by each was equivalent, 1.097 +/-
      0.107 mL (mean +/- s.e.m., n = 13) for the HPN and 1.092 +/- 0.116 mL for the
      Pulmo-Aide. The average particle size was also equivalent, 5.38 +/- 0.040
      micrometers (mean +/- s.e.m., n = 7) and 5.40 +/- 0.025 micrometers,
      respectively. CONCLUSIONS: Based on these characteristics, the HPN's performance
      is equivalent to a popular commercially available electric nebulizer compressor.
      The findings presented in this paper, combined with the results of two published
      clinical studies, suggest that the HPN could serve as an important diagnostic and
      therapeutic tool in the fight against global respiratory health challenges
      including: tuberculosis, chronic obstructive pulmonary disease, asthma, and lower
      respiratory infections.

PMID- 24939568
TI  - Two plasmid-encoded genes of enteropathogenic Escherichia coli strain K798
      promote invasion and survival within HEp-2 cells.
AB  - Enteropathogenic Escherichia coli (EPEC) are considered to be extracellular
      pathogens, inducing attaching and effacing lesions following their attachment to
      the surface of eukaryotic cells; however, in vitro and in vivo invasion by EPEC
      has been reported in several studies. A cloned 4.6 kb fragment of EPEC plasmid
      pLV501 has been shown to facilitate invasion of E. coli K-12, and here we further
      investigate the nature of this process. Two of the three complete open reading
      frames contained within the plasmid fragment have been cloned to E. coli, and in
      HEp-2 adherence assays both tniA2 and pecM were shown to be expressed during the
      first 3 h of infection from a plac promoter. Escherichia coli transformants
      carrying pecM alone or in combination with tniA2 were able to both survive
      intracellularly and escape eukaryotic cells to re-establish themselves within the
      medium, whereas those bacterial cells carrying tniA2 alone could not be isolated
      from within HEp-2 cells after 24 h of infection, but were present in the
      previously sterile medium surrounding the cells. Bacteria carrying pecM and tniA2
      adhered to HEp-2 cells with sites of adhesion characterized by underlying actin
      polymerization. The invasive potential conferred by these genes may give EPEC
      strains a survival advantage during prolonged infection. 

PMID- 24939570
TI  - Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through
      monocyte chemotactic protein-1 induction of microRNA-21.
AB  - OBJECTIVES: Endothelial progenitor cells (EPCs) circulate with increased numbers
      in the peripheral blood of patients with highly-vascularised hepatocellular
      carcinoma (HCC) and contribute to angiogenesis and neovascularisation. We
      hypothesised that angiogenic EPCs, that is, colony forming unit-endothelial cells
      (CFU-ECs), and outgrowth EPCs, that is, endothelial colony-forming cells, may
      exert paracrine effects on the behaviours and metastatic capacities of human
      hepatoma cells. DESIGN: Various molecular and functional approaches ranging from
      in vitro cell culture studies on molecular signalling to in vivo investigations
      on cell invasion and orthotropic transplantation models in mice and clinical
      specimens from patients with HCC were used. RESULTS: Monocyte chemotactic protein
      1 (MCP-1) was identified as a critical mediator released from CFU-ECs to
      contribute to the chemotaxis of Huh7 and Hep3B cells by inducing their microRNA
      21 (miR-21) biogenesis through the C-C chemokine receptor-2/c-Jun N-terminal
      kinase/activator protein-1 signalling cascade. CFU-EC-induction of miR-21 in
      these cells activated their Rac1 and matrix metallopeptidase-9 by silencing Rho
      GTPase-activating protein-24 and tissue inhibitor of metalloproteinase-3,
      respectively, leading to increased cell mobility. MCP-1-induction of miR-21
      induced epithelial-mesenchymal transformation of Huh7 cells in vitro and their
      intrahepatic metastatic capability in vivo. Moreover, increased numbers of MCP
      1(+) EPCs and their positive correlations with miR-21 induction and metastatic
      stages in human HCC were found. CONCLUSIONS: Our results provide new insights
      into the complexity of EPC-HCC interactions and indicate that anticancer
      therapies targeting either the MCP-1 released from angiogenic EPCs or the miR-21
      biogenesis in HCC cells may prevent the malignant progression of primary tumours.

PMID- 24939571
TI  - The HLA-DQ2 genotype selects for early intestinal microbiota composition in
      infants at high risk of developing coeliac disease.
AB  - OBJECTIVE: Intestinal dysbiosis has been associated with coeliac disease (CD),
      but whether the alterations are cause or consequence of the disease is unknown.
      This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is
      an independent factor influencing the early gut microbiota composition of healthy
      infants at family risk of CD. DESIGN: As part of a larger prospective study, a
      subset (n=22) of exclusively breastfed and vaginally delivered infants with
      either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8
      carriers) of developing CD were selected from a cohort of healthy infants with at
      least one first-degree relative with CD. Infant faecal microbiota was analysed by
      16S rRNA gene pyrosequencing and real time quantitative PCR. RESULTS: Infants
      with a high genetic risk had significantly higher proportions of Firmicutes and
      Proteobacteria and lower proportions of Actinobacteria compared with low-risk
      infants. At genus level, high-risk infants had significantly less Bifidobacterium
      and unclassified Bifidobacteriaceae proportions and more Corynebacterium,
      Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified
      Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also
      revealed lower numbers of Bifidobacterium species in infants with high genetic
      risk than in those with low genetic risk. In high-risk infants negative
      correlations were identified between Bifidobacterium species and several genera
      of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium).
      CONCLUSIONS: The genotype of infants at family risk of developing CD, carrying
      the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This
      finding suggests that a specific disease-biased host genotype may also select for
      the first gut colonisers and could contribute to determining disease risk.

PMID- 24939572
TI  - Reversible albumin conjugation for improved molecular imaging.

PMID- 24939574
TI  - The European Histamine Research Society 43rd Annual Meeting, May 7-10, 2014,
      Lyon, France.

PMID- 24939575
TI  - The impact of cerebellar disorders on musical ability.
AB  - BACKGROUND: The cerebellum contributes not only to motor coordination but also to
      cognitive processing. Emphasizing the cerebro-cerebellar connectivity, present
      literature declares a decisive role of the cerebellum in music perception.
      METHODS: Patients with cerebellar disorders (n=15) due to infarction or
      genetically caused degeneration were tested on their musical ability and compared
      to matched healthy control subjects. We used a validated and standardized test of
      musical ability including the reproduction of rhythm and meter, melody
      comparison, emotion identification, pitch discrimination and the recognition of
      familiar melodies. RESULTS: The patient group presented significantly lower
      scores in the subtests meter, melody comparison and emotion identification as
      compared to healthy control subjects. Rhythm reproduction and pitch
      discrimination were not affected by cerebellar disorders. DISCUSSION: Testing
      musical ability in cerebellar disorders may serve as an additional tool to detect
      and quantify cognitive deficits, namely for music perception. As a consequence,
      it might be that musical stimulation can be helpful in cognitive impairment due
      to cerebellar lesions.

PMID- 24939573
TI  - Time-dependent and somatically acquired mitochondrial DNA mutagenesis and
      respiratory chain dysfunction in a scleroderma model of lung fibrosis.
AB  - Reactive oxygen species (ROS) have been implemented in the etiology of pulmonary
      fibrosis (PF) in systemic sclerosis. In the bleomycin model, we evaluated the
      role of acquired mutations in mitochondrial DNA (mtDNA) and respiratory chain
      defects as a trigger of ROS formation and fibrogenesis. Adult male Wistar rats
      received a single intratracheal instillation of bleomycin and their lungs were
      examined at different time points. Ashcroft scores, collagen and TGFbeta1 levels
      documented a delayed onset of PF by day 14. In contrast, increased malon
      dialdehyde as a marker of ROS formation was detectable as early as 24 hours after
      bleomycin instillation and continued to increase. At day 7, lung tissue acquired
      significant amounts of mtDNA deletions, translating into a significant
      dysfunction of mtDNA-encoded, but not nucleus-encoded respiratory chain subunits.
      mtDNA deletions and markers of mtDNA-encoded respiratory chain dysfunction
      significantly correlated with pulmonary TGFbeta1 concentrations and predicted PF
      in a multivariate model.

PMID- 24939576
TI  - A novel KIF5A mutation in an Italian family marked by spastic paraparesis and
      congenital deafness.
AB  - Hereditary spastic paraplegia (HSP) includes a group of diseases characterized by
      progressive spastic weakness of the lower limbs (pure forms) with possible
      additional signs (complicated forms). The SPG10 form is due to alteration in the
      kinesin1A gene (KIF5A) that encodes the neuronal kinesin heavy chain, a protein
      required for the anterograde axonal transport. We performed clinical,
      neurophysiological and molecular studies in two siblings affected by AD-HSP
      complicated by deafness. The screening of the KIF5A gene revealed the novel
      mutation p.Leu259Gln in two affected siblings and in their father with a pure
      form of HSP.

PMID- 24939578
TI  - Structural characterization and functional validation of aldose reductase from
      the resurrection plant Xerophyta viscosa.
AB  - Aldose reductases are key enzymes in the detoxification of reactive aldehyde
      compounds like methylglyoxal (MG) and malondialdehyde. The present study
      describes for first time the preliminary biochemical and structural
      characterization of the aldose reductase (ALDRXV4) enzyme from the resurrection
      plant Xerophyta viscosa. The ALDRXV4 cDNA was expressed in E. coli using pET28a
      expression vector, and the protein was purified using affinity chromatography.
      The recombinant protein showed a molecular mass of ~36 kDa. The K M (1.2 mM) and
      k cat (14.5 s(-1)) of the protein determined using MG as substrate was found to
      be comparable with other reported homologs. Three-dimensional structure
      prediction based on homology modeling suggested several similarities with the
      other aldose reductases reported from plants. Circular dichroism spectroscopy
      results supported the bioinformatic prediction of alpha-beta helix nature of
      aldose reductase proteins. Subcellular localization studies revealed that the
      ALDRXV4-GFP fusion protein was localized both in the nucleus and the cytoplasm.
      The E. coli cells overexpressing ALDRXV4 exhibited improved growth and showed
      tolerance against diverse abiotic stresses induced by high salt (500 mM NaCl),
      osmoticum (10 % PEG 6000), heavy metal (20 mM CdCl2), and MG (5 mM). Based on
      these results, we propose that ALDRXV4 gene from X. viscosa could be a potential
      candidate for developing stress-tolerant crop plants.

PMID- 24939577
TI  - Comparison of strategies for the production of FMDV empty capsids using the
      baculovirus vector system.
AB  - Recombinant FMDV empty capsids have been produced in insect cells and larvae
      using the baculovirus expression system, although protein yield and efficiency of
      capsid assembly have been highly variable. In this work, two strategies were
      compared for the expression of FMDV A/Arg/01 empty capsids: infection with a dual
      promoter baculovirus vector coding for the capsid precursor (P12A) and the
      protease 3C under the control of the polyhedrin and p10 promoters, respectively
      (BacP12A-3C), or a single-promoter vector coding the P12A3C cassette (BacP12A3C).
      Expression levels and assembly into empty capsids were analyzed in insect cells
      and larvae. We observed that the use of the single-promoter vector allowed higher
      levels of expression both in insect cells and larvae. Recombinant capsid proteins
      produced by both vectors were recognized by monoclonal antibodies (mAbs) directed
      against conformational epitopes of FMDV A/Arg/01 and proved to self-assemble into
      empty capsids (75S) and pentamers (12S) when analyzed by sucrose gradient
      centrifugation. 

PMID- 24939579
TI  - Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation
      injury to the nucleus of the abducens nerve.
AB  - There is increasing evidence that neuronal cell death occurs via extrinsic (death
      receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase
      activation fundamentally via the mitochondrial pathway. Caspases are the key
      regulators of apoptosis. Healthy male Sprague-Dawley rats were used in the
      present study to examine the radioprotective effect of a type of pan-caspase
      inhibitor, z-VAD-fmk, following radiation, to investigate the effects of caspase
      blockade in a model of the nucleus of the abducens nerve. z-VAD-fmk was injected
      intracerebroventricularly as a bolus injection (0.2 ug/h for 1 h) into rats prior
      to exposure to radiation. Irradiation was conducted at room temperature at a dose
      of radiation of 4 Gy. The present study performed immunohistochemistry, terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot
      analysis and identified no significant changes in the expression of the X-linked
      inhibitor of apoptosis protein (XIAP) following radiation (P>0.05). As compared
      with the radiation alone group, the quantification of TUNEL-positive neurons was
      reduced in z-VAD-fmk-treated animals following radiation (P<0.01). Inhibition of
      caspase induced by z-VAD-fmk reduced the expression and activation of caspase-3, 
      8 and -9 (P<0.01). z-VAD-fmk effectively prevented radiation-induced apoptosis
      and this caspase inhibitor may be a potential therapeutic target in the treatment
      of brain radiation injury. The nucleus of the abducens nerve may be used as a
      radiation injury model, providing visual information and data on the apoptotic
      morphology of the abducens nucleus.

PMID- 24939582
TI  - Hiatal hernias or paraesophageal hernias?

PMID- 24939581
TI  - Motion control of the ankle joint with a multiple contact nerve cuff electrode: a
      simulation study.
AB  - The flat interface nerve electrode (FINE) has demonstrated significant capability
      for fascicular and subfascicular stimulation selectivity. However, due to the
      inherent complexity of the neuromuscular skeletal systems and nerve-electrode
      interface, a trajectory tracking motion control algorithm of musculoskeletal
      systems for functional electrical stimulation using a multiple contact nerve cuff
      electrode such as FINE has not yet been developed. In our previous study, a
      control system was developed for multiple-input multiple-output (MIMO)
      musculoskeletal systems with little prior knowledge of the system. In this study,
      more realistic computational ankle/subtalar joint model including a finite
      element model of the sciatic nerve was developed. The control system was tested
      to control the motion of ankle/subtalar joint angles by modulating the pulse
      amplitude of each contact of a FINE placed on the sciatic nerve. The simulation
      results showed that the control strategy based on the separation of steady state
      and dynamic properties of the system resulted in small output tracking errors for
      different reference trajectories such as sinusoidal and filtered random signals.
      The proposed control method also demonstrated robustness against external
      disturbances and system parameter variations such as muscle fatigue. These
      simulation results under various circumstances indicate that it is possible to
      take advantage of multiple contact nerve electrodes with spatial selectivity for
      the control of limb motion by peripheral nerve stimulation even with limited
      individual muscle selectivity. This technology could be useful to restore neural
      function in patients with paralysis. 

PMID- 24939583
TI  - Analyte detection with Cu-BTC metal-organic framework thin films by means of mass
      sensitive and work-function-based readout.
AB  - Metal-organic frameworks (MOFs) constitute a new generation of porous crystalline
      materials, which have recently come into focus as analyte-specific active
      elements in thin-film sensor devices. Cu-BTC--also known as HKUST-1--is one of
      the most theoretically and experimentally investigated members of the MOF family.
      Its capability to selectively adsorb different gas molecules renders this
      material a promising candidate for applications in chemical gas and vapor
      sensing. Here, we explore details of the host-guest interactions between HKUST-1
      and various analytes under different environmental conditions and study the vapor
      adsorption mechanism by mass-sensitive and work-function-based readouts. These
      complementary transduction mechanisms were successfully applied for the detection
      of low ppm (2 to 50 ppm) concentrations of different alcohols (methanol, ethanol,
      1-propanol, and 2-propanol) adsorbed into Cu-BTC thin films. Evaluation of the
      results allows for the comparison of the amounts of adsorbed vapors and the
      contribution of each vapor to the changes of the electronic properties of Cu-BTC.
      The influence of the length of the alcohol chain (C1-C3) and geometry (1
      propanol, 2-propanol) as well as their polarity on the sensing performance was
      investigated, revealing that in dry air, short chain alcohols are more likely
      adsorbed than long chain alcohols, whereas in humid air, this preference is
      changed, and the sensitivity toward alcohols is generally decreased. The
      adsorption mechanism is revealed to differ for dry and humid atmospheres,
      changing from a site-specific binding of alcohols to the open metal sites under
      dry conditions to weak physisorption of the analytes dissolved in surface
      adsorbed water reservoirs in humid air, with the signal strength being governed
      by their relative concentration.

PMID- 24939580
TI  - Thinking in circuits: toward neurobiological explanation in cognitive
      neuroscience.
AB  - Cognitive theory has decomposed human mental abilities into cognitive (sub)
      systems, and cognitive neuroscience succeeded in disclosing a host of
      relationships between cognitive systems and specific structures of the human
      brain. However, an explanation of why specific functions are located in specific
      brain loci had still been missing, along with a neurobiological model that makes
      concrete the neuronal circuits that carry thoughts and meaning. Brain theory, in
      particular the Hebb-inspired neurocybernetic proposals by Braitenberg, now offers
      an avenue toward explaining brain-mind relationships and to spell out cognition
      in terms of neuron circuits in a neuromechanistic sense. Central to this endeavor
      is the theoretical construct of an elementary functional neuronal unit above the
      level of individual neurons and below that of whole brain areas and systems: the
      distributed neuronal assembly (DNA) or thought circuit (TC). It is shown that
      DNA/TC theory of cognition offers an integrated explanatory perspective on brain
      mechanisms of perception, action, language, attention, memory, decision and
      conceptual thought. We argue that DNAs carry all of these functions and that
      their inner structure (e.g., core and halo subcomponents), and their functional
      activation dynamics (e.g., ignition and reverberation processes) answer crucial
      localist questions, such as why memory and decisions draw on prefrontal areas
      although memory formation is normally driven by information in the senses and in
      the motor system. We suggest that the ability of building DNAs/TCs spread out
      over different cortical areas is the key mechanism for a range of specifically
      human sensorimotor, linguistic and conceptual capacities and that the cell
      assembly mechanism of overlap reduction is crucial for differentiating a
      vocabulary of actions, symbols and concepts.

PMID- 24939584
TI  - Functional investigation of a QTL affecting resistance to Haemonchus contortus in
      sheep.
AB  - This study reports a functional characterization of a limited segment (QTL) of
      sheep chromosome 12 associated with resistance to the abomasal nematode
      Haemonchus contortus. The first objective was to validate the identified QTL
      through the comparison of genetically susceptible (N) and resistant (R) sheep
      produced from Martinik * Romane back-cross sheep. The R and N genotype groups
      were then experimentally infected with 10 000 H. contortus larvae and measured
      for FEC (every three days from 18 to 30 days post-challenge), haematocrit, worm
      burden and fertility. Significant differences in FEC and haematocrit drop were
      found between R and N sheep. In addition, the female worms recovered from R sheep
      were less fecund. The second step of the characterization was to investigate
      functional mechanisms associated with the QTL, thanks to a gene expression
      analysis performed on the abomasal mucosa and the abomasal lymph node. The gene
      expression level of a candidate gene lying within the QTL region (PAPP-A2) was
      measured. In addition, putative interactions between the chromosome segment under
      study and the top ten differentially expressed genes between resistant MBB and
      susceptible RMN sheep highlighted in a previous microarray experiment were
      investigated. We found an induction of Th-2 related cytokine genes expression in
      the abomasal mucosa of R sheep. Down-regulation of the PAPP-A2 gene expression
      was observed between naive and challenged sheep although no differential
      expression was recorded between challenged R and N sheep. The genotyping of this
      limited region should contribute to the ability to predict the intrinsic
      resistance level of sheep.

PMID- 24939585
TI  - Genome-wide association analysis demonstrates the highly polygenic character of
      age-related hearing impairment.
AB  - We performed a genome-wide association study (GWAS) to identify the genes
      responsible for age-related hearing impairment (ARHI), the most common form of
      hearing impairment in the elderly. Analysis of common variants, with and without
      adjustment for stratification and environmental covariates, rare variants and
      interactions, as well as gene-set enrichment analysis, showed no variants with
      genome-wide significance. No evidence for replication of any previously reported
      genes was found. A study of the genetic architecture indicates for the first time
      that ARHI is highly polygenic in nature, with probably no major genes involved.
      The phenotype depends on the aggregated effect of a large number of SNPs, of
      which the individual effects are undetectable in a modestly powered GWAS. We
      estimated that 22% of the variance in our data set can be explained by the
      collective effect of all genotyped SNPs. A score analysis showed a modest
      enrichment in causative SNPs among the SNPs with a P-value below 0.01. 

PMID- 24939586
TI  - Heterozygous germline mutations in A2ML1 are associated with a disorder
      clinically related to Noonan syndrome.
AB  - Noonan syndrome (NS) is a developmental disorder characterized by short stature,
      facial dysmorphisms and congenital heart defects. To date, all mutations known to
      cause NS are dominant, activating mutations in signal transducers of the
      RAS/mitogen-activated protein kinase (MAPK) pathway. In 25% of cases, however,
      the genetic cause of NS remains elusive, suggesting that factors other than those
      involved in the canonical RAS/MAPK pathway may also have a role. Here, we used
      family-based whole exome sequencing of a case-parent trio and identified a de
      novo mutation, p.(Arg802His), in A2ML1, which encodes the secreted protease
      inhibitor alpha-2-macroglobulin (A2M)-like-1. Subsequent resequencing of A2ML1 in
      155 cases with a clinical diagnosis of NS led to the identification of additional
      mutations in two families, p.(Arg802Leu) and p.(Arg592Leu). Functional
      characterization of these human A2ML1 mutations in zebrafish showed NS-like
      developmental defects, including a broad head, blunted face and cardiac
      malformations. Using the crystal structure of A2M, which is highly homologous to
      A2ML1, we identified the intramolecular interaction partner of p.Arg802. Mutation
      of this residue, p.Glu906, induced similar developmental defects in zebrafish,
      strengthening our conclusion that mutations in A2ML1 cause a disorder clinically
      related to NS. This is the first report of the involvement of an extracellular
      factor in a disorder clinically related to RASopathies, providing potential new
      leads for better understanding of the molecular basis of this family of
      developmental diseases. 

PMID- 24939587
TI  - Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary
      malformation syndrome (MCAP)--pure coincidence?
AB  - Megalencephaly-capillary malformation (MCAP) syndrome is an overgrowth syndrome
      that is diagnosed by clinical criteria. Recently, somatic and germline variants
      in genes that are involved in the PI3K-AKT pathway (AKT3, PIK3R2 and PIK3CA) have
      been described to be associated with MCAP and/or other related megalencephaly
      syndromes. We performed trio-exome sequencing in a 6-year-old boy and his healthy
      parents. Clinical features were macrocephaly, cutis marmorata, angiomata,
      asymmetric overgrowth, developmental delay, discrete midline facial nevus
      flammeus, toe syndactyly and postaxial polydactyly--thus, clearly an MCAP
      phenotype. Exome sequencing revealed a pathogenic de novo germline variant in the
      PTPN11 gene (c.1529A>G; p.(Gln510Arg)), which has so far been associated with
      Noonan, as well as LEOPARD syndrome. Whole-exome sequencing (>100 * coverage) did
      not reveal any alteration in the known megalencephaly genes. However, ultra-deep
      sequencing results from saliva (>1000 * coverage) revealed a 22% mosaic variant
      in PIK3CA (c.2740G>A; p.(Gly914Arg)). To our knowledge, this report is the first
      description of a PTPN11 germline variant in an MCAP patient. Data from
      experimental studies show a complex interaction of SHP2 (gene product of PTPN11)
      and the PI3K-AKT pathway. We hypothesize that certain PTPN11 germline variants
      might drive toward additional second-hit alterations.

PMID- 24939588
TI  - Linking genotypes database with locus-specific database and genotype-phenotype
      correlation in phenylketonuria.
AB  - The wide range of metabolic phenotypes in phenylketonuria is due to a large
      number of variants causing variable impairment in phenylalanine hydroxylase
      function. A total of 834 phenylalanine hydroxylase gene variants from the locus
      specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the
      BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D
      algorithms. Obtained data was correlated with residual enzyme activity, patients'
      phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both
      databases was compiled and an interactive viewer in PAHvdb database was
      implemented for structure visualization of missense variants. We found a
      quantitative relationship between phenylalanine hydroxylase protein stability and
      enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype
      (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) =
      0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and
      enzyme activity were most powerful to predict patients' phenotype and
      tetrahydrobiopterin response. Phenotype prediction was most accurate in
      deleterious genotypes (~ 100%), followed by homozygous (92.9%), hemizygous
      (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin
      response was correctly predicted in 71.0% of all cases. To our knowledge this is
      the largest study using algorithms for the prediction of patients' phenotype and
      tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from
      the locus-specific and genotypes database.

PMID- 24939589
TI  - Improving accuracy of rare variant imputation with a two-step imputation
      approach.
AB  - Genotype imputation has been the pillar of the success of genome-wide association
      studies (GWAS) for identifying common variants associated with common diseases.
      However, most GWAS have been run using only 60 HapMap samples as reference for
      imputation, meaning less frequent and rare variants not being comprehensively
      scrutinized. Next-generation arrays ensuring sufficient coverage together with
      new reference panels, as the 1000 Genomes panel, are emerging to facilitate
      imputation of low frequent single-nucleotide polymorphisms (minor allele
      frequency (MAF) <5%). In this study, we present a two-step imputation approach
      improving the quality of the 1000 Genomes imputation by genotyping only a subset
      of samples to create a local reference population on a dense array with many low
      frequency markers. In this approach, the study sample, genotyped with a first
      generation array, is imputed first to the local reference sample genotyped on a
      dense array and hereafter to the 1000 Genomes reference panel. We show that mean
      imputation quality, measured by the r(2) using this approach, increases by 28%
      for variants with a MAF between 1 and 5% as compared with direct imputation to
      1000 Genomes reference. Similarly, the concordance rate between calls of imputed
      and true genotypes was found to be significantly higher for heterozygotes (P<1e
      15) and rare homozygote calls (P<1e-15) in this low frequency range. The two-step
      approach in our setting improves imputation quality compared with traditional
      direct imputation noteworthy in the low-frequency spectrum and is a cost
      effective strategy in large epidemiological studies. 

PMID- 24939591
TI  - Production of anti TNF-alpha antibodies in eukaryotic cells using different
      combinations of vectors carrying heavy and light chains.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a key role in rheumatoid arthritis
      and some other autoimmune diseases. Therapy with anti-TNF-alpha recombinant
      antibodies (Ab) appears to be highly effective. Production of new hyper-producing
      eukaryotic cell lines can decrease the treatment cost, which currently is very
      high. However, due to the complexity of protein transcription, translation,
      processing, and secretion in mammalian cells, the stages at which antibody
      expression is affected are still poorly determined. The aim of this work was to
      compare the productivity of two cell lines developed in CHO DG44 cells, deficient
      in dihydrofolate reductase, transfected with vectors carrying either heavy (H) or
      light (L) chains of chimeric antibody under different combinations of selective
      elements. Both H and L chains were cloned either in pOptiVEC or pcDNA3.3 vectors
      and different combinations were used to produce HL and LH cell lines. We have
      shown that Ab production has been low and comparable between HL and LH cells
      until selection on methotrexate (MTX) when LH but not HL cells have responded
      with 3.5 times increased productivity. Flow cytometry analysis has demonstrated
      that intracellular concentration of full size Abs in LH cells was 5.6 times
      higher than in HL ones due to higher amount of H chain synthesis. No differences
      in viability between HL and LH cells have been found. We have concluded that the
      expression of H chain in the pOptiVEC vector, which is responsible for MTX
      resistance, has led to the suppression of H chain synthesis and limitation in
      full Ab assembly. 

PMID- 24939590
TI  - Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis.
AB  - We used exome sequencing to study a non-consanguineous family with two children
      who had anterior segment dysgenesis, sclerocornea, microphthalmia, hypotonia and
      developmental delays. Sanger sequencing verified two Peroxidasin (PXDN) mutations
      in both sibs--a maternally inherited, nonsense mutation, c.1021C>T predicting
      p.(Arg341*), and a paternally inherited, 23-basepair deletion causing a
      frameshift and premature protein truncation, c.2375_2397del23, predicting
      p.(Leu792Hisfs*67). We re-examined exome data from 20 other patients with
      structural eye defects and identified two additional PXDN mutations in a sporadic
      male with bilateral microphthalmia, cataracts and anterior segment dysgenesis--a
      maternally inherited, frameshift mutation, c.1192delT, predicting
      p.(Tyr398Thrfs*40) and a paternally inherited, missense substitution that was
      predicted to be deleterious, c.947 A>C, predicting p.(Gln316Pro). Mutations in
      PXDN were previously reported in three families with congenital cataracts,
      microcornea, sclerocornea and developmental glaucoma. The gene is expressed in
      corneal epithelium and is secreted into the extracellular matrix. Defective
      peroxidasin has been shown to impair sulfilimine bond formation in collagen IV, a
      constituent of the basement membrane, implying that the eye defects result
      because of loss of basement membrane integrity in the developing eye. Our finding
      of a broader phenotype than previously appreciated for PXDN mutations is typical
      for exome-sequencing studies, which have proven to be highly effective for
      mutation detection in patients with atypical presentations. We conclude that PXDN
      sequencing should be considered in microphthalmia with anterior segment
      dysgenesis.

PMID- 24939592
TI  - Salmonella phages isolated from dairy farms in Thailand show wider host range
      than a comparable set of phages isolated from U.S. dairy farms.
AB  - Salmonella is a zoonotic pathogen with globally distributed serovars as well as
      serovars predominantly found in certain regions; for example, serovar Weltevreden
      is rarely isolated in the U.S., but is common in Thailand. Relative to our
      understanding of Salmonella diversity, our understanding of the global diversity
      of Salmonella phages is limited. We hypothesized that the serovar diversity in a
      given environment and farming system will affect the Salmonella phage diversity
      associated with animal hosts. We thus isolated and characterized Salmonella
      phages from 15 small-scale dairy farms in Thailand and compared the host ranges
      of the 62 Salmonella phage isolates obtained with host range diversity for 129
      phage isolates obtained from dairy farms in the U.S. The 62 phage isolates from
      Thailand represented genome sizes ranging from 40 to 200 kb and showed lysis of 6
      25 of the 26 host strains tested (mean number of strain lysed=19). By comparison,
      phage isolates previously obtained in a survey of 15 U.S. dairy farms showed a
      narrow host range (lysis of 1-17; mean number of strains lysed=4); principal
      coordinate analysis also confirmed U.S. and Thai phages had distinct host lysis
      profiles. Our data indicate that dairy farms that differ in management practices
      and are located on different continents can yield phage isolates that differ in
      their host ranges, providing an avenue for isolation of phages with desirable
      host range characteristics for commercial applications. Farming systems
      characterized by coexistence of different animals may facilitate presence of
      Salmonella phages with wide host ranges.

PMID- 24939593
TI  - Activation of extrinsic- and Daxx-mediated pathways in lymphoid tissue of PRRSV
      infected pigs.
AB  - Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a major infectious
      pathogen in pigs leading to huge economical losses worldwide. PRRSV is able to
      escape from host immunity and causes transient infections. In the present study,
      expression of different apoptotic markers and its connection with PRRSV were
      assessed in tonsil and mediastinal lymph node from PRRSV-infected pigs. Cleaved
      caspase (CCasp)8, CCasp9, Fas, Daxx, CCasp3 and PRRSV expression were analyzed by
      immunohistochemistry. An up-regulation of CCasp8, Fas and CCasp3 expression in
      lymphocytes and macrophages from both organs was found during PRRSV infection,
      indicating the activation of the extrinsic-mediated pathway of apoptosis.
      Moreover, Daxx expression was also enhanced in macrophages of both organs,
      suggesting a simultaneous caspase-independent pathway of apoptosis. A correlation
      between the expression of the different apoptotic markers and IL-10, IL-6 and TGF
      beta but not with PRRSV antigen was found in our study, which supports the
      hypothesis of an indirect mechanism in PRRSV-induced apoptosis. 

PMID- 24939594
TI  - A longitudinal assessment of early childhood education with integrated speech
      therapy for children with significant language impairment in Germany.
AB  - BACKGROUND: In Lower Saxony, Germany, pre-school children with language- and
      speech-deficits have the opportunity to access kindergartens with integrated
      language-/speech therapy prior to attending primary school, both regular or with
      integrated speech therapy. It is unknown whether these early childhood education
      treatments are helpful and effective. AIMS: To determine the value of early
      language-/speech therapy treatment in combination with support of personality
      traits during the pre-school and primary school period on the long-term social
      and academic development of children with significant language-/speech delay.
      METHODS & PROCEDURES: We conducted prospective longitudinal case series,
      following the academic progress of 71 children after they had been discharged
      from a speech therapy kindergarten (STK) up to 19 years previously. Data
      collection included details on language/speech impairment, socio-economic
      factors, psycho-social skills and intelligence quotient. RESULTS & IMPLICATIONS:
      At the end of the follow-up period, 58 children were attending secondary schools:
      44 (76%) children attended a regular secondary school, whereas 14 (24%) children
      were enrolled in a school with special needs education. The results suggest that
      self-awareness and intelligence quotient in this study cohort correlated with
      later academic achievements. CONCLUSION & IMPLICATIONS: Kindergartens and primary
      schools which support curriculum-integrated language-/speech therapy and allow
      for different personality traits appear to improve longterm development and
      academic outcome of children with language-/speech impairment or delay.

PMID- 24939597
TI  - Prognostic factors for postoperative morbidity and tumour response after
      neoadjuvant chemoradiation followed by resection for rectal cancer.
AB  - BACKGROUND AND PURPOSE: In patients with locally advanced rectal cancer treated
      with neoadjuvant chemoradiation followed by rectal resection, postoperative
      morbidity is a significant clinical problem. Pathologic complete tumour response
      seems to give the best prognosis in the long term. Little is known about the
      factors that are associated with postoperative complications and pathologic
      complete response. The aim of this retrospective study was to identify and
      describe these factors. METHODS: Ninety-nine consecutive patients with locally
      advanced rectal cancer who underwent neoadjuvant chemoradiation (50 Gy and
      capecitabine) followed by surgery at our institute between January 2007 and May
      2012 were identified. Postoperative complications were graded according to the
      Clavien-Dindo classification. Pathologic tumour response was categorized as
      complete response or no/partial response. RESULTS: Postoperative complications
      occurred in 68 patients (69%) and grade 3-5 complications in 25 patients (25%).
      The 30-day and 90-day mortality were 1% (n = 1) and 2% (n = 2), respectively. A
      young age (p = 0.021) and a preoperative or postoperative blood transfusion (p =
      0.015) independently predicted complications. Intraoperative or postoperative
      blood transfusion (p = 0.007) and ypT0-1 stage (p = 0.037) were independent
      predictors for grade 3-5 complications. Complete response rate was 22% (n = 22);
      4% (n = 4) of patients showed no response. No independent factors predicting
      complete response were found. CONCLUSIONS: Neoadjuvant chemoradiation followed by
      rectal resection is associated with significant postoperative morbidity but
      minimal postoperative mortality. A complete response rate of 22% was achieved.

PMID- 24939599
TI  - Sensory attributes of soft drinks and their influence on consumers' preferences.
AB  - Soft drinks are beverages composed of water and other ingredients that provide
      specific sensorial attributes. Soft drink consumption patterns have recently been
      changed partially influenced by an increased availability of different types of
      beverages during the last few years. Consumers' preferences to choose one drink
      over another are influenced, not only by genetic, psychological and environmental
      factors, but also by the beverage's specific attributes. In fact, beverage
      consumption is driven by the sensations it gives. Because the main component of
      soft drinks is water, an increase in the intake of soft drinks might improve
      fluid intake and the levels of water in the body if it is regarded as an
      "essential nutrient". 

PMID- 24939598
TI  - Laparoscopic spleen-preserving distal pancreatectomy: the technique must suit the
      lesion.
AB  - Splenic preservation is currently recommended during minimally invasive surgery
      for benign tumors of the distal pancreas. The aim of this study was to evaluate
      the outcomes of patients undergoing laparoscopic spleen-preserving distal
      pancreatectomy, with particular attention paid to the technique used for spleen
      preservation (splenic vessel ligation vs preservation). A review of consecutive
      patients who underwent laparoscopic distal pancreatectomy with the intention of
      splenic preservation was conducted. Patient demographics, operative data, and
      outcomes were collected and analyzed. Fifty-five consecutive patients underwent
      laparoscopic distal pancreatectomy with the intention of splenic preservation; 5
      required splenectomy (9 %). Of the remaining 50 patients, 31 (62 %) had splenic
      vessel ligation, and 19 (38 %) had vessel preservation. Patient demographics and
      tumor size were similar. The vessel ligation group had significantly more
      pancreas removed (95 vs 52 mm, P < 0.001) and longer operative times (256 vs 201
      min, P = 0.008). Postoperative outcomes, complication rates, and splenic
      viability were similar between groups. Laparoscopic spleen-preserving distal
      pancreatectomy is a safe operation with a high rate of success (91 %). Vessel
      ligation was the chosen technical strategy for lesions that required resection of
      a greater length of pancreas. We found no advantage to either technique with
      respect to outcomes and splenic preservation. Operative approach should reflect
      technical considerations including location in the pancreas.

PMID- 24939601
TI  - To the editor. Re: Pesticides in blood from spectacled caiman (Caiman crocodilus)
      downstream of banana plantations in Costa Rica.

PMID- 24939595
TI  - Interaction between ingested nutrients and gut endocrine cells in patients with
      irritable bowel syndrome (review).
AB  - Several endocrine cell abnormalities have been reported in different segments of
      the gastrointestinal tract of patients with irritable bowel syndrome (IBS). These
      cells have specialized microvilli that project into the lumen; they function as
      sensors for the gut contents and respond to luminal stimuli (mostly ingested
      nutrients) by releasing hormones into the lamina propria, where they exert their
      effects via a paracrine/endocrine mode of action. Certain food items trigger the
      symptoms experienced by IBS patients, including those rich in fermentable oligo-,
      di- and monosaccharides, and polyols (FODMAPs). In this review, we present the
      argument that the effects of both FODMAPs and the proportional intake of
      proteins, fats and carbohydrates on IBS symptoms may be caused by an interaction
      with the gut endocrine cells. Since the gut hormones control and regulate
      gastrointestinal motility and sensation, this interaction may be responsible for
      abnormal gastrointestinal motility and the visceral hypersensitivity observed in
      these patients. There is no consistent evidence that IBS patients suffer from
      food allergy. The role of gluten intolerance in the development of IBS symptoms
      in these patients remains a matter of controversy. Individual guidance on food
      management, which includes restrictions in the intake of FODMAP-rich foods and
      testing diets with different proportions of proteins, fats and carbohydrates has
      been found to reduce the symptoms, improve the quality of life, and make the
      habitual diet of IBS patients more healthy.

PMID- 24939602
TI  - To the editor. Re: Pesticides in blood from spectacled caiman (Caiman crocodilus)
      downstream of banana plantations in Costa Rica.

PMID- 24939603
TI  - The authors' reply.

PMID- 24939604
TI  - Ecological models in ecotoxicology and ecological risk assessment: an
      introduction to the special section.

PMID- 24939605
TI  - Equations for depth of penetration of projectiles.

PMID- 24939606
TI  - Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in
      streptozotocin-induced diabetic rats.
AB  - Chronic hyperglycemia in diabetes is associated with profound changes in lipid
      and lipoprotein metabolism, with resultant alterations in particle distribution
      within lipoprotein classes. In the present study, an attempt has been made to
      explore the antihyperlipidemic effect of fisetin in streptozotocin-induced
      experimental diabetes in rats. Upon fisetin treatment to diabetic rats, the
      levels of blood glucose were significantly reduced with an improvement in plasma
      insulin. The increased levels of lipid contents in serum, hepatic, and renal
      tissues observed in diabetic rats were normalized upon fisetin administration.
      Also, the decreased levels of high-density lipoprotein cholesterol, and increased
      levels of low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol in serum
      of diabetic rats were normalized. Oil Red O staining established a large number
      of intracellular lipid droplets accumulation in the diabetic rats. Fisetin
      treatment exacerbated the degree of lipid accumulation. The results of the
      present study exemplify the antihyperlipidemic property of the fisetin. 

PMID- 24939607
TI  - Gellan sulfate core platinum coil with tenascin-C promotes intra-aneurysmal
      organization in rats.
AB  - The aims of this study were to develop a new coil, gellan sulfate core platinum
      coil (GSCC), that delivers tenascin-C (TNC) to an aneurysm (GSCC-TNC) and to
      evaluate the effects on intra-aneurysmal organization. We performed in vitro
      adsorption tests of TNC to gellan sulfate (GS). GSCC-TNC was produced by
      immersing GSCC in TNC solution under the following conditions (TNC concentration
      10, 50, or 100 MUg/mL; TNC immersion time 15, 30, or 60 min) by monitoring intra
      aneurysmal organization in a rat blind-ended aneurysm model. In addition, 20 rats
      randomly underwent implantation of a platinum coil or the GSCC-TNC produced under
      optimum conditions into an aneurysm, whose organization effects were compared in
      a blind fashion at 2 weeks post-surgery. GS demonstrated a high affinity to TNC
      in a dose-dependent fashion (affinity constant = 1.79 * 10(10) (M(-1))). GSCC
      immersed in 10 MUg/mL of TNC solution for 30 and 60 min induced similar and
      better organization of aneurysmal cavity compared with that for 15 min (the ratio
      of the organized areas in an aneurysmal cavity-15 min, 27.2 +/- 11.8 %; 30 min,
      75.6 +/- 11.9 %; 60 min, 82.6 +/- 19.7 %, respectively) with the preservation of
      the aneurysmal wall structure, while higher TNC concentrations caused the
      destruction of the aneurysmal wall. GSCC-TNC produced under 10 MUg/mL of TNC
      solution for 30 min showed a significantly better organization of aneurysms
      compared with bare platinum coils in rats. A newly developed coil, GSCC-TNC, may
      be effective for improving intra-aneurysmal organization after coil embolization.

PMID- 24939608
TI  - Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new
      cases and further evidence of heterogeneity.

PMID- 24939609
TI  - Decreased D2-40 immunoreactivity in stored paraffin sections and methods for
      preserving it.
AB  - D2-40, a monoclonal antibody against podoplanin, is a selective marker of
      lymphatic endothelium and is widely used for research on and diagnosis of
      pathology of lymphatic vessels. We examined the relation between the duration of
      tissue section storage and changes in immunostaining by D2-40 antibody; we
      evaluated also the effects of preservation methods on changes in immunostaining
      during storage. Staining by D2-40 was attenuated by long-term preservation of
      scalp skin and lymph node sections at room temperature. The attenuation of D2-40
      staining in stored sections was improved by preservation at low temperature,
      i.e., 4 degrees  or - 30 degrees  C. We investigated also the immunostaining of
      preserved tissue sections using NZ-1 and Lyve-1, which are antibodies against
      lymphatic endothelium markers. Staining by NZ-1 or Lyve-1 antibody was detected
      clearly in sections that had been stored for 16 weeks. Our study suggests that
      either long-term storage of D2-40 immunostained tissue sections should be avoided
      or the section should be preserved at low temperature.

PMID- 24939610
TI  - Incremental and comparative health care expenditures for head and neck cancer in
      the United States.
AB  - OBJECTIVES/HYPOTHESIS: Determine the incremental costs associated with head and
      neck cancer (HNCa) and compare the costs with other common cancers. STUDY DESIGN:
      Cross-sectional analysis of a healthcare expenditure database. METHODS: The
      Medical Expenditure Panel Survey is a national survey of US households. All cases
      of HNCa were extracted for 2006, 2008, and 2010. The incremental expenditures
      associated with HNCa were determined by comparing the healthcare expenditures of
      individuals with HNCa to the population without cancer, controlling for age, sex,
      education, insurance status, marital status, geographic region, and
      comorbidities. Healthcare expenditures for HNCa were then compared to individuals
      with lung cancer and colon cancer to determine relative healthcare expenditures.
      RESULTS: An estimated 264,713 patients (annualized) with HNCa were identified.
      The mean annual healthcare expenditures per individual for HNCa were $23,408 +/-
      $3,397 versus $3,860 +/- $52 for those without cancer. The mean adjusted
      incremental cost associated with HNCa was $15,852 +/- $3,297 per individual (P <
      .001). Within this incremental cost, there was an increased incremental
      outpatient services cost of $3,495 +/- $1,044 (P = .001) and an increased
      incremental hospital inpatient cost of $6,783 +/- $2,894 (P = .020) associated
      with HNCa. The annual healthcare expenditures per individual fell in between
      those for lung cancer ($25,267 +/- $2,375, P = .607) and colon cancer ($16,975 +/
      $1,291, P = .055). CONCLUSIONS: Despite its lower relative incidence, HNCa is
      associated with a significant incremental increase in annual healthcare
      expenditures per individual, which is comparable to or higher than other common
      cancers. In aggregate, the estimated annual costs associated with HNCa are $4.20
      billion.

PMID- 24939612
TI  - Sugars as bulking agents to prevent nano-crystal aggregation during spray or
      freeze-drying.
AB  - In this study, the effect of low and high molecular weight sugars on indomethacin
      nano-crystalline suspension powders prepared by spray or freeze-drying was
      evaluated. Dowfax 2A1 (negatively charged surfactant) was utilized as
      indomethacin nanosuspensions stabilizer. Dried crystalline powders with or
      without sugars were characterized for crystallinity, particle size and powder
      yield. Interactions between the nanosuspension stabilizer (i.e. Dowfax 2A1) and
      sugars were investigated by utilizing IR spectroscopy and contact angle
      measurements. The nanosuspension formulations containing small molecular weight
      sugars were non-aggregating compared to those containing polysaccharides.
      Additionally, higher powder yields were observed with formulations containing
      sugars with higher glass transition temperature during spray drying. The
      formulations containing low glass transition temperature sugars were sticking to
      the spray drier glass walls and thus resulted in lower yields. The small
      molecular weight sugars showed favorable interactions with Dowfax 2A1, as evident
      by the IR and contact angle data, possibly resulting in minimal nano-crystal
      aggregation during spray or freeze-drying. A combination of sugars (i.e. small
      molecular weight and polysaccharides) may be utilized to achieve higher spray
      drying yields and non-aggregating nano-crystalline powders. 

PMID- 24939613
TI  - Linolenic acid-modified PEG-PCL micelles for curcumin delivery.
AB  - In this study, a novel linolenic acid-modified poly(ethylene glycol)-b
      poly(epsilon-caprolactone) copolymer was prepared through radical addition, ring
      opening polymerization, and N-acylation reactions. Its structure was
      characterized by (1)H NMR and GPC. Micelles were developed by thin-film hydration
      and used as a delivery system for curcumin with high drug loading capacity of
      12.80% and entrapment efficiency of 98.53%. The water solubility of curcumin was
      increased to 2.05 mg/mL, which was approximately 1.87*10(5) times higher than
      that of free curcumin. The micelles were spherical shape with an average diameter
      of 20.8+/-0.8 nm. X-ray diffraction and FT-IR studies suggested that curcumin
      existed in the polymeric matrices under pi-pi conjugation and hydrogen bond
      interaction with the copolymer. In vitro drug release studies indicated that the
      curcumin release from linolenic acid-modified copolymer micelles met controlled
      release, and its release rate was less than that from the linolenic acid
      unmodified copolymer micelles. Cytotoxicities against Hela and A-549cells
      demonstrated that the additional pi-pi conjugation could affect curcumin's
      anticancer activity through reducing its release from micelles. Hemolysis test
      and intravenous irritation test results revealed that the linolenic acid-modified
      copolymer was safe for intravenous injection. The plasma AUC0-infinity and MRT0
      infinity of curcumin-loaded linolenic acid-conjugated poly(ethylene glycol)-b
      poly(epsilon-caprolactone) copolymer micelles were 2.75- and 3.49-fold higher
      than that of control solution, respectively. The CLz was also decreased by 2.75
      fold. So, this linolenic acid-modified copolymer might be a carrier candidate for
      curcumin delivery.

PMID- 24939611
TI  - Oncolytic polio virotherapy of cancer.
AB  - Recently, the century-old idea of targeting cancer with viruses (oncolytic
      viruses) has come of age, and promise has been documented in early stage and
      several late-stage clinical trials in a variety of cancers. Although originally
      prized for their direct tumor cytotoxicity (oncolytic virotherapy), recently, the
      proinflammatory and immunogenic effects of viral tumor infection (oncolytic
      immunotherapy) have come into focus. Indeed, a capacity for eliciting broad,
      sustained antineoplastic effects stemming from combined direct viral
      cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation,
      and recruitment of adaptive immune effector responses is the greatest asset of
      oncolytic viruses. However, it also is the source for enormous mechanistic
      complexity that must be considered for successful clinical translation. Because
      of fundamentally different relationships with their hosts (malignant or not),
      diverse replication strategies, and distinct modes of tumor cytotoxicity/killing,
      oncolytic viruses should not be referred to collectively. These agents must be
      evaluated based on their individual merits. In this review, the authors highlight
      key mechanistic principles of cancer treatment with the polio:rhinovirus chimera
      PVSRIPO and their implications for oncolytic immunotherapy in the clinic.

PMID- 24939614
TI  - The effects of material attributes on capsule fill weight and weight variability
      in dosator nozzle machines.
AB  - The goal of this work is to identify and understand the complex relationship
      between the material attributes, capsule fill weight and weight variability of
      capsules filled with a dosator nozzle machine. Six powders were characterized and
      filled into size-3 capsules in three volumes of dosing chambers and at two
      filling speeds. Subsequent multivariate data analysis was used to identify the
      influence of the material attributes on the capsule fill weight and weight
      variability. We observed a clear correlation between the capsule fill weight and
      the particle size, the air permeability and the compressibility. As the fill
      weight decreases, more factors affect capsule fill weight. For example, the wall
      friction angle, the tapped density, and the particle shape proved to be important
      factors. Larger fill weights were more affected by density while lower fill
      weights by flow and friction characteristics. No correlation was found between
      the material attributes and the weight variability. Rather, we could also see the
      major effect of process parameters on capsule fill weight and weight variability.

PMID- 24939615
TI  - Antioxidant-photosensitizer dual-loaded polymeric micelles with controllable
      production of reactive oxygen species.
AB  - Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded
      with both pheophorbide a (PhA) as a photosensitizer and beta-carotene (CAR) as a
      singlet oxygen ((1)O2) scavenger were designed to control photodynamic therapy
      (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly
      diminished PhA-generated (1)O2 through direct (1)O2 scavenging, whereas the CAR
      molecules lost their (1)O2 scavenging activity when the PhA and CAR were
      spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell
      culture systems, light irradiation at a post-treatment time that corresponded to
      the presence of the micelles in the blood environment induced negligible
      phototoxicity, whereas light irradiation at a post-treatment time that
      corresponded to the presence of the micelles in the intracellular environment
      induced remarkable phototoxicity. In addition, a longer post-treatment time
      induced greater internalization of PhA/CAR micelles, which resulted in higher
      phototoxicity, suggesting an increase in photo killing activity against the tumor
      cells of interest. Thus, the co-loading of a (1)O2 generator and a (1)O2
      scavenger into a single micelle is a potential strategy that may be useful in
      facilitating more accurate and reliable PDT with site-specific controllable
      production of singlet oxygen species for cancer treatment. 

PMID- 24939616
TI  - Evaluation of synergistic effect of biodegradable polymeric nanoparticles and
      aluminum based adjuvant for improving vaccine efficacy.
AB  - Aluminum based adjuvants have been used widely to induce long lasting protective
      immunity through vaccination. But reported incidences of toxicity and side
      effects of aluminum have raised concerns regarding their safety in childhood
      vaccines. The present study demonstrates the synergistic effect of admixture of
      polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles
      (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid
      (TT) as a model antigen. The immunological activity of the admixture formulation
      was maintained up to 180 days of storage at 5  degrees C+/-3  degrees C. Percent
      adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture
      formulation as compared to 55% in conventional vaccine. Admixture preparation
      (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival
      respectively, even at 180 days as compared to 30% survival observed in the
      conventional tetanus vaccine. The present study established the feasibility to
      formulate a dosage form with improved efficacy and reduced aluminum concentration
      for vaccination.

PMID- 24939619
TI  - Iron silicates, iron-modulated zeolite catalysts, and molecular models thereof.
AB  - Iron centres incorporated in silicate frameworks or located in their pores have
      been shown to possess unique catalytic properties. As compared to
      aluminosilicates this area of zeolite chemistry is much younger and in the first
      part of this review the findings made so far are summarised. Molecular model
      compounds may help to understand the formation, corrosion and reactivity of such
      materials or to even develop new ones. Hence, the subsequent parts deal with
      molecular iron siloxides, the number of which is still quite limited, and their
      behaviour also in relation to the iron-modified zeolites is outlined. At first,
      compounds based on an incompletely condensed cubic silsequioxane are discussed,
      before iron(III) complexes of more basic siloxide ligands with varying steric
      demands are described. Finally, recent developments based on branched polydentate
      siloxides are presented. 

PMID- 24939618
TI  - Targeted in vivo photodynamic therapy with epidermal growth factor receptor
      specific peptide linked nanoparticles.
AB  - In targeted photodynamic therapy (tPDT), photosensitizers (PS) are targeted to
      disease tissue to reduce the dosage of PS and in addition to reduce the photo
      damage to the non-target tissue. We synthesized iron oxide nanoparticles (NP)
      armored with tumor targeting peptide and PS for targeted PDT. Chitosan covered
      Fe3O4 NPs (30 nm) were deposited with gold NPs to generate two distinct chemical
      surfaces. To the gold particles PS was attached with a lipoic acid linker. Human
      epidermal growth factor receptor (hEGFR)-specific peptide was also attached to
      the same particles via a nickel-nitrilotriacetic acid linker attached to the
      chitosan. Using these nanoparticles, peptide specific uptake and PDT mediated
      cell death of the SK-OV-3 cells (Her2(+) positive cells) were demonstrated by
      confocal microscopy, T2 imaging and viability assays. Peptide mediated
      preferential distribution of these NPs into tumor tissue was also shown in a
      xenograft tumor model. After one intravenous injection and one PDT dose, peptide
      bound NPs retarded tumor growth significantly compared to dark controls or
      treatments with NPs without peptide. The tumor retardation by targeted NPs was
      achieved at a PS concentration of 3.9 nmol/animal, whereas similar effect was
      seen with free PS at 220 nmol/animal. Therapeutic potential of these peptide
      containing NPs would be a useful in targeted PDT and in imaging the target
      tissue.

PMID- 24939617
TI  - Characterization of different vitamin E carriers intended for pulmonary drug
      delivery.
AB  - The targeted release of drugs intended for pulmonary delivery is a research field
      which has been so far rather unexploited but is currently becoming increasingly
      attractive. Liquid dispersions encapsulating vitamin E (liposomes, micelles, nano
      emulsion, and solid lipid particles) were prepared using various methods based on
      membrane contactor. The dispersions were nebulized and aerodynamic
      characteristics of the generated aerosols were assessed using two different
      methods: laser light scattering and cascade impaction. When the laser diffraction
      technique was used, results showed that fine particle fractions (<5 MUm) were 19,
      29, 38 and 71% for solid lipid particles, micelles, nano-emulsion and liposomes,
      respectively. When the impaction method was applied, using a next generation
      pharmaceutical impactor operated at 30 l/min, results showed that fine particle
      fractions were 39, 78, 82 and 87% for solid lipid particles, micelles, nano
      emulsion and liposomes, respectively. The differences observed between the
      results obtained from both methods confirm that the laser diffraction method is
      not always suitable for aerodynamic characterization of aerosols and should be
      validated against an impaction method. Nebulization of the drug-carrier systems
      led to an increase of their size most likely due to aggregation phenomena. The
      size was increased by a factor of 2-26 depending on the encapsulation system. The
      most important aggregation was obtained with nano-emulsion; the less one with
      solid lipid particles. The mass median aerodynamic diameter (MMAD) of the
      generated aerosols ranged from 1.76 to 6.10 MUm. The application of a
      mathematical model, the Multiple-Path Particle Dosimetry (MPPD), for the
      prediction of the pulmonary deposit gave encouraging results. The rate of vitamin
      E able to reach the lung ranged from 37.6 (for the liposomes) to 51.6% (for the
      micelles). The obtained results showed that the different systems developed for
      vitamin E encapsulation were suitable to target the lung after pulmonary
      administration by nebulization.

PMID- 24939620
TI  - Dimorphic fungal osteoarticular infections.
AB  - The objective of this investigation was to review the clinical manifestations,
      management, and outcome of osteoarticular infections caused by dimorphic fungi.
      We exhaustively reviewed reports of bone and joint infections caused by dimorphic
      fungi published between 1970 and 2012. Underlying conditions, microbiological
      features, histological characteristics, clinical manifestations, antifungal
      therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases
      (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing
      condition. Histopathology performed in 128 (57 %) cases and culture in 170
      confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was
      obtained from an extra-osteoarticular site in 16 cases. The median diagnostic
      time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent
      pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces
      dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides
      brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in
      87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral
      osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic
      antifungal agents were used in 216 (97 %) patients and in combination with
      surgery in 129 (60 %). Following the Infectious Diseases Society of America
      (IDSA) guidelines, a successful initial medical strategy was observed in 97/116
      (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P.
      marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular
      infections have distinctive clinical presentations, occur predominantly in
      apparently immunocompetent patients, develop often during disseminated disease,
      and may require surgical intervention.

PMID- 24939621
TI  - AdeRS combination codes differentiate the response to efflux pump inhibitors in
      tigecycline-resistant isolates of extensively drug-resistant Acinetobacter
      baumannii.
AB  - Tigecycline (TGC)-resistant extensively drug-resistant Acinetobacter baumannii
      (XDRAB) is an increasing threat in regard to nosocomial infections. The
      resistance-nodulation-cell division (RND) efflux pump has played an important
      role in TGC resistance. In this study, total 81 TGC-resistant XDRAB isolates were
      analyzed for their responses to the efflux pump inhibitor 1-(1-naphthylmethyl)
      piperazine (NMP). We found that NMP could reduce by 4-fold or greater than 4-fold
      the minimum inhibitory concentration (MIC) of TGC in 45 isolates (55.6 %). After
      typing with pulsed-field gel electrophoresis (PFGE), group A appeared to be the
      major cluster with good synergistic response to NMP. Transcripts of the AdeABC
      efflux pump gene were consistently more correlated with TGC resistance than
      transcripts of the AdeFGJ or AdeIJK efflux pump genes in these isolates. Of the
      81 isolates, the amino acid sequences of AdeR and AdeS were further classified
      and combined into 31 different codes. Although the dissemination of TGC-resistant
      XDRAB isolates was genetically diverse in our hospital, their responses to NMP
      conversion were still strain-dependent. We found that AdeRS combination codes
      were better than PFGE typing in separating groups of isolates with different
      sensitivity to NMP conversion.

PMID- 24939622
TI  - Acetylation regulates the stability of glutamate carboxypeptidase II protein in
      human astrocytes.
AB  - Glutamate carboxypeptidase II (GCPII) is known to be implicated in brain diseases
      such as schizophrenia and bipolar disorder, and dramatically increases in
      prostate cancer. Here, we investigated the regulation of GCPII expression in
      astrocytes and examined whether GCPII is epigenetically regulated through histone
      modification. In this study, valproic acid (VPA), a drug used for bipolar
      disorder and epilepsy and a known histone deacetylase (HDAC) inhibitor was used.
      We found that acute exposure of VPA for 4-6h increased the GCPII protein level in
      human astrocyte U87MG cells but did not have a similar effect after 12-24h
      exposure. Real-time polymerase chain reaction analysis revealed that VPA did not
      affect the GCPII mRNA expression. In contrast, decrease in GCPII protein level by
      cycloheximide treatment was blocked by VPA, indicating that VPA increases GCPII
      protein stability. Treatment with MG132, a proteasome inhibitor, suggested that
      the VPA-induced increase of GCPII protein level is dependent on the
      ubiquitin/proteasome pathway. In addition, immunoprecipitation analysis revealed
      that VPA increased the acetylation of GCPII protein at the lysine residues and
      facilitated a decrease of the poly-ubiquitinated GCPII level. Similarly, M344, a
      specific HDAC 1/6 inhibitor, also increased the GCPII protein level. In contrast,
      treatment with C646, a histone acetyltransferase inhibitor of p300/CBP,
      significantly reduced the level of GCPII protein. Taken together, this study
      demonstrated that the increase in GCPII induced by VPA is not due to the
      classical epigenetic mechanism, but via enhanced acetylation of lysine residues
      in GCPII. 

PMID- 24939623
TI  - Predictors of hemodynamic instability during surgery for pheochromocytoma.
AB  - BACKGROUND: Resection of pheochromocytoma is often associated with hemodynamic
      instability (HDI). We examined patient and tumor factors that may influence HDI.
      The effect of pretreatment with nonselective alpha blockade phenoxybenzamine
      (PXB) versus selective alpha blockade on HDI and outcomes was also evaluated.
      METHODS: The records of 91 patients who underwent adrenalectomy between 2002 and
      2013 were retrospectively reviewed. HDI was determined by number of
      intraoperative episodes of systolic blood pressure (SBP) > 200 mmHg, those
      greater than or less than 30 % of baseline, heart rate > 110 bpm, and the need
      for postoperative vasopressors. Fishers exact, t test and regressions were
      performed. RESULTS: Among 91 patients, 78 % received PXB, 18 % selective alpha
      blockade and 4 % no adrenergic blockade. Patient demographics, tumor factors and
      surgical approach were similar among the blockade groups. On multivariate
      analysis, increasing tumor size was associated with a significant rise in the
      number of episodes of SBP > 30 % [rate ratio (RR) 1.40] and an increased
      postoperative vasopressor requirement [odds ratio (OR) 1.23]. Open adrenalectomy
      and use of selective blockade were associated with an increased number of
      episodes of SBP > 200 mmHg (RR 27.8 and RR 20.9, respectively). Open
      adrenalectomy was also associated with increased readmissions (OR 12.3),
      complications (OR 5.6), use of postoperative vasopressors (OR 4.4) and hospital
      stay (4.6 days longer). There were no differences in other HDI measurements or
      postoperative outcomes among the blockade groups. CONCLUSIONS: Tumor size, open
      adrenalectomy, and type of alpha blockade were associated with intraoperative HDI
      during pheochromocytoma resection. Selective blockade was associated with
      significantly more episodes of intraoperative hypertension but no perioperative
      adverse outcomes.

PMID- 24939624
TI  - Prognostic impact of clinicopathological features and expression of biomarkers
      related to (18)F-FDG uptake in esophageal cancer.
AB  - PURPOSE: To analyze the association between pretreatment 18-F-fluoro-deoxyglucose
      (FDG) uptake and characteristics of aggressive tumor biology in predicting
      outcome in esophageal cancer (EC). METHODS: Tumor FDG-uptake was measured by
      maximum standardized uptake values (SUVmax) in 47 patients undergoing
      esophagectomy with curative intent. ROC analyses were used to predict an optimal
      SUVmax cutoff for survival. Expression of hexokinase-II (HK-II), glucose
      transporter I (GLUT-I), hypoxia inducible factor-1alpha (HIF-Ialpha), vascular
      endothelial growth factor-C (VEGF-C), p53, and proliferative activity (Ki-67)
      were correlated with SUVmax values and clinicopathological characteristics.
      RESULTS: A SUVmax > 3.67 predicted a significantly lower disease-free survival
      (DFS) and distant recurrence-free survival (p = 0.022 and p = 0.005). High HK-II
      expression was correlated with reduced SUVmax values (p = 0.002) and was
      significantly higher in esophageal adenocarcinoma compared with squamous cell
      carcinoma (p = 0.005). Preoperative high FDG uptake in primary tumors was
      associated with nodal metastases (pN1; Spearman correlation 0.39, p = 0.01). We
      found no positive correlation between SUVmax and GLUT-1, HK-1, HIF-Ialpha 1, VEGF
      C, p53, and Ki-67 expression. CONCLUSIONS: High preoperative FDG-uptake strongly
      predicts poor survival outcome and is associated with lymph node metastases in EC
      patients. HK-II expression was related to SUVmax and DFS.

PMID- 24939625
TI  - The importance of fasting blood glucose in screening for gestational diabetes.
AB  - OBJECTIVE: To determine how well an isolated abnormal fasting blood glucose (FBG)
      value on the 1-step, 75-g, 2-hour glucose tolerance test (GTT) indicates
      significant gestational diabetes (GDM). METHODS: Retrospective cohort study,
      January 2011 to May 2012. Patients diagnosed by the 1-step method were assigned
      by their abnormal results to the isolated fasting (FBG), isolated 1-hour (1HBG),
      isolated 2-hour (2HBG), or multiple-value (>=2BG) group. Characteristics and
      outcomes were compared using ANOVA, Kruskal--Wallis, and Chi-squared tests.
      RESULTS: 324 patients were included. Compared to other groups, the FBG group (N =
      23) had the highest incidence of requiring medical therapy (78.26%), mean body
      mass index (29.40 +/- 6.20 kg/m(2)), and percentage of Black plus Hispanic women
      (60.87%). CONCLUSIONS: Seven percent of women were diagnosed with GDM by an
      isolated abnormal fasting BG and have significant disease. This group should not
      be missed; therefore, fasting BG should be integrated into all GDM screening.

PMID- 24939626
TI  - Is manual palpation of the uterine scar following vaginal birth after cesarean
      section (VBAC) helpful?
AB  - Risk of uterine rupture with trial of labor after cesarean (TOLAC) is less than
      one percent. Discovery of uterine rupture often occurs during labor. In our case,
      the uterine scar is discovered to be ruptured during the postpartum period. The
      exact cause and time of uterine rupture is difficult to ascertain in this case,
      yet manual palpation of the uterine scar did not aid in the eventual diagnosis. 

PMID- 24939627
TI  - Syngeneic transplantation of newborn splenocytes in a murine model of neonatal
      ischemia-reperfusion brain injury.
AB  - OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) is caused by brain
      injury that occurs in a developing fetus or infant. Stem cell transplantation can
      reportedly induce functional recovery in animal models of HIE. Murine neonatal
      splenocytes are enriched with immature blood stem cells and are used for the
      investigation of murine models of syngeneic transplantation. The aim of this
      study was to investigate the therapeutic potential of newborn splenocytes in a
      murine model of neonatal ischemia-reperfusion brain injury. METHODS: C57BL/6N
      mice (postnatal day 7) underwent right common carotid artery occlusion with an
      aneurysm clip. Following hypoxic exposure, reperfusion was achieved by unclamping
      the artery. Newborn splenocytes were transplanted intravenously at 3 weeks after
      injury. RESULTS: The splenocytes transplanted group tended to show an improvement
      in behavioral tests, but it was not significantly different compared with the
      control groups. The transplanted cells were localized in various organs including
      injured brain tissue over 3 weeks. In the penumbra region of the brain, vascular
      endothelial growth factor (VEGF) expression was upregulated after
      transplantation. CONCLUSIONS: These results showed that syngeneic transplantation
      of newborn splenocytes achieved the long-term survival of the grafts and exerted
      influence the microenvironment in the injured brains of mice.

PMID- 24939628
TI  - Neonatal morbidities among full-term infants born to obese mothers.
AB  - INTRODUCTION: Impact of maternal obesity on full-term neonates is not known.
      OBJECTIVE: We hypothesized increased incidence of neonatal morbidities requiring
      NICU admission in full-term neonates of obese women compared to neonates of
      normal-weight women. METHODS: Data from full-term pregnancies collected in the
      Consortium of Safe Labor study were analyzed. Maternal BMI was classified using
      the WHO criteria. Incidence of neonatal outcomes including sepsis, PDA, NEC,
      respiratory distress, or their combination were compared between newborns of
      obese and normal-weight women. RESULTS: Of the 109 488 women included in the
      study, 17.7% were obese. Maternal co-morbidities (diabetes, gestational diabetes,
      hypertension, and preeclampsia) increased with increasing maternal BMI. Both
      maternal obesity and its related co-morbidities were associated with higher
      incidence of neonatal morbidities. After adjusting for maternal comorbidities,
      there was a higher incidence of sepsis (AOR 1.91(1.45-2.50)), and combination of
      any of the neonatal outcomes (AOR 1.66(1.32-2.09)) among newborns of obese women
      than those of normal-weight women, along with an increased trend for incidence of
      PDA (Cochran-Armitage Test (CA) = 23.1, p < 0.0001) and NEC (CA = 7.2, p =
      0.007). CONCLUSION: Maternal obesity is independently associated with increased
      incidence of neonatal sepsis and a combination of neonatal morbidities in full
      term newborns with an increased trend for PDA and NEC.

PMID- 24939629
TI  - Does preeclampsia involve the pancreas? A report of original research.
AB  - OBJECTIVE: To analyze the effect, if any, of pregnancy-related hypertension on
      the pancreas. METHODS: A database of pregnant women with hyperbilirubinemia was
      reviewed for cases with serum amylase values. These cases were linked to a
      computerized obstetric database, and women were analyzed according to the
      diagnosis of preeclampsia. RESULTS: A total of 292 consecutive women with
      hyperbilirubinemia during pregnancy delivered at our institution between 2005 and
      2011. Of these, 52 (18%) were diagnosed with preeclampsia, and in only nine was
      serum amylase abnormally elevated. CONCLUSION: Using serum analytes as surrogates
      for organ injury, it appears preeclampsia infrequently affects the pancreas.

PMID- 24939630
TI  - Trans-cervical double balloon catheter with and without extra-amniotic saline
      infusion for cervical ripening: a prospective quasi-randomized trial.
AB  - OBJECTIVE: To compare the efficacy and safety of the trans-cervical double
      balloon catheter with and without extra-amniotic saline infusion (EASI) for
      cervical ripening. METHODS: This is a secondary analysis of a prospective
      randomized study conducted between November 2007 and January 2011 evaluating
      different ripening methods. Women presenting for labor induction were assigned to
      receive the double balloon catheter with (study group) or without EASI (control
      group). Outcomes included time from device insertion to delivery, cesarean
      section rates, and adverse events. RESULTS: One hundred and sixty women completed
      the study. Cesarean section rate (8.3% in study group, versus 20% in controls p =
      0.07) and ripening success were comparable between the groups. Catheter insertion
      to delivery interval was significantly shorter and spontaneous catheter expulsion
      rate was significantly higher in the study group (14:19 hours versus 20:45 hours,
      p < 0.001, and 68.5% versus 51%, p = 0.04, respectively). Hospitalization length
      was significantly shorter in the study arm. There were no differences in other
      outcomes evaluated. A multivariable analysis found the EASI to be an independent
      predictor of a shorter insertion to delivery interval. CONCLUSIONS: The addition
      of EASI to the double balloon catheter for cervical ripening results in a shorter
      labor induction process without compromising its safety.

PMID- 24939631
TI  - Evolution of coronary stents in patients with diabetes: are clinical outcomes
      still improving?
AB  - Diabetic patients are prone to diffuse and accelerated atherosclerosis, which
      increases the likelihood of requiring myocardial revascularization. Diabetes
      mellitus is a strong risk factor for restenosis following coronary stenting, with
      greater need for repeat revascularization and inferior clinical outcomes. Despite
      the recent advances in drug-eluting stent technology, diabetic patients are still
      at higher risk of adverse clinical events after coronary angioplasty. The focus
      of this review is to describe the evolution of the percutaneous management of
      diabetic patients with coronary artery disease and to define if any real progress
      has been made in terms of safety and efficacy with the use of the second
      generation drug-eluting stents in this high-risk population. 

PMID- 24939632
TI  - Incidence and Management of Rash in Telaprevir-Treated Patients.
AB  - BACKGROUND: Telaprevir-induced rash is a common, therapy-limiting adverse drug
      event (ADE) for patients with hepatitis c virus (HCV) infection. Given the
      similarity between telaprevir and simeprevir, real-world management of rash
      during treatment with an NS3/4A protease inhibitor and its implications are
      important. OBJECTIVE: The objectives of this study were to determine the
      incidence of rash in telaprevir-treated patients, its management, and the impact
      on sustained virological response and to identify any risk factors for rash
      development. METHOD: This was a retrospective study of adult patients who were
      treated with telaprevir in a hepatology clinic from July 1, 2011, to August 31,
      2012. Pertinent information on demographics, past medical history, medications,
      laboratory data, outcomes of rash, other ADEs related to treatment, and physician
      grading of rash were collected. RESULT: Of 159 patients included, 44% (70/159)
      developed rash, and 4% (7/159) discontinued therapy because of rash. Median
      number of days until rash did not differ between patients who continued and
      discontinued therapy (25 vs 45, respectively; P = 0.88). Patients who developed
      rash were more likely to have lower actual body weight (ABW) or body mass index
      (BMI; P <= 0.01). No significant difference in rash development when drug-allergy
      history was considered was found. Most patients who continued telaprevir were
      prescribed topical corticosteroids (93.7%) and cetirizine (41.3%). Patients who
      discontinued therapy were more likely to be evaluated by dermatology (P = 0.002),
      prescribed oral corticosteroids (P = 0.02), hydroxyzine (P = 0.001), and topical
      triamcinolone (P = 0.01). CONCLUSION: ABW and BMI appear to be related to rash
      development. This finding may have implications in the treatment of HCV with
      simeprevir, given its similarity to telaprevir.

PMID- 24939633
TI  - Patient-Level Medication Regimen Complexity in Patients With HIV.
AB  - BACKGROUND: Patients with HIV often have multiple medications besides
      antiretrovirals (ARV). Medication regimen complexity-formulations, dosing
      frequencies, and additional directions-expands pill burden by considering self
      care demands. Studies show an inverse association between ARV adherence and
      medication complexity for ARVs only. Patient-level medication regimen complexity
      beyond ARV complexity is unknown. OBJECTIVE: To measure and characterize Patient
      level Medication Regimen Complexity Index (pMRCI) and Antiretroviral Medication
      Regimen Complexity Index (ARCI) for patients in 2 HIV clinics. We hypothesized
      that an all-medication complexity metric will exceed disease-state-defined
      complexity metrics; for ARVs only, the pMRCI score will be smaller than the ARCI
      score by capturing fewer features of regimens. Associations between complexity
      and adherence were not assessed. METHOD: Electronic records supplied a
      retrospective, random sample of adult patients with HIV; medication lists were
      used to code the pMRCI (n=200). A random subsample (n=66) was coded using ARCI
      for ARV regimens only. RESULT: Medication counts ranged from 1 to 27; pMRCI
      scores ranged from 2 to 67.5. ARVs contributed roughly 25% to the pMRCI; other
      prescriptions contributed about 66%. Dosing frequency made the largest
      contribution of all components (62%) to the pMRCI. For ARVs, pMRCI and ARCI
      scores did not differ statistically. CONCLUSION: Unique dosing frequencies raised
      complexity and may provide opportunities for intervention. Other prescriptions
      drove pMRCI scores, suggesting that HIV management programs should review all
      medications. A patient-level approach added value to understanding the role of
      medications in patient complexity; future work can assess association of pMRCI
      with adherence and patient outcomes.

PMID- 24939634
TI  - Fixed-Dose Rasburicase in Overweight and Obese Patients Versus Normal-Weight
      Patients.
AB  - BACKGROUND: Fixed-dose rasburicase (FDR) is common practice in treating
      hyperuricemia associated with tumor lysis syndrome in adults; however, there is a
      lack of data regarding the effectiveness of this dosing strategy specifically in
      the overweight and obese patient populations. OBJECTIVE: To determine if patient
      weight per body mass index (BMI) category is associated with failure of initial
      FDR as defined by the need for additional dose(s) based on a uric acid level
      (UAL) >=7.5 mg/dL within 10 days of previous rasburicase administration. METHOD:
      Adults who received FDR per institutional guidelines from October 2008 to August
      2013 were reviewed. Patients had either a baseline UAL >=7.5 mg/dL or were
      considered high risk (leukemia or lymphoma diagnosis with white blood cell count
      >50 000/mm3 or lactate dehydrogenase level greater than 2 times the upper limit
      of normal). Patients were stratified by BMI as underweight (<18.5), normal (18.5
      24.9), overweight (25-29.9), or obese (30+). RESULT: Overall, 12 out of 151
      patients who received FDR required a repeat dose of rasburicase. The percentage
      of patients requiring a repeat rasburicase dose was not different between
      obese/overweight versus normal/underweight patients (8.7% vs 6.4%, P = 0.75).
      Similarly, there was no difference between obese alone versus normal/underweight
      patients (12.3% vs 6.4%; P = 0.51). CONCLUSION: In this retrospective analysis,
      patient BMI did not correlate with failure of FDR in adults, suggesting that this
      dosing strategy is efficacious in the adult population.

PMID- 24939635
TI  - Fulminant Invasive Pulmonary Aspergillosis After a Near-Drowning Accident in an
      Immunocompetent Patient.
AB  - OBJECTIVE: To report on invasive aspergillosis infection in an immunocompetent
      adult after a near-drowning event, which allowed this pathogen to easily gain
      access to the human respiratory system and result in rapid, severe infection.
      CASE SUMMARY: A 51-year-old female developed severe pneumonia after a near
      drowning accident. Two days after admission, a bronchial alveolar lavage (BAL)
      was performed and was positive for Aspergillus fumigatus. After a 30-day hospital
      course, multiple antifungals, and various routes of administration, the patient
      expired. DISCUSSION:: Pneumonia is particularly common because of the aspiration
      of contaminated water. Whereas pneumococci, staphylococci, and Gram-negative
      bacteria are all common pathogens for this type of infection, fungi such as
      Aspergillus spp can also be involved and may be life threatening. Typically,
      these cases are reported in individuals with an immunodeficiency such as from
      receipt of myelosuppressive chemotherapy, bone marrow transplants, or lung
      transplants. Despite initiation of an appropriate empirical antifungal regimen,
      the rapid recovery of A fumigatus from pulmonary alveolar lavage and BAL samples
      as well as extremely elevated levels of galactomannan and (1->3)-beta-D glucan
      may have indicated an invasive fungal infection (IFI). CONCLUSION:: IFIs are
      uncommon in immunocompetent adults, but in the event of a near-drowning accident,
      environmental fungi can gain access to the human respiratory system and result in
      rapid, severe infection. Based on this case and the others described, it appears
      that near-drowning patients need an early initial evaluation for IFI.

PMID- 24939636
TI  - Catalytic intermolecular alkene oxyamination with nitrenes.
AB  - The Rh(II)-catalyzed intermolecular addition of nitrenes to aromatic and
      aliphatic alkenes provides vicinal amino alcohols with yields of up to 95 % and
      complete regioselectivity. This 1,2-oxyamination reaction involves the formation
      of an aziridine intermediate that undergoes in situ ring opening. The latter is
      induced by the Rh-bound nitrene that behaves as a Lewis acid.

PMID- 24939637
TI  - One-component revision in total hip arthroplasty: the fate of the retained
      component.
AB  - The purpose of the present study was to evaluate the long-term outcome of the
      unrevised part in one-component total hip arthroplasty revision (index
      operation). Forty-four patients (46 hips) with a mean age of 58years at the time
      of the index operation were included. At the final follow-up, 4 of the 19 (21%)
      unrevised acetabular components and 6 of the 27 (22%) unrevised femoral
      components were subsequently revised at a mean time of 14 and 11years from the
      index operation, and 22 and 24years from the primary operation, respectively. We
      concluded that revision of a stable component is not justifiable on the basis of
      its long duration in use or non-ideal position or possible loosening on
      radiographs.

PMID- 24939638
TI  - Fixation and wear with a contemporary acetabular component and cross-linked
      polyethylene at minimum 10-year follow-up.
AB  - Long term total hip arthroplasty follow-up has demonstrated bearing surface wear
      and failure of fixation as the major modes of failure. The purpose of this study
      was to evaluate the minimum 10year results of a third generation cementless
      acetabular component using moderately cross-linked polyethylene liners. 150
      primary THAs were evaluated clinically for need for revision and activity
      evaluated using accelerometers, WOMAC, Tegner and UCLA activity-level scores.
      Radiographs were evaluated for wear, osteolysis and loosening. We compared this
      cohort to three of our previously reported cohorts. The only revision was
      unrelated to liner wear and all acetabular components were bone ingrown. There
      were no cases of acetabular osteolysis and one case of femoral osteolysis.
      Average steps per year were 1.59 million. Mean steady state wear rate averaged
      0.04mm/year. At 10-years, excellent fixation and low wear were demonstrated using
      a cementless acetabular construct and moderately cross-linked polyethylene liner.
      LEVEL OF EVIDENCE: Therapeutic study, Level III (retrospective comparative study
      prospective cohort with historical control).

PMID- 24939639
TI  - Development of high drug loaded and customizing novel nanoparticles for modulated
      and controlled release of Paclitaxel.
AB  - PURPOSE: The objective of this study was to develop a custom-tailored polymeric
      drug delivery system for paclitaxel, employing a novel biodegradable block co
      polymer (P), intended to be intravenously administered, capable of improving
      therapeutic index of the drug and devoid of the adverse effect of an uncontrolled
      release. METHODS: Paclitaxel loaded nanoparticles (PTX-NPs) were prepared by a
      modified nanoprecipitation method and emulsification-solvent evaporation method.
      Our approach involves a focusing on the formulation parameters that can be
      modified in order to obtain completely customized NPs in terms of size, zeta
      potential, drug content and release profile. The biocompatibility and anti
      proliferative efficiency of PTX-NPs against glioblastoma cell line were evaluated
      in vitro by MTS. RESULTS: All formulations showed spherical nanometric (<200 nm),
      monodisperse (~0.1), Poly (Ethylene Glycol) (PEG)-coated and negatively charged
      particles. Selected NPs revealed higher PTX content (up to 24%) in comparison
      with polyester-based NPs. The release behaviour of PTX from the developed NPs
      exhibited an approximately first-order profile, without initial burst and
      characterized by a slow and constant release. Hydrophobic character of the NPs
      can be set in order to achieve a slower and more controlled release for a
      prolonged period of time. PTX-NPs were hemocompatible and had significant in
      vitro anti-tumoral activity against human primary glioblastoma cell line (U-87
      MG); cytotoxicity was in time- and drug concentration- dependent manner.
      CONCLUSIONS: The developed drug delivery system proved to be suitable for
      intravenous administration. NPs characteristics can be customized to obtain high
      PTX loaded NPs that can improve therapeutic index and avoid an uncontrolled
      release.

PMID- 24939641
TI  - Extremely confined gap surface-plasmon modes excited by electrons.
AB  - High-spatial and energy resolution electron energy-loss spectroscopy (EELS) can
      be used for detailed characterization of localized and propagating surface
      plasmon excitations in metal nanostructures, giving insight into fundamental
      physical phenomena and various plasmonic effects. Here, applying EELS to ultra
      sharp convex grooves in gold, we directly probe extremely confined gap surface
      plasmon (GSP) modes excited by swift electrons in nanometre-wide gaps. We reveal
      the resonance behaviour associated with the excitation of the antisymmetric GSP
      mode for extremely small gap widths, down to ~5 nm. We argue that excitation of
      this mode, featuring very strong absorption, has a crucial role in experimental
      realizations of non-resonant light absorption by ultra-sharp convex grooves with
      fabrication-induced asymmetry. The occurrence of the antisymmetric GSP mode along
      with the fundamental GSP mode exploited in plasmonic waveguides with extreme
      light confinement is a very important factor that should be taken into account in
      the design of nanoplasmonic circuits and devices. 

PMID- 24939640
TI  - A novel strategy for pharmaceutical cocrystal generation without knowledge of
      stoichiometric ratio: myricetin cocrystals and a ternary phase diagram.
AB  - PURPOSE: To develop a streamlined strategy for pharmaceutical cocrystal
      preparation without knowledge of the stoichiometric ratio by preparing and
      characterizing the cocrystals of myricetin (MYR) with four cocrystal coformers
      (CCF). METHODS: An approach based on the phase solubility diagram (PSD) was used
      for MYR cocrystals preparation and the solid-state properties were characterized
      by differential scanning calorimetry (DSC), fourier transform-infrared
      spectroscopy (FT-IR), powder X-ray diffraction (PXRD), and scanning electron
      microscopy (SEM). The ternary phase diagram (TPD) was constructed by combining
      the PSD and nuclear magnetic resonance (NMR) data. After that, the TPD was
      verified by traditional methods. The dissolution of MYR in the four cocrystals
      and pure MYR within three different media were also evaluated. RESULTS: A simple
      research method for MYR cocrystal preparation was obtained as follows: first, the
      PSD of MYR and CCF was constructed and analyzed; second, by transforming the
      curve in the PSD to a TPD, a region of pure cocrystals formation was exhibited,
      and then MYR cocrystals were prepared and identified by DSC, FT-IR, PXRD, and
      SEM; third, with the composition of the prepared cocrystal from NMR, the TPD of
      the MYR-CCF-Solvent system was constructed. The powder dissolution data showed
      that the solubility and dissolution rate of MYR was significantly enhanced by the
      cocrystals. CONCLUSIONS: A novel strategy for pharmaceutical cocrystals
      preparation without knowledge of the stoichiometric ratio based on the TPD was
      established and MYR cocrystals were successfully prepared. The present study
      provides a systematic approach for pharmaceutical cocrystal generation, which
      benefits the development and application of cocrystal technology in drug
      delivery.

PMID- 24939642
TI  - Impact of a telenursing service on satisfaction and health outcomes of children
      with inflammatory rheumatic diseases and their families: a crossover randomized
      trial study protocol.
AB  - BACKGROUND: Pediatric rheumatic diseases have a significant impact on children's
      quality of life and family functioning. Disease control and management of the
      symptoms are important to minimize disability and pain. Specialist clinical
      nurses play a key role in supporting medical teams, recognizing poor disease
      control and the need for treatment changes, providing a resource to patients on
      treatment options and access to additional support and advice, and identifying
      best practices to achieve optimal outcomes for patients and their families. This
      highlights the importance of investigating follow-up telenursing (TN)
      consultations with experienced, specialist clinical nurses in rheumatology to
      provide this support to children and their families. METHODS/DESIGN: This
      randomized crossover, experimental longitudinal study will compare the effects of
      standard care against a novel telenursing consultation on children's and family
      outcomes. It will examine children below 16 years old, recently diagnosed with
      inflammatory rheumatic diseases, who attend the pediatric rheumatology outpatient
      clinic of a tertiary referral hospital in western Switzerland, and one of their
      parents. The telenursing consultation, at least once a month, by a qualified,
      experienced, specialist nurse in pediatric rheumatology will consist of providing
      affective support, health information, and aid to decision-making. Cox's
      Interaction Model of Client Health Behavior serves as the theoretical framework
      for this study. The primary outcome measure is satisfaction and this will be
      assessed using mixed methods (quantitative and qualitative data). Secondary
      outcome measures include disease activity, quality of life, adherence to
      treatment, use of the telenursing service, and cost. We plan to enroll 56
      children. DISCUSSION: The telenursing consultation is designed to support parents
      and children/adolescents during the course of the disease with regular follow-up.
      This project is novel because it is based on a theoretical standardized
      intervention, yet it allows for individualized care. We expect this trial to
      confirm the importance of support by a clinical specialist nurse in improving
      outcomes for children and adolescents with inflammatory rheumatisms. TRIAL
      REGISTRATION: ClinicalTrial.gov identifier: NCT01511341 (December 1st, 2012).

PMID- 24939644
TI  - Improving communication in the primary care setting: perspectives of patients
      with speech disabilities.
AB  - BACKGROUND: Patients with speech disabilities can present with challenges when
      communicating during primary-care clinical encounters. Little is known about the
      healthcare communication experiences of patients with severe speech disabilities.
      METHODS: Twelve participants took part in open-ended, in-person interviews. All
      participants had either acquired or developmental, severe speech disabilities but
      were not limited by cognitive and language disabilities. A multi-disciplinary
      team conducted a thematic analysis that included reading the transcripts and then
      developing and applying a list of codes through consensus. RESULTS: Participants
      discussed provider behaviors that affected communication during clinical
      encounters. They wanted providers to acknowledge their competence by speaking
      directly to them and using age-appropriate language. Additionally, participants
      appreciated when providers adapted to their communication style by maintaining
      eye contact, asking the patient how to best communicate with them, providing time
      for the patient to communicate, not interrupting the patient, and admitting when
      they do not understand the patient. CONCLUSION: Primary-care providers need to be
      cognizant of the communication needs of patients with communication disabilities.
      While the needs might be similar to other patient populations, patients with
      communication disabilities present with unique challenges. With accommodations,
      patients with speech disabilities can potentially be more engaged in their
      healthcare conversations.

PMID- 24939643
TI  - Oncogenic Ras/ERK signaling activates CDCP1 to promote tumor invasion and
      metastasis.
AB  - Involvement of Ras in cancer initiation is known, but recent evidence indicates a
      role in cancer progression, including metastasis and invasion; however, the
      mechanism is still unknown. In this study, it was determined that human lung
      cancer cells with Ras mutations, among other popular mutations, showed
      significantly higher expression of CUB domain-containing protein 1 (CDCP1) than
      those without. Furthermore, activated Ras clearly induced CDCP1, whereas CDCP1
      knockdown or inhibition of CDCP1 phosphorylation by Src-directed therapy
      abrogated anoikis resistance, migration, and invasion induced by activated-Ras.
      Activation of MMP2 and secretion of MMP9, in a model of Ras-induced invasion, was
      found to be regulated through induction of phosphorylated CDCP1. Thus, CDCP1 is
      required for the functional link between Ras and Src signaling during the
      multistage development of human malignant tumors, highlighting CDCP1 as a potent
      target for treatment in the broad spectrum of human cancers associated with these
      oncogenes. IMPLICATIONS: CDCP1 protein induced by oncogenic Ras/Erk signaling is
      essential for Ras-mediated metastatic potential of cancer cells.

PMID- 24939645
TI  - Conducting an antidepressant clinical trial in oncology: challenges and
      strategies to address them.
AB  - OBJECTIVE: The aim of this report is to discuss the design of an antidepressant
      clinical trial and discuss the challenges and potential solutions to these
      challenges to successful recruitment of oncology patients for psychopharmacology
      trials. METHOD: We utilize meeting minutes and investigator discussions to
      identify the modifiable and nonmodifiable variables that affected successful
      subject recruitment for this study. RESULTS: No subjects were enrolled in our
      placebo-controlled antidepressant trial. After study modification to remove the
      placebo arm, we enrolled 21 subjects with depression and cancer. We identified
      the following recruitment difficulties during the study: diagnostic ambiguity in
      patients with depression and cancer, lowered subject retention in a medically ill
      population, patient reluctance to enroll in placebo-controlled studies and lack
      of a standardized referral processes for antidepressant studies in oncology at
      our institution. CONCLUSION: Our experience provides guidance on specific factors
      that future clinicians and researchers can consider when implementing
      psychopharmacologic trials in the medically ill.

PMID- 24939646
TI  - [Elevation of pancreatic enzymes and facial edema. DRESS syndrome].

PMID- 24939647
TI  - A legume product fermented by Saccharomyces cerevisiae modulates cutaneous atopic
      dermatitis-like inflammation in mice.
AB  - BACKGROUND: Isoflavone-containing soy products modulate allergic inflammation in
      mice. In our previously study, IFN-gamma and IL-10 production increased in mice
      fed with Saccharomyces cerevisiae legume fermented product (SCLFP), demonstrating
      that SCLFP had immunomodulatory activity. In this study, we tested the anti
      inflammatory effects of SCLFP in a mouse model of cutaneous atopic dermatitis
      inflammation induced by epicutaneous sensitization. METHODS: Epicutaneous
      exposure to protein allergens plus Staphylococcal enterotoxin B induced a T
      helper (Th)-2-dominant immune response as well as cutaneous atopic dermatitis
      like inflammation in BALB/c mice. The thickness of the skin epithelium,
      eosinophil migration, and T helper responses were determined in patched skin and
      draining lymph nodes of mice fed with and without SCLFP. RESULTS: Epicutaneous
      exposure to protein allergens plus Staphylococcal enterotoxin B induced a T
      helper (Th)-2-dominant immune response as well as cutaneous atopic dermatitis
      like inflammation in BALB/c mice. SCLFP feeding attenuated this cutaneous Th2
      response, as evidenced by decreased thickening of the epidermis, less eosinophil
      infiltration, and lower levels of IL-5, IL-13, and CXCL11 expression compared to
      controls. Oral administration of SCLFP also modulated Th1 responses in draining
      lymph nodes, with lower levels of IFN-gamma, IL-4, and IL-17 expression.
      CONCLUSION: Oral intake of SCLFP modulated the induced Th2 inflammatory responses
      in skin and might have potential applications for the prevention and treatment of
      atopic dermatitis.

PMID- 24939648
TI  - Statistical analysis plan for the Stroke Oxygen Study (SO2S): a multi-center
      randomized controlled trial to assess whether routine oxygen supplementation in
      the first 72 hours after a stroke improves long-term outcome.
AB  - BACKGROUND: The Stroke Oxygen Study (SO2S) is a multi-center randomized
      controlled trial of oxygen supplementation in patients with acute stroke. The
      main hypothesis for the trial is that fixed-dose oxygen treatment during the
      first 3 days after an acute stroke improves outcome. The secondary hypothesis is
      that restricting oxygen supplementation to night time only is more effective than
      continuous supplementation. This paper describes the statistical analysis plan
      for the study. METHODS AND DESIGN: Patients (n = 8000) are randomized to three
      groups: (1) continuous oxygen supplementation for 72 hours; (2) nocturnal oxygen
      supplementation for three nights; and (3) no routine oxygen supplementation.
      Outcomes are recorded at 7 days, 90 days, 6 months, and 12 months. The primary
      outcome measure is the modified Rankin scale at 90 days. Data will be analyzed
      according to the intention-to-treat principle. Methods of statistical analysis
      are described, including the handling of missing data, the covariates used in
      adjusted analyses, planned subgroups analyses, and planned sensitivity analyses.
      TRIAL REGISTRATION: This trial is registered with the ISRCTN register, number
      ISRCTN52416964 (30 September 2005).

PMID- 24939650
TI  - Bedside cardiac testing in acute cor pulmonale.
AB  - We present a case where an ECG and echocardiogram suggested pulmonary embolism
      and early treatment led to a positive outcome. 

PMID- 24939649
TI  - Evidence for lysine acetylation in the coat protein of a polerovirus.
AB  - Virions of the RPV strain of Cereal yellow dwarf virus-RPV were purified from
      infected oat tissue and analysed by MS. Two conserved residues, K147 and K181, in
      the virus coat protein, were confidently identified to contain epsilon-N-acetyl
      groups. While no functional data are available for K147, K181 lies within an
      interfacial region critical for virion assembly and stability. The signature
      immonium ion at m/z 126.0919 demonstrated the presence of N-acetyllysine, and the
      sequence fragment ions enabled an unambiguous assignment of the epsilon-N-acetyl
      modification on K181. We hypothesize that selection favours acetylation of K181
      in a fraction of coat protein monomers to stabilize the capsid by promoting
      intermonomer salt bridge formation. 

PMID- 24939651
TI  - Trapping of single nano-objects in dynamic temperature fields.
AB  - In this article we explore the dynamics of a Brownian particle in a feedback-free
      dynamic thermophoretic trap. The trap contains a focused laser beam heating a
      circular gold structure locally and creating a repulsive thermal potential for a
      Brownian particle. In order to confine a particle the heating beam is steered
      along the circumference of the gold structure leading to a non-trivial motion of
      the particle. We theoretically find a stability condition by switching to a
      rotating frame, where the laser beam is at rest. Particle trajectories and stable
      points are calculated as a function of the laser rotation frequency and are
      experimentally confirmed. Additionally, the effect of Brownian motion is
      considered. The present study complements the dynamic thermophoretic trapping
      with a theoretical basis and will enhance the applicability in micro- and
      nanofluidic devices. 

PMID- 24939652
TI  - Calibration of in vitro multidrug resistance protein 1 substrate and inhibition
      assays as a basis to support the prediction of clinically relevant interactions
      in vivo.
AB  - The multidrug resistance protein 1 (MDR1) is known to limit brain penetration of
      drugs and play a key role in drug-drug interactions (DDIs). Theoretical cut-offs
      from regulatory guidelines are used to extrapolate MDR1 interactions from in
      vitro to in vivo. However, these cut-offs do not account for interlaboratory
      variability. Our aim was to calibrate our experimental system to allow better in
      vivo predictions. We selected 166 central nervous system (CNS) and non-CNS drugs
      to calibrate the MDR1 transport screening assay using Lewis lung cancer porcine
      kidney 1 epithelial cells overexpressing MDR1 (L-MDR1). A threshold efflux ratio
      (ER) of 2 was established as one parameter to assess brain penetration in lead
      optimization. The inhibitory potential of 57 molecules was evaluated using IC50
      values based on the digoxin ER-IC50(ER)-or apparent permeability-IC50(Papp)-in L
      MDR1 cells. Published clinical data for 68 DDIs involving digoxin as the victim
      drug were collected. DDI risk assessments were based on intestinal concentrations
      ([I2]) as well as unbound [I1u] and total plasma [I1T] concentrations. A receiver
      operating characteristic analysis identified an [I2]/IC50(ER) of 6.5 as the best
      predictor of a potential interaction with digoxin in patients. The model was
      further evaluated with a test set of 11 digoxin DDIs and 16 nondigoxin DDIs,
      resulting in only one false negative for each test set, no false positives among
      the digoxin DDIs, and two among the nondigoxin DDIs. Future refinements might
      include using cerebrospinal fluid to unbound plasma concentration ratios rather
      than therapeutic class, better estimation of [I2], and dynamic modeling of MDR1
      mediated DDIs. 

PMID- 24939653
TI  - A numerical method for analysis of in vitro time-dependent inhibition data. Part
      2. Application to experimental data.
AB  - Time-dependent inhibition (TDI) of cytochrome P450 enzymes is an important cause
      of drug-drug interactions. The standard approach to characterize the kinetics of
      TDI is to determine the rate of enzyme loss, kobs, at various inhibitor
      concentrations, [I], and replot the kobs versus [I] to obtain the key kinetic
      parameters, KI and kinact. In our companion manuscript (Part 1; Nagar et al.,
      2014) in this issue of Drug Metabolism and Disposition, we used simulated
      datasets to develop and test a new numerical method to analyze in vitro TDI data.
      Here, we have applied this numerical method to five TDI datasets. Experimental
      datasets include the inactivation of CYP2B6, CYP2C8, and CYP3A4. None of the
      datasets exhibited Michaelis-Menten-only kinetics, and the numerical method
      allowed use of more complex models to fit each dataset. Quasi-irreversible as
      well as partial inhibition kinetics were observed and parameterized. Three
      datasets required the use of a multiple-inhibitor binding model. The mechanistic
      and clinical implications provided by these analyses are discussed. Together with
      the results in Part 1, we have developed and applied a new numerical method for
      analysis of in vitro TDI data. This method appears to be generally applicable to
      model in vitro TDI data with atypical and complex kinetic schemes. 

PMID- 24939654
TI  - A numerical method for analysis of in vitro time-dependent inhibition data. Part
      1. Theoretical considerations.
AB  - Inhibition of cytochromes P450 by time-dependent inhibitors (TDI) is a major
      cause of clinical drug-drug interactions. It is often difficult to predict in
      vivo drug interactions based on in vitro TDI data. In part 1 of these
      manuscripts, we describe a numerical method that can directly estimate TDI
      parameters for a number of kinetic schemes. Datasets were simulated for Michaelis
      Menten (MM) and several atypical kinetic schemes. Ordinary differential equations
      were solved directly to parameterize kinetic constants. For MM kinetics, much
      better estimates of KI can be obtained with the numerical method, and even IC50
      shift data can provide meaningful estimates of TDI kinetic parameters. The
      standard replot method can be modified to fit non-MM data, but normal
      experimental error precludes this approach. Non-MM kinetic schemes can be easily
      incorporated into the numerical method, and the numerical method consistently
      predicts the correct model at errors of 10% or less. Quasi-irreversible
      inactivation and partial inactivation can be modeled easily with the numerical
      method. The utility of the numerical method for the analyses of experimental TDI
      data is provided in our companion manuscript in this issue of Drug Metabolism and
      Disposition (Korzekwa et al., 2014b). 

PMID- 24939655
TI  - Attitudes of family physicians towards adolescent cannabis users: a qualitative
      study in France.
AB  - BACKGROUND: GPs are the health professionals most frequently consulted by
      adolescents. However, discussion between GPs and adolescents regarding cannabis
      use does not occur spontaneously. OBJECTIVE: To identify obstacles to the
      identification and management of cannabis use by adolescents based on GPs'
      experiences. METHODS: We conducted a qualitative study using focus groups of GPs
      from the Auvergne area (France). The GPs were selected according to descriptive
      and strategic variables. Three researchers--an anthropologist, a psychiatrist
      with expertise in addiction and a GP--performed a thematic analysis. RESULTS:
      Twenty-four GPs participated in three consecutive focus groups. The GPs were
      aware of the health risks of cannabis, yet ambivalent about its use by
      adolescents. The GPs also reported a lack of patient questioning during
      consultation. The obstacles to the identification and treatment of cannabis use
      by adolescents identified included lack of GP knowledge about cannabis (e.g.
      consumption patterns and laws); difficulties in addressing the issue with
      adolescents, evaluating adolescents' consumption and its impact and proposing
      support and follow-up and the presence of parents. The GPs were aware that their
      role lies at the intersection between the medical, personal, familial and social
      fields. CONCLUSION: Despite these barriers, GPs are willing to ask adolescents
      about their cannabis use. An adolescent's awareness, environment and
      receptiveness favour a sustainable therapeutic relationship. Brief intervention
      is a tool that may be of assistance in this relationship and allow GPs to take
      the initiative.

PMID- 24939657
TI  - The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic
      craniofacial aggressive B-cell lymphomas.
AB  - To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic
      craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11
      consecutive German High-Grade Non-Hodgkin Lymphoma Study Group trials. ECFI
      occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main
      nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In
      a multivariable analysis adjusted for International Prognostic Index rituximab
      improved event-free and overall survival both in patients with and without ECFI.
      Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P
      = .351) rates were similar in 145 patients receiving and 57 not receiving
      radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous
      system (CNS) disease was increased in 205 ECFI patients compared with 2586 non
      ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with
      rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-ECFI patients; P = .682). In 88
      ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year
      rate of CNS disease was 4.2% compared with 2.3% in 191 patients who did not (P =
      .981). In conclusion, rituximab eliminates the increased risk for CNS disease in
      patients with ECFI. This retrospective analysis does not support intrathecal
      prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed
      complete remission. These findings should be confirmed in a prospective study. 

PMID- 24939658
TI  - Outcome prediction in plasmacytoma of bone: a risk model utilizing bone marrow
      flow cytometry and light-chain analysis.
AB  - The purpose of this study was to use multiparameter flow cytometry to detect
      occult marrow disease (OMD) in patients with solitary plasmacytoma of bone and
      assess its value in predicting outcome. Aberrant phenotype plasma cells were
      demonstrable in 34 of 50 (68%) patients and comprised a median of 0.52% of bone
      marrow leukocytes. With a median follow-up of 3.7 years, 28 of 50 patients have
      progressed with a median time to progression (TTP) of 18 months. Progression was
      documented in 72% of patients with OMD vs 12.5% without (median TTP, 26 months vs
      not reached; P = .003). Monoclonal urinary light chains (ULC) were similarly
      predictive of outcome because progression was documented in 91% vs 44% without
      (median TTP, 16 vs 82 months; P < .001). By using both parameters, it was
      possible to define patients with an excellent outcome (lacking both OMD and ULC,
      7.7% progression) and high-risk patients (OMD and/or ULC, 75% progression; P =
      .001). Trials of systemic therapy are warranted in high-risk patients. 

PMID- 24939656
TI  - The effects of intestinal tract bacterial diversity on mortality following
      allogeneic hematopoietic stem cell transplantation.
AB  - Highly diverse bacterial populations inhabit the gastrointestinal tract and
      modulate host inflammation and promote immune tolerance. In allogeneic
      hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa
      is damaged, and colonizing bacteria are impacted, leading to an impaired
      intestinal microbiota with reduced diversity. We examined the impact of
      intestinal diversity on subsequent mortality outcomes following transplantation.
      Fecal specimens were collected from 80 recipients of allo-HSCT at the time of
      stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and
      microbial diversity was estimated using the inverse Simpson index. Subjects were
      classified into high, intermediate, and low diversity groups and assessed for
      differences in outcomes. Mortality outcomes were significantly worse in patients
      with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and
      67% for low, intermediate, and high diversity groups, respectively (P = .019, log
      rank test). Low diversity showed a strong effect on mortality after multivariate
      adjustment for other clinical predictors (transplant related mortality: adjusted
      hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal
      microbiota at engraftment is an independent predictor of mortality in allo-HSCT
      recipients. These results indicate that the intestinal microbiota may be an
      important factor in the success or failure in allo-HSCT. 

PMID- 24939659
TI  - Thermodynamic properties of the beta-glucosidase from Thermotoga maritima extend
      the upper limit of thermophilicity.
AB  - Enzymes from thermophilic organisms are believed to be strong candidates for
      industrial applications due to their ability to withstand temperature-induced
      enzyme inactivation. The present study demonstrated molecular cloning, over
      expression, purification and characterization of beta-glucosidase from Thermotoga
      maritima. The bglA gene with a capacity to encode a 51 kDa enzyme was
      heterologously expressed in E. coli M15. The enzyme was produced @130 mgL(-1) in
      LB media and @440 mgL(-1) in Dubos salt medium accounting 40-47 % of total
      cellular soluble proteins when lactose was used as an inducer. The enzyme showed
      a peak activity between pH and temperature range of 5.0-7.0 and 80-100  degrees
      C, respectively. The activity was fairly stable up to 140  degrees C. The
      turnover rate (kcat) of the enzyme was 187.1+/-20 s(-1), whereas the Km and Vmax
      values were 0.56 mM and 238+/-2.4 IU mg(-1) protein, respectively. The enzyme was
      shown to have half-life of 136, 71 and 12.6 h at 80, 90 and 100  degrees C,
      respectively. Thermodynamics parameters including melting temperature (130 
      degrees C), activation energy for inactivation (36.92 kJmole(-1)), enthalpy
      (33.73 kJmole(-1)), Gibb's free energy (127.96 kJmole(-1)) and entropy (-246.46
      Jmole(-1)K(-1)) have shown that the enzyme have enhanced hydrophobic interactions
      to prevent its thermal unfolding. These features endorse the industrial
      applications of the enzyme.

PMID- 24939660
TI  - A single-chain-variable-fragment fluorescence biosensor activates fluorogens from
      dissimilar chemical families.
AB  - Current advancements in biological protein discovery utilize bi-partite methods
      of fluorescence detection where chromophore and scaffold are uncoupled. One such
      technology, called fluorogen-activating proteins (FAPs), consists of single-chain
      variable-fragments (scFvs) selected against small organic molecules (fluorogens)
      that are non-fluorescent in solution, but highly fluorescent when bound to the
      scFv. In unusual circumstances a scFv may activate similar fluorogens from a
      single chemical family. In this report we identified a scFv biosensor with
      fluorescence activity against multiple fluorogens from two structurally
      dissimilar families. In-vitro analysis revealed highly selective scFv-ligand
      interactions at sub-micromolar ranges. Additionally, each scFv-fluorogen complex
      possesses unique excitation and emission spectra, which allows broader detection
      limits from the biosensor. Further analysis indicated that ligand activation,
      regardless of chemical family, occurs at a common scFv binding region that proves
      flexible, yet selective for fluorogen binding. As a protein reporter at the
      surface of mammalian cells, the scFv revealed bright signal detection and minimal
      background. Additionally, when tagged to a G-protein-coupled receptor, we
      observed agonist dependent signaling leading to protein traffic from cell surface
      to endosomes via multi-color fluorescence tracking. In summary, this report
      unveils a noncanonical scFv biosensor with properties of high ligand affinity and
      multi-channel fluorescence detection, which consequently offers expanded
      opportunities for cellular protein discovery.

PMID- 24939662
TI  - Ornithine decarboxylase of Leishmania donovani: biochemical properties and
      possible role of N-terminal extension.
AB  - Leishmaniasis is a wide spread tropical disease caused by protozoan parasite
      Leishmania which belongs to order kinetoplastida and family trypanosomatidae.
      Ornithine decarboxylase is key enzyme in polyamine biosynthesis in Leishmania
      donovani. Here, we report biochemical characterization of ornithine decarboxylase
      from L. donovani. Furthermore, we have also investigated the role of N-terminal
      extension (250 amino acids) found in ornithine decarboxylase of L. donovani
      (LdODC). The removal of N-terminal extended region of LdODC results in improved
      stability of the protein. However, the truncated LdODC does not show any
      activity. Apparently, while N-terminal extended region of LdODC helps in proper
      folding of the protein for catalytic activity, there is a stability trade-off.
      The native full length LdODC with N-terminal extension has activity but lower
      stability. Thus, there is trade off of conformational stability for enzyme
      activity. Comparison of biochemical properties of both, fulllength and truncated
      enzymes, have provided interesting insights about the role of N-terminal
      extension in the protein. 

PMID- 24939661
TI  - Development of a Norovirus P particle platform for eliciting neutralizing
      antibody responses to the membrane proximal external region of human
      immunodeficiency virus type 1 envelope.
AB  - Eliciting efficient broadly neutralizing antibodies (BnAbs) is an important goal
      that has yet to be achieved for human immunodeficiency type 1 (HIV-1) vaccine
      development, although they are rarely produced in virus-infected individuals. In
      particular, inducing specific neutralizing antibodies to the gp41 membrane
      proximal external region (MPER) has proven a difficult task. In this study, we
      introduce Norovirus P particles as a new platform to display the MPER epitope of
      HIV-1 as a vaccine with the aim of enhancing immune responses. The results showed
      that HIV-1 chimeric P particles were capable of inducing MPER-specific antibody
      responses in immunized guinea pigs, although only weakly neutralizing activity
      could be detected. These findings are consistent with other previous studies
      which have also focused on the well-studied 2F5 and 4E10 BnAbs. Our findings
      provide an alternate strategy for design of vaccines against HIV-1. However,
      great challenges remain in the effort to develop vaccines that can induce
      efficient HIV-1 neutralizing antibodies. 

PMID- 24939663
TI  - The impact of different footwear characteristics, of a ballet flat pump, on
      centre of pressure progression and perceived comfort.
AB  - BACKGROUND: Uncomfortable shoes have been attributed to poor fit and the cause of
      foot pathologies. Assessing and evaluating comfort and fit have proven
      challenging due to the subjective nature. The aim of this paper is to investigate
      the relationship between footwear characteristics and perceived comfort. METHODS:
      Twenty-seven females assessed three different styles of ballet pump shoe for
      comfort using a comfort scale whilst walking along a 20 m walkway. The physical
      characteristics of the shoes and the progression of centre of pressure during
      walking were assessed. RESULTS: There were significant physical differences
      between each style, square shoe being the shortest, widest and stiffest and round
      shoe having the least volume at the toe box. Centre of pressure progression angle
      was centralised to the longitudinal axis of the foot when wearing each of the
      three shoes compared to barefoot. Length, width and cantilever bending stiffness
      had no impact on perceived comfort. CONCLUSION: Wearing snug fitting flexible
      soled round ballet flat pump is perceived to be the most comfortable of the shoe
      shapes tested producing a faster more efficient gait. Further investigations are
      required to assess impact/fit and upper material on perceived comfort to aid
      consumers with painful feet in purchasing shoes.

PMID- 24939664
TI  - Development of an automated measure of iliac artery tortuosity that successfully
      predicts early graft-related complications associated with endovascular aneurysm
      repair.
AB  - OBJECTIVES: Iliac artery tortuosity has been linked to the likelihood of
      complications following endovascular aneurysm repair (EVAR). Measures of
      tortuosity can be established from CT images; however, the reproducibility of
      existing scoring techniques has not been clearly established. It remains unclear
      whether it is tortuosity at focal locations or for the vessel as a whole that is
      most relevant to adverse events. The two aims of this study were to develop an
      automated measure of iliac artery tortuosity to assist with surgical planning by
      providing an objective assessment of procedural difficulty, and to correlate this
      measure with early postoperative outcomes. DESIGN AND METHODS: Unlike existing
      approaches, the present measure of tortuosity considers spatial scale, which
      incorporates the effects of local anatomy. A computerized imaging algorithm was
      used to segment vasculature and establish a medial line and vascular boundary
      from contrast enhanced CT scans of 150 patients undergoing EVAR. Two tortuosity
      measures were examined: curvature and vessel to straight-line length (L1/L2
      ratio). For a given spatial scale, the maximum tortuosity was computed on both
      iliac arteries and the artery with the lower maximum was selected for analysis.
      Correlation of tortuosity with early (<30 day) and longer-term graft-related
      complications was assessed. RESULTS: Maximal tortuosity at a 10 mm scale was a
      significant predictor of early (<30 day) complications (p = .016 for curvature
      and p = .006 for L1/L2-ratio), but not of long-term complications. Aneurysmal
      diameter was independent of tortuosity (Pearson's r value = -.006). CONCLUSION:
      The results demonstrate that, at a local scale, tortuosity measures are
      correlated with early outcomes. The spatial scale at which tortuosity is measured
      is important. The optimal scale of 10 mm implies that adverse events could be
      linked to a focal anatomical location.

PMID- 24939665
TI  - Renaissance of electrosynthetic methods for the construction of complex
      molecules.
AB  - Current affairs: Efficient N,N dimerization by using an electric current is a
      recent powerful example of preparative electrosynthesis where conventional
      reagents fail. The general and practical nature of this method as well as other
      applications will breathe new life into the electroorganic synthesis of complex
      molecules. 

PMID- 24939666
TI  - The effect of ventilation on indoor exposure to semivolatile organic compounds.
AB  - A mechanistic model was developed to examine how natural ventilation influences
      residential indoor exposure to semivolatile organic compounds (SVOCs) via
      inhalation, dermal sorption, and dust ingestion. The effect of ventilation on
      indoor particle mass concentration and mass transfer at source/sink surfaces, and
      the enhancing effect of particles on mass transfer at source/sink surfaces are
      included. When air exchange rate increases from 0.6/h to 1.8/h, the steady-state
      SVOC (gas-phase plus particle phase with log KOA varying from 9 to 13)
      concentration in the idealized model decreases by about 60%. In contrast, for the
      same change in ventilation, the simulated indoor formaldehyde (representing
      volatile organic compounds) gas-phase concentration decreases by about 70%. The
      effect of ventilation on exposure via each pathway has a relatively insignificant
      association with the KOA of the SVOCs: a change of KOA from 10(9) to 10(13)
      results in a change of only 2-30%. Sensitivity analysis identifies the deposition
      rate of PM2.5 as a primary factor influencing the relationship between
      ventilation and exposure for SVOCs with log KOA = 13. The relationship between
      ventilation rate and air speed near surfaces needs to be further substantiated.

PMID- 24939667
TI  - Ultrafast and versatile spectroscopy by temporal Fourier transform.
AB  - One of the most remarkable and useful properties of a spatially converging lens
      system is its inherent ability to perform the Fourier transform; the same applies
      for the time-lens system. At the back focal plane of the time-lens, the spectral
      information can be instantaneously obtained in the time axis. By implementing
      temporal Fourier transform for spectroscopy applications, this time-lens-based
      architecture can provide orders of magnitude improvement over the state-of-art
      spatial-dispersion-based spectroscopy in terms of the frame rate. On the other
      hand, in addition to the single-lens structure, the multi-lens structures (e.g.
      telescope or wide-angle scope) will provide very versatile operating conditions.
      Leveraging the merit of instantaneous response, as well as the flexible lens
      structure, here we present a 100-MHz frame rate spectroscopy system - the
      parametric spectro-temporal analyzer (PASTA), which achieves 17 times zoom in/out
      ratio for different observation ranges. 

PMID- 24939668
TI  - Chemical and mechanical signals in inducing Phormidium (Cyanobacteria) defence
      against their grazers.
AB  - The nature of stimuli evoking cyanobacterium defence was investigated in
      experiments on Phormidium sp. strain able to defend itself against ciliate
      grazers. Limited dispersion of trichomes in reaction to Pseudomicrothorax dubius
      separated from cyanobacterium with a mesh insert indicates the existence of a
      chemical cue originating from the ciliates. Grazers released into the wells where
      trichomes' dispersion was already limited by the cue initially had no difficulty
      finding food, but started to starve 24 h later. Similar situation was observed in
      control wells. Direct observations of trichomes attacked by the ciliates showed a
      distinct difference between the trichomes previously subjected to mesh-separated
      ciliate and the control ones. The former withdrew more frequently into a rigid
      sheath, whereas the latter usually withdrew into elastic tubes. This suggests
      that both chemical and mechanical stimuli are necessary to express cyanobacterium
      defence to the fullest extent. Further investigations showed that ciliates
      specialised in ingesting filamentous Cyanobacteria limit trichomes' dispersion,
      whereas filter-feeding Euplotes and Cyanobacteria-feeding rotifer do not. The
      cyanobacterium can detect grazer presence even without direct contact and modify
      its morphology in a way enabling full expression of defence reaction. This is the
      first report on ciliate-cyanobacterium chemical mediation. 

PMID- 24939669
TI  - Direct measurement of aortic regurgitation with phase-contrast magnetic resonance
      is inaccurate: proposal of an alternative method of quantification.
AB  - BACKGROUND: Phase-contrast magnetic resonance (MR) has been widely used for
      quantification of aortic regurgitation. However there is significant practice
      variability regarding where and how the blood flow data are acquired. OBJECTIVE:
      To compare the accuracy of flow quantification of aortic regurgitation at three
      levels: the ascending aorta at the level of the right pulmonary artery (level 1),
      the aortic valve hinge points at end-diastole (level 2) and the aortic valve
      hinge points at end-systole (level 3). MATERIALS AND METHODS: We performed
      cardiovascular MR in 43 children with aortic regurgitation. By using phase
      contrast MR, we measured the systolic forward, diastolic retrograde and net
      forward flow volume indices at three levels. At each level, the following
      comparisons were made: (1) systolic forward flow volume index (FFVI) versus left
      ventricular cardiac index (LVCI) measured by cine ventricular volumetry; (2)
      retrograde flow volume index (RFVI) versus estimated aortic regurgitation volume
      index (which equals LVCI minus pulmonary blood flow index [QPI]); (3) net forward
      flow volume index (NFVI) versus pulmonary blood flow index. RESULTS: The forward
      flow volume index, retrograde flow volume index and net forward flow volume index
      measured at each of the three levels were significantly different except for the
      retrograde flow volume index measured at levels 1 and 3. There were good
      correlations between the forward flow volume index and the left ventricular
      cardiac index at all three levels, with measurement at level 2 showing the best
      correlation. Compared to the forward flow volume indices, the retrograde flow
      volume index had a lower correlation with the estimated aortic regurgitation
      volume indices and had widely dispersed data with larger prediction intervals.
      CONCLUSION: Large variations in systolic forward, diastolic retrograde and net
      forward flow volumes were observed at different levels of the aortic valve and
      ascending aorta. Direct measurement of aortic regurgitation volume and fraction
      is inaccurate and should be abandoned. Instead, calculation of the aortic
      regurgitation volume from more reliable data is advised. We recommend subtracting
      pulmonary blood flow from systolic forward flow measured at the aortic valve
      hinge points at end-diastole as a more accurate and consistent method for
      calculating the volume of aortic regurgitation.

PMID- 24939670
TI  - Ablation of colorectal liver metastases by irreversible electroporation: results
      of the COLDFIRE-I ablate-and-resect study.
AB  - OBJECTIVES: Irreversible electroporation (IRE) is a new ablation technique that
      relies on high-voltage electrical pulses. This clinical study evaluates the
      pathological response of colorectal liver metastases (CRLM) treated with IRE and
      the clinical safety and feasibility. METHODS: Ten patients with resectable CRLM
      were included. During laparotomy, the metastases were treated with IRE and
      resected 60 min later. Safety and feasibility were assessed based on adverse
      events, laboratory values, technical success and intra-operative ultrasound
      findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC)
      vitality staining and (immuno)histochemical stainings (HE, complement-3d and
      caspase-3). RESULTS: Ten lesions with a mean diameter of 2.4 cm were successfully
      electroporated and resected, on average, 84 min later (range 51-153 min). One
      minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a
      sharply demarcated hypoechoic ablation zone around the tumour. TTC showed
      avitality of all lesions, covering the complete tumour in 8/10 lesions. Although
      immunohistochemistry proved heterogeneous and difficult to interpret within the
      tumours, it confirmed irreversible cell damage in the tumour-free margin of all
      specimens. CONCLUSIONS: This ablate-and-resect study demonstrated avitality
      caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour
      specific electrical properties is warranted to improve ablation protocols for
      maximised tissue ablation. KEY POINTS: * Irreversible electroporation induces
      cell death in colorectal liver metastases within 1 h. * The ablation zone shows a
      sharp demarcation between avital and vital tissue. * Apoptosis is involved in
      cell death of colorectal liver metastases after IRE. * Effects of IRE can be
      monitored real-time using intraoperative ultrasound. * Local electrical
      heterogeneities of tumour tissue may require tumour-specific ablation protocols.

PMID- 24939672
TI  - Hidden one-dimensional spin modulation in a three-dimensional metal.
AB  - Pressure can transform a transparent material into an opaque one, quench the
      moments in a magnet and force solids to flow like liquids. At 15 GPa, the
      pressure found 500 km below the earth's surface, the semiconductors silicon and
      germanium superconduct. Yet, at this same pressure, we show here that the
      magnetism in metallic GdSi remains completely robust even as it shrinks by one
      seventh of its volume. Non-resonant X-ray magnetic diffraction in a specially
      designed diamond anvil cell, combined with band structure calculations, reveal
      the stability of the incommensurate spin density wave, which can be traced to a
      persistently nested portion of the Fermi surface that becomes increasingly one
      dimensional under pressure. A cooperative interaction between nested, itinerant
      spins and local magnetic moments provides the organizing principle for the
      modulated magnetic order, salient both for its insights into the role of topology
      in ordered states and its potential functionality. 

PMID- 24939671
TI  - Uric acid: association with rate of renal function decline and time until start
      of dialysis in incident pre-dialysis patients.
AB  - BACKGROUND: In patients with chronic kidney disease (CKD) hyperuricemia is
      common. Evidence that hyperuricemia might also play a causal role in vascular
      disease, hypertension and progression of CKD is accumulating. Therefore, we
      studied the association between baseline uric acid (UA) levels and the rate of
      decline in renal function and time until start of dialysis in pre-dialysis
      patients. METHODS: Data from the PREPARE-2 study were used. The PREPARE-2 study
      is an observational prospective cohort study including incident pre-dialysis
      patients with CKD stages IV-V in the years between 2004 and 2011. Patients were
      followed for a median of 14.9 months until start of dialysis, kidney
      transplantation, death, or censoring. Main outcomes were the change in the rate
      of decline in renal function (measured as estimated glomerular filtration rate
      (eGFR)) estimated using linear mixed models, and time until start of dialysis
      estimated using Cox proportional hazards models. RESULTS: In this analysis 131
      patients were included with a baseline UA level (mean (standard deviation (SD))
      of 8.0 (1.79) mg/dl) and a mean decline in renal function of -1.61 (95%
      confidence interval (CI), -2.01; -1.22) ml/min/1.73 m2/year. The change in
      decline in GFR associated with a unit increase in UA at baseline was -0.14 (95%
      CI -0.61;0.33, p=0.55) ml/min/1.73 m2/year. Adjusted for demography,
      comorbidities, diet, body mass index (BMI), blood pressure, lipids, proteinuria,
      diuretic and/or allopurinol usage the change in decline in eGFR did not change.
      The hazard ratio (HR) for starting dialysis for each mg/dl increase in UA at
      baseline was 1.08 (95% CI, 0.94;1.24, p=0.27). After adjustment for the same
      confounders the HR became significant at 1.26 (95% CI, 1.06;1.49, p=0.01),
      indicating an earlier start of dialysis with higher levels of UA. CONCLUSION:
      Although high UA levels are not associated with an accelerated decline in renal
      function, a high serum UA level in incident pre-dialysis patient is a risk factor
      for an earlier start of dialysis.

PMID- 24939673
TI  - Outdoor air pollution, subtypes and severity of ischemic stroke--a small-area
      level ecological study.
AB  - BACKGROUND: Evidence linking outdoor air pollution and incidence of ischemic
      stroke subtypes and severity is limited. We examined associations between outdoor
      PM10 and NO2 concentrations modeled at a fine spatial resolution and etiological
      and clinical ischemic stroke subtypes and severity of ischemic stroke. METHODS:
      We used a small-area level ecological study design and a stroke register set up
      to capture all incident cases of first ever stroke (1995-2007) occurring in a
      defined geographical area in South London (948 census output areas; population of
      267839). Modeled PM10 and NO2 concentrations were available at a very fine
      spatial scale (20 meter by 20 meter grid point resolution) and were aggregated to
      output area level using postcode population weighted averages. Ischemic stroke
      was classified using the Oxford clinical classification, the Trial of Org 10172
      in Acute Stroke Treatment (TOAST) etiological classification, National Institutes
      of Health Stroke Scale (NIHSS) score and a pragmatic clinical severity
      classification based on Glasgow coma score, ability to swallow, urinary
      continence and death <2 days of stroke onset. RESULTS: Mean (SD) concentrations
      were 25.1 (1.2) ug/m(3) (range 23.3-36.4) for PM10 and 41.4 (3.0) ug/m(3) (range
      35.4-68.0) for NO2. There were 2492 incident cases of ischemic stroke. We found
      no evidence of association between these pollutants and the incidence of ischemic
      stroke subtypes classified using the Oxford and TOAST classifications. We found
      no significant association with stroke severity using NIHSS severity categories.
      However, we found that outdoor concentrations of both PM10 and NO2 appeared to be
      associated with increased incidence of mild but not severe ischemic stroke,
      classified using the pragmatic clinical severity classification. For mild
      ischemic stroke, the rate ratio in the highest PM10 category by tertile was 1.20
      (1.05-1.38) relative to the lowest category. The rate ratio in the highest NO2
      category was 1.22 (1.06-1.40) relative to the lowest category. CONCLUSIONS: We
      found no evidence of association between outdoor PM10 and NO2 concentrations and
      ischemic stroke subtypes but there was a suggestion that living in areas with
      elevated outdoor PM10 and NO2 concentrations might be associated with increased
      incidence of mild, but not severe, ischemic stroke.

PMID- 24939674
TI  - Patients' preferences for bone metastases treatments in France, Germany and the
      United Kingdom.
AB  - PURPOSE: The aim of this study was to assess patients' preferences for efficacy,
      safety, and mode of administration in relation to available bone-targeted agents
      (BTA) for the prevention of skeletal-related events (SREs) associated with bone
      metastases in Europe. METHODS: Adults in France (n = 159), Germany (n = 166), and
      the United Kingdom (UK; n = 159) with a self-reported physician diagnosis of bone
      metastases secondary to a solid tumour completed an online discrete- choice
      experiment survey of ten questions, choosing between pairs of hypothetical BTA
      profiles. Profiles were defined by five treatment attributes: delay of first SRE,
      delay of worsening of pain, annual risk of osteonecrosis of the jaw (ONJ), annual
      risk of renal impairment, and mode of administration. Profiles were generated
      using an experimental design with known statistical properties. A main-effects
      random parameters logit (RPL) model was applied to relate participants' choices
      to the characteristics of the BTA profiles. RESULTS: The most important treatment
      attributes for patients across all three countries were time until first SRE,
      annual risk of renal complications and time until pain worsening. For these
      attributes, better levels of outcomes were significantly preferred to worse
      levels (p < 0.05). A 120-minutes infusion every 4 weeks was the least preferred
      mode of administration. Risk of ONJ was judged by patients in the UK and Germany
      to be the least important attribute. CONCLUSIONS: Patients consider delaying
      SREs, avoiding renal impairment and delaying pain worsening as the most important
      goals to consider when selecting treatment to prevent the bone complications
      commonly associated with bone metastases.

PMID- 24939675
TI  - Knee osteoarthritis, body mass index and pain: data from the Osteoarthritis
      Initiative.
AB  - OBJECTIVE: This study aimed to determine whether BMI increases knee pain as
      measured from self-reported surveys even when controlling for OA severity as
      measured by osteophytes and joint space narrowing visible on X-rays. METHODS:
      Data available through the Osteoarthritis Initiative (OAI) were analysed, which
      included a sample of 4769 individuals, to answer the above question regarding OA,
      excess weight and pain. OA severity was assessed through baseline X-rays on right
      knees that were scored on a composite quasi-Kellgren and Lawrence grade. Weight
      was assessed through BMI. Pain was assessed through self-reports of the WOMAC
      pain subset as well as a 30-day pain severity question based on a 0-10 scale.
      Data were analysed using SPSS and analyses of covariance (ANCOVAs) were run to
      examine models adjusted for age, smoking, prior injury, pain medication and
      Heberden's nodes. Critical alpha levels were set at 0.05. RESULTS: The results
      reported here confirm that knee pain does increase with OA severity. However,
      ANCOVA multiple regressions with controls reveal that even when taking into
      account OA severity, individuals with higher BMIs experience greater pain than
      individuals with lower BMIs. CONCLUSION: Weight loss may reduce knee OA pain even
      if the osteological symptoms are not treated.

PMID- 24939676
TI  - Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous
      anti-TNF agents in patients with rheumatoid arthritis?
AB  - OBJECTIVE: The aim of this study was to investigate the influence of the
      pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in
      RA patients. METHODS: Fifty RA patients were prospectively recruited from the
      Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment
      with s.c. anti-TNF agents and having had neither changes in therapy nor local
      corticosteroid injections in the previous 3 months. Patients underwent clinical,
      laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)]
      and US assessment at two time points, i.e. at peak plasma drug concentration and
      at trough plasma drug concentration. US assessments were performed blindly to the
      anti-TNF agent, the administration time and the clinical and laboratory data.
      Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode
      synovitis and synovial power Doppler signal. Global indices for B-mode synovitis
      (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist
      hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler
      US remission as a DSI <1. RESULTS: There were no significant differences between
      the clinical, laboratory and B-mode and Doppler US parameters at peak time and
      trough time (P = 0.132-0.986). There were no significant differences between the
      proportion of patients with active disease and those in remission according to
      DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P
      = 0.070-1). CONCLUSION: Our results suggested that s.c. anti-TNF pharmacokinetics
      do not significantly influence US-scored synovitis in RA patients.

PMID- 24939677
TI  - Impact of different infliximab dose regimens on treatment response and drug
      survival in 462 patients with psoriatic arthritis: results from the nationwide
      registries DANBIO and ICEBIO.
AB  - OBJECTIVE: The aim of this study was to describe dose regimens, dose escalation
      and clinical outcomes in TNF-alpha inhibitor (TNFi)-naive patients with PsA
      treated with infliximab in routine rheumatology care. METHODS: We conducted an
      observational cohort study based on the nationwide Danish Rheumatologic Database
      (DANBIO) and Center for Rheumatology Research (ICEBIO) registries. Stratified by
      country, characteristics of patients treated with <=3 mg infliximab/kg body
      weight, 3-5 mg/kg or >=5 mg/kg every 8 weeks were described. Outcomes were
      evaluated by ACR 20%, 50% and 70% (ACR20/50/70) responses and European League
      Against Rheumatism good response after 6 months, disease activity after 12
      months, Kaplan-Meier plots and regression analyses. RESULTS: Four hundred and
      sixty-two patients (376 Danish, 86 Icelandic) received treatment with infliximab.
      In Danish patients, the starting dose was <=3 mg/kg in 110 patients (29%), 3-5
      mg/kg in 157 (42%), >=5 mg/kg in 38 (10%) and unregistered in 71 (19%). In
      Icelandic patients, corresponding numbers were 64 (74%), 17 (27%), 0 (0%) and 5
      (6%). Patients with a higher body weight received lower doses per kilogram.
      Danish patients received higher doses than Icelandic patients at baseline [median
      3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P < 0.05] and after 12
      months [3.3 (3.0-4.5) vs 2.9 (2.2-3.5) mg/kg, P < 0.0001]. After 12 months, 58%
      of Danish and 66% of Icelandic patients maintained treatment. Danish patients had
      shorter drug survival than Icelandic patients (1183 vs 483 days). In univariate
      analyses stratified by country, time until dose escalation, response rates, drug
      survival and 1-year's disease activity were independent of starting dose. Drug
      survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In
      clinical practice, > 70% of Icelandic and Danish PsA patients treated with
      infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended
      in international guidelines. Lower starting doses did not affect drug survival or
      response.

PMID- 24939678
TI  - Is colour duplex sonography-guided temporal artery biopsy useful in the diagnosis
      of giant cell arteritis? A randomized study.
AB  - OBJECTIVE: The aim of this study was to assess the usefulness of colour duplex
      sonography (CDS)-guided temporal artery biopsy (TAB) for the diagnosis of GCA in
      patients with suspected GCA. METHODS: From September 2009 through December 2012,
      112 consecutive patients with suspected GCA were randomized to undergo CDS-guided
      TAB or standard TAB. All patients underwent temporal artery physical examination
      and temporal artery CDS prior to TAB. CDS of the temporal artery was performed by
      the same ultrasonographer, who was unaware of the patient's clinical data, and
      all TABs were evaluated by the same pathologist. Seven patients in whom biopsy
      failed to sample temporal artery tissue were excluded from the analysis. RESULTS:
      Fifty patients were randomized to undergo CDS-guided TAB and 55 patients to
      standard TAB. Except for a younger age in patients who underwent standard TAB (P
      = 0.026), no significant differences were observed between the two groups. There
      were no significant differences in the frequencies of positive TAB for classic
      transmural inflammation (28% vs 18.2%) or for periadventitial small vessel
      vasculitis and/or vasa vasorum vasculitis (6% vs 14.5%) between the two groups.
      No significant differences in the frequency of positive TAB in the two groups
      were observed when we excluded the patients treated with glucocorticoids and when
      we stratified the patients of the two groups for the presence or absence of the
      halo sign. CONCLUSION: Our study showed that CDS-guided TAB did not improve the
      sensitivity of TAB for diagnosing GCA.

PMID- 24939679
TI  - Immunoendocrinology: faulty hormonal imprinting in the immune system.
AB  - Hormonal imprinting is an epigenetic process which is taking place perinatally at
      the first encounter between the developing hormone receptors and their target
      hormones. The hormonal imprinting influences the binding capacity of receptors,
      the hormone synthesis of the cells, and other hormonally regulated functions, as
      sexual behavior, aggressivity, empathy, etc. However, during the critical period,
      when the window for imprinting is open, molecules similar to the physiological
      imprinters as synthetic hormone analogs, other members of the hormone families,
      environmental pollutants, etc. can cause faulty imprinting with life-long
      consequences. The developing immune system, the cells of which also have
      receptors for hormones, is very sensitive to faulty imprinting, which causes
      alterations in the antibody and cytokine production, in the ratio of immune
      cells, in the defense against bacterial and viral infections as well as against
      malignant tumors. Immune cells (lymphocytes, monocytes, granulocytes and mast
      cells) are also producing hormones which are secreted into the blood circulation
      as well as are transported locally (packed transport). This process is also
      disturbed by faulty imprinting. As immune cells are differentiating during the
      whole life, faulty imprinting could develop any time, however, the most decisive
      is the perinatal imprinting. The faulty imprinting is inherited to the progenies
      in general and especially in the case of immune system. In our modern world the
      number and amount of artificial imprinters (e.g. endocrine disruptors and drugs)
      are enormously increasing. The effects of the faulty imprinters most dangerous to
      the immune system are shown in the paper. The present and future consequences of
      the flood of faulty imprintings are unpredictable however, it is discussed.

PMID- 24939680
TI  - Optimization of triacetylfusarinine C and ferricrocin productions in Aspergillus
      fumigatus.
AB  - Iron is an essential element for all microorganisms. Bacteria and fungi produce
      versatile siderophores for binding and storing this essential transition metal
      when its availability is limited in the environment. The aim of the study was to
      optimize the fermentation medium of Aspergillus fumigatus for siderophore
      production. Triacetyl-fusarinine C and ferricrocin yields were dependent on
      glucose and glycine supplementations as well as the initial pH of the culture
      media. The optimal fermentation medium for triacetylfusarinine C production
      contained 8% glucose, 0.4% glycine and the initial pH was set to 5.9. Meanwhile,
      maximal ferricrocin yields were recorded in the presence of 10% glucose, 0.5%
      glycine and at an initial pH of 7.4. Under optimized fermentation conditions, the
      yields for triacetylfusarinine C and ferricrocin increased up to 2.9 g/l culture
      medium and 18.9 mg/g mycelium, respectively. 

PMID- 24939681
TI  - Use of TaqMan(r) real-time PCR for rapid detection of Salmonella enterica serovar
      Typhi.
AB  - We evaluated the performances of a newly designed real-time polymerase chain
      reaction (PCR) assay using TaqMan(r) probes to detect Salmonella Typhi. TaqMan(r)
      real-time PCR assays were performed by designed primers and probe based on the
      staG gene for detecting S. Typhi. The specificity of the assay was evaluated on
      15 Salmonella serovars. The analytical specificity was evaluated on 20 non
      Salmonella microorganisms. The analytical sensitivity was assessed using
      decreasing DNA quantities of S. Typhi ATCC 19430. Finally the detection
      capability of the TaqMan(r) real-time PCR assay on isolates recovered from
      patients with Salmonella infections was compared to the conventional PCR assay.
      Only S. Typhi strain had positive results when subjected to the assay using Typhi
      specific real-time PCR. No amplification products were observed in real-time PCR
      with any of the non-Salmonella microorganisms tested. The TaqMan(r) real-time PCR
      was more sensitive than the conventional PCR. In conclusion, we found that the
      easy-to-use real-time PCR assays were faster than conventional PCR systems. The
      staG-based TaqMan(r) real-time PCR assay showed to be specific and sensitive
      method for the safe and rapid detection of the S. Typhi. 

PMID- 24939682
TI  - Chitinase but N-acetyl-beta-D-glucosaminidase production correlates to the
      biomass decline in Penicillium and Aspergillus species.
AB  - Hydrolytic enzyme production is typical of the autolysis in filamentous fungi;
      however, less attention has been given to the physiological role of the enzymes.
      Here, the aim was to investigate the possible relation of the chitinolytic
      enzymes to the changes in the biomass in some filamentous fungi of high
      importance for pharmaceutical or food industry. In Penicillium and Aspergillus
      filamentous fungi, which showed different characteristics in submerged cultures,
      the growth and biomass decline rates were calculated and correlated to the
      chitinase and N-acetyl-beta-D-glucosaminidase enzyme productions. Correlation was
      found between the biomass decrease rate and the chitinase level at the stationary
      growth phase; while chitinase production covariates negatively with N-acetyl-beta
      D-glucosaminidase activities. The chitinase production and the intensive
      autolysis hindered the production of N-acetyl-beta-D-glucosaminidase and,
      therefore, could hinder the cell death in the cultures. 

PMID- 24939683
TI  - The in vitro antibacterial effect of S53P4 bioactive glass and gentamicin
      impregnated polymethylmethacrylate beads.
AB  - Osteomyelitis is a disease that is still difficult to treat, with considerable
      morbidity and associated costs. The current "gold standard" in treatment -
      debridement and implantation of antibiotic impregnated polymethylmethacrylate
      (PMMA) beads - presents the disadvantage of a second surgical intervention
      required for the removal of the beads. We comparatively investigated the in vitro
      antibacterial effect of S53P4 bioactive glass (BAG) and gentamicin impregnated
      PMMA beads. Bacterial viability was assessed hourly by Standard Plate Count
      during 24 hours of incubation, by determining the number of colony forming units
      (CFU) of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and
      Klebsiella pneumoniae. Both tested materials showed an antibacterial effect on
      all studied bacteria. In case of S. aureus, BAG granules were almost as effective
      as gentamicin impregnated PMMA beads, with no statistically significant
      differences. In contrast, PMMA beads had a superior antibacterial effect on S.
      epidermidis and K. pneumoniae. The antibacterial effect of BAG was greatly
      influenced by granule size and contact time. There was a statistically
      significant correlation between pH values and the number of CFU in the case of
      S53P4 BAG granules. As a biocompatible and biodegradable bone substitute, S53P4
      bioactive glass can be a good alternative in the local management of
      osteomyelitis. 

PMID- 24939684
TI  - Evaluation of possibilities in identification and susceptibility testing for
      Candida glabrata clinical isolates with the Integral System Yeast Plus (ISYP).
AB  - The aim of this study was to evaluate possibilities of correct identification and
      susceptibility testing of C. glabrata clinical isolates with Integral System
      Yeast Plus (ISYP). For species identification, as the reference method, API
      Candida test and species-specific PCR reactions were used. The potential of
      antifungal susceptibility testing by the ISYP test was compared with the
      Sensititre Yeast One. Whilst the reference methods confirmed that the received
      population (n = 65 isolates) represented only C. glabrata, identification with
      the ISYP system showed correct data only in the case of 18 strains tested
      (27.7%). Species identification of the other 47 strains with the ISYP test was
      not possible at all. Significant differences were also observed for drug
      susceptibility testing carried out by the ISYP and the Sensititre Yeast One. The
      highest level of disagreement in classifying strains as resistant or susceptible
      estimated, as 73.9% and 40.0%, was observed for itraconazole and amphotericin B,
      respectively. Satisfactory results were only obtained for 5-fluorocytosine with
      93.8% agreement between both methods. In our opinion the idea of the ISYP system
      is certainly good. The combination of identification ability and drug
      susceptibility testing in one test is very important, especially from a clinical
      point of view. However, the current version of the ISYP has many disadvantages.
      We would like to encourage the manufacturer to make an effort and develop a new,
      more accurate version of the test. 

PMID- 24939686
TI  - Prevalence of Pneumocystis jirovecii pneumonia (2010-2013): the first Croatian
      report.
AB  - Pneumocystis jirovecii is an important cause of interstitial pneumonia
      particularly among immunocompromised hosts. We analysed the prevalence of P.
      jirovecii pneumonia (PCP) among HIV-infected and HIV-uninfected patients
      presented with interstitial pneumonia or acute respiratory syndrome hospitalized
      in six Croatian tertiary care hospitals. Over four-year period (2010-2013), a
      total of 328 lower respiratory tract samples: 253 (77.1%) bronchoalveolar lavage
      fluid, 43 (13.1%) tracheal aspirates and 32 (9.8%) bronchial aspirates from 290
      patients were examined by real-time polymerase chain reaction (PCR). PCP was
      detected in 23 (7.9%) patients. The prevalence of PCP differed significantly
      among tested groups (chi2 = 95.03; d.f. = 3; p < 0.001). HIV-infected patients
      were more often positive (56.6%, 95%CI = 37.3-72.4) compared to other groups
      (patients with malignant disease 7.7%, 95%CI = 2.6-20.3; transplant patients
      7.7%, 95%CI = 2.2-24.1; patients with other diagnosis 1.5%, 95%CI = 0.5-4.4).
      Majority of HIV-positive patients (80%) were newly diagnosed cases. Our results
      indicate that HIV-infected patients still represents the main risk group for P.
      jirovecii infection. PCP is responsible for pneumonia in 56.6% HIV-positive
      patients in Croatia, primarily those who do not know that they are HIV infected. 

PMID- 24939685
TI  - Serological and molecular capsular typing, antibiotic susceptibility of
      Streptococcus pneumoniae isolates from invasive and non-invasive infections.
AB  - Streptococcus pneumoniae causes life threatening infections and necessitate for
      impediment and controlling disease; to conquer this, information is needed about
      serotype distribution and patterns of antibiotic resistance. The present study
      was to determine the serotype distribution of S. pneumoniae isolated from the
      entire age group individual and to correlate this distribution with
      susceptibility. Cases of pneumococcal infections have been reviewed for
      serotyping and antibiotic susceptibility. Out of 117 pneumococcal isolates 45
      (39%) were penicillin-resistant, 84 (72%) were erythromycin-resistant and 100%
      were co-trimoxazole resistant. The most frequently isolated serotypes were 23F,
      19F, 14, 6B, 5, 6A, 19A and 9V. PCV7, PCV10 and PCV13 coverage was 68%, 79%, 87%,
      respectively. Similarly, there was similarity in PCV7 coverage for non invasive
      isolates (64.5%) and invasive isolates (72.2%). The study state that common
      pneumococcal serotypes were present in similar ways as reported in literature. A
      continuous survey of pneumococcal infected population is requirement and
      necessity for success of vaccination. 

PMID- 24939687
TI  - Toxicity of abiotic stressors to Fusarium species: differences in hydrogen
      peroxide and fungicide tolerance.
AB  - Stress sensitivity of three related phytopathogenic Fusarium species (Fusarium
      graminearum, Fusarium oxysporum and Fusarium verticillioides) to different
      oxidative, osmotic, cell wall, membrane, fungicide stressors and an antifungal
      protein (PAF) were studied in vitro. The most prominent and significant
      differences were found in oxidative stress tolerance: all the three F.
      graminearum strains showed much higher sensitivity to hydrogen peroxide and, to a
      lesser extent, to menadione than the other two species. High sensitivity of F.
      verticillioides strains was also detectable to an azole drug, Ketoconazole.
      Surprisingly, no or limited differences were observed in response to other
      oxidative, osmotic and cell wall stressors. These results indicate that fungal
      oxidative stress response and especially the response to hydrogen peroxide (this
      compound is involved in a wide range of plant-fungus interactions) might be
      modified on niche-specific manner in these phylogenetically related Fusarium
      species depending on their pathogenic strategy. Supporting the increased hydrogen
      peroxide sensitivity of F. graminearum, genome-wide analysis of stress signal
      transduction pathways revealed the absence one CatC-type catalase gene in F.
      graminearum in comparison to the other two species. 

PMID- 24939688
TI  - Whole genome sequence of a goose haemorrhagic polyomavirus detected in Hungary.
AB  - Goose haemorrhagic polyomavirus (GHPV) provoke haemorrhagic nephritis and
      enteritis of domestic geese. Outbreaks were detected in European countries and
      caused economic losses for goose keepers. Domestic ducks may be infected with
      GHPV without any signs typical for geese. The genomic organisation of some
      isolates was described but the gene functions and the pathomechanisms of the
      virus was not precisely defined. Here we describe the genome sequence and
      structure of GHPV of a goose from a Hungarian goose flock showing characteristics
      of the haemorrhagic nephritis and enteritis. The GHPV genome investigated in this
      study was 5252 bp long and was very similar (99% nucleotide identity) to
      sequences deposited in the GenBank. All the whole GHPV genomes possess the same
      ORFs in length, including the VP1, VP2, VP3, ORF-X, t and T tumour antigens.
      Amino acid changes are detected mainly in the putative ORF-X region. Data about
      the GHPV genome imply a conserved genomic structure among isolates from different
      countries. Genomic and epidemiological studies may help vaccine development
      efforts and identify potential heterologous reservoirs of GHPV. 

PMID- 24939689
TI  - Anti-chlamydial effect of plant peptides.
AB  - Even in asymptomatic cases of Chlamydia trachomatis infection, the aim of the
      antibiotic strategy is eradication of the pathogen so as to avoid the severe late
      sequelae, such as pelvic inflammatory disease, ectopic pregnancy, and tubal
      infertility. Although first-line antimicrobial agents have been demonstrated to
      be predominantly successful in the treatment of C. trachomatis infection,
      treatment failures have been observed in some cases. Rich source of antimicrobial
      peptides was recently discovered in Medicago species, which act in plants as
      differentiation factors of the endosymbiotic bacterium partner. Several of these
      symbiotic plant peptides have proved to be potent killers of various bacteria in
      vitro. We show here that 7 of 11 peptides tested exhibited antimicrobial activity
      against C. trachomatis D, and that the killing activity of these peptides is most
      likely due to their interaction with specific bacterial targets. 

PMID- 24939690
TI  - [The importance of vascular risk in type 2 diabetes mellitus].

PMID- 24939691
TI  - Measuring spatial correlations of photon pairs by automated raster scanning with
      spatial light modulators.
AB  - We demonstrate the use of a phase-only spatial light modulator for the
      measurement of transverse spatial distributions of coincidence counts between
      twin photon beams, in a fully automated fashion. This is accomplished by means of
      the polarization dependence of the modulator, which allows the conversion of a
      phase pattern into an amplitude pattern. We also present a correction procedure,
      that accounts for unwanted coincidence counts due to polarization decoherence
      effects. 

PMID- 24939692
TI  - Exceptionally abundant exceptions: comprehensive characterization of intrinsic
      disorder in all domains of life.
AB  - Recent years witnessed increased interest in intrinsically disordered proteins
      and regions. These proteins and regions are abundant and possess unique
      structural features and a broad functional repertoire that complements ordered
      proteins. However, modern studies on the abundance and functions of intrinsically
      disordered proteins and regions are relatively limited in size and scope of their
      analysis. To fill this gap, we performed a broad and detailed computational
      analysis of over 6 million proteins from 59 archaea, 471 bacterial, 110
      eukaryotic and 325 viral proteomes. We used arguably more accurate consensus
      based disorder predictions, and for the first time comprehensively characterized
      intrinsic disorder at proteomic and protein levels from all significant
      perspectives, including abundance, cellular localization, functional roles,
      evolution, and impact on structural coverage. We show that intrinsic disorder is
      more abundant and has a unique profile in eukaryotes. We map disorder into
      archaea, bacterial and eukaryotic cells, and demonstrate that it is
      preferentially located in some cellular compartments. Functional analysis that
      considers over 1,200 annotations shows that certain functions are exclusively
      implemented by intrinsically disordered proteins and regions, and that some of
      them are specific to certain domains of life. We reveal that disordered regions
      are often targets for various post-translational modifications, but primarily in
      the eukaryotes and viruses. Using a phylogenetic tree for 14 eukaryotic and 112
      bacterial species, we analyzed relations between disorder, sequence conservation
      and evolutionary speed. We provide a complete analysis that clearly shows that
      intrinsic disorder is exceptionally and uniquely abundant in each domain of life.

PMID- 24939693
TI  - Thioredoxin-interacting protein: a novel target for neuroprotection in
      experimental thromboembolic stroke in mice.
AB  - Redox imbalance in the brain significantly contributes to ischemic stroke
      pathogenesis, but antioxidant therapies have failed in clinical trials.
      Activation of endogenous defense mechanisms may provide better protection against
      stroke-induced oxidative injury. TXNIP (thioredoxin-interacting protein) is an
      endogenous inhibitor of thioredoxin (TRX), a key antioxidant system. We
      hypothesize that TXNIP inhibition attenuates redox imbalance and inflammation and
      provides protection against a clinically relevant model of embolic stroke. Male
      TXNIP-knockout (TKO), wild-type (WT), and WT mice treated with a pharmacological
      inhibitor of TXNIP, resveratrol (RES; 5 mg/kg body weight), were subjected to
      embolic middle cerebral artery occlusion (eMCAO). Behavior outcomes were
      monitored using neurological deficits score and grip strength meter at 24 h after
      eMCAO. Expression of oxidative, inflammatory, and apoptotic markers was analyzed
      by Western blot, immunohistochemistry, and slot blot at 24 h post-eMCAO. Our
      result showed that ischemic injury increases TXNIP in WT mice and that RES
      inhibits TXNIP expression and protects the brain against ischemic damage. TKO and
      RES-treated mice exhibited a 39.26 and 41.11 % decrease in infarct size and
      improved neurological score and grip strength compared to WT mice after eMCAO.
      Furthermore, the levels of TRX, nitrotyrosine, NOD-like receptor protein (NLRP3),
      interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and
      activations of caspase-1, caspase-3, and poly-ADP-ribose polymerase (PARP) were
      significantly (P < 0.05) attenuated in TKO and RES-treated mice. The present
      study suggests that TXNIP is contributing to acute ischemic stroke through redox
      imbalance and inflammasome activation and inhibition of TXNIP may provide a new
      target for therapeutic interventions. This study also affirms the importance of
      the antioxidant effect of RES on the TRX/TXNIP system.

PMID- 24939694
TI  - Carnosine exerts neuroprotective effect against 6-hydroxydopamine toxicity in
      hemiparkinsonian rat.
AB  - Parkinson's disease (PD) is the second most common disorder of the central
      nervous system due to the degeneration of mesencephalic dopaminergic neurons.
      Current treatments for PD have a symptomatic relief strategy with no prevention
      of disease progression. Due to the neuroprotective and antiapoptotic potential of
      the natural dipeptide carnosine, this study was conducted to assess its
      beneficial effect in 6-hydroxydopamine (6-OHDA)-induced model of PD in rat.
      Unilateral intrastriatal 6-OHDA-lesioned rats received i.p. carnosine at a dose
      of 250 mg/kg twice at an interval of 24 h, which started presurgery. Apomorphine
      caused contralateral rotations, a significant reduction in the number of Nissl
      stained neurons on the left side of the substantia nigra, and increased apoptosis
      was observed with enhanced oxidative stress burden in 6-OHDA-lesioned rats.
      Carnosine pretreatment significantly reduced rotations, attenuated apoptosis, and
      restored malondialdehyde and nitrite content and catalase activity with no
      significant effect on reduced glutathione (GSH). These results indicate that
      prelesion administration of carnosine could exert neuroprotection against 6-OHDA
      toxicity, and this may be of benefit in patients with early PD. 

PMID- 24939696
TI  - Following OGD/R, annexin 1 nuclear translocation and subsequent induction of
      apoptosis in neurons are assisted by myosin IIA in a TRPM7 kinase-dependent
      manner.
AB  - Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a
      bifunctional channel protein that contains an alpha-kinase domain at its C
      terminal. Previous studies have indicated that oxygen-glucose
      deprivation/reoxygenation (OGD/R) induces neuronal apoptosis via TRPM7. Annexin 1
      and myosin IIA have been identified as TRPM7 kinase substrates; however, the role
      of annexin 1 in OGD/R-induced neuron apoptosis remains unclear. Here, we report
      that OGD/R induces nuclear translocation of annexin 1 in primary cultured
      neurons. Interestingly, ablation of the TRPM7 kinase or a point mutation in
      Ser(5) interferes with TRPM7 kinase-annexin 1 binding, decreasing annexin 1
      nuclear translocation, and thereby reducing neuronal apoptosis. Furthermore,
      mutation of Arg(205), which intercepts annexin 1-formyl peptide receptor binding,
      also decreased annexin 1 nuclear translocation. Coimmunoprecipitation indicated
      that annexin 1 is moved as cargo through the cytoplasm by myosin IIA. However,
      inhibiting myosin IIA can decrease annexin 1 nuclear translocation. Moreover,
      blocking myosin IIA function by antagonist injection into the lateral ventricle
      was found to improve learning and memory in rats after middle cerebral artery
      occlusion and could also improve cell viability after OGD/R. Last, we determined
      that the annexin 1-myosin IIA complex is recognized and translocated by the
      importin alpha/beta heterodimer. Therefore, TRPM7 kinase modulates OGD/R-induced
      neuronal apoptosis via annexin 1 carried by myosin IIA, while nuclear formyl
      peptide receptor (FPR)-annexin 1 binding and importin beta are involved in
      nuclear translocation.

PMID- 24939698
TI  - [Usefulness of preoperative plasmapheresis in patients with thyrotoxicosis].

PMID- 24939697
TI  - The effects of stress on glutamatergic transmission in the brain.
AB  - Stress leads to detrimental effects on brain functions and results in various
      diseases. Recent studies highlight the involvement of glutamatergic transmission
      in pathogenesis of depressive behaviors and fears. Acute stress generates
      different impacts on the excitatory transmission compared to chronic stress.
      Different neuromodulators and epigenetic factors also participate in the
      alteration of synaptic transmission and the regulation of synaptic plasticity.
      Restoration of the glutamatergic transmission in stress-affected brain areas
      therefore provides novel directions of therapeutic interventions against stress. 

PMID- 24939699
TI  - [Intrapericardical paraganglioma associated with mutation in succinate
      dehydrogenase enzyme gene].

PMID- 24939695
TI  - Transcriptional and epigenetic substrates of methamphetamine addiction and
      withdrawal: evidence from a long-access self-administration model in the rat.
AB  - Methamphetamine use disorder is a chronic neuropsychiatric disorder characterized
      by recurrent binge episodes, intervals of abstinence, and relapses to drug use.
      Humans addicted to methamphetamine experience various degrees of cognitive
      deficits and other neurological abnormalities that complicate their activities of
      daily living and their participation in treatment programs. Importantly, models
      of methamphetamine addiction in rodents have shown that animals will readily
      learn to give themselves methamphetamine. Rats also accelerate their intake over
      time. Microarray studies have also shown that methamphetamine taking is
      associated with major transcriptional changes in the striatum measured within a
      short or longer time after cessation of drug taking. After a 2-h withdrawal time,
      there was increased expression of genes that participate in transcription
      regulation. These included cyclic AMP response element binding (CREB), ETS domain
      containing protein (ELK1), and members of the FOS family of transcription
      factors. Other genes of interest include brain-derived neurotrophic factor
      (BDNF), tyrosine kinase receptor, type 2 (TrkB), and synaptophysin.
      Methamphetamine-induced transcription was found to be regulated via
      phosphorylated CREB-dependent events. After a 30-day withdrawal from
      methamphetamine self-administration, however, there was mostly decreased
      expression of transcription factors including junD. There was also downregulation
      of genes whose protein products are constituents of chromatin-remodeling
      complexes. Altogether, these genome-wide results show that methamphetamine abuse
      might be associated with altered regulation of a diversity of gene networks that
      impact cellular and synaptic functions. These transcriptional changes might serve
      as triggers for the neuropsychiatric presentations of humans who abuse this drug.
      Better understanding of the way that gene products interact to cause
      methamphetamine addiction will help to develop better pharmacological treatment
      of methamphetamine addicts.

PMID- 24939700
TI  - Hydrogen sulfide inhibits Na+ uptake in larval zebrafish, Danio rerio.
AB  - The present study investigated the role of hydrogen sulfide (H2S) in regulating
      Na(+) uptake in larval zebrafish, Danio rerio. Waterborne treatment of larvae at
      4 days post-fertilization (dpf) with Na2S or GYY-4137 (chemicals known to
      generate H2S) significantly reduced Na(+) uptake. Exposure of larvae to water
      enriched with NaCl (1 mM NaCl) caused a pronounced reduction in Na(+) uptake
      which was prevented by pharmacological inhibition of cystathionine beta-synthase
      (CBS) or cystathionine gamma-lyase (CSE), two key enzymes involved in the
      endogenous synthesis of H2S. Furthermore, translational gene knockdown of CSE and
      CBSb significantly increased the basal rate of Na(+) uptake. Waterborne treatment
      with Na2S significantly decreased whole-body acid excretion and reduced Na(+)
      uptake in larval zebrafish preexposed to acidic (pH 4.0) water (a condition shown
      to promote Na(+) uptake via Na(+)-H(+)-exchanger 3b, NHE3b). However, Na2S did
      not affect Na(+) uptake in larvae depleted of NHE3b-containing ionocytes (HR
      cells) after knockdown of transcription factor glial cell missing 2 (gcm2) in
      which Na(+) uptake occurs predominantly via Na(+)-Cl(-) co-transporter (NCC)
      containing cells. These observations suggest that Na(+) uptake via NHE3b, but not
      NCC, is regulated by H2S. Whole-mount immunohistochemistry demonstrated that
      ionocytes expressing NHE3b also express CSE. These data suggests a
      physiologically relevant role of H2S as a mechanism to lower Na(+) uptake in
      zebrafish larvae, probably through its inhibitory action on NHE3b.

PMID- 24939702
TI  - MicroRNA-26a inhibits cell proliferation and invasion of cervical cancer cells by
      targeting protein tyrosine phosphatase type IVA 1.
AB  - The downregulation of microRNA-26a (miR-26a) has been reported in numerous types
      of cancer, but its detailed functional role in cervical cancer is not yet clear.
      In the present study, the expression of miR-26a in human cervical cancer was
      confirmed and its contribution to cervical cancer progression was investigated.
      The expression of miR-26a was determined by reverse transcription quantitative
      polymerase chain reaction in human cervical tissues and cell lines. Cell growth
      and invasion were detected by cell counting kit-8, colony-forming assays and
      transwell assays following restoration of miR-26a expression. Protein tyrosine
      phosphatase type IVA 1 (PRL-1) was further validated as a target of miR-26a by a
      functional luciferase assay and western blot analysis. In addition, the
      overexpression of miR-26a in tumor formation in SCID mice was investigated in
      vivo, and the association between miR-26a and PRL-1 was assayed by Pearson's
      correlation coefficient. First, it was identified that miR-26a was significantly
      downregulated in cervical cancer compared with the paired adjacent tissues.
      Forced expression of miR-26a suppressed cell proliferation and invasion in vitro
      and inhibited the growth of tumor xenografts in vivo. PRL-1 was determined as a
      novel target for miR-26a and knockdown of PRL-1 partially phenocopied the effect
      of miR-26a restoration. In addition, PRL-1 expression was inversely correlated
      with miR-26a expression in cervical cancer tissues. In conclusion, the results
      demonstrated the role of miR-26a in cervical cancer pathogenesis and suggest it
      may be used as a potential novel therapeutic strategy for cervical cancer.

PMID- 24939703
TI  - Strong subjective recovery as a protective factor against the effects of positive
      symptoms on quality of life outcomes in schizophrenia.
AB  - BACKGROUND: Interest in recovery from schizophrenia has been growing steadily,
      with much of the focus on remission from psychotic symptoms and a return to
      functioning. Less is known about the experience of subjective recovery and its
      relationships with other important outcomes, such as quality of life and the
      formation and sustenance of social connections. This study sought to address this
      gap in knowledge by examining the links between self perceived recovery,
      symptoms, and the social components of quality of life. METHODS: Sixty eight
      veterans with schizophrenia-spectrum disorders who were participating in a study
      of cognitive remediation and work were concurrently administered the Recovery
      Assessment Scale, Positive and Negative Syndrome Scale, and the Heinrichs
      Carpenter Quality of Life Scale (QLS). RESULTS: Linear regression analyses
      demonstrated that subjective recovery moderated the relationship between positive
      symptoms and both QLS intrapsychic foundations scores and QLS instrumental role
      functioning after controlling for negative symptoms. Further examination of this
      interaction revealed that for individuals with substantial positive symptoms,
      higher levels of subjective recovery were associated with better instrumental
      role functioning and intrapsychic foundational abilities. CONCLUSION: Greater
      self perceived recovery is linked with stronger quality of life, both in regards
      to the cognitive and affective bases for socialization and active community
      involvement, even in the presence of substantial psychotic symptoms. Clinical
      implications of these findings are discussed.

PMID- 24939701
TI  - Odontoblasts as sensory receptors: transient receptor potential channels,
      pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron
      signal transduction.
AB  - Various stimuli induce pain when applied to the surface of exposed dentin.
      However, the mechanisms underlying dentinal pain remain unclear. We investigated
      intercellular signal transduction between odontoblasts and trigeminal ganglion
      (TG) neurons following direct mechanical stimulation of odontoblasts. Mechanical
      stimulation of single odontoblasts increased the intracellular free calcium
      concentration ([Ca(2+)]i) by activating the mechanosensitive-transient receptor
      potential (TRP) channels TRPV1, TRPV2, TRPV4, and TRPA1, but not TRPM8 channels.
      In cocultures of odontoblasts and TG neurons, increases in [Ca(2+)]i were
      observed not only in mechanically stimulated odontoblasts, but also in
      neighboring odontoblasts and TG neurons. These increases in [Ca(2+)]i were
      abolished in the absence of extracellular Ca(2+) and in the presence of
      mechanosensitive TRP channel antagonists. A pannexin-1 (ATP-permeable channel)
      inhibitor and ATP-degrading enzyme abolished the increases in [Ca(2+)]i in
      neighboring odontoblasts and TG neurons, but not in the stimulated odontoblasts.
      G-protein-coupled P2Y nucleotide receptor antagonists also inhibited the
      increases in [Ca(2+)]i. An ionotropic ATP (P2X3) receptor antagonist inhibited
      the increase in [Ca(2+)]i in neighboring TG neurons, but not in stimulated or
      neighboring odontoblasts. During mechanical stimulation of single odontoblasts, a
      connexin-43 blocker did not have any effects on the [Ca(2+)]i responses observed
      in any of the cells. These results indicate that ATP, released from mechanically
      stimulated odontoblasts via pannexin-1 in response to TRP channel activation,
      transmits a signal to P2X3 receptors on TG neurons. We suggest that odontoblasts
      are sensory receptor cells and that ATP released from odontoblasts functions as a
      neurotransmitter in the sensory transduction sequence for dentinal pain. 

PMID- 24939704
TI  - The exacerbation of depression, hostility, and social anxiety in the course of
      Internet addiction among adolescents: a prospective study.
AB  - BACKGROUND: In adolescent populations worldwide, Internet addiction is prevalent
      and is often comorbid with depression, hostility, and social anxiety of
      adolescents. This study aimed at evaluating the exacerbation of depression,
      hostility, and social anxiety in the course of getting addiction to Internet or
      remitting from Internet addiction among adolescents. METHOD: This study recruited
      2293 adolescents in grade 7 to assess their depression, hostility, social anxiety
      and Internet addiction. The same assessments were repeated one year later. The
      incidence group was defined as subjects classified as non-addicted in the first
      assessment and as addicted in the second assessment. The remission group was
      defined as subjects classified as addicted in the first assessment and as non
      addicted in the second assessment. RESULTS: The incidence group exhibited
      increased depression and hostility more than the non-addiction group and the
      effect of on depression was stronger among adolescent girls. Further, the
      remission group showed decreased depression, hostility, and social anxiety more
      than the persistent addiction group. CONCLUSIONS: Depression and hostility worsen
      in the addiction process for the Internet among adolescents. Intervention of
      Internet addiction should be provided to prevent its negative effect on mental
      health. Depression, hostility, and social anxiety decreased in the process of
      remission. It suggested that the negative consequences could be reversed if
      Internet addiction could be remitted within a short duration.

PMID- 24939705
TI  - Mediating effects of depression and anxiety on the relationship between bullying
      involvement and pain problems among adolescents in Taiwan.
AB  - BACKGROUND: This study aimed to examine the mediating effects of depression and
      anxiety on the relationships of bullying victimization and perpetration with pain
      among adolescents in Taiwan. METHOD: A total of 4976 students of junior and
      senior high schools completed the questionnaires. Bullying victimization and
      perpetration, pain problems, depression, and anxiety were assessed. The mediating
      effects of depression and anxiety on the relationship between bullying
      involvement and pain problems and the moderating effects of sex on the medicating
      roles of depression and anxiety were examined by structural equation model.
      RESULTS: Both depression and anxiety were significant mediators of the
      relationship between bullying victimization and pain problems among adolescents.
      Depression was also a significant mediator of the relationship between bullying
      perpetration and pain problems among adolescents. Sex had no moderating effect on
      the mediating role of depression/anxiety on the association between bullying
      involvement and pain problems. CONCLUSIONS: Medical and educational professionals
      should survey and intervene in depression and anxiety when managing pain problems
      among adolescents involved in bullying.

PMID- 24939706
TI  - Evaluation of antiretroviral treatment programme monitoring in Eastern Cape,
      South Africa.
AB  - INTRODUCTION: The provision of antiretroviral treatment (ART) for HIV infection
      is a key strategy in addressing the high burden of HIV/AIDS in South Africa and
      improving the quality and length of life for those infected. Information produced
      from routine monitoring is essential for evidence-based decision-making within
      ART programmes. An evaluation of the ART programme data system in Eastern Cape,
      South Africa was conducted to determine the causes of irregular reporting and to
      make recommendations to improve data quality. METHODS: Data audits and semi
      structured interviews were performed in facilities that initiate and provide ART.
      Thirty-two facilities in three sub-districts were audited. RESULTS: The number of
      adults receiving ART was over-reported by 36.6% (P < 0.05) on the District Health
      Information System. The interviews of nurses and administrators revealed various
      factors that contributed to the inaccuracy of the data including training,
      staffing levels, use of registers, data verification processes, and
      standardization with programme partners. CONCLUSIONS: Recommendations to address
      the inaccuracy of ART programme data include improving knowledge translation
      during training of ART programme staff, ensuring the implementation of
      established data verification policies and procedures, rethinking the design of
      the programme to reduce the burden on health facilities and personnel, and
      standardizing information management procedures amongst the various governmental
      and non-governmental stakeholders. The challenges with reporting in the Eastern
      Cape may be shared by other South African provinces as well as other low-middle
      income countries that require high quality data to inform well-designed and well
      implemented interventions in the fight against HIV/AIDS.

PMID- 24939708
TI  - Histology of the ovary of Chinchilla lanigera in captivity.
AB  - Chinchilla, the lanigera variety in particular, is one of the most valuable
      rodents in the fur industry. The chinchilla ovary is morphologically similar to
      that of other South American hystricognath rodents, especially as regards its
      anatomy and, to a lesser degree, its histology. The presence of numerous primary
      follicles throughout the annual cycle suggests that a few of them are recruited
      to initiate growth and differentiation during folliculogenesis. Primary follicles
      with two or more oocytes are common; this is not the case with follicles at more
      advanced stages, suggesting that they do not develop. Only one or two large
      corpora lutea (CL) and three to five small or accessories CL were observed but no
      corpora albicans. The presence of accessory CL may reflect the importance of
      continuous hormonal production to support prolonged gestation. Atretic CL were
      also present, showing signs of degeneration in luteal cells. The interstitial
      cells distributed throughout the cortex were the main histological feature shared
      with other species, as stated in previous reports. Antral atresia was observed in
      all sizes of antral follicles while basal atresia was confined exclusively to
      smaller follicles. 

PMID- 24939707
TI  - Structural characterization and subcellular localization of Drosophila organic
      solute carrier partner 1.
AB  - BACKGROUND: Organic solute carrier partner 1 (OSCP1) is known to facilitate the
      transport of various organic solutes into cells and reported to play a role in
      cell growth and cell differentiation. Moreover, OSCP1 is known as a tumor
      suppressor gene that is frequently down-expressed in nasopharyngeal carcinomas
      and acute myeloid leukemia. However, the underlying mechanisms of action remain
      unclear and the subcellular localization of OSCP1 has yet to be determined in
      detail. RESULTS: Drosophila contains a single orthologue of OSCP1 (dOSCP1) that
      shares 58% homology with its human counterpart. To study the expression pattern
      and subcellular localization of dOSCP1, we prepared a specific antibody.
      Subcellular localization analyses of dOSCP1 with these revealed localization in
      the plasma membrane, endoplasmic reticulum, Golgi apparatus and mitochondria, but
      no detection in cytosol. dOSCP1 signals were also detected in the nucleus,
      although at weaker intensity than in plasma membranes and subcellular organelles.
      In addition, native polyacrylamide gel electrophoresis analysis with and without
      beta-mercaptoethanol treatment revealed that recombinant dOSCP1 forms dimers and
      trimers in solution. The dimer form of dOSCP1 could also be detected by Western
      immunoblot analyses in third instar larval extracts. CONCLUSIONS: The data
      revealed that dOSCP1 localizes not only in the plasma membrane but also in the
      nucleus, ER, Golgi apparatus and mitochondria. It is therefore conceivable that
      this protein may interact with various partners or form multimeric complexes with
      other proteins to play multiple roles in cells, providing clues to understanding
      the functions of dOSCP1 during Drosophila development.

PMID- 24939709
TI  - Mechanical vibrations of magnetically levitated viscoelastic droplets.
AB  - The mechanical vibrations of magnetically levitated droplets were investigated
      using a simple optical deflection technique. Droplets of water and a water-based
      solution of poly(acrylamide-co-acrylic acid) were levitated in the bore of a
      superconducting magnet and perturbed with a short puff of air. Centre of mass and
      surface vibrations were monitored using laser light refracted through the
      droplet, focussed on to the end of an optical fiber and detected using a
      photodiode. Time dependent variations in the voltage generated by the photodiode
      were Fourier transformed to obtain the frequency and spectral width of the drops'
      mechanical resonances. A simple theory of drop vibration was developed to extract
      the rheological properties of the droplets from these quantities. The resulting
      values of G' and G'' that were extracted were found to be in good agreement with
      values obtained using conventional rheology techniques. 

PMID- 24939710
TI  - Odour emission characteristics of 22 recreational rivers in Nanjing.
AB  - The odour emission characteristics of 22 recreational rivers in Nanjing were
      investigated and analysed. Eight odorous compounds (ammonia (NH3), hydrogen
      sulphide (H2S), sulphur dioxide (SO2), carbon disulphide (CS2), nitrobenzene
      (C6H5NO2), aniline (C6H5NH2), dimethylamine (C2H7N), and formaldehyde (HCHO))
      were measured in odour emission samples collected using a custom-made emission
      flux hood chamber. The results showed that all odorants were detected in all
      monitoring rivers. NH3 was the main odorant, with emission rates ranging from
      4.86 to 15.13 MUg/min m(2). The total odour emission rate of the Nan River, at 1
      427.07 OU/s, was the highest of the all investigated rivers. H2S, NH3 and
      nitrobenzene were three key odour emission contributors according to their
      contributions to the total odour emission. A correlation analysis of the
      pollutants showed there was a significant positive correlation between the
      emission rate of NH3 and the concentration of ammonia nitrogen (NH4 (+)-N) and
      total nitrogen (TN). The H2S and SO2 emission rates had a significant positive
      correlation with sulphides (S(2-)) and available sulphur (AS) in the water and
      sediment. The content of TN, NH4(+)-N, S(2-) and AS in the water and sediment
      affected the concentration of H2S, SO2 and NH3 in the emission gases. NH4(+)-N,
      S(2-) and AS are suggested as the key odour control indexes for reducing odours
      emitted from these recreational rivers. The study provides useful information for
      effective pollution control, especially for odour emission control for the
      recreational rivers of the city. It also provides a demonstrate example to show
      how to monitor and assess a contaminated river when odour emission and its
      control need to be focused on.

PMID- 24939711
TI  - Submicron particle characteristics of atmospheres in a long highway tunnel.
AB  - This study used a scanning mobility particle sizer (SMPS) to measure and
      categorize submicron atmospheric particles in the 14-737-nm size range for
      ambient and urban roadside air and for air in the Hsuehshan Tunnel (12.9 km),
      Taiwan. Principal component analysis, traffic flow, and particle size
      distributions were used to identify the emission characteristics of light-duty
      vehicles (LDV) with the SMPS data. In the Hsuehshan Tunnel, the particle size
      from the majority of emissions discharged by LDV is approximately 20-60 nm, and
      the maximum particle number can reach up to 2.5 * 10(5). In contrast, submicron
      particle size distribution for urban roadsides is mostly 14-200 nm, and the
      maximum particle number is approximately 4 * 10(4) with the particle number for
      most particle sizes being below 1,200. The submicron particle size distribution
      at the ambient air station was unimodal with a mode sizes at 30-50 nm with the
      maximum particle number of 3,000.

PMID- 24939712
TI  - Neuropsychiatric disorders and potentially preventable hospitalizations in a
      prospective cohort study of older Americans.
AB  - BACKGROUND: The relative contributions of depression, cognitive impairment
      without dementia (CIND), and dementia to the risk of potentially preventable
      hospitalizations in older adults are not well understood. OBJECTIVE(S): To
      determine if depression, CIND, and/or dementia are each independently associated
      with hospitalizations for ambulatory care-sensitive conditions (ACSCs) and
      rehospitalizations within 30 days after hospitalization for pneumonia, congestive
      heart failure (CHF), or myocardial infarction (MI). DESIGN: Prospective cohort
      study. PARTICIPANTS: Population-based sample of 7,031 Americans > 50 years old
      participating in the Health and Retirement Study (1998-2008). MAIN MEASURES: The
      eight-item Center for Epidemiologic Studies Depression Scale and/or International
      Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM)
      depression diagnoses were used to identify baseline depression. The Modified
      Telephone Interview for Cognitive Status and/or ICD-9-CM dementia diagnoses were
      used to identify baseline CIND or dementia. Primary outcomes were time to
      hospitalization for an ACSC and presence of a hospitalization within 30 days
      after hospitalization for pneumonia, CHF, or MI. KEY RESULTS: All five categories
      of baseline neuropsychiatric disorder status were independently associated with
      increased risk of hospitalization for an ACSC (depression alone: Hazard Ratio
      [HR]: 1.33, 95% Confidence Interval [95%CI]: 1.18, 1.52; CIND alone: HR: 1.25,
      95%CI: 1.10, 1.41; dementia alone: HR: 1.32, 95%CI: 1.12, 1.55; comorbid
      depression and CIND: HR: 1.43, 95%CI: 1.20, 1.69; comorbid depression and
      dementia: HR: 1.66, 95%CI: 1.38, 2.00). Depression (Odds Ratio [OR]: 1.37, 95%CI:
      1.01, 1.84), comorbid depression and CIND (OR: 1.98, 95%CI: 1.40, 2.81), or
      comorbid depression and dementia (OR: 1.58, 95%CI: 1.06, 2.35) were independently
      associated with increased odds of rehospitalization within 30 days after
      hospitalization for pneumonia, CHF, or MI. CONCLUSIONS: Depression, CIND, and
      dementia are each independently associated with potentially preventable
      hospitalizations in older Americans. Older adults with comorbid depression and
      cognitive impairment represent a particularly at-risk group that could benefit
      from targeted interventions.

PMID- 24939713
TI  - The specification of imprints in mammals.
AB  - At the heart of genomic imprinting in mammals are imprinting control regions
      (ICRs), which are the discrete genetic elements that confer imprinted monoallelic
      expression to several genes in imprinted gene clusters. A characteristic of the
      known ICRs is that they acquire different epigenetic states, exemplified by
      differences in DNA methylation, in the sperm and egg, and these imprint marks
      remain on the sperm- and oocyte-derived alleles into the next generation as a
      lifelong memory of parental origin. Although there has been much focus on gametic
      marking of ICRs as the point of imprint specification, recent mechanistic studies
      and genome-wide DNA methylation profiling do not support the existence of a
      specific imprinting machinery in germ cells. Rather, ICRs are part of more
      widespread methylation events that occur during gametogenesis. Instead, a
      decisive component in the specification of imprints is the choice of which sites
      of gamete-derived methylation to maintain in the zygote and preimplantation
      embryo at a time when much of the remainder of the genome is being demethylated.
      Among the factors involved in this selection, the zinc-finger protein Zfp57 can
      be regarded as an imprint-specific, sequence-specific DNA binding factor
      responsible for maintaining methylation at most ICRs. The recent insights into
      the balance of gametic and zygotic contributions to imprint specification should
      help understand mechanistic opportunities and constraints on the evolution of
      imprinting in mammals. 

PMID- 24939714
TI  - Suppression of PAX6 promotes cell proliferation and inhibits apoptosis in human
      retinoblastoma cells.
AB  - The aim of this study was to investigate the role of the transcription factor,
      PAX6, in the development of retinoblastoma. The expression of endogenous PAX6 was
      knocked down using PAX6-specific lentivirus in two human retinoblastoma cell
      lines, SO-Rb50 and Y79. Cell proliferation functional assays and apoptotic assays
      were performed on the cells in which PAX6 was knocked down. The results revealed
      that PAX6 knockdown efficiency was significant (P<0.01, n=3) in the SO-Rb50 and
      Y79 cells. The inhibition of PAX6 reduced tumor cell apoptosis (P<0.05, n=3), but
      induced cell cycle S phase arrest (SO-Rb50; P<0.05, n=3) and G2/M phase arrest
      (Y79; P<0.05, n=3). Western blot analysis indicated that the inhibition of PAX6
      increased the levels of the anti-apoptotic proteins, Bcl-2, proliferating cell
      nuclear antigen (PCNA) and CDK1, but reduced the levels of the pro-apoptotic
      proteins, BAX and p21. In conclusion, our data demonstrate that the suppression
      of PAX6 increases proliferation and decreases apoptosis in human retinoblastoma
      cells by regulating several cell cycle and apoptosis biomarkers.

PMID- 24939715
TI  - [Principles of treatment of spastic palsy in children: a critical review].
AB  - BACKGROUND: In patients with cerebral palsy who are able to walk the source of
      the problem of spasticity must first be correctly determined. The weakness
      appears to be the main problem and the first line treatment must concentrate on
      improvement of strength and bodily control. THERAPY: Spasticity can also
      compensate for weaknesses. The indications for weakening measures for correction
      of muscle tonus must therefore be carefully appraised but are part of the
      repertoire. Orthoses result in stability and correction of deformities. Night
      braces are in our experience of doubtful value. Biomechanical objectives are a
      right-angle between the sole of the shoe and lower leg axis (leading edge of the
      tibia) and full passive and active extension in the knees and hips. CONCLUSION:
      Severely handicapped patients often suffer from hip luxation and scoliosis.
      Regular control of the hips and spine under loading are necessary. Early
      interventions, conservative and operative, have a better prognosis than a late
      correction. In general patients who have a risk for deformities and dysfunction
      of the musculoskeletal system due to the underlying disease should undergo early
      orthopedic control.

PMID- 24939716
TI  - Isolating plasma from blood using a dielectrophoresis-active hydrophoretic
      device.
AB  - Plasma is a complex substance that contains proteins and circulating nucleic
      acids and viruses that can be utilised for clinical diagnostics, albeit a precise
      analysis depends on the plasma being totally free of cells. We proposed the use
      of a dielectrophoresis (DEP)-active hydrophoretic method to isolate plasma from
      blood in a high-throughput manner. This microfluidic device consists of
      anisotropic microstructures embedded on the top of the channel which generate
      lateral pressure gradients while interdigitised electrodes lay on the bottom of
      the channel which can push particles or cells into a higher level using a
      negative DEP force. Large and small particles or cells (3 MUm and 10 MUm
      particles, and red blood cells, white blood cells, and platelets) can be focused
      at the same time in our DEP-active hydrophoretic device at an appropriate flow
      rate and applied voltage. Based on this principle, all the blood cells were
      filtrated from whole blood and then the plasma was extracted with a purity of
      94.2% and a yield of 16.5% at a flow rate of 10 MUL min(-1). This solved the
      challenging problem caused by the relatively low throughput of the DEP based
      device. Our DEP-active hydrophoretic device is a flexible and tunable system that
      can control the lateral positions of particles by modulating the external
      voltages without redesigning and fabricating a new channel, and because it is
      easy to operate, it is easily compatible with other microfluidic platforms that
      are used for further detection. 

PMID- 24939717
TI  - Genome-wide analysis of simple sequence repeats in marine animals-a comparative
      approach.
AB  - Tandem simple sequence repeats (SSRs) are one of the most popular molecular
      markers in genetic analysis owing to their ubiquitous occurrence,high
      reproducibility, multiallelic nature, and codominant mode. High mutability makes
      SSRs play a role in genome evolution and correspondingly show different patterns.
      Comparative analysis of genomic SSRs in different taxonomic groups usually
      focuses on land species, while marine animals have been neglected. This study
      examined the abundance of genomic SSRs with repeated unit lengths of 1-6 bp in 30
      marine animals including nine taxonomic groups and further compared with the land
      species. More than thousands of SSRs were discovered in every organism which
      provided a huge resource for the development of molecular markers. Thirty marine
      animals showed profound differences in SSR characteristics, but some group
      specific trends were also found. Both similarities and differences of repeat
      patterns were discovered between the land and marine species. Two taxon-specific
      SSR types were discovered: the pentanucleotides motif AGAGG in Euteleostei and
      the hexanucleotide repeats of ATGTAC in Porifera and Echinodermata. Gene ontology
      (GO) enrichment analysis of two representative species (Amphimedon queenslandica
      for Porifera and Strongylocentrotus purpuratus for Echinodermata) revealed
      functional preference of the ATGTAC motif associated genes, and this might hint
      at evolutionary significance.

PMID- 24939718
TI  - Immobilized growth of the peridinin-producing marine dinoflagellate Symbiodinium
      in a simple biofilm photobioreactor.
AB  - Products from phototrophic dinoflagellates such as toxins or pigments are
      potentially important for applications in the biomedical sciences, especially in
      drug development. However, the technical cultivation of these organisms is often
      problematic due to their sensitivity to hydrodynamic (shear) stress that is a
      characteristic of suspension-based closed photobioreactors (PBRs). It is thus
      often thought that most species of dinoflagellates are non-cultivable at a
      technical scale. Recent advances in the development of biofilm PBRs that rely on
      immobilization of microalgae may hold potential to circumvent this major
      technical problem in dinoflagellate cultivation. In the present study, the
      dinoflagellate Symbiodinium voratum was grown immobilized on a Twin-Layer PBR for
      isolation of the carotenoid peridinin, an anti-cancerogenic compound. Biomass
      productivities ranged from 1.0 to 11.0 g m(-2) day(-1) dry matter per vertical
      growth surface and a maximal biomass yield of 114.5 g m(-2), depending on light
      intensity, supplementary CO2, and type of substrate (paper or polycarbonate
      membrane) used. Compared to a suspension culture, the performance of the Twin
      Layer PBRs exhibited significantly higher growth rates and maximal biomass yield.
      In the Twin-Layer PBR a maximal peridinin productivity of 24 mg m(-2) day(-1) was
      determined at a light intensity of 74 MUmol m(-2) s(-1), although the highest
      peridinin content per dry weight (1.7 % w/w) was attained at lower light
      intensities. The results demonstrate that a biofilm-based PBR that minimizes
      hydrodynamic shear forces is applicable to technical-scale cultivation of
      dinoflagellates and may foster biotechnological applications of these abundant
      marine protists. 

PMID- 24939719
TI  - Denosumab for management of refractory hypercalcaemia in recurrent parathyroid
      carcinoma.

PMID- 24939720
TI  - Characterization and evaluation of triamcinolone, raloxifene, and their dual
      loaded microspheres as prospective local treatment system in rheumatic rat
      joints.
AB  - In this study, injectable microspheres were developed for the local treatment of
      joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with
      triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage
      regenerative drug, were prepared with a biodegradable and biocompatible polymer,
      polycaprolactone (PCL). Microspheres were optimized for particle size, structural
      properties, drug release, and loading properties. In vitro release of Ral was
      very slow because of the low solubility of the drug and hydrophobic nature of
      PCL. However, when coloaded with TA, both drugs were released at higher amounts
      compared with their single forms. Smallest particle sizes were obtained in dual
      drug-loaded microspheres. In vitro cytotoxicity tests showed biocompatibility of
      microspheres. In vivo bioefficacy of these microspheres was also examined in
      adjuvant-induced arthritis model in rats. In vivo histological studies of control
      groups showed development of RA with high median lesion score (5.0). Compared
      with control and intra-articular free drug injections, microsphere treatment
      groups showed lower lesion scores and better healing outcomes in histological
      evaluations. Results suggest that a controlled delivery system of TA and RAL by a
      single injection in inflamed joints holds promise for healing and suppressing
      inflammation.

PMID- 24939722
TI  - Small sample sorting of primary adherent cells by automated micropallet imaging
      and release.
AB  - Primary patient samples are the gold standard for molecular investigations of
      tumor biology yet are difficult to acquire, heterogeneous in nature and variable
      in size. Patient-derived xenografts (PDXs) comprised of primary tumor tissue
      cultured in host organisms such as nude mice permit the propagation of human
      tumor samples in an in vivo environment and closely mimic the phenotype and gene
      expression profile of the primary tumor. Although PDX models reduce the cost and
      complexity of acquiring sample tissue and permit repeated sampling of the primary
      tumor, these samples are typically contaminated by immune, blood, and vascular
      tissues from the host organism while also being limited in size. For very small
      tissue samples (on the order of 10(3) cells) purification by fluorescence
      activated cell sorting (FACS) is not feasible while magnetic activated cell
      sorting (MACS) of small samples results in very low purity, low yield, and poor
      viability. We developed a platform for imaging cytometry integrated with
      micropallet array technology to perform automated cell sorting on very small
      samples obtained from PDX models of pancreatic and colorectal cancer using
      antibody staining of EpCAM (CD326) as a selection criteria. These data
      demonstrate the ability to automate and efficiently separate samples with very
      low number of cells.

PMID- 24939723
TI  - Water-mediated proton conduction in a robust triazolyl phosphonate metal-organic
      framework with hydrophilic nanochannels.
AB  - The development of water-mediated proton-conducting materials operating above 100
      degrees C remains challenging because the extended structures of existing
      materials usually deteriorate at high temperatures. A new triazolyl phosphonate
      metal-organic framework (MOF) [La3L4(H2O)6]Cl?x H2O (1, L(2-) = 4-(4H-1,2,4
      triazol-4-yl)phenyl phosphonate) with highly hydrophilic 1D channels was
      synthesized hydrothermally. Compound 1 is an example of a phosphonate MOF with
      large regular pores with 1.9 nm in diameter. It forms a water-stable, porous
      structure that can be reversibly hydrated and dehydrated. The proton-conducting
      properties of 1 were investigated by impedance spectroscopy. Magic-angle spinning
      (MAS) and pulse field gradient (PFG) NMR spectroscopies confirm the dynamic
      nature of the incorporated water molecules. The diffusivities, determined by PFG
      NMR and IR microscopy, were found to be close to that of liquid water. This
      porous framework accomplishes the challenges of water stability and proton
      conduction even at 110  degrees C. The conductivity in 1 is proposed to occur by
      the vehicle mechanism.

PMID- 24939721
TI  - Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and
      fibrosis in male experimental rats.
AB  - The possible effectiveness of resveratrol, a polyphenol present in different
      plants comprising berries, grapes and peanuts, on the prevention of doxorubicin
      induced cardiac toxicity and fibrosis was investigated. Forty adult male Wistar
      albino rats were divided into four groups. Group I received normal saline, group
      II gavaged with resveratrol (20 mg/kg, daily for 4 weeks), group III received
      doxorubicin (2.5 mg/kg i.p. in six injections for 2 weeks; accumulative dose of
      15 mg/kg), and group IV received doxorubicin + resveratrol (starting resveratrol
      intake 2 weeks before doxorubicin administration). Resveratrol significantly
      alleviated the increase in left ventricular lipid peroxidation, hydroxyproline,
      and tumor necrosis factor alpha levels as well as serum creatine kinase
      myocardial band (CK-MB) activity and prevented the decrease in body and heart
      weights in doxorubicin-treated group. However, a marked protection against
      reduced glutathione content depletion and superoxide dismutase activity reduction
      was observed in the left ventricles of rats pretreated with resveratrol in
      combination with doxorubicin. Resveratrol also ameliorated the up-regulation of
      left ventricular caspase-3 and transforming growth factor-beta1 gene expression
      as well as left ventricular histopathological changes including necrosis and
      fibrosis induced by doxorubicin. Collectively, our results suggest that
      resveratrol provides a significant protection against doxorubicin-induced
      cardiotoxicity and fibrosis in rats. Therefore, it may be used as a promising
      cardioprotective agent in patients treated with doxorubicin due to malignant
      diseases. So, further clinical trials are required to confirm these findings.

PMID- 24939724
TI  - The presupplementary area within the language network: a resting state functional
      magnetic resonance imaging functional connectivity analysis.
AB  - The presupplementary motor area (pre-SMA) is involved in volitional selection.
      Despite the lateralization of the language network and different functions for
      both pre-SMA, few studies have reported the lateralization of pre-SMA activity
      and very little is known about the possible lateralization of pre-SMA
      connectivity. Via functional connectivity analysis, we sought to understand how
      the language network may be connected to other intrinsic connectivity networks
      (ICNs) through the pre-SMA. We performed a spatial independent component analysis
      of resting state functional magnetic resonance imaging in 30 volunteers to
      identify the language network. Subsequently, we applied seed-to-voxel functional
      connectivity analyses centered on peaks detected in the pre-SMA. Three signal
      peaks were detected in the pre-SMA. The left rostral pre-SMA intrinsic
      connectivity network (LR ICN) was left lateralized in contrast to bilateral ICNs
      associated to right pre-SMA peaks. The LR ICN was anticorrelated with the dorsal
      attention network and the right caudal pre-SMA ICN (RC ICN) anticorrelated with
      the default mode network. These two ICNs overlapped minimally. In contrast, the
      right rostral ICN overlapped the LR ICN. Both right ICNs overlapped in the
      ventral attention network (vATT). The bilateral connectivity of the right rostral
      pre-SMA may allow right hemispheric recruitment to process semantic ambiguities.
      Overlap between the right pre-SMA ICNs in vATT may contribute to internal thought
      to external environment reorientation. Distinct ICNs connected to areas involved
      in lexico-syntactic selection and phonology converge in the pre-SMA, which may
      constitute the resolution space of competing condition-action associations for
      speech production.

PMID- 24939725
TI  - Nature's chemical signatures in human olfaction: a foodborne perspective for
      future biotechnology.
AB  - The biocatalytic production of flavor naturals that determine chemosensory
      percepts of foods and beverages is an ever challenging target for academic and
      industrial research. Advances in chemical trace analysis and post-genomic
      progress at the chemistry-biology interface revealed odor qualities of nature's
      chemosensory entities to be defined by odorant-induced olfactory receptor
      activity patterns. Beyond traditional views, this review and meta-analysis now
      shows characteristic ratios of only about 3 to 40 genuine key odorants for each
      food, from a group of about 230 out of circa 10 000 food volatiles. This suggests
      the foodborn stimulus space has co-evolved with, and roughly match our circa 400
      olfactory receptors as best natural agonists. This perspective gives insight into
      nature's chemical signatures of smell, provides the chemical odor codes of more
      than 220 food samples, and beyond addresses industrial implications for producing
      recombinants that fully reconstruct the natural odor signatures for use in
      flavors and fragrances, fully immersive interactive virtual environments, or
      humanoid bioelectronic noses. 

PMID- 24939727
TI  - Viability analysis of fisheries management on hermaphrodite population.
AB  - We study the viability domains of bio-economic constraints for fishing model of
      hermaphrodite population, displaying three stages, juvenile, female and male. The
      dynamic of this model is subject to two constraints: an ecological constraint
      ensuring the stock perennity, and an economic constraint ensuring a minimum
      revenue for fishermen. Using viability kernel, we find out a viability domain
      which simultaneously guarantees a minimum stock level and a minimum income for
      fleets. 

PMID- 24939728
TI  - A modified k-TSP algorithm and its application in LC-MS-based metabolomics study
      of hepatocellular carcinoma and chronic liver diseases.
AB  - In systems biology, the ability to discern meaningful information that reflects
      the nature of related problems from large amounts of data has become a key issue.
      The classification method using top scoring pairs (TSP), which measures the
      features of a data set in pairs and selects the top ranked feature pairs to
      construct the classifier, has been a powerful tool in genomics data analysis
      because of its simplicity and interpretability. This study examined the
      relationship between two features, modified the ranking criteria of the k-TSP
      method to measure the discriminative ability of each feature pair more
      accurately, and correspondingly, provided an improved classification procedure.
      Tests on eight public data sets showed the validity of the modified method. This
      modified k-TSP method was applied to our serum metabolomics data derived from
      liquid chromatography-mass spectrometry analysis of hepatocellular carcinoma and
      chronic liver diseases. Based on the 27 selected feature pairs, HCC and chronic
      liver diseases were accurately distinguished using the principal component
      analysis, and certain profound metabolic disturbances related to liver disease
      development were revealed by the feature pairs. 

PMID- 24939729
TI  - Analysis of eicosanoids, amino acids, organic acids, and microRNAs.

PMID- 24939730
TI  - Menstrual blood-derived stromal stem cells from women with and without
      endometriosis reveal different phenotypic and functional characteristics.
AB  - Retrograde flow of menstrual blood cells during menstruation is considered as the
      dominant theory for the development of endometriosis. Moreover, current evidence
      suggests that endometrial-derived stem cells are key players in the pathogenesis
      of endometriosis. In particular, endometrial stromal stem cells have been
      suggested to be involved in the pathogenesis of this disease. Here, we aimed to
      use menstrual blood, as a novel source of endometrial stem cells, to investigate
      whether stromal stem cells from endometriosis (E-MenSCs) and non-endometriosis
      (NE-MenSCs) women differed regarding their morphology, CD marker expression
      pattern, proliferation, invasion and adhesion capacities and their ability to
      express certain immunomodulatory molecules. E-MenSCs were morphologically
      different from NE-MenSCs and showed higher expression of CD9, CD10 and CD29.
      Furthermore, E-MenSCs had higher proliferation and invasion potentials compared
      with NE-MenSCs. The amount of indoleamine 2,3-dioxygenase-1 (IDO1) and
      cyclooxygenase-2 (COX-2) in E-MenSCs co-cultured with allogenic peripheral blood
      mononuclear cells (PBMCs) was shown to be higher both at the gene and protein
      levels, and higher IDO1 activity was detected in the endometriosis group.
      However, NE-MenSCs revealed increased concentrations of forkhead transcription
      factor-3 (FOXP3) when compared with E-MenSCs. Nonetheless, interferon (IFN)
      gamma, Interleukin (IL)-10 and monocyte chemoattractant protein-1 (MCP-1) levels
      were higher in the supernatant of E-MenSCs-PBMC co-cultures. Here, we showed that
      there are inherent differences between E-MenSCs and NE-MenSCs. These findings
      propose the key role MenSCs could play in the pathogenesis of endometriosis and
      further support the retrograde and stem cell theories of endometriosis. Hence,
      considering its renewable and easily available nature, menstrual blood could be
      viewed as a reliable and inexpensive material for studies addressing the cellular
      and molecular aspects of endometriosis. 

PMID- 24939731
TI  - Synthesis of Pd3Co1@Pt/C core-shell catalysts for methanol-tolerant cathodes of
      direct methanol fuel cells.
AB  - A composite Pd-based electrocatalyst consisting of a surface layer of Pt (5 wt.%)
      supported on a core Pd3Co1 alloy (95 wt.%) and dispersed as nanoparticles on a
      carbon black support (50 wt.% metal content) was prepared by using a sulphite
      complex route. The structure, composition, morphology, and surface properties of
      the catalyst were investigated by XRD, XRF, TEM, XPS and low-energy ion
      scattering spectroscopy (LE-ISS). The catalyst showed an enrichment of Pt on the
      surface and a smaller content of Co in the outermost layers. These
      characteristics allow a decrease the Pt content in direct methanol fuel cell
      cathode electrodes (from 1 to 0.06 mg cm(-2)) without significant decay in
      performance, due also to a better tolerance to methanol permeated through the
      polymer electrolyte membrane.

PMID- 24939732
TI  - Immune consequences of kinase inhibitors in development, undergoing clinical
      trials and in current use in melanoma treatment.
AB  - Metastatic malignant melanoma is a frequently fatal cancer. In recent years
      substantial therapeutic progress has occurred with the development of targeted
      kinase inhibitors and immunotherapeutics. Targeted therapies often result in
      rapid clinical benefit however responses are seldom durable. Immune therapies can
      result in durable disease control but responses may not be immediate. Optimal
      cancer therapy requires both rapid and durable cancer control and this can likely
      best be achieved by combining targeted therapies with immunotherapeutics. To
      achieve this, a detailed understanding of the immune consequences of the various
      kinase inhibitors, in development, clinical trial and currently used to treat
      melanoma is required. 

PMID- 24939733
TI  - Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet
      induced insulin resistance by the enhanced association of mTOR and rictor.
AB  - Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese
      individuals with insulin resistance, suggesting a correlation between GPAT
      function, triacylglycerol accumulation, and insulin resistance. We asked whether
      microsomal GPAT4, an isoform regulated by insulin, might contribute to the
      development of hepatic insulin resistance. Compared with control mice fed a high
      fat diet, Gpat4(-/-) mice were more glucose tolerant and were protected from
      insulin resistance. Overexpression of GPAT4 in mouse hepatocytes impaired insulin
      suppressed gluconeogenesis and insulin-stimulated glycogen synthesis. Impaired
      glucose homeostasis was coupled to inhibited insulin-stimulated phosphorylation
      of Akt(Ser473) and Akt(Thr308). GPAT4 overexpression inhibited rictor's
      association with the mammalian target of rapamycin (mTOR), and mTOR complex 2
      (mTORC2) activity. Compared with overexpressed GPAT3 in mouse hepatocytes, GPAT4
      overexpression increased phosphatidic acid (PA), especially di16:0-PA.
      Conversely, in Gpat4(-/-) hepatocytes, both mTOR/rictor association and mTORC2
      activity increased, and the content of PA in Gpat4(-/-) hepatocytes was lower
      than in controls, with the greatest decrease in 16:0-PA species. Compared with
      controls, liver and skeletal muscle from Gpat4(-/-)-deficient mice fed a high-fat
      diet were more insulin sensitive and had a lower hepatic content of di16:0-PA.
      Taken together, these data demonstrate that a GPAT4-derived lipid signal, likely
      di16:0-PA, impairs insulin signaling in mouse liver and contributes to hepatic
      insulin resistance.

PMID- 24939734
TI  - Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride
      accumulation.
AB  - Increased leptin levels have been suggested to contribute to cardiac hypertrophy
      and attenuate cardiac lipid accumulation in obesity, although it has been
      difficult to separate leptin's direct effects from those caused by changes in
      body weight and adiposity. To determine whether leptin attenuates cardiac lipid
      accumulation in obesity or directly causes left ventricular hypertrophy (LVH), we
      generated a novel mouse model in which the long form of the leptin receptor
      (LepR) was "rescued" only in cardiomyocytes of obese db/db mice. Reexpression of
      cardiomyocyte leptin receptors in db/db mice did not cause LVH but reduced
      cardiac triglycerides and improved cardiac function. Compared with lean wild-type
      (WT) or db/db-cardiac LepR rescue mice, db/db mice exhibited significantly lower
      E/A ratio, a measurement of early to late diastolic filling, which averaged 1.5
      +/- 0.07 in db/db vs. 1.9 +/- 0.08 and 1.8 +/- 0.11 in WT and db/db-cardiac LepR
      rescue mice, respectively. No differences in systolic function were observed.
      Although db/db and db/db-cardiac LepR rescue mice exhibited similar increases in
      plasma triglycerides, insulin, glucose, and body weight, cardiac triglycerides
      were significantly higher in db/db compared with WT and db/db cardiac LepR rescue
      mice, averaging 13.4 +/- 4.2 vs. 3.8 +/- 1.6 vs. 3.8 +/- 0.7 mg/g, respectively.
      These results demonstrate that despite significant obesity and increases in
      plasma glucose and triglycerides, db/db cardiac LepR rescue mice are protected
      against myocardial lipid accumulation. However, we found no evidence that leptin
      directly causes LVH. 

PMID- 24939735
TI  - Heritability of fat accumulation in white adipocytes.
AB  - Since individual cells from freshly isolated white adipose tissue (WAT) exhibit
      variable levels of fat accumulation, we attempted to determine which factor(s)
      cause this variation. We used primary WAT cells from adult mice and the mouse 3T3
      L1 cell-line of preadipocytes for these studies. Cells were labeled with BODIPY
      (boron-dipyrromethene) lipid probe, a marker for fat accumulation in live cells,
      and sorted on a fluorescence-activated cell sorter into two populations
      exhibiting low or high BODIPY fluorescence intensity. After more than 12
      doublings as dedifferentiated cells in growth medium, the sorted populations were
      exposed to adipogenic medium for 7 days and analyzed for BODIPY accumulation and
      mRNA expression of adipogenic markers. WAT-derived cells initially sorted to have
      low or high BODIPY fluorescence intensity maintained a similar low or high lipid
      phenotype after redifferentiation. Cell surface TSH receptor expression, which is
      known to increase when preadipocytes are differentiated, correlated with BODIPY
      staining in all states. mRNA levels of Ppargamma, Srebp1c, aP2, and Pref1, key
      regulators of adipogenesis, and leptin, Glut4, Fasn, and Tshr, markers of
      adipocyte differentiation, correlated with the levels of fat accumulation.
      Overexpression of Ppargamma in 3T3-L1 cells, as expected, caused cells from low-
      and high-BODIPY populations to accumulate more fat. More importantly, prior to
      differentiation, the endogenous Ppargamma promoter exhibited higher levels of
      acetylated histone H3, an activatory modification, in high-BODIPY- compared with
      low-BODIPY-derived populations. We conclude that fat accumulation is a heritable
      trait in WAT and that epigenetic modification on the Ppargamma promoter
      contributes to this heritability. 

PMID- 24939736
TI  - The aging suppressor klotho: a potential regulator of growth hormone secretion.
AB  - Klotho is a transmembranal protein highly expressed in the kidneys, choroid
      plexus, and anterior pituitary. Klotho can also be cleaved and shed and acts as a
      circulating hormone. Klotho-deficient mice (kl/kl mice) develop a phenotype
      resembling early aging. Several lines of evidence suggest a role for klotho in
      the regulation of growth hormone (GH) secretion. The kl/kl mice are smaller
      compared with their wild-type counterparts, and their somatotropes show reduced
      numbers of secretory granules. Moreover, klotho is a potent inhibitor of the IGF
      I pathway, a negative regulator of GH secretion. Therefore, we hypothesized that
      klotho may enhance GH secretion. The effect of klotho on GH secretion was
      examined in GH3 rat somatotrophs, cultured rat pituitaries, and cultured human GH
      secreting adenomas. In all three models, klotho treatment increased GH secretion.
      Prolonged treatment of mice with intraperitoneal klotho injections increased mRNA
      levels of IGF-I and IGF-I-binding protein-3 mRNA in the liver, reflecting
      increased serum GH levels. In accord with its ability to inhibit the IGF-I
      pathway, klotho partially restored the inhibitory effect of IGF-I on GH
      secretion. Klotho is known to be a positive regulator of basic bFGF signaling. We
      studied rat pituitaries and human adenoma cultures and noted that bFGF increased
      GH secretion and stimulated ERK1/2 phosphorylation. Both effects were augmented
      following treatment with klotho. Taken together, our data indicate for the first
      time that klotho is a positive regulator of GH secretion and suggest the IGF-I
      and bFGF pathways as potential mediators of this effect. 

PMID- 24939737
TI  - Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic
      steatosis, and type 2 diabetes in mice without impacting the reproductive tract.
AB  - Despite the capacity of estrogens to favorably regulate body composition and
      glucose homeostasis, their use to combat obesity and type 2 diabetes is not
      feasible, because they promote sex steroid-responsive cancers. The novel
      selective estrogen receptor modulator (SERM) bazedoxifene acetate (BZA) uniquely
      antagonizes both breast cancer development and estrogen-related changes in the
      female reproductive tract. How BZA administered with conjugated estrogen (CE) or
      alone impacts metabolism is unknown. The effects of BZA or CE + BZA on body
      composition and glucose homeostasis were determined in ovariectomized female mice
      fed a Western diet for 10-12 wk. In contrast to vehicle, estradiol (E2), CE, BZA,
      and CE + BZA equally prevented body weight gain by 50%. In parallel, all
      treatments caused equal attenuation of the increase in body fat mass invoked by
      the diet as well as the increases in subcutaneous and visceral white adipose
      tissue. Diet-induced hepatic steatosis was attenuated by E2 or CE, and BZA alone
      or with CE provided even greater steatosis prevention; all interventions improved
      pyruvate tolerance tests. Glucose tolerance tests and HOMA-IR were improved by
      E2, CE, and CE + BZA. Whereas E2 or CE alone invoked a uterotrophic response, BZA
      alone or CE + BZA had negligible impact on the uterus. Thus, CE + BZA affords
      protection from diet-induced adiposity, hepatic steatosis, and insulin resistance
      with minimal impact on the female reproductive tract in mice. These combined
      agents may provide a valuable new means to favorably regulate body composition
      and glucose homeostasis and combat fatty liver.

PMID- 24939738
TI  - An unusual cause of simultaneous common bile and pancreatic duct dilation.
AB  - Simultaneous dilation of both the common bile duct and the pancreatic duct
      (double-duct sign) is usually because of ampullary or pancreatic tumours. Here we
      report an unusual cause of double-duct dilation; we describe the case of a 49
      year-old female who developed afferent loop syndrome after pylorus-preserving
      pancreaticoduodenectomy: cross-sectional imaging of the abdomen revealed a double
      duct sign. 

PMID- 24939739
TI  - Salt: a taste of death?

PMID- 24939741
TI  - Importance of healthcare utilization and multimorbidity level in choosing a
      primary care provider in Sweden.
AB  - OBJECTIVE: To study the associations between active choice of primary care
      provider and healthcare utilization, multimorbidity, age, and sex, comparing data
      from primary care and all healthcare in a Swedish population. DESIGN: Descriptive
      cross-sectional study using descriptive analyses including t-test, correlations,
      and logistic regression modelling in four separate models. SETTING AND SUBJECTS:
      The population (151 731) and all healthcare in Blekinge in 2007. MAIN OUTCOME
      MEASURE: Actively or passively listed in primary care, registered on 31 December
      2007. RESULTS: Number of consultations (OR 1.31, 95% CI 1.30-1.32),
      multimorbidity level (OR 1.69, 95% CI 1.67-1.70), age (OR 1.03, 95% CI 1.03
      1.03), and sex (OR for men 0.67, 95% CI 0.65-0.68) were all associated with
      registered active listing in primary care. Active listing was more strongly
      associated with number of consultations and multimorbidity level using primary
      care data (OR 2.11, 95% CI 2.08-2.15 and OR 2.14, 95% CI 2.11-2.17, respectively)
      than using data from all healthcare. Number of consultations and multimorbidity
      level were correlated and had similar associations with active listing in primary
      care. Modelling number of consultations, multimorbidity level, age, and sex gave
      four separate models with about 70% explanatory power for active listing in
      primary care. Combining number of consultations and multimorbidity did not
      improve the models. CONCLUSIONS: Number of consultations and multimorbidity level
      were associated with active listing in primary care. These factors were also
      associated with each other differently in primary care than in all healthcare.
      More complex models including non-health-related individual characteristics and
      healthcare-related factors are needed to increase explanatory power.

PMID- 24939740
TI  - GP and patient predictions of sick-listing duration: how well do they correspond?
      A prospective observational study.
AB  - OBJECTIVE: To explore how well physicians and patients predict sick-listing
      duration and the correspondence between their respective predictions. To study
      possible gender differences concerning prediction accuracy. DESIGN: Prospective
      observational study. SETTING: Two medium-sized primary care centres (PCC) in
      western Sweden. SUBJECTS: GPs at the PCCs and attending patients sick-listed for
      > 14 days. MAIN OUTCOME MEASURES: Sick-listing duration; patients' and GPs'
      predictions of the total duration of the individual patient's sick-listing.
      RESULTS: A total of 127 patients (93 women, 34 men, mean age 45 years) and 10 GPs
      participated in the study. Neither the GPs nor the patients were able to predict
      the interval until return to work with high accuracy. The GPs' and the patients'
      perceptions concurred in only 26% of cases. There was a significant difference in
      the correspondence between the GPs' and patients' respective predictions of sick
      listing duration compared with the actual duration. GPs' predictions were more
      accurate for medium-length duration (1.5-6 months), while patients' predictions
      were more accurate for long-duration (> 6 months) sick-listing. Patients with
      less education predicted long duration of sick-listing more accurately than those
      with more education. There was no significant difference between male and female
      patients' accuracy of prediction, or between GPs' accuracy of prediction of male
      vs. female patients' sick-listing duration. CONCLUSIONS: Prediction of total sick
      listing duration was hard for both GP and patient; their respective predictions
      corresponded in only one-quarter of the cases. No gender differences were
      observed in the accuracy of prediction.

PMID- 24939743
TI  - Market for e-cigarettes includes 466 brands and 7764 unique flavours.

PMID- 24939742
TI  - mRNA-Seq and microRNA-Seq whole-transcriptome analyses of rhesus monkey embryonic
      stem cell neural differentiation revealed the potential regulators of rosette
      neural stem cells.
AB  - Rosette neural stem cells (R-NSCs) represent early stage of neural development
      and possess full neural differentiation and regionalization capacities. R-NSCs
      are considered as stem cells of neural lineage and have important implications in
      the study of neurogenesis and cell replacement therapy. However, the molecules
      regulating their functional properties remain largely unknown. Rhesus monkey is
      an ideal model to study human neural degenerative diseases and plays intermediate
      translational roles as therapeutic strategies evolved from rodent systems to
      human clinical applications. In this study, we derived R-NSCs from rhesus monkey
      embryonic stem cells (ESCs) and systematically investigated the unique
      expressions of mRNAs, microRNAs (miRNAs), and signalling pathways by genome-wide
      comparison of the mRNA and miRNA profilings of ESCs, R-NSCs at early (R-NSCP1)
      and late (R-NSCP6) passages, and neural progenitor cells. Apart from the R-NSCP1
      specific protein-coding genes and miRNAs, we identified several pathways
      including Hedgehog and Wnt highly activated in R-NSCP1. The possible regulatory
      interactions among the miRNAs, protein-coding genes, and signalling pathways were
      proposed. Besides, many genes with alternative splicing switch were identified at
      R-NSCP1. These data provided valuable resource to understand the regulation of
      early neurogenesis and to better manipulate the R-NSCs for cell replacement
      therapy. 

PMID- 24939744
TI  - Cigarette smoking and pulmonary function in adult survivors of childhood cancer
      exposed to pulmonary-toxic therapy: results from the St. Jude lifetime cohort
      study.
AB  - Treatments for childhood cancer can impair pulmonary function. We assessed the
      potential impact of cigarette smoking on pulmonary function in 433 adult
      childhood cancer survivors (CCS) who received pulmonary-toxic therapy, using
      single breath diffusion capacity for carbon monoxide corrected for hemoglobin
      (DLCOcorr), forced expiratory volume in 1 second (FEV1), forced vital capacity
      (FVC), and total lung capacity (TLC). FEV1/FVC median values among current [1.00;
      interquartile range (IQR): 0.94-1.04] and former smokers (0.98; IQR: 0.93-1.04)
      were lower than those who had never smoked (1.02; IQR: 0.96-1.06; P = 0.003).
      Median FEV1/FVC values were lower among those who smoked >= 6 pack-years (0.99;
      IQR: 0.92-1.03) and those who smoked <6 pack-years (1.00; IQR: 0.94-1.04), than
      among those who had never smoked (P = 0.005). Our findings suggest that CCSs have
      an increased risk for future obstructive and restrictive lung disease. Follow-up
      is needed to determine whether smoking imparts more than additive risk. Smoking
      prevention and cessation need to be a priority in this population.

PMID- 24939745
TI  - Advances in lipid-based colloid systems as drug carrier for topic delivery.
AB  - INTRODUCTION: Based on the advantages of transcutaneous delivery and the
      application status of nanocarriers in transcutaneous delivery, this paper
      critically reviews the correlation of using different lipid-based colloid systems
      as permeation enhancement model. Particularly noteworthy, mechanisms of different
      action pathways of lipid-based colloid systems for topic delivery are
      illustrated, including free drug pathway, lipids enhancement, penetration with
      intact carrier and transappendageal pathway. AREAS COVERED: The authors focus on
      theories and detailed researches about liposome, lipid nanocapsules, solid lipid
      nanoparticles and microemulsion and nanostructured lipid carriers, revealing the
      advances and application states of these carriers as transcutaneous delivery
      system. FORWARD LOOK: Although lipid-based colloid systems show great
      superiority, some forward-looking ideas should be brought on agendas. In the
      future, more attention should be focused on skin stimulation. Mechanisms must be
      established to secure more information about the influence of excipient matrix.
      Some other issues including smart preparation forms and storage stability are
      also of current concerns and need more detailed research.

PMID- 24939746
TI  - Magnetization amplified by structural disorder within nanometre-scale interface
      region.
AB  - Direct magnetization measurements from narrow, complex-shaped antiphase
      boundaries (APBs; that is, planar defect produced in any ordered crystals) are
      vitally important for advances in materials science and engineering. However, in
      depth examination of APBs has been hampered by the lack of experimental tools.
      Here, based on electron microscopy observations, we report the unusual
      relationship between APBs and ferromagnetic spin order in Fe70Al30. Thermally
      induced APBs show a finite width (2-3 nm), within which significant atomic
      disordering occurs. Electron holography studies revealed an unexpectedly large
      magnetic flux density at the APBs, amplified by approximately 60% (at 293 K)
      compared with the matrix value. At elevated temperatures, the specimens showed a
      peculiar spin texture wherein the ferromagnetic phase was confined within the APB
      region. These observations demonstrate ferromagnetism stabilized by structural
      disorder within APBs, which is in direct contrast to the traditional
      understanding. The results accordingly provide rich conceptual insights for
      engineering APB-induced phenomena. 

PMID- 24939748
TI  - Accurate characterization of single track-etched, conical nanopores.
AB  - Single track-etched conical nanopores in polymer foils have attracted
      considerable attention in recent years due to their potential applications in
      biosensing, nanofluidics, information processing, and other fields. The
      performance of a nanopore critically depends on the size and shape of its
      narrowest, nanometer-sized region. In this paper, we reconstructed the profiles
      of both doubly-conical and conical pores, using an algorithm based on
      conductometric measurements performed in the course of etching, coupled with SEM
      data. We showed that pore constriction deviates from the conical shape, and the
      deviation depends on the energy loss of the particle that produced the track.
      Funnel-like profiles of tracks of four ions with different atomic numbers were
      derived from experimental data. The simulations, using a Poisson-Nernst-Planck
      model, demonstrated that the ion current rectification properties of the funnel
      shaped asymmetrical pores significantly differ from those of conical ones if the
      tip radius of the pore is smaller than 10 nm. Upon subjecting to further etching,
      the pores gradually approach the "ideal" conical geometry, and the ion transport
      properties of these two pore configurations become almost indistinguishable. 

PMID- 24939747
TI  - Refractive index measurement of the mouse crystalline lens using optical
      coherence tomography.
AB  - In recent years, there has been a growing interest for using mouse models in
      refractive development and myopia research. The crystalline lens is a critical
      optical component of the mouse eye that occupies greater than 50% of the ocular
      space, and significant increases in thickness with age. However, changes in
      refractive index of the mouse crystalline lens are less known. In this study, we
      examined the changes in thickness and refractive index of the mouse crystalline
      lens for two different strains, wild-type (WT) and a nyx mutant (nob) over the
      course of normal visual development or after form deprivation. Refractive index
      and lens thickness measurements were made on ex vivo lenses using spectral domain
      optical coherence tomography (SD-OCT). Comparison of refractive index
      measurements on 5 standard ball lenses using the SD-OCT and their known
      refractive indices (manufacturer provided) indicated good precision (intra-class
      correlation coefficient, 0.998 and Bland-Altman coefficient of repeatability,
      0.116) of the SD-OCT to calculate mouse lens refractive index ex vivo. During
      normal visual development, lens thickness increased significantly with age for
      three different cohorts of mice, aged 4 (average thickness from both eyes; WT:
      1.78 +/- 0.03, nob: 1.79 +/- 0.08 mm), 10 (WT: 2.02 +/- 0.05, nob: 2.01 +/- 0.04
      mm) and 16 weeks (WT: 2.12 +/- 0.06, nob: 2.09 +/- 0.06 mm, p < 0.001). Lens
      thickness was not significantly different between the two strains at any age (p =
      0.557). For mice with normal vision, refractive index for isolated crystalline
      lenses in nob mice was significantly greater than WT mice (mean for all ages; WT:
      1.42 +/- 0.01, nob: 1.44 +/- 0.001, p < 0.001). After 4 weeks of form deprivation
      to the right eye using a skull-mounted goggling apparatus, a thinning of the
      crystalline lens was observed in both right and left eyes of goggled animals
      compared to their naive controls (average from both the right and the left eye)
      for both strains (p = 0.052). In form deprived mice, lens refractive index was
      significantly different between the goggled animals and non-goggled naive
      controls in nob mice, but not in WT mice (p = 0.009). Both eyes of goggled nob
      mice had significantly greater lens refractive index (goggled, 1.49 +/- 0.01;
      opposite, 1.47 +/- 0.03) compared to their naive controls (1.45 +/- 0.02, p <
      0.05). The results presented here suggest that there are genetic differences in
      the crystalline lens refractive index of the mouse eye, and that the lens
      refractive index in mice significantly increase with form deprivation. Research
      applications requiring precise optical measurements of the mouse eye should take
      these lens refractive indices into account when interpreting SD-OCT data. 

PMID- 24939749
TI  - [2009 pandemic influenza A (H1N1) virus infection treated with oseltamivir and
      possible association with acute pancreatitis in a 12 years old patient].

PMID- 24939751
TI  - Methods for Multilevel Ordinal Data in Prevention Research.
AB  - This paper discusses statistical models for multilevel ordinal data that may be
      more appropriate for prevention outcomes than models that assume continuous
      measurement and normality. Prevention outcomes often have distributions that make
      them inappropriate for many popular statistical models that assume normality and
      are more appropriately considered ordinal outcomes. Despite this, the modeling of
      ordinal outcomes is often not well understood. This article discusses ways to
      analyze multilevel ordinal outcomes that are clustered or longitudinal, including
      the proportional odds regression model for ordinal outcomes, which assumes that
      the covariate effects are the same across the levels of the ordinal outcome. The
      article will cover how to test this assumption and what to do if it is violated.
      It will also discuss application of these models using computer software
      programs. 

PMID- 24939752
TI  - Probable Tolosa-Hunt syndrome with a normal MRI.
AB  - BACKGROUND: We are reporting a rare case of a 60-year-old woman with a past
      history of end-stage renal disease and non-Hodgkin lymphoma who presented to our
      hospital with confusion, unilateral headache, painful ophthalmoplegia and ptosis.
      The patient was diagnosed clinically with Tolosa-Hunt syndrome (THS). RESULTS:
      THS is a diagnosis of exclusion. Other diseases were ruled out. Magnetic
      resonance imaging (MRI) of the brain and orbit was negative twice within a week.
      The patient was treated with corticosteroids with marked improvement of the
      orbital pain and headache and mild improvement of the cranial nerves palsy.
      CONCLUSION: Clinical diagnosis of THS could be supported by radiological
      findings. According to the International Classification of Headache Disorders
      (ICHD)-3 beta diagnostic criteria, the diagnosis must be confirmed with an
      abnormal MRI and/or pathological sample. We add to the previous findings of THS
      with a normal MRI. Although MRI plays a crucial role in differential diagnosis,
      it should not, nor should the biopsy, be a must for the diagnosis. Limitations of
      using MRI in some patients are another problem.

PMID- 24939750
TI  - Poly(ADP-ribosyl)ation is involved in the epigenetic control of TET1 gene
      transcription.
AB  - TET enzymes are the epigenetic factors involved in the formation of the sixth DNA
      base 5-hydroxymethylcytosine, whose deregulation has been associated with
      tumorigenesis. In particular, TET1 acts as tumor suppressor preventing cell
      proliferation and tumor metastasis and it has frequently been found down
      regulated in cancer. Thus, considering the importance of a tight control of TET1
      expression, the epigenetic mechanisms involved in the transcriptional regulation
      of TET1 gene are here investigated. The involvement of poly(ADP-ribosyl)ation in
      the control of DNA and histone methylation on TET1 gene was examined. PARP
      activity is able to positively regulate TET1 expression maintaining a permissive
      chromatin state characterized by DNA hypomethylation of TET1 CpG island as well
      as high levels of H3K4 trimethylation. These epigenetic modifications were
      affected by PAR depletion causing TET1 down-regulation and in turn reduced
      recruitment of TET1 protein on HOXA9 target gene. In conclusion, this work shows
      that PARP activity is a transcriptional regulator of TET1 gene through the
      control of epigenetic events and it suggests that deregulation of these
      mechanisms could account for TET1 repression in cancer.

PMID- 24939753
TI  - Bias in a protocol for a meta-analysis of 5-HTTLPR, stress, and depression.

PMID- 24939754
TI  - Primary biliary cirrhosis: proposal for a new simple histological scoring system.
AB  - BACKGROUND & AIMS: A simple and reproducible evaluation of non diagnostic
      histological lesions related to prognosis remains crucial in primary biliary
      cirrhosis (PBC). Presently there is no satisfactory simple scoring system
      analysing them reliably. We elaborated a semi-quantitative scoring system that
      assesses fibrosis, lymphocytic interface hepatitis (LIH) and ductopenia,
      separately. This study was aimed to evaluate its intra/interobserver
      reproducibility and its correlation with the main biochemical data. METHODS:
      Liver biopsies from 33 consecutive newly diagnosed PBC patients were
      independently analysed by five liver pathologists. Fibrosis was classified into
      five stages (portal/periportal fibrosis/few septa/numerous septa/cirrhosis) and
      LIH into four grades. The bile duct ratio (BDR), i.e. ratio of the number of
      portal tracts with ducts to total number of portal tracts, Ludwig's and Scheuer's
      stages were evaluated. Intra and interobserver agreements were assessed.
      Histological results were correlated to the biochemical data. RESULTS: Most
      patients had an early disease on clinical and biological parameters. The biopsies
      measured 23 mm on average (range 12 - 40 mm). Intraobserver reproducibility was
      substantial for fibrosis (kappa = 0.68), LIH (kappa = 0.69) and BDR (ICC = 0.69).
      Interobserver agreement for fibrosis was fair with the 5-class system (kappa =
      0.36), moderate with a 4-class system (kappa = 0.56). moderate for LIH (kappa =
      0.59) and BDR (ICC = 0.50). Ludwig's and Scheuer's staging showed a fair
      interobserver agreement (kappa = 0.32, kappa = 0.31 respectively). Our system
      showed better correlations with biochemistry than Ludwig's and Scheuer's systems
      did. CONCLUSIONS: This simple scoring system, assessing fibrosis, LIH and BDR
      separately, has a substantial intraobserver and a moderate interobserver
      reproducibility. Its prognostic relevance has to be evaluated.

PMID- 24939756
TI  - Strategies for the modulation of phase II metabolism in a series of PKCepsilon
      inhibitors.
AB  - Extensive phase II metabolism of an advanced PKCepsilon inhibitor resulted in sub
      optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O
      glucuronide metabolite as a standard was followed by three distinct strategies to
      specifically temper phase II metabolic degradation of the parent molecule. In
      this study, it was determined that the introduction of proximal polarity to the
      primary alcohol generally curbed O-glucuronidation and improved PK and physical
      chemical properties while maintaining potency against the target. Utilization of
      a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final
      compounds is also discussed. 

PMID- 24939757
TI  - Xylarianaphthol-1, a novel dinaphthofuran derivative, activates p21 promoter in a
      p53-independent manner.
AB  - Xylarianaphthol-1, a novel dinaphthofuran derivative, was isolated from a marine
      sponge-derived fungus of order Xylariales on the guidance of a bioassay using the
      transfected human osteosarcoma MG63 cells (MG63(luc+)). The chemical structure of
      xylarianaphthol-1 was determined from the (1)H and (13)C NMR analysis and was
      further confirmed by the total synthesis. Xylarianaphthol-1 activated p21
      promoter stably transfected in MG63 cells dose-dependently. Expression of p21
      protein in the wild-type MG63 cells was also increased by xylarianaphthol-1
      treatment. 

PMID- 24939758
TI  - Discovery and structure-activity relationships of phenyl
      benzenesulfonylhydrazides as novel indoleamine 2,3-dioxygenase inhibitors.
AB  - A novel class of phenyl benzenesulfonylhydrazides has been identified as potent
      inhibitors of indoleamine 2,3-dioxygenase (IDO), and their structure-activity
      relationship was explored. Coupling reactions between various benzenesulfonyl
      chlorides and phenylhydrazides were utilized to synthesize the sulfonylhydrazides
      bearing various substituents. Compound 3i exhibited 61 nM of IC50 in enzymatic
      assay and 172 nM of EC50 in the HeLa cell. The computational study of 3i
      suggested that the major interactions between 3i and IDO protein are the
      coordination of sulfone and heme iron, the hydrogen bonding and hydrophobic
      interactions between 3i and IDO. This novel class of IDO inhibitor provides a new
      direction to discover effective anti-cancer agents.

PMID- 24939759
TI  - Glutamate changes in anterior cingulate cortex following CCK-4 infusion.

PMID- 24939760
TI  - 'Acute shift in glutamate-concentrations following experimentally induced panic
      with cholecystokinin-tetrapeptide-a 3T-MRS study in healthy subjects'-a reply to
      the letter to the editor.

PMID- 24939764
TI  - So many things we do not know.

PMID- 24939762
TI  - Bladder exstrophy: current management and postoperative imaging.
AB  - Bladder exstrophy is a rare malformation characterized by an infra-umbilical
      abdominal wall defect, incomplete closure of the bladder with mucosa continuous
      with the abdominal wall, epispadias, and alterations in the pelvic bones and
      muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy
      on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy
      is the most common of these entities and is more common in boys. The goal of this
      paper is to describe common methods of repair and to provide an imaging review of
      the postoperative appearances. 

PMID- 24939765
TI  - Organ donation and ethics.

PMID- 24939767
TI  - [Re: The polypill--an alternative concept in cardiovascular prophylaxis].

PMID- 24939771
TI  - [Re: Biased judgement about whiplash from the Supreme Court].

PMID- 24939772
TI  - [O. Sjaastad & J.P. Hesselberg reply].

PMID- 24939773
TI  - Screening for cervical cancer--future perspectives.

PMID- 24939774
TI  - Why are results of organised mammography screening so difficult to interpret?

PMID- 24939775
TI  - Mammography screening should be discontinued.

PMID- 24939776
TI  - Are surrogate endpoints useful in clinical studies?

PMID- 24939777
TI  - Are quantitative and qualitative research misleading concepts?

PMID- 24939778
TI  - [Wise suggestions about abortion referral].

PMID- 24939780
TI  - Doctors' attitudes to organ donation.
AB  - BACKGROUND: There is an increasing need for organs for transplantation purposes.
      Knowledge and attitudes among the medical team may affect the donation process.
      When respiration and cardiac activity are being sustained by artificial means,
      Norwegian law requires angiographic evidence of cessation of cerebral circulation
      as well as clinical examination before an organ donation can be carried out. We
      wished to survey Norwegian doctors' attitudes to organ donation and how donation
      processes are being addressed. MATERIAL AND METHOD: A questionnaire with pre
      defined response alternatives was distributed to doctors in intensive-care units
      as well as to specialists and junior registrars in neurosurgery in Norwegian
      donor hospitals in 2008-2009. RESULTS: Altogether 435 doctors (55%) returned a
      completed questionnaire. A total of 315 of 420 (75%) responded that they would
      consider initiating organ-preserving treatment when there is no more hope for the
      patient, while 18% were uncertain and 7% responded that they would not consider
      this option. Altogether 68 of 424 (16%) maintained that if an organ donation was
      relevant and current legislation could be disregarded, clinical diagnostics would
      be sufficient to establish a diagnosis of death. Another 22% were uncertain,
      while 62% were of the opinion that clinical diagnostics would be insufficient. A
      total of 258 of 416 (62%) reported that in their opinion, the next of kin most
      often could understand the implications of total destruction of the brain when
      this was explained to them. INTERPRETATION: Future teaching should emphasise the
      opportunity for organ-preserving treatment in cases where a fatal outcome is
      expected.

PMID- 24939782
TI  - Spasms in legs--lesion in neck.

PMID- 24939781
TI  - Patients who terminate OMT--how do they fare?
AB  - BACKGROUND: OMT tends to involve treatment over an extended period of time. Some
      OMT patients terminate the treatment. There is a need for more knowledge about
      how these persons do following treatment. MATERIAL AND METHOD: We undertook a
      retrospective review of patient records at Sorlandet Hospital in Kristiansand for
      patients who had undergone OMT in the period 1998-2009. Data from 103 discharged
      patients were included in the study, registered on two occasions--31 December
      2009 and 30 June 2011. RESULTS: Of the 469 patients who started their OMT during
      the period of study, altogether 103 patients (22%) terminated the treatment. One
      half of the 103 patients who terminated their treatment did so because they no
      longer wanted OMT or failed to report to the hospital. The others terminated the
      treatment because they wanted medication from their GP other than OMT (n = 11),
      because they considered themselves to be no longer addicted and in need of
      treatment (n = 19) or because they maintained a considerable substance use (n =
      21). Seven patients wanted a planned tapering-off of OMT drugs. The status for
      these 103 discharged patients as of 31 December 2009 (median 1,034 days after
      discharge) was: uncontrolled substance use: 30%; dead: 17%; other medication from
      GP: 14%; psychiatric treatment: 12%; imprisoned: 8%; OMT in another county: 2%;
      drug-free without maintenance treatment: 11%; unknown: 6%. Eighteen months later,
      altogether 36 of them had changed their status. The group with uncontrolled
      substance use (n = 31) had undergone the greatest change--altogether 14 were back
      in OMT, ten continued their substance use and four had died. INTERPRETATION: The
      OMT patients who terminated the treatment had a high rate of mortality.
      Approximately 10 % of those discharged lived stable drug-free lives without OMT
      medication during the period of observation.

PMID- 24939783
TI  - Man with macrocephaly, learning disability and multiple basal cell carcinomas.
AB  - Gorlin syndrome is a rare genetic condition in which patients may develop
      medulloblastomas, jaw cysts and basal cell carcinomas and show congenital
      skeletal malformations. If left undiagnosed, Gorlin syndrome can have a number of
      negative consequences. Early diagnosis and good follow-up is important for all
      patients with rare disorders. We wish to make doctors and dentists aware of
      Gorlin syndrome so that, whenever the syndrome is suspected or a patient has been
      diagnosed, the patient is referred for assessment, treatment and follow-up by
      specialists who know the disorder well. Dermatology departments at university
      hospitals and departments of medical genetics have a key role to play in
      assessment and follow-up. A national support group for Gorlin syndrome has been
      established, consisting of a dermatologist, oncologist, geneticist,
      paediatrician, specialist dentist, ophthalmologist, orthopaedic surgeon, plastic
      surgeon, oral and maxillofacial surgeon and counsellors. Patients, relatives and
      health professionals can contact the Centre for Rare Disorders directly for
      information about Gorlin syndrome, or to be put in touch with members of the
      group.

PMID- 24939784
TI  - [Opioid maintenance treatment--important treatment with dilemmas].

PMID- 24939799
TI  - Intertidal epilithic bacteria diversity changes along a naturally occurring
      carbon dioxide and pH gradient.
AB  - Intertidal epilithic bacteria communities are important components of coastal
      ecosystems, yet few studies have assessed their diversity and how it may be
      affected by changing environmental parameters. Submarine CO2 seeps produce
      localised areas of CO2-enriched seawater with reduced pH levels. We utilised the
      seawater pH/CO2 gradient at Levante Bay (Italy) to test the hypothesis that
      epilithic bacteria communities are modified by exposure to seawater with the
      varying chemical parameters. Biofilms were sampled from three sites exposed to
      seawater with different pH/CO2 levels and diversity determined using high
      throughput sequencing of 16S rRNA genes. Seawater pCO2 concentrations were
      increased from ambient at site 1 to 621 MUatm at site 2 and 1654 MUatm site 3,
      similar to the predicated future oceans beyond 2050 and 2150, respectively. Alpha
      diversity of total bacteria communities and Cyanobacteria communities was
      significantly different between sites (anova P < 0.05). Comparison between sites
      showed that bacteria communities and Cyanobacteria communities were significantly
      different (anosim P < 0.01; permanova P < 0.01). Proteobacteria, Bacteroidetes
      and Cyanobacteria dominated all communities; however, there were differences
      between sites in the relative abundance of specific orders. This study provides
      the most detailed assessment of intertidal epilithic bacteria diversity and shows
      that diversity is significantly different along a seawater pH/CO2 gradient. This
      information supports the evaluation of the impacts of future ocean acidification
      on coastal marine ecosystems.

PMID- 24939800
TI  - Phytotoxic steroidal saponins from Agave offoyana leaves.
AB  - A bioassay-guided fractionation of Agave offoyana leaves led to the isolation of
      five steroidal saponins (1-5) along with six known saponins (6-11). The compounds
      were identified as (25R)-spirost-5-en-2alpha,3beta-diol-12-one 3-O-{alpha-l
      rhamnopyranosyl-(1->3)-O-beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1
      >3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (1), (25R)
      spirost-5-en-3beta-ol-12-one 3-O-{alpha-l-rhamnopyranosyl-(1->3)-O-beta-d
      glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1->3)]-O-beta-d-glucopyranosyl-(1
      >4)-O-beta-d-galactopyranoside} (2), (25R)-spirost-5-en-3beta-ol-12-one 3-O-{beta
      d-xylopyranosyl-(1->3)-O-beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1
      >3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (3), (25R)-26-O
      beta-d-glucopyranosylfurost-5-en-3beta,22alpha,26-triol-12-one 3-O-{alpha-l
      rhamnopyranosyl-(1->3)-O-beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1
      >3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (4) and (25R)-26
      O-beta-d-glucopyranosylfurost-5-en-3beta,22alpha,26-triol-12-one 3-O-{beta-d
      xylopyranosyl-(1->3)-O-beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1
      >3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (5) by
      comprehensive spectroscopic analysis, including one- and two-dimensional NMR
      techniques, mass spectrometry and chemical methods. The phytotoxicity of the
      isolated compounds on the standard target species Lactuca sativa was evaluated. 

PMID- 24939801
TI  - Effect of intestinal colonisation by two Lactobacillus strains on the immune
      response of gnotobiotic mice.
AB  - The effect of intestinal colonisation on the immune system was investigated in
      germ-free mice monoassociated with Lactobacillus strains isolated from calf
      faeces. Single doses of Lactobacillus acidophilus L36 or Lactobacillus salivarius
      L38 were administered to germ-free mice by intragastric gavage. Ten days later,
      the mice were euthanised. Gene expression levels of interleukin 5 (IL-5), IL-6,
      IL-10, IL-12b, IL-17a, gamma interferon (IFN-gamma), transforming growth factor
      beta 1 (TGF-beta1), and tumour necrosis factor alpha (TNF-alpha) were quantified
      in segments of the small and large intestines by real time quantitative
      polymerase chain reaction. All the mice were colonised rapidly after
      Lactobacillus administration with intestinal counts ranging from 6.53 to 8.26 log
      cfu/g. L. acidophilus L36 administration increased the expression of cytokines
      involved with the Th2 (IL-5, IL-6 and TGF-beta1) and Th17 (IL-17a, TNF-alpha and
      IL-6) inflammatory response, whereas L. salivarius L38 appeared to stimulate a
      pattern of less diversified cytokines in the intestine. Intragastric gavage of L.
      acidophilus L36 and L. salivarius L38 induced similar levels of colonisation in
      the digestive tracts of germ-free mice but stimulated different immune responses
      in the intestinal mucosa. The different immunomodulation patterns might
      facilitate the potential use of these lactobacilli as probiotics to treat
      distinct pathological conditions, for example protection against Citrobacter
      rodentium infection by stimulating IL-17 production. 

PMID- 24939802
TI  - How to select a guidewire: technical features and key characteristics.

PMID- 24939803
TI  - Acceptability and clinical outcomes of first- and second-trimester surgical
      abortion by suction aspiration in Colombia.
AB  - OBJECTIVE(S): Since partial decriminalization of abortion in Colombia, Orientame
      has provided legal abortion services through 15 weeks gestation in an outpatient
      primary care setting. We sought to document the safety and acceptability of the
      second trimester compared to the first-trimester surgical abortion in this
      setting. STUDY DESIGN: This was a prospective cohort study using a consecutive
      sample of 100 women undergoing surgical first-trimester abortion (11 weeks 6 days
      gestational age or less) and 200 women undergoing second-trimester abortion (12
      weeks 0 days-15 weeks 0 days) over a 5-month period in 2012. After obtaining
      informed consent, a trained interviewer collected demographic and clinical
      information from direct observation and the patient's clinical chart. The
      interviewer asked questions after the procedure regarding satisfaction with the
      procedure, physical pain and emotional discomfort. Fifteen days later, the
      interviewer assessed satisfaction with the procedure and any delayed
      complications. RESULTS: There were no major complications and seven minor
      complications. Average measured blood loss was 37.87 mL in the first trimester
      and 109 mL in the second trimester (p<.001). Following the procedure, more second
      trimester patients reported being very satisfied (81% vs. 94%, p=.006).
      Satisfaction was similar between groups at follow-up. There were no differences
      in reported emotional discomfort after the procedure or at follow-up, with the
      majority reporting no emotional discomfort. The majority of women (99%) stated
      that they would recommend the clinic to a friend or family member. CONCLUSIONS:
      Second-trimester surgical abortion in an outpatient primary care setting in
      Colombia can be provided safely, and satisfaction with these services is high.
      IMPLICATIONS: This is one of the first studies from Latin America, a region with
      a high proportion of maternal mortality due to unsafe abortion, which documents
      the safety and acceptability of surgical abortion in an outpatient primary care
      setting. Findings could support increased access to safe abortion services,
      particularly in the second trimester.

PMID- 24939804
TI  - Long-range electronic reconstruction to a dxz,yz-dominated Fermi surface below
      the LaAlO3/SrTiO3 interface.
AB  - Low dimensionality, broken symmetry and easily-modulated carrier concentrations
      provoke novel electronic phase emergence at oxide interfaces. However, the
      spatial extent of such reconstructions - i.e. the interfacial "depth" - remains
      unclear. Examining LaAlO3/SrTiO3 heterostructures at previously unexplored
      carrier densities n(2D) >= 6.9 * 10(14) cm(-2), we observe a Shubnikov-de Haas
      effect for small in-plane fields, characteristic of an anisotropic 3D Fermi
      surface with preferential dxz,yz orbital occupancy extending over at least 100 nm
      perpendicular to the interface. Quantum oscillations from the 3D Fermi surface of
      bulk doped SrTiO3 emerge simultaneously at higher n(2D). We distinguish three
      areas in doped perovskite heterostructures: narrow (<20 nm) 2D interfaces housing
      superconductivity and/or other emergent phases, electronically isotropic regions
      far (>120 nm) from the interface and new intermediate zones where interfacial
      proximity renormalises the electronic structure relative to the bulk.

PMID- 24939805
TI  - Inhibitory effects of hydroxysafflor yellow A on PDGF-BB-induced proliferation
      and migration of vascular smooth muscle cells via mediating Akt signaling.
AB  - The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs)
      are key pathological factors in the initiation and progression of vascular
      disorders, including arteriosclerosis and restenosis following percutaneous
      coronary intervention (PCI). Hydroxysafflor yellow A (HSYA), the main component
      of the safflower yellow pigments, has widely been used for the treatment of
      cardiovascular diseases in traditional Chinese medicine. However, to the best of
      our knowledge, there are no studies investigating the pharmaceutical effect of
      HSYA on VSMCs or the underlying molecular mechanism. The present study aimed to
      investigate the effect of HSYA on platelet-derived growth factor (PDGF)-BB
      stimulated VSMC proliferation and migration. HSYA significantly inhibited PDGF-BB
      stimulated VSMC proliferation and, in response to PDGF-BB-stimulation, VSMCs
      dedifferentiated into a proliferative phenotype. However, HSYA effectively
      reversed this phenotype switching. In addition, the production of nitrous oxide
      and cyclic guanosine monophosphate induced by PDGF-BB was also suppressed by
      HSYA, and HSYA markedly inhibited PDGF-BB-stimulated VSMC migration.
      Investigation of the molecular mechanism revealed that HSYA inhibited PDGF-BB
      induced activation of Akt signaling. In addition, HSYA also suppressed PDGF-BB
      stimulated upregulation of cell cycle related proteins and heme oxygenase-1. In
      conclusion, HSYA was able to inhibit PDGF-BB-stimulated VSMC proliferation and
      migration, partially via suppressing PDGF-BB-induced Akt signaling activation.
      Therefore, HSYA may be useful for the prevention and treatment of cardiovascular
      diseases, including atherosclerosis and restenosis following PCI.

PMID- 24939806
TI  - Depression and the older medical patient--when and how to intervene.
AB  - Depression in the elderly, particularly those with chronic physical health
      problems, is a common, but complex problem. In this paper we review the research
      literature on both the epidemiology and management of depression in the older
      medical patient. After a general overview of depression in the elderly, we
      discuss some of the particular issues relevant to depression and co-morbid
      physical illness amongst elderly patients. Depression can be difficult to
      diagnose in medically unwell older adults, particularly when there is substantial
      overlap in symptomatology. The epidemiology and evidence base for the treatment
      of depression in a number of chronic health problems common in an older adults
      population are then discussed, specifically cardiac disease, cerebrovascular
      disease, cancer, chronic kidney disease, chronic obstructive pulmonary disease,
      and Parkinson's disease. For many of these conditions there is emerging evidence
      that treatments can be effective in reducing depressive symptoms. However, these
      potential benefits need to be balanced against the often-increased risk of
      adverse events or interactions with medical treatments. Although co-morbid
      depression is consistently associated with poorer medical outcomes, there is
      limited evidence that standard anti-depressive therapy has additional benefits in
      terms of physical health outcomes. Collaborative care models appear particularly
      well suited to medically unwell older adult patients, and may provide more
      generalised benefits across both mental and physical health measures. 

PMID- 24939807
TI  - The prevalence of type 2 diabetes mellitus among older people in Africa: a
      systematic review study protocol.
AB  - INTRODUCTION: The number of people with diabetes in Africa is projected to
      increase substantially in the next two decades, due to factors including rapid
      urbanisation, adoption of unhealthy diets and exercise patterns and the ageing of
      the population. There are currently uncertainties regarding the incidence,
      prevalence and management patterns of diabetes in older people across the
      diversity of African countries. We wish to perform a systematic review to
      determine the prevalence of type 2 diabetes in Africa in the older individual,
      over the age of 55 years, reported in studies from 2000 to 2013. METHODS AND
      ANALYSES: A comprehensive literature search among a number of databases will be
      undertaken, using an African search filter to identify diabetes prevalence
      studies that were published from 2000 to 2013. Full copies of articles identified
      by the search, and considered to meet the inclusion criteria, will be obtained
      for data extraction and synthesis. Statistical analysis of the primary measures,
      fasting plasma glucose (FPG) and oral glucose tolerance test will include two
      steps: (1) identification of data sources and documenting estimates and (2)
      application of the random-effects meta-analysis model to aggregate prevalence
      estimates and account for between study variability in calculating the overall
      pooled estimates and 95% CI for diabetes prevalence. Heterogeneity will be
      evaluated using the I(2) statistic to determine the extent of variation in effect
      estimates that is due to heterogeneity rather than chance. This systematic review
      will be reported according to the Preferred Reporting Items for Systematic
      reviews and Meta-Analyses (PRISMA). ETHICS AND DISSEMINATION: Ethics is not
      required for this study, given that this is a protocol for a systematic review,
      which utilises published data. The findings of this study will be widely
      disseminated through peer-reviewed publications and conference presentations.

PMID- 24939808
TI  - Exploring perceived barriers, drivers, impacts and the need for evaluation of
      public involvement in health and social care research: a modified Delphi study.
AB  - OBJECTIVE: To explore areas of consensus and conflict in relation to perceived
      public involvement (PI) barriers and drivers, perceived impacts of PI and ways of
      evaluating PI approaches in health and social care research. BACKGROUND:
      Internationally and within the UK the recognition of potential benefits of PI in
      health and social care research is gathering momentum and PI is increasingly
      identified by organisations as a prerequisite for funding. However, there is
      relatively little examination of the impacts of PI and how those impacts might be
      measured. DESIGN: Mixed method, three-phase, modified Delphi technique, conducted
      as part of a larger MRC multiphase project. SAMPLE: Clinical and non-clinical
      academics, members of the public, research managers, commissioners and funders.
      FINDINGS: This study found high levels of consensus about the most important
      barriers and drivers to PI. There was acknowledgement that tokenism was common in
      relation to PI; and strong support for the view that demonstrating the impacts
      and value of PI was made more difficult by tokenistic practice. PI was seen as
      having intrinsic value; nonetheless, there was clear support for the importance
      of evaluating its impact. Research team cohesion and appropriate resources were
      considered essential to effective PI implementation. Panellists agreed that PI
      can be challenging, but can be facilitated by clear guidance, together with
      models of good practice and measurable standards. CONCLUSIONS: This study is the
      first to present empirical evidence of the opinions voiced by key stakeholders on
      areas of consensus and conflict in relation to perceived PI barriers and drivers,
      perceived impacts of PI and the need to evaluate PI. As such it further
      contributes to debate around best practice in PI, the potential for tokenism and
      how best to evaluate the impacts of PI. These findings have been used in the
      development of the Public Involvement Impact Assessment Framework (PiiAF), an
      online resource which offers guidance to researchers and members of the public
      involved in the PI process.

PMID- 24939809
TI  - Current practice of venous thromboembolism prevention in acute trusts: a
      qualitative study.
AB  - OBJECTIVE: To explore the current practice of venous thromboembolism (VTE)
      prevention in acute trusts. DESIGN: A qualitative research design was used to
      explore the perceived current practice of thromboprophylaxis, and knowledge and
      experience of VTE prevention. Data were collected via interviews with personnel
      from acute trusts and other relevant organisations and charities. Constant
      comparison was used to generate themes grounded in the data. SETTING: The UK.
      PARTICIPANTS: 17 participants, sampled due to their expertise and knowledge in
      the field of VTE, were interviewed for the study. RESULTS: No one felt directly
      responsible for VTE risk assessment and treatment in acute trusts. There were
      concerns whether any action takes place based on the risk assessment. Low levels
      of VTE knowledge existed throughout the system. CONCLUSIONS: Our study highlights
      the importance of continuous training to prevent VTE risk assessment being
      considered a tick box exercise and for clinicians to understand the significance
      of the procedure to ensure that VTE preventative measures are administered. It is
      essential that acute trust staff acknowledge that VTE prevention is the
      responsibility of everyone involved in a patient's care. Concerns remain around
      prophylaxis treatment, administration and contraindications.

PMID- 24939810
TI  - Termination of pregnancy for maternal indications at the limits of fetal
      viability: a retrospective cohort study in the Dutch tertiary care centres.
AB  - OBJECTIVE: Maternal morbidity, either pregnancy related or pre-existent, can
      become life threatening and of such severity as to warrant termination of
      pregnancy (TOP). In this situation, chances of fetal survival are usually poor,
      either because of low gestational age and/or because of the fetal effects of the
      maternal condition. Examples include severe growth restriction in pre-eclampsia
      and intrauterine infection due to the very early preterm prelabour rupture of
      membranes. There are very few reports on the prevalence of TOP for maternal
      indication at the limits of fetal viability. We investigated the prevalence of
      and indications for TOP on maternal indication in the 10 tertiary care centres in
      the Netherlands during the past decade. STUDY DESIGN: We conducted a
      retrospective review of the medical records of all women who underwent TOP for
      maternal indications between 22 and 27 completed weeks of gestation in all 10
      tertiary care centres from 2000 to 2009. RESULTS: During the study period, there
      were 1 929 470 deliveries; 163 052 (8.4%) of these took place in one of the 10
      tertiary care centres and 177 pregnancies were terminated for severe maternal
      disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for
      other reasons. The mean gestational age at TOP was 171 days (24(3/7))+/-10 days.
      No maternal deaths were recorded. The overall perinatal mortality was 99.4%.
      CONCLUSIONS: Over a 10-year period, TOP for maternal indications was performed in
      1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive
      disorders comprised three-quarters of the cases.

PMID- 24939811
TI  - Reliability of demographic and socioeconomic variables in predicting early
      initiation of breastfeeding: a replication analysis using the Kenya Demographic
      and Health Survey data.
AB  - OBJECTIVES: Examine the reliability of sociodemographic variables in predicting
      initiation of breastfeeding within an hour of birth (EarlyBF), using data from
      1998, 2003 and 2008-2009. STUDY DESIGN: A replication analysis using the Kenya
      Demographic and Health Survey (KDHS) data collected in 1998, 2003 and 2008-2009.
      The candidate predictor variables were child's gender, home or health facility
      place of birth, vaginal or caesarean mode of birth, urban or rural setting,
      province of residence, Wealth Index and maternal education, occupation, literacy
      and media exposure. SETTING: Kenya. PARTICIPANTS: 6375 dyads of mothers aged 15
      49 and their children aged 0-23 months (2125 dyads in each of the survey years).
      RESULTS: Mode of birth and province were statistically significant predictors of
      EarlyBF in 1998, 2003 and 2008-2009. Children delivered through caesarean section
      were non-EarlyBF in 1998 (OR 2.63, 95% CI 1.72 to 4.04), 2003 (OR 3.36, 95% CI
      1.83 to 6.16) and 2008 (OR 3.51, 95% CI 2.17 to 5.69). The same was true of those
      living in the Western province in 1998 (OR 2.67, 95% CI 1.61 to 4.43), 2003 (OR
      4.92, 95% CI 3.01 to 8.04) and 2008 (OR 6.07, 95% CI 3.54 to 10.39). CONCLUSIONS:
      The 1998 KDHS data do not provide the basis for reliable prediction of EarlyBF,
      with reliability conceptualised as replicability of findings using highly similar
      data sets from 2003 and 2008-2009. Most of the demographic and socioeconomic
      variables were unreliable predictors of EarlyBF. We speculate that activities in
      parts or all of Kenya changed the analysis context in the period between 1998 and
      2008-2009, and these changes were of a sufficient magnitude to affect the
      relationships under investigation. The degree to which this is a general problem
      in child health research is not known, calling for further research to
      investigate this methodological issue with other health end points and other
      data.

PMID- 24939812
TI  - The effect on physical performance of a functional assessment and immediate
      rehabilitation of acutely admitted elderly patients with reduced functional
      performance: the design of a randomised clinical trial.
AB  - INTRODUCTION: Illness and hospitalisation, even of short duration, pose separate
      risks for permanently reduced functional performance in elderly medical patients.
      Functional assessment in the acute pathway will ensure early detection of
      declining performance and form the basis for mobilisation during hospitalisation
      and subsequent rehabilitation. For optimal results rehabilitation should begin
      immediately after discharge.The aim of this study is to investigate the effect of
      a systematic functional assessment in the emergency department (ED) of elderly
      medical patients with reduced functional performance when combined with immediate
      postdischarge rehabilitation. METHOD AND ANALYSIS: The study is a two-way
      factorial randomised clinical trial. Participants will be recruited among
      patients admitted to the ED who are above 65 years of age with reduced functional
      performance. Patients will be randomly assigned to one of four groups: (1)
      functional assessment and immediate rehabilitation; (2) functional assessment and
      rehabilitation as usual; (3) assessment as usual and immediate rehabilitation;
      (4) assessment and rehabilitation as usual. PRIMARY OUTCOME: 30 s chair-stand
      test administered at admission and 3 weeks after discharge. ETHICS AND
      DISSEMINATION: The study has been approved by the Regional Scientific Ethical
      Committees of Southern Denmark in February 2014. The study findings will be
      published in peer-reviewed journals and presented at national and international
      conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier:
      NCT02062541.

PMID- 24939813
TI  - A mixed methods feasibility study to evaluate the use of a low-intensity, nurse
      delivered cognitive behavioural therapy for the treatment of irritable bowel
      syndrome.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is characterised by symptoms such as
      abdominal pain, constipation, diarrhoea and bloating. These symptoms impact on
      health-related quality of life, result in excess service utilisation and are a
      significant burden to healthcare systems. Certain mechanisms which underpin IBS
      can be explained by a biopsychosocial model which is amenable to psychological
      treatment using techniques such as cognitive behavioural therapy (CBT). While
      current evidence supports CBT interventions for this group of patients, access to
      these treatments within the UK healthcare system remains problematic. METHODS AND
      ANALYSIS: A mixed methods feasibility randomised controlled trial will be used to
      assess the feasibility of a low-intensity, nurse-delivered guided self-help
      intervention within secondary care gastrointestinal clinics. A total of 60
      participants will be allocated across four treatment conditions consisting of:
      high-intensity CBT delivered by a fully qualified cognitive behavioural
      therapist, low-intensity guided self-help delivered by a registered nurse, self
      help only without therapist support and a treatment as usual control condition.
      Participants from each of the intervention arms of the study will be interviewed
      in order to identify potential barriers and facilitators to the implementation of
      CBT interventions within clinical practice settings. Quantitative data will be
      analysed using descriptive statistics only. Qualitative data will be analysed
      using a group thematic analysis. ETHICS AND DISSEMINATION: This study will
      provide essential information regarding the feasibility of nurse-delivered CBT
      interventions within secondary care gastrointestinal clinics. The data gathered
      during this study would also provide useful information when planning a
      substantive trial and will assist funding bodies when considering investment in
      substantive trial funding. A favourable opinion for this research was granted by
      the Nottingham 2 Research Ethics Committee. TRIAL REGISTRATION NUMBER ISRCTN:
      83683687 (http://www.controlled-trials.com/ISRCTN83683687).

PMID- 24939814
TI  - Estimating treatment effects in randomised controlled trials with non-compliance:
      a simulation study.
AB  - OBJECTIVE: Randomised controlled trials (RCTs) are often considered as the gold
      standard for assessing new health interventions. Patients are randomly assigned
      to receive an intervention or control. The effect of the intervention can be
      estimated by comparing outcomes between groups, whose prognostic factors are
      expected to balance by randomisation. However, patients' non-compliance with
      their assigned treatment will undermine randomisation and potentially bias the
      estimate of treatment effect. Through simulation, we aim to compare common
      approaches in analysing non-compliant data under different non-compliant
      scenarios. SETTINGS: Based on a real study, we simulated hypothetical trials by
      varying three non-compliant factors: the type, randomness and degree of non
      compliance. We compared the intention-to-treat (ITT), as-treated (AT), per
      protocol (PP), instrumental variable (IV) and complier average casual effect
      (CACE) analyses to estimate large (50% improvement over the control), moderate
      (25% improvement) and null (same as the control) treatment effects. Different
      approaches were compared by the bias of estimate, mean square error (MSE) and 95%
      coverage of the true value. RESULTS: For a large or moderate treatment effect,
      the ITT estimate was considerably biased in all scenarios. The AT, PP, IV and
      CACE estimates were unbiased when non-compliant behaviours were random. The IV
      estimate was unbiased when non-compliant behaviours were symmetrically dependent
      on patients' conditions. The PP estimate was mostly unbiased when patients in the
      control group did not have access to the intervention. When the intervention was
      not different from the control, the ITT was less biased than the other
      approaches. Similar results were found when comparing the MSE and 95% coverage.
      CONCLUSIONS: The standard ITT analysis under non-compliance is biased when the
      intervention has a moderate or large effect. Alternative analyses can provide
      unbiased or less biased estimates. Based on the results, we make some suggestions
      on choosing optimal approaches for analysing specific non-compliant scenarios.

PMID- 24939815
TI  - A protocol for an exploratory phase I mixed-methods study of enhanced integrated
      care for care home residents with advanced dementia: the Compassion Intervention.
AB  - INTRODUCTION: In the UK approximately 700,000 people are living with, and a third
      of people aged over 65 will die with, dementia. People with dementia may receive
      poor quality care towards the end of life. We applied a realist approach and used
      mixed methods to develop a complex intervention to improve care for people with
      advanced dementia and their family carers. Consensus on intervention content was
      achieved using the RAND UCLA appropriateness method and mapped to sociological
      theories of process and impact. Core components are: (1) facilitation of
      integrated care, (2) education, training and support, (3) investment from
      commissioners and care providers. We present the protocol for an exploratory
      phase I study to implement components 1 and 2 in order to understand how the
      intervention operates in practice and to assess feasibility and acceptability.
      METHODS AND ANALYSIS: An 'Interdisciplinary Care Leader (ICL)' will work within
      two care homes, alongside staff and associated professionals to facilitate
      service integration, encourage structured needs assessment, develop the use of
      personal and advance care plans and support staff training. We will use
      qualitative and quantitative methods to collect data for a range of outcome and
      process measures to detect effects on individual residents, family carers, care
      home staff, the intervention team, the interdisciplinary team and wider systems.
      Analysis will include descriptive statistics summarising process and care home
      level data, individual demographic and clinical characteristics and data on
      symptom burden, clinical events and quality of care. Qualitative data will be
      explored using thematic analysis. Findings will inform a future phase II trial.
      ETHICS AND DISSEMINATION: Ethical approval was granted (REC reference
      14/LO/0370). We shall publish findings at conferences, in peer-reviewed journals,
      on the Marie Curie Cancer Care website and prepare reports for dissemination by
      organisations involved with end-of-life care and dementia.

PMID- 24939816
TI  - Characterization of microRNA expression in serous ovarian carcinoma.
AB  - Serous ovarian cancer is a major gynecologic malignancy with a poor 5-year
      survival rate. However, little is known regarding the behavior and genetics of
      ovarian tumorigenesis. MicroRNAs (miRNAs) have been shown to be dysregulated in
      ovarian carcinomas. To assess the miRNA expression profiles in serous ovarian
      cancer, we defined the patterns of miRNA expression in 100 formalin-fixed,
      paraffin-embedded ovarian cancer tissues blocks as well as 50 corresponding
      normal oviduct tissues using miRNA microarray. MiRNA expression profiling showed
      that 63 miRNAs were downregulated and 43 miRNAs were upregulated in serous
      ovarian cancer tissues compared with control tissues. The expression of five
      dysregulated miRNAs was validated using quantitative polymerase chain reaction
      (RT-qPCR). GO term and pathway analysis revealed that the biological process of
      the cell cycle was significantly enriched and the MAPK signaling pathway was
      highly involved in the progression of ovarian cancer. The results suggested that
      the aberrant expression of miRNAs is involved in ovarian carcinogenesis and thus
      these miRNAs may function as diagnostic and prognostic biomarkers.

PMID- 24939817
TI  - Dexamethasone pretreatment for 24 h versus 6 h for prevention of postextubation
      airway obstruction in children: a randomized double-blind trial.
AB  - PURPOSE: Multidose steroid pretreatment is effective in preventing postextubation
      airway obstruction (PEAO) in adults, however controversy continues for children.
      This study was designed as a randomized, placebo-controlled, double-blind trial
      to compare the effect of 24-h pretreatment with dexamethasone (24hPD) versus 6-h
      pretreatment (6hPD) on PEAO and reintubation in children at a tertiary care
      hospital in a developing economy. METHODS: Hundred twenty-four children (3 months
      to 12 years) intubated for >=48 h and planned to have extubation during next 24 h
      were randomized to receive 24hPD (0.5 mg/kg/dose, q6h, total of six doses; n =
      66) or 6hPD (total of three doses; n = 58). Patients with preexistent upper
      airway conditions, chronic respiratory diseases, steroid therapy in last 7 days,
      gastrointestinal bleeding, hypertension, and hyperglycemia and those likely to
      have poor airway reflexes were excluded. RESULTS: The two groups were similar at
      baseline. 24hPD reduced the incidence of PEAO (43/66 versus 48/58; p = 0.027)
      with absolute risk reduction of 17 %. It also reduced the incidence of
      reintubation, though nonsignificantly, by half [5/61 versus 9/58; relative risk
      (RR), 1.09; 95 % confidence interval (CI), 0.96-1.25]. Time to recovery from PEAO
      among non-reintubated patients was shorter among 24hPD patients (p = 0.016). No
      adverse event was noted with dexamethasone use. Intubation duration >7 days and
      cuffed tracheal tubes were found to be independent risk factors for PEAO (odds
      ratio 6 and 3.12, respectively). CONCLUSIONS: 24-h pretreatment with multidose
      dexamethasone reduced the incidence of PEAO and the time to recover from it.
      24hPD should be considered for high-risk children intubated for >48 h in the
      study setting. Further studies with larger sample size from different
      socioeconomic background are desirable to validate these findings.

PMID- 24939819
TI  - Asymmetric ozone oxidation of silylalkenes using a C2-symmetrical dialkoxysilyl
      group as a chiral auxiliary.
AB  - Ozone oxidation of silyl-substituted alkenes, namely silylalkenes, proceeds in an
      addition-type manner to afford alpha-silylperoxy carbonyl compounds in good to
      excellent yields, without the formation of normal ozonolysis products. Herein the
      ozone oxidation of chiral alkenylsilanes prepared from alkynes and a newly
      designed chiral hydrosilane is reported. The reaction affords silylperoxides with
      high diastereoselectivity (up to 94 % d.r.). The silylperoxides are convertible
      into enantioenriched chiral acyloins in a stereospecific manner. 

PMID- 24939818
TI  - Is prophylactic anti-resorptive therapy required in thyroid cancer patients
      receiving TSH-suppressive treatment with thyroxine?

PMID- 24939820
TI  - Improvement of the leukocyte differential performed by flow cytometry using the
      advanced 2.0 version of the CytoDiff CXP software.

PMID- 24939821
TI  - Can non-contrast-enhanced CT (NECT) triage patients suspected of having non
      traumatic acute aortic syndromes (AAS)?
AB  - This work was conducted to determine whether non-contrast-enhanced CT (NECT) of
      patients with suspected acute aortic syndrome (AAS) can identify patients with a
      very low likelihood of a positive diagnosis. In the derivation phase, patients
      who received both NECT and contrast-enhanced CT angiography (CTA) for suspected
      AAS were identified. Two readers blinded to CTA results analyzed NECTs from AAS
      positive and negative cases, recording maximal aortic diameters and qualitative
      findings of aortic disease. Logistic regression analysis was performed to
      identify independent positive predictors for AAS; those predictors were then used
      to create a decision rule. For the validation phase, NECTs from patients
      evaluated for AAS at a second institution were reviewed by two independent
      readers who recorded the presence of decision rule predictors while blinded to
      CTA results. In the derivation phase, 34 CTA positive and 83 CTA negative cases
      were reviewed. Measurements of aortic diameter alone achieved mean sensitivity
      and specificity of 82 % and of 83 %, respectively. Logistic regression identified
      aortic diameter, displaced calcifications, high attenuation aortic wall and
      abnormal aortic contour as independent predictors of AAS. The decision rule
      incorporating these findings achieved higher mean sensitivity (93 %), negative
      predictive value (96 %), and moderate reader agreement (kappa = 0.59). For the
      validation phase, application of the decision rule to 35 AAS positive and 45 AAS
      negative cases at the second institution yielded sensitivity of 100 % and
      specificity of 74 % for both readers. NECT can identify patients with a very low
      likelihood of AAS and potentially mitigate the urgency of performing CTA.

PMID- 24939822
TI  - Methylation patterns of estrogen receptor alpha promoter correlate with estrogen
      receptor alpha expression and clinicopathological factors in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the seventh most common type of cancer;
      notably, the incidence of HCC is four to eight times higher in men than women.
      Previous studies reported that the estrogen receptor (ER) signaling pathway is
      involved in the pathogenesis of HCC, although the extent of its involvement is
      unclear due to several conflicting reports. In the present study, tumor and
      paired adjacent non-cancerous tissues from 157 HCC patients were collected.
      Transcriptome sequencing and real-time quantitative polymerase chain reaction
      were used to quantify the ER alpha (ESR1) expression levels, and the Sequenom
      EpiTYPER assay was used to delineate the methylation patterns in the ESR1
      promoter. We found that ESR1 expression was significantly reduced in tumor
      tissues (P < 0.001) compared to adjacent non-cancerous tissues. The CpG sites
      around the transcription start site were significantly hypermethylated in the
      tumor (P < 0.0001). This methylation pattern also correlated with the gene
      expression (P < 0.0001). Additionally, we found that the hypermethylation of ESR1
      was associated with the presence of fibrous capsules (P = 1.2 * 10-4), the
      absence of microvascular invasions (P = 8.0 * 10-4), thin trabecular pattern (P =
      0.025), and lower histologic gradings (P = 5.2 * 10-3). Thus, ESR1 expression is
      a candidate tumor suppressor gene in HCC. Further, promoter hypermethylation may
      be a mechanism by which expression of ESR1 is repressed, and the extent of
      hypermethylation of ESR1 may be a marker for HCC status and progression.

PMID- 24939823
TI  - Jaceosidin, a natural flavone, promotes angiogenesis via activation of
      VEGFR2/FAK/PI3K/AKT/NF-kappaB signaling pathways in endothelial cells.
AB  - Angiogenesis, the growth of new blood vessels from pre-existing vasculature,
      plays an important role in physiological and pathological processes such as
      embryonic development wound healing and revascularization of tissues after
      exposure to ischemia. We investigated the effects of jaceosidin, a main
      constituent of medicinal herbs of the genus Artemisia, on angiogenesis and
      signaling pathways in endothelial cells. Jaceosidin stimulated proliferation,
      migration and tubulogenesis of ECs as well as ex vivo sprouting from aorta rings,
      which are phenomena typical of angiogenesis. Jaceosidin activated vascular
      endothelial growth factor receptor 2 (VEGFR2, FLk-1/KDR) and angiogenic signaling
      molecules such as focal adhesion kinase, phosphatidylinositol 3-kinase, and its
      downstream target, the serine-threonine kinase AKTWe also demonstrated that
      jaceosidin activated the NF-kappaB-driven expression of a luciferase reporter
      gene and NF-kappaB binding to DNA. Jaceosidin-induced proliferation and migration
      of human umbilical vascular endothelial cells were strongly inhibited by the
      phosphatidylinositol 3-kinase inhibitor LY294002 and NF-kappaB inhibitor BAY11
      7082, indicating that the PI3K/AKT/NF-kappaB signaling pathway is involved in
      jaceosidin-induced angiogenesis. Our results suggest that jaceosidin stimulates
      angiogenesis by activating the VEGFR2/FAK/PI3K/AKT/NF-kappaB signaling pathway
      and that it may be useful in developing angiogenic agents to promote the growth
      of collateral blood vessels in ischemic tissues. 

PMID- 24939824
TI  - Solving the puzzle of Parkinson's disease using induced pluripotent stem cells.
AB  - The prevalence and incidence of Parkinson's disease (PD) is increasing due to a
      prolonged life expectancy. This highlights the need for a better mechanistic
      understanding and new therapeutic approaches. However, traditional in vitro and
      in vivo experimental models to study PD are suboptimal, thus hampering the
      progress in the field. The epigenetic reprogramming of somatic cells to induced
      pluripotent stem cells (iPSCs) offers a unique way to overcome this problem, as
      these cells share many properties of embryonic stem cells (ESCs) including the
      potential to be transformed into different lineages. PD modeling with iPSCs is
      nowadays facilitated by the growing availability of high-efficiency neural
      specific differentiation protocols and the possibility to correct or induce
      mutations as well as creating marker cell lines using designer nucleases. These
      technologies, together with steady advances in human genetics, will likely
      introduce profound changes in the way we interpret PD and develop new treatments.
      Here, we summarize the different PD iPSCs reported so far and discuss the
      challenges for disease modeling using these cell lines.

PMID- 24939825
TI  - Dynamics of cocaine- and amphetamine-regulated transcript containing cell changes
      in the adrenal glands of two kidney, one clip rats.
AB  - Taking into consideration the homeostatic disorders resulting from renal
      hypertension and the essential role of cocaine- and amphetamine-regulated
      transcript (CART) in maintaining homeostasis by regulating many functions of the
      body, the question arises as to what extent the renovascular hypertension affects
      the morphology and dynamics of changes of CART-containing cells in the adrenal
      glands. The aim of the present study was to examine the distribution, morphology,
      and dynamics of changes of CART-containing cells in the adrenal glands of "two
      kidney, one clip" (2K1C) renovascular hypertension model in rats. The studies
      were carried out on the adrenal glands of rats after 3, 14, 28, 42, and 91 days
      from the renal artery clipping procedure. To identify neuroendocrine cells,
      immunohistochemical reaction was performed with the use of a specific antibody
      against CART. It was revealed that renovascular hypertension causes changes in
      the endocrine cells containing CART in the adrenal glands of rats. The changes
      observed in the endocrine cells depend on the time when the rats with
      experimentally induced hypertension were examined. In the first period of
      hypertension, the number and immunoreactivity of CART-containing cells were
      decreased, while from the 28-day test, it significantly increased, as compared to
      the control rats. CART is relevant to the regulation of homeostasis in the
      cardiovascular system and seems to be involved in renovascular hypertension. The
      results of the present work open the possibility of new therapeutic perspectives
      for the treatment of arterial hypertension, since CART function is involved in
      their pathophysiology. 

PMID- 24939826
TI  - Expression of MMP-2, MT1-MMP, and TIMP-2 by cultured rabbit corneal fibroblasts
      under mechanical stretch.
AB  - Refractive surgery not only leads to tissue injury but also evokes mechanical
      stress increase of the cornea. How the mechanical stress affects the corneal
      matrix remodeling, specifically, matrix metalloproteinases (MMPs) and their
      inhibitors (tissue inhibitors of metalloproteinases; TIMPs) is not well
      understood. In this study, cultured rabbit corneal fibroblasts in vitro were
      subjected to regimen of 5%, 10%, or 15% equibiaxial stretch at 0.1 Hz for 3 or 24
      h. MMP-2 protein level was measured by gelatin zymography and Western blotting.
      MMP-2, membrane type 1 MMP (MT1-MMP), and TIMP-2 mRNA levels were quantified by
      real-time quantitative PCR. Extracellular regulated protein kinase (ERK)
      phosphorylation protein levels were assessed by Western blotting. Our results
      showed that a 15% stretch resulted in increases in MMP-2 protein, MMP-2 mRNA, and
      MT1-MMP mRNA levels, but a decrease in TIMP-2 mRNA level. However, a 5% stretch
      caused decreases in MMP-2 protein and mRNA level, but an increase in TIMP-2 mRNA
      level, and no change in MT1-MMP mRNA level. A 15% stretch also caused a
      significant increase in ERK1/2 phosphorylation. Inhibition of the
      mitogenactivated protein kinase (MEK) pathway with PD98059 attenuated stretch
      induced increase in MMP-2 production and ERK activity. These results suggest that
      small-magnitude stretching may promote corneal matrix synthetic events, whereas
      large-magnitude stretching promotes corneal matrix degradation by changing the
      balance between MMPs and TIMPs in corneal fibroblasts. Large-magnitude stretch
      induced increase in pro-MMP-2 production was in an ERK-dependent manner.

PMID- 24939827
TI  - A model for lentigo maligna recurrence using melanocyte count as a predictive
      marker based upon logistic regression analysis of a blinded retrospective review.
AB  - BACKGROUND: The pre-malignant skin lesion lentigo maligna (LM) presents a
      particular challenge. Pathologists demonstrate poor diagnostic concordance and
      often struggle to assess whether excision margins are truly negative. This can
      lead to equivocal histology reports and a lack of clear guidance with which
      surgeons may rationalise their surgical management plans. Based upon the
      biological principle that tumour burden increases the chance of recurrence, we
      propose a shift in diagnostic paradigm, using melanocyte count (MC) at an
      excision margin to predict LM recurrence. METHODS: This retrospective study
      reviewed all cases of LM from a regional UK melanoma centre (1996-2011), to
      include 167 excisions, from 99 patients. Pathology slides were assessed for MC
      (blinded) at the most affected margin. Seven secondary markers of neoplasia were
      additionally evaluated. Logistic regression analysis was used to model the
      relationship between MC and recurrence. RESULTS: MC is a strong predictor of LM
      recurrence (p < 0.0001). A regression curve predicts risk for individual MCs,
      which may also be divided into three risk strata; low (0-11% [MC 0-20]),
      intermediate (15-89% [MC 21-30]), and high risk (92-100% [MC >= 31]). MC
      misclassified 0.6% of cases in the low and high risk groups compared with 21% for
      pathologists, who were also equivocal for 18% of excisions. MC's inter-rater
      concordance was high (>0.9). The secondary factors were all independently
      associated with recurrence, but failed to improve predictive ability
      supplementary to MC. CONCLUSIONS: MC confidently predicts LM recurrence and is
      more accurate and reliable, whilst also reducing the uncertainty of current
      pathology assessment. Risk estimates for any given MC can be easily charted using
      the regression curve graph, where confidence interval and risk group boundaries
      demonstrate the degree of certainty associated with any given prediction. This
      change in approach is congruent with tumour behaviour. A recurrence 'tipping
      point' corresponds to the sharp risk increase across the intermediate group's
      narrow band of MC.

PMID- 24939829
TI  - Facial reanimation with masseteric to facial nerve transfer: a three-dimensional
      longitudinal quantitative evaluation.
AB  - Facial paralysis is a severe pathological condition, negatively affecting
      patients' quality of life. The altered tone and mobility of the mimetic
      musculature provoke both functional and morphological deficits. In the present
      study, we longitudinally measured facial movements in 14 patients (21-69 years)
      affected by unilateral facial paralysis not lasting longer than 23 months. The
      patients were analyzed before and after surgical masseteric to facial nerve
      neurorrhaphy. Examinations were performed at least 3 months after they had
      clinically started to regain facial mimicry. The displacement of selected facial
      landmarks was measured using an optoelectronic three-dimensional motion analyzer
      during: maximum smile without clenching (pre- and postsurgery), maximum smile by
      clenching on their posterior teeth (only postsurgery), and spontaneous smile
      (recorded during the vision of a funny video in both examinations). Before facial
      surgery, in all smiles facial landmarks moved more in the healthy than in the
      paretic side; after surgery, the differences decreased for both reduction of the
      healthy-side motion, and increment of the paretic-side motion (motion ratio
      before 52%, after 87%, p < 0.05, Students' t-test). The ratio between the paretic
      and healthy-side total motion (asymmetry) did not modify for maximum and
      spontaneous smiles, but significantly increased for the maximum smiles made with
      teeth clenching (asymmetry before 32%, after 11%, p < 0.001). Spontaneous smiles
      were recorded only in a subset of patients, but their execution was modified by
      surgery, with more symmetrical movements of the rehabilitated-side landmarks
      (asymmetry before 33%, after 10%), and reduced motion of the healthy-side ones
      (motion ratio before 51%, after 83%). In conclusion, the significant asymmetry in
      the magnitude of facial movements that characterized the analyzed patients before
      surgery reduced after surgery, at least in those facial areas interested by the
      masseteric to facial nerve reanimation. 

PMID- 24939828
TI  - The effect of upper eyelid blepharoplasty on eyebrow position.
AB  - BACKGROUND: Although upper eyelid blepharoplasty is one of the most frequently
      performed facial plastic surgical procedures, there is no consensus of opinion
      about the effect of an upper eyelid blepharoplasty on the position of the
      eyebrows in a general population. OBJECTIVES: This study was undertaken to
      determine this effect and to investigate whether preoperative compensatory
      rhytidosis of the forehead may cause a significantly greater postoperative
      lowering of the eyebrows. METHODS: An evaluation of 140 consecutive patients with
      complaints of visual impairment was performed, who underwent an upper eyelid
      blepharoplasty. The position of the eyebrows was measured pre- and
      postoperatively at three positions for each eye. In addition, the role of
      compensatory rhytidosis on eyebrow position was determined by classifying
      horizontal forehead lines. RESULTS: The mean drop in eyebrow position for all
      patients ranged from 0.35% to 1.23%. In females (n = 126), there was no
      significant postoperative drop in eyebrow position. In males (n = 14), however,
      one out of six measured distances (centre of pupil, lateral iris and lateral
      canthus) displayed a significant lowering of the eyebrow (p = 0.005).
      CONCLUSIONS: Our results show that the position of the eyebrow is not lowered
      significantly after an upper eyelid blepharoplasty performed among women with
      dermatochalasis and functional complaints of visual impairment. Male patients
      showed a slight trend of lowering of the eyebrows postoperatively. Preoperative
      lifting of the eyebrows by means of frontalis muscle activity did not influence
      the position of the eyebrows postoperatively, although forehead lines did seem to
      diminish significantly.

PMID- 24939830
TI  - Mondor's disease after implant-based breast reconstruction. Report of three cases
      and review of the literature.

PMID- 24939832
TI  - Tuning the electronic coupling in cyclometalated diruthenium complexes through
      substituent effects: a correlation between the experimental and calculated
      results.
AB  - A common bridging ligand, 3,3',5,5'-tetrakis(N-methylbenzimidazol-2-yl)biphenyl,
      and four terpyridine terminal ligands with various substituents (amine, tolyl,
      nitro, and ester groups) have been used to synthesize ten cyclometalated
      diruthenium complexes 1(2+) -10(2+) . Among them, compounds 1(2+) -6(2+) are
      redox nonsymmetric, and others are symmetric. These complexes show two Ru(III/II)
      processes and an intervalence charge transfer (IVCT) transition in the one
      electron oxidized state. The potential separation (DeltaE) of 1(2+) -10(2+) has
      been correlated to the energy difference DeltaG(0) , the energy of the IVCT band
      Eop , and the ground-state delocalization coefficient alpha(2) . Time-dependent
      (TD)DFT calculations suggest that the absorptions in the visible region of 1(2+) 
      6(2+) are mainly associated with the metal-to-ligand charge-transfer transitions
      from both ruthenium ions and to both terminal ligands and the bridging ligand.
      However, the energies of these transitions vary significantly. DFT calculations
      have been performed on 1(2+) -6(2+) and 1(3+) -6(3+) to give information on the
      electronic structures and spin populations of the mixed-valent compounds. The
      TDDFT-predicted IVCT excitations reproduce well the experimental trends in
      transition energies. In addition, three monoruthenium complexes have been
      synthesized for a comparison study. 

PMID- 24939831
TI  - Smoking and glomus tumours.

PMID- 24939833
TI  - Exploring personalized searches using tag-based user profiles and resource
      profiles in folksonomy.
AB  - With the increase in resource-sharing websites such as YouTube and Flickr, many
      shared resources have arisen on the Web. Personalized searches have become more
      important and challenging since users demand higher retrieval quality. To achieve
      this goal, personalized searches need to take users' personalized profiles and
      information needs into consideration. Collaborative tagging (also known as
      folksonomy) systems allow users to annotate resources with their own tags, which
      provides a simple but powerful way for organizing, retrieving and sharing
      different types of social resources. In this article, we examine the limitations
      of previous tag-based personalized searches. To handle these limitations, we
      propose a new method to model user profiles and resource profiles in
      collaborative tagging systems. We use a normalized term frequency to indicate the
      preference degree of a user on a tag. A novel search method using such profiles
      of users and resources is proposed to facilitate the desired personalization in
      resource searches. In our framework, instead of the keyword matching or
      similarity measurement used in previous works, the relevance measurement between
      a resource and a user query (termed the query relevance) is treated as a fuzzy
      satisfaction problem of a user's query requirements. We implement a prototype
      system called the Folksonomy-based Multimedia Retrieval System (FMRS).
      Experiments using the FMRS data set and the MovieLens data set show that our
      proposed method outperforms baseline methods. 

PMID- 24939834
TI  - Liposomal gels for site-specific, sustained delivery of celecoxib: in vitro and
      in vivo evaluation.
AB  - The objective of this work was to evaluate liposome-containing gel formulations
      for the sustained, site-specific delivery of celecoxib (CXB). Liposomes composed
      of phosphadtidylcholine (and various amounts of cholesterol (Ch) were prepared
      using thin film hydration and characterized for encapsulation efficiency, vesicle
      size, and drug-excipient interaction using differential scanning calorimetry and
      Fourier-transform infrared spectroscopy. The selected liposome formulation was
      incorporated in different gel formulations: the Ch ratio affected the
      encapsulation efficiency of the drug, by increasing Ch ratio up until 1:1 the
      encapsulation efficiency increased. Further increasing the Ch ratio resulted in
      decreasing encapsulation efficiency. In vitro drug release and skin permeation
      studies showed sustained release and enhanced permeation compared with gel
      formulations containing free drug. In the rat paw edema test, the anti
      inflammatory activity of the selected liposomal gel formulation was higher and
      more sustained compared with that of the nonliposomal gel formulation containing
      free drug. These results suggest that the liposome-containing gels are promising
      formulations for sustained, site-specific delivery of CXB.

PMID- 24939835
TI  - Ecdysone signalling and ovarian development in insects: from stem cells to
      ovarian follicle formation.
AB  - Although a great deal of information is available concerning the role of ecdysone
      in insect oogenesis, research has tended to focus on vitellogenesis and
      choriogenesis. As such, the study of oogenesis in a strict sense has received
      much less attention. This situation changed recently when a number of
      observations carried out in the meroistic polytrophic ovarioles of Drosophila
      melanogaster started to unravel the key roles played by ecdysone in different
      steps of oogenesis. Thus, in larval stages, a non-autonomous role of ecdysone,
      first in repression and later in activation, of stem cell niche and primordial
      germ cell differentiation has been reported. In the adult, ecdysone stimulates
      the proliferation of germline stem cells, plays a role in stem cell niche
      maintenance and is needed non-cell-autonomously for correct differentiation of
      germline stem cells. Moreover, in somatic cells ecdysone is required for 16-cell
      cyst formation and for ovarian follicle development. In the transition from
      stages 8 to 9 of oogenesis, ecdysone signalling is fundamental when deciding
      whether or not to go ahead with vitellogenesis depending on the nutritional
      status, as well as to start border cell migration. This article is part of a
      Special Issue entitled: Nuclear receptors in animal development. 

PMID- 24939836
TI  - Vitamin D and its receptor during late development.
AB  - Expression of the vitamin D receptor (VDR) is widespread but may vary depending
      on the developmental stage of the animal, and therefore may differentially
      influence phenotypic function. Thus, the major role of the 1,25-dihydroxyvitamin
      D [1,25(OH)2D]/VDR system is to regulate mineral and skeletal homeostasis,
      although mainly after birth. Post-natally, under conditions of low dietary
      calcium, the 1,25(OH)2D/VDR system enhances intestinal transcellular transport of
      calcium and possibly paracellular calcium entry by regulating genes that are
      critical for these functions. This process, by providing adequate calcium, is
      essential for normal development of the skeletal growth plate and mineralization
      of bone. Furthermore, blood calcium and phosphorus homeostasis is maintained by
      an interplay between feedback loops of the 1,25(OH)2D/VDR system with parathyroid
      hormone and with fibroblast-growth factor (FGF) 23 respectively. The
      1,25(OH)2D/VDR system can also modulate the expression of genes involved in both
      bone formation and resorption post-natally. Ligand independent activity of the
      VDR normally influences mammalian hair cycling after birth by potentiating Wnt
      and bone morphogenetic protein (BMP) signaling. Nevertheless ligand bound VDR may
      also modulate epidermal cell proliferation/differentiation by regulating the
      balance in function of c-MYC and its antagonist the transcriptional repressor
      MAD1/MXD1 in skin epithelia. The 1,25(OH)2D/VDR system can also modulate innate
      immune cells and promote a more tolerogenic immunological status and may
      therefore influence inflammation and the development of autoimmunity; whether
      this impacts the fetus is uncertain. This article is part of a Special Issue
      entitled: Nuclear receptors in animal development. 

PMID- 24939837
TI  - GP who ran an out of hours locum service has most GMC charges dismissed.

PMID- 24939838
TI  - Inhibition of estradiol synthesis impairs fear extinction in male rats.
AB  - Emerging research has demonstrated that the sex hormone estradiol regulates fear
      extinction in female rodents and women. Estradiol may also regulate fear
      extinction in males, given its role in synaptic plasticity in both sexes. Here we
      report that inhibition of estradiol synthesis during extinction training, via the
      aromatase inhibitor fadrozole, significantly impairs extinction recall in male
      rats. This deficit in extinction recall is not due to state-dependent memory
      formation and is completely abolished by coadministration of estradiol. Our data
      suggest that estradiol may be just as important in the regulation of fear
      extinction in males as it is in females. 

PMID- 24939840
TI  - Multisite organic-inorganic hybrid catalysts for the direct sustainable synthesis
      of GABAergic drugs.
AB  - Multisite organic-inorganic hybrid catalysts have been prepared and applied in a
      new general, practical, and sustainable synthetic procedure toward industrially
      relevant GABA derivatives. The domino sequence is composed of seven chemical
      transformations which are performed in two one-pot reactions. The method produces
      both enantiomeric forms of the product in high enantiopurity as well as the
      racemate in good yields after a single column purification step. This protocol
      highlights major process intensification, catalyst recyclability, and low waste
      generation. 

PMID- 24939839
TI  - NMDA receptor- and ERK-dependent histone methylation changes in the lateral
      amygdala bidirectionally regulate fear memory formation.
AB  - It is well established that fear memory formation requires de novo gene
      transcription in the amygdala. We provide evidence that epigenetic mechanisms in
      the form of histone lysine methylation in the lateral amygdala (LA) are regulated
      by NMDA receptor (NMDAR) signaling and involved in gene transcription changes
      necessary for fear memory consolidation. Here we found increases in histone H3
      lysine 9 dimethylation (H3K9me2) levels in the LA at 1 h following auditory fear
      conditioning, which continued to be temporally regulated up to 25 h following
      behavioral training. Additionally, we demonstrate that inhibiting the H3K9me2
      histone lysine methyltransferase G9a (H/KMTs-G9a) in the LA impaired fear memory,
      while blocking the H3K9me2 histone lysine demethylase LSD1 (H/KDM-LSD1) enhanced
      fear memory, suggesting that H3K9me2 in the LA can bidirectionally regulate fear
      memory formation. Furthermore, we show that NMDAR activity differentially
      regulated the recruitment of H/KMT-G9a, H/KDM-LSD1, and subsequent H3K9me2 levels
      at a target gene promoter. This was largely regulated by GluN2B- but not GluN2A
      containing NMDARs via ERK activation. Moreover, fear memory deficits associated
      with NMDAR or ERK blockade were successfully rescued through pharmacologically
      inhibiting LSD1, suggesting that enhancements of H3K9me2 levels within the LA can
      rescue fear memory impairments that result from hypofunctioning NMDARs or loss of
      ERK signaling. Together, the present study suggests that histone lysine
      methylation regulation in the LA via NMDAR-ERK-dependent signaling is involved in
      fear memory formation. 

PMID- 24939841
TI  - Altered inhibition of Cx26 hemichannels by pH and Zn2+ in the A40V mutation
      associated with keratitis-ichthyosis-deafness syndrome.
AB  - Excessive opening of undocked Cx26 hemichannels in the plasma membrane is
      associated with disease pathogenesis in keratitis-ichthyosis-deafness (KID)
      syndrome. Thus far, excessive opening of KID mutant hemichannels has been
      attributed, almost solely, to aberrant inhibition by extracellular Ca(2+). This
      study presents two new possible contributing factors, pH and Zn(2+). Plasma pH
      levels and micromolar concentrations of Zn(2+) inhibit WT Cx26 hemichannels.
      However, A40V KID mutant hemichannels show substantially reduced inhibition by
      these factors. Using excised patches, acidification was shown to be effective
      from either side of the membrane, suggesting a protonation site accessible to
      H(+) flux through the pore. Sensitivity to pH was not dependent on extracellular
      aminosulfonate pH buffers. Single channel recordings showed that acidification
      did not affect unitary conductance or block the hemichannel but rather promoted
      gating to the closed state with transitions characteristic of the intrinsic loop
      gating mechanism. Examination of two nearby KID mutants in the E1 domain, G45E
      and D50N, showed no changes in modulation by pH or Zn(2+). N-bromo-succinimide,
      but not thiol-specific reagents, attenuated both pH and Zn(2+) responses.
      Individually mutating each of the five His residues in WT Cx26 did not reveal a
      key His residue that conferred sensitivity to pH or Zn(2+). From these data and
      the crystal structure of Cx26 that suggests that Ala-40 contributes to an
      intrasubunit hydrophobic core, the principal effect of the A40V mutation is
      probably a perturbation in structure that affects loop gating, thereby affecting
      multiple factors that act to close Cx26 hemichannels via this gating mechanism. 

PMID- 24939842
TI  - Histone cross-talk connects protein phosphatase 1alpha (PP1alpha) and histone
      deacetylase (HDAC) pathways to regulate the functional transition of bromodomain
      containing 4 (BRD4) for inducible gene expression.
AB  - Transcription elongation has been recognized as a rate-limiting step for the
      expression of signal-inducible genes. Through recruitment of positive
      transcription elongation factor P-TEFb, the bromodomain-containing protein BRD4
      plays critical roles in regulating the transcription elongation of a vast array
      of inducible genes that are important for multiple cellular processes. The
      diverse biological roles of BRD4 have been proposed to rely on its functional
      transition between chromatin targeting and transcription regulation. The
      signaling pathways and the molecular mechanism for regulating this transition
      process, however, are largely unknown. Here, we report a novel role of
      phosphorylated Ser(10) of histone H3 (H3S10ph) in governing the functional
      transition of BRD4. We identified that the acetylated lysines 5 and 8 of
      nucleosomal histone H4 (H4K5ac/K8ac) is the BRD4 binding site, and the protein
      phosphatase PP1alpha and class I histone deacetylase (HDAC1/2/3) signaling
      pathways are essential for the stress-induced BRD4 release from chromatin. In the
      unstressed state, phosphorylated H3S10 prevents the deacetylation of nucleosomal
      H4K5ac/K8ac by HDAC1/2/3, thereby locking up the majority of BRD4 onto chromatin.
      Upon stress, PP1alpha-mediated dephosphorylation of H3S10ph allows the
      deacetylation of nucleosomal H4K5ac/K8ac by HDAC1/2/3, thereby leading to the
      release of chromatin-bound BRD4 for subsequent recruitment of P-TEFb to enhance
      the expression of inducible genes. Therefore, our study revealed a novel
      mechanism that the histone cross-talk between H3S10ph and H4K5ac/K8ac connects
      PP1alpha and HDACs to govern the functional transition of BRD4. Combined with
      previous studies on the regulation of P-TEFb activation, the intricate signaling
      network for the tight control of transcription elongation is established. 

PMID- 24939843
TI  - A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis
      induced by oxidative stress.
AB  - The p75 neurotrophin receptor (p75(NTR)) mediates the death of specific
      populations of neurons during the development of the nervous system or after
      cellular injury. The receptor has also been implicated as a contributor to
      neurodegeneration caused by numerous pathological conditions. Because many of
      these conditions are associated with increases in reactive oxygen species, we
      investigated whether p75(NTR) has a role in neurodegeneration in response to
      oxidative stress. Here we demonstrate that p75(NTR) signaling is activated by 4
      hydroxynonenal (HNE), a lipid peroxidation product generated naturally during
      oxidative stress. Exposure of sympathetic neurons to HNE resulted in neurite
      degeneration and apoptosis. However, these effects were reduced markedly in
      neurons from p75(NTR-/-) mice. The neurodegenerative effects of HNE were not
      associated with production of neurotrophins and were unaffected by pretreatment
      with a receptor-blocking antibody, suggesting that oxidative stress activates
      p75(NTR) via a ligand-independent mechanism. Previous studies have established
      that proteolysis of p75(NTR) by the metalloprotease TNFalpha-converting enzyme
      and gamma-secretase is necessary for p75(NTR)-mediated apoptotic signaling.
      Exposure of sympathetic neurons to HNE resulted in metalloprotease- and gamma
      secretase-dependent cleavage of p75(NTR). Pharmacological blockade of p75(NTR)
      proteolysis protected sympathetic neurons from HNE-induced neurite degeneration
      and apoptosis, suggesting that cleavage of p75(NTR) is necessary for oxidant
      induced neurodegeneration. In vivo, p75(NTR-/-) mice exhibited resistance to
      axonal degeneration associated with oxidative injury following administration of
      the neurotoxin 6-hydroxydopamine. Together, these data suggest a novel mechanism
      linking oxidative stress to ligand-independent cleavage of p75(NTR), resulting in
      axonal fragmentation and neuronal death. 

PMID- 24939844
TI  - Inhibition of protein phosphatase 2A (PP2A) prevents Mcl-1 protein
      dephosphorylation at the Thr-163/Ser-159 phosphodegron, dramatically reducing
      expression in Mcl-1-amplified lymphoma cells.
AB  - Abundant, sustained expression of prosurvival Mcl-1 is an important determinant
      of viability and drug resistance in cancer cells. The Mcl-1 protein contains PEST
      sequences (enriched in proline, glutamic acid, serine, and threonine) and is
      normally subject to rapid turnover via multiple different pathways. One of these
      pathways involves a phosphodegron in the PEST region, where Thr-163
      phosphorylation primes for Ser-159 phosphorylation by glycogen synthase kinase-3.
      Turnover via this phosphodegron-targeted pathway is reduced in Mcl-1
      overexpressing BL41-3 Burkitt lymphoma and other cancer cells; turnover is
      further slowed in the presence of phorbol ester-induced ERK activation, resulting
      in Mcl-1 stabilization and an exacerbation of chemoresistance. The present
      studies focused on Mcl-1 dephosphorylation, which was also found to profoundly
      influence turnover. Exposure of BL41-3 cells to an inhibitor of protein
      phosphatase 2A (PP2A), okadaic acid, resulted in a rapid increase in
      phosphorylation at Thr-163 and Ser-159, along with a precipitous decrease in Mcl
      1 expression. The decline in Mcl-1 expression preceded the appearance of cell
      death markers and was not slowed in the presence of phorbol ester. Upon exposure
      to calyculin A, which also potently inhibits PP2A, versus tautomycin, which does
      not, only the former increased Thr-163/Ser-159 phosphorylation and decreased Mcl
      1 expression. Mcl-1 co-immunoprecipitated with PP2A upon transfection into CHO
      cells, and PP2A/Aalpha knockdown recapitulated the increase in Mcl-1
      phosphorylation and decrease in expression. In sum, inhibition of PP2A prevents
      Mcl-1 dephosphorylation and results in rapid loss of this prosurvival protein in
      chemoresistant cancer cells. 

PMID- 24939846
TI  - Targeting the ion channel Kv1.3 with scorpion venom peptides engineered for
      potency, selectivity, and half-life.
AB  - Ion channels are an attractive class of drug targets, but progress in developing
      inhibitors for therapeutic use has been limited largely due to challenges in
      identifying subtype selective small molecules. Animal venoms provide an
      alternative source of ion channel modulators, and the venoms of several species,
      such as scorpions, spiders and snails, are known to be rich sources of ion
      channel modulating peptides. Importantly, these peptides often bind to hyper
      variable extracellular loops, creating the potential for subtype selectivity
      rarely achieved with small molecules. We have engineered scorpion venom peptides
      and incorporated them in fusion proteins to generate highly potent and selective
      Kv1.3 inhibitors with long in vivo half-lives. Kv1.3 has been reported to play a
      role in human T cell activation, and therefore, these Kv1.3 inhibitor fusion
      proteins may have potential for the treatment of autoimmune diseases. Our results
      support an emerging approach to generating subtype selective therapeutic ion
      channel inhibitors. 

PMID- 24939845
TI  - Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain
      Tax protein.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell
      leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV
      1 transactivator protein Tax controls many critical cellular pathways, including
      host cell DNA damage response mechanisms, cell cycle progression, and apoptosis.
      Extracellular vesicles called exosomes play critical roles during pathogenic
      viral infections as delivery vehicles for host and viral components, including
      proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1
      infected cells contain unique host and viral proteins that may contribute to HTLV
      1-induced pathogenesis. We found exosomes derived from infected cells to contain
      Tax protein and proinflammatory mediators as well as viral mRNA transcripts,
      including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from
      HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome
      recipient cells when treated with Fas antibody. This survival was cFLIP
      dependent, with Tax showing induction of NF-kappaB in exosome-recipient cells.
      Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were
      protected from apoptosis through activation of AKT. Similar experiments with
      primary cultures showed protection and survival of peripheral blood mononuclear
      cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained
      more phosphorylated Rb, consistent with the role of Tax in regulation of the cell
      cycle. Collectively, these results suggest that exosomes may play an important
      role in extracellular delivery of functional HTLV-1 proteins and mRNA to
      recipient cells. 

PMID- 24939847
TI  - Post-translational transformation of methionine to aspartate is catalyzed by heme
      iron and driven by peroxide: a novel subunit-specific mechanism in hemoglobin.
AB  - A pathogenic V67M mutation occurs at the E11 helical position within the heme
      pockets of variant human fetal and adult hemoglobins (Hb). Subsequent post
      translational modification of Met to Asp was reported in gamma subunits of human
      fetal Hb Toms River (gamma67(E11)Val -> Met) and beta subunits of adult Hb (HbA)
      Bristol-Alesha (beta67(E11)Val -> Met) that were associated with hemolytic
      anemia. Using kinetic, proteomic, and crystal structural analysis, we were able
      to show that the Met -> Asp transformation involves heme cycling through its
      oxoferryl state in the recombinant versions of both proteins. The conversion to
      Met and Asp enhanced the spontaneous autoxidation of the mutants relative to wild
      type HbA and human fetal Hb, and the levels of Asp were elevated with increasing
      levels of hydrogen peroxide (H2O2). Using H2(18)O2, we verified incorporation of
      (18)O into the Asp carboxyl side chain confirming the role of H2O2 in the
      oxidation of the Met side chain. Under similar experimental conditions, there was
      no conversion to Asp at the alphaMet(E11) position in the corresponding HbA Evans
      (alpha62(E11)Val -> Met). The crystal structures of the three recombinant
      Met(E11) mutants revealed similar thioether side chain orientations. However, as
      in the solution experiments, autoxidation of the Hb mutant crystals leads to
      electron density maps indicative of Asp(E11) formation in beta subunits but not
      in alpha subunits. This novel post-translational modification highlights the
      nonequivalence of human Hb alpha, beta, and gamma subunits with respect to redox
      reactivity and may have direct implications to alpha/beta hemoglobinopathies and
      design of oxidatively stable Hb-based oxygen therapeutics.

PMID- 24939848
TI  - Control of the diadenylate cyclase CdaS in Bacillus subtilis: an autoinhibitory
      domain limits cyclic di-AMP production.
AB  - The Gram-positive bacterium Bacillus subtilis encodes three diadenylate cyclases
      that synthesize the essential signaling nucleotide cyclic di-AMP. The activities
      of the vegetative enzymes DisA and CdaA are controlled by protein-protein
      interactions with their conserved partner proteins. Here, we have analyzed the
      regulation of the unique sporulation-specific diadenylate cyclase CdaS. Very low
      expression of CdaS as the single diadenylate cyclase resulted in the appearance
      of spontaneous suppressor mutations. Several of these mutations in the cdaS gene
      affected the N-terminal domain of CdaS. The corresponding CdaS mutant proteins
      exhibited a significantly increased enzymatic activity. The N-terminal domain of
      CdaS consists of two alpha-helices and is attached to the C-terminal
      catalytically active diadenylate cyclase (DAC) domain. Deletion of the first or
      both helices resulted also in strongly increased activity indicating that the N
      terminal domain serves to limit the enzyme activity of the DAC domain. The
      structure of YojJ, a protein highly similar to CdaS, indicates that the protein
      forms hexamers that are incompatible with enzymatic activity of the DAC domains.
      In contrast, the mutations and the deletions of the N-terminal domain result in
      conformational changes that lead to highly increased enzymatic activity. Although
      the full-length CdaS protein was found to form hexamers, a truncated version with
      a deletion of the first N-terminal helix formed dimers with high enzyme activity.
      To assess the role of CdaS in sporulation, we assayed the germination of wild
      type and cdaS mutant spores. The results indicate that cyclic di-AMP formed by
      CdaS is required for efficient germination. 

PMID- 24939852
TI  - A proof-of-principle robot with potential for the development of a hand-held
      tactile instrument for minimally-invasive artery cross-clamping.
AB  - One of the most common diseases of the vascular system is abdominal aortic
      aneurysm (AAA), for which the most definitive treatment is surgery. Minimally
      invasive aorta surgery is a novel method of surgery performed through small
      incisions and offers significant advantages including less pain, shorter hospital
      stay, faster patient recovery, less possibility of infection, etc. However, lack
      of sense of touch is the main drawback of this type of aorta surgery that would
      incapacitate the surgeon to exactly distinguish the aorta from its surrounding
      tissues which could cause various problems during the aorta cross-clamping
      process. One of the most important drawbacks is that it makes the aorta cross
      clamping process the most time-consuming process of aortic repair surgery. The
      artificial tactile sensing approach is a novel method that can be used in various
      fields of medicine and, more specifically, in minimally invasive surgeries, where
      using the 'tactile sense' is not possible. In this paper, considering the present
      problems during aortic-repair-laparoscopy and imitating the movement of surgeons'
      fingers during aorta cross-clamping, a novel tactile-based artery cross-clamping
      robot is introduced and its function is evaluated experimentally. It is
      illustrated that this new tactile-based artery cross-clamping robot is well
      capable of dissecting an artery from its adjacent tissues in a short time with an
      acceptable accuracy.

PMID- 24939850
TI  - HIV-1 infection induces interleukin-1beta production via TLR8 protein-dependent
      and NLRP3 inflammasome mechanisms in human monocytes.
AB  - The induction of inflammatory cytokines such as IL-1beta is associated with the
      progression of human immunodeficiency virus, type 1 (HIV-1) disease or AIDS.
      Unlike most inflammatory cytokines that are regulated by NF-kappaB at the
      transcriptional level, production of mature IL-1beta also depends on inflammasome
      activation. The mechanism by which HIV-1 induces pro-IL-1beta expression and
      activates inflammasomes to cleave pro-IL-1beta into its bioactive form is not
      clearly defined. We report here that HIV-1 infection in human monocytes
      efficiently induced IL-1beta expression and inflammasome activation. Toll-like
      receptor 8 (TLR8) was required for inducing pro-IL-1beta expression, whereas the
      NLRP3 inflammasome was required for IL-1beta maturation and release. Furthermore,
      the lysosomal protease cathepsin B and HIV-1 induced production of reactive
      oxygen species were critical for HIV-induced inflammasome activation and IL-1beta
      production. HIV-1 entry, reverse transcription, and integration were all required
      for both pro-IL-1beta expression and inflammasome activation. Finally, we show
      that HIV-1-derived RNA was sufficient to induce both pro-IL-1beta expression and
      inflammasome activation. We conclude that HIV-1 infection induced the expression
      of pro-IL-1beta via TLR8-mediated mechanisms and activated caspase-1 through the
      NLRP3 inflammasome to cleave pro-IL-1beta into bioactive IL-1beta. These findings
      help to elucidate mechanisms of HIV-1 disease progression and identify novel
      targets for treating HIV-1 induced inflammation and immune activation. 

PMID- 24939849
TI  - Primary identification, biochemical characterization, and immunologic properties
      of the allergenic pollen cyclophilin cat R 1.
AB  - Cyclophilin (Cyp) allergens are considered pan-allergens due to frequently
      reported cross-reactivity. In addition to well studied fungal Cyps, a number of
      plant Cyps were identified as allergens (e.g. Bet v 7 from birch pollen, Cat r 1
      from periwinkle pollen). However, there are conflicting data regarding their
      antigenic/allergenic cross-reactivity, with no plant Cyp allergen structures
      available for comparison. Because amino acid residues are fairly conserved
      between plant and fungal Cyps, it is particularly interesting to check whether
      they can cross-react. Cat r 1 was identified by immunoblotting using allergic
      patients' sera followed by N-terminal sequencing. Cat r 1 (~ 91% sequence
      identity to Bet v 7) was cloned from a cDNA library and expressed in Escherichia
      coli. Recombinant Cat r 1 was utilized to confirm peptidyl-prolyl cis-trans
      isomerase (PPIase) activity by a PPIase assay and the allergenic property by an
      IgE-specific immunoblotting and rat basophil leukemia cell (RBL-SX38) mediator
      release assay. Inhibition-ELISA showed cross-reactive binding of serum IgE from
      Cat r 1-allergic individuals to fungal allergenic Cyps Asp f 11 and Mala s 6. The
      molecular structure of Cat r 1 was determined by NMR spectroscopy. The antigenic
      surface was examined in relation to its plant, animal, and fungal homologues. The
      structure revealed a typical cyclophilin fold consisting of a compact beta-barrel
      made up of seven anti-parallel beta-strands along with two surrounding alpha
      helices. This is the first structure of an allergenic plant Cyp revealing high
      conservation of the antigenic surface particularly near the PPIase active site,
      which supports the pronounced cross-reactivity among Cyps from various sources.

PMID- 24939853
TI  - Prototype electronic stethoscope vs. conventional stethoscope for auscultation of
      heart sounds.
AB  - In an effort to decrease the spread of hospital-acquired infections, many
      hospitals currently use disposable plastic stethoscopes in patient rooms. As an
      alternative, this study examines a prototype electronic stethoscope that does not
      break the isolation barrier between clinician and patient and may also improve
      the diagnostic accuracy of the stethoscope exam. This study aimed to investigate
      whether the new prototype electronic stethoscope improved auscultation of heart
      sounds compared to the standard conventional isolation stethoscope. In a
      controlled, non-blinded, cross-over study, clinicians were randomized to identify
      heart sounds with both the prototype electronic stethoscope and a conventional
      stethoscope. The primary outcome was the score on a 10-question heart sound
      identification test. In total, 41 clinicians completed the study. Subjects
      performed significantly better in the identification of heart sounds when using
      the prototype electronic stethoscope (median = 9 [7-10] vs. 8 [6-9] points, p
      value <0.0001). Subjects also significantly preferred the prototype electronic
      stethoscope. Clinicians using a new prototype electronic stethoscope achieved
      greater accuracy in identification of heart sounds and also universally favoured
      the new device, compared to the conventional stethoscope.

PMID- 24939851
TI  - Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER)
      stress-induced sensitization of p53-deficient human colon cancer cells to tumor
      necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated
      apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and
      celecoxib.
AB  - Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that
      triggers cell death upon binding to its ligand, TNF-related apoptosis-inducing
      ligand (TRAIL), and a combination of TRAIL and agents that increase the
      expression of DR5 is expected to be a novel anticancer therapy. In this report,
      we demonstrate that the stress response gene ATF3 is required for endoplasmic
      reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB)
      in human p53-deficient colorectal cancer cells. Both agents activated PERK
      eIF2alpha kinases and induced the expression of activating transcription factor 4
      (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were
      remarkably suppressed by reactive oxygen species scavengers. In the absence of
      ATF3, the induction of DR5 mRNA and protein was abrogated significantly, and this
      was associated with reduced cell death by cotreatment of TRAIL with ZER or CCB.
      By contrast, exogenous expression of ATF3 caused a more rapid and elevated
      expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by
      TRAIL/ZER or TRAIL/CCB. A reporter assay demonstrated that at least two ATF/cAMP
      response element motifs as well as C/EBP homologous protein motif at the proximal
      region of the human DR5 gene promoter were required for ZER-induced DR5 gene
      transcription. Taken together, our results provide novel insights into the role
      of ATF3 as an essential transcription factor for p53-independent DR5 induction
      upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL
      based anticancer therapy. 

PMID- 24939854
TI  - The impact of policy changes on consumer behaviour and alcohol consumption in
      Scania, Sweden 1999-2005.
AB  - AIMS: To analyse the hypothesis that a gradual deregulation of traveller
      allowances, starting in 2001 and ending in 2004, on alcoholic beverages changed
      consumer behaviours that ultimately led to an increase in alcohol consumption in
      southern Sweden between in 2005 compared with 1999. METHODS: The data for this
      general population random sample prospective cohort study with repeated
      measurements were collected in 1999 (T1) and in 2005 (T2) in the county of
      Scania, analysing the answers from 8612 individuals, who at T1 were alcohol
      consumers and 18-80 years old. RESULTS: Aggregate age-adjusted general mean
      alcohol consumption did not change significantly between T1 and T2. Significant
      downward changes were found in a number of demographical and socioeconomic sub
      groups. Generalized linear model analyses indicated that the uptake of buying
      alcohol from a private person was associated with significantly higher
      consumption (P < 0.001). No longer buying alcohol from a private person,
      consuming illicitly distilled spirits or buying alcohol abroad were significantly
      associated with lower consumption at follow-up. Interaction effects between
      changing consumer behaviours were also identified. CONCLUSION: The deregulation
      of the cross-border trade of alcohol into Sweden did not, within our sample, lead
      to an increase in consumption. There were, however, significant decreases in
      consumption levels within different socio-demographic sub-groups. In relation to
      changing consumer behaviours both upward and downward shifts in drinking trends
      were observed.

PMID- 24939857
TI  - The role of teachers in delivering education about respectful relationships:
      exploring teacher and student perspectives.
AB  - The focus of this article is a school-based respectful relationships (RRs) pilot
      project involving grade 8 and 9 students. The project sought to develop a primary
      prevention approach to gender-based violence (GBV) in Australia. Of particular
      concern is the curriculum delivery component of a whole school approach that was
      piloted over a 10-week period in four High Schools in Melbourne, Victoria in
      2010. Using data collected from teachers and students through survey, focus group
      interviews and student written reflections, the article identifies the key role
      of the teacher, the curriculum materials and the curriculum context in assisting
      teachers to teach about GBV. Although there was opposition to teaching
      specifically about GBV by some male teachers, the data indicate that this did not
      detract from teachers exploring these issues under a 'RRs' framework. Through
      'supported risk taking', and the adoption of participatory teaching approaches
      and affirming and inclusive classrooms, teachers and students ended up with a
      positive experience of teaching and learning about GBV. 

PMID- 24939856
TI  - The role of S100A14 in epithelial ovarian tumors.
AB  - S100A14 is an EF-hand calcium-binding protein that has been reported to be
      involved in the progression of many malignancies. However, its role in ovarian
      cancer has not yet been clarified. In this study, we investigated the
      significance of S100A14 expression in epithelial ovarian cancers (EOCs) as well
      as it's mechanism of action. On both RNA and protein levels, S100A14 was
      overexpressed in transformed cells. Immunohistochemical staining demonstrated
      that S100A14 expression was associated with advanced stage (P<0.001) and poor
      tumor grade (P<0.001). Moreover, S100A14 overexpression was an independent
      prognostic factor for overall survival (HR = 4.53, P = 0.029). We also
      investigated S100A14's functional role by employing lentiviral-mediated
      overexpression and knockdown in EOC cells. S100A14 overexpression promoted cell
      proliferation, tumorigenesis, migration, and invasion, whereas S100A14 knockdown
      inhibited these properties. TOV112D cells that overexpressed S100A14 also
      exhibited greater tumor growth potential in xenografted mice. S100A14 promoted
      such a malignant phenotype in EOC cells through the PI3K/Akt pathway. Taken
      together, our data indicate that S100A14 has a crucial role in EOC progression,
      and its overexpression is associated with poor prognosis. Further study of
      S100A14's molecular mechanisms may lead to the development of a novel therapeutic
      target for ovarian cancer. 

PMID- 24939855
TI  - Comparison of phosphatidylethanol results to self-reported alcohol consumption
      among young injection drug users.
AB  - AIMS: To test the value of phosphatidylethanol (PEth) as a biomarker for alcohol
      consumption among injecting drug users (IDUs). METHODS: As part of a longitudinal
      study of young IDUs, dried blood spots and self-reported alcohol by structured
      interview were collected at baseline. We compared self-reported alcohol use to
      detectable PEth (>=8 ng/ml) in the blood spots as well as the relationships
      between quantitative PEth results and quantity measures of alcohol consumption.
      RESULTS: There were strong associations between PEth and self-reported
      categorical measures of alcohol consumption (all P < 0.01). There was high
      specificity for reporting abstaining from alcohol; 94% of those who reported not
      consuming alcohol in the prior month tested negative for PEth. PEth was well
      correlated with measures of alcohol use (e.g. with reported number of days
      drinking in the prior month: Spearman r = 0.70 (P < 0.001)). CONCLUSIONS: The
      positive correlation of PEth with reported alcohol consumption suggests that PEth
      may be a useful marker in settings where alcohol consumption is difficult to
      assess, or to corroborate or invalidate self-reported measures of alcohol
      consumption.

PMID- 24939859
TI  - The Clinical Practice Guideline on diagnosis and treatment of hyponatraemia: a
      response from Otsuka Pharmaceutical Europe Ltd.

PMID- 24939860
TI  - Clinical Practice Guidelines on diagnosis and treatment of hyponatraemia:
      response to letter from Otsuka Ltd.

PMID- 24939862
TI  - [2+2+1] cycloadditions of bis(dialkylamino)acetylenes with SiI2(Idip): syntheses
      and reactivity studies of unprecedented 2,3,4,5-tetraamino-1 H-siloles.
AB  - A novel method for the synthesis of 1H-siloles is presented. It involves a
      [2+2+1] cycloaddition of the ynediamines R2N-C=C-NR2 (R = Me, Et) with SiI2(Idip)
      (Idip = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) to afford the orange
      colored, highly water-sensitive 1,1-diiodo-2,3,4,5-tetraamino-1H-siloles
      SiI2{C4(NR2)4} (1-I: R = Me; 2-I R = Et). Treatment of 2-I with an excess of
      SiBr4 afforded after I/Br exchange the 1,1-dibromo-1H-silole SiBr2{C4(NEt2)4} (2
      Br). The 1H-siloles 1-I, 2-I, and 2-Br were fully characterized and their
      molecular structures determined by single-crystal X-ray diffraction. The
      compounds feature a slightly twisted five-membered silacyclopenta-2,4-diene ring
      and a double/single C-C bond alternation in the diene fragment. Reaction of 2-I
      with the N-heterocyclic carbene IMe4 (IMe4 = 1,3,4,5-tetramethylimidazolin-2
      ylidene) leads, after displacement of the iodide groups, to the unprecedented
      diiodide salt [Si(IMe4)2{C4(NEt2)4}](I)2 (3), containing a 1H-silole dication
      with a four-coordinate Si(IV) center. The crystal structure of 3 reveals similar
      bonding characteristics for the dicationic 1H-silole to those of the neutral 1H
      siloles 1-I-2-Br. Two-electron reduction of 3 with C8K affords, after elimination
      of one IMe4 group, the thermolabile, carbene-stabilized 1-silacyclopentadien-1
      ylidene Si{C4(NEt2)4}(IMe4) (4), which was characterized by elemental analysis
      and (1)H, (13)C{(1)H}, and (29)Si{(1)H} NMR spectroscopies.

PMID- 24939858
TI  - Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5
      signaling in the nucleus accumbens.
AB  - Intermittent systemic exposure to psychostimulants leads to several forms of long
      lasting behavioral plasticity including nonassociative sensitization and
      associative conditioning. In the nucleus accumbens (NAcc), the protein
      serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) and its phosphorylation
      target, the guanine-nucleotide exchange factor kalirin-7 (Kal7), may contribute
      to the neuroadaptations underlying the formation of conditioned associations.
      Pharmacological inhibition of Cdk5 in the NAcc prevents the increases in
      dendritic spine density normally observed in this site following repeated
      cocaine. Mice lacking the Kal7 gene display similar effects. As increases in
      spine density may relate to the formation of associative memories and both Cdk5
      and Kal7 regulate the generation of spines following repeated drug exposure, we
      hypothesized that either inhibiting Cdk5 or preventing its phosphorylation of
      Kal7 in the NAcc may prevent the induction of drug conditioning. In the present
      experiments, blockade in rats of NAcc Cdk5 activity with roscovitine (40 nmol/0.5
      MUl/side) prior to each of 4 injections of amphetamine (1.5 mg/kg; i.p.)
      prevented the accrual of contextual locomotor conditioning but spared the
      induction of locomotor sensitization as revealed on tests conducted one week
      later. Similarly, transient viral expression in the NAcc exclusively during
      amphetamine exposure of a threonine-alanine mutant form of Kal7 [mKal7(T1590A)]
      that is not phosphorylated by Cdk5 also prevented the accrual of contextual
      conditioning and spared the induction of sensitization. These results indicate
      that signaling via Cdk5 and Kal7 in the NAcc is necessary for the formation of
      context-drug associations, potentially through the modulation of dendritic spine
      dynamics in this site. 

PMID- 24939864
TI  - Optically detected cross-relaxation spectroscopy of electron spins in diamond.
AB  - The application of magnetic resonance spectroscopy at progressively smaller
      length scales may eventually permit 'chemical imaging' of spins at the surfaces
      of materials and biological complexes. In particular, the negatively charged
      nitrogen-vacancy (NV(-)) centre in diamond has been exploited as an optical
      transducer for nanoscale nuclear magnetic resonance. However, the spectra of
      detected spins are generally broadened by their interaction with proximate
      paramagnetic NV(-) centres through coherent and incoherent mechanisms. Here we
      demonstrate a detection technique that can resolve the spectra of electron spins
      coupled to NV(-) centres, in this case, substitutional nitrogen and neutral
      nitrogen-vacancy centres in diamond, through optically detected cross-relaxation.
      The hyperfine spectra of these spins are a unique chemical identifier, suggesting
      the possibility, in combination with recent results in diamonds harbouring
      shallow NV(-) implants, that the spectra of spins external to the diamond can be
      similarly detected. 

PMID- 24939863
TI  - Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty:
      a systematic review.
AB  - In recent years, there has been an increasing interest in local infiltration
      analgesia (LIA) as a technique to control postoperative pain. We conducted a
      systematic review of randomized clinical trials investigating LIA for total knee
      arthroplasty (TKA) and total hip arthroplasty (THA) to evaluate the analgesic
      efficacy of LIA for early postoperative pain treatment. In addition, the
      analgesic efficacy of wound catheters and implications for length of hospital
      stay (LOS) were evaluated. Twenty-seven randomized controlled trials in 756
      patients operated on with THA and 888 patients operated on with TKA were selected
      for inclusion in the review. In THA, no additional analgesic effect of LIA
      compared with placebo was reported in trials with low risk of bias when a
      multimodal analgesic regimen was administered perioperatively. Compared with
      intrathecal morphine and epidural analgesia, LIA was reported to have similar or
      improved analgesic efficacy. In TKA, most trials reported reduced pain and
      reduced opioid requirements with LIA compared with a control group treated with
      placebo/no injection. Compared with femoral nerve block, epidural or intrathecal
      morphine LIA provided similar or improved analgesia in the early postoperative
      period but most trials had a high risk of bias due to different systemic
      analgesia between groups. Overall, the use of wound catheters for postoperative
      administration of local anaesthetic was not supported in the included trials, and
      LOS was not related to analgesic efficacy. Despite the many studies of LIA, final
      interpretation is hindered by methodological insufficiencies in most studies,
      especially because of differences in use of systemic analgesia between groups.
      However, LIA provides effective analgesia in the initial postoperative period
      after TKA in most randomized clinical trials even when combined with multimodal
      systemic analgesia. In contrast, LIA may have limited additional analgesic
      efficacy in THA when combined with a multimodal analgesic regimen. Postoperative
      administration of local anaesthetic in wound catheters did not provide additional
      analgesia when systemic analgesia was similar and LOS was not related to use of
      LIA with a fast-track set-up. 

PMID- 24939865
TI  - Patient dose map indications on interventional X-ray systems and validation with
      Gafchromic XR-RV3 film.
AB  - To help avoiding secondary effects of interventional procedures like skin damage,
      a dose map method has been developed to provide an indication of the local dose
      on a surface representative of individual patient shapes. To minimise user
      interactions, patient envelope shapes are automatically determined depending on
      simple patient data information. Local doses are calculated in 1-cm2 areas
      depending on the estimated air kerma, table and gantry positions and system
      settings, taking into account the table and mattress attenuations and estimated
      backscatter from the patient. These local doses are cumulated for each location
      of the patient envelope during the clinical procedure. To assess the accuracy of
      the method, Gafchromic XR-RV3 films have been used in several operating
      configurations. Good visual agreements on cumulated dose localisation were
      obtained within the 1-cm2 precision of the map and the dose values agreed within
      24.9 % accuracy. The resulting dose map method has been integrated into GE
      Healthcare X-Ray angiographic systems and should help in the management of the
      dose by the users during the procedure. 

PMID- 24939866
TI  - In silico analysis of cell cycle progression.

PMID- 24939868
TI  - Improvement of neurofeedback therapy for improved attention through facilitation
      of brain activity using local sinusoidal extremely low frequency magnetic field
      exposure.
AB  - Traditional neurofeedback (NF) is a training approach aimed at altering brain
      activity using electroencephalography (EEG) rhythms as feedback. In NF training,
      external factors such as the subjects' intelligence can have an effect. In
      contrast, a low-energy NF system (LENS) does not require conscious effort from
      the subject, which results in fewer attendance sessions. However, eliminating the
      subject role seems to eliminate an important part of the NF system. This study
      investigated the facilitating effect on the theta-to-beta ratio from NF training,
      using a local sinusoidal extremely low frequency magnetic field (LSELF-MF) versus
      traditional NF. Twenty-four healthy, intelligent subjects underwent 10 training
      sessions to enhance beta (15-18 Hz), and simultaneously inhibit theta (4-7 Hz)
      and high beta (22-30 Hz) activity, at the Cz point in a 3-boat-race video game.
      Each session consisted of 3 statuses, PRE, DURING, and POST. In the DURING
      status, the NF training procedure lasted 10 minutes. Subjects were led to believe
      that they would be exposed to a magnetic field during NF training; however, 16 of
      the subjects who were assigned to the experimental group were really exposed to
      45 Hz-360 uT LSELF-MF at Cz. For the 8 other subjects, only the coil was located
      at the Cz point with no exposure. The duty cycle of exposure was 40% (2-second
      exposure and 3-second pause). The results show that the theta-to-beta ratio in
      the DURING status of each group differs significantly from the PRE and POST
      statuses. Between-group analysis shows that the theta-to-beta ratio in the DURING
      status of the experimental group is significantly (P < .001) lower than in the
      sham group. The result shows the effect of LSELF-MF on NF training. 

PMID- 24939867
TI  - Early prediction of therapy responses and outcomes in breast cancer patients
      using quantitative ultrasound spectral texture.
AB  - Early alterations in textural characteristics of quantitative ultrasound spectral
      parametric maps, in conjunction with changes in their mean values, are
      demonstrated here, for the first time, to be capable of predicting ultimate
      clinical/pathologic responses of breast cancer patients to chemotherapy.
      Mechanisms of cell death, induced by chemotherapy within tumor, introduce
      morphological alterations in cancerous cells, resulting in measurable changes in
      tissue echogenicity. We have demonstrated that the development of such changes is
      reflected in early alterations in textural characteristics of quantitative
      ultrasound spectral parametric maps, followed by consequent changes in their mean
      values. The spectral/textural biomarkers derived on this basis have been
      demonstrated as non-invasive surrogates of breast cancer chemotherapy response.
      Particularly, spectral biomarkers sensitive to the size and concentration of
      acoustic scatterers could predict treatment response of patients with up to 80%
      of sensitivity and specificity (p=0.050), after one week within 3-4 months of
      chemotherapy. However, textural biomarkers characterizing heterogeneities in
      distribution of acoustic scatterers, could differentiate between treatment
      responding and non-responding patients with up to 100% sensitivity and 93%
      specificity (p=0.002). Such early prediction permits offering effective
      alternatives to standard treatment, or switching to a salvage therapy, for
      refractory patients. 

PMID- 24939869
TI  - Three dimensional reconstruction of a CT angiogram of the left upper arm vessels.

PMID- 24939870
TI  - Fatty acid-binding protein 4, a point of convergence for angiogenic and metabolic
      signaling pathways in endothelial cells.
AB  - Fatty acid-binding protein 4 (FABP4) is an adipogenic protein and is implicated
      in atherosclerosis, insulin resistance, and cancer. In endothelial cells, FABP4
      is induced by VEGFA, and inhibition of FABP4 blocks most of the VEGFA effects. We
      investigated the DLL4-NOTCH-dependent regulation of FABP4 in human umbilical vein
      endothelial cells by gene/protein expression and interaction analyses following
      inhibitor treatment and RNA interference. We found that FABP4 is directly induced
      by NOTCH. Stimulation of NOTCH signaling with human recombinant DLL4 led to FABP4
      induction, independently of VEGFA. FABP4 induction by VEGFA was reduced by
      blockade of DLL4 binding to NOTCH or inhibition of NOTCH signal transduction.
      Chromatin immunoprecipitation of the NOTCH intracellular domain showed increased
      binding to two specific regions in the FABP4 promoter. The induction of FABP4
      gene expression was dependent on the transcription factor FOXO1, which was
      essential for basal expression of FABP4, and FABP4 up-regulation following
      stimulation of the VEGFA and/or the NOTCH pathway. Thus, we show that the DLL4
      NOTCH pathway mediates endothelial FABP4 expression. This indicates that
      induction of the angiogenesis-restricting DLL4-NOTCH can have pro-angiogenic
      effects via this pathway. It also provides a link between DLL4-NOTCH and FOXO1
      mediated regulation of endothelial gene transcription, and it shows that DLL4
      NOTCH is a nodal point in the integration of pro-angiogenic and metabolic
      signaling in endothelial cells. This may be crucial for angiogenesis in the tumor
      environment. 

PMID- 24939871
TI  - Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor
      tissue and their mutagenicity in human urothelial cells.
AB  - Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components
      in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental
      contaminants, can cause bladder tumor in rat models. Their role in TS related BC
      has not been forthcoming. To establish the relationship between acrolein and 4
      ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA
      adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT),
      and measured their mutagenicity in human urothelial cells. We found that the
      acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct
      levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM.
      Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5
      fold more mutagenic than the latter. These two types of DNA adducts induce
      different mutational signatures and spectra. We found that acrolein inhibits
      nucleotide excision and base excision repair and induces repair protein
      degradation in urothelial cells. Since acrolein is abundant in TS, inhaled
      acrolein is excreted into urine and accumulates in the bladder and because
      acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we
      propose that acrolein is a major bladder carcinogen in TS. 

PMID- 24939872
TI  - Prediction errors to emotional expressions: the roles of the amygdala in social
      referencing.
AB  - Social referencing paradigms in humans and observational learning paradigms in
      animals suggest that emotional expressions are important for communicating
      valence. It has been proposed that these expressions initiate stimulus
      reinforcement learning. Relatively little is known about the role of emotional
      expressions in reinforcement learning, particularly in the context of social
      referencing. In this study, we examined object valence learning in the context of
      a social referencing paradigm. Participants viewed objects and faces that turned
      toward the objects and displayed a fearful, happy or neutral reaction to them,
      while judging the gender of these faces. Notably, amygdala activation was larger
      when the expressions following an object were less expected. Moreover, when
      asked, participants were both more likely to want to approach, and showed
      stronger amygdala responses to, objects associated with happy relative to objects
      associated with fearful expressions. This suggests that the amygdala plays two
      roles in social referencing: (i) initiating learning regarding the valence of an
      object as a function of prediction errors to expressions displayed toward this
      object and (ii) orchestrating an emotional response to the object when value
      judgments are being made regarding this object. 

PMID- 24939873
TI  - Temporal changes in hepatic antioxidant enzyme activities after ischemia and
      reperfusion in a rat liver ischemia model: effect of dietary fish oil.
AB  - This study investigated the hypothesis that administration of tilapia fish oil
      diet would attenuate warm liver ischemia/reperfusion injury (IRI) and whether
      fish oil modulates prooxidant/antioxidant status. Male Wistar rats were subjected
      to 30 min of approximately 70% hepatic ischemia followed by 1, 12, and 24 h
      reperfusion. Rats were randomly divided into three groups: sham-operated group
      (SO), control-warm hepatic ischemia (WI) group, and Oil-WI group given tilapia
      oil for 3 weeks followed by liver IRI. Aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) levels were measured in the plasma. Levels of
      thiobarbituric acid reactive substances (TBARS) and antioxidant enzymes as
      superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)
      activities were measured in liver fractions. In the sham group, there was no
      enzymatic or histological change. I/R caused significant increase in serum AST,
      ALT, and tissue TBARS levels. As compared to the control group, animals treated
      with tilapia oil experienced a significant decrease (p < 0.05) in AST and ALT
      levels in reperfusion periods. Tissue TBARS levels in Oil-WI group were
      significantly (p < 0.05) reduced as compared to control group at 60 min after
      reperfusion. After ischemia, 1, 12, and 24 h of reperfusion, CAT, SOD, and GPx
      values were the lowest in the Oil-WI group and highest in the control group and
      were statistically significant (p < 0.05). Histological analysis also revealed
      that fish oil provided some protection compared with the control group. Tilapia
      oil exerts a protective effect during the early phase of reperfusion, and it
      modulates prooxidant/antioxidant status of rat liver subjected to warm IRI. 

PMID- 24939874
TI  - Obstructive sleep apnoea.

PMID- 24939875
TI  - piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3
      mark in germ cells.
AB  - Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose
      a constant threat to genomic integrity. This threat is particularly critical in
      germ cells, as changes in the genome that are induced by TEs will be transmitted
      to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize
      and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon
      repression correlates with establishment of CpG DNA methylation on their
      sequences, yet the mechanism and the spectrum of genomic targets of piRNA
      silencing are unknown. Here we show that in addition to DNA methylation, the
      piRNA pathway is required to maintain a high level of the repressive H3K9me3
      histone modification on long interspersed nuclear elements (LINEs) in germ cells.
      piRNA-dependent chromatin repression targets exclusively full-length elements of
      actively transposing LINE families, demonstrating the remarkable ability of the
      piRNA pathway to recognize active elements among the large number of genomic
      transposon fragments. 

PMID- 24939879
TI  - Communicating about family health history: heredity, culture, iatrogenesis and
      the public good.

PMID- 24939876
TI  - Evolutionally dynamic L1 regulation in embryonic stem cells.
AB  - Mobile elements are important evolutionary forces that challenge genomic
      integrity. Long interspersed element-1 (L1, also known as LINE-1) is the only
      autonomous transposon still active in the human genome. It displays an unusual
      pattern of evolution, with, at any given time, a single active L1 lineage
      amplifying to thousands of copies before getting replaced by a new lineage,
      likely under pressure of host restriction factors, which act notably by silencing
      L1 expression during early embryogenesis. Here, we demonstrate that in human
      embryonic stem (hES) cells, KAP1 (KRAB [Kruppel-associated box domain]-associated
      protein 1), the master cofactor of KRAB-containing zinc finger proteins (KRAB
      ZFPs) previously implicated in the restriction of endogenous retroviruses,
      represses a discrete subset of L1 lineages predicted to have entered the
      ancestral genome between 26.8 million and 7.6 million years ago. In mice, we
      documented a similar chronologically conditioned pattern, albeit with a much
      contracted time scale. We could further identify an L1-binding KRAB-ZFP,
      suggesting that this rapidly evolving protein family is more globally responsible
      for L1 recognition. KAP1 knockdown in hES cells induced the expression of KAP1
      bound L1 elements, but their younger, human-specific counterparts (L1Hs) were
      unaffected. Instead, they were stimulated by depleting DNA methyltransferases,
      consistent with recent evidence demonstrating that the PIWI-piRNA (PIWI
      interacting RNA) pathway regulates L1Hs in hES cells. Altogether, these data
      indicate that the early embryonic control of L1 is an evolutionarily dynamic
      process and support a model in which newly emerged lineages are first suppressed
      by DNA methylation-inducing small RNA-based mechanisms before KAP1-recruiting
      protein repressors are selected. 

PMID- 24939878
TI  - Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in
      carbon nanotube-driven tumorigenesis.
AB  - Cancer stem cells (CSCs) may represent targets for carcinogenic initiation by
      chemical and environmental agents. Recent studies have raised a concern over the
      potential carcinogenicity of carbon nanotubes (CNTs), one of the most commonly
      used engineered nanomaterials with asbestos-like properties. Here, we show that
      chronic (6-month) exposure of human lung epithelial cells to single-walled (SW)
      CNTs at the workplace-relevant concentration induced an emergence of lung CSCs,
      as indicated by the induction of CSC tumor spheres and side population (SP).
      These CSCs, which were found to overexpress tumor promoter caveolin-1 (Cav-1),
      displayed aggressive cancer phenotypes of apoptosis resistance and enhanced cell
      invasion and migration compared with their non-CSC counterpart. Using gene
      manipulation strategies, we reveal for the first time that Cav-1 plays an
      essential role in CSC regulation and aggressiveness of SWCNT-transformed cells
      partly through p53 dysregulation, consistent with their suggested role by
      microarray and gene ontology analysis. Cav-1 not only promoted tumorigenesis in a
      xenograft mouse model but also metastasis of the transformed cells to neighboring
      tissues. Since CSCs are crucial to the initiation and early development of
      carcinogenesis, our findings on CSC induction by SWCNTs and Cav-1 could aid in
      the early detection and risk assessment of the disease. 

PMID- 24939884
TI  - Alcohol charities may be influenced by funding from industry, research shows.

PMID- 24939880
TI  - Chemopreventive and chemotherapeutic effect of dietary supplementation of vitamin
      D on cholangiocarcinoma in a Chemical-Induced animal model.
AB  - Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D, a pro
      hormone, is getting popular due to its hormone-like functions after converted to
      its active form, 1alpha,25(OH)2D3. Here, we show that dietary supplementation
      with 6 IU/g of vitamin D greatly suppressed ICC initiation and progression
      without apparent toxicity in a chemically induced rat model. Microarray analysis
      of rat ICC tissues showed vitamin D supplementation modulated the expressions of
      several unique genes, including lipocalin 2 (Lcn2), confirmed by RT-qPCR and
      immunohistochemical (IHC) staining. Further, 53 of 80 human ICC specimens (66%)
      exhibited high LCN2 expression and LCN2 knockdown in SNU308 cells decreased cell
      growth and migration, suggesting LCN2 be an oncogene in human ICC. As human ICC
      SNU1079 cells were treated by 1alpha,25(OH)2D3, LCN2 expression and cell
      proliferation were attenuated. The downregulation of LCN2 expression was blunted
      when vitamin D receptor (VDR) was knocked down, implicating that the in vivo Lcn2
      downregulation is a direct consequence of vitamin D supplementation Our results
      support the prevailing concept that vitamin D status is negatively associated
      with cancer incidence and mortality and suggest LCN2 may be a potential target
      against ICC. Further studies of application of vitamin D or its analog against
      ICC are warranted. 

PMID- 24939881
TI  - Dysconnectivity within the default mode in first-episode schizophrenia: a
      stochastic dynamic causal modeling study with functional magnetic resonance
      imaging.
AB  - We report the first stochastic dynamic causal modeling (sDCM) study of effective
      connectivity within the default mode network (DMN) in schizophrenia. Thirty-three
      patients (9 women, mean age = 25.0 years, SD = 5) with a first episode of
      psychosis and diagnosis of schizophrenia--according to the Diagnostic and
      Statistic Manual of Mental Disorders, 4th edition, revised criteria--were
      studied. Fifteen healthy control subjects (4 women, mean age = 24.6 years, SD =
      4) were included for comparison. All subjects underwent resting state functional
      magnetic resonance imaging (fMRI) interspersed with 2 periods of continuous
      picture viewing. The anterior frontal (AF), posterior cingulate (PC), and the
      left and right parietal nodes of the DMN were localized in an unbiased fashion
      using data from 16 independent healthy volunteers (using an identical fMRI
      protocol). We used sDCM to estimate directed connections between and within nodes
      of the DMN, which were subsequently compared with t tests at the between subject
      level. The excitatory effect of the PC node on the AF node and the inhibitory
      self-connection of the AF node were significantly weaker in patients (mean values
      = 0.013 and -0.048 Hz, SD = 0.09 and 0.05, respectively) relative to healthy
      subjects (mean values = 0.084 and -0.088 Hz, SD = 0.15 and 0.77, respectively; P
      < .05). In summary, sDCM revealed reduced effective connectivity to the AF node
      of the DMN--reflecting a reduced postsynaptic efficacy of prefrontal afferents-
      in patients with first-episode schizophrenia.

PMID- 24939883
TI  - Depression and adherence to lifestyle changes in type 2 diabetes: a systematic
      review.
AB  - PURPOSE: Depression affects millions of people worldwide and is prevalent among
      those with diabetes. The purpose of this review was to synthesize recent research
      on depression and adherence to dietary and physical activity recommendations in
      persons with type 2 diabetes (T2DM). METHODS: This systematic review is a
      subanalysis of an NIH-funded model-testing meta-analysis. Thirteen electronic
      databases were searched using terms: depression, adherence, T2DM, diabetes.
      Selected studies: were reported in English between 2000 and 2012, focused on
      adults with T2DM, and measured depression and dietary and/or physical activity
      adherence. RESULTS: Twenty-seven studies involving 7266 participants were
      selected; participants were 54% female and 62 years of age, on average. When
      reported, depression prevalence in study samples ranged from 4.5% to 74%. Six
      intervention studies targeted diabetes treatment, with or without depression
      treatment; no studies focused solely on treating depression. Twenty-one
      descriptive studies examined relationships between depression and diet/physical
      activity adherence, finding a negative association. Only 2 of the 6 intervention
      studies examined this relationship; findings were inconsistent. CONCLUSION:
      Depression was associated with lower adherence to diabetes self-care, as
      evidenced primarily by descriptive studies; results of intervention studies were
      conflicting. Future research should focus on the effects of treating depression
      on diabetes health outcomes.

PMID- 24939882
TI  - Ban on television advertising of online medical services is lifted.

PMID- 24939885
TI  - Recovery of the gut microbiome following fecal microbiota transplantation.
AB  - Clostridium difficile infection is one of the most common health care-associated
      infections, and up to 40% of patients suffer from recurrence of disease following
      standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has
      been successfully used to treat recurrent C. difficile infection. It is
      hypothesized that FMT aids in recovery of a microbiota capable of colonization
      resistance to C. difficile. However, it is not fully understood how this occurs.
      Here we investigated changes in the fecal microbiota structure following FMT in
      patients with recurrent C. difficile infection, and imputed a hypothetical
      functional profile based on the 16S rRNA profile using a predictive metagenomic
      tool. Increased relative abundance of Bacteroidetes and decreased abundance of
      Proteobacteria were observed following FMT. The fecal microbiota of recipients
      following transplantation was more diverse and more similar to the donor profile
      than the microbiota prior to transplantation. Additionally, we observed
      differences in the imputed metagenomic profile. In particular, amino acid
      transport systems were overrepresented in samples collected prior to
      transplantation. These results suggest that functional changes accompany
      microbial structural changes following this therapy. Further identification of
      the specific community members and functions that promote colonization resistance
      may aid in the development of improved treatment methods for C. difficile
      infection. IMPORTANCE: Within the last decade, Clostridium difficile infection
      has surpassed other bacterial infections to become the leading cause of
      nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its
      capability in providing colonization resistance against C. difficile, is a known
      risk factor in C. difficile infection. In particular, recurrent C. difficile
      remains difficult to treat with standard antibiotic therapy. Fecal microbiota
      transplantation (FMT) has provided a successful treatment method for some
      patients with recurrent C. difficile infection, but its mechanism and long-term
      effects remain unknown. Our results provide insight into the structural and
      potential metabolic changes that occur following FMT, which may aid in the
      development of new treatment methods for C. difficile infection.

PMID- 24939887
TI  - The characterization of RNA viruses in tropical seawater using targeted PCR and
      metagenomics.
AB  - Viruses have a profound influence on the ecology and evolution of plankton, but
      our understanding of the composition of the aquatic viral communities is still
      rudimentary. This is especially true of those viruses having RNA genomes. The
      limited data that have been published suggest that the RNA virioplankton is
      dominated by viruses with positive-sense, single-stranded (+ss) genomes that have
      features in common with those of eukaryote-infecting viruses in the order
      Picornavirales (picornavirads). In this study, we investigated the diversity of
      the RNA virus assemblages in tropical coastal seawater samples using targeted PCR
      and metagenomics. Amplification of RNA-dependent RNA polymerase (RdRp) genes from
      fractions of a buoyant density gradient suggested that the distribution of two
      major subclades of the marine picornavirads was largely congruent with the
      distribution of total virus-like RNA, a finding consistent with their proposed
      dominance. Analyses of the RdRp sequences in the library revealed the presence of
      many diverse phylotypes, most of which were related only distantly to those of
      cultivated viruses. Phylogenetic analysis suggests that there were hundreds of
      unique picornavirad-like phylotypes in one 35-liter sample that differed from one
      another by at least as much as the differences among currently recognized
      species. Assembly of the sequences in the metagenome resulted in the
      reconstruction of six essentially complete viral genomes that had features
      similar to viruses in the families Bacillarna-, Dicistro-, and Marnaviridae.
      Comparison of the tropical seawater metagenomes with those from other habitats
      suggests that +ssRNA viruses are generally the most common types of RNA viruses
      in aquatic environments, but biases in library preparation remain a possible
      explanation for this observation. IMPORTANCE: Marine plankton account for much of
      the photosynthesis and respiration on our planet, and they influence the cycling
      of carbon and the distribution of nutrients on a global scale. Despite the
      fundamental importance of viruses to plankton ecology and evolution, most of the
      viruses in the sea, and the identities of their hosts, are unknown. This report
      is one of very few that delves into the genetic diversity within RNA-containing
      viruses in the ocean. The data expand the known range of viral diversity and shed
      new light on the physical properties and genetic composition of RNA viruses in
      the ocean.

PMID- 24939886
TI  - Capsule growth in Cryptococcus neoformans is coordinated with cell cycle
      progression.
AB  - The fungal pathogen Cryptococcus neoformans has several virulence factors, among
      which the most important is a polysaccharide capsule. The size of the capsule is
      variable and can increase significantly during infection. In this work, we
      investigated the relationship between capsular enlargement and the cell cycle.
      Capsule growth occurred primarily during the G1 phase. Real-time visualization of
      capsule growth demonstrated that this process occurred before the appearance of
      the bud and that capsule growth arrested during budding. Benomyl, which arrests
      the cells in G2/M, inhibited capsule growth, while sirolimus (rapamycin)
      addition, which induces G1 arrest, resulted in cells with larger capsule.
      Furthermore, we have characterized a mutant strain that lacks a putative G1/S
      cyclin. This mutant showed an increased capacity to enlarge the capsule, both in
      vivo (using Galleria mellonella as the host model) and in vitro. In the absence
      of Cln1, there was a significant increase in the production of extracellular
      vesicles. Proteomic assays suggest that in the cln1 mutant strain, there is an
      upregulation of the glyoxylate acid cycle. Besides, this cyclin mutant is
      avirulent at 37 degrees C, which correlates with growth defects at this
      temperature in rich medium. In addition, the cln1 mutant showed lower
      intracellular replication rates in murine macrophages. We conclude that cell
      cycle regulatory elements are involved in the modulation of the expression of the
      main virulence factor in C. neoformans. IMPORTANCE: Cryptococcus neoformans is a
      pathogenic fungus that has significant incidence worldwide. Its main virulence
      factor is a polysaccharide capsule that can increase in size during infection. In
      this work, we demonstrate that this process occurs in a specific phase of the
      cell cycle, in particular, in G1. In agreement, mutants that have an abnormal
      longer G1 phase show larger capsule sizes. We believe that our findings are
      relevant because they provide a link between capsule growth, cell cycle
      progression, and virulence in C. neoformans that reveals new aspects about the
      pathogenicity of this fungus. Moreover, our findings indicate that cell cycle
      elements could be used as antifungal targets in C. neoformans by affecting both
      the growth of the cells and the expression of the main virulence factor of this
      pathogenic yeast.

PMID- 24939890
TI  - Genetic diversity and population history of the endangered killifish Aphanius
      baeticus.
AB  - The secondary freshwater fish fauna of the western-Iberian Peninsula basin is
      primarily restricted to local coastal streams, and man-made salt evaporation
      ponds, etc., which are susceptible to periodical flood and drought events.
      Despite its uniqueness in ecological adaptation to high saltwater tolerance, very
      little is known about this fauna's population dynamics and evolutionary history.
      The killifish, Aphanius baeticus (Cyprinodontidae) is an endemic species
      restricted to river basins on Spain's southern Atlantic coastline, considered as
      "Endangered." In this study, the genetic structure, diversity and historical
      demography of A. baeticus were analyzed using mitochondrial (cytochrome b, N=131)
      and nuclear (4 out of 19 microsatellites tested, N=288) markers across its
      distribution range. The phylogenetic and networking reconstruction revealed
      subtle phylogeographic structuring. A scattered expansion at the beginning of the
      interglacial periods, coupled with posterior events of extinction and
      colonization caused by periodical cycles of flooding, could explain the absence
      of well-defined phylogenetic relationships among populations. Moreover, very low
      genetic diversity values and a weak population differentiation were detected. We
      proposed that dispersals allowed by periodic floods connecting river drainages
      may have promoted a wide genetic exchange among populations and could have
      contributed to the current genetic relatedness of these populations.

PMID- 24939889
TI  - Standards for sequencing viral genomes in the era of high-throughput sequencing.
AB  - Thanks to high-throughput sequencing technologies, genome sequencing has become a
      common component in nearly all aspects of viral research; thus, we are
      experiencing an explosion in both the number of available genome sequences and
      the number of institutions producing such data. However, there are currently no
      common standards used to convey the quality, and therefore utility, of these
      various genome sequences. Here, we propose five "standard" categories that
      encompass all stages of viral genome finishing, and we define them using simple
      criteria that are agnostic to the technology used for sequencing. We also provide
      genome finishing recommendations for various downstream applications, keeping in
      mind the cost-benefit trade-offs associated with different levels of finishing.
      Our goal is to define a common vocabulary that will allow comparison of genome
      quality across different research groups, sequencing platforms, and assembly
      techniques. 

PMID- 24939888
TI  - Evidence of extensive DNA transfer between bacteroidales species within the human
      gut.
AB  - The genome sequences of intestinal Bacteroidales strains reveal evidence of
      extensive horizontal gene transfer. In vitro studies of Bacteroides and other
      bacteria have addressed mechanisms of conjugative transfer and some phenotypic
      outcomes of these DNA acquisitions in the recipient, such as the acquisition of
      antibiotic resistance. However, few studies have addressed the horizontal
      transfer of genetic elements between bacterial species coresident in natural
      microbial communities, especially microbial ecosystems of humans. Here, we
      examine the genomes of Bacteroidales species from two human adults to identify
      genetic elements that were likely transferred among these Bacteroidales while
      they were coresident in the intestine. Using seven coresident Bacteroidales
      species from one individual and eight from another, we identified five large
      chromosomal regions, each present in a minimum of three of the coresident strains
      at near 100% DNA identity. These five regions are not found in any other
      sequenced Bacteroidetes genome at this level of identity and are likely all
      integrative conjugative elements (ICEs). Such highly similar and unique regions
      occur in only 0.4% of phylogenetically representative mock communities, providing
      strong evidence that these five regions were transferred between coresident
      strains in these subjects. In addition to the requisite proteins necessary for
      transfer, these elements encode proteins predicted to increase fitness, including
      orphan DNA methylases that may alter gene expression, fimbriae synthesis proteins
      that may facilitate attachment and the utilization of new substrates, putative
      secreted antimicrobial molecules, and a predicted type VI secretion system
      (T6SS), which may confer a competitive ecological advantage to these strains in
      their complex microbial ecosystem. IMPORTANCE: By analyzing Bacteroidales strains
      coresident in the gut microbiota of two human adults, we provide strong evidence
      for extensive interspecies and interfamily transfer of integrative conjugative
      elements within the intestinal microbiota of individual humans. In the recipient
      strain, we show that the conjugative elements themselves can be modified by the
      transposition of insertion sequences and retroelements from the recipient's
      genome, with subsequent transfer of these modified elements to other members of
      the microbiota. These data suggest that the genomes of our gut bacteria are
      substantially modified by other, coresident members of the ecosystem, resulting
      in highly personalized Bacteroidales strains likely unique to that individual.
      The genetic content of these ICEs suggests that their transfer from successful
      adapted members of an ecosystem confers beneficial properties to the recipient,
      increasing its fitness and allowing it to better compete within its particular
      personalized gut microbial ecosystem.

PMID- 24939892
TI  - Spontaneous background pathology in Gottingen minipigs.
AB  - The Gottingen minipig is gaining increasing popularity as a nonrodent species in
      nonclinical testing. The Gottingen minipig is easy to handle; has many anatomical
      and physiological similarities to man; and causes fewer ethical concerns than
      usage of the traditional nonrodent species, nonhuman primates, and dogs. The
      increasing usage of the Gottingen minipig has raised the need of appropriate
      background data. This article summarizes the background pathology of 835
      untreated control Gottingen minipigs of both sexes used at CiToxLAB Scantox A/S
      during the period of 1995 to 2007. 

PMID- 24939894
TI  - The kinase LMTK3 promotes invasion in breast cancer through GRB2-mediated
      induction of integrin beta1.
AB  - Lemur tyrosine kinase 3 (LMTK3) is associated with cell proliferation and
      endocrine resistance in breast cancer. We found that, in cultured breast cancer
      cell lines, LMTK3 promotes the development of a metastatic phenotype by inducing
      the expression of genes encoding integrin subunits. Invasive behavior in various
      breast cancer cell lines positively correlated with the abundance of LMTK3.
      Overexpression of LMTK3 in a breast cancer cell line with low endogenous LMTK3
      abundance promoted actin cytoskeleton remodeling, focal adhesion formation, and
      adhesion to collagen and fibronectin in culture. Using SILAC (stable isotope
      labeling by amino acids in cell culture) proteomic analysis, we found that LMTK3
      increased the abundance of integrin subunits alpha5 and beta1, encoded by ITGA5
      and ITGB1. This effect depended on the CDC42 Rho family guanosine triphosphatase,
      which was in turn activated by the interaction between LMTK3 and growth factor
      receptor-bound protein 2 (GRB2), an adaptor protein that mediates receptor
      tyrosine kinase-induced activation of RAS and downstream signaling. Knockdown of
      GRB2 suppressed LMTK3-induced CDC42 activation, blocked ITGA5 and ITGB1
      expression promoted by the transcription factor serum response factor (SRF), and
      reduced invasive activity. Furthermore, abundance of LMTK3 positively correlated
      with that of the integrin beta1 subunit in breast cancer patient's tumors. Our
      findings suggest a role for LMTK3 in promoting integrin activity during breast
      cancer progression and metastasis.

PMID- 24939891
TI  - Molecular analysis of Oryza latifolia Desv. (CCDD genome)-derived introgression
      lines and identification of value-added traits for rice (O. sativa L.)
      improvement.
AB  - Oryza latifolia is a tetraploid wild Oryza species with a CCDD genome that has
      been reported to harbor resistance to bacterial blight (BB), brown planthopper,
      and whitebacked planthopper. Aside from these traits, O. latifolia is also being
      tapped as a new source of resistance to lodging and high biomass production. To
      explore the genetic potential of O. latifolia as a novel genetic resource for the
      improvement of existing O. sativa cultivars, 27 disomic derivatives of O.
      latifolia monosomic alien addition lines (MAAL) were characterized for alien
      chromosome segment introgressions and evaluated for yield components, BB
      resistance, and strong stem characteristics. A total of 167 simple sequence
      repeat, sequence tagged site, and single nucleotide polymorphism markers, along
      with newly developed indel markers that were specifically designed to detect O.
      latifolia chromosome segment introgressions in an O. sativa background, were used
      to define alien introgressions in 27 disomics derived from O. latifolia MAALs.
      Genotype data showed that 32 unique introgressions spanning 0.31-22.73 Mb were
      introgressed in different combinations in each of the 27 disomic derivatives.
      Evaluation of the disomic derivatives for agronomic traits identified lines with
      putative QTLs for resistance to Philippine races 3A, 4, 9A, and 9D of BB.
      Putative quantitative trait loci (QTLs) conferring strong stem in 19 out of the
      27 disomic derivatives studied were also identified from O. latifolia
      introgressions on chromosome 6.

PMID- 24939893
TI  - A FAK-Cas-Rac-lamellipodin signaling module transduces extracellular matrix
      stiffness into mechanosensitive cell cycling.
AB  - Tissue and extracellular matrix (ECM) stiffness is transduced into intracellular
      stiffness, signaling, and changes in cellular behavior. Integrins and several of
      their associated focal adhesion proteins have been implicated in sensing ECM
      stiffness. We investigated how an initial sensing event is translated into
      intracellular stiffness and a biologically interpretable signal. We found that a
      pathway consisting of focal adhesion kinase (FAK), the adaptor protein p130Cas
      (Cas), and the guanosine triphosphatase Rac selectively transduced ECM stiffness
      into stable intracellular stiffness, increased the abundance of the cell cycle
      protein cyclin D1, and promoted S-phase entry. Rac-dependent intracellular
      stiffening involved its binding partner lamellipodin, a protein that transmits
      Rac signals to the cytoskeleton during cell migration. Our findings establish
      that mechanotransduction by a FAK-Cas-Rac-lamellipodin signaling module converts
      the external information encoded by ECM stiffness into stable intracellular
      stiffness and mechanosensitive cell cycling. Thus, lamellipodin is important not
      only in controlling cellular migration but also for regulating the cell cycle in
      response to mechanical signals. 

PMID- 24939895
TI  - The flavoprotein Mcap0476 (RlmFO) catalyzes m5U1939 modification in Mycoplasma
      capricolum 23S rRNA.
AB  - Efficient protein synthesis in all organisms requires the post-transcriptional
      methylation of specific ribosomal ribonucleic acid (rRNA) and transfer RNA (tRNA)
      nucleotides. The methylation reactions are almost invariably catalyzed by enzymes
      that use S-adenosylmethionine (AdoMet) as the methyl group donor. One noteworthy
      exception is seen in some bacteria, where the conserved tRNA methylation at m5U54
      is added by the enzyme TrmFO using flavin adenine dinucleotide together with
      N5,N10-methylenetetrahydrofolate as the one-carbon donor. The minimalist
      bacterium Mycoplasma capricolum possesses two homologs of trmFO, but surprisingly
      lacks the m5U54 tRNA modification. We created single and dual deletions of the
      trmFO homologs using a novel synthetic biology approach. Subsequent analysis of
      the M. capricolum RNAs by mass spectrometry shows that the TrmFO homolog encoded
      by Mcap0476 specifically modifies m5U1939 in 23S rRNA, a conserved methylation
      catalyzed by AdoMet-dependent enzymes in all other characterized bacteria. The
      Mcap0476 methyltransferase (renamed RlmFO) represents the first folate-dependent
      flavoprotein seen to modify ribosomal RNA.

PMID- 24939897
TI  - The elusive evidence for chromothripsis.
AB  - The chromothripsis hypothesis suggests an extraordinary one-step catastrophic
      genomic event allowing a chromosome to 'shatter into many pieces' and reassemble
      into a functioning chromosome. Recent efforts have aimed to detect chromothripsis
      by looking for a genomic signature, characterized by a large number of
      breakpoints (50-250), but a limited number of oscillating copy number states (2
      3) confined to a few chromosomes. The chromothripsis phenomenon has become widely
      reported in different cancers, but using inconsistent and sometimes relaxed
      criteria for determining rearrangements occur simultaneously rather than
      progressively. We revisit the original simulation approach and show that the
      signature is not clearly exceptional, and can be explained using only progressive
      rearrangements. For example, 3.9% of progressively simulated chromosomes with 50
      55 breakpoints were dominated by two or three copy number states. In addition, by
      adjusting the parameters of the simulation, the proposed footprint appears more
      frequently. Lastly, we provide an algorithm to find a sequence of progressive
      rearrangements that explains all observed breakpoints from a proposed
      chromothripsis chromosome. Thus, the proposed signature cannot be considered a
      sufficient proof for this extraordinary hypothesis. Great caution should be
      exercised when labeling complex rearrangements as chromothripsis from genome
      hybridization and sequencing experiments. 

PMID- 24939896
TI  - Two cationic porphyrin isomers showing different multimeric G-quadruplex
      recognition specificity against monomeric G-quadruplexes.
AB  - Ligands that can interact specifically with telomeric multimeric G-quadruplexes
      could be developed as promising anticancer drugs with few side effects related to
      other G-quadruplex-forming regions. In this paper, a new cationic porphyrin
      derivative, m-TMPipEOPP, was synthesized and characterized. Its multimeric G
      quadruplex recognition specificity under molecular crowding conditions was
      compared to its isomer p-TMPipEOPP. The slight structural difference accounts for
      different multimeric G-quadruplex recognition specificity for the two isomers. p
      TMPipEOPP can barely discriminate between multimeric and monomeric G
      quadruplexes. By contrast, m-TMPipEOPP can bind with multimeric but not with
      monomeric G-quadruplexes. p-TMPipEOPP might bind to multimeric G-quadruplexes by
      two modes: sandwich-like end-stacking mode and pocket-dependent intercalative
      mode. Increasing the pocket size between adjacent two G-quadruplex units is
      beneficial for the latter mode. m-TMPipEOPP might bind to multimeric G
      quadruplexes by a side binding mode, which confers m-TMPipEOPP with higher
      multimeric G-quadruplex recognition specificity compared to p-TMPipEOPP. m
      TMPipEOPP increases the stability of multimeric G-quadruplex under both dilute
      and molecular crowding conditions but its G-quadruplex-stabilizing ability is a
      little weaker than p-TMPipEOPP. These results provide important information for
      the design of highly specific multimeric G-quadruplex ligands. Another
      interesting finding is that pocket size is an important factor in determining the
      stability of multimeric G-quadruplexes.

PMID- 24939900
TI  - Engineered TAL Effector modulators for the large-scale gain-of-function
      screening.
AB  - Recent effective use of TAL Effectors (TALEs) has provided an important approach
      to the design and synthesis of sequence-specific DNA-binding proteins. However,
      it is still a challenging task to design and manufacture effective TALE
      modulators because of the limited knowledge of TALE-DNA interactions. Here we
      synthesized more than 200 TALE modulators and identified two determining factors
      of transcription activity in vivo: chromatin accessibility and the distance from
      the transcription start site. The implementation of these modulators in a gain-of
      function screen was successfully demonstrated for four cell lines in
      migration/invasion assays and thus has broad relevance in this field.
      Furthermore, a novel TALE-TALE modulator was developed to transcriptionally
      inhibit target genes. Together, these findings underscore the huge potential of
      these TALE modulators in the study of gene function, reprogramming of cellular
      behaviors, and even clinical investigation. 

PMID- 24939898
TI  - Structural studies of CNG repeats.
AB  - CNG repeats (where N denotes one of the four natural nucleotides) are abundant in
      the human genome. Their tendency to undergo expansion can lead to hereditary
      diseases known as TREDs (trinucleotide repeat expansion disorders). The toxic
      factor can be protein, if the abnormal gene is expressed, or the gene transcript,
      or both. The gene transcripts have attracted much attention in the biomedical
      community, but their molecular structures have only recently been investigated.
      Model RNA molecules comprising CNG repeats fold into long hairpins whose stems
      generally conform to an A-type helix, in which the non-canonical N-N pairs are
      flanked by C-G and G-C pairs. Each homobasic pair is accommodated in the helical
      context in a unique manner, with consequences for the local helical parameters,
      solvent structure, electrostatic potential and potential to interact with
      ligands. The detailed three-dimensional profiles of RNA CNG repeats can be used
      in screening of compound libraries for potential therapeutics and in structure
      based drug design. Here is a brief survey of the CNG structures published to
      date. 

PMID- 24939899
TI  - Conjugation with polyamines enhances the antibacterial and anticancer activity of
      chloramphenicol.
AB  - Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only
      use in developed countries because of its potential toxicity. To explore the
      influence of polyamines on the uptake and activity of CAM into cells, a series of
      polyamine-CAM conjugates were synthesized. Both polyamine architecture and the
      position of CAM-scaffold substitution were crucial in augmenting the
      antibacterial and anticancer potency of the synthesized conjugates. Compounds 4
      and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid
      attached to N4 and N1 positions of N(8),N(8)-dibenzylspermidine, respectively,
      exhibited higher activity than CAM in inhibiting the puromycin reaction in a
      bacterial cell-free system. Kinetic and footprinting analysis revealed that
      whereas the CAM-scaffold preserved its role in competing with the binding of
      aminoacyl-tRNA 3'-terminus to ribosomal A-site, the polyamine-tail could
      interfere with the rotatory motion of aminoacyl-tRNA 3'-terminus toward the P
      site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved
      antibacterial activity, particularly against CAM-resistant strains. Compound 4
      also possessed enhanced toxicity against human cancer cells, and lower toxicity
      against healthy human cells. Thus, the designed conjugates proved to be suitable
      tools in investigating the ribosomal catalytic center plasticity and some of them
      exhibited greater efficacy than CAM itself. 

PMID- 24939901
TI  - A gain-of-function mouse model identifies PRMT6 as a NF-kappaB coactivator.
AB  - Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that modifies
      histone tails. To help elucidate the biological function of PRMT6 in vivo, we
      generated transgenic mice that ubiquitously express PRMT6 fused to the hormone
      binding portion of the estrogen receptor (ER*). The ER*-PRMT6 fusion is unstable
      and cytoplasmic, but upon systemic treatment with tamoxifen, it becomes
      stabilized and translocates into the nucleus. As a result, a dramatic increase in
      the H3R2me2a histone mark is observed. We found that one consequence of induced
      ER*-PRMT6 activation is increased IL-6 levels. IL-6 expression is regulated by
      the nuclear factor-kappa B (NF-kappaB) transcription factor, and PRMT6 functions
      as a coactivator of this pathway. We show that PRMT6 directly interacts with
      RelA, and that its overexpression enhances the transcriptional activity of an
      ectopic NF-kappaB reporter and endogenously regulates NF-kappaB target genes.
      PRMT6 is recruited, by RelA, to selective NF-kappaB target promoters upon TNF
      alpha stimulation. Moreover, ER*-PRMT6 activation causes RelA accumulation in the
      nucleus. In summary, we observe that PRMT6 is recruited to chromatin at selective
      NF-kappaB target promoters, where it likely impacts the histone code and/or
      methylates other chromatin-associated proteins to facilitate transcription. 

PMID- 24939904
TI  - What do zebrafish want? Impact of social grouping, dominance and gender on
      preference for enrichment.
AB  - Although environmental enrichment is known to improve laboratory rodent wellbeing
      and enhance scientific data collection, relatively little is known with regards
      to the type of enrichment that might be useful for zebrafish (Danio rerio).
      Therefore, this study explored if zebrafish displayed preferences for a range of
      enrichments, including substrates, artificial plants, combinations thereof and
      airstones. Tanks divided into two compartments containing different enrichment
      cues were used to determine the preferences of zebrafish housed in pairs and
      groups of eight. When comparing time spent in enriched versus barren
      compartments, dominant individuals in a pair displayed a preference for substrate
      and behaviourally excluded the subordinate (p < 0.05). In groups there was a
      preference for all substrate (p < 0.01) and plant (p < 0.05) enrichments over
      barren conditions. The strongest preference was for gravel substrate and images
      of gravel attached to the bottom of the tank. When preferences were compared for
      different enrichments, gravel (both sexes, p < 0.01) again emerged as the cue
      attracting the most significant preferences, with any combination featuring
      gravel substrate preferred over any combination featuring sand (p < 0.05). The
      study has demonstrated that zebrafish reared in barren conditions preferred
      structural enrichment over standard conditions; however, when fish were held in
      pairs this was influenced by dominance status and in groups this was influenced
      by gender.

PMID- 24939902
TI  - CBP and p300 acetylate PCNA to link its degradation with nucleotide excision
      repair synthesis.
AB  - The proliferating cell nuclear antigen (PCNA) protein serves as a molecular
      platform recruiting and coordinating the activity of factors involved in multiple
      deoxyribonucleic acid (DNA) transactions. To avoid dangerous genome instability,
      it is necessary to prevent excessive retention of PCNA on chromatin. Although
      PCNA functions during DNA replication appear to be regulated by different post
      translational modifications, the mechanism regulating PCNA removal and
      degradation after nucleotide excision repair (NER) is unknown. Here we report
      that CREB-binding protein (CBP), and less efficiently p300, acetylated PCNA at
      lysine (Lys) residues Lys13,14,77 and 80, to promote removal of chromatin-bound
      PCNA and its degradation during NER. Mutation of these residues resulted in
      impaired DNA replication and repair, enhanced the sensitivity to ultraviolet
      radiation, and prevented proteolytic degradation of PCNA after DNA damage.
      Depletion of both CBP and p300, or failure to load PCNA on DNA in NER deficient
      cells, prevented PCNA acetylation and degradation, while proteasome inhibition
      resulted in accumulation of acetylated PCNA. These results define a CBP and p300
      dependent mechanism for PCNA acetylation after DNA damage, linking DNA repair
      synthesis with removal of chromatin-bound PCNA and its degradation, to ensure
      genome stability. 

PMID- 24939903
TI  - Mosquito and Drosophila entomobirnaviruses suppress dsRNA- and siRNA-induced
      RNAi.
AB  - RNA interference (RNAi) is a crucial antiviral defense mechanism in insects,
      including the major mosquito species that transmit important human viruses. To
      counteract the potent antiviral RNAi pathway, insect viruses encode RNAi
      suppressors. However, whether mosquito-specific viruses suppress RNAi remains
      unclear. We therefore set out to study RNAi suppression by Culex Y virus (CYV), a
      mosquito-specific virus of the Birnaviridae family that was recently isolated
      from Culex pipiens mosquitoes. We found that the Culex RNAi machinery processes
      CYV double-stranded RNA (dsRNA) into viral small interfering RNAs (vsiRNAs).
      Furthermore, we show that RNAi is suppressed in CYV-infected cells and that the
      viral VP3 protein is responsible for RNAi antagonism. We demonstrate that VP3 can
      functionally replace B2, the well-characterized RNAi suppressor of Flock House
      virus. VP3 was found to bind long dsRNA as well as siRNAs and interfered with
      Dicer-2-mediated cleavage of long dsRNA into siRNAs. Slicing of target RNAs by
      pre-assembled RNA-induced silencing complexes was not affected by VP3. Finally,
      we show that the RNAi-suppressive activity of VP3 is conserved in Drosophila X
      virus, a birnavirus that persistently infects Drosophila cell cultures. Together,
      our data indicate that mosquito-specific viruses may encode RNAi antagonists to
      suppress antiviral RNAi. 

PMID- 24939905
TI  - Anaesthetic effects in the ferret of alfaxalone alone and in combination with
      medetomidine or tramadol: a pilot study.
AB  - Alfaxalone is a neurosteroid with anaesthetic effects and it has been used
      successfully in several animal species. However, there are no data, to our
      knowledge, about its efficacy and safety in ferrets (Mustela putorius furo). We
      evaluated a variety of anaesthetic regimens in ferrets, namely, alfaxalone at 20,
      10 and 5 mg/kg (n = 1, 10 and 9, respectively; intravenously); medetomidine at 20
      ug/kg (n = 3; intramuscularly); medetomidine (20 ug/kg, intramuscularly) plus
      alfaxalone (2.5 mg/kg, intravenously; n = 7); and tramadol (5 mg/kg,
      intramuscularly) plus alfaxalone (5 mg/kg, intravenously; n = 2). Two animals
      treated with alfaxalone at 10 mg/kg and 20 mg/kg, respectively, died. At 5 mg/kg
      alfaxalone produced anaesthesia with a similar onset but a shorter duration of
      anaesthesia and analgesia than alfaxalone at 10 mg/kg. The medetomidine
      alfaxalone combination produced anaesthesia and analgesia of a longer duration
      than alfaxalone administered alone at 5 mg/kg (P < 0.0001 and P < 0.001,
      respectively). Under this anaesthetic regimen, there was a progressive decrease
      in pulse rate during the first 30 min before the pulse rate stabilized.
      Respiratory parameters were maintained at acceptable levels. When tramadol was
      administered, all the animals exhibited a strong excitation reaction and in no
      case was the toe-pinch reflex clearly abolished. Thus, alfaxalone plus
      medetomidine provided safe and effective anaesthesia in ferrets. Alfaxalone,
      alone or in combination with tramadol, did not produce satisfactory results for
      use as an anaesthetic for this species.

PMID- 24939908
TI  - Incorporating pathology in the practice of infectious disease: myths and reality.
AB  - The role pathology plays in establishing or excluding infectious diseases has
      been established. However, as the practice of pathology has become
      subspecialized, there is not enough infectious disease specimen volume to have a
      pathologist dedicated full time to this crosscutting subspecialty. So, what are
      the myths and realities of a practicing infectious disease pathologist in the
      hospital setting? Infectious disease clinicians tend to consult pathologists when
      there are questions regarding terminology used in pathology reports; when there
      is the need to perform additional studies on formalin-fixed, paraffin-embedded
      tissues; and when there is an interest in seeing biopsies or resections obtained
      from patients and in obtaining photographs for presentations. Pathologists
      consult infectious disease pathologists when there is a need to review diverse
      inflammatory reactions; for identification of fungi, parasites, or unknown
      structures; to define the need to use special stains and other techniques in
      order to identify organisms in tissues that have been formalin fixed; and to help
      with terminology to be used in reports. This review explores in more detail why
      and how these consultations occur. 

PMID- 24939907
TI  - Evidence after imputation for a role of MICA variants in nonprogression and elite
      control of HIV type 1 infection.
AB  - Past genome-wide association studies (GWAS) involving individuals with AIDS have
      mainly identified associations in the HLA region. Using the latest software, we
      imputed 7 million single-nucleotide polymorphisms (SNPs)/indels of the 1000
      Genomes Project from the GWAS-determined genotypes of individuals in the Genomics
      of Resistance to Immunodeficiency Virus AIDS nonprogression cohort and compared
      them with those of control cohorts. The strongest signals were in MICA, the gene
      encoding major histocompatibility class I polypeptide-related sequence A (P =
      3.31 * 10(-12)), with a particular exonic deletion (P = 1.59 * 10(-8)) in full
      linkage disequilibrium with the reference HCP5 rs2395029 SNP. Haplotype analysis
      also revealed an additive effect between HLA-C, HLA-B, and MICA variants. These
      data suggest a role for MICA in progression and elite control of human
      immunodeficiency virus type 1 infection. 

PMID- 24939906
TI  - Impact of different dosing schedules on the immunogenicity of the human rotavirus
      vaccine in infants in Pakistan: a randomized trial.
AB  - BACKGROUND: Current oral rotavirus vaccines perform suboptimally in resource-poor
      settings. We investigated the effect of an additional dose and later schedule on
      the immunogenicity of monovalent rotavirus vaccine (RV1) in a developing country.
      METHODS: Infants received RV1 at 6 and 10, 10 and 14, or 6, 10, and 14 weeks of
      age. The primary objective was to compare antirotavirus immunoglobulin A (IgA)
      seroconversion at 18 weeks in the 6/10/14 arm to the cumulative seroconversion
      (highest result at 14 or 18 weeks) in the 6/10 arm. RESULTS: Overall, 480 (76.2%)
      of 630 randomized infants completed the trial per protocol. Seroconversion in the
      6/10/14 arm was 36.7% (95% CI, 29.8, 44.2) compared to 36.1% (CI, 29.0, 43.9) in
      the 6/10 arm, (P=1.0); the result from the 10/14 arm was 38.5% (CI, 31.2, 46.3).
      Seroconversion in the 6/10 arm at 14 weeks (post hoc) was lower at 29.7% (CI,
      23.1, 37.3). CONCLUSIONS: In Pakistani infants, the immunogenicity of RV1 did not
      increase significantly with 3 doses at 6, 10, and 14 weeks compared to 2 doses at
      6 and 10 weeks. Additional strategies should be evaluated for improving rotavirus
      vaccine immunogenicity in high burden countries.

PMID- 24939909
TI  - Ambient temperature and the rates of adverse reactions of pertussis vaccines.

PMID- 24939910
TI  - Multiple evidence strands suggest that there may be as few as 19,000 human
      protein-coding genes.
AB  - Determining the full complement of protein-coding genes is a key goal of genome
      annotation. The most powerful approach for confirming protein-coding potential is
      the detection of cellular protein expression through peptide mass spectrometry
      (MS) experiments. Here, we mapped peptides detected in seven large-scale
      proteomics studies to almost 60% of the protein-coding genes in the GENCODE
      annotation of the human genome. We found a strong relationship between detection
      in proteomics experiments and both gene family age and cross-species
      conservation. Most of the genes for which we detected peptides were highly
      conserved. We found peptides for >96% of genes that evolved before bilateria. At
      the opposite end of the scale, we identified almost no peptides for genes that
      have appeared since primates, for genes that did not have any protein-like
      features or for genes with poor cross-species conservation. These results
      motivated us to describe a set of 2001 potential non-coding genes based on
      features such as weak conservation, a lack of protein features, or ambiguous
      annotations from major databases, all of which correlated with low peptide
      detection across the seven experiments. We identified peptides for just 3% of
      these genes. We show that many of these genes behave more like non-coding genes
      than protein-coding genes and suggest that most are unlikely to code for proteins
      under normal circumstances. We believe that their inclusion in the human protein
      coding gene catalogue should be revised as part of the ongoing human genome
      annotation effort. 

PMID- 24939911
TI  - Human stem cell models of dementia.
AB  - Positive predictions were made in the aftermath of the development of induced
      pluripotent stem cell technology for the use of patient-specific iPSCs to model
      neurological diseases, including dementia. Here, we review the current state of
      the field and explore how close we are to the goal of in vitro models that
      capture all aspects of the cell and molecular biology of dementia. 

PMID- 24939912
TI  - Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of
      polycystic kidney disease 1 protein.
AB  - Bardet-Biedl syndrome (BBS) and autosomal dominant polycystic kidney disease
      (ADPKD) are two genetically distinct ciliopathies but share common phenotypes
      such as renal cysts. Seven BBS proteins form a complex called the BBSome which is
      localized at the basal body or ciliary axoneme and regulates the ciliary entry or
      flagellar exit of several signaling molecules. Here, we demonstrate that, unlike
      the seven-span somatostatin receptor 3 or the leptin receptor that interacts with
      all subunits of the BBSome, the ADPKD protein polycystin-1 (PC1) interacts with
      BBS1, BBS4, BBS5 and BBS8, four of the seven components of the BBSome. Only
      depletion or mutation of BBS1, but not depletion of BBS5 and BBS8, or knockout of
      BBS4, impairs ciliary trafficking of PC1 in kidney epithelial cells. Depletion of
      these BBS proteins affects neither the ciliary length nor the plasma membrane
      targeting of PC1. Expression of a pathogenic BBS3/Arl6 mutant (T31R) that locks
      Arl6 in the GDP form leads to stunted cilia and inhibition of PC1 on primary
      cilia. We propose that the 11-span membrane protein PC1 is a BBSome cargo and
      that the components of the BBSome may possess subunit-specific functions.
      Moreover, physical interactions between the BBS and ADPKD proteins may underline
      the overlapping renal phenotypes in these two diseases. 

PMID- 24939915
TI  - Nerve-sparing schwannoma removal from two infrequent origins.
AB  - Schwannomas of nerve sheath origin (Schwann cell) are the most common neurogenic
      thoracic tumors and they usually originate from an intercostal nerve, especially
      in the paravertebral region. Tumors that originate from other nerves such as the
      phrenic nerve, vagus, or sympathetic nerves are uncommon. We report two cases of
      schwannomas in rare locations. A 62-year-old woman had a giant schwannoma arising
      from the right phrenic nerve, and a 57-year-old woman had one from the left
      sympathetic nerve. Both tumors were completely removed with preservation of the
      nerves. 

PMID- 24939913
TI  - 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic
      epilepsy.
AB  - Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy.
      Its molecular basis is largely unknown and a complex genetic etiology is assumed
      in the majority of affected individuals. The present study tested whether six
      large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11
      and 22q11.2 previously associated with neurodevelopmental disorders also increase
      risk of RE. Our association analyses revealed a significant excess of the 600 kb
      genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated
      patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the
      prevalence in 65,046 European population controls (5/393 cases versus 32/65,046
      controls; Fisher's exact test P = 2.83 * 10(-6), odds ratio = 26.2, 95%
      confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not
      detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n
      = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective
      enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies
      (Fisher's exact test P = 2.1 * 10(-4)). In a subsequent screen among children
      carrying the 16p11.2 600 kb rearrangement we identified three patients with RE
      spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers
      of the reciprocal deletion. Our results suggest that the 16p11.2 duplication
      represents a significant genetic risk factor for typical and atypical RE.

PMID- 24939914
TI  - Multiple ruptures of left sinus of Valsalva aneurysm into main pulmonary artery.
AB  - Sinus of Valsalva aneurysm is a rare congenital glitch. We report an extremely
      rare case of left sinus of Valsalva aneurysm compressing and rupturing into the
      main pulmonary artery with 2 communications. The 34-year-old man also had severe
      aortic regurgitation and severe tricuspid regurgitation. He underwent successful
      polytetrafluoroethylene patch repair and aortic valve replacement. The rarity of
      this case highlights the need for a precise preoperative diagnosis, the roles of
      transthoracic echocardiography, transesophageal echocardiography, and 3
      dimensional echocardiography, and the importance of prompt surgical management. 

PMID- 24939916
TI  - Impact of a postdischarge smoking cessation intervention for smokers admitted to
      an inpatient psychiatric facility: a randomized controlled trial.
AB  - INTRODUCTION: Persons with a mental disorder smoke at higher rates and suffer
      disproportionate tobacco-related burden compared with the general population. The
      aim of this study was to determine if a smoking cessation intervention initiated
      during a psychiatric hospitalization and continued postdischarge was effective in
      reducing smoking behaviors among persons with a mental disorder. METHODS: A
      randomized controlled trial was conducted at an Australian inpatient psychiatric
      facility. Participants were 205 patient smokers allocated to a treatment as usual
      control (n = 101) or a smoking cessation intervention (n = 104) incorporating
      psychosocial and pharmacological support for 4 months postdischarge. Follow-up
      assessments were conducted at 1 week, 2, 4, and 6 months postdischarge and
      included abstinence from cigarettes, quit attempts, daily cigarette consumption,
      and nicotine dependence. RESULTS: Rates of continuous and 7-day point prevalence
      abstinence did not differ between treatment conditions at the 6-month follow-up;
      however, point prevalence abstinence was significantly higher for intervention
      (11.5%) compared with control (2%) participants at 4 months (OR = 6.46, p = .01).
      Participants in the intervention condition reported significantly more quit
      attempts (F[1, 202.5] = 15.23, p = .0001), lower daily cigarette consumption
      (F[4, 586] = 6.5, p < .001), and lower levels of nicotine dependence (F[3, 406] =
      8.5, p < .0001) compared with controls at all follow-up assessments. CONCLUSIONS:
      Postdischarge cessation support was effective in encouraging quit attempts and
      reducing cigarette consumption up to 6 months postdischarge. Additional support
      strategies are required to facilitate longer-term cessation benefits for smokers
      with a mental disorder.

PMID- 24939920
TI  - Board Walk - July 2014.

PMID- 24939918
TI  - Comment on: Application of endovascular stent placement as a remedy for
      spontaneous isolated superior mesenteric artery dissection.

PMID- 24939919
TI  - Surviving an abdominal aortic aneurysm type II endoleak rupture without surgical
      intervention.
AB  - We describe a patient who survived a ruptured abdominal aortic aneurysm without
      any surgical intervention. The patient had previously had endovascular repair of
      the aneurysm and surveillance of a stable persistent type II endoleak. This case
      highlights the difficulties surrounding type II endoleak, its natural history,
      and the ongoing controversies of its management. 

PMID- 24939922
TI  - Isoflavones hold limited promise for the treatment of menopausal vasomotor
      symptoms.

PMID- 24939917
TI  - Practical application of bedside diagnostics in determining limb viability.
AB  - INTRODUCTION: This study aimed to determine the practical application of vascular
      lab studies in determining limb salvage outcomes in injured patients with
      concerning clinical examinations. METHODS: A retrospective review of the trauma
      registry at a level I center was conducted from January 2009 to June 2013. All
      patients >16 years of age who sustained a lower limb arterial injury had a
      concerning clinical exam (mottled skin, decreased skin warmth, diminished pulses)
      and had vascular lab studies to determine management were included. Data-points
      included demographics, type and location of injury, procedure type, vascular lab
      study results, and limb outcome. RESULTS: Over a five-year period, 11 trauma
      patients met inclusion criteria. Five of these patients had concerning clinical
      exams after revascularization, and six observed patients had a concerning
      clinical examination during the course of their hospitalization. All 11 patients
      had vascular lab studies that were within normal limits. As a result of normal
      vascular lab studies, none of these patients underwent further imaging or
      intervention. None of these patients underwent amputation. CONCLUSION: Vascular
      lab studies may be utilized to determine the need for intervention and/or lower
      limb bypass sufficiency in patients with questionable clinical examinations post
      injury.

PMID- 24939921
TI  - Characterization of acyl chain position in unsaturated phosphatidylcholines using
      differential mobility-mass spectrometry.
AB  - Glycerophospholipids (GPs) that differ in the relative position of the two fatty
      acyl chains on the glycerol backbone (i.e., sn-positional isomers) can have
      distinct physicochemical properties. The unambiguous assignment of acyl chain
      position to an individual GP represents a significant analytical challenge. Here
      we describe a workflow where phosphatidylcholines (PCs) are subjected to ESI for
      characterization by a combination of differential mobility spectrometry and MS
      (DMS-MS). When infused as a mixture, ions formed from silver adduction of each
      phospholipid isomer {e.g., [PC (16:0/18:1) + Ag](+) and [PC (18:1/16:0) + Ag](+)}
      are transmitted through the DMS device at discrete compensation voltages. Varying
      their relative amounts allows facile and unambiguous assignment of the sn
      positions of the fatty acyl chains for each isomer. Integration of the well
      resolved ion populations provides a rapid method (< 3 min) for relative
      quantification of these lipid isomers. The DMS-MS results show excellent
      agreement with established, but time-consuming, enzymatic approaches and also
      provide superior accuracy to methods that rely on MS alone. The advantages of
      this DMS-MS method in identification and quantification of GP isomer populations
      is demonstrated by direct analysis of complex biological extracts without any
      prior fractionation. 

PMID- 24939923
TI  - A targeted approach reduces prostate cancer-specific (PSA) screening harms while
      preserving benefits.

PMID- 24939924
TI  - A viscous lidocaine mouthwash is no better than placebo for improving oral intake
      in children with painful mouth ulcers.

PMID- 24939926
TI  - It's all about the six-pack: Boys' bodies in contemporary Western culture.
AB  - This is an article about boys and their construction of masculinities. It draws
      on 5 years of qualitative research data from the same group of boys from early
      childhood through to 10 years of age in an attempt to articulate the way in which
      boys come to view their bodies, and other male bodies, in contemporary Western
      culture. The research is based on focus groups and is a part of a longitudinal
      study with the same cohort of boys, at a school in Adelaide, Australia. The data
      were analysed using inductive thematic analysis to identify key emergent themes.
      The results indicate that there is an emerging trend among boys from early
      childhood through to middle primary school surrounding the acknowledgement of
      male body aesthetics as a signifier of being male. The use of terminology such as
      'six-pack' is now commonplace among all of the groups. The consistency around
      muscularity as a signifier of being a man was very high among the boys of all
      ages. It is clear that greater emphasis needs to be placed on younger males' and
      boys' awareness of the meaning of the male body in contemporary Western society. 

PMID- 24939925
TI  - Quantitative genomics of voluntary exercise in mice: transcriptional analysis and
      mapping of expression QTL in muscle.
AB  - Motivation and ability both underlie voluntary exercise, each with a potentially
      unique genetic architecture. Muscle structure and function are one of many
      morphological and physiological systems acting to simultaneously determine
      exercise ability. We generated a large (n = 815) advanced intercross line of mice
      (G4) derived from a line selectively bred for increased wheel running (high
      runner) and the C57BL/6J inbred strain. We previously mapped quantitative trait
      loci (QTL) contributing to voluntary exercise, body composition, and changes in
      body composition as a result of exercise. Using brain tissue in a subset of the
      G4 (n = 244), we have also previously reported expression QTL (eQTL) colocalizing
      with the QTL for the higher-level phenotypes. Here, we examined the
      transcriptional landscape of hind limb muscle tissue via global mRNA expression
      profiles. Correlations revealed an ~1,168% increase in significant relationships
      between muscle transcript expression levels and the same exercise and body
      composition phenotypes examined previously in the brain. The exercise trait most
      often significantly correlated with gene expression in the brain was running
      duration while in the muscle it was maximum running speed. This difference may
      indicate that time spent engaging in exercise behavior may be more influenced by
      central (neurobiological) mechanisms, while intensity of exercise may be largely
      controlled by peripheral mechanisms. Additionally, we used subsets of cis-acting
      eQTL, colocalizing with QTL, to identify candidate genes based on both positional
      and functional evidence. We discuss three plausible candidate genes (Insig2,
      Prcp, Sparc) and their potential regulatory role. 

PMID- 24939927
TI  - Outcomes with coronary artery bypass graft surgery versus percutaneous coronary
      intervention for patients with diabetes mellitus: can newer generation drug
      eluting stents bridge the gap?
AB  - BACKGROUND: Coronary artery bypass graft surgery (CABG) compared with
      percutaneous coronary intervention (PCI) reduces mortality in patients with
      diabetes mellitus. However, prior trials compared CABG with balloon angioplasty
      or older generation stents, and it is not known if the gap between CABG and PCI
      can be reduced by newer generation drug-eluting stents. METHODS AND RESULTS:
      PUBMED/EMBASE/CENTRAL search for randomized trials comparing mode of
      revascularization in patients with diabetes mellitus. Primary outcome was all
      cause mortality. Secondary outcomes were myocardial infarction, repeat
      revascularization, and stroke. Mixed treatment comparison analyses were performed
      using a random-effects Poisson regression model. Sixty-eight randomized trials
      that enrolled 24 015 diabetic patients with a total of 71 595 patient-years of
      follow-up satisfied our inclusion criteria. When compared with CABG (reference
      rate ratio [RR]=1.0), PCI with paclitaxel-eluting stent (RR=1.57 [1.15-2.19]) or
      sirolimus-eluting stent (RR=1.43 [1.06-1.97]) was associated with an increase in
      mortality. However, PCI with cobalt-chromium everolimus-eluting stent (RR=1.11
      [0.67-1.84]) was not associated with a statistically significant increase in
      mortality. When compared with CABG, there was excess repeat revascularization
      with PCI, which progressively declined from plain old balloon angioplasty (341%
      increase) to bare metal stent (218% increase) to paclitaxel-eluting stent (81%
      increase) and to sirolimus-eluting stent (47% increase). However, for PCI with
      cobalt-chromium everolimus-eluting stent (RR=1.31 [0.74-2.29]), the excess repeat
      revascularization was not statistically significant although the point estimate
      favored CABG. CABG was associated with numerically higher stroke. CONCLUSIONS: In
      patients with diabetes mellitus, evidence from indirect comparison shows similar
      mortality between CABG and PCI using cobalt-chromium everolimus-eluting stent.
      CABG was associated with numerically excess stroke and PCI with cobalt-chromium
      everolimus-eluting stent with numerically increased repeat revascularization.
      This hypothesis needs to be tested in future trials.

PMID- 24939928
TI  - Incidence, predictors, and implications of reinfarction after primary
      percutaneous coronary intervention in ST-segment-elevation myocardial infarction:
      the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial
      Infarction Trial.
AB  - BACKGROUND: Reinfarction after primary percutaneous coronary intervention in
      patients with ST-segment-elevation myocardial infarction has negative
      consequences. Little is known about reinfarction after drug-eluting stents and
      bivalirudin anticoagulation. We, therefore, sought to determine the incidence,
      predictors, and implications of reinfarction after primary percutaneous coronary
      intervention in the contemporary era. METHODS AND RESULTS: Outcomes were assessed
      in 3202 patients undergoing stent implantation for ST-segment-elevation
      myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and
      Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent
      predictors of reinfarction and mortality were identified by Cox proportional
      hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days,
      4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible
      for 76.3% of reinfarctions occurring within 30 days and 52.0% of all
      reinfarctions within 3 years. Independent predictors of reinfarction were current
      smoking, Killip class >=2, baseline thrombocytosis, multivessel disease, symptom
      onset-to-balloon time, and total stent length. Randomization to bivalirudin
      versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting
      versus bare metal stents were not significant predictors of reinfarction.
      Reinfarction was a powerful independent predictor of subsequent cardiac mortality
      (hazard ratio [95% confidence interval]=7.65 [4.47-13.09]; P<0.0001) and all
      cause mortality (hazard ratio [95% confidence interval]=2.88 [1.74-4.78];
      P<0.0001). CONCLUSIONS: Despite advances in pharmacotherapy and stents,
      reinfarction after primary percutaneous coronary intervention is not infrequent,
      in the contemporary era is most often attributable to stent thrombosis, and is
      strongly associated with subsequent cardiac and all-cause mortality. Further
      enhancements in drugs and devices to prevent reinfarction are needed to improve
      outcomes in high-risk patients with ST-segment-elevation myocardial infarction.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00433966.

PMID- 24939929
TI  - Median arcuate ligament syndrome: Use of fractional flow reserve in documentation
      of chronic mesenteric ischemia.
AB  - Median arcuate ligament syndrome (MALS) is a rare clinical entity. This condition
      typically affects women between the ages of 20 and 40 years and causes symptoms
      of abdominal pain, primarily post-prandial, as well as nausea, vomiting and
      weight loss. MALS is considered a diagnosis of exclusion. Typically, mesenteric
      arterial duplex ultrasonography, computed tomography (CT), and magnetic resonance
      (MR) are highly suggestive, and conventional contrast angiography confirmatory.
      We explore the role of fractional flow reserve and intravascular ultrasound in
      the evaluation of MALS. In order to illustrate the utility of these tools, we
      present the case of a 47-year-old symptomatic woman who underwent angiography,
      complemented by assessment of fractional flow reserve and intravascular
      ultrasound. These data convincingly demonstrated the dynamic nature of the
      obstructive characteristic of MALS.

PMID- 24939930
TI  - Association of elevated fasting glucose with lower patency and increased major
      adverse limb events among patients with diabetes undergoing infrapopliteal
      balloon angioplasty.
AB  - Diabetes mellitus (DM) is a significant risk factor for loss of patency after
      endovascular intervention, but the contribution of glycemic control to
      infrapopliteal artery patency among patients with DM is unknown. All percutaneous
      infrapopliteal interventions among patients with DM from 2006 to 2013 were
      reviewed and pre-procedure fasting blood glucose (FBG) was recorded. The primary
      endpoint was primary patency at 1 year as determined by duplex ultrasound. A
      total of 309 infrapopliteal lesions in 149 patients with DM were treated with
      balloon angioplasty during the study period. The median FBG was 144 mg/dL. At 1
      year, the rate of primary patency was 16% for patients with FBG above the median,
      compared to 46% for patients with FBG below the median (hazard ratio (HR) 1.82
      for FBG >=144, p=0.005). Amputation rates at 1 year trended higher among patients
      with high versus low FBG (24% vs 15%, p=0.1). One year major adverse limb event
      rates were also higher for patients with high versus low FBG (35% vs 23%,
      p=0.05). Although patients with high FBG were more likely to have insulin
      requiring DM (73% vs 50%, p=0.003) the association of high FBG with loss of
      primary patency remained significant even after adjusting for insulin use as well
      as other lesion-specific characteristics (adjusted HR 1.8, 95% CI 1.2-2.8). In
      conclusion, high fasting blood glucose at the time of infrapopliteal balloon
      angioplasty is associated with significantly decreased primary patency and may
      also be a risk factor for major adverse limb events among patients with a
      threatened limb.

PMID- 24939931
TI  - Relationship Between Standardized Glycemic Protocols and Healthcare Cost.
AB  - Rising healthcare costs and the management of diabetes are financially straining
      to healthcare organizations. The study purpose was to examine whether a direct
      relationship existed between the cost of hospitalization, length of stay, excess
      admission days, and discharge blood glucose (DC-BG) levels and utilizing a
      standardized glycemic protocol. A retrospective cohort analysis was conducted of
      adult diabetes mellitus type 2 (DM-2) patients' pre-diabetic protocol (January 1,
      2011-December 31, 2011) and post-diabetic protocol (August 1, 2012-October 31,
      2012). The sample included DM-2 inpatients aged >= 18 years admitted without
      complications and/or with abnormal fasting blood glucose. Pre-protocol sample
      comprised n = 346 subjects and post-protocol sample comprised n = 149 subjects.
      Patients who received the diabetic protocol in 2012 experienced a decrease in the
      DC-BG (p < .05) and decrease in excess admission days (p < .05). Evidence
      supports that utilizing a standardized glycemic protocol improves glycemic
      control and reduces healthcare cost.

PMID- 24939935
TI  - How an mRNA capping enzyme reads distinct RNA polymerase II and Spt5 CTD
      phosphorylation codes.
AB  - Interactions between RNA guanylyltransferase (GTase) and the C-terminal domain
      (CTD) repeats of RNA polymerase II (Pol2) and elongation factor Spt5 are thought
      to orchestrate cotranscriptional capping of nascent mRNAs. The crystal structure
      of a fission yeast GTase*Pol2 CTD complex reveals a unique docking site on the
      nucleotidyl transferase domain for an 8-amino-acid Pol2 CTD segment,
      S5PPSYSPTS5P, bracketed by two Ser5-PO4 marks. Analysis of GTase mutations that
      disrupt the Pol2 CTD interface shows that at least one of the two Ser5-PO4
      binding sites is required for cell viability and that each site is important for
      cell growth at 37 degrees C. Fission yeast GTase binds the Spt5 CTD at a separate
      docking site in the OB-fold domain that captures the Trp4 residue of the Spt5
      nonapeptide repeat T(1)PAW(4)NSGSK. A disruptive mutation in the Spt5 CTD-binding
      site of GTase is synthetically lethal with mutations in the Pol2 CTD-binding
      site, signifying that the Spt5 and Pol2 CTDs cooperate to recruit capping enzyme
      in vivo. CTD phosphorylation has opposite effects on the interaction of GTase
      with Pol2 (Ser5-PO4 is required for binding) versus Spt5 (Thr1-PO4 inhibits
      binding). We propose that the state of Thr1 phosphorylation comprises a binary
      "Spt5 CTD code" that is read by capping enzyme independent of and parallel to its
      response to the state of the Pol2 CTD. 

PMID- 24939934
TI  - PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic
      regulator.
AB  - dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well
      known for its roles in immune response. Upon binding to viral dsRNA, PKR
      undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates
      translation and multiple signaling pathways in infected cells. Here, we found
      that PKR is activated in uninfected cells, specifically during mitosis, by
      binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu
      containing RNAs are segregated in the cytosol and nucleus of interphase cells,
      respectively, they interact during mitosis when nuclear structure is disrupted.
      Once phosphorylated, PKR suppresses global translation by phosphorylating the
      alpha subunit of eukaryotic initiation factor 2 (eIF2alpha). In addition, pPKR
      acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels
      of multiple mitotic factors such as cyclins A and B and Polo-like kinase 1 and
      phosphorylation of histone H3. Disruption of PKR activation via RNAi or
      expression of a transdominant-negative mutant leads to misregulation of the
      mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our
      study unveils a novel function of PKR and endogenous dsRNAs as signaling
      molecules during the mitosis of uninfected cells.

PMID- 24939932
TI  - Unlocking epigenetic codes in neurogenesis.
AB  - During embryonic and adult neurogenesis, neuronal stem cells follow a highly
      conserved path of differentiation to give rise to functional neurons at various
      developmental stages. Epigenetic regulation--including DNA modifications, histone
      modifications, and noncoding regulatory RNAs, such as microRNA (miRNA) and long
      noncoding RNA (lncRNA)--plays a pivotal role in embryonic and adult neurogenesis.
      Here we review the latest in our understanding of the epigenetic regulation in
      neurogenesis, with a particular focus on newly identified cytosine modifications
      and their dynamics, along with our perspective for future studies.

PMID- 24939933
TI  - Tension-dependent removal of pericentromeric shugoshin is an indicator of sister
      chromosome biorientation.
AB  - During mitosis and meiosis, sister chromatid cohesion resists the pulling forces
      of microtubules, enabling the generation of tension at kinetochores upon
      chromosome biorientation. How tension is read to signal the bioriented state
      remains unclear. Shugoshins form a pericentromeric platform that integrates
      multiple functions to ensure proper chromosome biorientation. Here we show that
      budding yeast shugoshin Sgo1 dissociates from the pericentromere reversibly in
      response to tension. The antagonistic activities of the kinetochore-associated
      Bub1 kinase and the Sgo1-bound phosphatase protein phosphatase 2A (PP2A)-Rts1
      underlie a tension-dependent circuitry that enables Sgo1 removal upon sister
      kinetochore biorientation. Sgo1 dissociation from the pericentromere triggers
      dissociation of condensin and Aurora B from the centromere, thereby stabilizing
      the bioriented state. Conversely, forcing sister kinetochores to be under tension
      during meiosis I leads to premature Sgo1 removal and precocious loss of
      pericentromeric cohesion. Overall, we show that the pivotal role of shugoshin is
      to build a platform at the pericentromere that attracts activities that respond
      to the absence of tension between sister kinetochores. Disassembly of this
      platform in response to intersister kinetochore tension signals the bioriented
      state. Therefore, tension sensing by shugoshin is a central mechanism by which
      the bioriented state is read. 

PMID- 24939939
TI  - Association between operator procedure volume and patient outcomes in
      percutaneous coronary intervention: a systematic review and meta-analysis.
AB  - BACKGROUND: The growth of centers capable of performing percutaneous coronary
      intervention (PCI) has outpaced population growth despite declining incidence of
      myocardial infarction and prevalence of coronary artery disease, potentially
      increasing the proportion of operators falling below minimal yearly volume
      standards set by professional societies. METHODS AND RESULTS: Electronic
      literature search of MEDLINE and the Cochrane Library for English-language
      articles published between 1977 and November 2012 was performed. Title and
      abstract review followed by full-text and references review were performed by 2
      authors independently to identify studies examining the association between
      operator volume and outcomes in PCI. Using a standardized form, 2 authors
      abstracted information on study design, methods, outcomes, statistical methods,
      and conclusions. Studies were categorized according to methodological quality and
      outcomes. Meta-analyses were performed by outcome using a random-effects model.
      Of the 23 studies included in the analysis, 14 (61%) evaluated mortality, 7 (30%)
      evaluated major adverse cardiac events, and 2 (9%) evaluated angiographic
      success. In total, the studies evaluated 15 907 operators performing 205 214 PCIs
      on 1 109 103 patients at 2456 centers with a mean follow-up of 2.8 years. Eleven
      (48%) were considered higher quality. Studies with higher methodological quality
      and large sample sizes more often showed a relationship between operator volume
      and outcomes in PCI. Higher volume was associated with improved major adverse
      cardiac events at every threshold, regardless of the threshold evaluated.
      CONCLUSIONS: Mortality and major adverse cardiac events increase as operator
      volumes decrease in PCI. Among studies showing a relationship, high-volume
      operators were defined variably, with annual PCIs ranging from >11 to >270, with
      no clear evidence of a threshold effect within the ranges studied.

PMID- 24939936
TI  - Pax5 loss imposes a reversible differentiation block in B-progenitor acute
      lymphoblastic leukemia.
AB  - Loss-of-function mutations in hematopoietic transcription factors including PAX5
      occur in most cases of B-progenitor acute lymphoblastic leukemia (B-ALL), a
      disease characterized by the accumulation of undifferentiated lymphoblasts.
      Although PAX5 mutation is a critical driver of B-ALL development in mice and
      humans, it remains unclear how its loss contributes to leukemogenesis and whether
      ongoing PAX5 deficiency is required for B-ALL maintenance. Here we used
      transgenic RNAi to reversibly suppress endogenous Pax5 expression in the
      hematopoietic compartment of mice, which cooperates with activated signal
      transducer and activator of transcription 5 (STAT5) to induce B-ALL. In this
      model, restoring endogenous Pax5 expression in established B-ALL triggers
      immunophenotypic maturation and durable disease remission by engaging a
      transcriptional program reminiscent of normal B-cell differentiation. Notably,
      even brief Pax5 restoration in B-ALL cells causes rapid cell cycle exit and
      disables their leukemia-initiating capacity. These and similar findings in human
      B-ALL cell lines establish that Pax5 hypomorphism promotes B-ALL self-renewal by
      impairing a differentiation program that can be re-engaged despite the presence
      of additional oncogenic lesions. Our results establish a causal relationship
      between the hallmark genetic and phenotypic features of B-ALL and suggest that
      engaging the latent differentiation potential of B-ALL cells may provide new
      therapeutic entry points. 

PMID- 24939942
TI  - It's just a coronary milking-like effect ... or maybe not: posterolateral artery
      compression caused by a ventricle pseudoaneurysm.

PMID- 24939943
TI  - Chronic active Epstein-Barr virus infection complicated with multiple artery
      aneurysms.

PMID- 24939940
TI  - Hospital variation in survival after pediatric in-hospital cardiac arrest.
AB  - BACKGROUND: Although survival after in-hospital cardiac arrest is likely to vary
      among hospitals caring for children,validated methods to risk-standardize
      pediatric survival rates across sites do not currently exist. METHODS AND
      RESULTS: From 2006 to 2010, within the American Heart Association's Get With the
      Guidelines-Resuscitation registry for in-hospital cardiac arrest, we identified
      1551 cardiac arrests in children (<18 years). Using multivariable hierarchical
      logistic regression, we developed and validated a model to predict survival to
      hospital discharge and calculated risk-standardized rates of cardiac arrest
      survival for hospitals with a minimum of 10 pediatric cardiac arrest cases. A
      total of 13 patient-level predictors were identified: age, sex, cardiac arrest
      rhythm, location of arrest, mechanical ventilation, acute nonstroke neurological
      event, major trauma, hypotension, metabolic or electrolyte abnormalities, renal
      insufficiency, sepsis, illness category, and need for intravenous vasoactive
      agents prior to the arrest. The model had good discrimination (C-statistic of
      0.71), confirmed by bootstrap validation (validation C-statistic of 0.69). Among
      30 hospitals with >=10 cardiac arrests, unadjusted hospital survival rates varied
      considerably (median, 37%; interquartile range, 24-42%; range, 0-61%). After risk
      standardization, the range of hospital survival rates narrowed (median, 37%;
      interquartile range, 33-38%; range, 29-48%), but variation in survival persisted.
      CONCLUSIONS: Using a national registry, we developed and validated a model to
      predict survival after in-hospital cardiac arrest in children. After risk
      standardization, significant variation in survival rates across hospitals
      remained. Leveraging these models, future studies can identify best practices at
      high-performing hospitals to improve survival outcomes for pediatric cardiac
      arrest. (

PMID- 24939941
TI  - Prognostic implications of non-culprit plaques in acute coronary syndrome: non
      invasive assessment with coronary CT angiography.
AB  - AIMS: Non-culprit plaques are responsible for a substantial number of future
      events in patients with acute coronary syndrome (ACS). In this study, we
      evaluated the prognostic implications of non-culprit plaques seen on coronary
      computed tomography angiography (CTA) in patients with ACS. METHODS AND RESULTS:
      Coronary CTA was performed in 169 patients (mean 59 +/- 11 years, 129 males)
      admitted with ACS. Data sets were assessed for the presence of obstructive non
      culprit plaques (>50% luminal narrowing), segment involvement score, and
      quantitative measures of plaque burden, after censoring initial culprit plaques.
      Follow-up was performed for the occurrence of major adverse cardiovascular events
      (MACEs) unrelated to the initial culprit plaque; cardiac death, second ACS, or
      coronary revascularization after 90 days. After a median follow-up of 4.8 (IQR
      2.6-6.6) years, MACE occurred in 36 (24%) patients: 6 cardiac deaths, 16 second
      ACS, and 14 coronary revascularizations. Dyslipidaemia (hazard ratio [HR] 3.1
      [95% confidence interval 1.5-6.6]) and diabetes mellitus (HR 4.8 [2.3-10.3]) were
      univariable clinical predictors of MACE. Patients with remaining obstructive non
      culprit plaques (HR 3.66 [1.52-8.80]) and higher plaque burden index (HR 1.22
      [1.01-1.48]) had a more risk of MACE. In multivariate analysis, with diabetes,
      dyslipidaemia, and plaque burden index, obstructive non-culprit plaques (HR 3.76
      [1.28-11.09]) remained an independent predictor of MACE. CONCLUSION: Almost a
      quarter of the study population experienced a new event arising from a non
      culprit plaque during a follow-up of almost 5 years. ACS patients with remaining
      obstructive non-culprit plaques or high plaque burden have an increased risk of
      future MACE.

PMID- 24939937
TI  - Functional and molecular features of the Id4+ germline stem cell population in
      mouse testes.
AB  - The maintenance of cycling cell lineages relies on undifferentiated
      subpopulations consisting of stem and progenitor pools. Features that delineate
      these cell types are undefined for many lineages, including spermatogenesis,
      which is supported by an undifferentiated spermatogonial population. Here, we
      generated a transgenic mouse line in which spermatogonial stem cells are marked
      by expression of an inhibitor of differentiation 4 (Id4)-green fluorescent
      protein (Gfp) transgene. We found that Id4-Gfp(+) cells exist primarily as a
      subset of the type A(single) pool, and their frequency is greatest in neonatal
      development and then decreases in proportion during establishment of the
      spermatogenic lineage, eventually comprising ~ 2% of the undifferentiated
      spermatogonial population in adulthood. RNA sequencing analysis revealed that
      expression of 11 and 25 genes is unique for the Id4-Gfp(+)/stem cell and Id4-Gfp(
      )/progenitor fractions, respectively. Collectively, these findings provide the
      first definitive evidence that stem cells exist as a rare subset of the A(single)
      pool and reveal transcriptome features distinguishing stem cell and progenitor
      states within the mammalian male germline.

PMID- 24939944
TI  - Association of tricuspid regurgitation with clinical and echocardiographic
      outcomes after percutaneous mitral valve repair with the MitraClip System: 30-day
      and 12-month follow-up from the GRASP Registry.
AB  - AIM: The aim of this study was to evaluate the association of baseline tricuspid
      regurgitation (TR) on the outcomes after percutaneous mitral valve repair (PMVR)
      with the MitraClip system. METHODS AND RESULTS: Data from 146 consecutive
      patients with functional mitral regurgitation (MR) were obtained. Two different
      groups, dichotomized according to the degree of pre-procedural TR
      (moderate/severe, n = 47 and none/mild, n = 99), had their clinical and
      echocardiographic outcomes through 12-month compared. At 30-day, the primary
      safety endpoint was significantly higher in moderate/severe TR compared with
      none/mild TR (10.6 vs. 2.0%, P = 0.035). Marked reduction in MR grades observed
      post-procedure were maintained through 12 months. Although NYHA functional class
      significantly improved in both groups compared with baseline, it was impaired in
      moderate/severe TR compared with the none/mild TR group (NYHA > II at 30 day:
      33.3 vs. 9.2%, P < 0.001; at 1 year: 38.5 vs. 12.3%, respectively, P = 0.006).
      Left ventricle reverse remodelling and ejection fraction improvement were
      revealed in both groups. The primary efficacy endpoint at 12-month determined by
      freedom from death, surgery for mitral valve dysfunction, or grade >= 3+ MR was
      comparable between groups, but combined death and re-hospitalization for heart
      failure rates were higher in the moderate/severe TR group. Multivariable Cox
      regression analysis demonstrated that baseline moderate/severe TR and chronic
      kidney disease were independent predictors of this combined endpoint.
      CONCLUSIONS: Although PMVR with MitraClip led to improvement in MR, TR, and NYHA
      functional class in patients with baseline moderate/severe TR, the primary safety
      endpoint at 30-day was impaired, while moderate/severe TR independently predicted
      death and re-hospitalization for heart failure at 12-month.

PMID- 24939938
TI  - Long noncoding RNAs are spatially correlated with transcription factors and
      regulate lung development.
AB  - Long noncoding RNAs (lncRNAs) are thought to play important roles in regulating
      gene transcription, but few have well-defined expression patterns or known
      biological functions during mammalian development. Using a conservative pipeline
      to identify lncRNAs that have important biological functions, we identified 363
      lncRNAs in the lung and foregut endoderm. Importantly, we show that these lncRNAs
      are spatially correlated with transcription factors across the genome. In-depth
      expression analyses of lncRNAs with genomic loci adjacent to the critical
      transcription factors Nkx2.1, Gata6, Foxa2 (forkhead box a2), and Foxf1 mimic the
      expression patterns of their protein-coding neighbor. Loss-of-function analysis
      demonstrates that two lncRNAs, LL18/NANCI (Nkx2.1-associated noncoding intergenic
      RNA) and LL34, play distinct roles in endoderm development by controlling
      expression of critical developmental transcription factors and pathways,
      including retinoic acid signaling. In particular, we show that LL18/NANCI acts
      upstream of Nkx2.1 and downstream from Wnt signaling to regulate lung endoderm
      gene expression. These studies reveal that lncRNAs play an important role in
      foregut and lung endoderm development by regulating multiple aspects of gene
      transcription, often through regulation of transcription factor expression. 

PMID- 24939947
TI  - Integrated CT ad MR imaging in alcohol-related isolated left ventricular fatty
      infiltration.

PMID- 24939946
TI  - Prosthetic valve dysfunction in repaired tetralogy of Fallot: assessment by FDG
      PET and 256-slice 4D-CT.

PMID- 24939948
TI  - Unusual Doppler finding in fatal right ventricular outflow obstruction caused by
      lymphoma.

PMID- 24939945
TI  - Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid
      scintigraphy in systemic amyloidosis.
AB  - AIMS: Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid
      ((99m)Tc-DPD) is a sensitive method for imaging cardiac transthyretin (ATTR)
      amyloid. We report utility and limitations of (99m)Tc-DPD scintigraphy in 321
      patients with suspected cardiac amyloidosis. METHODS AND RESULTS: The cohort
      included wild-type ATTR (ATTRwt) amyloidosis in 94 (29%), ATTR-Val122Ile
      amyloidosis in 38 (12%), hereditary ATTR (ATTRmt) amyloidosis in 46 (14%),
      primary light-chain (AL) amyloidosis in 44 (14%), secondary (AA) amyloidosis in
      three (1%), other hereditary amyloidosis types in nine (3%), undetermined types
      in two (0.5%), and 85 (26.5%) patients in whom systemic amyloidosis was
      ultimately excluded. All 158 patients with ATTR amyloidosis with clinical cardiac
      involvement had cardiac (99m)Tc-DPD uptake, with median Grade 2 intensity.
      Thirteen further ATTR amyloidosis patients without clinical evidence of cardiac
      involvement also demonstrated (99m)Tc-DPD cardiac uptake. Eighteen of 35 (51%) AL
      patients with cardiac involvement had (99m)Tc-DPD cardiac uptake (median Grade 1
      intensity). SPECT imaging indicates that the apparent reciprocal reduction in
      bone uptake is due to masking of bone uptake by extensive soft-tissue uptake in
      ATTR amyloidosis, especially ATTRwt, and ATTR-Val122Ile types. CONCLUSION:
      (99m)Tc-DPD scintigraphy is a highly sensitive technique for imaging cardiac ATTR
      amyloidosis and is an important investigation in the diagnostic pathway of
      patients with cardiac amyloidosis. It is not specific for ATTR in isolation but
      must be interpreted in a broad clinical context to avoid dangerous diagnostic
      errors. Diffuse skeletal muscle uptake identifies muscle as a hitherto
      unrecognized site that merits investigation as a target organ in ATTR
      amyloidosis.

PMID- 24939950
TI  - Importance of live three-dimensional transoesophageal echocardiography in the
      early recognition of an asymptomatic but extensive annular and left ventricular
      outflow track rupture following transcatheter aortic valve replacement.

PMID- 24939949
TI  - The diagnostic performance of imaging methods in ARVC using the 2010 Task Force
      criteria.
AB  - AIMS: This study evaluates the agreement between echocardiographic and cardiac
      magnetic resonance (CMR) imaging data, and the impact a discrepancy between the
      two may have on the clinical diagnosis of arrhythmogenic right ventricular
      cardiomyopathy (ARVC). METHODS AND RESULTS: From the Nordic ARVC Registry, 102
      patients with definite ARVC who had undergone both echocardiography and CMR were
      included (median age 42 +/- 16 years, 36% female, 78% probands). Patients were
      divided into two groups according to CMR-positive or -negative criteria, and the
      echocardiographic data were compared between the two. There were 72 CMR-positive
      patients. They had significantly larger RV dimensions and lower fractional area
      change on echocardiography compared with CMR-negative patients; parasternal long
      axis right ventricular outflow tract (RVOT) 37 +/- 7 vs. 32 +/- 5 mm, parasternal
      short-axis RVOT 38 +/- 7 vs. 32 +/- 6 mm, fractional area shortening 31 +/- 9 vs.
      39 +/- 9% (P < 0.003 for all). Only 36 (50%) of the CMR-positive patients
      fulfilled ARVC criteria by echocardiography, hence the diagnostic performance was
      low; sensitivity 50% and specificity 70%, positive predictive value 80% and
      negative predictive value 37%. Individuals with regional wall abnormalities on
      CMR were more likely to have ventricular arrhythmias (77 vs. 57%, P = 0.047).
      CONCLUSION: A significant proportion of patients with imaging-positive ARVC by
      CMR did not fulfil echocardiographic ARVC 2010 criteria. These findings confirm
      that echocardiographic evaluation of subtle structural changes in the right
      ventricle may be unreliable, and the diagnostic performance of CMR compared with
      echocardiography should be reflected in the guidelines.

PMID- 24939953
TI  - Effect of strabismus surgery on the reading ability of school-age children.
AB  - AIM: To evaluate if strabismus surgery on children between the ages 5 and 14
      years leads to an improvement in reading ability by comparing reading performance
      of patients before and after surgery. METHODS: Pre- and postoperatively, the
      visual acuity, ocular alignment, and stereoacuity of 15 children with horizontal
      strabismus was recorded. The "3-Minute Reading Assessments: Word Recognition,
      Fluency, and Comprehension" for the appropriate age-group were used to assess
      children between the ages of 5 and 14 years. Thirteen of the 15 children
      presented with esotropic deviation, and the remaining 2 were exotropic. RESULTS:
      Postoperatively, 12 patients were orthophoric and 3 had significant residual
      esotropia. The 15 patients had an average improvement in reading speed (10.3
      words per minute), accuracy (4%), and fluency (2 points). For the 12 orthophoric
      patients, reading speed increased by 12.2 (P = .003), accuracy by 3% (P = .064),
      and fluency by 1.33 (P = .006). CONCLUSION: Corrective strabismus surgery in
      school-age children showed an early improvement in reading ability that could
      translate into better academic performance. Our results suggest that reading
      ability could be an important factor when considering corrective surgery for
      children with strabismus.

PMID- 24939951
TI  - Clinical significance and prevalence of valvular strands during routine echo
      examinations.
AB  - AIMS: Lambl's excrescences (valvular strands) have been associated with an
      increased embolic risk. In previous studies, valvular strands have mostly been
      detected by transoesophageal echo (TEE). The current high-resolution echo systems
      allow better detection of valvular strands often even by transthoracic
      echocardiography (TTE). We attempted to determine the incidence of valvular
      strands during routine echo exams, TTE and/or TEE, and their relation to the
      cardiovascular risk factor, co-morbidities, and outcome. METHODS AND RESULTS:
      Over 21 000 echo exams were performed at our hospital during 2008-12 and were
      searched for reporting of valvular strands. One hundred and fifty such studies
      were identified and the presence of valvular strands was confirmed. These
      patients were then evaluated for clinical characteristics, co-morbidities, and
      outcome, and compared with 150 age- and gender-matched patients without valvular
      strands. Incidence of valvular strands was maximal at age 61-70 (0.94%), and they
      were found more commonly in men than in women, 92 vs. 58, P < 0.00001. Valvular
      strands occurred more often on the aortic than on the mitral valve, 125 vs. 36,
      respectively, P < 0.00001, were more often associated with thickened or calcified
      aortic or mitral valve, and occupied the ventricular side of the aortic valve and
      the atrial side of the mitral valve, P < 0.00001. Embolic events occurred in 40
      of the 150 patients with strands (27%). Valvular strands were not associated with
      increased mortality. CONCLUSION: Valvular strands (Lambl's excrescences) appear
      not to affect life expectancy, but are often associated with
      embolic/cerebrovascular events, are more common in older patients, in men than in
      women, and are more commonly located on the aortic than on the mitral valve.

PMID- 24939952
TI  - Accuracy of prospectively ECG-triggered very low-dose coronary dual-source CT
      angiography using iterative reconstruction for the detection of coronary artery
      stenosis: comparison with invasive catheterization.
AB  - OBJECTIVE: To evaluate the image quality and diagnostic accuracy of very low-dose
      computed tomography (CT) angiography (CTA) for the evaluation of coronary artery
      stenosis. BACKGROUND: Iterative reconstruction (IR) has shown to substantially
      reduce image noise and hence permit the use of very low-dose data acquisition
      protocols in coronary CTA. METHODS: Fifty symptomatic patients with an
      intermediate likelihood for coronary artery disease underwent coronary CTA (heart
      rate: 59 +/- 5 bpm, prospectively ECG-triggered axial acquisition, 100 kV, 160
      mAs, 2 * 128 * 0.6 mm collimation, 60 mL contrast, 6 mL/s) prior to invasive
      coronary angiography. CTA images were reconstructed using both standard filtered
      back projection (FBP) and a raw data-based IR algorithm [Sinogram Affirmed
      Iterative Reconstruction (SAFIRE), Siemens Healthcare]. Subjective image quality
      (four-point Likert scale from 0 = non-diagnostic to 3 = excellent image quality),
      image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), as well
      as the presence of coronary stenosis >50% were independently determined by two
      observers. RESULTS: The mean dose-length product was 46.8 +/- 3.5 mGy cm
      (estimated effective dose 0.66 +/- 0.05 mSv). IR led to significantly improved
      objective image quality compared with FBP (image noise: 41 +/- 12 vs. 49 +/- 11
      HU, P < 0.0001; CNR: 16 +/- 8 vs. 12 +/- 4, P < 0.0001; SNR: 13 +/- 7 vs. 10 +/-
      3, P < 0.0001). Four coronary segments were not evaluable on FBP data, whereas
      all segments showed diagnostic image quality with IR. To detect significant
      coronary stenosis, sensitivity, specificity, positive predictive value, and
      negative predictive value were 69% (11/16), 97% (175/180), 69% (11/16), and 97%
      (175/180) per vessel with FBP data sets, respectively. With IR data sets, the
      corresponding values were 81% (13/16), 97% (178/184), 68% (13/19), and 98%
      (178/181). These differences were not statistically significant (P = 0.617).
      CONCLUSIONS: Raw data-based IR significantly improves image quality in very low
      dose prospectively ECG-triggered coronary dual-source CTA when compared with
      standard reconstruction using FBP.

PMID- 24939958
TI  - Uterine artery embolization for severe symptomatic fibroids: effects on fertility
      and symptoms.

PMID- 24939956
TI  - Live birth rates after IVF are reduced by both low and high progesterone levels
      on the day of human chorionic gonadotrophin administration.
AB  - STUDY QUESTION: Are low serum progesterone levels on the day of human chorionic
      gonadotrophin (hCG) administration detrimental for live birth delivery rates
      during in vitro fertilization (IVF)? SUMMARY ANSWER: Progesterone levels <=0.5
      ng/ml on the day of hCG administration hinder live birth rates. WHAT IS KNOWN
      ALREADY: Fundamental research has shown that the presence of late follicular
      phase progesterone is essential for follicular development, ovulation and
      endometrial receptivity. However, previous studies in patients undergoing ovarian
      stimulation have only assessed if progesterone levels in the higher range are
      detrimental for pregnancy or not. That said, information on the effect of the
      full range of late follicular progesterone on IVF outcomes is still lacking.
      STUDY DESIGN, SIZE, DURATION: This was a retrospective, single-centre cohort
      study with 2723 cycles performed in patients aged between 19 and 36 and
      undergoing controlled ovarian stimulation between January 2006 and March 2012 for
      their first or second attempt of IVF followed by a fresh embryo transfer (ET).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent ovarian
      stimulation using a gonadotrophin-releasing hormone (GnRH) antagonist for
      pituitary down-regulation. Final oocyte maturation was triggered with hCG 36 h
      before oocyte retrieval. On the day of hCG administration, serum progesterone
      evaluation was performed. Live birth delivery rates were compared amongst various
      ordinal and regular progesterone intervals (<=0.50, 0.50-0.75, 0.75-1.00, 1.00
      1.25, 1.25-1.50, >1.50 ng/ml) using logistic regression. MAIN RESULTS AND THE
      ROLE OF CHANCE: The average age of our sample was 30.5 years. Almost 82% of all
      embryo transfers were of a single embryo and 51.8% were performed with a Day 5
      embryo. The average value (+/-standard deviation) of progesterone on the day of
      hCG administration was 1.02 +/- 0.50 ng/ml and the live birth rate was 23.4%. The
      live birth rates (according to the above-described ordinal serum progesterone
      intervals) were 17.1, 25.1, 26.7, 25.5, 21.9 and 16.6%, respectively. The live
      birth rates were significantly lower in patients with both low (<=0.5 ng/ml) and
      high (>1.5 ng/ml) late follicular progesterone levels (P < 0.05). LIMITATIONS,
      REASONS FOR CAUTION: The main limitation of our study was its retrospective
      nature. Furthermore, our study was restricted to patients under GnRH antagonist
      pituitary suppression and requires confirmation in a GnRH agonist setting. WIDER
      IMPLICATIONS OF THE FINDINGS: This study comprehensively assessed the
      relationship between live birth delivery rates and progesterone levels on the day
      of hCG administration during ovarian stimulation for IVF. Clinically relevant
      lower (<=0.5 ng/ml) and higher (>1.5 ng/ml) progesterone level limits were
      determined. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this
      study and the authors have no conflicts of interest to declare.

PMID- 24939954
TI  - Restoration of ovarian function and natural fertility following the
      cryopreservation and autotransplantation of whole adult sheep ovaries.
AB  - STUDY QUESTION: Is it possible to restore ovarian function and natural fertility
      following the cryopreservation and autotransplantation of whole ovaries, complete
      with vascular pedicle, in adult females from a large monovulatory animal model
      species (i.e. sheep)? SUMMARY ANSWER: Full (100%) restoration of acute ovarian
      function and high rates of natural fertility (pregnancy rate 64%; live birth rate
      29%), with multiple live births, were obtained following whole ovary
      cryopreservation and autotransplantation (WOCP&TP) of adult sheep ovaries
      utilizing optimized cryopreservation and post-operative anti-coagulant regimes.
      WHAT IS KNOWN ALREADY: Fertility preservation by WOCP&TP requires successful
      cryopreservation of both the ovary and its vascular supply. Previous work has
      indicated detrimental effects of WOCP&TP on the ovarian follicle population.
      Recent experiments suggest that these deleterious effects can be attributed to an
      acute loss of vascular patency due to clot formation induced by damage to ovarian
      arterial endothelial cells. STUDY DESIGN, SIZE, DURATION: Study 1 (2010-2011; N =
      16) examined the effect of post-thaw perfusion of survival factors (angiogenic,
      antioxidant, anti-apoptotic; n = 7-8) and treatment with aspirin (pre-operative
      versus pre- and post-operative (n = 7-9)) on the restoration of ovarian function
      for 3 months after WOCP&TP. Study 2 (2011-2012; N = 16) examined the effect of
      cryoprotectant (CPA) perfusion time (10 versus 60 min; n = 16) and pre- and post
      operative treatment with aspirin in combination with enoxaparine (Clexane((r)); n
      = 8) or eptifibatide (Integrilin((r)); n = 8) on ovarian function and fertility
      11-23 months after WOCP&TP. PARTICIPANTS/MATERIALS, SETTING, METHODS: Both
      studies utilized mature, parous, Greyface ewes aged 3-6 years and weighing 50-75
      kg. Restoration of ovarian function was monitored by bi-weekly blood sampling and
      display of behavioural oestrus. Blood samples were assayed for gonadotrophins,
      progesterone, anti-Mullerian Hormone and inhibin A. Fertility restoration in
      Study 2 was quantified by pregnancy rate after a 3 month fertile mating period
      and was confirmed by ultrasound, hormonal monitoring and live birth. Ovarian
      function was assessed at sacrifice by ovarian appearance and vascular patency
      (Doppler ultrasound) and by follicular histology. MAIN RESULTS AND THE ROLE OF
      CHANCE: In Study 1, survival factors were found to have no benefit, but the
      inclusion of pre-operative aspirin resulted in four ewes showing acute
      restoration of ovarian function within 3 weeks and a further six ewes showing
      partial restoration. The addition of post-operative aspirin alone had no clear
      benefit. In Study 2, combination of aspirin with additional post-operative anti
      coagulants resulted in total acute restoration of ovarian function in 14/14 ewes
      within 3 weeks of WOCP&TP, with 9/14 ewes becoming pregnant and 4/14 giving birth
      to a total of seven normal lambs. There was no difference between anti-coagulants
      in terms of restoration of reproductive function and fertility. In contrast, the
      duration of CPA perfusion was highly significant with a 60 min perfusion
      resulting in ovaries of normal appearance and function with high rates of
      primordial follicle survival (70%) and an abundant blood supply, whereas ovaries
      perfused for 10 min had either resorbed completely and were vestigial (7/14) or
      were markedly smaller (P < 0.01). It is concluded that both the degree of CPA
      penetration and the maintenance of post-operative vascular patency are critical
      determinants of the success of WOCP&TP. LIMITATIONS, REASONS FOR CAUTION: Before
      application of this technology to fertility preservation patients, it will be
      critical to optimize the CPA perfusion time for different sized human ovaries,
      determine the optimum period and level of anti-coagulant therapy, and confirm the
      normality of offspring derived from this procedure. WIDER IMPLICATIONS OF THE
      FINDINGS: This technology holds promise for the preservation of fertility in
      women. It could also potentially be applied to the cryopreservation of other
      reproductive or even major organs (kidneys) where there are considerable
      difficulties in storing donated tissue. STUDY FUNDING/COMPETING INTERESTS:
      Funding was received from the Medical Research Council, University of Nottingham.
      The authors confirm that they have no conflict of interest in relation to this
      work.

PMID- 24939963
TI  - Plasmid-based shRNA lentiviral particle production for RNAi applications.
AB  - Lentiviral vectors have become mainstream gene transfer vehicles for their
      ability to deliver and integrate into host cells. In RNA interference (RNAi)
      applications, lentiviral constructs constitutively express double-stranded RNA
      molecules, usually as short hairpin RNA (shRNA), enabling long-term gene
      silencing, and, when pseudotyped with a broad host glycoprotein envelope, allow a
      multitude of cell types to be transduced. Their successful use ultimately relies
      on the production of lentiviral particles in high titer and uniformity. Typical
      methods require the transfection of three or more plasmids in which essential
      viral elements have been encoded separated so as to remain replication deficient.
      These transfection procedures are of critical importance; however, methods often
      vary among laboratories, making it difficult to assess the overall efficiency of
      lentiviral particle production. In this report, we focus exclusively on this step
      and compare the overall impact of the commercial transfection reagent FuGENE 6
      with FuGENE HD. We found that FuGENE HD resulted in at least 5-fold improvement
      in viral particle titer as assessed by the p24 standard enzyme-linked
      immunosorbent assay. We present the complete optimized workflow and demonstrate
      this utility in which a single modification of this transfection step improved
      the lentiviral particle production. 

PMID- 24939962
TI  - Effect of boron oxide addition on fibre drawing, mechanical properties and
      dissolution behaviour of phosphate-based glass fibres with fixed 40, 45 and 50
      mol% P2O5.
AB  - Previous studies investigating manufacture of phosphate-based glass fibres from
      glasses fixed with P2O5 content less than 50 mol% showed that continuous
      manufacture without breakage was very difficult. In this study, nine phosphate
      based glass formulations from the system P2O5-CaO-Na2O-MgO-B2O3 were prepared
      with P2O5 contents fixed at 40, 45 and 50 mol%, where Na2O was replaced by 5 and
      10 mol% B2O3 and MgO and CaO were fixed to 24 and 16 mol%, respectively. The
      effect of B2O3 addition on the fibre drawing, fibre mechanical properties and
      dissolution behaviour was investigated. It was found that addition of 5 and 10
      mol% B2O3 enabled successful drawing of continuous fibres from glasses with
      phosphate (P2O5) contents fixed at 40, 45 and 50 mol%. The mechanical properties
      of the fibres were found to significantly increase with increasing B2O3 content.
      The highest tensile strength (1200 +/- 130 MPa) was recorded for 45P2O5-16CaO
      5Na2O-24MgO-10B2O3 glass fibres. The fibres were annealed, and a comparison of
      the mechanical properties and mode of degradation of annealed and non-annealed
      fibres were investigated. A decrease in tensile strength and an increase in
      tensile modulus were observed for the annealed fibres. An assessment of the
      change in mechanical properties of both the annealed and non-annealed fibres was
      performed in phosphate-buffered saline (PBS) at 37C for 28 and 60 days,
      respectively. Initial loss of mechanical properties due to annealing was found to
      be recovered with degradation. The B2O3-containing glass fibres were found to
      degrade at a much slower rate as compared to the non-B2O3-containing fibres. Both
      annealed and non-annealed fibres exhibited a peeling effect of the fibre's outer
      layer during degradation. 

PMID- 24939959
TI  - Reply: uterine artery embolization for severe symptomatic fibroids: effects on
      fertility and symptoms.

PMID- 24939965
TI  - Isidore of Seville, eels and disulfiram.

PMID- 24939961
TI  - Surface modification of porous polycaprolactone/biphasic calcium phosphate
      scaffolds for bone regeneration in rat calvaria defect.
AB  - In this study, polycaprolactone scaffolds fabricated by a salt-leaching process
      were loaded with biphasic calcium phosphate successfully to improve the
      osteoconductivity in bone regeneration. The surface of polycaprolactone/biphasic
      calcium phosphate scaffolds was aminolyzed by 1,6-hexamethylenediamine to
      introduce amino groups onto the surface, which was verified qualitatively by
      ninhyrin staining. Collagen was further immobilized on the aminolyzed porous
      polycaprolactone via N-ethyl-N'-(3-dimethylaminopropy) carbodiimide
      hydrochloride/hydroxy-2,5-dioxopyrolidine-3-sulfonic acid sodium cross-linking.
      The pore size of polycaprolactone/biphasic calcium phosphate-collagen scaffolds
      was 200-300 um, which was suitable for bone in-growth. The X-ray photoelectron
      spectroscopy confirmed the coupling of collagen immobilized on the surface of
      polycaprolactone/biphasic calcium phosphate. In vitro results demonstrated that
      the spreading and viability of MC3T3-E1 cells were remarkably improved in the
      polycaprolactone/biphasic calcium phosphate-collagen scaffolds. The in vivo study
      was carried out by implanting the porous polycaprolactone,
      polycaprolactone/biphasic calcium phosphate, and polycaprolactone/biphasic
      calcium phosphate-collagen to the skulls of rats. Although the addition of
      biphasic calcium phosphate particles in the polycaprolactone scaffolds does not
      have a strong effect on the new bone formation, the immobilization of collagen on
      the polycaprolactone/biphasic calcium phosphate scaffolds significantly improved
      the bone regeneration even though the implantation time was short, 6 weeks. The
      present results provide more evidence that functionalizing polycaprolactone with
      biphasic calcium phosphate and collagen may be a feasible way to improve the
      osteoconduction in bone regeneration. 

PMID- 24939960
TI  - Mesenteric ischaemia following cardiac surgery: the influence of intraoperative
      perfusion parameters.
AB  - OBJECTIVES: Mesenteric ischaemia (MesI) remains a rare but lethal complication
      following cardiac surgery. Previously identified risk factors for MesI mortality
      (age, poor left ventricular (LV) function, cardiopulmonary bypass time and blood
      loss) are non-specific and cannot necessarily be modified. This study aims to
      identify potentially modifiable risk factors for MesI mortality through analysis
      of peri- and intraoperative perfusion data. METHODS: Patients who underwent
      cardiac surgery between 2006 and 2011 at Papworth Hospital were retrospectively
      divided into 3 outcome categories: death caused by MesI; death due to other
      causes and survival to discharge. A published MesI risk calculator was used to
      estimate risk of MesI for each patient and then to create 3 cohorts of matched
      patients from each outcome group. Pre-, intra- and postoperative variables were
      collected and conditional logistic regression methods were used to identify
      parameters associated specifically with MesI deaths after cardiac surgery.
      RESULTS: A total of 10 409 patients underwent cardiac surgery between 2006 and
      2011. The incidence of MesI was 0.3% (30 patients). Two hundred and sixty-one
      patients died of non-MesI causes and 10 118 survived. It was possible to identify
      25 patients in each group at equivalent risk of MesI. The following parameters
      were found to be associated with MesI mortality: recent myocardial infarction
      [odds ratio (OR) 4.98, 95% confidence interval (CI) 1.58-15.71, P = 0.01],
      standard EuroSCORE (OR 1.12, 95% CI 1.03-1.21, P = 0.01), vasopressor dose on
      bypass (OR 1.28, 95% CI 1.04-1.57, P = 0.02), metaraminol dose on bypass (OR
      1.52, 95% CI 1.12-2.06, P = 0.01) and lowest documented mean arterial pressure
      (OR 0.90, 95% CI 0.83-0.97, P = 0.01). No other intraoperative perfusion-related
      parameters (e.g. flow, average activated clotting time or pressure) were
      associated with MesI mortality. CONCLUSIONS: Our study not only confirms
      previously known predictive factors, but also demonstrates a new association
      between intraoperative vasopressor use and MesI mortality.

PMID- 24939957
TI  - Identification of a duplication within the GDF9 gene and novel candidate genes
      for primary ovarian insufficiency (POI) by a customized high-resolution array
      comparative genomic hybridization platform.
AB  - STUDY QUESTION: Can high-resolution array comparative genomic hybridization (CGH)
      analysis of DNA samples from women with primary ovarian insufficiency (POI)
      improve the diagnosis of the condition and identify novel candidate genes for
      POI? SUMMARY ANSWER: A mutation affecting the regulatory region of growth
      differentiation factor 9 (GDF9) was identified for the first time together with
      several novel candidate genes for POI. WHAT IS KNOWN ALREADY: Most patients with
      POI do not receive a molecular diagnosis despite a significant genetic component
      in the pathogenesis. STUDY DESIGN, SIZE, DURATION: We performed a case-control
      study. Twenty-six patients were analyzed by array CGH for identification of copy
      number variants. Novel changes were investigated in 95 controls and in a separate
      population of 28 additional patients with POI. The experimental procedures were
      performed during a 1-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: DNA
      samples from 26 patients with POI were analyzed by a customized 1M array-CGH
      platform with whole genome coverage and probe enrichment targeting 78 genes in
      sex development. By PCR amplification and sequencing, the breakpoint of an
      identified partial GDF9 gene duplication was characterized. A multiplex ligation
      dependent probe amplification (MLPA) probe set for specific identification of
      deletions/duplications affecting GDF9 was developed. An MLPA probe set for the
      identification of additional cases or controls carrying novel candidate regions
      identified by array-CGH was developed. Sequencing of three candidate genes was
      performed. MAIN RESULTS AND THE ROLE OF CHANCE: Eleven unique copy number changes
      were identified in a total of 11 patients, including a tandem duplication of 475
      bp, containing part of the GDF9 gene promoter region. The duplicated region
      contains three NOBOX-binding elements and an E-box, important for GDF9 gene
      regulation. This aberration is likely causative of POI. Fifty-four patients were
      investigated for copy number changes within GDF9, but no additional cases were
      found. Ten aberrations constituting novel candidate regions were detected,
      including a second DNAH6 deletion in a patient with POI. Other identified
      candidate genes were TSPYL6, SMARCC1, CSPG5 and ZFR2. LIMITATIONS, REASONS FOR
      CAUTION: This is a descriptive study and no functional experiments were
      performed. WIDER IMPLICATIONS OF THE FINDINGS: The study illustrates the
      importance of analyzing small copy number changes in addition to sequence
      alterations in the genetic investigation of patients with POI. Also, promoter
      regions should be included in the investigation. STUDY FUNDING/COMPETING
      INTERESTS: The study was supported by grants from the Swedish Research council
      (project no 12198 to A.W. and project no 20324 to A.L.H.), Stockholm County
      Council (E.I., A.W. and K.R.W.), Foundation Frimurare Barnhuset (A.N., A.W. and
      M.B.), Karolinska Institutet (A.N., A.L.H., E.I., A.W. and M.B.), Novo Nordic
      Foundation (A.W.) and Svenska Lakaresallskapet (M.B.). The funding sources had no
      involvement in the design or analysis of the study. The authors have no competing
      interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 24939955
TI  - Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal
      endometrium and in endometriosis.
AB  - STUDY QUESTION: Are the transmembrane mucins, MUC1, MUC4 and MUC16,
      differentially expressed in endometriosis compared with normal endometrium?
      SUMMARY ANSWER: This study revealed that transmembrane mucin expression does not
      vary significantly in normal endometrium during the menstrual cycle and is not
      altered in endometriosis relative to the epithelial marker, cytokeratin-18
      (KRT18). WHAT IS KNOWN ALREADY: Increased serum levels of the transmembrane mucin
      fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of
      simple epithelia are found in several pathological conditions, including
      endometriosis. Altered mucin expression in gynecologic diseases may promote
      infertility or endometrial pathologies. STUDY DESIGN, SIZE, DURATION: This was a
      laboratory-based study of samples from 12 endometriosis patients as well as non
      endometriosis control samples obtained from 31 patients. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Total RNA was isolated from endometrial biopsies of ectopic and
      eutopic endometrium from women with endometriosis and control patients from
      different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were
      performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial
      marker, cytokeratin-18 (KRT18), or beta-actin (ACTB). Frozen sections from
      endometrial biopsies of proliferative and mid-secretory stage women with
      endometriosis were immunostained for MUC1, MUC4 and MUC16. MAIN RESULTS AND THE
      ROLE OF CHANCE: qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these
      mucins do not vary significantly during the menstrual cycle nor are they altered
      in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA
      is expressed at very low levels relative to MUC1 and MUC16 under all conditions.
      There was little difference in MUC1 and MUC16 expression between eutopic
      endometrial and ectopic endometriotic tissues. MUC4 expression also was not
      significantly higher in the ectopic endometriotic tissues. Immunostaining for all
      three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces
      of endometrial epithelia, but little to no staining for MUC4. LIMITATIONS,
      REASONS FOR CAUTION: qRT-PCR analysis was the main method used for mucin
      detection. Additional studies with stage III-IV endometriotic tissue would be
      useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4
      expression increases, at later stages of endometriosis. WIDER IMPLICATIONS OF THE
      FINDINGS: We report a comprehensive comparative profile of the major
      transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker,
      KRT18, in normal cycling endometrium and in endometriosis, and indicate
      constitutive expression. Previous studies have profiled the expression of
      individual mucins relative to beta-actin and indicate accumulation in the luteal
      phase. Thus, these differences in interpretation appear to reflect the increased
      epithelial content of endometrium during the luteal phase. STUDY FUNDING: This
      study was supported by: NIH R01HD29963 to D.D.C.; NIH U54HD007495 to S.M.H.; and
      NIH R01HD067721 to S.L.Y. and B.A.L. The authors have no competing interests to
      declare.

PMID- 24939964
TI  - Utilization of baclofen in maintenance of alcohol abstinence in patients with
      alcohol dependence and alcoholic hepatitis with or without cirrhosis.
AB  - AIM: To report the efficacy and safety of baclofen in improving clinical state in
      patients with alcoholic hepatitis. METHOD: Single center, open, retrospective
      study analyzing the effects of baclofen utilized over 12 months in patients with
      alcoholic hepatitis with or without cirrhosis and alcohol dependence on these
      liver parameters: aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), total bilirubin (Tbili), prothrombin time (PT), international normalized
      ratio (INR), albumin and Model for End-Stage Liver Disease (MELD) score. RESULTS:
      Out of 40 patients, 35 were treated with baclofen. On average, baclofen was used
      for 5.8 months. A significant decrease in the mean AST, ALT, Tbili, INR, PT and
      MELD score was seen when comparing pre-baclofen use compared with post-baclofen
      use. Of the 35 patients who were started on baclofen, 34 (97%) remained
      abstinent. There were no serious adverse events. CONCLUSIONS: Baclofen's safety
      and efficacy in improving the clinical condition patients with alcoholic liver
      disease has been supported. Randomized prospective studies with longer duration
      of baclofen in this population may further optimize its use and corroborate
      efficacy.

PMID- 24939968
TI  - Towards the future.

PMID- 24939969
TI  - Scientific misconduct and ethical aspects in publishing.

PMID- 24939967
TI  - On the importance of health monitoring.

PMID- 24939975
TI  - Giant cerebral cysticercosis.

PMID- 24939970
TI  - Examining the potential of information technology to improve public insurance
      application processes: enrollee assessments from a concurrent mixed method
      analysis.
AB  - OBJECTIVE: To assess the perceived readiness of Medicaid and Children's Health
      Insurance Program (CHIP) enrollees to use information technologies (IT) in order
      to facilitate improvements in the application processes for these public
      insurance programs. METHODS: We conducted a concurrent mixed method study of
      Medicaid and CHIP enrollees in a southern state. We conducted focus groups to
      identify enrollee concerns regarding the current application process and their IT
      proficiency. Additionally, we surveyed beneficiaries via telephone about their
      access to and use of the Internet, and willingness to adopt IT-enabled processes.
      2013 households completed the survey. We used chi(2) analysis for comparisons
      across different groups of respondents. RESULTS: A majority of enrollees will
      embrace IT-enabled enrollment, but a small yet significant group continues to
      lack access to facilitating technologies. Moreover, a segment of beneficiaries in
      the two programs continues to place a high value on personal interactions with
      program caseworkers. DISCUSSION: IT holds the promise of improving efficiency and
      reducing barriers for enrollees, but state and federal agencies managing public
      insurance programs need to ensure access to traditional processes and make
      caseworkers available to those who require and value such assistance, even after
      implementing IT-enabled processes. CONCLUSIONS: The use of IT-enabled processes
      is essential for effectively managing eligibility and enrollment determinations
      for public programs and private plans offered through state or federally operated
      exchanges. However, state and federal officials should be cognizant of the
      technological readiness of recipients and provide offline help to ensure broad
      participation in the insurance market.

PMID- 24939972
TI  - Moyamoya syndrome with antiphospholipid antibodies: a case report and literature
      review.
AB  - Moyamoya syndrome is a term applied to typical moyamoya vasculopathy with well
      recognized associated conditions. Several systematic studies on the entities of
      moyamoya syndrome with autoimmune disease have been reported. We report a case of
      moyamoya syndrome with antiphospholipid antibodies and provide a review of
      relevant cases from the literature, describing the clinical characteristics and
      treatments.

PMID- 24939971
TI  - Cognitive Profiles of Mathematical Problem Solving Learning Disability for
      Different Definitions of Disability.
AB  - Three cohorts of third-grade students (N= 813) were evaluated on achievement,
      cognitive abilities, and behavioral attention according to contrasting research
      traditions in defining math learning disability (LD) status: low achievement
      versus extremely low achievement and IQ-achievement discrepant versus strictly
      low-achieving LD. We use methods from these two traditions to form math problem
      solving LD groups. To evaluate group differences, we used MANOVA-based profile
      and canonical analyses to control for relations among the outcomes and regression
      to control for group definition variables. Results suggest that basic arithmetic
      is the key distinguishing characteristic that separates low-achieving problem
      solvers (including LD, regardless of definition) from typically achieving
      students. Word problem solving is the key distinguishing characteristic that
      separates IQ-achievement-discrepant from strictly low-achieving LD students,
      favoring the IQ-achievement-discrepant students. 

PMID- 24939973
TI  - Characteristics of brain stem auditory evoked potentials in children with hearing
      impairment due to infectious diseases.
AB  - Among objective audiologic tests, the most important were tests of brain stem
      auditory evoked potentials. The objective of the study was to test the
      configuration, degree of hearing loss, and response characteristics of auditory
      brain stem evoked potentials in children with hearing loss occurred due to
      infectious disease. A case control study design was used. The study group
      consisted of 54 patients referred for a hearing test because of infectious
      diseases caused by other agents or that occurred as congenital infection.
      Infectious agents have led to the emergence of various forms of sensorineural
      hearing loss. We have found deviations from the normal values of absolute and
      interwave latencies in some children in our group. We found that in the group of
      children who had the diseases such as purulent meningitis, or were born with
      rubella virus and cytomegalovirus infection, a retrocochlear damage was present
      in children with and without cochlear damage. 

PMID- 24939983
TI  - The future is NICE!

PMID- 24939985
TI  - Practice observed.

PMID- 24939979
TI  - Cylus et al. respond to "unrealized benefits?".

PMID- 24939989
TI  - Would Fred Sanger get funded today?
AB  - Fred Sanger developed technologies that won him two Nobel Prizes and
      revolutionized biological research. Yet, in spite of this record, the question
      has been raised as to whether, in the current scientific climate, he might be
      unsuccessful in obtaining a grant because of a productivity that would be viewed
      as too limited. In imagining how a National Institutes of Health study section
      today might treat a proposal from Sanger to sequence DNA, we can ask whether
      there are lessons from his career that suggest changes to the grant review
      process. 

PMID- 24939974
TI  - Growth hormone deficiency in a dopa-responsive dystonia patient with a novel
      mutation of guanosine triphosphate cyclohydrolase 1 gene.
AB  - Dopa-responsive dystonia is a rare hereditary movement disorder caused by
      mutations in the guanosine triphosphate cyclohydrolase 1 (GCH1) gene. This
      disease typically manifests in dystonia, with marked diurnal fluctuation and a
      dramatic response to levodopa. However, growth retardation in dopa-responsive
      dystonia has rarely been reported, and the etiology of short stature is not
      clarified. Here, we report a 14-year-old patient with extremities dystonia and
      short stature. Treatment with levodopa relieved his symptoms and resulted in a
      height increase. We also investigated the mutation in GCH1 and the etiology of
      short stature in this case. Sequence analysis of GCH1 revealed a novel mutation
      (c.695G>T). Laboratory examinations and imaging confirmed the diagnosis of growth
      hormone deficiency. We conclude that our case reveals a rare feature for dopa
      responsive dystonia and suggests a possible pathogenic link between growth
      hormone deficiency and dopa-responsive dystonia. We recommend levodopa as the
      first choice for treating dopa-responsive dystonia in children with growth
      hormone deficiency. 

PMID- 24939986
TI  - The travelling patient: a clinician's guide to the law surrounding medical
      tourism.
AB  - European law stipulates that all patients in the European Union (EU) have the
      right to seek state-funded healthcare in other EU nations as if they were being
      treated in their home country. This means they should not incur additional costs
      for their home country's healthcare system. In cases of clinical negligence,
      patients are unlikely to bring a successful claim against the National Health
      Service (NHS). They face additional challenges if they bring the foreign service
      provider to an English court; they would need to establish jurisdiction, the
      applicable law, and enforce a successful judgment. The NHS may have to bear the
      cost of corrective treatment which is unlikely to be fully restorative.
      Clinicians need to be aware of the law so that they can reach a shared decision
      with the patient which takes into consideration the risks to the patient and
      service provision within the NHS. 

PMID- 24939982
TI  - Simply scan--optical methods for elemental carbon measurement in diesel exhaust
      particulate.
AB  - This article describes a performance assessment of three optical methods, a Magee
      Scientific OT21 Transmissometer, a Hach-Lange Microcolor II difference gloss
      meter, and a combination of an office scanner with Adobe Photoshop software. The
      optical methods measure filter staining as a proxy for elemental carbon in diesel
      exhaust particulate (DEP) exposure assessment and the suitability of each as a
      replacement for the existing Bosch meter optical method. Filters loaded with DEP
      were produced from air in a non-coal mine and the exhaust gases from a mobile
      crane. These were measured with each apparatus and then by combustion to obtain a
      reference elemental carbon value. The results from each apparatus were then
      plotted against both the Bosch number and reference elemental carbon values. The
      equations of the best fit lines for these plots were derived, and these gave
      functions for elemental carbon and Bosch number from the output of each new
      optical method. For each optical method, the range of DEP loadings which can be
      measured has been determined, and conversion equations for elemental carbon and
      Bosch number have been obtained. All three optical methods studied will
      effectively quantify blackness as a measure of elemental carbon. Of these the
      Magee Scientific OT21 transmissometer has the best performance. The Microcolor II
      and scanner/photoshop methods will in addition allow conversion to Bosch number
      which may be useful if historical Bosch data are available and functions for this
      are described. The scanner/photoshop method demonstrates a technique to obtain
      measurements of DEP exposure without the need to purchase specialized
      instrumentation. 

PMID- 24939981
TI  - Invited commentary: are there unrealized benefits of unemployment insurance among
      the employed?
AB  - Political statements about the relationship between the economy and health
      intensify during economic downturns and fade in times of prosperity. Population
      health researchers share this cyclical interest in that the numbers of peer
      reviewed publications on this topic increase during and immediately after
      recessions. In this issue of the Journal, Cylus et al. (Am J Epidemiol.
      2014;180(1):45-52) follow in the "economy and health" research tradition and
      examine the relationship between US unemployment rates and suicide mortality.
      Their work makes a novel contribution in that they examine whether generous
      unemployment insurance benefits attenuate the relationship between economic
      downturns and suicide mortality in the United States. In this commentary, I
      assess the internal validity of their analysis, call into question some
      assumptions of their approach, and place their contribution within the context of
      the broader literature. I then argue that population-based and individual-based
      approaches in the "economy and health" field often work in concert to create
      knowledge and inform policy-makers. 

PMID- 24939977
TI  - The role of proximal circumstances and child behaviour in toddlers' risk for
      minor unintentional injuries.
AB  - BACKGROUND: Much of the research on child injury risk has focused on trait-like
      factors (eg, hyperactivity, child gender) that influence injury risk rather than
      state-like factors (eg, environmental circumstances, child behaviour). Additional
      research is needed to better identify the proximal risk factors for children's
      risk for unintentional injury. OBJECTIVES: The present study examined the
      antecedents to minor unintentional injury events and whether unusual
      circumstances and child behaviour predicted injury risk. METHODS: The study used
      archival data that were collected via biweekly in-person interviews with 170
      mothers of toddlers (15-36 months) for 6 months. A case crossover design was used
      to predict children's risk for injury from proximal risk factors. RESULTS:
      Children were at a higher risk for injury when circumstances were unusual and
      when they were engaging in an unusual behaviour. When a child was engaging in an
      unusual behaviour, higher levels of maternal supervision predicted lower injury
      risk. Children were more likely to be injured in a new environment, in an
      environment with animals or other people, in an environment with hazards or when
      engaging in a new activity or in a familiar activity performed in an unfamiliar
      way. CONCLUSIONS: The results indicate that toddlers may be at a greater risk for
      minor unintentional injury when environmental circumstances are outside of the
      norm or when a child is engaging in unusual behaviours. The findings also
      indicate that higher levels of caregiver supervision may be especially beneficial
      when children are engaging in new or unfamiliar activities.

PMID- 24939987
TI  - PDF neuron firing phase-shifts key circadian activity neurons in Drosophila.
AB  - Our experiments address two long-standing models for the function of the
      Drosophila brain circadian network: a dual oscillator model, which emphasizes the
      primacy of PDF-containing neurons, and a cell-autonomous model for circadian
      phase adjustment. We identify five different circadian (E) neurons that are a
      major source of rhythmicity and locomotor activity. Brief firing of PDF cells at
      different times of day generates a phase response curve (PRC), which mimics a
      light-mediated PRC and requires PDF receptor expression in the five E neurons.
      Firing also resembles light by causing TIM degradation in downstream neurons.
      Unlike light however, firing-mediated phase-shifting is CRY-independent and
      exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our
      results suggest that PDF neurons integrate light information and then modulate
      the phase of E cell oscillations and behavioral rhythms. The results also explain
      how fly brain rhythms persist in constant darkness and without CRY. 

PMID- 24939976
TI  - Effects of caffeine treatment for apnea of prematurity on cortical speech-sound
      differentiation in preterm infants.
AB  - Caffeine, standard treatment for apnea of prematurity, improves brainstem
      auditory processing. We hypothesized that caffeine also improves cortical
      differentiation of complex speech sounds. We used event-related potential
      methodology to measure responses to speech-sound contrasts in 45 intensive care
      neonates, stratified by cumulative exposure as no-, low-, and high-caffeine
      groups. Sound differentiation in the low-caffeine group and near-term no-caffeine
      infants was similar with repeated measures analysis of variance controlling for
      gestational and postnatal age. However, a generalized estimating equation
      approach demonstrated that, at equivalent postnatal age, differentiation was
      reduced in the high-caffeine (gestational age 25 weeks) compared to the low
      caffeine group (gestational age 28 weeks), reflecting the importance of maturity
      at birth (Z = 2.77, P < .006). We conclude that caffeine improves measures of
      auditory processing associated with improved neurodevelopmental outcomes in
      preterm infants. However, current usage of caffeine for apnea of prematurity
      cannot fully compensate for the effects of brain immaturity on speech sound
      processing. 

PMID- 24939990
TI  - The genetic control of apomixis: asexual seed formation.
AB  - Apomixis (asexual seed formation) is the result of a plant gaining the ability to
      bypass the most fundamental aspects of sexual reproduction: meiosis and
      fertilization. Without the need for male fertilization, the resulting seed
      germinates a plant that develops as a maternal clone. This dramatic shift in
      reproductive process has been documented in many flowering plant species,
      although no major seed crops have been shown to be capable of apomixis. The
      ability to generate maternal clones and therefore rapidly fix desirable genotypes
      in crop species could accelerate agricultural breeding strategies. The potential
      of apomixis as a next-generation breeding technology has contributed to
      increasing interest in the mechanisms controlling apomixis. In this review, we
      discuss the progress made toward understanding the genetic and molecular control
      of apomixis. Research is currently focused on two fronts. One aims to identify
      and characterize genes causing apomixis in apomictic species that have been
      developed as model species. The other aims to engineer or switch the sexual seed
      formation pathway in non-apomictic species, to one that mimics apomixis. Here we
      describe the major apomictic mechanisms and update knowledge concerning the loci
      that control them, in addition to presenting candidate genes that may be used as
      tools for switching the sexual pathway to an apomictic mode of reproduction in
      crops. 

PMID- 24939978
TI  - Do generous unemployment benefit programs reduce suicide rates? A state fixed
      effect analysis covering 1968-2008.
AB  - The recent economic recession has led to increases in suicide, but whether US
      state unemployment insurance programs ameliorate this association has not been
      examined. Exploiting US state variations in the generosity of benefit programs
      between 1968 and 2008, we tested the hypothesis that more generous unemployment
      benefit programs reduce the impact of economic downturns on suicide. Using state
      linear fixed-effect models, we found a negative additive interaction between
      unemployment rates and benefits among the US working-age (20-64 years) population
      (beta = -0.57, 95% confidence interval: -0.86, -0.27; P < 0.001). The finding of
      a negative additive interaction was robust across multiple model specifications.
      Our results suggest that the impact of unemployment rates on suicide is offset by
      the presence of generous state unemployment benefit programs, though estimated
      effects are small in magnitude. 

PMID- 24939988
TI  - Evolution of histone 2A for chromatin compaction in eukaryotes.
AB  - During eukaryotic evolution, genome size has increased disproportionately to
      nuclear volume, necessitating greater degrees of chromatin compaction in higher
      eukaryotes, which have evolved several mechanisms for genome compaction. However,
      it is unknown whether histones themselves have evolved to regulate chromatin
      compaction. Analysis of histone sequences from 160 eukaryotes revealed that the
      H2A N-terminus has systematically acquired arginines as genomes expanded.
      Insertion of arginines into their evolutionarily conserved position in H2A of a
      small-genome organism increased linear compaction by as much as 40%, while their
      absence markedly diminished compaction in cells with large genomes. This effect
      was recapitulated in vitro with nucleosomal arrays using unmodified histones,
      indicating that the H2A N-terminus directly modulates the chromatin fiber likely
      through intra- and inter-nucleosomal arginine-DNA contacts to enable tighter
      nucleosomal packing. Our findings reveal a novel evolutionary mechanism for
      regulation of chromatin compaction and may explain the frequent mutations of the
      H2A N-terminus in cancer. 

PMID- 24939980
TI  - Marginal structural Cox models for estimating the association between beta
      interferon exposure and disease progression in a multiple sclerosis cohort.
AB  - Longitudinal observational data are required to assess the association between
      exposure to beta-interferon medications and disease progression among relapsing
      remitting multiple sclerosis (MS) patients in the "real-world" clinical practice
      setting. Marginal structural Cox models (MSCMs) can provide distinct advantages
      over traditional approaches by allowing adjustment for time-varying confounders
      such as MS relapses, as well as baseline characteristics, through the use of
      inverse probability weighting. We assessed the suitability of MSCMs to analyze
      data from a large cohort of 1,697 relapsing-remitting MS patients in British
      Columbia, Canada (1995-2008). In the context of this observational study, which
      spanned more than a decade and involved patients with a chronic yet fluctuating
      disease, the recently proposed "normalized stabilized" weights were found to be
      the most appropriate choice of weights. Using this model, no association between
      beta-interferon exposure and the hazard of disability progression was found
      (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity
      analyses, truncated normalized unstabilized weights were used in additional MSCMs
      and to construct inverse probability weight-adjusted survival curves; the
      findings did not change. Additionally, qualitatively similar conclusions from
      approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence
      in the findings. 

PMID- 24939992
TI  - The genetics of immunity.

PMID- 24939993
TI  - The genetics of sex: exploring differences.

PMID- 24939991
TI  - The yeast deletion collection: a decade of functional genomics.
AB  - The yeast deletion collections comprise >21,000 mutant strains that carry precise
      start-to-stop deletions of ~6000 open reading frames. This collection includes
      heterozygous and homozygous diploids, and haploids of both MAT A: and MATalpha
      mating types. The yeast deletion collection, or yeast knockout (YKO) set,
      represents the first and only complete, systematically constructed deletion
      collection available for any organism. Conceived during the Saccharomyces
      cerevisiae sequencing project, work on the project began in 1998 and was
      completed in 2002. The YKO strains have been used in numerous laboratories in
      >1000 genome-wide screens. This landmark genome project has inspired development
      of numerous genome-wide technologies in organisms from yeast to man. Notable
      spinoff technologies include synthetic genetic array and HIPHOP chemogenomics. In
      this retrospective, we briefly describe the yeast deletion project and some of
      its most noteworthy biological contributions and the impact that these
      collections have had on the yeast research community and on genomics in general.

PMID- 24939995
TI  - Estimating tempo and mode of Y chromosome turnover: explaining Y chromosome loss
      with the fragile Y hypothesis.
AB  - Chromosomal sex determination is phylogenetically widespread, having arisen
      independently in many lineages. Decades of theoretical work provide predictions
      about sex chromosome differentiation that are well supported by observations in
      both XY and ZW systems. However, the phylogenetic scope of previous work gives us
      a limited understanding of the pace of sex chromosome gain and loss and why Y or
      W chromosomes are more often lost in some lineages than others, creating XO or ZO
      systems. To gain phylogenetic breadth we therefore assembled a database of 4724
      beetle species' karyotypes and found substantial variation in sex chromosome
      systems. We used the data to estimate rates of Y chromosome gain and loss across
      a phylogeny of 1126 taxa estimated from seven genes. Contrary to our initial
      expectations, we find that highly degenerated Y chromosomes of many members of
      the suborder Polyphaga are rarely lost, and that cases of Y chromosome loss are
      strongly associated with chiasmatic segregation during male meiosis. We propose
      the "fragile Y" hypothesis, that recurrent selection to reduce recombination
      between the X and Y chromosome leads to the evolution of a small pseudoautosomal
      region (PAR), which, in taxa that require XY chiasmata for proper segregation
      during meiosis, increases the probability of aneuploid gamete production, with Y
      chromosome loss. This hypothesis predicts that taxa that evolve achiasmatic
      segregation during male meiosis will rarely lose the Y chromosome. We discuss
      data from mammals, which are consistent with our prediction. 

PMID- 24939994
TI  - Pseudosynapsis and decreased stringency of meiotic repair pathway choice on the
      hemizygous sex chromosome of Caenorhabditis elegans males.
AB  - During meiosis, accurate chromosome segregation relies on homology to mediate
      chromosome pairing, synapsis, and crossover recombination. Crossovers are
      dependent upon formation and repair of double-strand breaks (DSBs) by homologous
      recombination (HR). In males of many species, sex chromosomes are largely
      hemizygous, yet DSBs are induced along nonhomologous regions. Here we analyzed
      the genetic requirements for meiotic DSB repair on the completely hemizygous X
      chromosome of Caenorhabditis elegans males. Our data reveal that the kinetics of
      DSB formation, chromosome pairing, and synapsis are tightly linked in the male
      germ line. Moreover, DSB induction on the X is concomitant with a brief period of
      pseudosynapsis that may allow X sister chromatids to masquerade as homologs.
      Consistent with this, neither meiotic kleisins nor the SMC-5/6 complex are
      essential for DSB repair on the X. Furthermore, early processing of X DSBs is
      dependent on the CtIP/Sae2 homolog COM-1, suggesting that as with paired
      chromosomes, HR is the preferred pathway. In contrast, the X chromosome is
      refractory to feedback mechanisms that ensure crossover formation on autosomes.
      Surprisingly, neither RAD-54 nor BRC-2 are essential for DSB repair on the X,
      suggesting that unlike autosomes, the X is competent for repair in the absence of
      HR. When both RAD-54 and the structure-specific nuclease XPF-1 are abrogated, X
      DSBs persist, suggesting that single-strand annealing is engaged in the absence
      of HR. Our findings indicate that alteration in sister chromatid interactions and
      flexibility in DSB repair pathway choice accommodate hemizygosity on sex
      chromosomes.

PMID- 24939997
TI  - Skeletal muscle lipid content and oxidative activity in relation to muscle fiber
      type in aging and metabolic syndrome.
AB  - One of the most noticeable effects of aging is the reduction in skeletal muscle
      mass and strength (sarcopenia). The metabolic syndrome (MS) is also prevalent in
      old subjects, but its relevance to skeletal muscle characteristics has poorly
      been investigated. Immunohistochemical studies were performed with muscle
      biopsies from young (22 years) and old (73 years) men with and without MS to
      reveal age-dependent and MS-associated modifications of fiber-type
      characteristics. Atrophy of type II fibers and altered fiber shape characterized
      muscle aging in lean healthy men. In contrast, increased cross-sectional area of
      the most abundant type I and type IIA fibers, and reduced cytochrome c oxidase
      content in all fiber types, characterized MS. Aging and particularly MS were
      associated with accumulation of intramyocellular lipid droplets. Although lipids
      mostly accumulated in type I fibers, matrix-assisted laser desorption/ionization
      mass spectrometry imaging of intramyocellular lipids did not distinguish fiber
      types, but clearly separated young, old, and MS subjects. In conclusion, our
      study suggests that MS in the elderly persons is associated with alterations in
      skeletal muscle at a fiber-type specific level. Overall, these fiber type
      specific modifications may be important both for the age-related loss of muscle
      mass and strength and for the increased prevalence of MS in elderly subjects. 

PMID- 24939998
TI  - Continuity and innovation in the data collection protocols of the second Wave of
      the National Social Life, Health, and Aging Project.
AB  - BACKGROUND: The second Wave (W2) of the National Social Life, Health, and Aging
      Project (NSHAP), a nationally representative, longitudinal survey of older adults
      now between the ages of 62 and 90, conducted approximately 3,400 interviews.
      Selected coresidential romantic partners as well as W1 panel nonrespondents were
      selected for W2. Data collection included in-person questionnaires, up to 15
      biomeasures, and a post-interview questionnaire. METHODS: A proxy questionnaire
      also collected data on respondents that were deceased or in too poor health to
      participate in W2. Biomeasure collection included height, weight, hip and waist
      circumference, blood pressure, heart rate, and preventricular contraction, timed
      walk and chair stands, smell, saliva collection using a Salivette (cortisol),
      saliva passive drool in a tube (dehydroepiandrosterone, estradiol, progesterone,
      testosterone), dried blood spots (Epstein-Barr virus antibody titers, C-reactive
      protein, glycosylated hemoglobin, hemoglobin, cholesterol, high-density
      lipoprotein), whole blood in a microtainer (cytokines), urine (creatinine,
      vasopressin, oxytocin), Oragene (genotype), respondent-administered vaginal swabs
      (bacterial vaginosis,yeast, and vaginal cell cytology), and Actiwatch (sleep
      patterns and activity). RESULTS: Measures, such as response and cooperation
      rates, are also provided to evaluate design and implementation. DISCUSSION: This
      article describes both innovation in the development and implementation of W2 as
      well as fidelity to W1 study design and data collection procedures.

PMID- 24939999
TI  - The Seniors' Outdoor Survey: An Observational Tool for Assessing Outdoor
      Environments at Long-Term Care Settings.
AB  - PURPOSE OF THE STUDY: To describe the development and psychometric testing of the
      Seniors' Outdoor Survey (SOS), an instrument for evaluating how well the outdoor
      space in a long-term care setting supports the preferences and outdoor usage of
      residents. DESIGN AND METHODS: Content validity of the main SOS items initially
      was based on relevant literature and preliminary studies in diverse long-term
      care settings. After conducting a multiregional pilot study with 152 outdoor
      spaces at 68 assisted living facilities, the instrument was substantially revised
      and tested for interrater and test-retest reliability with 22 outdoor spaces at
      12 long-term care settings, using 2 raters. Validity was examined using content
      analysis of resident survey responses (N = 1,128) from the multiregional study
      and specific item validation by subject matter experts (N = 53). RESULTS: The
      final instrument contains 60 ratable items organized in 5 domains: access to
      nature (14 items), outdoor comfort and safety (15 items), walking and outdoor
      activities (14 items), indoor-outdoor connection (11 items), and connection to
      the world (6 items). Intraclass correlation coefficient (ICC) estimates of
      interrater reliability were .91 for the overall instrument, ranging from .83 to
      .98 for the 5 domains. Interrater reliability (ICC) was above .70 for more than
      79% of individual items. Test-retest reliability (ICC) was .92, ranging from .81
      to .98 for domains. IMPLICATIONS: The SOS tool fills a gap in the available
      environmental assessment instruments, providing a reliable way for researchers,
      providers, and designers to evaluate and compare the supportive potential of
      outdoor spaces for long-term care residents.

PMID- 24940001
TI  - To protect or reject.
AB  - A protein known for its role in dismantling faulty SNARE complexes can also help
      to maintain complexes that have formed properly during membrane fusion. 

PMID- 24940002
TI  - The ins and outs of breathing.
AB  - Distinct populations of neurons within the brainstem are responsible for
      generating and coordinating the rhythmic patterns of neural activity that
      underlie breathing. 

PMID- 24940000
TI  - tRNA synthetase counteracts c-Myc to develop functional vasculature.
AB  - Recent studies suggested an essential role for seryl-tRNA synthetase (SerRS) in
      vascular development. This role is specific to SerRS among all tRNA synthetases
      and is independent of its well-known aminoacylation function in protein
      synthesis. A unique nucleus-directing domain, added at the invertebrate-to
      vertebrate transition, confers this novel non-translational activity of SerRS.
      Previous studies showed that SerRS, in some unknown way, controls VEGFA
      expression to prevent vascular over-expansion. Using in vitro, cell and animal
      experiments, we show here that SerRS intervenes by antagonizing c-Myc, the major
      transcription factor promoting VEGFA expression, through a tandem mechanism.
      First, by direct head-to-head competition, nuclear-localized SerRS blocks c-Myc
      from binding to the VEGFA promoter. Second, DNA-bound SerRS recruits the SIRT2
      histone deacetylase to erase prior c-Myc-promoted histone acetylation. Thus,
      vertebrate SerRS and c-Myc is a pair of 'Yin-Yang' transcriptional regulator for
      proper development of a functional vasculature. Our results also discover an anti
      angiogenic activity for SIRT2.DOI: http://dx.doi.org/10.7554/eLife.02349.001. 

PMID- 24940003
TI  - The CD2 isoform of protocadherin-15 is an essential component of the tip-link
      complex in mature auditory hair cells.
AB  - Protocadherin-15 (Pcdh15) is a component of the tip-links, the extracellular
      filaments that gate hair cell mechano-electrical transduction channels in the
      inner ear. There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only
      differ by their cytoplasmic domains; they are thought to function redundantly in
      mechano-electrical transduction during hair-bundle development, but whether any
      of these isoforms composes the tip-link in mature hair cells remains unknown. By
      immunolabelling and both morphological and electrophysiological analyses of post
      natal hair cell-specific conditional knockout mice (Pcdh15ex38-fl/ex38-fl Myo15
      cre+/-) that lose only this isoform after normal hair-bundle development, we show
      that Pcdh15-CD2 is an essential component of tip-links in mature auditory hair
      cells. The finding, in the homozygous or compound heterozygous state, of a PCDH15
      frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15-CD2, in profoundly
      deaf children from two unrelated families, extends this conclusion to humans.
      These results provide key information for identification of new components of the
      mature auditory mechano-electrical transduction machinery. This will also serve
      as a basis for the development of gene therapy for deafness caused by PCDH15
      defects.

PMID- 24940004
TI  - A complete series of halocarbonyl molybdenum PNP pincer complexes - Unexpected
      differences between NH and NMe spacers.
AB  - In the present study a complete series of seven-coordinate neutral halocarbonyl
      Mo(II) complexes of the type [Mo(PNPMe-Ph)(CO)2X2] (X = I, Br, Cl, F), featuring
      the new PNP pincer ligand N,N'-bis(diphenylphosphino)-N,N'-methyl-2,6
      diaminopyridine (PNPMe-Ph), were prepared and fully characterized. The synthesis
      of these complexes was accomplished by different methodologies depending on the
      halide ligands. For X = I and Br, [Mo(PNPMe-Ph)(CO)2I2] and [Mo(PNPMe
      Ph)(CO)2Br2] were obtained by reacting [Mo(PNPMe-Ph)(CO)3] with stoichiometric
      amounts of I2 and Br2, respectively. Alternatively, these complexes were obtained
      upon treatment of [MoX2(CO)3(CH3CN)2] (X = I, Br) with 1 equiv. of PNPMe-Ph. On
      the other hand, in the case of X = Cl, [Mo(PNPMe-Ph)(CO)2Cl2] was afforded by the
      reaction of [Mo(CO)4(MU-Cl)Cl]2 with 1 equiv. of PNPMe-Ph. The equivalent
      procedure also worked for X = Br. Finally, addition of 1 equiv. of 1-fluoro-2,4,6
      trimethylpyridinium tetrafluoroborate to [Mo(PNPMe-Ph)(CO)3] yielded the
      analogous fluorine complex [Mo(PNPMe-Ph)(CO)2F2]. The modification of the ligand
      scaffold by introducing a Me group instead of H changed the properties of the PNP
      Ph ligand significantly. While in the present case exclusively neutral seven
      coordinate complexes of the type [Mo(PNPMe-Ph)(CO)2X2] were obtained, with the
      parent PNP-Ph ligand, i.e., featuring NH spacers, cationic seven-coordinate
      complexes of the type [Mo(PNP-Ph)(CO)3X]X were afforded. DFT calculations
      indicated that the reactions are under thermodynamic control. The structures of
      representative complexes were determined by X-ray single crystal analyses.

PMID- 24940006
TI  - BRICS and global health.

PMID- 24940007
TI  - Commodities for better health in Africa--time to invest locally.

PMID- 24940008
TI  - BRICS cooperation in strategic health projects.

PMID- 24940010
TI  - Public health round-up.

PMID- 24940009
TI  - Making fair choices on the path to universal health coverage.

PMID- 24940011
TI  - BRICS seek value for money as health-care costs rise.

PMID- 24940012
TI  - The BRICS countries: a new force in global health?

PMID- 24940013
TI  - Relative health performance in BRICS over the past 20 years: the winners and
      losers.
AB  - OBJECTIVE: To determine whether the health performance of Brazil, the Russian
      Federation, India, China and South Africa--the countries known as BRICS--has kept
      in step with their economic development. METHODS: Reductions in age- and sex
      specific mortality seen in each BRICS country between 1990 and 2011 were
      measured. These results were compared with those of the best-performing countries
      in the world and the best-performing countries with similar income levels. We
      estimated each country's progress in reducing mortality and compared changes in
      that country's mortality rates against other countries with similar mean incomes
      to examine changes in avoidable mortality. FINDINGS: The relative health
      performance of the five study countries differed markedly over the study period.
      Brazil demonstrated fairly even improvement in relative health performance across
      the different age and sex subgroups that we assessed. India's improvement was
      more modest and more varied across the subgroups. South Africa and the Russian
      Federation exhibited large declines in health performance as well as large sex
      specific inequalities in health. Although China's levels of avoidable mortality
      decreased in absolute terms, the level of improvement appeared low in the context
      of China's economic growth. CONCLUSION: When evaluating a country's health
      performance in terms of avoidable mortality, it is useful to compare that
      performance against the performance of other countries. Such comparison allows
      any country-specific improvements to be distinguished from general global
      improvements.

PMID- 24940014
TI  - Socioeconomic inequalities and mortality trends in BRICS, 1990-2010.
AB  - OBJECTIVE: To explore the presence and magnitude of--and change in--socioeconomic
      and health inequalities between and within Brazil, the Russian Federation, India,
      China and South Africa--the countries known as BRICS--between 1990 and 2010.
      METHODS: Comparable data on socioeconomic and health indicators, at both country
      and primary subnational levels, were obtained from publicly available sources.
      Health inequalities between and within countries were identified and summarized
      by using standard gap and gradient metrics. FINDINGS: Four of the BRICS countries
      showed increases in both income level and income inequality between 1990 and
      2010. The exception was Brazil, where income inequality decreased over the same
      period. Between-country inequalities in level of education and access to
      sanitation remained mostly unchanged but the largest between-country difference
      in mean life expectancy increased, from 9 years in 1990 to 20 years in 2010.
      Throughout the study period, there was disproportionality in the burden of
      disease between BRICS. However, the national infant mortality rate fell
      substantially over the study period in all five countries. In Brazil and China,
      the magnitude of subnational income-related inequalities in infant mortality,
      both absolute and relative, also decreased substantially. CONCLUSION: Despite the
      economic prosperity and general improvements in health seen since 1990, profound
      inequalities in health persist both within and between BRICS. However, the
      substantial reductions observed--within Brazil and China--in the inequalities in
      income-related levels of infant mortality are encouraging.

PMID- 24940016
TI  - BRICS: opportunities to improve road safety.
AB  - Brazil, the Russian Federation, India, China and South Africa--the countries
      known as BRICS--are currently undergoing a deep epidemiological transition that
      is mainly driven by rapid economic growth and technological change. The changes
      being observed in the distribution of the burden of diseases and injuries--such
      as recent increases in the incidence of road traffic injuries--are matters of
      concern. BRICS may need stronger institutional capacity to address such changes
      in a timely way. In this paper, we present data on road traffic injuries in BRICS
      and illustrate the enormous challenge that these countries currently face in
      reducing the incidence of such injuries. There is an urgent need to improve road
      safety indicators in every country constituting BRICS. It is imperative for BRICS
      to invest in system-wide road safety interventions and reduce the mortality and
      morbidity from road traffic injuries.

PMID- 24940015
TI  - Time series analysis of the impact of tobacco control policies on smoking
      prevalence among Australian adults, 2001-2011.
AB  - OBJECTIVE: To determine the impact of tobacco control policies and mass media
      campaigns on smoking prevalence in Australian adults. METHODS: Data for
      calculating the average monthly prevalence of smoking between January 2001 and
      June 2011 were obtained via structured interviews of randomly sampled adults aged
      18 years or older from Australia's five largest capital cities (monthly mean
      number of adults interviewed: 2375). The influence on smoking prevalence was
      estimated for increased tobacco taxes; strengthened smoke-free laws; increased
      monthly population exposure to televised tobacco control mass media campaigns and
      pharmaceutical company advertising for nicotine replacement therapy (NRT), using
      gross ratings points; monthly sales of NRT, bupropion and varenicline; and
      introduction of graphic health warnings on cigarette packs. Autoregressive
      integrated moving average (ARIMA) models were used to examine the influence of
      these interventions on smoking prevalence. FINDINGS: The mean smoking prevalence
      for the study period was 19.9% (standard deviation: 2.0%), with a drop from 23.6%
      (in January 2001) to 17.3% (in June 2011). The best-fitting model showed that
      stronger smoke-free laws, tobacco price increases and greater exposure to mass
      media campaigns independently explained 76% of the decrease in smoking prevalence
      from February 2002 to June 2011. CONCLUSION: Increased tobacco taxation, more
      comprehensive smoke-free laws and increased investment in mass media campaigns
      played a substantial role in reducing smoking prevalence among Australian adults
      between 2001 and 2011.

PMID- 24940017
TI  - Progress towards universal health coverage in BRICS: translating economic growth
      into better health.
AB  - Brazil, the Russian Federation, India, China and South Africa--the countries
      known as BRICS--represent some of the world's fastest growing large economies and
      nearly 40% of the world's population. Over the last two decades, BRICS have
      undertaken health-system reforms to make progress towards universal health
      coverage. This paper discusses three key aspects of these reforms: the role of
      government in financing health; the underlying motivation behind the reforms; and
      the value of the lessons learnt for non-BRICS countries. Although national
      governments have played a prominent role in the reforms, private financing
      constitutes a major share of health spending in BRICS. There is a reliance on
      direct expenditures in China and India and a substantial presence of private
      insurance in Brazil and South Africa. The Brazilian health reforms resulted from
      a political movement that made health a constitutional right, whereas those in
      China, India, the Russian Federation and South Africa were an attempt to improve
      the performance of the public system and reduce inequities in access. The move
      towards universal health coverage has been slow. In China and India, the reforms
      have not adequately addressed the issue of out-of-pocket payments. Negotiations
      between national and subnational entities have often been challenging but Brazil
      has been able to achieve good coordination between federal and state entities via
      a constitutional delineation of responsibility. In the Russian Federation, poor
      coordination has led to the fragmented pooling and inefficient use of resources.
      In mixed health systems it is essential to harness both public and private sector
      resources.

PMID- 24940018
TI  - Impact of BRICS' investment in vaccine development on the global vaccine market.
AB  - Brazil, the Russian Federation, India, China and South Africa--the countries
      known as BRICS--have made considerable progress in vaccine production, regulation
      and development over the past 20 years. In 1993, all five countries were
      producing vaccines but the processes used were outdated and non-standardized,
      there was little relevant research and there was negligible international
      recognition of the products. By 2014, all five countries had strong initiatives
      for the development of vaccine technology and had greatly improved their national
      regulatory capacity. South Africa was then the only BRICS country that was not
      completely producing vaccines. South Africa is now in the process of re
      establishing its own vaccine production and passing beyond the stage of simply
      importing, formulating and filling vaccine bulks. Changes in the public sector's
      price per dose of selected vaccines, the global market share represented by
      products from specific manufacturers, and the attractiveness, for multinational
      companies, of partnership and investment opportunities in BRICS companies have
      all been analysed. The results indicate that the BRICS countries have had a major
      impact on vaccine price and availability, with much of that impact attributable
      to the output of Indian vaccine manufacturers. China is expected to have a
      greater impact soon, given the anticipated development of Chinese vaccine
      manufacturers in the near future. BRICS' accomplishments in the field of vaccine
      development are expected to reshape the global vaccine market and accelerate
      access to vaccines in the developing world. The challenge is to turn these
      expectations into strategic actions and practical outcomes.

PMID- 24940020
TI  - BRICS' role in global health and the promotion of universal health coverage: the
      debate continues.

PMID- 24940019
TI  - Progress and challenges of the rural cooperative medical scheme in China.
AB  - PROBLEM: During China's transition to a market economy in the 1980s and 1990s,
      the rural population faced substantial barriers to accessing health care and
      encountered heavier financial burdens than urban residents in paying for
      necessary health services. APPROACH: In 2003, China started to implement a rural
      cooperative medical scheme (RCMS), mainly through government subsidies. The
      scheme operates at the county level and offers a modest benefit package. LOCAL
      SETTING: In spite of rapid economic growth since the early 1980s, income
      disparities in China have increased, particularly between rural and urban
      populations. In response, the government has put greater emphasis on social
      development, including health system development. Examples are the prioritization
      of improved access to health services and the reduction of the burden of payment
      for necessary services. RELEVANT CHANGES: After 10 years of implementation, the
      RCMS now provides coverage to the entire rural population and has substantially
      improved access to health care. Yet despite a drop in out-of-pocket payments as a
      proportion of total health expenditure, paying for necessary services continues
      to cause financial hardship for many rural residents. LESSONS LEARNT: In its
      first decade, the RCMS made progress through political mobilization, government
      subsidies, the readiness of the health-care delivery system, and the availability
      of a monitoring and evaluation system. Further improving the RCMS will require a
      focus on cost containment, quality improvement and making the scheme portable.

PMID- 24940021
TI  - The economic and social benefits of childhood vaccinations in BRICS.

PMID- 24940022
TI  - Tracking the flow of health aid from BRICS countries.

PMID- 24940023
TI  - Tuberculosis in BRICS: challenges and opportunities for leadership within the
      post-2015 agenda.

PMID- 24940024
TI  - BRICS in the response to neglected tropical diseases.

PMID- 24940025
TI  - BRICS' contributions to the global health agenda.

PMID- 24940026
TI  - Coronary arteriovenous fistulae: a review.
AB  - Coronary arteriovenous fistulae are a coronary anomaly, presenting in 0.002% of
      the general population. Their etiology can be congenital or acquired. We present
      a review of recent literature related to their epidemiology, etiology,
      pathophysiology, clinical presentation, diagnostic approach, and therapeutic
      management. 

PMID- 24940027
TI  - Downregulation of Connexin 43 promotes vascular cell loss and excess permeability
      associated with the development of vascular lesions in the diabetic retina.
AB  - PURPOSE: To determine whether downregulation of Connexin 43 (Cx43) expression
      promotes development of acellular capillaries (ACs), pericyte loss (PL), excess
      permeability, and retinal thickening in rat retinas. METHODS: Control rats,
      diabetic rats, and rats intravitreally injected with Cx43 siRNA or scrambled
      siRNA were used in this study to determine if acute downregulation of Cx43
      expression contributes to retinal vascular cell death and excess permeability.
      Western blot (WB) analysis and Cx43 immunostaining were performed to assess Cx43
      protein levels and distribution in the retinal vessels. Concurrently, retinal
      networks were subjected to terminal deoxynucleotidyl transferase-mediated uridine
      5'-triphosphate-biotin nick end labeling (TUNEL) assay and counter-stained to
      assess the number of apoptotic cells, ACs, and PL. Assessment of fluorescein
      isothiocyanate-dextran (FITC-dex) extravasation from retinal capillaries and
      optical coherence tomography (OCT) were performed to determine retinal vascular
      permeability and retinal thickness, respectively. RESULTS: WB analysis indicated
      a significant decrease in the Cx43 protein level in the retinas of the diabetic
      rats and those intravitreally injected with Cx43 siRNA compared to the retinas of
      the control rats. Likewise, the retinal vascular cells of the diabetic rats and
      the Cx43 siRNA-treated rats showed a significant decrease in Cx43 immunostaining.
      Importantly, the number of apoptotic cells, ACs and PL, FITC-dex extravasation,
      and thickness increased in the retinas of the diabetic and Cx43 siRNA-treated
      rats compared to those of the control rats. CONCLUSIONS: Results indicate that
      downregulation of Cx43 expression alone induces vascular cell death and promotes
      vascular permeability in the retina. These findings suggest that diabetes-induced
      downregulation of Cx43 participates in promoting retinal vascular lesions
      associated with diabetic retinopathy (DR).

PMID- 24940028
TI  - Rat retina shows robust circadian expression of clock and clock output genes in
      explant culture.
AB  - PURPOSE: Circadian rhythms are central to vision and retinal physiology. A
      circadian clock located within the retina controls various rhythmic processes
      including melatonin synthesis in photoreceptors. In the present study, we
      evaluated the rhythmic expression of clock genes and clock output genes in
      retinal explants maintained for several days in darkness. METHODS: Retinas were
      dissected from Wistar rats, either wild-type or from the Per1-luciferase
      transgenic line housed under a daily 12 h:12 h light-dark cycle (LD12/12), and
      put in culture at zeitgeber time (ZT) 12 on semipermeable membranes. Explants
      from wild-type rats were collected every 4 h over 3 days, and total RNA was
      extracted, quantified, and reverse transcribed. Gene expression was assessed with
      quantitative PCR, and the periodicity of the relative mRNA amounts was assessed
      with nonlinear least squares fitting to sine wave functions. Bioluminescence in
      explants from Per1-luciferase rats was monitored for several days under three
      different culture protocols. RESULTS: Rhythmic expression was found for all
      studied clock genes and for clock downstream targets such as c-fos and
      arylalkylamine N-acetyltransferase (Aanat) genes. Clock and output genes cycled
      with relatively similar periods and acrophases (peaks of expression during
      subjective night, except c-fos, which peaked around the end of the subjective
      day). Data for Per1 were confirmed with bioluminescence monitoring, which also
      permitted culture conditions to be optimized to study the retina clock.
      CONCLUSIONS: Our work shows the free-running expression profile of multiple clock
      genes and potential clock targets in mammalian retinal explants. This research
      further strengthens the notion that the retina contains a self-sustained
      oscillator that can be functionally characterized in organotypic culture.

PMID- 24940029
TI  - Novel compound heterozygous NMNAT1 variants associated with Leber congenital
      amaurosis.
AB  - PURPOSE: The gene encoding nicotinamide nucleotide adenylyltransferase 1 (NMNAT1)
      was recently found to be mutated in a subset of patients with Leber congenital
      amaurosis (LCA) with macular atrophy. The aim of this study was to determine the
      occurrence and frequency of NMNAT1 mutations and associated phenotypes in
      different types of inherited retinal dystrophies. METHODS: DNA samples of 161
      patients with LCA without genetic diagnosis were analyzed for variants in NMNAT1
      using Sanger sequencing. Variants in exon 5 of NMNAT1, which harbors the majority
      of the previously identified mutations, were screened in 532 additional patients
      with retinal dystrophies. This cohort encompassed 108 persons with isolated or
      autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal
      recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well
      as 104 persons with LCA in whom the causative mutation was previously identified.
      RESULTS: Compound heterozygous alterations were found in six patients with LCA
      and in one person with early-onset RP. All except one carried the common p.E257K
      variant on one allele. Macular atrophy was absent in one patient, who carried
      this variant in combination with a truncating mutation on the other allele. The
      p.E257K alteration was also found in a heterozygous state in five individuals
      with LCA and one with RP while no mutation was detected on the other allele. Two
      individuals with LCA carried other NMNAT1 variants in a heterozygous state,
      whereas no NMNAT1 variants in exon 5 were identified in individuals with CRD. The
      p.E257K variant was found to be enriched in a heterozygous state in individuals
      with LCA (0.94%) compared to Caucasian controls (0.18%), although the difference
      was statistically insignificant (p=0.12). CONCLUSIONS: Although macular atrophy
      can occur in LCA and CRD, no NMNAT1 mutations were found in the latter cohort.
      NMNAT1 variants were also not found in a large group of patients with sporadic or
      autosomal recessive RP. The enrichment of p.E257K in a heterozygous state in
      patients with LCA versus controls suggests that this allele could act as a
      modifier in other genetic subtypes of LCA.

PMID- 24940030
TI  - Pinosylvin-mediated protection against oxidative stress in human retinal pigment
      epithelial cells.
AB  - PURPOSE: In this work, we investigated the ability of pinosylvin (PS), 3,5
      dihydroxy-trans-stilbene, to modulate oxidative stress in human RPE cells. PS, a
      stilbenoid polyphenol, occurs in high concentrations in bark byproducts and
      therefore represents an attractive bioactive compound for health-promoting
      applications. METHODS: First, we evaluated the toxicity range of PS by exposing
      ARPE-19 cells to 0.1-200 uM concentrations of PS for 24 h followed by the cell
      viability test. In the next stage, the ARPE-19 cells were preincubated in PS for
      24 h followed by hydroquinone (HQ) exposure without PS for another 24 h. The cell
      viability test was conducted after HQ exposure. To elucidate the potential
      mechanisms behind PS-mediated protection against oxidative stress, the ARPE-19
      cells were treated with 5 uM PS for 6 h, and mRNA was extracted at four time
      points (2 h, 6 h, 12 h, 24 h) to determine changes in the expression of nuclear
      factor-erythroid 2-related factor-2 (Nrf2), sequestosome 1 (p62/SQSTM1), heme
      oxygenase-1 (HO-1), and glutathione S-transferase pi 1 (GSTP1) genes. To clarify
      the molecular mechanism behind PS-mediated protection further, the ARPE-19 cells
      were transfected with p62 and Nrf2 siRNAs for 24 h, and the roles of p62, Nrf2,
      and its target gene HO-1 in conferring protection against oxidative stress were
      studied with quantitative real-time PCR (qRT-PCR) and the cell viability test.
      RESULTS: PS treatment at concentrations of 5 and 10 uM significantly enhanced
      cell survival from oxidative stress. The expression levels of an enzyme with
      antioxidative, anti-inflammatory, and immunomodulatory properties, HO-1, were
      increased by PS treatment and correlated strongly with cell survival. PS
      treatment did not elevate the expression levels of Nrf2 or its target genes, p62
      or GSTP1, even though it had a clear effect on the expression of HO-1, another
      gene controlled by Nrf2. RNA interference analysis further confirmed the
      important role of Nrf2 and HO-1 in PS-mediated protection against oxidative
      stress whereas the role of p62 seemed to be insignificant at the gene expression
      and cell viability levels. CONCLUSIONS: Our results suggest that PS treatment
      conferred protection against oxidative stress through the induction of HO-1 in
      human RPE cells. Consequently, PS-stilbene compounds, which can be isolated in
      significant amounts from bark waste, may possess health-promoting properties
      against aging-related diseases associated with oxidative stress such as age
      related macular degeneration (AMD) and Alzheimer's disease. These natural
      compounds may offer opportunities for high-value use of bark waste in diverse
      health-related applications.

PMID- 24940031
TI  - Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis
      pigmentosa.
AB  - PURPOSE: Seven genes involved in precursor mRNA (pre-mRNA) splicing have been
      implicated in autosomal dominant retinitis pigmentosa (adRP). We sought to detect
      mutations in all seven genes in Chinese families with RP, to characterize the
      relevant phenotypes, and to evaluate the prevalence of mutations in splicing
      genes in patients with adRP. METHODS: Six unrelated families from our adRP cohort
      (42 families) and two additional families with RP with uncertain inheritance mode
      were clinically characterized in the present study. Targeted sequence capture
      with next-generation massively parallel sequencing (NGS) was performed to screen
      mutations in 189 genes including all seven pre-mRNA splicing genes associated
      with adRP. Variants detected with NGS were filtered with bioinformatics analyses,
      validated with Sanger sequencing, and prioritized with pathogenicity analysis.
      RESULTS: Mutations in pre-mRNA splicing genes were identified in three individual
      families including one novel frameshift mutation in PRPF31 (p.Leu366fs*1) and two
      known mutations in SNRNP200 (p.Arg681His and p.Ser1087Leu). The patients carrying
      SNRNP200 p.R681H showed rapid disease progression, and the family carrying
      p.S1087L presented earlier onset ages and more severe phenotypes compared to
      another previously reported family with p.S1087L. In five other families, we
      identified mutations in other RP-related genes, including RP1 p. Ser781* (novel),
      RP2 p.Gln65* (novel) and p.Ile137del (novel), IMPDH1 p.Asp311Asn (recurrent), and
      RHO p.Pro347Leu (recurrent). CONCLUSIONS: Mutations in splicing genes identified
      in the present and our previous study account for 9.5% in our adRP cohort,
      indicating the important role of pre-mRNA splicing deficiency in the etiology of
      adRP. Mutations in the same splicing gene, or even the same mutation, could
      correlate with different phenotypic severities, complicating the genotype
      phenotype correlation and clinical prognosis.

PMID- 24940034
TI  - Whole exome sequencing identifies a novel splice-site mutation in ADAMTS17 in an
      Indian family with Weill-Marchesani syndrome.
AB  - PURPOSE: Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder,
      characterized by short stature, microspherophakic lens, and stubby hands and feet
      (brachydactyly). WMS is caused by mutations in the FBN1, ADAMTS10, and LTBP2
      genes. Mutations in the LTBP2 and ADAMTS17 genes cause a WMS-like syndrome, in
      which the affected individuals show major features of WMS but do not display
      brachydactyly and joint stiffness. The main purpose of our study was to determine
      the genetic cause of WMS in an Indian family. METHODS: Whole exome sequencing
      (WES) was used to identify the genetic cause of WMS in the family. The
      cosegregation of the mutation was determined with Sanger sequencing. Reverse
      transcription (RT)-PCR analysis was used to assess the effect of a splice-site
      mutation on splicing of the ADAMTS17 transcript. RESULTS: The WES analysis
      identified a homozygous novel splice-site mutation c.873+1G>T in a known WMS-like
      syndrome gene, ADAMTS17, in the family. RT-PCR analysis in the patient showed
      that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the
      ADAMTS17 protein. CONCLUSIONS: The mutation in the WMS-like syndrome gene
      ADAMTS17 also causes WMS in an Indian family. The present study will be helpful
      in genetic diagnosis of this family and increases the number of mutations of this
      gene to six.

PMID- 24940033
TI  - TNF-alpha-induced ICAM-1 expression and monocyte adhesion in human RPE cells is
      mediated in part through autocrine VEGF stimulation.
AB  - PURPOSE: Local inflammation at the RPE cell layer is associated with inflammatory
      cell migration and secretion of proinflammatory cytokines such as tumor necrosis
      factor (TNF)-alpha. TNF-alpha upregulates intercellular adhesion molecule (ICAM)
      1 expression on the RPE, which allows lymphocyte function-associated antigen-1
      (LFA-1) to bind on leukocytes that contribute to leukocyte adhesion at sites of
      inflammation. Vascular endothelial growth factor (VEGF)-A(165)b is generated by
      alternative splicing of VEGF-A in the terminal exon, exon 8. VEGF-A(165)b is
      cytoprotective and antiangiogenic, but its effects on inflammation have not yet
      been elucidated. Therefore, we tested the hypothesis that VEGF-A(165)b regulates
      TNF-alpha-induced ICAM-1 expression and monocyte adhesion in RPE cells. METHODS:
      Primary RPE cells were pretreated with TNF-alpha alone, VEGF-A(165)b alone, VEGF
      A(165)b with anti-VEGF-A(165)b, or the VEGFR-2 inhibitor ZM323881 before exposure
      to TNF-alpha for 24 h. Western blotting and monocyte adhesion assays were
      performed. RESULTS: VEGF-A(165)b and ZM323881 inhibited TNF-alpha-induced
      upregulation of ICAM-1 in RPE cells. The effect of VEGF-A(165)b was neutralized
      by an antibody to VEGF-A(165)b. VEGF-A(165)b ameliorated TNF-alpha-induced
      monocyte-RPE adhesion. CONCLUSIONS: These findings indicate that VEGF-A(165)b
      inhibits TNF-alpha-mediated upregulation of ICAM-1 expression and increases
      monocyte-RPE cell adhesion, suggesting an anti-inflammatory property of VEGF
      A(165)b in the eye.

PMID- 24940035
TI  - Technical brief: Optimized pipeline for isolation of high-quality RNA from
      corneal cell subpopulations.
AB  - PURPOSE: Attempts to determine the transcriptional profile of discrete subsets of
      limbal epithelial cells in situ using laser capture microdissection (LCM) face
      two major challenges. First, the transcriptional profile of cells within a tissue
      may rapidly change as the tissue is excised and exposed to cold ischemia. Second,
      there is a risk of degradation of the RNA as the cellular compartment is
      separated from the remaining tissue. An optimized protocol for LCM of corneal
      epithelium is presented to address these issues. METHODS: Experiments using
      porcine eye globes were carried out to determine both optimal procedures and
      settings for tissue harvest, transport, storage, histology, LCM, and RNA
      isolation. The optimized protocol was validated using human corneal epithelium.
      RESULTS: To facilitate preservation of the gene expression profile, we have
      developed a mechanical tool for dissection of cornea that, in combination with
      flash freezing, enables tissue to be stored within 5 min of enucleation of the
      eye. Furthermore, we describe how RNA from limbal crypt cells may be obtained
      using a procedure involving cryosectioning, histological staining, and LCM.
      CONCLUSION: In this paper, we describe an optimized method for isolating high
      quality RNA from cellular subpopulations confined to the limbal crypts of the
      cornea. The procedure yields RNA in amounts and quality suitable for downstream
      gene expression analyses, such as microarrays or next generation sequencing.

PMID- 24940036
TI  - Endothelial nitric oxide synthase polymorphisms and susceptibility to high
      tension primary open-angle glaucoma in an Egyptian cohort.
AB  - PURPOSE: To analyze the association of polymorphisms of the endothelial nitric
      oxide synthase (NOS3) gene and nitric oxide (NO) levels with high-tension primary
      open-angle glaucoma (POAG) in an Egyptian population. METHODS: This case-control
      study included 160 patients who had high-tension POAG (76 men and 84 women; age
      range 41-75 years) and 110 controls (56 men and 54 women; age range 55-78 years).
      Genotyping of T-786C (rs2070744), Glu298Asp (rs1799983), and the 27-bp
      insertional variable number tandem repeat (VNTR) in intron 4 of the NOS3 gene was
      performed with an amplification refractory mutation system PCR assay. The NO
      level was determined by measuring the total nitrate/nitrite (NOX) plasma level.
      RESULTS: The CC genotype of the T-786C polymorphism was significantly associated
      with POAG (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.26-5.13, p =
      0.007). The C allele was significantly associated with POAG (OR = 1.86, 95% CI =
      1.29-2.69, p<0.001). After stratification by sex, the CC genotype and the C
      allele were significantly associated with POAG in women only (OR = 3.06, 95% CI =
      1.07-8.74, p = 0.03 for the CC genotype, and OR = 2.09, 95% CI = 1.24-3.53, p =
      0.005 for the C allele). The genotype and allele frequencies of Glu298Asp and
      intron 4 were not significant between the patients with POAG and the controls,
      and after stratification by sex. The mean NOX plasma level was significantly
      lower in patients with POAG than in the controls (p = 0.01) and low in the
      (TC+CC) genotype compared to the TT genotype of T-786C in the patients and
      controls (p<0.001). CONCLUSIONS: The results suggest that the CC genotype of T
      786C NOS3 may be associated with an increased risk of developing high-tension
      POAG in Egyptians, particularly women. In addition, decreased NO levels may play
      a role in the development of POAG.

PMID- 24940037
TI  - Novel mutation in FBN1 causes ectopia lentis and varicose great saphenous vein in
      one Chinese autosomal dominant family.
AB  - PURPOSE: To identify genetic defects in a Chinese family with ectopia lentis (EL)
      and varicose great saphenous vein (GSV) and to analyze the correlations between
      phenotype and genotype. METHODS: Twenty-two (12 affected subjects and ten
      unaffected subjects) among 53 members of a Chinese family underwent complete
      physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted
      from the leukocytes in the subjects' peripheral blood. A minimum interval was
      achieved with linkage study and haplotype analysis. All 65 exons and the flanking
      intronic regions of fibrillin-1 (FBN1) were amplified with PCR and screened for
      mutations with direct Sanger sequencing. Molecular modeling was analyzed in an in
      silico study. RESULTS: The linkage study showed a strong cosegregation signal on
      chromosome 15. The non-parametric linkage analysis yielded a maximum score of
      29.1(p<0.00001), and the parametric logarithm of the odds (LOD) score was 3.6.
      The minimum interval of the shared haplotype was rs1565863-rs877228. The best
      candidate gene in this region was FBN1. A novel mutation, c.3928G>A, p.1310G>S in
      exon 31, was identified in FBN1 and cosegregated well in the family. We applied
      molecular modeling to show the effect of this mutation on the fibrillin-1
      structure. The mutation significantly distorts the calcium coordination,
      decreases the binding of the calcium ion in that motif, and affects the local
      calcium-binding epidermal growth factor (cbEGF) interface that depends on Ca
      binding. CONCLUSIONS: FBN1-associated fibrillinopathies are a group of diseases
      with dynamic phenotype changes. Novel mutation p.1310G>S was first reported to
      cause Marfan syndrome (MFS). Our results expand the mutation spectrum in FBN1 and
      enhance our knowledge of genotype-phenotype correlations underlying FBN1
      mutations.

PMID- 24940040
TI  - Determination of xanthine in the presence of hypoxanthine by adsorptive stripping
      voltammetry at the mercury film electrode.
AB  - A stripping method for the determination of xanthine in the presence of
      hypoxanthine at the submicromolar concentration levels is described. The method
      is based on controlled adsorptive accumulation at the thin-film mercury electrode
      followed by a fast linear scan voltammetric measurement of the surface species.
      Optimum experimental conditions were found to be the use of 1.0 * 10(-3) mol L(
      1) NaOH solution as supporting electrolyte, an accumulation potential of 0.00 V
      for xanthine and -0.50 V for hypoxanthine-copper, and a linear scan rate of 200
      mV second(-1). The response of xanthine is linear over the concentration ranges
      of 20-140 ppb. For an accumulation time of 30 minutes, the detection limit was
      found to be 36 ppt (2.3 * 10(-10) mol L(-1)). Adequate conditions for measuring
      the xanthine in the presence of hypoxanthine, copper and other metals, uric acid,
      and other nitrogenated bases were also investigated. The utility of the method is
      demonstrated by the presence of xanthine associated with hypoxanthine, uric acid,
      nitrogenated bases, ATP, and ssDNA. 

PMID- 24940039
TI  - Identification of a novel C-terminal extension mutation in EPHA2 in a family
      affected with congenital cataract.
AB  - PURPOSE: Congenital cataracts occur in 3-4 per 10,000 live births and account for
      5% to 20% of pediatric blindness worldwide. With more than 37 genes known to be
      associated with isolated congenital cataract, whole exome sequencing (WES) was
      recently introduced as an efficient method for screening all known factors.
      METHODS: Whole exome analysis in two members of a four-generation pedigree
      affected with dominant congenital cataract and glaucoma was performed by WES; co
      segregation analysis of identified variants in all pedigree members was completed
      by Sanger sequencing. RESULTS: Analysis of the WES data identified a novel
      pathogenic variant in EPHA2, c.2925dupC, p.(Ile976Hisfs*37), that demonstrated
      complete cosegregation with the phenotype in the pedigree. The mutation occurs in
      the final amino acid before the stop codon of the normal EPHA2 protein and is
      predicted to produce a mutant protein with an erroneous C-terminal extension of
      35 amino acids. Nine other families have been previously reported with dominant
      congenital/juvenile cataracts and mutations in EPHA2. Two additional likely loss
      of-function variants in genes known to cause dominant congenital cataract were
      considered and excluded based on control data and cosegregation analysis: a
      nonsense variant in CYRBB3, c.547G>T, p.(Glu183*), and a splicing variant in
      CRYBA2, c.446+1G>A. CONCLUSIONS: Identification of a novel pathogenic EPHA2
      allele further implicates this gene in congenital cataract. This is only the
      second EPHA2 mutation that specifically affects the most C-terminal PSD95/Dlg/ZO1
      (PDZ)-binding motif and the third pathogenic allele associated with an erroneous
      C-terminal extension beyond the normal stop codon.

PMID- 24940038
TI  - Effects of topically applied tocotrienol on cataractogenesis and lens redox
      status in galactosemic rats.
AB  - PURPOSE: Oxidative and nitrosative stress underlies cataractogenesis, and
      therefore, various antioxidants have been investigated for anticataract
      properties. Several vitamin E analogs have also been studied for anticataract
      effects due to their antioxidant properties; however, the anticataract properties
      of tocotrienols have not been investigated. In this study, we investigated the
      effects of topically applied tocotrienol on the onset and progression of cataract
      and lenticular oxidative and nitrosative stress in galactosemic rats. METHODS: In
      the first part of this study, we investigated the effects of topically applied
      microemulsion formulation of tocotrienol (TTE) using six concentrations ranging
      from 0.01% to 0.2%. Eight groups of Sprague-Dawley rats (n = 9) received
      distilled water, vehicle, or one of the six TTE concentrations as pretreatment
      topically twice daily for 3 weeks while on a normal diet. After pretreatment,
      animals in groups 2-8 received a 25% galactose diet whereas group 1 continued on
      the normal diet for 4 weeks. During this 4-week period, topical treatment
      continued as for pretreatment. Weekly slit-lamp examination was conducted to
      assess cataract progression. At the end of the experimental period, the animals
      were euthanized, and the proteins and oxidative stress parameters were estimated
      in the lenses. In the second part of the study, we compared the anticataract
      efficacy of the TTE with the liposomal formulation of tocotrienol (TTL) using
      five groups of Sprague-Dawley rats (n = 15) that received distilled water, TTE,
      TTL, or corresponding vehicle. The mode of administration and dosing schedule
      were the same as in study 1. Weekly ophthalmic examination and lens protein and
      oxidative stress estimates were performed as in study 1. Lens nitrosative stress
      was also estimated. RESULTS: During the 4-week treatment period, the groups
      treated with 0.03% and 0.02% tocotrienol showed slower progression of cataract
      compared to the vehicle-treated group (p<0.05), whereas the group treated with
      0.2% tocotrienol showed faster progression of cataract compared to the vehicle
      treated group (p<0.05). The lenticular protein content, malondialdehyde,
      superoxide dismutase, and catalase levels were normalized in the groups that
      received 0.03% and 0.02% tocotrienol. The lenticular reduced glutathione also
      showed a trend toward normalization in these groups. In contrast, the group
      treated with 0.2% tocotrienol showed increased lenticular oxidative stress. When
      the microemulsion and liposomal formulations were compared, the effects on
      cataract progression, lens oxidative and nitrosative stress, and lens protein
      content did not show significant differences. CONCLUSIONS: Topically applied
      tocotrienol within the concentration range of less than 0.05% and more than 0.01%
      tends to delay the onset and progression of cataract in galactose-fed rats by
      reducing lenticular oxidative and nitrosative stress. However, topical
      tocotrienol at a concentration of 0.2% and higher aggravates cataractogenesis in
      galactose-fed rats by increasing lens oxidative stress. The anticataract efficacy
      of 0.03% microemulsion of tocotrienol did not differ from its liposomal
      formulations at the same concentration.

PMID- 24940041
TI  - Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a
      critical appraisal.
AB  - Rebamipide was initially developed and approved for use in treating gastric
      ulcers and lesions associated with gastritis. Discovery of its ability to
      increase gastric mucin led to investigations of its effect on ocular surface
      mucin and the subsequent development for use in dry eye patients. Investigations
      have confirmed that rebamipide increases corneal and conjunctival mucin-like
      substances along with improving corneal and conjunctival injury. Clinically,
      rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin
      caused corneal epithelial damage, and can restore the microstructure responsible
      for tear stability. Topical rebamipide has also been shown to be effective in
      treating other ocular surface disorders such as lagophthalmos, lid wiper
      epitheliopathy, and persistent corneal erosion. Rebamipide's ability to modify
      epithelial cell function, improve tear stability, and suppress inflammation in
      the absence of any known major side effects suggest that it may be a beneficial
      first drug of choice for severe dry eye treatment and other ocular surface
      disorders. This review summarizes the history and development of this innovative
      dry eye treatment from its initial use as an effective stomach medication to its
      current use in the treatment of dry eye in Japan. 

PMID- 24940042
TI  - A 6-month, subject-masked, randomized controlled study to assess efficacy of
      dexamethasone as an adjunct to bevacizumab compared with bevacizumab alone in the
      treatment of patients with macular edema due to central or branch retinal vein
      occlusion.
AB  - AIMS: To determine if intravitreal bevacizumab combined with the dexamethasone
      intravitreal implant 0.7 mg improves visual acuity and macular thickness more
      than bevacizumab monotherapy in eyes with macular edema due to branch and central
      retinal vein occlusions. METHODS: Thirty eyes were randomly assigned to receive
      either combination therapy or bevacizumab monotherapy. All patients received
      intravitreal bevacizumab at baseline, followed by dexamethasone implants or sham
      injections 1 week later. Monthly bevacizumab injections were given if the central
      subfield thickness (CST) was >250 MUm, and the combined group received a second
      implant at month 4 or 5 if CST was >250 MUm. RESULTS: At 6 months, several
      secondary endpoints were met. Patients receiving combined therapy required fewer
      bevacizumab reinjections compared to those receiving monotherapy (two versus
      three; P=0.02), experienced greater mean reductions in CST from randomization (
      56 MUm versus +45 MUm; P=0.01), and were more likely to have resolved all edema
      (CST <250 MUm) (7/11 versus 2/14; P=0.02). The primary endpoint was not met since
      mean visual acuity changes from baseline were similar in the two groups (P=0.75).
      CONCLUSION: In patients with macular edema due to vein occlusions, bevacizumab
      with dexamethasone implants produces greater improvements in macular thickness
      compared to bevacizumab monotherapy, despite fewer bevacizumab injections.

PMID- 24940043
TI  - Diffuse lamellar keratitis in the femtosecond-assisted LASIK flap tunnel.
AB  - Here we report a case of a 29-year-old myopic female who underwent femtosecond
      laser-assisted in situ keratomileusis (LASIK) and, on the first postoperative day
      slit-lamp examination revealed a dense, white, granular reaction with the
      presence of some blood droplets (stage I diffuse lamellar keratitis [DLK]) in her
      left eye, specifically localized into the femtosecond LASIK flap tunnel (not
      extended to the flap interface). The patient received intensive treatment with
      topical corticosteroids and 5 days later the granular reaction had completely
      resolved. A new site of DLK, ie, the flap tunnel, in femtosecond-assisted LASIK
      is presented. DLK into the flap tunnel could be managed with corticosteroids if
      detected early, without affecting the flap interface. 

PMID- 24940044
TI  - Ineffectiveness of intrastromal voriconazole for filamentous fungal keratitis.
AB  - PURPOSE: The purpose of this study is to describe the ineffectiveness of
      intrastromal voriconazole injection for filamentous fungal keratitis by
      contrasting the effectiveness for yeast keratitis. METHODS: We examined seven
      fungal keratitis patients prospectively. All yeast was identified by molecular
      phylogenetic analyses of the chromosomal regions coding for the D1/D2 domain of
      the large-subunit 26S ribosomal RNA gene. All filamentous fungi were identified
      by the sequencing of internal transcribed spacers of the ribosomal DNA gene
      regions. Approximately 0.1 mL of voriconazole diluted with saline to 1.0% was
      injected with a 30-gauge needle inserted obliquely into the three to five clear
      cornea sites around the abscess. All subjects were administered natamycin
      ointment and oral itraconazole. When needed, intravenous micafungin,
      voriconazole, and/or intracameral voriconazole were added. Clinical courses were
      observed by the slit lamp microscope. Histopathology was examined when the
      corneas were removed. RESULTS: All cases that were caused by yeast healed quickly
      after injections. Two cases of keratitis caused by Fusarium, and one case caused
      by Aspergillus, did not heal completely. In the Fusarium cases, additional
      antifungal medications (3.0% topical voriconazole and intravenous injection of
      micafungin) were needed. After optical penetrating keratoplasty in one of the
      cases, fungi were found in the deep stroma of the removed cornea. In the case of
      Aspergillus keratitis, pathological findings also showed fungi deep in the stroma
      of the removed cornea and the keratitis recurred after therapeutic penetrating
      keratoplasty. CONCLUSION: Intrastromal voriconazole injection is successful in
      treating yeast keratitis. However this is not the case for filamentous fungal
      keratitis.

PMID- 24940045
TI  - Evaluation of patients with diffuse unilateral subacute neuroretinitis by
      spectral domain optical coherence tomography with enhanced depth imaging.
AB  - BACKGROUND: The purpose of this study was to determine the value of spectral
      domain optical coherence tomography (SD-OCT) in assessing patients with diffuse
      unilateral subacute neuroretinitis (DUSN). METHODS: This was an observational
      case series with clinical imaging correlation performed at the Retina and
      Vitreous Institute of Londrina and State University of Londrina, Parana, Brazil.
      The series comprised ten consecutive patients with a confirmed diagnosis of DUSN,
      ie, seven patients with late-stage disease and three with early-stage disease,
      who were assessed by SD-OCT for mean macular, retinal nerve fiber layer, and
      choroidal thickness using enhanced depth imaging software. RESULTS: Comparing the
      affected eye with the healthy fellow eye, significant diffuse atrophy of the
      retinal layers with a decrease in mean macular (P=0.004) and retinal nerve fiber
      layer (P=0.002) thickness was found in all cases. There was no difference in
      choroidal thickness (P=0.262). CONCLUSION: The correlation of SD-OCT results with
      central vision and funduscopic findings may explain the profound loss of visual
      function in patients with DUSN.

PMID- 24940048
TI  - Single-arm, observational study of the ease of use of a redesigned pen device to
      deliver recombinant human follicle-stimulating hormone (follitropin alfa) for
      assisted reproductive technology treatment.
AB  - PURPOSE: Evaluation of patients' ease of use of the redesigned, disposable, ready
      to-use follitropin alfa pen during controlled ovarian stimulation for assisted
      reproductive technology. METHODS: This single-center, observational, open-label,
      single-arm study recruited infertile normo-ovulatory women (aged 18-45 years).
      Nurses trained patients to self-administer recombinant human follicle-stimulating
      hormone daily using the follitropin alfa pen (300 IU, 450 IU, and 900 IU). Before
      treatment, patients completed Questionnaire A. Following self-administered
      treatment, on stimulation days 5-6 and 7-8 (within a day of receiving recombinant
      human chorionic gonadotropin), patients completed Questionnaire B. Nurses
      completed an ease-of-learning/teaching questionnaire. The primary endpoint was
      proportion of patients rating the pen as "easy/very easy" to use (Questionnaire
      B) on the final visit before recombinant human chorionic gonadotropin. Secondary
      endpoints included: proportion of patients rating the follitropin alfa pen as
      easy to learn, use, prepare, deliver, and dispose of (Questionnaires A and B).
      Proportions (95% confidence intervals [CIs]) were provided for primary and
      secondary endpoints. Adverse events were reported descriptively. RESULTS: Eighty
      six patients received recombinant human follicle-stimulating hormone. Of the 72
      patients who had completed the overall assessment questions, 66 (91.7%; 95% CI
      =82.7%-96.9%) found the pen "easy" to use. Also, 70/86 (81.4%) patients "strongly
      agreed/agreed" that, overall, it was easy to learn how to use the pen; 72/86
      (83.7%) "strongly agreed/agreed" that easily understandable, verbal information
      was provided; and 70/86 (81.4%) were confident about using the pen correctly. In
      total, 24/26 nurses (92.3%; 95% CI =74.9%-99.1%) rated the pen as easy to use.
      Clinical pregnancy rate/patient/cycle/embryo transfer was 37%. Twenty-six ovarian
      hyperstimulation syndrome events were reported (none severe; 16 patients [19%]);
      of these, 13 occurred at embryo transfer. CONCLUSION: In this observational
      study, patients had a high acceptance of the redesigned follitropin alfa pen,
      with most finding it very easy/easy to use. Assisted reproductive technology
      nurses found the pen very easy/easy to teach.

PMID- 24940046
TI  - GLP-1(28-36)amide, the Glucagon-like peptide-1 metabolite: friend, foe, or
      pharmacological folly?
AB  - The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic
      target for the treatment of type 2 diabetes. GLP-1 mediates its key
      insulinotropic effects via a G-protein coupled receptor expressed on beta-cells
      and other pancreatic cell types. The insulinotropic activity of GLP-1 is
      terminated via enzymatic cleavage by dipeptidyl peptidase-4. Until recently, GLP
      1-derived metabolites were generally considered metabolically inactive; however,
      accumulating evidence indicates some have biological activity that may contribute
      to the pleiotropic effects of GLP-1 independent of the GLP-1 receptor. Recent
      reports describing the putative effects of one such metabolite, the GLP-1-derived
      nonapeptide GLP-1(28-36) amide, are the focus of this review. Administration of
      the nonapeptide elevates cyclic adenosine monophosphate (cAMP) and activates
      protein kinase A, beta-catenin, and cAMP response-element binding protein in
      pancreatic beta-cells and hepatocytes. In stressed cells, the nonapeptide targets
      the mitochondria and, via poorly defined mechanisms, helps to maintain
      mitochondrial membrane potential and cellular adenosine triphosphate levels and
      to reduce cytotoxicity and apoptosis. In mouse models of diet-induced obesity,
      treatment with the nonapeptide reduces weight gain and ameliorates associated
      pathophysiology, including hyperglycemia, hyperinsulinemia, and hepatic
      steatosis. Nonapeptide administration in a streptozotocin-induced model of type 1
      diabetes also improves glucose disposal concomitant with elevated insulin levels
      and increased beta-cell mass and proliferation. Collectively, these results
      suggest some of the beneficial effects of GLP-1 receptor analogs may be mediated
      by the nonapeptide. However, the concentrations required to elicit some of these
      effects are in the micromolar range, leading to reservations about potentially
      related therapeutic benefits. Moreover, although controversial, concerns have
      been raised about the potential for incretin-based therapies to promote
      pancreatitis and pancreatic and thyroid cancers. The effects ascribed to the
      nonapeptide make it a potential contributor to such outcomes, raising additional
      questions about its therapeutic suitability. Notwithstanding, the nonapeptide,
      like other GLP-1 metabolites, appears to be biologically active. Increasing
      understanding of such noncanonical GLP-1 activities should help to improve future
      incretin-based therapeutics. 

PMID- 24940049
TI  - Developing a bone mineral density test result letter to send to patients: a mixed
      methods study.
AB  - PURPOSE: To use a mixed-methods approach to develop a letter that can be used to
      notify patients of their bone mineral density (BMD) results by mail that may
      activate patients in their bone-related health care. PATIENTS AND METHODS: A
      multidisciplinary team developed three versions of a letter for reporting BMD
      results to patients. Trained interviewers presented these letters in a random
      order to a convenience sample of adults, aged 50 years and older, at two
      different health care systems. We conducted structured interviews to examine the
      respondents' preferences and comprehension among the various letters. RESULTS: A
      total of 142 participants completed the interview. A majority of the participants
      were female (64.1%) and white (76.1%). A plurality of the participants identified
      a specific version of the three letters as both their preferred version (45.2%;
      P<0.001) and as the easiest to understand (44.6%; P<0.01). A majority of
      participants preferred that the letters include specific next steps for improving
      their bone health. CONCLUSION: Using a mixed-methods approach, we were able to
      develop and optimize a printed letter for communicating a complex test result
      (BMD) to patients. Our results may offer guidance to clinicians, administrators,
      and researchers who are looking for guidance on how to communicate complex health
      information to patients in writing.

PMID- 24940047
TI  - Ivabradine, coronary artery disease, and heart failure: beyond rhythm control.
AB  - Elevated heart rate could negatively influence cardiovascular risk in the general
      population. It can induce and promote the atherosclerotic process by means of
      several mechanisms involving endothelial shear stress and biochemical activities.
      Furthermore, elevated heart rate can directly increase heart ischemic conditions
      because of its skill in unbalancing demand/supply of oxygen and decreasing the
      diastolic period. Thus, many pharmacological treatments have been proposed in
      order to reduce heart rate and ameliorate the cardiovascular risk profile of
      individuals, especially those suffering from coronary artery diseases (CAD) and
      chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive
      drug approved and currently used in humans, created in order to selectively
      reduce sinus node function and to overcome the many side effects of similar
      pharmacological tools (ie, beta-blockers or calcium channel antagonists). The aim
      of our review is to evaluate the role and the safety of this molecule on CAD and
      CHF therapeutic strategies. 

PMID- 24940050
TI  - High-throughput Methods Redefine the Rumen Microbiome and Its Relationship with
      Nutrition and Metabolism.
AB  - Diversity in the forestomach microbiome is one of the key features of ruminant
      animals. The diverse microbial community adapts to a wide array of dietary
      feedstuffs and management strategies. Understanding rumen microbiome composition,
      adaptation, and function has global implications ranging from climatology to
      applied animal production. Classical knowledge of rumen microbiology was based on
      anaerobic, culture-dependent methods. Next-generation sequencing and other
      molecular techniques have uncovered novel features of the rumen microbiome. For
      instance, pyrosequencing of the 16S ribosomal RNA gene has revealed the taxonomic
      identity of bacteria and archaea to the genus level, and when complemented with
      barcoding adds multiple samples to a single run. Whole genome shotgun sequencing
      generates true metagenomic sequences to predict the functional capability of a
      microbiome, and can also be used to construct genomes of isolated organisms.
      Integration of high-throughput data describing the rumen microbiome with classic
      fermentation and animal performance parameters has produced meaningful advances
      and opened additional areas for study. In this review, we highlight recent
      studies of the rumen microbiome in the context of cattle production focusing on
      nutrition, rumen development, animal efficiency, and microbial function. 

PMID- 24940051
TI  - Cognitive and affective assessment in day care versus institutionalized elderly
      patients: a 1-year longitudinal study.
AB  - PURPOSE: Cognitive decline and depression are two common mental health problems
      that may create a need for long-term care among the elderly. In the last decade,
      the percentage of older adults who receive health care in nursing homes, day care
      centers, or home support services has increased in Europe. The objectives of this
      descriptive and nonrandomized longitudinal study were to evaluate and to compare
      the cognitive and affective evolution of day care versus institutionalized older
      patients through a 1-year period, and to assess the presence of cognitive and
      affective impairment as a function of the care setting. PATIENTS AND METHODS:
      Ninety-four patients were assessed at baseline, and 63 (67.0%) were reassessed 1
      year later. Neuropsychological assessment included measures of cognitive
      performance (general cognitive status, visuospatial, and language abilities) and
      affective status (depressive symptoms). RESULTS: Our findings indicated that the
      majority of the participants (day care and institutionalized patients) had mild
      moderate cognitive impairment at baseline, which significantly increased in both
      groups after 1-year follow-up. However, the rate of change in global cognitive
      function did not significantly differ between groups over time. Regarding
      language abilities, naming function maintained among day care patients in
      comparison with institutionalized patients, who showed worse performance at
      follow-up. As regards to affective status, results revealed that
      institutionalized patients had a significant reduction in depressive symptoms at
      follow-up, when compared to day care patients. Results also highlight the high
      frequency of cognitive impairment and depressive symptoms regardless of the care
      setting. CONCLUSION: Our findings revealed a similar global cognitive decline
      rate between patients receiving day care services and those residing in a nursing
      home at the 1-year follow-up, and slightly different trajectories in other
      outcomes such as naming function and depressive symptoms.

PMID- 24940052
TI  - Short-term efficacy of calcium fructoborate on subjects with knee discomfort: a
      comparative, double-blind, placebo-controlled clinical study.
AB  - Calcium fructoborate (CFB) at a dose of 110 mg twice per day was previously
      reported to improve knee discomfort during the first 14 days of treatment. In
      this study, 60 participants with self-reported knee discomfort were randomized
      into two groups receiving CFB or placebo. Initial levels of knee discomfort were
      evaluated by Western Ontario and McMaster Universities Arthritis Index (WOMAC)
      and McGill Pain Questionnaire (MPQ) scores at the beginning of the study and also
      at 7 and 14 days after treatment. Results showed that supplementation with CFB
      significantly improved knee discomfort in the study subjects; significant
      reductions of mean within-subject change in WOMAC and MPQ scores were observed
      for the CFB group compared to the placebo group at both 7 and 14 days after
      treatment. Estimated treatment differences for the MPQ score were -5.8 (P=0.0009)
      and -8.9 (P<0.0001) at Day 7 and 14, respectively. Estimated differences for the
      WOMAC score were -5.3 (P=0.06) and -13.73 (P<0.0001) at Day 7 and 14,
      respectively. Negative values indicate greater reductions in reported discomfort.
      On both Day 7 and Day 14, the trend was toward greater improvement in the CFB
      group. The placebo group did not exhibit any change in the WOMAC and MPQ scores.
      In conclusion, supplementation with 110 mg CFB twice per day was associated with
      improving knee discomfort during the 2 weeks of intake. 

PMID- 24940053
TI  - Outcomes and costs of treating chronic obstructive pulmonary disease with inhaled
      fixed combinations: the Italian perspective of the PATHOS study.
AB  - PURPOSE: Fixed-dose combinations of inhaled corticosteroids and long-acting beta2
      agonists have proven to prevent and reduce chronic obstructive pulmonary disease
      (COPD) exacerbations. The aim of this analysis was to explore the clinical
      consequences and direct health care costs of applying the findings of the PATHOS
      (An Investigation of the Past 10 Years Health Care for Primary Care Patients with
      Chronic Obstructive Pulmonary Disease) study to the Italian context. PATIENTS AND
      METHODS: Effectiveness data from the PATHOS study, a population-based,
      retrospective, observational registry study conducted in Sweden, in terms of
      reduction in COPD and pneumonia-related hospitalizations, were considered, in
      order to estimate the differences in resource consumption between patients
      treated with budesonide/formoterol and fluticasone/salmeterol. The base case
      considers the average dosages of the two drugs reported in the PATHOS study and
      the actual public price in charges to the Italian National Health Service, while
      the difference in hospitalization rates reported in the PATHOS study was costed
      based on Italian real-world data. RESULTS: The PATHOS study demonstrated a
      significant reduction in COPD hospitalizations and pneumonia-related
      hospitalizations in patients treated with budesonide/formoterol versus
      fluticasone/salmeterol (-29.1% and -42%, respectively). In the base case, the
      treatment of a patient for 1 year with budesonide/formoterol led to a saving of
      ?499.90 (?195.10 for drugs, ?193.10 for COPD hospitalizations, and ?111.70 for
      pneumonia hospitalizations) corresponding to a -27.6% difference compared with
      fluticasone/salmeterol treatment. CONCLUSION: Treatment of COPD with
      budesonide/formoterol compared with fluticasone/salmeterol could lead to a
      reduction in direct health care costs, with relevant improvement in clinical
      outcomes.

PMID- 24940055
TI  - Ventilatory requirements of quadriceps resistance training in people with COPD
      and healthy controls.
AB  - BACKGROUND: It is proposed that resistance training (RT) does not activate the
      cardiopulmonary system to the same extent as whole-body exercise. This is
      important for patients with chronic obstructive pulmonary disease (COPD) who are
      ventilatory limited. OBJECTIVE: The aim was to assess the ventilatory response to
      an isokinetic quadriceps RT program in people with COPD and healthy controls.
      DESIGN: Observational. REGISTRATION NUMBER: ISRCTN22764439. SETTING: Outpatient,
      university teaching hospital. PARTICIPANTS AND OUTCOME MEASURES: People with COPD
      (n=14) and healthy controls (n=11) underwent breath-by-breath analysis of their
      ventilation during an RT session (five sets of 30 maximal knee extensions at 180
      degrees /sec). Subjects performed a maximal cycle ergometry test (CET) at
      baseline. Peak ventilation (VE; L/min) and oxygen consumption (VO2; mL/kg/min)
      were collected. The same system measured VO2 and VE during the RT session.
      Parameters are presented as a percentage of the maximal CET. Isokinetic workload,
      symptom scores, heart rate (HR), and oxygen saturation were documented post
      training. RESULTS: People with COPD worked at higher percentages of their maximal
      capacity than controls (mean range between sets 1-5 for VO2 =49.1%-60.1% [COPD],
      45.7%-51.43% [controls] and for VE =57.6%-72.2% [COPD], 49.8%-63.6% [controls]),
      although this was not statistically significant (P>0.1 in all cases). In absolute
      terms, the difference between groups was only significant for actual VO2 on set 2
      (P<0.05). Controls performed more isokinetic work than patients with COPD
      (P<0.05). Median Borg symptom scores after RT were the same in both groups (3
      breathlessness, 13 exertion), no de-saturation occurred, and both groups were
      training at >=65% of their maximum HR. CONCLUSION: No statistically significant
      differences were found between people with COPD and healthy controls for VO2 and
      VE achieved during training. The symptoms associated with training were within
      acceptable limits.

PMID- 24940056
TI  - Magnesium ion implantation on a micro/nanostructured titanium surface promotes
      its bioactivity and osteogenic differentiation function.
AB  - As one of the important ions associated with bone osseointegration, magnesium was
      incorporated into a micro/nanostructured titanium surface using a magnesium
      plasma immersion ion-implantation method. Hierarchical hybrid
      micro/nanostructured titanium surfaces followed by magnesium ion implantation for
      30 minutes (Mg30) and hierarchical hybrid micro/nanostructured titanium surfaces
      followed by magnesium ion implantation for 60 minutes (Mg60) were used as test
      groups. The surface morphology, chemical properties, and amount of magnesium ions
      released were evaluated by field-emission scanning electron microscopy, energy
      dispersive X-ray spectroscopy, field-emission transmission electron microscopy,
      and inductively coupled plasma-optical emission spectrometry. Rat bone marrow
      mesenchymal stem cells (rBMMSCs) were used to evaluate cell responses, including
      proliferation, spreading, and osteogenic differentiation on the surface of the
      material or in their medium extraction. Greater increases in the spreading and
      proliferation ability of rBMMSCs were observed on the surfaces of magnesium
      implanted micro/nanostructures compared with the control plates. Furthermore, the
      osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) genes were
      upregulated on both surfaces and in their medium extractions. The enhanced cell
      responses were correlated with increasing concentrations of magnesium ions,
      indicating that the osteoblastic differentiation of rBMMSCs was stimulated
      through the magnesium ion function. The magnesium ion-implanted
      micro/nanostructured titanium surfaces could enhance the proliferation,
      spreading, and osteogenic differentiation activity of rBMMSCs, suggesting they
      have potential application in improving bone-titanium integration. 

PMID- 24940054
TI  - Activity restriction in mild COPD: a challenging clinical problem.
AB  - Dyspnea, exercise intolerance, and activity restriction are already apparent in
      mild chronic obstructive pulmonary disease (COPD). However, patients may not seek
      medical help until their symptoms become troublesome and persistent and
      significant respiratory impairment is already present; as a consequence, further
      sustained physical inactivity may contribute to disease progression. Ventilatory
      and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction
      are present to a variable degree in patients with mild COPD, and collectively may
      contribute to exercise intolerance. As such, there is increasing interest in
      evaluating exercise tolerance and physical activity in symptomatic patients with
      COPD who have mild airway obstruction, as defined by spirometry. Simple
      questionnaires, eg, the modified British Medical Research Council dyspnea scale
      and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental
      and endurance exercise tests can be used to assess exercise performance and
      functional status. Pedometers and accelerometers are used to evaluate physical
      activity, and endurance tests (cycle or treadmill) using constant work rate
      protocols are used to assess the effects of interventions such as pulmonary
      rehabilitation. In addition, alternative outcome measurements, such as tests of
      small airway dysfunction and laboratory-based exercise tests, are used to measure
      the extent of physiological impairment in individuals with persistent dyspnea.
      This review describes the mechanisms of exercise limitation in patients with mild
      COPD and the interventions that can potentially improve exercise tolerance. Also
      discussed are the benefits of pulmonary rehabilitation and the potential role of
      pharmacologic treatment in symptomatic patients with mild COPD. 

PMID- 24940057
TI  - Liver cancer cells: targeting and prolonged-release drug carriers consisting of
      mesoporous silica nanoparticles and alginate microspheres.
AB  - A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs)
      and organic alginate (denoted as MSN@Alg) was successfully synthesized by air
      dynamic atomization and applied to the intracellular drug delivery systems (DDS)
      of liver cancer cells with sustained release and specific targeting properties.
      MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides
      a large surface area for high drug loading and alginate provides excellent
      biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was
      used as a model drug, and the sustained release behavior of the rhodamine 6G
      loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting
      therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres,
      and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was
      functionalized onto the surface of MSN@Alg for targeting liver cancer cells,
      hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]
      2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning
      microscopy indicate that the MSN@Alg microspheres were successfully uptaken by
      HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery
      efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic
      acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with
      the non-RGD case. The synthesized MSN@Alg microspheres show great potential as
      drug vehicles with high biocompatibility, sustained release, and targeting
      features for future intracellular DDS. 

PMID- 24940058
TI  - Poly(styrene)-b-poly(DL-lactide) copolymer-based nanoparticles for anticancer
      drug delivery.
AB  - Poly(styrene)-b-poly(DL-lactide) (PS-PDLLA) copolymer-based nanoparticles (NPs)
      of a narrow size distribution, negative zeta potential, and spherical shape were
      fabricated for the delivery of docetaxel (DCT). The particle size was
      consistently maintained in serum for 24 hours and a sustained drug release
      pattern was observed for 10 days in the tested formulations. The cytotoxicity of
      the developed blank NPs was negligible in prostate cancer (PC-3) cells. Cellular
      uptake and distribution of the constructed NPs containing a hydrophobic
      fluorescent dye was monitored by confocal laser scanning microscopy (CLSM) for 24
      hours. Anti-tumor efficacy of the PS-PDLLA/DCT NPs in PC-3 cells was
      significantly more potent than that of the group treated with commercially
      available DCT, Taxotere (P<0.05). Blood biochemistry tests showed that no serious
      toxicity was observed with the blank NPs in the liver and kidney. In a
      pharmacokinetic study of DCT in rats, in vivo clearance of PS-PDLLA/DCT NPs
      decreased while the half-life in blood increased compared to the Taxotere-treated
      group (P<0.05). The PS-PDLLA NPs are expected to be a biocompatible and efficient
      nano-delivery system for anticancer drugs.

PMID- 24940060
TI  - Enhanced cellular uptake of maleimide-modified liposomes via thiol-mediated
      transport.
AB  - With a small amount of maleimide modification on the liposome surface, enhanced
      cellular uptake of liposomes and drug-delivery efficiency can be obtained both in
      vitro and in vivo. Herein, we describe the mechanisms underlying this enhanced
      cellular uptake. Suppression of the cellular uptake of maleimide-modified
      liposomes (M-GGLG, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate
      [GGLG]/cholesterol/poly(ethylene glycol) - 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine [PEG5000-DSPE]/maleimide [M]-PEG5000-Glu2C18 at a molar ratio
      of 5:5:0.03:0.03) caused by temperature block and addition of serum was
      alleviated compared with that of liposomes without maleimide modification (GGLG
      liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar
      ratio of 5:5:0.03:0.03). When 0.01 nM N-ethylmaleimide was used to pre-block
      cellular thiols, the cellular uptake of M-GGLG liposomes was decreased to
      approximately 70% in HeLa, HCC1954, MDA-MB-468, and COS-7 cell lines. Moreover,
      inhibition of a thiol-related reductase such as protein disulfide isomerase
      resulted in a 15%-45% inhibition of the cellular uptake of M-GGLG liposomes,
      whereas GGLG liposomes were not influenced. Further, single and mixed inhibitors
      of clathrin-mediated endocytosis, caveolae-mediated endocytosis, and
      macropinocytosis did not efficiently inhibit the cellular uptake of M-GGLG
      liposomes. Using confocal microscopy, we verified that M-GGLG liposomes were
      localized partially in lysosomes after inhibition of the mentioned conventional
      endocytic pathways. Therefore, it was hypothesized that the mechanisms underlying
      the enhanced cellular uptake of liposomes by maleimide modification was thiol
      mediated membrane trafficking, including endocytosis and energy-independent
      transport.

PMID- 24940059
TI  - Surface modifications of silica nanoparticles are crucial for their inert versus
      proinflammatory and immunomodulatory properties.
AB  - BACKGROUND: Silica (SiO2) nanoparticles (NPs) are widely used in diverse
      industrial and biomedical applications. Their applicability depends on surface
      modifications, which can limit potential health problems. OBJECTIVE: To assess
      the potential impact of SiO2 NP exposure and NPs chemical modifications in
      allergic airway inflammation. METHODS: Mice were sensitized by five repetitive
      intraperitoneal injections of ovalbumin/aluminum hydroxide (1 MUg) over 42 days,
      then intratracheally instilled with plain or modified SiO2 NPs (50 MUg/mouse),
      and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days
      later, allergic inflammation was evaluated by cell differentiation of
      bronchoalveolar lavage fluid, lung function and gene expression and
      histopathology, as well as electron and confocal microscopy of pulmonary tissue.
      RESULTS: Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in
      vivo, highlighted by enhanced infiltration of inflammatory cells in the
      bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2)
      cytokine pattern, differentiation of type 2 macrophages, and by morphological
      changes in the lung of sensitized mice. These effects were dramatically
      attenuated using surface-functionalized NPs with amino and phosphate groups, but
      not with polyethylene glycol. The role of macrophages in taking up SiO2 NPs was
      confirmed by flow cytometry, confocal microscopy, and gene expression analysis.
      CONCLUSION: Our data suggest that amino and phosphate surface modifications, but
      not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory
      effect of SiO2 NPs in allergic airway inflammation, paving the way for new
      strategies in the production of nanomaterials with lower health impact for
      humans.

PMID- 24940061
TI  - Effect of calligraphy training on hyperarousal symptoms for childhood survivors
      of the 2008 China earthquakes.
AB  - BACKGROUND: This study investigated the treatment effects of calligraphy therapy
      on childhood survivors of the 2008 Sichuan earthquakes in the People's Republic
      of China. METHODS: In experiment 1, 129 children participated in a 30-day
      calligraphic training, and 81 children were controls. The Children's Revised
      Impact of Event Scale was adopted to assess behavioral effects. Experiment 2
      involved 41 treatment subjects and 39 controls, with the same procedure as in
      experiment 1 except that salivary cortisol level was also measured as a
      physiological indicator. RESULTS: After 30 days of calligraphy treatment, the
      arousal symptoms and salivary cortisol levels in the experimental group decreased
      from 5.72+/-0.31 and 13.34+/-2.88 to 4.98+/-0.31 and 9.99+/-2.81, respectively.
      In the control group, there was not a significant decrease from pretest to post
      test. In addition, the arousal scores in posttest (4.98+/-4.39) were
      significantly lower than midtest (5.71+/-4.14) for girls; in contrast, for boys,
      posttest (4.90+/-4.24) showed little change compared with midtest (5.04+/-4.36),
      but both were significantly lower than pretest (6.42+/-4.59). CONCLUSIONS:
      Calligraphy therapy was effective in reducing hyperarousal symptoms among child
      survivors.

PMID- 24940062
TI  - Determining a diagnostic cut-off on the Teate Depression Inventory.
AB  - A small but growing body of literature suggests that the Teate Depression
      Inventory (TDI) may be an "objective" measure of depression compared with other
      commonly used scales. Furthermore, the TDI has strong psychometric properties in
      both clinical and nonclinical samples. The present study aimed to extend the use
      of TDI by identifying cut-off scores that could differentiate varying levels of
      depression severity in a group of clinically diagnosed depression disorder
      patients (N=125). Three receiver operating characteristic curve analyses
      indicated cut-off scores of 21 (sensitivity =0.86, specificity =0.94, and
      classification accuracy =0.90); 36 (sensitivity =0.84, specificity =0.96, and
      classification accuracy =0.92); and 50 (sensitivity =0.81, specificity =0.93, and
      classification accuracy =0.90), for minimal, mild, moderate, and severe
      depression, respectively. Results suggest that the TDI measures depression
      severity across a broad range with high test accuracy and may be appropriately
      used to screen for depression. 

PMID- 24940064
TI  - Perceiving "ghost" images: a unique case of visual allesthesia with hemianopsia
      in mitochondrial disease.
AB  - A 49-year-old man with mitochondrial disease presented with visual allesthesia, a
      rare and puzzling phenomenon. He was admitted for treatment because of
      convulsions. After the convulsions ceased, he exhibited left homonymous
      hemianopsia. Brain diffusion-weighted magnetic resonance imaging (MRI) showed a
      high-intensity area in the right occipital lobe. Both the hemianopsia and the MRI
      activation in this area disappeared by day 36 of hospitalization. On the morning
      of day 57, right homonymous hemianopsia emerged in a singular manner. The patient
      perceived an illusory object (a bottle placed by the bedside) in his left visual
      field, while the real object was in his blind right field. This case of visual
      allesthesia was accompanied by palinopsia, ie, perseveration of the image of the
      bottle. Diffusion-weighted MRI showed a new, high-intensity area in the left
      occipital lobe. We believe the visual allesthesia resulted from transfer of
      cortical information obtained by blindsight between hemispheres as a result of
      epileptic excitation. 

PMID- 24940066
TI  - Effectiveness of pharmacist dosing adjustment for critically ill patients
      receiving continuous renal replacement therapy: a comparative study.
AB  - BACKGROUND: The impact of continuous renal replacement therapy (CRRT) on drug
      removal is complicated; pharmacist dosing adjustment for these patients may be
      advantageous. This study aims to describe the development and implementation of
      pharmacist dosing adjustment for critically ill patients receiving CRRT and to
      examine the effectiveness of pharmacist interventions. METHODS: A comparative
      study was conducted in an intensive care unit (ICU) of a university-affiliated
      hospital. Patients receiving CRRT in the intervention group received specialized
      pharmacy dosing service from pharmacists, whereas patients in the no-intervention
      group received routine medical care without pharmacist involvement. The two
      phases were compared to evaluate the outcome of pharmacist dosing adjustment.
      RESULTS: The pharmacist carried out 233 dosing adjustment recommendations for
      patients receiving CRRT, and 212 (90.98%) of the recommendations were well
      accepted by the physicians. Changes in CRRT-related variables (n=144, 61.81%)
      were the most common risk factors for dosing errors, whereas antibiotics (n=168,
      72.10%) were the medications most commonly associated with dosing errors.
      Pharmacist dosing adjustment resulted in a US$2,345.98 ICU cost savings per
      critically ill patient receiving CRRT. Suspected adverse drug events in the
      intervention group were significantly lower than those in the preintervention
      group (35 in 27 patients versus [vs] 18 in eleven patients, P<0.001). However,
      there was no significant difference between length of ICU stay and mortality
      after pharmacist dosing adjustment, which was 8.93 days vs 7.68 days (P=0.26) and
      30.10% vs 27.36% (P=0.39), respectively. CONCLUSION: Pharmacist dosing adjustment
      for patients receiving CRRT was well accepted by physicians, and was related with
      lower adverse drug event rates and ICU cost savings. These results may support
      the development of strategies to include a pharmacist in the multidisciplinary
      ICU team.

PMID- 24940065
TI  - Rotigotine is safe and efficacious in Atypical Parkinsonism Syndromes induced by
      both alpha-synucleinopathy and tauopathy.
AB  - Transdermal rotigotine (RTG) is a non-ergot dopamine agonist (D3>D2>D1), and is
      indicated for use in early and advanced Parkinson's disease (PD). RTG patch has
      many potential advantages due to the immediacy of onset of the therapeutic
      effect. Of note, intestinal absorption is not necessary and drug delivery is
      constant, thereby avoiding drug peaks and helping patient compliance. In turn,
      transdermal RTG seems a suitable candidate in the treatment of atypical
      Parkinsonian disorders (APS). Fifty-one subjects with a diagnosis of APS were
      treated with transdermal RTG. The diagnoses were: Parkinson's disease with
      dementia, multiple system atrophy Parkinsonian type, multiple system atrophy
      cerebellar type, progressive supranuclear palsy, corticobasal degeneration, Lewy
      body dementia, and frontotemporal dementia with Parkinsonism. Patients were
      evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS; part III),
      Neuropsychiatric Inventory (NPI), and mini-mental state examination (MMSE) and
      all adverse events (AEs) were recorded. Patients treated with RTG showed an
      overall decrease of UPDRS III scores without increasing behavioral disturbances.
      Main AEs were hypotension, nausea, vomiting, drowsiness, tachycardia, and
      dystonia. On the whole, 15 patients were affected by AEs and seven patients
      suspended RTG treatment due to AEs. The results show that transdermal RTG is
      effective with a good tolerability profile. RTG patch could be a good therapeutic
      tool in patients with APS. 

PMID- 24940067
TI  - Nature and frequency of medication errors in a geriatric ward: an Indonesian
      experience.
AB  - PURPOSE: To determine the nature and frequency of medication errors during
      medication delivery processes in a public teaching hospital geriatric ward in
      Bali, Indonesia. METHODS: A 20-week prospective study on medication errors
      occurring during the medication delivery process was conducted in a geriatric
      ward in a public teaching hospital in Bali, Indonesia. Participants selected were
      inpatients aged more than 60 years. Patients were excluded if they had a
      malignancy, were undergoing surgery, or receiving chemotherapy treatment. The
      occurrence of medication errors in prescribing, transcribing, dispensing, and
      administration were detected by the investigator providing in-hospital clinical
      pharmacy services. RESULTS: Seven hundred and seventy drug orders and 7,662 drug
      doses were reviewed as part of the study. There were 1,563 medication errors
      detected among the 7,662 drug doses reviewed, representing an error rate of
      20.4%. Administration errors were the most frequent medication errors identified
      (59%), followed by transcription errors (15%), dispensing errors (14%), and
      prescribing errors (7%). Errors in documentation were the most common form of
      administration errors. Of these errors, 2.4% were classified as potentially
      serious and 10.3% as potentially significant. CONCLUSION: Medication errors
      occurred in every stage of the medication delivery process, with administration
      errors being the most frequent. The majority of errors identified in the
      administration stage were related to documentation. Provision of in-hospital
      clinical pharmacy services could potentially play a significant role in detecting
      and preventing medication errors.

PMID- 24940068
TI  - Vascular quality of care pilot study: how admission to a vascular surgery service
      affects evidence-based pharmacologic risk factor modification in patients with
      lower extremity peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) guidelines recommend aggressive
      risk factor modification to improve cardiovascular outcomes. Recommended
      pharmacologic therapies include antiplatelets, angiotensin converting enzyme
      (ACE) inhibitors, and HMG-CoA-reductase inhibitors (statins). PURPOSE: We studied
      the degree to which patient admission to a vascular surgery service increased the
      use of these therapies. PATIENTS AND METHODS: The authors conducted a
      retrospective chart review of 150 patients with PAD admitted to the vascular
      surgery service at a large Canadian tertiary care hospital. The use of
      recommended pharmacologic therapies at the time of admission and discharge were
      compared. A multidisciplinary clinical team established criteria by which
      patients were deemed ineligible to receive any of the recommended therapies.
      Angiotensin receptor blockers (ARBs) were considered an alternative to ACE
      inhibitors. RESULTS: Prior to hospital admission, 64% of patients were on
      antiplatelet therapy, 67% were on an ACE inhibitor or ARB, and 71% were on a
      statin. At the time of discharge, 91% of patients were on an antiplatelet (or
      not, with an acceptable reason), 77% were on an ACE inhibitor or an ARB (or not,
      with an acceptable reason), and 85% were on a statin (or not, with an acceptable
      reason). While new prescriptions were largely responsible for improved guideline
      adherence with antiplatelets and statins, most of the apparent improvement in ACE
      inhibitor and ARB use was the result of identifying an acceptable reason for not
      having them prescribed. CONCLUSION: This hypothesis generating pilot study
      supports the findings of others that there is suboptimal prescription of
      pharmacologic risk reduction therapies in the PAD population. Admission to a
      vascular service increases these rates. Nevertheless, some patients are still not
      receiving evidence-based treatment at discharge even after consideration of
      acceptable reasons. Strategies are needed to improve PAD guideline adherence in
      both the community at large and the vascular surgery service.

PMID- 24940069
TI  - Prevalence and predictors of harmful khat use among university students in
      ethiopia.
AB  - Comprehensive assessment of harmful khat use is lacking because often researchers
      rely on a simple tool for studying it. The aim of this study was to determine the
      prevalence and predictors of harmful khat use among Ethiopian university students
      by developing a comprehensive scale based on Alcohol Use Identification Test,
      Severity of Dependency Syndrome scale, and International Classification of
      Diseases definition of harmful substance use. Logistic regression was performed
      to identify predictors of harmful khat use. One in five current khat user
      students were identified as harmful khat users [20.6% (95% CI: 14.3-22.3)].
      Harmful khat use in this study was strongly associated with chewing at commercial
      places [adjusted odds ratio (AOR) = 2.32 (95% CI: 1.01-5.33)], and having non
      student friends accompanying the khat-chewing ceremony [AOR = 3.77 (95% CI: 1.09
      13.03). Students who started chewing khat at the age of 20 years or later [AOR =
      0.19 (95% CI: 0.07-0.55)] and those who preferred to study in the library [AOR =
      0.31(95% CI: 0.12-0.81)] were less likely to be harmful khat users. The
      university authorities, in addition to provision of student guidance on substance
      use prevention, need to work in collaboration with the surrounding community and
      responsible public authorities in order to reduce harmful use of khat by their
      students. 

PMID- 24940070
TI  - Coping strategies in egyptian ladies with breast cancer.
AB  - INTRODUCTION: A diagnosis of breast cancer regardless of the stage can be
      stressful, impact multiple spheres of life, and disrupt physical status,
      emotional and spiritual well-being, and personal relationships for the patient
      and family. In order to adapt, the patient ought to employ certain coping
      mechanisms. Individuals with terminal illness who utilize coping strategies have
      better quality of life compared to those who do not. PATIENTS AND METHODS: This
      study aimed to determine the strategies used by females with breast cancer to
      cope with such stress by using Brief COPE scale and the hospital anxiety and
      depression scale. The study included 56 female patients diagnosed with operable
      breast cancer at Mansoura Oncology Center before surgery. RESULTS: Large
      proportion of patients used acceptance, religion, and emotional support in coping
      with the stress of having breast cancer. Patients with depressive symptoms scored
      significantly higher venting while those with anxiety scored higher positive
      reframing, planning, and venting. CONCLUSION: Efforts should be made to encourage
      women with breast cancer to use coping strategies that have been found to be
      helpful (eg, acceptance, emotional support, distraction, and active coping
      strategies).

PMID- 24940071
TI  - Overexpression of Abl2 predicts poor prognosis in hepatocellular carcinomas and
      is associated with cancer cell migration and invasion.
AB  - INTRODUCTION: Abl2 nonreceptor tyrosine kinase (Arg, c-abl oncogene 2) has
      recently been identified as being recurrently amplified at DNA levels and
      overexpressed at mRNA levels in hepatocellular carcinomas (HCCs), and might be a
      potential oncogenic driver and therapeutic target for HCC. METHODS: In this
      study, we investigated the Abl2 expression in a series of HCC tumors by
      immunohistochemistry and further evaluated its clinicopathological and prognostic
      significance. We also performed an in vitro experiment to validate the effect of
      Abl2 gene silencing on the migration and invasion abilities of human liver cancer
      HepG2 cells. RESULTS: It has been demonstrated that Abl2 was unregulated in 37.3%
      (28/75) of primary HCC tissues, and was significantly associated with a shorter
      overall survival time (P=0.0005). In addition, Abl2 gene silencing in HepG2 cells
      significantly attenuated its migration and invasion abilities in vitro. We also
      found that the phosphorylation of metastasis-associated gene cortactin was
      markedly decreased by Abl2 silencing. CONCLUSION: We propose that Abl2 might be a
      potential candidate therapeutic target for HCCs and that targeted therapies
      against Abl2 in the treatment of HCCs deserve further investigation in the
      future.

PMID- 24940072
TI  - High expression of 23 kDa protein of augmenter of liver regeneration (ALR) in
      human hepatocellular carcinoma.
AB  - BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide
      that participates in the process of liver regeneration. Two forms of ALR proteins
      are expressed in hepatocytes. Previous data have shown that ALR is essential for
      cell survival and has potential antimetastatic properties in hepatocellular
      carcinoma (HCC). AIMS: The study aimed to evaluate the expression levels of two
      forms of ALR proteins in HCC and their possible significance in HCC development.
      METHODS: Balb/c mouse monoclonal antibody against ALR protein was prepared in
      order to detect the ALR protein in HCC by Western blotting and
      immunohistochemistry. ALR mRNA expression levels were measured by real-time
      polymerase chain reaction in HCC tissues and compared to paracancerous liver
      tissues in 22 HCC patients. RESULTS: ALR mRNA expression in HCC liver tissues
      (1.51*10(6) copies/MUL) was higher than in paracancerous tissues (1.04*10(4)
      copies/MUL). ALR protein expression was also enhanced in HCC liver tissues. The
      enhanced ALR protein was shown to be 23 kDa by Western blotting.
      Immunohistochemical analysis showed that the 23 kDa ALR protein mainly existed in
      the hepatocyte cytosol. CONCLUSION: The 23 kDa ALR protein was highly expressed
      in HCC and may play an important role in hepatocarcinogenesis.

PMID- 24940073
TI  - miR-544a promotes the invasion of lung cancer cells by targeting cadherina 1 in
      vitro.
AB  - OBJECTIVE: To find out the effect of miR-544a on the invasion of lung cancer
      cells and to explore the underlying molecular mechanisms. METHODS: Micro
      ribonucleic acid (miRNA) expression in two different invasive lung cancer cell
      lines 95C (low invasive ability) and 95D (high invasive ability) was analyzed by
      miRNA microarray and real-time quantitative polymerase chain reaction (PCR); miR
      544a mimic was transfected to 95C, and its invasion ability was detected by
      transwell migration assay; we predicted the candidate miRNA target genes by
      TargetScan (Whitehead Institute for Biomedical Research, Cambridge, MA, USA)
      software and verified the target genes by Western blot. RESULTS: The expression
      of miR-544a was significantly increased in 95D in miRNA microarray and
      quantitative PCR tests (P<0.05). After being transfected with miR-544a mimic, the
      invasion ability of 95C was enhanced (P<0.01). Moreover, transfection with miR
      544a inhibitor decreased the invasion ability of 95D (P<0.01). miR-544a possibly
      combined with CDH1 (E-cadherin) predicted by the TargetScan analysis. 95C with
      miR-544a mimic reduced the expression of CDH1 and improved the expression of
      vimentin, while 95D with miR-544a inhibitor improved the expression of CDH1 and
      reduced the expression of vimentin. CONCLUSION: miR-544a can promote the invasion
      of non-small cell lung cancer by downregulation of CDH1 and upregulation of
      vimentin.

PMID- 24940074
TI  - The potential clinical applications and prospects of microRNAs in lung cancer.
AB  - Lung cancer is the major cause of cancer deaths worldwide due to its late
      diagnosis and poor outcome. Understanding genomic medicine may widen our vision
      into the oncogenesis of lung cancer and may open the door to improvements in the
      clinical management of lung cancer. It is well known that almost half of all
      genes are regulated by microRNAs (miRNAs). This review focuses on the role of
      miRNAs in lung cancer and also touches on the value of miRNA-based novel
      therapies for lung cancers. 

PMID- 24940076
TI  - Assessment of treatment response in chronic constipation clinical trials.
AB  - BACKGROUND: While chronic constipation (CC) clinical trials have focused
      primarily on bowel symptoms (symptoms directly related to bowel movements),
      abdominal symptoms are also prevalent among patients. The United States Food and
      Drug Administration's (FDA's) guidance on the use of patient-reported outcome
      measures to support product approvals or labeling claims recommends that
      endpoints be developed with direct patient input and include all symptoms
      important to patients. AIM: To identify a comprehensive set of CC symptoms that
      are important to patients for measurement in clinical trials. METHODS: Following
      a targeted literature review to identify CC symptoms previously reported by
      patients, 28 patient interviews were conducted consistent with the FDA's guidance
      on patient-reported outcomes. Subsequent to open-ended questions eliciting
      descriptions of all symptoms, rating and ranking methods were used to identify
      those of greatest importance to patients. RESULTS: All 67 studies reviewed
      included bowel symptoms; more than half also addressed at least one abdominal
      symptom. Interview participants reported 62 potentially distinct concepts: 12
      bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts.
      Patients' descriptions revealed that many symptom terms were highly related
      and/or could be considered secondary to CC. The rating and ranking task results
      suggest that both bowel (for example, stool frequency and consistency) and
      abdominal symptoms (for example, bloating, abdominal pain) comprise patients'
      most important symptoms. Further, improvements in both bowel and abdominal
      symptoms would constitute an improvement in patients' CC overall. CONCLUSION:
      Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and
      should also be addressed in clinical trials to fully evaluate treatment benefit.

PMID- 24940075
TI  - Effect of NQO1 C609T polymorphism on prostate cancer risk: a meta-analysis.
AB  - BACKGROUND: Some studies have found that the NAD(P)H: quinone oxidoreductase 1
      (NQO1) SNP609 is associated with an increased risk for several malignancies.
      Numerous epidemiological studies have evaluated the association between the NQO1
      C609T polymorphism and the risk of prostate cancer. However, the results of these
      studies have been conflicting. The aim of this study was to provide a more
      precise estimation of its relationship with prostate cancer using a meta
      analysis. METHODS: Electronic searches of several databases were conducted for
      all publications on the association between the NQO1 C609T polymorphism and
      prostate cancer before May 2013. The odds ratio (OR) and its 95% confidence
      interval (CI) were used for statistical analysis. RESULTS: A total of six studies
      with 717 cases and 1,794 controls were included. No significant association was
      found between the NQO1 C609T polymorphism and prostate cancer risk in the total
      population analysis. In subgroup meta-analysis by ethnicity, a positive
      association was found in an Asian subgroup (T versus C, OR 1.337, 95% CI 1.014
      1.763, P=0.040; TT + CT versus CC, OR 1.419, 95% CI 1.053-1.913, P=0.021).
      However, no significant association in any genetic models was observed in
      Caucasians. CONCLUSION: This meta-analysis showed that the NQO1 SNP609 T allele
      might be a risk factor for prostate cancer in Asians. However, this result should
      be verified by additional population-based studies with large sample sizes.

PMID- 24940077
TI  - How do hospitalization patterns of home hemodialysis patients compare with a
      reasonably well dialysis patient cohort?
AB  - BACKGROUND: The home hemodialysis (HHD) treatment option has been associated with
      improved patient outcomes compared to in-center hemodialysis (ICHD) programs.
      What is not quite clear is the influence of patient selection bias on the
      perceived benefits of HHD. The purpose of this study was to explore the potential
      benefits of HHD by comparing the admission patterns of HHD patients with a
      control group from a reasonably well dialysis patient cohort, which in this case
      were satellite hemodialysis patients on a Category 1 transplant waiting list
      (Cat1 SHD). METHODS: A single center retrospective randomized cohort study of HHD
      and Cat1 SHD patients who were on these two treatment modalities from August 2012
      to August 2013 was performed to obtain a sample of 25 patients for each group.
      RESULTS: The mean length of stay in hospital was 5.9 days for HHD patients and
      6.7 days for Cat1 SHD group (P=0.8). Eighteen admissions were observed for both
      groups (0.72 admissions/patient-year; P=0.5). HHD patients spent 71 days and Cat1
      SHD patients spent 85 days in hospital (2.8 and 3.4 days/patient-year
      respectively; P<0.005). The mean serum potassium level for HHD patients was 4.1
      (3.1-6.5) mEq/L versus 5.0 (3.7-6.1) mEq/L for Cat1 SHD patients (P=0.001) and
      the mean phosphate level was 1.1 (0.56-2.38) mg/dL and 1.5 (0.43-3.2) mg/dL
      (P=0.02) for the respective groups. CONCLUSION: This study confirms the
      superiority of the HHD treatment option in improving patient outcomes. Admission
      patterns of HHD patients fared very well against a control group which consisted
      of reasonably well dialysis patients.

PMID- 24940078
TI  - Reasons for encounter and diagnoses of new outpatients at a small community
      hospital in Japan: an observational study.
AB  - PURPOSE: Although many new patients are seen at small hospitals, there are few
      reports of new health problems from such hospitals in Japan. Therefore, we
      investigated the reasons for encounter (RFE) and diagnoses of new outpatients in
      a small hospital to provide educational resources for teaching general practice
      methods. METHODS: This observational study was conducted at the Department of
      General Internal Medicine in a small community hospital between May 6, 2010 and
      March 11, 2011. We classified RFEs and diagnoses according to component 1,
      "Symptoms/Complaints", and component 7, "Diagnosis/Diseases", of the
      International Classification of Primary Care, 2nd edition (ICPC-2). We also
      evaluated the differences between RFEs observed and common symptoms from the
      guidelines Model Core Curriculum for Medical Students and Goals of Clinical
      Clerkship. RESULTS: We analyzed the data of 1,515 outpatients. There were 2,252
      RFEs (1.49 per encounter) and 170 ICPC-2 codes. The top 30 RFE codes accounted
      for 80% of all RFEs and the top 55 codes accounted for 90%. There were 1,727
      diagnoses and 196 ICPC-2 codes. The top 50 diagnosis codes accounted for 80% of
      all diagnoses, and the top 90 codes accounted for 90%. Of the 2,252 RFEs, 1,408
      (62.5%) included at least one of the 36 symptoms listed in the Model Core
      Curriculum and 1,443 (64.1%) included at least one of the 35 symptoms in the
      Goals of Clinical Clerkship. On the other hand, "A91 Abnormal result
      investigation", "R21 Throat symptom/complaint", and "R07 Sneezing/nasal
      congestion", which were among the top 10 RFEs, were not included in these two
      guidelines. CONCLUSION: We identified the common RFEs and diagnoses at a small
      hospital in Japan and revealed the inconsistencies between the RFEs observed and
      common symptoms listed in the guidelines. Our findings can be useful in improving
      the general practice medical education curricula.

PMID- 24940079
TI  - Voices that may not otherwise be heard: a qualitative exploration into the
      perspectives of primary care patients living with chronic pain.
AB  - BACKGROUND: Although psychometrically sound pain assessment tools are available,
      there is a paucity of research that comprehensively defines chronic pain from the
      perspective of patients. The purpose of this study was to examine the utility of
      a combination of qualitative methods (Photovoice, one-on-one interviews, and
      focus groups) in examining the daily experiences of primary care patients living
      with chronic pain. METHODS: A sample of English-speaking primary care patients
      aged 30 years or older, who had been prescribed an opioid for long-term,
      noncancer pain management, participated in the study. Each patient took
      photographs that best reflected both his/her experiences with chronic pain and
      what he/she would like his/her life to be without chronic pain. RESULTS: Patients
      submitted an average of 20.2+/-3.1 photographs (range =8-27 photographs).
      Analysis of one-on-one interviews illuminated five dominant themes: daily need
      for multiple medications, including opioids; difficulties climbing a flight of
      stairs; struggling to get out of bed in the morning; extreme challenges with
      participating in day-to-day life activities; and experiencing feelings of
      hopelessness and helplessness on a regular basis. Seven themes emerged from the
      focus groups: undesired effects/burdens of medications, loss of/striving for
      independence, effect on social interactions/relationships, pain effect on
      activities of daily living, constant search for convenience/a better situation,
      interactions with physicians, and frustration/depression with pain. CONCLUSION:
      The qualitative methods employed in this study provide deep insight into
      perceptions and experiences of patients living with chronic pain that is vital
      for informing future clinical interventions.

PMID- 24940080
TI  - High plasma exposure to pemetrexed leads to severe hyponatremia in patients with
      advanced non small cell lung cancer receiving pemetrexed-platinum doublet
      chemotherapy.
AB  - BACKGROUND: Pemetrexed-platinum doublet therapy is a standard treatment for stage
      IIIb/IV nonsquamous non small cell lung cancer (NSCLC). While the regimen is
      associated with several grade >=3 toxicities, hyponatremia is not a commonly
      reported adverse effect. Here we report an unusually high incidence of grade >=3
      hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the
      pharmacological basis for this phenomenon. METHODS: Forty-six patients with
      advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed
      formulations. All patients received the pemetrexed-platinum doublet for six
      cycles followed by single-agent pemetrexed maintenance until progression.
      Pharmacokinetic blood samples were collected at predefined time points during the
      first cycle and the concentration-time profile of pemetrexed was investigated by
      noncompartmental analysis. Hyponatremic episodes were investigated with serum
      electrolytes, serum osmolality, urinary sodium, and urine osmolality. RESULTS:
      Sixteen of 46 patients (35%) had at least one episode of grade >=3 hyponatremia.
      Twenty-four episodes of grade >=3 hyponatremia were observed in 200 cycles of
      doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in
      patients with high-grade hyponatremia than in those with low-grade or no
      hyponatremia (P=0.063 and P=0.001, respectively). Pemetrexed clearance in high
      grade hyponatremia was quite low compared with normal and low-grade hyponatremia
      (P=0.001 and P=0.055, respectively). Median pemetrexed exposure in this cohort
      was much higher than that reported in the literature from Western studies.
      CONCLUSION: Higher exposure to pemetrexed is associated with grade >=3
      hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in
      Indian patients needs further investigation.

PMID- 24940081
TI  - Lipid profiles and ischemic stroke risk: variations by sex within racial/ethnic
      groups.
AB  - Evidence implicates lipid abnormalities as important but modifiable risk factors
      for stroke. This study assesses whether hypercholesterolemia can be used to
      predict the risk for etiologic subtypes of ischemic stroke between sexes within
      racial/ethnic groups. Data elements related to stroke risk, diagnosis, and
      outcomes were abstracted from the medical records of 3,290 acute stroke
      admissions between 2006 and 2010 at a regional stroke center. Sex comparison
      within racial/ethnic groups revealed that South Asian and Hispanic men had a
      higher proportion of ischemic stroke than women, while the inverse was true for
      Whites and African Americans (P=0.0014). All women, except South Asian women, had
      higher mean plasma total cholesterol and higher blood circulating low-density
      lipoprotein levels (>=100 mg/dL) than men at the time of their admissions. The
      incidence of large-artery atherosclerosis (LAA) was more common among women than
      men, except among Hispanics, where men tended to have higher incidences. A
      regression analysis that considered patients diagnosed with either LAA or small
      artery occlusion etiologic subtype as the outcomes and high-density lipoproteins
      and triglycerides as predictors showed inconsistent associations between lipid
      profiles and the incidence of these subtypes between the sexes within
      racial/ethnic groups. In conclusion, our investigation suggests that women stroke
      patients may be at increased risk for stroke etiologic subtype LAA than men.
      Although the higher prevalence of stroke risk factors examined in this study
      predicts the increase in the incidence of the disease, lack of
      knowledge/awareness and lack of affordable treatments for stroke risk factors
      among women and immigrants/non-US-born subpopulations may explain the observed
      associations. 

PMID- 24940082
TI  - Effect of hormonal contraceptives on lipid profile and the risk indices for
      cardiovascular disease in a Ghanaian community.
AB  - BACKGROUND: Hormonal contraceptives (HCs) have been shown to alter lipid profile
      among various population groups with different patterns of dyslipidemia and
      cardiovascular (CV) risk. The study aimed at determining the lipid profile
      pattern and CV risk in a Ghanaian cohort. METHODS: Purposive random sampling was
      done. Forty-seven and 19 cases were on oral contraceptives (OCs) and injectable
      contraceptives (ICs), respectively; five were on subdermal implant. Twenty-four
      non-users served as controls. Biodemographic and lipid profiles were determined.
      Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density
      lipoprotein cholesterol (LDLC), and very-low-density lipid lipoprotein
      cholesterol (VLDLC), were determined. Castelli index I and II were calculated.
      RESULTS: The mean age difference between the HC and control groups was
      insignificant. However, diastolic blood pressure (BP) differences were
      significant (P=0.006). The body mass index (BMI) of the OC and IC groups were
      significantly different from the control group (P=0.003 and P=0.008,
      respectively). TC levels for the control and case groups were 3.35+/-0.62 mmol/L
      and 4.07+/-0.91 mmol/L, respectively (P=0.002). LDLC levels for the control and
      case groups were 1.74+/-0.57 mmol/L and 2.38+/-0.84 mmol/L, respectively
      (P=0.003). Castelli index I (TC/HDLC) and II (LDLC/HDLC) were significantly
      different between the control and OC groups (P=0.026 and P=0.014, respectively).
      Spearman's rho correlation showed significant influence of HC use on TG
      (P=0.026), TC (P=0.000), LDLC (P=0.004), and VLDLC (P=0.026) over time.
      CONCLUSION: HC use is associated with significant increases in BMI, diastolic BP,
      TC, LDLC, and Castelli index I and II. These changes carry a potential risk in
      the development of CV disease.

PMID- 24940083
TI  - Sacral insufficiency fractures: a case of mistaken identity.
AB  - INTRODUCTION: Sacral insufficiency fractures are an important cause of lower back
      pain in the elderly. Clinically and radiologically, they must be distinguished
      from osseous metastases, which frequently coexist. To date, no case report has
      comprehensively explored the full range of diagnostic hurdles and potential
      pitfalls. CASE PRESENTATION: We report the case of a 70-year-old Caucasian female
      who presented to our services with a short history of progressive back pain
      without any history of trauma. A prior history of breast cancer was noted. Bone
      scintigraphy was initially reported as consistent with metastatic sacral
      deposits. Further characterization with magnetic resonance imaging and computed
      tomography revealed bilateral insufficiency fractures of the sacral alar. The
      patient responded well to conservative management. CONCLUSION: To avoid
      misdiagnosis, particularly in those who are also at risk of osseous metastases,
      sacral insufficiency fractures must always be considered as a cause of lower back
      pain.

PMID- 24940084
TI  - In vitro microdialysis membrane efficiency of broad-spectrum antibiotics in
      combination and alone.
AB  - PURPOSE: Microdialysis is a valuable technique for studying the distribution of
      drugs into interstitial fluid, the target site for a pharmacologic effect. Due to
      incomplete equilibrium, retrodialysis is a method used to correct for relative
      recovery. The impact of two-drug combinations on probe recovery, however, remains
      unknown. METHODS: In vitro microdialysis was conducted for five antibiotics
      (avibactam, cefepime, ceftaroline, piperacillin-tazobactam, and vancomycin),
      representing three empiric antimicrobial regimens, to assess the impact of two
      drug combinations on probe recovery. Recoveries were compared between single and
      two-drug treatments. RESULTS: Recoveries by gain and loss were linear with their
      molecular weight. During all gain experiments, recoveries were similar when
      tested alone or in combination with another antibiotic. Unacceptable differences
      in recovery by loss were observed for cefepime in the presence of vancomycin (
      21%) and vancomycin in the presence of piperacillin-tazobactam (-22%).
      CONCLUSION: Differences among in vitro recovery by loss suggest two-drug
      combinations may impact dialysate recovery during in vivo retrodialysis
      procedures, particularly when larger molecular weight drugs (ie, vancomycin) are
      involved. Importantly, there were no differences during gain experiments. In
      vitro studies, as performed here, should be conducted for each potential two-drug
      combination, prior to their combined use for in vivo retrodialysis.

PMID- 24940086
TI  - Clinical utility of the Covidien Closure FastTM Endovenous Radiofrequency
      Ablation Catheter.
AB  - The Closure FastTM Endovenous Radiofrequency Ablation Catheter is the latest
      version of a minimally invasive system for the treatment of patients with
      superficial venous disease. The Closure FastTM catheter heats the vein wall to
      120 degrees C, causing denaturation of the collagen of the vein wall and
      contraction of the vessel such that no blood can flow through it. Nearly one
      million systems have been sold since the product was launched. Many, if not all,
      patients can be treated under local anesthesia with the Closure FastTM catheter.
      Duplex ultrasound reports occlusion rates for the treated vein of 94%-98% at 1
      year and 85%-93% at 3 years. The system produces average postoperative pain
      scores of less than 2 out of 10 on a visual analog score. In the first
      postoperative week, 76% of patients do not require analgesia. Some 45% of
      patients return to normal activity on the first postoperative day. Serious
      complications appear to be rare following the Closure FastTM procedure. Transient
      paresthesia occurs in 0.2% of cases, thrombophlebitis in 1%-10%, and
      thromboembolic events in up to 1.4%, mainly heat-induced thrombosis. Closure
      FastTM adds significant costs to treating superficial venous disease but studies
      have shown it to be cost-effective when used in an office setting. 

PMID- 24940087
TI  - Comparative effectiveness of open versus minimally invasive sacroiliac joint
      fusion.
AB  - BACKGROUND: The mainstay of sacroiliac joint disruption/degenerative sacroiliitis
      therapy has been nonoperative management. This nonoperative management often
      includes a regimen of physical therapy, chiropractic treatment, therapeutic
      injections, and possibly radiofrequency ablation at the discretion of the
      treating physician. When these clinical treatments fail, sacroiliac joint fusion
      has been recommended as the standard treatment. Open and minimally invasive (MIS)
      surgical techniques are typical procedures. This study aims to compare the
      perioperative measures and Oswestry Disability Index (ODI) outcomes associated
      with each of these techniques. METHODS: A comparative retrospective chart review
      of patients with sacroiliac joint fusion and a minimum of 1 year of follow-up was
      performed. Perioperative measures and ODI scores were compared using the Fisher's
      exact test and two nonparametric tests, ie, the Mann-Whitney U test and the
      Wilcoxon signed-rank test. The results are presented as percent or median with
      range, as appropriate. RESULTS: Forty-nine patients from two institutions
      underwent sacroiliac joint fusion between 2006 and 2012. Ten patients were
      excluded because of incomplete data, leaving 39 evaluable patients, of whom 22
      underwent open and 17 underwent MIS sacroiliac joint fusion. The MIS group was
      significantly older (median age 66 [39-82] years) than the open group (median age
      51 [34-74] years). Surgical time and hospital stay were significantly shorter in
      the MIS group than in the open group. Preoperative ODI was significantly greater
      in the open group (median 64 [44-78]) than in the MIS group (median 53 [14-84]).
      Postoperative improvement in ODI was statistically significant within and between
      groups, with MIS resulting in greater improvement. CONCLUSION: The open and MIS
      sacroiliac joint fusion techniques resulted in statistically and clinically
      significant improvement for patients with degenerative sacroiliitis refractory to
      nonoperative management. However, the number of patients reaching the minimal
      clinically important difference and those showing overall improvement were
      greater in the MIS group.

PMID- 24940085
TI  - Advances in stent technologies and their effect on clinical efficacy and safety.
AB  - The introduction of intracoronary stents represented a major advance in
      interventional cardiology. While bare metal stents set the benchmark for improved
      safety over angioplasty, intimal hyperplasia and subsequent restenosis were
      important limitations. First-generation drug-eluting stents demonstrated
      significant improvements in efficacy, but not necessarily safety, and further
      technologic developments have focused on optimizing both. Current advances and
      understanding in stent design continue to improve on these concepts. This review
      summarizes past and present technology with particular emphasis on the principles
      underlying the efficacy and safety of drug-eluting stents, and offers a glimpse
      into the next generations of stents aimed at treating symptomatic coronary artery
      disease. 

PMID- 24940088
TI  - Indications for surgical removal of the eye in rural areas in cameroon.
AB  - OBJECTIVE: To determine the main clinical indications for surgical removal of the
      eye in rural areas in Cameroon. DESIGN: Retrospective non-comparative case
      series. PARTICIPANTS: A total of 253 patients presenting to the Manna eye clinic
      Nkongsamba who underwent destructive eye surgery (DES) between January 2006 and
      December 2010 were reviewed. MAIN OUTCOME MEASURE: Age, gender, occupation, prior
      medication, visual acuity, operation indications, and type of operation. RESULTS:
      There were 58.10% (n = 147) men and 41.90% (n = 106) women. Median age was 29
      years (interquartile range: 14-69 years); age ranged from 10 to 88 years. A total
      of 67.19% (n = 170) of participants were farmers and lived in rural zones. In
      all, 79.05% (n = 200) confessed to have trying a medication before the
      presentation. Surgical indications included infective causes (perforated corneal
      ulcer 33.20% (n = 84) and endophthalmitis 18.20% (n = 46)), trauma 17.40% (n =
      44), painful blind eyes 11.50% (n = 29), malignancy 10.70% (n = 27), and others
      9.10% (n = 23). CONCLUSION: The most common causes of DES in this series could be
      avoided. Therefore, preventive measures including extensive health education of
      the public and traditional healers on the risks linked to the use of traditional
      medicines in ophthalmology and the late presentation of eye disease, quality
      control of the campaigns that offer free cataract operations in the country.

PMID- 24940089
TI  - Thoracic epidural teratoma: case report and review of the literature.
AB  - PURPOSE: Spinal teratomas comprise a rare subset of spinal cord tumors, and here,
      we describe an even rarer childhood thoracic extradural-intracanalicular
      teratoma. The clinical presentation, management, and pathophysiology of these
      tumors are reviewed to promote recognition and guide treatment of these lesions.
      METHODS: We report the case of a 21-month-old boy who presented with marked
      spasticity, as well as failure to ambulate and meet motor milestones.
      Additionally, we provide a literature review of spinal teratomas, including their
      clinical presentation, work-up, pathophysiology, and underlying genetics.
      RESULTS: An MRI of the spine revealed a large dorsal epidural tumor extending
      from T3 to T10 with heterogeneous contrast enhancement and severe spinal cord
      compression. The tumor was resected revealing a cystic mass with tissue
      resembling hair, muscle, as well as cartilage; pathology confirmed the diagnosis
      of teratoma. Gross total resection was achieved, and the child eventually gained
      ambulatory function. CONCLUSIONS: Given that spinal teratomas are rare entities
      that can present with significant neurologic compromise, they must remain on
      clinicians' differentials. Unfortunately, the exact origin of these tumors
      remains inconclusive and requires further investigation.

PMID- 24940091
TI  - Utilization of stereotactic ablative radiotherapy in the management of
      oligometastatic disease.

PMID- 24940090
TI  - A case of giant osteoma in the middle turbinate of a child.
AB  - Only seven cases of osteoma arising in the middle turbinate have been reported to
      date. We report the eighth case, involving osteoma in the middle turbinate of a
      child. This young boy was initially examined at the age of nine for the main
      complaint of nasal obstruction. Although a large osteoma with a maximum diameter
      of 30 mm was observed on computed tomography (CT), the patient was only observed
      because of the wishes of the family. At 13 years, he was again examined, as a
      result of worsening of the nasal obstruction. CT revealed that the osteoma had
      enlarged to a maximum diameter of 41 mm. Endoscopic surgery was attempted, but
      because of difficulties, the osteoma instead had to be removed under direct
      vision via a gingival incision. The final pathological diagnosis was osteoid
      osteoma. The nasal obstruction disappeared following surgery, with no recurrence
      after more than 12 months postoperatively. 

PMID- 24940092
TI  - A comparison of the risks of in-breast recurrence after a diagnosis of dcis or
      early invasive breast cancer.
AB  - BACKGROUND: It is controversial whether ductal carcinoma in situ (dcis) is a
      preinvasive marker of breast cancer or if it is part of a spectrum of small
      cancers with malignant potential. Comparing clinical outcomes in women with
      invasive and noninvasive breast lesions might help to resolve the issue. METHODS:
      From a database of 2641 patients with breast cancer, we selected women who had
      been treated with breast-conserving surgery for a cancer that was 2.0 cm or less
      in size, node-negative, and nonpalpable. No subject received chemotherapy.
      Cancers were categorized as noninvasive (stage 0, n = 172) or invasive (stage 1,
      n = 401) based on a review of the pathology records. We compared the actuarial
      risks of in-breast recurrence after invasive and noninvasive breast lesions
      before and after adjusting for tamoxifen and radiotherapy. RESULTS: The 18-year
      cumulative risk of in-breast recurrence was 35.2% for patients with dcis and
      12.8% for patients with small invasive cancers (hazard ratio: 2.4; 95% confidence
      interval: 1.5 to 3.8; p < 0.0003). After adjustment for radiotherapy and
      tamoxifen treatment, the difference was small and nonsignificant (hazard ratio:
      1.4; 95% confidence interval: 0.9 to 2.4; p = 0.22). CONCLUSIONS: For women with
      small, nonpalpable, node-negative breast cancers, the likelihood of experiencing
      an in-breast recurrence was associated with radiotherapy and with tamoxifen, but
      not with the presence of cancer cells invading beyond the basement membrane.

PMID- 24940095
TI  - Two indicators of hospital resource efficiency in cancer care.

PMID- 24940093
TI  - Effect of preoperative chemoradiotherapy on outcome of patients with locally
      advanced esophagogastric junction adenocarcinoma-a pilot study.
AB  - BACKGROUND: To date, few studies of preoperative chemotherapy or
      chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been
      statistically powered; indeed, gej tumours have thus far been grouped with
      esophageal or gastric cancer in phase iii trials, thereby generating conflicting
      results. METHODS: We studied 41 patients affected by locally advanced Siewert
      type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen
      [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent
      computed tomography-based three-dimensional conformal radiotherapy delivered
      using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed
      by surgery. Completeness of tumour resection (performed approximately 6 weeks
      after completion of crt), clinical and pathologic response rates, and safety and
      outcome of the treatment were the main endpoints of the study. RESULTS: All 41
      patients completed preoperative treatment. Combined therapy was well tolerated,
      with no treatment-related deaths. Dose reduction was necessary in 8 patients
      (19.5%). After crt, 78% of the patients showed a partial clinical response, 17%
      were stable, and 5% experienced disease progression. Pathology examination of
      surgical specimens demonstrated a 10% complete response rate. The median and mean
      survival times were 26 and 36 months respectively (95% confidence interval: 14 to
      37 months and 30 to 41 months respectively). On multivariate analysis, TNM
      staging and clinical response were demonstrated to be the only independent
      variables related to long-term survival. CONCLUSIONS: In our experience,
      preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej
      adenocarcinoma, but shows mild efficacy, as suggested by the low rate of
      pathologic complete response.

PMID- 24940096
TI  - How has acute oncology improved care for patients?
AB  - A United Kingdom-wide appreciation of the systemic failings of emergency cancer
      care led to the creation of a new subspecialty, acute oncology. It was meant to
      bridge the gap between admitting teams, oncology, and palliative care, providing
      support to manage the symptoms of cancer, the side effects of cancer treatment,
      and people presenting with cancer of unknown primary origin. This article
      identifies the reasons for the creation of acute oncology and explores various
      models for this aspect of cancer care worldwide. With health care budgets static
      and demand increasing, the article also identifies ways in which acute oncology
      can contribute to an efficient and caring health system. 

PMID- 24940097
TI  - Ottawa Cardiac Oncology Program wins 2013 Cancer Quality Council of Ontario
      Innovation Award.

PMID- 24940094
TI  - Cancer and venous thromboembolic disease: from molecular mechanisms to clinical
      management.
AB  - Venous thromboembolism (vte) represents a major challenge in the management of
      patients with cancer. The malignant phenotype is associated with derangements in
      the coagulation cascade that can manifest as thrombosis, hemorrhage, or
      disseminated intravascular coagulation. The risk of vte is increased by a factor
      of approximately 6 in patients with cancer compared with non-cancer patients, and
      cancer patients account for approximately 20% of all newly diagnosed cases of
      vte. Postmortem studies have demonstrated rates of vte in patients with cancer to
      be as high as 50%. Despite that prevalence, vte prophylaxis is underused in
      hospitalized patients with cancer. Studies have demonstrated that hospitalized
      patients with cancer are less likely than their non-cancer counterparts to
      receive vte prophylaxis. Consensus guidelines address the aforementioned issues
      and emerging concepts in the area, including the use of risk-assessment models,
      biomarkers to identify patients at highest risk of vte, and use of anticoagulants
      as anticancer therapy. Despite those guidelines, a gulf exists between current
      recommendations and clinical practice; greater efforts are thus required to
      ensure effective implementation of strategies to reduce the incidence of vte in
      patients with cancer. 

PMID- 24940098
TI  - Clinical manifestations in patients with alpha-fetoprotein-producing gastric
      cancer.
AB  - BACKGROUND: Patients with alpha-fetoprotein (afp)-producing gastric cancer have a
      high incidence of liver metastasis and poor prognosis. There is some controversy
      about clinical manifestations in these patients. METHODS: Our study enrolled
      patients who, before surgery, had gastric cancer with serum afp exceeding 20
      ng/mL [afp>20 (n = 58)] and with serum afp 20 ng/mL or less [afp<=20 (n = 1236)].
      Clinical manifestations were compared between the groups. RESULTS: Early gastric
      cancer was more frequent (30.1% vs. 4%) and advanced gastric cancer was less
      frequent (69.9% vs. 96%) in the afp<=20 group than the afp>20 group (p < 0.001).
      Liver and lymph node metastasis occurred less frequently in the afp<=20 group
      (4.4% vs. 27.6%, p < 0.001, and 60.7% vs. 91.4%, p < 0.001, respectively). The 1
      , 3-, 5-, and 10-year survival rates of afp<=20 patients were 75.2%, 53.4%,
      45.8%, and 34.6% respectively. The 1-, 3-, 5-, and 10-year survival rates of
      patients with afp greater than 20 ng/mL, but 300 ng/mL or less, were 46.7%,
      28.9%, 17.8%, and 13.3% respectively. The 1-, 3-, and 5-year survival rates of
      patients with serum afp greater than 300 ng/mL were 15.4%, 7.7%, and 0%
      respectively. The independent predictors for survival time were afp
      concentration, age, peritoneal seeding, liver metastasis, lymph node metastasis,
      vascular invasion, TNM stage, curative surgery, serosal invasion, and Lauren
      classification. CONCLUSIONS: Patients with high serum afp had a high frequency of
      liver and lymph node metastasis and very poor prognosis. More aggressive
      management with multimodal therapy (for example, chemotherapy, radiotherapy)
      might be needed when treating such patients.

PMID- 24940099
TI  - Treatment outcomes for male breast cancer: a single-centre retrospective case
      control study.
AB  - BACKGROUND: Male breast cancer (bc) is a rare disease, and the availability of
      information on treatment outcomes is limited compared with that for female bc.
      The objective of the present study was to compare disease-free (dfs) and overall
      survival (os) for men compared with women having early-stage bc. METHODS: This
      retrospective case-control study compared men and women treated for stage 0-iiib
      bc at a single institution between 1981 and 2009. Matching was based on age at
      diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data
      were collected. Kaplan-Meier analysis was used to calculate os and dfs. RESULTS:
      For the 144 eligible patients (72 men, 72 women), median age at diagnosis was
      66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men,
      44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57
      women). Mean dfs was 127 months for women compared with 93 months for men (p =
      0.62). Mean os was 117 months for women compared with 124 months for men (p =
      0.35). In multivariate analysis, the only parameter that affected both dfs and os
      was stage at diagnosis. CONCLUSIONS: This case-control study is one of the
      largest to report treatment outcomes in early-stage male bc patients treated in a
      non-trial setting. Male patients received systemic therapy that was comparable to
      that received by their female counterparts, and they had similar os and dfs.
      These results add to current evidence from population studies that male sex is
      not a poor prognostic factor in early-stage breast cancer.

PMID- 24940100
TI  - Concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with
      concurrent chemoradiotherapy alone for the treatment of locally advanced
      nasopharyngeal carcinoma: a retrospective controlled study.
AB  - OBJECTIVE: We evaluated the survival benefit of providing concurrent
      chemoradiotherapy (ccrt) plus adjuvant chemotherapy compared with ccrt alone to
      patients with locally advanced nasopharyngeal carcinoma. METHODS: This
      retrospective study included 130 patients with nasopharyngeal carcinoma treated
      with ccrt plus adjuvant chemotherapy from June 2005 to December 2010. Another 130
      patients treated with ccrt alone during the same period were matched on age, sex,
      World Health Organization histology, T stage, N stage, and technology used for
      radiotherapy. The endpoints included overall survival, locoregional failure-free
      survival, distant metastasis failure-free survival, and failure-free survival.
      RESULTS: At a mean follow-up of 42.1 months (range: 8-85 months), the observed
      hazard ratios for the group receiving ccrt plus adjuvant chemotherapy compared
      with the group receiving ccrt alone were: for overall survival, 0.77 [95%
      confidence interval (ci): 0.37 to 1.57]; for locoregional failure-free survival,
      1.00 (95% ci: 0.37 to 2.71); for distant metastasis failure-free survival, 1.15
      (95% ci: 0.56 to 2.37); and for failure-free survival, 1.26 (95% ci: 0.69 to
      2.28). There were no significant differences in survival between the groups.
      After stratification by disease stage, ccrt plus adjuvant chemotherapy provided a
      borderline significant benefit for patients with N2-3 disease (hazard ratio:
      0.35; 95% ci: 0.11 to 1.06; p = 0.052). Multivariate analyses indicated that only
      tumour stage was a prognostic factor for overall survival. CONCLUSIONS: Patients
      with locally advanced nasopharyngeal carcinoma received no significant survival
      benefit from the addition of adjuvant chemotherapy to ccrt. However, patients
      with N2-3 disease might benefit from the addition of adjuvant chemotherapy to
      ccrt.

PMID- 24940101
TI  - Factors associated with breast cancer mortality after local recurrence.
AB  - PURPOSE: We aimed to identify risk factors for mortality after local recurrence
      in women treated for invasive breast cancer with breast-conserving surgery.
      EXPERIMENTAL DESIGN: Our prospective cohort study included 267 women who were
      treated with breast-conserving surgery at Women's College Hospital from 1987 to
      1997 and who later developed local recurrence. Clinical information and tumour
      receptor status were abstracted from medical records and pathology reports.
      Patients were followed from the date of local recurrence until death or last
      follow-up. Survival analysis used a Cox proportional hazards model. RESULTS:
      Among the 267 women with a local recurrence, 97 (36.3%) died of breast cancer
      within 10 years (on average 2.6 years after the local recurrence). The actuarial
      risk of death was 46.1% at 10 years from recurrence. In a multivariable model,
      predictors of death included short time from diagnosis to recurrence [hazard
      ratio (hr) for <5 years compared with >=10 years: 3.40; 95% confidence interval
      (ci): 1.04 to 11.1; p = 0.04], progesterone receptor positivity (hr: 0.35; 95%
      ci: 0.23 to 0.54; p < 0.001), lymph node positivity (hr: 2.1; 95% ci: 1.4 to 3.3;
      p = 0.001), and age at local recurrence (hr for age >45 compared with age <=45
      years: 0.61; 95% ci: 0.38 to 0.95; p = 0.03). CONCLUSIONS: The risk of death
      after local recurrence varies widely. Risk factors for death after local
      recurrence include node positivity, progesterone receptor negativity, young age
      at recurrence, and short time from diagnosis to recurrence.

PMID- 24940102
TI  - Access to personalized medicine: factors influencing the use and value of gene
      expression profiling in breast cancer treatment.
AB  - Genomic information is increasingly being used to personalize health care. One
      example is gene expression profiling (gep) tests, which estimate recurrence risk
      to inform chemotherapy decisions in breast cancer. Recently, gep tests were
      publicly funded in Ontario. We explored the perceived utility of gep tests,
      focusing on the factors influencing their use and value in treatment decision
      making by patients and oncologists. METHODS: We conducted interviews with
      oncologists (n = 14) and interviews and a focus group with early-stage breast
      cancer patients (n = 28) who underwent gep testing. Both groups were recruited
      through oncology clinics in Ontario. Data were analyzed using the content
      analysis and constant comparison techniques. RESULTS: Narratives from patients
      and oncologists provided insights into various factors facilitating and
      restricting access to gep. First, oncologists are positioned as gatekeepers of
      gep, providing access in medically appropriate cases. However, varying
      perceptions of appropriateness led to perceived inequities in access and negative
      impacts on the doctor-patient relationship. Second, media attention facilitated
      patient awareness of gep, but also complicated gatekeeping. Third, the dedicated
      administration attached to gep was burdensome and led to long waits for results
      and also to increased patient anxiety and delayed treatment. Collectively,
      because of barriers to access, those factors inadvertently heightened the
      perceived value of gep for patients relative to other prognostic indicators.
      CONCLUSIONS: Our study delineates the factors facilitating and restricting access
      to gep, and highlights the roles of media and organization of services in the
      perceived value and utilization of gep. The results identify a need for
      administrative changes and practice guidelines to support streamlined and
      standardized use of gep tests.

PMID- 24940103
TI  - Non-myeloablative allogeneic hematopoietic transplantation for patients with
      hematologic malignancies: 9-year single-centre experience.
AB  - Matched related and unrelated allogeneic nonmyeloablative hematopoietic
      transplantation (nmt) is increasingly being used in patients with hematologic
      malignancies. Conditioning regimens and indications for nmt vary considerably
      from centre to centre. Our institution uses intravenous fludarabine and
      cyclophosphamide, plus graft-versus-host disease (gvhd) prophylaxis with
      tacrolimus and mycophenolate mofetil. We retrospectively analyzed 89 consecutive
      patients who underwent nmt (65 related, 24 unrelated) at our institution from
      October 2002 to September 2011. The most frequent indications for nmt were acute
      myelocytic leukemia (high-risk in first complete or subsequent remission: n = 20,
      22.5%) and relapsed follicular lymphoma (n = 18, 20.2%). The cumulative incidence
      of acute gvhd (grades 2-4) was 28.1% (n = 25), and rates were similar for related
      (n = 18, 28%) and unrelated (n = 7, 29%) nmt. At a median follow-up of 22.6
      months, the cumulative incidence of chronic gvhd (limited and extensive) was 68%
      (n = 61): 68.5% (n = 44) for related and 71% (n = 17) for unrelated nmt. The 100
      day transplant-related mortality rate was 2.2%: 1.5% for related and 4.2% for
      unrelated nmt. Of the 89 patients, 30 (33.7%) have relapsed: 41.5% after related
      and 12.5% after unrelated nmt. Relapse rates were similar in patients with
      myeloid and lymphoid malignancies (36.4% vs. 33.3%). The 3-year overall and
      progression-free survival rates were 50.0% and 43.4% respectively, with
      multivariate analysis showing that neither rate was affected by age, disease
      group, status at transplantation, or related compared with unrelated nmt. Our
      findings indicate that, despite its limitations, including the incidence of
      chronic gvhd, nmt is an important treatment modality for a selected subgroup of
      patients with hematologic malignancies. 

PMID- 24940104
TI  - Use of screening tests, diagnosis wait times, and wait-related satisfaction in
      breast and prostate cancer.
AB  - BACKGROUND: Understanding factors relating to the perception of wait time by
      patients is key to improving the patient experience. METHODS: We surveyed 122
      breast and 90 prostate cancer patients presenting at clinics or listed on the
      cancer registry in Newfoundland and Labrador and reviewed their charts. We
      compared the wait time (first visit to diagnosis) and the wait-related
      satisfaction for breast and prostate cancer patients who received regular
      screening tests and whose cancer was screening test-detected ("screen/screen");
      who received regular screening tests and whose cancer was symptomatic
      ("screen/symptomatic"); who did not receive regular screening tests and whose
      cancer was screen test-detected ("no screen/screen"); and who did not receive
      regular screening tests and whose cancer was symptomatic ("no
      screen/symptomatic"). RESULTS: Although there were no group differences with
      respect to having a long wait (greater than the median of 47.5 days) for breast
      cancer patients (47.8% screen/screen, 54.7% screen/symptomatic, 50.0% no screen/
      screen, 40.0% no screen/symptomatic; p = 0.814), a smaller proportion of the
      screen/symptomatic patients were satisfied with their wait (72.5% screen/ screen,
      56.4% screen/symptomatic, 100% no screen/ screen, 90.9% no screen/symptomatic; p
      = 0.048). A larger proportion of screen/symptomatic prostate cancer patients had
      long waits (>104.5 days: 41.3% screen/screen, 92.0% screen/symptomatic, 46.0% no
      screen/screen, 40.0% no screen/symptomatic; p = 0.011) and a smaller proportion
      of screen/ symptomatic patients were satisfied with their wait (71.2%
      screen/screen, 30.8% screen/symptomatic, 76.9% no screen/screen, 90.9% no
      screen/symptomatic; p = 0.008). CONCLUSIONS: Diagnosis-related wait times and
      satisfaction were poorest among patients who received regular screening tests but
      whose cancer was not detected by those tests.

PMID- 24940105
TI  - One compared with two cycles of mitomycin C in chemoradiotherapy for anal cancer:
      analysis of outcomes and toxicity.
AB  - BACKGROUND: Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C
      (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol
      in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation.
      However, administration of the second bolus of mmc has been based largely on
      centre preference. Given limited published data on outcomes with different mmc
      regimens, our objective was to compare the efficacy and toxicity of 1 compared
      with 2 cycles of mmc in acc treatment. METHODS: Our retrospective study evaluated
      169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at
      two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and
      with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free
      (dfs) and overall survival (os) were analyzed. RESULTS: Baseline demographics,
      performance status, and stage were similar in the groups of patients who received
      mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were
      comparable, except for white blood cell count, which was higher in the mmc2
      group, but within normal range. The 5-year os and dfs were similar (75.1% and
      54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively).
      On multivariate analysis, mmc2 was the factor most strongly associated with
      specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01),
      grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations
      secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001). CONCLUSIONS: In
      definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes
      similar to those achieved with 2 cycles, with significantly less acute toxicity.

PMID- 24940106
TI  - Health care costs for prostate cancer patients receiving androgen deprivation
      therapy: treatment and adverse events.
AB  - BACKGROUND: Serious adverse events have been associated with androgen deprivation
      therapy (adt) for prostate cancer (pca), but few studies address the costs of
      those events. METHODS: All pca patients (ICD-9-CM 185) in Ontario who started 90
      days or more of adt or had orchiectomy at the age of 66 or older during 1995-2005
      (n = 26,809) were identified using the Ontario Cancer Registry and drug and
      hospital data. Diagnosis dates of adverse events-myocardial infarction, acute
      coronary syndrome, congestive heart failure, stroke, deep vein thrombosis or
      pulmonary embolism, any diabetes, and fracture or osteoporosis-before and after
      adt initiation were determined from administrative data. We excluded patients
      with the same diagnosis before and after adt, and we allocated each patient's
      time from adt initiation to death or December 31, 2007, into health states: adt
      (no adverse event), adt-ae (specified single adverse event), Multiple (>1 event),
      and Final (<=180 days before death). We used methods for Canadian health
      administrative data to estimate annual total health care costs during each state,
      and we examined monthly trends. RESULTS: Approximately 50% of 21,811 patients
      with no pre-adt adverse event developed 1 or more events after adt. The costliest
      adverse event state was stroke ($26,432/year). Multiple was the most frequent (n
      = 2,336) and the second most costly health state ($24,374/year). Costs were
      highest in the first month after diagnosis (from $1,714 for diabetes to $14,068
      for myocardial infarction). Costs declined within 18 months, ranging from $784
      per 30 days (diabetes) to $1,852 per 30 days (stroke). Adverse events increased
      the costs of adt by 100% to 265%. CONCLUSIONS: The economic burden of adverse
      events is relevant to programs and policies from clinic to government, and that
      burden merits consideration in the risks and benefits of adt.

PMID- 24940107
TI  - Survivorship care plans: a work in progress.
AB  - BACKGROUND: Health agencies across the world have echoed the recommendation of
      the U.S. Institute of Medicine (iom) that survivorship care plans (scps) should
      be provided to patients upon completion of treatment. To date, reviews of scps
      have been limited to the United States. The present review offers an expanded
      scope and describes how scps are being designed, delivered, and evaluated in
      various countries. METHODS: We collected scps from Canada, the United States,
      Europe, the United Kingdom, Australia, and New Zealand. We selected for analysis
      the scps for which we could obtain the actual scp, information about the delivery
      approach, and evaluation data. We conducted a content analysis and compared the
      scps with the iom guidelines. RESULTS: Of 47 scps initially identified, 16 were
      analyzed. The scps incorporated several of the iom's guidelines, but many did not
      include psychosocial services, identification of a key point of contact, genetic
      testing, and financial concerns. The model of delivery instituted by the U.K.
      National Cancer Survivorship Initiative stands out because of its unique approach
      that initiates care planning at diagnosis and stratifies patients into a follow
      up program based on self-management capacities. SUMMARY: There is considerable
      variation in the approach to delivery and the extent to which scps follow the
      original recommendations from the iom. We discuss the implications of this review
      for future care-planning programs and prospective research. A holistic approach
      to care that goes beyond the iom recommendations and that incorporates care
      planning from the point of diagnosis to beyond completion of treatment might
      improve people's experience of cancer care.

PMID- 24940109
TI  - Use of dexamethasone in patients with high-grade glioma: a clinical practice
      guideline.
AB  - BACKGROUND: Dexamethasone is the corticosteroid most commonly used for the
      management of vasogenic edema and increased intracranial pressure in patients
      with brain tumours. It is also used after surgery (before embarking on
      radiotherapy), particularly in patients whose tumours exert significant mass
      effect. Few prospective clinical trials have set out to determine the optimal
      dose and schedule for dexamethasone in patients with primary brain tumours, and
      subsequently, fewer clinical practice guideline recommendations have been
      formulated. METHODS: A review of the scientific literature published to November
      2012 considered all publications that addressed dexamethasone use in adult
      patients with brain tumours. Evidence was selected and reviewed by a working
      group comprising 3 clinicians and 1 methodologist. The resulting draft guideline
      underwent internal review by members of the Alberta Provincial cns Tumour Team,
      and feedback was incorporated into the final version of the guideline.
      RECOMMENDATIONS: Based on the evidence available to date, the Alberta Provincial
      cns Tumour Team makes these recommendations: Treatment with dexamethasone is
      recommended for symptom relief in adult patients with primary high-grade glioma
      and cerebral edema.After surgery, a maximum dose of 16 mg daily, administered in
      4 equal doses, is recommended for symptomatic patients. This protocol should
      ideally be started by the neurosurgeon.A rapid dexamethasone tapering schedule
      should be considered where appropriate.Patients who have high-grade tumours, are
      symptomatic, or have poor life expectancy, can be maintained on a 0.5-1.0 mg dose
      of dexamethasone daily.Side effects with dexamethasone are common, and they
      increase in frequency and severity with increased dose and duration of therapy.
      Patients should be carefully monitored for endocrine, muscular, skeletal,
      gastrointestinal, psychiatric, and hematologic complications, and for infections
      and other general side effects.

PMID- 24940111
TI  - Kissing and hpv: honest popular visions, the human papilloma virus, and cancers.

PMID- 24940108
TI  - The role of interventional radiology in the management of hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (hcc) is one of the most common causes of
      cancer-related death worldwide. Overall, liver transplantation and resection are
      the only available treatments with potential for cure. Various locoregional
      therapies are widely used to manage patients with advanced hcc or as a bridging
      therapy for patients with early and intermediate disease. This article reviews
      and evaluates the role of interventional radiology in the management of such
      cases by assessing various aspects of each method, such as effect on rates of
      survival, recurrence, tumour response, and complications. METHODS: A systemic
      search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of
      Systematic Reviews retrieved all related scientific papers for review. RESULTS:
      Needle core biopsy is a highly sensitive, specific, and accurate method for hcc
      grading. Portal-vein embolization provides adequate expansion of the future liver
      remnant, making more patients eligible for resection. In focal or multifocal
      unresectable early-stage disease, radiofrequency ablation tops all other
      thermoablative methods. However, microwave ablation is preferred in large tumours
      and in patients with Child-Pugh B disease. Cryoablation is preferred in recurrent
      disease and in patients who are poor candidates for anesthesia. Of the various
      transarterial modalities-transarterial chemoembolization (tace), drug-eluting
      beads, and transarterial radio-embolization (tare)-tace is the method of choice
      in Child-Pugh A disease, and tare is the method of choice in hcc cases with
      portal vein thrombosis. CONCLUSIONS: The existing data support the importance of
      a multidisciplinary approach in hcc management. Large randomized controlled
      studies are needed to provide clear indication guidelines for each method.

PMID- 24940110
TI  - Evidence-based guidance on venous thromboembolism in patients with solid tumours.
AB  - Venous thromboembolism (vte) is a serious, life-threatening complication of
      cancer. Anticoagulation therapy such as low molecular weight heparin (lmwh) has
      been shown to treat and prevent vte. Cancer therapy is often complex and ongoing,
      making the management of vte less straightforward in patients with cancer. There
      are no published Canadian guidelines available to suggest appropriate strategies
      for the management of vte in patients with solid tumours. We therefore aimed to
      develop a clear, evidence-based guideline on this topic. A systematic review of
      clinical trials and meta-analyses published between 2002 and 2013 in PubMed was
      conducted. Reference lists were hand-searched for additional publications. The
      National Guidelines Clearinghouse was searched for relevant guidelines.
      Recommendations were developed based on the best available evidence. In patients
      with solid tumours, lmwh is recommended for those with established vte and for
      those without established vte but with a high risk for developing vte. Options
      for lmwh include dalteparin, enoxaparin, and tinzaparin. No one agent can be
      recommended over another, but in the setting of renal insufficiency, tinzaparin
      is preferred. Unfractionated heparin can be used under select circumstances only
      (that is, when rapid clearance of the anticoagulant is desired). The most common
      adverse event is bleeding, but major events are rare, and with appropriate follow
      up care, bleeding can be monitored and appropriately managed. 

PMID- 24940112
TI  - Hormonal manipulation with letrozole in the treatment of metastatic malignant
      pecoma.
AB  - Perivascular epithelioid cell tumours (pecomas) are rare mesenchymal tumours.
      Some have a benign course; others metastasize. Treatment of malignant pecomas is
      challenging, and little is known about treatment for patients with metastatic
      disease. Here, we report a case of metastatic malignant pecoma with estrogen and
      progesterone receptor expression that showed a favourable and sustained response
      to letrozole. 

PMID- 24940113
TI  - Metastatic renal cell carcinoma without evidence of a primary renal tumour.
AB  - Although metastases are common in patients with renal cell carcinoma (rcc), it is
      extremely rare for patients to present with metastatic rcc (mrcc) without
      evidence of a primary mass in the kidney. Two cases of mrcc with no detectable
      primary renal mass are reported here. Both patients had bilateral native kidneys
      in situ and no significant prior urologic history. The first patient presented
      with a hip fracture and was found to have multiple radiologic bony and lung
      metastases. Biopsy of a mass involving the pubic bone demonstrated clear cell
      mrcc. Multiple scans by computed tomography (ct) and confirmatory imaging by
      magnetic resonance demonstrated no renal mass. This first patient had disease
      stabilization for 18 months on sunitinib and was still alive at last follow-up.
      The second patient was diagnosed with clear-cell mrcc after thickened synovium
      was discovered and biopsied during a knee arthroplasty. Multiple scans by ct in
      this second patient demonstrated no primary renal mass. Sunitinib and
      radiotherapy to the knee lesion were initiated, but unfortunately, the patient
      deteriorated clinically and passed away from disease progression shortly after
      diagnosis. Because of the rare nature of these cases, a standardized course of
      action has not yet been established. However, we hypothesize that it is
      reasonable to manage metastases in these patients by following established mrcc
      protocols. 

PMID- 24940114
TI  - Truth be told-perspectives on openness.

PMID- 24940117
TI  - From the Editor's Desk.

PMID- 24940115
TI  - Perioperative hypoxemia is common with horizontal positioning during general
      anesthesia and is associated with major adverse outcomes: a retrospective study
      of consecutive patients.
AB  - BACKGROUND: Reported perioperative pulmonary aspiration (POPA) rates have
      substantial variation. Perioperative hypoxemia (POH), a manifestation of POPA,
      has been infrequently studied beyond the PACU, for patients undergoing a diverse
      array of surgical procedures. METHODS: Consecutive adult patients with ASA I-IV
      and pre-operative pulmonary stability who underwent a surgical procedure
      requiring general anesthesia were investigated. Using pulse oximetry, POH was
      documented in the operating room and during the 48 hours following PACU
      discharge. POPA was the presence of an acute pulmonary infiltrate with POH.
      RESULTS: The 500 consecutive, eligible patients had operative body-positions of
      prone 13%, decubitus 8%, sitting 1%, and supine/lithotomy 78%, with standard
      practice of horizontal recumbency. POH was found in 150 (30%) patients. Post
      operative stay with POH was 3.7 +/- 4.7 days and without POH was 1.7 +/- 2.3 days
      (p < 0.0001). POH rate varied from 14% to 58% among 11 of 12 operative procedure
      categories. Conditions independently associated with POH (p < 0.05) were acute
      trauma, BMI, ASA level, glycopyrrolate administration, and duration of surgery.
      POPA occurred in 24 (4.8%) patients with higher mortality (8.3%), when compared
      to no POPA (0.2%; p = 0.0065). Post-operative stay was greater with POPA (7.7 +/-
      5.7 days), when compared to no POPA (2.0 +/- 2.9 days; p = 0.0001). Conditions
      independently associated with POPA (p < 0.05) were cranial procedure, ASA level,
      and duration of surgery. POPA, acute trauma, duration of surgery, and inability
      to extubate in the OR were independently associated with post-operative stay (p <
      0.05). POH, gastric dysmotility, acute trauma, cranial procedure, emergency
      procedure, and duration of surgery had independent correlations with post
      operative length of stay (p < 0.05). CONCLUSIONS: Adult surgical patients
      undergoing general anesthesia with horizontal recumbency have substantial POH and
      POPA rates. Hospital mortality was greater with POPA and post-operative stay was
      increased for POH and POPA. POH rates were noteworthy for virtually all
      categories of operative procedures and POH and POPA were independent predictors
      of post-operative length of stay. A study is needed to determine if modest
      reverse-Trendelenburg positioning during general anesthesia has a relationship
      with reduced POH and POPA rates.

PMID- 24940118
TI  - Advancing evidence-based practice - a quarterly compilation of research updates
      most likely to change clinical practice.

PMID- 24940116
TI  - Autologous anti-SOX2 antibody responses reflect intensity but not frequency of
      antigen expression in small cell lung cancer.
AB  - BACKGROUND: Anti-SOX2 antibody responses are observed in about 10 to 20% of small
      cell lung cancer (SCLC) patients. The aim of this study was to determine whether
      such responses reflect a particular pattern of SOX2 protein expression in the
      tumor and whether this pattern associates with clinical outcome. METHODS:
      Paraffin embedded tumor tissues, obtained from SCLC patients who had no evidence
      of paraneoplastic autoimmune degeneration, were evaluated for SOX2 expression by
      immunohistochemistry for both intensity and extent of staining. Sera from the
      same patients were tested for autologous antibodies against recombinant SOX2 by
      enzyme-linked immunosorbent assay (ELISA). Correlates between overall survival
      and various clinical parameters including SOX2 staining and serology were
      determined. RESULTS: SOX2 protein expression was observed in tumor tissue in 89%
      of patients. Seventeen patients (29%) were seropositive for SOX2 antibodies and,
      in contrast to SOX2 staining, the presence of antibody correlated with limited
      disease stage (p = 0.05). SOX2 seropositivity showed a significant association
      with the intensity of SOX2 staining in the tumor (p = 0.02) but not with the
      frequency of SOX2 expressing cells. CONCLUSION: Anti-SOX2 antibodies associate
      with better prognosis (limited stage disease) while SOX2 protein expression does
      not; similar to reports from some earlier studies. Our data provides an
      explanation for this seemingly contrasting data for the first time as SOX2
      antibodies can be observed in patients whose tumors contain relatively few but
      strongly staining cells, thus supporting the possible presence of active immune
      surveillance and immune-editing targeting SOX2 protein in this tumor type.

PMID- 24940119
TI  - Bioethics in practice - a quarterly column about medical ethics: ethics and end
      stage renal disease.

PMID- 24940120
TI  - Clinical images - a quarterly column: actively rupturing intracranial aneurysm.

PMID- 24940121
TI  - Editorial - the importance of mentors.

PMID- 24940122
TI  - Editorial - the transition to the international classification of diseases-10 for
      physician services.

PMID- 24940123
TI  - Editorial - My Boston Family's New Orleans Connection.

PMID- 24940124
TI  - Combination immunotherapy for high-risk resected and metastatic melanoma
      patients.
AB  - BACKGROUND: Patients with advanced melanoma have a poor outcome. We hypothesize
      that combination immunotherapy can synergistically activate host immunity to
      generate an effective treatment for patients with high-risk, resected stage 3,
      recurrent, refractory, or stage 4 melanoma. METHODS: We conducted a phase 2
      clinical trial of HyperAcute Melanoma (HAM) vaccine (NLG-12036, NewLink Genetics)
      combined with pegylated interferon (Sylatron, Merck). Trial design consisted of a
      12-week regimen with the initial 4 weekly treatments consisting of HAM alone
      (intradermally) followed by 8 additional treatments of HAM plus Sylatron
      (subcutaneously, 6 MUg/kg). Trial endpoint outcomes include clinical response,
      overall safety, and correlative findings for observed antitumor effect. RESULTS:
      Our cohort consisted of 25 patients with a median age of 60. Twenty-one patients
      completed the trial and 4 stopped because of progressive disease (PD). According
      to the Response Evaluation Criteria in Solid Tumors, of the 16 stage 4 patients,
      2 had a complete response (CR), 1 had stable disease, and 4 had no evidence of
      disease (NED) after resection. For stage 2/3 patients, 3 of 9 remained NED, and
      the 1 stage 2C patient had slow PD with a single site resected and is currently
      NED. The median overall survival time was 29 months, with 60% of the patients
      surviving for >1 year. Of the 25 patients, 12 (48%) are still alive. All
      evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Four
      of 25 patients developed vitiligo, correlating with 2 CR patients and 2 NED
      patients. CONCLUSION: Combination immunotherapy with HAM plus Sylatron shows
      clinical efficacy with tumor regression and concomitant immune activation.
      Optimization of dosing schedules and therapeutic efficacy should be further
      explored to enhance the benefit of this promising immunotherapeutic approach.

PMID- 24940125
TI  - Intraoperative and Postoperative Blood Glucose Concentrations in Diabetic
      Surgical Patients Receiving Lactated Ringer's Versus Normal Saline: A
      Retrospective Review of Medical Records.
AB  - BACKGROUND: Hyperglycemia is associated with poor postoperative outcomes after
      carotid endarterectomy. This retrospective study examined the effect of lactated
      Ringer's and normal saline solutions on intraoperative blood glucose control in
      diabetic patients undergoing carotid endarterectomy. METHODS: The anesthetic and
      surgical records of type 2 diabetic patients who underwent carotid endarterectomy
      and received either lactated Ringer's solution or normal saline exclusively
      during the case were reviewed, and 20 patients were randomly selected from each
      group for further analysis. The outcome of interest was preoperative to
      postoperative change in blood glucose. RESULTS: The preoperative to postoperative
      mean changes in glucose for the normal saline and lactated Ringer's groups were
      34.4 +/- 70.32 mg/dL and 64.5 +/- 61.38 mg/dL, respectively. This slight
      difference in the mean change in glucose between the 2 groups was not
      statistically significant (P=0.157). CONCLUSION: Lactated Ringer's solution does
      not appear to cause a significant change in the mean blood glucose levels in
      diabetic patients undergoing carotid endarterectomy compared to patients
      receiving normal saline. Randomized controlled trials are needed to further
      determine whether lactated Ringer's solution adversely affects glucose control in
      diabetic surgical patients.

PMID- 24940126
TI  - Postoperative vision loss after spine surgery: a single-institution case-control
      comparison.
AB  - BACKGROUND: Postoperative vision loss (POVL) after spine surgery is a rare but
      devastating outcome. We present the first case-control study from a single
      institution for POVL with the diagnoses of ischemic optic neuropathy or central
      vision loss after complex spine surgery. METHODS: POVL cases following spine
      surgeries between December 1995 and December 2010 at the Cleveland Clinic were
      identified retrospectively using administrative codes. Each instance of POVL was
      matched to 5 case-control patients based on age, gender, body mass index,
      systolic blood pressure, diastolic blood pressure, mean arterial pressure, and
      hematocrit. Duration of anesthesia, fluid volumes, and hemodynamic measurements
      were then compared between POVL cases and control cases using Wilcoxon rank sum
      test. RESULTS: Six patients developed POVL. These patients had significantly
      greater blood loss (P=0.002, Wilcoxon test) and a significantly greater volume of
      red blood cells transfused (P=0.006) than the control patients. No other
      intraoperative measures differed significantly after Bonferroni correction for
      multiple outcomes. CONCLUSION: We found that patients with POVL had significantly
      greater blood loss and significantly more red blood cell transfusions than their
      matched controls.

PMID- 24940127
TI  - Lund-mackay staging system in cystic fibrosis: a prognostic factor for revision
      surgery?
AB  - BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive genetic disease that
      affects approximately 30,000 people in the United States. Mucus in CF patients
      can be exceptionally viscous, leading to progressive cycles of inflammation and
      infection. The most widely accepted staging system used to score sinus computed
      tomography (CT) scans is the Lund-Mackay Score (LMS). METHODS: To determine if a
      significant correlation exists between LMS and the need for revision sinus
      surgery in a patient population with CF, we performed a retrospective review of
      32 patients with CF who were referred to the Tulane Otolaryngology Clinic from
      2005 to 2011 and received a CT scan of the paranasal sinuses. CT scans were
      graded in a blinded manner by the institution's neuroradiologist using the LMS
      system. RESULTS: We found no statistically significant difference in the raw or
      scaled LMSs between patients receiving revision surgery (n=9) and patients
      receiving a single surgery (n=23). CONCLUSIONS: CT scans are vital for
      preoperative planning, but they are not a useful tool for risk stratification.
      More specifically, application of the LMS is not relevant in identifying which CF
      patients with chronic rhinosinusitis will be at risk for revision surgeries.

PMID- 24940128
TI  - Intracranial subdural empyema: a 10-year case series.
AB  - BACKGROUND: Intracranial subdural empyema (ISDE) is a pyogenic infection located
      in the space between the dura and arachnoid mater. Early diagnosis, prompt
      initiation of antimicrobial therapy, and surgical drainage are essential to
      reduce morbidity and mortality. This case series analyzes the presentation and
      management of ISDE in Queensland, Australia, over a 10-year period. METHODS:
      Thirty-six patients with ISDE were treated at Gold Coast University Hospital,
      Princess Alexandra Hospital, Townsville Hospital, and Royal Brisbane Hospital.
      The patients' medical records were analyzed to ascertain patient demographics,
      etiology, presentation, and management. RESULTS: A slight male preponderance
      occurred in the cohort of 36 patients with ISDE. The most common source of
      infection was a neurosurgical procedure, followed by sinusitis and otogenic
      sources. Headache, fever, and altered sensorium were the most common clinical
      triad of symptoms, present in 19 (53%) patients. Craniotomy was performed as the
      initial surgical procedure in 28 (88%) of the 32 patients who required surgery.
      Seizure prophylaxis was given to 25 (69%) patients, with 8 (32%) of those
      patients having seizures during their hospitalizations despite this therapy. Five
      (14%) patients required readmission and a second craniotomy because of failed
      resolution of the ISDE. CONCLUSION: Altered sensorium, fever, vomiting, and
      headache should alert the clinician to the possibility of ISDE. A history of
      neurosurgery, sinusitis, otitis media, or skull trauma increases the likelihood
      of this differential. Management includes sensitive antibiotic therapy and
      surgical drainage. Compared with burr hole, craniotomy is associated with less
      recurrence of ISDE.

PMID- 24940129
TI  - Clinical decision support alert appropriateness: a review and proposal for
      improvement.
AB  - BACKGROUND: Many healthcare providers are adopting clinical decision support
      (CDS) systems to improve patient safety and meet meaningful use requirements.
      Computerized alerts that prompt clinicians about drug-allergy, drug-drug, and
      drug-disease warnings or provide dosing guidance are most commonly implemented.
      Alert overrides, which occur when clinicians do not follow the guidance presented
      by the alert, can hinder improved patient outcomes. METHODS: We present a review
      of CDS alerts and describe a proposal to develop novel methods for evaluating and
      improving CDS alerts that builds upon traditional informatics approaches. Our
      proposal incorporates previously described models for predicting alert overrides
      that utilize retrospective chart review to determine which alerts are clinically
      relevant and which overrides are justifiable. RESULTS: Despite increasing
      implementations of CDS alerts, detailed evaluations rarely occur because of the
      extensive labor involved in manual chart reviews to determine alert and response
      appropriateness. Further, most studies have solely evaluated alert overrides that
      are appropriate or justifiable. Our proposal expands the use of web-based
      monitoring tools with an interactive dashboard for evaluating CDS alert and
      response appropriateness that incorporates the predictive models. The dashboard
      provides 2 views, an alert detail view and a patient detail view, to provide a
      full history of alerts and help put the patient's events in context. CONCLUSION:
      The proposed research introduces several innovations to address the challenges
      and gaps in alert evaluations. This research can transform alert evaluation
      processes across healthcare settings, leading to improved CDS, reduced alert
      fatigue, and increased patient safety.

PMID- 24940130
TI  - Steroids: pharmacology, complications, and practice delivery issues.
AB  - BACKGROUND: Since their identification nearly 80 years ago, steroids have played
      a prominent role in the treatment of many disease states. Many of the clinical
      roles of steroids are related to their potent antiinflammatory and immune
      modulating properties. METHODS: This review summarizes the basic pharmacology,
      complications, and practice delivery issues regarding steroids. RESULTS:
      Clinically relevant side effects of steroids are common and problematic. Side
      effects can occur at a wide range of doses and vary depending on the route of
      administration. The full spectrum of side effects can be present even in patients
      taking low doses. CONCLUSIONS: Practitioners must be aware that these drugs might
      exacerbate a preexisting condition or present a new medical condition. Knowledge
      of the clinical implications of prescribing these agents is critical.

PMID- 24940131
TI  - Availability and utilization of opioids for pain management: global issues.
AB  - BACKGROUND: Pain can significantly influence an individual's health status and
      can have serious negative consequences: poor nutrition, decreased appetite,
      abnormal sleep patterns, fatigue, and impairment of daily living activities. Pain
      can cause psychological impairment and decrease healing and recovery from
      injuries and illness. A hallmark of many chronic conditions, pain affects more
      patients' lives than diabetes mellitus, heart disease, and cancer combined.
      However, many chronic sufferers do not have access to effective pain management
      for a variety of reasons, including limited access, restrictions, and personal
      and cultural biases. METHODS: This review summarizes issues of access,
      distribution, and cultural bias with regard to opioid agents and seeks to clarify
      the challenges related to opioid delivery. The considerable negative physical and
      mental consequences of chronic pain are discussed for the general and palliative
      care population. RESULTS: Opioids are an effective treatment for various
      intractable painful conditions, but problems in global opioid access for safe and
      rational use in pain management contribute to unnecessary suffering. These
      problems persist despite increased understanding in recent years of the
      pathophysiology of pain. CONCLUSIONS: Comprehensive guidelines for goal-directed
      and patient-friendly chronic opiate therapy will potentially enhance the outlook
      for future chronic pain management. The improvement of pain education in
      undergraduate and postgraduate training will benefit patients and clinicians. The
      promise of new medications, along with the utilization of multimodal approaches,
      has the potential to provide effective pain relief to future generations of
      sufferers.

PMID- 24940133
TI  - Tuberous sclerosis complex: perioperative considerations.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC), also known as Bourneville disease,
      is an inherited, progressive neurocutaneous disorder characterized by the
      potential for hamartoma formation throughout the body. TSC is an autosomal
      dominant genetic disorder, but more than two-thirds of cases are sporadic.
      METHODS: Clinical manifestations and treatment options are discussed. Both
      surgical and anesthetic perioperative considerations are described in this
      review. RESULTS: Routine monitoring is appropriate for minor surgical procedures
      for patients with TSC who have mild disease manifestations. More extensive
      monitoring is indicated for major procedures that have the potential for
      significant blood loss and for patients with more severe pathology.
      Postoperatively, TSC patients should be admitted for monitoring and treatment
      after more extensive procedures or if significant organ dysfunction occurs.
      Postoperative complications, which may be related to either the surgery or the
      TSC pathology itself, may have origins in many different organs and may include
      seizures, severe hypertension, and bradyarrhythmias. CONCLUSION: TSC is a rare
      disease with a highly variable clinical presentation and provides a multitude of
      challenges for the patient, the family, and the healthcare team.

PMID- 24940132
TI  - Effect of opiates, anesthetic techniques, and other perioperative factors on
      surgical cancer patients.
AB  - BACKGROUND: Opioid pharmacotherapy is often used to treat cancer pain. However,
      morphine and other opioid-like substance use in patients with cancer may have
      significant adverse consequences, including the suppression of both innate and
      acquired immune responses. Although studies have examined the possibility that
      regional anesthesia attenuates the immunosuppressive response of surgery, the
      effects of morphine and other opioid-related substances on tumor progression
      remain unknown. METHODS: This article presents an evidence-based review of the
      influence of opioids and anesthetic technique on the immune system in the context
      of cancer recurrence. The review focuses on the field of regional anesthesia and
      the setting of surgical oncologic procedures. The method for perioperative pain
      management and the technique of anesthesia chosen for patients in cancer surgery
      were explored. RESULTS: General anesthetics have been indicated to suppress both
      cell-mediated immunity and humoral immunity. Evidence suggests that intravenous
      opioids suppress the immune system. However, the mechanisms by which anesthetics
      and analgesics inhibit the immune system are not understood. Compared with the
      alternatives, regional analgesia offers reduced blood loss and superior
      postoperative analgesia. Because of these advantages, the use of regional
      analgesia has increased in oncologic surgeries. CONCLUSION: Immune responses from
      all components of the immune system, including both the humoral and cell-mediated
      components, appear to be suppressed by anesthetics and analgesics. The clinical
      anesthesiologist should consider these factors in the application of technique,
      especially in cancer surgery.

PMID- 24940134
TI  - Spontaneous epidural air entrapment.
AB  - BACKGROUND: Epidural pneumorrhachis (EPR), an extension of pneumomediastinum,
      results from air that leaks from the mediastinum and accumulates in the epidural
      space of the spine. It is an uncommon, benign condition; most cases are
      asymptomatic, are recognized only on computed tomography scans, and require no
      treatment. CASE REPORT: We present a case of EPR, pneumomediastinum,
      pneumothorax, and subcutaneous emphysema in a young male who was managed
      conservatively with supportive care. CONCLUSIONS: EPR is a rare yet benign
      condition that can be found incidentally while working up lung or spine
      pathology. Although radiography can define the presence of a pneumomediastinum
      and subcutaneous emphysema, the diagnosis of EPR can only be made using computed
      tomography. The management of EPR is usually conservative, and the focus should
      be on underlying disease.

PMID- 24940136
TI  - Atrial fibrillation and acute respiratory failure: unique presentation of diffuse
      large B-cell lymphoma.
AB  - BACKGROUND: Diffuse large B-cell lymphoma is the most common lymphoid neoplasm,
      accounting for approximately 25% of all non-Hodgkin lymphomas. Patients typically
      present with nodal enlargement, fever, weight loss, or night sweats. Extranodal
      extramedullary disease occurs in up to 40% of cases with the most common site of
      extranodal involvement being the gastrointestinal tract. However, diffuse large B
      cell lymphoma can present in virtually any area, including the testes, bones,
      thyroid, salivary glands, tonsils, skin, liver, breasts, adrenals, kidneys, nasal
      cavity, paranasal sinuses, cervix, and central nervous system. CASE REPORT: We
      present a unique case of atrial fibrillation and respiratory failure as an
      initial presentation of diffuse large B-cell lymphoma with cardiac and cavitary
      pulmonary involvement. CONCLUSION: The recent advances in chemotherapeutic
      options allow for and reinforce the importance of tailoring the chemotherapy
      regimen to the individual patient's unique presentation. In our patient,
      presentation included extensive intracardiac involvement resulting in
      arrhythmias, cavitary pulmonary nodules, and acute hypoxemic respiratory failure
      requiring ventilator support.

PMID- 24940135
TI  - High-degree atrioventricular block in a child with acute myocarditis.
AB  - BACKGROUND: Viral myocarditis is a common cause of transient electrocardiogram
      (EKG) abnormalities in children. The clinical presentation of acute myocarditis
      ranges from asymptomatic infection to fulminant heart failure and sudden death.
      Many children present with nonspecific symptoms such as dyspnea or vomiting,
      frequently leading to misdiagnosis. EKG abnormalities are a sensitive indicator
      of acute myocarditis and are present in more than 90% of cases. CASE REPORT: A 13
      year-old female suffered a syncopal episode and was found to have high-grade
      atrioventricular (AV) block caused by acute presumed viral myocarditis. With
      close monitoring, the EKG abnormalities resolved over the following 48 hours. In
      this case report, we discuss the incidence, pathogenesis, and outcomes of
      conduction disturbances in acute myocarditis. CONCLUSION: High-degree AV block
      can occur in patients with acute myocarditis, and higher-degree AV block is
      correlated with greater myocardial injury. Additionally, severity of pathological
      changes may reflect the reversibility of AV block. In the majority of cases,
      however, this rhythm disturbance is transient and does not require permanent
      pacemaker placement.

PMID- 24940138
TI  - Analgesic efficacy and technique of ultrasound-guided suprascapular nerve
      catheters after shoulder arthroscopy.
AB  - BACKGROUND: Conventional approaches to brachial plexus blocks may not cover the
      suprascapular nerve. Accordingly, after shoulder arthroscopy, sensation from the
      posterior part of the shoulder is commonly spared. Most previous research
      involving suprascapular nerve blocks described single-injection techniques.
      However, with the widespread availability and fairly reasonable cost of
      disposable infusion pumps, continuous catheter techniques provide a more
      appealing method of prolonging postoperative analgesia. CASE REPORT: We describe
      2 patients who were successfully treated with ultrasound-guided continuous
      suprascapular nerve catheters. With the patient seated, a high-frequency linear
      ultrasound probe was used. Both patients experienced excellent pain relief
      without complications. CONCLUSION: Continuous suprascapular catheter techniques
      provide good pain relief and improve postoperative analgesia after shoulder
      arthroscopy.

PMID- 24940137
TI  - Two Cases of Fulminant Hepatic Failure from Amanita phalloides Poisoning Treated
      Additively by Homeopathy.
AB  - BACKGROUND: Intoxication with Amanita phalloides is associated with high
      morbidity and mortality. Treatment therapies include general support, toxin
      elimination, pharmacotherapy with agents such as the hepatoprotective agent
      silibinin, and, in extreme states, liver transplantation. Despite these
      therapeutic interventions, mortality remains relatively high. CASE REPORTS: We
      present reports of 2 patients with severe hepatic failure following intoxication
      with Amanita phalloides. Both patients were admitted to the intensive care unit;
      1 patient suffered from hepatic failure solely, and the second patient
      experienced severe 5-organ failure. In addition to conventional intensive care
      treatment, both patients were treated additively with classical homeopathy. The 2
      patients survived without any residual pathological sequelae. CONCLUSION: Based
      on the 2 cases, including 1 extreme situation, we suggest that adjunctive
      homeopathic treatment has a role in the treatment of acute Amanita phalloides
      induced toxicity following mushroom poisoning. Additional studies may clarify a
      more precise dosing regimen, standardization, and better acceptance of
      homeopathic medicine in the intensive care setting.

PMID- 24940139
TI  - Early recognition and management of laryngeal fracture: a case report.
AB  - BACKGROUND: Laryngeal fracture is a rare condition that can lead to significant
      problems with airway patency, voice production, and swallowing. Conflict in the
      literature exists regarding the most suitable way to manage this injury. CASE
      REPORT: We present the case of a 29-year-old Caucasian man who sustained a
      displaced fracture of the thyroid cartilage due to blunt trauma. He reported no
      swallowing, breathing, or voice problems after 1 year, and his recovery can be
      attributed to the early recognition and proper management of his condition.
      CONCLUSION: This case illustrates the importance of ensuring a high level of
      suspicion for laryngeal fracture in the acute trauma patient. Early
      identification of this injury allows early intervention that not only protects
      the airway but also improves long-term voice and airway outcomes.

PMID- 24940140
TI  - Successful lung transplantation from a donor with persistent lobar atelectasis.
AB  - BACKGROUND: Over the past 15 years, the number of recipients waiting for a lung
      transplant has increased and now far exceeds the number of available donors.
      Liberalization of donor criteria to include the use of extended donors remains an
      attractive option for expanding the donor pool. Numerous centers, including the
      authors' own, have begun exploring this relatively unknown territory of lung
      transplantation. CASE REPORT: Successful bilateral lung transplantation was
      performed for a patient with emphysema utilizing lungs from a donor with
      persistent lobar atelectasis. CONCLUSION: This report demonstrates that an
      acceptable outcome is possible from a donor with persistent lobar atelectasis if
      other parameters are acceptable. Larger studies would help further our
      understanding of the impact of donor radiographic abnormalities on outcomes
      following lung transplantation.

PMID- 24940142
TI  - Chorea in a chronic pain patient using gabapentin.
AB  - BACKGROUND: Gabapentin increasingly is being used to treat chronic pain in
      addition to seizures, anxiety, and bipolar disorder. Chorea has been reported as
      a potential side effect of gabapentin. CASE REPORT: We report the case of a
      patient with chronic low back pain who was treated with a host of modalities,
      including gabapentin. After she increased her dose of gabapentin, she developed
      chorea of the upper extremities, neck, and head. With cessation of gabapentin,
      the bulk of her symptoms resolved within 24 hours, and symptoms completely
      resolved in the following months. CONCLUSIONS: Chorea is thought to appear when
      the basal ganglia are deregulated. Gabapentin interferes with gamma-aminobutyric
      acid, the primary inhibitory neurotransmitter in the motor pathway. Chorea
      associated with gabapentin has been reported in several case studies, but not at
      a dose as low as the patient took in this case.

PMID- 24940141
TI  - Renal medullary carcinoma: a case report and brief review of the literature.
AB  - BACKGROUND: Renal medullary carcinoma (RMC) is an aggressive form of non-clear
      cell kidney cancer that typically affects young adults and is almost exclusively
      associated with sickle cell trait. Typical RMC patients tend to be young black
      males (2:1 male to female predominance) with sickle cell trait who present with
      pain and hematuria and are found to have metastatic disease at diagnosis.
      Prognosis is extremely poor, with a mean survival of less than a year in most
      cases. CASE REPORT: We present a case illustrative of many of the classic
      findings of RMC. A 25-year-old female with a past medical history of sickle cell
      trait presented to the emergency room with right-sided flank pain. Initially, a
      computed tomography (CT) scan showed only a benign-appearing cystic lesion 4.5 cm
      in diameter in the right kidney. Six months later, the patient re-presented with
      hematuria, lightheadedness, and dizziness. A repeat CT scan showed that the renal
      cyst had enlarged to 5.6 cm. The patient underwent a decortication and
      fulguration procedure that revealed malignancy in the wall of the cyst. She was
      given a series of treatments but experienced progressive disease and passed away
      2 years and 8 months after metastatic diagnosis. CONCLUSION: Neither systemic
      therapy nor radiation therapy has been found to be particularly efficacious in
      the treatment of RMC. As the underlying biologic mechanisms of RMC are further
      elucidated on a basic science level, we expect new translational research
      opportunities will emerge and novel treatment options will be developed for this
      rare and dismal disease.

PMID- 24940143
TI  - Endobronchial ultrasound in a patient with right aortic arch.
AB  - BACKGROUND: A right-sided aortic arch (RAA) is a rare anomaly of the
      cardiovascular system, presenting in only 0.1% of the population. In some
      reported cases, RAA is accompanied by another cyanotic vascular anomaly such as
      tetralogy of Fallot, and patients with such anomalies are usually diagnosed in
      fetal life or early childhood. Most patients are asymptomatic if the RAA presents
      individually. CASE REPORT: We report the case of a 27-year-old African American
      man who presented to urgent care with 3 weeks of progressive dry cough with mild
      shortness of breath, low-grade fevers, and night sweats. He was not on any
      medication. Radiographic examination of the chest showed a right paratracheal
      mass displacing the trachea to the left, suggesting a vascular anomaly with
      mediastinal adenopathy. Radiographic images suggested either lymphoma or chronic
      granulomatous disease, and the patient underwent endobronchial ultrasound
      bronchoscopy under general anesthesia. He was ultimately diagnosed with
      sarcoidosis. CONCLUSION: Endobronchial ultrasound with real-time guided
      transbronchial needle aspiration played a significant role in obtaining a
      sufficient tissue sample to make the diagnosis with minimal side effects, despite
      the presence of the RAA anomaly.

PMID- 24940144
TI  - Primary amyloidosis of the breast presenting as a solitary nodule: case report
      and review of the literature.
AB  - BACKGROUND: Amyloidosis of the breast is an unusual diagnosis. Overall, only 2
      major case series have been published in the literature since the time
      amyloidosis was first reported in 1973, highlighting the rare nature of this
      disease. Clinically, the patient may present with a breast mass or simply
      increased breast density and skin thickening. As such, amyloidosis may mimic the
      appearance of a number of pathologies, both benign and malignant. CASE REPORT: We
      report a single case of a patient who presented with a breast mass and was
      ultimately diagnosed with primary amyloidosis of the breast. We also present a
      review of the literature to date. CONCLUSION: The main treatment for primary
      amyloidosis of the breast is surgical removal, most often accomplished with
      breast conservation via lumpectomy. In performing the lumpectomy, the goal should
      be to obtain negative surgical margins; however, no strong data exist to suggest
      that such lesions would recur with a microscopically positive margin.

PMID- 24940145
TI  - Anomalous right coronary artery: a case report.
AB  - BACKGROUND: Anomalous coronary arteries (ACAs) are rare but potentially life
      threatening abnormalities of coronary circulation. Most variations are benign;
      however, some may lead to myocardial ischemia and/or sudden cardiac arrest. CASE
      REPORT: We present the case of a patient with a significant medical history of
      hypertension, hyperlipidemia, type 2 diabetes, obesity, and gastroesophageal
      reflux disease who presented to the emergency department with atypical chest
      pain. She underwent a cardiac catheterization that showed an anomalous right
      coronary artery originating near the anterior left coronary artery sinus and
      coursing between the pulmonary artery and aorta. The patient was deemed a poor
      surgical candidate, was discharged home on medical management with beta blocker
      therapy, and was instructed to restrict her physical activity. CONCLUSION:
      Treatment of significant anomalies should be guided by the nature of the
      anomalous vessel. Symptomatic patients with ACAs have 3 treatment options:
      medical management, coronary angioplasty and stent deployment, or surgical
      correction. These treatment options remain controversial. Some clinicians
      advocate revascularization, but the long-term benefits of revascularization
      therapies have not yet been demonstrated.

PMID- 24940146
TI  - Pemetrexed and communicating hydrocephalus.
AB  - BACKGROUND: Pemetrexed (Alimta) is widely used in combination with platinum as a
      first-line treatment of mesothelioma and adenocarcinoma of the lung. It is also
      approved for use in the maintenance setting as a single agent after patient
      completion of 4 to 6 cycles of a platinum-based doublet regimen for non-small
      cell lung cancer. With the increasing use of pemetrexed and longer durations of
      therapy, unexpected cumulative toxicity or other toxicities are possible. CASE
      REPORT: We report a case of a patient receiving maintenance pemetrexed for
      advanced adenocarcinoma of the lung who developed communicating hydrocephalus.
      CONCLUSION: We are not aware of any other reports of communicating hydrocephalus
      in association with pemetrexed therapy. As more patients routinely receive
      pemetrexed as maintenance therapy, the development of toxicities or unexpected
      diagnoses is possible and may be a consideration in the chronic management of
      such patients.

PMID- 24940147
TI  - Cytomegalovirus hepatitis and pancreatitis in the immunocompetent.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a double-stranded DNA virus and a member of
      the Herpesviridae family. It is a lytic virus that causes a cytopathic effect in
      vitro and in vivo. CMV affects nearly all humans, with a 60%-100% seroprevalence
      worldwide, and in the immunocompetent it typically manifests as a mild and self
      limiting mononucleosis syndrome. In immunocompromised patients, CMV has the
      ability to cause significant inflammation in many different organ systems. CASE
      REPORT: We report an unusual case of hepatitis and pancreatitis secondary to CMV
      in an immunocompetent patient. A 29-year-old male was admitted with elevated
      lipase, elevated aminotransferases, and epigastric pain after an acute viral
      prodrome. An initial CMV DNA polymerase chain reaction workup was positive,
      indicating acute or reactivated infection. Liver histology was consistent with
      CMV infection. Magnetic resonance cholangiopancreatography, endoscopic
      ultrasound, and intraoperative cholangiogram were not indicative of other
      etiologies. CMV viremia was successfully cleared with ganciclovir, and the
      patient experienced clinical and biochemical improvements. CONCLUSION:
      Pancreatitis and hepatitis secondary to CMV are rare but should be considered in
      the workup of immunocompetent patients, especially in the presence of a recent
      viral-like illness.

PMID- 24940148
TI  - Letters to the editor.

PMID- 24940150
TI  - CME Upcoming Events.

PMID- 24940151
TI  - Advanced Imaging Techniques in the Diagnosis of Nonlesional Epilepsy: MRI, MRS,
      PET, and SPECT.
AB  - Once patients have a diagnosis of localization related epilepsy (LRE), it is
      critical to further classify those patients into lesional or nonlesional for
      treatment and prognostic reasons. An individual with LRE may be classified as
      nonlesional for two reasons: 1) a lesion may not exist; that is, the structural
      abnormality that gives rise to seizures may be at the channel level or be
      spatially distributed in such a way that it would not be accurately termed a
      lesion, or 2) a lesion exists but is so subtle that standard clinical imaging is
      not sensitive enough to discriminate between the lesion and surrounding healthy
      brain tissue. As with any technology and disease process, this definition is
      dynamic, as we know that future imaging techniques will be developed and new
      disease mechanisms will be discovered, making detection of the epileptogenic
      underlying abnormality an ever-changing target. 

PMID- 24940152
TI  - Antiepileptic drugs and suicide: the light at the end of the tunnel.

PMID- 24940149
TI  - Recent publications by ochsner authors: october 2013 - march 2014.

PMID- 24940153
TI  - Paradox Lost: Exploring the Clinical-Radiologic Dissociation Seen in Anti-NMDA
      Receptor Encephalitis.

PMID- 24940154
TI  - Complex detection, complex decisions: more detail on subclinical seizures in the
      acutely sick brain.

PMID- 24940155
TI  - Moving Beyond Ruling Out Epilepsy: It Is PNES!

PMID- 24940156
TI  - Why Hemispheric Lateralization of Language is Only Part of the Story in Epilepsy
      Surgery Candidates.

PMID- 24940157
TI  - P-glycoprotein Expression and Pharmacoresistant Epilepsy: Cause or Consequence?

PMID- 24940158
TI  - Finally, a flood of fascinating facts and findings on final outcomes after
      frontal lobe epilepsy surgery.

PMID- 24940159
TI  - Treating epilepsy in tuberous sclerosis with everolimus: getting closer.

PMID- 24940160
TI  - Improving patient-centered care coordination for children with epilepsy: version
      2.0 upgrade required.

PMID- 24940161
TI  - Hope for new treatments for acute repetitive seizures.

PMID- 24940162
TI  - Juvenile myoclonic epilepsy-what does the future look like?

PMID- 24940163
TI  - What the dentate gyrus and the millennial in your basement have in common.

PMID- 24940164
TI  - When GABA Fails: Rundown on Chemokines.

PMID- 24940165
TI  - Toward routine genetics-based diagnoses for the epileptic encephalopathies.

PMID- 24940166
TI  - Absence Epilepsy: The Tail WAGs the Rat.

PMID- 24940167
TI  - Stopping epileptogenesis dead in its trks.

PMID- 24940168
TI  - Sleep problems and associated factors in children with juvenile idiopathic
      arthritis: a systematic review.
AB  - BACKGROUND: Sleep problems are common among children with chronic illnesses such
      as Juvenile Idiopathic Arthritis (or JIA). However, little is known about the
      frequency and severity of sleep disturbance(s) and the factors that are
      associated with sleep problems in children with JIA. The mechanism(s) of the
      relationships characterizing the development or exacerbation of sleep problems in
      children with JIA are still unknown, however studies have reported an
      association. The purpose of this study was to synthesize existing research
      related to sleep problems in children with JIA. METHODS: The Preferred Reporting
      Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the
      conduct and reporting of this review. An experienced librarian conducted searches
      in MEDLINE, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of
      Controlled Trials from inception to January 2012, to identify potentially
      relevant citations. Two members independently selected, rated methodological
      quality using the QUIPS tool, and extracted data from included studies. RESULTS:
      Ten studies were included and findings varied across studies; studies were mostly
      cross-sectional, or case-controlled designs, with only one cohort study
      available. Four studies found that children and adolescents diagnosed with JIA
      had significantly more sleep disturbances when compared to healthy controls. Pain
      was most often associated with sleep disturbances. The heterogeneous findings
      highlight the complex relationships between JIA and sleep, and low methodological
      quality of studies in the field. CONCLUSIONS: This review supports an association
      between poor sleep and increased symptoms related to JIA, specifically the
      experience of pain. However, results need to be interpreted cautiously given the
      inconsistent findings regarding factors associated with sleep problems in JIA,
      the limited evidence available, and its low quality. Furthermore it is not yet
      determined if the poor sleep patterns predate the symptoms reported with JIA.
      More research is vital to understanding the factors that predict or perpetuate
      poor sleep in children and adolescents diagnosed with JIA.

PMID- 24940170
TI  - Highly efficient blue organic light-emitting diodes using quantum well-like
      multiple emissive layer structure.
AB  - In this study, the properties of blue organic light-emitting diodes (OLEDs),
      employing quantum well-like structure (QWS) that includes four different blue
      emissive materials of 4,4'-bis(2,2'-diphenylyinyl)-1,1'-biphenyl (DPVBi), 9,10
      di(naphth-2-yl)anthracene (ADN), 2-(N,N-diphenyl-amino)-6-[4-(N,N-diphenyl
      amine)styryl]naphthalene (DPASN), and bis(2-methyl-8-quinolinolate)-4-(phenyl
      phenolato) aluminum (BAlq), were investigated. Conventional QWS blue OLEDs
      composed of multiple emissive layers and charge blocking layer with lower highest
      occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO)
      energy level, and devices with triple emissive layers for more significant hole
      electron recombination and a wider region for exciton generation were designed.
      The properties of triple emissive layered blue OLEDs with the structure of indium
      tin oxide (ITO) /N,N'-diphenyl-N,N'-bis(1-naphthyl-phenyl)-(1,1'-biphenyl)-4,4'
      diamine (NPB) (700 A)/X (100 A)/BAlq (100 A)/X (100 A)/4,7-diphenyl-1,10
      phenanthroline (Bphen) (300 A)/lithium quinolate (Liq) (20 A)/aluminum (Al)
      (1,200 A) (X = DPVBi, ADN, DPASN) were examined. HOMO-LUMO energy levels of
      DPVBi, ADN, DPASN, and BAlq are 2.8 to 5.9, 2.6 to 5.6, 2.3 to 5.2, and 2.9 to
      5.9 eV, respectively. The OLEDs with DPASN/BAlq/DPASN QWS with maximum luminous
      efficiency of 5.32 cd/A was achieved at 3.5 V. 

PMID- 24940169
TI  - The role of sleep in Juvenile idiopathic arthritis patients and their caregivers.
AB  - Juvenile idiopathic arthritis is a chronic disease that may lead to various
      consequences for patients and caregivers, especially in relation to sleep
      quality. Sleep is an essential process for homeostasis of the organism. In
      general, caregivers of children with JIA are more susceptible to these sleep
      disorders and a lower quality of life. This impairment in sleep can potentially
      affect the health of caregiver. For this reason, it is very important to continue
      to evaluate the quality of sleep in caregivers and how to support these JIA
      children's caregivers more effectively. 

PMID- 24940171
TI  - Fabrication of nanochannels with ladder nanostructure at the bottom using AFM
      nanoscratching method.
AB  - This letter presents a novel atomic force microscopy (AFM)-based
      nanomanufacturing method combining the tip scanning with the high-precision stage
      movement to fabricate nanochannels with ladder nanostructure at the bottom by
      continuous scanning with a fixed scan size. Different structures can be obtained
      according to the matching relation of the tip feeding velocity and the precision
      stage moving velocity. This relationship was first studied in detail to achieve
      nanochannels with different ladder nanostructures at the bottom. Machining
      experiments were then performed to fabricate nanochannels on an aluminum alloy
      surface to demonstrate the capability of this AFM-based fabrication method
      presented in this study. Results show that the feed value and the tip orientation
      in the removing action play important roles in this method which has a
      significant effect on the machined surfaces. Finally, the capacity of this method
      to fabricate a large-scale nanochannel was also demonstrated. This method has the
      potential to advance the existing AFM tip-based nanomanufacturing technique of
      the formation these complex structures by increasing the removal speed,
      simplifying the processing procedure and achieving the large-scale
      nanofabrication. 

PMID- 24940172
TI  - Hydrothermal phase transformation of hematite to magnetite.
AB  - Different phases of iron oxide were obtained by hydrothermal treatment of ferric
      solution at 200 degrees C with the addition of either KOH, ethylenediamine (EDA),
      or KOH and EDA into the reaction system. As usually observed, the alpha-Fe2O3
      hexagonal plates and hexagonal bipyramids were obtained for reaction with KOH and
      EDA, respectively. When both KOH and EDA were added into the reaction system, we
      observed an interesting phase transformation from alpha-Fe2O3 to Fe3O4 at low
      temperature hydrothermal conditions. The phase transformation involves the
      formation of alpha-Fe2O3 hexagonal plates, the dissolution of the alpha-Fe2O3
      hexagonal plates, the reduction of Fe(3+) to Fe(2+), and the nucleation and
      growth of new Fe3O4 polyhedral particles. 

PMID- 24940173
TI  - Reduced erbium-doped ceria nanoparticles: one nano-host applicable for
      simultaneous optical down- and up-conversions.
AB  - This paper introduces a new synthesis procedure to form erbium-doped ceria
      nanoparticles (EDC NPs) that can act as an optical medium for both up-conversion
      and down-conversion in the same time. This synthesis process results
      qualitatively in a high concentration of Ce(3+) ions required to obtain high
      fluorescence efficiency in the down-conversion process. Simultaneously, the
      synthesized nanoparticles contain the molecular energy levels of erbium that are
      required for up-conversion. Therefore, the synthesized EDC NPs can emit visible
      light when excited with either UV or IR photons. This opens new opportunities for
      applications where emission of light via both up- and down-conversions from a
      single nanomaterial is desired such as solar cells and bio-imaging. 

PMID- 24940174
TI  - Nanofabrication on monocrystalline silicon through friction-induced selective
      etching of Si3N4 mask.
AB  - A new fabrication method is proposed to produce nanostructures on monocrystalline
      silicon based on the friction-induced selective etching of its Si3N4 mask. With
      low-pressure chemical vapor deposition (LPCVD) Si3N4 film as etching mask on
      Si(100) surface, the fabrication can be realized by nanoscratching on the Si3N4
      mask and post-etching in hydrofluoric acid (HF) and potassium hydroxide (KOH)
      solution in sequence. Scanning Auger nanoprobe analysis indicated that the HF
      solution could selectively etch the scratched Si3N4 mask and then provide the gap
      for post-etching of silicon substrate in KOH solution. Experimental results
      suggested that the fabrication depth increased with the increase of the
      scratching load or KOH etching period. Because of the excellent masking ability
      of the Si3N4 film, the maximum fabrication depth of nanostructure on silicon can
      reach several microns. Compared to the traditional friction-induced selective
      etching technique, the present method can fabricate structures with lesser damage
      and deeper depths. Since the proposed method has been demonstrated to be a less
      destructive and flexible way to fabricate a large-area texture structure, it will
      provide new opportunities for Si-based nanofabrication. 

PMID- 24940175
TI  - BRCAA1 antibody- and Her2 antibody-conjugated amphiphilic polymer engineered
      CdSe/ZnS quantum dots for targeted imaging of gastric cancer.
AB  - Successful development of safe and highly effective nanoprobes for targeted
      imaging of in vivo early gastric cancer is a great challenge. Herein, we choose
      the CdSe/ZnS (core-shell) quantum dots (QDs) as prototypical materials,
      synthesized one kind of a new amphiphilic polymer including dentate-like alkyl
      chains and multiple carboxyl groups, and then used the prepared amphiphilic
      polymer to modify QDs. The resultant amphiphilic polymer engineered QDs (PQDs)
      were conjugated with BRCAA1 and Her2 monoclonal antibody, and prepared BRCAA1
      antibody- and Her2 antibody-conjugated QDs were used for in vitro MGC803 cell
      labeling and in vivo targeted imaging of gastric cancer cells. Results showed
      that the PQDs exhibited good water solubility, strong photoluminescence (PL)
      intensity, and good biocompatibility. BRCAA1 antibody- and Her2 antibody
      conjugated QD nanoprobes successfully realized targeted imaging of in vivo
      gastric cancer MGC803 cells. In conclusion, BRCAA1 antibody- and Her2 antibody
      conjugated PQDs have great potential in applications such as single cell labeling
      and in vivo tracking, and targeted imaging and therapeutic effects' evaluation of
      in vivo early gastric cancer cells in the near future. 

PMID- 24940176
TI  - Photogenerated charges and surface potential variations investigated on single Si
      nanorods by electrostatic force microscopy combined with laser irradiation.
AB  - Photogenerated charging properties of single Si nanorods (Si NRs) are
      investigated by electrostatic force microscopy (EFM) combined with laser
      irradiation. Under laser irradiation, Si NRs are positively charged. The amount
      of the charges trapped in single NRs as well as the contact potential difference
      between the tip and NRs' surface is achieved from an analytical fitting of the
      phase shift - voltage curve. Both of them significantly vary with the laser
      intensity and the NR's size and construction. The photogenerated charging and
      decharging rates are obtained at a timescale of seconds or slower, indicating
      that the Si NRs are promising candidates in photovoltaic applications. 

PMID- 24940177
TI  - A green chemistry approach for synthesizing biocompatible gold nanoparticles.
AB  - Gold nanoparticles (AuNPs) are a fascinating class of nanomaterial that can be
      used for a wide range of biomedical applications, including bio-imaging, lateral
      flow assays, environmental detection and purification, data storage, drug
      delivery, biomarkers, catalysis, chemical sensors, and DNA detection. Biological
      synthesis of nanoparticles appears to be simple, cost-effective, non-toxic, and
      easy to use for controlling size, shape, and stability, which is unlike the
      chemically synthesized nanoparticles. The aim of this study was to synthesize
      homogeneous AuNPs using pharmaceutically important Ganoderma spp. We developed a
      simple, non-toxic, and green method for water-soluble AuNP synthesis by treating
      gold (III) chloride trihydrate (HAuCl4) with a hot aqueous extract of the
      Ganoderma spp. mycelia. The formation of biologically synthesized AuNPs (bio
      AuNPs) was characterized by ultraviolet (UV)-visible absorption spectroscopy, X
      ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy
      dispersive X-ray (EDX), dynamic light scattering (DLS), and transmission electron
      microscopy (TEM). Furthermore, the biocompatibility of as-prepared AuNPs was
      evaluated using a series of assays, such as cell viability, lactate dehydrogenase
      leakage, and reactive oxygen species generation (ROS) in human breast cancer
      cells (MDA-MB-231). The color change of the solution from yellow to reddish pink
      and strong surface plasmon resonance were observed at 520 nm using UV-visible
      spectroscopy, and that indicated the formation of AuNPs. DLS analysis revealed
      the size distribution of AuNPs in liquid solution, and the average size of AuNPs
      was 20 nm. The size and morphology of AuNPs were investigated using TEM. The
      biocompatibility effect of as-prepared AuNPs was investigated in MDA-MB-231
      breast cancer cells by using various concentrations of AuNPs (10 to 100 MUM) for
      24 h. Our findings suggest that AuNPs are non-cytotoxic and biocompatible. To the
      best of our knowledge, this is the first report to describe the synthesis of
      monodispersed, biocompatible, and soluble AuNPs with an average size of 20 nm
      using Ganoderma spp. This study opens up new possibilities of using an
      inexpensive and non-toxic mushroom extract as a reducing and stabilizing agent
      for the synthesis of size-controlled, large-scale, biocompatible, and
      monodispersed AuNPs, which may have future diagnostic and therapeutic
      applications. 

PMID- 24940178
TI  - CeO2-based catalysts with engineered morphologies for soot oxidation to enhance
      soot-catalyst contact.
AB  - AS MORPHOLOGY PLAYS A RELEVANT ROLE IN SOLID/SOLID CATALYSIS, WHERE THE NUMBER OF
      CONTACT POINTS IS A CRITICAL FEATURE IN THIS KIND OF REACTION, THREE DIFFERENT
      CERIA MORPHOLOGIES HAVE BEEN INVESTIGATED IN THIS WORK AS SOOT OXIDATION
      CATALYSTS: ceria nanofibers, which can become organized as a catalytic network
      inside diesel particulate filter channels and thus trap soot particles at several
      contact points but have a very low specific surface area (4 m(2)/g); solution
      combustion synthesis ceria, which has an uncontrolled morphology but a specific
      surface area of 31 m(2)/g; and three-dimensional self-assembled (SA) ceria stars,
      which have both high specific surface area (105 m(2)/g) and a high availability
      of contact points. A high microporous volume of 0.03 cm(3)/g and a finer
      crystallite size compared to the other morphologies suggested that self-assembled
      stars could improve their redox cycling capability and their soot oxidation
      properties. In this comparison, self-assembled stars have shown the best tendency
      towards soot oxidation, and the temperature of non-catalytic soot oxidation has
      dropped from 614 degrees C to 403 degrees C in tight and to 552 degrees C in
      loose contact conditions, respectively. As far as the loose contact results are
      concerned, this condition being the most realistic and hence the most
      significant, self-assembled stars have exhibited the lowest T 10% onset
      temperature of this trio (even after ageing), thus proving their higher intrinsic
      activity. Furthermore, the three-dimensional shape of self-assembled stars may
      involve more of the soot cake layer than the solution combustion synthesis or
      nanofibers of ceria and thus enhance the total number of contact points. The
      results obtained through this work have encouraged our efforts to understand soot
      oxidation and to transpose these results to real diesel particulate filters. 

PMID- 24940179
TI  - Gold-silicon nanofiber synthesized by femtosecond laser radiation for enhanced
      light absorptance.
AB  - In this study, we devised a new concept for the precise nanofabrication of Au-Si
      fibrous nanostructures using megahertz femtosecond laser irradiation in air and
      atmospheric pressure conditions. The weblike fibrous nanostructures of Au thin
      layer on silicon substrate, which are proposed for the application of solar
      cells, exhibit a specific improvement of the optical properties in visible
      wavelength. Varying numbers of laser interaction pulses were used to control the
      synthesis of the nanofibrous structures. Electron microscopy analysis revealed
      that the nanostructures are formed due to the aggregation of polycrystalline
      nanoparticles of the respective constituent materials with diameters varying
      between 30 and 90 nm. Measurement of the reflectance through a spectroradiometer
      showed that the coupling of incident electromagnetic irradiation was greatly
      improved over the broadband wavelength range. Lower reflectance intensity was
      obtained with a higher number of laser pulses due to the bulk of gold
      nanoparticles being agglomerated by the mechanism of fusion. This forms
      interweaving fibrous nanostructures which reveal a certain degree of assembly.
      PACS: 81.05.Zx; 81.07.-b.

PMID- 24940180
TI  - Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a
      modified coaxial electrospinning process.
AB  - This manuscript reports a new type of drug-loaded core-shell nanofibers that
      provide tunable biphasic release of quercetin. The nanofibers were fabricated
      using a modified coaxial electrospinning process, in which a polyvinyl chloride
      (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP)
      and ethyl cellulose (EC) were used as the polymer matrices to form the shell and
      core parts of the nanofibers, respectively. Scanning and transmission electron
      microscopy demonstrated that the nanofibers had linear morphologies and core
      shell structures. The quercetin was found to be present in the nanofibers in the
      amorphous physical status, on the basis of X-ray diffraction results. In vitro
      release profiles showed that the PVP shell very rapidly freed its drug cargo into
      the solution, while the EC core provided the succedent sustained release.
      Variation of the drug loading permitted the release profiles to be tuned. 

PMID- 24940181
TI  - Abnormal coexistence of unipolar, bipolar, and threshold resistive switching in
      an Al/NiO/ITO structure.
AB  - This paper reports an abnormal coexistence of different resistive switching
      behaviors including unipolar (URS), bipolar (BRS), and threshold switching (TRS)
      in an Al/NiO/indium tin oxide (ITO) structure fabricated by chemical solution
      deposition. The switching behaviors have been strongly dependent on compliance
      current (CC) and switching processes. It shows reproducible URS and BRS after
      electroforming with low and high CC of 1 and 3 mA, respectively, which is
      contrary to previous reports. Furthermore, in the case of high-forming CC, TRS is
      observed after several switching cycles with a low-switching CC. Analysis of
      current-voltage relationship demonstrates that Poole-Frenkel conduction
      controlled by localized traps should be responsible for the resistance switching.
      The unique behaviors can be dominated by Joule heating filament mechanism in the
      dual-oxygen reservoir structure composed of Al/NiO interfacial layer and ITO. The
      tunable switching properties can render it flexible for device applications. 

PMID- 24940183
TI  - alpha-NH4Fe(HAsO4)2.
AB  - The title compound alpha-ammonium iron(III) bis-[hydro-gen arsenate(V)], alpha
      NH4Fe(HAsO4)2 (or poly[ammonium bis-(MU-hydro-gen arsenato)ferrate(III)],
      {NH4[Fe(HAsO4)2]} n ), syn-the-sized hydro-thermally, is isostructural with
      NH4Fe(HPO4)2. Condensation of the hydro-gen arsenate groups with FeO6
      coordination octa-hedra via common corners results in an overall three
      dimensional framework containing inter-connected channels parallel to the a-, b-
      and c-axis directions. The NH4 (+) cations are located in three inter-secting
      tunnels, which is promising as an ion exchange. Hydrogen bonding of the types O
      H?O and N-H?O consolidates the packing of the structure. The distortion of the
      coordination polyhedra is analyzed by means of the effective coordination number
      and distortion indices. Structural relationships with other compounds of general
      formula M (I) M (III)[HXO4)]2 (X = P, As) are discussed. 

PMID- 24940182
TI  - Nanotechnologies in glycoproteomics.
AB  - Protein glycosylation, as an important post-translational modification, is
      implicated in a number of ailments. Applying proteomic approaches, including mass
      spectrometry (MS) analyses that have played a significant role in biomarker
      detection and early diagnosis of diseases, to the study of glycoproteins or
      glycopeptides will facilitate a deeper understanding of many physiological
      functions and biological pathways involved in cancer, inflammatory and
      degenerative diseases. The abundance of glycopeptides and their ionization
      potential are relatively lower compared to those of non-glycopeptides; therefore,
      sample enrichment is necessary for glycopeptides prior to MS analysis. The
      application of nanotechnology in the past decade has been rapidly penetrating
      into many diverse scientific research disciplines. Particularly in what we now
      refer to as the "glycoproteomics area", nanotechnologies have enabled enhanced
      sensitivity and specificity of glycopeptide detection in complex biological
      fluids, which are critical for disease diagnosis and monitoring. In this review,
      we highlight some recent studies that combine the capabilities of specific
      nanotechnologies with the comprehensive features of glycoproteomics. In
      particular, we focus on the ways in which nanotechnology has facilitated the
      detection of glycopeptides in complex biological samples and enhanced their
      characterization by MS, in terms of intensity and resolution. These studies
      reveal an increasingly important role for nanotechnology in helping to overcome
      certain technical challenges in biomarker discovery, in general, and
      glycoproteomics research, in particular. 

PMID- 24940184
TI  - La3Si6N11.
AB  - Colorless transparent single crystals of trilanthanum hexa-silicon undeca-nitro
      gen, La3Si6N11, were prepared at 0.85 MPa of N2 and 2273 K. The title compound is
      isotypic with Sm3Si6N11. Silicon-centered nitro-gen tetra-hedra form a three
      dimensional network structure by sharing their corners. Layers of one type of
      SiN4 tetra-hedra and slabs composed of the two different La(3+) cations and the
      other type of SiN4 tetra-hedra are alternately stacked along the c axis of the
      tetra-gonal unit cell. The site symmetries of the two La(3+) cations are are ..m
      and 4.., respectively. 

PMID- 24940185
TI  - Cs3ScCl6.
AB  - Crystals of tricaesium scandium(III) hexa-chloride were obtained as a side
      product from the reaction of U, SnCl2, Sc, and S in a CsCl flux at 1073 K.
      Cs3ScCl6 crystallizes in the Rb3YCl6 structure type. The asymmetric unit
      comprises three Cs sites, two Sc sites, and six Cl sites, all of which have site
      symmetry 1, except for the two Sc sites that have site symmetries of 2 and -1,
      respectively. The structure is composed of isolated [ScCl6](3-) octa-hedra that
      are surrounded by Cs(+) cations. Two Cs(+) cations have inter-actions with eight
      Cl(-) anions, while the third has inter-actions with ten Cl(-) anions. 

PMID- 24940186
TI  - Nickel hexa-yttrium deca-iodide, [NiY6]I10.
AB  - Comproportionation reactions of yttrium triiodide, yttrium and nickel led to the
      formation of the compound [NiY6]I10, which is isostructural with the prototypical
      [RuY6]I10. In particular, [NiY6]I10 is composed of isolated nickel centered
      yttrium octa-hedra (site symmetry -1) that are further surrounded by iodide
      ligands to construct a three-dimensional cluster complex framework. Although this
      compound has been previously detected by powder X-ray diffraction techniques
      [Payne & Corbett (1990 ?). Inorg. Chem. 29, 2246-2251], details of the crystal
      structure for triclinic [NiY6]I10 were not provided. 

PMID- 24940187
TI  - Redetermination of [EuCl2(H2O)6]Cl.
AB  - The crystal structure of the title compound, hexa-aqua-dichlorido-europium(III)
      chloride, was redetermined with modern crystallographic methods. In comparison
      with the previous study [Lepert et al. (1983 ?). Aust. J. Chem. 36, 477-482], it
      could be shown that the atomic coordinates of some O atoms had been confused and
      now were corrected. Moreover, it was possible to freely refine the positions of
      the H atoms and thus to improve the accurracy of the crystal structure.
      [EuCl2(H2O)6]Cl crystallizes with the GdCl3.6H2O structure-type, exhibiting
      discrete [EuCl2(H2O)6](+) cations as the main building blocks. The main blocks
      are linked with isolated chloride anions via O-H?Cl hydrogen bonds into a three
      dimensional framework. The Eu(3+) cation is located on a twofold rotation axis
      and is coordinated in the form of a Cl2O6 square anti-prism. One chloride anion
      coordinates directly to Eu(3+), whereas the other chloride anion, situated on a
      twofold rotation axis, is hydrogen bonded to six octa-hedrally arranged water mol
      ecules. 

PMID- 24940188
TI  - Ba4GaN3O.
AB  - Red transparant platelet-shaped single crystals of tetra-barium gallium
      trinitride oxide, Ba4GaN3O, were synthesized by the Na flux method. The crystal
      structure is isotypic with Sr4GaN3O, containing isolated triangular [GaN3](6-)
      anionic groups. O(2-) atoms are inserted between the slabs of [Ba4GaN3](2+), in
      which the [GaN3](6-) groups are surrounded by Ba(2+) atoms. 

PMID- 24940189
TI  - Cs5Sn9(OH).4NH3.
AB  - The title compound, penta-caesium nona-stannide hydroxide tetra-ammonia,
      crystallized from a solution of CsSnBi in liquid ammonia. The Sn9 (4-) unit forms
      a monocapped quadratic anti-prism. The hydroxide ion is surrounded by five
      caesium cations, which form a distorted quadratic pyramidal polyhedron. A three
      dimensional network is formed by Cs-Sn [3.8881 (7) A to 4.5284 (7) A] and Cs-NH3
      [3.276 (7)-3.636 (7) A] contacts. 

PMID- 24940190
TI  - Na4.25Mo15S19: a novel ternary reduced molybdenum sulfide containing Mo6 and Mo9
      clusters.
AB  - The structure of tetra-sodium penta-deca-molybdenum nona-deca-sulfide,
      Na4.25Mo15S19, is isotypic with Na3.9Mo15Se19 [Salloum et al. (2013 ?). Acta
      Cryst. E69, i67-i68]. It is characterized by Mo6S (i) 8S (a) 6 and Mo9S (i) 11S
      (a) 6 (where i represents inner and a apical atoms) cluster units that are
      present in a 1:1 ratio. The cluster units are centered at Wyckoff positions 2b
      and 2c, and have point-group symmetry -3 and -6, respectively. The clusters are
      inter-connected through additional Mo-S bonds. The Na(+) cations occupy inter
      unit voids formed by six or seven S atoms. One Mo, one S and one Na site
      [occupancy 0.751 (12)] are situated on mirror planes, and two other S atoms and
      one Na site (full occupancy) are situated on threefold rotation axes. 

PMID- 24940191
TI  - catena-Poly[[bis-(pyridine-kappaN)nickel(II)]-di-MU-thio-cyanato-kappa(2)
      N:S;kappa(2) S:N].
AB  - In the title compound, [Ni(NCS)2(C5H5N)2] n , the Ni(2+) cation is coordinated by
      four thio-cyanate anions (MU-1,3) and two pyridine ligands within a slightly
      distorted octa-hedral configuration. The Ni-N bond lengths to the pyridine rings
      are 2.1189 (17) and 2.1241 (17) A, whereas those to the thiocyanate anions are
      2.0299 (18) and 2.0359 A. The Ni-S bond lengths are 2.5357 (6) and 2.5568 (6) A.
      The Ni(2+) cations are linked by N:S-bridging thio-cyanate ligands into chains
      extending along [010]. The Ni?Ni distance within the chains is 5.5820 (5) A. The
      asymmetric unit contains two Ni(2+) cations of which one is located on a centre
      of inversion, whereas the second is located on a general position. 

PMID- 24940192
TI  - Di-chlorido-(N,N-diethyl-4-{[(quinolin-2-yl)methyl-idene]amino-kappa(2)
      N,N'}aniline)mercury(II).
AB  - In the mononuclear title complex, [HgCl2(C20H21N3)], synthesized from the
      quinoline-derived Schiff base N (1),N (1)-diethyl-N (4)-(quinolin-2-yl-methyl
      idene)benzene-1,4-di-amine (QMBD), the coordination geometry around the Hg(2+)
      atom is distorted tetra-hedral, comprising two Cl atoms [Hg-Cl = 2.3654 (19) and
      2.4394 (18) A] and two N-atom donors from the QMBD ligand, viz. one imine and
      quinoline [Hg-N = 2.334 (5) and 2.340 (5) A, respectively]. In the crystal, weak
      C-H?Cl hydrogen bonds and weak pi-pi aromatic ring stacking inter-actions
      [minimum ring-centroid separation = 3.680 (4) A] give an overall three
      dimensional network. 

PMID- 24940193
TI  - Poly[[di-aqua-[MU-1,4-bis(pyridin-4-ylmeth-yl)piperazine-kappa(2) N:N']{MU-2,2'
      [(1,4-phenyl-ene)bis(-oxy)]di-acetato-kappa(2) O:O'}cobalt(II)] penta-hydrate].
AB  - In the title compound, {[Co(C10H8O6)(C16H20N4)(H2O)2].5H2O} n , octa-hedrally
      coordinated Co(II) ions on crystallographic inversion centres are bound by trans
      O atoms belonging to two hydro-quinone-O,O'-di-acetate (hqda) anions {systematic
      name: 2,2'-[(1,4-phenyl-ene)bis-(-oxy)]di-acetate}, two trans-pyridine N-donor
      atoms from two bis-(pyridin-4-ylmeth-yl)piperazine (4-bpmp) ligands, and two
      trans aqua ligands. The exobidentate hqda and 4-bpmp ligands form [Co(hqda)(4
      bpmp)(H2O)2] n coordination polymer layers parallel to (110) that are anchored
      into the full crystal structure by O-H?O hydrogen bonding between aqua ligands
      and ligated hqda O atoms. Disordered water mol-ecules of crystallization occupy
      incipient channels along [100]. However, these could not modeled reliably and so
      they were treated with SQUEEZE in PLATON [Spek (2009 ?). Acta Cryst. D65, 148
      155]; the crystal data take the presence of these mol-ecules into account. The
      crystal under investigation was twinned by non-merohedry, the twin fraction of
      the components being 53.3% and 46.7%. Only data from the major twin component
      were used in the refinement. 

PMID- 24940194
TI  - Di-chlorido-(4,4'-di-tert-butyl-2,2'-bi-pyridine-kappa(2) N,N')palladium(II)
      dimethyl sulfoxide monosolvate monohydrate.
AB  - The title compound, [PdCl2(C18H24N2)].(CH3)2SO.H2O, the Pd(II) ion is in a
      distorted square-planar geometry. The Pd-N bond distances are 2.022 (2) and 2.027
      (2) A, the Pd-Cl bond distances are 2.2880 (7) and 2.2833 (7) A, and the ligand
      bite angle is 80.07 (9) degrees . The dimethyl sulfoxide and water mol-ecules
      form linear chains along [100] by O-H?O and O-H?S hydrogen bonds, generating
      eight- and 12-membered rings. C-H?Cl inter-actions link the chains, forming a
      three-dimensional arrangement. In addition, the 4,4-di-tert-butyl-2,2'-bi
      pyridine ligand exhibits pi-pi stacking inter-actions [centroid-centroid
      distances = 3.8741 (15) and 3.8353 (15) A]. The DMSO solvent is disordered and
      was refined with an occupancy ratio of 0.866 (3):0.134 (3). 

PMID- 24940195
TI  - Bis(1-methyl-piperazine-1,4-diium) di-MU-bromido-bis-[tetra-bromido
      bismuthate(III)] dihydrate.
AB  - In the title hydrated salt, (C5H14N2)2[Bi2Br10].2H2O, the com-plete [Bi2Br10](4-)
      biocta-hedron is generated by crystallographic inversion symmetry. The
      diprotonated piperazine ring adopts a chair conformation, with the methyl group
      occupying an equatorial position. In the crystal, the tetra-anions and water mol
      ecules are linked by O-H?Br and O-H?(Br,Br) hydrogen bonds to generate [100]
      chains. The chains are crosslinked by N-H?Br, N-H?O and C-H?Br hydrogen bonds
      originating from the piperazinediium dications, thereby forming a three
      dimensional network. 

PMID- 24940196
TI  - [MU-Butane-1,4-diylbis(di-phenyl-phos-phane)-kappa(2) P:P']bis-{[butane-1,4
      diylbis(di-phenyl-phosphane)-kappa(2) P,P']copper(I)} bis-(hexa-fluorido
      phosphate) diethyl ether disolvate.
AB  - In the centrosymmetric dinuclear copper(I) complex cation of the title compound,
      [Cu2(C28H28P2)3](PF6)2.2C4H10O, the Cu(I) atom is bonded to three P atoms of two
      butane-1,4-diylbis(di-phenyl-phosphane) (dppb) ligands with a triangular
      coordination geometry. One of these P atoms belongs to a bridging dppb ligand [Cu
      P = 2.2381 (5) A] and two belong to a chelating dppb ligand [Cu-P = 2.2450 (6)
      and 2.2628 (5) A]. The bridging dppb ligand lies on an inversion centre. In the
      crystal, the cation and the PF6 (-) anion are linked by C-H?F inter-actions,
      forming a tape along [110]. The cation and the diethyl ether solvent mol-ecule
      are also linked by a C-H?O inter-action. 

PMID- 24940197
TI  - [Bis(quinolin-2-ylcarbon-yl)amido-kappa(3) N,N',N'']bromido-(N,N-di-methyl
      formamide-kappaO)copper(II).
AB  - In the mononuclear title complex, [CuBr(C20H12N3O2)(C3H7NO)], synthesized from
      the quinoline-derived reduced Schiff base 4-(quinolin-2-ylmeth-yl)amino-phenol,
      the coordination geometry around Cu(2+) is distorted square-pyramidal, comprising
      a bromide anion at the apex [Cu-Br = 2.4671 (5) A]. The base of the pyramid is
      built up from one di-methyl-formamide O-atom donor [Cu-O = 2.078 (2) A] and three
      N-atom donors from the monoanionic, tridentate bis-(quinolin-2-ylcarbon-yl)di
      imide ligand [Cu-Ndi-imide = 1.941 (3) A, and Cu-Nquinol-yl = 2.060 (3) and 2.049
      (3) A]. An intra-molecular C-H?O occurs. In the crystal, weak methyl and aromatic
      C-H?Br and formyl C-H?Ocarbon-yl hydrogen-bonding inter-actions generate an
      overall layered structure lying parallel to (001). 

PMID- 24940198
TI  - catena-Poly[[di-chlorido-mercury(II)]-MU-1,4-bis-[2-(pyridin-4-yl)ethyn
      yl]benzene-kappa(2) N:N'].
AB  - In the polymeric title compound, [HgCl2(C20H12N2)] n , the Hg(II) atom is located
      on a twofold rotation axis and the benzene ring of the bidentate bridging 1,4-bis
      [2-(pyridin-4-yl)ethyn-yl]benzene (L) ligand is located about a twofold rotation
      axis. The Hg(II) atom is coordinated by two N atoms of two different L ligands
      and by two chloride ions in a distorted tetra-hedral geometry. The dihedral angle
      between the coordinating pyridine and the benzene ring is 12.8 (2) degrees . The
      result of the bridging is the formation of a zigzag chain running parallel to
      [102]. The chains pack with no specific inter-molecular inter-actions between
      them. 

PMID- 24940199
TI  - {Dimeth-yl [(phenyl-sulfon-yl)amido-]phosphato-kappa(2) O,O'}bis-(tri
      phenylphosphane-kappaP)copper(I).
AB  - In the title complex, [Cu(C8H11NO5PS)(C18H15P)2], the Cu(I) ion is coordinated by
      two tri-phenyl-phosphane mol-ecules and two O atoms of the chelating dimeth
      yl(phenyl-sulfon-yl)amido-phosphate anion, generating a squashed CuO2P2
      tetrahedron. In the six-membered chelate ring, the Cu, P and O atoms are almost
      coplanar (r.m.s. deviation = 0.024 A), with the N and S atoms displaced in the
      same direction, by 0.708 (5) and 0.429 (2) A, respectively. 

PMID- 24940200
TI  - Bis{MU-N-[(E)-4-benz-yloxy-2-oxidobenzyl-idene]-4-nitro-benzene-carbo
      hydrazidato}bis-[di-aqua-nickel(II)] di-methyl-formamide tetra-solvate.
AB  - The molecule of the title complex, [Ni2(C21H15N3O5)2(H2O)4].4C3H7NO, is located
      on an inversion centre. This results in a dimeric Ni(II) complex, with the two
      Ni(II) atoms bridged by phenolate O atoms. The tridentate ligand is chelated to
      each Ni(II) atom via one N and two O atoms of the imino-late form of the
      hydrazide moiety, which has the same conformation as the free ligand. The
      coordination geometry around each Ni(II) ion is slightly distorted octa-hedral. A
      supra-molecular three-dimensional architecture is created by dominant inter
      molecular O-H?N, O-H?O and C-H?O hydrogen-bonding inter-actions. These are
      augmented by two C-H?pi inter-actions and a pi-pi inter-action with a centroid
      centroid distance of 3.681 (2) A. 

PMID- 24940201
TI  - Di-MU-chlorido-bis-(chlorido-{N'-[phen-yl(pyridin-2-yl-kappaN)methyl
      idene]pyridine-2-carbohydrazide-kappa(2) N',O}cadmium).
AB  - The title compound, [Cd2Cl4(C18H14N4O)2], was obtained from the reaction of
      Cd(NO3)2.4H2O with 2-phenyl-pyridine-keton picolinoyl hydrazone and sodium
      chloride. Each Cd(2+) cation is coordinated by two N atoms and one O atom of the
      tridentate ligand and three chloride anions, forming a distorted CdNOCl3
      octahedron. Each pair of adjacent metal cations is linked by two bridging
      chloride ligands, resulting in a dinuclear complex unit. The mol-ecular
      conformation is stabilized by intra-molecular N-H?N and C-H?O hydrogen bonds. In
      the crystal, mol-ecules are linked by nonclassical C-H?O and C-H?Cl hydrogen
      bonds into a three-dimensional network. In addition, pi-pi stacking inter-actions
      [centroid-centroid distances = 3.777 (2) and 3.631 (2) A] contribute to the
      stabilization of the crystal packing. 

PMID- 24940202
TI  - Chlorido-{2-[(di-methyl-amino)-meth-yl]benzene-seleno-lato-kappa(2) N,Se}(tri
      phenyl-phosphane-kappaP)palladium(II).
AB  - The asymmetric unit of the title compound, [PdCl(C9H12NSe)(C18H15P)], contains
      two independent mol-ecules. In both cases, the Pd(2+) cations are coordinated by
      the Se and N atoms of the chelating bidentate 2-[(di-methyl-amino)-meth
      yl]benzene-seleno-late ligand. The chloride ligand lies trans to selenium and the
      tri-phenyl-phosphane ligand is trans to nitro-gen. The Pd-Se bond lengths in the
      two independent coordination environments of Pd are 2.3801 (4) and 2.3852 (4) A,
      the Pd-P bond lengths are 2.2562 (8) and 2.2471 (8) A, the Pd-N bond lengths are
      2.172 (2) and 2.158 (2) A, and the Pd-Cl bond lengths are 2.3816 (8) and 2.3801
      (8) A. The square-planar coordination around one Pd(2+) cation is less distorted
      than that around the other. 

PMID- 24940203
TI  - (N,N'-Di-ethyl-thio-urea-kappaS)tris-(triphenylphosphane-kappaP)silver(I) acetate
      methanol monosolvate.
AB  - In the mononuclear title complex, [Ag(C5H12N2S)(C18H15P)3](CH3COO).CH3OH, the
      Ag(I) ion is in a distorted tetra-hedral coordination geometry formed by three P
      atoms from three tri-phenyl-phosphane ligands and one S atom from an N,N'-di
      ethyl-thio-urea ligand. In the crystal, the acetate anion is connected to the
      complex mol-ecule via a pair of N-H?O hydrogen bonds [graph-set motif R (2) 2(8)]
      and the solvent methanol mol-ecule is connected to the anion via an O-H?O
      hydrogen bond. This aggregate is further connected through a weak C-H?O hydrogen
      bond, forming a chain along [100]. In addition, sixfold phenyl embraces with
      inter-molecular distances of 6.6463 (13)-6.667 (2) A are arranged in a chain
      along [001]. The combination of hydrogen bonding and phen-yl?phenyl inter-actions
      leads to the formation of a two-dimensional network parallel to (010). 

PMID- 24940205
TI  - (Aceto-nitrile-kappaN)iodidobis(tri-phenylphosphane-kappaP)copper(I).
AB  - In the mononuclear title complex, [CuI(CH3CN)(C18H15P)2], the Cu(I) ion is in a
      distorted tetra-hedral geometry, coordinated by two P atoms of two tri-phenyl
      phosphane ligands, one N atom of an aceto-nitrile ligand and one iodide anion.
      The aceto-nitrile ligand is disordered over two sets of sites in a 0.629 (15):
      0.371 (15) ratio. In the crystal, weak C-H?I hydrogen bonds link the mol-ecules,
      forming a chain along [100]. 

PMID- 24940204
TI  - (2,2'-Bi-pyridine-kappa(2) N,N')di-chloridopalladium(II) 1,4-dioxane hemisolvate.
AB  - The asymmetric unit of the title compound, [PdCl2(C10H8N2)].0.5C4H8O2, consists
      of one Pd(II) complex mol-ecule and a half-mol-ecule of 1,4-dioxane, the complete
      mol-ecule being generated by inversion symmetry. The Pd(II) atom has an almost
      square-planar coordination formed by the 2,2'-bi-pyridine ligand and two chloride
      ligands. Two intra-molecular C-H?Cl hydrogen bonds occur. In the crystal, the
      Pd(II) complex and 1,4-dioxane mol-ecules are connected by C-H?O hydrogen bonds,
      forming a layer parallel to (10-1). Within the layer, weak pi-pi inter-actions
      [centroid-centroid distance = 3.817 (4) A] are observed between the pyridine
      rings. 

PMID- 24940206
TI  - Bis(cyclo-hexyl-ammonium) tetra-chlorido-diphenyl-stannate(IV).
AB  - The title compound, (C6H14N)2[Sn(C6H5)2Cl4], contains cyclo-hexyl-ammonium
      cations in general positions and a stannate(IV) anion that is located on a
      twofold rotation axis. The Sn(IV) atom in the complex anion is surrounded by four
      Cl(-) ligands and two trans-phenyl groups in a distorted octa-hedral
      configuration. The anions are connected with the cations through N-H?Cl hydrogen
      bonds. Every cation is involved in three N-H?Cl bonds to the chloride ligands of
      three different anions, and each chloride ligand is linked to two cations. This
      arrangement leads to a layered structure parallel to (010). 

PMID- 24940207
TI  - Di-aqua-bis-(ethyl-enedi-amine-kappa(2) N,N')copper(II) bis-(sulfamerazinate).
AB  - The asymmetric unit of the title compound, [Cu(C2H8N2)2(H2O)2](C11H11N4O2S)2,
      contains one sulfamerazinate anion in a general position and one half-cation that
      is located on a center of inversion. The Cu(II) cation shows a strong Jahn-Teller
      distortion. It is coordinated by four N atoms of two ethyl-enedi-amine ligands in
      the basal plane and two O atoms at much longer distances in the axial positions
      in a bipyramidal coordination. In the crystal, the building blocks are connected
      by N-H?N, O-H?N, N-H?O and O-H?O hydrogen bonding into a two-dimensional network
      parallel to (001). 

PMID- 24940208
TI  - Bis(MU2-di-phenyl-phosphinamide-kappa(2) O:O)bis-[bis(di-phenyl-phosphinamide
      kappaO)lithium] dichloride aceto-nitrile disolvate.
AB  - The asymmetric unit of the title compound, [Li2(C12H12NOP)6]Cl2.2CH3CN, contains
      one-half of the centrosymmetric dication, one chloride anion and one aceto
      nitrile solvent mol-ecule. Each Li atom is coordinated by four O atoms [Li-O
      1.891 (3) and 2.025 (3) A] from the four di-phenyl-phosphinamide ligands in a
      distorted tetra-hedral geometry. In the crystal, weak N-H?Cl hydrogen bonds link
      the anions and dications into columns extending along [100]. 

PMID- 24940209
TI  - Tetrakis(2,6-di-methyl-pyridinium) di-hydrogen deca-vanadate dihydrate.
AB  - The structure of the title compound, (C7H10N)4[H2V10O28].2H2O, was solved from a
      non-merohedrally twinned crystal (ratio of twin components ~0.6:0.4). The
      asymmetric unit consists of one-half deca-vanadate anion (the other half
      completed by inversion symmetry), two 2,6-di-methyl-pyridinium cations and one
      water mol-ecule of crystallization. In the crystal, the components are connected
      by strong N-H?O and O-H?O hydrogen bonds, forming a supra-molecular chain along
      the b-axis direction. There are weak C-H?O inter-actions between the chains. 

PMID- 24940211
TI  - Bis(tetra-phenyl-phospho-nium) tetra-chlorido-cobaltate(II).
AB  - The title compound, (C24H20P)2[CoCl4], was prepared under hydro-thermal
      conditions. In the crystal, the tetra-phenyl-phospho-nium cations are linked by
      pairs of weak C-H?pi inter-actions into supra-molecular dimers; the Co(II)
      cations lie on twofold rotation axes and the tetra-hedral [CoCl4](2-) anions are
      linked with the tetra-phenyl-phospho-nium cations via weak C-H?Cl hydrogen bonds.

PMID- 24940210
TI  - Bis[tris(propane-1,3-diamine-kappa(2) N,N')-nickel(II)] di-aqua-bis(propane-1,3
      di-amine-kappa(2) N,N')nickel(II) hexa-bromide dihydrate.
AB  - In the title compound, [Ni(C3H10N2)3]2[Ni(C3H10N2)2(H2O)2]Br6.2H2O, one Ni(2+)
      cation, located on an inversion centre, is coordinated by four N atoms from two
      ligands and by two water O atoms. The other Ni(2+) cation, located in a general
      position, is coordinated by six N atoms from three ligands. In both cases, the
      Ni(2+) cation has an octa-hedral coordination environment. The overall structural
      cohesion is ensured by three types of hydrogen bonds, N-H?Br, O-H?Br and O-H?O,
      which connect the two types of complex cations, the bromide counter-anions and
      the lattice water molecules into a three-dimensional network. 

PMID- 24940212
TI  - 1,8-Di-aza-bicyclo-[5.4.0]undec-7-en-8-ium bromido-(phthalocyaninato)zincate.
AB  - The title compound, (C9H17N2)[ZnBr(C32H16N8)], contains a bromido
      (phthalocyaninato)zincate anion and a protonated 1,8-di-aza-bicyclo-[5.4.0]undece
      7-ene cation, [DBUH](+). The central Zn(II) atom has a distorted square-pyramidal
      geometry, with four iso-indole N atoms of the macrocycle in equatorial positions
      and a bromide ion in the axial position. The latter has a relatively high
      displacement parameter, but no evidence for disorder was obtained. The central
      Zn(II) atom is displaced by 0.488 (3) A from the mean plane defined by the four
      iso-indole N atoms. The [DBUH](+) cation is involved in an almost linear N-H?Br
      hydrogen bond. In the crystal, pi-pi inter-actions lead to a relatively short
      distance of 3.366 (3) A between the phthalocyaninate rings. 

PMID- 24940213
TI  - catena-Poly[[silver(I)-MU-N-[(pyridin-2-yl)meth-yl]pyridine-3-amine-kappa(2)
      N:N'] hexa-fluorido-phosphate].
AB  - In the title polymeric complex, {[Ag(C11H11N3)]PF6} n , the Ag(I) ion is two
      coordinated in a nearly linear coordination geometry [N-Ag-N = 175.98 (9) degrees
      ] by two pyridine N atoms from two symmetry-related N-[(pyridine-2-yl)meth
      yl]pyridine-3-amine ligands. Each Ag(I) ion is bridged by the ligands, forming a
      helical chain propagating along the b-axis direction. The right- and left-handed
      helical chains are alternately arranged via Ag?Ag [3.2639 (5) A] and pi-pi
      stacking inter-actions [centroid-centroid distance = 3.523 (1) A], resulting in
      the formation of a two-dimensional supra-molecular network extending parallel to
      (101). Weak Ag?F inter-actions [longest Ag?F inter-action = 3.153 (2) A], as well
      as N-H?F and C-H?F hydrogen-bonding inter-actions, occur between the helical
      chains and the anions. 

PMID- 24940214
TI  - catena-Poly[[lithium-MU2-(di-hydrogen pyrazine-2,3,5,6-tetra-carboxyl-ato)
      kappa(6) O (2),N (1),O (6);O (3),N (4),O (5)-lithium-di-MU-aqua-kappa(4) O:O] 2.5
      hydrate].
AB  - The title coordination polymer, {[Li2(C8H2N2O8)(H2O)2].2.5H2O} n , is built up
      from mol-ecular ribbons propagating in the c-axis direction of the ortho-rhom-bic
      unit cell; the ligand bridges two Li(+) ions using both its N,O,O'-bonding sites
      and adjacent Li(+) ions are bridged by pairs of water mol-ecules. The
      coordination geometry of the metal ion is distorted trigonal bipyramidal, with
      the ligand O atoms in the axial sites. Two of the carboxyl-ate groups of the
      ligand remain protonated and form short symmetric O-H?O hydrogen bonds. In the
      crystal, the ribbons inter-act via a network of O-H?O hydrogen bonds in which
      coordinating water mol-ecules act as donors and carboxyl-ate O atoms within
      adjacent ribbons act as acceptors, giving rise to a three-dimensional framework.
      O-H?N inter-actions are also observed. The asymmetric unit contains quarter of
      the ligand and the complete ligand has 2/m symmetry; the Li(+) ion lies on a
      special position with m.. site symmetry. Both bridging water mol-ecules have m2m
      site symmetry and both lattice water mol-ecules have m.. site symmetry; one of
      the latter was modelled with a site occupancy of 0.25. 

PMID- 24940216
TI  - Bis{MU-[(di-phenyl-phosphor-yl)meth-yl](phen-yl)bis-(1H-pyrazol-1
      yl)boranuido}dilithium.
AB  - The title compound, [Li2(C25H23BN4OP)2], features a centrosymmetric dimeric
      complex. The four-memberered Li2O2 ring is exactly planar due to symmetry. The Li
      atom is four-coordinated by two O atoms and by two N atoms of two different
      pyrazole rings. The dihedral angle between two pyrazole rings bonded to the same
      B atom is 45.66 (9) degrees . The B-N-N-Li-N-N metalla ring adopts a boat
      conformation. The crystal packing is stabilized by van der Waals inter-actions
      only. 

PMID- 24940215
TI  - Di-aqua-bis-(nicotinamide-kappaN (1))bis-(thiocyanato-kappaS)cobalt(II).
AB  - In the title compound, [Co(NCS)2(C6H6N2O)2(H2O)2], the Co(II) cation is located
      on an inversion centre and is coordinated by two thio-cyanate anions, two
      nicotinamide mol-ecules and two water mol-ecules in a distorted N2O2S2 octa
      hedral geometry. The amide group is twisted by 31.30 (16) degrees  with respect
      to the pyridine ring. In the crystal, mol-ecules are linked by O-H?O, O-H?S and N
      H?S hydrogen bonds into a three-dimensional supra-molecular network. Weak pi-pi
      stacking is observed between parallel pyridine rings of adjacent mol-ecules, the
      centroid-centroid distance being 3.8270 (19) A. 

PMID- 24940217
TI  - (1,6,7,12-Tetra-aza-perylene-kappa(2) N,N')bis-(4,4',5,5'-tetra-methyl-2,2'
      bipyridyl-kappa(2) N,N')ruthenium(II) bis-(hexa-fluorido-phosphate) aceto-nitrile
      tris-olvate.
AB  - In the title compound, rac-[Ru(C14H16N2)2(C16H8N4)](PF6)2.3C2H3N, discrete dimers
      of complex cations, [Ru(tmbpy)2-tape](2+), of opposite chirality are formed
      (tmbpy = tetra-methyl-bipyridine; tape = tetraazaperylene), held together by pi
      pi stacking inter-actions between the tetra-aza-perylene moieties with centroid
      centroid distances in the range 3.563 (3)-3.837 (3) A. These inter-actions
      exhibit a parallel displaced pi-pi stacking mode. Additional weak C-H?pi-ring and
      C-H?N and C-H?F inter-actions are found, leading to a three-dimensional
      architecture. The Ru(II) atom is coordinated in a distorted octa-hedral geometry.
      The counter-charge is provided by two hexa-fluorido-phosphate anions and the
      asymmetric unit is completed by three aceto-nitrile solvent mol-ecules of
      crystallization. Four F atoms of one PF6 (-) anion are disordered over three sets
      of sites with occupancies of 0.517 (3):0.244 (3):0.239 (3). Two aceto-nitrile
      solvent mol-ecules are highly disordered and their estimated scattering
      contribution was subtracted from the observed diffraction data using the SQUEEZE
      option in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]. 

PMID- 24940218
TI  - 2-[(Z)-1,1-Dioxo-2-(2,4,5-tri-fluoro-benz-yl)-3,4-di-hydro-2H-1,2-benzo-thia-zin
      4-yl-idene]acetic acid.
AB  - In the title compound, C17H12F3NO4S, the heterocyclic thia-zine ring adopts a
      half-chair conformation and the dihedral angle between the benzene rings is 43.28
      (9) degrees . The alpha,beta-unsaturated C=C group is inclined at an angle of
      21.0 (3) degrees  to the benzene ring of the benzo-thia-zine moiety. In the
      crystal, inversion dimers linked by pairs of carb-oxy-lic acid O-H?O hydrogen
      bonds generate R 2 (2)(8) loops. Each of the F atoms accepts a Ca-H?F (a =
      aromatic) hydrogen bond from an adjacent mol-ecule, resulting in (001) sheets. 

PMID- 24940219
TI  - 2-Hy-droxy-ethyl-ammonium iodide.
AB  - In the crystal structure of the title salt, C2H8NO(+).I(-), N-H?O, N-H?I and O
      H?I hydrogen bonds lead to the formation of layers staggered along the c axis. 

PMID- 24940220
TI  - (5E)-1-Benzyl-5-(3,3,3-tri-chloro-2-oxo-propyl-idene)pyrrolidin-2-one.
AB  - In the crystal structure of the title compound, C14H12Cl3NO2, no classical
      hydrogen-bonding inter-actions are observed. The methyl-ene fragments of the
      benzyl groups participate in non-classic hydrogen-bond inter-actions with the
      carbonyl O atoms of neighboring mol-ecules, generating co-operative
      centrosymmetric dimers with R 5 (5)(10) ring motifs. The overall mol-ecular
      arrangement in the unit cell seems to be highly influenced by secondary non
      covalent weak C-Cl?pi [Cl?Cg(phenyl ring) = 3.732 (2) A] and C-O?pi
      [O?Cg(pyrrolidine ring) = 2.985 (2) A] contacts. 

PMID- 24940221
TI  - N'-[(E)-2-Chloro-benzyl-idene]-2-(6-meth-oxy-naphthalen-2-yl)propano-hydrazide.
AB  - In the title compound, C21H19ClN2O2, the benzene ring and the naphthalene ring
      system are oriented at a dihedral angle of 65.24 (10) degrees . In the crystal, N
      H?O, C-H?N and C-H?O hydrogen bonds link the mol-ecules, forming chains along the
      b-axis direction. Further C-H?O hydrogen bonds link the chains, forming
      corrugated sheets lying parallel to (10-1). 

PMID- 24940222
TI  - Octyl (2E)-2-[2-(di-phenyl-phosphan-yl)benzyl-idene]hydrazinecarbodi-thio-ate.
AB  - The title compound, C28H33N2S2P, adopts the thione tautomeric form, as supported
      by the C-S distance [1.6744 (18) A]. The Schiff base exhibits an E conformation
      about the C=N bond but a Z conformation about the C-N bond. The terminal chain is
      disordered over two sets of sites with an occupancy ratio of 0.732 (3):0.268 (3).
      In the crystal, pairs of N-N-H hydrogen bonds between the thione groups link
      neighbouring mol-ecules into centrosymmetric dimers. 

PMID- 24940223
TI  - Buprenorphine.
AB  - In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4
      {systematic name: (2S)-2-[(5R,6R,7R,14S)-9alpha-cyclo-propyl-methyl-3-hy-droxy-6
      meth-oxy-4,5-ep-oxy-6,14-ethano-morphinan-7-yl]-3,3-di-methyl-butan-2-ol}, the
      cyclo-propyl-methyl group is disordered over two sites with an occupancy factor
      of 0.611 (3) for the major component. One of the hy-droxy groups is involved in
      intra-molecular O-H?O hydrogen bond. The other hy-droxy group acts as a proton
      donor in an inter-molecular O-H?O inter-action that connects mol-ecules into a
      zigzag chain along the b axis. 

PMID- 24940224
TI  - N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-di-hydro-1H-pyrazol-4-yl)-2-(4-nitro-phen
      yl)acetamide.
AB  - In the title compound, C19H18N4O4, the nitro-phenyl and phenyl rings are twisted
      by 67.0 (6) and 37.4 (4) degrees , respectively, with respect to the pyrazole
      ring plane [maximum deviation = 0.0042 (16) A]. The dihedral angle between the
      mean planes of the phenyl rings is 59.3 (3) degrees . The amide group, with a C-N
      C-C torsion angle of 177.54 (13) degrees , is twisted away from the plane of the
      pyrazole ring in an anti-periplanar conformation. In the crystal, N-H?O hydrogen
      bonds involving the carbonyl group on the pyrazole ring and the amide group,
      together with weak C-H?O inter-actions forming R 2 (2)(10) graph-set motifs, link
      the mol-ecules into chains along [100]. Additional weak C-H?O inter-actions
      involving the nitro-phenyl rings further link the mol-ecules along [001], also
      forming R 2 (2)(10) graph-set motifs, thereby generating (010) layers. 

PMID- 24940225
TI  - 2,3-Diphenyl-2,3-di-hydro-4H-pyrido[3,2-e][1,3]thia-zin-4-one.
AB  - In the racemic title compound, C19H14N2OS, the two phenyl substituents on the 1,3
      thia-zine ring are almost perpendicular to the pyridine ring which is fused to
      the thia-zine ring [inter-ring dihedral angles = 87.90 (8) and 85.54 (7) degrees
      ]. The dihedral angle between the two phenyl rings is 75.11 (7) degrees . The six
      membered thia-zine ring has an envelope conformation with the ortho-related C
      atom forming the flap. The crystals exhibit face-to-edge aromatic-ring
      interactions with the nearest C-H?C distance equal to 3.676 (3) A. 

PMID- 24940226
TI  - N,N'-(Propane-1,3-di-yl)dibenzo-thio-amide.
AB  - The title compound, C17H18N2S2, exhibits a trans-trans-trans-gauche(+) (tttg (+))
      conformation with regard to the NH-CH2-CH2-CH2-NH bond sequence. In the crystal,
      mol-ecules are connected by N-H?S=C and C-H?S=C hydrogen bonds, forming a
      herringbone arrangement along the c-axis direction. The two thioamide groups make
      dihedral angles of 43.0 (2) and 33.1 (2) degrees  with the adjacent phenyl rings.

PMID- 24940227
TI  - 4-Phenyl-1,2,4-tri-aza-spiro-[4.6]undec-1-ene-3-thione.
AB  - In the title compound, C14H17N3S, the plane of the phenyl ring makes a dihedral
      angle of 74.90 (4) degrees  with that of the tri-aza-thione ring (r.m.s.
      deviation = 0.001 A), while the seven-membered ring adopts a twist-chair
      conformation. No specific intermolecular interactions are discerned in the
      crystal packing. 

PMID- 24940228
TI  - 4-(Prop-2-yn-yl)-2H-1,4-benzo-thia-zin-3(4H)-one.
AB  - In the title compound, C11H9NOS, the six-membered heterocycle of the benzo-thia
      zine fragment exhibits a screw-boat conformation. The benzene ring makes a
      dihedral angle of 79.4 (1) degrees  with the mean plane through the prop-2-ynyl
      chain and the ring N atom. In the crystal, mol-ecules are linked by C-H?O inter
      actions of the acetyl-enic C-H group towards the carbonyl O atom of a
      neighbouring mol-ecule, forming zigzag chains running along the b-axis direction.

PMID- 24940229
TI  - 4-Aza-niumyl-2,2,6,6-tetra-methyl-piperidin-1-ium dinitrate.
AB  - In the crystal structure of the title salt, C9H22N2 (2+).2NO3 (-), the piperidine
      ring of the dication adopts a chair conformation and the orientation of the C-NH3
      bond is equatorial. The ions are linked by normal and bifurcated N-H?O hydrogen
      bonds in R 2 (2)(6), two R 4 (2)(8) and R 3 (4)(14) graf-set motifs, generating a
      three-dimensional network. 

PMID- 24940230
TI  - 3-Chloro-2-methyl-anilinium chloride monohydrate.
AB  - In the title hydrated salt, C7H9ClN(+).Cl(-).H2O, the organic cations, anions and
      water mol-ecules are connected by N-H?Cl, N-H?O and O-H?Cl hydrogen bonds. These
      inter-actions lead to the formation of layers parallel to the ac plane. 

PMID- 24940231
TI  - 2-[(1-Oxidopyridin-4-yl)sulfan-yl]benzoic acid.
AB  - In the title compound, C12H9NO3S, the dihedral angle between the pyridine and
      benzene rings is 83.93 (7) degrees . In the crystal, pairs of O-H?O hydrogen
      bonds link the molecules, forming inversion dimers with graph-set notation R 2
      (2)(22). These dimers are in turn linked by weak C-H?O hydrogen bonds along
      [100], forming R 2 (2)(8) rings. 

PMID- 24940232
TI  - A new polymorph of N-(2-{N'-[(1E)-2-hy-droxy-benzyl-idene]hydrazinecarbon-yl}phen
      yl)benzamide.
AB  - The title compound, C21H17N3O3, is a new polymorph of an already published
      structure [Shashidhar et al. (2006 ?). Acta Cryst. E62, o4473-o4475]. The
      previously reported structure crystallizes in the monoclinic space group C2/c,
      whereas the structure reported here is in the tetra-gonal space group I41/a. The
      bond lengths and angles are similar in both structures. The mol-ecule adopts an
      extended conformation via intra-molecular N-H?O and O-H?N hydrogen bonds; the
      terminal phenyl ring and the hy-droxy-lphenyl ring are twisted with respect to
      the central benzene ring by 44.43 (7) and 21.99 (8) degrees , respectively. In
      the crystal, mol-ecules are linked by N-H?O hydrogen bonds, weak C-H?O hydrogen
      bonds and weak C-H?pi inter-actions into a three-dimensional supra-molecular
      network. 

PMID- 24940233
TI  - (Z)-1-[(2E)-3,4-Diphenyl-2,3-di-hydro-1,3-thia-zol-2-yl-idene]-2-[1-(4-hy-droxy
      phen-yl)ethyl-idene]hydrazinium bromide including an unknown solvate.
AB  - In the title compound, C23H20N3OS(+).Br(-), the di-hydro-thia-zole ring (r.m.s.
      deviation = 0.015 A) is twisted with respect to each of the C- and N-bound phenyl
      rings and the hy-droxy-benzene ring, making dihedral angles of 76.0 (2), 71.2 (2)
      and 9.8 (2) degrees , respectively. In the crystal, inversion-related mol-ecules
      are linked by association of the bromide ions with the cations via N-H?Br and O
      H?Br hydrogen-bonding inter-actions. These mol-ecules run in channels parallel to
      the a axis through face-to-face pi-pi stacking inter-actions between the hy-droxy
      benzene rings [centroid-centroid distances = 3.785 (3) A] which, in turn, are
      connected into layers parallel to (110) by weak C-H?pi inter-actions. A small
      region of electron density well removed from the main mol-ecule and appearing
      disordered over a center of symmetry was removed with PLATON SQUEEZE [Spek (2009
      ?). Acta Cryst. D65, 148-15] following unsuccessful attempts to model it as
      plausible solvent molecule. The nature of the solvent was not known and hence,
      this is not taken into account when calculating M r and related data. 

PMID- 24940234
TI  - 5-(4-Hy-droxy-phen-yl)imidazolidine-2,4-dione.
AB  - The title compound, C9H8N2O3, was prepared by reaction of phenol, glyoxylic acid
      and urea in water. The imidazolidine ring adopts an almost planar conformation
      (r.m.s. deviation = 0.012 A) and is twisted by 89.3 (1) degrees  relative to the
      benzene ring. In the crystal, mol-ecules are linked by N-H?O and O-H?O hydrogen
      bonds into a three-dimensional framework. 

PMID- 24940235
TI  - 3-Iodo-1H-pyrazolo-[3,4-b]pyridine.
AB  - The title compound, C6H4IN3, is essentially planar, with a dihedral angle of 0.82
      (3) degrees  between the planes of the pyridine and pyrazole rings. In the
      crystal, pairs of mol-ecules are connected into inversion dimers through N-H?N
      hydrogen bonds. C-I?N halogen bonds link the dimers into zigzag chains parallel
      to the b-axis direction. The packing also features pi-pi stacking inter-actions
      along (110) with inter-planar distances of 3.292 (1) and 3.343 (1) A, and
      centroid-centroid distances of 3.308 (1) and 3.430 (1) A. 

PMID- 24940236
TI  - De-acetyl-cinobufalactam monohydrate.
AB  - The title compound, C24H33NO4.H2O, the reaction product of de-acetyl-cinobufagin
      with ammonium acetate, consists of three cyclo-hexane rings (A, B and C), one
      five-membered ring (D), one six-membered lactone ring (E) and an epoxide ring
      (F). The stereochemistry of the ring junctures are A/B cis, B/C trans, C/D cis
      and D/F cis. Cyclo-hexane rings A, B and C have normal chair conformations. The
      five-membered ring D adopts an envelope conformation (with the C atom bearing the
      lactone ring as the flap) and the lactone ring E is planar. In the crystal, hy
      droxy and water O-H?O and amine N-H?O hydrogen bonds involving carbonyl, hy-droxy
      and water O-atom acceptors link the mol-ecules into a three-dimensional network. 

PMID- 24940237
TI  - N-(1-Allyl-3-chloro-4-eth-oxy-1H-indazol-5-yl)-4-methyl-benzene-sulfonamide.
AB  - In the title compound, C19H20ClN3O3S, the benzene ring is inclined to the
      indazole ring system by 51.23 (8) degrees . In the crystal, mol-ecules are linked
      by pairs of N-H?O hydrogen bonds, forming inversion dimers which stack in columns
      parallel to [011]. The atoms in the allyl group are disordered over two sets of
      sites with an occupancy ratio of 0.624 (8):0.376 (8). 

PMID- 24940238
TI  - 1-[4-Bromo-2-(tri-fluoro-meth-oxy)phen-yl]-3-methyl-1H-1,2,4-triazole.
AB  - In the title compound, C10H7BrF3N3O, the dihedral angle between the benzene and
      triazole rings is 23.17 (12) degrees  and the C atom of the -CF3 group deviates
      from its attached ring plane by 1.147 (3) A. In the crystal, mol-ecules are
      linked by C-H?N inter-actions, generating C(7) chains running along [010]. 

PMID- 24940239
TI  - Diethyl 7,7'-di-chloro-4-oxo-4H-[1,4'-bi-quinoline]-3,3'-di-carboxyl-ate.
AB  - In the title compound, C24H18Cl2N2O5, the quinoline and quinolinone moieties are
      nearly perpendicular to each other, forming a dihedral angle of 82.36 (3) degrees
      . In the crystal, mol-ecules form a halogen bond between a Cl atom of a
      quinolinone moiety and the N atom of the quinoline moiety of the inversion
      equivalent [Cl?N = 3.106 (3) A]. The mol-ecules also form two kinds of C-H?O
      hydrogen-bonded centrosymmetric inversion dimers, making chains along the c-axis
      direction which are further inter-linked by the halogen bonds into layers
      parallel to the bc plane. 

PMID- 24940240
TI  - 2-Meth-oxy-4-(2-meth-oxy-phen-yl)-5,6,7,8,9,10-hexa-hydro-cyclo-octa-[b]pyridine
      3-carbo-nitrile.
AB  - In the title compound, C20H22N2O2, the central pyridine ring forms a dihedral
      angle of 76.32 (8) degrees  with the pseudo-axial benzene ring. The cyclo-octane
      ring adopts a twisted boat chair conformation. In the crystal, weak inter
      molecular C-H?pi inter-actions between inversion-related mol-ecules result in the
      formation of linear double chains along the b-axis direction. 

PMID- 24940241
TI  - 9-Amino-acridin-10-ium 4-amino-benzo-ate dihydrate.
AB  - The asymmetric unit of the title hydrated salt, C13H11N2 (+).C7H6NO2 (-).2H2O,
      consists of two independent 9-amino-acridinium cations, two 4-amino-benzoate
      anions and four water mol-ecules. Both 9-amino-acridinium cations are essentially
      planar, with maximum deviations of 0.034 (1) and 0.025 (2) A, and are protonated
      at the pyridine N atoms. The 4-amino-benzoate anions are approximately planar,
      with dihedral angles of 9.16 (19) and 5.4 (2) degrees  between the benzene ring
      and the carboxyl-ate group. In the crystal, the two independent anions are
      connected by N-H?O hydrogen bonds, forming a layer parallel to (100). The layers
      are connected through the cations by N-H?N and N-H?O hydrogen bonds. The water
      mol-ecules, which form O-H?O hydrogen-bonded chains along the b-axis direction,
      connect the anions and the cations by O-H?O, N-H?O and C-H?O hydrogen bonds. The
      crystal structure also features pi-pi inter-actions [centroid-centroid distances
      = 3.6343 (9)-3.8366 (10) A] and a C-H?pi inter-action. 

PMID- 24940242
TI  - 2-(2-Fluoro-phen-yl)-5-iodo-7-methyl-3-methyl-sulfinyl-1-benzo-furan.
AB  - In the title compound, C16H12FIO2S, the dihedral angle between the plane of the
      benzo-furan ring system (r.m.s. deviation = 0.023 A) and that of the 2-fluoro
      phenyl ring is 39.78 (7) degrees . In the crystal, mol-ecules are linked via
      pairs of I?pi contacts [3.812 (2) A] and a pi-pi inter-action between the benzene
      rings of neighbouring mol-ecules [centroid-centroid distance = 3.821 (2) A] into
      inversion dimers. These dimers are further linked by pi-pi inter-actions between
      the furan and benzene rings of neighbouring mol-ecules [centroid-centroid
      distance = 3.668 (2) A]. The mol-ecules stack along the a-axis direction. In
      addition, C-H?O hydrogen bonds are observed between inversion-related dimers. 

PMID- 24940243
TI  - N-(2-Formyl-phen-yl)-4-methyl-N-[(4-methyl-phen-yl)sulfon-yl]benzene-sulfon
      amide.
AB  - In the title compound, C21H19NO5S2, the dihedral angles between the formyl-phenyl
      ring and the two methyl-phenyl rings are 29.3 (3) and 28.9 (3) degrees ,
      respectively; the dihedral angle between the methyl-phenyl rings is 48.4 (2)
      degrees . The C-N-S-C torsion angles are -74.1 (2) and -105.4 (2) degrees . In
      the crystal, molecules are linked by pairs of C-H?O hydrogen bonds, forming
      inversion dimers. 

PMID- 24940244
TI  - Ethyl 5-oxo-4-phenyl-5,6-di-hydro-4H-1,3,4-oxadiazine-2-carboxyl-ate.
AB  - The asymmetric unit of title compound, C12H12N2O4, consists of two independent
      mol-ecules. In each mol-ecule, the oxadiazine ring has a flattened envelope
      conformation with the methyl-ene C atom as the flap atom, and the eth-oxy
      carbonyl unit is in a syn-periplanar conformation with respect to the oxadiazine
      ring as indicated by O-C-C=O torsion angles of 1.9 (4) and 2.5 (4) degrees . The
      dihedral angles between the mean plane of the oxadiazine ring and the phenyl ring
      are 80.07 (13) and 42.98 (14) degrees . In the crystal, mol-ecules are linked by
      C-H?O hydrogen bonds and stacked in a double-column along the a-axis direction. 

PMID- 24940245
TI  - 1-Deacet-oxy-1-oxocaesalmin.
AB  - The title compound, C24H30O7, is a diterpenoid isolated from the seeds of
      Caesalpinia minax. It consists of two cyclo-hexane rings (A and B), one
      unsaturated six-membered ring (C) and one furan ring (D). The stereochemistry of
      the ring junctures is A/B trans and B/C trans. Rings A and B have normal chair
      conformations while C adopts a twisted half-chair conformation due to fusion to
      the furan ring which is planar [r.m.s. deviation = 0.0009 (2) A]. In the crystal,
      hydroxyl O-H?Ocarbon-yl hydrogen bonds link the mol-ecules into a chain structure
      extending along the a-axis direction. 

PMID- 24940246
TI  - 9-(3-Bromo-5-chloro-2-hy-droxy-phen-yl)-10-(2-hy-droxy-eth-yl)-3,6-diphenyl
      3,4,9,10-tetra-hydro-acridine-1,8(2H,5H)-dione.
AB  - In the title compound, C33H27BrClNO4, the di-hydro-pyridine ring adopts a
      flattened boat conformation. The mol-ecular conformation is stabilized by an
      intra-molecular O-H?O hydrogen bond, with an S(8) ring motif. In the crystal, O
      H?O, C-H?O and C-H?Cl hydrogen bonds, and C-H?pi inter-actions link the mol
      ecules, forming a three-dimensional network. In the acridinedione ring system,
      the two ring C atoms at the 2- and 3-positions, and the C atom at the 6-position
      and the atoms of the phenyl ring attached to the C atom at the 6-position are
      disordered over two sets of sites with occupancy ratios of 0.783 (5):0.217 (5)
      and 0.526 (18):0.474 (18), respectively. 

PMID- 24940247
TI  - 7,7-[Ethane-1,2-diylbis(oxy)]-2-[hydroxy(phenyl)methyl]bicyclo[3.3.1]nonan-3-one.
AB  - In the title compound, C18H22O4, the cyclo-hexane and cyclo-hexa-none rings adopt
      normal chair and half-chair conformations, respectively. The dioxolane ring is
      almost planar, with an r.m.s. deviation of 0.094 (3) A. In the crystal, mol
      ecules are connected by O-H?O hydrogen bonds, forming 21 helical chains along the
      a-axis direction. The chains are further connected by C-H?O hydrogen bonds. 

PMID- 24940248
TI  - 2-(5-Iodo-2-oxoindolin-3-yl-idene)hydrazinecarbo-thio-amide including an unknown
      solvate.
AB  - The mol-ecule of the title compound, C9H7IN4OS, is almost planar (r.m.s.
      deviation = 0.0373 A). In the mol-ecule, N-H?N and N-H?O hydrogen bonds generate,
      respectively, S(5) and S(6) ring motifs. In the crystal, mol-ecules are linked
      via N-H?O hydrogen bonds, forming chains propagating along [010]. These chains
      are linked via S?I contacts [3.4915 (16) A], forming sheets lying parallel to
      (100). A region of disordered electron density, probably a disordered tetra-hydro
      furan solvent mol-ecule, was treated using the SQUEEZE routine in PLATON [Spek
      (2009). Acta Cryst. D65, 148-155]. The formula mass and unit-cell characteristics
      were not taken into account during refinement. 

PMID- 24940249
TI  - 2-Phenyl-5,6,7,8-tetra-hydro-imidazo[2,1-b][1,3]benzo-thia-zole.
AB  - The title compound, C15H14N2S, crystallizes with two independent mol-ecules in
      the asymmetric unit. The central imidazo[2,1-b][1,3]benzo-thia-zole unit is
      planar (r.m.s. deviations of 0.010 and 0.008 A for the two independent mol
      ecules). The fused tetra-hydro-hexane ring adopts a half-chair conformation. The
      phenyl substituent is twisted by 16.96 (13) and 22.89 (12) degrees  relative to
      the central imidazo[2,1-b][1,3]benzo-thia-zole unit in the two mol-ecules. In the
      crystal, there are no significant intermolecular interactions present. 

PMID- 24940250
TI  - (2E)-4-(4-Bromo-phen-yl)-2-{2-[(1E)-cyclo-pentyl-idene]hydrazin-1-yl-idene}-3
      phenyl-2,3-di-hydro-1,3-thia-zole.
AB  - In the title compound, C20H18BrN3S, the cyclo-pentane ring adopts a half-chair
      conformation. The 4-bromo-phenyl and phenyl rings make dihedral angles of 34.6
      (1) and 68.52 (6) degrees , respectively, with the di-hydro-thia-zole ring. In
      the crystal, the mol-ecules pack in sheets approximately parallel to (101) which
      are formed by weak C-H?Br inter-actions. 

PMID- 24940251
TI  - N'-[(E)-3-Bromo-5-chloro-2-hy-droxy-benzyl-idene]furan-2-carbohydrazide.
AB  - In the title compound, C12H8BrClN2O3, the furan ring makes a dihedral angle of
      17.2 (2) degrees  with the six-membered ring. An intra-molecular O-H?N hydrogen
      bond stabilizes the mol-ecular conformation. In the crystal, N-H?O hydrogen bonds
      connect the mol-ecules into chains running along the c-axis direction. The
      crystal packing is additionally stabilized by C-H?O inter-actions into a three
      dimensional supramolecular architecture. 

PMID- 24940252
TI  - 1-Cyclo-hexyl-6,7-dimeth-oxy-1,4-di-hydro-naphthalene.
AB  - The title compound, C18H24O2, was isolated from the leaves extract of Ficus
      carica L. The cyclo-hexane ring displays a chair conformation whereas the cyclo
      hexa-1,4-diene ring adopts a flattened boat conformation with methyl C atoms at
      the prow and stern. In the crystal, mol-ecules are linked by weak C-H?O hydrogen
      bonds into supra-molecular chains propagated along the b-axis direction. 

PMID- 24940253
TI  - Ethyl 5-methyl-7-phenyl-1,2,4-triazolo[4,3-a]pyrimidine-6-carboxyl-ate.
AB  - In the title compound, C15H14N4O2, the triazolo-pyrimidine ring system is almost
      planar (r.m.s. deviation = 0.02 A) and the phenyl ring is inclined to its mean
      plane by 42.45 (9) degrees . The carboxyl group is inclined to the triazolo
      pyrimidine ring mean plane by 57.8 (3) degrees . In the mol-ecule, there is a
      short C-H?O contact involving the carbonyl O atom and an H atom of the adjacent
      methyl substituent. In the crystal, neighbouring mol-ecules are linked by C-H?O
      hydrogen bonds, forming chains propagating along [010]. There are also weak pi-pi
      inter-actions present involving the pyridine and phenyl rings of neighbouring
      chains [inter-centroid distance = 3.8580 (16) A]. 

PMID- 24940255
TI  - 1-(4-Chloro-butano-yl)-3-(3-chloro-phen-yl)thio-urea.
AB  - The two independent mol-ecules in the asymmetric unit of the title compound,
      C11H12Cl2N2OS, exhibit different conformations, with the benzene ring and the
      N2CS thio-urea group forming dihedral angles of 87.40 (18) and 69.42 (15) degrees
      . An intra-molecular N-H?O hydrogen bond is present in each mol-ecule. Two
      further N-H?O hydrogen bonds link the independent mol-ecules into a dimer. In the
      crystal, the dimers are linked by N-H?S and C-H?S hydrogen bonds, forming chains
      parallel to the c axis. 

PMID- 24940254
TI  - tert-Butyl N-[2-(N-isobutyl-4-meth-oxy-benzene-sulfonamido)-eth-yl]carbamate.
AB  - The title compound, C18H30N2O5S, was synthesized by the reaction of tert-butyl 2
      (iso-butyl-amino)-ethyl-carbamate with p-meth-oxy-phenyl-sulfonyl chloride. In
      the mol-ecule, two intra-molecular C-H?O hydrogen bonds are observed. In the
      crystal, mol-ecules are linked by N-H?O hydrogen bonds involving the imino group
      N atom and the ester group O atom into chains running parallel to the b axis. The
      chains are further connected by C-H?O hydrogen bonds, forming layers parallel to
      the bc plane. 

PMID- 24940256
TI  - Zwitterionic 1-{(E)-[(2-methyl-phen-yl)iminium-yl]meth-yl}naphthalen-2-olate.
AB  - The title Schiff base, C18H15NO, crystallizes in its zwitterionic form and an N
      H?O hydrogen bond closes an S(6) ring. The dihedral angle between the aromatic
      ring systems is 36.91 (10) degrees . Weak aromatic pi-pi stacking occurs in the
      crystal [minimum centroid-centroid separation = 3.7771 (15) A]. 

PMID- 24940257
TI  - 9-Allyl-9H-fluoren-9-ol.
AB  - The asymmetric unit of the title compound, C16H14O, contains two independent mol
      ecules differing in the orientations of the allyl groups; the corresponding O-C
      C(H2)-C(H) torsion angles are -61.01 (13) and -177.43 (10) degrees . In the
      crystal, O-H?O hydrogen bonds link four mol-ecules into a centrosymmetric tetra
      mer, in which each hy-droxy group acts as a donor and an acceptor of hydrogen
      bonds. 

PMID- 24940258
TI  - 2,4-Di-tert-butyl-6-({[2-(di-methyl-amino)-eth-yl](2-hy-droxy-benz-yl)amino}-meth
      yl)phenol.
AB  - The title compound, C26H40N2O2, has both its N atoms in trigonal-pyramidal
      geometries. The mol-ecular structure is stabilized by O-H?N and C-H?O hydrogen
      bonds. In the crystal, C-H?pi inter-actions lead to the formation of a
      supramolecular helical chain along the b-axis direction. 

PMID- 24940259
TI  - N-(3-Chloro-4-eth-oxy-1-methyl-1H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.
AB  - The indazole ring system of the title compound, C17H18ClN3O4S, is almost planar
      (r.m.s. deviation = 0.0113 A) and forms dihedral angles of 32.22 (8) and 57.5 (3)
      degrees  with the benzene ring and the mean plane through the 4-eth-oxy group,
      respectively. In the crystal, mol-ecules are connected by pairs of N-H?O hydrogen
      bonds into inversion dimers, which are further linked by pi-pi inter-actions
      between the diazole rings [inter-centroid distance = 3.4946 (11) A], forming
      chains parallel to [101]. 

PMID- 24940260
TI  - 2-Benzoyl-4-chloro-aniline thio-semi-carbazone.
AB  - In the title compound, C14H13ClN4S, obtained from a reaction of 2-benzoyl-4
      chloro-aniline with thio-semicarbazide in ethanol, the dihedral angle between the
      aromatic rings is 81.31 (13) degrees . In the crystal, the mol-ecules are linked
      by three N-H?S hydrogen bonds, forming centrosymmetric rings with set-graph motif
      R 2 (2)(8) and R 2 (2)(18), and resulting in the formation of a two-dimensional
      network lying parallel to (010). 

PMID- 24940261
TI  - Flunarizinium isonicotinate.
AB  - In the cation of the title salt {systematic name: 4-[bis-(4-fluoro-phen-yl)meth
      yl]-1-[(2E)-3-phenyl-prop-2-en-1-yl]piperazin-1-ium pyridine-4-carboxyl-ate},
      C26H27F2N2 (+).C6H4NO2 (-), the piperazine ring is in a slightly distorted chair
      conformation. The dihedral angle between the mean planes of the fluoro
      substituted benzene rings is 81.9 (1) degrees  and these benzene rings form
      dihedral angles of 6.5 (1) and 87.8 (1) degrees  with the phenyl ring. In the
      crystal, a single N-H?O hydrogen bond links the cation and the anion. In
      addition, weak C-H?O hydrogen bonds and pi-pi stacking inter-actions involving
      one of the fluoro-substituted benzene rings and the phenyl ring, with a centroid
      centroid distance of 3.700 (7) A, link mol-ecules along [100]. 

PMID- 24940262
TI  - Pyrimethaminium 2-{[4-(tri-fluoro-meth-yl)phen-yl]sulfan-yl}benzoate dimethyl
      sulfoxide monosolvate.
AB  - In the cation of the title solvated mol-ecular salt, C12H14ClN4 (+).C14H8F3O2S(
      ).C2H6OS [systematic name of the cation: 2,4-di-amino-5-(4-chloro-phen-yl)-6
      ethyl-pyrimidin-1-ium], the dihedral angle between the planes of the pyrimidinium
      and 4-chloro-phenyl rings is 77.2 (5) degrees . In the anion, the planes of the
      benzene rings are twisted with respect to each other by 71.5 (5) degrees .
      Disorder was modelled for the dimethyl sulfoxide solvent mol-ecule over two set
      of sites in a 0.7487 (13):0.2513 (13) ratio. In the crystal, the cations are
      linked by inversion-generated pairs of N-H?N hydrogen bonds, with an R 2 (2)(8)
      graph-set motif. The cation donates two N-H?O hydrogen bonds to the anion, also
      generating an R 2 (2)(8) loop. These inter-actions, along with cation-solvent N
      H?O hydrogen bonds, and cation-anion C-H?F, solvent-anion C-H?O and C-H?F inter
      actions, result in a three-dimensional network. 

PMID- 24940263
TI  - 1-(4-Bromo-phen-yl)-3-(3-chloro-propan-oyl)thio-urea.
AB  - The title compound, C10H10BrClN2OS, adopts a trans-cis conformation with respect
      to the position of the 3-chloro-propanoyl and 4-bromo-phenyl groups,
      respectively, against the thiono C=S bond across their C-N bonds. The benzene
      ring makes a dihedral angle of 9.55 (16) degrees  with the N2CS thio-urea moiety.
      Intra-molecular N-H?O and C-H?S hydrogen bonds occur. In the crystal, mol-ecules
      are linked into chains along the c-axis direction by N-H?S, C-H?S and C-H?O
      hydrogen bonds. 

PMID- 24940264
TI  - (2Z)-2-Benzyl-idene-4-n-butyl-3,4-di-hydro-2H-1,4-benzo-thia-zin-3-one.
AB  - In the title compound, C19H19NOS, the six-membered hetero-cyclic ring of the
      benzo-thia-zine fragment exhibits a screw boat conformation. The plane of the
      fused benzene ring makes a dihedral angle of 72.38 (12) degrees  with that of the
      terminal phenyl ring, and is nearly perpendicular to the mean plane formed by the
      atoms through the n-butyl chain, as indicated by the dihedral angle of 88.1 (2)
      degrees . In the crystal, mol-ecules are linked by C-H?O inter-actions to form
      supra-molecular chains along [110]. 

PMID- 24940265
TI  - 1,3-Bis(3-tert-butyl-2-hy-droxy-5-meth-oxy-benz-yl)hexa-hydro-pyrimidin-5-ol
      monohydrate.
AB  - The asymmetric unit of the title compound, C28H42N2O5.H2O, consists of one half
      of the organic mol-ecule and one half-mol-ecule of water, both of which are
      located on a mirror plane which passes through the central C atoms and the
      hydroxyl group of the heterocyclic system. The hydroxyl group at the central ring
      is disordered over two equally occupied positions. The six-membered ring adopts a
      chair conformation, and the 2-hy-droxy-benzyl substituents occupy the sterically
      preferred equatorial positions. The aromatic rings make dihedral angles of 75.57
      (9) degrees  with the mean plane of the heterocyclic ring. The dihedral angle
      between the two aromatic rings is 19.18 (10) degrees . The mol-ecular structure
      features two intra-molecular phenolic O-H?N hydrogen bonds with graph-set motif
      S(6). In the crystal, mol-ecules are connected via O-H?O hydrogen bonds into
      zigzag chains running along the a-axis direction. 

PMID- 24940266
TI  - 2,4,6-Tri-nitro-phenyl 3-bromo-benzoate.
AB  - In the title picryl-substituted ester, C13H6BrN3O8, the mean plane of the central
      ester C-O-C(=O)-C fragment (r.m.s. deviation= 0.0186 A) is rotated by 84.73 (7)
      degrees  and 19.92 (12) degrees  to the picryl and phenyl rings, respectively. In
      the crystal, the mol-ecules are linked by C-H?O inter-actions, forming
      centrosymmetric dimers enclosing R (2) 2(10) and R (2) 2(22) ring motifs along
      [001] and further helical chains of dimers enclosing R (2) 2(10) ring motifs
      along [010]. 

PMID- 24940267
TI  - 5-Cyclo-hexyl-2-methyl-3-(3-methyl-phenyl-sulfin-yl)-1-benzo-furan.
AB  - In the title compound, C22H24O2S, the cyclo-hexyl ring adopts a chair
      conformation. The dihedral angle between the mean planes of the benzo-furan and 3
      methyl-phenyl moieties is 86.48 (4) degrees . In the crystal, mol-ecules are
      connected along the a-axis direction by two different inversion-generated pairs
      of C-H?pi and C-H?O inter-actions. 

PMID- 24940268
TI  - 1,1,1-Tris(di-methyl-amino)-2-[tris-(di-methyl-amino)-phospho-ranyl
      idene]diphosphinium tetra-phenyl-borate tetra-hydro-furan monosolvate.
AB  - In the tetra-hydro-furan solvate of the title salt, C12H36N6P3 (+).C24H20B(
      ).C4H8O, the cation features short P-P bond lengths [2.1111 (11) and 2.1364 (10)
      A] and a distinctly bent P-P-P angle [104.67 (4) degrees ] that confirm that the
      mol-ecule is not allene-like. In the crystal, the solvent mol-ecule is linked to
      the cation via a weak C-H?O hydrogen bond. 

PMID- 24940269
TI  - 3-(4-Bromo-phen-yl)cyclo-pent-2-en-1-one.
AB  - In the title compound, C11H9BrO, the cyclo-pentenone ring is almost planar with
      an r.m.s. deviation of 0.0097 A. The largest inter-ring torsion angles [2.4 (3),
      1.3 (3) and 3.53 (2) degrees ] reveal only a very small twist between the rings,
      and suggest that the two rings are conjugated. The mol-ecule is slightly bowed,
      as shown by the small dihedral angle between the rings [5.3 (1) degrees ]. The
      crystal packing pattern consists of parallel sheets that stack parallel to the ac
      plane. Each sheet consists of mol-ecules that pack side-to-side with the same
      relative orientation of phenyl and cyclo-pentenone rings along the a- and c-axis
      directions. Slipped side-to-side, face-to-face and edge-to-face inter-actions
      exist between pairs of sheets with edge-to-edge and edge-to-face O?H-C(sp (2))
      weak hydrogen-bond contacts. A relatively short edge-to-face contact (2.77 A)
      also exists between pairs of sheets. 

PMID- 24940270
TI  - 1-[Bis(4-fluoro-phen-yl)meth-yl]-4-[(2Z)-3-phenyl-prop-2-en-1-yl]piperazine-1,4
      diium dichloride hemihydrate.
AB  - The asymmetric unit of the title monohydrated salt, 2C26H28F2N2 (2+).4Cl(-.)H2O,
      consists of a 1-[bis-(4-fluoro-phen-yl)meth-yl]-4-[(2Z)-3-phenyl-prop-2-en-1
      yl]piperazine-1,4-diium cation with a diprotonated piperizine ring in close
      proximity to two chloride anions and a single water mol-ecule that lies on a
      twofold rotation axis. In the cation, the piperazine ring adopts a slightly
      distorted chair conformation. The dihedral angles between the phenyl ring and the
      4-fluoro-phenyl rings are 89.3 (9) and 35.0 (5) degrees . The two fluoro-phenyl
      rings are inclined at 65.0 (5) degrees  to one another. In the crystal, N-H?Cl
      hydrogen bonds and weak C-H?Cl inter-molecular inter-actions link the mol-ecules
      into chains along [010]. In addition, weak C-H?O inter-actions between the
      piperizine and prop-2-en-1-yl groups with the water mol-ecule, along with weak C
      H?Cl inter-actions between the prop-2en-1-yl and methyl groups with the chloride
      ions, weak C-H?F inter-actions between the two fluoro-phenyl groups and weak O
      H?Cl inter-actions between the water mol-ecule and chloride ions form a three
      dimensional supra-molecular network. 

PMID- 24940271
TI  - 6-(Hex-5-en-yloxy)naphthalene-2-carb-oxy-lic acid.
AB  - The asymmetric unit of the title compound, C17H18O3, comprises three independent
      mol-ecules with similar geometries. In each mol-ecule, the carbonyl group is
      twisted away from the napthalene ring system, making dihedral angles of 1.0 (2),
      1.05 (19) degrees  and 1.5 (2) degrees . The butene group in all three mol-ecules
      are disordered over two sets of sites, with a refined occupancy ratio of 0.664
      (6):0.336 (6). In the crystal, mol-ecules are oriented with respect to their
      carbonyl groups, forming head-to-head dimers via O-H?O hydrogen bonds. Adjacent
      dimers are further inter-connected by C-H?O hydrogen bonds into chains along the
      a-axis direction. The crystal structure is further stabilized by weak C-H?pi
      inter-actions. 

PMID- 24940272
TI  - 2,3,5,6-Tetra-fluoro-1,4-bis-({[(5-methyl-thio-phen-2-yl)methyl-idene]amino}-meth
      yl)benzene.
AB  - The title compound, C20H16F4N2S2, is a flexible bis-thio-phene-type Schiff base
      ligand with a perfluorinated backbone. The terminal thio-phene rings are almost
      normal to one another with a dihedral angle of 83.8 (2) degrees , and they are
      tilted to the central tetra-fluorinated benzene ring with dihedral angles of 61.2
      (2) and 77.7 (1) degrees . In the crystal, there are pi-pi inter-actions
      involving the benzene ring and the thiophene ring of a symmetry-related molecule
      with a centroid-centroid separation of 3.699 (3) A. 

PMID- 24940273
TI  - A third polymorph of 1,4-bis-(1H-benzimid-azol-2-yl)benzene.
AB  - The title compound, C20H14N4, is a new polymorph of the previously reported
      structures, which were ortho-rhom-bic, space group Pbca [Bei et al. (2000). Acta
      Cryst. C56, 718-719] and monoclinic, space group P21/c [Dudd et al. (2003). Green
      Chem. 5, 187-192]. The asymmetric unit consists of two independent mol-ecules in
      which the dihedral angels between the central benzene ring and the outer
      benzimidazole ring systems are 16.81 (10) and 14.23 (10) degrees  in one molecule
      and 26.09 (10) and 37.29 (10) degrees  in the other. In the crystal, mol-ecules
      are linked by N-H?N and C-H?N hydrogen bonds into a tape running along the c-axis
      direction. 

PMID- 24940274
TI  - 4-(Furan-2-carbon-yl)piperazin-1-ium 3,5-di-nitro-benzoate.
AB  - In the cation of the title salt, C9H13N2O2 (+).C7H3N2O6 (-), the piperazine ring
      adopts a slightly distorted chair conformation. Twofold rotational disorder is
      exhibited by the furan ring in a 0.430 (4):0.570 (4) ratio. In the crystal, N-H?O
      hydrogen bonds link the ions into chains along [010]. Additional weak C-H?O inter
      actions are observed, leading to a supra-molecular layer parallel to (011). 

PMID- 24940275
TI  - 4-(Pyrimidin-2-yl)piperazin-1-ium (E)-3-carb-oxy-prop-2-enoate.
AB  - In the cation of the title salt, C8H13N4 (+).C4H3O4 (-), the piperazinium ring
      adopts a slightly distorteded chair conformation. In the crystal, a single strong
      O-H?O inter-molecular hydrogen bond links the anions, forming chains along the c
      axis direction. The chains of anions are linked by the cations, via N-H?O
      hydrogen bonds, forming sheets parallel to (100). These layers are linked by weak
      C-H?O hydrogen bonds, forming a three-dimensional structure. In addition, there
      are weak pi-pi inter-actions [centroid-centroid distance = 3.820 (9) A] present
      involving inversion-related pyrimidine rings. 

PMID- 24940276
TI  - 1-(2-Bromo-4-chloro-phen-yl)-3,3-di-methyl-thio-urea.
AB  - In the title compound, C9H10BrClN2S, the di-methyl-thio-urea group is twisted
      from the benzene ring plane by 54.38 (6) degrees . In the crystal, the amino
      groups are involved in the formation of N-H?S hydrogen bonds, which link the mol
      ecules into chains along [010]. Weak C-H?Cl inter-actions further link these
      chains into layers parallel to the ab plane. 

PMID- 24940277
TI  - 3-[3-(2-Fluoro-benzo-yl)thio-ureido]propionic acid.
AB  - In the title compound, C10H11FN3O3S, the 2-fluoro-benzoyl and proponic acid
      groups maintain a trans-cis conformation with respect to the thiono C=S bond
      across their C-N bonds. The propionic acid group adopts an anti conformation
      about the C-C bond, with an N-C-C-C torsion angle of 173.8 (2) degrees . The
      amino groups are involved in the formation of intra-molecular N-H?O and N-H?F
      hydrogen bonds. In the crystal, pairs of O-H?O hydrogen bonds link mol-ecules
      into inversion dimers. 

PMID- 24940278
TI  - 5-Chloro-2-(2-fluoro-phen-yl)-7-methyl-3-methyl-sulfinyl-1-benzo-furan.
AB  - In the title compound, C16H12ClFO2S, the dihedral angle between the mean planes
      of the benzo-furan and 2-fluoro-phenyl rings is 34.85 (6) degrees . In the
      crystal, mol-ecules are linked via pairs of C-H?O hydrogen bonds, forming zigzag
      chains along [001]. The chains are linked by C-H?pi inter-actions, forming a
      three-dimensional structure. 

PMID- 24940279
TI  - 3-Bromo-methyl-4-meth-oxy-2-(2-nitro-phen-yl)-9-phenyl-sulfonyl-9H-carbazole.
AB  - In the title compound, C26H19BrN2O5S, the carbazole tricycle is essentially
      planar, with the largest deviation being 0.126 (3) A for the C atom connected to
      the nitro-phenyl group. The carbazole moiety is almost orthogonal to the benzene
      rings of the adjacent phenyl-sulfonyl and nitro-phenyl groups, making dihedral
      angles of 85.43 (15) and 88.62 (12) degrees , respectively. The mol-ecular
      conformation is stabilized by two C-H?O hydrogen bonds involving the sulfone
      group, which form similar six-membered rings. In the crystal, mol-ecules
      symmetrically related by a glide plane are linked in C(6) chains parallel to
      [001] by C-H?O hydrogen bonds formed with the participation of the nitro group.
      The chains are reinforced by additional C-H?pi inter-actions. 

PMID- 24940280
TI  - Methyl (E)-3-(2-formyl-phen-oxy)acrylate.
AB  - In the title compound, C11H10O4, the methyl acrylate sub-stituent adopts an
      extended E conformation with all torsion angles close to 180 degrees . The
      conformation of the keto group with respect to the olefinic double bond is
      typically S-trans. In the crystal, mol-ecules are linked via pairs of C-H?O
      hydrogen bonds, forming inversion dimers with an R 2 (2)(8) graph-set motif. The
      dimers are further linked via C-H?O hydrogen bonds, forming chains along [001],
      which enclose R 3 (2)(16) graph-set ring motifs. The keto group O atomaccepts two
      C-H?O interactions. 

PMID- 24940281
TI  - 7,7-Dimethyl-2-methyl-amino-4-(4-methyl-phenyl)-3-nitro-7,8-di-hydro-4H-chromen
      5(6H)-one.
AB  - In the title compound, C19H22N2O4, the six-membered cyclo-hexenone ring of the
      chromene unit adopts an envelope conformation, with the dimethyl-substituted C
      atom as the flap, while the pyran ring has a boat conformation. These two mean
      planes are inclined to one another by 6.65 (13) degrees .The benzene ring is
      normal to the 4H-chromene moiety mean plane, making a dihedral angle of 89.18 (5)
      degrees . The methyl-amine and nitro groups are slightly twisted from the
      chromene moiety mean plane, with torsion angles C-N-C-O = 1.70 (18) and O-N-C-C =
      0.15 (18) degrees . The mol-ecular structure is characterized by an intra
      molecular N-H?O hydrogen bond, which generates an S(6) ring motif. In the
      crystal, mol-ecules are linked via pairs of weak C-H?O hydrogen bonds, forming
      inversion dimers. These dimers are connected by further C-H?O hydrogen bonds,
      forming sheets lying parallel to (10-1). 

PMID- 24940282
TI  - 5-Cyano-1,3-phenyl-ene di-acetate.
AB  - In the title mol-ecule, C11H9NO4, the two acet-oxy groups are twisted from the
      plane of the benzene ring by 67.89 (4) and 53.30 (5) degrees . Both carbonyl
      groups are on the same side of the aromatic ring. In the crystal, weak C-H?O
      hydrogen bonds link mol-ecules into layers parallel to the ac plane. The crystal
      packing exhibits pi-pi inter-actions between the aromatic rings, indicated by a
      short inter-centroid distance of 3.767 (3) A. 

PMID- 24940283
TI  - (E)-1,3-Dimethyl-2,6-di-phenyl-piperidin-4-one O-(phen-oxy-carbon-yl)oxime.
AB  - The title piperidine derivative, C26H26N2O3, has an E conformation about the N=C
      bond. The piperidine ring has a chair conformation and its mean plane is almost
      perpendicular to the attached phenyl rings, making dihedral angles of 87.47 (9)
      and 87.34 (8) degrees . The planes of these two phenyl rings are inclined to one
      another by 60.38 (9) degrees . The plane of the terminal phenyl ring is tilted at
      an angle of 32.79 (9) degrees  to the mean plane of the piperidine ring. The mol
      ecular conformation is stabilized by two intra-molecular C-H?O contacts. There
      are no significant inter-molecular inter-actions in the crystal. 

PMID- 24940284
TI  - 3-(2-Methyl-1,3-benzo-thia-zol-3-ium-3-yl)propane-1-sulfonate monohydrate.
AB  - In the title hydrated zwitterion, C11H13NO3S2.H2O, the N-C-C-C and C-C-C-S
      torsion angles in the side-chain are 171.06 (14) and 173.73 (12) degrees ,
      respectively. In the crystal, inversion-related mol-ecules are pi-stacked with an
      inter-planar separation of 3.3847 (2) A. O-H?O hydrogen bonds link inversion
      related mol-ecules with a pair of water mol-ecules to form R 4 (2)(8) rings. The
      closest S?S contact is 3.4051 (15) A between inversion-related mol-ecules. 

PMID- 24940285
TI  - 2,5-Di-bromo-3,6-dimeth-oxycyclo-hexa-2,5-diene-1,4-dione.
AB  - In the structure of the title compound, C8H6Br2O4, the complete mol-ecule is
      generated by the application of a centre of inversion. The mol-ecule is planar
      (r.m.s. deviation for all non-H atoms but methyl C = 0.0358 A), with only the
      methyl groups being deviated from the plane [by +/-0.321 (4) A]. In the crystal
      packing, Br?O(methoxy) halogen bonds [3.2407 (19) A] connect molecules into
      supramolecular layers parallel to (101). 

PMID- 24940286
TI  - 2-(2-Methyl-phen-yl)-N-(1,3-thia-zol-2-yl)acetamide.
AB  - In the title compound, C12H12N2OS, the dihedral angle between the benzene and
      thia-zole rings is 83.5 (7) degrees . The acetamide group is almost coplanar with
      the thia-zole ring, being twisted from it by 4.2 (9) degrees . In the crystal,
      pairs of N-H?N hydrogen bonds link mol-ecules into inversion dimers, generating R
      2 (2)[8] loops; the dimers are stacked along [001]. 

PMID- 24940288
TI  - Ethyl 8-meth-oxy-4-oxo-1,4-di-hydro-quinoline-3-carboxyl-ate.
AB  - In the title compound, C13H13NO4, the asymmetric unit contains four independent
      mol-ecules, each exhibiting an intra-molecular N-H?O hydrogen bond. The ethyl
      group in one of the four mol-ecules is disordered, with a refined occupancy ratio
      of 0.295 (16):0.705 (16). A face-to-face stacking inter-action is found between
      the benzene rings of the quinoline units of two of the mol-ecules [centroid
      centroid distance = 3.541 (2) A], which are sandwiched by the other two mol
      ecules through N-H?O hydrogen bonding. In the crystal, the sandwiched mol-ecules
      are assembled via stacking inter-actions along the b-axis direction with their
      translation-symmetry equivalents [centroid-centroid distance = 3.529 (2) A], and
      are further linked through N-H?O hydrogen bonding. The other two mol-ecules are
      linked via stacking inter-actions with their inversion-symmetry equivalents
      [centroid-centroid distances = 3.512 (3) and 3.716 (4) A] and via N-H?O hydrogen
      bonding. 

PMID- 24940287
TI  - 4-Acetyl-piperazinium picrate.
AB  - In the title salt, C6H13N2O(+).C6H2N3O7 (-) (systematic name: 4-acetyl-piperazin
      1-ium 2,4,6-tri-nitro-phenolate), the piperazin-1-ium ring has a slightly
      distorted chair conformation. In the picrate anion, the mean planes of the two o
      NO2 and p-NO2 groups are twisted with respect to the benzene ring by 15.0 (2),
      68.9 (4) and 4.4 (3) degrees , respectively. In the crystal, N-H?O hydrogen bonds
      are observed, linking the ions into an infinite chain along [010]. In addition,
      weak cation-anion C-H?O inter-molecular inter-actions and a weak pi-pi stacking
      inter-action between the benzene rings of the anions, with an inter-centroid
      distance of 3.771 (8) A, help to stabilize the crystal packing, giving an overall
      sheet structure lying parallel to (100). Disorder was modelled for one of the O
      atoms in one of the o-NO2 groups over two sites with an occupancy ratio of 0.57
      (6):0.43 (6). 

PMID- 24940289
TI  - 3-Methyl-sulfanyl-5-phenyl-1,2,4-triazine.
AB  - In the mol-ecule of the title compound, C10H9N3S, the dihedral angle between the
      triazine and phenyl rings is 11.77 (7) degrees . In the crystal, mol-ecules are
      linked by pi-pi stacking inter-actions [centroid-centroid distances = 3.7359 (3)
      and 3.7944 (4) A], forming layers parallel to the bc plane. 

PMID- 24940290
TI  - (3Z)-3-[(Z)-2-(2-Oxoindolin-3-yl-idene)hydrazin-1-yl-idene]indolin-2-one 0.17
      hydrate.
AB  - In the title compound, C16H10N4O2.0.17H2O, prepared by the one-step condensation
      reaction of isatin with hydrazine hydrate under microwave irradiation, the
      complete organic mol-ecule is generated by crystallographic inversion symmetry
      and therefore exists in an S-trans conformation. In the crystal, mol-ecules are
      linked by N-H?O hydrogen bonds, generating a three-dimensional framework with
      [001] channels, which are occupied by the disordered water mol-ecules. 

PMID- 24940291
TI  - (2E,7E)-2,7-Bis[(thio-phen-2-yl)methyl-idene]cyclo-hepta-none.
AB  - The whole molecule of the title compound, C17H16OS2, is generated by two-fold
      rotational symmetry. The carbonyl C and O atoms of the cycloheptanone ring lie on
      the twofold rotation axis which bisects the opposite -CH2-CH2- bond of the ring.
      The mol-ecule exists in an E,E conformation with respect to the C=C double bond.
      The cyclo-hepta-none ring exhibits a twisted chair conformation and its mean
      plane makes a dihedral angle of 50.12 (19) degrees  with the planes of the thio
      phene rings. The two S atoms are in an anti arrangement with respect the carbonyl
      O atom and the dihedral angle between the two thio-phene ring planes is 69.38 (7)
      degrees . In the molecule, there are two intramolecular C-H?S hydrogen bond,
      forming S(6) ring motifs. In the crystal, inversion dimers are generated via
      pairs of C-H?O hydrogen bonds. These dimers are inter-connected by another inter
      action of the same kind with a neighbouring mol-ecule, forming a mol-ecular chain
      along the c-axis direction. 

PMID- 24940292
TI  - Diethyl (E)-2,3-bis-[(E)-(2-methyl-2-phenyl-hydrazin-1-yl-idene)meth-yl]but-2
      enedioate.
AB  - The complete mol-ecule of the title compound, C24H28N4O4, is generated by
      crystallographic inversion symmetry. The ethyl side chain is disordered over two
      sets of sites in a 0.57 (4):0.43 (4) ratio. The dihedral angles between the
      methyl-idene group and the phenyl ring and ester side chain (major conformation)
      are 7.61 (8) and 86.95 (8) degrees , respectively. In the crystal, mol-ecules are
      linked via C-H?O hydrogen bonds, forming corrugated sheets lying parallel to
      (010). 

PMID- 24940293
TI  - 5-[(2-Hy-droxy-eth-yl)(meth-yl)amino]-thio-phene-2-carbaldehyde.
AB  - In the title compound, C8H11NO2S, the aldehyde group is approximately coplanar
      with the thio-phene ring [maximum deviation = 0.023 (2) A]. In the crystal, mol
      ecules are linked by O-H?O hydrogen bonds into supra-molecular chains propagating
      along the a-axis direction. 

PMID- 24940294
TI  - trans-2,5-Di-methyl-piperazine-1,4-diium dinitrate.
AB  - In the structure of the title salt, C6H16N2 (2+).2NO3 (-), the cations are
      connected to the anions through bifurcated N-H?(O,O) and weak C-H?O hydrogen
      bonds, generating corrugated layers parallel to the (100) plane. The organic
      cation is centrosymmetric and the diprotonated piperazine ring adopts a chair
      conformation, with the methyl groups occupying equatorial positions. 

PMID- 24940295
TI  - 4-{[4-(Di-methyl-amino)-benzyl-idene]amino}-benzene-sulfonamide.
AB  - The title Schiff base compound, C15H17N3O2S, is non-planar with a dihedral angle
      of 69.88 (4) degrees  between the planes of the benzene rings. In the crystal,
      pairs of N-H?N hydrogen bonds, between the sulfonamide nitro-gen-H atom and the
      azomethine N atom, link the mol-ecules into inversion dimers, forming R 2 (2)(16)
      ring motifs. These dimers are linked by N-H?O hydrogen bonds, between the
      sulfonamide nitro-gen-H atom and one sulfonamide O atom, forming sheets lying
      parallel to (100). Within the sheets there are weak parallel slipped pi-pi inter
      actions involving inversion-related benzene-sulfonamide rings [centroid-centroid
      distance = 3.8800 (9) A; normal distance = 3.4796 (6) A; slippage = 1.717 A]. 

PMID- 24940296
TI  - Methyl 2-[(3RS,4RS)-3-phenyl-4-(phenyl-sulfon-yl)isoxazolidin-2-yl]acetate.
AB  - In the title compound, C18H19NO5S, the five-membered isoxazolidine ring is in a
      half-chair conformation, and the phenyl rings are oriented at a dihedral angle of
      66.53 (3) degrees . In the crystal, C-H?O hydrogen bonds link the mol-ecules into
      a three-dimensional supra-molecular structure. A weak C-H?pi inter-action is also
      observed between adjacent mol-ecules. 

PMID- 24940297
TI  - N'-[(4Z)-1-(3-Methyl-5-oxo-1-phenyl-4,5-di-hydro-1H-pyrazol-4-yl-idene)hex
      yl]benzene-sulfono-hydrazide.
AB  - In the title compound, C22H26N4O3S, the dihedral angle between the pyrazoloneand
      phenyl rings is 21.73 (4) degrees . The benzensulfono-hydrazide group adopts a
      gauche conformation about the N-N vector. The C-N-N-S torsion angle is -109.88
      (13) degrees . The mol-ecule exists as the enamine tautomeric form (C=C-NH). An
      intra-molecular N-H?O=C hydrogen bond occurs. In the crystal, mol-ecules are
      linked by pairs of N-H?O=C hydrogen bonds, forming centrosymmetric dimers. 

PMID- 24940298
TI  - N-Ethyl-2-[1-(2-hy-droxy-naphthalen-1-yl)ethyl-idene]hydrazinecarbo-thio-amide.
AB  - In the title compound, C15H17N3OS, the dihedral angle between the mean planes of
      the 2-hy-droxy-napthyl ring system and the hydrazinecarbo-thio-amide group is
      73.7 (3) degrees . In the crystal, weak O-H?S and C-H?O inter-actions and pi-pi
      stacking inter-actions involving one of the hy-droxy-napthyl rings with a
      centroid-centroid distance of 3.6648 (14) A are observed, forming infinite chains
      along [010]. In addition, N-H?S inter-actions occur. 

PMID- 24940299
TI  - 4-[(E)-(4-Hy-droxy-benzyl-idene)amino]-3-methyl-1H-1,2,4-triazole-5(4H)-thione.
AB  - The title compound, C10H10N4OS, is nearly planar with the mean planes of the hy
      droxy-benzyl and triazole rings inclined at an angle of only 3.2 (7) degrees . In
      the crystal, O-H?N hydrogen bonds between the hy-droxy group and the triazole
      ring in concert with weak N-H?S inter-molecular inter-actions between the
      triazole ring and thione group form chains along [-210] enclosing R 2 (2)(8)
      graph-set motifs. A weak intra-molecular C-H?S inter-action and inter-molecular
      pi-pi inter-actions [centroid-centroid distance = 3.5990 (15) A] are also
      observed. 

PMID- 24940300
TI  - N-Ethyl-2-[1-(2-hy-droxy-4-methyl-phen-yl)ethyl-idene]hydrazinecarbo-thio-amide.
AB  - The title compound, C12H17N3OS, crystallizes with two independent mol-ecules (A
      and B) in the asymmetric unit. The dihedral angle between the mean planes of the
      benzene ring and the hydrazinecarbo-thio-amide group are 6.9 (4) and 37.2 (5)
      degrees  in mol-ecules A and B, respectively. An intra-molecular O-H?N hydrogen
      bond is observed in each mol-ecule. This serves to maintain an approximately
      planar conformation for mol-ecule A, but leaves a significant twist between these
      two groups in mol-ecule B. In the crystal, a weak N-H?S inter-action is observed,
      forming inversion dimers among the B mol-ecules and resulting in an R 2 (2)(8)
      motif. These dimers are further inter-connected by weak N-H?O and C-H?O inter
      molecular inter-actions, forming chains along [011]. 

PMID- 24940301
TI  - 3-(4-Fluoro-benzo-yl)-4-(4-fluoro-phen-yl)-4-hy-droxy-2,6-di-phenyl-cyclo-hexane
      1,1-dicarbo-nitrile.
AB  - In the title compound, C33H24F2N2O2, the cyclo-hexane ring adopts a slightly
      distorted chair conformation. The dihedral angle between the planes of the phenyl
      rings is 71.80 (9) degrees , while the planes of the fluoro-phenyl and fluoro
      benzoyl rings are inclined to one another by 31.04 (10) degrees . The dihedral
      angles between the planes of the phenyl ring adjacent to the 4-hydroxy group and
      those of the the fluoro-phenyl and fluoro-benzoyl rings are 51.64 (10) and 34.31
      (10) degrees , respectively, while the corresponding angles for the phenyl ring
      adjacent to the 3-(4-fluorobenzoyl) group are 57.51 (9) and 85.02 (10) degrees ,
      respectively. An intra-molecular O-H?O hydrogen bond generates an S(6) ring
      motif. In the crystal, mol-ecules are linked via pairs of O-H?N hydrogen bonds,
      forming inversion dimers. The dimers are linked via C-H?N and C-H?O hydrogen
      bonds, forming chains along the c-axis direction. C-H?F hydrogen bonds link the
      chains into sheets lying parallel to the bc plane. 

PMID- 24940302
TI  - {2-[(4-Nitro-benzyl-idene)amino]-4,5,6,7-tetrahydro-1-benzo-thio-phen-3-yl}(phen
      yl)methanone.
AB  - In the title compound, C22H18N2O3S, disorder is found in the benzoyl group (A and
      B), as well as for four C atoms of the cyclo-hexene ring. Two orientations were
      modeled in a 0.583 (5):0.417 (5) ratio. The cyclo-hexene ring is in a distorted
      chair conformation. The dihedral angles between the mean plane of the thio-phene
      ring and the 4-nitro-benzene and phenyl rings are 30.9 (8) and 64.8 (3) (A) and
      62.4 (7) degrees  (B). The mean planes of the 4-nitro-benzene and the phenyl
      rings are almost perpendicular to each other, with dihedral angles of 85.4 (1)
      (A) and 83.9 (8) degrees  (B). An extensive array of weak C-H?O inter-actions
      consolidate mol-ecules into a three-dimensional architecture, forming chains
      along [001] and [010] and layers parallel to (011). 

PMID- 24940303
TI  - 4'-Phenyl-3,4-di-hydro-2H-spiro-[naph-tha-lene-1,3'-[1,2,4]triazole]-5'-thione.
AB  - In the title mol-ecule, C17H15N3S, the phenyl group makes a dihedral angle of
      57.29 (11) degrees  with the mean plane of the triazole ring, which in turn makes
      an angle of 86.83 (12) degrees  with the plane of the aromatic portion of the
      tetra-hydro-naphthalene moiety. In the crystal, mol-ecules are linked by weak C
      H?S hydrogen bonds into supra-molecular chains propagating along the a-axis
      direction. Weak C-H?pi inter-actions are also observed. 

PMID- 24940304
TI  - Snake venom L-amino acid oxidases: an overview on their antitumor effects.
AB  - The L-amino acid oxidases (LAAOs) constitute a major component of snake venoms
      and have been widely studied due to their widespread presence and various
      effects, such as apoptosis induction, cytotoxicity, induction and/or inhibition
      of platelet aggregation, hemorrhage, hemolysis, edema, as well as antimicrobial,
      antiparasitic and anti-HIV activities. The isolated and characterized snake venom
      LAAOs have become important research targets due to their potential
      biotechnological applications in pursuit for new drugs of interest in the
      scientific and medical fields. The current study discusses the antitumor effects
      of snake venom LAAOs described in the literature to date, highlighting the
      mechanisms of apoptosis induction proposed for this class of proteins. 

PMID- 24940305
TI  - Impact of moderate versus mild aerobic exercise training on inflammatory
      cytokines in obese type 2 diabetic patients: a randomized clinical trial.
AB  - BACKGROUND: Recently some plasma biomarkers of inflammation have been recognized
      as important cardiovascular risk factors. There is little information about the
      effects of aerobic exercise training on these biomarkers and the risk of
      metabolic complications in obese type 2 diabetes patients. OBJECTIVE: To compare
      the impact of moderate versus mild aerobic exercise training on the inflammatory
      cytokines in obese type 2 diabetic patients. METHODS: Fifty obese type 2 diabetic
      patients of both sexes with body mass index (BMI) varying from 31 to 36 kg/m(2),
      non smokers, free from respiratory, kidney, liver, metabolic and neurological
      disorders, participated in this study. Their age ranged from 40 to 55 years. The
      subjects were included into two equal groups; the first group (A) received
      moderate aerobic exercise training. The second group (B) received mild aerobic
      exercise training, three times / week for 3 months. RESULTS: The mean values of
      leptin, TNF- alpha, IL2, IL4, IL6, HOMA-IR and HBA1c were significantly decreased
      in group (A) and group (B). Also, there were significant differences between both
      groups after treatment. CONCLUSION: Moderate aerobic exercise training modulates
      inflammatory cytokines more than mild aerobic exercise training in obese type 2
      diabetic patients.

PMID- 24940306
TI  - Erratum: Differential expressed genes in ECV304 Endothelial-like Cells infected
      with Human Cytomegalovirus.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is a virus which has the potential to
      alter cellular gene expression through multiple mechanisms. OBJECTIVE: With the
      application of DNA microarrays, we could monitor the effects of pathogens on host
      cell gene expression programmes in great depth and on a broad scale. METHODS:
      Changes in mRNA expression levels of human endothelial-like ECV304 cells
      following infection with human cytomegalovirus AD169 strain was analyzed by a
      microarray system comprising 21073 60-mer oligonucleotide probes which represent
      18716 human genes or transcripts. RESULTS: The results from cDNA microarray
      showed that there were 559 differential expressed genes consisted of 471
      upregulated genes and 88 down-regulated genes. Real-time qPCR was performed to
      validate the expression of 6 selected genes (RPS24, MGC8721, SLC27A3, MST4, TRAF2
      and LRRC28), and the results of which were consistent with those from the
      microarray. Among 237 biology processes, 39 biology processes were found to be
      related significantly to HCMV-infection. The signal transduction is the most
      significant biological process with the lowest p value (p=0.005) among all
      biological process which involved in response to HCMV infection. CONCLUSION:
      Several of these gene products might play key roles in virus-induced
      pathogenesis. These findings may help to elucidate the pathogenic mechanisms of
      HCMV caused diseases. [This corrects the article on p. 243 in vol. 13, PMID:
      24235919.].

PMID- 24940307
TI  - Compliance with iron-folic acid (IFA) therapy among pregnant women in an urban
      area of south India.
AB  - BACKGROUND: Anaemia is highly prevalent among pregnant women and iron deficiency
      is the most important cause. Like many other countries, India has policies to
      give pregnant women iron supplements. Non-compliance is one important challenging
      factor in combating anaemia. OBJECTIVE: To estimate the compliance for IFA
      tablets among pregnant women and to study the social factors influencing it.
      METHODOLOGY: This study included 190 pregnant women seeking ante-natal care in
      tertiary health centres in the Mangalore city in south India. After Institutional
      Ethics Committee (IEC) approval, data was collected by personal interview.
      Missing >2 doses consecutively was considered non-compliance. The data was
      analyzed using SPSS (Statistical Package for Social Sciences) version 11.5.
      RESULTS: The mean age of the study population was 25.8 years (SD: 4.1). Most of
      the subjects consumed mixed diet and 72.1% belonged to lower socioeconomic
      status. Overall, compliance with IFA tablets was 64.7%. Compliance increased with
      the increase in age, birth order and single daily dose. Forgetfulness and both
      perceived as well as experienced side effects of IFA therapy were the important
      factors for non-compliance. CONCLUSION: There was a moderate level of compliance
      towards IFA tablets with key social and demographic factors playing an important
      role.

PMID- 24940308
TI  - Clinical and audiometric features of presbycusis in Nigerians.
AB  - BACKGROUND: Presbycusis is the most common sensory impairment associated with
      ageing and it presents with variability of symptoms. Physicians need to recognize
      early clinical and audiometric signs of presbycusis in order to render adequate
      and quality care to patients and reduce associated morbidities. OBJECTIVE: To
      characterize the clinical modes of presentation and the typical audiometric
      tracings among patients with presbycusis. METHODS: This descriptive, prospective
      hospital-based study was conducted in the Ear, Nose and Throat (ENT) clinic of
      Olabisi Ona hing Hospital, (OOUTH) Sagamu, Nigeria. Patients with clinical
      diagnosis of presbycusis confirmed with bilateral sensorineural hearing loss
      (SNHL) on diagnostic audiometry were administered with questionnaires.
      Information obtained was analyzed using SPSS statistical package version 17.0 and
      presented in descriptive forms as percentages, means and graphs. RESULTS: Sixty
      nine patients were diagnosed with presbycusis (M:F =1.6:1). Modal age group was
      71-80 years. Hearing loss 88.4%, tinnitus 79.7% and vertigo 33.3% were the major
      symptoms on presentation. The average duration of symptoms before presentation
      was 2.6 years. There was positive history of ototoxic drugs usage in 24.6 %,
      family history in 11.6 %, hypertension in 34.8% and osteoarthritis in 13.0%. The
      most common type of audiometric pattern was strial. Hearing losses increased with
      age both at the speech and at the higher frequencies of sounds. CONCLUSIONS: We
      found hearing impairment affected both speech and higher frequencies and the
      strial type of audiometric pattern was most common. The need for screening for
      hearing impairment from early middle age in symptomatic individuals is
      emphasized.

PMID- 24940309
TI  - Care of terminally-ill patients: an opinion survey among critical care healthcare
      providers in the Middle East.
AB  - BACKGROUND: Modern medicine has allowed physicians to support the dying
      terminally-ill patient with artificial means. However, a common dilemma faced by
      physicians in general, and intensivist in particular is when to limit or withdraw
      aggressive intervention. OBJECTIVE: To study the effect of training background
      and seniority on Do-not to resuscitate (DNR) decisions in the Middle East.
      METHODS: Anonymous questionnaire sent to members of the Pan Arab Society of
      Critical Care. RESULTS: The response rate was 46.2%. Most of the responders were
      Muslim (86%) and consultants (70.9%). Majority of the responders were trained in
      western countries. Religion played a major role in 59.3% for making the DNR
      decision. DNR was considered equivalent to comfort care by 39.5%. In a futile
      case scenario, Do Not Escalate Therapy was preferred (54.7%). The likelihood of a
      patient, once labeled DNR, being clinically neglected was a concern among 46.5%.
      Admission of DNR patients to the ICU was acceptable for 47.7%. Almost one-half of
      the responders (46.5%) wanted physicians to have the ultimate authority in the
      DNR decision. Training background was a significant factor affecting the
      interpretation of the term no code DNR (P< 0.008). CONCLUSION: Training
      background and level of seniority in critical care provider does not impact
      opinion on most of end of life issues related to care of terminally-ill patients.
      However, DNR is considered equivalent to comfort care among majority of Middle
      Eastern trained physicians.

PMID- 24940310
TI  - Prevalence of noise induced hearing loss among employees at a mining industry in
      Zimbabwe.
AB  - BACKGROUND: Noise induced hearing loss (NIHL) is within the top five occupational
      illnesses in Zimbabwe. Workers at a mining company complained about loss of
      hearing at the mine clinic. OBJECTIVE: To determine the prevalence of NIHL among
      employees at the Mine. METHODS: We conducted a descriptive cross sectional study
      at the mine. Workers were proportionally selected to represent all the mine
      departments or working areas. We measured noise levels at various mine sites,
      conducted a walk-through survey to observe noise related worker practices and
      conducted audiometric testing. RESULTS: Mean age for workers was 34.8+/-7.6 years
      and the mean duration of exposure to noise was 7.5+/-1.2 years. All workers could
      define noise. Ninety (53%) workers attributed NIHL to noisy work environment.
      Excessive noise levels were in Plant Processing (94 dBA), Underground Mining (102
      dBA) and (Underground Workshop (103 dBA). Sixty two (36.7%) workers had NIHL.
      NIHL increased as a function of age (chi square=30.99 df=3 p<0.01) and was
      associated with work area (chi square=24.96 df=5 p<0.01). Observed workers took
      heed of noise warnings. There was no documented hearing conservation program at
      the mine. CONCLUSION: The prevalence of NIHL of 37% is high. Age and work area
      were associated with NIHL. Studies reported that age tends to distort the
      relationship between noise exposure and NIHL. Mine management should institute a
      hearing conservation program to protect employees against hazardous noise.
      Management may meanwhile use administrative controls and adhere to permissible
      exposure limits according to the noise regulations.

PMID- 24940311
TI  - A review of the management of perforated duodenal ulcers at a tertiary hospital
      in south western Nigeria.
AB  - BACKGROUND: Gastro-duodenal perforations are common and may complicate peptic
      ulcer disease. Management is often by surgical closure. OBJECTIVE: To determine
      the patterns of presentation and mode of management of duodenal ulcer
      perforations. METHODS: Retrospective review of patients with duodenal ulcer
      perforations seen at the Obafemi Awolowo University Teaching Hospital between
      June 2001 and July 2011. Patients' records were reviewed for demography, duration
      of disease, probable risk factors, type of surgery and complications. Data
      obtained was analyzed using SPSS 15.0. RESULT: Forty- five patients were
      reviewed. There were 37 males (82.2%). Mean age was 39.7years (range 15-78years).
      There were 10 (22.6%) students and 8(17.8%) farmers. NSAIDs abuse (11), previous
      peptic ulcer disease (2), and no prior dyspeptic symptoms (20) constituted 24.4%,
      4.4% and 44.4% respectively of cases. Seven (16%) patients presented less than 24
      hours of onset of illness. Forty one perforations (91.1%) involved the first part
      of duodenum. Twenty two (49%) patients had Graham's omental patch. We had one
      (2.2%) failed repair and six (13.3%) mortalities. CONCLUSION: Late presentation
      of duodenal ulcer perforation is common with high mortality. Pragmatic surgical
      intervention with Graham's omentopexy with broad spectrum antibiotics is still
      commonly practiced.

PMID- 24940312
TI  - Counselling at primary health facilities and level of knowledge of antenatal
      attendees and their attitude on prevention of Mother to Child Transmission of HIV
      in Dar-es salaam, Tanzania.
AB  - BACKGROUND: Children living with HIV worldwide majority are infected through
      mother to child transmission of HIV (MTCT) acquired during pregnancy. Knowledge,
      attitude and behavioral changes are pivot tools towards success of any
      interventions. OBJECTIVES: To determine the effectiveness of counseling on HIV
      done in primary health facilities (PHF), level of knowledge gained and attitude
      changes towards PMTCT. METHODS: A cross sectional study assessing pregnant
      women's knowledge and their attitude towards PMTCT was conducted in Temeke
      district from October 2010 to Jan 2011 using a structured questionnaire. RESULTS:
      A total of 383 antenatal attendees were referred to Temeke district for
      management after counselled and tested for HIV in PHFs. Majority (86.9%) had
      primary education and good knowledge on MTCT. Correct timing of ARVs prophylaxis
      (15.7%) as preventive measures for MTCT was poor. Education and employment were
      associated with good knowledge on MTCT of HIV. Women had positive attitudes
      towards HIV counseling and testing, but stigma was a barrier to disclosure of
      one's serostatus. CONCLUSION: There is knowledge gap in routine PMTCT counseling
      among antenatal attendees in our PHFs. Effective counseling on PMTCT in the PHFs
      will bridge the identified knowledge gap and help in reduction of pediatric HIV.

PMID- 24940313
TI  - Roles of family dynamics on adherence to highly active antiretroviral therapy
      among people living with HIV/AIDS at a tertiary hospital in Osogbo, south-west
      Nigeria.
AB  - BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) has been
      proven to be the only effective treatment for HIV/AIDS worldwide. Good adherence
      to HAART might require good family support. OBJECTIVE: To determine the family
      dynamics and social support of people living with HIV/AIDS (PLWHA) and its roles
      on HAART adherence at an ARV treatment clinic in Osogbo, Nigeria. METHOD:
      Descriptive cross-sectional study. Consenting PLWHA on HAART were interviewed
      using pre-tested semistructured questionnaire incorporating Perceived Social
      Support- Family Scale and Family APGAR. HAART adherence was measured using
      patient self report. RESULTS: A total of 379 PLWHA were interviewed. Their mean
      age was 40.8 (SD=9.9) years. Most (60.7%) were females. More than half (55.7%)
      were currently married and the majority (72.1%) had secondary education and were
      Yoruba (86.3%). Most respondents (95.5%) were adherent to HAART. Over 90% were
      satisfied with support received from their family while 82.3% were treated like
      other family members. Most attributed their HAART adherence to the care and
      support received from their family. CONCLUSION: Most PLWHA had good social
      support and were adherent to HAART.

PMID- 24940315
TI  - In vivo hypoglycemic effect of methanolic fruit extract of Momordica charantia L.
AB  - BACKGROUND: Momordica charantia L. is a medicinal plant commonly used in the
      management of diabetes mellitus. OBJECTIVES: We investigated the blood glucose
      lowering effect of the methanolic fruit extract of the Ugandan variety of M.
      charantia L. in alloxan-induced diabetic albino rats. METHODS: 500g of M.
      charantia powder were macerated in methanol and the extract administered to two
      groups of alloxan-induced diabetic rats. The first group received 125mg/kg, the
      second 375mg/kg and a third group 7mg/kg of metformin. A fourth group received
      1ml normal saline. Fasting blood glucose (FBG) levels were measured at
      0.5,1,2,3,5,8 and 12 hours and compared using one-way ANOVA. RESULTS: There was
      an initial rise in FBG for 1 hour after administration of extracts followed by
      steep reductions. Significant reduction in FBG occurred at 2 hours for 125mg/kg
      of extract (-3.2%, 313+/-25.9 to 303+/-25.0mg/dL, p = 0.049), 375mg/kg of extract
      (-3.9%, 356+/-19.7 to 342+/-20.3mg/dL, p = 0.001), and metformin (-2.6%, 344+/
      21.7 to 335+/-21.1mg/dL, p = 0.003) when compared to normal saline. The maximum
      percentage reduction in FBG by both extracts occurred between 3 and 12 hours post
      dose. CONCLUSIONS: The methanolic fruit extract of M. charantia exhibits dose
      dependent hypoglycaemic activity in vivo.

PMID- 24940314
TI  - Decompensated cirrhosis-related admissions in a large urban hospital in Uganda:
      prevalence, clinical and laboratory features and implications for planning
      patient management.
AB  - BACKGROUND: Cirrhosis-related complications are a major cause of morbidity and
      mortality in areas where its risk factors are endemic. OBJECTIVE: We determined
      the prevalence of decompensated cirrhosis among patients on the gastroenterology
      service of Mulago Hospital and described the clinical and laboratory features of
      these patients. METHODS: All patients admitted to the unit were assessed and
      their diagnosis documented. Patients with cirrhosis had clinical features of
      decompensation recorded. History of alcohol consumption was taken and testing for
      hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV)
      performed. RESULTS: Between September 2010 and January 2011, we enrolled 482
      patients. The majority (53.7%) were male, overall median age 38 years.
      Decompensated cirrhosis was diagnosed in 85 (17.6%) patients. Of the 85 patients,
      47 (55.3%) gave a history of alcohol intake, HBsAg was positive in 23 (27.1%) and
      anti-HCV in 3 (3.5%). Decompensation was defined by ascites among 81 (95.3%)
      patients, variceal bleeding in 31 (36.5%), encephalopathy in 20 (23.5%).
      CONCLUSION: Cirrhosis is common in Mulago hospital presenting mainly with ascites
      and variceal bleeding. Aside from controlling causes of liver diseases,
      especially alcohol and hepatitis B virus infection, in the interim it is
      necessary to manage complications in patients who already have cirrhosis.

PMID- 24940317
TI  - The response effect of pheochromocytoma (PC12) cell lines to oxidized multi
      walled carbon nanotubes (o-MWCMTs).
AB  - BACKGROUND: The applications of oxidized carbon nanotubes (o-CNTs) have shown
      potentials in novel drug delivery including the brain which is usually a
      challenge. This underscores the importance to study its potential toxic effect in
      animals. Despite being a promising tool for biomedical applications little is
      known about the safety of drugs in treating brain diseases. The toxicity of
      oxidized multi-walled carbon nanotubes (o-MWCNTs) are of utmost concern and in
      most in-vitro studies conducted so far are on dendritic cell (DC) lines with
      limited data on PC12 cell lines. OBJECTIVES: We focused on the effect of o-MWCNTs
      in PC12 cells in vitro: a common model cell for neurotoxicity. METHODS: The
      pristine multi-walled carbon nanotubes (p-MWCNTs) were produced by the swirled
      floating catalytic chemical vapour deposition method (SFCCVD). The p-MWCNTs were
      then oxidized using purified H2SO4/HNO3 (3:1v/v) and 30% HNO3 acids to produce o
      MWCNTs. The Brunauer-Emmett-Teller (BET), transmission electron microscopy (TEM),
      Scanning electron microscopy (SEM), thermogravimetric analyser (TGA) and Raman
      spectroscopy techniques were used to characterize the MWCNTs. The PC12 cells were
      cultured in RPMI medium containing concentrations of o-MWCNTs ranging from 50 to
      200 ug/ml. RESULTS: The o-MWCNTs demonstrated slight cytotoxicity at short time
      period to PC12 neuronal cells whilst at longer time period, no significant (p >
      0.05) toxicity was observed due to cell recovery. CONCLUSION: In conclusion, the
      o-MWCNTs did not affect the growth rate and viability of the PC12 cells due to
      lack of considerable toxicity in the cells during the observed time period but
      further investigations are required to determine cell recovery mechanism.

PMID- 24940316
TI  - The effects of maternal haemoglobin as an indicator of maternal nutritional
      status on, maternal measles antibodies of mother-infant pairs at birth.
AB  - BACKGROUND: Maternal measles antibodies (MMA) are actively transferred through
      the placenta from mother to foetus. A relationship could exist between MMA of
      mother-infant pairs and maternal nutritional indicator (haemoglobin). OBJECTIVES:
      This study reviewed the effects of maternal haemoglobin (Hb) on MMA of mother
      infant pairs at birth. METHODS: One hundred and fifty three mother-infant pairs
      were enrolled in this study using the systematic random sampling method. Means of
      maternal Hb and MMA of mother-infant pairs were compared using the Student t
      test. Correlation coefficients of maternal Hb and MMA of mother-infant pairs were
      also determined. Multivariate analysis of variable (MANOVA) and covariates
      (MANCOVA) was used to investigate the effects of maternal Hb (fixed factor),
      gestational age, maternal age, birth weight (covariates) on combined MMA of
      mother-infant pairs (dependent factors). Benferroni adjusted Univariate linear
      regression was used to investigate the dependent variables separately. RESULTS:
      There were 78 (51%) males and 75 (49%) females. The (mean +/- SD) MMA of mother
      infant pairs at birth were 134.66 +/- 93.31 (95% CI, 119.76 - 149.56) U/ml, and
      187.49 +/- 85.01 (95% CI, 173.91 - 201.07) U/ml, and their correlation was
      significant (p = 0.025). Ninety one (59.5 %) mothers had low Hb, 62 (40.5 %) had
      acceptable Hb levels. The overall mean maternal Hb was 11.01 +/- 1.00 (95% CI,
      10.85 - 11.17) g/dl . A positive significant correlation was observed between
      maternal Hb and MMA of the newborn-infant (p = 0.031). The MANOVA showed a
      statistically significant difference between maternal Hb on the combined
      dependent variables (p =0.033); however, results for the dependent variables
      using the Benferroni adjusted Univariate analysis was significant for only MMA of
      the infants, (p = 0.009). CONCLUSION: There was a significant association between
      aacceptable levels of maternal Hb and high MMA of the newborn-infants. Therefore,
      these newborn infants start out with higher MMA that could give them better
      protection against measles during infancy.

PMID- 24940318
TI  - Seroprevalence of HBV and HIV co-infection in children and outcomes following
      highly active antiretroviral therapy (HAART) in Uyo, South-South Nigeria.
AB  - BACKGROUND: Human Immunodeficiency Virus/Hepatitis B Virus (HIV/HBV) co-infection
      in Nigerian children has emerged as a major concern with the advent of HAART. Its
      impact on the immune system and liver has not been extensively studied in
      children. OBJECTIVES: To determine the prevalence of HBV seropositivity among HIV
      positive children on HAART and its effect on immune response and liver enzymes.
      METHODS: All consecutive HIV positive children aged two months to seventeen years
      on HAART constituted the study population. Age and gender; CD4+ count, ALT,
      creatinine and HBsAg were tested and documented at enrolment and 12months.
      RESULTS: One hundred and seventy one patients were seen over this period. Seventy
      two (43.4%) were males while 94 (56.6%) were females giving a male: female ratio
      of 1:1.3. The mean age of the patients was 63+/-43.4 months. Prevalence of
      HIV/HBV co-infection was 6.02% (95% CI 2.4-9.7). There was no significant effect
      of HBV status on elevation of ALT levels with 12 months of HAART. Co-infected
      patients had an odds ratio of achieving immune response of 0.14 (95% CI 0.02
      0.79). CONCLUSION: HIV/HBV co-infection rates in our children are comparable to
      other localities. ALT levels do not worsen with HAART and immune response of the
      co-infected children on HAART is lower.

PMID- 24940319
TI  - Utilisation of insecticide treated nets among pregnant women in Gulu: a post
      conflict district in northern Uganda.
AB  - BACKGROUND: Malaria during pregnancy causes severe anaemia, placental malaria or
      death to the mother while the fetus may be aborted or stillborn. OBJECTIVE: To
      establish the prevalence and factors associated with Insecticide Treated Net
      (ITN) utilisation among pregnant women in a post conflict Internally Displaced
      Persons (IDP) camps of Gulu district. METHODS: We conducted cross-sectional study
      in 20 IDP camps in which 769 pregnant women were interviewed for ITN utilisation
      the night before the survey. The 20 IDP camps were selected using simple random
      sampling technique as clusters. Households that had pregnant women were then
      consecutively selected. Data were entered in EpiData 3.1 and analyzed using
      STATA11. RESULTS: 35% of pregnant women (95% CI 31% - 38%) had utilised ITNs.
      Factors that promoted ITN utilisation includes: antenatal visit (AOR 1.90, p
      value 0.000); ITN awareness (AOR 1.57, p-value 0.011), and willingness to
      purchase ITN (AOR 2.12, p-value 0.000). Factors which hinder ITN utilisation
      were: hours taken to reach health centre (AOR 0.64, p-value 0.050) and being
      single/widow/divorced (AOR 0.22, p-value 0.000). CONCLUSION: Majority of the
      respondents were not utilising ITN. Therefore, leaders in Gulu district should
      encourage pregnant woman to acquire and use ITN to reduce their vulnerability to
      malaria.

PMID- 24940320
TI  - Synergistic effect of aqueous extract of Telfaria occidentalis on the biological
      activities of artesunate in Plasmodium berghei infected mice.
AB  - BACKGROUND: Resistance to most antimalarial drugs has encouraged the use of
      herbal preparations along with prescribed orthodox drugs. OBJECTIVE: To
      investigate effect of co-administration of aqueous extract of T. occidentalis
      leaves; commonly used as antimalarial and haematinic agent in Nigeria and
      artesunate using P. berghei animal model. METHODS: In vivo curative
      antiplasmodial effect of T. occidentalis (200mg/kg) alone and combination with
      artesunate (2mg/kg) were evaluated using albino mice infected with 10(6)
      parasitized erythrocytes of P. berghei intraperitoneally. The haematological
      parameters: haemoglobin level, red blood cells and white blood cells and packed
      cell volume were monitored using standard methods. RESULTS: Aqueous extract of T.
      occidentalis, artesunate and the combination gave 72.17+/-4.07%, 70.43+/- 4.27%
      and 85.43+/-3.65% reduction in parasitaemia after 48hours respectively. A
      significant enhancement of the PCV was obtained with the coadministration of
      artesunate and aqueous extract (p< 0.01). Similar trends were also observed with
      heamatological parameters at 72hours of administration. CONCLUSION: This study
      revealed a synergistic effect of the co-administration on parasite clearance rate
      of P. berghei infection in mice, with a significant enhancement of haematological
      parameters within 48 hours of administration. This indicates a rapid rate of
      recovery from plasmodial infections with the co-administration.

PMID- 24940321
TI  - Causes and outcome of hospitalization among HIV-infected adults receiving
      antiretroviral therapy in Mulago hospital, Uganda.
AB  - BACKGROUND: Cohorts describing cause specific mortality in HIV-infected patients
      initiating antiretroviral therapy (ART) operate on an outpatient basis.
      Hospitalized patients represent the spectrum and burden of severe morbidity and
      mortality in patients on ART. OBJECTIVE: To determine the causes and outcomes of
      hospitalization among adults receiving ART. METHODS: A prospective cohort study.
      We enrolled 201 participants (50% female) with median (IQR) age and CD4 count of
      34 (28-40) years and 91(29-211) cells/uL respectively. RESULTS: The most frequent
      causes of hospitalization were tuberculosis (TB) (37, 18%), cryptococcal
      meningitis (22, 11%), zidovudine (AZT) - associated anemia (19, 10%), sepsis (10,
      5%) and Kaposi's sarcoma (10, 5%). Forty two patients (21%) died: 10 (24%) had
      TB, 8 (19%) had cryptococcal meningitis and 5 (12%) had sepsis, 9 (21%) had
      undiagnosed neurological syndromes while 10 (24%) had other illnesses. Predictors
      of death included low Karnofsky performance score of < 40 (OR, 21.1; CI 1.43-
      31.6) and age >34 years (OR, 7.65; CI 1.09- 53.8). CONCLUSIONS: Opportunistic
      infections, malignancy and AZT-associated anemia contributed to most
      hospitalizations and mortality. It is important to intensify prevention,
      screening, and treatment for these opportunistic diseases and early ART
      initiation in HIV-infected patients. Tenofovir-based regimens, unless
      contraindicated should be scaled up to replace AZT-based regimens as first line
      ART drugs.

PMID- 24940322
TI  - Stereotypes on Nodding syndrome: responses of health workers in the affected
      region of northern Uganda.
AB  - BACKGROUND: Nodding Syndrome is a debilitating disorder of yet unknown etiology
      that has affected children and adolescents aged 3 - 18 years in parts of sub
      Saharan African countries including Uganda, South Sudan, Tanzania and Liberia.
      OBJECTIVE: To identify stereotypes and negative attitudes held by primary care
      health workers about nodding syndrome. METHOD: Of one hundred health workers
      invited by the Uganda Ministry of Health for training on nodding syndrome from
      the three most affected districts of Pader, Lamwo and Kitgum forty were
      interviewed using a predesigned tool. Content and thematic analysis was applied.
      RESULTS: There were 22 females. The median age was 33 years (range 23-54 years).
      The participants included Psychiatric Clinical Officers, Medical Clinical
      Officers, Laboratory Technicians, Midwives, Registered and Enrolled Nurses.
      Overall, four broad categories of negative stereotypes were identified; Nodding
      syndrome is 1) an incurable disease, 2) is associated with evil spirits and
      curses, 3) is disabling, making the patient a burden to society and 4) is a fatal
      illness. CONCLUSION: Primary health care workers who lead the care of patients
      with nodding syndrome have several negative stereotypes that may potentially
      impact negatively on the quality of care they provide.

PMID- 24940323
TI  - Factors influencing urban malaria: a comparative study of two communities in the
      Accra Metropolis.
AB  - BACKGROUND: As urban centres in Ghana continue to grow, the scale and impact of
      urban malaria is increasing. OBJECTIVE: To compare the prevalence of malaria in
      two communities and how this may be affected by knowledge, attitudes,
      socioeconomic status and preventive practices of residents in two communities
      within the Accra metropolis. METHODS: Giemsa-stained thick blood films were
      examined for malaria parasites in 400 people (200 each from townships with high
      and low urban status) from May to November 2009. Questionnaires were administered
      to determine and evaluate demographics of the participants. All participants
      lived within the two catchment areas, about 20 km apart. RESULTS: Average malaria
      prevalence among participants was 8.75%. Prevalence in Kaneshie (12%: p=0.032)
      was significantly higher compared to Airport West (5.5%). Illiteracy rate
      (17.5%), self-medication (81.5%) and the use of coils (21.0%) as a control
      mechanism was higher among residents of Kaneshie than Airport West. Most of the
      people (40%) in Kaneshie did not use any form of malaria control method.
      Insecticide spray was the most preferred malaria control mechanism by the Airport
      West residents (60.5%). Overall knowledge about malaria, employment status,
      housing conditions, level of overcrowding and the cost of treatment of malaria
      was better in Airport West than at Kaneshie. CONCLUSION: Malaria prevalence and
      factors influencing its transmission differs within communities in the same urban
      area. It is therefore essential to develop control and prevention strategies
      based on the needs of specific communities.

PMID- 24940324
TI  - Effects of intravenous diclofenac on postoperative sore throat in patients
      undergoing laparoscopic surgery at Aga Khan University Hospital, Nairobi: a
      prospective, randomized, double blind controlled trial.
AB  - BACKGROUND: postoperative sore throat is the commonest complication after
      endotracheal intubation. The efficacy of intravenous non-steroidal anti
      inflammatory drugs in alleviating postoperative sore throat has not been
      investigated. OBJECTIVE: To evaluate the effect of intravenous diclofenac sodium
      on the occurrence and severity of postoperative sore throat. METHODS: 42 in
      patients scheduled for laparoscopic surgery were randomized into two equal groups
      to receive either a single dose of 75mg intravenous diclofenac sodium in addition
      to standard treatment taken at our hospital for the prevention of postoperative
      sore throat or to receive standard treatment only. All patients were interviewed
      postoperatively at 2, 6 and 18 hours. Data of the baseline characteristics, the
      incidence and severity of sore throat were collected. If sore throat was present,
      a Visual Analogue Score was used to assess its severity. RESULTS: the baseline
      characteristics of the participants were similar. The majority of the patients
      undergoing laparoscopic surgery were women. There was no statistically
      significant difference in the occurrence or severity of postoperative sore throat
      between the diclofenac and standard treatment groups at 2, 6 and 18 hours
      postoperatively. CONCLUSION: Intravenous diclofenac sodium does not reduce the
      occurrence or severity of postoperative sore throat.

PMID- 24940325
TI  - Risk factors for un-investigated dyspepsia among primary care patients in
      northern Nigeria.
AB  - BACKGROUND: Many risk factors have been speculated to be associated with
      uninvestigated dyspepsia amongst different population groups. Some of which have
      been subjected to epidemiological survey while others remain unevaluated.
      OBJECTIVE: We evaluated some of the documented risk factors amongst patient
      presenting with uninvestigated dyspepsia and compared with a matched group
      without dyspepsia in a primary care setting. METHODS: The study was a matched
      case controlled study. 103 consecutive patient aged between 18 and 50 years that
      presented with dyspepsia (cases) were enrolled. These were matched by age and sex
      with the same number of subjects without dyspepsia (controls). Data were collated
      using a structured questionnaire Odds ratios and p-values were used to determine
      the significance of documented categorical risk factors associated with dyspepsia
      using two by two tables. For risk factors that were continuous variables the
      means, standard deviations and p-values were used. Risk factors with their p
      values <0.2 were entered into logistic regression to identify those independently
      associated with dyspepsia. RESULT: H.pylori seropositivity was 22.3% and 13.6%
      among cases and controls respectively (p = 0.10). Pepper intake (p <0.0001) and
      tea intake (p = 0.0002) and greater years of education (p = 0.0065) were
      significantly associated with dyspepsia. H. pylori seropositivity was not related
      to the risk of developing dyspepsia. CONCLUSION: Helicobacter pylori
      seropositivity was not found to be a significant contributor to risk of
      developing dyspepsia among the studied population contrary to general belief.
      Pepper intake, tea intake and greater years of education were found to
      significant contributors to dyspepsia.

PMID- 24940326
TI  - Determinants of HIV testing among young people aged 18 - 24 years in South
      Africa.
AB  - BACKGROUND: Although recent estimates of the HIV/AIDS burden in South Africa show
      the particular vulnerability of youth to HIV, HIV testing and its determinants
      are largely understudied in this age group. OBJECTIVE: To investigate the
      prevalence and determinants of HIV testing among young people aged 18 to 24
      years, as part of an evaluation of the impact of loveLife. METHODS: South
      Africa's national HIV prevention campaign for young people, on HIV and related
      risk behaviours. A cross-sectional population-based household survey was
      conducted using a multistage stratified cluster sampling approach. The total
      sample included 3123 participants, aged 18-24, 54.6% men and 45.4% women, from
      four provinces (Eastern Cape, Gauteng, KwaZulu-Natal and Mpumalanga). RESULTS:
      The results indicated that over half (52.2%) of the youth reported testing for
      HIV, with more young females (60.1%) testing for HIV compared to their male
      counterparts (39.9%). In the multivariate analysis, older age, being female, HIV
      knowledge, having ever talked to the mother or female guardian about HIV and
      having ever been pregnant or made someone pregnant were found to be associated
      with testing for HIV. CONCLUSION: There is still room for improving the low
      proportion of young people who test for HIV. Specific attention needs to be paid
      to younger males, with lack of HIV knowledge, having never talked to the mother
      or female guardian about HIV and having never been pregnant or made someone
      pregnant were less likely to be tested. Outreach at individual and community
      levels and public health messages targeting these youth should be implemented.

PMID- 24940327
TI  - Factors associated with injuries among first-division Rwandan female soccer
      players.
AB  - BACKGROUND: Female soccer has grown tremendously in the last decade. Studies have
      suggested that female soccer players are more susceptible to injuries than their
      male counterparts, and their vulnerability is due mainly to intrinsic factors
      such as their anatomical and physiological structure. OBJECTIVES: To establish
      factors associated with soccer injuries among first-division Rwandan female
      soccer players. METHODS: In a descriptive cross-sectional study, self
      administered questionnaires were used to investigate factors associated with
      injuries among soccer players. RESULTS: Almost half of the 300 participants (45%)
      indicated having been injured in the three seasons prior to the study. More than
      half (52.6%) were recurrent injuries. The ankle was the most common body part
      injured. Intrinsic factors associated with injuries were age, excessive ankle
      range of motion, pre-menstrual symptoms, and previous injury (p-value < 0.05).
      Extrinsic factors associated with injuries were use of oral contraceptive pills,
      (OCP), competition level, use of protective equipment, and player's position.
      CONCLUSIONS: The large number of recurring injuries was notable, emphasizing the
      importance of prevention strategies and access to adequately trained medical
      personnel as research has shown a significant reduction in the prevalence of
      recurring injuries after the introduction of effective prevention programmes.

PMID- 24940328
TI  - Knowledge, attitudes & barriers to condom use among female sex workers and truck
      drivers in Uganda: a mixed-methods study.
AB  - BACKGROUND: There is limited documentation on knowledge, attitudes and barriers
      to condom use among female sex workers (FSWs) and truck drivers (truckers).
      OBJECTIVE: To explore knowledge, attitudes and barriers to condom use among FSWs
      and truckers operating along major transport corridors in Uganda. METHODS:
      Structured questionnaires were administered to explore FSWs' and truckers'
      knowledge of and attitudes towards condom use among 259 FSWs and 261 truckers.
      Qualitative data were collected on barriers to condom use using focus group
      discussions. Quantitative data were analyzed using SPSS while qualitative data
      were audio-recorded, transcribed and thematically analyzed. RESULTS: Condom
      knowledge was high with 97% of FSWs and 95% of truckers agreeing with the
      statement, "using condoms properly and consistently reduces risk of HIV
      infection". Attitudes towards condom use were generally favorable with 91% of
      FSWs and 82% of truckers agreeing with the statement, "condom use is the best
      method of HIV prevention". Qualitative findings show that poverty, refusal to use
      condoms by male partners, alcohol use before sex and beliefs that condoms 'kill
      the mood for sex' remain key barriers to consistent condom use. CONCLUSIONS:
      Consistent condom use among FSWs and truckers is still hampered by economic and
      relationship factors.

PMID- 24940329
TI  - Evaluation of some anthropometric indices for the diagnosis of obesity in
      pregnancy in Nigeria: a cross-sectional study.
AB  - BACKGROUND: Obesity in pregnancy is a global health problem which is associated
      with poor pregnancy outcomes. The use of weight and height, measured at about ten
      weeks of gestation, to produce pre-gestational body mass index is recommended for
      the diagnoses of the condition but limitations abound in under resourced
      settings. OBJECTIVES: To measure anthropometric indices such as mid upper arm
      circumference, calf circumference, waist circumference and waist to hip ratio,
      for identification of obesity in pregnancy. METHODS: Anthropometric measurements
      were carried out on cohorts of pregnant women from 4 hospitals in Enugu, South
      eastern Nigeria. RESULTS: There were no significant difference in the mean mid
      upper arm circumference (MUAC) and calf circumference (CC) across the trimester
      groups. The mean values of waist circumferences, hip circumference and waist to
      hip ratios changed significantly across the trimesters. The 75(th) percentile of
      MUAC (33 cm) and CC (39 cm) in all trimesters, had sensitivity and specificity of
      more than 70% for identifying obesity in pregnancy. CONCLUSION: MUAC and CC
      values of 33cm and 39cm respectively might be reliable cut off points for
      diagnoses of obesity throughout pregnancy in Enugu, Nigeria.

PMID- 24940330
TI  - Knowledge about the research and ethics committee at Makerere University,
      Kampala.
AB  - BACKGROUND: All research involving human participants should be reviewed by a
      competent and independent institutional research and ethics committee. Research
      conducted at Makerere University College of Health Sciences should be subjected
      to a rigorous review process by the ethics committee in order to protect human
      participants' interests, rights and welfare. OBJECTIVE: To evaluate researchers'
      knowledge about the functions and ethical review process of the College of Health
      Sciences research and ethics committee. METHODS: A cross sectional study. 135
      researchers consented to participate in the study, but 70 questionnaires were
      answered giving a 52% response. RESULTS: Age ranged between 30 to 61 years,
      majority of participants 30-39 years. Most of the respondents do agree that the
      REC functions include Protocol review 86%, protection of research participants
      84.3%, and monitoring of ongoing research. During ethical review, the RECpays
      special attention to scientific design [79.7%] and ethical issues [75.3%], but
      less to the budget and literature review. More than 97% of the respondents
      believe that the REC is either average or very good, while 2.8% rank it below
      average. CONCLUSION: Respondents knew the major functions of the committee
      including protection of the rights and welfare of research participants, protocol
      review and monitoring of on going research, and the elements of protocol review
      that are given more attention include ;scientific design and ethical issues.
      Overall performance of the REC was ranked as average by respondents. The
      committee should limit delays in approval and effectively handle all functions of
      the committee.

PMID- 24940331
TI  - Sexually transmitted infections and their diagnoses: Bapedi experience.
AB  - BACKGROUND: The global burden of sexually transmitted infections (STIs) is a
      major concern to the World Health Organization (WHO). OBJECTIVE: To document STIs
      treated by Bapedi traditional healers and their methods of diagnoses in the
      Limpopo Province, South Africa. METHODS: A semi-structured questionnaire with
      closed and open-ended questions was used to collect data from 34 traditional
      healers, during a face-to-face interview. RESULTS: Five seemingly dissimilar
      STIs; gonorrhoea, chlamydia, HIV/AIDS, nta (Bapedi-terminology) and syphilis were
      identified as being treated by Bapedi traditional healers. With the exclusion of
      HIV/AIDS, all STIs are known by healers via their vernacular names. Not all of
      the recorded STIs are treated by all the questioned traditional healers.
      Generally, diagnosis of these infections was based primarily on the presentation
      of symptoms and certain behavioural traits; mostly unprotected sexual intercourse
      with multiple partners. CONCLUSION: The current study concludes that Bapedi
      traditional healers play an important role in the treatment STIs in the Limpopo
      Province. Of concern is their diagnosis which is based primarily on the
      presentation of symptoms and behavioural traits, which are not always accurate
      indicators. Thus, to make their contribution to the treatment and management of
      STIs beneficial, they have to receive elementary training in diagnostic methods
      particularly for HIV/AIDS.

PMID- 24940333
TI  - The effect of experimental streptococcus infection in myocarditis on some
      biochemical and inflammatory markers in albino rats.
AB  - BACKGROUND: Myocarditis is an uncommon disease that presents with a wide range of
      symptoms in children and adults. It is histologically characterized by varying
      degrees of myocardialnecrosis, edema and cellular infiltration myocardial
      inflammation is a nonspecificresponse to many triggers such as bacterial
      infection, cardio toxic agents, ormechanical injury. OBJECTIVE: This study was
      carried out to investigate the experimental Streptococcus faecalis induction of
      myocarditis and its effect on some blood parameters, inflammatory markers and
      histopathological changes in male albino rats. METHODS: Rats were infected by
      intraperitoneal injection of 10 8 CFU/ml of Streptococcus faecalis and sacrificed
      after one, two and seven days post infection. Biochemical analyses of blood were
      carried out to investigate the serum biomarkers of inflammation, liver function
      tests, cardiac enzymes & kidney function tests. RESULTS: All biochemical analyses
      showed statistically significant increase in the measured parameters due to
      bacterial infections except for blood urea which appear to be normal. A
      significant positive correlation was observed between lactate dehydrogenase
      enzyme (LDH) with creatinine (r =0.778, P<0.01). In the 7 days group, there were
      significant positive correlations between aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) (r=0.675, P<0.05), erythrocyte sedimentation rate
      (ESR) with Urea (r=0.659, P<0.05) and alkaline phosphatase (ALP) with C-reactive
      protein (CRP) (r=0.765, p<0.01). CONCLUSION: Many of these biomarkers will
      provide important new insights into pathophysiology and aid in the diagnosis and
      management of cardiovascular patients.

PMID- 24940332
TI  - Assessment of psychological barriers to cervical cancer screening among women in
      Kumasi, Ghana using a mixed methods approach.
AB  - BACKGROUND: Cervical cancer is the leading cause of cancer death among women in
      Ghana, West Africa. The cervical cancer mortality rate in Ghana is more than
      three times the global cervical cancer mortality rate. Pap tests and visual
      inspection with acetic acid wash are widely available throughout Ghana, yet less
      that 3% of Ghanaian women get a cervical cancer screening at regular intervals.
      OBJECTIVE: This exploratory study was to identify psychological barriers to
      cervical cancer screening among Ghanaian women with and without cancer using a
      mixed methods approach. METHODS: Semi-structured interviews were conducted with
      49 Ghanaian women with cancer and 171 Ghanaian women who did not have cancer.
      RESULTS: The results of the quantitative analysis indicated that cancer patients
      where not more likely to have greater knowledge of cancer signs and symptoms than
      women without cancer. Analysis of the qualitative data revealed several
      psychological barriers to cervical cancer screening including, common myths about
      cervical cancer, misconceptions about cervical cancer screening, the lack of
      spousal support for screening, cultural taboos regarding the gender of healthcare
      providers, and the stigmatization of women with cervical cancer. CONCLUSION: The
      results of this study can be used to inform the development of culturally
      relevant cervical cancer education interventions aimed at addressing the
      psychological barriers to cervical cancer screening perceived by Ghanaian women.

PMID- 24940334
TI  - Knowledge and attitudes of infection prevention and control among health sciences
      students at University of Namibia.
AB  - BACKGROUND: Health Sciences students are exposed early to hospitals and to
      activities which increase their risk of acquiring infections. Infection control
      practices are geared towards reduction of occurrence and transmission of
      infectious diseases. OBJECTIVE: To evaluate knowledge and attitudes of infection
      prevention and control among Health Science students at University of Namibia.
      METHODS: To assess students' knowledge and attitudes regarding infection
      prevention and control and their sources of information, a self-administered
      questionnaire was used to look at standard precautions especially hands hygiene.
      RESULTS: One hundred sixty two students participated in this study of which 31
      were medical, 17 were radiography and 114 were nursing students. Medical students
      had better overall scores (73%) compared to nursing students (66%) and radiology
      students (61%). There was no significant difference in scores between sexes or
      location of the high school being either in rural or urban setting. CONCLUSION:
      Serious efforts are needed to improve or review curriculum so that health
      sciences students' knowledge on infection prevention and control is imparted
      early before they are introduced to the wards.

PMID- 24940335
TI  - Changes in platelet functional parameters and CD62 P expression in liver
      cirrhosis.
AB  - BACKGROUND: Hepatic impairment, portal hypertension, and multi-systemic damage
      could occur during liver cirrhosis's late stage. Bleeding is a complication of
      hepatic cirrhosis along with several changes including blood platelet count
      (BPC), mean platelet volume (MPV), platelet crit (PCT) and expression of platelet
      CD62P. Blood platelet count (BPC), mean platelet volume (MPV), platelet
      distribution width, and other indices are indirect reflections of CD62P
      parameters. OBJECTIVE: To investigate the changes in platelet functional
      parameters and CD62 P expression in liver cirrhosis as a possible guide in
      clinical treatments and prognoses of liver cirrhosis. METHODS: CD62P was tested
      by flow cytometry in liver cirrhosis. BPC, MPV, and PCT in peripheral blood were
      tested using an auto blood cell analyzer. Data were analyzed using SPSS11.0.
      RESULTS: The values of CD62P and MPV in patients was significantly higher than
      those of healthy donors (P<0.01), while the values of BPC and PCT were
      significantly lower than those of the control group (P<0.01). CONCLUSIONS: CD62P,
      BPC, MPV, and platelet crit (PCT) show several changes in liver cirrhosis. It is
      useful to understand the relationship between hepatic cirrhosis severity and
      CD62P, BPC, MPV, PCT, timely monitoring of CD62P for treatment of hepatic
      cirrhosis in clinical treatment and prognosis.

PMID- 24940336
TI  - Antihypercholesterolemic activity of ethanolic extract of Buchholzia coriacea in
      rats.
AB  - BACKGROUND: Hypercholesterolemia is a condition characterised with high level of
      cholesterol in the blood. OBJECTIVES: The effect of ethanolic extract of
      Buchholzia coriacea (EEBC) on the lipid profile levels and extent of lipid
      peroxidation in hypercholesterolemic albino rats was investigated in this study.
      METHODS: Thirty albino rats were divided into six different groups which consist
      of group 1 (control), group 2 (hypercholesterolemic rats), group 3
      (hypercholesterolemic rats treated with ethanolic extract of EEBC), group 4
      (hypercholesterolemic rats treated with questran), group 5 (normal rats treated
      with EEBC) and group 6 (normal rats treated with questran). The rats were
      sacrificed at the end of the sixth week and assay conducted for Aspartate
      Transaminase (AST), Alanine Transaminase (ALT), lipid profile and biomarker of
      oxidative stress. RESULTS: The serum and liver total cholesterol and LDL -
      cholesterol levels as well as lipid peroxidation in the EEBC-treated
      hypercholesterolemic rats were significantly reduced (p < 0.05) when compared
      with the untreated hypercholesterolemic rats. The activities of AST and ALT in
      EEBC - treated hypercholesterolemic rats were not significantly different (p >
      0.05) from the control. CONCLUSIONS: The results suggest that Buchholzia coriacea
      seeds contain potent antihypercholesterolemic agent which may find clinical
      application in ameliorating hypercholesterolemia and its attendant complications.

PMID- 24940337
TI  - Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta
      lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in
      Abeokuta, South western, Nigeria.
AB  - BACKGROUND: The increased reports of ESBL dissemination from various centres in
      south western, Nigeria and the recent emergence of carbapenem resistant bacteria
      prompted the conception of this study. OBJECTIVES: To demonstrate the
      relationship between high molecular weight plasmids and the expression of
      antibiotic multi-resistance including ESBL and carbapenemase. METHODS: We
      investigated 97 isolates of selected organisms consisting of 67 E. coli and 30
      Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem
      hydrolysing enzymes. Beta-lactamase was determined using acidometric method,
      while ESBL and carbapenemase activity was determined using the double-disk
      diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL
      and carbapenemase positive isolates were determined according to standard
      protocols. RESULTS: An ESBL prevalence rate of 21.6% and carbapenem- resistance
      rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates
      showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin.
      Moderate susceptibility was recorded against the Quinolone class of antibiotics;
      Meropenem remained the most active antibiotic against ESBL isolates with 62.5%
      against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study
      isolates ranged from 11.8kbp to 35.5kbp. CONCLUSION: Due to the relationship
      between high molecular weight plasmids and multi-drug resistance, we hereby
      recommend regular molecular surveillance of this form in our study setting.

PMID- 24940338
TI  - Enteroviruses as a possible cause of hypertension, dilated cardiomyopathy (DCM)
      and hypertensive heart failure (HHF) in South western Nigeria.
AB  - BACKGROUND: Human enteroviruses have long been associated with various diseases
      of man resulting into a wide range of acute symptoms involving the cardiac and
      skeletal muscles, central nervous system, pancreas, skin and mucous membranes.
      OBJECTIVE: To assess the role of enteroviruses in the etiology of hypertension,
      DCM and HHF. METHODS: We obtained stool specimens from 70 subjects comprising 65
      patients and 5 controls and isolation was carried out on RD, L20B, HEp-2C and
      Vero cell lines and identified by neutralization with standard antisera (RIVM).
      Thirty-six enteroviruses were isolated and identified to be Coxsackieviruses-B5,
      A9, Echoviruses 1, 6, 7, 9, 11, 12, 22, 30 and Poliovirus type 1 and 3. RESULTS:
      Three most frequently occurring enterovirus serotypes which constitute 60.0% of
      the 30 NPEV typed and 50.0% of all the isolates were Echoviruses, Coxsackie-B5
      virus and Coxsackievirus-A9. Echoviruses constituted 50.0% of all the serotypes
      while Coxsackieviruses-B5 and A9 accounts for the 27.8 % and 5.6% respectively.
      Enteroviral isolation rate was higher in age groups 51 years and above. The
      percentage of study subjects who had Coxsackie-B5-viruses and echoviruses was
      significantly (P<0.05) higher in cases of hypertension, HHF and DCM than in
      control subjects. Coxackie-B5-virus, Echovirus-6 and Echovirus-11 were found in
      both study locations. CONCLUSION: The findings of this study showed that
      Enteroviruses may likely be involved in the etiology of hypertension, DCM and
      HHF. Further studies would therefore be necessary for the prevention and control
      of these diseases.

PMID- 24940340
TI  - Attitude of Lesotho health care workers towards HIV/AIDS and impact of HIV/AIDS
      on the population structure.
AB  - BACKGROUND: The impact and management of HIV/AIDS in Lesotho in the context of
      disaster management was investigated. OBJECTIVES: Lesotho health care workers'
      perception on HIV/AIDS progression, whether HIV/AIDS was managed as a disaster,
      and the impact on the demographic profile was investigated. METHODS: The
      empirical investigation included a literature study, and primary and secondary
      data analyses. Questionnaires (n=116) determined health care workers' perception
      of HIV/AIDS. Interviews with officers of Lesotho Disaster Management determined
      how HIV/AIDS was managed as a disaster. National population censuses and data
      from surveys were summarised to describe the impact of HIV/AIDS on the population
      structure. RESULTS: Respondents' modal age group was 25 to 39 years, 28.4% viewed
      HIV/AIDS related deaths as very high and perceived that HIV/AIDS changed the age
      composition, sex and dependency ratio of the population. Although HIV/AIDS was
      declared a disaster, the Lesotho Disaster Management Authority only aided the
      National AIDS Commission. There was evidence that HIV/AIDS caused the population
      pyramid base to shrink, and an indentation in the active population. CONCLUSION:
      Health care workers attributed HIV/AIDS to changing the demographic profile of
      Lesotho, also reflected in the population pyramid. Lesotho Disaster Management
      Authority played a supporting role in HIV/AIDS disaster management.

PMID- 24940339
TI  - Dyslipidaemia and dysglycaemia in HIV-infected patients on highly active anti
      retroviral therapy in Kumasi Metropolis.
AB  - BACKGROUND: Diet and genetic predisposition significantly affect lipid metabolism
      in the individual. This metabolic effect is further challenged in patients
      infected with HIV and on HAART. The prolonged use of HAART is associated with
      lipodystrophy, dyslipidemia, and insulin resistance. OBJECTIVE: To determine the
      prevalence of lipid dysregulation and dysglycaemia in HIV infected patients on
      HAART in the Kumasi metropolis. METHODS: This cross sectional study was conducted
      between October 2009 and June 2010, and 305 HIV-infected patients consisting of
      164 patients on HAART for at least six months and 141 HAART-naive patients
      constituted HIV-positive patients, not on HAART and whose CD4 were not below 320
      cell/ml as the control. Data was analyzed using Graph Pad Prism (version 5.0).
      Unpaired t-test, linear and multivariate regression analyses, was used to predict
      glucose level from the various parameters. Anthropometric parameters consisting
      of body weight, waist and hip circumferences, height, bicep and triceps skin fold
      were measured with a pair of calipers. Lipid profile and fasting blood glucose
      were determined by enzymatic methods. CD4 counts and hemoglobin were determined.
      RESULTS: Fasting plasma, glucose (3.81+/-0.08mmol/l, 4.48+/-0.17mmol/l), total
      cholesterol (3.05+/- 0.0 8mmol/l, 4.54+/-0.08mmol/l) LDL (2.24+/-0.07mmol/l,
      2.87+/-0.07mmol/l) and HDL (0.85+/-0.04mmol/l, 0.97+/-0.03mmol/l) between the
      control and case respectively were significantly raised (P< 0.001), though within
      the physiological range. The significantly increased hip and waist
      circumferences, waist-to-hip ratio (0.85+/-0.22, 0.88+/-0.01) of the control and
      case correlated with lipodystrophy. CONCLUSION: HAART was associated with
      lipodystrohy and, the risk of developing type II diabetes among the HAART
      experienced group was 5 times higher than the HAART naive group.

PMID- 24940341
TI  - The pattern and challenges of infertility management in Lagos, Nigeria.
AB  - BACKGROUND: Infertility remains a threat to successful reproduction by couples
      desirous of pregnancy. OBJECTIVE: To determine the pattern of infertility cases
      amongst infertile couples seeking care in Lagos University Teaching Hospital as
      well as challenges in their management. METHODS: A review of the management of
      couples referred for infertility to the gynaecological outpatient clinic of the
      Lagos University Teaching Hospital (LUTH), Nigeria from 1(st) January 2005 to
      31(st) December 2006. RESULTS: The incidence of infertility was found to be 26.8%
      of the gynaecological consultations with a mean duration of infertility of 4.3 +/
      3.4 years. The mean age of the women was 33.8 +/- 5.2 years and 66.1% were
      nulliparous. Secondary infertility accounted for 80% of cases. Male factors only
      was the cause in 11.1%, female factor only in 37.8%, both male and female factors
      in 40% while no cause was identifiable in 11.1%. There was no association between
      tubal occlusion and a history of induced abortion in this study (p >0.05). There
      was a high rate of discontinuation of care by their large numbers lost to follow
      up. CONCLUSION: Infertility is still a public health problem in Lagos, Nigeria.

PMID- 24940342
TI  - Vitamin D intake and type 2 diabetes risk: a meta-analysis of prospective cohort
      studies.
AB  - BACKGROUND: The findings form studies on the relationship between vitamin D and
      type 2 diabetes were inconsistent. OBJECTIVES: To elucidate the association
      between vitamin D consumption and type 2 diabetes risk by conducting a meta
      analysis. METHODS: We conducted a systematic literature search to identify
      prospective cohort studies of vitamin D intake and type 2 diabetes risk prior to
      November 2012. Eligible studies were retrieved via both computer searches and
      manual review of references. The summary risk estimates were calculated based on
      the highest versus the lowest categories. RESULTS: Meta-analysis of 4 prospective
      cohort studies involving 187, 592 participants and 9, 456 incident cases showed
      an absence of significant association between total vitamin D intake and type 2
      diabetes risk. The combined RR was 0.93 (95% CI: 0.85-1.01). The associations
      were similar for subgroup analyses, a combined RR respectively was 0.94 (95% CI:
      0.77-1.08), 0.91 (95% CI: 0.77-1.08), 0.93 (95% CI: 0.84-1.02), and 0.92 (95% CI:
      0.84-1.01) for the intake of dietary vitamin D, supplemental vitamin D, total
      vitamin D in USA and total vitamin D for women only. CONCLUSIONS: Our results
      support that there was no association between vitamin D intake and type 2
      diabetes.

PMID- 24940343
TI  - Hepatitis B surface antigenemia (HBsAg) among pregnant women in southern Nigeria.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is one of the most common public
      health problems worldwide. Over one million people die annually of HBV- related
      chronic liver disease. Maternal to fetal transmission from chronic carriers
      exceeds 90% and accounts for up to 40% of the world's chronic carriers in endemic
      areas. METHODS: This was a descriptive study which involved Serial recruitment of
      836 women attending the antenatal clinic at a health facility in Cross-River
      State, Nigeria from 1(st) January to 30(th) June 2010. HBsAg screening was done
      using an ELISA test. RESULTS: Fifty five (6.6%) of the 836 women screened tested
      positive for HBsAg. The mean age and parity of sero-positive subjects was 26.9 +/
      5.0 (range 18-38 years) and 2.2+/-1.2 (0 to 5) respectively. The prevalence was
      more in women who were farmers (29.1%) and those with either none or low level of
      formal education (67.2%). CONCLUSION: Sero-prevalence of 6.6% among pregnant
      women is reported. Women education, economic empowerment and public enlightenment
      programmes focused on modification of risky social lifestyle is recommended.
      Efforts to promote routine screening of pregnant women, immunization and
      vaccination of infants should be sustained.

PMID- 24940344
TI  - Demographic profile and epidemiology of injury in Mthatha, South Africa.
AB  - OBJECTIVE: To determine the magnitude, socio-demographic and epidemiological
      characteristics of injury at a Provincial referral hospital. METHODS: This review
      was conducted on all trauma patients admitted at the Mthatha Hospital Complex and
      Nelson Mandela Academic Hospital from the 1(st) January 1997 to the 31(st)
      December 2000. RESULTS: The incident rate of injuries was 3.2% (n=2460/75,833
      total admissions). Injured patients were mostly black (80%) and males (ratio: 5
      men: 1 woman). Only 8.1% of injured patients were transported to hospital by
      ambulances. The leading causes of injuries were inter-personal violence
      accounting for 60% of cases, and motor vehicle accidents accounting for 19%; of
      them 38% were due to poor visibility, over speeding, and fatigue. The overall
      mortality was 33% (n=821) independently predicted by poverty (OR=8.2 95%CI 6
      11.1; P<0.0001) and age>40 years(OR=7.8 95%CI 7.7-12.1;P<0.0001). CONCLUSION: The
      burden of injury is a mass issue that warrants regional attention with quality of
      care and training.

PMID- 24940345
TI  - Use of antibiotics among non-medical students in a Nigerian university.
AB  - BACKGROUND: Antibiotic misuse is a major contributory factor to treatment
      failure, antibiotic resistance and high healthcare costs. OBJECTIVES: To evaluate
      level of self-reported antibiotic misuse among non-medical undergraduate students
      of a Nigerian university. METHODS: Respondents' knowledge of antibiotics and
      disposal system for left-over antibiotics were explored using a structured
      questionnaire. Data were summarized with descriptive statistics. Chi square was
      used to evaluate relationship between specific categorical variables and
      respondents' opinions with p<0.05. RESULTS: More than half the respondents
      obtained their antibiotics through doctor's prescriptions (273; 68.3%). The study
      revealed gross antibiotic misuse with majority, (298;74.5%) either by keeping
      left-over antibiotics for future use or throwing it away with refuse. Respondents
      (289; 72.3%) sometimes forgot to take the antibiotics. Financial constraints (73;
      18.3%), long duration of treatment (70; 17.5%), side effects experienced
      (60;15.0%), polypharmacy (56;14.0%), tablet size (45;11.3%), and perceived low
      level of confidence in the prescriber (11; 2.8%) were major reasons for non
      adherence. Course of study of respondents had no significant effect on
      respondents' knowledge or adherence (p>0.05). CONCLUSION: Misuse of antibiotics
      among non-medical undergraduate students in a Nigerian university setting is
      pervasive suggesting an urgent need for enlightenment on rational use and
      disposal of antibiotics.

PMID- 24940346
TI  - Bacteriological and physico-chemical quality of drinking water sources in a rural
      community of Ethiopia.
AB  - BACKGROUND: Accesses to safe water is a universal need however, many of the
      world's population lack access to adequate and safe water. Consumption of water
      contaminated causes health risk to the public and the situation is serous in
      rural areas. OBJECTIVES: To assess the bacteriological and physico-chemical
      quality of drinking water sources in a rural community of Ethiopia. METHODS:
      Water samples were collected from tap, open springs, open dug wells and protected
      springs for bacteriological analysis of total coliforms and thermotolerant
      coliforms. The turbidity, pH and temperature were measured immediately after
      collection. RESULTS: Most drinking water sources were found to have coliform
      counts above the recommended national and international guidelines and had high
      sanitary risk scores. There was a statistically significant difference among
      water sources with respect to TC and TTC (p < 0.05) and there was a statistically
      significant positive correlation between coliform counts and sanitary risk scores
      (p < 0.01). Most water sources didn't satisfy the turbidity values recommended by
      WHO. CONCLUSION: The water sources were heavily contaminated which suggested poor
      protection and sanitation practice in the water sources. Source protection
      strategies as well as monitoring are recommend for this community.

PMID- 24940347
TI  - The Obstetrics Gynecology and Children's Hospital Emergency Room waiting time
      before hospitalization.
AB  - BACKGROUND: One of the most substantial factors affecting patient satisfaction in
      the Obstetrics-Gynecology and Children's Hospital is the wait time in the
      emergency room. OBJECTIVE: We retrospectively studied the waiting periods of
      patients visiting the emergency room patients in Bolu Izzet Baysal Obstetrics
      Gynecology and Children's hospital. METHOD: Using an automated documentation
      system for each patient that recorded the season in which the patients consulted
      the emergency room, the month, day, time, examination time, hospitalization
      decision time, the hospitalization clinic following the decision to hospitalize,
      and the time to hospitalization, we retrospectively studied the waiting periods
      of emergency room patients in Bolu Yzzet Baysal Obstetrics-Gynecology and
      Children's Hospital. RESULTS: A total of 15,004 patients who consulted the
      hospital emergency room between November 24, 2009, and August 25, 2011, and who
      were hospitalized in a clinic were included in this study. The highest frequency
      of emergency room patient visits occurred during the summer season (28.1%), in
      the month of July (10.2%), on Mondays (16.1%), and between 8 and 11 AM (22.1%; p
      < 0.05). The emergency room wait time of patients consulting the pediatric clinic
      was (55 +/- 67 min), which was significantly shorter than the wait time of
      patients consulting other clinics (p < 0.05). CONCLUSION: The majority of
      patients who were hospitalized in any clinic through the emergency room consulted
      the hospital during the daytime hours. The time to hospitalization for the
      admitted patients was within an acceptable time frame. We believe that conducting
      comprehensive research to determine whether it is possible to reduce wait times
      even further to increase patient satisfaction will be instructive.

PMID- 24940348
TI  - Stray dog trade fuelled by dog meat consumption as a risk factor for rabies
      infection in Calabar, southern Nigeria.
AB  - BACKGROUND: Rabies is a preventable zoonosis with the highest case fatality of
      any disease in the world. In the developing world, it is transmitted mainly by
      dog bites. In parts of southern Nigeria, dog meat is a delicacy. OBJECTIVE: To
      highlight trade in stray dogs as a major risk factor for rabies in animals and
      humans in south-south Nigeria. METHOD: Patients admitted into the University of
      Calabar Teaching Hospital (UCTH) with a diagnosis of rabies between July and
      October 2012 were analysed for risk factors, post exposure prophylaxis (PEP),
      health seeking behaviour and outcome. Focused group interview were also conducted
      among traders/handlers of stray dogs. RESULTS: Ten cases of rabies in subjects
      aged 3 to 52 years were recorded in these five months period. Eight of the cases
      were male and apparently got infected directly or indirectly through the trade in
      stray dogs for human consumption. None had proper PEP and all patients died.
      CONCLUSION: Stray dog trade, fuelled by eating of dog meat, is a risk factor for
      human and animal rabies in Calabar, southern Nigeria. Culling of stray dogs,
      control of stray dogs' trade and public enlightenment on PEP is recommended.

PMID- 24940349
TI  - Platelet volume evaluation in patients with sepsis: associated factors should be
      considered.

PMID- 24940350
TI  - Mean platelet volume in supraventricular tachyarrhythmia can be affected by many
      cardiovascular risk factors.

PMID- 24940351
TI  - The number of urine specimens for bacteriological examination in women.

PMID- 24940352
TI  - Bacteriuria in diabetes mellitus patients in Cameroon: number of urine specimens
      in women.

PMID- 24940353
TI  - Infections and non-communicable diseases that just refuse to go away.

PMID- 24940354
TI  - Psychosocial distress and functioning of Greek youth with cystic fibrosis: a
      cross-sectional study.
AB  - BACKGROUND: To assess psychosocial functioning and distress of children and
      adolescents with cystic fibrosis compared to healthy controls. METHODS: Thirty
      six patients with cystic fibrosis aged 8-18 years (24 boys, mean age +/- SD: 11.5
      +/- 2.6 years) and 31 sex- and age-matched healthy control subjects (18 boys,
      mean age +/- SD: 12 +/- 2.5 years) were enrolled in the study. In order to assess
      the self-esteem, social adjustment, and family functioning of these young people,
      the Culture-free Self-esteem Inventory, the Social Adjustment Scale-Self-Report,
      and the Family Assessment Device were administered. Emotional/ behavioral
      problems were assessed through the Youth Self Report and the Child Behavior
      Checklist given to both the subjects and their parents. RESULTS: No significant
      differences were found for self-esteem between the two study groups. Regarding
      social adjustment, children with cystic fibrosis reported significantly worse
      friendship and overall adjustment (P < 0.05). Moreover, no difference was found
      in the levels of family functioning between the two groups. No significant
      differences between the groups were found in emotional/ behavioral problems from
      the self-reports. On the contrary, parents of children with cystic fibrosis
      reported significantly higher levels of withdrawal/ depression, thought problems,
      and delinquent behavior (P <= 0.01) as compared to controls. CONCLUSIONS:
      Children and adolescents with cystic fibrosis appear to be a psychosocially
      vulnerable group. A biopsychosocial approach should emphasize the assessment and
      treatment of the psychosocial distress of these patients alongside multiple
      somatic treatments.

PMID- 24940356
TI  - Human variome project - current overview.

PMID- 24940355
TI  - Unravelling the spirits' message: a study of help-seeking steps and explanatory
      models among patients suffering from spirit possession in Uganda.
AB  - As in many cultures, also in Uganda spirit possession is a common idiom of
      distress associated with traumatic experiences. In the DSM-IV and -5, possession
      trance disorders can be classified as dissociative disorders. Dissociation in
      Western countries is associated with complicated, time-consuming and costly
      therapies. Patients with spirit possession in SW Uganda, however, often report
      partial or full recovery after treatment by traditional healers. The aim of this
      study is to explore how the development of symptoms concomitant help-seeking
      steps, and explanatory models (EM) eventually contributed to healing of patients
      with spirit possession in SW Uganda. Illness narratives of 119 patients with
      spirit possession referred by traditional healers were analysed using a mixed
      method approach. Treatments of two-thirds of the patients were unsuccessful when
      first seeking help in the medical sector. Their initially physical symptoms
      subsequently developed into dissociative possession symptoms. After an average of
      two help-seeking steps, patients reached a healing place where 99% of them found
      satisfactory EM and effective healing. During healing sessions, possessing agents
      were summoned to identify themselves and underlying problems were addressed.
      Often-mentioned explanations were the following: neglect of rituals and of
      responsibilities towards relatives and inheritance, the call to become a healer,
      witchcraft, grief, and land conflicts. The results demonstrate that traditional
      healing processes of spirit possession can play a role in restoring connections
      with the supra-, inter-, intra-, and extra-human worlds. It does not always seem
      necessary to address individual traumatic experiences per se, which is in line
      with other research in this field. The study leads to additional perspectives on
      treatment of trauma-related dissociation in Western countries and on developing
      effective mental health services in low -and middle-income countries. 

PMID- 24940357
TI  - Non-coding RNA based regulation of blood vessel development in zebrafish and
      relevance to humans.

PMID- 24940358
TI  - Microdeletion syndromes.

PMID- 24940359
TI  - Basic principles of prenatal screening for aneuploidies.

PMID- 24940360
TI  - Prenatal screening for Mendelian disorders in antenatal care.

PMID- 24940361
TI  - Uniparental disomy - clinical consequences due to imprinting and activation of
      recessive genes.

PMID- 24940362
TI  - Genomic packaging and epigenetic regulation of genes.

PMID- 24940363
TI  - Exome sequencing in unspecific intellectual disability and rare disorders.

PMID- 24940364
TI  - Molecular study of lysosomal storage disorders in India.

PMID- 24940365
TI  - Genomic copy number variations in glaucomatous neurodegeneration.

PMID- 24940366
TI  - Newborn screening- the roadmap for India.

PMID- 24940367
TI  - Thalassemias: can we reduce the national burden?

PMID- 24940369
TI  - Small supernumerary marker chromosomes - an update.

PMID- 24940368
TI  - Mutational landscape of gingivo-buccal oral cancer: new cancer genes and
      molecular subgroups identified.

PMID- 24940370
TI  - In search of epi-driver genes in head and neck cancer.

PMID- 24940371
TI  - Prakruti genomics and prameha-proclivity: relevance to metabolic syndrome.

PMID- 24940372
TI  - Detection and Inheritance Pattern of Copy Number Variations (CNVs) in Children
      with Multiple Congenital Anomalies.

PMID- 24940373
TI  - Clinical aspects of neuroregression: our experience on batten disease.

PMID- 24940374
TI  - Dysmorphology of inborn errors of metabolism.

PMID- 24940375
TI  - Haemophilia - diagnosis and management challenges.

PMID- 24940376
TI  - Community genetics approaches in the prevention of beta-thalassemia: towards
      achieving 'Zero beta-thalassemia' status in India.

PMID- 24940377
TI  - Pre-implantation and polar body diagnosis in cases of parental chromosomal
      translocations applying array-CGH.

PMID- 24940378
TI  - Consanguinity and perinatal medicine - the berlin perspective.

PMID- 24940379
TI  - Pharmacogenomics of cardiovascular drugs.

PMID- 24940381
TI  - G protein signaling in tumor cell growth and metastasis.

PMID- 24940380
TI  - Digital health, microfluidics, and bedside genetic testing.

PMID- 24940382
TI  - Mitochondrial donation by stem cells: potential for novel therapeutics.

PMID- 24940383
TI  - Haematopoetic stem cell transplantation at apollo group hospitals.

PMID- 24940384
TI  - Perspective of stem cell research & therapy in diabetes.

PMID- 24940385
TI  - Functional genomics of lung cancer progression reveals mechanism of metastasis
      suppressor function.

PMID- 24940387
TI  - Pituitary stalk management during the microsurgery of craniopharyngiomas.
AB  - In the present study, 203 patients that had previously undergone microsurgery for
      craniopharyngiomas (CPs) between 1992 and 2012 were analyzed retrospectively on a
      long-term follow-up basis to investigate the differences in the recurrence rate
      and endocrine function between patients with preserved and resected pituitary
      stalks. To summarize the possible outcomes of microsurgery, the 203 patients were
      divided into 2 groups: Group A that had preserved pituitary stalks and Group B
      that had undergone resections of the pituitary stalk. Tumor origins and the
      involvement of the pituitary stalk during surgery were observed. From 2010
      onwards, an ultra-electron microscope was used postoperatively to detect whether
      pituitary stalk specimens were infiltrated or invaded with tumor cells. Long-term
      follow-up observations of the patients included tumor recurrence, postoperative
      endocrine dysfunction and visual acuity and field. Among the 203 patients, 175
      patients received gross-total resection (GTR) (175/203, 86.2%), 28 patients
      underwent subtotal resection (28/203, 13.8%) and 34 patients had surgery that
      preserved the pituitary stalk (34/203, 16.7%). There was no significant
      difference in the recurrence rate between Group A (4/34, 11.8%) and the patients
      in Group B (10/123, 8.1%) who underwent GTR and also received follow-ups. Of the
      157 patients who were followed up, 91 individuals underwent endocrine evaluation
      and the outcome was divided into normal, satisfactory and poor grades. The
      results for Group A were 5, 18 and 0, respectively, while the results for Group B
      were 1, 60 and 7, respectively, which showed a statistically significant
      difference between the groups. Pituitary stalk specimens of 15 patients were
      studied postoperatively using an ultra-electron microscope and all samples showed
      tumor cells had invaded the pituitary stalk (15/15, 100%). Total resections of
      CPs with the pituitary stalk were recommended if the pituitary stalk was
      intraoperatively invaded. In cases where the pituitary stalk was not involved,
      microsurgical excisions preserving the pituitary stalk were preferred, as there
      was no significant increase in the recurrence rate and the patients experienced
      less endocrine dysfunction.

PMID- 24940386
TI  - The interplay between Campylobacter and Helicobacter species and other
      gastrointestinal microbiota of commercial broiler chickens.
AB  - BACKGROUND: Poultry represent an important source of foodborne enteropathogens,
      in particular thermophilic Campylobacter species. Many of these organisms
      colonize the intestinal tract of broiler chickens as harmless commensals, and
      therefore, often remain undetected prior to slaughter. The exact reasons for the
      lack of clinical disease are unknown, but analysis of the gastrointestinal
      microbiota of broiler chickens may improve our understanding of the microbial
      interactions with the host. METHODS: In this study, the fecal microbiota of 31
      market-age (56-day old) broiler chickens, from two different farms, was analyzed
      using high throughput sequencing. The samples were then screened for two emerging
      human pathogens, Campylobacter concisus and Helicobacter pullorum, using species
      specific PCR. RESULTS: The gastrointestinal microbiota of chickens was classified
      into four potential enterotypes, similar to that of humans, where three
      enterotypes have been identified. The results indicated that variations between
      farms may have contributed to differences in the microbiota, though each of the
      four enterotypes were found in both farms suggesting that these groupings did not
      occur by chance. In addition to the identification of Campylobacter jejuni
      subspecies doylei and the emerging species, C. concisus, C. upsaliensis and H.
      pullorum, several differences in the prevalence of human pathogens within these
      enterotypes were observed. Further analysis revealed microbial taxa with the
      potential to increase the likelihood of colonization by a number of these
      pathogens, including C. jejuni. CONCLUSION: Depletion of these taxa and the
      addition of taxa that compete with these pathogens, may form the basis of
      competitive exclusion strategies to eliminate them from the gastrointestinal
      tract of chickens.

PMID- 24940388
TI  - Luteolin inhibits SH-SY5Y cell apoptosis through suppression of the nuclear
      transcription factor-kappaB, mitogen-activated protein kinase and protein kinase
      B pathways in lipopolysaccharide-stimulated cocultured BV2 cells.
AB  - Microglial activation is one of the causative factors for neuroinflammation,
      which is associated with the pathophysiology of neurodegenerative diseases. Our
      previous study showed that the flavonoid luteolin inhibited several pro
      inflammatory enzymes and pro-inflammatory cytokines that are induced by activated
      microglia; however, its effect on signaling pathways is currently unknown. The
      present study examined the effects of luteolin on signaling pathways stimulated
      by lipopolysaccharide (LPS), including Toll-like receptor-4 (TLR-4), nuclear
      transcription factor-kappaB (NF-kappaB), mitogen-activated protein kinase (MAPK)
      family and protein kinase B (Akt) pathways in murine microglial BV2 cells. In
      addition, BV2 microglia and SH-SY5Y neuroblastoma cells were cocultured to
      observe the indirect neuroprotective effects of luteolin. Luteolin inhibited the
      LPS-stimulated expression of TLR-4. In addition, luteolin blocked LPS-induced NF
      kappaB, p38, JNK and Akt activation, but had no effect on ERK. When SH-SY5Y cells
      were cocultured with LPS-stimulated BV2 microglia, pretreatment with luteolin
      increased neuronal viability and reduced the number of apoptotic cells. These
      data suggest that luteolin has a beneficial effect on neuroinflammatory events in
      neurodegenerative diseases via suppression of the NF-kappaB, MAPK and Akt
      pathways in activated microglial cells.

PMID- 24940390
TI  - Expression of ERbeta, ERalpha and Her-2 and distribution of molecular subtypes in
      Uygur and Han patients with breast cancer.
AB  - The aim of the present study was to investigate the expression levels of estrogen
      receptor (ER) alpha and beta and human epidermal growth factor receptor-2 (Her
      2), as well as the distribution of breast cancer molecular subtypes in Uygur and
      Han breast cancer patients. Cancer tissues were collected and analyzed from 709
      breast cancer patients enrolled between January 2000 and December 2010. The
      expression levels of ERalpha, ERbeta and Her-2 were determined by
      immunohistochemistry. The differences in expression and molecular subtype
      distribution between Uygur and Han patients with breast cancer were analyzed
      using a Pearson's chi2 test. Statistically significant differences were observed
      in the expression levels of ERbeta, ERalpha and Her-2 between the Uygur and Han
      patients with breast cancer (P<0.05). The expression levels of ERbeta (++),
      ERbeta (+++) and Her-2 (+++) in Uygur patients were significantly higher, while
      the expression levels of ERalpha (+++) in Uygur patients were significantly lower
      when compared with Han patients. The percentage of luminal A type breast cancer
      in Uygur patients was significantly lower when compared with the Han patients,
      whereas the percentages of basal-like and Her-2 overexpression types were
      significantly higher than those in Han patients (P<0.05). Therefore, expression
      levels of ERbeta, ERalpha and Her-2, and molecular subtypes of breast cancer were
      significantly different between the Uygur and Han populations.

PMID- 24940389
TI  - DNA demethylation in the PTEN gene promoter induced by 5-azacytidine activates
      PTEN expression in the MG-63 human osteosarcoma cell line.
AB  - This study used the MG-63 osteosarcoma cell line to investigate the demethylation
      of the phosphate and tension homolog (PTEN) gene promoter and the change in PTEN
      gene expression levels, which are caused by the methylation inhibitor 5
      azacytidine (5-Zac), and the association between the two. Different
      concentrations of 5-Zac (0, 5 and 10 MUmol/l) were added into the MG-63 cell
      culture medium and the cells were cultured for 72 h. The following techniques
      were performed on the cells: Western blot analysis to detect the PTEN protein;
      reverse transcription-polymerase chain reaction (PCR) to detect the mRNA
      transcription levels of the PTEN gene; flow cytometry to detect the cell
      apoptotic rate; and sodium bisulfate to deal with the DNA of each group. The
      genes of the PTEN promoter and the transcription factors specificity protein 1
      (Sp1) and Myc were PCR amplified and transformed into Escherichia coli, then a
      number of clones were selected for sequencing and the methylation status of the
      amplified PTEN promoter fragment was detected. Following culture of the MG-63
      cells with 5-Zac at concentrations of 0, 5 and 10 MUmol/l for 72 h, the
      expression levels of PTEN protein in each group were gradually increased,
      presenting a concentration-dependent effect: Group 0 MUmol/l compared with groups
      5 and 10 MUmol/l, P<0.05; and group 5 MUmol/l compared with group 10 MUmol/l,
      P=0.007. The mRNA expression levels of the PTEN gene significantly increased. The
      apoptotic rates of groups 0, 5 and 10 MUmol/l were 0.69+/-0.42, 2.50+/-0.30 and
      6.59+/-0.62%, and significant differences (P<0.01) were observed between every
      two groups. The bisulfate DNA sequencing results of three groups showed that,
      following the treatment with 5-Zac, the binding of the CG site to transcription
      factors was affected by demethylation. The average rate of demethylation
      indicated a statistical difference among the three groups. In conclusion, the
      methylation inhibitor 5-Zac leads to a significant increase in the expression
      levels of the tumor suppressor gene PTEN in the MG-63 osteosarcoma cell line in
      vitro. The expression levels of mRNA and the cellular apoptotic rate were also
      increased. The elevated activation and expression levels of the PTEN gene may be
      associated with the low methylation levels of the CG site that binds to the
      transcription factors Sp1 and Myc in the PTEN gene promoter, and they promote the
      combination of the transcription factors and the gene promoter.

PMID- 24940391
TI  - Effect of neoadjuvant chemotherapy combined with hyperthermic intraperitoneal
      perfusion chemotherapy on advanced gastric cancer.
AB  - Neoadjuvant and hyperthermic intraperitoneal chemotherapies have been shown to be
      effective in the treatment of resectable advanced gastric cancer. The aim of the
      present study was to investigate the clinical efficiency and security of
      neoadjuvant chemotherapy in combination with hyperthermic intraperitoneal
      chemotherapy for the treatment of postoperative advanced gastric cancer. A total
      of 192 patients diagnosed with advanced gastric cancer were randomly divided into
      the following four groups (n=48 per group): Control, neoadjuvant chemotherapy,
      hyperthermic intraperitoneal perfusion chemotherapy and joint groups. The joint
      group received neoadjuvant chemotherapy combined with hyperthermic
      intraperitoneal perfusion chemotherapy. Complications, adverse reactions,
      recurrence rates within 2 years and the 1- and 3-year survival rates following
      surgery were observed. No significant differences were observed in the occurrence
      rates of I-II degree myelosuppression, III-IV degree myelosuppression, I-II
      degree nausea or III-IV degree nausea and vomiting among the four groups
      (P>0.05). The median progression-free survival times were 26, 31, 33 and 28
      months in the control, neoadjuvant chemotherapy, hyperthermic intraperitoneal
      perfusion chemotherapy and joint groups, respectively (P<0.001). Compared with
      the control group, the recurrence-free 2-year survival rate of the joint group
      was significantly lower (P=0.04). The difference among the median survival times
      of the four groups was statistically significant (P=0.001). The 1-year survival
      rate of the joint group was significantly higher when compared with the control
      group and the difference was statistically significant (P=0.03). However, no
      statistically significant difference was identified among the 1-year survival
      rates of the four groups (P>0.05). Compared with the control group, the 3-year
      survival rates of the other three groups were significantly higher (P<0.05).
      Therefore, the results of the present study indicated that neoadjuvant
      chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy
      for the treatment of advanced gastric cancer is well tolerated and exhibits
      improved compliance and efficiency.

PMID- 24940392
TI  - Effect of portal vein ligation on tumor growth and liver regeneration in rat
      cirrhotic liver lobes.
AB  - The aim of the present study was to investigate the effect of portal vein
      ligation (PVL) on the tumor growth rate and liver regeneration in rat cirrhotic
      liver lobes. A total of 45 male Wistar rats were randomly divided into PVL,
      hepatic tumor (HT) and HT + PVL groups (n=15 per group). Liver regeneration and
      tumor growth in ligated and non-ligated lobes were evaluated prior to and
      following PVL. In addition, serum alanine transaminase, total bilirubin levels
      and liver tissue samples were evaluated. The results indicated that PVL induced
      apparent hypertrophy in normal and HT rats. However, the ratio of non-ligated
      lobes to total liver weight or body weight in the HT + PVL group was
      significantly lower when compared with the PVL group (P<0.05). Compared with the
      HT group, the tumor growth rate in the ligated lobes of the HT + PVL group
      significantly increased (P<0.05). However, tumor growth in the non-ligated lobes
      exhibited no statistically significant difference between the HT and HT + PVL
      groups. In addition, Knodell scores indicated that fibrosis was more apparent in
      the non-ligated lobes of the HT + PVL group when compared with the HT group
      (P<0.05). Therefore, tumor growth was accelerated in ligated lobes following PVL,
      but not in non-ligated lobes. PVL also induced liver regeneration in cirrhotic
      liver lobes with lower efficiency than that in the non-cirrhotic lobes. However,
      hypertrophy in the contralateral cirrhotic lobes appeared to be non-functional.

PMID- 24940393
TI  - Biomechanical analysis of cervical myelopathy due to ossification of the
      posterior longitudinal ligament: Effects of posterior decompression and kyphosis
      following decompression.
AB  - Cervical ossification of the posterior longitudinal ligament (OPLL) results in
      myelopathy. Conservative treatment is usually ineffective, thus, surgical
      treatment is required. One of the reasons for the poor surgical outcome following
      laminoplasty for cervical OPLL is kyphosis. In the present study, a 3-dimensional
      finite element method (3D-FEM) was used to analyze the stress distribution in
      preoperative, posterior decompression and kyphosis models of OPLL. The 3D-FEM
      spinal cord model established in this study consisted of gray and white matter,
      as well as pia mater. For the preoperative model, 30% anterior static compression
      was applied to OPLL. For the posterior decompression model, the lamina was
      shifted backwards and for the kyphosis model, the spinal cord was studied at 10,
      20, 30, 40 and 50 degrees  kyphosis. In the preoperative model, high stress
      distributions were observed in the spinal cord. In the posterior decompression
      model, stresses were lower than those observed in the preoperative model. In the
      kyphosis model, an increase in the angle of kyphosis resulted in augmented stress
      on the spinal cord. Therefore, the results of the present study indicated that
      posterior decompression was effective, but stress distribution increased with the
      progression of kyphosis. In cases where kyphosis progresses following surgery,
      detailed follow-ups are required in case the symptoms worsen.

PMID- 24940395
TI  - A retrospective study of cytomegalovirus pneumonia in renal transplant patients.
AB  - The aim of the present study was to investigate an optimal prophylaxis of
      cytomegalovirus (CMV) pneumonia in renal transplant recipients. A total of 83
      kidney transplant recipients who had been diagnosed with CMV pneumonia between
      January 2008 and December 2011 were enrolled in the study. Patients were assigned
      to a standard or improved group based on the prophylaxis administered. The
      retrospective study was undertaken to compare the incidence of CMV pneumonia,
      cure rate or recovery rate and mortality between the two groups. The results
      indicated that a longer duration of prophylaxis with oral ganciclovir effectively
      reduced the risk of CMV pneumonia in kidney transplant recipients. Treatments,
      including early withdrawal of immunosuppressants, regular use of
      glucocorticosteroids and careful supportive therapy, were beneficial in
      controlling CMV pneumonia. Furthermore, antibody induction therapy may not
      increase the risk of CMV pneumonia in kidney recipients administered proper
      prophylaxis [3-month course of oral ganciclovir and trimethoprim-sulfamethoxazole
      (SMZ-TMP)]. Therefore, the present study demonstrated that a longer duration of
      prophylaxis with oral ganciclovir, withdrawal of immunosuppressants and regular
      use of glucocorticosteroids may be improved treatments for CMV pneumonia.

PMID- 24940394
TI  - Efficacy of folic acid supplementation on endothelial function and plasma
      homocysteine concentration in coronary artery disease: A meta-analysis of
      randomized controlled trials.
AB  - The aim of the present study was to conduct an updated meta-analysis of relevant
      randomized controlled trials (RCTs) in order to estimate the effect of folic acid
      supplementation on endothelial function and the concentration of plasma
      homocysteine in patients with coronary artery disease (CAD). An extensive search
      of PubMed was conducted to identify RCTs that compared folic acid with placebo
      therapy. The mean difference (MD) and 95% confidence interval (CI) were used as a
      measure of the correlation between folic acid supplementation and endothelial
      function/plasma homocysteine concentration. Of the 377 patients included in this
      analysis, 191 patients underwent folic acid supplementation and 186 individuals
      underwent placebo treatment. Compared with the use of a placebo, folic acid
      supplementation alone exhibited significant efficacy on increasing flow-mediated
      dilation (FMD; MD, 57.72 MUm; 95% CI, 50.14-65.31; P<0.05) and lowering the
      concentration of plasma homocysteine (MD, -3.66 MUmol/l; 95% CI, -5.44--1.87;
      P<0.05; I2, 87%). There was no significant change in the response to end
      diastolic diameter, glyceryl-trinitrate diameter, heart rate, baseline and peak
      hyperemic flow and systolic and diastolic blood pressure between the folic acid
      and placebo groups (P>0.05). Therefore, the meta-analysis indicated that 5 mg
      folic acid daily supplementation for >4 weeks significantly improved FMD and
      lowered the concentration of plasma homocysteine in patients with CAD. However,
      more RCTs are required in order to confirm these observations.

PMID- 24940396
TI  - Icariin attenuates angiotensin II-induced hypertrophy and apoptosis in H9c2
      cardiomyocytes by inhibiting reactive oxygen species-dependent JNK and p38
      pathways.
AB  - Icariin, the major active component isolated from plants of the Epimedium family,
      has been reported to have potential protective effects on the cardiovascular
      system. However, it is not known whether icariin has a direct effect on
      angiotensin II (Ang II)-induced cardiomyocyte enlargement and apoptosis. In the
      present study, embryonic rat heart-derived H9c2 cells were stimulated by Ang II,
      with or without icariin administration. Icariin treatment was found to attenuate
      the Ang II-induced increase in mRNA expression levels of hypertrophic markers,
      including atrial natriuretic peptide and B-type natriuretic peptide, in a
      concentration-dependent manner. The cell surface area of Ang II-treated H9c2
      cells also decreased with icariin administration. Furthermore, icariin repressed
      Ang II-induced cell apoptosis and protein expression levels of Bax and cleaved
      caspase 3, while the expression of Bcl-2 was increased by icariin. In addition,
      2',7'-dichlorofluorescein diacetate incubation revealed that icariin inhibited
      the production of intracellular reactive oxygen species (ROS), which were
      stimulated by Ang II. Phosphorylation of c-Jun N-terminal kinase (JNK) and p38 in
      Ang II-treated H9c2 cells was blocked by icariin. Therefore, the results of the
      present study indicated that icariin protected H9c2 cardiomyocytes from Ang II
      induced hypertrophy and apoptosis by inhibiting the ROS-dependent JNK and p38
      pathways.

PMID- 24940397
TI  - Varying levels of 6-keto-prostaglandin F1alpha and thromboxane B2 in serum and
      endothelialization and hyperplasia in small-diameter grafts seeded with CD34+
      bone marrow cells in canines.
AB  - The aim of the present study was to investigate the serum levels of 6-keto
      prostaglandin (PG)F1alpha and thromboxane (TX)B2, as well as the
      endothelialization and hyperplasia of polytetrafluoroethylene (PTFE) and Dacron
      prostheses seeded with CD34+ cells in medium-term observation. A total of 24
      crossbred dogs were randomly distributed into PTFE or Dacron groups. CD34+ cells
      were isolated from bone marrow aspirate and collected using an immunomagnetic
      bead-based system. The PTFE or Dacron prostheses were implanted into the
      abdominal aortic artery and inferior vena cava of the dogs. In each group, 8 dogs
      were implanted with prostheses that had been seeded with CD34+ cells, while 4
      dogs were implanted with prostheses that had been seeded with autogenous blood as
      a control. Serum concentrations of 6-keto-PGF1alpha and TXB2 were determined at
      days 0, 10, 30 and 60 following surgery. The grafts were removed and examined at
      days 10, 30, 60 and 100 following surgery. Finally, CD34 factor staining was used
      to identify endothelial cells, while light and electron microscopy were applied
      to examine endothelialization and patency. The results revealed that confluent
      endothelial cells appeared on the neointima of prostheses seeded with CD34+ cells
      at day 30 following surgery. In the control groups compared with the experimental
      groups, there were fewer endothelial cells and the neointima was significantly
      thicker in the arterial (PTFE, 174+/-1.41 vs. 117+/-2.83 MUm, respectively;
      P=0.001; Dacron, 187.5+/-3.5 vs. 100+/-1.41 MUm, respectively; P<0.001) and
      venous (PTFE, 230.5+/-6.36 vs. 135+/-5.66 MUm, respectively; P=0.001; Dacron,
      249+/-2.83 vs. 121.5+/-3.54 MUm, respectively; P<0.001) prostheses. In the
      experimental groups, intimal hyperplasia in the venous prostheses (PTFE, 135+/
      5.66 MUm; Dacron, 121.5+/-3.54 MUm) was more severe compared with that in the
      arterial prostheses (PTFE, 117+/-2.83 MUm; Dacron, 100+/-1.41 MUm) at day 60.
      Compared with the 6-keto-PGF1alpha concentrations in the experimental groups,
      those in the control groups were significantly lower on day 10 (PTFE, 135+/-6.01
      vs. 80.5+/-4.35 pg/l, respectively; P=0.001; Dacron, 145+/-6.54 vs. 81.2+/-5.10
      pg/l, respectively; P<0.001) and were then maintained at a lower level. By
      contrast, the TXB2 concentration, following marked increases on day 10 in the
      experimental and control groups (PTFE, 635+/-32.8 vs. 1,256+/-63.5 pg/l,
      respectively; P<0.001; Dacron, 652+/-30.9 vs. 1,136+/-53.2 pg/l, respectively;
      P=0.001), remained at a high level in the control groups. Therefore, the results
      of the present study indicate that it is possible to achieve rapid
      endothelialization in PTFE or Dacron prostheses by implanting CD34+ cells.
      Endothelialization inhibited the reduction in the concentration of 6-keto
      PGF1alpha and the increase in the concentration of TXB2. In addition,
      endothelialization inhibited excessive intimal hyperplasia and thrombosis. Thus,
      CD34+ cell seeding provides a theoretical basis for the clinical application of
      artificial vessel endothelialization.

PMID- 24940399
TI  - The expression of renal Epstein-Barr virus markers in patients with lupus
      nephritis.
AB  - The aim of this study was to investigate the role of renal Epstein-Barr virus
      (EBV) infection in the pathogenesis of lupus nephritis (LN). A total of 58 renal
      tissue samples from patients with LN, seven normal renal tissue samples from
      patients with non-glomerular hematuria and 37 renal tissue samples from patients
      with minimal change nephropathy were collected. The expression of EBV-latent
      membrane protein-1 (EBV-LMP1) and EBV-encoded RNA 1 (EBER-1) in the renal tissue
      was examined by immunohistochemistry (IHC) and in situ hybridization (ISH),
      respectively. The sera levels of anti-nuclear antibody as well as antibodies to
      extractable nuclear antigen in patients with LN were also measured. An
      equivalence test showed that the results from the IHC and the ISH analyses had
      strong agreement. The positive rates of renal EBER-1 and EBV-LMP1 in the LN
      patients were significantly higher than those of the normal and minimal change
      nephropathy patients (P<0.001), while no significant difference was identified
      between those of the normal and minimal change nephropathy groups (P>0.05). The
      positive rates of EBV-LMP1 and EBER-1 in the renal tissues of patients with LN
      were not determined to be significantly different between the relapse
      (immunosuppressant-treated) and initial onset (non-treated) patients, between the
      patients with and without concurrent infection, and among the patients with
      different age ranges (P>0.05). The proportion of LN patients positive for anti-Sm
      antibody was significantly higher in the renal EBV-positive group than in the EBV
      negative group (P<0.05), while the proportions of LN patients positive for the
      other autoantibodies that were examined were not identified to be significantly
      different between these two groups (P>0.05). The present study shows that renal
      EBV infection may contribute to the pathogenesis of LN by inducing anti-Sm
      antibody production.

PMID- 24940398
TI  - Renal neutrophil gelatinase-associated lipocalin and kidney injury molecule-1
      expression in children with acute kidney injury and Henoch-Schonlein purpura
      nephritis.
AB  - The aim of this study was to investigate the expression of neutrophil gelatinase
      associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the serum,
      urine and renal tissues of children with acute kidney injury (AKI) and Henoch
      Schonlein purpura nephritis (A-on-C). A prospective single-center evaluation of
      the serum, urine and renal NGAL and KIM-1 levels was performed in a cohort of
      children. Blood and 5-ml urine samples were collected from each patient for the
      analysis of NGAL and KIM-1 levels using an ELISA. In addition, the expression of
      NGAL and KIM-1 in the kidney was examined using immunohistochemistry in patients
      with A-on-C and HSPN. The expression of serum cystatin C, beta2-macroglobulin and
      serum creatinine (SCr), as well as urinary beta2-MG and SCr, in the patients with
      A-on-C was significantly higher than that of HSPN patients, and the expression of
      NGAL and KIM-1 in the serum and urine in the A-on-C patients was also
      significantly higher than that of HSPN patients. However, there were no
      significant differences in the urine protein levels between the two groups. NGAL
      and KIM-1 were expressed in renal tubular epithelial cells, and the expression of
      NGAL and KIM-1 in the A-on-C patients was significantly higher than that in HSPN
      patients. In addition, the urine NGAL and KIM-1 levels were negatively correlated
      with glomerular filtration rate, but there was no significant correlation between
      the urine NGAL/KIM-1 and urine protein levels. The changes in serum and urine
      NGAL and KIM-1 levels may be applied to the diagnosis of A-on-C.

PMID- 24940400
TI  - Glycyrrhizin improves p75NTR-associated sciatic nerve regeneration in a BALB/c
      mouse model.
AB  - Glycyrrhizin has a role in immune regulation in the central nervous system, but
      its impact on sciatic nerve injury had not previously been reported. In this
      study, a BALB/c mouse model of sciatic nerve injury was used to explore the role
      of glycyrrhizin in sciatic nerve repair and its underlying mechanism.
      Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and
      high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression
      at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control
      (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve
      injury, and simultaneously improved the action potential amplitude and motor
      nerve conductive velocity. Combined Marsland, Glees and Erikson's silver stain
      and Luxol fast blue staining results indicated that high- and mid-dose
      glycyrrhizin promoted improved sciatic nerve myelination compared with the low
      dose or control groups eight weeks after injury. Immunofluorescence staining
      demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on
      local hypertrophic scar and inflammatory responses in the mouse model. In
      conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional
      repair, in which doses of 10 and 20 mg/kg per day are more effective than lower
      doses, and such regeneration is associated with the downregulation of p75NTR.

PMID- 24940401
TI  - Material-induced chondrogenic differentiation of mesenchymal stem cells is
      material-dependent.
AB  - Certain materials may mimic natural cartilage to provide an amenable cellular
      microenvironment for the chondrogenic differentiation of mesenchymal stem cells.
      The chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs)
      has been demonstrated to be induced by collagen-based hydrogels in vivo, but
      whether the induction is material-driven or self-differentiation has not been
      elucidated. In the present study, BMSCs were encapsulated in porous materials,
      namely, a biphasic calcium phosphate ceramic (BCP), silk fibroin protein matrix
      (SFP) and collagen sponge (CS), to further study the chondrogenic effects of
      various materials. Diffusion chambers that allow the body fluid to permeate and
      deter the host cells from invasion were also loaded with the cell-scaffold
      constructs. Chambers containing the scaffold-BMSC composites were implanted
      subcutaneously in the dorsa of rabbits. The specimens in the chamber were
      harvested for histological and immunohistochemical analyses eight weeks after
      implantation. The results showed that no chondrogenic differentiation of the
      BMSCs occurred when the BMSCs were encapsulated in BCP, SFP and CS, indicating
      that chondrogenesis induced by materials is material-dependent and that these
      particular porous materials are not suitable for inducing chondrogenesis.
      However, the diffusion chamber was effective in preventing host immune rejection,
      host cell invasion and vascular invasion. The results are likely to serve as a
      valuable clinical reference when selecting an appropriate scaffold for cartilage
      repair.

PMID- 24940402
TI  - Integration of partial least squares and Monte Carlo gene expression analysis in
      coronary artery disease.
AB  - Coronary artery disease (CAD) is the most common type of cardiovascular disease
      and leading cause of mortality worldwide. Microarray technology for gene
      expression analysis has facilitated the identification of the molecular mechanism
      that underlies the pathogenesis of CAD. Previous studies have primarily used
      variance or regression analysis, without considering array specific factors.
      Thus, the aim of the present study was to investigate the mechanism of CAD using
      partial least squares (PLS)-based analysis, which was integrated with the Monte
      Carlo technique. Microarray analysis was performed with a data set of 110 CAD
      patients and 111 controls obtained from the Gene Expression Omnibus database. A
      total of 390 dysregulated genes were acquired. Significantly increased
      representations of dysregulated genes in Gene Ontology items, including
      transforming growth factor beta-activated receptor activity and acyl-CoA oxidase
      activity, were identified. Network analysis revealed three hub genes with a
      degree of >10, including ESR1, ITGA4 and ARRB2. The results of the present study
      provide novel information on the gene expression signatures of CAD patients and
      offer further theoretical support for future therapeutic study.

PMID- 24940403
TI  - Dual-source CT coronary angiographic evaluation of coronary artery fistulas.
AB  - The aim of the present study was to retrospectively evaluate the incidence and
      morphological features of coronary artery fistulas (CAFs) detected by dual-source
      computed tomography coronary angiography (DS-CTCA). Between January 2011 and
      January 2013, 19,584 consecutive patients that had undergone electrocardiogram
      triggering DS-CTCA were retrospectively reviewed. Image reconstructions were
      performed and image quality was evaluated. The medical information of the
      patients with CAF was reviewed from the medical records. Among the 19,584
      patients, 66 patients were diagnosed with CAFs by CTCA, including 60 patients
      with coronary pulmonary artery fistulas (CPAFs) and six with coronary left
      ventricular fistulas. Therefore, the incidence of CAFs was 0.34%. Image quality
      was considered to be excellent in 61 patients and moderate in five cases. CPAFs
      were identified as small and tortuous vessels in 24 patients and dilated vessels
      close to the surface of the pulmonary artery (PA) in 36 patients. The coronary
      left ventricular fistulas were identified as dilated vessels that were draining
      into the posterior wall of the left ventricle. Among the 66 patients, 54 patients
      had one traceable fistula and the remaining 12 patients were shown to have two
      fistula vessels. The average diameter of the detected fistulas, measured with
      CTCA, was 3.1+/-1.9 mm. A high-density flow jet of contrast agent shunting from
      the fistula into the low density PA was observed in 46 patients with CPAF. The
      results indicate that DS-CTCA is a reliable noninvasive tool that allows the
      accurate delineation of CAFs.

PMID- 24940405
TI  - Recurrence of histiocytic necrotizing lymphadenitis: A case report and literature
      review.
AB  - Histiocytic necrotizing lymphadenitis (HNL) is a unique form of self-limiting
      lymphadenitis with an unknown cause. The majority of cases resolve within several
      months and the disease has a low recurrence rate of 3-4%. In the present study, a
      prolonged recurrent case of HNL was reported. A 44-year-old female developed
      recurrent HNL with generalized lymphadenopathy 14 years after the original
      episode.

PMID- 24940404
TI  - Differential plasma proteome analysis in patients with high-altitude pulmonary
      edema at the acute and recovery phases.
AB  - This study aimed to investigate the differential expression of plasma proteins in
      patients suffering from high-altitude pulmonary edema (HAPE) at different phases.
      A complete proteomic analysis was performed using two-dimensional gel
      electrophoresis followed by mass spectrometry in three patients with HAPE at the
      acute stage and recovery phase. Comparisons between the expression patterns of
      the patients with HAPE at the two different phases led to the identification of
      eight protein spots with a >1.5-fold difference in expression between the acute
      and recovery phases. These differentially expressed proteins were
      apolipoproteins, serum amyloid P component, complement components and others.
      Apolipoprotein A-I (Apo A-I), serum amyloid P component and fibrinogen were
      overexpressed in the patients with HAPE in the acute stage compared with their
      expression levels in the recovery phase. However, Apo A-IV and antithrombin-III
      were overexpressed in the patients with HAPE in the recovery phase compared with
      their expression levels in the acute stage. The results indicate that the
      differential plasma proteome in patients with HAPE may be associated with the
      occurrence of HAPE, and the expression changes of Apo A-I and A-IV may offer
      further understanding of HAPE to aid its prognosis, diagnosis and treatment.

PMID- 24940407
TI  - Correlation between the severity of coronary artery lesions and levels of
      estrogen, hs-CRP and MMP-9.
AB  - The aim of this study was to investigate the correlation between the severity of
      coronary artery lesions in patients with acute coronary syndromes (ACS) and
      levels of estrogen, high-sensitivity C-reactive protein (hs-CRP) and matrix
      metalloproteinase-9 (MMP-9). A total of 65 patients with ACS, 33 patients with
      stable angina pectoris (SAP) and 36 healthy controls were randomly enrolled.
      Patients with ACS were subdivided into two groups: Acute myocardial infarction
      (AMI; n=30) and unstable angina pectoris (UAP; n=35). Serum levels of estrogen,
      hs-CRP and MMP-9 were detected in the four groups of subjects. Serum estrogen
      levels in patients with AMI, UAP and SAP were significantly lower than those in
      the control group (P<0.05). Estrogen levels were also significantly different
      among the AMI, UAP and SAP groups (P<0.05), with a progressive increase across
      the three respective groups. Compared with healthy subjects, patients with AMI
      had the highest levels of hs-CRP and MMP-9, followed in descending order by those
      with UAP and SAP (P<0.05). Levels of hs-CRP and MMP-9 were also significantly
      different among the AMI, UAP and SAP groups (P<0.05). Serum estrogen levels were
      negatively correlated with hs-CRP and MMP-9 levels (r=-0.6634 and -0.6878,
      respectively; both P<0.05). hs-CRP and MMP-9 levels correlated positively
      (r=0.7208, P<0.05). The number of stenosed coronary vessels was negatively
      correlated with estrogen levels (r=-0.6467, P<0.05), and positively correlated
      with hs-CRP and MMP-9 levels (r=0.6519 and 0.6835, respectively; both P<0.05). In
      conclusion, serum estrogen, hs-CRP and MMP-9 levels were significantly correlated
      with the severity of coronary artery lesions. There was also a significant
      correlation between serum estrogen, hs-CRP and MMP-9 levels. These data indicate
      that serum estrogen, hs-CRP and MMP-9 have the potential to be used as biomarkers
      for evaluating the severity of coronary artery lesions and the stability of
      coronary artery plaques.

PMID- 24940406
TI  - PinX1-siRNA/mPEG-PEI-SPION combined with doxorubicin enhances the inhibition of
      glioma growth.
AB  - Resistance to chemotherapy and the side effects of anticancer drugs are the major
      obstacles for glioma treatment. The aim of the present study was to develop a
      novel approach for the treatment of gliomas that improved the therapeutic effect;
      the anticancer drug, doxorubicin (DOX), was combined with short interfering
      (si)RNA and monomethoxy polyethylene glycol polyethylenimine superparamagnetic
      iron oxide nanoparticle (mPEG-PEI-SPION), a magnetic resonance imaging (MRI)
      visible nanoparticle. Specific siRNA molecules, delivered by mPEG-PEI-SPION, were
      employed to knockdown the PIN2-interacting protein 1 (PinX1) gene in C6 glioma
      cells. PinX1 is a nucleolar protein associated with telomere and telomerase. C6
      cells were treated with DOX and/or PinX1-siRNA. The results of the transfection
      experiments revealed that siRNA/mPEG-PEI-SPION was transfected into C6 cells with
      high efficiency. PinX1-siRNA was unable to inhibit C6 cells, while in the PinX1
      siRNA + DOX group, the same dose of DOX caused an increased loss of cell
      viability. Therefore, mPEG-PEI-SPION was shown to be viable for siRNA delivery
      into C6 cells and coadministration of DOX with PinX1-siRNA may be a potential
      therapeutic method for inhibiting gliomas.

PMID- 24940408
TI  - Meta-analysis of the therapeutic effects of antibiotic versus appendicectomy for
      the treatment of acute appendicitis.
AB  - Appendicectomy has been the gold standard treatment of acute appendicitis for
      more than a century, while nonoperative therapies, including antibiotics, have
      acquired increased interest in recent years. The present meta-analysis aimed to
      compare the therapeutic effects of antibiotics versus appendicectomy for the
      treatment of acute appendicitis. Medline, Embase and The Cochrane Library
      databases were searched. Prospective randomized controlled trials that compared
      antibiotic treatment with surgery were included. The outcomes evaluated included
      the time of hospital stay, complications and time to work. There were no
      statistically significant differences between the antibiotic and appendicectomy
      groups with regard to the time of hospital stay and complications. However, the
      time to work was significantly longer in the appendicectomy group when compared
      with the antibiotic group. In addition, the therapeutic effects of antibiotics
      and appendicectomy were comparable for the treatment of acute appendicitis.

PMID- 24940409
TI  - Total flavonoids from Plumula Nelumbinis suppress angiotensin II-induced
      fractalkine production by inhibiting the ROS/NF-kappaB pathway in human umbilical
      vein endothelial cells.
AB  - Angiotensin II (Ang II) is a neuroendocrine factor that promotes hypertension and
      has been implicated in vascular inflammation through the induction of reactive
      oxygen species (ROS) and proinflammatory genes in endothelial cells. However,
      relatively little attention has been paid to the effect of Ang II on fractalkine
      (FKN), an important chemokine involved in endothelial dysfunction. In the study,
      we aimed to investigate the protective role of total flavonoids from Plumula
      Nelumbinis (TFPN), the main component extracted from Semen Nelumbinis, in Ang II
      induced oxidative stress injury in human umbilical vein endothelial cells
      (HUVECs). Furthermore, we studied whether TFPN could attenuate the Ang II-induced
      generation of ROS and the activation of nuclear factor-kappaB (NF-kappaB);
      whether these Ang II-induced effects were inhibited by apocynin (a nicotinamide
      adenine dinucleotide phosphate oxidase inhibitor) and pyrrolidine dithiocarbamate
      (an NF-kappaB inhibitor). In the present study, it was observed that total
      flavonoids from Plumula Nelumbinis (TFPN), the main component extracted from
      Semen Nelumbinis, concentration-dependently inhibited the FKN production induced
      by Ang II in human umbilical vein endothelial cells (HUVECs). Furthermore, TFPN
      attenuated the Ang II-induced generation of ROS and the activation of nuclear
      factor-kappaB (NF-kappaB); these Ang II-induced effects were also inhibited by
      apocynin (a nicotinamide adenine dinucleotide phosphate oxidase inhibitor) and
      pyrrolidine dithiocarbamate (an NF-kappaB inhibitor). In conclusion, the findings
      of the present study indicate that TFPN attenuate Ang II-induced upregulation of
      FKN by inhibiting the ROS/NF-kappaB pathway in HUVECs and thus have a suppressive
      effect on vascular inflammation.

PMID- 24940410
TI  - Preventive effects of basic fibroblast growth factor on vascular restenosis after
      balloon angioplasty.
AB  - The aim of the present study was to investigate whether chronic administration of
      basic fibroblast growth factor (bFGF) following angioplasty in a dog model of
      atherosclerotic iliac stenosis may restore endothelium function and prevent
      restenosis (RS). In total, 40 dogs with atherosclerotic stenosis of the right
      iliac arteries were used in the study. A total of 20 dogs underwent histological
      examination of the lumen areas prior to (n=10) and immediately following
      angioplasty (n=10). Intravenous bFGF was administered to 10 dogs (bFGF group) and
      an additional 10 dogs received vehicle injection (control group). Animals in the
      two groups were sacrificed 42 days following surgery for in vitro analysis of
      vascular reactivity and morphometric assessment of the histological cross
      sectional areas. The bFGF group exhibited significantly greater maximal
      endothelium-dependent acetylcholine-induced relaxation (Emax, 43+/-9%) when
      compared with the control group (Emax, 8+/-6%; P<0.05). In addition, the maximal
      endothelium-independent response of the bFGF group to sodium nitroprusside (Emax,
      90+/-2%) was greater than that of the control group (Emax, 60+/-2%; P<0.05). Six
      weeks following angioplasty, the lumen area in the bFGF group (2.01+/-0.78 mm2)
      was greater compared with the control group (1.0+/-0.10%). The lumen area
      decreased by 58% between immediately after angioplasty and the control group six
      weeks following angioplasty. Therefore, the results of the present study
      indicated that administration of bFGF may not only restore endothelium-dependent
      and -independent relaxation, but also prevent RS in dogs that have undergone
      angioplasty.

PMID- 24940411
TI  - Effects of ethyl pyruvate on cardiac function recovery and apoptosis reduction
      after global cold ischemia and reperfusion.
AB  - The present study used an in vitro model of cold cardioplegia in isolated working
      rat hearts to evaluate the possible role of ethyl pyruvate (EP) in promoting
      cardiac function and preventing apoptosis. Two groups of rats were evaluated; the
      EP (2 mM EP; n=8) and control (n=8) groups. Isolated rat hearts were perfused
      with Krebs-Henseleit buffer (KHB) for 30 min, arrested with cardioplegic solution
      and stored for 4 h in B21 solution at 4 degrees C. The hearts were reperfused
      with KHB for 45 min. EP was added to the cardioplegic and storage solutions and
      also to KHB for reperfusion. Cardiac parameters of the heart rate, including left
      ventricular systolic pressure, left ventricular end-diastolic pressure, left
      ventricular developed pressure and maximal rise rate of the left ventricular
      pressure, were monitored. In addition, coronary flow, adenosine triphosphate
      (ATP) levels and malondialdehyde (MDA) content were recorded and apoptotic cell
      determination was detected. The functional parameters in the EP group were
      significantly higher compared with those in the control group during the
      reperfusion period (P<0.05). In addition, ATP levels were higher in the EP group
      than in the control group and the content of MDA was lower in the EP group than
      in the control group. A concentration of 2 mM EP significantly reduced the number
      of apoptotic cells in the EP group compared with that of the control group
      (P<0.05). Therefore, EP significantly preserved cardiac function, enhanced tissue
      ATP levels, attenuated myocardial oxidative injury and markedly reduced apoptosis
      following myocardial ischemia in an in vitro model of 4 h of cold cardioplegia
      and reperfusion.

PMID- 24940412
TI  - A comparative study of the efficacy and safety of radiofrequency ablation and
      botulinum toxin A in treating masseteric hypertrophy.
AB  - The aim of the present study was to evaluate the effects of two treatments for
      masseteric hypertrophy. In total, 24 patients with masseteric hypertrophy were
      enrolled in this study. Patients were randomly divided into two groups: 12
      individuals were treated with radiofrequency (RF) ablation and 12 patients
      received an injection of botulinum toxin A. The thickness of the masseter muscle
      under tension was measured using ultrasound and clinical photographs were
      captured prior to treatment and at 6 and 12 months following treatment.
      Complications were observed during 12-month follow-up. In the group injected with
      botulinum toxin A, masseteric muscle thickness decreased to the lowest point 6
      months after the injections but increased until 12 months after injection.
      However, in the group treated with RF ablation, muscle thickness decreased
      steadily over the 12 months following surgery. Therefore, the results of the
      present study indicated that the effect of RF ablation on the thickness of the
      masseter muscle may be much larger than that obtained following injection with
      botulinum toxin A.

PMID- 24940413
TI  - Effect of cilostazol pretreatment on the PARP/AIF-mediated apoptotic pathway in
      rat cerebral ischemia-reperfusion models.
AB  - The aim of this study was to observe the expression of poly ADP-ribose polymerase
      (PARP) and apoptosis-inducing factor (AIF) in the CA1 region of the hippocampus
      and to explore whether cilostazol pretreatment exerts a protective effect on the
      brain through the PARP/AIF-mediated pathway in a rat model of cerebral ischemia
      reperfusion. Rats were randomly divided into three groups: Sham-surgery, ischemia
      reperfusion and cilostazol (n=45 rats/group). Rat models of middle cerebral
      artery occlusion were prepared using a thread occlusion method. Rats in the
      cilostazol group were administered 30 mg/kg intragastric cilostazol 6 and 2 h
      before brain ischemia, respectively. Following reperfusion, samples were
      collected at different time-points (6, 24 and 72 h) and each group was further
      subdivided into three subgroups (n=15 rats/subgroup). Apoptosis was measured
      using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling
      method. The protein expression levels of AIF and PARP were detected using western
      blot analysis and the expression levels of AIF mRNA were determined using the
      reverse transcription-polymerase chain reaction. AIF nuclear translocation
      occurred following local cerebral ischemia-reperfusion injury. Apoptosis, levels
      of AIF and PARP protein expression and levels of AIF mRNA expression were
      significantly increased in the ischemia-reperfusion group compared with the sham
      surgery group (P<0.05). However, apoptosis and the expression levels of AIF
      protein, PARP protein and AIF mRNA at different time-points were significantly
      decreased in the cilostazol group compared with the ischemia-reperfusion group
      (P<0.05). In conclusion, cilostazol has a protective effect on rat cerebral
      ischemia-reperfusion injury, and acts by inhibiting nerve cell apoptosis by
      preventing the excessive activation of PARP and AIF nuclear translocation.

PMID- 24940414
TI  - Plasma visfatin levels and mRNA expression of visfatin in peripheral blood
      mononuclear cells and peripheral blood monocyte-derived macrophages from normal
      weight females with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common reproductive endocrinology disease,
      however, an explicit etiology is not known. Insulin resistance (IR) appears to be
      central to the pathogenesis of PCOS and inflammation may be significant in the
      pathogenesis of IR in PCOS. The aims of the present study were to investigate the
      plasma visfatin level and the gene expression of visfatin in peripheral blood
      mononuclear cells (PBMCs) and peripheral blood monocyte-derived macrophages
      (PBMMs) from PCOS patients, in addition to investigating the association between
      PCOS and IR. A total of 21 PCOS patients and 21 control subjects were enrolled in
      the study; the homeostasis model assessment of insulin resistance (HOMA-IR) was
      considered to be a stratified method for establishing the subgroups. Fasting
      blood samples were collected and the levels of sex hormones, insulin, glucose,
      blood lipids and visfatin were measured. In addition, visfatin gene expression
      levels in PBMCs and PBMMs were assessed using quantitative polymerase chain
      reaction. The plasma visfatin and gene expression levels of visfatin in PBMCs and
      PBMMs were not observed to increase in the normal weight PCOS and normal weight
      IR patients. Furthermore, plasma visfatin levels did not correlate with the
      normal weight PCOS patients or the normal weight IR patients per se. Further
      investigation into the role of visfatin in the pathogenesis of PCOS or IR should
      examine macrophages in the tissues, rather than macrophages in the peripheral
      blood.

PMID- 24940415
TI  - Vacuum-assisted closure increases ICAM-1, MIF, VEGF and collagen I expression in
      wound therapy.
AB  - Severe traumatic wounds are challenging to manage during surgery. The
      introduction of vacuum-assisted closure (VAC) is a breakthrough in wound
      management. The aim of the present study was to investigate the effect of VAC on
      cytokines in wounds during the management of severe traumatic wounds following
      initial debridement. VAC and conventional wound care (CWC) were independently
      applied to severe traumatic wounds on pigs. The expression levels of
      intercellular adhesion molecule-1 (ICAM-1), migration inhibitory factor (MIF),
      vascular endothelial growth factor (VEGF), basic fibroblast growth factor,
      collagen I and human fibroblast collagenase 1 were detected by quantitative
      polymerase chain reaction and western blotting. VAC significantly increased the
      expression of ICAM-1, MIF, VEGF and collagen I compared with that induced by CWC
      at the protein and mRNA levels. Therefore, the results of the present study
      indicate that VAC therapy is an effective method for treating severe traumatic
      wounds, as it increases the expression of cytokines in wounds. VAC significantly
      increases the expression of ICAM-1, MIF, VEGF and collagen I to manage severe
      traumatic wounds.

PMID- 24940416
TI  - Effect of sodium valproate on the sleep structures of epileptic patients.
AB  - The aims of the present study were to investigate the effect of sodium valproate
      (VPA) on the sleep structures of epileptic patients and the correlation of these
      effects with patient weight gain. A total of 60 epileptic patients were divided
      into three groups: E-AED I (VPA administration for a duration of <3 months), E
      AED II (VPA administration for a duration of >3 months) and ECO (without VPA)
      groups, for polysomnography monitoring. When the E-AED II group was compared with
      the E-AED I and ECO groups, non-rapid eye movement sleep phase 1 was
      significantly prolonged (92.10+/-48.24, 29.50+/-10.61 and 23.94+/-13.27 min,
      respectively; P<0.01), rapid eye movement sleep was significantly shortened
      (70.82+/-17.69, 116.99+/-12.90 and 126.19+/-35.01 min, respectively; P<0.01),
      sleep efficiency was significantly reduced (89.39+/-2.55, 91.98+/-2.53 and
      91.96+/-3.14%, respectively; P<0.01), the number of times of that the patients
      awoke was significantly increased (7.25+/-2.86, 2.55+/-1.42 and 2.40+/-1.39,
      respectively; P<0.01) and the number of REM phases throughout the night was
      significantly reduced (P<0.01). There were no significant differences for the
      various sleep parameters between the E-AED I and ECO groups. Therefore, VPA is
      capable of inducing sleep structure disorders in epileptic patients. In addition,
      these disorders begin 3 months following the administration of VPA, which
      indicates that these disorders may be associated with VPA-induced weight gain.

PMID- 24940417
TI  - Human umbilical cord blood-derived mesenchymal stem cell transplantation for the
      treatment of spinal cord injury.
AB  - The aim of the present study was to investigate the effects of human umbilical
      cord blood-derived mesenchymal stem cell (HUCB-MSC) transplantation on the
      functional restoration of spinal cord injury (SCI). A total of 46 adult Wistar
      rats were randomly divided into three groups: Injury (n=15), control (n=15) and
      transplantation (n=16). A SCI model was established using the modified Allen's
      method (vulnerating energy, 25 g/cm). The rats in the control and transplantation
      groups were injected at the site of the injury with physiological saline and HUCB
      MSC suspension, respectively. At week one, two and four following treatment, the
      behavior of the rats was evaluated using the Basso, Beattie, Bresnahan locomotor
      rating scale. In addition, immunohistochemistry (IHC) was performed on samples
      from the rats that had been sacrificed four weeks subsequent to the treatment.
      Recovery of the spinal cord nerve function was identified to be significantly
      different at week two and four following treatment (P<0.05), and IHC identified
      that at week four following treatment novel nerve cells were being produced.
      Thus, transplantation of HUCB-MSCs promoted the recovery of the damaged function
      of spinal cord nerves in rats with SCI.

PMID- 24940418
TI  - Pien Tze Huang inhibits hypoxia-induced epithelial-mesenchymal transition in
      human colon carcinoma cells through suppression of the HIF-1 pathway.
AB  - Hypoxia-induced activation of the hypoxia-inducible factor 1 (HIF-1) signaling
      pathway is frequently observed in solid tumors and is strongly associated with
      numerous pathophysiological processes, including the induction of epithelial
      mesenchymal transition (EMT), which result in cancer progression and metastasis.
      Thus, inhibiting EMT through the suppression of the HIF-1 pathway may be a
      promising strategy for anticancer chemotherapy. Pien Tze Huang (PZH), a well
      established traditional Chinese medicine has been prescribed for >450 years and
      has been used for centuries to clinically treat various types of human cancer. We
      previously reported that PZH suppresses multiple intracellular signaling pathways
      and thereby promotes the apoptosis of cancer cells and the inhibition of cell
      proliferation and tumor angiogenesis. In the present study, to further explore
      the mechanisms underlying the antitumor action of PZH, HCT-8 human colon
      carcinoma cells were cultured under hypoxic conditions and the effect of PZH on
      hypoxia-induced EMT was assessed. Hypoxia was found to induce EMT-associated
      morphological changes in HCT-8 cells, including loss of cell adhesion and the
      development of spindle-shaped fibroblastoid-like morphology. In addition, hypoxia
      was observed to reduce the expression of the epithelial marker E-cadherin, but
      increase that of the mesenchymal marker N-cadherin. In addition, hypoxia
      significantly enhanced HCT-8 cell migration and invasion and induced the
      activation of the HIF-1 pathway. However, treatment of the HCT-8 cells with PZH
      significantly inhibited the hypoxia-mediated EMT and HIF-1 signaling. These
      findings suggest that PZH inhibits hypoxia-induced cancer EMT through the
      suppression of the HIF-1 pathway, which may be one of the molecular mechanisms by
      which PZH exerts its antitumor activity.

PMID- 24940419
TI  - Relationship between p53 gene codon-72 polymorphisms and hypertrophic scar
      formation following caesarean section.
AB  - The aim of the present study was to determine the relationship between p53 gene
      codon-72 polymorphisms and hypertrophic scar formation following caesarean
      section (CS). Blood samples from 260 female patients were collected one week
      following a CS for the detection of p53 gene polymorphisms using a molecular
      beacon-coupled quantitative polymerase chain reaction technique. Patients had
      follow-ups for 12-18 months to observe the scar formation. From these
      observations, the relationship between the p53 codon-72 polymorphisms and
      hypertrophic scar formation occurrence was investigated. Among the patients with
      the CCC/CCC genotype, nine patients had hypertrophic scars and 46 patients showed
      normal healing, which is a ratio of 0.19. However, the follow-up investigations
      indicated that the presence of a homozygous or heterozygous C-to-G alteration at
      the codon-72 site in gene p53 resulted in 13 patients with hypertrophic scars and
      192 patients with normal healing, which is a ratio of 0.07. Therefore, these
      results indicate that patients with the CCC/CCC genotype had a higher risk of
      developing hypertrophic scars compared with that for patients with the CCC/CGC or
      CGC/CGC genotypes.

PMID- 24940420
TI  - Glycyrrhizin protects mice against renal ischemia-reperfusion injury through
      inhibition of apoptosis and inflammation by downregulating p38 mitogen-activated
      protein kinase signaling.
AB  - Ischemia-reperfusion (I/R) often leads to acute kidney injury, chronic renal
      failure and kidney transplantation failure. Glycyrrhizin is extracted from
      Glycyrrhiza glabra roots and is the predominant active component, which exhibits
      anti-inflammatory effects. However, to the best of our knowledge, the effect of
      glycyrrhizin on I/R-induced renal injury has not been investigated. In the
      present study, glycyrrhizin was demonstrated to attenuate renal I/R injury in
      mice via administration of glycyrrhizin, which suppressed the serum levels of
      creatinine and blood urea nitrogen 6 h following reperfusion; furthermore, the
      superoxide anions as well as the activity of superoxide dismutase within renal
      tissues was reduced by glycyrrhizin pretreatment. Moreover, the protein level of
      cleaved caspase-3, as well as its activity in renal tissue, was suppressed as a
      result of the glycyrrhizin pretreatment, indicating that glycyrrhizin inhibits
      I/R-induced renal cell apoptosis. In addition, glycyrrhizin pretreatment appeared
      to ameliorate I/R-induced renal injury via inhibition of inflammatory cell
      infiltration, as well as the production of pro-inflammatory cytokines, including
      tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-1beta and IL-6.
      The underlying molecular mechanism was investigated and it was shown that the
      activity of p38 mitogen-activated protein kinase signaling was downregulated as a
      result of glycyrrhizin administration. In conclusion, the present study indicated
      that glycyrrhizin provided significant protection against I/R-induced renal
      injury in mice by inhibiting inflammatory responses and renal cell apoptosis.
      Therefore, glycyrrhizin may be used in abdominal surgery and kidney
      transplantation for the prevention of renal I/R damage.

PMID- 24940421
TI  - Protective effects of hydrogen-rich saline in uncontrolled hemorrhagic shock.
AB  - Hydrogen is considered to be a novel antioxidant as it inhibits inflammation,
      removes oxygen-derived free radicals and reduces oxidative damage. This study
      investigated the effects of hydrogen-rich saline on plasma interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase (SOD) and
      malondialdehyde (MDA) in rats with uncontrolled hemorrhagic shock (UHS). The UHS
      model was induced by arterial bleeding and tail amputation. The rats were
      randomly divided into: Group A (sham-operated group), Group B [shock +
      intravenously (IV) injected saline], Group C (shock + IV-injected hydrogen-rich
      saline), Group D [shock + intraperitoneally (IP) injected saline] and Group E
      (shock + IP-injected hydrogen-rich saline). The survival rate 24 h after
      successful resuscitation was calculated. The mean arterial pressure and heart
      rate were recorded at 0, 30, 90 and 210 min. The plasma levels of IL-6, TNF
      alpha, SOD and MDA were measured at 0, 90 and 210 min. The survival rate of each
      group was 100% and the hemodynamics among the experimental groups were not
      significantly different. At 90 and 210 min, the levels of IL-6, TNF-alpha and MDA
      in Groups C and E were lower than those of Groups B and D, while the SOD levels
      were higher than those of Groups B and D (P<0.01). At 90 min, the levels of IL-6,
      TNF-alpha and MDA in Groups B and C were lower than those of Groups D and E,
      respectively (P<0.01). Hydrogen-rich saline has anti-inflammatory and anti
      oxidative effects in UHS. In conclusion, the results showed that itravenous
      injection of hydrogen-rich saline is more effective than intraperitonal
      injection.

PMID- 24940422
TI  - Sonographic measurement of renal size in patients undergoing chronic
      hemodialysis: Correlation with residual renal function.
AB  - Previous studies have reported that renal size may change when the function is
      compromised. However, it is not known whether sonographically measured renal size
      reflects the residual renal function (RRF) in patients undergoing chronic
      hemodialysis. A total of 140 patients undergoing chronic hemodialysis (>=3
      months) were investigated in the present study. The patients were divided into
      two groups according to the daily urine volume: Individuals with RRF (RRF+ group;
      >=200 ml; n=65) and without RRF (RRF- group; <200 ml; n=75). Renal sizes were
      measured using sonography and renal volumes were calculated with the ellipsoid
      formula. Univariable and multivariable stepwise forward logistic regression
      analyses were performed to examine the correlation between the presence of RRF
      and various variables. The results indicated that there were statistically
      significant differences (P<0.001) between the RRF+ and RRF- groups with regard to
      renal length, width, thickness and volume of the left (length, 7.9+/-1.2 vs.
      6.8+/-1.2 cm; volume, 60.0+/-26.7 vs. 40.2+/-18.1 ml, respectively) and right
      (length, 7.6+/-1.2 vs. 6.7+/-1.2 cm; volume, 50.2+/-26.5 vs. 33.9+/-15.3 ml,
      respectively) sides of the kidney. Multivariable stepwise forward logistic
      regression analyses showed that the mean renal length or volume and hemodialysis
      duration were independent predictors of the presence of RRF. Therefore, renal
      size assessment by ultrasonography may be useful for RRF evaluation in patients
      undergoing chronic hemodialysis.

PMID- 24940424
TI  - Effectiveness and safety profile of S-1-based chemotherapy compared with
      capecitabine-based chemotherapy for advanced gastric and colorectal cancer: A
      meta-analysis.
AB  - The aim of the present analysis was to compare the efficacy and safety profile of
      S-1-based chemotherapy (SBCT) versus capecitabine-based chemotherapy (CBCT) for
      advanced gastric cancer (AGC) and advanced colorectal cancer (ACRC). A meta
      analysis was performed, which included eligible randomized controlled trials
      (RCTs) that were identified using RevMan 5.1.0 software. A total of 1,064
      patients from 11 RCTs, comprising of 527 patients in the SBCT group and 537
      patients in the CBCT group, were included in the analysis. For AGC, the meta
      analysis of overall survival (OS) [hazard ratio (HR), 0.98; 95% confidence
      interval (CI), 0.85-1.12], time to progression (HR, 0.95; 95% CI, 0.80-1.12) and
      overall response rate (ORR) [odds ratio (OR), 1.06; 95% CI, 0.72-1.55] of
      patients in the SBCT group indicated no statistical significance when compared
      with those in the CBCT group. Furthermore, for ACRC, a pooled analysis
      demonstrated no significant difference between the SBCT and CBCT groups (OS: HR,
      0.82; 95% CI, 0.61-1.10; progression-free survival: HR, 0.79; 95% CI=0.60-1.04;
      ORR: OR, 1.27; 95% CI, 0.91-1.78). The statistically significant differences
      identified in the overall meta-analysis indicated a low incidence of grade 3-4
      hand-foot-syndrome (OR, 0.15; 95% CI, 0.06-0.36) in the SBCT group; however no
      statistically significant difference was observed in the incidence of grade 3-4
      anemia, thrombocytopenia, leucopenia, neutropenia, diarrhea, stomatitis or
      nausea/vomiting. The SBCT treatment exhibited similar efficacy and an
      approximately equivalent safety profile compared with the CBCT treatment and was
      an alternative to CBCT for patients with AGC or ACRC; however, further
      investigation is required to provide confirmation.

PMID- 24940423
TI  - FIZZ1 promotes airway remodeling through the PI3K/Akt signaling pathway in
      asthma.
AB  - Found in inflammatory zone 1 (FIZZ1) plays a vital role in pulmonary inflammation
      and angiogenesis. In addition, FIZZ1 plays a role in the early stages of airway
      remodeling in asthma by increasing the expression of alpha smooth muscle actin
      (alpha-SMA) and type I collagen. However, the role of FIZZ1 in the airway
      remodeling of asthma remains unclear. In the present study, FIZZ1 was identified
      to be upregulated in ovalbumin (OVA)-induced asthmatic mice, along with
      phosphorylated protein kinase B (Akt). Following FIZZ1 recombinant protein co
      culture in the murine lung epithelial-cell line, Akt phosphorylation was
      upregulated, however, following transfection with FIZZ1-small hairpin RNA, the
      phosphorylation levels were decreased. The variation in alpha-SMA and type I
      collagen expression levels was consistent with the Akt phosphorylation levels.
      Intratracheal administration of LY294002 and Akt inhibitor IV to the asthmatic
      mice was capable of reducing airway inflammation, downregulating the expression
      of alpha-SMA, type I collagen and fibronectin-1 and increasing the expression of
      E-cadherin. In conclusion, the present study demonstrated that FIZZ1 promoted
      airway remodeling in asthma via the phosphoinositide 3-kinase (PI3K)/Akt
      signaling pathway. Blocking the PI3K/Akt signaling pathway may attenuate the
      early stages of airway remodeling induced by OVA by regulating the abnormal
      process of epithelial-mesenchymal transition.

PMID- 24940425
TI  - Increasing gap junction coupling suppresses ibutilide-induced torsades de
      pointes.
AB  - Drug-induced torsades de pointes (TdP) is common with class III antiarrhythmic
      drugs. Increased transmural dispersion of repolarization (TDR) contributes
      significantly to the development of TdP. Gap junctions play an important role in
      maintaining TDR in long QT syndrome. The present study examined the effect of a
      gap junction enhancer, antiarrhythmic peptide 10 (AAP10), on ibutilide-induced
      TdP. Coronary-perfused rabbit ventricular wedge preparations were used to
      evaluate the effect of AAP10 on ibutilide-induced arrhythmia. Transmural
      electrocardiograms and action potentials were recorded simultaneously. Early
      afterdepolarizations (EADs), R-on-T extrasystole, TdP and changes in Tpeak-end
      (Tp-e) and the Tp-e/QT ratio were observed. Changes in the levels of non
      phosphorylated connexin 43 (Cx43) were measured by immunoblotting. Compared with
      those in the control group, the QT interval, Tp-e/QT and incidence rates of EAD
      and TdP increased with augmented dephosphorylation in the ventricular wedge
      preparations perfused with ibutilide under conditions of hypokalemia and
      hypomagnesemia. In the presence of AAP10, the incidence rates of EAD and TdP were
      reduced and the Tp-e/QT ratio decreased, with a parallel reduction in the level
      of non-phosphorylated Cx43. The results indicate that AAP10 suppressed ibutilide
      induced TdP under conditions of hypokalemia and hypomagnesemia by decreasing TDR.
      AAP10 reduced TDR, possibly by preventing the dephosphorylation of Cx43 and
      thereby increasing myocardial cell gap junction coupling.

PMID- 24940426
TI  - Effect of metformin on the human T98G glioblastoma multiforme cell line.
AB  - Metformin is a guanidine derivative found in Galega officinalis that is commonly
      used to treat diabetes mellitus. The mechanism of action of metformin involves
      regulation of the adenosine monophosphate-activated protein kinase/mammalian
      target of rapamycin signaling pathway, which is implicated in the control of
      protein synthesis and cell proliferation. This led to the hypothesis that
      metformin reduces the risk of cancer and slows tumor growth. Thus, in the present
      study, the effectiveness of metformin as an antiglioma agent was evaluated using
      the human T98G glioblastoma multiforme cell line. The viability of the T98G cells
      was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. Apoptosis was monitored by measuring caspase-3 levels, as well as by
      terminal deoxynucleotidyl transferase dUTP nick end labeling and staining with
      acridine orange and ethidium bromide. The results demonstrate that metformin
      reduced cell viability and caused apoptotic morphological changes in the T98G
      cells. Furthermore, the caspase-3 levels in the metformin-treated T98G cells were
      higher than those in the control cells. Metformin induced apoptosis in the T98G
      cell line in a concentration-dependent manner. Metformin may provide an important
      contribution to the treatment of glioblastoma multiforme.

PMID- 24940427
TI  - Enforced expression of microRNA-21 influences the replication of varicella-zoster
      virus by triggering signal transducer and activator of transcription 3.
AB  - Varicella-zoster virus (VZV) causes chronic pain and serious complications,
      including zoster paresis. However, the mechanism of VZV replication, a critical
      part of VZV pathogenesis, remains largely unknown and was investigated in the
      present study. The upregulation of microRNA-21 (miR-21) was identified following
      VZV infection in vitro by quantitative polymerase chain reaction. The hypothesis
      that the overexpression of miR-21 activates the signal transducer and activator
      of transcription 3 (STAT3) signaling pathway was validated by measuring the mRNA
      expression levels of STAT3 and the anti-apoptotic protein survivin in human
      malignant melanoma (MeWo) and human embryonic lung fibroblast (HELF) cell lines
      transfected with miR-21-mimic and comparing them with those in cells transfected
      with miR-control. To further study the interaction of miR-21, STAT3 and VZV
      replication, the effects of miR-21 overexpression and STAT3 knockdown were
      evaluated. Higher virus titers were detected when miR-21 was upregulated in
      vitro. Moreover, it was identified that significantly lower virus titers were
      present in MeWo cells in which STAT3 was knocked down. In addition, the
      overexpression of miR-21 did not stimulate VZV replication in the MeWo cell line
      when the STAT3 gene was silenced. Therefore, the observations of the present
      study indicate that the enforced expression of miR-21 promotes the replication of
      VZV by activating STAT3 in vitro.

PMID- 24940428
TI  - Protective effects of the combination of sodium ferulate and oxymatrine on cecal
      ligation and puncture-induced sepsis in mice.
AB  - The aim of this study was to investigate the effects of the combination of sodium
      ferulate (SF) and oxymatrine (OMT) on mice with cecal ligation and puncture (CLP)
      induced sepsis. Swiss male mice were randomly divided into a control group, CLP
      group, three SF + OMT groups (3.1+6.9; 6.2+13.8 and 12.3+27.7 mg/kg), SF (6.2
      mg/kg) group and OMT (13.8 mg/kg) group. Eight hours after the administration of
      the drugs, the survival rates and survival times of the animals were monitored.
      In addition, the lung wet/dry weight (W/D) ratio; alanine aminotransferase (ALT),
      aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the
      serum; the C-reactive protein (CRP), interleukin-6 (IL-6) and interferon-gamma
      (IFN-gamma) levels in the serum and lung and liver homogenates; and the
      malondialdehyde (MDA) and superoxidase dismutase (SOD) levels in the lung and
      liver homogenates were measured. The bacterial load in the serum was also
      studied. Following treatment with the combination of SF and OMT, the survival
      rate increased and the survival time was prolonged; CLP-induced increases in the
      lung W/D ratio and the levels of ALT, AST, LDH, CRP, IL-6, IFN-gamma and MDA were
      significantly reduced; and the SOD activity levels were increased, compared with
      those of the untreated animals with CLP-induced sepsis. These results indicated
      that the combination of SF and OMT induced protective effects against CLP-induced
      lethal sepsis of mice. The possible mechanism of these effects may be associated
      with the alleviation of systemic inflammation and diminishment of oxidative
      injury.

PMID- 24940429
TI  - Chloral hydrate-dependent reduction in the peptidoglycan-induced inflammatory
      macrophage response is associated with lower expression levels of toll-like
      receptor 2.
AB  - The aim of this study was to investigate the effect and mechanism of action of
      chloral hydrate on the peptidoglycan (PGN)-induced inflammatory macrophage
      response. The effect of chloral hydrate on the production of tumor necrosis
      factor alpha (TNF-alpha) and interleukin-6 (IL-6) by murine peritoneal
      macrophages with PGN-stimulation was investigated. In addition, RAW264.7 cells
      transfected with a nuclear factor-kappaB (NF-kappaB) luciferase reporter plasmid
      stimulated by PGN were used to study the effect of chloral hydrate on the levels
      NF-kappaB activity. Flow cytometry and western blotting were performed to
      investigate the expression levels of toll-like receptor 2 (TLR2) in the treated
      RAW264.7 cells. It was identified that chloral hydrate reduced the levels of IL-6
      and TNF-alpha produced by the peritoneal macrophages stimulated with PGN. The
      levels of NF-kappaB activity of the RAW264.7 cells stimulated by PGN decreased
      following treatment with chloral hydrate, which was associated with a reduction
      in the expression levels of TLR2 and reduced levels of TLR2 signal transduction.
      These data demonstrate that chloral hydrate reduced the magnitude of the PGN
      induced inflammatory macrophage response associated with lower expression levels
      of TLR2.

PMID- 24940430
TI  - Effects of progesterone on hippocampal ultrastructure and expression of
      inflammatory mediators in neonatal rats with hypoxic-ischemic brain injury.
AB  - Progesterone (PROG) has been shown to exhibit a protective function against
      hypoxic-ischemic brain damage. The aim of the present study was to study the
      effects of PROG in a neonatal rat model of hypoxic-ischemic brain injury. A total
      of 30 Wistar rats, aged 7 days, were randomly divided into three groups: Sham,
      model and PROG. The rats in the model and PROG groups underwent a left common
      carotid artery ligation and were placed in a sealed container at 37 degrees C
      with 8% O2 and 92% N2 gas mixtures for 2.5 h to establish animal models of
      hypoxic-ischemic encephalopathy. The rats in the PROG group were
      intraperitoneally treated with 8 mg/kg PROG solution 30 min prior to the
      induction of hypoxia-ischemia. All animals were sacrificed after 24 h and
      neuronal changes were observed with electron microscopy to investigate the
      hypoxic-ischemic brain damage. The protein and mRNA expression levels of tumor
      necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) in the
      hippocampus were detected by immunohistochemistry and quantitative polymerase
      chain reaction, respectively. The results revealed that the neuronal structures
      in the sham group were normal. The neuronal structures in the model group
      exhibited cavitation changes, but these were reduced following PROG
      administration. The protein and mRNA expression levels of TNF-alpha and NF-kappaB
      in the hippocampal neurons were increased in the model group, and pretreatment
      with 8 mg/kg PROG was shown to reduce the expression levels of these inflammatory
      mediators. Therefore, PROG was shown to exert an important protective function in
      hypoxic-ischemic brain injury by inhibiting the cascade of inflammatory injury
      induced by TNF-alpha and NF-kappaB.

PMID- 24940432
TI  - Development and validation of a nutritional and nursing risk assessment method
      for diabetic patients.
AB  - The present study aimed to develop and evaluate a nutritional and nursing risk
      assessment method for diabetic inpatients to improve healthcare and risk
      management. Diabetic inpatients diagnosed according to the World Health
      Organization guidelines, together with their nursing staff, were divided into two
      groups for nutritional and nursing risk assessment. Data from one group were used
      to establish the assessment method, and data from the other group were used to
      evaluate the reliability and effectiveness of the method. To establish the
      method, various risk variables in the nutritional and nursing processes were
      evaluated by logistic regression analysis; the score and probability of the risk
      variables were determined based on odds ratios. The overall nutritional and
      nursing risk for individual inpatients was then judged by the accumulated scores.
      The analysis showed that there were a number of risk factors, including age and
      body mass index. The risk was shown to increase with increasing score for the
      inpatients, and the chi2 test (P<0.01) was used to indicate a significant
      association. When the score was 50, the sensitivity and specificity of the method
      used to detect the nutritional and nursing risk were 88.3 and 66.5%,
      respectively, with predictive positive and negative rates of 12.83 and 98.53%,
      respectively. Therefore, the method is simple, cost-effective and fast; it can be
      used to screen a large number of patients by nursing staff and can also be used
      by patients themselves. Overall, the method is an effective and practicable
      nutritional and nursing risk assessment and educational tool.

PMID- 24940431
TI  - Apoptosis of human gastric cancer SGC-7901 cells induced by podophyllotoxin.
AB  - Numerous studies have demonstrated that podophyllotoxin and its derivatives
      exhibit antitumor effects. The aim of the present study was to investigate SGC
      7901 cell apoptosis and the underlying mechanism induced by podophyllotoxin. SGC
      7901 cells were treated with varying concentrations of podophyllotoxin. MTT
      assays and flow cytometry were used to evaluate the effects of podophyllotoxin on
      the proliferation and apoptosis of SGC-7901 cells, while fluorescence inverted
      microscopy was used to observe the morphology of SGC-7901 cells that had been
      dyed with Hoechst 33258. In addition, laser scanning confocal microscopy was used
      to analyze the mitochondrial membrane potential (MMP) of SGC-7901 cells dyed with
      Rhodamine 123. Western blotting was performed to analyze the expression levels of
      cytochrome c (cyt-c), caspase-9 and caspase-3 in the SGC-7901 cells. The results
      indicated that podophyllotoxin was capable of inhibiting growth and inducing the
      apoptosis of SGC-7901 cells in a dose-dependent manner, causing cell cycle arrest
      at the G2/M phase. After 48 h of treatment, the apoptotic morphology of SGC-7901
      cells was clear, exhibiting cell protuberance, concentrated cytoplasms and
      apoptotic bodies. Following 24 h of treatment, the MMP of the SGC-7901 cells
      decreased. In addition, after 48 h, the expression of cyt-c was shown to be
      upregulated, while the expression levels of pro-caspase-9 and pro-caspase-3 in
      the SGC-7901 cells were shown to be downregulated. In conclusion, apoptosis can
      be induced in SGC-7901 cells by podophyllotoxin, potentially via a mitochondrial
      pathway, indicating that podophyllotoxin may be a potent agent for cancer
      treatment.

PMID- 24940433
TI  - Effect of Quanzhenyiqitang on apoptosis of alveolar macrophages and expression of
      histone deacetylase 2 in rats with chronic obstructive pulmonary disease.
AB  - This study aimed to investigate the effect of Quanzhenyiqitang on alveolar
      macrophages (AMs) in a rat model of chronic obstructive pulmonary disease (COPD).
      In addition, the induction of apoptosis and regulation of histone deacetylase 2
      (HDAC2) was studied to elucidate the underlying mechanisms of Quanzhenyiqitang
      treatment of COPD. Quanzhenyiqitang-treated serum was applied to AMs obtained
      from rats with COPD. A blank (control) group, an untreated serum group and an
      aminophylline group were also observed to evaluate the differences in AM
      apoptosis status, as well as the expression levels of caspase-9, caspase-8 and
      HDAC2. Compared with the control group, Quanzhenyiqitang-treated serum resulted
      in higher levels of caspase-9 and caspase-8 expression, increased apoptosis of
      AMs and increased expression of HDAC2 by AMs. In conclusion, Quanzhenyiqitang is
      capable of inducing apoptosis of AMs, which are the primary inflammatory cells in
      COPD, and modulating the expression of the important inflammatory factor HDAC2,
      producing an overall anti-inflammatory effect.

PMID- 24940434
TI  - Transthyretin as a novel candidate biomarker for preeclampsia.
AB  - Preeclampsia (PE) is considered to be a potentially fatal complication during
      pregnancy. However, no effective laboratory assessment has been developed to
      enable early diagnosis and monitoring of PE. The present study aimed to identify
      differentially expressed transthyretin (TTR) during severe PE and evaluate TTR as
      a possible biomarker of this disease. TTR levels were determined in the different
      gestational weeks of normal pregnancy (before 20 weeks, n=41; after 20 weeks,
      n=39) using enzyme-linked immunosorbent assay (ELISA). TTR concentrations in
      pregnant females with severe PE (n=43) were compared with those in healthy
      matched control subjects (n=37) using western blot analysis and ELISA. The median
      TTR concentration during severe PE in each month of gestation was significantly
      lower than the concentrations recorded during normal pregnancy. TTR levels in
      females with severe PE were significantly downregulated compared with the control
      subjects (P<0.001; area under the curve, 0.834-0.967). Thus, TTR may be used as a
      potential biomarker of PE.

PMID- 24940435
TI  - Association between pelvic organ prolapse and stress urinary incontinence with
      collagen.
AB  - The aim of the present study was to investigate the ultrastructure and content of
      collagen in uterosacral ligaments and paraurethral tissues in patients with
      pelvic organ prolapse (POP) and stress urinary incontinence (SUI), analyzing the
      association between POP and collagen dysfunction. The study comprised three
      groups: Control, POP and POP with SUI (n=30 per group). Histological
      characteristics of collagen fiber were observed and the diameters were measured
      using light and electron microscopy to determine the Type I and Type III collagen
      content of the main ligament in the urethral specimens. In the POP and POP with
      SUI groups, observations included diffuse atrophy of smooth muscles, active
      fibroblast metabolism, swollen mitochondria and visible Golgi apparatus. The
      collagen fibril diameters in the cardinal ligaments, uterosacral ligaments and
      paraurethral tissues were significantly greater in the POP and POP with SUI
      groups compared with those in the control group (P<0.01). In addition, the
      expression levels of Type I and Type III collagen were significantly lower in the
      POP and POP with SUI groups when compared with the control group (P<0.01). In the
      POP with SUI group, pelvic tissues were frail, resulting in smooth muscle bundles
      comminuting and arranging in a disorganized pattern. Fibroblast and myoblast
      metabolisms were active and new microvascular cells were weak. However, the
      collagen fibril diameter increased. Thus, collagen and ultrastructural changes in
      the pelvic floor may be associated with the development of POP and SUI.

PMID- 24940436
TI  - Severe sepsis: Low expression of the renin-angiotensin system is associated with
      poor prognosis.
AB  - Severe sepsis has a high fatality rate, but no clinical indices for prognosis
      have been established. In recent years, the renin-angiotensin system (RAS) has
      received considerable attention. However, clinical data on RAS are inconsistent.
      Therefore, the aim of the present study was to assess the significance of RAS in
      the prognosis of sepsis. Blood samples were collected from patients, who met the
      diagnostic criteria of severe sepsis, on day 1 (D1) and 3 (D3). For each sample,
      the levels of angiotensin II (AngII), angiotensin-converting enzyme (ACE) and
      additional indices were measured. Patients were monitored for 28 days. On the D1
      of inclusion, the average Acute Physiology and Chronic Health Evaluation II
      (APACHE II) score was 22.2 and the Sepsis-related Organ Failure Assessment (SOFA)
      score was 6.1. Logistic regression analysis revealed that mortality-associated
      variables included the APACHE II score on D1, the SOFA score on D1, high lactic
      acid levels on D3 and low AngII and ACE levels on D1 and D3. AngII levels (<86.1
      ng/ml) on D1 had a sensitivity of 88.2% and specificity of 77.3% for predicting
      mortality. ACE levels (<39.2 ng/ml) on D1 had a sensitivity of 88.2% and
      specificity of 72.7% for predicting mortality. These two indices were better than
      the APACHE II and SOFA scores. Therefore, low expression levels of AngII and ACE
      are valuable in predicting the mortality of patients with severe sepsis.

PMID- 24940437
TI  - Effects of metformin on endothelial function in type 2 diabetes.
AB  - The aim of the present study was to examine the effect of metformin on
      endothelial function in patients with type 2 diabetes mellitus (T2DM). In total,
      93 patients with T2DM and dissatisfactory glycemic control were randomly assigned
      to the metformin and pioglitazone groups and changes in vascular endothelial
      function were subsequently observed. Blood sugar levels and the insulin
      resistance (IR) index of the patients prior to treatment were lower than those
      following 12 months of treatment. In addition, fasting and postprandial insulin
      levels and the insulin function index were higher compared with those obtained
      following 12 months of treatment (P<0.05). Following 12 months of treatment, the
      body mass index (BMI) in the metformin group was lower than that in the
      pioglitazone group (P<0.05). Vascular endothelial function had improved in the
      groups following 12 months of treatment, when compared with the levels prior to
      treatment (P<0.05). Following 12 months of treatment, endothelial function in the
      metformin group had improved markedly compared with that in the pioglitazone
      group (P<0.05). Therefore, the administration of metformin and pioglitazone in
      patients with T2DM may improve insulin function, reduce the role of IR and
      improve endothelial function. Metformin is more successful than pioglitazone in
      reducing BMI and improving endothelial function.

PMID- 24940439
TI  - Contrast-enhanced ultrasound analysis of tissue perfusion in tumor-bearing mice
      following treatment with endostatin combined with radiotherapy.
AB  - The aim of this study was to observe the effects of Endostar (recombinant human
      endostatin) and radiotherapy, singly or in combination, on blood flow in mouse
      tumour tissue using ultrasound imaging. The ultrasound contrast agent, SonoVue,
      was used for the contrast-enhanced ultrasound examinations. SonoLiver software
      was used to analyse dynamic vascular patterns (DVPs) in the contrast process.
      Blood perfusion data were collected and statistical analysis was performed for
      data processing. Results were presented as DVP curves and quantitative
      parameters. Quantitative parameters showed statistically significant (P<0.05)
      differences in peak strength, rise time, time to peak and mean transit time among
      the various treatment groups. Changes in tumour blood perfusion were quantified
      by the assessment of contrast-enhanced ultrasound parameters. The results
      indirectly reflected the degree of change in angiogenesis in the tumour following
      experimental intervention. Ultrasound contrast imaging effectively showed the
      extent of the changes in vascularity and flow state. Therefore, contrast-enhanced
      ultrasound is suitable for use as an indicator of blood flow changes in an
      experimental model.

PMID- 24940438
TI  - Saikosaponin-d affects the differentiation, maturation and function of monocyte
      derived dendritic cells.
AB  - Saikosaponin-d (Ssd) is a triterpenoid saponin derived from Bupleurum falcatum
      L., which has been shown to exhibit a variety of pharmacological properties,
      including anti-inflammatory, antibacterial and antiviral properties. The aim of
      the present study was to investigate the effect of Ssd on the differentiation,
      maturation and function of human monocyte-derived dendritic cells (DCs) isolated
      from condylomata acuminata patients. The results of the present study
      demonstrated that Ssd reduced the differentiation of DCs, as evidenced by
      decreased expression levels of cluster of differentiation (CD)1a, CD80 and CD86
      molecules and increased CD14 expression. Expression levels of the mannose
      receptor and CD32 were also significantly elevated, which was associated with
      enhanced fluorescein isothiocyanate-dextran endocytic activity. Furthermore, Ssd
      treatment promoted DC maturation by increasing the expression levels of CD40,
      CD83, CD80 and CD86. In addition, the function of mature DCs, including the
      secretion of IL-12 and the stimulation of lymphocyte proliferation, was
      significantly increased following Ssd administration. In conclusion, the present
      study indicated that Ssd exhibited immunomodulatory effects and may be a novel
      potent chemopreventive drug candidate for the treatment of condylomata acuminata.

PMID- 24940440
TI  - Comparison of ferulic acid content in Radix Angelicae Sinensis, Danggui-Buxue
      Tang and Danggui-Sini-Tang.
AB  - The aim of the present study was to determine the ferulic acid (FA) content of
      Radix Angelicae Sinensis (AS), Danggui-Buxue-Tang (DBT) and Danggui-Sini-Tang
      (DST) using the same ultra performance liquid chromatography system and method.
      FA was eluted using an Acquity BEH C18 column (100*2.1 mm inner diameter; 1.7
      MUm). A mobile phase of methanol and 0.5% acetic acid was used and a flow rate of
      0.3 ml/min was selected. The calibration curve exhibited a good linear regression
      (R2=0.9997). The inter- and intra-day precision measurements of FA ranged between
      0.27 and 3.03% and the recovery ranged between 98.44 and 101.64% with relative
      standard deviation (RSD) values <=4.73%. The method was reliable and simple. The
      results of the chromatographic analyses indicate that the FA contents of the DBT
      and DST decoctions were increased compared with that of AS due to the presence of
      other herbs.

PMID- 24940441
TI  - Analysis of the full-length genome of a novel strain of the H7N9 avian influenza
      virus.
AB  - The aim of the present study was to analyze the evolution and variation of a
      novel strain of the avian influenza virus. The virus-positive specimens
      [A/Changsha/2/2013 (H7N9)] from a patient infected with the novel avian influenza
      A (H7N9) virus was amplified by reverse transcription-PCR and the full genome was
      sequenced. The sequencing results were submitted to GenBank and then analyzed by
      phylogenetic tree analysis using BioEdit and Mega5 software. The phylogenetic
      tree of the hemagglutinin (HA) and neuraminidase genes revealed that
      A/Changsha/2/2013 (H7N9) and all the new H7N9 viruses in 2013 were in a large
      cluster, and their nucleotide evolutionary distances were closely associated.
      Phylogenetic tree analyses of the nucleoprotein and nonstructural genes
      demonstrated two main branches. One branch contained novel H7N9 viruses isolated
      from avian, human and environmental sources in different regions. The other
      branch contained three novel H7N9 virus strains isolated from environmental
      sources in Shanghai. All the phylogenetic trees of the matrix protein, polymerase
      acidic, polymerase basic protein 1 and polymerase basic protein 2 genes also
      showed two branches, with each branch including the novel H7N9 virus strains
      isolated from avian, human and environmental sources in different regions.
      Molecular characterization demonstrated that 52 novel H7N9 viruses sequenced to
      date contain the G228S and G186V mutations in the receptor binding site of the HA
      protein. The full-genome sequences of A/Changsha/2/2013 and analyses of its
      molecular characteristics suggest that the A/Changsha/2/2013 H7N9 virus strain
      has molecular characteristics that may facilitate adaptation of the virus to
      mammalian hosts and may even bind to human receptors.

PMID- 24940442
TI  - Effect of tissue factor knockdown on the growth, invasion, chemoresistance and
      apoptosis of human gastric cancer cells.
AB  - This study aimed to explore the role of tissue factor (TF) and evaluate its
      antitumor effects in the biological processes of gastric cancer cells using the
      application of RNA interference technology to silence TF in the SGC7901 gastric
      cancer cell line. Specific small interfering RNA (siRNA) designed for targeting
      human TF was transfected into SGC7901 cells. The expression levels of TF in the
      cells were detected by reverse transcription-polymerase chain reaction. Cell
      proliferation and chemosensitivity were measured by Cell Counting Kit-8. The
      metastatic potential of the SGC7901 cells was determined by Transwell experiments
      and wound-healing assays. Cell apoptosis was assessed by Annexin V-fluorescein
      isothiocyanate/propidium iodide double-staining method. The expression levels of
      TF mRNA were significantly reduced by the TF-siRNA in the SGC7901 cells,
      resulting in the suppression of cell proliferation, chemoresistance and invasion,
      and subsequently the induction of cell apoptosis. TF knockdown with siRNA
      inhibits the growth, invasion and chemoresistance and enhances the apoptosis of
      SGC7901 cells, providing a potential approach for gene therapy against human
      gastric cancer.

PMID- 24940443
TI  - Effect of dexmedetomidine-etomidate-fentanyl combined anesthesia on somatosensory
      and motor-evoked potentials in patients undergoing spinal surgery.
AB  - This aim of the present study was to evaluate the effects of dexmedetomidine
      (DEX) on the intraoperative monitoring of somatosensory-evoked potentials (SEPs)
      and motor-evoked potentials (MEPs) in patients undergoing spinal surgery. A total
      of 36 patients who received spinal surgery under general anesthesia were randomly
      divided into two groups (n=18 per group), group C, the test group and group D,
      the control group, and these groups were subjected to a matching anesthesia
      induction. In brief, the anesthesia was administered via injection of etomidate
      and fentanyl; once the patients were unconscious, a laryngeal mask airway (LMA)
      was inserted, SEPs and MEPs were monitored and the collected data were considered
      to be basic data. Cisatracurium was subsequently injected and an endotracheal
      tube (7#) was inserted to replace the LMA. The following procedures were
      conducted for anesthesia maintenance: Group C, the anesthesia was maintained via
      target-controlled infusion of etomidate and intermittent injection of fentanyl;
      and group D, DEX (0.5 MUg/kg) was injected over a duration of 10 min and then
      pumped at a rate of 0.5 MUg/kg/h. In the two groups, all of the other drugs used
      were the same and a muscle relaxant was not administered. The bispectral index
      was maintained between 45 and 55 during surgery, and the SEPs and MEPs were
      monitored continuously until the surgery was completed. No significant difference
      in duration and amplitude of the SEPs (P15-N20) was identified between group C
      and D (P>0.05). Furthermore, the MEPs were monitored in the two groups at
      specific durations and no significant difference was observed between the two
      groups (P>0.05). The SEPs and MEPs were maintained in the patients who were
      administered with the DEX-etomidate-fentanyl combined anesthesia during spinal
      surgery.

PMID- 24940445
TI  - Lateral ventricular cystic meningioma: 2 rare case reports.
AB  - Cystic meningioma is an uncommon meningioma variant that is often difficult to
      distinguish from other intra-axial tumors, including necrotic gliomas. Cystic
      meningiomas located in the ventricle are particularly rare and may be
      misdiagnosed with other brain tumors, including ependymoma, choroid plexus
      papilloma and neurocytoma, due to its location. The present study discusses two
      cases of lateral ventricular meningiomas, which exhibited intratumoral or
      peritumoral cystic changes on magnetic resonance imaging scans. The two patients
      underwent surgical treatment and histological examination confirmed one case of
      metaplastic meningioma and the other case of psammomatous meningioma. The two
      patients were middle-aged females and had been misdiagnosed prior to surgery.
      Although this clinical entity is rare, the diagnosis of meningioma should be
      considered, particularly in middle-aged female patients.

PMID- 24940444
TI  - Gypenoside attenuates hepatic ischemia/reperfusion injury in mice via anti
      oxidative and anti-apoptotic bioactivities.
AB  - Gynostemma pentaphyllum is a traditional Chinese medicine that has previously
      been used for the treatment of chronic inflammation, hyperlipidemia and liver
      disease. Gypenoside (GP), the predominant component of Gynostemma pentaphyllum,
      exhibits a therapeutic effect on chronic hepatic injury, fibrosis and fatty liver
      disease via its anti-inflammatory and anti-oxidant activity. However, the effect
      of GP on ischemia/reperfusion (I/R)-induced hepatic injury has, to the best of
      our knowledge, not previously been investigated. In the present study, a hepatic
      I/R-injury model was successfully established using C57BL/6 mice. In the
      treatment group, 50 mg/kg GP was administered orally 1 h prior to ischemia.
      Following hepatic I/R, the levels of hepatic lipid peroxidation and serum alanine
      aminotransferase increased, while the ratio of hepatic glutathione (GSH):oxidized
      GSH was reduced, which was effectively attenuated by pretreatment with GP.
      Furthermore, an increased protein expression of heme oxygenase-1 in the liver
      tissues of the I/R mice was attenuated by the administration of GP. In addition,
      the present study indicated that treatment with GP suppressed the I/R-induced
      increase in the pro-apoptotic protein levels of Bax and cytochrome c and the
      activity of caspase-3/8, as well as the I/R-induced decrease in the levels of
      anti-apoptotic protein Bcl-2. In conclusion, the present study indicated that GP
      effectively protected against I/R-induced hepatic injury via its anti-oxidative
      and anti-apoptotic bioactivity.

PMID- 24940446
TI  - EGFP gene transfection into the synovial joint tissues of rats with rheumatoid
      arthritis by ultrasound-mediated microbubble destruction.
AB  - The aim of the present study was to explore the feasibility of enhancing green
      fluorescent protein (EGFP) gene transfection into the synovial joint tissues of
      rats with rheumatoid arthritis (RA) by ultrasound-mediated microbubble
      destruction. An optimal SonoVue dose was determined using 40 normal rats
      categorized into five groups according to the various doses of microbubbles used.
      At 1 week after ultrasound irradiation, the rats were sacrificed. Damage to the
      joint synovial tissues was observed with hematoxylin and eosin histopathological
      staining under a microscope. A further 44 normal rats were used to establish a
      rat model of RA, and were then categorized into four groups: EGFP, ultrasound +
      EGFP, microbubbles + EGFP and ultrasound + microbubbles + EGFP. The last group
      was irradiated with ultrasound for 10 min following the injection of 300 MUl
      SonoVue and 10 MUg EGFP into the joint cavity. Rats were sacrificed after 3 days
      and synovial tissue was collected from the knee joints for observation of EGFP
      with fluorescence microscopy and analysis by quantitative polymerase chain
      reaction. EGFP expression was observed in the synovial tissues of all groups.
      However, high EGFP expression levels were observed in the ultrasound +
      microbubbles + EGFP group. No statistically significant differences (P>0.05) were
      observed in the EGFP expression levels between the EGFP, ultrasound + EGFP and
      microbubbles + EGFP groups. However, EGFP expression levels in the EGFP,
      ultrasound + EGFP and microbubbles + EGFP groups significantly differed (P<0.05)
      from that in the ultrasound + microbubbles + EGFP group. Therefore, ultrasound
      mediated microbubble destruction improved EGFP transfection efficiency into the
      joint synovial tissues of rats with RA.

PMID- 24940447
TI  - Effects of a gemcitabine plus platinum regimen combined with a dendritic cell
      cytokine induced killer immunotherapy on recurrence and survival rate of non
      small cell lung cancer patients.
AB  - The aim of the present study was to investigate the effects of a gemcitabine plus
      platinum (GP) regimen combined with dendritic cell-cytokine induced killer (DC
      CIK) immunotherapy on the recurrence and survival rate in patients with non-small
      cell lung cancer (NSCLC). Patients (n=157) with stage III NSCLC that had received
      surgery were randomly divided into a control group and an observation group. The
      control group was administered with a GP regimen and the observation group
      received GP chemotherapy that was based on DC-CIK cell immunotherapy in addition
      to SC-CIK cell immunotherapy here. The two groups were followed up for 36 months
      and their postoperative cellular immune function, disease-free survival time,
      cumulative recurrence rate and cumulative survival rate was analyzed. The
      percentages of CD3+CD4+ T lymphocytes, natural killer cells and the CD4/CD8 ratio
      were identified to be significantly increased following treatment compared with
      those observed prior to treatment in the control and observation groups;
      conversely, the CD3+CD8+ T lymphocyte percentage decreased significantly
      (P<0.05). Furthermore, the results of the patients in the observation group were
      significantly better compared with the control group based on these indicators
      (P<0.05). The median disease-free survival time of patients in the observation
      group (28 months) was identified to be significantly longer than that of the
      control group (22 months; P<0.05), the three-year cumulative recurrence rate in
      the observation group (47.37%) was significantly lower than that of the control
      group (76.92%; P<0.05) and the three-year cumulative survival rate of the
      patients in the observation group (58.23%) was significantly higher than that of
      the control group patients (37.14%; P<0.05). In conclusion, the GP regimen
      combined with DC-CIK immunotherapy significantly improved the immune cell
      function in the postoperative NSCLC patients, in addition to reducing
      postoperative tumor recurrence and prolonging the survival time of patients with
      NSCLC.

PMID- 24940448
TI  - Effect of gamma-tocotrienol in counteracting oxidative stress and joint damage in
      collagen-induced arthritis in rats.
AB  - Tocotrienols exhibit a significant anti-inflammatory and antioxidant effect in
      numerous human diseases. However, the anti-inflammatory and antioxidant effects
      of tocotrienols in arthritic conditions are not well documented. Therefore, the
      effect of gamma-tocotrienol supplementation against oxidative stress and joint
      pathology in collagen-induced arthritis in rats was investigated in the present
      study. Adult female Dark Agouti rats were randomly divided into groups: Control,
      gamma-tocotrienol alone, arthritis alone and arthritis with gamma-tocotrienol.
      Arthritis was induced using 4 mg/kg body weight collagen in complete Freund's
      adjuvant. The rats were treated orally with 5 mg/kg body weight of gamma
      tocotrienol between day 21 and day 45. After 45 days, serum C-reactive protein
      (CRP), tumor necrosis factor (TNF)-alpha, superoxide dismutase (SOD) and total
      glutathione (GSH) assays were conducted. gamma-tocotrienol significantly reduced
      the arthritis-induced changes in body weight, CRP, TNF-alpha, SOD and the total
      GSH levels. There was a significant reduction in the arthritis-induced
      histopathological changes in the gamma-tocotrienol treatment group. The data
      indicated that administration of gamma-tocotrienol resulted in a significant
      antioxidant and anti-inflammatory effect on collagen-induced arthritis;
      therefore, gamma-tocotrienol may have therapeutic potential as a long-term anti
      arthritic agent in rheumatoid arthritis therapy.

PMID- 24940449
TI  - Mechanisms of ischemic stroke in patients with intracranial atherosclerosis: A
      high-resolution magnetic resonance imaging study.
AB  - High-resolution magnetic resonance imaging (HRMRI) has a unique ability to
      provide an evaluation of the intracranial artery wall. This study aimed to
      investigate the possible mechanisms of ischemic stroke in patients with
      intracranial atherosclerosis using HRMRI. HRMRI was performed on 55 patients (38
      male and 17 female) with acute cerebral infarction to investigate the lumen
      intruding plaque at the stenotic portion of the middle cerebral artery (MCA) and
      basilar artery (BA) and to attempt to identify the mechanisms of stroke.
      Penetrating artery disease (PAD) was diagnosed in 20 patients (36%) and large
      artery atherosclerosis (LAA) was diagnosed in 35 patients, including 19 with
      parent artery plaques occluding a penetrating artery (POPA; 35%) and 16 with
      artery-to-artery embolisms (29%). Patients with PAD had a higher frequency of
      hypertension compared with that of the patients with LAA (80 versus 29%;
      P<0.001), and patients with LAA had a higher frequency of diabetes compared with
      that of the patients with PAD (40% versus 15%; P=0.054). Magnetic resonance
      angiography revealed mild to moderate stenosis in the patients with POPA, while
      border zone infarction and artery-to-artery embolism occurred in the majority of
      the patients with severe stenosis or occlusion of the MCA and BA. HRMRI has the
      ability to identify the mechanisms of intracranial atherosclerotic ischemic
      stroke through the detection of luminal plaques.

PMID- 24940450
TI  - Sorafenib-based therapy in HER2-negative advanced breast cancer: Results from a
      retrospective pooled analysis of randomized controlled trials.
AB  - A standard systemic therapy for patients with human epidermal growth factor
      receptor 2 (HER2)-negative advanced breast cancer (ABC) is yet to be identified.
      Sorafenib has been developed for the treatment of solid tumors, including breast
      cancer, as an oral multikinase inhibitor with antiangiogenic and
      antiproliferative activity. The aim of the present study was to assess the
      efficacy and safety of sorafenib in patients with HER2-negative ABC by performing
      a meta-analysis. A literature search was applied to databases, including PubMed,
      EMBASE, the Cochrane Library Databases, American Society of Clinical Oncology and
      the European Society for Medical Oncology, with the search terms 'advanced breast
      cancer' and 'sorafenib' and relevant studies were selected for analysis. The data
      extracted from the selected studies included progression-free survival (PFS),
      time to progression (TTP), overall survival (OS) and overall response rate (ORR).
      Major adverse events (AEs) were also analyzed. A total of four randomized
      controlled trials containing 844 cases were identified. Combined results revealed
      that when compared with chemotherapy (or with anti-hormone receptor therapy)
      alone, sorafenib-based therapy significantly increased the PFS [hazard ratio
      (HR), 0.78; 95% confidence interval (CI), 0.54-1.02] and TTP (HR, 0.74; 95% CI,
      0.50-0.97), but not the OS (HR, 0.95; 95% CI, 0.75-1.15) and ORR (relative risk,
      1.19; 95% CI, 1.01-1.39). In addition, the incidence of grade 3/4 AEs, including
      hand-foot skin syndrome, anemia, fatigue, rash and stomatitis, were significantly
      increased in patients that received sorafenib-based therapy. Therefore, the
      results from the current meta-analysis indicated that sorafenib-based therapy
      improved the PFS and TTP in patients with HER2-negative ABC, but not the OS and
      ORR. In addition, combination treatment was associated with increased toxicities
      and frequently required dose reductions.

PMID- 24940451
TI  - Bacteriology and drug susceptibility analysis of pus from patients with severe
      intra-abdominal infection induced by abdominal trauma.
AB  - The aim of the present study was to retrospectively analyze the bacteriology and
      drug susceptibility of pus flora from abdominal trauma patients with severe intra
      abdominal infection (SIAI). A total of 41 patients with SIAI induced by abdominal
      trauma were enrolled in the study, from which 123 abdominal pus samples were
      obtained. The results from laboratory microbiology and drug sensitivity were
      subjected to susceptibility analysis using WHONET software. A total of 297
      strains were isolated in which Gram-negative bacteria, Gram-positive bacteria and
      fungi accounted for 53.5 (159/297), 44.1 (131/297) and 0.7% (2/297),
      respectively. Anaerobic bacteria accounted for 1.7%. The five predominant
      bacteria were Escherichia coli (E. coli), Staphylococcus aureus (S. aureus),
      Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis and Pseudomonas
      aeruginosa (P. aeruginosa). E. coli was highly susceptible to cefoperazone (91%)
      and imipenem (98%), while Gram-positive cocci were highly susceptible to
      teicoplanin (100%) and linezolid (100%). S. aureus was 100% susceptible to
      vancomycin and K. pneumoniae was highly susceptible to imipenem (100%) and
      amikacin (79%). P. aeruginosa was the most susceptible to ciprofloxacin (90%).
      Gram-negative bacterial infection was present in the majority of cases of SIAI.
      However, a large number of patients were infected by Gram-positive bacteria,
      particularly S. aureus that exhibited significant resistance to penicillin
      (100%), oxacillin (100%) and a third-generation cephalosporin antibiotic
      cefotaxime (95%). Amongst the pathogenic bacteria that cause SIAI, both Gram
      negative and Gram-positive bacteria account for a high proportion, so high-level
      and broad-spectrum antibiotics should be initially used.

PMID- 24940452
TI  - Orbital and adnexal tuberculosis: a case series from a South Indian population.
AB  - BACKGROUND: Orbital tuberculosis (OTb) is rare and may be regarded as a
      manifestation of extrapulmonary tuberculosis. We report an interesting case
      series of six patients with varied presentations of orbital and adnexal
      tuberculosis in a South Indian patient population. RESULTS: A retrospective,
      interventional case series of six patients diagnosed with orbital and adnexal
      tuberculosis on the basis of clinical, radiological and histopathological
      evaluations between 2010 and 2013 was performed. Among the six patients with
      histopathologically proven OTb, five were women. The varied presentations
      included tubercular dacryoadenitis (two cases), classical periostitis (two
      cases), OTb with bone involvement (one case) and ocular adnexal tuberculosis (one
      case). Systemic involvement was seen in one case. All cases were treated with a
      regimen of antitubercular therapy (ATT). CONCLUSIONS: OTb, though rare, should
      form a part of the differential diagnosis of orbital lesions in a high
      tuberculosis (TB) endemic country like ours. Biopsy still remains the mainstay of
      diagnosis.

PMID- 24940453
TI  - Stricture length and etiology as preoperative independent predictors of
      recurrence after urethroplasty: A multivariate analysis of 604 urethroplasties.
AB  - INTRODUCTION: We determine the preoperative identifiable risk factors during
      staging that predict stricture recurrence after urethroplasty. METHODS: We
      conducted a retrospective review of all urethroplasties performed at a Canadian
      tertiary referral centre from 2003 to 2012. Failure was defined as a recurrent
      stricture <16 Fr on cystoscopic assessment. Multivariate analysis was calculated
      by Cox proportional hazard regression. RESULTS: In total, 604 of 651 (93%)
      urethroplasties performed had adequate data with a mean follow-up of 52 months.
      Overall urethral patency was 90.7% with failures occurring between 2 weeks and 77
      months postoperatively. The average time to recurrence was 11.7 months, with most
      patients with recurrence within 6 months (42/56; 75%). Multivariate regression
      identified Lichen sclerosus, iatrogenic, and infectious etiologies to be
      independently associated with stricture recurrence with hazard ratios (HR) (95%
      confidence interval) of 5.9 (2.1-16.5; p <= 0.001), 3.4 (1.2-10; p = 0.02), and
      7.3 (2.3-23.7; p <= 0.001), respectively. Strictures >=5cm recurred significantly
      more often (13.8% vs. 5.9%) with a HR 2.3 (1.2-4.5; p <= 0.01). Comorbidities,
      smoking, previous urethroplasty, stricture location and an age >=50 were not
      associated with recurrence. CONCLUSION: Urethroplasty in general is an excellent
      treatment for urethral stricture with patency rates approaching 91%. While
      recurrences occur over 6 years after surgery, most (75%) recur within the first 6
      months. Long segment strictures (>=5 cm), as well as Lichen sclerosus, infectious
      and iatrogenic etiologies, are associated with increased risk of recurrence.
      Limitations include the retrospective, single-centre nature of the study and the
      7% loss to follow-up due to the centre being a regional referral one.

PMID- 24940454
TI  - Incidence of infectious complications following transrectal ultrasound-guided
      prostate biopsy in Calgary, Alberta, Canada: A retrospective population-based
      analysis.
AB  - INTRODUCTION: We have seen an increased risk of infectious complications
      following transrectal ultrasound-guided prostate biopsy (TRUS-PB).
      Fluoroquinolone (FQ) antibiotics are common for prophylaxis prior to TRUS-PB. We
      evaluate whether increasing FQ resistance correlates with increased incidence of
      post-biopsy infectious complications at our institution. METHODS: We conducted a
      retrospective chart and electronic health record review on 927 patients who
      underwent TRUS-PB between January and July of 2012 in Calgary, Alberta, Canada.
      We prospectively collected the following variables: age, pre-biopsy prostate
      specific antigen, and date of biopsy. We documented presentation to an emergency
      department within 30 days of TRUS-PB for infectious and non-infectious
      complications. RESULTS: Of the 927 patients, 58 patients (6.3%) were admitted to
      the emergency department due to post-TRUS-PB complications within 30 days post
      biopsy. The most common infectious complications were sepsis in 21 patients
      (2.2%), followed by urinary tract infection (UTI) in 9 (0.9%), and prostatitis in
      4 (0.4%). We found that 83% of the septic episodes and 66.6% of the UTIs were
      attributed to ciprofloxacin resistant Escherichia coli (E. coli). The incidence
      of non-infectious complications was as follows: urinary retention in 12 (1.2%),
      hematuria in 9 (0.9%), and rectal bleeding in 8 (0.8%). CONCLUSION: Our results
      suggest an increased incidence of infectious complications caused by FQ resistant
      organisms following TRUS-PB. This finding could be attributed to increasing
      community resistance to ciprofloxacin. The current antimicrobial prophylactic
      regimen needs to be re-evaluated, and a novel approach may need to be considered.

PMID- 24940455
TI  - Tumour stage on re-staging transurethral resection predicts recurrence and
      progression-free survival of patients with high-risk non-muscle invasive bladder
      cancer.
AB  - INTRODUCTION: To identify patients who should be considered for early radical
      cystectomy, we evaluated the clinical and pathological variables affecting the
      outcome of patients with high-risk non-muscle invasive bladder cancer (NMIBC) who
      underwent re-staging transurethral resection (re-TUR). METHODS: We reviewed the
      clinical data of 453 patients treated for urothelial carcinoma between 2006 and
      2010. In total, 94 patients underwent re-TUR after their initial TUR. Of these,
      72 were not upstaged to muscle invasive disease and were therefore included in
      our study. RESULTS: On re-TUR, 31 patients had no residual tumour (T0) and 41
      patients had residual NMIBC. A statistically significant difference was noted
      between patients with pT0 and patients with residual NMIBC on re-TUR in regard to
      tumour recurrence and progression (39% vs. 83%, p < 0.001) (6% vs. 34%, p =
      0.005), respectively. On multivariate analysis, tumour stage on re-TUR and the
      regimen of intravesical bacillus Calmette-Guerin (BCG) therapy (induction vs.
      maintenance) remained independent predicting factors for recurrence-free survival
      (RFS) (p = 0.001, hazard ratio [HR]: 1.77), (p < 0.001 HR: 0.16) and progression
      free survival (PFS) (p = 0.014, HR: 2.11), (p = 0.008, HR: 0.097), respectively.
      CONCLUSIONS: The presence of T0 on re-TUR is associated with better RFS and PFS
      and could be a predictive factor for candidates for conservative management.
      Patients with persistent NMIBC on re-TUR require close follow-up and, in some
      cases, could be considered for early cystectomy. Maintenance intravesical BCG
      therapy can improve RFS and PFS in patients with high-risk NMIBC. This study is
      limited by its retrospective nature and the relatively small number of patients
      in the cohort.

PMID- 24940456
TI  - Does gender influence morbidity or mortality in the surgical treatment of renal
      masses?
AB  - INTRODUCTION: We determine the relationship between gender and surgical morbidity
      after radical nephrectomy (RN) and partial nephrectomy (PN) for renal masses on a
      population level. METHODS: We conducted a population-based, retrospective study
      using the Canadian Institute for Health Information Discharge Abstract Database.
      This included 20 286 RNs (82.5%) and 4292 PNs (17.5%) from April 1, 1998 to March
      31, 2008. Complications were identified by ICD-9 and 10 codes, and comorbidity
      was assessed with the Charlson Index. The association between gender and in
      hospital complication rates and mortality were examined using the Chi-square
      test, as well as with multivariable logistic regression, adjusting for
      explanatory variables including type of surgery, age, and comorbidity. RESULTS:
      Overall, men experienced a higher unadjusted complication rate than women (35.1%
      vs. 32.7%), as well as a higher unadjusted in-hospital mortality rate (1.46% vs.
      0.84%), respectively. Men also demonstrated significantly higher rates of
      cardiac, wound, nephrectomy-specific, and medical complications. Women
      experienced fewer complications than men after RN (p = 0.0002), but not after PN
      (p = 0.33). On multivariable logistic regression analysis, women had a lower
      overall complication rate (odds ratio [OR] 0.94, 95% confidence interval [CI]
      0.88-0.99), and a lower inhospital mortality rate (OR 0.64, 95% CI 0.49-0.83)
      after kidney surgery. CONCLUSIONS: In our population-based analysis, in-hospital
      morbidity after renal surgery was significantly lower for women. Further study is
      needed to determine if the observed effect is related to differences in surgical
      difficulty, perioperative care, or unmeasured confounders.

PMID- 24940457
TI  - Are stone analysis results different with repeated sampling?
AB  - INTRODUCTION: We assessed differences in results of stone analyses on subsequent
      sampling. METHODS: A retrospective review of patients with stone analyses at a
      tertiary stone centre between March 2006 and July 2012 was performed. All stones
      were analyzed at a centralized laboratory using infrared spectroscopy. Patients
      were grouped according to the first predominant stone type on record, as defined
      by the predominant stone component of at least 60%. Stone groups included calcium
      oxalate (CaOx), calcium phosphate (CaP), uric acid (UA), cystine, struvite, mixed
      CaOx-CaP and mixed CaOx-UA. All patients had a full metabolic stone workup.
      RESULTS: Of the 303 patients with stone analyses, 118 (38.9%) patients had
      multiple stone analyses. The mean age was 53.4 +/- 15.1 years, and 87 (73.7%)
      were males. Of the 118, the initial stone analysis showed 43 CaOx, 38 CaP, 21 UA,
      4 CaOx-CaP, 2 CaOx-UA, 6 cystine, and 4 struvite. There was a different stone
      composition in 25 (21.2%) patients with a median time delay of 64.5 days.
      Different compositions were found in 7 CaOx (to 3 CaP, 2 CaOx-CaP, and 2 UA), 5
      CaP (to 3 CaOx and 2 CaOx-CaP), 3 UA (to 3 CaOx), 4 CaOx-CaP (to 2CaOx, 1 UA and
      1 CaP), 2 CaOx-UA (to 2 CaOx) and 4 struvite (to 3 CaP and 1 UA). CONCLUSIONS:
      Stone composition was different in 21.2% of patients on subsequent analyses.

PMID- 24940458
TI  - Colonic perforation during percutaneous nephrolithotomy: An 18-year experience.
AB  - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for
      large, extracorporeal lithotripsy failure stones and those in the inferior calyx.
      Despite the development of new techniques and the increasing experience in recent
      decades, complications may still occur. Colonic perforation is one of the most
      dangerous and rare complications of PCNL, which may lead to peritonitis and
      sepsis. We present our 18-year experience on the diagnosis and management of
      colonic perforation during PCNL. METHODS: We retrospectively reviewed the data of
      5260 PCNL procedures performed between May1995 and August 2013. Preoperative and
      operative factors, such as age, sex, history of previous ipsilateral stone
      intervention, stone side, stone location, site of skin puncture and punctured
      calyx, were reviewed in patients with colonic injury. RESULTS: Colonic
      perforation was found in 11 patients (5 males and 6 females) and the mean age was
      40.4 +/- 22.2 years (range: 4 to 71). All injuries were retroperitoneal. The left
      side was affected in 5 patients and the right side was injured in 6 cases.
      Conservative management was the treatment planned for all patients. It included
      withdrawal of the nephrostomy tube outside the kidney to the colon as a
      percutaneous colostomy, insertion of a double-J ureteral stent, intravenous broad
      spectrum antibiotics, bowel rest and total parenteral nutrition. Under this
      conservative management, complete healing of the colon was achieved in all
      patients. CONCLUSION: Early diagnosis and conservative management of colonic
      perforation can minimize patient morbidity and mortality and result in excellent
      healing of the fistulous tract without any serious complications.

PMID- 24940459
TI  - Prostate cancer detection by prostate-specific antigen-based screening in the
      Japanese Hiroshima area shows early stage, low-grade, and low rate of cancer
      specific death compared with clinical detection.
AB  - INTRODUCTION: We investigate the effectiveness of prostate-specific antigen (PSA)
      screening for prostate cancer. We compare the characteristics of 2 sets of
      patients: (1) those in whom prostate cancer was detected via PSA screening (the
      PS group) and (2) those in whom prostate cancer was detected at the outpatient
      office (the non-PS group). METHODS: Between 2002 and 2010, prostate cancer was
      detected in 315 patients by PSA screening. Their age, initial PSA level,
      pathological findings in biopsy specimens, clinical stage, and prognosis were
      compared with those of 497 prostate cancer patients diagnosed at the outpatient
      office of the Department of Urology, Hiroshima University, in the same period.
      RESULTS: The rates of patients with initial PSA higher than 50 ng/mL, with a
      Gleason score of 8 or higher, and with clinical stage D were significantly lower
      in the PS group than those in the non-PS group. The 5-year overall survival and
      cancer-specific survival in the PS group was 91.3% and 98.2%, respectively; these
      results were significantly better than those in the non-PS group (86.4%, p =
      0.0178, and 94.9%, p = 0.0112, respectively). A Cox hazard analysis showed that
      PSA screening was an independent predictive factor for cancer-specific survival.
      CONCLUSIONS: Although our study is limited by its retrospective nature and small
      size, the present data indicate that prostate cancer detected in the PS group
      showed earlier stage, lower grade, and better prognosis than in the non-PS group.

PMID- 24940460
TI  - Survival analysis of patients with biochemical relapse after radical
      prostatectomy treated with androgen deprivation: Castration-resistance
      influential factors.
AB  - INTRODUCTION: We evaluate the prognosis of patients with biochemical recurrence
      (BCR) treated with androgen deprivation therapy (ADT) and to determine the
      influential factors to castration resistance (CR) and death. METHODS: From a
      series of 1310 patients with T1-T2 prostate cancer treated with radical
      prostatectomy between 1989 and 2012, 371 had BCR. Patients with lymph node
      involvement were excluded. We analyzed only the 159 treated with salvage ADT. At
      the end of the study, 77 (48%) had developed CR. RESULTS: The median follow-up to
      CR was 9.2 years. The CR-resistant free survival (RFS) was 76 +/- 3%, 62 +/- 3%
      and 43 +/- 9% in 5, 10 and 15 years, respectively. The RFS median time was 14
      years. In the multivariate study, the prostate-specific antigen (PSA) doubling
      time (PSA-DT) was <6 months (p = 0.01) (hazard ratio [HR] 3; 95% confidence
      interval [CI] 1.4-6.8, p = 0.007); seminal vesicle involvement (HR 3.1; 95% CI
      1.5-6.2, p = 0.01) and PSA velocity in ng/mL/year (HR 1.3; 95% CI 1.1-1.5, p =
      0.002) with better cut-off points of 0.84 ng/mL/year (p = 0.04) (HR 4; 95% CI 1.7
      9.4, p = 0.001) were influential variables. Specific survival (SS) at 5, 10 and
      15 years since surgery was 96 +/- 1, 85 +/- 2 and 76 +/- 4, respectively. The
      time of CR to death was 30 +/- 6% at 5 years, with the median at 3.2 years. In
      the multivariate only Ki 67 (HR 1.04; 95% CI 1.005-1.08, p = 0.02) had an
      independent influence. CONCLUSIONS: In BCR patients treated with ADT, the median
      to CR was 14 years. PSA-DT <6 months, PSA velocity (ng/mL/year) and seminal
      vesicle involvement were influential variables. From the CR, the median time to
      death was 3.2 years. Ki-67 marker was an independent influence.

PMID- 24940461
TI  - Predictors of Gleason score upgrading in patients with prostate biopsy Gleason
      score <=6.
AB  - INTRODUCTION: The discrepancy between prostate biopsy and prostatectomy Gleason
      scores is common. We investigate the predictive value of prostate biopsy features
      for predicting Gleason score (GS) upgrading in patients with biopsy Gleason
      scores <=6 who underwent radical retropubic prostatectomy (RRP). Our aim was to
      determine predictors of GS upgrading and to offer guidance to clinicians in
      determining the therapeutic option. METHODS: We performed a retrospective study
      of patients who underwent RRP for clinically localized prostate cancer at 2 major
      centres between January 2007 and March 2013. All patients with either abnormal
      digital examination or elevated prostate-specific antigen at screening underwent
      transrectal ultrasound-guided prostate biopsy. Variables were evaluated among the
      patients with and without GS upgrading. Our study limitations include its
      retrospective design, the fact that all subjects were Turkish and the fact that
      we had a small sample size. RESULTS: In total, 321 men had GS <=6 on prostate
      biopsy. Of these, 190 (59.2%) had GS<=6 concordance and 131 (40.8%) had GS
      upgrading from <=6 on biopsy to 7 or higher at the time of the prostatectomy.
      Independent predictors of pathological upgrading were prostate volume <40 cc (p <
      0.001), maximum percent of cancer in any core (p = 0.011), and >1 core positive
      for cancer (p < 0.001). CONCLUSIONS: When obtaining an extended-core biopsy
      scheme, patients with small prostates (<=40 cc), greater than 1 core positive for
      cancer, and an increased burden of cancer are associated with increased risk of
      GS upgrading. Patients with GS <=6 on biopsy with these pathological parameters
      should be carefully counselled on treatment decisions.

PMID- 24940462
TI  - Bladder tumour antigen (BTA stat) test compared to the urine cytology in the
      diagnosis of bladder cancer: A meta-analysis.
AB  - INTRODUCTION: We evaluate the diagnostic value of bladder tumour antigen (BTA
      stat) tests compared with urine cytology test in detecting bladder cancer.
      METHODS: We searched public databases including PubMed, MEDLINE Springer,
      Elsevier Science Direct, Cochrane Library and Google Scholar before December
      2012. To collect relevant data of BTA stat tests and urine cytology tests in
      patients with bladder cancer, we studied meta-analyses of sensitivity,
      specificity, positive likelihood ratio (LR), negative LR and diagnostic odds
      ratios (DOR) of BTA stat tests and cytology tests from published studies. We
      applied the software of Rev. Man 5.1 and Stata 11.0 to the meta-analysis.
      RESULTS: A total of 13 separate studies consisting of 3462 patients with bladder
      cancer were considered in the meta-analysis. We found that the BTA stat test had
      a higher sensitivity than the urine cytology test (0.67, 95% confidence interval
      [CI] 0.64 to 0.69 vs. 0.43, 95% CI 0.40 to 0.46), but the specificity, positive
      LR, negative LR, DOR, the area under the curve (AUC) and Q index of the BTA stat
      test were lower compared with the urine cytology test. The results of the Egger's
      linear regression test showed no publication bias (p > 0.05). CONCLUSIONS:
      Specificity, positive LR, negative LR, DOR, the AUC and the Q index of the urine
      cytology test may be superior to the BTA stat test, but the BTA stat test has
      greater sensitivity than the urine cytology test.

PMID- 24940463
TI  - Synchronous primary malignancies of the male urogenital tract.
AB  - The finding of prostate cancer after a cystoprostatectomy for a bladder tumour
      can occur in up to 70% of cases. The incidence of prostate cancer in patients
      with a bladder tumour is 18 times higher than in the general population;
      moreover, the incidence of bladder cancer in patients with prostate cancer is 19
      times higher than in the general population. This association can be explained by
      the common embryological origin of these organs, with molecular similarities.
      Other similarities between these two cancers are noted. They are multifocal and
      may be secondary to urinary stasis. However, this association does not seem
      responsible for an increased risk of progression of both diseases. The prognosis
      is related to the extension of each cancer. The stage and grade of bladder cancer
      are, in terms of prognosis, greater than those of prostate cancer. Most often,
      this is insignificant prostate cancer. Despite this, the prostate-specific
      antigen test should be administered to monitor patients after cystoprostatectomy.

PMID- 24940464
TI  - A critical analysis of testosterone supplementation therapy and cardiovascular
      risk in elderly men.

PMID- 24940465
TI  - Massive stone burden in an ileocecal pouch: A preventable condition?
AB  - The challenges of transition from the pediatric to the adult setting have been
      reported. We describe a case of massive stone burden in the ileocecal pouch of a
      patient lost to follow-up after his transfer from a pediatric to an adult
      institution. Although we successfully managed the patient and retrieved the pouch
      stones without any complications, several surgical complications may occur in a
      patient with a history of extensive abdominal surgery and bladder exstrophy. This
      patient's late complication might have been prevented with a more efficient
      transfer from a pediatric to an adult institution. 

PMID- 24940466
TI  - Isolated anterior urethral recurrence of prostatic adenocarcinoma.
AB  - Isolated anterior urethral metastases from prostate cancer are rare. The
      pathogenesis of this form of loco-regional recurrence may be related to spread by
      instrumentation-induced implantation and could potentially then be associated
      with a better prognosis than metastatic disease secondary to a more malignant
      phenotype. We report a case of a 68-year-old man with high-risk prostate cancer,
      diagnosed at transurethral resection of prostate, who was originally treated with
      combination external beam radiotherapy and hormonal therapy. He re-presented 4
      years after his original diagnosis with recurrent gross hematuria and
      cystourethroscopic biopsies of anterior urethral polyps revealing isolated
      recurrent prostatic adenocarcinoma. We present our this case and review the
      literature. 

PMID- 24940467
TI  - Urethral squamous cell papilloma: Case report and literature review.
AB  - Lesions around the urethral meatus in women are common. The differential
      diagnosis for these lesions is extensive and includes urethral caruncle, urethral
      prolapse, urethral diverticulum, periurethral gland abscesses and, of most
      concern, urethral carcinoma. Non-invasive squamous lesions of the urethra are
      rare and their clinical significance is uncertain. We present a case of a
      urethral squamous papilloma at the urethral meatus in a premenopausal woman
      causing significant symptoms. 

PMID- 24940468
TI  - Laparoscopic dissection of the intramural ureter to repair a complete transection
      of the distal ureter: Initial experience with a new minimally invasive technique
      that preserves the anatomy of the urinary tract.
AB  - We report 2 patients with ureteral injury after a simple total laparoscopic
      hysterectomy for uterine myoma with a complete resection of the distal ureter.
      One patient had unilateral injury and the other 2 patients had bilateral injury.
      The surgical laparoscopic repair procedure was carried out 3 to 5 days after the
      injury. Surgery involved intramural dissection of the distal ureteral stump to
      expose at least 1 cm of the ureter, percutaneous ureteral stent placement,
      elimination of tension between the proximal ureter and the dissected distal
      stump, end-to-end anastomosis, and reinsertion of the distal ureter into the
      bladder muscle layer, which was previously dissected for the anastomosis. 

PMID- 24940469
TI  - Isolated rupture of the superficial vein of the penis.
AB  - Penile emergencies are rare but when they do occur, prompt diagnosis and
      treatment are warranted. Emergent conditions of the male genitalia are mainly
      traumatic, vascular or infectious. Penile emergencies are usually caused by
      trauma to the penis, during sexual intercourse or manipulation of an erect penis
      during masturbation. One of the traumatic vascular penile emergencies is
      superficial penile dorsal vein rupture. This is a rare condition, with just a few
      reported cases. It is usually taken into differential diagnosis with the other
      acute penile injuries that present, such as acute penile edema or ecchymosis. We
      report a case of 59-year-old male with a superficial penile dorsal vein rupture
      which occurred during manipulation of the erect penis. 

PMID- 24940470
TI  - Largest pheochromocytoma reported in Canada: A case study and literature review.
AB  - Most giant pheochromocytomas do not present with classic symptoms, as documented
      by published case reports. Given this, clinicians have to consider a wide
      differential diagnosis for any retroperitoneal mass and perform screening tests
      to rule out a pheochromocytoma. We describe the largest pheochromocytoma reported
      in Canada, where the patient presented with a palpable abdominal mass and
      dyspnea. The 19 * 18 * 12-cm right retroperitoneal mass was biochemically active
      and was radiologically and pathologically consistent with a giant
      pheochromocytoma. We present this case and review the relevant current
      literature. 

PMID- 24940471
TI  - Sildenafil can induce the onset of a cluster headache bout.
AB  - About 25% of patients who are prescribed sildenafil, the phosphodiesterase type 5
      (PDE-5) inhibitor, for erectile dysfunction (ED) experience headaches. These
      migraine effects are well-described, including cluster headaches. We report the
      case of a man who experienced a cluster headache attack following each of 2
      sildenafil doses. His symptoms were resolved by adding naproxen to his treatment
      regimen and changing his ED treatment from 50 mg of sildenafil to 5 mg of
      vardenafil. To our knowledge, no study has reported cluster headaches triggered
      by the less commonly used PDE-5 inhibitors, namely vardenafil and tadalafil.
      Urologists should be cautious in prescribing sildenafil to patients with ED and
      with a history of cluster headaches. In these patients, they should consider
      prescribing low-dose vardenafil or tadalafil instead. Failure to recognize
      sildenafil risks could result in unnecessary headache bouts in patients with a
      history of cluster headaches. 

PMID- 24940472
TI  - Bladder incarceration with perforation in scrotal herniation: A case report.
AB  - Inguinoscrotal hernias containing urinary bladder are very rare. There are only a
      few cases described with perforation in the scrotum. This illness is a severe and
      should be kept in mind with any patient complaining of a scrotal hernia. We
      report a case of bladder perforation caused by inguinoscrotal hernia with
      incarceration and severe sepsis in a 93-year-old male. A computed tomography scan
      with excretory phase was used to diagnose the disease. A laparotomy with partial
      bladder resection and herniotomy were performed. Our patient recovered well from
      surgery. Ten days after surgery, a cystography was performed showing no
      extravasation. 

PMID- 24940473
TI  - [Not Available].

PMID- 24940474
TI  - [Not Available].

PMID- 24940476
TI  - Allergic diseases and asthma: a global public health concern and a call to
      action.

PMID- 24940475
TI  - Immunological cross-reactivity between olive and grass pollen: implication of
      major and minor allergens.
AB  - BACKGROUND: Grasses and olive trees are the most common sources of allergenic
      pollen worldwide. Although they share some allergens, there are few studies
      analyzing the in vitro cross-reactivity between them. The aim was to define the
      cross-reactivity between Olea europaea and Phleum pratense using well
      characterized sera of allergic children from Madrid, Spain. METHODS: 66 patients
      (mean age 10.32+/-4.07 years) were included in the study. All suffered from
      rhinoconjuntivitis and/or asthma and had a positive skin test and/or specific IgE
      determination to olive and grass pollen. Serum sIgE to individual allergens was
      conducted and sIgE against different grass species and olive was also determined
      by ELISA. Inhibition assays were performed using two serum sources, containing,
      or not, sIgE to minor allergens. Mass spectrometry analysis was performed in both
      extracts. RESULTS: 59/66 (89.39%) children had a positive sIgE determination by
      ELISA to grasses and 57/66 (86.36%) to olive pollen. There was no significant
      correlation between sIgE levels to grass and olive. Inhibition assays
      demonstrated no cross-reactivity between P. pratense and olive pollen when using
      the pool containing mainly sIgE to major allergens, whereas minimal to moderate
      cross-reactivity was detected when the serum contained high sIgE titers to minor
      allergens. Proteomic analyses revealed the presence of 42 common proteins in
      grasses and olive pollens. CONCLUSION: No in vitro cross-reactivity was observed
      when sIgE was mainly directed to major allergens. In our population,
      sensitization to olive and grasses is not due to cross-reactivity. The
      contribution of the major allergens seems to be determinant.

PMID- 24940477
TI  - Pluripotent muse cells derived from human adipose tissue: a new perspective on
      regenerative medicine and cell therapy.
AB  - In 2010, Multilineage Differentiating Stress Enduring (Muse) cells were
      introduced to the scientific community, offering potential resolution to the
      issue of teratoma formation that plagues both embryonic stem (ES) and induced
      pluripotent (iPS) stem cells. Isolated from human bone marrow, dermal
      fibroblasts, adipose tissue and commercially available adipose stem cells (ASCs)
      under severe cellular stress conditions, Muse cells self-renew in a controlled
      manner and do not form teratomas when injected into immune-deficient mice.
      Furthermore, Muse cells express classic pluripotency markers and differentiate
      into cells from the three embryonic germ layers both spontaneously and under
      media-specific induction. When transplanted in vivo, Muse cells contribute to
      tissue generation and repair. This review delves into the aspects of Muse cells
      that set them apart from ES, iPS, and various reported adult pluripotent stem
      cell lines, with specific emphasis on Muse cells derived from adipose tissue
      (Muse-AT), and their potential to revolutionize the field of regenerative
      medicine and stem cell therapy. 

PMID- 24940478
TI  - Immediate versus delayed integrated point-of-care-ultrasonography to manage acute
      dyspnea in the emergency department.
AB  - BACKGROUND: Dyspnea is one of the most frequent complaints in the Emergency
      Department. Thoracic ultrasound should help to differentiate cardiogenic from non
      cardiogenic causes of dyspnea. We evaluated whether the diagnostic accuracy can
      be improved by adding a point-of-care-ultrasonography (POC-US) to routine exams
      and if an early use of this technique produces any advantage. METHODS: One
      hundred sixty-eight patients were enrolled and randomized in two groups: Group 1
      received an immediate POC-US in addition to routine laboratory and instrumental
      tests; group 2 received an ultrasound scan within 1 h from the admission to the
      Emergency Department. The concordance between initial and final diagnosis and the
      percentage of wrong diagnosis in the two groups were evaluated. Mortality, days
      of hospitalization in Emergency Medicine department and transfers to other wards
      were compared. Sensitivity and specificity of the routine protocol and the one
      including ultrasonography for the diagnosis of the causes of dyspnea were also
      analyzed. RESULTS: Eighty-eight patients were randomized in group 1 and 80 in
      group 2. The concordance rate between initial and final diagnoses was
      significantly different (0.94 in group 1 vs. 0.22 in group 2, p < 0.005). The
      percentage of wrong initial diagnosis was 5% in group 1 and 50% in group 2 (p <
      0.0001). CONCLUSIONS: Adding POC-US to routine exams improves the diagnostic
      accuracy of dyspnea and reduces errors in the Emergency Department.

PMID- 24940481
TI  - News from the editors of Fluids and Barriers of the CNS.
AB  - This editorial announces a new affiliation between Fluids and Barriers of the CNS
      (FBCNS) and the International Brain Barriers Society (IBBS) with mutual benefits
      to the journal and to society members. This is a natural progression from the
      appointment of two new Co-Editors in Chief: Professor Lester Drewes and Professor
      Richard Keep in 2013. FBCNS provides a unique and specialist platform for the
      publication of research in the expanding fields of brain barriers and brain fluid
      systems in both health and disease. 

PMID- 24940479
TI  - Facioscapulohumeral dystrophy: the path to consensus on pathophysiology.
AB  - Although the pathophysiology of facioscapulohumeral dystrophy (FSHD) has been
      controversial over the last decades, progress in recent years has led to a model
      that incorporates these decades of findings and is gaining general acceptance in
      the FSHD research community. Here we review how the contributions from many labs
      over many years led to an understanding of a fundamentally new mechanism of human
      disease. FSHD is caused by inefficient repeat-mediated epigenetic repression of
      the D4Z4 macrosatellite repeat array on chromosome 4, resulting in the variegated
      expression of the DUX4 retrogene, encoding a double-homeobox transcription
      factor, in skeletal muscle. Normally expressed in the testis and epigenetically
      repressed in somatic tissues, DUX4 expression in skeletal muscle induces
      expression of many germline, stem cell, and other genes that might account for
      the pathophysiology of FSHD. Although some disagreements regarding the details of
      mechanisms remain in the field, the coalescing agreement on a central model of
      pathophysiology represents a pivot-point in FSHD research, transitioning the
      field from discovery-oriented studies to translational studies aimed at
      developing therapies based on a sound model of disease pathophysiology. 

PMID- 24940482
TI  - Intratumoral injection of cisplatin in various concentrations of ethanol for
      cisplatin-resistant lung tumors.
AB  - Cisplatin [cis-diammineplatinum dichloride (DDP)] resistance is a major
      limitation in the treatment of lung cancer. We previously demonstrated that DDP
      dissolved in 5% ethanol (5% ethanol-DDP) injected intratumorally was able to
      eradicate DDP-resistant lung tumors and prolong survival, as 5% ethanol improved
      DDP delivery to the tumor. The present study aimed to investigate the efficacy of
      DDP in various concentrations of ethanol and determine the optimal ethanol
      concentration in which DDP exhibits optimal efficacy in reducing tumor volume and
      prolonging survival. The efficiency of DDP dissolved in 2, 5, 10, 20 and 50%
      ethanol (v/v) in DDP-resistant A549/DDP lung tumor-bearing Balb/C nude mice was
      investigated. Tumor growth and survival were evaluated in all the treatment
      groups. Microvessel density in xenograft tumor tissues was measured by
      immunohistochemistry. Our results revealed that 5% ethanol-DDP exhibited the
      highest efficiency in reducing tumor volume and prolonging survival among all the
      investigated ethanol-DDP combinations. We found that 5% ethanol-DDP produced the
      most significant inhibition of tumor angiogenesis among all the remaining ethanol
      DDP combinations, while treatment with ethanol alone increased tumor
      angiogenesis. In conclusion, 5% ethanol-DDP produced the strongest tumor growth
      inhibition and longest survival among all the investigated ethanol-DDP
      combinations, possibly providing a novel therapeutic strategy for improving the
      survival of patients with DDP-resistant lung cancer. The potent inhibition of
      tumor angiogenesis by 5% ethanol-DDP may be one of the mechanisms underlying its
      superior efficiency.

PMID- 24940483
TI  - Successful treatment of rectal cancer with perineal invasion: Three case reports.
AB  - Rectal cancer occasionally invades adjacent organs. However, rectal cancer with
      perineal invasion is uncommon and difficult to treat. Locally advanced colorectal
      cancer may be clinically treated with neoadjuvant therapy, followed by en bloc
      resection. Skin invasion may lead to tumor dissemination via cutaneous blood flow
      and lymphatic routes. There is currently no firm evidence regarding the treatment
      of these significantly advanced rectal cancers. In this study, we report 3 cases
      of rectal cancer with perineal invasion, successfully managed by multimodality
      treatment. Case 1 is a 52-year-old man with rectal cancer that had invaded the
      perineum; case 2 is a 38-year-old man with rectal cancer infiltrating the
      perineal skin and liver metastasis; and case 3 is a 50-year-old woman with rectal
      cancer and perineal invasion. All the cases were treated with radical excision.
      No severe complications were observed in the perioperative period. Case 2, in
      particular, was confirmed to remain alive 5 years after the surgery. Our
      experience suggests that multimodality treatment, including extended radical
      surgery, may be a feasible approach to the treatment of rectal cancer with
      perineal skin invasion.

PMID- 24940480
TI  - Finding of widespread viral and bacterial revolution dsDNA translocation motors
      distinct from rotation motors by channel chirality and size.
AB  - BACKGROUND: Double-stranded DNA translocation is ubiquitous in living systems.
      Cell mitosis, bacterial binary fission, DNA replication or repair, homologous
      recombination, Holliday junction resolution, viral genome packaging and cell
      entry all involve biomotor-driven dsDNA translocation. Previously, biomotors have
      been primarily classified into linear and rotational motors. We recently
      discovered a third class of dsDNA translocation motors in Phi29 utilizing
      revolution mechanism without rotation. Analogically, the Earth rotates around its
      own axis every 24 hours, but revolves around the Sun every 365 days. RESULTS:
      Single-channel DNA translocation conductance assay combined with structure
      inspections of motor channels on bacteriophages P22, SPP1, HK97, T7, T4, Phi29,
      and other dsDNA translocation motors such as bacterial FtsK and eukaryotic
      mimiviruses or vaccinia viruses showed that revolution motor is widespread. The
      force generation mechanism for revolution motors is elucidated. Revolution motors
      can be differentiated from rotation motors by their channel size and chirality.
      Crystal structure inspection revealed that revolution motors commonly exhibit
      channel diameters larger than 3 nm, while rotation motors that rotate around one
      of the two separated DNA strands feature a diameter smaller than 2 nm. Phi29
      revolution motor translocated double- and tetra-stranded DNA that occupied 32%
      and 64% of the narrowest channel cross-section, respectively, evidencing that
      revolution motors exhibit channel diameters significantly wider than the dsDNA.
      Left-handed oriented channels found in revolution motors drive the right-handed
      dsDNA via anti-chiral interaction, while right-handed channels observed in
      rotation motors drive the right-handed dsDNA via parallel threads. Tethering both
      the motor and the dsDNA distal-end of the revolution motor does not block DNA
      packaging, indicating that no rotation is required for motors of dsDNA phages,
      while a small-angle left-handed twist of dsDNA that is aligned with the channel
      could occur due to the conformational change of the phage motor channels from a
      left-handed configuration for DNA entry to a right-handed configuration for DNA
      ejection for host cell infection. CONCLUSIONS: The revolution motor is widespread
      among biological systems, and can be distinguished from rotation motors by
      channel size and chirality. The revolution mechanism renders dsDNA void of
      coiling and torque during translocation of the lengthy helical chromosome, thus
      resulting in more efficient motor energy conversion.

PMID- 24940484
TI  - Association between vascular endothelial growth factor gene polymorphisms and
      bladder cancer risk.
AB  - Vascular endothelial growth factor (VEGF) gene polymorphisms are associated with
      susceptibility to a number of cancers. The present case-controlled study aimed to
      investigate the correlation between VEGF gene polymorphisms and the risk of
      bladder cancer. The effects of VEGF polymorphisms were investigated in patients
      with bladder cancer and healthy controls in our hospital between May, 2008 and
      May, 2013. Peripheral blood samples were obtained from 480 patients with bladder
      cancer and 420 healthy controls. The polymerase chain reaction-restriction
      fragment length polymorphism technique was used to detect three VEGF gene
      polymorphisms (rs3025039 C/T, rs833052 C/A and rs1570360 G/A) in these subjects.
      The genotype and allele frequencies were also investigated in order to determine
      their association with stage, grade and histological type of bladder cancer, as
      well as smoking status. Our results suggested that the frequency of the rs833052
      AA genotype was significantly higher in patients with bladder cancer [odds ratio
      (OR)=1.75; 95% confidence interval (CI): 1.05-2.92; P=0.03] compared to that in
      healthy controls. There was no significant correlation between the rs833052 AA
      genotype and bladder cancer stage, grade or histological type, whereas smoking
      was identified as a risk factor for bladder cancer in the included patients
      (OR=1.48; 95% CI: 1.13-1.93; P=0.004). The rs3025039 and rs1570360 gene
      polymorphisms were not found to be correlated with the risk of bladder cancer or
      its progression. In conclusion, our results suggested that the VEGF rs833052 C/A
      polymorphism may be associated with a modest increase in the risk of bladder
      cancer in Chinese individuals.

PMID- 24940485
TI  - Association of serum hemoglobin A1c, C-peptide and insulin-like growth factor-1
      levels with the occurrence and development of lung cancer.
AB  - The present study aimed to investigate the correlation of the of hemoglobin A1c
      (HbA1c), C-peptide and insulin-like growth factor-1 (IGF-1) levels with the
      development and progression of lung cancer. The serum HbA1c, C-peptide and IGF-1
      levels were measured and compared between 80 lung cancer patients and 80 healthy
      controls; furthermore, their correlation with histopathological type and tumor
      stage was analyzed in the 80 lung cancer patients. Our results suggested that the
      levels of HbA1c, C-peptide and IGF-1 were significantly increased in patients
      with lung cancer compared to those in the control group (P<0.05). In addition,
      the levels of C-peptide and IGF-1 were significantly higher in the small-cell
      lung cancer group (n=18), the stage III-IV (n=55) group and the lung cancer with
      diabetes mellitus group (n=43) compared to those in the non-small-cell lung
      cancer group (n=62), the stage I-II lung cancer group (n=25) and the lung cancer
      without diabetes group (n=37), respectively (P<0.05). Thus, the present study
      suggests that the increased serum HbA1c, C-peptide and IGF-1 levels are
      significantly correlated with the development and progression of lung cancer.

PMID- 24940486
TI  - Prognostic significance of the co-overexpression of fibroblast growth factor
      receptors 1, 2 and 4 in gastric cancer.
AB  - The overexpression of fibroblast growth factor receptor (FGFR) 2 is an
      established prognostic factor and treatment target in gastric cancer. However,
      the roles of other FGFRs have not been fully elucidated. In this study, we
      investigated the correlations of the expression of FGFR1-4 with
      clinicopathological characteristics and outcomes in gastric cancer. Tumor samples
      were obtained from 222 patients with gastric adenocarcinoma who underwent
      gastrectomy between 2003 and 2007. The expression of each FGFR was measured in
      the tumors by immunohistochemical analysis. The overexpression of FGFR1, FGFR2 or
      FGFR4 was found to be significantly associated with tumor progression, including
      depth of invasion, lymph node metastasis, pathological stage and distant
      metastasis or recurrent disease. Patients exhibiting overexpression of FGFR1,
      FGFR2 or FGFR4 had a significantly poorer disease-specific survival (DSS;
      P<0.001, P=0.008 and P<0.001, respectively). Moreover, the co-overexpression of
      all three FGFRs was significantly associated with a poorer DSS compared to the
      expression of none or only one of the FGFRs (P<0.001 and P=0.001, respectively)
      and it was found to be an independent prognostic factor (HR=1.71, 95% CI: 1.02
      2.85, P=0.041). In conclusion, high expression of FGFR1, FGFR2 or FGFR4 was
      associated with tumor progression and poor survival in patients with gastric
      cancer. Similar to FGFR2, FGFR1 and FGFR4 may be considered as prognostic factors
      and treatment targets in gastric cancer.

PMID- 24940487
TI  - Comparison of outcomes between squamous cell carcinoma and adenocarcinoma in
      patients with surgically treated stage I-II cervical cancer.
AB  - To improve our understanding of cervical adenocarcinoma (AD) and evaluate the
      clinical and pathological variables affecting its prognosis, we retrospectively
      reviewed the medical records of 455 patients with cervical cancer [International
      Federation of Gynecology and Obstetrics stage I/II; 91 cases with AD and 364 with
      squamous cell carcinoma (SCC)] who underwent surgery at our hospital between
      January, 1995 and August, 2012 and compared the characteristics and prognoses
      between AD and SCC cases, including age, clinical stage, histological type, lymph
      node metastasis, lymphovascular space invasion (LVSI), cervical stromal invasion,
      parametrial invasion, vaginal invasion, corpus invasion, ovarian metastasis and
      tumor diameter. We used Cox regression analysis to determine independent
      prognostic factors. AD was found to have a significantly poorer prognosis in all
      the patients (P=0.001), stage I patients (P=0.001) and stage IB patients
      (P<0.05). The prognosis did not differ in patients who did not require
      postoperative treatment; however, patients who received postoperative treatment
      exhibited a significantly poorer prognosis (P<0.05). Patients with AD who
      received postoperative irradiation alone had a significantly poorer prognosis
      (P<0.05). The multivariate analysis identified LVSI (P=0.008), stromal invasion
      (P=0.024) and ovarian metastasis (P=0.032) as independent predictors of shorter
      survival. AD was associated with a worse prognosis compared to SCC in patients
      with stage IB disease, particularly in those who required postoperative
      treatment. Such patients may benefit from individualized postoperative treatments
      that differ from those applied for SCC.

PMID- 24940488
TI  - Correlation between positron emission tomography findings and glucose transporter
      1, 3 and L-type amino acid transporter 1 mRNA expression in primary central
      nervous system lymphomas.
AB  - Primary central nervous system lymphoma (PCNSL) is an aggressive form of non
      Hodgkin lymphoma with a poor prognosis. [18F] 2-fluoro-2-deoxy-D-glucose (FDG)
      and L-(methyl-11C)-methionine (MET) are the most widely used tracers in
      oncological positron emission tomography studies for PCNSL and commonly identify
      hypermetabolic lesions through increased uptake of FDG and MET. However, the
      mechanisms underlying the uptake of FDG and MET in PCNSL have not been clearly
      determined. The present study aimed to investigate the mRNA expression levels of
      glucose transporter (GLUT)1, GLUT3 and L-type amino acid transporter 1 (LAT1) in
      resected PCNSL specimens, in order to identify whether these transporters are
      associated with the increased uptake of FDG and MET. A total of 7 patients
      diagnosed with PCNSL were investigated. The uptake of FDG and MET by the tumors
      was evaluated based on the maximum standardized uptake value (SUVmax). The
      quantity of GLUT1, GLUT3 and LAT1 mRNA in the PCNSL specimens was measured to
      determine whether GLUT1, GLUT3 and/or LAT1 are involved in the increased uptake
      of FDG and MET in PCNSL. Furthermore, microvessel density (MVD) and cell density
      (CD) were measured in all the cases. Our results indicated that the expression of
      GLUT3, but not GLUT1, was significantly correlated with FDG SUVmax and the
      expression of LAT1 was significantly correlated with MET SUVmax. However, neither
      MVD nor CD were found to be significantly associated with the uptake of FDG and
      MET. GLUT3 was identified as a key determinant of FDG accumulation, whereas LAT1
      was a key determinant of MET accumulation in PCNSL. Therefore, GLUT3 and LAT1 may
      represent potential targets for the future development of novel therapeutic
      agents for PCNSL.

PMID- 24940489
TI  - Laparoscopic radical gastrectomy versus traditional open surgery in elderly
      patients with gastric cancer: Benefits and complications.
AB  - This study was conducted to compare the therapeutic effect and complications of
      laparoscopic radical gastrectomy (LRG) with those of traditional open surgery in
      elderly patients with gastric cancer (GC). We conducted a retrospective
      comparison of therapeutic efficacy and complications between elderly patients
      with GC (defined as those aged >=70 years) who received laparoscopic gastrectomy
      and those who underwent gastrectomy by open surgery. A total of 108 patients who
      either underwent laparoscopic surgery (n=54) or traditional open surgery (n=54)
      at the General Hospital of Lanzhou Military Region between June, 2008 and March,
      2009 were analyzed. Compared to traditional open surgery, LRG exhibited several
      advantages, such as being less invasive, with less intraoperative blood loss,
      shorter bedbound time, less intubation time, low frequency of fever, less time to
      normal diet, shorter hospital stay and a low overall incidence of complications.
      No significant difference was observed between laparoscopic and open surgery in
      terms of operative time and number of lymph nodes dissected. The 3-year cancer
      recurrence and mortality rates were similar in the two groups. In conclusion, LRG
      is a safe and effective procedure for the management of GC in elderly patients
      and was found to be superior to traditional open surgery regarding the short-term
      curative effect. Therefore, LRG represents a feasible and safe surgical approach
      for elderly patients with GC.

PMID- 24940490
TI  - Misjudgement of gefitinib efficacy in patients with central non-small-cell lung
      cancer due to obstructive atelectasis caused by stereotactic radiotherapy.
AB  - Stereotactic body radiation therapy (SBRT) has been reported to be safe and
      effective for the treatment of central lung cancer, with mostly tolerable early
      complications. In this study, we report the development of severe obstructive
      atelectasis as a late complication in two patients with central lung cancer who
      received SBRT. This obstructive atelectasis interrupted the evaluation of
      efficacy of the subsequent gefitinib treatment for non-small-cell lung cancer
      (NSCLC). The two patients received a total dose of 40 Gy encompassing the
      planning target volume in 10 fractions (5 fractions/week) at 4 Gy per fraction at
      the central lesions. Obstructive atelectasis occurred when the patients received
      subsequent gefitinib treatment. Follow-up reviews or positron emission tomography
      computed tomography examination of the two patients confirmed that obstructive
      atelectasis was actually caused by radiotherapy rather than disease progression.
      Misjudgement of the cause of ostructive atelectasis in one of the cases resulted
      in premature termination of gefitinib. Therefore, it is crucial to accurately
      determine the cause of late complications in NSCLC patients receiving sequential
      SBRT and gefitinib.

PMID- 24940491
TI  - Overexpression of G protein-coupled receptor 87 correlates with poorer tumor
      differentiation and higher tumor proliferation in non-small-cell lung cancer.
AB  - G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the
      transmembrane G protein-coupled receptor family. Recently, GPR87 was suggested to
      contribute to the viability of human tumor cells and overexpression of GPR87 mRNA
      was detected in a number of malignant tumors, including lung cancer. We performed
      a retrospective study of GPR87 expression in association with clinical
      characteristics and biological markers in non-small-cell lung cancer (NSCLC). We
      investigated a total of 123 patients with NSCLC who underwent surgery between
      1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others).
      Immunohistochemistry was used to evaluate the intratumoral expression of GPR87
      and the Ki-67 proliferation index. The TUNEL method was also used to investigate
      tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87-positive.
      These tumors were more frequently encountered among squamous cell carcinomas
      rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and
      were significantly more frequently poorly and moderately differentiated rather
      than well differentiated (P=0.029). Moreover, the Ki-67 index was significantly
      higher in GPR87-positive compared to GPR87-negative tumors (57.0 vs. 40.0%,
      respectively; P=0.002). The overall survival was significantly worse for patients
      with GPR87-positive compared to those with GPR87-negative tumors (P=0.029). The
      Cox regression analyses also demonstrated that the GPR87 status was a significant
      prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present
      study demonstrated that in NSCLC, the overexpression of GPR87 is significantly
      associated with poorer differentiation and higher proliferation. During the
      progression of NSCLC, GPR87 overexpression may be associated with the acquisition
      of a more aggressive phenotype and, therefore, is a potentially useful target for
      prognostication and treatment.

PMID- 24940493
TI  - Endovascular management of two episodes of late intraperitoneal hemorrhage
      following laparoscopic gastrectomy for gastric cancer.
AB  - Endovascular treatment for hemorrhagic complications following surgery has
      recently gained wide acceptance due to its minimal invasiveness compared to
      surgery. A 56-year-old male patient underwent laparoscopic gastrectomy for
      gastric cancer. There were two episodes of late intraperitoneal hemorrhage and
      endovascular treatment was performed. Transcatheter coil embolization of the
      gastroduodenal artery stump was successful in controlling the bleeding initially;
      however, hemorrhage recurred 7 days later. Repeated angiography revealed an
      obvious hemorrhage from the right gastric artery stump and embolization of the
      hepatic artery proper was performed to achieve immediate hemostasis. The
      endovascular treatment process was analyzed and the literature on similar
      situations was reviewed. In the present case, endovascular procedures were
      performed successfully to control bleeding in two episodes of late
      intraperitoneal hemorrhage. Angiography is recommended as the first-line modality
      for late intraperitoneal hemorrhage following laparoscopic gastrectomy and
      transcatheter coil embolization of the hepatic artery proper is safe and
      effective in selected cases.

PMID- 24940492
TI  - Cyclin D1 expression in Bowen's disease and cutaneous squamous cell carcinoma.
AB  - Cyclin D1 is a member of the G1 cyclin family that regulates the transition
      through the G1 phase of the cell cycle and is involved in the neoplastic
      transformation of certain tumors. This study was designed to investigate the
      expression of cyclin D1 in Bowen's disease (BD) and cutaneous squamous cell
      carcinoma (SCC). Biopsies of 30 cases with BD and 24 cases with SCC confirmed by
      histopathology were obtained from the Department of Dermatology of Huashan
      Hospital, Shanghai, China. EnVision immunohistochemical technology with a
      semiquantitative immunohistochemical score was applied to detect the expression
      of cyclin D1. Of the 24 specimens with SCC, cyclin D1 was found to be positive in
      17 (70.8%), whereas of the 30 specimens with BD, cyclin D1 was found to be
      positive in 13 (43.3%). The expression of cyclin D1 was significantly higher in
      the SCC compared to that in the BD group. We did not observe a significant
      association of cyclin D1 expression with different pathological grades of SCC. In
      conclusion, cyclin D1 plays a significant role as a diagnostic marker in skin
      tumors and its overexpression was not found to be correlated with the degree of
      differentiation of SCC.

PMID- 24940494
TI  - Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation
      induced fibrosis in patients with nasopharyngeal carcinoma.
AB  - Radiation-induced fibrosis is one of the late complications of radiotherapy (RT)
      for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the
      association between X-ray repair cross-complementing protein 1 and 3 (XRCC1 and
      XRCC3, respectively) gene haplotypes and radiation-induced fibrosis in NPC
      patients. Genomic DNA was extracted from blood samples of 120 NPC patients
      previously treated with RT. In total, 12 tag single-nucleotide polymorphisms
      (SNPs) were selected from the XRCC1 and XRCC3 genes and were genotyped using
      restriction fragment length polymorphism analysis or unlabeled probe melting
      analysis. Single-marker and haplotype analyses were performed using multivariate
      logistic regression analysis. The functional variant rs861539 of XRCC3 may be
      associated with radiation-induced fibrosis [asymptotic P-value (Pasym)<0.05]. No
      significant association was observed between radiation-induced fibrosis and any
      of the tag SNPs of XRCC1 and XRCC3 in either single-marker or haplotype analysis
      after 10,000 permutations [empirical P-value (Pemp)>0.05]. Our preliminary
      results indicated that the rs861539 variant of XRCC3 may be associated with an
      increased risk of radiation-induced fibrosis; however, a large-scale study is
      required to confirm this result.

PMID- 24940495
TI  - Comparison of serum human epididymis protein 4 and carbohydrate antigen 125 as
      markers in ovarian cancer: A meta-analysis.
AB  - Ovarian cancer (OC) is the third most common type of gynecological cancer.
      Measurements of human epididymis protein 4 (HE4) levels have been suggested for
      improving the specificity of the laboratory identification of OC. For this meta
      analysis, the Medline, Embase and Cochrane databases were searched to identify
      relevant studies. All the included studies for diagnostic performance were
      combined with sensitivity, specificity, positive likelihood ratio, negative
      likelihood ratio, diagnostic odds ratios (DORs) with 95% confidence intervals
      (CIs), summary receiver operating characteristic (SROC) curves and areas under
      the SROC curves (AUC). A total of 25 studies including 4,729 patients were
      identified as eligible for inclusion in the final analysis. The pooled
      sensitivities and respective 95% CIs for HE4 and carbohydrate antigen 125 (CA125)
      were 0.74 (0.72-0.76) and 0.74 (0.72-0.76), respectively. The pooled
      specificities and respective 95% CIs for HE4 and CA125 were 0.90 (0.89-0.91) and
      0.83 (0.81-0.84), respectively. The summary DORs and 95% CIs for HE4 and CA125
      were 43.35 (29.13-64.51) and 17.06 (10.97-26.51), respectively and the AUCs for
      HE4 and CA125 were 0.8915 and 0.8538, respectively. In total, 9 studies
      investigated the diagnostic accuracy of HE4 combined with CA125 for the diagnosis
      of OC. The pooled sensitivity and 95% CIs of HE4, CA125 and HE4+CA125 in this
      subgroup were 0.71 (0.67-0.75), 0.74 (0.69-0.78) and 0.90 (0.87-0.92),
      respectively; the pooled specificity and 95% CIs of HE4, CA125 and HE4+CA125 were
      0.92 (0.90-0.94), 0.73 (0.69-0.76) and 0.85 (0.82-0.87), respectively. The
      diagnostic accuracy of HE4 in distinguishing OC from other benign gynecological
      diseases was found to be to be superior to that of CA125 and the combination of
      HE4 and CA125 may enhance the diagnostic sensitivity.

PMID- 24940496
TI  - Marked tumor response to crizotinib after 4 years of maintenance pemetrexed in a
      patient with anaplastic lymphoma kinase-positive non-small-cell lung cancer.
AB  - Maintenance therapy with pemetrexed is well tolerated and achieves prolonged
      progression-free and overall survival in patients with advanced lung
      adenocarcinoma. The echinoderm microtubule-associated protein-like 4 (EML4)
      anaplastic lymphoma kinase (ALK) is a recently identified fusion oncogene that
      exists in ~5% of non-small-cell lung cancers (NSCLCs). It was demonstrated that
      ALK-positive NSCLCs exhibit a high response rate to the ALK inhibitor crizotinib.
      This is the case report of a patient with NSCLC harboring EML4-ALK rearrangement,
      who experienced slowly progressive disease within 4 years of maintenance
      treatment with pemetrexed and later exhibited a marked response to crizotinib.
      The sustained clinical benefits suggest further investigations on anticancer
      agent administration.

PMID- 24940497
TI  - Factors affecting long-term survival in elderly patients undergoing radiotherapy
      for esophageal carcinoma.
AB  - This study was conducted with the aim to analyze the factors affecting the 1-, 3-
      and 5-year survival rate of elderly patients with esophageal carcinoma. Between
      2004 and 2008, a total of 371 patients aged >=70 years treated with radiotherapy
      alone were enrolled in this study. The clinical characteristics and radiotherapy
      dose were evaluated by survival rate and the 1-, 3- and 5-year overall survival
      (OS) rates were found to be 42, 13.2 and 9.16%, respectively. The univariate
      analysis revealed significant differences in T, N, M and clinical stage and
      radiotherapy dose (all P-values <0.05) and no significant differences in gender
      (all P-values >0.05). There was a difference in tumor location when only
      comparing the 3- and 5-year OS rates (P=0.031 and P=0.025, respectively). The
      multivariate analysis identified clinical stage as an independent factor for the
      1-year OS rate (P=0.003), whereas radiotherapy dose and clinical stage were found
      to be independent factors for the 3- and 5-year OS rates (all P-values 0.05). In
      the analysis of radiotherapy dose, we observed no significant difference in the 1
      year OS rate between the radiation dose (DT) >60 Gy and the 50 Gy<=DT<60 Gy
      groups (P=0.363); however, there were statistically significant differences in
      the 3-year OS rate between the 50 Gy<=DT<60 Gy and the other groups (P=0.039 and
      P=0.032); there were no significant differences in the 5-year OS rate among the
      dose groups (all P-values >0.05). In conclusion, according to the findings of
      this retrospective study, radiotherapy alone for elderly patients with esophageal
      cancer does not appear to be acceptable and there is a need for a more effective
      treatment. T, N, M and clinical stage and radiotherapy dose were identified as
      factors significantly affecting the 1-, 3- and 5-year OS in elderly patients with
      esophageal carcinoma, although a higher radiotherapy dose with normal
      fractionation did not appear to improve the OS rate.

PMID- 24940498
TI  - Prognostic role of substaging in T1G3 transitional cell carcinoma of the urinary
      bladder.
AB  - This study was conducted to test a new substaging system in a population of
      patients with stage T1 bladder cancer (BC) at diagnosis and assess its prognostic
      role in terms of disease progression and disease-specific survival (DSS).
      Patients with primary stage T1G3 urothelial carcinoma of the bladder were
      stratified according to the following models: i) T1a [the tumour does not
      infiltrate the muscularis mucosae-vascular plexus, (MM-VP)]; T1b (the tumour
      partially infiltrates the MM-VP); and T1c (the tumour infiltrates and invades the
      MM-VP). ii) T1m (diameter of tumour infiltrating the lamina propria <=0.5 mm
      under a high-resolution microscope; and T1e (diameter of tumour infiltrating the
      lamina propria >0.5 mm). Age, gender, tumour size and multifocality were not
      found to be of statistical significance. Using the T1a/T1b/T1c system, patients
      with stage T1a disease exhibited a 5- and 10-year progression rate of 13.3 and
      20%, respectively, without reaching statistical significance. Moreover, patients
      with stage T1a disease exhibited a 5- and 10-year DSS of 93.3 and 73.3%,
      respectively, which was higher compared to T1b and T1c but not statistically
      significant. Using the T1m/T1e system, patients with stage T1m disease exhibited
      a disease progression rate of 8.3 and 16.7% at 5 and 10 years, respectively,
      which was not statistically significant. Moreover, patients in group T1m
      presented with DSS rates of 91.7 and 83.3% at 5 and 10 years, respectively, which
      were higher compared to those in the T1e group (71.4 and 60.7%), although not
      reaching statistical significance. In conclusion, in our study, neither of the
      two substaging systems of stage T1 BC reached the prognostic conventional
      significance level for tumour progression or DSS.

PMID- 24940499
TI  - Free-B-Ring flavonoids as potential lead compounds for colon cancer therapy.
AB  - Although flavonoids have been identified as a versatile source of anticancer
      agents, to the best of our knowledge, no study has yet investigated their
      anticolon cancer activity in depth. Therefore, the aim of this study was to
      investigate the association between the structural characteristics of flavonoids
      and their anticolon cancer activity in the Caco-2 human colon cancer cell line.
      Our findings demonstrated that the hydroxylation of C5 and C7 in ring A
      significantly enhanced the anticolon cancer activity of flavonoids over that of 5
      fluorouracil, the classic reference cytotoxic agent. By contrast, the
      glycosylation or the presence of hydroxyl groups in ring B significantly
      decreased flavonoid anticancer activity. Collectively, these findings suggest a
      novel, rational design of flavonoid-related compounds that may improve the
      treatment of colorectal cancer.

PMID- 24940500
TI  - Phase I trial of M2ES, a novel polyethylene glycosylated recombinant human
      endostatin, plus gemcitabine in advanced pancreatic cancer.
AB  - Pancreatic cancer is one of the most lethal and resistant to treatment of solid
      tumors. Combination therapies with various types of drugs against pancreatic
      cancer have been extensively investigated. Endostatin is a potent endogenous
      inhibitor of angiogenesis, which may be administered in combination with various
      chemotherapeutic agents in the treatment of several types of cancer. To the best
      of our knowledge, this phase I trial was the first clinical study to determine
      the tolerance, safety and efficacy of M2ES, a novel polyethylene glycosylated
      recombinant human endostatin, administered concurrently with full-dose
      gemcitabine in patients with inoperable, locally advanced or metastatic
      pancreatic adenocarcinoma. A total of 16 patients were treated with gemcitabine
      (1,000 mg/m2 on days 1, 8 and 15) and M2ES (5-45 mg/m2 on days 1, 8, 15 and 21)
      of each 28-day cycle. In 15 evaluable patients, the stable disease rate (SDR) was
      40% (95% CI: 11.9-68.1%). In particular, a 75% SDR was observed in 3 out of 4
      patients with a M2ES dose level of 7.5 mg/m2. The most noticeable M2ES-related
      adverse events observed during the trial were grade 2 liver function
      abnormalities (6.3%) and grade 1 skin rash (6.3%). No dose-limiting toxicity was
      observed in any patients from all the dose levels. Therefore, there was no
      increased toxicity associated with the addition of M2ES to gemcitabine and this
      combination was well tolerated.

PMID- 24940501
TI  - A retrospective study on combination therapy with ifosfamide, adriamycin and
      cisplatin for progressive or recurrent uterine sarcoma.
AB  - There is currently insufficient evidence to recommend a specific chemotherapeutic
      regimen as standard treatment for uterine sarcomas. In this study, we
      investigated the toxicity and effectiveness of ifosfamide, adriamycin and
      cisplatin (IAP therapy) in patients with progressive and recurrent uterine
      sarcoma. A total of 11 patients with progressive or recurrent uterine sarcoma
      containing leiomyosarcoma (LMS), undifferentiated endometrial sarcoma (UES) or
      adenosarcoma, who were diagnosed at our institution, were retrospectively
      investigated. We recorded the adverse events, response rate and progression-free
      survival in these cases. The histological types included LMS (54.5%),
      adenosarcoma (27.3%) and UES (18.2%). Grade >=3 leukopenia or neutropenia were
      observed in all the cases, febrile neutropenia developed in 45.5% of the patients
      and grade 4 thrombocytopenia developed in 3 cases (27.3%). With IAP therapy, the
      response rate was 36.4% and the disease control rate was 90.9%. Therefore, IAP
      therapy may be a viable option as chemotherapy for uterine sarcoma.

PMID- 24940502
TI  - Alopecia areata as a paraneoplastic syndrome of Hodgkin's lymphoma: A case
      report.
AB  - Alopecia areata (AA) has been classically associated with several autoimmune
      disorders. However, AA as a paraneoplastic syndrome of Hodgkin's lymphoma (HL)
      remains a rare entity and our understanding of this phenomenon is limited to a
      few case reports. This is the case report of a 46-year-old male patient who was
      diagnosed with AA several months prior to the onset of B symptoms and the
      diagnosis of stage IVB classical HL. The patient was subsequently treated with 6
      cycles of adriamycin, bleomycin, vinblastine and dacarbazine and experienced a
      complete response and resolution of his AA. In our case, the onset of AA preceded
      the onset of systemic manifestations and diagnosis of HL, whereas in other cases
      AA was shown to occur concurrently with the clinical manifestations of HL. In all
      the cases, however, treatment of the HL subsequently led to resolution of the AA.
      The present case report highlights the significance of AA as a herald of
      underlying malignancy, although AA in classical HL remains poorly characterized
      in the literature.

PMID- 24940503
TI  - Evaluation of endoscopic cytological diagnosis of unresectable pancreatic cancer
      prior to and after the introduction of endoscopic ultrasound-guided fine-needle
      aspiration.
AB  - With the advances in the multidisciplinary treatment of pancreatic cancer (PC)
      over the last few years, it is crucial to obtain a histopathological diagnosis
      prior to treatment. Histopathological diagnosis for unresectable PC is currently
      performed with endoscopic retrograde cholangiopancreatography (ERCP) in
      combination with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).
      We retrospectively assessed the results of these two methods and investigated
      diagnostic performance according to the location of the lesion and the
      complications. This study was conducted on a series of 263 consecutive cases of
      unresectable PC diagnosed with endoscopic cytology. Up to 2006, ERCP-guided
      cytology (group A) was performed as the first choice for the diagnosis of PC. EUS
      FNA was introduced in 2007 and became the first choice thereafter (group B),
      except in cases with obstructive jaundice, in which ERCP-guided cytology during
      endoscopic biliary stenting (EBS) remains the first choice. There were
      statistically significant differences in the overall cancer-positive rate between
      groups A and B (60.4 vs. 75.3%, P=0.01). The cancer-positive rate in the
      pancreatic body and tail was significantly higher in group B (59.5 vs. 83.3%,
      P=0.005), whereas there were no significant differences regarding cancer of the
      pancreatic head. The complication rate was 4.95% in group A and 3.09% in group B
      (P=0.448). The endoscopic cytology cancer-positive rate in unresectable PC cases
      was increased as a result of the introduction of EUS-FNA. In conclusion, we
      recommend performing EUS-FNA in combination with ERCP-guided cytology in cases
      with a lesion in the pancreatic head that requires EBS.

PMID- 24940504
TI  - Efficacy of tyrosine kinase inhibitors in non-small-cell lung cancer patients
      undergoing dose reduction and those with a low body surface area.
AB  - The objective of this study was to evaluate the efficacy of epidermal growth
      factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients undergoing
      dose reduction and in those with a low body surface area (BSA). The association
      between dose reduction, low BSA and efficacy, including response rate (RR),
      disease control rate (DCR), progression-free survival (PFS) and overall survival
      (OS), were evaluated in patients prescribed TKIs between September, 2002 and May,
      2013. A total of 282 patients received EGFR-TKIs during the study period, 53
      (18.8%) of whom underwent a dose reduction (21.4 and 31.6% of the patients with a
      BSA of <1.5 and <1.25 m2, respectively). Eleven (20.8%) of these 53 patients had
      a dose reduction due to adverse events (AEs) >grade 3. In either gefitinib or
      erlotinib treatment, the RR, DCR, PFS and OS in EGFR-mutated patients with a BSA
      of <1.5 m2 were not different from those in patients with a BSA of >1.5 m2. In
      addition, there were no differences in these parameters between patients with and
      those without a dose reduction of TKIs. The dose of TKIs in patients with AEs and
      in those with low BSA should be determined with caution. To confirm the equal
      efficacy of TKIs in patients undergoing a dose reduction, prospective
      observational studies with less patient heterogeneity are required.

PMID- 24940505
TI  - Controlling distant metastasis and surgical treatment are crucial for improving
      clinical outcome in uncommon head and neck malignancies, such as non-squamous
      cell carcinoma.
AB  - The objective of this study was to elucidate the clinical characteristics of
      uncommon head and neck malignancies, such as non-squamous cell carcinoma (SCC),
      in order to improve patient outcomes. A total of 463 head and neck malignancies
      were retrospectively analyzed, with 43 cases (9.3%) diagnosed as non-SCC. The
      overall survival rate of patients with adenoid cystic carcinoma was significantly
      worse compared to that of patients with SCC. The 5-year survival rates were <50%
      for patients with malignant melanoma, adenocarcinoma, small-cell carcinoma and
      sarcomas. Distant metastasis to the lung was frequently observed in cases with a
      poor outcome. Non-SCC malignancies treated without surgery were associated with a
      worse outcome. Some non-SCC patients had a poor prognosis and distant metastasis
      was associated with an unsatisfactory outcome. Timely treatment and control of
      distant metastasis are essential and surgical treatment should be prioritized in
      non-SCC cases to improve patient outcomes.

PMID- 24940506
TI  - Differences in carcinoembryonic antigen levels between colon and rectal cancer.
AB  - The aim of the present study was to investigate the levels of the serum tumor
      biomarker carcinoembryonic antigen (CEA) in patients with carcinoma of the colon
      and rectum in different clinical stages. Colorectal cancer (CRC) is one of the
      most commonly diagnosed types of cancer worldwide and previous studies have
      reported rapidly updated therapeutic regimes. While the majority of studies focus
      on CRC as a single entity, certain studies distinguish colon cancer (CC) from
      rectal cancer (RC), as there is a hypothesis stating that CC and RC are two
      naturally different entities. CEA is reported to be an important tumor-associated
      antigen overexpressed in CRC, which is routinely detected as a significant
      indicator of CRC. Our study aimed to identify potential differences in the
      expression of CEA between CC and RC, which may, to some degree, reflect the
      natural differences between the two. We investigated 240 CRC cases between July,
      2010 and December, 2012 from The First and Second Affiliated Hospitals of Dalian
      Medical University, including 117 CC and 123 RC patients with tumors classified
      by Duke's staging as A-D. The serum CEA level was measured preoperatively by
      radioimmunoassays as a routinely used auxiliary indicator. The expression of CEA
      differed between CC and RC, with the former exhibiting variation among the four
      stages, whereas no variation was observed in RC. In addition, there were
      differences between CC and RC regarding the CEA level in stage C and D.
      Furthermore, the CEA level in stage C of CC was significantly lower compared to
      that in any other stage. In conclusion, the intrinsic distribution of the CEA
      level between CC and RC suggests that CC and RC may be two naturally different
      entities; the significantly low CEA level in stage C of CC indicates that stage C
      may be crucial in the evolution of CC.

PMID- 24940507
TI  - Association between mammographic features and clinicopathological characteristics
      in invasive ductal carcinoma of breast cancer.
AB  - The aim of the present study was to evaluate the association between mammographic
      features and clinicopathological characteristics in invasive ductal carcinoma. A
      total of 231 patients were retrospectively reviewed from January, 2011 to
      December, 2012. Statistical analysis was performed using Fisher's exact test,
      chi2 test, Spearman's correlation and logistic regression, as appropriate. Of the
      231 patients who underwent mammography, malignant calcifications were
      significantly more frequent in carcinomas that were human epidermal growth factor
      receptor 2 (HER2)-positive (P=0.001) or had a >2 cm size tumor (P=0.006). The
      pleomorphic-type was correlated with a p53-positive status (P=0.039) or lymph
      node metastasis (P=0.048), whereas the indistinct amorphous-type was associated
      with a HER2-positive status (P=0.026). An evident mass was frequently observed in
      higher Ki-67 expression-level tumors (P=0.002). In conclusion, the aforementioned
      correlations are noteworthy as they potentially reflect tumor attributes and may
      serve as a guide for treatment.

PMID- 24940508
TI  - GALNT14 genotype, alpha-fetoprotein and therapeutic side effects predict post
      chemotherapy survival in patients with advanced hepatocellular carcinoma.
AB  - In addition to targeted agents, chemotherapy is currently considered to be a
      treatment option for patients with advanced hepatocellular carcinoma (HCC);
      however, it is associated with severe side effects that may limit its clinical
      use. UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetyl
      galactosaminyltransferase 14 (GALNT14) genotype was previously identified as a
      prognostic marker for HCC patients receiving 5-fluorouracil, mitoxantrone and
      cisplatin (FMP) combination chemotherapy. The present study aimed to assess
      clinical parameters and on-treatment side effects as effective predictors for
      favorable prognosis. A total of 118 patients with HCC receiving split-dose FMP
      were retrospectively enrolled. The clinical parameters, side effects and GALNT14
      genotype were analyzed. The independent predictors for time-to-progression (TTP)
      and overall survival (OS) were assessed using Cox proportional hazards models.
      Following categorization, the Kaplan-Meier method was used to compare survival
      outcomes. Pretreatment alpha-fetoprotein (AFP) <=2,800 ng/ml (median level),
      GALNT14 'TT' genotype, on-treatment leukopenia and absence of vomiting were
      identified as independent predictors of a favorable TTP (P=0.001, 0.035, 0.008
      and 0.009, respectively) and OS (P=0.028, 0.006, 0.027 and 0.013, respectively).
      A total of 59 patients with AFP <=2,800 ng/ml exhibited longer median TTP and OS
      (3.11 vs. 1.75 months, P<0.001; and 8.14 vs. 3.79 months, P<0.001, respectively).
      A total of 30 patients with the GALNT14 'TT' genotype exhibited longer median TTP
      and OS (3.11 vs. 2.11 months, P=0.014; and 5.75 vs. 3.93 months, P=0.001,
      respectively). Finally, 9 patients (9/118; 7.6%) with all four favorable factors
      exhibited the longest median TTP and OS (10.64 vs. 2.07 months, P=0.002; and
      25.50 vs. 4.50 months, P<0.001, respectively). In conclusion, the AFP level and
      the GALNT genotype may be considered as pre-therapeutic predictors of a favorable
      response. When combined with on-treatment leukopenia and absence of vomiting, a
      subgroup of patients with excellent outcome may be identified.

PMID- 24940509
TI  - Prevalence and correlates of unhealthy weight control behaviors: findings from
      the national longitudinal study of adolescent health.
AB  - BACKGROUND: A recent study examined the prevalence, clinical correlates, age
      trends, and stability of unhealthy weight control behaviors (UWCB; purging and
      diet pill use) in a nationally representative sample of Norwegian boys and girls.
      The purpose of this study was to provide similar, comparative analyses for a
      nationally representative sample of American youth. METHODS: Data were extracted
      from the restricted use data files of survey Waves I, II, and III of the National
      Longitudinal Study of Adolescent Health (Add Health), selecting all participants
      who at Wave I had provided information on age, sex, and UWCB. Using UWCB
      information, three groups were created (purging, diet pill use, and no recent
      UWCB "controls") and compared on indicators of adverse health or mental health.
      RESULTS: Girls consistently were more likely than boys to report UWCB. UWCB were
      significantly associated with higher body mass index, self-perception of being
      overweight, low self-esteem, depression, and delinquency. Prevalence estimates
      for purging remained relatively constant across the three survey waves; in
      contrast, diet pill use was especially common at Wave III. CONCLUSIONS: Age
      trends, gender differences, and clinical correlates of change in the likelihood
      of UWCB between Waves I-III were all identified in analyses comparing purging and
      diet pill use in American adolescents. Females and older adolescents were
      specifically more likely to engage in pill use than purging, and individuals with
      increased weight dissatisfaction, a history of delinquent behaviors, more
      depression symptoms, or lower self-esteem were more likely to engage in an
      unhealthy weight control behavior over time. While the Norwegian study found that
      prevalence of purging was lower among young adult participants, our results
      suggested that there were no significant differences in prevalence between age
      groups.

PMID- 24940510
TI  - Characterization of beta -Glucosidase Produced by Aspergillus niger under Solid
      State Fermentation and Partially Purified Using MANAE-Agarose.
AB  - beta -Glucosidase (BGL) is a hydrolytic enzyme with specificity for a wide
      variety of glycoside substrates, being an enzyme with a large range of
      biotechnological applications. However, enzyme properties can be different
      depending both on the microorganism and the cultivation procedure employed.
      Therefore, in order to explore potential biocatalytical applications of novel
      enzymes, their characterization is essential. In this work, a BGL synthesized by
      a selected strain of Aspergillus niger cultivated under solid-state fermentation
      (SSF) was partially purified and fully characterized in terms of optimum pH,
      temperature, and thermostability. The single-step purification using MANAE
      agarose in a chromatographic column yielded an enzyme solution with specific
      activity (17.1 IU/mg protein) adequate for the characterization procedures.
      Electrophoresis SDS-PAGE and size-exclusion chromatography analysis resulted in
      an estimated molecular mass of 60 kDa. Higher enzyme activities were found in the
      range between 40 and 65 degrees C and between pH 4 and 5.5, indicating an
      interesting characteristic for application in the hydrolysis of lignocellulosic
      biomass for biofuels production. Thermostability studies of purified BGL resulted
      in half-lives at 37 degrees C of 56.3 h and at 50 degrees C of 5.4 h. These
      results provide support for further studies of this enzyme towards revealing its
      potential biotechnological applications. 

PMID- 24940511
TI  - Capsule Endoscopy in a Patient with an Implanted CCM System and an Implantable
      Defibrillator.
AB  - Wireless video capsule endoscopy (CE) is a modern diagnostic tool. Because of its
      use of digital radiofrequency, it is still relatively contraindicated in patients
      with implanted cardiac devices. We report the case of a patient with an Optimizer
      III system delivering cardiac contractility modulating signals (CCM) for heart
      failure therapy and an implantable cardioverter defibrillator (ICD) who underwent
      CE. No interferences between the devices were found. 

PMID- 24940512
TI  - Possible usefulness of gadolinium-enhanced brain MRI for evaluating risk of
      perioperative hemorrhage: a case of infective endocarditis.
AB  - A 59-year-old woman visited a local hospital for fever and was diagnosed as
      having infective endocarditis (IE) on the basis of blood cultures and
      transthoracic echocardiography. Based on clinical episodes of subarachnoid
      hemorrhage after admission, it was judged that she was not a good candidate for
      urgent open heart surgery, and it was decided to treat her with conservative
      medical therapy for the acute phase. We explored the optimum timing for surgery
      by employing gadolinium (Gd) contrast medium-enhanced magnetic resonance imaging
      (MRI) T2* weighted image (black dots) due to her high risk of perioperative
      cerebral hemorrhage. After the disappearance of the contrast media enhancement
      effect around the black dots, open heart surgery was performed successfully on
      the 103rd hospitalization day. The patient was discharged 22 days after the
      surgery with no clinical complications. This case suggests that disappearance of
      the contrast media enhancement effect around the black dots may be a useful
      marker for optimal timing of surgery to minimize the risk of perioperative
      cerebral hemorrhage in patients with IE. Learning Objective. The MRI T2* weighted
      images including those with Gd contrast medium enhancement effect may be useful
      for evaluating the risk of perioperative intracranial hemorrhage in IE. 

PMID- 24940513
TI  - Smoking and other drug characteristics of aboriginal and non-aboriginal prisoners
      in australia.
AB  - Introduction and Aim. Although tobacco and alcohol use have declined
      substantially in the Australian community, substance use among prisoners remains
      high. The aim was to compare the smoking, drug, and alcohol characteristics,
      sociodemographic profile, and general health of Aboriginal and non-Aboriginal
      male prisoners in a smoking cessation intervention. Design and Methods. This
      study was a descriptive cross-sectional analysis of data from 425 male prisoners
      who joined a quit smoking trial conducted at 18 correctional centres in NSW and
      Queensland using data collected by standardised self-report instruments. Results.
      Average age was 33 years with 15% from Aboriginal descent. Compared to non
      Aboriginal prisoners, Aboriginal prisoners were significantly more likely to have
      left school with no qualifications, to have been institutionalised as a child, to
      be previously incarcerated, and commenced smoking at a younger age. The tobacco
      use profile of both groups was similar; most of them had a medium to high level
      of nicotine dependence, smoked roll your own tobacco, and were "serious" about
      quitting. Discussion and Conclusion. Despite differences in terms of
      sociodemographic characteristics and offending history, the smoking
      characteristics of Aboriginal and non- Aboriginal prisoners were similar.
      Incarceration offers an opportunity to encourage smoking cessation and reduction
      of drug use. 

PMID- 24940514
TI  - Interleukin-17A Exacerbates Ferric Chloride-Induced Arterial Thrombosis in Rat
      Carotid Artery.
AB  - Interleukin-17A (IL-17A), the most widely studied member of the IL-17 cytokine
      family, is a cytokine which emerged to be critical for host defense as well as in
      the pathogenesis of autoimmune disorders. Moreover, IL-17A is involved in the
      pathogenesis of cardiovascular diseases, such as atherosclerosis and acute
      coronary syndrome and in the cardiovascular risk associated with systemic
      immunological disorders. Consistent with this, we have recently shown that IL-17A
      increases human and murine platelet response to ADP. In this study we expanded
      our previous observation and we describe for the first time an in vivo
      prothrombotic effect of the cytokine. Our results show that IL-17A is synergic
      with a low FeCl3 concentration in inducing carotid thrombus in rats and suggest
      that the effect is likely related to a downregulation of CD39 vascular expression
      and hydrolyzing activity. Our findings indicate that IL-17A might be an important
      molecule at the interface between hemostasis and inflammation. "This paper is
      dedicated to the memory of Professor Alfredo Colonna" 

PMID- 24940516
TI  - A new era of collaboration for primary care and psychiatry.

PMID- 24940515
TI  - Out of sight, out of mind: the case of a 62-year-old man with visual complaints
      and cognitive decline.

PMID- 24940517
TI  - How to live with a terminal illness.

PMID- 24940518
TI  - Behavioral Management of Tourette's Disorder in a 5-Year-Old Child.

PMID- 24940519
TI  - A case of reversible erectile dysfunction with topiramate for alcohol dependence.

PMID- 24940520
TI  - Capgras' syndrome in an elderly patient with dementia.

PMID- 24940521
TI  - A case of psychogenic non-epileptic seizures, unresponsive type, in pregnancy.

PMID- 24940522
TI  - A case of mouthwash as a source of ethanol poisoning: is there a need to limit
      alcohol content of mouthwash?

PMID- 24940524
TI  - Efficacy and safety of low-dose doxepin in depressed patients suffering from
      insomnia: a retrospective, naturalistic case series analysis.
AB  - OBJECTIVE: Low-dose doxepin has produced favorable results in healthy adults and
      elderly persons with chronic or transient insomnia, while exhibiting an amenable
      adverse event profile. The aim of this article is to investigate the efficacy and
      safety of low-dose doxepin for insomnia in depressed patients. METHOD: In this
      retrospective case series analysis, the files of 17 inpatients diagnosed with
      major depressive disorder (MDD) and comorbid insomnia between January 1, 2011,
      and October 1, 2012 who had received a course of off-label doxepin (< 25 mg/d)
      were analyzed with regard to dose, efficacy, and safety for up to 4 weeks of
      treatment. Hamilton Depression Rating Scale (HDRS) sleep item scores were used to
      estimate efficacy. RESULTS: Our results showed no improvement in sleep onset and
      sleep maintenance insomnia in patients with MDD during the 4 weeks of treatment.
      We found a significant improvement in insomnia between baseline and week 3 when
      considering all 3 HDRS sleep items (P = .058). CONCLUSION: Contrasting previous
      results in healthy subjects, low-dose doxepin does not seem to improve sleep
      onset or maintenance in patients with MDD. Further research, preferably placebo
      controlled, double-blind sleep laboratory trials, is necessary to determine
      whether low-dose doxepin may be beneficial in this important patient subgroup.

PMID- 24940523
TI  - Prevalence of substance misuse in new patients in an outpatient psychiatry clinic
      using a prescription monitoring program.
AB  - OBJECTIVE: To investigate the value of a prescription monitoring program in
      identifying prescription drug misuse among patients presenting to a resident
      physician outpatient psychiatry clinic at an academic medical center. METHOD:
      Participants were 314 new patients aged 18 years or older presenting to the
      clinic from October 2011 to June 2012. Resident physicians completed a data
      collection form for each participant using information from the patient interview
      and from the prescription monitoring program report. Prescription drug misuse was
      defined as having any 1 of the following 5 criteria in the prescription
      monitoring program report: (1) filled prescriptions for 2 or more controlled
      substances, (2) obtained prescriptions from 2 or more providers, (3) obtained
      early refills, (4) used 3 or more pharmacies, and (5) the prescription monitoring
      program report conflicted with the patient's report. RESULTS: At least 1
      indicator of prescription drug misuse was found in 41.7% of patients. Over 69% of
      the patients that the residents believed were misusing prescription drugs
      actually met 1 of the criteria for prescription drug misuse. The prescription
      monitoring program report changed the management only 2.2% of the time. Patients
      with prior benzodiazepine use (chi(2) 1 = 17.68, P < .001), prior opioid use
      (chi(2) 1 = 19.98, P < .001), a personality disorder (chi(2) 1 = 7.22, P < .001),
      and chronic pain (chi(2) 1 = 14.31, P < .001) had a higher percentage of
      prescription drug misuse compared to patients without these factors. CONCLUSION:
      Using the prescription monitoring program to screen patients with prior
      benzodiazepine and opioid use, with a personality disorder, and/or with chronic
      pain may be useful in confirming the suspicion of prescription drug misuse
      identified at the initial evaluation.

PMID- 24940525
TI  - Clinical relevance of vilazodone treatment in patients with major depressive
      disorder: categorical improvement in symptoms.
AB  - OBJECTIVE: To assess clinically relevant symptom improvement in patients with
      major depressive disorder (MDD) receiving vilazodone by using the Montgomery
      Asberg Depression Rating Scale (MADRS), a clinician-rated scale used to measure
      MDD symptom severity and improvement. METHOD: Pooled data from 2 positive, phase
      3, 8-week, double-blind, randomized, placebo-controlled trials in patients with
      MDD were analyzed. Patients received vilazodone 40 mg/d or placebo; post hoc
      analyses were conducted on study completers. Depression symptom improvement was
      evaluated by analyzing the proportions of patients who shifted from the baseline
      MADRS single-item symptom severity category of >= 2 (mild to severe symptoms) to
      an end-of-study category < 2 (minimal to no symptoms) or from >= 4 (moderate to
      severe symptoms) to <= 2 (mild to no symptoms). The proportion of patients who
      shifted from anxious depression to no anxious depression was also analyzed.
      RESULTS: The percentage of patients who completed these studies with severity
      category shift from baseline >= 2 to end of study < 2 was significantly higher
      for vilazodone versus placebo on all MADRS items (odds ratio [OR] range, 1.4-1.7,
      P < .05) except reduced appetite (OR = 1.3, P = .232). A significantly greater
      proportion of vilazodone-treated versus placebo-treated patients shifted from
      baseline >= 4 to end of study <= 2 on MADRS items of apparent sadness, reported
      sadness, inner tension, reduced sleep, and lassitude (OR range, 1.5-2.0, P <
      .05). Additionally, a significantly greater proportion of vilazodone-treated
      versus placebo-treated patients shifted from anxious depression at baseline to no
      anxious depression at end of study (OR = 1.5, P = .031). CONCLUSIONS: These
      results suggest that vilazodone treatment is associated with clinically relevant
      changes in depression symptoms in patients with MDD. TRIAL REGISTRATION:
      ClinicalTrials.gov identifiers: NCT00285376 and NCT00683592.

PMID- 24940526
TI  - Effect of probiotic supplementation on schizophrenia symptoms and association
      with gastrointestinal functioning: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: A range of immune system abnormalities have been associated with
      schizophrenia. Probiotic compounds modulate the immune response and offer a
      potential treatment strategy for schizophrenia. Probiotic compounds have also
      been observed to improve gastrointestinal dysfunction, which is a common problem
      in individuals with schizophrenia. We performed a randomized, double-blind,
      placebo-controlled trial to examine whether probiotic supplementation can reduce
      symptom severity in patients with schizophrenia receiving antipsychotic treatment
      and also whether probiotics are associated with bowel functioning. METHODS:
      Outpatients with schizophrenia (N = 65) meeting DSM-IV criteria and with at least
      moderately severe psychotic symptoms were enrolled in the study from December
      2010-August 2012. Following a 2-week placebo run-in period, patients were
      randomly assigned to 14 weeks of double-blind adjunctive probiotic (combined
      Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis
      strain Bb12) or placebo therapy. Psychiatric symptoms were assessed biweekly with
      the Positive and Negative Syndrome Scale (PANSS), and patients were queried
      weekly about their gastrointestinal functioning. RESULTS: Repeated-measures
      analysis of variance showed no significant differences in the PANSS total score
      between probiotic and placebo supplementation (F = 1.28, P = .25). However,
      patients in the probiotic group were less likely to develop severe bowel
      difficulty over the course of the trial (hazard ratio = 0.23; 95% CI, 0.09-0.61,
      P = .003). CONCLUSIONS: Probiotic supplementation may help prevent a common
      somatic symptom associated with schizophrenia. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01242371.

PMID- 24940528
TI  - A review of spin and bias use in the early intervention in psychosis literature.
AB  - OBJECTIVE: The early intervention in psychosis literature has recently
      appropriated clinical terms with etiologic implications such as staging and
      pluripotent from the oncology literature without adopting the methodological
      rigor of oncology research. Oncology research maintains this rigor, among other
      methods, by examining the literature for evidence of bias and spin, which
      obscures negative trials. This study was designed to detect possible use of
      reporting bias and spin in the early intervention in psychosis literature. DATA
      SOURCES: Articles were selected from PubMed searches for early intervention in
      psychosis, duration of untreated psychosis, first-episode psychosis, ultra-high
      risk, and at risk mental state between January 1, 2000, and May 31, 2013. STUDY
      SELECTION: 38 RCT and quasi-experimental articles reporting results from early
      intervention in psychosis paradigms were selected for inclusion. DATA EXTRACTION:
      Articles were examined for evidence of inappropriate reporting of primary and
      secondary end points in the abstract (reporting bias) and presentation as
      positive despite negative primary end points (spin). RESULTS: While only 13% of
      early intervention articles reported positive primary end points, abstracts
      implied that 76% of articles were positive. There was evidence of bias in 58% of
      articles and spin in 66% of articles. CONCLUSIONS: There was a high prevalence of
      spin and bias in the early intervention in psychosis literature compared to
      previous findings in the oncological literature. The most common techniques were
      changing the primary end point or focusing on secondary end points when the
      primary end point was negative and reporting analyses using only a subset of the
      data. There appears to be a need for greater scrutiny of the early intervention
      in psychosis literature by editors, peer reviewers, and critical readers of the
      literature.

PMID- 24940529
TI  - A Diversified Recruitment Approach Incorporating Social Media Leads to Research
      Participation Among Young Adult-Aged Female Cancer Survivors.
AB  - Purpose: Cancer survivors in their adolescent and young adult (AYA) years are an
      understudied population, possibly in part because of the high effort required to
      recruit them into research studies. The aim of this paper is to describe the
      specific recruitment strategies used in four studies recruiting AYA-aged female
      cancer survivors and to identify the highest yielding approaches. We also discuss
      challenges and recommendations. Methods: We recruited AYA-aged female cancer
      survivors for two studies conducted locally and two conducted nationally.
      Recruitment strategies included outreach and referral via: healthcare providers
      and clinics; social media and the internet; community and word of mouth; and a
      national fertility information hotline. We calculated the yield of each
      recruitment approach for the local and national studies by comparing the number
      that participated to the number of potential participants. Results: We recruited
      a total of 534 participants into four research studies. Seventy-one percent were
      diagnosed as young adults and 61% were within 3 years of their cancer diagnosis.
      The highest-yielding local recruitment strategy was healthcare provider and
      clinic referral. Nationally, social media and internet outreach yielded the
      highest rate of participation. Overall, internet-based recruitment resulted in
      the highest number and yield of participants. Conclusion: Our results suggest
      that outreach through social media and the internet are effective approaches to
      recruiting AYA-aged female cancer survivors. Forging collaborative relationships
      with survivor advocacy groups' members and healthcare providers also proved
      beneficial.

PMID- 24940527
TI  - A review of vilazodone, serotonin, and major depressive disorder.
AB  - OBJECTIVE: To review the mechanism of selective serotonin reuptake inhibitor
      (SSRI)-mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A)
      autoreceptors, which are proposed to be involved in delaying therapeutic
      efficacy. Vilazodone was specifically designed to function both as an SSRI and a
      partial agonist at 5-HT1A receptors. This combined mechanism is proposed to
      decrease time to efficacy, minimize sexual side effects, and provide concomitant
      anxiolytic properties. DATA SOURCES: A PubMed search of all English-language
      articles from January 1990 to January 2013 was conducted using the search terms
      depression and 5-HT 1A, depression and buspirone, depression and pindolol, and
      vilazodone. STUDY SELECTION: We found 47 articles and abstracts that were
      selected for inclusion on the basis of information about the pharmacology of 5
      HT1A receptors and the clinical data on pindolol, buspirone, and vilazodone in
      depression. DATA EXTRACTION: This review summarizes current literature involving
      antidepressant activity, the role of 5-HT1A autoreceptors, and clinical trials
      involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and
      partial agonists, with a focus on vilazodone. RESULTS: Vilazodone has
      demonstrated efficacy in 2 large, randomized, double-blind, placebo-controlled
      trials in major depressive disorder. RESULTS suggest that vilazodone has a low
      incidence of sexual side effects and is effective in patients with high levels of
      anxiety. A pooled analysis shows evidence of significant symptom reduction after
      only 1 week of therapy. CONCLUSIONS: If future studies corroborate the clinical
      benefits attributed to its mechanism of action, vilazodone may show potential
      advantages in terms of onset of action, sexual side effects, and anxiolytic
      activity in patients with major depressive disorder.

PMID- 24940530
TI  - Sociodemographic Disparities in Quality of Life for Survivors of Adolescent and
      Young Adult Cancers in the Behavioral Risk Factor Surveillance System.
AB  - Purpose: Survivors of cancer diagnosed during adolescence and young adulthood
      (AYA; aged 15-39) may experience quality of life (QOL) limitations; however,
      little is known about QOL for AYA survivors who are now middle-aged or among
      racial/ethnic minority survivors. We evaluated QOL outcomes for AYA cancer
      survivors relative to a non-cancer comparison group by gender, race/ethnicity,
      and current age. Methods: Using the 2009 Behavioral Risk Factor Surveillance
      System (BRFSS) data, we identified 8375 individuals diagnosed with cancer while
      aged 15-39 years old and 334,759 controls. Participants were currently >=20 years
      of age. QOL was measured using four items from the Center for Disease Control's
      Healthy Days Measure (general health, number of days of poor physical and mental
      health, and activity limitation days). Multivariable regressions compared these
      measures for survivors and controls by gender, race/ethnicity, and age, and among
      survivors to determine cancer-related factors associated with poor QOL. Results:
      Survivors were more likely to report fair/poor general health than controls
      (relative risk=1.92; 95% confidence interval: 1.77-2.10; p<0.001). QOL
      limitations existed by gender and race/ethnicity for survivors. Approximately 30%
      of survivors currently in their 40s, 50s, and early 60s were in poor health,
      compared to less than 20% of same-aged controls (both p<0.001). Of survivors with
      two or more cancers, 41.0% reported poor health, compared to 26.2% with one
      cancer (p<0.001). Conclusion: AYA cancer survivors have worse QOL compared to the
      general population and these limitations persist across gender, race/ethnicity,
      and age. Targeted interventions are essential for improving AYA cancer survivors'
      health status.

PMID- 24940531
TI  - Fertility Preservation Preferences and Perspectives Among Adult Male Survivors of
      Pediatric Cancer and Their Parents.
AB  - Purpose: In this study, we set out to determine the preferences, concerns, and
      attitudes toward fertility preservation of adult male survivors of pediatric
      cancer and their parents. Methods: We conducted 3 focus groups with a total of 15
      male survivors of pediatric cancer (age at diagnosis: mean=14, range: 10-20; age
      at study: mean=35, range: 25-47) and 2 groups with a total of 7 parents of
      survivors. Grounded theory methodology was used for the identification and
      analysis of recurrent themes expressed by survivors and their parents in the
      course of focus group discussions. Results: Themes most frequently expressed by
      survivors included concern regarding long-term treatment effects and a
      retrospective desire for fertility impairment to have been discussed when they
      were originally diagnosed with cancer. Parental themes included the same
      hindsight desire, as well as reliance upon the treating oncologist for direction
      in selecting the course of treatment, and an acknowledgment that input from a
      specialist in fertility preservation would have been beneficial. Conclusions:
      Although future reproductive potential was not consistently reported as a source
      of apprehension when diagnosed with cancer, both survivors and their parents
      noted it to be a paramount concern later in life. Parents and survivors both
      reported that fertility preservation discussions should be routinely incorporated
      in the clinical context of a pediatric cancer diagnosis.

PMID- 24940532
TI  - Preserving Fertility in Adolescent Girls and Young Women Requiring Craniospinal
      Irradiation: A Case Report and Discussion of Options to Be Considered Prior to
      Treatment.
AB  - Craniospinal irradiation (CSI) is associated with infertility risk for
      adolescent/young adult women. We explore two methods of reducing ovarian
      exposure: oophoropexy (surgical removal of the ovaries from the path of the X-ray
      beam) and proton therapy (to allow the beam to stop without exposing the
      ovaries/uterus). In the case discussed, oophoropexy followed by X-ray CSI reduced
      ovarian dose to that at which 50% of oocytes are expected to survive, and the
      patient appears to have viable oocytes; this technique did not reduce uterine
      dose. Proton therapy would have eliminated the ovarian and uterine dose and the
      need for oophoropexy.

PMID- 24940533
TI  - In vivo two-photon microscopy of the hippocampus using glass plugs.
AB  - Two-photon microscopy has been used in conjunction with micro-optics, such as
      GRIN lenses, to access subcortical structures in the intact mouse brain. In this
      study, we demonstrate the use of thick glass windows, or plugs, for high
      resolution, large field-of-view two-photon imaging of the hippocampus in a live
      mouse. These plugs are less expensive, yield larger fields-of-view and are
      simpler to use than GRIN lenses while requiring less tissue removal compared to
      previous methods based on cortical ablation. To demonstrate the capabilities of
      our system, we show fluorescence images of dendritic spines in the CA1 region of
      the hippocampus in THY1-YFP transgenic mice. 

PMID- 24940534
TI  - Modulated-alignment dual-axis (MAD) confocal microscopy for deep optical
      sectioning in tissues.
AB  - A strategy is presented to enable optical-sectioning microscopy with improved
      contrast and imaging depth using low-power (0.5 - 1 mW) diode laser illumination.
      This technology combines the inherent strengths of focal-modulation microscopy
      and dual-axis confocal (DAC) microscopy for rejecting out-of-focus and multiply
      scattered background light in tissues. The DAC architecture is unique in that it
      utilizes an intersecting pair of illumination and collection beams to improve the
      spatial-filtering and optical-sectioning performance of confocal microscopy while
      focal modulation selectively 'labels' in-focus signals via amplitude modulation.
      Simulations indicate that modulating the spatial alignment of dual-axis beams at
      a frequency f generates signals from the focal volume of the microscope that are
      modulated at 2f with minimal modulation of background signals, thus providing
      nearly an order-of-magnitude improvement in optical-sectioning contrast compared
      to DAC microscopy alone. Experiments show that 2f lock-in detection enhances
      contrast and imaging depth within scattering phantoms and fresh tissues. 

PMID- 24940535
TI  - Off-axis digital holographic camera for quantitative phase microscopy.
AB  - We propose and experimentally demonstrate a digital holographic camera which can
      be attached to the camera port of a conventional microscope for obtaining digital
      holograms in a self-reference configuration, under short coherence illumination
      and in a single shot. A thick holographic grating filters the beam containing the
      sample information in two dimensions through diffraction. The filtered beam
      creates the reference arm of the interferometer. The spatial filtering method,
      based on the high angular selectivity of the thick grating, reduces the alignment
      sensitivity to angular displacements compared with pinhole based Fourier
      filtering. The addition of a thin holographic grating alters the coherence plane
      tilt introduced by the thick grating so as to create high-visibility interference
      over the entire field of view. The acquired full-field off-axis holograms are
      processed to retrieve the amplitude and phase information of the sample. The
      system produces phase images of cheek cells qualitatively similar to phase images
      extracted with a standard commercial DHM. 

PMID- 24940537
TI  - Detection limits of confocal surface plasmon microscopy.
AB  - This paper applies rigorous diffraction theory to evaluate the minimum mass
      sensitivity of a confocal optical microscope designed to excite and detect
      surface plasmons operating on a planar metallic substrate. The diffraction model
      is compared with an intuitive ray picture which gives remarkably similar
      predictions. The combination of focusing the surface plasmons and accurate phase
      measurement mean that under favorable but achievable conditions detection of
      small numbers of molecules is possible, however, we argue that reliable detection
      of single molecules will benefit from the use of structured surfaces. System
      configurations needed to optimize performance are discussed. 

PMID- 24940538
TI  - Spectral multiplexing and coherent-state decomposition in Fourier ptychographic
      imaging.
AB  - Information multiplexing is important for biomedical imaging and chemical
      sensing. In this paper, we report a microscopy imaging technique, termed state
      multiplexed Fourier ptychography (FP), for information multiplexing and coherent
      state decomposition. Similar to a typical Fourier ptychographic setting, we use
      an array of light sources to illuminate the sample from different incident angles
      and acquire corresponding low-resolution images using a monochromatic camera. In
      the reported technique, however, multiple light sources are lit up simultaneously
      for information multiplexing, and the acquired images thus represent incoherent
      summations of the sample transmission profiles corresponding to different
      coherent states. We show that, by using the state-multiplexed FP recovery
      routine, we can decompose the incoherent mixture of the FP acquisitions to
      recover a high-resolution sample image. We also show that, color-multiplexed
      imaging can be performed by simultaneously turning on R/G/B LEDs for data
      acquisition. The reported technique may provide a solution for handling the
      partially coherent effect of light sources used in Fourier ptychographic imaging
      platforms. It can also be used to replace spectral filter, gratings or other
      optical components for spectral multiplexing and demultiplexing. With the
      availability of cost-effective broadband LEDs, the reported technique may open up
      exciting opportunities for computational multispectral imaging. 

PMID- 24940536
TI  - In vivo imaging of nanoparticle delivery and tumor microvasculature with
      multimodal optical coherence tomography.
AB  - Current imaging techniques capable of tracking nanoparticles in vivo supply
      either a large field of view or cellular resolution, but not both. Here, we
      demonstrate a multimodality imaging platform of optical coherence tomography
      (OCT) techniques for high resolution, wide field of view in vivo imaging of
      nanoparticles. This platform includes the first in vivo images of nanoparticle
      pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying
      images of microvascular and tissue morphology. Gold nanorods (51.8 +/- 8.1 nm by
      15.2 +/- 3.3 nm) were intravenously injected into mice, and their accumulation
      into mammary tumors was non-invasively imaged in vivo in three dimensions over 24
      hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold
      nanorods reached peak distribution throughout the tumors by 16 hours, and
      remained well-dispersed up to 24 hours post-injection. In contrast, the overall
      accumulation of gold nanorods within the tumors peaked around 16 hours post
      injection. The accumulation of gold nanorods within the tumors was validated post
      mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a
      powerful multimodality imaging platform for the development of nanomedicines and
      drug delivery technologies. 

PMID- 24940539
TI  - Wavefront sensorless adaptive optics temporal focusing-based multiphoton
      microscopy.
AB  - Temporal profile distortions reduce excitation efficiency and image quality in
      temporal focusing-based multiphoton microscopy. In order to compensate the
      distortions, a wavefront sensorless adaptive optics system (AOS) was integrated
      into the microscope. The feedback control signal of the AOS was acquired from
      local image intensity maximization via a hill-climbing algorithm. The control
      signal was then utilized to drive a deformable mirror in such a way as to
      eliminate the distortions. With the AOS correction, not only is the axial
      excitation symmetrically refocused, but the axial resolution with full two-photon
      excited fluorescence (TPEF) intensity is also maintained. Hence, the contrast of
      the TPEF image of a R6G-doped PMMA thin film is enhanced along with a 3.7-fold
      increase in intensity. Furthermore, the TPEF image quality of 1MUm fluorescent
      beads sealed in agarose gel at different depths is improved. 

PMID- 24940541
TI  - Fiber-optic chirped FBG for distributed thermal monitoring of ex-vivo
      radiofrequency ablation of liver.
AB  - A linearly chirped fiber Bragg grating (LCFBG) has been used as a temperature
      sensor for online monitoring of radiofrequency thermal ablation (RFTA). The LCFBG
      acts as a distributed sensor, with spatial resolution of 75 MUm. A white-light
      setup that records the LCFBG spectrum estimates the temperature profile in real
      time. Three RFTA experiments have been performed ex-vivo on porcine liver
      measuring the radial temperature distribution during the heating process. The
      analysis of thermal maps quantifies the spatial heat distribution along the
      measurement axis and determines the ablation efficiency. 

PMID- 24940540
TI  - State-space models of impulse hemodynamic responses over motor, somatosensory,
      and visual cortices.
AB  - THE PAPER PRESENTS STATE SPACE MODELS OF THE HEMODYNAMIC RESPONSE (HR) OF FNIRS
      TO AN IMPULSE STIMULUS IN THREE BRAIN REGIONS: motor cortex (MC), somatosensory
      cortex (SC), and visual cortex (VC). Nineteen healthy subjects were examined. For
      each cortex, three impulse HRs experimentally obtained were averaged. The
      averaged signal was converted to a state space equation by using the subspace
      method. The activation peak and the undershoot peak of the oxy-hemoglobin (HbO)
      in MC are noticeably higher than those in SC and VC. The time-to-peaks of the HbO
      in three brain regions are almost the same (about 6.76 76 +/- 0.2 s). The time to
      undershoot peak in VC is the largest among three. The HbO decreases in the early
      stage (~0.46 s) in MC and VC, but it is not so in SC. These findings were well
      described with the developed state space equations. Another advantage of the
      proposed method is its easy applicability in generating the expected HR to
      arbitrary stimuli in an online (or real-time) imaging. Experimental results are
      demonstrated. 

PMID- 24940542
TI  - Hemodynamic responses in rat brain during transcranial direct current
      stimulation: a functional near-infrared spectroscopy study.
AB  - In the present study, we monitored hemodynamic responses in rat brains during
      transcranial direct current stimulation (tDCS) using functional near-infrared
      spectroscopy (fNIRS). Seven rats received transcranial anodal stimulation with
      200 MUA direct current (DC) on their right barrel cortex for 10 min. The
      concentration changes of oxygenated hemoglobin (oxy-Hb) were continuously
      monitored during stimulation (10 min) and after stimulation (20 min). The trend
      of hemodynamic response changes was modeled using linear regression, and the
      relationship between incremental and decremental rates of oxy-Hb was investigated
      by correlation analysis. Our results showed that the oxy-Hb concentration was
      almost linearly increased and decreased during and after stimulation,
      respectively. In addition, a significant negative correlation (p < 0.05) was
      found between the rate of increase of oxy-Hb during stimulation and the rate of
      decrease of oxy-Hb after stimulation, indicating that the recovery time after
      tDCS may not depend on the total amount of hemodynamic changes in the stimulated
      brain area. Our results also demonstrated considerable individual variability in
      the rate of change of hemodynamic responses even with the same direct current
      dose to identical brain regions. This suggests that individual differences in
      tDCS after-effects may originate from intrinsic differences in the speed of DC
      stimulation "uptake" rather than differences in the total capacity of DC uptake,
      and thus the stimulation parameters may need to be customized for each individual
      in order to maximize tDCS after-effects. 

PMID- 24940543
TI  - Image simulation for biological microscopy: microlith.
AB  - Image simulation remains under-exploited for the most widely used biological
      phase microscopy methods, because of difficulties in simulating partially
      coherent illumination. We describe an open-source toolbox, microlith
      (https://code.google.com/p/microlith), which accurately predicts three
      dimensional images of a thin specimen observed with any partially coherent
      imaging system, as well as images of coherently illuminated and self-luminous
      incoherent specimens. Its accuracy is demonstrated by comparing simulated and
      experimental bright-field and dark-field images of well-characterized amplitude
      and phase targets, respectively. The comparison provides new insights about the
      sensitivity of the dark-field microscope to mass distributions in isolated or
      periodic specimens at the length-scale of 10nm. Based on predictions using
      microlith, we propose a novel approach for detecting nanoscale structural changes
      in a beating axoneme using a dark-field microscope. 

PMID- 24940544
TI  - Reconstruction of localized fluorescent target from multi-view continuous-wave
      surface images of small animal with lp sparsity regularization.
AB  - Fluorescence diffuse optical tomography using a multi-view continuous-wave and
      non-contact measurement system and an algorithm incorporating the lp (0 < p <= 1)
      sparsity regularization reconstructs a localized fluorescent target in a small
      animal. The measurement system provides a total of 25 fluorescence surface 2D
      images of an object, which are acquired by a CCD camera from five different
      angles of view with excitation from five different angles. Fluorescence surface
      emissions from five different angles of view are simultaneously imaged on the CCD
      sensor, thus leading to fast acquisition of the 25 images within three minutes.
      The distributions of the fluorophore are reconstructed by solving the inverse
      problem based on the photon diffusion equations. In the reconstruction process
      incorporating the lp sparsity regularization, the regularization term is
      reformulated as a differentiable function for gradient-based non-linear
      optimization. Numerical simulations and phantom experiments show that the use of
      the lp sparsity regularization improves the localization of the target and
      quantitativeness of the fluorophore concentration. A mouse experiment
      demonstrates that a localized fluorescent target in a mouse is successfully
      reconstructed. 

PMID- 24940545
TI  - Incorporating MRI structural information into bioluminescence tomography: system,
      heterogeneous reconstruction and in vivo quantification.
AB  - Combining two or more imaging modalities to provide complementary information has
      become commonplace in clinical practice and in preclinical and basic biomedical
      research. By incorporating the structural information provided by computed
      tomography (CT) or magnetic resonance imaging (MRI), the ill poseness nature of
      bioluminescence tomography (BLT) can be reduced significantly, thus improve the
      accuracies of reconstruction and in vivo quantification. In this paper, we
      present a small animal imaging system combining multi-view and multi-spectral BLT
      with MRI. The independent MRI-compatible optical device is placed at the end of
      the clinical MRI scanner. The small animal is transferred between the light tight
      chamber of the optical device and the animal coil of MRI via a guide rail during
      the experiment. After the optical imaging and MRI scanning procedures are
      finished, the optical images are mapped onto the MRI surface by interactive
      registration between boundary of optical images and silhouette of MRI. Then,
      incorporating the MRI structural information, a heterogeneous reconstruction
      algorithm based on finite element method (FEM) with L 1 normalization is used to
      reconstruct the position, power and region of the light source. In order to
      validate the feasibility of the system, we conducted experiments of nude mice
      model implanted with artificial light source and quantitative analysis of tumor
      inoculation model with MDA-231-GFP-luc. Preliminary results suggest the
      feasibility and effectiveness of the prototype system. 

PMID- 24940546
TI  - Microscope-integrated intraoperative OCT with electrically tunable focus and
      heads-up display for imaging of ophthalmic surgical maneuvers.
AB  - We present novel optical and mechanical designs for a microscope-integrated
      intraoperative optical coherence tomography (iOCT) system with enhanced function
      and ergonomics for visualization of ophthalmic surgical maneuvers. Integration of
      an electrically tunable lens allows rapid focal plane adjustment and iOCT imaging
      of both anterior and posterior segment tissue microstructures while maintaining
      parfocality with the ophthalmic surgical microscope. We demonstrate novel
      visualization of instrument positions relative to tissue layers of interest as
      colormap overlays onto en face OCT data, which may provide integrative display of
      volumetric information during surgical maneuvers. Finally, we implement a heads
      up display system to provide real-time feedback as proof-of-principle for iOCT
      guided ophthalmic surgery. 

PMID- 24940547
TI  - Double nanohole optical tweezers visualize protein p53 suppressing unzipping of
      single DNA-hairpins.
AB  - Here we report on the use of double-nanohole (DNH) optical tweezers as a label
      free and free-solution single-molecule probe for protein-DNA interactions. Using
      this approach, we demonstrate the unzipping of individual 10 base pair DNA
      hairpins, and quantify how tumor suppressor p53 protein delays the unzipping.
      From the Arrhenius behavior, we find the energy barrier to unzipping introduced
      by p53 to be 2 * 10(-20) J, whereas cys135ser mutant p53 does not show
      suppression of unzipping, which gives clues to its functional inability to
      suppress tumor growth. This transformative approach to single molecule analysis
      allows for ultra-sensitive detection and quantification of protein-DNA
      interactions to revolutionize the fight against genetic diseases. 

PMID- 24940548
TI  - Enhancing the isotropy of lateral resolution in coherent structured illumination
      microscopy.
AB  - We present a method to improve the isotropy of spatial resolution in a structured
      illumination microscopy (SIM) implemented for imaging non-fluorescent samples. To
      alleviate the problem of anisotropic resolution involved with the previous scheme
      of coherent SIM that employs the two orthogonal standing-wave illumination,
      referred to as the orthogonal SIM, we introduce a hexagonal-lattice illumination
      that incorporates three standing-wave fields simultaneously superimposed at the
      orientations equally divided in the lateral plane. A theoretical formulation is
      worked out rigorously for the coherent image formation with such a simultaneous
      multiple-beam illumination and an explicit Fourier-domain framework is derived
      for reconstructing an image with enhanced resolution. Using a computer
      synthesized resolution target as a 2D coherent sample, we perform numerical
      simulations to examine the imaging characteristics of our three-angle SIM
      compared with the orthogonal SIM. The investigation on the 2D resolving power
      with the various test patterns of different periods and orientations reveal that
      the orientation-dependent undulation of lateral resolution can be reduced from
      27% to 8% by using the three-angle SIM while the best resolution (0.54 times the
      resolution limit of conventional coherent imaging) in the directions of
      structured illumination is slightly deteriorated by 4.6% from that of the
      orthogonal SIM. 

PMID- 24940549
TI  - Extraction of intrinsic fluorescence from single fiber fluorescence measurements
      on a turbid medium: experimental validation.
AB  - The detailed mechanisms associated with the influence of scattering and
      absorption properties on the fluorescence intensity sampled by a single optical
      fiber have recently been elucidated based on Monte Carlo simulated data. Here we
      develop an experimental single fiber fluorescence (SFF) spectroscopy setup and
      validate the Monte Carlo data and semi-empirical model equation that describes
      the SFF signal as a function of scattering. We present a calibration procedure
      that corrects the SFF signal for all system-related, wavelength dependent
      transmission efficiencies to yield an absolute value of intrinsic fluorescence.
      The validity of the Monte Carlo data and semi-empirical model is demonstrated
      using a set of fluorescent phantoms with varying concentrations of Intralipid to
      vary the scattering properties, yielding a wide range of reduced scattering
      coefficients (MU's = 0-7 mm (-1)). We also introduce a small modification to the
      model to account for the case of MU's = 0 mm (-1) and show its relation to the
      experimental, simulated and theoretically calculated value of SFF intensity in
      the absence of scattering. Finally, we show that our method is also accurate in
      the presence of absorbers by performing measurements on phantoms containing red
      blood cells and correcting for their absorption properties. 

PMID- 24940550
TI  - Improved noncontact optical sensor for detection of glucose concentration and
      indication of dehydration level.
AB  - The ability to extract different bio-medical parameters from one single
      wristwatch device can be very applicable. The wearable device that is presented
      in this paper is based on two optical approaches. The first is the extraction and
      separation of remote vibration sources and the second is the rotation of linearly
      polarized light by certain materials exposed to magnetic fields. The technique is
      based on tracking of temporal changes of reflected secondary speckles produced in
      the wrist when being illuminated by a laser beam. Change in skin's temporal
      vibration profile together with change in the magnetic medium that is generated
      by time varied glucose concentration caused these temporal changes. In this paper
      we present experimental tests which are the first step towards an in vivo
      noncontact device for detection of glucose concentration in blood. The paper also
      shows very preliminary results for qualitative capability for indication of
      dehydration. 

PMID- 24940551
TI  - Registration of adaptive optics corrected retinal nerve fiber layer (RNFL)
      images.
AB  - Glaucoma is the leading cause of preventable blindness in the western world.
      Investigation of high-resolution retinal nerve fiber layer (RNFL) images in
      patients may lead to new indicators of its onset. Adaptive optics (AO) can
      provide diffraction-limited images of the retina, providing new opportunities for
      earlier detection of neuroretinal pathologies. However, precise processing is
      required to correct for three effects in sequences of AO-assisted, flood
      illumination images: uneven illumination, residual image motion and image
      rotation. This processing can be challenging for images of the RNFL due to their
      low contrast and lack of clearly noticeable features. Here we develop specific
      processing techniques and show that their application leads to improved image
      quality on the nerve fiber bundles. This in turn improves the reliability of
      measures of fiber texture such as the correlation of Gray-Level Co-occurrence
      Matrix (GLCM). 

PMID- 24940552
TI  - Visualization of upconverting nanoparticles in strongly scattering media.
AB  - Optical visualization systems are needed in medical applications for determining
      the localization of deep-seated luminescent markers in biotissues. The spatial
      resolution of such systems is limited by the scattering of the tissues. We
      present a novel epi-luminescent technique, which allows a 1.8-fold increase in
      the lateral spatial resolution in determining the localization of markers lying
      deep in a scattering medium compared to the traditional visualization techniques.
      This goal is attained by using NaYF4:Yb(3+)Tm(3+)@NaYF4 core/shell nanoparticles
      and special optical fiber probe with combined channels for the excitation and
      detection of anti-Stokes luminescence signals. 

PMID- 24940553
TI  - In vivo spectral and fluorescence microscopy comparison of microvascular function
      after treatment with OXi4503, Sunitinib and their combination in Caki-2 tumors.
AB  - Vascular targeting agents on their own have been shown to be insufficient for
      complete treatment of solid tumors, emphasizing the importance of studying the
      vascular effects of these drugs for their use with conventional therapies in the
      clinic. First-pass fluorescence imaging combined with hyperspectral imaging of
      hemoglobin saturation of microvessels in the murine dorsal window chamber model
      provides an easily implementable, low cost method to analyze tumor vascular
      response to these agents in real-time. In this study, the authors utilized these
      methods to spectroscopically demonstrate distinct vessel structure, blood flow
      and oxygenation changes in human Caki-2 renal cell carcinoma following treatment
      with OXi4503 alone, Sunitinib alone and both drugs together. We showed that
      treatment with OXi4503 plus Sunitinib destroyed existing tumor microvessels,
      inhibited blood vessel recovery and impaired Caki-2 tumor growth significantly
      more than either treatment alone. 

PMID- 24940554
TI  - The Effect of Bone-Marrow-Derived Stem Cells and Adipose-Derived Stem Cells on
      Wound Contraction and Epithelization.
AB  - Objective: The relationship between the wound contraction and levels of alpha
      smooth muscle actin (alpha-SMA) has been revealed in different studies. We aimed
      to investigate the effects of mesenchymal stem cells (MSCs), mainly bone-marrow
      derived stem cells (BSCs) and adipose-derived stem cells (ASCs), and find out the
      alpha-SMA, fibroblast growth factor (FGF), transforming growth factor beta, and
      vascular endothelial growth factor (VEGF) levels on an in vivo acute wound
      healing model after the application of MSCs. Approach: Four circular skin defects
      were formed on the dorsum of Fisher rats (n=20). The defects were applied
      phosphate-buffered saline (PBS), ASCs, BSCs, and patchy skin graft, respectively.
      The healing time and scar area were noted. Results: There was a statistical
      decrease in the healing time in ASC, BSC, and skin graft groups (p<0.05).
      However, the scar was smaller in the PBS group (p<0.05). The alpha-SMA levels
      were statistically lower in ASC, BSC, and graft groups (p<0.05). The FGF levels
      were statistically higher in ASC and BSC groups (p<0.05). The differentiation of
      the injected MSCs to endothelial cells and keratinocytes was observed. Innovation
      and Conclusion: MSCs decrease the healing time and contraction of the wound while
      increasing the epithelization rate by increasing angiogenesis.

PMID- 24940555
TI  - Factors Influencing Efficacy of Bilayered Cell Therapy.
AB  - Objective: Diabetic foot ulcers (DFUs) that fail to heal with standard care
      should be treated with advanced wound care products. Efficacy of advanced
      therapies is dependent on many factors. A secondary analysis of pivotal trial
      data for a bilayered cellular construct used in the treatment of DFU was
      undertaken to determine if glycemic control and other factors had an effect on
      time to healing. Approach: We analyzed the effect of age, gender, diabetes type,
      insulin usage, body mass index, smoking, initial and ending glycohemoglobin
      (HgbA1c), Charcot deformity, and wound area, duration, and location on likelihood
      of healing for wounds treated with bilayered cellular construct (BLCC). Results:
      In those treated with BLCC, initial wound area (cm2), age, and history of Charcot
      deformity were found to significantly affect healing. Neither initial HgbA1c nor
      change in HgbA1c was associated with healing. The bilayered product was found to
      be equally effective regardless of initial or change in HgbA1c levels (p-values
      0.94 and 0.44, respectively). In the control group, initial HgbA1c, insulin
      usage, female gender, and wound location at the toes significantly influenced
      healing. Innovation: BLCC subgroup analysis to elucidate selection criteria
      allowing for targeted use of advanced products on those more likely to respond as
      well as direct further research into prognostic indicators for BLCC-treated
      patients. Conclusion: The bilayered cellular construct product remains equally
      effective regardless of initial or change in HgbA1c levels. Further specific
      research into the effect of glucose control and other factors on the
      effectiveness of different advanced DFU treatment products is recommended.

PMID- 24940556
TI  - Topical Naltrexone as Treatment for Type 2 Diabetic Cutaneous Wounds.
AB  - Objective: Type 2 diabetes (T2D) is associated with impaired cutaneous wound
      healing and can result in ulceration, infection, and/or amputation. More than 25
      million people in the United States have T2D and are vulnerable to epithelial
      related complications. Current therapies are limited in their efficacy. New
      treatments for full-thickness cutaneous wounds that focus on underlying diabetic
      pathways are needed. Approach: Topical application of the opioid receptor
      antagonist naltrexone (NTX) dissolved in cream reverses delayed wound closure in
      type 1 diabetic rat by the acceleration of reepithelialization and enhancement of
      angiogenesis and remodeling. NTX blocks the opioid growth factor (OGF)-OGF
      receptor (OGFr) axis and upregulates DNA synthesis and cell proliferation. To
      investigate whether NTX is an effective therapy for T2D wound closure,
      genetically obese mice (db/db) and normal C57Bl/6J mice received full-thickness
      cutaneous wounds. Wounds (5 mm in diameter) were treated topically three times
      daily with 10-5 M NTX or sterile saline dissolved in cream and photographed every
      2 days. Results: Wounds in db/db mice treated with saline were 11-92% larger than
      those in normal mice throughout the 2-week observation. Topical NTX therapy in
      T2D mice reduced the residual wound size by 13-30% between days 8 and 14 relative
      to diabetic mice receiving saline. Reepithelialization and DNA synthesis, as
      analyzed by epithelial thickness and BrdU labeling indexes, respectively, were
      accelerated in NTX-treated wounds. Innovation and Conclusion: These data suggest
      that the OGF-OGFr axis plays a role in epithelial-related complications of T2D
      and that blockade of this pathway by NTX may be an effective treatment for wound
      repair.

PMID- 24940557
TI  - Systemic Evaluation of Electrical Stimulation for Ischemic Wound Therapy in a
      Preclinical In Vivo Model.
AB  - Objective: In a systematic preclinical investigation of ischemic wound healing,
      we investigated the hypothesis that electrical stimulation (ES) promotes the
      healing of ischemic wounds. Approach: The effects of varying clinically relevant
      ES variables were evaluated using our modified version of the Gould F344 rat
      ischemic wound model. Stimulation was delivered using the novel lightweight
      integrated, single-channel, current-controlled modular surface stimulation (MSS)
      device. Stepwise variation allowed the effects of five different stimulation
      paradigms within an appropriate current density range to be studied. Within each
      group, 8-10 animals were treated for 28 days or until the ischemic wounds were
      healed and 5 animals were treated for 12 days. Eight rats received sham devices.
      A quantitative multivariable outcomes assessment procedure was used to evaluate
      the effects of ES. Results: Ischemic wounds treated with a decreased interpulse
      interval (IPI) had the highest rate of complete wound closure at 3 weeks. Wounds
      treated with decreased pulse amplitude (PA) had a lower proportion of closed
      wounds than sham ischemic wounds and showed sustained inflammation with a lack of
      wound contraction. Innovation: Our systematic study of varying ES paradigms using
      the novel MSS device provides preliminary insight into potential mechanisms of ES
      in ischemic wound healing. Conclusion: Clinically appropriate ES can more than
      double the proportion of ischemic wounds closed by 3 weeks in this model. Ninety
      percent of wounds treated with a decreased IPI healed by 21 days compared with
      only 29% of ischemic wounds treated with decreased PA, which appears to inhibit
      healing.

PMID- 24940558
TI  - Assessment of the Size of the Surgical Site in Minimally Invasive Hip Surgery.
AB  - Objective: Minimally invasive approaches to the hip are beneficial to the
      patient, but reduce the space available for manipulation by the surgeon.
      Determining the available working space is important for the development of
      surgical instruments, to track movements during surgery, as well as to classify
      the invasiveness of the procedure. Approach: We evaluate three measurement
      methods to assess the volume of eight surgical sites in a cadaver study. The
      cavities were filled with an alginate cast to determine its dimensions. Second,
      the depth, height, and width of the surgical site were measured with a ruler and
      the volume was calculated. Last, the surface registration method was used to
      reconstruct the site. Results: We found that the mold filling method provides
      accurate results in determining the volume of a surgical site. The manual method
      using a ruler showed excellent reliability, but the calculations tended to
      overestimate the volume of the surgical site. In contrast, surface reconstruction
      tended to underestimate the volume of a surgical site, but the results closer
      resembled the ones derived from the mold filling method. Innovation: We presented
      a new method to assess the size of the surgical site intraoperatively in
      minimally invasive hip surgery. Conclusion: The manual method is reliable, but
      not as accurate as the surface reconstruction, while the mold filling method
      cannot be used in an intraoperative setup. Although surface reconstruction showed
      deficits regarding reliability, due to the lack of direct contact to the patient,
      it remains an appealing technique to measure the surgical site.

PMID- 24940559
TI  - An in vitro culture system that supports robust expansion and maintenance of in
      vivo engraftment capabilities for myogenic progenitor cells from adult mice.
AB  - Muscle cell therapy and tissue engineering require large numbers of functional
      muscle precursor/progenitor cells (MPCs), making the in vitro expansion of MPCs a
      critical step for these applications. The cells must maintain their myogenic
      properties upon robust expansion, especially for cellular therapy applications,
      in order to achieve efficacious treatment. A major obstacle associated with MPCs
      expansion is the loss of "stemness," or regenerative capacity, of freshly
      isolated cells, presumably due to the absence of the native cellular niches. In
      the current study, we developed an in vitro system that allowed for long-term
      culture and massive expansion of murine MPCs (mMPCs) with the preservation of
      myogenic regeneration capabilities. Long term in vitro expanded mMPC expressed
      the myogenic stem cell markers Pax3 and Pax7 and formed spontaneously contracting
      myotubes. Furthermore, expanded mMPC injected into the tibialis anterior muscle
      of nude mice engrafted and formed myofibers. Collectively, the method developed
      in this study can be potentially adapted for the expansion of human MPCs to high
      enough numbers for treatment of muscle injuries in human patients. 

PMID- 24940560
TI  - Spiral ganglion stem cells can be propagated and differentiated into neurons and
      glia.
AB  - The spiral ganglion is an essential functional component of the peripheral
      auditory system. Most types of hearing loss are associated with spiral ganglion
      cell degeneration which is irreversible due to the inner ear's lack of
      regenerative capacity. Recent studies revealed the existence of stem cells in the
      postnatal spiral ganglion, which gives rise to the hope that these cells might be
      useful for regenerative inner ear therapies. Here, we provide an in-depth
      analysis of sphere-forming stem cells isolated from the spiral ganglion of
      postnatal mice. We show that spiral ganglion spheres have characteristics similar
      to neurospheres isolated from the brain. Importantly, spiral ganglion sphere
      cells maintain their major stem cell characteristics after repeated propagation,
      which enables the culture of spheres for an extended period of time. In this
      work, we also demonstrate that differentiated sphere-derived cell populations not
      only adopt the immunophenotype of mature spiral ganglion cells but also develop
      distinct ultrastructural features of neurons and glial cells. Thus, our work
      provides further evidence that self-renewing spiral ganglion stem cells might
      serve as a promising source for the regeneration of lost auditory neurons. 

PMID- 24940561
TI  - Endoderm complexity in the mouse gastrula is revealed through the expression of
      spink3.
AB  - Endoderm formation in the mammalian embryo occurs first in the blastocyst, when
      the primitive endoderm and pluripotent cells resolve into separate lineages, and
      again during gastrulation, when the definitive endoderm progenitor population
      emerges from the primitive streak. The formation of the definitive endoderm can
      be modeled using pluripotent cell differentiation in culture. The differentiation
      of early primitive ectoderm-like (EPL) cells, a pluripotent cell population
      formed from embryonic stem (ES) cells, was used to identify and characterize
      definitive endoderm formation. Expression of serine peptidase inhibitor, Kazal
      type 3 (Spink3) was detected in EPL cell-derived endoderm, and in a band of
      endoderm immediately distal to the embryonic-extra-embryonic boundary in
      pregastrula and gastrulating embryos. Later expression marked a region of
      endoderm separating the yolk sac from the developing gut. In the embryo, Spink3
      expression marked a region of endoderm comprising the distal visceral endoderm,
      as determined by an endocytosis assay, and the proximal region of the definitive
      endoderm. This region was distinct from the more distal definitive endoderm
      population, marked by thyrotropin-releasing hormone (Trh). Endoderm expressing
      either Spink3 or Trh could be formed during EPL cell differentiation, and the
      prevalence of these populations could be influenced by culture medium and growth
      factor addition. Moreover, further differentiation suggested that the potential
      of these populations differed. These approaches have revealed an unexpected
      complexity in the definitive endoderm lineage, a complexity that will need to be
      accommodated in differentiation protocols to ensure the formation of the
      appropriate definitive endoderm progenitor in the future. 

PMID- 24940562
TI  - Sustained Engraftment of Cryopreserved Human Bone Marrow CD34(+) Cells in Young
      Adult NSG Mice.
AB  - Hematopoietic stem cells (HSCs) are defined by their ability to repopulate the
      bone marrow of myeloablative conditioned and/or (lethally) irradiated recipients.
      To study the repopulating potential of human HSCs, murine models have been
      developed that rely on the use of immunodeficient mice that allow engraftment of
      human cells. The NSG xenograft model has emerged as the current standard for this
      purpose allowing for engraftment and study of human T cells. Here, we describe
      adaptations to the original NSG xenograft model that can be readily implemented.
      These adaptations encompass use of adult mice instead of newborns and a short ex
      vivo culture. This protocol results in robust and reproducible high levels of
      lympho-myeloid engraftment. Immunization of recipient mice with relevant antigen
      resulted in specific antibody formation, showing that both T cells and B cells
      were functional. In addition, bone marrow cells from primary recipients exhibited
      repopulating ability following transplantation into secondary recipients. Similar
      results were obtained with cryopreserved human bone marrow samples, thus
      circumventing the need for fresh cells and allowing the use of patient derived
      bio-bank samples. Our findings have implications for use of this model in
      fundamental stem cell research, immunological studies in vivo and preclinical
      evaluations for HSC transplantation, expansion, and genetic modification. 

PMID- 24940563
TI  - Surface Entrapment of Fibronectin on Electrospun PLGA Scaffolds for Periodontal
      Tissue Engineering.
AB  - Nowadays, the challenge in the tissue engineering field consists in the
      development of biomaterials designed to regenerate ad integrum damaged tissues.
      Despite the current use of bioresorbable polyesters such as poly(l-lactide)
      (PLA), poly(d,l-lactide-co-glycolide) (PLGA), and poly-E-caprolactone in soft
      tissue regeneration researches, their hydrophobic properties negatively influence
      the cell adhesion. Here, to overcome it, we have developed a fibronectin (FN)
      functionalized electrospun PLGA scaffold for periodontal ligament regeneration.
      Functionalization of electrospun PLGA scaffolds was performed by alkaline
      hydrolysis (0.1 or 0.01 M NaOH). Then, hydrolyzed scaffolds were coated by simple
      deposition of an FN layer (10 MUg/mL). FN coating was evidenced by X-ray
      photoelectron analysis. A decrease of contact angle and greater cell adhesion to
      hydrolyzed, FN-coated PLGA scaffolds were noticed. Suitable degradation behavior
      without pH variations was observed for all samples up to 28 days. All treated
      materials presented strong shrinkage, fiber orientation loss, and collapsed
      fibers. However, functionalization process using 0.01 M NaOH concentration
      resulted in unchanged scaffold porosity, preserved chemical composition, and
      similar mechanical properties compared with untreated scaffolds. The proposed
      simplified method to functionalize electrospun PLGA fibers is an efficient route
      to make polyester scaffolds more biocompatible and shows potential for tissue
      engineering. 

PMID- 24940564
TI  - Sorting of Sox1-GFP Mouse Embryonic Stem Cells Enhances Neuronal Identity
      Acquisition upon Factor-Free Monolayer Differentiation.
AB  - Embryonic stem cells (ESCs) can give rise to all the differentiated cell types of
      the organism, including neurons. However, the efficiency and specificity of
      neural differentiation protocols still needs to be improved in order to plan
      their use in cell replacement therapies. In this study, we modified a monolayer
      differentiation protocol by selecting green fluorescent protein (GFP) positive
      neural precursors with fluorescence-activated cell sorting (FACS). The
      enhancement of neural differentiation was obtained by positively selecting for
      neural precursors, while specific neuronal subtypes spontaneously differentiated
      without additional cues; a comparable but delayed behavior was also observed in
      the GFP negative population, indicating that sorting settings per se eliminated
      nonneural and undifferentiated ESCs. This highly reproducible approach could be
      applied as a strategy to enhance neuronal differentiation and could be the first
      step toward the selection of pure populations of neurons, to be generated by the
      administration of specific factors in high throughput screening assays. 

PMID- 24940565
TI  - A comparative study of broccoli sprouts powder and standard triple therapy on
      cardiovascular risk factors following H.pylori eradication: a randomized clinical
      trial in patients with type 2 diabetes.
AB  - BACKGROUND: In this clinical trial we compared the effects of broccoli sprouts
      powder, as an alternative and complementary treatment, to those of standard
      triple therapy, as a common medical treatment, on cardiovascular risk factors
      following the H.pylori eradication in patients with type 2 diabetes. METHODS:
      Eighty-six type 2 diabetic patients with positive H.pylori stool antigen test
      (HpSAg) were randomized to receive one of the three following regimens: STT)
      Standard triple therapy (omeprazole 20 mg, clarithromycin 500 mg, amoxicillin
      1000 mg, twice a day for 14 days), BSP) 6 g/d broccoli sprouts powder for 28
      days, and combination of these as STT + BSP. After 4 weeks of treatment, H.pylori
      eradication rates were assessed by HpSAg. Anthropometric measures, blood
      pressure, serum lipids and lipoproteins as well as serum high sensitive- C
      reactive protein were also assessed at baseline and at the second examination.
      RESULTS: Seventy-seven participants completed the study [STT (n = 28), BSP (n =
      25), STT + BSP (n = 24)]. The H.pylori eradication rates were 89.3%, 56.0% and
      91.7% in STT, BSP and STT + BSP groups, respectively. After the treatment, both
      systolic and diastolic blood pressure significantly decreased in STT + BSP group
      (P < 0.05). Serum triglycerides and TG/HDL-C ratio increased in STT patients
      group (<0.05). Serum hs-CRP levels significantly decreased in the patients who
      were treated with BSP per se (3.0 +/- 2.5 at baseline vs. 2.3 +/- 2.1 after the
      treatment, P < 0.05). CONCLUSION: Compared to standard triple therapy, BSP
      regimen in addition to considerable effects on H.pylori eradication had also
      favorable properties on cardiovascular risk factors following the H.pylori
      eradication.

PMID- 24940567
TI  - Into the night: factors affecting response to abnormal Early Warning Scores out
      of-hours and implications for service improvement.
AB  - BACKGROUND: Early Warning Scores alert staff to preventable deterioration. Raised
      scores should lead to escalation of care. AIMS: To establish response of staff to
      patients scoring National Early Warning Score (NEWS) of six or above and to
      identify patient and environmental factors affecting escalation by nursing staff.
      METHODS: Service evaluation with prospective review of patient records of 118
      beds on four medical wards during 20 night-shifts. RESULTS: During 2360 observed
      bed days 109 patients triggered NEWS>=6 at least once during the observation
      period. Nursing staff escalated only 18 (17%) of these patients; nearly all of
      them had predefined chronic health conditions, the majority fulfilled criteria
      for frailty. Despite their higher 30-day mortality patients with COPD had lower
      escalation rates. Additionally wards that had more patients with a NEWS>=6 had
      lower escalation rates. CONCLUSION: Alarm fatigue and clinical judgement of staff
      might result in deviation from escalation protocols.

PMID- 24940566
TI  - The association of family food security and depression in mothers having primary
      school children in Ray-Iran.
AB  - BACKGROUND: As a major public health problem, food insecurity has adverse social
      and psychological effects, in addition to the impact on public health. This study
      aimed to determine the association of household food security and depression in
      mothers with primary school children in Ray County. METHODS: This descriptive,
      analytical cross-sectional study was conducted on 430 mothers with primary school
      children in the spring 2010. During a two-stage cluster sampling, an 18-items
      food security questionnaire (USDA) and the Beck depression inventory were
      completed via interviewing mothers. Chi-squared test, one-way analysis of
      variance, simple regression and stepwise multiple regression were used to
      describe and analyze data, and to identify related factors using SPSS-16
      software. RESULTS: The prevalence of food insecurity and depression in mothers
      were 50.2% and 51.4% respectively. Also 34.6% of mothers in the "food secure"
      group were depressed and 77.8% in "food insecure with hunger" group were
      depressed and this difference was statistically significant. Twelve out of the 20
      examined variables (age, family size, number of children, economic status, home
      ownership, employment households, educational level of the mother and also the
      head of household, height, energy intake, and carbohydrate and protein intakes)
      were significantly associated with food security and depression. Food insecurity
      and depression in mothers with primary school children in Ray County showed a
      significant positive correlation (P < 0.001). CONCLUSION: The prevalence of
      household food insecurity and depression in the studied population were high.
      Since there is a significant relationship between food insecurity and depression,
      more attention must be paid to this group.

PMID- 24940568
TI  - Pause for thought? Syncope and sinus arrest as the presenting feature of temporal
      lobe epilepsy.
AB  - Some forms of focal epilepsy, including temporal lobe epilepsy, are rarely
      associated with ictal bradycardia and sinus node arrest. We report a case of a
      previously healthy man presenting with syncope in whom telemetry revealed sinus
      arrest. Initial treatment was with permanent pacemaker implantation and it was
      only following a subsequent grand mal seizure that other symptoms suggestive of
      temporal lobe epilepsy were documented. Anti-epileptic medication was
      subsequently commenced with resolution of all symptoms. There are few previously
      reported cases of syncope and documented sinus node arrest as the presenting
      feature of temporal lobe epilepsy. 

PMID- 24940569
TI  - A giant cause of stroke.
AB  - An 80 year old man presented subacutely with drowsiness and confusion. Subsequent
      MRI brain imaging demonstrated multiple posterior circulation infarcts.
      Extracranial vasculitis was suspected when his ESR was found to be high and
      vascular imaging showed multifocal irregular narrowing of both vertebral
      arteries. This was confirmed by targeted temporal artery biopsy, which showed
      chronic granulomatous inflammation typical of giant cell arteritis (GCA). The
      patient made a significant recovery following treatment with prednisolone. 

PMID- 24940570
TI  - ST-segment elevation in patients with cocaine abuse and chest pain.
AB  - Use of cocaine may complicate the diagnosis of myocardial infarction (MI) and may
      influence treatment strategy. Patients with symptoms suggestive of acute coronary
      syndrome (ACS) should be questioned about the use of cocaine. Initial management
      of cocaine users presenting with chest pain and ST segment elevation should
      include administration of glyceryl trinitrate (GTN). Assessment for resolution of
      chest discomfort and ECG changes should be undertaken before fibrinolytic therapy
      or angiography is considered. We present a case of patient with chest pain (CP)
      and ST elevation after cocaine use, whose symptoms and ST changes promptly
      resolved after medical therapy. Our case highlights the importance of medical
      therapy in patient with CP and ST elevation after cocaine abuse, before
      activating cardiac catheterization laboratory for emergent angiography. 

PMID- 24940571
TI  - Reversible Cerebral Vasoconstriction Syndrome: an important cause of thunderclap
      headache.
AB  - Reversible cerebral vasoconstriction syndrome (rCVS) is an important cause of
      acute severe headache that is poorly understood and under-recognised. It
      typically presents with recurrent thunderclap headaches and is characterised by
      multifocal, segmental constriction and dilatation of the cerebral arteries, shown
      by a 'string of beads' appearance, on cerebral angiography. We describe a case of
      rCVS in a 39-year-old male presenting with post-coital thunderclap headaches
      following a whiplash-type injury. 

PMID- 24940572
TI  - Can someone call my PA?
AB  - The aim of this paper is to outline the background of the Physician Associate
      (known in the USA as physician assistant1) role in the USA and follow its recent
      journey to the UK where it is becoming a rapidly developing new healthcare role.
      Through the use of two case studies from UK Hospital Trusts who are currently
      utilising Physician Associates (PAs) in their workforce we describe the
      implementation and development opportunities for the role, with particular
      reference to their role in Acute Medicine teams of the future. 

PMID- 24940573
TI  - Problem based review: the patient presenting with hyponatraemia.
AB  - Hyponatraemia is the most common electrolyte anomaly and is associated with
      significant morbidity and mortality. Patients with severe hyponatraemia often
      present to acute medical units with non-specific symptoms which can progress to
      overt neurological manifestations. There are many causes of hyponatriaemia, the
      most common being drug-induced causes, particularly thiazide diuretics, and the
      Syndrome of Inappropriate ADH Secretion (SIADH). Initial assessment should
      include a careful evaluation of the patient's volume status, which helps to
      identify the most likely cause. This article utilises a recent case which
      presented to our AMU to illustrate the importance of a careful and systematic
      assessment of patients presenting to hospital with hyponatraemia. The new
      vasopressin receptor antagonists are explored as an option for the management of
      severe hyponatraemia. 

PMID- 24940574
TI  - The young patient with acute bloody diarrhoea.
AB  - Acute bloody diarrhoea may be commonly encountered in the acute medical unit.
      Among young patients, the main differential diagnoses are acute infectious
      colitis, and first presentation of inflammatory bowel disease (IBD). A
      combination of clinical, laboratory, radiological, endoscopic and histological
      investigations are required to make the diagnosis. If inflammatory bowel disease
      is suspected, then the patient should be admitted to a specialist
      gastroenterology ward and receive input from the surgical team, IBD nurses and
      specialist stoma nurses. Intravenous steroid therapy for acute severe disease
      should be started before stool cultures are back unless there is a strong
      clinical suspicion of amoebiasis. All patients require thromboprophylaxis and
      close attention paid to fluid balance and nutritional requirements. Daily
      clinical review is required. The Travis criteria may be employed at day 3 to
      assess the likelihood of requiring surgery and plans for rescue therapy, medical
      or surgical should be made between day 3-7 if the patient is not responding
      adequately to initial medical therapy. 

PMID- 24940576
TI  - Indirect determination of dissolved silicate in surface water using energy
      dispersive X-ray fluorescence spectrometry.
AB  - An ultrasound-assisted methodology for the determination of dissolved silicate in
      water has been developed by combining the miniaturized ion-associated based
      preconcentration method with energy dispersive X-ray fluorescence spectrometry
      (EDXRF). The method has been devised for the determination of silicate through
      molybdenum in the ion-associated complex between 12-molybdosilicate and crystal
      violet. Because silicate is determined indirectly via molybdenum fluorescent
      radiation the difficulties resulting from low fluorescence yield and low energy
      of silicon radiation were successfully overcome. A good ratio of silicon to
      molybdenum (1 to 41) and a sensitive Kalpha line of molybdenum make possible the
      determination of low concentration of silicon in the form of dissolved silicate.
      Under optimized conditions, good linearity, up to 5 MUg of silicon in the form of
      silicate (r = 0.9990) and a detection limit of 9 ng mL(-1) were achieved. The
      total RSD for the EDXRF determination of silicate, followed by precipitation of
      the ion-associated complex and its dissolution in a microdrop of isoamyl alcohol,
      was 6.5%. The enrichment factor was equal to 142. The developed method was used
      to determine the dissolved silica content in surface waters. The accuracy and
      repeatability of the proposed procedure were checked by the standard addition
      method and compared to the results obtained using the ICP-OES technique. The
      recovery (in the 93-97% range) was satisfactory and indicated the usefulness of
      the developed procedure. 

PMID- 24940577
TI  - A single-molecule force-spectroscopic study on stabilization of G-quadruplex DNA
      by a telomerase inhibitor.
AB  - Single-molecule force spectroscopy was carried out using AFM force measurements
      for the purpose of direct observation of the stabilization of G-quadruplex DNA by
      a telomerase inhibitor, which is 5,10,15,20-tetrakis(N-methylpyridinium-4
      yl)porphyrin tetrakis(p-toluenesulfonate) (TMPyP). In AFM force measurements, we
      used an AFM tip and an Au substrate modified chemically with terminal
      biotinylated telomere DNA and streptavidin, respectively. The telomere DNA was
      fully stretched by the AFM tip based on the bridge formation between the AFM tip
      and the Au substrate through the streptavidin-biotin interaction. The force
      extension curves, which reflected the stretching of a single DNA molecule, were
      distinguished from all of the curves, judging from the rupture force and the
      contour length. The selected curves were analyzed using a worm-like chain model,
      and one of the fitting parameters, persistence length (lp), was used as an index
      for the stabilization of the G-quadruplex structure. Consequently, the lp value
      was significantly increased by the addition of TMPyP under the experimental
      conditions where the G-quadruplex structure could be formed. On the other hand,
      the value was hardly changed by the addition of TMPyP under the conditions except
      the above. Furthermore, the methodology developed and demonstrated in this work
      was applied to evaluate the stabilization of G-quadruplex DNA by other telomerase
      inhibitors such as ethidium bromide and p-xylene-bis(N-pyridinium bromide). 

PMID- 24940578
TI  - Electrochemiluminescence immunosensor using poly(l-histidine)-protected glucose
      dehydrogenase on Pt/Au bimetallic nanoparticles to generate an in situ co
      reactant.
AB  - In this work, Pt/Au bimetallic nanoparticles (Pt/Au NPs) were used as
      nanocarriers to develop an electrochemiluminescence (ECL) immunosensor for
      sensitive cardiac troponin I (cTnI) detection, coupling with enzyme-based signal
      amplification. First, gold nanoparticles modified Ru(phen)3(2+)-doped silica
      nanoparticles (Au@RuSiO2 NPs) with numerous luminophores were used as a platform,
      potentially increasing the signal intensity. Second, Pt/Au NPs with large surface
      area and rich surface atoms were a superior matrix for the immobilization of
      numerous antibodies (Ab2), poly(l-histidine) (PLH) and glucose dehydrogenase
      (GDH). More importantly, the PLH-protected GDH exhibited excellent enzymatic
      activity for the oxidation of glucose accompanied by the reduction of NAD(+) to
      NADH. The in situ generated NADH acted as a co-reactant of Ru(phen)3(2+),
      significantly enhancing the ECL signal. In this manner, the designed immunosensor
      displayed high sensitivity for the detection of cTnI in the range of 0.010 ng mL(
      1) to 10 ng mL(-1) with a detection limit of 3.3 pg mL(-1) (S/N = 3). The
      proposed strategy holds a new promise for highly sensitive bioassays for
      application in clinical analyses. 

PMID- 24940579
TI  - Zero net-flow in capillary electrophoresis using acrylamide based hydrogel.
AB  - Zero net-flow was observed when acrylamide based hydrogel was used in a vial at
      one end of a fused-silica capillary during electrophoresis with electroosmotic
      flow. We demonstrate the detection of anionic compounds with the anode at the
      detector end and the field-enhanced sample injection of anionic small molecule
      drugs in counter-electroosmotic flow capillary zone electrophoresis. 

PMID- 24940580
TI  - A fluorescent light-up probe with AIE characteristics for specific mitochondrial
      imaging to identify differentiating brown adipose cells.
AB  - We report the design and synthesis of a specific mitochondrial fluorescent probe
      AIE-MitoGreen-1 with AIE characteristics to monitor the mitochondrial morphology
      changes and identify the differentiation process of living brown adipose cells.
      The probe AIE-MitoGreen-1 has significant advantages such as high
      cellpermeability, good mitochondrial retention, low background fluorescence,
      large Stokes shift, and low toxicity.

PMID- 24940581
TI  - Reply to Gelman, Gaudart, Pericchi: More reasons to revise standards for
      statistical evidence.

PMID- 24940582
TI  - Reply to van Hoorn: Pitfalls of narrow interpretations of significance.

PMID- 24940583
TI  - The rising proportion of repeat teenage pregnancies in young  women presenting
      for termination of pregnancy from 1991 to 2007.

PMID- 24940584
TI  - Preface. Pseudogenes.

PMID- 24940585
TI  - MVA85A TB vaccine tested in newborns of HIV-positive mothers.

PMID- 24940586
TI  - GSK partners with Vodafone to increase childhood vaccinatin in  Mozambique.

PMID- 24940587
TI  - Reprocessing unsatisfactory ThinPrep papanicolaou tests using a modified SurePath
      preparation technique.
AB  - BACKGROUND: The frequency of unsatisfactory gynecologic specimens has increased
      in the study laboratory over the last few years due to the advent of personal
      lubricants. Similarly, lysed blood, protein, and necrotic debris present a
      challenge in terms of negative cell transference caused by a clogged filter. In
      the current study, the authors evaluated the potential use of a modified SurePath
      reprocessing technique to decrease the frequency of unsatisfactory specimens.
      METHODS: An aliquot for human papillomavirus testing was set aside and the
      remaining specimen in the ThinPrep vial was submitted for sedimentation. A
      methanol wash was performed using preservative that was added to the remaining
      sediment. The specimen was vortexed and a protein wash of Tris-buffered deionized
      water was added before processing. The specimens were stained using the ThinPrep
      staining protocol. Both the original specimen and the reprocessed specimens were
      manually reviewed by 1 cytotechnologist and 2 pathologists to determine specimen
      adequacy. RESULTS: A total of 1937 ThinPrep Papanicolaou tests were reprocessed
      and examined. Of these, 1093 (56%) specimens were satisfactory, 624 of which
      (57%) demonstrated evidence of a transformation zone component. Epithelial cell
      abnormalities were identified in 116 specimens (10.6%), including 11 high-grade
      squamous intraepithelial lesion specimens (1.0%); 5 specimens with a
      classification of atypical squamous cells, cannot rule out a high-grade lesion
      (0.5%); 21 low-grade squamous intraepithelial lesion specimens (1.9%); and 79
      specimens classified as atypical squamous cells of undetermined significance
      (7.2%). CONCLUSIONS: The modified SurePath processing technique was adept at
      handling nearly all of the challenges that biological and environmental
      conditions (blood, protein, lubricant, etc) present in liquid-based filter
      preparations. A total of 1093 (56%) of 1937 unsatisfactory ThinPrep Papanicolaou
      tests were converted to a satisfactory state, resulting in 116 abnormalities
      (10.6%) being diagnosed that otherwise would have gone undetected

PMID- 24940588
TI  - Robin Holliday (1932-2014).

PMID- 24940589
TI  - [Lyme disease].

PMID- 24940591
TI  - The white coats are coming. S.C. med school requires students to become EMTs.

PMID- 24940590
TI  - Chemical burn care: a review of best practices.

PMID- 24940592
TI  - When veterans become victims. Special training prepares Phoenix providers to deal
      with the unique needs of returning military.

PMID- 24940593
TI  - Video verite: What does recording cardiac resuscitations show? There may be
      benefit, but there are some hurdles to overcome too.

PMID- 24940594
TI  - A novel square-planar Ni(II) complex with an amino-carboxamido-dithiolato-type
      ligand as an active-site model of NiSOD.
AB  - To understand the role of the unique equatorial coordination environment at the
      active center in nickel superoxide dismutase (NiSOD), we prepared a novel Ni(II)
      complex with an amino-carboxamido-dithiolato-type square-planar ligand (1,
      [Ni(2+)(L1)](-)) as a model of the NiSOD active site. Complex 1 has a low-spin
      square-planar structure in all solvents. Interestingly, the absorption wavelength
      and nu(C?O) stretching vibrations of 1 are affected by solvents. This provides an
      indication that the carbonyl oxygens participate in hydrogen-bonding interactions
      with solvents. These interactions are reflected in the redox potentials; the peak
      potential of an anodic wave (Epa) values of Ni(II)/Ni(III) waves for 1 are
      shifted to a positive region for solvents with higher acceptor numbers. This
      indicates that the disproportionation of superoxide anion by NiSOD may be
      regulated by hydrogen-bonding interactions between the carboxamido carbonyl and
      electrophilic molecules through fine-tuning of the redox potential for optimal
      SOD activity. Interestingly, the Epa value of the Ni(III)/Ni(II) couple in 1 in
      water (+0.303 V vs normal hydrogen electrode (NHE)) is similar to that of NiSOD
      (+0.290 V vs NHE). We also investigated the superoxide-reducing and -oxidizing
      reactions of 1. First, 1 reacts with superoxide to yield the superoxide-bound
      Ni(II) species (UV-vis: 425, 525, and ~650 nm; electron paramagnetic resonance
      (EPR) (4 K): g// = 2.21, g? = 2.01; resonance Raman: nu((16)O-(16)O)/nu((18)O
      (18)O) = 1020/986 cm(-1)), which is then oxidized to Ni(III) state only in the
      presence of both a proton and 1-methylimidazole, as evidenced by EPR spectra.
      Second, EPR spectra indicate that the oxidized complex of 1 with 1
      methylimidazole at the axial site can be reduced by reaction with superoxide. The
      Ni(III) complex with 1-methylimidazole at the axial site does not participate in
      any direct interaction with azide anion (pKa 4.65) added as mimic of superoxide
      (pKa 4.88). According to these data, we propose the superoxide disproportionation
      mechanism in superoxide-reducing and -oxidizing steps of NiSOD in both Ni(II) and
      Ni(III) states. 

PMID- 24940595
TI  - New plant-parasitic nematode from the mostly mycophagous genus Bursaphelenchus
      discovered inside figs in Japan.
AB  - A new nematode species, Bursaphelenchus sycophilus n. sp. is described. The
      species was found in syconia of a fig species, Ficus variegata during a field
      survey of fig-associated nematodes in Japan. Because it has a well-developed
      stylet and pharyngeal glands, the species is considered an obligate plant
      parasite, and is easily distinguished from all other fungal-feeding species in
      the genus based upon these characters. Although B. sycophilus n. sp. shares an
      important typological character, male spicule possessing a strongly recurved
      condylus, with the "B. eremus group" and the "B. leoni group" of the genus, it
      was inferred to be monophyletic with the "B. fungivorus group". The uniquely
      shaped stylet and well-developed pharyngeal glands is reminiscent of the fig
      floret parasitic but paraphyletic assemblage of "Schistonchus". Thus, these
      morphological characters appear to be an extreme example of convergent evolution
      in the nematode family, Aphelenchoididae, inside figs. Other characters shared by
      the new species and its close relatives, i.e., lack of ventral P1 male genital
      papilla, female vulval flap, and papilla-shaped P4 genital papillae in males,
      corroborate the molecular phylogenetic inference. The unique biological character
      of obligate plant parasitism and highly derived appearance of the ingestive
      organs of Bursaphelenchus sycophilus n. sp. expands our knowledge of the
      potential morphological, physiological and developmental plasticity of the genus
      Bursaphelenchus. 

PMID- 24940597
TI  - Persistence of contrasting traditions in cultural evolution: unpredictable
      payoffs generate slower rates of cultural change.
AB  - We report an experimental test of the hypothesis that contrasting traditions will
      persist for longer, maintaining cultural differences between otherwise similar
      groups, under conditions of uncertainty about payoffs from individual learning.
      We studied the persistence of two alternative, experimentally-introduced, task
      solutions in chains of human participants. In some chains, participants were led
      to believe that final payoffs would be difficult to predict for an innovative
      solution, and in others, participants were aware that their final payoff would be
      directly linked to their immediate solution. Although the difference between the
      conditions was illusory (only participants' impressions were manipulated, not
      actual payoffs) clear differences were found between the conditions. Consistent
      with predictions, in the chains that were less certain about final payoffs, the
      distinctive variants endured over several replacement "generations" of
      participants. In contrast, in the other chains, the influence of the
      experimentally-introduced solutions was rapidly diluted by participants'
      exploration of alternative approaches. The finding provides support for the
      notion that rates of cultural change are likely to be slower for behaviors for
      which the relationship between performance and payoff may be hard to predict. 

PMID- 24940596
TI  - Toxoplasma gondii decreases the reproductive fitness in mice.
AB  - Toxoplasma gondii is a common protozoan parasite that infects warm-blooded
      animals throughout the world, including mice and humans. During infection, both,
      the parasite and the host, utilize various mechanisms to maximize their own
      reproductive success. Mice and humans are both the intermediate hosts for
      Toxoplasma gondii, which forms specialized vacuoles containing reproductive cysts
      in the formers' tissue. As half of the human population is infected, developing a
      disease called toxoplasmosis, along with an ever-growing number of couples
      suffering with idiopathic infertility, it is therefore surprising that there is a
      lack of research on how Toxoplasma gondii can alter reproductive parameters. In
      this study, a detailed histometric screening of the testicular function along
      with the levels of the pituitary luteinizing hormone (LH) were analysed in
      infected mice. Data on relative testis and epididymis weight, and sperm count
      were also collected. Based on the results obtained, the level of LH in the urine
      of Toxoplasma gondii infected mice was lower compared to the control. In direct
      correlation with the hormone level, testicular function and sperm production was
      also significantly lower in Toxoplasma gondii positive group using sperm count
      and histometric analysis as a marker. Not only were the number of leptotene
      primary spermatocytes and spermatids lowered, but the number of Sertoli cells and
      the tubule diameter were elevated. In parallel, a pilot epigenetic study on
      global testicular methylation, and specific methylation of Crem, Creb1 and
      Hspa1genes essential for successfully ongoing spermatogenesis was performed.
      Global methylation was elevated in Toxoplasma infected mice, and differences in
      the DNA methylation of selected genes were detected between the Toxoplasma
      positive and control group. These findings demonstrate a direct relation between
      Toxoplasma gondii infection and the decrease of male reproductive fitness in
      mice, which may contribute to an increase of idiopathic infertility in humans. 

PMID- 24940598
TI  - Migrations of green turtles (Chelonia mydas) between nesting and foraging grounds
      across the Coral Sea.
AB  - Marine megafauna tend to migrate vast distances, often crossing national borders
      and pose a significant challenge to managers. This challenge is particularly
      acute in the Pacific, which contains numerous small island nations and thousands
      of kilometers of continental margins. The green sea turtle, Chelonia mydas, is
      one such megafauna that is endangered in Pacific waters due to the
      overexploitation of eggs and adults for human consumption. Data from long-term
      tagging programs in Queensland (Australia) and New Caledonia were analysed to
      investigate the migrations by C. mydas across the Coral Sea between their nesting
      site and their feeding grounds. A review of data collected over the last 50 years
      by different projects identified multiple migrations of C. mydas to and from New
      Caledonia (n = 97) and indicate that turtles foraging in New Caledonia nest in
      the Great Barrier Reef (Australia) and vice versa. Several explanations exist for
      turtles exhibiting this energetically costly movement pattern from breeding to
      distant foraging grounds (1200-2680 km away) despite viable foraging habitat
      being available in the local vicinity. These include hatchling drift, oceanic
      movements and food abundance predictability. Most of the tag recoveries in New
      Caledonia belonged to females from the south Great Barrier Reef genetic stock.
      Some females (n = 2) even showed fidelity to foraging sites located 1200 km away
      from the nesting site located in New Caledonia. This study also reveals
      previously unknown migrations pathways of turtles within the Coral Sea.

PMID- 24940599
TI  - Plasma metabolomic profiling to reveal antipyretic mechanism of Shuang-huang-lian
      injection on yeast-induced pyrexia rats.
AB  - Shuang-huang-lian injection (SHLI) is a famous Chinese patent medicine, which has
      been wildly used in clinic for the treatment of acute respiratory tract
      infection, pneumonia, influenza, etc. The existing randomized controlled trial
      (RCT) studies suggested that SHLI could afford a certain anti-febrile action.
      However, seldom does research concern the pharmacological mechanisms of SHLI. In
      the current study, we explored plasma metabolomic profiling technique and
      selected potential metabolic markers to reveal the antipyretic mechanism of SHLI
      on yeast-induced pyrexia rat model using UPLC-Q-TOF/MS coupled with multivariate
      statistical analysis and pattern recognition techniques. We discovered a
      significant perturbance of metabolic profile in the plasma of fever rats and
      obvious reversion in SHLI-administered rats. Eight potential biomarkers, i.e. 1)
      3-hydeoxybutyric acid, 2) leucine, 3) 16:0 LPC, 4) allocholic acid, 5) vitamin
      B2, 6) Cys-Lys-His, 7) 18:2 LPC, and 8) 3-hydroxychola-7, 22-dien-24-oic acid,
      were screened out by OPLS-DA approach. Five potential perturbed metabolic
      pathways, i.e. 1) valine, leucine, and isoleucine biosynthesis, 2)
      glycerophospholipid metabolism, 3) ketone bodies synthesis and degradation, 4)
      bile acid biosynthesis, and 5) riboflavin metabolism, were revealed to relate to
      the antipyretic mechanisms of SHLI. Overall, we investigated antipyretic
      mechanisms of SHLI at metabolomic level for the first time, and the obtained
      results highlights the necessity of adopting metabolomics as a reliable tool for
      understanding the holism and synergism of Chinese patent drug.

PMID- 24940605
TI  - Decontamination efficacy of three commercial-off-the-shelf (COTS) sporicidal
      disinfectants on medium-sized panels contaminated with surrogate spores of
      Bacillus anthracis.
AB  - In the event of a wide area release and contamination of a biological agent in an
      outdoor environment and to building exteriors, decontamination is likely to
      consume the Nation's remediation capacity, requiring years to cleanup, and
      leading to incalculable economic losses. This is in part due to scant body of
      efficacy data on surface areas larger than those studied in a typical laboratory
      (5*10-cm), resulting in low confidence for operational considerations in sampling
      and quantitative measurements of prospective technologies recruited in effective
      cleanup and restoration response. In addition to well-documented fumigation-based
      cleanup efforts, agencies responsible for mitigation of contaminated sites are
      exploring alternative methods for decontamination including combinations of
      disposal of contaminated items, source reduction by vacuuming, mechanical
      scrubbing, and low-technology alternatives such as pH-adjusted bleach pressure
      wash. If proven effective, a pressure wash-based removal of Bacillus anthracis
      spores from building surfaces with readily available equipment will significantly
      increase the readiness of Federal agencies to meet the daunting challenge of
      restoration and cleanup effort following a wide-area biological release. In this
      inter-agency study, the efficacy of commercial-of-the-shelf sporicidal
      disinfectants applied using backpack sprayers was evaluated in decontamination of
      spores on the surfaces of medium-sized (~1.2 m2) panels of steel, pressure
      treated (PT) lumber, and brick veneer. Of the three disinfectants, pH-amended
      bleach, Peridox, and CASCAD evaluated; CASCAD was found to be the most effective
      in decontamination of spores from all three panel surface types. 

PMID- 24940603
TI  - New Clox Systems for rapid and efficient gene disruption in Candida albicans.
AB  - Precise genome modification is essential for the molecular dissection of Candida
      albicans, and is yielding invaluable information about the roles of specific gene
      functions in this major fungal pathogen of humans. C. albicans is naturally
      diploid, unable to undergo meiosis, and utilizes a non-canonical genetic code.
      Hence, specialized tools have had to be developed for gene disruption in C.
      albicans that permit the deletion of both target alleles, and in some cases, the
      recycling of the Candida-specific selectable markers. Previously, we developed a
      tool based on the Cre recombinase, which recycles markers in C. albicans with 90
      100% efficiency via site-specific recombination between loxP sites. Ironically,
      the utility of this system was hampered by the extreme efficiency of Cre, which
      prevented the construction in Escherichia coli of stable disruption cassettes
      carrying a methionine-regulatable CaMET3p-cre gene flanked by loxP sites.
      Therefore, we have significantly enhanced this system by engineering new Clox
      cassettes that carry a synthetic, intron-containing cre gene. The Clox kit
      facilitates efficient transformation and marker recycling, thereby simplifying
      and accelerating the process of gene disruption in C. albicans. Indeed,
      homozygous mutants can be generated and their markers resolved within two weeks.
      The Clox kit facilitates strategies involving single marker recycling or multi
      marker gene disruption. Furthermore, it includes the dominant NAT1 marker, as
      well as URA3, HIS1 and ARG4 cassettes, thereby permitting the manipulation of
      clinical isolates as well as genetically marked strains of C. albicans. The
      accelerated gene disruption strategies afforded by this new Clox system are
      likely to have a profound impact on the speed with which C. albicans pathobiology
      can be dissected. 

PMID- 24940604
TI  - A nationwide survey of mild cognitive impairment and dementia, including very
      mild dementia, in Taiwan.
AB  - An increasing population of dementia patients produces substantial societal
      impacts. We assessed the prevalence of mild cognitive impairment (MCI) and all
      cause dementia, including very mild dementia (VMD), in Taiwan. In a nationwide
      population-based cross-sectional survey, participants were selected by
      computerized random sampling from all 19 Taiwan counties and were enrolled
      between December 2011 and March 2013. Cases were identified through in-person
      interviews based on the National Institute on Aging-Alzheimer's Association
      clinical criteria. Demographic data and histories involving mental status and
      function in daily living were collected. The principal objective assessments were
      the Taiwanese Mental Status Examination and Clinical Dementia Rating. In all,
      10,432 people aged 65 years or older (mean age 76.2 +/- 6.7, 52.3% women) were
      interviewed. The age-adjusted prevalence of all-cause dementia was 8.04% (95% CI
      7.47-8.61), including a 3.25% (95% CI 2.89-3.61) prevalence of VMD; that of MCI
      was 18.76% (95% CI 17.91-19.61). Women had a higher prevalence than men of both
      all-cause dementia (9.71% vs. 6.36%) and MCI (21.63% vs. 15.57%). MCI affects a
      considerable portion of the population aged 65 and above in Taiwan. The inclusion
      of VMD yields dementia prevalence rates higher than those previously reported
      from Taiwan. Old age, female gender, and a low educational level are significant
      associated factors.

PMID- 24940607
TI  - Enhancement in ion adsorption rate and desalination efficiency in a capacitive
      deionization cell through improved electric field distribution using electrodes
      composed of activated carbon cloth coated with zinc oxide nanorods.
AB  - Electrodes composed of activated carbon cloth (ACC) coated with zinc oxide (ZnO)
      nanorods are compared with plain ACC electrodes, with respect to their
      desalination efficiency of a 17 mM NaCl solution at different applied potentials.
      Polarization of the ZnO nanorods increased the penetration depth and strength of
      the electric field between the electrodes, leading to an increase in the
      capacitance and charge efficiency at reduced input charge ratios. Uniform
      distribution of the electric field lines between two electrodes coated with ZnO
      nanorods led to faster ion adsorption rates, reduced the electrode saturation
      time, and increased the average desalination efficiency by ~45% for all applied
      potentials. The electrodes were characterized for active surface area,
      capacitance from cyclic voltammetry, theoretical assessment of surface area
      utilization, and the magnitude of electric field force acting on an ion of unit
      charge for each potential. 

PMID- 24940606
TI  - miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical
      outcome in non-KRAS mutant patients treated with 3rd line cetuximab and
      irinotecan.
AB  - INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular
      processes and have shown promising potential as prognostic markers for disease
      outcome in patients with cancer. The aim of the present study was to find miRNA
      expression profiles in whole blood that were prognostic for overall survival (OS)
      in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and
      irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with
      cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs
      were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0.
      Mutation status of KRAS, BRAF, and PI3KCA was known. RESULTS: After Bonferroni
      adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR
      324-3p), were found associated with short OS. miR-345 was the strongest
      prognostic miRNA, significant in the full cohort and in the non-KRAS mutant
      population. miR-345, as a continuous variable in the full cohort, resulted in a
      hazard ratio (HR) of 2.38 per IQR (CI 95%: 1.8-3.1, P-value = 2.86e-07,
      Bonferroni adjusted, univariable analysis) and a HR = 1.75 per IQR (CI 95%: 1.24
      2.48, P-Wald = 1.45e-03) in the multivariable analysis adjusted for gender, age,
      KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free
      survival (PFS) with a HR = 1.63 per IQR (CI 95%: 1.25-2.114, P-Wald = 2.92e-4) in
      the multivariable analysis. In addition, high miR-345 expression was associated
      with lack of response to treatment with cetuximab and irinotecan. CONCLUSION: We
      identified miR-345 in whole blood as a potential biomarker for clinical outcome.
      MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and
      also in the non-KRAS mutant population.

PMID- 24940608
TI  - Novel microstructured sildenafil dosage forms as wound healing promoters.
AB  - PURPOSE: Study the possible benefit of combining biodegradable polymers with
      sildenafil citrate (SC) in wound healing. METHOD: Biodegradable micronized
      powdered formulations of SC were prepared by spray drying using chitosan (P1) or
      chitosan/gum Arabic (P2). Powders were characterized by differential scanning
      calorimetry, Scanning electron microscope, particle size analysis, flow and
      swelling behavior. The powders were also incorporated into microstructured gels
      and in vitro SC release from powders and gels was tested. In vivo wound healing
      acceleration was tested by measuring area contraction of excision wounds and
      histologically. Post-healing tensile strength (TS) for incision wounds in rats
      receiving powder formulations was tested. RESULTS: The powders were in the micron
      size range showing no SC-polymers interaction. Powders had poor flow with angle
      of repose (theta) of 41 - 48 degrees , and high moisture uptake reaching 107% for
      placebo powder P1. Good excision wound healing was seen with P1 and G1
      formulations showing 98.4 and 98.5% reduction in wound area, respectively,
      compared with 83% for the control. Incision wounds were improved with P1 showing
      TS value of 6.9 compared with 3.7 kg/cm2 for control. Histological examinations
      supported. CONCLUSION: Spray-dried chitosan/SC powder (P1) and its gel form (G1)
      could be promising wound healing promoters as supported by the histological
      examinations.

PMID- 24940612
TI  - Transition-metal-catalyzed asymmetric allylic dearomatization reactions.
AB  - Dearomatization reactions serve as powerful methods for the synthesis of highly
      functionalized, three-dimensional structures starting with simple planar aromatic
      compounds. Among processes of this type, catalytic asymmetric dearomatization
      (CADA) reactions are attractive owing to the large number of aromatic compounds
      that are readily available and the fact that they enable direct access to
      enantiopure polycycles and spirocycles, which frequently are key structural
      motifs in biologically active natural products and pharmaceuticals. However, as a
      consequence of their high stabilities, arenes only difficultly participate in
      dearomatization reactions that take place with high levels of enantioselectivity.
      Transition-metal-catalyzed asymmetric allylic substitution reactions have been
      demonstrated to be powerful methods for enantioselective formation of C-C and C-X
      (X = O, N, S, etc.) bonds. However, the scope of these processes has been
      explored mainly using soft carbon nucleophiles, some hard carbon nucleophiles
      such as enolates and preformed organometallic reagents, and heteroatom
      nucleophiles. Readily accessible aromatic compounds have been only rarely used
      directly as nucleophiles in these reactions. In this Account, we present the
      results of studies we have conducted aimed at the development of transition-metal
      catalyzed asymmetric allylic dearomatization reactions. By utilizing this general
      process, we have devised methods for direct dearomatization of indoles, pyrroles,
      phenols, naphthols, pyridines, and pyrazines, which produce various highly
      functionalized structural motifs bearing all-carbon quaternary stereogenic
      centers in a straightforward manner. In mechanistic investigations of the
      dearomatization process, we found that the five-membered spiroindolenines serve
      as intermediates, which readily undergo stereospecific allylic migration to form
      corresponding tetrahydro-1H-carbazoles upon treatment with a catalytic amount of
      TsOH. It is worth noting that no notable loss of the enantiomeric excess of the
      spiroindolenine derivatives takes place during the rearrangement process as a
      consequence of the intervention of a "three-center-two-electron"-type transition
      state, a proposal that has gained support from the results of DFT calculations.
      Equally intriguing, upon tuning of the electronic nature of the tethers, pyrroles
      or indoles undergo unprecedented Ir or Ru catalyzed intramolecular allylic
      alkylation promoted dearomatization/migration reactions. The operation of this
      novel reaction pathway provides additional information leading to a greater
      mechanistic understanding of the transition-metal-catalyzed enantioselective
      intramolecular functionalizations of pyrroles and indoles. The combined results
      of this effort provide not only methods for the efficient synthesis of highly
      enantioenriched fused and spiro polycycles but also novel strategies in the field
      of asymmetric catalysis.

PMID- 24940609
TI  - Beat-to-beat cycle length variability of spontaneously beating guinea pig
      sinoatrial cells: relative contributions of the membrane and calcium clocks.
AB  - The heartbeat arises rhythmically in the sino-atrial node (SAN) and then spreads
      regularly throughout the heart. The molecular mechanism underlying SAN rhythm has
      been attributed by recent studies to the interplay between two clocks, one
      involving the hyperpolarization activated cation current If (the membrane clock),
      and the second attributable to activation of the electrogenic NaCa exchanger by
      spontaneous sarcoplasmic releases of calcium (the calcium clock). Both mechanisms
      contain, in principle, sources of beat-to-beat cycle length variability, which
      can determine the intrinsic variability of SAN firing and, in turn, contribute to
      the heart rate variability. In this work we have recorded long sequences of
      action potentials from patch clamped guinea pig SAN cells (SANCs) perfused, in
      turn, with normal Tyrode solution, with the If inhibitor ivabradine (3 uM), then
      back to normal Tyrode, and again with the ryanodine channels inhibitor ryanodine
      (3 uM). We have found that, together with the expected increase in beating cycle
      length (+25%), the application of ivabradine brought about a significant and
      dramatic increase in beat-to-beat cycle length variability (+50%). Despite the
      similar effect on firing rate, ryanodine did not modify significantly beat-to
      beat cycle length variability. Acetylcholine was also applied and led to a 131%
      increase of beating cycle length, with only a 70% increase in beat-to-beat cycle
      length variability. We conclude that the main source of inter-beat variability of
      SANCs firing rate is related to the mechanism of the calcium clock, whereas the
      membrane clock seems to act in stabilizing rate. Accordingly, when the membrane
      clock is silenced by application of ivabradine, stochastic variations of the
      calcium clock are free to make SANCs beating rhythm more variable. 

PMID- 24940611
TI  - Raman spectroscopy insights into the size-induced structural transformation in
      SnSe nanolayers.
AB  - Raman spectroscopy is used to probe the structural changes in [SnSe]m[MoSe2]n
      ferecrystal thin films as a function of m, the number of bilayers of SnSe. In
      spite of the interleaved structure in the intergrowths, Raman spectra can be
      described as a superposition of spectra from the individual components,
      indicating that the interaction at the interface between the components is
      relatively weak. Analysis of room-temperature Raman spectra indicate that the
      MoSe2 layers separating the SnSe layers are nanocrystalline in all of the samples
      studied, with little change as the number of Se-Mo-Se trilayers (n) or SnSe
      bilayers (m) increases, reflecting the rotational disorder between adjacent
      trilayers. A thickness-dependent, continuous transition occurs in the SnSe layer
      as m is increased, from a pseudotetragonal structure when the layers are thin to
      a bulk-like orthorhombic SnSe structure when the SnSe layer thickness is
      increased. Polarization analysis of the Raman scattering from these materials
      allows the symmetry evolution of the SnSe layers through this transition to be
      determined. 

PMID- 24940610
TI  - The Nutritional Value of Protein-hydrolyzed Formulae.
AB  - Allergy to cow's milk proteins is a challenging condition in early infancy.
      Allergic infants may be predisposed to impairments of growth from either the
      disease itself or the nutritional constraints of the exclusion diet they should
      follow. Formulae based on extensively hydrolyzed cow's milk proteins are widely
      used, representing therapy, and constituting 100% nutrient source in the first
      four to six months of life and half the daily nutrient intake in the second
      semester of life. In some cases, these products are used also for preventive
      purposes. Some impairments in growth have been reported for infants using these
      products, even if mostly limited to the first year of life, with no apparent
      consequences in either the medium or long term. The macronutrient content of
      infant formulae based on protein hydrolysates, whichever the source, should
      carefully be tested not only as far as the optimal utilization of nitrogenous
      sources but also on the nature and metabolic fate of non-nitrogen caloric
      sources, represented by carbohydrates and fats, and micronutrients, particularly
      iron. It is recommended that studies aimed at the allergologic effects of these
      products also include an appropriate nutritional evaluation to determine their
      efficiency.

PMID- 24940613
TI  - Progress on understanding atmospheric mercury hampered by uncertain measurements.

PMID- 24940614
TI  - Proteomic analysis of mouse testis reveals perfluorooctanoic acid-induced
      reproductive dysfunction via direct disturbance of testicular steroidogenic
      machinery.
AB  - Perfluorooctanoic acid (PFOA) is a ubiquitous environmental pollutant suspected
      of being an endocrine disruptor; however, mechanisms of male reproductive
      disorders induced by PFOA are poorly understood. In this study, male mice were
      exposed to 0, 0.31, 1.25, 5, and 20 mg PFOA/kg/day by oral gavage for 28 days.
      PFOA significantly damaged the seminiferous tubules and reduced testosterone and
      progesterone levels in the testis in a dose-dependent manner. Furthermore, PFOA
      exposure reduced sperm quality. We identified 93 differentially expressed
      proteins between the control and the 5 mg/kg/d PFOA treated mice using a
      quantitative proteomic approach. Among them, insulin like-factor 3 (INSL3) and
      cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A1) as Leydig-cell
      specific markers were significantly decreased. We examined in detail the
      expression patterns of CYP11A1 and associated genes involved in steroidogenesis
      in the mouse testis. PFOA inhibited the mRNA and protein levels of CYP11A1 and
      the mRNA levels of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in a dose
      dependent manner. Moreover, in vitro study showed the reduction in progesterone
      levels was accompanied by decreased expression of CYP11A1 in cAMP-stimulated mLTC
      1 cells. Our findings indicate that PFOA exposure can impair male reproductive
      function, possibly by disturbing testosterone levels, and CPY11A1 may be a major
      steroidogenic enzyme targeted by PFOA. 

PMID- 24940616
TI  - Copper(II) anilides in sp3 C-H amination.
AB  - We report a series of novel beta-diketiminato copper(II) anilides [Cl2NN]Cu-NHAr
      that participate in C-H amination. Reaction of H2NAr (Ar = 2,4,6-Cl3C6H2
      (Ar(Cl3)), 3,5-(CF3)2C6H3 (Ar(F6)), or 2-py) with the copper(II) t-butoxide
      complex [Cl2NN]Cu-(t)OBu yields the corresponding copper(II) anilides [Cl2NN]Cu
      NHAr. X-ray diffraction of these species reveal three different bonding modes for
      the anilido moiety: kappa(1)-N in the trigonal [Cl2NN]Cu-NHAr(Cl3) to dinuclear
      bridging in {[Cl2NN]Cu}2(MU-NHAr(F6))2 and kappa(2)-N,N in the square planar
      [Cl2NN]Cu(kappa(2)-NH-2-py). Magnetic data reveal a weak antiferromagnetic
      interaction through a pi-stacking arrangement of [Cl2NN]Cu-NHAr(Cl3); solution
      EPR data are consistent with monomeric species. Reaction of [Cl2NN]Cu-NHAr with
      hydrocarbons R-H (R-H = ethylbenzene and cyclohexane) reveals inefficient
      stoichiometric C-H amination with these copper(II) anilides. More rapid C-H
      amination takes place, however, when (t)BuOO(t)Bu is used, which allows for HAA
      of R-H to occur from the (t)BuO(*) radical generated by reaction of [Cl2NN]Cu and
      (t)BuOO(t)Bu. The principal role of these copper(II) anilides [Cl2NN]Cu-NHAr is
      to capture the radical R(*) generated from HAA by (t)BuO(*) to give
      functionalized aniline R-NHAr, resulting in a novel amino variant of the Kharasch
      Sosnovsky reaction. 

PMID- 24940615
TI  - Is CD133 expression a prognostic biomarker of non-small-cell lung cancer? A
      systematic review and meta-analysis.
AB  - BACKGROUND: The clinical and prognostic significance of CD133 in non-small-cell
      lung cancer (NSCLC) remains controversial. To clarify a precise determinant of
      the clinical significance of CD133, we conducted a systematic review and meta
      analysis to evaluate the association of CD133 with prognosis and
      clinicopathological features of NSCLC patients. METHODS: The electronic and
      manual searches were performed through the database of Pubmed, Medline, Web of
      Science, Scopus, and Chinese CNKI (from January 1, 1982 to January 1, 2014) for
      titles and abstracts by using the following keywords: "CD133", "ac133" or
      "Prominin-1", and "lung cancer" to identify the studies eligible for our
      analysis. Meta-analysis was performed by using Review Manager 5.0 and the
      outcomes included the overall survival and various clinicopathological features.
      RESULTS: A total of 23 studies were finally included, and our results showed that
      CD133 level was significantly correlated with the overall survival (OR = 2.25,
      95% CI: 1.24-4.07, P = 0.008) of NSCLC patients but not with the disease free
      survival (OR = 1.33, 95% CI = 0.77-2.30, P = 0.31). With respect to
      clinicopathological features, CD133 level was positively correlated with lymph
      node metastasis (OR = 1.99, 95%CI = 1.06-3.74, P = 0.03), but not correlated with
      the histological classification (OR = 1.00, 95%CI = 0.81-1.23, P = 0.99(ac), OR =
      0.87, 95%CI = 0.61-1.24, P = 0.45(sc)), or differentiation (OR = 0.94, 95%CI 0.53
      1.68, Z = 0.20, P = 0.84 random-effect) of NSCLC patients. CONCLUSION: High level
      of CD133 expression trends to correlate with a worse prognosis and a higher rate
      of lymph node metastasis in NSCLC patients, revealing CD133 as a potential
      pathological prognostic marker for NSCLC patients.

PMID- 24940618
TI  - Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model
      in vivo.
AB  - OBJECTIVE: In clinical trials, retinitis pigmentosa patients implanted with a
      retinal prosthetic device show enhanced spatial vision, including the ability to
      read large text and navigate. New prosthetics aim to increase spatial resolution
      by decreasing pixel/electrode size and limiting current spread. To examine
      spatial resolution of a new prosthetic design, we characterized and compared two
      photovoltaic array (PVA) designs and their interaction with the retina after
      subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3).
      APPROACH: PVAs were implanted subretinally at two stages of degeneration and
      assessed in vivo using extracellular recordings in the superior colliculus (SC).
      Several aspects of this interaction were evaluated by varying duration,
      irradiance and position of a near infrared laser focused on the PVA. These
      characteristics included: activation threshold, response linearity, SC signal
      topography and spatial localization. The major design difference between the two
      PVA designs is the inclusion of local current returns in the newer design. MAIN
      RESULTS: When tested in vivo, PVA-evoked response thresholds were independent of
      pixel/electrode size, but differ between the new and old PVA designs. Response
      thresholds were independent of implantation age and duration (?7.5 months). For
      both prosthesis designs, threshold intensities were within established safety
      limits. PVA-evoked responses require inner retina synaptic transmission and do
      not directly activate retinal ganglion cells. The new PVA design evokes local
      retinal activation, which is not found with the older PVA design that lacks local
      current returns. SIGNIFICANCE: Our study provides in vivo evidence that
      prosthetics make functional contacts with the inner nuclear layer at several
      stages of degeneration. The new PVA design enhances local activation within the
      retina and SC. Together these results predict that the new design can potentially
      harness the inherent processing within the retina and is likely to produce higher
      spatial resolution in patients.

PMID- 24940619
TI  - Heterogeneous EGFR gene copy number increase is common in colorectal cancer and
      defines response to anti-EGFR therapy.
AB  - Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although
      only a subset of patients benefit from the treatment. While KRAS mutation
      predicts non-responsiveness, positive predictive markers are not in clinical
      practice. We previously showed that immunohistochemistry (IHC)-guided EGFR gene
      copy number (GCN) analysis may identify CRC patients benefiting from anti-EGFR
      treatment. Here we tested the predictive value of such analysis in
      chemorefractory metastatic CRC, elucidated EGFR GCN heterogeneity within the
      tumors, and evaluated the association between EGFR GCN, KRAS status, and anti
      EGFR antibody response in CRC cell lines. The chemorefractory patient cohort
      consisted of 54 KRAS wild-type (WT) metastatic CRC patients. EGFR GCN status was
      analyzed by silver in situ hybridization using a cut-off value of 4.0 EGFR gene
      copies/cell. KRAS-WT and KRAS mutant CRC cell lines with different EGFR GCN were
      used in in vitro studies. The chemorefractory CRC tumors with EGFR GCN increase
      (>=4.0) responded better to anti-EGFR therapy than EGFR GCN (<4.0) tumors
      (clinical benefit, P = 0.0004; PFS, HR = 0.23, 95% CI 0.12-0.46). EGFR GCN
      counted using EGFR IHC guidance was significantly higher than the value from
      randomly selected areas verifying intratumoral EGFR GCN heterogeneity. In CRC
      cell lines, EGFR GCN correlated with EGFR expression. Best anti-EGFR response was
      seen with KRAS-WT, EGFR GCN = 4 cells and poorest response with KRAS-WT, EGFR GCN
      = 2 cells. Anti-EGFR response was associated with AKT and ERK1/2 phosphorylation,
      which was effectively inhibited only in cells with KRAS-WT and increased EGFR
      GCN. In conclusion, IHC-guided EGFR GCN is a promising predictor of anti-EGFR
      treatment efficacy in chemorefractory CRC. 

PMID- 24940620
TI  - Osteoblast-secreted factors promote proliferation and osteogenic differentiation
      of bone marrow stromal cells via VEGF/heme-oxygenase-1 pathway.
AB  - The hypoxia-inducible factors (HIFalpha) are the critical factors that couple
      angiogenesis and osteogenesis by activating transcription of VEGF in osteoblasts.
      Mice lacking von Hippel-Lindau gene (Vhl), thus overexpressing HIFalpha in
      osteoblasts develop extremely dense and highly vascularized long bones. Here we
      provide evidence that osteoblasts lacking Vhl overexpress and secrete high levels
      of VEGF, which subsequently promotes the proliferation and osteogenic
      differentiation of bone marrow stromal cells (BMSC) by promoting expression of
      Heme oxygenase-1 (HO-1) in BMSC. Conditioned medium from osteoblasts Vhl (CM-CRE)
      promoted the proliferation and osteogenic differentiation of BMSC, in comparison
      with conditioned medium derived from normal osteoblasts (CM-GFP). Recombinant
      VEGF stimulated the proliferation and osteogenic differentiation of BMSC
      culturing in CM-GFP. By contrast, VEGF-neutralizing antibody inhibited the
      proliferation and osteogenic differentiation of BMSC culturing in CM-CRE.
      Treatment with a HO-1 inhibitor, SnPP, significantly inhibited VEGF-induced BMSC
      proliferation and osteogenic differentiation. On the contrary, activation of HO-1
      with CoPP reversed the suppressing of VEGF-antibody on the proliferation and
      osteogesis of BMSC culturing in CM-CRE. These studies suggest that osteoblasts
      promote the proliferation and osteogenic differentiation of BMCS by VEGF/HO-1
      pathway. 

PMID- 24940622
TI  - The proof is in the eating: subjective peer norms are associated with
      adolescents' eating behaviour.
AB  - OBJECTIVE: To investigate associations of self-perceived eating-related peer
      norms (called 'subjective peer norms') with adolescents' healthy eating
      intentions and intake of healthy and unhealthy food. DESIGN: Cross-sectional data
      were collected in a large international survey. SETTING: Two types of subjective
      peer norms were assessed: perceived peer encouragement of healthy eating and
      perceived peer discouragement of unhealthy eating. Outcome variables were healthy
      eating intentions, intake of healthy food (fruits and vegetables) and intake of
      unhealthy food (snacks and soft drinks). SUBJECTS: Over 2500 European (pre
      )adolescents aged between 10 and 17 years participated. RESULTS: Subjective peer
      norms were associated with all three outcome variables. While both perceived
      encouragement of healthy eating and perceived discouragement of unhealthy eating
      were related to intentions, only peer encouragement of healthy eating was related
      to intakes of both healthy and unhealthy food. CONCLUSIONS: Subjective peer norms
      play a role in adolescent eating behaviour and as such are an important target
      for health promotion. Addressing norms that encourage healthy eating may be more
      promising in changing behaviour than norms that discourage unhealthy eating.

PMID- 24940621
TI  - Comparative genome analysis reveals metabolic versatility and environmental
      adaptations of Sulfobacillus thermosulfidooxidans strain ST.
AB  - The genus Sulfobacillus is a cohort of mildly thermophilic or thermotolerant
      acidophiles within the phylum Firmicutes and requires extremely acidic
      environments and hypersalinity for optimal growth. However, our understanding of
      them is still preliminary partly because few genome sequences are available.
      Here, the draft genome of Sulfobacillus thermosulfidooxidans strain ST was
      deciphered to obtain a comprehensive insight into the genetic content and to
      understand the cellular mechanisms necessary for its survival. Furthermore, the
      expressions of key genes related with iron and sulfur oxidation were verified by
      semi-quantitative RT-PCR analysis. The draft genome sequence of Sulfobacillus
      thermosulfidooxidans strain ST, which encodes 3225 predicted coding genes on a
      total length of 3,333,554 bp and a 48.35% G+C, revealed the high degree of
      heterogeneity with other Sulfobacillus species. The presence of numerous
      transposases, genomic islands and complete CRISPR/Cas defence systems testifies
      to its dynamic evolution consistent with the genome heterogeneity. As expected,
      S. thermosulfidooxidans encodes a suit of conserved enzymes required for the
      oxidation of inorganic sulfur compounds (ISCs). The model of sulfur oxidation in
      S. thermosulfidooxidans was proposed, which showed some different characteristics
      from the sulfur oxidation of Gram-negative A. ferrooxidans. Sulfur oxygenase
      reductase and heterodisulfide reductase were suggested to play important roles in
      the sulfur oxidation. Although the iron oxidation ability was observed, some key
      proteins cannot be identified in S. thermosulfidooxidans. Unexpectedly, a
      predicted sulfocyanin is proposed to transfer electrons in the iron oxidation.
      Furthermore, its carbon metabolism is rather flexible, can perform the
      transformation of pentose through the oxidative and non-oxidative pentose
      phosphate pathways and has the ability to take up small organic compounds. It
      encodes a multitude of heavy metal resistance systems to adapt the heavy metal
      containing environments. 

PMID- 24940623
TI  - Application of random forests methods to diabetic retinopathy classification
      analyses.
AB  - BACKGROUND: Diabetic retinopathy (DR) is one of the leading causes of blindness
      in the United States and world-wide. DR is a silent disease that may go unnoticed
      until it is too late for effective treatment. Therefore, early detection could
      improve the chances of therapeutic interventions that would alleviate its
      effects. METHODOLOGY: Graded fundus photography and systemic data from 3443
      ACCORD-Eye Study participants were used to estimate Random Forest (RF) and
      logistic regression classifiers. We studied the impact of sample size on
      classifier performance and the possibility of using RF generated class
      conditional probabilities as metrics describing DR risk. RF measures of variable
      importance are used to detect factors that affect classification performance.
      PRINCIPAL FINDINGS: Both types of data were informative when discriminating
      participants with or without DR. RF based models produced much higher
      classification accuracy than those based on logistic regression. Combining both
      types of data did not increase accuracy but did increase statistical
      discrimination of healthy participants who subsequently did or did not have DR
      events during four years of follow-up. RF variable importance criteria revealed
      that microaneurysms counts in both eyes seemed to play the most important role in
      discrimination among the graded fundus variables, while the number of medicines
      and diabetes duration were the most relevant among the systemic variables.
      CONCLUSIONS AND SIGNIFICANCE: We have introduced RF methods to DR classification
      analyses based on fundus photography data. In addition, we propose an approach to
      DR risk assessment based on metrics derived from graded fundus photography and
      systemic data. Our results suggest that RF methods could be a valuable tool to
      diagnose DR diagnosis and evaluate its progression.

PMID- 24940625
TI  - Current nanotechnological strategies for an effective delivery of drugs in
      treatment of periodontal disease.
AB  - Periodontal disease is a localized inflammatory disorder, with tissue destruction
      resulting from the host response to bacterial antigens and irritants. Several
      other risk factors, such as smoking, hormonal changes, diabetes, drugs, disease,
      and genetic factors, play an important role in the progression of periodontal
      disease. This disease results in the formation of periodontal pockets or deepened
      crevices between the gingival and tooth root that produce occasional pain and
      discomfort, impaired mastication, and irreversible tooth loss. The primary
      rationale for controlled, sustained, and targeted drug delivery is necessary to
      achieve better therapeutic outcomes or patient compliance against periodontal
      disease and its various stages. Both systemic (liposomes, microspheres,
      nanoparticles, hydrogels) and local (fibers, patches, films, gels)
      antibiotic/antimicrobial approaches have their important place in periodontal
      therapy. The overall goal of this article is to provide the clinician with
      information related to the pathogenesis, risk, polymer used for drug delivery,
      and current nanotechnological systems for an effective treatment of periodontal
      disease. 

PMID- 24940626
TI  - Recent advances in self-emulsifying drug delivery systems (SEDDS).
AB  - One of the biggest challenges confronting the contemporary drug delivery science
      today is to improve on the oral bioavailability of a vast number of drugs
      exhibiting poor and inconsistent gastrointestinal absorption. Self-emulsifying
      drug delivery systems (SEDDS) have been proved as highly useful technological
      innovations to surmount such bioavailability hiccups by virtue of their
      diminutive globule size, higher solubilization tendency for hydro-phobic drugs,
      robust formulation advantages, and easier scalability in the industrial milieu.
      Besides, these systems are also known to inhibit the P-glycoprotein (P-gp)
      efflux, reduce metabolism by gut Cytochrome P-450 enzymes, and circumnavigate the
      hepatic first-pass effect, facilitating absorption of drugs via intestinal
      lymphatic pathways. In the last two decades, the phenomenal success of SEDDS as a
      potential tool for oral delivery of drugs has extrapolated their applications to
      non-oral delivery also. Various innovative approaches and patented techniques
      have been reported on formulation of diverse oral and non-oral self-emulsifying
      (SE) systems not only of various synthetic and semisynthetic drugs, but also of
      several phytopharmaceuticals, nutraceuticals, and biological macromolecules. Of
      late, an escalating number of reports have been pouring in on special types of SE
      systems, mostly nanosized, employing functional excipients such as polar lipids,
      phospholipids, cellulosic polymer, diblock polymers, etc. This review paper
      provides an updated bird's-eye view account on the publications and patents of
      such novel SE approaches for use in both oral and non-oral therapeutics.
      Providing a relatively pithy overview, this paper thus endeavors to act as a
      repertoire of knowledge and know-how to guide the product development scientist
      in formulating variegated SE systems. 

PMID- 24940627
TI  - High-performance ZnO nanowire transistors with aluminum top-gate electrodes and
      naturally formed hybrid self-assembled monolayer/AlO(x) gate dielectric.
AB  - A method for the formation of a low-temperature hybrid gate dielectric for high
      performance, top-gate ZnO nanowire transistors is reported. The hybrid gate
      dielectric consists of a self-assembled monolayer (SAM) and an aluminum oxide
      layer. The thin aluminum oxide layer forms naturally and spontaneously when the
      aluminum gate electrode is deposited by thermal evaporation onto the SAM-covered
      ZnO nanowire, and its formation is facilitated by the poor surface wetting of the
      aluminum on the hydrophobic SAM. The hybrid gate dielectric shows excellent
      electrical insulation and can sustain voltages up to 6 V. ZnO nanowire
      transistors utilizing the hybrid gate dielectric feature a large transconductance
      of 50 MUS and large on-state currents of up to 200 MUA at gate-source voltages of
      3 V. The large on-state current is sufficient to drive organic light-emitting
      diodes with an active area of 6.7 mm(2) to a brightness of 445 cd/m(2). Inverters
      based on ZnO nanowire transistors and thin-film carbon load resistors operate
      with frequencies up to 30 MHz.

PMID- 24940624
TI  - Competence of in vitro cultured mouse embryonic stem cells for myogenic
      differentiation and fusion with myoblasts.
AB  - Pluripotent stem cells are a potential source of various cell types for use in
      regenerative medicine. Despite accumulating knowledge, there is currently no
      efficient and reproducible protocol that does not require genetic manipulation
      for generation of myogenic cells from pluripotent stem cells. Here, we examined
      whether mouse embryonic stem (ES) cells are able to undergo myogenic
      differentiation and fusion in response to signals released by differentiating
      myoblasts. Using ES cells expressing the histone 2B-green fluorescent fusion
      protein, we were able to detect hybrid myotubes formed by ES cells and
      differentiating myoblasts. ES cells that fused with myoblasts downregulated the
      expression of pluripotency markers and induced the expression of myogenic
      markers, while unfused ES cells did not exhibit this expression pattern. Thus,
      the signals released by myoblasts were not sufficient to induce myogenic
      differentiation of ES cells. Although ES cells synthesize many proteins involved
      in myoblast adhesion and fusion, we did not observe any myotubes formed
      exclusively by ES cells. We found that ES cells lacked M-cadherin and vascular
      cell adhesion molecule-1, which may account for the low frequency of hybrid
      myotube formation in ES cell-myoblast co-cultures and the inability of ES cells
      alone to form myotubes. 

PMID- 24940629
TI  - Anodized indium metal electrodes for enhanced carbon dioxide reduction in aqueous
      electrolyte.
AB  - The interactions of CO2 with indium metal electrodes have been characterized for
      electrochemical formate production. The electrode oxidation state, morphology,
      and voltammetric behaviors were systematically probed. It was found that an
      anodized indium electrode stabilized formate production over time compared to
      etched indium electrodes and indium electrodes bearing a native oxide in applied
      potential range of -1.4 to -1.8 V vs SCE. In addition, it was observed that
      formate is the major product at unprecedentedly low overpotentials at the
      anodized surface. A surface hydroxide species was observed suggesting a mechanism
      of formate production that involves insertion of CO2 at the indium interface to
      form an electroactive surface bicarbonate species. 

PMID- 24940628
TI  - Clinical features associated with suicide attempts versus suicide gestures in an
      inpatient sample.
AB  - The objective of this study was to test whether suicide attempters and suicide
      gesturers can be clinically differentiated. A total of 150 subjects who had
      attempted suicide at least once, had made a suicide gesture, had suicidal
      ideation, and/or had engaged in non-suicidal self-injury were recruited from the
      inpatient service of the Jimenez Diaz Foundation (Madrid, Spain). A multinomial
      regression analysis was conducted. Histrionic and antisocial personality
      disorders were risk factors specific to suicide gestures. Narcissistic
      personality disorder was specifically associated with suicide attempts.
      Borderline personality disorder was associated with both suicide gestures and
      attempts. A high level of impulsiveness was a risk factor specific to suicide
      attempts. CONCLUSION: Suicide attempters and suicide gesturers are two distinct,
      although partially overlapping, populations.

PMID- 24940630
TI  - [Limits to arthroscopic treatment of degenerative triangular fibrocartilage
      complex lesions depending on the ulnar variance].
AB  - PURPOSE: The present prospective study investigated the influence of the static
      ulnar variance on the success of arthroscopic debridement of degenerative TFCC
      lesions. PATIENTS AND METHODS: 10 patients with an ulnar positive variance
      ("Ulna+") and 12 patients with ulnar neutral or ulnar negative variance ("Ulna
      /0") were examined preoperatively (U0), as well as at 2 (U2) and 6 (U6) months
      after arthroscopic debridement of degenerative TFCC lesions and compared with
      each other. After the U2 investigation due to persistent complaints in 9 of 10
      patients with an ulnar positive variance there was a need for further surgery,
      consisting of ulnar shortening osteotomy (USO). The following parameters were
      recorded in each case: pain at rest and with load, the summed wrist range of
      motion - consisting of extension and flexion, radial and ulnar deviation,
      pronation and supination - compared to the contralateral side, the strength of
      the affected hand compared to the contralateral side, the Mayo modified wrist
      score (MMWS), the Krimmer score and the DASH score. Preoperatively there were no
      significant differences between the 2 cohorts "Ulna+" and "Ulna-/0" except for
      the characteristic "pain at rest". RESULTS: At 2 months postoperatively (U2), the
      results in the cohort "Ulna+" remained at a significantly or tendentially poorer
      level compared to the cohort "Ulna-/0". The subsequent surgical treatment of the
      subgroup "Ulna+" with USO led to almost complete approximation of the results at
      6 months postoperatively (U6). In addition to this, with time (U6) within each
      subgroup there were tendential or significant improvements of all characteristics
      compared to the preoperative situation (U0). At U6 four of 22 patients were 
      unable to work. CONCLUSION: Degenerative lesions of the TFCC can be treated
      successfully by arthroscopic debridement in cases of ulnar negative and ulnar
      neutral variance. Patients with ulnar positive variance and persistent complaints
      after debridement of the TFCC can be treated successfully with a secondary ulnar
      shortening osteotomy.

PMID- 24940631
TI  - [Median nerve neuropathy after perilunate dislocation injuries].
AB  - PURPOSE: The purpose of this retrospective study was to investigate the frequency
      and appearance of median nerve neuropathy following perilunate dislocation
      injuries with respect to the preceding surgical decompression and the clinical
      outcome. PATIENTS AND METHODS: 32 patients were followed for a mean of 65 months
      after surgery for perilunate dislocation, including carpal tunnel release in 13
      patients. 10 of 11 patients with clinical symptoms of median nerve affection at
      follow-up had additionally an electrophysiological examination. Median neuropathy
      was assumed if 2 or more parameters were pathologic. Patients with and without
      median neuropathy were compared. The DASH score, pain, wrist motion, grip
      strength and the Mayo wrist score were used to rate the outcome. RESULTS: In 6
      patients, neuropathy of the median nerve persisted since injury in spite of
      carpal tunnel release in 5 of them. 3 patients showed secondary, delayed median
      nerve affection. Patients with median neuropathy had a worse result with regard
      to pain at rest, grip force, the DASH score, and the Mayo wrist score. The
      difference was statistically significant for pain with activities. CONCLUSION:
      Median neuropathy following perilunar dislocation injuries is frequent. It
      appears rather like a chronic neural lesion than a typical compression syndrome.
      A primary carpal tunnel release cannot always prevent persistent neural
      disorders.

PMID- 24940632
TI  - [Commentary on: Strobel U, Tami I, Andreisek G, et al. Comparison of functional
      results with MRI findings after surgical treatment of transscaphoid perilunate
      fracture dislocations of the wrist: the role of scapholunate ligament lesions].

PMID- 24940633
TI  - [Operative treatment of rhizarthrosis with trapezectomy and suspension of the
      first metacarpal with a Mini TightRope(r)].
AB  - PURPOSE: The aim of this work was to examine the utility of the Mini
      TightRope((r)) after trapezectomy and suspension of the first metacarpal in cases
      of clinically manifest rhizarthrosis. PATIENTS AND METHOD: 31 Patients (26
      female, 5 male, mean age 57.9 years) with primary rhizarthrosis were treated with
      a trapezectomy and suspension of the first metacarpal with a Mini TightRope((r))
      (cost 225 Euro). In the course of a retrospective study, all patients underwent a
      clinical and radiological re-examination at an average of 13.5 (6-22) months. To
      assess the therapy, a clinical and radiological examination as well as the score
      of Buck-Gramcko were used. RESULTS: 74.2% of the patients obtained good and very
      good results, 12.9% achieved satisfactory or poor outcomes. In 2 patients the
      Mini Tight-Rope((r)) had to be removed due to a proximalisation of the first
      metacarpal and strong pain in rest and motion after 6-7 months. Whereas the
      distance between the distal scaphoid pole and the base of the first metacarpal
      postoperatively averaged 11.1 (8-14) mm, it averaged 5.3 (0-10.2) mm in the
      follow-up examination. CONCLUSION: With the presented procedure it is possible to
      achieve in the majority of the treated patients good and very good results. 2
      early removals of the implants, a documented proximalisation in spite of the
      implant and the price of the Mini TightRope((r)) of currently 225 Euro need to be
      discussed critically.

PMID- 24940634
TI  - Modified proximal interphalangeal joint palmar plate arthroplasty after fracture
      dislocation: a case report.
AB  - We present the results of treatment of a neglected fracture of the base of the
      middle phalanx of the ring finger, with dorsal proximal interphalangeal joint
      dislocation. A modified palmar plate arthroplasty technique was used with the
      removal of bony remnants and non-anatomic palmar plate insertion to the fracture
      site. At one-year follow-up the patient showed excellent recovery with an active
      range of motion of the ring finger of 290 degrees  (93% of the other side),
      strong total grip (48 kg) and a quick DASH score of 11. X-ray images showed
      perfect re-building of the palmar lip of the base of the middle phalanx with no
      signs of arthritis. Other options for the treatment of acute and chronic PIP
      joint fracture dislocations are discussed. 

PMID- 24940635
TI  - Seasonal trends in intrapack aggression of captive wolves (Canis lupus) and wolf
      dog crosses: implications for management in mixed-subspecies exhibits.
AB  - Mixed-species exhibits are becoming increasingly common in the captive management
      of a wide range of species. Systematic evaluations of enclosures consisting of
      multiple subspecies, however, are relatively infrequent. The aim of this study
      was to measure seasonal trends in aggressive behaviors within a captive pack of
      wolves and wolf-dog crosses in a sanctuary setting. The frequency of intrapack
      social behaviors occurring within scan-sampling intervals was recorded for wolves
      and wolf-dog crosses during autumn, winter, and spring (2008-2009). Both
      subspecies displayed distinct seasonal trends in aggression. Wolf-dog crosses
      exhibited overall higher levels of aggression than wolves, although these
      instances were mostly noncontact and no significant differences were observed in
      the relative frequencies of aggressive behaviors between subspecies during any
      season. These findings suggest that wolves and wolf-dog crosses may be housed
      successfully given continuous behavioral monitoring, and these findings represent
      the first empirical account of wolf-dog cross behavior directly compared to
      wolves. Future studies should be conducted with similar packs to determine if
      this dynamic is universal. Such research will aid in the development of
      management and welfare strategies for captive facilities that provide permanent
      residences for wolves and wolf-dog crosses. 

PMID- 24940636
TI  - Cesarean delivery and risk of inflammatory bowel disease: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: It has been considered that cesarean delivery is a risk factor for the
      two subtypes of inflammatory bowel diseases (IBDs): Crohn's disease (CD) and
      ulcerative colitis (UC). The aim of this meta-analysis was to examine the
      relationship between cesarean delivery and the development of IBD. MATERIAL AND
      METHODS: We searched the articles retrieved by PubMed, MEDLINE and EMBASE
      databases to identify observational studies regarding the relationship between
      cesarean section and the development of CD and/or UC. Pooled odds ratios were
      calculated for each relationship. RESULTS: Nine studies evaluated the potential
      association between cesarean delivery and the development of IBD and met all of
      our inclusion criteria. The pooled data from six included studies indicated
      cesarean delivery was a risk factor for CD (95% confidence interval [CI]: 1.12
      1.70; p = 0.003). Likewise, we observed a positive association between cesarean
      delivery and pediatric CD (95% CI: 1.06-1.35; p = 0.005). However, results from
      the four included studies for UC indicated the rate of cesarean section in UC
      patients was not higher than that of control subjects (95% CI: 0.87-1.32; p =
      0.54). Overall, we did not observe a positive relationship between cesarean
      delivery and IBD (95% CI: 0.99-1.30; p = 0.08). CONCLUSION: Results of this meta
      analysis support the hypothesis that cesarean delivery was associated with the
      risk of CD but not of UC. The total rate of cesarean delivery of IBD patients was
      similar with that of control subjects.

PMID- 24940637
TI  - Analytical performance of the VITROS(r) Immunodiagnostic Products total PSA II
      and free PSA assays.
AB  - OBJECTIVES: To assess the precision and the performance of the VITROS((r)) total
      PSA II (tPSA) and free PSA (fPSA) assays on the VITROS((r)) ECi/ECiQ
      Immunodiagnostic system. DESIGN AND METHODS: The precision of the tPSA and fPSA
      assays was evaluated following the Clinical and Laboratory Standards Institute
      (CLSI)-guideline EP5-A2. During a 20-day period, 2 runs of 5 quality control (QC)
      samples were performed daily. Results of tPSA (n=292) and fPSA (n=289) were
      compared between VITROS((r)) ECi/ECiQ Immunodiagnostic system and Roche Cobas
      8000 e602 system (Cobas tPSA and fPSA assays). A modified CLSI-guideline EP9-A2
      was used to correlate the results based on a Deming regression correlation study.
      RESULTS: A within-run and within-calibration imprecision of <=2% was obtained for
      all 5 QC concentration levels for both tPSA and fPSA. Method comparison revealed
      a constant bias of 17% for tPSA and 6% for fPSA. These values are within the
      desirable bias of 18.7% suggested by the Westgard Biological Variation Database
      Specifications. A high agreement was found between the two methods, with
      correlation coefficients of 0.997 and 0.993 for tPSA and fPSA respectively.
      CONCLUSION: The VITROS((r)) tPSA and fPSA assays showed an excellent precision
      and bias and a good correlation with the Roche method.

PMID- 24940639
TI  - Discrimination of leucine and isoleucine in peptides sequencing with Orbitrap
      Fusion mass spectrometer.
AB  - An efficient approach to easy and reliable differentiation between isomeric
      leucine and isoleucine in peptide sequencing utilizes multistage electron
      transfer dissociation and higher energy collision activated dissociation in the
      Orbitrap Fusion mass spectrometer. The MS(3) method involves production and
      isolation of primary odd-electron z(*) ions, followed by radical site initiation
      of their fragmentation with formation of w-ions, characteristic of the isomeric
      amino acid residues. Six natural nontryptic peptides isolated from the secretion
      of frog Rana ridibunda were studied. Their lengths were in the range between 15
      and 37 amino acids and the number of targeted isomeric (Leu/Ile) residues varied
      between 1 and 7. The experiments were successful in all 22 cases of Leu/Ile
      residues, leaving no doubts in identification. The method is extremely selective
      as the targeted w-ions appear to be the most intense in the spectra. The proposed
      approach may be incorporated into shotgun proteomics algorithms and allows for
      the development of an exclusively mass spectrometric method for automated
      complete de novo sequencing of various peptides and proteins. 

PMID- 24940640
TI  - Prodrug-inspired probes selective to cathepsin B over other cysteine cathepsins.
AB  - Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic
      target or biomarker for several diseases including aggressive cancer, arthritis,
      and parasitic infections. The development of probes capable of assessing CTB
      activity in cell lysates, living cells, and animal models of disease are needed
      to understand its role in disease progression. However, discovering probes
      selective to cathepsin B over other cysteine cathepsins is a significant
      challenge due to overlap of preferred substrates and binding site homology in
      this family of proteases. Herein we report the synthesis and detailed evaluation
      of two prodrug-inspired fluorogenic peptides designed to be efficient and
      selective substrate-based probes for CTB. Through cell lysate and cell assays, a
      promising lead candidate was identified that is efficiently processed and has
      high specificity for CTB over other cysteine cathepsins. This work represents a
      key step toward the design of rapid release prodrugs or substrate-based molecular
      imaging probes specific to CTB. 

PMID- 24940641
TI  - Surface-dominated transport on a bulk topological insulator.
AB  - Topological insulators are guaranteed to support metallic surface states on an
      insulating bulk, and one should thus expect that the electronic transport in
      these materials is dominated by the surfaces states. Alas, due to the high
      remaining bulk conductivity, it is challenging to achieve surface-dominated
      transport. Here we use nanoscale four-point setups with a variable contact
      distance on an atomically clean surface of bulk-insulating Bi2Te2Se. We show that
      the transport at 30 K is two-dimensional rather than three-dimensional, that is,
      surface-dominated, and we find a surface state mobility of 390(30) cm(2) V(-1) s(
      1) at 30 K at a carrier concentration of 8.71(7) * 10(12) cm(-2).

PMID- 24940638
TI  - miR-31 dysregulation in cystic fibrosis airways contributes to increased
      pulmonary cathepsin S production.
AB  - RATIONALE: Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage
      (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to
      lung inflammation via degradation of antimicrobial proteins, such as lactoferrin
      and members of the beta-defensin family. OBJECTIVES: In this study, we
      investigated the hypothesis that airway epithelial cells are a source of CTSS,
      and mechanisms underlying CTSS expression in the CF lung. METHODS: Protease
      activity was determined using fluorogenic activity assays. Protein and mRNA
      expression were analyzed by ELISA, Western blotting, and reverse-transcriptase
      polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: In contrast to
      neutrophil elastase, CTSS activity was detectable in 100% of CF BAL fluid samples
      from patients without Pseudomonas aeruginosa infection. In this study, we
      identified epithelial cells as a source of pulmonary CTSS activity with the
      demonstration that CF airway epithelial cells express and secrete significantly
      more CTSS than non-CF control cells in the absence of proinflammatory
      stimulation. Furthermore, levels of the transcription factor IRF-1 correlated
      with increased levels of its target gene CTSS. We discovered that miR-31, which
      is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating
      CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels
      with concomitant knockdown of CTSS expression and secretion. CONCLUSIONS: The miR
      31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung
      disease and may open up new avenues for exploration in the search for an
      effective therapeutic target.

PMID- 24940642
TI  - Protein content of antivenoms and relationship with their immunochemical
      reactivity and neutralization assays.
AB  - CONTEXT: Therapy for snakebites relies on the application of antivenoms, which
      may be produced with different immunogenic mixtures of venom and possess
      different pharmaceutical characteristics. For these reasons, immunological cross
      reactivity and heterologous neutralization were analyzed relative to the protein
      content of three antivenoms used in the Americas. METHODS: The antivenoms studied
      were composed of equine F(ab')2 fragments from animals immunized with Crotalinae
      venoms. The antivenoms were tested against venoms of seven pit viper species from
      Argentina, seven from Mexico, one from Costa Rica, and one from Colombia.
      RESULTS: Immunoblotting showed high cross-reactivity of all major protein bands
      with all the antivenoms tested. ELISA results also showed high cross-reactivity
      among the different venoms and antivenoms, and a high heterologous neutralization
      was observed. The results can be interpreted in different ways depending on
      whether the reactivity is considered in terms of the volume of antivenom used or
      by the amount of protein contained in this volume of antivenom. The antivenoms
      with high immunochemical reactivity and neutralizing capacity were those with
      higher protein content per vial; but when doses were adjusted by protein content,
      antivenoms of apparently lower neutralizing capacity and immunochemical
      reactivity showed at least similar potency and reactivity although volumetrically
      at higher doses. CONCLUSION: Protein content relative to neutralization potency
      of different products must be taken into account when antivenoms are compared, in
      addition to the volume required for therapeutic effect. These results show the
      importance of obtaining high-affinity and high-avidity antibodies to achieve good
      neutralization using low protein concentration and low-volume antivenoms.

PMID- 24940643
TI  - Pharmacokinetics and pharmacodynamics of the myotoxic venom of Pseudechis
      australis (mulga snake) in the anesthetised rat.
AB  - CONTEXT: Myotoxicity is a common clinical effect of snake envenoming and results
      from either local or systemic myotoxins in snake venoms. Although numerous
      myotoxins have been isolated from snake venoms, there has been limited study on
      the relationship between the time course of venom concentrations
      (pharmacokinetics) and the time course of muscle injury measured as a rise in
      creatine kinase (CK) (pharmacodynamics). OBJECTIVE: The aim of this study was to
      develop an in vivo model of myotoxicity to investigate the time course of
      myotoxicity and the effect of antivenom. MATERIALS AND METHODS: Anesthetised rats
      were administered Pseudechis australis (mulga snake) venom either through i.v.,
      i.m. or s.d. route, including a range of doses (5-100 MUg/kg). Serial blood
      samples were collected for measurement of venom using enzyme immunoassay and
      measurement of CK and creatinine. Antivenom was administered before, 1 and 6 h
      after venom administration to investigate its effect on muscle injury. Plots of
      venom and CK versus time were made and the area under the curve (AUC) was
      calculated. RESULTS: There was a significant dose-dependent increase in CK
      concentration after administration of P. australis venom, which was greatest for
      i.v. administration. Timed measurement of venom concentrations showed a rapid
      absorption through s.d. and i.m. routes and a delayed rise in CK concentrations
      following any route. Antivenom prevented myotoxicity shown by a decrease in the
      CK AUC, which was most effective if given earliest. There was a rise in
      creatinine following i.v. venom administration. CONCLUSION: The study shows the
      delayed relationship between venom absorption and the rise in CK, consistent with
      the delayed onset of myotoxicity in human envenoming. Antivenom prevented
      myotoxicity more effectively if given earlier.

PMID- 24940644
TI  - Shiitake dermatitis recorded by French Poison Control Centers - new case series
      with clinical observations.
AB  - CONTEXT: Shiitake (Lentinula edodes) is an edible mushroom which was initially
      grown in Japan and China and is now sold on the European market. Flagellate
      erythema may arise following shiitake consumption and was first described in
      Japan in 1974. OBJECTIVE: This paper reports a French shiitake dermatitis case
      series. METHODS: The findings of retrospective study of shiitake dermatitis
      cases, reported to French Poison Control Centres (PCC) from January 2000 to
      December 2013, are reported. RESULTS: Among 32 exposed patients, 15 presented
      flagellate urticarial lesions after raw shiitake consumption. The first case of
      this series was reported in 2006 and the last nine cases were reported as of
      2012. After shared meals, no symptoms were reported among guests, who preferred
      cooked shiitake to the raw mushroom. In this series, rashes appeared 12 h to 5
      days (median: 24 h) after raw shiitake ingestion. Linear and itchy urticarial
      lesions formed on the trunk, arms, and legs within a few hours and persisted for
      3-21 days. In four cases, rash and pruritus were either triggered or worsened by
      sun exposure. Eleven patients received corticosteroids, antihistamines, or both.
      All patients completely recovered. CONCLUSION: Due to the rapidly increasing
      consumption of exotic food in Western countries, it is no surprise that cases of
      shiitake dermatitis are now appearing in Europe. The mechanism of shiitake
      dermatitis is thought to be toxic and due to lentinan, a polysaccharide component
      of the mushroom. There is no specific validated treatment for shiitake
      dermatitis. Health professionals and the general population should be aware of
      both the risk associated with raw shiitake consumption and of the good prognosis
      of this very spectacular and uncomfortable toxic dermatitis.

PMID- 24940645
TI  - Compartment syndrome after South American rattlesnake (Crotalus durissus
      terrificus) envenomation.
AB  - CONTEXT: In order to report the outcome of a patient who developed compartment
      syndrome after South American rattlesnake (Crotalus durissus terrificus)
      envenomation, confirmed by subfascial pressure measurement and magnetic resonance
      imaging (MRI). CASE DETAILS: A 63-year-old male was admitted 1 h after being
      bitten on the right elbow by a "large" snake, which was not brought for
      identification. Physical and laboratory features upon admission revealed two fang
      marks, local tense swelling, paresthesia, intense local pain, hypertension,
      coagulopathy, and CK = 1530 U/L (RV < 170 U/L). The case was initially treated
      with bothropic antivenom (80 mL, intravenously), with no improvement. Evolution
      within 13-14 h post-bite revealed generalized myalgia, muscle weakness, palpebral
      ptosis, and severe rhabdomyolysis (CK = 126,160 U/L) compatible with envenoming
      by C. d. terrificus. The patient was then treated with crotalic antivenom (200
      mL, intravenously), fluid replacement, and urine alkalinization. Twenty-four-hour
      post-bite MRI showed marked muscular edema in the anterior compartment of the
      right forearm, with a high subfascial pressure (40 mmHg) being detected 1 h
      later. ELISA of a blood sample obtained upon admission, before antivenom
      infusion, revealed a high serum concentration of C. d. terrificus venom. No
      fasciotomy was performed and the patient was discharged seven days later without
      sequelae. CONCLUSION: Snakebite by C. d. terrificus with subfascial venom
      injection may lead to increased intracompartmental pressure.

PMID- 24940646
TI  - Cardiac arrest after ibogaine ingestion.

PMID- 24940647
TI  - AV block II in a toddler after ingestion of a single tablet fingolimod.

PMID- 24940648
TI  - Response to letter to the Editor regarding "A note on Conium maculatum L., the
      plant that defeated Alexander the Great" in Clinical Toxicology 2014: (doi:
      10.3109/15563650.2013.870341).

PMID- 24940649
TI  - Cadherin 11, a miR-675 target, induces N-cadherin expression and epithelial
      mesenchymal transition in melasma.
AB  - Cadherin 11 (CDH11) was identified as a target of miR-675 by using a luciferase
      reporter assay. CDH11 expression and miR-675 expression were inversely
      correlated. CDH11 expression was not detected in melanocytes, but CDH11
      expression in fibroblasts and keratinocytes positively influenced melanogenesis
      via the canonical Wnt and AKT activation pathways in cocultured melanocytes.
      CDH11 in fibroblasts or keratinocytes induced N-cadherin and Twist1 expression,
      while decreasing E-cadherin expression. This suggests a role for CDH11 in
      epithelial-mesenchymal transition. CDH11 in fibroblasts also induced the
      migration of cocultured melanocytes. N-cadherin knockdown abolished the
      tyrosinase expression that was induced in CDH11-overexpressing fibroblasts.
      Collectively, our data indicate that CDH11 in fibroblasts and keratinocytes is a
      target of miR-675, and could be involved in melanogenesis through the induction
      of N-cadherin during epithelial-mesenchymal transition. 

PMID- 24940650
TI  - Interaction of plectin with keratins 5 and 14: dependence on several plectin
      domains and keratin quaternary structure.
AB  - Plectin, a cytolinker of the plakin family, anchors the intermediate filament
      (IF) network formed by keratins 5 and 14 (K5/K14) to hemidesmosomes, junctional
      adhesion complexes in basal keratinocytes. Genetic alterations of these proteins
      cause epidermolysis bullosa simplex (EBS) characterized by disturbed
      cytoarchitecture and cell fragility. The mechanisms through which mutations
      located after the documented plectin IF-binding site, composed of the plakin
      repeat domain (PRD) B5 and the linker, as well as mutations in K5 or K14, lead to
      EBS remain unclear. We investigated the interaction of plectin C terminus,
      encompassing four domains, the PRD B5, the linker, the PRD C, and the C
      extremity, with K5/K14 using different approaches, including a rapid and
      sensitive fluorescent protein-binding assay, based on enhanced green fluorescent
      protein-tagged proteins (FluoBACE). Our results demonstrate that all four plectin
      C-terminal domains contribute to its association with K5/K14 and act
      synergistically to ensure efficient IF binding. The plectin C terminus
      predominantly interacted with the K5/K14 coil 1 domain and bound more extensively
      to K5/K14 filaments compared with monomeric keratins or IF assembly
      intermediates. These findings indicate a multimodular association of plectin with
      K5/K14 filaments and give insights into the molecular basis of EBS associated
      with pathogenic mutations in plectin, K5, or K14 genes. 

PMID- 24940651
TI  - Killing two birds with one stone: oral tofacitinib reverses alopecia universalis
      in a patient with plaque psoriasis.

PMID- 24940652
TI  - The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a
      dry-skin mouse model.
AB  - Epidermal hyperinnervation, which is thought to underlie intractable pruritus,
      has been observed in patients with atopic dermatitis (AD). The epidermal
      expression of axonal guidance molecules has been reported to regulate epidermal
      hyperinnervation. Previously, we showed that the excimer lamp has
      antihyperinnervative effects in nonpruritic dry-skin model mice, although
      epidermal expression of axonal guidance molecules was unchanged. Therefore, we
      investigated the antipruritic effects of excimer lamp irradiation and its
      mechanism of action. A single irradiation of AD model mice significantly
      inhibited itch-related behavior 1 day later, following improvement in the
      dermatitis score. In addition, irradiation of nerve fibers formed by cultured
      dorsal root ganglion neurons increased bleb formation and decreased nerve fiber
      expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting
      degenerative changes in these fibers. We also analyzed whether attaching a cutoff
      excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered
      hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA
      damage marker, in dry-skin model mice. Irradiation with COF decreased CPD
      production in keratinocytes, as well as having an antihyperinnervative effect,
      indicating that the antipruritic effects of excimer lamp irradiation with COF are
      due to induction of epidermal nerve degeneration and reduced DNA damage. 

PMID- 24940653
TI  - CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in
      human melanoma cells.
AB  - The CD63 tetraspanin is highly expressed in the early stages of melanoma and
      decreases in advanced lesions, suggesting it as a possible suppressor of tumor
      progression. We employed loss- and gain-of-gene-function approaches to
      investigate the role of CD63 in melanoma progression and acquisition of the
      epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma
      cell lines derived from primary tumors and one primary human melanoma cell line
      isolated from a cutaneous metastasis, differing by levels of CD63 expression.
      CD63-silenced melanoma cells showed enhanced motility and invasiveness with
      downregulation of E-cadherin and upregulation of N-cadherin and Snail. In
      parallel experiments, transient and stable ectopic expression of CD63 resulted in
      a robust reduction of cell motility, invasiveness, and protease activities, which
      was proportional to the increase in CD63 protein level. Transfected cells
      overexpressing the highest level of CD63 when transplanted into immunodeficient
      mice showed a reduced incidence and rate of tumor growth. Moreover, these cells
      showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant
      resistance to undergo an EMT program both in basal condition and in the following
      stimulation with TGFbeta. Thus, our results establish a previously unreported
      mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma. 

PMID- 24940655
TI  - The clinical endocrinology workforce: current status and future projections of
      supply and demand.
AB  - CONTEXT: Many changes in health care delivery, health legislation, and the
      physician workforce that affect the supply and demand for endocrinology services
      have occurred since the first published workforce study of adult endocrinologists
      in 2003. OBJECTIVE: The objective of the study was to assess the current adult
      endocrinology workforce data and provide the first analysis of the pediatric
      endocrinology workforce and to project the supply of and demand for
      endocrinologists through 2025. DESIGN: A workforce model was developed from an
      analysis of proprietary and publicly available databases, consultation with a
      technical expert panel, and the results of an online survey of board-certified
      endocrinologists. PARTICIPANTS: The Endocrine Society commissioned The Lewin
      Group to estimate current supply and to project gaps between supply and demand
      for endocrinologists. A technical expert panel of senior endocrinologists
      provided context, clinical information, and direction. MAIN OUTCOME MEASURES: The
      following were measured: 1) the current adult and pediatric endocrinology
      workforce and the supply of and demand for endocrinologists through 2025 and 2)
      the number of additional entrants into the endocrinology work pool that would be
      required to close the gap between supply and demand. RESULTS: Currently there is
      a shortage of approximately 1500 adult and 100 pediatric full-time equivalent
      endocrinologists. The gap for adult endocrinologists will expand to 2700 without
      an increase in the number of fellows trained. An increase in the prevalence of
      diabetes mellitus further expands the demand for adult endocrinologists. The gap
      can be closed in 5 and 10 years by increasing the number of fellowship positions
      by 14.4% and 5.5% per year, respectively. The gap between supply and demand for
      pediatric endocrinologists will close by 2016, and thereafter an excess supply
      over demand will develop at the current rate of new entrants into the work force.
      CONCLUSIONS: There are insufficient adult endocrinologists to satisfy current and
      future demand. A number of proactive strategies need to be instituted to mitigate
      this gap.

PMID- 24940654
TI  - Knockdown of filaggrin in a three-dimensional reconstructed human epidermis
      impairs keratinocyte differentiation.
AB  - Atopic dermatitis is a chronic inflammatory skin disorder characterized by
      defects in the epidermal barrier and keratinocyte differentiation. The expression
      of filaggrin, a protein thought to have a major role in the function of the
      epidermis, is downregulated. However, the impact of this deficiency on
      keratinocytes is not really known. This was investigated using lentivirus
      mediated small-hairpin RNA interference in a three-dimensional reconstructed
      human epidermis (RHE) model, in the absence of other cell types than
      keratinocytes. Similar to what is known for atopic skin, the experimental
      filaggrin downregulation resulted in hypogranulosis, a disturbed corneocyte
      intracellular matrix, reduced amounts of natural moisturizing factor components,
      increased permeability and UV-B sensitivity of the RHE, and impaired keratinocyte
      differentiation at the messenger RNA and protein levels. In particular, the
      amounts of two filaggrin-related proteins and one protease involved in the
      degradation of filaggrin, bleomycin hydrolase, were lower. In addition, caspase
      14 activation was reduced. These results demonstrate the importance of filaggrin
      for the stratum corneum properties/functions. They indicate that filaggrin
      downregulation in the epidermis of atopic patients, either acquired or innate,
      may be directly responsible for some of the disease-related alterations in the
      epidermal differentiation program and epidermal barrier function. 

PMID- 24940656
TI  - Effectiveness of integrated multidisciplinary rehabilitation in primary brain
      cancer survivors in an Australian community cohort: a controlled clinical trial.
AB  - OBJECTIVE: To evaluate effectiveness of a multidisciplinary rehabilitation
      program for persons following definitive primary brain tumour treatment in a
      community cohort. METHODS: The brain tumour (glioma) survivors (n = 106) were
      allocated either to the treatment group (n = 53) (intensive ambulatory
      multidisciplinary rehabilitation), or the waitlist control group (n = 53). The
      primary outcome - Functional Independence Measure (FIM), measured 'Activity'
      limitation; secondary measures included Depression, Anxiety Stress Scale,
      Perceived Impact Problem Profile and Cancer Rehabilitation Evaluation System.
      Assessments were at baseline, 3 and 6 months after program completion. RESULTS:
      Participants were predominantly women (56%), with mean age 51 years (standard
      deviation 13.6) and median time since diagnosis of 2.1 years. Intention-to-treat
      analysis showed a significant difference between groups at 3-month in favour of
      multidisciplinary rehabilitation program in FIM motor subscales: 'self-care',
      'sphincter', 'locomotion', 'mobility'(p < 0.01 for all); and FIM 'communication'
      (p < 0.01) and 'psychosocial' subscales (p < 0.05), with small to moderate effect
      size (r = 0.2-0.4). At 6-month follow-up, significant improvement in the
      treatment group was maintained only for FIM 'sphincter', 'communication' and
      'cognition' subscales (p < 0.01 for all). No difference between groups was noted
      in other subscales. CONCLUSIONS: brain tumour survivors can improve function with
      multidisciplinary rehabilitation, with some gains maintained up to 6 months.
      Evidence for specific interventions in the 'blackbox' of rehabilitation is
      needed.

PMID- 24940657
TI  - The Rosenberg Self-Esteem Scale: a bifactor answer to a two-factor question?
AB  - Despite its long-standing and widespread use, disagreement remains regarding the
      structure of the Rosenberg Self-Esteem Scale (RSES). In particular, concern
      remains regarding the degree to which the scale assesses self-esteem as a
      unidimensional or multidimensional (positive and negative self-esteem) construct.
      Using a sample of 3,862 high school students in the United Kingdom, 4 models were
      tested: (a) a unidimensional model, (b) a correlated 2-factor model in which the
      2 latent variables are represented by positive and negative self-esteem, (c) a
      hierarchical model, and (d) a bifactor model. The totality of results including
      item loadings, goodness-of-fit indexes, reliability estimates, and correlations
      with self-efficacy measures all supported the bifactor model, suggesting that the
      2 hypothesized factors are better understood as "grouping" factors rather than as
      representative of latent constructs. Accordingly, this study supports the
      unidimensionality of the RSES and the scoring of all 10 items to produce a global
      self-esteem score. 

PMID- 24940658
TI  - Biological, mechanical, and technological considerations affecting the longevity
      of intracortical electrode recordings.
AB  - Intracortical electrodes are important tools, with applications ranging from
      fundamental laboratory studies to potential solutions to intractable clinical
      applications. However, the longevity and reliability of the interfaces remain
      their major limitation to the wider implementation and adoption of this
      technology, especially in broader translational work. Accordingly, this review
      summarizes the most significant biological and technical factors influencing the
      long-term performance of intracortical electrodes. In a laboratory setting,
      intracortical electrodes have been used to study the normal and abnormal function
      of the brain. This improved understanding has led to valuable insights regarding
      many neurological conditions. Likewise, clinical applications of intracortical
      brain-machine interfaces offer the ability to improve the quality of life of many
      patients afflicted with high-level paralysis from spinal cord injury, brain stem
      stroke, amyotrophic lateral sclerosis, or other conditions. It is widely
      hypothesized that the tissue response to the electrodes, including inflammation,
      limits their longevity. Many studies have examined and modified the tissue
      response to intracortical electrodes to improve future intracortical electrode
      technologies. Overall, the relationship between biological, mechanical, and
      technological considerations are crucial for the fidelity of chronic electrode
      recordings and represent a presently active area of investigation in the field of
      neural engineering. 

PMID- 24940659
TI  - Technologies for developing ambulatory cough monitoring devices.
AB  - Cough is a prevailing symptom in most lung diseases. While cough sounds
      themselves can be very instrumental in the diagnosis of certain diseases, their
      intensity and frequency also infers the intensity of the particular illness.
      There is an imperative need for a robust system for identifying and analyzing
      cough sounds. In implementing such systems, researchers are confronted with
      technical challenges such as the choice of sensors and methods of signal
      acquisition, the real time analysis of the acquired signals, and the accurate
      identification of cough events, distinguishing them from similar sounds such as
      speech, laughing, throat clearing and sneezing. Previous approaches have employed
      external environmental sensing methods to achieve more accurate detections at the
      expense of mobility, scalability and real-time cough sensing. Alternative
      approaches have proposed wearable cough sensing methods, which, while mobile, can
      often face challenges in terms of robustness and obtrusiveness. In this paper, we
      explore the strengths and shortcomings of the various techniques that have been
      proposed for automatic detection and analysis of cough sounds. We also suggest
      the next steps in furthering the state of the art. 

PMID- 24940660
TI  - Advances in alginate gel microencapsulation of therapeutic cells.
AB  - Rapid developments in the therapeutic applications of genetically engineered
      cells and stem cell research have increased the possibilities of addressing some
      pathologies by grafting therapeutic cells. Immunoprotective encapsulation of such
      therapeutic cells is often essential for their survival and function. Hydrogels
      provide a bioteolerable matrix for cellular encapsulation and support subsequent
      graft survival and function. The naturally occurring marine polysaccharide,
      alginate, is the hydrogel of choice for most applications. However, long-term
      graft survival is affected by the mechanical instability of alginate and adverse
      immune reaction to its grafting. So, a variety of modifications have been
      developed to enhance the physicochemical properties and biotolerance of alginate
      hydrogels. We highlight the developments in alginate hydrogel microencapsulation
      of therapeutic cells. 

PMID- 24940661
TI  - Adipose-derived adult stem cells: available technologies for potential clinical
      regenerative applications in dentistry.
AB  - Tissue homeostasis depends closely on the activity and welfare of adult stem
      cells. These cells represent a promising tool for biomedical research since they
      can aid in treatment and promote the regeneration of damaged organs in many human
      disorders. Adult stem cells indefinitely preserve their ability to self-renew and
      differentiate into various phenotypes; this capacity could be promoted in vitro
      by particular culture conditions (differentiation media) or spontaneously induced
      in vivo by exploiting the biochemical and mechanical properties of the tissue in
      which the stem cells are implanted. Among the different sources of adult stem
      cells, adipose tissue is an attractive possibility thanks to its ready
      availability and the standard extraction techniques at our disposal today. This
      review discusses the isolation, characterization, and differentiation of human
      adipose-derived adult stem cells, as well as regeneration strategies, therapeutic
      uses, and adverse effects of their delivery. In particular, since oral disorders
      (e.g., trauma, erosion, and chronic periodontitis) often cause the loss of dental
      tissue along with functional, phonetic, and aesthetic impairment, this review
      focuses on the application of human adipose-derived adult stem cells, alone or in
      combination with biomaterials, in treating oral diseases. 

PMID- 24940662
TI  - Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU):
      applications in nanotechnology and regenerative medicine.
AB  - The field of nanotechnology and regenerative medicine has been progressing at a
      rapid pace. From theranostic nanoparticles to biomaterials, the possibilities
      seem endless. Researchers at the University College London have developed and
      patented a technology to manufacture a new breed of novel nanocomposite material
      called polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS
      PCU). The enhanced biocompatibility, superior mechanical engineering properties,
      and augmented degradative resistance of POSS-PCU render it capable of functioning
      as a scaffold for bioartificial organs, nanoparticles for biomedical
      applications, and a coating for medical devices. Indeed, POSS-PCU has been used
      in 3 first-in-man studies as a bypass graft, lacrimal duct, and, most notably,
      the world's first synthetic trachea. Our group has a vested interest in the
      development of next-generation smart biomaterials that use nano-inspired
      technologies and mobilize the regenerative capacity of biological systems. Herein
      we provide a concise and authoritative account of the evolution of biomaterials
      research within a University College London and POSS-PCU context, with further
      emphasis on the prospects and challenges involved in driving the future of
      bioartificial organs in tandem with advanced drug delivery systems in the realm
      of nanotechnology and regenerative medicine. 

PMID- 24940663
TI  - Factors determining airway caliber in asthma.
AB  - Airway hyperresponsiveness is a hallmark of asthma in which airways narrow
      excessively in response to an agonist, resulting in difficulty in breathing.
      Constriction of the smooth muscle that spirals around the airways is the
      principle cause of airway narrowing during an asthma attack. It is likely that
      several mechanisms are involved in the development of a hyperresponsive airway in
      asthma. In this review, we focus on the structural and functional aspects that
      govern the narrowing of a single airway within a lung, then we review the current
      understanding of how these factors become altered in a way that leads to the
      airway hyperresponsiveness observed in asthma. We first examine airway caliber as
      a simple equilibrium of forces favoring narrowing and the forces opposing this
      narrowing. We then review the role that the dynamic forces of tidal breathing and
      deep inspirations have across all length scales of the respiratory system; we
      describe an intriguing inconsistency that has arisen from these data. Finally, we
      examine the interaction between airway remodeling and inflammation and their
      roles in health and disease. 

PMID- 24940664
TI  - Proceedings of the 15th International Symposium on Purine and Pyrimidine
      Metabolism in Man, June 9-13, 2013, Madrid, Spain.

PMID- 24940665
TI  - Novel developments in metabolic disorders of purine and pyrimidine metabolism and
      therapeutic applications of their analogs.
AB  - The biennial 15th symposium on Purine and Pyrimidine metabolism was held in
      Madrid, June 2013 (PP13). During the meeting, several novel developments on the
      diagnosis, pathophysiology, and treatment of several inborn errors of purine and
      pyrimidine metabolism were presented. These ranged from new drugs for gout to
      enzyme replacement therapies for mitochondrial diseases. A relatively novel
      aspect in this meeting was the interest in purine and pyrimidine metabolism in
      nonmammalian systems, such as parasites, mycoplasms, and bacteria. Development of
      novel analogs for parasite infections, cardiovascular diseases, inflammatory
      diseases, and cancer were also discussed.

PMID- 24940666
TI  - Efficacy and safety of a urate lowering regimen in primary gout.
AB  - BACKGROUND AND OBJECTIVES: Pharmacologic urate lowering therapy (ULT), at full
      maintenance doses, has been associated with acute gout arthritis (in up to 80% of
      patients). The American College of Rheumatology has recently advocated gradually
      titrating the maintenance dose upward to chosen serum urate target. Few studies
      have examined the efficacy and safety of a ULT in primary gout. PATIENTS AND
      METHODS: The ULT regimen examined included allopurinol (50 mg/day, with increases
      of 50 mg/month up to 300 mg/day) and colchicine, as prophylaxis to prevent acute
      gouty attacks. The efficacy and safety of this regimen was examined in 42
      patients in whom allopurinol was withheld for >=3 months and restarted after this
      assessment and followed up for 12 months. The efficacy and safety of the ULT
      regimen was related to the serum urate decrease and to the incidence of acute
      gout flares, respectively. RESULTS: Fifty-nine patients (mean age 59 years, 56
      men) with primary gout received the gradually titrated ULT regimen. Baseline
      serum urate was (mean+/-SD) 8.4+/-0.8 mg/dL. At 3, 6, 9, and 12 months serum
      urate fell by a mean of 1.8, 2.5, 2.7, and 2.5 mg/dL, respectively (p<0.001). A
      serum urate level<6.0 mg/dL was achieved by 38/59 (64%) patients. During the 12
      months following the start of the ULT we documented 10 acute arthritis episodes
      (17% of patients). CONCLUSIONS: A gradually titrated hypouricemic regimen for 6
      months in patients with primary gout appears to be effective and safe.

PMID- 24940667
TI  - Fenofibrate increases serum creatinine in a patient with familial nephropathy
      associated to hyperuricemia.
AB  - BACKGROUND: Kidney function progressively deteriorates in patients with familial
      juvenile hyperuricemiac nephropathy (FJHN, OMIN 162000) and chronic renal disease
      is commonly associated to dyslipidemia. We report for the first time abrupt renal
      insufficiency in a patient with FJHN and hypertrygliceridemia following
      fenofibrate administration. CASE REPORT: A 53-year-old man was diagnosed
      clinically with FJHN at age 24 years which was subsequently confirmed by
      genotypic analysis of the UMOD gene at age 40 years. His mother and two brothers
      suffered the disease. At that time, renal size and function were normal, as was
      his blood pressure and serum lipids. At age 34 years, serum urate was 8.5 mg/dL
      and creatinine 1.7 mg/dL (GFR, 58 mL/min/1.73 m2). He was treated with
      allopurinol, losartan, and lovastatin. Serum TG levels ranged between 150 and 250
      mg/dL. At age 52 years, serum urate was 4.1 mg/dL, creatinine 3.2 mg/dL, LDLc 99
      mg/dL (atorvastatin 40 mg/d), and TG 275 mg/dL. Fenofibrate (160 mg/d) was added.
      One month later, serum creatinine increased to 4.2 mg/dL and TG decreased to 125
      mg/dL. He did not complain of muscle pain, weakness, or changes in urinary
      frequency or color and rabdomyolysis was discarded. Fenofibrate was withheld and
      three months later serum creatinine decreased to baseline levels (3.2 mg/dL) and
      TG increased to 197 mg/dL. CONCLUSION: To our knowledge, this is the first
      patient with FJHN in whom fenofibrate administration was associated to a further
      impairment in renal function not attributable to rabdomyolysis.

PMID- 24940668
TI  - Metabolic syndrome in primary gout.
AB  - BACKGROUND AND OBJECTIVES: Primary gout has traditionally been associated with
      obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but
      we do not know the prevalence of these vascular risk factors in patients with
      primary gout from a Mediterranean country. PATIENTS AND METHOD: All patients with
      primary gout and 2 or more acute arthritis episodes documented by a physician
      were selected for the study. The diagnosis of MS required >=3 criteria (ATP III).
      Patients were classified in two groups: decreased (underexcretors) and normal
      (normoexcretors) uric acid excretion related to serum urate levels. RESULTS: One
      hundred and four patients (mean age, 59 years; 100 males) with primary gout were
      included in the study. MS was diagnosed in 38 subjects (37%). The most frequent
      triad defining MS was an increased waist circumference, blood pressure, and
      trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was
      significantly higher in patients with the MS (21/38, 55%) as compared with
      subjects without the MS (3/66, 5%; p<0.001). Mean serum urate level in patients
      with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid
      excretion was significantly lower in the former than in the latter (444+/-110
      mg/24-hour/1,73 m2 versus 546+/-221 mg/day/1,73 m2; p=0.009). CONCLUSIONS: The
      condition of the MS occurs in about one-third of the patients with primary gout.
      Increased waist circumference, blood pressure, and triglycerides levels is the
      most frequent MS triad. Diminished urinary uric acid excretion is more severe in
      gout patients with the MS.

PMID- 24940669
TI  - False in vitro and in vivo elevations of uric acid levels in mouse blood.
AB  - Uric acid (UA) levels in mouse blood have been reported to range widely from 0.1
      MUM to 760 MUM. The aim of this study was to demonstrate false in vitro and in
      vivo elevations of UA levels in mouse blood. Male ICR mice were anesthetized with
      pentobarbital (breathing mice) or sacrificed with overdose ether (non-breathing
      mice). Collected blood was dispensed into MiniCollect(r) tubes and incubated in
      vitro for 0 or 30 min at room temperature. After separation of plasma or serum,
      the levels of UA and hypoxanthine were determined using HPLC. From the non
      incubated plasma of breathing mice, the true value of UA level in vivo was 13.5+/
      1.4 MUM. However, UA levels in mouse blood increased by a factor of 3.9 following
      incubation in vitro. This "false in vitro elevation" of UA levels in mouse blood
      after blood sampling was inhibited by allopurinol, a xanthine oxidase inhibitor.
      Xanthine oxidase was converted to UA in mouse serum from hypoxanthine which was
      released from blood cells during incubation. Plasma UA levels from non-breathing
      mice were 19 times higher than those from breathing mice. This "false in vivo
      elevation" of UA levels before blood sampling was inhibited by pre-treatment with
      phentolamine, an alpha-antagonist. Over-anesthesia with ether might induce alpha
      vasoconstriction and ischemia and thus degrade intracellular ATP to UA. For the
      accurate measurement of UA levels in mouse blood, the false in vitro and in vivo
      elevations of UA level must be avoided by immediate separation of plasma after
      blood sampling from anesthetized breathing mice.

PMID- 24940670
TI  - Proteomic analysis to examine the role of matrix proteins in a gouty tophus from
      a patient with recurrent gout.
AB  - To examine the role of matrix proteins in the formation of gouty tophus, we
      analyzed the crystalline components and matrix proteins in a gouty tophus from a
      patient with recurrent gout. Micro-area X-ray diffraction analysis and infrared
      spectroscopy indicated that the tophus was composed of monosodium urate
      monohydrate. Proteomic analysis identified 134 proteins from the tophus as matrix
      proteins. Many proteins relevant to inflammation and host defense were
      identified, and immunoglobulin was detected in all four extracted fractions (KCl,
      formic acid, guanidine-HCl, and ethylenediaminetetraacetic acid) and from many
      spots throughout a broad molecular weight range after electrophoresis. It is
      thought that the process of biological defense including the immunity has
      occurred in the gouty tophus. 

PMID- 24940672
TI  - Hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiencies: HPRT1
      mutations in new Japanese families and PRPP concentration.
AB  - Mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to
      Lesch-Nyhan syndrome, which is characterized by hyperuricemia, severe motor
      disability, and self-injurious behavior, or HPRT-related gout with hyperuricemia.
      Four mutations were detected in two Lesch-Nyhan families and two families with
      partial deficiency since our last report. A new mutation of G to TT
      (c.456delGinsTT) resulting in a frameshift (p.Q152Hfs*3) in exon 3 has been
      identified in one Lesch-Nyhan family. In the other Lesch-Nyhan family, a new
      point mutation in intron 7 (c.532+5G>T) causing splicing error (exon 7 excluded,
      p.L163Cfs*4) was detected. In the two partial deficiency cases with
      hyperuricemia, two missense mutations of p.D20V (c.59A>T) and p.H60R (c.179A>G)
      were found. An increase of erythrocyte PRPP concentration was observed in the
      respective phenotypes and seems to be correlated with disease severity.

PMID- 24940671
TI  - Transcriptomic approach to Lesch-Nyhan disease.
AB  - Lesch-Nyhan disease (LND) is an X-linked metabolic disease caused by various
      mutations in the gene HPRT1 encoding an enzyme of purine metabolism, hypoxanthine
      guanine phosphoribosyltransferase (HPRT). In its most severe form, LND patients
      suffer from overproduction of uric acid along with neurological or behavioural
      difficulties including self-injurious behaviours. To gain more insight into
      pathogenesis, we compared the transcriptome from human LND fibroblasts to normal
      human fibroblasts using a microarray with 60,000 probes corresponding to the
      entire human genome. Using stringent criteria, we identified 25 transcripts whose
      expression was significantly different between LND and control cells. These genes
      were confirmed by quantitative RT-PCR to be dysregulated in LND cells. Moreover,
      bioinformatic analysis of microarray data using gene ontology (GO) highlighted
      clusters of genes displaying biological processes most significantly affected in
      LND cells. These affected genes belonged to specific processes such as cell cycle
      and cell-division processes, metabolic and nucleic acid processes, demonstrating
      the specific nature of the changes and providing new insights into LND
      pathogenesis. 

PMID- 24940673
TI  - HPRT deficiency in Spain: what have we learned in the past 30 years (1984-2013)?
AB  - Since 1984, we have diagnosed at the La Paz University Hospital, Madrid, Spain,
      41 patients with hypoxanthine phosphoribosyltransferase (HPRT) activity
      deficiency. These patients belonged to 34 families. We have also performed
      molecular and enzymatic diagnosis in three patients from India, one from Belgium,
      and three from Colombia. About 1/3 of these patients were followed up at La Paz
      University Hospital at least every year. This fact has allowed us to examine the
      complete spectrum of HPRT deficiency as well as to perform a more accurate
      diagnosis and treatment. In the present review, we also summarized our studies on
      the basis of physiopathology of the neurological manifestation of Lesch Nyhan
      disease (LND). 

PMID- 24940674
TI  - Thirteen years experience with selective screening for disorders in purine and
      pyrimidine metabolism.
AB  - Purine and pyrimidine disorders represent a heterogeneous group with variable
      clinical symptoms and low prevalence rate. In the last thirteen years, we have
      studied urine/plasma specimens from about 1600 patients and we have identified 35
      patients: eight patients with adenylosuccinate lyase deficiency, eight patients
      with hypoxanthine-guanine phosphoribosyltransferase deficiency, one patient with
      purine nucleoside phosphorylase deficiency, ten patients with xanthine
      dehydrogenase deficiency, six patients with molybdenum cofactor deficiency and
      two patients with dihydropyrimidine dehydrogenase deficiency. Despite low
      incidence of these diseases, our findings highlight the importance of including
      the purine and pyrimidine analysis in the selective screening for inborn errors
      of metabolism in specialized laboratories, where amino acid and organic acid
      disorders are simultaneously investigated. 

PMID- 24940675
TI  - 2,8-Dihydroxyadenine urolithiasis: a not so rare inborn error of purine
      metabolism.
AB  - Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic
      disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine
      (DHA) into urine. The low solubility of DHA results in precipitation and
      formation of urinary crystals and kidney stones. The disease can be present as
      recurrent urolithiasis or nephropathy secondary to crystal precipitation into
      renal parenchyma (DHA nephropathy). The diagnostic tools available, including
      stone analysis, crystalluria, and APRT activity in red blood cells, make the
      diagnosis easy to confirm when APRT deficiency is suspected. However, the lack of
      recognition of this metabolic disorder frequently resulted in a delay in
      diagnosis and treatment with grave consequences. The early recognition and
      treatment of APRT deficiency are of crucial importance to prevent irreversible
      loss of renal function. This review summarizes the genetic and metabolic
      mechanisms underlying DHA stones formation and chronic kidney disease, along with
      the issues of diagnosis and management of APRT deficiency. Moreover, we report
      the mutations in the APRT gene responsible for APRT deficiency in 51 French
      patients (43 families) including 22 pediatric cases (18 families) among the 64
      patients identified in the biochemistry laboratories of Necker Hospital, Paris
      (1978-2013). 

PMID- 24940676
TI  - Publisher's note. Identification of a novel synonymous mutation in the human beta
      ureidopropionase gene UPB1 affecting pre-mRNA splicing.
AB  - beta-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway
      and it catalyzes the conversion of N-carbamyl-beta-alanine and N-carbamyl-beta
      aminoisobutyric acid to beta-alanine and beta-aminoisobutyric acid, respectively,
      and ammonia and CO2. To date, only 16 genetically confirmed patients with a
      complete beta-ureidopropionase deficiency have been reported. Here, we report the
      clinical, biochemical, and molecular analysis of a newly identified patient with
      beta-ureidopropionase deficiency. Mutation analysis of the UPB1 gene showed that
      the patient was compound heterozygous for a novel synonymous mutation c.93C>T
      (p.Gly31Gly) in exon 1 and a previously described missense mutation c.977G>A
      (p.Arg326Gln) in exon 9. The in silico predicted effect of the synonymous
      mutation p.Gly31Gly on pre-mRNA splicing was investigated using a minigene
      approach. Wild-type and the mutated minigene constructs, containing the entire
      exon 1, intron 1, and exon 2 of UPB1, yielded different splicing products after
      expression in HEK293 cells. The c.93C>T (p.Gly31Gly) mutation resulted in altered
      pre-mRNA splicing of the UPB1 minigene construct and a deletion of the last 13
      nucleotides of exon 1. This deletion (r.92 104delGCAAGGAACTCAG) results in a
      frame shift and the generation of a premature stop codon (p.Lys32SerfsX31). Using
      a minigene approach, we have thus identified the first synonymous mutation in the
      UPB1 gene, creating a cryptic splice-donor site affecting pre-mRNA splicing.

PMID- 24940677
TI  - Identification of a hypouricemia patient with SLC2A9 R380W, a pathogenic mutation
      for renal hypouricemia type 2.
AB  - Hypouricemia is characterized by low serum uric acid (SUA) levels (<=3.0 mg/dL)
      with complications such as urolithiasis and exercise-induced acute renal failure.
      We have previously reported that urate transporter 1 (URAT1/SLC22A12) and glucose
      transporter 9 (GLUT9/SLC2A9) are causative genes for renal hypouricemia type 1
      (RHUC1) and renal hypouricemia type 2 (RHUC2), respectively. In the series of
      experiments, two families have been revealed to have RHUC2 due to GLUT9 missense
      mutations R198C or R380W, respectively. Thus far, however, no studies have
      reported other RHUC2 families or patients with these pathogenic mutations. This
      study is aimed to find other cases of RHUC2. We performed mutational analyses of
      GLUT9 exon 6 (for R198C) and exon 10 (for R380W) in 50 Japanese hypouricemia
      patients. Patients were analyzed out of a collection of more than 2000 samples
      from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). We
      identified a novel male patient with heterogeneous RHUC2 mutation R380W. The SUA
      of this hypouricemia patient was 2.6 mg/dL, which is similar to that of our
      previous report (SUA: 2.7 mg/dL). This is the second report indicating RHUC2
      patient due to GLUT9 mutation R380W. This mutation occurs in highly conserved
      amino acid motifs and is reported to be an important membrane topology
      determinant. R380W is a dysfunctional mutation which completely diminishes the
      urate transport activities of GLUT9. Our study revealed a second hypouricemia
      patient with GLUT9 R380W, a pathogenic mutation of RHUC2, which may help to
      expand our understanding of RHUC pathogenesis. 

PMID- 24940678
TI  - ABCG2 dysfunction increases the risk of renal overload hyperuricemia.
AB  - ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is
      identified as a high-capacity urate exporter, and its dysfunction has an
      association with serum uric acid levels and gout/hyperuricemia risk. Generally,
      hyperuricemia has been classified into urate "overproduction type,"
      "underexcretion type," and "combined type" based on only renal urate excretion,
      without considering an extra-renal pathway such as gut excretion. In this study,
      we investigated the effects of ABCG2 dysfunction on human urate handling and the
      mechanism of hyperuricemia. Clinical parameters for urate handling including
      urinary urate excretion (UUE) were examined in 644 Japanese male outpatients with
      hyperuricemia. The severity of their ABCG2 dysfunction was estimated by genotype
      combination of two common ABCG2 variants, nonfunctional Q126X (rs72552713) and
      half-functional Q141K (rs2231142). Contrary to the general understanding that
      ABCG2 dysfunction leads to decreased renal urate excretion, UUE was significantly
      increased by ABCG2 dysfunction (P=3.60*10(-10)). Mild, moderate, and severe ABCG2
      dysfunctions significantly raised the risk of "overproduction" hyperuricemia
      including overproduction type and combined type, conferring risk ratios of 1.36,
      1.66, and 2.35, respectively. The present results suggest that common
      dysfunctional variants of ABCG2 decrease extra-renal urate excretion including
      gut excretion and cause hyperuricemia. Thus, "overproduction type" in the current
      concept of hyperuricemia should be renamed "renal overload type," which is caused
      by two different mechanisms, "extra-renal urate underexcretion" and genuine
      "urate overproduction." Our new concept will lead to a more accurate diagnosis
      and more effective therapeutic strategy for hyperuricemia and gout.

PMID- 24940679
TI  - ABCG2 dysfunction increases serum uric acid by decreased intestinal urate
      excretion.
AB  - ATP-binding cassette transporter G2 (ABCG2), also known as breast cancer
      resistance protein (BCRP), is identified as a high-capacity urate exporter and
      its dysfunction has an association with serum uric acid (SUA) levels and
      gout/hyperuricemia risk. However, pathophysiologically important pathway(s)
      responsible for the ABCG2-mediated urate excretion were unknown. In this study,
      we investigated how ABCG2 dysfunction affected the urate excretion pathways.
      First, we revealed that mouse Abcg2 mediates urate transport using the membrane
      vesicle system. The export process by mouse Abcg2 was ATP-dependent and not
      saturable under the physiological concentration of urate. Then, we characterized
      the excretion of urate into urine, bile, and intestinal lumen using in vivo mouse
      model. SUA of Abcg2-knockout mice was significantly higher than that of control
      mice. Under this condition, the renal urate excretion was increased in Abcg2
      knockout mice, whereas the urate excretion from the intestine was decreased to
      less than a half. Biliary urate excretion showed no significant difference
      regardless of Abcg2 genotype. From these results, we estimated the relative
      contribution of each pathway to total urate excretion; in wild-type mice, the
      renal excretion pathway contributes approximately two-thirds, the intestinal
      excretion pathway contributes one-third of the total urate excretion, and the
      urate excretion into bile is minor. Decreased intestinal excretion could account
      for the increased SUA of Abcg2-knockout mice. Thus, ABCG2 is suggested to have an
      important role in extra-renal urate excretion, especially in intestinal
      excretion. Accordingly, increased SUA in patients with ABCG2 dysfunction could be
      explained by the decreased excretion of urate from the intestine. 

PMID- 24940680
TI  - Mitochondrial thymidine kinase 2 but not deoxyguanosine kinase is up-regulated
      during the stationary growth phase of cultured cells.
AB  - Mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) catalyze
      the initial phosphorylation of pyrimidine and purine deoxyribonucleosides, and
      are essential for maintaining mitochondrial dNTP pools for mitochondrial DNA
      replication. Here the expression of mitochondrial TK2 and dGK in relation to cell
      growth phases in cultured cells was investigated. TK2 and dGK protein levels in
      isolated mitochondria and TK2 activity in total cell extracts from U2OS and TK1
      deficient L929 cells were determined. We found that TK2 levels were negatively
      correlated with cell growth rates and there was an exponential increase in TK2
      levels in cells entering stationary phase. The expression of dGK did not change
      and appeared to be constitutive. 

PMID- 24940681
TI  - Tomato thymidine kinase is subject to inefficient TTP feedback regulation.
AB  - A promising suicide gene therapy system to treat gliomas has been reported: the
      thymidine kinase 1 from tomato (toTK1) combined with the nucleoside analog pro
      drug zidovudine (azidothymidine, AZT), which is known to penetrate the blood
      brain barrier. Transduction with toTK1 has been found to efficiently increase the
      sensitivity of human glioblastoma cells to AZT, and nude rats with intracranial
      glioblastoma grafts have shown significantly improved survival when treated with
      the toTK1/AZT system. We show in our paper that the strong suicidal effect of AZT
      together with toTK1 may be explained by reduced TTP-mediated feedback inhibition
      of the AZT phosphorylation. 

PMID- 24940682
TI  - Plants salvage deoxyribonucleosides in mitochondria.
AB  - Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides into the
      corresponding 5'-monophosphate deoxyribonucleosides to supply the cell with
      nucleic acid precursors. In mitochondrial fractions of the model plant
      Arabidopsis thaliana, we detected deoxyadenosine and thymidine kinase activities,
      while the cytosol fraction contained six-fold lower activity and chloroplasts
      contained no measurable activities. In addition, a mitochondrial fraction
      isolated from the potato Solanum tuberosum contained thymidine kinase and
      deoxyadenosine kinase activities. We conclude that an active salvage of
      deoxyribonucleosides in plants takes place in their mitochondria. In general, the
      observed localization of the plant dNK activities in the mitochondrion suggests
      that plants have a different organization of the deoxyribonucleoside salvage
      compared to mammals. 

PMID- 24940683
TI  - Mycoplasma pneumoniae thymidine phosphorylase.
AB  - Mycoplasma pneumoniae (Mpn) is a human pathogen causing acute respiratory
      diseases and accounts for approximately 30% cases of community-acquired
      pneumonia. Co-infection with Mycoplasmas compromises the efficacy of anticancer
      and antiviral nucleoside analog-based drugs due to the presence of Mycoplasma
      thymidine phosphorylase (TP). In this study, a TP-deficient strain of Mpn was
      generated in order to study the effect of Mpn TP in the metabolism of nucleoside
      analogs. Deficiency in TP activity led to increased uptake and incorporation of
      radiolabeled deoxyuridine and uracil but thymidine uptake was not affected. The
      activities of enzymes in the salvage of thymidine and deoxyuridine, e.g.,
      thymidine kinase and uracil phosphoribosyltransferase were upregulated in the TP
      deficient mutant, which may explain the increased uptake of deoxyuridine and
      uracil. Thirty FDA-approved anticancer and antiviral nucleoside and nucleobase
      analogs were used to screen their inhibitory activity toward the TP mutant and
      the wild type strain. Seven analogs were found to inhibit strongly the growth of
      both wild type and TP mutant. Differences in the inhibitory effect of several
      purine analogs between the two strains were observed. Further study is needed in
      order to understand the mechanism of inhibition caused by these analogs. Our
      results indicated that TP is not an essential gene for Mpn survival and TP
      deficiency affects other enzymes in Mpn nucleotide metabolism, and suggested that
      Mycoplasma nucleotide biosynthesis pathway enzymes are potential targets for
      future development of antibiotics. 

PMID- 24940684
TI  - Immunohistochemical and functional analysis of ectonucleoside triphosphate
      diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73) in pig aortic valves.
AB  - Extracellular nucleotides control mechanisms such as thrombosis or inflammation
      that are important in several pathologies, including heart valve disease and
      calcification. Ectonucleoside triphosphate diphosphohydrolase 1 (eNTPD1, CD39)
      and ecto-5'-nucleotidase (e5NT, CD73) are ectoenzymes that convert adenosine
      triphosphate to adenosine diphosphate, adenosine monophosphate and finally to
      adenosine. Changes in activities of these enzymes influence extracellular
      nucleotide concentrations and therefore could be involved in valve pathology.
      This study aimed to analyze type of cells, specific area, level of expression and
      biochemical function of CD39 and CD73 in pig aortic valves. Samples were
      collected from aortic valves of domestic pigs. Histological sections were cut
      from paraffin embedded tissue blocks. Following incubation with primary antibody
      against CD39 or CD73, washing and secondary goat anti-rabbit secondary
      antibodies, slides were viewed with NanoZoomer scanner. Substantial expression
      CD39 and CD73 was observed in two main types of valve cells: endothelial and
      valve interstitial cells. Subsequently, biochemical function of CD39 and CD73 was
      evaluated in cells cultured from pig aortic valve. Breakdown of extracellular
      nucleotides added to cell medium was analyzed with high performance liquid
      chromatography. In the interstitial cells, the CD73 products formation was much
      faster than in endothelium, while for the CD39 activity this relation was
      opposite. Expression and high concentration of CD39 and CD73 products in
      endothelium are expected, but presence of CD73 in valve interstitial cells is a
      surprise. We conclude that CD39 and CD73 and their enzymatic activities that
      convert extracellular nucleotides are highly expressed and could have special
      function in the valve. 

PMID- 24940685
TI  - Functional analysis of expression of human ecto-nucleoside triphosphate
      diphosphohydrolase-1 and/or ecto-5'-nucleotidase in pig endothelial cells.
AB  - Adenine nucleosides and nucleotides are important signaling molecules involved in
      control of key mechanisms of xenotransplant rejection. Extracellular pathway that
      converts ATP and ADP to AMP, and AMP to adenosine mainly mediated by ecto
      nucleoside triphosphate diphosphohydrolase 1, (ENTPD1 or CD39) and ecto-5'
      nucleotidase (E5NT or CD73) respectively, is considered as important target for
      xenograft protection. To clarify feasibility of combined expression of human
      ENTPD1 and E5NT and to study its functional effect we transfected pig endothelial
      cell line (PIEC) with both genes together. To do this we have produced a
      dicistronic construct bearing F2A sequence in frame between human E5NT and human
      ENTPD1 coding sequences. PIEC cells were mock-transfected as transfection control
      or transfected with plasmids encoding human ENTPD1 or human E5NT. PIEC cells were
      exposed to 50 MUM ATP or 50 MUM ADP or 50 MUM AMP. Conversion of extracellular
      substrates into products (ATP/ADP/AMP/adenosine) was measured by HPLC in the
      media collected at specific time intervals. Following addition of AMP, production
      of adenosine in the medium of E5NT/ENTPD1- and E5NT- transfected cells increased
      to 14.2+/-1.1 and 24.5+/-3.4 MUM respectively while it remained below 1 MUM in
      controls and in ENTPD1-transfected cells. A marked increase of adenosine
      formation from ADP or ATP was observed only in E5NT/ENTPD1-transfected cells
      (11.7+/-0.1 and 5.7+/-2.2 MUM respectively) but not in any other condition
      studied. This study indicates feasibility and functionality of combined
      expression of human E5NT and ENTPD1 in pig endothelial cells using F2A sequence
      bearing construct.

PMID- 24940686
TI  - Effect of AMP-deaminase 3 knock-out in mice on enzyme activity in heart and other
      organs.
AB  - Recent findings suggest that inhibition of AMP-deaminase (AMPD) could be
      effective therapeutic strategy in heart disease associated with cardiac ischemia.
      To establish experimental model to study protective mechanisms of AMPD inhibition
      we developed conditional, cardiac specific knock-outs in Cre recombinase system.
      AMPD3 floxed mice were crossed with Mer-Cre-Mer mice. Tamoxifen was injected to
      induce Cre recombinase. After two weeks, hearts, skeletal muscle, liver, kidney,
      and blood were collected and activities of AMPD and related enzymes were analyzed
      using HPLC-based procedure. We demonstrate loss of more than 90% of cardiac AMPD
      activity in the heart of AMPD3-/-mice while other enzymes of nucleotide
      metabolism such as adenosine deaminase, purine nucleoside phosphorylase were not
      affected. Surprisingly, activity of AMPD was also reduced in the erythrocytes and
      in the kidney by 20%-30%. No change of AMPD activity was observed in the skeletal
      muscle and the liver.

PMID- 24940687
TI  - Extracellular nucleotide catabolism in aortoiliac bifurcation of atherosclerotic
      ApoE/LDLr double knock out mice.
AB  - Atherosclerosis is a consequence of diverse pathologies that could be affected by
      signaling mediated by nucleotides and their metabolites. Concentration of
      specific nucleotide derivatives in the proximity of purinergic receptors is
      controlled by extracellular enzymes such as ecto-nucleoside triphopsphate
      diphosphohydrolase (eNTPD), ecto-5'-nucleotidase (e5NT), and ecto-adenosine
      deaminase (eADA). To estimate changes in metabolism of extracellular nucleotides
      in the atherosclerotic vessel wall, aortoiliac bifurcation of ApoE/LDLr (-/-)
      mice was perfused with solution containing adenosine-5'-triphosphate (ATP),
      adenosine-5'-monophosphate (AMP) or adenosine. Formation of the product of eNTPD,
      e5NT or eADA was measured by high performance liquid chromatography (HPLC). The
      most significant difference between ApoE/LDLr (-/-) and wild-type mice was
      several times higher rate of conversion of adenosine to inosine catalyzed by eADA
      activity. This highlights potential decrease in intravascular adenosine
      concentration in atherosclerosis. 

PMID- 24940688
TI  - Extracellular adenine nucleotide catabolism in heart valves.
AB  - Enzymes of extracellular nucleotide catabolism, such as ecto-nucleoside
      triphosphate diphosphohydrolase (eNTPD), ecto-5'-nucleotidase (e5NT) and ecto
      adenosine deaminase (eADA), control extracellular concentrations of adenine
      nucleotides and adenosine, furthermore in that way regulate inflammation, immune
      response, and platelets aggregation. In valves, disturbances of these processes
      may lead to their dysfunction and calcification. The aim of this study was to
      analyze the distribution of enzymes, which are engaged in extracellular
      nucleotide metabolism on the surface of pig aortic and pulmonary valves in
      relation to activities in the vessel wall. Activity of e5NT was two times higher
      on the surface of the aortic valve in comparison to the aorta. The same relation
      between activity of this enzyme in the pulmonary valve and pulmonary artery can
      be observed. In contrast, eADA activity on the valve surface is much lower than
      in the vessel wall. No significant differences were observed between the activity
      of eNTPD on the valve and the vessel surface. This highlights that pattern of
      enzymes activities favors the production and retention of adenosine on the valve
      surface and that its alterations could play a role in valve pathology. 

PMID- 24940689
TI  - Effect of 4-pyridone-3-carboxamide ribonucleoside (4PYR)-potential cardiovascular
      toxin in perfused rat heart.
AB  - We recently described a new nicotinamide derivative: 4-pyridone-3-carboxamide
      ribonucleoside (4PYR) and its conversion to intracellular metabolites (4PYR
      monophosphate: 4PYMP and 4PYR adenylate diphosphate: 4PYRAD). The aim of this
      study was to clarify the metabolism and physiological effects of brief exposure
      to 4PYR in perfused rat heart. Rat hearts were perfused in Langendorff mode.
      After 15 min equilibration, 100 MUM 4PYR (or solvent in controls) was infused
      into coronary circulation for 5 min. Coronary flow was recorded with
      electromagnetic flow meter and left ventricular mechanical function was assessed
      with intraventricular baloon by constructing pressure-volume relations. After
      perfusion hearts were freeze-clamped and analyzed using HPLC for phosphocreatine,
      creatine, ATP with metabolites as well as 4PYR metabolites. 4PYR infused into the
      coronary circulation was rapidly converted in the heart into 4PYMP and 4PYRAD
      with concentrations reaching 85.6+/-46.9 and 43.9+/-6.4 nmol/g dry weight,
      respectively, while control concentrations were below 20 nmol/g. 4PYR had no
      effect on baseline coronary flow (11.9+/-2.3 ml/min versus 11.0+/-2.7 ml/min in
      control) or stimulated by shear stress (23.2+/-4.5 ml/min versus 23.1+/-5.2
      ml/min in control). Both systolic and diastolic left ventricular mechanical
      function were not affected by 4PYR. No difference was noted for heart rate.
      Myocardial concentrations of ATP or phosphocreatine were also not affected by
      4PYR. We conclude that 4PYR has no immediate effect on coronary endothelium or
      cardiomyocyte functions such as coronary flow, rhythm, diastolic properties, or
      contractility despite rapid incorporation into intracellular metabolites. This
      study also indicates the lack of effect on purinergic receptors.

PMID- 24940690
TI  - 4-Pyridone-3-carboxamide-1beta-D-ribonucleoside metabolism in endothelial cells
      and its impact on cellular energetic balance.
AB  - 4-Pyridone-3-carboxamide-1beta-D-ribonucleoside (4PYR) is a naturally occurring
      compound related to nicotinamide that could be metabolized to mono-, di-, and
      triphosphates of 4PYR (4PYMP, 4PYDP, 4PYTP) and nicotinamide adenine dinucleotide
      (NAD) analogue (4PYRAD) in all types of cells. Previous studies demonstrated that
      formation of 4PYMP and 4PYTP was dependent on adenosine kinase activity. Pathway
      of 4PYRAD production is not yet identified, but most likely this process involves
      production of 4PYMP. This study aimed to evaluate influence of 4PYR on metabolism
      of endothelial cells and to test effect of nucleoside transport inhibitors. 4PYR
      was obtained by chemical synthesis. Endothelial cell line (HMEC-1) was incubated
      for 24 or 48 hours with 100 MUM 4PYR. After incubation, cells were separated from
      medium and analyzed for concentrations of ATP, NAD, and 4PYR metabolites by using
      reversed-phase high performance liquid chromatography. We demonstrated
      progressive accumulation of 4PYR metabolites in endothelium that reached 33.2+/
      0.8 nmol/mg protein for 4PYMP and 5.25+/-0.17 nmol/mg protein for 4PYRAD after 48
      hour incubation with 4PYR. Dipyridamole protected from accumulation of 4PYR
      metabolites in endothelial cells. We conclude that endothelium is capable to
      convert 4PYR into intracellular metabolites and this causes disruption of cell
      energy balance. Nucleoside transport inhibition with dipyridamole could protect
      endothelium from this effect. This finding could be of clinical relevance in
      conditions associated with accumulation of 4PYR such as chronic renal disease.

PMID- 24940691
TI  - Effect of nitrosative stress on extracellular nucleotide metabolism in
      endothelial cells.
AB  - Mechanisms of free radical injury involve chemical modification of proteins,
      lipid derivatives and nucleic acids and consequent loss of its function. However,
      specific targets and exact sequence of events has not been fully clarified. We
      determined whether extracellular enzymes that are involved in adenosine formation
      such as ecto-5'nucleotidase (e5N) and removal such as extracellular form of
      adenosine deaminase (eADA) could be affected by peroxynitrite. We used intact
      cell assay system that involves exposure of cultured HMEC-1 cells to substrates
      followed by HPLC analysis of conversion of substrates into products. We found
      that e5N and ADA activities decreased by 20-40% after incubation for 20 or 60
      minutes with 30 MUM peroxynitrite. Decrease of cellular ATP and NAD was also
      observed. We conclude that besides other cytotoxic effects modification of
      extracellular enzymes of nucleotide metabolism could be important target for free
      radical injury. 

PMID- 24940692
TI  - Activity of AMP-regulated protein kinase and AMP-deaminase in the heart of mice
      fed high-fat diet.
AB  - AMP-regulated protein kinase (AMPK) is involved in numerous regulatory processes
      and its role in control of cardiac energy metabolism is particularly important.
      This activity could be affected by AMP-deaminase (AMPD) since substrate of AMPD
      is AMPK activator. Hearts of male mouse, fed for six weeks with normal or high
      fat diet, were fractionated to enrich AMPK activity. Purified fraction was
      incubated with AMARA peptide for up to 5 minutes and then conversion of AMARA to
      pAMARA was determined by liquid chromatography-mass spectrometry (LC/MS) using
      mass detector. Activity of AMPK in heart was 0.038+/-0.012 pmol/min/mg protein
      for mice fed high-fat diet and that was not different to control (0.032+/-0.01
      pmol/min/mg protein). We observed change in AMPD activity. It was 5.39+/-1.5
      nmol/mg tissue/min in heart of mice fed high-fat diet while in heart of mice fed
      low-fat diet it was 2.29+/-0.32 nmol/mg tissue/min. Data we present indicate that
      while total AMPK activity is not changed decrease in AMPD activity may affect
      AMPK signaling in diabetic heart.

PMID- 24940693
TI  - In vitro and cellular effects of 4-pyridone-3-carboxamide riboside on enzymes of
      nucleotide metabolism.
AB  - 4-Pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) is an endogenously
      produced nucleoside that has recently been identified as a substrate for
      intracellular phosphorylation to form nucleotide derivatives. Low level of 4PYR
      is normally present in human plasma, but 4PYR massively accumulates in patients
      with renal failure. This study aimed to evaluate effects of 4PYR and its
      monophosphate derivative (4PYMP) on several enzymes of nucleotide metabolism in
      homogenates and intact cells. Activities of adenosine monophosphate deaminase
      (AMPD), adenosine deaminase, ecto-5'-nucleotidase (e5NT), adenine
      phosphoribosyltransferase (APRT), hypoxanthine/guanine phosphoribosyltransferase,
      purine nucleoside phosphorylase, and S-adenosylhomocysteine hydrolase (SAHH) were
      evaluated in erythrocyte lysates, rat heart homogenates, and in the intact rat
      cardiomyocytes by high performance liquid chromatography-based assays. 4PYMP
      caused significant inhibition of AMPD in both erythrocyte lysate and heart
      homogenate with 50% inhibitory concentration (IC50) of 74 and 55 MUM,
      respectively. Inhibition of e5NT in heart homogenates was also noted with IC50 of
      63 MUM. 4PYMP slightly inhibited APRT and 4PYR caused moderate activation of
      SAHH. No effects on other enzymes studied were noted. Inhibition of AMPD by 4PYMP
      in homogenates was confirmed in the intact cell experiments with isolated
      cardiomyocytes that were allowed to accumulate 4PYMP by incubation with 4PYR. We
      conclude that among pathways studied, most important is the effect of 4PYMP on
      AMPD and that such effect could be one of the consequences of elevated plasma
      4PYR concentration. 

PMID- 24940694
TI  - Novel developments in the use of antimetabolites.
AB  - Antimetabolites are the most widely used and most efficacious group of anticancer
      drugs. Antimetabolites are also the oldest rationally designed anticancer drugs,
      targeted against RNA and DNA, and can, therefore, be considered as the first
      generation of targeted drugs. Unfortunately, resistance often develops, leading
      to the design of new antimetabolites, which either have a novel mechanism of
      action, bypass resistance or in combination enhance the effect of other drugs,
      such as another antimetabolite, other DNA, or protein kinase targeted anticancer
      drugs. Several novel antimetabolites are in clinical development. The cytidine
      analog fluorocyclopentenylcytosine (RX-3117) is active in gemcitabine-resistant
      tumors and is activated by uridine-cytidine-kinase, can be incorporated into RNA
      and DNA and can downregulate DNA-methyltransferase-1. TAS-114 is a new generation
      dUTPase inhibitor. dUTPase normally prevents incorporation of dUTP and of the 5FU
      nucleotide FdUTP into DNA. However, inhibition of dUTPase will enhance their
      incorporation, thereby increasing thymine-less cell-death. The formulation TAS
      102 (trifluorothymidine and thymidine-phosphorylase-inhibitor) acts by
      incorporation into DNA and has shown efficacy in tumors progressing on 5FU
      therapy. Gemcitabine and cytarabine prodrugs were tested in model systems and
      have entered clinical evaluation. The elaidic-acid prodrugs of gemcitabine (CP
      4126, CO101) and cytarabine (elacytarabine) failed in randomized Phase III
      studies. Two other gemcitabine prodrugs LY2334737 (gemcitabine with a valproic
      acid at the 5'-position) and NUC1031 (a 5'-arylphosphoamidate prodrug, with a
      side-chain at the 5'-phosphate) are in early clinical development. In summary,
      several novel antimetabolites show promise in clinical development, either
      because of a novel mechanism of action, or clever combination or by innovative
      prodrug design. 

PMID- 24940695
TI  - Mechanisms of action of fludarabine nucleoside against human Raji lymphoma cells.
AB  - Fludarabine (2-FaraAMP) is a purine analog that is effective against chronic
      lymphocytic leukemia (CLL) and non-Hodgkins lymphoma (NHL). For some cases of
      CLL, 2-FaraAMP as a single agent can clear the blood of leukemia cells, but
      leukemia stem cells usually remain protected in sanctuary sites. It is clear that
      2-FaraAMP has multiple mechanisms of action that may collectively result in
      strand breaks in DNA, accumulation of phosphorylated p53 and apoptosis. We have
      demonstrated using the human Burkitt's lymphoma B-cell line, Raji, that p53, p63
      and p73 all accumulate in the nucleus, following treatment of cells with
      fludarabine nucleoside (2-FaraA). In addition, phosphorylated p53 accumulates in
      the cytosol and at mitochondria. Using sophisticated methods of proteomic
      analysis with mass spectrometry, proteins that become differentially abundant
      after treatment of cells with 2-FaraA have been identified, providing
      considerable additional information about the cellular responses of B-lymphoid
      cancers to this purine analog. The levels of proteins involved in the unfolded
      protein response increase, indicating that endoplasmic reticulum stress is likely
      to be one mechanism for induction of apoptosis. The levels of a number of
      proteins found on the outer plasma membrane change on cells treated with 2-FaraA,
      suggesting that signaling from the B-cell antigen receptor (BCR) is stimulated,
      resulting in induction of apoptosis through the intrinsic pathway. Increased
      levels of the cell surface proteins, CD50, CD100 and ECE-1, would promote
      survival of these cells; the balance between these survival and death responses
      would determine the fate of the cell. 

PMID- 24940696
TI  - miR-211 modulates gemcitabine activity through downregulation of ribonucleotide
      reductase and inhibits the invasive behavior of pancreatic cancer cells.
AB  - Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC)
      patients benefit from gemcitabine-based chemotherapy, thus the identification of
      novel prognostic factors is essential. In a high-throughput, microRNA (miRNA)
      array, miR-211 emerged as the best discriminating miRNA, with high expression
      associated with long survival. Here, we further explored the biological role of
      miRNA-211 in gemcitabine activity in the human PDAC cells (SUIT-2) subclones
      SUIT2-007 and SUIT2-028. Our results showed that miR-211 was expressed
      differentially in PDAC cells characterized by differential metastatic capability.
      In particular, S2-028 with lower metastatic ability had a higher expression of
      miR-211, compared to the S2-007 with higher metastatic capacity. Enforced
      expression of miR-211 via pre-miR-211 significantly reduced cell migration and
      invasion (e.g., 40% reduction of invasion of SUIT2 cells, compared to control;
      p<.05). Moreover, we demonstrated that induction of the miR-211 expression in the
      cells increased the sensitivity to gemcitabine and reduced the expression of its
      target ribonucleotide reductase subunit 2 (RRM2). In conclusion, miR-211
      functional analyses suggested the role of RRM2 as a target of miR-211 in the
      modulation of gemcitabine sensitivity. Moreover, inhibition of cell migration and
      invasion might explain the less aggressive behavior of pancreatic cancer cells
      with higher expression levels of miR-211.

PMID- 24940697
TI  - The pyrimidine nucleoside phosphorylase of Mycoplasma hyorhinis and how it may
      affect nucleoside-based therapy.
AB  - Mycoplasmas are opportunistic parasites and some species are suggested to
      preferentially colonize tumor tissue in cancer patients. We could demonstrate
      that the annotated thymidine phosphorylase (TP) gene in the genome of Mycoplasma
      hyorhinis encodes a pyrimidine nucleoside phosphorylase (PyNPHyor) that not only
      efficiently catalyzes thymidine but also uridine phosphorolysis. The kinetic
      characteristics of PyNPHyor-catalyzed nucleoside and nucleoside analogue (NA)
      phosphorolysis were determined. We demonstrated that the expression of such an
      enzyme in mycoplasma-infected cell cultures dramatically alters the activity of
      various anticancer/antiviral NAs such as 5-halogenated pyrimidine nucleosides,
      including 5-trifluorothymidine (TFT). Due to their close association with human
      cancers, the presence of mycoplasmas may markedly influence the therapeutic
      efficiency of nucleoside-based drugs. 

PMID- 24940698
TI  - Selection of the best blood compartment to measure cytidine deaminase activity to
      stratify for optimal gemcitabine or cytarabine treatment.
AB  - Cytidine deaminase (CDA) plays a crucial role in the degradation of cytidine
      analogs, such as gemcitabine and cytarabine. Several studies showed that a low
      CDA activity is associated with more toxicity but a higher efficacy, while a high
      activity will lead to a lower efficacy but less toxicity. A stratified dosing
      strategy based on the relative CDA activity would increase efficiency. In order
      to predict these events, a reliable measurement of CDA with a validated method is
      crucial. We aimed to determine which phenotype assay would be most suitable; a
      spectrophotometric assay using cytidine as a substrate, or an HPLC assay using
      gemcitabine as a substrate. In serum and whole blood of 26 volunteers, both
      assays showed an excellent correlation (R>0.999), but not in plasma nor in red
      blood cells. Moreover, there was no difference between males and females. In
      conclusion, the spectrophotometric assay seems the most simple and cost-effective
      test. It should be performed in serum, while it should be normalized on protein
      content as measured by the Bicinchoninic Acid.

PMID- 24940699
TI  - Radiosensitization by thymidine phosphorylase inhibitor in thymidine
      phosphorylase negative and overexpressing bladder cancer cell lines.
AB  - TAS-102 (trifluorothymidine [TFT] and thymidine phosphorylase inhibitor [TPI] in
      a molar ratio of 1:0.5) has activity in 5-fluorouracil resistant colon cancer.
      TPI is added to increase TFT's bioavailability. TFT has a dual mechanism of
      action by inhibiting thymidylate synthase and by its incorporation into DNA.
      Interesting radiosensitizing effects of TPI were recently reported. The aim of
      our study was to determine whether TP expression would affect radiosensitivity
      and to characterize the effect of TPI. Two bladder cancer cell lines RT112 (TP
      negative) and RT112/TP (TP overexpression) were tested for drug sensitivity and
      radiosensitivity (clonogenic assay), with and without TFT and/or TPI. Expression
      of gamma H2AX was used as marker for DNA damage. RT112 cells were not more
      sensitive to TFT then RT112/TP cells. TPI alone did not inhibit cell growth of
      RT112 even at 100 MUM, but inhibited that of RT112/TP by 27%. In both RT112 and
      RT112/TP cells 10 MUM TPI did not or slightly affect radiosensitivity, but 100
      MUM TPI alone enhanced the radiation response (p<.05). TFT alone at 1 MUM and in
      combination with 10 MUM TPI did not affect the radiation response of both cell
      lines. TPI alone induced expression of UpsilonH2AX, which was increased in
      combination with radiation. In conclusion, TPI enhanced radiosensitivity at high
      concentrations, independent of TP expression, while TFT and TPI at a low
      concentration did not affect the radiosensitivity of RT112 and RT112/TP cell
      lines.

PMID- 24940700
TI  - Assessment of mercaptopurine (6MP) metabolites and 6MP metabolic key-enzymes in
      childhood acute lymphoblastic leukemia.
AB  - Pediatric acute lymphoblastic leukemia (ALL) is treated with combination
      chemotherapy including mercaptopurine (6MP) as an important component. Upon its
      uptake, 6MP undergoes a complex metabolism involving many enzymes and active
      products. The prognostic value of all the factors engaged in this pathway still
      remains unclear. This study attempted to determine which components of 6MP
      metabolism in leukemic blasts and red blood cells are important for 6MP's
      sensitivity and toxicity. In addition, changes in the enzymatic activities and
      metabolite levels during the treatment were analyzed. In a cohort (N=236) of
      pediatric ALL patients enrolled in the Dutch ALL-9 protocol, we studied the
      enzymes inosine-5'-monophosphate dehydrogenase (IMPDH), thiopurine S
      methyltransferase (TPMT), hypoxanthine guanine phosphoribosyl transferase
      (HGPRT), and purine nucleoside phosphorylase (PNP) as well as thioguanine
      nucleotides (TGN) and methylthioinosine nucleotides (meTINs). Activities of
      selected enzymes and levels of 6MP derivatives were measured at various time
      points during the course of therapy. The data obtained and the toxicity related
      parameters available for these patients were correlated with each other. We found
      several interesting relations, including high concentrations of two active forms
      of 6MP--TGN and meTIN--showing a trend toward association with better in vitro
      antileukemic effect of 6MP. High concentrations of TGN and elevated activity of
      HGPRT were found to be significantly associated with grade III/IV leucopenia.
      However, a lot of data of enzymatic activities and metabolite concentrations as
      well as clinical toxicity were missing, thereby limiting the number of assessed
      relations. Therefore, although a complex study of 6MP metabolism in ALL patients
      is feasible, it warrants more robust and strict data collection in order to be
      able to draw more reliable conclusions.

PMID- 24940701
TI  - Hyperuricemia in hematologic malignancies is caused by an insufficient urinary
      excretion.
AB  - In order to elucidate the mechanism of hyperuricemia in hematologic malignancies,
      we have retrospectively investigated the uric acid metabolism in 418 chemotherapy
      naive patients with hematologic malignancies. Hyperuricemia was present in 116
      (27.8%) of these patients on initial hospitalization. Among 65 hyperuricemic
      patients analyzed uric acid metabolism, six (9.2%) had overproduction type, 52
      (80.0%) had underexcretion type, and seven (10.8%) had a mixed type. Fourteen
      patients (3.3%) developed tumor lysis syndrome in 418 patients. 

PMID- 24940702
TI  - Determination and profiling of purines in foods by using HPLC and LC-MS.
AB  - Purines in food are known to raise serum uric acid levels. We determined the
      purine content of sweet potato and beef by high-performance liquid chromatography
      and liquid chromatography-mass spectrometry. The purine content of the samples
      was 118-1,034 MUmol/100 g. The total purine content was also divided into purine
      bases, nucleosides, nucleotides, and nucleic acids. Our results suggest that
      differences in total purine content and in the ratio of purine types between
      vegetables and beef cause a difference in elevation of serum uric acid levels. 

PMID- 24940703
TI  - Characterizing substrate properties of purine-related compounds with purine
      metabolism enzymes for enzymatic peak-shift HPLC method.
AB  - We have extended peak-shift method for measuring purine bases to make it suitable
      for other purine-related compounds. We optimized the reactions of the purine
      metabolism enzymes 5'-nucleotidase (EC 3.1.3.5), purine nucleoside phosphorylase
      (PNP) (EC 2.4.2.1), xanthine oxidase (XO) (EC 1.17.3.2), urate hydroxylase (EC
      1.7.3.3), adenosine deaminase (ADA) (EC 3.5.4.4), and guanine deaminase (EC
      3.5.4.3) by determining their substrate specificity and reaction kinetics. These
      enzymes eliminate the five purine base peaks (adenine, guanine, hypoxanthine,
      xanthine, and uric acid) and four nucleosides (adenosine, guanosine, inosine, and
      xanthosine). The bases and nucleosides can be identified and accurately
      quantified by comparing the chromatograms before and after treatment with the
      enzymes. Elimination of the individual purine compound peaks was complete in a
      few minutes. However, when there were multiple substrates, such as for XO, and
      when the metabolites were purine compounds, such as for PNP and ADA, it took
      longer to eliminate the peaks. The optimum reaction conditions for the peak-shift
      assay methods were an assay mixture containing the substrate (10 MUL, 0.1 mg/mL),
      the combined enzyme solution (10 MUL each, optimum concentration), and 50 mM
      sodium phosphate (up to 120 MUL, pH 7.4). The mixture was incubated for 60
      minutes at 37 degrees C. This method should be suitable for determining the
      purine content of a variety of samples, without interference from impurities. 

PMID- 24940704
TI  - Long-term follow up outcome results of Knifelight carpal tunnel release and
      conventional open release following a departmental randomized controlled trial. A
      prospective study.
AB  - BACKGROUND: Carpal tunnel syndrome is traditionally treated with open release
      through a long palmar incision, which leaves some patients with pillar pain and
      scar tenderness. The Knifelight (Stryker, Kalamazoo, MI) is an exciting new
      instrument that allows minimally invasive release of the transcarpal ligament
      without subjecting the patient to the traditional problematic open palmar
      incision. However, no long-term data has been published in the literature so far.
      MATERIAL AND METHODS: A modified QuickDASH score questionnaire was used to assess
      long-term results and patient satisfaction 10 years following our department's
      original randomized control trial comparing open carpal tunnel release (43
      patients) to carpal tunnel release using the Knifelight method (39 patients).
      RESULTS: The mean modified QuickDASH score was 33.71 (SD 23.27) for the open
      group and 13.22 (SD 13.62) for the Knifelight group (P-value=0.0024). Patients
      from the open group complained of pillar pain (30%), scar tenderness (25%) and
      recurrence of carpal tunnel symptoms (18%). Three patients had symptoms so severe
      that they could not perform their jobs. In the Knifelight group there were no
      reports of any pain, recurrence or scar-related problems and a high level of
      general satisfaction was observed with this group of patients. CONCLUSIONS: Our
      study results show that the minimally invasive Knifelight carpal tunnel release
      was associated with better clinical outcomes, less complications and overall
      better quality of life when compared to the conventional open carpal tunnel
      release.

PMID- 24940705
TI  - Comparative in vitro toxicity of nitrosamines and nitramines associated with
      amine-based carbon capture and storage.
AB  - Amine-based CO2 capture is a prime contender for the first full-scale
      implementation of CO2 capture at fossil fuel-fired power plants postcombustion.
      However, the formation of potentially carcinogenic N-nitrosamines and N
      nitramines from reactions of flue gas NOx with the amines presents a potential
      risk for contaminating airsheds and drinking water supplies. Setting regulatory
      emission limits is hampered by the dearth of toxicity information for the N
      nitramines. This study employed quantitative in vitro bioassays for mutagenicity
      in Salmonella typhimurium, and chronic cytotoxicity and acute genotoxicity in
      Chinese hamster ovary (CHO) cells to compare the toxicity of analogous N
      nitrosamines and N-nitramines relevant to CO2 capture. Although the rank order
      was similar for genotoxicity in CHO cells and mutagenicity in S. typhimurium, the
      Salmonella assay was far more sensitive. In general, mutagenicity was higher with
      S9 hepatic microsomal activation. The rank order of mutagenicity was N
      nitrosodimethylamine (NDMA)>N-nitrosomorpholine>N-nitrodimethylamine>1,4
      dinitrosopiperazine>N-nitromorpholine>1,4-dinitropiperazine>N
      nitromonoethanolamine>N-nitrosodiethanolamine>N-nitrodiethanolamine. 1
      Nitrosopiperazine and 1-nitropiperazine were not mutagenic. Overall, N
      nitrosamines were ~15-fold more mutagenic than their N-nitramine analogues.

PMID- 24940708
TI  - Polyethylenimine-assisted growth of high-aspect-ratio nitrogen-doped ZnO (NZO)
      nanorod arrays and their effect on performance of dye-sensitized solar cells.
AB  - The realization of arrays of high-aspect-ratio nitrogen-doped ZnO (NZO) nanorod
      is critical to the development of high-quality nanostructure-based optoelectronic
      and electronic devices. In this study, we used a solution-based method to grow
      arrays of vertically aligned high-aspect-ratio NZO nanorods on ZnO seed layer
      covered fluorine-doped tin oxide substrates. We investigated whether the
      diameters and aspect ratios of the nanorods were affected by the addition of
      polyethylenimine (PEI) to the precursor solution used as well as by variations in
      the growth temperature and the concentration of the precursor solution. The
      performances of dye-sensitized solar cells (DSSCs) in which the synthesized high
      aspect-ratio NZO nanorods were used as the photoanode material were also studied.
      That the dopant, nitrogen, was introduced into the ZnO lattice was confirmed
      using X-ray photoelectron spectroscopy and energy-dispersive X-ray spectroscopy.
      It was seen that after the addition of PEI, the NZO and ZnO nanorod arrays
      increased in length and their diameters became smaller (i.e., their aspect ratios
      increased). This resulted in an increase in the amount of dye absorbed by them,
      leading to improvements in the DSSCs based on the nanorods. The structural,
      morphological, optical, and photovoltaic characteristics of ZnO and NZO nanorod
      arrays synthesized using different precursor concentrations and growth
      temperatures (160-190  degrees C) were also examined. We also investigated the
      effect of the use of PEI on these characteristics. The power conversion
      efficiency (PCE) of DSSCs fabricated using the NZO nanorod arrays was found to be
      significantly higher than that of DSSCs based on the pure ZnO nanorod arrays.
      This increase in efficiency could be attributed to the combined effects of the
      increase in the charge-carrier concentration, change in morphology, and increase
      in the Fermi energy levels of the nanorods, which resulted because of N doping. A
      PCE of 5.0% was obtained for a DSSC based on a film of arrays of NZO nanorods
      having an aspect ratio of ~47 and synthesized using PEI. 

PMID- 24940706
TI  - Santiago Ramon y Cajal and three-dimensional cinema.
AB  - In this article, I present and comment on two unpublished letters written by the
      Spanish engineer Carlos Mendizabal Brunet to Santiago Ramon y Cajal informing him
      of the development of a new device for three-dimensional cinema and asking for
      his approval. Fortunately, the answers given by Cajal to these two letters have
      also been preserved, and they reveal his interest in three-dimensional cinema; in
      the letters, he reported that he himself had designed a prototype capable of
      creating on a screen a feeling of 3-D relief, a subject about which he was always
      passionate.

PMID- 24940709
TI  - [International health aid: shifting the balance toward health system
      strengthening].

PMID- 24940710
TI  - Correlation of neonatal weight with maternal serum levels of pregnancy-associated
      plasma protein-A during the first trimester of pregnancy: a retrospective study.
AB  - AIM: Evaluate the relationship between neonatal weight and pregnancy-associated
      plasma protein-A. METHODS: Retrospective study on 2564 singleton pregnancies with
      healthy term neonates in three groups of women with different values of pregnancy
      associated plasma protein-A who underwent the combined test during the first
      trimester. Non-parametric test and correlation analysis for statistical
      elaboration were carried out. RESULTS: There exists a correlation between the
      serum levels of pregnancy-associated plasma protein-A in the first trimester of
      pregnancy and neonatal weight. Values of pregnancy-associated plasma protein-A
      lower than the 25th percentile are associated with neonatal weight in a
      significant way. There was no significant association between pregnancy
      associated plasma protein-A values above 1.50 MoM and neonatal weight.
      CONCLUSION: This study confirms the positive correlation between circulating
      concentrations of pregnancy-associated plasma protein-A and fetal growth. Low
      neonatal weight and factors that can cause this could be determined from the
      first trimester by measuring the concentrations of pregnancy-associated plasma
      protein-A in maternal serum. Even if the association between the levels of
      pregnancy-associated plasma protein-A and a low neonatal weight has been
      demonstrated, however, we have to say that the sensitivity of a such screening
      method for the prediction of low birth weight and perinatal complications seems
      to be rather low. The variations of pregnancy-associated plasma protein-A during
      the first trimester cannot be used as a marker of excessive fetal growth.

PMID- 24940711
TI  - Performance of CKD-EPI equation to estimate glomerular filtration rate as
      compared to MDRD equation in South Brazilian individuals in each stage of renal
      function.
AB  - BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation seems to correct the overdiagnosis of chronic kidney disease (CKD)
      provided by Modification of Diet in Renal Disease (MDRD) equation. However, this
      point has not been tested in some ethnic groups. This study investigated the
      performance of MDRD and CKD-EPI equations in South Brazilian individuals.
      METHODS: This cross-sectional study included 354 individuals including healthy
      volunteers, diabetic and non-diabetic individuals with or without CKD. Glomerular
      filtration rate (GFR) was measured by the 51Cr-EDTA single-injection method (51Cr
      GFR). Accuracy (P30), bias, and Bland-Altman agreement plots were evaluated.
      RESULTS: In the group as a whole, 51Cr-GFR was 87+/-37 (6-187), CKD-EPI eGFR,
      82+/-30 (6-152), and MDRD eGFR, 77+/-28 (6-156) mL/min/1.73 m2 (p<0.001 for all
      comparisons). Analyzing the subset of individuals with 51Cr-GFR <60 mL/min/1.73
      m2, P30 values were, respectively, 76% and 84% for MDRD and for CKD-EPI (p<0.001)
      while for 51Cr-GFR >=60 mL/min/1.73 m2, P30 values were 57.5% for both equations
      (p=1.000). For MDRD and CKD-EPI, mean bias were negative for GFRs <60 (-11 vs. 
      12, p=0.221) and positive for values >60 (16 vs. 9, p<0.001). In multivariate
      analysis, absolute bias was unfavorably influenced by measured GFR >60 (for MDRD)
      and being diabetic or younger (for CKD-EPI). CONCLUSIONS: CKD-EPI reduces GFR
      underestimation in individuals with GFRs >60, but still presents a quite low
      accuracy at this GFR range. Moreover, it tends to overestimate GFR in subjects
      with GFRs <60 mL/min/1.73 m2. CKD stages 1 and 2, diabetes and young age had a
      negative influence on the performance of the equations.

PMID- 24940712
TI  - Galectin-3 in diabetic patients.
AB  - Galectin-3 is a versatile molecule which exerts several and sometimes opposite
      functions in various pathophysiological processes. Recently, galectin-3 has
      gained attention as a powerful predictor of heart failure and mortality, thus
      becoming a useful prognostic marker in clinical practice. Moreover, though not
      specifically investigated in diabetic cohorts, plasma levels of galectin-3
      correlated with the prevalence of diabetes and related metabolic conditions, thus
      suggesting that pharmacological blockade of this lectin might be successful for
      treating heart failure especially in subjects suffering from these disorders.
      Indeed, galectin-3 is considered not only as a marker of heart failure, but also
      as a mediator of the disease, due to its pro-fibrotic action, though evidence
      comes mainly from studies in galectin-3 deficient mice. However, these studies
      have provided contrasting results, with either attenuation or acceleration of
      organ fibrosis and inflammation, depending on the experimental setting and
      particularly on the levels of advanced glycation endproducts (AGEs)/advanced
      lipoxidation endproducts (ALEs), of which galectin-3 is a scavenging receptor. In
      fact, under conditions of increased AGE/ALE levels, galectin-3 ablation was
      associated with tissue-specific outcomes, reflecting the AGE/ALE-receptor
      function of this lectin. Conversely, in experimental models of acute inflammation
      and fibrosis, galectin-3 deficiency resulted in attenuation of tissue injury.
      There is a need for prospective studies in diabetic patients specifically
      investigating the relation of galectin-3 levels with complications and for
      further animal studies in order to establish the effective role of this lectin in
      organ damage before considering its pharmacological blockade in the clinical
      setting.

PMID- 24940713
TI  - Acute metformin intoxication: 2012 experience of Emergency Departement of Lodi,
      Italy.
AB  - Background: Metformin is a biguanide antihyperglycemic agent that decreases
      insulin resistance. It is removed through renal mechanisms and its clearance is
      reduced in renal failure. Metformin ingestion should always be considered in the
      differential diagnosis of any patient with metabolic acidosis and increased
      lactate level. Hemodialysis and continuous veno-venous hemofiltration (CVVH) are
      both efficient methods to treat metformin intoxication and correct metabolic
      abnormalities. METHODS: Patient 1: A 63-year-old man with type 2 diabetes
      mellitus presented to emergency department (ED) of Lodi (Italy) for dyspnea. He
      also reported having diarrhea for 10 days. Initial investigations revealed
      metabolic acidosis with hyperlactatemia and hypoglycemia (54 mg/dL), metformin
      concentration was 41 MUg/mL (normal value <4 MUg/mL). His hemodynamic condition
      became rapidly unstable and hypotension worsened despite CVVH being performed.
      Death occurred in 24 h. Patient 2: A 76-year-old man with type 2 diabetes
      mellitus presented to ED of Lodi for dyspnea. He referred a recent surgery
      amputation of the left foot's fifth phalanx for osteomyelitis, in levofloxacin
      therapy. Initial investigations revealed metabolic acidosis with hyperlactatemia
      and severe hypoglycemia (20 mg/dL). Two hemodialysis sessions were performed with
      complete normalization of the serum concentration of metformin. RESULTS AND
      CONCLUSIONS: In our two cases the genesis of metformin intoxication was clear,
      powered by acute renal failure, but less obvious was the etiology of acute renal
      damage responsible for metformin accumulation. Damage due to renal hypoperfusion
      or the direct toxic effect of metformin should be considered. Additionally, for
      the second patient, we can also hypothesize that interstitial nephritis was
      exacerbated by levofloxacin.

PMID- 24940714
TI  - Discrepant results in plasma, but not serum in the Beckman Coulter DxI Access
      HYPERsensitive hTSH 3rd generation assay affect the management of differentiated
      thyroid cancer and hyperthyroid patients.

PMID- 24940715
TI  - The impact of repeat-testing of common chemistry analytes at critical
      concentrations.
AB  - BACKGROUND: Early notification of critical values by the clinical laboratory to
      the treating physician is a requirement for accreditation and is essential for
      effective patient management. Many laboratories automatically repeat a critical
      value before reporting it to prevent possible misdiagnosis. Given today's
      advanced instrumentation and quality assurance practices, we questioned the
      validity of this approach. We performed an audit of repeat-testing in our
      laboratory to assess for significant differences between initial and repeated
      test results, estimate the delay caused by repeat-testing and to quantify the
      cost of repeating these assays. METHODS: A retrospective audit of repeat-tests
      for sodium, potassium, calcium and magnesium in the first quarter of 2013 at
      Tygerberg Academic Laboratory was conducted. Data on the initial and repeat-test
      values and the time that they were performed was extracted from our laboratory
      information system. The Clinical Laboratory Improvement Amendment criteria for
      allowable error were employed to assess for significant difference between
      results. RESULTS: A total of 2308 repeated tests were studied. There was no
      significant difference in 2291 (99.3%) of the samples. The average delay ranged
      from 35 min for magnesium to 42 min for sodium and calcium. At least 2.9% of
      laboratory running costs for the analytes was spent on repeating them.
      CONCLUSIONS: The practice of repeating a critical test result appears unnecessary
      as it yields similar results, delays notification to the treating clinician and
      increases laboratory running costs.

PMID- 24940716
TI  - The apolipoprotein B/apolipoprotein A-I ratio in healthy men with normolipidemia:
      limits of variation and relationship with other lipid parameters.

PMID- 24940718
TI  - Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in
      pathophysiology.
AB  - Arginine vasopressin (AVP) plays a key role in many physiologic and pathologic
      processes. The most important stimulus for AVP release is a change in plasma
      osmolality. AVP is also involved in the response and adaptation to stress.
      Reliable measurement of AVP is hindered by several factors. Over 90% of AVP is
      tightly bound to platelets, and its estimation is influenced by the number of
      platelets, incomplete removal of platelets or pre-analytical processing steps.
      Copeptin (CTproAVP), a 39-aminoacid glycopeptide, is a C-terminal part of the
      precursor pre-provasopressin (pre-proAVP). Activation of the AVP system
      stimulates CTproAVP secretion into the circulation from the posterior pituitary
      gland in equimolar amounts with AVP. Therefore CTproAVP directly reflects AVP
      concentration and can be used as a surrogate biomarker of AVP secretion. In many
      studies CTproAVP represents AVP levels and its behavior represents changes in
      plasma osmolality, stress and various disease states, and shows some of the
      various physiologic and pathophysiologic conditions associated with increased or
      decreased AVP. Increased CTproAVP concentration is described in several studies
      as a strong predictor of mortality in patients with chronic heart failure and
      acute heart failure. Autosomal polycystic kidney disease (ADPKD) patients have
      both central and nephrogenic defects in osmoregulation and CTproAVP balance. A
      possibility raised by these clinical observations is that CTproAVP may serve to
      identify patients who could benefit from an intervention aimed at countering AVP.

PMID- 24940717
TI  - Reference ranges for serum beta-trace protein in neonates and children younger
      than 1 year of age.
AB  - BACKGROUND: beta-Trace protein (BTP) has been proposed as an alternative
      endogenous marker of glomerular filtration rate. Data on BTP reference ranges in
      young children are scarce. We therefore aim to establish reference ranges and
      examine the developmental course of serum BTP in basically healthy children
      younger than 1 year of age. METHODS: Single blood samples were taken from healthy
      children (born at gestational age >=37 weeks) <12 months of age. Serum BTP was
      measured using the N latex B-trace protein assay (Siemens Diagnostics, Deerfield,
      IL, USA) on an Immage(r) 800 Rate Nephelometer (Beckman Coulter Inc. Brea, CA,
      USA). Serum creatinine and cystatin C were additionally determined and compared
      to reference values to confirm a normal renal function. RESULTS: From June 2010
      to January 2014, 95 blood samples were collected from 95 children {67.4% male;
      median age 120 days [inter quartile range 57-166]}. BTP was normally distributed
      (mean concentration 0.84+/-standard deviation 0.35 mg/L). Considering all
      children, the 50th centile BTP reference concentration was 0.82 mg/L (5th-95th
      centiles; 0.27-1.38). BTP concentrations were the highest in neonates and
      steadily declined with increasing age (Spearman's rank correlation was -0.415,
      p=0.002). No gender differences were found. CONCLUSIONS: Our data provide a BTP
      reference range for the first year of life. Seeing the biological pattern of BTP,
      with only a limited postnatal decline, this marker might offer a promising
      alternative to serum creatinine-based methods for estimating glomerular
      filtration rate in newborns.

PMID- 24940719
TI  - The protective effects of Ziziphus vulgaris L. fruits on biochemical and
      histological abnormalities induced by diabetes in rats.
AB  - BACKGROUND: Diabetes mellitus arises from a deficient production and action of
      insulin. Ziziphus vulgaris L. (jujube) is a medicinal plant that is known to have
      anti-diabetic actions. The aim of the present study was to investigate the
      protective effects of jujube fruit powder and extract against biochemical
      imbalances in streptozotocin (STZ)-induced diabetes. METHODS: Diabetes was
      induced in rats using intraperitoneal injection of STZ at a dose of 60 mg/kg body
      weight (bw). Jujube powder (1 g/kg bw) and extract (1 g/kg bw) were administered
      daily via gavage, from two weeks prior to three weeks after STZ injection. Serum
      concentrations of glucose, insulin, and lipids and histological changes of the
      pancreas tissue were assessed at the end of study. RESULTS: The kaempferol
      content of jujube extract was found to be 0.013 +/- 0.0005% (w/w). Two weeks of
      supplementation with jujube powder resulted in a significant reduction of serum
      glucose levels compared with the non-diabetic control group prior to STZ
      treatment. Both jujube preparations prevented serum insulin decrease following
      STZ treatment, increased antioxidant capacity, and reduced total cholesterol,
      high-density lipoprotein cholesterol, triglycerides, and malondialdehyde levels.
      Jujube powder reduced serum low-density lipoprotein cholesterol and C-reactive
      protein concentrations while jujube extract had no effect on these parameters.
      Histopathological examination revealed a significant attenuation of pancreatic
      inflammation in the jujube-treated animals. CONCLUSIONS: The present findings
      suggest a protective role of jujube supplementation, in particular in the
      powdered form, against diabetes-induced biochemical and histopathological
      abnormalities.

PMID- 24940720
TI  - Detection of histidine oxidation in a monoclonal immunoglobulin gamma (IgG) 1
      antibody.
AB  - Although oxidation of methionine and tryptophan are known as popular chemical
      modifications that occur in monoclonal antibody (mAb) molecules, oxidation of
      other amino acids in mAbs has not been reported to date. In this study, oxidation
      of the histidine residue in a human immunoglobulin gamma (IgG) 1 molecule was
      discovered for the first time by mass spectrometry. The oxidation of a specific
      histidine located at the CH2 domain of IgG1 occurred under light stress, but it
      was not observed under heat stress. With the forced degradation study using
      several reactive oxygen species, the singlet oxygen was attributed to a reactive
      source of the histidine oxidation. The reaction mechanism of the histidine
      oxidation was proposed on the basis of the mass spectrometric analysis of IgG1
      oxidized in deuterium oxide and hydrogen heavy oxide. 

PMID- 24940721
TI  - DFT study on the reaction mechanisms and stereoselectivities of NHC-catalyzed [2
      + 2] cycloaddition between arylalkylketenes and electron-deficient benzaldehydes.
AB  - In this paper, two possible mechanisms (mechanisms A and B) on the
      stereoselective [2 + 2] cycloaddition of aryl(alkyl)ketenes and electron
      deficient benzaldehydes catalyzed by N-heterocyclic carbenes (NHCs) have been
      investigated using density functional theory (DFT). Our calculated results
      indicate that the favorable mechanism (mechanism A) includes three processes: the
      first step is the nucleophilic attack on the arylalkylketene by the NHC catalyst
      to form an intermediate, the second step is the [2 + 2] cycloaddition of the
      intermediate and benzaldehyde for the formation of a beta-lactone, and the last
      step is the dissociation of the NHC catalyst and the beta-lactone. Notably, the
      [2 + 2] cycloaddition, in which two chiral centers associated with four
      configurations (SS, RR, SR and RS) are formed, is demonstrated to be both the
      rate- and stereoselectivity-determining step. Moreover, the reaction pathway
      associated with the SR configuration is the most favorable pathway and leads to
      the main product, which is in good agreement with the experimental results.
      Furthermore, the analysis of global and local reactivity indexes has been
      performed to explain the role of the NHC catalyst in the [2 + 2] cycloaddition
      reaction. Therefore, this study will be of great use for the rational design of
      more efficient catalysts for this kind of cycloaddition. 

PMID- 24940723
TI  - Editorial.

PMID- 24940724
TI  - Evaluation of traumatic events as defined by the DSM-IV-TR criteria.
AB  - Objective. We attempted to better evaluate clinicians' understanding of Criterion
      A1 of Posttraumatic Stress Disorder. Method. Approximately 50 mental health
      clinicians from the Department of Veterans Affairs evaluated 10 scenarios in
      which potentially traumatic events were described. Results. The results found
      psychiatrists and psychologists to be slightly more conservative in claiming an
      event was traumatic in comparison to social workers. In addition, events were
      deemed at a somewhat higher level of trauma for individuals who had less years of
      experience at the Department of Veterans Affairs. Conclusion. These data are
      presented as the initial step in better understanding the features included in
      determining whether an event is deemed traumatic according to the DSM-IV-TR
      criteria. 

PMID- 24940722
TI  - Reactant coordinate based state-to-state reactive scattering dynamics implemented
      on graphical processing units.
AB  - A parallel code for state-to-state quantum dynamics with propagation of time
      dependent wavepacket in reactant coordinates has been developed on graphical
      processing units (GPUs). The propagation of wavepacket and the transformation of
      wavepacket from reactant to product Jacobi coordinates are entirely calculated on
      GPUs. A new interpolation procedure is introduced for coordinate transformation
      to decrease the five-loop computation to two four-loop computations. This
      procedure has a negligible consumption of extra GPU memory in comparison with
      that of the wavepacket and produces a considerable acceleration of the
      computational speed of the transformation. The code is tested to get differential
      cross sections of H+HD reaction and state-resolved reaction probabilities of O+HD
      for total angular momenta J = 0, 10, 20, and 30. The average speedups are 57.0
      and 83.5 for the parallel computations on two C2070 and K20m GPUs relative to
      serial computation on Intel E5620 CPU, respectively. 

PMID- 24940725
TI  - Screening for depression in a diabetic outpatient population.
AB  - Depression occurs twice as often in patients with diabetes and is associated with
      reduced compliance with exercise, diet, and medications. It is also associated
      with hyperglycemia and increased diabetic complications. Despite evidence that
      successful treatment is associated with improved glycemic control, many cases of
      depression are left untreated. Objectives. (1) Evaluate a combination screening
      strategy in an outpatient population; and (2) explore the association between
      glycemic control and depressive symptomatology. Methods. Ninety-two patients
      completed the Patient Health Questionnaire (PHQ-2). Patients with a PHQ-2 score
      >= 1 completed the 16-item Quick Inventory of Depressive Symptomatology (QIDS
      SR16). Using the QIDS-SR16, a score of <=5 corresponded to normal mood, with
      scores above 5 corresponding to increasing severity of depressive symptoms.
      Glycemic control was assessed by glycosylated hemoglobin (HbA1c). Results. Using
      a PHQ-2 cut-off score of >=3, 37% of the sample screened positive for major
      depressive disorder (MDD), with an additional 27% reporting sub-threshold
      symptoms. The depressed group reported significantly more difficulty with reduced
      interests, insomnia, concentration, self-criticism, energy/fatigue and depressed
      mood. In terms of glycemic control, there was a marginally significant effect for
      race and HbA1c. Conclusion. The combined PHQ-2 and QIDS-SR16 can facilitate
      prompt detection of MDD and provide a means of monitoring specific symptoms and
      progress once treatment commences. 

PMID- 24940727
TI  - Pilot of group intervention for bipolar disorder.
AB  - Objective. This pilot study aimed to determine whether a group based psychosocial
      intervention reduced rates of relapse, improved function and quality of life in
      people with bipolar disorder. Method. Patients with a diagnosis of bipolar
      disorder, types I and II were recruited in the Geelong Region of Victoria.
      Patients were assessed at baseline for psychiatric status, mood episode,
      function, and medication adherence. They were randomly assigned to either the
      intervention arm, a 12-week, structured group-based therapy as an adjunct to
      treatment as usual or the control arm, which consisted of treatment as usual,
      plus weekly phone calls. Participants were then followed up for a period of 3
      months and assessed by a researcher blinded to treatment and control
      interventions. Results. Functioning as measured by the Global Assessment of
      Functioning (GAF) was significantly improved in the intervention group (P=0.008).
      The social relationships subscale on the (WHOQoL-BREF) showed significant results
      (P<0.05 level). There was also a positive trend in reduction of relapses in the
      intervention group. Conclusion. The use of a group intervention for bipolar
      disorder as an adjunct to usual treatment has potential benefits, both in
      reduction of relapse and improvement in functionality, and may be a cost
      effective way of delivering psychosocial treatments. 

PMID- 24940726
TI  - Risperidone in adolescent schizophrenic psychoses: A retrospective study.
AB  - Objective. The aim of the study was to assess the therapeutic effect and
      tolerability of risperidone in patients with early-onset schizophrenia and other
      related psychotic disorders. Methods. Our retrospective study included 47
      schizophrenic patients (27 boys, 20 girls) with an average age of 16.5+/-1.3
      years. The patients were evaluated based on their medical records prior to being
      started on risperidone, and then after 1, 3 and 6 weeks of risperidone
      administration. Efficacy of treatment was evaluated using the first item on the
      CGI scale. Survivors analysis was used. Results. After week 6, the average dose
      of risperidone was 3.8+/-1.4 mg. Eighty-two percent of the patients were
      evaluated as responders, 64% as full responders and 18% as partial responders.
      There were eight patients who dropped out of the study during treatment. The
      initial inclusion score on the CGI was 5.8+/-0.7. This score showed a steady
      decrease at each evaluation point during the treatment. At week 1 the score was
      4.5+/-1.1 (P<0.001), at week 3, 3.4+/-1.2 (P<0.001), and at week 6 it was 2.6+/
      1.2 (P<0.001). The medication was well tolerated. Less than half of the patients
      (46%) reported any side effects, according to their medical records. Parkinsonism
      (19%), sedation (8.5%) and hypersalivation (8.5%) were the most commonly reported
      side effects. The mean weight of the participants increased from 61.2+/-10.0 kg
      to 64.7+/-10.0 kg between baseline and week 6 (P=0.002). Conclusion. Our
      experience supports the use of risperidone in the treatment of schizophrenic
      disorders in adolescence. 

PMID- 24940728
TI  - Topiramate-induced psychotic exacerbation: case report and review of literature.
AB  - Background. Topiramate (TPM) is a new antiepileptic drug that is used mainly in
      the treatment of refractory partial epileptic seizures. There are some studies
      reporting TPM's effectiveness in the treatment and maintenance of some
      psychiatric illnesses such as acute mania, some other affective disorders, post
      traumatic stress disorder and binge-eating disorder. On the other hand, it has
      been shown that TPM may cause mild to moderate cognitive impairment and is
      thought to be responsible for a series of neuro-psychiatric signs and symptoms.
      Some of the available articles that have mentioned the relationship of psychotic
      symptoms and topiramate usage are discussed. Objective. The present paper aims to
      discuss a case of psychotic exacerbation purported to occur after TPM
      administration and to review specifically the literature on TPM's potential for
      inducing psychotic symptoms. The patient presented here is thought to be an
      undiagnosed schizophrenia patient until his admission to our clinic (Department
      of Psychiatry, Gazi University Medical School) with TPM-exacerbated psychotic
      symptoms. Conclusions. The current findings are still subject to controversy
      because of the presence of both individual case reports and case series on the
      association between appearance of psychotic symptoms and TPM usage. 

PMID- 24940729
TI  - Questionnaire on animal-assisted therapy (AAT): The expectation for AAT as a day
      care program for Japanese schizophrenic patients.
AB  - Animal-assisted therapy (AAT) was developed to promote human social and emotional
      functioning as a day-care program for psychiatric patients. In this study, we
      determined which animals 481 schizophrenic patients liked and what they thought
      about AAT, using an original questionnaire. It was found that more than 80% of
      the present patients liked animals and that they thought contact with animals was
      useful as a novel therapy. They had much interest in, and many hopes, for AAT. 

PMID- 24940731
TI  - Abstracts from the 7th international forum on mood and anxiety disorders.

PMID- 24940732
TI  - The morphology transformation from helical nanofiber to helical nanotube in a
      diarylethene self-assembly system.
AB  - A helical nanostructure can be obtained by self-assembly of a diarylethene
      derivative that bears two malononitrile substitutes in a tetrahydrofuran/water
      medium. It is revealed that the helical nanostructure changed from helical
      nanofiber to helical nanotube when the diarylethene monomer changed from the open
      ring isomer to the closed-ring isomer upon irradiation with 365 nm ultraviolet
      light, meanwhile, the helix angle of the nanostructure changed from 50 degrees 
      +/- 5 degrees  to 75 degrees  +/- 5 degrees . There is a great possibility that
      the helical nanofibers and helical nanotubes are assembled from dimers as base
      units based on theoretical calculation and experimental results. 

PMID- 24940733
TI  - Layered double hydroxide-based nanocarriers for drug delivery.
AB  - Biocompatible clay materials have attracted particular attention as the efficient
      drug delivery systems (DDS). In this article, we review developments in the use
      of layered double hydroxides (LDHs) for controlled drug release and delivery. We
      show how advances in the ability to synthesize intercalated structures have a
      significant influence on the development of new applications of these materials.
      We also show how modification and/or functionalization can lead to new
      biotechnological and biomedical applications. This review highlights the most
      recent progresses in research on LDH-based controlled drug delivery systems,
      focusing mainly on: (i) DDS with cardiovascular drugs as guests; (ii) DDS with
      anti-inflammatory drugs as guests; and (iii) DDS with anti-cancer drugs as
      guests. Finally, future prospects for LDH-based drug carriers are also discussed.

PMID- 24940734
TI  - Predicting case volume from the accumulating elective operating room schedule
      facilitates staffing improvements.
AB  - BACKGROUND: Precise estimates of final operating room demand can only be made 1
      or 2 days before the day of surgery, when it is harder to adjust staffing to
      match demand. The authors hypothesized that the accumulating elective schedule
      contains useful information for predicting final case demand sufficiently in
      advance to readily adjust staffing. METHODS: The accumulated number of cases
      booked was recorded daily, from which a usable dataset comprising 146 consecutive
      surgical days (October 10, 2011 to May 7, 2012, after removing weekends and
      holidays), and each with 30 prior calendar days of booking history, was
      extracted. Case volume prediction was developed by extrapolation from estimates
      of the fraction of total cases booked each of the 30 preceding days, and
      averaging these with linear regression models, one for each of the 30 preceding
      days. Predictions were verified by comparison with actual volume. RESULTS: The
      elective surgery schedule accumulated approximately three cases per day, settling
      at a mean +/- SD final daily volume of 117 +/- 12 cases. The model predicted
      final case counts within 8.27 cases as far in advance as 14 days before the day
      of surgery. In the last 7 days before the day of surgery, the model predicted the
      case count within seven cases 80% of the time. The model was replicated at
      another smaller hospital, with similar results. CONCLUSIONS: The developing
      elective schedule predicts final case volume weeks in advance. After
      implementation, overly high- or low-volume days are revealed in advance, allowing
      nursing, ancillary service, and anesthesia managers to proactively fine-tune
      staffing up or down to match demand.

PMID- 24940736
TI  - Cardiac high-energy phosphate metabolism alters with age as studied in 196
      healthy males with the help of 31-phosphorus 2-dimensional chemical shift
      imaging.
AB  - Recently published studies have elucidated alterations of mitochondrial oxidative
      metabolism during ageing. The intention of the present study was to evaluate the
      impact of ageing on cardiac high-energy phosphate metabolism and cardiac function
      in healthy humans. 31-phosphorus 2-dimensional chemical shift imaging (31P 2D
      CSI) and echocardiography were performed in 196 healthy male volunteers divided
      into groups of 20 to 40 years (I, n = 43), 40 to 60 years (II, n = 123) and >60
      years (III, n = 27) of age. Left ventricular PCr/beta-ATP ratio, myocardial mass
      (MM), ejection fraction and E/A ratio were assessed. Mean PCr/beta-ATP ratios
      were significantly different among the three groups of volunteers (I, 2.10 +/-
      0.37; II, 1.77 +/- 0.37; III, 1.45 +/- 0.28; all p<0.001). PCr/beta-ATP ratios
      were inversely related to age (r(2)  =  -0.25; p<0.001) with a decrease from 2.65
      by 0.02 per year of ageing. PCr/beta-ATP ratios further correlated with MM (r =  
      0.371; p<0.001) and E/A ratios (r = 0.213; p<0.02). Moreover, E/A ratios (r =  
      0.502, p<0.001), MM (r = 0.304, p<0.001), glucose-levels (r = 0.157, p<0.05) and
      systolic blood pressure (r = 0.224, p<0.005) showed significant correlations with
      age. The ejection fraction did not significantly differ between the groups. This
      study shows that cardiac PCr/beta-ATP ratios decrease moderately with age
      indicating an impairment of mitochondrial oxidative metabolism due to age.
      Furthermore, MM increases, and E/A ratio decreases with age. Both correlate with
      left-ventricular PCr/beta-ATP ratios. The findings of the present study confirm
      numerous experimental studies showing an impairment of cardiac mitochondrial
      function with age.

PMID- 24940735
TI  - Gene expression correlations in human cancer cell lines define molecular
      interaction networks for epithelial phenotype.
AB  - Using gene expression data to enhance our knowledge of control networks relevant
      to cancer biology and therapy is a challenging but urgent task. Based on the
      premise that genes that are expressed together in a variety of cell types are
      likely to functions together, we derived mutually correlated genes that function
      together in various processes in epithelial-like tumor cells. Expression
      correlated genes were derived from data for the NCI-60 human tumor cell lines, as
      well as data from the Broad Institute's CCLE cell lines. NCI-60 cell lines that
      selectively expressed a mutually correlated subset of tight junction genes served
      as a signature for epithelial-like cancer cells. Those signature cell lines
      served as a seed to derive other correlated genes, many of which had various
      other epithelial-related functions. Literature survey yielded molecular
      interaction and function information about those genes, from which molecular
      interaction maps were assembled. Many of the genes had epithelial functions
      unrelated to tight junctions, demonstrating that new function categories were
      elicited. The most highly correlated genes were implicated in the following
      epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3,
      MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1); interactions at
      adherens junctions (CDH1, ADAP1, CAMSAP3); interactions at desmosomes (PPL, PKP3,
      JUP); transcription regulation of cell-cell junction complexes (GRHL1 and 2);
      epithelial RNA splicing regulators (ESRP1 and 2); epithelial vesicle traffic
      (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B); epithelial Ca(+2) signaling (ATP2C2,
      S100A14, BSPRY); terminal differentiation of epithelial cells (OVOL1 and 2, ST14,
      PRSS8, SPINT1 and 2); maintenance of apico-basal polarity (RAB25, LLGL2, EPN3).
      The findings provide a foundation for future studies to elucidate the functions
      of regulatory networks specific to epithelial-like cancer cells and to probe for
      anti-cancer drug targets. 

PMID- 24940738
TI  - Compassion fade: affect and charity are greatest for a single child in need.
AB  - Charitable giving in 2013 exceeded $300 billion, but why do we respond to some
      life-saving causes while ignoring others? In our first two studies, we
      demonstrated that valuation of lives is associated with affective feelings (self
      reported and psychophysiological) and that a decline in compassion may begin with
      the second endangered life. In Study 3, this fading of compassion was reversed by
      describing multiple lives in a more unitary fashion. Study 4 extended our
      findings to loss-frame scenarios. Our capacity to feel sympathy for people in
      need appears limited, and this form of compassion fatigue can lead to apathy and
      inaction, consistent with what is seen repeatedly in response to many large-scale
      human and environmental catastrophes. 

PMID- 24940737
TI  - Contribution of a non-beta-cell source to beta-cell mass during pregnancy.
AB  - beta-cell mass in the pancreas increases significantly during pregnancy as an
      adaptation to maternal insulin resistance. Lineage tracing studies in rodents
      have presented conflicting evidence on the role of cell duplication in the
      formation of new beta-cells during gestation, while recent human data suggest
      that new islets are a major contributor to increased beta-cell mass in pregnancy.
      Here, we aim to: 1) determine whether a non-beta-cell source contributes to the
      appearance of new beta-cells during pregnancy and 2) investigate whether
      recapitulation of the embryonic developmental pathway involving high expression
      of neurogenin 3 (Ngn3) plays a role in the up-regulation of beta-cell mass during
      pregnancy. Using a mouse beta-cell lineage-tracing model, which labels insulin
      producing beta-cells with red fluorescent protein (RFP), we found that the
      percentage of labeled beta-cells dropped from 97% prior to pregnancy to 87% at
      mid-pregnancy. This suggests contribution of a non-beta-cell source to the
      increase in total beta-cell numbers during pregnancy. In addition, we observed a
      population of hormone-negative, Ngn3-positive cells in islets of both non
      pregnant and pregnant mice, and this population dropped from 12% of all islets
      cells in the non-pregnant mice to 5% by day 8 of pregnancy. Concomitantly, a
      decrease in expression of Ngn3 and changes in its upstream regulatory network
      (Sox9 and Hes-1) as well as downstream targets (NeuroD, Nkx2.2, Rfx6 and IA1)
      were also observed during pregnancy. Our results show that duplication of pre
      existing beta-cells is not the sole source of new beta-cells during pregnancy and
      that Ngn3 may be involved in this process. 

PMID- 24940739
TI  - An electrical analogy relating the Atlantic multidecadal oscillation to the
      Atlantic meridional overturning circulation.
AB  - The Atlantic meridional overturning circulation (AMOC) is the northward flow of
      surface water to subpolar latitudes where deepwater is formed, balanced by
      southward abyssal flow and upwelling in the vicinity of the Southern Ocean. It is
      generally accepted that AMOC flow oscillates with a period of 60-80 years,
      creating a regular variation in North Atlantic sea surface temperature known as
      the Atlantic multidecadal oscillation (AMO). This article attempts to answer two
      questions: how is the AMOC driven and why does it oscillate? Using methods
      commonly employed by chemical engineers for analyzing processes involving flowing
      liquids, apparently not previously applied to trying to understand the AMOC, an
      equation is developed for AMOC flow as a function of the meridional density
      gradient or the corresponding temperature gradient. The equation is based on the
      similarity between the AMOC and an industrial thermosyphon loop cooler, which
      circulates a heat transfer liquid without using a mechanical pump. Extending this
      equation with an analogy between the flow of heat and electricity explains why
      the AMOC flow oscillates and what determines its period. Calculated values for
      AMOC flow and AMO oscillation period are in good agreement with measured values. 

PMID- 24940740
TI  - Method for finding metabolic properties based on the general growth law. Liver
      examples. A general framework for biological modeling.
AB  - We propose a method for finding metabolic parameters of cells, organs and whole
      organisms, which is based on the earlier discovered general growth law. Based on
      the obtained results and analysis of available biological models, we propose a
      general framework for modeling biological phenomena and discuss how it can be
      used in Virtual Liver Network project. The foundational idea of the study is that
      growth of cells, organs, systems and whole organisms, besides biomolecular
      machinery, is influenced by biophysical mechanisms acting at different scale
      levels. In particular, the general growth law uniquely defines distribution of
      nutritional resources between maintenance needs and biomass synthesis at each
      phase of growth and at each scale level. We exemplify the approach considering
      metabolic properties of growing human and dog livers and liver transplants. A
      procedure for verification of obtained results has been introduced too. We found
      that two examined dogs have high metabolic rates consuming about 0.62 and 1 gram
      of nutrients per cubic centimeter of liver per day, and verified this using the
      proposed verification procedure. We also evaluated consumption rate of nutrients
      in human livers, determining it to be about 0.088 gram of nutrients per cubic
      centimeter of liver per day for males, and about 0.098 for females. This
      noticeable difference can be explained by evolutionary development, which
      required females to have greater liver processing capacity to support pregnancy.
      We also found how much nutrients go to biomass synthesis and maintenance at each
      phase of liver and liver transplant growth. Obtained results demonstrate that the
      proposed approach can be used for finding metabolic characteristics of cells,
      organs, and whole organisms, which can further serve as important inputs and
      constraints for many applications in biology (such as protein expression),
      biotechnology (synthesis of substances), and medicine. 

PMID- 24940742
TI  - A novel mouse model of ischemic carotid artery disease.
AB  - BACKGROUND: Carotid artery occlusive disease gradually develops over time,
      eventually leading to cerebral infarction and high mortality rate. Animal models
      replicating cerebral infarction resulting from carotid artery occlusive disease
      have thus been developed to test potential novel treatments, which could be
      subsequently administered clinically. METHODS: Adult C57BL/6J male mice were
      subjected to ameroid constrictor (AC) placement to gradually narrow the bilateral
      common carotid arteries. Cerebral blood flow (CBF) was measured at several time
      points. At 7 and 28 days post-operation, post-mortem brain samples were analyzed
      for ischemic changes. RESULTS: The mortality rate was 58.8% at 28 days post
      operation. Surviving mice with AC showed continuous reduction of CBF by up to 70%
      of the baseline level at 28 days. Most of the mice (75%) showed multiple cerebral
      infarctions in the gray and white matter. Non-surviving mice showed critical CBF
      reduction below 20-30% of the baseline level before death. CONCLUSION: The
      application of the AC on the bilateral common carotid arteries in mice could
      offer a reliable model of severe cerebrovascular insufficiency due to carotid
      artery occlusive disease and may thus be useful in exploring pharmacological
      intervention in stroke through monitoring survival rate, infarct formation, and
      CBF profile.

PMID- 24940741
TI  - A genome-wide association study on chronic HBV infection and its clinical
      progression in male Han-Taiwanese.
AB  - It is common to observe the clustering of chronic hepatitis B surface antigen
      (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus
      (HBV) could be the reason for the familial clustering of HBsAg carriers.
      Additionally, genetic and gender factors have been reported to be involved. We
      conducted a three-stage genome-wide association study to identify genetic factors
      associated with chronic HBV susceptibility. A total of 1,065 male controls and
      1,623 male HBsAg carriers were included. The whole-genome genotyping was done on
      Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips
      in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87*10(-14)), rs9276370
      (HLA-DQA2, P = 1.9*10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48*10(-11)
      and P = 6.66*10(-15) respectively) were significantly associated with persistent
      HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant
      association (P = 2.58*10(-10)). The "T-T-G-G-T" haplotype of the five SNPs
      further signified their association with the disease (P = 1.48*10(-12); OR =
      1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent
      in severe disease subgroups and associated with non-sustained therapeutic
      response (P = 0.0262). The "G-C" haplotype was associated with sustained
      therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA
      DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male
      Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated
      with clinical progression and therapeutic response.

PMID- 24940744
TI  - How do online social networks grow?
AB  - Online social networks such as Facebook, Twitter and Gowalla allow people to
      communicate and interact across borders. In past years online social networks
      have become increasingly important for studying the behavior of individuals,
      group formation, and the emergence of online societies. Here we focus on the
      characterization of the average growth of online social networks and try to
      understand which are possible processes behind seemingly long-range temporal
      correlated collective behavior. In agreement with recent findings, but in
      contrast to Gibrat's law of proportionate growth, we find scaling in the average
      growth rate and its standard deviation. In contrast, Renren and Twitter deviate,
      however, in certain important aspects significantly from those found in many
      social and economic systems. Whereas independent methods suggest no significance
      for temporally long-range correlated behavior for Renren and Twitter, a scaling
      analysis of the standard deviation does suggest long-range temporal correlated
      growth in Gowalla. However, we demonstrate that seemingly long-range temporal
      correlations in the growth of online social networks, such as in Gowalla, can be
      explained by a decomposition into temporally and spatially independent growth
      processes with a large variety of entry rates. Our analysis thus suggests that
      temporally or spatially correlated behavior does not play a major role in the
      growth of online social networks. 

PMID- 24940743
TI  - Expression of DISC1-interactome members correlates with cognitive phenotypes
      related to schizophrenia.
AB  - Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and
      functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a
      leading candidate gene for schizophrenia and related psychiatric conditions, in
      cognitive function. Altered expression of DISC1 and DISC1-interactors has been
      identified in schizophrenia. Dysregulated expression of DISC1-interactome genes
      might, therefore, contribute to schizophrenia susceptibility via disruption of
      molecular systems required for normal cognitive function. Here, the blood RNA
      expression levels of DISC1 and DISC1-interacting proteins were measured in 63
      control subjects. Cognitive function was assessed using neuropsychiatric tests
      and functional magnetic resonance imaging was used to assess the activity of
      prefrontal cortical regions during the N-back working memory task, which is
      abnormal in schizophrenia. Pairwise correlations between gene expression levels
      and the relationship between gene expression levels and cognitive function and N
      back-elicited brain activity were assessed. Finally, the expression levels of
      DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69
      schizophrenic subjects. We found that DISC1-interactome genes showed correlated
      expression in the blood of healthy individuals. The expression levels of several
      interactome members were correlated with cognitive performance and N-back
      elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed
      decreased expression in schizophrenic subjects compared to healthy controls. Our
      findings highlight the importance of the coordinated expression of DISC1
      interactome genes for normal cognitive function and suggest that dysregulated
      DISC1 and NDEL1 expression might, in part, contribute to susceptibility for
      schizophrenia via disruption of prefrontal cortex-dependent cognitive functions. 

PMID- 24940747
TI  - Simultaneous real-time 3D photoacoustic tomography and EEG for neurovascular
      coupling study in an animal model of epilepsy.
AB  - OBJECTIVE: Neurovascular coupling in epilepsy is poorly understood; its study
      requires simultaneous monitoring of hemodynamic changes and neural activity in
      the brain. APPROACH: Here for the first time we present a combined real-time 3D
      photoacoustic tomography (PAT) and electrophysiology/electroencephalography (EEG)
      system for the study of neurovascular coupling in epilepsy, whose ability was
      demonstrated with a pentylenetetrazol (PTZ) induced generalized seizure model in
      rats. Two groups of experiments were carried out with different wavelengths to
      detect the changes of oxy-hemoglobin (HbO2) and deoxy-hemoglobin (HbR) signals in
      the rat brain. We extracted the average PAT signals of the superior sagittal
      sinus (SSS), and compared them with the EEG signal. MAIN RESULTS: Results showed
      that the seizure process can be divided into three stages. A 'dip' lasting for 1
      2 min in the first stage and the following hyperfusion in the second stage were
      observed. The HbO2 signal and the HbR signal were generally negatively
      correlated. The change of blood flow was also estimated. All the acquired results
      here were in accordance with other published results. SIGNIFICANCE: Compared to
      other existing functional neuroimaging tools, the method proposed here enables
      reliable tracking of hemodynamic signal with both high spatial and high temporal
      resolution in 3D, so it is more suitable for neurovascular coupling study of
      epilepsy.

PMID- 24940748
TI  - Recent advances in polymeric electrospun nanofibers for drug delivery.
AB  - Electrospinning is a simple unit operation process by which polymeric nanofibers
      with diameters ranging from a few nanometers to hundreds of micrometers can be
      fabricated using an electrostatically operated jet of polymer solution or polymer
      melt. Nanofibers because of their interesting features, such as surface-to-volume
      ratio, high surface area, microporosity, and nonwoven structure, provide numerous
      opportunities to design novel carrier systems for large commodities of
      therapeutics. Physicochemical properties of nanofibers depend on several process
      and formulation parameters, such as applied voltage, flow rate, polymer
      selection, and concentration of polymer used. The applications of nanofibers in
      drug delivery are nearly unbounded. This review summarizes the most recent work
      done on the various physicochemical parameters of electrospinning and polymers
      used in making wide varieties of nanofibers along with their role in developing
      more effective, novel drug delivery systems. 

PMID- 24940746
TI  - GADD45a promoter regulation by a functional genetic variant associated with acute
      lung injury.
AB  - RATIONALE: Growth arrest DNA damage inducible alpha (GADD45a) is a stress-induced
      gene we have shown to participate in the pathophysiology of ventilator-induced
      lung injury (VILI) via regulation of mechanical stress-induced Akt ubiquitination
      and phosphorylation. The regulation of GADD45a expression by mechanical stress
      and its relationship with acute lung injury (ALI) susceptibility and severity,
      however, remains unknown. OBJECTIVES: We examined mechanical stress-dependent
      regulatory elements (MSRE) in the GADD45a promoter and the contribution of
      promoter polymorphisms in GADD45a expression and ALI susceptibility. METHODS AND
      RESULTS: Initial studies in GADD45a knockout and heterozygous mice confirmed the
      relationship of GADD45a gene dose to VILI severity. Human lung endothelial cells
      (EC) transfected with a luciferase vector containing the full length GADD45a
      promoter sequence (-771 to +223) demonstrated a >4 fold increase in GADD45a
      expression in response to 18% cyclic stretch (CS, 4 h) compared to static
      controls while specific promoter regions harboring CS-dependent MSRE were
      identified using vectors containing serial deletion constructs of the GADD45a
      promoter. In silico analyses of GADD45a promoter region (-371 to -133) revealed a
      potential binding site for specificity protein 1 (SP1), a finding supported by
      confirmed SP1 binding with the GADD45a promoter and by the significant
      attenuation of CS-dependent GADD45a promoter activity in response to SP1
      silencing. Separately, case-control association studies revealed a significant
      association of a GADD45a promoter SNP at -589 (rs581000, G>C) with reduced ALI
      susceptibility. Subsequently, we found allelic variation of this SNP is
      associated with both differential GADD45a expression in mechanically stressed EC
      (18% CS, 4 h) and differential binding site of interferon regulatory factor 7
      (IRF7) at this site. CONCLUSION: These results strongly support a functional role
      for GADD45a in ALI/VILI and identify a specific gene variant that confers risk
      for ALI.

PMID- 24940749
TI  - Novel strategies for effective transdermal drug delivery: a review.
AB  - Skin is the largest and easily accessible organ of the body and therefore can be
      extensively used as a prominent route of delivery for local and systemic effects.
      Though it presents a multifunctional barrier between body and surrounding
      particles, there are chances to deliver therapeutic nanocarrier, particularly in
      diseased skin. Both for dermal and transdermal drug delivery, the horny layer,
      i.e., the uppermost layer of the skin serve as the most resistant layer to be
      crossed and for this purpose, different perforation techniques are used that
      relatively widen the skin opening and allow the passage of drug (<= 10 mg) and
      micromolecules, but this amateur disruption of the skin can be avoided in order
      to preserve this barrier against cutaneous microbiota by using deformable
      nanocarriers. In this review, we discuss the nanosized aggregates and microneedle
      technology for the advanced delivery of vaccines, protein, peptides, nucleic
      acid, and hormone across the skin. 

PMID- 24940751
TI  - How reliable are ATP bioluminescence meters in assessing decontamination of
      environmental surfaces in healthcare settings?
AB  - BACKGROUND: Meters based on adenosine triphosphate (ATP) bioluminescence
      measurements in relative light units (RLU) are often used to rapidly assess the
      level of cleanliness of environmental surfaces in healthcare and other settings.
      Can such ATP measurements be adversely affected by factors such as soil and
      cleaner-disinfectant chemistry? OBJECTIVE: This study tested a number of leading
      ATP meters for their sensitivity, linearity of the measurements, correlation of
      the readings to the actual microbial contamination, and the potential
      disinfectant chemicals' interference in their readings. METHODS: First, solutions
      of pure ATP in various concentrations were used to construct a standard curve and
      determine linearity and sensitivity. Serial dilutions of a broth culture of
      Staphylococcus aureus, as a representative nosocomial pathogen, were then used to
      determine if a given meter's ATP readings correlated with the actual CFUs. Next,
      various types of disinfectant chemistries were tested for their potential to
      interfere with the standard ATP readings. RESULTS: All four ATP meters tested
      herein demonstrated acceptable linearity and repeatability in their readings.
      However, there were significant differences in their sensitivity to detect the
      levels of viable microorganisms on experimentally contaminated surfaces. Further,
      most disinfectant chemistries tested here quenched the ATP readings variably in
      different ATP meters evaluated. CONCLUSIONS: Apart from their limited sensitivity
      in detecting low levels of microbial contamination, the ATP meters tested were
      also prone to interference by different disinfectant chemistries.

PMID- 24940753
TI  - Cannabinoid receptor 2-63 QQ variant is associated with persistently normal
      aminotransferase serum levels in chronic hepatitis C.
AB  - BACKGROUND AND AIM: To evaluate in anti-HCV-positive patients the clinical impact
      of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q)
      of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R). PATIENTS AND
      METHODS: 253 consecutive anti-HCV-/HCV-RNA-positive patients were enrolled, of
      whom 53 were HCV carriers with persistently normal ALT (PNALT group) and 200 had
      a history of steadily abnormal serum ALT values (abnormal ALT group). All
      patients were naive for antiviral therapy and were screened for the CNR2
      rs35761398 polymorphism by a TaqMan assay. RESULTS: Subjects in the PNALT group,
      compared with those in the abnormal ALT group were older (58.5+/-12 vs. 50.7+/
      12.4 years, p = 0.001), more frequently female (66% vs. 42%, p = 0.003), with
      lower body mass index (BMI) (24.5+/-3.1 vs. 26.6+/-4.6, p = 0.003), and more
      frequently with HCV genotype 2 (43.1% vs 17.7%, p = 0.0002) and CB2-63 QQ variant
      (34% vs. 11%, p = 0.0001). Considering all 253 patients, no difference in the
      demographic, biochemical, or virological data was observed between patients in
      the different CB2-63 variants. The logistic regression analysis identified CB2-63
      QQ, HCV genotype 2, older age and lower BMI as independent predictors of PNALT
      (p<0.00001). DISCUSSION: The CB2-63 QQ variant in HCV patients was independently
      associated with the PNALT status.

PMID- 24940756
TI  - [Cornea and conjunctiva].

PMID- 24940755
TI  - Foldscope: origami-based paper microscope.
AB  - Here we describe an ultra-low-cost origami-based approach for large-scale
      manufacturing of microscopes, specifically demonstrating brightfield, darkfield,
      and fluorescence microscopes. Merging principles of optical design with origami
      enables high-volume fabrication of microscopes from 2D media. Flexure mechanisms
      created via folding enable a flat compact design. Structural loops in folded
      paper provide kinematic constraints as a means for passive self-alignment. This
      light, rugged instrument can survive harsh field conditions while providing a
      diversity of imaging capabilities, thus serving wide-ranging applications for
      cost-effective, portable microscopes in science and education. 

PMID- 24940754
TI  - Decellularized allogeneic heart valves demonstrate self-regeneration potential
      after a long-term preclinical evaluation.
AB  - Tissue-engineered heart valves are proposed as novel viable replacements granting
      longer durability and growth potential. However, they require extensive in vitro
      cell-conditioning in bioreactor before implantation. Here, the propensity of non
      preconditioned decellularized heart valves to spontaneous in body self
      regeneration was investigated in a large animal model. Decellularized porcine
      aortic valves were evaluated for right ventricular outflow tract (RVOT)
      reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow
      up months. Repositioned native valves (n = 2 for each time) were considered as
      control. Tissue and cell components from explanted valves were investigated by
      histology, immunohistochemistry, electron microscopy, and gene expression. Most
      substitutes constantly demonstrated in vivo adequate hemodynamic performances and
      ex vivo progressive repopulation during the 15 implantation months without signs
      of calcifications, fibrosis and/or thrombosis, as revealed by histological,
      immunohistochemical, ultrastructural, metabolic and transcriptomic profiles.
      Colonizing cells displayed native-like phenotypes and actively synthesized novel
      extracellular matrix elements, as collagen and elastin fibers. New mature blood
      vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves
      especially in the medial and adventitial tunicae of regenerated arterial walls.
      Such findings correlated to the up-regulated vascular gene transcription.
      Neoinnervation hallmarks were appreciated at histological and ultrastructural
      levels. Macrophage populations with reparative M2 phenotype were highly
      represented in repopulated valves. Indeed, no aspects of adverse/immune reaction
      were revealed in immunohistochemical and transcriptomic patterns. Among
      differentiated elements, several cells were identified expressing typical stem
      cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in
      significantly higher number and specific topographic distribution in respect to
      control valves. Following the longest follow-up ever realized in preclinical
      models, non-preconditioned decellularized allogeneic valves offer suitable
      microenvironment for in vivo cell homing and tissue remodeling. Manufactured with
      simple, timesaving and cost-effective procedures, these promising valve
      replacements hold promise to become an effective alternative, especially for
      pediatric patients. 

PMID- 24940757
TI  - [Topical chemotherapy for conjunctival tumours - the medical and legal bearings
      of the case].
AB  - The treatment management of malignant tumours is characterised and limited by
      specific features of the topographical structure of the eye. The anatomic
      characteristics of the conjunctival sac, the movable tissue structures and the
      need to take care of corneal transparency and conjunctival stability are the main
      concerns of the experts. Clinical studies have revealed adjuvant chemotherapy to
      have a positive effect as a therapeutic treatment for neoplasia of the
      conjunctiva and cornea. Although mitomycin and interferon are widely used, there
      are no phase III studies on local adjuvant chemotherapy (interferon, mitomycin, 5
      fluorouracil) that evaluate the proof of effectiveness, potential adverse effects
      or interactions with other drugs. For this reason, the currently available
      studies fail to comply with the jurisdiction of the German Federal Social Court.
      Hence, the Medical Service of the Health Insurance Funds (MDK) regionally does
      not accept the medical preconditions for reimbursement of the costs in adjuvant
      local chemotherapy. A doctor's unquestioned acceptance of such an MDK decision
      could have legal consequences. An off-label use is acceptable by law if there is
      no alternative treatment available with a higher evidence level that conforms to
      the medical standard. It is therefore recommendable for the Joint Federal
      Committee commissions the experts in ophthalmology and oncology on off-label use,
      to review the scientific evidence regarding adjuvant therapy of malignant tumours
      of the ocular surface. Only in this way can regional disparities in patient care,
      and intrusions on the doctor-patient relationship, be avoided. 

PMID- 24940758
TI  - [Factors influencing the measurement of tear film lipid layer thickness with
      interferometry].
AB  - INTRODUCTION: The quantitative measurement of the tear film lipid layer thickness
      is a relatively new and promising method. However, so far it has not been
      investigated whether there is a diurnal or a day to day variability and whether
      certain factors are confounding the measurement of the lipid layer thickness.
      MATERIALS AND METHODS: In three different experimental settings, 10 subjects
      without known sicca syndrome were examined at three different time points on one
      day, on three different days and before and after therapeutic expression of the
      Meibomian glands. As a comparison, the parameters tear film break-up time, tear
      meniscus height, diagnostic expression of the Meibomian glands and subjective
      symptoms, determined using the OSDI (ocular surface disease index) questionnaire,
      were measured. RESULTS: The results of the study showed a smaller variation of
      the lipid layer thickness measurements during the day and from day to day
      compared to the tear film break-up time. The expression of the Meibomian glands
      significantly increased the lipid layer thickness. There was a correlation
      between the baseline values of tear film break-up time and the lipid layer
      thickness. DISCUSSION: Our data showed that the lipid layer thickness as measured
      with the Lipiview(r) interferometer appears to be a relatively constant parameter
      over time. In addition, the expression of the Meibomian glands could be
      identified as a potential confounding factor. In this study we included only
      healthy subjects without known sicca syndrome. For the future our findings need
      to be validated in dry eye patients.

PMID- 24940759
TI  - [Update on corneal dystrophies: new insights following first publication of the
      IC3D classification].
AB  - In this review we summarise the new insights into corneal dystrophies following
      publication of the IC3D classification in 2008. Topics covered are new mutations,
      new clinical/histological phenotypes, first descriptions of known mutations in
      previously not mentioned ethnic groups, new dystrophic entities after modern
      corneal surgery and potentially new types of conservative therapy. 

PMID- 24940760
TI  - [Corneal cross-linking in microbial keratitis to prevent a chaud keratoplasty: a
      retrospective case series].
AB  - BACKGROUND: Corneal cross-linking (CXL) with riboflavin is being used more
      frequently for the treatment of therapy-resistant microbial keratitis, since
      increasing drug resistance and specific pathogens, e.g. contact lens-associated
      Acanthamoeba, make this therapy appear as an attractive option to avoid a
      keratoplasty a chaud. PATIENTS AND METHODS: This retrospective case series of 11
      consecutive patients (4 women, 7 men, aged 24-82 years) who received standardised
      antimicrobial CXL for therapy-resistant keratitis to avoid a keratoplasty a
      chaud, included 4 cases with detection of bacterial pathogens, one case with
      proven fungal infection and 6 cases without pathogen detection. Analysed data
      comprised ophthalmic medical history, general risk factors for microbial
      keratitis, treatment before and after CXL. The characterisation of the corneal
      ulcer included photometric measurements of the infiltrates with a median of 16.2
      mm2 and four unmeasurable cases due to extended, not circumscribed lesions.
      RESULTS: Within the follow-up period (mean 134 +/- standard deviation 82 days), a
      penetrating keratoplasty was successfully avoided in 6 patients (55 %). After CXL
      9 patients (82 %) received additionally amniotic membrane transplantation. After
      CXL treatment, topical antibiotic therapy was continued for a mean 27 +/- 13 days
      postoperatively. Steroids were applied in 91 % of the patients. The cornea
      cleared at least to some extent in 9 patients (82 %). Patients with neurotrophic
      keratopathy or potentially compromised immune system showed no increased failure
      rate. CONCLUSION: These results suggest that antimicrobial CXL might be a useful
      option in patients with therapy-resistant corneal ulcer in order to avoid a
      perforating keratoplasty a chaud. For a comprehensive scientific assessment of
      this therapy, however, further, ideally prospective randomised interventional
      studies with large sample sizes are needed.

PMID- 24940761
TI  - [New nanofibrous scaffold for corneal tissue engineering].
AB  - BACKGROUND: An estimated 10 million people suffer worldwide from vision loss
      caused by corneal damage. For the worst cases, the only available treatment is
      transplantation with human donor corneal tissue. However, in numerous countries
      there is a considerable shortage of corneal tissue of good quality, leading to
      various efforts to develop tissue substitutes. The present study aims to
      introduce a nanofibrous scaffold of poly(glycerol sebacate) PGS as a
      biodegradable implant, for the corneal tissue engineering. MATERIALS AND METHODS:
      Nanofibrous scaffolds were produced from PGS and poly(epsilon-caprolactone) (PCL)
      by a modified electro-spinning process. The biocompatibility of the material was
      tested in vitro by colorimetric MTT assay on days 3, 5, and 7 to test the cell
      viability of human corneal endothelium cells (HCEC). To examine a potential
      immunological reaction of the scaffolds, samples were exposed to mononuclear
      cells derived from peripheral blood (PBMCs). After an incubation period of 3
      days, supernatants were assayed for apoptotic assessment and immunogenic
      potentials by annexin V FITC//propidium iodide and flow-cytometric analysis.
      RESULTS: We could successfully demonstrate that cultivation of HCECs on PGS/PCL
      scaffolds was possible. Compared to day 3, cell density determined by microplate
      absorbance was significantly higher after 7 days of cultivation (p < 0.0001).
      According to the MTT data, none of the samples showed toxicity. Apoptotic
      assessments by FACS analysis showed that no composition stimulated apoptosis or
      activated PBMCs occurred. All the compositions were inert for native as well as
      activated T/B/NK cells and monocytes. It can be concluded that leukocytes and
      their activity was not affected by the scaffolds. CONCLUSION: A tissue-like
      scaffold mimicking the human stroma could be developed. The results indicate that
      PGS/PCL scaffolds could be considered as ideal candidates for corneal tissue
      engineering as they are biocompatible in contact to corneal endothelial cells and
      blood cells.

PMID- 24940762
TI  - [Evaluation and quality assurance of refractive surgical interventions by the
      German Ophthalmology Society and the German Professional Association of
      Ophthalmologists (status 2014)].

PMID- 24940763
TI  - [Recommendations of the German Ophthalmology Society on publication guidelines of
      multicenter studies].

PMID- 24940764
TI  - CTLA-4 SNPs (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and systemic lupus
      erythematosus: a meta-analysis.
AB  - In this meta-analysis, we investigated the association between CTLA-4
      polymorphisms (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and SLE susceptibility.
      Data were extracted independently by two reviewers. The odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated in fixed or random effects models.
      Seventeen studies involving of 3931 cases and 4619 controls were identified.
      Significant association of promoter -1722T/C polymorphism and SLE was observed
      for TT vs. CC (OR=1.63, 95% CI 1.63-2. 30, P<0.05) in the overall study
      population and in the Asians subgroups (OR=2. 18, 95% CI 1.70-2. 81, P<0.05); the
      OR for the allele T vs. C in Asians was 1.66 (95% CI 1.33-2. 07, P<0.05). For the
      CT60A/G polymorphism, significant association was observed for AA vs. AG
      (OR=0.64, 95% CI 0.46-0.88, P<0.05) in Asians. These results suggest that 
      1722T/C and CT60A/G polymorphisms in CTLA-4 are associated with SLE, particularly
      in Asians. 

PMID- 24940766
TI  - Signal molecule-dependent quorum-sensing and quorum-quenching enzymes in
      bacteria.
AB  - The quick spread of nosocomial bacterial infections and the increasing prevalence
      of drugresistant strains make the development of novel drugs for pathogens an
      urgent priority. Quorum sensing (QS) is a communication mechanism used by
      bacteria to recognize population density fluctuations and control gene
      expression, which play a critical role both in intraspecies and interspecies
      communications and regulates microbe-host interactions. Low-molecular-weight
      signal compounds, such as acyl-homoserine lactone and autoinducing peptide, are
      used by QS to control the expression of different pathogenic factors. Thus QS-
      and QS signal molecules in particular--is an attractive target for developing
      novel antimicrobial methods. Quorum-quenching enzymes, which hydrolyze or modify
      signal molecules in QS circuit systems to inhibit the expression of bacteria
      virulence factors, have been identified both in prokaryotes and eukaryotes.
      Understanding the mechanism of action of quorum-quenching enzymes also provides a
      promising means to control bacterial infection. This review first introduces the
      novel principle underling signal-based QS systems in several important pathogens
      and then focuses on the newly identified quorum-quenching enzymes, including
      lactonases, acylases, oxidoreductases, and paraoxonases; this summary introduces
      new concepts of antimicrobial infection.

PMID- 24940767
TI  - Aberrant regulation of alternative pre-mRNA splicing in hepatocellular carcinoma.
AB  - Alternative splicing of precursors messenger RNA (pre-mRNA) is commonly used to
      increase the diversity of messenger RNAs expressed by the genome in normal
      multicellular organisms. Dysregulation of alternative splicing underlies a number
      of human diseases, including cancers. Increasing evidence supports the important
      role of this expansive layer of gene regulation in hepatocarcinogenesis.
      Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide
      because of its aggressive property and limited therapeutic options. Studies
      suggest that aberrant alternative splicing promotes generation of oncogenic
      variants in HCC, whereas tumor suppressors are self-inactivated by aberrant
      alternative splicing in HCC. Moreover, different spliced variants of the same
      gene can display distinct and even antagonistic biological functions in HCC. As a
      result, inhibiting the splicing of oncogenic variants and the self-inactivation
      of tumor suppressors are likely to be new therapy strategies. This review
      provides a perspective of the emerging evidence of both alternative splicing as a
      critical mechanism for the development of HCC and that potential cross-talk
      through signaling pathways among different variants might aid in the development
      of novel molecular targets of HCC. 

PMID- 24940765
TI  - HITS-CLIP and PAR-CLIP advance viral miRNA targetome analysis.
AB  - MiRNAs regulate gene expression by binding predominantly to the 3' untranslated
      region (UTR) of target transcripts to prevent their translation and/or induce
      target degradation. In addition to the more than 1200 human miRNAs, human DNA
      tumor viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein
      Barr virus (EBV) encode miRNAs. Target predictions indicate that each miRNA
      targets hundreds of transcripts, many of which are regulated by multiple miRNAs.
      Thus, target identification is a big challenge for the field. Most methods used
      currently investigate single miRNA-target interactions and are not able to
      analyze complex miRNA-target networks. To overcome these challenges, cross
      linking and immunoprecipitation (CLIP), a recently developed method to study
      direct RNA-protein interactions in living cells, has been successfully applied to
      miRNA target analysis. It utilizes Argonaute (Ago)-immunoprecipitation to isolate
      native Ago-miRNA-mRNA complexes. In four recent publications, two variants of the
      CLIP method (HITS-CLIP and PAR-CLIP) were utilized to determine the targetomes of
      human and viral miRNAs in cells infected with the gamma-herpesviruses KSHV and
      EBV, which are associated with a number of human cancers. Here, we briefly
      introduce herpesvirus-encoded miRNAs and then focus on how CLIP technology has
      largely impacted our understanding of viral miRNAs in viral biology and
      pathogenesis. 

PMID- 24940768
TI  - SWI/SNF chromatin remodeling enzymes in melanocyte differentiation and melanoma.
AB  - Epidermal melanocytes are pigment-producing cells derived from the neural crest
      that protects skin from the damaging effects of solar radiation. Malignant
      melanoma, a highly aggressive cancer, arises from melanocytes. SWI/SNF enzymes
      are multiprotein complexes that remodel chromatin structure and have extensive
      roles in cellular differentiation. Components of the complex have been found to
      be mutated or lost in several human cancers. This review focuses on studies that
      implicate SWI/SNF enzymes in melanocyte differentiation and in melanoma. 

PMID- 24940769
TI  - Comparative genomics of Mycobacterium tuberculosis drug efflux pumps and their
      transcriptional regulators.
AB  - Efflux pump systems are important in general drug resistance. Understanding
      efflux pumps can inform drug target selection and novel antibiotics designs. In
      this review, we have summarized the physiological roles, types, and mechanisms of
      drug efflux pumps. Mycobacterium tuberculosis is the causative agent of
      tuberculosis, a global threat to public health, and the increasing resistance of
      this mycobacterium to antibiotics is alarming. Therefore, we have focused on the
      comparative genomics of efflux pumps and relevant transcriptional regulators of
      M. tuberculosis. 

PMID- 24940770
TI  - Coupling between neurotransmitter translocation and protonation state of a
      titratable residue during Na +-coupled transport.

PMID- 24940771
TI  - How fast is your camera? Timescales for molecular motion and their role in
      restraining molecular dynamics.

PMID- 24940772
TI  - Does the sodium pump have secret levels?

PMID- 24940773
TI  - Sodium and proton effects on inward proton transport through Na/K pumps.
AB  - The Na/K pump hydrolyzes ATP to export three intracellular Na (Nai) as it imports
      two extracellular K (Ko) across animal plasma membranes. Within the protein, two
      ion-binding sites (sites I and II) can reciprocally bind Na or K, but a third
      site (site III) exclusively binds Na in a voltage-dependent fashion. In the
      absence of Nao and Ko, the pump passively imports protons, generating an inward
      current (IH). To elucidate the mechanisms of IH, we used voltage-clamp techniques
      to investigate the [H]o, [Na]o, and voltage dependence of IH in Na/K pumps from
      ventricular myocytes and in ouabain-resistant pumps expressed in Xenopus oocytes.
      Lowering pHo revealed that Ho both activates IH (in a voltage-dependent manner)
      and inhibits it (in a voltage-independent manner) by binding to different sites.
      Nao effects depend on pHo; at pHo where no Ho inhibition is observed, Nao
      inhibits IH at all concentrations, but when applied at pHo that inhibits pump
      mediated current, low [Na]o activates IH and high [Na]o inhibits it. Our results
      demonstrate that IH is a property inherent to Na/K pumps, not linked to the
      oocyte expression environment, explains differences in the characteristics of IH
      previously reported in the literature, and supports a model in which 1), protons
      leak through site III; 2), binding of two Na or two protons to sites I and II
      inhibits proton transport; and 3), pumps with mixed Na/proton occupancy of sites
      I and II remain permeable to protons.

PMID- 24940774
TI  - Structural dynamics and conformational equilibria of SERCA regulatory proteins in
      membranes by solid-state NMR restrained simulations.
AB  - Solid-state NMR spectroscopy is emerging as a powerful approach to determine
      structure, topology, and conformational dynamics of membrane proteins at the
      atomic level. Conformational dynamics are often inferred and quantified from the
      motional averaging of the NMR parameters. However, the nature of these motions is
      difficult to envision based only on spectroscopic data. Here, we utilized
      restrained molecular dynamics simulations to probe the structural dynamics,
      topology and conformational transitions of regulatory membrane proteins of the
      calcium ATPase SERCA, namely sarcolipin and phospholamban, in explicit lipid
      bilayers. Specifically, we employed oriented solid-state NMR data, such as
      dipolar couplings and chemical shift anisotropy measured in lipid bicelles, to
      refine the conformational ensemble of these proteins in lipid membranes. The
      samplings accurately reproduced the orientations of transmembrane helices and
      showed a significant degree of convergence with all of the NMR parameters. Unlike
      the unrestrained simulations, the resulting sarcolipin structures are in
      agreement with distances and angles for hydrogen bonds in ideal helices. In the
      case of phospholamban, the restrained ensemble sampled the conformational
      interconversion between T (helical) and R (unfolded) states for the cytoplasmic
      region that could not be observed using standard structural refinements with the
      same experimental data set. This study underscores the importance of implementing
      NMR data in molecular dynamics protocols to better describe the conformational
      landscapes of membrane proteins embedded in realistic lipid membranes. 

PMID- 24940775
TI  - Membrane permeabilization induced by sphingosine: effect of negatively charged
      lipids.
AB  - Sphingosine [(2S, 3R, 4E)-2-amino-4-octadecen-1, 3-diol] is the most common
      sphingoid long chain base in sphingolipids. It is the precursor of important cell
      signaling molecules, such as ceramides. In the last decade it has been shown to
      act itself as a potent metabolic signaling molecule, by activating a number of
      protein kinases. Moreover, sphingosine has been found to permeabilize
      phospholipid bilayers, giving rise to vesicle leakage. The present contribution
      intends to analyze the mechanism by which this bioactive lipid induces vesicle
      contents release, and the effect of negatively charged bilayers in the release
      process. Fluorescence lifetime measurements and confocal fluorescence microscopy
      have been applied to observe the mechanism of sphingosine efflux from large and
      giant unilamellar vesicles; a graded-release efflux has been detected.
      Additionally, stopped-flow measurements have shown that the rate of vesicle
      permeabilization increases with sphingosine concentration. Because at the
      physiological pH sphingosine has a net positive charge, its interaction with
      negatively charged phospholipids (e.g., bilayers containing phosphatidic acid
      together with sphingomyelins, phosphatidylethanolamine, and cholesterol) gives
      rise to a release of vesicular contents, faster than with electrically neutral
      bilayers. Furthermore, phosphorous 31-NMR and x-ray data show the capacity of
      sphingosine to facilitate the formation of nonbilayer (cubic phase) intermediates
      in negatively charged membranes. The data might explain the pathogenesis of
      Niemann-Pick type C1 disease.

PMID- 24940776
TI  - Amyloids of alpha-synuclein affect the structure and dynamics of supported lipid
      bilayers.
AB  - Interactions of monomeric alpha-synuclein (alphaS) with lipid membranes have been
      suggested to play an important role in initiating aggregation of alphaS. We have
      systematically analyzed the distribution and self-assembly of monomeric alphaS on
      supported lipid bilayers. We observe that at protein/lipid ratios higher than
      1:10, alphaS forms micrometer-sized clusters, leading to observable membrane
      defects and decrease in lateral diffusion of both lipids and proteins. An alphaS
      deletion mutant lacking amino-acid residues 71-82 binds to membranes, but does
      not observably affect membrane integrity. Although this deletion mutant cannot
      form amyloid, significant amyloid formation is observed in the wild-type alphaS
      clusters. These results suggest that the process of amyloid formation, rather
      than binding of alphaS on membranes, is crucial in compromising membrane
      integrity. 

PMID- 24940777
TI  - Effect of oxidation on the structure of human low- and high-density lipoproteins.
AB  - This work presents a controlled study of low-density lipoprotein (LDL) and high
      density lipoprotein (HDL) structural changes due to in vitro oxidation with
      copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and
      dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS,
      and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to
      our knowledge new deconvolution method. This method provides the electron density
      profile of the samples directly from the intensity scattering of the monomers.
      Results show that LDL particles oxidized for 18 h show significant structural
      changes when compared to nonoxidized particles. Changes were observed in the
      electrical density profile, in size polydispersity, and in the degree of
      flexibility of the APO-B protein on the particle. HDL optical results obtained
      with the ZS technique showed a decrease of the amplitude of the nonlinear optical
      signal as a function of oxidation time. In contrast to LDL results reported in
      the literature, the HDL ZS signal does not lead to a complete loss of nonlinear
      optical signal after 18 h of copper oxidation. Also, the SAXS results did not
      indicate significant structural changes due to oxidation of HDL particles, and
      DLS results showed that a small number of oligomers formed in the sample oxidized
      for 18 h. All experimental results for the HDL samples indicate that this
      lipoprotein is more resistant to the oxidation process than are LDL particles.

PMID- 24940778
TI  - N-nervonoylsphingomyelin (C24:1) prevents lateral heterogeneity in cholesterol
      containing membranes.
AB  - This study was conducted to explore how the nature of the acyl chains of
      sphingomyelin (SM) influence its lateral distribution in the ternary lipid
      mixture SM/cholesterol/1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), focusing
      on the importance of the hydrophobic part of the SM molecule for domain
      formation. Atomic force microscopy (AFM) measurements showed that the presence of
      a double bond in the 24:1 SM molecule in mixtures with cholesterol (CHO) or in
      pure bilayers led to a decrease in the molecular packing. Confocal microscopy and
      AFM showed, at the meso- and nanoscales respectively, that unlike 16:0 and 24:0
      SM, 24:1 SM does not induce phase segregation in ternary lipid mixtures with DOPC
      and CHO. This ternary lipid mixture had a nanomechanical stability intermediate
      between those displayed by liquid-ordered (Lo) and liquid-disordered (Ld) phases,
      as reported by AFM force spectroscopy measurements, demonstrating that 24:1 SM is
      able to accommodate both DOPC and CHO, forming a single phase. Confocal
      experiments on giant unilamellar vesicles made of human, sheep, and rabbit
      erythrocyte ghosts rich in 24:1 SM and CHO, showed no lateral domain segregation.
      This study provides insights into how the specific molecular structure of SM
      affects the lateral behavior and the physical properties of both model and
      natural membranes. Specifically, the data suggest that unsaturated SM may help to
      keep membrane lipids in a homogeneous mixture rather than in separate domains. 

PMID- 24940779
TI  - Molecular mechanism of the synergistic effects of vitrification solutions on the
      stability of phospholipid bilayers.
AB  - The vitrification solutions used in the cryopreservation of biological samples
      aim to minimize the deleterious formation of ice by dehydrating cells and
      promoting the formation of the glassy state of water. They contain a mixture of
      different cryoprotective agents (CPAs) in water, typically polyhydroxylated
      alcohols and/or dimethyl sulfoxide (DMSO), which can damage cell membranes.
      Molecular dynamics simulations have been used to investigate the behavior of pure
      DPPC, pure DOPC, and mixed DOPC-beta-sitosterol bilayers solvated in a
      vitrification solution containing glycerol, ethylene glycol, and DMSO at
      concentrations that approximate the widely used plant vitrification solution 2.
      As in the case of solutions containing a single CPA, the vitrification solution
      causes the bilayer to thin and become disordered, and pores form in the case of
      some bilayers. Importantly, the degree of thinning is, however, substantially
      reduced compared to solutions of DMSO containing the same total CPA
      concentration. The reduction in the damage done to the bilayers is a result of
      the ability of the polyhydroxylated species (especially glycerol) to form
      hydrogen bonds to the lipid and sterol molecules of the bilayer. A decrease in
      the amount of DMSO in the vitrification solution with a corresponding increase in
      the amount of glycerol or ethylene glycol diminishes further its damaging effect
      due to increased hydrogen bonding of the polyol species to the bilayer
      headgroups. These findings rationalize, to our knowledge for the first time, the
      synergistic effects of combining different CPAs, and form the basis for the
      optimization of vitrification solutions. 

PMID- 24940780
TI  - Lateral motion and bending of microtubules studied with a new single-filament
      tracking routine in living cells.
AB  - The cytoskeleton is involved in numerous cellular processes such as migration,
      division, and contraction and provides the tracks for transport driven by
      molecular motors. Therefore, it is very important to quantify the mechanical
      behavior of the cytoskeletal filaments to get a better insight into cell
      mechanics and organization. It has been demonstrated that relevant mechanical
      properties of microtubules can be extracted from the analysis of their motion and
      shape fluctuations. However, tracking individual filaments in living cells is
      extremely complex due, for example, to the high and heterogeneous background. We
      introduce a believed new tracking algorithm that allows recovering the
      coordinates of fluorescent microtubules with ~9 nm precision in in vitro
      conditions. To illustrate potential applications of this algorithm, we studied
      the curvature distributions of fluorescent microtubules in living cells. By
      performing a Fourier analysis of the microtubule shapes, we found that the
      curvatures followed a thermal-like distribution as previously reported with an
      effective persistence length of ~20 MUm, a value significantly smaller than that
      measured in vitro. We also verified that the microtubule-associated protein XTP
      or the depolymerization of the actin network do not affect this value; however,
      the disruption of intermediate filaments decreased the persistence length. Also,
      we recovered trajectories of microtubule segments in actin or intermediate
      filament-depleted cells, and observed a significant increase of their motion with
      respect to untreated cells showing that these filaments contribute to the overall
      organization of the microtubule network. Moreover, the analysis of trajectories
      of microtubule segments in untreated cells showed that these filaments presented
      a slower but more directional motion in the cortex with respect to the
      perinuclear region, and suggests that the tracking routine would allow mapping
      the microtubule dynamical organization in cells.

PMID- 24940781
TI  - Effects of alpha-tubulin K40 acetylation and detyrosination on kinesin-1 motility
      in a purified system.
AB  - Long-range transport in cells is achieved primarily through motor-based transport
      along a network of microtubule tracks. Targeted transport by kinesin motors can
      be correlated with posttranslational modifications (PTMs) of the tubulin subunits
      in specific microtubules. To directly examine the influence of specific PTMs on
      kinesin-1 motility, we generated tubulin subunits that were either enriched in or
      lacking acetylation of alpha-tubulin lysine 40 (K40) or detyrosination of the
      alpha-tubulin C-terminal tail. We show that K40 acetylation does not result in
      significant changes in kinesin-1's landing rate or motility parameters (velocity
      and run length) across experimental conditions. In contrast, detyrosination
      causes a moderate increase in kinesin-1's landing rate. The fact that the effects
      of detyrosination are dampened by prior K40 acetylation indicates that the
      combination of PTMs may be an important aspect of the functional output of
      microtubule heterogeneity. Importantly, our results indicate that the moderate
      influences that single PTMs have on kinesin-1 in vitro do not explain the strong
      correlation between specific PTMs and kinesin-1 transport in cells. Thus,
      additional mechanisms for regulating kinesin-1 transport in cells must be
      explored in future work. 

PMID- 24940782
TI  - Replica exchange molecular dynamics simulations provide insight into substrate
      recognition by small heat shock proteins.
AB  - The small heat shock proteins (sHSPs) are a virtually ubiquitous and diverse
      group of molecular chaperones that can bind and protect unfolding proteins from
      irreversible aggregation. It has been suggested that intrinsic disorder of the N
      terminal arm (NTA) of sHSPs is important for substrate recognition. To
      investigate conformations of the NTA that could recognize substrates we performed
      replica exchange molecular dynamics simulations. Behavior at normal and stress
      temperatures of the dimeric building blocks of dodecameric HSPs from wheat
      (Ta16.9) and pea (Ps18.1) were compared because they display high sequence
      similarity, but Ps18.1 is more efficient in binding specific substrates. In our
      simulations, the NTAs of the dimer are flexible and dynamic; however, rather than
      exhibiting highly extended conformations they retain considerable alpha-helical
      character and contacts with the conserved alpha-crystallin domain (ACD). Network
      analysis and clustering methods reveal that there are two major conformational
      forms designated either "open" or "closed" based on the relative position of the
      two NTAs and their hydrophobic solvent accessible surface area. The equilibrium
      constant for the closed to open transition is significantly different for Ta16.9
      and Ps18.1, with the latter showing more open conformations at elevated
      temperature correlated with its more effective chaperone activity. In addition,
      the Ps18.1 NTAs have more hydrophobic solvent accessible surface than those of
      Ta16.9. NTA hydrophobic patches are comparable in size to the area buried in many
      protein-protein interactions, which would enable sHSPs to bind early unfolding
      intermediates. Reduced interactions of the Ps18.1 NTAs with each other and with
      the ACD contribute to the differences in dynamics and hydrophobic surface area of
      the two sHSPs. These data support a major role for the conformational equilibrium
      of the NTA in substrate binding and indicate features of the NTA that contribute
      to sHSP chaperone efficiency.

PMID- 24940783
TI  - Features of large hinge-bending conformational transitions. Prediction of closed
      structure from open state.
AB  - We performed a detailed analysis of conformational transition pathways for a set
      of 10 proteins, which undergo large hinge-bending-type motions with 4-12 A RMSD
      (root mean-square distance) between open and closed crystal structures.
      Anisotropic network model-Monte Carlo (ANM-MC) algorithm generates a targeted
      pathway between two conformations, where the collective modes from the ANM are
      used for deformation at each iteration and the conformational energy of the
      deformed structure is minimized via an MC algorithm. The target structure was
      approached successfully with an RMSD of 0.9-4.1 A when a relatively low cutoff
      radius of 10 A was used in ANM. Even though one predominant mode (first or
      second) directed the open-to-closed conformational transition, changes in the
      dominant mode character were observed for most cases along the transition. By
      imposing radius of gyration constraint during mode selection, it was possible to
      predict the closed structure for eight out of 10 proteins (with initial 4.1-7.1 A
      and final 1.7-2.9 A RMSD to target). Deforming along a single mode leads to most
      successful predictions. Based on the previously reported free energy surface of
      adenylate kinase, deformations along the first mode produced an energetically
      favorable path, which was interestingly facilitated by a change in mode shape
      (resembling second and third modes) at key points. Pathway intermediates are
      provided in our database of conformational transitions
      (http://safir.prc.boun.edu.tr/anmmc/method/1).

PMID- 24940784
TI  - Rigidity, secondary structure, and the universality of the boson peak in
      proteins.
AB  - Complementary neutron- and light-scattering results on nine proteins and amino
      acids reveal the role of rigidity and secondary structure in determining the time
      and lengthscales of low-frequency collective vibrational dynamics in proteins.
      These dynamics manifest in a spectral feature, known as the boson peak (BP),
      which is common to all disordered materials. We demonstrate that BP position
      scales systematically with structural motifs, reflecting local rigidity:
      disordered proteins appear softer than alpha-helical proteins; which are softer
      than beta-sheet proteins. Our analysis also reveals a universal spectral shape of
      the BP in proteins and amino acid mixtures; superimposable on the shape observed
      in typical glasses. Uniformity in the underlying physical mechanism, independent
      of the specific chemical composition, connects the BP vibrations to nanometer
      scale heterogeneities, providing an experimental benchmark for coarse-grained
      simulations, structure/rigidity relationships, and engineering of proteins for
      novel applications. 

PMID- 24940785
TI  - Molecular dynamics simulations elucidate the mechanism of proton transport in the
      glutamate transporter EAAT3.
AB  - The uptake of glutamate in nerve synapses is carried out by the excitatory amino
      acid transporters (EAATs), involving the cotransport of a proton and three Na(+)
      ions and the countertransport of a K(+) ion. In this study, we use an EAAT3
      homology model to calculate the pKa of several titratable residues around the
      glutamate binding site to locate the proton carrier site involved in the
      translocation of the substrate. After identifying E374 as the main candidate for
      carrying the proton, we calculate the protonation state of this residue in
      different conformations of EAAT3 and with different ligands bound. We find that
      E374 is protonated in the fully bound state, but removing the Na2 ion and the
      substrate reduces the pKa of this residue and favors the release of the proton to
      solution. Removing the remaining Na(+) ions again favors the protonation of E374
      in both the outward- and inward-facing states, hence the proton is not released
      in the empty transporter. By calculating the pKa of E374 with a K(+) ion bound in
      three possible sites, we show that binding of the K(+) ion is necessary for the
      release of the proton in the inward-facing state. This suggests a mechanism in
      which a K(+) ion replaces one of the ligands bound to the transporter, which may
      explain the faster transport rates of the EAATs compared to its archaeal
      homologs. 

PMID- 24940786
TI  - Arterial extracellular matrix: a mechanobiological study of the contributions and
      interactions of elastin and collagen.
AB  - The complex network structure of elastin and collagen extracellular matrix (ECM)
      forms the primary load bearing components in the arterial wall. The structural
      and mechanobiological interactions between elastin and collagen are important for
      properly functioning arteries. Here, we examined the elastin and collagen
      organization, realignment, and recruitment by coupling mechanical loading and
      multiphoton imaging. Two-photon excitation fluorescence and second harmonic
      generation methods were performed with a multiphoton video-rate microscope to
      capture real time changes to the elastin and collagen structure during biaxial
      deformation. Enzymatic removal of elastin was performed to assess the structural
      changes of the remaining collagen structure. Quantitative analysis of the
      structural changes to elastin and collagen was made using a combination of two
      dimensional fast Fourier transform and fractal analysis, which allows for a more
      complete understanding of structural changes. Our study provides new quantitative
      evidence, to our knowledge on the sequential engagement of different arterial ECM
      components in response to mechanical loading. The adventitial collagen exists as
      large wavy bundles of fibers that exhibit fiber engagement after 20% strain. The
      medial collagen is engaged throughout the stretching process, and prominent
      elastic fiber engagement is observed up to 20% strain after which the engagement
      plateaus. The fiber orientation distribution functions show remarkably different
      changes in the ECM structure in response to mechanical loading. The medial
      collagen shows an evident preferred circumferential distribution, however the
      fiber families of adventitial collagen are obscured by their waviness at no or
      low mechanical strains. Collagen fibers in both layers exhibit significant
      realignment in response to unequal biaxial loading. The elastic fibers are much
      more uniformly distributed and remained relatively unchanged due to loading.
      Removal of elastin produces similar structural changes in collagen as mechanical
      loading. Our study suggests that the elastic fibers are under tension and impart
      an intrinsic compressive stress on the collagen. 

PMID- 24940787
TI  - The influence of Ca2+ buffers on free [Ca2+] fluctuations and the effective
      volume of Ca2+ microdomains.
AB  - Intracellular calcium (Ca(2+)) plays a significant role in many cell signaling
      pathways, some of which are localized to spatially restricted microdomains.
      Ca(2+) binding proteins (Ca(2+) buffers) play an important role in regulating
      Ca(2+) concentration ([Ca(2+)]). Buffers typically slow [Ca(2+)] temporal
      dynamics and increase the effective volume of Ca(2+) domains. Because
      fluctuations in [Ca(2+)] decrease in proportion to the square-root of a domain's
      physical volume, one might conjecture that buffers decrease [Ca(2+)] fluctuations
      and, consequently, mitigate the significance of small domain volume concerning
      Ca(2+) signaling. We test this hypothesis through mathematical and computational
      analysis of idealized buffer-containing domains and their stochastic dynamics
      during free Ca(2+) influx with passive exchange of both Ca(2+) and buffer with
      bulk concentrations. We derive Langevin equations for the fluctuating dynamics of
      Ca(2+) and buffer and use these stochastic differential equations to determine
      the magnitude of [Ca(2+)] fluctuations for different buffer parameters (e.g.,
      dissociation constant and concentration). In marked contrast to expectations
      based on a naive application of the principle of effective volume as employed in
      deterministic models of Ca(2+) signaling, we find that mobile and rapid buffers
      typically increase the magnitude of domain [Ca(2+)] fluctuations during periods
      of Ca(2+) influx, whereas stationary (immobile) Ca(2+) buffers do not. Also
      contrary to expectations, we find that in the absence of Ca(2+) influx, buffers
      influence the temporal characteristics, but not the magnitude, of [Ca(2+)]
      fluctuations. We derive an analytical formula describing the influence of rapid
      Ca(2+) buffers on [Ca(2+)] fluctuations and, importantly, identify the stochastic
      analog of (deterministic) effective domain volume. Our results demonstrate that
      Ca(2+) buffers alter the dynamics of [Ca(2+)] fluctuations in a nonintuitive
      manner. The finding that Ca(2+) buffers do not suppress intrinsic domain [Ca(2+)]
      fluctuations raises the intriguing question of whether or not [Ca(2+)]
      fluctuations are a physiologically significant aspect of local Ca(2+) signaling. 

PMID- 24940788
TI  - Drag of the cytosol as a transport mechanism in neurons.
AB  - Axonal transport is typically divided into two components, which can be
      distinguished by their mean velocity. The fast component includes steady
      trafficking of different organelles and vesicles actively transported by motor
      proteins. The slow component comprises nonmembranous materials that undergo
      infrequent bidirectional motion. The underlying mechanism of slow axonal
      transport has been under debate during the past three decades. We propose a
      simple displacement mechanism that may be central for the distribution of
      molecules not carried by vesicles. It relies on the cytoplasmic drag induced by
      organelle movement and readily accounts for key experimental observations
      pertaining to slow-component transport. The induced cytoplasmic drag is predicted
      to depend mainly on the distribution of microtubules in the axon and the
      organelle transport rate.

PMID- 24940789
TI  - Paradoxical results in perturbation-based signaling network reconstruction.
AB  - Mathematical models are extensively employed to understand physicochemical
      processes in biological systems. In the absence of detailed mechanistic
      knowledge, models are often based on network inference methods, which in turn
      rely upon perturbations to nodes by biochemical means. We have discovered a
      potential pitfall of the approach underpinning such methods when applied to
      signaling networks. We first show experimentally, and then explain
      mathematically, how even in the simplest signaling systems, perturbation methods
      may lead to paradoxical conclusions: for any given pair of two components X and
      Y, and depending upon the specific intervention on Y, either an activation or a
      repression of X could be inferred. This effect is of a different nature from
      incomplete network identification due to underdetermined data and is a phenomenon
      intrinsic to perturbations. Our experiments are performed in an in vitro minimal
      system, thus isolating the effect and showing that it cannot be explained by
      feedbacks due to unknown intermediates. Moreover, our in vitro system utilizes
      proteins from a pathway in mammalian (and other eukaryotic) cells that play a
      central role in proliferation, gene expression, differentiation, mitosis, cell
      survival, and apoptosis. This pathway is the perturbation target of contemporary
      therapies for various types of cancers. The results presented here show that the
      simplistic view of intracellular signaling networks being made up of activation
      and repression links is seriously misleading, and call for a fundamental
      rethinking of signaling network analysis and inference methods.

PMID- 24940790
TI  - AutoTT: automated detection and analysis of T-tubule architecture in
      cardiomyocytes.
AB  - Cardiac transverse (T)-tubules provide a specialized structure for
      synchronization and stabilization of sarcoplasmic reticulum Ca(2+) release in
      healthy cardiomyocytes. The application of laser scanning confocal microscopy and
      the use of fluorescent lipophilic membrane dyes have boosted the discoveries that
      T-tubule remodeling is a significant factor contributing to cardiac contractile
      dysfunction. However, the analysis and quantification of the remodeling of T
      tubules have been a challenge and remain inconsistent among different research
      laboratories. Fast Fourier transformation (FFT) is the major analysis method
      applied to calculate the spatial frequency spectrum, which is used to represent
      the regularity of T-tubule systems. However, this approach is flawed because the
      density of T-tubules as well as non-T-tubule signals in the images influence the
      spectrum power generated by FFT. Preprocessing of images and topological
      architecture extracting is necessary to remove non-T-tubule noise from the
      analysis. In addition, manual analysis of images is time consuming and prone to
      errors and investigator bias. Therefore, we developed AutoTT, an automated
      analysis program that incorporates image processing, morphological feature
      extraction, and FFT analysis of spectrum power. The underlying algorithm is
      implemented in MATLAB (The MathWorks, Natick, MA). The program outputs the
      densities of transversely oriented T-tubules and longitudinally oriented T
      tubules, power spectrum of the overall T-tubule systems, and averaged spacing of
      T-tubules. We also combined the density and regularity of T-tubules to give an
      index of T-tubule integrity (TTint), which provides a global evaluation of T
      tubule alterations. In summary, AutoTT provides a reliable, easy to use, and fast
      approach for analyzing myocyte T-tubules. This program can also be applied to
      measure the density and integrity of other cellular structures.

PMID- 24940792
TI  - Intervention fidelity: developing an experience-based model for rehabilitation
      research.
AB  - BACKGROUND: Intervention fidelity is concerned with the extent to which
      interventions are implemented as intended. Consideration of fidelity is essential
      if the conclusions of effectiveness studies are to be credible, but little
      attention has been given to it in the rehabilitation literature. We describe our
      experiences addressing fidelity in the development of a rehabilitation clinical
      trial, and consider how an existing model of fidelity may be employed in
      rehabilitation research. METHODS: We used a model and methods drawn from the
      psychology literature to investigate how fidelity might be maximised during the
      planning and development of a stroke rehabilitation trial. We considered fidelity
      in intervention design, provider training, and the behaviour of providers and
      participants. We also evaluated methods of assessing fidelity during a trial.
      RESULTS: We identified strategies to help address fidelity in our trial protocol,
      along with their potential strengths and limitations. We incorporated these
      strategies into a model of fidelity that is appropriate to the concepts and
      language of rehabilitation. CONCLUSION: A range of strategies are appropriate to
      help maximise and measure fidelity in rehabilitation research. Based on our
      experiences, we propose a model of fidelity and provide recommendations to inform
      the growing literature of fidelity in this discipline.

PMID- 24940791
TI  - Type-3 BRET, an improved competition-based bioluminescence resonance energy
      transfer assay.
AB  - We show that in conventional, competition-based bioluminescence resonance energy
      transfer (BRET) assays of membrane protein stoichiometry, the presence of
      competitors can alter tagged-protein density and artifactually reduce energy
      transfer efficiency. A well-characterized monomeric type I membrane protein,
      CD86, and two G protein-coupled receptors beta2AR and mCannR2, all of which
      behave as dimers in these conventional assays, exhibit monomeric behavior in an
      improved competition-based type-3 BRET assay designed to circumvent such
      artifacts. 

PMID- 24940794
TI  - Cognitive and self-reported psychological outcomes of blast-induced mild
      traumatic brain injury in veterans: a preliminary study.
AB  - The increased use of explosives in combat has resulted in a large number of
      returning veterans suffering from blast-related mild traumatic brain injury
      (mTBI) and self-reported complications. It remains unclear whether this increase
      in self-reported difficulties is unique to the blast mechanism or stressful
      preinjury environment and whether cognitive-functioning deficits correspond with
      these difficulties in the postacute phase. This study examined the relationship
      between cognitive performance and self-reported psychological and somatic
      symptoms of blast-related mTBI compared with civilian mTBI, independent of
      comorbid posttraumatic stress disorder (PTSD) symptoms. Twelve veterans with
      blast-related mTBI were compared to 18 individuals with civilian mTBI on
      cognitive tests and self-report questionnaires. Univariate analyses failed to
      reveal differences on any individual cognitive test. Further, veterans reported
      more psychological and somatic complaints. These self-reported difficulties were
      not significantly correlated with neuropsychological performance. Overall,
      preliminary results suggest that in the postacute phase, subjective complaints
      related to blast-related mTBI do not covary with objective cognitive performance.
      Additionally, cognitive outcomes from blast-related mTBI were similar to those of
      civilian forms of mTBI. Future studies should identify the cognitive and self
      reported sequelae of blast-related mTBI independent of comorbid PTSD in a larger
      sample of veterans. 

PMID- 24940795
TI  - Dynamics of the increase in strength and girth of quadriceps muscle after the
      reconstruction of anterior cruciate ligament.
AB  - BACKGROUND: Reconstruction is the method of choice in the treatment of ACL
      rupture. Postoperative rehabilitation is a very important aspect of therapeutic
      management. One of priority elements is to regain proper strength and function of
      the quadriceps muscle in a short time. The aim of this study was to estimate the
      dynamics of the increase in strength and girth of quadriceps after ACL
      reconstruction. MATERIAL AND METHODS: The examined group consisted of 30 patients
      who had undergone arthroscopic assisted quadruple bundle dual channel ACL
      reconstruction surgery in years 2010-2011. The average age of the patients at the
      time of operation was 31.7 years (range 17-53). Each patient was examined 4
      times: before the surgery as well as in the second, sixth and twelfth week after
      the reconstruction. RESULTS: Examination revealed a significant increase in
      quadriceps girth, with peak increase rate observed within the two first weeks
      after the surgery. Between weeks 2 and 6, a decrease in quadriceps girth was
      observed followed by repeated increase worm week 6 on. The greatest increase in
      the girth at the thickest point of the muscle was observed in rehabilitation
      weeks 6 through 12. A significant decrease in muscle strength was observed in the
      first 2 weeks after the surgery. In the remaining periods, the strength of the
      quadriceps muscle continued to grow. The average KSS score increased from 109.1
      at week 2 to 162.3 at week 12 after the surgery. CONCLUSIONS: Rehabilitation
      results in a dynamic increase in the strength of quadriceps between weeks 6 and
      12 following reconstruction of anterior cruciate ligament. However, the 12-week
      rehabilitation period is not sufficient to regain full functionality.

PMID- 24940797
TI  - Reduced adenosine A2a receptor-mediated efferent arteriolar vasodilation
      contributes to diabetes-induced glomerular hyperfiltration.
AB  - Diabetes is associated with increased risk for development of kidney disease, and
      an increased glomerular filtration rate is an early indication of altered kidney
      function. Here we determine whether reduced adenosine A2a receptor-mediated
      vasodilation of the efferent arteriole contributes to the increased glomerular
      filtration rate in diabetes. The glomerular filtration rate, renal blood flow,
      and proximal tubular stop flow pressure were investigated in control and
      streptozotocin-diabetic rats during baseline and after administration of the
      adenosine A2a receptor antagonist ZM241385 or the adenosine A2a receptor agonist
      CGS21680. The diabetes-induced glomerular hyperfiltration was reduced by 24%
      following A2a receptor stimulation but was unaffected by A2a receptor inhibition.
      Contrarily, glomerular filtration rate in controls increased by 22% after A2a
      receptor inhibition and was unaffected by A2a stimulation. The increased
      glomerular filtration rate after A2a receptor inhibition in controls and
      decreased glomerular filtration rate after A2a receptor activation in diabetics
      were caused by increased and decreased stop flow pressure, respectively. None of
      the interventions affected renal blood flow. Thus, the normal adenosine A2a
      receptor-mediated tonic vasodilation of efferent arterioles is abolished in the
      diabetic kidney. This causes increased efferent arteriolar resistance resulting
      in increased filtration fraction and hyperfiltration. 

PMID- 24940798
TI  - Renal denervation has blood pressure-independent protective effects on kidney and
      heart in a rat model of chronic kidney disease.
AB  - We elucidate the underlying mechanisms of bidirectional cardiorenal interaction,
      focusing on the sympathetic nerve driving disruption of the local renin
      angiotensin system (RAS). A rat model of N(omega)-nitro-L-arginine methyl ester
      (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce
      damage in the heart and kidney, similar to cardiorenal syndrome. L-NAME induced
      sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local
      RAS elevations. These were suppressed by bilateral renal denervation, but not by
      hydralazine treatment, despite the blood pressure being kept the same between the
      two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in
      both organs, AGT mRNA decreased in the kidney and increased in the heart in a
      contradictory manner. Immunostaining for AGT suggested that renal denervation
      suppressed AGT onsite generation from activated resident macrophages of the heart
      and circulating AGT excretion from glomeruli of the kidney. We also examined rats
      treated with L-NAME plus unilateral denervation to confirm direct sympathetic
      regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II
      content and the degrees of renal injury from denervated kidneys were less than
      those from contralateral innervated kidneys within the same rats. Thus, renal
      denervation has blood pressure-independent beneficial effects associated with
      local RAS inhibition. 

PMID- 24940796
TI  - The urea decomposition product cyanate promotes endothelial dysfunction.
AB  - The dramatic cardiovascular mortality of patients with chronic kidney disease is
      attributable in a significant proportion to endothelial dysfunction. Cyanate, a
      reactive species in equilibrium with urea, is formed in excess in chronic kidney
      disease. Cyanate is thought to have a causal role in promoting cardiovascular
      disease, but the underlying mechanisms remain unclear. Immunohistochemical
      analysis performed in the present study revealed that carbamylated epitopes
      associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate
      treatment of human coronary artery endothelial cells reduced expression of
      endothelial nitric oxide synthase, and increased tissue factor and plasminogen
      activator inhibitor-1 expression. In mice, administration of cyanate, promoting
      protein carbamylation at levels observed in uremic patients, attenuated arterial
      vasorelaxation of aortic rings in response to acetylcholine without affecting the
      sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase
      and nitric oxide production were significantly reduced in aortic tissue of
      cyanate-treated mice. This coincided with a marked increase of tissue factor and
      plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated
      mice. Thus, cyanate compromises endothelial functionality in vitro and in vivo.
      This may contribute to the dramatic cardiovascular risk of patients suffering
      from chronic kidney disease. 

PMID- 24940799
TI  - Postimplantation X-ray parameters predict functional catheter problems in
      peritoneal dialysis.
AB  - Functional catheter problems are a major challenge for peritoneal dialysis (PD)
      programs. Here we performed a retrospective single-center study of 110
      consecutive patients receiving a first PD catheter (swan neck double-cuff
      Missouri curled catheters, open surgical technique). Using postimplantation X
      ray, the following categories were defined: swan neck angle (posterioanterio view
      (PA): under 45 degrees , 45-90 degrees , over 90 degrees ), inclination (angle
      between intramural part of catheter and horizontal line; lateral view: greater
      than/equal to 30 degrees , under 30 degrees ), and the position of silicone bead
      relative to spine (PA view: L1-2, L3-4, lower) and catheter tip (PA view:
      hypogastric, umbilical, subcostal). Covariates included demographics, body size,
      previous abdominal surgery, and abdominal wall hernias. During a mean follow-up
      of 36 months, the time to first functional catheter problem was significantly
      associated with both the swan neck angle and inclination. The need for surgical
      intervention was significantly associated with inclination only. Technique
      failure was not associated with any parameter. In multivariate analysis,
      inclination was the sole variable significantly associated with functional
      catheter problems (hazard ratio 3.65 [1.98-6.72]) and the need for surgical
      intervention (hazard ratio 2.86 [1.19-6.88]). Thus, our study defines a set of X
      ray variables that predict functional PD catheter problems and can be used for
      troubleshooting in individual cases as well as for education and internal audit
      purposes. 

PMID- 24940800
TI  - SUMOylation determines turnover and localization of nephrin at the plasma
      membrane.
AB  - Podocyte effacement and the reformation of foot processes and slit diaphragms can
      be induced within minutes experimentally. Therefore, it seems likely that the
      slit diaphragm proteins underlie orchestrated recycling mechanisms under the
      control of posttranslational modifiers. One of these modifiers, SUMO (small
      ubiquitin-like modifier), is an ubiquitin-like protein with a 20% corresponding
      identity to ubiquitin. Modification by SUMOs to proteins on lysine residues can
      block the ubiquitination of the same site leading to the stabilization of the
      target protein. Here we found in vitro and in vivo that nephrin is a substrate
      modified by SUMO proteins thereby increasing its steady-state level and
      expression at the plasma membrane. A conversion of lysines to arginines at
      positions 1114 and 1224 of the intracellular tail of murine nephrin led to
      decreased stability of nephrin, decreased expression at the plasma membrane, and
      decreased PI3K/AKT signaling. Furthermore, treatment of podocytes with the
      SUMOylation inhibitor ginkgolic acid led to reduced membrane expression of
      nephrin. Similarly, the conversion of lysine to arginine at position 1100 of
      human nephrin caused decreased stability and expression at the plasma membrane.
      As SUMOylation is a reversible process, our results suggest that SUMOylation
      participates in the tight orchestration of nephrin turnover at the slit
      diaphragm. 

PMID- 24940802
TI  - The calcium-binding protein complex S100A8/A9 has a crucial role in controlling
      macrophage-mediated renal repair following ischemia/reperfusion.
AB  - Upon ischemia/reperfusion (I/R)-induced injury, several damage-associated
      molecular patterns are expressed including the calcium-binding protein S100A8/A9
      complex. S100A8/A9 can be recognized by Toll-like receptor-4 and its activation
      is known to deleteriously contribute to renal I/R-induced injury. To further test
      this, wild-type and S100A9 knockout mice (deficient for S100A8/A9 complex) were
      subjected to renal I/R. The expression of S100A8/A9 was significantly increased 1
      day after I/R and was co-localized with Ly6G (mouse neutrophil marker)-positive
      cells. These knockout mice displayed similar renal dysfunction and damage and
      neutrophil influx compared with wild-type mice at this early time point.
      Interestingly, S100A9 knockout mice displayed altered tissue repair 5 and 10 days
      post I/R, as reflected by increased renal damage, sustained inflammation,
      induction of fibrosis, and increased expression of collagens. This coincided with
      enhanced expression of alternatively activated macrophage (M2) markers, while the
      expression of classically activated macrophage (M1) markers was comparable.
      Similarly, S100A9 deficiency affected M2, but not M1 macrophage polarization in
      vitro. During the repair phase following acute kidney injury, S100A9 deficiency
      affects M2 macrophages in mice leading to renal fibrosis and damage. Thus,
      S100A8/A9 plays a crucial part in controlling macrophage-mediated renal repair
      following I/R. 

PMID- 24940801
TI  - Discovery of new glomerular disease-relevant genes by translational profiling of
      podocytes in vivo.
AB  - Identifying new biomarkers and therapeutic targets for podocytopathies such as
      focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of
      transcriptional changes in podocytes over the course of disease. Here we used
      translating ribosome affinity purification (TRAP) to isolate and profile podocyte
      specific mRNA in two different models of FSGS. We expressed enhanced green
      fluorescent protein-tagged to ribosomal protein L10a in podocytes under the
      control of the collagen-1alpha1 promoter, enabling one-step podocyte-specific
      mRNA isolation over the course of disease. This TRAP protocol robustly enriched
      known podocyte-specific mRNAs. We crossed Col1alpha1-eGFP-L10a mice with the
      Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte
      transcriptional profiles at 2, 6, and 44 weeks of age. Two upregulated podocyte
      genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein
      level in biopsies from patients with FSGS, validating this approach. There was no
      dilution of podocyte-specific transcripts during disease. These are the first
      podocyte-specific RNA expression data sets during aging and in two models of
      FSGS. This approach identified new podocyte proteins that are upregulated in FSGS
      and defines novel biomarkers and therapeutic targets for human glomerular
      disease. 

PMID- 24940803
TI  - Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23
      transcription.
AB  - Parathyroid hormone (PTH) increases FGF23 mRNA and protein levels in vivo and in
      vitro. Here we tested whether the increased FGF23 expression by PTH is mediated
      by the orphan nuclear receptor Nurr1. PTH increased Nurr1 mRNA levels prior to
      elevation of FGF23 mRNA levels in UMR-106 rat osteoblast-like cells. Activation
      of PKA increased both FGF23 and Nurr1 mRNA levels. Modification of Nurr1
      expression showed that Nurr1 is essential for the PTH-mediated increase in FGF23
      and luciferase reporter gene experiments identified a functional promoter region
      containing several potential Nurr1 binding sites. Chromatin immunoprecipitation
      assays confirmed the binding of Nurr1 to these regions in the FGF23 promoter. In
      vivo, Nurr1 mRNA and protein levels were increased in calvaria from rats with
      experimental CKD together with high PTH and FGF23 expression. Calcimimetics
      decrease PTH and FGF23 levels in CKD patients. Importantly, in rats with
      experimental CKD, the calcimimetic R568 decreased PTH expression, calvaria Nurr1
      mRNA and protein levels, and FGF23 mRNA. Immunohistochemistry for Nurr1 showed an
      increase in the number of Nurr1 expressing osteocytes in the femurs of rats with
      CKD and this was decreased by R568. Thus, the effect of PTH to increase FGF23
      transcription is mediated by Nurr1 in vitro and in vivo. In CKD, calcimimetics
      decrease PTH, which in turn decreases Nurr1 and consequently FGF23. 

PMID- 24940804
TI  - High-mobility group box 1 is a novel deacetylation target of Sirtuin1.
AB  - High-mobility group box 1 (HMGB1) undergoes acetylation, nuclear-to-cytoplasmic
      translocation, and release from stressed kidneys, unleashing a signaling cascade
      of events leading to systemic inflammation. Here, we tested whether the
      deacetylase activity of Sirtuin1 (SIRT1) participates in regulating nuclear
      retention of HMGB1 to ultimately modulate damage signaling initiated by HMGB1
      secretion during stress. When immunoprecipitated acetylated HMGB1 was incubated
      with SIRT1, HMGB1 acetylation decreased by 57%. Proteomic analysis showed that
      SIRT1 deacetylates HMGB1 at four lysine residues (55, 88, 90, and 177) within the
      proinflammatory and nuclear localization signal domains of HMGB1. Genetic
      ablation or pharmacological inhibition of SIRT1 in endothelial cells increased
      HMGB1 acetylation and translocation. In vivo, deletion of SIRT1 reduced nuclear
      HMGB1 while increasing its acetylation and release into circulation during basal
      and ischemic conditions, causing increased renal damage. Conversely, resveratrol
      pretreatment led to decreased HMGB1 acetylation, its nuclear retention, decreased
      systemic release, and reduced tubular damage. Thus, a vicious cycle is set into
      motion in which the inflammation-induced repression of SIRT1 disables
      deacetylation of HMGB1, facilitates its nuclear-to-cytoplasmic translocation, and
      systemic release, thereby maintaining inflammation. 

PMID- 24940805
TI  - Ofloxacin resistance in Mycobacterium tuberculosis is associated with efflux pump
      activity independent of resistance pattern and genotype.
AB  - Drug-resistance to ofloxacin (OFX) in Mycobacterium tuberculosis is due to
      missense mutations in gyrA and other factors, such as alterations in the activity
      of drug efflux pumps. In this study, we identified 8 extensively drug resistant
      tuberculosis (XDR-TB), 40 multidrug resistant TB (MDR-TB), 38 polydrug resistant
      TB (PDR-TB), and 16 single OFX-resistant TB from 102 clinical isolates. We tested
      the effect of three efflux inhibitors, reserpine, verapamil, and carbonyl cyanide
      m-chlorophenyl hydrazone (CCCP), on changes in the OFX minimum inhibitory
      concentration (MIC) using Resazurin microtitre assay. These three inhibitors
      changed the MICs from 2- to 32-fold, with CCCP having the strongest effect. A
      total of 55%, 74%, and 83% of the tested isolates had changes in MIC of more than
      two-fold by reserpine, verapamil, and CCCP, respectively. The inhibitors led to
      similar fold-changes of OFX MICs in the XDR, MDR, PDR, and single OFX-resistant
      isolates. For each inhibitor, a higher resistance to OFX was associated with the
      greater efflux pump activity. There were no significant differences in the effect
      of efflux pump inhibitors upon Beijing and non-Beijing M. tuberculosis genotypes.
      Taken together, these results indicate that the efflux pump activity was greater
      in the isolates higher resistant to OFX and had similar effects on isolates with
      different drug resistant pattern, and had similar effects on Beijing and non
      Beijing genotypes. 

PMID- 24940807
TI  - Characterization of primary and permanent teeth using terahertz spectroscopy.
AB  - OBJECTIVES: To analyse teeth samples by using terahertz time-domain spectroscopy
      (THz-TDS) system that was developed in the laboratory to measure the properties
      of sliced teeth sections in transmission mode. METHODS: Using home-built THz-TDS
      system, we analysed a total of 25 teeth samples (9 primary and 16 permanent
      teeth). For transmission measurements, the refractive index and absorptive
      properties of the teeth sections were calculated. Difference between groups was
      tested using Mann-Whitney U-test statistics at the specific frequency of 0.5 THz,
      which was at the midpoint of the bandwidth. Median and minimum-maximum values
      were given as descriptive statistics. Type-I error rate was taken as alpha =
      0.05. RESULTS: Median refractive index values for permanent and primary teeth
      were found to be 2.53 and 2.54, respectively. Median absorption coefficient
      values for permanent and primary teeth were found to be 26.29 and 29.67,
      respectively. Median refractive index values for both healthy and carious teeth
      were found to be 2.54. Median absorption coefficient values for healthy and
      carious teeth were found to be 26.52 and 27.13, respectively. Although higher
      median absorption coefficient values were found for primary and carious teeth
      than those of permanent and healthy teeth, the differences were insignificant (p
      > 0.05). In addition, no statistical differences were found for refractive index
      values among different groups (p > 0.05). CONCLUSIONS: THz imaging has the
      potential to be used in assessing dental structures.

PMID- 24940806
TI  - An unusual case of intraosseous vascular malformation of the maxilla mimicking
      fibrous dysplasia: a case report and literature review on imaging features of
      intraosseous vascular anomalies of the jaw.
AB  - Intraosseous vascular malformation (IVM) is a relatively rare pathological
      condition that may pose significant risks, such as excessive bleeding, during
      surgical procedures. We present a case of an 18-year-old female patient with firm
      swelling in the left maxilla. A bony expansion over the left half of the maxilla
      with preservation of the outer cortex and a ground glass appearance on CT images
      initially revealed a possibility of fibrous dysplasia. However, a tentative
      diagnosis of IVM was made based on the vascular nature of the lesion as well as
      the patient's surgical history and additional imaging findings. IVM should be
      included in the differential diagnosis of an expansile bony lesion with
      trabecular alteration. Through the literature review, it was found that imaging
      findings, such as a neurovascular canal widening on CT images and a hyperintense
      signal on T1 weighted MR images, might be helpful in differentiating IVM from
      other pathologies. 

PMID- 24940809
TI  - Staging and risk factors of chronic kidney disease of outpatients in Shanghai.
AB  - PURPOSE: We conducted a survey to determine the stages distribution of chronic
      kidney disease (CKD) using estimated glomerular filtration rate (eGFR) Study
      Equation and evaluate the risk factors for these patients. METHODS: All
      participants completed a questionnaire documenting their social demographic
      status, personal and family medical history and lifestyle behaviors. Blood and
      urine samples were collected for laboratory testing. The Chi-square test/analysis
      of variance and multiple/logistic regression were applied for data analysis.
      There were 530 CKD patients enrolled in this survey. RESULTS: The Chi-square
      analysis showed that there was significant difference among different CKD stages
      in age, gender, BMI (body mass index), medical insurance and education status.
      Five factors (age, gender, BMI, hypertension, and hyperuricemia) were associated
      with decreased kidney function (eGFR<60 mL/min/1.73 m(2)). Five factors (age >=
      65 years, hypertension, proteinuria, hematuria, and hyperuricemia) were
      associated with abnormal kidney function (eGFR<90 mL/min/1.73 m(2)). Three
      factors (low education status, hypertension, and proteinuria) were associated
      with kidney failure (eGFR<15 mL/min/1.73 m(2)). CONCLUSIONS: Older patients,
      female with higher BMI, proteinuria and hyperuricemia, complicating with
      hypertension and diabetes tend to be easier for CKD progression. However,
      patients with higher education have the lower risk of progressing to end-stage
      renal disease.

PMID- 24940808
TI  - Characteristic features of the adenomatoid odontogenic tumour on cone beam CT.
AB  - OBJECTIVES: To illustrate characteristic features of adenomatoid odontogenic
      tumour (AOT) on CBCT. METHODS: The archived CBCT and panoramic radiographs of
      eight patients histopathologically diagnosed as AOT were analysed. The
      radiographic features displayed on both radiographic images were carefully
      described and compared. RESULTS: All eight AOT cases presented as unilocular and
      well-demarcated lesions on both CBCT and panoramic images. CBCT images displayed
      three-dimensional interpretation of AOT lesions, especially the detailed
      intralesional radiopacities. Numerous discrete radiopaque foci scattered in the
      lesion with evident contrast to the radiolucent background could be considered as
      one of the characteristic features of AOT on CBCT. CONCLUSIONS: Compared with
      panoramic radiography, CBCT seems to possess better potential in diagnosing AOT.

PMID- 24940810
TI  - The discovery of spectral opponency in visual systems and its impact on
      understanding the neurobiology of color vision.
AB  - The two principal theories of color vision that emerged in the nineteenth century
      offered alternative ideas about the nature of the biological mechanisms that
      underlie the percepts of color. One, the Young-Helmholtz theory, proposed that
      the visual system contained three component mechanisms whose individual
      activations were linked to the perception of three principal hues; the other, the
      Hering theory, assumed there were three underlying mechanisms, each comprising a
      linked opponency that supported contrasting and mutually exclusive color
      percepts. These competing conceptions remained effectively untested until the
      middle of the twentieth century when single-unit electrophysiology emerged as a
      tool allowing a direct examination of links between spectral stimulation of the
      eye and responses of individual cells in visual systems. This approach revealed
      that the visual systems of animals known to have color vision contain cells that
      respond in a spectrally-opponent manner, firing to some wavelengths of
      stimulation and inhibiting to others. The discovery of spectral opponency, and
      the research it stimulated, changed irrevocably our understanding of the biology
      of color vision. 

PMID- 24940811
TI  - Regret causes ego-depletion and finding benefits in the regrettable events
      alleviates ego-depletion.
AB  - This study tested the hypotheses that experiencing regret would result in ego
      depletion, while finding benefits (i.e., "silver linings") in the regret
      eliciting events counteracted the ego-depletion effect. Using a modified gambling
      paradigm (Experiments 1, 2, and 4) and a retrospective method (Experiments 3 and
      5), five experiments were conducted to induce regret. Results revealed that
      experiencing regret undermined performance on subsequent tasks, including a paper
      and-pencil calculation task (Experiment 1), a Stroop task (Experiment 2), and a
      mental arithmetic task (Experiment 3). Furthermore, finding benefits in the
      regret-eliciting events improved subsequent performance (Experiments 4 and 5),
      and this improvement was mediated by participants' perceived vitality (Experiment
      4). This study extended the depletion model of self-regulation by considering
      emotions with self-conscious components (in our case, regret). Moreover, it
      provided a comprehensive understanding of how people felt and performed after
      experiencing regret and after finding benefits in the events that caused the
      regret.

PMID- 24940812
TI  - Patterns of responding on a balloon analogue task reveal individual differences
      in overall risk-taking: choice between guaranteed and uncertain cash.
AB  - We explored the utility of analyzing within- and between-balloon response
      patterns on a balloon analogue task (BAT) in relation to overall risk scores, and
      to a choice between a small guaranteed cash reward and an uncertain reward of the
      same expected value. Young adults (n = 61) played a BAT, and then were offered a
      choice between $5 in cash and betting to win $0 to $15. Between groups, pumping
      was differentially influenced by explosions and by the number of successive
      unexploded balloons, with risk takers responding increasingly on successive
      balloons after an explosion. Within-balloons, risk takers showed a characteristic
      pattern of constant high rate, while non-risk takers showed a characteristic
      variable lower rate. Overall, results show that the higher number of pumps and
      explosions that characterize risk takers at a molar level, result from particular
      forms of adaptation to the positive and negative outcomes of choices seen at a
      molecular level.

PMID- 24940813
TI  - Effects of early maternal separation on subsequent reproductive and behavioral
      outcomes in male rats.
AB  - To investigate effects of maternal separation on reproductive and behavioral
      outcomes, male Wistar rats were separated from their mothers daily for 3 hr
      (maternal separation; MS) or 0 hr (control) from postnatal day (PND) 1 to 14.
      Timing of puberty, reproductive parameters, hormone levels, and aggressive
      behaviors in juvenile and adult rats were examined. Contrary to expectations,
      there was no effect of maternal separation on any measure of aggression. However,
      maternal separation altered peripubertal testosterone secretion and increased
      mean day of preputial separation. In addition, adult MS males demonstrated less
      total sexual behavior. There was no difference in sperm counts or testosterone
      levels at necropsy on PND 56 or in adulthood, but seminal vesicle weights were
      increased in adult MS rats. These results suggest that early life stress may
      influence hypothalamic-pituitary-gonadal axis development in males, at least
      during peripuberty.

PMID- 24940814
TI  - Relationship between academic motivation and mathematics achievement among Indian
      adolescents in Canada and India.
AB  - This study examined the relationships between academic motivation-intrinsic
      motivation, extrinsic motivation, amotivation-and mathematics achievement among
      363 Indian adolescents in India and 355 Indian immigrant adolescents in Canada.
      Results of hierarchical multiple regression analyses showed that intrinsic
      motivation, extrinsic motivation, and amotivation were not statistically
      significantly related to mathematics achievement among Indian adolescents in
      India. In contrast, both intrinsic motivation and extrinsic motivation were
      statistically significantly related to mathematics achievement among Indian
      immigrant adolescents in Canada. While intrinsic motivation was a statistically
      significant positive predictor of mathematics achievement among Indian immigrant
      adolescents in Canada, extrinsic motivation was a statistically significant
      negative predictor of mathematics achievement among Indian immigrant adolescents
      in Canada. Amotivation was not statistically significantly related to mathematics
      achievement among Indian immigrant adolescents in Canada. Implications of the
      findings for pedagogy and practice are discussed.

PMID- 24940815
TI  - What looks like sexism and why? The effect of comment type and perpetrator type
      on women's perceptions of sexism.
AB  - Sexist comments are not perceived equally in the eyes of women. We extend
      previous research by examining the degree to which multiple types of potentially
      sexist comments made by multiple types of men are perceived as sexist. Further,
      we examine the degree to which three possible mediators--prototypicality,
      perceived intent, and interdependence--explained these effects. Female
      undergraduate students (N = 248) were randomly assigned to read a scenario in
      which a hostile sexist, benevolent sexist, or objectifying comment was made by
      one of three types of men: a stranger, their boss, or their boyfriend. Results
      demonstrate that hostile sexism was perceived as more sexist than benevolent
      sexism or objectification. Comments made by boyfriends were also rated as less
      sexist than those made by bosses or strangers. Furthermore, perceptions of
      prototypicality of the comment or perpetrator and perceived intent to harm
      mediated the effect of study manipulations on perceptions of sexism.

PMID- 24940816
TI  - Vicariously learned helplessness: the role of perceived dominance and prestige of
      a model.
AB  - Prior research has examined the relationship between various model
      characteristics (e.g., age, competence, similarity) and the likelihood that the
      observers will experience vicariously learned helplessness. However, no research
      in this area has investigated dominance as a relevant model characteristic. This
      study explored whether the vicarious acquisition of learned helplessness could be
      mediated by the perceived dominance of a model. Participants observed a model
      attempting to solve anagrams. Across participant groups, the model displayed
      either dominant or nondominant characteristics and was either successful or
      unsuccessful at solving the anagrams. The characteristics displayed by the model
      significantly affected observers' ratings of his dominance and prestige. After
      viewing the model, participants attempted to solve 40 anagrams. When the dominant
      model was successful, observers solved significantly more anagrams than when he
      was unsuccessful. This effect was not found when the model was nondominant.

PMID- 24940819
TI  - Biomass derived furfural-based facile synthesis of protected (2S)-phenyl-3
      piperidone, a common intermediate for many drugs.
AB  - An efficient synthetic route towards tosyl-protected (2S)-phenyl-3-piperidone, a
      common intermediate for many drugs, has been developed in 5 steps in 54% yield
      from biomass derived furfural. The synthetic utility of the piperidone core
      structure was demonstrated with the synthesis of a NK1 receptor antagonist. 

PMID- 24940817
TI  - Anti-tumor effects of flavonoids from the ethnic medicine Docynia delavayi
      (Franch.) Schneid. and its possible mechanism.
AB  - This study investigated the active components and the anti-tumor efficacy and
      mechanisms of the flavonoids from Docynia delavayi (Franch.) Schneid. (DDS). MTT
      assay was used to examine the growth inhibitory effects of the four flavonoids,
      including chrysin, quercetin, naringenin, and avicularin that were isolated from
      the rhizome of DDS, on human hematomas cell (HepG2), esophageal carcinoma cell
      (EC109), human cervical adenocarcinoma cell (Hela), human colon adenocarcinoma
      cell (SW480), and African green monkey kidney cell (Vero cells). The anti-tumor
      mechanism of chrysin on HepG2 was further investigated by the methods of
      fluorescence staining, flow cytometry, and immunoblotting. The results showed
      that the inhibitory activity of chrysin was much stronger than the other three
      flavonoids on HepG2, EC109, Hela, and SW480 cells for 48 h treatment in vitro.
      Moreover, no inhibiting effect of chrysin on the proliferation of normal cells
      (Vero cells) was observed. Further study revealed that chrysin caused HepG2 cell
      shrinkage, membrane blebbing, and apoptotic body formation, all of which were
      typical characteristics of apoptosis programmed cell death. Flow cytometric
      analysis demonstrated that chrysin increased the sub G0/G1 population, which
      indicated the increased cell apoptosis, thus preventing cells from entering the S
      phase as the population in G2/M or S phase declined; whereas in G0/G1 phase, it
      increased. In addition, immunoblot results showed that chrysin significantly
      increased the expression levels of caspase-3 and Bax proteins, and it decreased
      the expression level of B-cell lymphoma/leukemia-2 (Bcl-2) protein. These
      findings indicate that chrysin is the major flavonoid present in DDS, and it
      induces HepG2 cell death via apoptosis, probably through the participation of
      caspase-3, Bax, and Bcl-2 proteins.

PMID- 24940820
TI  - Chemotherapy alone or HSCT after reduced-intensity conditioning for patients with
      malignant hematologic diseases are not associated to metabolic syndrome: a cross
      sectional observational study.
AB  - The relationship between treatment for hematologic malignancies and risk of
      developing metabolic syndrome (MS) is controversial; in addition, metabolic
      changes following hematopoietic stem cell transplantation (HSCT) is an area of
      growing interest. We documented the presence of MS in patients with hematological
      malignancies treated with chemotherapy and HSCT. Nutritional status,
      anthropometrics, and pertinent laboratory parameters were used to evaluate the
      presence of MS using the Adult Treatment Panel (ATP III) criteria. In the study,
      115 patients were included. Using ATP III criteria, MS was identified in 42
      (44.7%) patients treated only with chemotherapy and in 8 (33.3%) patients with an
      HSCT. There was an important but not significant difference in the mean fasting
      glucose, which was higher in the chemotherapy group (108.32 +/- 54.28 vs. 94.48
      +/- 18.25, P = 0.300). Mean values of biochemical markers and blood pressure were
      not different between the groups. An increase in central obesity in men with
      hematological diseases in comparison to the rest of the population was also found
      (46.7% vs 32.4%). There was no difference in the prevalence of MS between
      patients with hematologic malignancies receiving an HSCT and those treated with
      chemotherapy alone. 

PMID- 24940822
TI  - Tuning of the HOMO-LUMO gap of donor-substituted symmetrical and unsymmetrical
      benzothiadiazoles.
AB  - This article reports the design and synthesis of donor-substituted symmetrical
      and unsymmetrical benzothiadiazoles (BTDs) of 5-12 type D-pi-A-D, D1-pi-A-D2, D1
      A1-A2-D2, D-A1-A2-D and D-A1-A2-A1-D by Ullmann, Suzuki and cycloaddition
      retroelectrocyclization reactions. The photophysical, electrochemical and
      computational properties were studied and show substantial donor-acceptor
      interaction. Their single photon absorption show strong charge transfer bands in
      the near-infrared (NIR) region and the electrochemical reduction show multiple
      reduction waves. The optical HOMO-LUMO gap of BTDs 5-12 was found to be a
      function of the number and nature of the acceptors. Computational studies reveal
      that strong cyano-based acceptors, dicyanoquinodimethane (DCNQ) and
      tetracyanobutadiene (TCBD) lower the LUMO level in BTDs 7-12, which results in a
      low HOMO-LUMO gap compared to acetylene linked BTDs 5 and 6. The BTDs with
      carbazole and single TCBD and DCNQ acceptors show better thermal stability.

PMID- 24940821
TI  - Taming the oxidative power of SeO(3) in 1,4-dioxane, isolation of two new isomers
      of mixed-valence selenium oxides, and two unprecedented cyclic esters of selenic
      acid.
AB  - The reaction of (SeO3)4 with 1,4-dioxane (diox, dioxane) with or without diluting
      solvent led to the isolation of the unprecedented esters of selenic acid-1,2
      ethyl selenate (CH2O)2SeO2 and the glyoxal diselenate O2Se[(OCHO)2]SeO2. It was
      possible to isolate an unknown dimeric form of Se2O5 (Se4O10.(diox)2) and a
      geometrical isomer of the mixed-valence oxide trans-Se3O7, both stabilized by
      dioxane. The dioxane adduct of monomeric selenium trioxide SeO3.diox was obtained
      from the reaction of (SeO3)4 with dioxane in liquid SO2. The reaction mechanism
      for the formation of these compounds was elucidated, and the molecular structure
      of the unstable form of the selenium trioxide was determined, consisting in a
      trimeric arrangement (SeO3)3. 

PMID- 24940823
TI  - The role of capsule endoscopy in the evaluation and treatment of obscure-overt
      gastrointestinal bleeding during daily clinical practice: a prospective
      multicenter study.
AB  - OBJECTIVE: Capsule endoscopy (CE) is most commonly performed to evaluate obscure
      gastrointestinal bleeding (GIB). However, at present the role of CE in patients
      with obscure-overt GIB especially during daily clinical practice is unknown. The
      aim of the present study was to investigate the diagnostic yield and the impact
      of CE on the management of patients with obscure-overt GIB. MATERIAL AND METHODS:
      Between January 2007 and December 2011 we prospectively included all patients
      with obscure-overt GIB who underwent CE after negative bidirectional endoscopy.
      CE findings revealing the cause of bleeding, type of therapeutic intervention and
      clinical variables associated with positive CE and recurrence of GIB were
      evaluated. RESULTS: One hundred and eighteen patients with a median age of 66
      years (range 8-89 years) were enrolled in the final analysis. The overall
      diagnostic yield of the CE was 66.9%. The most common findings were
      angiodysplasias (33.1%), followed by ulcer (23.7%), and tumors (6.8%). Age (p =
      0.001) and cardiovascular disease (p = 0.007) were significant clinical variables
      predicting the higher incidence of angiodysplasias. Specific therapeutic
      interventions were undertaken in 54 patients with positive CE (68.4%). Recurrence
      of GIB was observed in one patient with negative CE (2.6%) and 16 patients with
      positive CE (20.3%). Univariate and multivariate analysis showed high age and no
      therapeutic intervention as significant factors associated with recurrent
      bleeding. CONCLUSIONS: CE represents a promising diagnostic method in the
      investigation of obscure-overt GIB, with significant impact on its clinical
      management in daily clinical practice.

PMID- 24940824
TI  - Matrix-assisted ionization vacuum for high-resolution Fourier transform ion
      cyclotron resonance mass spectrometers.
AB  - Matrix-assisted ionization vacuum (MAIV) produces charge states similar to
      electrospray ionization (ESI) from the solid state without requiring high voltage
      or added heat. MAIV differs from matrix-assisted laser desorption/ionization
      (MALDI) in that no laser is needed and abundant multiply charged ions are
      produced from molecules having multiple basic sites such as proteins. Here we
      introduce simple modifications to the commercial vacuum MALDI and ESI sources of
      a 9.4 T Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer to
      perform MAIV from both intermediate and atmospheric pressure. The multiply
      charged ions are shown for the proteins bovine insulin, ubiquitin, and lysozyme
      using 3-nitrobenzonitrile as matrix. These are the first examples of MAIV
      operating at pressures as low as 10(-6) mbar in an FT-ICR mass spectrometer
      source, and the expected mass resolving power of 100000 to 400000 is achieved.
      Identical protein charge states are observed with and without laser ablation
      indicating minimal, if any, role of photochemical ionization for the compounds
      studied. 

PMID- 24940825
TI  - Standardized modulation of the injection site allows for insulin dose reduction
      without deterioration of metabolic control.
AB  - OBJECTIVES: Use of an injection site modulation device (InsuPad) in intensive
      insulin treatment reduces frequency of hypoglycemia and prandial insulin
      requirements by enhancing subcutaneous microcirculation. This meal tolerance test
      (MTT) investigation was performed as a sub-study during the real-world BARMER
      study to demonstrate non-inferiority of the reduced insulin doses observed in
      this study with respect to metabolic control. METHODS: The MTT was performed at
      baseline and after 3 months in insulin treated diabetes patients using the
      modulation device vs. a control group without device. The dose used for the MTT
      was individually calculated based on the prandial insulin records from the
      patient diaries before the test. Blood was drawn for determination of glucose,
      insulin, C-peptide, proinsulin, triglycerides, free fatty acids, nitrotyrosine,
      and asymmetric dimethyl-arginine (ADMA) at multiple time-points from 0 to 300
      min. A total of 32 patients from one site were included into this MTT study (8
      female, 7 type 1 diabetes, age: 49.9 +/- 12.5 yrs, HbA1c: 7.2 +/- 0.5%). RESULTS:
      During the BARMER study, mean HbA1c was treated to target (<6.5%) in both groups.
      The prandial insulin dose decreased in the MTT modulation device group by -17.1%,
      but remained unchanged in the control group (-0.1%, p < 0.001). No change was
      seen for the basal insulin dose in both treatment arms. There were no differences
      between the groups with respect to the postprandial curves for glucose, C
      peptide, intact proinsulin, free fatty acids, and triglycerides. Insulin
      absorption was faster with the modulation device (Tmax: 60 +/- 28 min vs. 99 +/-
      46 min, p < 0.05). Key limitations are the small patient sample size and
      impossibility to determine the short-term effects of device use. CONCLUSIONS: The
      results of this meal tolerance sub-study confirm that the observed prandial
      insulin dose reduction when using the injection site modulation device has no
      negative impact on postprandial metabolism.

PMID- 24940826
TI  - The influence of female gender on cardiac arrest outcomes: a systematic review of
      the literature.
AB  - BACKGROUND: Sudden cardiac arrest is an important cause of cardiovascular
      mortality. The impact of gender on the outcome of cardiac arrest is not clear and
      data about that is limited. OBJECTIVE: Understanding the influence of gender on
      cardiac arrest through a systematic review of the published literature. METHODS:
      A search of all published studies in English between January 1970 and May 2013
      was performed using the electronic databases PubMed and MEDLINE, using the key
      words 'cardiac arrest', 'outcome', and 'gender'. RESULTS: Eleven studies were
      included in this review, all of which were observational studies conducted using
      national-based database registries of cardiac arrest. A total of 548,440 patients
      were enrolled in these studies with 220,646 (40.3%) of them being female
      patients. In general, there was a lower percentage of women in the reported
      studies compared to men. Women were older in age and more likely to have non
      shockable rhythms as the initial rhythm. Women also had a lower rate of witnessed
      arrest, a lower rate of bystander resuscitation, a higher rate of survival until
      hospital admission and a lower rate of in-hospital survival compared to men.
      Women also had a more favorable one month survival and neurological outcome.
      CONCLUSION: In the reported literature female gender seems to offer survival and
      outcome advantages following out-of-hospital cardiac arrest over male gender.
      This is in contrast to most other aspects of heart disease in which women tend to
      have a worse prognosis.

PMID- 24940827
TI  - Metabolomic Profiling of Autoimmune Hepatitis: The Diagnostic Utility of Nuclear
      Magnetic Resonance Spectroscopy.
AB  - Autoimmune hepatitis (AIH) is often confused with other liver diseases because of
      their shared nonspecific symptoms and serological and histological overlap. This
      study compared the plasma metabolomic profiles of patients with AIH, primary
      biliary cirrhosis (PBC), PBC/AIH overlap syndrome (OS), and drug-induced liver
      injury (DILI) with those of healthy subjects to identify potential biomarkers of
      AIH. Metabolomic profiling and biomarker screening were performed using proton
      nuclear magnetic resonance spectroscopy (1H NMR) coupled with a partial least
      squares discriminant analysis. Compared with the levels in healthy volunteers and
      other liver disease patients, AIH patients exhibited relatively high levels of
      plasma pyruvate, lactate, acetate, acetoacetate, and glucose. Such metabolites
      are typically related to energy metabolism alterations and may be a sign of
      metabolic conversion to the aerobic glycolysis phenotype of excessive immune
      activation. Increased aromatic amino acids and decreased branched-chain amino
      acids were found in the plasma of AIH patients. The whole NMR profiles were
      stepwise-reduced, and nine metabolomic biomarkers having the greatest
      significance in the discriminant analysis were obtained. The diagnostic utility
      of the selected metabolites was assessed, and these biomarkers achieved good
      sensitivity, specificity, and accuracy (all above 93%) in distinguishing AIH from
      PBC, DILI, and OS. This report is the first to present the metabolic phenotype of
      AIH and the potential utility of 1H NMR metabolomics in the diagnosis of AIH.

PMID- 24940829
TI  - Editorial.

PMID- 24940830
TI  - Diagnosis and treatment of premenstrual dysphoric disorder.
AB  - Premenstrual syndrome (PMS) is a common problem and patients with PMS are
      encountered by obstetricians, gynecologists, family practitioners, internists
      (general physicians) and psychiatrists. Despite several decades of biological
      research, the etiology of the disorder is still elusive. The introduction of a
      psychiatric category called premenstrual dysphoric disorder (PMDD), describing
      women with severe emotional premenstrual symptoms, has advanced biological
      treatment research by identifying a more homogeneous patient population. This
      paper aims to review our current understanding of the clinical presentation,
      underlying psycho-biology, and essentials of treatment for premenstrual dysphoric
      disorder. 

PMID- 24940831
TI  - The assessment and management of behavioural manifestations of dementia: a review
      and results of a controlled trial.
AB  - Although the cognitive impairments in dementia are the defining aspect, the non
      cognitive changes such as behavioural disturbance and personality change are very
      common and may cause great distress to the patient and the carer. This article
      reviews the definition, prevalence and nature of behavioural disturbance in
      dementia. In addition, we review assessment scales and published reports of
      psychological, physical and psychosocial management strategies. Finally, we
      present the results of a successful randomized controlled trial of an
      individualized intervention package for behavioural manifestations of dementia.
      We conclude that this approach can help alleviate some of the distressing
      symptoms of dementia. 

PMID- 24940828
TI  - Chronic alcohol ingestion in rats alters lung metabolism, promotes lipid
      accumulation, and impairs alveolar macrophage functions.
AB  - Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to
      inflammatory lung diseases, including infectious pneumonia and acute respiratory
      distress syndrome. Although alcoholism has been shown to alter hepatic
      metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis,
      the effects of alcohol on pulmonary metabolism remain largely unknown. Because
      both the lung and the liver actively engage in lipid synthesis, we hypothesized
      that chronic alcoholism would impair pulmonary metabolic homeostasis in ways
      similar to its effects in the liver. We reasoned that perturbations in lipid
      metabolism might contribute to the impaired pulmonary immunity observed in people
      who chronically consume alcohol. We studied the metabolic consequences of chronic
      alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells
      and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion
      significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein
      kinase, increasing lipid synthesis, and suppressing the expression of genes
      essential to metabolizing fatty acids (FAs). Furthermore, we show that these
      metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic
      fatty liver and is characterized by marked accumulation of triglycerides and free
      FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial
      type II cells. We provide evidence that the metabolic alterations in alcohol
      exposed rats are mechanistically linked to immune impairments in the alcoholic
      lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic
      functions and agonist-induced inflammatory responses. In summary, our work
      demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis
      and promotes pulmonary immune dysfunction. These findings suggest that therapies
      aimed at reversing alcohol-related metabolic alterations might be effective for
      preventing and/or treating alcohol-related pulmonary disorders. 

PMID- 24940832
TI  - The pharmacotherapy of post traumatic stress disorder. A literature review and
      case report of treatment with nefazodone.
AB  - Post traumatic stress disorder (PTSD) is a common and serious debilitating
      condition with a host of co-morbid disorders. Research has uncovered a number of
      structural and neurochemical abnormalities that provide exciting insights into
      the mind-body continuum under stress. Increasing efforts are being addressed to
      tailor medication according to a model based on the dysregulation of
      neurotransmitters. Controlled trials of treatment, whilst offering hope, are
      inadequate to permit the development of evidence-based protocols for the
      treatment of PTSD. Further psychopharmacological research is urgently required. 

PMID- 24940833
TI  - Psychiatric disorders and violent behavior.
AB  - Until recently, many researchers have been sceptical about any relationship
      between psychiatric disorders and violence. Since public opinion has always been
      prejudiced against the mentally ill, professionals in the field of psychiatry
      have been very cautious about further stigmatizing individuals with psychiatric
      illnesses. The authors have reviewed studies of mental disorders and violence,
      particularly the most recent, and find that there is increasing evidence for an
      association between psychiatric disorders and violence. Recent data suggest that
      the combination of previous violent behavior, alcoholism and antisocial
      personality disorder markedly increases the risk of future violent behavior.
      Schizophrenia, personality disorders and alcoholism per se do not increase the
      risk of violent behavior as much as do the above factors, but the risk among
      these diagnostic groups is, however, notably higher than that in the general
      population. The authors emphasize that only a minority of patients with mental
      disorders are violent. Future research is needed to better identify and treat
      these potentially violent patients. 

PMID- 24940834
TI  - Psycho-oncology and the role of the psychiatrist in cancer patient care.
AB  - Cancer and its treatment lead to emotional distress for most patients and their
      families, and to psychiatric illness for some. Psychiatrists can contribute to
      the prevention, recognition and treatment of these problems. Educational and
      supportive group work, for both patients and staff, complements the assessment
      and management of individually referred cases. Psychiatrists in this setting
      require a good understanding of medical matters, and good working relationships
      with colleagues both in cancer services and mental health services. The nature of
      the clinical work will be illustrated by case vignettes. 

PMID- 24940835
TI  - EPOS: Increasing our understanding of the treatment of schizophrenia; Start of a
      prospective referenced cohort study of sertindole in clinical practice.
AB  - Sertindole is a new limbic-selective antipsychotic agent which has recently
      received marketing authorization in several countries across Europe for the
      treatment of schizophrenia. The experience gained in around 2200 patients treated
      with sertindole in controlled clinical trials has enabled optimal targeting of
      sertindole to those patient groups who will benefit most and who are least likely
      to experience adverse effects. Ultimately, it is how a new medicinal product is
      used in clinical practice, how it performs in everyday life, and how the patient
      who takes it feels and functions that determine the real benefit/risk ratio of a
      new medicinal product. The European Post-marketing Observational Serdolect(r)
      project (EPOS) is a post-marketing, referenced, observational, cohort, safety
      study in the treatment of schizophrenic patients initiated earlier this year. It
      is planned to recruit over 12 000 patients in two cohorts in centres throughout
      Europe. The aims are to provide a full safety evaluation of sertindole under
      marketed conditions at the relevant clinical dosage, and further, to provide
      epidemiological data on schizophrenic patients receiving sertindole or other
      treatment under the usual clinical conditions in Europe. At the moment, the study
      is the only one of its kind to be undertaken in schizophrenia and will provide
      important new data for psychiatrists around the world. 

PMID- 24940836
TI  - Fluoxetine augmentation in bipolar disorder patients on maintenance lithium
      treatment.
AB  - Lithium augmentation during long-term treatment with antidepressants has long
      been considered an effective therapeutic strategy in the treatment of depressive
      syndromes. This paper deals with an 'opposite' strategy, i.e. the use of
      serotonin reuptake inhibitors (SRIs) during maintenance lithium treatment in
      bipolar disorder (BP) patients who may present a breakthrough depressive
      syndrome. The study involved 26 patients on maintenance lithium treatment for a
      mean of 38 months (mean serum lithium level=0.57 mEq/l). Mean fluoxetine dose was
      29.3 mg/day for a mean period of 7.36 weeks. Median HDRS scores before and after
      fluoxetine augmentation were 14 and 6, respectively. The results provide evidence
      for the efficacy of fluoxetine augmentation in the treatment of breakthrough
      depressions occurring in bipolar disorder patients during maintenance lithium
      treatment. The neuropharmacological explanation of the augmentation is not yet
      well understood, but it is conceivable that the improvement of the depressive
      symptoms may be related to the increase in serotonergic function provided by
      combination of the two treatments. 

PMID- 24940837
TI  - The Lubeck General Hospital Study. I: Prevalence of psychiatric disorders in
      medical and surgical inpatients.
AB  - The aim of the Lubeck General Hospital study was to assess the prevalence rates
      of psychiatric disorders in medical and surgical general hospital patients, as
      well as treatment needs. In a cross-sectional study, a total of 400 patients were
      interviewed, 200 each from medical and surgical departments. We used the
      standardized Composite International Diagnostic Interview (CIDI) and, in
      addition, a clinical interview. In the first of two articles, the prevalence
      rates of ICD-10 diagnoses, which had to be present within seven days before the
      interview, are described. Of the total sample, 35.5% of the patients received a
      CIDI diagnosis and 46.8% a clinical diagnosis. The most prominent disorders were
      organic mental disorders (CIDI, 18.3%; clinical, 16.5%), alcoholism (4.5% and
      8.3%), and depression (8.3% and 15.3%). With regard to the spectrum of
      psychiatric diagnoses, no significant differences were found between the medical
      and the surgical sample. When compared to surveys of the general population in
      Germany, the prevalence rates of organic mental disorders, alcoholism and
      adjustment disorders were considerably higher in general hospital patients. 

PMID- 24940838
TI  - Prader-Willi syndrome and acute psychosis.
AB  - Prader-Willi Syndrome (PWS) is a genetically determined disorder, with
      characteristic physical and behavioural phenotypes. We describe a girl with PWS
      who developed a psychotic illness, and summarize the course, treatment and
      outcome. We suggest that the development of a psychotic illness in PWS may be an
      association of disorders that paediatricians and child mental health
      professionals should be aware of, and that the cornerstone of management of this
      kind of case is a multi-professional interdisciplinary approach. Important
      aspects of the assessment process which are occasionally overlooked are
      discussed. 

PMID- 24940839
TI  - A patient who changed my practice.
AB  - The patient described in this paper expressed classical depressive delusions.
      However after her statements of doom she would grin and giggle. The author, as a
      young psychiatrist, assumed that she was not seriously depressed. Shortly
      afterwards the patient drowned herself. In restrospect the baby had been thrown
      out with the bathwater. Doctors may be too ready to assume that the patient is
      making it all up. 

PMID- 24940841
TI  - Experimental study on the effect of ammonia on the phase behavior of
      tetrahydrofuran clathrates.
AB  - Clathrate hydrates, ice-like crystalline compounds in which small guest molecules
      are enclosed inside cages formed by tetrahedrally hydrogen-bonded water
      molecules, are naturally abundant on Earth and are generally expected to exist on
      icy celestial bodies. A prototypical example is Saturn's moon Titan, where
      dissociation of methane clathrates, a major crustal component, could contribute
      significantly to the replenishment of atmospheric methane. Ammonia is an
      important clathrate inhibiting agent that may be present (potentially at high
      concentrations) in Titan's interior. In this study, low-temperature Raman
      experiments are conducted to examine the dissociation point of tetrahydrofuran
      clathrates, an ambient-pressure analogue of methane clathrates, over a wide range
      of ammonia concentrations from 0 to 25 wt %. A phase diagram for the H2O-THF-NH3
      system is generated, showing two main results: (i) ammonia lowers the
      dissociation point of clathrate hydrates to a similar extent compared to the
      melting of water ice and (ii) THF clathrate exhibits a "liquidus-like" behavior
      in the presence of ammonia, with a eutectic temperature of about 203.6 K. As
      temperatures higher than this estimated eutectic are anticipated within Titan's
      icy crust, these results imply that partial dissociation of clathrates can occur
      readily and may contribute to outgassing from the interior. 

PMID- 24940842
TI  - Ge/C nanowires as high-capacity and long-life anode materials for Li-ion
      batteries.
AB  - Germanium-based materials (Ge and GeOx) have recently demonstrated excellent
      lithium-ion storage ability and are being considered as the most promising
      candidates to substitute commercial carbon-based anodes of lithium-ion batteries.
      Nevertheless, practical implementation of Ge-based materials to lithium-ion
      batteries is greatly hampered by the poor cyclability that resulted from the huge
      volume variation during lithiation/delithiation processes. Herein, uniform carbon
      encapsulated Ge and GeOx nanowires were synthesized by a one-step controlled
      pyrolysis of organic-inorganic hybrid GeOx/ethylenediamine (GeOx/EDA) nanowires
      in H2/Ar and Ar atmospheres, respectively. The as-obtained Ge/C and GeOx/C
      nanowires possess well-defined 0D-in-1D morphology and homogeneous carbon
      encapsulation, which exhibit excellent Li storage properties including high
      specific capacities (approximate 1200 and 1000 mA h g(-1) at 0.2C for Ge/C and
      GeOx/C, respectively). The Ge/C nanowires, in particular, demonstrate superior
      rate capability with excellent capacity retention and stability (producing high
      stable discharge capacities of about 770 mA h g(-1) after 500 cycles at 10C),
      making them promising candidates for future electrodes for high-power Li-ion
      batteries. The improved electrochemical performance arises from synergistic
      effects of 0D-in-1D morphology and uniform carbon coating, which could
      effectively accommodate the huge volume change of Ge/GeOx during cycling and
      maintain perfect electrical conductivity throughout the electrode. 

PMID- 24940845
TI  - Diterpenoids from the Chinese liverwort Heteroscyphus tener and their
      antiproliferative effects.
AB  - Four new ent-labdane diterpenoids, heteroscyphins A-D (1-4), and four known
      diterpenoids (5-8) were isolated from the Chinese liverwort Heteroscyphus tener
      (Steph.) Schiffn. The absolute configuration of compound 1 was defined by single
      crystal X-ray diffraction using Cu Kalpha radiation. Cytotoxicity tests revealed
      that compounds 3 and 5 exhibited modest activity against seven cancer cell lines.
      Compound 5 showed inhibitory effects on prostate cancer (PCa) cell proliferation
      but with less inhibition on non-neoplastic prostate epithelial cells. Compound 5
      markedly caused cell growth arrest at the G0/G1 phase and induced cellular
      apoptosis through ROS-mediated DNA damage in PCa cells. 

PMID- 24940846
TI  - Effect of blocking layer to boost photoconversion efficiency in ZnO dye
      sensitized solar cells.
AB  - The effect of a ZnO compact blocking layer (BL) in dye-sensitized solar cells
      (DSSCs) based on ZnO photoanodes is investigated. BL is generated through spray
      deposition onto fluorine-doped tin oxide (FTO) conducting glass before the
      deposition of a ZnO active layer. The functional properties of dye-sensitized
      solar cells (DSSCs) are then investigated as a function of the thickness of the
      BL for two different kinds of ZnO active layer, i.e., hierarchically self
      assembled nanoparticles and microcubes composed of closely packed ZnO sheets.
      Presence of BL leads to the improvement of photoconversion efficiency (PCE), by
      physically insulating the electrolyte and the FTO. This effect increases at
      increasing BL thickness up to around 800 nm, while thicker BL results in reduced
      cell performance. Remarkable increase in Jsc is recorded, which doubles as
      compared to cells without blocking layer, leading to PCE as high as 5.6% in the
      best cell under one sun irradiation (AM 1.5 G, 100 mW cm(-2)). Electrochemical
      impedance spectroscopy (EIS) elucidates the mechanism boosting the functional
      features of the cells with BL, which relies with enhanced chemical capacitance
      together with an almost unchanged recombination resistance, which are reflected
      in an increased electron lifetime. The results foresee a straightforward way to
      significantly improve the performance of ZnO-based DSSCs. 

PMID- 24940847
TI  - Stress on health-related quality of life in older adults: the protective nature
      of mindfulness.
AB  - OBJECTIVES: The current study examined whether the link between stress and health
      related quality of life was buffered by protective factors, namely mindfulness,
      in a sample of middle-aged and older adults. METHODS: In this cross-sectional
      study, 134 healthy, community-dwelling adults (ages 50-85 years) were recruited
      from Dallas, TX. The participants were screened for depressive symptoms and
      severity (using the Patient Health Questionnaire [PHQ-9]). All participants
      completed measures of self-reported health status (i.e. SF36v2: mental and
      physical health composites), life stress (using the Elders Life Stress Inventory
      [ELSI]), and trait mindfulness (i.e. Mindful Attention Awareness Scale). RESULTS:
      Hierarchical regressions (covarying for age, gender, and education) showed that
      life stress was inversely related to physical and mental health. Mindfulness was
      positively related to mental health. The negative effect of life stress on mental
      health was weakened for those individuals with higher levels of trait
      mindfulness. CONCLUSIONS: The results suggest that mindfulness is a powerful,
      adaptive strategy that may protect middle-aged and older adults from the well
      known harmful effects of stress on mental health.

PMID- 24940848
TI  - Photoinduced proton transfer and isomerization in a hydrogen-bonded aromatic azo
      compound: a CASPT2//CASSCF study.
AB  - Intramolecularly hydrogen-bonded aromatic azo compound 1-cyclopropyldiazo-2
      naphthol (CPDNO) exhibits complicated excited-state behaviors, e.g., wavelength
      dependent photoinduced proton transfer and photoproducts. Its photochemistry
      differs from that of common aromatic azo compounds in which cis-trans
      photoisomerization is dominant. To rationalize the intriguing photochemistry of
      CPDNO at the atomic level, we have in this work employed the complete active
      space self-consistent field (CASSCF) and its second-order perturbation (CASPT2)
      methods to explore the S0, S1, and S2 potential-energy profiles relevant to enol
      keto proton transfer and isomerization reactions. It is found that the proton
      transfer along the bright diabatic (1)pipi* potential-energy profile is almost
      barrierless, quickly forming the fluorescent (1)pipi* keto minimum. In this
      process, the dark (1)npi* state is populated via a (1)pipi*/(1)npi* crossing
      point, but the proton transfer on this dark state is suppressed heavily as a
      result of a large barrier. In addition, two deactivation paths that decay the S1
      enol and keto minima to the S0 state, respectively, were uncovered. For the
      former, it is exoenergetic and thereby thermodynamically favorable; for the
      latter, it is a little endothermic (ca. 5 kcal/mol). Both are energetically
      allowable concerning the available total energy. Finally, on the basis of the
      present results, the experimentally observed wavelength-dependent photoproducts
      were explained very well. 

PMID- 24940849
TI  - High-responsivity mid-infrared graphene detectors with antenna-enhanced
      photocarrier generation and collection.
AB  - Graphene is an attractive photoconductive material for optical detection due to
      its broad absorption spectrum and ultrashort response time. However, it remains a
      great challenge to achieve high responsivity in graphene detectors because of
      graphene's weak optical absorption (only 2.3% in the monolayer graphene sheet)
      and short photocarrier lifetime (<1 ps). Here we show that metallic antenna
      structures can be designed to simultaneously improve both light absorption and
      photocarrier collection in graphene detectors. The coupled antennas concentrate
      free space light into the nanoscale deep-subwavelength antenna gaps, where the
      graphene light interaction is greatly enhanced as a result of the ultrahigh
      electric field intensity inside the gap. Meanwhile, the metallic antennas are
      designed to serve as electrodes that collect the generated photocarriers very
      efficiently. We also elucidate the mechanism of photoconductive gain in the
      graphene detectors and demonstrate mid-infrared (mid-IR) antenna-assisted
      graphene detectors at room temperature with more than 200 times enhancement of
      responsivity (~0.4 V/W at lambda0 = 4.45 MUm) compared to devices without
      antennas (<2 mV/W).

PMID- 24940843
TI  - The hematopoietic chemokine CXCL12 promotes integration of human endothelial
      colony forming cell-derived cells into immature vessel networks.
AB  - Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast
      growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic"
      chemokines and cytokines by inducing/upregulating expression of the respective
      chemokine/cytokine receptors. Coculture of human endothelial colony forming cell
      (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2
      for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and
      its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4
      antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced
      vascular tubule formation, an observation recapitulated by delayed AMD3100
      addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did
      demonstrate a dual action. First, over the later stages of the 14-day cocultures,
      AMD3100 delayed tubule organization into maturing vessel networks, resulting in
      enhanced endothelial cell retraction and loss of complexity as defined by live
      cell imaging. Second, at earlier stages of cocultures, we observed that AMD3100
      significantly inhibited the integration of exogenous ECFC-derived cells into
      established, but immature, vascular networks. Comparative proteome profiler array
      analyses of ECFC-derived cells treated with AMD3100 identified changes in
      expression of potential candidate molecules involved in adhesion and/or
      migration. Blocking antibodies to CD31, but not CD146 or CD166, reduced the ECFC
      derived cell integration into these extant vascular networks. Thus, CXCL12 plays
      a key role not only in endothelial cell sensing and guidance, but also in
      promoting the integration of ECFC-derived cells into developing vascular
      networks. 

PMID- 24940850
TI  - Intrinsic autocorrelation time of picoseconds for thermal noise in water.
AB  - Whether thermal noise is colored or white is of fundamental importance. In
      conventional theory, thermal noise is usually treated as white noise so that
      there are no directional transportations in the asymmetrical systems without
      external inputs, since only the colored fluctuations with appropriate
      autocorrelation time length can lead to directional transportations in the
      asymmetrical systems. Here, on the basis of molecular dynamics simulations, we
      show that the autocorrelation time length of thermal noise in water is ~10 ps at
      room temperature, which indicates that thermal noise is not white in the
      molecular scale while thermal noise can be reasonably assumed as white in macro-
      and meso-scale systems. The autocorrelation time length of thermal noise is
      intrinsic, since the value is almost unchanged for different temperature coupling
      methods. Interestingly, the autocorrelation time of thermal noise is correlated
      with the lifetime of hydrogen bonds, suggesting that the finite autocorrelation
      time length of thermal noise mainly comes from the finite lifetime of the
      interactions between neighboring water molecules.

PMID- 24940851
TI  - [Influence of risk-factors in infants on the peculiarities of cognitive
      development].
AB  - The importance of risk-factors during the early development of children on
      development of cognitive difficulties in preschoolers and school children are
      reviewed. The effectiveness of comprehensive diagnostic of main reasons of
      disorders of cognitive development is shown. The importance of complex medical,
      pedagogical, psycho-physiological and neuropsychological treatment of cognitive
      disabilities in children is demonstrated as well. 

PMID- 24940852
TI  - [Some features of development and course of bronchial asthma in children in
      azerbaijan].
AB  - According to the international "ISAAC" program, we studied the peculiarities of
      bronchial asthma in children at the age of 13-14 years, in various climatic and
      geographic regions of Azerbaijan. At the first stage of investigation, 14693
      eighth class pupils of high school from the four various regions were surveyed:
      the I region (n=4979) - an industrial city, placed in a semi-desert area; the II
      region (n=3010) - rural areas, located in a semi-desert climatic zone; the III
      region (n=3133) - areas, located in a subtropical climatic zone; the IV region
      (n=3571) - an ecologically clean mountainous region, located along southern
      slopes of the Greater Caucasian ridge. At the second stage of the investigation
      allergological, clinical-functional examinations were carried out in children
      with symptoms of allergic diseases. It was established that prevalence of BA was
      reliably more frequent in the industrial city (4,6%) than in other three,
      especially rural areas. In subtropical climatic area 2,8%, in rural semi-desert
      area - 2,5%, in mountainous region - 1,8% of examined children were suffering
      from BA. Study of the clinical course of diseases in children with allergic
      diseases and their allergic status revealed that structure and expressiveness of
      sensitization to domestic, pollen, fungous and food allergens depends on residing
      area.

PMID- 24940853
TI  - Cannabis: a controversial 21st-century drug of antiquity.
AB  - Cannabis consumption has been popular for thousands of years and its historical
      use is noted in many parts of the world including ancient China, India, the
      Middle East. It is currently the most popular illicit drug in the world, is being
      utilized as a medicinal plant, and many parts of the world are legalizing this
      drug. This discussion considers various aspects of cannabis use including its
      prevalence, history, co-morbid drug abuse, designer cannabinoids, psychiatric
      adverse effects, medical adverse effects, and management options. The youth of
      the world should be comprehensively taught that cannabis is neither a safe nor a
      benign drug. Prevention with comprehensive drug education is the best plan for
      our youth since management of a chronic or heavy cannabis consummer remains
      difficult and fraught with failure if cessation is the goal. Caveat emptor! 

PMID- 24940854
TI  - Final height, target height and the community.
AB  - Height varies with age, and it varies with historic time. Final height is
      determined by endocrine parameters and genetics, by nutrition and health, by
      environmental factors, by birth weight, early growth, BMI, and developmental
      tempo. European populations of the 19th century were short, but their shortness
      did not result from growth impairment at all ages. In those days, shortness was
      mainly due to a significantly blunted adolescent growth spurt. New modelling
      approaches suggest an independent regulation of adolescent growth and final
      height: the target for growth and final height appears to be set by the
      community. In order to test this hypothesis, we formed a geographic network of
      Switzerland consisting of 169 nodes (district capitals) and 335 connecting edges
      (roads), and investigated military conscript data obtained between 2004 and 2009.
      Average height of Swiss military conscripts was 178.2 cm (SD 6.5 cm). But
      conscripts from first order neighbouring districts were more similar in height
      than expected. Short stature districts have short, tall stature districts have
      tall neighbours. We found significant height correlations between 1st (r=0.58),
      2nd (r=0.64), 3rd (r=0.45) and even 4th order neighbours (r=0.42). It appears
      that tall stature communities generate tall people, short stature communities
      generate short people, and migrants orientate towards the new height target of
      their host population (community effect on growth). 

PMID- 24940855
TI  - Clinical analysis of 102 cases of Epstein-Barr virus infections in Chinese
      children.
AB  - The purpose of this study is to investigate the clinical manifestations and
      disease severity, to evaluate the recent trend of clinical manifestations and
      differences in the clinical and laboratory findings of EBV-associated IM
      (infectious mononucleosis) according to the age of children. We retrospectively
      collected cases on hospitalized patients a majority of 7 years old with
      characteristic symptoms of IM and serologically diagnosed EBV-associated IM at
      Shaanxi Provincial Peoples University Hospital in Xi'an from Apr, 2012 to Oct,
      2013. All their medical records were reviewed and analyzed. For each patient,
      clinical, laboratory data and outcome were collected retrospectively and compared
      to previous studies to evaluate the differences between the clinical and
      laboratory findings of patients of different ages. The clinical manifestations in
      children with EB virus infection varied. There were 60 (58.8%) cases of children
      with infectious mononucleosis, 26 (25.49%) cases of Epstein-barr virus
      infection,16 cases of the atypical EB virus infection, accounting for 15.67%. 78%
      children were under 7 years of age, 12% were 7 to 14 years of age. There are
      differences in the symptoms and signs among the different age groups. The
      clinical manifestations in children with EB virus infection involved multiple
      systems and produced harm is heavier and should be paid attention to during the
      treatment. The disease continues to occur mostly in children under 10 years of
      age. When compared to previous Chinese studies about 15 years ago, the age
      distribution was similar and the incidence of hepatosplenomegaly was lower in our
      study. 

PMID- 24940856
TI  - Fuzzy approaches in pediatrics.
AB  - In this paper we present a review of applications of fuzzy methods in children
      and adolescence health care. Based on the several examples, available from
      journal papers, conference proceedings and book chapters we have concentrate
      ourselves on problems in the pediatrics that have been or can be solved with the
      help of fuzzy methodology. The paper is organised as follows. In section I we
      consider the general considerations about fuzzy logic and medicine. Section II
      considers the basics of fuzzy sets and fuzzy logic, the main methodological
      approaches for medical practical applications. Section III describes problems and
      the way of their solving using fuzzy approaches in pediatrics. Conclusions
      summarise the review in Section IV. 

PMID- 24940857
TI  - Congenital diseases of the gastrointestinal tract.
AB  - With the rapid increase in knowledge on the genetic origin of diseases within the
      gastrointestinal tract the number of congenital diseases, which already manifest
      during childhood have drastically increased. Due to the large application of
      molecular genetics the number is steadily increasing. To make the access to these
      rare diseases fast and efficient the data base of the National Library of
      Medicine (Online Mendelian Inheritance of Man - OMIN) is a very helpful online
      tool, with which all these disease entities can be found easily
      (http://www.ncbi.nlm.nih.gov/omim). Detailed tables are given to find most of the
      congenitally inherited disease, which affect the gastrointestinal tract. A
      variety of congenital diarrheas with disturbances of digestion, hydrolysis,
      absorption and secretion is described in detail: lactose intolerance, sucrose
      intolerance, glucose-galactose malabsorption, fructose malabsorption, trehalase
      and enterokinase deficiency, congenital chloride and sodium diarrhea, congenital
      hypomagnesaemia, primary bile acid malabsorption, acrodermatitis enteropathica
      and Menke's syndrome. Also described in detail are diseases with structural
      anomalies of the intestine like microvillous inclusion disease, congenital
      tufting enteropathy and IPEX syndrome. The diagnosis in the disturbances of
      carbohydrate hydrolysis or absorption can be established by H2-breath tests after
      appropriate sugar challenge. Treatment consists of elimination of the responsible
      sugar from the diet. The diagnosis of the congenital secretory diarrheas is
      established by investigation of electrolytes in blood and stool. Substitution of
      high doses of the responsible mineral can improve the clinical outcome. In
      acrodermatitis enteropathica low serum zinc level together with the typical skin
      lesions guide to the diagnosis. High doses of oral zinc aspartate can cure the
      symptoms of the disease. The diagnosis of structural congenital lesions of the
      intestine can be established by histology and/or electron microscopy and
      molecular identification of the responsible mutations. The treatment of these
      diseases is difficult and therefore the prognosis remains poor. Immunosupressive
      therapy, total parenteral nutrition and even intestinal or bone marrow
      transplantation are the only choice for treatment. 

PMID- 24940858
TI  - The health of adolescents around a world in transition.
AB  - Since several years, the health of adolescents is on the agenda of ministers,
      decision makers and health professionals. Around the world, while there has been
      a steady decrease of the death rates among young children, this is not the case
      for young people. This is mainly linked with the fact that mortality and
      morbidity during this period of life is largely linked with non communicable
      diseases and conditions, including deaths from injuries, suicide, homicides and
      drug abuse. Unplanned pregnancies, illegal abortions, newly acquired HIV
      infections are also situations that have short and long term consequences. This
      paper reviews the epidemiological data pertaining to adolescent health and
      disease. It proposes evidence-informed avenues as how to address these issues in
      the field of health care (e.g. adolescent friendly services) and of prevention
      and health promotion. It also stresses the importance of creating safe
      environments for the development and well-being of young people and thus, of an
      interdisciplinary and inter sectorial approach to their complex health problems
      and challenges. 

PMID- 24940859
TI  - [Medical-social peculiarities of health state of schoolchildren in Ukraine].
AB  - In the article there are results of the surveys on school children's health in
      Lviv region in years 2002 and 2012. The basic risk factors for functional
      disorders, school disadaptation syndrome, neurotic reactions are presented as
      well as the age prevalence of basic complaints. Among the factors that contribute
      to the decline of child's health level an important role belongs to the
      educational loading. It causes fast development of disadaptation syndrome with
      the neurotic reactions in different degree of expressiveness. The complex
      estimation of the children's health state and introduction of new technologies of
      revitalizing give an opportunity to prevent the increase of functional disorders
      and organic pathology in schoolchildren. 

PMID- 24940861
TI  - A need for phenotyping pediatric asthma in epidemiologic studies.
AB  - Epidemiological studies on pediatric asthma reveal a substantial variation in the
      prevalence of the disease. Differing population-specific data on the occurrence
      of the disease, defined as a physician-diagnosed asthma, are attributed to
      differences in risk factors, nosologic preferences, availability of diagnostic
      facilities, socio-economic factors, etc. As a result some findings could be
      affected by so-called underdiagnosis although in some populations overdiagnosis
      of pediatric asthma cannot be excluded. Diagnosing pediatric asthma can be
      difficult even in clinical setting. Among factors hampering that process
      heterogeneity of the disease plays an important role. Evidence show that asthma
      is not a single disease but it is a complex syndrome composed of similarly
      manifested disorders. As a result a significant scientific effort is directed to
      describe phenotypes of pediatric asthma. Two well known approaches to phenotyping
      include clinical and etiological assessment. The former approach takes into
      account the clinical presentation. The latter one involves recognition of the
      circumstances that precede the symptom manifestation in the disease: 'virus
      induced asthma', 'exercise-induced asthma', 'allergen-induced asthma',
      'unresolved asthma'. The mentioned approaches do not provide means of complete
      classification of the disease. A relatively novel and promising research area in
      the field of phenotyping asthma takes advantage of biomonitoring. Biomarkers of
      allergy and immunological responses are used in clinical setting (for example:
      assessment of atopy, eosinophils count, FENO), however many tests need more
      validation. Of particular interest is availability of non-invasive biomarkers,
      their repeatability, sensitivity and specificity. Several national and
      international guidelines and recommendations point to the importance of specific
      studies addressing the role of biomonitoring in phenotyping asthma.
      Epidemiological perspective investigations into biomarkers in pediatric asthma
      can contribute to observational and analytical goals. Focus on specific
      phenotypes and its components could provide a better opportunity to explore
      asthmatic disorders in children. Epidemiological projects should also address
      validation issues. Both research directions deserve more attention in
      epidemiological studies on pediatric asthma. 

PMID- 24940860
TI  - Childhood vasculitis hospitalizations in Spain, 1997-2011.
AB  - The aim of this study is to describe the childhood vasculitis hospital burden in
      Spain (1997-2011), considering type of disease, hospitalization rates and time
      trends. Data were obtained from the National Discharges Basic Minimum Data Set
      (National Patient Data Base). Inpatient events of children younger than 15 years
      of age were analyzed. Principal diagnosis of vasculitis were selected according
      Ninth Revision of the International Classification of Diseases: Takayasu
      arteritis, Polyarteritis nodosa, Kawasaki disease, Wegener's granulomatosis,
      Churg-Strauss syndrome, and Henoch-Schonlein purpura. A total of 14518 children
      hospitalizations related to vasculitis were identified in Spain from 1997 to
      2011. The average hospitalization rate for children was 13.33+/-1.71 per 100,000.
      Henoch-Schonlein purpura and Kawasaki disease were the most common type of
      vasculitis, hospitalization rates were 11.00 and 3.97 per 100,000 children,
      respectively. Other vasculitis hospitalizations are much rare in childhood.
      Average length of stay was 6.04 days and estimated cost per inpatient hospital
      care was 2,847?. Hospital case fatality rate was 0.05% for overall vasculitis. In
      conclusion, epidemiological data of childhood vasculitis are useful both to
      health decision-making and to identify research priorities. 

PMID- 24940863
TI  - Some personal views on pediatrics and not only...
AB  - In the paper there are presented author's personal views on youth education,
      medical education, child and adolescent physiology, some other common medical and
      pediatric issues. The role of the physician as an educator of the child is
      underlined. The pediatrician must be the main advisor to the society, school and
      family in the matter of youth education, contribute to their optimal self
      realization. The importance of moral values, gender peculiarities and cultural
      codes are emphasized. The imprinting of cultural codes should be considered as a
      biological basis of patriotism. The effectiveness of the implementation of
      healthy life style is discussed. The opinion regarding the protection of youth
      from potentially negative effects on their development and behavior is expressed.
      It would be purposeful to give more consideration to the fundamental research,
      particularly to the problem of age-related morphological and functional
      peculiarities of the growing organism in the conditions of norm and pathology.
      One should have in mind the importance of research of the combination of harmful
      factors for the organism. The elaboration of empathic and optimistic attitudes
      should be considered as the very important goals of medical education. The
      differential usage of clinical guidelines is discussed. It is mentioned the
      purposefulness of more wide application of fuzzy logic approaches in medicine.
      The items of rare diseases, individualized medicine, alternative medicine and
      bacteriophage therapy are discussed as well. 

PMID- 24940862
TI  - Familial Mediterranean fever in Georgia.
AB  - Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder
      caused by mutations in the MEFV gene. Carrier rates are known to be particularly
      high among Sephardic Jews, Turks, Armenians and Arab populations. Our literature
      survey regarding FMF and MEFV mutations in Georgia revealed a lack of existing
      studies. We applied multiplex PCR and reverse-hybridization teststrips (FMF
      StripAssay) to simultaneously analyze twelve common MEFV mutations in DNA samples
      from dried blood on filter cards, which had been obtained from 202 unselected
      newborns at various hospitals in Tbilisi, Georgia. We found 30 samples to be
      heterozygous and one to be compound heterozygous or carrier of a complex allele
      (two mutations in cis). The carrier rate of MEFV mutations (15.3%) was
      remarkable. The most frequently observed variants were E148Q (15x), M680I G/C
      (5x) and M694V (4x). Five other MEFV mutations were found at lower prevalence
      (V726A, A744S, R761H: 2x each; P369S, F479L: 1x each). Based on these new
      findings, the awareness for FMF and the availability of appropriate testing
      should be further promoted in Georgia. 

PMID- 24940864
TI  - A distributed air index based on maximum boundary rectangle over grid-cells for
      wireless non-flat spatial data broadcast.
AB  - In the pervasive computing environment using smart devices equipped with various
      sensors, a wireless data broadcasting system for spatial data items is a natural
      way to efficiently provide a location dependent information service, regardless
      of the number of clients. A non-flat wireless broadcast system can support the
      clients in accessing quickly their preferred data items by disseminating the
      preferred data items more frequently than regular data on the wireless channel.
      To efficiently support the processing of spatial window queries in a non-flat
      wireless data broadcasting system, we propose a distributed air index based on a
      maximum boundary rectangle (MaxBR) over grid-cells (abbreviated DAIM), which uses
      MaxBRs for filtering out hot data items on the wireless channel. Unlike the
      existing index that repeats regular data items in close proximity to hot items at
      same frequency as hot data items in a broadcast cycle, DAIM makes it possible to
      repeat only hot data items in a cycle and reduces the length of the broadcast
      cycle. Consequently, DAIM helps the clients access the desired items quickly,
      improves the access time, and reduces energy consumption. In addition, a MaxBR
      helps the clients decide whether they have to access regular data items or not.
      Simulation studies show the proposed DAIM outperforms existing schemes with
      respect to the access time and energy consumption. 

PMID- 24940865
TI  - A magnetic sensor with amorphous wire.
AB  - Using a FeCoSiB amorphous wire and a coil wrapped around it, we have developed a
      sensitive magnetic sensor. When a 5 mm long amorphous wire with the diameter of
      0.1 mm was used, the magnetic field noise spectrum of the sensor was about 30
      pT/OHz above 30 Hz. To show the sensitivity and the spatial resolution, the
      magnetic field of a thousand Japanese yen was scanned with the magnetic sensor. 

PMID- 24940867
TI  - Sparse fusion imaging for a moving target in T/R-R configuration.
AB  - For high resolution imaging of a non-cooperative moving target, this paper
      proposes a sparse fusion imaging method. The imaging system contains two radar
      stations, which are separated by a certain bistatic angle and configured in a
      transmitter/receiver-receiver (T/R-R) manner. Consequently, two synthetic
      apertures are obtained at the same time from different aspect angles. By
      coherently fusing the echoes of the two radars, a virtual aperture spanned by
      these two sub-apertures can be constructed, which is larger than either of the
      sub-apertures; thus, the cross-range resolution of the image is enhanced.
      Moreover, the fusion of the echoes is realized by exploiting the sparse
      scattering property of the target. Then, based on the maximum a posteriori (MAP)
      criterion, the T/R-R fusion imaging problem is converted into a sparse signal
      recovery problem with unknown parameters. Finally, it is solved in an iterative
      manner, which contains two steps, i.e., sparse imaging and parameter estimation.
      Simulation results show that the proposed sparse fusion imaging method can
      improve the cross-range resolution significantly compared to inverse synthetic
      aperture radar (ISAR) within the same coherent processing interval (CPI). 

PMID- 24940866
TI  - Voltammetric detection of S100B protein using His-tagged receptor domains for
      advanced glycation end products (RAGE) immobilized onto a gold electrode surface.
AB  - In this work we report on an electrochemical biosensor for the determination of
      the S100B protein. The His-tagged VC1 domains of Receptors for Advanced Glycation
      End (RAGE) products used as analytically active molecules were covalently
      immobilized on a monolayer of a thiol derivative of pentetic acid (DPTA) complex
      with Cu(II) deposited on a gold electrode surface. The recognition processes
      between the RAGE VC1 domain and the S100B protein results in changes in the redox
      activity of the DPTA-Cu(II) centres which were measured by Osteryoung square-wave
      voltammetry (OSWV). In order to verify whether the observed analytical signal
      originates from the recognition process between the His6-RAGE VC1 domains and the
      S100B protein, the electrode modified with the His6-RAGE C2 and His6-RAGE VC1
      deleted domains which have no ability to bind S100B peptides were applied. The
      proposed biosensor was quite sensitive, with a detection limit of 0.52 pM
      recorded in the buffer solution. The presence of diluted human plasma and 10 nM
      Abeta(1-40) have no influence on the biosensor performance.

PMID- 24940868
TI  - WO3/W nanopores sensor for chemical oxygen demand (COD) determination under
      visible light.
AB  - A sensor of a WO3 nanopores electrode combined with a thin layer reactor was
      proposed to develop a Chemical Oxygen Demand (COD) determination method and solve
      the problem that the COD values are inaccurately determined by the standard
      method. The visible spectrum, e.g., 420 nm, could be used as light source in the
      sensor we developed, which represents a breakthrough by limiting of UV light
      source in the photoelectrocatalysis process. The operation conditions were
      optimized in this work, and the results showed that taking NaNO3 solution at the
      concentration of 2.5 mol.L(-1) as electrolyte under the light intensity of 214
      MUW.cm(-2) and applied bias of 2.5 V, the proposed method is accurate and well
      reproducible, even in a wide range of pH values. Furthermore, the COD values
      obtained by the WO3 sensor were fitted well with the theoretical COD value in the
      range of 3-60 mg.L(-1) with a limit value of 1 mg.L(-1), which reveals that the
      proposed sensor may be a practical device for monitoring and controlling surface
      water quality as well as slightly polluted water.

PMID- 24940869
TI  - Transient secondary organic aerosol formation from limonene ozonolysis in indoor
      environments: impacts of air exchange rates and initial concentration ratios.
AB  - Secondary organic aerosol (SOA) results from the oxidation of reactive organic
      gases (ROGs) and is an indoor particle source. The aerosol mass fraction (AMF),
      a.k.a. SOA yield, quantifies the SOA forming potential of ROGs and is the ratio
      of generated SOA to oxidized ROG. The AMF depends on the organic aerosol
      concentration, as well as the prevalence of later generation reactions. AMFs have
      been measured in unventilated chambers or steady-state flow through chambers.
      However, indoor settings have outdoor air exchange, and indoor SOA formation
      often occurs when ROGs are transiently emitted, for instance from emissions of
      cleaning products. Herein, we quantify "transient AMFs" from ozonolysis of pulse
      emitted limonene in a ventilated chamber, for 18 experiments at low (0.28 h(-1)),
      moderate (0.53 h(-1)), and high (0.96 h(-1)) air exchange rates (AER) with
      varying initial ozone-limonene ratios. Transient AMFs increased with the amount
      of ROG reacted; AMFs also increased with decreasing AERs and increasing initial
      ozone-limonene ratios, which together likely promoted more ozone reactions with
      the remaining exocyclic bond of oxidized limonene products in the SOA phase.
      Knowing the AER and initial ozone-limonene ratio is crucial to predict indoor
      transient SOA behavior accurately. 

PMID- 24940870
TI  - An elusive hydridoaluminum(I) complex for facile C-H and C-O bond activation of
      ethers and access to its isolable hydridogallium(I) analogue: syntheses,
      structures, and theoretical studies.
AB  - The reaction of AlBr3 with 1 molar equiv of the chelating bis(N-heterocyclic
      carbene) ligand bis(N-Dipp-imidazole-2-ylidene)methylene (bisNHC, 1) affords
      [(bisNHC)AlBr2](+)Br(-) (2) as an ion pair in high yield, representing the first
      example of a bisNHC-Al(III) complex. Debromination of the latter with 1 molar
      equiv of K2Fe(CO)4 in tetrahydrofuran (THF) furnishes smoothly, in a redox
      reaction, the (bisNHC)(Br)Al[Fe(CO)4] complex 3, in which the Al(I) center is
      stabilized by the Fe(CO)4 moiety through Al(I):->Fe(0) coordination. Strikingly,
      the Br/H ligand exchange reactions of 3 using potassium hydride as a hydride
      source in THF or tetrahydropyran (THP) do not yield the anticipated
      hydridoaluminum(I) complex (bisNHC)Al(H)[Fe(CO)4] (4a) but instead lead to
      (bisNHC)Al(2-cyclo-OC4H7)[Fe(CO)4] (4) and (bisNHC)Al(2-cyclo-OC5H9)[Fe(CO)4]
      (5), respectively. The latter are generated via C-H bond activation at the alpha
      carbon positions of THF and THP, respectively, in good yields with concomitant
      elimination of dihydrogen. This is the first example whereby a low-valent main
      group hydrido complex facilitates metalation of sp(3) C-H bonds. Interestingly,
      when K[BHR3] (R = Et, sBu) is employed as a hydride source to react with 3 in
      THF, the reaction affords (bisNHC)Al(OnBu)[Fe(CO)4] (6) as the sole product
      through C-O bond activation and ring opening of THF. The mechanisms for these
      novel C-H and C-O bond activations mediated by the elusive hydridoaluminum(I)
      complex 4a were elucidated by density functional theory (DFT) calculations. In
      contrast, the analogous hydridogallium(I) complex (bisNHC)Ga(H)[Fe(CO)4] (9) can
      be obtained directly in high yield by the reaction of the (bisNHC)Ga(Cl)[Fe(CO)4]
      precursor 8 with 1 molar equiv of K[BHR3] (R = Et, sBu) in THF at room
      temperature. The isolation of 9 and its inertness toward cyclic ethers might be
      attributed to the higher electronegativity of gallium versus aluminum. The
      stronger Ga(I)-H bond, in turn, hampers alpha-C-H metalation or C-O bond cleavage
      in cyclic ethers, the latter of which is supported by DFT calculations. 

PMID- 24940871
TI  - P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or
      to N-acetylcysteine supplementation [corrected].
AB  - Previous studies in our laboratory showed that N-acetylcysteine supplementation
      or aerobic training reduced oxidative stress and the progression of diabetic
      nephropathy in rats. The P2X(7 receptor is up-regulated in pathological
      conditions, such as diabetes mellitus. This up-regulation is related to oxidative
      stress and induces tissue apoptosis or necrosis. The aim of the present study is
      to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted
      to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in
      male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on
      a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By
      confocal microscopy, as compared to control, the kidneys of diabetic rats showed
      increased P2 * 7 receptor expression and a higher activation in response to
      2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and
      adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations
      were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We
      also observed measured proteinuria and albuminuria (early marker of diabetic
      nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7)
      receptor expression, which was also correlated to NO*, thus associating this
      receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor
      inhibition associated with the maintenance of redox homeostasis could be useful
      as coadjuvant treatment to delay the progression of diabetic nephropathy.

PMID- 24940872
TI  - Staphylococcus aureus in vitro secretion of alpha toxin (hla) correlates with the
      affiliation to clonal complexes.
AB  - The alpha toxin of Staphylococcus aureus is a pore forming toxin that penetrates
      host cell membranes causing osmotic swelling, rupture, lysis and subsequently
      cell death. Haemolysin alpha is toxic to a wide range of different mammalian
      cells; i.e., neurotoxic, dermonecrotic, haemolytic, and it can cause lethality in
      a wide variety of animals. In this study, the in vitro alpha toxin production of
      648 previously genotyped isolates of S. aureus was measured quantitatively using
      antibody microarrays. Isolates originated from medical and veterinary settings
      and were selected in order to represent diverse clonal complexes and defined
      clinical conditions. Generally, the production of alpha toxin in vitro is related
      to the clonal complex affiliation. For clonal complexes CC22, CC30, CC45, CC479,
      CC705 and others, invariably no alpha toxin production was noted under the given
      in vitro conditions, while others, such as CC1, CC5, CC8, CC15 or CC96 secreted
      variable or high levels of alpha toxin. There was no correlation between alpha
      toxin yield and clinical course of the disease, or between alpha toxin yield and
      host species. 

PMID- 24940875
TI  - Arabidopsis CAP1-mediated ammonium sensing required reactive oxygen species in
      plant cell growth.
AB  - [Ca 2+]cyt-associated protein kinase (CAP) gene 1 is a receptor-like kinase that
      belongs to CrRLK1L (Catharanthus roseus Receptor like kinase) subfamily. CAP1 has
      been identified as a novel modulator of NH 4+ in the tonoplast, which regulates
      root hair growth by maintaining the cytoplasmic Ca 2+ gradients. Different
      expression pattern of tonoplast intrinsic protein (TIP2;3) in the CAP1 knock out
      mutant and wild type on Murashige and Skoog (MS) medium suggested that CAP1
      influences transport activity to regulate the compartmentalization of NH 4+ into
      vacuole. Lower expression level of Oxidative Signal-Inducible1(OXI1) in the cap1
      1 root and the abnormal reactive oxygen species (ROS) gradient in root hair of
      cap1-1 on MS medium indicated that ROS signaling involve in CAP1-regulated root
      hair growth. Wild-type-like ROS distribution pattern in the cap1-1 root hair can
      be reestablished in seedlings grown on NH 4+ deficient medium, which indicated
      that CAP1 functions as a sensor for NH 4+ signaling in maintaining tip-focused
      ROS gradient in root hairs polar growth.

PMID- 24940873
TI  - Targeting the Wnt/beta-catenin signaling pathway in liver cancer stem cells and
      hepatocellular carcinoma cell lines with FH535.
AB  - Activation of the Wnt/beta-catenin pathway has been observed in at least 1/3 of
      hepatocellular carcinomas (HCC), and a significant number of these have mutations
      in the beta-catenin gene. Therefore, effective inhibition of this pathway could
      provide a novel method to treat HCC. The purposed of this study was to determine
      whether FH535, which was previously shown to block the beta-catenin pathway,
      could inhibit beta-catenin activation of target genes and inhibit proliferation
      of Liver Cancer Stem Cells (LCSC) and HCC cell lines. Using beta-catenin
      responsive reporter genes, our data indicates that FH535 can inhibit target gene
      activation by endogenous and exogenously expressed beta-catenin, including the
      constitutively active form of beta-catenin that contains a Serine37Alanine
      mutation. Our data also indicate that proliferation of LCSC and HCC lines is
      inhibited by FH535 in a dose-dependent manner, and that this correlates with a
      decrease in the percentage of cells in S phase. Finally, we also show that
      expression of two well-characterized targets of beta-catenin, Cyclin D1 and
      Survivin, is reduced by FH535. Taken together, this data indicates that FH535 has
      potential therapeutic value in treatment of liver cancer. Importantly, these
      results suggest that this therapy may be effective at several levels by targeting
      both HCC and LCSC. 

PMID- 24940876
TI  - 3D face recognition based on multiple keypoint descriptors and sparse
      representation.
AB  - Recent years have witnessed a growing interest in developing methods for 3D face
      recognition. However, 3D scans often suffer from the problems of missing parts,
      large facial expressions, and occlusions. To be useful in real-world
      applications, a 3D face recognition approach should be able to handle these
      challenges. In this paper, we propose a novel general approach to deal with the
      3D face recognition problem by making use of multiple keypoint descriptors (MKD)
      and the sparse representation-based classification (SRC). We call the proposed
      method 3DMKDSRC for short. Specifically, with 3DMKDSRC, each 3D face scan is
      represented as a set of descriptor vectors extracted from keypoints by meshSIFT.
      Descriptor vectors of gallery samples form the gallery dictionary. Given a probe
      3D face scan, its descriptors are extracted at first and then its identity can be
      determined by using a multitask SRC. The proposed 3DMKDSRC approach does not
      require the pre-alignment between two face scans and is quite robust to the
      problems of missing data, occlusions and expressions. Its superiority over the
      other leading 3D face recognition schemes has been corroborated by extensive
      experiments conducted on three benchmark databases, Bosphorus, GavabDB, and
      FRGC2.0. The Matlab source code for 3DMKDSRC and the related evaluation results
      are publicly available at
      http://sse.tongji.edu.cn/linzhang/3dmkdsrcface/3dmkdsrc.htm. 

PMID- 24940874
TI  - Neural extrapolation of motion for a ball rolling down an inclined plane.
AB  - It is known that humans tend to misjudge the kinematics of a target rolling down
      an inclined plane. Because visuomotor responses are often more accurate and less
      prone to perceptual illusions than cognitive judgments, we asked the question of
      how rolling motion is extrapolated for manual interception or drawing tasks. In
      three experiments a ball rolled down an incline with kinematics that differed as
      a function of the starting position (4 different positions) and slope (30 degrees
      , 45 degrees  or 60 degrees ). In Experiment 1, participants had to punch the
      ball as it fell off the incline. In Experiment 2, the ball rolled down the
      incline but was stopped at the end; participants were asked to imagine that the
      ball kept moving and to punch it. In Experiment 3, the ball rolled down the
      incline and was stopped at the end; participants were asked to draw with the hand
      in air the trajectory that would be described by the ball if it kept moving. We
      found that performance was most accurate when motion of the ball was visible
      until interception and haptic feedback of hand-ball contact was available
      (Experiment 1). However, even when participants punched an imaginary moving ball
      (Experiment 2) or drew in air the imaginary trajectory (Experiment 3), they were
      able to extrapolate to some extent global aspects of the target motion, including
      its path, speed and arrival time. We argue that the path and kinematics of a ball
      rolling down an incline can be extrapolated surprisingly well by the brain using
      both visual information and internal models of target motion. 

PMID- 24940877
TI  - Differential acetylation of histone H3 at the regulatory region of OsDREB1b
      promoter facilitates chromatin remodelling and transcription activation during
      cold stress.
AB  - The rice ortholog of DREB1, OsDREB1b, is transcriptionally induced by cold stress
      and over-expression of OsDREB1b results in increase tolerance towards high salt
      and freezing stress. This spatio-temporal expression of OsDREB1b is preceded by
      the change in chromatin structure at the promoter and the upstream region for
      gene activation. The promoter and the upstream region of OsDREB1b genes appear to
      be arranged into a nucleosome array. Nucleosome mapping of ~ 700 bp upstream
      region of OsDREB1b shows two positioned nucleosomes between -610 to -258 and a
      weakly positioned nucleosome at the core promoter and the TSS. Upon cold stress,
      there is a significant change in the nucleosome arrangement at the upstream
      region with increase in DNaseI hypersensitivity or MNase digestion in the
      vicinity of cis elements and TATA box at the core promoter. ChIP assays shows
      hyper-acetylation of histone H3K9 throughout the locus whereas region specific
      increase was observed in H3K14ac and H3K27ac. Moreover, there is an enrichment of
      RNA PolII occupancy at the promoter region during transcription activation. There
      is no significant change in the H3 occupancy in OsDREB1b locus negating the
      possibility of nucleosome loss during cold stress. Interestingly, cold induced
      enhanced transcript level of OsDREB1b as well as histone H3 acetylation at the
      upstream region was found to diminish when stressed plants were returned to
      normal temperature. The result indicates absolute necessity of changes in
      chromatin conformation for the transcription up-regulation of OsDREB1b gene in
      response to cold stress. The combined results show the existence of closed
      chromatin conformation at the upstream and promoter region of OsDREB1b in the
      transcription "off" state. During cold stress, changes in region specific histone
      modification marks promote the alteration of chromatin structure to facilitate
      the binding of transcription machinery for proper gene expression.

PMID- 24940878
TI  - Comparison of the transcriptomes of ginger (Zingiber officinale Rosc.) and mango
      ginger (Curcuma amada Roxb.) in response to the bacterial wilt infection.
AB  - Bacterial wilt in ginger (Zingiber officinale Rosc.) caused by Ralstonia
      solanacearum is one of the most important production constraints in tropical, sub
      tropical and warm temperature regions of the world. Lack of resistant genotype
      adds constraints to the crop management. However, mango ginger (Curcuma amada
      Roxb.), which is resistant to R. solanacearum, is a potential donor, if the exact
      mechanism of resistance is understood. To identify genes involved in resistance
      to R. solanacearum, we have sequenced the transcriptome from wilt-sensitive
      ginger and wilt-resistant mango ginger using Illumina sequencing technology. A
      total of 26387032 and 22268804 paired-end reads were obtained after quality
      filtering for C. amada and Z. officinale, respectively. A total of 36359 and
      32312 assembled transcript sequences were obtained from both the species. The
      functions of the unigenes cover a diverse set of molecular functions and
      biological processes, among which we identified a large number of genes
      associated with resistance to stresses and response to biotic stimuli. Large
      scale expression profiling showed that many of the disease resistance related
      genes were expressed more in C. amada. Comparative analysis also identified genes
      belonging to different pathways of plant defense against biotic stresses that are
      differentially expressed in either ginger or mango ginger. The identification of
      many defense related genes differentially expressed provides many insights to the
      resistance mechanism to R. solanacearum and for studying potential pathways
      involved in responses to pathogen. Also, several candidate genes that may
      underline the difference in resistance to R. solanacearum between ginger and
      mango ginger were identified. Finally, we have developed a web resource, ginger
      transcriptome database, which provides public access to the data. Our study is
      among the first to demonstrate the use of Illumina short read sequencing for de
      novo transcriptome assembly and comparison in non-model species of Zingiberaceae.

PMID- 24940879
TI  - Long-term dynamics of bluetongue virus in wild ruminants: relationship with
      outbreaks in livestock in Spain, 2006-2011.
AB  - Wild and domestic ruminants are susceptible to Bluetongue virus (BTV) infection.
      Three BTV serotypes (BTV-4, BTV-1 and BTV-8) have been detected in Spain in the
      last decade. Even though control strategies have been applied to livestock, BTV
      circulation has been frequently detected in wild ruminant populations in Spain.
      The aim of the present study is to assess the role for wild ruminants in
      maintaining BTV after the vaccination programs in livestock in mainland Spain. A
      total of 931 out 1,914 (48.6%) serum samples, collected from eight different wild
      ruminant species between 2006 and 2011, were BTV positive by ELISA. In order to
      detect specific antibodies against BTV-1, BTV-4 and BTV-8, positive sera were
      also tested by serumneutralisation test (SNT). From the ELISA positive samples
      that could be tested by SNT (687 out of 931), 292 (42.5%) showed neutralising
      antibodies against one or two BTV serotypes. For each BTV serotype, the number of
      outbreaks in livestock (11,857 outbreaks in total) was modelled with pure
      autoregressive models and the resulting smoothed values, representing the
      predicted number of BTV outbreaks in livestock at municipality level, were
      positively correlated with BTV persistence in wild species. The strength of this
      relationship significantly decreased as red deer (Cervus elaphus) population
      abundance increased. In addition, BTV RNA was detected by real time RT-PCR in 32
      out of 311 (10.3%) spleen samples from seropositive animals. Although BT
      outbreaks in livestock have decreased substantially after vaccination campaigns,
      our results indicated that wild ruminants have been exposed to BTV in territories
      where outbreaks in domestic animals occurred. The detection of BTV RNA and
      spatial association between BT outbreaks in livestock and BTV rates in red deer
      are consistent with the hypothesis of virus circulation and BTV maintenance
      within Iberian wild ruminant populations.

PMID- 24940880
TI  - Reliability and validity of the new Tanaka B Intelligence Scale scores: a group
      intelligence test.
AB  - OBJECTIVE: The present study evaluated the reliability and concurrent validity of
      the new Tanaka B Intelligence Scale, which is an intelligence test that can be
      administered on groups within a short period of time. METHODS: The new Tanaka B
      Intelligence Scale and Wechsler Intelligence Scale for Children-Third Edition
      were administered to 81 subjects (mean age +/- SD 15.2 +/- 0.7 years) residing in
      a juvenile detention home; reliability was assessed using Cronbach's alpha
      coefficient, and concurrent validity was assessed using the one-way analysis of
      variance intraclass correlation coefficient. Moreover, receiver operating
      characteristic analysis for screening for individuals who have a deficit in
      intellectual function (an FIQ<70) was performed. In addition, stratum-specific
      likelihood ratios for detection of intellectual disability were calculated.
      RESULTS: The Cronbach's alpha for the new Tanaka B Intelligence Scale IQ (BIQ)
      was 0.86, and the intraclass correlation coefficient with FIQ was 0.83. Receiver
      operating characteristic analysis demonstrated an area under the curve of 0.89
      (95% CI: 0.85-0.96). In addition, the stratum-specific likelihood ratio for the
      BIQ<=65 stratum was 13.8 (95% CI: 3.9-48.9), and the stratum-specific likelihood
      ratio for the BIQ>=76 stratum was 0.1 (95% CI: 0.03-0.4). Thus, intellectual
      disability could be ruled out or determined. CONCLUSION: The present results
      demonstrated that the new Tanaka B Intelligence Scale score had high reliability
      and concurrent validity with the Wechsler Intelligence Scale for Children-Third
      Edition score. Moreover, the post-test probability for the BIQ could be
      calculated when screening for individuals who have a deficit in intellectual
      function. The new Tanaka B Intelligence Test is convenient and can be
      administered within a variety of settings. This enables evaluation of
      intellectual development even in settings where performing intelligence tests
      have previously been difficult.

PMID- 24940881
TI  - Metabolic pattern of the acute phase of subarachnoid hemorrhage in a novel
      porcine model: studies with cerebral microdialysis with high temporal resolution.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) may produce cerebral
      ischemia and systemic responses including stress. To study immediate cerebral and
      systemic changes in response to aneurysm rupture, animal models are needed.
      OBJECTIVE: To study early cerebral energy changes in an animal model. METHODS:
      Experimental SAH was induced in 11 pigs by autologous blood injection to the
      anterior skull base, with simultaneous control of intracranial and cerebral
      perfusion pressures. Intracerebral microdialysis was used to monitor
      concentrations of glucose, pyruvate and lactate. RESULTS: In nine of the pigs, a
      pattern of transient ischemia was produced, with a dramatic reduction of cerebral
      perfusion pressure soon after blood injection, associated with a quick glucose
      and pyruvate decrease. This was followed by a lactate increase and a delayed
      pyruvate increase, producing a marked but short elevation of the lactate/pyruvate
      ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned
      toward baseline. The two remaining pigs had a more severe metabolic reaction with
      glucose and pyruvate rapidly decreasing to undetectable levels while lactate
      increased and remained elevated, suggesting persisting ischemia. CONCLUSION: The
      animal model simulates the conditions of SAH not only by deposition of blood in
      the basal cisterns, but also creating the transient global ischemic impact of
      aneurysmal SAH. The metabolic cerebral changes suggest immediate transient
      substrate failure followed by hypermetabolism of glucose upon reperfusion. The
      model has features that resemble spontaneous bleeding, and is suitable for future
      research of the early cerebral and systemic responses to SAH that are difficult
      to study in humans.

PMID- 24940882
TI  - Venom variation during prey capture by the cone snail, Conus textile.
AB  - Observations of the mollusc-hunting cone snail Conus textile during feeding
      reveal that prey are often stung multiple times in succession. While studies on
      the venom peptides injected by fish-hunting cone snails have become common, these
      approaches have not been widely applied to the analysis of the injected venoms
      from mollusc-hunters. We have successfully obtained multiple injected venom
      samples from C. textile individuals, allowing us to investigate venom
      compositional variation during prey capture. Our studies indicate that C. textile
      individuals alter the composition of prey-injected venom peptides during single
      feeding events. The qualitative results obtained by MALDI-ToF mass spectrometry
      are mirrored by quantitative changes in venom composition observed by reverse
      phase high performance liquid chromatography. While it is unclear why mollusc
      hunting cone snails inject prey multiple times prior to engulfment, our study
      establishes for the first time a link between this behavior and compositional
      changes of the venom during prey capture. Changes in venom composition during
      hunting may represent a multi-step strategy utilized by these venomous animals to
      slow and incapacitate prey prior to engulfment. 

PMID- 24940885
TI  - Fish predation by semi-aquatic spiders: a global pattern.
AB  - More than 80 incidences of fish predation by semi-aquatic spiders--observed at
      the fringes of shallow freshwater streams, rivers, lakes, ponds, swamps, and fens
      -are reviewed. We provide evidence that fish predation by semi-aquatic spiders is
      geographically widespread, occurring on all continents except Antarctica. Fish
      predation by spiders appears to be more common in warmer areas between 40 degrees
      S and 40 degrees  N. The fish captured by spiders, usually ranging from 2-6 cm
      in length, are among the most common fish taxa occurring in their respective
      geographic area (e.g., mosquitofish [Gambusia spp.] in the southeastern USA, fish
      of the order Characiformes in the Neotropics, killifish [Aphyosemion spp.] in
      Central and West Africa, as well as Australian native fish of the genera
      Galaxias, Melanotaenia, and Pseudomugil). Naturally occurring fish predation has
      been witnessed in more than a dozen spider species from the superfamily
      Lycosoidea (families Pisauridae, Trechaleidae, and Lycosidae), in two species of
      the superfamily Ctenoidea (family Ctenidae), and in one species of the
      superfamily Corinnoidea (family Liocranidae). The majority of reports on fish
      predation by spiders referred to pisaurid spiders of the genera Dolomedes and
      Nilus (>75% of observed incidences). There is laboratory evidence that spiders
      from several more families (e.g., the water spider Argyroneta aquatica
      [Cybaeidae], the intertidal spider Desis marina [Desidae], and the 'swimming'
      huntsman spider Heteropoda natans [Sparassidae]) predate fish as well. Our
      finding of such a large diversity of spider families being engaged in fish
      predation is novel. Semi-aquatic spiders captured fish whose body length exceeded
      the spiders' body length (the captured fish being, on average, 2.2 times as long
      as the spiders). Evidence suggests that fish prey might be an occasional prey
      item of substantial nutritional importance.

PMID- 24940883
TI  - DMXAA causes tumor site-specific vascular disruption in murine non-small cell
      lung cancer, and like the endogenous non-canonical cyclic dinucleotide STING
      agonist, 2'3'-cGAMP, induces M2 macrophage repolarization.
AB  - The vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a
      murine agonist of the stimulator of interferon genes (STING), appears to target
      the tumor vasculature primarily as a result of stimulating pro-inflammatory
      cytokine production from tumor-associated macrophages (TAMs). Since there were
      relatively few reports of DMXAA effects in genetically-engineered mutant mice
      (GEMM), and models of non-small cell lung cancer (NSCLC) in particular, we
      examined both the effectiveness and macrophage dependence of DMXAA in various
      NSCLC models. The DMXAA responses of primary adenocarcinomas in K-rasLA1/+
      transgenic mice, as well as syngeneic subcutaneous and metastatic tumors,
      generated by a p53R172HDeltag/+; K-rasLA1/+ NSCLC line (344SQ-ELuc), were
      assessed both by in vivo bioluminescence imaging as well as by histopathology.
      Macrophage-dependence of DMXAA effects was explored by clodronate liposome
      mediated TAM depletion. Furthermore, a comparison of the vascular structure
      between subcutaneous tumors and metastases was carried out using micro-computed
      tomography (micro-CT). Interestingly, in contrast to the characteristic
      hemorrhagic necrosis produced by DMXAA in 344SQ-ELuc subcutaneous tumors, this
      agent failed to cause hemorrhagic necrosis of either 344SQ-ELuc-derived
      metastases or autochthonous K-rasLA1/+ NSCLCs. In addition, we found that
      clodronate liposome-mediated depletion of TAMs in 344SQ-ELuc subcutaneous tumors
      led to non-hemorrhagic necrosis due to tumor feeding-vessel occlusion. Since
      NSCLC were comprised exclusively of TAMs with anti-inflammatory M2-like
      phenotype, the ability of DMXAA to re-educate M2-polarized macrophages was
      examined. Using various macrophage phenotypic markers, we found that the STING
      agonists, DMXAA and the non-canonical endogenous cyclic dinucleotide, 2'3'-cGAMP,
      were both capable of re-educating M2 cells towards an M1 phenotype. Our findings
      demonstrate that the choice of preclinical model and the anatomical site of a
      tumor can determine the vascular disrupting effectiveness of DMXAA, and they also
      support the idea of STING agonists having therapeutic utility as TAM repolarizing
      agents. 

PMID- 24940886
TI  - A variant of IL6R is associated with the recurrence of atrial fibrillation after
      catheter ablation in a Chinese Han population.
AB  - BACKGROUND: Recent studies have identified a variant, rs4845625, in the
      interleukin-6 receptor (IL6R) gene associated with Atrial Fibrillation (AF).
      Levels of circulating interleukin-6 and other proinflammatory molecules have
      consistently been associated with a risk for AF and its recurrence after catheter
      ablation. This study tested the hypothesis that variant rs4845625 is associated
      with AF recurrence after catheter ablation in a Chinese Han population. METHODS:
      A total of 278 consecutive patients (mean age 59.4+/-11.5 years, 43% female) with
      paroxysmal (36.0%), persistent (59.7%), and permanent (4.3%) AF who underwent
      catheterablation from 2007-2011, were included in this study. Patients were
      monitored for 12 months for a recurrence of AF. The SNP rs4845625 was genotyped
      using high resolution melting analysis. RESULTS: In our study cohort, an early
      recurrence of AF (ERAF), defined as a recurrence within the first 4 weeks, was
      observed in 42.8% of the patients, whereas late recurrence of AF (LRAF) (between
      3 and 12 months) occurred in 25.9% of the patients. No significant differences in
      baseline clinical or echocardiographic characteristics were observed between
      patients with ERAF and LRAF. In contrast, the presence of the T allele of
      rs4845625 was associated with an increase in the risk for both ERAF (odds ratio
      [OR]: 1.84, 95% confidence interval [CI]: 1.31-2.59, p = 4.10*10-4) and LRAF (OR:
      1.92, 95% CI: 1.30-2.81, p = 0.001). Furthermore, this association was
      significant after adjustments for age, sex, hypertension, diabetes and other risk
      factors. No significant relationship between rs4845625 and serum levels of IL6
      was observed. CONCLUSIONS: In this study, a variant of the IL6R gene, rs4845625,
      was found confer risk to AF recurrence after catheter ablation in a Chinese Han
      population. Our findings indicated that the IL6R pathway or inflammation may play
      important rols in the recurrence of AF after catheter ablation.

PMID- 24940887
TI  - [Detection of antibacterial resistance by MALDI-TOF mass spectrometry].
AB  - In the last decade we have witnessed a remarkable increase in the number of
      strains isolated in hospitals that are producing extended spectrum beta
      lactamases (ESBL) or, more recently, carbapenemases. This makes clear the need
      for a system for rapid detection of these resistance mechanisms that allow the
      selection of the most suitable antibiotic treatment in order to improve patient
      care. Recent data support the possibility of using mass spectrometry (MS),
      specifically MALDI -TOF (Matrix-Assisted Laser Desorption / Ionization, Time-of
      Flight ) systems to identify specific resistance mechanisms and their use offers
      several advantages. First, the economic cost of each determination is clearly
      inferior to the classical molecular techniques for detection of resistance genes.
      Second, detection of resistance by MALDI -TOF reduces the time for obtaining
      results compared to the routine methods currently employed. Finally, the
      possibility that this method allows us to detect enzymes not previously
      characterized, that there is no information about the genes that encode them.
      Therefore, we believe that this may be a good tool to implement in clinical
      microbiology laboratories. This review aims to present the latest developments in
      this field. 

PMID- 24940888
TI  - [Reasons for antiretroviral treatment change in HIV+ patients in Spain in 2010
      2011. SWITCH AUDIT Study].
AB  - Survey in 349 HIV infected subjects in 19 Spanish Hospitals in 2010-2011, to
      assess the reasons for antiretroviral treatment change. Simplification was the
      most frequent reason for change (37%), followed by toxicity (30%) and treatment
      failure (21%). There were statistically significant differences according to
      treatment line and transmission category. In conclusion, in many patients
      treatment is changed in order to obtain the benefits of a regimen easier to
      follow. 

PMID- 24940889
TI  - [Seroprevalence of measles, rubella, mumps and varicella in health workers in the
      Community of Madrid].
AB  - BACKGROUND: The vaccination of health workers has a large repercussion on the
      health of the workers, the patients and the population in general. Due to this,
      we proposed to discover the serological status for varicella, rubella, mumps and
      measles in the workers of a tertiary hospital in Madrid. METHODS: We have
      conducted a retrospective epidemiological study of 1060 health workers, obtaining
      information such as age, sex, service area, employment status, pre-exposure
      vaccination and post-vaccination serology and vaccination status. RESULTS: In the
      population studied, 90.1% were protected against varicella, 65.6% against mumps,
      95.6% against rubella and 92.9% against measles. There is no better protection
      against these illnesses for workers who treat patients directly, workers who
      treat immunosuppressed patients or for workers in services or units with a higher
      risk of infection. CONCLUSION: There is no better protection against varicella,
      rubella, mumps and measles for the workers who have higher risk of infection at
      work; and the workers who treat patients, that if they suffer these diseases,
      this could put their health at risk.

PMID- 24940890
TI  - [Sensitivity of three inmunocromathographic tests in faeces samples for
      Campylobacter and Salmonella detection in comparison to culture].
AB  - Introduction: Campylobacter sp. and Salmonella enterica are two of the main
      organisms causing gastroenteritis in our environment. Immunochromatographic tests
      for antigen detection performed directly on stool samples for its simplicity and
      rapid results may make them useful diagnostic elements in the context of primary
      care. METHOD: During October 2012 we selected all feces in which enteropathogenic
      bacteria are isolated from those received for stool culture in the laboratory of
      Microbiology of the University Hospital Virgen de las Nieves of Granada. After
      standard management of faeces samples and isolation of any enteropathogen, the
      commercial kits: Campy Leti, Ridaquick Campylobacterscreen and Salmonella Leti
      were tested for simultaneous research of Campylobacter and Salmonella antigens.
      Sensitivity and specificity were determined. RESULTS: Two hundred and thirty five
      stool samples were received in which 8 Salmonella enterica (7 B serogroup and 1 D
      serogroup), 7 Campylobacter jejuni, 4 Aeromonas hydrophila and 1 Yersinia
      enterocolitica were isolated. Campy Leti, Ridaquick Campylobacterscreen and
      Salmonella Leti presented a sensitivity of 100%, 100% and 75%, respectively.
      Specificities corresponded to 46%, 69% and 100%, respectively. CONCLUSION:
      Immunocromatographic tests can be useful for a first screening of enteropathogen
      in primary care.

PMID- 24940891
TI  - First clinical isolate in Europe of clindamycin-resistant group B Streptococcus
      mediated by the lnu(B) gene.
AB  - We characterize the mechanisms implicated in an unusual phenotype of resistance
      to macrolides-lincosamides (no halos of inhibition around clindamycin and
      lincomycin discs, and a 15 mm halo around erythromycin disc) in a Streptococcus
      agalactiae isolate recovered in Spain. The presence of macrolide or lincosamide
      resistance genes [erm(A), erm(B), erm(C), erm(T), mef(A), mrs(A), lnu(A), lnu(B),
      lsa(B), lsa(C) and vga(C)] was investigated by PCR and sequencing. The strain
      showed a resistant phenotype to erythromycin and clindamycin (MIC = 2 mg/L and
      MIC = 8 mg/L, respectively) and the presence of lnu(B) and mef(A) genes was
      demonstrated. Clinical microbiology laboratories should be aware of this unusual
      phenotype due to the association of two mechanisms mediated by lnu(B) and mef(A)
      genes. This constitute, to our knowledge, the first report of lnu(B) in S.
      agalactiae in human isolates in Europe. 

PMID- 24940892
TI  - Report of 38 cases of tracheobronchitis in non-immunocompromised patients with
      dual isolation of Aspergillus in lower respiratory tract samples.
AB  - INTRODUCTION: Aspergillus tracheobronchitis is an uncommon manifestation of
      Aspergillus infection. This study retrospectively analysed patients presenting
      tracheobronchitis among non-neutropenic/non-transplant adult patients with at
      least two valuable cultures of respiratory samples yielding Aspergillus spp. in
      Spanish hospitals. METHODS: Clinical records were retrospectively reviewed.
      Simple tracheobronchitis was considered when the bronchoscopy report described
      mucosal inflammation and mucus secretions and invasive tracheobronchitis when
      ulceration and pseudomembrane formation was reported. Cases were considered
      "proven" (histopathological confirmation) or "probable" aspergillar
      tracheobronchitis. RESULTS: A total of 38 cases of tracheobronchitis (26 simple,
      12 invasive) were identified, all considered probable aspergillar
      tracheobronchitis. Patients were elderly (89.5% patients were >= 65 years), males
      (76.3%), presented advanced COPD (GOLD III+IV in 81.3%) and heart insufficiency
      (55.3%), with higher APACHE II score in those with invasive tracheobronchitis
      (10.17 +/- 7.38 vs. 4.32 +/- 4.39, p=0.019). Up to 50% patients were taking
      steroids (accumulated doses >100 mg in 89.5% of them) and 34.2% antibiotics pre
      admission. Antifungals were administered to 60.5% patients (57.7% with simple and
      66.6% with invasive tracheobronchitis). Voriconazole was the most frequent
      antifungal (alone or in combination): 69.6% in the 23 treated patients (60.0%
      simple and 87.5% invasive tracheobronchitis). Mortality was 23.7% (15.4% in
      simple and 41.7% in invasive tracheobronchitis). CONCLUSIONS: The results of the
      present study suggest that aspergillar tacheobronchitis should be considered in
      the differential diagnosis of non-immunocompromised patients with deteriorating
      chronic airway limitation.

PMID- 24940894
TI  - [Epidemiology of Clostridium difficile-associated disease (CDAD) in Salamanca].
AB  - INTRODUCTION: Clostridium difficile infection is considered a major cause of
      nosocomial diarrhoea in developed countries and is increasingly becoming more
      important as an etiologic agent of community diarrhoea, also in patients without
      risk factors. METHOD: Beginning in May 2011, the aim of our study is to know the
      characteristics of patients suffering from C. difficile Associated Disease in
      Salamanca University Hospital, collecting their data in a survey conducted for
      this purpose. A case was defined as a patient with compatible clinical and
      positive microbiological diagnosis. RESULTS: After 18 months of study, 41 cases
      had been documented representing an incidence of 1.15 cases per 10,000 patient
      days. Patients were hospitalized (37) or health care associated (4), females
      (54%), age >= 65 years (56%) with prior antibiotic treatment (80%), most had
      diarrhea after the third day of admission, less than three weeks and without
      blood. Most were treated with metronidazole alone (78%), 19% with metronidazole
      and vancomycin, and the remaining percentage was resolved without treatment.
      Recurrences were about 20% and 7 (17%) died. CONCLUSIONS: The characteristics of
      our patients with C. difficile - associated disease are the same as those
      reported by other authors. Local surveillance is important in order to study the
      endemic and epidemic C. difficile infection. According to published
      epidemiological changes, we should be able to develop strategies from the
      Microbiology laboratories that will improve diagnosis of the disease.

PMID- 24940893
TI  - [Review of 1.250 episodes of skin and soft tissue infections attended at 49
      hospital emergency departments].
AB  - OBJECTIVE: To review the prevalence, clinical characteristics, approach and
      outcome of patients with skin and soft tissue infections (SSTI) evaluated at the
      Emergency Departments (ED) in Spain. METHODS: A descriptive multicenter cross
      sectional analysis in 49 ED of patients with SSTI. Data were collected for age,
      gender, comorbid conditions, risk factors for multiresistant pathogens, STTI
      type, sepsis criteria, microbiology, antibiotic treatment, destination and ED
      mortality. RESULTS: We documented 1,250 episodes (11% of all infections and 1.6%
      of all patients seen in ED), mean age 52 years (56% men) and the comorbidities
      and risk factors for major adverse outcomes were diabetes (15%), heart disease
      (12%), previous antibiotic therapy (10%) and solid malignancy (5%). 81% of STTI
      were nonnecrotizing, 3.3% had septic syndrome, in 65% of patients was not
      practised any microbiological study, and 16% had risk factors for infection for
      antibiotic-resistant gram-positive bacteria, with adequate empirical antibiotic
      therapy of 2.5%. 72% of patients were discharged home and 2 died. When comparing
      STTI discharged home respect those that were admitted, these latter were older
      patients with more comorbidities and risk factors for multidrug resistance,
      sepsis and there were more practised cultures (p < 0.05). CONCLUSIONS: The SSTI
      have a prevalence of 1.6%, representing 11% of visits to the ED for infection.
      44% of patients have comorbidity and 16% have risk factors for infection for
      resistant gram-positive pathogens and they were not made an appropriate
      antibiotic coverage.

PMID- 24940895
TI  - [Endovascular Campylobacter infections: report of two cases].

PMID- 24940896
TI  - [Spondylodiscitis by Streptococcus dysgalactiae subsp. equisimilis (group G)].

PMID- 24940897
TI  - [Pneumonia by Neisseria meningitidis: a case report].

PMID- 24940898
TI  - Correction: Antimicrobial stewardship in patients recently transferred to a ward
      from the ICU.
AB  - This paper is a corrigendum to the previously published paper: "Antimicrobial
      stewardship in patients recently transferred to a ward from the ICU" [Rev Esp
      Quimioter. 2014 Mar;27(1):46-50.] This corrigendum was prepared in order to
      correct some erroneous comments included in the discussion section. First, it
      should be pointed out that there could have been several suitable options for
      treating many infections and that, therefore, the word "inadequate" was not the
      most appropriate in this situation. In addition, some comments about the
      interpretation of microbiological results made by ICU physicians have been
      removed from the first article because this variable was not included in the
      study. Finally, another change made to the discussion was to clarify the ICU
      physicians' alleged low level of compliance with advice given by infectious
      disease specialists. This has been suggested in previous studies it cannot be
      substantiated when analyzing the results of the study. PURPOSE: Inappropriate use
      of antibiotics is an important health problem that is related to increasing
      bacterial resistance. Despite its relevance, many health institutions assign very
      limited resources to improving prescribing practices. An antimicrobial
      stewardship programme (APS) centred on patients discharged from the ICU could
      efficiently undertake this task. METHODS: During this six month study the main
      activity was performing a programmed review of antimicrobial prescriptions in
      patients transferred to the ward from the ICU. In the case of amendable
      antimicrobial treatment, a recommendation was included in the medical record.
      RESULTS: A total of 437 antimicrobial prescriptions for 286 patients were revised
      during a six month period and a total of 271 prescriptions (62%) in 183 patients
      were considered to be amendable. In most of these cases, treatment could have
      been reduced taking into consideration each patient's clinical improvement and
      their location in a hospital area with a lower risk of infection due to resistant
      bacteria. The most common advice was antimicrobial withdrawal (64%),
      antimicrobial change (20%) and switching to oral route (12%). Proposed
      recommendations were addressed in 212 cases (78%). There was no significant
      difference in adherence with respect to the type of recommendation (p=0.417).
      There was a 5% lower use of antibiotics during the year the study was conducted
      compared to the previous one. CONCLUSIONS: ASPs centred on patients discharged
      from the ICU may be an efficient strategy to ameliorate antimicrobial use in
      hospitals.

PMID- 24940900
TI  - Innate immunity induced by fungal beta-glucans via dectin-1 signaling pathway.
AB  - Mushrooms are a highly valuable source of substances that possess unique
      biological properties and medicinal efficacy. Medicinal mushrooms traditionally
      have been used to treat cancer, fungal infections, hypertension, diabetes,
      inflammation, and renal disorders. Medicinal mushrooms produce high-molecular
      weight beta-glucans, which have antitumor and antifungal activities that
      stimulate innate immunity. Innate immune cells express pattern recognition
      receptors (PRRs) such as dectin-1, Toll-like receptors, and mannose receptors on
      their cell surfaces. These PRRs recognize pathogens by binding to highly
      conserved pathogen-associated molecular patterns such as beta-glucan, mannan, and
      lipopolysaccharide. The immunomodulating activities of innate immune cells are
      augmented by the binding of beta-glucans to dectin-1 that is expressed by
      macrophages or dendritic cells. Upon binding beta-glucan, innate immune cells
      activate adaptive immune cells such as B and T lymphocytes or natural killer
      cells by secreting various cytokines such as interleukins (IL-4, IL-6) and tumor
      necrosis factor-alpha. Water-insoluble beta-glucans have stronger
      immunostimulating activities than their water-soluble counterparts. beta-glucans
      have antifungal activity that is similar to their anticancer activities and is
      mediated by binding to dectin-1, albeit by an unknown mechanism. In this review
      we discuss recent progress in understanding the mechanisms responsible for the
      antitumor activities of fungal beta-glucans that act through pathogen-associated
      molecular patterns and PRRs. 

PMID- 24940901
TI  - Telomerase inhibitory effects of medicinal mushrooms and lichens, and their
      anticancer activity.
AB  - Telomerase has been widely accepted as a cancer marker and a promising
      therapeutic target for novel anticancer drugs. The aim of this study was to
      investigate the in vitro telomerase inhibitory effects of mushrooms and their
      anticancer properties. The inhibitory effects of mushrooms and lichens against
      telomerase activity of HL-60 cells were systematically assessed using polymerase
      chain reaction based on assay of telomeric repeat amplification protocol.
      Telomerase inhibitory samples were further tested for antiproliferation effects
      against the gastric cell line SNU-1 using the MTT method. Ethyl acetate extract
      of Pleurotus ostreatus, ethyl acetate and water extracts of Lasiosphaera fenzlii,
      hexane extract of Strobilomyces floccopus, water extract of Sarcodon aspratus,
      and hexane, ethyl acetate, and water extracts from Umbilicaria esculenta showed
      strong positive telomerase inhibitory activity. Hexane extract of S. floccopus
      and water extracts from the edible lichen U. esculenta exhibited strong
      anticancer effects against SNU-1 cells through antiproliferation assay. The water
      extract of U. esculenta has a great potential to be developed into an anticancer
      agent that targets telomerase. 

PMID- 24940899
TI  - CD4+ T cell subset differentiation and avidity setpoint are dictated by the
      interplay of cytokine and antigen mediated signals.
AB  - CD4(+) T cell differentiation has been shown to be regulated by the cytokine
      milieu present during activation as well as peptide MHC levels. However, the
      extent to which these two important regulatory signals work in concert to shape
      CD4(+) T cell function has not been investigated. Using a murine OT-II transgenic
      TCR model of in vitro differentiation, we demonstrate that the ability of CD4(+)
      T cells to commit to a distinct lineage, i.e. Th1 vs. Th2 vs. Th17, is restricted
      by the amount of peptide antigen present in the stimulating environment. In
      addition, whether cells succumb to inhibitory effects associated with high dose
      antigen is dependent on the array of cytokine signals encountered. Specifically,
      stimulation with high dose antigen in Th1 or Th17 conditions promoted efficient
      generation of functional cells, while Th2 polarizing conditions did not. Finally,
      we found that the peptide sensitivity of an effector cell was determined by the
      combined actions of cytokine and peptide level, with Th1 cells exhibiting the
      highest avidity, followed by Th17 and Th2 cells. Together, these data show that
      the interplay of antigen and cytokine signals shape both the differentiation fate
      and avidity setpoint of CD4(+) T cells.

PMID- 24940902
TI  - Inhibitory effects of a polysaccharide extract from the Chaga medicinal mushroom,
      Inonotus obliquus (higher Basidiomycetes), on the proliferation of human
      neurogliocytoma cells.
AB  - This study aimed to investigate the inhibitory roles of a polysaccharide extract
      from Inonotus obliquus on U251 human neurogliocytoma cells cultured in vitro.
      After administering the polysaccharide extract from I. obliquus to U251 cells
      cultivated in vitro, methyl thiazolyl tetrazoliym assay was performed to measure
      the inhibitory effects of the extract on tumor cell proliferation. The expression
      of the apoptosis-related proteins Bcl-2 and caspase-3 were determined by Western
      blotting. Different concentrations of I. obliquus extract (25, 50, 100, 200, and
      500 ug/mL) were added to U251 cells at 24, 48, and 72 hours. Methyl thiazolyl
      tetrazoliym assay showed that the inhibition ratio increased with increased
      extract concentration and prolonged treatment duration. The I. obliquus extract
      sharply decreased the expression of Bcl-2 but dramatically increased the
      expression of caspase-3. This function was gradually enhanced with increased drug
      concentration and prolonged treatment duration. The I. obliquus extract can
      inhibit the proliferation of tumor cells. This inhibition function is closely
      related to the downregulation of Bcl-2 and the upregulation of caspase-3. 

PMID- 24940903
TI  - Dichlormethane extract of the jelly ear mushroom Auricularia auricula-judae
      (higher Basidiomycetes) inhibits tumor cell growth in vitro.
AB  - In this study, a dichloromethane fraction (DCMF) from 70% Auricularia auricula
      judae ethanol extract showed the highest level of antitumor activity compared to
      other solvent fractions (ethyl acetate, butanol, and water). The DCMF was found
      to have more potent antitumor activity against broncheoalveolar cancer (half
      maximal inhibitory concentration = 57.2 ug/mL) and gastric cancer cells (half
      maximal inhibitory concentration = 73.2 ug/mL) compared to the other solvent
      fractions, although all fractions inhibited the proliferation of the tumor cells
      in a dose-dependent manner. We further analyzed the DCMF composition by gas
      chromatography-coupled mass spectroscopy. Based on the results of this analysis,
      an antitumor active component (diazane) was identified in the DCMF. However, we
      found that diazane alone had a lower level of antitumor activity than the DCMF.
      These findings indicate that other unknown components of the DCMF also are
      responsible for the cytotoxic effects of DCMF against tumor cells.
      Semiquantitative reverse transcription polymerase chain reaction analysis
      demonstrated that DCMF induced cytotoxicity or tumor cell apoptosis as a result
      of the downregulation of Bcl-2 expression and p53 overexpression. Taken together,
      our study results demonstrated that the DCMF may be used as a functional additive
      for enhancing antioxidant activities and suppressing tumor growth in the body. 

PMID- 24940904
TI  - In vitro antitumor effects of the cold-water extracts of Mediterranean species of
      genus Pleurotus (higher Basidiomycetes) on human colon cancer cells.
AB  - The aim of this study was to evaluate whether the cold-water extracts of
      Pleurotus eryngii var. ferulae (CWE-Pef) and Pleurotus nebrodensis (CWE-Pn), 2 of
      the most prized wild and cultivated edible mushrooms, can affect the tumor
      phenotype of human colon cancer HCT116 cells. Our results showed that treatment
      with CWE-Pef and CWE-Pn resulted in a significant inhibition of the viability of
      HCT116 cells and promoted apoptosis, as also demonstrated by the increase of Bax
      to-Bcl-2 messenger RNA ratio. Moreover, we observed that both extracts were able
      to inhibit cell migration and to affect homotypic and heterotypic cell-cell
      adhesion. It also was found that treatment with CWE-Pef and CWE-Pn negatively
      modulated the phosphorylation of the protein tyrosine as well as the
      phosphorylation levels of extracellular signal-regulated kinase 1/2. In
      conclusion, the in vitro antitumor effects of CWE-Pef and CWE-Pn indicate that
      they can be considered as possible sources for new alternative therapeutic agents
      for cancer treatment. 

PMID- 24940905
TI  - Antioxidant capacity and polyphenolic content of dried wild edible mushrooms from
      Poland.
AB  - In this study 6 species of wild edible mushrooms were evaluated in terms of their
      total phenolic content and antioxidant activity using 1,1-diphenyl-2
      picrylhydrazyl radical and ferric reducing antioxidant power assay methods. The
      mushrooms, namely Armillaria mellea, Cantharellus cibarius, Lactarius deliciosus,
      Leccinum aurantiacum, Suillus luteus, and Boletus badius, were dried using both
      freeze drying and convection drying at 50 degrees C. The amounts of phenolic
      compounds varied from 3.0 +/- 0.1 to 12.8 +/- 0.4 mg gallic acid equivalents/g
      dry weight (for water extracts) and from 2.4 +/- 0.1 to 11 +/- 0.5 mg gallic acid
      equivalents/g dry weight (for ethanolic extracts). The species that presented the
      highest antioxidant potential were B. badius and S. luteus. The impact of hot-air
      drying on the antioxidant activity of water and ethanolic extracts was evaluated.
      We demonstrated that hot-air drying may have either a negative or positive
      influence on phenolics and antioxidant activity, depending on the mushroom
      species. However, a negative effect was more frequent. 

PMID- 24940906
TI  - Antimicrobial effect of the Lingzhi or Reishi medicinal mushroom, Ganoderma
      lucidum (higher Basidiomycetes) and its main compounds.
AB  - Mushrooms are considered one of the richest sources of natural antibiotics, and
      various species of them inhibit the growth of a wide diversity of microorganisms.
      Ganoderma lucidum, a well-known medicinal mushroom. has many pharmacological and
      biological activities including an antimicrobial effect, although few studies
      have investigated the antibacterial and antifungal effects of its purified
      compounds. The chemical structure of the purified compounds from the hexane
      fraction was elucidated as ergosta-7,22-dien-3beta-yl acetate, ergosta-5,7,22
      trien-3beta-yl acetate (isopyrocalciferol acetate), ergosta-7,22-dien-3-one,
      ergosta-7,22-dien-3beta-ol, and ergosta-5,7,22-trien-3beta-ol (ergostrol). In
      addition, the structure of ganodermadiol was demonstrated after purification from
      the chloroform fraction. The fractions inhibited Gram-positive bacteria and
      yeast, with minimum inhibitory concentration values of 6.25 mg/mL, but were
      ineffective against Gram-negative bacteria in the tested concentrations. The
      results were comparable for isolated compounds, whereas the mixture of ergosta
      7,22-dien-3beta-yl acetate and isopyrocalciferol acetate was weakly effective
      against Escherichia coli (minimum inhibitory concentration, 10 mg/mL). It could
      be assumed that the antimicrobial effect of crude fractions is the consequence of
      mixing triterpenoid and steroid compounds. 

PMID- 24940907
TI  - Proximate composition and functionality of the culinary-medicinal tiger sawgill
      mushroom, Lentinus tigrinus (higher Basidiomycetes), from the Philippines.
AB  - The proximate composition and functionality of Lentinus tigrinus were evaluated
      to establish and popularize this mushroom as functional food source. The
      evaluation of functionality focused on the antibacterial and hypoglycemic
      activities of the mushroom extracts. An acute single oral dose toxicity test in
      mice was used for its biosafety analysis. The pileus contained higher amounts of
      protein (25.9%), fat (2.1%), and ash (7.4%) and a higher energetic value (142.1
      kcal/100 g) than the corresponding stipe, whereas the stipe contained higher
      amounts of total carbohydrates (67.7%), which consist of dietary fiber (63.0%)
      and reducing sugar (4.7%), than the pileus. Biosafety analysis confirmed that L.
      tigrinus is an edible mushroom species; it was found to be toxicologically safe
      in imprinting control region mice. The administration of lyophilized hot water
      extract of the fruiting body (both 100 and 250 mg/ kg doses) to diabetic mice
      significantly lowered the glucose level by 26.9% in the third week, which was
      significantly comparable to the results of the antidiabetic agent glibenclamide,
      which was used as a positive control. In vitro antibacterial assay showed that
      the ethanolic extract of the fruiting body and the immobilized secondary mycelia
      had high antibacterial activities against Staphylococcus aureus but not on
      Escherichia coli. Combining its useful nutrients and significant biological
      properties, L. tigrinus can be considered a natural source of safe
      nutraceuticals. 

PMID- 24940908
TI  - Immunomodulatory effect of polysaccharides extracted from the medicinal mushroom
      Antrodia camphorata (higher Basidiomycetes) in specific pathogen-free chickens.
AB  - The immunomodulatory effect of polysaccharides extracted from mycelia of the
      medicinal mushroom Antrodia camphorata in submerged culture was studied in 100
      specific pathogen-free (SPF) chickens. The chickens were randomly divided into 2
      groups (50 per group). For the treated group, each kilogram of SPF chickens was
      fed 5 mg of A. camphorata extract (ACE) for 35 consecutive days. Chickens were
      killed on days 7, 14, 21, 28, and 35, and lymphocytes were separated from the
      blood, spleen, thymus, bursa, kidney, and pancreas of the chickens. The results
      showed that, compared to the control group, the immune organ indices (except for
      the thymus) were higher after 14 days (P < 0.05), and the contents of globulin in
      blood were significantly increased on the 21st day (P < 0.05). The most of
      biochemical indices did not significantly changed within 35 days of treatment.
      Moreover, the response of proliferation and the rates of positive T lymphocytes
      in blood were higher than in the control group (P < 0.05).The results presented
      herein indicate that ACE could enhance the immune functions of the organs in SPF
      chickens and could be an attractive application of nutraceuticals and
      pharmaceuticals. 

PMID- 24940910
TI  - Tumor plasticity interferes with anti-tumor immunity.
AB  - Since tumor cell plasticity was first shown to be crucial in tumor promotion and
      immune surveillance evasion, it has become an issue of intense investigation.
      Several mechanisms are associated with the acquisition of tumor cell plasticity
      and immune evasion, including loss of epithelial phenotype through epithelial-to
      mesenchymal transition (EMT). We discuss recent evidence revealing that tumor
      cell plasticity may lead to the emergence of immunoresistant variants and how the
      tumor microenvironment evolves to shape this plasticity. We argue that targeting
      carcinoma cell plasticity represents a novel strategy to better control the
      emergence of resistant variants and to ensure more effective cancer therapies. In
      this context, the design of innovative integrative immunotherapy approaches is
      warranted. 

PMID- 24940911
TI  - Regulation of chemokine expression in the tumor microenvironment.
AB  - Chemokines are chemotactic cytokines critical for homeostatic and inflammation
      induced trafficking of leukocytes during immune responses, hematopoesis, wound
      healing, and tumorigenesis. Despite three decades of intensive study of the
      chemokine network, the molecular mechanisms regulating chemokine expression
      during tumor growth are not well understood. In this review, we focus on the role
      of chemokines in both tumor growth and anti-tumor immune responses and on
      molecular mechanisms employed by tumor cells to regulate chemokine expression in
      the tumor microenvironment. Multiple mechanisms used by tumors to regulate
      chemokine production, including those revealed by very recent studies (such as
      DNA methylation or post-translational nitrosylation of chemokines) are discussed.
      Concluding the review, we discuss how understanding of these regulatory
      mechanisms can be used in cancer therapy to suppress tumor growth and/or to
      promote immune-mediated eradication of tumors. 

PMID- 24940913
TI  - Role of galectin-3 in the initial control of Leishmania infection.
AB  - Galectin-3 belongs to a family of galectins, evolutionarily conserved glycan
      binding proteins (lectins) that have recently attracted much attention as
      modulators in adaptive immune responses. Previously, galectins have been
      considered lectins that bind only to endogenous "self" glycans. Further,
      galectins are synthesized and stored in the cytosol, where there are virtually no
      glycan-containing proteins, raising doubts over the biological significance of
      their glycan binding capacity. As discussed in this review, with particular
      emphasis on the role of galectin-3 in the innate immune response against the
      protozoan parasite Leishmania, several recent studies have suggested that
      galectin-3 could recognize L. major-specific pathogen-associated molecular
      pattern and, in parallel, facilitate the infiltration of neutrophils to the
      infected sites that helps reduce the initial parasite burden once galectin-3 is
      released as a damage-associated molecular pattern. Thus, while further
      investigation is necessary, based on the current results, it could be proposed
      that galectin-3 can hinge two areas of the innate immune recognition system, DAMP
      and PAMP pathways in the early host responses against various pathogens. 

PMID- 24940914
TI  - Cardiovascular oxygen transport limitations to thermal niche expansion and the
      role of environmental Po2 in Antarctic notothenioid fishes.
AB  - The notothenioid fishes of the Southern Ocean possess some of the lowest upper
      thermal thresholds of any species and display a range of cardiovascular features
      that distinguish them from other fishes. Some species lack hemoglobin, and it has
      been posited that the inability to deliver sufficient oxygen at elevated
      temperature may in part determine upper thermal thresholds. Here, we provide an
      analysis of systemic O2 transport based on circulatory resistance, cardiac
      outputs, and cardiac power for three species of Antarctic fishes, including
      species that possess hemoglobin (Trematomus bernacchii, Pagothenia borchgrevinki)
      and a species lacking hemoglobin (Chaenocephalus aceratus) and that differ in
      their cardiovascular characteristics. This analysis supports the hypothesis that
      the mutation resulting in the lack of hemoglobin would be metabolically
      prohibitive at elevated temperatures. The analysis also suggests that such a
      mutation would be least detrimental to species with greater cardiac power outputs
      and lower total peripheral resistance. Decreased environmental Po2 has the
      greatest detrimental effect on the metabolic capacity in the species without
      hemoglobin. These data indicate that differences in cardiovascular
      characteristics of the notothenioid fishes place varying limits on thermal niche
      expansion in these species, but any significant increase in environmental
      temperature or decrease in environmental Po2 will prohibit maintenance of
      cardiovascular systemic O2 transport in all species. These data also suggest an
      evolutionary sequence of events such that a reduction in hematocrit, to reduce
      blood viscosity and resistance, was a first step in the invasion of low
      temperature habitats and loss of hemoglobin was followed by increased cardiac
      power output to achieve sustainable metabolic rates.

PMID- 24940915
TI  - The activity of carp muscle-specific creatine kinase at low temperature is
      enhanced by decreased hydrophobicity of residue 268.
AB  - Abstract The muscle-specific forms of creatine kinase in rabbit (RM-CK) and carp
      (M1-CK) exhibit different temperature-dependent functional properties. Replacing
      the glycine at residue 268 of RM-CK with asparagine increases the enzyme's
      activity at 10 degrees C. In this study, we investigated how hydrophobicity of
      residue 268 affects the biochemical properties of RM-CK and M1-CK at low
      temperature. We generated three mutants of both RM-CK and M1-CK: Asp268, Lys268,
      and Leu268. The secondary structures of these mutants were similar, as revealed
      by their circular dichroism spectra. Similar to the Asn268 mutants, the Asp268
      and Lys268 mutants of RM-CK and M1-CK exhibited higher specific activities at 10
      degrees C and pH 8.0. However, no such effect was observed for the RM-CK and M1
      CK Leu268 mutants. While in the presence of cryoprotectant (sucrose or
      trehalose), the activities of wild-type RM-CK and M1-CK mutant enzymes with a
      hydrophobic residue at 268 were higher, and the effect was more profound at pH
      8.0. It may be inferred that water molecules affect protein conformation around
      residue 268, thereby influencing protein stability at low temperature. 

PMID- 24940916
TI  - Latitudinal variation of freeze tolerance in intertidal marine snails of the
      genus Melampus (Gastropoda: Ellobiidae).
AB  - Abstract Low temperatures limit the poleward distribution of many species such
      that the expansion of geographic range can only be accomplished via evolutionary
      innovation. We have tested for physiological differences among closely related
      species to determine whether their poleward latitudinal ranges are limited by
      tolerance to cold. We measured lower temperature tolerance (LT50) among a group
      of intertidal pulmonate snails from six congeneric species and nine locales.
      Differences in tolerance are placed in the context of a molecular phylogeny based
      on one mitochondrial (cytochrome oxidase subunit I) and two nuclear (histone 3
      and a mitochondrial phosphate carrier protein) markers. Temperate species from
      two separate lineages had significantly lower measures of LT50 than related
      tropical species. Range differences within the temperate zone, however, were not
      explained by LT50. These results show that multiple adaptations to cold and
      freezing may have enabled range expansions out of the tropics in Melampus.
      However, northern range limits within temperate species are not governed by cold
      tolerance alone. 

PMID- 24940912
TI  - CD4 T-cell memory generation and maintenance.
AB  - Immunologic memory is the adaptive immune system's powerful ability to remember a
      previous antigen encounter and react with accelerated vigor upon antigen re
      exposure. It provides durable protection against reinfection with pathogens and
      is the foundation for vaccine-induced immunity. Unlike the relatively restricted
      immunologic purview of memory B cells and CD8 T cells, the field of CD4 T-cell
      memory must account for multiple distinct lineages with diverse effector
      functions, the issue of lineage commitment and plasticity, and the variable
      distribution of memory cells within each lineage. Here, we discuss the evidence
      for lineage-specific CD4 T-cell memory and summarize the known factors
      contributing to memory-cell generation, plasticity, and long-term maintenance. 

PMID- 24940917
TI  - The effects of dietary cholesterol on metabolism and daily torpor patterns in
      Siberian hamsters.
AB  - The concentrations of fatty acids in the diet influence torpor in numerous
      species of mammals. Much less is known, however, about the potential effects of
      other types of dietary lipids. One study demonstrated that increasing dietary
      cholesterol levels during fall feeding increased torpor bout length and also
      decreased minimum body temperatures during hibernation by chipmunks. Another
      hibernation study with ground squirrels revealed that the cholesterol contents of
      both the cerebral cortex and the microsomes were significantly greater during
      arousal episodes than during torpor bouts, suggesting that cholesterol plays a
      role in preserving brain function during torpor. We thus predicted that dietary
      cholesterol enhances daily torpor in mammals as well. We also predicted that the
      level of cholesterol found in mammalian brain tissues during daily torpor
      increases with that of the diet. These hypotheses were tested in a series of
      laboratory feeding and daily torpor experiments involving Siberian hamsters
      (Phodopus sungorus) maintained on semisynthetic diets varying only in cholesterol
      content. Hamsters that were maintained on diets with cholesterol contents of 0.3%
      2.5% during the summer entered winter daily torpor spontaneously, whereas those
      that were fed diets that contained no cholesterol did not. This is the first
      study to demonstrate the effects of a cholesterol-free diet on mammalian torpor.
      The presence of cholesterol in the summer diet also increased the level of
      cholesterol found in the brains of hamsters during the winter daily torpor
      period, but it did not during the summer. These findings support our hypotheses
      that dietary cholesterol is permissive for daily torpor in mammals and that it
      also increases brain cholesterol levels during the winter.

PMID- 24940918
TI  - How does flexibility in body composition relate to seasonal changes in metabolic
      performance in a small passerine wintering at northern latitude?
AB  - Abstract Small avian species wintering at northern latitudes typically show
      increases in basal metabolic rate (BMR) and maximal thermogenic capacity (Msum).
      Those are widely assumed to reflect changes in body composition, with enlargement
      of digestive and excretory organs resulting in elevated winter BMR and larger
      body muscles driving the increase in Msum. Using free-living black-capped
      chickadees (Poecile atricapillus) as our model species, we investigated seasonal
      changes in body composition and tested for relationships between mass variations
      of body organs and variability of both BMR and Msum. Our results confirmed the
      expected winter increase in mass of body muscles and cardiopulmonary organs
      (heart + lungs) and showed that 64% of the observed Msum variations throughout
      the year were explained by changes in these organs. In contrast, we found little
      support for an effect of the digestive organs (gizzard + intestines) on BMR
      seasonal changes. Instead, this variable was mainly influenced by variations in
      mass of body muscles and excretory organs (liver + kidney), explaining up to 35%
      of its variability. 

PMID- 24940919
TI  - Body-condition indices are repeatable across short, but not long, time periods in
      crimson finches Neochmia phaeton.
AB  - Abstract It is common in evolutionary ecology to interpret body-condition indices
      as indicators of individual quality, but this hypothesized relationship has been
      questioned and remains poorly validated. Here, we test one of the fundamental
      predictions of this condition-quality hypothesis, that relative-condition indices
      are repeatable within individuals, that is, that the index score of an individual
      relative to others is consistent over time. We sampled crimson finches (Neochmia
      phaeton) for seven commonly used condition indices and tested whether individual
      condition relative to conspecifics in the same context (e.g., breeding stage) was
      repeatable. We calculated the relative indices' repeatability across several
      temporal scales, from short (within breeding season) to long (more than 2 yr)
      time periods, as well as without consideration of timescale. Most relative
      condition indices were repeatable when sampled without consideration of
      timescale, all were repeatable within a short time period, and none were
      repeatable over the longest time period. This provides only partial support for
      the condition-quality hypothesis, because although relative-condition indices
      were generally repeatable, this was primarily attributed to short-term, instead
      of long-term, repeatability. Condition indices may be meaningful indicators of
      short-term survival or fitness potential, but our findings are inconsistent with
      the idea that condition indices are indicators of inherent individual quality. 

PMID- 24940920
TI  - Introduced and native congeners use different resource allocation strategies to
      maintain performance during infection.
AB  - Abstract Hosts can manage parasitic infections using an array of tactics, which
      are likely to vary contingent on coevolutionary history between the host and the
      parasite. Here we asked whether coping ability of congeners that differ in host
      parasite coevolutionary history differed in response to experimental infections
      with a coccidian parasite. House sparrows (Passer domesticus) and gray-headed
      sparrows (Passer griseus) are sympatric and ecologically similar, but house
      sparrows are recent colonizers of Kenya, the site of our comparison, whereas gray
      headed sparrows are native. We evaluated three variables as barometers of
      infection coping ability: vertical flight, pectoral muscle size, and fat score.
      We also measured routing of a dose of (13)C-labeled leucine, an essential amino
      acid, among tissues to compare resource allocation strategies in response to
      infection. We found that burden effects on performance were minimal in both
      species, but house sparrows maintained considerably higher burdens than gray
      headed sparrows regardless of exposure. House sparrows also had more exogeneous
      leucine tracer in all tissues after 24 h, demonstrating a difference in the way
      the two species allocate or distribute resources. We argue that house sparrows
      may be maintaining larger resource reserves to mitigate costs associated with
      exposure and infection. Additionally, in response to increased parasite exposure,
      gray-headed sparrows had less leucine tracer in their spleens and more in their
      gonads, whereas house sparrows did not change allocation, perhaps indicating a
      trade-off that is not experienced by the introduced species. 

PMID- 24940921
TI  - Loss of the ability to control right-to-left shunt does not influence the
      metabolic responses to temperature change or long-term fasting in the South
      American Rattlesnake Crotalus durissus.
AB  - Abstract In the undivided ventricle of noncrocodilian reptiles, the blood
      perfusing the systemic circulation is a controlled combination of oxygenated
      pulmonary blood, flowing from left to right across the heart, and relatively
      deoxygenated systemic blood, flowing from right to left. A clear inverse
      correlation has been experimentally established between metabolic demand and the
      magnitude of right-to-left cardiac shunt in several reptile groups. Unilateral
      left vagotomy renders the single effective pulmonary artery of the South American
      rattlesnake (Crotalus durissus) unable to adjust the magnitude of blood flow to
      the lung. This provides a unique model for investigation of the long-term
      consequences of abolition of the cardiac shunt in a squamate reptile.
      Rattlesnakes-vagotomized on the left or right side or sham operated-were exposed
      to long-term food deprivation or temperature change. Loss of control of the
      cardiac shunt following selective vagotomy did not change the progressive
      decrease in body mass or the onset of identifiable fasting stages. Resting
      metabolic rate and the increase in oxygen uptake measured during spontaneous or
      forced activity were also unchanged. The responses to reductions in temperature
      (from 30 degrees  to 20 degrees  or 15 degrees C) in adult snakes or juvenile
      snakes were similarly unaffected by vagal transection. These data support
      rejection of the hypothesis that adjustment of the cardiac shunt is central to
      the control metabolic rate in squamate reptiles. 

PMID- 24940922
TI  - Unique biochemical and mineral composition of whale ear bones.
AB  - Abstract Cetaceans are obligate aquatic mammals derived from terrestrial
      artiodactyls. The defining characteristic of cetaceans is a thick and dense lip
      (pachyosteosclerotic involucrum) of an ear bone (the tympanic). This unique
      feature is absent in modern terrestrial artiodactyls and is suggested to be
      important in underwater hearing. Here, we investigate the mineralogical and
      biochemical properties of the involucrum, as these may hold clues to the aquatic
      adaptations of cetaceans. We compared bioapatites (enamel, dentine, cementum, and
      skeletal bone) of cetaceans with those of terrestrial artiodactyls and
      pachyosteosclerotic ribs of manatees (Sirenia). We investigated organic,
      carbonate, and mineral composition as well as crystal size and crystallinity
      index. In all studied variables, bioapatites of the cetacean involucrum were
      intermediate in composition and structure between those of tooth enamel on the
      one hand and those of dentine, cementum, and skeletal bone on the other. We also
      studied the amino acid composition of the cetacean involucrum relative to that of
      other skeletal bone. The central involucrum had low glycine and hydroxyproline
      concentrations but high concentrations of nonessential amino acids, unlike most
      bone samples but similar to the tympanic of hippos and the (pachyosteosclerotic)
      ribs of manatees. These amino acid results are evidence of rapid bone
      development. We hypothesize that the mineralogical and amino acid composition of
      cetacean bullae differs from that of other bone because of (1) functional
      modifications for underwater sound reception and (2) structural adaptations
      related to rapid ossification. 

PMID- 24940923
TI  - [Imaging features of pacemaker and ICD-electrodes -- diagnostic imaging of
      pacemaker and ICD-probe placements].

PMID- 24940925
TI  - Technical Note: evaluation of the uncertainties in (choline + creatine)/citrate
      ratios measured by proton MR spectroscopic imaging in patients suspicious for
      prostate cancer.
AB  - The presented evaluation of the relative uncertainty (delta'CCC) of the (choline
      + creatine)/citrate (CC/C) ratios can provide objective information about the
      quality and diagnostic value of prostate MR spectroscopic imaging data. This
      information can be combined with the numeric values of CC/C ratios and provides
      metabolic-quality maps enabling accurate cancer detection and user-independent
      data evaluation. In addition, the prostate areas suffering most from the low
      precision of CC/C ratios (e. g., prostate base) were identified. 

PMID- 24940929
TI  - [GAST 2014 in Istanbul].

PMID- 24940931
TI  - [Interview -- "a clear positioning of interventional radiology"].

PMID- 24940930
TI  - [Egas Moniz (1874-1955)].

PMID- 24940932
TI  - [Dr. Fabian Bamberg, head of the MRI part of the study NAKO, interview -- "The
      National Cohort is a unique opportunity for radiology"].

PMID- 24940933
TI  - [Radiology & the law -- the obligation of monitoring the orthopedist regarding
      the written findings of the radiologist].

PMID- 24940934
TI  - Molecular Screening of Keratoconus Susceptibility Sequence Variants in VSX1,
      TGFBI, DOCK9, STK24, and IPO5 Genes in Polish Patients and Novel TGFBI Variant
      Identification.
AB  - PURPOSE: Keratoconus (KTCN) is a degenerative disorder of the eye that results in
      the conical shape and thinning of the cornea and is a leading cause for corneal
      transplantations. A number of studies suggest that genetic factors play a role in
      KTCN etiology. Some candidate gene variants have recently been shown to be
      associated with KTCN. The purpose of our study was to verify the role of VSX1,
      TGFBI, DOCK9, IPO5, and STK24 sequence variants in Polish KTCN patients. METHODS:
      Forty-two Polish patients with sporadic KTCN and 50 control individuals were
      enrolled into this study. Both affected and unaffected individuals underwent
      detailed ophthalmic examination. The mutations screening in the candidate genes
      was performed by the direct sequencing method. RESULTS: Analysis of VSX1, TGFBI,
      DOCK9, IPO5, and STK24 genes identified numerous sequence variants. Variants c.
      264_-255delGGGGTGGGGT, c.627 + 23G > A, c.809-6_809-5insT, and c.*200G > T in the
      VSX1 gene, and heterozygous c.1598G > A mutation (Arg533Gln) in exon 12 of TGFBI
      were detected for the first time in KTCN patients. Two known sequence variants of
      TGFBI c.1620T > C (Phe540Phe) and c.1678 + 23G > A were observed in KTCN patients
      and control individuals. The newly reported c.717 + 43A > G substitution in
      intron 7 of DOCK9 was identified in both KTCN patients and healthy individuals.
      CONCLUSIONS: Our investigation showed that KTCN-related sequence variants of
      analyzed genes were found in a very small proportion of the studied patients
      indicating that genes other than VSX1, TGFBI, DOCK9, IPO5, and STK24 are involved
      in the development and progression of KTCN in Polish patients. Our results
      support the hypothesis about the genetic heterogeneity of KTCN.

PMID- 24940935
TI  - From a Suspicious Cystic Pineal Gland to Pineoblastoma in a Patient with Familial
      Unilateral Retinoblastoma.

PMID- 24940936
TI  - Retinal Dysfunction in Patients with Congenital Fibrosis of the Extraocular
      Muscles Type 2.
AB  - INTRODUCTION: Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a
      distinct non-syndromic form of congenital incomitant strabismus secondary to
      orbital dysinnervation from recessive mutations in the gene PHOX2A. The phenotype
      includes bilateral ptosis, very large angle exotropia, ophthalmoplegia, and
      poorly-reactive pupils. Other than amblyopia, afferent visual dysfunction has not
      been considered part of CFEOM2; however, we have repeatedly observed non
      amblyopic subnormal vision in affected patients. The purpose of this study was to
      document this recurrent feature of the phenotype. METHODS: A retrospective case
      series (2002-2012). RESULTS: Eighteen patients (four families) were identified;
      all affected individuals had confirmed homozygous recessive PHOX2A mutations
      except one individual for whom genetic testing was not done because of multiple
      genetically confirmed family members. Age at assessment ranged from 5-62 years
      old (median 10 years old). All patients had decreased best-corrected visual
      acuity not completely explainable by amblyopia in both the preferred and non
      preferred eye. In those patients who had further ancillary testing, visual fields
      (five patients) and electroretinography (10 patients) confirmed abnormalities not
      ascribable to amblyopia. CONCLUSIONS: In addition to a distinct form of
      congenital incomitant strabismus, the phenotype of CFEOM2 includes subnormal
      vision consistent with retinal dysfunction. This could be the direct result of
      PHOX2A mutations or a secondary effect of orbital dysinnervation.

PMID- 24940937
TI  - Genotype/Phenotype Correlation in Primary Congenital Glaucoma Patients in the
      Lebanese Population: A Pilot Study.
AB  - BACKGROUND: The incidence of primary congenital glaucoma (PCG) varies among
      geographic regions and ethnic groups. The frequency of PCG in Lebanon and
      identification of disease-causing mutations have not been studied previously.
      PURPOSE: To investigate the role of Cytochrome P1B1 (CYP1B1) gene and Myocillin
      (MYOC) gene mutations in PCG in the Lebanese population and study possible
      genotype/phenotype correlations. METHODS: Patients with unilateral or bilateral
      PCG diagnosed at the American University of Beirut Medical Center and their first
      degree relatives (parents and siblings) were screened for CYP1B1 and MYOC
      mutations. Demographic and phenotypic characteristics were recorded. Phenotypic
      characteristics pertaining to disease severity and outcomes were compared.
      RESULTS: Eighteen Lebanese families (66 subjects) with at least one member
      affected with PCG were included in this study. Mutations in the CYP1B1 gene were
      detected in 6 families (33%). Five previously described mutations (p.R444Q;
      p.E229K; p.R469W; p.G61E; p.M1T) and one new single nucleotide deletion were
      identified (1793delC). Patients in whom CYP1B1 mutations were detected tended to
      have a more severe phenotype as evidenced by earlier age at diagnosis, higher
      rate of bilateral disease, and higher number of glaucoma surgeries than those in
      whom no CYP1B1 mutations were present. MYOC gene mutations were not detected in
      any patients. CONCLUSION: The rate of CYP1B1 mutations in Lebanese patients with
      PCG is lower than that reported in other Arab and Middle Eastern populations and
      suggests other genes are responsible for PCG in the remainder.

PMID- 24940938
TI  - Ion exchange and intercalation properties of layered double hydroxides towards
      halide anions.
AB  - A layered double hydroxide (LDH) obtained by the urea method, having an empirical
      formula [Zn(0.61)Al(0.39)(OH)2](CO3)(0.195).0.50H2O, has been converted into the
      corresponding chloride form [Zn(0.61)Al(0.39)(OH)2]Cl(0.39).0.47H2O by making the
      solid come into contact with a suitable HCl solution. The intercalation of the
      other halide anions (X(-) = F(-), Br(-), I(-)) via the Cl(-)/X(-) anion exchange
      has been attained and the respective anion exchange isotherms have been obtained
      with the batch method. The analysis of the isotherms indicates that the
      selectivity of LDH towards the halides decreases with the increase of the X(-)
      ionic radius, the selectivity order being F(-) > Cl(-)>= Br(-) > I(-). The CO3(2
      )/Cl(-) isotherm has also been reported to highlight the extraordinary
      selectivity of LDH towards carbonate anions. Samples taken from the isotherms at
      different exchange degrees were analyzed by X-ray diffraction, thermogravimetry
      and thermodiffractometry to obtain information about the ion exchange mechanism.
      The Cl(-)/Br(-) and the reverse Br(-)/Cl(-) exchanges occur with the formation of
      solid solutions, very likely because of the similar ionic radius of the
      exchanging anions. In contrast, in the Cl(-)/F(-) and Cl(-)/I(-) exchange, the co
      existence of the Cl(-) and F(-) (or I(-)) phases in the same sample was detected,
      indicating the occurrence of a first order phase transition, in which the
      starting phase is transformed into the final phase, as the process goes on. The
      variation of the interlayer distances of ZnAl-X intercalation compounds with the
      hydration degree has been interpreted with a structural model based on the
      nesting of the guest species into the trigonal pockets of the brucite-like layer
      surface. Rietveld refinements of the phases with the maximum F(-), Br(-) and I(-)
      content were also performed and compared with the above model, giving indications
      of the arrangement and order/disorder of the halide anions in the interlayer
      region.

PMID- 24940939
TI  - Electrical detection of nucleic acid amplification using an on-chip quasi
      reference electrode and a PVC REFET.
AB  - Electrical detection of nucleic acid amplification through pH changes associated
      with nucleotide addition enables miniaturization, greater portability of testing
      apparatus, and reduced costs. However, current ion-sensitive field effect
      transistor methods for sensing nucleic acid amplification rely on establishing
      the fluid gate potential with a bulky, difficult to microfabricate reference
      electrode that limits the potential for massively parallel reaction detection.
      Here we demonstrate a novel method of utilizing a microfabricated solid-state
      quasi-reference electrode (QRE) paired with a pH-insensitive reference field
      effect transistor (REFET) for detection of real-time pH changes. The end result
      is a 0.18 MUm, silicon-on-insulator, foundry-fabricated sensor that utilizes a
      platinum QRE to establish a pH-sensitive fluid gate potential and a PVC membrane
      REFET to enable pH detection of loop mediated isothermal amplification (LAMP).
      This technique is highly amendable to commercial scale-up, reduces the packaging
      and fabrication requirements for ISFET pH detection, and enables massively
      parallel droplet interrogation for applications, such as monitoring reaction
      progression in digital PCR. 

PMID- 24940940
TI  - Diuretics associated acute kidney injury: clinical and pathological analysis.
AB  - OBJECTIVE: In order to evaluate the clinical and pathological characteristics of
      diuretics associated acute kidney injury (AKI) and its management. METHODS: We
      performed a retrospective study including 131 cases that diagnosed as diuretics
      associated AKI from 1 January 1999 to 1 January 2010 in Ruijin Hospital
      affiliated to Shanghai Jiao Tong University. Drug applications and its related
      clinical, laboratory and histological data were collected. RESULTS: The male to
      female ratio was 2:1. The proportion of ages <20 years, 20-40 years, 40-60 years
      and >= 60 years were 6.9%, 17.6%, 27.5% and 48.1% respectively. Most patients
      (96.2%) had at least one complication of which chronic kidney disease (CKD)
      occurred most frequently (72 in 131, 55.0%). We divided all the patients to
      diuretic group (N=131) and non-diuretic group (N=185) based on diuretics history.
      We found patients in diuretic group had higher rates of CVD (38.9% vs. 18.4%),
      hypertension (42.0% vs. 29.2%), CKD (55.0% vs. 27.0%) and DM (17.6% vs. 4.3%)
      than non-diuretic group. Of 131 diuretics associated AKI, 36 cases (27.5%) were
      caused by diuretics only, 39 cases (29.8%) were caused by the combination of
      diuretics and other drugs like antibiotics, contrast media, ACEI or NSAIDs, and
      56 cases (42.7%) had other AKI risk factors such as operation, infection, acute
      heart failure or hepatorenal syndrome. In addition, our data suggested the
      severity of RIFLE classification and pathological injury of glomerular basement
      membrane was higher in large-dosage furosemide group (>=120 mg/d) than in low
      dosage group (<120 mg/d). The most common lesion induced by diuretics was
      vacuolar degeneration of tubular epithelial cell. Logistic regression analysis
      showed predictors of all-cause mortality were age, gender, RIFLE classification
      when AKI onset. Age and RIFLE classification were predictive factor of non
      complete recovery. CONCLUSION: This article firstly focuses on diuretics
      associated AKI, whose onset was related to aging, primary diseases and diuretic
      dosage. The combination of diuretics with other drugs such as antibiotics,
      contrast media, ACEI, NSAIDs, etc. would synergistically induced AKI. The
      pathological lesion of diuretics associated AKI may be mostly manifested vacuolar
      degeneration of tubular epithelial cell. Aging, gender, severity of RIFLE
      classification may be predictive factors of all-cause mortality of diuretics
      associated AKI.

PMID- 24940941
TI  - Ipsilateral intertrochantric and femoral head fracture without dislocation of the
      hip. Potentially misleading radiograph: a case report and review of literature.
AB  - BACKGROUND: Traumatic femoral head fracture without dislocation with ipsilateral
      intertrochanteric fracture is an extremely rare injury and has not been reported
      in the literature. CASE REPORT: We reported a case of simultaneous ipsilateral
      femoral head and intertrochantric fracture without dislocation of the hip in a 74
      year-old woman. The patient presented with a history of road traffic accident.
      Radiographs and computerised tomography scans revealed a right intertrochantric
      fracture and femoral head fracture without dislocation of the hip. CONCLUSIONS:
      The case was managed by uncemented modular bipolar arthroplasty using LINK
      reconstruction prosthesis. In the case report we described this unusual pattern,
      mechanism of injury, and management of such cases.

PMID- 24940943
TI  - Toward a human vaccines project.

PMID- 24940942
TI  - A randomized, endoscopist-blinded, prospective trial to compare the preference
      and efficacy of four bowel-cleansing regimens for colonoscopy.
AB  - OBJECTIVES: The superiority of conventional polyethylene glycol (PEG) solution
      over sodium picosulfate with magnesium citrate (SPMC) for bowel preparation
      remains controversial. Therefore, this study compared the efficacy, safety, and
      tolerability of different regimens of SPMC and PEG solution in Koreans, who
      consume a traditional high-fiber diet. MATERIALS AND METHODS: A total of 200
      outpatients undergoing elective colonoscopy were randomized into four groups
      receiving different bowel-preparation regimens in a prospective study: 4 L PEG in
      the morning on the day of colonoscopy, two 2 L split doses of PEG, split doses of
      2 SPMC sachets, and split doses of 3 SPMC sachets. Bowel cleansing efficacy was
      assessed based on the Ottawa bowel preparation scale and the Aronchick scale by
      endoscopists blinded to treatment, and patients filled out a questionnaire to
      determine satisfaction. RESULTS: There was no difference among groups with
      respect to bowel cleansing grade (Ottawa scale, p = 0.314). Patients in the SPMC
      groups were less likely to have abdominal fullness, pain, nausea, or vomiting
      than patients in the PEG groups (p < 0.05). Patients reported SPMC was more
      palatable than PEG. There were no significant differences among groups with
      respect to polyp detection rate. CONCLUSION: SPMC is as effective as conventional
      high-volume PEG-electrolyte solution in Korean patients. SPMC groups reported
      superior palatability and tolerability compared to PEG groups.

PMID- 24940944
TI  - New ingredients for brewing CD4(+)T (cells): TCF-1 and LEF-1.

PMID- 24940945
TI  - Chemokine 'grooming' by cLECs directs DC migration.

PMID- 24940946
TI  - Navigating double negatives: new pathways for regulating T(FH) differentiation.

PMID- 24940947
TI  - A gut reaction to IL-9.

PMID- 24940956
TI  - Editorial.

PMID- 24940957
TI  - Effectiveness and tolerability of schizophrenia treatment in Central and Eastern
      Europe: results after 1 year from a prospective, observational study (IC-SOHO).
AB  - Objective. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC
      SOHO) study is intended to complement smaller, shorter-term observational studies
      and randomised controlled clinical trials in providing information on the
      treatment of schizophrenia in various geographies that have not been well studied
      previously. Methods. Interim results after 12 months are presented for a subset
      of patients from eight Central and Eastern European (CEE) countries initiating or
      switching to olanzapine, risperidone, or typical antipsychotic monotherapy at
      Baseline (n=1387). Results. Patients initially prescribed olanzapine and
      risperidone experienced significantly greater improvements in a broad range of
      schizophrenia symptom domains compared with patients prescribed typicals.
      Furthermore, patients in the olanzapine group showed significantly greater
      improvements in overall and negative symptom domains compared with the
      risperidone group (all P<=0.05). While patients in the olanzapine group gained
      more weight than the other two groups, they had significantly lower odds of
      developing extrapyramidal symptoms, loss of libido, and sexual dysfunction.
      Patients initially prescribed olanzapine were also significantly less likely to
      have changed or added antipsychotics during 12 months of treatment compared with
      the risperidone and typicals groups. Conclusion. In this CEE sample,
      schizophrenia treatment outcomes after 12 months varied between patients
      initially prescribed different antipsychotics. 

PMID- 24940955
TI  - Three types of cytotoxic natural caged-scaffolds: pure enantiomers or partial
      racemates.
AB  - Two rare new natural products, the neocaged-xanthone pruniflorone T (1) and the
      rearranged caged-xanthone pruniflorone U (3), and the known caged-xanthone
      cochinchinone C (2) were isolated from the roots of Cratoxylum formosum ssp.
      pruniflorum. The unique structures of 1-3 were determined by analysis of NMR and
      X-ray diffraction data. The X-ray data of 1-3 revealed that they all exist with
      both enantiomers in their crystal packing. Separation of 1-3 by chiral HPLC led
      to the isolation of three pairs of enantiomers, (-)-1/(+)-1, (-)-2/(+)-2, and (-)
      3/(+)-3, and their absolute configurations were determined by analysis of single
      crystal X-ray diffraction and ECD spectroscopic data. A 1:1 mixture of 1 and 3
      showed potent in vitro cytotoxicity against an MCF-7 human breast cancer cell
      line with an IC50 value of 0.11 MUg/mL. 

PMID- 24940958
TI  - Personality, temperament and clinical scales in an Italian Plastic Surgery
      setting: what about body dysmorphic disorder?
AB  - Objective. Applications for aesthetic surgery may provide a good vantage point
      for assessing the psychiatric and personological aspects of subjects seeking
      cosmetic enhancement. Body dysmorphic disorder is relatively frequent (6-15%)
      among plastic surgery and dermatology patients. The aim of our study was to
      analyse the psychopathological profile, personality and temperament of 27
      patients requesting aesthetic surgery procedures and compare them with 21 normal
      controls. Methods. The Mini International Neuropsychiatric Interview Plus 5.0
      (MINIPLUS 5.0), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory, Y
      form (STAI), State-Trait Anger Expression Inventory (STAXI), Neo Five Factor
      Inventory (NEO-FFI), and Tridimensional Personality Questionnaire (TPQ) were
      used. Results. The dysmorphophobics in our sample (n=10) presented higher BDI,
      STAI and STAXI-state scores than the non-BDD patients (n=17) and controls (n=21);
      high rates of comorbidity, particularly with major depressive disorder, social
      phobia and obsessive-compulsive disorder; higher NEO-FFI scores for neuroticism
      and lower ones for extraversion, consciousness and openness to experience,
      compared with the control group. Significant differences in temperament were
      observed on the HA (Harm Avoidance) scale, with higher scores in the BDD than in
      the other two groups, particularly on the HA1 (anticipatory worry/uninhibited
      optimism) and HA4 (fatigability and asthenia/vigour) subscales. Conclusion. Our
      BDD patients were more depressed, more anxious and angrier with their present
      situation than controls. Although preliminary, our data are in keeping with the
      personality characteristics traditionally described in dysmorphophobic patients,
      considered to be sensitive, asthenic, shy, introverted, reserved and socially
      avoidant. 

PMID- 24940959
TI  - Effect of hormone replacement therapy on cognitive function in women with chronic
      schizophrenia.
AB  - Objective. The purpose of this investigation was to assess the cognitive effects
      of adjuvant hormone replacement therapy (HRT) when used to treat premenopausal
      women with chronic schizophrenia using an 8-week, double-blind, placebo
      controlled, randomized trial. Method. Women of childbearing age with chronic
      schizophrenia were recruited and randomized into placebo and HRT groups, the
      latter of which was administered 0.625 mg of conjugated oestrogen with 2.5 mg of
      medroxyprogesterone acetate daily. Each group contained 14 subjects. The
      principal outcome measure was a cognitive function assessment comprised of the
      following; the Immediate Visual Recognition Scale, List Recall Scale, Oral
      Fluency Test, Trail-Making Tests A and B, and Digit Symbol Test. Psychopathology
      was measured using the Scale for the Assessment of Negative Symptoms (SANS) and
      the Calgary Depression Scale for Schizophrenia. Extrapyramidal symptoms were
      evaluated using the Drug-Induced Extra-Pyramidal Symptoms Scale. Results.
      Improvements in SANS and in cognitive function as assessed using the List Recall
      Scale, Oral Fluency Test, and Trail-Making Test A, were significantly greater in
      the HRT group than in the placebo group. Conclusion. The results of this study
      suggest that short-term HRT is an effective adjuvant modality for improving
      cognitive function in women of childbearing age with chronic schizophrenia. 

PMID- 24940960
TI  - Minimising the risk of diabetes in patients with schizophrenia and bipolar
      disorder.
AB  - Objective. Patients with schizophrenia and bipolar disorder demonstrate a higher
      prevalence of abnormalities of glucose metabolism and are at risk of developing
      type 2 diabetes. Certain antipsychotics may unmask or exacerbate abnormalities of
      glucose metabolism. Type 2 diabetes is associated with considerable morbidity and
      mortality; therefore, minimising the risk of developing diabetes is of
      significant importance for the long-term health of patients. Methods. A search of
      studies published between January 1975 and November 2005 was performed. Results.
      Based on the evidence reviewed, clinical strategies are suggested for limiting
      the risk of developing diabetes in patients with schizophrenia or bipolar
      disorder. Epidemiological studies examining the risk of diabetes in patients
      treated with atypical antipsychotics are also examined in addition to mechanistic
      studies investigating how these effects might occur. Conclusion. An increased
      risk of diabetes with some atypical antipsychotics should not deter physicians
      from using these agents in patients with schizophrenia or bipolar disorder, but
      it is recommended that antipsychotic therapy be carefully selected in those
      patients at greatest risk of developing diabetes or metabolic syndrome.
      Appropriate management and regular monitoring of patients receiving
      antipsychotics should minimise the risk of patients with schizophrenia or bipolar
      disorder developing diabetes. 

PMID- 24940961
TI  - Excessive daytime sleepiness in psychiatry: a relevant focus for clinical
      attention and treatment?
AB  - Excessive daytime sleepiness is a feature of many general medical disorders and
      is associated with significant impairment in function and well-being. It has,
      however, received little attention in psychiatry although it may be a common and
      clinically important problem. The opinions of two expert groups, and a survey of
      the literature, were used to form views about the prevalence and clinical
      significance of excessive sleepiness in psychiatric populations. Issues relating
      to pharmacological treatment were also considered. Despite a scant evidence base,
      the conclusions are that excessive sleepiness may be a common and significant
      problem, and potentially amenable to treatment. However, clinician awareness is
      probably limited and there are opportunities for further research. 

PMID- 24940954
TI  - Neutrophils at work.
AB  - In this Review we discuss data demonstrating recently recognized aspects of
      neutrophil homeostasis in the steady state, granulopoiesis in 'emergency'
      conditions and interactions of neutrophils with the adaptive immune system. We
      explore in vivo observations of the recruitment of neutrophils from blood to
      tissues in models of blood-borne infections versus bacterial invasion through
      epithelial linings. We examine data on novel aspects of the activation of NADPH
      oxidase and the heterogeneity of phagosomes and, finally, consider the importance
      of two neutrophil-derived biological agents: neutrophil extracellular traps and
      ectosomes.

PMID- 24940962
TI  - The results of the Swiss observational study of the new, fast-dissolving
      mirtazapine formulation in depressed patients.
AB  - Objective. The purpose of the present study was to document the experience with
      the use of a new, fast-dissolving oral tablet (FDT, RemeronSolTab(r)) of
      mirtazapine, a NaSSA antidepressant, in the treatment of depressed patients in
      daily practice in Switzerland. Methods. It was an open, prospective collection of
      observations in a total of 1121 depressive patients (>18 years old, both sexes).
      The treatment duration was 8 weeks with assessments after the second and eighth
      week. Efficacy measures were CGI (seven points) and specific check-lists for the
      ratings of severity of anxiety and sleep disturbances. At the end of the trial
      the acceptance (eight-item questionnaire) of the new formulation was recorded
      too. Results. The results showed that there was highly significant (P<0.001) and
      rapid improvement of severity of depression, anxiety and sleep disturbances in
      the whole population. Subgroup analyses showed that the antidepressant efficacy
      was independent of gender, initial severity of depression or of the type of
      depression (first episode, recurrent, chronic depression). The majority of
      patients (80%) liked at least one of the properties of FDT and, out of 75% of
      patients having experience with conventional tablet, 50% stated to be better
      compliant with this new formulation. Conclusion. This report documents the
      antidepressant efficacy of mirtazapine FDT. The new formulation found good
      acceptance by the patients. The results also suggest a likelihood of improved
      compliance with the mirtazapine FDT. 

PMID- 24940963
TI  - Comparison of escitalopram and citalopram in outpatients with severe major
      depressive disorder: a prospective, naturalistic, 8-week study.
AB  - Objective. Escitalopram is a new selective serotonin reuptake inhibitor indicated
      for the treatment of major depressive disorder (MDD). The objective of this study
      is to examine its efficacy in the treatment of severe MDD compared with that of
      citalopram in daily practice. Method. A prospective, naturalistic, 8-week study
      was conducted involving 127 patients fulfilling DSM-IV criteria for severe MDD
      and having a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of
      at least 30. A full non-parsimonious logistic model, called the propensity score,
      was first defined to reduce bias associated with non-randomization. The primary
      efficacy analysis was the mean change from baseline to week 8 in MADRS score
      between the escitalopram and citalopram groups, after stratification on the
      propensity score. Other efficacy measurements consisted of the Clinical Global
      Impression of Severity and Improvement scales (CGI-S and CGI-I, respectively),
      response (defined as a reduction of at least 50% on MADRS from baseline to week
      8) and remission rates (defined as MADRS <= 12 at week 8), after adjustment on
      propensity score for escitalopram use. Results. A total of 67 escitalopram
      treated patients and 60 citalopram-treated patients were enrolled in this study.
      Escitalopram reduced mean MADRS total score at week 8 compared with citalopram (
      23.5 vs. -17.5; P<0.001). The effect of escitalopram was consistently greater
      than that of citalopram on the CGI scales. Escitalopram-treated patients were
      also more likely to respond to treatment (79.4 vs. 44.0%; P<0.001), and remission
      rates were also in favour of escitalopram (56.9 vs. 11.2%, P<0.001). Analysis of
      safety data showed better tolerability of escitalopram than that of citalopram.
      Conclusion. Using adequate methodology to reduce biases due to non-randomization,
      this study indicates better efficacy and tolerability of escitalopram versus
      citalopram in severe MDD outpatients. 

PMID- 24940964
TI  - Clinical experience with atypical antipsychotics in an acute inpatient unit:
      focus on quetiapine.
AB  - Objective. To evaluate dosing and time to efficacy of atypical antipsychotics in
      an acute inpatient unit. Methods. Admissions during 2001 were reviewed. Patients
      primarily treated with an atypical antipsychotic (including those simultaneously
      commenced on a mood stabiliser and/or antidepressant or receiving
      benzodiazepines) were evaluated. Non-acute patients, those without medical
      records or transferred to other hospitals were excluded. Medication details were
      noted. Results. A total of 137 patients were evaluated; 56 (41%) had received
      risperidone, 38 (28%) olanzapine, and 37 (27%) quetiapine. Mean doses (mg/day) at
      discharge were risperidone 4.1+/-2.3, olanzapine 22.5+/-10.2, quetiapine 576+/
      472. Dose ranges (mg/day) were risperidone 0.5-12, olanzapine 5-40, quetiapine 50
      1800. No differences between atypicals in time to efficacy/concomitant
      anticholinergics/mood stabilisers were observed. Benzodiazepine use was more
      frequent with risperidone and olanzapine than quetiapine. No serious side effects
      with any drug were noted. Quetiapine was rapidly titrated in 20 patients (up to
      400 mg on Day 1). In 18 of these, acute disturbance was controlled. Two patients
      were switched for lack of efficacy, one due to persistent tachycardia, and five
      for concern about early postural hypotension. Conclusion. These data provide
      further evidence concerning dose and dose range of atypicals required for optimal
      clinical outcome. More rapid initiation with quetiapine may be of benefit to some
      patients in the acute inpatient setting. 

PMID- 24940965
TI  - A benzisothiazole derivative and antipsychotic agent, perospirone, for
      augmentation of selective serotonin reuptake inhibitors (SSRIs) in refractory
      obsessive-compulsive disorder (OCD): two patient case series.
AB  - Even though selective serotonin reuptake inhibitors (SSRIs) are the mainstay of
      pharamacological treatment for obsessive-compulsive disorder (OCD), as many as
      40% of patients do not have an adequate response to these medications. For such
      SSRI-refractory patients, the augmentation of SSRIs with new-generation
      antipsychotics that modulate both 5-HT and DA systems has recently been proven
      effective in controlled augmentation studies. The benzisothiazole derivative
      perospirone is a new serotonin 5-HT2 and dopamine D2 antagonist available in
      Japan for the treatment of schizophrenia. As its unique property, perospirone
      also exhibits 5-HT1A agonistic action. We present two SSRI-refractory OCD
      patients who showed little improvement with adequate trials of SSRI monotherapy,
      but exhibited significant improvement in their OCD symptoms after the addition of
      perospirone to ongoing SSRI treatment. The cases suggest that perospirone
      augmentation may be an effective and well-tolerated strategy for SSRI-refractory
      OCD patients. Controlled studies are required to further confirm the efficacy and
      tolerability of perospirone augmentation for treatment-resistant OCD. 

PMID- 24940966
TI  - Hypericum-induced mood disorder: switch from depression to mixed episodes in two
      patients.
AB  - Objective. To point out the danger of worsening mood disorders with the use of
      hypericum. Methods. Longitudinal clinical observation of two cases treated with
      hypericum. Results. The two patients underwent mixed episodes following hypericum
      treatment. One of them needed hospitalization for suicidal risk. Conclusion.
      Caution is warranted in the use of hypericum in depressed patients with hidden
      bipolarity. Patients should be informed that hypericum may induce manic symptoms,
      increase cycling of mood states, or worsen the depressive state. 

PMID- 24940967
TI  - Pathological fantasy friend phenomenon.
AB  - Fantasy friend or imaginary companions is usually regarded as normal phenomenon
      and commonly seen in children. The index case is presented for highlighting the
      pathological nature of fantasy friend phenomenon, role of psychological, social
      and cultural factors in its genesis and its course. Onset and persistence of this
      phenomenon throughout adolescence, its longer duration and non-recognition of its
      imaginary component by the patient indicates its pathological nature. The patient
      developed schizophrenia after experiencing this phenomenon for 12-13 years. It is
      concluded that pathological fantasy friend phenomenon may carry risk of
      schizophrenia if continued without any intervention for longer duration. Hence,
      there is a need to identify and intervene early in such kind of cases. The
      findings of this case report needs to be corroborated by other case reports or
      studies. 

PMID- 24940968
TI  - Blood transfusion from a Hb E trait donor can affect beta-thalassemia diagnosis.
AB  - A subject with Hb E (HBB: c.79G > A) trait is asymptomatic and can become a blood
      donor. However, a blood transfusion from a Hb E trait donor can affect beta
      thalassemia (beta-thal) diagnosis. Blood samples from three Thai women were sent
      to the Associated Medical Sciences (AMS) Clinical Service Center, Chiang Mai,
      Thailand, for thalassemia diagnosis. Their Hb A2 levels, analyzed by high
      performance liquid chromatography (HPLC), were higher than 4.0%, thus they were
      diagnosed to have beta-thal. However, elevated Hb A2 levels in these patients
      were not certain because the Hb A2 levels analyzed at the initial hospitalization
      and follow-up were controversial. In addition, there were some cases shown to
      have controversy between the increased Hb A2 level and red cell indices. The
      blood transfusion history was confirmed and hemoglobin (Hb) analysis was
      reanalyzed by capillary electrophoresis (CE). On the CE electrophoregram, Hb A2
      levels were observed to be normal and Hb E peaks were present. Therefore, to rule
      out misdiagnosis and unnecessary genetic counseling, Hb analysis should be
      performed on the recipient prior to blood transfusions. Moreover, CE has a high
      efficiency to prevent the misinterpretation of Hb analysis in patients who
      receive blood transfusions from a donor carrying Hb E.

PMID- 24940969
TI  - John H. Weisburger, Ph.D., M.D.h.c., cancer research and prevention scientist:
      September 15, 1921-February 17, 2014.

PMID- 24940970
TI  - A combination of the "pillaring" strategy and chiral induction: an approach to
      prepare homochiral three-dimensional coordination polymers from achiral
      precursors.
AB  - Utilizing enantiopure camphorsulfonic acid as a chiral induction agent, 3D
      homochiral complexes were obtained from achiral 2D layers and MoO4(2-) pillars.
      This methodology combines the "pillaring" strategy with chiral induction,
      providing a new way to synthesize homochiral 3D coordination polymers
      intentionally from achiral precursors. 

PMID- 24940972
TI  - What young men do.

PMID- 24940973
TI  - The anhedonias: Clinical and neurobiological aspects.
AB  - During the last 30 years there has been renewed clinical interest in the state of
      'lack of pleasure' (anhedonia) seen in conditions such as schizophrenia and
      depression. In spite of some important work, confusion still remains about the
      term, behaviours and explanatory concepts pertaining to anhedonia. This paper
      reviews the clinical and basic scientific studies that throw light on this
      interesting clinical phenomenon and then presents a new model of anhedonia which
      can be tested empirically and should facilitate research in this field. 

PMID- 24940974
TI  - Twenty years of cholinergic intervention in Alzheimer's disease: A tale of
      disappointment and ultimate confidence.
AB  - The authors present an overview of drugs that operate on the basis of the
      cholinergic hypothesis, either currently available for the palliative treatment
      of Alzheimer's disease or in the later stages of clinical development. Of the
      many conceivable strategies that are being exploited, only inhibitors of
      acetylcholinesterase have been shown to have sufficient therapeutic potential and
      manageable side-effect profiles to be turned into broadly acknowledged drugs.
      These compounds, and others based on the modulation of cholinergic
      neurotransmission, are discussed and a differentiation of their clinical
      potential is attempted. 

PMID- 24940975
TI  - Alzheimer's disease and the aluminium connection: A literature review.
AB  - This review explores the different areas of research that, over the past 35
      years, have provided grounds for linking Alzheimer's disease and aluminium.
      However, in spite of the growing evidence, exposure to aluminium as a risk factor
      is yet to be confirmed. The evidence is discussed under four headings: evidence
      from brain aluminium studies; evidence from aluminium uptake studies; evidence
      from aluminium-related neurodegenerative conditions; and evidence from chronic
      aluminium exposure studies: aluminium in drinking water, and by occupational
      exposure. 

PMID- 24940976
TI  - Therapeutic models for somatoform disorders in liaison psychiatry.
AB  - Somatoform disorders are usually supposed to be seen in the clinical field of
      consultation-liaison (C-L) psychiatry. This study reviewed medical records of
      physically ill inpatients who were also treated by psychiatrists for concurrent
      psychiatric illnesses during a 5-year period. The prevalence of somatoform
      disorders was 40 out of 1581 cases (2.5%), which was unexpectedly low. From the
      perspective of C-L psychiatry, the authors propose three therapeutic models for
      somatoform disorders: 1. physician-oriented with psychiatric advice; 2.
      psychiatrist-oriented; and 3. cooperative physician/psychiatrist-oriented. The
      third model is particularly recommended because the patient can undergo physical
      examinations until the relationship between somatic complaints and psychosocial
      factors is recognized. Moreover, the psychiatrist can build an alliance with a
      patient, while the patient completes a 'testing phase' to determine whether the
      psychiatrist can be relied on or not. The third model is useful as such and can
      be used at least in the initial phase. 

PMID- 24940977
TI  - Reboxetine in the treatment of depression: Early clinical experience in the UK.
AB  - The potential efficacy and tolerability of new antidepressants can best be
      assessed through randomized controlled trials (RCTs). However, the patient
      population in antidepressant studies is a highly selected group, so the results
      from such studies may not be applicable to routine clinical practice. This paper
      describes a questionnaire survey of senior psychiatrists in the UK aimed at
      evaluating early clinical experience with reboxetine, a new, selective
      noradrenaline re-uptake inhibitor (selective NRI) recently introduced in the UK
      for the treatment of depression. Psychiatrists were asked for details of their
      experience with reboxetine in depression, illustrated with representative case
      histories. The spontaneous adverse events reported to the Medicines Control
      Agency (MCA) were also reviewed. Information was collected on over 250 patients,
      50% of whom had responded sub-optimally to previous physical treatments for this
      current episode; over 50% had co-morbid psychiatric disorders, and 29.1% had
      coexisting physical illness. Most of the patients were treated with 8 mg/day of
      reboxetine. The overall clinical response to reboxetine, as judged by the
      treating doctor, was considered 'good' in over 65% of patients. Three-quarters of
      them showed 'good/very good' improvement in their symptoms; the same proportion
      achieved a 'good/very good' improvement in activities of daily living. Two-thirds
      of patients did not report any troublesome side-effects, the profile being
      consistent with that seen in RCTs. Analysis of spontaneous adverse events
      reported to the MCA has not as yet revealed any surprises. Early clinical
      experience with reboxetine in routine practice is encouraging. Efficacy,
      tolerability and simple dosing appear to be particular benefits to patients.
      Consistent with data from RCTs involving reboxetine, recovery of function
      accompanies symptomatic improvement, which may be related to the selective
      effects of the drug on noradrenaline. 

PMID- 24940978
TI  - The prescribing practices of olanzapine in a psychiatric hospital in Britain.
AB  - The aim of this study was to review the prescribing practices at St Andrew's
      Hospital of the atypical antipsychotic drug olanzapine. Forty-one patients were
      treated with olanzapine by nine preservers during a 9-month study period. Two
      distinct categories of patients received the drug. Category A (n=30) patients
      were long-stay tertiary referrals, predominantly male and with a diagnosis of
      schizophrenia. For this group olanzapine was prescribed in high doses and half
      had additional anfipsjchotic medication; 17 patients (57%) improved but 30% were
      withdrawn from treatment. Category B (n=11) patients were acute admissions,
      younger, had a variety of diagnoses and were prescribed olanzapine at lower
      doses. All Category B patients improved after starting olanzapine and there were
      no dropouts. The presenters consistently reported positive experiences about the
      use of olanzapine. 

PMID- 24940979
TI  - A comparison between the OPCS and coroner's data on suicide and undetermined
      deaths in an English Health District.
AB  - Data on suicide and undetermined deaths were collected for the Rotherham Health
      District in South Yorkshire, United Kingdom, for a ten-year period from the
      Coroner's Office and the Office of Population Censuses and Surveys (OPCS).
      Certain discrepancies were detected. These included a delay in the recording of
      deaths by the OPCS, the selective inclusion of coroner's open verdict deaths, and
      the inclusion within the suicide figures of some deaths found later to be caused
      through homicide, as well as other minor inaccuracies. The reasons for the
      differences in the two sets of data and the implications for the accuracy of
      suicide statistics both nationally and locally are briefly discussed. 

PMID- 24940980
TI  - Depression rating scales can be related to each other by simple equations.
AB  - We present evidence that scores on the Montgomery, Hamilton and Beck depression
      scales are strongly intercorrelated and can be equated to each other. These
      scales were administered on 107 occasions to patients with major depression. The
      correlations between scores on each scale were much higher than has been
      previously reported and, furthermore, the relationships were always well
      described by a linear function. The close correlations could not be explained by
      rater biases. We were able to provide validation data for two of the rating
      scales, demonstrating that our simple models generalize well to a novel dataset.
      The knowledge that there is a robust relationship between the three scales has
      practical value for both clinicians and researchers. 

PMID- 24940981
TI  - Abnormal patterns of cerebral glucose metabolism in a pair of monozygotic twins
      with recent onset schizophrenia.
AB  - An F-18-FDG-PET study of a pair of monozygotic twins with recent-onset
      schizophrenia revealed a higher index of metabolic asymmetry (IA) in the medial
      and posterior thalamus in both cases. Some questions regarding the influence of
      neuroleptic treatment and handedness on metablic patterns and the role of the
      thalamus in schizophrenia are discussed in the light of recent studies. 

PMID- 24940982
TI  - Elevated plasma paroxetine concentrations in a patient treated with a combination
      of paroxetine and pindolol.
AB  - Paroxetine and pindolol have been used in combination to augment the
      antidepressant response of SSEIs. The rationale given involves the prevention of
      a negative feedback inhibition of serotonergic neurons but few studies have
      addressed potential pharmacokinetic interactions. This paper reports on elevated
      plasma paroxetine concentrations in a 37-year-old depressed woman following the
      introduction of pindolol. This case study supports the possibility of competitive
      drug-drug interactions in combinations of paroxetine and pindolol. 

PMID- 24940983
TI  - Rhabdomyolysis leading to acute renal failure following administration of
      neuroleptic medication.
AB  - The case of a 48-year-old man who developed rhabdomyolysis, without the features
      of neuroleptic malignant syndrome, following the administration of neuroleptics
      is described. Possible mechanisms for this development, and methods of detection,
      are discussed. 

PMID- 24940984
TI  - A patient who changed my practice.
AB  - An encounter with a patient with Huntington's Disease gave rise to the beginning
      of a holistic biopsychosocial approach to behavioural expressions of
      neurodegenerative diseases. Such an approach should be in the context of
      unconditional positive regard for patients. 

PMID- 24940988
TI  - Clavibacter michiganensis subsp. michiganensis Vatr1 and Vatr2 transcriptional
      regulators are required for virulence in tomato.
AB  - The plant pathogen Clavibacter michiganensis subsp. michiganensis is a gram
      positive bacterium responsible for wilt and canker disease of tomato. Although
      disease development is well characterized and diagnosed, molecular mechanisms of
      C. michiganensis subsp. michiganensis virulence are poorly understood. Here, we
      identified and characterized two C. michiganensis subsp. michiganensis
      transcriptional regulators, Vatr1 and Vatr2, that are involved in pathogenicity
      of C. michiganensis subsp. michiganensis. Vatr1 and Vatr2 belong to TetR and MocR
      families of transcriptional regulators, respectively. Mutations in their
      corresponding genes caused attenuated virulence, with the Deltavatr2 mutant
      showing a more dramatic effect than Deltavatr1. Although both mutants grew well
      in vitro and reached a high titer in planta, they caused reduced wilting and
      canker development in infected plants compared with the wild-type bacterium. They
      also led to a reduced expression of the ethylene-synthesizing tomato enzyme ACC
      oxidase compared with wild-type C. michiganensis subsp. michiganensis and to
      reduced ethylene production in the plant. Transcriptomic analysis of wild-type C.
      michiganensis subsp. michiganensis and the two mutants under infection-mimicking
      conditions revealed that Vatr1 and Vatr2 regulate expression of virulence
      factors, membrane and secreted proteins, and signal-transducing proteins. A 70%
      overlap between the sets of genes positively regulated by Vatr1 and Vatr2
      suggests that these transcriptional regulators are on the same molecular pathway
      responsible for C. michiganensis subsp. michiganensis virulence.

PMID- 24940989
TI  - Phytophthora sojae TatD nuclease positively regulates sporulation and negatively
      regulates pathogenesis.
AB  - During pathogenic interactions, both the host and pathogen are exposed to
      conditions that induce programmed cell death (PCD). Certain aspects of PCD have
      been recently examined in eukaryotic microbes but not in oomycetes. Here, we
      identified conserved TatD proteins in Phytophthora sojae; the proteins are key
      components of DNA degradation in apoptosis. We selected PsTatD4 for further
      investigation because the enzyme is unique to the oomycete branch of the
      phylogenetic tree. The purified protein exhibited DNase activity in vitro. Its
      expression was upregulated in sporangia and later infective stages but
      downregulated in cysts and during early infection. Functional analysis revealed
      that the gene was required for sporulation and zoospore production, and the
      expression levels were associated with the numbers of hydrogen-peroxide-induced
      terminal dUTP nick end-labeling-positive cells. Furthermore, overexpression of
      PsTatD4 gene reduced the virulence in a susceptible soybean cultivar. Together,
      these data suggest that apoptosis may play different roles in the early and late
      infective stages of P. sojae, and that PsTatD4 is a key regulator of infection.
      The association of PsTatD4 and apoptosis will lay a foundation to understanding
      the basic biology of apoptosis and its roles in P. sojae disease cycle. 

PMID- 24940990
TI  - The photosystem II oxygen-evolving complex protein PsbP interacts with the coat
      protein of Alfalfa mosaic virus and inhibits virus replication.
AB  - Alfalfa mosaic virus (AMV) coat protein (CP) is essential for many steps in virus
      replication from early infection to encapsidation. However, the identity and
      functional relevance of cellular factors that interact with CP remain unknown. In
      an unbiased yeast two-hybrid screen for CP-interacting Arabidopsis proteins, we
      identified several novel protein interactions that could potentially modulate AMV
      replication. In this report, we focus on one of the novel CP-binding partners,
      the Arabidopsis PsbP protein, which is a nuclear-encoded component of the oxygen
      evolving complex of photosystem II. We validated the protein interaction in vitro
      with pull-down assays, in planta with bimolecular fluorescence complementation
      assays, and during virus infection by co-immunoprecipitations. CP interacted with
      the chloroplast-targeted PsbP in the cytosol and mutations that prevented the
      dimerization of CP abolished this interaction. Importantly, PsbP overexpression
      markedly reduced virus accumulation in infected leaves. Taken together, our
      findings demonstrate that AMV CP dimers interact with the chloroplast protein
      PsbP, suggesting a potential sequestration strategy that may preempt the
      generation of any PsbP-mediated antiviral state. 

PMID- 24940987
TI  - Extracellular signal-regulated kinase 5 and cyclic AMP response element binding
      protein are novel pathways inhibited by vandetanib (ZD6474) and doxorubicin in
      mesotheliomas.
AB  - Malignant mesothelioma (MM), lung cancers, and asbestosis are hyperproliferative
      diseases associated with exposures to asbestos. All have a poor prognosis; thus,
      the need to develop novel and effective therapies is urgent. Vandetanib (Van)
      (ZD6474, ZACTIMA) is a tyrosine kinase inhibitor that has shown equivocal results
      in clinical trials for advanced non-small cell lung cancer. However, tyrosine
      kinase inhibitors alone have shown no significant clinical activity in phase II
      trials of patients with unresectable MM. Using epithelioid (HMESO) and
      sarcomatoid (H2373) human MM lines, the efficacy of tumor cell killing and
      signaling pathways modulated by Van with and without doxorubicin (Dox) was
      examined. Van alone reduced total cell numbers in HMESO MM and synergistically
      increased the toxicity of Dox in HMESO and H2373 cells. Most importantly, we
      identified two novel cell survival/resistance pathways, ERK5 and cyclic AMP
      response element binding protein (CREB), that were inhibited by Van and Dox.
      After silencing of either ERK5 or CREB, significant decreases in cell numbers in
      the Dox-resistant sarcomatoid H2373 line were observed. Results suggest that a
      plethora of cell signaling pathways associated with cell survival are induced by
      Dox but inhibited by the addition of Van in MM. Data from our study support the
      combined efficacy of Van and Dox as a novel approach in the treatment of MM that
      is further enhanced by blocking ERK5 or CREB signaling cascades.

PMID- 24940991
TI  - Direction-dependent freezing of diamagnetic colloidal tracers suspended in
      paramagnetic ionic liquids.
AB  - The dynamic behavior of an inverse ferrofluid consisting of diamagnetic,
      spherical silica particles suspended in the paramagnetic ionic liquid
      (EMIm)2[Co(NCS)4] is investigated by means of x-ray photon correlation
      spectroscopy in the presence of an external magnetic field. Dipole-dipole
      interactions between the diamagnetic holes in the paramagnetic continuum of the
      suspending medium induce a direction-dependence of the diffusive motion of the
      colloidal particles: due to a magnetic repulsion perpendicular to the direction
      of an external field the diffusive motion of the colloidal particles is
      selectively frozen in this direction. 

PMID- 24940992
TI  - Revised Bi/M layered oxo-sulfate (M = Co, Cu): a structural and magnetic study.
AB  - The combination of oxo-bismuthite slabs with counter oxo-anions main often leads
      to a series of layered Sillen-related compounds. For electroneutrality, it is
      convenient that the structure incorporates aliovalent cations such as
      Bi(3+)/M(2+) ions that could be confined either in the Bi/O slabs or in the
      interleave. In the case of SO4(2-) oxo-anions, only two compounds have been
      reported for M = Co, Cu, while interesting magnetic topologies emerge in absence
      of any prior characterization. Our reinvestigation of these systems using crystal
      growth in Bi2O3 flux led to the full structural characterization of
      [Bi2CoO3](SO4) (I) and [Bi6.2367Cu1.6O8](SO4)3 (II), which both exhibit pleated
      [Bi/M/O] slabs running in doubled cells comparatively to previous reports. (I)
      shows an interesting weak ferromagnetism (~0.2 MUB/Co) below 17 K arising from
      Dzyaloshinskii-Moriya interactions in Co(2+) zigzag chains, while (II) is
      essentially a paramagnet despite the presence of Cu2O6 dimers. Finally in the
      novel [Bi6O6](CoO2)(SO4)2 (III), the Co(2+) ions are ordered with sulfate in the
      interleaves, leading to a noncentrosymmetric crystal structure. 

PMID- 24940994
TI  - Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of
      liver FXR and LXRalpha.
AB  - OBJECTIVES: Increased fructose consumption causes dyslipidemia and fatty liver in
      postmenopausal women, both independent risk factors for cardiovascular disease.
      This study explored the potential mechanisms by which amla (Emblica officinalis)
      reduced hypercholesterolemia and hypertriglyceridemia and prevented fatty liver
      in a fructose-fed, ovariectomized rat model of menopause. METHODS: Sham-operated
      and ovariectomized rats were put on a chow or high fructose diet. They were
      further divided into groups with or without amla. After 18 weeks of treatment,
      livers were harvested and subjected to Western blot and histological analyses.
      RESULTS: In all groups, amla increased the protein expression of liver farnesoid
      X receptor (FXR) and liver X receptor (LXR), key proteins involved in lipid
      metabolism. Fructose-fed rats developed fatty liver and amla prevented this. Here
      amla produced an exceptional rise in LXR and insulin-induced gene-2 (Insig-2)
      which prevented the maturation of sterol regulatory element-binding protein-1 and
      steroyl CoA desaturase-1, responsible for triglyceride synthesis. Amla also
      increased the protein expression of ATP binding cassette transporter A1 (ABCA1),
      involved in high density lipoprotein (HDL) synthesis as well as low density
      lipoprotein receptor (LDLR) responsible for uptake of LDL cholesterol. Besides
      this, amla increased the protein expression of peroxisome proliferator activated
      receptor alpha (PPARalpha) involved in beta oxidation of fatty acids.
      CONCLUSIONS: Amla increased the protein expression of liver FXR, LXRalpha,
      PPARalpha and their downstream proteins Insig-2, ABCA1 and LDLR. This property of
      amla to modulate some of the key proteins involved in lipid metabolism promises
      its usefulness as a preventive agent for dyslipidemia and hepatic steatosis.

PMID- 24940993
TI  - Heterogeneous photodynamics of the pfr state in the cyanobacterial phytochrome
      Cph1.
AB  - Femtosecond photodynamics of the Pfr form of the red/far-red phytochrome N
      terminal PAS-GAF-PHY photosensory core module of the cyanobacterial phytochrome
      Cph1 (termed Cph1Delta) from Synechocystis were resolved with visible broadband
      transient absorption spectroscopy. Multiphasic generation dynamics via global
      target analysis revealed parallel evolution of two pathways with distinct excited
      and ground-state kinetics. These measurements resolved two subpopulations: a
      majority subpopulation with fast excited-state decay and slower ground-state
      dynamics, corresponding to previous descriptions of Pfr dynamics, and a minority
      subpopulation with slower excited-state decay and faster ground-state primary
      dynamics. Both excited-state subpopulations generated the isomerized, red-shifted
      Lumi-Ff photoproduct (715 nm); subsequent ground-state evolution to a blue
      shifted Meta-Fr population (635 nm) proceeded on 3 ps and 1.5 ns time scales for
      the two subpopulations. Meta-Fr was spectrally similar to a recently described
      photoinactive fluorescent subpopulation of Pr ((Fluor)Pr). Thus, the reverse Pfr
      to Pr photoconversion of Cph1Delta involves minor structural deformation of Meta
      Fr to generate the fluorescent, photochemically refractory form of Pr, with
      slower subsequent equilibration with the photoactive Pr subpopulation
      ((Photo)Pr). 

PMID- 24940996
TI  - Efficient synthesis of an indoloquinolizinium alkaloid selective DNA-binder by
      ring-closing metathesis.
AB  - Two total syntheses of the indolo[2,3-a]quinolizinium cation have been
      accomplished through the application of two ring-closing metathesis reactions to
      form the pyridinium ring. One of these approaches provides the tetracyclic cation
      in only five steps from commercially available harmane. Fluorescence-based
      thermal denaturation experiments, as well as spectrofluorimetric titration,
      circular dichroism measurements, and theoretical simulations, showed a consistent
      DNA-binding capacity by intercalation with a marked preference for AT-rich
      sequences. 

PMID- 24940997
TI  - Effects of cationic antimicrobial peptides on liquid-preserved boar spermatozoa.
AB  - Antibiotics are mandatory additives in semen extenders to control bacterial
      contamination. The worldwide increase in resistance to conventional antibiotics
      requires the search for alternatives not only for animal artificial insemination
      industries, but also for veterinary and human medicine. Cationic antimicrobial
      peptides are of interest as a novel class of antimicrobial additives for boar
      semen preservation. The present study investigated effects of two synthetic
      cyclic hexapeptides (c-WFW, c-WWW) and a synthetic helical magainin II amide
      derivative (MK5E) on boar sperm during semen storage at 16  degrees C for 4 days.
      The standard extender, Beltsville Thawing Solution (BTS) containing 250 ug/mL
      gentamicin (standard), was compared to combinations of BTS with each of the
      peptides in a split-sample procedure. Examination revealed peptide- and
      concentration-dependent effects on sperm integrity and motility. Negative effects
      were more pronounced for MK5E than in hexapeptide-supplemented samples. The
      cyclic hexapeptides were partly able to stimulate a linear progressive sperm
      movement. When using low concentrations of cyclic hexapeptides (4 uM c-WFW, 2 uM
      c-WWW) sperm quality was comparable to the standard extender over the course of
      preservation. C-WFW-supplemented boar semen resulted in normal fertility rates
      after AI. In order to investigate the interaction of peptides with the membrane,
      electron spin resonance spectroscopic measurements were performed using spin
      labeled lipids. C-WWW and c-WFW reversibly immobilized an analog of
      phosphatidylcholine (PC), whereas MK5E caused an irreversible increase of PC
      mobility. These results suggest testing the antimicrobial efficiency of non-toxic
      concentrations of selected cyclic hexapeptides as potential candidates to
      supplement/replace common antibiotics in semen preservation.

PMID- 24940999
TI  - Co-infection of blacklegged ticks with Babesia microti and Borrelia burgdorferi
      is higher than expected and acquired from small mammal hosts.
AB  - Humans in the northeastern and midwestern United States are at increasing risk of
      acquiring tickborne diseases--not only Lyme disease, but also two emerging
      diseases, human granulocytic anaplasmosis and human babesiosis. Co-infection with
      two or more of these pathogens can increase the severity of health impacts. The
      risk of co-infection is intensified by the ecology of these three diseases
      because all three pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, and
      Babesia microti) are transmitted by the same vector, blacklegged ticks (Ixodes
      scapularis), and are carried by many of the same reservoir hosts. The risk of
      exposure to multiple pathogens from a single tick bite and the sources of co
      infected ticks are not well understood. In this study, we quantify the risk of co
      infection by measuring infection prevalence in 4,368 questing nymphs throughout
      an endemic region for all three diseases (Dutchess County, NY) to determine if co
      infections occur at frequencies other than predicted by independent assortment of
      pathogens. Further, we identify sources of co-infection by quantifying rates of
      co-infection on 3,275 larval ticks fed on known hosts. We find significant
      deviations of levels of co-infection in questing nymphs, most notably 83% more co
      infection with Babesia microti and Borrelia burgdorferi than predicted by chance
      alone. Further, this pattern of increased co-infection was observed in larval
      ticks that fed on small mammal hosts, but not on meso-mammal, sciurid, or avian
      hosts. Co-infections involving A. phagocytophilum were less common, and fewer co
      infections of A. phagocytophilum and B. microti than predicted by chance were
      observed in both questing nymphs and larvae fed on small mammals. Medical
      practitioners should be aware of the elevated risk of B. microti/B. burgdorferi
      co-infection.

PMID- 24941000
TI  - A boswellic acid-containing extract ameliorates schistosomiasis liver granuloma
      and fibrosis through regulating NF-kappaB signaling in mice.
AB  - Boswellic acid (BA)-containing extracts such as BSE have anti-inflammatory and
      immunomodulatory activity. In chronic schistosomiasis, the hepatic granuloma and
      fibrosis induced by egg deposition in the liver is the most serious pathological
      manifestations. However, little is known regarding the role of BAs in Schistosoma
      japonicum (S. japonicum) egg-induced liver granuloma and fibrosis. In order to
      investigate the effect of a water-soluble complex preparation of BSE, BSE-CD, on
      S. japonicum egg-induced liver pathology, liver granuloma and fibrosis were
      induced by infecting C57BL/6 mice with 18-22 cercariae of S. japonicum. S.
      japonicum cercariae infected mice were injected with BSE-CD at the onset of egg
      granuloma formation (early phase BSE-CD treatment after 4 weeks infection) or
      after the formation of liver fibrosis (late phase BSE-CD treatment after 7 weeks
      infection). Our data show that treatment of infected mice with BSE-CD
      significantly reduced both the extent of hepatic granuloma and fibrosis.
      Consistent with an inhibition of NF-kappaB signaling as evidenced by reduced
      IkappaB kinase (IKK) activation, the mRNA expression of VEGF (vascular
      endothelial growth factor, VEGF), TNF-alpha (tumor necrosis factor-alpha TNF
      alpha) and MCP-1 (monocyte chemotactic protein 1, MCP-1) was decreased. Moreover,
      immunohistochemical analysis (IHC) revealed that the content of alpha-SMA in
      liver tissue of BSE-CD treated mice was dramatically decreased. Our findings
      suggest that BSE-CD treatment attenuates S. japonicum egg-induced hepatic
      granulomas and fibrosis, at least partly due to reduced NF-kappaB signaling and
      the subsequently decreased expression of VEGF, TNF-alpha, and MCP-1. Suppression
      of the activation of hepatic stellate cells (HSC) may also be involved in the
      therapeutic efficacy of BSE-CD. 

PMID- 24941001
TI  - Molecular hydrogen attenuates neuropathic pain in mice.
AB  - Neuropathic pain remains intractable and the development of new therapeutic
      strategies are urgently required. Accumulating evidence indicates that
      overproduction of oxidative stress is a key event in the pathogenesis of
      neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of
      antioxidants are unsuitable for continuous use in therapy. Here we show a novel
      therapeutic method against neuropathic pain: drinking water containing molecular
      hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was
      investigated using a partial sciatic nerve ligation model in mice. As indicators
      of neuropathic pain, temporal aspects of mechanical allodynia and thermal
      hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and
      thermal hyperalgesia were measured using the von Frey test and the plantar test,
      respectively. When mice were allowed to drink water containing hydrogen at a
      saturated level ad libitum after ligation, both allodynia and hyperalgesia were
      alleviated. These symptoms were also alleviated when hydrogen was administered
      only for the induction phase (from day 0 to 4 after ligation). When hydrogen was
      administered only for the maintenance phase (from day 4 to 21 after ligation),
      hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for
      the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine,
      showed that hydrogen administration suppressed oxidative stress induced by
      ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral
      administration of hydrogen water may be useful for alleviating neuropathic pain
      in a clinical setting. 

PMID- 24941003
TI  - Craniomandibular trauma and tooth loss in northern dogs and wolves: implications
      for the archaeological study of dog husbandry and domestication.
AB  - Archaeological dog remains from many areas clearly show that these animals
      suffered tooth fractures, tooth loss, trauma, and dental defects during their
      lives. Relatively little research has explored the meanings of these patterns,
      particularly for ancient dog remains from small-scale societies of the North. One
      limiting issue is the lack of comparative data on dental health and experiences
      of trauma among northern wolves and dogs. This paper examines tooth loss, tooth
      fracture, enamel hypoplasia, and cranial trauma in a large sample of historic dog
      and wolf remains from North America and Northern Russia. The data indicate that
      the dogs more commonly experienced tooth loss and tooth fracture than the wolves,
      despite reportedly being fed mostly soft foods such as blubber and fish. The
      higher rates observed in the dogs likely is a result of food stress and self
      provisioning through scavenging. The ability to self-provision was likely
      important for the long-term history of dog use in the north. Dogs also more
      commonly experienced cranial fractures than wolves, particularly depression
      fractures on their frontal bones, which were likely the result of blows from
      humans. Hypoplastic lesions are rare in both wolves and dogs, and probably result
      from multiple causes, including food stress, disease, and trauma. 

PMID- 24941002
TI  - Representing kidney development using the gene ontology.
AB  - Gene Ontology (GO) provides dynamic controlled vocabularies to aid in the
      description of the functional biological attributes and subcellular locations of
      gene products from all taxonomic groups (www.geneontology.org). Here we describe
      collaboration between the renal biomedical research community and the GO
      Consortium to improve the quality and quantity of GO terms describing renal
      development. In the associated annotation activity, the new and revised terms
      were associated with gene products involved in renal development and function.
      This project resulted in a total of 522 GO terms being added to the ontology and
      the creation of approximately 9,600 kidney-related GO term associations to 940
      UniProt Knowledgebase (UniProtKB) entries, covering 66 taxonomic groups. We
      demonstrate the impact of these improvements on the interpretation of GO term
      analyses performed on genes differentially expressed in kidney glomeruli affected
      by diabetic nephropathy. In summary, we have produced a resource that can be
      utilized in the interpretation of data from small- and large-scale experiments
      investigating molecular mechanisms of kidney function and development and thereby
      help towards alleviating renal disease. 

PMID- 24941004
TI  - Effect of P2X7 receptor knockout on AQP-5 expression of type I alveolar
      epithelial cells.
AB  - P2X7 receptors, ATP-gated cation channels, are specifically expressed in alveolar
      epithelial cells. The pathophysiological function of this lung cell type, except
      a recently reported putative involvement in surfactant secretion, is unknown. In
      addition, P2X7 receptor-deficient mice show reduced inflammation and lung
      fibrosis after exposure with bleomycin. To elucidate the role of the P2X7
      receptor in alveolar epithelial type I cells we characterized the pulmonary
      phenotype of P2X7 receptor knockout mice by using immunohistochemistry, western
      blot analysis and real-time RT PCR. No pathomorphological signs of fibrosis were
      found. Results revealed, however, a remarkable loss of aquaporin-5 protein and
      mRNA in young knockout animals. Additional in vitro experiments with bleomycin
      treated precision cut lung slices showed a greater sensitivity of the P2X7
      receptor knockout mice in terms of aquaporin-5 reduction as wild type animals.
      Finally, P2X7 receptor function was examined by using the alveolar epithelial
      cell lines E10 and MLE-12 for stimulation experiments with bleomycin. The in
      vitro activation of P2X7 receptor was connected with an increase of aquaporin-5,
      whereas the inhibition of the receptor with oxidized ATP resulted in down
      regulation of aquaporin-5. The early loss of aquaporin-5 which can be found in
      different pulmonary fibrosis models does not implicate a specific pathogenetic
      role during fibrogenesis. 

PMID- 24941005
TI  - Comparative analysis of the base compositions of the pre-mRNA 3' cleaved-off
      region and the mRNA 3' untranslated region relative to the genomic base
      composition in animals and plants.
AB  - The precursor messenger RNA (pre-mRNA) three-prime cleaved-off region (3'COR) and
      the mRNA three-prime untranslated region (3'UTR) play critical roles in
      regulating gene expression. The differences in base composition between these
      regions and the corresponding genomes are still largely uncharacterized in
      animals and plants. In this study, the base compositions of non-redundant 3'CORs
      and 3'UTRs were compared with the corresponding whole genomes of eleven animals,
      four dicotyledonous plants, and three monocotyledonous (cereal) plants. Among the
      four bases (A, C, G, and U for adenine, cytosine, guanine, and uracil,
      respectively), U (which corresponds to T, for thymine, in DNA) was the most
      frequent, A the second most frequent, G the third most frequent, and C the least
      frequent in most of the species in both the 3'COR and 3'UTR regions. In
      comparison with the whole genomes, in both regions the U content was usually the
      most overrepresented (particularly in the monocotyledonous plants), and the C
      content was the most underrepresented. The order obtained for the species groups,
      when ranked from high to low according to the U contents in the 3'COR and 3'UTR
      was as follows: dicotyledonous plants, monocotyledonous plants, non-mammal
      animals, and mammals. In contrast, the genomic T content was highest in
      dicotyledonous plants, lowest in monocotyledonous plants, and intermediate in
      animals. These results suggest the following: 1) there is a mechanism operating
      in both animals and plants which is biased toward U and against C in the 3'COR
      and 3'UTR; 2) the 3'UTR and 3'COR, as functional units, minimized the difference
      between dicotyledonous and monocotyledonous plants, while the dicotyledonous and
      monocotyledonous genomes evolved into two extreme groups in terms of base
      composition. 

PMID- 24941007
TI  - Assessing the health of the U.S. west coast with a regional-scale application of
      the Ocean Health Index.
AB  - Management of marine ecosystems increasingly demands comprehensive and
      quantitative assessments of ocean health, but lacks a tool to do so. We applied
      the recently developed Ocean Health Index to assess ocean health in the
      relatively data-rich US west coast region. The overall region scored 71 out of
      100, with sub-regions scoring from 65 (Washington) to 74 (Oregon). Highest
      scoring goals included tourism and recreation (99) and clean waters (87), while
      the lowest scoring goals were sense of place (48) and artisanal fishing
      opportunities (57). Surprisingly, even in this well-studied area data limitations
      precluded robust assessments of past trends in overall ocean health. Nonetheless,
      retrospective calculation of current status showed that many goals have declined,
      by up to 20%. In contrast, near-term future scores were on average 6% greater
      than current status across all goals and sub-regions. Application of hypothetical
      but realistic management scenarios illustrate how the Index can be used to
      predict and understand the tradeoffs among goals and consequences for overall
      ocean health. We illustrate and discuss how this index can be used to vet
      underlying assumptions and decisions with local stakeholders and decision-makers
      so that scores reflect regional knowledge, priorities and values. We also
      highlight the importance of ongoing and future monitoring that will provide
      robust data relevant to ocean health assessment. 

PMID- 24941006
TI  - Comparative proteome analysis of cryopreserved flagella and head plasma membrane
      proteins from sea bream spermatozoa: effect of antifreeze proteins.
AB  - Cryopreservation induces injuries to fish spermatozoa that in turn affect sperm
      quality in terms of fertilization ability, motility, DNA and protein integrity
      and larval survival. To reduce the loss of sperm quality due to freezing-thawing,
      it is necessary to improve these procedures. In the present study we investigated
      the ability of two antifreeze proteins (AFPI and AFPIII) to reduce the loss of
      quality of sea bream spermatozoa due to cryopreservation. To do so, we compared
      viability, motility, straight-line velocity and curvilinear velocity of fresh and
      (AFPs)-cryopreserved spermatozoa. AFPIII addition to cryopreservation medium
      improved viability, motility and straight-line velocity with respect to DMSO or
      DMSO plus AFPI. To clarify the molecular mechanism(s) underlying these findings,
      the protein profile of two different cryopreserved sperm domains, flagella and
      head plasma membranes, was analysed. The protein profiles differed between fresh
      and frozen-thawed semen and results of the image analysis demonstrated that,
      after cryopreservation, out of 270 proteins 12 were decreased and 7 were
      increased in isolated flagella, and out of 150 proteins 6 showed a significant
      decrease and 4 showed a significant increase in head membranes. Mass spectrometry
      analysis identified 6 proteins (4 from isolated flagella and 2 present both in
      flagella and head plasma membranes) within the protein spots affected by the
      freezing-thawing procedure. 3 out of 4 proteins from isolated flagella were
      involved in the sperm bioenergetic system. Our results indicate that the ability
      of AFPIII to protect sea bream sperm quality can be, at least in part, ascribed
      to reducing changes in the sperm protein profile occurring during the freezing
      thawing procedure. Our results clearly demonstrated that AFPIII addition to
      cryopreservation medium improved the protection against freezing respect to DMSO
      or DMSO plus AFPI. In addition we propose specific proteins of spermatozoa as
      markers related to the procedures of fish sperm cryopreservation. 

PMID- 24941011
TI  - Understanding the role of few-layer graphene nanosheets in enhancing the hydrogen
      sorption kinetics of magnesium hydride.
AB  - The catalytic effects of few-layer, highly wrinkled graphene nanosheet (GNS)
      addition on the dehydrogenation/rehydrogenation performance of MgH2 were
      investigated. It was found that MgH2-5 wt %GNSs nanocomposites prepared by ball
      milling exhibit relatively lower sorption temperature, faster sorption kinetics,
      and more stable cycling performance than that of pure-milled MgH2. The
      dehydrogenation step confirms that the Avrami exponent n increases from 1.22 to
      2.20 by the Johnson-Mehl-Avrami (JMA) formalism when the desorption temperature
      is reduced from 350  degrees C to 320  degrees C and 300  degrees C, implying
      that a change in the decomposition temperature can alter the mechanism during the
      dehydrogenation process. For rehydrogenation, the Avrami value n is close to 1;
      further study by several models coincident with n = 1 reveals that the absorption
      process of the MgH2-5 wt %GNSs sample conforms to the Mampel equation formulated
      through the random nucleation approach and that the nature of the absorption
      mechanism does not change within the temperature range studied. Furthermore,
      microstructure analysis demonstrated that the defective GNSs are distributed
      uniformly among the MgH2 particles and that the grain size of the MgH2-5 wt %GNSs
      nanocomposite is approximately 5-9 nm. The efficient metal-free catalytic
      dehydrogenation/rehydrogenation of MgH2 can be attributed to the coupling of the
      nanosize effect and defective GNSs. 

PMID- 24941009
TI  - Screen media usage, sleep time and academic performance in adolescents:
      clustering a self-organizing maps analysis.
AB  - Screen media usage, sleep time and socio-demographic features are related to
      adolescents' academic performance, but interrelations are little explored. This
      paper describes these interrelations and behavioral profiles clustered in low and
      high academic performance. A nationally representative sample of 3,095 Spanish
      adolescents, aged 12 to 18, was surveyed on 15 variables linked to the purpose of
      the study. A Self-Organizing Maps analysis established non-linear
      interrelationships among these variables and identified behavior patterns in
      subsequent cluster analyses. Topological interrelationships established from the
      15 emerging maps indicated that boys used more passive videogames and computers
      for playing than girls, who tended to use mobile phones to communicate with
      others. Adolescents with the highest academic performance were the youngest. They
      slept more and spent less time using sedentary screen media when compared to
      those with the lowest performance, and they also showed topological relationships
      with higher socioeconomic status adolescents. Cluster 1 grouped boys who spent
      more than 5.5 hours daily using sedentary screen media. Their academic
      performance was low and they slept an average of 8 hours daily. Cluster 2
      gathered girls with an excellent academic performance, who slept nearly 9 hours
      per day, and devoted less time daily to sedentary screen media. Academic
      performance was directly related to sleep time and socioeconomic status, but
      inversely related to overall sedentary screen media usage. Profiles from the two
      clusters were strongly differentiated by gender, age, sedentary screen media
      usage, sleep time and academic achievement. Girls with the highest academic
      results had a medium socioeconomic status in Cluster 2. Findings may contribute
      to establishing recommendations about the timing and duration of screen media
      usage in adolescents and appropriate sleep time needed to successfully meet the
      demands of school academics and to improve interventions targeting to affect
      behavioral change. 

PMID- 24941010
TI  - Intraoperative maintenance of normoglycemia with insulin and glucose preserves
      verbal learning after cardiac surgery.
AB  - OBJECTIVE: The hyperglycemic response to surgery may be a risk factor for
      cognitive dysfunction. We hypothesize that strict maintenance of normoglycemia
      during cardiac surgery preserves postoperative cognitive function. METHODS: As
      part of a larger randomized, single-blind, interventional efficacy study on the
      effects of hyperinsulinemic glucose control in cardiac surgery (NCT00524472),
      consenting patients were randomly assigned to receive combined administration of
      insulin and glucose, titrated to preserve normoglycemia (3.5-6.1 mmol L(-1);
      experimental group), or standard metabolic care (blood glucose 3.5-10 mmol L(-1);
      control group), during open heart surgery. The patients' cognitive function was
      assessed during three home visits, approximately two weeks before the operation,
      and two months and seven months after surgery. The following tests were
      performed: Rey Auditory Verbal Learning Task (RAVLT for verbal learning and
      memory), Digit Span Task (working memory), Trail Making A & B (visuomotor
      tracking and attention), and the Word Pair Task (implicit memory). Questionnaires
      measuring specific traits known to affect cognitive performance, such as self
      esteem, depression, chronic stress and social support, were also administered.
      The primary outcome was to assess the effect of hyperinsulinemic-normoglycemic
      clamp therapy versus standard therapy on specific cognitive parameters in
      patients receiving normoglycemic clamp, or standard metabolic care. RESULTS:
      Twenty-six patients completed the study with 14 patients in the normoglycemia and
      12 patients in the control group. Multiple analysis of covariance (MANCOVA) for
      the RAVLT showed a significant effect for the interaction of group by visit (F =
      4.07, p = 0.035), and group by visit by recall (F = 2.21, p = 0.04). The
      differences occurred at the second and third visit. MANCOVA for the digit span
      task, trail making and word pair association test showed no significant effect.
      CONCLUSIONS: Preserving intraoperative normoglycemia by intravenous insulin and
      glucose may prevent the impairment of memory function, both short and long-term,
      after cardiac surgery.

PMID- 24941012
TI  - Non-invasive fibrosis assessment predicts sustained virological response to
      telaprevir with pegylated interferon and ribavirin for chronic hepatitis C.
AB  - BACKGROUND: Liver fibrosis remains one of the most important predictors of
      sustained virological response (SVR) in this era of direct-acting antiviral
      treatment of chronic hepatitis C. We compare non-invasive fibrosis assessment
      with liver biopsy (METAVIR) in terms of their ability to predict SVR by
      telaprevir (TVR)-based triple therapy. METHODS: This prospective study consisted
      of 108 patients with chronic HCV genotype 1 infection who received TVR in
      combination with pegylated interferon (PEG-IFN)-alpha2b and ribavirin (RBV). Non
      invasive fibrosis data included transient elastography (FibroScan), FIB-4 index
      and aspartate aminotransferase to platelet ratio index (APRI). RESULTS: SVR was
      achieved by 84.3% of the patients by intention-to-treat analysis. In contrast to
      the high SVR rates for treatment-naive patients (87.1%, 27 of 31) and patients
      who previously relapsed (97.9%, 46 of 47), the SVR rate of prior partial/null
      responders was significantly lower (60.0%, 18 of 30). The impact of fibrosis on
      SVR was greater for prior partial/null responders, and fibrosis data, including
      both METAVIR score and non-invasive fibrosis assessments, were useful for
      predicting SVR. The METAVIR score (area under the receiver operating
      characteristic curve [AUROC] 0.91, cutoff <=F2), FibroScan values (AUROC 0.99,
      cutoff <=10.0 kPa), FIB-4 index (AUROC 0.91, cutoff <=3.5) and APRI (AUROC 0.91,
      cutoff <=0.80) were shown to have equal, excellent predictive power. CONCLUSIONS:
      An alternative to METAVIR score by liver biopsy, non-invasive fibrosis
      assessments are useful options for predicting SVR by prior partial or null
      responders in TVR-based triple therapy.

PMID- 24941018
TI  - Evaluation of Generalized Born Model Accuracy for Absolute Binding Free Energy
      Calculations.
AB  - Generalized Born (GB) implicit solvent models are widely used in molecular
      dynamics simulations to evaluate the interactions of biomolecular complexes. The
      continuum treatment of the solvent results in significant computational savings
      in comparison to an explicit solvent representation. It is, however, not clear
      how accurately the GB approach reproduces the absolute free energies of
      biomolecular binding. On the basis of induced dissociation by means of umbrella
      sampling simulations, the absolute binding free energies of small proline-rich
      peptide ligands and a protein receptor were calculated. Comparative simulations
      according to the same protocol were performed by employing an explicit solvent
      model and various GB-type implicit solvent models in combination with a nonpolar
      surface tension term. The peptide ligands differed in a key residue at the
      peptide-protein interface, including either a nonpolar, a neutral polar, a
      positively charged, or a negatively charged group. For the peptides with a
      neutral polar or nonpolar interface residue, very good agreement between the
      explicit solvent and GB implicit solvent results was found. Deviations in the
      main separation free energy contributions are smaller than 1 kcal/mol. In
      contrast, for peptides with a charged interface residue, significant deviations
      of 2-4 kcal/mol were observed. The results indicate that recent GB models can
      compete with explicit solvent representations in total binding free energy
      calculations as long as no charged residues are present at the binding interface.

PMID- 24941013
TI  - Cardiovascular effects of dietary salt intake in aged healthy cats: a 2-year
      prospective randomized, blinded, and controlled study.
AB  - High salt dry expanded diets are commercially available for cats to increase
      water intake and urine volume, as part of the prevention or treatment of
      naturally occurring urinary stone formation (calcium oxalates and struvites).
      However, chronic high salt intake may have potential cardiovascular adverse
      effects in both humans, especially in aging individuals, and several animal
      models. The objective of this prospective, randomized, blinded, and controlled
      study was to assess the long-term cardiovascular effects of high salt intake in
      healthy aged cats. Twenty healthy neutered cats (10.1 +/- 2.4 years) were
      randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1
      g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same
      composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride).
      Clinical examination, systolic and diastolic arterial blood pressure
      measurements, standard transthoracic echocardiography and conventional Doppler
      examinations were repeatedly performed on non-sedated cats by trained observers
      before and over 24 months after diet implementation. Radial and longitudinal
      velocities of the left ventricular free wall and the interventricular septum were
      also assessed in systole and diastole using 2-dimensional color tissue Doppler
      imaging. Statistics were performed using a general linear model. No significant
      effect of dietary salt intake was observed on systolic and diastolic arterial
      blood pressure values. Out of the 33 tested imaging variables, the only one
      affected by dietary salt intake was the radial early on late diastolic velocity
      ratio assessed in the endocardium of the left ventricular free wall,
      statistically lower in the high salt diet group at 12 months only (P = 0.044). In
      conclusion, in this study involving healthy aged cats, chronic high dietary salt
      intake was not associated with an increased risk of systemic arterial
      hypertension and myocardial dysfunction, as observed in some elderly people, salt
      sensitive patients and animal models.

PMID- 24941017
TI  - Evapotranspiration measurement and crop coefficient estimation over a spring
      wheat Farmland ecosystem in the Loess Plateau.
AB  - Evapotranspiration (ET) is an important component of the surface energy balance
      and hydrological cycle. In this study, the eddy covariance technique was used to
      measure ET of the semi-arid farmland ecosystem in the Loess Plateau during 2010
      growing season (April to September). The characteristics and environmental
      regulations of ET and crop coefficient (Kc) were investigated. The results showed
      that the diurnal variation of latent heat flux (LE) was similar to single-peak
      shape for each month, with the largest peak value of LE occurring in August
      (151.4 W m(-2)). The daily ET rate of the semi-arid farmland in the Loess Plateau
      also showed clear seasonal variation, with the maximum daily ET rate of 4.69 mm
      day(-1). Cumulative ET during 2010 growing season was 252.4 mm, and lower than
      precipitation. Radiation was the main driver of farmland ET in the Loess Plateau,
      which explained 88% of the variances in daily ET (p<0.001). The farmland Kc
      values showed the obvious seasonal fluctuation, with the average of 0.46. The
      correlation analysis between daily Kc and its major environmental factors
      indicated that wind speed (Ws), relative humidity (RH), soil water content (SWC),
      and atmospheric vapor pressure deficit (VPD) were the major environmental
      regulations of daily Kc. The regression analysis results showed that Kc
      exponentially decreased with Ws increase, an exponentially increased with RH, SWC
      increase, and a linearly decreased with VPD increase. An experiential Kc model
      for the semi-arid farmland in the Loess Plateau, driven by Ws, RH, SWC and VPD,
      was developed, showing a good consistency between the simulated and the measured
      Kc values.

PMID- 24941019
TI  - Impacts of variability in cellulosic biomass yields on energy security.
AB  - The practice of modeling biomass yields on the basis of deterministic point
      values aggregated over space and time obscures important risks associated with
      large-scale biofuel use, particularly risks related to drought-induced yield
      reductions that may become increasingly frequent under a changing climate. Using
      switchgrass as a case study, this work quantifies the variability in expected
      yields over time and space through switchgrass growth modeling under historical
      and simulated future weather. The predicted switchgrass yields across the United
      States range from about 12 to 19 Mg/ha, and the 80% confidence intervals range
      from 20 to 60% of the mean. Average yields are predicted to decrease with
      increased temperatures and weather variability induced by climate change.
      Feedstock yield variability needs to be a central part of modeling to ensure that
      policy makers acknowledge risks to energy supplies and develop strategies or
      contingency plans that mitigate those risks. 

PMID- 24941022
TI  - Case study on temperature-accelerated molecular dynamics simulation of ligand
      dissociation: inducer dissociation from the Lac repressor protein.
AB  - We studied ligand dissociation from the inducer-binding domain of the Lac
      repressor protein using temperature-accelerated molecular dynamics (TAMD)
      simulations. With TAMD, ligand dissociation could be observed within relatively
      short simulation time. This allowed many dissociation trajectories to be sampled.
      Under the adiabatic approximation of TAMD, all but one degree of freedom of the
      system were sampled from usual canonical ensembles at room temperature. Thus,
      meaningful statistical analyses could be carried out on the trajectories. A
      systematic approach was proposed to analyze possible correlations between ligand
      dissociation and fluctuations of various protein conformational coordinates.
      These analyses employed relative entropies, allowing both linear and nonlinear
      correlations to be considered. Applying the simulation and analysis methods to
      the inducer binding domain of the Lac repressor protein, we found that ligand
      dissociation from this protein correlated mainly with fluctuations of side-chain
      conformations of a few residues that surround the binding pocket. In addition,
      the two binding sites of the dimeric protein were dynamically coupled: occupation
      of one site by an inducer molecule could significantly reduce or slow down
      conformational dynamics around the other binding pocket. 

PMID- 24941021
TI  - Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition
      to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair
      deficiency.
AB  - Little is known about the genetic factors that contribute to familial colorectal
      cancer type X (FCCX), characterized by hereditary nonpolyposis colorectal
      carcinoma with no mismatch repair defects. Genetic linkage analysis, exome
      sequencing, tumor studies, and functional investigations of 4 generations of a
      FCCX family led to the identification of a truncating germline mutation in RPS20,
      which encodes a component (S20) of the small ribosomal subunit and is a new colon
      cancer predisposition gene. The mutation was associated with a defect in pre
      ribosomal RNA maturation. Our findings show that mutations in a gene encoding a
      ribosomal protein can predispose individuals to microsatellite-stable colon
      cancer. Evaluation of additional FCCX families for mutations in RPS20 and other
      ribosome-associated genes is warranted. 

PMID- 24941023
TI  - Complex conformational heterogeneity of the highly flexible O6-benzyl-guanine DNA
      adduct.
AB  - The conformational preference of the O6-benzyl-guanine (BzG) adduct was
      computationally examined using nucleoside, nucleotide, and DNA models, which
      provided critical information about the potential mutagenic consequences and
      toxicity of the BzG adduct in our cells. Substantial conformational flexibility
      of the BzG moiety, including rotation of the bulky group with respect to the base
      and the internal conformation of the bulk moiety, is seen in the nucleoside and
      nucleotide models. This large conformational flexibility suggests the
      conformation adopted by BzG is dependent on the local environment of the BzG
      adduct. Upon incorporation of the adduct into the DNA helix, the BzG
      conformational flexibility is maintained. The range of BzG conformations adopted
      in DNA likely arises due to a combination of the long and flexible (-CH2-)
      linker, the small adduct size, and the lack of discrete interactions between the
      bulky moiety and G. Because of the conformational flexibility of the adduct, many
      DNA conformations are observed for BzG adducted DNA, including those not
      previously reported in the literature, and thus, a modified nomenclature for
      adducted DNA conformations is presented. Furthermore, the preferred conformation
      of BzG adducted DNA is greatly dependent on a number of factors, including the
      pairing nucleotide, the discrete interactions in the helix, and the solvation of
      the benzyl moiety. These factors in turn lead to a complicated mutagenic and
      toxic profile that may invoke pairing with natural C, mispairs, or deletion
      mutations, which is supported by previously reported experimental biochemical
      studies. Despite this complex mutagenic profile, pairing with C leads to the most
      stable helical structure, which is the first combined structural and energetic
      explanation for experimental studies reporting a higher rate of C incorporation
      than any other nucleobase upon BzG replication. 

PMID- 24941020
TI  - Fumagillin prodrug nanotherapy suppresses macrophage inflammatory response via
      endothelial nitric oxide.
AB  - Antiangiogenesis has been extensively explored for the treatment of a variety of
      cancers and certain inflammatory processes. Fumagillin, a mycotoxin produced by
      Aspergillus fumigatus that binds methionine aminopeptidase 2 (MetAP-2), is a
      potent antiangiogenic agent. Native fumagillin, however, is poorly soluble and
      extremely unstable. We have developed a lipase-labile fumagillin prodrug (Fum-PD)
      that eliminated the photoinstability of the compound. Using alphavbeta3-integrin
      targeted perfluorocarbon nanocarriers to deliver Fum-PD specifically to
      angiogenic vessels, we effectively suppressed clinical disease in an experimental
      model of rheumatoid arthritis (RA). The exact mechanism by which Fum-PD-loaded
      targeted nanoparticles suppressed inflammation in experimental RA, however,
      remained unexplained. We herein present evidence that Fum-PD nanotherapy
      indirectly suppresses inflammation in experimental RA through the local
      production of endothelial nitric oxide (NO). Fum-PD-induced NO activates AMP
      activated protein kinase (AMPK), which subsequently modulates macrophage
      inflammatory response. In vivo, NO-induced AMPK activation inhibits mammalian
      target of rapamycin (mTOR) activity and enhances autophagic flux, as evidenced by
      p62 depletion and increased autolysosome formation. Autophagy in turn mediates
      the degradation of IkappaB kinase (IKK), suppressing the NF-kappaB p65 signaling
      pathway and inflammatory cytokine release. Inhibition of NO production by N(G)
      nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor,
      reverses the suppression of NF-kappaB-mediated inflammatory response induced by
      Fum-PD nanotherapy. These unexpected results uncover an activity of Fum-PD
      nanotherapy that may be further explored in the treatment of angiogenesis
      dependent diseases.

PMID- 24941024
TI  - Searching for the definition of macrosomia through an outcome-based approach.
AB  - BACKGROUND: Macrosomia has been defined in various ways by obstetricians and
      researchers. The purpose of the present study was to search for a definition of
      macrosomia through an outcome-based approach. METHODS: In a study of 30,831,694
      singleton term live births and 38,053 stillbirths in the U.S. Linked Birth-Infant
      Death Cohort datasets (1995-2004), we compared the occurrence of stillbirth,
      neonatal death, and 5-min Apgar score less than four in subgroups of birthweight
      (4000-4099 g, 4100-4199 g, 4200-4299 g, 4300-4399 g, 4400-4499 g, 4500-4999 g vs.
      reference group 3500-4000 g) and birthweight percentile for gestational age (90th
      94th percentile, 95th-96th, and >= 97th percentile, vs. reference group 75th-90th
      percentile). RESULTS: There was no significant increase in adverse perinatal
      outcomes until birthweight exceeded the 97th percentile. Weight-specific odds
      ratios (ORs) elevated substantially to 2 when birthweight exceeded 4500 g in
      Whites. In Blacks and Hispanics, the aORs exceeded 2 for 5-min Apgar less than
      four when birthweight exceeded 4300 g. For vaginal deliveries, the aORs of
      perinatal morbidity and mortality were larger for most of the subgroups, but the
      patterns remained the same. CONCLUSIONS: A birthweight greater than 4500 g in
      Whites, or 4300 g in Blacks and Hispanics regardless of gestational age is the
      optimal threshold to define macrosomia. A birthweight greater than the 97th
      percentile for a given gestational age, irrespective of race is also reasonable
      to define macrosomia. The former may be more clinically useful and simpler to
      apply.

PMID- 24941026
TI  - The influence of acculturation on substance use behaviors among Latina sexual
      minority women: the mediating role of discrimination.
AB  - BACKGROUND: A large body of work has demonstrated that sexual minority women have
      elevated rates of substance use morbidity, as compared with heterosexual women,
      and that this might be especially true for women of color. OBJECTIVES: This study
      examines the influence of acculturation and discrimination on substance use among
      Latina sexual minority women. METHODS: Data were collected from 2007 to 2008 as
      part of a larger community-based survey in the greater Chicago area. Scales
      measured discrimination, acculturation, and substance use. Structural equation
      modeling validated scales and examined their relationships, which were further
      described via mediation analysis. RESULTS: Increased acculturation leads to
      substance use and this relationship is partially mediated by discrimination
      (Sobel test = 2.10; p < .05). CONCLUSIONS/IMPORTANCE: Implications of these
      findings and directions for future research are discussed. Funding was provided
      by several women's and public health organizations.

PMID- 24941027
TI  - Severe haze episodes and seriously polluted fog water in Ji'nan, China.
AB  - Haze episodes often hit urban cities in China recently. Here, we present several
      continuous haze episodes with extremely high PM2.5 levels that occurred over
      several weeks in early 2013 and extended across most parts of the northern and
      eastern China-far exceeding the Beijing-Tianjin-Hebei region. Particularly, the
      haze episode covered ~1 million km(2) on January 14, 2013 and the daily averaged
      PM2.5 concentration exceeded 360 MUg m(-3) in Ji'nan. The observed maximum hourly
      PM2.5 concentration in urban Ji'nan reached 701 MUg m(-3) at 7:00 am (local time)
      in January 30. During these haze episodes, several fog events happened and the
      concurrent fog water was found to be seriously polluted. For the fog water
      collected in Ji'nan from 10:00 pm in January 14 to 11:00 am in January 15,
      sulfate, nitrate, and ammonium were the major ions with concentrations of 1.54 *
      10(6), 8.98 * 10(5), and 1.75 * 10(6) MUeq L(-1), respectively, leading to a low
      in-situ pH of 3.30. The sulfate content in the fog sample was more than 544 times
      as high as those observed in other areas. With examination of the simultaneously
      observed data on PM2.5 and its chemical composition, the fog played a role in
      scavenging and removing fine particles from the atmosphere during haze episodes
      and thus was seriously contaminated. However, the effect was not sufficient to
      obviously cleanse air pollution and block haze episodes.

PMID- 24941028
TI  - Dysplasia epiphysealis hemimelica - diagnostics and treatment in pediatric
      patients.
AB  - BACKGROUND: Dysplasia epiphysealis hemimelica, also known as Trevor-Fairbanks
      disease, is a rare developmental disorder The objective of this article is to
      present own observations and experience in treating patients with dysplasia
      epiphysealis hemimelica. MATERIAL AND METHODS: Six children with dysplasia
      epiphysealis hemimelica were treated in years 1990-2007. The mean age of
      observation was 8.5 years (from 3 to 19 years). Analysis of medical and
      radiological documentation of patients was performed to collect data on symptoms,
      disease location, management and outcomes. RESULTS: The main symptoms reported by
      patients included limited range of motion of the affected joints with pain (66%)
      and deformed joint outline (34%). Four patients were subjected to surgical
      treatment while conservative treatment was applied in the other two. Lated
      complications were observed in two patients after surgical intervention (50%). In
      patients undergoing conservative treatment, one positive outcome and one negative
      outcome involving complete hip ankylosis, were observed. CONCLUSIONS: Correct
      diagnosis is very important as it may save the patient from unnecessary surgery
      and, if the surgery is necessary, it may help in performing it correctly. In
      patients presenting with joint pains, joint deformations, and tuberous lesions in
      joints possibility of dysplasia epiphysealis hemimelica should be taken into
      account. The treatment should start with conservative treatment, particularly
      physical therapy applied in the region of pain. If pain, joint deformation or
      limited range of motion of the affected joint persist, surgical treatment
      consisting of complete excision of the lesion should be taken into account.

PMID- 24941030
TI  - Systemic-pulmonary artery shunts in infants: modified Blalock-Taussig and central
      shunt procedures.
AB  - Access is gained through a midline sternotomy, the thymus partially excised and
      the superior part of the pericardium is opened. The innominate vein is retracted
      and the innominate artery is mobilized up to the bifurcation. The aorta is
      retracted to the left, the superior vena cavae to the right and the right atrial
      appendage inferiorly. The adventitia around the right pulmonary artery (PA) is
      dissected, taking care to incise the bulky pericardial reflection between the
      superior vena cavae and the trachea. Heparin is administrated. An occlusive clamp
      is applied to the right PA to test for haemodynamic tolerance prior to proceeding
      with the interposition of a suitable size artificial vascular prosthesis, based
      on the weight of the patient, between the innominate artery, or proximal
      subclavian artery and the right PA. Alternatively, if a sufficient main PA is
      present and adequate flow from a patent ductus arteriosus an end-to-side
      interposition shunt may be constructed between the ascending aorta and the main
      PA, provided the patient is stable with the test occlusion of the main PA. The
      management of the patent arterial ductus depends on whether or not there is
      forward flow through the PA. 

PMID- 24941032
TI  - Mycelial fermentation characteristics and anti-fatigue activities of a Chinese
      caterpillar fungus, Ophiocordyceps sinensis strain Cs-HK1 (Ascomycetes).
AB  - Mycelial fermentation of an Ophiocordyceps sinensis strain Cs-HK1 was carried out
      in various volumes of stirred-tank fermenters from 1.6-L and 15-L laboratory
      scale to 2000-L industrial scale. The mycelial growth in most fermenters had a
      higher rate, due probably to more efficient oxygen supply, than in shake-flasks.
      The mycelial fermentation was successfully scaled up to 2000-L industrial
      fermenters, achieving 30 g/L maximum biomass in 5 days. The Cs-HK1 mycelia formed
      hairy and fluffy pellets in the fermentation medium and the mycelial broth
      exhibited pseudoplastic rheology following the power law, with the flow behavior
      index n decreasing from 0.5 to 0.3, and the flow consistency K and the apparent
      viscosity ualpha increasing with time and biomass concentration. The mycelial
      broth containing biomass and extracellular products harvested from 2000-L
      fermenters was tested for anti-fatigue activities in forced animal swimming
      experiments. The mycelium hot water extract showed the most significant effects,
      increasing the swimming endurance of mice up to 100%, and also increasing the
      glycogen levels and reducing the lactic acid and blood urea nitrogen levels
      significantly. The results demonstrated the feasibility of Cs-HK1 mycelial
      fermentation for large-scale production of bioactive and medicinal materials. 

PMID- 24941031
TI  - Multihapten approach leading to a sensitive ELISA with broad cross-reactivity to
      microcystins and nodularin.
AB  - Microcystins (MCs) are a group of biotoxins (>150) produced by cyanobacteria,
      with a worldwide distribution. MCs are hepatotoxic, and acute exposure causes
      severe liver damage in humans and animals. Rapid and cheap methods of analysis
      are therefore required to protect people and livestock, especially in developing
      countries. To include as many MCs as possible in a single analysis, we developed
      a new competitive ELISA. Ovine polyclonal antibodies were raised using an
      immunogen made by conjugating a mixture of microcystins to cationised bovine
      serum albumin, and the plate-coating antigen was prepared by conjugating [Asp3]MC
      RY to ovalbumin. This strategy was used also to minimize specificity for
      particular microcystin congeners. Cross-reactivity studies indicate that the
      ELISA has broad specificity to microcystins and also detects nodularin, providing
      a sensitive and rapid analytical method for screening large numbers of samples.
      The limit of quantitation for microcystins in drinking water is 0.04 MUg/L, well
      below the WHO's maximum recommendation of 1 MUg/L. The ELISA can be used for
      quantifying total microcystins in various matrices, including drinking water,
      cyanobacterial cultures, extracts, and algal blooms, and may be useful in
      detecting metabolites and conjugates of MCs.

PMID- 24941029
TI  - Design of asymmetric particles containing a charged interior and a neutral
      surface charge: comparative study on in vivo circulation of polyelectrolyte
      microgels.
AB  - Lowering the modulus of hydrogel particles could enable them to bypass in vivo
      physical barriers that would otherwise filter particles with similar size but
      higher modulus. Incorporation of electrolyte moieties into the polymer network of
      hydrogel particles to increase the swelling ratio is a straightforward and quite
      efficient way to decrease the modulus. In addition, charged groups in hydrogel
      particles can also help secure cargoes. However, the distribution of charged
      groups on the surface of a particle can accelerate the clearance of particles.
      Herein, we developed a method to synthesize highly swollen microgels of precise
      size with near-neutral surface charge while retaining interior charged groups. A
      strategy was employed to enable a particle to be highly cross-linked with very
      small mesh size, and subsequently PEGylated to quench the exterior amines only
      without affecting the internal amines. Acidic degradation of the cross-linker
      allows for swelling of the particles to microgels with a desired size and
      deformability. The microgels fabricated demonstrated extended circulation in vivo
      compared to their counterparts with a charged surface, and could potentially be
      utilized in in vivo applications including as oxygen carriers or nucleic acid
      scavengers. 

PMID- 24941033
TI  - Three types of geranylgeranyl diphosphate synthases from the medicinal
      caterpillar fungus, Cordyceps militaris (Ascomycetes).
AB  - Geranylgeranyl diphosphate synthase (GGPPS) is a key enzyme in the carotenoid
      biosynthetic pathway, catalyzing the synthesis of its C20 precursor. In the
      present study, three types of ggpps genes were cloned and analyzed from the
      Caterpillar Medicinal Fungus Cordyceps militaris, a valued carotenoid-producing
      species. The sequences were named as ggpps727, ggpps191, and ggpps595. The open
      reading frame codes for predicted polypeptides of 464, 550, and 431 aa. Three
      predicted GGPPSs had a high similarity to that from Beauveria bassiana ARSEF 2860
      with identity of 73%, 71%, and 56%, respectively. Homology comparison of the
      deduced peptide sequences of the various GGPPSs revealed highly conserved
      domains. Both GGPPS727 and GGPPS191 from C. militaris contained all five domains
      highly conserved among prenyltransferases as well as two aspartate-rich DDXX(XX)D
      motifs in domains II and V, which have been proven essential for
      prenyltransferase activity. By constructing the phylogenetic tree of fungal
      GGPPSs, it was found that fungi-derived GGPPSs could be divided into three
      clusters, suggesting there were three types of GGPPSs in fungi. Each type may be
      responsible for a different metabolism. Three types of GGPPSs from C. militaris
      belonged to the different clusters separately. Expression analysis of three ggpps
      genes during the fruit body cultivation of C. militaris by real-time polymerase
      chain reaction (PCR) suggested the ggpps 191 gene may be involved in the
      synthesis of carotenoids and ggpps 727 may be responsible for primary metabolism.
      This is the first report of the GGPPS from C. militaris, a valued edible and
      medicinal fungus. 

PMID- 24941034
TI  - Process optimization for extraction of carotenoids from medicinal caterpillar
      fungus, Cordyceps militaris (Ascomycetes).
AB  - Natural carotenoids have attracted great attention for their important beneficial
      effects on human health and food coloring function. Cordyceps militaris, a well
      known edible and medicinal fungus, is a potential source of natural carotenoids.
      The present study aimed to optimize the process parameters for carotenoid
      extraction from this mushroom. The effects of different methods of breaking the
      fungal cell wall and organic solvents were studied by the one-factor-at-a-time
      method. Subsequently, the process parameters including the duration of the
      extraction time, the number of extractions, and the solvent to solid ratio were
      optimized by using the Box-Behnken design. The optimal extraction conditions
      included using an acid-heating method to break the cell wall and later extracting
      three times, each for a 1 h duration, with a 4:1 mixture of acetone: petroleum
      ether and a solvent: solid ratio of 24:1. The carotenoid content varied from
      2122.50 to 3847.50 ug/g dry weights in different commercially obtained fruit
      bodies of C. militaris. The results demonstrated that the C. militaris contained
      more carotenoid content in its fruit bodies than other known mushrooms. Stability
      monitoring by HPLC demonstrated that the carotenoids could be stored at 4 degrees
      C for 40 d. It is suggested that the carotenoid content should be considered as
      the quality standard of commercial products of this valued mushroom. These
      findings will facilitate the exploration of carotenoids from C. militaris. 

PMID- 24941035
TI  - Enhancement of antioxidant properties and increase of content of vitamin D2 and
      non-volatile components in fresh button mushroom, Agaricus bisporus (higher
      Basidiomycetes) by gamma-irradiation.
AB  - Agaricus bisporus is a popular culinary-medicinal mushroom in Taiwan, and gamma
      irradiation could extend its shelf life. Our objective was to study the content
      of vitamin D2 and the taste components and antioxidant properties of ethanolic
      extracts from A. bisporus with various doses of gamma-irradiation. After
      irradiation, the vitamin D2 content of 5-10 kGy irradiated mushrooms was in the
      range of 5.22-7.90 ug/g, higher than that of the unirradiated control (2.24
      ug/g). For all treatments, the total content of soluble sugars and polyols ranged
      from 113 to 142 mg/g, and the monosodium glutamate-like components ranged from
      6.57 to 13.50 mg/g, among which the 2.5 kGy irradiated sample has the highest
      content of flavor 5'-nucleotide. About antioxidant properties, 10 kGy irradiated
      samples exhibited lower EC50 values than did other samples. EC50 values were less
      than 5 mg/mL for ethanolic extracts. Total phenols were the major antioxidant
      components and the total content was 13.24-22.78 mg gallic acid equivalents/g.
      Based on the results obtained, gamma-irradiation could be used to improve the
      vitamin D2 content and intensity of umami taste in fresh mushrooms. In addition,
      gamma-irradiation not only maintained the antioxidant properties of mushrooms but
      also enhanced the antioxidant properties to some extent. 

PMID- 24941036
TI  - Extraction and purification of polysaccharides from pine medicinal mushroom,
      Tricholoma matsutake (higher Basidiomycetes) fruit bodies.
AB  - Ultrasound-assisted extraction, purification, and characterization of antioxidant
      polysaccharides from Tricholoma matsutake were carried out. On the basis of the
      results of a single-factor test, three independent and main variables, including
      extraction time (X1: 130-170 s), ultrasonic power (X2: 340-380 W), and ratio of
      water to raw material (X3: 45-55 mL/g) were studied by Box-Behnken design. The
      optimum extraction conditions are as follows: extraction time 160 s, ultrasonic
      power 365 W, and ratio of water to raw material 53.5 mL/g. Under the optimized
      conditions, the yield of T. matsutake polysaccharides (TMP) was 7.97+/-0.31%. The
      crude TMP was purified by DEAE-cellulose 52 chromatography and Sephadex G-100
      chromatography to afford two fractions, TMP-1 and TMP-2. The crude TMP contained
      85.76% carbohydrates, 3.57% proteins, and 0.13% uronic acids. The constituent
      monosaccharides were predominantly glucose, galactose, mannose, xylose, fucose,
      and glucuronic acid residues. 

PMID- 24941037
TI  - Development of an expression plasmid and its use in genetic manipulation of
      Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes).
AB  - We report the construction of a plasmid, pJW-EXP, designed for the expression of
      homologous and heterologous genes in Ganoderma lucidum. pJW-EXP was generated
      from the plasmid pMD19-T by inserting the G. lucidum glyceraldehyde-3-phosphate
      dehydrogenase gene promoter, the G. lucidum iron-sulfur protein subunit of
      succinate dehydrogenase gene terminator and the homologous carboxin-resistance
      gene as selection marker. This expression plasmid can be efficiently transformed
      into Ganoderma through polyethylene glycol-mediated protoplast transformation.
      Southern blot analysis showed that most of the integrated DNA appeared as
      multiple copies in the genome. The applicability of the constructed plasmid was
      tested by expression of the truncated G. lucidum 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMGR) gene that encodes the catalytic domain of HMGR.
      Overexpression of the truncated HMGR gene, which is a key gene in the
      biosynthetic pathway of the antitumor compounds, ganoderic acids, increased the
      transcription of the HMGR gene and enhanced ganoderic acid accumulation. pJW-EXP
      can serve as a useful tool in the genetic improvement and metabolic engineering
      of Ganoderma. 

PMID- 24941038
TI  - Molecular characterization of shiitake medicinal mushroom, Lentinus edodes
      strains (higher Basidiomycetes) using RAPD and ITS sequencing.
AB  - The molecular phylogeny in seven strains of Lentinus edodes was studied based on
      RAPD and their internal transcribed spacers (ITS) regions. The strains were
      analyzed by RAPD with 20 arbitrary primers. Fifteen primers were found efficient
      for the amplification of the genomic DNA. The size of the polymorphic bands were
      in the range of 100-1000 bp. However, the size of ITS1-2 and ITS1-4 regions
      varied among the strains from 278 to 575 bp and from 410 to 616 bp, respectively.
      The higher alignment score of the ITS 1-2 region indicated more variability in
      the ITS 1-4 region. Thus, on the basis of RAPD-PCR and ITS sequencing it was
      found that strains LeC and LeI showed a high degree of divergence from all other
      strains. 

PMID- 24941039
TI  - Inhibitory activity of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum
      (higher Basidiomycetes) on transformed cells by human papillomavirus.
AB  - In this study, we investigated the effects of the aqueous extracts of Lingzhi or
      Reishi medicinal mushroom, Ganoderma lucidum, obtained from three localities
      (China; and Morelos and Michoacan, Mexico) on cervical cells transformed by human
      papillomavirus (HeLa and SiHa) and C-33A cancer cells. The cells were plated in
      DMEM medium supplemented, and were incubated in the presence of different
      concentrations of G. lucidum for 24 h. Cell proliferation was determined by MTT
      colorimetric assay and viability by trypan blue assay. Inhibitory dose was
      determined (IC50) of the three different extracts of G. lucidum in the culture
      cell lines mentioned above. The apoptosis process was confirmed by nuclear DNA
      fragmentation and the cell cycle was determined by flow cytometry. The results
      showed that aqueous extracts G. lucidum obtained from three localities produced
      inhibition in the proliferation of VPH transformed cells; they also induced
      apoptosis and cell cycle arrest in HeLa, SiHa, and C-33A cancer cells. Therefore,
      it was found that aqueous extracts G. lucidum obtained from three different
      locations produced inhibitory effect on cancer cells and may have a potential
      therapeutic use for the prevention and treatment of this disease. 

PMID- 24941040
TI  - Ancient Chinese people's knowledge of macrofungi as medicinal material during the
      period from 581 to 979 AD.
AB  - Ancient Chinese knowledge of macrofungi during the period from 581 to 979 ad is
      carefully examined and discussed on the basis of previous studies and a mass of
      relevant texts from the period. The knowledge of macrofungi during this period
      was broadened by critically inheriting past literature and adding new findings
      and knowledge, which could be primarily reflected by the knowledge of the
      medicinal properties of macrofungi. The exploration of the reliable ways to
      distinguish edible macrofungi from poisonous ones received special attention from
      the physicians of this period, despite the fact that none of them were totally
      reliable. Still, in the field of agriculture, an important achievement was that
      of new macrofungi cultivation techniques. The notes on macrofungi in literary
      pieces as well as Taoist works provided many vivid accounts of the uses and
      nomenclature of macrofungi in Chinese culture. 

PMID- 24941042
TI  - Deciphering the cis-regulatory elements for XYR1 and CRE1 regulators in
      Trichoderma reesei.
AB  - In this work, we report the in silico identification of the cis-regulatory
      elements for XYR1 and CRE1 proteins in the filamentous fungus Trichoderma reesei,
      two regulators that play a central role in the expression of cellulase genes.
      Using four datasets of condition-dependent genes from RNA-seq and RT-qPCR
      experiments, we performed unsupervised motif discovery and found two short motifs
      resembling the proposed binding consensus for XYR1 and CRE1. Using these motifs,
      we analysed the presence and arrangement of putative cis-regulatory elements
      recognized by both regulators and found that shortly spaced sites were more
      associated with XYR1- and CRE1-dependent promoters than single, high-score sites.
      Furthermore, the approach used here allowed the identification of the previously
      reported XYR1-binding sites from cel7a and xyn1 promoters, and we also mapped the
      potential target sequence for this regulator at the cel6a promoter that has been
      suggested but not identified previously. Additionally, seven other promoters (for
      cel7b, cel61a, cel61b, cel3c, cel3d, xyn3 and swo genes) presented a putative
      XYR1-binding site, and strong sites for CRE1 were found at the xyr1 and cel7b
      promoters. Using the cis-regulatory architectures nearly defined for XYR1 and
      CRE1, we performed genome-wide identification of potential targets for direct
      regulation by both proteins and important differences on their functional
      regulons were elucidated. Finally, we performed binding site mapping on the
      promoters of differentially expressed genes found in T. reesei mutant strains
      lacking xyr1 or cre1 and found that indirect regulation plays a key role on their
      signalling pathways. Taken together, the data provided here sheds new light on
      the mechanisms for signal integration mediated by XYR1 and CRE1 at cellulase
      promoters. 

PMID- 24941043
TI  - Mitochondrial DNA markers reveal high genetic diversity but low genetic
      differentiation in the black fly Simulium tani Takaoka & Davies along an
      elevational gradient in Malaysia.
AB  - The population genetic structure of Simulium tani was inferred from mitochondria
      encoded sequences of cytochrome c oxidase subunits I (COI) and II (COII) along an
      elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony
      network of 71 individuals revealed 71 haplotypes in the COI gene and 43
      haplotypes in the COII gene; the concatenated sequences of the COI and COII genes
      revealed 71 haplotypes. High levels of genetic diversity but low levels of
      genetic differentiation were observed among populations of S. tani at five
      elevations. The degree of genetic diversity, however, was not in accordance with
      an altitudinal gradient, and a Mantel test indicated that elevation did not have
      a limiting effect on gene flow. No ancestral haplotype of S. tani was found among
      the populations. Pupae with unique structural characters at the highest elevation
      showed a tendency to form their own haplotype cluster, as revealed by the COII
      gene. Tajima's D, Fu's Fs, and mismatch distribution tests revealed population
      expansion of S. tani in Cameron Highlands. A strong correlation was found between
      nucleotide diversity and the levels of dissolved oxygen in the streams where S.
      tani was collected. 

PMID- 24941046
TI  - Informal urban green-space: comparison of quantity and characteristics in
      Brisbane, Australia and Sapporo, Japan.
AB  - Informal urban green-space (IGS) such as vacant lots, brownfields and street or
      railway verges is receiving growing attention from urban scholars. Research has
      shown IGS can provide recreational space for residents and habitat for flora and
      fauna, yet we know little about the quantity, spatial distribution, vegetation
      structure or accessibility of IGS. We also lack a commonly accepted definition of
      IGS and a method that can be used for its rapid quantitative assessment. This
      paper advances a definition and typology of IGS that has potential for global
      application. Based on this definition, IGS land use percentage in central
      Brisbane, Australia and Sapporo, Japan was systematically surveyed in a 10*10 km
      grid containing 121 sampling sites of 2,500 m2 per city, drawing on data recorded
      in the field and aerial photography. Spatial distribution, vegetation structure
      and accessibility of IGS were also analyzed. We found approximately 6.3% of the
      surveyed urban area in Brisbane and 4.8% in Sapporo consisted of IGS, a non
      significant difference. The street verge IGS type (80.4% of all IGS) dominated in
      Brisbane, while lots (42.2%) and gaps (19.2%) were the two largest IGS types in
      Sapporo. IGS was widely distributed throughout both survey areas. Vegetation
      structure showed higher tree cover in Brisbane, but higher herb cover in Sapporo.
      In both cities over 80% of IGS was accessible or partly accessible. The amount of
      IGS we found suggests it could play a more important role than previously assumed
      for residents' recreation and nature experience as well as for fauna and flora,
      because it substantially increased the amount of potentially available greenspace
      in addition to parks and conservation greenspace. We argue that IGS has potential
      for recreation and conservation, but poses some challenges to urban planning. To
      address these challenges, we propose some directions for future research. 

PMID- 24941044
TI  - Metagenomic analysis reveals presence of Treponema denticola in a tissue biopsy
      of the Iceman.
AB  - Ancient hominoid genome studies can be regarded by definition as metagenomic
      analyses since they represent a mixture of both hominoid and microbial sequences
      in an environment. Here, we report the molecular detection of the oral spirochete
      Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year
      old Copper Age natural ice mummy. Initially, the metagenomic data of the Iceman's
      genomic survey was screened for bacterial ribosomal RNA (rRNA) specific reads.
      Through ranking the reads by abundance a relatively high number of rRNA reads
      most similar to T. denticola was detected. Mapping of the metagenome sequences
      against the T. denticola genome revealed additional reads most similar to this
      opportunistic pathogen. The DNA damage pattern of specifically mapped reads
      suggests an ancient origin of these sequences. The haematogenous spread of
      bacteria of the oral microbiome often reported in the recent literature could
      already explain the presence of metagenomic reads specific for T. denticola in
      the Iceman's bone biopsy. We extended, however, our survey to an Iceman gingival
      tissue sample and a mouth swab sample and could thereby detect T. denticola and
      Porphyrimonas gingivalis, another important member of the human commensal oral
      microflora. Taken together, this study clearly underlines the opportunity to
      detect disease-associated microorganisms when applying metagenomics-enabled
      approaches on datasets of ancient human remains.

PMID- 24941045
TI  - Helicobacter pylori induced gastric immunopathology is associated with distinct
      microbiota changes in the large intestines of long-term infected Mongolian
      gerbils.
AB  - BACKGROUND: Gastrointestinal (GI) inflammation in mice and men are frequently
      accompanied by distinct changes of the GI microbiota composition at sites of
      inflammation. Helicobacter (H.) pylori infection results in gastric
      immunopathology accompanied by colonization of stomachs with bacterial species,
      which are usually restricted to the lower intestine. Potential microbiota shifts
      distal to the inflammatory process following long-term H. pylori infection,
      however, have not been studied so far. METHODOLOGY/PRINCIPAL FINDINGS: For the
      first time, we investigated microbiota changes along the entire GI tract of
      Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT) or
      its isogenic DeltacagY mutant (MUT) strain which is defective in the type IV
      secretion system and thus unable to modulate specific host pathways.
      Comprehensive cultural analyses revealed that severe gastric diseases such as
      atrophic pangastritis and precancerous transformations were accompanied by
      elevated luminal loads of E. coli and enterococci in the caecum and together with
      Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected
      gerbils as compared to naive animals. Strikingly, molecular analyses revealed
      that Akkermansia, an uncultivable species involved in mucus degradation, was
      exclusively abundant in large intestines of H. pylori WT, but not MUT infected
      nor naive gerbils. CONCLUSION/SIGNIFICANCE: Taken together, long-term infection
      of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV
      secretion system leads to distinct shifts of the microbiota composition in the
      distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced
      immunopathogenesis of the stomach, including hypochlorhydria and
      hypergastrinemia, might trigger large intestinal microbiota changes whereas the
      exact underlying mechanisms need to be further unraveled.

PMID- 24941048
TI  - Epidemiology of hemoglobinopathies and thalassemias in individuals referred to
      the haematology research centre, Shiraz University of Medical Sciences, Shiraz,
      Iran from 2006 to 2011.
AB  - Hemoglobinopathies and thalassemias are the most frequent genetic hereditary
      disorders with an increasing global health burden, especially in low- and middle
      income countries. We aimed to determine the epidemiologic pattern of
      hemoglobinopathies and thalassemias in individuals referred to the Haematology
      Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran, which is
      the most important referral center in Southern Iran during 2006 to 2011. The most
      frequent abnormality was beta-thalassemia (beta-thal) minor (24.0%), followed by
      alpha-thalassemia (alpha-thal) trait (10.0%), hemoglobin (Hb) S trait (4.0%) and
      Hb D-Punjab trait (4.0%). Because this center is a referral center, we detected a
      higher prevalence compared to the normal population; however, these data could
      help policymakers and health service providers to better programming for
      prevention of births affected with Hb disorders.

PMID- 24941047
TI  - Arboreal ant colonies as 'hot-points' of cryptic diversity for myrmecophiles: the
      weaver ant Camponotus sp. aff. textor and its interaction network with its
      associates.
AB  - INTRODUCTION: Systematic surveys of macrofaunal diversity within ant colonies are
      lacking, particularly for ants nesting in microhabitats that are difficult to
      sample. Species associated with ants are generally small and rarely collected
      organisms, which makes them more likely to be unnoticed. We assumed that this
      tendency is greater for arthropod communities in microhabitats with low
      accessibility, such as those found in the nests of arboreal ants that may
      constitute a source of cryptic biodiversity. MATERIALS AND METHODS: We
      investigated the invertebrate diversity associated with an undescribed, but
      already threatened, Neotropical Camponotus weaver ant. As most of the common
      sampling methods used in studies of ant diversity are not suited for evaluating
      myrmecophile diversity within ant nests, we evaluated the macrofauna within ant
      nests through exhaustive colony sampling of three nests and examination of more
      than 80,000 individuals. RESULTS: We identified invertebrates from three classes
      belonging to 18 taxa, some of which were new to science, and recorded the first
      instance of the co-occurrence of two brood parasitoid wasp families attacking the
      same ant host colony. This diversity of ant associates corresponded to a highly
      complex interaction network. Agonistic interactions prevailed, but the prevalence
      of myrmecophiles was remarkably low. CONCLUSIONS: Our data support the hypothesis
      of the evolution of low virulence in a variety of symbionts associated with large
      insect societies. Because most myrmecophiles found in this work are rare,
      strictly specific, and exhibit highly specialized biology, the risk of extinction
      for these hitherto unknown invertebrates and their natural enemies is high. The
      cryptic, far unappreciated diversity within arboreal ant nests in areas at high
      risk of habitat loss qualifies these nests as 'hot-points' of biodiversity that
      urgently require special attention as a component of conservation and management
      programs.

PMID- 24941049
TI  - Pharmacogenetics of antiretroviral therapy.
AB  - INTRODUCTION: Human genetic testing is rapidly entering into most medical
      disciplines, mainly as a way to predict hereditary conditions including
      predisposition to cancers or degenerative diseases. Another area of interest for
      human genomics is to ascertain the therapeutic effect and prevent potential
      toxicities and/or drug-drug interactions of medication. AREAS COVERED: Several
      human genotypes have been associated with differences in the metabolism and
      transport of antiretroviral agents that ultimately affect drug exposure. The
      accelerated discovery of new gene mutations and polymorphisms that influence the
      effects of antiretroviral drugs provides a unique opportunity for a personalized
      medicine approach in the management of lifelong HIV therapy. EXPERT OPINION:
      Integration of human genomic screening into HIV clinical management will be cost
      effective, maximizing the benefit of drugs with the lowest risk of side effects
      for a given patient.

PMID- 24941050
TI  - Correlates of, and barriers to, Internet use among older adults.
AB  - Older adults constitute the group with the greatest increase in Internet usage in
      the past decade; however, usage varies greatly within this population. Services
      to older adults require a current understanding of Internet-use trends. This
      study utilized a quantitative survey method to examine correlates of, and
      barriers to, current Internet use in a demographically diverse county in Southern
      California. Findings indicate that the presence of a computer at home, a job
      requiring computer use, age, education, and ethnicity are important factors in
      predicting Internet use in older adults. Implications for social work practice
      with older adults is discussed. 

PMID- 24941051
TI  - Editorial.

PMID- 24941052
TI  - Gender differences in efficacy and sexual function in long-term trazodone
      treatment (preliminary results).
AB  - Objects. To evaluate the effect of trazodone on depressive or anxiety symptoms
      and sexual function depending on patient gender. Method. A total of 111 patients
      (59 men, 52 women) subjected to long-term treatment with trazodone were studied.
      The effect of the therapy was recorded according to the Clinical Global
      Impression - Severity of Illness (CGI-S) scale. The incidence of sexual
      dysfunction was assessed on the Utvalg for Kliniske Undersogelser (UKU) scale.
      Results. The effect of the therapy was similar in both genders. The incidence of
      diminished sexual desire was low and comparable in both genders; orgasmic
      dysfunctions were present only in women at the level of statistical significance.
      A positive correlation between the severity of the illness and the occurrence of
      diminished sexual desire and orgasmic dysfunction was found in women but not in
      men. Conclusion. The occurrence of sexual dysfunctions in trazodone therapy was
      lower than in population. It seems that trazodone is an effective therapy of
      depressive and anxiety symptoms in both genders and it is convenient for sexually
      active patients, because the occurrence of sexual dysfunctions was present the
      general to a low degree. 

PMID- 24941053
TI  - Comparison of pain threshold, health and functional status of females with
      fibromyalgia and multiple sclerosis: a pilot study.
AB  - Objectives. Fibromyalgia (FM) and multiple sclerosis (MS) are known to cause
      disability and have an impact on physical functioning, social functioning, and
      emotional well-being of affected individuals. The aim of this study was to
      compare pressure pain threshold, health and functional status in females with FM
      and MS who were ambulatory. Methods. Control point scores (CPS), total myalgic
      scores (TMS; using an algometer), tender point (TP) counts, and chronic
      widespread pain were assessed in females with FM and MS and in healthy age
      matched female controls. The Fibromyalgia Impact Questionnaire (FIQ), and the
      Nottingham Health Profile were performed. The Kurtzke Expanded Disability Status
      Scale (EDSS) was used to estimate the disability status of persons with MS.
      Results. Fibromyalgia patients have significantly lower CPS and TMS than MS
      patients and controls. Multiple sclerosis patients had similar CPS but
      significantly lower TMS compared to controls. Tender point counts were
      significantly higher in FM than MS patients and controls. Patients with MS had a
      higher numbers of TPs with respect to controls. Chronic widespread pain was
      reported by only three patients with MS and these patients did not meet FM
      criteria for tender point counts. Fibromyalgia patients had significantly lower
      FIQ-first item scores than MS patients. FM patients had higher NHP section scores
      in pain, social isolation, emotional reaction, sleep and energy, but similar
      physical mobility compared to MS patients. In MS patients energy and physical
      mobility dimension of NHP and FIQ-first item scores correlated with EDSS (r=0.42,
      P=0.047, r=0.83, P=0.001, and r=0.62, P=0.001, respectively). Conclusion. This
      cross-sectional study warrants further research comparing FM and MS, which share
      a lot of clinical and psychosocial features or may coexist. Chronic pain and
      related fatigue, social and emotional reactions and disability seem to be
      important components in FM, so taking care of these components, in other words a
      biopsychosocial model, may improve disease outcome and quality of life not only
      in FM but also in MS. 

PMID- 24941054
TI  - Correlation of liver dysfunction biological markers to the mood status of alcohol
      dependent individuals.
AB  - OBJECTIVE: Alcohol intake is a major cause of liver cirrhosis as well as chronic
      liver disease, and commonly coexists with mood disorders such as depression and
      anxiety. The aim of the present study was to investigate the possible correlation
      between liver dysfunction related to alcohol intake with anxiety and depressive
      like symptomatology prior to and after the detoxification period. METHODS: One
      hundred alcohol abusing/dependent subjects (81 males and 19 females) were treated
      on an inpatient basis according to a standard detoxification protocol and
      measurements of serum levels of hepatic enzymes (ASAT, ALAT, gammaGT), and
      measures of anxiety (HARS), depression (HDRS) and global functioning (GAS) were
      also obtained at baseline and at weekly intervals over a period of 4 weeks.
      RESULTS: Increased levels of hepatic enzymes were observed upon admission that
      were significantly reduced (P<0.001) following completion of the detoxification
      treatment. In addition, the psychopathological profile was improved at the end of
      the detoxification period and a significant correlation was obtained between the
      levels of hepatic enzymes and the global functioning of alcohol-dependent
      individuals. CONCLUSION: This observation further supports a relationship between
      the depressogenic action of alcohol and the disordered liver function observed in
      alcohol-dependent individuals, with possible implications in the diagnosis and
      treatment of mood disorders associated to alcohol abuse.

PMID- 24941055
TI  - Symptom control, functioning and satisfaction among Swiss patients treated with
      risperidone long-acting injectable.
AB  - OBJECTIVE: To investigate antipsychotic efficacy and tolerability of risperidone
      long-acting injectable (RLAI) in Swiss patients with schizophrenia or other
      psychotic disorders, changed directly from their previous antipsychotic
      medication. METHODS: Patients symptomatically stable for >=1 month on their
      previous medication and considered to require a treatment change, received 25 mg
      RLAI (increased to 37.5 or 50 mg, if required) every 2 weeks for 6 months.
      RESULTS: Of 60 patients enrolled (68.3% male, average age 40.4 years), most
      (81.7%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were with
      atypical antipsychotics (58.3% of patients), depot (38.3%) and conventional oral
      (13.3%) neuroleptics. Mean total PANSS scores were significantly reduced from
      baseline to treatment endpoint (76.1 vs. 64.4, P<0.001), as were all PANSS
      subscale and symptom factor scores. The CGI, GAF, and patient satisfaction with
      treatment were also significantly improved at endpoint (P<0.001). At endpoint,
      37.0% of patients rated their satisfaction as "very good" compared with only 4.3%
      at baseline. Mean scores for total ESRS and Parkinsonism subscales were
      significantly reduced at endpoint (P<0.001). CONCLUSION: Treatment with RLAI
      significantly improved disease symptoms, functioning, patient satisfaction, and
      reduced movement disorders. It provides an important option for long-term
      treatment of patients with psychotic disorders.

PMID- 24941056
TI  - Attitudes of clinicians in emergency room towards suicide.
AB  - Objective. The present study brings to focus common attitudes of clinicians
      working in the emergency room. Methods. A questionnaire was used to assess the
      attitudes of clinicians working in the emergency room. The data were subjected to
      factor analysis. Results. These clinicians show attitudes of avoidance,
      rejection, hostility, anxiety and fear, and inadequacy. They also considered the
      act of suicide as manipulative and unlawful. Conclusion. Due to various internal
      as well as external factors these medical professionals have negative attitudes
      towards suicide attempters, with a resultant low quality of care. Dealing with
      one's own anxieties over suicide and death, along with having good evaluation
      skills and a multidisciplinary approach to handle such cases, could save many
      more lives. 

PMID- 24941057
TI  - The Korean Medication Algorithm for Major Depressive Disorder (KMA-MDD): Report
      of the Korean Society of Depressive and Bipolar Disorders.
AB  - Objective. There are many differences in biological characteristics, clinical
      situations, and medical insurance systems with ethnic groups or countries. The
      Korean Society of Depressive and Bipolar Disorders decided to develop a Korean
      treatment algorithm for major depressive disorder. Methods. The Korean Medication
      Algorithm Project for Major Depressive Disorder (KMAP-MDD) was designed with the
      following principles: (1) to be an ideal algorithm, (2) to be a Korean algorithm,
      (3) to be a medication algorithm, (4) to be an evidence-based and formal
      consensus algorithm. After collecting and reviewing many literature citations and
      reports by evidence-based rule, we constructed a survey questionnaire for formal
      consensus of Korean experts. By employing panels of experts to review the
      evidence and survey results thoroughly, we used evidence-based algorithm
      development as a component of a formal consensus development process. Results. We
      developed two algorithms for the KMA-MDD: one for major depressive disorder
      without psychotic feature and the other for major depressive disorder with
      psychotic features. Clinical guidelines for the implementation of KMA-MDD were
      also developed. The KMA-MDD provides specific treatment strategies for each
      stage. Conclusions. The KMA-MDD is the first Korean algorithm for treatment of
      major depressive disorder. It is based on evidence which supports the efficacy of
      each treatment, and it has obtained the consensus of Korean experts. We hope that
      the KMA-MDD will be good practical tool for clinicians who treat major depressive
      disorder in Korea. 

PMID- 24941059
TI  - Effectiveness, tolerability and subjective well-being in patients receiving
      quetiapine: findings of a post-marketing surveillance study in schizophrenia.
AB  - Objectives. Previous studies of antipsychotics have mainly focused on efficacy
      and tolerability. However, patient subjective well-being is increasingly being
      accepted as a valid and important measure of antipsychotic treatment outcomes and
      tolerability. Methods. In this open-label, observational trial data from 1322
      outpatients with schizophrenia treated with flexibly dosed quetiapine were
      collected at baseline, Week 4 and Week 12. Patient well-being was assessed using
      Subjective Well-being under Neuroleptics (SWN-K) scale and disease severity with
      the Clinical Global Impressions-Severity of Illness (CGI-S) scale following
      quetiapine treatment. In addition, safety and tolerability were monitored
      throughout the study. Results. Quetiapine treatment, mean endpoint dose 337
      mg/day, led to a significant reduction in disease severity, with improvements in
      CGI-S score of -0.7 at Week 4 and -1.3 at Week 12 (both P<0.001). In addition,
      patients' subjective well-being was significantly improved at Week 12, with a
      mean (SD) increase from baseline in SWN-K total score of 22.9 (18.7) (P<0.001).
      Further, an improved tolerability profile compared with previous medication was
      reported. Conclusions. This study emphasises the importance of patients'
      subjective well-being and the favourable acceptability of quetiapine among
      patients with schizophrenia. 

PMID- 24941058
TI  - Does the case study have a future in the psychiatric literature?
AB  - Case studies (that is, case-based research) and their status in contemporary
      psychiatric literature are the main focus of this article. In essence, it
      evaluates the validity of such research to determine whether or not it will
      continue to be useful as a viable tool in light of the current emphasis on
      empirically validated research in the field of psychiatry. Various implications
      of the role of case studies are considered, including the ways in which the
      research might be designed to be more rigorous so that it can serve as the basis
      for drawing causal inferences in clinical cases. A discussion section highlights
      the future direction of case-based research in the professional literature and
      how it may be used to best advantage as a learning tool. 

PMID- 24941060
TI  - Medication options for treatment-resistant schizophrenia: implications for global
      mental health financing.
AB  - Treatment resistance in schizophrenia creates a persistent public health problem
      and leads to repeated hospitalization. In search for a treatment for such
      patients, psychiatrists have co-prescribed multiple psychotropic medications
      simultaneously. Such practice is based mostly on clinical experience, rather than
      research derived evidence. Such combinations may not be fully "effective" if the
      cost, adverse effect profile and the potential for noncompliance by patients
      secondary to regimen complexity are considered. Is it really wise to try these
      various combinations of costly medicines in the mental health system, which is
      already struggling with its limited resources and funding worldwide? However, if
      mental health policy makers restrict reimbursement for such "unproven"
      combinations, patients might not receive the benefits of some of these
      combinations, which are showing some promise for the treatment of resistant
      schizophrenia. 

PMID- 24941061
TI  - Coexistence of folie communiquee and folie simultanee.
AB  - Objective. The authors report a case during which they observed serious subtypes
      of induced delusional psychosis (folie communiquee and folie simultanee) without
      any common genetic background or premorbid psychosis in the case of the secondary
      patient. Method. The clinical phenomenology of the case is described. Results.
      Mild intellectual disability and environmental-psychological factors (social
      isolation and the symbiotic-like interpersonal relatedness) play an essential
      aetiological role in the case of the secondary recipient patient. Conclusion. The
      authors emphasize the importance of subclassification of induced delusional
      psychosis for further aetiological and clinical research. 

PMID- 24941062
TI  - Reboxetine may cause amenorrhea in female patients.
AB  - Objective. Reboxetine is a selective noradrenaline reuptake inhibitor (NaRI), a
      study on the effects of reboxetine on amenorrhea has not been reported in the
      literature up to now. This report describes a patient with symptoms of amenorrhea
      which is thought to be caused by reboxetine. Case. A female patient with major
      depressive disorder was given reboxetine 8 mg/day. She had experienced secondary
      amenorrhea for 3 months. The patient had no periodic irregularity before
      reboxetine use, and after reboxetine was discontinued menstruation resumed. After
      another trial with reboxetine at the optimal dose (8 mg/day, increased
      gradually), the patient reported amenorrhea again for 2 months. On discontinuing
      reboxetine, her menstrual cycle became regular again. Discussion. FSH, LH, E2 and
      prolactin levels were normal in our patient. Because amenorrhea was temporally
      related with reboxetine trials, we posit that this phenomenon may be due to side
      effects of reboxetine. This may be due to noraderenergic effects on hormonal
      function. 

PMID- 24941063
TI  - Unraveling the relative importance of oral and dermal contaminant exposure in
      reptiles: insights from studies using the western fence lizard (Sceloporus
      occidentalis).
AB  - Despite widespread recognition of significant data deficiencies, reptiles remain
      a relatively understudied taxon in ecotoxicology. To conduct ecological risk
      assessments on reptiles frequently requires using surrogate taxa such as birds,
      but recent research suggests that reptiles have significantly different exposure
      profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus
      occidentalis, to the same quantities of three model chemicals via oral (gavage)
      and dermal (ventral skin application) exposure for either 24 or 48 hours. Three
      phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and
      di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they
      represent a gradient of lipophilicity but are otherwise structurally similar.
      Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher
      concentrations in tissues than the less lipophilic DMP. Significant differences
      in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting
      that delivery to a site of action following exposure is not only a simple
      function of lipophilicity. In dermal treatments, DMP usually had fewer detections
      (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a
      requirement for uptake across the skin. In general, tissue residues were greater
      in oral treatments than dermal treatments (significant in adipose and liver
      tissue), but differences were driven strongly by differences in DMP which did not
      appear to be absorbed well across skin. When differences in tissue residue
      concentrations between oral and dermal exposure did occur, the difference was not
      drastic. Taken together these results suggest that dermal exposure should be
      considered in risk assessments for reptilian receptors. Dermal exposure may be an
      especially important route for reptiles as their ectothermic physiology
      translates to lower energetic demands and dietary exposure compared to birds and
      mammals. 

PMID- 24941064
TI  - Low prevalence of oral and nasal human papillomavirus in employees performing CO2
      laser evaporation of genital warts or loop electrode excision procedure of
      cervical dysplasia.
AB  - Risk of human papillomavirus (HPV) transmission during laser vaporisation of
      genital warts or loop electrode excision procedure is controversial. An oral
      rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure
      were collected from 287 employees at departments of dermato-venerology and
      gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with
      experience of laser treatment of genital warts as compared to 1.7% of those with
      no experience (p = 0.12). HPV prevalence was not higher in employees
      participating in electrosurgical treatment or cryotherapy of genital warts, or
      loop electrode excision procedure compared with those who did not. HPV 6 or 11
      were not detected in any samples. Hand warts after the age of 24 years was more
      common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p =
      0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health
      care personnel, however, employees at departments of dermato-venereology are at
      risk of acquiring hand warts. 

PMID- 24941065
TI  - Incidental memory of younger and older adults for objects encountered in a real
      world context.
AB  - Effects of context on the perception of, and incidental memory for, real-world
      objects have predominantly been investigated in younger individuals, under
      conditions involving a single static viewpoint. We examined the effects of prior
      object context and object familiarity on both older and younger adults'
      incidental memory for real objects encountered while they traversed a conference
      room. Recognition memory for context-typical and context-atypical objects was
      compared with a third group of unfamiliar objects that were not readily named and
      that had no strongly associated context. Both older and younger adults
      demonstrated a typicality effect, showing significantly lower 2-alternative
      forced-choice recognition of context-typical than context-atypical objects; for
      these objects, the recognition of older adults either significantly exceeded, or
      numerically surpassed, that of younger adults. Testing-awareness elevated
      recognition but did not interact with age or with object type. Older adults
      showed significantly higher recognition for context-atypical objects than for
      unfamiliar objects that had no prior strongly associated context. The observation
      of a typicality effect in both age groups is consistent with preserved semantic
      schemata processing in aging. The incidental recognition advantage of older over
      younger adults for the context-typical and context-atypical objects may reflect
      aging-related differences in goal-related processing, with older adults under
      comparatively more novel circumstances being more likely to direct their
      attention to the external environment, or age-related differences in top-down
      effortful distraction regulation, with older individuals' attention more readily
      captured by salient objects in the environment. Older adults' reduced recognition
      of unfamiliar objects compared to context-atypical objects may reflect possible
      age differences in contextually driven expectancy violations. The latter finding
      underscores the theoretical and methodological value of including a third type of
      objects--that are comparatively neutral with respect to their contextual
      associations--to help differentiate between contextual integration effects (for
      schema-consistent objects) and expectancy violations (for schema-inconsistent
      objects).

PMID- 24941066
TI  - Mutant ubiquitin UBB+1 induces mitochondrial fusion by destabilizing
      mitochondrial fission-specific proteins and confers resistance to oxidative
      stress-induced cell death in astrocytic cells.
AB  - Mutant ubiquitin UBB+1 is observed in a variety of aging-related
      neurodegenerative diseases and acts as a potent inhibitor of the ubiquitin
      proteasome system (UPS). In the present study, we investigated the relationship
      between impaired UPS (using ectopic expression of UBB+1) and mitochondrial
      dynamics in astrocytes, which are the most abundant glial cells in the central
      nervous system. Immunocytochemistry and fluorescence recovery after
      photobleaching revealed that ectopic expression of UBB+1 induced mitochondrial
      elongation. We further demonstrated that overexpression of UBB+1 destabilized
      mitochondrial fission-specific proteins including Drp1, Fis1, and OPA3, but not
      the mitochondrial fusion-specific proteins Mfn1, Mfn2, and OPA1. The reduction in
      mitochondrial fission-specific proteins by UBB+1 was prevented by inhibiting the
      26 S proteasome using chemical inhibitors, including MG132, lactacystin and
      epoxomicin. We then assessed the involvement of proteases that target
      mitochondrial proteins by using various protease inhibitors. Finally, we
      confirmed that either overexpression of UBB+1 or inhibiting the proteasome can
      protect astrocytic cells from H2O2-induced cell death compared with control
      cells. Our results suggest that UBB+1 destabilizes mitochondrial fission-specific
      proteins, leading to mitochondrial fusion and the subsequent resistance to
      oxidative stress. We therefore propose a protective role of UBB+1 overexpression
      or the proteasome inhibition in astrocytes in degenerative brains. 

PMID- 24941069
TI  - Synthesis and application of monodisperse oligo(oxyethylene)-grafted polystyrene
      resins for solid-phase organic synthesis.
AB  - In a preliminary investigation by our group, we found that poly(styrene
      oxyethylene) graft copolymers (PS-PEG), for example, TentaGel resins, are
      advantageous for gel-phase (13)C NMR spectroscopy. Because of the solution-like
      environment provided by the PS-PEG resins, good spectral quality of the attached
      moiety can be achieved, which is useful for nondestructive on-resin analysis. The
      general drawbacks of such resins are low loading capacities and the intense
      signal in the spectra resulting from the PEG linker (>50 units). Here, we
      describe the characterization of solvent-dependent swelling and reaction kinetics
      on a new type of resin for solid-phase organic synthesis (SPOS) that allows an
      accurate monitoring by gel-phase NMR without the above disadvantages. A series of
      polystyrene-oligo(oxyethylene) graft copolymers containing monodisperse PEG units
      (n = 2-12) was synthesized. A strong correlation between the linker (PEG) length
      and the line widths in the (13)C gel-phase spectra was observed, with a grafted
      PEG chain of 8 units giving similar results in terms of reactivity and gel-phase
      NMR monitoring to TentaGel resin. Multistep on-resin reaction sequences were
      performed to prove the applicability of the resins in solid-phase organic
      synthesis. 

PMID- 24941068
TI  - Computational model of erratic arrhythmias in a cardiac cell network: the role of
      gap junctions.
AB  - Cardiac morbidity and mortality increases with the population age. To investigate
      the underlying pathological mechanisms, and suggest new ways to reduce clinical
      risks, computational approaches complementing experimental and clinical
      investigations are becoming more and more important. Here we explore the possible
      processes leading to the occasional onset and termination of the (usually) non
      fatal arrhythmias widely observed in the heart. Using a computational model of a
      two-dimensional network of cardiac cells, we tested the hypothesis that an
      ischemia alters the properties of the gap junctions inside the ischemic area. In
      particular, in agreement with experimental findings, we assumed that an ischemic
      episode can alter the gap junctions of the affected cells by reducing their
      average conductance. We extended these changes to include random fluctuations
      with time, and modifications in the gap junction rectifying conductive properties
      of cells along the edges of the ischemic area. The results demonstrate how these
      alterations can qualitatively give an account of all the main types of non-fatal
      arrhythmia observed experimentally, and suggest how premature beats can be
      eliminated in three different ways: a) with a relatively small surgical
      procedure, b) with a pharmacological reduction of the rectifying conductive
      properties of the gap-junctions, and c) by pharmacologically decreasing the gap
      junction conductance. In conclusion, our model strongly supports the hypothesis
      that non-fatal arrhythmias can develop from post-ischemic alteration of the
      electrical connectivity in a relatively small area of the cardiac cell network,
      and suggests experimentally testable predictions on their possible treatments. 

PMID- 24941067
TI  - Neurological assessment and its relationship to CSF biomarkers in amateur boxers.
AB  - BACKGROUND: Mild traumatic brain injury (TBI) or concussion is common in many
      sports. Today, neuropsychological evaluation is recommended in the monitoring of
      a concussion and in return-to-play considerations. To investigate the sensitivity
      of neuropsychological assessment, we tested amateur boxers post bout and compared
      with controls. Further the relationship between neuropsychological test results
      and brain injury biomarkers in the cerebrospinal fluid (CSF) were investigated.
      METHOD: Thirty amateur boxers on high elite level with a minimum of 45 bouts and
      25 non-boxing matched controls were included. Memory tests (Rey Osterrieth
      Complex Figure, Listening Span, Digit Span, Controlled Word Association Test, and
      computerized testing of episodic memory), tests of processing speed and executive
      functions (Trail Making, Reaction Time, and Finger Tapping) were performed and
      related to previously published CSF biomarker results for the axonal injury
      marker neurofilament light (NFL). RESULTS: The neurological assessment showed no
      significant differences between boxers and controls, although elevated CSF NFL,
      as a sign of axonal injury, was detected in about 80% of the boxers 1-6 days post
      bout. The investigation of the relationship between neuropsychological evaluation
      and CSF NFL concentrations revealed that boxers with persisting NFL concentration
      elevation after at least 14 days resting time post bout, had a significantly
      poorer performance on Trail Making A (p = 0.041) and Simple Reaction Time (p =
      0.042) compared to other boxers. CONCLUSION: This is the first study showing
      traumatic axonal brain injury can be present without measureable cognitive
      impairment. The repetitive, subconcussive head trauma in amateur boxing causes
      axonal injury that can be detected with analysis of CSF NFL, but is not
      sufficient to produce impairment in memory tests, tests of processing speed, or
      executive functions. The association of prolonged CSF NFL increase in boxers with
      impairment of processing speed is an interesting observation, which needs to be
      verified in larger studies.

PMID- 24941072
TI  - Latent membrane protein 1 and the B lymphocyte-a complex relationship.
AB  - The Epstein Barr Virus (EBV)-encoded latent membrane protein 1 (LMP1) exerts
      numerous impacts on the functions of B lymphocytes, the cell type in which EBV
      establishes long-term latent infections. LMP1 expression has been implicated in
      making important contributions to a variety of human malignancies, as well as to
      autoimmune diseases. EBV also infects other types of immune cells, as well as
      nasopharyngeal epithelium, and evidence suggests that LMP1 functions may differ
      among cell types. In this review, we focus upon LMP1 functions in B cells. A
      variety of in vitro and in vivo model systems have been used by numerous groups
      of investigators to probe the ways in which LMP1 alters B-cell biology and the
      molecular mechanisms by which it exerts these effects. Here, we present a current
      overview of LMP1-mediated signaling pathways and downstream functions in B cells,
      the in vivo outcomes of LMP1 expression in model systems and humans, and the
      associations between LMP1 and human disease. 

PMID- 24941073
TI  - Complement in antibody-based tumor therapy.
AB  - Monoclonal antibodies constitute a major treatment option for many tumor
      patients. Due to their specific recognition sites in their constant Fc regions,
      antibodies are able to trigger antibody-dependent cell-mediated cytotoxicity
      (ADCC) or complement-dependent cytotoxicity (CDC). While the contribution of ADCC
      to clinical efficacy has been strengthened by observations that patients with
      favorable Fcgamma receptor polymorphisms display better response rates to
      therapeutic antibodies, the contribution of CDC to their clinical efficacy
      remains controversial. In the background of high expression of complement
      regulatory proteins on tumor cells as well as of the fact that some therapeutic
      antibodies lack the capacity to trigger efficient CDC, strategies have been
      implemented to improve either the capacity of antibodies to initiate the
      complement cascade or to interfere with tumor cells' resistance mechanisms.
      Although both strategies have demonstrated therapeutic benefit in vitro and in
      murine models, CDC-enhanced antibodies-to the best of our knowledge-have not been
      clinically tested, and evidence for the potential of CDC-optimizing approaches
      has yet to be generated in humans. Hence, the potency of complement activation
      and its impact on the clinical efficacy of therapeutic antibodies still remains
      to be elucidated in clinical trials encompassing novel complement-enhancing
      molecules. 

PMID- 24941071
TI  - LASSBio-1135: a dual TRPV1 antagonist and anti-TNF-alpha compound orally
      effective in models of inflammatory and neuropathic pain.
AB  - LASSBio-1135 is an imidazo[1,2-a]pyridine derivative with high efficacy in
      screening models of nociception and inflammation, presumed as a weak COX-2
      inhibitor. In order to tease out its mechanism of action, we investigated others
      possible target for LASSBio-1135, such as TNF-alpha and TRPV1, to better
      characterize it as a multitarget compound useful in the treatment of chronic
      pain. TRPV1 modulation was assessed in TRPV1-expressing Xenopus oocytes against
      capsaicin and low pH-induced current. Modulation of TNF-alpha production was
      evaluated in culture of macrophages stimulated with LPS. In vivo efficacy of
      LASSBio-1135 was investigated in carrageenan and partial sciatic ligation-induced
      thermal hyperalgesia and mechanical allodynia. Corroborating its previous
      demonstration of efficacy in a model of capsaicin-induced hyperalgesia, LASSBio
      1135 blocks capsaicin-elicited currents in a non-competitive way with an IC50 of
      580 nM as well as low pH-induced current at 50 uM. As an additional action,
      LASSBio-1135 inhibited TNF-alpha release in these cells stimulated by LPS with an
      IC50 of 546 nM by reducing p38 MAPK phosphorilation. Oral administration of 100
      umol x Kg(-1) LASSBio-1135 markedly reduced thermal hyperalgesia induced by
      carrageenan, however at 10 umol x Kg(-1) only a partial reduction was observed at
      the 4th h. Neutrophil recruitment and TNF-alpha production after carrageenan
      stimulus was also inhibited by the treatment with LASSBio-1135. Modulating TRPV1
      and TNF-alpha production, two key therapeutic targets of neuropathic pain, 100
      umol x Kg(-1) LASSBio-1135 was orally efficacious in reversing thermal
      hyperalgesia and mechanical allodynia produced by partial sciatic ligation 7-11
      days after surgery without provoking hyperthermia, a common side effect of TRPV1
      antagonists. In conclusion LASSBio-1135, besides being a weak COX-2 inhibitor, is
      a non-competitive TRPV1 antagonist and a TNF-alpha inhibitor. As a multitarget
      compound, LASSBio-1135 is orally efficacious in a model of neuropathic pain
      without presenting hyperthermia.

PMID- 24941074
TI  - Biological function of HLA-DO (H2-O).
AB  - HLA-DO (H2-O) is a highly conserved nonpolymorphic major histocompatibility
      complex class II (MHCII) like molecule expressed in B lymphocytes, dendritic
      cells, and thymic epithelial cells. The biological function of DO has been
      elusive. Recent studies using site-directed mutagenesis, crystallography, and
      enzyme kinetics demonstrate that DO functions strictly as an inhibitor rather
      than modifier of DM function. DO stably binds to DM at the catalytic site to
      block DM interaction with MHCII. While the new data establish the molecular
      mechanism of DO function, the reason that professional antigen-presenting cells
      (APCs) express DO to generate DO-DM complexes that are functionally inactive
      remains unclear. Despite the finding that DO inhibits DM, antigen presentation by
      H2-O-/- APCs is inefficient compared to wild-type (WT) APCs, and H2-O-/- mice are
      partially immunodeficient and spontaneously develop auto-antibodies to nuclear
      antigens. The results of functional studies raise the question of how an
      inhibitor of DM enhances antigen presentation and promotes immunity. In this
      review, we analyze the related findings from previous and recent studies. The
      integration of the all of the data allows us to propose a model explaining how DO
      enhances antigen presentation by inhibiting DM function. 

PMID- 24941075
TI  - Emerging concepts in dengue pathogenesis: interplay between plasmablasts,
      platelets, and complement in triggering vasculopathy.
AB  - Dengue is a mosquito-borne disease caused by infection with dengue virus (DENV)
      that represents a serious and expanding global health threat. Most DENV
      infections are inapparent or produce mild and self-limiting illness; however a
      significant proportion results in severe disease characterized by vasculopathy
      and plasma leakage that may culminate in shock and death. The cause of dengue
      associated vasculopathy is likely to be multifactorial but remains essentially
      unknown. Severe disease is manifest during a critical phase from 4 to 7 days
      after onset of symptoms, once the virus has disappeared from the circulation but
      before the peak of T-cell activation, suggesting that other factors mediate
      vasculopathy. Here, we present evidence for a combined role of plasmablasts,
      complement, and platelets in driving severe disease in DENV infection. Massive
      expansion of virus-specific plasmablasts peaks during the critical phase of
      infection, coincident with activation of complement and activation and depletion
      of platelets. We propose a step-wise model in which virus-specific antibodies
      produced by plasmablasts form immune complexes, leading to activation of
      complement and release of vasoactive anaphylatoxins. Platelets become activated
      through binding of complement- and antibody-coated virus, as well as direct
      binding of virus to DC-SIGN, leading to the release of inflammatory
      microparticles and cytokines and sequestration of platelets in the
      microvasculature. We suggest that the combined effects of anaphylatoxins,
      inflammatory microparticles, and platelet sequestration serve as triggers of
      vasculopathy in severe dengue. 

PMID- 24941078
TI  - Abstracts presented at the fifth symposium of the Belgian Society of Emergency
      and Disaster Medicine (BESEDIM).

PMID- 24941076
TI  - Scavenger receptor-A (CD204): a two-edged sword in health and disease.
AB  - Scavenger receptor A (SR-A), also known as the macrophage scavenger receptor and
      cluster of differentiation 204 (CD204), plays roles in lipid metabolism,
      atherogenesis, and a number of metabolic processes. However, recent evidence
      points to important roles for SR-A in inflammation, innate immunity, host
      defense, sepsis, and ischemic injury. Herein, we review the role of SR-A in
      inflammation, innate immunity, host defense, sepsis, cardiac and cerebral
      ischemic injury, Alzheimer's disease, virus recognition and uptake, bone
      metabolism, and pulmonary injury. Interestingly, SR-A is reported to be host
      protective in some disease states, but there is also compelling evidence that SR
      A plays a role in the pathophysiology of other diseases. These observations of
      both harmful and beneficial effects of SR-A are discussed here in the framework
      of inflammation, innate immunity, and endoplasmic reticulum stress. 

PMID- 24941079
TI  - Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia.
AB  - Although Streptococcus pneumoniae is a leading cause of childhood disease in
      South East Asia, little has previously been reported regarding the epidemiology
      of invasive pneumococcal disease in Malaysia and very few studies have explored
      pneumococcal epidemiology using multilocus sequence typing (MLST). Here we
      describe serotype, multilocus sequence type (ST), and penicillin susceptibility
      of thirty pneumococcal invasive disease isolates received by the University of
      Malaya Medical Centre between February 2000 and January 2007 and relate this to
      the serotypes included in current pneumococcal conjugate vaccines. A high level
      of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of
      which were not previously described) were detected from 30 isolates. Penicillin
      non-susceptible pneumococci accounted for 33% of isolates. The extent of
      molecular heterogeneity within carried and disease-causing Malaysian pneumococci
      remains unknown. Larger surveillance and epidemiological studies are now required
      in this region to provide robust evidence on which to base future vaccine policy.

PMID- 24941082
TI  - Loss-of-function mutations in APOC3 and risk of ischemic vascular disease.
AB  - BACKGROUND: High plasma levels of nonfasting triglycerides are associated with an
      increased risk of ischemic cardiovascular disease. Whether lifelong low levels of
      nonfasting triglycerides owing to mutations in the gene encoding apolipoprotein
      C3 (APOC3) are associated with a reduced risk of ischemic cardiovascular disease
      in the general population is unknown. METHODS: Using data from 75,725
      participants in two general-population studies, we first tested whether low
      levels of nonfasting triglycerides were associated with reduced risks of ischemic
      vascular disease and ischemic heart disease. Second, we tested whether loss-of
      function mutations in APOC3, which were associated with reduced levels of
      nonfasting triglycerides, were also associated with reduced risks of ischemic
      vascular disease and ischemic heart disease. During follow-up, ischemic vascular
      disease developed in 10,797 participants, and ischemic heart disease developed in
      7557 of these 10,797 participants. RESULTS: Participants with nonfasting
      triglyceride levels of less than 1.00 mmol per liter (90 mg per deciliter) had a
      significantly lower incidence of cardiovascular disease than those with levels of
      4.00 mmol per liter (350 mg per deciliter) or more (hazard ratio for ischemic
      vascular disease, 0.43; 95% confidence interval [CI], 0.35 to 0.54; hazard ratio
      for ischemic heart disease, 0.40; 95% CI, 0.31 to 0.52). Heterozygosity for loss
      of-function mutations in APOC3, as compared with no APOC3 mutations, was
      associated with a mean reduction in nonfasting triglyceride levels of 44%
      (P<0.001). The cumulative incidences of ischemic vascular disease and ischemic
      heart disease were reduced in heterozygotes as compared with noncarriers of APOC3
      mutations (P=0.009 and P=0.05, respectively), with corresponding risk reductions
      of 41% (hazard ratio, 0.59; 95% CI, 0.41 to 0.86; P=0.007) and 36% (hazard ratio,
      0.64; 95% CI, 0.41 to 0.99; P=0.04). CONCLUSIONS: Loss-of-function mutations in
      APOC3 were associated with low levels of triglycerides and a reduced risk of
      ischemic cardiovascular disease. (Funded by the European Union and others.).

PMID- 24941083
TI  - Formation of lysozyme oligomers at model cell membranes monitored with sum
      frequency generation spectroscopy.
AB  - A growing number of studies suggest that the formation of toxic oligomers,
      precursors of amyloid fibrils, is initiated at the cell membrane and not in the
      cytosolic compartments of the cell. Studies of membrane-induced protein
      oligomerization are challenging due to the difficulties of probing small numbers
      of proteins present at membrane surfaces. Here, we employ surface-sensitive
      vibrational sum frequency generation (VSFG) to investigate the secondary
      structure of lysozyme at the surface of lipid monolayers. We investigate lysozyme
      aggregation at negatively charged 1,2-dipalmitoyl-sn-glycero-3-(phospho-rac-1
      glycerol) (DPPG) lipid monolayers under different pH conditions. The changes in
      the molecular vibrations of lipids, proteins, and water as a function of pH and
      surface pressure allow us to simultaneously monitor details of the conformation
      state of lysozyme, the organization of lipids, and the state of lipid-bound
      water. At pH = 6 lysozyme induces significant disordering of the lipid layer, and
      it exists in two states: a monomeric state with a predominantly alpha-helix
      content and an oligomeric (za-mer) state. At pH <= 3, all membrane-bound lysozyme
      self-associates into oligomers characterized by an antiparallel beta-sheet
      structure. This is different from the situation in bulk solution, for which
      circular dichroism (CD) shows that the protein maintains an alpha-helix
      conformation, under both neutral and acidic pH conditions. The transition from
      monomers to oligomers is also associated with a decreased hydration of the lipid
      monolayer resulting in an increase of the lipid acyl chains ordering. The results
      indicate that oligomerization requires cooperative action between lysozyme
      incorporated into the lipid membrane and peripherally adsorbed lysozyme and is
      associated with the membrane dehydration and lipid reorganization. Membrane-bound
      oligomers with antiparallel beta-sheet structure are found to destabilize lipid
      membranes. 

PMID- 24941084
TI  - A rapid and sensitive LC-MS/MS assay for the determination of saxagliptin and its
      active metabolite 5-hydroxy saxagliptin in human plasma and its application to a
      pharmacokinetic study.
AB  - The authors proposed a simple, rapid and sensitive liquid chromatography-tandem
      mass spectrometric (LC-MS/MS) assay method for the simultaneous determination of
      saxagliptin and its active metabolite 5-hydroxy saxagliptin in human plasma. The
      developed method was fully validated as per the US FDA guidelines. The method
      utilized stable labeled isotopes saxagliptin-15 N d2 (IS1) and 5-hydroxy
      saxagliptin-15 N-d2 (IS2) as internal standards for the quantification of
      saxagliptin and 5-hydroxy saxagliptin, respectively. Analytes and the internal
      standards were extracted from human plasma by a single step solid-phase
      extraction technique without drying, evaporation and reconstitution steps. The
      optimized mobile phase was composed of 0.1% acetic acid in 5 mM ammonium acetate
      and acetonitrile (30:70, v/v) and delivered at a flow rate of 0.85 mL/min. The
      method exhibits the linear calibration range of 0.05-100 ng/mL for both the
      analytes. The precision and accuracy results for both the analytes were well
      within the acceptance limits. The different stability experiments conducted in
      aqueous samples and in matrix samples are meeting the acceptance criteria. The
      chromatographic run time was set at 1.8 min; hence more than 400 samples can be
      analyzed in a single day. 

PMID- 24941085
TI  - Two New Flavonoids and Biological Activity of Astragalus abyssinicus (Hochst.)
      Steud. ex A. Rich. Aerial Parts.
AB  - 2 new flavonoid glycosides, kaempferol 3-O-(4",6"-di-O-alpha-L-rhamnopyranosyl)
      beta-D-glucopyranoside (1) and quercetin 3-O-(4",6"-di-O-alpha-L-rhamnopyranosyl)
      beta-D-glucopyranoside (2), were isolated from the n-butanol soluble fraction of
      the methanol extract (BF) of Astragalus abyssinicus aerial parts, together with 3
      known compounds, rutin (3), kaempferol 3-O-beta-D-rutinoside (4) and 5,7,4'
      trihydroxy-3'-methoxyisoflavone (5). The structures of the isolated compounds
      were characterized on the basis of UV, NMR and negative ESI-MS analyses. The BF
      fraction showed in vitro weak antibacterial activity against Staphylococcus
      aureus, while 2 and 3 exhibited in vitro antioxidant activity higher than
      ascorbic acid using DPPH free radical scavenging activity method.

PMID- 24941086
TI  - Paclitaxel and gemcitabine combinational drug-loaded mucoadhesive delivery system
      in the treatment of colon cancers.
AB  - The combination of two different types of chemo-therapeutic drugs via
      nanocarriers is emerged as a promising strategy for treating multiple cancers.
      Such a co-delivery system will synchronize the drug exposure and synergize the
      therapeutic effects. Herein, we prepared a paclitaxel (PTX) and gemcitabine (GEM)
      loaded N-succinyl chitosan nanoparticles (NSC NP) to target colon cancer. NSC NP
      showed a pH sensitive swelling at colonic pH and exhibited a sequential release
      pattern for both the drugs. Binary drug combination exhibited a synergistic
      cytotoxicity against HT-29 colon cancer cells with a remarkable G2/M phase
      arrest. Specifically, in vivo antitumor efficacy study showed that NSC NP
      prolonged the survival time of tumor-bearing mice up to 45 days wherein 50% of
      mice were still alive. Therefore, these results suggest that co-delivery of drugs
      with a suitable delivery system could potentially improve the therapeutic
      efficacy in colon cancers. The study can be further continued by using different
      types of chemotherapeutic drugs that targets different molecular targets using pH
      sensitive nanocarriers. 

PMID- 24941081
TI  - Loss-of-function mutations in APOC3, triglycerides, and coronary disease.
AB  - BACKGROUND: Plasma triglyceride levels are heritable and are correlated with the
      risk of coronary heart disease. Sequencing of the protein-coding regions of the
      human genome (the exome) has the potential to identify rare mutations that have a
      large effect on phenotype. METHODS: We sequenced the protein-coding regions of
      18,666 genes in each of 3734 participants of European or African ancestry in the
      Exome Sequencing Project. We conducted tests to determine whether rare mutations
      in coding sequence, individually or in aggregate within a gene, were associated
      with plasma triglyceride levels. For mutations associated with triglyceride
      levels, we subsequently evaluated their association with the risk of coronary
      heart disease in 110,970 persons. RESULTS: An aggregate of rare mutations in the
      gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma
      triglyceride levels. Among the four mutations that drove this result, three were
      loss-of-function mutations: a nonsense mutation (R19X) and two splice-site
      mutations (IVS2+1G->A and IVS3+1G->T). The fourth was a missense mutation (A43T).
      Approximately 1 in 150 persons in the study was a heterozygous carrier of at
      least one of these four mutations. Triglyceride levels in the carriers were 39%
      lower than levels in noncarriers (P<1*10(-20)), and circulating levels of APOC3
      in carriers were 46% lower than levels in noncarriers (P=8*10(-10)). The risk of
      coronary heart disease among 498 carriers of any rare APOC3 mutation was 40%
      lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence
      interval, 0.47 to 0.75; P=4*10(-6)). CONCLUSIONS: Rare mutations that disrupt
      APOC3 function were associated with lower levels of plasma triglycerides and
      APOC3. Carriers of these mutations were found to have a reduced risk of coronary
      heart disease. (Funded by the National Heart, Lung, and Blood Institute and
      others.).

PMID- 24941088
TI  - Editorial.

PMID- 24941089
TI  - The effects of nefazodone on sleep in depressed patients and healthy controls.
AB  - This paper briefly reviews the effects of antidepressants on sleep, and
      highlights recent studies on the effects of nefazodone on sleep in healthy adults
      and those with major depressive disorders. Studies indicate significant
      improvement in sleep quality, decreased light sleep, and a reduction in nocturnal
      awakenings on nefazodone with minimal effect on REM sleep. The clinical relevance
      of these sleep findings is also discussed. 

PMID- 24941087
TI  - Protective Effects of Gallic Acid against Streptozotocin-induced Oxidative Damage
      in Rat Striatum.
AB  - The present study aimed to investigate the protective effects of gallic acid (GA)
      against ICV STZ-induced oxidative damage in the rat striatum. Animals were
      randomly divided into 4 groups (8 each). Group 1 (Sham), were injected ICV on day
      1 and 3 with artificial CSF and treated with normal saline (2 ml/kg, p.o.). Group
      2 (sham+GA), were injected ICV on day 1 and 3 with artificial CSF and treated
      with GA (30 mg/kg, p.o.) for 26 days. Group 3 (lesion) were injected with ICV-STZ
      (3 mg/kg bilaterally, on day 1 and 3) and received normal saline (2 ml/kg, p.o.)
      as vehicle. Group 4 (lesion+GA), were injected with ICV-STZ (3 mg/kg bilaterally,
      on day 1 and 3) and treated with gallic acid (30 mg/kg, p.o.) once daily for 26
      days starting 5 days before the first injection of ICV STZ. The homogenized
      striatum was used for measuring thiobarbituric acid reactive species (TBARS) and
      total thiol contents, glutathione peroxidase (GPx), catalase (CAT), and
      superoxide dismutase (SOD) activities. The results showed that ICV STZ-injection
      increased the level of TBARS (+69.3%) and decreased total thiol concentration (
      48.8%), GPx (-47.3%), CAT (-47.1%) and SOD (-30.7%) activities. In contrast,
      chronic administration of GA significantly prevented the biochemical alterations
      in the ICV-STZ rats. These findings highlight the beneficial role of GA via
      enhancement of cerebral antioxidant defense system. 

PMID- 24941090
TI  - AIDS and psychiatry, revisited.
AB  - The psychiatry of HW and AIDS is a subject that now receives little attention but
      is still relevant to clinical practice. The mechanism of the HW assault on the
      brain is still not clearly understood, although early detection of central
      nervous system involvement is becoming easier with neuropsychological assessment.
      It has been suggested that HN has brain specificity, with patients presenting
      with cerebral problems without other physical signs. It is possible that AIDS may
      present with psychiatric symptoms. The mechanism of the damage to the CNS remains
      unclear. 

PMID- 24941091
TI  - Aggressive behaviour in the elderly.
AB  - In this paper, the literature on aggressive behaviour in the elderly is reviewed,
      with emphasis on: definition; study samples; patient groups; study designs and
      methodology; data collection; instruments used to measure aggressive behaviour;
      social, clinical, demographic and biological correlates; prevalence and rates;
      precipitants; outcome; site; timing; daily and seasonal variation; patterns of
      usage of hospitals and other institutions; stuffing levels, staff morale, staff
      attitudes, staff training and other staffing factors. 

PMID- 24941092
TI  - Patient satisfaction and acceptability of long-term treatment with quetiapine.
AB  - Satisfaction with, and subjective tolerability of, antipsychotic medication have
      emerged as important factors in determining treatment compliance and eventual
      outcome in the management of psychotic disorders. The acceptability of long-term
      treatment with quetiapine, an atypical antipsychotic agent with a lower incidence
      of extrapyramidal effects than standard therapy, was examined in this open-label,
      multicentre study of patient satisfaction. One hundred and twenty-nine patients
      with major psychiatric disorders, who had each been receiving quetiapine for at
      least 6 months in open-label extension studies, were asked to complete a 7-item
      questionnaire concerning subjective experience and satisfaction with treatment.
      Over 75% of respondents indicated that they were either "very" or "extremely"
      satisfied with their antipsychotic medication while 73.7% indicated that, over
      the last month, they regarded their antipsychotic medication to have been "very"
      or "extremely" helpful. Subjectively reported side-effects were uncommon, with
      74.4% of patients reporting no side-effects, 23.3% mild side-effects and only
      2.3% moderate side-effects. There were no unambiguous reports of extrapyramidal
      symptoms. An overwhelming majority of patients (114/118; 96.6%) reported that
      they preferred quetiapine to previous antipsychotic medications, the predominant
      reasons being their perceptions of better tolerability and greater efficacy.
      Patients also identified improvements in quality of life and their activities of
      daily living. These positive evaluations appeared to be reflected in the high
      proportion of respondents who indicated a readiness to continue quetiapine
      treatment. This study indicates that the combination of efficacy and a favourable
      tolerability profile shown by quetiapine may result in benefits that are evident
      to the patient and may be reflected in high levels of patient satisfaction and
      acceptance of treatment. By improving compliance with treatment, these benefits
      may also enhance clinical outcome. 

PMID- 24941093
TI  - Long term efficacy of paroxetine in major depression: A study with plasma levels.
AB  - Depressive disorders can be regarded as recurrent and chronic conditions that may
      reduce the quality of life and work output of patients. Data on the long-term
      efficacy of paroxetine appear to indicate that it is an effective maintenance
      treatment. Our aim was to measure paroxetine concentrations in plasma in order to
      optimize its clinical efficacy and tolerability during long-term treatment. We
      studied 35 patients aged 23-70 years, suffering from Major Depressive Disorder
      (recurrent). These patients received 10-50 mg of paroxetine once a day for one
      year; they were evaluated at baseline, after 2 weeks and then after 1,2,6,9 and
      12 months by BPRS, HRS-D and HRS-A rating scales, and at the same time, any side
      effects were assessed and samples for paroxetine plasma determination were also
      collected. Results confirmed the efficacy and tolerability of paroxetine for long
      term treatment. We observed a curvilinear relationship between plasma paroxetine
      levels and improvement on the HRS-D with greater clinical amelioration at plasma
      levels between 20 and 70 ng/ml. 

PMID- 24941094
TI  - Use and misuse: Antidepressants in general practice.
AB  - Depressive disorders are the most common psychiatric illnesses encountered in
      general practice. The majority of cases are managed exclusively by GPs,
      prescribing antidepressant medications with or without concurrent counselling or
      other treatments. There is persistent evidence that in relation to existing
      treatment guidelines, GPs prescribe antidepressants at inadequate doses for
      inadequate periods. The Dorset Antidepressant Side-Effects Initiative was
      designed to discover some of the issues that influence GPs' prescribing of
      antidepressants. Whilst results indicate that GPs have reasonably good
      understanding of the characteristics of the two main classes of antidepressant
      medications, they are much more likely to underprescribe older tricyclics than
      SSRIs. The differing side-effect profiles of these classes of antidepressant play
      a significant role in prescribing behaviour. However, the choice of
      antidepressant is also influenced by the age of the GP, and the type of drug
      prescribed influences the way in which the GP manages complaints of adverse
      effects. 

PMID- 24941095
TI  - The use of antiepileptic medication in a population-based cohort of adults with
      learning disability and epilepsy.
AB  - The purpose of the current study was to assess the trend of antiepileptic drug
      use in a sample of 143 adults with learning disability and epilepsy in one health
      district. Information on the dose and serum level of antiepileptic drugs received
      by the subjects, their demographic data and the epilepsy-related data were
      gathered from the medical case-notes, examination of subjects and interview with
      the carers. Sixty (42% of the cohort) subjects received polytherapy of
      antiepileptic medication. The use of polytherapy was significantly associated
      with being female, longer duration of epilepsy, multiple-seizure type, and active
      epilepsy (i.e. seizure during the previous 12-month period). Of the cohort, 52%
      receivd sodium valproate, 38.5% received carbamazepine, 29% phenytoin, 11%
      lamotrigine and 11% primidone. The majority of subjects received antiepileptic
      drugs within the BNF-recommended range; however, 38% of the subjects receiving
      carbamazepine had a lower dose than that recommended in the BNF. The serum levels
      of most antiepileptic drugs were within the local laboratory reference range,
      except that in 39% of cases the phenytoin level was below the local reference
      range. No statistically significant difference was observed in the use of
      different antiepileptic drugs and the rate of mental disorder in the cohort,
      although the subjects receiving lamotrigine and primidone showed more behavioural
      problems. Similarly, no significant association was observed between the seizure
      types and the use of different antiepileptic medications. 

PMID- 24941096
TI  - Zuclopenthixol acetate (Clopixol Acuphase) for rapid sedation.
AB  - This case report documents the effects of accidental intravenous administration
      of zuclopenthixol acetate and briefly discusses its appropriate use in the
      management of psychiatric emergencies. 

PMID- 24941097
TI  - Atypical eating disorder in a male patient.
AB  - In the literature there is evidence that a substantial proportion of patients
      with bulimia nervosa can be helped by cognitive behavioural self-help manuals. As
      there are no specific recommendations or strategies for the treatment of males
      with eating disorders we were therefore especially interested in the way a man
      might deal with such a self-help manual. In this case the book Getting better
      bit(e) by bit(e) by Treasure and Schmidt (also available in German translation)
      was given to a young man with an atypical eating disorder (atypical anorexia
      nervosa according to ICD-10). The patient was offered a maximum of 16 short
      visits and was seen by a first-year psychiatry resident. Treatment with this self
      help manual was effective and the patient succeeded in changing his former eating
      behaviour. The case report provides preliminary evidence that a self-help manual
      may be a useful addition to the range of possible interventions in the treatment
      of eating disorders in men. Self-help manuals are less intensive and less costly
      than other forms of treatment and might be the lowest-step intervention in a
      stepped-care approach to treatment. 

PMID- 24941098
TI  - Mirtazapine effectiveness in a patient with refractory psychotic depression.
AB  - The author describes a patient with recurrent depression, according to DSM-IV
      diagnostic criteria. The features were of a delusional depressive episode lasting
      5 years, associated with severe impairment of psychosocial functioning. The
      patient also had chronic hepatitis, of unknown aetiology, and portal hypertension
      with some high gastrointestinal bleeding episodes. The depressive episode had
      been treated unsuccessfully with therapeutic doses of imipramine and lithium
      augmentation associated with haloperidol and, afterwards, with risperidone.
      Mirtazapine was introduced, coadministered with haloperidol and after 8 weeks
      there was an improvement in delusional depressive and other negative symptoms.
      The patient remained well for 9 months. This case indicates that mirtazapine is
      an option for patients with psychotic depression who are refractive to tricyclic
      antidepressants. Mirtazapine is also a safe drug, well tolerated in this severe
      clinical condition. 

PMID- 24941099
TI  - A Patient Who Changed my Practice.
AB  - The patient in this paper illustrated the importance of the psychological
      manifestations of physical illness and a doctor's need to treat these within a
      medical model. She also highlighted the shortcomings of medical teaching to the
      undergraduate and career advice to postgraduate. 

PMID- 24941102
TI  - Statement.

PMID- 24941103
TI  - Sampling and analysis of metabolomes in biological fluids.
AB  - Metabolome analysis involves the study of small molecules that are involved in
      the metabolic responses that occur through patho-physiological changes caused by
      genetic stimuli or chemical agents. Qualitative and quantitative metabolome
      analyses are used for the diagnosis of various diseases or chemical exposure.
      This article presents an overview of the different analytical methods available
      for performing the determination of the metabolome, including sampling, sample
      preparation and processing and interpretation of data. Critical comments are
      aimed at emphasizing the extraction methods as well as the biological samples
      used for metabolome analysis and data processing. 

PMID- 24941105
TI  - A highly selective colorimetric chemosensor for cobalt(II) ions based on a
      tripodal amide ligand.
AB  - A tripodal amide based ligand, tris-{(2-carbamoyl-5-carbomethoxy-pyridine)-2
      ethyl}amine (H3L, 1), was synthesized and structurally characterized by single
      crystal X-ray diffraction. Investigation of the cation recognition behavior
      showed that the ligand has selective colorimetric sensing properties for
      cobalt(II) ions by an obvious color change from colorless to yellow. To
      investigate the sensing mechanism of H3L for Co(2+) ions, UV-vis absorption
      spectroscopy and single-crystal structural analysis were performed. The mixture
      of the ligand and cobalt(II) ions displayed selective colorimetric sensing
      properties for weak acid anions, such as CO3(2-), Ac(-), HCO3(-), SO3(2-), and
      PO4(3-). Detailed (1)H NMR experiments revealed that the basicity of the anions
      played an important role in the intensity of the interaction between the ligand
      and anions. The structures of compounds CoL (2), Co-Ac-HL (3), H4L-NO3 (4), and
      H4L-ClO4 (5) were also determined by single crystal diffraction studies.

PMID- 24941104
TI  - Preparation and layer-by-layer solution deposition of Cu(In,Ga)O2 nanoparticles
      with conversion to Cu(In,Ga)S2 films.
AB  - We present a method of Cu(In,Ga)S2 (CIGS) thin film formation via conversion of
      layer-by-layer (LbL) assembled Cu-In-Ga oxide (CIGO) nanoparticles and
      polyelectrolytes. CIGO nanoparticles were created via a novel flame-spray
      pyrolysis method using metal nitrate precursors, subsequently coated with
      polyallylamine (PAH), and dispersed in aqueous solution. Multilayer films were
      assembled by alternately dipping quartz, Si, and/or Mo substrates into a solution
      of either polydopamine (PDA) or polystyrenesulfonate (PSS) and then in the CIGO
      PAH dispersion to fabricate films as thick as 1-2 microns. PSS/CIGO-PAH films
      were found to be inadequate due to weak adhesion to the Si and Mo substrates,
      excessive particle diffusion during sulfurization, and mechanical softness ill
      suited to further processing. PDA/CIGO-PAH films, in contrast, were more
      mechanically robust and more tolerant of high temperature processing. After LbL
      deposition, films were oxidized to remove polymer and sulfurized at high
      temperature under flowing hydrogen sulfide to convert CIGO to CIGS. Complete film
      conversion from the oxide to the sulfide is confirmed by X-ray diffraction
      characterization. 

PMID- 24941106
TI  - Heart rate response and parasympathetic modulation during recovery from exercise
      in boys and men.
AB  - The purpose of this study was to examine the influence of postexercise
      parasympathetic modulation, measured by heart rate variability (HRV), on heart
      rate recovery (HRR) in boys (n = 13, 10.1 +/- 0.8 years) and men (n = 13, 23.9 +/
      1.5 years) following maximal and submaximal exercise. Subjects completed 10 min
      of supine rest, followed by graded exercise on a cycle ergometer to maximal
      effort. On a separate day, subjects exercised at an intensity equivalent to
      ventilatory threshold. Immediately following both exercise bouts, 1-min HRR was
      assessed in the supine position. HRV was analyzed under controlled breathing
      during the final 5 min of rest and recovery in the time and frequency domains and
      transformed to natural log (ln) values. Boys had a greater 1-min HRR than men
      following maximal (58 +/- 8 vs. 47 +/- 11 beats.min(-1)) and submaximal (59 +/- 8
      vs. 47 +/- 15 beats.min(-1)) exercise (p < 0.05). Following maximal exercise,
      boys had greater ln root mean square successive differences in R-R intervals
      (2.52 +/- 0.95 ms), ln standard deviation of NN intervals (3.34 +/- 0.57 ms), ln
      high-frequency power (4.32 +/- 2.00 ms(2)), and ln low-frequency power (4.98 +/-
      1.17 ms(2)) than men (1.33 +/- 0.37 ms, 2.52 +/- 0.24 ms, 1.32 +/- 1.06 ms(2) and
      2.80 +/- 0.74 ms(2), respectively) (p < 0.05). There were no differences in any
      HRV variables between groups following submaximal exercise (p > 0.05). In
      conclusion, it appears that greater parasympathetic modulation accounts for
      greater HRR following maximal exercise in boys versus men. Although submaximal
      HRR was greater in boys, parasympathetic responses were similar between groups. 

PMID- 24941107
TI  - Temporal changes in ERK phosphorylation are harmonious with 4E-BP1, but not
      p70S6K, during clenbuterol-induced hypertrophy in the rat gastrocnemius.
AB  - Extracellular signal-regulated kinase (ERK) is required for clenbuterol (CB)
      dependent fast-type myofibril enlargement; however, its contribution to
      translation control is unclear. ERK mediates translational regulation through
      mammalian target of rapamycin complex 1 (mTORC1) activation and (or) mTORC1
      independent pathways. In this study, we aimed to investigate the role of ERK in
      translational control during CB-induced muscular hypertrophy by measuring time
      dependent changes in the phosphorylation statuses of ERK, p70 ribosomal S6 kinase
      (p70S6K; an indicator of mTORC1 activity), 4E-binding protein 1 (4E-BP1),
      eukaryotic elongation factor 2 (eEF2), and other related signaling molecules in
      rat gastrocnemius muscles. Five-day administration of CB induced phenotypes
      associated with muscular hypertrophy (significant increases in wet weight and
      isometric ankle flexion torque in the gastrocnemius muscle), but was not
      accompanied by elevated ERK or p70S6K phosphorylation. One-day administration of
      CB caused significant increases in the phosphorylation of ERK, p70S6K, and 4E
      BP1. In contrast, 3-day administration of CB caused significant increases in the
      phosphorylation of ERK and 4E-BP1, but not p70S6K. In addition, positive
      correlations were observed between ERK and 4E-BP1 on days 1 and 3, whereas a
      correlation between ERK and p70S6K was only observed on day 1. eEF2
      phosphorylation was unchanged on both days 1 and 3. These findings suggest that
      ERK accelerates the initiation of translation, but does not support the
      involvement of ERK in translational elongation. Furthermore, ERK may play a major
      role in promoting translational initiation by mediating the phosphorylation of 4E
      BP1, and may contribute to the initial activation of mTORC1 during CB
      administration. 

PMID- 24941108
TI  - Specific visualization and identification of phosphoproteome in gels.
AB  - The applicability of gel-based proteomic strategies in phosphoproteomics has been
      largely limited by the lack of technologies for specific detection of
      phosphoproteins in gels. Here for the first time we report a strategy for
      simultaneous visualization and identification of phosphoproteome in gels (VIPing)
      through coupling specific detection of phosphoproteins with protein
      identification and phosphorylation site mapping by tandem mass spectrometry. The
      core of the strategy is a novel compound multifunctionalized with a titanium
      ion(IV) for outstanding selectivity toward phosphorylated residues, a fluorophore
      for visualization, and a biotin group for phosphopeptide enrichment. The
      sensitivity and specificity of the VIPing strategy was demonstrated using
      standard protein mixtures and complex cell extracts, and the method was applied
      to study the phosphorylation changes of an essential tyrosine kinase Syk and
      interacting proteins upon B-cell stimulation. The novel technique provides a
      powerful platform for gel-based phosphoproteomic studies. 

PMID- 24941109
TI  - Implementation of a continuous quality improvement program reduces the occurrence
      of peritonitis in PD.
AB  - OBJECTIVE: To investigate the causes of peritonitis in patients with peritoneal
      dialysis (PD) using continuous quality improvement (CQI) to develop effective
      interventions and reduce the occurrence of peritonitis. METHODS: A quality
      control team consisting of 10 members, including the department head, four
      nephrologists and four nurses, all specialized in PD care, and the head nurse,
      was established at the Peritoneal Dialysis Center of the Third Xiangya Hospital
      of Central South University. All patients with peritonitis occurring between 1
      July 2010 and 31 December 2011 (pre-CQI period) were analyzed and compared with
      data obtained between January 2012 (implementation of CQI) and March 2013 to
      investigate possible causes of peritonitis and to develop corresponding
      interventions. Fishbone analysis, including laboratory parameters, was carried
      out monthly. RESULTS: Gastrointestinal tract dysfunction, nonstandard procedures
      and malnutrition were found to be the top three risk factors for peritonitis.
      Gastrointestinal tract dysfunction was the likely cause of peritonitis in 42.8%
      of the subjects before CQI and 36.0% after CQI (p<0.05). Nonstandard procedures
      were the cause of peritonitis in 33.3% of the subjects before CQI and 24.0% after
      CQI (p<0.05). The overall incidence of peritonitis reduced from once every 40.1
      patient months before the CQI to once every 70.8 patient months after CQI
      (p<0.05). The incidence of Gram-positive bacteria peritonitis reduced from once
      every 96.9 patients per month before CQI to once every 209.1 patient months after
      CQI (p<0.05), whereas the incidence of Gram-negative bacteria peritonitis reduced
      from once every 234.2 patient months before CQI to once every 292.8 patient
      months after CQI. CONCLUSION: CQI can effectively reduce the occurrence of PD
      related peritonitis.

PMID- 24941110
TI  - Synthesis and reactivity studies of a tin(II) corrole complex.
AB  - A series of tris(pentafluorophenyl)corrole (TPFC) tin(IV) and tin(II) complexes
      were prepared and studied by various characterization techniques including (1)H,
      (19)F, and (119)Sn NMR and UV-vis spectroscopy, mass spectrometry, and single
      crystal X-ray diffraction. The unusual 4-coordinate, monomeric, divalent tin(II)
      complex [(TPFC)Sn(II)](-) (2a) showed highly efficient reactivity toward alkenes
      and alkyl halides via a nucleophilic addition pathway leading to the quantitative
      formation of alkyl stannyl corrole compounds. DFT calculations confirmed the
      divalent nature of the tin center in 2a, and an NBO analysis showed about 99.99%
      Sn lone pair character, of which 83.6% was Sn 5s and 16.35% was Sn 5p character. 

PMID- 24941111
TI  - Pen-2 is essential for gamma-secretase complex stability and trafficking but
      partially dispensable for endoproteolysis.
AB  - The 19-transmembrane gamma-secretase complex generates the amyloid beta-peptide
      of Alzheimer's disease by intramembrane proteolysis of the beta-amyloid precursor
      protein. This complex is comprised of presenilin, Aph1, nicastrin, and Pen-2. The
      exact function and mechanism of the highly conserved Pen-2 subunit remain poorly
      understood. Using systematic mutagenesis, we confirm and extend our understanding
      of which key regions and specific residues play roles in various aspects of gamma
      secretase function, including maturation, localization, and activity, but not
      processivity. In general, mutations (1) within the first half of transmembrane
      domain (TMD) 1 of Pen-2 decreased PS1 endoproteolysis and gamma-secretase
      proteolytic activity, (2) within the second half of TMD1 increased proteolytic
      activity, (3) within the cytosolic loop region decreased proteolytic activity,
      (4) within TMD2 decreased PS1 endoproteolysis, (5) within the first half of TMD2
      decreased proteolytic activity, and (6) within C-terminal residues decreased
      proteolytic activity. Specific mutational effects included N33A in TMD1 causing
      an increase in gamma-secretase complexes at the cell surface and a modest
      decrease in stability and the previously unreported I53A mutation in the loop
      region reducing stability 10-fold and proteolytic activity by half. In addition,
      we confirm that minor PS1 endoproteolysis can occur in the complete absence of
      Pen-2. Together, these data suggest that rather than solely being a catalyst for
      gamma-secretase endoproteolysis, Pen-2 may also stabilize the complex prior to
      PS1 endoproteolysis, allowing time for full assembly and proper trafficking. 

PMID- 24941113
TI  - Penifupyrone, a new cytotoxic funicone derivative from the endophytic fungus
      Penicillium sp. HSZ-43.
AB  - Penifupyrone (1), a new funicone derivative, has been isolated from the
      endophytic fungus Penicillium sp. HSZ-43, along with three known analogues,
      funicone (2), deoxyfunicone (3) and 3-O-methylfunicone (4). These structures were
      identified by using spectroscopic methods, including UV, MS, 1D and 2D NMR
      experiments. The structure of 1 was confirmed by single-crystal X-ray diffraction
      analysis. All the isolated compounds were evaluated for cytotoxicity against
      human oral epidermoid carcinoma KB cells, and compound 1 exhibited moderate
      cytotoxic activity with IC50 value of 4.7 MUM. 

PMID- 24941112
TI  - Early-life environmental variation affects intestinal microbiota and immune
      development in new-born piglets.
AB  - BACKGROUND: Early-life environmental variation affects gut microbial colonization
      and immune competence development; however, the timing and additional specifics
      of these processes are unknown. The impact of early-life environmental
      variations, as experienced under real life circumstances, on gut microbial
      colonization and immune development has not been studied extensively so far. We
      designed a study to investigate environmental variation, experienced early after
      birth, to gut microbial colonization and intestinal immune development.
      METHODOLOGY/PRINCIPAL FINDINGS: To investigate effects of early-life
      environmental changes, the piglets of 16 piglet litters were divided into 3
      groups per litter and experimentally treated on day 4 after birth. During the
      course of the experiment, the piglets were kept with their mother sow. Group 1
      was not treated, group 2 was treated with an antibiotic, and group 3 was treated
      with an antibiotic and simultaneously exposed to several routine, but stressful
      management procedures, including docking, clipping and weighing. Thereafter,
      treatment effects were measured at day 8 after birth in 16 piglets per treatment
      group by community-scale analysis of gut microbiota and genome-wide intestinal
      transcriptome profiling. We observed that the applied antibiotic treatment
      affected the composition and diversity of gut microbiota and reduced the
      expression of a large number of immune-related processes. The effect of
      management procedures on top of the use of an antibiotic was limited.
      CONCLUSIONS/SIGNIFICANCE: We provide direct evidence that different early-life
      conditions, specifically focusing on antibiotic treatment and exposure to stress,
      affect gut microbial colonization and intestinal immune development. This
      reinforces the notion that the early phase of life is critical for intestinal
      immune development, also under regular production circumstances.

PMID- 24941114
TI  - Evaluation of bias-variance trade-off for commonly used post-summarizing
      normalization procedures in large-scale gene expression studies.
AB  - Normalization procedures are widely used in high-throughput genomic data analyses
      to remove various technological noise and variations. They are known to have
      profound impact to the subsequent gene differential expression analysis. Although
      there has been some research in evaluating different normalization procedures,
      few attempts have been made to systematically evaluate the gene detection
      performances of normalization procedures from the bias-variance trade-off point
      of view, especially with strong gene differentiation effects and large sample
      size. In this paper, we conduct a thorough study to evaluate the effects of
      normalization procedures combined with several commonly used statistical tests
      and MTPs under different configurations of effect size and sample size. We
      conduct theoretical evaluation based on a random effect model, as well as
      simulation and biological data analyses to verify the results. Based on our
      findings, we provide some practical guidance for selecting a suitable
      normalization procedure under different scenarios. 

PMID- 24941116
TI  - NRT test in auditory neuropathy patients with cochlear implants.
AB  - CONCLUSION: In patients with auditory neuropathy (AN), waveforms of neural
      response telemetry (NRT) could be present, showing characteristics of low
      incidence, low differentiation, and large variation. OBJECTIVE: To study the
      characteristics of NRT in AN patients who had received cochlear implants (CIs).
      METHODS: NRT data for seven AN patients who had received Nucleus CIs were
      retrospectively analyzed. Twenty-one CI implantees with sensorineural hearing
      loss (SNHL) were included as the control group. The incidence of electrically
      evoked compound action potentials (ECAPs), threshold of wave N1, and amplitude of
      N1-P2 in the AN group were analyzed and compared between groups. RESULTS: The
      intraoperative incidence of valid ECAPs in the AN group was 42.9%, and the
      postoperative incidence was 66.7%, both of which were lower than those in the
      SNHL group, which were 95.2% and 100%, respectively. NRT in the AN group showed
      larger variation and lower differentiation than in the SNHL group. Wilcoxon's non
      parametric test results indicated no significant difference between AN and SNHL
      groups in either the threshold of ECAP or N1-P2 amplitude.

PMID- 24941117
TI  - Analysis of common deafness gene mutations in deaf people from unique ethnic
      groups in Gansu Province, China.
AB  - CONCLUSIONS: The GJB2 gene mutation characteristic of Dongxiang was the
      interaction result of ethnic background and geographical environment, and Yugur
      exhibited the typical founder effect. The SLC26A4 gene mutation characteristic of
      Dongxiang was related to caucasian backgrounds and selection of purpose exons,
      i.e. ethnic background and the penetrance of ethnic specificity caused the low
      mtDNA1555A>G mutation frequency in Dongxiang. OBJECTIVES: To determine the
      prevalence of GJB2 and SLC26A4 genes and mtDNA1555A>G mutations and analyze the
      ethnic specificity in the non-syndromic sensorineural hearing loss (NSHL) of
      unique ethnic groups in Gansu Province. METHODS: Peripheral blood samples were
      obtained from Dongxiang, Yugur, Bonan, and ethnic Han groups with moderately
      severe to profound NSHL in Gansu Province. Bidirectional sequencing (or enzyme
      digestion) was applied to identify the sequence variations. RESULTS: The
      pathogenic allele frequency of the three gene mutations was different. The
      frequency of the GJB2 gene among the Dongxiang, Yugur, Bonan, and ethnic Han
      groups was 9.03%, 12.5%, 5.88%, and 12.17%, respectively. No difference was found
      between the ethnic groups. The frequencies of the SLC26A4 genes were 3.23%,
      8.33%, 0%, and 9.81%, respectively. The mutation frequency of mtDNA1555A>G was
      0%, 0%, 0%, and 6.03%, respectively. No difference was found between the ethnic
      groups, except for the Dongxiang and ethnic Han groups, both in SLC26A4 gene and
      mtDNA1555A>G.

PMID- 24941115
TI  - Degree of glutathione deficiency and redox imbalance depend on subtype of
      mitochondrial disease and clinical status.
AB  - Mitochondrial disorders are associated with decreased energy production and redox
      imbalance. Glutathione plays a central role in redox signaling and protecting
      cells from oxidative damage. In order to understand the consequences of
      mitochondrial dysfunction on in vivo redox status, and to determine how this
      varies by mitochondrial disease subtype and clinical severity, we used a
      sensitive tandem mass spectrometry assay to precisely quantify whole blood
      reduced (GSH) and oxidized (GSSG) glutathione levels in a large cohort of
      mitochondrial disorder patients. Glutathione redox potential was calculated using
      the Nernst equation. Compared to healthy controls (n = 59), mitochondrial disease
      patients (n = 58) as a group showed significant redox imbalance (redox potential 
      251 mV +/- 9.7, p<0.0001) with an increased level of oxidation by ~ 9 mV compared
      to controls (-260 mV +/- 6.4). Underlying this abnormality were significantly
      lower whole blood GSH levels (p = 0.0008) and GSH/GSSG ratio (p = 0.0002), and
      significantly higher GSSG levels (p<0.0001) in mitochondrial disease patients
      compared to controls. Redox potential was significantly more oxidized in all
      mitochondrial disease subgroups including Leigh syndrome (n = 15), electron
      transport chain abnormalities (n = 10), mitochondrial encephalomyopathy, lactic
      acidosis and stroke-like episodes (n = 8), mtDNA deletion syndrome (n = 7), mtDNA
      depletion syndrome (n = 7), and miscellaneous other mitochondrial disorders (n =
      11). Patients hospitalized in metabolic crisis (n = 7) showed the greatest degree
      of redox imbalance at -242 mV +/- 7. Peripheral whole blood GSH and GSSG levels
      are promising biomarkers of mitochondrial dysfunction, and may give insights into
      the contribution of oxidative stress to the pathophysiology of the various
      mitochondrial disorders. In particular, evaluation of redox potential may be
      useful in monitoring of clinical status or response to redox-modulating therapies
      in clinical trials.

PMID- 24941121
TI  - Current guidelines for management of severe hand injuries.
AB  - BACKGROUND: Severe, multitissue hand injuries constitute a serious problem of the
      modern world. Despite investing significant funds in their management these
      injuries often exclude young people from professional life. It is often due to
      improper management conducted by untrained personnel lacking appropriate
      instruments. The goal of this work is to review the literature on the problem and
      attempt to organize this information. MATERIAL/METHODS: A review of available
      literature on mutilating hand trauma, amputations in the hand region,
      replantation and scales used for assessment of the severity of injury and hand
      function, both in Poland and internationally. RESULTS: Hand injuries may be
      managed through three approaches: concomitant definitive, delayed and secondary.
      The best results are achieved through the first approach. However sometimes, due
      to the character of injury or lack of trained personnel, the team is forced to
      apply temporary dressing and, subsequently, initiate complex further management.
      HISS scale is a useful tool allowing for precise determination of the severity of
      injury and, used together with DASH questionnaire, prediction of long-term
      treatment outcome. CONCLUSIONS: Necessary changes need to be implemented in the
      healthcare system in order to achieve better results of treatment of severe hand
      injuries. Proper guidelines for everyday practice should be also introduced.
      Changes should encompass precise determination of competences of individual
      centers as well as the mode and indications for patient transport between them.
      Training of doctors should be modified in such way to ensure that at least one
      person in each center would be capable of performing proper immediate management
      of such injuries, making further treatment possible. At the same time, financing,
      as a strong motivator, should promote appropriate management.

PMID- 24941120
TI  - Merging national forest and national forest health inventories to obtain an
      integrated forest resource inventory--experiences from Bavaria, Slovenia and
      Sweden.
AB  - BACKGROUNDS, MATERIAL AND METHODS: To meet the demands of sustainable forest
      management and international commitments, European nations have designed a
      variety of forest-monitoring systems for specific needs. While the majority of
      countries are committed to independent, single-purpose inventorying, a minority
      of countries have merged their single-purpose forest inventory systems into
      integrated forest resource inventories. The statistical efficiencies of the
      Bavarian, Slovene and Swedish integrated forest resource inventory designs are
      investigated with the various statistical parameters of the variables of growing
      stock volume, shares of damaged trees, and deadwood volume. The parameters are
      derived by using the estimators for the given inventory designs. The required
      sample sizes are derived via the general formula for non-stratified independent
      samples and via statistical power analyses. The cost effectiveness of the designs
      is compared via two simple cost effectiveness ratios. RESULTS: In terms of
      precision, the most illustrative parameters of the variables are relative
      standard errors; their values range between 1% and 3% if the variables'
      variations are low (s%<80%) and are higher in the case of higher variations. A
      comparison of the actual and required sample sizes shows that the actual sample
      sizes were deliberately set high to provide precise estimates for the majority of
      variables and strata. In turn, the successive inventories are statistically
      efficient, because they allow detecting the mean changes of variables with powers
      higher than 90%; the highest precision is attained for the changes of growing
      stock volume and the lowest for the changes of the shares of damaged trees. Two
      indicators of cost effectiveness also show that the time input spent for
      measuring one variable decreases with the complexity of inventories. CONCLUSION:
      There is an increasing need for credible information on forest resources to be
      used for decision making and national and international policy making. Such
      information can be cost-efficiently provided through integrated forest resource
      inventories.

PMID- 24941122
TI  - Proton diffusion in the hexafluorophosphoric acid clathrate hydrate.
AB  - The hexafluorophosphoric acid clathrate hydrate is known as a "super-protonic"
      conductor: its proton conductivity is of the order of 0.1 S/cm at ca. room
      temperature. The long-range proton diffusion and the associated mechanism have
      been analyzed with the help of incoherent quasi-elastic neutron scattering (QENS)
      and proton pulsed-field-gradient nuclear magnetic resonance ((1)H PFG-NMR). The
      system crystallizes into the so-called type I clathrate structure (SI) at low
      temperature and into the type VII structure (SVII) above ca. 230 K with a melting
      point close to room temperature. While, in the SI phase, no long-range proton
      diffusion is observed (at least faster than the present measurement capabilities,
      i.e., 10(-7) cm(2).s(-1)) with respect to the probed time scale, both techniques
      evidence a long-range proton diffusion process in the SVII phase (3.85 * 10(-6)
      cm(2).s(-1) at 275 K with an activation energy of 0.19 +/- 0.04 eV). QENS
      experiments lead to modeling the microscopic mechanism of the long-range proton
      diffusion by means of a Chudley-Elliot jump diffusion model with a characteristic
      jump distance of 2.79 +/- 0.17 A. In other words, the long-range diffusion occurs
      through a Grotthus mechanism with proton jumping from one water-oxygen site to
      another. Moreover, the analysis of the proton diffusion for hydration numbers
      greater than 6 (i.e., in the SVII structure) reveals that the additional water
      molecules coexisting with the SVII structure act as a "structural defect" barrier
      for the proton diffusivity, responsible for the conductivity. 

PMID- 24941118
TI  - Serum and tissue zinc in epithelial malignancies: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Current studies give us inconsistent results regarding
      the association of neoplasms and zinc(II) serum and tissues concentrations. The
      results of to-date studies using meta-analysis are summarized in this paper.
      METHODS: Web of Science (Science citation index expanded), PubMed (Medline),
      Embase and CENTRAL were searched. Articles were reviewed by two evaluators;
      quality was assessed by Newcastle-Ottawa scale; meta-analysis was performed
      including meta-regression and publication bias analysis. RESULTS: Analysis was
      performed on 114 case control, cohort and cross-sectional studies of 22737
      participants. Decreased serum zinc level was found in patients with lung (effect
      size = -1.04), head and neck (effect size = -1.43), breast (effect size = -0.93),
      liver (effect size = -2.29), stomach (effect size = -1.59), and prostate (effect
      size = -1.36) cancers; elevation was not proven in any tumor. More specific zinc
      patterns are evident at tissue level, showing increase in breast cancer tissue
      (effect size = 1.80) and decrease in prostatic (effect size = -3.90), liver
      (effect size = -8.26), lung (effect size = -3.12), and thyroid cancer (effect
      size = -2.84). The rest of the included tumors brought ambiguous results, both in
      serum and tissue zinc levels across the studies. The association between zinc
      level and stage or grade of tumor has not been revealed by meta-regression.
      CONCLUSION: This study provides evidence on cancer-specific tissue zinc level
      alteration. Although serum zinc decrease was associated with most tumors
      mentioned herein, further--prospective--studies are needed.

PMID- 24941123
TI  - Associations of physical exercise as a lifestyle habit with lean and fat body
      mass and handgrip strength and age in Asian men.
AB  - BACKGROUND: We evaluated how the intensity of physical exercise as a lifestyle
      habit is associated with age, body composition and handgrip strength. METHODS:
      Total body composition was analyzed using DEXA. Exercise scores were derived from
      an administered questionnaire and the scoring was calculated using the Metabolic
      Equivalent of Task (MET). Handgrip strength was measured using a dynamometer.
      RESULTS: Age, independent of exercise intensity, was associated with declining
      lean mass, and handgrip strength and with increasing total body fat. A regular
      physical exercise regime of intensity greater than 1230 MET-min/week was
      associated with higher total lean mass and lean mass in the limbs, and handgrip
      strength and lower fat mass in the limbs. DISCUSSION: We have shown that age was
      associated with lower lean mass especially in the limbs and handgrip strength and
      higher total fat mass. Regular physical exercise as a lifestyle habit of any type
      and of sufficient intensity could help improve muscle strength in the limbs.

PMID- 24941119
TI  - AEG-1 promotes anoikis resistance and orientation chemotaxis in hepatocellular
      carcinoma cells.
AB  - Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC).
      Anoikis resistance and orientation chemotaxis are two important and sequential
      events in tumor cell metastasis. The process of tumor metastasis is known to be
      regulated by AEG-1, an important oncogene that plays a critical role in tumor
      metastasis, though the effects of this oncogene on anoikis resistance and
      orientation chemotaxis in HCC cells are currently unknown. To directly assess the
      role of AEG-1 in these processes, we up-regulated AEG-1 expression via exogenous
      transfection in SMMC-7721 cells, which express low endogenous levels of AEG-1;
      and down-regulated AEG-1 expression via siRNA-mediated knockdown in MHCC-97H and
      HCC-LM3 cells, which express high endogenous levels of AEG-1. Our data directly
      demonstrate that AEG-1 promotes cell growth as assessed by cell
      proliferation/viability and cell cycle analysis. Furthermore, the prevention of
      anoikis by AEG-1 correlates with decreased activation of caspase-3. AEG-1
      dependent anoikis resistance is activated via the PI3K/Akt pathway and is
      characterized by the regulation of Bcl-2 and Bad. The PI3K inhibitor LY294002
      reverses the AEG-1 dependent effects on Akt phosphorylation, Bcl-2 expression and
      anoikis resistance. AEG-1 also promotes orientation chemotaxis of suspension
      cultured cells towards supernatant from Human Pulmonary Microvascular Endothelial
      Cells (HPMECs). Our results show that AEG-1 activates the expression of the
      metastasis-associated chemokine receptor CXCR4, and that its ligand, CXCL12, is
      secreted by HPMECs. Furthermore, the CXCR4 antoagonist AMD3100 decreases AEG-1
      induced orientation chemotaxis. These results define a pathway by which AEG-1
      regulates anoikis resistance and orientation chemotaxis during HCC cell
      metastasis. 

PMID- 24941124
TI  - HCV RNA assay sensitivity impacts the management of patients treated with direct
      acting antivirals.
AB  - BACKGROUND: Application of response-guided therapy (RGT) rules to the treatment
      of HCV infection with pegylated interferon-alpha2a and ribavirin, and direct
      acting antivirals (DAAs) such as the NS3/4A protease inhibitors (PIs) boceprevir
      and telaprevir, relies on the determination of viral genotype and on-treatment
      HCV RNA level. Currently there are few data available regarding the clinical
      impact of the analytical differences that exist between different HCV RNA
      quantification assays on treatment decisions such as those involved in RGT.
      METHODS: We sought to ascertain the concordance between two HCV RNA
      quantification assays, the Roche/High-Pure-System COBAS((r)) TaqMan (CTM) version
      2 and Abbott RealTime HCV (ART), and to understand the impact of different assay
      characteristics on treatment decisions. We evaluated 1,336 specimens collected
      from 74 patients enrolled in the Phase II CHAMPION-2 study of the investigational
      DAAs ABT-450 (an acylsulfonamide NS3/4A PI), ABT-072 and ABT-333 (both non
      nucleoside NS5B polymerase inhibitors). RESULTS: HCV RNA level results were
      highly correlated, but CTM values were higher than those from ART by an average
      of 0.46 log IU/ml. Use of ART HCV RNA level results led to a higher positive
      predictive value of week 4 viral load for the achievement of a sustained
      virological response 24 weeks after the end of treatment (100% versus 87% using
      the lower limit of detection as the threshold). CONCLUSIONS: This study suggests
      that HCV viral load assay performance characteristics need to be taken into
      consideration when managing HCV patients with RGT. Further studies are required
      to determine whether a consensus HCV RNA level threshold can be established or
      whether HCV viral load assays with greater sensitivity can increase cure rates
      with RGT.

PMID- 24941125
TI  - Particle-assisted semidirect breath figure method: a facile way to endow the
      honeycomb-structured petri dish with molecular recognition capability.
AB  - Recently, we have developed a semidirect breath figure (sDBF) method for direct
      fabrication of large-area and ordered honeycomb structures on commercial
      polystyrene (PS) Petri dishes without the use of an external polymer solution. In
      this work, we showed that both the pore size and the pore uniformity of the
      breath figure patterns were controllable by solvent amount. The cross-sectional
      image shows that only one layer of pores was formed on the BF figure patterns. By
      combing the sDBF method and Pickering emulsion and using the modular building
      blocks, we endowed the honeycomb-structured Petri dish with molecular recognition
      capability via the decoration of molecularly imprinted polymer (MIP)
      nanoparticles into the honeycomb pores. The radioligand binding experiments show
      that the MIP nanoparticles on the resultant honeycomb structures maintained high
      molecular binding selectivity. The reusability study indicates that MIP-BF
      patterns had excellent mechanical stability during the radioligand binding
      process. We believe that the modular approach demonstrated in this work will open
      up further opportunities for honeycomb structure-based chemical sensors for drug
      analysis, substrates for catalysts, and scaffold for cell growth. 

PMID- 24941126
TI  - Effect of alkyl side chain location and cyclicity on the aerobic
      biotransformation of naphthenic acids.
AB  - Aerobic biodegradation of naphthenic acids is of importance to the oil industry
      for the long-term management and environmental impact of process water and
      wastewater. The effect of structure, particularly the location of the alkyl side
      chain as well as cyclicity, on the aerobic biotransformation of 10 model
      naphthenic acids (NAs) was investigated. Using an aerobic, mixed culture,
      enriched with a commercial NA mixture (NA sodium salt; TCI Chemicals), batch
      biotransformation assays were conducted with individual model NAs, including
      eight 8-carbon isomers. It was shown that NAs with a quaternary carbon at the
      alpha- or beta-position or a tertiary carbon at the beta- and/or beta'-position
      are recalcitrant or have limited biodegradability. In addition, branched NAs
      exhibited lag periods and lower degradation rates than nonbranched or simple
      cyclic NAs. Two NA isomers used in a closed bottle, aerobic biodegradation assay
      were mineralized, while 21 and 35% of the parent compound carbon was incorporated
      into the biomass. The NA biodegradation probability estimated by two widely used
      models (BIOWIN 2 and 6) and a recently developed model (OCHEM) was compared to
      the biodegradability of the 10 model NAs tested in this study as well as other
      related NAs. The biodegradation probability estimated by the OCHEM model agreed
      best with the experimental data and was best correlated with the measured NA
      biodegradation rate. 

PMID- 24941127
TI  - Variable characteristics of bacteriocin-producing Streptococcus salivarius
      strains isolated from Malaysian subjects.
AB  - BACKGROUND: Salivaricins are bacteriocins produced by Streptococcus salivarius,
      some strains of which can have significant probiotic effects. S. salivarius
      strains were isolated from Malaysian subjects showing variable antimicrobial
      activity, metabolic profile, antibiotic susceptibility and lantibiotic
      production. METHODOLOGY/PRINCIPAL FINDINGS: In this study we report new S.
      salivarius strains isolated from Malaysian subjects with potential as probiotics.
      Safety assessment of these strains included their antibiotic susceptibility and
      metabolic profiles. Genome sequencing using Illumina's MiSeq system was performed
      for both strains NU10 and YU10 and demonstrating the absence of any known
      streptococcal virulence determinants indicating that these strains are safe for
      subsequent use as probiotics. Strain NU10 was found to harbour genes encoding
      salivaricins A and 9 while strain YU10 was shown to harbour genes encoding
      salivaricins A3, G32, streptin and slnA1 lantibiotic-like protein. Strain GT2 was
      shown to harbour genes encoding a large non-lantibiotic bacteriocin (salivaricin
      MPS). A new medium for maximum biomass production buffered with 2-(N
      morpholino)ethanesulfonic acid (MES) was developed and showed better biomass
      accumulation compared with other commercial media. Furthermore, we extracted and
      purified salivaricin 9 (by strain NU10) and salivaricin G32 (by strain YU10) from
      S. salivarius cells grown aerobically in this medium. In addition to bacteriocin
      production, S. salivarius strains produced levan-sucrase which was detected by a
      specific ESI-LC-MS/MS method which indicates additional health benefits from the
      developed strains. CONCLUSION: The current study established the bacteriocin,
      levan-sucrase production and basic safety features of S. salivarius strains
      isolated from healthy Malaysian subjects demonstrating their potential for use as
      probiotics. A new bacteriocin-production medium was developed with potential
      scale up application for pharmaceuticals and probiotics from S. salivarius
      generating different lantibiotics. This is relevant for the clinical management
      of oral cavity and upper respiratory tract in the human population.

PMID- 24941129
TI  - Design, synthesis and antiproliferative activity of functionalized flavone
      triazole-tetrahydropyran conjugates against human cancer cell lines.
AB  - Under optimized reaction conditions, an efficient synthetic method has been
      developed to afford the functionalized flavone-triazole-tetrahydropyran
      conjugates via click reactions. The Cu-catalyzed 1,3-dipolar cycloaddition
      reaction gave the pure products, 5-iodo- and 5-H-1-(tetrahydropyran)-1,2,3
      triazol-4-(3-methoxylflavone) derivatives in excellent yield (90-98%) within 1-3
      h. Further, Pd-catalyzed Suzuki coupling of 5-iodo-1,2,3-triazoles with
      phenylboronic acids afforded 5-phenyl-1-(tetrahydropyran)-1,2,3-triazol-4-(3
      methoxylflavone) derivatives in excellent yield (93-95%) in 4-5 h. Products (3a
      l, 4a-j) were screened in vitro for their anti-proliferative activity against
      three human cancer cell lines (MDA-MB 231, KCL22 and Hela). Compounds 3c, 3g, 3i,
      3j, 4c and 4h have shown better cytotoxicity (IC50 0.61-1.68 MUM) than the
      reference drugs. Compounds 4e (IC50 0.70 MUM), 3j (IC50 0.61 MUM) and 4d (IC50
      0.65 MUM) exhibited anti-proliferative activity better than the reference drugs
      against the MDA-MB 231 cells, KCL22 cells and HeLa cells respectively.

PMID- 24941128
TI  - Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives.
AB  - A series of 7-hydroxycoumarin derivatives connected by an amidic linker to the
      different amines were designed and synthesized as cholinesterase inhibitors. Most
      compounds showed remarkable inhibitory activity against acetylcholinesterase
      (AChE) and butyrylcholinesterase (BuChE). Among them, N-(1-benzylpiperidin-4
      yl)acetamide derivative 4r with IC50 value of 1.6 MUM was the most potent
      compound against AChE. The selectivity index of compound 4r for anti-AChE
      activity was about 26. Moreover, the compound 4r significantly protected PC12
      neurons against H2O2-induced cell death at low concentrations. The docking study
      of compound 4r with AChE enzyme showed that both CAS and PAS are occupied by the
      ligand.

PMID- 24941130
TI  - Synthesis, antimicrobial and cytotoxic activities, and structure-activity
      relationships of gypsogenin derivatives against human cancer cells.
AB  - A series of gypsogenin (1) derivatives (1a-i) was synthesized in good yields, and
      the derivatives' structures were established using UV, IR, (1)H NMR, (13)C NMR,
      and LCMS spectroscopic data. Among the tested compounds, 1a, 1b, 1d, 1e, and
      gypsogenin (1) showed antimicrobial activities against Bacillus subtilis and
      Bacillus thrungiensis, with inhibition zones of 10-14 mm. In addition, compounds
      1b, 1d, and 1e showed antimicrobial activities against Bacillus cereus, with
      inhibition zones of 9-14 mm. Using six human cancer cell lines in vitro, the
      cytotoxic activities of all tested compounds were determined by calculating the
      IC50 values. Doxorubicin and paclitaxel were used as controls. Among the tested
      compounds, 1a, 1c, and 1d had inhibitory effects with IC50 values of 3.9 MUM (HL
      60 cells), 5.15 MUM (MCF-7 cells), and 5.978 MUM (HL-60), respectively. To
      determine the type of cell death, Hoechst 33258 (HO) and propidium iodide (PI)
      double staining was used. Especially, gypsogenin (1) and compound 1a triggered
      the apoptotic mechanism at a concentration of 20 MUM. Thus, gypsogenin (1) and
      compounds 1a, 1c, and 1d possess varying degrees of biological activities and can
      be considered as potential antitumor agents.

PMID- 24941132
TI  - Differentiation of manuka honey from kanuka honey and from jelly bush honey using
      HS-SPME-GC/MS and UHPLC-PDA-MS/MS.
AB  - In the present study, pollen-identical pure manuka and kanuka honeys and an
      Australian jelly bush honey were analyzed for the nonvolatiles by UHPLC-PDA-MS/MS
      and for the volatiles by HS-SPME-GC/MS. A chromatographic profile matchup by
      means of characteristic marker compounds achieved a clear discrimination between
      manuka, kanuka, and jelly bush honey. UHPLC-PDA profiles of manuka honey show
      leptosin, acetyl-2-hydroxy-4-(2-methoxyphenyl)-4-oxobutanate, 3-hydroxy-1-(2
      methoxyphenyl)-penta-1,4-dione, kojic acid, 5-methyl-3-furancarboxylic acid, and
      two unknown compounds as prominent, kanuka honey was characterized by 4
      methoxyphenyllactic acid, methyl syringate, p-anisic acid, and lumichrome. 2
      Methylbenzofuran, 2'-hydroxyacetophenone, and 2'-methoxyacetophenone were markant
      volatiles for manuka honey, whereas kanuka honey was characterized by 2,6,6
      trimethyl-2-cyclohexene-1,4-dione, phenethyl alcohol, p-anisaldehyde, and an
      unknown compound in HS-SPME-GC/MS. The jelly bush honey differed from the manuka
      honey by higher contents of 2-methoxybenzoic acid and an individual unknown
      substance in the PDA profile and by lower intensities of 2'-methoxyacetophenone,
      higher concentrations of cis-linalool oxide, and 3,4,5-trimethylphenol in the HS
      SPME-GC/MS profile. 

PMID- 24941131
TI  - Comparison of patients from Nigeria and the USA highlights modifiable risk
      factors for sickle cell anemia complications.
AB  - To identify factors that affect manifestations of sickle cell anemia we compared
      patients 11-30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n =
      214) and University of Illinois at Chicago, Chicago, IL, USA (n = 209).
      Paralleling findings in the general populations of the two countries, the Chicago
      patients were more often overweight or obese as defined by the Centers for
      Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had
      elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood
      Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not
      receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the
      Chicago patients. Consistent with lower rates of elevated BP and increased body
      mass index (BMI), stroke history was less frequent in the Ibadan patients >=18
      years old. Furthermore, in combined analyses, systolic and diastolic BP directly
      correlated with BMI, and elevated weight status independently associated with
      history of stroke. Our findings are consistent with the possibility that higher
      values for BMI and BP in Chicago sickle cell anemia patients may contribute to an
      increased risk of stroke and highlights the need for measures to reduce these
      risk factors. On the other hand, lower pneumococcal vaccination and HU therapy
      rates in Ibadan patients highlights the need for more improved vaccination
      coverage and for studies to define the role of HU therapy in Africa.

PMID- 24941133
TI  - Comment on "computational study on the vinyl azide decomposition".

PMID- 24941134
TI  - Sodium channel antagonists for the treatment of migraine.
AB  - INTRODUCTION: Migraine has a strong social impact, influencing both quality of
      life and work productivity. Therapeutic approach of migraine consists of a
      multimodal program of pharmacotherapy and behavioral therapy in order to reduce
      the risk of chronification. Indications for the use of preventive therapy are
      three or more attacks per month, significant disability, attack duration that is
      > 90 min. AREAS COVERED: In this review, studies conducted on sodium channel
      antagonists for the prophylaxis of migraine are selected using the International
      Classification of Headache Disorders (ICHD)-I and -II diagnostic criteria for
      migraine and are open-label and placebo-controlled studies. EXPERT OPINION:
      Several sodium channel antagonists, such as valproic acid, topiramate,
      lamotrigine, zonisamide, carbamazepine and oxcarbazepine, are widely used in
      migraine although without similar level of efficacy. Among these antiepileptic
      drugs, valproic acid and topiramate seem to be more effective in migraine, as
      reported in the majority of controlled studies. In spite of their high efficacy
      rate, important side effects should be always monitored, especially depression,
      cognitive functions, weight gain, sleepiness and dizziness. The usefulness of
      this class drug will be dramatically improved by using ongoing data on individual
      pharmacogenomics profile.

PMID- 24941135
TI  - Predictors of oral health-related quality of life in patients following stroke.
AB  - Objectives: To explore the influence of socio-demographic and clinical oral
      health factors on oral health-related quality of life (OHRQoL) in patients after
      stroke, and to monitor OHRQoL outcomes following the provision of an in-hospital
      oral health intervention programme. Design: OHRQoL was measured before and after
      randomization and provision of oral health promotion interventions in a
      prospective clinical trial. Subjects: Eighty-one patients admitted to a stroke
      rehabilitation ward. Methods: OHRQoL was assessed using the Oral Health Impact
      Profile-14 (OHIP-14) and Oral Health Transition Scale upon admission and 3 weeks
      later following provision of an oral health promotion programme. Potential
      factors were examined for their association with OHRQoL outcomes. Results: Lack
      of a regular daily brushing habit was significantly associated with 6 of 8
      transition scale items (p < 0.01) at baseline, while significant improvements in
      OHRQoL were observed over the course of the clinical trial for all patients as a
      whole (p < 0.05). Conclusion: OHRQoL is compromised following stroke and may be
      influenced by the lack of a regular daily brushing habit during hospitalization.
      The early re-establishment of an oral hygiene protocol is a priority in stroke
      rehabilitation wards in order to improve clinical oral health and OHRQoL.

PMID- 24941136
TI  - Neural correlates of emotion regulation in patients with schizophrenia and non
      affected siblings.
AB  - BACKGROUND: Patients with schizophrenia often experience problems regulating
      their emotions. Non-affected relatives show similar difficulties, although to a
      lesser extent, and the neural basis of such difficulties remains to be
      elucidated. In the current paper we investigated whether schizophrenia patients,
      non-affected siblings and healthy controls (HC) exhibit differences in brain
      activation during emotion regulation. METHODS: All subjects (n = 20 per group)
      performed an emotion regulation task while they were in an fMRI scanner. The task
      contained two experimental conditions for the down-regulation of emotions
      (reappraise and suppress), in which IAPS pictures were used to generate a
      negative affect. We also assessed whether the groups differed in emotion
      regulation strategies used in daily life by means of the emotion regulation
      questionnaire (ERQ). RESULTS: Though the overall negative affect was higher for
      patients as well as for siblings compared to HC for all conditions, all groups
      reported decreased negative affect after both regulation conditions. Nonetheless,
      neuroimaging results showed hypoactivation relative to HC in VLPFC, insula,
      middle temporal gyrus, caudate and thalamus for patients when reappraising
      negative pictures. In siblings, the same pattern was evident as in patients, but
      only in cortical areas. CONCLUSIONS: Given that all groups performed similarly on
      the emotion regulation task, but differed in overall negative affect ratings and
      brain activation, our findings suggest reduced levels of emotion regulation
      processing in neural circuits in patients with schizophrenia. Notably, this also
      holds for siblings, albeit to a lesser extent, indicating that it may be part and
      parcel of a vulnerability for psychosis.

PMID- 24941137
TI  - Hydroxyl-directed stereoselective diboration of alkenes.
AB  - An alkoxide-catalyzed directed diboration of alkenyl alcohols is described. This
      reaction occurs in a stereoselective fashion and is demonstrated with cyclic and
      acyclic homoallylic and bishomoallylic alcohol substrates. After oxidation, the
      reaction generates 1,2-diols such that the process represents a method for the
      stereoselective directed dihydroxylation of alkenes. 

PMID- 24941139
TI  - Editorial.

PMID- 24941140
TI  - Sexual dysfunction in female patients with panic disorder alone or with
      accompanying depression.
AB  - Objective. The aim of this study was to evaluate sexual dysfunction in female
      patients with panic disorder and to investigate the impact of accompanying
      depression with regard to sexual dysfunction. Method. Twelve patients who met the
      diagnostic criteria for panic disorder without depression (P) and 28 patients who
      met the diagnostic criteria for panic disorder with depression (PD) were compared
      to 13 control cases (C). Arizona Sexual Experience Scale (ASEX) was used to
      measure sexual experience. Results. ASEX scores were significantly different
      between the three groups (P=0.001). In two group comparisons sexual desire and
      aversion subscores of ASEX were significantly decreased in group PD when compared
      with groups P and C (P=0.01). Also, our results show that the difference of
      orgasmic experience subscore of ASEX in groups PD and C was found to be
      statistically significant (P=0.01). On the other hand, there was no statistical
      difference between P and PD groups in terms of orgasmic experience (P=0.16).
      Conclusion. These results suggest that decreased sexual desire and high sexual
      aversion may be presenting symptoms of depression in patients with panic
      disorder. If there is no depression, patients with panic disorder should be
      questioned especially for orgasmic problems. 

PMID- 24941141
TI  - Study of impulse control disorders among women presenting nicotine dependence.
AB  - Objective. Impulse control disorders (ICDs) include intermittent explosive
      disorder, kleptomania, trichotillomania, pyromania and pathological gambling.
      Several studies have showed an association between ICDs and alcohol use
      disorders. The rate of co-occurrence ICDs and nicotine dependence has never been
      investigated. We thus assessed the frequency of all ICDs in a population of
      nicotine-dependent women compared to non-smoking women. We also checked criteria
      of two other impulsive behaviours, compulsive buying and bulimia. Methods. Five
      hundred consecutive patients were assessed by a general practitioner in Paris
      (France). One hundred and twenty-seven women presenting the DSM-IV-R criteria for
      nicotine dependence were included. They were compared to 127 women consulting the
      same practitioner but who did not smoke. Diagnosis of ICD (pyromania,
      kleptomania, trichotillomania, intermittent explosive disorder, pathological
      gambling) and of bulimia was based on DSM-IV criteria and a modified version of
      the Minnesota Impulsive Disorders Interview (MIDI). Diagnosis of compulsive
      buying was made with the McElroy et al. criteria and a specific questionnaire.
      Cigarette smoking was studied using the Fagerstrom questionnaire and the DSM-IV-R
      criteria for nicotine dependence. Alcohol use disorders were assessed with the
      DSM-IV-R criteria for dependence and the CAGE and the MAST questionnaires.
      Results. Thirteen patients presented trichotillomania, 22 explosive intermittent
      disorder and 12 pathological gambling. All these diagnoses were equally frequent
      in the nicotine-positive and nicotine-negative groups. We found no case of
      pyromania. Compulsive buying was the most frequent impulse control disorder. It
      was significantly more frequent in the nicotine-positive group than in the
      nicotine-negative group (58 vs. 39 cases, P=0.01). Scores of the compulsive
      buying scale were higher in the nicotine-positive group (4.07 vs. 2.9, P=0.01).
      None of the patients presented an association of two or more ICDs. Patients from
      the nicotine-positive group drunk higher quantities of alcohol each day, consumed
      alcohol more frequently each week and were more often intoxicated each week with
      alcohol. Their mean MAST scores of alcohol abuse disorders were higher.
      Conclusion. A total of 45.6% of the nicotine-dependent women presented compulsive
      buying and 23.6% bulimia. Compulsive buying was significantly more frequent among
      nicotine-dependent subjects than controls. Other impulse control disorders were
      as frequent among nicotine-dependent women as in controls. A total of 8.6%
      presented explosive intermittent disorder, 4.7% pathological gambling and 5%
      trichotillomania. Nicotine dependence in women was also associated with a higher
      level of alcohol consumption. These results indicate the possible need to
      systematically screen nicotine-dependent women, regardless of their motivation
      for consultation, for alcohol dependence, bulimia and compulsive buying. 

PMID- 24941138
TI  - Cimicifuga racemosa extract for relieving menopausal symptoms: a randomized
      controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of black cohosh extract 40 mg/day for
      relieving moderate to severe menopausal symptoms and improving quality of life in
      Thai women. METHODS: A randomized, double-blind, placebo-controlled clinical
      trial was conducted in a menopause clinic of a tertiary-care university hospital
      during 2011-2013. Participants were peri- or postmenopausal Thai women aged at
      least 40 years, who have moderate to severe menopausal symptoms evaluated using
      the Kupperman index (KI). Outcome measures included KI, frequency of hot flushes,
      Menopause-Specific Quality of Life (MENQOL) score, participants' global
      satisfaction and safety outcomes. RESULTS: There were 54 participants assigned to
      treatment (black cohosh extract 40 mg/day, n = 27) or placebo group (n = 27).
      Both the treatment and placebo groups had comparable baseline KI scores (33.9 +/-
      7.9 vs. 31.3 +/- 6.8), frequency of hot flushes (3.1 +/- 2.0 vs. 2.8 +/- 2.1),
      and MENQOL scores, all of which improved with time. Neither the improvements nor
      the global satisfaction were significantly different between the two groups; but
      the proportion of participants with moderate to severe symptoms seemed to be
      lower in the treatment group than in the placebo group (40% vs. 60%, p = 0.174).
      There was no serious adverse event or significant change in liver function tests.
      CONCLUSIONS: A black cohosh extract of 40 mg/day is not superior to a placebo for
      relieving moderate to severe menopausal symptoms or improving quality-of-life
      scores in Thai women.

PMID- 24941142
TI  - Coercion in psychiatric care: clinical, legal, and ethical controversies.
AB  - Despite a long-standing tradition of the use of coercion in psychiatric care,
      such as involuntary admission and treatment, few have systematically addressed
      this issue. In recent years, more research has been carried out, suggesting that
      the use of coercion has important and complex legal, ethical, and clinical
      implications. In the present article, types and rates of coercion are presented
      and central topics including competency, ethics, and the reasons given for the
      use of coercion, are critically discussed. 

PMID- 24941143
TI  - Naturalistic study on ICD-10 personality disorders.
AB  - Objective. To study the frequency, socio-demography and comorbidity of ICD-10
      personality disorders (PD), especially of emotionally unstable PD, in psychiatric
      inpatients. To test the subdivision of emotionally unstable PD in impulsive and
      borderline subtypes. Methods. Data on all psychiatric hospital stays in the
      Canton of Zurich in the years 1998-2002, routinely collected at the time of each
      patient's hospitalization, were analysed. Results. PD was diagnosed in 10.2% of
      all inpatients, and the proportion of emotionally unstable PD diagnosis was
      54.5%. There are considerable differences between impulsive and borderline
      personality disorders with respect to sex, age, employment status and
      comorbidity. Conclusion. Emotionally unstable PD is the most frequent PD in
      clinical settings. Its differentiation into impulsive and borderline subtypes is
      justified. 

PMID- 24941144
TI  - Polypharmacy in schizophrenia.
AB  - In contrast to research studies that limit the use of concomitant psychotropic
      medications in the treatment of schizophrenia, polypharmacy is common in real
      world, clinical practice. The use of psychotropic medications as an adjunct to
      antipsychotic agents is often necessitated by the poor response to monotherapy
      with one antipsychotic agent. This paper discusses the prevalence of polypharmacy
      in clinical settings, reviews the evidence for the adjunctive use of
      antipsychotics, anticonvulsants, lithium, antidepressants, benzodiazepines and
      other psychotropics in the treatment of schizophrenia, and offers suggestions
      toward use of polypharmacy in difficult and practical clinical settings. 

PMID- 24941145
TI  - Prolonged duration of untreated psychosis in nonaffective first-episode psychotic
      disorders compared to other psychoses.
AB  - Introduction. While the consequences of the duration of untreated psychosis (DUP)
      represent an active area of research, less attention has been focused on the
      determinants of the DUP. This analysis assessed several potential determinants of
      the DUP from a practice-based survey. Method. Data on selected patients in their
      first treatment episode for psychotic symptoms were obtained from 104 practicing
      physicians. Patients with a long DUP (n=31), defined as >4 weeks, were compared
      to patients with a short DUP (<=4 weeks, n=28). Results. The long-DUP group had a
      higher percentage of patients with nonaffective psychotic disorders (58%)
      compared to the short-DUP group (29%). The median DUP among those with
      nonaffective psychotic disorders was 8 weeks, compared to 3 weeks among those
      with other psychotic disorders. The long-DUP group had a higher percentage of
      patients rated as uncertain about or denying a mental illness (55% compared to
      25% in the short-DUP group). The presence of negative symptoms approached
      significance in terms of differentiating between the two groups, with 66% of the
      long-DUP group having negative symptoms compared to 39% of the short-DUP group.
      When three variables (nonaffective psychotic disorder versus other psychoses,
      insight, and negative symptoms) were entered into a logistic regression model,
      only diagnostic category remained an independently significant predictor.
      Conclusion. In this practice-based sample, patients with nonaffective psychotic
      disorders were more likely to have a longer DUP than patients who developed
      psychotic symptoms in the context of mood disorders, substance use disorders, or
      other disorders. 

PMID- 24941146
TI  - A case series on the development of rest-activity rhythm and quality of sleep in
      patients hospitalized for treatment of uni- or bipolar depression: a potential
      role for quetiapine.
AB  - Objectives. To assess the development of the rest-activity rhythm and quality of
      sleep during course of treatment of patients with major depressive episode
      receiving antidepressant treatment plus quetiapine. Methods. Ten patients with
      major depressive episode were followed over 4 weeks. Motor activity was measured
      with actigraphy, sleep with the Pittsburgh Sleep Quality Index (PSQI), and
      depression was followed with HAM-D-21 and BDI. Correlations and associations were
      calculated with non-parametric statistical tests. Results. Circadian motor
      activity improved during the 4 weeks treatment period only for daytime-related
      motor activity (M10), but not for night-time-related motor activity (L5).
      Patients with statistically significant higher sleep efficiency scores and sleep
      fraction on the actigraph after week 1 showed clinical improvement on the HAM-D
      score after week 4. Patients with good sleep efficiency at week 1 (assessed by
      PSQI) showed statistically significant clinical improvement of depression after
      week 4. Conclusions. Various sleep parameters at week 1 of treatment seem to be
      predictive for treatment outcome of depression after week 4. Actigraphy and
      subjective sleep assessment with PSQI are useful tools to predict treatment
      outcome of depression. The positive effects of quetiapine on motor activity and
      sleep show the clinical significance of our findings. 

PMID- 24941147
TI  - Symptom control, functioning, and hospitalization status in French patients
      changed from oral atypical antipsychotics to risperidone long-acting injectable.
AB  - Objective. To investigate efficacy and tolerability of risperidone long-acting
      injectable (RLAI) in French patients with schizophrenia or other psychotic
      disorders, who were all switching from previous treatment with oral atypical
      antipsychotics. The impact of treatment with RLAI on the hospitalization status
      of these patients was also examined. Methods. Clinically stable patients
      requiring a treatment change received 25 mg RLAI (increased to 37.5 or 50 mg if
      required) every 2 weeks for 6 months. Results. Of 130 patients (68.5% male, mean
      age 36.2 years), most (83.8%) had DSM-IV schizophrenia (mainly paranoid).
      Previous treatments were risperidone (80.8%), olanzapine (10.0%) and amisulpride
      (10.0%). Out of 66 patients hospitalized at baseline, 51 were outpatients at
      endpoint. Mean total PANSS, CGI-S and GAF scores were significantly reduced from
      baseline to treatment endpoint (p<0.001). Of those patients reported as moderate
      to severely ill at the beginning of the trial (81.3%), fewer had the same
      classification at endpoint (50.8%). Mean scores for total ESRS and Parkinsonism
      subscales were significantly reduced after only 1 month of treatment (p<0.001).
      Conclusion. Treatment with RLAI significantly improved disease symptoms,
      functioning, hospitalization status, and reduced movement disorders, in psychotic
      patients considered clinically stable on oral atypical antipsychotics. 

PMID- 24941148
TI  - Pharmacological treatment of hospitalised schizophrenic patients in Belgium.
AB  - Objective. The aim of the present study is two-fold: (1) evaluate to what degree
      antipsychotic prescribing patterns are in accordance with published treatment
      recommendations; (2) gain insight in factors determining guideline adherence or
      non-adherence. Method. The medication use at first assessment of 1215 psychotic
      in-patients, participating in a naturalistic prospective follow-up study, was
      registered. Results. In Belgium, use of novel antipsychotics is frequent (69.4%)
      in hospitalised schizophrenic patients. In the total sample 57.8% receive only
      one antipsychotic drug. The majority of patients are treated with drugs of only
      one antipsychotic drug group, either first-generation antipsychotics (FGA)
      (27.8%) or second-generation antipsychotics (SGA) (42.3%). Roughly one-quarter of
      patients combine different types of antipsychotic. Antipsychotic dosing is
      adequate for the majority of patients, but one-third receive a higher than
      recommended dose. The use of SGA is influenced by the patients' age and duration
      of illness. Polypharmacy and the administration of high doses FGA are influenced
      by symptom severity and illness duration. No clear determinants of SGA overdosing
      were found. Conclusions. SGA are most frequently used for the treatment for
      schizophrenic psychosis. Polypharmacy and excessive dosing are still frequently
      observed and appear influenced by the patient's clinical condition and illness
      duration. Evidence-based guidelines have not been sufficiently implemented in
      daily clinical practice yet. 

PMID- 24941149
TI  - Comparison of treatment responses and clinical characteristics of early-onset and
      late-onset obsessive-compulsive disorder.
AB  - Objective. The clinical characteristics and response to pharmacotherapy of adult
      patients with early-onset and late-onset obsessive-compulsive disorder (OCD) were
      compared in this study. Methods. A total of 50 outpatients with OCD diagnosed
      according to DSM-IV criteria (early-onset: 20; late-onset: 30) were included in
      the study. After initial clinical evaluation with The Structured Clinical
      Interview for DSM-IV/Clinical Version (SCID-I/CV), The Structured Clinical
      Interview for DSM-III-R Personality Disorders (SCID-II) and Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS), all patients were treated with fluvoxamine, sertraline
      or paroxetine for 12 weeks. Treatment response was defined as a >=35% reduction
      in the Y-BOCS-total scores from baseline in a 12-week follow-up period. Results.
      Forty-three patients (early-onset: 16; late-onset: 27) completed the study. The
      early-onset group had higher frequencies of symmetry/exactness obsessions and
      ordering/arranging compulsions, and the late-onset group had higher mean age at
      assessment. Nine (56.3%) patients with early-onset and 18 (66.7%) with late-onset
      responded to pharmacotherapy. The difference between response rates was not
      statistically significant. Conclusions. Our study suggests that although there
      are some phenomenological differences between patients with early-onset OCD and
      late-onset OCD, these patients have similar responses to pharmacotherapy. 

PMID- 24941150
TI  - Five-year comparison of antidepressant monotherapy.
AB  - Objective. This study compares the effectiveness of several antidepressants in
      maintaining remission in unipolar depressed outpatients. Method. A retrospective
      chart review was performed on 2475 patients being seen in a rural private
      psychiatric practice. The study focused on those patients who had a clinical
      diagnosis of unipolar depression, and who achieved remission on antidepressant
      monotherapy. Data collected included patient demographics, Carroll Depression
      Rating Scale scores, and medication history. Results. A total of 346 patients
      (14%) met the inclusion criteria. Patients achieved remission in an average of
      0.36 years and had an average of 0.28 relapses per year of treatment. Patients on
      escitalopram and sertraline had the shortest time until remission (0.24 and 0.27
      years, respectively) but sertraline patients remained the longest in remission
      (62% after 5 years) and had the lowest percentage of treatment time spent in
      relapse (8%). Conclusions. Sertraline and to a lesser extent paroxetine were
      deemed superior to several other antidepressants in terms of maintaining
      remission and preventing relapse. 

PMID- 24941151
TI  - Discontinuation of citalopram medication and striatal dopamine activity.
AB  - A 35-year-old caucasian woman who suffered from major depression with marked
      psychomotor symptoms was treated with a selective serotonin re-uptake inhibitor
      (SSRI), citalopram. After 16 months successful treatment, the medication was
      gradually discontinued. One week after stopping citalopram, she experienced
      lowered mood and unnatural slowness in her movements. These symptoms were
      associated with low striatal dopamine (DA) activity as measured with baseline and
      follow-up [(18)F]DOPA PET scans. We suggest that stimulation of serotonergic
      system in the brain increases dopaminergic activity in the striatum. After
      cessation of this stimulation, striatal dopaminergic activity may decrease
      considerably in vulnerable patients and cause transient emotional and psychomotor
      discontinuation symptoms that disappear spontaneously in a few weeks. 

PMID- 24941152
TI  - Myotoxicity in acute clozapine overdose.
AB  - Clozapine, an atypical antipsychotic has been associated with several side
      effects like sialorrhoea, sedation, tachycardia, agranulocytosis and seizure.
      Myotoxicity and neurotoxicity have also been reported with long-term use of
      clozapine. We report here a case of myotoxicity developing after acute overdose
      of clozapine. A 17-year-old daughter of a schizophrenic father consumed 3.9 g of
      clozapine in an attempted suicide. Clinical features of myotoxicity were detected
      on the third day, after the patient regained full consciousness. Elevated
      creatinine phosphokinase and muscle biopsy confirmed myositis. The patient also
      had tachycardia, which persisted for 10 days. This combination of myositis
      induced muscle weakness and tachycardia is likely to be associated with poor
      outcome in clozapine overdose. 

PMID- 24941153
TI  - Speaker abstracts.

PMID- 24941154
TI  - Mice in vivo toxicity studies for monohaloacetamides emerging disinfection
      byproducts based on metabolomic methods.
AB  - Haloacetamides (HAcAms) as a new class of nitrogenous disinfection byproducts (N
      DBPs) have been widely detected in drinking water and reclaimed water.
      Cytotoxicity and genotoxicity of monoHAcAms are determined by the leaving
      tendency of the halogens and decrease following a rank order of iodoacetamide
      (IAcAm)>bromoacetamide (BAcAm)?chloroacetamide (CAcAm). However, the in vivo
      toxicity date for monoHAcAms is limited. In this study, hepatic oxidative stress
      and metabolomics responses in mice corresponding to monoHAcAms exposure were
      investigated. Exposure to the monoHAcAms decreased the activities of catalase
      (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the
      levels of malonaldehyde (MDA) and increased the level of 8-hydroxy-2
      deoxyguanosine (8-OHdG), indicating that each exposure generated oxidative stress
      in mice liver. Metabolomic alterations were also induced by each monoHAcAms
      exposure. In addition, disruptions of metabolic pathways, related to amino acid,
      energy and lipid metabolism, were identified based on the significantly changed
      metabolites. These data, for the first time, provide a comprehensive view for the
      toxic effects of monoHAcAms.

PMID- 24941156
TI  - Effect of molecular asymmetry on the charge transport physics of high mobility n
      type molecular semiconductors investigated by scanning Kelvin probe microscopy.
AB  - We have investigated the influence of the symmetry of the side chain substituents
      in high-mobility, solution processable n-type molecular semiconductors on the
      performance of organic field-effect transistors (OFETs). We compare two molecules
      with the same conjugated core, but either symmetric or asymmetric side chain
      substituents, and investigate the transport properties and thin film growth mode
      using scanning Kelvin probe microscopy (SKPM) and atomic force microscopy (AFM).
      We find that asymmetric side chains can induce a favorable two-dimensional growth
      mode with a bilayer structure, which enables ultrathin films with a single
      bilayer to exhibit excellent transport properties, while the symmetric molecules
      adopt an unfavorable three-dimensional growth mode in which transport in the
      first monolayer at the interface is severely hindered by high-resistance grain
      boundaries. 

PMID- 24941157
TI  - Role of SLAM family receptors and specific adapter SAP in innate-like
      lymphocytes.
AB  - Innate-like lymphocytes, which comprise an integral part of the immune system,
      possess unique developmental and functional capabilities that set them apart from
      conventional T and B lymphocytes. Strategically located to act as a first line of
      defense against pathogens, they behave as innate cells. To efficiently perform
      their innate functions, these populations are endowed with common phenotypic
      characteristics that include the expression of semi-invariant TCR or BCR and
      activation/memory cell markers. Moreover, they have the capacity to rapidly
      respond to pathogenic threats and the ability to ignite adaptive immune response
      in synchrony with myeloid cells. Indeed, all of these common features mirror a
      shared molecular program, in which Signaling Lymphocytic Activation Molecule
      Family (SLAMF) receptors and their cytoplasmic binding partner, the adapter
      signaling lymphocytic activation-associated protein (SAP), play a crucial role.
      Despite the extensive characterization of SLAMF molecules as a group of cell
      surface receptors that regulate and interconnect both innate and adaptive immune
      cells, their relevance in innate-like lymphocyte ontogeny and physiology has
      recently taken center stage. Here, we review the current understanding of the
      roles SLAMF receptors and SAP adaptor molecules play in the biology of innate
      like lymphocytes. 

PMID- 24941158
TI  - Mechanism of activation-induced cell death of T cells and regulation of FasL
      expression.
AB  - Activation-induced cell death (AICD) of T cells is a process for regulating the
      peripheral immune system. The fate of a T cell is controlled by numerous signals
      derived from various stimuli, such as antigens, cytokines, and chemokines. In
      healthy humans, overactivated or autoreactive T cells are harmful and are
      eliminated to maintain the immune system. AICD in T cells by Fas/FasL-mediated
      apoptosis is triggered by the switch from life to death through several signaling
      molecules. The control or distribution of Fas or FasL expression largely affects
      AICD of T cells. Although autoimmune diseases are considered to be induced by
      multiple factors, an impaired immune system with AICD by Fas/FasL-mediated
      apoptosis leads to the onset or development of autoimmunity. Based on published
      reports, this review describes the regulatory mechanisms involved in AICD of T
      cells by Fas/ FasL-mediated apoptosis and the associations between AICD and
      autoimmunity in humans and animal models. 

PMID- 24941155
TI  - Functional evolution of ribonuclease inhibitor: insights from birds and reptiles.
AB  - Ribonuclease inhibitor (RI) is a conserved protein of the mammalian cytosol. RI
      binds with high affinity to diverse secretory ribonucleases (RNases) and inhibits
      their enzymatic activity. Although secretory RNases are found in all vertebrates,
      the existence of a non-mammalian RI has been uncertain. Here, we report on the
      identification and characterization of RI homologs from chicken and anole lizard.
      These proteins bind to RNases from multiple species but exhibit much greater
      affinity for their cognate RNases than for mammalian RNases. To reveal the basis
      for this differential affinity, we determined the crystal structure of mouse,
      bovine, and chicken RI.RNase complexes to a resolution of 2.20, 2.21, and 1.92A,
      respectively. A combination of structural, computational, and bioinformatic
      analyses enabled the identification of two residues that appear to contribute to
      the differential affinity for RNases. We also found marked differences in
      oxidative instability between mammalian and non-mammalian RIs, indicating
      evolution toward greater oxygen sensitivity in RIs from mammalian species. Taken
      together, our results illuminate the structural and functional evolution of RI,
      along with its dynamic role in vertebrate biology. 

PMID- 24941159
TI  - Transcriptional regulation of IL-10 and its cell-specific role in vivo.
AB  - IL-10 is an important anti-inflammatory cytokine that plays important roles in
      controlling inflammatory responses and keeping the immune system in check
      following activation. Loss of IL-10 function in mice or humans results in the
      development of inflammatory bowel disease in response to an elevated immune
      response to the gut flora. IL-10 also acts to prevent excessive inflammation
      during the course of infection and has been implicated in a variety of autoimmune
      conditions. In response to inflammatory signals, IL-10 can be produced by a
      number of immune cells including T cells, B cells, macrophages, and dendritic
      cells. Distinct mechanisms control the production of IL-10 in these different
      cells types. In this review, we describe recent studies that have looked at the
      signaling pathways that regulate IL-10 production in these cells. Given the
      number of cell types that produce IL-10, it is perhaps not surprising that the in
      vivo source of IL-10 can vary in different immune models. We also describe how
      work using conditional IL-10 knockout mice or adoptive transfer of IL-10
      deficient cells has begun to further our understanding regarding which specific
      immune cells are required for IL-10 production in vivo under different
      conditions. 

PMID- 24941162
TI  - Antidiabetic potential of polysaccharides from the white oyster culinary
      medicinal mushroom Pleurotus florida (higher Basidiomycetes).
AB  - This study was designed to examine the antihyperglycemic potential of the
      polysaccharide fraction of Pleurotus florida. Hyperglycemia was induced by
      streptozotocin (50 mg/kg intraperitoneal). Single- and multiple-dose studies were
      performed to assess the antihyperglycemic potential of the P. florida
      polysaccharides (PFPs). Organisation for Economic Co-operation and Development
      guideline 423 was followed to study the acute toxicity of PFP. PFP was found to
      be nontoxic up to 4000 mg/kg. In this investigation, 200- and 400-mg/kg doses of
      PFP were used. Blood glucose, serum cholesterol, triglycerides, urine glucose and
      ketones, and glycosylated hemoglobin were estimated, and biological markers were
      determined. Treatment with PFP (200 and 400 mg/kg) significantly lowered glucose
      concentrations compared to the control group. Serum cholesterol, triglycerides,
      and urine glucose and ketones in animals treated with PFP also decreased. There
      was a significant decrease in the concentrations of malondialdehyde and nitric
      oxide, whereas concentrations of superoxide dismutase, catalase, and reduced
      glutathione were restored. Therefore, these results suggest that PFPs may
      ameliorate hyperglycemia and hypercholesteremia associated with diabetes. Thus
      PFPs could be used as adjunct therapy along with first-line therapy in type 2
      diabetes mellitus. 

PMID- 24941160
TI  - The role of polyunsaturated omega-3 fatty acid eicosapentaenoic acid-derived
      resolvin E1 (RvE1) in bone preservation.
AB  - Resolvin E1 (RvE1) is a recently discovered lipid-derived mediator that is
      endogenously synthesized from the polyunsaturated fatty acid eicosapentaenoic
      acid. RvE1 is locally generated in response to inflammation where it enhances the
      resolution phase of inflammation by diminishing neutrophil chemotaxis and by
      enhancing nonphlogistic macrophage-directed clearance of apoptotic neutrophils.
      RvE1 was also found to be effective in preventing and restoring bone loss in the
      inflammatory bone disease periodontitis. This review examines experimental
      evidence on RvEl's actions in bone. Current data indicate that in addition to
      anti-inflammatory actions, RvE1 also directly acts on bone cells and promotes
      bone preservation. 

PMID- 24941161
TI  - Zn(II)- or Rh(I)-catalyzed rearrangement of silylated [1,1'-bi(cyclopropan)]-2'
      en-1-ols.
AB  - The rearrangement reactions of silylated alcohols bearing the highly strained
      structures of cyclopropene and cyclopropanol connected in adjacent positions have
      been studied under ZnI2- and Rh(I)-catalyzed conditions. The results show
      intriguing carbon skeletal reorganizations of such system under these conditions.
      The ZnI2-catalyzed reaction proceeds with C-O cleavage and the rearrangement of
      the resultant carbon cation, leading to the breaking of the C-C single bond that
      connects two three-memebered rings. In contrast, the Rh(I)-catalyzed reaction
      involves sigma-bond oxidative addition of the cyclopropene moiety, followed by
      beta-carbon elimination of the cyclopropane moiety. 

PMID- 24941163
TI  - The effects of the king oyster mushroom Pleurotus eryngii (higher Basidiomycetes)
      on glycemic control in alloxan-induced diabetic mice.
AB  - The purpose of this study is to investigate the effects of Pleurotus eryngii on
      glycemic metabolism. Alloxan-induced hyperglycemic mice were used to study the
      effects of P. eryngii on blood glucose, glycohemoglobin, insulin secretion,
      damaged pancreatic beta-cells, total antioxidant status (TAOS), and hepatic
      glycogen in hyperglycemic mice. Sixty diabetic mice were divided equally into 5
      groups: the alloxan (AX)-induced hyperglycemic group, the AX and glibenclamide
      (GLI)-treated group, the AX and P. eryngii extracts (PEEs) 50-treated group (PEE
      50 mg/kg), the AX and PEE100-treated group (PEE 100 mg/kg), and the AX and PEE200
      treated group (PEE 200 mg/kg). The other 12 normal mice were injected
      intravenously with the normal saline and used as the control group. After PEE
      (100 and 200 mg/kg) was orally administered to the mice over 5 weeks, blood
      glucose and HbAlc were significantly decreased in AX-induced hyperglycemic mice
      (P < 0.05 and P < 0.01, respectively), whereas the level of insulin secretion was
      markedly elevated in (P < 0.05). The pancreatic beta-cells damaged by AX
      partially and gradually recovered after PPE extract was administered to the
      hyperglycemic mice for 35 days. In addition, PEE treatment gradually increased
      the body weight and significantly increased the concentration of hepatic glycogen
      in hyperglycemic mice (P < 0.05). The results suggest that the action of PPE on
      glycemic metabolism occurs via increasing glycogen and insulin concentrations as
      well as recovering injured beta-cells and reducing free radical damage. PPE may
      become a new potential hypoglycemic food for hyperglycemic people. 

PMID- 24941164
TI  - Medicinal and antimicrobial role of the oyster culinary-medicinal mushroom
      Pleurotus ostreatus (higher Basidiomycetes) cultivated on banana agrowastes in
      India.
AB  - Oyster mushrooms, species of the genus Pleurotus, are recognized for producing
      secondary metabolites with important medicinal properties. Investigations were
      carried out to evaluate the antioxidative and antimicrobial properties of the
      edible mushroom Pleurotus ostreatus (MTCC142) extracts cultivated on banana
      agrowastes. Ethanolic extracts showed antimicrobial activities against gram
      positive and gram-negative bacteria, and their in vitro antifungal activities
      against all fungi tested revealed a promising role. Qualitative phytochemical
      analysis of Pleurotus grown on yeast dextrose broth and banana agrowaste
      confirmed the presence of steroids, cardiac glycosides, terpenoids, and
      alkaloids, whereas ethanolic extract after 40 days exhibited a phenol
      concentration of 521.67 ug/mL in banana waste compared to 155 ug/mL in yeast
      dextrose broth. The minimum inhibitory concentration of ethanolic extracts ranged
      from 19.74 to 56.84 mg/mL and 35.53 to 102.31 mg/mL in solid-state and submerged
      grown mycelium extracts, respectively, after 40 days. Moreover, banana agrowaste
      could be a significant economic source for the production of the oyster mushroom
      P. ostreatus. The nutritive, medicinal, and antimicrobial properties of P.
      ostreatus can be used to develop a new nutraceutical formulation; it can also be
      used as an additive to routine and fast food. 

PMID- 24941165
TI  - In vitro anti-proliferative effects on NB4 human leukemia cells and
      physicochemical screening of Pleurotus sp. (higher Basidiomycetes) mycelia from
      Cuba.
AB  - This study examined the phytochemical profile and the in vitro anti-proliferative
      effects of a hot water mycelial extract from the edible mushroom Pleurotus sp. on
      NB4 human leukemia cells. Flow-cytometry analyses were used to measure cell
      viability, cell cycle, and apoptosis in cells incubated 24 h with the extract at
      doses of 100 and 200 ug/mL. Pleurotus sp. extract reduced cell viability,
      particularly at the concentration of 200 ug/mL to 82% compared to control cells,
      and induced apoptosis demonstrated by an increase in the number of annexin V
      FITC+ cells (25% at 200 ug/mL). The NB4 cells were arrested in the G2/M phase
      thus supporting a cell-cycle dependent anticancer mechanism. Although
      carbohydrates (76.8%, w/w) appear to be the most important antitumor compound,
      secondary metabolites-like phenolics would also contribute to the anti
      proliferative activity. The results indicate that Pleurotus sp. mycelia obtained
      by submerged fermentation may be an interesting renewable resource for developing
      functional foods and new antitumor therapeutic agents. 

PMID- 24941166
TI  - Isolation and purification of a polysaccharide from the caterpillar medicinal
      mushroom Cordyceps militaris (Ascomycetes) fruit bodies and its immunomodulation
      of RAW 264.7 macrophages.
AB  - A novel polysaccharide (CP2-S) was purified from Cordyceps militaris fruit bodies
      by hot water extraction, ethanol precipitation, DEAE-Sepharose Fast Flow and
      Sephacryl S-400 high-resolution chromatography. The polysaccharide had a
      molecular weight of 5.938 * 10(6) g/mol and was mainly composed of glucose. CP2-S
      had carbohydrate content estimated to be 100% using the phenol-sulfuric acid
      method. Immunostimulating experiments in vitro indicated that CP2-S could
      stimulate nitric oxide production, phagocytosis, respiratory burst activity, and
      secretion of interleukin-1beta and interleukin-2 of macrophages, suggesting that
      this water-soluble polysaccharide from the fruit body of C. militaris is a
      natural immunostimulating polysaccharide with potential for further application.

PMID- 24941167
TI  - Solid-substrate fermentation of wheat grains by mycelia of indigenous species of
      the genus Ganoderma (higher Basidiomycetes) to enhance the antioxidant
      activities.
AB  - Species of the genus Ganoderma are a cosmopolitan wood decaying white rot fungi,
      which has been used by the Asians for therapeutic purposes for centuries. In the
      present study, solid-substrate fermentation (SSF) of wheat grains (Triticum
      aestivum L.) was carried out with indigenous Ganoderma australe (KUM60813) and G.
      neo-japonicum (KUM61076) selected based on ethnomycological knowledge. G. lucidum
      (VITA GL) (a commercial strain) was also included in the study. Antioxidant
      activities of the crude ethanol and aqueous extracts of the fermented and
      unfermented wheat grains were investigated by ferric reducing antioxidant power
      (FRAP), Trolox equivalent antioxidant capacity (TEAC), diphenyl-1-picryl-hydrazyl
      (DPPH) free radical scavenging ability, and lipid peroxidation assay. Among the
      six mycelia extracts tested, the ethanol extract from wheat fermented with
      KUM61076 mycelia showed the most potent antioxidant activities, whereas the
      ethanol extract of wheat grains fermented with KUM60813 mycelia has a good
      potential in protecting frying oils against oxidation. Total phenolic content
      (TPC) in the ethanol extracts were higher than that in the aqueous extract. The
      wheat grains fermented with G. australe (KUM60813) and G. neo-japonicum KUM61076
      have greater antioxidant potential compared to the commercially available G.
      lucidum (VITA GL). The antioxidant activities of the mycelia extracts had a
      positive correlation with their phenolic contents. Thus phenolic compounds may
      play a vital role in the antioxidant activities of the selected Ganoderma spp. 

PMID- 24941168
TI  - Dog intoxication by lizard's claw mushroom, Lysurus cruciatus (higher
      Basidiomycetes) in southern Brazil.
AB  - A case of mushroom poisoning of a dog caused by a phalloid fungus is reported for
      the first time. The phalloid caused gastrointestinal syndrome in a 1-year-old
      dog, and was identified as Lysurus cruciatus, a common phalloid fungus in
      southern Brazil. 

PMID- 24941169
TI  - Chemical composition and nutritional and medicinal value of fruit bodies and
      submerged cultured mycelia of culinary-medicinal higher Basidiomycetes mushrooms.
AB  - This research gives the results of a proximate analysis (moisture, ash, crude
      protein, fat, total carbohydrates, and total energy); a bioactive compounds
      analysis (gamma-aminobutyric acid [GABA], ergothioneine, lovastatin, and
      cordycepin); fatty acid and amino acid analysis; and an analysis of macro- and
      microelement content of fruit bodies and mycelia of 15 higher Basidiomycetes
      medicinal mushroom strains belonging to 12 species. The results obtained
      demonstrate that almost all investigated mushrooms were found to be good sources
      of proteins and carbohydrates, with content varying in the ranges of 8.6-42.5%
      and 42.9-83.6%, respectively. Different species exhibited distinct free amino
      acid profiles. The total amino acid content was highest in Ophiocordyceps
      sinensis (MB) (23.84 mg/g) and Cordyceps militaris (FB) (23.69 mg/g). The
      quantification of the identified fatty acids indicated that, in general, palmitic
      acid, oleic acid, stearic acid, and linoleic acid were the major fatty acids. The
      micro- and macroelement compositions were studied, and the highest results were
      (as milligrams per kilogram) 224-7307 for calcium, 1668-38564 for potassium, 1091
      11676 for phosphorus, and 5-97 for zinc. Bioactive components were lovastatin,
      GABA, and ergothioneine, which are commonly found in most mushrooms. C. militaris
      (FB), Pleurotus ostreatus (FB), and Coprinus comatus (FB) were most abundant and
      contained a high amount of GABA (756.30 MUg/g, 1304.99 MUg/g, 1092.45 MUg/g,
      respectively) and ergothioneine (409.88 MUg/g, 2443.53 MUg/g, 764.35 MUg/g,
      respectively). The highest lovastatin content was observed in Hericium erinaceus
      (FB) (14.38 MUg/g) and Ganoderma lucidum (FB) (11.54 MUg/g). In contrast to C.
      militaris (FB), cordycepin was not detected in O. sinensis (MB). The fruit body
      biomass of C. militaris cordycepin content reached 1.743 mg/g dry weight. The
      nutritional values of the mushroom species studied here could potentially be used
      in well-balanced diets and as sources of bioactive compounds. 

PMID- 24941170
TI  - The optimum submerged culture condition of the culinary-medicinal white jelly
      mushroom (Tremellomycetes) and its antioxidant properties.
AB  - Tremella fuciformis is a natural edible and medicinal mushroom commercially
      available in Taiwan. In this study, the effects of initial pH, incubation time,
      and various media to optimize exopolysaccharide (EPS) production by T. fuciformis
      were evaluated in shake flasks and a bioreactor. The antioxidant properties were
      investigated. The results showed that using potato dextrose broth medium (pH 9)
      and a 48-hour incubation time in a shake flask was the most efficient condition
      from which to obtain maximum EPS. However, the quantity of EPS from different
      initial pH values (5-9) was not significantly different. Total polyphenol and
      beta-glucan contents from every EPS sample (pH 5-9) were evaluated. T. fuciformis
      polysaccharides (10 mg/mL, pH 9) could scavenge 40.63% of 1,1-diphenyl-2
      picrylhydrazyl radicals. The chelating abilities of ferrous ion of all extracts
      reached more than 80%. EPS extract from the initial pH value of 9 showed the
      highest reducing power among the other pH values (half maximal effective
      concentration = 5.97 mg/mL). The EPS from T. fuciformis was noncytotoxic to mouse
      skin fibroblasts (NIH/3T3), and survival rates were more than 100% using MTT
      assay. The samples were used to analyze the scavenging activity against oxidative
      damage induced by ultraviolet B radiation and hydrogen peroxide. The results
      showed the antioxidant activity occurred in a dose-dependent manner (P < 0.05).
      Furthermore, these findings prove that the EPS of T. fuciformis from submerged
      culture possess antioxidant properties and can be used as an alternative
      treatment for cell protection. 

PMID- 24941172
TI  - Intraguild interactions between two egg parasitoids of a true bug in semi-field
      and field conditions.
AB  - Research on interspecific competitive interactions among insect parasitoids has
      often been characterized by laboratory studies in which host insects are exposed
      to female parasitoids of different species in various sequences and combinations.
      In the last years, an increasing number of studies have investigated
      interspecific interactions under field and semi-field conditions although just a
      few number of works focused on egg parasitoids. In this work, we undertook a two
      year study to investigate interspecific interactions between Trissolcus basalis
      (Wollaston) (Hymenoptera: Platygastridae) and Ooencyrtus telenomicida (Vassiliev)
      (Hymenoptera: Encyrtidae), two egg parasitoids of the pest Nezara viridula (L.)
      (Heteroptera: Pentatomidae) that co-occur in cultivated crops. Under semi-field
      (in out-door mesh cages) and field conditions, we investigated: 1) the seasonal
      occurrence of competing parasitoid species on sentinel egg masses; 2) the impact
      achieved by competing species on the shared host on naturally laid egg masses; 3)
      the outcome of intraguild interactions under controlled conditions. Results from
      sentinel egg masses showed that T. basalis occurs in May and successfully
      parasitizes hosts until the end of September/beginning of October, whereas O.
      telenomicida is mainly occurring in July-August. In both years, it was found that
      T. basalis is predominant. From naturally laid egg masses, results indicated that
      T. basalis achieves higher impact on the hosts, even in those egg masses which
      are parasitized by more than one female of different species ( = 
      multiparasitism). Results from manipulating intraguild interactions showed that
      T. basalis achieves higher impact on N. viridula when released alone, but it
      suffers from competition with O. telenomicida. The ecological factors that play a
      role in intraguild interactions in the context of biological control perspective
      are discussed. 

PMID- 24941171
TI  - MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model
      reveals epigenetic alterations during chronic colitis malignant transformation.
AB  - Our previous studies have demonstrated that genetic deletion of the Muc2 gene
      causes colorectal cancers in mice. The current study further showed that at the
      early stage (<3 months) the Muc2 knockout mice spontaneously developed chronic
      inflammation in colon and rectum, similar pathological features as human colitis;
      and at the late stage (>3 months) the mice exhibited colorectal cancer, including
      a unique phenotype of rectal prolapsed (rectal severe inflammation and
      adenocarcinoma). Thus, the age of 3 months might be the key point of the
      transition from chronic inflammation to cancer. To determine the mechanisms of
      the malignant transformation, we conducted miRNA array on the colonic epithelial
      cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed
      differential expression of miRNAs (i.e. lower or higher expression enrichments)
      in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on
      relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR
      150) were validate and were found significantly downregulated in human colitis
      and colorectal cancer tissues. The network of the targets of these miRNAs was
      characterized, and interestedly, miRNA-associated cytokines were significantly
      increased in Muc2-/-mice. This is the first to reveal the importance of aberrant
      expression of miRNAs in dynamically transformation from chronic colitis to
      colitis-associated cancer. These findings shed light on revealing the mechanisms
      of chronic colitis malignant transformation. 

PMID- 24941173
TI  - SAPS 3 works properly in cardiac surgery.

PMID- 24941174
TI  - The importance of pericentric inversions in the karyotypic diversification of the
      species Loricariichthys anus and Loricariichthys platymetopon.
AB  - Catfishes of the genus Loricariichthys are widely distributed in the Platina
      Basin. Considering that the cytogenetic knowledge of Loricariichythys is
      underestimated, this study assessed Loricariichthys anus and Loricariichthys
      platymetopon through different chromosome bandings, to define the mechanisms
      determining the variability in these species. Cytogenetic analyses evidenced a
      high degree of similarity in relation to the 2n (54 chromosomes), as well as to
      the distribution of heterochromatin. Despite the apparent conservatism, it was
      possible to differentiate between these species, especially in relation to the
      location of the 18S rDNA genes. An interpopulation variation in the karyotype
      formula was detected only in L. anus, showing the existence of different
      karyotypes, probably due to the geographical isolation between Laguna dos Patos
      and Tramandai River. The maintenance of the 2n=54, along with the different
      karyotypes observed in L. anus, the differential nucleolus organizer regions
      position, as well as the sexual chromosome system ZZ/ZW in L. platymetopon, makes
      the participation of pericentric inversions in the karyotypic evolution of these
      species evident. These structural rearrangements were important for chromosome
      evolution of these two species, because they probably promoted the postzygotic
      barriers to reproduction, significantly contributing to the speciation process
      between them.

PMID- 24941175
TI  - Comment to: Haque S, Khan A, Sharma A, Sundararajan S: Technical tip: tightrope
      fixation of neer type II distal clavicle fracture supported by a case series. Pol
      Orthop Traumatol, 2014; 79: 19-22.
AB  - Additional suture anchor fixation to coracoclaviculer area with precountered
      distal clavicle locking plate allows an anatomic reduction with bone-bone contact
      and gives additional neutralisation effect with coracoclavicular suture anchor
      fixation against the trapezius muscle pulling effect .Event though the effeciency
      of this technique reported by other authors,still there is a few articles and
      cases reported.In the terms of proving the efficiency of the combination
      technique we would like to stress to contribute the published article by Haque et
      al.

PMID- 24941176
TI  - Tuberculosis control in New York City--a changing landscape.

PMID- 24941179
TI  - Diagnostic clinical genome and exome sequencing.

PMID- 24941180
TI  - Images in clinical medicine. Mondor's disease.

PMID- 24941178
TI  - Antidepressant use in pregnancy and the risk of cardiac defects.
AB  - BACKGROUND: Whether the use of selective serotonin-reuptake inhibitors (SSRIs)
      and other antidepressants during pregnancy is associated with an increased risk
      of congenital cardiac defects is uncertain. In particular, there are concerns
      about a possible association between paroxetine use and right ventricular outflow
      tract obstruction and between sertraline use and ventricular septal defects.
      METHODS: We performed a cohort study nested in the nationwide Medicaid Analytic
      eXtract for the period 2000 through 2007. The study included 949,504 pregnant
      women who were enrolled in Medicaid during the period from 3 months before the
      last menstrual period through 1 month after delivery and their liveborn infants.
      We compared the risk of major cardiac defects among infants born to women who
      took antidepressants during the first trimester with the risk among infants born
      to women who did not use antidepressants, with an unadjusted analysis and
      analyses that restricted the cohort to women with depression and that used
      propensity-score adjustment to control for depression severity and other
      potential confounders. RESULTS: A total of 64,389 women (6.8%) used
      antidepressants during the first trimester. Overall, 6403 infants who were not
      exposed to antidepressants were born with a cardiac defect (72.3 infants with a
      cardiac defect per 10,000 infants), as compared with 580 infants with exposure
      (90.1 per 10,000 infants). Associations between antidepressant use and cardiac
      defects were attenuated with increasing levels of adjustment for confounding. The
      relative risks of any cardiac defect with the use of SSRIs were 1.25 (95%
      confidence interval [CI], 1.13 to 1.38) in the unadjusted analysis, 1.12 (95% CI,
      1.00 to 1.26) in the analysis restricted to women with depression, and 1.06 (95%
      CI, 0.93 to 1.22) in the fully adjusted analysis restricted to women with
      depression. We found no significant association between the use of paroxetine and
      right ventricular outflow tract obstruction (relative risk, 1.07; 95% CI, 0.59 to
      1.93) or between the use of sertraline and ventricular septal defects (relative
      risk, 1.04; 95% CI, 0.76 to 1.41). CONCLUSIONS: The results of this large,
      population-based cohort study suggested no substantial increase in the risk of
      cardiac malformations attributable to antidepressant use during the first
      trimester. (Funded by the Agency for Healthcare Research and Quality and the
      National Institutes of Health.).

PMID- 24941181
TI  - Case records of the Massachusetts General Hospital. Case 19-2014. A 19-year-old
      woman with headache, fever, stiff neck, and mental-status changes.

PMID- 24941182
TI  - Clinical decisions. Screening an asymptomatic person for genetic risk.

PMID- 24941177
TI  - Tofacitinib versus methotrexate in rheumatoid arthritis.
AB  - BACKGROUND: Methotrexate is the most frequently used first-line antirheumatic
      drug. We report the findings of a phase 3 study of monotherapy with tofacitinib,
      an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in
      patients with rheumatoid arthritis who had not previously received methotrexate
      or therapeutic doses of methotrexate. METHODS: We randomly assigned 958 patients
      to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose
      that was incrementally increased to 20 mg per week over 8 weeks; 956 patients
      received a study drug. The coprimary end points at month 6 were the mean change
      from baseline in the van der Heijde modified total Sharp score (which ranges from
      0 to 448, with higher scores indicating greater structural joint damage) and the
      proportion of patients with an American College of Rheumatology (ACR) 70 response
      (>=70% reduction in the number of both tender and swollen joints and >=70%
      improvement in three of five other criteria: the patient's assessment of pain,
      level of disability, C-reactive protein level or erythrocyte sedimentation rate,
      global assessment of disease by the patient, and global assessment of disease by
      the physician). RESULTS: Mean changes in the modified total Sharp score from
      baseline to month 6 were significantly smaller in the tofacitinib groups than in
      the methotrexate group, but changes were modest in all three groups (0.2 points
      in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as
      compared with 0.8 points in the methotrexate group [P<0.001 for both
      comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group
      and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with
      12.0% of patients in the methotrexate group (P<0.001 for both comparisons).
      Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and
      in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer
      (including three cases of lymphoma) developed in 5 patients who received
      tofacitinib and in 1 patient who received methotrexate. Tofacitinib was
      associated with increases in creatinine levels and in low-density and high
      density lipoprotein cholesterol levels. CONCLUSIONS: In patients who had not
      previously received methotrexate or therapeutic doses of methotrexate,
      tofacitinib monotherapy was superior to methotrexate in reducing signs and
      symptoms of rheumatoid arthritis and inhibiting the progression of structural
      joint damage. The benefits of tofacitinib need to be considered in the context of
      the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov
      number, NCT01039688.).

PMID- 24941183
TI  - Ribavirin for chronic hepatitis E virus infection.

PMID- 24941184
TI  - Ribavirin for chronic hepatitis E virus infection.

PMID- 24941185
TI  - Ribavirin for chronic hepatitis E virus infection.

PMID- 24941186
TI  - Ribavirin for chronic hepatitis E virus infection.

PMID- 24941187
TI  - Sirolimus in severe hyperinsulinemic hypoglycemia.

PMID- 24941188
TI  - Sirolimus in severe hyperinsulinemic hypoglycemia.

PMID- 24941189
TI  - Nutrition in the acute phase of critical illness.

PMID- 24941190
TI  - Nutrition in the acute phase of critical illness.

PMID- 24941191
TI  - Nutrition in the acute phase of critical illness.

PMID- 24941192
TI  - Nutrition in the acute phase of critical illness.

PMID- 24941193
TI  - Global biomedical R&D expenditures.

PMID- 24941194
TI  - Global biomedical R&D expenditures.

PMID- 24941195
TI  - Emphysematous aortitis after endovascular graft.

PMID- 24941196
TI  - Emphysematous aortitis after endovascular graft.

PMID- 24941197
TI  - Physician attitudes and experience with permit applications for concealed
      weapons.

PMID- 24941198
TI  - Images in clinical medicine. Roth spots in infective endocarditis.

PMID- 24941199
TI  - Psychological interventions for individuals with cystic fibrosis and their
      families.
AB  - BACKGROUND: With increasing survival estimates for individuals with cystic
      fibrosis, long-term management has become an important focus. Psychological
      interventions are largely concerned with adherence to treatment, emotional and
      social adaptation and health-related quality of life. We are unaware of any
      relevant systematic reviews. OBJECTIVES: To determine whether psychological
      interventions for people with cystic fibrosis provide significant psychosocial
      and physical benefits in addition to standard medical care. SEARCH METHODS:
      Studies were identified from two Cochrane trials registers (Cystic Fibrosis and
      Genetic Disorders Group; Depression, Anxiety and Neurosis Group), Ovid MEDLINE
      and PsychINFO; unpublished trials were located through professional networks and
      Listserves. Most recent search of the Cystic Fibrosis and Genetic Disorders
      Group's register: 19 December 2013.Most recent search of the Depression, Anxiety
      and Neurosis Group's register: 12 November 2013. SELECTION CRITERIA: Randomised
      controlled studies of a broad range of psychological interventions evaluating
      subjective and objective health outcomes, such as quality of life or pulmonary
      function, in individuals of all ages with cystic fibrosis and their immediate
      family. We were interested in psychological interventions, including
      psychological methods within the scope of psychotherapeutic or psychosomatic
      mechanism of action (e.g. cognitive behavioural, cognitive, family systems or
      systemic, psycho-dynamic, or other, e.g. supportive, relaxation, or biofeedback),
      which were aimed at improving psychological and psychosocial outcomes (e.g.
      quality of life, levels of stress or distress, psychopathology, etc.), adaptation
      to disease management and physiological outcomes. DATA COLLECTION AND ANALYSIS:
      Three authors were involved in selecting the eligible studies and two of these
      authors assessed their risk of bias. MAIN RESULTS: The review includes 16 studies
      (eight new studies included in this update) representing data from 556
      participants. Studies are diverse in their design and their methods. They cover
      interventions with generic approaches, as well as interventions developed
      specifically to target disease-specific symptoms and problems in people with
      cystic fibrosis. These include cognitive behavioural interventions to improve
      adherence to nutrition or psychosocial adjustment, cognitive interventions to
      improve adherence or those associated with decision making in lung
      transplantation, a community-based support intervention and other interventions,
      such as self-hypnosis, respiratory muscle biofeedback, music therapy, dance and
      movement therapy, and a tele-medicine intervention to support patients awaiting
      transplantation.A substantial proportion of outcomes relate to adherence, changes
      in physical status or other specific treatment concerns during the chronic phase
      of the disease.There is some evidence that behavioural interventions targeting
      nutrition and growth in children (4 to 12 years) with cystic fibrosis are
      effective in the short term. Evidence was found that providing a structured
      decision-making tool for patients considering lung transplantation improves
      patients' knowledge of and expectations about the transplant, and reduces
      decisional conflict in the short term. One study about training in biofeedback
      assisted breathing demonstrated some evidence that it improved some lung function
      measurements. Currently there is insufficient evidence for interventions aimed at
      other aspects of the disease process. AUTHORS' CONCLUSIONS: Currently,
      insufficient evidence exists on psychological interventions or approaches to
      support people with cystic fibrosis and their caregivers, although some of the
      studies were promising. Due to the heterogeneity between studies, more of each
      type of intervention are needed to support preliminary evidence. Multicentre
      studies, with consequent funding implications, are needed to increase the sample
      size of these studies and enhance the statistical power and precision to detect
      important findings. In addition, multicentre studies could improve the
      generalisation of results by minimizing centre or therapist effects.
      Psychological interventions should be targeted to illness-specific symptoms or
      behaviours to demonstrate efficacy.

PMID- 24941201
TI  - Abstracts presented at the 2013 Annual Symposium of the Belgische Vereniging voor
      Klinische Chemie, Societe Belge de Chimie Clinique.

PMID- 24941202
TI  - Magnetic assembly and annealing of colloidal lattices and superlattices.
AB  - The ability to assemble mesoscopic colloidal lattices above a surface is
      important for fundamental studies related with nucleation and crystallization but
      also for a variety of technological applications in photonics and
      microengineering. Current techniques based on particle sedimentation above a
      lithographic template are limited by a slow deposition process and by the use of
      static templates, which make difficult to implement fast annealing procedures.
      Here it is demonstrated a method to realize and anneal a series of colloidal
      lattices displaying triangular, honeycomb, or kagome-like symmetry above a
      structure magnetic substrate. By using a binary mixture of particles,
      superlattices can be realized increasing further the variety and complexity of
      the colloidal patterns which can be produced. 

PMID- 24941203
TI  - Medication algorithm for mood disorders: Present status and future direction in
      Japan.
AB  - Medication algorithms have been used extensively in treating psychiatric
      patients, while geographic variations among these reflect the local history of
      the practice of psychiatry in each region. Here we review algorithms used for
      mood disorders in Japan in terms of their utility, problems, and possible future
      development. The first Japanese algorithm for mood disorders was completed in
      1997 by the Japanese Psychopharmacology Algorithm Project (JPAP). Development of
      the JPAP algorithm was evidence-based, giving major but not exclusive weight to
      clinical trial outcomes. Unlike others, the JPAP algorithm suggests possible
      addition of a benzodiazepine to first-line antidepressant treatment for major
      depression. When the first-choice antidepressant fails, the algorithm recommends
      monotherapy with another antidepressant over "add-on" therapy. Clinical problems
      with the JPAP algorithm include lack of guidance concerning how to change from
      one drug to another. Psychiatry in Japan provides less formal structure for post
      graduate education and undertakes less communication with the general public than
      in many countries. This makes use of an algorithm important for improving quality
      of practice, provided that clinicians remain aware of the advantages,
      limitations, and problems of algorithms. 

PMID- 24941200
TI  - Mechanisms of U87 astrocytoma cell uptake and trafficking of monomeric versus
      protofibril Alzheimer's disease amyloid-beta proteins.
AB  - A significant hallmark of Alzheimer's disease is the formation of senile plaques
      in the brain due to the unbalanced levels of amyloid-beta (Abeta). However,
      although how Abeta is produced from amyloid precursor proteins is well
      understood, little is known regarding the clearance and metabolism of various
      Abeta aggregates from the brain. Similarly, little is known regarding how
      astrocytes internalize and degrade Abeta, although astrocytes are known to play
      an important role in plaque maintenance and Abeta clearance. The objective of
      this study is to investigate the cellular mechanisms that mediate the
      internalization of soluble monomeric versus oligomeric Abeta by astrocytes. We
      used a combination of laser confocal microscopy and genetic and pharmacological
      experiments to dissect the internalization of sAbeta42 and oAbeta42 and their
      postendocytic transport by U87 human brain astrocytoma cell line. Both Abeta42
      species were internalized by U87 cells through fluid phase macropinocytosis,
      which required dynamin 2. Depleting LDL receptor-related protein 1 (LRP1)
      decreased sAbeta42 uptake more significantly than that of oAbeta42. We finally
      show that both Abeta42 species were rapidly transported to lysosomes through an
      endolytic pathway and subjected to proteolysis after internalization, which had
      no significant toxic effects to the U87 cells under relatively low
      concentrations. We propose that macropinocytic sAbeta42 and oAbeta42 uptake and
      their subsequent proteolytic degradation in astroglial cells is a significant
      mechanism underlying Abeta clearance from the extracellular milieu. Understanding
      the molecular events involved in astrocytic Abeta internalization may identify
      potential therapeutic targets for Alzheimer's disease. 

PMID- 24941204
TI  - Long-term assessment of the efficacy and tolerability of risperidone in early
      schizophrenia: An international multicenter study.
AB  - OBJECTIVE The aim of this open multicenter international study was an assessment
      of the efficacy and tolerability of risperidone administered for 12 months in
      patients with early schizophrenia. METHODS Two hundred and five patients, 113
      male and 92 female, aged 15-46 years were included. The mean daily risperidone
      dose was 3.3+/-1.4 mg/day and in three-quarters of patients the dose was in the
      range of 2-4 mg. For psychometric assessment the Positive and Negative Syndrome
      Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS) and the Montgomery
      Asberg Depression Rating Scale (MADRS) were used. RESULTS One hundred and thirty
      two patients (64%) completed the study. Significant improvement (at least 20%
      reduction) was found on PANSS subscales for positive symptoms (89% of patients),
      negative symptoms (77% of patients), as well as for depressive symptoms measured
      by MADRS (78% of patients). Parkinsonian symptoms occurred in 53 patients
      (26.5%), necessitating the use of anticholinergic drugs. Risperidone treatment
      did not exert a significant effect on vital signs and on ECG recordings.
      CONCLUSION The results suggest that, in a substantial proportion of patients with
      early schizophrenia, risperidone can be successfully used for initiation of
      pharmacological treatment of schizophrenia and then be continued on the long-term
      basis. 

PMID- 24941205
TI  - Suicidal behaviour and intensity of psychiatric care in a region at high risk for
      suicide.
AB  - BACKGROUND Suicidal behaviour represents a social and health-related issue of
      prime importance in both the general and psychiatric population. People with
      mental illness are at great risk of suicide, but indirect evidence suggests that
      the treatment of psychiatric disorders may prevent suicide. The aim of our study
      was to compare the risk of suicide in the population of psychiatric patients with
      that of the general population in Friuli Venezia-Giulia (FVG). METHOD We analyzed
      the suicide rates, based on the official statistical database, relating to the
      resident population in FVG during the years 1998-1999. The sucide rates (per 100
      000 subjects) were standardised by sex and age. The characteristics of suicidal
      behaviour in subjects who had been in contact with (Community Mental Health
      Centres) CMHC (n=65) were compared with that of suicidal subjects not in contact
      (n=237). RESULTS There was an increase in the suicide phenomenon in the elderly
      population in FVG over the tested period. The rates were three times higher in
      males than in females. The rates of patients in contact with CMHC in 1998 and in
      1999 were, respectively, 14 and 20 times higher than that of the general
      population. Most suicidal schizophrenics and 37% of the depressed patients have
      been previously hospitalised. CONCLUSION The population of north-eastern Italy is
      at high risk of suicide compared to other regions. The mortality ratio of
      psychiatric subjects who commit suicide in our sample is elevated. Since Italian
      community-oriented services rely less on hospitalisation than in other countries,
      the fact that about 50% of suicidal psychiatric patients have been previously
      admitted in a psychiatric ward may indicate that previous hospitalisation is a
      hierarchic factor related to suicide. 

PMID- 24941206
TI  - A study to evaluate the use of extended release divalproex.
AB  - BACKGROUND Delayed release divalproex has become a mainstay in the treatment of
      many psychiatric conditions. An extended release preparation with different
      pharmacokinetics is now available, but its efficacy in psychiatric patients has
      yet to be established. METHODS The authors report a retrospective chart review of
      psychiatric outpatients treated with extended release divalproex. Fourteen charts
      were identified and reviewed for indications of efficacy and tolerability over a
      10-month period. Case reports were provided for four of the patients. RESULTS Of
      the 14 patients, only one was unable to tolerate the extended release
      preparation. No patient was discontinued due to lack of efficacy or for safety
      reasons. Among the patients remaining on the extended release preparation, only
      minor side effects were reported. CONCLUSIONS This chart review suggests that
      extended release divalproex was well tolerated and efficacious in a population of
      psychiatric outpatients. Further studies are needed to validate these findings. 

PMID- 24941207
TI  - Hepatotoxicity, leucopenia and neutropenia associated with olanzapine therapy.
AB  - Hepatotoxicity, leukopenia and neutropenia are rarely associated with atypical
      antipsychotic drug therapy. The authors describe a case of a schizophrenic
      patient, who was treated twice with olanzapine, and who developed an increase of
      hepatic enzymes, jaundice, reduced WBC, neutropenia, and a high temperature. The
      patient was diagnosed as suffering from hepatocellular hepatitis, neutropenia and
      leucopenia. Neuroleptic treatment was discontinued immediately and the patient
      exhibited consequential clinical improvement. A review of the literature is
      included. 

PMID- 24941208
TI  - Fluoxetine treatment of selective mutism in pervasive developmental disorder.
AB  - We report the successful treatment of selective mutism in a child with pervasive
      developmental disorder (PDD). There are several studies and case reports in which
      Fluoxetine has been reported effective in diminishing adult social anxiety and
      increasing speech in public settings. The literature is much smaller for
      children. The efficacy of fluoxetine supports the argument that selective mutism
      is a developmental equivalent of social anxiety disorder. To our knowledge this
      is the first description of successful treatment when the selective mutism is
      complicated by PDD. 

PMID- 24941209
TI  - Remission of mood disorder with psychotic features after treatment with
      mirtazapine.
AB  - The antidepressant mirtazapine enhances both noradrenergic and serotonergic
      transmission by blocking alpha2-adrenergic presynaptic auto- and heteroreceptors,
      respectively. We here report on three patients with mood disorders with psychotic
      features (two cases with depressive and one with bipolar disorder). Treatment
      with mirtazapine significantly improved not only their depression, but also their
      delusions. Depressive symptoms were only partially responsive and delusions
      unresponsive in all three patients to previous antidepressive and/or
      antipsychotic treatment, and only mirtazapine induced persistent improvement.
      These clinical cases suggest that mirtazapine can be a valid alternative for
      patients with depression with psychotic features and partial treatment
      resistance. 

PMID- 24941210
TI  - Psychiatric findings related to neurological complications in Behcet's disease: A
      short review and a case presentation.
AB  - Behcet's disease affects the skin, mucosa, joints, vascular system, eyes, the
      central nervous system (CNS) and gastrointestinal system. In Behcet's disease,
      the obvious illness mechanism in all organ systems is occlusive vasculitis of
      unknown etiology. CNS involvement in Behcet's disease sometimes causes
      psychiatric disorders. In this paper we discuss a case with neurobehcet disease
      who was admitted with psychotic symptoms. This 29-year-old male patient had
      symptoms of Behcet's disease and concomitant psychiatric symptoms. An advanced
      evaluation of the CNS was performed following unresponsiveness to antipsychotic
      treatment. It was concluded that the psychotic picture was a result of CNS
      involvement related to Behcet's disease. Colchicine was added to the treatment
      and upon discharge the case was in remission. Differences in treatment and
      prognosis between psychiatric disorder due to Behcet's disease and psychiatric
      disorders comorbid to Behcet's disease are discussed. 

PMID- 24941211
TI  - High-dose venlafaxine treatment in a depressed patient with a genetic CYP2D6
      deficiency.
AB  - A female patient (47 years) who suffered from a severe episode of a recurrent
      depression with psychotic symptoms (F33.3) firstly underwent several unsuccessful
      treatments. She was then submitted to a combined treatment with 2*300 mg/day
      extended-release venlafaxine (VEN) and lithium (0.7 mmol/l). She responded within
      7 weeks and, after 9 weeks, she showed full remission. Moreover, she tolerated
      this medication well. Steady-state plasma concentrations of VEN and its
      metabolites and their enantiomers were measured. The concentrations of VEN and
      its metabolite O-demethyl-VEN (ODV) were 1024 and 234 ng/ml, respectively. The
      unusually high concentration of the parent compound in comparison to the
      metabolite is mainly explained by an impaired metabolism of R-VEN in this
      patient, who by genotyping was shown to have a genetic deficiency of CYP2D6. In
      conclusion, in patients suffering from non-response to an antidepressant
      treatment, an individualised treatment strategy should be developed, and
      stereoselective therapeutic drug monitoring and genotyping may be recommended. 

PMID- 24941213
TI  - Neonatal platelets: mediators of primary hemostasis in the developing hemostatic
      system.
AB  - The human hemostatic system is developmentally regulated, resulting in
      qualitative and quantitative differences in the mediators of primary and
      secondary hemostasis as well as fibrinolysis in neonates and infants. Although
      gestational age-related differences in coagulation factor levels occur, the
      existence of a unique neonatal platelet phenotype remains controversial.
      Complicated by difficulties in obtaining adequate neonatal blood volumes with
      which to perform functional assays, ambiguity surrounds the characterization of
      neonatal platelets. Thus, much of the current knowledge of neonatal platelet
      function has been based on studies from cord blood samples. Studies suggest that
      cord blood-derived platelets, as a surrogate for neonatal platelets, are
      hypofunctional when compared with adult platelets. This relative platelet
      dysfunction, combined with a propensity toward thrombocytopenia in the neonatal
      intensive care unit population, creates a clinical conundrum regarding the
      appropriate administration of platelet transfusions. This review provides an
      appraisal of the distinct functional phenotype of neonatal platelets. Neonatal
      platelet transfusion practices and the impact of the relatively hypofunctional
      neonatal platelet on those practices will be considered.

PMID- 24941212
TI  - Efficacy of paracetamol on patent ductus arteriosus closure may be dose
      dependent: evidence from human and murine studies.
AB  - BACKGROUND: We evaluated the clinical effectiveness of variable courses of
      paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on
      the in vitro term and preterm murine ductus arteriosus (DA). METHODS: Neonates
      received one of the following three paracetamol regimens: short course of oral
      paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous
      paracetamol (IVP) for 2-6 d. Pressure myography was used to examine changes in
      vasomotor tone of the preterm and term mouse DA in response to paracetamol or
      indomethacin. Their effect on prostaglandin synthesis by DA explants was measured
      by mass spectroscopy. RESULTS: Twenty-one preterm infants were included. No
      changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became
      less significant and eventually closed in six LCOP infants (n = 7). PDA closure
      was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol
      induced a concentration-dependent constriction of the term mouse DA, up to 30% of
      baseline (P < 0.01), but required >1 umol/l. Indomethacin induced greater DA
      constriction and suppression of prostaglandin synthesis (P < 0.05). CONCLUSION:
      The clinical efficacy of paracetamol on PDA closure may depend on the duration of
      treatment and the mode of administration. Paracetamol is less potent than
      indomethacin for constriction of the mouse DA in vitro.

PMID- 24941214
TI  - Inhibition of IGF-I-related intracellular signaling pathways by proinflammatory
      cytokines in growth plate chondrocytes.
AB  - BACKGROUND: Children with chronic inflammatory diseases suffer from severe growth
      failure associated with resistance toward the anabolic action of insulin-like
      growth factor I (IGF-I). We hypothesized that proinflammatory cytokines interfere
      with IGF-I signaling. METHODS: We used the mesenchymal chondrogenic cell line
      RCJ3.1C5.18 as a model of the growth plate. Cell proliferation was assessed by
      [(3)H]-thymidine-uptake and differentiation by gene expression (quantitative
      reverse-transcriptase PCR) of specific differentiation markers. Key signaling
      molecules of the respective IGF-I-related intracellular pathways were determined
      by western immunoblotting. RESULTS: Coincubation of the proinflammatory cytokines
      interleukin (IL)-1beta (10 ng/ml), IL-6 (100 ng/ml), or tumor necrosis factor
      alpha (50 ng/ml) with IGF-I inhibited IGF-I-driven cell proliferation by 50%,
      while baseline cell proliferation was not altered. These cytokines attenuated the
      IGF-I-induced phosphorylation of AKT as a key signaling molecule of the
      phosphatidylinositol-3 kinase pathway by 30-50% and the phosphorylation of ERK as
      a key signaling molecule of the mitogen-activated protein kinase/extracellular
      signal-regulated kinase pathway by 50-75%. Also, IGF-I-enhanced chondrocyte
      differentiation was inhibited by these proinflammatory cytokines. CONCLUSION: The
      insensitivity toward the anabolic action of IGF-I in the growth plate in
      conditions of chronic inflammation is partially due to inhibition of IGF-I
      specific signaling pathways by proinflammatory cytokines, which affect both IGF-I
      driven chondrocyte proliferation and differentiation.

PMID- 24941215
TI  - The airway microbiome of intubated premature infants: characteristics and changes
      that predict the development of bronchopulmonary dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with perinatal
      inflammatory triggers. Methods targeting bacterial rRNA may improve detection of
      microbial colonization in premature infants. We hypothesize that respiratory
      microbiota differs between preterm infants who develop BPD and those unaffected
      and correlates with inflammatory mediator concentrations. METHODS: Twenty-five
      infants, born at <=32 wk of gestation and intubated in the first 24 h, were
      enrolled. Tracheal aspirates were obtained at intubation and on days 3, 7, and
      28. Bacterial DNA was extracted, and 16S rRNA genes were amplified and sequenced.
      Concentrations of interleukins (IL-1beta, IL-6, IL-8, IL-10, and IL-12), tumor
      necrosis factor-alpha, interferon-gamma, lipopolysaccharide (LPS), and
      lipoteichoic acid (LTA) were measured. Chorioamnionitis was diagnosed by
      histology. BPD was defined as an oxygen requirement at 36 wk postmenstrual age.
      RESULTS: Acinetobacter was the predominant genus in the airways of all infants at
      birth. Ten infants developed BPD and showed reduced bacterial diversity at birth.
      No differences were detected in bacterial diversity, cytokines, LPS, and LTA from
      infants with and without exposure to chorioamnionitis. CONCLUSION: The airways of
      premature infants are not sterile at birth. Reduced diversity of the microbiome
      may be an important factor in the development of BPD and is not associated with
      differences in inflammatory mediators.

PMID- 24941216
TI  - Serum amyloid A is increased in children with abusive head trauma: a gel-based
      proteomic analysis.
AB  - BACKGROUND: Abusive head trauma (AHT) is the leading cause of death from
      traumatic brain injury in infants and young children. Identification of mild AHT
      (Glasgow Coma Scale score: 13-15) is difficult because children can present with
      nonspecific symptoms and with no history of trauma. METHODS: Two-dimensional
      difference gel electrophoresis combined with mass spectrometry was used to
      compare the serum protein profile of children with mild AHT and age-matched
      controls. Protein changes were confirmed by western blots. Western blots were
      performed using serum from children with mild, moderate, and severe AHT to assess
      the effect of injury severity on protein intensity. The protein identified--serum
      amyloid A (SAA)--was then measured by enzyme-linked immunosorbent assay. RESULTS:
      Using serum from 18 mild AHT cases and 20 controls, there were ~1,000 protein
      spots; 2 were significantly different between groups. Both spots were identified
      as SAA. There was no relationship between protein levels and injury severity. SAA
      concentrations measured by enzyme-linked immunosorbent assay were increased in
      cases vs. controls. CONCLUSION: SAA may be a potential biomarker to identify
      children with mild AHT who present for medical care without a history of trauma
      and who might otherwise not be recognized as needing a head computed tomography.

PMID- 24941218
TI  - Millimeter-sized marine plastics: a new pelagic habitat for microorganisms and
      invertebrates.
AB  - Millimeter-sized plastics are abundant in most marine surface waters, and known
      to carry fouling organisms that potentially play key roles in the fate and
      ecological impacts of plastic pollution. In this study we used scanning electron
      microscopy to characterize biodiversity of organisms on the surface of 68 small
      floating plastics (length range = 1.7-24.3 mm, median = 3.2 mm) from Australia
      wide coastal and oceanic, tropical to temperate sample collections. Diatoms were
      the most diverse group of plastic colonizers, represented by 14 genera. We also
      recorded 'epiplastic' coccolithophores (7 genera), bryozoans, barnacles (Lepas
      spp.), a dinoflagellate (Ceratium), an isopod (Asellota), a marine worm, marine
      insect eggs (Halobates sp.), as well as rounded, elongated, and spiral cells
      putatively identified as bacteria, cyanobacteria, and fungi. Furthermore, we
      observed a variety of plastic surface microtextures, including pits and grooves
      conforming to the shape of microorganisms, suggesting that biota may play an
      important role in plastic degradation. This study highlights how anthropogenic
      millimeter-sized polymers have created a new pelagic habitat for microorganisms
      and invertebrates. The ecological ramifications of this phenomenon for marine
      organism dispersal, ocean productivity, and biotransfer of plastic-associated
      pollutants, remains to be elucidated.

PMID- 24941221
TI  - alpha-Borylcarbonyl compounds: from transient intermediates to robust building
      blocks.
AB  - alpha-Borylcarbonyl species (C-bound boron enolates) are typically unstable due
      to their kinetic and thermodynamically favourable rearrangement to their O-bound
      isomers. Direct evidence of alpha-borylcarbonyl compounds is sparse despite the
      multitude of transformations in which they have been implicated as reactive
      intermediates. In recent years, a few examples have emerged of reactive alpha
      borylcarbonyl intermediates that can be observed using spectroscopic methods.
      Other reports have shown that certain compounds containing the alpha
      borylcarbonyl motif can be isolated under ambient conditions. Installation of
      electron-rich, tetracoordinate sp(3)-boron centers is a particularly viable
      strategy to improve the stability of alpha-borylcarbonyl systems as it imposes a
      barrier to the otherwise rapid 1,3-boron shift from carbon to oxygen. Among
      stable alpha-borylcarbonyl compounds, alpha-boryl aldehydes, equipped with a
      tetracoordinated N-methyliminodiacetyl (MIDA) boryl group, have been demonstrated
      to be versatile building blocks in the synthesis of a wide range of
      functionalized organoboron compounds. 

PMID- 24941219
TI  - Survival of adult generated hippocampal neurons is altered in circadian
      arrhythmic mice.
AB  - The subgranular zone of the hippocampal formation gives rise to new neurons that
      populate the dentate gyrus throughout life. Cells in the hippocampus exhibit
      rhythmic clock gene expression and the circadian clock is known to regulate the
      cycle of cell division in other areas of the body. These facts suggest that the
      circadian clock may regulate adult neurogenesis in the hippocampus as well. In
      the present study, neurogenesis in the hippocampal subgranular zone was examined
      in arrhythmic Bmal1 knockout (-KO) mice and their rhythmic heterozygous and
      wildtype littermates. Proliferation and survival of newly generated subgranular
      zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a
      measure of cell death) and hippocampal volume were examined in cresyl violet
      stained sections. There was no significant difference in cellular proliferation
      between any of the groups, yet survival of proliferating cells, 6 weeks after the
      bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals.
      The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet
      hippocampal volume remained the same across genotypes. These findings suggest
      that while a functional circadian clock is not necessary for normal proliferation
      of neuronal precursor cells, the normal pruning of newly generated neurons in the
      hippocampus may require a functional circadian clock. 

PMID- 24941222
TI  - Abstracts of the 2014 NATA Annual Meeting & Clinical Symposia, June 26-28, 2014,
      Indianapolis, Indiana.

PMID- 24941220
TI  - Glycoform analysis of recombinant and human immunodeficiency virus envelope
      protein gp120 via higher energy collisional dissociation and spectral-aligning
      strategy.
AB  - Envelope protein gp120 of human immunodeficiency virus (HIV) is armored with a
      dense glycan shield, which plays critical roles in envelope folding, immune
      evasion, infectivity, and immunogenicity. Site-specific glycosylation profiling
      of recombinant gp120 is very challenging. Therefore, glycoproteomic analysis of
      native viral gp120 is still formidable to date. This challenge promoted us to
      employ a Q-Exactive mass spectrometer to identify low abundant glycopeptides from
      virion-associated gp120. To search the HCD-MS data for glycopeptides, a novel
      spectral-aligning strategy was developed. This strategy depends on the
      observation that glycopeptides and the corresponding deglycosylated peptides
      share very similar MS/MS pattern in terms of b- and y-ions that do not contain
      the site of glycosylation. Moreover, glycopeptides with an identical peptide
      backbone show nearly resembling spectra regardless of the attached glycan
      structures. For the recombinant gp120, this "copy-paste" spectral pattern of
      glycopeptides facilitated identification of 2224 spectra using only 18 spectral
      templates, and after precursor mass correction, 1268 (57%) spectra were assigned
      to 460 unique glycopeptides accommodating 19 N-linked and one O-linked
      glycosylation sites (glycosites). Strikingly, we were able to observe five N- and
      one O-linked glycosites in native gp120. We further revealed that except for
      Asn276 in the C2 region, glycans were processed to contain both high mannose and
      hybrid/complex glycans; an additional four N-linked glycosites were decorated
      with high mannose type. Core 1 O-linked glycan Gal1GalNAc1 was seen for the O
      linked glycosite at Thr499. This direct observation of site-specific
      glycosylation of virion-derived gp120 has implications in HIV glycobiology and
      vaccine design. 

PMID- 24941223
TI  - Subcutaneous hyalohyphomycosis caused by Fusarium in a kidney transplant
      recipient.
AB  - Fusarium is a filamentous opportunistic pathogenic fungus responsible for
      superficial as well as invasive infection in immunocompromized hosts. Net state
      of immunosuppression and cytomegalovirus (CMV) infection appear to predispose to
      this disease which is life-threatening when disseminated. Though infections with
      Fusarium have been widely described in hematological malignancies and
      hematopoietic stem cell transplant cases, they have been reported to be rare in
      solid organ transplant recipients, are often localized and carry a favorable
      prognosis. We here describe a rare case of subcutaneous non-invasive infection
      with Fusarium in a renal allograft recipient two and half years after
      transplantation. Patient had a previous history of CMV infection along with
      multiple other recurrent co-infections. Diagnosis was based on culture of tissue
      specimens yielding Fusarium species. The infection had a protracted course with
      persistence of lesions after treatment with voriconazole alone, requiring a
      combination of complete surgical excision and therapy with the anti-fungal drug.

PMID- 24941226
TI  - Iridium-catalyzed annulation of salicylimines with 1,3-dienes.
AB  - Iridium-catalyzed annulation of salicylimines with 1,3-dienes gave high yields of
      the corresponding 4-aminochromanes with high stereoselectivity. The use of a
      chiral diene ligand enabled the asymmetric reaction to give 4-aminochromanes with
      high enantioselectivity. 

PMID- 24941228
TI  - Engineered coiled-coil protein microfibers.
AB  - The fabrication of de novo proteins able to self-assemble on the nano- to meso
      length scales is critical in the development of protein-based biomaterials in
      nanotechnology and medicine. Here we report the design and characterization of a
      protein engineered coiled-coil that not only assembles into microfibers, but also
      can bind hydrophobic small molecules. Under ambient conditions, the protein forms
      fibers with nanoscale structure possessing large aspect ratios formed by bundles
      of alpha-helical homopentameric assemblies, which further assemble into mesoscale
      fibers in the presence of curcumin through aggregation. Surprisingly, these
      biosynthesized fibers are able to form in conditions of remarkably low
      concentrations. Unlike previously designed coiled-coil fibers, these engineered
      protein microfibers can bind the small molecule curcumin throughout the assembly,
      serving as a depot for encapsulation and delivery of other chemical agents within
      protein-based 3D microenvironments. 

PMID- 24941225
TI  - Genetic variations affecting serum carcinoembryonic antigen levels and status of
      regional lymph nodes in patients with sporadic colorectal cancer from Southern
      China.
AB  - BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of
      disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal
      cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy
      and CRC population remains unclear. Thus we investigated the genetic markers
      associated with elevated serum sCEA level in these two populations and its
      clinical implications. METHODS AND FINDINGS: Genome-wide association study (GWAS)
      was conducted in a cohort study with 4,346 healthy male adults using the Illumina
      Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated
      in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated
      in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated
      sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph
      metastasis in the CRC patients. The preoperative sCEA level was a risk factor for
      tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005~1.843, P =
      0.006). It was also one of the risk factors for regional lymph node metastasis
      (OR = 2.266, 95% CI: 1.196~4.293, P = 0.012). The sCEA level in rs1047781-T
      carriers was higher than that in the A carriers in CRC patients without lymph
      node metastasis (P = 0.006). The regional lymph node metastasis in patients with
      homozygote AA of rs8176746 was more common than that in the heterozygote AG
      carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a
      worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS:
      We found candidate SNPs associated with elevated sCEA levels in both healthy
      males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus
      for recurrence of CRC in a population from Southern China.

PMID- 24941229
TI  - Dynamic structure of NGF and proNGF complexed with p75NTR: pro-peptide effect.
AB  - Crystallographic structures of NGF/p75NTR and proNGF/p75NTR were previously
      obtained in 2:1 and 2:2 stoichiometries, respectively. However, evidence shows
      that both stoichiometries can occur for mature neurotrophins and pro
      neurotrophins. We used Molecular Dynamics (MD) simulations to examine the
      energetic and structural characteristics of these two complete systems as well as
      the uncomplexed forms of NGF and understand how these could translate in a new
      view of different biological outcomes. Here, we show that one chain at the 2:2
      proNGF complex seems to be preferentially lost creating a 2:1 structure able to
      interact with sortilin. We also demonstrated that the structure of the
      neurotrophin dimers is not pre-established and suffers large structural
      modifications upon p75NTR binding. Moreover, our data suggests an elegant
      explanation for the dual role of NGF in neuronal cell death and survival, where
      different stoichiometries induce conformational changes that might be the basis
      for the different biological outcomes observed with the mature and proforms of
      neurotrophins. 

PMID- 24941230
TI  - Dosimetric variability of the rats' exposure to electromagnetic pulses.
AB  - Rats' exposure to electromagnetic pulses (EMPs) has been conducted using an EMP
      simulator for various biological endpoints. In contrast, information about the
      EMP energy distribution and its variability in rats is lacking. EMPs are signals
      with spectrum concentrating in several hundred MHz, leading to EM absorption
      patterns different from those obtained at high frequencies. In this study, two
      anatomical models of rats (a male and a female) were reconstructed from magnetic
      resonance imaging. The models had the same posture as in the exposure
      experiments. Realistic EMPs were acquired directly from the EMP simulator and
      applied to the simulations. The interaction of the EMP with the rat was analyzed
      through the finite-difference time-domain method. Two approaches were utilized to
      calculate the energy absorption at the tissue and whole-body levels. Dosimetric
      variability due to incident directions, polarizations, exposure signals
      simplification, and rat separation was evaluated in this study. The variability
      result differed substantially from that of the non-constrained rats' exposure
      experiments. The result sensitivity to frequency and amplitude was discussed as
      well. The work can be used as a basis to determine the uncertainty and to
      formulate a standard experimental protocol for this type of experiment. 

PMID- 24941231
TI  - Chemical investigation of Cyperus distans L. and inhibitory activity of
      scabequinone in seed germination and seedling growth bioassays.
AB  - Chemical investigation of the rhizomes of Cyperus distans (Cyperaceae) led to the
      identification of alpha-ciperone, cyperotundone and scabequinone, besides other
      common constituents. Complete assignment of the (13)C NMR data of scabequinone is
      being published for the first time. The inhibitory effects of C. distans extracts
      and scabequinone on the seed germination and seedling growth of Mimosa pudica,
      Senna obtusifolia and Pueraria phaseoloides were evaluated. Seed germination
      inhibition bioassay revealed that S. obtusifolia (52-53%) was more sensitive to
      the hexane and the methanol extracts at 1% than M. pudica (0-10%). Scabequinone
      at 250 mg L-1 displayed seed germination inhibitions more than 50% and radicle
      growth reduction of more than 35% of the test species S. obtusifolia and P.
      phaseoloides, while the hypocotyl growth of M. pudica was significantly affected
      (>50%) by the quinone at the same concentration. These results demonstrate that
      scabequinone contributes to the overall inhibitory activities of C. distans.

PMID- 24941233
TI  - Giant chorioangioma treated in utero via laser of feeding vessels with subsequent
      development of multifocal infantile hemangiomas.
AB  - We report a case of a giant placental chorioangioma (15.6 cm diameter)
      complicated by polyhydramnios and severe fetal heart failure. Fetoscopic laser
      occlusion of a dominant feeding vessel was performed at 29 weeks' gestation and
      partial devascularization was achieved. In the 33rd week of the pregnancy, the
      decision was made to preemptively deliver the fetus due to persistent signs of
      fetal cardiac failure. After birth, the infant developed multifocal infantile
      hemangiomas with extracutaneous involvement. We posit that the development of
      infantile hemangiomas may be linked to the presence of the large chorioangioma.
      Further study is required to ascertain if fetal treatment of the chorioangioma
      may have been an exacerbating factor. 

PMID- 24941232
TI  - Whole brain expression of bipolar disorder associated genes: structural and
      genetic analyses.
AB  - Studies of bipolar disorder (BD) suggest a genetic basis of the illness that
      alters brain function and morphology. In recent years, a number of genetic
      variants associated with BD have been identified. However, little is known about
      the associated genes, or brain circuits that rely upon their function. Using an
      anatomically comprehensive survey of the human transcriptome (The Allen Brain
      Atlas), we mapped the expression of 58 genes with suspected involvement in BD
      based upon their relationship to SNPs identified in genome wide association
      studies (GWAS). We then conducted a meta-analysis of structural MRI studies to
      identify brain regions that are abnormal in BD. Of 58 BD associated genes, 22 had
      anatomically distinct expression patterns that could be categorized into one of
      three clusters (C1-C3). Brain regions with the highest and lowest expression of
      these genes did not overlap strongly with anatomical sites identified as abnormal
      by structural MRI except in the parahippocampal gyrus, the inferior/superior
      temporal gyrus and the cerebellar vermis, regions where overlap was significant.
      Using the 22 genes in C1-C3 as reference points, additional genes with correlated
      expression patterns were identified and organized into sets based on similarity.
      Further analysis revealed that five of these gene sets were significantly
      associated with BD, suggesting that anatomical expression profile is correlated
      with genetic susceptibility to BD, particularly for genes in C2. Our data suggest
      that expression profiles of BD-associated genes do not explain the majority of
      structural abnormalities observed in BD, but may be useful in identifying new
      candidate genes. Our results highlight the complex neuroanatomical basis of BD,
      and reinforce illness models that emphasize impaired brain connectivity.

PMID- 24941234
TI  - Which is currently the best strategy for treatment of SFA in-stent restenosis?
AB  - Stents have been created to prevent vessel recoil after percutaneous transluminal
      angioplasty (PTA). Despite the evolution in stent design, intimal hyperplasia and
      stent fractures and the resulting in-stent restenosis (ISR) still occur.
      Different strategies to treat ISR have been described with variable results in
      patency rates in the short and the long-term. PTA only in the treatment of ISR
      showed high procedural success, but the mid and long-term patency rates were very
      disappointing. Atherectomy devices have showed same insufficient results. If
      stent fracture is the cause of the ISR, the fracture has to be overstent. The
      best two options are covered stents and drug eluting stents (DES). Drug eluting
      devices like DES and drug eluting balloons (DEBs) showed promising results, with
      patency rates up to over 90% after one year. DEBs have the advantage of leaving
      nothing behind. Combined treatment of ISR with atherectomy and DEB has a similar
      good result. Endovascular brachytherapy showed high patency rates after one year
      but this technique is limited due to the time-consuming nature of the procedure,
      complex radiation safety measurements, and staffing requirements. Overall drug
      eluting devices are emerging as the best treatment of SFA ISR with patency rates
      over 90% after 2 years. 

PMID- 24941235
TI  - Prime time for drug eluting balloons in SFA interventions?
AB  - Peripheral arterial disease most commonly affects the femoropopliteal segment.
      Despite enormous improvements in device and treatment technology the long-term
      patency rate and clinical benefit of endovascular treatment in the respective
      vascular bed is not satisfying. Drug coated balloon technology as a treatment
      option in femoropopliteal disease has shown encouraging results in first-in-man
      trials, which have now been proven in large randomized controlled trials. 

PMID- 24941236
TI  - Current endovascular management of acute type B aortic dissection - whom should
      we treat and when?
AB  - Aortic dissection is the most common of the acute aortic syndromes, once
      initiated, intimal disruption can propagate in an anterograde or retrograde
      fashion, and the resulting false lumen may compress the ostia of aortic branches
      or cause aortic expansion and eventual rupture. Acute complicated type B
      dissection most often requires immediate interventional treatment, whereas
      uncomplicated dissection has classically been managed with medical therapy alone.
      The first line management of complicated acute and aneurysmal chronic type B
      dissections has shifted toward minimally invasive endovascular treatment. To give
      an overview of the contemporary management of acute type B dissection, clinical
      manifestations, aims of management, and therapeutic options are discussed in the
      context deciding which patients require intervention and when. 

PMID- 24941237
TI  - Optimising pre- and postoperative imaging for thoracic aortic pathology.
AB  - Thoracic aortic pathology carries significant morbidity and mortality, which
      requires prompt and accurate clinical and radiological evaluation. Advances in
      imaging technologies have improved our knowledge of the mechanisms of growth and
      rupture and our understanding of endovascular repair. Computed tomography has
      become a crucial component in this process, replacing catheter-based angiography
      as the most commonly used pre- and postoperative imaging modality for the
      thoracic aorta. Functional imaging methods such as magnetic resonance and
      echocardiography are evolving and are able to provide the clinically relevant
      anatomic, haemodynamic and biomechanical information that is necessary for
      accurate diagnosis, risk stratification and selection of the appropriate
      treatment for an individual patient. The availability of advanced image
      acquisition expertise and equipment is spreading to a growing number of
      institutions worldwide and will greatly enhance existing imaging strategies for
      patients with thoracic aortic pathology. 

PMID- 24941238
TI  - Results of reinterventions for failed endovascular aortic repair: a single-center
      experience.
AB  - AIM: The aim of this paper was to review technical success and clinical outcome
      of reinterventions to treat complications after endovascular abdominal aortic
      aneurysm (AAA) repair (EVAR) in a tertiary vascular center. METHODS: The study
      enrolled 107 patients treated for post-EVAR complications between January 2005
      and March 2014. Details of reinterventions, technical success, and midterm
      clinical outcome were analyzed for reinterventions. Radiologic follow-up after
      reinterventions was performed by computed tomography scans and duplex
      ultrasonography. RESULTS: Indications for reinterventions in the 107 patients
      were predominantly endoleaks type Ia, Ib, II, and III (55.1%). Endograft
      obstructions were observed in 39 patients (36.4%). The initial technical success
      rate for the 107 reinterventions was 93.5% (N.=100). Median follow-up
      postreintervention was 20 months (range, 1-107 months). During follow-up, 34 of
      107 patients (31.8%) needed at least one renewed reintervention. Kaplan-Meier
      analysis of overall survival after the primary reinterventions was 85% at 1 year,
      and 78% at 3 years of follow-up. AAA/EVAR-associated mortality was 4% at 3 years.
      Kaplan-Meier survival estimation of freedom of recurrence was 88% at 1 year post
      reintervention and 78% at 3 years. Renewed reintervention-free survival dropped
      to 78% at 1 year and 58% at 3 years. CONCLUSION: In this series of patients, the
      technical success rate of reinterventions to treat post-EVAR complications was
      high. During a median follow-up of 20 months, AAA-associated mortality is low,
      but the need for renewed (endovascular) reinterventions is substantial.

PMID- 24941239
TI  - Pedal and plantar loop angioplasty: technique and results.
AB  - Endovascular and subintimal approaches fails in obtaining a below-the-knee
      recanalization in 10-40% of cases, even in high-volume and expertise centers. The
      presence of long calcified occlusions, characterized by a complex anatomy, often
      necessitate the use of alternative techniques in order to obtain a direct blood
      flow to the foot arteries. Recanalization using pedal and plantar loop
      angioplasty could improve outcomes in the presence of a communication between the
      dorsal and plantar arch of the foot, if conventional techniques are not
      effective. 

PMID- 24941241
TI  - Value of covered stents to improve patency of long-segment SFA revascularization.
AB  - Endovascular treatment has become first-line approach for revascularization of
      long and complex femoropopliteal lesions in many centers. This development urges
      the need for endovascular approaches with a sustainable success in terms of
      patency. In several recently published trials the Viabahn(r) endoprosthesis by
      Gore (W.L. Gore Inc, Flagstaff, AZ, USA) has shown promising patency rates
      comparable or even better than traditional surgical bypass procedures with
      prosthetic material. 

PMID- 24941240
TI  - Hybrid revascularization of complex multilevel disease: a paradigm shift in
      critical limb ischemia treatment.
AB  - Critical limb ischemia frequently occurs on a background of extensive co
      morbidities and carries a poor prognosis which requires urgent management.
      Disease severity and patient comorbidity influence the initial choice of
      management which according to traditional paradigms, is a choice between open or
      endovascular repair. Over the last decade hybrid intervention, which is the
      planned combined use of both open and endovascular techniques, has increasingly
      been used to tackle multilevel disease. In this review we look at the techniques
      and results of hybrid surgery. This technique is ideal for multilevel lesions, as
      it is minimally invasive, allows prompt limb revascularization as opposed to the
      delays inherent in staged procedures and it appears to be more convenient to
      patients. It also leads to reduced length of hospital stay and reduces overall
      cost. Most importantly it offers an alternative to open revascularization in
      medically high risk patients. The success and popularity of hybrid interventions
      has been underpinned by advances in stent and balloon technology and the advent
      of the hybrid operating theatre which has allowed multiple techniques to be used
      simultaneously. Iliac angioplasty and stenting is now the first line of treatment
      for TASC C/D iliac lesions with good technical success and long-term patency. In
      patients who also have common femoral disease, endarterectomy can be combined
      with iliac stenting and this has now almost replaced open bypass. Most series for
      a variety of hybrid procedures report good limb salvage rates, with morbidity and
      mortality data considered equal to or better than open bypass procedures. Careful
      patient selection and detailed preoperative planning are essential to achieve
      these excellent results. Studies have reported on prospective series or
      retrospective analysis for various hybrid techniques, including non randomized
      trials comparing hybrid and open surgical treatment. Ideally, a randomized
      controlled trial comparing open and hybrid treatment is needed to minimize
      confounding variables. 

PMID- 24941242
TI  - Drug-coated balloons and drug-eluting stents: clinical effectiveness revisited.
AB  - Critical limb ischemia (CLI) is a common and devastating manifestation of
      peripheral arterial disease leading to ischemic rest pain, ulcerations, gangrene
      and tissue loss. Thus advanced endovascular techniques have been developed in
      order to achieve higher success rate, such as retrograde recanalisation and drug
      eluting devices. However, the correlation between patency of the vessels and
      clinical outcome (limb salvage, ulcer healing, Rutherford class improvement) is
      still debated. We reviewed the most recent trials and studies investigating the
      clinical effectiveness of drug eluting stents and balloons for the treatment of
      CLI. 

PMID- 24941243
TI  - Angiogenic cell therapy for critical limb ischemia: an update on concepts and
      trials.
AB  - Therapeutic neovascularization is a novel approach used to salvage critically
      ischemic limbs that are not amenable to conventional treatments. Initial efforts
      were based on single injections of angiogenic factors but there is now a
      realization that delivering angiogenic cells is more likely to achieve effective
      revascularization. Clinical studies to date have mostly used mixtures of
      mononuclear cells harvested from the bone marrow or peripheral blood. The modest
      results achieved with these cells, only a proportion of which are angiogenic, has
      stimulated a search for more potent cell types. Preclinical studies have
      identified several candidates, including adipose derived, embryonic and induced
      pluripotent stem cells. This review provides an update on the current status of
      angiogenic cell therapy for the ischemic limb and outlines efforts aimed at
      enhancing the clinical efficacy of treatments. 

PMID- 24941244
TI  - Latest developments in SFA management.

PMID- 24941245
TI  - Enhancement of heterogeneous assays using fluorescent magnetic liposomes.
AB  - Interactions between solution phase analytes and surface immobilized
      biorecognition elements in heterogeneous binding assay formats, such as enzyme
      linked immunosorbent assays (ELISAs), are often hindered by mass transfer
      limitations. In order to improve detection limits and decrease assay times, an
      applied magnetic field can be used to promote target binding events if the
      species used for signal generation is rendered magnetic. Here, a ferromagnetic
      metal oxide-oleic acid complex was incorporated into the lipid bilayer of
      fluorescent dye-encapsulating liposomes, allowing for their influence under a
      magnetic field while maintaining their high interior encapsulation volume for
      signaling molecules. In a high-throughput sandwich-hybridization assay, these DNA
      tagged liposomes yielded enhanced sensitivity, in addition to reduced assay times
      and reagent concentrations, when used with an underlying magnet. These magnetic
      signaling reagents offer superior performance and adaptability to standard assay
      formats. 

PMID- 24941247
TI  - Primarily oseltamivir-resistant influenza A (H1N1pdm09) virus evolving into a
      multidrug-resistant virus carrying H275Y and I223R neuraminidase substitutions.
AB  - Antiviral susceptibility testing and reporting of viruses carrying amino acid
      substitutions conferring antiviral drug resistance is essential to assess the
      spread and clinical impact of these viruses. Here, we report on a patient who was
      infected with a primarily oseltamivir-resistant influenza A (H1N1pdm09) virus
      following allogeneic stem cell transplantation and rituximab treatment. Under
      prolonged virus replication and zanamivir therapy the neuraminidase amino acid
      substitutions H275Y and I223R were detected conferring high-level resistance to
      oseltamivir and cross-resistance to zanamivir. The emergence of these amino acid
      changes has been reported rarely worldwide and has been associated with fatal
      clinical outcomes. The patient survived the influenza infection after 170 days of
      follow-up. 

PMID- 24941246
TI  - Assessment of cytochrome C oxidase dysfunction in the substantia nigra/ventral
      tegmental area in schizophrenia.
AB  - Perturbations in metabolism are a well-documented but complex facet of
      schizophrenia pathology. Optimal cellular performance requires the proper
      functioning of the electron transport chain, which is constituted by four enzymes
      located within the inner membrane of mitochondria. These enzymes create a proton
      gradient that is used to power the enzyme ATP synthase, producing ATP, which is
      crucial for the maintenance of cellular functioning. Anomalies in a single enzyme
      of the electron transport chain are sufficient to cause disruption of cellular
      metabolism. The last of these complexes is the cytochrome c oxidase (COX) enzyme,
      which is composed of thirteen different subunits. COX is a major site for
      oxidative phosphorylation, and anomalies in this enzyme are one of the most
      frequent causes of mitochondrial pathology. The objective of the present report
      was to assess if metabolic anomalies linked to COX dysfunction may contribute to
      substantia nigra/ventral tegmental area (SN/VTA) pathology in schizophrenia. We
      tested COX activity in postmortem SN/VTA from schizophrenia and non-psychiatric
      controls. We also tested the protein expression of key subunits for the assembly
      and activity of the enzyme, and the effect of antipsychotic medication on subunit
      expression. COX activity was not significantly different between schizophrenia
      and non-psychiatric controls. However, we found significant decreases in the
      expression of subunits II and IV-I of COX in schizophrenia. Interestingly, these
      decreases were observed in samples containing the entire rostro-caudal extent of
      the SN/VTA, while no significant differences were observed for samples containing
      only mid-caudal regions of the SN/VTA. Finally, rats chronically treated with
      antipsychotic drugs did not show significant changes in COX subunit expression.
      These findings suggest that COX subunit expression may be compromised in specific
      sub-regions of the SN/VTA (i.e. rostral regions), which may lead to a faulty
      assembly of the enzyme and a greater vulnerability to metabolic insult. 

PMID- 24941248
TI  - Effect of an artificial silk elastin-like protein on the migration and collagen
      production of mouse fibroblasts.
AB  - A silk elastin-like protein (SELP) is an artificial compound composing silk
      fibroin-like and elastin-like tandem repeats. The objective of this study is to
      evaluate the SELP effect on the migration, proliferation, and proteins production
      of L929 mouse fibroblasts. Upon culturing with different concentrations of SELP,
      the cells migration and their collagen production significantly enhanced in the
      SELP concentrations from 10(-3) to 10 MUg/ml. However, irrespective of the SELP
      concentration, no difference in the production of fibronectin, basic fibroblast
      growth factor (bFGF), vascular endothelial growth factor (VEGF), and stromal cell
      derived factor 1alpha (SDF-1alpha) was observed. When the migration of mouse
      peritoneal macrophages by SELP was evaluated, significant enhancement of
      macrophages migration was observed in any concentration. It is concluded that the
      SELP has a potential to promote the migration of fibroblasts and macrophages, and
      the fibroblast collagen production.

PMID- 24941250
TI  - Proteomic analysis of embryogenesis and the acquisition of seed dormancy in
      Norway maple (Acer platanoides L.).
AB  - The proteome of zygotic embryos of Acer platanoides L. was analyzed via high
      resolution 2D-SDS-PAGE and MS/MS in order to: (1) identify significant
      physiological processes associated with embryo development; and (2) identify
      changes in the proteome of the embryo associated with the acquisition of seed
      dormancy. Seventeen spots were identified as associated with morphogenesis at 10
      to 13 weeks after flowering (WAF). Thirty-three spots were associated with
      maturation of the embryo at 14 to 22 WAF. The greatest changes in protein
      abundance occurred at 22 WAF, when seeds become fully mature. Overall, the stage
      of morphogenesis was characterized by changes in the abundance of proteins
      (tubulins and actin) associated with the growth and development of the embryo.
      Enzymes related to energy supply were especially elevated, most likely due to the
      energy demand associated with rapid growth and cell division. The stage of
      maturation is crucial to the establishment of seed dormancy and is associated
      with a higher abundance of proteins involved in genetic information processing,
      energy and carbon metabolism and cellular and antioxidant processes. Results
      indicated that a glycine-rich RNA-binding protein and proteasome proteins may be
      directly involved in dormancy acquisition control, and future studies are
      warranted to verify this association. 

PMID- 24941251
TI  - Activation of mGluR5 attenuates NMDA-induced neurotoxicity through disruption of
      the NMDAR-PSD-95 complex and preservation of mitochondrial function in
      differentiated PC12 cells.
AB  - Glutamate-mediated toxicity is implicated in various neuropathologic conditions,
      and activation of ionotropic and metabotropic glutamate receptors is considered
      to be the most important mechanism. It has been reported that pharmacological
      saturation of metabotropic glutamate receptors (mGluRs) can facilitate N-methyl-D
      aspartate receptor (NMDAR) related signaling cascades, but the mechanism leading
      to mGluR-NMDAR interactions in excitotoxic neuronal injury has remained
      unidentified. In the present study, we investigated the role of mGluR5 in the
      regulation of N-methyl-D-aspartate (NMDA)-induced excitotoxicity in
      differentiated PC12 cells. We found that activation of mGluR5 with the specific
      agonist R,S-2-chloro-5-hydroxyphenylglycine (CHPG) increased cell viability and
      inhibited lactate dehydrogenase (LDH) release in a dose-dependent manner. CHPG
      also inhibited an increase in the Bax/Bcl-2 ratio, attenuated cleavage of caspase
      9 and caspase-3, and reduced apoptotic cell death after NMDA treatment. The NMDA
      induced mitochondrial dysfunction, as indicated by mitochondrial reactive oxygen
      species (ROS) generation, collapse of mitochondrial membrane potential (MMP), and
      cytochrome c release, was also partly prevented by CHPG treatment. Furthermore,
      CHPG blocked the NMDA-induced interaction of NMDAR with postsynaptic density
      protein-95 (PSD-95), but had no effects on intracellular calcium concentrations.
      All these results indicated that activation of mGluR5 protects differentiated
      PC12 cells from NMDA-induced neuronal excitotoxicity by disrupting NMDAR-PSD-95
      interaction, which might be an ideal target for investigating therapeutic
      strategies in various neurological diseases where excitotoxicity may contribute
      to their pathology.

PMID- 24941252
TI  - Synthesis and antioxidant activity evaluation of new compounds from
      hydrazinecarbothioamide and 1,2,4-triazole class containing diarylsulfone and 2,4
      difluorophenyl moieties.
AB  - In the present investigation, new hydrazinecarbothioamides 4-6 were synthesized
      by reaction of 4-(4-X-phenylsulfonyl)benzoic acids hydrazides (X=H, Cl, Br) 1-3
      with 2,4-difluorophenyl isothiocyanate and further these were treated with sodium
      hydroxide to obtain 1,2,4-triazole-3-thione derivatives 7-9. The reaction of 7-9
      with alpha-halogenated ketones, in basic media, afforded new S-alkylated
      derivatives 10-15. The structures of the synthesized compounds have been
      established on the basis of 1H-NMR, 13C-NMR, IR, mass spectral studies and
      elemental analysis. The antioxidant activity of all compounds has been screened.
      Hydrazinecarbothioamides 4-6 showed excellent antioxidant activity and 1,2,4
      triazole-3-thiones 7-9 showed good antioxidant activity using the DPPH method.

PMID- 24941253
TI  - The constituents of Michelia compressa var. formosana and their bioactivities.
AB  - Phytochemical investigation of the heartwood of Michelia compressa afforded forty
      four compounds, which were identified by comparison of experimental and
      literature analytical and spectroscopic data. Some compounds were evaluated for
      their anti-inflammatory and anticancer bioactivities. The result showed that
      soemerine (1) and cyathisterol (2) exhibited significant nitric oxide (NO)
      inhibition, with IC50 values of 8.5+/-0.3 and 9.6+/-0.5 ug/mL, respectively. In
      addition, liriodenine (3) and oliveroline (4) exhibited cytotoxicity to human
      nasopharyngeal carcinoma (NPC-TW01), non-small cell lung carcinoma (NCI-H226), T
      cell leukemia (Jurkat), renal carcinoma (A498), lung carcinoma (A549) and
      fibrosarcoma (HT1080) cell lines with IC50 values in the range of 15.7-3.68 MUM.

PMID- 24941256
TI  - Indoor air quality in green vs conventional multifamily low-income housing.
AB  - Indoor air quality is an important predictor of health, especially in low-income
      populations. It is unclear how recent trends in "green" building affect the
      indoor exposure profile. In two successive years, we conducted environmental
      sampling, home inspections, and health questionnaires with families in green and
      conventional (control) apartments in two public housing developments. A subset of
      participants was followed as they moved from conventional to green or
      conventional to conventional housing. We measured particulate matter less than
      2.5 MUm aerodynamic diameter (PM2.5), formaldehyde, nitrogen dioxide (NO2),
      nicotine, carbon dioxide (CO2), and air exchange rate (AER) over a seven-day
      sampling period coincident with survey administration. In multivariate models, we
      observed 57%, 65%, and 93% lower concentrations of PM2.5, NO2, and nicotine
      (respectively) in green vs control homes (p=0.032, p<0.001, p=0.003,
      respectively), as well as fewer reports of mold, pests, inadequate ventilation,
      and stuffiness. Differences in formaldehyde and CO2 were not statistically
      significant. AER was marginally lower in green buildings (p=0.109). Participants
      in green homes experienced 47% fewer sick building syndrome symptoms (p<0.010).
      We observed significant decreases in multiple indoor exposures and improved
      health outcomes among participants who moved into green housing, suggesting
      multilevel housing interventions have the potential to improve long-term resident
      health.

PMID- 24941255
TI  - Poly(3-hydroxybutyrate)/ZnO bionanocomposites with improved mechanical, barrier
      and antibacterial properties.
AB  - Poly(3-hydroxybutyrate) (PHB)-based bionanocomposites incorporating different
      contents of ZnO nanoparticles were prepared via solution casting technique. The
      nanoparticles were dispersed within the biopolymer without the need for
      surfactants or coupling agents. The morphology, thermal, mechanical, barrier,
      migration and antibacterial properties of the nanocomposites were investigated.
      The nanoparticles acted as nucleating agents, increasing the crystallization
      temperature and the degree of crystallinity of the matrix, and as mass transport
      barriers, hindering the diffusion of volatiles generated during the decomposition
      process, leading to higher thermal stability. The Young's modulus, tensile and
      impact strength of the biopolymer were enhanced by up to 43%, 32% and 26%,
      respectively, due to the strong matrix-nanofiller interfacial adhesion attained
      via hydrogen bonding interactions, as revealed by the FT-IR spectra. Moreover,
      the nanocomposites exhibited reduced water uptake and superior gas and vapour
      barrier properties compared to neat PHB. They also showed antibacterial activity
      against both Gram-positive and Gram-negative bacteria, which was progressively
      improved upon increasing ZnO concentration. The migration levels of PHB/ZnO
      composites in both non-polar and polar simulants decreased with increasing
      nanoparticle content, and were well below the current legislative limits for food
      packaging materials. These biodegradable nanocomposites show great potential as
      an alternative to synthetic plastic packaging materials especially for use in
      food and beverage containers and disposable applications. 

PMID- 24941254
TI  - HSPC117 is regulated by epigenetic modification and is involved in the migration
      of JEG-3 cells.
AB  - The human hematopoietic stem/progenitor cell 117 (HSPC117) protein is an
      essential component of protein complexes and has been identified to be involved
      in many important functions. However, how this gene expression is regulated and
      whether the HSPC117 gene affects cell migration is still unknown. The aim of this
      study was to identify whether HSPC117 mRNA expression is regulated by epigenetic
      modification and whether HSPC117 expression level affects the expression of
      matrix metalloproteinase 2 (MMP 2), matrix metalloproteinase 14 (MMP 14), and
      tissue inhibitor of metalloproteinases 2 (TIMP 2), and further affects human
      placenta choriocarcinoma cell (JEG-3) migration speed. In our epigenetic
      modification experiment, JEG-3 cells were cultured in medium with the DNA
      methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC), the histone
      deacetylase (HDAC) inhibitor trichostatin A (TSA), or both inhibitors. Then, the
      HSPC117 mRNA and protein expressions were assessed using real-time quantitative
      PCR (qPCR) and Western blot assay. The results showed that, compared to the
      control, HSPC117 mRNA expression was increased by TSA or 5-aza-dC. The highest
      HSPC117 expression level was found after treatment with both 5-aza-dC and TSA.
      Further, in order to investigate the effect of HSPC117 on MMP 2, MMP 14, and TIMP
      2 mRNA expressions, pEGFP-C1-HSPC117 plasmids were transfected into JEG-3 cells
      to improve the expression of HSPC117 in the JEG-3 cells. Then, the mRNA
      expression levels of MMP 2, MMP 14, TIMP 2, and the speed of cell migration were
      assessed using the scratch wound assay. The results showed that over-expression
      of HSPC117 mRNA reduced MMP 2 and MMP 14 mRNA expression, while TIMP 2 mRNA
      expression was up-regulated. The scratch wound assay showed that the migration
      speed of JEG-3 cells was slower than the non-transfected group and the C1
      transfected group. All of these results indicate that HSPC117 mRNA expression is
      regulated by epigenetic modification; over-expression of HSPC117 decreases MMP 2
      and MMP 14 transcription, reduces cell migration speed, and increases TIMP 2
      transcription. 

PMID- 24941257
TI  - Correlation analysis of EV71 detection and case severity in hand, foot, and mouth
      disease in the Hunan Province of China.
AB  - An increase in the incidence of hand, foot and mouth disease (HFMD) cases has
      been observed in the Hunan province of mainland China since 2009 with a
      particularly higher level of severe cases in 2010-2012. Intestinal viruses of the
      picornaviridae family are responsible for the human syndrome associated with HFMD
      with enterovirus 71 (EV71) and Coxsackievirus A16 (Cox A16) being the most common
      causative strains. HFMD cases associated with EV71 are generally more severe with
      an increased association of morbidity and mortality. In this study, the etiology
      surveillance data of HFMD cases in Hunan province from March 2010 to October 2012
      were analyzed to determine if there is a statistically relevant linear
      correlation exists between the detection rate of EV71 in mild cases and the
      proportion of severe cases among all HFMD patients. As the cases progressed from
      mild to severe to fatal, the likelihood of EV71 detection increased (25.78%,
      52.20% and 84.18%, respectively). For all cases in the timeframe evaluated in
      this study, the presence of virus was detected in 63.21% of cases; among cases
      showing positivity for virus, EV71 infection accounted for 50.14%. These results
      provide evidence to support the observed higher morbidity and mortality
      associated with this outbreak and emphasizes the importance of early detection in
      order to implement necessary prevention measures to mitigate disease progression.

PMID- 24941258
TI  - The future of large old trees in urban landscapes.
AB  - Large old trees are disproportionate providers of structural elements (e.g.
      hollows, coarse woody debris), which are crucial habitat resources for many
      species. The decline of large old trees in modified landscapes is of global
      conservation concern. Once large old trees are removed, they are difficult to
      replace in the short term due to typically prolonged time periods needed for
      trees to mature (i.e. centuries). Few studies have investigated the decline of
      large old trees in urban landscapes. Using a simulation model, we predicted the
      future availability of native hollow-bearing trees (a surrogate for large old
      trees) in an expanding city in southeastern Australia. In urban greenspace, we
      predicted that the number of hollow-bearing trees is likely to decline by 87%
      over 300 years under existing management practices. Under a worst case scenario,
      hollow-bearing trees may be completely lost within 115 years. Conversely, we
      predicted that the number of hollow-bearing trees will likely remain stable in
      semi-natural nature reserves. Sensitivity analysis revealed that the number of
      hollow-bearing trees perpetuated in urban greenspace over the long term is most
      sensitive to the: (1) maximum standing life of trees; (2) number of regenerating
      seedlings ha(-1); and (3) rate of hollow formation. We tested the efficacy of
      alternative urban management strategies and found that the only way to arrest the
      decline of large old trees requires a collective management strategy that
      ensures: (1) trees remain standing for at least 40% longer than currently
      tolerated lifespans; (2) the number of seedlings established is increased by at
      least 60%; and (3) the formation of habitat structures provided by large old
      trees is accelerated by at least 30% (e.g. artificial structures) to compensate
      for short term deficits in habitat resources. Immediate implementation of these
      recommendations is needed to avert long term risk to urban biodiversity.

PMID- 24941259
TI  - Time pressure inhibits dynamic advantage in the classification of facial
      expressions of emotion.
AB  - Recent studies suggest an advantage in the recognition of dynamic over static
      facial expressions of emotion. Here, we explored the differences in the
      processing of static and dynamic faces under condition of time pressure. A group
      of 18 participants classified static and dynamic facial expressions (angry,
      happy, and neutral). In order to increase the goal-directed attention,
      instructions emphasized speed and announced time pressure in the interval for the
      response (maximal 600 ms). Participants responded faster and more accurately in
      the static than in the dynamic condition. Event-related potentials (ERPs) showed
      larger amplitude of the P1 (90-130 ms) and LPC (300-600 ms) components for
      dynamic relative to static stimuli, indicating enhanced early visual processing
      and emotional attention. On the other hand, the N170 was more negative in static
      relative to dynamic faces, suggesting better structural encoding for static faces
      under time pressure. The present study shows some advantages in the processing of
      static over dynamic facial expressions of emotion when the top-down (goal-driven)
      attention is strengthened. 

PMID- 24941260
TI  - ClinicalCodes: an online clinical codes repository to improve the validity and
      reproducibility of research using electronic medical records.
AB  - Lists of clinical codes are the foundation for research undertaken using
      electronic medical records (EMRs). If clinical code lists are not available,
      reviewers are unable to determine the validity of research, full study
      replication is impossible, researchers are unable to make effective comparisons
      between studies, and the construction of new code lists is subject to much
      duplication of effort. Despite this, the publication of clinical codes is rarely
      if ever a requirement for obtaining grants, validating protocols, or publishing
      research. In a representative sample of 450 EMR primary research articles indexed
      on PubMed, we found that only 19 (5.1%) were accompanied by a full set of
      published clinical codes and 32 (8.6%) stated that code lists were available on
      request. To help address these problems, we have built an online repository where
      researchers using EMRs can upload and download lists of clinical codes. The
      repository will enable clinical researchers to better validate EMR studies, build
      on previous code lists and compare disease definitions across studies. It will
      also assist health informaticians in replicating database studies, tracking
      changes in disease definitions or clinical coding practice through time and
      sharing clinical code information across platforms and data sources as research
      objects. 

PMID- 24941261
TI  - Assessment of sleep-related disorders in children with sickle cell disease.
AB  - Sleep-related disorders (SRDs) are common in sickle cell disease, however,
      identification may be time-consuming. Simultaneous survey of multiple SRDs
      utilizing a simplified instrument would facilitate screening. A simplified
      questionnaire investigating SRDs [sleep-disordered breathing (SDB), restless legs
      syndrome (RLS), insomnia, parasomnias, and daytime effects of disrupted sleep]
      was administered to 2-18-year-old children with sickle cell disease. One hundred
      participants completed this 5-7 minute survey without difficulties: 54 awoke
      unrefreshed, 41 had short-term insomnia, 30 had sleep-maintenance insomnia, 21
      had chronic sleep-onset insomnia, 54 had chronic habitual snoring and 11 met the
      criteria for RLS. Sleep-maintenance insomnia was associated with increased body
      mass index (BMI) (p = 0.001), and chronic sleep-onset insomnia was associated
      with higher hemoglobin (Hb) levels (p = 0.04). Survey-reported symptoms of SRDs
      were significantly higher than that reported in the general pediatric population.
      A fast and simplified SRD survey is feasible and suggests a high prevalence of
      SRDs in children with sickle cell disease.

PMID- 24941263
TI  - Plausible authentication of manuka honey and related products by measuring
      leptosperin with methyl syringate.
AB  - Manuka honey, obtained from Leptospermum scoparium flowers in New Zealand, has
      strong antibacterial properties. In this study, plausible authentication of the
      manuka honey was inspected by measuring leptosperin, methyl syringate 4-O-beta-D
      gentiobiose, along with methyl syringate. Despite a gradual decrease in methyl
      syringate content over 30 days at 50  degrees C, even at moderate 37  degrees C,
      leptosperin remained stable. A considerable correlation between nonperoxide
      antibacterial activity and leptosperin content was observed in 20 certified
      manuka honey samples. Leptosperin and methyl syringate in manuka honey and
      related products were analyzed using HPLC connected with mass spectrometry. One
      noncertified brand displayed significant variations in the leptosperin and methyl
      syringate contents between two samples obtained from different regions.
      Therefore, certification is clearly required to protect consumers from disguised
      and/or low-quality honey. Because leptosperin is stable during storage and
      specific to manuka honey, its measurement may be applicable for manuka honey
      authentication. 

PMID- 24941264
TI  - Ulcer and bleeding complications and their relationship with dyspeptic symptoms
      in NSAIDs users: a transversal multicenter study.
AB  - OBJECTIVES: To evaluate the prevalence of lesions and digestive complications
      secondary to the use of non-steroidal anti-inflammatory drugs (NSAIDs), the
      clinical profile seen for digestive complaints and the relation with the
      endoscopic findings. METHODS: Prospective, multicentric, open study, evaluating
      consecutively 1231 patients, divided as follows: group I - NSAID and group II -
      non-NSAID. All patients answered questionnaire to evaluate the onset, the type of
      clinical complaint, the use of medication and possible complications associated
      to digestive bleeding. RESULTS. A total of 1213 patients were evaluated. Among
      them, 65% were female and 13.1% were smokers; 15.6% mentioned they ingested
      alcoholic beverages. The main signs and symptoms reported were epigastralgy and
      pyrosis (67% and 62%, respectively). The upper gastrointestinal (UGI) endoscopy
      was normal in 3.9% in group I and in 10.7% in group II (p < 0.001). Patient who
      do not use NSAID will be 2.5 times more likely to have normal UGI endoscopy (p =
      0.001). The presence of erosive or ulcer lesions in the stomach and duodenum was
      more frequent in group I. The incidence of lesions in the stomach when compared
      to the duodenum is observed (erosions: 49.12% vs. 13.60%, p = 0.001; ulcers:
      14.04% vs. 11.84%, p = 0.05). The risk of digestive bleeding is 12 times higher
      (6.14% vs. 0.51%) in those who used NSAIDs, and the stomach is the site in which
      bleeding occurs more frequently. Conclusions. The frequency of gastric ulcer,
      duodenal ulcer and digestive bleeding was higher in patients who used NSAIDs.
      There was no connection found between endoscopic findings and dyspeptic symptoms.

PMID- 24941262
TI  - Cool temperatures reduce antifungal activity of symbiotic bacteria of threatened
      amphibians--implications for disease management and patterns of decline.
AB  - Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is a
      widespread disease of amphibians responsible for population declines and
      extinctions. Some bacteria from amphibians' skins produce antimicrobial
      substances active against Bd. Supplementing populations of these cutaneous
      antifungal bacteria might help manage chytridiomycosis in wild amphibians.
      However, the activity of protective bacteria may depend upon environmental
      conditions. Biocontrol of Bd in nature thus requires knowledge of how
      environmental conditions affect their anti-Bd activity. For example, Bd-driven
      amphibian declines have often occurred at temperatures below Bd's optimum range.
      It is possible these declines occurred due to reduced anti-Bd activity of
      bacterial symbionts at cool temperatures. Better understanding of the effects of
      temperature on chytridiomycosis development could also improve risk evaluation
      for amphibian populations yet to encounter Bd. We characterized, at a range of
      temperatures approximating natural seasonal variation, the anti-Bd activity of
      bacterial symbionts from the skins of three species of rainforest tree frogs
      (Litoria nannotis, Litoria rheocola, and Litoria serrata). All three species
      declined during chytridiomycosis outbreaks in the late 1980s and early 1990s and
      have subsequently recovered to differing extents. We collected anti-Bd bacterial
      symbionts from frogs and cultured the bacteria at constant temperatures from 8 
      degrees C to 33  degrees C. Using a spectrophotometric assay, we monitored Bd
      growth in cell-free supernatants (CFSs) from each temperature treatment. CFSs
      from 11 of 24 bacteria showed reduced anti-Bd activity in vitro when they were
      produced at cool temperatures similar to those encountered by the host species
      during population declines. Reduced anti-Bd activity of metabolites produced at
      low temperatures may, therefore, partially explain the association between Bd
      driven declines and cool temperatures. We show that to avoid inconsistent
      antifungal activity, bacteria evaluated for use in chytridiomycosis biocontrol
      should be tested over a range of environmental temperatures spanning those likely
      to be encountered in the field.

PMID- 24941265
TI  - Perceived difficulty in use of everyday technology in persons with acquired brain
      injury of different severity: a comparison with controls.
AB  - OBJECTIVE: To compare the perceived difficulty in use of everyday technology in
      persons with acquired brain injury with different levels of severity of
      disability with that of controls. METHODS: This comparison study recruited 2
      samples of persons with acquired brain injury and controls, comprising a total of
      161 participants, age range 18-64 years. The long and short versions of the
      Everyday Technology Use Questionnaire and the Extended Glasgow Outcome Scale were
      used to evaluate participants. RESULTS: Persons with acquired brain injury
      demonstrated lower mean levels of perceived ability in use of everyday technology
      than controls (F = 21.84, degrees of freedom = 1, p < 0.001). Further analysis
      showed a statistically significant mean difference in perceived difficulty in use
      of everyday technology between persons with severe disability and good recovery,
      between persons with severe disability and controls, and between persons with
      moderate disability and controls. No significant mean difference was found
      between persons with severe disability and moderate disability, between persons
      with moderate disability and good recovery, and between persons with good
      recovery and controls. CONCLUSION: Perceived difficulty in using everyday
      technology is significantly increased among persons with acquired brain injury
      with severe to moderate disability compared with controls. Rehabilitation
      services should consider the use of everyday technology in order to increase
      participation in everyday activities after acquired brain injury.

PMID- 24941266
TI  - Lung nodule and functional changes in smokers after smoking cessation short-term
      treatment.
AB  - BACKGROUND: Tobacco smoke causes lung disfunction and inflammation. METHODS:
      Twenty-two consecutive smokers with undetermined lung nodules were included. All
      underwent a baseline imaging, exhaled carbon monoxide level evaluation and
      spirometry, repeated at three months from smoking cessation therapy. RESULTS: A
      significant reduction in size of the lung nodules was reported (p = .037) as a
      trend in number reduction (p = .11). A significant increase in blood arterial
      oxygen pressure (p < .0001), heart rate reduction (p < .01), and FEV1 increase (p
      < .0001) was recorded. CONCLUSIONS: Smoking cessation reduces number and size of
      lung nodules and improves in lung functionality.

PMID- 24941268
TI  - Editorial.

PMID- 24941267
TI  - Simultaneous imaging of amyloid-beta and lipids in brain tissue using antibody
      coupled liposomes and time-of-flight secondary ion mass spectrometry.
AB  - The spatial localization of amyloid-beta peptide deposits, the major component of
      senile plaques in Alzheimer's disease (AD), was mapped in transgenic AD mouse
      brains using time-of-flight secondary ion mass spectrometry (ToF-SIMS),
      simultaneously with several endogenous molecules that cannot be mapped using
      conventional immunohistochemistry imaging, including phospholipids, cholesterol
      and sulfatides. Whereas the endogenous lipids were detected directly, the amyloid
      beta deposits, which cannot be detected as intact entities with ToF-SIMS because
      of extensive ion-induced fragmentation, were identified by specific binding of
      deuterated liposomes to antibodies directed against amyloid-beta. Comparative
      investigation of the amyloid-beta deposits using conventional
      immunohistochemistry and fluorescence microscopy suggests similar sensitivity but
      a more surface-confined identification due to the shallow penetration depth of
      the ToF-SIMS signal. The recorded ToF-SIMS images thus display the localization
      of lipids and amyloid-beta in a narrow (~10 nm) two-dimensional plane at the
      tissue surface. As compared to a frozen nontreated tissue sample, the liposome
      preparation protocol generally increased the signal intensity of endogenous
      lipids, likely caused by matrix effects associated with the removal of salts, but
      no severe effects on the tissue integrity and the spatial distribution of lipids
      were observed with ToF-SIMS or scanning electron microscopy (SEM). This method
      may provide an important extension to conventional tissue imaging techniques to
      investigate the complex interplay of different kinds of molecules in
      neurodegenerative diseases, in the same specimen. However, limitations in target
      accessibility of the liposomes as well as unspecific binding need further
      consideration.

PMID- 24941269
TI  - Does long-term medication with lithium, clozapine or antidepressants prevent or
      attenuate dementia in bipolar and depressed patients?
AB  - Background. Recent preclinical research suggests that lithium, clozapine, and
      possibly even antidepressants, have neurotrophic and neuroprotective properties.
      However, it remains unclear whether their long-term use can prevent the
      development of dementia or attenuate its severity in patients with major mood
      disorders. Method. Subjects included patients with bipolar disorder (N=220) and
      major depressive disorder (N=186) admitted between 1959 and 1963 and followed
      from 1965 to 1985. The presence of dementia was assessed clinically using ICD-9
      criteria, and functioning was determined with the Global Assessment Schedule
      (GAS). Long-term medication with lithium, clozapine and antidepressants was
      documented. Results. In the total sample, the occurrence of dementia correlated
      only with age. In a restricted analysis of the 88 patients with dementia, age
      became non-significant and lithium showed a trend to an inverse correlation with
      the severity of dementia. In the subgroup of bipolar demented patients, both
      lithium and clozapine medication were inversely related to the severity of
      dementia. Conclusions. The results are consistent with an attenuating effect of
      lithium and possibly clozapine on the development of severe dementia.
      Limitations. The sample of patients with dementia was small and the results are
      based on a naturalistic study. Dementia was only assessed once, without the use
      of cognitive measures. 

PMID- 24941270
TI  - A program for parents of teens with anorexia nervosa and eating disorder not
      otherwise specified.
AB  - Objective. This study investigates the effects of a multidisciplinary education
      and support program for parents of adolescents with anorexia nervosa. Methods.
      This was a case-control study with 29 prospective cases and 53 retrospective
      controls. Parents of 10-17-year-old patients hospitalized due to medical
      complications of their eating disorders were invited to participate. These
      parents were offered a multidisciplinary education and support program. At the
      termination of the hospitalization, parents completed a survey examining their:
      knowledge about the treatment course of eating disorders, inclusion in their
      child's care and preparedness to care for their child at home. Results. Using two
      tailed t-tests, results indicate that study parents felt: more knowledgeable
      about the treatment course for eating disorders (p<0.001), less excluded from
      their child's care (p=0.001), more prepared to take their child home (p<0.001),
      and that they had a better idea of what to feed their child at home (p<0.001).
      Conclusion. These results suggest that providing multidisciplinary education and
      support to parents of hospitalized adolescents with eating disorders helps to
      improve their feelings of inclusion in and knowledge about the treatment course,
      and increases their perceived ability to care for and re-nourish their child upon
      discharge. 

PMID- 24941271
TI  - Psychiatric disorders in patients with Behcet's disease.
AB  - Objective. In this study, we aimed to investigate current prevalence and related
      clinical factors of psychiatric disorders in Behcet patients. Methods. Seventy
      three outpatients who applied to a Behcet clinic and whose diagnosis was Behcet's
      disease according to criteria of the International Study Group for Behcet's
      disease were recruited in this study. Psychiatric diagnoses were assessed with
      The Structured Clinical Interview for DSM-IV/Clinical Version (SCID-I/CV).
      Results. Thirty patients (41.1%) reported at least one current psychiatric
      disorder. Major depression (17.8%) was the most frequent psychiatric disorder.
      Specific phobia (16.4%), generalized anxiety disorder (15.1%) and social phobia
      (9.6%) were other frequent disorders. Prevalence rates of any psychiatric and
      anxiety disorder were significantly higher in females than males. There was no
      significant relationship between psychiatric morbidity and clinical
      characteristics of Behcet's disease. Conclusion. Our study suggests that Behcet
      patients have high prevalence of psychiatric disorders. Therefore, psychiatric
      evaluation should be performed in all patients with Behcet's disease. 

PMID- 24941272
TI  - A gender-oriented comparison between the mental health profiles of Bulgarian
      immigrants forcibly migrated to Turkey and the native population 15 years after
      migration.
AB  - Background. The considerable problem of the migration of people, mainly from
      developing or undeveloped countries to developed countries, is a worldwide issue.
      The aims of this study were to compare, according to gender, scores obtained
      pertaining to mental symptom distributions of Bulgarian immigrants arriving in
      one city of west Turkey in 1989 with those of native-born citizens, as well as to
      the scores obtained from the scales of anxiety, hopelessness, job and life
      satisfaction. Methods. During the period of study between 1 February and 31 April
      2003, short symptom inventory, state and trait anxiety scales, and hopelessness,
      job, and life satisfaction scales were collected from 85 immigrants living in a
      district where immigrants are prevalent. The results of 98 of the native
      population living in the same district were also collected during the same
      period. Data were analyzed using chi-square, t, Mann-Whitney U-tests, and percent
      ratios. RESULTS: Upon comparison of the scores of both immigrant women and native
      women, and immigrant men and native men, no differences were found between scores
      obtained from the subscales of short symptom inventory, state and trait anxiety
      scales, and hopelessness and job satisfaction scales (p>0.05). The only
      observable difference was between scores obtained from the life satisfaction
      scale (p<0.01 and p<0.05, respectively). The depression subscale of the short
      symptom inventory revealed a difference in the scores of immigrant women compared
      to immigrant men, as did the somatization subscale for native-born women when
      compared to native men (p<0.05 and p<0.05, respectively). CONCLUSIONS: That both
      male and female immigrants had low scores for life satisfaction forces us to draw
      the conclusion that their expectations, necessities, desires and wishes were not
      entirely fulfilled. The reason for their being no observable differences between
      the other scale scores may be attributed to the fact that the immigrant women and
      men share not only the same ethnic origin, but also historical and cultural ties
      with those in Turkey. An alternative view could be that those entering the
      country may have adapted to the environment after the passage of 15 years.
      Furthermore, the significant difference seen between immigrant women and men, and
      native women and men in terms of symptoms of depression and somatization,
      respectively, may be explained through the notion that women perceived migration
      to be more different, and that native women more readily accepted the thought of
      physical illness according to mental disorders. Further studies are needed to
      better explain some of these results.

PMID- 24941273
TI  - Antipsychotic drug use in 503 Chinese inpatients with schizophrenia.
AB  - Objective. To determine current patterns of antipsychotic medication use and
      metabolic complications among hospitalized Chinese patients with schizophrenia.
      Method. A total of 503 inpatients who met ICD-10 diagnostic criteria for
      schizophrenia were enrolled. Demographic features and records of current
      treatment (medication, dose, duration of treatment) were collected through cross
      sectional chart review along with biophysical parameters (body mass index and
      laboratory findings). Results. (1) Most patients (457/503, 90.9%) were found to
      receive antipsychotic monotherapy; (2) clozapine was the most common medication
      used (152/507, 30.2%); (3) the subset of patients treated within the course of a
      first episode psychosis, or with less than 5 years of illness, were more likely
      to be treated with second-generation antipsychotics (SGAs) than with conventional
      antipsychotic medications or clozapine; (4) patients treated with clozapine or
      conventional antipsychotics were more likely to manifest metabolism-related
      physical conditions than those receiving SGAs. Conclusion. Conventional
      antipsychotics and clozapine constitute the current mainstream of schizophrenia
      treatment in China where a lower percentage of patients receive SGAs other than
      clozapine than in developed countries. The high incidence of treatment-related
      metabolic complications in this population suggests that these issues are under
      appreciated based on current patterns of medication use. 

PMID- 24941275
TI  - Escitalopram in major depressive disorder: clinical benefits and cost
      effectiveness versus citalopram.
AB  - Objective. Escitalopram is the most selective of the serotonin reuptake
      inhibitors. Methods. We review all the clinical trials (three pivotal placebo
      controlled trials with citalopram as an active reference, one long-term non
      inferiority study and one head-to-head superiority study) that include citalopram
      as an active reference in major depressive disorder (MDD), and studies that
      evaluate the cost-effectiveness of the two drugs. Results. In two of the pivotal
      studies and in the long-term study, escitalopram was numerically better than
      citalopram in reducing Montgomery-Asberg Depression Rating Scale (MADRS) scores
      from baseline, with comparative tolerability. Meta-analyses of these studies
      showed statistically significant differences in favour of escitalopram in terms
      of reducing MADRS and increasing response. This effect was particularly apparent
      in patients with higher baseline MADRS scores. These trends were confirmed in a
      head-to-head study, which clearly demonstrated the superiority of escitalopram
      compared with citalopram on primary and secondary endpoints. The difference
      between treatments was clinically relevant. Cost-effectiveness analyses
      demonstrated that although escitalopram has a slightly higher unit cost than
      generic citalopram, expected direct medical and productivity- related costs were
      lower with escitalopram than citalopram. Conclusion. On the basis of these
      results, escitalopram was concluded to be more clinically effective and more cost
      effective than citalopram for the treatment of MDD, with a similar tolerability
      profile. 

PMID- 24941274
TI  - Psychometric properties of the BASIS-24(c) (Behaviour and Symptom Identification
      Scale-Revised) Mental Health Outcome Measure.
AB  - Objective. Outcome measurement in mental health services is an area of
      considerable clinical interest and policy priority. This study sought to assess
      the Behaviour and Symptom Identification Scale-24 (BASIS-24(c)), a brief, patient
      self-reported measure of psychopathology and functioning, in a UK sample,
      including establishing population norms for comparative purposes. Methods.
      Participants were 588 adults recruited from psychiatric inpatient, outpatient and
      primary care settings; and 630 adults randomly sampled from primary care lists
      who completed the BASIS-24(c), and the Brief Symptom Inventory (BSI) at two time
      points. Results. BASIS-24(c) demonstrated adequate reliability (coefficient alpha
      values for combined clinical sample across subscales ranged from 0.75 to 0.91),
      validity and responsiveness to change (effect size for change of the BASIS-24(c)
      was 0.56 compared with 0.48 for BSI Global Severity Index). Population norms were
      established for the general population and adult in-patients (at in-take). The
      scale proved straightforward to complete across clinical settings. Variable rates
      of questionnaire distribution across clinical settings highlighted the ongoing
      challenge of incorporating outcome measures in clinical settings. Conclusion.
      BASIS-24(c) is a brief, easily administered, self-complete measure of mental well
      being and functioning that adequately meets the requirements of reliability,
      validity and responsiveness to change required of an outcome measure. 

PMID- 24941276
TI  - Validation of the factorial structure of the Positive and Negative Syndrome Scale
      in use by untrained psychiatrists in routine care.
AB  - Background. The Positive and Negative Syndrome Scale (PANSS) can be called the
      standard for the assessment of schizophrenic disorders. It is well-known and
      routinely used. In scientific studies and clinical practice extensive training of
      raters in the use of the scale can often not be provided. The question is whether
      under such conditions psychometric properties of the scale can be guaranteed.
      Method. In a 2-year drug utilization study on risperidone, 1895 schizophrenic
      outpatients were assessed by their treating psychiatrists, who were working under
      conditions of routine care, using a modified version of the Positive and Negative
      Symptom Scale (PANSS/m). Physicians could not be trained in the use of the scale.
      The results of these ratings were analysed, comparing means and internal
      consistency with the original Kay et al. results (Kay et al. The positive and
      negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261),
      and by factor analysis for the total sample and split halves. Results. Means for
      the positive subscale were similar (6.5 and 6.4, respectively) and means for the
      negative subscale (11.9 and 8.0, respectively) slightly higher than the original
      Kay et al. results. Internal consistency of the positive and negative subscales
      (0.80 and 0.87, and 0.73 and 0.83, respectively) were similar to Kay et al. The
      same clear factorial solution was found for the total sample and the subsamples.
      Discussion. Scores for the subscales reflect the predominance of negative
      symptoms in schizophrenic outpatients. The factorial solution supports the
      positive and negative subscales of the PANSS. The PANSS/m was easy to use under
      conditions of routine treatment and is a good and robust scale. 

PMID- 24941277
TI  - Management of acutely ill patients in the hospital setting: focus on quetiapine.
AB  - We have considered published work and clinical experience focusing on the
      atypical antipsychotic quetiapine in order to form a consensus on the most
      appropriate treatment strategies for hospitalised patients with acute
      schizophrenia or bipolar disorder. It is important to consider the specific
      treatment needs of these patients and these are discussed in the context of
      current treatment guidelines. We will review the efficacy and tolerability of
      atypical antipsychotics versus conventional antipsychotics and/or benzodiazepines
      as a first-line treatment, and examine the suitability of oral versus
      intramuscular formulations in the acute setting. The potentially beneficial
      properties of specific atypical agents are also considered. Appropriate dosing is
      particularly important in acutely ill patients as it can help achieve rapid
      improvement. We will discuss emerging data which show that rapid initiation of
      quetiapine in patients with acute psychosis or mania is not only as effective as
      standard initiation, but is also well tolerated. This may be important for
      treatment in the long term as a positive initial treatment experience can
      determine patient compliance and treatment adherence. In conclusion, this review
      recommends that oral atypical antipsychotics should be a first-choice medication
      for acutely ill cooperative patients in the hospital setting. 

PMID- 24941278
TI  - A naturalistic study of the relationship between self-harm behaviors and Axis I
      diagnostic groupings among inpatients.
AB  - Self-harm behavior is relatively common among psychiatric patients, but few
      studies have examined such behavior in the context of Axis I diagnoses. In this
      study among 110 psychiatric inpatients, we examined clinical psychiatric
      diagnoses and surveyed participants for self-harm behaviors. Surprisingly, using
      five diagnostic groupings, there were no between-group differences in the
      endorsement of individual, total number of, or high-lethal self-harm behaviors.
      Our results suggest that the number and character of self-harm behaviors does not
      relate to psychiatric diagnosis among psychiatric inpatients. 

PMID- 24941279
TI  - Panic attacks after treatment with zuclopenthixol decanoate.
AB  - The association between neuroleptics and anxiety is unclear: neuroleptics have
      been used to treat anxiety though may also themselves be anxiogenic. We present
      the case of a man who developed new onset panic attacks after treatment with
      zuclopenthixol decanoate, a commonly administered depot antipsychotic. We review
      the literature on the association between antipsychotics and anxiety and present
      possible pathophysiological mechanisms. 

PMID- 24941282
TI  - Letter to the editors.

PMID- 24941283
TI  - 2006 peer review panel.

PMID- 24941285
TI  - Effect of Dunaliella tertiolecta organic exudates on the Fe(II) oxidation
      kinetics in seawater.
AB  - The role played by the natural organic ligands excreted by the green algae
      Dunaliella tertiolecta on the Fe(II) oxidation rate constants was studied at
      different stages of growth. The concentration of dissolved organic carbon
      increased from 2.1 to 7.1 mg L(-1) over time of culture. The oxidation kinetics
      of Fe(II) was studied at nanomolar levels and under different physicochemical
      conditions of pH (7.2-8.2), temperature (5-35  degrees C), salinity (10-37), and
      dissolved organic carbon produced by cells (2.1-7.1 mg L(-1)). The experimental
      rate always decreased in the presence of organic exudates with respect to that in
      the control seawater. The Fe(II) oxidation rate constant was also studied in the
      context of Marcus theory, where DeltaG degrees  was 39.31-51.48 kJ mol(-1). A
      kinetic modeling approach was applied for computing the equilibrium and rate
      constants for Fe(II) and exudates present in solution, the Fe(II) speciation, and
      the contribution of each Fe(II) species to the overall oxidation rate constant.
      The best fit model took into account two acidity equilibrium constants for the
      Fe(II) complexing ligands with pKa,1=9.45 and pKa,2=4.9. The Fe(II) complexing
      constants were KFe(II)-LH=3*10(10) and KFe(II)-L=10(7), and the corresponding
      computed oxidation rates were 68+/-2 and 36+/-8 M(-1) min(-1), respectively.

PMID- 24941287
TI  - Quantum dot-sensitized hierarchical micro/nanowire architecture for
      photoelectrochemical water splitting.
AB  - We report the fabrication of quantum dot-sensitized hierarchical structure and
      the application of the structure as a photoanode for photoelectrochemical water
      splitting. The structure is synthesized by hydrothermally growing ZnO nanowires
      on silicon microwires grown with the vapor-liquid-solid method. Then the
      hierarchical structure is further sensitized with CdS and CdSe quantum dots and
      modified with IrOx quantum dots. As a result, the silicon microwires, ZnO
      nanowires, and the quantum dot/ZnO core/shell structure form a multiple-level
      hierarchical heterostructure, which is remarkably beneficial for light absorption
      and charge carrier separation. Our experimental results reveal that the
      photocurrent density of our multiple-level hierarchical structure achieves a
      surprising 171 times enhancement compared to that from simple ZnO nanowires on a
      planar substrate. In addition, the photoanode shows high stability during the
      water-splitting experiment. These results prove that the quantum dot-sensitized
      hierarchical structure is an ideal candidate for a photoanode in solar water
      splitting applications. Importantly, the modular design approach we take to
      produce the photoanode allows for the integration of future discoveries for
      further improvement of its performance. 

PMID- 24941286
TI  - Improving nutrition and physical activity policies in afterschool programs:
      results from a group-randomized controlled trial.
AB  - OBJECTIVE: Afterschool programs can be health-promoting environments for
      children. Written policies positively influence nutrition and physical activity
      (PA) environments, but effective strategies for building staff capacity to write
      such policies have not been evaluated. This study measures the comprehensiveness
      of written nutrition, PA, and screen time policies in afterschool programs and
      assesses impact of the Out of School Nutrition and Physical Activity (OSNAP)
      intervention on key policies. METHODS: Twenty afterschool programs in Boston, MA
      participated in a group-randomized, controlled trial from September 2010 to June
      2011. Intervention program staff attended learning collaboratives focused on
      practice and policy change. The Out-of-School Time (OST) Policy Assessment Index
      evaluated written policies. Inter-rater reliability and construct validity of the
      measure and impact of the intervention on written policies were assessed.
      RESULTS: The measure demonstrated moderate to excellent inter-rater reliability
      (Spearman's r=0.53 to 0.97) and construct validity. OSNAP was associated with
      significant increases in standards-based policy statements surrounding snacks
      (+2.6, p=0.003), beverages (+2.3, p=0.008), screen time (+0.8, p=0.046), family
      communication (+2.2, p=0.002), and a summary index of OSNAP goals (+3.3, p=0.02).
      CONCLUSIONS: OSNAP demonstrated success in building staff capacity to write
      health-promoting policy statements. Future research should focus on determining
      policy change impact on practices.

PMID- 24941289
TI  - Regulation of myelopoiesis by CD137L signaling.
AB  - CD137 ligand (CD137L) has emerged as a powerful regulator of myelopoiesis that
      links emergency situations, such as infections, to the generation of additional
      myeloid cells, and to their activation and maturation. CD137L is expressed on the
      cell surface of hematopoietic stem and progenitor cells (HSPC) and antigen
      presenting cells (APC) as a transmembrane protein. The signaling of CD137L into
      HSPC induces their proliferation and differentiation to monocytes and
      macrophages, and in monocytes CD137L signaling induces differentiation to potent
      dendritic cells (DC). CD137L signaling is initiated by CD137 which is expressed
      by T cells, once they become activated. Some of these activated, CD137-expressing
      T cells migrate from the site of infection to the bone marrow where they interact
      with HSPC to induce myelopoiesis, or they induce monocyte to DC differentiation
      locally at the site of infection. Therapeutically, induction of CD137L signaling
      can be utilized to reinitiate myeloid differentiation in acute myeloid leukemia
      cells, and to generate potent DC for immunotherapy. 

PMID- 24941290
TI  - Fire activity and severity in the western US vary along proxy gradients
      representing fuel amount and fuel moisture.
AB  - Numerous theoretical and empirical studies have shown that wildfire activity
      (e.g., area burned) at regional to global scales may be limited at the extremes
      of environmental gradients such as productivity or moisture. Fire activity,
      however, represents only one component of the fire regime, and no studies to date
      have characterized fire severity along such gradients. Given the importance of
      fire severity in dictating ecological response to fire, this is a considerable
      knowledge gap. For the western US, we quantify relationships between climate and
      the fire regime by empirically describing both fire activity and severity along
      two climatic water balance gradients, actual evapotranspiration (AET) and water
      deficit (WD), that can be considered proxies for fuel amount and fuel moisture,
      respectively. We also concurrently summarize fire activity and severity among
      ecoregions, providing an empirically based description of the geographic
      distribution of fire regimes. Our results show that fire activity in the western
      US increases with fuel amount (represented by AET) but has a unimodal (i.e.,
      humped) relationship with fuel moisture (represented by WD); fire severity
      increases with fuel amount and fuel moisture. The explicit links between fire
      regime components and physical environmental gradients suggest that multivariable
      statistical models can be generated to produce an empirically based fire regime
      map for the western US. Such models will potentially enable researchers to
      anticipate climate-mediated changes in fire recurrence and its impacts based on
      gridded spatial data representing future climate scenarios. 

PMID- 24941291
TI  - Evaluating a sodium dispersion reagent for the Bouveault-Blanc reduction of
      esters.
AB  - A new sodium dispersion reagent has been evaluated for the reduction of esters.
      Na-D15, a sodium dispersion with sodium particle size of 5-15 MUm, is a
      nonpyrophoric reagent that can be handled in air. In this study, a broad range of
      aliphatic ester substrates were reduced to primary alcohols by Na-D15/i-PrOH with
      good yields. The method compares favorably with modern metal hydride reductions
      and is much safer and efficient than the traditional Bouveault-Blanc reduction. 

PMID- 24941292
TI  - Protective effect of Acacia ferruginea against ulcerative colitis via modulating
      inflammatory mediators, cytokine profile and NF-kappaB signal transduction
      pathways.
AB  - In the present study, we evaluated the protective effect of A. ferruginea extract
      against ulcerative colitis (UC). Male Wistar rats received A. ferruginea extract
      (10 mg/kg body weight) or sulfasalazine (100 mg/kg body weight) for 5 consecutive
      days before inducing UC via intrarectal acetic acid (3%) administration. Colonic
      mucosal injury was assessed by macroscopic scoring, vascular permeability
      testing, and histopathological examination. The mucosal contents of glutathione,
      lipid peroxidation, superoxide dismutase, and nitric oxide were evaluated as
      parameters for the redox state. Inflammatory response was determined by measuring
      inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) expression.
      Myeloperoxidase (MPO), lactate dehydrogenase assay (LDH), tumor necrosis factor
      (TNF-alpha), and interleukins (IL-1beta and IL-6) were measured using ELISA.
      Transcription factor profiling of nuclear factor (NF)-kappaB subunits (p65/p50)
      was also conducted using ELISA. All of the relevant parameters were altered in
      rats with UC, and these parameters improved in animals that received A.
      ferruginea extract. Colonic mucosal injury parallels antioxidant and anti
      inflammatory evaluations, and A. ferruginea extract was considered comparable to
      the standard treatment drug sulfasalazine. Histopathological studies confirmed
      these findings. A. ferruginea extract inhibited the activation and translocation
      of transcription factors, that is, NF-kappaB subunits (p65/p50). The results of
      our investigation clearly indicate that treatment with A. ferruginea extract
      exerted a marked protective effect against experimental UC via modulation of
      oxidant/anti-oxidant balance and inhibition of inflammatory mediators. 

PMID- 24941293
TI  - In vivo toxicity of the culturable marine cyanobacterium Geitlerinema
      pseudacutissimum CNP 1019 extract on male Swiss albino mice (Mus musculus).
AB  - In this study, we investigated the in vivo toxicity of Geitlerinema
      pseudacutissimum CNP 1019 organic extract in a murine host. A single
      intraperitoneal injection of 1 g extract kg-1 body weight (BW) did not exhibit
      mortality, whereas 3 g extract kg-1 BW (approximate lethal dose) resulted in
      mortality within 5 days. To perform subchronic exposure toxicity analyses (i.e.,
      daily exposure for a total of 14 days), a maximum concentration of <=1 g extract
      kg-1 BW was used. Subchronic toxicity studies in the treated mice, showed
      fluctuations of feed intake, loss of body weight, increase in specific activity
      of serum lactate dehydrogenase, alanine aminotransferase and decrease in whole
      serum protein concentration. LDH isoenzyme expression was found, and levels of
      the various isoforms were decreased as a result of the treatment. Histopathology
      studies in liver, kidney, and spleen isolated from the treated mice showed the
      presence of necrotic debris, hemorrhage, and micronuclei revealing the toxicity
      of the extract. The dose-dependent alterations in biochemical parameters in
      conjunction with the histological lesions noted in the animals treated with the
      prepared extract illustrate the likely potential toxicity to mammals from any
      encounters with the studied cyanobacterium.

PMID- 24941294
TI  - Relationship between genotoxic effects of breast cancer treatments and patient
      basal DNA integrity.
AB  - Radiotherapy and chemotherapy cause genotoxic side effects that are highly
      variable among patients. In this study, we evaluated DNA integrity using the
      comet assay in peripheral blood lymphocytes from breast cancer patients before
      ("pre-treatment patients"; n=47) and after ("post-treatment patients"; n=24)
      radiotherapy and/or chemotherapy treatment and from healthy donors (n=15). Comet
      evaluation was made by visual (types 0-4) and digital (percentage of DNA
      remaining in the comet head=% head DNA) analysis. The association between the
      level of DNA damage and cancer prognostic factors was assessed. The treatments
      caused a significant increase in DNA damage registered by both visual (p<0.001)
      and digital (p<0.001) analyses. No significant associations between the level of
      DNA damage in pre-treatment patients and cancer prognostic factors were found. A
      significant correlation between the comet results from each patient before and
      after treatment (r=0.64, p=0.001) was observed. The % head DNA in post-treatment
      samples from patients with a high level of DNA damage before treatment (30.3+/
      3.1%, p<0.01) was lower than in post-treatment samples from patients with a low
      to-medium level of DNA damage before therapy (49.2+/-4.4%). These results support
      the usefulness of the comet assay as a sensitive technique to evaluate basal DNA
      status and DNA damage caused by cancer treatments. The comet assay could
      contribute to treatment decisions, especially by taking into account the
      patient's basal DNA damage before therapy.

PMID- 24941295
TI  - Effects of maternally exposed food coloring additives on laryngeal histology in
      rats.
AB  - Experimental reports showed carcinogenic effects of artificial food colors and
      additives (AFCAs) on many organs, including the head and neck region. We aimed to
      investigate the effect of AFCAs on laryngeal histomorphology and
      immunohistochemical expression in maternally exposed rats. "No observable adverse
      effect levels" of commonly used AFCAs as a mixture were given to female rats
      before and during gestation. Histopathological and immunohistochemical findings
      were evaluated in their offspring. Significant decreasing in goblet cell count
      and cilia loss were observed with AFCAs in maternally exposed rats (p<0.05).
      Immunohistochemically, the Ki67 index was significantly increased and villin
      expression was significantly reduced in laryngeal epithelium in the study group
      (p<0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and
      epidermal growth factor receptors did not differ between the groups. This study
      demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense
      system and possibly in carcinogenesis.

PMID- 24941296
TI  - Antioxidant and hepatoprotective effects of Crataegus songarica methanol extract.
AB  - The protective activity of the methanolic extract of the Crataegus songarica
      leaves was investigated against CCl4- and paracetamol-induced liver damage. On
      folklore levels, this plant is popularly used to treat various toxicological
      diseases. We evaluated both in vitro and ex vivo antioxidant activity of C.
      songarica. At higher concentration of plant extract (700 ug/ml), 88.106%
      inhibition on DPPH radical scavenging activity was observed and reducing power of
      extract was increased in a concentration-dependent manner. We also observed its
      inhibition on Fe2+/ascorbic acid-induced lipid peroxidation on rat liver
      microsomes in vitro. In addition, C. songarica extract exhibited antioxidant
      effects on calf thymus DNA damage induced by Fenton reaction. Hepatotoxicity was
      induced by challenging the animals with CCl4 (1 ml/kg body weight, i.p.) and
      paracetamol (500 mg/kg body weight) and the extract was administered at three
      concentrations (100, 200, and 300 mg/kg body weight). Hepatoprotection was
      evaluated by determining the activities of liver function marker enzymes and
      antioxidant status of liver. Administration of CCl4 elevated the levels of liver
      function enzymes, SGOT, SGPT, and LDH. We also observed a dramatic increase in
      ALT, AST, bilirubin, and alkaline phosphatase levels in rats administered 500
      mg/kg body weight of paracetamol. Decreased antioxidant defense system as
      glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), glutathione
      reductase (GR), glutathione-S-transferase (GST), and superoxide dismutase (SOD)
      were observed in rats treated with CCl4 and paracetamol. Pretreatment with the
      extract decreased the elevated serum GOT, GPT, LDH, bilirubin, and alkaline
      phosphatase activities and increased the antioxidant enzymes in a dose-dependent
      manner. Therefore, C. songarica methanol extract may be an effective hepatic
      protective agent and viable candidate for treating hepatic disorders and other
      oxidative stress-related diseases. 

PMID- 24941297
TI  - Antitumor and wound healing properties of Rubus niveus Thunb. root.
AB  - The main objective of this study is to highlight the importance of Rubus niveus
      in the pharmaceutical industry for the development of cost-effective drugs. The
      study was undertaken to explore the HPLC profile, wound healing, antitumor, and
      free radical scavenging properties of R. niveus. The root of R. niveus was
      extracted using organic solvents and subjected to in vitro antioxidant assays.
      Acetone extract, which showed better in vitro antioxidant properties, was
      evaluated for in vivo antioxidant, wound healing, and antitumor properties. The
      polyphenolic acetone extract showed significant in vivo antioxidant, wound
      healing, and antitumor properties. In the wound healing study, complete
      epithelialization was noticed during the 13th to 17th days for treated groups.
      The 250 mg/kg group was found to prolong the life span of mice with Ehrlich
      ascites carcinoma (70.04%) and reduced the volume of Daltons lymphoma ascites
      solid tumors (2.07 cm3). The HPLC analysis of acetone extract revealed the
      presence of Quercetin, a natural flavonoid with the retention time of 20.89 min.
      The results of the current study suggest the use of R. niveus as a valuable
      natural antioxidant that has an immense scope as an effective source to cure skin
      diseases, wounds, and tumors. 

PMID- 24941298
TI  - Epigenetic targets of polyphenols in cancer.
AB  - Interest in dietary polyphenols has recently increased greatly owing to their
      antioxidant capacity and their possible beneficial implications in various
      pathological states, including cancer. Polyphenols are a group of chemicals found
      in many fruits, vegetables, and plants and have the ability to remove free
      radicals from the body. In the last 2 decades, the numbers of reports on the
      potential health benefits of polyphenols have increased. This review provides the
      available scientific data that justify importance of polyphenols in correlation
      with epigenetics to fight against carcinogenesis. Epigenetics involves genetic
      control by mechanisms other than DNA sequence. These epigenetic mechanisms have
      ability to switch on or off various important genes influencing the process of
      cancer. Furthermore, due to the reversible nature of these epigenetic mechanisms,
      they are influenced by a variety of dietary polyphenols. This review focuses on
      the dietary polyphenols that significantly affect these epigenetic mechanisms to
      mitigate carcinogenesis. 

PMID- 24941299
TI  - Reversal of methylmercury-induced oxidative stress, lipid peroxidation, and DNA
      damage by the treatment of N-acetyl cysteine: a protective approach.
AB  - This study was designed to evaluate the protective effect of N-acetyl cysteine in
      reducing methylmercury (MeHg)-induced oxidative stress, lipid peroxidation, DNA
      damage in liver, kidney, and brain, and their ability to restore altered hepatic,
      renal, and other biochemical variables. Male Sprague-Dawley rats (150+/-10 g)
      were randomly divided into three groups. Group 1 served as the control. Groups 2
      and 3 were administered methylmercury (1 mg kg-1 orally, 5 days/week) for 12
      weeks, and group 2 served as the experimental control. Group 3 received N-acetyl
      cysteine (0.6 mg kg-1 intraperitoneally, two days/week) for 12 weeks after
      methylmercury exposure. Methylmercury exposure caused a significant rise in
      bilirubin, gamma-glutamyl transpeptidase, protein, triglycerides, cholesterol,
      urea, creatinine, uric acid, and blood urea nitrogen, with a concomitant decrease
      in albumin content, reduced glutathione level and acetyl cholinesterase activity,
      antioxidant enzymes such as glutathione reductase, glutathione peroxidase,
      glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. However, lipid
      peroxidation level, metallothionein expression, and DNA damage with increment of
      tail length were observed after methylmercury intoxication. N-acetyl cysteine, a
      widely available, nontoxic amino acid derivative, is a promising antioxidant with
      a wide spectrum of biological functions. The ability of N-acetyl cysteine to
      enhance mercury excretion and its wide availability in clinical use indicate that
      it may be an ideal therapeutic agent against methylmercury poisoning.

PMID- 24941300
TI  - The influence of contrast media on kidney function in patients with stable
      coronary artery disease.
AB  - AIMS: To investigate the incidence of contrast media-induced nephropathy (CIN) in
      patients with stable coronary artery disease (CAD) referred for elective coronary
      intervention following hydration routines. The reversibility of CIN was followed
      in a 6 month-period. METHODS AND RESULTS: A total of 447 patients referred for
      elective coronary intervention due to suspected CAD were included. Blood samples
      were collected before and 24 h after intervention and medical records were
      obtained. Patients had no drinking fluid restrictions and were routinely treated
      with a 1000 ml saline infusion. All patients were invited to a 6-month
      examination and collection of blood samples. RESULTS: A total of 19 patients
      (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated
      glomerular filtration rate (eGRF), lower level of kidney failure and lower
      creatinine level than non-CIN patients. Kidney function was not normalized in CIN
      patients 6 months after the intervention. Two patients still met the definition
      of CIN. CONCLUSION: With no restriction in fluid intake and supplementary
      infusion of saline, only a few patients with stable CAD developed early
      indications of CIN during elective coronary interventions. Kidney function and
      the amount of contrast media used was not a predictor of CIN development. The
      induced CIN was not completely normalized in a 6-month follow-up period.

PMID- 24941301
TI  - Zebrafish as a model system for environmental health studies in the grade 9-12
      classroom.
AB  - Developing zebrafish embryos were used as a model system for high school students
      to conduct scientific investigations that reveal features of normal development
      and to test how different environmental toxicants impact the developmental
      process. The primary goal of the module was to engage students from a wide range
      of socio-economic backgrounds, with particular focus on underserved inner-city
      high schools, in inquiry-based learning and hands-on experimentation. In
      addition, the module served as a platform for both teachers and students to
      design additional inquiry-based experiments. In this module, students spawned
      adult zebrafish to generate developing embryos, exposed the embryos to various
      toxicants, then gathered, and analyzed data obtained from control and
      experimental embryos. The module provided a flexible, experimental framework for
      students to test the effects of numerous environmental toxicants, such as
      ethanol, caffeine, and nicotine, on the development of a model vertebrate
      organism. Students also observed the effects of dose on experimental outcomes.
      From observations of the effects of the chemical agents on vertebrate embryos,
      students drew conclusions on how these chemicals could impact human development
      and health. Results of pre-tests and post-tests completed by participating
      students indicate statistically significant changes in awareness of the impact of
      environmental agents on fish and human beings In addition, the program's
      evaluator concluded that participation in the module resulted in significant
      changes in the attitude of students and teachers toward science in general and
      environmental health in particular.

PMID- 24941302
TI  - Unusual location of chordoma metastasis.
AB  - BACKGROUND: Chordoma is a rare tumor originating from the remnants of the
      notochord. The tumor is known as locally aggressive with a strong tendency for
      recurrence rather than metastasis. CASE REPORT: We reported on a case of a 47
      year-old Caucasian male with a history of sacral chordoma with metastasis to the
      cicatrix. CONCLUSIONS: Skin involvement in chordoma is uncommon but, according to
      literature, possible. Nevertheless, to our knowledge, there were no reports on
      incisional chordoma.

PMID- 24941303
TI  - Paediatric trauma in the USA: patterns of emergency department visits and
      associated hospital resource use.
AB  - Trauma is the leading cause of mortality and morbidity among children in the USA.
      To examine the variation in the epidemiology and patterns of visits to emergency
      departments (EDs), and test the hypothesis that children evaluated at trauma
      centre EDs will have higher injury severity and a higher likelihood of
      hospitalisation versus those evaluated at non-trauma centre EDs, we analysed a
      national database of all injured children aged 0-20 years evaluated at US EDs in
      2009. Childhood injuries are a frequent cause of visits to US EDs, with a
      national point prevalence of 620 cases per 10,000 children aged 0-20 years.
      Epidemiology of childhood injuries in the USA is significant for male gender
      preponderance, significant seasonal and geographical variation, and
      disproportionately more frequent injury to the extremities than other sites of
      the body. National hospital resource use was significant, with greater burden
      borne by trauma centres which disproportionately provided care to the most
      severely injured children.

PMID- 24941304
TI  - A novel method for photolithographic polymer shadow masking: toward high
      resolution high-performance top-contact organic field effect transistors.
AB  - A novel and universal method, based on water-soluble poly(4-styrene sulfonate),
      was introduced into the preparation of a polymer mask. Using this mask, high
      resolution, high-performance, bottom-gate, top-contact OFETs can be achieved.
      There is no solvent intervention in the process of manufacturing these OFETs and
      the mask can be recycled. 

PMID- 24941305
TI  - Temperature- and pH-responsive micelles with collapsible poly(N
      isopropylacrylamide) headgroups.
AB  - We have studied the micelle formation and phase behavior of a series of
      temperature- and pH-responsive surfactants prepared by controlled radical (RAFT)
      polymerization. These C12NIPAMm surfactants consist of a dodecyl tail, a poly(N
      isopropylacrylamide) (polyNIPAM) headgroup with average degrees of polymerization
      of between 7 and 96, and an ionizable carboxylate group. In the un-ionized state,
      these surfactants phase separate on warming toward a lower critical solution
      temperature (LCST), which decreases as the length of the NIPAM group is
      decreased. This is in agreement with the behavior of conventional nonionic
      poly(ethylene oxide)-based surfactants but is very different from that of
      polyNIPAM oligomer solutions. Small angle neutron scattering (SANS) shows that
      these surfactants self-assemble into micelles consisting of a nearly spherical
      hydrophobic core surrounded by a "hairy" polyNIPAM shell far below their LCST.
      Upon warming, the micelles undergo a sphere-to-rod transition induced by the
      collapse of the polyNIPAM shell, causing a reduction in the headgroup area. In
      the un-ionized state the demixing follows at the LCST, but a single charge on the
      free polymer end completely suppresses phase separation, allowing micelles to
      undergo a shape change but remain dissolved. 

PMID- 24941306
TI  - Getting personal perspectives on individualized treatment duration in multidrug
      resistant and extensively drug-resistant tuberculosis.
AB  - Tuberculosis (TB) differs from most other bacterial infectious diseases by a very
      long duration of combination antibiotic therapy required to achieve relapse-free
      cure. Although the standard recommended "short-course" treatment length for TB is
      6 months, the World Health Organization recommends a duration of 20 months for
      the treatment of patients with multidrug-resistant and extensively drug-resistant
      TB (M/XDR-TB). Apart from the long duration of anti-TB therapy, treatment of
      M/XDR-TB is very expensive and often associated with adverse drug events. The
      optimal duration for treatment of TB likely differs between individuals and
      depends on a variety of variables, such as the extent of the disease, the immune
      status of the host, and the virulence and the drug resistance of the causative
      strain of Mycobacterium tuberculosis. Some patients with M/XDR-TB may have to be
      treated with currently available antituberculosis drug regimens for more than 20
      months, whereas much shorter treatment durations may be possible to achieve cure
      for the majority of patients with M/XDR-TB. Personalization of the duration of
      treatment for TB, especially for patients with M/XDR-TB, would be highly desired.
      Until recently there has been little interest in the identification of
      biosignatures that could eventually lead to individual recommendations for the
      duration of anti-TB therapy. This pulmonary perspective reviews the knowledge on
      clinical and radiological scores, host- and pathogen disease-related profiles,
      molecules, and signatures that are currently explored as biomarkers to
      personalize the duration of therapy in TB. 

PMID- 24941307
TI  - Stimulated bacterial growth under elevated p CO2: results from an off-shore
      mesocosm study.
AB  - Marine bacteria are the main consumers of freshly produced organic matter. Many
      enzymatic processes involved in the bacterial digestion of organic compounds were
      shown to be pH sensitive in previous studies. Due to the continuous rise in
      atmospheric CO2 concentration, seawater pH is presently decreasing at a rate
      unprecedented during the last 300 million years but the consequences for
      microbial physiology, organic matter cycling and marine biogeochemistry are still
      unresolved. We studied the effects of elevated seawater pCO2 on a natural
      plankton community during a large-scale mesocosm study in a Norwegian fjord. Nine
      Kiel Off-Shore Mesocosms for Future Ocean Simulations (KOSMOS) were adjusted to
      different pCO2 levels ranging initially from ca. 280 to 3000 uatm and sampled
      every second day for 34 days. The first phytoplankton bloom developed around day
      5. On day 14, inorganic nutrients were added to the enclosed, nutrient-poor
      waters to stimulate a second phytoplankton bloom, which occurred around day 20.
      Our results indicate that marine bacteria benefit directly and indirectly from
      decreasing seawater pH. During the first phytoplankton bloom, 5-10% more
      transparent exopolymer particles were formed in the high pCO2 mesocosms.
      Simultaneously, the efficiency of the protein-degrading enzyme leucine
      aminopeptidase increased with decreasing pH resulting in up to three times higher
      values in the highest pCO2/lowest pH mesocosm compared to the controls. In
      general, total and cell-specific aminopeptidase activities were elevated under
      low pH conditions. The combination of enhanced enzymatic hydrolysis of organic
      matter and increased availability of gel particles as substrate supported up to
      28% higher bacterial abundance in the high pCO2 treatments. We conclude that
      ocean acidification has the potential to stimulate the bacterial community and
      facilitate the microbial recycling of freshly produced organic matter, thus
      strengthening the role of the microbial loop in the surface ocean. 

PMID- 24941308
TI  - Directional wetting in anisotropic inverse opals.
AB  - Porous materials display interesting transport phenomena due to restricted motion
      of fluids within the nano- to microscale voids. Here, we investigate how liquid
      wetting in highly ordered inverse opals is affected by anisotropy in pore
      geometry. We compare samples with different degrees of pore asphericity and find
      different wetting patterns depending on the pore shape. Highly anisotropic
      structures are infiltrated more easily than their isotropic counterparts.
      Further, the wetting of anisotropic inverse opals is directional, with liquids
      filling from the side more easily. This effect is supported by percolation
      simulations as well as direct observations of wetting using time-resolved optical
      microscopy. 

PMID- 24941310
TI  - Tucker.

PMID- 24941311
TI  - Model-Based Optimal Design and Execution of the First-Inpatient Trial of the Anti
      IL-6, Olokizumab.
AB  - The first-in-patient study for olokizumab (OKZ) employed model-based, optimal
      design and adaptive execution to define the concentration-C-reactive protein
      (CRP) suppression response. Modeling and exploratory statistics activities
      involved: reverse engineering of first-in-class (tocilizumab)
      pharmacokinetic/pharmacodynamic (PK/PD) models, adaptation of models to OKZ with
      a priori knowledge and preclinical data translation, application of
      multidimensional Desirability Index for optimal study design, sample size
      reestimation based on new information, optimization of second study part via
      Bayesian analysis of interim data, and interim and final analysis for PK/PD
      objective attainment. Design work defined a dose window (0.1-3 mg/kg) for CRP
      suppression exploration and suggested 72 patients in five single-dose levels
      would suffice. During execution, new information resulted in reestimating the
      study size to half. Halting the first part and conducting interim analysis for
      second part optimization followed. Second interim and final analyses confirmed
      attainment of study objective, illustrating efficiency and optimality of the
      study. 

PMID- 24941309
TI  - Cloning, expression and characterization of UDP-N-acetylglucosamine enolpyruvyl
      transferase (MurA) from Wolbachia endosymbiont of human lymphatic filarial
      parasite Brugia malayi.
AB  - Wolbachia, an endosymbiont of filarial nematode, is considered a promising target
      for treatment of lymphatic filariasis. Although functional characterization of
      the Wolbachia peptidoglycan assembly has not been fully explored, the Wolbachia
      genome provides evidence for coding all of the genes involved in lipid II
      biosynthesis, a part of peptidoglycan biosynthesis pathway. UDP-N
      acetylglucosamine enolpyruvyl transferase (MurA) is one of the lipid II
      biosynthesis pathway enzymes and it has inevitably been recognized as an
      antibiotic target. In view of the vital role of MurA in bacterial viability and
      survival, MurA ortholog from Wolbachia endosymbiont of Brugia malayi (wBm-MurA)
      was cloned, expressed and purified for further molecular characterization. The
      enzyme kinetics and inhibition studies were undertaken using fosfomycin. wBm-MurA
      was found to be expressed in all the major life stages of B. malayi and was
      immunolocalized in Wolbachia within the microfilariae and female adults by the
      confocal microscopy. Sequence analysis suggests that the amino acids crucial for
      enzymatic activity are conserved. The purified wBm-MurA was shown to possess the
      EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase) like activity at a
      broad pH range with optimal activity at pH 7.5 and 37 degrees C temperature. The
      apparent affinity constant (Km) for the substrate UDP-N-acetylglucosamine was
      found to be 0.03149 mM and for phosphoenolpyruvate 0.009198 mM. The relative
      enzymatic activity was inhibited ~2 fold in presence of fosfomycin.
      Superimposition of the wBm-MurA homology model with the structural model of
      Haemophilus influenzae (Hi-MurA) suggests binding of fosfomycin at the same
      active site. The findings suggest wBm-MurA to be a putative antifilarial drug
      target for screening of novel compounds. 

PMID- 24941312
TI  - All-optical tuning of a magnetic-fluid-filled optofluidic ring resonator.
AB  - An all-optical tunable optofluidic ring resonator (OFRR) is proposed and
      experimentally demonstrated. The all-optical control of a silica microresonator
      is highly attractive, but it is difficult to realize because of the relatively
      weak Kerr effect and the absence of a plasma dispersion effect of silica. Here,
      we infuse a silica microcapillary-based optofluidic ring resonator with a
      magnetic fluid, into which pump light is injected by a fiber taper. Iron oxide
      nanoparticles dispersed in the magnetic fluid produce a strong pump light
      absorption, and this leads to a resonance shift of the silica microresonator due
      to the photothermal effect. To the best of our knowledge, this is the first
      scheme for all-optical tuning of an OFRR. A tuning sensitivity of up to 0.15 nm
      mW(-1) and a tuning range of 3.3 nm are achieved. With such excellent
      performance, the magnetic-fluid-filled OFRR has great potential in filtering,
      sensing, and signal processing applications. 

PMID- 24941314
TI  - Regulation of Dendritic Cell Function by Dietary Polyphenols.
AB  - Marked changes in socioeconomic status, cultural traditions, population growth,
      and agriculture have been affecting diets worldwide. Nutrition is known to play a
      pivotal role in the pathogenesis of several chronic diseases, and the use of
      bioactive food compounds at pharmacologic doses is emerging as a preventive
      and/or therapeutic approach to target metabolic dysregulations occurring in
      aging, obesity-related chronic diseases, and cancer. Only recently have data on
      the effects of specific nutrients or food on the immune system become available,
      and studies regarding the human immune system are still in their infancy. Beyond
      providing essential nutrients, diet can actively influence the immune system.
      Understanding how diet and nutritional status influence the innate and adaptive
      arms of our immune system represents an area of scientific need, opportunity, and
      challenge. The insights gleaned should help to address several pressing global
      health problems. Recently, biologically active polyphenols, which are widespread
      constituents of fruit and vegetables, have gained importance as complex
      regulators of various cellular processes, critically involved in the maintenance
      of body homeostasis. This review outlines the potential effects of polyphenols on
      the function of dendritic cells (DCs), key players in the orchestration of the
      immune response. Their effects on different aspects of DC biology including
      differentiation, maturation, and DC capacity to shift immune response toward
      tolerance or immune activation will be outlined. 

PMID- 24941313
TI  - 1-Dodecyl-3-methylimidazolium chloride-assisted sample preparation method for
      efficient integral membrane proteome analysis.
AB  - Due to their extremely hydrophobic nature, the analysis of integral membrane
      proteins (IMPs) is of great challenge. Although various additives have been
      applied to improve the solubility of IMPs, they still suffer from low
      solubilization efficiency, incompatibility with trypsin digestion, or
      interference with MS detection. Herein, the systematic study on the effect of
      ionic liquid structure on membrane protein solubilization and trypsin
      biocompatibility was performed, based on which 1-dodecyl-3-methylimidazolium
      chloride (C12Im-Cl) was selected for the sample preparation of IMPs. Compared
      with other commonly used additives, such as sodium dodecyl sulfate (SDS),
      Rapigest, and methanol, C12Im-Cl showed the best performance. In addition, with a
      strong cation exchange trap column, it could be easily removed after trypsin
      digestion, which not only was beneficial to avoid protein precipitation during
      digestion but also had no adverse effect on LC-MS-based separation and detection.
      Such a C12Im-Cl-assisted sample preparation method was further applied to the
      membrane proteome analysis of rat brain. Compared with the SDS-assisted method,
      1.4 and 3.5 times improvement on the identified IMP and hydrophobic peptide
      number were achieved (251 vs 178, and 982 vs 279). All these results demonstrated
      that the C12Im-Cl-assisted sample preparation method is of great promise to
      promote the large-scale membrane proteome profiling. 

PMID- 24941315
TI  - Prescription medication use by Canadians aged 6 to 79.
AB  - Based on data from the 2007 to 2009 and 2009 to 2011 Canadian Health Measures
      Survey, this article provides national information about prescription medication
      use among community-dwelling Canadians. An estimated 41% of 6- to 79-year-olds
      who lived in private households reported taking at least one prescription
      medication in the past two days (current use). Generally, prescription drug use
      was higher among females and among people in poorer health, and increased with
      age. Approximately 11% of 45- to 64-year-olds and 30% of seniors aged 65 to 79
      took at least five prescription medications concurrently. For adults aged 25 to
      79, the leading prescription medication classes were lipid-lowering agents, ACE
      inhibitors, peptic-ulcer and acid-reducers, beta-blockers (men), other analgesics
      and anti-pyretics (men), anti-depressants (women) and thyroid medication (women).
      Among children and young adults aged 6 to 24, the leading prescription
      medications were for attention deficit and hyperactivity disorder (males),
      depression, and hormonal contraception (females). 

PMID- 24941316
TI  - Prevalence of migraine in the Canadian household population.
AB  - Based on data from the 2010 and 2011 Canadian Community Health Surveys and the
      2011 Survey of Living with Neurological Conditions in Canada, this article
      provides information about migraine among people living in private households. In
      2010/2011, an estimated 8.3% of Canadians (2.7 million) reported that they had
      been diagnosed with migraine by a health professional. Females were more likely
      than males to report migraine: 11.8% versus 4.7%. Migraine prevalence was highest
      among people in their 30s and 40s: 17.0% for women and 6.5% for men. Compared
      with the national figure, the prevalence of migraine was lower in Quebec (6.8%)
      and higher in Manitoba (9.5%), Nova Scotia (9.1%) and Ontario (8.8%). Among
      people who reported a migraine diagnosis, 42% took prescription medication for
      their condition, and 56% incurred medication-related out-of-pocket expenses.
      Migraine was highly comorbid with depression and affected many aspects of daily
      life including education, work, sleep, and driving. 

PMID- 24941317
TI  - Reproductive parameters in the critically endangered Blue-throated Macaw: limits
      to the recovery of a parrot under intensive management.
AB  - Rediscovered in the wild twenty years ago, the breeding biology of wild Blue
      throated Macaws remains largely unexplored, yet is essential to its effective
      conservation and recovery. Here, we analyse reproductive parameters in an
      intensively managed wild population of Blue-throated Macaws, providing the first
      data on the breeding biology of this critically endangered species. During the
      six-year study period, 2007-2012, the number of active breeding pairs either
      remained constant or decreased, depending on the site, and no new breeding pairs
      were discovered despite extensive searching. We documented nesting attempts in
      natural cavities in dead palms or live hardwoods, and artificial nest boxes. Egg
      laying was concentrated during the end of dry season and the beginning of the wet
      season, August through December. Hatching failure was the greatest cause of egg
      losses. Half of the breeding attempts of Blue-throated Macaws produced at least
      one fledging, on average two, after a 85 days nestling period. An average of 4.3
      nestlings per year fledged from all known wild nests combined. Each pair lost
      roughly 65% of its initial reproductive investment at each nesting attempt. In
      most successful nesting attempts of individualized pairs, a new nesting attempt
      was not detected the following year. All monitored breeding pairs showed high
      nest site fidelity, reusing hardwood-tree cavities and nest boxes. Our findings
      will aid conservation efforts by refining current actions and prompting new
      approaches towards the conservation and recovery of the Blue-throated Macaw. 

PMID- 24941320
TI  - Solid polymer films exhibiting handedness-switchable, full-color-tunable
      selective reflection of circularly polarized light.
AB  - Poly(quinoxaline-2,3-diyl)s bearing (S)-2-methylbutyl, n-butyl, and 8-chlorooctyl
      groups as side chains were synthesized to fabricate dry solid polymer thin films.
      These films exhibited selective reflection of right-handed circular polarized
      light (CPL) in the visible region after annealing in CHCl3 vapor at room
      temperature. The handedness of reflected CPL was inverted to the left after
      annealing in 1,2-dichloroethane vapor. It was also found that the color of a
      particular single film along with the handedness of reflected CPL were fully
      tuned reversibly, upon exposure of the film to the vapor of various mixtures of
      chloroform and 1,2-dichloroethane in different ratios. 

PMID- 24941319
TI  - Osmotic nephrosis with mannitol: review article.
AB  - Mannitol is commonly used to lower intracranial and intraocular pressures. Large
      doses/massive infusions of mannitol have been found to be associated with acute
      renal failure (MI-ARF), that is, osmotic nephrosis. While many researchers have
      reported individual experiences with this pathology, we felt that there is need
      of an updated comprehensive review of all reported cases with elaboration of
      etiology, pathogenesis, diagnosis and management plan for MI-ARF. The purpose of
      the present communication is to share our own experience with MI-ARF, to review
      the effect of mannitol on kidney function and to highlight the dynamics of MI-ARF
      with considerations for the cautious use of mannitol in patients with risk
      factors for kidney diseases.

PMID- 24941321
TI  - Amyloid fibrils enhance transport of metal nanoparticles in living cells and
      induced cytotoxicity.
AB  - Amyloid protein fibrils occur in vivo as pathological agents, in the case of
      neurodegenerative diseases, or as functional amyloids, when playing biologically
      vital roles. Here we show how amyloid fibrils generated from a food protein, beta
      lactoglobulin, can be used as nanoreactors for the synthesis of metal
      nanoparticles and demonstrate that the resulting hybrids can play a central role
      in the internalization of nanoparticles into living cells, with up to 3-fold
      enhanced transport properties over pristine nanoparticles. We conjugate gold,
      silver, and palladium nanoparticles onto amyloid fibrils by chemical reduction,
      and we study their effect on dendritic and MCF7 breast cancer cells. Transmission
      electron microscopy indicates localization of nanoparticles inside vesicles of
      the cells. Flow cytometry reveals that silver nanoparticle-amyloid hybrids are
      cytotoxic, while gold and palladium nanoparticle-amyloid hybrids produce no
      notable effect on cell viability and activation status. 

PMID- 24941322
TI  - MicroRNAs and ceRNAs: therapeutic implications of RNA networks.
AB  - INTRODUCTION: A new concept of gene regulation, in which competitive endogenous
      RNAs (ceRNAs) compete for common microRNAs (miRNAs), suggests that mRNA targets
      have an active role as key elements in the regulation of miRNA availability
      within cells. ceRNAs are considered to be natural decoys of miRNA activity and
      can influence the expression of multiple miRNAs. AREAS COVERED: A new complex
      network of indirect interaction among the RNA transcripts competing for the same
      pool of miRNAs has been described; in this network, the nodes are the targets,
      and the links between the nodes are the miRNAs the targets have in common, which
      form smaller subnetworks. The incidence, state and severity of cancer can be
      evaluated on the basis of this network signature. The study of these new genome
      scale regulatory networks involving miRNAs and ceRNAs may provide information
      that researchers can use to fine-tune these networks to improve responses to
      cancer therapy and/or develop new therapeutic interventions. EXPERT OPINION:
      Combinational approaches based on complex regulatory ceRNA networks (ceRNETs) may
      be one of the most promising strategies for silencing important mediators of
      cancer-promoting pathways. Targeting a single miRNA may in fact represent a
      combined intervention that acts on the feedback and compensatory pathways that
      can impair treatment response or cause treatment resistance.

PMID- 24941323
TI  - MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte
      apoptosis by targeting Smad7.
AB  - BACKGROUND: MicroRNAs (miRNAs) regulate a lot of physiological and pathological
      processes, including myocardial ischemia/reperfusion. Recent studies reported
      that knockdown of miR-92a could attenuate ischemia/reperfusion-induced myocardial
      injury. In the present study, we examined the potential anti-apoptotic effects of
      miR-92a in a rat myocardiocyte cell line, and the possible role of Smad7 in such
      actions. METHODOLOGY AND RESULTS: In a preliminary bioinformatic analysis, we
      identified SMAD family member 7 (Smad7) as a potential target for miR-92a. A
      luciferase reporter assay indeed demonstrated that miR-92a could inhibit Smad7
      expression. Myocardial ischemia/reperfusion was simulated in rat H9c2 cells with
      24-h hypoxia followed by 12-h reoxygenation. Prior to hypoxia/reoxygenation,
      cells were transfected by miR-92a inhibitor. In some experiments, cells were co
      transfected with siRNA-Smad7. The miR-92a inhibitor dramatically reduced the
      release of lactate dehydrogenase and malonaldehyde, and attenuated cardiomyocyte
      apoptosis. The miR-92a inhibitor increased SMAD7 protein level and decreased
      nuclear NF-kappaB p65 protein. Effects of the miR-92a inhibitor were attenuated
      by co-transfection with siRNA-Smad7. CONCLUSION: Inhibiting miR-92a can attenuate
      myocardiocyte apoptosis induced by hypoxia/reoxygenation by targeting Smad7.

PMID- 24941324
TI  - Reduced susceptibility of a Biomphalaria tenagophila population to Schistosoma
      mansoni after introducing the resistant Taim/RS strain of B. tenagophila into
      Herivelton Martins stream.
AB  - Studies performed in the last 30 years demonstrated that a strain of B.
      tenagophila from the Taim Biological Reserve is completely resistant to
      Schistosoma mansoni infection. This resistance to parasite infection is a
      dominant characteristic during crossbreeding with susceptible B. tenagophila
      strains. These experiments also identified a 350 bp molecular marker that is
      exclusive to the Taim strain and does not occur in other geographic strains of
      this snail species. The Taim strain (Taim/RS) of Biomphalaria tenagophila was
      bred on a large scale, physically marked and introduced into a stream in which
      previous malacological analyses had revealed the presence of only parasite
      susceptible B. tenagophila. Samples of offspring captured 4, 11 and 14 months
      after the introduction of the Taim strain were examined, and the susceptibility
      of the snails to S. mansoni infection dropped from 38.6-26.5% to 2.1% during the
      14 months after the introduction of the Taim snail strain. A significant
      correlation was also observed between the absence of infection and the
      identification of the Taim molecular marker. These results demonstrate that the
      genetic marker from the Taim strain was successfully introduced into the wild
      snail population. In addition, a significant relationship exists between the
      marker and resistance to infection. 

PMID- 24941326
TI  - Synergistic Effect of Dazomet Soil Fumigation and Clonostachys rosea Against
      Cucumber Fusarium Wilt.
AB  - Soil fumigation and biological control are two control measures frequently used
      against soilborne diseases. In this study, the chemical fumigant dazomet was
      applied in combination with the biocontrol agent (BCA) Clonostachys rosea 67-1 to
      combat cucumber wilt caused by Fusarium oxysporum f. sp. cucumerinum KW2-1. When
      the mycoparasite C. rosea 67-1 was applied after dazomet fumigation, disease
      control reached 100%, compared with 88.1 and 69.8% for dazomet and 67-1 agent,
      respectively, applied alone, indicating a synergistic effect of dazomet and C.
      rosea in combating cucumber Fusarium wilt based on analysis of Bliss
      Independence. To understand the synergistic mechanism, the effects of chemical
      fumigation on the colonization potential and activity of F. oxysporum f. sp.
      cucumerinum, and the interaction between the BCA and the pathogen were
      investigated. The results showed that growth of the pathogen decreased with
      increasing dazomet concentration subsequent to fumigation. When exposed to
      dazomet at 100 ppm, the fungal sporulation rate decreased by 94.4%. Severe damage
      was observed in fumigated isolates using scanning electron microscopy. In the
      greenhouse, disease incidence of cucumber caused by fumigated F. oxysporum f. sp.
      cucumerinum significantly decreased. Whereas germination of C. rosea 67-1 spores
      increased by >sixfold in fumigated soil, and its ability to parasitize fumigated
      F. oxysporum f. sp. cucumerinum significantly increased (P = 0.014).

PMID- 24941328
TI  - Abscisic Acid-Cytokinin Antagonism Modulates Resistance Against Pseudomonas
      syringae in Tobacco.
AB  - Phytohormones are known as essential regulators of plant defenses, with ethylene,
      jasmonic acid, and salicylic acid as the central immunity backbone, while other
      phytohormones have been demonstrated to interact with this. Only recently, a
      function of the classic phytohormone cytokinin in plant immunity has been
      described in Arabidopsis, rice, and tobacco. Although interactions of cytokinins
      with salicylic acid and auxin have been indicated, the complete network of
      cytokinin interactions with other immunity-relevant phytohormones is not yet
      understood. Therefore, we studied the interaction of kinetin and abscisic acid as
      a negative regulator of plant immunity to modulate resistance in tobacco against
      Pseudomonas syringae. By analyzing infection symptoms, pathogen proliferation,
      and accumulation of the phytoalexin scopoletin as a key mediator of kinetin
      induced resistance in tobacco, antagonistic interaction of these phytohormones in
      plant immunity was identified. Kinetin reduced abscisic acid levels in tobacco,
      while increased abscisic acid levels by exogenous application or inhibition of
      abscisic acid catabolism by diniconazole neutralized kinetin-induced resistance.
      Based on these results, we conclude that reduction of abscisic acid levels by
      enhanced abscisic acid catabolism strongly contributes to cytokinin-mediated
      resistance effects. Thus, the identified cytokinin-abscisic acid antagonism is a
      novel regulatory mechanism in plant immunity.

PMID- 24941327
TI  - Potential of Pseudomonas chlororaphis subsp. aurantiaca Strain Pcho10 as a
      Biocontrol Agent Against Fusarium graminearum.
AB  - To develop an effective biocontrol strategy for management of Fusarium head
      blight on wheat caused by Fusarium graminearum, the bacterial biocontrol agent
      Pcho10 was selected from more than 1,476 wheat-head-associated bacterial strains
      according to its antagonistic activity in vitro. This strain was subsequently
      characterized as Pseudomonas chlororaphis subsp. aurantiaca based on 16S
      ribosomal DNA sequence analysis, assays of the BIOLOG microbial identification
      system, and unique pigment production. The major antifungal metabolite produced
      by Pcho10 was further identified as phenazine-1-carboxamide (PCN) on the basis of
      nuclear magnetic resonance data. The core PCN biosynthesis gene cluster in Pcho10
      was cloned and sequenced. PCN showed strong inhibitory activity against F.
      graminearum conidial germination, mycelial growth, and deoxynivalenol production.
      Tests both under growth chamber conditions and in field trials showed that Pcho10
      well colonized on the wheat head and effectively controlled the disease caused by
      F. graminearum. Results of this study indicate that P. chlororaphis subsp.
      aurantiaca Pcho10 has high potential to be developed as a biocontrol agent
      against F. graminearum. To our knowledge, this is the first report of the use of
      P. chlororaphis for the management of Fusarium head blight.

PMID- 24941329
TI  - Lipoxygenase Activation in Peanut Seed Cultivars Resistant and Susceptible to
      Aspergillus parasiticus Colonization.
AB  - Accumulative evidence indicates that the lipoxygenase (LOX) pathway plays a
      significant role in the Aspergillus-seed interaction, such as interfering with
      activities of endogenous fungal oxylipins or producing antimicrobial compounds
      and signaling molecules. In this study, we characterized the LOX pathway in
      peanut seed during Aspergillus parasiticus colonization in a model of two
      cultivars distinguished as resistant ('PI337394') and susceptible ('Florman
      INTA') to Aspergillus spp. infection and aflatoxin contamination. The LOX
      activity together with the content of LOX substrate and LOX products demonstrated
      the presence of a differential response mechanism to A. parasiticus infection
      between cultivars. Our findings suggest that this mechanism is under
      transcriptional control of previously identified (LOX 2 and LOX 3) and novel (LOX
      4 and LOX 5) LOX genes. The results of this study support the role of these
      enzymes in defense during fungus infection in peanut seed.

PMID- 24941330
TI  - Fully integrated CMOS microsystem for electrochemical measurements on 32 * 32
      working electrodes at 90 frames per second.
AB  - Microelectrode arrays offer the potential to electrochemically monitor
      concentrations of molecules at high spatial resolution. However, current systems
      are limited in the number of sensor sites, signal resolution, and throughput.
      Here, we present a fully integrated complementary metal oxide semiconductor
      (CMOS) system with an array of 32 * 32 working electrodes to perform
      electrochemical measurements like amperometry and voltammetry. The array consists
      of platinum electrodes with a center-to-center distance of 100 MUm and electrode
      diameters of 5 to 50 MUm. Currents in the range from 10 MUA down to pA can be
      measured. The current is digitized by sigma-delta converters at a maximum
      resolution of 13.3 bits. The integrated noise is 220 fA for a bandwidth of 100
      Hz, allowing for detection of pA currents. Currents can be continuously acquired
      at up to 1 kHz bandwidth, or the whole array can be read out rapidly at a frame
      rate of up to 90 Hz. The results of the electrical characterization meet the
      requirements of a wide range of electrochemical methods including cyclic
      voltammograms and amperometric images of high spatial and temporal resolution. 

PMID- 24941331
TI  - West nile virus and other arboviral diseases - United States, 2013.
AB  - Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through
      the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading
      cause of domestically acquired arboviral disease in the United States. However,
      several other arboviruses also cause sporadic cases and seasonal outbreaks of
      neuroinvasive disease (i.e., meningitis, encephalitis, and acute flaccid
      paralysis). This report summarizes surveillance data reported to CDC in 2013 for
      WNV and other nationally notifiable arboviruses, excluding dengue. Forty-seven
      states and the District of Columbia reported 2,469 cases of WNV disease. Of
      these, 1,267 (51%) were classified as WNV neuroinvasive disease, for a national
      incidence of 0.40 per 100,000 population. After WNV, the next most commonly
      reported cause of arboviral disease was La Crosse virus (LACV) (85 cases),
      followed by Jamestown Canyon virus (JCV), Powassan virus (POWV), and eastern
      equine encephalitis virus (EEEV) (eight). WNV and other arboviruses continue to
      cause serious illness in substantial numbers of persons annually. Maintaining
      surveillance remains important to help direct and promote prevention activities. 

PMID- 24941332
TI  - Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk
      for meningococcal disease: recommendations of the Advisory Committee on
      Immunization Practices, 2013.
AB  - During its October 2013 meeting, the Advisory Committee on Immunization Practices
      (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM
      (Menveo, Novartis), as an additional option for vaccinating infants aged 2
      through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the
      first quadrivalent meningococcal conjugate vaccine licensed for use in children
      aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for
      use in children aged 9 through 23 months who are at increased risk for
      meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is
      recommended for use in children aged 6 weeks through 18 months at increased risk.
      This report summarizes information on MenACWY-CRM administration in infants and
      provides recommendations for vaccine use in infants aged 2 through 23 months who
      are at increased risk for meningococcal disease. Because the burden of
      meningococcal disease in infants is low in the United States and the majority of
      cases that do occur are caused by serogroup B, which is not included in any
      vaccine licensed in the United States, only those infants who are at increased
      risk for meningococcal disease are recommended to receive a meningococcal
      vaccine. 

PMID- 24941333
TI  - Notes from the field: increase in fentanyl-related overdose deaths - Rhode
      Island, November 2013-March 2014.
AB  - During November 2013-March 2014, twice as many all-intent drug overdose deaths
      were reported in Rhode Island as were reported during the same period in previous
      years. Most deaths were among injection-drug users, and a large percentage
      involved fentanyl, a synthetic opioid that is 50-100 times more potent than
      morphine. Clusters of fentanyl-related deaths have been reported recently in
      several states. From April 2005 to March 2007, time-limited active surveillance
      from CDC and the Drug Enforcement Administration identified 1,013 deaths caused
      by illicit fentanyl use in New Jersey; Maryland; Chicago, Illinois; Detroit,
      Michigan; and Philadelphia, Pennsylvania. Acetyl fentanyl, an illegally produced
      fentanyl analog, caused a cluster of overdose deaths in northern Rhode Island in
      2013. 

PMID- 24941335
TI  - The effect of micro-ECoG substrate footprint on the meningeal tissue response.
AB  - OBJECTIVE: There is great interest in designing implantable neural electrode
      arrays that maximize function while minimizing tissue effects and damage.
      Although it has been shown that substrate geometry plays a key role in the tissue
      response to intracortically implanted, penetrating neural interfaces, there has
      been minimal investigation into the effect of substrate footprint on the tissue
      response to surface electrode arrays. This study investigates the effect of micro
      electrocorticography (micro-ECoG) device geometry on the longitudinal tissue
      response. APPROACH: The meningeal tissue response to two micro-ECoG devices with
      differing geometries was evaluated. The first device had each electrode site and
      trace individually insulated, with open regions in between, while the second
      device had a solid substrate, in which all 16 electrode sites were embedded in a
      continuous insulating sheet. These devices were implanted bilaterally in rats,
      beneath cranial windows, through which the meningeal tissue response was
      monitored for one month after implantation. Electrode site impedance spectra were
      also monitored during the implantation period. MAIN RESULTS: It was observed that
      collagenous scar tissue formed around both types of devices. However, the
      distribution of the tissue growth was different between the two array designs.
      The mesh devices experienced thick tissue growth between the device and the
      cranial window, and minimal tissue growth between the device and the brain, while
      the solid device showed the opposite effect, with thick tissue forming between
      the brain and the electrode sites. SIGNIFICANCE: These data suggest that an open
      architecture device would be more ideal for neural recording applications, in
      which a low impedance path from the brain to the electrode sites is critical for
      maximum recording quality.

PMID- 24941336
TI  - The impact and cost of scaling up midwifery and obstetrics in 58 low- and middle
      income countries.
AB  - BACKGROUND AND METHODS: To guide achievement of the Millennium Development Goals,
      we used the Lives Saved Tool to provide a novel simulation of potential maternal,
      fetal, and newborn lives and costs saved by scaling up midwifery and obstetrics
      services, including family planning, in 58 low- and middle-income countries.
      Typical midwifery and obstetrics interventions were scaled to either 60% of the
      national population (modest coverage) or 99% (universal coverage). FINDINGS:
      Under even a modest scale-up, midwifery services including family planning reduce
      maternal, fetal, and neonatal deaths by 34%. Increasing midwifery alone or
      integrated with obstetrics is more cost-effective than scaling up obstetrics
      alone; when family planning was included, the midwifery model was almost twice as
      cost-effective as the obstetrics model, at $2,200 versus $4,200 per death
      averted. The most effective strategy was the most comprehensive: increasing
      midwives, obstetricians, and family planning could prevent 69% of total deaths
      under universal scale-up, yielding a cost per death prevented of just $2,100.
      Within this analysis, the interventions which midwifery and obstetrics are poised
      to deliver most effectively are different, with midwifery benefits delivered
      across the continuum of pre-pregnancy, prenatal, labor and delivery, and
      postpartum-postnatal care, and obstetrics benefits focused mostly on delivery.
      Including family planning within each scope of practice reduced the number of
      likely births, and thus deaths, and increased the cost-effectiveness of the
      entire package (e.g., a 52% reduction in deaths with midwifery and obstetrics
      increased to 69% when family planning was added; cost decreased from $4,000 to
      $2,100 per death averted). CONCLUSIONS: This analysis suggests that scaling up
      midwifery and obstetrics could bring many countries closer to achieving mortality
      reductions. Midwives alone can achieve remarkable mortality reductions,
      particularly when they also perform family planning services--the greatest return
      on investment occurs with the scale-up of midwives and obstetricians together.

PMID- 24941337
TI  - S-Glutathionylation at Cys328 and Cys542 impairs STAT3 phosphorylation.
AB  - STAT3 is a latent transcription factor that promotes cell survival and
      proliferation and is often constitutively active in cancers. Although many
      reports provide evidence that STAT3 is a direct target of oxidative stress, its
      redox regulation is poorly understood. Under oxidative conditions STAT3 activity
      can be modulated by S-glutathionylation, a reversible redox modification of
      cysteine residues. This suggests the possible cross-talk between phosphorylation
      and glutathionylation and points out that STAT3 is susceptible to redox
      regulation. Recently, we reported that decreasing the GSH content in different
      cell lines induces inhibition of STAT3 activity through the reversible oxidation
      of thiol groups. In the present work, we demonstrate that GSH/diamide treatment
      induces S-glutathionylation of STAT3 in the recombinant purified form. This
      effect was completely reversed by treatment with the reducing agent
      dithiothreitol, indicating that S-glutathionylation of STAT3 was related to
      formation of protein-mixed disulfides. Moreover, addition of the bulky negatively
      charged GSH moiety impairs JAK2-mediated STAT3 phosphorylation, very likely
      interfering with tyrosine accessibility and thus affecting protein structure and
      function. Mass mapping analysis identifies two glutathionylated cysteine
      residues, Cys328 and Cys542, within the DNA-binding domain and the linker domain,
      respectively. Site direct mutagenesis and in vitro kinase assay confirm the
      importance of both cysteine residues in the complex redox regulatory mechanism of
      STAT3. Cells expressing mutant were resistant in this regard. The data presented
      herein confirmed the occurrence of a redox-dependent regulation of STAT3,
      identified the more redox-sensitive cysteines within STAT3 structure, and may
      have important implications for development of new drugs. 

PMID- 24941338
TI  - Ethyl ferulate, a component with anti-inflammatory properties for emulsion-based
      creams.
AB  - Ethyl ferulate (FAEE) has been widely studied due to its beneficial heath
      properties and, when incorporated in creams, shows a high sun protection
      capacity. Here we aimed to compare FAEE and its precursor, ferulic acid (FA), as
      free radical scavengers, inhibitors of oxidants produced by leukocytes and the
      alterations in rheological properties when incorporated in emulsion based creams.
      The cell-free antiradical capacity of FAEE was decreased compared to FA. However,
      FAEE was more effective regarding the scavenging of reactive oxygen species
      produced by activated leukocytes. Stress and frequency sweep tests showed that
      the formulations are more elastic than viscous. The viscoelastic features of the
      formulations were confirmed in the creep and recovery assay and showed that the
      FAEE formulation was less susceptive to deformation. Liberation experiments
      showed that the rate of FAEE release from the emulsion was slower compared to FA.
      In conclusion, FAEE is more effective than FA as a potential inhibitor of
      oxidative damage produced by oxidants generated by leukocytes. The rheological
      alterations caused by the addition of FAEE are indicative of lower spreadability,
      which could be useful for formulations used in restricted areas of the skin. 

PMID- 24941339
TI  - Synthesis and fungicidal activity of novel chloro-containing 1-aryl-3
      oxypyrazoles with an oximino ester or oximino amide moiety.
AB  - Six novel chloro-containing 1-aryl-3-oxypyrazoles TMa-TMf with an oximino ester
      or an oximino amide moiety were prepared by the reaction of 1-aryl-1H-pyrazol-3
      ols with benzyl bromide. Their structures were characterized by 1H-NMR, 13C-NMR,
      IR, MS, and elemental analysis. A preliminary in vitro bioassay indicated that
      compounds TMa, TMe and TMf displayed excellent fungicidal activity against
      Rhizoctonia solani and could be used as potential lead compounds for further
      development of novel fungicides. 

PMID- 24941340
TI  - Natural products as source of potential dengue antivirals.
AB  - Dengue is a neglected disease responsible for 22,000 deaths each year in areas
      where it is endemic. To date, there is no clinically approved dengue vaccine or
      antiviral for human beings, even though there have been great efforts to
      accomplish these goals. Several approaches have been used in the search for
      dengue antivirals such as screening of compounds against dengue virus enzymes and
      structure-based computational discovery. During the last decades, researchers
      have turned their attention to nature, trying to identify compounds that can be
      used as dengue antivirals. Nature represents a vast reservoir of substances that
      can be explored with the aim of discovering new leads that can be either used
      directly as pharmaceuticals or can serve as lead structures that can be optimized
      towards the development of new antiviral agents against dengue. In this review we
      describe an assortment of natural products that have been reported as possessing
      dengue antiviral activity. The natural products are organized into classes of
      substances. When appropriate, structure-activity relationships are outlined. The
      biological assays used to assess antiviral activity are briefly described. 

PMID- 24941341
TI  - Influence of temperature and preserving agents on the stability of cornelian
      cherries anthocyanins.
AB  - Cornelian cherry (Cornus mas L.) fruits are known for their significant amounts
      of anthocyanins which can be used as natural food colorants. The storage
      stability of anthocyanins from these fruit extracts, at different temperatures (2
      degrees C, 25  degrees C and 75  degrees C), pH 3.02, in the presence of two of
      the most widely employed food preserving agents (sodium benzoate and potassium
      sorbate) was investigated. The highest stability was exhibited by the anthocyanin
      extract stored at 2  degrees C without any added preservative, with half-life and
      constant rate values of 1443.8 h and 0.48 * 10(-3) h(-1), respectively. The
      highest value of the degradation rate constant (82.76 * 10(-3)/h) was obtained in
      the case of anthocyanin extract stored at 75  degrees C without any added
      preservative. Experimental results indicate that the storage degradation of
      anthocyanins followed first-order reaction kinetics under each of the
      investigated conditions. In aqueous solution, the food preservatives used were
      found to have a slight influence on the anthocyanins' stability.

PMID- 24941342
TI  - Standardized Salvia miltiorrhiza extract suppresses hepatic stellate cell
      activation and attenuates steatohepatitis induced by a methionine-choline
      deficient diet in mice.
AB  - The aim of this study was to examine the effect of standardized extract of Salvia
      miltiorrhiza (SME) on gene and protein expression of non-alcoholic
      steatohepatitis (NASH)-related factors in activated human hepatic stellate cells
      (HSC), and in mice with steatohepatitis induced by a methionine-choline deficient
      (MCD) diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks
      and SME (0, 0.1, 0.5 and 1 mg/kg body weight) was administered orally every other
      day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming
      growth factor beta-1 (TGF-beta1) or TGF-beta1 plus SME (0.1-10 MUg/mL). To
      investigate the effect of SME on reactive oxygen species (ROS)-induced condition,
      LX-2 cells were treated with hydrogen peroxide (H2O2) or H2O2 plus SME (0.1-100
      MUg/mL). MCD administration for 12 weeks increased mRNA expression of tumor
      necrosis factor (TNF-alpha), TGF-beta1, interleukin-1beta (IL-1beta), C-reactive
      protein (CRP), alpha-smooth muscle actin (alpha-SMA), type I collagen, matrix
      metalloproteinase-2 (MMP-2) and MMP-9. TGF-beta1-induced LX-2 cells exhibited
      similar gene expression patterns. SME treatment significantly reduced the mRNA
      and protein expression of NASH-related factors in the mouse model and HSCs.
      Histopathological liver analysis showed improved non-alcoholic fatty liver
      disease (NAFLD) activity and fibrosis score in SME-treated mice. The in vivo
      studies showed that SME had a significant effect at low doses. These results
      suggest that SME might be a potential therapeutic candidate for NAFLD treatment. 

PMID- 24941343
TI  - Inhibitory activity of the flower buds of Lonicera japonica Thunb. against
      histamine production and L-histidine decarboxylase in human keratinocytes.
AB  - In previous studies we found that anionic surfactants such as sodium laurate (SL)
      and/or sodium dodecylsulfate (SDS) exert actions on epidermal keratinocytes
      rather than mast cells to give rise of histamine production and skin itching
      through increasing the expression of the 53-kDa active form of L-histidine
      decarboxylase (HDC). In addition, with treatment of SL in a three-dimensional
      human keratinocyte culture, increases in both the 53-kDa HDC and histamine
      production are detected and thus this culture assay is applied to screen anti
      itching materials from natural resources. In this study, the inhibitory activity
      of "Kin-gin-ka" (flower buds of Lonicera japonica Thunb., FLJ) against histamine
      production and expression of the active form of HDC were examined in this culture
      assay. FLJ is a well-known traditional Chinese medicine, being used to treat
      fevers, coughs and some infectious diseases. The result showed both FLJ and
      chlorogenic acid had inhibitory activities against the expression of 53-kDa HDC
      and histamine production. However, chlorogenic acid showed a weaker effect on
      histamine production than that of FLJ, suggesting that other chemical
      constituents besides chlorogenic acid could contribute to the inhibitory
      activities. Thus, a further chemical study of FLJ is now under investigation.

PMID- 24941344
TI  - miRNAs as non-invasive biomarkers for lung cancer diagnosis.
AB  - Lung cancer is a leading cause of cancer death and late diagnosis is one of the
      most important reasons for the high mortality rate. Circulating microRNAs
      (miRNAs) represent stable and reproducible markers for numerous solid tumors,
      including lung cancer, and have been hypothesized as non-invasive diagnostic
      markers. Serum, plasma or whole peripheral blood can be used as starting
      material, and several methodological approaches have been proposed to evaluate
      miRNA expression. The present review provides an in depth summary of current
      knowledge on circulating miRNAs in different types of biological samples used as
      diagnostic markers of lung cancer. We also evaluate the diagnostic accuracy of
      each miRNA or group of miRNAs in relation to the different housekeeping miRNAs
      used. Finally, the limitations and potential of miRNA analysis are discussed. 

PMID- 24941346
TI  - Anti-angiogenic effects of trabectedin (Yondelis; ET-743) on human breast cancer
      cells.
AB  - Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate
      Ecteinascidia turbinata, has been shown to have antitumor effects. In this study,
      we assessed the possible anti-angiogenic effects of trabectedin on human
      umbilical vein endothelial cells (HUVECs) and breast cancer cell lines. An XTT
      cell viability assay was used to determine cytotoxicity. A scratch assay was used
      to detect the migration of cells after trabectedin treatment. Angiogenic cytokine
      profiles of breast cancer cell lines, before and after treatment with
      trabectedin, were investigated using an angiogenesis antibody array. Changes in
      mRNA expression levels of VEGF were evaluated using qRT-PCR. Trabectedin
      inhibited the viability of HUVECs and breast cancer cells in a concentration- and
      time-dependent manner. The migration of both HUVECs and breast cancer cells was
      suppressed by trabectedin treatment. Angiogenic cytokines which are known to
      regulate tumorigenicity and angiogenesis, such as GM-CSF, IGFBP-2, VEGF, and uPA,
      were inhibited, while several anti-angiogenic cytokines such as TIMP-1 and Serpin
      E1were induced in breast cancer cells. Furthermore, expression levels of VEGF
      mRNA were inhibited in all breast cancer cells tested. Although additional
      studies are needed to elucidate the molecular mechanisms underlying the anti
      angiogenic activity of trabectedin, our results suggest that trabectedin may act
      as a potential anti-angiogenic agent in breast cancer cells. 

PMID- 24941345
TI  - Failure of miltefosine treatment for visceral leishmaniasis in children and men
      in South-East Asia.
AB  - BACKGROUND: High frequency of relapse in miltefosine-treated visceral
      leishmaniasis (VL) patients in India and Nepal followed up for twelve months.
      OBJECTIVE: To identify epidemiological and clinical risk factors for relapse of
      VL in patients recently treated with standard dosing of miltefosine in India and
      Nepal. DESIGN: Prospective observational study in three Primary Health Centers
      and one reference center in Muzaffarpur district, Bihar, India; and two zonal
      hospitals and a university hospital in South-east Nepal; records of all
      consenting patients diagnosed with VL and treated with miltefosine according to
      the current treatment guidelines of the Kala azar elimination program between
      2009 and 2011. RESULTS: We compared the clinical records of 78 cases of relapse
      with those of 775 patients who had no record of subsequent relapse. Relapse was 2
      times more common amongst male patients (IRR 2.14, 95% CI 1.27-3.61), and 2 to 3
      times more frequent in the age groups below 15 compared to the over 25 year olds
      (age 10 to 14: IRR 2.53; 95% CI 1.37-4.65 and Age 2 to 9: IRR 3.19; 95% CI 1.77
      5.77). History of earlier VL episodes, or specific clinical features at time of
      diagnosis such as duration of symptoms or spleen size were no predictors of
      relapse. CONCLUSIONS: Young age and male gender were associated with increased
      risk of VL relapse after miltefosine, suggesting that the mechanism of relapse is
      mainly host-related i.e. immunological factors and/or drug exposure
      (pharmacokinetics). The observed decrease in efficacy of miltefosine may be
      explained by the inclusion of younger patients compared to the earlier clinical
      trials, rather than by a decreased susceptibility of the parasite to miltefosine.
      Our findings highlight the importance of proper clinical trials in children,
      including pharmacokinetics, to determine the safety, efficacy, drug exposure and
      therapeutic response of new drugs in this age group.

PMID- 24941348
TI  - Effect of gum arabic on glucose levels and microbial short-chain fatty acid
      production in white rice porridge model and mixed grain porridge model.
AB  - White rice porridge and mixed grain porridge, which are often consumed in many
      countries, were used as two models to evaluate the effects of gum arabic on
      glucose levels and microbial short-chain fatty acids (SCFA). Gum arabic was
      incorporated into the two porridges individually. Apparent viscosity of the two
      porridges was significantly increased, and their glucose productions during
      gastrointestinal digestion were notably lowered (p < 0.05). Diffused glucose
      amount was significantly decreased after gum arabic addition (p < 0.05).
      Furthermore, blood glucose rise after oral administration of porridges in mice
      was considerably lowered after fortified with gum arabic (p < 0.05). Microbial
      SCFA production during in vitro fermentation of porridges was significantly
      increased after gum arabic addition, which may also have beneficial effects on
      reducing postprandial glycemic response. Therefore, gum arabic may be a helpful
      ingredient, which could be added in porridges to have benefits for the reduction
      of postprandial glycemic response. 

PMID- 24941347
TI  - TC-1 overexpression promotes cell proliferation in human non-small cell lung
      cancer that can be inhibited by PD173074.
AB  - Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in
      vertebrates and overexpressed in many kinds of tumors. However, its exact role
      and regulation mechanism in human non-small cell lung cancer (NSCLC) are still
      unclear. In the present study, we found that TC-1 is highly expressed in NSCLC
      and that its aberrant expression is strongly associated with NSCLC cell
      proliferation. Exogenous TC-1 overexpression promotes cell proliferation,
      accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC.
      The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle
      transition, and apoptosis resistance. Furthermore, we also demonstrated that
      PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the
      expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation
      in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC
      cell proliferation was eliminated in cells with TC-1 knockdown. These results
      suggest that PD173074 plays a significant role in TC-1 overexpression mediated
      NSCLC cell proliferation and may be a potential intervention target for the
      prevention of cell proliferation in NSCLC. 

PMID- 24941349
TI  - Clinical expression of lymphocytic duodenosis in "mild enteropathy" celiac
      disease and in functional gastrointestinal syndromes.
AB  - OBJECTIVE: Abnormally high number of duodenal intraepithelial lymphocytes is
      frequently found in many conditions including mild enteropathy celiac disease
      (CD) and functional gastrointestinal syndromes, but is unclear whether
      lymphocytosis affects the clinical phenotype particularly in functional
      syndromes. MATERIALS AND METHODS: We compared clinical characteristics of celiac
      patients with lymphocytic duodenosis and normal villous structure with those of
      patients with functional gastrointestinal syndromes with and without lymphocytic
      duodenosis. We retrospectively identified 3 cohorts among patients referred for
      suspected CD: (1) "CoelD", 135 patients (age 36 +/- 14 years) with mild
      enteropathy CD; (2) "LymD", 245 patients (38 +/- 12 years) with functional
      gastrointestinal syndromes and lymphocytic duodenosis; and (3) "NorD", 147
      patients (37 +/- 15 years) with functional syndromes and normal duodenal
      histology. RESULTS: Prevalence of gastrointestinal symptoms was similar in the
      three cohorts, but prevalence of extra-intestinal manifestations (42% vs. 27% vs.
      18%, p < 0.003) and of associated diseases (35% vs. 15% vs. 14%, p < 0.0001) was
      higher in "CoelD" than in "LymD" and "NorD", respectively. Prevalence of
      Helicobacter pylori infection was similar in the three cohorts. The proportion of
      patients with final diagnosis of irritable bowel syndrome-diarrhea (38% vs. 37%),
      dyspepsia (31% vs. 27%), functional pain (14% vs. 19%), and functional diarrhoea
      (14% vs. 11%) was virtually the same in the cohorts with (LymD) and without
      (NorD) lymphocytic duodenosis. CONCLUSIONS: Lymphocytic duodenosis has different
      clinical presentation in patients with mild enteropathy CD than those with
      functional gastrointestinal syndromes, and is not specific for any particular
      functional syndrome.

PMID- 24941350
TI  - Measuring fatigue in polio survivors: content comparison and reliability of the
      Fatigue Severity Scale and the Checklist Individual Strength.
AB  - OBJECTIVES: To compare the content of the Fatigue Severity Scale and the subscale
      "subjective experience of fatigue" of the Checklist Individual Strength, and (ii)
      to assess the reliability of both questionnaires in polio survivors. DESIGN:
      Repeated-measures at a 3-week interval. SUBJECTS: Consecutive series of 61 polio
      survivors. METHODS: Concepts contained in the questionnaire items were linked to
      the International Classification of Functioning, Disability and Health (ICF),
      using standardized linking rules. Reliability analyses included tests of internal
      consistency, test-retest reliability and measurement error. RESULTS:
      Questionnaires differed in the extent to which they measured other than fatigue
      related aspects of functioning (represented ICF components: "Body functions": 50%
      and 80%, "Activities and Participation": 30% and 0%, for the Fatigue Severity
      Scale and Checklist Individual Strength, respectively). Internal consistency and
      test-retest reliability were considered acceptable, while measurement error was
      large (Cronbach's alpha: 0.90 and 0.93, intraclass correlation coefficient: 0.80
      and 0.85, smallest detectable change: 28.7% and 29.4% for the Fatigue Severity
      Scale and Checklist Individual Strength, respectively). CONCLUSION: Considering
      the acceptable clinimetric properties, we conclude that both the Fatigue Severity
      Scale and the Checklist Individual Strength can be applied in research on post
      poliomyelitis syndrome when measuring fatigue. However, because the 2
      questionnaires differ in content they cannot be used interchangeably.

PMID- 24941351
TI  - Neonatal Anesthesia Neurotoxicity: A Review for Cleft and Craniofacial Surgeons.
AB  - There is growing evidence that the commonly used anesthetic agents cause some
      degree of damage to the early developing brain. The animal evidence for
      anesthetic neurotoxicity is compelling. Numerous confounders in human research
      prevent researchers from drawing definitive conclusions about the degree of risk.
      For every surgery, it should be assessed whether the benefits of an early
      surgical procedure justify a potential but unquantifiable risk of neurotoxicity
      of anesthetic agents. The timing and number of surgeries in our treatment
      protocols may need to be reevaluated to account for these potential risks.

PMID- 24941352
TI  - Stability of orofacial clefting rate in alberta, 1980-2011.
AB  - Objective : To determine the prevalence and trends of orofacial clefts in Alberta
      (Canada) over a 33-year period (1980 through 2011) and to determine whether the
      trends differ for subcategories of orofacial clefts for the period from 1997
      through 2011. Design : A prevalence study based on the Alberta Congenital
      Anomalies Surveillance System, which has multiple sources of ascertainment,
      capability of verification, and an upper age limit of 1 year. Inclusion : All
      live born and stillborn babies and fetal deaths less than 20 weeks' gestation
      (including terminations of pregnancy) born in Alberta of mothers who reside in
      Alberta. Results and Conclusions : Rates for cleft lip with or without cleft
      palate and cleft palate only have been very stable over the 33-year period (1980
      through 2011). These rates include all clefts (isolated, syndromes, recognizable
      conditions, chromosomal and multiple congenital anomalies). Ascertainment of
      fetal deaths less than 20 weeks' gestation began in 1997. There are trends for
      the 1997 through 2011 cohort with a marginally significant increase for cleft lip
      with or without cleft palate in the isolated category and a significant decrease
      for cleft palate, mainly in the associated groups. The impact of folic acid
      fortification and/or multivitamins/folic acid supplementation reports in the
      literature have shown no consensus with respect to a change in the prevalence of
      orofacial clefts. It is unclear whether folic acid fortification has had any
      impact in Alberta. 

PMID- 24941355
TI  - Editorial.

PMID- 24941354
TI  - Three Gorges Reservoir: density pump amplification of pollutant transport into
      tributaries.
AB  - The impoundment of the Three Gorges Reservoir (TGR) on the Yangtze River in China
      burdened its tributary backwaters with severe environmental problems.1 Confluence
      zones of reservoir tributaries with the Yangtze River main channel are main
      drivers of pollutant dynamics in the TGR2 and are thus keys to develop mitigation
      measures. Here, we show a novel experimental approach of spatiotemporal water
      quality analysis to trace water mass movements and identify pollutant transport
      pathways in reservoir water bodies. Our results show the movements of density
      currents in a major tributary backwater of the TGR. A huge interflow density
      current from the Yangtze River main channel transported its heavy metal carriage
      to the upstream reaches of the tributary backwater. Water from the upstream
      backwater moved counterwise and carried less but pollutant-enriched suspended
      sediments. This scenario illustrates the importance of confluence zone
      hydrodynamics for fates and pathways of pollutants through the widely unknown
      hydrodynamics of new reservoirs. 

PMID- 24941356
TI  - Comorbid anxiety and depression: illumination of a controversy.
AB  - Depression and anxiety frequently coexist in the same individual, either
      concurrently or at different times, and numerous studies show that the presence
      of an anxiety disorder is the single strongest risk factor for development of
      depression. When the two coexist simultaneously, either as diagnosed disorders or
      subsyndromal states, they may be viewed as mixed anxiety-depression or as
      comorbid syndromes, i.e. separate disorders occurring concurrently. Controversy
      continues over the nature of the relationship between depression and anxiety,
      some believing they are distinct, separate entities while others - now the
      majority - view them as overlapping syndromes that present at different points on
      a phenomenological and/or chronological continuum, and share a common
      neurobiology, the degree of overlap depending on whether each is described at the
      level of symptoms, syndrome or diagnosis. Community data likely underestimate
      true prevalence, since affected individuals frequently present in primary care
      with somatic, rather than psychological, complaints. Irrespective of the nature
      of the relationship, patients with both disorders experience significant
      vocational and interpersonal impairment, and more frequent recurrence, with
      greater likelihood of suicide, than individuals with single disorders. Various
      classes of antidepressant drugs offer symptom relief for these patients, the most
      selective of th SSRIs holding the greatest promise for sustained clinical
      improvement. Yet, the crucial parameter of successful pharmacotherapy seems to be
      the length of treatment, ensuring enhancement of the compromised neuroprotective
      and neuroplastic mechanisms. Further clarification of the relationship is a
      prerequisite for offering effective treatment to the many patients who experience
      lifetime depression and anxiety. 

PMID- 24941357
TI  - Risk factors for the development of PTSD and depression among child and
      adolescent victims following a 7.4 magnitude earthquake.
AB  - Objective. PTSD and major depression occur frequently following traumatic
      exposure, both as separate disorders and concurrently. Although much of Turkey is
      under threat of severe earthquakes, risk factors for developing psychiatric
      disorders among Turkish children have not yet been studied. The aim of the study
      was to examine risk factors for PTSD and depression develpoment in children.
      Method. A total of 160 survivors (102 girls and 58 boys) severely impacted by
      Turkey's 7.4-magnitude quake participated in a psychiatric interview 6-20 weeks
      after the disaster. The mean age was 14.43. Logistic regression was used to test
      effects of pre-disaster, disaster-related and post-disaster factors on diagnoses,
      yielding odds ratios (OR). Results. CAPS indicated that 96 (60%) had PTSD, and
      psychiatric interview found 49 (31%) with depression. Children diagnosed with
      PTSD were more likely to have witnessed death (OR=2.47) and experienced an
      extreme parental reaction (OR=3.45). Children with depression were more likely to
      be male (OR=4.48), have a higher trait anxiety score (OR=1.12 for every
      additional point), sustain injury (OR=4.29), and have lost a family member in the
      quake (OR=10.96). Focusing on the 96 children with PTSD, those with comorbid
      depression were more likely male, have a higher trait anxiety score, and have
      lost of family member. Conclusions. Mental health professionals should offer
      support to children witnessing death or losing a family member in a disaster. The
      ability of the family to remain calm and reassuring also may be a key factor in
      preventing PTSD. 

PMID- 24941358
TI  - Incidence and predictors of depression after stroke (DAS).
AB  - Objective. Depression after stroke (DAS) poses a treble burden to patients,
      families and health care system. The purpose of this paper is to estimate the
      incidence of depression among first-ever ischemic stroke patients and identify
      the predictors of DAS. Methods. A longitudinal study design was undertaken. Of
      836 patients admitted to the stroke unit of two regional hospitals in Hong Kong
      during the period 1 June 2004 to 31 May 2005, 295 patients fulfilled the
      inclusion and exclusion criteria. A total of 260 patients had given their
      consents and were interviewed at 1 month after stroke onset. Results. Nearly one
      quarter of the first ischemic stroke patients, who were known to be free of
      personal and family history of psychiatric illnesses, were found to satisfy the
      criteria of depression using Diagnostic and Statistical Manual IV (24%, 48 out of
      200 participants; 95% CI: 18.6%, 30.4%). This result was close to that assessed
      by the Geriatric Depression Scale (GDS) - 15 items. The psycho-emotional factor
      and level of dependency were found to be most significant predictors for DAS
      onset. Conclusion. The high incidence of DAS and low rate of accessibility to
      treatment indicate timely action to be undertaken. 

PMID- 24941359
TI  - Experience with risperidone long-acting injection: results of a naturalistic
      observation study.
AB  - Typical antipsychotics are effective in the management of schizophrenia, but are
      associated with troublesome adverse effects which may lead to treatment
      discontinuation and relapse. Long-acting depot formulations of these drugs
      improve patient compliance, but do not reduce the incidence of adverse effects.
      There is evidence to suggest that newer atypical antipsychotic drugs have a
      reduced propensity to induce movement disorders and are associated with a modest
      reduction in relapse rates. The introduction of risperidone long-acting injection
      (RLAI) provided clinicians with the first long-acting formulation of an atypical
      antipsychotic. Objective. The aim of this study was to investigate the outcomes
      of patients from an acute mental health trust who received RLAI during the 18
      month period following its licensing in the UK in order to examine measures of
      clinical effectiveness, and reasons for treatment discontinuation. Methods. Data
      were collected retrospectively from medical notes. Results. Fifty-nine patients
      were included in the study, and at the time of data collection 32 (54%) had
      discontinued treatment. The most common reason for discontinuation was lack of
      effectiveness, although all of the patients who discontinued due to lack of
      response were treatment resistant. RLAI appeared to be well tolerated, with only
      12% of patients discontinuing due to adverse effects. Thirty-eight percent of the
      patients treated with RLAI showed a good response as measured by discharge from
      inpatient setting, and of the 22 outpatients at time of data collection, five had
      one re-hospitalisation during the study period. Conclusion. This study concludes
      that RLAI appears to be well tolerated, and shows some effectiveness in the
      treatment of schizophrenia, but may not be effective for patients who are
      treatment resistant. 

PMID- 24941360
TI  - How should we inform patients about antidepressants? A study comparing verbal and
      written information.
AB  - Objective. To compare the efficacy of verbal, written and, combined verbal and
      written information about selective serotonin reuptake inhibitors in patients
      with depression. Method. Patients with a diagnosis of major depression who were
      prescribed selective serotonin reuptake inhibitors (n=104) were randomly
      allocated to verbal (n=34, 18F 16M), written (n=38, 19F 19 M) and verbal and
      written information (n=32, 18F 14M) groups, the content of the verbal and written
      information being exactly the same. Beck depression inventory was used to
      evaluate the depressive symptoms. Patients were called back after 10-14 days and
      their retention of the knowledge was measured. Results. The total retention
      scores of the verbal group, written group and the combined written and verbal
      group were 12.85+/-2.19, 7.39+/-2.85, and 13.19+/-2.12, respectively. The total
      scores of the verbal and the combined verbal and written information groups were
      significantly higher than those of the written group. The information scores had
      a significant positive correlation with education level. Conclusion. The
      retention of verbal information given to patients with low levels of depression
      concerning the effects and side effects of serotonin reuptake inhibitors is
      higher than written information. Further studies with more severely depressed
      patients, comparing the basal information level and the information level after
      the intervention and the effect of information on compliance are needed. 

PMID- 24941361
TI  - Obsessive-compulsive disorder in dermatology outpatients.
AB  - Introduction. Epidemiological findings have suggested that a large number of
      obsessional patients refer initially to dermatologists for their problems and
      their obsessions go undiagnosed. The goal of the present study is to investigate
      the frequency of OCD in a group of dermatology outpatients. Method. A total of
      144 outpatients of a dermatology clinic in a general hospital who agreed to
      participate in the study were selected. The patients were screened for DSM-IV OCD
      using item H of the Mini-International Neuropsychiatric Interview. Those who were
      OCD-positives on the interview were then screened and rated for severity on the
      Yale-Brown Obsessive-Compulsive Scale (YBOCS). Results. A total of 20 patients
      (14%) qualified for a diagnosis of OCD. Somatic obsessions and washing
      compulsions were the most reported symptoms. The majority of OCD-positive
      patients suffered from acne. Conclusion. The frequency of OCD in the dermatology
      population may be 4-5 times higher than in the general population. Identification
      and referral for psychiatric consultation may aid in better management of both
      disorders. 

PMID- 24941362
TI  - The "Seroquel" Outcomes Study (SOS): Efficacy and tolerability of quetiapine in a
      long-term, naturalistic study of patients with schizophrenia.
AB  - Objective. The "Seroquel" Outcomes Study (SOS) aimed to assess the efficacy and
      tolerability of quetiapine in patients with schizophrenia in the clinical
      practice setting. Methods. A 6-month, non-comparative, open-label study in adults
      with schizophrenia in a standard care setting in Spain. Outpatients received
      flexibly dosed quetiapine. Efficacy was evaluated using the Brief Psychiatry
      Rating Scale (BPRS) and the Clinical Global Impression (CGI) scale. BPRS response
      was defined as>=30% decrease from baseline. Tolerability was assessed using the
      Simpson-Angus Scale (SAS) and a modified Udvalg for Kliniske Undersogelser (UKU)
      side-effects scale. Results. A total of 2029 patients enrolled. Significant
      changes from baseline to Month 6 were recorded for BPRS total and subscale scores
      (P<0.001). Compared with doses of>=600 mg/day, doses of<400 mg/day were a strong
      predictor of a lower response rate (OR 0.62; 95% CI: 0.48, 0.82) and higher
      withdrawal rate (OR 3.3; 95% CI: 2.5, 4.4). Mean change in weight was minimal
      (+0.4 kg). Somnolence (26.7%), asthenia (12.5%), and constipation (9.8%) were the
      most common adverse events. Conclusion. Quetiapine was found to improve symptoms
      of schizophrenia, as indicated by a significant decrease in BPRS scores, and was
      well tolerated by patients in clinical practice. 

PMID- 24941363
TI  - Treatment of depression with selective serotonin inhibitors: the role of
      fluvoxamine.
AB  - The advent of the selective serotonin reuptake inhibitors (SSRIs) is generally
      considered to have improved the treatment of depression. Head-to-head trials
      comparing SSRIs to each other have shown little difference in efficacy among
      agents. The main differences between the SSRIs relate to safety and tolerability
      profiles, reflecting the fact that the SSRIs possess significant and variable
      secondary pharmacological properties. This heterogeneity contributes to
      clinically relevant differences that clinicians are increasingly using to select
      antidepressant treatment more closely appropriate to specific patient populations
      and circumstances. This review assesses the place of fluvoxamine amongst the
      SSRIs in the context of current issues and concerns with drug therapy.
      Fluvoxamine has a proven efficacy and safety profile in treating elderly patients
      with depression. The beneficial effects of fluvoxamine in obsessive-compulsive
      disorder (OCD) are also well documented. On the other hand, its sigma1-receptor
      binding profile may account for the observed high level of efficacy in psychotic
      depression and may explain the benefit of fluvoxamine in treating depression
      comorbid with anxiety/stress. There is no definitive evidence that suicide risk
      is higher with SSRIs than with other antidepressants or nonpharmacological
      treatments and postmarketing surveillance indicates that fluvoxamine is not
      associated with a higher level of suicidality. 

PMID- 24941364
TI  - Gilbert's syndrome in a patient with predominantly negative symptoms of
      schizophrenia.
AB  - Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome) is a common
      genetic enzyme deficiency found in 3-10% of the general population. It occurs
      with greater frequency in patients with schizophrenia. We report the case of a
      young man with mainly negative symptoms of schizophrenia in whom there has been
      little improvement in mental state with prolonged treatment despite an
      improvement in total bilirubin, contrary to other published cases. We examine the
      literature related to Gilbert's syndrome and symptom severity and we discuss the
      research into the pathophysiology of schizophrenia in Gilbert's syndrome and
      negative symptom schizophrenia. 

PMID- 24941365
TI  - Mirtazapine treatment and sexual functions: Results of a Hungarian, multicentre,
      prospective study in depressed out-patients.
AB  - Since many antidepressants can cause sexual dysfunction, the aim of this study
      was to follow-up sexual functions during mirtazapine (RemeronSolTab(r))
      treatment. One hundred and two (44 male and 58 female) outpatients with major
      depression were recruited to this prospective, observational, non-interventional
      study. The screening was followed by three visits, during which the 17-HAMD, CGI
      and 9-BDI scales were used. The change of sexual life was monitored by a self
      completing questionnaire, based on the modified Psychotropic-Related Sexual
      Dysfunction Questionnaire. During the treatment both the depression rating scales
      and the CGI have shown a significant improvement and significant amelioration of
      previous sexual problems was found; patients were evaluating their sexual life
      better and better. Our results indicated that mirtazapine is an effective tool
      for depressed patients who suffer from sexual dysfunction. 

PMID- 24941366
TI  - Antipsychotic drugs as a risk factor for venous thromboembolism.
AB  - Objective. We assessed whether antipsychotic drugs represent a risk factor for
      venous thromboembolism by comparing the prevalence of antipsychotic drugs use in
      a population of patients with venous thromboembolism versus a group of
      individuals treated for hypertension. Methods. We identified 266 patients (141
      women) diagnosed as having venous thromboembolism at the average age of 43.1+/-11
      years who had been hospitalized in the University Hospital in Hradec Kralove from
      1 January 1996 to 31 December 2004. Two hundred and seventy-four patients (140
      women) with arterial hypertension, with an average age of 48.3+/-8.8 years,
      represented the control population. Results. Use of antipsychotic drugs was
      moderately more frequent in the group of patients with venous thromboembolism as
      compared with the control group subjects (4.89 vs. 1.82%; odds ratio 2.76; 95%
      confidence interval=1.01-7.55). Discussion. We discuss the possible mechanisms of
      venous thromboembolism induced by antipsychotic agents - hypoactivity, blood
      status, obesity, abnormal coagulation, autoimmune mechanisms, and
      hyperhomocysteinemia. Conclusion. Our results indicate the possibility of an
      increased risk for venous thromboembolism in patients using antipsychotic drugs.
      It is necessary to seriously consider this possible adverse effect owing to its
      potentially fatal consequences. 

PMID- 24941367
TI  - Molecular heterosis in metamphetamine abusers.
AB  - Objective. The aim of our study was to assess whether the catechol-O
      methyltransferase (COMT) genetic background of patients dependent on
      metamphetamine is related to their non-abstinence in a 1-year follow-up. Methods.
      We examined COMT gene Val158Met polymorphism and 1-year abstinence in a group of
      31 (women N=8) Czech Caucasian metamphetamine abusers (average age, 23.8+/
      4.0years). Results. Non-abstinence was significantly (P=0.046, Fisher's exact
      test) associated with the heterozygous Val/Met genotype. Conclusion. The case
      where subjects heterozygous for a specific genetic polymorphism show a
      significantly greater or lesser effect for a phenotypic trait than subjects
      homozygous for either allele is described as molecular heterosis in the
      literature. We discuss several explanations and recommendations for further
      research. 

PMID- 24941369
TI  - A repA-based ELISA for discriminating cattle vaccinated with Brucella suis 2 from
      those naturally infected with Brucella abortus and Brucella melitensis.
AB  - The commonest ways of diagnosing brucellosis in animals include the Rose-Bengal
      plate agglutination test, the buffered plate agglutination test (BPA), the slide
      agglutination test, the complement fixation test, and the indirect enzyme linked
      immunosorbent assay (I-ELISA). However, these methods cannot discriminate the
      Brucella vaccine strain (Brucella suis strain 2; B. suis S2) from naturally
      acquired virulent strains. Of the six common Brucella species, Brucella
      melitensis, Brucella abortus, and B. suis are the commonest species occurring in
      China. To develop an ELISA assay that can differentiate between cows inoculated
      with B. suis S2 and naturally infected with B. abortus and B. melitensis, genomic
      sequences from six Brucella spp. (B. melitensis, B. abortus, B. suis, Brucella
      canis, Brucella neotomae and Brucella ovis) were compared using Basic Local
      Alignment Search Tool software. One particular gene, the repA-related gene, was
      found to be a marker that can differentiate B. suis from B. abortus and B.
      melitensis. The repA-related gene of B. suis was PCR amplified and subcloned into
      the pET-32a vector. Expressed repA-related protein was purified and used as an
      antigen. The repA-based ELISA was optimized and used as specific tests. In the
      present study, serum from animals inoculated with the B. suis S2 vaccine strain
      had positive repA-based ELISA results. In contrast, the test-positive reference
      sera against B. abortus and B. melitensis had negative repA-based ELISA results.
      The concordance rate between B. abortus antibody-negative (based on the repA
      based ELISA) and the Brucella gene-positive (based on the 'Bruce ladder'
      multiplex PCR) was 100%. Therefore, the findings suggest that the repA-based
      ELISA is a useful tool for differentiating cows vaccinated with the B. suis S2
      and naturally infected with B. abortus and B. melitensis.

PMID- 24941371
TI  - NK cell phenotypic and functional heterogeneities and molecular mechanisms of
      cytotoxicity.
AB  - Natural killer (NK) cells were discovered four decades ago, independently, by the
      Kiessling and Herberman groups. Since then, significant advances have accrued
      regarding the functional and molecular properties of NK cells as well as their
      clinical relevance. The important feature of NK cells is their inability to kill
      normal cells, while they are highly cytotoxic for infected or transformed cells.
      This discrimination has been largely resolved by the discovery of both activating
      and inhibitory receptors on NK cells and corresponding ligands on target cells.
      This review focuses briefly on several issues related to NK cells: (1) the
      phenotypic properties of NK cells, (2) the heterogeneity of NK cell activities,
      (3) the determination of three major NK subsets (Free, Binder, and Killer), (4)
      the maturation and activation of NK subsets, (5) the response of NK cells to
      various cytokines, (6) the target-induced inactivation and cell death of NK
      cells, (7) the multiple mechanisms of cell-mediated cytotoxicity, (8) the
      characterization of NK cytotoxic factors (NKCF), and (9) the role of membrane
      fluidity in cytotoxicity. These subjects are described chronologically beginning
      shortly after the discovery of NK cells as a result of Ron Herberman's
      leadership, and I am gratefully indebted to him. 

PMID- 24941372
TI  - Measurements of natural killer (NK) cells.
AB  - In this article, we describe currently available methods for measuring NK cell
      functions: cytotoxicity and cytokine expression using flow cytometry-based assays
      and cytokine production using the Luminex-based technology. Quality control
      measures necessary for assay accuracy and reliability are also addressed. 

PMID- 24941370
TI  - Natural killer activity: early days, advances, and seminal observations.
AB  - This manuscript describes the early history of NK cell discovery, with emphasis
      on the events in the first decade of NK cell studies, 1972-1982. The authors
      highlight some of the earliest and most important observations that would later
      prove to be milestones in the study of NK cells and their activity. 

PMID- 24941374
TI  - Dendritic cell editing by natural killer cells.
AB  - Activated, mature, dendritic cells (DCs) are the main antigen-presenting cells
      for initiating adaptive immune responses, whereas immature DCs have been
      implicated in tolerance and induction of regulatory T cells. It is now well
      established that NK cells are able to discriminate between mature and immature
      DCs by killing the latter because of their low amount of surface human leukocyte
      antigen (HLA) class I molecules. Thus, NK cells are thought to play an important
      regulatory role by selectively editing DCs during the course of immune responses.
      NK-mediated killing of immature (but not mature) DCs results in selection of
      immunogenic DCs during the initiation of anti-cancer immune responses. In
      addition to the removal of inappropriate DCs, NK cells can also shape adaptive
      immune responses by promoting DC maturation and influencing the polarization of
      primary T-cell responses. DC-NK cell interactions should be carefully considered
      in DC-based cancer vaccine strategies. Optimal NK cell activation should be
      sought to enhance the magnitude and the quality of both innate and adaptive
      immune responses against tumors. 

PMID- 24941373
TI  - Positive and negative regulation by NK cells in cancer.
AB  - Our understanding of NK biology has expanded immensely since the initial
      discovery of natural killer cells in 1975. New studies have uncovered various
      levels of immune regulation both on and by unique subsets of NK cells, which go
      well beyond simple receptor-ligand interactions between NK cells and target
      cancer cells. Distinct suppressor and effector populations of NK cells have been
      delineated in both viral and tumor models. Interactions between NK cells and
      dendritic cells, T cells, and B cells also dramatically alter the overall immune
      response to cancer. To exploit the diverse functional abilities of NK cell
      subsets for cancer immunotherapies, it is important to understand NK cell biology
      and NK regulator mechanisms. 

PMID- 24941375
TI  - The pathophysiological role of chemokines in the regulation of NK cell tissue
      homing.
AB  - Natural killer (NK) cells are an essential component of innate immunity that can
      rapidly detect and respond to malignant or infected cells. Chemokines play
      important roles in directing immune responses by controlling tissue homing,
      retention, and activation of immune cells. Although some chemokines can promote
      tumor growth and metastasis, others are responsible for extensive infiltration of
      lymphocytes, thus resulting in a protective anti-tumor immune response. Here, we
      summarize discoveries that have revealed the role of specific chemokines in
      regulating the function of NK cells during inflammation, infection, and
      malignancies. 

PMID- 24941376
TI  - NK cells in the tumor microenvironment.
AB  - The presence of natural killer (NK) cells in the tumor microenvironment
      correlates with outcome in a variety of cancers. However, the role of
      intratumoral NK cells is unclear. Preclinical studies have shown that, while NK
      cells efficiently kill circulating tumor cells of almost any origin, they seem to
      have very little effect against the same type of tumor cells when these have
      extravasated. The ability to kill extravasated tumor cells is, however, is
      dependent of the level of activation of the NK cells, as more recent published
      and unpublished studies, discussed below, have demonstrated that interleukin-2
      activated NK cells are able to attack well-established solid tumors. 

PMID- 24941378
TI  - Clinical grade purification and expansion of natural killer cells.
AB  - Natural killer (NK) cells have been shown to have important functions in anti
      tumor responses and therefore have been used as adoptive immunotherapy for
      cancer. Here, we review the current methods of ex vivo activation, enrichment,
      expansion, and shipment of clinical NK cell products. 

PMID- 24941377
TI  - NK cells and virus-related cancers.
AB  - Natural killer (NK) cells become activated during viral infections and can play
      roles in such infections by attacking virus-infected cells or by regulating
      adaptive immune responses. Experimental models suggest that NK cells may also
      have the capacity to restrain virus-induced cancers. Here, we discuss the seven
      viruses linked to human cancers and the evidence of NK cell involvement in these
      systems. 

PMID- 24941383
TI  - What is your diagnosis? Infiltrative lipomas.

PMID- 24941379
TI  - NK cells in therapy of cancer.
AB  - Natural killer (NK) cells recognize targets stressed by malignant transformation
      or infection and can be long-lived. They become educated by interacting with
      major histocompatibility antigen (MHC) class I molecules to gain function to kill
      targets and produce cytokines. In the clinic, haploidentical NK cells can be
      adoptively transferred to treat cancer. Persistence and in vivo expansion of NK
      cells depends on lymphodepleting chemotherapy to make space and induce release of
      endogenous IL-15. In vivo expansion is also enhanced by cytokine administration
      but IL-2 has the down side of stimulating CD25hi regulatory T cells (Tregs).
      Other limitations to NK-cell therapy include poor in vivo survival and lack of
      specificity. Bispecific or trispecific killer engagers that target CD16 on NK
      cells to enhance recognition of tumor antigens, and desintegrin and
      metalloproteinase 17 (ADAM17) inhibition that prevents CD16 shedding after NK
      cell activation should promote enhanced killing of cancer with specificity. These
      are exciting times; more than 35 years after NK cells were initially described,
      we are exploiting their capacity for clinical therapy. 

PMID- 24941384
TI  - What is your diagnosis? Myocardial calcification.

PMID- 24941387
TI  - ECG of the Month. Escape-capture bigeminy in a cat.

PMID- 24941386
TI  - What is your neurologic diagnosis? Fibrocartilaginous embolism in a cat.

PMID- 24941388
TI  - Pathology in practice. Malignant mesothelioma in a dog.

PMID- 24941389
TI  - A review of bird welfare during controlled atmosphere and electrical water-bath
      stunning.

PMID- 24941390
TI  - Success rates of various techniques for reduction of twin pregnancy in mares.

PMID- 24941391
TI  - Performance of a commercially available in-clinic ELISA for detection of
      antibodies against Anaplasma phagocytophilum, Anaplasma platys, Borrelia
      burgdorferi, Ehrlichia canis, and Ehrlichia ewingii and Dirofilaria immitis
      antigen in dogs.
AB  - OBJECTIVE: To evaluate the performance of an in-clinic ELISA designed for
      detection of heartworm antigen and antibodies against 5 tick-borne pathogens.
      DESIGN: Validation study. SAMPLE: 1,601 serum or matched serum, plasma, and blood
      samples from dogs. PROCEDURES: Samples were tested for Dirofilaria immitis
      (heartworm) antigen and antibodies against Anaplasma phagocytophilum, Anaplasma
      platys, Borrelia burgdorferi, Ehrlichia canis, and Ehrlichia ewingii by means of
      an in-clinic ELISA. Evaluation of assay sensitivity and specificity, agreement of
      results among sample types, and cross-reactivity of E canis antigens in the assay
      with anti-Ehrlichia chaffeensis antibodies in stored samples from experimentally
      infected dogs were performed at a reference laboratory. Field tests of the in
      clinic ELISA were performed at 6 veterinary facilities. Results were compared
      with confirmatory test results. RESULTS: Sensitivity and specificity of the in
      clinic ELISA were > 89% for detection of antibodies against A phagocytophilum
      (93.2% and 99.2%, respectively), A platys (89.2% and 99.2%, respectively), B
      burgdorferi (96.7% and 98.8%, respectively), E canis (97.8% and 92.3%,
      respectively), and E ewingii (96.5% and 93.9%, respectively). Sensitivity of the
      assay for detection of D immitis was 98.9%, with 99.3% specificity. The in-clinic
      ELISA identified exposure to > 1 vector-borne pathogen in 354 of 1,195 samples.
      Cross-reactivity of E canis antigens with anti-E chaffeensis antibodies was
      confirmed. Results of field evaluations confirmed that the in-clinic ELISA could
      be reliably used under typical clinical conditions to identify dogs exposed to
      the pathogens of interest. CONCLUSIONS AND CLINICAL RELEVANCE: The in-clinic
      ELISA provided a comprehensive in-house serologic screening test for all vector
      borne pathogens evaluated.

PMID- 24941392
TI  - Performance of two portable meters and a benchtop analyzer for blood glucose
      concentration measurement in rabbits.
AB  - OBJECTIVE: To evaluate performance of a human portable blood glucose meter
      (PBGM), a veterinary PBGM, and a veterinary benchtop analyzer for measuring blood
      glucose concentration in rabbits and to evaluate the effect of sample
      characteristics on their performance. DESIGN: Observational prospective cross
      sectional study. SAMPLE: Blood samples from 89 pet rabbits. PROCEDURES: Blood
      glucose concentration was measured with a human PBGM (n = 89 rabbits), a
      veterinary PBGM (89), and a benchtop analyzer (32) and compared with results
      obtained with plasma in a laboratory analyzer (hexokinase method). RESULTS: The
      human PBGM underestimated blood glucose concentration, had decreased accuracy at
      high Hcts, and had the lowest total error observed (11.4%). The veterinary PBGM
      overestimated blood glucose concentration, had decreased accuracy at low Hcts and
      at high blood glucose concentrations, and had the highest total error (15.5% and
      29.8% for canine and feline settings, respectively). The benchtop analyzer had
      good accuracy and was not influenced by Hct or glucose concentrations. Clinical
      errors would have occurred in 0% of cases with the human PBGM and with the
      benchtop analyzer and in 9% (canine setting) to 6.7% (feline setting) of cases
      with the veterinary PBGM. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that use of the human PBGM evaluated in this study would be acceptable for point
      of-care testing of blood glucose concentration in rabbits when benchtop analyzers
      are not available. The use of the veterinary PBGM evaluated in this study may
      alter both treatment and diagnostic decisions because of the overestimation of
      glucose concentrations in some rabbits.

PMID- 24941393
TI  - Total dietary fiber composition of diets used for management of obesity and
      diabetes mellitus in cats.
AB  - OBJECTIVE: To determine total dietary fiber (TDF) composition of feline diets
      used for management of obesity and diabetes mellitus. DESIGN: Cross-sectional
      survey. SAMPLE: Dry veterinary (n = 10), canned veterinary (12), and canned over
      the-counter (3) feline diets. PROCEDURES: Percentage of TDF as insoluble dietary
      fiber (IDF), high-molecular-weight soluble dietary fiber (HMWSDF), and low
      molecular-weight soluble dietary fiber (LMWSDF) was determined. RESULTS: Median
      measured TDF concentration was greater than reported maximum crude fiber content
      in dry and canned diets. Median TDF (dry-matter) concentration in dry and canned
      diets was 12.2% (range, 8.11% to 27.16%) and 13.8% (range, 4.7% to 27.9%),
      respectively. Dry and canned diets, and diets with and without a source of
      oligosaccharides in the ingredient list, were not different in energy density or
      concentrations of TDF, IDF, HMWSDF, or LMWSDF. Similarly, loaf-type (n = 11) and
      gravy-type (4) canned diets differed only in LMWSDF concentration. Disparities in
      TDF concentrations among products existed despite a lack of differences among
      groups. Limited differences in TDF concentration and dietary fiber composition
      were detected when diets were compared on the basis of carbohydrate
      concentration. Diets labeled for management of obesity were higher in TDF
      concentration and lower in energy density than diets for management of diabetes
      mellitus. CONCLUSIONS AND CLINICAL RELEVANCE: Diets provided a range of TDF
      concentrations with variable concentrations of IDF, HMWSDF, and LMWSDF. Crude
      fiber concentration was not a reliable indicator of TDF concentration or dietary
      fiber composition. Because carbohydrate content is calculated as a difference,
      results suggested that use of crude fiber content would cause overestimation of
      both carbohydrate and energy content of diets.

PMID- 24941394
TI  - Prevalence and clinical outcome of subclinical bacteriuria in female dogs.
AB  - OBJECTIVE: To determine the prevalence of subclinical bacteriuria and its natural
      clinical course over a 3-month period in healthy female dogs. DESIGN:
      Observational, prospective, cross-sectional study. ANIMALS: 101 healthy client
      owned female dogs. PROCEDURES: In all dogs, screening clinicopathologic tests and
      bacteriologic culture of urine were performed. In culture-positive dogs,
      subclinical bacteriuria was confirmed by 2 positive culture results within 2
      weeks and dogs were reevaluated at 3 months. RESULTS: The prevalence of
      subclinical bacteriuria in healthy female dogs was 9 of 101 (8.9%). Three-month
      follow-up data were available for 8 of 9 dogs with subclinical bacteriuria. Four
      dogs had persistent bacteriuria, and 4 had transient bacteriuria. No dogs with
      subclinical bacteriuria developed clinical signs during the 3-month observation
      period. Subclinical bacteriuria was diagnosed in 6 of 51 (12%) young and middle
      aged dogs and 3 of 50 (6.0%) senior and geriatric dogs. No significant difference
      was found in the prevalence of subclinical bacteriuria with age. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that subclinical bacteriuria is a
      nonprogressive condition in healthy female dogs and can be persistent or
      transient. No significant difference in the prevalence of subclinical bacteriuria
      in young and middle-aged dogs versus senior and geriatric dogs was detected. No
      dogs with subclinical bacteriuria developed clinical signs requiring
      antimicrobial treatment during the 3-month observation period. Healthy female
      dogs with subclinical bacteriuria may be a population of dogs in which
      antimicrobial treatment is unnecessary.

PMID- 24941395
TI  - Ischemic stroke in Greyhounds: 21 cases (2007-2013).
AB  - OBJECTIVE: To determine the prevalence of ischemic stroke in Greyhounds and
      determine whether affected dogs had coagulation abnormalities and hypertension.
      DESIGN: Multi-institutional, retrospective study. ANIMALS: 21 dogs. PROCEDURES:
      Medical records (including diagnostic testing results) and MRI images of the
      brain were reviewed for Greyhounds with ischemic stroke that had been evaluated
      at 4 institutions. The proportion of Greyhounds with ischemic stroke was compared
      with the proportion of non-Greyhound dogs with ischemic stroke. Demographic
      information for dogs evaluated at each institution was obtained to determine the
      proportion of Greyhounds in the hospital populations. RESULTS: 21 Greyhounds with
      ischemic stroke were identified. Abnormalities in coagulation were not identified
      in the 14 Greyhounds that underwent such testing. Systemic hypertension was
      identified in 6 of 14 Greyhounds that underwent such testing. No other
      abnormalities were identified by means of other routine diagnostic tests for
      Greyhounds. For all institutions combined, the prevalence of ischemic stroke in
      Greyhounds was 0.66% (21/3,161 Greyhounds). Greyhounds were significantly more
      likely to be evaluated because of ischemic stroke, compared with all other dog
      breeds combined (OR, 6.6; 95% confidence interval, 4.2 to 10.2). CONCLUSIONS AND
      CLINICAL RELEVANCE: Results of this study suggested that Greyhounds were
      predisposed to ischemic stroke, compared with all other breeds combined.
      Coagulation abnormalities did not seem to contribute to ischemic stroke.
      Hypertension may have contributed to the development of ischemic stroke.
      Greyhounds with ischemic stroke should undergo measurement of systolic arterial
      blood pressure. Antihypertensive treatments may be warranted for such dogs.

PMID- 24941396
TI  - Cardiac troponin I concentrations in horses with colic.
AB  - OBJECTIVE: To determine prevalence of myocardial injury in horses with colic on
      the basis of high concentrations of cardiac troponin I (cTnI), frequency of
      cardiac arrhythmias within the first 24 to 48 hours after hospital admission or
      surgery because of colic, and associations between high cTnI concentrations and
      cardiac arrhythmias, clinical course, and outcome (survival to discharge from
      hospital vs nonsurvival [death or euthanasia]). DESIGN: Prospective observational
      study. ANIMALS: 111 horses with colic. PROCEDURES: Blood was drawn at admission
      and 12 and 24 hours after admission if horses were treated medically or 12 and 24
      hours after surgery if treated surgically. A 24-hour ambulatory ECG was recorded
      beginning the morning after admission in medically treated cases or after surgery
      and evaluated for arrhythmias. Clinical and clinicopathologic data and outcome
      were obtained. Associations between cTnI concentrations and other variables were
      determined. RESULTS: An abnormal cTnI concentration (>= 0.10 ng/mL) at admission
      was significantly associated with the occurrence of ventricular arrhythmias,
      outcome, and surgical treatment. CONCLUSIONS AND CLINICAL RELEVANCE: The data
      suggested that horses with colic and high cTnI concentrations at admission were
      more likely to have ventricular arrhythmias and have a less favorable prognosis
      for recovery. High cTnI concentrations in horses with colic were suggestive of
      myocardial damage.

PMID- 24941397
TI  - Use of digital abdominal radiography for the diagnosis of enterolithiasis in
      equids: 238 cases (2008-2011).
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of direct digital
      abdominal radiography for the diagnosis of enterolithiasis in equids and to
      assess the effect of the number and anatomic location of enteroliths and gas
      distention of the gastrointestinal tract on diagnostic sensitivity of the
      technique. DESIGN: Retrospective case series. SAMPLE POPULATION: 238 horses and
      ponies >= 1 year old that underwent digital abdominal radiography with subsequent
      exploratory celiotomy or postmortem examination. PROCEDURES: For each case, 3
      reviewers independently evaluated radiographic views. Radiographic images were
      evaluated for presence or absence and location of enteroliths and the degree of
      gas distention. Signalment, definitive diagnosis based on exploratory celiotomy
      or postmortem examination findings, and number and anatomic location of
      enteroliths were obtained from the medical records. RESULTS: 70 of the 238
      (29.4%) equids had confirmed enterolithiasis. With regard to diagnosis of
      enterolithiasis via digital radiography, overall sensitivity and specificity for
      the 3 reviewers were 84% and 96%, respectively. Sensitivity was lower for small
      colon enteroliths (61.5%) than for large colon enteroliths (88.9%) and was
      negatively affected by gas distention of the gastrointestinal tract. Sensitivity
      was not affected by the number of enteroliths. CONCLUSIONS AND CLINICAL
      RELEVANCE: Sensitivity and specificity of digital radiography for the diagnosis
      of large colon enterolithiasis in equids was high. Sensitivity of digital
      radiography for detection of small colon enteroliths was lower than that for
      large colon enteroliths, but was higher than that typically associated with
      computed radiography. In geographic regions in which enterolithiasis in equids is
      endemic, digital abdominal radiography could be used as a diagnostic test for
      equids with colic.

PMID- 24941398
TI  - Levothyroxine or minimally invasive therapies for benign thyroid nodules.
AB  - BACKGROUND: Thyroid nodules (TN) are common in the adult population. Some
      physicians use suppressive levothyroxine (LT4) therapy to achieve a reduction in
      the number and volume of TN. In addition, minimally invasive treatments, such as
      percutaneous ethanol injection (PEI) sclerotherapy, laser photocoagulation (LP),
      and microwave (MW), radiofrequency (RF) and high-intensity focused ultrasound
      (HIFU) ablation, have been proposed, especially for pressure symptoms and
      cosmetic complaints, as an alternative to surgery. However, the risk to benefit
      ratio of all treatments for benign TN is currently unknown. OBJECTIVES: To assess
      the effects of LT4 or minimally invasive therapies (PEI, LP, and RF/HIFU/MW
      ablation) on benign TN. SEARCH METHODS: We identified studies from computerised
      searches of The Cochrane Library, MEDLINE, EMBASE and LILACS (all performed up to
      April 2014). We also searched trial registers, examined reference lists of
      included randomised controlled trials (RCTs) and systematic reviews, and
      contacted study authors. SELECTION CRITERIA: We included studies if they were
      RCTs of LT4, PEI, LP, RF, HIFU or MW therapy in participants with an established
      diagnosis of benign TN. We excluded trials investigating the prevention of
      recurrence of thyroid disease after surgery, irradiation or treatment with
      radioiodine. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data, assessed studies for risk of bias and evaluated overall study
      quality utilising the GRADE instrument. We assessed the statistical heterogeneity
      of included studies by visually inspecting forest plots and quantifying the
      diversity using the I2 statistic. We synthesised data using random-effects model
      meta-analysis or descriptive analysis, as appropriate. MAIN RESULTS: Thirty-one
      studies randomised 2952 outpatients to investigate the effects of different
      therapies on benign TN. Studies on LT4, PEI, LP and RF ablation therapy
      randomised 2083, 607, 192 and 70 participants, respectively. We found no RCTs of
      HIFU or MW ablation therapy in benign TN. The duration of treatment varied
      according to the applied therapies: up to five years for LT4 and one to three PEI
      ablations, one to three LP sessions and one or two RF sessions. Median follow-up
      was 12 months for LT4 and six months for minimally invasive therapies. Evidence
      was of low-to-moderate quality, and risk of performance and detection bias for
      subjective outcomes was high in most trials.No study evaluated all-cause
      mortality or health-related quality of life. Only one LT4 study provided some
      data on the development of thyroid cancer, reporting no abnormal cytological
      findings. One LP study provided limited information on costs of treatment.LT4
      compared with no treatment or placebo was associated with a nodule volume
      reduction of 50% or more in 16% compared with 10% of participants after 6 to 24
      months of follow-up (risk ratio (RR) 1.57 (95% confidence interval (CI) 1.04 to
      2.38); P = 0.03; 958 participants; 10 studies; moderate-quality evidence).
      Pressure symptoms or cosmetic complaints were not investigated in LT4 studies.
      LT4 therapy was generally well tolerated: three studies provided quantitative
      data on signs and symptoms of hyperthyroidism, which were observed in 25% of LT4
      treated versus 7% of placebo-treated participants at 12 to 18 months of follow-up
      (269 participants; 3 trials; low-quality evidence).PEI compared with cyst
      aspiration only was associated with a nodule volume reduction of 50% or more in
      83% compared with 44% of participants after 1 to 24 months of follow-up (RR 1.83
      (95% CI 1.32 to 2.54); P = 0.0003; 105 participants; 3 studies; low-quality
      evidence). Improvements in neck compression symptoms after 6 to 12 months of
      follow-up were seen in 78% of participants receiving PEI versus 38% of those in
      comparator groups. No reliable summary effect estimate could be established, RR
      ranged from 1.0 to 3.06 in favour of PEI (370 participants; 3 trials; low-quality
      evidence). In all trials, participants experienced periprocedural cervical
      tenderness and light-to-moderate pain usually lasting from minutes to several
      hours. As a result of the PEI procedure, 26% of participants reported slight-to
      moderate pain compared with 12% of those receiving cyst aspiration only (RR 1.78
      (95% CI 0.62 to 5.12); P = 0.28; 104 participants; 3 studies; low-quality
      evidence).One study comparing LP with LT4 showed a nodule volume reduction of 50%
      or more in favour of LP after 12 months of follow-up in 33% of LP participants
      versus 0% of LT4 participants, respectively (62 participants; 1 trial; low
      quality evidence). A total of 82% of LP-treated versus 0% of untreated
      participants showed improvements in pressure symptoms after 6 to 12 months of
      follow-up (RR 26.65 (95% CI 5.47 to 129.72); P < 0.0001; 92 participants; 3
      trials; low-quality evidence). Around 20% of LP-treated participants reported
      light-to-moderate cervical pain lasting 48 hours or more (97 participants; 3
      trials; low-quality evidence).One trial with 40 participants, comparing RF with
      no treatment, resulted in a mean nodule volume reduction of 76% in the RF group
      compared with 0% of those in the no-treatment group at six months of follow-up
      (low-quality evidence). These RF-treated participants had fewer pressure symptoms
      and cosmetic complaints after 12 months of follow-up compared with untreated
      participants (a 2.8 decrease versus a 1.1 increase on a six-point scale,
      respectively, with higher values indicating more severe symptoms; low-quality
      evidence). All participants complained of pain and discomfort during RF, which
      disappeared when the energy was reduced or turned off (low-quality evidence).
      AUTHORS' CONCLUSIONS: No study evaluated all-cause mortality, health-related
      quality of life or provided systematic data on the development of thyroid cancer.
      Longest follow-up was five years and median follow-up was 12 months. Nodule
      volume reductions were achieved by PEI, LP and RF, and to a lesser extent, by
      LT4. However, the clinical relevance of this outcome measure is doubtful. PEI, LP
      and RF led to improvements in pressure symptoms and cosmetic complaints. Adverse
      events such as light-to-moderate periprocedural pain were seen after PEI, LP and
      RF. Future studies should focus on patient-important outcome measures, especially
      health-related quality of life, and compare minimally invasive procedures with
      surgery. RCTs with follow-up periods of several years and good-quality
      observational studies are needed to provide evidence on the development of
      thyroid cancer, all-cause mortality and long-term adverse events.

PMID- 24941399
TI  - Clickable Cgamma-azido(methylene/butylene) peptide nucleic acids and their
      clicked fluorescent derivatives: synthesis, DNA hybridization properties, and
      cell penetration studies.
AB  - Synthesis, characterization, and DNA complementation studies of clickable
      C(gamma)-substituted methylene (azm)/butylene (azb) azido PNAs show that these
      analogues enhance the stability of the derived PNA:DNA duplexes. The fluorescent
      PNA oligomers synthesized by their click reaction with propyne carboxyfluorescein
      are seen to accumulate around the nuclear membrane in 3T3 cells. 

PMID- 24941400
TI  - Case report: Pseudotumor associated with corrosion of a femoral component with a
      modular neck and a ceramic-on-polyethylene bearing.
AB  - Pseudotumor is a rare complication that can occur following hip arthroplasty.
      This complication may present with pain, swelling, and decreased function and may
      lead to bone and soft-tissue destruction. We report a case of pseudotumor
      formation resulting from corrosion of a modular neck in a hip replacement with a
      ceramic-on-polyethylene bearing. The patient underwent successful revision
      surgery using an extended trochanteric osteotomy, removal of the entire stem, and
      implantation of a new femoral stem and ceramic-polyethylene bearing without a
      modular neck. 

PMID- 24941401
TI  - Local tissue reaction and necrosis-induced femoral nerve palsy in a patient with
      a metal-on-metal total hip arthroplasty: a case report.
AB  - This case report describes a 54-year-old Hispanic male who developed femoral
      nerve palsy approximately 1 year after metal-on-metal total hip arthroplasty (MOM
      THA). Cobalt and chromium levels were 4.8 ppb and undetectable, respectively. MRI
      demonstrated a well-encapsulated pseudotumor that communicated with the anterior
      portion of the right hip, and EMG showed neuropraxic femoral nerve injury. As a
      result, the patient experienced motor and sensory loss in the femoral and
      proximal saphenous nerve distributions. Surgical revision to ceramic-on-poly THA
      with debridement and decompression of the pseudotumor improved the patient's
      neurological status. Similar acute local tissue reactions have been described but
      the serum levels of cobalt and chrome associated with these reactions have been
      variable. Wear particles and products produced from corrosion at the head taper
      junction from MOM THA can potentially lead to cellular dysfunction with
      subsequent pseudotumer formation, but these reactions and fluid collections have
      also been found. In this patient, serum cobalt levels were elevated, while serum
      chromium levels remained undetectable. The purpose of this case report is to
      describe one patient's response and to review the recent literature regarding
      potential complications of MOM THA. 

PMID- 24941403
TI  - Evaluation and management of metal hypersensitivity in total joint arthroplasty:
      a systematic review.
AB  - Metal hypersensitivity has been an identified problem in orthopedics for nearly
      half a century, but its implications remain unclear. Establishing which total
      joint arthroplasty (TJA) candidates may do poorly with conventional implants and
      which patients would benefit from revision to an allergen-free implant remains
      challenging. Our systematic search of the MEDLINE database identified 52 articles
      for inclusion in our review. Case reports revealed that half of patients
      presented with pain and swelling, while only one-third presented with cutaneous
      symptoms. All patients were symptomatic within the first post-operative year; 90%
      were symptomatic within 3 months. Reports of patch testing revealed that patients
      with TJAs were positive for metal sensitivity more often than patients without
      TJAs (OR 1.3). Those with poorly functioning arthroplasties and those who had
      already had revisions tested positive more often than those with well-functioning
      TJAs (OR 1.7) and those without TJAs (OR 3.1). Lymphocyte transformation testing
      (LTT) shows promise in diagnosing metal allergy, and components of bone cement
      are also being recognized as potential allergens. Further work is necessary to
      delineate which patients should be tested for metal allergy and which patients
      would benefit from allergen-free implants. 

PMID- 24941402
TI  - Histological characterization of periprosthetic tissue responses for metal-on
      metal hip replacement.
AB  - The histology of periprosthetic tissue from metal-on-metal (MOM) hip devices has
      been characterized using a variety of methods. The purpose of this study was to
      compare and evaluate the suitability of two previously developed aseptic
      lymphocyte-dominated vasculitis-associated lesions (ALVAL) scoring systems for
      periprosthetic hip tissue responses retrieved from MOM total hip replacement
      (THR) systems revised for loosening. Two ALVAL scoring systems (Campbell and
      Oxford) were used to perform histological analyses of soft tissues from 17 failed
      MOM THRs. The predominant reactions for this patient cohort were macrophage
      infiltration and necrosis, with less than half of the patients (41%) showing a
      significant lymphocytic response or a high ALVAL reaction (6%). Other
      morphological changes varied among patients and included hemosiderin
      accumulation, cartilage formation, and heterotopic ossification. Both scoring
      systems are useful for correlating macrophage and lymphocyte responses and for
      comparison with the other; however, given the diversity and variability of the
      current responses, the Oxford-ALVAL system is more suitable for scoring tissues
      from MOM THR patients revised for loosening. It is important that standardized
      methods of scoring MOM tissue responses be used consistently so multiple study
      results can be compared and a consensus can be generated. 

PMID- 24941404
TI  - Metal sensitivities among TJA patients with post-operative pain: indications for
      multi-metal LTT testing.
AB  - Metal sensitivity testing is generally the diagnosis method of last resort for
      aseptic painful implants with elevated inflammatory responses. However, the
      relationship between implant-related pain and implant-debris-related metal
      sensitization remains incompletely understood. Although a sensitivity to nickel
      alone has been used as a general measure of metal allergy, it may lack the
      specificity to correlate sensitivity to specific implant metals and thus to
      select a biologically appropriate implant material. In this retrospective study,
      we report the incidence of pain and nickel sensitivity in patients with total
      joint arthroplasties (TJAs) referred for metal sensitivity testing (n=2018). We
      also correlated the degree of nickel hypersensitivity to implant pain levels
      (none, mild, moderate, and high, using a scale of 0-10) and the incidence of
      sensitivity to alternative implant metals in highly nickel-reactive subjects.
      Most patients (>79%) reported pain levels that were moderate to high regardless
      of implant age, whereas patients with severely painful TJAs had a statistically
      greater incidence of nickel sensitivity over the short-term post-operative period
      (<=4 years). Patients with moderate pain scores (4-7) and high pain scores (>=8)
      also exhibited significantly higher sensitivity to nickel compared to patients
      with no pain and no implant (controls) (p<0.05). Highly nickel-sensitive subjects
      (SI>8) also showed incidences of sensitization to alternative materials such as
      cobalt, chromium, or molybdenum (57%) or aluminum or vanadium alloy (52%). These
      data suggest that painful TJAs caused by metal sensitivity more likely occur
      relatively early in the post-operative period (<=4 years). The incidences of
      sensitivity to alternative implant metals in only a subset of nickel-reactive
      patients highlights the importance of testing for sensitization to all potential
      revision implant materials. 

PMID- 24941405
TI  - Effect of UHMWPE particle size, dose, and endotoxin on in vitro macrophage
      response.
AB  - Ultra-high molecular weight polyethylene wear debris generated by a prosthetic
      hip or knee has been linked to osteolysis and the limited lifespan of the
      implant. However, research results are conflicting with regard to which
      characteristics of the polyethylene wear debris are most inflammatory. The goal
      of this study was to determine whether particle size, number, and the presence of
      endotoxin significantly contribute to increased secretion of pro-inflammatory
      mediators by macrophages in vitro in response to polyethylene wear debris
      generated by a hip simulator. The results show that the prevailing inflammatory
      factor is endotoxin. The macrophages released only minimal levels of TNF-alpha
      and IL-6 in response to cleaned polyethylene particles, but these cytokines were
      released in significantly higher amounts in response to particles spiked with
      lipopolysaccharide (LPS). The number (up to 500 particles per cell) and size of
      the particles tested in this study had no significant influence on any of the
      measured outputs (macrophage viability, TNF-alpha, IL-6, or PGE2) unless
      associated with LPS.

PMID- 24941406
TI  - Effects of gelsolin on macrophage inflammatory responses to orthopaedic implant
      wear debris.
AB  - The local effects of implant wear debris on surrounding tissue has been a major
      focus of many investigators. Although there have been improvements in implants,
      significant numbers of revision surgeries are performed to address these issues.
      Gelsolin (GSN) is a protein in the cytoplasm and circulating serum involved in
      actin breakdown as well as anti-inflammatory processes. In this study, we tested
      the hypothesis that GSN in the presence of wear debris in vitro decreases the
      inflammatory response of a human monocyte cell line. We utilized titanium-,
      polyethylene-, and cobalt-characterized wear particles in a 1:100 and a 1:500
      cell-to-particle ratios in the presence of a low (0.2 uM) and normal (2.0 uM)
      concentrations of GSN and compared the inflammatory response to cells without GSN
      exposure. The results show that IL-6, IL-1, TNF-alpha, and PGE2 all increased
      with higher concentrations of GSN. Although the anti-inflammatory properties of
      GSN were not seen in this in vitro experiment, it has previously been shown that
      GSN does affect the inflammatory response of monocytes to orthopedic implant wear
      debris. The dose-response curve for GSN may have a bimodal profile, which should
      be further investigated.

PMID- 24941407
TI  - Design of a tribocorrosion bioreactor for the analysis of immune cell response to
      in situ generated wear products.
AB  - Adverse local tissue reactions to wear debris and corrosion products have lead to
      a sharp decline in the use of metal-on-metal (MOM) total hip athroplasties (THAs)
      clinically. Today, approximately 1 million patients are still carrying such a
      device. To gain a better understanding of the effect of wear and corrosion
      products on cells within the joint environment, it is important to generate
      conditions in vitro that resemble the in vivo system as closely as possible. In
      this paper, we present a novel tribocorrosion bioreactor that enables the
      simultaneous conduction of tribocorrosion and cell-culture experiments. In this
      setup, macrophage cell cultures are located in direct proximity to a tribological
      interface mimicking the sliding conditions of THA and are exposed to wear and
      corrosion products as they are generated. These products may include meta-stable
      species and metallo-organic complexes that have not been considered in earlier
      studies. The combination of standard tribological, electrochemical, and
      biological techniques is associated with several challenges that are described
      here in detail. 

PMID- 24941408
TI  - Implant debris particle size affects serum protein adsorption which may
      contribute to particle size-based bioreactivity differences.
AB  - Biologic reactivity to orthopedic implant debris mediates long-term clinical
      performance of total joint arthroplasty implants. However, the reasons that some
      facets of implant debris (e.g., particle size, shape, base material, etc.) are
      more pro-inflammatory remain controversial. This precludes accurate prediction
      and optimal design of modern total joint replacements. We hypothesized that
      debris particle size can influence adsorbed protein film composition and affect
      subsequent bioreactivity. We measured size-dependent proteinfilm adsorption, and
      adsorbed protein-film-dependent cytokine release using equal surface areas of
      different sized cobalt-chromium alloy (CoCr-alloy) particles and in vitro
      challenge of human macrophages (THP-1 and human primary). Smaller (5 MUm
      diameter) versus larger (70 MUm diameter) particles preferentially adsorbed more
      serum protein in general (p<0.03), where higher molecular weight serum proteins
      consistent with IgG were identified. Additionally, 5-MUm CoCr-alloy particles pre
      coated with different protein biofilms (IgG vs. albumin) resulted in a difference
      in cytokine expression in which albumin-coated particles induced more TNF-alpha
      release and IgG-coated particles induced more IL-1beta release from human
      monocytes/macrophages. In these preliminary in vitro studies, we have
      demonstrated the capability of equal surface areas of different particle sizes to
      influence adsorbed protein composition and that adsorbed protein differences on
      identical particles can translate into complex differences in bioreactivity.
      Together, these findings suggest that adsorbed protein differences on different
      sized particles of the same material may be a contributing mechanism by which
      certain particles induce different reactivities. 

PMID- 24941409
TI  - Impairment of autophagy in endothelial cells prevents shear-stress-induced
      increases in nitric oxide bioavailability.
AB  - Autophagy is a lysosomal catabolic process by which cells degrade or recycle
      their contents to maintain cellular homeostasis, adapt to stress, and respond to
      disease. Impairment of autophagy in endothelial cells studied under static
      conditions results in oxidant stress and impaired nitric oxide (NO)
      bioavailability. We tested the hypothesis that vascular autophagy is also
      important for induction of NO production caused by exposure of endothelial cells
      to shear stress (i.e., 3 h * ~20 dyn/cm(2)). Atg3 is a requisite autophagy
      pathway mediator. Control cells treated with non-targeting control siRNA showed
      increased autophagy, reactive oxygen species (ROS) production, endothelial NO
      synthase (eNOS) phosphorylation, and NO production upon exposure to shear stress
      (p < 0.05 for all). In contrast, cells with >85% knockdown of Atg3 protein
      expression (via Atg3 siRNA) exhibited a profound impairment of eNOS
      phosphorylation, and were incapable of increasing NO in response to shear stress.
      Moreover, ROS accumulation and inflammatory cytokine production (MCP-1 and IL-8)
      were exaggerated (all p < 0.05) in response to shear stress. These findings
      reveal that autophagy not only plays a critical role in maintaining NO
      bioavailability, but may also be a key regulator of oxidant-antioxidant balance
      and inflammatory-anti-inflammatory balance that ultimately regulate endothelial
      cell responses to shear stress. 

PMID- 24941410
TI  - Nanoscale imaging by superresolution fluorescence microscopy and its emerging
      applications in biomedical research.
AB  - Superresolution microscopy, an ensemble of light microscopy methods developed
      with the aim of surpassing the resolution limit imposed by diffraction, has been
      at the forefront of imaging technology innovations in recent years. By harnessing
      advances in fluorophore photophysics, fluorescent protein engineering, optics,
      and image processing, rapid strides have been made in enhancing imaging
      resolution via 3 major approaches: structured illumination microscopy, stimulated
      emission depletion microscopy, and single-molecule localization microscopy. From
      a diffraction-limited resolution of ~250 nm, an improvement of more than an order
      of magnitude down to ~10 nm can now be attained, converging upon the size scale
      of the macromolecular building blocks of cells. This opens up the possibility of
      direct visualization of molecular-scale architecture and interactions of specific
      proteins in biological structures that are important to health and disease. Here,
      theoretical foundations and practical considerations of superresolution
      microscopy in 2- and 3-dimensional imaging are discussed, along with their recent
      applications in addressing biological questions. 

PMID- 24941411
TI  - The biomechanics of ACL injury: progresses toward prophylactic strategies.
AB  - Anterior cruciate ligament (ACL) injuries are highly prevalent during sporting
      activities. These injuries often are associated with maneuvers involving landing
      or sudden change in direction, which are thought to "destabilize" the knee joint
      and cause ACL rupture. ACL injuries can affect one's mobility and quality of life
      because of abnormal locomotion and consequent knee pain. This review presents key
      findings from prior biomechanics studies that aimed to understand ACL injury
      mechanisms. These studies, ranging from motion analyses and in vitro impact tests
      to knee finite element simulations and multibody dynamics musculoskeletal
      simulations, have collectively revealed the multifactorial nature of ACL injury
      mechanisms. Therefore, the second part of this review addresses the strong need
      to develop prophylactic strategies that can attenuate the factors involved in ACL
      injury mechanisms, such that the knee joint can be protected from ACL injuries.
      Previous studies have emphasized strategies such as knee bracing and strength
      training of important muscle groups. Although these strategies were intended to
      mitigate ACL injury-causing factors, their clinical outcomes remain
      controversial. Given the rapid progress of technologies in this area, however,
      the current state of uncertainty will gradually lead to prospective biomechanics
      research that can adopt a multifactorial approach toward protecting the ACL from
      injury. 

PMID- 24941412
TI  - Nanoparticle interface to biology: applications in probing and modulating
      biological processes.
AB  - Nanomaterials can be considered as "pseudo" subcellular entities that are similar
      to endogenous biomolecules because of their size and ability to interact with
      other biomolecules. The interaction between nanoparticles and biomolecules gives
      rise to the nano-bio interface between a nanoparticle and its biological
      environment. This is often defined in terms of the biomolecules that are present
      on the surface of the nanoparticles. The nano-bio interface alters the surface
      characteristics and is what the biological system sees and interacts with. The
      nanoparticle can thus be viewed as a "scaffold" to which molecules are attached.
      Intelligent design of this nano-bio interface is therefore crucial to the
      functionality of nanoscale systems in biology. In this review, we discuss the
      most common nano-bio interfaces formed from molecules including DNA, polymers,
      proteins, and antibodies, and discuss their applications in probing and
      modulating biological processes. We focus our discussion on the nano-bio
      interface formed on gold nanoparticles as our nanoparticle "scaffold" of interest
      in part because of our research interest as well as their unique physicochemical
      properties. While not exhaustive, this review provides a good overview of the
      latest advances in the use of gold nanomaterial interface to probe and modulate
      biological processes. 

PMID- 24941413
TI  - A review of lower extremity assistive robotic exoskeletons in rehabilitation
      therapy.
AB  - The rapid advancement of robotics technology in recent years has pushed the
      development of a distinctive field of robotic applications, namely robotic
      exoskeletons. Because of the aging population, more people are suffering from
      neurological disorders such as stroke, central nervous system disorder, and
      spinal cord injury. As manual therapy seems to be physically demanding for both
      the patient and therapist, robotic exoskeletons have been developed to increase
      the efficiency of rehabilitation therapy. Robotic exoskeletons are capable of
      providing more intensive patient training, better quantitative feedback, and
      improved functional outcomes for patients compared to manual therapy. This review
      emphasizes treadmill-based and over-ground exoskeletons for rehabilitation.
      Analyses of their mechanical designs, actuation systems, and integrated control
      strategies are given priority because the interactions between these components
      are crucial for the optimal performance of the rehabilitation robot. The review
      also discusses the limitations of current exoskeletons and technical challenges
      faced in exoskeleton development. A general perspective of the future development
      of more effective robot exoskeletons, specifically real-time biological synergy
      based exoskeletons, could help promote brain plasticity among neurologically
      impaired patients and allow them to regain normal walking ability. 

PMID- 24941414
TI  - Computer-assisted transoral surgery with flexible robotics and navigation
      technologies: a review of recent progress and research challenges.
AB  - This article reviews the flexible robotic surgery and navigation technologies
      that are currently available and under research development, in particular for
      transoral robotic surgery, in both broad and narrow senses. The clinical
      background, classifications, associated biomedical robotics applications, and
      surgical outcomes are illustrated in this new paradigm of minimally invasive
      surgery. The state-of-the-art robotic and navigation systems for transoral
      procedures are reviewed by identifying their key properties and considerations.
      The use of different materials and actuation methods by current robotic systems
      offers various movements for different purposes, and their characteristics are
      compared. The future research trends of robotic and navigation systems for
      transoral procedures are discussed in terms of emerging new material, actuation,
      and sensing technologies. 

PMID- 24941415
TI  - Recent advances in optical microscopy methods for subcellular imaging of thick
      biological tissues.
AB  - Optical microscopy has been widely applied in cellular and subcellular imaging.
      Conventional light microscopes, however, have rather limited imaging depth and
      are limited to imaging only mechanically sectioned thin samples. Multiphoton
      microscopy and optical coherence microscopy are common techniques for diffraction
      limited imaging beyond an imaging depth of 0.5 mm. Focal modulation microscopy is
      a novel method that combines confocal spatial filtering with focal modulation to
      reject out-of-focus backgrounds. Focal modulation microscopy has demonstrated an
      imaging depth comparable to those of multiphoton microscopy and optical coherence
      microscopy, near-real-time image acquisition, and capability with a multiple
      contrast mechanism. 

PMID- 24941416
TI  - Has percutaneous aortic valve replacement taken center stage in the treatment of
      aortic valve disease?
AB  - Modern biomedical advances have propelled percutaneous valve replacement into an
      effective and powerful therapy for many heart valve diseases, especially aortic
      valve stenosis. Experiences so far suggest that outcomes for new percutaneous
      valve replacement surgery compare favorably with that of traditional valve
      surgery in selected patients with severe symptomatic aortic stenosis. The
      inception of percutaneous aortic valve replacement (PAVR) began in 1992 when the
      potential for treating valve diseases was demonstrated through a modern technique
      of endoluminal deployment of a catheter-mounted crimped stented heart valve in an
      animal model. The first successful demonstration of such novel technique of
      surgical replacement of a heart valve was performed in 2002, when valve
      implantation in a patient with aortic stenosis was reported. Despite initial
      stumbles and a perception of being an uphill task, PAVR has emerged as one of the
      breakthroughs in surgical procedures. More than 1500 citations were found in
      PubMed, half of which were available after 2011. This is primarily because more
      than 50,000 procedures are being performed in more than 40 countries worldwide,
      with encouraging outcomes, and several stented valves have been launched in the
      market. This review provides a detailed analysis of the current state of the art
      of PAVR. Moreover, a competitive landscape of various devices available in the
      market and their design considerations, biomaterial selections, and overall
      hemodynamic performance are presented.

PMID- 24941417
TI  - Numerical simulations of deformation and aggregation of red blood cells in shear
      flow.
AB  - This article reviews numerical simulations of red blood cells (RBCs) mainly using
      the lattice Boltzmann method (LBM), focusing on the 2-dimensional deformation and
      aggregation of the cells in simple shear flow. We outline the incorporation of
      the immersed boundary method into the LBM, in which the membrane forces are
      obtained from the membrane model. The RBCs are simulated as a single biconcave
      capsule and as a doublet of biconcave capsules. The transition from swinging to
      tumbling motions of the RBCs, as induced by reducing the shear rate or increasing
      the membrane bending stiffness, is discussed. Also discussed is the aggregation
      tendency of the doublet of RBCs, for which homogenous deformability maintained
      RBC aggregation, whereas an increased deformability difference resulted in RBC
      dissociation. 

PMID- 24941419
TI  - The decade of action for road safety - progress in research.

PMID- 24941420
TI  - How do I know if I am normal?

PMID- 24941418
TI  - Shoulder problems in overhead sports. Part I - biomechanics of throwing.
AB  - The article discusses the biomechanical processes that occur during an overhead
      throw. This activity is highly specialized and requires full and proper function
      from the shoulder joint. It consists of active and passive stabilization and
      synchronous work of the accelerating and decelerating muscles. The process of the
      overhead throw can be divided into several phases that differ from each other in
      biomechanical parameters and involvement of specific muscles.

PMID- 24941421
TI  - Pyridyl-cyclodextrin for ultra-hydrosolubilization of [60]fullerene.
AB  - An efficient hydrosolubilizing reagent for [60]fullerene (C60) was newly
      developed with a gamma-cyclodextrin (gamma-CD) derivative having triazole
      methoxypyridyl moieties at its 6-hydroxyl positions (PCD). Through solid-state
      mechanochemical complexation, PCD forms a hydrosoluble inclusion complex of C60
      with a concentration of more than 70 mM. This is approximately 90 times greater
      than that with non-substituted gamma-CD prepared by the same method. 

PMID- 24941422
TI  - Solubilization of 1-hexanol in aqueous solutions of sodium dodecyl sulfate at
      pressures up to 140 MPa: partial molar volumes, compressibilities, and partition
      coefficients.
AB  - Partial molar volumes and partial molar compressibilities of aqueous solutions of
      sodium dodecyl sulfate (SDS) and 1-hexanol at pressure up to 140 MPa have been
      determined. For aqueous SDS solutions the partial molar compressibility increases
      with pressure below the cmc and decreases with pressure above the cmc. The
      partial molar compressibility of aqueous 1-hexanol increases with pressure. The
      increased partial molar compressibility reflects that the structure of water is
      gradually broken down by increased pressure. Thus, the negative effect of
      electrostriction around the charged parts of SDS decreases as do the effects of
      hydrophobic hydration around the CH2 groups. In the micellar state the
      compressibility of the aggregate is the main factor, becoming less compressible
      as pressure increases. The cmc of SDS, as determined by speed of sound
      measurements, increases with pressure and goes through a shallow maximum at about
      110 MPa. When 1-hexanol is added to SDS solutions, it will be partitioned between
      the aqueous and micellar (pseudo) phases. The partition coefficient has been
      determined from partial molar compressibilites, and it appears to decrease with
      pressure, reach a minimum around 80 MPa, and then increase, though the change
      with pressure is small. 

PMID- 24941427
TI  - Gd-containing conjugated polymer nanoparticles: bimodal nanoparticles for
      fluorescence and MRI imaging.
AB  - Aqueous bifunctional semiconductor polymer nanoparticles (SPNs), approximately 30
      nm in diameter (as measured from electron microscopy), were synthesised using
      hydrophobic conjugated polymers, amphiphilic phospholipids and a gadolinium
      containing lipid. Their fluorescence quantum yields and extinction coefficients
      were determined, and their MRI T1-weighted relaxation times in water were
      measured. The bimodal nanoparticles were readily taken up by HeLa and murine
      macrophage-like J774 cells as demonstrated by confocal laser scanning microscopy,
      and were found to be MRI-active, generating a linear relationship between T1
      weighted relaxation rates and gadolinium concentrations The synthesis is
      relatively simple, and can easily result in milligrams of materials, although we
      fully expect scale-up to the gram level to be easily realised.

PMID- 24941423
TI  - Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae
      by binding to penicillin binding protein 1a. A new paradigm in respiratory
      infection.
AB  - RATIONALE: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are
      major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated
      with severe and often fatal pneumonia but the molecular basis for this remains
      unclear. OBJECTIVES: To determine if interaction between RSV and pneumococci
      enhances pneumococcal virulence. METHODS: We used confocal microscopy and Western
      blot to identify the receptors involved in direct binding of RSV and pneumococci,
      the effects of which were studied in both in vivo and in vitro models of
      infection. Human ciliated respiratory epithelial cell cultures were infected with
      RSV for 72 hours and then challenged with pneumococci. Pneumococci were collected
      after 2 hours exposure and changes in gene expression determined using
      quantitative real-time polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS:
      Following incubation with RSV or purified G protein, pneumococci demonstrated a
      significant increase in the inflammatory response and bacterial adherence to
      human ciliated epithelial cultures and markedly increased virulence in a
      pneumonia model in mice. This was associated with extensive changes in the
      pneumococcal transcriptome and significant up-regulation in the expression of key
      pneumococcal virulence genes, including the gene for the pneumococcal toxin,
      pneumolysin. We show that mechanistically this is caused by RSV G glycoprotein
      binding penicillin binding protein 1a. CONCLUSIONS: The direct interaction
      between a respiratory virus protein and the pneumococcus resulting in increased
      bacterial virulence and worsening disease outcome is a new paradigm in
      respiratory infection.

PMID- 24941428
TI  - Dicyanomethylene-functionalized squaraine as a highly selective probe for
      parallel G-quadruplexes.
AB  - DNA sequences that can form G-quadruplexes (G4s) are highly prevalent in the
      genome. However, the structures and functions of most G4-forming sequences in the
      genome are poorly understood. Therefore, the development of molecular probes for
      G4 recognition in biological samples, especially probes with long wavelength, are
      important for the basic research of G4s. Squaraines dyes exhibit sharp and
      intense absorption and strong emission in the red to NIR region, but very few of
      them have been reported as probes for the recognition of nucleic acids. Here we
      report the interactions of two squaraine dyes, STS and CSTS, with different kinds
      of DNA. The dicyanomethylene-functionalized squaraine dye, CSTS, exhibits strong
      interaction with the parallel G4s, but no interaction with other DNA. In aqueous
      conditions, this interaction causes the transformation of CSTS from H-aggregates
      to monomers, which results in decline and growth of the absorption spectra of
      both forms. The parallel G4s enhance the fluorescence of both STS and CSTS, but
      the fluorescence enhancement of CSTS is much higher than that of STS. CSTS is
      demonstrated to bind to G4s through end-stacking model on G-quartet surface. The
      high selectivity of CSTS to parallel G4s is attributed to its V-shaped rigid
      planar pi scaffold. The high selectivity, very low background fluorescence, large
      absorption coefficient, and high fluorescence quantum yield make CSTS hold great
      promise as a long-wavelength probe for parallel G4 detection in biological
      samples or in vivo. 

PMID- 24941429
TI  - Efficacy of Multivitamin/mineral Supplementation to Reduce Chronic Disease Risk:
      A Critical Review of the Evidence from Observational Studies and Randomized
      Controlled Trials.
AB  - We reviewed recent scientific evidence regarding the effects of
      multivitamin/mineral (MVM) supplements on risk of chronic diseases, including
      cancer, cardiovascular disease, and age-related eye diseases. Data from
      randomized controlled trials (RCTs) and observational, prospective cohort studies
      were examined. The majority of scientific studies investigating the use of MVM
      supplements in chronic disease risk reduction reported no significant effect.
      However, the largest and longest RCT of MVM supplements conducted to date, the
      Physicians' Health Study II (PHS II), found a modest and significant reduction in
      total and epithelial cancer incidence in male physicians, consistent with the
      Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) trial. In
      addition, PHS II found a modest and significant reduction in the incidence of
      nuclear cataract, in agreement with several other RCTs and observational,
      prospective cohort studies. The effects of MVM use on other subtypes of cataract
      and age-related macular degeneration remain unclear. Neither RCTs nor prospective
      cohort studies are without their limitations. The placebo-controlled trial design
      of RCTs may be inadequate for nutrient interventions, and residual confounding,
      measurement error, and the possibility of reverse causality are inherent to any
      observational study. National surveys show that micronutrient inadequacies are
      widespread in the US and that dietary supplements, of which MVMs are the most
      common type, help fulfill micronutrient requirements in adults and children. 

PMID- 24941430
TI  - Effect of type 2 diabetes mellitus on pulmonary function.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disease with
      debilitating effects on multiple organs. The alveolar-capillary network in the
      lung is a large microvascular unit which may be affected by T2DM-associated
      microangiopathy. METHODS: This retrospective study investigated whether type 2
      diabetes mellitus (T2DM) affected pulmonary function. Of the 584 patients
      enrolled in the study, 292 had T2DM and 292 did not. Forced expiratory volume in
      one second (FEV1), forced vital capacity (FVC), maximum voluntary ventilation
      (MVV) and total lung capacity (TLC) are values as percent of predicted, as well
      as FEV1/FVC ratio which were values measured. RESULTS: FEV1, FVC, FEV1/FVC ratio,
      MVV, and TLC were significantly lower in T2DM than in non-T2DM (P-values <
      0.010). Multiple linear regression analysis found that for the entire study
      population fasting plasma glucose levels was negatively associated with FEV1,
      FVC, FEV1/FVC ratio and maximum voluntary ventilation (P-values < 0.030).
      Patients with T2DM were negatively associated with total lung capacity (P-values
      = 0.025). Multiple linear regression analysis found for patients with T2DM that
      fasting plasma glucose was negatively associated with FEV1, FVC, FEV1/FVC ratio
      and maximum voluntary ventilation (P-values < 0.020). In T2DM patient, height was
      negatively correlated with FEV1 and FVC (all P-values < 0.020), triglycerides
      were negatively correlated with FEV1/FVC ratio (P-values = 0.048), and creatinine
      was negatively correlated with total lung capacity (P-values = 0.017).
      CONCLUSIONS: In summary, T2DM is associated with impaired pulmonary function
      consistent with obstructive ventilation pattern and fasting plasma glucose is an
      independent risk factor of reduced pulmonary function.

PMID- 24941431
TI  - Comparison of nephron-protective effects of enalapril and GLP analogues
      (exenatide) in diabetic nephropathy.
AB  - BACKGROUND: One of the major concerns is a nephropathy in diabetes, which applies
      many different kinds of medicines. However, required level of the treatment of
      renal disease has not been achieved. AIM: To investigate and compare the effect
      of the enalapril and the exenatide on diabetic nephropathy in rats developed
      diabetes by streptozosin. MATERIAL AND METHODS: 32 male Sprague Dawley rats were
      divided into 4 groups: (1) Control, (2) Diabetic (DM), (3) DM+ Enalapril, and (4)
      DM+ exenatide groups. Then, the animals were euthanized and their blood samples
      were collected by cardiac puncture for blood glucose; blood urea nitrogen (BUN),
      creatinin, and nephrectomy were performed for histopathologic examination, and
      urine samples were taken on stick for proteinuria. RESULTS: Administration of the
      enalapril or the exenatide in diabetic rats resulted in a significant reduction
      both fibronectin, induced nitric oxide synthase (i-NOS) expression in glomerular
      area and urine protein levels. It was shown that both of enalapril and exenatide
      protected the renal glomerulus more than diabetic group in the nephropathy
      histopathologically. CONCLUSION: The beneficial effects of enalapril and
      exenatide which reduces fibronectin, i-NOS expression and urine protein levels or
      increases recovery of glomerules, might be used for preventing the harmful
      effects of diabetic nephropathy.

PMID- 24941432
TI  - Measurement of cortisol and testosterone in hair of obese and non-obese human
      subjects.
AB  - OBJECTIVE: Hair analysis has been demonstrated to accurately reflect exposure to
      drug abuse, environmental toxins and exogenous hormones. We tested the
      feasibility of measuring cortisol and testosterone in hair of healthy and obese
      subjects. MEASUREMENTS: A modified immunoassay (ELISA) originally developed for
      saliva was used. Hair, urine and blood samples were collected from young non
      obese and obese patients. Perceived stress (PSS) was measured using a validated
      questionnaire. RESULTS: There was no difference in PSS between non-obese and
      obese subjects. Hair cortisol levels were significantly correlated with weight (r
      = 0.27, p < 0.05) and systolic blood pressure (r = 0.28, p < 0.05), while the
      correlation with BMI did not reach statistical significance (p = 0.063). Hair
      cortisol levels did not correlate with age or urinary cortisol. There was a
      negative correlation between hair testosterone and age (r = -0.47, p < 0.05) and
      BMI (r = -0.40, p < 0.05). The correlation between hair testosterone and free
      androgen index (FAI) did not reach statistical significance (p = 0.098). The
      ratio of hair cortisol over hair testosterone (C/T) was higher in the obese group
      than in the young non-obese group. The C/T ratio correlated positively with age
      (r = 0.56, p < 0.01), waist circumference (r = 0.63, p < 0.01) and BMI (r = 0.62,
      p < 0.01), while the correlation between C/T ratio and FAI did not reach
      statistical significance. CONCLUSION: Hair cortisol levels increase, while hair
      testosterone levels decrease with obesity. The hair C/T ratio was significantly
      correlated with age, BMI and waist circumference better than hair cortisol or
      testosterone alone. As hair collection is non-invasive and is not influenced by
      moment-to-moment variations, the measurement of hormones in hair is a useful tool
      in research and possibly clinical practice.

PMID- 24941433
TI  - Impact of age and metabolic syndrome on the adipokine profile in childhood and
      adult obesity.
AB  - OBJECTIVE: Obesity triggers an inflammatory response characterized by elevated
      circulating pro-inflammatory adipokines that predisposes to T2DM and
      cardiovascular disease. The objective of our study was to determine a potential
      association of adipokine plasma profile and the presence of a MetS in obese
      children and adolescents compared to adults. DESIGN AND METHODS: We determined
      serum levels of the adipokines soluble CD163 (sCD163), fetuin-A, osteopontin
      (OPN) and interleukin-1 receptor antagonist (IL-1 Ra) in 30 pediatric and 36
      adult obese patients in a cross-sectional study. RESULTS: Serum concentrations of
      all tested adipokines except sCD163 were significantly elevated in the pediatric
      cohort compared to adults. Patients with MetS showed increased serum levels of
      sCD163, fetuin-A and IL-1 Ra levels compared to those without MetS. Fetuin-A and
      sCD163 remained significantly elevated by MetS within the juvenile group and
      borderline significant in the adults when tested separately. In the pediatric
      cohort we found correlations between sCD163 and fetuin-A as well as OPN and IL-1
      Ra whereas correlations of sCD163 and both fetuin-A and IL-1 Ra were found in the
      adult group. CONCLUSION: Our results indicate that adipokine profiles related to
      the presence of MetS significantly differ between pediatric and adult patients
      which may point to different underlying mechanisms.

PMID- 24941434
TI  - Hepatic dysfunction related to thyrotropin receptor antibody in patients with
      Graves' disease.
AB  - BACKGROUND: Hepatic dysfunction is a common phenomenon in patients with Graves'
      disease (GD). However, its pathogenesis is not fully understood. We aimed to
      determine the correlation between the thyrotropin receptor antibody (TRAb) and
      liver biochemical abnormalities in patients with GD. METHODS: A total of 236
      consecutive unrelated inpatients with newly diagnosed and untreated GD were
      included. Clinical characteristics (age, gender, disease duration) were
      collected. The liver biochemical values were tested and serum thyroid hormones,
      anti-thyroid antibodies and thyroid volumes were also evaluated. The patients
      were divided into hepatic dysfunction (HDF) and normal hepatic function (NHF)
      groups according to liver biochemical values. RESULTS: We found that 77.9%
      untreated patients with GD had at least one liver function test abnormality. The
      levels of TRAb in patients of HDF group were significantly increased compared
      with those in patients of NHF group, P < 0.001. Linear regression suggested that
      TRAb has significant correlation with AST, ALP, gamma-GTP, TB and DB. Logistic
      regression concluded that GD patients with high levels of TRAb had a greater
      possibility of developing liver biochemical abnormalities (OR = 1.069, 95% CI
      1.019-1.113). CONCLUSIONS: Hepatic dysfunction is common in patients with GD, and
      elevation of TRAb may contribute to hepatic dysfunction in patients with GD.

PMID- 24941435
TI  - Effects of acarbose on polycystic ovary syndrome: a meta-analysis.
AB  - OBJECTIVE: Whether or not acarbose benefits patients with polycystic ovary
      syndrome (PCOS) remains controversial. Therefore, we performed a meta-analysis to
      synthesize the literature regarding the therapeutic effects of acarbose on PCOS.
      METHODS: A comprehensive literature search was performed using terms, such as
      polycystic ovary syndrome, ovary polycystic disease, PCOS, hyperandrogenemia,
      acarbose, alpha-glucosidase inhibitors, and randomized controlled trials (RCTs),
      in the following bibliographic databases: Medline; Embase; and Cochrane
      Controlled Trials Register. The identified reference lists were checked manually.
      RESULTS: 6 RCTs met the inclusion criteria. Based on the meta-analysis of 3
      studies, acarbose was superior to placebo or no treatment in reducing serum
      levels of testosterone (Std MD = - 3.38, 95% CI:-5.97~-0.78, P = 0.01) and
      acarbose caused a significantly higher incidence of side effects, such as
      abdominal distention and diarrhea (OR = 23.78, 95% CI: 5.67~99.75, P < 0.0001).
      The changes in Ferriman-Gallwey score or body mass index (BMI) were not
      significant. Based on the meta-analysis of 2 studies, acarbose were superior to
      placebo or no treatment in reducing triglycerides (TG; WMD = -18.18, 95% CI:
      36.30~-0.06, P = 0.05) and very low-density lipoprotein (VLDL) cholesterol (WMD =
      - 6.49, 95% CI:-9.14~-3.84, P < 0.00001), and increasing high-density lipoprotein
      (HDL) cholesterol (WMD = 5.14, 95% CI:1.73~8.55, P = 0.003). There were no
      significant differences between acarbose and metformin with respect to
      improvements in ovulation rate, menstrual patterns, or changes in serum levels of
      testosterone, adverse events, or BMI. Heterogeneities were detected during the
      meta-analysis. CONCLUSIONS: This is the first meta-analysis to evaluate the role
      that acarbose plays in the treatment of PCOS. The currently available data showed
      that acarbose can reduce testosterone, TG, and VLDL, and increase HDL. Acarbose
      caused a significantly higher incidence of gastrointestinal disturbance. Given
      the small RCTs and poor quality of RCTs included, these results are not
      conclusive. A large-scale, randomized controlled study is needed to ascertain
      this uncertainty.

PMID- 24941436
TI  - Metallophilicity-driven dynamic aggregation of a phosphorescent gold(I)-silver(I)
      cluster prepared by solution-based and mechanochemical approaches.
AB  - We observed an unusual reversible aggregation process showing stimuli-responsive
      structural dynamics and optical changes attributed to the formation of a sandwich
      like Au3-Ag-Au3 cluster, which can be synthesized through both solution and
      mechanochemical methods. Unlike many other heteronuclear gold-silver clusters,
      the affinity of two cyclic Au3 complexes and a Ag(I) ion is solely bound by
      ligand unsupported Au-Ag bonding. The assembly/disassembly behavior, further
      forming nanoaggregates, is controllable by adjusting the concentration of the
      solution. In the solid state, the insertion of Ag(I) ion can be implemented
      through a mechanochemical approach, accompanied by visual color changes and
      reversible luminochromism. Furthermore, an uncommon solid-liquid extraction is
      demonstrated, showing the uniqueness of this labile Au-Ag metallophilicity and
      hinting at the possibility of manipulating a bonding process through a
      heterogeneous route. 

PMID- 24941437
TI  - Easily accessible polycyclic amines that inhibit the wild-type and amantadine
      resistant mutants of the M2 channel of influenza A virus.
AB  - Amantadine inhibits the M2 proton channel of influenza A virus, yet most of the
      currently circulating strains of the virus carry mutations in the M2 protein that
      render the virus amantadine-resistant. While most of the research on novel
      amantadine analogues has revolved around the synthesis of novel adamantane
      derivatives, we have recently found that other polycyclic scaffolds effectively
      block the M2 proton channel, including amantadine-resistant mutant channels. In
      this work, we have synthesized and characterized a series of pyrrolidine
      derivatives designed as analogues of amantadine. Inhibition of the wild-type M2
      channel and the A/M2-S31N, A/M2-V27A, and A/M2-L26F mutant forms of the channel
      were measured in Xenopus oocytes using two-electrode voltage clamp assays. Most
      of the novel compounds inhibited the wild-type ion channel in the low micromolar
      range. Of note, two of the compounds inhibited the amantadine-resistant A/M2-V27A
      and A/M2-L26F mutant ion channels with submicromolar and low micromolar IC50,
      respectively. None of the compounds was found to inhibit the S31N mutant ion
      channel.

PMID- 24941439
TI  - Does resilience predict suicidality? A lifespan analysis.
AB  - In this article, we examine the association between resilience and suicidality
      across the lifespan. Participants (n = 7485) from the Personality and Total
      Health (PATH) Through Life Project, a population sample from Canberra and
      Queanbeyan, Australia, were stratified into three age cohorts (20-24, 40-44, 60
      64 years of age). Binary Logistic regression explored the association between
      resilience and suicidality. Across age cohorts, low resilience was associated
      with an increased risk for suicidality. However, this effect was subsequently
      made redundant in models that fully adjusted for other risk factors for
      suicidality among young and old adults. Resilience is associated with suicidality
      across the lifespan, but only those in midlife continued to report increased
      likelihood of suicidality in fully-adjusted models.

PMID- 24941438
TI  - Nanostructured porous silicon-mediated drug delivery.
AB  - INTRODUCTION: The particular properties of nanostructured porous silicon (nanoPS)
      make it an attractive material for controlled and localized release of
      therapeutics within the body, aiming at increased efficacy and reduced risks of
      potential side effects. Since this is a rapidly evolving field as a consequence
      of the number of research groups involved, a critical review of the state of the
      art is necessary. AREAS COVERED: In this work, the most promising and successful
      applications of nanoPS in the field of drug delivery are reviewed and discussed.
      Two key issues such as drug loading and release are also analyzed in detail. The
      development of multifunctional (hybrid) systems, aiming at imparting additional
      functionalities to the nanoPS particles such as luminescence, magnetic response
      and/or plasmonic effects (allowing simultaneous tracking and guiding), is also
      examined. EXPERT OPINION: Nanostructured materials based on silicon are promising
      platforms for pharmaceutical applications given their ability to degrade and low
      toxicity. However, a very limited number of clinical applications have been
      demonstrated so far.

PMID- 24941440
TI  - Novel theranostic DNA nanoscaffolds for the simultaneous detection and killing of
      Escherichia coli and Staphylococcus aureus.
AB  - A novel theranostic platform is made by utilizing a self-assembled DNA
      nanopyramid (DP) as scaffold for incorporation of both detection and therapeutic
      moieties to combat bacterial infection. Red-emissive glutathione-protected gold
      nanoclusters (GSH-Au NCs) were used for bacterial detection. Actinomycin D (AMD)
      that was intercalated on the DP scaffold was used as therapeutic agent. This
      results in the formation of theranostic DPAu/AMD. Model bacteria Escherichia coli
      and Staphylococcus aureus were found to be readily taken in the DPAu/AMD and be
      susceptible to its killing effect. In addition, DPAu/AMD was observed to
      outperform the free AMD in killing infectious bacteria. The degradation of the DP
      structure by DNase was found to be responsible for the release of AMD and the
      effective killing effect of the infectious bacteria. This novel strategy presents
      a basic platform for future improvements to detect infectious bacteria and
      treatment. 

PMID- 24941442
TI  - The Coral Triangle Atlas: an integrated online spatial database system for
      improving coral reef management.
AB  - In this paper we describe the construction of an online GIS database system,
      hosted by WorldFish, which stores bio-physical, ecological and socio-economic
      data for the 'Coral Triangle Area' in South-east Asia and the Pacific. The
      database has been built in partnership with all six (Timor-Leste, Malaysia,
      Indonesia, The Philippines, Solomon Islands and Papua New Guinea) of the Coral
      Triangle countries, and represents a valuable source of information for natural
      resource managers at the regional scale. Its utility is demonstrated using
      biophysical data, data summarising marine habitats, and data describing the
      extent of marine protected areas in the region. 

PMID- 24941443
TI  - Behavioral and clinical characteristics of persons receiving medical care for HIV
      infection - Medical Monitoring Project, United States, 2009.
AB  - PROBLEM: As of December 31, 2009, an estimated 864,748 persons were living with
      human immunodeficiency virus (HIV) infection in the 50 U.S. states, the District
      of Columbia, and six U.S.-dependent areas. Whereas HIV surveillance programs in
      the United States collect information about persons with a diagnosis of HIV
      infection, supplemental surveillance systems collect in-depth information about
      the behavioral and clinical characteristics of persons receiving outpatient
      medical care for HIV infection. These data are needed to reduce HIV-related
      morbidity and mortality and HIV transmission. REPORTING PERIOD COVERED: Data were
      collected during June 2009-May 2010 for patients receiving medical care at least
      once during January-April 2009. DESCRIPTION OF THE SYSTEM: The Medical Monitoring
      Project (MMP) is an ongoing surveillance system that assesses behaviors and
      clinical characteristics of HIV-infected persons who have received outpatient
      medical care. For the 2009 data collection cycle, participants must have been
      aged >=18 years and have received medical care during January-April 2009 at
      sampled facilities that provide HIV medical care within participating MMP project
      areas. Behavioral and selected clinical data were collected using an in-person
      interview, and most clinical data were collected using medical record
      abstraction. A total of 23 project areas in 16 states and Puerto Rico were funded
      to collect data during the 2009 data collection cycle. The data were weighted for
      probability of selection and nonresponse to be representative of adults receiving
      outpatient medical care for HIV infection in the United States and Puerto Rico.
      Prevalence estimates are presented as weighted percentages. The period of
      reference is the 12 months before the patient interview unless otherwise noted.
      RESULTS: The patients in MMP represent 421,186 adults who received outpatient
      medical care for HIV infection in the United States and Puerto Rico during
      January-April 2009. Of adults who received medical care for HIV infection, an
      estimated 71.2% were male, 27.2% were female, and 1.6% were transgender. An
      estimated 41.4% were black or African American, 34.6% were white, and 19.1% were
      Hispanic or Latino. The largest proportion (23.1%) were aged 45-49 years. Most
      patients (81.1%) had medical coverage; 40.3% had Medicaid, 30.6% had private
      health insurance, and 25.7% had Medicare. An estimated 69.6% of patients had
      three or more documented CD4+ T-lymphocyte cell (CD4+) or HIV viral load tests.
      Most patients (88.7%) were prescribed antiretroviral therapy (ART), and 71.6% had
      a documented viral load that was undetectable or <=200 copies/mL at their most
      recent test. Among sexually active patients, 55.0% had documentation in the
      medical record of being tested for syphilis, 23.2% for gonorrhea, and 23.9% for
      chlamydia. Noninjection drugs were used for nonmedical purposes by an estimated
      27.1% of patients, whereas injection drugs were used for nonmedical purposes by
      2.1% of patients. Overall, 12.9% of patients engaged in unprotected sex with a
      partner of negative or unknown HIV status. Unmet supportive service needs were
      prevalent, with an estimated 22.8% in need of dental care and 12.0% in need of
      public benefits, including Social Security Income or Social Security Disability
      Insurance. Fewer than half of patients (44.8%) reported receiving HIV and
      sexually transmitted disease prevention counseling from a health-care provider.
      INTERPRETATION: The findings in this report indicate that most adults living with
      HIV who received medical care in 2009 were taking ART, had CD4+ and HIV viral
      load testing at regular intervals, and had health insurance or other coverage.
      However, some patients did not receive clinical services and treatment in
      accordance with guidelines. Some patients engaged in behaviors, such as
      unprotected sex, that increase the risk for transmitting HIV to sex partners, and
      some used noninjection or injection drugs or both. PUBLIC HEALTH ACTIONS: Local
      and state health departments and federal agencies can use MMP data for program
      planning to determine allocation of services and resources, guide prevention
      planning, assess unmet medical and supportive service needs, inform health-care
      providers, and help focus intervention programs and health policies at the local,
      state, and national levels.

PMID- 24941445
TI  - High-pressure vibrational and polymorphic response of 1,1-diamino-2,2
      dinitroethene single crystals: Raman spectroscopy.
AB  - Raman spectroscopy was used to examine the vibrational and polymorphic behavior
      of 1,1-diamino-2,2-dinitroethene (FOX-7) to elucidate its structural and chemical
      stability under high pressure. Measurements were performed on single crystals
      compressed in a diamond anvil cell, and data were obtained over the entire
      frequency range of FOX-7 Raman activity. Several new features were observed with
      increase of pressure: (i) new vibrational peaks and discontinuity in the shifts
      of the peaks at 2 and 4.5 GPa, (ii) apparent coupling or mixing of several modes,
      and (iii) changes in the NH2 stretching spectral shape and modes shift. The
      spectral changes at 2 GPa, in contrast to previous reports, involved only a few
      peaks and likely resulted from a small molecular transformation. In contrast,
      changes at 4.5 GPa involved most of the modes, and the pressure for the onset and
      completion of the changes depended on the pressure medium. A large pressure
      hysteresis regarding the changes at 4.5 GPa implies a reconstructive
      transformation. We suggest that this transformation reflects a change in the
      balance between interlayer (van der Waals) and in-layer (H-bonding) interactions.
      Despite these transformations, further compression to 40 GPa and subsequent
      release of pressure did not cause any irreversible changes. This finding implies
      that FOX-7 has remarkable chemical stability under high pressures. The observed
      coupling between the various modes with increasing pressure was analyzed within
      the Fermi resonance model. The potential implication of the coupling of modes for
      shock insensitivity of FOX-7 is briefly discussed. 

PMID- 24941444
TI  - Phosphoproteome profiling of the macrophage response to different toll-like
      receptor ligands identifies differences in global phosphorylation dynamics.
AB  - Toll-like receptors (TLRs) are among the first sensors that detect infection and
      drive immune response. Macrophages encountering a pathogen are usually stimulated
      not by one TLR, but by a combination of TLRs engaged by distinct microbe ligands.
      To understand the integrated signaling under complex conditions, we investigated
      the differences in the phosphoprotein signaling cascades triggered by TLR2, TLR4,
      and TLR7 ligands using a single responding cell population. We performed a
      global, quantitative, early poststimulation kinetic analysis of the mouse
      macrophage phosphoproteome using stable isotope labeling with amino acids coupled
      to phosphopeptide enrichment and high-resolution mass spectrometry. For each TLR
      ligand, we found marked elevation of phosphorylation of cytoskeleton components,
      GTPases of the Rho family, and phospholipase C signaling pathway proteins.
      Phosphorylation of proteins involved in phagocytosis was only seen in response to
      TLR2 and TLR4 but not to TLR7 activation. Changes in the phosphorylation of
      proteins involved in endocytosis were delayed in response to TLR2 as compared to
      TLR4 ligands. These findings reveal that the phosphoproteomic response to
      stimulation of distinct TLRs varies both in the major modification targets and
      the phosphorylation dynamics. These results advance the understanding of how
      macrophages sense and respond to a diverse set of TLR stimuli. 

PMID- 24941446
TI  - pH- and reduction-responsive polymeric lipid vesicles for enhanced tumor cellular
      internalization and triggered drug release.
AB  - Enhanced tumor cellular internalization and triggered drug release are two main
      concerns in the development of nanoparticles for antitumor drug delivery. In this
      article, a new kind of smart pH- and reduction-dual-responsive drug- loaded PEG
      coated polymeric lipid vesicle (PPLV) that can achieve both enhanced tumor
      cellular internalization and triggered drug release has been designed and
      prepared. The PPLVs were formed from amphiphilic dextran derivatives. The
      antitumor drug, doxorubicin (DOX), was loaded in the cores of the PPLVs. The
      newly developed PPLVs had a nanosized structure (~40 nm) with PEG coating, so
      they were neutral and had high colloidal stability in the blood circulation. The
      in vitro physicochemical characterizations showed that the PPLVs lose their PEG
      coating and expose the positive surface charge under acidic environments. The in
      vitro cellular uptake study indicated that the acidic-treated PPLVs can
      efficiently enter tumor cells. It has been demonstrated by in vitro DOX release
      profiles that the PPLVs can achieve a triggered drug release in response to the
      reduction environment. The MTT assay demonstrated that DOX-loaded PPLVs treated
      with pH 5.0 solution had higher antitumor activity than DOX-loaded PPLVs treated
      with pH 7.4 solution. These results suggested that the PPLVs were promising
      nanoparticles for smart antitumor drug delivery applications. 

PMID- 24941448
TI  - Stabilization by Si substitution of the pseudobinary compound Gd(2)(Co(3-x)Si(x))
      with magnetocaloric properties around room temperature.
AB  - We report the discovery of a new solid solution Gd2(Co3-xSix) with 0.29 < x <
      0.50 in the Gd-Co-Si ternary system. Members of this solid solution crystallize
      with the La2Ni3-type structure and correspond to the stabilization of "Gd2Co3"
      through silicon substitution. The structure of the member Gd2(Co2.53(3)Si0.47)
      was determined by X-ray diffraction on a single crystal. It crystallizes with the
      space group Cmce and cell parameters a = 5.3833(4), b = 9.5535(6), and c =
      7.1233(5) A. Co/Si mixing is observed on two crystallographic positions. All
      compounds studied in the solid solution present a ferrimagnetic order with a
      strong composition-dependent Curie temperature TC with 280 K < TC < 338 K. The
      magnetocaloric effect, which amounts to around 1.7 J K(-1) kg(-1) for DeltaH = 2
      T, is interestingly tunable around room temperature over a temperature span of 60
      K through only 4-5% of composition change. 

PMID- 24941449
TI  - Spindle cell carcinoma of the breast in a patient with neurofibromatosis type 1.

PMID- 24941447
TI  - Fruit and vegetable intake and body mass index in a large sample of middle-aged
      Australian men and women.
AB  - Dietary guidelines around the world recommend increased intakes of fruits and non
      starchy vegetables for the prevention of chronic diseases and possibly obesity.
      This study aimed to describe the association between body mass index (BMI) and
      habitual fruit and vegetable consumption in a large sample of 246,995 Australian
      adults aged 45 + year who had been recruited for the "45 and Up" cohort study.
      Fruit and vegetable intake was assessed using validated short questions, while
      weight and height were self-reported. Multinomial logistic regression was used,
      by sex, to assess the association between fruit and vegetable intake and BMI.
      Compared to the referent normal weight category (BMI 18.5 to 24.9), the odds
      ratio (OR) of being in the highest vegetable intake quartile was 1.09 (95%
      confidence interval (CI) 1.04-1.14) for overweight women (BMI 25.0-29.9) and 1.18
      (95% CI 1.12-1.24) for obese women. The association was in the opposite direction
      for fruit for overweight (OR 0.85; 95% CI 0.80-0.90) and obese women (OR 0.75;
      95% CI 0.69-0.80). Obese and overweight women had higher odds of being in the
      highest intake quartile for combined fruit and vegetable intake, and were more
      likely to meet the "2 and 5" target or to have five or more serves of fruit and
      vegetables per day. In contrast, overweight men were less likely to be in high
      intake quartiles and less likely to meet recommended target of 5 per day, but
      there was no consistent relationship between obesity and fruit and vegetable
      intake. Underweight women and underweight men were less likely to be in the
      highest intake quartiles or to meet the recommended targets. These data suggest
      that improving adherence to dietary targets for fruit and vegetables may be a
      dietary strategy to overcome overweight among men, but that overweight and obese
      women are already adhering to these targets. The association between fruit and
      vegetable intake and underweight in adults suggests that improving fruit and
      vegetables intakes are important for the overall dietary patterns of people in
      this group. 

PMID- 24941450
TI  - Photochemistry of a dual-bacteriorhodopsin system in Haloarcula marismortui:
      HmbRI and HmbRII.
AB  - Recently, a dual-bacteriorhodopsin system, containing HmbRI and HmbRII, has been
      found in Haloarcula marismortui (Mol. Microbiol. 2013, 88, 551-561), and the
      light-driven proton pump activities were intrinsically different in a wide pH
      range. Compared with bacteriorhodopsin in H. salinarum (HsbR), the identical
      steady-state absorption contours of HsbR and HmbRs in the visible range indicated
      similarities in the retinal pocket. In addition, other reactive residues,
      including the proton relay channel, proton release group, and proton collecting
      funnel at the cytoplasm, were mostly conserved. We employed transient absorption
      spectroscopy and global analysis to characterize the photocycle intermediates and
      kinetics of HmbRI and HmbRII in the pH range of 4-8. The features of the time
      resolved difference spectra of HmbRI indicated that the photocycle of HmbRI
      mainly followed the conventional pathway, including intermediates M, N, and O. A
      minute bypassed pathway from intermediate M needed to be included to better match
      the experimental data. The corresponding intermediate M' is attributed to the all
      trans deprotonated Schiff base retinal, indicating the occurrence of retinal
      reisomerization prior to the reprotonation of the deprotonated Schiff base
      following the decay of intermediate M. Regarding HmbRII, its photocycle only
      followed the intermediates M and N, without intermediate O. The plausible
      molecular mechanisms, including the effects of the lengths of the loops and the
      distribution of the charged residues in the bacterio-opsin interior, were
      proposed to explain the differences in the photocycles. The pH-dependent
      photocycles were also investigated, and the results supported our proposed
      mechanism. Unravelling the photocycles of the HmbRs in the Haloarcula marismortui
      provided evidence that not only expanding the functional pH ranges but also the
      turnover kinetics are the strategies of the dual-bR system in the evolution of
      microbes in extreme environments. 

PMID- 24941451
TI  - Microwave irradiation induced changes in protein molecular structures of barley
      grains: relationship to changes in protein chemical profile, protein
      subfractions, and digestion in dairy cows.
AB  - The objectives of this study were to evaluate microwave irradiation (MIR) induced
      changes in crude protein (CP) subfraction profiles, ruminal CP degradation
      characteristics and intestinal digestibility of rumen undegraded protein (RUP),
      and protein molecular structures in barley (Hordeum vulgare) grains. Samples from
      hulled (n = 1) and hulless cultivars (n = 2) of barley, harvested from four
      replicate plots in two consecutive years, were evaluated. The samples were either
      kept as raw or irradiated in a microwave for 3 min (MIR3) or 5 min (MIR5).
      Compared to raw grains, MIR5 decreased the contents of rapidly degradable CP
      subfraction (from 45.22 to 6.36% CP) and the ruminal degradation rate (from 8.16
      to 3.53%/h) of potentially degradable subfraction. As a consequence, the
      effective ruminal degradability of CP decreased (from 55.70 to 34.08% CP) and RUP
      supply (from 43.31 to 65.92% CP) to the postruminal tract increased. The MIR
      decreased the spectral intensities of amide 1, amide II, alpha-helix, and beta
      sheet and increased their ratios. The changes in protein spectral intensities
      were strongly correlated with the changes in CP subfractions and digestive
      kinetics. These results show that MIR for a short period (5 min) with a lower
      energy input can improve the nutritive value and utilization of CP in barely
      grains. 

PMID- 24941452
TI  - Intra- and interlaboratory reliability of a cryopreserved trout hepatocyte assay
      for the prediction of chemical bioaccumulation potential.
AB  - Measured rates of intrinsic clearance determined using cryopreserved trout
      hepatocytes can be extrapolated to the whole animal as a means of improving
      modeled bioaccumulation predictions for fish. To date, however, the intra- and
      interlaboratory reliability of this procedure has not been determined. In the
      present study, three laboratories determined in vitro intrinsic clearance of six
      reference compounds (benzo[a]pyrene, 4-nonylphenol, di-tert-butyl phenol,
      fenthion, methoxychlor and o-terphenyl) by conducting substrate depletion
      experiments with cryopreserved trout hepatocytes from a single source. O
      terphenyl was excluded from the final analysis due to nonfirst-order depletion
      kinetics and significant loss from denatured controls. For the other five
      compounds, intralaboratory variability (% CV) in measured in vitro intrinsic
      clearance values ranged from 4.1 to 30%, while interlaboratory variability ranged
      from 27 to 61%. Predicted bioconcentration factors based on in vitro clearance
      values exhibited a reduced level of interlaboratory variability (5.3-38% CV). The
      results of this study demonstrate that cryopreserved trout hepatocytes can be
      used to reliably obtain in vitro intrinsic clearance of xenobiotics, which
      provides support for the application of this in vitro method in a weight-of
      evidence approach to chemical bioaccumulation assessment. 

PMID- 24941455
TI  - Presence of nanoparticles in wash water from conventional silver and nano-silver
      textiles.
AB  - Questions about how to regulate nanoenhanced products regularly arise as
      researchers determine possible nanoparticle transformation(s). Focusing concern
      on the incorporation and subsequent release of nano-Ag in fabrics often
      overshadows the fact that many "conventional silver" antimicrobials such as ionic
      silver, AgCl, metallic Ag, and other forms will also form different species of
      silver. In this study we used a laboratory washing machine to simulate the
      household laundering of a number of textiles prepared with known conventional Ag
      or nano-Ag treatments and a commercially available fabric incorporating yarns
      coated with bulk metallic Ag. Serial filtration allowed for quantification of
      total Ag released in various size fractions (>0.45 MUm, < 0.45 MUm, <0.1 MUm, and
      <10 kDa), while characterization of particles with TEM/EDX provided insight on Ag
      transformation mechanisms. Most conventional Ag additives yielded more total Ag
      and more nanoparticulate-sized Ag in the washing liquid than fabrics that used
      nano-Ag treatments. Incorporating nano-silver into the fiber (as opposed to
      surface treatments) yielded less total Ag during fabric washing. A variety of
      metallic Ag, AgCl, and Ag/S particles were observed in washing solution by
      TEM/EDX to various extents depending on the initial Ag speciation in the fabrics.
      Very similar particles were also observed when dissolved ionic Ag was added
      directly into the washing liquid. On the basis of the present study, we can state
      that all silver-treated textiles, regardless of whether the treatment is
      "conventional" or "nano", can be a source of silver nanoparticles in washing
      solution when laundering fabrics. Indeed, in this study we observed that textiles
      treated with "conventional" silver have equal or greater propensity to form nano
      silver particles during washing conditions than those treated with "nano"-silver.
      This fact needs to be strongly considered when addressing the risks of nano
      silver and emphasizes that regulatory assessment of nano-silver warrants a
      similar approach to conventional silver. 

PMID- 24941454
TI  - Protective role of thymoquinone against liver damage induced by tamoxifen in
      female rats.
AB  - One of the major reasons for terminating a clinical trial is the liver toxicity
      induced by chemotherapy. Tamoxifen (TAM) is an anti-estrogen used in the
      treatment and prevention of hormone-dependent breast cancer. Tamoxifen therapy
      may cause hepatic injury. The seeds of Nigella sativa, which contain the active
      ingredient thymoquinone (TQ), have been used in folk medicine for diverse
      ailments. TQ is reported to possess anticancer and hepatoprotective effects. In
      this study, the protective effects of TQ against TAM-induced hepatotoxicity in
      female rats were evaluated. Four groups of rats were used: control; TAM; TQ;
      TAM+TQ. TAM (45 mg.(kg body mass)(-1).day(-1), by intraperitoneal injection
      (i.p.), for 10 consecutive days) resulted in elevated serum levels of alanine
      aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate
      dehydrogenase, total bilirubin, and gamma glutamyl transferase, as well as
      depletion of reduced glutathione in the liver and accumulation of lipid
      peroxides. Also, TAM treatment inhibited the hepatic activity of superoxide
      dismutase. Further, it raised the levels of tumor necrosis factor alpha in the
      liver and induced histopathological changes. Pretreatment with TQ (50 mg.(kg body
      mass)(-1).day(-1); orally, for 20 consecutive days, starting 10 days before TAM
      injection) significantly prevented the elevation in serum activity of the
      assessed enzymes. TQ significantly inhibited TAM-induced hepatic GSH depletion
      and LPO accumulation. Consistently, TQ normalized the activity of SOD, inhibited
      the rise in TNF-alpha and ameliorated the histopathological changes. In
      conclusion, TQ protects against TAM-induced hepatotoxicity. 

PMID- 24941453
TI  - Dissociable contributions of ventromedial prefrontal and posterior parietal
      cortex to value-guided choice.
AB  - Two long-standing traditions have highlighted cortical decision mechanisms in the
      parietal and prefrontal cortices of primates, but it has not been clear how these
      processes differ, or when each cortical region may influence behaviour. Recent
      data from ventromedial prefrontal cortex (vmPFC) and posterior parietal cortex
      (PPC) have suggested one possible axis on which the two decision processes might
      be delineated. Fast decisions may be resolved primarily by parietal mechanisms,
      whereas decisions made without time pressure may rely on prefrontal mechanisms.
      Here, we report direct evidence for such dissociation. During decisions under
      time pressure, a value comparison process was evident in PPC, but not in vmPFC.
      Value-related activity was still found in vmPFC under time pressure. However,
      vmPFC represented overall input value rather than compared output value. In
      contrast, when decisions were made without time pressure, vmPFC transitioned to
      encode a value comparison while value-related parameters were entirely absent
      from PPC. Furthermore, under time pressure, decision performance was primarily
      governed by PPC, while it was dominated by vmPFC at longer decision times. These
      data demonstrate that parallel cortical mechanisms may resolve the same choices
      in differing circumstances, and offer an explanation of the diverse neural
      signals reported in vmPFC and PPC during value-guided choice. 

PMID- 24941456
TI  - Problems of the glenohumeral joint in overhead sports - literature review. Part
      II - pathology and pathophysiology.
AB  - In throwing sports shoulder is exposed to enormous and often repetitive
      overloads. Some sports (contact sports) are also connected with direct trauma. We
      are thus dealing with traumatic injuries, overload and degenerative damage. The
      article discusses the most frequent injuries of the shoulder characteristic for
      throwing sports. These are mainly disorders of arm rotation, internal
      impingement, lesion of the labrum (SLAP) and rotator cuff tears (PASTA).

PMID- 24941457
TI  - Contamination-free solutions of selenium in amines for nanoparticle synthesis.
AB  - We present, for the first time, versatile solutions of concentrated selenium,
      within an array of amines, in a fast and low temperature manner without
      contaminants. These solutions allow the unprecedented opportunity to synthesize a
      variety of pure selenium and selenide nanoparticles as well as mixed chalcogen
      sulfoselenide compounds. 

PMID- 24941458
TI  - [Characteristics and health care pathways of HIV-infected patients in Mayotte
      (1990-2010)].
AB  - OBJECTIVES: To evaluate the characteristics of HIV-infected patients treated in
      Mayotte, focusing on health care pathways. METHODS: Observational study, with
      retrospective collection of data from medical charts according to a standardized
      questionnaire. All HIV-infected patients who consulted at the Centre Hospitalier
      de Mayotte from 1990 through 2010 were included. Patients were classified as lost
      to follow-up if they had not consulted for at least 6 months and if no
      information about their outcome was available. Variables associated with loss to
      follow-up were analyzed by bivariate analysis (Chi(2)), and then multivariate
      analysis (logistic regression). RESULTS: Overall, 236 patients were enrolled (134
      females, 102 males), with a mean age of 30.7 +/- 12 years, and a median CD4 cell
      count of 390/mm(3) at diagnosis. HIV testing was most often ordered because of:
      i) HIV-related symptoms (n = 70); ii) risk factors (n = 67); iii) pregnancy (n =
      51). The 52 patients (22%) lost to follow-up were less likely to have medical
      insurance (52% versus 67%, p = 0.05) or antiretroviral treatment (56% versus 71%,
      p = 0.04), and were more frequently aged younger than 15 years (15% versus 2%,
      p<0.001). On multivariate analysis, initial management at the Centre Hospitalier
      de Mayotte (OR 2.62 [1.09-6.29], p = 0.03, and the absence of antiretroviral
      treatment (OR 1.97 [1.00-3.89], p = 0.05) were significantly associated with loss
      to follow-up. CONCLUSION: The HIV epidemic in Mayotte follows an African pattern
      in terms of main transmission pathways, age and circumstances of diagnosis, but
      the median CD4 cell count at diagnosis is closer to the pattern in metropolitan
      France. The rate of patients lost to follow-up is high (22%), mostly linked to
      problems with access to care.

PMID- 24941459
TI  - Black physicians and the struggle for civil rights: lessons from the Mississippi
      experience: part 1: the forces for and against change.
AB  - The roles of black physicians in the South in the period leading up to the Civil
      Rights Act of 1964 and the Voting Rights Act of 1965 have not been fully
      disclosed. In Mississippi and elsewhere in the South, it is a story of
      disenfranchised professionals who risked life, limb, and personal success to
      improve the lot of those they served. This first of 2 articles on the subject
      provides an overview of the forces for and against the struggle for civil rights
      and social justice in medicine in the South. We use newly available data from
      Mississippi as a prime example. An understanding of these forces is essential to
      an understanding of medical education and medical practice in this period and
      helps explain why the South remains in last place in most indicators of health
      today. 

PMID- 24941460
TI  - The bone-implant interface - nanoscale analysis of clinically retrieved dental
      implants.
AB  - Evaluation of the fine structure of the bone-implant interface in humans is a
      prerequisite for a deepened understanding of structure-function relationships
      with nano-modified biomaterials. In this study, three clinically stable, yet
      retrieved, laser-modified dental implants were evaluated using histological and
      interface ultrastructural analyses. The cumulative results for all threads
      containing intact tissue showed remodeled Haversian bone with bone area and bone
      implant contact in excess of 85% and 80%, respectively. Collagen fibrils, laid
      down parallel to the surface oxide layer, were mineralized by plate-like
      crystallites of stoichiometrically relevant (Ca/P ratios 1.30-1.67) bone-apatite.
      An overlap of titanium, oxygen, calcium and phosphorus signals indicated the
      gradual intermixing of bone-apatite and the nano-rough surface oxide. These
      results suggest that bone bonding to nano-textured titanium implant surfaces is
      promoted in human jaw-bone after functional loading. FROM THE CLINICAL EDITOR: In
      this study, newly developed and laser-modified titanium dental implants
      demonstrate strong evidence for implant-osseo integration basen on the surface
      and chemical analysis of three clinically stable dental implants.

PMID- 24941461
TI  - Alginate-coated chitosan nanogels differentially modulate class-A and class-B CpG
      ODN targeting of dendritic cells and intracellular delivery.
AB  - CpG-oligodeoxynucleotides (CpG-ODNs) interact with dendritic cells (DCs), but
      evidence is less clear for CpG-ODN admixed with or incorporated into vaccine
      delivery vehicles. We loaded alginate-coated chitosan-nanogels (Ng) with class-A
      or class-B CpG-ODN, and compared with the same CpG-ODNs free or admixed with
      empty Ng. Experiments were performed on both porcine and human blood DC
      subpopulations. Encapsulation of class-A CpG-ODN (loading into Ng) strongly
      reduced the CpG-ODN uptake and intracellular trafficking in the cytosol; this was
      associated with a marked deficiency in IFN-alpha induction. In contrast,
      encapsulation of class-B CpG-ODN increased its uptake and did not influence
      consistently intracellular trafficking into the nucleus. The choice of CpG-ODN
      class as adjuvant is thus critical in terms of how it will behave with
      nanoparticulate vaccine delivery vehicles. The latter can have distinctive
      modulatory influences on the CpG-ODN, which would require definition for
      different CpG-ODN and delivery vehicles prior to vaccine formulation. FROM THE
      CLINICAL EDITOR: This basic science study investigates the role of class-A and
      class-B CpG-oligodeoxynucleotides loaded into alginate-coated chitosan nanogels,
      demonstrating differential effects between the two classes as related to the use
      of these nanoformulations as vaccine delivery vehicles.

PMID- 24941462
TI  - Short- and long-term distribution and toxicity of gold nanoparticles in the rat
      after a single-dose intravenous administration.
AB  - Surface chemistry plays an important role in gold nanoparticles (AuNPs) stability
      and biocompatibility, which are crucial for their implementation into the
      clinical setting. We evaluated short- (30 min) and long-term (28 days)
      biodistribution and toxicity of ~20 nm citrate- and pentapeptide CALNN-coated
      AuNPs after a single intravenous injection in rats. The pattern of AuNPs
      distribution in Cit- and CALNN-AuNPs-injected rats was very similar in the
      assessed time-points. Both AuNPs were quickly removed from the bloodstream and
      preferentially accumulated in the liver. At 28 days liver remained the main
      accumulation site but at significantly lower levels compared to those found at 30
      min. Spleen atrophy and hematological findings compatible with mild anemia were
      observed in CALNN-AuNPs-administered rats. Under our experimental conditions,
      surface coating had more impact on toxicity rather than on biodistribution of the
      AuNPs. Improvements in the design of capping peptides need to be done to increase
      biomedical applicability of peptide-coated AuNPs. FROM THE CLINICAL EDITOR: The
      biodistribution and toxicity of ~ 20 nm citrate- and pentapeptide CALNN-coated
      gold nanoparticles was investigated after a single intravenous injection in rats.
      Rapid clearance and hepatic accumulation was found at 30-minutes, whereas mild
      anemia and spleen atrophy was seen 28 days post injection. The authors also
      concluded that the toxicity was related to the capping proteins as opposed to the
      biodistribution of the particles, providing important suggestion for future
      design of gold nanoparticles.

PMID- 24941464
TI  - Radiation dose enhancement of gadolinium-based AGuIX nanoparticles on HeLa cells.
AB  - Radiation dose enhancement of high-Z nanoparticles is an active area of research
      in cancer therapeutics. When kV and MV energy photon beams interact with high-Z
      nanoparticles in a tumor, the release of secondary electrons can injure tumor
      cells, leading to a higher treatment efficacy than radiation alone. We present a
      study that characterizes the radiation dose enhancing effects of gadolinium-based
      AGuIX nanoparticles on HeLa cells. Our in vitro clonogenic survival assays showed
      an average dose enhancement of 1.54* for 220 kVp radiation and 1.15* for 6 MV
      radiation. The sensitivity enhancement ratio at 4 Gy (SER4Gy) was 1.54 for 220
      kVp and 1.28 for 6 MV, indicating that these nanoparticles may be useful for
      clinical radiation therapy. FROM THE CLINICAL EDITOR: This study characterized
      the radiation dose enhancing effects of gadolinium-based AGuIX nanoparticles on
      HeLa cells, showing clear effects at 220 kV as well as 6 MV, suggesting that
      after additional studies, these nanoparticles may be beneficial in human
      radiation therapy.

PMID- 24941463
TI  - Targeted delivery of vascular endothelial growth factor improves stem cell
      therapy in a rat myocardial infarction model.
AB  - Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been
      successful because of poor cell survival due in part to insufficient blood supply
      after myocardial infarction (MI). We hypothesize that targeted delivery of
      vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature
      in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes
      targeting overexpressed P-selectin in MI tissue were infused by tail vein
      immediately after MI. One week later, MSCs were injected intramyocardially. The
      cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC
      treatment. Targeted VEGF+MSC combination treatment showed highest attenuation in
      cardiac function loss. The combination treatment also increased blood vessel
      density (80%) and decreased collagen content in post-MI tissue (33%). Engraftment
      of MSCs in the combination treatment group was significantly increased and the
      engrafted cells contributed to the restoration of blood vessels. FROM THE
      CLINICAL EDITOR: VEGF immunoliposomes targeting myocardial infarction tissue
      resulted in significantly higher attenuation of cardiac function loss when used
      in combination with mesenchymal stem cells. MSCs were previously found to have
      poor ability to restore cardiac tissue, likely as a result of poor blood supply
      in the affected areas. This new method counterbalances that weakness by the known
      effects of VEGF, as demonstrated in a rat model.

PMID- 24941465
TI  - Multiphoton imaging of tumor biomarkers with conjugates of single-domain
      antibodies and quantum dots.
AB  - An ideal multiphoton fluorescent nanoprobe should combine a nanocrystal with the
      largest possible two-photon absorption cross section (TPACS) and the smallest
      highly specific recognition molecules bound in an oriented manner. CdSe/ZnS
      quantum dots (QDs) conjugated to 13-kDa single-domain antibodies (sdAbs) derived
      from camelid IgG or streptavidin have been used as efficient two-photon
      excitation (TPE) probes for carcinoembryonic antigen (CEA) imaging on normal
      human appendix and colon carcinoma tissue. The TPACS for some conjugates was
      higher than 49,000 GM (Goeppert-Mayer units), considerably exceeding that of
      organic dyes being close to the theoretical value of 50,000 GM calculated for
      CdSe QDs. The ratio of sdAb-QD emission to the autofluorescence for 800 nm TPE
      was 40 times higher than that for 457.9 nm one-photon excitation. TPE ensures a
      clear discrimination of CEA-overexpressing tumor areas from normal tissue.
      Oriented sdAb-QD conjugates are bright specific labels for detecting low
      concentrations of antigens using multiphoton microscopy. FROM THE CLINICAL
      EDITOR: This study demonstrates carcinoembryonic antigen imaging on normal human
      appendix and colon carcinoma tissue utilizing CdSe/ZnS quantum dots conjugated to
      streptavidin or to 13-kDa single-domain antibodies as efficient two-photon
      excitation probes.

PMID- 24941467
TI  - Mini-stroke: what should you do? The symptoms may be short-lived, but you should
      take them every bit as seriously as you would a true stroke.

PMID- 24941466
TI  - Application of heparin as a dual agent with antimalarial and liposome targeting
      activities toward Plasmodium-infected red blood cells.
AB  - Heparin had been demonstrated to have antimalarial activity and specific binding
      affinity for Plasmodium-infected red blood cells (pRBCs) vs. non-infected
      erythrocytes. Here we have explored if both properties could be joined into a
      drug delivery strategy where heparin would have a dual role as antimalarial and
      as a targeting element of drug-loaded nanoparticles. Confocal fluorescence and
      transmission electron microscopy data show that after 30 min of being added to
      living pRBCs fluorescein-labeled heparin colocalizes with the intracellular
      parasites. Heparin electrostatically adsorbed onto positively charged liposomes
      containing the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane and loaded
      with the antimalarial drug primaquine was capable of increasing three-fold the
      activity of encapsulated drug in Plasmodium falciparum cultures. At
      concentrations below those inducing anticoagulation of mouse blood in vivo,
      parasiticidal activity was found to be the additive result of the separate
      activities of free heparin as antimalarial and of liposome-bound heparin as
      targeting element for encapsulated primaquine. FROM THE CLINICAL EDITOR: Malaria
      remains an enormous global public health concern. In this study, a novel
      functionalized heparin formulation used as drug delivery agent for primaquine was
      demonstrated to result in threefold increased drug activity in cell cultures, and
      in a murine model it was able to provide these benefits in concentrations below
      what would be required for anticoagulation. Further studies are needed determine
      if this approach is applicable in the human disease as well.

PMID- 24941468
TI  - Ask the doctor. I am postmenopausal, and I've noticed that my belly isn't as flat
      as it once was, even though my weight hasn't changed much in the past 15 years
      and I am healthy. Is this change in shape something I am just going to have to
      get accustomed to, or can I do something about it?

PMID- 24941469
TI  - Ask the doctor.  I have just stopped taking a statin drug because it was causing
      muscle pain.  To control my cholesterol I'm now taking ground flaxseed and a
      daily red yeast rice pill.  Are these supplements effective for lowering
      cholesterol?

PMID- 24941470
TI  - Why you need a bone density scan.  This important test can warn you before you
      break a bone.

PMID- 24941471
TI  - Staying active when it's hard to move.  Arthritis and other mobility issues
      shouldn't stop you from getting the exercise you need.

PMID- 24941472
TI  - Tea: drink to your health?  Why daily tea time might be just the thing for your
      health.

PMID- 24941473
TI  - Vitamin and mineral supplements: do you need them? A recent review casts doubt on
      supplements for disease prevention. Are they still worth taking?

PMID- 24941474
TI  - New treatments for incontinence.  Find out which of the latest therapies are
      worth trying.

PMID- 24941475
TI  - New blood pressure guidelines released.

PMID- 24941476
TI  - Lose a few pounds to help your heart.

PMID- 24941477
TI  - Older women with heart disease more likely to have memory problems.

PMID- 24941478
TI  - Drug cuts breast cancer risk by more than half.

PMID- 24941479
TI  - [The Italian Society of Nephrology].

PMID- 24941480
TI  - [The value of the utility of estimating QALYs: an open question].

PMID- 24941481
TI  - Protein intake in chronic renal failure revisited.

PMID- 24941482
TI  - [A case of hypercalcemia in hemodialysis].
AB  - We report a case of hypercalcemia in a female patient who was restarted on
      hemodialysis 22 years after renal transplantation. Graft biopsy showed chronic
      post-transplant nephropathy. Treatment with immunosuppressants and steroids was
      maintained owing to residual graft function. She was then given oral paracalcitol
      1 ug/d for secondary hyperparathyroidism (iPTH 850 pg/mL) and her transplant
      medication was reduced and then discontinued. After this, the patient referred
      widespread joint pain, especially in the hips and subsequently presented with
      erythema nodosum. She also developed hypercalcemia and hyperphosphatemia which
      persisted after stopping paracalcitol. The clinical picture of increased serum
      calcitriol, with depressed PTH, suggested sarcoidosis, despite normal ACE levels,
      a chest X-ray and skin biopsy confirmed the diagnosis, and the patient was
      started on prednisone 50 mg/day, resulting in prompt normalization of both
      symptoms and blood chemistry. This is a rare case of hypercalcemia secondary to
      sarcoidosis in an uremic patient. The sarcoidosis was most likely suppressed by
      the transplant therapy and rapidly developed after this was suspended. Prompt
      diagnosis resulted in a good therapeutic response.

PMID- 24941484
TI  - [Treatment of ANCA-associated vasculitis ... 40 years later].

PMID- 24941485
TI  - [Laser Microdissection/Mass Spectrometry: far beyond the congo red].

PMID- 24941483
TI  - [HFR-AEQUILIBRIUM and intradialytic cardiovascular stability: results of the
      first multicenter study in Lazio].
AB  - Intradialytic hypotension (IDH) is a still-frequent and poorly-understood
      complication of haemodialysis. Haemofiltration has recently been shown to reduce
      the phenomenon of IDH. HFR-Aequilibrium adds to traditional HFR and is, in
      practice, a variant comprising endogenous re-infusion of haemodiafiltration with
      dialysate sodium concentration and ultrafiltration rate profiles elaborated by
      the 'Profiler' plasma sodium biofeedback system, and measurement of plasma sodium
      via the on-line Natrium sodium sensor.

PMID- 24941486
TI  - [The anti-corruption law and the code of conduct for civil servants].

PMID- 24941487
TI  - [The nephrologic spring].

PMID- 24941489
TI  - [No matter what color is the cat, as long as it can catch mice].

PMID- 24941488
TI  - Managing serum phosphate: a pragmatic approach.

PMID- 24941490
TI  - [The philosophical meaning of surviving is not enough].

PMID- 24941491
TI  - [Save Our NHS. At the start the project of the Foundation GIMBE].

PMID- 24941492
TI  - [Decide wisely: health technology assessment tool to govern innovation and
      disinvestment].

PMID- 24941493
TI  - [Children on peritoneal dialysis and enteral feeding: indications and outcomes].
AB  - Despite improvements in overall prognosis, in the quality of life and in growth
      targets, children on peritoneal dialysis are subject to a high risk of growth
      retardation, especially if the disease begins in the early stages of life. In
      these patients, spontaneous feeding often does not provide an adequate intake of
      nutrients and early start of enteral nutrition needs to be considered. An
      intensive nutritional approach should always be established early and can be
      technically achieved using either a naso-gastric tube or a gastrostomy. In Italy,
      the first approach often involves the use of a naso-gastric tube despite
      epidemiological data suggesting the superiority of gastrostomy when the required
      outcome is improvement in growth parameters. Particular attention should be paid
      to the technique of gastrostomy. Despite this intensive approach, not all
      patients achieve the desired outcome of adequate growth probably because not all
      the possible mechanisms involved have yet been discovered.

PMID- 24941494
TI  - [Genotype-phenotype correlation in ADPKD: a possible role for NGAL?].
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common genetic cause of chronic kidney disease (CKD) in adults. It is associated
      with both inter- and intra- familial variability, which can be explained by
      genetic heterogeneity, modifier genes and a genetic background. NGAL, a 25-kDa
      protein released from tubular cells after harmful stimuli, is a new biomarker.
      Recent studies suggest a possible role for NGAL in CKD. The aim of this study was
      to investigate NGAL in the context of genotype-phenotype correlation in ADPKD.
      METHODS: We measured plasma NGAL, creatinine (Cr), and urea in 18 ADPKD patients
      on dialysis (PKD1_TRS), 29 of their relatives with CKD stage II-III (PKD1_AMB),
      33 wild-type relatives (PKD1_WT), 12 subjects in CKD stage II-III with confirmed
      mutation in PKD2 and 30 healthy controls (CTR). Cr, urea and CysC were measured
      according to standard methods. Plasma NGAL was measured using point-of-care test.
      Estimated glomerular filtration rate (eGFR) was calculated with a 4-variable
      standardized-MDRD formula. RESULTS: Plasma NGAL, CysC, Cr and urea levels in
      PKD1_TRS were significantly higher than CTR (all with p<0,001). PKD1_TRS pts had
      significantly higher NGAL, CysC, Cr and Urea levels compared to PKD1_AMB and
      PKD1_WT. PKD1_AMB pts had higher NGAL, CysC, Urea and Cr levels compared to
      PKD1_WT relatives. NGAL CysC, Cr and urea values were similar between PKD1_WT and
      CTR (p>0.05). NGAL levels were not significantly different in ADPKD patients in
      CKD stage II-III with mutation in PKD1 or PKD2 (86 pg/mL, IQR 60-109 vs 82
      pg/mL,IQR 63-169). NGAL correlated well (all with p<0.001) with CysC (r=0.95), Cr
      (r=0.89), urea (r=0.76) and inversely with eGFR (r=-0.81). A strong correlation
      between CysC and residual renal function was observed (CysC/eGFR: r=-0.86;
      CysC/Cr: r=0.7; CysC/Urea: r=0.79, all with p<0.001). CONCLUSION: This is the
      first study to evaluate plasma NGAL in the context of genotype-phenotype
      correlation. In ADPKD, NGAL levels were higher in patients already on Renal
      Replacement Therapy (RRT) compared to their affected relatives not on RRT. WT
      relatives had normal NGAL and CysC levels: these could be considered a better CTR
      group because they share the same genetic background with ADPKD subjects. No
      differences were found in NGAL levels between PKD1 and PKD2 patients in CKD stage
      II-III. Furthermore, the results indicate that NGAL correlates closely with renal
      function and CysC levels.

PMID- 24941495
TI  - [Does post-infection glomerulonephritis exist?].

PMID- 24941496
TI  - [The Academy of Ideas: the initiative of young people for young people. Container
      of innovative projects?].

PMID- 24941497
TI  - [In memory of Manuela Ravelli].

PMID- 24941498
TI  - Neurotrophic factors. Preface.

PMID- 24941501
TI  - Perfectionsm. An impossible goal in diabetes management.

PMID- 24941502
TI  - Blood glucose self-monitoring. Part I: the gear.

PMID- 24941503
TI  - The benefits of mindful eating.

PMID- 24941504
TI  - Fast & fresh: Recipes for spring.

PMID- 24941505
TI  - What your doctor is reading. Dangers of young-onset type 2 diabetes.

PMID- 24941506
TI  - Diabetes definitions.

PMID- 24941507
TI  - Pot for tots: children and medical marijuana.

PMID- 24941509
TI  - Parenting efficacy and its relationship to the prevention of childhood obesity.
AB  - Childhood obesity has become a topic of interest for the health sciences research
      community due to the childhood obesity epidemic. Pediatric nurse practitioners
      are in the frontline of prevention for children who are obese or at risk of
      becoming obese. Serving in this role requires the nurses' ability to measure
      parenting practices, parents' inner beliefs, and parental control over their
      child's eating practices. Questionnaires and other tools are needed to understand
      parents' thoughts on how satisfied they are as parents, their locus of control in
      their parent-child relationship, and how competent they feel in the parenting
      role. Many parenting scales related to self-efficacy, competence, locus of
      control, and satisfaction have been developed over the past decades, but little
      research development has occurred in relation to child's eating behaviors within
      nursing. This article will review the current parent efficacy literature and
      examine its relationship to childhood obesity.

PMID- 24941508
TI  - Tyrosinemia type 1: an overview of nursing care.
AB  - Tyrosinemia type 1 (TT1) is an inherited metabolic disease that can be fatal when
      not detected early by newborn screening. In the past, children with TT1 had a
      poor prognosis due to organ failure and neurologic crisis during infancy. Recent
      improvements in newborn screening have changed the prognosis of affected
      children. Measurement of succinylacetone by tandem mass spectrometry provides
      early identification and the opportunity to manage TT1 as a chronic disease.
      Treatment includes genetic counseling, dietary management, pharmacotherapy,
      metabolic crisis prevention, and whole organ transplant. Nursing care is critical
      to successful management when it is based on a clear understanding of the
      pathophysiology. This overview of nursing care will provide specific
      recommendations to reduce complications and enhance the quality of life for
      children with TT1.

PMID- 24941510
TI  - Roles and responsibilities of the nursing scholar.
AB  - Scholarship is an important facet of the nursing profession. There are many
      components, virtues, and roles and responsibilities of a nursing scholar
      practicing in today's ever-changing health care environment. Scholarship was
      redefined by Boyer to include scholarly activities in addition to research.
      Boyer's Model of Scholarship includes four interrelated and overlapping domains
      of discovery, integration, application, and teaching. Each domain is explained
      with examples for the pediatric nurse scholar, which includes roles in academia
      as well as in the practice setting. Pediatric nurses are key to scholarship in
      nursing because they work to improve the care of children.

PMID- 24941511
TI  - Understanding sleep during adolescence.
AB  - Adolescents have unique sleep behaviors related to physiological and
      developmental differences. Research suggests that sleep debt related to these
      adolescent differences contributes to risk for accidents, behavioral changes, and
      other health concerns. In addition, the impact of pain related to trauma,
      surgery, and chronic illness can further alter the sleep patterns of this age
      group. Limited normative parameters describe the sleep of healthy adolescents. A
      comparative study of 26 adolescents from 12 through 18 years of age was designed
      to describe the sleep patterns of two groups of adolescents. Sleep parameters,
      including actual sleep time, sleep efficiency, nighttime awakenings, and other
      sleep patterns of adolescents following post-operative tonsillectomy and
      adenoidectomy (T & A), were compared with an age and gender-matched sample of
      healthy adolescents. All adolescents wore wrist-actigraphy and documented sleep
      information in a diary for three continuous days. Healthy adolescents had
      significantly less (p = 0.003) actual hours of night time sleep and significantly
      less (p = 0.039) sleep efficiency than adolescents in the post-operative sample
      during the three days. None of the adolescents in this study had sufficient
      actual hours of nighttime sleep. Findings support the need for nurses to assess
      adolescent sleep patterns and to educate teens and their families about the
      importance of adequate sleep. Further research is needed to establish sleep
      interventions that will improve the sleep hygiene of both healthy adolescents and
      those who experience sleep disruption due to painful conditions.

PMID- 24941512
TI  - Choosing a design.

PMID- 24941513
TI  - Birth fathers: unequal power and myths in the Terry Achane case.

PMID- 24941514
TI  - (In)visible parents.

PMID- 24941515
TI  - Unions in optometry: introduction.

PMID- 24941516
TI  - Historical note on distance test charts and projectors.
AB  - The first documented letter distance test charts appeared in the 19th century.
      The first electronic projectors for eye and vision examination arrived in the
      early 20th century. This paper comments on some of those and other developments
      in distance testing charts and projectors. Brief biographical information is
      given on some of the inventors of projector systems.

PMID- 24941517
TI  - Ophthalmic comanagement and optometry.

PMID- 24941518
TI  - Biographical note on Harold Solan (1921-2012), optometrist and learning
      disabilities researcher.
AB  - This paper gives a brief biographical sketch of the career of Harold A. Solan and
      discusses his five books.

PMID- 24941519
TI  - Louis l. DeMars and the DeMars School of Optometry.

PMID- 24941520
TI  - [Euthanasia, right to die and sacrifice].

PMID- 24941521
TI  - [Digital technology, a path to competent care].

PMID- 24941522
TI  - [Use of Biatain dressing in the management of acute wounds and chronic exudative
      wounds].

PMID- 24941523
TI  - [Observational study on the efficacy of TLC-Ag and TLC-NOSF on chronic wounds].

PMID- 24941525
TI  - [Thinking differently about physical handicaps. Citizen integration].

PMID- 24941524
TI  - [Diabsat, diabetes management by satellite].
AB  - The Diabsat programme, coordinated by the Midi-Pyrenees diabetes network
      (Diamip), uses new technologies to enable patients to update the tests for
      chronic complications of their diabetes. In the long run, this favours their
      health prognosis and their quality of life.

PMID- 24941526
TI  - [Epidemiology of physical disabilities in France].
AB  - Neurological pathologies and conditions affecting the musculoskeletal system have
      significant effects on motor skills. Bone and joint disabilities are the most
      common but the most severe disabilities are linked to neurological conditions,
      particularly as they are often associated with cognitive deficits.

PMID- 24941527
TI  - ["Disability is part of humanity's heritage"].
AB  - To support disabled people, it is necessary to change perspectives, to consider
      disability differently and to integrate it into our society as soon as possible.
      The quality of support and that of care are closely linked and interdependent. An
      interview with Pascal Jacob, president of the association Handidactique I = MC2
      and author of a report on this subject presented last June to the French Minister
      for Social Affairs and Health.

PMID- 24941528
TI  - [Disability, for a revolution of thought and action].
AB  - While considerable progress has been made, disabled people are still perceived as
      "separate" beings in our society. For them to be integrated, it is necessary to
      accept their difference and favour their autonomy. The respect of the rights of
      disabled people thereby enables professionals to position themselves within an
      ethical support approach. An interview with Charles Gardou, an anthropologist and
      university professor at Lumiere-Lyon 2 University.

PMID- 24941529
TI  - [Disabilities and vulnerability].
AB  - Disability is characterised by vulnerability. This vulnerability is even greater
      for dependent people. Only compassion enables the person to exercise their
      autonomy.

PMID- 24941530
TI  - [From care to consideration of disabled people].
AB  - The law of 11th February 2005 relating to the equality of the rights and
      opportunities, participation and citizenship of disabled people was a major step
      forward. Nevertheless, more progress is needed to ensure more consideration is
      given to disabled people.

PMID- 24941531
TI  - [Coordinating schooling, care and rehabilitation].
AB  - Close collaboration has been established between a care and rehabilitation centre
      and a regional special needs school. The cooperation and interdisciplinarity of
      the approach ensures young people with motor disabilities are supported
      throughout their schooling, while being provided with the necessary care and
      rehabilitation.

PMID- 24941532
TI  - [Caring for the aging and institutionalized disabled person].
AB  - The French national group of public social and medical-social institutions
      (GEPSO) has for several years been studying the issue of the ageing of disabled
      people. These people need more complex care and can present a loss of autonomy
      requiring changes to their day-to-day life.

PMID- 24941533
TI  - [Supporting disabled people at home].
AB  - More and more disabled people are determined to live in an ordinary home. Home
      nursing care services can work together to ensure the person thrives, if they
      accept the reality of the situation and if the service is able to adapt to the
      person's wishes and needs.

PMID- 24941534
TI  - [Supporting the health of the disabled person].
AB  - In 2013, the French national agency for the assessment and quality of social and
      medical-social institutions and services (ANESM) issued recommendations
      concerningthe support of the health of disabled people. These guidelines
      underline that the training and support of professionals are necessary, as well
      as the participation of the disabled person in their care project.

PMID- 24941535
TI  - [Organizing the care and professional integration of disabled people].
AB  - Carbet general hospital, in Martinique, is devoted to specialised follow-up and
      rehabilitation care in physical and rehabilitation medicine. It also aims to
      facilitate the employment of people with motor disabilities. The patients benefit
      from an early integration approach at the same time as the care and
      rehabilitation, while taking into account the cultural values specific to
      Martinique society.

PMID- 24941536
TI  - [The dependent disabled person, a daily learning experience].

PMID- 24941537
TI  - [Sexuality and the disabled person].

PMID- 24941538
TI  - [Bibliography. Thinking differently about disabilities].

PMID- 24941539
TI  - [Use of mixed approaches in nursing science].
AB  - The epistemological diversity which characterises modern day nursing science
      offers researchers a wide range of methodologies enabling them to explore their
      research themes. Mixed approaches, which combine qualitative and quantitative
      approaches, seem to appeal to a growing number of researchers.

PMID- 24941540
TI  - [The role of the nurse in the use of medical records].

PMID- 24941541
TI  - Choices.

PMID- 24941542
TI  - Divorce and retirement benefits.

PMID- 24941543
TI  - It is time to consider HSA plans.

PMID- 24941544
TI  - Eight lessons from the dental malpractice experience.

PMID- 24941545
TI  - Dentistry and the cloud - is it tome to make the move?

PMID- 24941546
TI  - Virtualization and cloud computing in dentistry.
AB  - The use of virtualization and cloud computing has changed the way we use
      computers. Virtualization is a method of placing software called a hypervisor on
      the hardware of a computer or a host operating system. It allows a guest
      operating system to run on top of the physical computer with a virtual machine
      (i.e., virtual computer). Virtualization allows multiple virtual computers to run
      on top of one physical computer and to share its hardware resources, such as
      printers, scanners, and modems. This increases the efficient use of the computer
      by decreasing costs (e.g., hardware, electricity administration, and management)
      since only one physical computer is needed and running. This virtualization
      platform is the basis for cloud computing. It has expanded into areas of server
      and storage virtualization. One of the commonly used dental storage systems is
      cloud storage. Patient information is encrypted as required by the Health
      Insurance Portability and Accountability Act (HIPAA) and stored on off-site
      private cloud services for a monthly service fee. As computer costs continue to
      increase, so too will the need for more storage and processing power. Virtual and
      cloud computing will be a method for dentists to minimize costs and maximize
      computer efficiency in the near future. This article will provide some useful
      information on current uses of cloud computing.

PMID- 24941547
TI  - Can we recruit underrepresented minorities into the dental profession in
      Massachusetts?

PMID- 24941549
TI  - Ten under 10.

PMID- 24941548
TI  - Systematic implant information tracking.

PMID- 24941550
TI  - Malignant fibrous histiocytoma clinically mimicking dental abscess in a child:
      report of an unusual case.
AB  - Swellings of the orofacial tissues arising from infections of dental origin are
      relatively common. Occasionally a similar presentation may be due to a malignant
      tumor, and oral clinicians must always bear this possibility in mind with facial
      swellings that do not respond to conventional therapy Malignant fibrous
      histiocytoma is a high-grade aggressive sarcoma, which is relatively rare in
      children and uncommon in both the head-and-neck and mandibular regions. This
      article describes an unusual case of malignant fibrous histiocytoma involving the
      mandible of an 11-year-old child. The purpose of this article is to emphasize the
      importance of diagnosing such lesions in the early stage to improve prognosis and
      limit complications.

PMID- 24941551
TI  - Clinician's corner: a clinico-pathologic correlation.

PMID- 24941552
TI  - Granular cell tumor.

PMID- 24941553
TI  - Odontogenic sinusitis: an underdiagnosed condition.

PMID- 24941554
TI  - You fill in the blank--do we still help to give you a wonderful life?

PMID- 24941555
TI  - Spotlight on forensic nursing.

PMID- 24941556
TI  - International day of the midwife.

PMID- 24941557
TI  - Positive outcomes through research explored.

PMID- 24941558
TI  - Celebrating nurses and midwives.

PMID- 24941559
TI  - Moving from a state view to a national perspective.

PMID- 24941560
TI  - Spotlight on forensic nursing.

PMID- 24941561
TI  - Not waving drowning-challenging the documentation arms race in nursing.

PMID- 24941562
TI  - Fake medicines are everybody's business.

PMID- 24941563
TI  - Importance of appropriate interpreters.

PMID- 24941564
TI  - Developing a nurse-led clinic for patients with Parkinson's disease.

PMID- 24941565
TI  - Surviving night shift.

PMID- 24941566
TI  - Limits of the law.

PMID- 24941568
TI  - The nurse who is there when life's easing the clock is five minutes to midnight.

PMID- 24941569
TI  - Building palliative care capacity in rural health: a collaborative approach.

PMID- 24941567
TI  - Using motivational interviewing to encourage women with gestational diabetes
      mellitus to breastfeed as a method of reducing their risk of type 2 diabetes
      mellitus.

PMID- 24941570
TI  - Supporting transitioning towards end of life.

PMID- 24941571
TI  - The role of a nurse practitioner in palliative care.

PMID- 24941572
TI  - Palliative care online learning modules to help source the evidence.

PMID- 24941573
TI  - Investigating place of death preference among cancer patients and their carers.

PMID- 24941574
TI  - Death, dying and reflective practice.

PMID- 24941575
TI  - Bullying needs to stop.

PMID- 24941576
TI  - Tackling antibiotic resistance.

PMID- 24941577
TI  - Waiting for a response.

PMID- 24941578
TI  - Zoe's Law.

PMID- 24941579
TI  - The research requirement.

PMID- 24941581
TI  - Critical thinker: a conversation with health services researcher (interview by
      Carmen Peota).

PMID- 24941580
TI  - Surviving the shortfall: decreased research funding from traditional sources has
      led some investigators to get creative.

PMID- 24941582
TI  - Research savvy: more medical students than ever are engaging in research while in
      school.

PMID- 24941583
TI  - Real-world research: practicing physicians test new guidelines and protocols in
      the settings where they'll be used.

PMID- 24941584
TI  - The virtues of irrelevance: why our opening comments are so important.

PMID- 24941585
TI  - Moving on but not fading away: parting thoughts from longtime legislator Tom
      Huntley.

PMID- 24941586
TI  - The muddling of medicine.

PMID- 24941587
TI  - Synthetic marijuana use and development of catatonia in a 17-year-old male.

PMID- 24941588
TI  - Congenital epulis in a newborn.

PMID- 24941589
TI  - Driveline infection after HeartMate II associated with lower rates of cardiac
      transplantation and increased incidence of sepsis in bridge-to-transplant
      population.

PMID- 24941590
TI  - Rare cause of pancreatitis in a 20-year-old female.

PMID- 24941591
TI  - The ticking heart: a case and review of acute lyme cardiac complications.

PMID- 24941592
TI  - Quantitative analyses of REM sleep without atonia in children and adolescents
      with REM sleep behavior disorder.

PMID- 24941593
TI  - Re-irradiation of the head and neck using highly conformal tomotherapy intensity
      modulated radiation therapy.

PMID- 24941594
TI  - Quantitative assessment of pediatric hand function using touchscreen technology.

PMID- 24941595
TI  - An unusual cause for melena.

PMID- 24941596
TI  - Development of a neuroscience research registry.
AB  - There is little data on the long-term health outcomes of patients with
      neurological conditions treated at long-term acute care specialty hospitals. In
      order to learn more about these patients and the most effective way to care for
      them, Bethesda Hospital in St. Paul created a neuroscience research registry. The
      registry's target population is patients with complex neurological conditions
      such as aneurysm or intracranial bleed, stroke, seizures, delirium and confusion
      and traumatic brain injury. This article describes the development of the
      registry, which has enrolled 857 patients thus far, and what is being learned
      about those patients.

PMID- 24941597
TI  - How you start the conversation matters.
AB  - Immunization rates are one of the many measures of quality care that are of
      interest to physicians. Immunization rates for children younger than 3 years of
      age in Minnesota have held steady between 80% and 90%. One reason they have not
      increased is because of emerging hesitancy among some parents to vaccinate their
      children. This article describes what research has taught us about working with
      vaccine-hesitant parents and how starting a conversation in a way that presumes
      parents will vaccinate may improve the odds of children getting immunized.

PMID- 24941598
TI  - Being called: reflections on becoming a physician.

PMID- 24941599
TI  - Take a note on that: CMIOs help lead physician documentation reform.

PMID- 24941600
TI  - Health information exchange: moving forward or stuck in neutral?

PMID- 24941601
TI  - The triple aim and healthcare IT leaders: time for action.

PMID- 24941602
TI  - Quality improvement piedmont healthcare.

PMID- 24941603
TI  - Incentivizing better health: one hospital institutes the ultimate rewards
      program: a healthier life.

PMID- 24941604
TI  - Making the enabled patient an engaged patient Cleveland Clinic's LORI POSK, M.D.
      shares learnings from her organization's ambitious patient portal initiative.

PMID- 24941605
TI  - Soul road: one solo doc's extensive EMR journey implementing an EMR is a long
      process fraught with obstacles, especially for a solo practitioner.

PMID- 24941606
TI  - Employee population health infrastructure a self-insured health system taps into
      analytics for accountable care.

PMID- 24941607
TI  - Consultant: providers need to look ahead to MU stage 3: expert speaks about
      challenges, strategies, trends concerning MU, while looking to the future.

PMID- 24941608
TI  - Medicaid now driving many state HIE agendas CMS funding for HIE development is
      available if tied to Medicaid needs.

PMID- 24941609
TI  - Candidate pushback. How the tough economy has changed the mindset of the even the
      best job candidates.

PMID- 24941610
TI  - The perils and promises of microbial abundance: novel natures and model
      ecosystems, from artisanal cheese to alien seas.
AB  - Microbial life has been much in the news. From outbreaks of Escherichia coli to
      discussions of the benefits of raw and fermented foods to recent reports of life
      forms capable of living in extreme environments, the modest microbe has become a
      figure for thinking through the presents and possible futures of nature, writ
      large as well as small. Noting that dominant representations of microbial life
      have shifted from an idiom of peril to one of promise, we argue that microbes-
      especially when thriving as microbial communities--are being upheld as model
      ecosystems in a prescriptive sense, as tokens of how organisms and human
      ecological relations with them could, should, or might be. We do so in reference
      to two case studies: the regulatory politics of artisanal cheese and the
      speculative research of astrobiology. To think of and with microbial communities
      as model ecosystems offers a corrective to the scientific determinisms we detect
      in some recent calls to attend to the materiality of scientific objects.

PMID- 24941611
TI  - Hot air ablowin! 'Media-speak', social conflict, and the Australian 'decoupled'
      wind farm controversy.
AB  - In work in science, technology, and society social conflict around wind farms has
      a growing profile, not least because it draws our attention to two key
      interrelated themes: 'science, technology and governance' and 'socio
      technological systems'. In this article on Australian wind farm development and
      siting, these themes are highlighted in contexts of sustainability, legitimacy,
      and competency for policy effectiveness. There is enduring social conflict around
      wind farms at the local community level, but little government understanding of
      this conflict or willingness to respond adequately to resolve it. This article
      examines the conflict through the lens of print media analysis. A key finding of
      the five identified is that people seeing wind farms as spoiling a sense of place
      is a primary cause of enduring social conflict at the local community level
      around wind farms, alongside significant environmental issues and inadequate
      community engagement; this finding also indicates a central reason for the highly
      problematic state of Australian wind energy transitions. In turn, by identifying
      this problematic situation as one of a significantly 'decoupled' and
      'dysfunctional' condition of the Australian socio-technological wind farm
      development and siting system, I suggest remedies including those of a
      deliberative nature that also respond to the Habermas-Mouffe debate. These inform
      a socio-technical siting approach or pathway to better respect and navigate
      contested landscapes for enhanced renewable energy transitions at the local
      level.

PMID- 24941612
TI  - Understanding 'anticipatory governance'.
AB  - Anticipatory governance is 'a broad-based capacity extended through society that
      can act on a variety of inputs to manage emerging knowledge-based technologies
      while such management is still possible'. It motivates activities designed to
      build capacities in foresight, engagement, and integration--as well as through
      their production ensemble. These capacities encourage and support the reflection
      of scientists, engineers, policy makers, and other publics on their roles in new
      technologies. This article reviews the early history of the National
      Nanotechnology Initiative in the United States, and it further explicates
      anticipatory governance through exploring the genealogy of the term and
      addressing a set of critiques found in the literature. These critiques involve
      skepticism of three proximities of anticipatory governance: to its object,
      nanotechnology, which is a relatively indistinct one; to the public, which
      remains almost utterly naive toward nanotechnology; and to technoscience itself,
      which allegedly renders anticipatory governance complicit in its hubris. The
      article concludes that the changing venues and the amplification within them of
      the still, small voices of folks previously excluded from offering constructive
      visions of futures afforded by anticipatory governance may not be complete
      solutions to our woes in governing technology, but they certainly can contribute
      to bending the long arc of technoscience more toward humane ends.

PMID- 24941613
TI  - Working data together: the accountability and reflexivity of digital astronomical
      practice.
AB  - Drawing on ethnomethodology, this article considers the sequential work of
      astronomers who combine observations from telescopes at two observatories in
      making a data set for scientific analyses. By witnessing the induction of a
      graduate student into this work, it aims at revealing the backgrounded
      assumptions that enter it. I find that these researchers achieved a consistent
      data set by engaging diverse evidential contexts as contexts of accountability.
      Employing graphs that visualize data in conventional representational formats of
      observational astronomy, experienced practitioners held each other accountable by
      using an 'implicit cosmology', a shared (but sometimes negotiable)
      characterization of 'what the universe looks like' through these formats. They
      oriented to data as malleable, that is, as containing artifacts of the observing
      situation which are unspecified initially but can be defined and subsequently
      removed. Alternating between reducing data and deducing astronomical phenomena,
      they ascribed artifacts to local observing conditions or computational
      procedures, thus maintaining previously stabilized phenomena reflexively. As
      researchers in data-intensive sciences are often removed from the instruments
      that generated the data they use, this example demonstrates how scientists can
      achieve agreement by engaging stable 'global' data sets and diverse contexts of
      accountability, allowing them to bypass troubling features and limitations of
      data generators.

PMID- 24941614
TI  - Disciplining ethnicity: social sorting intersects with political demography in
      Israel's pre-state period.
AB  - This article presents an analysis of the professional and political activities of
      the demographer Roberto Bachi prior to Israel's establishment as a state in 1948.
      The article describes his involvement in two interconnected major areas: first,
      his advocacy of pro-natal policies, connected to a nation-building strategy by
      the Jewish population to achieve numerical dominance over Arab Palestinians in
      areas to be incorporated in the Jewish state, and second, the development of
      Jewish ethnic distinctions, particularly the 'Mizrahi type', to track differences
      in birthrates and changing cultural features within the Jewish population. The
      article also revises the historical record by showing the importance of this
      ethnic classification in the years prior to the large waves of Jewish immigration
      from Arab countries. Without the reworking of the popular category 'Mizrahi' into
      a scientifically systematized category by a demographer who would become the head
      of the state's Central Bureau of Statistics upon its founding in 1948, this
      binary social epistemology could not be as strong and legitimate as it actually
      was. Two factors account for Bachi's success. First was his ability to provide a
      new way of understanding the present in terms of the future. His numerical
      predictions on the Jewish and Arab demographic development made statistics and
      demography an indispensable technology for public policy and social planning.
      Second was his role as a boundary actor--a unique mediating position between
      political and scientific spheres. The Israeli case study exemplifies similar
      dynamics found in other countries during periods of structuring the modern state,
      namely, processes in which experts of infrastructural knowledge such as
      statistics and demography saw themselves as responsible for the national progress
      and its social modernity.

PMID- 24941615
TI  - Methodology discourses as boundary work in the construction of engineering
      education.
AB  - Engineering education research is a new field that emerged in the social sciences
      over the past 10 years. This analysis of engineering education research
      demonstrates that methodology discourses have played a central role in the
      construction and development of the field of engineering education, and that they
      have done so primarily through boundary work. This article thus contributes to
      science and technology studies literature by examining the role of methodology
      discourses in an emerging social science field. I begin with an overview of
      engineering education research before situating the case within relevant bodies
      of literature on methodology discourses and boundary work. I then identify two
      methodology discourses--rigor and methodological diversity--and discuss how they
      contribute to the construction and development of engineering education research.
      The article concludes with a discussion of how the findings relate to prior
      research on methodology discourses and boundary work and implications for future
      research.

PMID- 24941616
TI  - [License-master-doctorate, 5 years later].

PMID- 24941618
TI  - [New recommendations for hospital discharge from the maternity unit].

PMID- 24941617
TI  - [Ethical questions surrounding the withholding of nutritional support in
      neonatology].

PMID- 24941619
TI  - [Influencing the eating behaviors of young children].

PMID- 24941620
TI  - [The effect of anti-tobacco laws on the reduction of premature birth].

PMID- 24941622
TI  - [Communication with babies in the hospital. Listening to the baby].

PMID- 24941621
TI  - [Care of febrile newborns in the emergency department and hospitalization].

PMID- 24941623
TI  - [Caregiver-newborn interaction and the care relationship].
AB  - The care provided to a newborn is mainly organised around constant paraverbal
      communication, consisting of signs and contact. Among the many methods of non
      verbal communication of the newborn, the expression and touch are essential for
      the caregiver. The methods of communication used by the infant and the messages
      they deliver are interpreted by professionals to give them meaning in order to
      respond as best as possible to the baby's needs.

PMID- 24941624
TI  - [Psychomotor skills and initial bonds in neonatology].
AB  - In neonatology units, the professional approach of the psychomotor therapist
      focuses on the observation of the baby to favour his or her psychomotor
      development. She acts in close cooperation with the medical and nursing teams and
      includes the parents in her work.

PMID- 24941625
TI  - [Favoring the parent-child relationship in neonatal intensive care].
AB  - In neonatal intensive care, premature babies are cared for from birth in a hyper
      medicalised environment, far removed from the normal family environment. To
      favour the initial bond in this specific context, caregivers support parents in
      their discovery of their baby and help them to establish a relationship with him
      or her.

PMID- 24941626
TI  - [Culture in initial interactions].
AB  - Communication between infants and their parents is established through the
      initial interactions which begin at birth. These are unique to each parent-infant
      dyad and are structured both on the basis of the reactions, behaviour and
      characteristics specific to the babies as well as on the images, sensations,
      projections and representations of the parents. Culture and language are
      important elements in this context.

PMID- 24941627
TI  - [Intercultural approach in the care relationship in pediatrics].
AB  - The intercultural approach in paediatrics requires caregivers to consider care as
      a specific approach which takes into account the diversity of ages, pathologies
      or disorders, family environments, education, etc. The professionals integrate
      these factors in order to adapt their support accordingly and favour the
      caregiver-patient relationship.

PMID- 24941628
TI  - [Bibliography. Communication with the baby in the hospital].

PMID- 24941629
TI  - [Mediation model in adolescent psychology].
AB  - Body mediation is today used as a tool for establishing a relationship with a
      young person experiencing psychological suffering. It is particularly useful in
      adolescence, a period marked by the destabilisation of emotional and relational
      fields.

PMID- 24941630
TI  - [Situation analysis in the training of child health nurses].
AB  - Situation analysis has been used as a pedagogical tool in child health nurse
      training for some thirty years. An analysis of the work of trainers overseeing
      students' work placements highlight the need to consider in detail the definition
      of the terms "situation" and "professional situation". Reviewing what is often
      considered as obvious in this way helps to improve learning.

PMID- 24941631
TI  - [Choosing the name in international adoption].
AB  - In the context of international adoption, the question is raised of the links
      which the adoptive parents may or may not maintain with the culture of the
      child's birth country. The name which the adoptive parents choose reflects this
      questioning. A study was carried out into this subject with parents and children
      in order to gain a better understanding of the feelings of belonging, filiation
      and affiliation in these situations.

PMID- 24941632
TI  - AIDS and cancer.

PMID- 24941633
TI  - Resilience and response to hazards and threats, everybody's business.

PMID- 24941634
TI  - An epidemiological perspective on the causes of breast cancer.

PMID- 24941635
TI  - Will we ever be able to afford good cancer care?

PMID- 24941636
TI  - Submarine engineering across the years.

PMID- 24941637
TI  - How to live forever.

PMID- 24941639
TI  - Case history diagnosis, treatment and care plan for the national health service
      in England in 2011.

PMID- 24941638
TI  - Windsor Castle.

PMID- 24941641
TI  - Sex--is this the most dangerous human activity for all life on Earth.

PMID- 24941640
TI  - The Lettsomain Lecture. With Scott in the Antarctic Edward Wilson, explorer.
      Naturalist, artist.

PMID- 24941642
TI  - Defence in the twenty-first century.

PMID- 24941643
TI  - Neurologists and neuro-oncology.

PMID- 24941644
TI  - The evolution of brain tumour surgery.

PMID- 24941645
TI  - Neurosurgery of adult brain tumours.

PMID- 24941647
TI  - Cell biology of brain tumours--resistance sensitivity.

PMID- 24941646
TI  - Neurosurgery of paediatric brain tumours.

PMID- 24941648
TI  - Brain tumour manifesto--brain tumour charities.

PMID- 24941649
TI  - Brain tumour manifesto--brain tumour charities.

PMID- 24941650
TI  - Neuropathology of brain tumours from experimental concepts to applied diagnosis.

PMID- 24941651
TI  - There is beauty in all around I see.

PMID- 24941652
TI  - A matter of life and death: conversations with pathologists.

PMID- 24941653
TI  - Expectations, economics and healthcare.

PMID- 24941654
TI  - Ethical issues in end of life care.

PMID- 24941655
TI  - Maritime logistics.

PMID- 24941657
TI  - Can stem cells repair the brain.

PMID- 24941656
TI  - Will the UK NHS organisations deliver electronic care records systems by
      2015/2016? - a debate.

PMID- 24941658
TI  - The longbow.

PMID- 24941659
TI  - Medicine, science and philanthrophy: Fothergill, Lettsom, Priestly, Franklin and
      their circle.

PMID- 24941660
TI  - The secret history of Georgian Kensington Palace.

PMID- 24941661
TI  - Thomas is the best healer of the virtuous sick: the medical miracles of Thomas of
      Canterbury.

PMID- 24941662
TI  - Preface. Capsaicin as a therapeutic molecule.

PMID- 24941663
TI  - Capsaicin and sensory neurones: a historical perspective.
AB  - Capsaicin, the pungent ingredient of red pepper has become not only a "hot" topic
      in neuroscience but its new target-related unique actions have opened the door
      for the drug industry to introduce a new chapter of analgesics. After several
      lines of translational efforts with over 1,000 patents and clinical trials, the
      8% capsaicin dermal patch reached the market and its long-lasting local analgesic
      effect in some severe neuropathic pain states is now well established. This
      introductory chapter outlines on one hand the historical background based on the
      author's 50 years of experience in this field and on the other hand emphasizes
      new scopes, fascinating perspectives in pharmaco-physiology, and molecular
      pharmacology of nociceptive sensory neurons. Evidence for the effect of capsaicin
      on C-polymodal nociceptors (CMH), C-mechanoinsensitive (CHMi), and silent C
      nociceptors are listed and the features of the capsaicin-induced blocking effects
      of nociceptors are demonstrated. Common and different characteristics of
      nociceptor-blocking actions after systemic, perineural, local, intrathecal, and
      in vitro treatments are summarized. Evidence for the misleading conclusions drawn
      from neonatal capsaicin pretreatment is presented. Perspectives opened from
      cloning the capsaicin receptor "Transient Receptor Potential Vanilloid 1" (TRPV1)
      are outlined and potential molecular mechanisms behind the long-lasting
      functional, ultrastructural, and nerve terminal-damaging effects of capsaicin and
      other TRPV1 agonists are summarized. Neurogenic inflammation and the long-list of
      "capsaicin-sensitive" tissue responses are mediated by an unorthodox dual sensory
      efferent function of peptidergic TRPV1-expressing nerve terminals which differ
      from the classical efferent and sensory nerve endings that have a unidirectional
      role in neuroregulation. Thermoregulatory effects of capsaicin are discussed in
      detail. It is suggested that since hyperthermia and burn risk due to enhanced
      noxious heat threshold are the major obstacles of some TRPV1 antagonists, they
      could be overcome. The special "multisteric" gating function of the TRPV1 cation
      channel provides the structural ground for blocking chemical activation of TRPV1
      without affecting its responsiveness to physical stimuli. A new chapter of
      potential analgesics targeting nociceptors is now already supported for pain
      relief in persistent pathological pain states.

PMID- 24941664
TI  - Pharmacology of the capsaicin receptor, transient receptor potential vanilloid
      type-1 ion channel.
AB  - The capsaicin receptor, transient receptor potential vanilloid type 1 ion channel
      (TRPV1), has been identified as a polymodal transducer molecule on a sub-set of
      primary sensory neurons which responds to various stimuli including noxious heat
      (> -42 degrees C), protons and vanilloids such as capsaicin, the hot ingredient
      of chilli peppers. Subsequently, TRPV1 has been found indispensable for the
      development of burning pain and reflex hyperactivity associated with inflammation
      of peripheral tissues and viscera, respectively. Therefore, TRPV1 is regarded as
      a major target for the development of novel agents for the control of pain and
      visceral hyperreflexia in inflammatory conditions. Initial efforts to introduce
      agents acting on TRPV1 into clinics have been hampered by unexpected side-effects
      due to wider than expected expression in various tissues, as well as by the
      complex pharmacology, of TRPV1. However, it is believed that better understanding
      of the pharmacological properties of TRPV1 and specific targeting of tissues may
      eventually lead to the development of clinically useful agents. In order to
      assist better understanding of TRPV1 pharmacology, here we are giving a
      comprehensive account on the activation and inactivation mechanisms and the
      structure-function relationship of TRPV1.

PMID- 24941665
TI  - TRPV1 in the central nervous system: synaptic plasticity, function, and
      pharmacological implications.
AB  - The function of TRPV1 in the peripheral nervous system is increasingly being
      investigated for its anti-inflammatory and antinociceptive properties in an
      effort to find a novel target to fight pain that is nonaddictive. However, in
      recent years, it was discovered that TRPV1 is also associated with a wide array
      of functions and behaviors in the central nervous system, such as fear, anxiety,
      stress, thermoregulation, pain, and, more recently, synaptic plasticity, the
      cellular mechanism that allows the brain to adapt to its environment. This
      suggests a new role for brain TRPV1 in areas such as learning and memory, reward
      and addiction, and development. This wide array of functional aspects of TRPV1 in
      the central nervous system (CNS) is in part due to its multimodal form of
      activation and highlights the potential pharmacological implications of TRPV1 in
      the brain. As humans also express a TRPV1 homologue, it is likely that animal
      research will be translational to humans and therefore worthy of exploration.
      This review outlines the basic expression patterns of TRPV1 in the CNS along with
      what is known regarding its signaling mechanisms and its role in the
      aforementioned brain functions. As TRPV1 involvement in synaptic plasticity has
      never been fully reviewed elsewhere, it will be a focus of this review. The
      chapter concludes with some of the potential pharmaceutical implications of
      further TRPV1 research.

PMID- 24941666
TI  - Topical capsaicin formulations in the management of neuropathic pain.
AB  - This chapter reviews the scientific and clinical evidence supporting the use of
      topical formulations containing the pungent principle of chili peppers-
      capsaicin, for the treatment of peripheral neuropathic pain. Given the
      limitations of current oral and parenteral therapies for the management of pain
      arising from various forms of nerve injury, alternate therapeutic approaches that
      are not associated with systemic adverse events that limit quality of life,
      impair function, or threaten respiratory depression are critically needed.
      Moreover, neuropathic conditions can be complicated by progressive changes in the
      central and peripheral nervous system, leading to persistent reorganization of
      pain pathways and chronic neuropathic pain. Recent advances in the use of high
      dose topical capsaicin preparations hold promise in managing a wide range of
      painful conditions associated with peripheral neuropathies and may in fact help
      reduce suffering by reversing progressive changes in the nervous system
      associated with chronic neuropathic pain conditions.

PMID- 24941667
TI  - Capsaicin-based therapies for pain control.
AB  - The TRPV1 receptor is known to play a role in nociceptive transmission in
      multiple organ systems, usually in response to the pain of inflammation. TRPV1
      antagonism has so far shown limited benefit in antinociception. Capsaicin, a
      TRPV1 agonist, has been shown to induce a refractory period in the nerve terminal
      expressing TRPV1 and even, in sufficient dosing, to create long-term nerve
      terminal defunctionalization. This has led to research into topical capsaicin as
      a treatment for multiple painful conditions. The majority of work has focused on
      musculoskeletal pain and neuropathic pain and has revealed that although low-dose
      topical capsaicin has limited effectiveness as an analgesic, high-dose capsaicin,
      when tolerated, has the potential for long-term analgesia in certain types of
      neuropathic pain.

PMID- 24941668
TI  - Intranasal capsaicin in management of nonallergic (vasomotor) rhinitis.
AB  - Capsaicin is a selective transient receptor potential vanilloid 1 (TRPV1) ion
      channel agonist and has been demonstrated to reduce nerve conduction of
      nociceptive C fibers in the trigeminal nerve without affecting conduction in
      Adelta fibers. This chapter reviews the classification of chronic rhinitis
      subtypes, the prevalence and epidemiology of nonallergic rhinitis (NAR),
      postulated pathophysiology and mechanisms of NAR including the role of transient
      receptor potential (TRP) ion channels and discusses the potential therapeutic
      benefits of capsaicin in the treatment of chronic rhinitis subtypes, specifically
      NAR. Evidence supports that hypersensitivity of TRP ion channels on sensory
      afferent neurons innervating nasal mucosa is responsible for inducing NAR
      symptoms. These symptoms, characterized as excessive nasal glandular secretion,
      nasal congestion, and headache, are mediated through neuropeptide release during
      axonal and parasympathetic reflexes which are initiated by a spectrum of
      nonspecific irritants that activate TRP channels. Rational approaches to treat
      the pathophysiology of NAR would be to develop therapies with selective TRPV1
      agonist activity like capsaicin that target desensitization of TRP ion channels
      on sensory afferent nerves.

PMID- 24941669
TI  - Capsaicin as an anti-obesity drug.
AB  - Laboratory studies support a role of capsaicin as an anti-obesity agent.
      Intestinal mucosal afferent nerves appear to play a role in controlling adipose
      tissue distribution between visceral and subcutaneous sites. Activation of the
      transient receptor potential vanilloid-1 channels by capsaicin prevents
      adipogenesis. A neurogenic mechanism modulates the regulation of fat metabolism
      by transient receptor potential vanilloid-1-sensitive sensory nerves. A neural
      pathway enables the selective activation of the central network that regulates
      brown adipose tissue sympathetic nerve activity in response to a specific
      stimulation of gastrointestinal transient receptor potential channels. Dietary
      capsaicin reduces metabolic dysregulation in obese/diabetic mice by enhancing
      expression of adiponectin and its receptor. The effects of capsaicin in adipose
      tissue and liver are related to its dual action on peroxisome proliferator
      activated receptor alpha and transient receptor potential vanilloid-1
      expression/activation. Local desensitization of the abdominal capsaicin-sensitive
      fibers attenuates the hypometabolic adaptation to food deprivation. Truncal
      vagotomy leads to significant reductions in both diet-induced weight gain and
      visceral abdominal fat deposition. Vagal de-afferentation leads to a more modest,
      but clinically and statistically significant, reduction in visceral abdominal
      fat. Thermogenesis and lipid metabolism-related proteins are altered upon
      capsaicin treatment in white adipose tissue. Capsaicin induces apoptosis and
      inhibits adipogenesis in preadipocytes and adipocytes. Epidemiologic data show
      that consumption of foods containing capsaicin is associated with a lower
      prevalence of obesity. Clinical evidence supports a role of capsaicin as an anti
      obesity agent. Both oral and gastrointestinal exposure to capsaicin increase
      satiety and reduce energy and fat intake; the stronger reduction with oral
      exposure suggests a sensory effect of capsaicin. Bioactive components containing
      capsaicin may support weight maintenance after a hypocaloric diet. Capsaicin
      consumption 1 h before low intensity exercise is a valuable supplement for the
      treatment of individuals with hyperlipidemia and/or obesity because it improves
      lipolysis. Capsinoid ingestion increases energy expenditure through the
      activation of brown adipose tissue in humans. Capsinoid ingestion is associated
      with an increase in fat oxidation that is nearly significant; and two common
      genetic variants may be predictors of response. Further clinical research to
      develop convenient approaches for obese individuals to take advantage of this
      common dietary ingredient to prevent the onset or curtail the progression of
      obesity will be instructive and clinically relevant.

PMID- 24941670
TI  - The potential antitumor effects of capsaicin.
AB  - Capsaicin, one of the major pungent ingredients found in red peppers, has been
      recently demonstrated to induce apoptosis in many types of malignant cell lines
      including colon adenocarcinoma, pancreatic cancer, hepatocellular carcinoma,
      prostate cancer, breast cancer, and many others. The mechanism whereby capsaicin
      induces apoptosis in cancer cells is not completely elucidated but involves
      intracellular calcium increase, reactive oxygen species generation, disruption of
      mitochondrial membrane transition potential, and activation of transcription
      factors such as NFkappaB and STATS. Recently, a role for the AMP-dependent kinase
      (AMPK) and autophagy pathways in capsaicin-triggered cell death has been
      proposed. In addition, capsaicin shows antitumor activity in vivo by reducing the
      growth of many tumors induced in mice. In this chapter, we report the last
      advances performed in the antitumor activity of capsaicin and review the main
      signaling pathways involved.

PMID- 24941671
TI  - Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or
      in combination with nonsteroidal anti-inflammatory drugs in healthy human
      subjects and in patients.
AB  - BACKGROUND: Capsaicin is a specific compound acting on capsaicin-sensitive
      afferent nerves. AIM: Capsaicin was used to study the different events of human
      gastrointestinal physiology, pathology, and clinical pharmacology, and possible
      therapeutic approaches to enhance gastrointestinal mucosal defense in healthy
      human subjects and in patients with various different gastrointestinal disorders
      as well as its use with nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy
      subjects and in patients. MATERIALS AND METHODS: The observations were carried
      out in 198 healthy human subjects and in 178 patients with different
      gastrointestinal (GI) diseases (gastritis, erosions, ulcer, polyps, cancer,
      inflammatory bowel diseases, colorectal polyps, cancers), and in 69 patients with
      chronic (Helicobacter pylori positive and negative) gastritis (before and after
      eradication treatment). The gastric secretory responses and their chemical
      composition, gastric emptying, sugar loading test, gastric transmucosal potential
      difference (GTPD) with application of capsaicin alone, after ethanol alone and
      with capsaicin, indomethacin-induced gastric mucosal microbleeding without and
      with capsaicin were studied. The immunohistochemical examinations of the
      capsaicin receptor (TRVP1), calcitonin gene- related peptide (CGRP), and
      substance P (SP) were carried out in gastrointestinal tract, and especially in
      patients with chronic gastritis (with and without Helicobacter infection, before
      and after classical eradication treatment). Classical molecular pharmacological
      methods were applied to study the drugs inhibiting the gastric basal acid output.
      RESULTS: Capsaicin decreased the gastric basal output, enhanced the "non
      parietal" (buffering) component of gastric secretory responses, and gastric
      emptying, and the release of glucagon. Capsaicin prevented the indomethacin- and
      ethanol-induced gastric mucosal damage; meanwhile capsaicin itself enhanced
      (GTPD). Capsaicin prevented the indomethacin-induced gastric mucosal
      microbleeding. The expression of TRVP1 and CGRP increased in the gastric mucosa
      of patients with chronic gastritis (independently of the presence of Helicobacter
      pylori infection), and the successfully carried out eradication treatment. The
      human first phase examinations (the application of acetylsalicylic acid (ASA),
      diclqfenac, and naproxen together with capcaicinoids) (given in doses that
      stimulate capsaicin-sensitive afferent vagal nerves) showed no change in the
      pharmacokinetic parameters of ASA and diclofenac and the ASA and diclofenac
      induced platelet aggregation. CONCLUSIONS: Capsaicin represents a new orally
      applicable gastroprotective agent in healthy human subjects and in patients with
      different chemical and Helicobacter pylori-induced mucosal damage and in many
      other diseases requiring treatment with NSAIDs.

PMID- 24941672
TI  - Capsaicin receptor as target of calcitonin gene-related peptide in the gut.
AB  - Calcitonin gene-related peptide (CGRP), a 37 aminoacid-residue peptide, is a
      marker of afferent fibers in the upper gastrointestinal tract, being almost
      completely depleted following treatment with the selective neurotoxin capsaicin
      that targets these fibers via transient receptor potential vanilloid type-1 (TRPV
      1). It is widely distributed in the peripheral nervous system of mammals where it
      is present as alpha isoform, while intrinsic neurons of the enteric nervous
      systems express predominantly CGRP-beta. Many gastrointestinal functions involve
      CGRP-containing afferent fibers of the enteric nervous system such as defense
      against irritants, intestinal nociception, modulation of gastrointestinal
      motility and secretion, and healing of gastric ulcers. The main effects on
      stomach homeostasis rely on local vasodilator actions during increased acid-back
      diffusion. In humans, release of CGRP through the activation of TRPV-1 has been
      shown to protect from gastric damage induced by several stimuli and to be
      involved in gastritis. In both dyspepsia and irritable bowel syndrome the
      repeated stimulation of TRPV-1 induced an improvement in epigastric pain of these
      patients. The TRPV-1/CGRP pathway might be a novel target for therapeutics in
      gastric mucosal injury and visceral sensitivity.

PMID- 24941673
TI  - Capsaicin for osteoarthritis pain.
AB  - Capsaicin appears to be effective for osteoarthritis pain but it is uncertain
      whether the effect has a dose response, is consistent across joints, or changes
      over time. METHODS: Randomized controlled trials of topical capsaicin use in OA
      were identified from PubMed, EMBASE, and ISI Web of Knowledge. Effect on pain
      scores, patient global evaluation of treatment effectiveness and application site
      burning were assessed by standardised mean differences (SMD), using RevMan.
      RESULTS: Five double-blind randomized controlled trials and one case-crossover
      trial of topical capsaicin use were identified. Formulations ranged from 0.025 to
      0.075%, and trial durations from 4 to 12 weeks. Trials assessed OA of the knee (n
      = 3), hand (n = 1), and a mix of joints (n = 2). Capsaicin treatment efficacy
      (vs. placebo) for change in VAS pain score was moderate, at 0.44 (95% CI 0.25
      0.62) over 4 weeks of treatment. There was no heterogeneity between studies,
      indicating no between-study differences, including effect of OA site or treatment
      concentration. Two studies reported treatment beyond 4 weeks, with divergent
      results. One study reported an effect size of -9 mm after 12 weeks, and maximal
      between-group differences at 4 weeks. A second study reported that between-group
      differences increased over time, up to 20 weeks. Capsaicin was reported as being
      safe and well-tolerated, with no systemic toxicity. Mild application site burning
      affected 35-100% of capsaicin-treated patients with a risk ratio of 4.22 (95% CI
      3.25-5.48, n = 5 trials); incidence peaked in week 1, with incidence rates
      declining over time. CONCLUSIONS: Topical capsaicin treatment four times daily is
      moderately effective in reducing pain intensity up to 20 weeks regardless of site
      of application and dose in patients with at least moderate pain and clinical or
      radiologically defined OA, and is well tolerated.

PMID- 24941674
TI  - The role of capsaicin in dermatology.
AB  - Neurogenic pain and pruritus are the common chief complaints at dermatology
      office visits. Unfortunately, they are also notoriously difficult conditions to
      treat. Topical capsaicin used as a single therapy or as an adjuvant offers a low
      risk option for patients who do not achieve control on other therapies. This
      chapter presents the evidence behind topical capsaicin use in dermatologic
      conditions characterized by neurogenic pain or pruritus, including postherpetic
      neuralgia, notalgia paresthetica, brachioradial pruritus, lichen simplex
      chronicus, prurigo nodularis, pruritus ani, pruritus of hemodialysis, aquagenic
      pruritus, apocrine chromhidrosis, lipodermatosclerosis, alopecia areata, and
      psoriasis. It presents the most common capsaicin formulations, dosages, and
      durations of treatment for each condition. Additionally, the chapter addresses
      various adverse effects and limitations in the use of topical capsaicin in
      dermatology.

PMID- 24941675
TI  - Use of vanilloids in urologic disorders.
AB  - The bladder is an organ rich in vanilloid targets: dense unmyelinated c-fibers
      partially responsible for bladder sensation and response to noxious stimuli.
      Drugs such as capsaicin and resiniferatoxin (RTX) interact with the VR1 vanilloid
      receptor subtype to initially excite then subsequently desensitize the c-fibers.
      This chapter examines the literature describing the use of vanilloid receptor
      agonists in the treatment of the following urological disorders: neurogenic
      bladder (NGB), overactive bladder (OAB), and interstitial cystitis/painful
      bladder syndrome (IC/PBS). Review of the literature was performed using Pubmed
      and the following key words "capsaicin," "resiniferatoxin (RTX)," and "neurogenic
      bladder," "overactive bladder (OAB)," and "interstitial cystitis," "painful
      bladder syndrome." Articles focusing on randomized trials comparing intravesical
      administration of a vanilloid receptor agonist to placebo and those in English
      were reviewed. We conclude that capsaicin and RTX do appear to provide some
      acceptable treatment results in patients with neurogenic bladder, though larger
      studies are needed to confirm this. Although efficacy has been shown in some
      studies, currently the use of vanilloids cannot be recommended for routine use in
      patients with OAB as the need for catheterization may cause the risk to outweigh
      the benefit of treatment. Similarly, for the treatment of BPS, vanilloid receptor
      agonists lack strong evidence for efficacy or tolerability; larger studies are
      needed to define their role. Understanding how vanilloids are able to impact
      these disorders, however, may help further elucidate their underlying
      pathophysiological processes.

PMID- 24941676
TI  - [Together, towards precise oncology!].

PMID- 24941678
TI  - [Multikinase inhibitor regorafenib offers an efficient therapeutic alternative].

PMID- 24941677
TI  - [Endocrine therapy resistance in metastatic breast cancer: mechanisms and
      clinical implications].
AB  - Endocrine therapy remains a mainstay in the treatment of hormone-sensitive
      metastatic breast cancer. Nevertheless, acquired resistance to endocrine therapy
      is an important clinical problem. Understanding the mechanisms of resistance is
      fundamental in order to develop new therapeutic strategies such as mTOR
      inhibition through everolimus. Its efficacy in association with endocrine therapy
      has been shown in two randomized trials. However, the addition of everolimus to
      endocrine therapy is accompanied by a significant increase in potentially severe
      side effects. Identifying and adequately addressing these side effects is crucial
      to decrease toxicity of these new therapies.

PMID- 24941679
TI  - [Stivarga shows effectiveness in practice].

PMID- 24941680
TI  - [Postoperative radiation therapy in lung carcinom].
AB  - Locally advanced non-small-cell lung carcinoma (NSCLC) is a very heterogeous
      disease, the role of postoperative radiation therapy (PORT) in pN2 patients with
      completly resected NSCLC remains controversial. Although an improvment in local
      control has been described in several studies, the effect on survival has been
      contradictory or inconclusive. Retrospective evaluation suggest a positive effect
      of PORT in high risk patients with pN2 disease: RI-resected NSCLC, bulky and
      multilevel N2. However further evaluation of PORT in prospectively randomized
      studies in completely resected pN2 NSCLC is needed.

PMID- 24941681
TI  - [New data confirm it: Zaltrap prolongs survival of all sub-populations with
      metastatic colorectal cancer ].

PMID- 24941682
TI  - [Early gastric cancer: epidemiology, diagnostic and management].
AB  - Stomach cancers are diagnosed at an early stage in less than 10% of cases in
      Europe. They are superficial tumours, involving the mucosa and the submucosa
      only. Node involvement is the most important prognostic factor for these tumours.
      To determine the optimal therapeutic strategy, it is necessary to carry out a
      precise work-up involving an endoscopy, with chemical or virtual colorations and
      an echo-endoscopy. Gastric surgery is the reference treatment. Nowadays,
      endoscopic tumour resection is a validated curative alternative. High quality
      medical expertise is needed for those tumours with a good prognosis, after
      evaluating risk for node involvement, and should be followed by Helicobacter
      pylori eradication and regular endoscopic surveillance.

PMID- 24941683
TI  - [Interventional radiology procedures for malignancies of the liver: ablation
      procedures].
AB  - Percutaneous ablative procedures allow curative treatment of stage BCLC 0 or BCLC
      A hepatocellular carcinoma, as well as liver metastases of colorectal cancer.
      Several methods exist including radiofrequency ablation, the most commonly used.
      These techniques can be used in combination with surgical excision or alone if
      surgery is contraindicated. They are associated with significantly reduced
      mortality as compared to surgery.

PMID- 24941684
TI  - [Cancer patients benefit from analgesic treatment with TARGIN].

PMID- 24941685
TI  - [Therapeutic success with TARGIN in practice].

PMID- 24941686
TI  - [Interventional radiology procedures for malignancies of the liver treatment:
      Intraarterial procedures].
AB  - Intraarterial procedures such as chemoembolization and radioembolization aim for
      the palliative treatment of advanced hepatocellular carcinoma (stage BCLC B and C
      with tumoral portal thrombosis). The combination of hepatic intraarterial
      chemotherapy and systemic chemotherapy can increase the probability of curing
      colorectal cancer with hepatic metastases not immediately accessible to surgical
      treatment or percutaneous ablation.

PMID- 24941687
TI  - [The Onco-hematology clinical research unit at the Geneva University Hospital:
      example of a fruitful public-private partners].
AB  - A better understanding of the molecular deregulation leading to carcinogenesis
      allows the development of numerous novel targeted therapeutic candidates.
      Clinical research in oncology is a critical step to evaluate in a thorough manner
      the safety and efficacy of these innovative compounds. During the last four years
      the fruitful partnership between the Geneva University Hospitals and the Dr.
      Henri Dubois-Ferriere Dinu Lipatti Foundation lead to a dedicated clinical
      research unit for cancer patients with a staff of ten people. Since 2010, more
      than 300 patients were enrolled in more than 70 distinct clinical trials
      evaluating novel therapies for both solid tumors and hematologic malignancies.
      Interestingly, classical cytostatic drugs now represent only a small fraction of
      the new anti-cancer therapies in the pipeline.

PMID- 24941688
TI  - [Quality improvement initiatives in hospitals: which one to choose].
AB  - The number of quality improvement initiatives in hospitals has been steadily
      increasing in the last decades. Most of these initiatives are inspired by three
      quality control and improvement models developed in the manufacturing industry:
      the final inspection, the quality assurance and the total quality management. The
      purpose of this review is to describe how these methods have been implemented in
      healthcare organizations and to assess their effectiveness and acceptability by
      healthcare professionals. This review should help quality managers and healthcare
      professionals to choose a model that is best adapted to their needs and expected
      goals.

PMID- 24941689
TI  - [Factors influencing the return to work after transplantation in 61 renal or
      liver recipient].
AB  - The rate of return to work after transplantation is generally low, however this
      improves the quality of life of recipients. The aim of our study was to
      investigate the low rate after transplantation in 61 renal or liver patients
      followed at the Transplant Center (CTO) of the CHUV in Lausanne, and to analyse
      the occupational, individual and medical factors which may influence it. 39% of
      recipients returned to work after transplantation. The factors <being active pre
      transplant), <with diploma> and <age <45 years olds were significantly related to
      return to work. In conclusion, knowledge of the factors influencing return to
      work after transplantation are important for medical practice, in order to
      propose early medico-socio-professional measures in order to maintain
      workability.

PMID- 24941690
TI  - [Epigenetics and transmission].

PMID- 24941691
TI  - [Middle-East coronavirus: new menace; questions about dromedary].

PMID- 24941692
TI  - [Who am I?].

PMID- 24941694
TI  - [Philippe X, alcoholic and Gerard Depardieu, who is not one].

PMID- 24941693
TI  - [DNA will never be the same: time for enhanced life].

PMID- 24941695
TI  - [Alain Berset proposes to create a center for quality of health care].

PMID- 24941696
TI  - [SSMI wants to decrease unnecessary exams].

PMID- 24941697
TI  - [Quality, a multiple-edges sword].

PMID- 24941698
TI  - Particulate matter sources on an hourly timescale in a rural community during the
      winter.
AB  - Particulate matter (PM) sources at four different monitoring sites in Alexandra,
      New Zealand, were investigated on an hourly timescale. Three of the sites were
      located on a horizontal transect, upwind, central, and downwind of the general
      katabatic flow pathway. The fourth monitoring site was located at the central
      site, but at a height of 26 m, using a knuckleboom, when wind conditions
      permitted. Average hourly PM10 (PM with an aerodynamic diameter < 10 microm)
      concentrations in Alexandra showed slightly different diurnal profiles depending
      on the sampling site location. Each location did, however feature a large evening
      peak and smaller morning peak in PM10 concentrations. The central site in
      Alexandra experienced the highest PM10 concentrations as a result of PM transport
      along a number of katabatic flow pathways. A significant difference in PM10
      concentrations between the central and elevated sites indicated that a shallow
      inversion layer formed below the elevated site, limiting the vertical dispersion
      of pollutants. Four PM10 sources were identified at each of the sites: biomass
      combustion, vehicles, crustal matter, and marine aerosol. Biomass combustion was
      identified as the most significant source of PM10, contributing up to 91% of the
      measured PM10. Plots of the average hourly source contributions to each site
      revealed that biomass combustion was responsible for both the evening and morning
      peaks in PM10 concentrations observed at each of the sites, suggesting that
      Alexandra residents were relighting their fires when they rose in the morning.
      The identification of PM sources on an hourly timescale can have significant
      implications for air quality management. IMPLICATIONS: Monitoring the sources of
      PM10 on an hourly timescale at multiple sites within an airshed provides
      extremely useful information for air quality management. Sources responsible for
      observed peaks in measured diurnal PM10 concentration profiles can be easily
      identified and targeted for reduction. Also, hourly PM10 sampling can provide
      crucial information on the role meteorology plays in the development of elevated
      PM10 concentrations.

PMID- 24941699
TI  - PM2.5 concentrations in London for 2008--a modeling analysis of contributions
      from road traffic.
AB  - We report on the analysis of contributions from road traffic emissions to fine
      particulate matter (PM2.5) concentrations within London for 2008 with the OSCAR
      Air Quality Assessment System. A spatiotemporal evaluation of the OSCAR system
      has been conducted with measurements from the London air quality network (LAQN).
      For the predicted and measured hourly time series of concentrations at 18 sites
      in London, the medians of correlation, mean absolute error, index of agreement,
      and factor of two (FAC2) of all stations were 0.80, 4.1 microg/m3, 0.86, and 74%,
      respectively. Spatial evaluation of modeled and observed annual mean
      concentrations also showed a fairly good agreement, with all the values falling
      within the FAC2 range. According to model predictions, the urban increment
      (including the contributions from urban traffic and other urban sources) was
      evaluated to be on the average 18%, 33%, 39%, and 43% of the total PM2.5 in
      suburban environments, in the urban background, near roads, and near busy roads,
      respectively. However, the highest values of the urban traffic increment can be
      around 50% of the total PM2.5 concentrations near motorways and major roads. The
      total concentrations (including regional background, and the contributions from
      urban traffic and other urban sources) can therefore be almost three times the
      regional background. The total urban increment close to busy roads was around 7-8
      microg/m3, in which the estimated traffic contribution is more than 2 microg/m3.
      On the average, urban traffic contributes approximately 1 microg/m3 of PM2.5 to
      the urban background across London. According to modeling, approximately two
      thirds of the traffic increment originated from exhaust emissions and most of the
      rest was due to brake and tire wear. IMPLICATIONS: The urban increment and
      traffic contribution to the total PM2.5 are significant and spatially
      heterogeneous across London. The highly heterogeneous distribution of PM2.5 hence
      requires detailed modeling studies to be carried out at high spatial resolution,
      which can be particularly important for exposure and health impact assessment.
      This type of information can be used to quantify health impacts resulting from
      specific sources of PM2.5 such as traffic emissions, to aid city and national
      decision makers when formulating pollution control strategies.

PMID- 24941700
TI  - Analysis of atmospheric aerosol (PM2.5) in Recife city, Brazil.
AB  - Several studies indicate that mortality and morbidity can be well correlated to
      atmospheric aerosol concentrations with aerodynamic diameter less than 2.5 microm
      (PM2.5). In this work the PM2.5 at Recife city was analyzed as part of a main
      research project (INAIRA) to evaluate the air pollution impact on human health in
      six Brazilian metropolitan areas. The average concentration, for 309 samples (24
      hr), from June 2007 to July 2008, was 7.3 microg/m3, with an average of 1.1
      microg/m3 of black carbon. The elemental concentrations of samples were obtained
      by x-ray fluorescence. The concentrations were then used for characterizing the
      aerosol, and also were employed for receptor modelling to identify the major
      local sources of PM2.5. Positive matrix factorization analysis indicated six main
      factors, with four being associated to soil dust, vehicles and sea spray,
      metallurgical activities, and biomass burning, while for a chlorine factor, and
      others related to S, Ca, Br, and Na, we could make no specific source
      association. Principal component analysis also indicated six dominant factors,
      with some specific characteristics. Four factors were associated to soil dust,
      vehicles, biomass burning, and sea spray, while for the two others, a chlorine-
      and copper-related factor and a nickel-related factor, it was not possible to do
      a specific source association. The association of the factors to the likely
      sources was possible thanks to meteorological analysis and sources information.
      Each model, although giving similar results, showed factors' peculiarities,
      especially for source apportionment. The observed PM2.5 concentration levels were
      acceptable, notwithstanding the high urbanization of the metropolitan area,
      probably due to favorable conditions for air pollution dispersion. More than a
      valuable historical register these results should be very important for the next
      analysis, which will correlate health data, PM2.5 levels, and sources
      contributions in the context of the six studied Brazilian metropolises.

PMID- 24941701
TI  - Particulate matter speciation profiles for light-duty gasoline vehicles in the
      United States.
AB  - Representative profiles for particulate matter particles less than or equal to
      2.5 microm (PM2.5) are developed from the Kansas City Light-Duty Vehicle
      Emissions Study for use in the US. Environmental Protection Agency (EPA) vehicle
      emission model, the Motor Vehicle Emission Simulator (MOVES), and for inclusion
      in the EPA SPECIATE database for speciation profiles. The profiles are compatible
      with the inputs of current photochemical air quality models, including the
      Community Multiscale Air Quality Aerosol Module Version 6 (AE6). The composition
      of light-duty gasoline PM2.5 emissions differs significantly between cold start
      and hot stabilized running emissions, and between older and newer vehicles,
      reflecting both impacts of aging/deterioration and changes in vehicle technology.
      Fleet-average PM2.5 profiles are estimated for cold start and hot stabilized
      running emission processes. Fleet-average profiles are calculated to include
      emissions from deteriorated high-emitting vehicles that are expected to continue
      to contribute disproportionately to the fleet-wide PM2.5 emissions into the
      future. The profiles are calculated using a weighted average of the PM2.5
      composition according to the contribution of PM2.5 emissions from each class of
      vehicles in the on-road gasoline fleet in the Kansas City Metropolitan
      Statistical Area. The paper introduces methods to exclude insignificant
      measurements, correct for organic carbon positive artifact, and control for
      contamination from the testing infrastructure in developing speciation profiles.
      The uncertainty of the PM2.5 species fraction in each profile is quantified using
      sampling survey analysis methods. The primary use of the profiles is to develop
      PM2.5 emissions inventories for the United States, but the profiles may also be
      used in source apportionment, atmospheric modeling, and exposure assessment, and
      as a basis for light-duty gasoline emission profiles for countries with limited
      data. IMPLICATIONS: PM2.5 speciation profiles were developed from a large sample
      of light-duty gasoline vehicles tested in the Kansas City area. Separate PM2.5
      profiles represent cold start and hot stabilized running emission processes to
      distinguish important differences in chemical composition. Statistical analysis
      was used to construct profiles that represent PM2.5 emissions from the U.S.
      vehicle fleet based on vehicles tested from the 2005 calendar year Kansas City
      metropolitan area. The profiles have been incorporated into the EPA MOVES
      emissions model, as well as the EPA SPECIATE database, to improve emission
      inventories and provide the PM2.5 chemical characterization needed by CMAQv5.0
      for atmospheric chemistry modeling.

PMID- 24941702
TI  - Improvement of salinity in sewage sludge compost prior to its utilization as
      nursery substrate.
AB  - Soluble salts are enriched in sewage sludge compost because of their inherent
      derivation. Accordingly, the content of soluble salt in sludge compost is usually
      much higher than most seedlings can tolerate. To determine whether sludge compost
      is suitable for use as a nursery substrate, some experiments were conducted.
      Reduction of the electrical conductivity (EC) value could improve seed
      germination in saturated extract from sludge compost. In addition, water elution
      and mixing dilution with raw soil were all shown to be able to alleviate saline
      inhibition on seed germination and seedling growth, including stem diameter,
      seedling height, and above-ground weight. Overall, salinity is a crucial problem
      when sewage sludge compost is reused as a nursery substrate, and some effective
      and convenient approaches to reduce salt should be served prior to its reuse.
      IMPLICATIONS: Sewage sludge after being composted is usually reused as organic
      fertilizer or plant substrate. However, salt is the main problem during its
      reclamation. What is the highest salt level the seedling can tolerate? Which
      types of salts are effective in salinity of sludge-amended substrate? Meanwhile,
      can the salinity be reduced through water elution or soil mixing dilution? This
      paper is the first to investigate the salinity and its reduction of sewage sludge
      compost prior to its use in the development of nursery substrate.

PMID- 24941703
TI  - A model for interprovincial air pollution control based on futures prices.
AB  - Based on the current status of research on tradable emission rights futures, this
      paper introduces basic market-related assumptions for China's interprovincial air
      pollution control problem. The authors construct an interprovincial air pollution
      control model based on futures prices: the model calculated the spot price of
      emission rights using a classic futures pricing formula, and determined the
      identities of buyers and sellers for various provinces according to a
      partitioning criterion, thereby revealing five trading markets. To ensure
      interprovincial cooperation, a rational allocation result for the benefits from
      this model was achieved using the Shapley value method to construct an optimal
      reduction program and to determine the optimal annual decisions for each
      province. Finally, the Beijing-Tianjin-Hebei region was used as a case study, as
      this region has recently experienced serious pollution. It was found that the
      model reduced the overall cost of reducing SO2 pollution. Moreover, each province
      can lower its cost for air pollution reduction, resulting in a win-win solution.
      Adopting the model would therefore enhance regional cooperation and promote the
      control of China's air pollution. IMPLICATIONS: The authors construct an
      interprovincial air pollution control model based on futures prices. The Shapley
      value method is used to rationally allocate the cooperation benefit.
      Interprovincial pollution control reduces the overall reduction cost of SO2. Each
      province can lower its cost for air pollution reduction by cooperation.

PMID- 24941704
TI  - Childhood asthma acute primary care visits, traffic, and traffic-related
      pollutants.
AB  - Previous studies have found associations between traffic-related air pollution
      and asthma exacerbation in children, where exacerbations were measured according
      to emergency department visits and hospital admissions. Fewer studies have been
      undertaken that look at asthma exacerbations in a less severe primary care
      setting. Therefore, the authors sought to examine the associations between
      childhood asthma exacerbations, measured as acute visits to a primary care
      setting, and vehicular-traffic measures in a population of children aged 18 and
      under in the metropolitan Atlanta area. Statistical tests for differences of mean
      monthly visits for members with traffic measures above the median compared with
      below the median and for the upper quartile compared with the lower quartile were
      conducted. We also compared the odds of having one or more visits in a month for
      those who lived closer to a major roadway were compared with those who lived
      farther (greater than 300 m) from a major roadway. Poisson general linear
      modeling was used to determine associations between daily levels of acute visits
      for childhood asthma and traffic-related pollutants (zinc, EC [elemental carbon],
      and PM10 and PM2.5 [particulate matter with an aerodynamic diameter of < or = 10
      and < or = 2.5 microm, respectively]) for different levels of traffic and
      distance measures. This analysis found that both larger traffic volumes and
      smaller distances to the nearest major roadway were positively and significantly
      associated with larger numbers of childhood asthma visits, when compared with
      less traffic and larger distances. Our findings point to motor vehicle traffic as
      an important contributor to childhood asthma exacerbations. IMPLICATIONS:
      Previous studies have found associations between traffic-related air pollution
      and asthma exacerbation in children. However, these studies were mainly conducted
      in emergency department or hospital admission settings; little is known regarding
      less acute health effects. This analysis of the association between vehicular
      traffic measures and childhood asthma in a primary care setting suggests that
      motor vehicle traffic is a contributor to less acute asthma episodes in children.
      The present analysis of traffic-related air pollutants and childhood asthma were
      less conclusive, likely due to methods limitations outlined in the paper. The
      implication is that further evidence of adverse respiratory health effects in
      children due to motor vehicle traffic can be found in a primary care setting and
      similar studies should be considered.

PMID- 24941705
TI  - Migration of polycyclic aromatic hydrocarbons (PAHs) in urban treatment sludge to
      the air during PAH removal applications.
AB  - In the present study, the amounts of polycylic aromatic hydrocarbons (PAHs)
      penetrating into air during PAH removal applications from the urban treatment
      sludge were investigated. The effects of the temperature, photocatalyst type, and
      dose on the PAH removal efficiencies and PAH evaporation were explained. The
      sludge samples were taken from an urban wastewater treatment plant located in the
      city of Bursa, with 585,000 equivalent population. The ultraviolet C (UV-C) light
      of 254 nm wavelength was used within the UV applications performed on a specially
      designed setup. Internal air of the setup was vacuumed through polyurethane foam
      (PUF) columns in order to collect the evaporated PAHs from the sludge during the
      PAH removal applications. All experiments were performed with three repetitions.
      The PAH concentrations were measured by gas chromatography-mass spectrometry (GC
      MS). It was observed that the amounts of PAHs penetrating into the air were
      increased with increase of temperature, and more than 80% of PAHs migrated to the
      air consisted of 3-ring compounds during the UV and UV-diethylamine (DEA)
      experiments at 38 and 53 degrees C. It was determined that 40% decrease was
      ensured in sigma12 (total of 12) PAH amounts with UV application and 13% of PAHs
      in sludge penetrated into the air. In the UV-TiO2 applications, a maximum 80% of
      sigma12 PAH removal was obtained by adding 0.5% TiO2 of dry weight of sludge. The
      quantity of PAH penetrating into air did not exceed 15%. UV-TiO2 applications
      ensured high levels of PAH removal in the sludge and also reduced the quantity of
      PAH penetrating into the air. Within the scope of the samples added with DEA,
      there was no increase in PAH removal efficiencies and the penetration of PAHs
      into air was not decreased. In light of these data, it was concluded that UV-TiO2
      application is the most suitable PAH removal alternative that restricts the
      convection of PAH pollution.

PMID- 24941706
TI  - Photocatalytic reduction of carbon dioxide to methanol and formic acid by
      graphene-TiO2.
AB  - Graphene-TiO2 was obtained by reduction of graphite oxide by the hydrothermal
      method. Using photocatalytic activity to reduce carbon dioxide to methanol and
      formic acid was investigated in this study. The results show that the graphene
      loading affects the absorption of light in the visible light region. A larger
      surface area can also improve the catalytic activity. The largest yield of
      methanol and formic acid, under light of 365 nm, can reach 160 and 150 micromol
      g(-1), respectively with 8.5% graphene loading. An increase in graphene loading
      can enhance photocatalytic performance, but too much will also decrease the
      reduction efficiency by shielding the light from reaching the catalytic surface.
      The effect of pH was also investigated. The mechanism of the reaction was also
      discussed in this study. IMPLICATIONS: Graphene-TiO2 hybrids were prepared by the
      hydrothermal method. Surface area and visible light adsorption increased with the
      graphene loading. Increased graphene loading improved the methanol and formic
      acid production. Too much graphene loading will decrease the reduction
      efficiency. The effect of pH shows that the HCO3- species prefers the formation
      of formic acid. The mechanism of the reaction was also discussed in this study.

PMID- 24941708
TI  - Classification and comparison of municipal solid waste based on thermochemical
      characteristics.
AB  - Municipal solid waste (MSW) has been normally sorted into six categories, namely,
      food residue, wood waste, paper textiles, plastics, and rubber In each category,
      materials could be classified further into subgroups. Based on proximate and
      ultimate analysis and heating value, statistical methods such as analysis of
      variance (ANOVA) and cluster analysis were applied to analyze the characteristics
      of MSW in every subgroup and to try to distinguish their relative properties. The
      chemical characteristics analysis of MSW showed that polyethylene (PE),
      polypropylene (PP), and polystyrene (PS) had the highest volatile matter content,
      with almost no ash and fixed carbon, while polyethylene terephthalate (PET) had
      high carbon content but low hydrogen content. Bones and vegetables had the
      highest ash content, while nutshells and rubber had the highest fixed carbon
      content. Paper and starch food had the highest oxygen content, and wool and bones
      had the highest nitrogen and sulfur content. Polyvinyl chloride (PVC) had the
      highest chlorine content at about 55%. PE, PP and PS had the highest heating
      value, followed by chemical products such as rubber and chemical fiber.
      Conversely, paper, vegetables and bones had the lowest heating value. The results
      of cluster analysis of MSW components showed that fruit peel, weeds, wood,
      bamboo, leaves and nutshells could be classified as the lignocellulose category;
      starch food, cotton, toilet paper, printing paper and cardboard could be
      classified as the glucose monomer category; wood and chemical fiber could be
      classified as the high nitrogen and sulfur category; and PE, PP, and PS could be
      cluster as the polyolefin category. IMPLICATIONS: The yield of municipal solid
      waste (MSW) is constantly increasing and waste to energy (WTE) has been used
      extensively all over the world. During the processes of incineration, pyrolysis,
      or gasification, the impact of physical and chemical properties of MSW is of
      great significance. However, the traditional classification of MSW is too general
      to provide more detailed information in many investigations. It is necessary to
      perform the investigation of characteristics of combustible MSW to distinguish
      different categories of MSW and find out their subclassification.

PMID- 24941707
TI  - Synthesis of high-purity Na-A and Na-X zeolite from coal fly ash.
AB  - Coal fly ash (CFA) was used as a raw material for the synthesis of zeolite
      molecular sieve. The synthesis began with the pretreatment of CFA to remove
      impurities (e.g., Fe2O3, CaO, etc.) under various acid types (HCl, H2SO4, and
      HNO3) and acid/CFA ratios (5-25 mL(acid)/g(CFA)). High product purity (up to 97%)
      was achieved with HCl (20%wt), and acid/CFA ratio of 20 mL(HCl)/g(CFA). The
      treated CFA was then converted to zeolite by the fusion reaction under various
      Si/Al molar ratios (0.54-1.84). Zeolite type A was synthesized when the Si/Al
      molar ratios were lower than 1, whereas sodium aluminum silicate hydrate was
      formed when the Si/Al molar ratio were higher than 1. The highest water
      adsorption performance of the zeolite product, i.e., the outlet ethanol
      concentration of 99.9%wt and the specific adsorption capacity of 2.31 x 10(-2)
      g(water)/g(zeolite), was observed with the Si/Al molar ratio of 0.82. The zeolite
      was tested for its water adsorption capacity repeatedly 10 times without
      deactivation. IMPLICATIONS: This work evaluated the technical feasibility in the
      conversion of CFA to zeolite, which would help reduce the quantity of waste
      needed to be landfilled. This adds value to the unwanted material by converting
      it into something that can be further used. The synthesized products were shown
      to be quite stable as water adsorbent for the dehydration of ethanol solution.

PMID- 24941709
TI  - Pathophysiology and management of post resection liver failure.
AB  - Post resection liver failure (PRLF) is defined by the occurrence of jaundice,
      coagulopathy and encephalopathy after liver resection. When PRLF is present, it
      has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%.
      For having a healthy regeneration of the liver remnant an adequate number of
      hepatocytes and nonparenchymal cells, a normal functional and regenerative
      capacity and also a good accommodation of haemodynamic changes without congestion
      are needed. To avoid the presence of PRLF ongoing parenchymal damage after the
      liver resection should be avoided. So, ischemia reperfusion injury should be
      minimalized, infection and sepsis should be treated immediately and small for
      size syndrome should be avoided.

PMID- 24941710
TI  - Focal nodular hyperplasia and hepatocellular adenoma: current views.
AB  - Focal Nodular Hyperplasia (FNH) is a rare benign hepatic lesion believed to
      generate upon a hyperplastic response of the hepatocyte. Hepatocellular Adenoma
      (HA) occurs predominantly in young women receiving oral contraceptive medication.
      These two lesions have drawn significant attention throughout the recent years
      due to their specific clinical and pathological features as well as their
      challenging management. Although Focal Nodular Hyperplasia is managed
      conservatively in the majority of cases, it can albeit pose a difficult
      diagnostic dilemma. On the other hand, Hepatocellular Adenoma can be complicated
      with catastrophic hemorrhage or malignant transformation and therefore mandates
      surgical excision in many cases. The aim of this work is to review the current
      literature pertaining to these two clinical entities regarding their
      pathogenesis, diagnostic approach and genetics, as well as to shed light on
      specific differential diagnostic issues arising in many cases these lesions are
      encountered.

PMID- 24941711
TI  - Abdominal injuries after high falls: high incidence and increased mortality.
AB  - BACKGROUND: Falls from height are a major cause of morbidity and mortality.
      Injuries to the extremities and head are common. However, little has been
      reported on abdominal injuries or their treatment. This study aims to assess the
      abdominal injuries, treatment, and mortality after falls from height. METHODS: We
      searched our hospital's Trauma registry from January 2004 through December 2007
      and identified all patients who fell from five meters or higher. Additional data
      was extracted from medical records, radiology reports, and operation reports.
      RESULTS: One hundred and thirty-nine patients (median age 31 years) were
      included. There were 106 men and 33 women. Forty-one patients had abdominal
      injuries. Thirteen patients had a retroperitoneal hematoma, eleven had a liver
      laceration, nine had a kidney laceration, and eight had a spleen laceration.
      Eleven patients required emergency laparotomy and/or endovascular stenting or
      coiling to stop the bleeding. Patients with abdominal injuries had a tenfold
      higher mortality than those without abdominal injuries (19.5% versus 2.0%).
      CONCLUSION: Abdominal injuries were common and associated with a tenfold increase
      in mortality.

PMID- 24941712
TI  - Beclin 1 is highly expressed in papillary thyroid carcinoma and correlates with
      lymph node metastasis.
AB  - BACKGROUND: Autophagy is believed to be important in tumorigenesis and tumor
      progression. The human beclin-1 gene, a key regulator of autophagy formation,
      located on chromosome 17q21, has been identified as the mammalian orthologue of
      Atg6 (autophagy-related gene) and may be a haploinsufficient tumor suppressor
      gene. Loss of expression or point mutation could serve as a mechanism of loss of
      beclin-1 tumor suppressor function in cancers. However, our recent study revealed
      that point mutation of the beclin-1 gene is a rare event in papillary thyroid
      carcinoma (PTC). METHODS: We investigated the expression of beclin-1 in human
      PTC. Tissue samples from 86 cases of papillary thyroid carcinoma were used for
      the present study. 57 cases of papillary thyroid carcinoma were with lymph node
      metastasis. The expression of beclin-1 in tumor, normal tissue adjacent to tumor,
      distant normal tissue, metastatic lymph node and normal lymph node was examined
      with immunohistochemistry. The beclin-1 expression between tumor and normal
      tissue, metastatic and normal lymph node was also analyzed. RESULTS: The
      expression of beclin-1 was detected in 88.4% (76/86) of the tumors and 98.2%
      (56/57) of metastatic lymph nodes. In contrast, normal tissues adjacent to tumor,
      distant normal tissues and normal lymph nodes showed no or very weak expression
      of beclin-1. Beclin-1 was significantly correlated with tumorigenesis and lymph
      node metastasis in human PTC. CONCLUSIONS: High expression of beclin-1 in PTC and
      metastatic lymph node suggest that neo-expression of beclin-1 may play a role in
      tumorigenesis and lymph node metastasis in human PTC.

PMID- 24941713
TI  - Aortobifemoral bypass via paramedian incision and retroperitoneal approach for
      aortoiliac occlusive disease.
AB  - INTRODUCTION: Aorto-bifemoral graft bypass operation is performed in the surgical
      treatment of aortoiliac occlusive occlusive disease. The conventional standard
      technique used is the median laparotomy and transperitoneal approach. In this
      study we evaluated the outcome of aortobifemoral bypass operation via paramedian
      and retroperitoneal approach. METHODS: 17 patients were operated upon for
      aortobiiliac occlusive disease from January 2008 through December 2011. Mean age
      of the patients was 61.8 +/- 8.9 (47-78 years). All patients except for one were
      operated via left paramedian vertical 8 to 10 cm incision approximately 6 cm to
      the left or right of midline, extending from a few centimeters above the
      umbilicus to just above the symphysis pubis. The aortas were reached
      retroperitoneally through this incision. RESULTS: There was one postoperative
      death secondary to pulmonary complications. No intraoperative or postoperative
      surgical complication had occured. All patients were discharged from the hospital
      on antiplatelet therapy. Graft patency was evaluated by means of physical
      examination on discharge. Upon the patients' hospital discharge, primary graft
      patency was 100%. The ankle-brachial indices measured from both the right and
      left sides were 0.51 +/- 0.10 preoperatively and 0.99 +/- 0.14 postoperatively (p
      <0.001). DISCUSSION: A lot of complications can be observed due to median
      laparotomy such as evisceration, incisional hernia, peritonitis, bride ileus. We
      believe that retroperitoneal approach for aorto-bifemoral graft bypass operation
      in the patients with bilateral iliac arterial occlusive disease is a well
      tolerated minimally invasive operation when compared to the conventional median
      laparotomy approach.

PMID- 24941714
TI  - Mitral regurgitation and coronary artery bypass surgery: comparison of mitral
      valve repair and replacement.
AB  - BACKGROUND: The aim of this retrospective study was to determine if there is a
      statistically significant difference (p < or = 0.05) between mitral valve repair
      (MVRp) with concomitant surgical revascularization of the myocardium (CABG) and
      mitral valve replacement (MVR) with concomitant CABG, considering the duration of
      surgery, early postoperative morbidity, in-hospital mortality, length of stay in
      the Intensive Care Unit (ICU) and overall in-hospital stay. METHODS: Between
      January 1st 2006 and December 31st 2008, 75 patients underwent surgery for mitral
      regurgitation and ischemic heart disease. Patients were divided in two groups
      determined by the procedure that was performed on the mitral valve (MVRp + CABG
      group had 34 patients, MVR + CABG group had 41 patients). All the patients were
      operated by the same surgical team and received the usual anaesthesia protocol.
      RESULTS: Patients in the MVR + CABG group had statistically significant higher
      EuroSCORE risk levels, higher NYHA status and higher incidence of postoperative
      low cardiac output syndrome (LCOS). Neurological complications showed
      statistically significant higher incidence in the MVRp + CABG group. There was no
      statistically significant difference in regard to in-hospital mortality between
      these two groups. Patients in the MVR + CABG group had statistically significant
      longer in-hospital stay. CONCLUSIONS: Mitral valve repair and mitral valve
      replacement are complementary methods considering early postoperative morbidity
      and mortality. Higher incidence of LCOS and in-hospital stay in the MVR + CABG
      group was to be expected on behalf of poorer preoperative status.

PMID- 24941715
TI  - The use of a self-gripping mesh in open inguinal hernia repair. A prospective
      observational single surgeon study.
AB  - BACKGROUND: The Lichtenstein repair is a well standardized surgical technique
      that can mostly be performed in day-clinic under loco-regional anesthesia. The
      major concern is the chronic pain reported after mesh suture fixation. We studied
      the practical and clinical aspects of a Lichtenstein repair using the semi
      resorbable self-fixating Parietex ProGrip mesh. METHODS: Consecutive patients
      with inguinal hernia were operated according to the Lichtenstein technique using
      Parietex ProGrip. Complications were assessed. Pain and discomfort were evaluated
      at discharge, and at 1 and 4 weeks and minimum 6 months after the intervention.
      RESULTS: 320 patients were included in the study. No intra-operative
      complications or difficulties occurred. Mean operating time was 36 minutes (range
      20-65 minutes). 87.5% of the patients (280) were discharged at day of operation,
      11.9% (38 patients) had an overnight stay and 0.6% (2 patients) stayed two
      nights. Mean number of days of analgesic use is 2.1. At the 1 week follow-up
      visit, minor pain or discomfort was reported by 45 patients (14%) and at 4 weeks
      11 patients (3.4%) still had minor discomfort. At 6 months 1 patient suffered
      from persisting local numbness. Two recurrences were noted, both were re
      operated. CONCLUSIONS: This observational study confirms earlier findings with
      this semi-resorbable self-gripping mesh regarding operation time, complications
      and recurrence. The open Lichtenstein hernia repair with the semi-resorbable self
      gripping Parietex Progrip mesh seems to offer a reliable alternative for the
      treatment of inguinal hernia with benefits on operating time as well as on
      postoperative pain.

PMID- 24941716
TI  - Effects of variable courses of inguinal nerves on pain in patients undergoing
      Lichtenstein repair for inguinal hernia: preliminary results.
AB  - BACKGROUND: Problems due to damage to ilioinguinal and iliohypogastric nerves
      which have many variations following surgery for inguinal hernia cause additional
      work leave and delay in return to daily life. We aimed to compare outcomes of
      nerve identification and preservation with a careful dissection during
      Lichtenstein repair of inguinal hernia between normal courses of inguinal based
      nerves and variable courses of inguinal based nerves. METHODS: This is a
      prospective study and 116 adult male patients with primary inguinal hernia were
      operated between December 2009 and June 2010. The patients with a normal nerve
      trace identified on exploration were assigned into Group Normal Course and those
      with variable nerve course were assigned into Group Variable Course. These two
      groups were compared in terms of demographic features, preoperative and
      postoperative variables, return to work and daily routines, duration of
      fulfilling personal needs, visual analogue scores before and one and six months
      after surgery, four-point verbal-rank scale scores, numbness and patient
      satisfaction. RESULTS: Out of 116 patients, 70 (60.3%) had variable courses of
      the nerves and were assigned into the Group Variable Course and 46 (39.7%) had
      normal courses of the nerves and were assigned into Group Normal Course. A single
      stem for both nerves over spermatic cord (21.6%) and acute infero-lateral
      angulation of the Ilioinguinal nerve in close contact with and parallel to the
      Superficial Inguinal Ring fibers at exit (15.5%) were the most observed
      variations. Duration of surgery was significantly longer in Group Variable Course
      (p <0.001). Numbness was also slightly higher in this group one month after
      surgery. This difference nearly disappeared six months after surgery. CONCLUSION:
      Although careful and gentle exploration increases the duration of surgery and
      early neuropraxia, identification and preservation of nerves during surgery for
      inguinal hernia help to achieve similar outcomes in both patients with a normal
      course of nerves and those with a variable course of nerves.

PMID- 24941718
TI  - The correlation between ultrasonography and histopathology in the management of
      gall bladder polyps.
AB  - INTRODUCTION: The diagnosis of gall bladder polyps has increased greatly due to
      widespread implementation of abdominal ultrasound. PATIENTS AND METHODS: Between
      February 2005 and February 2010 a total of 39 laparoscopic cholecystectomies were
      performed for suspected gall bladder polyps. We retrospectively analysed these
      patients pre-operative ultrasound and histopathology report. RESULTS: The study
      comprised 10 male and 29 female symptomatic patients with a mean age of 51.4
      years. Histopathology demonstrated seven true polyps and 23 pseudopolyps. There
      were no cases of malignant specimens and nine cases of chronic cholecystitis. The
      positive predictive value (PPV) of ultrasonography for gall bladder polyps was
      0.77 and the PPV for true polyps 0.18. CONCLUSION: PPV for the identification of
      true gallbladder polyps using ultrasound remains very low at 0.18. We suggest
      that more advanced imaging modalities are required to improve this figure and
      enhance patient management.

PMID- 24941717
TI  - Comparison of laparoscopic and open adrenalectomy.
AB  - Laparoscopic adrenalectomy is one of the most significant advances in the past 20
      years for treating adrenal disorders. Laparoscopic adrenalectomy has been the
      golden standard procedure for all adrenal pathologies since it was first defined
      in 1992. Laparoscopic adrenalectomy is preferred and has advantages such as less
      postoperative pain, earlier resumption of oral intake, shorter hospital stay,
      earlier return to normal life and better esthetical results. In our study we
      compared morbidity and mortality rates of laparoscopic and open adrenalectomy
      cases. MATERIAL AND METHODS: In Ankara University Faculty of Medicine General
      Surgery department 92 cases of adrenalectomy were performed between january 2000
      july 2006. The patients were evaluated for age, sex, duration of perioperative
      hospital stay, resumption of oral intake, duration of operation, surgical wound
      infection, conversion rate and complications. RESULTS: In patients who underwent
      laparoscopic surgery, rate of conversion to open surgery was 9.3% (4 patients).
      The mean operative duration in the laparoscopic adrenalectomy group was 150
      minutes and the mean operative duration in the open adrenalectomy group was 120
      minutes (p = 0.001). Surgical wound infection rate was 6% in the open
      adrenalectomy group and 2% in the laparoscopic adrenalectomy group. Mean
      perioperative hospital stay was 7.1 days in the open adrenalectomy group and 5.1
      days in the laparoscopic adrenalectomy group. Time to resumption of oral intake
      was 2.42 days in the open adrenalectomy group and 1.05 days in the laparoscopic
      adrenalectomy group (p = 0.001). There was no perioperative mortality in none of
      the groups. CONCLUSION: Laparoscopic adrenalectomy is the golden standard
      surgical treatment for benign and selected malignant adrenal diseases.
      Laparoscopic adrenalectomy is a safe and effective technique and has advantages
      such as less postoperative pain, earlier resumption to oral intake, shorter
      hospital stay, earlier return to normal life and better esthetical results
      compared to open adrenalectomy.

PMID- 24941719
TI  - Transanal resection: a novel approach.
AB  - Due to the increase in screening programs, more rectal polyps and early rectal
      cancers are detected. Transanal resection of these lesions is less invasive than
      a transabdominal approach. Transanal endoscopic microsurgery (TEM) has gained a
      lot of interest, but the technique has several drawbacks such as the expensive
      instrumentation and considerable learning curve. With the evolution of single
      incision laparoscopic surgery (SILS), laparo-endoscopic single-site surgery
      (LESS) and natural orifice transluminal endoscopic surgery (NOTES), new devices
      have become available. This led to the development of a hybrid technique of
      transanal surgery. The technique combines a transanal approach, a SILS port and
      standard laparoscopic instruments. We used this technique in 2 cases.

PMID- 24941720
TI  - Multiple abdominal cysts in a patient with Gorlin-Goltz syndrome: a case report.
AB  - A rare case of symptomatic mesenteric cysts in a patient with Gorlin-Goltz
      syndrome, associated with various neoplasms, is presented. The patient, known
      with Gorlin-Goltz syndrome, consulted with increasingly severe abdominal pain and
      large abdominal cysts. At surgery, the cysts were excised and the postoperative
      course was uneventful. In conclusion, this case reminds clinicians to always
      maintain a wide differential diagnosis when dealing with patients known with
      Gorlin-Goltz syndrome.

PMID- 24941721
TI  - Blunt injury to the ileum following a bull attack: case report.
AB  - Detection of small bowel injury after blunt abdominal trauma can be challenging.
      Occurrence is rare, but delay in the diagnosis and surgical repair increases
      patient morbidity and mortality. We present a case of crushing-type injury of the
      distal ileum in a farmer who has been attacked by a Highland bull. On arrival at
      the emergency department, physical examination and imaging modalities were
      reassuring. The maintenance of high clinical suspicion led us to perform an
      exploratory laparotomy that brought the ileal perforation to light.

PMID- 24941722
TI  - Angiosarcoma of the breast: case report and review of the literature.
AB  - Skin lesions in a post-radiated breast should always be considered as possible
      angiosarcoma even if they mimic a traumatic lesion. Early detection by excisional
      biopsy followed by a mastectomy is necessary because of the high numbers of
      relapse if locally treated and possible deadly metastasis. We present a case of a
      cutaneous angiosarcoma occurred at lumpectomy site in a patient with a history of
      breast cancer and radiation of the breast and provide a review of the literature.

PMID- 24941723
TI  - Recurrent hyperparathyroidism caused by benign neoplastic seeding: two cases of
      parathyromatosis and a review of the literature.
AB  - BACKGROUND: Parathyromatosis is defined as small nodules of hyperfunctioning
      parathyroid tissue scattered in the soft tissues of the neck and/or mediastinum.
      Parathyromatosis may be primary, it may be aimed for when autotransplanting
      parathyroid tissue in secondary hyperparathyroidism, and it may occur after
      surgery for primary hyperparathyroidism (pHPT). In the latter cases
      parathyromatosis poses a diagnostic and therapeutic challenge. METHODS: To
      illustrate the clinical problem of parathyromatosis as a rare cause of recurrent
      disease after an operation for pHPT we describe two patients and performed a
      review of the literature for contributing factors. RESULTS: Two patients,
      previously treated for pHPT and having undergone multiple neck explorations had
      at their final operation numerous small nests of benign parathyroid tissue
      scattered throughout connective tissue of the neck. These findings concur with
      various previous cases reported in the reviewed literature. CONCLUSIONS: These
      cases illustrate that meticulous handling of parathyroid adenomas during surgical
      excision is of the utmost importance. Regardless of which operating technique is
      utilised, great emphasis must be placed on precautions towards ensuring the
      complete and above all the intact removal of the affected gland without capsular
      rupture. As parathymatosis is caused by seeding, which although extremely rare,
      it might very well result in the need for extensive reexploration.

PMID- 24941724
TI  - Internal hernia as a complication of congenital falciform ligament window.
AB  - Commonly, small bowel obstruction (SBO) is caused by either postoperative
      adhesions or external hernias. Internal hernias are rare, accounting for less
      than 2% of all cases of intestinal obstruction. An internal hernia through the
      falciform ligament is extremely uncommon and is usually secondary to a congenital
      or iatrogenic defect caused by trocars insertion. In this article, we report a
      case of SBO in a virgin abdomen that appeared to be caused by a congenital defect
      in the falciform ligament. A search of the literature was done identifying all
      reported cases of internal hernias caused by falciform ligament defect in order
      to guide diagnosis and management as well as avoidance of hernias caused by
      iatrogenic defects.

PMID- 24941725
TI  - Reality bites.

PMID- 24941726
TI  - Effective help for children exposed to domestic abuse.

PMID- 24941727
TI  - Living with eczema: Abigail's story.

PMID- 24941728
TI  - Red flag causes of vomiting in infants.
AB  - Vomiting is a common presentation in infants and is mostly due to a benign cause.
      Although vomiting is usually considered to be gastrointestinal in origin, it can
      be due to dysfunction of other organ systems, some of which may be life
      threatening. Community practitioners are often the first health professionals to
      come across these infants. They should assess these infants keeping in mind the
      'red flags'. Suspicion of a serious disorder should be followed by prompt
      referral to a medical professional. This article aims to highlight the commonly
      encountered causes of vomiting in infants and provides some suggestions to be
      followed by community practitioners while dealing with an infant presenting with
      vomiting.

PMID- 24941729
TI  - At a glance: scarlet fever in children.

PMID- 24941730
TI  - Gaining a fresh perspective.

PMID- 24941732
TI  - Onwards facing backwards: the rhetoric of science in nineteenth-century Greece.
AB  - The aim of this paper is to show how the Greek men of science negotiated a role
      for their enterprise within the Greek public sphere, from the institution of the
      modern Greek state in the early 1830s to the first decades of the twentieth
      century. By focusing on instances where they appeared in public in their official
      capacity as scientific experts, I describe the rhetorical schemata and the
      narrative strategies with which Greek science experts engaged the discourses
      prevalent in nineteenth- and early twentieth-century Greece. In the end, my goal
      is to show how they were neither zealots of modernization nor neutral actors
      struggling in isolated wastelands. Rather, they appear as energetic agents who
      used scientific expertise, national ideals and their privileged cultural
      positions to construct a rhetoric that would further all three. They engaged
      eagerly and consistently with emerging political views, scientific subjects and
      cultural and political events, without presenting themselves, or being seen, as
      doing anything qualitatively different from their peers abroad. Greek scientists
      cross-contextualized the scientific enterprise, situating it in the space in
      which they were active.

PMID- 24941731
TI  - William Harvey, Aristotle and astrology.
AB  - In this paper I argue that William Harvey believed in a form of astrology. It has
      long been known that Harvey employed a macrocosm-microcosm analogy and used
      alchemical terminology in describing how the two types of blood change into one
      another. This paper then seeks to examine a further aspect of Harvey in relation
      to the magical tradition. There is an important corollary to this line of
      thought, however. This is that while Harvey does have a belief in astrology, it
      is strongly related to Aristotle's views in this area and is quite restricted and
      attenuated relative to some contemporary beliefs in astrology. This suggests a
      more general thesis. While Harvey was amenable to ideas which we associate with
      the natural magic tradition, those ideas had a very broad range of formulation
      and there was a limit to how far he would accept them. This limit was largely
      determined by Harvey's adherence to Aristotle's natural philosophy and his
      Christian beliefs. I argue that this is also the case in relation to Harvey's use
      of the macrocosm-microcosm analogy and of alchemical terminology, and, as far as
      we can rely on the evidence, this informs his attitudes towards witches as well.
      Understanding Harvey's influences and motives here is important in placing him
      properly in the context of early seventeenth-century thought.

PMID- 24941733
TI  - Savage numbers and the evolution of civilization in Victorian prehistory.
AB  - This paper identifies 'savage numbers'--number-like or number-replacing concepts
      and practices attributed to peoples viewed as civilizationally inferior--as a
      crucial and hitherto unrecognized body of evidence in the first two decades of
      the Victorian science of prehistory. It traces the changing and often ambivalent
      status of savage numbers in the period after the 1858-1859 'time revolution' in
      the human sciences by following successive reappropriations of an iconic 1853
      story from Francis Galton's African travels. In response to a fundamental lack of
      physical evidence concerning prehistoric men, savage numbers offered a readily
      available body of data that helped scholars envisage great extremes of
      civilizational lowliness in a way that was at once analysable and comparable, and
      anecdotes like Galton's made those data vivid and compelling. Moreover, they
      provided a simple and direct means of conceiving of the progressive scale of
      civilizational development, uniting societies and races past and present, at the
      heart of Victorian scientific racism.

PMID- 24941734
TI  - 'Keeping in the race': physics, publication speed and national publishing
      strategies in Nature, 1895-1939.
AB  - By the onset of the Second World War, the British scientific periodical Nature-
      specifically, Nature's 'Letters to the editor' column--had become a major
      publication venue for scientists who wished to publish short communications about
      their latest experimental findings. This paper argues that the Nobel Prize
      winning physicist Ernest Rutherford was instrumental in establishing this use of
      the 'Letters to the editor' column in the early twentieth century. Rutherford's
      contributions set Nature apart from its fellow scientific weeklies in Britain and
      helped construct a defining feature of Nature's influence in the twentieth
      century. Rutherford's participation in the journal influenced his students and
      colleagues in the field of radioactivity physics and drew physicists like the
      German Otto Hahn and the American Bertram Borden Boltwood to submit their work to
      Nature as well, and Nature came to play a major role in spreading news of the
      latest research in the science of radioactivity. Rutherford and his colleagues
      established a pattern of submissions to the 'Letters to the editor' that would
      eventually be adopted by scientists from diverse fields and from laboratories
      around the world.

PMID- 24941735
TI  - The conquest of vitalism or the eclipse of organicism? The 1930s Cambridge
      organizer project and the social network of mid-twentieth-century biology.
AB  - In the 1930s, two concepts excited the European biological community: the
      organizer phenomenon and organicism. This essay examines the history of and
      connection between these two phenomena in order to address the conventional 'rise
      and-fall' narrative that historians have assigned to each. Scholars promoted the
      'rise-and-fall' narrative in connection with a broader account of the
      devitalizing of biology through the twentieth century. I argue that while limited
      evidence exists for the 'fall of the organizer concept' by the 1950s, the
      organicism that often motivated the organizer work had no concomitant fall--even
      during the mid-century heyday of molecular biology. My argument is based on an
      examination of shifting social networks of life scientists from the 1920s to the
      1970s, many of whom attended or corresponded with members of the Cambridge
      Theoretical Biology Club (1932-1938). I conclude that the status and cohesion of
      these social networks at the micro scale was at least as important as macro-scale
      conceptual factors in determining the relative persuasiveness of organicist
      philosophy.

PMID- 24941737
TI  - Writing, printing, speaking: Rhesus blood-group genetics and nomenclatures in the
      mid-twentieth century.
AB  - In the 1940s and 1950s, British and American journals published a flood of papers
      by doctors, pathologists, geneticists and anthropologists debating the virtues of
      two competing nomenclatures used to denote the Rhesus blood groups. Accounts of
      this prolonged and often bitter episode have tended to focus on the main
      protagonists' personalities and theoretical commitments. Here I take a different
      approach and use the literature generated by the dispute to recover the practical
      and epistemic functions of nomenclatures in genetics. Drawing on recent work that
      views inscriptions as part of the material culture of science, I use the Rhesus
      controversy to think about the ways in which geneticists visualized and
      negotiated their objects of research, and how they communicated and collaborated
      with workers in other settings. Extending recent studies of relations between
      different media, I consider the material forms of nomenclatures, as they were
      jotted in notebooks, printed in journals, scribbled on blackboards and spoken out
      loud. The competing Rhesus nomenclatures had different virtues as they were
      expressed in different media and made to embody commitments to laboratory
      practices. In exploring the varied practical and epistemic qualities of
      nomenclatures I also suggest a new understanding of the Rhesus controversy
      itself.

PMID- 24941736
TI  - 'Saving the lives of our dogs': the development of canine distemper vaccine in
      interwar Britain.
AB  - This paper examines the successful campaign in Britain to develop canine
      distemper vaccine between 1922 and 1933. The campaign mobilized disparate groups
      around the common cause of using modern science to save the nation's dogs from a
      deadly disease. Spearheaded by landed patricians associated with the country
      journal The Field, and funded by dog owners and associations, it relied on
      collaborations with veterinary professionals, government scientists, the Medical
      Research Council (MRC) and the commercial pharmaceutical house the Burroughs
      Wellcome Company (BWC). The social organization of the campaign reveals a number
      of important, yet previously unexplored, features of interwar science and
      medicine in Britain. It depended on a patronage system that drew upon a large
      base of influential benefactors and public subscriptions. Coordinated by the
      Field Distemper Fund, this system was characterized by close relationships
      between landed elites and their social networks with senior science
      administrators and researchers. Relations between experts and non-experts were
      crucial, with high levels of public engagement in all aspects of research and
      vaccine development. At the same time, experimental and commercial research
      supported under the campaign saw dynamic interactions between animal and human
      medicine, which shaped the organization of the MRC's research programme and
      demonstrated the value of close collaboration between veterinary and medical
      science, with the dog as a shared object and resource. Finally, the campaign made
      possible the translation of 'laboratory' findings into field conditions and
      commercial products. Rather than a unidirectional process, translation involved
      negotiations over the very boundaries of the 'laboratory' and the 'field', and
      what constituted a viable vaccine. This paper suggests that historians reconsider
      standard historical accounts of the nature of patronage, the role of animals, and
      the interests of landed elites in interwar British science and medicine.

PMID- 24941738
TI  - Unsuitable for ladies?

PMID- 24941739
TI  - [Progress in biosythesis of diaminopentane].
AB  - Air pollution and global warming are increasingly deteriorating. Large amounts of
      polyamides derived from fossil fuel sources are consumed around the world.
      Cadaverine is an important building monomer block of bio-based polyamides, thus
      biotechnological processes for these polymers possess enormous ecological and
      economical potential. Currently, the engineered strains for biological production
      of cadaverine are Corynebacterium glutamicum and Escherichia coli. We review here
      the latest research progress of biosynthesis of cadaverine including metabolism
      of cadaverine in microorganisms, key enzymes and transport proteins in cadaverine
      synthesis pathway, optimum pathways and cadaverine yields.

PMID- 24941740
TI  - [Effect of over-expressed miR-155 on inhibiting C2C12 myogenic differentiation].
AB  - To clarify the function and molecular mechanism of miR-155 in myogenic
      differentiation of C2C12, we constructed adenovirus over-expression vector of miR
      155, then C2C12 cells were infected by adenovirus and induced myogenic
      differentiation. First, we observed the morphology of C2C12 after
      differentiation. Then the mRNA and protein expressions of myogenic markers (MyoD,
      MyoG and MyHC) were detected by qPCR and western blotting. Subsequently, the dual
      luciferase reporter gene assay was carried out to validate putative target gene
      (TCF4) of miR-155. Meanwhile, mRNA level of TCF4 was analyzed after over
      expressing miR-155. The results show that over-expressed miR-155 reduced myotubes
      formation. Moreover, the mRNA and protein expression of MyoG and MyHC decreased
      significantly (P < 0.01). Further research demonstrated miR-155 bound the one
      (4532-4538) of three putative sites (1487-1493,1516-1522, 4532-4583) of TCF4 by
      luciferase reporter gene assay and the mRNA level of TCF4 decreased notably (P <
      0.05). The data suggest that miR-155 inhibited myogenic differentiation of C2C12
      through targeted TCF4.

PMID- 24941741
TI  - [Method for Japanese encephalitis virus NS3 protease activity analysis and high
      throughput screening assay for inhibitors].
AB  - Japanese encephalitis virus (JEV) is a single-stranded and positive-sense RNA,
      which has a single ORF (open reading frame), encoding a polyprotein precursor.
      Non-structural protein 3 (NS3) plays an important role in processing the
      polyprotein precursor and has become an important drug target of flavivirus. In
      this study, NS2BH-NS3 gene was amplified by PCR and subcloned to the prokaryotic
      expression plasmid, resulting pET30a-NS2BH-NS3. The fusion protein was expressed
      in Escherichia coli BL21 (DE3) in soluble form after induction by Isopropyl beta
      D-1-Thiogalactopyranoside (IPTG). The recombinant protein was purified by Ni-NTA
      affinity column. Then a fluorescence resonance energy transfer (FRET) method was
      used to determine enzymatic activity and the assay conditions were optimized.
      After screening 113 compounds, we found two compounds inhibiting the activity of
      NS2BH-NS3. This study provides a convenient and cost-effective method for
      screening of JEV NS3 protease inhibitor.

PMID- 24941743
TI  - [Cloning and analysis of promoter of pig copper zinc superoxide dismutase gene
      (CuZnSOD)].
AB  - Pig copper zinc superoxide dismutase (CuZnSOD) is an important antioxidant
      enzyme. Some studies focused on the function of CuZnSOD gene, but the
      transcriptional regulation of the CuZnSOD gene is not yet fully elucidated.
      Therefore, the aims of the study were to determine the core promoter region and
      to explore its mechanism of transcriptional regulation. The 853 bp DNA sequence
      of 5'-flanking promoter was amplified by performing PCR. A series of CuZnSOD
      promoter fragments with gradually truncated 5'-end were produced by nested PCR
      and inserted into pGL3-Basic vector. The activities of the promoters were
      measured by the dual-luciferase assay system after transient transfection into
      the NIH/3T3 cells. The results demonstrated that there were 2 potential
      transcription start sites in the regions from initiation codon to -87 bp and -266
      bp, respectively. The region from -383 bp to +67 bp in CuZnSOD gene promoter
      showed higher activity than other regions, and further deletion analysis
      demonstrated that the region from -75 bp to -32 bp contained an essential
      promoter sequence for pig CuZnSOD gene transcription. In addition, several
      potential transcription factor binding sites were predicted with bioinformatics
      method. These results suggest that these transcription factor binding sites may
      be involved in the transcriptional regulation of CuZnSOD gene.

PMID- 24941742
TI  - [Construction and specificity of porcine bmp15 gene reporter vector].
AB  - The aim of this study is to identify the express specificity of bone
      morphogenetic protein 15 (Bmp15) in porcine. The pBMP15-EGFP reporter vector was
      constructed from the 2.2 kb fragment of porcine bmp15 promoter to trace the
      differentiation process of stem cells into oocyte-like cells. We used porcine
      ovary and Chinese Hamster Ovary cell line (CHO), mouse myoblast cell line (C2C12)
      and porcine amniotic fluid stem cell (pAFSC) to investigate the expression and
      regulation of this gene via RT-PCR, immunofluorescence, cell transfection, and
      microinjection methods. We also used single layer cell differentiation to detect
      the application potential of bmp15. The results show that bmp15 gene was
      specifically expressed in the porcine ovary and CHO rather than in C2C12 and
      pAFSC. In addition, the characteristic of tissue-specific of Bmp15 was detected
      on CHO instead of other cell lines by transient transfection. We also detected
      the expression of Bmp15 in oocyte at different development stages by
      immunofluorescence of fixed paraffin-embedded ovary sections. Furthermore,
      microinjection results show that bmp15 expressed in oocytes at 18 h of maturation
      in vitro, and continued up to 4-cell stage embryos. Most importantly, we found
      that the expression of Bmp15 started at day 12 after inducing pAFSC into oocyte
      like cells by transfection; green fluorescent was visible in round cell masses.
      It indicated that bmp15 has the expression specificity and the pBMP15-EGFP
      reporter vector can be used to trace Bmp15 action in the differentiation of stem
      cells into germ cells.

PMID- 24941744
TI  - [Metabolomics analysis of taxadiene producing yeasts].
AB  - In order to study the inherent difference among terpenes producing yeasts from
      the point of metabolomics, we selected taxadiene producing yeasts as the model
      system. The changes of cellular metabolites during fermentation log phase of
      artificial functional yeasts were determined using metabolomics methods. The
      results represented that compared to W303-1A as a blank control, the metabolites
      in glycolysis, tricarboxylic acid cycle (TCA) cycle and several amino acids were
      influenced. And due to the changes of metabolites, the growth of cells was
      inhibited to a certain extent. Among the metabolites identified, citric acid
      content in taxadiene producing yeasts changed the most, the decreasing amplitude
      reached 90% or more. Therefore, citric acid can be a marker metabolite for the
      future study of artificial functional yeasts. The metabolomics analysis of
      taxadiene producing yeasts can provide more information in further studies on
      optimization of terpenes production in heterologous chassis.

PMID- 24941746
TI  - [Immunological characteristics of Mycobacterium tuberculosis antigen Rv2628].
AB  - Antigen Rv2628 of Mycobacterium tuberculosis is associated with latent
      tuberculosis infection. In this study, Rv2628 was prokaryotic expressed and
      purified, its immunological characteristics was evaluated with macrophage cell
      line RAW264.7 and BALB/c mice. The results show that Rv2628 was mainly expressed
      in form of inclusion body confirmed by SDS-PAGE, and could react with rabbit anti
      H37Rv polyclonal antibody detected by Western blotting assay, indicating that the
      protein had an effective immunoreactivity. The interactions between Rv2628 and
      macrophage cell line RAW264.7 confirmed that it could effectively induce cells to
      produce pro-inflammatory cytokines, the relative expression level of IL-6 mRNA
      was higher than the control group in 1-12 h. BALB/c mice were subcutaneously
      immunized with Rv2628 protein, the production of IFN-gamma and IL-4 in the spleen
      cells was determined by Sandwich ELISA, in the Rv2628 immunized group, the level
      of IFN-gamma was significantly higher than that of IL-4 (P < 0.000 1). It
      indicated the protein induced Th1-tendency immune responses. At the same time,
      Rv2628(11-30) peptide used as coating antigen, the murine serum antibody titer
      detected by indirect-ELISA was 1:1 600, which demonstrated that Rv2628 could also
      induce humoral immune responses. In summary, Rv2628 could induce specific pro
      inflammatory cytokines, affectively induce strongly Th1-tendency immune response
      and humoral response, it could be a potential target for developing subunit
      vaccine against TB. In addition, it laid foundation for probing the cross-talk
      between M. tb and host.

PMID- 24941745
TI  - Characterization and subcellular localization of two 14-3-3 genes and their
      response to abiotic stress in wheat.
AB  - In order to investigate biological functions of the 14-3-3 genes and their
      response to abiotic stress, two cDNAs (designated as Ta14R1 and Ta14R2) encoding
      putative 14-3-3 proteins were isolated from wheat by PCR and rapid amplification
      of cDNA end (RACE) technique. The cDNA of Ta14R1 is 999bp and encodes a protein
      of 262 amino acids, while the cDNA of Ta14R2 is 897bp in length and encodes a
      protein of 261 amino acids. Transient expression assays using Ta14R1/Ta14R2-GFP
      fusion constructs indicated that Ta14R1 and Ta14R2 were located in cytoplasm and
      cell membrane but not in chloroplasts. Real-time quantitative (RT-PCR) analysis
      revealed that Ta14R1 and Ta14R2 were differentially expressed in wheat tissues
      and significantly up-regulated in roots and shoots 1d after germination,
      indicating they may play a role in process of seed germination. The expression of
      the two genes in roots and leaves were significantly induced by plant hormone
      ABA, as well as heat, cold and drought treatments, suggesting that the two 14-3-3
      genes in wheat may be involved in ABA dependent stress-responding pathway and
      response to heat, cold and drought stress.

PMID- 24941747
TI  - [Construction and expression of a eukaryotic vector co-expressing immunodominant
      antigens of CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis].
AB  - CFP10, ESAT6, Antigen 85A (Ag85A) and antigen 85B (Ag85B) are the key
      immunodominant antigens of Mycobacterium tuberculosis. In order to construct a
      eukaryotic vector able to co-express the four genes in one vector, we amplified
      the target gene fragments encoding the CFP10, ESAT6, Ag85A and Ag85B antigens and
      inserted them into the multicloning site of the shuttle plasmid vector pcDNA3.1
      (+), of which the CFP10 and ESAT6 encoding genes were in frame fused with a
      linker encoding (Gly4Ser)3 residue, before the fused gene was inserted downstream
      of CMV promoter with a bovine growth hormone poly A(BGH pA) sequence at the 3'
      end; Ag85A and Ag85B encoding genes were fused with a separation of internal
      ribosome entry site (IRES) sequence before the fused gene cassette was inserted
      downstream of RSV promoter with a BGH pA sequence at the 3'-end. The final
      plasmid containing all four genes was confirmed by sequence analysis and
      designated as pcDNA-CFP10-ESAT6-Ag85A-Ag85B (pcDNA-CEAB). In order to verify the
      ability of this construct to express target proteins, we then transfected the
      recombinant plasmid into Human embryonic kidney (HEK) 293T cells and harvested
      the cell lysates, and the cell lysates were then separated by SDS-PAGE and
      subjected to Western blot analysis 48 h after transfection. All four of the
      target proteins were detected in the cell lysates against the respective specific
      antibodies, suggesting that we have successfully constructed a eukaryotic vector
      co-expressing the four immunodominant antigens of Mycobacterium tuberculosis,
      which lay a foundation for the further study of the immunogenicity and protective
      activity of the four antigens.

PMID- 24941748
TI  - [Expression and bioactivity of OSF-1 in Pichia pastoris].
AB  - In order to research the biologic activity of osteoblast-stimulating factor 1
      (OSF-1), the pPIC9K/osf-1 yeast expression vector was constructed to express and
      purify OSF-1. Firstly, the osf-1 gene sequence was obtained by artificial
      synthesis and cloned into Pichia pastoris expression vector pPIC9K to generate
      pPIC9K/osf-1. The recombinant plasmid was linearized by Sac I and transformed
      into P. pastoris GS115 by electroporation. Recombinant P. pastoris GS115/
      pPIC9K/osf-1 was screened by MD and G418-YPD plates and further identified by
      PCR. The positive P. pastoris was induced with 1% methanol at 25 degrees C for 96
      h. The target protein was analyzed by SDS-PAGE showing a special band about 18
      kDa. The target protein was successfully purified from the supernatant of the
      broth using ion exchange chromatography of SP-Sephadex C-50. The purity of target
      protein was above 98%. Western blotting appeared a good antigenicity of the
      purified protein. Bioassay results show that the recombinant protein OSF-1 can
      promote the differentiation and proliferation of osteoblasts MC3T3-E1. We
      successfully expressed OSF-1 by recombinant P. pastoris for further development
      of anti-osteoporosis of research and industrial production of OSF-1.

PMID- 24941749
TI  - [A novel reporter system monitoring sortase A catalyzed protein ligation
      efficiency].
AB  - Efforts on directed evolution of sortase A to optimize its catalytic properties
      have been undertaken and shown the promise. To facilitate screening of sortase A
      mutants with expected catalytic properties, a novel ligation efficiency
      monitoring system, including reporter substrates GFP-LPETG and GGGYK-Biotin, was
      developed. GFP-LPETG, wild type sortase A, and a recently reported high activity
      sortase A mutant were prepared recombinantly from Escherichia coli BL21 (DE3).
      Taking advantage of the newly designed reporter system, the ligation efficiency
      catalyzed by wild type and mutant form of sortase A could be sensitively
      monitored via SDS-PAGE directly. Consistent with previous report, the mutant
      sortase A displayed much higher catalytic activity compared to wild type enzyme,
      indicating the new reporter system is easily and fast handled and sensitive. The
      application of this reporter system into systemic screening will facilitate
      future directed optimization of sortase A.

PMID- 24941750
TI  - [Comparison of metabolite extraction from Boea hygrometrica by gas
      chromatography/mass spectrometry].
AB  - This study is aiming to establish an efficient metabolite extraction method for
      exploration of molecular mechanisms of desiccation tolerance of the resurrection
      plant Boea hygrometrica using a metabolomics approach. The extracts of metabolite
      in B. hygrometrica using methanol solution (method A) and methanol-chloroform
      water solution (method B) were analyzed by gas chromatography-mass spectrometry
      (GC-MS). The total numbers of chromatographic peaks, extraction efficiency,
      retention time and the peak stability were compared. The results showed that for
      fresh materials, the total chromatographic peak number of method B is more than
      that of method A; the extraction efficiency of nine representative metabolites by
      method B is higher than that by method A; the comparison of 10 random
      chromatographic peaks revealed that the relative standard deviation (RSD) values
      of the retention time are less than 1% for both methods, whereas the RSD values
      of the extraction efficiency is different. The percentage of peaks that owned RSD
      values of the extraction efficiency higher than 10% is 50% for method A and 100%
      for method B. In addition, method B was also efficient for dry materials from B.
      hygrometrica. The number of chromatographic peaks, RSD value of retention time
      and extraction efficiency of dry materials was similar to that of fresh materials
      using method B, but decreased sharply using method A. Putting together, our study
      provided evidence that method B is an efficient extraction method for further
      analysis of metabolites from this resurrection species.

PMID- 24941751
TI  - [Effects of chemically modified sugarcane bagasse on butanol production by
      immobilized Clostridium acetobutylicum XY16].
AB  - Sugarcane bagasse modified by polyethylenimine (PEI) and glutaraldehyde (GA) was
      used as a carrier to immobilize Clostridium acetobutylicum XY16 in the process of
      butanol production. The effects of chemically modified sugarcane bagasse on batch
      and repeat-batch fermentations were investigated. Batch fermentation was
      conducted with an addition of 10 g/L modified sugarcane bagasse and 60 g/L
      glucose, resulting in a high solvent concentration of 21.67 g/L and productivity
      of 0.60 g/(L x h) with the treatment of 4 g/L PEI and 1 g/L GA. Compared to the
      fermentations by free cells and immobilized cells on unmodified sugarcane
      bagasse, the productivity increased 130.8% and 66.7%, respectively. The fibrous
      bed bioreactor also maintained a stable butanol production during repeat-batch
      fermentations, achieving a maximum productivity of 0.83 g/(L x h) with a high
      yield of 0.42 g/g.

PMID- 24941752
TI  - [Process development for continuous ethanol fermentation by the flocculating
      yeast under stillage backset conditions].
AB  - Propionic acid, a major inhibitor to yeast cells, was accumulated during
      continuous ethanol fermentation from corn meal hydrolysate by the flocculating
      yeast under stillage backset conditions. Based on its inhibition mechanism in
      yeast cells, strategies were developed for alleviating this effect. Firstly, high
      temperature processes such as medium sterilization generated more propionic acid,
      which should be avoided. Propionic acid was reduced significantly during ethanol
      fermentation without medium sterilization, and concentrations of biomass and
      ethanol increased by 59.3% and 7.4%, respectively. Secondly, the running time of
      stillage backset should be controlled so that propionic acid accumulated would be
      lower than its half inhibition concentration IC50 (40 mmol/L). Finally, because
      low pH augmented propionic acid inhibition in yeast cells, a higher pH of 5.5 was
      validated to be suitable for ethanol fermentation under the stillage backset
      condition.

PMID- 24941753
TI  - [Production of L(+)-tartaric acid by immobilized Rhizobium strain BK-20].
AB  - The cis-epoxysuccinate hydrolase (CESH) from Rhizobium strain BK-20 is the key
      enzyme for L(+)-tartaric acid production. To establish a highly efficient and
      stable production process, we first optimized the enzyme production from
      Rhizobium strain BK-20, and then developed an immobilized cell-culture process
      for sustained production of L(+)-tartaric acid. The enzyme activity of free cells
      reached (3 498.0 +/- 142.6) U/g, and increased by 643% after optimization. The
      enzyme activity of immobilized cells reached (2 817.2 +/- 226.7) U/g, under the
      optimal condition with sodium alginate as carrier, cell concentration at 10%
      (W/V) and gel concentration at 1.5% (W/V). The immobilized cells preserved high
      enzyme activity and normal structure after 10 repeated batches. The conversion
      rate of the substrate was more than 98%, indicating its excellent production
      stability.

PMID- 24941754
TI  - [Management of congenital median perineal cleft in children: a report of 7
      cases].
AB  - OBJECTIVE: To discuss the treatment and diagnosis of congenital median perineal
      cleft in children. METHODS: Between January 2009 to February 2013, 7 cases were
      diagnosed as congenital median perineal cleft according to the symptoms. Among
      them, 4 cases underwent surgery to correct cleft with double triangular perineal
      flaps. The other 3 cases with minor cleft did not receive surgery management.
      RESULTS: There is an median cleft from the perineum to the anus with mucosa on
      the cleft surface. Primary healing was achieved in all the four patients with
      satisfactory appearance. The patients were followed up for 1-4 years with almost
      normal perineal appearance. CONCLUSIONS: Congenital perineal median cleft can be
      diagnosed according to the symptoms. Double triangular perineal flaps can be
      effectively correct the cleft to attain normal perineal appearance.

PMID- 24941755
TI  - [The application of medpor and split-thickness skin graft in formation of
      cranioauricular sulcus during auricular reconstruction with Nagata method].
AB  - OBJECTIVE: To investigate the application of medpor and split-thickness skin
      graft in formation of cranioauricular sulcus during auricular reconstruction with
      Nagata method. METHODS: The first stage operation was fulfilled according to the
      Nagata two-stage method which involves fabrication and grafting of the costal
      cartilage framework. The second-stage ear elevation operation was undertaken 6
      months later to form the cranioauricular sulcus. Split-thickness skin was taken
      from temporal and accipital area. After releasing the auricular framework and
      transplanting C shaped medpor at the rear side of framework, the temporaparietal
      fascia flap was transferred to cover postauricular medpor and framework. Then the
      split-thickness skin graft was implant on the fascia surface. RESULTS: From July
      2010 to August 2012, 20 cases (22 ears) were treated. Partial necrosis of
      temporaparietal fascia flap and framework exposure happened in 1 case. Successful
      ear reconstruction was achieved in other cases with satisfactory cranioauricular
      sulcus during the follow-up period of 6-18 months (average, 13 months).
      CONCLUSIONS: The application of medpor and split-thickness skin graft in the ear
      elevation of Nagata method for auricular reconstruction for microtia can achieve
      satisfactory results. It not only avoids the obvious scar in the donor site due
      to harvesting full-thickness and intermediate-thickness skin, but also reduces
      chest trauma due to harvesting costal cartilage.

PMID- 24941756
TI  - [Immediate breast and nipple reconstruction with the latissimus dorsi
      myocutaneous flap].
AB  - OBJECTIVE: To investigate the feasibility of immediate breast and nipple-areola
      reconstruction after skin-sparing mastectomy. METHODS: 24 patients who received
      skin-sparing mastectomy underwent immediate breast reconstruction with or without
      breast implants. The nipple-areola complex is also reconstructed with the skin
      paddle of the latissimus dorsi flap in one stage. RESULTS: All the latissimus
      dorsi myocutaneous flaps survived completely. Partial necrosis happened in two
      reconstructed nipples which healed after dress changing. The follow-up period
      ranged from 6 to 12 months. 3 patients presented with capsular contracture (Baker
      I), with no necessary of surgical revision. The retraction rate of reconstructed
      nipples projection is 35.4% at 6 months postoperatively and 38.6% at 12 months
      postoperatively. 91.7% of patients were satisfied or very satisfied with the
      breast shape, while 83.3% were satisfied or very satisfied with the breast
      volume. All the patients considered the reconstructed nipple very good, while
      91.6% were satisfied with the nipple projection. 91.7% considered immediate
      nipple reconstruction to be very important, and 8.3% considered it to be
      important. 66.7% considered the new breast could replace the breast they had
      lost, and 8.3% considered that it could not. CONCLUSION: For skin-sparing
      mastectomy, immediate breast and nipple reconstruction can achieve good aesthetic
      results.

PMID- 24941757
TI  - [Clinical application of veno-arteriolization of finger lateral vein for
      repairing severed finger tips].
AB  - OBJECTIVE: To investigate effect of veno-arteriolization of finger lateral vein
      for repairing severed finger tips. METHODS: From March 2007 to April 2012, 20
      patients with severed finger tips were treated with veno-arteriolization of
      finger lateral vein after failure in anastomosing artery of finger over times.
      During operation, the dominant digital artery at proximal end and the dominant
      finger lateral vein at distal end was anastomosed as the blood supply, the non
      superiorty finger lateral vein was anastomosed as the blood drainage. RESULTS:
      All flaps survived completely and achieved primary healing. 18 patients were
      successfully followed up for 6 to 12 months with satisfactory appearance and nail
      growth. Finger pulp was plump with good flexibility. The average length of nail
      was (15.6 +/- 2.7) mm and the average motion of DIP joint was (62 +/- 4) degrees.
      The average two point discrimination was (4.6 +/- 0.3) mm and the average
      sensation measurement was S3+. CONCLUSION: The veno-arteriolization of finger
      lateral vein is a valuable method for repairing severed finger tips, which can
      promote nail growth, and restore fingers motion and sensation.

PMID- 24941758
TI  - [Reconstruction finger web with dorsal two wing-shaped flap for the treatment of
      congenital syndactyly].
AB  - OBJECTIVE: To explore the clinical effect of using dorsal two wing-shaped flap to
      reconstruct finger web for treatment of congenital syndactyly. METHODS: This
      technique has been used in 19 children with congenital syndactyly. At the dorsum,
      a flap with V-shaped tip and two wing-shaped pedicle were designed and was just
      sewed up with an anchor-shaped incision at the palm. The web was primarily
      reconstructed without skin graft at base of fingers. Distal end of fingers were
      separated by using serrated flap and were closed after removal of fatty tissue.
      At some cases with tight skin connection. The defect area at lateral and distal
      end of fingers was closed by small pieces of skin graft. RESULTS: All the webs
      were reconstructed primarily without skin graft at the base of fingers. 7 cases
      with tight skin connection had small pieces of skin graft at lateral and distal
      end of fingers. Primary healing was achieved in all cases. After 1 to 6 months of
      follow-up, both the appearance and function were satisfactory without conspicuous
      scar. The reconstructed finger webs were in normal depth and width. CONCLUSIONS:
      Primary web space can be achieved by dorsal two wing-shaped flap without skin
      graft at base of fingers. It is one of the best choices for treatment of
      congenital syndactyly.

PMID- 24941759
TI  - [Micro-plasma radio frequency treatment for facial post-burn hyperpigmentation].
AB  - OBJECTIVE: To observe the clinical effect of micro-plasma radio frequency
      treatment of facial post-burn hyperpigmentation. METHODS: From June 2012 to
      August 2013, a total of 25 cases with facial post-burn hyperpigmentation were
      treated with micro-plasma treatment for 3-5 times. The roller tip was used with
      setting of 60-90 watts and 3-4 passes were performed in different directions.
      Treatments were repeated at an interval of 8 weeks. RESULTS: All patients
      tolerated the pain. After treatment, the facial hyperpigmentation improved.
      Complete recovery was achieved in 4 cases; significant improvement in 11 cases;
      moderate in 7 cases and no effect in 3 cases. No hyperpigmentation,
      depigmentation and scar formation was observed. CONCLUSION: Micro-plasma radio
      frequency treatment is an ideal treatment for post-burn hyperpigmentation with
      lower side effect.

PMID- 24941760
TI  - [Primary reconstruction of skin avulsion injury on both feet].
AB  - OBJECTIVE: To investigate the therapeutic effect of primary reconstruction of
      skin avulsion injury with bilateral anterolateral thigh flaps combined with
      thorax umbilicus flap or latissimus dorsi flap. METHODS: From June 2005 to Aug.
      2011, 4 cases with skin avulsion injury on both feet were treated. The bilateral
      anterolateral thigh flaps, including with anterolateral thigh cutaneous nerves,
      were transferred to cover the feet plantar. The thorax umbilicus flap or
      latissimus dorsi flap were used to cover the feet dorsum. RESULTS: All the skin
      avulsion injury were reconstructed primarily. All the flaps survived completely
      with good cosmetic and functional results. The patients were followed up for 6
      months to 2 years with good sensory recovery (two point discrimination: 14-18
      mm). CONCLUSION: The skin avulsion injury on both feet can be primarily
      reconstructed by bilateral anterolateral thigh flaps combined with thorax
      umbilicus flap or latissimus dorsi flap.

PMID- 24941761
TI  - [Preliminary study on CASK/Id1 pathway in fibroblasts of human keloid].
AB  - OBJECTIVE: To verify the existence and significance of calcium/calmodulin
      dependent serine protein kinase/inhibitors of differentiation 1 (CASK/Id1)
      pathway in fibroblasts of human keloid. METHODS: Immunofluorescence laser was
      used to confirm CASK and Id1 protein expression and localization in fibroblasts
      of the keloid and normal skin. RT-PCR and Western-blot were adopted to analysis
      the CASK and Id1 expression and differences between keloid and normal skin
      fibroblasts. The natural combination of CASK and Id1 protein of keloid
      fibroblasts was tested by immunoprecipitation. RESULTS: CASK and Id1 protein
      expression were both found in fibroblast cells of keloid and normal skin under
      normal circumstances. Most of CASK and Id1 were distributed in the cytoplasm and
      nucleus of fibroblasts. The results of RT-PCR showed that the expression of CASK
      mRNA in the keloid group was 0.658 +/- 0.024, which was lower than that in the
      normal control group (1.076 +/- 0.008, t = 11.159, P < 0.05). The expression of
      Id1 mRNA was 0.497 +/- 0.014, which was higher than that in the normal control
      group (0.307 +/- 0.017, t = 15.148, P < 0.05). The results of Western-blot showed
      that the expression level for CASK protein in the keloid group was 0.057 +/-
      0.006, which was lower than that in the normal control group (0.168 +/- 0.012, t
      = 13.524, P < 0.05); the expression of Id1 protein was 0.812 +/- 0.035, which was
      higher than that in the normal control group (0.368 +/- 0.031, t = 16.356, P <
      0.05). The results of immunoprecipitation showed that Id1 could be detected in
      the CASK precipitate, while CASK also could be detected in the Id1 precipitate.
      There was a natural binding of CASK and Id1 in keloid fibroblasts. CONCLUSION:
      CASK/Id1 signal pathway may be existed and involved in the proliferation of
      keloid fibroblasts, which is related with the occurrence of keloid.

PMID- 24941762
TI  - [Effects of pyrroloquinoline quinine on oxidative stress-induced apoptosis of
      Schwann cells and its mechanism].
AB  - OBJECTIVE: To investigate the effects of Pyrroloquinoline quinine (PQQ) on
      hydrogen peroxide-induced apoptosis of Schwann cells (SCs) and its mechanism.
      METHODS: SCs were isolated and cultured in vitro, and identified by S-100
      immunofluorescence staining. The cultured SCs were divided into control group,
      hydrogen peroxide-treated group, hydrogen peroxide and PQQ treated groups. The
      intracellular superoxide dismutase (SOD) and malondialdehyde (MDA) content was
      detected; the apoptotic rate of SCs induced by hydrogen peroxide was determined
      by flow cytometry assay. The Hoechst33342 staining was used to detect the nuclear
      fragmentation and apoptotic nuclear condensation of SCs; the Rhodamine123
      staining was used to detect the changes of mitochondrial membrane potential in
      SCs, the Western blot analysis was used to detect the expression of Bcl-2 in
      hydrogen peroxide induced SCs. RESULTS: The SOD activity was significantly
      decreased and MDA level was increased in H2O2 induced SCs (P < 0.05), after
      addition of PQQ, the SOD content increased and MDA content decreased (P < 0.05).
      Flow cytometry results showed that the early apoptotic rate was 58.8% in H2O2
      induced SCs, which has significant difference compared with the control group (P
      < 0.05), after addition of 10, 50, 100 nmol/L PQQ, the apoptotic rates were
      reduced to 33.7%, 18.7%, 3.9% respectively, showing significantly different with
      injured group (P < 0.05). Hoechst 33342 staining showed that H2O2 induced SCs had
      typical morphological characteristics, such as uptake of nuclear chromatin,
      nuclear shrinkage, nuclear fragmentation phenomenon. The proportion of apoptotic
      cells after PQQ treatment reduced. Rhodamine staining results showed that the
      H2O2 induced mitochondrial membrane potential reduction in SCs, which was
      reversed by addition of PQQ. Western blot analysis showed that the expression of
      Bcl-2 was decreased in H2O2 induced SCs, while it increased significantly after
      addition of PQQ (P < 0.05). CONCLUSION: PQQ has a protective effect on oxidative
      stress-induced apoptosis of SCs.

PMID- 24941763
TI  - [Effects of botulinum toxin type A on the expression of alpha-SMA and myosin-II
      of fibroblasts in scars].
AB  - OBJECTIVE: To investigate the effects of botulinum toxin type A (BTXA) on the
      expression of alpha smooth muscle actin(alpha-SMA) and myosin-II of fibroblasts
      in scars. Methods Fibroblasts were isolated from tissue specimens of scars
      contracture. Cells from passages 3-5 were randomly divided into 3 groups (control
      group, low BTXA group (1 U/10(6) Cells), and high BTXA group (2.5 U/
      10(6)Cells)). Growth condition of fibroblasts was observed at 1 , 4, 7 day after
      BTXA treated. Changes of alpha-SMA and myosin-II in fibroblasts were detected by
      Western blot. RESULTS: Fibroblasts grew well in control group. The proliferation
      was decreased 4 days later in BTXA groups. Lots of apoptotic cells were seen in
      high BTXA group at 7th day. Proteins of alpha-SMA and myosin-II in fibroblasts
      were statistically different between BTXA group and control groups at 4th day (P
      < 0.05). The expression of alpha-SMA and myosin-II in low BTXA group was higher
      than that in high BTXA group at 7th day (P < 0.05). CONCLUSIONS: BTXA could
      induce the apoptosis of fibroblasts and decrease the expression of alpha-SMA and
      myosin-II in fibroblasts. The inhibitory effect was strengthened with BTXA
      concentration increase within a certain range.

PMID- 24941764
TI  - [Experimental study on removal melanin granules from acellular dermal matrix of
      giant nevus].
AB  - OBJECTIVE: To study the possibility of removal melanin granules from autogenic
      acellular dermal matrix of giant nevus tissue by H2O2 bleaching technique.
      METHODS: A total of 32 skin specimens (0.5 cm x 0.5 cm) from giant nevus tissue
      and 1 piece (0.5 cm x 0.5 cm) of normal skin were obtained from the surgical
      removal. One giant nevus tissue was chosen as control. The others and the normal
      skin tissue were treated with solution of 0.25% Dispase II for digestion for 24
      hours under normal temperature to remove epidermis. Then each piece was immerged
      into solution of 0.5% Triton X-100 for digestion for 48 hours in normal
      temperature. One giant nevus tissue and the normal skin tissue were chosen as
      control. The others were immerged into solution of different concentrations of
      H2O2, treated under different temperature and lasting for different period.
      Lastly, all specimens were treated with HE staining, immunohistochemical
      staining, light microscopy and so on. RESULTS: After giant nevus tissues were
      treated with solution of 0.25% Dispase II and immerged into solution of 0.5%
      Triton X-100 in normal temperature, nevus cells and all other cellular components
      of pigmented nevus tissues can be effectively removed, there were the cavities
      left by removal of cells without any residual cell debris, but still remaining
      part of pigment. Then each specimen were immerged into solution of different
      concentrations of H2O2, under different temperature and lasting for different
      period which can remove residual melanin granules. In solution of 3% H2O2 for 36
      h under 37 degrees C, can remove all the melanin particles, the content of
      collagen type I in the obtained specimen was not changed. Collagen fibers were
      uniform in thickness, regular in arrangement with no obvious degeneration.
      CONCLUSIONS: With solution of 0.25% Dispase II and solution of 0.5% Triton X-100
      in normal temperature, all cells in nevus tissue can be removed effectively.
      Further treatment with 3% H2O2 at 37 degrees C for 36 h can remove all the
      melanin particles, while collagen type I has no obvious change. The preparation
      of acellular dermal matrix of the giant nevus may possibly be applied as
      autologous tissue implant to repair tissue defects.

PMID- 24941765
TI  - [Clinical anatomic study of Pitanguy ligament of the nose].
AB  - OBJECTIVE: To observe the origins and insertions of Pitanguy ligament,in order to
      find the anatomically theoretical basis for the treatment of nasal deformity such
      as drooping nose, short columella, gingival show. METHODS: 15 cadaveric heads
      fixed by 10% formalin were used. 12 specimens underwent nasal anatomic study. The
      skin was incised, along the nasal midline to expose the Pitanguy ligament. The
      origin of Pitanguy ligament and its relationship with surrounding tissue were
      studied. Then the Pitanguy ligament was taken out for HE staining. Longitudinal
      section along the ligament was observed. 3 specimens underwent harvesting of full
      thickness nasal tissue from skin to periosteal membrane. Then the samples were
      used for HE staining to show histologic study of ligament at horizontal section.
      RESULTS: Pitanguy ligament originates in the midline of lower third of the nasal
      superficial musculoaponeurotic system, extends down to the tip along the midline
      of the nasal dorsum and then turns backwards at the nasal tip, and runs between
      the medial crura of the lower lateral cartilages, inserts into the base of
      columella. Its muscle is connected with the orbicularis oris muscle and the
      depressor septi nasi muscle. HE staining showed the ligament consists of fibrous
      connective tissue, muscle tissue and other ingredients, but without cartilage.
      CONCLUSIONS: Pitanguy ligament exists with complex histological composition, so
      its name is still controversial. Because it has multiple connection with the
      orbicularis oris muscle and the depressor septi nasi muscle, so cutting or
      shortened the Pitanguy ligament can treat deformity of nose and lip by adjustment
      of nasolabial angles and the nasal length.

PMID- 24941766
TI  - [Development of skin moisture and body fat measurement system for mobile
      application].
AB  - Integrating physiological parameters measurement into mobile devices is a
      development tendency of mobile healthcare. Measurement methods for skin moisture
      and body fat content are studied in this paper. Electrodes are designed for easy
      integration into mobile devices, and can be embedded in the cover of the mobile
      phone. Experiments were conducted to obtain a fast and easy measurement method.
      The results of evaluation show that the measurement system can achieve the same
      accuracy as commercial products (with correlation above 0.9 and root mean squared
      error below 4%) in skin moisture and body fat content measurement. Measurement of
      local-area body fat content showed a nearly linear positive correlation between
      local-area body fat content and local-area body impedance.

PMID- 24941767
TI  - [3D-TV health assessment system by the multi-modal physiological signals].
AB  - In order to meet the requirements of the multi-physiological signal measurement
      of the 3D-TV health assessment, try to find the suitable biological acquisition
      chips and design the hardware system which can detect different physiological
      signals in real time. The systems mainly uses ARM11/S3C6410 microcontroller to
      control the EEG/EOG acquisition chip RHA2116 and the ECG acquisition chip
      ADS1298, and then the microcontroller transfer the data collected by the chips to
      the PC software by the USB port which can display and save the experimental data
      in real time, then use the Matlab software for further processing of the data,
      finally make a final health assessment. In the meantime, for the different
      varieties in the different brain regions of watching 3D-TV, developed the special
      brain electrode placement and the experimental data processing methods, then
      effectively disposed the multi-signal data in the multilevel.

PMID- 24941768
TI  - [Optimization of electrode location and size on simulation in electric field
      distribution of atrial defibrillation].
AB  - A distributed simulation method of electric field based on the atrial
      defibrillation of the heart modeling and finite element solution is proposed in
      this study. In order to solve the problem that ordinary clinical trials could not
      measure the actual distribution of the defibrillation electric field in the heart
      accurately, this method provides a research tool for electrical defibrillation. A
      complete atrial anatomical structure in the heart model is used in the research,
      the finite element method is proceeded to solve; Three parameters: defibrillation
      threshold voltage, the high field strength rate and the defibrillation threshold
      energy are set to evaluate the effect of defibrillation. The heart electric field
      distributions of transvenous atrial defibrillation with different electrode
      locations or sizes are simulated. The simulation results and the reported results
      match fairly well, which initially verify the feasibility of this method.

PMID- 24941769
TI  - [Automated segmentation of retina layer structures on optical coherence
      tomography].
AB  - OBJECTIVE: Using the algorithm on the layered structure of the retina and
      quantitative analysis of the automatic segmentation technique is the key to the
      early diagnosis of glaucoma and other retinopathy on optical coherence
      tomography. Existing methods require high quality image and have low reliability.
      This paper used the improved complex nonlinear diffuse filtering and other
      methods to solve this problem. METHODS: This paper includes algorithm such as
      automatic threshold, improved complex nonlinear diffusion filtering,
      morphological operations and peak detection. Use the method for the segmentation
      of 20 retinal layers images which acquired on the self-builder OCT system, the
      boundary of inner limiting membrane(ILM), outer nuclear layer(ONL), the
      photoreceptor segments(IS/ OS) and the RPE_ChCap layer are detected accurately.
      At last, the photoreceptor layer thickness is measured. RESULTS: The results of
      segmentation and measurement are good corresponded with expert manual
      segmentation and measurements, retinal foveal measurements data is consistent
      with Zeiss Stratus OCT central retinal thickness 212+/-20 micro m. CONCLUSION:
      The algorithm proposed is prospective applied to clinical diagnosis of retinal
      diseases.

PMID- 24941770
TI  - [Optimization based on finite element technique of nitinol stent].
AB  - The finite element method was used for simulating the mechanical performance and
      fatigue safety of three different structures of Nitinol stent. According to the
      actual situation, after proposing reasonable assumptions and simplification, the
      geometry model and finite element model establishment, material mode selection
      and boundary condition setting are completed. The strain and fatigue life of
      different stent edges wide (omega) or strut angle (theta) are computed. The
      result can provide a valuable reference for the optimal design of stent.

PMID- 24941771
TI  - [CW bio-radar vital sign detector and experiment study].
AB  - Non-contact vital sign detection technique provides an effective usage in health
      monitoring applications. A vital sign detector was designed based on microwave
      bio-radar technique. Using Doppler principle, continuous wave bioradar was
      designed for tiny body movement detection, short-time Fourier transform and
      interpolation algorithm were adopted for heart and respiration rate extraction,
      embedded system was used for system integration, real-time signal processing
      software was designed on it. Experiments were done by using simulation device and
      human body for research and performance evaluation. The result shows that the
      proposed prototype can be used for single target vital signs detection at the
      distance of 90 cm, and the heart rate result shows a 96% recognition rate.

PMID- 24941772
TI  - [The development of the system of blood flow block by using magnetic compression
      abdominal large vascular].
AB  - A new system of blood flow block for control of bleeding in abdominal operation
      is composed of an abdominal magnetic blocking unit, an abdominal external
      electromagnet unit and other non-magnetic operation instrument. The abdominal
      external electromagnetic unit is placed in advance in the operation bed. The
      abdominal magnetic blocking unit can be placed directly on the ventral of the
      large vessels when need to blocking the abdominal large vessels during the
      operation. According to the non-contact suction characteristics of magnetic
      materials, the two magnetic units will attract each other and compression the
      vessels. Using this system for vascular occlusion does not need clear exposure
      and without separating vessel. There is the advantage of rapid, accurate and
      reliable for the system.

PMID- 24941773
TI  - [Design of mobile vital-signs monitoring system for the elderly in nursing home].
AB  - This paper proposed a mobile vital-signs monitoring system based on ZigBee
      localization and wireless transmission technology for the elderly in nursing
      home. The system can monitor the vital-signs (pulse, ECG and blood oxygen),
      localize human body and warn in emergency. The validity and accuracy of this
      system were testified by the experiments of mobile acquisition and storage of
      pulse. In these experiments, the measurement of pulse ranged from 50 to 170 time
      a minute, the mean error of which was less than 3%. The mean error of localizing
      was less than 4 m. And the data transmission rate was 250 kbps. The system, which
      effectively conducts the real-time monitoring of the health and safety situation
      for the elderly, has a great significance for protecting the elderly's life
      safety.

PMID- 24941774
TI  - [Development of automatic urine monitoring system].
AB  - An automatic urine monitoring system is presented to replace manual operation.
      The system is composed of the flow sensor, MSP430f149 single chip microcomputer,
      human-computer interaction module, LCD module, clock module and memory module.
      The signal of urine volume is captured when the urine flows through the flow
      sensor and then displayed on the LCD after data processing. The experiment
      results suggest that the design of the monitor provides a high stability,
      accurate measurement and good real-time, and meets the demand of the clinical
      application.

PMID- 24941775
TI  - [Phantom holder of CT couch].
AB  - This article describes a phantom holder in CT couch which adjusted easily and
      accurately, installed easily. The holder mainly include removing and locking
      equipment between phantom holder and table top, move horizontally equipment
      between left and right, rotating equipment between left and right. After holder
      and table top fixed one part, holder with phantom can move horizontally, front
      and back, rotate between left and right in a small angle, in order to make
      operator test phantoms accurately and easily. At the same time, this phantom
      holder realized free adjustment after first adjustments, which shortened operator
      work time.

PMID- 24941776
TI  - [Application of nanomaterials in in-vitro diagnostics].
AB  - Nanomaterials appear to be promising for a number of applications in in-vitro
      diagnostics, mainly due to the biocompatibility, specific surface and conduction
      activity. The use of nanostructures as diagnostic tools has the advantage of very
      low limit of detection achievable, high sensitivity, strong selectivity and the
      possibility to fabricate point-of-care diagnostic devices. With the problems of
      nanotechnology solved, nanomaterials had already put a broad impact in the field
      of clinical medical examination.

PMID- 24941777
TI  - [Research of ultrasound biomicroscopy in ophthalmology].
AB  - Ultrasound biomicroscopy (UBM) has been applied in ophthalmology for twenty
      years. It plays an important role in diagnosis of eye diseases, especially in
      glaucoma. After years of research, It has been developed in its structure,
      sensors, imaging technology and applied research.

PMID- 24941778
TI  - [Particle evaluation of cardiovascular stents].
AB  - This paper has briefly introduced the definition, classification, harms, sources
      and control of particles, lists the particle evaluation method of coronary
      stents. And the development trend of particle evaluation method of coronary
      stents is also analyzed.

PMID- 24941779
TI  - [Comparative study of medical device classification between China and USA].
AB  - This paper introduced the medical device classification in China and USA. Through
      the comparison between the two systems, several problems in Chinese
      classification system were exposed. To the end, some suggestions were proposed
      referred to the classification system of USA.

PMID- 24941780
TI  - [Analysis of the common problems of standards during medical devices
      registration].
AB  - According to the registered product standards specification of medical devices,
      combined with the standard reviewing work, the common problems of standards
      during medical devices registration were analyzed and corresponding suggestions
      were proposed to standardize the standard of the registered product, accelerate
      the standardization and promote the industry standardized.

PMID- 24941781
TI  - [Evaluation methods of HME with tracheostomized patients].
AB  - This paper introduced the measurement methods of heat and moisture exchanger
      during tracheotomy with two main parameters (water loss and pressure drop) and
      proposed more heat and moisture exchanger evaluation indicators such as the death
      chamber, the heat exchange rate, as well as those parameters can be used to
      evaluate the reasonableness of the heat and moisture exchanger performance.

PMID- 24941782
TI  - [Introduction to method for determination of bio-burden on surgical drapes, gowns
      and clean air suits].
AB  - Firstly, the essay introduces the definition of bio-burden, the significance of
      determination of bio-burden and the specific performance requirements. Then, the
      essay introduces the method selection and validation on the bio-burden
      determination of surgical drapes, gowns and clean air suits.

PMID- 24941783
TI  - [Use of megavoltage CT(MVCT) in helical tomotherapy for head and neck dose
      calculation].
AB  - OBJECTIVE: To evaluate the feasibility and accuracy of using Megavoltage CT(MVCT)
      for head and neck dose calculation. METHODS: The cheese Phantom was imaged using
      MVCT scanner, and the MVCT value density calibration curve was established.
      Conventional CT and MVCT image of nasopharyngeal carcinoma was acquired
      respectively, and IMRT plan was designed on conventional CT image of NPC patient.
      The conventional CT plan was copied to MVCT image. The dose distribution was
      calculated for tumor and normal tissue using the MVCT value density calibration
      curve, and compared with that of conventional CT. Ten NPC patients were collected
      for dose verification of IMRT plan on MVCT images. RESULTS: The MVCT numbers
      depended linearly on the electron density of the sample, and the stability of the
      MVCT numbers to electron density was good.The error between the measured dose and
      calculated dose in measured point was less than 3%.The isodose distribution was
      well agreement with that calculated by planning system. CONCLUSIONS: Performing
      dose recalculation using MVCT of Tomotherapy in head and neck region was
      feasible.and the dose distributions on kVCT and MVCT were in excellent agreement.

PMID- 24941784
TI  - [Design of medical devices management system supporting full life-cycle process
      management].
AB  - Based on the analysis of the present status of medical devices management, this
      paper optimized management process, developed a medical devices management system
      with Web technologies. With information technology to dynamic master the use of
      state of the entire life-cycle of medical devices. Through the closed-loop
      management with pre-event budget, mid-event control and after-event analysis,
      improved the delicacy management level of medical devices, optimized asset
      allocation, promoted positive operation of devices.

PMID- 24941785
TI  - [Practice and exploration of medical equipment's preventive maintenance based on
      risk analysis].
AB  - This paper analyzes the characteristics of medical equipment's preventive
      maintenance, and it expounds the objective and methods of introducing risk
      management to medical equipment's preventive maintenance,what's more,the problem
      of establishment object and cycle of preventive maintenance was solved
      scientifically.

PMID- 24941786
TI  - [Method and application for improving the load capacity of CT diagnosis table
      top].
AB  - In the load capacity test of CT diagnosis table top, by analyzing the easy
      destroy area and related test data for the table top, using a simple mechanical
      auxiliary support structure in local area of the table top to solve the
      insufficient loading strength problem of table top and obtain significant results
      during the actual product usage.

PMID- 24941787
TI  - [The significance of ambulance equipped with ventilation in transportation of
      patients with cerebral infarction and OSAHS].
AB  - During transportation of patients with cerebral infarction and OSAHS, 54 Patients
      in comparison group was not in the ambulance with ventilator while 73 patients in
      observation group with ventilation. After two weeks treatment, the observation
      group's heart rate, systolic blood pressure, diastolic blood pressure and carbon
      dioxide partial pressure were significantly lower than that of the comparison
      group, while the oxygen partial pressure and oxygen saturation was significantly
      higher than the comparison group,observation group mortality rate was 2.74%,
      significantly lower than the comparison group which was 7.41%.

PMID- 24941788
TI  - Introduction: science, technology, medicine--and the state: the science-state
      nexus in Scandinavia, 1850-1980.

PMID- 24941789
TI  - From administrative infrastructure to biomedical resource: Danish population
      registries, the "Scandinavian laboratory," and the "epidemiologist's dream".

PMID- 24941790
TI  - Producing standards, producing the Nordic region: antibiotic susceptibility
      testing, from 1950-1970.

PMID- 24941791
TI  - United in separation: the inventions of gel filtration and the moral economy of
      research in Swedish biochemistry, ca. 1950-1970.

PMID- 24941792
TI  - Circumpolar science: Scandinavian approaches to the Arctic and the North
      Atlantic, ca. 1920 to 1960.

PMID- 24941793
TI  - Versions of milk and versions of care: the emergence of mother's milk as an
      interested object and medicine as a form of dispassionate care.

PMID- 24941794
TI  - Building transnational bodies: Norway and the International Development of
      Laboratory Animal Science, ca. 1956-1980.

PMID- 24941795
TI  - Inventing Homo gardarensis: prestige, pressure, and human evolution in interwar
      Scandinavia.
AB  - In the 1920s there were still very few fossil human remains to support an
      evolutionary explanation of human origins. Nonetheless, evolution as an
      explanatory framework was widely accepted. This led to a search for ancestors in
      several continents with fierce international competition. With so little fossil
      evidence available and the idea of a Missing Link as a crucial piece of evidence
      in human evolution still intact, many actors participated in the scientific race
      to identify the human ancestor. The curious case of Homo gardarensis serves as an
      example of how personal ambitions and national pride were deeply interconnected
      as scientific concerns were sometimes slighted in interwar palaeoanthropology.

PMID- 24941797
TI  - [Construction of shRNA expressing plasmid targeted rat NogoB and observation of
      the effection about NogoB on hepatic stellate cells].
AB  - OBJECTIVE: To construct shRNA expressing plasmid inhibiting rat NogoB and to
      observe its possible effect on rat primary hepatic stellate cells (HSCs)
      contraction. METHODS: Three pairs of shRNAs targeting different sequence of rat
      NogoB were designed and constructed into pSuper plasmid by DNA recombination
      technique. Culture-activated HSCs were transfected with NogoB-shRNA plasmids to
      scan the effective plasmid which could inhibit NogoB gene expression by Real-time
      PCR. And this depressant effect was also confirmed with Western blot. After NogoB
      was knocked-down effectively, ETA and ETB mRNA expression were assessed by Real
      time PCR. RESULTS: Among the three pairs of recombinant plasmids, NogoB-shRNA2
      plasmid could inhibit NogoB expression specifically. In HSCs, NogoB knockdown
      decreased the ratio of ETA and ETB. CONCLUSION: We constructed specific NogoB
      shRNA expression plasmid successfully which might be involved in contraction of
      HSCs.

PMID- 24941796
TI  - [Synergistic effect of targeted inhibition of MEK/ERK and PI3K/AKT survival
      signaling pathways on induction of apoptosis in melanoma].
AB  - OBJECTIVE: The treatment of metastatic melanoma by conventional chemotherapeutic
      agents remains unsatisfactory. The present study was undertaken to reveal the
      role of co-inhibition of survival signaling pathways in apoptosis of melanoma
      cells. METHODS: A panel of human melanoma cell lines and fresh melanoma isolates
      was assessed for their sensitivity to the MEK inhibitor U0126 and/or AKT
      inhibitor LY294002. The proliferation and apoptosis of the cells were examined
      after treatment with the inhibitors. RESULTS: Constitutive activation of ERK1/2
      and AKT was closely related to concentrations of serum in the culture medium
      (extracellular signals). The sensitivity of melanoma cells to apoptosis induced
      by inhibition of MEK/ERK was not correlated with the active BRAF mutation
      (BRAF(V600E)). Inhibition of MEK/ERK predominantly induced apoptosis; whereas
      inhibition of PI3K/AKT primarily inhibited proliferation. Co-inhibition of
      MEK/ERK1/2 and PI3K/AKT synergistically induced apoptosis. CONCLUSION: Co
      targeting MEK/ERK and PI3K/AKT pathways may further improve treatment for
      melanoma.

PMID- 24941798
TI  - [The research on the construction and characteristics of recombinant engineering
      bacteria with multi-epitope of Helicobacter pylori].
AB  - OBJECTIVE: To construct the multi epitope prokaryotic expression plasmid and
      appropriate engineering bacteria expressing the multi-epitope fusion protein of
      urea membrane channel protein (UreI), urease B subunit (UreB) and adhesin (HpaA)
      of Helicobacter pylori, then study its microbiological characteristics. METHODS:
      The target sequence contains multi epitope gene sequence of Helicobacter pylori
      were designed and synthesized, subsequently; it was subcloned into the expression
      vector pET28a (+), confirmed by restriction enzyme digestion and DNA sequencing.
      The fusion protein rIBA was expressed in E. coli Rosseta (DE3) and analyzed by
      Western blot. RESULTS: The plasmid of pET28a(+)/IBA was constructed successfully,
      confirmed by endonuclease digestion and sequence analyze. The expressed rIBA
      protein with relative molecular mass about 40 x 10(3) and can be detected by
      Western blot. CONCLUSION: The prokaryotic engineering bacteria expression multi
      epitope of the Helicobacter pylori was constructed successfully. The recombinant
      protein rIBA expressed by the engineering bacteria can be identified by Sydney
      strain 1 of Helicobacter pylori (H. pylori SS1) specific antibody IgY, which
      demonstrated that the rIBA has high correlation with H. pylori SS1.

PMID- 24941799
TI  - [The mechanism of ciclosporin A regulating the expression of LOX-1 on vascular
      endothelium of hyperlipidemic rats].
AB  - OBJECTIVE: To observe the influence of Ciclosporin A (CsA) on the expression of
      lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1) on
      vascular endothelium of hyperlipidemic rats. METHODS: Hyperlipidemic rats model
      as for the study objects firstly were established. Then the high [5 mg/(kg x d)]
      and low [1 mg/(kg x d] dose of CsA were used to stimulate these rats, while the
      rats of normal blood lipids as control. After the end of intervention, the
      protein expressions of LOX-1 and C-reactive protein (CRP) on vascular endothelium
      of thoracic aorta were observed by Western blot and immunohistochemistry
      respectively. The serum levels of ox-LDL and reactive oxygen species (ROS) were
      also examined. RESULTS: An obviously up-regulated expression of LOX-1 on vascular
      endothelium of hyperlipidemic rats treated with CsA was observed (P < 0.05), but
      not the serum level of ox-LDL (P > 0.05). The further study result implied that
      CsA could increase the expression of CRP on vascular endothelial cells and serum
      level of ROS (P<0. 05). CONCLUSION: CsA can significantly upregulate the
      expression of LOX-1 on vascular endothelium of hyperlipidemic rats through not
      only ox-LDL/LOX-1 pathway but also ROS/CRP pathway, which could cause the
      probability of occurrence of atherosclerosis.

PMID- 24941800
TI  - [Diammonium glycyrrhizinate promotes aquaporin-5 in LPS-induced acute lung injury
      via inactivation of NF-kappaB].
AB  - OBJECTIVE: To determine the therapeutic value and associated mechanism of
      diammonium glycyrrhizinate (DG) on the expression of AQP-5 in
      lipapolysacchairides (LPS)-induced acute lung injury in mice. METHODS: Thirty
      male BALB/c mice were randomly divided into three groups equally: Control, LPS+DG
      and LPS. HE staining and lung injury score system were used to evaluate the
      pathological changes in the lung tissues. Wet to dry ratio (W/D) was used to
      measure the degree of lung edema. RT-PCR and Western blot were obtained to
      measure AQP-5 expression. Total NF-kappaB p65 and phospho-NF-kappaB p65 (p-NF
      kappaB p65) were evaluated by Western blot. RESULTS: After 3 days of LPS
      intratracheal injection, severe pathological changes, increased W/D, down
      regulated AQP-5 expression and increased p-NF-kappaB p65/total NF-kappaB p65 were
      observed. Compared with mice in the LPS group, mice in the LPS+DG group had more
      significantly ameliorated pathological changes and increased W/ D, up-regulated
      AQP-5 expression, and reduced p-NF-kappaB p65/total NF-kappaB p65. CONCLUSION: DG
      up-regulates AQP-5 in vivo, possibly resulting from inactivation of NF-kappaB.

PMID- 24941801
TI  - [High glucose induces sumoylation of Smad4 via SUMO2/3 in glomerular mesangial
      cells].
AB  - OBJECTIVE: To investigate the expression of SUMO2/3 and Smad4 in rat glomerular
      mesangial cells (GMCs) induced by high glucose, and the interaction between small
      ubiquitin related modifier (SUMO)2/3 and Smad4; and to explore the role and
      mechanism of sumoylation in regulating TGF-p signaling in diabetic nephropathy.
      METHODS: Cultured rat GMCs were divided into five groups: normal glucose group
      (5. 6 mmol/L glucose), high glucose groups (10, 20 and 30 mmol/L glucose), and
      mannitol group (osmotic control). The expression of SUMO2/3, Smad4 and
      fibronectin (FN) was measured by Western blot and RT-PCR. The interaction and
      colocalization between SUMO2/3 and Smad4 were detected by Co-immunoprecipitation
      and immunofluorescence confocal laser microscopy. RESULTS: Compared with
      controls, the expressions of SUMO2/3, Smad4 and FN in the cells in the high
      glucose groups increased (P < 0.05). The co-immunoprecipitation and
      immunofluorescence confocal laser scanning showed that Smad4 interacted and
      colocalized with SUMO2/3 and the sumolyation (SUMO2/3) of Smad4 was enhanced
      significantly in the high glucose groups compared with the control group (P <
      0.05). CONCLUSION: Sumolyation of Samd4 by SUMO2/3 may be involved in the
      regulation of TGF-beta signaling in diabetic nephropathy.

PMID- 24941802
TI  - [Changes on the expression of aquaporin-4 is associated with edema of brain in
      neonatal rats subjected to hypoxic ischemic brain damage].
AB  - OBJECTIVE: To investigate changes of Aquaporin-4 (AQP-4) and the relation of
      brain edema after different time of hypoxic ischemic brain damage (HIBD).
      METHODS: Healthy 3 day-old SD rats (n=60), were divided into Sham group (n=12),
      the hypoxic ischemic brain damage group (n=48). The rats were subjected to the
      ligation of right carotid artery (ischemia). After rewarming 30 min with mother,
      they were sent into a box full with 80 mL/L oxygen and 920 mL/L nitrogen
      (hypoxia) for 4 h, 8 h, 16 h, 24 h (n=12 respectively). The rats of sham group
      were subjected to exposure right carotid artery, but were not ligated. Rats of
      the HIBD group were sacrificed at 4 h, 8 h, 16 h, 24 h of hypoxic ischemic damage
      and rats of the sham group were sacrificed at 12 h after operation without
      hypoxic ischemic damage. Then brain water content from left and right hemisphere
      were investigated respetively to observe brain edema at different time of hypoxic
      ischemic brain damage, which was followed by the investigation of brain pathology
      through HE staining. Real time PCR was used to test the level of AQP-4 mRNA.
      RESULTS: Water content of right brain increased significantly after 8 h, 16 h and
      24 h hypoxic ischemic brain damage, compared with the sham group (P < 0.05).
      Under light microscopy, the size of neurons and glia cells increased gradually
      during 8-24 h following HIBD. Dissolved Neurons were obviously observed during 16
      24 h of HIBD. Glia cells were scarcely distributed. The mRNA expression of AQP-4
      in right hippocampus decreased significantly during 4-24h of HIBD by evaluated
      with real time PCR (P < 0.05), when compared with the sham group. CONCLUSION: AQP
      4 mRNA expression in hippocampus of neonatal rats with HIBD exhibited a
      significant decrease, which was associated with brain edema. The present findings
      indicated that AQP-4 may has a novel role in the brain edema in neonatal rats
      with HIBD.

PMID- 24941803
TI  - [Construction of recombinant over expression vector of PENK gene and the function
      study of PENK gene].
AB  - OBJECTIVE: To construct recombinant over expression vector of Homo sapiens
      proenkephalin (PENK) gene and explore the function of PENK gene. METHODS:
      Fragment containing PENK ORF gene was inserted into vector plasmid HIV, then the
      recombinant over was confirmed by enzyme digestion and sequencing. Lentivirus
      containing the recombinant over expression vector was produced by virus packaging
      with 293Ta cell,and then the lentivirus was transfected into HT1080 cell and the
      virus titer was estimated. The PC12 were tansfected with resulting lentivirus and
      un-transfected PC12 cells as control. The images of the PC12 cells were captured
      at 48 h post-transfection and the number of cells was also evaluated; the changes
      of PENK mRNA in transfection and control group were measured with RT-PCR.
      RESULTS: The constructed PENK ORF recombinant over expression vector was
      confirmed by enzyme digestion and sequencing. The number of PC12 cells in
      transfection and control group at 48 h post-transfection was 127.93 +/- 2.48 and
      88. 60 +/- 2.55 respectively, and the statistical difference between them was
      observed (P < 0.01). CONCLUSION: Recombinant over expression vector of PENK gene
      was successfully constructed and the PENK gene can promote the growth of PC12.

PMID- 24941804
TI  - [Expression and significance of BNIP3 in clear cell renal cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of proapoptosis protein BNIP3 in clear
      cell renal cell carcinoma (ccRCC) and its clinical significance. METHODS: The RCC
      tumor tissue samples from 30 pathologically diagnosed ccRCC and their adjacent
      pericarcinous tissues were adopted to detect the mRNA and protein expressions of
      BNIP3, von Hippel-Lindau (VHL), hypoxia inducible factor (HIF)-1alpha and
      vascular enothelial growth factor (VEGF) by real-time quantitative PCR (real-time
      PCR) and Western blot. The correlations of these genes expressions with
      clinicopathologic features were analyzed. RESULTS: The expression levels of BNIP3
      and VHL were lower in ccRCC tissues than those in pericarcinous tissues (P <
      0.05), but the mRNA expression levels of HiF-1alpha and VEGF were higher in ccRCC
      tissues than those in pericarcinous tissues (P < 0.05). The lower level
      expression of BNIP3 in ccRCC was not related with any clinicopathologic features.
      No significant correlation was observed between the BNIP3 mRNA and protein level
      with the expressions of VHL, HIF-1alpha and VEGF. CONCLUSION: In ccRCC, the
      expression of BNIP3 is decreased, which not correlated with the expression levels
      of VHL, HIF-1alpha and VEGF.

PMID- 24941805
TI  - [Effects of thymosin alpha1 on immune effector molecules of mouse].
AB  - OBJECTIVE: To analysis the effects of Talpha1 on the immune effector molecules in
      mouse immune system. METHODS: Sixty five BABL/c mice were divided into four
      groups: CsA group (n=20), Talpha1 group (n= 20), CsA+Talpha1 group (n=20) and
      control group (n=5). In the 3 experimental groups, 10 mg/kg CsA, 400 microg/ kg
      Talpha1, 10 mg/kg CsA+400 microg/kg Talpha1 were respectively administrated by
      intraperitoneal injection daily. Luminex was performed for cytokine detection at
      1 d, 7 d, 14 d, 21 d day after the above treatments. Lymphocyte culture was
      prepared with the mouse spleen suspension, and then treated with 0. 25 mg/mL CsA,
      10 microg/mL Talpha1 or 0.25 mg/mL CsA+10 microg/mL Talpha1 in vitro,
      respectively. Three days later, OD values of each treated lymphocyte culture and
      several cytokines in the culture were measured. RESULTS: Compared with other
      groups, CsA+Talpha1 group had significant lower IL-1alpha, IL-2, IL-6, IL-17, and
      significant higher IL-10 at 1 d, 7 d, 14 d, 21 d after the treatments (P < 0.05).
      Three days after the culture, OD value in the control group was significantly
      higher than that in Talppha1 group, CsA group, and CsA+ Talpha1 group (P < 0.05).
      IL-1alpa and IL-6 in the control group were significantly higher than those in
      the experiment groups (P < 0.05), while IL-10 in the control group was
      significantly lower than that in the experiment groups (P < 0.05). IL-2 and IL-17
      were similar. CONCLUSION: Talpha1 show regulatory effect on the immune effector
      molecules which could promote Th1 cells transforming to Th2 cells.

PMID- 24941806
TI  - [Expression of Chemokine receptor CXCR6 and its significance in breast cancer
      cell lines].
AB  - OBJECTIVE: To detect the expression of Chemokine receptor CXCR6 in invasive
      breast cancer cell lines and normal mammary epithelial cell line, and assess the
      relationship between CXCR6 expression and malignant behavior of breast cancer
      cells. METHODS: Expression level of CXCR6 in different invasive breast cancer
      cell lines (SK-BR-3, MCF-7, MDA-MB-231) and normal mammary epithelial cell line
      (MCF-10A)was detected by real time reverse transcription-polymerase chain
      reaction (real time-PCR) and Western blot. Lentivirus was employed to interfere
      CXCR6 expression in MDA-MB-231. MTT assay and transwell chamber were used to
      study proliferative and invasive ability of those cells respectively. Vascular
      enothelial growth factor (VEGF) expression was detected to study the role of
      CXCR6 in angiogenesis. RESULTS: At both mRNA level and protein level, normal
      mammary epithelial cell line MCF-10A showed the weakest CXCR6 expression. The
      breast cancer cell lines expressed CXCR6 in different levels, the expression
      level of CXCR6 in highly invasive cell line MDA-MB-231 was significantly higher
      than that in two low-invasive cell lines SK-BR-3 and MCF-7 (P < 0.05). Silencing
      CXCR6 gene by Lentivirus-mediated RNA interference in MDA-MB-231 inhibited its
      proliferation ability, invasion ability and angiogenesis ability in vitro (P <
      0.05). CONCLUSION: Different invasive breast cancer cell lines express CXCR6 at
      different levels, positively correlated with its invasive ability.

PMID- 24941807
TI  - [Effect of tanshinone II A on leukemia cell line K562].
AB  - OBJECTIVE: To determine the anti-proliferative effect of Tanshinone II A (TAT) on
      leukemia K562 cell line and its mechanism. METHODS: The proliferation of K562
      cell line was detected by MTT assay. The morphological changes of the cells were
      examined with light microscope. The cell apoptosis was detected by flow
      cytometry. The expressions of BCL-2, BAX and m-TOR signaling pathway were
      examined by Western blot assay. RESULTS: TAT inhibited the proliferation of K562
      cell line, with a value of IC50 (7.75 +/- 2.47) micromol/L after treatment for 96
      h. Significant morphological changes were found after incubation of the cells for
      24 h. The apoptotic rate accelerated after TAT treatment for 24 h compared with
      the controls. TAT down-regulated the expression of mTOR signaling pathway and BCL
      2 protein, and up-regulated proapoptotic protein BAX. CONCLUSION: TAT can inhibit
      the proliferation of K562 cells through down-regulating mTOR signaling pathway,
      inducing apoptosis.

PMID- 24941808
TI  - [Mellitin induced acute kidney injury and continuous renal replacement therapy in
      goat model].
AB  - OBJECTIVE: To establish a goat model of melittin induced acute kidney injury
      (AKI), and to evaluate the therapeutic effect of continuous veno-venus
      heamofiltration (CVVH) in melittin- induced AKI. METHODS: Twelve male goats were
      randomized into three groups: control group, melittin induced AKI group (melittin
      group), and CVVH intervention group (CVVH group). The AKI goat model was
      established by the injection of melittin via the auricular vein for four times in
      48 h to reach a total dose of 0.5 mg/kg, then serum creatinine (Cr) and creatine
      kinase (CK) were tested every 6 h and urine output was record each hour. AKI was
      diagnosed when Cr level increased to the double value of control group, or the
      urine output decreased to less than 0. 5 mL/(kg x h) in 6 h. After the diagnosis
      of AKI, the animals in CVVH group received CVVH treatment for 12 h. At the end,
      the goats in all groups were sacrificed by anesthesia and kidney tissue samples
      were collected. Light microscopy and telectron microscopy observation were
      performed. Apoptosis was detected by immunohistochemistry and TUNEL technique.
      RESULTS: AKI was successfully induced by melittin in the goats. The Cr level in
      control group was (43.95 +/- 1.59) micromol/L, while (100.75 +/- 7.87) micromol/L
      in AKI group and (102.10 +/- 5.06) micromol/L in CVVH group. Cr level was lowered
      significantly after CVVH treatment [(45.02 +/- 2.41) micromol/L in control group
      vs. (108.60 +/- 9.40) micromol/L in AKI group vs. (64.13 +/- 5.82) micromol/L in
      CVVH group, P < 0.001]. Swelling and reduction of mitochondrial crests in AKI
      group were more obvious than those in CVVH group. Expression of caspase-3 and
      apoptosis cells percentage of renal tubules in AKI group were significantly
      higher than those in CVVH group. CONCLUSION: Melittin induced AKI model could be
      established in goats. CVVH could alleviate melittin induced AKI, probably in the
      mechanism to reduce the apoptosis of renal tubular cells.

PMID- 24941809
TI  - [Effect of KH902 in inhibiting suture induced corneal neovascularization].
AB  - OBJECTIVE: To evaluate the effect of topical KH902 on experimental corneal
      neovascularization (CNV) in rats. METHODS: Suture models of CNV were established
      in 60 adult healthy rats. The rats were randomly divided into 3 groups: Group A
      (20 rats) were treated with KH902 (KH902 30 mg/mL was injected subconjunctivally
      once every other day); Group B (20 rats) were treated with dexamethasone (0.1%
      dexamethasone was injected subconjunctivally once every other day); Group C (20
      rats) served as blank control. CNV growth were observed by slitlamp microscopy 3,
      7 and 14 d after suture. Medicines were administered 14 d after operations. CNV
      changes were observed and recorded 1, 7, 14, and 21 d after administration of
      medicines. VEGF expression in cornea was measured by immunohistochemistry.
      RESULTS: No significant differences were found in average areas of CNV between
      groups at 1 and 7 d after administration of medicines. At 14 and 21 d after
      administration of medicines, significant differences in average areas of CNV were
      found between Group A and Group C, and between Group B and Group C (P < 0.01).
      Maximum expression of VEGF in corneal stroma was observed 14 d after corneal
      suture. The expression of VEGF decreased with medications, which was associated
      with neovascularization. CONCLUSION: Topical use of KH902 inhibits corneal suture
      induced CNV in rats without significant adverse corneal effect on eyes.

PMID- 24941810
TI  - [Diagnostic value of ultrasound imaging in chronic gouty arthritis].
AB  - OBJECTIVE: To determine the diagnostic value of ultrasound imaging in chronic
      gouty arthritis. METHODS: Ultrasound imaging of 32 patients with chronic gouty
      arthritis were compared with those of 36 patients with non-gouty joint diseases.
      A logistic model was obtained to establish the associations between ultrasound
      appereances and gouty arthritis. Receiver operator characteristic (ROC) curve was
      constructed to evaluate the performance of the logistic model. RESULTS: A double
      contour sign of articular cartilage, a snowstorm appearance of the joint fluid,
      and a hyperecho around the periarticular tendon had diagnostic value for chronic
      gouty arthritis. According to the logistic regression analysis, the accuracy of
      predicting chronic gouty arthritis was 95.59% (65/ 68), and the area under curve
      of ROC was 3.987 +/- 0.011 (P < 0.05). CONCLUSION: A double contour sign of
      articular cartilage, a snowstorm appearance of the joint fluid, and a hyperecho
      around the periarticular tendon have diagnostic value. The combination of these
      appearances can improve diagnosis of chronic gouty arthritis.

PMID- 24941811
TI  - [Changes of plasma glucagon level in individuals with different glucose
      metabolism].
AB  - OBJECTIVE: To determine the levels of plasma glucagon and associated factors in
      individuals with different glucose metabolism. METHODS: One hundred and ten
      outpatient patients received an oral glucose tolerance test (OGTT) voluntarily.
      The patients were divided into three groups according to their OGTT results:
      normal glucose golerance (NGT) group (n=33), impaired glucose regulation (IGR)
      group (n=35), newly diagnosed type 2 diabetes (DM2) group (n=42). Plasma glucagon
      (GLC) and insulin (INS) at 0 min (0 h), 30 min (0.5 h), 60 min (1 h) and 120 min
      (2 h) were measured by radio immunity and electrochemiluminescence assay,
      respectively. We calculated the area of glucagon under the curve (AUCglc), the
      value of early phase glucagon secretion (deltaGLC = GLC(0.5 h) - GLC(0 h)) and
      the ratio of insulin to glucagon (INS/GLC). RESULTS: (1) There was no significant
      difference in the level of GLC(0 h) among the three groups (P > 0.05). (2)
      Patients in the IGR group had higher levels of GLC(0.5 h) and GLC(1 h), greater
      values of AUC(glc), and deltaGLC, and lower values of INS(0.5 h)/GLC(0.5 h) than
      those in the NGT group (P < 0.05). (3) Patients in the DM2 group had higher
      levels of GLC(0.5 h) and GLC(1 h), greater values of AUC(glc) and deltaGLC, and
      lower values of INS(0.5 h)/GLC(0.5 h) and INS(1 h)/GLC(1 h) than those in the NGT
      group (P < 0.05). (4) Patients in the DM2 group had higher levels of GLC(1 h),
      greater values of AUC(glc), and lower values of INS(0.5 h)/GLC(0.5 h), INS(1
      h)/GLC(1 h), and INS(2 h)/GLC(2 h), than those in the IGR group (P < 0.05). (5)
      The multiple linear regression analysis showed that the value of AUC(glc). was
      positively correlated with HOMA-IR (adjust R2 = 0.219, P = 0.001). CONCLUSION:
      There are no significant differences in fasting plasma glucagon levels among the
      individuals with different glucose metabolism. Hypersecretion of glucagon and
      reduced glucagon suppressing effect of insulin occur in IGR patients, which is
      exacerbated when DM2 are developed. HOMA-IR is an important factor associated
      with glucagon hypersecretion.

PMID- 24941812
TI  - [Effects of inhaled LPS on inflammation and mucus hypersecretion in the airway of
      asthmatic mice].
AB  - OBJECTIVE: To investigate the effects of LPS on inflammation and mucus
      hypersecretion in the airway of asthmatic mice. METHODS: Thirty clean BALB/c mice
      were randomly divided into three groups: asthmatic model group (AST group, n=10),
      LPS+ asthmatic group (LAS group, n=10), control group (NS group, n=10). Mice in
      the asthmatic model group were sensitized and challenged with ovalbumin (OVA).
      Mice in the LPS group were not only sensitized and challenged with OVA but also
      inhaled LPS. Mice in the control group were sensitized and challenged with normal
      sodium. Total cells and differential inflammatory cells in bronchoalveolar lavage
      fluid (BALF) were counted. The levels of IL-4 and TNF-alpha in BALF were
      determined by ELISA. Pathomorphological changes in the lungs were observed by
      hematoxylin-eosin (HE) staining. Goblet cells of the airway walls were observed
      by AB-PAS staining. The expression of Mucin-5ac (Muc5ac) in airway were
      determined by immunohistochemical staining. The expressions of Muc5ac mRNA in
      lung tissues were determined by real time fluorescence quantitative reverse
      transcription polymerase (real time-PCR). RESULTS: Mice in the LAS and AST groups
      had more total cells and eosinophil, monocytes and lymphocyte cells in BALF,
      higher levels of IL-4 and TNF-alpha in BALF, greater hyperplasia of goblet cells
      in the airway walls, and higher levels of expression of Muc5ac in lung tissues
      than those in the control group (P < 0.05). Mice in the LAS group had higher
      levels of airway inflammation and airway mucus hypersecretion in lung tissues
      than those in the AST group (P < 0.05). CONCLUSION: OVA stimulates lymphocyte and
      eosinophil cells in the airway inflammation of asthmatic mice. Goblet cell
      metaplasia and airway mucus hypersecretion are obvious in asthmatic mice. Higher
      levels of airway inflammation and mucus hypersecretion in lung tissues can be
      found in mice inhaled LAS compared with those in the AST group. LAS may stimulate
      inflammatory mediators.

PMID- 24941813
TI  - [Detection of 16S rRNA methylase genes and genotypes in ESBLs-producing
      enterobacteriaceae isolates from urinary tract infections].
AB  - OBJECTIVE: To study the prevalence of 16S rRNA methylase genes in extended
      spectrum-lactamascs (ESBLs)-producing Enterobacteriacea, and the correlations of
      16S rRNA methylase genes with anminoglycoside resistnace. METHODS: Seventy-four
      ESBLs-producing Enterobacteriacea stains were isolated from urinary tract
      infections. Minimal inhibitory concentrations (MICs) of 5 aminoglycosides against
      the ESBLs-producing Enterobacteriacea were detected by two-fold agar dilution
      method. PCR amplification and DNA sequencing were used for screening and
      identifying 16S rRNA methylase genes. The clonality of 16S rRNA methylase gene
      positive ESBLs-producing Enterobacteriaceae was assessed by multilocus sequence
      typing (MLST). RESULTS: The bacterial resistant rates to gentamycin, netilmicin,
      tobramycin,amikacin and isepamicin were 93.4%, 18.4%, 13.2%, 5.3% and 5.3%,
      respectively. Tweenty-two out of 74 clinical isolates were 16S rRNA methylase
      genes positive (29.7%), including 18 armA gene and 7 rmtB gene, and 3 strains
      with both genes. The resistant rates of those 22 strains to gentamycin ,
      netilmicin, tobramycin, amikacin and isepamicin were 100%, 100%, 59.1%, 18.2% and
      18.2%, respectively. Among 19 E. coli isolates, seven sequence types (STs) were
      identified, named as ST117 (12 strains), ST2003 (2 strains), ST3843 (1 strain),
      ST915 (1 strain), ST844 (1 strain), ST2581 (1 strain) and ST2922 (1 strain). MLST
      showed that 3 K. pneumoniae isolates were nonclonal. CONCLUSION: 16S rRNA
      methylase genes were widely distributed in urinary ESBLs-producing
      Enterobacteriacea, showing obvious relationship with the resistance to
      aminoglycosides. The therapy of Amikacin or Isepamicin may be considered in UTIs
      with 16S rRNA gene positive ESBLs-producing Enterobacteriacea.

PMID- 24941814
TI  - [Higher procalcitonin level in diabetic nephropathy patients compared with
      healthy volunteers].
AB  - OBJECTIVE: To investigate the difference of procalcitonin (PCT) level between
      uninfected diabetic nephropathy patients and healthy volunteers. METHODS: This
      study enrolled 76 patients with diabetes only [DM group, 24 h urinary micro
      albumin (mALB) < 30 mg/24 h], 81 patients with early DN (EDN group, mALB 30-300
      mg/24 h), 87 DN patients (DN group, mALB > or = 300 mg/24 h), and 82 age- and sex
      matched healthy volunteers. All the patients were free of systemic infection. PCT
      levels and various laboratory parameters including metabolic and kidney functions
      as well as inflammatory element profiles were assessed. RESULTS: The PCT level of
      DN group was significantly higher than that of healthy control group, DM group
      and EDN group (P < 0.001 or P < 0.05). Spearman's test showed a significant
      positive correlation between PCT and serum lactate dehydrogenase (LDH, r = 0.541,
      P < 0.01), Urine acid (UA) (r = 0. 320, P < 0.01), Urea (r = 0.324, P < 0.01),
      creatinine (Cr) (r= 0.403, P < 0.01), alpha-hydroxybutyrate dehydrogenase (alpha
      HBD) (r = 0.791, P < 0.01) and C-reactive protein (CRP) (r = 0.694, P < 0.001) in
      diabetic nephropathy patients respectively. CONCLUSION: Serum PCT level of
      patients with diabetic nephropathy is higher than that of healthy volunteers,
      which may be associated with minimal inflammation and kidney function damage.

PMID- 24941816
TI  - [Determination of dosage and effectiveness of propofol and ketamine for TIVA in
      adults].
AB  - OBJECTIVE: To evaluate the effectiveness of combined use of propofol and ketamine
      for total intravenous anesthesia (TIVA) in adults and to determine their optimal
      doses. METHODS: 100 adults with general anesthesia were randomly divided into
      five groups [K0, K0.5, K1, K1.5 and K2, with 0, 0.5, 1, 1.5 and 2 mg/ (kg x h)
      ketamine, respectively]. The dose of propofol administered during surgery and
      hemodynamics, respiratory recovery time, awakening time, steward score of
      recovery and adverse reactions of the patients were recorded. Ten patients from
      each group were randomly chosen to have plasma concentrations of propofol and
      ketamine examined. RESULTS: The dose of propofol and total price of the two drugs
      decreased with the increase of dosage of ketamine (P < 0.05). Better outcomes in
      recovery indexes and adverse reactions were observed in Group K1 compared with
      those in Group K1.5 and K2 (P < 0.05). Plasma concentrations of ketamine in Group
      K1, K1. 5 and K2 were higher than those in Group K0.5 (P < 0.05). Regression
      analyses showed a positive correlation between 'dose of ketamine and operation
      time' and 'respiratory recovery time and awakening time' and a negative
      correlation between 'dose of ketamine and operation time' and 'steward score of
      recovery'. 'Dose of ketamine' was also associated with dreams, asleep after
      awakening, nystagmus and visual changes. The dose ratio of ketamine and propofol
      was associated with dizzy and adverse reactions. CONCLUSION: Continuous pump
      infusion of 1 mg/(kg x h) ketamine for TIVA in adults can reduce dosage of
      propofol and minimize adverse effects of ketamine.

PMID- 24941815
TI  - [Levels of serum lipids in rural populations with diabetes and pre-diabetes in
      Chengdu].
AB  - OBJECTIVE: To investigate the serum lipid levels in rural residents with diabetes
      and pre-diabetes conditions in Chengdu. METHODS: Random cluster sampling method
      was employed to select participants of 35-70 year-old rural residents in Chengdu.
      The participants (n=971) were given standard 75 g oral glucose tolerance tests
      (OGTT) and divided into five groups: impaired fasting glucose (IFG) group,
      impaired glucose tolerance (IGT) group, IFG and IGT (IFG+ IGT) group, diabetes
      mellitus (DM) group and normal glucose tolerance (NGT) group. Their serum total
      cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c)
      and low density lipoprotein cholesterol (LDL-c) were measured. RESULTS: The age
      adjusted standardized prevalence of DM and pre-diabetes in rural residents in
      Chengdu were 12.8% and 34.5%, respectively, without significant gender
      differences. IGT was the most common type of abnormal glucose metabolism in pre
      diabetes. High serum TG and LDL-c and low serum HDL-c were found in 45.9%, 30.6%
      and 9.9% participants with DM, respectively. High serum LDL-c and TG and low
      serum HDL-c were found in 38.1%, 30.6% and 7.6% of participants with IGR.
      Participants with DM or/and IGR had higher levels of LDL-c and TG and lower
      levels of HDL-c than those in the NGT group. CONCLUSION: Pre-diabetes and
      diabetes are prevalent in rural residents in Chengdu, which are usually
      accompanied with various degrees of dyslipidemia.

PMID- 24941817
TI  - [Visual performance of amblyopia before and after correcting higher order
      aberrations with adaptive optics system].
AB  - OBJECTIVE: To investigate visual performance of monocular amblyopia before and
      after correcting higher order aberrations (HOAs) with adaptive optics system.
      METHODS: Visual acuity (VA) and contrast sensitivity (CS) thresholds of ten
      monocular amblyopes were measured before and after correcting higher order
      aberrations with adaptive optics system. The change of them were analyzed.
      RESULTS: A significant improvement of 0.16 times on average (P = 0.005) visual
      acuity of the amblyopic eyes and 0.34 times on average (P < 0.001) CS thresholds,
      mainly improved at 24 cpd were observed. CONCLUSION: The visual performance of
      amblyopic eyes can be improved after correcting higher order aberrations, and
      HOAs affect CS at some high spatial frequency.

PMID- 24941818
TI  - [Relationship between depression and thyroid hormone levels in patients with
      Graves disease].
AB  - OBJECTIVE: To explore the relationship between depression and thyroid hormone
      levels in Graves disease patients. METHODS: A total of 188 out-patients with
      Graves disease were enrolled in this study. All patients received the
      measurements of Zung Self-Rating Depression Scale (SDS) and serum thyroid
      stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and
      TSH receptor antibodies (TRAb). RESULTS: All the patients were divided into 3
      groups: high FT4 level group (n=65), normal FT4 level group (n=113) and low FT4
      level group (n=19). There were statistically significant difference of SDS scores
      (P < 0.05) in 3 groups, but no significant difference in the occurrence of
      depression (P > 0. 05). In Pearson correlation analysis, SDS score was positively
      correlated with serum FT3 (r = 0.372, P < 0.001) and FT4 level (r = 0.288, P <
      0.001), negatively correlated to serum TSH level but no statistically significant
      (r = -0.028, P = 0.614). logistic regression analysis showed that TSH (P =
      0.131), FT4 (P = 0.637), and FT3 (P = 0.208) were not the independent risk
      factors for the occurrence of depression. CONCLUSION: Although the prevalence of
      depression is high in Graves disease patients, there is no close correlation
      between depression and the level of thyroid hormone.

PMID- 24941819
TI  - [Down-regulation effect of TGF-beta1 on expression of VEGF in bladder cancer cell
      line].
AB  - OBJECTIVE: To explore the down-regulation effect of transforming growth factor
      beta1 (TGF-beta1) on the expression of vascular endothelial growth factor (VEGF)
      in bladder cancer cell line EJ cell strain. METHODS: The siRNA expression vectors
      of TGF-beta1, gene were constructed, the highest inhibition target sequence was
      screened and selected by real time-PCR and ELISA, and then the vectors were
      transfected into EJ cells, the expression level of VEGF mRNA was detected by Real
      time-PCR. RESULTS: TGF-beta1 targeting expression vectors were successfully
      constructed, Real time-PCR and ELISA screened the highest inhibition target
      sequence (the lowest expression level of TGF-beta1 mRNA was 0.92 +/- 0.19; ELISA
      result was 50.08 +/- 5.85). The relative expression level of VEGF mRNA in TGF
      beta1 siRNA group was the lowest, indicating that the expression of VEGF was
      decreased by silencing TGF-beta1, gene. CONCLUSION: Inhibition of TGF-beta1 gene
      expression could down regulate the expression of VEGF in bladder neoplasm.

PMID- 24941820
TI  - [Association of chronic obstructive pulmonary disease and lung cancer].
AB  - OBJECTIVE: To investigate the association between chronic obstructive pulmonary
      disease (COPD) and lung cancer. METHODS: A case-control study was undertaken,
      with 180 cases of lung cancer and 200 cases of controls. RESULTS: The odd of lung
      cancer was higher in patients with COPD, emphysema, chronic bronchitis, and
      pulmonary tuberculosis (P < 0.05). The odd of lung cancer increased significantly
      in patients with a family history of lung cancer or COPD (P < 0.05). The odd of
      lung cancer also increased when forced expiratory volume in one second (FEV1) <
      80%. CONCLUSION: Patients with COPD or a family history of COPD have higher risk
      of lung cancer.

PMID- 24941821
TI  - [Impact factors of distress in patients with lung cancer-associated pain].
AB  - OBJECTIVE: To study the impact factors of psychological distress in patients with
      lung cancer-associated pain. METHODS: The cross-sectional study was applied to
      lung cancer pain patients received treatments in Cancer Center of West China
      Hospital of Sichuan University in Chengdu from July 2011 to December 2011 by
      distributed questionnaires. The general information of the patients, Brief Pain
      Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) were
      included in the questionnaire to evaluate the states of distress, pain and the
      factors related to the total distress score. RESULTS: Totally 172 effective
      questionnaires were obtained in 200 delivered questionnaires. The average pain
      score of the patients was 3.67 +/- 1.27. The Spearman correlation analysis showed
      that depression score, anxiety score, distress score were positively correlated
      with the pain intensity (P < 0.05). Patients with positive anxiety symptom was
      29.0%, the depression was 29.0%, and distress was 68.6%. Mutiple linear
      regression analysis showed that gender (p = 0.152, P = 0.024), age (beta = 
      0.150, P = 0.023), marital status (beta = -0.239, P = 0.000) could affect the
      total score of distress; gender (beta = 0.154, P = 0.013), age (beta = -0.165, P
      = 0.007), the clinical pathological stage (beta = 0.155, P = 0.011) could affect
      the anxiety score; marital status (beta = -0.133, P = 0.047) could affect the
      depression score. CONCLUSION: The genders, age, marital status of the patients
      are related to the psychological distress of lung-cancer-pain patients.

PMID- 24941822
TI  - [Advances in the clinical research of gastro-esophageal reflux disease and
      functional gastrointestinal diseases].
AB  - Gastro-esophageal reflux disease (GERD) and functional gastrointestinal diseases
      (FGIDs) are common digestive diseases with an increasing concern. Both of them
      share similar pathogenesis, symptoms overlapping and merged mental psychological
      factors, which cause lack of standardization in diagnosis and poor response to
      treatment. The topics of this issue focused on the characteristics of motility
      dysfunction in different subtype of GERD and treatment priorities, main points of
      diagnosis and treatment of atypical-GERD with extra-esophageal symptoms as the
      primary presenting manifestation, status and characteristics of symptom
      overlapping between GERD and FGIDs, as well as the influence of symptom
      overlapping and mental psychological factors to life quality of GERD and FGIDs
      patients. With these advances in clinical research translating into clinical
      practice, it becomes promising to improve the standardization of diagnosis and to
      optimize the treatment of these diseases, which could lead to the change of
      therapeutic goal from simply alleviation of symptoms into the improvement of life
      quality with more concern of symptoms indicators.

PMID- 24941823
TI  - [Association between acid reflux and esophageal dysmotility in patients with
      gastroesophageal reflux disease].
AB  - OBJECTIVE: To investigate the association between esophageal motility and acid
      reflux in patients with gastroesophageal reflux disease (GERD). METHODS: A total
      of 94 patients with typical reflux symptoms such as heartburn, regurgitation and
      chest pain, whose score (Sc) of reflux diagnostic questionnaire (RDQ) was greater
      than or equal to 12 were enrolled in the study. Each participant was evaluated by
      upper gastrointestinal endoscopy, high resolution manometry (HRM) of esophagus
      and 24 h esophageal pH monitoring. The participants were divided into groups of
      reflux esophagitis (RE) and non-erosive reflux disease (NERD) on the basis of
      endoscopy findings. The 24 h esophageal pH monitoring categorized participants
      into physiologic reflux (pH) and pathologic reflux (pH+). The characteristics of
      esophageal motility and acid reflux were compared between the two groups of
      participants. RESULTS: Lower but non-significant differences (P > 0.05) were
      found in pressure of lower esophageal sphincter (LESP), length of lower
      esophageal sphincter (LESL), esophageal contraction amplitude (CA), distal
      contractile integral (DCI) and effective peristalsis proportion (EPP) in the
      participants in the RE group compared with those in the NERD group. Participants
      in the RE group had significantly higher prevalence of reduced LESP (63.0% vs.
      31.7%, P < 0.01) and hiatus hernia (HH) (37.0% vs. 14.3%, P < 0.05) than those in
      the NERD group, pH+ was more prevalent in the RE group than in the NERD group
      (63.0% vs. 17.5%, P < 0.01). Indicators of 24 h esophageal pH monitoring were
      significantly higher in participants in the RE group compared with those in the
      NERD group (P < 0.05). Participants with pH+ had significantly lower LESP, CA and
      higher HH and prevalence of reduced LESP compared with those with pH (P < 0.05).
      LESL, DCI and EPP were lower in those with pH+ compared with those with pH-, but
      without statistical significance (P > 0.05). CONCLUSION: RE is closely associated
      with acid reflux and hiatus hernia. Esophageal dysmotility is more likely to
      appear in patients with pH+. The interaction of acid reflux and esophageal
      dysmotility may play a role in GERD.

PMID- 24941824
TI  - [Comparison of clinical features between gastroesophageal reflux diseases with
      atypical and typical symptoms].
AB  - OBJECTIVE: To study the differences between gastroesophageal reflux disease
      (GERD) with atypical symptoms (a-GERD) and typical symptoms (t-GERD). METHODS: 30
      patients of suspected a-GERD were recruited and examined with upper
      gastrointestinal endoscopy, high-resolution manometry (HRM), 24 h esophageal
      multichannel intra-luminal impedance monitoring with pH sensor (MII-pH) and
      proton pump inhibitor (PPI) trials. The results were compared with those of 33
      cases of GERD with typical symptoms. RESULTS: Among the 30 patients of suspected
      GERD, 24 were confirmed with a-GERD. One third of those patients were over sixty
      years old, significantly higher than those with typical GERD (P < 0.05). No
      significant differences in prevalence of esophageal mucosa breakage and
      esophageal manometry readings were found between the two groups (P > 0.05). The a
      GERD patients had higher data readings in 24 h esophageal MCII-pH monitoring than
      the t-GERD patients (P < 0.05). Supine type of GER and mixed reflux were
      predominately seen in the a-GERD patients, while upright type of GER was
      predominate seen in the t-GERD patients. The response rate of PPI in the a-GERD
      patients was significantly lower than that in the t-GERD patients when a course
      of standard dosage of PPI was given (45.8% vs. 78.8%, P < 0.01). But there was no
      significant difference in PPI response between these two groups when a second
      course with double standard dosage of PPI combined with pro-motility agents were
      given (72.7% vs. 88.0%, P < 0.05). CONCLUSION: Compared with patients of t-GERD,
      older onset age, more severe degree of acid reflux are presented in patients of a
      GERD. a-GERD should be considered when it is hard to explain the symptoms of
      upper part of the chest in clinical practice. 24 h esophageal MII-pH monitoring
      and/or diagnostic therapy with double standard dosage of PPI helps make a correct
      diagnosis.

PMID- 24941825
TI  - [Symptom overlaps between functional heartburn, functional dyspepsia, and
      irritable bowel syndrome].
AB  - OBJECTIVE: To determine symptom overlaps between functional heartburn (FH),
      functional dyspepsia (FD), and irritable bowel syndrome (IBS). METHODS: One
      hundred and ten patients with frequent heartburn but no mucosa breakage under
      endoscopy were enrolled consecutively. They were required to fill out a
      questionnaire. The overlapped symptoms of FD and IBS symptoms were screened using
      Rome ill criteria. The participants were also examined using Hamilton anxiety
      scale/Hamilton depression scale. All of the participants were followed with 24 h
      esophageal multichannel intra-luminal impedance monitoring with pH sensor (MII
      pH) monitoring and proton pump inhibitor (PPI) trials. The participants were
      divided into non-erosive reflux disease (NERD) and FH groups. The prevalence of
      symptom overlaps FD and IBS, between NERD and FH groups was analyzed. RESULTS:
      Women were more likely to present with FH than with NERD (P < 0.05). The
      participants with FH had higher prevalence of anxiety and depression than those
      with NERD (92% vs. 75%, 88% vs. 65% respectively, P < 0.05). Fifty-two (47.3%)
      patients with heartburn symptom had FD symptoms; 31 (28.2%) had IBS symptoms, and
      10 (9.09%) had both FD and IBS symptoms. Patients with FH were more likely to
      have symptom overlaps of FD and IBS than those with NERD (62% vs. 35%, 48% vs.
      11.7%, respectively; P < 0.01). Epigastric pain syndrome (EPS), a subtype of FD,
      was slightly more likely to have overlapped NERD and FH symptoms than
      postprandial discomfort symdrome (PDS). But the difference was not significant
      (29. 1% vs. 18.2%, P > 0.05). IBS-diarrhea was also slightly more likely to have
      overlapped NERD and FH symptoms than IBS-constipation. Again, the difference was
      not significant (16.4% vs. 11.8%, P > 0.05). CONCLUSION: Female, higher
      prevalence of anxiety and depression, overlapped FD and IBS symptoms are more
      likely to appear in FH patients than in NERD patients.

PMID- 24941826
TI  - [Clinical features, quality of life and psychological health of patients with
      irritable bowel syndrome and functional dyspepsia].
AB  - OBJECTIVE: To investigate severity of gastrointestinal symptoms, quality of life,
      and mental health status of patients with irritable bowel syndrome (IBS) and
      functional dyspepsia (FD). METHODS: IBS patients were enrolled consecutively at
      the Outpatient Department of Gastroenterology, West China Hospital, Sichuan
      University from September 2012 to May 2013. The participants were divided into
      two groups according to their appearance with FD. Ten healthy volunteers served
      as normal controls. A questionnaire survey was undertaken to measure scores of
      gastrointestinal symptom rating scale (GSRS), Chinese IBS-quality of life (ChIBS
      QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and medical
      conditions. RESULTS: Twenty-five (41.7%) IBS patients were overlapped with FD
      (IBS-FD). The IBS-FD patients had significantly higher scores of GSRS than IBS
      patients and healthy volunteers (P < 0.05). The IBS-FD patients saw doctors more
      frequently than IBS patients (P < 0.05). Neither anxiety nor depression were
      observed in healthy volunteers. The IBS patients were more likely to present mild
      anxiety and depression, while the IBS-FD patients were more likely to present
      moderate to severe anxiety and depression. The IBS-FD patients had significantly
      higher prevalence of anxiety and depression than IBS patients (80.0% vs. 51.4%,
      76.0% vs. 48.6% respectively, P < 0.05). Scores of GSRS, ChIBS-QOL and prevalence
      of anxiety and depression were the highest in the IBS-FD patients with
      constipation (IBS-C-FD, P < 0.05). CONCLUSION: IBS-FD patients especially those
      with constipation suffer more gastrointestinal discomforts, and are more likely
      to suffer from anxiety and depression and poor quality of life compared with
      those with IBS only.

PMID- 24941827
TI  - [Determination of dimemorfan in human plasma and urine with HPLC-MS/MS].
AB  - OBJECTIVE: To develop a sensitive and reproducible HPLC-MS/MS method for
      analyzing dimemorfan in human plasma and urine. METHODS: Dimemorfan was extracted
      from plasma and urine by redistilled ether, with lidocaine serving as the
      internal standard (IS). The analysis was performed on a column of ultimate C18
      (50 mm x 4.6 mm, 5 microm) with the mobile phase consisting of methyl alcohol
      water-formic acid = 75:25 : 0.05 at a flow rate of 0. 2 mL/min. Dimemorfan was
      detected by API 3000 mass spectrometer, with multiple reaction monitoring after
      protonated with ESI in positive electron ionization mode. The ion pairs being
      detected were (m/z) 256.4-->155. 3 (dimemorfan) and 235.4-->86.1 (lidocaine),
      respectively. RESULTS: The regression equation for dimemorfan showed excellent
      linearity (r = 0.995 7) from 0. 025 to 5.0 ng/mL of plasma with detecting
      limitation of 0.025 ng/mL and perfect linearity (r = 0.9983) from 0.1 to 20.0
      ng/mL of urine with detecting limitation of 0.1 ng/mL. The method recoveries of
      dimemorfan in plasma and urine were ranging from 103.38% to 106.88% and 90.05% to
      101.40%, respectively. The maximum intra-day and inter-day relative standard
      deviations (RSD) of concentration of dimemorfan were 5.92% and 5. 70% (for
      plasma), 10.35% and 8.80% (for urine), respectively. CONCLUSION: This new method
      was validated to be accurate and sensitive to determinate the concentration of
      dimemorfan in plasma and urine samples, and can be applied for pharmacokinetic
      studies of dimemorfan.

PMID- 24941828
TI  - [Characteristics of hydroxyapatite/PMMA nanocomposites for provisional
      restoration and its biocompatibility with human gingival fibroblasts].
AB  - OBJECTIVE: To formulate hydroxyapatite (HA)/polymethyl methacrylate (PMMA)
      composites with improved cytocompatibility for provisional restoration. METHODS:
      Nanocomposites with 20 wt%, 30 wt%, 40 wt%, and 50 wt% HA/PMMA (H/P) were
      developed and examined using X-ray photoelectron spectroscopy (XPS) and scanning
      electron microscope (SEM). Human gingival fibroblasts were cultured on those
      HA/PMMA discs and investigated by fluorescent staining on 24 h and MTT assay at 1
      d, 3 d, 5 d and 7 d. RESULTS: Chemical integration of HA/PMMA interface was
      confirmed by XPS. Typical fusiform cells with adhesion spots were detected on 40
      wt% and 50 wt% H/P discs. MTT results showed insignificant differences in cell
      growth between 40 wt% H/P and pure titanium (Ti, P > 0.05), while the other H/P
      discs showed significantly lower cell growth than pure Ti (P < 0.05). CONCLUSION:
      40 wt% H/P might be a promising candidate for provisional dental implant
      restoration and for esthetic gingival contour.

PMID- 24941829
TI  - [Optimal cut-off value of phalangeal radiographic absorptiometry to identify
      osteoporosis in postmenopausal women].
AB  - OBJECTIVE: To study the optimal cut-off value of phalangeal radiographic
      absorptiometry (RA) to identify osteoporosis in postmenopausal women. METHODS: A
      total of 650 postmenopausal women were recruited in this study. Bone mineral
      density (BMD) at lumbar spine and left proximal femur neck was measured by dual
      energy X-ray absorptiometry (DXA) as the standard method to identify
      postmenopausal osteoprosis. Phalangeal bone density was estimated by the use of
      RA. Optimal cut-off value of phalangeal RA was determined using a ROC curve for
      screening the ostreoporosis cases. RESULTS: When the cut-off value of phalangeal
      RA was T score < or = -2.5, the sensitivity was 74.2%, the specificity was 72.9%.
      When the cut-off value was T score < or = -2.21, the sensitivity was 81.4%, the
      specificity was 62.0%. CONCLUSION: The cut-off value of phalangeal RA as T score 
      2.21. which has higher sensitivity could be optimal to identify postmenopausal
      osteoporosis.

PMID- 24941830
TI  - [Clinical characteristics and prognosis of patients with cerebral venous sinus
      thrombosis in southwest China].
AB  - OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a rare cerebral vascular
      disease. Early diagnosis and treatments are crucial for a better prognosis. This
      study investigated the clinical characteristics and risk factors associated with
      the prognosis of patients with CyST. METHODS: From Jan 2009 to Jan 2013, patients
      who were admitted to the Department of Neurology of West China Hospital with
      confirmed CVST (according to the 2006 guideline of European neurology with
      neuroimaging when necessary) were consecutively recruited. Their medical records
      including demographic information and detailed clinical data were analyzed. The
      functional outcome of CVST was assessed 12 months after discharge using the
      modified Rankin Scale (mRS). RESULTS: A total of 73 patients were enrolled in
      this study. Acute and chronic onset of illness accounted for 13.7% and 35.6% of
      all patients, respectively. The earliest common symptom was headache (90.4%).
      Other initial symptoms included decreased visual acuity or blurred vision (2.7%),
      unilateral limb weakness (2.7%), diplopia (1. 4 9/o) and seizure (1.4%). CT scan
      was conducted in 46 patients (63.3%), which revealed 8 (17.4%) cases of cerebial
      hemorrhagic infarction. Delta sign and cord sign was shown in 34.8% and 30.4% CT
      imaging, respectively. The MRI scan confirmed that 27. 5% of those patients had
      encephaledema, 55% had delta sign and 45% had cord sign. The commonly involved
      location of CVST was right lateral sinus (68.5%), left lateral sinus (57.5%),
      ongitudinal sinus (53. 4%), left sigmoid sinus (50.7%), right sigmoid sinus
      (47.8%), confluence sinuum (32.9%), nferior sagittal sinus (21.900), sinus rectus
      (20.5%), jugular vein (12. 3%) and cerebral vein (9.6%). During the 12-month
      follow-up, 6.8% patients died, 72.6% had good mRS outcome (<2) and 27.4% had poor
      mRS outcome (> OR =2). The regression analysis identified epilepsy and papilledma
      as independent predictors of poor prognosis of CyST. CONCLUSION: It is difficult
      to recognize CVST at an early stage due to its diverse clinical presentations.
      Neuroimaging may be helpful for the diagnosis. Epilepsy and papilledema are
      potentially independent predictors for the 12-month functional outcome of
      patients with CVST.

PMID- 24941831
TI  - [Clinical outcome of 489 patients with diffuse large B-cell lymphoma and
      associated factors].
AB  - OBJECTIVE: To investigate the clinical outcome of 489 patients with diffuse large
      B-cell lymphoma (DLBCL), and to identify factors associated with the clinical
      outcome. METHODS: Medical records of 489 DLBCL patients admitted to the West
      China Hospital of Sichuan University from Jan 2000 to Dec 2010 were
      retrospectively reviewed. The patients were divided into CHOP and RCHOP
      (rituximab plus CHOP) groups depending on their chemotherapy regimens. The
      clinical outcomes of the two groups of patients were compared. RESULTS: The RCHOP
      group had a higher response rate than the CHOP group (84.3% vs. 75.6%, P =
      0.015). The multivariate analysis showed that splenomegaly, low absolute
      lymphocyte count (ALC), high IPI scores, and CHOP was associate with the low
      overall-response rate. In the CHOP group, low ALC (OR = 2.060, 95% CI: 1.159
      3.661, P = 0.014) and high IPI scores (OR= 2. 157, 95% CI: 1.170-3.978, P =
      0.014) were associate with low response rate. In the RCHOP group, anemia (OR =
      3.010, 95% CI: 1.238-7.314, P = 0.015) and high IPI scores (OR = 2.872, 95% CI:
      1.193-6. 914, P = 0.019) were associate with low response rate. For patients with
      0.8 x 10(9)/L-1.0 x 10(9)/L ALC, RCHOP therapy was more effective than CHOP. The
      expression of Bcl-2 and the phenotype of immuno-classification (GCB/non-GCB) were
      not associated with the difference of overall response rate between the CHOP and
      RCHOP groups. CONCLUSION: RCHOP therapy increases the overall response rate
      compared with CHOP alone. Low ALC and anemia is associate with low response rate
      to CHOP and RCHOP therapy, respectively.

PMID- 24941832
TI  - [Characteristics of newly diagnosed diabetes patients with young onset in the
      West China Hospital of Sichuan University].
AB  - OBJECTIVE: To investigate the clinical characteristics, metabolic status, insulin
      resistance and insulin secretory function of diabetic patients with early onset.
      METHODS: The study was undertaken in the West China Hospital of Sichuan
      University. Characteristics of 342 admitted diabetic patients with early onset
      (EOD group, diagnosed at age 15-45 years old) were reviewed and compared with 296
      admitted patients with late onset (LOD group, diagnosed at age >45 years old).
      All of the participants had negative islet autoantibodies. Homeostasis model
      assessment 2 of insulin resistant (HOMA2-IR) and HOMA2 of insulin sencitivity
      (HOMA2-% S) were measured to estimate insulin resistance and insulin sensitivity.
      HOMA2 of beta-cell function (HOMA2-% beta) index was used to estimate beta-cell
      secretory function. We also compared clinical characteristics and metabolic
      status between the two groups. RESULTS: EOD patients were more likely to have
      ketosis, ketoacidosis, insulin therapy and positive diabetic family history than
      LOD patients (P < 0.05). Levels of systolic blood pressure (SBP), diastolic blood
      pressure (DBP), body mass index (BMI), waist-to-hip ratio (WHR), fasting and
      postprandial insulin (Fins, PIns), fasting and postprandial plasma C-peptide
      (FCP, PCP) were significantly lower, and glycosylated hemoglobin A1c (HbA1),
      triglycerides (TG), fasting and postprandial blood glucose (FPG, PPG) were
      significantly higher in EOD patients than in LOD patients (P < 0.05). EOD
      patients had lower prevalence of hypertension, central obesity, hyperuricemia,
      metabolic syndrome (MS) and co-exist of three or more metabolic disorders than
      LOD patients (P < 0.05). EOD patients had decreased levels of HOMA2-% beta,
      deltaI30/deltaG30 and HOMA2-IR, increased HOMA2-%S, and increased proportions
      with FCP < 0.2 nmol/L and FIns < 2.9 microU/mL compared with LOD patient (P <
      0.05). Linear regression analyses showed that HOMA2-%beta, deltaI30/deltaG30,
      positive diabetic family history were independent risk factors predicting early
      onset of diabetes. CONCLUSION: Early onset diabetic patients are characterized
      with low prevalence of metabolic disorders, insulin resistance and severe insulin
      secretion dysfunction. Loss of beta-cell function may play a major role in the
      development of early onset diabetes in this population.

PMID- 24941834
TI  - [The effect of equilibrium psychological intervention in wounded patients in
      Lushan earthquake].
AB  - OBJECTIVE: To investigate the early psychological effect of the equilibrium
      psychological intervention on the person who were injured in the disaster
      incident. METHODS: The equilibrium psychological intervention was used to the
      injured person in the Lushan earthquake during the early period. The GHQ-12, HAMA
      and HAMD were used before and after the evaluation. RESULTS: The score of the GHQ
      12 decreased from (3.488 +/- 2.900) to (1.610 +/- 0.840), which showed the
      significant differences (P < 0.001). The total score of the HAMA and the score of
      the somatic anxiety factor and mental anxiety factor decreased significantly,
      compared with the base line (P < 0.001 respectively). The total score of the HAMD
      and the score of the sretardation factor, somatization factor and sleep disorder
      factor also decreased significantly, compared with that of the base line (P <
      0.005 respectively). CONCLUSION: The equilibrium psychological intervention has
      the positive effect on the persons who were injured in the disaster incident
      during the early period.

PMID- 24941833
TI  - [Safety and efficacy of subcutaneous administration of bortezomib in the
      treatment of multiple myeloma].
AB  - OBJECTIVE: To analyze the efficacy and safety of subcutaneous administration of
      bortezomib in the treatment of multiple myeloma (MM) patients. METHODS: A total
      of 26 MM patients were enrolled in this study and treated with BDT (bortezomib
      dexamethasone-thalidomide). In the 26 MM patients, 12 patients received
      subcutaneous administration of Bortezomib while 14 patients received conventional
      intravenous administration. The outcomes and adverse effects of two groups were
      retrospectively evaluated and compared. RESULTS: Overall response (OR) rates in
      the two groups were 75.00% and 71.43% respectively, in which complete remission
      (CR) plus very good complete remission (VGPR) rates were 50.00% and 47.14%, while
      CR rates were 16.67% and 28.57%. There were no statistically significant
      difference (P > 0.05). Time to achieve effectiveness in two groups was similar (P
      > 0.05). More than half patients in both groups achieved partial remission after
      the first treatment course and CR after the fourth course. Compared to the
      intravenous group, peripheral neuropathy rates remained significantly lower in
      subcutaneous group (16.67% vs. 64.29%, P = 0.021). The intravenous group had
      7.14% grade 3 or worse, peripheral neuropathy but none found in the subcutaneous
      group. Rash occurred only in subcutaneous group (66.67%), but it was local, mild
      and transitional. No significant differences of other adverse events between the
      two groups were observed. CONCLUSION: Subcutaneous administration of bortezomib
      offers similar efficacy to standard intravenous administration in the treatment
      of multiple myelom, with an improved safety for lower rate of peripheral
      neuropathy.

PMID- 24941835
TI  - [Treating chronic persistent bronchial asthma children with abnormal myocardial
      enzyme spectrum by Yupingfeng powder: an efficacy observation].
AB  - OBJECTIVE: To observe the clinical efficacy of treating chronic persistent
      bronchial asthma (CPBA) children with abnormal myocardial enzyme spectrum (AMES)
      by Yupingfeng Powder (YP) combined routine therapy. METHODS: From January 2010 to
      December 2012, 156 CPBA children patients with AMES were randomly assigned to the
      treatment group (80 cases) and the control group (76 cases). All patients
      received routine treatment (inhaled corticosteroids and/or leukotriene
      regulator). Besides, those in the treatment group took YP. The treatment duration
      was 3 months. The scores of children asthma control test (C-ACT), pulmonary
      function (FEV,% and PEF%), myocardial enzyme spectrum were observed before and
      after treatment, and 3 months before and after treatment. The myocardial enzyme
      spectrum of 40 healthy children at the baby clinics during the same period were
      recruited as the control. RESULTS: Compared with the control group, creatine
      kinase isoenzyme (CK-MB), creatine kinase(CK), and lactate dehydrogenase (LDH)
      increased in the two treatment groups (P <0.01), but there was no statistical
      difference in AST (P >0.05). Compared with before treatment in the same group, CK
      MB, CK, LDH, and AST decreased in the treatment group after treatment and 3
      months after treatment (P <0.01). CK-MB, CK, LDH, and AST decreased in the
      control group 3 months after treatment (P <0.01, P <0.05).Compared with after
      treatment, CK decreased in the control group 3 months after treatment (P <0.01).
      C-ACT score, FEV(1),%, and PEF% all increased in the two groups after treatment
      and 3 months after treatment (P <0.01, P <0.05). Compared with after treatment in
      the same group, CK decreased in the control group 3 months after treatment (P <0.
      01). Compared with the control group in the same period, post-treatment CK-MB and
      CK decreased (P <0. 01, P <0. 05), while post-treatment C-ACT score, FEV, %, and
      PEF% increased (P <0.05) in the treatment group (P <0.05). CONCLUSION: YP could
      strengthen specific and non-specific immunity of the organism, and improve
      clinical symptoms and the level of myocardial enzyme spectrum.

PMID- 24941836
TI  - [Effect of Zhifei mixture combined western drugs on symptoms and signs of
      children with mycoplasma pneumonia].
AB  - OBJECTIVE: To observe the effect of three Chinese medical formulae (Zhifei
      Mixture I , Zhfei Mixture II, and Zhifei Mixture II) on main and secondary
      symptoms and signs of children with Totally 70 mycoplasma pneumonia in treating
      three types of children mycoplasma pneumonia. METHODS: children with mycoplasma
      pneumonia were assigned to the control group (38 cases) and the treatment group
      (32 case). All patients were intravenously injected with Azithromycin and took
      Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution. Those in the
      treatment group additionally took Zhifei Mixture I , Zhfei Mixture II, and Zhifei
      Mixture Ill by syndrome typing. Their main and secondary symptoms and signs were
      observed before and after treatment (main symptoms and signs covered fever,
      cough, abundant sputum, short breath, and anoxia; secondary symptoms and signs
      covered aversion to cold, heart rate, facial complexion, spirit, appetite, and
      sweating). RESULTS: Seven patients were lost in this study. Compared with before
      treatment in the same group, scores for main and secondary symptoms and signs
      decreased in the treatment group (P <0.01). The therapeutic effect on fever and
      cough was obviously better in the control group (P <0.01). The main and secondary
      symptoms and signs were more obviously improved in the treatment group than in
      the control group (P <0.01). Commpared with the control group, scores for main
      and secondary symptoms and signs decreased more in the treatment group (P <0.01).
      Patients' main and secondary symptoms and signs were more obviously improved (P
      <0.05). CONCLUSIONS: Zhifei Mixture combined Western drugs could significantly
      improve main and secondary symptoms and signs of mycoplasma pneumonia children
      patients. Its efficacy was superior to that of using Western medicine alone.

PMID- 24941837
TI  - [Effect of integrated Chinese medical treatment (as maintenance therapy) on the
      survival time of patients with advanced non-small-cell lung cancer: a clinical
      study].
AB  - OBJECTIVE: To observe clinical effect of integrated Chinese medical (CM)
      treatment (as maintenance therapy) on the progression-free survival (PFS) and
      overall survival (OS) in patients with advanced non-small-cell lung cancer
      (NSCLC) after first-line chemotherapy. METHODS: The study was a prospective,
      randomized, controlled clinical trial. Totally 69 non-progressive advanced NSCLC
      patients treated with first-line chemotherapy were randomly assigned to the test
      group (34 cases) and the control group (35 cases). Patients in the control group
      were treated with one Western drug chemotherapy (Gemcitabine or Alimta or
      docetaxel). Those in the test group were treated with integrated CM treatment (CM
      decoction, CM Intravenous preparation, and point application). Each cycle
      consisted of 21 days. Treatment lasted till the disease progressed, or
      intolerable toxic/adverse reactions occurred, or patients refused to continue the
      treatment. Patients' life spans were regularly followed-up. RESULTS: (1) The
      median cycle of maintenance therapy was 2 cycles for two groups with no
      statistical difference (P =0.274). The median PFS was 12.43 weeks in the test
      group and 10.00 weeks in the control group, showing statistical difference (P
      =0.025). The middle survival time (MST) was 18.8 months in the test group and
      16.73 months in the control group, showing no statistical difference (P =0.437).
      CONCLUSION: CM treatment (as maintenance therapy) showed quail effect to one
      Western drug chemotherapy in prolonging patients' life span.

PMID- 24941838
TI  - [Effect of ligustrazine hydrochloride on coagulation reaction and inflammation
      reaction in single valve replacement patients with rheumatic heart disease
      undergoing cardiopulmonary bypass].
AB  - OBJECTIVE: To observe the protection effect of Ligustrazine Hydrochloride (LH) on
      coagulation reaction and inflammation reaction in single valve replacement
      patients with rheumatic heart disease undergoing cardiopulmonary bypass (CPB).
      METHODS: Totally 40 patients undergoing single valve replacement were recruited
      in the study and randomly assigned to the two groups, the treatment group and the
      control group, 20 in each group. In treatment group LH (3 mg/kg) was
      intravenously infused from the jugular vein. LH (3 mg/kg) was also added in the
      CPB priming. In the control group LH was replaced by equal amount of normal
      saline. Endothelial micro-particles (EMP) count was detected before CPB, 30 min
      after CPB, 1 h and 24 h after CPB finished. The coagulation reaction time (R),
      coagulation time (K), clotting formation velocity (alpha angle), maximum
      amplitude (MA), coagulation index (CI), platelet (PLT), hypersensitive C reactive
      protein (hs-CRP), IL-6, and IL-10 were detected before CPB, 1 h and 24 h after
      CPB finished. RESULTS: There was no statistical difference in aorta arresting
      time, period of CPB, post-operative drainage volume, plasma transfusion volume,
      post-operative respirator assistant time, and hospitalization time between the
      two groups (P >0.05). Compared with pre-CPB in the same group, the count of EMP
      was much higher at 30 min after CPB and 1 h after CPB finished (P < 0.01). R and
      K, hs-CRP, IL-6, and IL-10 increased at 1 h and 24 h after CPB finished (P
      <0.01,P < 0.05). The alpha angle,.MA, CI, and PLT decreased 1 h after CPB
      finished (P <0.01). The a angle increased, while CI and PLT decreased 24 h after
      CPB finished (P <0.05). Compared with the control group in the same period, the
      count of EMP was lower in the treatment group 30 min after CPB and 1 h after CPB
      finished (P <0. 05, P <0. 01). R and K values obviously decreased in treatment
      group 1 hour after CPB finished (P <0. 05), while a angle, MA, CI, and PLT
      increased (P <0. 05, P <0. 01). hs-CRP and IL-6 decreased in the treatment group
      1 h and 24 h after CPB finished (P <0.05), while IL-10 increased (P <0.05). The
      count of PLT increased 24 h after CPB finished in the treatment group (P <0. 05).
      CONCLUSION: LH had certain protection effect on the vascular endothelium
      undergoing CPB, and lower excessive activation of coagulation reaction and
      inflammation reaction in patients undergoing CPB.

PMID- 24941839
TI  - [Distribution laws of Chinese medical syndrome types and analyses of risk factors
      in senile hypertension patients: a clinical study].
AB  - OBJECTIVE: To explore the distribution laws of TCM syndrome types and to analyze
      the distribution of dynamic blood pressure curve, atherosclerosis, and age in
      senile hypertension patients. METHODS: Totally 1 131 senile hypertension patients
      were recruited from 7 provinces and municipal cities. Features of TCM syndromes,
      classification and distribution curves, and syndrome distribution laws were
      observed. The distribution curves of dynamic blood pressure, carotid
      atherosclerosis, and age were compared in each TCM syndrome types. RESULTS: There
      were four main syndrome types in 736 cases (56.15%), i.e., excessive accumulation
      of phlegm-dampness syndrome (210 cases, 16.02%), yin deficiency and hyperactivity
      of yang syndrome (177 cases, 13.50%), Gan-Shen yin deficiency syndrome (79 cases,
      6.03%), and deficiency of qi and yin syndrome (252 cases, 19.22%). Besides, there
      were two more sub-types, i.e., collateral obstruction by blood stasis syndrome
      and collateral obstruction by phlegm and stasis. Circadian blood pressure monitor
      was completed in 211 cases. Of them, abnormal circadian blood pressure occurred
      in 152 cases (accounting for 72. 38%); yin deficiency and hyperactivity of yang
      syndrome, excessive accumulation of phlegm-dampness syndrome, deficiency of qi
      and yin syndrome plus collateral obstruction by blood stasis syndrome were most
      often seen. Color ultrasound of carotid artery was performed in 660 patients of
      main syndromes. The incidence was quite higher in those of excessive accumulation
      of phlegm-dampness syndrome (182 cases, 27. 58%), deficiency of qi and yin
      syndrome plus collateral obstruction by blood stasis syndrome or collateral
      obstruction by phlegm and stasis (322 cases, 48.79%). Yin deficiency and
      hyperactivity of yang syndrome was dominant in patients 60 -79 years old, while
      deficiency of qi and yin syndrome and Gan-Shen yin deficiency syndrome were
      dominant in patients older than 80 years. CONCLUSIONS: Excessive accumulation of
      phlegm-dampness syndrome, yin deficiency and hyperactivity of yang syndrome, Gan
      Shen yin deficiency syndrome, and deficiency of qi and yin syndrome were main
      syndrome types in senile hypertension patients. There was statistical difference
      in the distribution curves of blood pressure, atherosclerosis, and age of various
      TCM syndrome types.

PMID- 24941840
TI  - [Intervention of Shenkangling Decoction on the renal injury of primary nephrotic
      syndrome children patients of Shen deficiency blood stasis syndrome: a clinical
      observation].
AB  - OBJECTIVE: To observe the intervention of Shenkangling Decoction (SD) on the
      renal injury of primary nephrotic syndrome (PNS) children patients of Shen
      deficiency blood stasis syndrome (SDBSS) and to explore its mechanism. METHODS:
      Totally 65 PNS children patients were randomly assigned to the combined group (33
      cases, treated by SD +Western medicine) and the Western medicine group (32 cases,
      treated by Western medicine). Meanwhile, 30 healthy children were recruited as
      the healthy control group from the medical examination center. Those in the
      Western medicine group were treated with prednisone (5 mg per tablet) at the
      daily dose of 1.5 -2.0 mg/kg till two weeks after their urine protein turned to
      negative. Then the dosage was reduced once daily per every other day. The
      therapeutic course lasted for more than 1 year. For those with no effect of
      prednisone or partial effect, cyclophosphamide intravenous pulse therapy was
      additionally applied for 2 successive days per week, a total of 6 times, or they
      took cyclosporine A. Patients in the combined group additionally took SD while
      starting treatment of prednisone. SD was decocted in water for oral dose, once
      daily, taken in two portions until 2 months after prednisone was discontinued.
      Efficacy was evaluated based on serum levels of chemotactic factor CXCL16,
      disintegrin metalloproteinase 10 ( ADAM10 ), disintegrin metalloproteinase 17
      (ADAM17), albumin (ALB), total cholesterol (TC), and 24-h urine protein excretion
      (UPE) detected by ELISA before and after treatment. RESULTS: Compared with before
      treatment in the same group, levels of CXCL16, ADAM10, ADAM17, TC, and 24-h UPE
      were significantly lower in the two treatment groups (P <0. 01). Compared with
      the control group, levels of CXCL16, ADAM10, ADAM17, TC, and 24-h UPE
      significantly increased, and the serum ALB level decreased in the two treatment
      groups (P <0.01). Compared with the Western medicine group at the same time
      point, levels of CXCL16, ADAM10, ADAM17, TC, and 24-h UPE significantly decreased
      in the combined group. The 1 -year recurrence rate and the recurrence times
      decreased in the combined group (P <0.01). The complete remission rate increased
      in the combined group (P <0.01). CONCLUSION: SD could effectively improve the
      clinical prognosis of PNS children patients possibly by reducing the release of
      inflammatory mediators such as CXCL16, ADAM10, and ADAM17, decreasing UPE and the
      TC level, and elevating the serum ALB level.

PMID- 24941841
TI  - [The anesthesiologic value of transcutaneous acupoint electrical stimulation
      combined with general intravenous anesthesia in endoscopic thyroidectomy
      patients: a clinical study].
AB  - OBJECTIVE: To explore the clinical anesthesia value of transcutaneous acupoint
      electrical stimulation (TAES) combined with general intravenous anesthesia in
      endoscopic bilateral thyroidectomy patients. METHODS: Totally 60 patients who
      underwent endoscopic bilateral thyroidectomy were equally randomly assigned to 2
      groups, the treatment group and the control group, 30 in each group. Patients in
      the treatment group received TAES combined general intravenous anesthesia, while
      those in the control group received total intravenous anesthesia. Anesthesia was
      maintained by target controlled infusion of propofolum combined constant speed
      infusion of remifentanil in the two groups. TAES was maintained from 30 min
      before anesthesia induction to the end of endoscopic thyroidectomy at bilateral
      Hegu (L14) and Neiguan (PC6). The mean artery pressure (MAP) and heart rate (HR)
      were recorded at different time points of anesthesia, i.e., immediately after
      entry into the operating room (TO), immediately after intubation (T1), 5 min
      after intubation (T2), 5 min before incision (T3), 5 min after incision (T4), 30
      min after inflation (T5), at the end of surgery (T6), 5 min before extubation
      (T7), immediately after extubation 0 (T8), and 5 min after extubation (T9). The
      concentration of IL-6 and TNF-alpha were measured at TO, T3, T5, and T6. The
      target concentration of propofol was also recorded at T3, T4, and T5. RESULTS:
      There was no statistical difference in the operation time between the two groups
      (P >0.05). Compared with TO in the same group, HR at T3-T4 decreased and
      increased at T8-T9, and MAP increased at T7-T9 in the treatment group; HR
      decreased at T3 and increased at T7-T9, MAP increased at T1, T5, T7-T9, and MAP
      decreased at T2-T3 in the control group. IL-6 increased at T5-T6, while TNF-alpha
      decreased at T6 in the two groups (P <0.01,P <0.05). Compared with the control
      group at the same time point, HR decreased at T6-T9, MAP decreased at T1, T4, T5,
      T7-T9, MAP increased at T3, and IL-6 decreased at T5-T6 in the treatment group (P
      <0. 05). The concentration and the total amount of propofol were significantly
      lower in the treatment group than in the control group (P <0.01,P <0.05).
      CONCLUSIONS: TAES could maintain the hemodynamics more stably and inhibit the
      stress response in endoscopic thyroidectomy. It also reduce the dosage of
      anesthetics and improve the safety of anesthesia.

PMID- 24941842
TI  - [Metabolic changes in abnormal savda patients with different types of tumor: a
      clinical observation].
AB  - OBJECTIVE: To explore in vivo metabolic changes in abnormal savda patients with
      different types of tumor. METHODS: A total of 142 abnormal savda patients with
      common cancer types were enrolled in this study, and 50 healthy volunteers were
      recruited as the control group. For each sample, the H Nuclear Magnetic Resonance
      (NMR) based metabonomic analysis was performed. The free attenuation signal was
      computed subsection integral. Data obtained were analyzed by the Orthogonal
      Partial Least-Squares Discriminant Analysis (OPLS-DA). RESULTS: Compared with the
      control group, leucine, isoleucine, valine, histidine, phenylalanine, tyrosine,
      alanine, creatine, lactic acid, inositol, alpha-and beta-glucose, unsaturated
      lipids, very low density lipoprotein (VLDL) significantly decreased (P <0.05),
      while glycoprotein and carnitine significantly increased (P <0. 05) in the
      abnormal Savda group. CONCLUSION: Abnormal savda patients with different types of
      tumor had similar metabonomics changes.

PMID- 24941844
TI  - [Effect of Modified Zhisou Powder on the lung function of chronic obstructive
      pulmonary disease model rats of northwest China cold dryness syndrome].
AB  - OBJECTIVE: To observe Modified Zhisou Powder (MZP) on the lung function of
      chronic obstructive pulmonary disease (COPD) model rats of northwest China cold
      dryness syndrome (NCCDS). METHODS: Totally 90 male Wistar rats were randomly
      divided into three groups, i.e., the normal control group (n =20), the COPD model
      group (n =35), and the COPD of NCCDS group (n =35). The COPD model was
      established by tracheal dripping porcine pancreatic elastase (PEE) in combination
      with fumigation for 90 days. The COPD of NCCDS model was set up by tracheal
      dripping PEE +fumigation + cold and dry environmental stress for 90 days. Then
      rats in the COPD of NCCDS were randomly divided into the MZP intervention group
      (n =11 )and the normal saline intervention group (n =10).All intervention lasted
      for 15 successive days. The lung function was detected using Small Animal Lung
      Function Device at day 90 and day 105. And the lung pathology was also observed.
      RESULTS: Little amount of sputum sound could be heard in the airway of the COPD
      model group and the COPD of NCCDS group. Pathological section showed alveolar
      ectasia, narrowed and broken alveolar septa, forming larger capsular space with
      infiltration of inflammatory cells. Rats in the COPD of NCCDS group showed
      chills, increased amount of drinking water, and loose stool. MZP could improve
      their symptoms. As for lung function test, compared with the normal control
      group, Te increased in the COPD model group (P <0.01), and EF50 decreased
      (P<0.05). PEF and EF50 decreased (P <0.01), Ti and Te increased (P <0.01, P
      <0.05) in the COPD of NCCDS group. Compared with the normal saline intervention
      group, PEF and EF50 increased (P < 0.01), Ti and Te decreased (P <0.01) in the
      MZP intervention group. CONCLUSION: MZP could improve the symptoms of COPD rats
      of NCCDS, and delay the velocity of decreased lung function.

PMID- 24941843
TI  - [Treatment of antipsychotics induced mild hepatic damage by Dangfei Liganning
      Tablet: an efficacy observation].
AB  - OBJECTIVE: To observe the therapeutic efficacy of Dangfei Liganning Tablet (DLT)
      in the treatment of antipsychotics induced mild hepatic damage. METHODS: Totally
      80 mental inpatients with antipsychotics induced mild liver injury were randomly
      assigned to two groups, the treatment group (40 cases) and the control group (40
      cases). Patients in the treatment group took DLT, two tablets each time, three
      times per day, while those in the control group took Liver-protecting Tablet
      (LT), four tablets each time, three times per day. The treatment course was 4
      weeks for all. Changes of glutamic-pyruvic transaminase (ALT) and glutamic
      oxalacetic transaminase (AST) were observed before treatment, week 1, 2, and 4
      after treatment. The therapeutic efficacy was compared between the two groups.
      RESULTS: Compared with the former time point, ALT and AST gradually decreased in
      the two groups at week 1, 2, and 4 (P <0. 05). The cured rate was 72. 5% and the
      total effective rate was 97. 5% in the treatment group. They were 62. 5% and 90.
      0% respectively in the control group. There was no statistical difference in the
      two indices between the two group (P >0.05). No obvious adverse reaction occurred
      in the two groups. CONCLUSION: DLT could treat antipsychotics induced mild
      hepatic damage in a safe and effective way.

PMID- 24941845
TI  - [Effect of Yishen Daluo Decoction on the expression of PLP, Olig1, and Olig2 in
      mice with experimental autoimmune encephalomyelitis].
AB  - OBJECTIVE: To study the effect of Yishen Daluo Decoction (YDD) on the expression
      of protein lipoprotein (PLP), oligodendrocyte transcription factor 1 (Olig 1),
      and oligodendrocyte transcription factor 2 (Olig2) in mice with experimental
      autoimmune encephalomyelitis (EAE). METHODS: Totally 40 mice were randomly
      divided into 4 groups, i.e., the normal group, the model group, the Chinese
      medicine (CM) group, and the Western medicine (WM) group, 10 mice in each group.
      Each mouse in the model, CM, and WM groups was subcutaneously injected with 200
      microL antigen emulsion (containing 150 micro g PLP139 -151 and 400 micro g
      H37RA) in two parts at the upper abdomen on the first day. 100 microLBordetella
      pertussis juice (containing 0. 6 x 10(6) Bordetella pertussis) was injected by
      caudal vein on the first and the third day. On the 7th day after modeling, each
      mouse in the normal group and the model group was intragastrically given normal
      saline (0. 1 mL/10 g). YDD (0. 2 g crude drug/10 g) was intragastrically given to
      mice in the CM group, and prednisone (0. 039 mg/10 g) was intragastrically given
      to mice in the WM group. All mice were intervened for 54 days. Changes of PLP,
      Olig1, and Olig2 in the brain tissue of EAE mice were detected by Western blot.
      Results The levels of PLP and Olig2 in the brain tissue of the model group were
      less than those of the normal group (P <0.05). Compared with the model group, the
      levels of PLP, Olig1, and Olig2 in the brain tissue increased in the CM group (P
      <0.05); the levels of PLP and Olig2 in the brain tissue increased in the WM group
      (P <0.05). Compared with the WM group, the level of Olig1 in the brain tissue
      increased in the CM group (P <0.05). CONCLUSION: YDD could enhance remyelination
      by elevating the levels of Olig1 and Olig2 in the brain tissue of EAE mice.

PMID- 24941846
TI  - [Astragalus polysaccharides improved the cardiac function in Sjogren's syndrome
      model rats based on keap 1-Nrf2/ARE signaling pathway: a mechanism exploration].
AB  - OBJECTIVE: To explore the mechanism of Astragalus polysaccharides (APS) for
      improving the cardiac function of Sjogren's syndrome (SS) model rats based on
      Keapl-Nrf2/ARE signaling pathway. METHODS: Totally 48 male Wistar rats were
      randomly divided into four groups by random digit table, i.e., the blank control
      group,the model control group,the APS group, and the hydroxychloroquine group, 12
      in each group. Except those in the blank control group, 0. 1 mL mixed antigen
      protein of sufficiently emulsified Freund's complete adjuvant and submandibular
      gland protein was injected from two feet plantar to induce SS model. The
      intervention was started from 19th day after inflammation induction. Equal volume
      of normal saline was given to rats in the blank control group (1 mL/100 g), APS
      was administered to those in the APS group (1 mg/100 g), and hydroxychloroquine
      (0.03 125 g/kg) was administered to those in the hydroxychloroquine group. All
      rats were intervened once per day for 30 consecutive days. Changes of rats' body
      mass and drinking water quantity, submandibular gland index, spleen index,
      histological changes of glands were observed. Changes of the heart function were
      monitored using invasive hemodynamics. Serum reactive oxygen species (ROS),
      malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity
      (TAC), tumor necrosis factor alpha (TNF-alpha), and interleukin-35 (IL-35)were
      detected using ELISA method. The pathological changes were observed using HE
      staining. The protein expression of ROS, reactive nitrogen species (RNS),
      glutathione (GSH), and thioredoxin (TRX) were observed by immunohistochemical
      staining. The mRNA expression of Keap1, Nrf2, and ARE was detected using real
      time fluorescent quantitative PCR. The protein expression levels of gamma
      glutamic acid and a half long glycine synthetase (gamma-GCS) and heme oxygenase 1
      (HO-1) in the myocardial tissue were determined by Western blot method. Results
      Compared with the blank control group, the quantity of drinking water,
      submandibular gland index, spleen index, heart rate (HR), cardiac index (HI),
      left ventricular systolic pressure (LVSP), left ventricular diastolic pressure
      (LVEDP), MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression,
      Keap 1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1
      protein expression, and gamma-GCS protein expression significantly increased (P
      <0.01); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH, and TRX significantly
      decreased (P <0.01) in the model group. Compared with the model group, the
      quantity of drinking water, submandibular gland index, spleen index, LVEDP, MDA,
      ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap1 mRNA
      expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein
      expression, and gamma-GCS protein expression significantly decreased (P<0.05);
      body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH protein expression, and TRX protein
      expression significantly increased (P < 0.05, P <0.01) in the AR group and the
      hydroxychloroquine group. In the hydroxychloroquine group HR increased (P <0.05).
      In the AR group HR and LVSP decreased (P <0. 05, P <0. 01). Compared with the
      hydroxychloroquine group, HR, LVEDP, - dp/dtmax, y-GCS protein expression
      significantly decreased (P <0. 05, P <0. 01); SOD, TAC, GSH, TRX, HO-1 protein
      expression increased (P <0.01 )in the AR group. HI was positively correlated with
      ROS (P <0. 05). LVSP and LVEDP were positively correlated with Keap1 -Nrf2/ARE
      signaling pathways (P <0. 01) , and negatively correlated with TAC (P <0. 05, P
      <0. 01 ). +/-dp/dtmax was negatively correlated with Keap1-Nrf2/ARE signaling
      pathways(P <0.05), and positively correlated with TNF alpha (P <0. 05).
      CONCLUSIONS: Declined heart function exists in SS rats. The mechamechanism of APS
      for improving the heart function might be closely correlated with activating
      Keap1-Nrf2/ARE signaling pathway.

PMID- 24941847
TI  - [Effect of American Ginseng Capsule on the liver oxidative injury and the Nrf2
      protein expression in rats exposed by electromagnetic radiation of frequency of
      cell phone].
AB  - OBJECTIVE: To observe the effect of American Ginseng Capsule (AGC) on the liver
      oxidative injury and the Nrf2 protein expression in the liver tissue of rats
      exposed by 900 MHz cell phone electromagnetic radiation. METHODS: Totally 40 male
      SD rats were randomly divided into the normal control group, the model group, the
      Shuifei Jibin Capsule (SJC) group, and the AGC group,10 in each group. Rats in
      the normal control group were not irradiated. Rats in the rest three groups were
      exposed by imitated 900 MHz cellular phone for 4 h in 12 consecutive days.
      Meanwhile, rats in the SJC group and the AGC group were intragastrically
      administrated with suspension of SJC and AGC (1 mL/200 g body weight)
      respectively. Normal saline was administered to rats in the normal control group
      and the model group. The histolomorphological changes of the liver tissue were
      observed by HE staining. Contents of malonic dialdehyde (MDA), superoxide
      dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX)were
      detected by colorimetry. The Nrf2 protein expression of hepatocytes was detected
      by immunohistochemical assay and Western blot. RESULTS: Compared with the normal
      control group, hepatocyte nucleus was atrophied or partially disappeared, the
      contents of liver MDA and Nrf2 protein obviously increased (P <0. 05, P <0. 01);
      contents of liver SOD and GSH decreased (P <0. 05) in the model group. Compared
      with the model group, karyopyknosis was obviously attenuated and approached to
      the normal level in the SJC group and the AGC group. The contents of liver MDA
      and Nrf2 protein expression decreased (P <0. 05), and the contents of liver SOD,
      GSH, and GSH-PX obviously increased (P < 0.05) in the SJC group. The contents of
      liver MDA and the Nrf2 protein expression decreased (P < 0.05), and contents of
      SOD and GSH obviously increased in the AGC group (P <0.01, P <0.05). CONCLUSIONS:
      The electromagnetic radiation induced by 900 MHz cell phone could affect the
      expression of Nrf2 protein, induce oxidative injury, and induce abnormal
      morphology of liver cells. SJC and AGC could promote the morphological recovery
      of the liver cells. Its mechanism might be related to affecting the expression of
      Nrf2 protein and attenuating oxidative damage of liver cells.

PMID- 24941848
TI  - [Study on the mechanism of polypeptide extract from scorpion venom on inhibition
      of angiogenesis of H 22 hepatoma].
AB  - OBJECTIVE: To explore the mechanism of polypeptide extract from scorpion venom
      (PESV) on inhibiting angiogenesis. METHODS: The H22 hepatoma tumor model was
      established by subcutaneously implanting H22 hepatoma cells into mice. The tumor
      bearing mice were randomly divided into 4 groups, i.e., the control group, the
      high dose PESV group, the low dose PESV group, and the 5-fluorouracil (5-Fu)
      group, 10 mice in each group. The intervention was lasted for 14 days. The growth
      curve of the tumor volume was drawn and the inhibition rate calculated.
      Pathological changes of the tumors were observed by HE staining. The microvessel
      density (MVD) was detected using SP method. The protein expression levels of
      phosphatidylinositol 3-kinase (P13K), phosphoprotein kinase B (P-Akt), hypoxia
      inducible factor-1 alpha (HIF-1 )alpha, and vascular endothelial growth factor-A
      (VEGF-A) were detected by immunohistochemical assay and Western blot. RESULTS:
      The tumor inhibitory rate was 64.8%, 43.7%, and 32.4% in the 5-Fu group, the high
      dose PESV group, and the low dose PESV group. Compared with the control group,
      the protein expression of PI3K, P-Akt, HIF-1alpha, and VEGF-A were obviously
      inhibited by PESV and 5-Fu (P <0. 05,P <0. 01). The MVD also decreased in the
      high and low dose PESV groups (P < 0.05). CONCLUSIONS: PESV could inhibit the
      angiogenesis of H22 hepatoma. The mechanisms might be associated with suppressing
      the expression of PI3K, P-Akt, HIF-1 alpha, and VEGF-A.

PMID- 24941849
TI  - [Intervention effect of Dachengqi Granule on apoptosis of small intestine smooth
      muscle cells in rats with multiple organ dysfunction syndrome].
AB  - OBJECTIVE: To observe the intervention of Dachengqi Granule (DG) on the apoptosis
      of small intestine smooth muscle cells (SMCs) in rats with multiple organ
      dysfunction syndrome (MODS) and its mechanisms. METHODS: Healthy 100 adult Wistar
      rats were randomly divided into the control group (n =20), the MODS model group
      (n =40), and the DG group (n =40).E. coli suspension was peritoneally injected to
      rats in the model group and the DG group to establish bacterial peritonitis
      induced MODS model. DG at 1 mL/100 g was administered by gastrogavage to rats of
      the DG group, twice daily for 3 successive days. Twenty-four hours after
      modeling, the proximal segment of intestine was taken and stained by using
      terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and
      immunohistochemistry. Changes of apoptosis quantity of SMCs and the expression of
      Bcl-2 associated X protein (Bax), B cell lymphoma/leukemia-2 (Bcl-2) and
      cytochrome c protein (Cyt c) in mitochondrial apoptotic signaling pathway were
      observed. RESULTS: Compared with the control group, the apoptosis quantity of
      SMCs and the expression of Bax and Cyt c protein significantly increased, and the
      expression of Bcl-2 protein significantly decreased in the MODS model group (P
      <0.01). Compared with the MODS model group, the apoptosis quantity of SMCs and
      the expression of Bax and Cyt c proteins significantly decreased, and the
      expression of Bcl-2 protein significantly increased in the DG group (allP <0.01).
      CONCLUSION: DG could inhibit apoptosis of SMCs through suppressing activation of
      mitochondrial apoptotic signaling pathway in intestinal SMCs, thus promoting the
      recovery of the gastrointestinal motility function in rats with MODS.

PMID- 24941850
TI  - [Inhibitory effect of Xiaotan Sanjie Recipe on the microsatellite instability of
      orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice].
AB  - OBJECTIVE: To study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the
      microsatellite instability of orthotopic transplantation tumor in MKN-45 human
      gastric cancer nude mice. METHODS: The 3rd passage subcutaneous transplantation
      tumor was taken as the origin of the model by using MKN-45 human gastric cancer
      cell lines. MKN-45 human gastric cancer nude mouse model was established using OB
      glue adhesive method. Then 30 nude mice were divided into the model group, the
      XSR group, and the chemotherapy group. Mice in the XSR group were
      intragastrically given XSR at the daily dose of 0.4 mL. Mice in the chemotherapy
      group were intragastrically given Fluorouracil at the daily dose of 0.4 mL. No
      intervention was given to mice in the model group. After 6 weeks of medication,
      the tumor weight was measured, and the tumor inhibition rate calculated. The
      size, the peak height, and the peak area of 5 microsatellite instability sites
      were detected. RESULTS: The tumor inhibition rate was 40. 84% in the XSR group.
      The tumor weight was significantly lower in the XSR group than in the model group
      (P < 0.01), showing no statistical difference when compared with the chemotherapy
      group (P >0.05). The incidence of high microsatellite instability (MSI-H) in the
      model group was 70%, and the incidence of low microsatellite instability (MSI-L)
      was 30%. Microsatellite stable site tended be stable after 6 weeks of XSR
      treatment. CONCLUSION: XSR showed inhibition on microsatellite instable
      orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.

PMID- 24941851
TI  - [Effect of Jiangang Yishen Recipe on high insulin induced cell proliferation of
      human glomerular mesangial cells and the expression of insulin receptor substrate
      1 and phosphatidylinositol-3-kinase].
AB  - OBJECTIVE: To investigate the effect of Jiangtang Yishen Recipe (JTYSR) on high
      insulin induced cell proliferation of human glomerular mesangial cells (HMCs) and
      the expression of insulin receptor substrate 1 (IRS-1) and phosphatidylinositol-3
      kinase (PI-3K). METHODS: HMCs were divided into 4 groups, i.e., the negative
      control group, the high insulin model group, the JTYSR group, and the LY294002
      group. The concentration of insulin, JTYSR, and LY294002 was respectively
      confirmed by pre-experiment. Different culture solution was respectively added
      for different groups. RPMI1640 culture solution was added for HMCs in the
      negative control group, while HMCs in the rest 3 groups were cultured by 100
      nmol/L insulin for 24 h. Meanwhile, HMCs from the JTYSR group and the LY294002
      group were exposed to 125 mg/L JTYSR and 80 micromol/L LY294002 respectively for
      further 48 h. The proliferation of HMCs was detected by MTT and flow cytometry.
      The protein expression of IRS-1 and PI-3K in HMC was detected by
      immunohistochemical assay and Western blot. Results The proliferation of HMCs
      induced by high insulin could be significantly lowered, and the protein
      expression of IRS-1 and PI-3K could be down-regulated in the JTYSR group and the
      LY294002 group (P <0.01). Compared with the LY294002 group, the protein
      expression of IRS-1 and PI-3K could be slightly down-regulated in the JTYSR group
      (P <0.05). CONCLUSION: JTYSR could lower high insulin induced proliferation of
      HMCs, and its mechanism might be related to insulin signaling pathway.

PMID- 24941852
TI  - [Effect of Yijing Recipe on apoptosis of testis spermatogenic cells and the
      expression of Bcl-2 and Bax protein in infertility rats].
AB  - OBJECTIVE: To observe the effect of Yijing Recipe (YR) on the apoptosis of testis
      spermatogenic cells and the protein expression of Bcl-2/Bax in rats with adenine
      induced infertility. METHODS: Totally 75 Wistar rats were randomly divided into 5
      groups, i.e., the blank control group, the model group, the high dose YR group,
      the middle dose YR group, and the low dose YR group, 15 in each group. Except
      those in the blank control group, rats in the rest groups were intragastrically
      administered with adenine for 10 successive days. From the 11th day, rats in the
      blank control group and the model group were fed with equal volume of normal
      saline. Rats in the YR groups were intragastrically administered with YR at
      different doses (3.38 g/100 g; 1.69 g/100 g; 0.85 g/100 g), once daily for 20
      consecutive days. All rats were killed by the end of the experiment and their
      testes extracted. The apoptosis of spermatogenic cells and the expression of Bcl
      2/Bax proteins were detected by terminal deoxynucleotidyl transferase-mediated
      biotinylated UTP nick end labeling (TUNEL) and SABC method. RESULTS: Compared
      with the blank control group, the Bcl-2 protein expression decreased, the Bax
      protein expression increased, and the apoptosis index increased in the model
      group, showing statistical difference (P <0.01). Compared with the model group,
      the Bcl-2 protein expression increased in the three YR treated groups (P <0.01, P
      <0.05). The Bax protein expression level decreased in the high and middle dose YR
      groups (P <0. 01, P <0. 05). The apoptosis index decreased in the middle dose YR
      group (P <0.01). CONCLUSION: YR could inhibit the apoptosis of spermatogenic
      cells through regulating the expression of Bcl-2 and Bax protein in the testis.

PMID- 24941854
TI  - [Thinking on the junction point of Chinese medicine in comparative effectiveness
      research on chronic obstructive pulmonary disease].
AB  - In this paper, we described basic connotations of comparative effectiveness
      research (CER), expounded the application of CER in chronic obstructive pulmonary
      disease (COPD). In addition, on the basis of research practice of Chinese medical
      treatment for COPD in recent years, we put forward the thought of the junction
      point of Chinese medicine in CER on COPD from the perspective in screening
      effective Chinese herbs, establishing treatment program/methods/technologies, and
      outcomes evaluation.

PMID- 24941855
TI  - [Experience of the prevention and treatment of bronchial asthma by integrative
      medicine].

PMID- 24941853
TI  - [Screening active components in compound danshen based on PXR-CYP3A4: an
      experimental study].
AB  - OBJECTIVE: To screen active components in Compound Danshen (CD) based on pregnane
      X receptor-cytochrome P450 3A4 (PXR-CYP3A4). METHODS: By using PXR-CYP3A stable
      transfection human hepatoblastoma G2 (HepG2) cell lines engineering cell strain
      combined reporter genes technology, active components that induce or inhibit PXR
      CYP3A4 paths in CD were screened, and confirmed at the level of enzymic
      activities. The experiment was divided into the positive control group (RIF 10
      micro mol/L), the DMSO group (DMSO 0.1%), each dose of treatment groups
      (ginsenoside Rc, Rf, Rb2, Rg2, F2, F1, tanshinone I , isoborneol 5, 10, 25, 50,
      100, and 200 micro mol/L; each with six duplicates). Cells medium was removed 36,
      48, and 60 h after treatment. The activity of CYP3A4 was then determined in the
      supernant and the fold induction was calculated. RESULTS: Compared with the DMSO
      group, the fold induction increased when ginsenoside Rc, Rf, Rb2, Rg2, F2, F1,
      tanshinone I , and isoborneol 50 and 100 micro mol/L was respectively intervened
      for 36, 48, and 60 h (P <0.05). When cells were treated with isoborneol 200 micro
      mol/L for 48 and 60 h,the fold induction of ginsenoside Rb2, Rg2, and F1 was
      significantly higher than that of the RIF group (P <0.05). Enzymic activity
      results showed that ginsenoside Rc, Rf, Rb2, F2, and F1 could increase the enzyme
      activity of CYP3A4 at 48 h (P <0.05). CONCLUSION: Ginsenoside Rc, Rf, Rb2, F2,
      F1, tanshinone I, and isoborneol in DC could induce CYP3A4 enzymes.

PMID- 24941856
TI  - [Clinical experience of Dr. Huang Shi-lin in diagnosing and treating immune
      thrombocytopenia].

PMID- 24941857
TI  - [Framework analysis method in qualitative research].
AB  - In recent years a number of qualitative research methods have gained popularity
      within the health care arena. Despite this popularity, different qualitative
      analysis methods pose many challenges to most researchers. The present paper
      responds to the needs expressed by recent Chinese medicine researches. The
      present paper is mainly focused on the concepts, nature, application of framework
      analysis, especially on how to use it, in such a way to assist the newcomer of
      Chinese medicine researchers to engage with the methodology.

PMID- 24941858
TI  - [Correspondence analysis of chinese medical constitution features in different
      ages population].
AB  - OBJECTIVE: To explore the distribution features of Chinese medical constitutions
      in different ages population, thus providing scientific evidence of constitution
      process theory. METHODS: Recruited were 21 948 cases from a survey of Chinese
      medical constitutions and health conditions in 9 provinces or municipalities
      across China (including Jiangsu, Anhui, Gansu, Qinghai, Fujian, Beijing, Jilin,
      Jiangxi, and Henan) from Dec 2005 to Jan 2007. The body constitution type of
      individual was diagnosed using discriminant analysis on the basis of Chinese
      medical constitution questionnaire. By using correspondence analysis, the
      correlation between the general population, genders, ages, and Chinese medical
      constitution types was studied. RESULTS: Constitutions of yin-deficiency type,
      wetness-heat type, qi-depression type, and special diathesis type often occurred
      in the population ranging 15 -24 years old. Gentleness type mostly occurred in
      the population ranging 25 -44 years old. During this time period, phlegm-wetness
      type and wetness-heat type were liable to occur in males, while blood-stasis type
      was liable to occur in females. Qi-deficiency type and yang-deficiency type were
      most often seen in those older than 45 years. Phlegm-wetness type and blood
      stasis type body constitution were also liable to occur in those older than 45
      years. CONCLUSIONS: The distribution features were different in different Chinese
      medical constitutions. Different constitution types exist in different genders.
      Different constitution types exist different ages population.

PMID- 24941859
TI  - [One case report of treating Kikuchi disease by Yinqiao powder].

PMID- 24941860
TI  - [Research of preventing and treating respiratory virus infections by Chinese
      medicine: a review].

PMID- 24941861
TI  - [Progressing of treating hypertension patients accompanied with insulin
      resistance by Shen-supplementing Chinese drugs].

PMID- 24941862
TI  - Comparison of the response to phosphorus deficiency in two lupin species, Lupinus
      albus and L. angustifolius, with contrasting root morphology.
AB  - White lupin (Lupinus albus) produces cluster roots, an adaptation to low soil
      phosphorus (P). Cluster roots exude large levels of P-solubilizing compounds such
      as citrate and malate. In contrast, narrow leaf lupin (L. angustifolius) is
      closely related to L. albus, but does not produce cluster roots. To examine the
      different strategies for P acquisition, we compared the growth, biomass
      allocation, respiratory properties and construction cost between L. albus and L.
      angustifolius under P-deficient conditions. Both Lupinus species were grown in
      hydroponic culture with 1 or 100 MUM P. Under the P-deficient regime, L. albus
      produced cluster roots with little change in biomass allocation, while L.
      angustifolius significantly increased biomass allocation to roots. The rate of
      cyanide-resistant SHAM (salicylhydroxamic acid)-sensitive respiration was high in
      cluster roots and very low in roots of L. angustifolius. These results suggest a
      low alternative oxidase (AOX) activity in L. angustifolius roots, and thus, ATP
      would be produced efficiently in L. angustifolius roots. The construction cost
      was highest in cluster roots and lowest in L. angustifolius roots. This study
      shows that under P deficiency, L. albus produces high-cost cluster roots to
      increase the P availability, while L. angustifolius produces large quantities of
      low-cost roots to enhance P uptake. 

PMID- 24941863
TI  - Characteristics and coinfection with syphilis in newly HIV-infected patients at
      the University Hospital Dresden 1987-2012.
AB  - BACKGROUND: In Germany, notification data cannot be used to determine HIV and
      syphilis coinfection. No regional cohort has been studied for this in Eastern
      Germany. The rising incidence of syphilis from 2010 to 2012, predominantly in men
      having sex with men (MSM), has been suggested as a cause for recent increases in
      HIV infection rates in this group. PATIENTS AND METHODS: Characteristics of 355
      consecutive patients newly diagnosed with HIV infection at the University
      Hospital Dresden 1987-2012 were retrospectively compared to German surveillance
      data from the region of Dresden. Additionally, coinfection with syphilis was
      determined. RESULTS: Compared to German surveillance data, we observed higher
      proportions of persons originating from high prevalence countries and of AIDS
      cases. In the age group of up to 25 years, the proportion of MSM has risen 3-fold
      since 2001. At time of HIV diagnosis, seroprevalence of syphilis was 20.3 %.
      Active syphilis (VDRL >= 1: 8) occurred in 6.7 % of patients, predominantly MSM,
      who also exhibited a significantly higher HIV viral load. CONCLUSIONS: Our
      findings suggest a causative relationship between recently rising incidences of
      syphilis and HIV infection in MSM. Early diagnosis of syphilis may promote
      earlier diagnosis of HIV infection; therefore, HIV prevention measures should
      also include other sexually transmitted infections.

PMID- 24941864
TI  - The effects of age and emotional valence on recognition memory: an ex-Gaussian
      components analysis.
AB  - The aim of this work was to study the effects of valence and age on visual image
      recognition memory. The International Affective Picture System (IAPS) battery was
      used, and response time data were analyzed using analysis of variance, as well as
      an ex-Gaussian fit method. Older participants were slower and more variable in
      their reaction times. Response times were longer for negative valence pictures,
      however this was statistically significant only for young participants. This
      suggests that negative emotional valence has a strong effect on recognition
      memory in young but not in old participants. The tau parameter, often related to
      attention in the literature, was smaller for young than old participants in an ex
      Gaussian fit. Differences on the tau parameter might suggest poorer attentional
      performance in old participants. 

PMID- 24941865
TI  - Late-life depression and quality of life in a geriatric evaluation and management
      unit: an exploratory study.
AB  - BACKGROUND: Late-life depression is common among elderly patients. Ignorance of
      the health problem, either because of under-diagnosis or under-treatment, causes
      additional medical cost and comorbidity. For a better health and quality of life
      (QoL), evaluation, prevention and treatment of late-life depression in elderly
      patients is essential. METHODS: This study examined (1) the differences of
      clinical characteristics, degree of improvement on QoL and functionality on
      discharge between non-depressed and depressed elderly inpatients and (2) factors
      associated with QoL on discharge. Four hundred and seventy-one elderly inpatients
      admitted to a geriatric evaluation and management unit (GEMU) from 2009 to 2010
      were enrolled in this study. Comprehensive geriatric assessment including the
      activities of daily living (ADL), geriatric depression scale, and mini-mental
      state examination were conducted. QoL was assessed using the European Quality of
      Life-5 Dimensions and the European Quality of Life-5 Dimensions Visual Analog
      Scale on discharge. Information on hospital stay and Charlson comorbidity index
      were obtained by chart review. Chi-square tests, independent t-tests, Mann
      Whitney U tests and multiple linear regressions were used in statistical
      analysis. RESULTS: Worse QoL and ADL on discharge were found among the depressed.
      Depressive symptoms, female gender, duration of hospital stay, and rehabilitation
      were significant factors affecting QoL on discharge in linear regression models.
      CONCLUSIONS: The importance of the diagnosis and treatment of depression among
      elderly inpatients should not be overlooked during hospital stay and after
      discharge. Greater efforts should be made to improve intervention with depressed
      elderly inpatients.

PMID- 24941866
TI  - Future pharmaceutical research: the need to look beyond science.

PMID- 24941867
TI  - Modeling hepatic drug metabolism and toxicity: where are we heading?

PMID- 24941868
TI  - What is the potential of G protein-coupled receptor [corrected] allosteric sites
      in drug design?

PMID- 24941869
TI  - News & Analysis: new initiative aims to improve success of early stage drug
      discovery.

PMID- 24941870
TI  - Selective and potent small-molecule inhibitors of PI3Ks.
AB  - Class I PI3Ks are composed of four catalytic subunit variants (p110alpha,
      p110beta, p110delta and p110gamma). The PI3K pathway is among the most frequently
      activated pathways in many diseases, and has emerged as an attractive target for
      drug development, in particular for the treatment of many human cancers including
      breast, prostate, ovarian, gastric, colon and hepatocellular cancers. One of the
      challenges in the discovery of drugs that target kinases is designing small
      molecule inhibitors that are sufficiently selective to minimize off-target
      activity and reduce the risk of potential toxicity. This review explores the
      current landscape of PI3K-selective inhibitor development and highlights recent
      advances in achieving selectivity for PI3Ks over other protein kinases, with an
      emphasis on available structural information. 

PMID- 24941871
TI  - From neuraminidase inhibitors to conjugates: a step towards better anti-influenza
      drugs?
AB  - For the treatment of seasonal flu and possible pandemic infections the
      development of new anti-influenza drugs that have good bioavailability against a
      broad spectrum of influenza viruses including the resistant strains is needed. In
      this review, we summarize previous methods for the structural modification of
      zanamivir, a potent neuraminidase inhibitor that has rare drug resistance, in
      order to develop effective anti-influenza drugs. We also report recent research
      into the design of multivalent zanamivir drugs and bifunctional zanamivir
      conjugates, some of which have shown better efficacy in animal experiments. As a
      step towards developing improved antivirals, conjugating anti-influenza drugs
      with anti-inflammatory agents can improve oral bioavailability and also exert
      synergistic effect in influenza therapy. 

PMID- 24941872
TI  - The translocator protein as a potential molecular target for improved treatment
      efficacy in photodynamic therapy.
AB  - Since its serendipitous discovery over 30 years ago, the translocator protein (18
      kDa) has been demonstrated to play an important role in a multitude of critical
      biological processes. Although implemented as a novel therapeutic and diagnostic
      tool for a variety of disease states, its most promising role is as a molecular
      target for anticancer treatments such as photodynamic therapy (PDT). This review
      gives an overview of the attempts made by researchers to design porphyrin-based
      photosensitizers for use as anticancer therapeutics in PDT as well as improved
      imaging agents for diagnostic purposes. With a better understanding of the
      structure and function of the translocator protein, the synthesis of porphyrins
      for use in PDT with optimum binding affinities will become ever more possible. 

PMID- 24941873
TI  - Novel DPP-4 inhibitors against diabetes.
AB  - DPP-4 specifically degrades the incretin hormone GLP-1 and GIP, both of which are
      vital modulators of blood glucose homeostasis. Attributed to its potential
      biological function, DPP-4 inhibition has presently represented an attractive
      therapeutic strategy for treating diabetes and aroused a significant interest in
      the pharmaceutical industry. Chemical stability, selectivity and pharmacokinetic
      properties have been continuously emphasized during the long journey of R&D
      centered on DPP-4 inhibitors. The current landscape of the development of DPP-4
      inhibitors is outlined in this review, with a focus on rational drug design and
      structural optimization to pursue chemical stability, selectivity and favorable
      pharmacokinetic properties. In addition, the structure-activity relationships,
      based on reported DPP-4 inhibitors, will be discussed. 

PMID- 24941875
TI  - Enhancing vascular relaxing effects of nitric oxide-donor ruthenium complexes.
AB  - Ruthenium-derived complexes have emerged as new nitric oxide (NO) donors that may
      help circumvent the NO deficiency that impairs vasodilation. NO in vessels can be
      produced by the endothelial cells and/or released by NO donors. NO interacts with
      soluble guanylyl-cyclase to produce cGMP to activate the kinase-G pathway. As a
      result, conductance arteries, veins and resistance arteries dilate, whereas the
      cytosolic Ca(2+) levels in the smooth muscle cells decrease. NO also reacts with
      oxygen or the superoxide anion, to generate reactive oxygen species that modulate
      NO-induced vasodilation. In this article, we focus on NO production by NO
      synthase and discuss the vascular changes taking place during hypertension
      originating from endothelial dysfunction. We will describe how the NO released
      from ruthenium-derived complexes enhances the vascular effects arising from
      failed NO generation or lack of NO bioavailability. In addition, how ruthenium
      derived NO donors induce the hypotensive effect by vasodilation is also
      discussed. 

PMID- 24941874
TI  - The identification of high-affinity G protein-coupled receptor ligands from large
      combinatorial libraries using multicolor quantum dot-labeled cell-based
      screening.
AB  - G protein-coupled receptors (GPCRs), which are involved in virtually every
      biological process, constitute the largest family of transmembrane receptors.
      Many top-selling and newly approved drugs target GPCRs. In this review, we aim to
      recapitulate efforts and progress in combinatorial library-assisted GPCR ligand
      discovery, particularly focusing on one-bead-one-compound library synthesis and
      quantum dot-labeled cell-based assays, which both effectively enhance the rapid
      identification of GPCR ligands with higher affinity and specificity. 

PMID- 24941876
TI  - Chronic air pollution and social deprivation as modifiers of the association
      between high temperature and daily mortality.
AB  - BACKGROUND: Heat and air pollution are both associated with increases in
      mortality. However, the interactive effect of temperature and air pollution on
      mortality remains unsettled. Similarly, the relationship between air pollution,
      air temperature, and social deprivation has never been explored. METHODS: We used
      daily mortality data from 2004 to 2009, daily mean temperature variables and
      relative humidity, for Paris, France. Estimates of chronic exposure to air
      pollution and social deprivation at a small spatial scale were calculated and
      split into three strata. We developed a stratified Poisson regression models to
      assess daily temperature and mortality associations, and tested the heterogeneity
      of the regression coefficients of the different strata. Deaths due to ambient
      temperature were calculated from attributable fractions and mortality rates were
      estimated. RESULTS: We found that chronic air pollution exposure and social
      deprivation are effect modifiers of the association between daily temperature and
      mortality. We found a potential interactive effect between social deprivation and
      chronic exposure with regards to air pollution in the mortality-temperature
      relationship. CONCLUSION: Our results may have implications in considering
      chronically polluted areas as vulnerable in heat action plans and in the long
      term measures to reduce the burden of heat stress especially in the context of
      climate change.

PMID- 24941877
TI  - Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole.
AB  - BACKGROUND: Appendage regeneration in amphibians is regulated by the
      combinatorial actions of signaling molecules. The requirement of molecules
      secreted from specific tissues is reflected by the observation that the whole
      process of regeneration can be inhibited if a certain tissue is removed from the
      amputated stump. Interestingly, urodeles and anurans show different tissue
      dependencies during tail regeneration. The spinal cord is essential for tail
      regeneration in urodele but not in anuran larva, whereas the notochord but not
      the spinal cord is essential for tail regeneration in anuran tadpoles. Sonic
      hedgehog is one of the signaling molecules responsible for such phenomenon in
      axolotl, as hedgehog signaling is essential for overall tail regeneration and
      sonic hedgehog is exclusively expressed in the spinal cord. In order to know
      whether hedgehog signaling is involved in the molecular mechanism underlying the
      inconsistent tissue dependency for tail regeneration between anurans and
      urodeles, we investigated expression of hedgehog signal-related genes in the
      regenerating tail of Xenopus tadpole and examined the effect of the hedgehog
      signal inhibitor, cyclopamine, on the tail regeneration. RESULTS: In Xenopus,
      sonic hedgehog is expressed exclusively in the notochord but not in the spinal
      cord of the regenerate. Overall regeneration was severely impaired in cyclopamine
      treated tadpoles. Notochord maturation in the regenerate, including cell
      alignment and vacuolation, and myofiber formation were inhibited. Proliferation
      of spinal cord cells in the neural ampulla and of mesenchymal cells was also
      impaired. CONCLUSION: As in the axolotl, hedgehog signaling is required for
      multiple steps in tail regeneration in the Xenopus tadpole, although the location
      of the Shh source is quite different between the two species. This difference in
      Shh localization is the likely basis for the differing tissue requirement for
      tail regeneration between urodeles and anurans.

PMID- 24941878
TI  - Role of casual contacts in the recent transmission of tuberculosis in settings
      with high disease burden.
AB  - Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. It
      is expected that combining multiple molecular methods will further help in
      focusing contact investigations. We performed a population-based molecular
      epidemiological study in six sites in China between 1 June 2009 and 31 December
      2010. A genotyping method combining 7-loci MIRU-VNTR and IS6110-based RFLP was
      employed to determine predictors of recent transmission. A second interview was
      performed with the clustered patients to identify potential epidemiological
      links. The molecular clustering analysis revealed that 187 isolates (15.3%) were
      clustered by sharing identical VNTR-IS6110 combined patterns, with an estimated
      recent transmission index being 8.9%. None of these patients reported having
      contacts with other members within the same cluster. Nineteen of 121 reported
      having a history of contact with a TB case within 2 years before the current TB
      diagnosis. Additionally, geographical correlation was established for 19 cases in
      nine clusters, while only one possible epidemiological link was established in
      secondary interview. The results underscore the role of casual contact or
      reactivation of latent TB as a driving factor maintaining the current endemicity
      in rural China, with high disease burdens of tuberculosis. 

PMID- 24941879
TI  - The powdery mildew resistance protein RPW8.2 is carried on VAMP721/722 vesicles
      to the extrahaustorial membrane of haustorial complexes.
AB  - Plants employ multiple cell-autonomous defense mechanisms to impede pathogenesis
      of microbial intruders. Previously we identified an exocytosis defense mechanism
      in Arabidopsis against pathogenic powdery mildew fungi. This pre-invasive defense
      mechanism depends on the formation of ternary protein complexes consisting of the
      plasma membrane-localized PEN1 syntaxin, the adaptor protein SNAP33 and closely
      sequence-related vesicle-resident VAMP721 or VAMP722 proteins. The Arabidopsis
      thaliana resistance to powdery mildew 8.2 protein (RPW8.2) confers disease
      resistance against powdery mildews upon fungal entry into host cells and is
      specifically targeted to the extrahaustorial membrane (EHM), which envelops the
      haustorial complex of the fungus. However, the secretory machinery involved in
      trafficking RPW8.2 to the EHM is unknown. Here we report that RPW8.2 is
      transiently located on VAMP721/722 vesicles, and later incorporated into the EHM
      of mature haustoria. Resistance activity of RPW8.2 against the powdery mildew
      Golovinomyces orontii is greatly diminished in the absence of VAMP721 but only
      slightly so in the absence of VAMP722. Consistent with this result, trafficking
      of RPW8.2 to the EHM is delayed in the absence of VAMP721. These findings
      implicate VAMP721/722 vesicles as key components of the secretory machinery for
      carrying RPW8.2 to the plant-fungal interface. Quantitative fluorescence recovery
      after photobleaching suggests that vesicle-mediated trafficking of RPW8.2-yellow
      fluorescent protein (YFP) to the EHM occurs transiently during early haustorial
      development and that lateral diffusion of RPW8.2-YFP within the EHM exceeds
      vesicle-mediated replenishment of RPW8.2-YFP in mature haustoria. Our findings
      imply the engagement of VAMP721/722 in a bifurcated trafficking pathway for pre
      invasive defense at the cell periphery and post-invasive defense at the EHM. 

PMID- 24941883
TI  - Knowledge, attitudes and practices concerning self-medication with antibiotics
      among university students in western China.
AB  - OBJECTIVES: To evaluate the knowledge, attitude and behaviours of university
      students on the use of antibiotics. METHODS: A knowledge-attitude-practice
      questionnaire was developed and distributed to undergraduate students of Xi'an
      Jiaotong University, comprising 18 schools/colleges in Shaanxi Province, western
      China. Chi-square test and logistic regression analysis were applied to identify
      risk factors associated with self-medication with antibiotics. RESULTS: Of the
      731 respondents (response rate = 73.1%), 294 (40.2%) had self-medicated with
      antibiotics in the past 6 months. Most of the antibiotics (59.2%) for self
      medication were purchased without prescription in retail pharmacies. The median
      score of students' knowledge about antibiotics was 4 (IQR: 3-6) of a maximum
      possible score of 10. Students had moderately accurate beliefs towards
      antibiotics. More than half of the students (56.5%) were storing antibiotics
      frequently. During self-medication, 16.7% of students claimed to have experienced
      adverse reactions, and 30.6% had used antibiotics to prevent common colds. The
      majority preferred to use broad-spectrum antibiotics, and nearly half preferred
      intravenous antibiotics. Over 44% of students had changed antibiotic dosage, and
      36.5% had switched to another antibiotic during the treatment course. Logistic
      regression analysis identified college and home town as independent risk factors
      for self-medication with antibiotics (P < 0.01). CONCLUSIONS: Undergraduate
      students had inadequate knowledge, moderately accurate beliefs and inappropriate
      practices concerning antibiotics, and a high rate of self-medication. This
      highlights the need for focused educational intervention and stricter
      governmental regulation concerning antibiotic use and sale in retail pharmacies.

PMID- 24941881
TI  - Development and evaluation of IgY ImmunoCapture PCR ELISA for detection of
      Staphylococcus aureus enterotoxin A devoid of protein A interference.
AB  - In the present study, a sensitive and specific IgY mediated ImmunoCapture-PCR
      ELISA (IC-PCR-ELISA) was developed for the detection of staphylococcal
      enterotoxin A (SEA) from culture supernatants and suspected contaminated samples.
      Due to the virtue of avian immunoglobulins (IgY) to have the least affinity
      towards staphylococcal protein A (SpA) responsible for false positives, we
      employed anti-SEA IgY for capture of SEA toxin and revealed with SEA specific
      rabbit antibodies conjugated to a 524bp DNA marker. Biotin-11-dUTP was
      incorporated during PCR amplification and post PCR analysis was performed by PCR
      ELISA. Unlike IgG immunocapture, IgY mediated immunocapture of SEA was free from
      false positives due to protein A. The developed assay was specific to SEA except
      for minor cross reactivity with staphylococcal enterotoxin E (SEE). Several raw
      milk samples were evaluated for the presence of SEA with and without enrichment.
      Three samples were found to be positive for SEA after enrichment for 8h. Though
      IC-PCR-ELISA for SEA showed 100% correlation with PCR analysis for sea gene, the
      assay was unique in terms of sensitivity of detecting ~10pg/ml of SEA toxin from
      spiked milk samples. Result of IC-PCR-ELISA was further confirmed by conventional
      methods of isolation and characterization. The presented method can be very
      useful for rapid analysis of milk samples for SEA contamination and can be
      further extended for detection of multiple SE's in different wells of same PCR
      plate using common DNA substrate. 

PMID- 24941885
TI  - Recent novel methods and approaches in sparsity-based compressive sensing and
      sparse learning have shown promising results. Introduction.

PMID- 24941880
TI  - Soy food and isoflavone intake and endometrial cancer risk: the Japan Public
      Health Center-based prospective study.
AB  - OBJECTIVE: Compared with western populations, the consumption of soy foods among
      Japanese is very high and the incidence of endometrial cancer very low. We
      evaluated the association of soy food and isoflavone intake with endometrial
      cancer risk in Japanese women. DESIGN: Prospective cohort study. SETTING: Ten
      public health centre areas in Japan. POPULATION: Forty nine thousand one hundred
      and twenty-one women of age 45-74 years who responded to a 5-year follow-up
      survey questionnaire. METHODS: Intakes of soy foods as well as other covariates
      were assessed in 1995-1998 by a self-administered food frequency questionnaire.
      Cox proportional hazards regression models were used to estimate hazard ratios
      (HR) and 95% confidence intervals (CI). MAIN OUTCOME MEASURE: Incidence of
      endometrial cancer. RESULTS: During an average of 12.1 years of follow up, 112
      newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes
      of soy food and isoflavone were not associated with the risk of endometrial
      cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy
      food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone
      intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). CONCLUSION: In this population
      based prospective cohort study of Japanese women, we observed no evidence of a
      protective association between soy food or isoflavone intake and endometrial
      cancer risk.

PMID- 24941886
TI  - Enhancing the Characterization of Epistemic Uncertainties in PM2.5 Risk Analyses.
AB  - The Environmental Benefits Mapping and Analysis Program (BenMAP) is a software
      tool developed by the U.S. Environmental Protection Agency (EPA) that is widely
      used inside and outside of EPA to produce quantitative estimates of public health
      risks from fine particulate matter (PM2.5 ). This article discusses the purpose
      and appropriate role of a risk analysis tool to support risk management
      deliberations, and evaluates the functions of BenMAP in this context. It
      highlights the importance in quantitative risk analyses of characterization of
      epistemic uncertainty, or outright lack of knowledge, about the true risk
      relationships being quantified. This article describes and quantitatively
      illustrates sensitivities of PM2.5 risk estimates to several key forms of
      epistemic uncertainty that pervade those calculations: the risk coefficient,
      shape of the risk function, and the relative toxicity of individual PM2.5
      constituents. It also summarizes findings from a review of U.S.-based
      epidemiological evidence regarding the PM2.5 risk coefficient for mortality from
      long-term exposure. That review shows that the set of risk coefficients embedded
      in BenMAP substantially understates the range in the literature. We conclude that
      BenMAP would more usefully fulfill its role as a risk analysis support tool if
      its functions were extended to better enable and prompt its users to characterize
      the epistemic uncertainties in their risk calculations. This requires expanded
      automatic sensitivity analysis functions and more recognition of the full range
      of uncertainty in risk coefficients. 

PMID- 24941887
TI  - Characterization of microsatellite markers developed from Prosopis rubriflora and
      Prosopis ruscifolia (Leguminosae - Mimosoideae), legume species that are used as
      models for genetic diversity studies in Chaquenian areas under anthropization in
      South America.
AB  - BACKGROUND: Prosopis rubriflora and Prosopis ruscifolia are important species in
      the Chaquenian regions of Brazil. Because of the restriction and frequency of
      their physiognomy, they are excellent models for conservation genetics studies.
      The use of microsatellite markers (Simple Sequence Repeats, SSRs) has become
      increasingly important in recent years and has proven to be a powerful tool for
      both ecological and molecular studies. FINDINGS: In this study, we present the
      development and characterization of 10 new markers for P. rubriflora and 13 new
      markers for P. ruscifolia. The genotyping was performed using 40 P. rubriflora
      samples and 48 P. ruscifolia samples from the Chaquenian remnants in Brazil. The
      polymorphism information content (PIC) of the P. rubriflora markers ranged from
      0.073 to 0.791, and no null alleles or deviation from Hardy-Weinberg equilibrium
      (HW) were detected. The PIC values for the P. ruscifolia markers ranged from
      0.289 to 0.883, but a departure from HW and null alleles were detected for
      certain loci; however, this departure may have resulted from anthropic
      activities, such as the presence of livestock, which is very common in the
      remnant areas. CONCLUSIONS: In this study, we describe novel SSR polymorphic
      markers that may be helpful in future genetic studies of P. rubriflora and P.
      ruscifolia.

PMID- 24941888
TI  - Comparative rangewide phylogeography of four endemic Taiwanese bat species.
AB  - Phylogeographic reconstructions of codistributed taxa can help reveal the
      interplay between abiotic factors, such as altitude and climate, and species
      specific attributes, in shaping patterns of population genetic structure. Recent
      studies also demonstrate the value of both rangewide sampling and species
      distribution modelling (SDM) in comparative phylogeography. Here, we combine
      these approaches to study the population histories of four phylogenetically
      related forest-dependent bat species. All are endemic to the mountainous island
      of Taiwan but show differences in their tolerance to altitude, with Murina
      gracilis considered to be a high-altitude specialist, M. recondita and Kerivoula
      sp. low-altitude specialists, and M. puta an altitudinal generalist. We tested
      the prediction that contrasting habitat preferences would impact on patterns of
      past and contemporary gene flow and found broad concordance between the results
      of population genetic analyses and species distribution models based on the Model
      for Interdisciplinary Research on Climate. Both lowland species showed evidence
      of genetic divergence between the east and west of the island, consistent with
      SDMs that indicated the Central Mountain Range (CMR) has presented a long-term
      and continuous barrier to gene flow since before the Last Glacial Maximum. In
      contrast, Murina gracilis and M. puta showed lower degrees of historical
      isolation and genetic differentiation associated with the CMR, reflecting greater
      gene flow, possibly coupled with past population growth in M. puta. Together our
      results highlight the usefulness of combining distribution models with
      phylogeographic analyses to understand the drivers of genetic structure. 

PMID- 24941889
TI  - Human pancreas endocrine cell populations and activating ABCC8 mutations.
AB  - BACKGROUND/AIMS: Activating mutations in the ABCC8 gene encoding the KATP channel
      subunit SUR1 cause beta-cell dysfunction with non-autoimmune diabetes mellitus in
      neonates or infants. We investigated whether activating ABCC8 mutations affect
      endocrine pancreas development. METHODS: We studied a male infant with compound
      heterozygous ABCC8 mutations (p.Arg826Trp/p.Ile93Thr) causing neonatal diabetes
      mellitus. He died of ketoacidosis. Postmortem pancreas specimens were evaluated
      by fluorescent microscopy after immunostaining for insulin, glucagon,
      somatostatin, and PCNA, and Hoechst 33342 nuclear staining. We compared the
      findings to those in 5 age-matched controls. RESULTS: The number of islets was
      decreased and the number of single or small clusters of insulin cells increased
      in the patient compared to the age-matched controls. The islets in the patient
      had an insulin-cell core surrounded by intermingled glucagon and somatostatin
      cells. The insulin/Hoechst surface ratio was decreased and the glucagon/Hoechst
      surface ratio increased in the patient (4.3 and 8.8%, respectively) versus the
      controls (8.2 and 3.1%, respectively). Somatostatin surface staining was similar
      in the patient and controls (4 vs. 4.7%). PCNA staining was increased 3- to 3.5
      fold, indicating increased insulin-cell proliferation compared to controls.
      CONCLUSION: Activating ABCC8 mutations impaired the balance between beta and
      alpha cells in the patient, suggesting an effect on beta-cell mass development.

PMID- 24941890
TI  - A meta-analysis of risk factors for depression in adults and children after
      natural disasters.
AB  - BACKGROUND: A number of studies have shown a range of negative psychological
      symptoms (e.g. depression) after exposure to natural disasters. The aim of this
      study was to determine risk factors for depression in both children and adults
      who have survived natural disasters. METHODS: Four electronic databases (PubMed,
      Embase, Web of Science, and PsychInfo) were used to search for observational
      studies (case-control, cross-sectional, and cohort studies) about depression
      following natural disasters. The literature search, study selection, and data
      extraction were conducted independently by two authors. Thirty-one articles were
      included in the study, of which twenty included adult participants and eleven
      included child participants. Summary estimates were obtained using random-effects
      models. Subgroup analysis, sensitivity analysis, and publication bias tests were
      performed on the data. RESULTS: The prevalence of depression after natural
      disasters ranged from 5.8% to 54.0% in adults and from 7.5% to 44.8% in children.
      We found a number of risk factors for depression after exposure to natural
      disasters. For adults, the significant predictors were being female ;not
      married;holding religious beliefs; having poor education; prior trauma;
      experiencing fear, injury, or bereavement during the disaster; or losing
      employment or property, suffering house damage as a result of the disaster. For
      children, the significant predictors were prior trauma; being trapped during the
      disaster; experiencing injury, fear, or bereavement during the disaster;
      witnessing injury/death during the disaster; or having poor social support.
      CONCLUSIONS: The current analysis provides evidence of risk factors for
      depression in survivors of natural disasters. Further research is necessary to
      design interventions to improve the mental health of survivors of natural
      disasters.

PMID- 24941893
TI  - Boerhaave syndrome resulting from homicidal blunt trauma.
AB  - Boerhaave syndrome is an uncommon condition with high rate of mortality that is
      higher than 90%. The syndrome has classically been associated with sudden severe
      chest pain after severe emesis or retching. However, traumatic esophageal rupture
      secondary to blunt injury has been occasionally reported in the literature,
      usually from unintentional injury. We report the first case of Boerhaave syndrome
      resulting from homicidally inflicted blunt trauma to the abdomen, which is a rare
      finding that can be easily missed during an autopsy. 

PMID- 24941892
TI  - Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel
      activators.
AB  - Cav1.2 and Cav1.3 are the main L-type Ca(2+) channel subtypes in the brain.
      Cav1.3 channels have recently been implicated in the pathogenesis of Parkinson's
      disease. Therefore, Cav1.3-selective blockers are developed as promising
      neuroprotective drugs. We studied the pharmacological properties of a pyrimidine
      2,4,6-trione derivative (1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6
      (1H,3H,5H)-trione, Cp8) recently reported as the first highly selective Cav1.3
      blocker. Here we show, in contrast to this previous study, that Cp8 reproducibly
      increases inward Ca(2+) currents of Cav1.3 and Cav1.2 channels expressed in tsA
      201 cells by slowing activation, inactivation and enhancement of tail currents.
      Similar effects are also observed for native Cav1.3 and Cav1.2 channels in mouse
      chromaffin cells, while non-L-type currents are unaffected. Evidence for a weak
      and non-selective inhibition of Cav1.3 and Cav1.2 currents is only observed in a
      minority of cells using Ba(2+) as charge carrier. Therefore, our data identify
      pyrimidine-2,4,6-triones as Ca(2+) channel activators. 

PMID- 24941894
TI  - Acute myeloid leukemia with myelodysplasia-related changes showing basophilic
      differentiation.

PMID- 24941896
TI  - The role of beta-blockers in septic patients.
AB  - beta-blockers are widely used to treat cardiovascular diseases and in the peri
      operative period in selected patients. The main benefit in terms of morbidity
      and/or mortality of their use is believed to be linked to specific effects on
      myocardial oxygen supply/demand balance, to anti-arrhythmic effects and anti
      inflammatory effects. Use of beta-blockers in severe sepsis is still under debate
      and if any, their appropriate indications remain unclear. In this article, we
      analyze the recent literature addressing the metabolic, immuno-modulatory and
      hemodynamic effects of non cardio-selective and of cardio-selective beta-blockers
      in experimental and human sepsis in order to help clarifying the potential place
      of these drugs in patients with severe sepsis. From this analysis, it appears
      that beta-adrenoceptor blocking agents may represent a therapeutic approach in
      patients with severe sepsis, in whom catecholaminergic hyperactivity including
      excessive tachycardia is supposed to play an aggravating role. However, many
      questions about effectiveness, safety and cardio-selectivity of the drugs and
      about the appropriate target population remain partially unanswered. Recently,
      esmolol, a short-time acting beta1-adrenoceptor blocker titrated to decrease
      heart rate below 95 beats/min was shown to exert beneficial effects in a
      monocentric randomized clinical trial including selected septic patients. Further
      large multicenter randomized trials are required to confirm the potential benefit
      of such a therapy in patients with severe sepsis. 

PMID- 24941895
TI  - A multiple antibiotic-resistant enterobacter cloacae strain isolated from a
      bioethanol fermentation facility.
AB  - An Enterobacter cloacae strain (E. cloacae F3S3) that was collected as part of a
      project to assess antibiotic resistance among bacteria isolated from bioethanol
      fermentation facilities demonstrated high levels of resistance to antibiotics
      added prophylactically to bioethanol fermentors. PCR assays revealed the presence
      of canonical genes encoding resistance to penicillin (ampC) and erythromycin
      (ermG). Assays measuring biofilm formation under antibiotic stress indicated that
      erythromycin induced biofilm formation in E. cloacae F3S3. Planktonic growth and
      biofilm formation were observed at a high ethanol content, indicating E. cloacae
      F3S3 can persist in a bioethanol fermentor under the highly variable
      environmental conditions found in fermentors. 

PMID- 24941897
TI  - Assessment of microperfusion in sepsis.
AB  - Microcirculatory alterations are frequent in sepsis and different mechanisms can
      be implied and variously studied. The severity of microvascular alterations is
      associated with organ dysfunction and mortality. The aim of this review is to
      make an overview of the most actual and used techniques applied on septic humans.
      We aimed at focus on the impact of different techniques on the evaluation of
      patients' management and outcome. 

PMID- 24941891
TI  - Caloric restriction and the aging process: a critique.
AB  - The main objective of this review is to provide an appraisal of the current
      status of the relationship between energy intake and the life span of animals.
      The concept that a reduction in food intake, or caloric restriction (CR), retards
      the aging process, delays the age-associated decline in physiological fitness,
      and extends the life span of organisms of diverse phylogenetic groups is one of
      the leading paradigms in gerontology. However, emerging evidence disputes some of
      the primary tenets of this conception. One disparity is that the CR-related
      increase in longevity is not universal and may not even be shared among different
      strains of the same species. A further misgiving is that the control animals, fed
      ad libitum (AL), become overweight and prone to early onset of diseases and
      death, and thus may not be the ideal control animals for studies concerned with
      comparisons of longevity. Reexamination of body weight and longevity data from a
      study involving over 60,000 mice and rats, conducted by a National Institute on
      Aging-sponsored project, suggests that CR-related increase in life span of
      specific genotypes is directly related to the gain in body weight under the AL
      feeding regimen. Additionally, CR in mammals and "dietary restriction" in
      organisms such as Drosophila are dissimilar phenomena, albeit they are often
      presented to be the very same. The latter involves a reduction in yeast rather
      than caloric intake, which is inconsistent with the notion of a common, conserved
      mechanism of CR action in different species. Although specific mechanisms by
      which CR affects longevity are not well understood, existing evidence supports
      the view that CR increases the life span of those particular genotypes that
      develop energy imbalance owing to AL feeding. In such groups, CR lowers body
      temperature, rate of metabolism, and oxidant production and retards the age
      related pro-oxidizing shift in the redox state. 

PMID- 24941898
TI  - Linear accelerator stereotactic radiosurgery in the management of intracranial
      arteriovenous malformations: long-term outcome.
AB  - BACKGROUND: Arteriovenous malformation (AVM) is one of the cerebrovascular
      diseases that bear a high risk of hemorrhage. The treatment modalities include
      microsurgical resection, endovascular embolization, stereotactic radiosurgery, or
      combinations that vary widely. Several large series have been reported, while
      data from Asian populations were few. The aim of this study was to examine the
      efficacy of linear accelerator stereotactic radiosurgery (LINAC SRS) for the
      treatment of intracranial AVMs, to evaluate the hemorrhage rate and to analyze
      associated factors. METHODS: One hundred and sixteen patients with AVM were
      treated with LINAC SRS in a single institute between September 1994 and May 2005
      and were retrospectively evaluated. The demographics of patients, clinical
      characteristics of AVM, the treatment modalities, and the parameters of the LINAC
      SRS were analyzed. Delayed toxicity and hemorrhage rate after treatment were also
      evaluated. The AVM obliteration and bleed rates were calculated using the Kaplan
      Meier method and Cox regression analyses. RESULTS: The efficacy rate with total
      obliteration after treatment was 81.9% (95 of 116 patients). The median interval
      to achieve total obliteration was 49 months. Microsurgical resection combined
      with SRS for residual AVMs achieved better obliteration rates compared to SRS
      alone (statistically significant, p = 0.001), while no significant difference was
      found between the embolization group and the group with no prior treatment (p =
      0.895). The Spetzler-Martin grade of AVM is a relative factor of obliteration,
      higher grades resulting in a worse outcome (p = 0.009). Obliteration was
      significantly influenced by AVM volume in univariate analysis (p = 0.034), and
      volume <5 cm(3) contributed to improved obliteration (p = 0.01). There was no
      statistically significant difference in the hemorrhagic rate and the complication
      rate between ruptured and unruptured AVMs, while the unruptured group had a
      higher obliteration rate (p = 0.024). The annual hemorrhage rate after LINAC SRS
      treatment was 1.9%. The bleeding rate was 3.3% in the first year after
      radiosurgery, 2.1% in the second year, 1.9% between the second and fifth year,
      and 1.5% between the fifth and tenth year. Patients with hemorrhagic events
      before radiosurgery appeared to have a higher rebleeding risk during the latency
      period. Twenty-three patients (19.8%) had late adverse effects with regard to
      posttreatment radiological follow-up, but only 1 (0.8%) had newly developed
      neurological deficits. CONCLUSION: LINAC SRS achieved a high obliteration rate
      and reduced the risk of hemorrhage effectively in ruptured and unruptured
      intracranial AVMs. Prior microsurgical resection provided better outcome, while
      embolization showed no benefit. Adverse effects after treatment are acceptable
      and require long-term follow-up.

PMID- 24941899
TI  - Survival of women with clear cell and papillary serous endometrial cancer after
      adjuvant radiotherapy.
AB  - BACKGROUND: Type II (papillary serous and clear cell) endometrial carcinoma (EC)
      is a rare subgroup and is considered to have an unfavorable prognosis. The
      purpose of this retrospective analysis was to elucidate the meaning of adjuvant
      radiotherapy (RT) for clinical outcome and to define prognostic factors in these
      patients (pts). METHODS: From 2004-2012 forty-two pts with type II EC underwent
      surgery followed by adjuvant RT at our department. Median age was 72 years. The
      majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4
      [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy
      (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy
      (IVB) boost. RESULTS: Five-year local recurrence free survival (LRFS), distant
      metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, and
      64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis
      (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was
      prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger
      pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed
      haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and
      DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor
      (p = .028). CONCLUSIONS: Adjuvant RT with EBRT/IVB ensures adequate local control
      in type II EC, but control rates remain lower than in type I EC. A benefit of
      additional adjuvant ChT could not be demonstrated and a general omission of EBRT
      cannot be recommended at this point. Lymphovascular infiltration and pT stage
      might be the best predictive factors for a benefit from combined local and
      systemic treatment.

PMID- 24941901
TI  - Emotional well-being of Vietnamese immigrant women during the transition to
      motherhood: A descriptive cohort study.
AB  - This study investigated the health and well-being of Vietnamese foreign brides
      recently immigrated to southern Taiwan. Forty-four participants were recruited
      during pregnancy and 23 were followed-up at six weeks post-partum. Standardized
      measures completed during face-to-face interviews revealed high levels of life
      stress, poor general health, low social support, and difficulty caring for their
      infant amongst participants. Estimated prevalence of probable antenatal
      depression was 32%, and 26% for probable post-partum depression using Edinburgh
      Postnatal Depression Scale (EPDS) scores of >= 13. Probable antenatal depression
      predicted postnatal depression. Pregnant immigrant women experienced a high level
      of difficult life circumstances and were significantly more likely to develop
      depressive symptoms after birth. Immigrant women with low social support during
      pregnancy were also more likely to report higher EPDS scores than well-supported
      women. Given these results, prevention and intervention activities are needed to
      promote maternal psychological well-being in disadvantaged women, especially
      immigrant brides.

PMID- 24941900
TI  - Histologic characterization of acellular dermal matrices in a porcine model of
      tissue expander breast reconstruction.
AB  - BACKGROUND: Acellular dermal matrices (ADMs) have been commonly used in expander
      based breast reconstruction to provide inferolateral prosthesis coverage.
      Although the clinical performance of these biologic scaffold materials varies
      depending on a number of factors, an in-depth systematic characterization of the
      host response is yet to be performed. The present study evaluates the biochemical
      composition and structure of two ADMs, AlloDerm((r)) Regenerative Tissue Matrix
      and AlloMaxTM Surgical Graft, and provides a comprehensive spatiotemporal
      characterization in a porcine model of tissue expander breast reconstruction.
      METHODS: Each ADM was characterized with regard to thickness, permeability, donor
      nucleic acid content, (residual double-stranded DNA [dsDNA]), and growth factors
      (basic fibroblast growth factor [bFGF], vascular endothelial growth factor
      [VEGF], and transforming growth factor-beta 1 [TGF-beta1]). Cytocompatibility was
      evaluated by in vitro cell culture on the ADMs. The host response was evaluated
      at 4 and 12 weeks at various locations within the ADMs using established metrics
      of the inflammatory and tissue remodeling response: cell infiltration,
      multinucleate giant cell formation, extent of ADM remodeling, and
      neovascularization. RESULTS: AlloMax incorporated more readily with surrounding
      host tissue as measured by earlier and greater cell infiltration, fewer foreign
      body giant cells, and faster remodeling of ADM. These findings correlated with
      the in vitro composition and cytocompatibility analysis, which showed AlloMax to
      more readily support in vitro cell growth. CONCLUSIONS: AlloMax and AlloDerm
      demonstrated distinct remodeling characteristics in a porcine model of tissue
      expander breast reconstruction.

PMID- 24941902
TI  - Do antidepressants make children and adolescents suicidal?

PMID- 24941903
TI  - New testing guidelines for hearing loss support next-generation sequencing:
      testing method may help determine genetic causes of hearing loss among patients
      whose phenotypes are not easily distinguished clinically.

PMID- 24941904
TI  - Mutations in NGLY1 gene linked with new genetic disorder: parents' reports of
      children's symptoms help facilitate the discovery.

PMID- 24941906
TI  - Are pharmacological interventions between conception and birth effective in
      improving reproductive outcomes in North American swine?
AB  - The objective of this review is to evaluate the effectiveness of using
      pharmacological compounds on reproductive outcomes, particularly litter size, in
      North American swine. While the opportunity to improve reproduction in North
      American pigs exists, numerous hurdles need to be overcome in order to achieve
      measureable results. In the swine industry, the majority of piglet losses are
      incurred during pregnancy and around farrowing. Over the last 20 years, a
      reduction in losses has been achieved through genetic selection and nutritional
      management; however, these topics are the focus of other reviews. This review
      will evaluate attempts to improve litter size by reducing losses at various
      stages of the reproductive process, from the time of conception to the time of
      farrowing, using pharmacological compounds. Generally, these compounds are used
      to either alter physiological processes related to fertilization, embryonic
      attachment or uterine capacity, etc., or to facilitate management aspects of the
      breeding females such as inducing parturition. Although some of the
      pharmacological agents reviewed here show some positive effects on improving
      reproductive parameters, the inconsistent results and associated risks usually
      outweigh the benefits gained. Thus, at the present time, the use of
      pharmacological agents to enhance reproduction in North American swine may only
      be recommended for herds with low fertility and presents an avenue of research
      that could be further explored.

PMID- 24941907
TI  - Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.
AB  - BACKGROUND: Prostaglandins have been used for induction of labour since the
      1960s. This is one of a series of reviews evaluating methods of induction of
      labour. This review focuses on prostaglandins given per vaginam, evaluating these
      in comparison with placebo (or expectant management) and with each other;
      prostaglandins (PGE2 and PGF2a); different formulations (gels, tablets,
      pessaries) and doses. OBJECTIVES: To determine the effects of vaginal
      prostaglandins E2 and F2a for third trimester cervical ripening or induction of
      labour in comparison with placebo/no treatment or other vaginal prostaglandins
      (except misoprostol). SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (1 March 2014) and bibliographies of relevant
      papers. SELECTION CRITERIA: Clinical trials comparing vaginal prostaglandins used
      for third trimester cervical ripening or labour induction with placebo/no
      treatment, with each other, or other methods listed above it on a predefined list
      of labour induction methods. DATA COLLECTION AND ANALYSIS: We assessed studies
      and extracted data independently. MAIN RESULTS: Seventy randomised controlled
      trials (RCTs) (11,487 women) are included. In this update seven new RCTs (778
      women) have been added. Two of these new trials compare PGE2 with no treatment,
      four compare different PGE2 formulations (gels versus tablets, or sustained
      release pessaries) and one trial compares PGF2a with placebo. The majority of
      trials were at unclear risk of bias for most domains.Overall, vaginal
      prostaglandin E2 compared with placebo or no treatment probably reduces the
      likelihood of vaginal delivery not being achieved within 24 hours. The risk of
      uterine hyperstimulation with fetal heart rate changes is increased (4.8% versus
      1.0%, risk ratio (RR) 3.16, 95% confidence interval (CI) 1.67 to 5.98, 15 trials,
      1359 women). The caesarean section rate is probably reduced by about 10% (13.5%
      versus 14.8%, RR 0.91, 95% CI 0.81 to 1.02, 36 trials, 6599 women). The overall
      effect on improving maternal and fetal outcomes (across a variety of measures) is
      uncertain.PGE2 tablets, gels and pessaries (including sustained release
      preparations) appear to be as effective as each other, small differences are
      detected between some outcomes, but these maybe due to chance. AUTHORS'
      CONCLUSIONS: Prostaglandins PGE2 probably increase the chance of vaginal delivery
      in 24 hours, they increase uterine hyperstimulation with fetal heart changes but
      do not effect or may reduce caesarean section rates. They increase the likelihood
      of cervical change, with no increase in operative delivery rates. PGE2 tablets,
      gels and pessaries appear to be as effective as each other, any differences
      between formulations are marginal but may be important.

PMID- 24941908
TI  - Searching for new meaning in PREVENT IV?: a project of ex-vivo vein graft
      engineering via transfection IV substudy.

PMID- 24941909
TI  - Grape seed proanthocyanidin extracts ameliorate podocyte injury by activating
      peroxisome proliferator-activated receptor-gamma coactivator 1alpha in low-dose
      streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats.
AB  - Podocytes are part of the glomerular filtration membrane in kidney and serve to
      prevent the filtration of protein from the blood. Several evidences suggest that
      mitochondrial dysfunction plays a critical role in the pathogenesis of diabetic
      nephropathy and it is an early event in podocyte injury. Mitochondrial
      dysfunction promotes oxidative stress that can favor the development of podocyte
      injury. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC
      1alpha) was considered to be a major regulator of metabolic homeostasis and
      mitochondrial function. Some studies indicated that polyphenols may improve
      mitochondrial dysfunction, maintain the podocyte integrity and have therapeutic
      effects on glomerular diseases by promoting PGC-1alpha expression. Our study
      investigated whether grape seed proanthocyanidin extracts (GSPE), a strong
      antioxidant, ameliorate podocyte injury by activating PGC-1alpha in low-dose
      streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats. After
      16 weeks of GSPE treatment, GSPE slightly increased the body weight and decreased
      plasma glucose, food intake, water intake and urine volume in diabetic rats.
      Further, GSPE significantly decreased 24 h albumin levels and increased the
      expression of nephrin and podocalyxin. The antioxidant levels were improved and
      the cellular damage of kidney in diabetic rats was also relieved effectively
      after the treatment. Moreover, GSPE increased the mRNA expression of
      mitochondrial biogenesis factors and mitochondrial DNA content. Finally, GSPE
      activated the expression of PGC-1alpha, silent mating type information regulation
      2 homolog 1 (SIRT1) and AMP-activated protein kinase (AMPK). These results
      suggest that GSPE ameliorate podocyte injury in diabetic nephropathy by the
      activation of AMPK-SIRT1-PGC-1alpha signalling, which appears to inhibit
      oxidative stress and mitochondrial dysfunction in the kidney. 

PMID- 24941910
TI  - Light-induced rapid Ca2+ response and MAPK phosphorylation in the cells
      heterologously expressing human OPN5.
AB  - Molecular imaging is a powerful tool for investigating intracellular signalling,
      but it is difficult to acquire conventional fluorescence imaging from
      photoreceptive cells. Here we demonstrated that human opsin5 (OPN5) photoreceptor
      mediates light-induced Ca(2+) response in human embryonic kidney (HEK293) and
      mouse neuroblastoma (Neuro2a) cell lines using a luminescence imaging system with
      a fluorescent indicator and a newly synthesized bioluminescent indicator. Weak
      light fluorescence and bioluminescence imaging revealed rapid and transient light
      stimulated Ca(2+) release from thapsigargin-sensitive Ca(2+) stores, whereas long
      lasting Ca(2+) elevation was observed using a conventional fluorescence imaging
      system. Bioluminescence imaging also demonstrated that OPN5 activation in HEK293
      cells induced a decrease in pertussis toxin-sensitive cAMP, confirming previous
      reports. In addition, ultraviolet radiation induced the phosphorylation of
      mitogen-activated protein kinases when OPN5 was stimulated in Neuro2a cells.
      These findings suggest that the combination of these imaging approaches may
      provide a new means to investigate the physiological characteristics of
      photoreceptors. 

PMID- 24941911
TI  - Workspace and pivot point for robot-assisted endoscope guidance in functional
      endonasal sinus surgery (FESS).
AB  - BACKGROUND: For the further development of robot-assisted endoscope guidance in
      functional endoscopic sinus surgery (FESS), ground data about the workspaces and
      endoscope movements in conventional FESS are needed. METHODS: Applying a self
      developed marker-based tracking system, we collected the pose data (position and
      orientation) of the endoscope and all other instruments used in five real sinus
      surgeries. RESULTS: The automated segmentation of the endoscope poses shows the
      shape of a hourglass, with a pivot region or pivot point at the 'waistline' of
      the hourglass, close to the nasal entrance in the nasal dome. CONCLUSION: We were
      able to identify a pivot point at the waistline of the segmented endoscope poses.
      The size of the pivot point corresponds with the diameter of the 4 mm endoscope.
      Because of the reduction to four degrees of freedom for endoscope motions (three
      rotations and one translation), easier and safer robot-assisted endoscope
      guidance becomes feasible.

PMID- 24941913
TI  - The curious influence of timing on the magical experience evoked by conjuring
      tricks involving false transfer: decay of amodal object permanence?
AB  - In magic tricks involving false transfer, the conjurer typically creates the
      illusion of transferring a coin from one hand into the other, which is then
      closed into a fist, while in reality the coin is kept hidden in the first hand.
      The magical experience occurs when the closed fist of the second hand is opened
      and shown to be empty. According to professional magicians, the magical
      experience evoked by this kind of tricks becomes noticeably weaker when the time
      interval between the false transfer and the opening of the fist increases. This
      observation is surprising, given that neither the length of this interval nor any
      obvious factors associated with it can be expected to change the spectators'
      intellectual conviction regarding the true location of the coin. We performed a
      controlled psychological experiment and obtained results corroborating these
      informal observations. Increasing the temporal interval from 1 to 32 s led to an
      average reduction of the strength of the magical experience of 38%. We discuss
      potential explanations of this curious phenomenon in terms of object persistence,
      object files and temporal amodal completion.

PMID- 24941914
TI  - The contribution of verbalization to action.
AB  - Previous studies have shown that verbalization, in the form of self-guided
      instruction, is an effective cognitive strategy used to enhance motor skill
      acquisition and performance. However, past research has not explicitly examined
      which aspects of motor output are affected (whether beneficially or
      deleteriously) by verbalization. In the current study, we conducted two separate
      experiments in which a total of 80 healthy participants, aged 18-27, completed a
      novel motor sequence learning task. Half of the participants in each experiment
      were pre-trained in the sequence using verbalization, while the other half was
      either trained motorically, or not trained at all. Rote memorization of verbal
      labels facilitated motor sequence learning, motor control, and action
      maintenance, but not action planning of the motor sequence. Potential underlying
      mechanisms as well as clinical implications are discussed. 

PMID- 24941912
TI  - Meiotic chromosome synapsis and recombination in Arabidopsis thaliana: new ways
      of integrating cytological and molecular approaches.
AB  - Meiosis is an evolutionary conserved mechanism that produces haploid gametes and
      is essential for the sexual reproduction of higher eukaryotes. Since the late
      nineteenth century, meiosis has been studied in plants due their large
      chromosomes compared with other organisms and due to advances in microscopy and
      cytological approaches. On the other hand, non-plant model organisms like budding
      yeast have been widely used recently in order to characterise the molecular and
      functional aspects of meiosis. Arabidopsis arose as a new meiotic model for
      plants during the last decade of the twentieth century. This emergence was
      sustained by different molecular and genetic advances, mainly by completing the
      full genome sequence in 2000. Since then, further development of molecular
      technologies and the cytological methodologies to analyse the meiotic dynamics in
      Arabidopsis have permitted researchers to establish plant meiosis at the
      forefront of international research. Some key plant meiotic recombination events
      have been established in Arabidopsis. These advances have placed researchers into
      the position to transfer their knowledge from this plant meiotic model to crops
      and are likely to have an impact on plant breeding and the development of
      agriculture in future years. 

PMID- 24941915
TI  - Provocative mechanical tests of the peripheral nervous system affect the joint
      torque-angle during passive knee motion.
AB  - This study aimed to determine the influence of the head, upper trunk, and foot
      position on the passive knee extension (PKE) torque-angle response. PKE tests
      were performed in 10 healthy subjects using an isokinetic dynamometer at 2
      degrees /s. Subjects lay in the supine position with their hips flexed to 90
      degrees . The knee angle, passive torque, surface electromyography (EMG) of the
      semitendinosus and quadriceps vastus medialis, and stretch discomfort were
      recorded in six body positions during PKE. The different maximal active positions
      of the cervical spine (neutral; flexion; extension), thoracic spine (neutral;
      flexion), and ankle (neutral; dorsiflexion) were passively combined for the
      tests. Visual analog scale scores and EMG were unaffected by body segment
      positioning. An effect of the ankle joint was verified on the peak torque and
      knee maximum angle when the ankle was in the dorsiflexion position (P < 0.05).
      Upper trunk positioning had an effect on the knee submaximal torque (P < 0.05),
      observed as an increase in the knee passive submaximal torque when the cervical
      and thoracic spines were flexed (P < 0.05). In conclusion, other apparently
      mechanical unrelated body segments influence torque-angle response since
      different positions of head, upper trunk, and foot induce dissimilar knee
      mechanical responses during passive extension. 

PMID- 24941916
TI  - The risk of acute coronary syndrome in rheumatoid arthritis in relation to tumour
      necrosis factor inhibitors and the risk in the general population: a national
      cohort study.
AB  - INTRODUCTION: The elevated risk of ischaemic heart disease in patients with
      rheumatoid arthritis (RA) has been linked to inflammation and disease severity.
      Treatment with tumour necrosis factor inhibitors (TNFis) is often effective in
      reducing disease activity and could possibly modify cardiovascular risk. Our
      objective in the study was to evaluate the risk of acute coronary syndrome (ACS)
      in patients with RA treated with TNFis compared with the risk among biologic
      naive RA patients and the general population. METHODS: By linkage of the Swedish
      National Patient Register and the Swedish Biologics Register, we identified a
      cohort of patients who were started on their first biologic, a TNFi, between 2001
      and 2010 (N = 7,704), and a cohort comprising matched biologic-naive RA patient
      referents at a 3:1 ratio. Furthermore, a matched comparator cohort (5:1 ratio)
      was extracted from the Swedish population register. The incidence rates of a
      first ACS event were calculated and compared between cohorts using Cox
      proportional hazards regression in three different risk windows: 'ever-exposed',
      'actively on TNFi' and 'short-term exposure' (active treatment maximized to 2
      years). The models were adjusted for disease duration, joint surgery, comorbidity
      and socioeconomic factors, and, in a sensitivity analysis including a
      subpopulation started on therapy beginning 1 January 2006 or later, for dispensed
      drugs. RESULTS: Based on 221 events in 7,704 patients (comprising 32,621 person
      years) treated with TNFi biologics, the hazard ratio ((HR); ever-exposed) for ACS
      among the TNFi-exposed RA patients compared with biologic-naive RA patients was
      0.8 (95% confidence interval (CI) = 0.7 to 0.95). In comparison with the general
      population referents, statistical analysis using fully adjusted models resulted
      in a HR of 2.0 (95% CI = 1.8 to 2.3) for biologic-naive RA patients and a HR of
      1.6 (95% CI = 1.4 to 1.9) for the TNFi-exposed group. Similar risk estimates were
      obtained using the other two risk windows. A sensitivity analysis in which we
      compared the TNFi-exposed patients included from 1 January 2006 onward with
      biologic-naive patients resulted in a HR (ever-exposed) of 0.7 (95% CI = 0.5 to
      1.0). CONCLUSIONS: RA patients treated with TNFi had a lower risk of ACS compared
      with biologic-naive RA patients. Compared with the general population, the risk
      among patients with RA was elevated, although the difference was less pronounced
      among the TNFi-exposed patients. This finding could be attributable to the TNFi
      as such, or it could correspond to a lower degree of inflammation in the TNFi
      treated group.

PMID- 24941918
TI  - Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized
      by different immunoglobulin E-binding properties.
AB  - BACKGROUND: Pomegranate allergy is associated with sensitization to non-specific
      lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the
      non-specific nsLTPs expressed in pomegranate at the molecular level and to study
      their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross
      reactivity with peach nsLTP (Pru p 3). METHODS: A non-equilibrium two-dimensional
      (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate
      PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested
      by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera
      from pomegranate-allergic patients. For final identification, pomegranate nsLTPs
      were purified by chromatography and subjected to trypsin digestion and mass
      spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA
      cloning of three pomegranate nsLTPs were integrated in the database that was
      subsequently searched for MS data interpretation. RESULTS: Four nsLTPs were
      identified by 2-D immunoblotting. The detected proteins showed different IgE
      binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS
      analyses led to the identification of three nsLTP isoforms with 66-68% amino acid
      sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. CONCLUSIONS:
      By 2-D electrophoresis, we could separate different nsLTP isoforms possessing
      different IgE-binding properties, which might reflect peculiar allergenic
      potencies. The contribution of Pru p 3 to prime sensitization is not central as
      in other plant nsLTPs.

PMID- 24941917
TI  - Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and
      CASP8AP2 contribute to the structural coverage of the Human Cancer Protein
      Interaction Network.
AB  - High-quality solution NMR structures of three homeodomains from human proteins
      ALX4, ZHX1 and CASP8AP2 were solved. These domains were chosen as targets of a
      biomedical theme project pursued by the Northeast Structural Genomics Consortium.
      This project focuses on increasing the structural coverage of human proteins
      associated with cancer. 

PMID- 24941919
TI  - One-step refolding and purification of recombinant human tumor necrosis factor
      alpha (rhTNF-alpha) using ion-exchange chromatography.
AB  - Protein refolding is a key step for the production of recombinant proteins,
      especially at large scales, and usually their yields are very low.
      Chromatographic-based protein refolding techniques have proven to be superior to
      conventional dilution refolding methods. High refolding yield can be achieved
      using these methods compared with dilution refolding of proteins. In this work,
      recombinant human tumor necrosis factor-alpha (rhTNF-alpha) from inclusion bodies
      expressed in Escherichia coli was renatured with simultaneous purification by ion
      exchange chromatography with a DEAE Sepharose FF column. Several chromatographic
      parameters influencing the refolding yield of the denatured/reduced rhTNF-alpha,
      such as the urea concentration, pH value and concentration ratio of
      glutathione/oxidized glutathione in the mobile phase, were investigated in
      detail. Under optimal conditions, rhTNF-alpha can be renatured and purified
      simultaneously within 30 min by one step. Specific bioactivity of 2.18 * 10(8)
      IU/mg, purity of 95.2% and mass recovery of 76.8% of refolded rhTNF-alpha were
      achieved. Compared with the usual dilution method, the ion exchange
      chromatography method developed here is simple and more effective for rhTNF-alpha
      refolding in terms of specific bioactivity and mass recovery.

PMID- 24941920
TI  - All-printed flexible organic transistors enabled by surface tension-guided blade
      coating.
AB  - A combination of surface energy-guided blade coating and inkjet printing is used
      to fabricate an all-printed high performance, high yield, and low variability
      organic thin film transistor (OTFT) array on a plastic substrate. Functional inks
      and printing processes were optimized to yield self-assembled homogenous thin
      films in every layer of the OTFT stack. Specifically, we investigated the effect
      of capillary number, semiconductor ink composition (small molecule-polymer
      ratio), and additive high boiling point solvent concentrations on film fidelity,
      pattern design, device performance and yields. 

PMID- 24941922
TI  - Heavy menstrual bleeding and quality of life.

PMID- 24941921
TI  - Fatigue in children with juvenile idiopathic arthritis: reliability of the
      "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale".
AB  - The aim of the study was (1) to translate the "Pediatric Quality of Life
      Inventory-Multidimensional Fatigue Scale" (PedsQL-Fatigue) into Brazilian
      Portuguese language and culture and evaluate its reliability and (2) to measure
      fatigue among patients with juvenile idiopathic arthritis (JIA): (1) Translation
      of the PedsQL-Fatigue by two bilingual researchers; (2) Backtranslation into
      English assessed by the authors of the original version; (3) Pilot study with
      five patients followed in the Pediatric Rheumatology Outpatient Clinic and their
      parents; and (4) Field study and assessment of measurement properties (internal
      consistency, reproducibility, and construct validity). In this stage, the scale
      was administered to 67 patients with JIA and 63 healthy individuals, aged from 2
      to 18 years old, matched by age (from 2 to 4, 5 to 7, 8 to 12, and from 13 to 18
      years old). Cronbach's alpha coefficient ranged from 0.6 to 0.8 for children and
      parents, indicating the instrument's good internal consistency. The scale's
      construct validity was confirmed by a satisfactory Spearman's coefficient between
      the PedsQL-Fatigue and the generic PedsQL 4.0 (0.840 for the children and 0.742
      for the parents). Reproducibility was also adequate (0.764 for the children and
      0.938 for the parents). No differences were found between the scores obtained by
      the JIA group and control group, though lower scores were observed among patients
      with clinically active JIA when compared to those without clinical activity. The
      PedsQL-Fatigue is a valid and reliable tool, and that can be used to measure
      fatigue among patients with JIA.

PMID- 24941923
TI  - Self-efficacy moderates but collective efficacy mediates between motivational
      climate and athletes' well-being.
AB  - BACKGROUND: The relationship between perceived motivational climate and athletes'
      well-being may depend on personal resource factors such as self-efficacy beliefs
      which are expected to shield individuals from negative outcomes when
      environmental factors may not suffice to secure positive outcomes. We explored
      the roles of self-efficacy and collective efficacy by investigating whether they
      operated either as moderators or as mediators within this relationship. METHODS:
      Study 1 was carried out among 56 athletes (basketball, volleyball, or soccer
      players), with a two-week follow-up, whereas Study 2 was conducted among 113
      soccer players, with three measurement points (baseline, two-month follow-up, and
      nine-month follow-up). Their satisfaction with sport skills and performance
      served as an index of well-being. RESULTS: The findings of Study 1 indicated that
      general self-efficacy moderated the relationship between task-oriented
      motivational climate and satisfaction. Task-oriented climate predicted
      satisfaction only among athletes with low self-efficacy. Study 2 showed that self
      efficacy moderated the link between task-oriented motivational climate and
      satisfaction at nine-month follow-up. In contrast, collective efficacy at two
      month follow-up mediated the relationship between perceived motivational climate
      at baseline and satisfaction at nine-month follow-up. CONCLUSIONS: Athletes are
      at risk for lower well-being if they perceive a negative task-involving climate
      and if they harbor either low general self-efficacy or low personal-barrier self
      efficacy.

PMID- 24941925
TI  - Postsynthetic modification of an amino-tagged MOF using peptide coupling
      reagents: a comparative study.
AB  - The suitability of four peptide coupling reagents for postsynthetic modification
      (PSM) of amino-tagged metal-organic frameworks (MOFs) with carboxylic acids was
      investigated. Mild reaction conditions at room temperature allow effective
      covalent attachment of drugs and biomolecules inside the pores of MOFs with
      moderate chemical stability. 

PMID- 24941924
TI  - Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations,
      BH4 responsiveness and evidence of a founder effect.
AB  - The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is
      unknown, although it has been suggested that PKU variants could have a
      differential geographical distribution. Genotype-phenotype correlations and
      genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have
      never been performed. We sequenced the PAH gene and determined the geographic
      origin of each allele, mini-haplotype associated, genotype-phenotype correlations
      and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The
      mutational spectrum included 34 variants with c.60+5G>T being the most frequent
      (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or
      genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype
      phenotype correlation was concordant in 70.8%. The genotype-based prediction to
      BH4 -responsiveness was 41.7%, this information could be useful for the rational
      selection of candidates for BH4 testing and therapy. 

PMID- 24941926
TI  - Recent declines in induction of labor by gestational age.
AB  - After nearly 20 years of consecutive increases, induction of labor for singleton
      births reached a high of 23.8% in 2010, then declined in 2011 (23.7%) and 2012
      (23.3%). Trends in induction rates vary by gestational age, with rates for most
      gestational age groups declining since 2010. Induction rates for births at 36,
      37, and 38 weeks have declined since 2006, with the largest decrease at 38 weeks.
      From 2006 through 2012, induction rates at 38 weeks of gestation declined for all
      maternal age groups under 40 and for each of the largest race and Hispanic origin
      groups. Induction rates at 38 weeks declined for 36 states and the District of
      Columbia (DC) from 2006 through 2012, with declines ranging from 5% to 48%; rates
      for 31 states and DC declined at least 10%. During the 1980s, 1990s, and through
      2006, the length of pregnancies in the United States shortened (1). From 1981
      through 2006, the proportion of infants born at less than 39 completed weeks of
      gestation increased nearly 60%, while births at 39 weeks or more declined more
      than 20%. This shift in the gestational age distribution has been associated with
      greater use of cesarean delivery and induction of labor prior to full term (2-4).
      In more recent years, however, the trend towards shorter gestational ages has
      partially reversed. Since 2006, births delivered at less than 39 weeks have
      declined (down 12%), and births at 39 weeks or more have increased (up 9%) (1).
      This report explores trends in induction of labor for singleton births by
      gestational age, maternal age, race and Hispanic origin, and state for 2006-2012.

PMID- 24941927
TI  - Concurrent use of methotrexate and celecoxib increases risk of silent liver
      fibrosis in rheumatoid arthritis patients with subclinical reduced kidney
      function.
AB  - We evaluated the effects of concurrent use of methotrexate and celecoxib on
      silent liver and kidney damages in rheumatoid arthritis (RA) patients. We
      enrolled 92 RA patients with normal laboratory results related to liver and
      kidney functions, who had received methotrexate and celecoxib concurrently over 6
      months. Liver stiffness measurement (LSM) using transient elastography and
      ultrasonography were performed along with blood and urine tests. Estimated
      glomerular filtration rate (eGFR) was calculated by both the Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in
      Renal Disease (MDRD) equations. Initial eGFR represented kidney function at the
      time of the initiation of celecoxib. The cutoff for abnormal LSM values was
      adopted as 5.3 kPa. The optimal cutoff of each eGFR for abnormal LSM values was
      also calculated. The median age of patients was 55 years old (74 women). The
      median LSM was 4.4 kPa and the median eGFRs and median initial eGFRs ranged from
      89 to 99 mL/min/1.73 m(2). The cumulative doses of methotrexate and celecoxib and
      their concurrent administration duration did not affect LSM values and eGFRs.
      Both eGFRs were significantly associated with LSM values. Patients with initial
      eGFR(CKD-EPI), initial eGFR(MDRD), and eGFR(CKD-EPI) below each optimal cutoff
      had significantly high risks for silent liver fibrosis (RR 9.4, 10.3, and 4.4, p
      < 0.001, respectively). Both initial eGFRs (CKD-EPI and MDRD) and eGFR (CKD-EPI)
      were significant predictors for the development of silent liver fibrosis in RA
      patients who had received methotrexate and celecoxib concurrently for at least 6
      months.

PMID- 24941928
TI  - "A gift from heaven" or "This was not for me". A mixed methods approach to
      describe experiences of participation in an outsourced physical activity program
      for persons with rheumatoid arthritis.
AB  - Most persons with rheumatoid arthritis (RA) do not perform health-enhancing
      physical activity (HEPA). Evaluations of innovative HEPA programs need to be
      complemented with descriptive and qualitative data from the users. The aim of
      this mixed methods study was to explore and describe how a subgroup of the RA
      population perceives participation during the first year of an outsourced 2-year
      HEPA program. Data were collected by a study-specific postal survey to 220
      program participants (response rate 87%, n = 191) and by interviews with a
      purposefully selected subsample of 35, including completers and dropouts. The
      survey data were analyzed by descriptive statistics and the interviews by
      qualitative content analysis.The survey demonstrated increased self-reported
      physical activity in 165 participants (86%). After the first year of the program,
      participants reported having performed "regular" or "periodical" circuit training
      (78%) and physical activity in daily life (92%). The most valued program
      components were circuit training and physical activity in daily life, both rated
      median 5/5. Coach support, prompts by text messages, and expert lectures were
      rated median 4/5. Five categories emerged from the interviews describing
      expectations, facilitators, gains, maintenance, and obstacles/suggestions for
      improvement of the program. The results demonstrate that HEPA outside health care
      is highly appreciated by a subgroup of the RA population. Professional coaching
      and prompts by text messages seem to be particularly useful facilitators.
      Individual preferences emphasize the need to tailor settings, exercise formats,
      and behavioral support for HEPA even in a narrow, self-selected group with RA.

PMID- 24941929
TI  - Unanswered questions in the management of axial spondyloarthritis: an opinion
      piece.

PMID- 24941930
TI  - Discriminating infectious meningitis versus neuropsychiatric involvement in
      patients with systemic lupus erythematosus: a single-center experience.
AB  - The objective of this study is to identify the clinical differences between
      infectious meningitis and neuropsychiatric systemic lupus erythematosus (NPSLE)
      in patients with SLE. Clinical manifestations, laboratory test results, and
      prognoses of 14 SLE patients complicated with various infectious meningitis,
      hospitalized in the Affiliated Drum Tower Hospital of Nanjing University Medical
      School in the past 7 years, were reviewed and compared with those of 34
      concomitantly treated NPSLE patients. Our study shows that mortality rate was
      much higher in SLE patients with infectious meningitis than in NPSLE patients.
      Compared to NPSLE, those with infectious meningitis had lower SLE Disease
      Activity Index (SLEDAI), but higher doses of corticosteroids 1 month before the
      occurrence of CNS symptoms. Headache, high fever, and vomiting were more common
      in patients with infectious meningitis, accompanied with the elevation of C
      reactive protein level. Cerebrospinal fluid (CSF) examination showed increased
      levels of leukocytes and proteins but decreased glucose level in patients with
      infectious meningitis. We conclude that for SLE patients exhibiting CNS symptoms,
      high fever, high intake of corticosteroids, and abnormal CSF are important clues
      for the coexistence of infectious meningitis, especially tuberculous meningitis.

PMID- 24941931
TI  - Evaluation of the spectra Optia(r) mononuclear cell collection procedure in
      multiple myeloma patients.
AB  - BACKGROUND: Peripheral blood stem cell (PBSC) rescue following myeloablative
      therapy is a mainstay of cancer therapy. To evaluate the ability of the Spectra
      Optia Apheresis System (SO), a newly developed apheresis device, the device was
      studied in multiple myeloma patients undergoing a first autologous PBSC
      transplant. AIM: To demonstrate that neutrophil recovery was not inferior to
      historical controls when SO harvested PBSCs were reinfused following
      myeloablative therapy. METHODS: Multiple myeloma patients were mobilized
      according to the standard practice at four clinical sites. Following
      mobilization, MNC collections were performed on the SO. The collected cells were
      cryopreserved and reinfused following myeloablative chemotherapy. Neutrophil
      recovery defined by an absolute neutrophil count exceeding 500/MUL (ANC500) was
      compared to historical data for patients transplanted following apheresis using
      the COBE Spectra (CS) device. RESULTS: The median day to neutrophil recovery was
      12 days (range 10-14 days), with no significant difference in engraftment
      comparing patients transplanted with stem cells collected using the SO versus
      historical cohort of patients collected with the CS. CD34+ cell and MNC
      collection efficiency (CE) were 69.3% and 65.0% for the SO and CS, respectively.
      Platelet CE, product hematocrit and product granulocytes (as % of WBCs) using the
      SO were 21%, 2.3% and 28%, respectively. There were no device-related severe
      adverse events. CONCLUSIONS: The study's results confirm that the Spectra Optia
      Apheresis System's MNC Collection Protocol is safe and effective for its intended
      use and that engraftment kinetics of cells collected by SO is not inferior to the
      CS System.

PMID- 24941932
TI  - [Focal therapy for prostate cancer in Germany - 2014 status].
AB  - BACKGROUND: In localized low-risk prostate cancer (PCa), there is a therapeutic
      dilemma between possible overtreatment by one of the standard therapies and
      potentially insufficient cancer control by active surveillance (AS). Focal
      therapy (FT) provides an alternative therapeutic option as it aims to preserve
      the organ and to eliminate the cancer focus at the same time. METHODS: In this
      article the current state of FT for localized low-risk prostate carcinoma in
      Germany is described. In addition, criteria that should be used to select
      patients for FT are proposed. RESULTS: Currently, the effectiveness of FT is
      under evaluation by two multicenter, prospective studies in Germany: TOOKAD and
      HEMI. However, localized low-risk prostate carcinoma remains a diagnostic
      challenge: Multiparametric MRI as well as histopathological second opinion are
      considered mandatory in addition to transrectal biospy. CONCLUSION: The
      oncological outcome of both the TOOKAD and HEMI study will be crucial for any
      form of FT for prostate carcinoma in Germany in the future. However, there is a
      remarkably high acceptance of FT among patients.

PMID- 24941933
TI  - [Smartphone applications for urological training].

PMID- 24941934
TI  - Pharmacokinetics of ceftriaxone in plasma and bone of patients undergoing hip or
      knee surgery.
AB  - OBJECTIVES: Patients undergoing hip or knee replacement therapy are routinely
      pretreated with antibiotics before surgery. It is controversial in which
      antibiotic is the treatment of choice for this purpose. One possibility is the
      cephalosporin ceftriaxone. Here, we wanted to know if effective tissue
      concentrations are reached. METHODS: We studied plasma and bone kinetics of
      ceftriaxone in orthopaedic patients (n = 22) treated with ceftriaxone (2 g)
      immediately prior operation. Plasma samples were withdrawn before and at three
      time points after ceftriaxone infusion. After bone replacement, extracts from
      cancellous bone or cortical bone were obtained, and ceftriaxone was quantified
      using column chromatography. KEY FINDINGS: The plasma kinetics of ceftriaxone and
      distribution into bone were analysed using a population approach (ADAPT 5). The
      population mean of the area under the curve (AUC) was 140 mg h/l. A cancellous
      bone to plasma concentration ratio of 1.12 +/- 1.29 was achieved 5 h after start
      of infusion. The half-life of uptake into the cortical bone was less (8.4 h) than
      into cancellous bone (12.1 h, P < 0.05). CONCLUSIONS: Under these experimental
      conditions, concentrations of ceftriaxone in cancellous and cortical bone should
      be adequate to protect the patients against usual ceftriaxone-sensitive
      nosocomial infections and are substantially lower than the plasma concentrations.

PMID- 24941935
TI  - 46,XY disorder of sex development in a sudanese patient caused by a novel
      mutation in the HSD17B3 gene.
AB  - In this study, we present a Sudanese 46,XY patient raised as a female and
      diagnosed at the age of 20 years with having 17beta-hydroxysteroid dehydrogenase
      type 3 (17beta-HSD3) deficiency. She presented with primary amenorrhea,
      undeveloped breasts and a male pattern of secondary sexual characteristics.
      Examination of her external genitalia showed type IV genital circumcision.
      Steroid measurements both in urine and serum pointed to 17beta-HSD3 deficiency. A
      novel homozygous splice-site mutation [c.524 + 2T>A] was detected in intron 7 of
      the HSD17B3 gene. In this patient, steroid concentration clearly supported both
      the clinical diagnosis of 17beta-HSD3 deficiency and the functional relevance of
      the mutation. Interestingly, despite of the type IV genital circumcision, the
      patient expressed her interest in reassigning her sex from female to male.

PMID- 24941936
TI  - CT versus FDG-PET/CT response evaluation in patients with metastatic colorectal
      cancer treated with irinotecan and cetuximab.
AB  - We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy
      glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in
      patients with metastatic colorectal cancer and correlated the findings with
      survival and KRAS status. From 2006 to 2009, patients were included in a phase II
      trial and treated with cetuximab and irinotecan every second week. They underwent
      FDG-PET/CT examination at baseline and after every fourth treatment cycle.
      Response evaluation was performed prospectively according to Response Evaluation
      Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron
      Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall
      responses were registered. Sixty-one patients were eligible for response
      evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and
      progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%,
      stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate
      11%. Response agreement was poor, kappa-coefficient 0.19. Hazard ratio for
      overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher
      for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none
      had PR but 44% had PMR. In conclusion, morphologic and metabolic response
      agreement was poor primarily because a large part of the patients shifted from SD
      with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger
      fraction of the patients with KRAS mutations had a metabolic treatment response. 

PMID- 24941937
TI  - Efficacy of ethylene-diamine-tetra-acetic acid associated with chlorhexidine on
      intracanal medication removal: a scanning electron microscopy study.
AB  - The aim of this study was to evaluate the effectiveness of 17% ethylene-diamine
      tetra-acetic acid (EDTA) used alone or associated with 2% chlorhexidine gel (CHX)
      on intracanal medications (ICM) removal. Sixty single-rooted human teeth with
      fully formed apex were selected. The cervical and middle thirds of each canal
      were prepared with Gates Glidden drills and rotary files. The apical third was
      shaped with hand files. The specimens were randomly divided into two groups
      depending on the ICM used after instrumentation: calcium hydroxide Ca(OH)(2) +CHX
      or Ca(OH)(2) +sterile saline (SS). After seven days, each group was divided into
      subgroups according to the protocol used for ICM removal: instrumentation and
      irrigation either with EDTA, CHX+EDTA, or SS (control groups). All specimens were
      sectioned and processed for observation of the apical thirds by using scanning
      electron microscopy. Two calibrated evaluators attributed scores to each
      specimen. The differences between the protocols for ICM removal were analyzed
      with Kruskal-Wallis and Mann-Whitney U tests. Friedman and Wilcoxon signed rank
      tests were used for comparison between the score of debris obtained in each root
      canal third. Remains of Ca(OH)(2) were found in all specimens independently of
      the protocol and ICM used (P > 0.05). Seventeen percent EDTA showed the best
      results in removing ICM when used alone (P < 0.05), particularly in those
      associated with CHX. It was concluded that the chelating agent 17% EDTA
      significantly improved the removal of ICM when used alone. Furthermore, the type
      of the vehicle associated with Ca(OH)(2) also plays a role in the ICM removal.

PMID- 24941939
TI  - Author's reply to Madhok.

PMID- 24941938
TI  - Deconstructing the effect of self-directed study on episodic memory.
AB  - Self-directed learning is often associated with better long-term memory
      retention; however, the mechanisms that underlie this advantage remain poorly
      understood. This series of experiments was designed to "deconstruct" the notion
      of self-directed learning, in order to better identify the factors most
      responsible for these improvements to memory. In particular, we isolated the
      memory advantage that comes from controlling the content of study episodes from
      the advantage that comes from controlling the timing of those episodes. Across
      four experiments, self-directed learning significantly enhanced recognition
      memory, relative to passive observation. However, the advantage for self-directed
      learning was found to be present even under extremely minimal conditions of
      volitional control (simply pressing a button when a participant was ready to
      advance to the next item). Our results suggest that improvements to memory
      following self-directed encoding may be related to the ability to coordinate
      stimulus presentation with the learner's current preparatory or attentional
      state, and they highlight the need to consider the range of cognitive control
      processes involved in and influenced by self-directed study.

PMID- 24941940
TI  - Marriage, like income and education, fails to provide shelter for women against
      HIV infection in sub-Saharan Africa: widowhood and divorce increase the risk.
AB  - Since HIV infection and its consequence, AIDS, were first described, many initial
      assumptions have proven to be wrong. In Africa, it is women who bear the greater
      burden of the disease. In many ways they are less visible than men, although at
      least as much at risk, often even more so. Marriage is no protection against
      infection, and widowhood and divorce leave them still more vulnerable. This is
      reflected in higher proportions of infection for bereaved and separated wives.
      Programmes of control, which depend on education, testing and access to treatment
      should be visible and accessible to all women in sub-Saharan Africa.

PMID- 24941941
TI  - Affect Consciousness in children with internalizing problems: Assessment of
      affect integration.
AB  - Affect integration was operationalized through the Affect Consciousness (AC)
      construct as degrees of awareness, tolerance, nonverbal expression and conceptual
      expression of 11 affects. These aspects are assessed through a semi-structured
      Affect Consciousness Interview (ACI) and separate rating scales (Affect
      Consciousness Scales (ACSs)) developed for use in research and clinical work with
      adults with psychopathological disorders. Age-adjusted changes were made in the
      interview and rating system. This study explored the applicability of the
      adjusted ACI to a sample of 11-year-old children with internalizing problems
      through examining inter-rater reliability of the adjusted ACI, along with
      relationships between the AC aspects and aspects of mental health as symptoms of
      depression, symptoms of anxiety, social competence, besides general intelligence.
      Satisfactory inter-rater reliability was found, as well as consistent
      relationships between the AC aspects and the various aspects of mental health, a
      finding which coincides with previous research. The finding indicates that the
      attainment of the capacity to deal adaptively with affect is probably an
      important contributor to the development of adequate social competence and maybe
      in the prevention of psychopathology in children. The results indicate that the
      adjusted ACI and rating scales are useful tools in treatment planning with
      children at least from the age of 11 years. 

PMID- 24941942
TI  - Torsion of a lipoma of parietal peritoneum: a rare case mimicking acute
      appendicitis.
AB  - Lipomas are found most often on the torso, neck, upper thighs, upper arms and
      armpits; they can also occur almost anywhere in the body. Parietal peritoneum
      lipoma is a rare intraoperative finding during abdominal surgery. We present a
      case of a torted, pedunculated parietal wall lipoma in the right iliac fossa that
      gave rise to a clinical diagnosis of appendicitis. So far only one case has been
      reported. 

PMID- 24941943
TI  - Thrombospondin-4 controls matrix assembly during development and repair of
      myotendinous junctions.
AB  - Tendons are extracellular matrix (ECM)-rich structures that mediate muscle
      attachments with the skeleton, but surprisingly little is known about molecular
      mechanisms of attachment. Individual myofibers and tenocytes in Drosophila
      interact through integrin (Itg) ligands such as Thrombospondin (Tsp), while
      vertebrate muscles attach to complex ECM fibrils embedded with tenocytes. We show
      for the first time that a vertebrate thrombospondin, Tsp4b, is essential for
      muscle attachment and ECM assembly at myotendinous junctions (MTJs). Tsp4b
      depletion in zebrafish causes muscle detachment upon contraction due to defects
      in laminin localization and reduced Itg signaling at MTJs. Mutation of its
      oligomerization domain renders Tsp4b unable to rescue these defects,
      demonstrating that pentamerization is required for ECM assembly. Furthermore,
      injected human TSP4 localizes to zebrafish MTJs and rescues muscle detachment and
      ECM assembly in Tsp4b-deficient embryos. Thus Tsp4 functions as an ECM scaffold
      at MTJs, with potential therapeutic uses in tendon strengthening and repair. 

PMID- 24941944
TI  - Differential chemosensitivity to antifolate drugs between RAS and BRAF melanoma
      cells.
AB  - BACKGROUND: The importance of the genetic background of cancer cells for the
      individual susceptibility to cancer treatments is increasingly apparent. In
      melanoma, the existence of a BRAF mutation is a main predictor for successful
      BRAF-targeted therapy. However, despite initial successes with these therapies,
      patients relapse within a year and have to move on to other therapies. Moreover,
      patients harbouring a wild type BRAF gene (including 25% with NRAS mutations)
      still require alternative treatment such as chemotherapy. Multiple genetic
      parameters have been associated with response to chemotherapy, but despite their
      high frequency in melanoma nothing is known about the impact of BRAF or NRAS
      mutations on the response to chemotherapeutic agents. METHODS: Using cell
      proliferation and DNA methylation assays, FACS analysis and quantitative-RT-PCR
      we have characterised the response of a panel of NRAS and BRAF mutant melanoma
      cell lines to various chemotherapy drugs, amongst them dacarbazine (DTIC) and
      temozolomide (TMZ) and DNA synthesis inhibitors. RESULTS: Although both, DTIC and
      TMZ act as alkylating agents through the same intermediate, NRAS and BRAF mutant
      cells responded differentially only to DTIC. Further analysis revealed that the
      growth-inhibitory effects mediated by DTIC were rather due to interference with
      nucleotide salvaging, and that NRAS mutant melanoma cells exhibit higher activity
      of the nucleotide synthesis enzymes IMPDH and TK1. Importantly, the enhanced
      ability of RAS mutant cells to use nucleotide salvaging resulted in resistance to
      DHFR inhibitors. CONCLUSION: In summary, our data suggest that the genetic
      background in melanoma cells influences the response to inhibitors blocking de
      novo DNA synthesis, and that defining the RAS mutation status could be used to
      stratify patients for the use of antifolate drugs.

PMID- 24941945
TI  - A population genetic window into the past and future of the walleye Sander
      vitreus: relation to historic walleye and the extinct "blue pike" S. v.
      "glaucus".
AB  - BACKGROUND: Conserving genetic diversity and local adaptations are management
      priorities for wild populations of exploited species, which increasingly are
      subject to climate change, habitat loss, and pollution. These constitute growing
      concerns for the walleye Sander vitreus, an ecologically and economically
      valuable North American temperate fish with large Laurentian Great Lakes'
      fisheries. This study compares genetic diversity and divergence patterns across
      its widespread native range using mitochondrial (mt) DNA control region sequences
      and nine nuclear DNA microsatellite (MUsat) loci, examining historic and
      contemporary influences. We analyze the genetic and morphological characters of a
      putative endemic variant- "blue pike" S. v. "glaucus" -described from Lakes Erie
      and Ontario, which became extinct. Walleye with turquoise-colored mucus also are
      evaluated, since some have questioned whether these are related to the "blue
      pike". RESULTS: Walleye populations are distinguished by considerable genetic
      divergence (mean FST mtDNA = 0.32 +/- 0.01, MUsat = 0.13 +/- 0.00) and
      substantial diversity across their range (mean heterozygosity mtDNA = 0.53 +/-
      0.02, MUsat = 0.68 +/- 0.03). Southern populations markedly differ, possessing
      unique haplotypes and alleles, especially the Ohio/New River population that
      houses the oldest haplotype and has the most pronounced divergence. Northern
      formerly glaciated populations have greatest diversity in Lake Erie (mean
      heterozygosity mtDNA = 0.79 +/- 0.00, MUsat = 0.72 +/- 0.01). Genetic diversity
      was much less in the historic Lake Erie samples from 1923-1949 (mean
      heterozygosity mtDNA = 0.05 +/- 0.01, MUsat = 0.47 +/- 0.06) than today. The
      historic "blue pike" had no unique haplotypes/alleles and there is no evidence
      that it comprised a separate taxon from walleye. Turquoise mucus walleye also
      show no genetic differentiation from other sympatric walleye and no
      correspondence to the "blue pike". CONCLUSIONS: Contemporary walleye populations
      possess high levels of genetic diversity and divergence, despite habitat
      degradation and exploitation. Genetic and previously published tagging data
      indicate that natal homing and spawning site philopatry led to population
      structure. Population patterns were shaped by climate change and drainage
      connections, with northern ones tracing to post-glacial recolonization. Southerly
      populations possess unique alleles and may provide an important genetic
      reservoir. Allelic frequencies of Lake Erie walleye from ~70-90 years ago
      significantly differed from those today, suggesting population recovery after
      extensive habitat loss, pollution, and exploitation. The historic "blue pike" is
      indistinguishable from walleye, indicating that taxonomic designation is not
      warranted.

PMID- 24941946
TI  - Cost effectiveness of a pentavalent rotavirus vaccine in Oman.
AB  - BACKGROUND: Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in
      young children in Oman, incurring substantial healthcare and economic burden. We
      propose to formally assess the potential cost effectiveness of implementing
      universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the
      health care burden and costs associated with rotavirus gastroenteritis (RGE) in
      Oman METHODS: A Markov model was used to compare two birth cohorts, including
      children who were administered the RV5 vaccination versus those who were not, in
      a hypothetical group of 65,500 children followed for their first 5 years of life
      in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations,
      emergency department (ED) and office visits, and days of parental work loss for
      children receiving the vaccine was based on the results of the Rotavirus Efficacy
      and Safety Trial (REST). The outcome of interest was cost per quality-adjusted
      life year (QALY) gained from health care system and societal perspectives.
      RESULTS: A universal RV5 vaccination program is projected to reduce,
      hospitalizations, ED visits, outpatient visits and parental work days lost due to
      rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of
      RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani
      Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR
      (3,481,340 USD) in direct medical costs. However, with the introduction of RV5,
      direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per
      QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective.
      An RV5 vaccination program would be considered cost saving, from the societal
      perspective. CONCLUSIONS: Universal RV5 vaccination in Oman is likely to
      significantly reduce the health care burden and costs associated with rotavirus
      gastroenteritis and may be cost-effective from the payer perspective and cost
      saving from the societal perspective.

PMID- 24941947
TI  - Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration.
AB  - The study of neurogenesis during chronic neurodegeneration is crucial in order to
      understand the intrinsic repair mechanisms of the brain, and key to designing
      therapeutic strategies. In this study, using an experimental model of progressive
      chronic neurodegeneration, murine prion disease, we define the temporal dynamics
      of the generation, maturation and integration of new neurons in the hippocampal
      dentate gyrus, using dual pulse-chase, multicolour gamma-retroviral tracing,
      transmission electron microscopy and patch-clamp. We found increased neurogenesis
      during the progression of prion disease, which partially counteracts the effects
      of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine
      arabinoside, and helps to preserve the hippocampal function. Evidence obtained
      from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and
      Alzheimer's disease patients, also suggests increased neurogenic activity. These
      results open a new avenue into the exploration of the effects and regulation of
      neurogenesis during chronic neurodegeneration, and offer a new model to reproduce
      the changes observed in human neurodegenerative diseases. 

PMID- 24941949
TI  - High levels of multiresistance in quinolone resistant urinary tract isolates of
      Escherichia coli from Norway; a non clonal phenomen?
AB  - BACKGROUND: The problem of emerging ciprofloxacin resistance is compounded by its
      frequent association with multiresistance, the reason for which is not fully
      understood. In this study we compare multiresistance, clonal similarities and
      phylogenetic group in urinary tract isolates of Escherichia coli sensitive and
      resistant to the quinolone antimicrobials nalidixic acid and ciprofloxacin.
      RESULTS: Quinolone resistant isolates were more resistant to non-quinolone
      antibiotics than sensitive isolates, with resistance to ampicillin, mecillinam,
      sulphonamide, trimethoprim, tetracycline, kanamycin and chloramphenicol
      significantly increased. Fifty-one percent of quinolone-resistant isolates were
      multiresistant. Although multiresistance was most prevalent (63%) in isolates
      showing high-level ciprofloxacin resistance, it was still highly prevalent (41%)
      in nalidixic acid resistant isolates with low-level ciprofloxacin resistance.
      Multiresistance was more frequent among singleton isolates (61%) than clonal
      isolates (40%) of quinolone resistant Escherichia coli. Ciprofloxacin resistance
      was associated with certain specific clones, among them the globally distributed
      clonal Group A. However, there was no significant difference in the overall
      degree of clonality between quinolone sensitive and resistant isolates.
      Ciprofloxacin resistance was positively associated with phylogroup D and
      negatively associated with phylogroup B2. This correlation was not associated
      with clonal isolates. CONCLUSION: This study supports earlier findings of
      association between ciprofloxacin resistance and resistance to other antibiotics.
      The prevalence of multiresistance in quinolone-resistant isolates that have not
      yet developed high-level ciprofloxacin resistance suggest that multiresistance
      arises early in the development of quinolone resistance. This is consistent with
      exposure to quinolones causing quinolone resistance by mutations and mobilization
      of multiresistance elements by induction of the SOS response. The spread of
      clones seems to be less important than previously reported in regard to emergence
      of quinolone resistance and multiresistance as both are associated primarily with
      singleton isolates.

PMID- 24941948
TI  - Vulnerability of the ventral language network in children with focal epilepsy.
AB  - Children with focal epilepsy are at increased risk of language impairment, yet
      the neural substrate of this dysfunction is not yet known. Using functional
      magnetic resonance imaging we investigated the impact of focal epilepsy on the
      developing language system using measures of network topology (spatial
      organization of activation) and synchrony (functional connectivity). We studied
      healthy children (n = 48, 4-12 years, 24 females) and children with focal
      epilepsy (n = 21, 5-12 years, nine females) with left hemisphere language
      dominance. Participants performed an age-adjusted auditory description decision
      task during functional magnetic resonance imaging, to identify perisylvian
      language regions. Mean signal change was extracted from eight left perisylvian
      regions of interest and compared between groups. Paired region of interest
      functional connectivity analysis was performed on time course data from the same
      regions, to investigate left network synchrony. Two principal component analyses
      were performed to extract (i) patterns of activation (using mean signal change
      data); and (ii) patterns of synchronized regions (using functional connectivity
      data). For both principal component analyses two components (networks) were
      extracted, which mapped onto the functional anatomy of dorsal and ventral
      language systems. Associations among network variables, age, epilepsy-related
      factors and verbal ability were assessed. Activated networks were affected by age
      and epilepsy [F(2,60) = 3.74, P = 0.03]: post hoc analyses showed, for healthy
      children, activation in both ventral and dorsal networks decreased with age (P =
      0.02). Regardless of age and task performance, children with epilepsy showed
      reduced activation of the ventral network (P < 0.001). They also showed a trend
      for increased activation of the dorsal network (P = 0.08) associated with
      improved task performance (r = 0.62, P = 0.008). Crucially, decreased activation
      of the ventral network in patients predicted poorer language outcome ([Formula:
      see text] = 0.47, P = 0.002). This suggests childhood onset epilepsy
      preferentially alters maturation of the ventral language system, and this is
      related to poorer language ability. 

PMID- 24941950
TI  - Volume-Based Feeding in the Critically Ill Patient.
AB  - INTRODUCTION: Critically ill patients placed on enteral nutrition (EN) are
      usually underfed. A volume-based feeding (VBF) protocol designed to adjust the
      infusion rate to make up for interruptions in delivery should provide a greater
      volume of EN than the more common fixed hourly rate-based feeding (RBF) method.
      METHODS: This single-center, randomized (3:1; VBF/RBF) prospective study
      evaluated critically ill patients on mechanical ventilation expected to receive
      EN for >= 3 days. Once goal rate was achieved, the randomized feeding strategy
      was implemented. In the VBF group, physicians used a total goal volume of feeds
      to determine an hourly rate. For the RBF group, physicians determined a constant
      hourly rate of infusion to meet goal feeds. RESULTS: Sixty-three patients were
      enrolled in the study with a mean age of 52.6 years (60% male). Six patients were
      excluded after randomization because of early extubation. The VBF group (n = 37)
      received 92.9% of goal caloric requirements with a mean caloric deficit of -776.0
      kcal compared with the RBF group (n = 20), which received 80.9% of goal calories
      (P = .01) and a caloric deficit of -1933.8 kcal (P = .01). Uninterrupted EN was
      delivered for 51.7% of all EN days in VFB patients compared with 54.5% in RBF
      patients. On days when feeding was interrupted, VFB patients overall received a
      mean 77.6% of goal calories (while RBF patients received 61.5% of goal calories,
      P = .001). No vomiting, regurgitation, or feeding intolerance occurred due to
      VBF. CONCLUSIONS: A VBF strategy is safe and improves delivery to better meet
      caloric requirements than the standard more commonly used rate-based strategy.

PMID- 24941951
TI  - High-Fiber Orange Juice as a Nutrition Supplement in Women: A Randomized, Double
      Blind, Placebo-Controlled Study of Tolerance and Effectiveness.
AB  - BACKGROUND: The daily consumption of dietary fiber is frequently below suggested
      recommendations. Using a double-blind, controlled, randomized study, we assessed
      the efficiency and tolerance of a fiber-enriched orange juice to supplement fiber
      intake in women. MATERIALS AND METHODS: After 1 week of noninterventional
      observation, 192 healthy adult women ingested 400 mL of orange juice for 21 days,
      which either was not (placebo group) or was enriched with fiber (fiber group).
      Orange juice ingestion was registered daily and controlled for each week during
      the study period. Macronutrient, fiber, and energy intake were determined using a
      3-day food record, validated food chemical composition databases, and the "Pro
      Diet" software. Gastrointestinal symptoms were self-evaluated daily by scoring 4
      grades of symptom intensity and using a visual analog scale to grade pain
      severity. RESULTS: No changes were observed for macronutrient and energy
      ingestion. For the placebo group (n = 97), the total fiber intake record was
      under the daily recommended value. In contrast, the fiber group (n = 95)
      displayed higher comparative values of total and soluble fiber consumption (P <=
      .001), achieving the daily recommended values of fiber intake. Both groups
      reported an increased frequency of slight bloating and rumbles over time (P <=
      .05). The fiber group also experienced a higher frequency of slight flatulence
      over time (P = .002). CONCLUSION: Consumption of fiber-enriched orange juice was
      efficient to achieve the daily fiber intake recommendation for women, was not
      accompanied by intense adverse events, and may represent a suitable method to
      supplement fiber intake in woman.

PMID- 24941952
TI  - Perceptions of health professionals towards the management of back pain in the
      context of work: a qualitative study.
AB  - BACKGROUND: Musculoskeletal complaints have a significant impact on work in terms
      of reduced productivity, sickness absence and long term incapacity for work. This
      study sought to explore GPs' and physiotherapists' perceptions of sickness
      certification in patients with musculoskeletal problems. METHODS: Eleven (11) GPs
      were sampled from an existing general practice survey, and six (6)
      physiotherapists were selected randomly using 'snowball' sampling techniques,
      through established contacts in local physiotherapy departments. Semi-structured
      qualitative interviews were conducted with respondents lasting up to 30 minutes.
      The interviews were audio recorded and transcribed verbatim, following which they
      were coded using N-Vivo qualitative software and analysed thematically using the
      constant comparative methodology, where themes were identified and contrasted
      between and within both groups of respondents. RESULTS: Three themes were
      identified from the analysis: 1) Approaches to evaluating patients' work problems
      2) Perceived ability to manage 'work and pain', and 3) Policies and penalties in
      the work-place. First, physiotherapists routinely asked patients about their job
      and work difficulties using a structured (protocol-driven) approach, whilst GPs
      rarely used such structured measures and were less likely to enquire about
      patients' work situation. Second, return to work assessments revealed a tension
      between GPs' gatekeeper and patient advocacy roles, often resolved in favour of
      patients' concerns and needs. Some physiotherapists perceived that GPs' decisions
      could be influenced by patients' demand for a sick certificate and their close
      relationship with patients made them vulnerable to manipulation. Third, the
      workplace was considered to be a specific source of strain for patients acting as
      a barrier to work resumption, and over which GPs and physiotherapists could
      exercise only limited control. CONCLUSION: We conclude that healthcare
      professionals need to take account of patients' work difficulties, their own
      perceived ability to offer effective guidance, and consider the 'receptivity' of
      employment contexts to patients' work problems, in order to ensure a smooth
      transition back to work.

PMID- 24941953
TI  - Quantifying selection in immune receptor repertoires.
AB  - The efficient recognition of pathogens by the adaptive immune system relies on
      the diversity of receptors displayed at the surface of immune cells. T-cell
      receptor diversity results from an initial random DNA editing process, called VDJ
      recombination, followed by functional selection of cells according to the
      interaction of their surface receptors with self and foreign antigenic peptides.
      Using high-throughput sequence data from the beta-chain of human T-cell
      receptors, we infer factors that quantify the overall effect of selection on the
      elements of receptor sequence composition: the V and J gene choice and the length
      and amino acid composition of the variable region. We find a significant
      correlation between biases induced by VDJ recombination and our inferred
      selection factors together with a reduction of diversity during selection. Both
      effects suggest that natural selection acting on the recombination process has
      anticipated the selection pressures experienced during somatic evolution. The
      inferred selection factors differ little between donors or between naive and
      memory repertoires. The number of sequences shared between donors is well
      predicted by our model, indicating a stochastic origin of such public sequences.
      Our approach is based on a probabilistic maximum likelihood method, which is
      necessary to disentangle the effects of selection from biases inherent in the
      recombination process. 

PMID- 24941955
TI  - HBx induces hypomethylation of distal intragenic CpG islands required for active
      expression of developmental regulators.
AB  - Epigenetic alterations caused by viral oncoproteins are strong initiation factors
      for cancer development, but their mechanisms are largely unknown. To identify the
      epigenetic effects of viral hepatitis B virus X (HBx) that lead to hepatocellular
      carcinoma (HCC), we profiled the DNA methylomes of normal and HBx transgenic
      mouse liver. Intriguingly, severe hypomethylation of intragenic CpG islands
      (CGIs) was observed in HBx liver before the full development of HCC. Normally,
      these CGIs were highly methylated (mCGIs) by the DNMT3L complex and marked with
      epigenetic signatures associated with active expression, such as H3K36me3.
      Hypomethylation of mCGI was caused by the downregulation of Dnmt3L and Dnmt3a due
      to HBx bound to their promoters, along with HDAC1. These events lead to the
      downregulation of many developmental regulators that could facilitate
      tumorigenesis. Here we provide an intriguing epigenetic regulation mediated by
      mCGI that is required for cell differentiation and describe a previously
      unidentified epigenetic role for HBx in promoting HCC development. 

PMID- 24941957
TI  - Differences in survivability under starvation conditions among four species of
      purple nonsulfur phototrophic bacteria.
AB  - Survivability under carbon-starvation conditions was investigated in four species
      of purple phototrophic bacteria: Rhodopseudomonas palustris, Rhodobacter
      sphaeroides, Rhodospirillum rubrum, and Rubrivivax gelatinosus. All these test
      organisms survived longer in the light than in the dark. ATP levels in the
      cultures were maintained in the light, which indicated that survivability was
      supported by photosynthesis. Survivability and tolerance against hypertonic
      stress in the dark was higher in Rhodopseudomonas palustris, which is widely
      distributed in natural environments including soils, than in the three other
      species. 

PMID- 24941956
TI  - High-dose rate brachytherapy in localized penile cancer: short-term clinical
      outcome analysis.
AB  - PURPOSE: To assess clinical outcomes of high-dose rate interstitial brachytherapy
      (HIB) in localized penile carcinoma. MATERIAL AND METHODS: From 03/2006 to
      08/2013, patients with biopsy-proven T1-T2 (<4 cm) non-metastatic localized
      penile squamous cell carcinoma underwent HIB. Under general anaesthesia, after
      Foley catheter placement, needles were placed in the target volume using a
      dedicated template. Planification was carried out with a post-implant CT-scan to
      deliver a total dose of 36 Gy in 9 fractions over 5 days (in adjuvant setting) or
      39 Gy in 9 fractions over 5 days (as monotherapy). Dose-volume adaptation was
      manually achieved using graphical optimization. Dosimetric data and clinical
      outcomes were retrospectively analyzed. Toxicities were graded using the CTC
      v4.0. RESULTS: With a median follow-up of 27 months [5.1-83], 12 patients
      including 8 T1a, 3 T1b and 1 T2 N0 underwent HIB (sole therapy: 11 pts; adjuvant:
      1 pt). The actuarial 5-year relapse-free, cause-specific and overall survival
      rates were 83%, 100% and 78% respectively. Comparing pre and post treatment
      evaluation, no IPSS or IIEF-5 changes were reported. Dermatitis was reported
      systematically 1 month after HIB including 6 G1, 5 G2 and 1 G3. Only 1
      experienced long-term G3 successfully treated with hyperbaric oxygen therapy. One
      urethral meatus stenosis G3 required meatotomy. CONCLUSION: In selected patients
      with T1-T2 localized penile cancer, HIB may be considered as an optional
      conservative therapy. Longer follow-up is needed to confirm these encouraging
      preliminary results.

PMID- 24941960
TI  - Use of cyproheptadine in young children with feeding difficulties and poor growth
      in a pediatric feeding program.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and safety of
      cyproheptadine (CY) use in infants and young children with poor growth treated at
      our multidisciplinary pediatric feeding program, and to describe changes in their
      weight and feeding behaviors. METHODS: A retrospective chart review of children
      treated with CY from January 2007 to July 2011 was performed. Demographic data,
      medical diagnosis, adverse effects of the drug, and changes in mealtime behaviors
      were extracted from the patients' medical records. For each patient who received
      the CY, weight-for-age z scores (WtZ) were calculated before and during
      treatment. Repeated-measures mixed model was used to analyze the pattern of
      change in WtZ over time and between groups. Differences in mean WtZ were tested
      between patients regularly receiving CY and a naturally conceived comparison
      group. RESULTS: Of the 127 patients in treatment owing to poor weight gain who
      received the CY, 82 took the medication regularly as prescribed in combination
      with our interventional program. For these patients, the majority of the parents
      (96%) reported a positive change in mealtime and feeding behaviors. A significant
      improvement in mean WtZ was observed after starting CY when compared with the WtZ
      before treatment for those patients regularly receiving the medication. This
      effect was independent of patients' age and/or presence of an underline medical
      problem. No significant differences in mean WtZ were observed over time within
      the comparison group. CONCLUSIONS: In our experience, the use of CY in
      combination with a specialized multidisciplinary interventional program is a safe
      and effective therapy in infants and young children with low appetite and poor
      growth.

PMID- 24941958
TI  - Lactulose: mannitol diagnostic test by HPLC and LC-MSMS platforms: considerations
      for field studies of intestinal barrier function and environmental enteropathy.
AB  - OBJECTIVES: The lactulose:mannitol (L:M) diagnostic test is frequently used in
      field studies of environmental enteropathy (EE); however, heterogeneity in test
      administration and disaccharide measurement has limited the comparison of results
      between studies and populations. We aim to assess the agreement between L:M
      measurement between high-performance liquid chromatography with pulsed
      amperometric detection (HPLC-PAD) and liquid chromatography-tandem mass
      spectrometry (LC-MSMS) platforms. METHODS: The L:M test was administered in a
      cohort of Peruvian infants considered at risk for EE. A total of 100 samples were
      tested for lactulose and mannitol at 3 independent laboratories: 1 running an
      HPLC-PAD platform and 2 running LC-MSMS platforms. Agreement between the
      platforms was estimated. RESULTS: The Spearman correlation between the 2 LC-MSMS
      platforms was high (rho >= 0.89) for mannitol, lactulose, and the L:M ratio. The
      correlation between the HPLC-PAD platform and LC-MSMS platform was rho = 0.95 for
      mannitol, rho = 0.70 for lactulose, and rho = 0.43 for the L:M ratio. In
      addition, the HPLC-PAD platform overestimated the lowest disaccharide
      concentrations to the greatest degree. CONCLUSIONS: Given the large analyte
      concentration range, the improved accuracy of LC-MSMS has important consequences
      for the assessment of lactulose and mannitol following oral administration in
      populations at risk for EE. We recommend that researchers wishing to implement a
      dual-sugar test as part of a study of EE use an LC-MSMS platform to optimize the
      accuracy of results and increase comparability between studies.

PMID- 24941961
TI  - A Rare "Neurological" Cause for Childhood Abdominal Pain.

PMID- 24941962
TI  - Coronary sinus lead extraction in CRT patients with CIED-related infection:
      risks, implications and outcomes.
AB  - AIM: The aim of the study was to examine risks, implications and outcomes of
      coronary sinus (CS) lead extraction in patients with infections of cardiac
      resynchronization therapy (CRT) systems. METHODS: The study included 40 (65.5 +/-
      11.1 years; 80% male) transvenous CS lead extraction procedures performed between
      2000-2011. Nine (22.5%) patients suffered from infection and included one sepsis
      (11.1%), two (22.2%) of lead and valve endocarditis, and four (44.4%) cases of
      pocket infection. CS lead extraction in the infection subgroup was performed
      between 14 days and more than five years after the last CIED-related surgical
      procedure. RESULTS: Totally 42 CS and 35 non-CS leads were extracted. Leads
      extracted in the infection subgroup were significantly longer in situ (49.7 +/-
      30.7 months) compared to the non-infection subgroup (19.2 +/- 28.6 months).
      Extraction in infected patients required more aggressive methods and longer
      exposure to radiation than non-infected. Procedural success without major
      complications was achieved in all patients. Minor post-procedural complications
      occurred in four (44.4%) of the infected and one (3.2%) of the non-infected
      patients and were surgical-related in three cases. Overall hospitalization times
      were significantly longer for the infection than for the non-infection subgroup
      (21.4 +/- 15 versus 9.6 +/- 6.9 days). CONCLUSION: Our results support the
      concept of complete CIED-system removal in CIED-associated infection, regardless
      of whether or not infection appears to be limited to the generator pocket site,
      despite risk of heart failure, patient frailty and a high level of comorbidity.
      An interdisciplinary approach encompassing appropriate diagnostic, procedural and
      safety standards allows CS lead extraction in this high-risk subpopulation to be
      performed with excellent outcomes and low complication rates.

PMID- 24941963
TI  - Sonographic detection of ulnar nerve compression during elbow extension.

PMID- 24941964
TI  - Re: Impact of pressure ulcers on outcomes in inpatient rehabilitation facilities.

PMID- 24941965
TI  - First report on joint use of a Da Vinci(r) surgical system with transfer of
      surgical know-how between two public hospitals.
AB  - INTRODUCTION: The costs of a Da Vinci(r) device for robot- assisted surgery, in
      particular for robot-assisted radical prostatectomy (RARP), can be a considerable
      issue for hospitals with limited caseloads. MATERIALS AND METHODS: Since January
      2011 the cantonal hospitals of Lucerne and St. Gallen (Switzerland) have shared a
      four-arm Da Vinci(r) device, transferring the surgical know-how by a Lucerne
      teaching surgeon to a St. Gallen surgeon. Complete pre- and perioperative data,
      including 3-month surgical RARP outcomes, were prospectively documented. For
      statistical analysis, Wilcoxon, exact Poisson and chi(2) tests were used.
      RESULTS: During the first year, the two hospitals (61 RARP patients in Lucerne,
      19 RARP patients in St. Gallen) did not differ significantly in preoperative,
      perioperative or oncological and functional results except for prostate volume
      (median 33 [interquartile range 24-40] vs. 40 [interquartile range 33-57] ml; p =
      0.02), operation time (mean 252 +/- 49 vs. 351 +/- 50 min; p = 0.0001), number of
      lymph nodes removed (median 16 [interquartile range 13-21] vs. 15 [interquartile
      range 8-16] nodes; p = 0.02), biopsy (p = 0.04) and specimen Gleason scores (p =
      0.03), and length of hospital stay (median 8 [interquartile range 7-14] vs. 9
      [interquartile range 8-18] days; p < 0.01). CONCLUSIONS: Da Vinci(r) device
      sharing with transfer of surgical know-how can reduce the costs of RARP without
      compromising surgical outcomes, even at the beginning of the learning curve.

PMID- 24941966
TI  - Instant reocclusion following mechanical thrombectomy of in situ thromboocclusion
      and the role of low-dose intra-arterial tirofiban.
AB  - BACKGROUND: An in situ thromboocclusion (IST) is defined as an infarct
      extensively involving all or most of a stenosed arterial territory, which is one
      major stroke mechanism related to intracranial atherosclerosis (ICAS). We focused
      on ISTs occurring in major cerebral arteries and analyzed their rate of instant
      reocclusion during mechanical thrombectomy (MT) compared with non-ISTs. Also, we
      introduced a treatment strategy of low-dose intra-arterial tirofiban
      administration to prevent such reocclusion following repeat recanalization, and
      evaluated its safety and efficacy. METHODS: We analyzed 168 consecutive patients
      treated with MT over a 2-year period from May 2011 to April 2013. During MT, if
      angiography following a successful recanalization showed stenosis at the
      occlusion site, we performed additional angiographic runs every 10 min for 30 min
      after the recanalization. Then, if angiography revealed reocclusion, we performed
      a repeat recanalization, using the same MT technique but additionally followed by
      low-dose intra-arterial tirofiban infusion. Time-of-flight MR angiography or CT
      angiography was performed to confirm any underlying ICAS at the occlusion site 5
      7 days after the procedure. The patients who had confirmed underlying ICAS were
      included in the IST cohort. RESULTS: Of 168 enrolled patients, we excluded 36 who
      could not be checked for underlying ICAS at the occlusion site for one of the
      following reasons: recanalization failure (n = 11), rescue stenting after
      tirofiban failure (n = 5) and lack of follow-up vascular imaging (n = 20). The
      incidence of IST was 30.3% (40/132). All IST patients were confirmed to have
      underlying ICAS by follow-up vascular imaging. Instant reocclusion after
      successful recanalization was significantly more frequent in the IST cohort
      [26/40 (65%) vs. 3/92 (3.3%); p < 0.001]. Regarding the efficacy of low-dose
      intra-arterial tirofiban infusion, 85.7% of the reocclusion patients finally
      achieved a thrombolysis in cerebral infarction score 2/3 recanalization, but in
      the remaining 14.3% of the cases, the condition was refractory to the procedure
      and required rescue stenting. There were no cases of symptomatic intracranial
      hemorrhage following the procedure. CONCLUSIONS: In situ thromboocclusion was
      characterized by a significantly higher chance of instant reocclusion during MT.
      In such cases, low-dose intra-arterial tirofiban administration may be effective
      and safe. However, future confirmation by prospective multicenter trials seems
      necessary.

PMID- 24941969
TI  - Surface nanostructures in manganite films.
AB  - Ultrathin manganite films are widely used as active electrodes in organic
      spintronic devices. In this study, a scanning tunnelling microscopy (STM)
      investigation with atomic resolution revealed previously unknown surface features
      consisting of small non-stoichiometric islands. Based upon this evidence, a new
      mechanism for the growth of these complex materials is proposed. It is suggested
      that the non-stoichiometric islands result from nucleation centres that are below
      the critical threshold size required for stoichiometric crystalline growth. These
      islands represent a kinetic intermediate of single-layer growth regardless of the
      film thickness, and should be considered and possibly controlled in manganite
      thin-film applications. 

PMID- 24941967
TI  - Breast cancer risk assessment using genetic variants and risk factors in a
      Singapore Chinese population.
AB  - INTRODUCTION: Genetic variants for breast cancer risk identified in genome-wide
      association studies (GWAS) in Western populations require further testing in
      Asian populations. A risk assessment model incorporating both validated genetic
      variants and established risk factors may improve its performance in risk
      prediction of Asian women. METHODS: A nested case-control study of female breast
      cancer (411 cases and 1,212 controls) within the Singapore Chinese Health Study
      was conducted to investigate the effects of 51 genetic variants identified in
      previous GWAS on breast cancer risk. The independent effect of these genetic
      variants was assessed by creating a summed genetic risk score (GRS) after
      adjustment for body mass index and the Gail model risk factors for breast cancer.
      RESULTS: The GRS was an independent predictor of breast cancer risk in Chinese
      women. The multivariate-adjusted odds ratios (95% confidence intervals) of breast
      cancer for the second, third, and fourth quartiles of the GRS were 1.26 (0.90 to
      1.76), 1.47 (1.06 to 2.04) and 1.75 (1.27 to 2.41) respectively (P for
      trend<0.001). In addition to established risk factors, the GRS improved the
      classification of 6.2% of women for their absolute risk of breast cancer in the
      next five years. CONCLUSIONS: Genetic variants on top of conventional risk
      factors can improve the risk prediction of breast cancer in Chinese women.

PMID- 24941968
TI  - Vanillin formation from ferulic acid in Vanilla planifolia is catalysed by a
      single enzyme.
AB  - Vanillin is a popular and valuable flavour compound. It is the key constituent of
      the natural vanilla flavour obtained from cured vanilla pods. Here we show that a
      single hydratase/lyase type enzyme designated vanillin synthase (VpVAN) catalyses
      direct conversion of ferulic acid and its glucoside into vanillin and its
      glucoside, respectively. The enzyme shows high sequence similarity to cysteine
      proteinases and is specific to the substitution pattern at the aromatic ring and
      does not metabolize caffeic acid and p-coumaric acid as demonstrated by coupled
      transcription/translation assays. VpVAN localizes to the inner part of the
      vanilla pod and high transcript levels are found in single cells located a few
      cell layers from the inner epidermis. Transient expression of VpVAN in tobacco
      and stable expression in barley in combination with the action of endogenous
      alcohol dehydrogenases and UDP-glucosyltransferases result in vanillyl alcohol
      glucoside formation from endogenous ferulic acid. A gene encoding an enzyme
      showing 71% sequence identity to VpVAN was identified in another vanillin
      producing plant species Glechoma hederacea and was also shown to be a vanillin
      synthase as demonstrated by transient expression in tobacco. 

PMID- 24941970
TI  - Conversion of adjustable gastric banding to Roux-en-Y gastric bypass: not as
      optimal as primary gastric bypass?

PMID- 24941971
TI  - [In Process Citation].

PMID- 24941972
TI  - [In Process Citation].

PMID- 24941973
TI  - [ARIA Mexico 2014. Adaptation of the Clinical Practice Guide ARIA 2010 for
      Mexico. Methodology ADAPTE].
AB  - BACKGROUND: The global prevalence of allergic rhinitis is high. International
      Study of Asthma and Allergies in Childhood (ISAAC) Phase III reports a total
      estimated prevalence of 4.6% in Mexico. There is evidence based on allergic
      rhinitis Clinical Practice Guidelines (CPG), but its promotion, acceptance and
      application is not optimal or adequate in Mexico. OBJECTIVE: To generate a
      guideline for the treatment of allergic rhinitis and its impact on asthma by
      adaptating the 2010 ARIA Guideline to Mexican reality, through a transculturation
      process applying the ADAPTE methodology. PATIENTS AND METHOD: Using the ADAPTE
      Methodology, the original 2010 ARIA CPG recommendations were evaluated by the
      guideline development group (GDG) into which multiple medical specialities
      managing patients with allergic rhinitis were incoorporated. The GDG valorated
      the quality of 2010 ARIA, checked and translated key clinical questions.
      Moreover, the GDG adjusted recommendations, patient preferences and included
      comments in the context of the Mexican reality (safety, costs and cultural
      issues). To accomplish this, we ran Delphi panels with as many rounds as
      necessary to reach agreement. One extra question, not included in the original
      2010 ARIA, on the use of Nasal Lavages for AR was created sustained by a
      systematic literature review. RESULTS: A total of 45 questions from the original
      2010 ARIA were included and divided into six groups covering prevention, medical
      treatment, immunotherapy and alternative medicine to treat patients with allergic
      rhinitis with or without asthma. Most of the questions reached agreement in one
      or two rounds; one question required three rounds. CONCLUSIONS: An easy-to-use,
      adaptated, up-to-date and applicable allergic rhinitis guideline for Mexico is
      now available.

PMID- 24941975
TI  - Prostate cancer: an occupational hazard?

PMID- 24941974
TI  - Increased density of Demodex folliculorum mites in pregnancies with gestational
      diabetes.
AB  - OBJECTIVE: To investigate the presence of Demodex in patients with gestational
      diabetes and the impact of glucose regulation on Demodex density in gestational
      diabetes. SUBJECTS AND METHODS: The study population consisted of 33 patients
      with gestational diabetes and 30 pregnant women without gestational diabetes
      (control group). The age, parity, gestational age, and BMI of the study group
      were recorded and the patients were divided into 2 groups, i.e. those with
      regulated and unregulated glucose levels, according to their postprandial 1st-
      and 2nd-hour glucose values. A standardized skin surface biopsy method was used
      to determine if patients had Demodex folliculorum infestation (>5 mites/cm(2) of
      skin). RESULTS: Patients with gestational diabetes had a statistically
      significantly higher Demodex density compared to the control group (24.2 vs.
      3.3%; p < 0.001). Furthermore, a significantly higher proportion of gestational
      diabetes patients with unregulated glucose levels had a higher Demodex density
      compared to those in the regulated subgroup (6/19 vs. 2/14; p = 0.001).
      CONCLUSION: Our study revealed that the Demodex density was increased in
      gestational diabetes patients. Further, poor glucose regulation could be the
      mechanism responsible for the increased Demodex density in gestational diabetes
      patients with unregulated glucose levels compared to those with regulated glucose
      levels.

PMID- 24941977
TI  - Immunotherapy for high-grade glioma.
AB  - 4th Quadrennial Meeting of the World Federation of Neuro-Oncology in conjunction
      with the 18th Annual Meeting of the Society for Neuro-Oncology, San Francisco,
      CA, USA, 21-24 November 2013. Aside from temozolomide, there has been no major
      breakthrough for decades to improve outcome for high-grade glioma. Bevacizumab
      failed to show a survival advantage in two large studies - AVaglio and RTOG-0825 
      and no other novel chemotherapy agents seem to be appearing on the horizon for
      this universally fatal disease. Consequently, the neuro-oncology fraternity is
      turning to immunotherapy. This became apparent in this meeting, considering a
      number of delegates focused their attention to presentations on immunotherapy.
      The ReACT study demonstrated the safety and efficacy of the combination of a
      promising peptide vaccine, rindopepimut, and bevacizumab with longer survival
      seen in patients with a higher antibody titer. Several presentations reassured
      that dendritic cell-based immunotherapy is safe and can generate a lasting immune
      response. Employing gene therapy, increased intratumor 5-fluorouracil
      chemotherapy concentration can be achieved using TOCA 511, and temozolomide
      resistant transgenic lymphocytes could be produced through retroviral coding.
      Blocking immune checkpoints PDL-01, CTLA-4 and indoleamine 2,3-dioxygenase
      through monoclonal antibodies appears promising.

PMID- 24941978
TI  - Skeletal and cranio-facial signs in Gorlin syndrome from ancient Egypt to the
      modern age: sphenoid asymmetry in a patient with a novel PTCH1 mutation.
AB  - Gorlin syndrome is an autosomal dominant disorder linked to PTCH1 mutation,
      identified by a collection of clinical and radiologic signs. We describe the case
      of a family in which father and son fulfilled clear cut diagnostic criteria for
      Gorlin syndrome including multiple basal cell carcinomas, keratocystic
      odontogenic tumors, atypical skeletal anomalies and a novel PTCH1 germline
      mutation (c.1041delAA). Craniofacial and other skeletal anomalies displayed at 3D
      and helical CT scan were: macrocephaly, positional plagiocephaly, skull base and
      sphenoid asymmetry, bifidity of multiple ribs and giant multilocular odontogenic
      jaw cysts. Extensive multilamellar calcifications were found in falx cerebri,
      tentorium, falx cerebelli and in the atlanto-occipital ligament. The inclusion of
      bifid ribs as a novel major criteri may be useful for the recognition and
      characterization of misdiagnosed cases. 

PMID- 24941979
TI  - Vismodegib for the treatment of basal cell carcinoma: results and implications of
      the ERIVANCE BCC trial.
AB  - The need for effective treatment of patients with locally advanced or metastatic
      basal cell carcinoma (BCC), in conjunction with major advances in the elucidation
      of the molecular basis of this tumor has led to the advent of new targeted
      therapies - namely, hedgehog inhibitors. The rationale for their use in patients
      with advanced BCC is based on their inhibitory effect on the hedgehog pathway,
      which is aberrantly activated in BCCs due to mutations of its primary components,
      PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog
      pathway inhibitor that selectively inhibits SMO. The ERIVANCE BCC study is a
      Phase II, international, multicenter clinical trial evaluating the efficacy and
      safety of vismodegib 150 mg once daily in patients with locally advanced or
      metastatic BCC. Vismodegib has been approved for the treatment of adult patients
      with metastatic BCC, or with locally advanced BCC that has recurred following
      surgery or who are not candidates for surgery or radiation therapy. This article
      will outline the rationale, design and available results from the ERIVANCE BCC
      study and discuss the clinical implications of vismodegib in the management of
      patients with BCC. Challenges regarding vismodegib use include the recurrence of
      BCC after drug discontinuation, the development of acquired resistance, the
      dramatic efficacy in patients with Gorlin syndrome, and class-related drug
      toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the
      neoadjuvant setting prior to surgery, the potential use of alternate dosing
      regimens in order to limit chronic adverse events, as well as the identification
      of patients with BCC that are more likely to respond to this targeted therapy
      based on genotypic and/or phenotypic characteristics. 

PMID- 24941980
TI  - IMA901 for metastatic renal cell carcinoma in the context of new approaches to
      immunotherapy.
AB  - The promising option of immunotherapy for metastatic renal cell carcinoma has
      evolved from rather unspecific approaches to a specific activation of an anti
      tumor T-cell response. The latest step is a synthetic peptide vaccine called
      IMA901, which demonstrated a clear association between a provoked T-cell response
      and a prolonged overall survival. The results of IMA901 for the treatment of
      metastatic renal cell carcinoma are discussed together with new approaches to
      immunotherapy, such as local and systemic immunomodulation with adjuvants,
      checkpoint inhibitors, classical chemotherapeutics, such as cyclophosphamide or
      tyrosine kinase inhibitors. The capability of theses substances to modulate
      leukocytes subsets, such as myeloid-derived suppressor cells, Tregs or Th17
      cells, are outlined together with the possibility to combine them with tumor
      vaccination strategies to achieve a higher cancer specificity and immunogenicity.

PMID- 24941981
TI  - Elotuzumab for the treatment of multiple myeloma.
AB  - New agents are awaited for the treatment of multiple myeloma and research is
      ongoing for the development of monoclonal antibodies (MoAbs) targeting the tumor
      cells. One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb
      specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly
      expressed in plasma cells. Preclinical and clinical data on elotuzumab will be
      presented in this article. 

PMID- 24941983
TI  - Female fertility preservation in cancer patients: an instrumental tool for the
      envisioning a postdisease life.
AB  - AIM: To verify whether fertility preservation (FP) improves the way women
      contemplate their life after the disease. MATERIALS & METHODS: 285 cancer
      patients referred for FP counseling were prospectively studied. A standardized
      questionnaire was submitted to all participants. RESULTS: A total of 85 patients
      (39.0%) returned the questionnaire. None of the women who rejected the FP
      proposal after oncofertility counseling returned the questionnaire. The median
      age of responders was 29.1 years (range: 18-40 years). In total, 35 of them
      (41.1%) were single and 72 (84.7%) were childless. A total of 66 women (77.6%)
      reported that the possibility of preserving fertility was instrumental to
      improving their coping with the burden of treatments. Since 61.2% patients
      perceived their cryopreserved oocytes or embryos as future children or family,
      the projection in a postdisease life may be at play in this improved subjective
      experience of treatment. CONCLUSION: The present results indicate that the simple
      fact of undergoing FP improves the patients' subjective experience of cancer
      treatments.

PMID- 24941982
TI  - Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase.
AB  - Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's
      tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for
      B-cell survival and proliferation. In preclinical studies, ibrutinib bound to
      Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell
      receptor signaling, decreased B-cell activation and induction of apoptosis. In
      clinical studies, ibrutinib has been well-tolerated and has demonstrated profound
      anti-tumor activity in a variety of hematologic malignancies, most notably
      chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US
      FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib
      in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma
      and Waldenstrom's macrogobulinemia, in larger Phase III studies in CLL and MCL,
      and in combination studies with monoclonal antibodies and chemotherapy. Future
      studies will combine ibrutinib with other promising novel agents currently in
      development in hematologic malignancies.

PMID- 24941984
TI  - Potential value of rapid prostate-specific antigen decline in identifying primary
      resistance to abiraterone acetate and enzalutamide.
AB  - AIM: To identify factors predicting primary resistance to new-generation hormonal
      agents (NHAs), abiraterone acetate and enzalutamide in patients with castration
      resistant prostate cancer (CRPC). PATIENTS & METHODS: Our hospital has conducted
      two successive named patient NHA programs. A total of 57 patients with
      progressive CRPC previously treated with first-line docetaxel-based chemotherapy
      received standard NHA doses: abiraterone acetate 1000 mg once-daily combined with
      prednisone (5 mg twice daily) or enzalutamide 160 mg once-daily. Patients, who
      were assessed monthly to check their hematological parameters and prostate
      specific antigen (PSA) levels, also underwent imaging investigations every 3-4
      months. In total, 24 variables were assessed as potential predictors of primary
      NHA resistance. RESULTS: Univariate analysis indicated that baseline pain and
      lactate dehydrogenase levels, and PSA levels after 1 month's treatment were
      predictive of primary NHA resistance. Only the predictive value of PSA levels
      after 1 month of treatment was confirmed at multivariate analysis. This factor
      strongly predicted progression-free and overall survival. CONCLUSION: RESULTS
      suggest the use of a simple and rapid method of identifying patients with primary
      resistance to NHAs: patients not achieving a >= 50% reduction in PSA levels
      within the first treatment month should undergo intensive investigations to
      verify whether they have primary resistance to NHAs.

PMID- 24941986
TI  - Microwave ablation of benign thyroid nodules.
AB  - Microwave ablation (MWA) has become increasingly popular as a minimally invasive
      treatment for benign and malignant tumors of the liver, lung and kidney.
      Recently, two studies have attempted to apply the technique to debulk benign
      thyroid nodules and gained positive results. MWA of benign nodules demonstrated
      significant volume reductions, while solving nodule-related clinical problems.
      This article reviews the basic physics, therapeutic indications, patient
      preparation, devices, procedures, clinical results and complications of thyroid
      MWA. 

PMID- 24941985
TI  - Mdm2 protein expression is strongly associated with survival in malignant pleural
      mesothelioma.
AB  - AIMS: TP53 mutations are extremely rare in malignant pleural mesothelioma (MPM).
      In TP53 wild-type tumors, the functional p53 protein can be inactivated by MDM2.
      MATERIALS & METHODS: A total of 61 patient samples were tested for their Mdm2 and
      p53 protein expression levels via immunohistochemistry. RESULTS: This study
      demonstrates nuclear Mdm2 expression in three out of four mesothelioma cell lines
      and 21.3% of the MPM specimens investigated. After silencing of the MDM2 gene by
      siRNA in MPM cell lines, Mdm2 immunoexpression is lost and cells show changes
      indicative of severe damage. Mdm2 protein expression in MPM is detected in
      epithelioid and biphasic subtypes only and is significantly associated with poor
      survival compared with Mdm2-negative tumors. This may be explained by increased
      Mdm2 levels possibly leading to an increased ubiquitilation and proteasomal
      degradation of functional p53 protein. CONCLUSION: Expression of Mdm2 is a strong
      prognostic factor associated with shortened overall survival in MPM.

PMID- 24941987
TI  - Improving quality of life in female cancer survivors: current status and future
      questions.
AB  - Almost 14 million people in the USA alone have been diagnosed with cancer. Given
      the improvements in diagnosis and treatment, over 60% of patients are expected to
      survive 5 years or more from the point of diagnosis. Treatments for cancer may
      result in long-term issues including those that impact the physical, emotional,
      spiritual or social domains. However, how best to care for issues in survivors
      remains unclear. Although much attention has been focused on survivorship care
      plans and survivorship clinics, there are limited data to show they improve
      outcomes. This article reviews the issues in female cancer survivors that can
      occur following diagnosis and treatment and suggest strategies that may assist in
      management. Finally, we review the current views regarding the care of cancer
      survivors and suggest important issues that must be addressed so that we can
      reach our goal of improvement in the quality of life of this emerging population.

PMID- 24941989
TI  - Techniques in the prevention and management of seromas after breast surgery.
AB  - Seromas are the most frequent complications following breast surgery, resulting
      in significant discomfort and morbidity with possible delays in commencing
      adjuvant therapies. Varied clinical practices exist in the techniques employed to
      prevent and manage seromata. This article assesses published literature on the
      techniques employed in prevention of seroma formation following breast surgery,
      evaluating the different methodologies used. Although prevention is the best
      strategy, seromata remain problematic and we consider their management. The
      principle findings were that prevention is key to the management of seromata.
      Methods employed to prevent seromata include suction drainage, shoulder
      immobilization, quilting sutures, fibrin sealants and innovative measures of
      managing the axilla, among others. The evidence demonstrated that a combination
      of quilting and drains significantly reduces the incidence and volumes of
      seromata. These effects are sustained by minimizing use of electrocautery,
      alongside increasing frequencies of axillary sentinel lymph node biopsies and
      node sampling. The efficacy data on fibrin sealants is inconclusive and
      consequently should not be routinely used alone or accompanied by quilting
      sutures. Clinically significant seromas deemed 'symptomatic' by patients and
      complicating infected seromas should be aspirated. There are limited data on the
      recommended treatment of established seromas with a paucity of high-quality
      studies and further research involving randomized trials are indicated. 

PMID- 24941988
TI  - The role of miRNAs in cancer: from pathogenesis to therapeutic implications.
AB  - Cancer is still one of the dominating causes of deaths worldwide, although there
      have been important enhancements for detection and diagnosis of cancer recently.
      miRNAs are shown to participate in carcinogenesis of several types of tumors and
      their aberrant expression of miRNAs has been detected in cell lines, xenografts
      and clinical samples. miRNAs are thought to target and modulate the expression of
      more than 60% of human genes, which makes the expressional regulation by miRNAs
      the most abundant post-transcriptional regulation mode. Here, we have reviewed
      the most current literature to shed a light on the functions of miRNAs on human
      carcinogenesis. Possible roles of miRNAs in oncogenesis through both genetic and
      epigenetic changes occurring during cancer initiation, progression, invasion or
      metastasis are summarized. 

PMID- 24941990
TI  - Novel treatments for head and neck squamous cell carcinoma: preclinical
      identification and clinical investigation.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide.
      Classically, it is a disease related to tobacco and alcohol use; an increasing
      number of patients are being diagnosed with HNSCC caused by infection with the
      human papillomavirus. New deep-sequencing techniques have confirmed the
      importance of p53 and EGF receptor in HNSCC development, and have identified
      pathways of critical importance, such as PI3K/mTOR and NOTCH. Increasing
      knowledge of key molecular features has lead to new therapeutic avenues for
      HNSCC. Novel therapies under investigation in HNSCC include antibody and small
      molecule inhibitors of EGF receptor and its family members, PI3K inhibitors,
      antiangiogenic agents, immunotherapies and agents interacting with early
      developmental pathways such as Hedgehog. 

PMID- 24941991
TI  - First-line therapeutic options for advanced non-small-cell lung cancer in the
      molecular medicine era.
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide in both
      sexes, expected to account, in the near future, for more than 30% of all cancer
      related deaths. Recently, improvements in the systemic therapy of non-small-cell
      lung cancer according to histology and tumor molecular characteristics led to a
      progressive prolongation of survival, more clinically meaningful in selected
      groups of patients with tumors harboring specific genomic alterations. As the
      search for individualized therapeutic approaches could represent one of the
      potential ways to improve survival expectancy of non-small-cell lung cancer
      patients with advanced disease stage, the aim of this review is to discuss how
      currently to select the best front-line therapeutic strategy. 

PMID- 24941992
TI  - Frontiers in clinical and molecular diagnostics and staging of metastatic clear
      cell renal cell carcinoma.
AB  - The last few years have brought advances in the understanding of the molecular
      biology of metastatic clear cell renal cell carcinoma (RCC). Both preclinical
      research and clinical trials brought together results from the latest
      advancements in RCC diagnostic and staging. Understanding of the complex
      molecular alterations involved in the development and progression of RCC enables
      development of immunohistochemical and genetic diagnostic tools and is also
      opening the doors for experimental targeted therapies. At the same time,
      improvements of medical and molecular imaging improves the sensitivity and
      specificity of metastatic disease diagnosis. Moreover, independent validation of
      molecular profiles across high-throughput platforms, methods, laboratories and
      cancer populations has recently been successfully performed in RCC. Generation of
      informative, clinical diagnostic tools is likely to contribute to development of
      novel personalized diagnostic and treatment protocols and ensure prolonged
      survival of RCC patient in the near future. 

PMID- 24941993
TI  - Nerve regeneration and functional recovery by collagen-binding brain-derived
      neurotrophic factor in an intracerebral hemorrhage model.
AB  - Brain-derived neurotrophic factor (BDNF) exerts therapeutic effects following
      intracerebral hemorrhage (ICH). However, it is difficult to maintain sufficient
      concentrations in the hemorrhage hemisphere. We demonstrated previously that BDNF
      fused to a collagen-binding domain (CBD) could bind to collagen in the
      ventricular ependyma and stimulate cell proliferation in the subventricular zone
      (SVZ). In this study, we verified the therapeutic effects of CBD-BDNF in the rat
      ICH model induced by bacterial collagenase by injecting CBD-BDNF into the lateral
      ventricle of ICH rats. The results demonstrated that CBD-BDNF was retained at
      high levels in the hemorrhage hemisphere, where it promoted neural regeneration
      and angiogenesis, reduced tissue loss, and improved functional recovery. 

PMID- 24941994
TI  - Assessment of health-related quality of life in antiviral-treated Taiwanese
      chronic hepatitis C patients using SF-36 and CLDQ.
AB  - BACKGROUND: Interferon (IFN) therapy can cause significant side effects in
      chronic hepatitis C (CHC) patients; however, the health-related quality of life
      (HRQOL) of antiviral-treated CHC patients has not been established in Taiwan.
      This study evaluated domains and the degree to which antiviral treatment affects
      the HRQOL in CHC patients and identifies factors associated with variations
      between patients. METHODS: Health-related quality of life (HRQOL) was assessed
      using the Short Form-36 (SF-36) and the Chronic Liver Disease Questionnaire
      (CLDQ) in 108 antiviral-treated CHC patients. Eight scales and two summary scales
      of the SF-36 were compared with 256 age- and gender-matched population norms and
      64 age- and gender-matched CHC patients without antiviral therapy. Descriptive
      statistic measures, one-way ANOVA, and regression analysis were used for data
      analysis. RESULTS: (1) CHC patients receiving antiviral treatment displayed
      significantly lower scores in six scales, the Physical Component Summary (PCS),
      and the Mental Component Summary (MCS) of the SF-36, when compared to the
      population norms and patients without antiviral therapy (p < 0.05). (2) The mean
      CLDQ score of antiviral-treated patients was lower than that of patients without
      antiviral therapy, including subscales of 'fatigue', 'systemic symptoms', and
      'role emotion'. (3) All SF-36 subscales significantly correlated with all CLDQ
      subscales, with the greatest correlation coefficients shown between fatigue and
      vitality and mental health of SF-36. (4) Antiviral therapy had a greater negative
      impact on females in the CLDQ, on all patients during treatment weeks 9-16 in the
      PCS and on patients with a monthly income of less than NT$10,000 in the CLDQ,
      PCS, and MCS. CONCLUSIONS: This study highlighted impairments in the quality of
      life of chronic hepatitis C patients treated with IFN-based therapy. The
      significant factors associated with HRQOL include gender, income, and treatment
      duration. The results of this study might provide nurses with a comprehensive
      understanding of HRQOL and its determining factors in antiviral-treated CHC
      patients. The findings can serve as a useful reference for nursing personnel in
      developing instructions for upgrading the care of CHC patients.

PMID- 24941996
TI  - Interpreting measures of tuberculosis transmission: a case study on the
      Portuguese population.
AB  - BACKGROUND: Tuberculosis remains a high burden for Human society despite
      considerable investments in its control. Unique features in the history of
      infection and transmission dynamics of tuberculosis pose serious limitations on
      the direct interpretation of surveillance data and call for models that
      incorporate latent processes and simulate specific interventions. METHODS: A
      transmission model was adjusted to the dataset of active tuberculosis cases
      reported in Portugal between 2002 and 2009. We estimated key transmission
      parameters from the data (i.e. time to diagnosis, treatment length, default
      proportion, proportion of pulmonary TB cases). Using the adjusted model to the
      Portuguese case, we estimated the total burden of tuberculosis in Portugal. We
      further performed sensitivity analysis to heterogeneities in susceptibility to
      infection and exposure intensity. RESULTS: We calculated a mean time to diagnose
      of 2.81 months and treatment length of 8.80 months in Portugal. The proportion
      defaulting treatment was calculated as 0.04 and the proportion of pulmonary cases
      as 0.75. Using these values, we estimated a TB burden of 1.6 million infected
      persons, corresponding to more than 15% of the Portuguese population. We further
      described the sensitivity of these estimates to heterogeneity. CONCLUSIONS: We
      showed that the model reproduces well the observed dynamics of the Portuguese
      data, thus demonstrating its adequacy for devising control strategies for TB and
      predicting the effects of interventions.

PMID- 24941995
TI  - New population-based exome data question the pathogenicity of some genetic
      variants previously associated with Marfan syndrome.
AB  - BACKGROUND: Marfan syndrome (MFS) is a rare autosomal dominantly inherited
      connective tissue disorder with an estimated prevalence of 1:5,000. More than
      1000 variants have been previously reported to be associated with MFS. However,
      the disease-causing effect of these variants may be questionable as many of the
      original studies used low number of controls. To study whether there are possible
      false-positive variants associated with MFS, four in silico prediction tools
      (SIFT, Polyphen-2, Grantham score, and conservation across species) were used to
      predict the pathogenicity of these variant. RESULTS: Twenty-three out of 891
      previously MFS-associated variants were identified in the ESP. These variants
      were distributed on 100 heterozygote carriers in 6494 screened individuals. This
      corresponds to a genotype prevalence of 1:65 for MFS. Using a more conservative
      approach (cutoff value of >2 carriers in the EPS), 10 variants affected a total
      of 82 individuals. This gives a genotype prevalence of 1:79 (82:6494) in the ESP.
      A significantly higher frequency of MFS-associated variants not present in the
      ESP were predicted to be pathogenic with the agreement of >=3 prediction tools,
      compared to the variants present in the ESP (p = 3.5 * 10-15). CONCLUSIONS: This
      study showed a higher genotype prevalence of MFS than expected from the phenotype
      prevalence in the general population. The high genotype prevalence suggests that
      these variants are not the monogenic cause of MFS. Therefore, caution should be
      taken with regard to disease stratification based on these previously reported
      MFS-associated variants.

PMID- 24941997
TI  - Contrasting effects of preexisting hyperglycemia and higher body size on hospital
      mortality in critically ill patients: a prospective cohort study.
AB  - BACKGROUND: Obesity and diabetes mellitus are well-defined risk factors for
      cardiovascular mortality. The impact of antecedent hyperglycemia and body size on
      mortality in critical ill patients in intensive care units (ICUs) may vary across
      their range of values. Therefore, we prospectively analyzed the relationship
      between in-hospital mortality and preexisting hyperglycemia and body size in
      critically ill ICU patients to understand how mortality varied among normal,
      overweight, and obese patients and those with low, intermediate, and high
      glycated hemoglobin (HbA1c) levels. METHODS: Medical history, weight, height,
      physiologic variables, and HbA1c were obtained during the first 24 h for patients
      who were consecutively admitted to the high complexity ICU of Hospital de
      Clinicas de Porto Alegre, Brazil, from April to August 2011. The relationships
      between mortality and obesity and antecedent hyperglycemia were prospectively
      analyzed by cubic spline analysis and a Cox proportional hazards model. RESULTS:
      The study comprised 199 patients. The overall hospital mortality rate was 43.2%
      during a median 16 (8-28) days of follow-up. There was a progressive risk of in
      hospital mortality with higher HbA1c levels, with the relationship becoming
      significant at HbA1c >9.3% compared with lower levels (hazard ratio 1.74; 95%
      confidence interval with Bonferroni correction 1.49-2.80). In contrast, mean body
      mass index (BMI) was higher in survivors than in nonsurvivors (27.2 kg/m2 +/- 7.3
      vs. 24.7 kg/m2 +/- 5.0 P = 0.031, respectively). Cubic spline analysis showed
      that these relationships differed nonlinearly through the spectrum of BMI values.
      In a Cox proportional hazards model adjusted for Acute Physiology and Chronic
      Health Evaluation II score and HbA1c, the risk of in-hospital mortality
      progressively decreased with increasing BMI (BMI <20 vs. 20-23.9 kg/m2, P =
      0.032; BMI <20 vs. 24-34.9 kg/m2, P = 0.010; BMI <20 vs. >=35 kg/m2, P = 0.032).
      CONCLUSIONS: Our findings suggest that significant hyperglycemia prior to ICU
      admission is a risk factor for in-hospital mortality. Conversely, increasing BMI
      may confer an advantageous effect against mortality in critical illness
      independently of previous glycemic control.

PMID- 24941998
TI  - Morphological and physiological divergences within Quercus ilex support the
      existence of different ecotypes depending on climatic dryness.
AB  - BACKGROUND AND AIMS: Several studies show apparently contradictory findings about
      the functional convergence within the Mediterranean woody flora. In this context,
      this study evaluates the variability of functional traits within holm oak
      (Quercus ilex) to elucidate whether provenances corresponding to different
      morphotypes represent different ecotypes locally adapted to the prevaling stress
      levels. METHODS: Several morphological and physiological traits were measured at
      leaf and shoot levels in 9-year-old seedlings of seven Q. ilex provenances
      including all recognized morphotypes. Plants were grown in a common garden for 9
      years under the same environmental conditions to avoid possible biases due to
      site-specific characteristics. KEY RESULTS: Leaf morphometry clearly separates
      holm oak provenances into 'ilex' (more elongated leaves with low vein density)
      and 'rotundifolia' (short and rounded leaves with high vein density) morphotypes.
      Moreover, these morphotypes represent two consistent and very contrasting
      functional types in response to dry climates, mainly in terms of leaf area, major
      vein density, leaf specific conductivity, resistance to drought-induced
      cavitation and turgor loss point. CONCLUSIONS: The 'ilex' and 'rotundifolia'
      morphotypes correspond to different ecotypes as inferred from their contrasting
      functional traits. To the best of our knowledge, this is the first time that the
      combined use of morphological and physiological traits has provided support for
      the concept of these two holm oak morphotypes being regarded as two different
      species.

PMID- 24941999
TI  - Changes in tracheid and ray traits in fire scars of North American conifers and
      their ecophysiological implications.
AB  - BACKGROUND AND AIMS: Fire scars have been widely used as proxies for the
      reconstruction of fire history; however, little is known about the impact of fire
      injury on wood anatomy. This study investigates changes in tracheid and ray
      traits in fire scars of Douglas fir (Pseudotsuga menziesii), western larch (Larix
      occidentalis) and ponderosa pine (Pinus ponderosa), and discusses their
      ecophysiological implications for tree recovery from fire. METHODS: Transverse
      and tangential microsections were prepared for light microscopy and image
      analysis. Measurements of tracheids and rays were made in the three spatial
      dimensions: axially (at different section heights), radially (in different rings)
      and tangentially (with increasing distance from the wound margin). KEY RESULTS:
      Changes were strongest in the first year after fire injury, with a decrease in
      tracheid size (by 25-30 %) and an increase in tracheid density (by 21-53 %) for
      the three species. In addition, an increase in ray size (by 5-27 %) and an
      increase in ray density (by 19-36 %) were found in P. menziesii and L.
      occidentalis. Changes were comparable along the fire-injured stem and were often
      most marked close to the fire scar. CONCLUSIONS: The differentiation after fire
      injury of narrower and more numerous tracheids expresses a trade-off between
      hydraulic safety and hydraulic efficiency, while that of larger and more numerous
      rays serves compartmentalization and wound closure, mechanical strength and
      defence responses. Pinus ponderosa does not generally produce more ray tissue
      after fire injury and thus appears to be more adapted to fire.

PMID- 24942000
TI  - Variable response of three Trifolium repens ecotypes to soil flooding by
      seawater.
AB  - BACKGROUND AND AIMS: Despite concerns about the impact of rising sea levels and
      storm surge events on coastal ecosystems, there is remarkably little information
      on the response of terrestrial coastal plant species to seawater inundation. The
      aim of this study was to elucidate responses of a glycophyte (white clover,
      Trifolium repens) to short-duration soil flooding by seawater and recovery
      following leaching of salts. METHODS: Using plants cultivated from parent
      ecotypes collected from a natural soil salinity gradient, the impact of short
      duration seawater soil flooding (8 or 24 h) on short-term changes in leaf salt
      ion and organic solute concentrations was examined, together with longer term
      impacts on plant growth (stolon elongation) and flowering. KEY RESULTS: There was
      substantial Cl(-) and Na(+) accumulation in leaves, especially for plants
      subjected to 24 h soil flooding with seawater, but no consistent variation linked
      to parent plant provenance. Proline and sucrose concentrations also increased in
      plants following seawater flooding of the soil. Plant growth and flowering were
      reduced by longer soil immersion times (seawater flooding followed by drainage
      and freshwater inputs), but plants originating from more saline soil responded
      less negatively than those from lower salinity soil. CONCLUSIONS: The
      accumulation of proline and sucrose indicates a potential for solute accumulation
      as a response to the osmotic imbalance caused by salt ions, while variation in
      growth and flowering responses between ecotypes points to a natural adaptive
      capacity for tolerance of short-duration seawater soil flooding in T. repens.
      Consequently, it is suggested that selection for tolerant ecotypes is possible
      should the predicted increase in frequency of storm surge flooding events occur.

PMID- 24942001
TI  - Holoparasitic Rafflesiaceae possess the most reduced endophytes and yet give rise
      to the world's largest flowers.
AB  - BACKGROUND AND AIMS: Species in the holoparasitic plant family Rafflesiaceae
      exhibit one of the most highly modified vegetative bodies in flowering plants.
      Apart from the flower shoot and associated bracts, the parasite is a mycelium
      like endophyte living inside their grapevine hosts. This study provides a
      comprehensive treatment of the endophytic vegetative body for all three genera of
      Rafflesiaceae (Rafflesia, Rhizanthes and Sapria), and reports on the cytology and
      development of the endophyte, including its structural connection to the host,
      shedding light on the poorly understood nature of this symbiosis. METHODS: Serial
      sectioning and staining with non-specific dyes, periodic-Schiff's reagent and
      aniline blue were employed in order to characterize the structure of the
      endophyte across a phylogenetically diverse sampling. KEY RESULTS: A previously
      identified difference in the nuclear size between Rafflesiaceae endophytes and
      their hosts was used to investigate the morphology and development of the
      endophytic body. The endophytes generally comprise uniseriate filaments oriented
      radially within the host root. The emergence of the parasite from the host during
      floral development is arrested in some cases by an apparent host response, but
      otherwise vegetative growth does not appear to elicit suppression by the host.
      CONCLUSIONS: Rafflesiaceae produce greatly reduced and modified vegetative bodies
      even when compared with the other holoparasitic angiosperms once grouped with
      Rafflesiaceae, which possess some vegetative differentiation. Based on previous
      studies of seeds together with these findings, it is concluded that the endophyte
      probably develops directly from a proembryo, and not from an embryo proper.
      Similarly, the flowering shoot arises directly from the undifferentiated
      endophyte. These filaments produce a protocorm in which a shoot apex originates
      endogenously by formation of a secondary morphological surface. This degree of
      modification to the vegetative body is exceptional within angiosperms and
      warrants additional investigation. Furthermore, the study highlights a mechanical
      isolation mechanism by which the host may defend itself from the parasite.

PMID- 24942002
TI  - Patch size and distance: modelling habitat structure from the perspective of
      clonal growth.
AB  - BACKGROUND AND AIMS: This study considers the spatial structure of patchy
      habitats from the perspective of plants that forage for resources by clonal
      growth. Modelling is used in order to compare two basic strategies, which differ
      in the response of the plant to a patch boundary. The 'avoiding plant' (A) never
      grows out of a good (resource-rich) patch into a bad (resource-poor) region,
      because the parent ramet withdraws its subsidy from the offspring. The 'entering
      plant' (E) always crosses the boundary, as the offspring is subsidized at the
      expense of the parent. In addition to these two extreme scenarios, an
      intermediate mixed strategy (M) will also be tested. The model is used to compare
      the efficiency of foraging in various habitats in which the proportion of
      resource-rich areas (p) is varied. METHODS: A stochastic cellular automata (CA)
      model is developed in which habitat space is represented by a honeycomb lattice.
      Each cell within the lattice can accommodate a single ramet, and colonization can
      occur from a parent ramet's cell into six neighbouring cells. The CA consists of
      two layers: the population layer and the habitat. In the population layer, a cell
      can be empty or occupied by a ramet; in the habitat layer, a cell can be good
      (resource-rich) or bad (resource-poor). The habitat layer is constant; the
      population layer changes over time, according to the birth and death of ramets.
      KEY RESULTS: Strategies M and E are primarily limited by patch distance, whereas
      A is more sensitive to patch size. At a critical threshold of the proportion of
      resource-rich areas, p = 0.5, the mean patch size increases abruptly. Below the
      threshold, E is more efficient than A, whilst above the threshold the opposite is
      true. The mixed strategy (M) is more efficient than either of the pure strategies
      across a broad range of p values. CONCLUSIONS: The model predicts more
      species/genotypes with the 'entering' strategy, E, in habitats where resource
      rich patches are scattered, and more plants with the 'avoiding' strategy, A, in
      habitats where the connectivity of resource-rich patches is high. The results
      suggest that the degree of physiological integration between a parent and an
      offspring ramet is important even across a very short distance because it can
      strongly influence the efficiency of foraging.

PMID- 24942003
TI  - X-ray microtomography (micro-CT): a reference technology for high-resolution
      quantification of xylem embolism in trees.
AB  - As current methods for measuring xylem embolism in trees are indirect and prone
      to artefacts, there is an ongoing controversy over the capacity of trees to
      resist or recover from embolism. The debate will not end until we get direct
      visualization of the vessel content. Here, we propose desktop X-ray
      microtomography (micro-CT) as a reference direct technique to quantify xylem
      embolism and thus validate more widespread measurements based upon either
      hydraulic or acoustic methods. We used desktop micro-CT to measure embolism
      levels in dehydrated or centrifuged shoots of laurel - a long-vesseled species
      thought to display daily cycles of embolism formation and refilling. Our direct
      observations demonstrate that this Mediterranean species is highly resistant to
      embolism and is not vulnerable to drought-induced embolism in a normal range of
      xylem tensions. We therefore recommend that embolism studies in long-vesseled
      species should be validated by direct methods such as micro-CT to clear up any
      misunderstandings on their physiology. 

PMID- 24942004
TI  - Gastrointestinal Variant of Lemierre Syndrome: Fusobacterium nucleatum Bacteremia
      Associated Hepatic Vein Thrombosis: a Case Report and Literature Review.
AB  - Fusobacterium nucleatum is a gram-negative bacillius commonly found in oropharynx
      and is traditionally associated with Lemierre syndrome, which is characterized by
      history of recent oropharyngeal infection, internal jugular vein thrombosis, and
      isolation of anaerobic pathogens, mainly Fuosobacterium necrophorum. However,
      recent evidence indicated that F. nucleatum is also a normal resident of human
      gut. Less than a dozen of case reports had linked F. nucleatum to
      gastrointestinal variant of Lemierre syndrome with portal vein thrombosis.
      However, F. nucleatum bacteremia-associated hepatic vein thrombosis is very rare.
      We report a case of a 73-year-old man who had hepatic vein thrombosis associated
      with F. nucleatum bacteremia, most likely from subclinical primary infection
      affecting the lower gastrointestinal tract. The underlying pathophysiology and
      treatment options are discussed here. With rapid increase in reporting of
      Lemierre syndrome, this case deserves particular attention from clinicians. 

PMID- 24942005
TI  - Acyclovir-Induced Neurotoxicity: A Case Report and Review of Literature.
AB  - Neurotoxicity can develop as a side effect of intravenous acyclovir use in
      patients with renal impairment. It is underreported in clinical practice and
      often confused with worsening herpes encephalitis. We present a 69-year-old woman
      with end-stage renal disease on hemodialysis with acyclovir neurotoxicity treated
      with daily extended hemodialysis sessions. Daily hemodialysis for extended period
      may shorten the neurotoxicity period and can help with faster return to normal
      mentation. A high index of suspicion is warranted to diagnose acyclovir-induced
      neurotoxicity. 

PMID- 24942006
TI  - Efficacy and Safety of Prasugrel Compared With Clopidogrel for Patients With
      Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.
AB  - Dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor (clopidogrel,
      prasugrel, or ticagrelor) is essential to prevent thrombotic complications after
      percutaneous coronary intervention (PCI). The comparative efficacy between
      clopidogrel at a higher loading dose (600 mg) and prasugrel is uncertain. The aim
      of this study was to compare efficacy and safety of clopidogrel (higher loading
      dose) with prasugrel (loading dose of 60 mg) along with their respective
      maintenance doses in patients with acute coronary syndrome (ACS) undergoing PCI
      at 1 year. This is a retrospective, observational, pilot study. Patients with ACS
      who underwent PCI and received clopidogrel 600 mg or prasugrel 60 mg loading dose
      followed by maintenance doses of 75 mg and 10 mg, respectively, daily between
      July 1, 2009 and June 30, 2011 were enrolled. For patients who have died during
      the study period, investigators attempted to identify the cause of deaths through
      medical records or death certificates. Two hundred twenty-one patients were
      enrolled in the study. Primary efficacy end point, composite of death from
      cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke
      occurring through 1 year were not significantly different between the 2 treatment
      groups. Bleeding events were also not significant between the clopidogrel (N =
      136) and prasugrel (N = 85) groups: 9.6% versus 8.2%, P = 0.85. Prasugrel is at
      least as effective and safe as clopidogrel in patients with ACS undergoing early
      invasive management.

PMID- 24942007
TI  - The Effect of Coffee and Quantity of Consumption on Specific Cardiovascular and
      All-Cause Mortality: Coffee Consumption Does Not Affect Mortality.
AB  - Previous studies have examined whether or not an association exists between the
      consumption of caffeinated coffee to all-cause and cardiovascular mortality. This
      study aimed to delineate this association using population representative data
      from the National Health and Nutrition Examination Survey III. Patients were
      included in the study if all the following criteria were met: (1) follow-up
      mortality data were available, (2) age of at least 45 years, and (3) reported
      amount of average coffee consumption. A total of 8608 patients were included,
      with patients stratified into the following groups of average daily coffee
      consumption: (1) no coffee consumption, (2) less than 1 cup, (3) 1 cup a day, (4)
      2-3 cups, (5) 4-5 cups, (6) more than 6 cups a day. Odds ratios, 95% confidence
      intervals, and P values were calculated for univariate analysis to compare the
      prevalence of all-cause mortality, ischemia-related mortality, congestive heart
      failure-related mortality, and stroke-related mortality, using the no coffee
      consumption group as reference. These were then adjusted for confounding factors
      for a multivariate analysis. P < 0.05 were considered statistically significant.
      Univariate analysis demonstrated an association between coffee consumption and
      mortality, although this became insignificant on multivariate analysis. Coffee
      consumption, thus, does not seem to impact all-cause mortality or specific
      cardiovascular mortality. These findings do differ from those of recently
      published studies. Coffee consumption of any quantity seems to be safe without
      any increased mortality risk. There may be some protective effects but additional
      data are needed to further delineate this. 

PMID- 24942008
TI  - Posttreatment variables improve outcome prediction after intra-arterial therapy
      for acute ischemic stroke.
AB  - BACKGROUND: There are multiple clinical and radiographic factors that influence
      outcomes after endovascular reperfusion therapy (ERT) in acute ischemic stroke
      (AIS). We sought to derive and validate an outcome prediction score for AIS
      patients undergoing ERT based on readily available pretreatment and posttreatment
      factors. METHODS: The derivation cohort included 511 patients with anterior
      circulation AIS treated with ERT at 10 centers between September 2009 and July
      2011. The prospective validation cohort included 223 patients with anterior
      circulation AIS treated in the North American Solitaire Acute Stroke registry.
      Multivariable logistic regression identified predictors of good outcome (modified
      Rankin score <=2 at 3 months) in the derivation cohort; model beta coefficients
      were used to assign points and calculate a risk score. Discrimination was tested
      using C statistics with 95% confidence intervals (CIs) in the derivation and
      validation cohorts. Calibration was assessed using the Hosmer-Lemeshow test and
      plots of observed to expected outcomes. We assessed the net reclassification
      improvement for the derived score compared to the Totaled Health Risks in
      Vascular Events (THRIVE) score. Subgroup analysis in patients with pretreatment
      Alberta Stroke Program Early CT Score (ASPECTS) and posttreatment final infarct
      volume measurements was also performed to identify whether these radiographic
      predictors improved the model compared to simpler models. RESULTS: Good outcome
      was noted in 186 (36.4%) and 100 patients (44.8%) in the derivation and
      validation cohorts, respectively. Combining readily available pretreatment and
      posttreatment variables, we created a score (acronym: SNARL) based on the
      following parameters: symptomatic hemorrhage [2 points: none, hemorrhagic
      infarction (HI)1-2 or parenchymal hematoma (PH) type 1; 0 points: PH2], baseline
      National Institutes of Health Stroke Scale score (3 points: 0-10; 1 point: 11-20;
      0 points: >20), age (2 points: <60 years; 1 point: 60-79 years; 0 points: >79
      years), reperfusion (3 points: Thrombolysis In Cerebral Ischemia score 2b or 3)
      and location of clot (1 point: M2; 0 points: M1 or internal carotid artery). The
      SNARL score demonstrated good discrimination in the derivation (C statistic 0.79,
      95% CI 0.75-0.83) and validation cohorts (C statistic 0.74, 95% CI 0.68-0.81) and
      was superior to the THRIVE score (derivation cohort: C statistic 0.65, 95% CI
      0.60-0.70; validation cohort: C-statistic 0.59, 95% CI 0.52-0.67; p < 0.01 in
      both cohorts) but was inferior to a score that included age, ASPECTS, reperfusion
      status and final infarct volume (C statistic 0.86, 95% CI 0.82-0.91; p = 0.04).
      Compared with the THRIVE score, the SNARL score resulted in a net
      reclassification improvement of 34.8%. CONCLUSIONS: Among AIS patients treated
      with ERT, pretreatment scores such as the THRIVE score provide only fair
      prognostic information. Inclusion of posttreatment variables such as reperfusion
      and symptomatic hemorrhage greatly influences outcome and results in improved
      outcome prediction.

PMID- 24942010
TI  - Changes in adrenoceptors and G-protein-coupled receptor kinase 2 in L-NAME
      induced hypertension compared to spontaneous hypertension in rats.
AB  - This work compares the expression of adrenoceptors (ARs) and G-protein-coupled
      receptor kinase (GRK) 2 (RT-PCR and immunoblotting) and functional responses in
      conductance (aorta) and resistance vessels (mesenteric resistance arteries; MRA)
      in two different models of rat hypertension: hypertension induced by chronic
      treatment with L-NAME (N(G)-nitro-L-arginine methyl-ester) (L-NAME-treated rats;
      LNHR), and genetically induced hypertension (spontaneously hypertensive rats;
      SHR). Changes found in the aorta, but not in the MRA, were: (1) a loss of
      contractile capacity, more evidently in alpha1-AR-mediated contraction, and an
      impairment of endothelium-dependent vasorelaxation, with both changes occurring
      independently of the hypertensive model; (2) a diminished sensitivity to alpha1
      AR-induced vasoconstriction along with increased beta2-AR-mediated vasodilation
      in LNHR, and (3) a lower expression of ARs and GRK2 in LNHR. The two latter
      changes are the opposite of those previously found in aortas of SHR. In the MRA
      of LNHR, a diminished sensitivity to isoprenaline, in parallel with a reduced
      expression of beta1-AR, was observed without changes in GRK2 expression. In the
      MRA of SHR, the increased GRK2 expression was not accompanied by significant
      changes in either beta-AR expression or the vasorelaxant potency of isoprenaline.
      The present results highlight that changes in AR function differ not only between
      vessels but also between hypertensive models. Moreover, they suggest that changes
      in GRK2 expression could contribute to regulating beta2-AR function in
      conductance vessels but not beta1-AR function in resistance vessels.

PMID- 24942009
TI  - Adipocytes arise from multiple lineages that are heterogeneously and dynamically
      distributed.
AB  - Adipose tissue development is poorly understood. Here we use a lineage-tracing
      strategy optimal for adipocytes to provide evidence that Myf5 precursors are not
      the exclusive source of brown adipocytes and contribute more to the mature white
      and brite adipocyte populations than previously thought. Moreover, Myf5-lineage
      distribution in adipose tissue changes in response to modifiable and non
      modifiable factors. We also find that the Pax3 lineage largely overlaps with the
      Myf5 lineage in brown fat and subcutaneous white fat, but exhibits gender-linked
      divergence in visceral white fat while the MyoD1 lineage does not give rise to
      any adipocytes. Finally, by deleting insulin receptor beta in the Myf5 lineage,
      we provide in vivo evidence that the insulin receptor is essential for
      adipogenesis and that adipocyte lineages have plasticity. These data establish a
      conceptual framework for adipose tissue development and could explain body fat
      patterning variations in healthy and lipodystrophic or obese humans. 

PMID- 24942012
TI  - Temporal evolution of strut light intensity after implantation of bioresorbable
      polymeric intracoronary scaffolds in the ABSORB cohort B trial-an application of
      a new quantitative method based on optical coherence tomography.
AB  - BACKGROUND: Quantitative light intensity analysis of the strut core by optical
      coherence tomography (OCT) may enable assessment of changes in the light
      reflectivity of the bioresorbable polymeric scaffold from polymer to provisional
      matrix and connective tissues, with full disappearance and integration of the
      scaffold into the vessel wall. The aim of this report was to describe the
      methodology and to apply it to serial human OCT images post procedure and at 6,
      12, 24 and 36 months in the ABSORB cohort B trial. METHODS AND RESULTS: In serial
      frequency-domain OCT pullbacks, corresponding struts at different time points
      were identified by 3-dimensional foldout view. The peak and median values of
      light intensity were measured in the strut core by dedicated software. A total of
      303 corresponding struts were serially analyzed at 3 time points. In the
      sequential analysis, peak light intensity increased gradually in the first 24
      months after implantation and reached a plateau (relative difference with respect
      to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36
      months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at
      12 months, 75.0% at 24 months, 93.1% at 36 months). CONCLUSIONS: Quantitative
      light intensity analysis by OCT was capable of detecting subtle changes in the
      bioresorbable strut appearance over time, and could be used to monitor the
      bioresorption and integration process of polylactide struts.

PMID- 24942011
TI  - Vascular endothelial growth factor and its soluble receptors-1 and -2 in iris
      neovascularization and neovascular glaucoma.
AB  - Concentrations of vascular endothelial growth factor (VEGF), soluble VEGF
      receptor-1 (sVEGFR-1) and soluble VEGF receptor-2 (sVEGFR-2) were measured by
      enzyme-linked immunosorbent assay in 27 proliferative diabetic retinopathy
      patients who had iris neovascularization (INV) with or without neovascular
      glaucoma (NVG). The 27 eyes were divided into two groups, consisting of INV
      without elevation of the intraocular pressure (IOP; INV group) and INV with
      elevated IOP (NVG group). Ten patients with an idiopathic macular hole were used
      as the controls. The vitreous levels of VEGF, sVEGFR-1 and sVEGFR-2 showed a
      significant increase across the three groups. In the INV and NVG groups, the
      vitreous level of VEGF showed a significant correlation with the levels of sVEGFR
      1 and sVEGFR-2. There was also a significant correlation between the vitreous
      levels of sVEGFR-1 and sVEGFR-2. These results suggest that the vitreous levels
      of sVEGFR-1 and sVEGFR-2 are dependent on VEGF in patients who have INV with or
      without NVG.

PMID- 24942013
TI  - Premature ovarian insufficiency and neurological function.
AB  - Premature ovarian insufficiency (POI) involves loss of ovarian function before
      age 40. POI has been associated with neurological dysfunction and an increased
      risk of dementia, perhaps due to depletion in estrogen levels. The present review
      discusses the effects of POI caused by genetic disorder, natural premature
      menopause, surgical menopause, breast cancer treatment and gonadotropin-releasing
      hormone (GnRH) agonist treatment. Overall, data suggest an increased risk of
      neurological disorder where POI is due to premature menopause or induced from
      surgery. This increased risk appears to be most apparent on domains of global
      cognitive and verbal memory tests. Where POI is caused by genetic disorder,
      observed cognitive deficiencies may be more likely to have a genetic basis rather
      than being due to the effects of sex steroids on the brain. Findings related to
      loss of cognitive function after chemotherapy or GnRH treatments are mixed. There
      are also discrepant data related to use of hormone therapy after POI
      (particularly after surgical menopause). After surgery, hormone treatment appears
      to be most beneficial if initiated close to the average natural age of menopause.

PMID- 24942014
TI  - Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory
      acidosis: pathophysiological and technical considerations.
AB  - INTRODUCTION: While non-invasive ventilation aimed at avoiding intubation has
      become the modality of choice to treat mild to moderate acute respiratory
      acidosis, many severely acidotic patients (pH <7.20) still need intubation.
      Extracorporeal veno-venous CO2 removal (ECCO2R) could prove to be an alternative.
      The present animal study tested in a systematic fashion technical requirements
      for successful ECCO2R in terms of cannula size, blood and sweep gas flow.
      METHODS: ECCO2R with a 0.98 m(2) surface oxygenator was performed in six acidotic
      (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep
      gas flow rates of 8 and 16 L/minute, respectively. During each experiment the
      blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr
      catheter) and 1000 mL/minute (19Fr catheter). RESULTS: Amelioration of severe
      respiratory acidosis was only feasible when blood flow rates of 750 to 1000
      mL/minute (19Fr catheter) were used. Maximal CO2-elimination was 146.1 +/- 22.6
      mL/minute, while pH increased from 7.13 +/- 0.08 to 7.41 +/- 0.07 (blood flow of
      1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8
      L/minute resulted in a maximal CO2-elimination rate of 138.0 +/- 16.9 mL/minute.
      The 14.5Fr catheter allowed a maximum CO2 elimination rate of 77.9 mL/minute,
      which did not result in the normalization of pH. CONCLUSIONS: Veno-venous ECCO2R
      may serve as a treatment option for severe respiratory acidosis. In this porcine
      model, ECCO2R was most effective when using blood flow rates ranging between 750
      and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had
      less impact on ECCO2R in this setting.

PMID- 24942015
TI  - Congenital ADAMTS13 deficiency: a rare mimicker of immune thrombocytopenic
      purpura.
AB  - Congenital ADAMTS13 deficiency is a rare disease that leads to recurrent episodes
      of thrombotic thrombocytopenic purpura. We report a case that mimicked a
      recurring immune thrombocytopenic purpura in a child. Mild cases of ADAMTS13
      deficiency may be initially confused with immune thrombocytopenic purpura if
      hemolytic anemia is not severe and renal or neurological symptoms are not
      present. Fresh frozen plasma is the treatment of choice in acute thrombotic
      thrombocytopenic purpura in ADAMTS13-deficient patients. The best long-term
      treatment for slightly symptomatic cases remains to be elucidated. Recombinant
      human ADAMTS13 factor will be a promising option when commercially available. 

PMID- 24942016
TI  - Hyponatremia after desmopressin (DDAVP) use in pediatric patients with bleeding
      disorders undergoing surgeries.
AB  - Desmopressin (DDAVP) 1-deamino-8-D-arginine vasopressin is used in patients with
      bleeding disorders, including mild factor VIII deficiency, types 1 and 2 von
      Willebrand disease, and platelet function defects, undergoing surgeries to help
      control bleeding. We conducted a retrospective chart review of bleeding disorder
      patients undergoing inpatient surgery at Toledo Children's Hospital, OH, from
      2005 to 2009. Our study population included 107 patients aged 2 to 19 years with
      platelet function defects and von Willebrand disease. Our study aimed to evaluate
      the extent of hyponatremia caused by DDAVP and to propose a safe and effective
      treatment regimen for these patients. The mean change in sodium level before and
      after DDAVP was statistically significant within each age group. Thirteen
      patients had second dose of DDAVP withheld, and 11 patients had postoperative
      sodium levels <= 130 mEq/L. There were 2 patients with significant complications:
      a 6-year-old with postoperative bleeding and a 2-year-old with post-DDAVP tonic
      clonic seizures. We conclude that DDAVP causes significant hyponatremia, despite
      appropriate fluid restrictions. On the basis of our analysis, we recommend
      monitoring sodium levels before each dose of DDAVP and fluid restriction. These
      patients should be observed in the hospital setting after DDAVP administration
      for complications such as seizures and postoperative bleeding.

PMID- 24942017
TI  - Bone scintigraphy in osteosarcoma: a single institution experience.
AB  - Bone scintigraphy is a well-established method to evaluate for metastatic disease
      in osteosarcoma. We identified a patient who had a negative (cold) bone scan at
      skeletal relapse and consequently reviewed the frequency of cold scans in
      osteosarcoma at our institution. No cold scans were identified at diagnosis, and
      only 1 patient had a cold scan at skeletal recurrence. No correlation was
      identified between clinical outcomes and bone scan features, other than
      identification of metastatic disease. Patients with skeletal recurrence were all
      symptomatic, thus we suggest that bone scintigraphy is not indicated in routine
      postchemotherapy surveillance for patients with osteosarcoma. 

PMID- 24942018
TI  - Hemophilic Pseudotumor: An Important Differential Diagnosis of an Intracranial
      Mass.
AB  - Hemophilic pseudotumor is a rare complication of hemophilia. We present the case
      of a male toddler with moderate hemophilia A and cranial hemophilic pseudotumor
      managed with factor VIII infusions. We also provide a review of the literature.
      Recognition of this rare manifestation of this complication of hemophilia is
      important to provide correct treatment and avoid unnecessary investigations,
      particularly biopsy, which is contraindicated in this condition. 

PMID- 24942019
TI  - Clinically meaningful interpretation of pediatric health-related quality of life
      in sickle cell disease.
AB  - Health-related quality of life (HRQL) measures provide information about disease
      assessment; however, health care providers may be reluctant to use HRQL
      assessments as scores can be difficult to interpret. We sought to identify levels
      for impaired pain-related HRQL in children with sickle cell disease (SCD).
      Children (n=251) completed the Pediatric Quality of Life Inventory (PedsQL)
      Generic Core Scales and PedsQL SCD Module in a multisite study. Using children's
      item scores on the Pain and Hurt and Pain Impact scales of the PedsQL SCD Module,
      High, Intermediate, and Low Functioning groups were created. We compared
      functioning groups with the Pain and Hurt and Pain Impact scale scores to
      determine levels representing high and low HRQL. These scores were compared with
      disease severity and the PedsQL Generic Core Scales. Scores of <=60 on the PedsQL
      SCD Pain and Hurt and Pain Impact scales were associated with severe disease and
      met requirements for impaired functioning on the PedsQL Generic Core Scales.
      Scores of >=81 on the Pain and Hurt and the Pain Impact scales can be considered
      consistent with good HRQL in those domains in SCD. Alternately, scores of <=60
      are cause for concern and suggest areas of HRQL impairment in SCD. 

PMID- 24942020
TI  - Elevated tricuspid regurgitant velocity as a marker for pulmonary hypertension in
      children with sickle cell disease: less prevalent and predictive than previously
      thought?
AB  - Although elevated tricuspid regurgitant velocity (TRV), an echocardiographic
      marker for pulmonary hypertension, has previously been tied to mortality in adult
      patients with sickle cell disease, recent data demonstrated that it correlates
      poorly with catheterization findings. We describe the largest echocardiographic
      evaluation of pediatric patients with sickle cell disease to date, specifically
      the results of a protocol whereby a TRV>=250 cm/s prompted further evaluation. We
      investigated if elevated TRV would independently identify patients at risk for
      increased morbidity. A clinical echocardiographic database containing 630
      patients with sickle cell disease was retrospectively reviewed; 120 patients
      (19%) met inclusion criteria and were compared 1:1 to randomly selected age
      matched controls from the same database. By multivariate analysis, the elevated
      TRV cohort did not differ from controls in likelihood of acute chest episodes,
      hospitalization, or stroke. The study cohort's mean TRV in fact decreased to
      242+/-33 cm/s at follow-up without a discernible and comprehensive intervention
      to explain the improvement. Three patients had catheterization-proven pulmonary
      hypertension. In conclusion, elevated TRV in children with sickle cell disease is
      less prevalent than previously thought and is not independently associated with
      increased short-term morbidity. 

PMID- 24942021
TI  - Therapy-induced secondary acute myeloid leukemia with t(11;19)(q23;p13.1) in a
      pediatric patient with relapsed acute promyelocytic leukemia.
AB  - Acute myeloid leukemia is classified based upon recurrent cytogenetic
      abnormalities. The t(15;17)(q24.1;q21.1) abnormality is found in 5% to 8% of de
      novo acute myeloid leukemia and is diagnostic of acute promyelocytic leukemia
      (APL). The translocation results in fusion of the retinoic acid receptor-alpha
      (RARA) gene at 17q21.1 and the promyelocytic leukemia (PML) gene at 15q24.1.
      Standard APL therapy is a combination of all-trans retinoic acid and
      anthracycline-based chemotherapy. Anthracycline treatment is associated with
      secondary clonal chromosomal aberrations that can lead to therapy-related
      secondary myeloid neoplasms. We present a pediatric case of relapsed APL
      coexistent with treatment-associated secondary myeloid neoplasm with
      t(11;19)(q23;p13.1). 

PMID- 24942022
TI  - Phase I clinical trial of ifosfamide, oxaliplatin, and etoposide (IOE) in
      pediatric patients with refractory solid tumors.
AB  - Oxaliplatin, although related to cisplatin and carboplatin, has a more favorable
      toxicity profile and may offer advantages in combination regimens. We combined
      oxaliplatin, ifosfamide, and etoposide (IOE) and estimated the regimen's maximum
      tolerated dose (MTD) in children with refractory solid tumors. Dose-limiting
      toxicity (DLT) and MTD were assessed at 3 dose levels in a 21-day regimen: day 1,
      oxaliplatin 130 mg/m (consistent dose); days 1 to 3, ifosfamide 1200 mg/m/d
      (level 0) or 1500 mg/m/d (levels 1 and 2) and etoposide 75 mg/m/d (levels 0 and
      1) or 100 mg/m/d (level 2). Course 1 filgrastim/pegfilgrastim was permitted after
      initial DLT determination, if neutropenia was dose limiting. Seventeen patients
      received 59 courses. Without filgrastim (n=9), DLT was neutropenia in 2 patients
      at dose level 1. No DLT was observed after adding filgrastim (n=8). There was no
      ototoxicity, nephrotoxicity >grade 1, or neurotoxicity >grade 2. One patient
      experienced a partial response and 9 had stable disease after 2 courses. In
      conclusion, the IOE regimen was well tolerated. Without filgrastim, neutropenia
      was dose limiting with MTD at ifosfamide 1200 mg/m/d and etoposide 75 mg/m/d. The
      MTD with filgrastim was not defined due to early study closure. Filgrastim
      allowed ifosfamide and etoposide dose escalation and should be included in future
      studies.

PMID- 24942023
TI  - The biology of relapsed acute lymphoblastic leukemia: opportunities for
      therapeutic interventions.
AB  - Although great strides have been made in the improvement of outcome for newly
      diagnosed pediatric acute lymphoblastic leukemia because of refinements in risk
      stratification and selective intensification of therapy, the prognosis for
      relapsed leukemia has lagged behind significantly. Understanding the underlying
      biological pathways responsible for drug resistance is essential to develop novel
      approaches for the prevention of recurrence and treatment of relapsed disease.
      High throughput genomic technologies have the potential to revolutionize cancer
      care in this era of personalized medicine. Using such advanced technologies, we
      and others have shown that a diverse assortment of cooperative genetic and
      epigenetic events drive the resistant phenotype. Herein, we summarize results
      using a variety of genomic technologies to highlight the power of this
      methodology in providing insight into the biological mechanisms that impart
      resistant disease. 

PMID- 24942025
TI  - Massive splenic infarction and portal vein thrombosis in children with chronic
      myeloid leukemia.
AB  - Massive splenic infarction and portal vein thrombosis (PVT) due to chronic
      myeloid leukemia (CML) is extremely rare. We describe 2 children who were
      presented with massive splenic infarction and PVT in the course of CML. Massive
      splenic infarction and PVT treated with splenectomy in one and with medical
      treatment in another in whom PVT resolved by cytoreductive treatment, led to
      downsizing of spleen or splenectomy. Splenic infarct and PVT should be considered
      in CML patients with long-lasting severe abdominal pain despite appropriate
      medical attempts. Splenectomy should be spared for persistent symptoms and
      complications. 

PMID- 24942024
TI  - A significant proportion of thalassemia major patients have adrenal insufficiency
      detectable on provocative testing.
AB  - Advances in chelation therapy and noninvasive monitoring of iron overload have
      resulted in substantial improvements in the survival of transfusion-dependent
      patients with thalassemia major. Myocardial decompensation and sepsis remain the
      major causes of death. Although endocrine abnormalities are a well-recognized
      problem in these iron-overloaded patients, adrenal insufficiency and its
      consequences are underappreciated by the hematology community. The aims of this
      study were to determine the prevalence of adrenal insufficiency in thalassemia
      major subjects, to identify risk factors for adrenal insufficiency, and to
      localize the origin of the adrenal insufficiency within the hypothalamic
      pituitary-adrenal axis. Eighteen subjects with thalassemia major (18.9+/-9.3 y
      old, 7 female) were tested for adrenal insufficiency using a glucagon stimulation
      test. Those found to have adrenal insufficiency (stimulated cortisol <18 ug/dL)
      subsequently underwent an ovine corticotropin-releasing hormone (oCRH)
      stimulation test to define the physiological basis for the adrenal insufficiency.
      The prevalence of adrenal insufficiency was 61%, with an increased prevalence in
      males over females (92% vs. 29%, P=0.049). Ten of 11 subjects who failed the
      glucagon stimulation test subsequently demonstrated normal ACTH and cortisol
      responses to oCRH, indicating a possible hypothalamic origin to their adrenal
      insufficiency.

PMID- 24942026
TI  - Tumor Lysis Syndrome: An Unreported Complication of Intrathecal Ara-C.
AB  - Intrathecal (IT) chemotherapy is an established method of preventing and treating
      CNS leukemia. Although this intervention is beneficial and necessary,
      understanding the potential adverse effects of IT chemotherapy is important so
      that these potential effects can be anticipated and prevented. Tumor lysis
      syndrome is a known complication of systemic chemotherapy and has also been
      reported as a rare complication after IT chemotherapy in patients with CNS
      disease. We report the first case of tumor lysis syndrome occurring in a patient
      with T-cell acute lymphoblastic leukemia without CNS disease. The systemic
      effects of the IT chemotherapy were confirmed by the decreased size of the
      presenting mediastinal mass. 

PMID- 24942027
TI  - Diagnosis and Treatment of a Preterm Infant With Inoperable Congenital
      Hepatoblastoma--A Case Report.
AB  - Reports of hepatoblastoma (HB) in preterm infants are quite rare. Herein, we
      report the clinical management of a preterm infant with inoperable congenital HB.
      A female fetus that had been diagnosed with a large liver tumor consistent with
      hemangioma was delivered by emergency cesarean section at 33 weeks of gestation
      because of fetal distress. Effective antitumor therapy could not be performed,
      resulting in rapid deterioration and death. The postmortem histopathologic
      analysis confirmed the tumor as a HB. This report demonstrates the difficulties
      inherent in both the image diagnosis of HB and in providing efficacious
      treatments for preterm infants with HB. 

PMID- 24942028
TI  - Autoimmune neutropenia of infancy with recurrent urinary tract infections: a case
      report.
AB  - Autoimmune neutropenia of infancy is characterized by minor intercurrent
      infections despite severe neutropenia; severe bacterial infections are uncommon.
      An infant developed recurrent urinary tract infections at 9 and 11 months of age.
      The identified uropathogens were Escherichia coli and Enterococcus faecalis,
      respectively. Empirical treatment with carbapenems, as broad-spectrum
      antibiotics, promptly resolved the infection without sequelae. Febrile
      neutropenic children with cancer and autoimmune neutropenia can develop urinary
      tract infections; therefore, in such infants, urine culture should be obtained
      through catheterization. In febrile neutropenic infants with no apparent fever
      source, cephalosporin monotherapy should not be selected empirically because
      Enterococci can be the involved pathogens. 

PMID- 24942029
TI  - Complications of Reduced Intensity Conditioning HSCT for XIAP Deficiency
      (Alloimmune Cytopenias and HLH) Successfully Managed With Donor Lymphocyte
      Infusion.
AB  - X-linked inhibitor of apoptosis protein deficiency is a rare illness and although
      stem cell transplant is curative, full intensity conditioning is associated with
      high mortality rates. We describe a child with unusual complications associated
      with residual host lymphocytes following reduced intensity stem cell transplant.
      Recipient derived, donor directed, antigranulocyte antibodies led to life
      threatening and prolonged neutropenia and residual recipient lymphocytes
      reestablished hemophagocytic lymphohistiocytosis after withdrawal of immune
      suppression despite high levels of whole blood chimerism. Hemophagocytic
      lymphohistiocytosis was abolished following specific improvement in donor T-cell
      chimerism after donor lymphocyte infusions, and alloimmune cytopenias were no
      longer evident. 

PMID- 24942030
TI  - Does Teno Torque Virus Induce Autoimmunity After Hematopoietic Stem Cell
      Transplantation? A Case Report.
AB  - Teno Torque virus, member of the family of Anelloviridae, has been associated
      with many autoimmune diseases such as idiopathic hepatitis, systemic lupus
      erythematosus, and multiple sclerosis. Its viral load tends to be higher in the
      bone marrow and in tissues with high turnover rate. We report here a case of an
      11-month-old infant affected by acute myeloid leukemia who underwent
      hematopoietic stem cell transplantation, and after 6 months had autoimmune
      hepatitis and atopic dermatitis. Extremely high-cytokine IP-10 and eotaxin levels
      were found in her sera, and serological tests and RT-PCR for viruses showed
      positive results exclusively for Teno Torque virus. 

PMID- 24942031
TI  - An orbital mass. Ewing sarcoma.

PMID- 24942032
TI  - Childhood cancer in the cinema: how the celluloid mirror reflects psychosocial
      care.
AB  - OBJECTIVE: This study aims to evaluate the childhood cancer experience in
      commercially produced, readily available films that include a character with
      childhood cancer, with a particular focus on psychosocial care. METHODS: We
      reviewed 29 films, using quantitative and qualitative content analysis, to
      identify the medical and psychosocial characteristics of the cinematic childhood
      cancer experience. We rated psychosocial support on a 5-point scale (0 to 4)
      based on the availability and efficacy of support characters in the categories of
      nonprofessional internal (eg, parent), nonprofessional external (eg, friend),
      professional medical (eg, oncologist), and professional psychosocial (eg, social
      worker) supports. RESULTS: Film depicts an unrealistic, bleak picture of
      childhood cancer, with a 66% mortality rate among the 35 characters evaluated.
      Psychosocial supports portrayed in film are generally limited to resources
      already available to families before the cancer diagnosis: mean ratings across
      films were 2.4 for both nonprofessional, 1.6 for professional medical, and 0.3
      for professional psychosocial supports (Kruskal-Wallis chi3=43.1051, P<0.0001).
      Seven main themes emerged: disruption, social impact, psychological impact,
      physical toll, struggle/war/fight, coping, and barren landscape. Film generally
      depicts images of an isolated family courageously battling cancer alone with
      limited support from a treatment team solely dedicated to medical care.
      CONCLUSIONS: Commercially available films minimize the importance of the
      psychosocial dimension of care, which can perpetuate stigma around psychosocial
      needs and interventions. These films can be used to encourage discussion about
      how to optimize psychosocial care in pediatric oncology so that such care is not
      abandoned in actual practice as it is, for entertainment purposes, on the screen.

PMID- 24942033
TI  - Mucormycosis Rhinosinusitis at Diagnosis of Acute Lymphoblastic Leukemia:
      Diagnostics and Management Challenges in a Low-Middle-income Country.
AB  - We present the case of an adolescent with mucor rhinosinusitis diagnosed
      concomitantly with acute lymphoblastic leukemia at a hospital in Tegucigalpa,
      Honduras. We also discuss the challenges faced in the dual management of
      hematologic malignancies and invasive fungal disease in a low-middle-income
      country, such as access to diagnostics, immunosuppressants, imaging, and
      antifungals. Despite these shortcomings, the patient was successfully treated for
      both the diseases. Low-middle-income country hospitals can effectively treat
      invasive fungal diseases by providing adequate diagnostic and support services,
      which can improve the outcomes of pediatric cancer patients. 

PMID- 24942034
TI  - Meralgia Paresthetica as a Presentation of Acute Appendicitis in a Girl With
      Acute Lymphoblastic Leukemia.
AB  - A 7-year-old girl with Philadelphia chromosome-positive acute lymphoblastic
      leukemia developed recurrent fever and meralgia paresthetica (MP) during
      chemotherapy, which resolved after administration of antibiotics. Five months
      after the onset of these symptoms, enhanced computed tomography showed a
      periappendiceal abscess extending into the psoas muscle. The cause of her fever
      and MP was thought to be appendicitis, which probably developed during induction
      chemotherapy but did not result in typical abdominal pain. Patients with
      recurrent fever and MP should be evaluated by imaging examinations including
      computed tomography to search for appendicitis. 

PMID- 24942035
TI  - Langerhans cell sarcoma: case report and review of world literature.
AB  - Langerhans cell sarcoma is a rare malignancy with only 1 pediatric case (less
      than 15 y of age) reported. Here, we report the second case of Langerhans cell
      sarcoma in a child who presented with cord compression. This patient was treated
      with extensive surgical resection, postoperative chemotherapy, and involved-field
      radiation therapy. She completed therapy and remains in remission for 27 months.
      A review and analysis of all 53 cases published in the world literature is
      provided to help guide physicians treating this disease. Recently discovered
      genetic mutation involving BRAF is also discussed. 

PMID- 24942036
TI  - Pantoea agglomerans bacteremia in a child with acute lymphoblastic leukemia
      during induction therapy.

PMID- 24942039
TI  - Molecular epidemiology of OXA-48-producing Klebsiella pneumoniae in France.
AB  - We characterized 53 OXA-48-producing Klebsiella pneumoniae (OXA-48-Kp) isolated
      between 2011 and 2013 in 21 French hospitals. All the isolates were genotyped
      using MLST and PFGE and the population structure of the species was determined by
      a nucleotide-based analysis of the entire K. pneumoniae MLST database. Most of
      the OXA-48-Kp isolates also produced CTX-M-15 and remained susceptible to
      imipenem and meropenem. The isolates were distributed into 20 STs, of which five
      were dominant (ST15, ST101, ST147, ST395 and ST405). All the OXA-48-Kp clustered
      in the major clade of K. pneumoniae KpI. 

PMID- 24942040
TI  - Multi-taxa trait and functional responses to physical disturbance.
AB  - Examining assemblage trait responses to environmental stressors extends our
      understanding beyond patterns of taxonomic diversity and composition, with
      results potentially transferable among bioregions. But the degree to which trait
      responses may be generalized across taxonomic groups remains incompletely
      understood. We compared trait responses among carabids, spiders and plants to an
      experimentally manipulated gradient of physical disturbance, replicated in open
      habitats within a forested landscape. Recolonization of recently disturbed
      habitats is expected to favour species with traits that promote greater dispersal
      ability, independent of taxa. We specifically predicted that physical disturbance
      would increase the representation of carabids with smaller body size, wings or
      wing dimorphism, spiders able to disperse aerially, and plants with therophyte
      life-history and wind-dispersed seed. We sampled 197 arthropod species (14,738
      individuals) and 164 species of plant. The strength of association between each
      trait and the disturbance intensity was quantified by correlating matrices of
      species by traits, species abundance by sites and sites by environment, with
      significance assessed by comparison with a null model. Responses of biological
      traits varied among taxa but could be consistently interpreted in terms of
      dispersal ability. Trait shifts for carabid and plant assemblages were as
      predicted and correspond to those observed in other disturbance regimes.
      Assemblages after disturbance comprised smaller and winged carabids, and smaller
      plants with wind-dispersed seed, consistent with selection for species with
      better dispersal ability. In contrast, aerial dispersal did not appear important
      in spider recolonization, instead terrestrial dispersal ability was suggested by
      the increased abundance of larger-bodied and cursorial species. However, larger
      spider body size was also associated with an active-hunting strategy, also
      favoured in the post-disturbance environment. Trait-function linkage differed
      among taxa and was sometimes diffuse, with covariance among biological traits and
      the mapping of individual traits to multiple ecological functions. In particular,
      body size responses reflected correlations with life history, susceptibility to
      perturbation and dispersal ability that were inconsistent between the two
      arthropod groups. Selection of traits for assessment should therefore be taxa
      specific. Generalizations of trait responses across taxa should only be conducted
      where functional or ecological significance of assembly-level changes can be
      understood.

PMID- 24942041
TI  - Long-term use of occlusal appliance has impact on sleep structure.
AB  - Acrylic occlusal appliances (OAs) have been used for temporomandibular disorders
      and sleep bruxism, but the effects of the treatment are still insufficiently
      evaluated. Two all-night polysomnographic recordings were made in a sleep
      laboratory on 14 bruxists (9 females and 5 males with mean age of 27.5 years).
      The measurement included basic polysomnography with additional masseter muscle
      electromyogram and movement recording (static charge-sensitive bed method) using
      randomisation. The base night recording was followed by the second study night
      after 8 weeks regular use of OA. The OA was made on the occlusal surface of the
      teeth of the upper jaw, and it was used at night time during the study period.
      With the OA, rapid eye movement sleep changed from 23.3% to 19.6% (P = 0.078),
      and slow wave sleep increased significantly from 10.2% to 14.7% (P = 0.039).
      Masseter contraction (MC) episodes occurred with similar frequency (9.7 vs. 10.5
      episodes per hour, P = 0.272). The intensity of the rhythmic MC bursts within an
      episode decreased from 5.5 to 4.4 (P = 0.027). The groups were post hoc divided
      into responders and non-responders using a 20% change in MC episode per hour as a
      cut-off point. The results indicated that 43% of bruxists increased activity
      (negative responders), while 36% decreased (positive responders), and in 21%,
      there was no change in the level. It is concluded that OA does not have
      significant feedback inhibition on masseter muscle motor activity during sleep.
      However, OA may increase slow wave sleep.

PMID- 24942038
TI  - Parent support is less effective in buffering cortisol stress reactivity for
      adolescents compared to children.
AB  - The goal of the present study was to investigate developmental differences in the
      effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA)
      axis stress responses of children (ages 9-10, N = 40) and adolescents (ages 15
      16, N = 41). We experimentally manipulated the provision of parent support during
      the speech preparation period before a modified Trier Social Stress Test (TSST)
      and examined its effect on levels of salivary cortisol secreted in response to
      this laboratory stressor. Analyses revealed a significant interaction of
      condition and age group such that social support from the parent (versus a
      stranger) significantly eliminated the cortisol stress response in children, but
      had no effect on the response among adolescents. 

PMID- 24942042
TI  - Red blood cell storage increases hypoxia-induced nitric oxide bioavailability and
      methemoglobin formation in vitro and in vivo.
AB  - BACKGROUND: In this study we investigated whether storage of red blood cells
      (RBCs) leads to alterations in nitrite reductase activity, hence in altered
      hypoxia-induced nitric oxide (NO) bioavailability and methemoglobin formation.
      STUDY DESIGN AND METHODS: Hypoxia-induced NO bioavailability and methemoglobin
      formation were measured in vitro after nitrite administration to fresh (<1 week
      of storage) and aged (5-6 weeks of storage) human RBC units and in blood samples
      of hemodiluted rats subjected to hypoxic ventilation after transfusion with fresh
      or aged human RBCs. RESULTS: In vitro, NO and methemoglobin levels 10 minutes
      after nitrite administration were lower in the fresh RBC samples compared to the
      aged RBC samples (p = 0.026 and p = 0.022, respectively). In vivo, NO
      bioavailability was also significantly lower in the rats receiving fresh RBCs
      compared to the group receiving aged RBCs (p = 0.003). In line with NO
      bioavailability, methemoglobin levels were higher, albeit not significantly, in
      the group receiving aged RBCs compared to in the group receiving fresh RBCs (p =
      0.154). The difference in methemoglobin formation after nitrite administration
      between fresh and aged RBCs was only present under deoxygenated conditions and
      not under oxygenated conditions. There were no differences in methemoglobin
      reductase activity between fresh and aged RBCs. CONCLUSIONS: Storage of RBCs
      leads to an increased rate of hypoxia-induced nitrite reduction to NO and this is
      associated with increased methemoglobin formation. The increased methemoglobin
      formation and consequent decrease in oxygen delivery capacity might contribute to
      the storage-related impairment of aged RBCs to oxygenate the microcirculation.

PMID- 24942044
TI  - Seed metabolomic study reveals significant metabolite variations and correlations
      among different soybean cultivars.
AB  - Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean
      seeds are a rich and important resource for proteins and oils. While "omics"
      studies, such as genomics, transcriptomics, and proteomics, have been widely
      applied in soybean molecular research, fewer metabolomic studies have been
      conducted for large-scale detection of low molecular weight metabolites,
      especially in soybean seeds. In this study, we investigated the seed metabolomes
      of 29 common soybean cultivars through combined gas chromatography-mass
      spectrometry and ultra-performance liquid chromatography-tandem mass
      spectrometry. One hundred sixty-nine named metabolites were identified and
      subsequently used to construct a metabolic network of mature soybean seed. Among
      the 169 detected metabolites, 104 were found to be significantly variable in
      their levels across tested cultivars. Metabolite markers that could be used to
      distinguish genetically related soybean cultivars were also identified, and
      metabolite-metabolite correlation analysis revealed some significant associations
      within the same or among different metabolite groups. Findings from this work may
      potentially provide the basis for further studies on both soybean seed metabolism
      and metabolic engineering to improve soybean seed quality and yield. 

PMID- 24942043
TI  - Complement protein C1q and adiponectin stimulate Mer tyrosine kinase-dependent
      engulfment of apoptotic cells through a shared pathway.
AB  - The failure to clear apoptotic cells is linked to defects in development and
      autoimmunity. Complement component C1q is required for efficient engulfment of
      apoptotic cells (efferocytosis), and C1q deficiency leads to the development of
      lupus. We recently identified a novel molecular mechanism for C1q-dependent
      efferocytosis in murine macrophages. C1q elicited the expression of Mer tyrosine
      kinase (Mer), a receptor that regulates efficient efferocytosis and prevention of
      autoimmunity. To characterize the C1q-dependent signal transduction mechanism,
      pathway analysis of the transcriptome from C1q-activated macrophages was
      performed, and it identified the adiponectin signaling pathway as significantly
      upregulated with C1q. Adiponectin is structurally homologous to C1q and regulates
      cellular metabolism via downstream activation of 5'adenosine monophosphate
      activated protein kinase (AMPK). Macrophage stimulation with C1q resulted in the
      activation of AMPK, and silencing of AMPK expression using siRNA-inhibited C1q
      dependent efferocytosis. Adiponectin signaling also stimulates activation of
      nuclear receptors, and inhibition of the nuclear receptor retinoid X receptor
      abrogated C1q-dependent Mer expression and efferocytosis. Furthermore,
      adiponectin elicited Mer expression and Mer-dependent efferocytosis in
      macrophages similar to cells stimulated with C1q. Collectively, our results
      suggest that C1q and adiponectin share a common signal transduction cascade to
      promote clearance of apoptotic cells, and identify a novel molecular pathway
      required for efficient efferocytosis.

PMID- 24942046
TI  - Ultraviolet radiation exposure and serum vitamin D levels in young children.
AB  - AIM: Health benefits of adequate vitamin D levels in the blood include better
      bone health and a reduced incidence of a range of chronic diseases and
      infections. Ultraviolet (UV) radiation exposure from the sun is the main source
      of vitamin D; however, such exposure, especially from a young age, is also a
      potential risk factor for skin cancer. The current study examined the association
      of UV exposure with vitamin D production in young children to determine the
      period of weekly exposure prior to blood testing that affected serum 25
      hydroxyvitamin D (25(OH)D) levels. METHODS: Between 2009 and 2011, healthy
      children aged 3, 6 and 9 years were recruited from the community for a cross
      sectional study of nutritional factors and DNA damage. Parents of 464 children
      provided information on the children's average weekly sun exposure and level of
      sun protection during each of the 16 weeks before blood sample collection by a
      domiciliary phlebotomist. RESULTS: Serum 25(OH)D levels were best predicted from
      UV exposure during the week before blood collection for samples drawn in autumn,
      summer or spring. For samples drawn in winter, serum 25(OH)D levels were best
      predicted by UV exposure during the 2 weeks before blood collection. CONCLUSIONS:
      Consistent weekly sun exposure may be beneficial for young children, especially
      in winter, to maintain healthy vitamin D levels in the blood. However,
      confirmation of these results is needed before their public health significance
      can be fully evaluated.

PMID- 24942047
TI  - Youth alcohol polarization effects in regional but not national data.

PMID- 24942045
TI  - Brain signatures of moral sensitivity in adolescents with early social
      deprivation.
AB  - The present study examined neural responses associated with moral sensitivity in
      adolescents with a background of early social deprivation. Using high-density
      electroencephalography (hdEEG), brain activity was measured during an intentional
      inference task, which assesses rapid moral decision-making regarding intentional
      or unintentional harm to people and objects. We compared the responses to this
      task in a socially deprived group (DG) with that of a control group (CG). The
      event-related potentials (ERPs) results showed atypical early and late frontal
      cortical markers associated with attribution of intentionality during moral
      decision-making in DG (especially regarding intentional harm to people). The
      source space of the hdEEG showed reduced activity for DG compared with CG in the
      right prefrontal cortex, bilaterally in the ventromedial prefrontal cortex
      (vmPFC), and right insula. Moreover, the reduced response in vmPFC for DG was
      predicted by higher rates of externalizing problems. These findings demonstrate
      the importance of the social environment in early moral development, supporting a
      prefrontal maturation model of social deprivation. 

PMID- 24942048
TI  - Callosal alterations in pyridoxine-dependent epilepsy.
AB  - AIM: While there have been isolated reports of callosal morphology differences in
      pyridoxine-dependent epilepsy (PDE), a rare autosomal disorder caused by ALDH7A1
      gene mutations, no study has systematically evaluated callosal features in a
      large sample of patients. This study sought to overcome this knowledge gap.
      METHOD: Spanning a wide age range from birth to 48 years, corpus callosum
      morphology and cross-sectional cerebral area were measured in 30 individuals with
      PDE (12 males, 18 females, median age 3.92y; 25th centile 0.27, 75th centile
      15.25) compared to 30 age-matched comparison individuals (11 males, 19 females,
      median age 3.85y; 25th centile 0.26, 75th centile 16.00). Individuals with PDE
      were also divided into age groups to evaluate findings across development. As
      delay to treatment may modulate clinical severity, groups were stratified by
      treatment delay (less than or greater than 2wks from birth). RESULTS: Markedly
      reduced callosal area expressed as a ratio of mid-sagittal cerebral area was
      observed for the entire group with PDE (p<0.001). Stratifying by age (<1y, 1-10y,
      >10y) demonstrated posterior abnormalities to be a consistent feature, with
      anterior regions increasingly involved across the developmental trajectory.
      Splitting the PDE group by treatment lag did not reveal overall or sub-region
      callosal differences. INTERPRETATION: Callosal abnormalities are a common feature
      of PDE not explained by treatment lag. Future work utilizing tract-based
      approaches to understand inter- and intra-hemispheric connectivity patterns will
      help in the better understanding the structural aspects of this disease.

PMID- 24942049
TI  - Forced collapse of the blastocoel cavity improves developmental potential in
      cryopreserved bovine blastocysts by slow-rate freezing and vitrification.
AB  - This study was conducted to evaluate the effectiveness of forced collapse of the
      blastocoel before slow-rate freezing and vitrification of bovine blastocysts.
      Cryopreservation of bovine blastocysts has been proposed as a tool to improve the
      feasibility of cattle production using the embryo transfer technique. However,
      the low efficiency of frozen-thawed embryos survival and further development is a
      crucial problem. In this study, bovine in vitro and in vivo blastocysts were slow
      rate frozen and vitrified after forced blastocoele collapse (FBC) of the
      blastocyst cavity by puncturing the blastocoele with a pulled Pasteur pipet.
      Differences in the developmental potential of frozen-thawed blastocysts derived
      from FBC and non-FBC groups were found in both slow-rate freezing and
      vitrification. Furthermore, we found that the total cell number of blastocysts in
      FBC groups was increased and the index of apoptosis in FBC groups was decreased.
      Consistent with these results, real-time RT-PCR analysis data showed that
      expression of the anti-apoptotic Bcl-XL gene was significantly increased by FBC
      groups, whereas expression of the pro-apoptotic Bax gene was significantly
      decreased by FBC groups. Our results also showed that pregnancy outcomes in both
      slow-rate frozen and vitrified bovine in vivo blastocysts could be improved by
      reducing the fluid content after FBC of the blastocyst cavity. Therefore, we
      suggest that FBC of the blastocyst cavity with a pulled Pasteur pipet is an
      effective pre-treatment technique for both slow-rate freezing and vitrification
      of bovine blastocysts.

PMID- 24942050
TI  - Construct validity and test-retest reliability of the International Fitness Scale
      (IFIS) in Spanish children aged 9-12 years.
AB  - We aimed to examine (a) the construct validity and reliability of the
      International Fitness Scale (IFIS) in children; and (b) the association of both
      self-reported and measured fitness with cardiometabolic risk. Cross-sectional
      study in 1145 Spanish children (9-12 years). We measured body fat, waist
      circumference, blood pressure, lipids, insulin, and fitness level (reported and
      measured). A validated cardiometabolic syndrome index was used. An age- and sex
      matched sample of 245 children originally not included in the study sample
      fulfilled IFIS twice for reliability purposes. IFIS was able to correctly
      classify children according to their measured fitness levels (analysis of
      covariance, adjusted for sex and age was used). Test-retest reliability of IFIS
      items was also good, i.e., average weighted Kappa = 0.70. Our data also suggest
      that both measured and reported cardiorespiratory, and speed and agility fitness
      were associated with cardiometabolic risk factors, such as adiposity and a
      cardiometabolic syndrome risk score. The associations for muscular fitness (both
      reported and measured) differed depending on how it was expressed (i.e., absolute
      vs relative terms). Our findings suggest that self-reported fitness, as assessed
      by IFIS, is a valid, reliable, and health-related measure, and it can be a good
      alternative at population level when physical fitness cannot be measured. 

PMID- 24942051
TI  - Suppression among alleles encoding nucleotide-binding-leucine-rich repeat
      resistance proteins interferes with resistance in F1 hybrid and allele-pyramided
      wheat plants.
AB  - The development of high-yielding varieties with broad-spectrum durable disease
      resistance is the ultimate goal of crop breeding. In plants, immune receptors of
      the nucleotide-binding-leucine-rich repeat (NB-LRR) class mediate race-specific
      resistance against pathogen attack. When employed in agriculture this type of
      resistance is often rapidly overcome by newly adapted pathogen races. The
      stacking of different resistance genes or alleles in F1 hybrids or in pyramided
      lines is a promising strategy for achieving more durable resistance. Here, we
      identify a molecular mechanism which can negatively interfere with the allele
      pyramiding approach. We show that pairwise combinations of different alleles of
      the powdery mildew resistance gene Pm3 in F1 hybrids and stacked transgenic wheat
      lines can result in suppression of Pm3-based resistance. This effect is
      independent of the genetic background and solely dependent on the Pm3 alleles.
      Suppression occurs at the post-translational level, as levels of RNA and protein
      in the suppressed alleles are unaffected. Using a transient expression system in
      Nicotiana benthamiana, the LRR domain was identified as the domain conferring
      suppression. The results of this study suggest that the expression of closely
      related NB-LRR resistance genes or alleles in the same genotype can lead to
      dominant-negative interactions. These findings provide a molecular explanation
      for the frequently observed ineffectiveness of resistance genes introduced from
      the secondary gene pool into polyploid crop species and mark an important step in
      overcoming this limitation. 

PMID- 24942052
TI  - Zinc in the biosciences.

PMID- 24942053
TI  - Multiplanar breast kinematics during different exercise modalities.
AB  - Multiplanar breast movement reduction is crucial to increasing physical activity
      participation amongst women. To date, research has focused on breast movement
      during running, but until breast movement is understood during different exercise
      modalities, the breast support requirements for specific activities are unknown.
      To understand breast support requirements during different exercise modalities,
      this study aimed to determine multiplanar breast kinematics during running,
      jumping and agility tasks. Sixteen 32D participants had markers attached to their
      right nipple and torso. Relative multiplanar breast displacement was calculated
      during bare-breasted treadmill running (10 kph), maximum countermovement jumping
      and an agility t-test. Exercise modality influenced the magnitude and direction
      of breast displacement, velocity and acceleration (p < .05). Jumping produced
      greater vertical breast displacement (.09 m) but less mediolateral breast
      displacement (.05 m) than running or the agility task, but agility tasks produced
      the highest multiplanar breast velocities and acceleration. Breast movement
      during jumping was predominantly in the vertical direction, whereas the agility
      task produced a greater percentage of mediolateral breast acceleration than
      running or jumping. Exercise modality impacted upon the magnitude and
      distribution of bare-breasted multiplanar breast kinematics in this homogenous
      32D cohort. Therefore, to reduce breast movement in women of a 32D bra size,
      manufacturers may wish to design sport-specific products, with greater vertical
      support for exercise modalities incorporating jumping and greater mediolateral
      support for agility tasks.

PMID- 24942054
TI  - A new theoretical framework for modeling respiratory protection based on the beta
      distribution.
AB  - The problem of modeling respiratory protection is well known and has been dealt
      with extensively in the literature. Often the efficiency of respiratory
      protection is quantified in terms of penetration, defined as the proportion of an
      ambient contaminant concentration that penetrates the respiratory protection
      equipment. Typically, the penetration modeling framework in the literature is
      based on the assumption that penetration measurements follow the lognormal
      distribution. However, the analysis in this study leads to the conclusion that
      the lognormal assumption is not always valid, making it less adequate for
      analyzing respiratory protection measurements. This work presents a formulation
      of the problem from first principles, leading to a stochastic differential
      equation whose solution is the probability density function of the beta
      distribution. The data of respiratory protection experiments were reexamined, and
      indeed the beta distribution was found to provide the data a better fit than the
      lognormal. We conclude with a suggestion for a new theoretical framework for
      modeling respiratory protection. 

PMID- 24942055
TI  - A randomized, controlled, clinical pilot study assessing the analgesic effect of
      morphine applied topically onto split-thickness skin wounds.
AB  - OBJECTIVES: To assess the effect of an opioid administered topically onto a
      standardized skin wound in patients without significant comorbidity. Findings to
      date are contradictory, often obtained from multimorbid patients with wounds
      lacking uniformity. METHODS: Forty-four patients undergoing surgery for skin
      grafting were randomly assigned to receive morphine (0.25, 0.75 or 1.25 mg/100
      cm(2) wound size) in hydroxyethylcellulose gel or placebo applied onto the
      excised split-thickness donor wound at the end of surgery. Pain, supplementary
      systemic opioids and adverse effects were assessed during the first 24 h after
      application. Healing was examined when the dressings were removed. KEY FINDINGS:
      Morphine doses ranged from 0.25 to 5.4 mg (mean 1.93 +/- standard deviation 1.34
      mg). No differences in pain scores or use of supplementary analgesics were found
      between the groups. Serious adverse effects did not occur; healing was not
      impaired. Large intragroup variability was observed for pain scores, wound sizes
      and supplementary analgesia. CONCLUSIONS: Patients treated with topically applied
      morphine gel onto standardized skin wounds did not report lower pain scores
      compared with placebo-treated patients. Larger groups would be required to arrive
      at definitive conclusions. The split-thickness skin graft model can be used for
      future research.

PMID- 24942056
TI  - Experiences of undergraduate African health sciences students: A hermeneutic
      inquiry.
AB  - While efforts have been made to understand the experiences of African students in
      predominantly white environments, the experiences of African students in clinical
      placement areas have rarely been explored. This paper is a report on a study
      designed to address the gap in educational research on the experiences of African
      health sciences students in clinical placements in predominantly white
      environments. Interviews adopting an open approach to conversations were
      conducted with nine African students from three health disciplines at one
      metropolitan university in Australia between 2012 and 2013. Interview transcripts
      were analyzed using philosophical hermeneutics, where shared meanings were
      arrived at by employing key Gadamerian hermeneutic components. Findings revealed
      a number of factors that had a direct effect on the meaning students derived from
      their clinical placement experiences. These, as revealed in the interlinked
      domains of body, space, relationships, and time included difference, acceptance,
      resilience, and cultural sensitivity. Insights from this study may lead to the
      adoption of strategies designed to improve the experiences of African students
      studying health sciences in predominantly white environments. 

PMID- 24942057
TI  - A new cyclopeptide metabolite of marine gut fungus from Ligia oceanica.
AB  - A new cyclopeptide, together with three known amino acid derivatives, was
      isolated from marine-derived fungus Aspergillus flavipes, which was found in the
      gut of isopod Ligia oceanica. The novel peptide contains four amino acid units,
      proline, 5-methoxyanthranilic acid, isoleucine and 3-aminoacrylic acid. Its
      structure was determined on the basis of NMR, HR-MS and MS(n) spectral data
      analysis. The two unusual amino acid residues, 5-methoxyanthranilic acid and 3
      aminoacrylic acid, were first found in natural product. The known compound N
      benzoyl-phenylalanine methyl ester was first found as fungal metabolite. This is
      the first report of natural products isolated from marine gut fungi. 

PMID- 24942059
TI  - The need to determine whether lung metastasectomy improves survival in advanced
      colorectal cancer.

PMID- 24942058
TI  - Effect of superstimulation protocols on nuclear maturation and distribution of
      lipid droplets in bovine oocytes.
AB  - Our objective was to study the effect of superstimulation protocols on nuclear
      maturation of the oocyte and the distribution of lipid droplets in the ooplasm.
      Heifers (n=4 each group) during the luteal phase were either treated with FSH for
      4 days (Short FSH), FSH for 4 days followed by 84h of gonadotropin free period
      (FSH Starvation) or for 7 days (Long FSH) starting from the day of wave
      emergence. In all groups, LH was given 24h after induced luteolysis (penultimate
      day of FSH) and cumulus-oocyte complexes were collected 24h later. Oocytes were
      stained for nuclear maturation (Lamin/chromatin) and lipid droplets (Nile red).
      The Long FSH group had a greater proportion of mature oocytes (metaphase II)
      compared with heifers in the Short FSH and FSH Starvation groups (59/100 vs 5/23
      and 2/25, respectively; P<0.01). On average across all groups, oocytes contained
      22pL of lipids (3.3% of ooplasm volume) distributed as 3000 droplets. Average
      volume of individual lipid droplets was higher in the FSH Starvation (11.5+/-1.5
      10(-3) pL, P=0.03) compared with the Short and Long FSH groups (7.2+/-0.6 10(-3)
      and 8.0+/-0.8 10(-3) pL, respectively). In conclusion, both FSH Starvation and
      Short FSH treatments yielded a lower proportion of mature oocytes compared with
      the Long FSH treatment. Furthermore, FSH starvation led to an accumulation of
      larger lipid droplets in the ooplasm, indicating atresia. Our results indicate
      that a longer superstimulation period in beef cattle yields higher numbers and
      better-quality oocytes. 

PMID- 24942060
TI  - A luminescent heptanuclear DyIr6 complex showing field-induced slow magnetization
      relaxation.
AB  - The first example of iridium/lanthanide phosphonates, i.e.
      [DyIr6(ppy)12(bpp)2(bppH)4](CF3SO3).8H2O (1) (ppy(-) = 2-phenylpyridine, bpp(2-)
      = 2-pyridylphosphonate) is reported. It shows dual functions with the
      photoluminescence and field-induced slow magnetization relaxation originating
      from the Ir and Dy moieties, respectively. 

PMID- 24942061
TI  - Thermal ablation of saphenous veins is feasible and safe in patients older than
      75 years: A prospective study (EVTA study).
AB  - OBJECTIVES: To investigate the tolerance and safety of thermal ablation (TA),
      consisting of radiofrequency or endovenous laser (EVLA) of saphenous veins (SV)
      in elderly (group 1 >=75 years), compared with a control group (group 2 <75
      years). METHOD: An Observational multicenter-prospective study was conducted,
      under the aegis of the French and Swiss Societies of Phlebology (18 centers).
      Ninety patients were included in group 1, 617 in group 2 (mean age 80 years and
      53 years; 69% women in both groups), representing 863 SV. Mean trunk diameters
      were similar in both groups (small SV: 6 mm; great SV: 7 mm). In group 1,
      comorbidities were more frequent, particularly cardiac insufficiency, diabetes,
      history of thrombosis, and CEAP clinical class was significantly higher. RESULTS:
      EVLA was used in 86% of cases. Settings used were similar in both groups for each
      technique. Only 6% of TA was performed in an operating room for group 1 (14%
      group 2). Tumescent local anaesthesia (TLA) alone was used in 91% of cases in
      group 1 (85% group 2). The mean pain score was only 1.6 for the procedure itself
      (VASP 0-10; 10 max.) and 1.4 for the 10 days following the procedure. Side
      effects were few, but rate of paraesthesia was higher when general anaesthesia
      was used (11.8%) compared with TLA alone (2.2%). At three months, 100% of SV was
      occluded in group 1 (99.5% group 2), with high satisfaction score (9.3/10).
      CONCLUSION: TA is safe and effective in elderly; it should be performed strictly
      under TLA to minimize side effects.

PMID- 24942062
TI  - Burkitt's lymphoma masquerading as appendicitis--two case reports and review of
      the literature.
AB  - Two cases of Burkitt's lymphoma masquerading as appendicitis are reported herein.
      The diagnoses were made post-operatively from the appendix specimen in one case
      and from an ileocecal resection specimen for cecal fistula complicating an
      appendicectomy in the second case. These cases highlight the importance of
      routine histological examination of appendicectomy specimens. 

PMID- 24942063
TI  - Revisional surgery after laparoscopic adjustable gastric banding in a national
      Australian cohort.

PMID- 24942064
TI  - Understanding the interaction of DNA-RNA nucleobases with different ZnO
      nanomaterials.
AB  - Due to the potential application of different nanostructure materials in
      biomedical nanotechnologies, understanding the interaction between the inorganic
      nanoparticles and biological molecules at the atomic level is of paramount
      importance. We present here the results of our theoretical investigation of the
      interaction of different nucleotide bases--adenine (A), guanine (G), cytosine
      (C), thymine (T) and uracil (U) of deoxyribonucleic acid (DNA) and ribonucleic
      acid (RNA)--with different ZnO nanoparticles, such as ZnO nanowires (NWs),
      nanotubes (NTs), surfaces and quantum dots (QDs). As the size of the systems we
      studied is relatively large, we have used the self-consistent-charge density
      functional tight-binding (SCC-DFTB) method to optimize the complex systems. We
      have studied in detail the site-specific binding nature and the adsorption
      strength of these nucleobases with different ZnO nanoparticles. The calculated
      binding energy order and the interaction strength of nucleobases are very much
      dependent on the nature of the nanoparticle surfaces and are different for
      different nanostructures. In most of the cases ZnO prefers to bind either through
      the top site of the nucleobases or with the ring nitrogen atom having a lone pair
      relative to other binding sites of the bases.

PMID- 24942066
TI  - Epidemiological and clinical characteristics of children who died from hand, foot
      and mouth disease in Vietnam, 2011.
AB  - BACKGROUND: In 2011, a large outbreak of hand, foot and mouth disease (HFMD) in
      Vietnam resulted in 113,121 children seeking medical attention, of whom170 died.
      Understanding the epidemiology of fatal HFMD may improve treatment and help
      targeting prevention activities for vulnerable populations. We describe
      epidemiological and clinical characteristics of children who died from HFMD in
      Vietnam in 2011. METHODS: Clinical data were obtained through reviewing medical
      records of the deaths occurring from January through December 2011 in all
      hospitals in Vietnam. Hospitals reported any deaths among patients with
      laboratory-confirmed enterovirus (EV) infection to the Ministry of Health. Data
      were extracted from the national database. RESULTS: Of the 169 deaths reviewed
      for whom records were available, 87% were 3-year-old or younger, 69% were male,
      18% attended daycare, 89% lived in Southern Vietnam, and 85% of the deaths
      occurred between May-October 2011. One hundred thirty (77%) cases sought
      treatment in a hospital within three days of onset of illness. Symptoms at
      admission included fever (98%), myoclonus (66%), vomiting (53%), oral ulcers
      (50%) and vesicular erythema (50%). One hundred six (75%) cases had leukocytosis
      and 91 (54%) had hyperglycemia. One hundred three (61%) tested positive for EV,
      of which 84 (82%) were positive for EV71. CONCLUSIONS: Deaths associated with
      HFMD occurred throughout 2011 among males three years or younger who were cared
      for at home. The HFMD control program should focus on interventions at the
      household level. Clinicians should be alerted to symptoms suggestive of severe
      HFMD including fever, myoclonus, vomiting, oral ulcers and vesicles with high
      white blood cell count especially in young children.

PMID- 24942067
TI  - Intravitreal dexamethasone implant in patients with persistent macular edema of
      variable etiologies.
AB  - PURPOSE: To examine the effect of an intravitreal dexamethasone drug delivery
      system (DEX-DDS) in the treatment of persistent cystoid macular edema (CME) of
      different etiologies. METHODS: Thirty-seven eyes with persistent CME were treated
      with DEX-DDS and analyzed for changes in best-corrected visual acuity (BCVA) and
      optical coherence tomography. Eyes were categorized into three groups: diabetic
      macular edema (DME, n = 14), vein occlusion (n = 15) and uveitis (n = 7).
      RESULTS: The mean follow-up was 22 +/- 6.9 weeks. BCVA improved from 0.62 +/-
      0.38 to 0.35 +/- 0.29 logMAR (p < 0.0001). Central macular thickness decreased by
      184 +/- 246 um from baseline (p < 0.0001). In eyes where CME resolved and
      recurred, the average CME-free period was 11 weeks. The uveitis group showed
      faster CME resolution (2 weeks) and a longer CME-free period (20 weeks). Similar
      efficacy was shown for repeat DEX-DDS injections. The safety profile was good.
      CONCLUSION: DEX-DDS is beneficial in the treatment of persistent CME. In cases of
      uveitis, CME resolution is rapid, resulting in the longest effect duration, when
      compared with other CME etiologies.

PMID- 24942065
TI  - Genomes of Alteromonas australica, a world apart.
AB  - BACKGROUND: Alteromonas is a genus of marine bacteria that is very easy to
      isolate and grow in the laboratory. There are genomes available of the species
      Alteromonas macleodii from different locations around the world and an
      Alteromonas sp. isolated from a sediment in Korea. We have analyzed the genomes
      of two strains classified by 16S rRNA (>99% similarity) as the recently described
      species Alteromonas australica, and isolated from opposite ends of the world; A.
      australica DE170 was isolated in the South Adriatic (Mediterranean) at 1000 m
      depth while A. australica H17T was isolated from a sea water sample collected in
      St Kilda Beach, Tasman Sea. RESULTS: Although these two strains belong to a
      clearly different species from A. macleodii, the overall synteny is well
      preserved and the flexible genomic islands seem to code for equivalent functions
      and be located at similar positions. Actually the genomes of all the Alteromonas
      species known to date seem to preserve synteny quite well with the only exception
      of the sediment isolate SN2. Among the specific metabolic features found for the
      A. australica isolates there is the degradation of xylan and production of
      cellulose as extracellular polymeric substance by DE170 or the potential
      ethanol/methanol degradation by H17T. CONCLUSIONS: The genomes of the two A.
      australica isolates are not more different than those of strains of A. macleodii
      isolated from the same sample. Actually the recruitment from metagenomes
      indicates that all the available genomes are found in most tropical-temperate
      marine samples analyzed and that they live in consortia of several species and
      multiple clones within each. Overall the hydrolytic activities of the Alteromonas
      genus as a whole are impressive and fit with its known capabilities to exploit
      sudden inputs of organic matter in their environment.

PMID- 24942068
TI  - Carbohydrate availability and exercise training adaptation: too much of a good
      thing?
AB  - Traditional nutritional approaches to endurance training have typically promoted
      high carbohydrate (CHO) availability before, during and after training sessions
      to ensure adequate muscle substrate to meet the demands of high daily training
      intensities and volumes. However, during the past decade, data from our
      laboratories and others have demonstrated that deliberately training in
      conditions of reduced CHO availability can promote training-induced adaptations
      of human skeletal muscle (i.e. increased maximal mitochondrial enzyme activities
      and/or mitochondrial content, increased rates of lipid oxidation and, in some
      instances, improved exercise capacity). Such data have led to the concept of
      'training low, but competing high' whereby selected training sessions are
      completed in conditions of reduced CHO availability (so as to promote training
      adaptation), but CHO reserves are restored immediately prior to an important
      competition. The augmented training response observed with training-low
      strategies is likely regulated by enhanced activation of key cell signalling
      kinases (e.g. AMPK, p38MAPK), transcription factors (e.g. p53, PPARdelta) and
      transcriptional co-activators (e.g. PGC-1alpha), such that a co-ordinated up
      regulation of both the nuclear and mitochondrial genomes occurs. Although the
      optimal practical strategies to train low are not currently known, consuming
      additional caffeine, protein, and practising CHO mouth-rinsing before and/or
      during training may help to rescue the reduced training intensities that
      typically occur when 'training low', in addition to preventing protein breakdown
      and maintaining optimal immune function. Finally, athletes should practise 'train
      low' workouts in conjunction with sessions undertaken with normal or high CHO
      availability so that their capacity to oxidise CHO is not blunted on race day.

PMID- 24942070
TI  - Comparison of cryoprotective effects of lycopene and cysteamine in different
      cryoprotectants on bull semen and fertility results.
AB  - The objectives of this study were to compare glycerol and ethylene glycol at
      different concentrations as cryoprotectants and lycopene or cysteamine
      (with/without) as antioxidants in Tris extender for bull semen. Twenty-four
      ejaculates were obtained from three bulls. Each ejaculate was split into four
      equal aliquots and diluted using both of the Tris extenders with glycerol (5% or
      7%) or ethylene glycol (3% or 5%). After that, each extenders were split into
      three equal aliquots and added using both of the cysteamine 5 mm or lycopene 500
      MUg/ml, and control (without additives). The addition of 7% glycerol with
      cysteamine, 5% ethylene glycol with cysteamine and 3% ethylene glycol with
      cysteamine groups gave the lowest CASA motility than the other groups. However,
      7% glycerol and 7% glycerol with lycopene resulted in a better rate of CASA
      progressive motility compared with that of other groups. Generally, all the
      lycopene groups signed better protective effects on acrosome and total morphology
      than the other groups. Glycerol 7% and 3% ethylene glycol with lycopene groups
      yielded to slight higher percentages of membrane integrity assessed by HOST than
      that of the other groups, but 7% glycerol with cysteamine and 3% ethylene glycol
      with cysteamine showed the worst percentages of membrane integrity. Glycerol 7%
      and 5% glycerol with lycopene gave rise to a higher value of VAP, VSL and VCL
      compared with that of the other groups. On the contrary, adding to 5% glycerol
      with cysteamine showed negative effect for VAP, VSL, VCL and ALH values. All
      cryoprotectant groups with lycopene decreased chromatin damage than the other
      groups. Ethylene glycol 3% led to lower non-return rates of inseminated cows.
      However, this result was not considered to be statistically important. 

PMID- 24942069
TI  - RND transporters protect Corynebacterium glutamicum from antibiotics by
      assembling the outer membrane.
AB  - Corynebacterium-Mycobacterium-Nocardia (CMN) group are the causative agents of a
      broad spectrum of diseases in humans. A distinctive feature of these Gram
      positive bacteria is the presence of an outer membrane of unique structure and
      composition. Recently, resistance-nodulation-division (RND) transporters
      (nicknamed MmpLs, Mycobacterial membrane protein Large) have emerged as major
      contributors to the biogenesis of the outer membranes in mycobacteria and as
      promising drug targets. In this study, we investigated the role of RND
      transporters in the physiology of Corynebacterium glutamicum and analyzed
      properties of these proteins. Our results show that in contrast to Gram-negative
      species, in which RND transporters actively extrude antibiotics from cells, in C.
      glutamicum and relatives these transporters protect cells from antibiotics by
      playing essential roles in the biogenesis of the low-permeability barrier of the
      outer membrane. Conditional C. glutamicum mutants lacking RND proteins and with
      the controlled expression of either NCgl2769 (CmpL1) or NCgl0228 (CmpL4) are
      hypersusceptible to multiple antibiotics, have growth deficiencies in minimal
      medium and accumulate intracellularly trehalose monocorynomycolates, free
      corynomycolates, and the previously uncharacterized corynomycolate-containing
      lipid. Our results also suggest that similar to other RND transporters,
      Corynebacterial membrane proteins Large (CmpLs) functions are dependent on a
      proton-motive force. 

PMID- 24942071
TI  - Back-carrying infants to prevent developmental hip dysplasia and its sequelae: is
      a new public health initiative needed?
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is rarely encountered in the
      native sub-Saharan African population. We present a retrospective review of the
      incidence of symptomatic DDH in Malawi and a systematic review of the role of
      back-carrying as a potential influence of prevalence in this population group.
      METHODS: We retrospectively reviewed the diagnosis and management of all infants
      seen at the Beit CURE International Hospital, Malawi and its mobile clinics, from
      November 2002 to September 2012. In addition, methodical review of the literature
      using the Preferred Reporting Items for Systematic Reviews and Meta-analyses
      checklist and algorithm was performed. RESULTS: A total of 40,683 children aged
      less than 16 years were managed at our institute over a 10-year period, of which
      9842 children underwent surgery. No infant presented with, or underwent surgical
      intervention, for symptomatic DDH. CONCLUSIONS: The majority of mothers in Malawi
      back-carry their infants during the first 2 to 24 months of life, in a position
      that is similar to that of the Pavlik harness. We believe this to be the prime
      reason for the low incidence of DDH in the country. In addition, there is
      established evidence indicating that swaddling, the opposite position to back
      carrying, causes an increase in the incidence of DDH. There is a need for the
      establishment of a large clinical trial into back-carrying and prevention of DDH
      in non-African population groups. LEVEL OF EVIDENCE: Level II.

PMID- 24942072
TI  - Iatrogenic left ventricular-right atrial communication after tricuspid
      annuloplasty; a case report.
AB  - A 75-year-old man (Asian, Japanese) was readmitted for examination of a heart
      murmur and haemolytic anemia 3 months after mitral valve and tricuspid
      annuloplasties and coronary artery bypass. A new systolic murmur was heard, and
      echocardiography showed a high-velocity jet originating from the left ventricular
      outflow tract and extending to the right atrium, a small defect between the left
      ventricle and the right atrium. No periprosthetic leaks were found in the mitral
      position. We judged that surgical repair of the defect was essential to treat
      mechanical haemolysis. At operation, we found a communication (3 mm in diameter)
      just beneath the detached prosthetic ring at the anteroseptal commissure of the
      tricuspid valve. After partially removing the tricuspid ring from the
      anteroseptal commissure area, the defect was closed using a single mattress
      suture with pledget. In this case, the tricuspid annuloplasty stitch in the
      atrioventricular region was probably placed on the membranous septum rather than
      on the tricuspid annulus. A tear then occurred in the atrioventricular membranous
      septum, leading to left ventricular-right atrial communication. 

PMID- 24942073
TI  - Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of
      chronic hepatitis C infection.
AB  - Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being
      discussed, but both the immune system and the virus are involved. The aim of this
      study was to evaluate intrahepatic viral infection, apoptosis and portal and
      periportal/interface infiltrate in paediatric and adult patients to elucidate the
      pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and
      TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+)
      lymphocytes infiltrating portal and periportal/interface tracts were evaluated in
      27 paediatric and 32 adult liver samples by immunohistochemistry or
      immunofluorescence. The number of infected hepatocytes was higher in paediatric
      than in adult samples (p 0.0078). In children, they correlated with apoptotic
      hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p
      0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were
      associated with the severity of fibrosis. In adults, activated caspase-3(+) cell
      count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and
      Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric
      CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+)
      hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated
      caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated
      with hepatitis severity (p < 0.0001) and correlated with inflammatory activity
      (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be
      involved in CHC pathogenesis of both paediatric and adult patients. However,
      liver injury in paediatric CHC would be largely associated with a viral
      cytopathic effect mediated by apoptosis, while in adults it would be mainly
      associated with an exacerbated immune response.

PMID- 24942074
TI  - The powdery mildew resistance gene Pm8 derived from rye is suppressed by its
      wheat ortholog Pm3.
AB  - The powdery mildew resistance gene Pm8 derived from rye is located on a 1BL.1RS
      chromosome translocation in wheat. However, some wheat lines with this
      translocation do not show resistance to isolates of the wheat powdery mildew
      pathogen avirulent to Pm8 due to an unknown genetically dominant suppression
      mechanism. Here we show that lines with suppressed Pm8 activity contain an intact
      and expressed Pm8 gene. Therefore, the absence of Pm8 function in certain 1BL.1RS
      containing wheat lines is not the result of gene loss or mutation but is based on
      suppression. The wheat gene Pm3, an ortholog of rye Pm8, suppressed Pm8-mediated
      powdery mildew resistance in lines containing Pm8 in a transient single-cell
      expression assay. This result was further confirmed in transgenic lines with
      combined Pm8 and Pm3 transgenes. Expression analysis revealed that suppression is
      not the result of gene silencing, either in wheat 1BL.1RS translocation lines
      carrying Pm8 or in transgenic genotypes with both Pm8 and Pm3 alleles. In
      addition, a similar abundance of the PM8 and PM3 proteins in single or double
      homozygous transgenic lines suggested that a post-translational mechanism is
      involved in suppression of Pm8. Co-expression of Pm8 and Pm3 genes in Nicotiana
      benthamiana leaves followed by co-immunoprecipitation analysis showed that the
      two proteins interact. Therefore, the formation of a heteromeric protein complex
      might result in inefficient or absent signal transmission for the defense
      reaction. These data provide a molecular explanation for the suppression of
      resistance genes in certain genetic backgrounds and suggest ways to circumvent it
      in future plant breeding. 

PMID- 24942075
TI  - Special issue on stem cells.

PMID- 24942078
TI  - CYP1B1 gene mutations causing primary congenital glaucoma in Tunisia.
AB  - Primary congenital glaucoma (PCG) is responsible for a significant proportion of
      childhood blindness in Tunisia. Early prevention based on genetic diagnosis is
      therefore required. This study sought to determine the frequency of CYP1B1
      (cytochrome P450, family 1, subfamily B, polypeptide 1) mutations in 18 PCG
      patients, recruited from Central and Southern of Tunisia. Genomic DNA was
      extracted and the coding regions of CYP1B1 were analysed by direct sequencing. A
      phylogenetic network of CYP1B1 haplotypes was drawn using the median-joining
      algorithm. Sequence analysis revealed a "tetra-allelic mutation" (two novel
      mutations, p.F231I and p.P437A in the homozygous state) in one patient. The
      healthy members of his family carried those variations on the same allele. Two
      previously described mutations p.G61E and c.535delG were also identified in the
      homozygous state in seven and two probands, respectively. Seven single-nucleotide
      polymorphisms were identified and used to generate haplotypes. Our results showed
      that the CYP1B1 mutations were present in 55% of Tunisian PCG patients' alleles.
      Haplotype analysis allowed us to define the proto-haplotype and to confirm
      historical migratory flows. Establishment of PCG genetic aetiology in Tunisia
      will improve genetic diagnosis and counselling. 

PMID- 24942077
TI  - Visualizing active membrane protein complexes by electron cryotomography.
AB  - Unravelling the structural organization of membrane protein machines in their
      active state and native lipid environment is a major challenge in modern cell
      biology research. Here we develop the STAMP (Specifically TArgeted Membrane
      nanoParticle) technique as a strategy to localize protein complexes in situ by
      electron cryotomography (cryo-ET). STAMP selects active membrane protein
      complexes and marks them with quantum dots. Taking advantage of new electron
      detector technology that is currently revolutionizing cryotomography in terms of
      achievable resolution, this approach enables us to visualize the three
      dimensional distribution and organization of protein import sites in
      mitochondria. We show that import sites cluster together in the vicinity of
      crista membranes, and we reveal unique details of the mitochondrial protein
      import machinery in action. STAMP can be used as a tool for site-specific
      labelling of a multitude of membrane proteins by cryo-ET in the future. 

PMID- 24942079
TI  - ABCA1 rs4149313 polymorphism and susceptibility to coronary heart disease: a meta
      analysis.
AB  - Many existing studies have demonstrated that common polymorphisms in the ABCA1
      gene may play important roles in the development and progression of coronary
      heart disease (CHD), but individually published results are inconclusive. This
      meta-analysis aimed to derive a more precise estimation of the relationship
      between the ABCA1 rs4149313 polymorphism and CHD risk. We searched the CISCOM,
      CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM
      databases from inception through 1 September 2013. Meta-analysis was performed
      using the STATA 12.0 software. Odds ratios (OR) and their 95% confidence
      intervals (CI) were estimated. Eleven case-control studies were included with a
      total of 5416 CHD patients and 20,897 healthy controls. Our meta-analysis results
      revealed that the ABCA1 rs4149313 polymorphism may be associated with an
      increased risk of CHD. Subgroup analysis by ethnicity suggested that there were
      significant associations between the ABCA1 rs4149313 polymorphism and an
      increased risk of CHD in Asian populations, but not in Caucasian populations (all
      P > 0.05). Meta-regression analyses showed that ethnicity may be a main source of
      heterogeneity. The present meta-analysis suggests that the ABCA1 rs4149313
      polymorphism may contribute to the risk of CHD, especially in Asian populations. 

PMID- 24942081
TI  - Rank-based tests for identifying multiple genetic variants associated with
      quantitative traits.
AB  - We consider the analysis of multiple genetic variants within a gene or a region
      that are expected to confer risks to human complex diseases with quantitative
      traits, where the trait values do not follow the normal distribution even after
      some transformations. We rank the phenotypic values, calculate a score to measure
      the trend effect of a particular allele for each marker, and then construct three
      statistics based on the quadratic frameworks of methods Hotelling T(2) , the
      summation of squared univariate statistic and the inverse of the square root
      weighted statistics to combine the scores for different marker loci. Simulation
      results show that the above three test statistics can control the type I error
      rate well and are more robust than standard tests constructed based on linear
      regression. Application to GAW16 data for rheumatoid arthritis successfully
      detects the association between the HLA-DRB1 gene and anticyclic citrullinated
      protein measure, while the standard methods based on normal assumption cannot
      detect this association. 

PMID- 24942080
TI  - On the performance of multiple imputation based on chained equations in tackling
      missing data of the African alpha3.7 -globin deletion in a malaria association
      study.
AB  - Multiple imputation based on chained equations (MICE) is an alternative missing
      genotype method that can use genetic and nongenetic auxiliary data to inform the
      imputation process. Previously, MICE was successfully tested on strongly linked
      genetic data. We have now tested it on data of the HBA2 gene which, by the
      experimental design used in a malaria association study in Tanzania, shows a high
      missing data percentage and is weakly linked with the remaining genetic markers
      in the data set. We constructed different imputation models and studied their
      performance under different missing data conditions. Overall, MICE failed to
      accurately predict the true genotypes. However, using the best imputation model
      for the data, we obtained unbiased estimates for the genetic effects, and
      association signals of the HBA2 gene on malaria positivity. When the whole data
      set was analyzed with the same imputation model, the association signal increased
      from 0.80 to 2.70 before and after imputation, respectively. Conversely,
      postimputation estimates for the genetic effects remained the same in relation to
      the complete case analysis but showed increased precision. We argue that these
      postimputation estimates are reasonably unbiased, as a result of a good study
      design based on matching key socio-environmental factors. 

PMID- 24942082
TI  - Use of a dissolved oxygen microsensor for assessing the viability and thickness
      of microbial biofilm on root surfaces.
AB  - AIM: To evaluate the use of a dissolved oxygen microsensor (DOMS) for assessing
      the viability and thickness of microbial biofilms on the apical external surface
      of contaminated human tooth roots. METHODOLOGY: Apical biofilm formation was
      evaluated in 15 roots contaminated in vitro with a polymicrobial mixture of
      Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Candida
      albicans for 7, 21 and 60 days and in three freshly extracted roots with
      associated radiographically visible periapical lesions. In each root, the
      thickness and viability (measured by the amount of dissolved oxygen) of biofilm
      formed on the apical 2 mm were examined with the DOMS. Scanning electron
      microscopy (SEM) was used as an auxiliary analysis to confirm the existence of
      the biofilms detected by the DOMS. RESULTS: The DOMS detected dissolved oxygen on
      the biofilms formed on the three residual roots up to thickness of 375 MUm, 480
      MUm and 1650 MUm. In the 15 roots contaminated in vitro, the DOMS detected
      dissolved oxygen in six specimens up to thicknesses from 75 to 250 MUm, and the
      intensity of the metabolic activity (biofilm thickness) was directly proportional
      to the contamination time. SEM confirmed the presence of biofilm in all roots.
      CONCLUSION: The dissolved oxygen microsensor allowed the measurement of the
      amount of dissolved oxygen in the biofilm, which is indicative of the intensity
      of the microbial metabolic activity (viability), correlating the results with
      biofilm thickness. The DOMS was effective in freshly extracted roots, but had
      limitations in roots contaminated in vitro after short periods (7 and 21 days) of
      contamination.

PMID- 24942084
TI  - Adverse health effects of testosterone deficiency (TD) in men.
AB  - Testosterone and its metabolite, 5alpha-dihydrotestosterone are critical
      metabolic and vascular hormones, which regulate a host of biochemical pathways
      including carbohydrate, lipid and protein metabolism and modulate vascular
      function. Testosterone deficiency (TD) is a well-recognized medical condition
      with important health implications. TD is associated with a number of co
      morbidities including increased body weight, adiposity and increased waist
      circumference, insulin resistance (IR) and type 2 diabetes mellitus (T2DM),
      hypertension, inflammation, atherosclerosis and cardiovascular disease, erectile
      dysfunction (ED) and increased incidence of mortality. In this review, we
      summarize the data in the literature on the prevalence of TD and its association
      with the various co-morbidities and suggest that T therapy is necessary to
      improve health outcomes in men with TD. 

PMID- 24942083
TI  - How do we manage cardiopulmonary bypass coagulopathy?
AB  - BACKGROUND: Patients who undergo cardiopulmonary bypass (CPB) are at risk for
      coagulopathy. Suboptimal turnaround time (TAT) of laboratory coagulation testing
      results in empiric administration of blood products to treat massive bleeding. We
      describe our initiative in establishing the coagulation-based hemotherapy (CBH)
      service, a clinical pathology consultation service that uses rapid TAT
      coagulation testing and provides comprehensive assessment of bleeding in patients
      undergoing CPB. A transfusion algorithm that treats the underlying cause of
      coagulopathy was developed. STUDY DESIGN AND METHODS: The coagulation testing
      menu includes all aspects of coagulopathy with close proximity of the laboratory
      to the operating room to allow for rapid test results. The hemotherapy
      pathologist monitors laboratory results at several stages in surgery and uses a
      comprehensive algorithm to monitor a patient's hemostasis. The optimal number and
      type of blood products are selected when the patient is taken off CPB. RESULTS:
      The CBH service was consulted for 44 ventricular assist device implants, 30 heart
      transplants, and 31 other cardiovascular surgeries from May 2012 through November
      2013. The TAT for laboratory tests was 15 minutes for complete blood count,
      antithrombin, and coagulation panel and 30 minutes for VerifyNow and
      thromboelastography, in comparison to 45 to 60 minutes in normal settings. The
      transfusion algorithms were used with optimal administration of blood components
      with preliminary data suggestive of reduced blood product usage and better
      patient outcomes. CONCLUSION: We described the successful introduction of a novel
      pathology consultation service that uses a rapid TAT coagulation testing menu
      with transfusion algorithms for improved management of CPB patients.

PMID- 24942085
TI  - Assessment of speech in early-onset ataxia: a pilot study.
AB  - AIM: The aim of the study was to determine whether paediatric ataxia speech
      subscores are reliably applicable for international early-onset ataxia (EOA)
      databases. If so, we reasoned that ataxia speech subscores should be associated
      with ataxia scores and involve high interobserver agreement, including those for
      internationally applicable Scale for Assessment and Rating of Ataxia (SARA)
      syllable repetition tasks (SARASRT). METHOD: Three independent paediatric
      neurologists and a speech therapist scored speech in 52 healthy children (mean
      age 10y, range 4-16y) and 40 individuals with EOA (mean age 15y, range 5-34y). We
      compared ataxia speech subscores for the association with age and ataxia scores
      as well as interobserver reliability. RESULTS: In healthy children, ataxia speech
      subscores were moderately associated with age (International Cooperative Ataxia
      Rating Scale [ICARS]: r=-0.515; SARA: r=-0.321; p<0.05) and with ataxia scores
      (ICARS: r=0.552; SARA: r=0.336; p<0.05), and revealed slight to moderate
      interobserver agreement (ICARS-intraclass correlation coefficient [ICC]: 0.380;
      SARA-ICC: 0.185; SARASRT-ICC: 0.509). In EOA, speech subscores have a strong
      association with ataxia scores (ICARS: r=0.735; SARA: r=0.730; p<0.001) and
      revealed substantial to nearly perfect interobserver agreement (ICARS-ICC: 0.812;
      SARA-ICC: 0.854; SARASRT-ICC: 0.724). INTERPRETATION: Early-onset ataxia speech
      subscores are associated with ataxia and also reveal high interobserver
      agreement, including those internationally applicable to SARASRT. We conclude
      that SARASRT appears to be applicable for EOA databases. However, before syllable
      repetition tasks are included, we would advise to wait for the results published
      by the international Childhood Ataxia and Cerebellar Group.

PMID- 24942086
TI  - Hypnic headache: a review of clinical features, therapeutic options and outcomes.
AB  - BACKGROUND: Hypnic headache (HH), first reported in 1988, is a rare sleep-related
      headache disorder. In 2013 a new diagnostic criteria was proposed for HH in the
      International Classification of Headache Disorders, the third version beta (ICHD
      3beta). PURPOSE: This review aimed to update the clinical characteristics,
      therapeutic options and clinical outcomes in patients with HH and also validate
      the new diagnostic criteria. METHODS: Based on a literature search in the major
      medical databases, we analyzed all case reports or case series on HH that have
      been published since the first description by Raskin. Except for symptomatic
      patients, all reported patients were included regardless of which diagnostic
      criteria were adopted. Four studies that reported the field-testing results of
      the ICHD-2 criteria were selected to validate the new ICHD-3beta criteria.
      RESULTS: In total, 250 adult and five childhood patients are described in this
      review. The majority of patients were elderly and their ages of onset were
      typically more than 50 years old (92%). Approximately 7.7% of patients had some
      trigeminal autonomic features, which are not permitted in the ICHD-3beta
      criteria. Compared with the ICHD-2 criteria, the diagnostic rate under the new
      criteria increased from 65% to 85% in recently reported cases. Randomized control
      trials both for acute and prophylactic treatment are lacking. Based on
      observational studies, the most effective acute treatment is caffeine and
      prophylactic medications in use are lithium, caffeine and indomethacin. Without
      treatment, the disease course is usually protracted but spontaneous remission did
      occur in 12 patients (4.8%). In those treated with prophylactic agents, no
      recurrence was noted in 43% of patients, even following withdrawal of medication.
      CONCLUSIONS: The new ICHD-3beta criteria are more sensitive and exhaustive for HH
      than the ICHD-2 criteria. Prophylactic treatment provides better outcomes;
      however, randomized controlled studies for treatment are needed to further verify
      the efficacy of the different drugs.

PMID- 24942087
TI  - Improving migraine headache management in emergency departments: the time has
      come.

PMID- 24942088
TI  - The P450-type carotene hydroxylase PuCHY1 from Porphyra suggests the evolution of
      carotenoid metabolism in red algae.
AB  - Carotene hydroxylases catalyze the hydroxylation of alpha- and beta-carotene
      hydrocarbons into xanthophylls. In red algae, beta-carotene is a ubiquitously
      distributed carotenoid, and hydroxylated carotenoids such as zeaxanthin and
      lutein are also found. However, no enzyme with carotene hydroxylase activity had
      been previously identified in red algae. Here, we report the isolation of a gene
      encoding a cytochrome P450-type carotene hydroxylase (PuCHY1) from Porphyra
      umbilicalis, a red alga with an ancient origin. Sequence comparisons found PuCHY1
      belongs to the CYP97B subfamily, which has members from different photosynthetic
      organisms ranging from red algae to land plants. Functional complementation in
      Escherichia coli suggested that PuCHY1 catalyzed the conversion from beta
      carotene to zeaxanthin. When we overexpressed PuCHY1 in the Arabidopsis thaliana
      chy2 mutant, pigment analysis showed a significant accumulation of hydroxylated
      carotenoids, including neoxanthin, violaxanthin, and lutein in the leaves of
      transgenic plants. These results confirmed a beta-hydroxylation activity of
      PuCHY1, and also suggested a possible epsilon-hydroxylation function. The pigment
      profile and gene expression analyses of the algal thallus under high-light stress
      suggested that P. umbilicalis is unlikely to operate a partial xanthophyll cycle
      for photoprotection. 

PMID- 24942089
TI  - Cerebrovascular responses during rowing: Do circadian rhythms explain morning and
      afternoon performance differences?
AB  - The purpose of this study was to characterize cerebrovascular responses to rowing
      exercise, investigating whether their diurnal variation might explain performance
      differences across a day. Twelve male rowers completed incremental rowing
      exercise and a 2000-m ergometer time trial at 07:00 h and 16:00 h, 1 week apart,
      while middle cerebral artery velocity (MCAv), cerebral (prefrontal), and muscular
      (vastus lateralis) tissue oxygenation and hemoglobin volume (via near-infrared
      spectroscopy), heart rate, and pressure of end-tidal CO2 (PET CO2) were recorded.
      MCAv was 20-25% above resting levels (68 +/- 12 cm/s) during submaximal and
      maximal exercise intensities, despite PET CO2 being reduced during maximal
      efforts (down ~ 0.5-0.8 kPa); thus revealing a different perfusion profile to the
      inverted-U observed in other exercise modes. The afternoon time trial was 3.4 s
      faster (95% confidence interval 0.9-5.8 s) and mean power output 3.2% higher (337
      vs 347 W; P = 0.04), in conjunction with similar exercise-induced elevations in
      MCAv (P = 0.60) and reductions in cerebral oxygenation (TOI) (P = 0.12). At the
      muscle, afternoon trials involved similar oxygen extraction (HHb volume and TOI)
      albeit from a relatively lower total Hb volume (P < 0.01). In conclusion, rowing
      performance was better in the afternoon, but not in conjunction with differences
      in MCAv or exercise-induced differences in cerebral oxygenation.

PMID- 24942090
TI  - Melatonin identified in meats and other food stuffs: potentially nutritional
      impact.
AB  - Melatonin has been identified in primitive photosynthetic bacteria, fungi,
      plants, and animals including humans. Vegetables, fruits, cereals, wine, and
      beers all contain melatonin. However, the melatonin content in meats has not been
      reported previously. Here, for the first time, we report melatonin in meats,
      eggs, colostrum, and in other edible food products. The levels of melatonin
      measured by HPLC, in lamb, beef, pork, chicken, and fish, are comparable to other
      food stuffs (in the range of ng/g). These levels are significantly higher than
      melatonin concentrations in the blood of vertebrates. As melatonin is a potent
      antioxidant, its presence in the meat could contribute to shelf life duration as
      well as preserve their quality and taste. In addition, the consumption of these
      foods by humans or animals could have health benefits considering the important
      functions of melatonin as a potent free radical scavenger and antioxidant. 

PMID- 24942091
TI  - Misperception of body weight and associated factors.
AB  - The prevalence of obesity is increasing. In Korea, this is especially true of men
      in general, and women of low socioeconomic status. Misperception of body weight
      poses a barrier to the prevention of obesity. In this study, the misperception of
      body weight in relation to actual body weight and associated factors in Korean
      adults was evaluated. Data from 7162 adults who participated in the 2009 Korean
      National Health and Nutrition Examination Survey were analyzed. Misperception of
      body weight was substantial in Koreans, with 48.9% underestimating and 6.8%
      overestimating their weight status. More men than women underestimated their
      weight status. Weight perception in women was affected more by sociodemographic
      characteristics. Women's underestimation was positively associated with older
      age, marital status, and lower socioeconomic status. This suggests that
      increasing public awareness of healthy weight will be helpful to counteract the
      current obesity epidemic in Korea. 

PMID- 24942092
TI  - Theoretical aspects of WS2 nanotube chemical unzipping.
AB  - Theoretical analysis of experimental data on unzipping multilayered WS2 nanotubes
      by consequent intercalation of lithium atoms and 1-octanethiol molecules [C.
      Nethravathi, et al., ACS Nano, 2013, 7, 7311] is presented. The radial expansion
      of the tube was described using continuum thin-walled cylinder approximation with
      parameters evaluated from ab initio calculations. Assuming that the attractive
      driving force of the 1-octanethiol molecule is its reaction with the intercalated
      Li ions ab initio calculations of a 1-octanethiol molecule bonding with Li(+)
      were carried out. In addition, the non-chemical interactions of the 1-octanethiol
      dipole with an array of positive point charges representing Li(+) were taken into
      account. Comparing between the energy gain from these interactions and the
      elastic strain energy of the nanotube allows us to evaluate a value for the tube
      wall deformation after the implantation of 1-octanethiol molecules. The ab initio
      molecular dynamics simulation confirmed our estimates and demonstrated that a
      strained WS2 nanotube, with a decent concentration of 1-octanethiol molecules,
      should indeed be unzipped into the WS2 nanoribbon.

PMID- 24942093
TI  - The CAD-CAM technique for mandibular reconstruction: an 18 patients oncological
      case-series.
AB  - BACKGROUND: Modern techniques for mandibular reconstruction, such as CAD-CAM,
      offer new solutions for planning of reconstructive surgery in relation to the
      aesthetic outcome and the prosthetic rehabilitation. METHODS: CAD-CAM
      reconstruction procedures using vascularised bone free-flap transfers and
      surgical guides to cut the mandible and fibula were performed in 18 cases of
      neoplasms. The planned surgery was used to design and manufacture customised
      surgical devices. RESULTS: The mean follow-up was 12 months. All patients, except
      one, are alive without disease at the time of writing. Reconstructive
      microvascular flap survival was 100%. No major or minor microvascular
      complication occurred. No donor site complication was observed. CONCLUSIONS: CAD
      CAM technology is a very useful way to obtain the native morphology of the
      mandible, especially when both bi-dimensional and tri-dimensional defects occur.
      The reconstruction protocol presented offers several benefits and few
      disadvantages, which are discussed in the article.

PMID- 24942094
TI  - Piezoelectric ultrasonic bone surgery system in the extraction surgery of
      supernumerary teeth.
AB  - INTRODUCTION: The anterior maxillary region is a common site for supernumerary
      teeth. The aim of this study was to compare the use of piezoelectric ultrasonic
      bone surgery for the extraction of supernumerary teeth and the use of traditional
      method using bone chisels. METHODS: 60 patients with supernumerary anterior
      maxillary teeth were considered in this study. They were randomly divided into
      two groups: 1) the control group, in which the supernumerary teeth were extracted
      using the traditional bone chisels method; 2) the experimental group, in which
      the supernumerary teeth were extracted using a piezoelectric ultrasonic bone
      surgery system. The operative time, amount of bleeding and post-operative pain
      were quantified and compared; in addition, the post-operative swelling was
      evaluated. RESULTS: We observed a significant decrease (P < 0.01) in the amount
      of bleeding and post-operative pain in the experimental group respect to the
      control group; but the operative time was significantly increased (P < 0.01) with
      the use of piezoelectric system. In addition, post-operative swelling resolved
      more quickly in the experimental group. CONCLUSION: Although the operative time
      for the extraction of the maxillary anterior supernumerary teeth was longer using
      the piezoelectric ultrasonic bone surgery system, the amount of bleeding and the
      post-operative complications were less, so this system could be considered an
      appropriate surgical method for the extraction of supernumerary teeth.

PMID- 24942095
TI  - RFC1 and non-syndromic cleft lip with or without cleft palate: an association
      based study in Italy.
AB  - The molecular basis of orofacial development is largely unknown and needs to be
      unravelled. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the
      most common craniofacial malformation, with an incidence of about 1/700 live
      births, although variable according to ethnicity. Being a multifactorial disease,
      it arises as a result of an interplay between genetic and environmental factors.
      Several approaches have been developed to identify susceptibility genes. Genes
      belonging to the folate/homocysteine pathway are attracting increasing interest
      because folate supplementation before and during early pregnancy can reduce the
      risk of NSCL/P. We performed a family based association study in order to assess
      if a genetic variant of RFC1 could be involved in NSCL/P onset. We genotyped 404
      unrelated probands and their relatives for three biallelic polymorphic variants
      (rs1051266, rs4818789 and rs3788205), that were selected because they produced
      conflicting results on previous investigations. Evidence of association was found
      between the investigated polymorphisms and NSCL/P in our sample of the Italian
      population, albeit with weak significance levels. Results from this investigation
      provided a support of previous studies suggesting a role of RFC1 in NSCL/P
      aetiology, reinforcing the concept that genetic predisposition to NSCL/P varies
      enormously within different ethnic groups. 

PMID- 24942096
TI  - Buccal sulcus versus intranasal approach for postoperative periorbital oedema and
      ecchymosis in lateral nasal osteotomy.
AB  - BACKGROUND: Lateral osteotomies are used in rhinoplasty to narrow the nasal
      bones, close the open roof deformity after hump removal, and achieve symmetry of
      an asymmetrical framework. But this procedure causes periorbital oedema &
      ecchymosis. Different techniques have been described for lateral osteotomy.
      OBJECTIVE: To compare the postoperative ecchymosis and oedema after buccal sulcus
      lateral osteotomy versus intranasal lateral osteotomy. METHODS AND MATERIALS: In
      a prospective experimental study, buccal sulcus approach was performed on the
      right side and an intranasal approach performed on the left side of patients
      randomly. Then blind analysis of postoperative photographs was performed to
      determine the incidence of oedema and ecchymosis on each side. RESULTS: Fifty
      patients were enrolled in the study after exclusion of unfit patients. On the
      right side (buccal approach osteotomies), a significantly lower incidence of
      upper and lower eyelid oedema and upper eyelid ecchymosis was seen on both the
      2nd day and after 7th day (P < 0.05). The odds ratio of progression of ecchymosis
      was 2.66 (OR = 2.66, 95% CI: 1.09-5.52, p = 0.048) in intranasal group compare to
      buccal sulcus group. No significant complication observed. CONCLUSION: The buccal
      sulcus approach is a safe method for lateral osteotomy with a lower rate of
      postoperative oedema and ecchymosis and no significant complications.

PMID- 24942097
TI  - Sciatic nerve regeneration induced by transplantation of in vitro bone marrow
      stromal cells into an inside-out artery graft in rat.
AB  - Traumatic injury to peripheral nerves results in considerable motor and sensory
      disability. Several research groups have tried to improve the regeneration of
      traumatized nerves by invention of favorable microsurgery. Effect of
      undifferentiated bone marrow stromal cells (BMSCs) combined with artery graft on
      peripheral nerve regeneration was studied using a rat sciatic nerve regeneration
      model. A 10-mm sciatic nerve defect was bridged using an artery graft (IOAG)
      filled with undifferentiated BMSCs (2 * 10(7) cells/mL). In control group, the
      graft was filled with phosphated buffer saline alone. The regenerated fibers were
      studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was
      based on behavioral, functional (Walking Track Analysis), electrophysiological,
      histomorphometric and immuohistochemical (Schwann cell detection by S-100
      expression) criteria. The behavioral, functional and electrophysiological studies
      confirmed significant recovery of regenerated axons in IOAG/BMSC group (P <
      0.05). Quantitative morphometric analyses of regenerated fibers showed the number
      and diameter of myelinated fibers in IOAG/BMSC group were significantly higher
      than in the control group (P < 0.05). This demonstrates the potential of using
      undifferentiated BMSCs combined with artery graft in peripheral nerve
      regeneration without limitations of donor-site morbidity associated with
      isolation of Schwann cells. It is also cost saving due to reduction in interval
      from tissue collection until cell injection, simplicity of laboratory procedures
      compared to differentiated BMSCs and may have clinical implications for the
      surgical management of patients after facial nerve transection.

PMID- 24942098
TI  - Management of frontal sinus fractures--treatment decision based on metric
      dislocation extent.
AB  - The treatment of frontal sinus fractures is still a matter of research in
      neurosurgical and craniofacial surgery. The present study aimed to determine new
      criteria regarding surgical or observational treatment, especially concerning the
      fracture dislocation. Clinical information on 164 consecutive patients with
      fractures of the frontal sinus, treated at the Department of Craniomaxillofacial
      Surgery of the Medical University of Innsbruck from 2006 to 2010, have been
      evaluated. 23 female (14%) and 141 male (86%) patients suffered mainly from
      traffic (31.7%) and sports accidents (28.0%), followed by work accidents (20.1%),
      violence (3.7%) and accidents at home (3.1%). 51.8% presented an isolated
      fracture of the anterior wall, 47.6% both anterior and posterior wall fracture,
      0.6% an isolated posterior wall fracture. Injury of the nasofrontal duct was
      found in 29.2%, CSF liquorrhoea in 15.9%. In total, 44.5% of the patients
      underwent surgical therapy, 55.5% were treated conservatively by observation.
      Treatment decision depended significantly on concomitant injuries of the
      nasofrontal duct and the presence of rhinoliquorrhoea as well as on the fracture
      dislocation. A new classification of frontal sinus fractures depending on their
      maximum dislocation is proposed. In addition, a treatment algorithm considering
      displacement, liquorrhoea and injury of the nasofrontal duct is presented.

PMID- 24942099
TI  - Photoelectrocatalytic degradation of rhodamine B on TiO2 photonic crystals.
AB  - As the inverse-opal structure facilitates the separation of electron-hole pairs
      and electron transfer, it may generate many radical species with strong oxidation
      capability. When a low bias voltage was applied on the TiO2 electrodes with
      inverse-opal structure, they exhibited more excellent photoelectrochemical
      properties and photoelectrocatalytic activity than TiO2 film under simulated
      solar light irradiation. When different types of active species scavengers were
      added, the different performances of TiO2 photonic crystals in rhodamine B
      degradation showed that besides OH and holes, which were the main active species
      in the photocatalysis, O2(-) played a vital role in the photoelectrocatalytic
      degradation process. Furthermore, the stronger signal of OH-trapping
      photoluminescence and the variation in the concentration of nitroblue tetrazolium
      reflected that more OH and O2(-) could be generated in the photoelectrocatalysis
      than that in the photocatalysis, and O2(-) was partially obtained from the
      cathode surface. At last, the roles active species played in the
      photoelectrocatalytic and photocatalytic processes were compared, and the
      possible degradation mechanisms of TiO2 photonic crystals in
      photoelectrocatalytic and photocatalytic systems were put forward, which could
      provide a good insight into the mechanism of photoelectrocatalytic degradation on
      TiO2 photonic crystals. 

PMID- 24942100
TI  - Diagnosing attention-deficit hyperactivity disorder (ADHD) in children involved
      with child protection services: are current diagnostic guidelines acceptable for
      vulnerable populations?
AB  - Children involved with child protection services (CPS) are diagnosed and treated
      for attention-deficit hyperactivity disorder (ADHD) at higher rates than the
      general population. Children with maltreatment histories are much more likely to
      have other factors contributing to behavioural and attentional regulation
      difficulties that may overlap with or mimic ADHD-like symptoms, including
      language and learning problems, post-traumatic stress disorder, attachment
      difficulties, mood disorders and anxiety disorders. A higher number of children
      in the child welfare system are diagnosed with ADHD and provided with
      psychotropic medications under a group care setting compared with family-based,
      foster care and kinship care settings. However, children's behavioural
      trajectories change over time while in care. A reassessment in the approach to
      ADHD-like symptoms in children exposed to confirmed (or suspected) maltreatment
      (e.g. neglect, abuse) is required. Diagnosis should be conducted within a
      multidisciplinary team and practice guidelines regarding ADHD diagnostic and
      management practices for children in CPS care are warranted both in the USA and
      in Canada. Increased education for caregivers, teachers and child welfare staff
      on the effects of maltreatment and often perplexing relationship with ADHD-like
      symptoms and co-morbid disorders is also necessary. Increased partnerships are
      needed to ensure the mental well-being of children with child protection
      involvement. 

PMID- 24942101
TI  - SERS imaging of cell-surface biomolecules metabolically labeled with
      bioorthogonal Raman reporters.
AB  - Live imaging of biomolecules with high specificity and sensitivity as well as
      minimal perturbation is essential for studying cellular processes. Here, we
      report the development of a bioorthogonal surface-enhanced Raman scattering
      (SERS) imaging approach that exploits small Raman reporters for visualizing cell
      surface biomolecules. The cells were cultured and imaged by SERS microscopy on
      arrays of Raman-enhancing nanoparticles coated on silicon wafers or glass slides.
      The Raman reporters including azides, alkynes, and carbon?deuterium bonds are
      small in size and spectroscopically bioorthogonal (background-free). We
      demonstrated that various cell-surface biomolecules including proteins, glycans,
      and lipids were metabolically incorporated with the corresponding precursors
      bearing a Raman reporter and visualized by SERS microscopy. The coupling of SERS
      microscopy with bioorthogonal Raman reporters expands the capabilities of live
      cell microscopy beyond the modalities of fluorescence and label-free imaging. 

PMID- 24942102
TI  - Spontaneous pneumothorax associated with talc pulmonary granulomatosis after
      cocaine inhalation.
AB  - We report a case of recurrent spontaneous pneumothorax in a patient with cocaine
      abuse through inhalation alone. He underwent thoracoscopic apical lung resection
      with mechanical pleurodesis. Despite the lack of significant radiological
      features of talc induced pulmonary granulomatosis, pathological findings showed
      granulomas with foreign materials suggestive of being talc. Electronic microscopy
      showed that the size of talc particles were <4.0 um and thus small enough to
      reach the alveoli. 

PMID- 24942104
TI  - Safe and successful bone marrow biopsy: an anatomical and CT-based cadaver study.
AB  - Bone marrow biopsy is generally a safe procedure. However, infrequently the
      procedure is associated with serious injuries that are attributed to inadvertent
      needle penetration of the iliac bone's inner cortex. An evidence-based approach
      to needle orientation during iliac crest biopsy does not exist. In our study, the
      posterior to anterior path of the bone marrow needle from the posterior superior
      iliac spine (PSIS) was studied in human cadavers in two orientations: (1)
      perpendicularly to the coronal plane (the perpendicular approach) and (2)
      laterally toward the ipsilateral anterior superior iliac spine (ASIS) (the
      lateral approach). The biopsy needle was deliberately advanced through the inner
      ilial cortex in both approaches. Dissections and imaging studies were done to
      identify the relationship of the penetrating needle to internal structures. Both
      approaches begin with a perpendicular puncture of the outer cortex at the PSIS.
      The perpendicular approach proceeds anteriorly whereas in the lateral approach
      the needle is reoriented toward the ipsilateral ASIS before advancing. The
      lateral approach caused less damage to neurovascular structures and avoided the
      sacroiliac joint compared to the perpendicular approach. This procedure is best
      done in the lateral decubitus position. Proper use of the lateral approach should
      obviate many of the complications reported in the literature.

PMID- 24942105
TI  - Fish intelligence, sentience and ethics.
AB  - Fish are one of the most highly utilised vertebrate taxa by humans; they are
      harvested from wild stocks as part of global fishing industries, grown under
      intensive aquaculture conditions, are the most common pet and are widely used for
      scientific research. But fish are seldom afforded the same level of compassion or
      welfare as warm-blooded vertebrates. Part of the problem is the large gap between
      people's perception of fish intelligence and the scientific reality. This is an
      important issue because public perception guides government policy. The
      perception of an animal's intelligence often drives our decision whether or not
      to include them in our moral circle. From a welfare perspective, most researchers
      would suggest that if an animal is sentient, then it can most likely suffer and
      should therefore be offered some form of formal protection. There has been a
      debate about fish welfare for decades which centres on the question of whether
      they are sentient or conscious. The implications for affording the same level of
      protection to fish as other vertebrates are great, not least because of fishing
      related industries. Here, I review the current state of knowledge of fish
      cognition starting with their sensory perception and moving on to cognition. The
      review reveals that fish perception and cognitive abilities often match or exceed
      other vertebrates. A review of the evidence for pain perception strongly suggests
      that fish experience pain in a manner similar to the rest of the vertebrates.
      Although scientists cannot provide a definitive answer on the level of
      consciousness for any non-human vertebrate, the extensive evidence of fish
      behavioural and cognitive sophistication and pain perception suggests that best
      practice would be to lend fish the same level of protection as any other
      vertebrate. 

PMID- 24942103
TI  - Association of African genetic ancestry with fasting glucose and HbA1c levels in
      non-diabetic individuals: the Boston Area Community Health (BACH) Prediabetes
      Study.
AB  - AIMS/HYPOTHESIS: To test among diabetes-free urban community-dwelling adults the
      hypothesis that the proportion of African genetic ancestry is positively
      associated with glycaemia, after accounting for other continental ancestry
      proportions, BMI and socioeconomic status (SES). METHODS: The Boston Area
      Community Health cohort is a multi-stage 1:1:1 stratified random sample of self
      identified African-American, Hispanic and white adults from three Boston inner
      city areas. We measured 62 ancestry informative markers, fasting glucose (FG),
      HbA1c, BMI and SES (income, education, occupation and insurance status) and
      analysed 1,387 eligible individuals (379 African-American, 411 Hispanic, 597
      white) without clinical or biochemical evidence of diabetes. We used three
      heritage multinomial linear regression models to test the association of FG or
      HbA1c with genetic ancestry proportion adjusted for: (1) age and sex; (2) age,
      sex and BMI; and (3) age, sex, BMI and SES. RESULTS: Mean age- and sex-adjusted
      FG levels were 5.73 and 5.54 mmol/l among those with 100% African or European
      ancestry, respectively. Using per cent European ancestry as the referent, each 1%
      increase in African ancestry proportion was associated with an age- and sex
      adjusted FG increase of 0.0019 mmol/l (p = 0.01). In the BMI- and SES-adjusted
      model the slope was 0.0019 (p = 0.02). Analysis of HbA1c gave similar results.
      CONCLUSIONS/INTERPRETATION: A greater proportion of African genetic ancestry is
      independently associated with higher FG levels in a non-diabetic community-based
      cohort, even accounting for other ancestry proportions, obesity and SES. The
      results suggest that differences between African-Americans and whites in type 2
      diabetes risk may include genetically mediated differences in glucose
      homeostasis.

PMID- 24942106
TI  - Bonobos and orangutans, but not chimpanzees, flexibly plan for the future in a
      token-exchange task.
AB  - Non-human animals, including great apes, have been suggested to share some of the
      skills for planning that humans commonly exhibit. A crucial difference between
      human and non-human planning may relate to the diversity of domains and needs in
      which this skill is expressed. Although great apes can save tools for future use,
      there is little evidence yet that they can also do so in other contexts. To
      investigate this question further, we presented the apes with a planning token
      exchange task that differed from standard tool-use tasks. Additionally, we
      manipulated the future outcome of the task to investigate planning flexibility.
      In the Exchange condition, subjects had to collect, save and transport tokens
      because they would need them 30 min later to exchange them for food with a human,
      i.e., "bring-back" response. In the Release condition, the collection and
      transport of tokens were not needed as no exchange took place after 30 min. Out
      of 13 subjects, eight solved the task at least once in the Exchange condition,
      with chimpanzees appearing less successful than the other species. Importantly,
      three individuals showed a clear differential response between conditions by
      producing more "bring-back" responses in the Exchange than in the Release
      conditions. Those bonobo and orangutan individuals hence adapted their planning
      behavior according to changing needs (i.e., they brought tokens back
      significantly more often when they would need them). Bonobos and orangutans,
      unlike chimpanzees, planned outside the context of tool-use, thus challenging the
      idea that planning in these species is purely domain-specific. 

PMID- 24942107
TI  - Interpretation of human pointing by African elephants: generalisation and
      rationality.
AB  - Factors influencing the abilities of different animals to use cooperative social
      cues from humans are still unclear, in spite of long-standing interest in the
      topic. One of the few species that have been found successful at using human
      pointing is the African elephant (Loxodonta africana); despite few opportunities
      for learning about pointing, elephants follow a pointing gesture in an object
      choice task, even when the pointing signal and experimenter's body position are
      in conflict, and when the gesture itself is visually subtle. Here, we show that
      the success of captive African elephants at using human pointing is not
      restricted to situations where the pointing signal is sustained until the time of
      choice: elephants followed human pointing even when the pointing gesture was
      withdrawn before they had responded to it. Furthermore, elephants rapidly
      generalised their response to a type of social cue they were unlikely to have
      seen before: pointing with the foot. However, unlike young children, they showed
      no sign of evaluating the 'rationality' of this novel pointing gesture according
      to its visual context: that is, whether the experimenter's hands were occupied or
      not. 

PMID- 24942108
TI  - Depth perception: cuttlefish (Sepia officinalis) respond to visual texture
      density gradients.
AB  - Studies concerning the perceptual processes of animals are not only interesting,
      but are fundamental to the understanding of other developments in information
      processing among non-humans. Carefully used visual illusions have been proven to
      be an informative tool for understanding visual perception. In this behavioral
      study, we demonstrate that cuttlefish are responsive to visual cues involving
      texture gradients. Specifically, 12 out of 14 animals avoided swimming over a
      solid surface with a gradient picture that to humans resembles an illusionary
      crevasse, while only 5 out of 14 avoided a non-illusionary texture. Since texture
      gradients are well-known cues for depth perception in vertebrates, we suggest
      that these cephalopods were responding to the depth illusion created by the
      texture density gradient. Density gradients and relative densities are key
      features in distance perception in vertebrates. Our results suggest that they are
      fundamental features of vision in general, appearing also in cephalopods. 

PMID- 24942110
TI  - Cannabis regulation: the need to develop guidelines on use.

PMID- 24942109
TI  - Identification of GH10 xylanases in strains 2 and Mz5 of Pseudobutyrivibrio
      xylanivorans.
AB  - Genes encoding glycosyl hydrolase family 11 (GH11) xylanases and xylanases have
      been identified from Pseudobutyrivibrio xylanivorans. In contrast, little is
      known about the diversity and distribution of the GH10 xylanase in strains of P.
      xylanivorans. Xylanase and associated activities of P. xylanivorans have been
      characterized in detail in the type strain, Mz5. The aim of the present study was
      to identify GH10 xylanase genes in strains 2 and Mz5 of P. xylanivorans. In
      addition, we evaluated degradation and utilization of xylan by P. xylanivorans 2
      isolated from rumen of Creole goats. After a 12-h culture, P. xylanivorans 2 was
      able to utilize up to 53% of the total pentose content present in birchwood xylan
      (BWX) and to utilize up to 62% of a ethanol-acetic acid-soluble fraction prepared
      from BWX. This is the first report describing the presence of GH10 xylanase
      encoding genes in P. xylanivorans. Strain 2 and Mz5 contained xylanases which
      were related to GH10 xylanase of Butyrivibrio sp. Identifying xylanase-encoding
      genes and activity of these enzymes are a step toward understanding possible
      functional role of P. xylanivorans in the rumen ecosystem and contribute to
      providing an improved choice of enzymes for improving fiber digestion in ruminant
      animals, agricultural biomass utilization for biofuel production, and other
      industries.

PMID- 24942111
TI  - Knowledge cannot explain the developmental growth of working memory capacity.
AB  - According to some views of cognitive growth, the development of working memory
      capacity can account for increases in the complexity of cognition. It has been
      difficult to ascertain, though, that there actually is developmental growth in
      capacity that cannot be attributed to other developing factors. Here we assess
      the role of item familiarity. We document developmental increases in working
      memory for visual arrays of English letters versus unfamiliar characters.
      Although letter knowledge played a special role in development between the ages
      of 6 and 8 years, children with adequate letter knowledge showed practically the
      same developmental growth in normalized functions for letters and unfamiliar
      characters. The results contribute to a growing body of evidence that the
      developmental improvement in working memory does not wholly stem from supporting
      processes such as encoding, mnemonic strategies, and knowledge. A video abstract
      is available at: https://www.youtube.com/watch?v=LJdqErLR2Hs&feature=youtu.be. 

PMID- 24942112
TI  - An application of a Hill-based response surface model for a drug combination
      experiment on lung cancer.
AB  - Combination chemotherapy with multiple drugs has been widely applied to cancer
      treatment owing to enhanced efficacy and reduced drug resistance. For drug
      combination experiment analysis, response surface modeling has been commonly
      adopted. In this paper, we introduce a Hill-based global response surface model
      and provide an application of the model to a 512-run drug combination experiment
      with three chemicals, namely AG490, U0126, and indirubin-3  ' -monoxime (I-3-M),
      on lung cancer cells. The results demonstrate generally improved goodness of fit
      of our model from the traditional polynomial model, as well as the original Hill
      model on the basis of fixed-ratio drug combinations. We identify different dose
      effect patterns between normal and cancer cells on the basis of our model, which
      indicates the potential effectiveness of the drug combination in cancer
      treatment. Meanwhile, drug interactions are analyzed both qualitatively and
      quantitatively. The distinct interaction patterns between U0126 and I-3-M on two
      types of cells uncovered by the model could be a further indicator of the
      efficacy of the drug combination.

PMID- 24942113
TI  - Vasomotor effects of acetylcholine, bradykinin, noradrenaline, 5
      hydroxytryptamine, histamine and angiotensin II on the mouse basilar artery.
AB  - We investigated the responsiveness of the mouse basilar artery to acetylcholine
      (ACh), bradykinin (BK), noradrenaline (NA), 5-hydroxytryptamine (5-HT), histamine
      (His) and angiotensin (Ang) II in order to characterize the related receptor
      subtypes in vitro. ACh and BK induced endothelium-dependent relaxation of
      precontracted arteries with U-46619 (a thromboxane A2 analogue). Atropine (a non
      selective muscarinic receptor antagonist) and Nomega-nitro-L-arginine (a NO
      synthase inhibitor, L-NNA) shifted the concentration-response curve for ACh to
      the right, whereas pirenzepine, methoctramine and pFHHSiD (muscarinic M1, M2 and
      M3 antagonists, respectively) had no significant effect. L-NNA and HOE140 (a B2
      antagonist) shifted the concentration-response curve for BK to the right, whereas
      des-Arg(9)-[Leu(8)]-BK (a B1 antagonist) and indomethacin (a cyclooxygenase
      inhibitor) had no significant effect. NA failed to produce any vasomotor action.
      His and Ang II induced concentration-dependent contraction. Diphenhydramine (a H1
      antagonist) shifted the concentration-response curve for His to the right,
      whereas cimetidine (a H2 antagonist) had no significant effect. Losartan (an AT1
      antagonist) shifted the concentration-response curve for Ang II to the right,
      whereas PD123319 (an AT2 antagonist) had no significant effect. These results
      suggest that the H1 and AT1 receptor subtypes might play an important role in
      arterial contraction, whereas muscarinic receptor subtypes apart from M1, M2 and
      M3, and B2 receptors on the endothelium, might modify these contractions to
      relaxations. 

PMID- 24942114
TI  - Zygomatic sialolithiasis diagnosed with computed tomography in a dog.
AB  - A 10-year-old castrated Shih-Tzu male dog was referred for examination of acute
      right exophthalmos, protrusion of the third eyelid and soft tissue swelling
      ventral to the globe. Ultrasonography revealed echogenic fluid around the right
      globe. Computed tomography (CT) showed an enlarged right zygomatic salivary gland
      compared with the left zygomatic gland and an amorphous cystic mass ventral to
      the right globe. Hyperdense material, which we suspected to be a sialolith, was
      identified in the right zygomatic gland. The zygomatic gland and the cystic
      lesion were removed, and a zygomatic sialocele with sialolith and ductal
      obstruction were found by histopathological examination. CT was a useful
      diagnostic tool for zygomatic sialolithiasis. 

PMID- 24942115
TI  - Effects of exposure to male goat hair extracts on luteinizing hormone secretion
      and neuronal activation in seasonally anestrous ewes.
AB  - In sheep and goats, exposure of seasonally anestrous females to males or their
      fleece/hair activates the gonadotropin-releasing hormone (GnRH) pulse generator
      leading to pulsatile luteinizing hormone (LH) secretion. Pheromones emitted by
      sexually mature males are thought to play a prominent role in this male effect.
      In the present study, we first aimed to clarify whether the male goat pheromone
      is effective in ewes. Seasonally anestrous St. Croix ewes were exposed to hair
      extracts derived from either intact or castrated (control) male Shiba goats. The
      male goat-hair extract significantly increased LH secretion compared to the
      control, suggesting that an interspecies action of the male pheromone occurs
      between sheep and goats. Using the male goat-hair extract as the pheromone
      source, we then aimed to clarify the neural pathway involved in the signal
      transduction of the male pheromone. Ewes were exposed to either the goat-hair
      extract or the control and sacrificed 2 hr after the exposure. Expression of c
      Fos, a marker of neuronal activation, was immunohistochemically examined. The
      male goat-hair extract significantly increased the c-Fos expression compared to
      the control in regions of the vomeronasal system, such as the accessory olfactory
      bulb and medial amygdala, and the arcuate nucleus. The main olfactory bulb did
      not exhibit any significant increase in the c-Fos expression by the male goat
      hair extract. This result suggests that the neural signal of the male pheromone
      is conveyed to the GnRH pulse generator through the activated regions in ewes. 

PMID- 24942116
TI  - [Quo vadis laser technology? An update on application to the cornea].

PMID- 24942117
TI  - [Importance of wavelength for ultrashort laser pulses in healthy and pathological
      corneas].
AB  - BACKGROUND: A study on the role of laser wavelength in keratoplasty assisted by
      ultrashort pulse lasers is presented. MATERIAL AND METHODS: This article gives a
      summary of the principal physical mechanisms contributing to the transparency of
      healthy corneas and presents transparency measurements as well as laboratory
      experiments on tissue with lasers at different wavelengths. RESULTS: The
      transparency of a healthy cornea is strongly related to its regular structure at
      micrometer and nanometer length scales. Many indications for keratoplasty are
      associated with a perturbation of this structure and therefore with a sometimes
      strongly reduced tissue transparency. This explains the often unsatisfactory
      results obtained when using ultrashort pulse lasers for the procedure.
      Theoretical considerations and laboratory experiments show that the light
      scattering processes responsible for the loss in laser beam quality depend
      strongly on wavelength and the use of wavelengths longer than those presently
      used allows these processes to be almost completely eliminated. The use of a
      spectral transparency window close to 1.65 um is suggested. CONCLUSION: The use
      of laser wavelengths close to 1.65 um represents an interesting alternative for
      the improvement of keratoplasty assisted by ultrashort pulse lasers.

PMID- 24942118
TI  - [Perspectives of laser-assisted keratoplasty: current overview and first
      preliminary results with the picosecond infrared laser (lambda = 3 um)].
AB  - BACKGROUND: This article provides a review of the current state of laser-assisted
      keratoplasty and describes a first proof of concept study to test the feasibility
      of a new mid-infrared (MIR) picosecond laser to perform applanation-free corneal
      trephination. METHODS: The procedure is based on a specially adapted laser system
      (PIRL-HP2-1064 OPA-3000, Attodyne, Canada) which works with a wavelength of 3,000
      +/- 90 nm, a pulse duration of 300 ps and a repetition rate of 1 kHz. The
      picosecond infrared laser (PIRL) beam is delivered to the sample by a custom-made
      optics system with an implemented scanning mechanism. Corneal specimens were
      mounted on an artificial anterior chamber and subsequent trephination was
      performed with the PIRL under stable intraocular pressure conditions. RESULTS: A
      defined corneal ablation pattern, e.g. circular, linear, rectangular or disc
      shaped, can be selected and its specific dimensions are defined by the user.
      Circular and linear ablation patterns were employed for the incisions in this
      study. Linear and circular penetrating PIRL incisions were examined by
      macroscopic inspection, histology, confocal microscopy and environmental scanning
      electron microscopy (ESEM) for characterization of the incisional quality. Using
      PIRL reproducible and stable incisions could be made in human and porcine corneal
      samples with minimal damage to the surrounding tissue. CONCLUSION: The PIRL laser
      radiation in the mid-infrared spectrum with a wavelength of 3 um is exactly tuned
      to one of the dominant vibrational excitation bands of the water molecule, serves
      as an effective tool for applanation-free corneal incision and might broaden the
      armamentarium of corneal transplant surgery.

PMID- 24942119
TI  - [Alternatives to femtosecond laser technology: subnanosecond UV pulse and ring
      foci for creation of LASIK flaps].
AB  - BACKGROUND: In refractive corneal surgery femtosecond (fs) lasers are used for
      creating LASIK flaps, dissecting lenticules and for astigmatism correction by
      limbal incisions. OBJECTIVES: Femtosecond laser systems are complex and expensive
      and cutting precision is compromised by the large focal length associated with
      the commonly used infrared (IR) wavelengths. Based on investigations of the
      cutting dynamics, novel approaches for corneal dissection using ultraviolet A
      (UVA) picosecond (ps) pulses and ring foci from vortex beams are presented.
      METHODS: Laser-induced bubble formation in corneal stroma was investigated by
      high-speed photography at 1-50 million frames/s. Using Gaussian and vortex beams
      of UVA pulses with durations between 200 and 850 ps the laser energy needed for
      easy removal of flaps created in porcine corneas was determined and the quality
      of the cuts by scanning electron microscopy was documented. Cutting parameters
      for 850 ps are reported also for rabbit eyes. The UV-induced and mechanical
      stress were evaluated for Gaussian and vortex beams. RESULTS: The results show
      that UVA picosecond lasers provide better cutting precision than IR femtosecond
      lasers, with similar processing times. Cutting energy decreases by >50 % when the
      laser pulse duration is reduced to 200 ps. Vortex beams produce a short, donut
      shaped focus allowing efficient and precise dissection along the corneal lamellae
      which results in a dramatic reduction of the absorbed energy needed for cutting
      and of mechanical side effects as well as in less bubble formation in the cutting
      plane. CONCLUSION: A combination of novel approaches for corneal dissection
      provides the option to replace femtosecond lasers by compact UVA microchip laser
      technology. Ring foci are also of interest for femtosecond laser surgery,
      especially for improved lenticule excision.

PMID- 24942120
TI  - [Innovations in refractive laser surgery 2014].
AB  - BACKGROUND: Within less than 30 years refractive laser surgery has been developed
      from an experimental technique to one of the most frequently applied procedures
      in ophthalmology worldwide. RESULTS: Regarding the success rate of refractive
      results, myopia correction has reached a level (95% within +/- 0.5 D) that is
      comparable to manifest refraction so that there is not much room for improvement.
      The most recently developed technique is femtosecond laser lenticule extraction
      which was introduced in 2007 in Germany. Early clinical results were very
      promising but the awaited bilateral comparative studies are still lacking.
      Although new laser types that will be able to provide improved profiles are on
      the horizon, the problem of reoperations has not yet been solved. Topography
      guided ablation is notoriously plagued by undercorrection so that topography
      guided treatment is planned as a two step-procedure. The reason for the
      undercorrection is the leveling effect of the epithelium. PERSPECTIVES: The
      evolution of refractive surgery has slowed down during the last years, however,
      some important innovations are at the advent.

PMID- 24942121
TI  - [Swelling in the left medial angle of the eyelid in a 42-year-old woman].

PMID- 24942123
TI  - [Intraocular pressure and glaucomatous damage].

PMID- 24942122
TI  - [Porous orbital implants].
AB  - Since the introduction of the first coralline hydroxyapatite porous orbital
      implant as eye replacement in the early 1980s, numerous other modified porous
      implants have been developed. Due to the different design of the existing studies
      concerning long-term safety with, in some cases, relatively short follow-up, a
      comparison is difficult and none of the implant types can be clearly identified
      as being superior. Factors affecting the exposure rate of the implant seem to be
      the implant coating, the surgical technique and the condition of the patient's
      tissue at the beginning of surgery. 

PMID- 24942124
TI  - [Essential aspects of ophthalmological expert assessment in private accident
      insurance].
AB  - Commissions for an expert assessment place basically high demands on commissioned
      eye specialists because this activity differs from the normal routine field of
      work. In addition to assessing objective symptoms and subjective symptomatics in
      a special analytical manner, eye specialists are expected to have knowledge of
      basic legal terminology, such as proximate cause, evidence and evidential value.
      Only under these prerequisites can an ophthalmologist fulfill the function of an
      expert with a high level of quality and adequately adjust the special medical
      ophthalmological expertise to the requirements of the predominantly legally based
      clients commissioning the report and oriented to the appropriate valid legal
      norms. Particularly common difficulties associated with making an
      ophthalmological expert report for private accident insurance, e.g. determination
      of the reduction in functional quality, consideration of partial causality and
      assessment of diplopia are discussed. 

PMID- 24942125
TI  - Beyond prevalence: an explanatory approach to reframing child maltreatment in the
      United Kingdom: the most prevalent form of maltreatment, child neglect, gets the
      least attention from the public and policymakers.

PMID- 24942126
TI  - Portrayals of child abuse scandals in the media in Australia and England: impacts
      on practice, policy, and systems: most media coverage distorts the public
      understandings of the nature of child maltreatment.

PMID- 24942127
TI  - How do Australian print media representations of child abuse and neglect inform
      the public and system reform?: stories place undue emphasis on social control
      measures and too little emphasis on social care responses.

PMID- 24942129
TI  - Acute cerebellitis in varicella: a ten year case series and systematic review of
      the literature.
AB  - BACKGROUND: Acute cerebellitis (AC) is the most common neurological complication
      of varicella. Nevertheless, it has been scarcely studied. The objective of this
      study were to asses the occurrence of AC among children hospitalized for
      varicella and to analyze its specific clinical picture and outcome. METHODS: We
      retrospectively reviewed the medical records of children admitted to the hospital
      for varicella between 1st October 2003 and 1st June 2013 and we compared our
      results with literature. Children were all unvaccinated for varicella. RESULTS:
      In our case series, AC was found out in 48 out of 457 patients (10.5%). The
      highest frequency of AC was observed in children from 1 to 5 years of age
      (60.9%). The most characteristic symptom of AC was a broad-based gait disturbance
      that progressed gradually over the course of a few days (95.8%). Other common
      symptoms included slurred speech (37.5%), vomiting (31.25%), headache (29.16%),
      dysmetry (25%) and tremor (22.91%). After a long hospitalization (median of 11
      days), all but one children were dismissed without invalidating sequelae.
      CONCLUSIONS: Data from this study may help to better address the problem of
      varicella cerebellar complications in hospitalized children and to monitor
      changes over time caused by an increase in vaccination coverage.

PMID- 24942128
TI  - Quantifying the impact of exogenous abscisic acid and gibberellins on pre
      maturity alpha-amylase formation in developing wheat grains.
AB  - To study the role of abscisic acid (ABA) and gibberellins (GA) in pre-maturity
      alpha-amylase (PMA) formation in developing wheat grain, two glasshouse
      experiments were conducted under controlled conditions in the highly PMA
      susceptible genotype Rialto. The first, determined the relative efficacy of
      applying hormone solutions by injection into the peduncle compared to direct
      application to the intact grain. The second, examined the effects of each
      hormone, applied by either method, at mid-grain development on PMA in mature
      grains. In the first experiment, tritiated ABA ((3)H-ABA) and gibberellic acid
      ((3)H-GA3) were diluted with unlabelled ABA (100 uM) and GA3 (50 uM),
      respectively, and applied at mid-grain development using both methods. Spikes
      were harvested after 24, 48 and 72 h from application, and hormone taken up by
      grains was determined. After 72 h, the uptake per grain in terms of hormones
      applied was approximately 13% for ABA and 8% for GA3 when applied onto the
      grains, and approximately 17% for ABA and 5% for GA3 when applied by injection.
      In the second experiment, applied ABA reduced, whereas applied GA3 increased
      alpha-amylase activity. This confirmed that exogenously applied ABA and GA were
      absorbed in sufficient amounts to alter grain metabolism and impact on PMA.

PMID- 24942130
TI  - PDE4D inhibitors: a potential strategy for the treatment of memory impairment?

PMID- 24942131
TI  - Living in shear: platelets protect cancer cells from shear induced damage.
AB  - Pharmacologically and genetically induced thrombocytopenia is associated with
      decreased metastasis, highlighting the importance of platelets in the bloodborne
      dissemination of cancer cells. It is frequently suggested that platelets support
      metastasis, in part, by protecting cancer cells from shear stress, a
      biomechanical force generated by blood flow. However, there is currently no
      evidence to support this hypothesis. To address this, we investigated the effect
      of shear stress on A2780 ovarian cancer cells in the presence and absence of
      platelets. Using a cone and plate viscometer, suspensions of A2780 cells with and
      without platelets were exposed to shear rates representing venous (200 s(-1)) and
      arterial (1,500 s(-1)) blood flow. Lactate dehydrogenase (LDH) release was used
      to quantify shear induced membrane damage. Both venous and arterial shear rates
      induced the release of LDH from A2780 cells, demonstrating their susceptibility
      to shear forces. In contrast, platelets released minimal levels of LDH in
      response to similar conditions. In the presence of platelets, there was a
      significant decrease in LDH release by A2780 cells under shear conditions,
      suggesting that platelets can confer protection against shear induced damage. The
      disruption of platelet-cancer cell interactions could increase the shear stress
      induced destruction of cancer cells in vivo. 

PMID- 24942133
TI  - The influence of life events on physical activity patterns of Dutch older adults:
      a life history method.
AB  - OBJECTIVE: Physical activity (PA) can improve well-being and health during older
      age. This study explored how life events influence PA patterns of older adults.
      DESIGN: Seventeen interviews with older adults were conducted using a life
      history method. PA patterns during the life course were identified, including
      information on when, how and why changes in PA occurred. RESULTS: Four different
      response patterns that affect PA patterns after life events (e.g. death of
      partner) were discerned as follows: 'I want to be physically active, but there
      are too many barriers', 'I have reached a point in my life where I do not have to
      be so active any more', 'I need to exercise now if I want to live the life I
      want' and 'I have always been active and cannot do without PA'. Which response
      pattern an older adult held was strongly related to PA development during earlier
      life (physical capital), and present and future self-conceptions. CONCLUSIONS:
      When developing interventions to enhance PA in older age, it is important to take
      into account the diversity of views on PA, based on physical capital and current
      and future self-conceptions. The life history method appeared valuable, providing
      a thorough understanding of changes in PA patterns.

PMID- 24942132
TI  - Transverse vaginal septae: management and long-term outcomes.
AB  - OBJECTIVE: To examine the management and long-term outcomes of transverse vaginal
      septae. DESIGN: Observational study with cross-sectional and retrospective arms.
      SETTING: Tertiary referral centre specialising in Mullerian anomalies.
      POPULATION: Forty-six girls and women with a transverse vaginal septum. METHODS:
      Data from medical records of all cases (1998-2013) of transverse vaginal septae
      were collected and reviewed. Patients over 16 years of age also completed a
      questionnaire. MAIN OUTCOME MEASURES: Presentation, examination findings,
      investigations, surgery, and long-term reproductive outcomes. RESULTS: The septae
      in the study were described as follows: 61% (95% CI 0.46-0.74) were imperforate,
      and presented with obstructed menstruation; 39% (95% CI 0.26-0.54) were
      perforate, and presented with a variety of concerns; 72% (95% CI 0.57-0.83) were
      low, 22% (95% CI 0.12-0.36) were mid-vaginal, and 6% (95% CI 0.02-0.18) were
      high; 33% were managed via an abdominoperineal approach, 59% were managed via a
      vaginal approach, and 6% had laparoscopic resection (one patient did not have
      surgery); 11% (95% CI 0.05-0.23) of patients presented with reobstruction, all
      following abdominoperineal vaginoplasty; 7% presented with vaginal stenosis, two
      following vaginal resection and one following the abdominoperineal approach; 61%
      of questionnaires were returned. These results showed that 22/23 patients were
      menstruating and one had a hysterectomy, 74% had been sexually active, 35% had
      dyspareunia, and 36% complained of dysmenorrhoea. There were seven pregnancies,
      with one termination and six live births, all following the vaginal excision of a
      transverse vaginal septum. CONCLUSIONS: Transverse vaginal septae resected
      vaginally or laparoscopically have low complication rates and good long-term
      outcomes. Complex septae require more extensive surgery, with an increased risk
      of complications.

PMID- 24942134
TI  - Responsive 3D microstructures from virus building blocks.
AB  - Fabrication of 3D biological structures reveals dynamic response to external
      stimuli. A liquid-crystalline bridge extrusion technique is used to generate 3D
      structures allowing the capture of Rayleigh-like instabilities, facilitating
      customization of smooth, helical, or undulating periodic surface textures. By
      integrating intrinsic biochemical functionality and synthetic components into
      controlled structures, this strategy offers a new form of adaptable materials. 

PMID- 24942136
TI  - Selective axonal and glial distribution of monoacylglycerol lipase
      immunoreactivity in the superficial spinal dorsal horn of rodents.
AB  - The importance of 2-AG-mediated endogenous cannabinoid signaling in spinal pain
      control has recently been well substantiated. Although the degradation of 2-AG
      seems to be essential in cannabinoid-mediated spinal nociceptive information
      processing, no experimental data are available about the cellular distribution of
      monoacylglycerol lipase (MGL), the main degrading enzyme of 2-AG in the spinal
      dorsal horn. Thus, here we investigated the cellular distribution of MGL in
      laminae I-II of the spinal gray matter with immunocytochemical methods and
      revealed an abundant immunoreactivity for MGL in the rodent superficial spinal
      dorsal horn. We addressed the co-localization of MGL with markers of peptidergic
      and non-peptidergic primary afferents, axon terminals of putative glutamatergic
      and GABAergic spinal neurons, as well as astrocytic and microglial profiles, and
      we found that nearly 17 % of the peptidergic (immunoreactive for CGRP), a bit
      more than 10 % of the axon terminals of putative glutamatergic spinal neurons
      (immunoreactive for VGLUT2), and approximately 20 % of the astrocytic
      (immunoreactive for GFAP) profiles were immunolabeled for MGL. On the other hand,
      however, axon terminals of non-peptidergic (binding isolectin-B4) nociceptive
      primary afferents and putative inhibitory spinal neurons (immunoreactive for
      VGAT) as well as microglial (immunoreactive for CD11b) profiles showed negligible
      immunostaining for MGL. The results suggest that only nociceptive inputs arriving
      through a population of CGRP immunoreactive fibers are modulated by the spinal
      DGLalpha-MGL pathway. We also postulate that the DGLalpha-MGL signaling pathway
      may modulate spinal excitatory but not inhibitory neural circuits.

PMID- 24942137
TI  - Phosphorylation of S845 GluA1 AMPA receptors modulates spatial memory and
      structural plasticity in the ventral striatum.
AB  - The function of AMPA receptors phosphorylation in synaptic plasticity has been
      dissected in many in vitro models but its role and dynamics on experience
      dependent plasticity are still unclear. Here we studied the effects of AMPA
      receptor manipulations in the ventral striatum, where glutamatergic transmission
      is known to mediate spatial memory. We first demonstrate that intra-ventral
      striatal administrations of the AMPA receptors blocker, NBQX, dose dependently
      impair performance in the Morris water maze. We also report that spatial learning
      induced a time-limited increase in GluA1 phosphorylation in this same brain
      region. Finally, through focal, time-controlled ventral striatal administrations
      of an RNA aptamer interfering with GluA1-S845 phosphorylation, we demonstrate
      that phosphorylation at this site is a necessary requirement for spatial memory
      formation and for the synaptic remodeling underlying it. These results suggest
      that modulation of AMPA receptors by S845 phosphorylation could act as an
      essential starting signal leading to long-term stabilization of spatial memories.

PMID- 24942135
TI  - Eye position modulates retinotopic responses in early visual areas: a bias for
      the straight-ahead direction.
AB  - Even though the eyes constantly change position, the location of a stimulus can
      be accurately represented by a population of neurons with retinotopic receptive
      fields modulated by eye position gain fields. Recent electrophysiological
      studies, however, indicate that eye position gain fields may serve an additional
      function since they have a non-uniform spatial distribution that increases the
      neural response to stimuli in the straight-ahead direction. We used functional
      magnetic resonance imaging and a wide-field stimulus display to determine whether
      gaze modulations in early human visual cortex enhance the blood-oxygenation-level
      dependent (BOLD) response to stimuli that are straight-ahead. Subjects viewed
      rotating polar angle wedge stimuli centered straight-ahead or vertically
      displaced by +/- 20 degrees  eccentricity. Gaze position did not affect the
      topography of polar phase-angle maps, confirming that coding was retinotopic, but
      did affect the amplitude of the BOLD response, consistent with a gain field. In
      agreement with recent electrophysiological studies, BOLD responses in V1 and V2
      to a wedge stimulus at a fixed retinal locus decreased when the wedge location in
      head-centered coordinates was farther from the straight-ahead direction. We
      conclude that stimulus-evoked BOLD signals are modulated by a systematic, non
      uniform distribution of eye-position gain fields.

PMID- 24942139
TI  - Maternal patterns of marijuana use and early sexual behavior in offspring of
      teenage mothers.
AB  - Teenage mothers use marijuana more frequently than older mothers, and marijuana
      use may predict HIV risk behavior in offspring. Our goals were to (1) describe
      trajectories of marijuana use in teenage mothers and (2) determine if these
      trajectories were associated with early sexual behavior in their offspring.
      Pregnant adolescents (12-18 years) were recruited at a prenatal clinic and
      interviewed during pregnancy, at delivery, and during follow-up visits when
      offspring were 6, 10, 14 and 16 years old. At 16 years, 332 women (71 % Black, 29
      % White) and their offspring were assessed. Mothers were asked about their
      marijuana use at each time point. Offspring reported on their sexual behavior at
      age 14. Trajectory analyses using growth mixture models revealed four maternal
      patterns of marijuana use: no use, only at the 6 year follow-up, quit by the 16
      year follow-up, and used across most of the time points. The children of chronic
      users were more likely to have early sex. The maternal marijuana trajectory group
      variable remained a statistically significant predictor in multivariate models
      controlling for race, gender, socioeconomic status, child pubertal timing, child
      externalizing behavior problems, and child marijuana use. These findings suggest
      that a minority of teenage mothers continue to use marijuana over time. Chronic
      maternal marijuana use across a decade was associated with early sex in offspring
      (oral or vaginal sex by age 14). Early sexual behavior places these children at
      significantly higher risk of teenage pregnancy and HIV risk behaviors.

PMID- 24942140
TI  - Differential associations of dopamine-related polymorphisms with discrete
      components of reaction time variability: relevance for attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Reaction time variability (RTV) is considered a valid endophenotype
      of attention deficit/hyperactivity disorder (ADHD). It is also often used to
      examine the efficacy of drug treatment or individual patients' treatment
      responses and has been furthermore suggested to significantly reduce the
      potential number of false-positive diagnoses. Among the most commonly
      investigated candidate genes for ADHD are DRD2, SLC6A3 (DAT), COMT and MAOA.
      Genetic associations have, however, proven inconclusive or inconsistent. METHODS:
      Due to the complexity of dopaminergic neurotransmission in the two distinct
      prosencephalic dopamine pathways, we examined whether the effects of dopamine
      related candidate polymorphisms in the genes DRD2, SLC6A3, COMT and MAOA may be
      differentially associated with discrete subcomponents of RTV, rather than global
      RTV. A total of 260 healthy volunteers were genotyped for the aforementioned
      polymorphisms and performed a reaction time paradigm able to distinguish between
      sensory and motor reaction time. RESULTS: We found that functional polymorphisms
      in the genes encoding for dopamine-catabolizing enzymes (i.e. COMT and MAOA) are
      associated with motor RTV but not with sensory RTV, whereas vice versa the gene
      DRD2 influences sensory but not motor RTV. No significant associations for the
      gene SLC6A3 (DAT) were found. CONCLUSIONS: Our results give new insight into the
      inconsistent state of the literature regarding genetic associations of RTV and
      clearly show that the examination of subcomponents thereof explains far more
      variance compared to global RTV. This could be of great relevance to the use of
      RTV in basic research, clinical diagnostics and pharmacological studies examining
      the efficacy of novel drug treatments.

PMID- 24942138
TI  - Factors associated with bed-sharing for African American and White mothers in
      Wisconsin.
AB  - Mother-infant bed-sharing has been associated with a higher risk of sleep-related
      infant deaths, which affects African Americans at a disproportionately higher
      rate. Although "separate but proximate sleep surfaces" for infants has been
      recommended since 2005, bed-sharing remains a common practice, especially among
      African Americans. This study examined factors associated with bed-sharing among
      African American and White mothers. Separate logistic regression models were
      constructed for African American and White respondents to the 2007-2010 Wisconsin
      Pregnancy Risk Assessment and Monitoring System. The sample consisted of 806
      African Americans and 1,680 Whites (N = 2,486). A significantly larger proportion
      of African Americans (70.6 %) reported bed-sharing than Whites (53.4 %). For both
      races, partner-related stress was significantly associated with bed-sharing; no
      significant differences were found between the two racial groups. For African
      Americans, partner stress (OR 1.8: 1.2-2.6) and maternal education of 13-15 years
      (OR 2.0: 1.2-3.4) or >=16 years (OR 2.7: 1.1-6.3) was associated with increased
      odds of bed-sharing. For Whites, partner stress (OR 1.3: 1-1.8), breastfeeding
      (OR 2.5: 1.9-3.1), income of $35,000-$49,999 (OR 1.6: 1.2-2.3), being unmarried
      (OR 1.5: 1.1-2.2), needing money for food (OR 1.6: 1.1-2.3), and non-supine sleep
      (OR 1.8: 1.2-2.6) were associated with increased odds of bed-sharing. Differences
      were found in bed-sharing factors between racial groups which suggests a need for
      culturally-relevant, tailored safe infant sleep interventions. Providers should
      ask families about their infant's sleeping environment and address safety issues
      within that environment. More research is needed on the context and reasons for
      bed-sharing. 

PMID- 24942141
TI  - Evaluation of recovery and quality of sexual activity in women during postpartum
      in relation to the different mode of delivery: a retrospective analysis.
AB  - AIM: Aim of the study was to assess the recovery and quality of sexual activity
      of women during postpartum, in relation to delivery. METHODS: We recruited 200
      women at 8 weeks after delivery. For each patient we recorded mode of delivery,
      age, body mass index (BMI), parity and test Female Sexual Function Index (FSFI)
      score. RESULTS: Sixty-four women (32%) had spontaneous deliveries without
      episiotomy, 48 (24%) had it with episiotomy, 88 (44%) had caesarean sections. The
      analysis of variance (ANOVA) test showed no significant differences among the 3
      groups for age, BMI, parity. The test FSFI evidenced 68 cases (34%) of Regular
      Female Sexual Function (RFSF) and 132 (66%) of Female Sexual Dysfunction (FSD).
      The ANOVA test showed significant differences among the 3 groups in RFSF (F [2,
      14]=8.075, P=0.005), but not in FSD (F [2, 30]=2.646, P=0.087). In RFSF, FSFI
      score was higher in women who had vaginal delivery with episiotomy compared with
      the other two groups. Conversely, in FSD (both with or without resumed sexual
      activity at 8 weeks postpartum) we evidenced that patients who had vaginal
      delivery with episiotomy showed lower FSFI score than the other two groups, with
      a decrease in lubrication, orgasm and satisfaction scores. Furthermore, we
      observed that most of the RFSF patients had a job and breastfed. CONCLUSION: Our
      results did not evidence a direct and significant correlation between mode of
      delivery and onset of female postpartum sexual dysfunction, even if FSD patients
      who underwent episiotomy during delivery markedly showed low FSFI scores.

PMID- 24942143
TI  - Commentary: The hidden and not so hidden benefits of work: identity, income and
      interaction.

PMID- 24942142
TI  - Job loss, wealth and depression during the Great Recession in the USA and Europe.
AB  - AIM: To examine whether late-career job loss increased depression among older
      workers approaching retirement in the USA and Europe. METHODS: Longitudinal data
      came from the Health and Retirement Survey and the Survey of Health, Ageing, and
      Retirement in Europe. Workers aged 50 to 64 years in 13 European countries and
      the USA were assessed biennially from 2006 to 2010. Individual fixed effects
      models were used to test the effect of job loss on depressive symptoms,
      controlling for age, sex, physical health, initial wealth and socio-demographic
      factors. RESULTS: Job loss was associated with a 4.78% [95% confidence interval
      (CI): 0.823% to 8.74%] increase in depressive symptoms in the USA compared with a
      3.35% (95% CI: 0.486% to 6.22%) increase in Europe. Job loss due to a worker's
      unexpected firm closure increased depression scores in both the USA (beta=28.2%,
      95% CI: 8.55% to 47.8%) and Europe (beta=7.50%, 95% CI: 1.25% to 13.70%), but
      pooled models suggested significantly stronger effects for US workers (P<0.001).
      American workers who were poorer before the recession experienced significantly
      larger increases in depressive symptoms compared with wealthier US workers (beta
      for interaction=-0.054, 95% CI: -0.082 to -0.025), whereas pre-existing wealth
      did not moderate the impact of job loss among European workers. CONCLUSIONS: Job
      loss is associated with increased depressive symptoms in the USA and Europe, but
      effects of job loss due to plant closure are stronger for American workers.
      Wealth mitigates the impact of job loss on depression in the USA more than in
      Europe.

PMID- 24942144
TI  - Animal milk sustains micronutrient nutrition and child anthropometry among
      pastoralists in Samburu, Kenya.
AB  - Milk has been integral to pastoralist nutrition for thousands of years, but as
      communities move toward settled livelihoods, milk consumption is dropping with
      only minimal evidence for the health and nutrition implications. This
      longitudinal study aimed to first test whether increased dependency on
      agriculture reduced household milk production and consumption, and ultimately,
      nutrient adequacy among the Samburu pastoralists. Second, we investigated whether
      household milk availability affected child milk intakes and anthropometry.
      Socioeconomic and dietary intake data were collected from households (n = 200) in
      2000, 2005, and 2010, and anthropometric measures and individual child milk
      intakes in 2012. Nutrient intakes were assessed by the probability of nutrient
      adequacy method, and generalized least-squared regression modeling with mixed
      effects was applied to identify predictors of milk consumption. Milk contributed
      10% of energy intakes, below maize (52%) and sugar (11%), but over one-half of
      critical micronutrients, vitamins A, B12 , and C. Livestock holdings and income
      increased the likelihood of higher milk intakes (overall adj R(2)  = 0.88, P <
      0.001). Undernutrition was widely prevalent among young children: stunting
      (30.6%); underweight (23.9%); and wasting (8.6%). There was evidence for a
      previously described Nilotic body type in the youth, who were taller and thinner
      than the international reference. Milk consumption at the household level was
      positively associated with higher body mass index z scores among youth (P <
      0.001). Programming for livestock development may better ensure micronutrient
      nutrition in Samburu, while deeper investigation into the diet and growth
      patterns of pastoralists could provide insight into leaner and taller
      anthropometrics for other populations globally.

PMID- 24942145
TI  - Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF)
      and possible role of oxidative stress.
AB  - Hormesis, a biphasic dose-response phenomenon, which is characterized by
      stimulation of an end point at a low-dose and inhibition at a high-dose. In the
      present study we used human lungs fibroblast (HELF) cells as a test model to
      evaluate the role of oxidative stress (OS) in hormetic effects of non coplanar
      PCB 101. Results from 3-(4,5-dime-thylthiazol-2-yl)-2,5-diphenyltetrazo-lium
      bromide (MTT) assay indicated that PCB101 at lower concentrations (10(-5) to 10(
      1) MUg mL(-1) ) stimulated HELF cell proliferation and inhibited at high
      concentrations (1, 5, 10, and 20 MUg mL(-1) ) in a dose- and time-dependent
      manner. Reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide
      dismutase (SOD) (except 48 h) showed a significant increase at higher
      concentrations of PCB 101 than those at the lower concentrations with the passage
      of time. Antioxidant enzymes such as glutathione peroxidase (GSH-Px) exhibited
      decreasing trends in dose and time dependent manner. Lipid peroxidation assay
      resulted in a significant increase (P < 0.05) of MDA level in PCB 101-treated
      HELF cells compared with controls, suggesting that OS plays a key role in PCB 101
      induced toxicity. Comet assay indicated a significant increase in genotoxicity at
      higher concentrations of PCB 101 exposure compared to lower concentrations.
      Overall, we found that HELF cell proliferation was higher at low ROS level and
      vice versa, which revealed activation of cell signaling-mediated hormetic
      mechanisms. The results suggested that PCB 101 has hormetic effects to HELF cells
      and these were associated with oxidative stress.

PMID- 24942146
TI  - More than use it or lose it: the number-of-speakers effect on heritage language
      proficiency.
AB  - Acquiring a heritage language (HL), a minority language spoken primarily at home,
      is often a major step toward achieving bilingualism. Two studies examined factors
      that promote HL proficiency. Chinese-English and Spanish-English undergraduates
      and Hebrew-English children named pictures in both their languages, and they or
      their parents completed language history questionnaires. HL picture-naming
      ability correlated positively with the number of different HL speakers
      participants spoke to as children, independently of each language's frequency of
      use, and without negatively affecting English picture-naming ability. HL
      performance increased also when primary caregivers had lower English proficiency,
      with later English age of acquisition, and (in children) with increased age.
      These results suggest a prescription for increasing bilingual proficiency is
      regular interaction with multiple HL speakers. Responsible cognitive mechanisms
      could include greater variety of words used by different speakers,
      representational robustness from exposure to variations in form, or multiple
      retrieval cues, perhaps analogous to contextual diversity effects. 

PMID- 24942147
TI  - Species undersampling in tropical bat surveys: effects on emerging biodiversity
      patterns.
AB  - Undersampling is commonplace in biodiversity surveys of species-rich tropical
      assemblages in which rare taxa abound, with possible repercussions for our
      ability to implement surveys and monitoring programmes in a cost-effective way.
      We investigated the consequences of information loss due to species undersampling
      (missing subsets of species from the full species pool) in tropical bat surveys
      for the emerging patterns of species richness (SR) and compositional variation
      across sites. For 27 bat assemblage data sets from across the tropics, we used
      correlations between original data sets and subsets with different numbers of
      species deleted either at random, or according to their rarity in the assemblage,
      to assess to what extent patterns in SR and composition in data subsets are
      congruent with those in the initial data set. We then examined to what degree
      high sample representativeness (r >= 0.8) was influenced by biogeographic region,
      sampling method, sampling effort or structural assemblage characteristics. For
      SR, correlations between random subsets and original data sets were strong (r >=
      0.8) with moderate (ca. 20%) species loss. Bias associated with information loss
      was greater for species composition; on average ca. 90% of species in random
      subsets had to be retained to adequately capture among-site variation. For
      nonrandom subsets, removing only the rarest species (on average c. 10% of the
      full data set) yielded strong correlations (r > 0.95) for both SR and
      composition. Eliminating greater proportions of rare species resulted in weaker
      correlations and large variation in the magnitude of observed correlations among
      data sets. Species subsets that comprised ca. 85% of the original set can be
      considered reliable surrogates, capable of adequately revealing patterns of SR
      and temporal or spatial turnover in many tropical bat assemblages. Our analyses
      thus demonstrate the potential as well as limitations for reducing survey effort
      and streamlining sampling protocols, and consequently for increasing the cost
      effectiveness in tropical bat surveys or monitoring programmes. The dependence of
      the performance of species subsets on structural assemblage characteristics
      (total assemblage abundance, proportion of rare species), however, underscores
      the importance of adaptive monitoring schemes and of establishing surrogate
      performance on a site by site basis based on pilot surveys. 

PMID- 24942148
TI  - Inhibition of angiogenesis by a synthetic fusion protein VTF derived from
      vasostatin and tumstatin.
AB  - The inhibition of angiogenesis represents a potential strategy for antitumor
      therapy. A novel synthetic fusion protein VTF, composed of bioactive fragments
      from two different angiogenesis inhibitors, vasostatin and tumstatin with a (Gly
      Ser-Gly)2 bridge, was generated using the pET-15b expression vector. The fusion
      protein VTF showed significantly enhanced efficacy in inhibiting human
      endothelial cell proliferation and tube formation and neovascularization on chick
      embryo chorioallantoic membrane. Moreover, VTF suppressed the growth of B16
      melanoma and the formation of tumor blood vessels potently in vivo. These results
      indicated that the fusion protein containing the bioactive fragments of multiple
      angiogenesis inhibitors might be a promising therapeutic agent for tumor
      treatment. 

PMID- 24942149
TI  - Editorial.

PMID- 24942150
TI  - Fourth international consultation on incontinence-research society 2013.

PMID- 24942151
TI  - Guarding the guard cells?

PMID- 24942152
TI  - The danger of mycorrhizal traps?

PMID- 24942153
TI  - Fungal biology: compiling genomes and exploiting them.

PMID- 24942154
TI  - Long-term outcome of delirium during intensive care unit stay in survivors of
      critical illness: a prospective cohort study.
AB  - INTRODUCTION: Delirium is associated with impaired outcome, but it is unclear
      whether this relationship is limited to in-hospital outcomes and whether this
      relationship is independent of the severity of underlying conditions. The aim of
      this study was to investigate the association between delirium in the intensive
      care unit (ICU) and long-term mortality, self-reported health-related quality of
      life (HRQoL), and self-reported problems with cognitive functioning in survivors
      of critical illness, taking severity of illness at baseline and throughout ICU
      stay into account. METHODS: A prospective cohort study was conducted. We included
      patients who survived an ICU stay of at least a day; exclusions were
      neurocritical care patients and patients who sustained deep sedation during the
      entire ICU stay. Delirium was assessed twice daily with the Confusion Assessment
      Method for the ICU (CAM-ICU) and additionally, patients who received haloperidol
      were considered delirious. Twelve months after ICU admission, data on mortality
      were obtained and HRQoL and cognitive functioning were measured with the European
      Quality of Life - Six dimensions self-classifier (EQ-6D). Regression analyses
      were used to assess the associations between delirium and the outcome measures
      adjusted for gender, type of admission, the Acute Physiology And Chronic Health
      Evaluation IV (APACHE IV) score, and the cumulative Sequential Organ Failure
      Assessment (SOFA) score throughout ICU stay. RESULTS: Of 1101 survivors of
      critical illness, 412 persons (37%) had been delirious during ICU stay, and 198
      (18%) died within twelve months. When correcting for confounders, no significant
      association between delirium and long-term mortality was found (hazard ratio:
      1.26; 95% confidence interval (CI) 0.93 to 1.71). In multivariable analysis,
      delirium was not associated with HRQoL either (regression coefficient: -0.04; 95%
      CI -0.10 to 0.01). Yet, delirium remained associated with mild and severe
      problems with cognitive functioning in multivariable analysis (odds ratios: 2.41;
      95% CI 1.57 to 3.69 and 3.10; 95% CI 1.10 to 8.74, respectively). CONCLUSIONS: In
      this group of survivors of critical illness, delirium during ICU stay was not
      associated with long-term mortality or HRQoL after adjusting for confounding,
      including severity of illness throughout ICU stay. In contrast, delirium appears
      to be an independent risk factor for long-term self-reported problems with
      cognitive functioning.

PMID- 24942155
TI  - Phase IV, open-label, randomized study of low-dose recombinant human follicle
      stimulating hormone protocols for ovulation induction.
AB  - BACKGROUND: This Phase IV, open-label, multicentre, randomized study (MEnTOR)
      compared two low-dose recombinant human follicle-stimulating hormone (r-hFSH)
      protocols for ovulation induction. METHODS: This study was conducted in six
      Middle Eastern countries between March 2009 and March 2011. Eligible women (18-37
      years), with World Health Organization Group II anovulatory infertility, were
      randomized to receive r-hFSH (starting daily dose: 75 IU) as a chronic low-dose
      (CLD) (37.5 IU dose increase on Day 14) or low-dose (LD) (37.5 IU dose increase
      on Day 7) protocol if no follicles were >= 10 mm. The maximum r-hFSH daily dose
      permitted was 225 IU/day. The total length of ovarian stimulation could not
      exceed 35 days, unless ultrasound assessment suggested imminent follicular growth
      and maturation. Patients underwent only one treatment cycle. Primary endpoint:
      incidence of mono-follicular development. Secondary endpoints included:
      stimulation duration and rates of bi-follicular development; human chorionic
      gonadotrophin administration rate; clinical pregnancy; and cycle cancellation
      (owing to inadequate response). Adverse events (AEs) were recorded. The primary
      efficacy analysis was performed using data from all patients who received at
      least one dose of correct study medication, had at least one efficacy assessment,
      and no protocol violations at treatment start (CLD group, n=122; LD group,
      n=125). RESULTS: Mono-follicular development rates (primary endpoint) were
      similar in both groups (CLD: 56.6% [69/122] versus LD: 55.2% [69/125], p=0.93;
      primary efficacy analysis population). Similarly, there were no significant
      differences between groups in bi-follicular development, clinical pregnancy or
      cycle cancellation (inadequate response) rates. In patients who received human
      chorionic gonadotrophin injections, the mean duration of stimulation was 13.7
      days in the CLD group and 12.9 days in the LD group. Clinical pregnancy rates for
      those patients who received an hCG injection were similar in both groups (CLD:
      20.2% [19/94] versus LD: 19.8% [18/91], p=0.94; primary efficacy analysis
      population). Most AEs were mild in severity. Only one case of ovarian
      hyperstimulation syndrome was reported (mild; CLD group). CONCLUSIONS: Efficacy
      and safety outcomes were similar for the two protocols.

PMID- 24942157
TI  - Tuning the wettability of mesoporous silica for enhancing the catalysis
      efficiency of aqueous reactions.
AB  - A series of mesoporous silica-based catalysts with finely-tuned surface
      wettability have been synthesized, of which the catalysis efficiency towards
      aqueous hydrogenations is highly dependent on their surface wettability and can
      be five times higher than that of the commercial Pd/C catalyst. 

PMID- 24942156
TI  - Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous,
      including the novel DBA genes TSR2 and RPS28.
AB  - Patients with physical findings suggestive of Treacher Collins syndrome (TCS) or
      mandibulofacial dysostosis (MFD) and macrocytic anemia diagnostic of Diamond
      Blackfan anemia (DBA) have been reported. Disease-causing genes have been
      identified for TCS and other MFDs. Mutations in several ribosomal protein genes
      and the transcription factor GATA1 result in DBA. However, no disease-causing
      mutation had been identified in the reported patients with the combination of
      TCS/MFD and DBA phenotype, and we hypothesized that pathogenic mutations in a
      single gene could be identified using whole exome analysis. We studied probands
      from six unrelated families. Combining exome analysis and Sanger sequencing, we
      identified likely pathogenic mutations in 5/6 families. Two mutations in
      unrelated families were seen in RPS26, the known DBA10 gene. One variant was
      predicted to affect mRNA splicing, and the other to lead to protein truncation.
      In another family a likely pathogenic X-linked mutation affecting a highly
      conserved residue was found in TSR2, which encodes a direct binding partner of
      RPS26. De novo mutations affecting the RPS28 start codon were found in two
      unrelated probands, identifying RPS28 as a novel disease gene. We conclude that
      the phenotype combining features of TCS with DBA is genetically heterogeneous.
      Each of the pathogenic variants identified is predicted to impede ribosome
      biogenesis, which in turn could result in altered cell growth and proliferation,
      causing abnormal embryologic development, defective erythropoiesis and reduced
      growth. The phenotype combining TCS/MFD and DBA is highly variable, overlaps with
      DBA and lies within the phenotypic spectrum of ribosomopathies. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 24942159
TI  - Changing trends in surgical research: an analysis of 30 years of collaborative
      practices.

PMID- 24942158
TI  - No polarization in youth drinking in Stockholm county: response to Hallgren.

PMID- 24942161
TI  - Stalking the mitochondrial ATP synthase: Ina found guilty by association.

PMID- 24942160
TI  - The INA complex facilitates assembly of the peripheral stalk of the mitochondrial
      F1Fo-ATP synthase.
AB  - Mitochondrial F1Fo-ATP synthase generates the bulk of cellular ATP. This
      molecular machine assembles from nuclear- and mitochondria-encoded subunits.
      Whereas chaperones for formation of the matrix-exposed hexameric F1-ATPase core
      domain have been identified, insight into how the nuclear-encoded F1-domain
      assembles with the membrane-embedded Fo-region is lacking. Here we identified the
      INA complex (INAC) in the inner membrane of mitochondria as an assembly factor
      involved in this process. Ina22 and Ina17 are INAC constituents that physically
      associate with the F1-module and peripheral stalk, but not with the assembled
      F1Fo-ATP synthase. Our analyses show that loss of Ina22 and Ina17 specifically
      impairs formation of the peripheral stalk that connects the catalytic F1-module
      to the membrane embedded Fo-domain. We conclude that INAC represents a matrix
      exposed inner membrane protein complex that facilitates peripheral stalk assembly
      and thus promotes a key step in the biogenesis of mitochondrial F1Fo-ATP
      synthase. 

PMID- 24942163
TI  - Regional variation of wall shear stress in ascending thoracic aortic aneurysms.
AB  - The development of an ascending thoracic aortic aneurysm is likely caused by
      excessive hemodynamic loads exerted on the aneurysmal wall. Computational fluid
      dynamic analyses were performed on patient-specific ascending thoracic aortic
      aneurysms obtained from patients with either bicuspid aortic valve or tricuspid
      aortic valve to evaluate hemodynamic and wall shear parameters, imparting
      aneurysm enlargement. Results showed an accelerated flow along the outer aortic
      wall with helical flow in the aneurysm center for bicuspid aortic valve ascending
      thoracic aortic aneurysms. In a different way, tricuspid aortic valve ascending
      thoracic aortic aneurysms exhibited normal systolic flow without substantial
      secondary pattern. Analysis of wall shear parameters evinced a high and locally
      varying wall shear stress on the outer aortic wall and high temporal oscillations
      in wall shear stress (oscillatory shear index) on either left or right side of
      aneurysmal aorta. These findings may explain the asymmetric dilatation typically
      observed in ascending thoracic aortic aneurysms. Simulations of a hypertensive
      scenario revealed an increase in wall shear stress upon 44% compared to normal
      systemic pressure models. Computational fluid-dynamics-based analysis may allow
      identification of wall shear parameters portending aneurysm dilatation and hence
      guide preventative intervention.

PMID- 24942162
TI  - Pink1, the first ubiquitin kinase.

PMID- 24942164
TI  - Training load quantification in elite swimmers using a modified version of the
      training impulse method.
AB  - Prior reports have described the limitations of quantifying internal training
      loads using hear rate (HR)-based objective methods such as the training impulse
      (TRIMP) method, especially when high-intensity interval exercises are performed.
      A weakness of the TRIMP method is that it does not discriminate between exercise
      and rest periods, expressing both states into a single mean intensity value that
      could lead to an underestimate of training loads. This study was designed to
      compare Banister's original TRIMP method (1991) and a modified calculation
      procedure (TRIMPc) based on the cumulative sum of partial TRIMP, and to determine
      how each model relates to the session rating of perceived exertion (s-RPE), a HR
      independent training load indicator. Over four weeks, 17 elite swimmers completed
      328 pool training sessions. Mean HR for the full duration of a session and
      partial values for each 50 m of swimming distance and rest period were recorded
      to calculate the classic TRIMP and the proposed variant (TRIMPc). The s-RPE
      questionnaire was self-administered 30 minutes after each training session. Both
      TRIMPc and TRIMP measures strongly correlated with s-RPE scores (r = 0.724 and
      0.702, respectively; P < 0.001). However, TRIMPc was ~ 9% higher on average than
      TRIMP (117 +/- 53 vs. 107 +/- 47; P < 0.001), with proportionally greater inter
      method difference with increasing workload intensity. Therefore, TRIMPc appears
      to be a more accurate and appropriate procedure for quantifying training load,
      particularly when monitoring interval training sessions, since it allows
      weighting both exercise and recovery intervals separately for the corresponding
      HR-derived intensity.

PMID- 24942166
TI  - Relationship between unilateral jumping ability and asymmetry on multidirectional
      speed in team-sport athletes.
AB  - Relationship between unilateral jumping ability and asymmetry on multidirectional
      speed in team-sport athletes. J Strength Cond Res 28(12): 3557-3566, 2014-The
      influence of unilateral jump performance, and between-leg asymmetries, on
      multidirectional speed has not been widely researched. This study analyzed how
      speed was related to unilateral jumping. Multidirectional speed was measured by
      20-m sprint (0-5, 0-10, 0-20-m intervals), left- and right-leg turn 505, and
      modified T-test performance. Unilateral jump performance, and between-leg
      asymmetries, was measured by vertical (VJ), standing broad (SBJ), and lateral
      (LJ) jumping. Thirty male team-sport athletes (age = 22.60 +/- 3.86 years; height
      = 1.80 +/- 0.07 m; mass = 79.03 +/- 12.26 kilograms) were recruited. Pearson's
      correlations (r) determined speed and jump performance relationships; stepwise
      regression ascertained jump predictors of speed (p <= 0.05). Subjects were
      divided into lesser and greater asymmetry groups from each jump condition. A 1
      way analysis of variance found between-group differences (p <= 0.05). Left-leg VJ
      correlated with the 0-10 and 0-20-m intervals (r = -0.437 to -0.486). Right-leg
      VJ correlated with all sprint intervals and the T-test (r = -0.380 to -0.512).
      Left-leg SBJ and LJ correlated with all tests (r = -0.370 to -0.729). Right-leg
      SBJ and LJ related to all except the left-leg turn 505 (r = -0.415 to -0.650).
      Left-leg SBJ predicted the 20-m sprint. Left-leg LJ predicted the 505 and T-test.
      Regardless of the asymmetry used to form groups, no differences in speed were
      established. Horizontal and LJ performance related to multidirectional speed.
      Athletes with asymmetries similar to this study (VJ = ~10%; SBJ = ~3%; LJ = ~5%)
      should not experience speed detriments.

PMID- 24942167
TI  - Detecting deficits in change of direction performance using the preplanned
      multidirectional Australian football league agility test.
AB  - The Australian Football League (AFL) agility test is a preplanned
      multidirectional circuit involving 5 directional changes of various magnitudes
      that might differently assess athletes of particular leg dominance. This study
      served to establish whether the AFL agility test appropriately examines athletes
      of differing limb dominance, while also quantifying performance deficits
      prevalent between limbs of Australian Footballers. Fifty-eight Australian
      Footballers were recruited from the Western Australian Football League (age =
      21.9 +/- 2.8 years; height = 183.7 +/- 5.9 cm; weight = 86.4 +/- 4.7 kg). Two
      circuits of the AFL agility test were set up in accordance with official
      specifications. The finish line of the second circuit was relocated to the
      opposite side to modify the starting direction. Footballers were randomized and
      counterbalanced between versions, performing 3 trials in each direction. Paired t
      tests (p <= 0.05) were used to examine differences between dominant and
      nondominant trials. Independent t-tests (p <= 0.05) were used to identify
      differences between left and right leg dominant groups. The current version of
      the AFL agility test appropriately examined ~61% of footballers in this cohort.
      The remaining ~39% produced significantly faster times during the alternate
      version (0.63-0.82 seconds; p <= 0.001). All footballers demonstrated a
      performance deficit of 5-10% between limbs (~0.72 seconds; p <= 0.001). Limb
      dominance (directional preference) was evident for all footballers. Change of
      direction capabilities should therefore be examined bilaterally to eliminate bias
      toward athletes with particular leg dominance profiles and to provide a limb
      deficit measure for enhanced athletic profiling outcomes.

PMID- 24942165
TI  - Next-generation sequencing of small RNAs from inner ear sensory epithelium
      identifies microRNAs and defines regulatory pathways.
AB  - BACKGROUND: The mammalian inner ear contains sensory organs, the organ of Corti
      in the cochlea and cristae and maculae in the vestibule, with each comprised of
      patterned sensory epithelia that are responsible for hearing and balance. The
      development, cell fate, patterning, and innervation of both the sensory and
      nonsensory regions of the inner ear are governed by tight regulation involving,
      among others, transcription factors and microRNAs (miRNAs). In humans, mutations
      in specific miRNA genes are associated with hearing loss. In mice, experimental
      reduction or mutations of miRNAs in the inner ear leads to severe developmental
      and structural abnormalities. A comprehensive identification of miRNAs in the
      sensory epithelia and their gene targets will enable pathways of auditory and
      vestibular function to be defined. RESULTS: In this study, we used Next
      Generation Sequencing (NGS) to identify the most prominent miRNAs in the inner
      ear and to define miRNA-target pairs that form pathways crucial for the function
      of the sensory epithelial cells. NGS of RNA from inner ear sensory epithelial
      cells led to the identification of 455 miRNAs in both cochlear and vestibular
      sensory epithelium, with 30 and 44 miRNAs found in only cochlea or vestibule,
      respectively. miR-6715-3p and miR-6715-5p were defined for the first time in the
      inner ear. Gene targets were identified for each of these miRNAs, including
      Arhgap12, a GTPase activating protein, for miR-6715-3p, implicating this miRNA in
      sensory hair cell bundle development, actin reorganization, cell adhesion and
      inner ear morphogenesis. CONCLUSIONS: This study provides a comprehensive atlas
      of miRNAs in the inner ear sensory epithelia. The results provide further support
      of the essential regulatory role of miRNAs in inner ear sensory epithelia and in
      regulating pathways that define development and growth of these cells.

PMID- 24942169
TI  - Testing Game-Based Performance in Team-Handball.
AB  - Wagner, H, Orwat, M, Hinz, M, Pfusterschmied, J, Bacharach, DW, von Duvillard,
      SP, and Muller, E. Testing game-based performance in team-handball. J Strength
      Cond Res 30(10): 2794-2801, 2016-Team-handball is a fast paced game of defensive
      and offensive action that includes specific movements of jumping, passing,
      throwing, checking, and screening. To date and to the best of our knowledge, a
      game-based performance test (GBPT) for team-handball does not exist. Therefore,
      the aim of this study was to develop and validate such a test. Seventeen
      experienced team-handball players performed 2 GBPTs separated by 7 days between
      each test, an incremental treadmill running test, and a team-handball test game
      (TG) (2 * 20 minutes). Peak oxygen uptake (V[Combining Dot Above]O2peak), blood
      lactate concentration (BLC), heart rate (HR), sprinting time, time of offensive
      and defensive actions as well as running intensities, ball velocity, and jump
      height were measured in the game-based test. Reliability of the tests was
      calculated using an intraclass correlation coefficient (ICC). Additionally, we
      measured V[Combining Dot Above]O2peak in the incremental treadmill running test
      and BLC, HR, and running intensities in the team-handball TG to determine the
      validity of the GBPT. For the test-retest reliability, we found an ICC >0.70 for
      the peak BLC and HR, mean offense and defense time, as well as ball velocity that
      yielded an ICC >0.90 for the V[Combining Dot Above]O2peak in the GBPT. Percent
      walking and standing constituted 73% of total time. Moderate (18%) and high (9%)
      intensity running in the GBPT was similar to the team-handball TG. Our results
      indicated that the GBPT is a valid and reliable test to analyze team-handball
      performance (physiological and biomechanical variables) under conditions similar
      to competition. 

PMID- 24942170
TI  - Effects of a 12-week strength training program on experimented fencers' movement
      time.
AB  - The purpose of this study was to determine the effects of a 12-week strength
      training program on movement time (MT) on fencers of national level. Twelve male
      fencers were randomly divided into 2 groups: the control group (CG: N = 6; age,
      22.3 +/- 8.1 years) and the treatment group (TG: N = 6; age, 24.8 +/- 7.2 years).
      The CG fencers followed the standard physical conditioning program, which was
      partially modified for the TG. The TG participated in a 12-week strength training
      program divided into 2 parts: maximal strength training, including weightlifting
      exercises (2 days a week for 6 weeks) and explosive strength training, with
      combined weights and plyometric exercises (2 days a week for 6 weeks). Body mass,
      body fat, muscle mass, jumping ability, maximal strength, reaction time, and MT
      were measured on 4 separate occasions. The TG demonstrated significant increases
      (p <= 0.05) in maximal strength and jumping ability after 6 weeks of training and
      in MT after 12 weeks. These improvements remained unaltered during the 4-week
      detraining period. It may be concluded that a 12-week strength training program
      can improve maximal and explosive strength, and these increases can be
      transferred to MT performance. However, fencers need time to transfer the gains.

PMID- 24942171
TI  - The Acute Effects of Static Stretching on Speed and Agility Performance Depend on
      Stretch Duration and Conditioning Level.
AB  - Avloniti, A, Chatzinikolaou, A, Fatouros, IG, Avloniti, C, Protopapa, M,
      Draganidis, D, Stampoulis, T, Leontsini, D, Mavropalias, G, Gounelas, G, and
      Kambas, A. The acute effects of static stretching on speed and agility
      performance depend on stretch duration and conditioning level. J Strength Cond
      Res 30(10): 2767-2773, 2016-Although static stretching (SS) is an integral part
      of physical preparation before training and competition, its usefulness in
      regards to power performance improvement has been questioned. The aim of this
      study was to investigate the effect of 6 SS durations on speed and agility
      performance. According to a cross-over design, 34 trained men (age, 20.5 +/- 1.4
      years; height, 1.81 +/- 0.2 m; weight, 77.2 +/- 2.6 kg; body fat, 8.2 +/- 2.6%)
      participated in a control session (no stretch) and 6 experimental conditions (10,
      15, 20, 30, 40, and 60 seconds) performed in a randomized order. Performance in
      speed (10 and 20 m) and agility (T-test) was measured after the control and
      experimental conditions. Static stretching, consisting of stretches for hip
      extensors, hip adductors, knee extensors, knee flexors, and ankle sole flexors,
      was performed after light cardiovascular exercise (8 minutes). A 1-way repeated
      measures analysis of variance showed that speed was improved only by SS of short
      duration (15/20 seconds), whereas agility remained unaffected by all SS trials.
      When participants' speed and agility level was taken into account, it was
      revealed that only those of moderate performance demonstrated an improved speed
      (in 15- and 20-second trials) and agility (in 10- and 15-second trials)
      performance. These results suggest that short-duration SS protocols induce an
      acute improvement of speed and agility performance, whereas longer-duration SS
      protocols have neither positive nor negative effect. Furthermore, it seems that
      individuals of lower speed and agility performance level are more likely to
      benefit by a short-duration SS protocol. 

PMID- 24942172
TI  - Relationship between selected measures of strength and hip and knee excursion
      during unilateral and bilateral landings in women.
AB  - The purpose of this study was to compare the relationship between several
      measures of single-joint, isometric, eccentric, and squat strength and unilateral
      and bilateral landing mechanics at the hip and knee in women. Twenty six healthy
      female subjects with previous athletic experience (height, 165.1 +/- 7.01 cm;
      mass, 60.91 +/- 7.14 kg; age, 20.9 +/- 1.62 years) participated in this study.
      Hip and knee mechanics were measured using the MotionMonitor capture system
      (Innovative Sports Training, Inc.) with 3-dimensional electromagnetic sensors
      during bilateral (60 cm) and unilateral drop jumps (30 cm). On a separate day,
      isometric hip extension, external rotation, and abduction strength (lbs) were
      measured using a handheld dynamometer (Hoggan Health Industries, Inc.). Eccentric
      and isometric knee strength were measured on the Biodex IV Isokinetic Dynamometer
      (Biodex Medical Systems, Inc.). Free weight was used to measure the bilateral
      squat and a modified single-leg squat. The strongest correlations were found
      between squat strength and knee valgus (-0.77 <= r <= -0.83) and hip adduction (
      0.5 <= r <= -0.65). After controlling for squat strength, hip external rotation
      strength and unilateral knee valgus (-0.41), hip abduction strength and bilateral
      knee valgus (-0.43), and knee flexion strength and bilateral hip adduction (
      0.57) remained significant. Eccentric knee flexion strength and unilateral knee
      internal rotation was the only significant correlation for eccentric strength (
      0.40). Squat strength seems to be the best predictor of knee valgus and was
      consistently related to hip adduction. Isometric and eccentric measures
      demonstrated few significant correlations with hip and knee excursion while
      demonstrating a low-to-moderate relationship. Hip and knee flexion and rotation
      do not seem to be related to strength. Squat strength should receive
      consideration during risk assessment for noncontact knee injury.

PMID- 24942173
TI  - Effects of acute dehydration on neuromuscular responses of exercised and
      nonexercised muscles after exercise in the heat.
AB  - Dehydration can impair aerobic performance, but its effects on muscular strength
      are still unclear. This study evaluated the effect of dehydration induced by
      cycling in the heat on exercised (knee extensors) and nonexercised (elbow
      flexors) muscles' strength and activation. Ten healthy recreationally active and
      nonacclimatized men (age, 22.71 +/- 2.21 years old; body mass (BM), 77.94 +/-
      7.35 kg; height, 1.76 +/- 6.46 m; body fat, 18.93 +/- 3.01%) cycled in the heat
      in 2 separate sessions: dehydrated (DHY) and euhydrated (EUH). Dehydrated session
      led to a 2% BM loss, and water ingestion prevented the water loss in the
      euhydrated session. Knee extensor and elbow flexor maximal isometric torques and
      muscle activation were assessed before and after exercising in both sessions.
      Knee extensor torque decreased 15.8% (p < 0.001; 294.27 +/- 44.82-247.16 +/-
      40.54) in dehydrated session, whereas no significant reduction (2.98%; p = 0.348;
      291.99 +/- 48.37-281.74 +/- 38.65) was observed in the euhydrated session. No
      significant session-time interaction (p = 0.098) was observed for elbow flexor
      responses (DHY, 67.51 +/- 14.53-62.95 +/- 13.60; EUH, 68.26 +/- 13.06-67.87 +/-
      13.89). Muscle activation capacity was unaffected by the hydration status.
      Maintenance of euhydration state during cycling in the heat may attenuate
      strength impairments caused by water loss in exercised muscle groups.

PMID- 24942174
TI  - Comparison of the acute metabolic responses to traditional resistance, body
      weight, and battling rope exercises.
AB  - The purpose of this study was to quantify and compare the acute metabolic
      responses to resistance exercise protocols comprising free-weight, body-weight,
      and battling rope (BR) exercises. Ten resistance-trained men (age = 20.6 +/- 1.3
      years) performed 13 resistance exercise protocols on separate days in random
      order consisting of only one exercise per session. For free-weight exercise
      protocols, subjects performed 3 sets of up to 10 repetitions with 75% of their 1
      repetition maximum. For the push-up (PU) and push-up on a BOSU ball protocols,
      subjects performed 3 sets of 20 repetitions. For the burpee and PU with lateral
      crawl protocols, subjects performed 3 sets of 10 repetitions. For the plank and
      BR circuit protocols, subjects performed 3 sets of 30-second bouts. A standard 2
      minute rest interval (RI) was used in between all sets for each exercise. Data
      were averaged for the entire protocol including work and RIs. Mean oxygen
      consumption was significantly greatest during the BR (24.6 +/- 2.6 ml.kg.min) and
      burpee (22.9 +/- 2.1 ml.kg.min) protocols. For the free-weight exercises, highest
      mean values were seen in the squat (19.6 +/- 1.8 ml.kg.min), deadlift (18.9 +/-
      3.0 ml.kg.min), and lunge (17.3 +/- 2.6 ml.kg.min). No differences were observed
      between PUs performed on the floor vs. on a BOSU ball. However, adding a lateral
      crawl to the PU significantly increased mean oxygen consumption (19.5 +/- 2.9
      ml.kg.min). The lowest mean value was seen during the plank exercise (7.9 +/- 0.7
      ml.kg.min). These data indicate performance of exercises with BRs and a body
      weight burpee exercise elicit relatively higher acute metabolic demands than
      traditional resistance exercises performed with moderately heavy loading.

PMID- 24942175
TI  - Effects of traditional vs. alternating whole-body strength training on squat
      performance.
AB  - Traditional strength training with 80% of 1 repetition maximum (1RM) uses 2- to 5
      minute rest periods between sets. These long rest periods minimize decreases in
      volume and intensity but result in long workouts. Performing upper-body exercises
      during lower-body rest intervals may decrease workout duration but may affect
      workout performance. Therefore, the purpose of this study was to compare the
      effects of traditional vs. alternating whole-body strength training on squat
      performance. Twenty male (24 +/- 2 years) volunteers performed 2 workouts. The
      traditional set (TS) workout consisted of 4 sets of squats (SQ) at 80% of 1RM on
      a force plate with 3-minute rest between sets. The alternating set (AS) workout
      also consisted of 4 sets of SQ at 80% of 1RM but with bench press, and bench pull
      exercises performed between squat sets 1, 2 and 3 with between-exercise rest of
      50 seconds, resulting in approximately 3-minute rest between squat sets. Sets 1-3
      were performed for 4 repetitions, whereas set 4 was performed to concentric
      failure. Total number of completed repetitions of the fourth squat set to failure
      was recorded. Peak ground reaction force (GRF), peak power (PP), and average
      power (AP) of every squat repetition were recorded and averaged for each set.
      There was no significant interaction for GRF, PP, or AP. However, volume-equated
      AP was greater during the TS condition (989 +/- 183) than the AS condition (937
      +/- 176). During the fourth squat set, the TS condition resulted in more
      repetitions to failure (7.5 +/- 2.2) than the AS condition (6.5 +/- 2.2).
      Therefore, individuals who aim to optimize squat AP should refrain from
      performing more than 3 ASs per exercise. Likewise, those who aim to maximize
      squat repetitions to failure should refrain from performing upper-body multijoint
      exercises during squat rest intervals.

PMID- 24942176
TI  - Effect of cluster sets on plyometric jump power.
AB  - Cluster sets may lead to enhanced power (PW) production by allowing for partial
      recovery. The purpose of this study was to determine the effects of cluster sets
      vs. traditional sets on plyometric jump PW, ground reaction force, take-off
      velocity (TOV), and jump height (JH). Twenty-six recreationally trained college
      men completed 3 testing sessions, which involved performing repeated body-weight
      (BW) plyometric squat jumps across 3 different set configurations: traditional (2
      sets of 10 with 90-second rest between sets), cluster 1 (4 sets of 5 with 30
      second rest between sets), and cluster 2 (10 sets of 2 with 10-second rest
      between sets). Ground reaction force results demonstrated no interaction or main
      effect for condition, but there was a significant (p <= 0.05) main effect for
      repetition, where repetition 1 was significantly less than repetitions 3-5, 7-10,
      12-15, and 17-20. For TOV, PW, and JH, there were significant interactions. Take
      off velocity resulted in the following: Traditional, repetition 1 was
      significantly greater than repetitions 7-10 and 17-20, but was significantly less
      than repetition 13; cluster 1, repetition 1 was significantly less than
      repetitions 2-5; and cluster 2, there were no significant differences. Power
      resulted in the following: Traditional, repetition 1 was significantly greater
      than repetitions 4-10 and 14-20; cluster 1, repetition 1 was significantly
      greater than repetitions 7-10 and 12-20; and cluster 2, repetition 1 was
      significantly greater than repetitions 3, 6-18, and 20. Jump height resulted in
      the following: Traditional, repetition 1 was significantly greater than
      repetitions 18-20, but was significantly less than repetitions 3 and 13. For
      cluster 1 and cluster 2, there were no significant differences. These results
      demonstrate that cluster sets, specifically 10 sets of 2, allow for a greater
      maintenance of PW, TOV, and JH compared with a traditional 2 sets of 10 when
      performing repeated BW plyometric squat jumps. A lack of training data precludes
      definitive recommendations; however, based on these data, coaches should have
      their athletes perform 2-5 jumps with 27-45 seconds of rest, respectively.

PMID- 24942177
TI  - Rapid detection of enterobacteriaceae producing extended spectrum beta-lactamases
      directly from positive blood cultures by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry.
AB  - Bacteria that produce extended-spectrum beta-lactamases (ESBLs) are an increasing
      healthcare problem and their rapid detection is a challenge that must be overcome
      in order to optimize antimicrobial treatment and patient care. Matrix-assisted
      laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has
      been used to determine resistance to beta-lactams, including carbapenems in
      Enterobacteriaceae, but the methodology has not been fully validated as it
      remains time-consuming. We aimed to assess whether MALDI-TOF can be used to
      detect ESBL-producing Enterobacteriaceae from positive blood culture bottles in
      clinical practice. In the assay, 141 blood cultures were tested, 13 of them were
      real bacteraemias and 128 corresponded to blood culture bottles seeded with
      bacterial clinical isolates. Bacteraemias were analysed by MALDI-TOF after a
      positive growth result and the 128 remaining blood cultures 24 h after the
      bacterial seeding. beta-lactamase activity was determined through the profile of
      peaks associated with the antibiotics cefotaxime and ceftazidime and its
      hydrolyzed forms. Clavulanic acid was added to rule out the presence of non-ESBL
      mechanisms. Overall data show a 99% (103 out of 104) sensitivity in detecting
      ESBL in positive blood cultures. Data were obtained in 90 min (maximum 150 min).
      The proposed methodology has a great impact on the early detection of ESBL
      producing Enterobacteriaceae from positive blood cultures, being a rapid and
      efficient method and allowing early administration of an appropriate antibiotic
      therapy. 

PMID- 24942178
TI  - A comparison of off-pump and on-pump coronary bypass surgery in patients with low
      EuroSCORE.
AB  - BACKGROUND: The aim of the present study was to evaluate and compare
      postoperative short-term, mid-term and long-term outcomes of coronary artery
      bypass surgery performed with or without cardiopulmonary bypass in patients with
      a low European System for Cardiac Operative Risk Evaluation score. METHODS: A
      retrospective analysis of 478 consecutive low risk patients undergoing coronary
      bypass surgery between January 2002 and December 2007 was performed. Of these
      patients, 83 cases had undergone on-pump and 395 cases had undergone off-pump
      coronary bypass surgery. The patients were assessed in terms peri-operative
      complications, survival, mortality due to cardiac events, need for
      rehospitalization and repeated coronary revascularization. RESULTS: There was no
      significant difference between the two groups in terms of preoperative
      characteristics, except for chronic obstructive pulmonary disease. The number of
      distal anastomosis per patient was significantly lower in the off-pump group than
      in the on-pump group (2.66 +/- 0.74 vs. 3.21 +/- 0.85, p < 0.001). Early
      mortality rates were similar in both groups (1.01% for the off-pump group and
      1.2% for the on-pump group, p = 0.687). Neurological complications were
      significantly lower in the off-pump group than in the on-pump group (1.1% vs. 6%,
      p = 0.01). The mean follow-up period was 80 +/- 19.1 months (range, 3-112
      months). The need for revascularization during long-term follow-up was 10.1% in
      the off-pump group and 7.2% in the on-pump group (p = 0.416). The 5-year survival
      was 95.2 +/- 1.1% and 95.5 +/- 2.7% in the off-pump and on-pump groups,
      respectively (p = 0.8), whereas the 7-year survival was 91.9 +/- 1.6% and 84.7 +/
      6.8% in the off-pump and on-pump groups, respectively (p = 0.274). The 5-year
      revascularization-free period was 89.5 +/- 1.6% and 89.7 +/- 3.5% in the off-pump
      and on-pump groups, respectively (p = 0.785). The 7-year revascularization-free
      period was 71.1 +/- 3.1% and 73.5 +/- 7.3% in the off-pump and on-pump groups,
      respectively (p = 0.075). The 7-year event-free survival was 80.1 +/- 2.2% and
      73.4 +/- 7.3% in the off-pump and on-pump groups, respectively (p = 0.377).
      CONCLUSIONS: The present study demonstrated that off-pump cardiac surgery had
      advantages over on-pump cardiac surgery in the short term; however, both
      interventions had similar mid-term and long-term outcomes, when performed in low
      risk patient.

PMID- 24942179
TI  - Proteinuria and hematuria are associated with acute kidney injury and mortality
      in critically ill patients: a retrospective observational study.
AB  - BACKGROUND: Proteinuria and hematuria are both important health issues; however,
      the nature of the association between these findings and acute kidney injury
      (AKI) or mortality remains unresolved in critically ill patients. METHODS:
      Proteinuria and hematuria were measured by a dipstick test and scored using a
      scale ranging from a negative result to 3+ in 1883 patients admitted to the
      intensive care unit. AKI was defined according to the Kidney Disease: Improving
      Global Outcomes (KDIGO) guidelines. The odds ratios (ORs) for AKI and 3-year
      mortality were calculated after adjustment for multiple covariates according to
      the degree of proteinuria or hematuria. For evaluating the synergistic effect on
      mortality among proteinuria, hematuria, and AKI, the relative excess risk due to
      interaction (RERI) was used. RESULTS: Proteinuria and hematuria increased the ORs
      for AKI: the ORs of proteinuria were 1.66 (+/-), 1.86 (1+), 2.18 (2+), and 4.74
      (3+) compared with non-proteinuria; the ORs of hematuria were 1.31 (+/-), 1.58
      (1+), 2.63 (2+), and 2.52 (3+) compared with non-hematuria. The correlations
      between the mortality risk and proteinuria or hematuria were all significant and
      graded (Ptrend<0.001). There was a relative excess risk of mortality when both
      AKI and proteinuria or hematuria were considered together: the synergy indexes
      were 1.30 and 1.23 for proteinuria and hematuria, respectively. CONCLUSIONS:
      Proteinuria and hematuria are associated with the risks of AKI and mortality in
      critically ill patients. Additionally, these findings had a synergistic effect
      with AKI on mortality.

PMID- 24942181
TI  - The reinvestigation of the kinetics of the metathesis reactions t-C4H9* + HBr
      (HI) -> i-C4H10 + Br* (I*) and of the t-C4H9* free radical thermochemistry.
AB  - A reinvestigation of the absolute rate constant of the metathesis reactions t
      C4H9* + HBr -> i-C4H10 + Br* (1) and t-C4H9* + HI -> i-C4H10 + I* (2) was
      performed thanks to a recently developed apparatus consisting of a Knudsen
      reactor coupled to detection based on single-photon (VUV) photoionization mass
      spectrometry (SPIMS). It enables the generation of thermalized hydrocarbon free
      radicals owing to a source upstream of and external to the Knudsen reactor. The
      following Arrhenius expressions were obtained: k1 = 5.6(+/-1.4) * 10(-12) exp(
      6.76(+/-0.94)/(RT)) and k2 = 2.0(+/-0.6) * 10(-11) exp(-8.48(+/-0.94)/(RT)) with
      R = 8.314 J mol(-1) K(-1) over the range 293 to 623 K. The mass balance of the
      reaction system based on closed shell product detection (CSPD) was checked in
      order to ensure the accuracy of the used reaction mechanism and as an independent
      check of k1 and k2. The wall-loss rate constants of the t-butyl free radical,
      kw(C4H9), were measured and found to be low compared with the corresponding
      escape rate constant, ke(C4H9), for effusion of t-C4H9* out of the Knudsen
      reactor. On the basis of the present results, the free radical standard heat of
      formation DeltafH298 degrees (t-C4H9*) = 44.3 +/- 1.7 kJ mol(-1) was obtained
      when combined with the kinetics of the inverse halogenation reaction taken from
      the literature and using S298 degrees (t-C4H9*) = 322.2 J K(-1) mol(-1) following
      a "Third Law" evaluation method. The standard enthalpy for t-butyl free radical
      is consistent for both the bromination and iodination reactions within the stated
      uncertainties.

PMID- 24942180
TI  - Intentions to donate to a biobank in a national sample of African Americans.
AB  - BACKGROUND/AIMS: Despite the investments being made to develop biobanks, African
      Americans are under-represented in genomic studies. We identified factors having
      significant independent associations with intentions to donate personal health
      information and blood and/or tissue samples to a biobank in a national random
      sample of African Americans (n = 1,033). METHODS: We conducted a national survey
      from October 2010 through February 2011. RESULTS: Twenty-three percent of
      respondents reported that it was not at all likely that they would donate to a
      biobank, 18% reported it was a little likely, 36% reported it was somewhat
      likely, and 23% reported it was very likely. Respondents who were likely to
      donate to a biobank had greater positive expectations about participating in
      cancer genetics research and reported more participation facilitators relative to
      barriers. Respondents who were distrustful of researchers had a significantly
      lower likelihood of being willing to donate to a biobank compared to those who
      were less distrustful. CONCLUSIONS: African Americans have diverse attitudes
      about participating in genetics research, and many are likely to donate to a
      biobank based on expectations of positive outcomes. It may be important to
      address attitudes about genetics research as part of recruitment to enhance the
      quality of informed consent for participation in biobanks among African
      Americans.

PMID- 24942182
TI  - Cluster analysis reveals a binary effect of storage on boar sperm motility
      function.
AB  - Storage of liquid-preserved boar spermatozoa is associated with a loss of
      fertilising ability of the preserved spermatozoa, which standard semen parameters
      barely reflect. Monitoring responses to molecular effectors of sperm function
      (e.g. bicarbonate) has proven to be a more sensitive approach to investigating
      storage effects. Bicarbonate not only initiates capacitation in spermatozoa, but
      also induces motility activation. This occurs at ejaculation, but also happens
      throughout passage through the oviduct. In the present study we tested whether
      the specific response of boar sperm subpopulations to bicarbonate, as assessed by
      motility activation, is altered with the duration of storage in vitro. Three
      ejaculates from each of seven boars were diluted in Beltsville thawing solution
      and stored at 17 degrees C. Only minor changes in the parameters of diluted semen
      were revealed over a period of 72h storage. For assessment of bicarbonate
      responses, subsamples of diluted spermatozoa were centrifuged through a
      discontinuous Percoll gradient after 12, 24 and 72h storage. Subsequently,
      spermatozoa were incubated in two Ca2+-free variants of Tyrode's medium either
      without (TyrControl) or with (TyrBic) 15mM bicarbonate, and computer-aided sperm
      analysis motility measurements were made. Cluster analysis of imaging data from
      motile spermatozoa revealed the presence of five major sperm subpopulations with
      distinct motility characteristics, differing between TyrBic and TyrControl at any
      given time (P<0.001). Although there was an increasing loss of motility function
      in both media, bicarbonate induced an increase in a 'fast linear' cohort of
      spermatozoa in TyrBic regardless of storage (66.4% at 12h and 63.9% at 72h).
      These results imply a binary pattern in response of sperm motility function
      descriptors to storage: although the quantitative descriptor (percentage of
      motile spermatozoa) declines in washed semen samples, the qualitative descriptor
      (percentage of spermatozoa stimulated into fast linear motion by bicarbonate) is
      sustained independent of the duration of storage. 

PMID- 24942183
TI  - Identification of bovine embryos cultured in groups by attachment of barcodes to
      the zona pellucida.
AB  - The low number of oocytes collected from unstimulated donors by ovum pick-up
      means that embryos produced from each individual female have to be cultured
      individually or in very small groups. However, it has been demonstrated that
      single-embryo culture is less efficient than embryo culture in groups. To
      overcome this limitation, we developed a direct embryo-tagging system, which
      allows the collective culture of embryos from different origins whilst preserving
      their pedigree. Presumptive bovine zygotes were tagged with eight wheat-germ
      agglutinin biofunctionalised polysilicon barcodes attached to the outer surface
      of the zona pellucida (ZP). Four different barcodes were used to encode groups of
      20-25 embryos, which were then cultured in the same drop. Cleavage, Day-7 and Day
      8 blastocysts and barcode retention rates were assessed. In addition, Day-7
      blastocysts were vitrified and warmed. Barcode attachment to the ZP of bovine
      embryos affected neither in vitro embryo development nor post-warming survival of
      the tagged embryos. All the embryos maintained barcodes attached until Day 8 of
      culture (3.63+/-0.37 barcodes per embryo) and could be identified. In conclusion,
      identification of embryos by barcodes attached to the ZP is feasible and will
      allow the culture of embryos from different donors in the same drop. 

PMID- 24942184
TI  - Precise spatio-temporal modulation of ACC synthase by MPK6 cascade mediates the
      response of rose flowers to rehydration.
AB  - Drought is a major abiotic stress that affects the development and growth of most
      plants, and limits crop yield worldwide. Although the response of plants to
      drought has been well documented, much less is known about how plants respond to
      the water recovery process, namely rehydration. Here, we describe the spatio
      temporal response of plant reproductive organs to rehydration using rose flowers
      as an experimental system. We found that rehydration triggered rapid and
      transient ethylene production in the gynoecia. This ethylene burst serves as a
      signal to ensure water recovery in flowers, and promotes flower opening by
      influencing the expression of a set of rehydration-responsive genes. An in-gel
      kinase assay suggested that the rehydration-induced ethylene burst resulted from
      transient accumulation of RhACS1/2 proteins in gynoecia. Meanwhile, RhMPK6, a
      rose homolog of Arabidopsis thaliana MPK6, is rapidly activated by rehydration
      within 0.5 h. Furthermore, RhMPK6 was able to phosphorylate RhACS1 but not RhACS2
      in vitro. Application of the kinase inhibitor K252a suppressed RhACS1
      accumulation and rehydration-induced ethylene production in gynoecia, and the
      protein phosphatase inhibitor okadaic acid had the opposite effect, confirming
      that accumulation of RhACS1 was phosphorylation-dependent. Finally, silencing of
      RhMPK6 significantly reduced ethylene production in gynoecia when flowers were
      subjected to rehydration. Taken together, our results suggest that temporal- and
      spatial-specific activation of an RhMPK6-RhACS1 cascade is responsible for
      rehydration-induced ethylene production in gynoecia, and that the resulting
      ethylene-mediated signaling pathway is a key factor in flower rehydration. 

PMID- 24942185
TI  - Astragalus membranaceus up-regulate Cosmc expression and reverse IgA dys
      glycosylation in IgA nephropathy.
AB  - BACKGROUND: Decreased Core I beta3-Gal-T-specific molecular chaperone (Cosmc)
      expression induced IgA1 aberrant glycosylation is the main characteristic of IgA
      nephropathy (IgAN). This study tried to elucidate the effect of Astragalus
      membranaceus on Cosmc expression and IgA O-glycosylation of peripheral B
      lymphocytes in IgAN patients. METHODS: Peripheral B lymphocytes of 21 IgAN
      patients and 10 normal controls were isolated and cultured with or without
      lipopolysaccharide (LPS) and Astragalus membranaceus injection (AMI). Cosmc mRNA
      and protein expression levels were measured by real-time RT-PCR and Western blot.
      IgA1 and glycosylation level were determined by enzyme-linked immunosorbent assay
      (ELISA) and VV lectin-binding method. RESULTS: Cosmc mRNA expression and IgA1 O
      glycosylation level in IgAN patients was significantly lower than normal controls
      at baseline. Treatment of LPS could obviously inhibit Cosmc expression and
      increase the IgA1 secretion in peripheral B lymphocytes of IgAN patients, which
      resulted in a significantly increase in IgA1 aberrant glycosylation level.
      Addition of AMI could remarkably up regulated Cosmc expression, decrease IgA1
      secretion, and reverse glycosylation level in a dose related manner. CONCLUSION:
      AMI can up-regulate Cosmc expression of peripheral B lymphocytes and reverse IgA1
      aberrant O-glycosylation level, which might be the underlying mechanism of AMI
      therapy in treating IgAN. TRIAL REGISTRATION: TCTR20140515001 (Registration Date:
      2014-05-15).

PMID- 24942186
TI  - Maximum likelihood estimation for model Mt,alpha for capture-recapture data with
      misidentification.
AB  - We investigate model Mt,alpha  for abundance estimation in closed-population
      capture-recapture studies, where animals are identified from natural marks such
      as DNA profiles or photographs of distinctive individual features. Model Mt,alpha
      extends the classical model Mt  to accommodate errors in identification, by
      specifying that each sample identification is correct with probability alpha and
      false with probability 1-alpha. Information about misidentification is gained
      from a surplus of capture histories with only one entry, which arise from false
      identifications. We derive an exact closed-form expression for the likelihood for
      model Mt,alpha  and show that it can be computed efficiently, in contrast to
      previous studies which have held the likelihood to be computationally
      intractable. Our fast computation enables us to conduct a thorough investigation
      of the statistical properties of the maximum likelihood estimates. We find that
      the indirect approach to error estimation places high demands on data richness,
      and good statistical properties in terms of precision and bias require high
      capture probabilities or many capture occasions. When these requirements are not
      met, abundance is estimated with very low precision and negative bias, and at the
      extreme better properties can be obtained by the naive approach of ignoring
      misidentification error. We recommend that model Mt,alpha  be used with caution
      and other strategies for handling misidentification error be considered. We
      illustrate our study with genetic and photographic surveys of the New Zealand
      population of southern right whale (Eubalaena australis). 

PMID- 24942187
TI  - Evolutionarily conserved organization of the dopaminergic system in lamprey:
      SNc/VTA afferent and efferent connectivity and D2 receptor expression.
AB  - The dopaminergic system influences motor behavior, signals reward and novelty,
      and is an essential component of the basal ganglia in all vertebrates including
      the lamprey, one of the phylogenetically oldest vertebrates. The intrinsic
      organization and function of the lamprey basal ganglia is highly conserved. For
      instance, the direct and indirect pathways are modulated through dopamine D1 and
      D2 receptors in lamprey and in mammals. The nucleus of the tuberculum posterior,
      a homologue of the substantia nigra pars compacta (SNc)/ventral tegmental area
      (VTA) is present in lamprey, but only scarce data exist about its connectivity.
      Likewise, the D2 receptor is expressed in the striatum, but little is known about
      its localization in other brain areas. We used in situ hybridization and tracer
      injections, both in combination with tyrosine hydroxylase immunohistochemistry,
      to characterize the SNc/VTA efferent and afferent connectivity, and to relate its
      projection pattern with D2 receptor expression in particular. We show that most
      features of the dopaminergic system are highly conserved. As in mammals, the
      direct pallial (cortex in mammals) input and the basal ganglia connectivity with
      the SNc/VTA are present as part of the evaluation system, as well as input from
      the tectum as the evolutionary basis for salience/novelty detection. Moreover,
      the SNc/VTA receives sensory information from the olfactory bulbs, optic tectum,
      octavolateral area, and dorsal column nucleus, and it innervates, apart from the
      nigrostriatal pathway, several motor-related areas. This suggests that the
      dopaminergic system also contributes to the control of different motor centers at
      the brainstem level.

PMID- 24942189
TI  - Serum with phospholipase A2 receptor autoantibodies interferes with podocyte
      adhesion to collagen.
AB  - BACKGROUND: The majority of sera from patients with primary membranous
      nephropathy have autoantibodies against the M-type phospholipase A2 receptor
      (PLA2R) which is expressed on human podocytes. The rabbit variant of PLA2R
      attaches to collagen type IV via the fibronectin type II domain, which is also
      present in the human variant of PLA2R. DESIGN: To assess whether the human PLA2R
      variant is also involved in attachment to collagen type IV, we conducted a cell
      adhesion assay on a collagen-coated surface using PLA2R-transfected and mock
      transfected human embryonic kidney (HEK) cells. To test the hypothesis that sera
      from patients containing anti-PLA2R antibodies interfere with the adhesion of
      podocytes to collagen, we performed cell adhesion assays on a collagen type IV
      coated surface using positive and negative serum samples from patients and
      cultured human podocytes in vitro expressing PLA2R. RESULTS: The HEK cell
      adhesion assay confirmed an enhanced attachment of PLA2R-transfected cells to
      collagen type IV. We confirmed diminished podocyte adhesion in the presence of
      serum with anti-PLA2R antibodies. The concentration of anti-PLA2R antibodies
      correlated with proteinuria and to the degree of diminished adhesion of
      podocytes. CONCLUSIONS: We demonstrated that serum of patients containing
      autoantibodies directed to PLA2R interferes with the ability of podocytes to
      attach to collagen type IV in vitro, providing evidence of a serum soluble
      pathogenic factor interfering with podocyte adhesion in membranous nephropathy.

PMID- 24942188
TI  - Alcoholics have more tryptophan hydroxylase 2 mRNA and protein in the dorsal and
      median raphe nuclei.
AB  - BACKGROUND: Chronic alcohol use depletes brain serotonin (5-hydroxytryptamine [5
      HT]), yet we previously found more tryptophan hydroxylase 2 (TPH2), the rate
      limiting biosynthetic enzyme for 5-HT, in the dorsal raphe nucleus (DRN) of
      alcoholics. We sought to determine whether the increase in amount of TPH2 enzyme
      is associated with more TPH2 mRNA gene expression in the DRN of a new cohort of
      alcoholics and controls. METHODS: TPH2 mRNA and protein were measured by in situ
      hybridization and immunoautoradiography, respectively, in the DRN and median
      raphe nucleus (MRN) of age- and sex-matched pairs (n = 16) of alcoholics and
      nonpsychiatric controls. Alcohol use disorder diagnosis and medical, psychiatric,
      and family histories were obtained by psychological autopsy. Age and sex were
      covariates in the analyses. RESULTS: TPH2 mRNA in alcoholics was greater in the
      DRN and MRN compared to controls (DRN: controls: 3.6 +/- 1.6, alcoholics: 4.8 +/-
      1.8 nCi/mg of tissue, F = 4.106, p = 0.02; MRN: controls: 2.6 +/- 1.2,
      alcoholics: 3.5 +/- 1.1 nCi/mg of tissue, F = 3.96, p = 0.024). The difference in
      TPH2 mRNA was present in all DRN subnuclei (dorsal [DRd]: 135%, interfascicular
      [DRif]: 139%, ventral [DRv]: 135%, ventrolateral [DRvl]: 136% of control p <
      0.05) except the caudal subnucleus. Alcoholics also had more TPH2 protein in the
      DRN and MRN than controls (DRN: controls: 265 +/- 47, alcoholics: 318 +/- 47
      MUCi/g, F = 8.72, p = 0.001; MRN: controls: 250 +/- 33, alcoholics: 345 +/- 39
      MUCi/g, F = 7.78, p = 0.001). There is a positive correlation between TPH2
      protein and mRNA expression in the DRN (r = 0.815, p < 0.001), suggesting that
      the higher amount of TPH2 protein is due to an increase in TPH2 gene expression.
      CONCLUSIONS: These findings suggest that greater TPH2 gene expression is the
      basis for more TPH2 protein in the DRN and MRN in alcoholics.

PMID- 24942190
TI  - Bringing them together: plasmid pMV158 rolling circle replication and conjugation
      under an evolutionary perspective.
AB  - Rolling circle-replicating plasmids constitute a vast family that is particularly
      abundant in, but not exclusive of, Gram-positive bacteria. These plasmids are
      constructed as cassettes that harbor genes involved in replication and its
      control, mobilization, resistance determinants and one or two origins of lagging
      strand synthesis. Any given plasmid may contain all, some, or just only the
      replication cassette. We discuss here the family of the promiscuous streptococcal
      plasmid pMV158, with emphasis on its mobilization functions: the product of the
      mobM gene, prototype of the MOBV relaxase family, and its cognate origin of
      transfer, oriT. Amongst the subfamily of MOBV1 plasmids, three groups of oriT
      sequences, represented by plasmids pMV158, pT181, and p1414 were identified. In
      the same subfamily, we found four types of single-strand origins, namely ssoA,
      ssoU, ssoW, and ssoT. We found that plasmids of the rolling-circle Rep_2 family
      (to which pMV158 belongs) are more frequently found in Lactobacillales than in
      any other bacterial order, whereas Rep_1 initiators seemed to prefer hosts
      included in the Bacillales order. In parallel, MOBV1 relaxases associated with
      Rep_2 initiators tended to cluster separately from those linked to Rep_1
      plasmids. The updated inventory of MOBV1 plasmids still contains exclusively
      mobilizable elements, since no genes associated with conjugative transfer (other
      than the relaxase) were detected. These plasmids proved to have a great
      plasticity at using a wide variety of conjugative apparatuses. The promiscuous
      recognition of non-cognate oriT sequences and the role of replication origins for
      lagging-strand origin in the host range of these plasmids are also discussed. 

PMID- 24942191
TI  - An elasto-mechanical unfeelability cloak made of pentamode metamaterials.
AB  - Metamaterial-based cloaks make objects different from their surrounding appear
      just like their surrounding. To date, cloaking has been demonstrated
      experimentally in many fields of research, including electrodynamics at microwave
      frequencies, optics, static electric conduction, acoustics, fluid dynamics,
      thermodynamics and quasi two-dimensional solid mechanics. However, cloaking in
      the seemingly simple case of three-dimensional solid mechanics is more demanding.
      Here, inspired by invisible core-shell nanoparticles in optics, we design an
      approximate elasto-mechanical core-shell 'unfeelability' cloak based on pentamode
      metamaterials. The resulting three-dimensional polymer microstructures with
      macroscopic overall volume are fabricated by rapid dip-in direct laser writing
      optical lithography. We quasi-statically deform cloak and control samples in the
      linear regime and map the displacement fields by autocorrelation-based analysis
      of recorded movies. The measured and the calculated displacement fields show very
      good cloaking performance. This means that one can elastically hide objects along
      these lines. 

PMID- 24942192
TI  - Influence of hospital volume on outcomes of laparoscopic gastrectomy for gastric
      cancer in patients with comorbidity in Japan.
AB  - OBJECTIVE: Little information is available on the relationship between hospital
      volume and the outcomes of laparoscopic gastrectomy for gastric cancer in
      patients with comorbidity. This study aimed to investigate the influence of
      hospital volume on patient outcomes of laparoscopic gastrectomy for gastric
      cancer in patients with comorbidity using a national administrative database.
      METHODS: A total of 5941 comorbid patients treated with laparoscopic gastrectomy
      for gastric cancer were referred to 741 hospitals in Japan. We collected
      patients' data from the administrative database to compare laparoscopy-related
      complications, in-hospital mortality, length of stay (LOS), and medical costs
      during hospitalization in relation to hospital volume. Hospital volume was
      categorized into two groups: low (<40 cases in 3 years; n = 4111) and high (>= 40
      cases; n = 1830). RESULTS: There were no significant differences between the
      groups in laparoscopy-related complications and in-hospital mortality (p = 0.684
      and p = 0.200, respectively). However, significant variations in mean LOS and
      medical costs were observed between hospital volume categories (26.1 days vs.
      20.2 days and 16,163.9 US dollars vs. 14,345.9 US dollars, respectively; p <
      0.001). Multiple linear regressions revealed that higher hospital volume was
      significantly associated with shorter LOS and lower medical costs during
      hospitalization. The unstandardized coefficient for LOS was -4.62 days (95%
      confidence interval = -5.63--3.60, p < 0.001), whereas that for medical costs was
      -1424.1 US dollars (95% confidence interval = -1962.5--885.6, p < 0.001).
      CONCLUSION: Hospital volume was significantly associated with a decrease of LOS
      and medical costs of comorbid patients undergoing laparoscopic gastrectomy for
      gastric cancer.

PMID- 24942193
TI  - Modified prepuce unfurling for buried penis: a report of 12 years of experience.
AB  - BACKGROUND/OBJECTIVE: About 10 years ago, we started to correct buried penis
      using the technique of modified prepuce unfurling. We have made modifications in
      the years since our preliminary results were reported in 2002. METHODS: One
      hundred and thirty-four patients received modified prepuce unfurling since 2000,
      with ages ranging from 2 months to 33 years. The surgical procedures included the
      removal of the narrowest part of the prepuce, dissection of the fibrotic tissue
      from the Buck's fascia, and unfurling the inner prepuce to cover the penis. Most
      patients had their procedures in day care service. No urinary catheter was
      needed. All patients were followed up for at least 2 months. RESULTS: Most
      patients had satisfactory results. All patients had the glans exposed after
      surgery, although one patient needed reoperation for prolonged edema and two
      patients had wound infections. CONCLUSION: Modified prepuce unfurling is a safe
      and effective method to correct buried penis.

PMID- 24942194
TI  - Dexamethasone combined with other antiemetics for prophylaxis after laparoscopic
      cholecystectomy.
AB  - BACKGROUND/OBJECTIVE: Postoperative nausea and vomiting (PONV) is one of the most
      common and distressing adverse events after laparoscopic cholecystectomy (LC). A
      meta-analysis of randomized clinical trials (RCTs) was performed to determine the
      efficacy and safety of dexamethasone combined with other antiemetic in the
      prevention of PONV in patients undergoing LC. METHODS: A systematic literature
      search was conducted to identify all relevant RCTs. The primary outcome was PONV
      in the early period (0-3 hours, 0-4 hours, or 0-6 hours), late period (>6 hours),
      and the overall period (0-24 hours). RESULTS: Nine RCTs with a total of 1089
      patients were included in the analysis. Pooled analysis showed that dexamethasone
      combined with other antiemetics provided significantly better prophylaxis than
      single antiemetics in the early period [odds ratio (OR): 0.34; 95% confidence
      interval (CI): 0.21-0.55; p < 0.001], late period (OR: 0.35; 95% CI: 0.22-0.57; p
      < 0.001), and the overall period (OR: 0.36; 95% CI: 0.27-0.49; p < 0.001).
      Correspondingly, rescue antiemetic usage was significantly less in the
      combination therapy group (OR: 0.22; 95% CI: 0.12-0.41; p < 0.001). The most
      frequently reported adverse events were headache, dizziness, and itching. The
      incidence of adverse events did not differ between the two groups. CONCLUSION:
      Dexamethasone combined with other antiemetics was significantly better than
      single antiemetics for prophylaxis of PONV in patients undergoing LC, without
      apparent side effects.

PMID- 24942196
TI  - The novel PI3 kinase inhibitor, BAY 80-6946, impairs melanoma growth in vivo and
      in vitro.
AB  - Due to its almost universal resistance to chemotherapy, metastasized melanoma
      remains a major challenge in clinical oncology. Given that phosphatidyl inositol
      3 kinase (PI3K) activation in melanoma cells is associated with poor prognosis,
      disease progression and resistance to chemotherapy, the PI3K-Akt signalling
      pathway is a promising therapeutic target for melanoma treatment. We analysed six
      human melanoma cell lines for their constitutive activation of Akt and then
      tested two representative lines, A375 and LOX, for their susceptibility to PI3K
      inhibition by the highly specific small molecule inhibitor, BAY 80-6946. In
      addition, the effect of BAY 80-6946 on A375 and LOX melanoma cells was assessed
      in vivo in a xenotransplantation mouse model. We provide experimental evidence
      that specifically inhibiting the PI3K pathway and phosphorylation of Akt by this
      novel compound results in antitumoral activities including inhibition of
      proliferation, induction of apoptosis and cell cycle arrest in vitro and in vivo.
      However, the susceptibility did not show a clear-cut pattern and differed between
      the melanoma cell lines tested, resulting in in vivo growth inhibition of A375
      but not LOX melanoma cells. Thus, in some cases BAY 80-6946 or related compounds
      may be a valuable addition to the therapeutic armamentarium. 

PMID- 24942197
TI  - Molecular recognition with nanostructures fabricated by photopolymerization
      within metallic subwavelength apertures.
AB  - The first demonstration of fabrication of submicron lateral resolution
      molecularly imprinted polymer (MIP) patterns by photoinduced local polymerization
      within metal subwavelength apertures is reported. The size of the
      photopolymerized MIP features is finely tuned by the dose of 532 nm radiation.
      Rhodamine 123 (R123) has been selected as a fluorescent model template to prove
      the recognition capability of the MIP nanostructures, which has been evaluated by
      fluorescence lifetime imaging microscopy (FLIM) with single photon timing
      measurements. The binding selectivity provided by the imprinting effect has been
      confirmed in the presence of compounds structurally related to R123. These
      results pave the way to the development of nanomaterial architectures with
      biomimetic artificial recognition properties for environmental, clinical and food
      testing. 

PMID- 24942199
TI  - Quaternary ammonium and phosphonium based ionic liquids: a comparison of common
      anions.
AB  - A series of ammonium-based ionic liquids and their phosphonium analogues have
      been investigated using X-ray Photoelectron Spectroscopy (XPS). A robust C 1s
      peak fitting model has been developed and described for the tetraalkylphosphonium
      and tetraalkylammonium families of ionic liquid, with comparisons made between
      the two series. Cation-anion interactions have been investigated to determine the
      impact of changing the cationic core from nitrogen to phosphorus upon the
      electronic environment of the anion. Comparisons between long and short chain
      cationic systems are also described. 

PMID- 24942198
TI  - Risk-adjusted clinical outcomes in patients enrolled in a bloodless program.
AB  - BACKGROUND: Although clinical outcomes have been reported for patients who do not
      accept allogeneic blood transfusion (ABT), many previous studies lack a control
      group, fail to use risk adjustment, and focus exclusively on cardiac surgery.
      STUDY DESIGN AND METHODS: We report a risk-adjusted, propensity score-matched,
      retrospective case-control study of clinical outcomes for inpatients who did not
      accept ABT (bloodless, n = 294) and those who did accept ABT (control, n = 1157).
      Multidisciplinary specialized care was rendered to the bloodless patients to
      conserve blood and optimize clinical outcomes. Differences in hemoglobin (Hb),
      mortality, five morbid outcomes, and hospital charges and costs were compared.
      Subgroups of medical and surgical patients were analyzed, and independent
      predictors of outcome were determined by multivariate analysis. RESULTS: Overall,
      mortality was lower in the bloodless group (0.7%) than in the control group
      (2.7%; p = 0.046), primarily attributed to the surgical subgroup. After risk
      adjustment, bloodless care was not an independent predictor of the composite
      adverse outcome (death or any morbid event; p = 0.91; odds ratio, 1.02; 95%
      confidence interval, 0.68-1.53). Discharge Hb concentrations were similar in the
      bloodless (10.8 +/- 2.7 g/dL) and control (10.9 +/- 2.3 g/dL) groups (p = 0.42).
      Total and direct hospital costs were 12% (p = 0.02) and 18% (p = 0.02) less,
      respectively, in the bloodless patients, a difference attributed to the surgical
      subgroup. CONCLUSIONS: Using appropriate blood conservation measures for patients
      who do not accept ABT results in similar or better outcomes and is associated
      with equivalent or lower costs. This specialized care may be beneficial even for
      those patients who accept ABT.

PMID- 24942200
TI  - Melatonin promotes the acquisition of neural identity through extracellular
      signal-regulated kinases 1/2 activation.
AB  - Melatonin, a major pineal secretory product, exerts a range of physiological and
      neuroprotective effects. However, the functional significance of melatonin in
      determining neural identity, and the mechanisms by which this may occur, is
      unknown. In this study, P19 cells were used as a model system and cell behavior
      was monitored. Our data show that melatonin plays an important role in
      determining cell fate during neural commitment and promoting the differentiation
      of pluripotent P19 cells (Oct4(+) Sox2(+) ) into neural stem cells (Oct4(-)
      Sox2(+) ). This promotion appears to coincide with the activation of the MT1
      receptor and phosphorylation of extracellular-signal-regulated kinases 1/2
      (ERK1/2). Furthermore, our results show that melatonin regulates neural fate
      specification of P19 cells through two distinct mechanisms: the promotion of
      nuclear localization of ERK1/2 and upregulation of Sox2 transcription, and
      suppression of Smad1-induced expression of mesodermal-specific genes, such as
      Bra. 

PMID- 24942201
TI  - Silver lining in the dark cloud of aneurysm disease.
AB  - An ascending aortic aneurysm is a common and very much unwelcome diagnosis that
      has never been associated with anything positive. We believe, however, that there
      actually is a silver lining to this disease: aortic root and ascending aortic
      aneurysms actually protect against atherosclerosis. We have found that patients
      with ascending aneurysms have both decreased arterial calcification and carotid
      intima-media thickness, late and early indicators of atherosclerosis,
      respectively. In addition to these clinical data, we also found data regarding
      molecular mechanisms, genetic studies, and pharmacologic evidence that
      corroborate our clinical findings, in particular, evidence regarding matrix
      metalloproteinases and transforming growth factor-beta pathways. In this article,
      we lay out the evidence that has been accruing for the protective effect of
      ascending aneurysms against atherosclerosis.

PMID- 24942202
TI  - Management and outcomes of single subsegmental pulmonary embolus: a retrospective
      audit at North Shore Hospital, New Zealand.
AB  - BACKGROUND: It is unknown whether filling defects in subsegmental arteries on
      multidetector computed tomography pulmonary angiography correlate with clinically
      relevant subsegmental pulmonary embolism (PE) on pulmonary angiography. Current
      guidelines do not differentiate between PE in segmental and subsegmental vessels,
      and many patients receive at least 3 months anticoagulation. The strategy
      employed at North Shore Hospital in haemodynamically stable patients with single
      subsegmental PE is to perform bilateral lower leg compression ultrasound (CUS).
      Anticoagulation is withheld if CUS is negative; a bilateral CUS is repeated in 7
      10 days. AIM: The aim of this retrospective audit was to ensure our current
      management strategy is safe. METHODS: All diagnoses of single subsegmental PE
      between June 2005 and June 2013 were included. The primary outcome was the rate
      of venous thromboembolism (VTE) recurrence within 3 months of single subsegmental
      PE diagnosis. Secondary outcomes were rates of major/minor bleeding and all-cause
      mortality. RESULTS: Thirty-two patients were included - 20 were treated with
      anticoagulation; 12 were managed with observation/serial bilateral lower limb
      CUS. None of the patients in either group had VTE recurrence by 3 months. No
      bleeding episodes were observed in the observation group; there was a 10% major
      bleeding rate (n = 2) in the treatment group. One death occurred in each group,
      neither of which was attributed to VTE. CONCLUSION: Withholding anticoagulation
      in patients with single subsegmental PE and negative serial bilateral CUS appears
      to be a safe and effective management strategy, with a low risk of VTE
      recurrence.

PMID- 24942203
TI  - Comorbidities and health-related quality of life in Spanish patients with
      moderate to severe psoriasis: a cross-sectional study (Arizona study).
AB  - Psoriasis is a common, chronic inflammatory immunologically mediated disease of
      the skin, showing a high prevalence of associated comorbidities, and strongly
      affecting patients' health-related quality of life (HR-QOL), with profound impact
      on the psychological aspect. We aimed to establish the correlation between HR-QOL
      and the associated comorbidities in patients with moderate to severe psoriasis in
      Spain. A cross-sectional, observational, epidemiological study was conducted at
      68 dermatology-based centers across Spain. From October 2010 to June 2011, all
      adult patients diagnosed with moderate to severe psoriasis at least 6 months
      prior to the study visit and receiving or not receiving treatment for psoriasis
      were eligible for inclusion. A total of 1022 patients were included. The study
      population showed mean 36-item short-form (SF-36) physical and mental health
      scores and Dermatological Life Quality Index (DLQI) of 49.7, 46.2 and 5.3,
      respectively. The multiple linear regression models showed that patients with
      moderate to severe psoriasis and a diagnosis of psoriatic arthritis (PsA),
      hypertension, diabetes mellitus, sleep disturbances or obesity were found to have
      lower SF-36 health physical scores. Female patients with depression or anxiety
      disorders had lower SF-36 health mental scores. Patients diagnosed with moderate
      to severe psoriatic disease and associated anxiety disorder had greater DLQI
      scores. Moderate to severe psoriasis has a significant burden on the HR-QOL of
      patients. Regardless of sex, patients with several comorbidities such as PsA,
      hypertension or obesity were found to have worse scores in the physical component
      of the QOL questionnaire, whilst women were more affected in the mental health
      component than men. 

PMID- 24942204
TI  - Sequence-specific DNA alkylation by tandem Py-Im polyamide conjugates.
AB  - Tandem N-methylpyrrole-N-methylimidazole (Py-Im) polyamides with good sequence
      specific DNA-alkylating activities have been designed and synthesized. Three
      alkylating tandem Py-Im polyamides with different linkers, which each contained
      the same moiety for the recognition of a 10 bp DNA sequence, were evaluated for
      their reactivity and selectivity by DNA alkylation, using high-resolution
      denaturing gel electrophoresis. All three conjugates displayed high reactivities
      for the target sequence. In particular, polyamide 1, which contained a beta
      alanine linker, displayed the most-selective sequence-specific alkylation towards
      the target 10 bp DNA sequence. The tandem Py-Im polyamide conjugates displayed
      greater sequence-specific DNA alkylation than conventional hairpin Py-Im
      polyamide conjugates (4 and 5). For further research, the design of tandem Py-Im
      polyamide conjugates could play an important role in targeting specific gene
      sequences.

PMID- 24942205
TI  - Oral vancomycin might be useful to suppress enteral VRE load: a conceptual
      experiment.

PMID- 24942206
TI  - Content, accuracy and completeness of patient consent in a regional vascular
      surgery unit.
AB  - OBJECTIVE: Although the General Medical Council has published guidelines for
      procedural consent, there is evidence to suggest that deficiencies still occur in
      completion demographics, documentation of procedural risks and information
      regarding alternative therapies. We assessed the accuracy and completeness of
      vascular consent within our unit. METHODS: A retrospective review of patients
      undergoing vascular intervention between February 2010 and 2011 was performed.
      Patient chart examination included the analysis of consenting doctors' grade,
      responsible vascular consultant, completeness of procedural entry, documentation
      of correct side, use of abbreviations, discussion of benefits and complications,
      additional information and overall legibility. RESULTS: 323 patient consent forms
      were reviewed (male 203, mean age 68.0 years, elective surgery 241) including 50
      AAA repairs, 27 carotid endarterectomies, 88 peripheral arterial reconstructions,
      96 amputations and 69 elective varicose vein surgeries. 294 (91%) consent forms
      were completed by a specialist registrar or above with 286 (88.5%) forms having
      the responsible consultant documented. 85.4% of patients were consented within 48
      h of surgery. 245 (75.9%) consent forms had legible printed names. However, only
      75 (23.2%) had a legible signature. 306 (94.7%) consent forms had the procedure
      documented in full but 165 (51.0%) had used abbreviations. 103 (31.9%) had
      documentation of the intended benefits of surgery whilst 293 (90.7%) had
      documentation of potential complications. Three patients had documented evidence
      of receiving written information and one patient received a copy of the consent
      form. Of those surveyed, procedural mortality was discussed in 62.5% of open and
      47.3% of endovascular AAA repairs. Stroke was documented in 96.3% of consent
      forms for carotid endarterectomy. Scarring was included most commonly in patients
      undergoing venous procedures. CONCLUSION: Vascular consent is a complex process
      involving a number of discussions and meetings with patients. Our unit has
      demonstrated compliance of nearly 90% for all consent-related processes and
      remains consistent with current GMC guidance. However, further improvement
      including the documentation of intended benefits, provision of additional written
      information whilst reducing the use of abbreviations is desired.

PMID- 24942208
TI  - Fibroblast growth factor 20 (FGF20) gene polymorphism and risk of Parkinson's
      disease: a meta-analysis.
AB  - Fibroblast growth factor 20 (FGF20) widely expressed in the substantia nigra is a
      neurotrophic factor and enhances the survival of midbrain dopaminergic neurons.
      Genetic association between variants in FGF20 gene (rs1721100) and PD has been
      reported, however, the results have been conflicting. A total of 3,463 PD
      patients and 4,606 controls from 5 case-control studies, which were identified by
      searching Web of Science, Embase and PubMed database up to March 2014, were
      collected for this meta-analysis. The meta-analysis showed an association between
      FGF20 gene rs1721100 polymorphism and risk of Parkinson's disease under a
      recessive model (GG versus CG+GG; OR = 1.15, 95 % CI 1.02-1.29, p = 0.02) but not
      under a dominant model (CG+GG versus CC; OR = 1.03, 95 % CI 0.93-1.13, p = 0.57).
      These findings suggest that rs1721100 GG genotype within FGF20 gene is a risk
      factor for PD. To our knowledge, this is the first meta-analysis to access to the
      association of FGF20 gene rs1721100 polymorphism with PD risk.

PMID- 24942207
TI  - Refractory warm IgM-mediated autoimmune hemolytic anemia associated with Churg
      Strauss syndrome responsive to eculizumab and rituximab.

PMID- 24942209
TI  - Dual-modal MRI contrast agent with aggregation-induced emission characteristic
      for liver specific imaging with long circulation lifetime.
AB  - We herein report a novel dual-modal MRI contrast agent, TPE-2Gd, for both
      magnetic and fluorescence imaging. TPE-2Gd consists of a hydrophobic
      tetraphenylethene (TPE) fluorophore and two hydrophilic gadolinium (Gd)
      diethylenetriaminepentaacetic acid moieties. As an amphiphilic molecule, TPE-2Gd
      aggregates into micelles at a high concentration in aqueous medium. These
      aggregates are highly emissive, showing an aggregation-induced emission (AIE)
      characteristic. TPE-2Gd is used as a fluorescent agent for cell imaging, which
      demonstrates negligible cytotoxicity and excellent photostability owing to its
      AIE property. As a magnetic resonance imaging (MRI) contrast agent, TPE-2Gd
      exhibits similar longitudinal relaxivity in water (R1,TPE-2Gd = 3.36 +/- 0.10 s(
      1) per mM of Gd(3+)) as those commercial agents (e.g., Magnevist, R1,magnevist =
      3.70 +/- 0.02 s(-1) per mM of Gd(3+)). Compared with Magnevist, the circulation
      lifetime of TPE-2Gd nanoaggregates in living rats is extended from 10 min to 1 h.
      With relatively high specificity to the liver, the MR imaging could remain
      hyperintense in liver even after 150 min post injection. These TPE-2Gd
      nanoparticles can be excreted gradually via renal filtration due to the
      disassembly of the nanoparticles into small molecules during circulation. TPE-2Gd
      could thus potentially be used as a liver specific MRI contrast agent for
      clinical diagnosis. 

PMID- 24942211
TI  - Reduce dimension or reduce weights? Comparing two approaches to multi-arm studies
      in network meta-analysis.
AB  - Network meta-analysis is a statistical method combining information from
      randomised trials that compare two or more treatments for a given medical
      condition. Consistent treatment effects are estimated for all possible treatment
      comparisons. For estimation, weighted least squares regression that in a natural
      way generalises standard pairwise meta-analysis can be used. Typically, as part
      of the network, multi-arm studies are found. In a multi-arm study, observed
      pairwise comparisons are correlated, which must be accounted for. To this aim,
      two methods have been proposed, a standard regression approach and a new approach
      coming from graph theory and based on contrast-based data (Rucker 2012). In the
      standard approach, the dimension of the design matrix is appropriately reduced
      until it is invertible ('reduce dimension'). In the alternative approach, the
      weights of comparisons coming from multi-arm studies are appropriately reduced
      ('reduce weights'). As it was unclear, to date, how these approaches are related
      to each other, we give a mathematical proof that both approaches lead to
      identical estimates. The 'reduce weights' approach can be interpreted as the
      construction of a network of independent two-arm studies, which is basically
      equivalent to the given network with multi-arm studies. Thus, a simple random
      effects model is obtained, with one additional parameter for a common
      heterogeneity variance. This is applied to a systematic review in depression.

PMID- 24942215
TI  - [Femtosecond laser-assisted cataract surgery. A rapidly developing operation
      met].

PMID- 24942210
TI  - Lower exposure and faster clearance of bevacizumab in gastric cancer and the
      impact of patient variables: analysis of individual data from AVAGAST phase III
      trial.
AB  - Altered pharmacokinetics of antibody drugs has been reported in advanced gastric
      cancer (AGC). We aim to evaluate bevacizumab pharmacokinetics in AGC from the
      Phase III trial (AVAGAST), and explore the influence of patient variables.
      Bevacizumab concentrations (Cp) were measured in plasma samples taken following
      disease progression from 162 patients (7.5 mg/kg every 3 weeks). Predicted Cp
      [median and 90% prediction interval] was simulated using the population
      pharmacokinetic model established for other cancers (PPK model) and compared to
      observed Cp. Bevacizumab clearance was estimated using NONMEM and compared
      between subgroups. Patient characteristics of AGC are similar to other cancers
      except for lower body weight despite higher percentage of males. Eighty-five
      percent of observed Cp was below the median predicted Cp and 38% below the lower
      boundary of the 90% prediction interval. Median bevacizumab clearance in AGC was
      4.5 versus 3 mL/day/kg in other cancers. Bevacizumab clearance was significantly
      faster (p < 0.05) in patients without gastrectomy (n = 42) or lower albumin.
      Clearance appeared to be faster in patients with lower total protein, higher ECOG
      scores, more metastatic sites, and poorer response. No significant difference in
      bevacizumab concentrations and clearance was observed between Asian and Non-Asian
      patients. AGC patients exhibited significantly lower bevacizumab exposure due to
      an approximate 50% increase in clearance versus other cancers. Bevacizumab is
      cleared faster in patients without prior gastrectomy. No significant difference
      in bevacizumab pharmacokinetics was observed between Asian and Non-Asian
      patients. The underlying mechanism for faster bevacizumab clearance in AGC is
      unknown and warrants further research.

PMID- 24942216
TI  - [Pattern laser trabeculoplasty and argon laser trabeculoplasty for treatment of
      glaucoma].
AB  - INTRODUCTION: Argon laser trabeculoplasty (ALT) and pattern laser trabeculoplasty
      (PLT) are two laser surgery methods for treatment of open angle glaucoma and the
      effect in reducing intraocular pressure (IOP) of these methods was compared in a
      retrospective study. METHODS: The IOP, the best corrected visual acuity (BCVA)
      and the eye drop glaucoma medication used by patients who were treated by ALT or
      PLT in this clinic between January 2011 and December 2012 were compiled and
      evaluated. RESULTS: An ALT was carried out on 22 eyes from 22 patients (13 right
      and 9 left eyes in patients with an average age of 71.1 +/- 1.5 years, 7 men and
      15 women) and a significant average reduction of IOP from 18.6 +/- 0.9 to 15.3 +/
      0.7 mmHg (p < 0.001) was observed an average of 8.2 +/- 0.8 weeks after ALT. The
      number of dropped glaucoma medications per eye (p = 0.19) and the mean BCVA both
      remained constant (p = 0.15). A PLT was carried out on 20 eyes from 20 patients
      (12 right and 8 left eyes in patients with an average age of 69.9 +/- 2.6 years,
      10 men and 10 women) and a significant average reduction of IOP from 20.2 +/- 1.1
      to 15.6 +/- 0.8 mmHg (p < 0.001) was observed an average of 8.3 +/- 0.6 weeks
      after PLT. The number of dropped glaucoma medications per eye (p = 0.08) and the
      mean BCVA both remained constant (p = 0.59). The difference in the reduction of
      IOP between the ALT and PLT groups was not significant (p=0.26). CONCLUSION: Both
      PLT and ALT are effective methods for treatment of open angle glaucoma and lead
      to similar significant reductions in IOP.

PMID- 24942217
TI  - [Web-based analysis of Stilling's color plates].
AB  - BACKGROUND: Color vision tests with pseudoisochromatic plates currently represent
      the most common procedure for the screening of congenital color vision
      deficiencies. By means of a web-based color vision test, new and old color plates
      can be tested for diagnostic quality without major effort. METHODS: A total of 16
      digitized Stilling's color plates of the 11th edition from 1907 were included in
      a web-based color vision test (http://www.farbsehtest.de). The chi(2)-test was
      used to check whether the Stilling color plates showed similar results to the
      nine previously evaluated Ishihara color plates. RESULTS: A total of 518 subjects
      including101 (19.5 %) female subjects with a mean age of 34.6 +/- 17 years, took
      the web-based test with the 25 plates. For all participants the range for the
      correctly recognized plates was between 5.2 % (n = 27) and 97.7 % (n = 506) for
      the Stilling color plates and between 64.9 % (n = 336) and 100 % (n = 518) for
      the Ishihara color plates. For participants with more than 5 errors (n = 247),
      the range for correctly recognized plates was between 2.0 % (n = 5) and 98.0 % (n
      = 242) for the Stilling plates and between 42.5 % (n = 105) and 100 % (n = 247)
      for the Ishihara plates. Taking all color plates and all participants into
      account there was a significantly higher incidence of erroneous recognition of
      the Stilling color plates (3038 false and 5250 true answers) compared to the
      Ishihara color plates (1511 false and 3151 true answers) (p < 0.001, chi(2)
      test). CONCLUSION: The diagnostic quality of the tested Stilling color pates was
      very variable. Some of the plates could be used for the test edition of the
      Velhagen/Broschmann/Kuchenbecker color plates from 2014. Overall, the Stilling
      color plates were recognized with a higher incidence of error by all participants
      in the web-based test compared to the utilized Ishihara color plates, which in
      most cases was attributable to ambiguity of some symbols.

PMID- 24942218
TI  - [A 16-year-old female patient with massive bilateral blepharedema].
AB  - CASE REPORT: A 16-year-old female patient initially presented with bilateral
      swelling and redness of the eyelids already existing for the duration of two
      days. The symptoms had started after the patient dyed her eyelashes and eyebrows
      with henna. THERAPY: Systemic antihistamine and glucocorticoid therapy led to no
      visible improvement. An intravenous antibiotic treatment was started which
      resolved the symptoms entirely. CONCLUSION: The diagnosis of an allergic contact
      dermatitis with a secondary bacterial infection was made.

PMID- 24942219
TI  - [Vitreous body and retinal vein occlusion].
AB  - PURPOSE: The aim of this study was to evaluate whether the adhesion status of the
      posterior vitreous cortex (PVC) towards the internal limiting membrane (ILM) has
      an impact on the development of retinal vein occlusion (RVO). MATERIAL AND
      METHODS: In a retrospective analysis the operation protocols of 238 eyes
      receiving pars plana vitrectomy (ppV) and radial optic neurotomy (RON) for
      central retinal vein occlusion (CRVO) or ppV in combination with arteriovenous
      sheathotomy (AVS) for branch retinal vein occlusion (BRVO) were evaluated with
      respect to the intraoperative status of posterior vitreous body adhesion. The
      results were compared with age-matched healthy controls. RESULTS: In this study
      145 eyes (60.9 %) suffering from CRVO and 93 eyes (39.1 %) diagnosed with BRVO
      were included. In eyes with CRVO and BRVO the posterior vitreous cortex (PVC) was
      significantly more often attached (126 eyes, 86.9 % and 89 eyes, 95.7 %,
      respectively) than completely detached (19 eyes, 13.1 % and 4 eyes, 4.3 %,
      respectively, in each case p < 0.001). In the age groups between 70 and 79 years
      as well as between 80 and 89 years the PVC was significantly more often attached
      in both RVO entities in comparison to age-matched healthy controls (CRVO 70-79
      years, p = 0.001 and 80-89 years, p = 0.002 and BRVO 70-79 years, p < 0.001, 80
      89 years, p = 0.011). In eyes from the age group between 65 and 69 years (of age)
      the PVC was not significantly more often attached in comparison to healthy
      controls (CRVO p = 0.334 and BRVO p = 0.114). CONCLUSION: According to these
      findings posterior vitreous adhesion is an independent risk factor for the
      development of retinal vein occlusion among patients aged 70 years or older.

PMID- 24942220
TI  - [Ophthalmomyiasis externa].
AB  - Ophthalmomyiasis refers to infestation of the eye by fly larvae. Although rare,
      cases have been reported from all over the world. Patients with ophthalmomyiasis
      suffer from itching, foreign body sensation and epiphora. Ophthalmomyiasis is
      mostly caused by larvae of Oestrus ovis, the common sheep botfly. Larvae of
      Oestrus ovis are photophobic and hide in the upper and lower fornix. First line
      treatment consists of mechanical removal of the larvae. 

PMID- 24942221
TI  - [Complement activation after induction of ocular hypertension in an animal
      model].
AB  - BACKGROUND: Although an elevated intraocular pressure (IOP) is known as the main
      risk factor for glaucoma, many studies also showed an involvement of the immune
      system in this disease. In this study we investigated if a moderate increase in
      IOP leads to activation of the complement system. METHODS: The IOP was elevated
      experimentally in the left eye of rats, whereas the fellow eye served as the
      control. The IOP was measured at regular intervals. The number of retinal
      ganglion cells (RGC) was quantified via NeuN staining. To evaluate the activation
      of the complement system staining for C3, membrane attack complex (MAC), and
      mannose-binding lectin (MBL) was performed. Furthermore, we investigated possible
      glia activation (GFAP and vimentin) and apoptosis (Bax). RESULTS: A moderate
      elevation of the IOP was noted from day 11 after induction of ocular hypertension
      (OHT) until the end of the study (28 days, p = 0.0005). In the OHT-group
      significantly fewer RGCs (p = 0.02) were detected. Additionally, we noted
      significant C3 and MAC activation in the ganglion cell layer (C3, p = 0.001 and
      MAC, p = 0.02) as well as in the total retina (C3, p = 0.002 and MAC, p = 0.012).
      An activation via the lectin pathway by MBL staining could not be detected (p =
      0.40). At this point in time no alterations with regard to glia cells were noted
      (GFAP, p = 0.97 and vimentin, p = 0.99). No apoptosis via Bax pathway could be
      observed (p = 0.90). CONCLUSION: The results suggest that the complement system
      is involved in the loss of RGCs even by a moderate IOP elevation which was
      indicated by significantly more C3 and MAC depositions in the OHT group.

PMID- 24942223
TI  - Efficacy and safety of functional electrical stimulation of lower limb muscles in
      elderly patients with chronic heart failure: A pilot study.
AB  - BACKGROUND: Exercise training is an established modality in chronic heart
      failure. Functional electrical stimulation (FES) is an effective alternative mode
      of training in patients unwilling or unable to exercise; however, it has not been
      investigated in elderly patients. We sought to investigate the effects of FES on
      functional status, quality of life, emotional status and endothelial function in
      chronic heart failure patients aged 70 years or higher. METHODS: Thirty patients
      with stable systolic chronic heart failure (mean age 75 +/- 3 years, New York
      Heart Association (NYHA) class II/III, 37%/63%) randomly underwent a six-week FES
      training programme or placebo. Questionnaires addressing quality of life (Kansas
      City Cardiomyopathy Questionnaire (KCCQ), functional and overall) and emotional
      stress (Zung self-rating depression scale (SDS), Beck Depression Inventory
      (BDI)), as well as endothelial function (flow-mediated dilatation) were assessed
      at baseline and upon protocol completion. RESULTS: A significant improvement in
      NYHA class (p=0.005), KCCQ-functional (F=68.6, p for interaction<0.001), KCCQ
      overall (F=66.9, p<0.001), BDI (F=66.3, p<0.001) and Zung SDS (F=95.1, p<0.001)
      was observed in the FES group compared to placebo. Patients in the FES group also
      had a significant increase in flow-mediated dilatation compared with placebo
      (F=59.1, p<0.01). FES-induced per cent change in flow-mediated dilatation was
      significantly correlated with respective per cent change in KCCQ functional
      (r=0.386, p=0.039). CONCLUSION: In this pilot study, FES effectively improved
      functional status, quality of life, motional stress and endothelial function in
      elderly chronic heart failure patients and warrants further investigation in this
      particular group of patients.

PMID- 24942224
TI  - Socioeconomic factors and use of secondary preventive therapies for
      cardiovascular diseases in South Asia: The PURE study.
AB  - OBJECTIVE: The purpose of this study was to determine the association of
      socioeconomic factors on use of cardioprotective medicines in known coronary
      heart disease (CHD) or stroke in South Asia. METHODS: We enrolled 33,423 subjects
      aged 35-70 years (women 56%, rural 53%, low education 51%, low household wealth
      25%) in 150 communities in India, Pakistan and Bangladesh during 2003-2009.
      Information regarding socioeconomic status, disease conditions and treatments was
      recorded. We studied influence of rural location, educational status and
      household wealth on use of drug therapies. Odds ratios (ORs) and 95% confidence
      intervals were calculated. RESULTS: CHD was reported in 683 (2.0%), stroke 316
      (0.9%), and CHD/stroke in 970 (2.9%). Median duration since diagnosis was four
      years. Participants with CHD/stroke were older with greater prevalence of
      smoking, overweight, hypertension and diabetes (p < 0.01). In patients with CHD,
      stroke and CHD/stroke, respectively, use (%) of antiplatelets was 11.6, 3.8 and
      9.3, beta-blockers 11.9, 7.0 and 10.4, angiotensin-converting enzyme inhibitors
      or angiotensin receptor blockers 6.4, 1.9 and 5.3 and statins 4.8, 0.6 and 3.5.
      In CHD/stroke patients any one of these drugs was used in 18.1%, any two in 7.2%,
      any three in 2.8% and none in 81.5%. Details of drug dose were not available. Use
      of drugs was significantly lower in rural low education and low wealth index
      participants (all p < 0.01). Low wealth index participants had the lowest use of
      these therapies with no attenuation after multiple adjustments. CONCLUSION: The
      use of secondary preventive drug therapies in patients with known CHD or stroke
      in South Asia is low with over 80% receiving none of the effective drug
      treatments. Low household wealth is the most important determinant.

PMID- 24942226
TI  - Treatment with p33 curtails morbidity and mortality in a histone-induced murine
      shock model.
AB  - Collateral damage caused by extracellular histones has an immediate impact on
      morbidity and mortality in many disease models. A significant increase in the
      levels of extracellular histones is seen in critically ill patients with trauma
      and sepsis. We showed that histones are released from necrotic cells in patients
      with invasive skin infections. Under in vitro conditions, endogenous p33, an
      endothelial surface protein also known as the gC1q receptor, interacts with
      histones released from damaged endothelial cells. Functional analyses have
      revealed that recombinantly expressed p33 completely neutralizes the harmful
      features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells
      and platelet aggregation. We also noted that mice treated with a sublethal dose
      of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue
      damage already 10 min after inoculation. These complications were fully
      counteracted when p33 was administered together with the histones. Moreover,
      application of p33 significantly improved survival in mice receiving an otherwise
      lethal dose of histones. Together, our data suggest that treatment with p33 is a
      promising therapeutic approach in severe infectious diseases.

PMID- 24942225
TI  - Identification alone versus intraoperative neuromonitoring of the recurrent
      laryngeal nerve during thyroid surgery: experience of 2034 consecutive patients.
AB  - BACKGROUND: The aim of this study was to evaluate the ability of intraoperative
      neuromonitoring in reducing the postoperative recurrent laryngeal nerve palsy
      rate by a comparison between patients submitted to thyroidectomy with
      intraoperative neuromonitoring and with routine identification alone. METHODS:
      Between June 2007 and December 2012, 2034 consecutive patients underwent
      thyroidectomy by a single surgical team. We compared patients who have had
      neuromonitoring and patients who have undergone surgery with nerve visualization
      alone. Patients in which neuromonitoring was not utilized (Group A) were 993,
      patients in which was utilized (group B) were 1041. RESULTS: In group A 28
      recurrent laryngeal nerve injuries were observed (2.82%), 21 (2.11%) transient
      and 7 (0.7%) permanent. In group B 23 recurrent laryngeal nerve injuries were
      observed (2.21%), in 17 cases (1.63%) transient and in 6 (0.58%) permanent.
      Differences were not statistically significative. CONCLUSIONS: Visual nerve
      identification remains the gold standard of recurrent laryngeal nerve management
      in thyroid surgery. Neuromonitoring helps to identify the nerve, in particular in
      difficult cases, but it did not decrease nerve injuries compared with
      visualization alone. Future studies are warranted to evaluate the benefit of
      intraoperative neuromonitoring in thyroidectomy, especially in conditions in
      which the recurrent nerve is at high risk of injury.

PMID- 24942227
TI  - Survey of the Japanese coast reveals abundant placozoan populations in the
      Northern Pacific Ocean.
AB  - Placozoans are the simplest extant free-living animals consisting of only five
      cell types and lacking neurons and muscle cells. Their phylogenetic position
      implies they are important for uncovering the origins of metazoans. Although
      recent studies show multiple groups within the phylum, most placozoan research
      has been performed on laboratory-cultured clones deriving from a single specimen.
      Reports of placozoan discovery are concentrated in the tropic and subtropic seas,
      especially in the Mediterranean and the Caribbean. Here, I report the unexpected
      abundance of placozoans from the Japanese coast. They were found from all six
      studied sites, even during winter for two sites, suggesting that they are more
      tolerant to low temperatures than previously regarded. These results suggest an
      unknown abundance of placozoans in the Northern Pacific Ocean and further studies
      on these populations may be essential in solving important biological problems of
      the phylum. 

PMID- 24942228
TI  - Approach toward an efficient inoculum preparation stage for suspension BHK-21
      cell culture.
AB  - Mammalian cells are the most frequently used hosts for biopharmaceutical proteins
      manufacturing. Inoculum quality is a key element for establishing an efficient
      bioconversion process. The main objective in inoculation expansion process is to
      generate large volume of viable cells in the shortest time. The aim of this paper
      was to optimize the inoculum preparation stage of baby hamster kidney (BHK)-21
      cells for suspension cultures in benchtop bioreactors, by means of a combination
      of static and agitated culture systems. Critical parameters for static (liquid
      column height: 5, 10, 15 mm) and agitated (working volume: 35, 50, 65 mL,
      inoculum volume percentage: 10, 30 % and agitation speed: 25, 60 rpm) cultures
      were study in T-flask and spinner flask, respectively. The optimal liquid column
      height was 5 mm for static culture. The maximum viable cell concentration in
      spinner flask cultures was reached with 50 mL working volume and the inoculum
      volume percentage was not significant in the range under study (10-30 %) at 25
      rpm agitation. Agitation speed at 60 rpm did not change the main kinetic
      parameters with respect to those observed for 25 rpm. These results allowed for a
      schedule to produce more than 4 * 10(9) BHK-21 cells from 4 * 10(6) cells in 13
      day with 1,051 mL culture medium. 

PMID- 24942230
TI  - Can green solvents be alternatives for thermal stabilization of collagen?
AB  - "Go Green" campaign is gaining light for various industrial applications where
      water consumption needs to be reduced. To resolve this, industries have adopted
      usage of green, organic solvents, as an alternative to water. For leather making,
      tanning industry consumes gallons of water. Therefore, for adopting green
      solvents in leather making, it is necessary to evaluate its influence on type I
      collagen, the major protein present in the skin matrix. The thermal stability of
      collagen from rat tail tendon fiber (RTT) treated with seven green solvents
      namely, ethanol, ethyl lactate, ethyl acetate, propylene carbonate, propylene
      glycol, polyethylene glycol-200 and heptane was determined using differential
      scanning calorimetry (DSC). Crosslinking efficiency of basic chromium sulfate and
      wattle on RTT in green solvents was determined. DSC thermograms show increase in
      thermal stability of RTT collagen against heat with green solvents (>78 degrees
      C) compared to water (63 degrees C). In the presence of crosslinkers, RTT
      demonstrated thermal stability >100 degrees C in some green solvents, resulting
      in increased intermolecular forces between collagen, solvent and crosslinkers.
      The significant improvement in thermal stability of collagen potentiates the
      capability of green solvents as an alternative for water. 

PMID- 24942229
TI  - The association between vaginal parity and hiatal dimensions: a retrospective
      observational study in a tertiary urogynaecological centre.
AB  - OBJECTIVE: Vaginal childbirth has a substantial effect on pelvic organ supports,
      which may be mediated by levator ani (LA) avulsion or hiatal overdistension.
      Although the impact of a first vaginal delivery on the hiatus has been
      investigated, little is known about the effect of subsequent births. This study
      was designed to evaluate the association between vaginal parity and hiatal
      dimension. DESIGN: Retrospective observational study. SETTING: A tertiary
      urogynaecological unit in Australia. POPULATION: A total of 780 archived data
      sets of women seen for symptoms of lower urinary tract and pelvic floor
      dysfunction. METHODS: Standardised in-house interview and assessment using the
      International Continence Society (ICS) pelvic organ prolapse quantification (POP
      Q), and four-dimensional translabial ultrasound. Offline analysis for hiatal
      dimensions was undertaken blinded to history and clinical examination. MAIN
      OUTCOME MEASURES: Hiatal area on maximum Valsalva. RESULTS: Of 780 women, 64 were
      excluded because of missing ultrasound volumes, leaving 716 for analysis: 96% (n
      = 686) were parous, with a median parity of three (interquartile range, IQR 2-3),
      and 91.2% (n = 653) were vaginally parous. Levator avulsion was found in 21% (n =
      148). The mean hiatal area on Valsalva was 29 cm(2) (SD 9.4 cm(2) ). On one-way
      anova, vaginal parity was significantly associated with hiatal area (P < 0.001).
      Most of the effect seems to occur with the first delivery. Subsequent deliveries
      do not seem to have any significant effect on hiatal dimensions. This remained
      true after controlling for potential confounding factors using multivariate
      regression analysis (P = 0.0123). CONCLUSIONS: Vaginal parity was strongly
      associated with hiatal area on Valsalva. Most of this effect seems to be
      associated with the first vaginal delivery.

PMID- 24942231
TI  - Association of gingivitis with child oral health-related quality of life.
AB  - BACKGROUND: Child oral health-related quality of life (COHRQoL) has been
      increasingly assessed. However, the full relationship between gingivitis and
      COHRQoL has been assessed by only a small number of studies. This study aims to
      assess the association between gingival bleeding and how a child perceives its
      OHRQoL. METHODS: This cross-sectional study used multistage random sampling to
      enroll 1,134 12-year-old schoolchildren from Santa Maria, a southern city in
      Brazil. Participants were examined for gingival bleeding according to the
      community periodontal index criteria, a full-mouth clinical examination of six
      sites per tooth. COHRQoL was assessed by the Brazilian version of the Child
      Perceptions Questionnaire for 11- to 14-Year-Old Children (CPQ11-14), and data on
      socioeconomic status were collected. Multilevel Poisson regression models fitted
      the association of gingivitis with overall and domain-specific CPQ11-14 scores.
      RESULTS: In general, children with bleeding in >=15% of sites had higher total
      CPQ11-14 scores and domain-specific scores than their counterparts. This
      association persisted after adjustment for other potential confounders. The
      presence and extent of gingival bleeding was associated mainly with emotional
      limitation domains of the CPQ11-14; those with extended levels of gingivitis had
      a 1.20 times higher mean score than those with low-level/no gingival bleeding
      (rate ratio = 1.20; 95% confidence interval = 1.10 to 1.31). CONCLUSION: The
      present results indicate that the presence of extensive levels of gingivitis
      might be negatively associated with how children perceive their oral health and
      their daily life.

PMID- 24942232
TI  - 3D-printing of lightweight cellular composites.
AB  - A new epoxy-based ink is reported, which enables 3D printing of lightweight
      cellular composites with controlled alignment of multiscale, high-aspectratio
      fiber reinforcement to create hierarchical structures inspired by balsa wood.
      Young's modulus values up to 10 times higher than existing commercially available
      3D-printed polymers are attainable, while comparable strength values are
      maintained. 

PMID- 24942235
TI  - Expression status of let-7a and miR-335 among breast tumors in patients with and
      without germ-line BRCA mutations.
AB  - The genetic factors of cancer predisposition remain elusive in the majority of
      familial and/or early-onset cases of breast cancer (BC). This type of BC is
      promoted by germ-line mutations that inactivate BRCA1 or BRCA2. On the other
      hand, recent studies have indicated that alterations in the levels of miRNA
      expression are linked to this disease. Although BRCA1 and BRCA2 gene mutations
      have been reported to commonly lead to alterations in genes that encode cancer
      related proteins, little is known regarding the putative impact of these
      mutations on noncoding miRNAs. In the present study, we aimed to determine
      whether miRNA dysregulation is involved in the pathogenesis of BRCA-mutated BC.
      An expression analysis of 14 human miRNAs previously shown to be related to BC
      diagnosis, prognosis, and drug resistance was conducted using tissues from 60
      familial and/or early-onset patients whose peripheral blood samples had been
      screened for BRCA1 and BRCA2 mutations through sequence analysis. Let-7a and miR
      335 expression levels were significantly downregulated in the tumors of patients
      with a BRCA mutation compared with those of patients without a BRCA mutation (P =
      0.04 and P = 0.02, respectively). Our results defined the associations between
      the expression status of let-7a and miR-335 and BRCA mutations. The expression
      analysis of these miRNAs might be used as biomarkers of the BRCA mutation status
      of early-onset and/or familial BC. 

PMID- 24942236
TI  - Nicotine impact on melanogenesis and antioxidant defense system in HEMn-DP
      melanocytes.
AB  - Nicotine is a compound of tobacco plants and is responsible for addictive
      properties of tobacco which is used by about one billion of smokers all over the
      world. Recently, nicotine has drawn even more attention due to its presumed
      neuroprotective and antioxidant features as far as common use in various forms of
      smoking cessation therapies. It is suggested that nicotine may be accumulated in
      human tissues containing melanin. This may in turn influence biochemical
      processes in human cells producing melanin. The aim of this study was to examine
      the impact of nicotine on melanogenesis and antioxidant defense system in
      cultured normal human melanocytes (HEMn-DP). Nicotine induced concentration
      dependent loss in melanocytes viability. The value of EC50 was determined to be
      2.52 mM. Nicotine modulated melanin biosynthesis in normal human melanocytes.
      Significant changes in hydrogen peroxide content and cellular antioxidant
      enzymes: SOD, CAT, and GPx activities were stated in melanocytes exposed to
      nicotine, which indicates alterations of antioxidant defense system. The results
      obtained in vitro may explain a potential influence of nicotine on biochemical
      processes in melanocytes in vivo during long-term exposition to nicotine. 

PMID- 24942237
TI  - Neonatal blue light phototherapy increases cafe-au-lait macules in preschool
      children.
AB  - Neonatal blue light phototherapy (NBLP) is an effective treatment for
      hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting
      studies have been published. To assess the role of NBLP according to the
      incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year
      old children were included. The case group consisted of 52 NBLP-exposed children,
      while the control group (n = 52) never had NBLP and was matched regarding age,
      gender, gestational age and skin phototype. Six dizygotic twins were included
      with one twin having received NBLP, respectively. The following parameters were
      recorded: nevi count, presence of freckles, cafe-au-lait macules, skin phototype
      and previous history of sun exposure. There was no significant association
      between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5
      in controls). No significant difference was also found in the dizygotic twin
      pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without
      NBLP). However, a significantly higher prevalence of cafe-au-lait macules was
      found in children with NBLP (mean count 0.5) than in children without NBLP (mean
      count 0.2; p = 0.001). Significant predictors for the number of melanocytic nevi
      included skin phototype, sun exposure and vacations in the South. CONCLUSION: In
      this study, NBLP had no significant influence on the development of melanocytic
      nevi, but on cafe-au-lait macules which was a new finding. Differences with
      comparable studies regarding age, differentiation between nevi and other
      pigmented lesions as well as dose and type of NBLP need to be taken into account
      for further investigations.

PMID- 24942238
TI  - Validation of a Paediatric Early Warning Score: first results and implications of
      usage.
AB  - Timely recognition of deterioration of hospitalised children is important to
      improve mortality. We developed a modified Paediatric Early Warning Score (PEWS)
      and studied the effects by performing three different cohort studies using
      different end points. Taking unplanned Paediatric Intensive Care Unit admission
      as end point and only using data until 2 h prior to end point, we found a
      sensitivity of 0.67 and specificity of 0.88 to timely recognise patients. This
      proves that earlier identification is possible without a loss of sensitivity
      compared to other PEWS systems. When determining the corresponding clinical
      condition in patients with an elevated PEWS dichotomously as 'sick' or 'well',
      this resulted in a total of 27 % false-positive scores. This can cause
      motivational problems for caregivers to use the system but is a consequence of
      PEWS design to minimise false-negative rates because of high mortality associated
      with paediatric resuscitation. Using the need for emergency medical interventions
      as end point, sensitivity of PEWS is high and it seems, therefore, that it is
      also fit to alert health-care professionals that urgent interventions may be
      needed. CONCLUSION: These data show the effectiveness of a modified PEWS in
      identifying critically ill patients in an early phase making early interventions
      possible and hopefully reduce mortality.

PMID- 24942239
TI  - Oral sucrose administration to reduce pain response during immunization in 16-19
      month infants: a randomized, placebo-controlled trial.
AB  - Although the analgesic effect of sucrose on newborns is well established, little
      is known about whether these solutions are effective in reducing procedural pain
      in infants beyond the newborn period. The purpose of this study was to determine
      the effect of sucrose solution given orally on infant crying times and measure
      the distress in a 16-19-month age group. A total of 537 healthy, 16-19-month-old
      infants attending for their immunizations with intramuscular diphtheria, tetanus,
      and acellular pertussis (DTaP)/Haemophilus influenza type b/IPV (along with oral
      polio vaccination (OPV)), intramuscular pneumococcus and intramuscular hepatitis
      A were randomized to receive 2 mL of a 75 % sucrose solution, a 25 % sucrose
      solution or sterile water 2 min before injections. Infants receiving a 75 %
      sucrose solution had significantly reduced total crying times and Children's
      Hospital of Eastern Ontario Pain Scale scores (CHEOPS) compared with infants in
      the control and 25 % sucrose solution groups (p < 0.001). CONCLUSION: Sucrose
      solution reduces infant distress and is safe and clinically useful even for 16-19
      month-old infants.

PMID- 24942240
TI  - Urinary brain-derived neurotrophic factor as a biomarker of executive
      functioning.
AB  - BACKGROUND/AIMS: Neurotrophins such as brain-derived neurotrophic factor (BDNF)
      are vital for neuronal survival and adaptive plasticity. With high BDNF gene
      expression in the prefrontal cortex, BDNF is a potential regulatory factor for
      building and maintaining cognitive reserves. Recent studies suggest that
      individual differences in executive functioning, a broad cognitive domain reliant
      upon frontal lobe structure and function, are governed in part by variance in
      BDNF polymorphisms. However, as neurogenetic data are not necessarily indicative
      of in vivo neurochemistry, this study examines the relationship between executive
      functioning and the neurotransmitter by measuring peripheral BDNF levels.
      METHODS: Fifty-two healthy young adults completed a battery of standardized
      executive function tests. BDNF levels, adjusted for creatinine, were quantified
      with enzyme-linked immunosorbent assay of urine samples taken at the time of
      testing. RESULTS: BDNF concentration was positively associated with cognitive
      flexibility but had no relationship with working memory, abstract
      reasoning/planning, self-monitoring/response inhibition, or fluency. CONCLUSIONS:
      These results individuate cognitive flexibility as the specific facet of
      executive functioning associated with in vivo BDNF levels. This study also
      validates urinary BDNF as a peripheral biomarker of cognition in healthy adults.

PMID- 24942241
TI  - Unequal access, low vaccination coverage, growth retardation rates among
      immigrants children in Italy exacerbated in Roma immigrants.
AB  - AIM: Currently children of immigrants are the fastest growing segment of the
      Italian population under the age of 18. The present study reports the challenges
      to health services access, the vaccination coverage, the health and nutritional
      status of a sample of 1310 children of immigrants attended from February 2004 to
      May 2012 the health center "Medicina Solidale" of the "Policlinico Tor Vergata"
      in the suburban area of the VIII Municipality of Rome. METHODS: The data were
      collected using clinical archives of the health center. We analyzed the socio
      demographic conditions, health problems and nutritional status on admission to
      the health center. The anthropometric evaluation was carried out according to
      international standards of child growth WHO 2006 and the statistical analysis was
      performed using SPSS version 19, and including risk estimation, Mantel Haentzel
      statistics and t-test. RESULTS: Sixty-six percent of the children were born in
      Italy, 62% had never had regular health care and 3.4% of children older than six
      months had never received any of the immunizations. It has been estimated that
      being Roma the risk of not been vaccinated is equal to OR=5.4 (IC95%: 2.8-10.1).
      Seventy-seven percent of unvaccinated children had at least one illiterate
      parent. This condition was strongly associated with non-immunization (OR=15:36
      [IC95%: 6.4-36.4]). Growth retardation was common in Roma children as compared to
      other ethnicities. CONCLUSION: Significant public health efforts are needed to
      improve access to health services for immigrant populations and to solve relevant
      inequalities.

PMID- 24942242
TI  - Gene duplication followed by exon structure divergence substitutes for
      alternative splicing in zebrafish.
AB  - In this study we report novel findings regarding the evolutionary relationship
      between gene duplication and alternative splicing, two processes that increase
      proteomic diversity. By studying teleost fish, we find that gene duplication
      followed by exon structure divergence between paralogs, but not gene duplication
      alone, leads to a significant reduction in alternative splicing, as measured by
      both the proportion of genes that undergo alternative splicing as well as mean
      number of transcripts per gene. Additionally, we show that this effect is
      independent of gene family size and gene function. Furthermore, we provide
      evidence that the reduction in alternative splicing may be due to the
      partitioning of ancestral splice forms among the duplicate genes - a form of
      subfunctionalization. Taken together these results indicate that exon structure
      evolution subsequent to gene duplication may be a common substitute for
      alternative splicing. 

PMID- 24942243
TI  - An MLPA-based approach for high-resolution genotyping of disease-related multi
      allelic CNVs.
AB  - Copy number variation has recently been recognized as an important type of
      genetic variation that modifies human phenotypes. Copy number variants (CNVs) are
      being increasingly associated with various human phenotypes and diseases.
      However, the lack of an appropriate method that allows fast, inexpensive and,
      most importantly, accurate CNVs genotyping significantly hampers CNV analysis.
      This limitation especially affects the analysis of multi-allelic CNVs that
      frequently modify various phenotypes. Recently, we developed a multiplex ligation
      dependent probe amplification (MLPA)-based strategy for multiplex copy number
      genotyping and the validation of candidate CNV-miRNAs. Here we present the
      adaptation and optimization of this recently developed method for high-resolution
      genotyping of individual disease-related multi-allelic CNVs. We developed
      appropriate assays for three well-known and extensively studied CNVs: CNV-CCL3L1,
      CNV-DEFB, and CNV-UGT2B17, which have been associated with various human
      phenotypes including inflammation-related and infectious diseases. With the use
      of these assays we identified several general factors that allow to increase the
      resolution of the copy number genotyping. Performed experiments confirmed the
      high reproducibility and accuracy of the obtained genotyping results. The
      reliability of the results and relatively low per-genotype cost makes this
      strategy an attractive method for large-scale experiments such as genotype
      phenotype association studies. 

PMID- 24942244
TI  - Scale-down characterization of post-centrifuge flocculation processes for high
      throughput process development.
AB  - The authors present a novel ultra scale-down (USD) methodology for the
      characterization of flocculation processes. This USD method, consisting of a
      multiwell, magnetically agitated system that can be fitted on the deck of a
      liquid handling robot, mimicked the flocculation performance of a
      nongeometrically similar pilot-scale vessel representing greater than three
      orders of magnitude scale-up. Mixing scales (i.e. macromixing, mesomixing or
      micromixing) modulated the flocs' size and determined the success of some of the
      scale-up correlations reviewed in the literature. 

PMID- 24942246
TI  - Subtlex-pl: subtitle-based word frequency estimates for Polish.
AB  - We present SUBTLEX-PL, Polish word frequencies based on movie subtitles. In two
      lexical decision experiments, we compare the new measures with frequency
      estimates derived from another Polish text corpus that includes predominantly
      written materials. We show that the frequencies derived from the two corpora
      perform best in predicting human performance in a lexical decision task if used
      in a complementary way. Our results suggest that the two corpora may have unequal
      potential for explaining human performance for words in different frequency
      ranges and that corpora based on written materials severely overestimate
      frequencies for formal words. We discuss some of the implications of these
      findings for future studies comparing different frequency estimates. In addition
      to frequencies for word forms, SUBTLEX-PL includes measures of contextual
      diversity, part-of-speech-specific word frequencies, frequencies of associated
      lemmas, and word bigrams, providing researchers with necessary tools for
      conducting psycholinguistic research in Polish. The database is freely available
      for research purposes and may be downloaded from the authors' university Web site
      at http://crr.ugent.be/subtlex-pl . 

PMID- 24942245
TI  - Thimerosal induces apoptotic and fibrotic changes to kidney epithelial cells in
      vitro.
AB  - Thimerosal is an ethyl mercury-containing compound used mainly in vaccines as a
      bactericide. Although the kidney is a key target for mercury toxicity, thimerosal
      nephrotoxicity has not received the same attention as other mercury species. The
      aim of this study was to determine the potential cytotoxic mechanisms of
      thimerosal on human kidney cells. Human kidney proximal tubular epithelial (HK2)
      cells were exposed for 24 h to thimerosal (0-2 uM), and assessed for cell
      viability, apoptosis, and cell proliferation; expression of proteins Bax, nuclear
      factor-kappaB subunits, and transforming growth factor-beta1 (TGFbeta1);
      mitochondrial health (JC-1, MitoTracker Red CMXRos); and fibronectin levels
      (enzyme-linked immunosorbent assay). Thimerosal diminished HK2 cell viability and
      mitosis, promoted apoptosis, impaired the mitochondrial permeability transition,
      enhanced Bax and TGFbeta1 expression, and augmented fibronectin secretion. This
      is the first report about kidney cell death and pro-fibrotic mechanisms promoted
      by thimerosal. Collectively, these in vitro results demonstrate that (1)
      thimerosal induces kidney epithelial cell apoptosis via upregulating Bax and the
      mitochondrial apoptotic pathway, and (2) thimerosal is a potential pro-fibrotic
      agent in human kidney cells. We suggest that new evidence on toxicity as well as
      continuous surveillance in terms of fibrogenesis is required concerning
      thimerosal use.

PMID- 24942247
TI  - Manipulability agreement as a predictor of action initiation latency.
AB  - In the domain of cognition, an increasing number of researchers are interested in
      the role of objects' motor affordances in cognitive processing. However, outside
      of the existing norms on the objects' levels of manipulability (e.g., Magnie,
      Besson, Poncet, & Dolisi, Journal of Clinical and Experimental Neuropsychology,
      25:521-560,2003), relatively few norms exist that would allow researchers to have
      good control over objects' motor dimensions. In the present study, we have
      provided norms on the extent to which participants agreed about the movements
      typically performed for using specific objects--what we will call manipulability
      agreement. We showed that manipulability agreement was a good predictor of the
      times needed to initiate the action associated with the object. This study
      provides ratings on a new dimension of objects' motor affordances that could be
      useful to researchers in the domain of visual cognition.

PMID- 24942248
TI  - Using the speeded word fragment completion task to examine semantic priming.
AB  - The present research investigates semantic priming with an adapted version of the
      word fragment completion task. In this task, which we refer to as the speeded
      word fragment completion task, participants need to complete words such as
      lett_ce (lettuce), from which one letter was omitted, as quickly as possible.
      This paradigm has some interesting qualities in comparison with the traditionally
      used lexical decision task. That is, it requires no pseudowords, it is more
      engaging for participants, and most importantly, it allows for a more fine
      grained investigation of semantic activation. In two studies, we found that words
      were completed faster when the preceding trial comprised a semantically related
      fragment such as tom_to (tomato) than when it comprised an unrelated fragment
      such as guit_r (guitar). A third experiment involved a lexical decision task, to
      compare both paradigms. The results showed that the magnitude of the priming
      effect was similar, but item-level priming effects were inconsistent over tasks.
      Crucially, the speeded word fragment completion task obtained strong priming
      effects for highly frequent, central words, such as work, money, and warm,
      whereas the lexical decision task did not. In a final experiment featuring only
      short, highly frequent words, the lexical decision task failed to find a priming
      effect, whereas the fragment completion task did obtain a robust effect. Taken
      together, these results suggest that the speeded word fragment completion task
      may prove a viable alternative for examining semantic priming. 

PMID- 24942249
TI  - New frontiers in the rubber hand experiment: when a robotic hand becomes one's
      own.
AB  - The rubber hand illusion is an experimental paradigm in which participants
      consider a fake hand to be part of their body. This paradigm has been used in
      many domains of psychology (i.e., research on pain, body ownership, agency) and
      is of clinical importance. The classic rubber hand paradigm nevertheless suffers
      from limitations, such as the absence of active motion or the reliance on
      approximate measurements, which makes strict experimental conditions difficult to
      obtain. Here, we report on the development of a novel technology-a robotic, user-
      and computer-controllable hand-that addresses many of the limitations associated
      with the classic rubber hand paradigm. Because participants can actively control
      the robotic hand, the device affords higher realism and authenticity. Our robotic
      hand has a comparatively low cost and opens up novel and innovative methods. In
      order to validate the robotic hand, we have carried out three experiments. The
      first two studies were based on previous research using the rubber hand, while
      the third was specific to the robotic hand. We measured both sense of agency and
      ownership. Overall, results show that participants experienced a "robotic hand
      illusion" in the baseline conditions. Furthermore, we also replicated previous
      results about agency and ownership. 

PMID- 24942250
TI  - Climate and the landscape of fear in an African savanna.
AB  - Herbivores frequently have to make trade-offs between two basic needs: the need
      to acquire forage and the need to avoid predation. One manifestation of this
      trade-off is the 'landscape of fear' phenomenon - wherein herbivores avoid areas
      of high perceived predation risk even if forage is abundant or of high quality in
      those areas. Although this phenomenon is well established among invertebrates,
      its applicability to terrestrial large herbivores remains debated, in part
      because experimental evidence is scarce. This study was designed to (i)
      experimentally test the effects of tree density - a key landscape feature
      associated with predation risk for African ungulates - on herbivore habitat use
      and (ii) establish whether habitat use patterns could be explained by trade-offs
      between foraging opportunities and predation risk avoidance. In a Kenyan savanna
      system, replicate plots dominated by the tree Acacia drepanolobium were cleared,
      thinned or left intact. Ungulate responses were measured over four years, which
      included years of moderate rainfall as well as a severe drought. Under average
      rainfall conditions, most herbivores (primarily plains zebra, Grant's gazelle and
      hartebeest) favoured sites with fewer trees and higher visibility - regardless of
      grass production - while elephants (too large to be vulnerable to predation)
      favoured sites with many trees. During the drought, however, herbivores favoured
      sites that had high grass biomass, but not high visibility. Thus, during the
      drought, herbivores sought areas where food was more abundant, despite probable
      higher risk of predation. These results illustrate that the 'landscape of fear',
      and the associated interactions between top-down and bottom-up effects, is not
      static, but rather shifts markedly under different conditions. Climate thus has
      the potential to alter the strength and spatial dynamics of behaviourally
      mediated cascades in large herbivore systems. 

PMID- 24942251
TI  - Exploring nocturia: gender, age, and causes.
AB  - PURPOSE: This study aims to clarify differences in parameters based on frequency
      volume chart (FVC) and on daytime and nighttime urine according to the nocturia
      frequency, age, and gender. MATERIALS AND METHODS: This observational study was
      executed between 2011 and 2013. Participants (>18 years, <=65 years) with or
      without nocturia (controls) were included and completed a 72 hr FVC; osmolality
      and sodium excretion were analyzed on daytime and nighttime urine. RESULTS: (1)
      Nocturia severity: Compared to controls (N = 38), those with >=2 nocturia
      episodes (N = 29) have higher nocturnal voided volume (NVV) (P < 0.001) based on
      increased sodium excretion (P = 0.003) and lower functional bladder capacity (P <
      0.001). Those with one nocturia episode (N = 21) present with lower bladder
      capacity (P = 0.005). (2) Gender: women with 1 and >=2 episodes have lower
      bladder capacity than controls (P = 0.047 and P < 0.001, respectively). Men with
      >=2 episodes present with increased NVV (P = 0.001) and decreased bladder
      capacity (P = 0.049). (3) Age: Younger participants (<44 years) with >=2 nocturia
      episodes present with lower functional bladder capacity than controls (P <
      0.001). Older participants (45-65 years) present with both increasing NVV and
      decreasing bladder capacity with increasing nocturia frequency (P < 0.001);
      sodium excretion is higher in those with >=2 episodes (P = 0.029). (4) Causes:
      the percentage of isolated NP decreases (P = 0.005), whereas the combination of
      both causes increases with increase in number of nocturia episodes (P = 0.020).
      CONCLUSIONS: The mismatch between functional bladder capacity and NVV with
      increasing nocturia frequency demands a comprehensive diagnostic approach to
      subtype the patient, which involves anamnesis, FVC, and analysis of daytime and
      nighttime urine.

PMID- 24942252
TI  - Leaf out times of temperate woody plants are related to phylogeny, deciduousness,
      growth habit and wood anatomy.
AB  - Leaf out phenology affects a wide variety of ecosystem processes and ecological
      interactions and will take on added significance as leaf out times increasingly
      shift in response to warming temperatures associated with climate change. There
      is, however, relatively little information available on the factors affecting
      species differences in leaf out phenology. An international team of researchers
      from eight Northern Hemisphere temperate botanical gardens recorded leaf out
      dates of c. 1600 woody species in 2011 and 2012. Leaf out dates in woody species
      differed by as much as 3 months at a single site and exhibited strong
      phylogenetic and anatomical relationships. On average, angiosperms leafed out
      earlier than gymnosperms, deciduous species earlier than evergreen species,
      shrubs earlier than trees, diffuse and semi-ring porous species earlier than ring
      porous species, and species with smaller diameter xylem vessels earlier than
      species with larger diameter vessels. The order of species leaf out was generally
      consistent between years and among sites. As species distribution and abundance
      shift due to climate change, interspecific differences in leaf out phenology may
      affect ecosystem processes such as carbon, water, and nutrient cycling. Our open
      access leaf out data provide a critical framework for monitoring and modelling
      such changes going forward. 

PMID- 24942254
TI  - Should sex chromosomes be excluded from use in QF-PCR in prenatal samples with a
      molecular referral?

PMID- 24942253
TI  - Towards highly accelerated Cartesian time-resolved 3D flow cardiovascular
      magnetic resonance in the clinical setting.
AB  - BACKGROUND: The clinical applicability of time-resolved 3D flow cardiovascular
      magnetic resonance (CMR) remains compromised by the long scan times associated
      with phase-contrast imaging. The present work demonstrates the applicability of 8
      fold acceleration of Cartesian time-resolved 3D flow CMR in 10 volunteers and in
      9 patients with different congenital heart diseases (CHD). It is demonstrated
      that accelerated 3D flow CMR data acquisition and image reconstruction using k-t
      PCA (principal component analysis) can be implemented into clinical workflow and
      results are sufficiently accurate relative to conventional 2D flow CMR to permit
      for comprehensive flow quantification in CHD patients. METHODS: The fidelity of k
      t PCA was first investigated on retrospectively undersampled data for different
      acceleration factors and compared to k-t SENSE and fully sampled reference data.
      Subsequently, k-t PCA with 8-fold nominal undersampling was applied on 10 healthy
      volunteers and 9 CHD patients on a clinical 1.5 T MR scanner. Quantitative flow
      validation was performed in vessels of interest on the 3D flow datasets and
      compared to 2D through-plane flow acquisitions. Particle trace analysis was used
      to qualitatively visualise flow patterns in patients. RESULTS: Accelerated time
      resolved 3D flow data were successfully acquired in all subjects with 8-fold
      nominal scan acceleration. Nominal scan times excluding navigator efficiency were
      on the order of 6 min and 7 min in patients and volunteers. Mean differences in
      stroke volume in selected vessels of interest were 2.5 +/- 8.4 ml and 1.63 +/-
      4.8 ml in volunteers and patients, respectively. Qualitative flow pattern
      analysis in the time-resolved 3D dataset revealed valuable insights into
      hemodynamics including circular and helical patterns as well as flow
      distributions and origin in the Fontan circulation. CONCLUSION: Highly
      accelerated time-resolved 3D flow using k-t PCA is readily applicable in clinical
      routine protocols of CHD patients. Nominal scan times of 6 min are well tolerated
      and allow for quantitative and qualitative flow assessment in all great vessels.

PMID- 24942255
TI  - Pd-Catalyzed C-H activation/oxidative cyclization of acetanilide with norbornene:
      concise access to functionalized indolines.
AB  - An efficient Pd-catalyzed oxidative cyclization reaction for the synthesis of
      functionalized indolines by direct C-H activation of acetanilide has been
      developed. The norbornylpalladium species formed via direct ortho C-H activation
      of acetanilides is supposed to be a key intermediate in this transformation. 

PMID- 24942256
TI  - Maternal cigarette smoking during pregnancy predicts drug use via externalizing
      behavior in two community-based samples of adolescents.
AB  - BACKGROUND AND AIMS: Prenatal exposure to maternal cigarette smoking (PEMCS) is
      associated with a higher probability of substance use in adolescence. We explore
      if externalizing behavior mediates this relationship, while controlling for a
      number of potential covariates of this mediation process. METHODS: We used data
      obtained in two geographically distinct community samples of adolescents. The
      first (cross-sectional) sample consisted of 996 adolescents (12-18 years of age)
      recruited from the Saguenay Youth Study (SYS) in Canada (47% with PEMCS). The
      second (longitudinal) sample consisted of 1141 adolescents (49% with PEMCS) from
      the Northern Finland Birth Cohort (NFBC1986). In both samples, externalizing
      behavior and substance use were assessed during adolescence. In the NFBC1986
      cohort, externalizing behavior was also assessed in childhood. RESULTS: In both
      populations, PEMCS is associated with a higher likelihood of adolescent drug
      experimentation. In the NFBC1986 cohort, exposed (versus non-exposed) adolescents
      experiment with an extra 1.27 [B = 0.24, 95% confidence intervals (CI) = 0.15,
      0.33 P < 0.001] drugs. In the SYS cohort, a clear protective effect of not being
      exposed is shown: non-exposed (versus exposed) adolescents are 1.5 times [B = 
      0.42, 95% CI = -0.75, -0.09, P = 0.013] less likely to take drugs. These
      associations between PEMCS and drug experimentation remain in the multivariate
      and mediational analyses. CONCLUSIONS: Prenatal exposure to maternal cigarette
      smoking appears to be associated with a higher probability of experimenting with
      drugs during adolescence, both directly and indirectly via externalizing behavior
      and the number of peers reported as using drugs.

PMID- 24942258
TI  - 'Sportmotorische Bestandesaufnahme': criterion- vs. norm-based reference values
      of fitness tests for Swiss first grade children.
AB  - Health is closely linked to physical activity and fitness. It is therefore
      important to monitor fitness in children. Although many reports on physical tests
      have been published, data comparison between studies is an issue. This study
      reports Swiss first grade norm values of fitness tests and compares these with
      criterion reference data. A total of 10,565 boys (7.18 +/- 0.42 years) and 10,204
      girls (7.14 +/- 0.41 years) were tested for standing long jump, plate tapping, 20
      m shuttle run, lateral jump and 20-m sprint. Average values for six-, seven- and
      eight-year-olds were analysed and reference curves for age were constructed. Z
      values were generated for comparisons with criterion references reported in the
      literature. Results were better for all disciplines in seven-year-old first grade
      children compared to six-year-old children (p < 0.01). Eight-year-old children
      did not perform better compared to seven-year-old children in the sprint run (p =
      0.11), standing long jump (p > 0.99) and shuttle run (p = 0.43), whereas they
      were better in all other disciplines compared to their younger peers. The average
      performance of boys was better than girls except for tapping at the age of 8 (p =
      0.06). Differences in performance due to testing protocol and setting must be
      considered when test values from a first grade setting are compared to criterion
      based benchmarks. In a classroom setting, younger children tended to have better
      results and older children tended to have worse outcomes when compared to their
      age group criterion reference values. Norm reference data are valid allowing
      comparison with other data generated by similar test protocols applied in a
      classroom setting.

PMID- 24942257
TI  - Factors associated with mortality among persistently viraemic triple
      antiretroviral-class-experienced patients receiving antiretroviral therapy in the
      HIV Outpatient Study (HOPS).
AB  - BACKGROUND: Identifying factors associated with mortality for HIV-infected
      patients with persistent viraemia despite antiretroviral (ARV) therapy may inform
      diagnostic and treatment strategies. METHODS: We analysed data from viraemic
      triple-ARV-class-experienced HIV Outpatient Study patients seen during 1 January
      1999 to 31 December 2012 who, despite treatment that included ARVs from three
      major drug classes [nucleoside analogue reverse transcriptase inhibitors, non
      nucleoside analogue reverse transcriptase inhibitors and protease inhibitors
      (PIs)], had plasma HIV RNA levels [viral load (VL)] >1000 copies/mL ['triple ARV
      class failure' (TCF)]. The baseline was defined as the date of meeting the TCF
      criteria during 1999-2008. We identified factors associated with mortality using
      Cox regression. RESULTS: Of 597 patients who met the TCF criteria (median follow
      up after baseline 4.9 years), 115 (19.3%) died. Baseline factors associated with
      mortality were age per 10 years [hazard ratio (HR) 1.61, 95% CI 1.28-2.02], risk
      of HIV from use of injection drugs (HR 1.81, 95% CI 1.10-2.98), CD4+ T cell count
      <200 cells/mm(3) (HR 3.68, 95% CI 2.41-5.62), VL >=5.0 log10 copies/mL (HR 2.91,
      95% CI 1.88-4.49) and receiving a first combination ARV therapy regimen that was
      PI-based (HR 2.44, 95% CI 1.47-4.06); receiving a novel ARV agent during follow
      up (HR 0.45, 95% CI 0.22-0.93) was protective. Genotypic resistance testing
      results were available for 274 (45.9%) of the TCF patients, of whom 47 (17.2%)
      died. In this group, factors associated with death were increasing age (HR 1.94,
      95% CI 1.36-2.78, per 10 year increment), risk of HIV from use of injection drugs
      (HR 2.71, 95% CI 1.37-5.39), baseline VL >=5.0 log10 copies/mL (HR 5.35, 95% CI
      2.82-10.1) and receiving PI-based first combination ARV therapy regimen (HR 3.20,
      95% CI 1.25-8.17). No HIV mutations or combinations of mutations were
      significantly associated with survival. CONCLUSIONS: Factors significantly
      associated with mortality risk among TCF patients who received ongoing ARV
      therapy included traditional clinical predictors but not the presence, type or
      number of HIV genetic mutations. The use of novel ARV drugs by these ARV therapy
      experienced patients was associated with an improved survival.

PMID- 24942259
TI  - Identification of tubular injury microRNA biomarkers in urine: comparison of next
      generation sequencing and qPCR-based profiling platforms.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate protein
      levels post-transcriptionally. miRNAs play important regulatory roles in many
      cellular processes and have been implicated in several diseases. Recent studies
      have reported significant levels of miRNAs in a variety of body fluids, raising
      the possibility that miRNAs could serve as useful biomarkers. Next-generation
      sequencing (NGS) is increasingly employed in biomedical investigations. Although
      concordance between this platform and qRT-PCR based assays has been reported in
      high quality specimens, information is lacking on comparisons in biofluids
      especially urine. Here we describe the changes in miRNA expression patterns in a
      rodent model of renal tubular injury (gentamicin). Our aim is to compare RNA
      sequencing and qPCR based miRNA profiling in urine specimen from control and rats
      with confirmed tubular injury. RESULTS: Our preliminary examination of the
      concordance between miRNA-seq and qRT-PCR in urine specimen suggests minimal
      agreement between platforms probably due to the differences in sensitivity. Our
      results suggest that although miRNA-seq has superior specificity, it may not
      detect low abundant miRNAs in urine samples. Specifically, miRNA-seq did not
      detect some sequences which were identified by qRT-PCR. On the other hand, the
      qRT-PCR analysis was not able to detect the miRNA isoforms, which made up the
      majority of miRNA changes detected by NGS. CONCLUSIONS: To our knowledge, this is
      the first time that miRNA profiling platforms including NGS have been compared in
      urine specimen. miRNAs identified by both platforms, let-7d, miR-203, and miR
      320, may potentially serve as promising novel urinary biomarkers for drug induced
      renal tubular epithelial injury.

PMID- 24942260
TI  - Comprehensive pathological analyses in lung squamous cell carcinoma: single cell
      invasion, nuclear diameter, and tumor budding are independent prognostic factors
      for worse outcomes.
AB  - INTRODUCTION: For lung squamous cell carcinomas, there are no pathological
      findings that have been universally accepted as prognostic factors, with the
      exception of pathological stage. Tumor budding and nuclear grade have been
      recognized as a poor prognostic factor in other carcinomas. In this study, we
      investigated whether pathological findings could determine prognosis in lung
      squamous cell carcinomas. METHODS: All available tumor slides from patients with
      surgically resected, solitary lung squamous cell carcinomas (1999-2009) were
      reviewed (n = 485; stage I/II/III, 281/136/68). Tumors were evaluated for
      differentiation, subtypes (keratinizing, nonkeratinizing, basaloid pattern,
      papillary growth, and clear cell feature), tumor nest size (tumor budding and
      single cell invasion), and nuclear grade (nuclear diameter and mitosis). Overall
      survival (OS) was estimated using the Kaplan-Meier method (stratified by
      pathological stage), and group differences were investigated using the stratified
      log-rank test and the Cox proportional hazards model. RESULTS: OS was
      significantly decreased in patients with versus without single cell invasion (p =
      0.002 for the entire tumor and p = 0.001 for tumor edge), with large versus small
      nuclei (p = 0.011), and with high versus low grade tumor budding (p < 0.001 for
      maximum and p = 0.007 for total). In multivariate analyses, single cell invasion
      (hazard ratio [HR], 1.47-1.49), nuclear diameter (HR, 1.09-1.33), and tumor
      budding (HR, 1.04) were independent prognostic factors of OS. However, histologic
      subtyping including keratinizing, nonkeratinizing, basaloid, and clear cell
      subtypes did not show prognostic significance. CONCLUSIONS: Pathological factors
      can help stratify prognosis in patients with lung squamous cell carcinomas.

PMID- 24942261
TI  - Analysis of CPAF mutants: new functions, new questions (the ins and outs of a
      chlamydial protease).
AB  - The role of the chlamydial protease CPAF, previously described as a secreted
      serine protease processing a wealth of host and chlamydial proteins to promote
      chlamydial intracellular growth, has recently been questioned by studies from the
      groups of Tan and Sutterlin, who demonstrated that the reported proteolysis of
      almost a dozen substrates by CPAF occurred during preparation of cell lysates
      rather than in intact cells. Valdivia et al. have now compared near-isogenic
      pairs of CPAF-deficient and secretion-deficient mutants of Chlamydia trachomatis
      and their wild-type parent. Their report, published in this issue of Pathogens
      and Disease, is a landmark study in the emerging era of Chlamydia genetics. The
      results of Tan and Sutterlin are confirmed with a few additions. While CPAF's
      role in pathogenesis is diminished considerably from these studies, CPAF remains
      an important factor in chlamydial biology as (1) CPAF mutants produce less
      infectious yield than wild type; and (2) CPAF is responsible for proteolytic
      cleavage of vimentin and LAP-1, but only after lysis of the inclusion membrane,
      not upon CPAF secretion to the cytosol. Here, we briefly review the evidence in
      support of CPAF's active secretion from the mid-to-late inclusion and conclude
      that new experimentation to establish whether or not CPAF is actively secreted
      should precede any new investigation of CPAF's cellular activities during mid-to
      late development.

PMID- 24942262
TI  - Twenty years of surveillance in Rett syndrome: what does this tell us?
AB  - BACKGROUND: The clinical characteristics of children diagnosed with Rett syndrome
      are well described. Survival and how these characteristics persist or change in
      adulthood are less well documented. This study aimed to describe overall survival
      and adult health in those with Rett syndrome. METHODS: Using the Kaplan-Meier
      method, we estimated survival of individuals registered with the Australian Rett
      syndrome Database (ARSD) who had been followed for up to 20 years (n = 396). We
      then conducted logistic and linear regression analyses investigating epilepsy,
      musculoskeletal, gastrointestinal, autonomic dysfunction and behaviour of
      individuals aged 18 years and over using cross sectional cohorts from the ARSD (n
      = 150) and the international database InterRett (n = 273). RESULTS: The
      likelihood of survival was 77.6% at 20 years, 71.5% at 25 years and 59.8% at 37
      years. The median age of the combined cross-sectional cohort was 25 years (range
      18 to 54 years), the majority (71%) were living in their parental home and the
      remainder being cared for in group homes or other institutions. Just over half
      walked either independently (18%) or with assistance (43%). The majority (86%)
      had scoliosis with 40% of those having undergone corrective surgery. Almost two
      thirds (64%) of the women were taking anti-epileptic medications at the time of
      data collection. Constipation was highly prevalent (83%) and many experienced
      bloating (53%). Biliary dyskinesia, inflammation or infection of the gallbladder
      was reported for 20 women (5%) and of those 13 had undergone gallbladder surgery.
      Sleep disturbance was relatively common (63%), and adverse mood events and
      anxiety were slightly more prevalent in those aged 26-30 years in comparison to
      the younger and older age groups. Other frequently reported medical conditions
      included urinary tract infections, pneumonia and other respiratory conditions.
      CONCLUSIONS: Survival in Rett syndrome has now been estimated with the most
      accurate follow up to date. During adulthood, continuation of multidisciplinary
      services and programs is necessary to optimise health and wellbeing.

PMID- 24942264
TI  - Esophageal duplication cyst: a rare cause of atrial fibrillation in a young adult
      patient.

PMID- 24942263
TI  - Long term cerebral and vascular complications after irradiation of the neck in
      head and neck cancer patients: a prospective cohort study: study rationale and
      protocol.
AB  - BACKGROUND: Successful treatment options for cancer result in more young long
      term survivors prone for long-term complications. Carotid artery vasculopathy is
      a potential long-term complication after radiotherapy of the neck, resulting in
      cerebrovascular events and probably deficits in cognitive and motor functioning.
      Better insight into the underlying pathofysiology of radiotherapy induced carotid
      artery vasculopathy is needed for prognostic purposes and to develop preventive
      strategies. METHODS/DESIGN: The current study is a prospective cohort study on
      the long-term cerebral and vascular complications after radiotherapy of the neck,
      in 103 patients treated for head and neck cancer, included in our study database
      between 2002 and 2008. Baseline protocol (before radiotherapy) included screening
      for cerebrovascular risk factors and intima media thickness measurement of
      carotid arteries by ultrasonography. Follow-up assessment more than 5 years after
      radiotherapy included screening of cerebrovascular risk factors, cerebrovascular
      events, neurological examination with gait and balance tests, extensive
      neuropsychological examination, self-report questionnaires, ultrasonography of
      the carotid arteries with measurement of intima media thickness and elastography,
      magnetic resonance imaging of the brain and magnetic resonance angiography of the
      carotid arteries. DISCUSSION: The current study adds to the understanding of the
      causes and consequences of long-term cerebral and vascular changes after
      radiotherapy of the neck. These data will be helpful to develop a protocol for
      diagnostic and preventive strategies for long-term neurological complications in
      future head and neck cancer patients with anticipated radiotherapy treatment.

PMID- 24942265
TI  - Tone-deaf ears in moths may limit the acoustic detection of two-tone bats.
AB  - Frequency alternation in the echolocation of insectivorous bats has been
      interpreted in relation to ranging and duty cycle, i.e. advantages for
      echolocation. The shifts in frequency of the calls of these so-called two-tone
      bats, however, may also play its role in the success of their hunting behavior
      for a preferred prey, the tympanate moth. How the auditory receptors (e.g. the A1
      and A2 cells) in the moth's ear detect such frequency shifts is currently
      unknown. Here, we measured the auditory responses of the A1 cell in the noctuid
      Spodoptera frugiperda to the echolocation hunting sequence of Molossus molossus,
      a two-tone bat. We also manipulated the bat calls to control for the frequency
      shifts by lowering the frequency band of the search and approach calls. The
      firing response of the A1 receptor cell significantly decreases with the shift to
      higher frequencies during the search and approach phases of the hunting sequence
      of M. molossus; this could be explained by the receptor's threshold curve. The
      frequency dependence of the decrease in the receptor's response is supported by
      the results attained with the manipulated sequence: search and approach calls
      with the same minimum frequency are detected by the moth at the same threshold
      intensity. The two-tone bat M. molossus shows a call frequency alternation
      behavior that may enable it to overcome moth audition even in the mid-frequency
      range (i.e. 20-50 kHz) where moths hear best.

PMID- 24942266
TI  - 'Getting to zero' in Asia and the Pacific through more strategic use of
      antiretrovirals for HIV prevention.
AB  - Encouraged by experimental trials demonstrating the efficacy of antiretrovirals
      (ARVs) in preventing HIV infection, countries across the Asia-Pacific region have
      committed to the achievement of ambitious targets tantamount to ending AIDS. The
      available data suggest that some countries still can make progress through
      targeted condom promotion and the expansion of harm-reduction interventions, but
      that none may realise its vision of 'zero new HIV infections' without more
      strategic use of ARVs as part of a combination of HIV prevention efforts
      targeting key populations. Low rates of HIV testing among men who have sex with
      men, people who inject drugs, sex workers and other key populations evidence low
      treatment coverage where treatment could have the greatest impact on curbing
      local epidemics. Studies have demonstrated the promise of adding ARV treatment
      and pre-exposure prophylaxis to the existing HIV prevention toolkit, but
      achieving population-level impact will require service-delivery approaches that
      overcome traditional prevention, care and treatment program distinctions.
      Priorities include: (1) innovative strategies to reach, test, treat and retain in
      services the individuals most likely to acquire or transmit HIV; (2) task
      shifting and enhanced partnerships between the public sector and civil society;
      (3) improved 'cascade' data systems to assess and promote service uptake and
      retention; and (4) policy and financing reform to enhance HIV testing and
      treatment access among key populations. 

PMID- 24942267
TI  - Editorial: Reconstructing practice-based educator roles through effective
      practice-education partnerships.

PMID- 24942269
TI  - Commentary on Shin YS, Kim HJ, Moon N-K, Ahn YH and Kim K-O (2012) The effects of
      uncoated paper on skin moisture and transepidermal water loss in bedridden
      patients. Journal of Clinical Nursing 21, 2469-2476.

PMID- 24942268
TI  - Cervical screening and the aftermath of childhood sexual abuse: are clinical
      staff trained to recognise and manage the effect this has on their patients?
AB  - AIMS AND OBJECTIVES: To evaluate the training needs and awareness of childhood
      sexual abuse amongst clinical staff taking cervical screening samples in one
      inner city primary care trust. BACKGROUND: Studies exploring sexual abuse and
      nonparticipation in cervical screening have demonstrated that women can
      experience re-traumatisation if care during examinations is insensitive to their
      particular needs. DESIGN: This was a mixed methods, service evaluation in three
      phases. METHODS: A literature review, a questionnaire to cervical screening staff
      in an inner city primary care trust and a focus group of four staff drawn from
      questionnaire respondents to explore themes raised in the questionnaire data.
      RESULTS: Data analysis of both quantitative and qualitative data showed that
      clinical staff underestimated the frequency of childhood sexual abuse although
      they were aware of the difficulties and reluctance some women experience
      undergoing gynaecological examinations. When women did disclose childhood sexual
      abuse or when staff suspected a history of childhood sexual abuse, staff reported
      feeling unsure of how they should proceed. There was no support or clinical
      supervision, and unmet training needs were identified. CONCLUSIONS: Nurses
      expressed anxiety around the potential of the screening test to cause more harm
      than good and at their inability to provide more help than listening. Staff
      wanted support and further training after completing their cervical screening
      training course to assist in their provision of sensitive care to patients who
      have experienced childhood sexual abuse. RELEVANCE TO CLINICAL PRACTICE: Whilst
      our results cannot be generalised to a wider population, they may be meaningful
      for the community of cervical screening takers. We argue that screening staff
      require further training and professional support (clinical supervision) to
      increase their confidence when providing safe and sensitive practice for
      childhood sexual abuse survivors. If staff feel more confident and competent when
      responding to disclosure of childhood sexual abuse in screening situations, women
      who have experienced childhood sexual abuse might participate in the screening
      programme more readily.

PMID- 24942270
TI  - Establishing key components of yoga interventions for musculoskeletal conditions:
      a Delphi survey.
AB  - BACKGROUND: Evidence suggests yoga is a safe and effective intervention for the
      management of physical and psychosocial symptoms associated with musculoskeletal
      conditions. However, heterogeneity in the components and reporting of clinical
      yoga trials impedes both the generalization of study results and the replication
      of study protocols. The aim of this Delphi survey was to address these issues of
      heterogeneity, by developing a list of recommendations of key components for the
      design and reporting of yoga interventions for musculoskeletal conditions.
      METHODS: Recognised experts involved in the design, conduct, and teaching of yoga
      for musculoskeletal conditions were identified from a systematic review, and
      invited to contribute to the Delphi survey. Forty-one of the 58 experts
      contacted, representing six countries, agreed to participate. A three-round
      Delphi was conducted via electronic surveys. Round 1 presented an open-ended
      question, allowing panellists to individually identify components they considered
      key to the design and reporting of yoga interventions for musculoskeletal
      conditions. Thematic analysis of Round 1 identified items for quantitative rating
      in Round 2; items not reaching consensus were forwarded to Round 3 for re-rating.
      RESULTS: Thirty-six panellists (36/41; 88%) completed the three rounds of the
      Delphi survey. Panellists provided 348 comments to the Round 1 question. These
      comments were reduced to 49 items, grouped under five themes, for rating in
      subsequent rounds. A priori group consensus of >=80% was reached on 28 items
      related to five themes concerning defining the yoga intervention, types of yoga
      practices to include in an intervention, delivery of the yoga protocol, domains
      of outcome measures, and reporting of yoga interventions for musculoskeletal
      conditions. Additionally, a priori consensus of >=50% was reached on five items
      relating to minimum values for intervention parameters. CONCLUSIONS: Expert
      consensus has provided a non-prescriptive reference list for the design and
      reporting of yoga interventions for musculoskeletal conditions. It is anticipated
      future research incorporating the Delphi guidelines will facilitate high quality
      international research in this field, increase homogeneity of intervention
      components and parameters, and enhance the comparison and reproducibility of
      research into the use of yoga for the management of musculoskeletal conditions.

PMID- 24942271
TI  - Validity of noninvasive markers of methotrexate-induced hepatotoxicity: a
      retrospective cohort study.
AB  - BACKGROUND: Methotrexate is a cost-effective systemic treatment for moderate-to
      severe psoriasis, but the perceived risk of associated liver fibrosis prevents
      optimal use. Procollagen III aminoterminal propeptide (PIIINP) is a widely
      adopted noninvasive biomarker of liver fibrosis; however, its clinical utility is
      narrow owing to limited evidence of performance and the need for serial
      measurement. The Enhanced Liver Fibrosis (ELF) assay is a validated biomarker of
      liver fibrosis. OBJECTIVES: To evaluate the diagnostic accuracy of the ELF test
      compared with PIIINP for the diagnosis of liver fibrosis in a cohort of patients
      with psoriasis treated with methotrexate. METHODS: A retrospective cohort study
      comparing the diagnostic accuracy of PIIINP and ELF in detecting liver fibrosis
      in patients treated with methotrexate. Liver biopsy was the reference standard.
      RESULTS: Twenty-seven patients were identified and included in the study. The
      diagnostic accuracies [area under the receiver operating curve (AUROC)] of serial
      PIIINP and serial ELF were 0.589 [95% confidence interval (CI) 0.379-0.800] and
      0.643 (95% CI 0.391-0.895), respectively, for mild fibrosis; and 0.576 (95% CI
      0.237-0.916) and 0.674 (95% CI 0.421-0.927) for at least moderate fibrosis. The
      AUROC values for single PIIINP and single ELF were 0.582 (95% CI 0.363-0.801) and
      0.693 (95% CI 0.482-0.904), respectively, for mild fibrosis; and 0.667 (95% CI
      0.363-0.971) and 0.806 (95% CI 0.564-1.000) for at least moderate fibrosis.
      CONCLUSIONS: This pilot study suggests that ELF may be at least equivalent or
      possibly superior to PIIINP in the detection of liver fibrosis in patients with
      psoriasis treated with methotrexate, and supports further investigations into the
      performance of ELF in this clinical setting.

PMID- 24942273
TI  - Researchers focus on recovery in schizophrenia.

PMID- 24942272
TI  - Dysregulation of myelopoiesis by chronic alcohol administration during early SIV
      infection of rhesus macaques.
AB  - BACKGROUND: Chronic alcohol intoxication suppresses immune function and increases
      osteoporosis risk suggesting bone-tissue cytotoxicity. Human immunodeficiency
      virus infection leads to similar impairments. This study investigated the effects
      of chronic alcohol administration during the early stage of simian
      immunodeficiency virus (SIV) infection on hematopoietic stem and progenitor cells
      (HSPCs) and their differentiated progeny in the bone marrow and peripheral blood
      of rhesus macaques. METHODS: Rhesus macaques were administered alcohol or sucrose
      daily for a period of 3 months prior to intrarectal inoculation with 250 TCID50
      of SIVmac251 . Bone marrow aspirates and blood samples were taken prior to and 2
      weeks after SIV infection. Bone marrow cells (BMCs) were assessed using flow
      cytometric phenotyping for upstream HSPCs and for differentiated cells of the
      monocyte-granulocyte lineages. Likewise, cells were quantitated in peripheral
      blood. RESULTS: Of the bone marrow HSPCs, only the common lymphoid progenitor
      (CLP) was altered by alcohol administration pre-SIV (38 +/- 9.4/10(6) BMCs vs.
      226 +/- 64.1/10(6) BMCs, sucrose vs. alcohol). Post-SIV, the frequency of CLPs in
      the bone marrow of alcohol-administered macaques decreased compared with the
      sucrose-administered macaques (107 +/- 47.6/10(6) BMCs vs. 43 +/- 16.3/10(6)
      BMCs). However, marrow mature cells of the monocyte lineage, specifically
      macrophages and osteoclast progenitors, were increased by both chronic alcohol
      administration and SIV infection (287% and 662%, respectively). As expected,
      mature cells such as granulocytes (polymorphonuclear cells), B cells, and CD4+ T
      cells in the peripheral blood were decreased by SIV infection (37 to 62% decline
      from preinfection), but not affected after 3 months of chronic alcohol
      administration. CONCLUSIONS: Chronic alcohol administration disrupts
      myelomonocytic development in the bone marrow during the early period of SIV
      infection promoting macrophage and osteoclast lineages. We predict this shift in
      CLP:macrophage/osteoclast balance creates an environment that favors bone
      resorption and immunosuppression.

PMID- 24942274
TI  - Concurrent systemic therapy with radiotherapy for the treatment of poor-risk
      patients with unresectable stage III non-small-cell lung cancer: a review of the
      literature.
AB  - BACKGROUND: There is no consensus on the therapeutic approach to poor-risk
      patients with unresectable stage III non-small-cell lung cancer (NSCLC), despite
      the increasing number of these patients in current clinical practice. In terms of
      survival, the combination of concurrent systemic therapy with standard
      radiotherapy might be advantageous over radiotherapy alone. The purpose of this
      review is to ascertain the feasibility, safety and efficacy of the combination of
      concurrent systemic therapy and standard radiotherapy in these patients. METHODS:
      A computer-based literature search was carried out using PubMed and Science
      Direct for relevant publications; data reported at major conferences in abstract
      form were also included. RESULTS: In unresectable stage III NSCLC, advanced age,
      poor performance status, weight loss and comorbidities are factors that influence
      treatment options and disease outcomes in clinical practice. Prospective studies
      including poor-risk patients have been reviewed. Trials specifically recruiting
      poor-risk patients have been separated into those using chemotherapy and those
      using targeted agents with or without chemotherapy. Only two phase III studies
      specifically including poor-risk patients have been published. Some recent
      studies suggested that tolerable radio-sensitizing therapy combined with
      radiotherapy can provide longer survival outcomes than those reported earlier
      with chemo-radiotherapy or with radiotherapy alone. CONCLUSIONS: There is an
      unmet need to develop well-designed clinical trials with tolerable combinations
      of systemic therapy and radiotherapy specifically tailored to this lung cancer
      population. Such trials should incorporate careful comorbidity measurement and,
      in older adults, a validated geriatric assessment.

PMID- 24942276
TI  - Netupitant and palonosetron (NEPA): a winning team in the race for the optimal
      treatment of chemotherapy-induced nausea and vomiting?

PMID- 24942275
TI  - Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation
      status by next-generation sequencing: findings from the CAPRI-GOIM trial.
AB  - BACKGROUND: Treatment with antiepidermal growth factor receptor (anti-EGFR)
      monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC)
      patients with RAS wild-type tumors. Next-generation sequencing (NGS) allows the
      assessment in a single analysis of a large number of gene alterations and might
      provide important predictive and prognostic information. PATIENTS AND METHODS: In
      the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line
      FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to
      search for mutations in 22 genes involved in colon cancer. RESULTS: Objective
      responses in the NGS cohort were observed in 104/182 patients [overall response
      rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4%] with a median
      progression-free survival (mPFS) of 9.8 (95% CI 8.7-11.5) months. NGS analysis
      was successfully completed in all 182 samples. One or more gene mutations (up to
      five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of
      206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples,
      defined as wild type by local laboratory assessment. Frequently mutated genes
      were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons
      9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of
      62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2-12.8) months in
      patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI
      39.9-57.5%) with mPFS of 8.9 (95% CI 7.4-9.6) months in patients with KRAS or
      NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or
      PIK3CA mutations showed a worse outcome, although this might be due to a
      prognostic effect. CONCLUSIONS: This study demonstrates that NGS analysis in mCRC
      is feasible, reveals high level of intra and intertumor heterogeneity, and
      identifies patients that might benefit of FOLFIRI plus cetuximab treatment.

PMID- 24942278
TI  - 'Fracture incidence after 3 years of aromatase inhibitor therapy'.

PMID- 24942277
TI  - S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III
      study (ACTS-CC trial).
AB  - BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been
      demonstrated in treating various gastrointestinal cancers, including metastatic
      colon cancer, when administered as monotherapy or in combination chemotherapy. We
      conducted a randomized phase III study investigating the efficacy of S-1 as
      adjuvant chemotherapy for colon cancer by evaluating its noninferiority to
      tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20
      80 years with curatively resected stage III colon cancer were randomly assigned
      to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV
      (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses).
      The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A
      total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively)
      were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5%
      in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in
      the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval:
      0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified
      log-rank test, P < 0.001). In the subgroup analysis, no significant interactions
      were identified between the major baseline characteristics and the treatment
      groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer
      was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new
      treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV:
      NCT00660894.

PMID- 24942279
TI  - Impact of age and gender on microvascular function.
AB  - BACKGROUND: Microcirculatory function can be assessed by postocclusive reactive
      hyperaemia (PORH) using laser Doppler fluxmetry. Previous studies have shown that
      PORH reveals microvascular damage at an early stage. In particular, at younger
      ages, PORH might depend on age and gender. To implement PORH into a larger scale
      of clinical studies, one has to be aware of the influence of age and gender on
      microcirculation. The aim of this study was to assess the impact of age and
      gender on microcirculatory function during adolescence. MATERIALS AND METHODS:
      Within the scope of an epidemiological project, 896 children and adolescents
      underwent assessment of PORH by laser Doppler fluxmetry. Microcirculatory
      parameters during PORH (baseline perfusion, biological zero, peak perfusion, time
      to peak perfusion and recovery time) were analysed in relation to age (by
      tertiles) and gender. RESULTS: Baseline perfusion, biological zero and peak
      perfusion were lower in children/adolescents in the upper age tertile (12.3-18.1
      years) than in the middle (9.8-12.2 years) and lower (4.3-9.7 years) age tertiles
      (P < 0.0001). In the total of participants, baseline perfusion, biological zero
      and peak perfusion were higher in males than in females (P < 0.0001). Analysing
      microcirculatory parameters as a function of age and gender, the sex differences
      were only apparent in the upper and the middle age tertiles, but not in the
      lower. CONCLUSIONS: During adolescence, PORH is a function of age. At higher age,
      microvascular reactivity considerably depends on gender, whereas no sex
      differences are present at younger ages.

PMID- 24942280
TI  - Modification of commercially available image analysis software for semi-automated
      qualitative analysis of axon regeneration and myelination in the rat sciatic
      nerve.
AB  - BACKGROUND: Manual measurement of three routine parameters of axon regeneration
      and myelination, such as axon counts, axon caliber and G-Ratio, is tedious and
      time consuming. An automated or semi-automated computer program could improve the
      efficiency of this process. The concern, however, is that the automated method
      will lack the accuracy of manual counting and measuring. METHOD: We introduce
      semi-automated axon analysis software utilizing customized Image Pro Plus
      software designed to identify, count, and measure axons and their surrounding
      myelin sheaths. Histologic specimens were subsequently analyzed using either
      conventional manual techniques (manual counting and computer assisted
      measurements) or this semi-automated software (software performed counting and
      measurements with human supervision and adjustment of axon identification).
      RESULTS: G-Ratios, axon numbers, and axon diameter values did not differ between
      the two methods though the semi-automated method took approximately 50% less
      time. COMPARISON WITH EXISTING METHODS: Other described semi-automated nerve
      analysis tools require complex, original software development. CONCLUSIONS:
      Commercially available software can be modified to improve nerve histomorphology
      analysis time while maintaining accuracy.

PMID- 24942281
TI  - Rydberg atoms in hollow-core photonic crystal fibres.
AB  - The exceptionally large polarizability of highly excited Rydberg atoms-six orders
      of magnitude higher than ground-state atoms--makes them of great interest in
      fields such as quantum optics, quantum computing, quantum simulation and
      metrology. However, if they are to be used routinely in applications, a major
      requirement is their integration into technically feasible, miniaturized devices.
      Here we show that a Rydberg medium based on room temperature caesium vapour can
      be confined in broadband-guiding kagome-style hollow-core photonic crystal
      fibres. Three-photon spectroscopy performed on a caesium-filled fibre detects
      Rydberg states up to a principal quantum number of n=40. Besides small energy
      level shifts we observe narrow lines confirming the coherence of the Rydberg
      excitation. Using different Rydberg states and core diameters we study the
      influence of confinement within the fibre core after different exposure times.
      Understanding these effects is essential for the successful future development of
      novel applications based on integrated room temperature Rydberg systems.

PMID- 24942282
TI  - The effect of using high facilitation when implementing the Gold Standards
      Framework in Care Homes programme: a cluster randomised controlled trial.
AB  - BACKGROUND: The provision of quality end-of-life care is increasingly on the
      national agenda in many countries. In the United Kingdom, the Gold Standards
      Framework for Care Homes programme has been promoted as a national framework for
      improving end-of-life care. While its implementation is recommended, there are no
      national guidelines for facilitators to follow to undertake this role. AIM: It
      was hypothesised that action learning alongside high facilitation when
      implementing the Gold Standards Framework for Care Homes programme will result in
      a reduced proportion of hospital deaths for residents and improvement in the care
      home staff ability to facilitate good end-of-life care. DESIGN: A cluster
      randomised controlled trial where 24 nursing homes received high facilitation to
      enable them to implement the Gold Standards Framework for Care Homes programme.
      The managers of 12 nursing homes additionally took part in action learning sets.
      A third group (14 nursing homes) received the 'standard' Gold Standards Framework
      for Care Homes facilitation available in their locality. SETTING/PARTICIPANTS: In
      total, 38 nursing homes providing care for frail older people, their deceased
      residents and their nurse managers. RESULTS: A greater proportion of residents
      died in those nursing homes receiving high facilitation and action learning but
      not significantly so. There was a significant association between the level of
      facilitation and nursing homes completing the Gold Standards Framework for Care
      Homes programme through to accreditation. Year-on-year change occurred across all
      outcome measures. CONCLUSION: There is a danger that without national guidelines,
      facilitation of the Gold Standards Framework for Care Homes programme will vary
      and consequently so will its implementation. The nurse manager of a care home
      must be actively engaged when implementing the Gold Standards Framework for Care
      Homes programme.

PMID- 24942283
TI  - How do general end-of-life treatment goals and values relate to specific
      treatment preferences? a population-based study.
AB  - BACKGROUND: There is a lack of research on the relationship between general end
      of-life goals and values and preferences for specific life-sustaining treatments.
      AIM: To examine agreement between Dutch older people's general end-of-life goals
      and specific life-sustaining treatment preferences. DESIGN: Participants
      identified general end-of-life goals in an interview and preferences for four
      life-sustaining treatments in hypothetical cancer and dementia scenarios in a
      separate questionnaire. Agreement between general goals and specific treatment
      preferences was calculated. SETTING/PARTICIPANTS: In total, 1818 older people
      from 11 representative Dutch municipalities participated in the study. RESULTS:
      In total, 1168 (response rate 73%) answered questions on general end-of-life and
      specific treatment preferences. Agreement between a desire to live as long as
      possible, irrespective of health problems, and a preference for life-sustaining
      treatments ranged from 51% to 76% in cancer and 41% to 60% in dementia scenarios,
      depending on the treatment. Agreement between a desire for a shorter life, if
      without major health problems, and a preference to forgo treatments ranged from
      61% to 79% in cancer and 75% to 88% in dementia scenarios. CONCLUSION: For a
      sizable minority of participants, specific treatment preferences did not agree
      with their general end-of-life goals. The more frequent desire to forgo
      treatments in case of dementia than cancer suggests that physical deterioration
      is more acceptable than cognitive decline. The findings underline the importance
      of discussing general care goals, different end-of-life scenarios and the risks
      and burdens of treatments to frame discussions of more specific treatment
      preferences.

PMID- 24942284
TI  - Why exercise is good for your brain: A closer look at the underlying mechanisms
      suggests that some sports, especially combined with mental activity, may be more
      effective than others.

PMID- 24942285
TI  - Histomolecular interpretation of pleomorphic adenomas of the salivary gland by
      matrix-assisted laser desorption ionization imaging and spatial segmentation.
AB  - BACKGROUND: Despite efforts in localization of key proteins using
      immunohistochemistry, the complex proteomic composition of pleomorphic adenomas
      has not yet been characterized. Matrix-assisted laser desorption/ionization
      imaging mass spectrometry (MALDI imaging) allows label-free and spatially
      resolved detection of hundreds of proteins directly from tissue sections and of
      histomorphological regions by finding colocalized molecular signals. Spatial
      segmentation of MALDI imaging data is an algorithmic method for finding regions
      of similar proteomic composition as functionally similar regions. METHODS: We
      investigated 2 pleomorphic adenomas by applying spatial segmentation to the MALDI
      imaging data of tissue sections. RESULTS: The spatial segmentation subdivided the
      tissue in a good accordance with the tissue histology. Numerous molecular signals
      colocalized with histologically defined tissue regions were found. CONCLUSION:
      Our study highlights the cellular transdifferentiation within the pleomorphic
      adenoma. It could be shown that spatial segmentation of MALDI imaging data is a
      promising approach in the emerging field of digital histological analysis and
      characterization of tumors.

PMID- 24942286
TI  - Prognostic significance of mean platelet volume in diabetic patients with ST
      elevation myocardial infarction.
AB  - PURPOSE: Mean platelet volume (MPV) is a universally available parameter with
      routine blood counts. It has been linked to many cardiovascular risk factors. MPV
      is a marker of platelet size and activity and has been linked to poor prognosis
      following STEMI. There has been an increasing number of reports linking diabetes
      mellitus (DM) to platelet dysfunction. The aim of the study was to examine the
      association between admission MPV and clinical outcomes in patients with DM and
      STEMI undergoing primary percutaneous coronary intervention (PCI). The secondary
      objective of the study was to evaluate whether this index can be used to
      determine the long-term prognosis. METHODS: A total of 1,557 patients with STEMI
      undergoing primary PCI were enrolled and divided into two groups depending on
      their diabetes mellitus status: Group 1 - patients with diabetes mellitus (N=539)
      and Group 2 - patients without diabetes mellitus (N=1018). RESULTS: MPV and peak
      CK-MB concentration were higher in diabetic patients as compared to non-diabetic
      patients. In diabetic patients, MPV was positively correlated with admission
      Killip class and negatively correlated with time to death during follow-up,
      initial TIMI flow, final TIMI flow, and erythrocyte count. In non-diabetic
      patients, MPV was positively correlated with the number of diseased coronary
      arteries, admission Killip class, and negatively correlated with time to death
      during follow-up and initial TIMI flow. ROC analysis revealed high diagnostic
      value of MPV in predicting in-hospital and one-year mortality. MPV cut-off level
      was lower for diabetic patients compared to non-diabetic patients. CONCLUSIONS:
      Diabetic patients had higher MPV than non-diabetic patients. Both in diabetic and
      non-diabetic patients MPV proved to have good prognostic value for in-hospital
      and late mortality. MPV cut-off value for predicting mortality was lower in
      diabetic patients. Mortality rate was the highest in the fourth quartiles of MPV
      in both study groups.

PMID- 24942288
TI  - Tuning the growth mode of nanowires via the interaction among seeds, substrates
      and beam fluxes.
AB  - The growth mechanism of semiconductor nanowires is still an argument of high
      interest, and it is becoming clearer, investigation after investigation, that
      simple pictures fail to describe the complex behaviors observed under different
      growth conditions. We report here on the growth of semiconductor nanowires,
      maintaining control over the chemical composition and the physical state of the
      metallic seeds, and tuning the growth mechanism by varying the growth conditions.
      We focused on Au-assisted ZnSe nanowires grown by molecular beam epitaxy on
      GaAs(111)B substrates. We show that at sufficiently high temperatures, the Au
      seed is strongly affected by the interaction with the substrate and that nanowire
      growth can occur through two different mechanisms, which have a strong impact on
      the nanowire's morphology and crystal quality. In particular, ZnSe NWs may
      exhibit either a uniformly oriented, straight morphology when the nanoparticle
      seed is liquid, or a kinked, worm-like shape when the nanoparticle seed is
      switched to a solid phase. This switch, which tunes the nanowire growth
      mechanism, is achieved by controlling the Zn-to-Se beam pressure ratio at the Au
      seed surface. Our results allow a deeper understanding of particle-assisted
      nanowire growth, and an accurate control of nanowire morphology via the control
      of the growth mechanism. 

PMID- 24942287
TI  - Post-transcriptional regulation of the tumor suppressor miR-139-5p and a network
      of miR-139-5p-mediated mRNA interactions in colorectal cancer.
AB  - MicroRNAs play key roles in many biological processes, and are frequently
      dysregulated in tumor cells. However, there are few studies on how microRNAs are
      dysregulated. miR-139-5p, an important tumor suppressor, is often underexpressed
      in gastrointestinal cancer cells. Here, we describe post-transcriptional
      regulation of this intronic microRNA in human colorectal cancer. miR-139-5p is
      expressed independently of its overexpressed host gene PDE2A in colorectal cancer
      tissues and cell lines. The miR-139-5p target genes IGF1R, ROCK2 and RAP1B exert
      regulatory effects on the miR-139-5p expression level, relying on their ability
      to compete for miR-139-5p binding. These overexpressed target genes also regulate
      each others' protein levels through 3'-UTRs, thus regulating tumor cell growth
      and motility properties. Our study provides a mechanistic, experimentally
      validated rationale for intronic microRNA dysregulation in colorectal cancer,
      revealing novel oncogenic roles of IGF1R, ROCK2 and RAP1B 3'-UTRs. 

PMID- 24942289
TI  - Molecular dynamics investigations of liquid-vapor interaction and adsorption of
      formaldehyde, oxocarbons, and water in graphitic slit pores.
AB  - Formaldehyde exposure has been associated with several human cancers, including
      leukemia and nasopharyngeal carcinoma, motivating the present investigation on
      the microscopic adsorption behaviors of formaldehyde in multi-component-mixture
      filled micropores. Molecular dynamics (MD) simulation was used to investigate the
      liquid-vapor interaction and adsorption of formaldehyde, oxocarbons, and water in
      graphitic slit pores. The effects of the slit width, system temperature,
      concentration, and the constituent ratio of the mixture on the diffusion and
      adsorption properties are studied. As a result of interactions between the
      components, the z-directional self-diffusivity (D(z)) in the mixture
      substantially decreased by about one order of magnitude as compared with that of
      pure (single-constituent) adsorbates. When the concentration exceeds a certain
      threshold, the D(z) values dramatically decrease due to over-saturation inducing
      barriers to diffusion. The binding energy between the adsorbate and graphite at
      the first adsorption monolayer is calculated to be 3.99, 2.01, 3.49, and 2.67
      kcal mol(-1) for CO2, CO, CH2O, and H2O, respectively. These values agree well
      with those calculated using the density functional theory coupled cluster method
      and experimental results. A low solubility of CO2 in water and water preferring
      to react with CH2O, forming hydrated methanediol clusters, are observed. Because
      the cohesion in a hydrated methanediol cluster is much higher than the adhesion
      between clusters and the graphitic surface, the hydrated methanediol clusters
      were hydrophobic, exhibiting a large contact angle on graphite.

PMID- 24942290
TI  - A newly discovered linkage between proteoglycans and hair biology: decorin acts
      as an anagen inducer.
AB  - Proteoglycans have been suggested to play pivotal roles in hair biology. Decorin
      is a prototypical member of the small leucine-rich proteoglycan family, which is
      involved in numerous biological processes. However, the role of decorin in the
      hair cycle has not been elucidated. Moreover, the effects of decorin on the
      activities of many growth factors are complex, and it is hard to predict whether
      decorin would affect hair growth or the hair cycle positively or negatively. Jing
      et al. focused on the potential role of decorin in the hair cycle and found that
      decorin is highly expressed in the epidermis, in hair follicle epithelial cells
      and in dermal papilla cells in the anagen phase. The expression of decorin was
      decreased during catagen to telogen, except for the bulge region. Exogenous
      administration of decorin accelerated anagen and delayed catagen transition as a
      positive regulator of the hair cycle. Because TGF-beta is one of the androgen
      induced pathogenic factors in androgenetic alopecia, this study provides clues to
      understand the pathogenesis and new therapeutic targets of hair loss. 

PMID- 24942291
TI  - Melatonin reduces cardiac remodeling and improves survival in rats with
      isoproterenol-induced heart failure.
AB  - Melatonin was previously shown to reduce blood pressure and left ventricular (LV)
      remodeling in several models of experimental heart damage. This study
      investigated whether melatonin prevents LV remodeling and improves survival in
      isoproterenol-induced heart failure. In the first experiment, four groups of 3
      month-old male Wistar rats (12 per group) were treated for 2 wk as follows:
      controls, rats treated with melatonin (10 mg/kg/day) (M), rats treated with
      isoproterenol (5 mg/kg/day intraperitoneally the second week) (Iso), and rats
      treated with melatonin (2 wk) and isoproterenol (the second week) in
      corresponding doses (IsoM). In the second experiment, 30 rats were treated with
      isoproterenol and 30 rats with isoproterenol plus melatonin for a period of 28
      days and their mortality was investigated. Isoproterenol-induced heart failure
      with hypertrophy of the left and right ventricles (LV, RV), lowered systolic
      blood pressure (SBP) and elevated pulmonary congestion. Fibrotic rebuilding was
      accompanied by alterations of tubulin level in the LV and oxidative stress
      development. Melatonin failed to reduce the weight of the LV or RV; however, it
      curtailed the weight of the lungs and attenuated the decline in SBP. Moreover,
      melatonin decreased the level of oxidative stress and of insoluble and total
      collagen and partly prevented the beta-tubulin alteration in the LV. Most
      importantly, melatonin reduced mortality and prolonged the average survival time.
      In conclusion, melatonin exerts cardioprotective effects and improves outcome in
      a model of isoproterenol-induced heart damage. The antiremodeling effect of
      melatonin may be of potential benefit in patients with heart failure. 

PMID- 24942292
TI  - Changes in resting heart rate variability across the menstrual cycle.
AB  - Heart rate variability (HRV) is a noninvasive indicator of autonomic control.
      This study examines HRV changes across a normal menstrual cycle and proposes a
      novel piecewise function controlling for the effects of breathing on HRV spectral
      parameters. A resting ECG was collected from 13 women at five points in their
      menstrual cycle. Both heart rate and breathing rate increased across the cycle (p
      < .01) while time-domain variability decreased (p = .04). Use of the piecewise
      function for breathing rate in HRV spectral analysis was confirmed by a
      substantial increase in model goodness-of-fit. HRV spectral parameters,
      controlled for breathing with the piecewise function, confirm that the decrease
      in variability is likely due to a parasympathetic withdrawal, since high
      frequency HRV decreases (p = .02).

PMID- 24942293
TI  - Association of hyponatremia to diuretic response and incidence of increased serum
      creatinine levels in hospitalized patients with acute decompensated heart
      failure.
AB  - OBJECTIVES: Although hyponatremia is a prognostic factor in acute heart failure
      (AHF), its influence on the acute clinical course of heart failure is unknown.
      Our objective was to evaluate the association of hyponatremia with diuretic
      response, renal function, and clinical outcomes in AHF. METHODS: A retrospective
      study included 499 hospitalized AHF patients treated with intravenous loop
      diuretics for >=48 h. Patients were grouped by nadir sodium concentrations
      (normonatremic, NN) >=135 mEq/l, (mild hyponatremia, MHN) 130-134 mEq/l, and
      (moderate to severe hyponatremia, MSHN) <130 mEq/l. Association to diuretic
      response and clinical outcome was assessed. RESULTS: The incidence of
      hyponatremia was 54% (36% MHN, 18% MSHN). Maximum diuretic dose (furosemide
      equivalents: NN 84 +/- 132 mg/day vs. MHN 114 +/- 165 mg/day vs. MSHN 249 +/- 450
      mg/day, p < 0.001) and incidence of diuretic regimen escalation (NN 11% vs. MHN
      16% vs. MSHN 44%, p < 0.001) were significantly higher in patients experiencing
      hyponatremia. Hyponatremia was also associated with a higher incidence of acute
      increases in serum creatinine (NN 27% vs. MHN 45% vs. MSHN 63%, p < 0.001),
      greater increases in blood urea nitrogen, longer hospital stay, and higher
      mortality. Outcome disparities to NN patients were similar whether hyponatremia
      was acute or present upon admission. CONCLUSIONS: Acute or admission
      hyponatremia, especially <130 mEq/l, in AHF patients is associated with greater
      diuretic requirements, higher incidence of serum creatinine increases, and a
      poorer outcome. Alternative treatments warrant evaluation in these patients.

PMID- 24942294
TI  - Elkonyxis associated with habit-tic deformity: two case reports.

PMID- 24942295
TI  - Distribution of the axillary nerve to the subacromial bursa and the area around
      the long head of the biceps tendon.
AB  - PURPOSE: Patients with a shoulder disorder often complain of pain on the anterior
      or lateral aspect of the shoulder. Such pain has been thought to originate from
      the suprascapular nerve. However, taking into consideration the distinctive
      course of the axillary nerve, the axillary nerve is likely to supply branches to
      the structure around the shoulder joint. This study was conducted to clarify the
      division, course, and distribution of the branches which originate from the
      axillary nerve and innervate structures around the shoulder joint. METHODS: The
      division, course, and distribution of the branches which originate from the
      axillary nerve and innervate structures around the shoulder joint were examined
      macroscopically by dissecting 20 shoulders of 10 adult Japanese cadavers.
      RESULTS: The thin branches from the anterior branch of the axillary nerve were
      distributed to the subacromial bursa and the area around the long head of the
      biceps tendon. The branches from the main trunk of the axillary nerve or the
      branch to the teres minor muscle were distributed to the infero-posterior part of
      the shoulder joint. CONCLUSION: The pain on the anterior or lateral aspect of the
      shoulder, which has been thought to originate from the suprascapular nerve, might
      be related to the thin branches which originate from the axillary nerve and
      innervate the subacromial bursa and the area around the long head of the biceps
      tendon. CLINICAL RELEVANCE: These results would be useful to consider the cause
      of the shoulder pain or to prevent the residual pain after the biceps tenodesis.

PMID- 24942296
TI  - Effect of two different preparations of platelet-rich plasma on synoviocytes.
AB  - PURPOSE: To analyse the modifications induced by two different platelet-rich
      plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting
      changes in gene expression of factors involved in joint physiopathology. METHODS:
      OA synoviocytes were cultured for 7 days in medium with different concentrations
      of either P-PRP (a pure platelet concentrate without leucocytes but with a
      limited number of platelets), L-PRP (a higher platelet concentrate containing
      leucocytes) or platelet-poor plasma (PPP). Gene expression of interleukin (IL)
      1beta, IL-6, IL-8/CXCL8, tumour necrosis factor alpha, IL-10, IL-4, IL-13,
      metalloproteinase-13, tissue inhibitor of metalloproteinase (TIMP)-1, (TIMP)-3,
      (TIMP)-4, vascular endothelial growth factor, transforming growth factor beta1,
      fibroblast growth factor (FGF)-2, hepatocyte growth factor (HGF), hyaluronic acid
      (HA) synthases (HAS)-1, (HAS)-2, and (HAS)-3 was analysed by RT-PCR. HA
      production was determined in culture supernatants by ELISA. RESULTS: IL-1beta, IL
      8 and FGF-2 were significantly induced by L-PRP compared to both P-PRP and PPP;
      HGF was down-modulated by L-PRP versus both P-PRP and PPP, and an inverse dose
      response influence was shown for all preparations. Expression level of TIMP-4 was
      lower in the presence of L-PRP compared with P-PRP. HA production and HAS gene
      expression did not seem to be modulated by PRP. CONCLUSIONS: L-PRP is able to
      sustain the up-regulation of proinflammatory factors, (IL-1beta, IL-8 and FGF-2),
      together with a down-modulation of HGF and TIMP-4 expression, two factors that
      have been recognized as anti-catabolic mediators in cartilage, thus supporting
      the need to further optimize the PRP preparations to be applied in clinical
      practice.

PMID- 24942297
TI  - New hydrogen-evolution heteronanostructured photocatalysts: Pt-Nb3 O7 (OH) and Cu
      Nb3 O7 (OH).
AB  - Nanorods of triniobium hydroxide heptaoxide, Nb3 O7 (OH), were synthesized by
      means of a hydrothermal method. Subsequently, Pt and CuO nanoparticles were
      introduced on the surface of Nb3 O7 (OH) nanorods by a microwave-assisted
      solvothermal nucleation and growth technique. The resulting Pt- and CuO-decorated
      Nb3 O7 (OH) nanorods demonstrated uniform particle dispersion and were fully
      characterized by X-ray diffraction, electron microscopy, and spectroscopic
      analysis. Furthermore, the solar-powered photocatalytic hydrogen production
      properties of these heteronanostructures were studied. The solar-driven H2
      formation rate over Pt-Nb3 O7 (OH) was determined to be 710.4 +/- 1.7 MUmol g(-1)
      h(-1) with a quantum efficiency of phi=5.40% at lambda=380 nm. Interestingly, the
      as-prepared CuO-Nb3 O7 (OH) heteronanostructure was found to be inactive under
      solar irradiation during an induction phase, whereupon it undergoes an in situ
      photoreduction process to form the photocatalytically active Cu-Nb3 O7 (OH). This
      restructuring process was monitored by an in situ measurement of the time
      evolution of the optical absorption spectra. The solar-powered H2 production for
      the restructured compound was determined to be 290.3 +/- 5.1 MUmol g(-1) h(-1) .

PMID- 24942299
TI  - Global rules for global health: why we need an independent, impartial WHO.

PMID- 24942300
TI  - Axial post-contrast computed tomogram at the level of the aortic arch.

PMID- 24942301
TI  - Ilora Finlay: Hooked on candy crush.

PMID- 24942298
TI  - Relapsed Hodgkin lymphoma: management strategies.
AB  - Although Hodgkin lymphoma (HL) is largely curable with first-line therapy,
      approximately one-third of patients will not have a complete response to
      frontline treatment or will subsequently relapse. Only 50% of these patients will
      be effectively salvaged with conventional therapies. The prognosis is
      particularly poor for those patients with chemotherapy refractory disease, who
      are unable to obtain even transient disease control, and for patients who relapse
      following high dose chemotherapy and autologous stem cell transplant. In this
      review, we summarize the most recent updates on the management of patients with
      relapsed HL, the role of novel therapies such as brentuximab vedotin, and an
      overview of promising new agents currently under investigation. We also discuss
      the role of consolidation strategies such as high-dose chemotherapy and
      autologous stem cell transplant, and reduced-intensity allogeneic hematopoietic
      stem cell transplant, and the need for new strategies in the elderly patient
      population.

PMID- 24942302
TI  - MPs urge government to act quickly to strengthen health regulation.

PMID- 24942303
TI  - New European legislation on clinical trials is published.

PMID- 24942304
TI  - Washable and wear-resistant superhydrophobic surfaces with self-cleaning property
      by chemical etching of fibers and hydrophobization.
AB  - Superhydrophobic poly(ethylene terephthalate) (PET) textile surfaces with a self
      cleaning property were fabricated by treating the microscale fibers with alkali
      followed by coating with polydimethylsiloxane (PDMS). Scanning electron
      microscopy analysis showed that alkali treatment etched the PET and resulted in
      nanoscale pits on the fiber surfaces, making the textiles have hierarchical
      structures. Coating of PDMS on the etched fibers affected little the roughening
      structures while lowered the surface energy of the fibers, thus making the
      textiles show slippery superhydrophobicity with a self-cleaning effect.
      Wettability tests showed that the superhydrophobic textiles were robust to
      acid/alkaline etching, UV irradiation, and long-time laundering. Importantly, the
      textiles maintained superhydrophobicity even when the textiles are ruptured by
      severe abrasion. Also colorful images could be imparted to the superhydrophobic
      textiles by a conventional transfer printing without affecting the
      superhydrophobicity. 

PMID- 24942305
TI  - Where do peer reviewers come from?

PMID- 24942306
TI  - Mandating audio-video recording of informed consent: are we right in enforcing
      this?
AB  - Medicines are the result of experimentation carried out in animals and humans.
      However, there are numerous instances in the history of medicine where humans
      were subjected to undue risks and abuses, requiring regulations for their safety.
      Idea of informed consent has found its presence in medical literature from the
      times of Hippocratic Oath propagating principles of '...never do harm to anyone'
      and physician directed care of patients. This was revived in post-world war II
      era in the form of Nuremberg code and the declaration of Helsinki in response to
      various debilitating experimentations done on prisoners in concentration camps
      and elsewhere. Complete information and voluntary participation forms the ethical
      tenets of these acts and the same has been reflected in various guidelines
      enacted worldwide, which are sufficient to make sure that patient consent is
      obtained in fair and just manner. Despite this, there have been undesirable
      lapses in the conduct of clinical trials. This situation worsens, when
      intentional lapses in conduct of trial hamper the ability of socially and
      economically disadvantaged communities in developing countries to make free and
      informed decision.

PMID- 24942307
TI  - Uric acid as a cardiorenal risk factor - ready for prime-time?
AB  - Patients with cardiac morbidity are known to have increased risk of developing
      renal disease, and vice versa. Cardiorenal syndrome is a general term describing
      concomitant cardiac and renal dysfunction, and recently there has been renewed
      interest in the role of uric acid (UA) in its pathophysiology and management.
      There is evidence to suggest that UA-lowering drugs, such as the xanthine oxidase
      (XO) inhibitors allopurinol and Febuxostat, may not only retard deteriorating
      renal function in the context of chronic kidney disease (CKD) but also confer
      protective cardiovascular effects. As these diseases represent considerable
      health burdens, this evidence merits evaluation to determine whether or not
      hyperuricaemia is a cardiorenal risk factor that necessitates intervention and if
      existing pharmacological agents are sufficiently efficacious.

PMID- 24942308
TI  - Impact of changes to reimbursement of fixed combinations of inhaled
      corticosteroids and long-acting beta2 -agonists in obstructive lung diseases: a
      population-based, observational study.
AB  - BACKGROUND: In 2010, the Icelandic government introduced a new cost-saving policy
      that limited reimbursement of fixed inhaled corticosteroid/long-acting beta2 
      agonist (ICS/LABA) combinations. METHODS: This population-based, retrospective,
      observational study assessed the effects of this policy change by linking
      specialist/primary care medical records with data from the Icelandic
      Pharmaceutical Database. The policy change took effect on 1 January 2010 (index
      date); data for the year preceding and following this date were analysed in 8241
      patients with controlled/partly controlled asthma and/or chronic obstructive
      pulmonary disease (COPD) who had been dispensed an ICS/LABA during 2009. Oral
      corticosteroid (OCS) and short-acting beta2 -agonist (SABA) use, and healthcare
      visits, were assessed pre- and post-index. RESULTS: The ICS/LABA reimbursement
      policy change led to 47.8% fewer fixed ICS/LABA combinations being dispensed
      during the post-index period among patients whose asthma and/or COPD was
      controlled/partly controlled during the pre-index period. Fewer ICS
      monocomponents were also dispensed. A total of 48.6% of patients were no longer
      receiving any respiratory medications after the policy change. This was
      associated with reduced disease control, as demonstrated by more healthcare
      visits (44.0%), and more OCS (76.3%) and SABA (51.2%) dispensations. CONCLUSIONS:
      Overall, these findings demonstrate that changes in healthcare policy and
      medication reimbursement can directly impact medication use and, consequently,
      clinical outcomes and should, therefore, be made cautiously.

PMID- 24942309
TI  - Screening for cardiovascular risk factors in patients admitted for acute coronary
      syndrome.

PMID- 24942311
TI  - Effects of an oral nitric oxide supplement on functional capacity and blood
      pressure in adults with prehypertension.
AB  - Nitric oxide (NO) is an integral molecule especially important in the regulation
      of the cardiovascular system. Literature indicates that the number of studies
      continues to grow with regard to the effects of NO on cardiovascular disease and
      hypertension. "Prehypertension" is the clinical stage leading to hypertension.
      Diet and lifestyle modifications are the only treatment options for
      prehypertension. The objective of this study was to determine the effects of oral
      NO supplementation on blood pressure in patients with clinical prehypertension.
      This pilot phase study evaluated the effect of an orally disintegrating lozenge
      that generates NO in the oral cavity on blood pressure, functional capacity, and
      quality of life. Thirty patients with clinical prehypertension were recruited and
      enrolled in either the NO treatment or the placebo group over a 30-day period in
      an outpatient setting. Nitric oxide supplementation resulted in a significant
      decrease in resting blood pressure (138 +/- 12 mm Hg in systole and 84 +/- 5 mm
      Hg in diastole at baseline vs 126 +/- 12 mm Hg in systole and 78 +/- 4 mm Hg in
      diastole at follow-up, P < .001, vs baseline) and a significant increase in the
      achieved walking distance in the standard 6-minute walk test (596 +/- 214 meters
      at baseline vs 650 +/- 197 meters at follow-up, P < .005 vs baseline). Using a
      standardized questionnaire to assess quality of life, patients receiving NO
      supplementation showed improvement in the Physical Component Summary Score (PCS)
      and Mental Component Summary Score (MCS). Nitric oxide supplementation appears to
      lower blood pressure in patients with prehypertension and might be beneficial as
      a routine supplementation for cardiovascular protection. 

PMID- 24942310
TI  - Upregulation of IFN-gamma and IL-12 is associated with a milder form of
      hantavirus hemorrhagic fever with renal syndrome.
AB  - Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease
      characterized by acute onset, fever, malaise, and back pain. As the disease
      progresses, hemorrhagic disturbances and kidney dysfunctions predominate. The
      examination of tissue collected postmortem supports the premise that virus
      replication is not responsible for this pathology; therefore, it is widely
      believed that virus-induced immune responses lead to the clinical manifestations
      associated with HFRS. The overproduction of inflammatory cytokines is commonly
      reported in subjects with HFRS and has given rise to the hypothesis that a so
      called "cytokine storm" may play a pivotal role in the pathogenesis of this
      disease. Currently, supportive care remains the only effective treatment for
      HFRS. Our data show that serum levels of interferon (IFN)-gamma, interleukin (IL)
      10, CCL2, and IL-12 are upregulated in HFRS cases when compared to healthy
      controls and the level of upregulation is dependent on the phase and severity of
      the disease. Furthermore, we observed an association between the mild form of the
      disease and elevated serum levels of IFN-gamma and IL-12. Collectively, these
      observations suggest that the administration of exogenous IFN-gamma and IL-12 may
      provide antiviral benefits for the treatment of HFRS and, thus, warrants further
      investigations. 

PMID- 24942312
TI  - Torpor is not the only option: seasonal variations of the thermoneutral zone in a
      small primate.
AB  - The reddish-gray mouse lemur (Microcebus griseorufus) is one of only a few small
      mammals inhabiting the spiny forest of southwestern Madagascar. In this study we
      investigated the physiological adjustments which allow these small primates to
      persist under the challenging climatic conditions of their habitat. To this end
      we measured energy expenditure (metabolic rate) and body temperature of 24
      naturally acclimatized mouse lemurs, kept in outdoor enclosures, during different
      seasons (summer, winter, and the transition period between the two seasons).
      Mouse lemurs displayed two main physiological strategies to compensate seasonal
      and diurnal fluctuations of ambient temperature. On the one hand, individuals
      entered hypometabolism with decreasing ambient temperature (T a) during the
      transition period and winter, enabling them to save up to 21 % energy per day (92
      % per hour) compared with the normal resting metabolic rate at comparable T a. On
      the other hand, euthermic mouse lemurs also showed physiological adjustments to
      seasonality when resting: the lower critical temperature of the thermoneutral
      zone decreased from summer to winter by 7.5  degrees C, which allowed mouse
      lemurs to keep energy demands constant despite colder T as during winter. In
      addition, the basal metabolic rate was substantially lowered prior to the winter
      period, which facilitated accumulation of fat reserves. The combination of
      physiological modifications during euthermia in addition to hypometabolism, which
      can be individually adjusted according to external parameters and respective body
      condition, is important as it allows M. griseorufus to cope with the
      environmental variability of an energetically challenging habitat.

PMID- 24942314
TI  - Functional linear models for zero-inflated count data with application to
      modeling hospitalizations in patients on dialysis.
AB  - We propose functional linear models for zero-inflated count data with a focus on
      the functional hurdle and functional zero-inflated Poisson (ZIP) models. Although
      the hurdle model assumes the counts come from a mixture of a degenerate
      distribution at zero and a zero-truncated Poisson distribution, the ZIP model
      considers a mixture of a degenerate distribution at zero and a standard Poisson
      distribution. We extend the generalized functional linear model framework with a
      functional predictor and multiple cross-sectional predictors to model counts
      generated by a mixture distribution. We propose an estimation procedure for
      functional hurdle and ZIP models, called penalized reconstruction, geared towards
      error-prone and sparsely observed longitudinal functional predictors. The
      approach relies on dimension reduction and pooling of information across subjects
      involving basis expansions and penalized maximum likelihood techniques. The
      developed functional hurdle model is applied to modeling hospitalizations within
      the first 2 years from initiation of dialysis, with a high percentage of zeros,
      in the Comprehensive Dialysis Study participants. Hospitalization counts are
      modeled as a function of sparse longitudinal measurements of serum albumin
      concentrations, patient demographics, and comorbidities. Simulation studies are
      used to study finite sample properties of the proposed method and include
      comparisons with an adaptation of standard principal components regression.

PMID- 24942315
TI  - Enzymes in the dissolution testing of gelatin capsules.
AB  - Gelatin capsules are a widely used dosage form both for pharmaceutical drug
      products as well as dietary supplements. Gelatin in the presence of certain
      compounds, mainly aldehydes, or in high humidity and high temperature conditions
      can cross-link. Cross-linking involves covalent bonding of the amine group of a
      lysine side chain of one gelatin molecule to a similar amine group on another
      molecule. The covalent bonding is, for practical purposes, irreversible. Cross
      linking results in the formation of a pellicle on the internal or external
      surface of the gelatin capsule shell that prevents the capsule fill from being
      released. In vitro dissolution testing of cross-linked gelatin capsules can
      result in slower release of the drug or no release at all. The data obtained by
      the Gelatin Capsule Working Group, created in the early 90s to investigate
      noncompliance of gelatin capsules, was used to establish the type and amounts of
      enzymes that can be added to the dissolution medium in the case of test failure
      to the presence of cross-linking in the gelatin. The two-tier dissolution testing
      was included in the US Pharmacopeia and it recommends the addition of pepsin (pH
      below 6.8) or pancreatin (pH above 6.8) to the medium depending on its pH. Pepsin
      shows good protease activity up to pH 4 and pancreatin above pH 6 leaving a gap
      where neither one has good activity. Possible proteolytic enzymes that could be
      used for the pH range 4-6.8 could be papain or bromelain.

PMID- 24942316
TI  - Association of better iron status biomarkers and coronary artery disease risk.
AB  - BACKGROUND: Epidemiological evidence concerning the role of body iron in coronary
      artery disease (CAD) is inconsistent, which is largely explained by the lack of
      relatively ideal estimations of body iron stores. AIM: The aim of the present
      study was to attempt to explore the ideal iron indicator that has the best effect
      on disease risk for further studies related to iron overload metabolism research
      worldwide. METHODS: A case-control study was conducted with 258 CAD cases and 282
      healthy controls. The association of serum iron (SI) parameters, including SI,
      total iron-binding capacity (TIBC), serum ferritin (SF) and serum transferrin
      receptor (sTfR), and CAD risk, was evaluated with receiver operating
      characteristic analysis. The areas under the receiver operating characteristic
      curve (AUC) were compared with each other to indicate the one showing the
      strongest association with CAD risk. RESULTS: The AUC (95% confidence interval)
      were 0.73 (0.69-0.77), 0.74 (0.69-0.78), 0.53 (0.48-0.58) and 0.61 (0.56-0.66)
      for SI, TIBC, SF and sTfR respectively. After comparing the AUC with each other,
      the combination of SI and TIBC (AUC (95% confidence interval): 0.86 (0.83-0.90))
      was superior to other examined iron parameters or the combination of iron
      indicators (P < 0.05). CONCLUSIONS: The present study indicated that the
      combination of SI and TIBC may have the best effect on CAD risk. Further studies
      are warranted to verify this preliminary result.

PMID- 24942313
TI  - Emerging roles of aquaporins in relation to the physiology of blood-feeding
      arthropods.
AB  - Aquaporins (AQPs) are proteins that span plasma membranes allowing the movement
      of water and small solutes into or out of cells. The type, expression levels and
      activity of AQPs play a major role in the relative permeability of each cell to
      water or other solutes. Research on arthropod AQPs has expanded in the last 10
      years due to the completion of several arthropod genome projects and the
      increased availability of genetic information accessible through other resources
      such as de novo transcriptome assemblies. In particular, there has been
      significant advancement in elucidating the roles that AQPs serve in relation to
      the physiology of blood-feeding arthropods of medical importance. The focus of
      this review is upon the significance of AQPs in relation to hematophagy in
      arthropods. This will be accomplished via a narrative describing AQP functions
      during the life history of hematophagic arthropods that includes the following
      critical phases: (1) Saliva production necessary to blood feeding, (2) Intake and
      excretion of water during blood digestion, (3) Reproduction and egg development
      and (4) Off-host environmental stress tolerance. The concentration on these
      phases will highlight known vulnerabilities in the biology of hematophagic
      arthropods that could be used to develop novel control strategies as well as
      research topics that have yet to be examined. 

PMID- 24942317
TI  - Green tea extract inhibition of human leiomyoma cell proliferation is mediated
      via catechol-O-methyltransferase.
AB  - BACKGROUND/AIMS: To investigate the inhibitory effect of green tea extract,
      epigallocatechin gallate (EGCG), on wild-type human leiomyoma (WT-HuLM) cells and
      its potential action via catechol-o-methyltransferase (COMT) activity. METHODS:
      Cell proliferation of WT-HuLM and COMT gene-silenced HuLM (COMT-shRNA-HuLM) cells
      treated with 0 or 100 uM EGCG for 7 days was measured using the MTT method. Total
      RNA and protein were extracted from cells treated with 0 or 100 uM of EGCG for 48
      h. Gene expression profiling was performed using Human Signal Transduction
      PathwayFinder. Proliferation cell nuclear antigen (PCNA), cyclin-dependent kinase
      4 (Cdk4) and COMT protein levels were detected by Western blot analyses. COMT
      enzyme activity was evaluated by HPLC. RESULTS: EGCG-treated WT-HuLM cells showed
      significantly decreased COMT expression (p < 0.001) and enzyme activity (p <
      0.05) compared to untreated WT-HuLM cells, while COMT-shRNA-HuLM cells showed no
      significant change. At 100 MUM of EGCG, survival of WT-HuLM cells was
      significantly lower (p < 0.05) compared to COMT-shRNA-HuLM cells. EGCG treatment
      modulated multiple signaling pathways in WT-HuLM compared to untreated control,
      while changes were minimal or reversed in COMT-shRNA-HuLM cells. EGCG
      significantly decreased PCNA, Cdk4 and soluble COMT protein levels (p < 0.001) in
      WT-HuLM, but not in COMT-shRNA-HuLM cells. CONCLUSIONS: The antiproliferative and
      gene-modulating effects of EGCG on HuLM cells are mediated, at least partially,
      via its effect on COMT expression and enzyme activity.

PMID- 24942318
TI  - Developing a long-term condition's information service in collaboration with
      third sector organisations.
AB  - BACKGROUND: People with long-term conditions need to be signposted to high
      quality information and advice to understand and manage their condition.
      Information seeking tools combined with third sector information could help
      address their information needs. OBJECTIVE: To describe the development and
      implementation of an information service for people living with long-term
      conditions at one NHS acute trust in the Northeast of England. METHODS: An
      information service was trialled using bespoke information models for three long
      term conditions in collaboration with third sector organisations. These guided
      people to relevant, timely and reliable information. Both clinician and service
      user questionnaires were used to evaluate satisfaction with the service. RESULTS:
      Appropriately designed information models can be used interchangeably across all
      services. Between 75% and 91% of users agreed that they were satisfied with
      various aspects of the service. Generally, users received relevant,
      understandable and high quality information at the right time. Nearly all health
      professionals (94-100%) felt the service was accessible, provided high quality
      information and did not significantly impact on their consultation time.
      CONCLUSION: The developed information service was well received by service users
      and health professionals. Specifically, the use of information prescriptions and
      menus facilitated access to information for people with long-term conditions.

PMID- 24942319
TI  - Effects of carbon-ion beam irradiation on the angiogenic response in lung
      adenocarcinoma A549 cells.
AB  - Radiotherapy has been focused mainly on killing cancer cells, and little
      attention has been paid to the process supporting tumor growth and metastasis,
      including the process of angiogenesis. To investigate the effects of carbon-ion
      irradiation on angiogenesis in lung cancer cells, we examined the expression of
      vascular endothelial growth factor and basic fibroblast growth factor in the
      tumor conditioned medium (TCM) of A549 cells exposed to carbon-ion or X-ray
      irradiation, as well as endothelial cell growth, invasion, and tube formation
      induced by TCM. No changes in vascular endothelial growth factor secretion were
      detected in the TCM of A549 cells exposed to carbon-ion irradiation at 2 or 4 Gy,
      whereas 1 Gy of irradiation significantly decreased vascular endothelial growth
      factor and basic fibroblast growth factor levels. Carbon-ion irradiation at 1 Gy
      inhibited endothelial cell invasion and tube formation. The TCM from A549 cells
      irradiated with X-ray promoted angiogenesis, whereas the TCM of A549 cells
      exposed to carbon-ion irradiation at 2 or 4 Gy had no effect. These findings
      suggest that carbon-ion irradiation at 1 Gy significantly suppressed the process
      of angiogenesis in vitro by inhibiting endothelial cell invasion and tube
      formation, which are related to vascular endothelial growth factor and basic
      fibroblast growth factor production. 

PMID- 24942320
TI  - The Habsburg Jaw-re-examined.
AB  - "Habsburg Jaw" is a frequently used eponymous designation for patients with
      mandibular prognathism, hyperplasia, or overgrowth. The purpose of this study was
      to evaluate portraits of the Spanish Habsburgs to determine the relative
      contributions of maxillary deficiency and mandibular prognathism to overall
      facial appearance. Representative portraits of the Spanish Habsburgs were
      assessed by 4 investigators for the presence of 11 anatomic features of maxillary
      deficiency and 7 of mandibular prognathism. Each characteristic was given a
      binary score of 1 if present and 0 if absent. Thus, the maximum score would be 11
      for maxillary deficiency and 7 for mandibular prognathism. A semi-quantitative
      scale was established to determine the likelihood of each diagnosis: Maxillary
      deficiency: 0-4.99 (unlikely), 5-7.99 (likely), 8-11 (very likely); mandibular
      prognathism: 0-2.99 (unlikely), 3-5.99 (likely), 6-7 (very likely). Six of 7
      Habsburg rulers were considered either likely or very likely to have maxillary
      deficiency, whereas 3/7 were assessed as likely and 4 unlikely to have mandibular
      prognathism. The results of this study suggest that the primary deformity of the
      "Habsburg Jaw" is maxillary deficiency rather than absolute mandibular
      prognathism.

PMID- 24942321
TI  - The effectiveness of interventions aimed at reducing anxiety in health care
      waiting spaces: a systematic review of randomized and nonrandomized trials.
AB  - BACKGROUND: Reducing waiting anxiety is an important objective of patient
      centered care. Anxiety is linked to negative health outcomes, including longer
      recovery periods, lowered pain thresholds, and for children in particular,
      resistance to treatment, nightmares, and separation anxiety. The goals of this
      study were (1) to systematically review published research aimed at reducing
      preprocedural waiting anxiety, and (2) to provide directions for future research
      and development of strategies to manage preprocedural waiting anxiety in health
      care environments. METHODS: We performed a systematic review of the literature
      via ISI Web of Knowledge, PubMed, PsycINFO, EMBASE, CINAHL, and Medline. Included
      in this review were studies describing measurable outcomes in response to
      interventions specifically intended to improve the waiting experience of patients
      in health care settings. Primary outcomes of interest were stress and anxiety.
      Exclusion criteria included (a) studies aimed at reducing wait times and
      management of waiting lists only, (b) waiting in non-health care settings, (c)
      design of health care facilities with nonspecific strategies pertaining to
      waiting spaces, (d) strategies to reduce pain or anxiety during the course of
      medical procedures, and (e) interventions such as massage, acupuncture, or
      hypnosis that require dedicated staff and/or private waiting environments to
      administer. RESULTS: We identified 8690 studies. Forty-one articles met the
      inclusion criteria. In adult populations, 33 studies were identified, wherein the
      effects of music (n = 25), aromatherapy (n = 6), and interior design features (n
      = 2) were examined. Eight pediatric studies were identified investigating play
      opportunities (n = 2), media distractions (n = 2), combined play opportunities
      and media distractions (n = 3), and music (n = 1). Based on results from 1129
      adult participants in the 14 studies that evaluated music and permitted meta
      analysis, patients who listened to music before a medical procedure exhibited a
      lowered-state anxiety (-5.1 +/- 0.53 points on the State Trait Anxiety Scale)
      than those who received standard care. The efficacy of aromatherapy was
      inconclusive. Studies reporting on the impact of improved interior design of
      waiting areas, while positive, are minimal and heterogeneous. For children,
      insufficient evidence is available to corroborate the effectiveness of play
      opportunities, media distractions, and music for mitigating anxiety in children
      awaiting medical procedures. CONCLUSIONS: Music is a well-established means of
      decreasing anxiety in adult patients awaiting medical interventions. The effect
      of music on children's anxiety is not known. Limited studies and heterogeneity of
      interventions and methods in the areas of aromatherapy, interior design, digital
      media, and play opportunities (for children) suggest the need for future
      research.

PMID- 24942322
TI  - Management of postmenopausal osteoporosis and the prevention of fractures.
AB  - Postmenopausal osteoporosis affects millions of women, being estrogen deficiency
      the key factor in the pathogenesis of involutional osteoporosis. Fracture
      prevention is one of the public health priorities worldwide. Different treatments
      for osteoporosis are available. The various options are aimed to maintain bone
      health and decrease the risk of fractures. The majority of these drugs are
      antiresorptive agents, i.e., drugs that lower bone turnover, inhibiting
      osteoclastic bone resorption. Dietary sources of calcium intake and vitamin D are
      ideal, while pharmachological supplements should be used if diet alone cannot
      provide the recommended daily intake. Bisphosphonates are first-line therapy for
      patients with established osteoporosis at high risk of fracture. Some serious,
      but rare, adverse events have been associated with their long-term
      administration. The monoclonal antibody to RANKL, named denosumab, administered
      as a 60-mg subcutaneous injection every 6 months, is a valuable option for the
      treatment of postmenopausal osteoporosis in women at increased or high risk of
      fractures, who are unable to take other osteoporosis treatments. Teriparatide
      (PTH 1-34) is the only available osteoanabolic drugs for osteoporosis treatment
      at present. Its use is limited to severe osteoporosis because of the high cost of
      the treatment. In climacteric women, in different stages of menopausal
      transition, and beyond, hormone replacement therapy at different doses (HRT)
      rapidly normalizes turnover, preventing and/or treating osteoporosis. HRT is able
      to preserve and even increase BMD at all skeletal sites, leading to a significant
      reduction in vertebral and non-vertebral fractures. Selective estrogen modulators
      (SERMs) as raloxifene and bazedoxifene reduce bone turnover and maintains or
      increases vertebral and femoral BMDs in comparison to placebo and reduces the
      risk of vertebral and new vertebral fractures, in high risk women. The
      combination of a SERM with an estrogen has been defined as tissue selective
      estrogen complex (TSEC). The bazedoxifene with conjugated estrogen is able to
      reduce climacteric symptoms, reducing bone turnover and preserving BMD. Studies
      investigating the actions of phytoestrogens on BMD or bone turnover are largely
      contradictory, making them inconclusive. At the present time, phytoestrogens
      cannot be recommended for postmenopausal osteoporosis. In conclusion, the use of
      HRT for osteoporosis prevention is based on biology, epidemiology, animal and
      preclinical data, observational studies and randomized, clinical trials.
      Osteoporosis prevention can actually be considered as a major additional effect
      in climacteric women who use HRT for treatment of climacteric symptoms. Bone
      protection is one of the major benefits of HRT. The possibility that low dose HRT
      or TSEC causes a decrease in fracture risk is not demonstrated but the scientific
      evidence is compelling. Conversely, established osteoporosis, often occurring in
      elderly women, can better be treated with specific treatments, such as
      bisphosphonates or, in more severe and selected cases, anabolic agents
      (teriparatide). 

PMID- 24942323
TI  - Measuring job quality: a study with bus drivers.
AB  - There is growing interest in the contribution which job design can make to worker
      health; also a desire to better understand the multidimensional notion of 'job
      quality' and to develop approaches to measuring this. This paper reviews concepts
      of 'job quality' and 'good jobs' and examines these issues in the work of bus
      drivers, an occupational group commonly reported as having poor health and poor
      working conditions. The DGB-Index (Deutscher Gewerkschaftsbund Good Work Index),
      a tool used recently in Germany for measuring job quality, was translated and
      administered to a sample of UK bus drivers (n = 381). It found job quality to be
      significantly lower than that for a group of non-drivers in the same
      organisation; and better than that for a sample of German bus drivers. We
      conclude that the DGB-Index is an effective tool for measuring job quality and
      providing feedback to employers; and could be used to compare job quality between
      organisations or internationally. 

PMID- 24942324
TI  - Potential role of serotonin1A receptors in post-weaning social isolation-induced
      abnormal behaviors in rodents.
AB  - Post-weaning social isolation in mice induces behavioral abnormalities such as
      hyperactivity, aggression, depression- and anxiety-like behaviors, deficits of
      prepulse inhibition, and reduced pain sensitivity to the noxious stimuli. Then,
      this mouse is considered to be a model of psychiatric disorders including
      schizophrenia. We have found that serotonin (5-HT)(1A)-receptor ligands attenuate
      these abnormalities, suggesting the pharmacological role of the receptor in
      treatment of psychiatric disorders. Furthermore, we have recently found that
      isolation-reared mice show social encounter-induced hyperactivity, a novel
      phenotype of the abnormal behaviors, and the hyperactivity is triggered by
      activation of the serotonergic system from the dorsal raphe to the frontal
      cortex. This review summarizes the effects of 5-HT(1A) receptor ligands on
      aggressive behavior, deficits of prepulse inhibition, reduced pain sensitivity to
      the noxious stimuli, and encounter-induced hyperactivity in social isolation
      reared mice. These findings suggest that the 5-HT(1A) receptor is a potential
      target molecule for treatment of psychiatric disorders and pain.

PMID- 24942325
TI  - Vitamin D and S-farnesylthiosalicylic acid have a synergistic effect on hepatic
      stellate cells proliferation.
AB  - BACKGROUND: Hepatic stellate cells (HSCs) have a key role in the formation of
      hepatic fibrosis. The active form of vitamin D, 1,25(OH)2D3, has been found to
      have antiproliferative and antifibrotic effects in various tissues including
      liver. Farnesylthiosalicylic acid (FTS), a novel Ras antagonist, was also found
      to inhibit hepatic fibrosis. AIMS: The purpose of this study was to examine the
      antiproliferative and antifibrotic effects of the combined treatment of
      1,25(OH)2D3 and FTS on primary cultured HSCs. METHODS: Primary HSCs, isolated
      from rat's livers, were treated with 1,25(OH)2D3, FTS or a combination of both.
      Proliferation was assessed by bromodeoxyuridine. Expression of p-ERK, ERK, Ras
      GTP, total-Ras, CyclinD1 and fibrotic markers was measured by western blotting
      analysis and real-time PCR. Cytotoxicity was assessed by lactate dehydrogenase
      method. RESULTS: The combined treatment inhibited HSCs proliferation by
      threefold. The effect was synergistic and non-cytotoxic. In concordance, the
      combined treatment suppressed CyclinD1 expression by ~2-fold, whereas 1,25(OH)2D3
      or FTS alone showed a significantly lower inhibitory effect. The effect of the
      combined treatment on CyclinD1 expression was mediated via Ras-GTP and p-ERK
      signal transduction pathway. The effect on fibrotic markers showed that
      1,25(OH)2D3 decreased collagen Ialpha1 expression by ~40%, FTS by ~50% and the
      combined treatment by ~60%. 1,25(OH)2D3 inhibited tissue inhibitor of
      metalloproteinases-1 (TIMP-1) expression by 20%. FTS alone or 1,25(OH)2D3 + FTS
      inhibited TIMP-1 expression by 60%. FTS inhibited transforming growth factor-beta
      (TGF-beta) expression by 25%, while 1,25(OH)2D3 had no effect. CONCLUSION:
      Although the combination of 1,25(OH)2D3 and FTS did not demonstrate an additive
      antifibrotic effect, it showed a synergistic antiproliferative effect on primary
      HSCs. Therefore, the combined treatment may have a potential therapeutic value in
      the initiation of fibrotic process.

PMID- 24942326
TI  - Methotrexate toxicity during treatment of chronic plaque psoriasis: a case report
      and review of the literature.
AB  - Methotrexate continues to be one of the most widely used systemic
      immunosuppressive agents in dermatology. In addition to the important, well
      characterized adverse effects such as hepatotoxicity and myelosuppression,
      methotrexate may induce a number of rare cutaneous adverse events including
      methotrexate-induced ulceration. We present a case of methotrexate-induced
      cutaneous ulceration in a patient with chronic plaque psoriasis occurring during
      long-standing methotrexate therapy. Withdrawal of the drug and appropriate skin
      care led to rapid healing of the ulceration and the agent was later safely
      reintroduced for the ongoing management of the patient's chronic plaque
      psoriasis. Review of the literature demonstrates cases of this important rare
      adverse event, primarily occurring in patients with chronic plaque psoriasis,
      induced by triggers such as accidental overdose or introduction of an interacting
      agent. Cutaneous ulceration typically precedes other markers of toxicity. Active
      treatment with folinic acid (calcium leucovorin) may be required. Early
      recognition, prompt cessation of methotrexate, and appropriate treatment
      minimizes morbidity. Dermatologists need to be alert to the possibility of
      cutaneous adverse events associated with methotrexate therapy, aware of potential
      drug interactions, and confident in the management of methotrexate toxicity. 

PMID- 24942327
TI  - Life-history trade-offs mediate 'personality' variation in two colour morphs of
      the pea aphid, Acyrthosiphon pisum.
AB  - Life-history trade-offs are considered a major driving force in the emergence of
      consistent behavioural differences (personality variation); but empirical tests
      are scarce. We investigated links between a personality trait (escape response),
      life-history and state variables (growth rate, size and age at first
      reproduction, age-dependent reproductive rates, lifetime reproductive success,
      life span) in red and green colour morphs of clonal pea aphids, Acyrthosiphon
      pisum. Escape response (dropping/non-dropping off a plant upon a predatory
      attack) was measured repeatedly to classify individuals as consistent droppers,
      consistent nondroppers or inconsistents. Red morphs experienced stronger trade
      offs between early reproduction and life span than green morphs; and red
      consistent (non)droppers had highest lifetime reproductive success. Red droppers
      followed a risk-averse life-history strategy (high late reproduction), red
      nondroppers a risk-prone strategy (high early reproduction), while reproductive
      rates were equivalent for all green behavioural types and red inconsistents. This
      suggests that red morphs suffer the highest costs of dropping (they are most
      conspicuous to predators), which 'equivalates' fitness payoffs to both risk
      takers (red non-droppers) and risk-averse red droppers. The strong trade-off also
      means that committing to a particular lifestyle (being consistent) maximises
      fitness. Our study suggests that life-history trade-offs likely mediate
      personality variation but effects might depend on interactions with other
      organismal characteristics (here: colour morph). 

PMID- 24942328
TI  - Functional and biological diversity of foliar spectra in tree canopies throughout
      the Andes to Amazon region.
AB  - Spectral properties of foliage express fundamental chemical interactions of
      canopies with solar radiation. However, the degree to which leaf spectra track
      chemical traits across environmental gradients in tropical forests is unknown. We
      analyzed leaf reflectance and transmittance spectra in 2567 tropical canopy trees
      comprising 1449 species in 17 forests along a 3400-m elevation and soil fertility
      gradient from the Amazonian lowlands to the Andean treeline. We developed
      quantitative links between 21 leaf traits and 400-2500-nm spectra, and developed
      classifications of tree taxa based on spectral traits. Our results reveal
      enormous inter-specific variation in spectral and chemical traits among canopy
      trees of the western Amazon. Chemical traits mediating primary production were
      tightly linked to elevational changes in foliar spectral signatures. By contrast,
      defense compounds and rock-derived nutrients tracked foliar spectral variation
      with changing soil fertility in the lowlands. Despite the effects of abiotic
      filtering on mean foliar spectral properties of tree communities, the spectra
      were dominated by phylogeny within any given community, and spectroscopy
      accurately classified 85-93% of Amazonian tree species. Our findings quantify how
      tropical tree canopies interact with sunlight, and indicate how to measure the
      functional and biological diversity of forests with spectroscopy. 

PMID- 24942329
TI  - Developing gradient metal alloys through radial deposition additive
      manufacturing.
AB  - Interest in additive manufacturing (AM) has dramatically expanded in the last
      several years, owing to the paradigm shift that the process provides over
      conventional manufacturing. Although the vast majority of recent work in AM has
      focused on three-dimensional printing in polymers, AM techniques for fabricating
      metal alloys have been available for more than a decade. Here, laser deposition
      (LD) is used to fabricate multifunctional metal alloys that have a strategically
      graded composition to alter their mechanical and physical properties. Using the
      technique in combination with rotational deposition enables fabrication of
      compositional gradients radially from the center of a sample. A roadmap for
      developing gradient alloys is presented that uses multi-component phase diagrams
      as maps for composition selection so as to avoid unwanted phases. Practical
      applications for the new technology are demonstrated in low-coefficient of
      thermal expansion radially graded metal inserts for carbon-fiber spacecraft
      panels. 

PMID- 24942331
TI  - Reconstruction with vascularized medial femoral condyle flaps in hindfoot and
      ankle defects: a report of two cases.
AB  - In this article, we report using free vascularized medial femoral condyle (MFC)
      flaps for reconstruction of bone defects and nonunion of the hindfoot and ankle
      in two patients. One patient had an open calcaneal fracture and hindfoot bone
      defect with impaired gait due to Achilles tendon functional loss. The second
      patient had nonunion with a chondral defect of the talus after a fall. Following
      uneventful recoveries, good objective and subjective results were achieved in
      terms of pain reduction and improved gait in both patients. No further operative
      intervention was needed during a 3-year follow-up period. The versatility of the
      corticoperiosteal graft from the MFC makes it an important reconstructive tool
      for addressing several major surgical problems of bony nonunion in the
      extremities, including posttraumatic reconstruction of hindfoot and ankle
      disorders.

PMID- 24942332
TI  - Integrated molecular, interfacial, and device engineering towards high
      performance non-fullerene based organic solar cells.
AB  - High-performance non-fullerene OSCs with PCEs of up to ca. 6.0% are demonstrated
      based on PBDTT-F-TT polymer and a molecular di-PBI acceptor through comprehensive
      molecular, interfacial, and device engineering. Impressive PCEs can also be
      retained in devices with relatively thick BHJ layer and processed through non
      halogenated solvents, indicating these high-performance non-fullerene OSCs are
      promising for large-area printing applications. 

PMID- 24942330
TI  - Cytotoxic, genotoxic, and neurotoxic effects of Mg, Pb, and Fe on
      pheochromocytoma (PC-12) cells.
AB  - Metals such as lead (Pb), magnesium (Mg), and iron (Fe) are ubiquitous in the
      environment as a result of natural occurrence and anthropogenic activities.
      Although Mg, Fe, and others are considered essential elements, high level of
      exposure has been associated with severe adverse health effects including
      cardiovascular, hematological, nephrotoxic, hepatotoxic, and neurologic
      abnormalities in humans. In the present study we hypothesized that Mg, Pb, and Fe
      are cytotoxic, genotoxic and neurotoxic, and their toxicity is mediated through
      oxidative stress and alteration in protein expression. To test the hypothesis, we
      used the pheochromocytoma (PC-12) cell line as a neuro cell model and performed
      the LDH assay for cell viability, Comet assay for DNA damage, Western blot for
      oxidative stress, and HPLC-MS to assess the concentration levels of neurological
      biomarkers such as glutamate, dopamine (DA), and 3-methoxytyramine (3-MT). The
      results of this study clearly show that Mg, Pb, and Fe, respectively in the form
      of MgSO4 , Pb(NO3 )2 , FeCl2 , and FeCl3 induce cytotoxicity, oxidative stress,
      and genotoxicity in PC-12 cells. In addition, exposure to these metallic
      compounds caused significant changes in the concentration levels of glutamate,
      dopamine, and 3-MT in PC-12 cells. Taken together the findings suggest that MgSO4
      , Pb(NO3 )2 , FeCl2 , and FeCl3 have the potential to induce substantial toxicity
      to PC-12 cells.

PMID- 24942336
TI  - Primary squamous cell of the thyroid-an abbreviated clinical presentation.
AB  - BACKGROUND: Lacking any squamous epithelium, thyroid gland with primary squamous
      cell carcinoma (PSCC) proves to be an etiopathophysiological quandary. Two major
      theories do exist, though few cases have been documented to support either. We
      present a case that supports the "metaplasia" theory, which serves to enhance our
      understanding of a disease that carries with it a very poor prognosis. CASE
      PRESENTATION: We present a case of an extremely advanced, primary squamous cell
      carcinoma of the thyroid with distant metastases in a thirty-six year-old male.
      Dying of airway compromise seventeen days following his admission, this is the
      shortest median survival of all documented cases. CONCLUSION: In addition to
      being the most abbreviated time period between presentation and death of all
      documented thyroid primary squamous cell carcinomas, we share the fifth case of
      thyroid PSCC in the setting of lymphocytic thyroiditis. This case should build
      awareness of the aggressivity of the disease and the lack of established
      diagnostic criteria.

PMID- 24942335
TI  - Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment
      of patients with newly diagnosed/untreated multiple myeloma.
AB  - INTRODUCTION: Bortezomib is a proteasome inhibitor that has shown important
      clinical efficacy either as a single agent or in combination in patients with
      multiple myeloma (MM). In the present protocol, bortezomib was combined with
      bendamustine and prednisone, in order to assess the efficacy and safety of this
      combination therapy in patients with newly diagnosed/untreated MM. METHODS:
      Between June 2006 and October 2013, 49 patients with newly diagnosed/untreated MM
      were treated with bendamustine 60 mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2)
      on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11
      bendamustine, prednisone and bortezomib (BPV) once every 21 days. Patients were
      divided into three groups: group A (n = 19) consisted of patients with normal
      renal function or mild dysfunction (eGFR >= 60 ml/min), group B (n = 15) patients
      with moderate or severe renal dysfunction (eGFR 15-59 ml/min) and group C (n =
      15) patients with renal failure/dialysis (eGFR <15 ml/min). RESULTS: A median
      number of two (range 1-5) BPV treatment cycles were given to the patients. The
      majority of the patients (n = 40, 82 %) responded after at least one cycle of BPV
      therapy with five stringent complete responses (CRs), nine near complete
      responses, 12 very good partial responses and 14 partial responses. Five patients
      had MR, three stable and one progressive disease. After a median observation time
      of 13 months, progression-free survival (PFS) and overall survival (OS) at 12
      months were 92 and 94 %, respectively, for patients with normal renal function or
      mild renal dysfunction (group A) and 83 and 93 %, respectively, for patients with
      moderate or severe renal dysfunction (group B). Outcome for these patients was
      slightly better but not statistically significantly better than that for patients
      with renal failure/dialysis (group C), who had a PFS, and OS of 66 % (p = 0.08)
      and 73 % (p = 0.05), respectively. These results indicate that this BPV
      combination is feasible, effective and well tolerated in patients with newly
      diagnosed MM and normal or impaired renal function.

PMID- 24942334
TI  - The BRAF mutation is associated with the prognosis in colorectal cancer.
AB  - BACKGROUND: Two members of the Ras/Raf signaling pathway, KRAS and B-raf, are
      suspected to be involved in the stepwise progression of colorectal cancer (CRC)
      tumorigenesis. OBJECTIVE: We compared the KRAS and BRAF mutation status of CRC
      patients with their clinicopathological characteristics and examined the effect
      of mutation status on survival rates. METHODS: DNA was extracted from 164
      samples, and the mutation statuses of KRAS and BRAF were assessed using peptide
      PNA clamp real-time PCR method. The presences of mutation were compared with
      clinicopathological factors and 5-year survival rate. RESULTS: Among the 164 CRC
      cases, KRAS mutation as detected in 71 cases (43.3 %), respectively, with no
      relationship with clinicopathological factors of the patients. On Kaplan-Meier
      survival analysis, KRAS mutation was not significantly associated with survival
      (p = 0.971). BRAF mutation was detected in 26 cases (15.9 %) and not associated
      with clinicopathological factors of the patients. However, the 5-year survival
      rate of BRAF mutations was significantly decreased (p = 0.02). CONCLUSIONS: The
      presence of KRAS mutation did not correlate with the various clinicopathological
      factors of CRC patients or the survival rate. However, the survival rate was
      reduced in BRAF-mutated CRC patients. Therefore, BRAF mutation could be an
      important prognostic factor in CRC patients.

PMID- 24942337
TI  - Atmospheric vs. anaerobic processing of metabolome samples for the metabolite
      profiling of a strict anaerobic bacterium, Clostridium acetobutylicum.
AB  - Well-established metabolome sample preparation is a prerequisite for reliable
      metabolomic data. For metabolome sampling of a Gram-positive strict anaerobe,
      Clostridium acetobutylicum, fast filtration and metabolite extraction with
      acetonitrile/methanol/water (2:2:1, v/v) at -20 degrees C under anaerobic
      conditions has been commonly used. This anaerobic metabolite processing method is
      laborious and time-consuming since it is conducted in an anaerobic chamber. Also,
      there have not been any systematic method evaluation and development of
      metabolome sample preparation for strict anaerobes and Gram-positive bacteria. In
      this study, metabolome sampling and extraction methods were rigorously evaluated
      and optimized for C. acetobutylicum by using gas chromatography/time-of-flight
      mass spectrometry-based metabolomics, in which a total of 116 metabolites were
      identified. When comparing the atmospheric (i.e., in air) and anaerobic (i.e., in
      an anaerobic chamber) processing of metabolome sample preparation, there was no
      significant difference in the quality and quantity of the metabolomic data. For
      metabolite extraction, pure methanol at -20 degrees C was a better solvent than
      acetonitrile/methanol/water (2:2:1, v/v/v) at -20 degrees C that is frequently
      used for C. acetobutylicum, and metabolite profiles were significantly different
      depending on extraction solvents. This is the first evaluation of metabolite
      sample preparation under aerobic processing conditions for an anaerobe. This
      method could be applied conveniently, efficiently, and reliably to metabolome
      analysis for strict anaerobes in air.

PMID- 24942333
TI  - Incidence rates of carbapenemase-producing Enterobacteriaceae clinical isolates
      in France: a prospective nationwide study in 2011-12.
AB  - OBJECTIVES: To determine proportions and incidence rates of Enterobacteriaceae
      producing carbapenemase among those non-susceptible (NS) to carbapenems in
      France. METHODS: From November 2011 to April 2012, 71 laboratories recorded non
      duplicate Enterobacteriaceae clinical isolates NS to at least one carbapenem and
      the total number of isolates of the different species. Carbapenem MICs were
      determined by broth microdilution and the beta-lactamase content by DNA
      microarray. RESULTS: During the study period, the 71 laboratories identified 133
      244 Enterobacteriaceae isolates, of which 846 (0.63%) were NS to at least one
      carbapenem. Carbapenem-NS isolates accounted for 0.07% (61/90 148) among
      Escherichia coli isolates, 1.1% (111/10 436) among Klebsiella pneumoniae, 8.2%
      (492/5971) among Enterobacter cloacae and 4.0% (84/2104) among Enterobacter
      aerogenes. Among the 541 available carbapenem-NS isolates, 222 (including 63
      randomly selected E. cloacae) were further analysed after confirmation of
      carbapenem non-susceptibility. None of the Enterobacter spp. isolates produced
      carbapenemase. Among the other species, 28 isolates produced carbapenemases (22
      OXA-48, 4 KPC and 2 NDM), accounting for an estimated proportion of carbapenemase
      producing isolates of 0.08% for all species, 0.01% for E. coli and 0.27% for K.
      pneumoniae. The incidence-density rate in the participating hospitals was 0.0041
      per 1000 hospital-days and the incidence rate was 0.0027 per 100 admissions.
      CONCLUSIONS: The incidence-density rate of carbapenemase-producing isolates per
      1000 hospital-days was low and 30-fold lower than that of carbapenem-NS isolates
      (0.125) and almost 300-fold lower than that of ESBL-producing isolates (1.104) in
      these French hospitals.

PMID- 24942339
TI  - Trained or professional doulas in the support and care of pregnant and birthing
      women: a critical integrative review.
AB  - The professionalisation of doula care and research interest in this area of
      maternity care/support have both grown internationally in recent years
      highlighting important broader issues around the access, continuity and delivery
      of maternity care services. However, no work to date has provided a critical
      appraisal of the international literature on this topic. In response, this paper
      presents the first critical review of international empirical literature
      examining professional doula care for pregnant and birthing women. A database
      search of AMED, CINAHL, Maternity and Infant Care, and MEDLINE using the search
      term, "doula" was undertaken. A total of 48 papers published between 1980 and
      March 2013 involving trained or professional doulas were extracted. Four
      descriptive categories were identified from the review: 'workforce and
      professional issues in doula care'; 'trained or professional doula's role and
      skill'; 'physical outcomes of trained or professional doula care'; and 'social
      outcomes of trained or professional doula care'. Of the studies evaluating
      outcomes of doula care, there were a number with design and methodology
      weaknesses. The review highlights a number of gaps in the research literature
      including a lack of research examining doula workforce issues; focus upon the
      experience and perspective of significant stakeholders such as expectant fathers
      with regard to trained or professional doula care; clinical trials measuring both
      subjective experiences and physical outcomes of trained or professional doula
      support; synergy between the design of clinical trials research examining trained
      or professional doula care and the clinical reality of professional doula
      practice. It is imperative that key aspects of trained doula care be subject to
      further rigorous, empirical investigation to help establish an evidence base to
      guide policy and practice relating to this area of support and care for pregnant
      and birthing women.

PMID- 24942340
TI  - What interventions facilitate client progress through the assimilation model? A
      task analysis of interventions in the psychodynamic treatment of depression.
AB  - A variation of task analysis was used to build an empirical model of how
      therapists may facilitate client assimilation process, described in the
      Assimilation of Problematic Experiences Scale. A rational model was specified and
      considered in light of an analysis of therapist in-session performances (N = 117)
      drawn from six inpatient therapies for depression. The therapist interventions
      were measured by the Comprehensive Psychotherapeutic Interventions Rating Scale.
      Consistent with the rational model, confronting interventions were particularly
      useful in helping clients elaborate insight. However, rather than there being a
      small number of progress-related interventions at lower levels of assimilation,
      therapists' use of interventions was broader than hypothesized and drew from a
      wide range of therapeutic approaches. Concerning the higher levels of
      assimilation, there was insufficient data to allow an analysis of the therapist's
      progress-related interventions. 

PMID- 24942341
TI  - Major degradable polycations as carriers for DNA and siRNA.
AB  - Non-viral gene delivery systems are one of the most potential alternatives to
      viral vectors because of their less immunogenicity, less toxicity and easy
      productivity in spite of their low capacity of gene transfection using DNA or
      silencing using siRNA compared to that of viral vectors. Among non-viral systems,
      the polycationic derivatives are the most popular gene carriers since they can
      effectively condense nucleic acids to transfer into the cells, especially the
      polyethylenimine (PEI) which has been used as a golden standard polymer owing to
      its high buffering ability for endosomal escape of gene to be expressed. However,
      PEI has severe problems for its toxicity due to the high positive charge density
      and non-degradability although the toxicity of PEI depends on its molecular
      weight (MW) and structure. Therefore, a considerable attention has been paid on
      synthesis of degradable PEI derivatives using low MW one because low MW PEI is
      much less toxic than high MW PEI. Other degradable polycationic gene carriers
      such as polyamidoamines (PAA) and cyclodextrin (CD)-based polycations are also in
      a significant interest because of their high transfection efficiency with low
      toxicity. This review in detail explains the recent developments on these three
      major degradable polycations as promising carriers for deoxyribonucleic acid
      (DNA) and small interfering RNA (siRNA).

PMID- 24942342
TI  - Theoretical frameworks used to discuss ethical issues in private physiotherapy
      practice and proposal of a new ethical tool.
AB  - In the past, several researchers in the field of physiotherapy have asserted that
      physiotherapy clinicians rarely use ethical knowledge to solve ethical issues
      raised by their practice. Does this assertion still hold true? Do the theoretical
      frameworks used by researchers and clinicians allow them to analyze thoroughly
      the ethical issues they encounter in their everyday practice? In our quest for
      answers, we conducted a literature review and analyzed the ethical theoretical
      frameworks used by physiotherapy researchers and clinicians to discuss the
      ethical issues raised by private physiotherapy practice. Our final analysis
      corpus consisted of thirty-nine texts. Our main finding is that researchers and
      clinicians in physiotherapy rarely use ethical knowledge to analyze the ethical
      issues raised in their practice and that gaps exist in the theoretical frameworks
      currently used to analyze these issues. Consequently, we developed, for ethical
      analysis, a four-part prism which we have called the Quadripartite Ethical Tool
      (QET). This tool can be incorporated into existing theoretical frameworks to
      enable professionals to integrate ethical knowledge into their ethical analyses.
      The innovative particularity of the QET is that it encompasses three ethical
      theories (utilitarism, deontologism, and virtue ethics) and axiological ontology
      (professional values) and also draws on both deductive and inductive approaches.
      It is our hope that this new tool will help researchers and clinicians integrate
      ethical knowledge into their analysis of ethical issues and contribute to
      fostering ethical analyses that are grounded in relevant philosophical and
      axiological foundations.

PMID- 24942338
TI  - The genome of the white-rot fungus Pycnoporus cinnabarinus: a basidiomycete model
      with a versatile arsenal for lignocellulosic biomass breakdown.
AB  - BACKGROUND: Saprophytic filamentous fungi are ubiquitous micro-organisms that
      play an essential role in photosynthetic carbon recycling. The wood-decayer
      Pycnoporus cinnabarinus is a model fungus for the study of plant cell wall
      decomposition and is used for a number of applications in green and white
      biotechnology. RESULTS: The 33.6 megabase genome of P. cinnabarinus was sequenced
      and assembled, and the 10,442 predicted genes were functionally annotated using a
      phylogenomic procedure. In-depth analyses were carried out for the numerous
      enzyme families involved in lignocellulosic biomass breakdown, for protein
      secretion and glycosylation pathways, and for mating type. The P. cinnabarinus
      genome sequence revealed a consistent repertoire of genes shared with wood
      decaying basidiomycetes. P. cinnabarinus is thus fully equipped with the
      classical families involved in cellulose and hemicellulose degradation, whereas
      its pectinolytic repertoire appears relatively limited. In addition, P.
      cinnabarinus possesses a complete versatile enzymatic arsenal for lignin
      breakdown. We identified several genes encoding members of the three ligninolytic
      peroxidase types, namely lignin peroxidase, manganese peroxidase and versatile
      peroxidase. Comparative genome analyses were performed in fungi displaying
      different nutritional strategies (white-rot and brown-rot modes of decay). P.
      cinnabarinus presents a typical distribution of all the specific families found
      in the white-rot life style. Growth profiling of P. cinnabarinus was performed on
      35 carbon sources including simple and complex substrates to study substrate
      utilization and preferences. P. cinnabarinus grew faster on crude plant
      substrates than on pure, mono- or polysaccharide substrates. Finally, proteomic
      analyses were conducted from liquid and solid-state fermentation to analyze the
      composition of the secretomes corresponding to growth on different substrates.
      The distribution of lignocellulolytic enzymes in the secretomes was strongly
      dependent on growth conditions, especially for lytic polysaccharide mono
      oxygenases. CONCLUSIONS: With its available genome sequence, P. cinnabarinus is
      now an outstanding model system for the study of the enzyme machinery involved in
      the degradation or transformation of lignocellulosic biomass.

PMID- 24942345
TI  - A complex of poly(4-vinylpyridine) and tolane based hemi-phasmid benzoic acid:
      towards luminescent supramolecular side-chain liquid crystalline polymers.
AB  - A supramolecular side-chain liquid crystalline (LC) polymer P4VP(1)x was prepared
      using poly(4-vinylpyridine) and a tolane based hemi-phasmid benzoic acid.
      P4VP(1)x exhibits good processability, forming smectic and hexagonal columnar LC
      phases at different compositions. Its photoluminescence properties depend on the
      LC structures.

PMID- 24942344
TI  - Colouterine fistula after polymyomectomy: a case report.
AB  - INTRODUCTION: Colouterine fistula is a very rare condition; most cases described
      in the literature are secondary to complications of diverticulitis in elderly
      patients. CASE PRESENTATION: We report the case of a 34-year-old African woman
      who presented with a colouterine fistula secondary to polymyomectomy, which was
      diagnosed in the setting of severe endometritis. She had a Hartmann procedure and
      abundant irrigation of her abdominal and uterine cavities followed by placement
      of a double drainage in order to preserve fertility. This is the first case of a
      conservative management of the uterus in such conditions. CONCLUSION:
      Conservative surgery in colouterine fistula should be discussed as an alternative
      to hysterectomy in young infertile women.

PMID- 24942343
TI  - Biofilm-specific extracellular matrix proteins of nontypeable Haemophilus
      influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHi), a human respiratory tract pathogen,
      can form colony biofilms in vitro. Bacterial cells and the amorphous
      extracellular matrix (ECM) constituting the biofilm can be separated using
      sonication. The ECM from 24- and 96-h NTHi biofilms contained polysaccharides and
      proteinaceous components as detected by nuclear magnetic resonance (NMR) and
      Fourier transform infrared spectroscopy (FTIR) spectroscopy. More conventional
      chemical assays on the biofilm ECM confirmed the presence of these components and
      also DNA. Proteomics revealed eighteen proteins present in biofilm ECM that were
      not detected in planktonic bacteria. One ECM protein was unique to 24-h biofilms,
      two were found only in 96-h biofilms, and fifteen were present in the ECM of both
      24- and 96-h NTHi biofilms. All proteins identified were either associated with
      bacterial membranes or cytoplasmic proteins. Immunocytochemistry showed two of
      the identified proteins, a DNA-directed RNA polymerase and the outer membrane
      protein OMP P2, associated with bacteria and biofilm ECM. Identification of
      biofilm-specific proteins present in immature biofilms is an important step in
      understanding the in vitro process of NTHi biofilm formation. The presence of a
      cytoplasmic protein and a membrane protein in the biofilm ECM of immature NTHi
      biofilms suggests that bacterial cell lysis may be a feature of early biofilm
      formation. 

PMID- 24942346
TI  - Seafood consumption and umbilical cord blood mercury concentrations in a
      multiethnic maternal and child health cohort.
AB  - BACKGROUND: Fish consumption is common among the cultures of Hawaii, and given
      public health attention to mercury exposure in pregnancy, it is important to
      better understand patterns of fish consumption and mercury in pregnancy. This
      study examined the influence of maternal fish consumption during pregnancy on
      umbilical cord mercury (Hg) concentrations in a multiethnic cohort of women in
      Hawaii. METHODS: This secondary analysis of a prospective cohort pilot study
      examined antenatal seafood consumption and neonatal outcomes in Hawaii. The first
      100 eligible women who consented were enrolled. After delivery, umbilical cord
      blood and a dietary survey were obtained. RESULTS: Most women (86%) consumed
      seafood during the month prior to delivery. Overall, 9% of women consumed more
      than the recommended limit of 12 ounces/week. Seafood consumption varied
      significantly by ethnicity and income, with 30% of poor women consuming more than
      the recommended limit. Seafood consumption did not vary by age or
      education.Umbilical cord blood Hg levels were 5 MUg/L or more in 44% of women.
      Filipina were significantly less likely to have elevated Hg levels compared with
      non- Filipina (p < .05). Mercury levels did not vary by other demographic
      characteristics.Women reporting consumption exceeding 12 ounces fish per week
      were significantly more likely to have cord blood Hg levels of 5 MUg/L or more,
      but mean Hg concentrations were not significantly higher (6.1 +/- 3.3 v 5.0 +/-
      3.7). The odds ratio for elevated Hg, however, was significant among seafood
      consumers compared with non-consumers (5.7; 95% confidence interval: 1.2, 27.1).
      CONCLUSIONS: Despite Environmental Protection Agency (EPA) guidelines, a
      significant portion of pregnant women consumed more than the recommended amount
      of seafood, which was associated with race and income. Further, almost half of
      study participants had cord blood Hg concentrations at or exceeding 5 MUg/L.

PMID- 24942347
TI  - Normalization of white matter intensity on T1-weighted images of patients with
      acquired central nervous system demyelination.
AB  - BACKGROUND: Intensity variation between magnetic resonance images (MRI) hinders
      comparison of tissue intensity distributions in multicenter MRI studies of brain
      diseases. The available intensity normalization techniques generally work well in
      healthy subjects but not in the presence of pathologies that affect tissue
      intensity. One such disease is multiple sclerosis (MS), which is associated with
      lesions that prominently affect white matter (WM). OBJECTIVE: To develop a T1
      weighted (T1w) image intensity normalization method that is independent of WM
      intensity, and to quantitatively evaluate its performance. METHODS AND SUBJECTS:
      We calculated median intensity of grey matter and intraconal orbital fat on T1w
      images. Using these two reference tissue intensities we calculated a linear
      normalization function and applied this to the T1w images to produce normalized
      T1w (NT1) images. We assessed performance of our normalization method for
      interscanner, interprotocol, and longitudinal normalization variability, and
      calculated the utility of the normalization method for lesion analyses in
      clinical trials. RESULTS: Statistical modeling showed marked decreases in T1w
      intensity differences after normalization (P < .0001). CONCLUSIONS: We developed
      a WM-independent T1w MRI normalization method and tested its performance. This
      method is suitable for longitudinal multicenter clinical studies for the
      assessment of the recovery or progression of disease affecting WM.

PMID- 24942348
TI  - Binding of amphiphilic and triphilic block copolymers to lipid model membranes:
      the role of perfluorinated moieties.
AB  - A novel class of symmetric amphi- and triphilic (hydrophilic, lipophilic,
      fluorophilic) block copolymers has been investigated with respect to their
      interactions with lipid membranes. The amphiphilic triblock copolymer has the
      structure PGMA(20)-PPO(34)-PGMA(20) (GP) and it becomes triphilic after attaching
      perfluoroalkyl moieties (F9) to either end which leads to F(9)-PGMA(20)-PPO(34)
      PGMA(20)-F(9) (F-GP). The hydrophobic poly(propylene oxide) (PPO) block is
      sufficiently long to span a lipid bilayer. The poly(glycerol monomethacrylate)
      (PGMA) blocks have a high propensity for hydrogen bonding. The hydrophobic and
      lipophobic perfluoroalkyl moieties have the tendency to phase segregate in
      aqueous as well as in hydrocarbon environments. We performed differential
      scanning calorimetry (DSC) measurements on polymer bound lipid vesicles under
      systematic variation of the bilayer thickness, the nature of the lipid headgroup,
      and the polymer concentration. The vesicles were composed of phosphatidylcholines
      (DMPC, DPPC, DAPC, DSPC) or phosphatidylethanolamines (DMPE, DPPE, POPE). We
      showed that GP as well as F-GP binding have membrane stabilizing and
      destabilizing components. PPO and F9 blocks insert into the hydrophobic part of
      the membrane concomitantly with PGMA block adsorption to the lipid headgroup
      layer. The F9 chains act as additional membrane anchors. The insertion of the PPO
      blocks of both GP and F-GP could be proven by 2D-NOESY NMR spectroscopy. By
      fluorescence microscopy we show that F-GP binding increases the porosity of POPC
      giant unilamellar vesicles (GUVs), allowing the influx of water soluble dyes as
      well as the translocation of the complete triphilic polymer and its accumulation
      at the GUV surface. These results open a new route for the rational design of
      membrane systems with specific properties.

PMID- 24942349
TI  - Interprofessional collaboration at transition of care: perspectives of child and
      family health nurses and midwives.
AB  - AIMS AND OBJECTIVES: To examine collaboration in the provision of universal
      health services for children and families in Australia from the perspective of
      midwives and child health and family health nurses. BACKGROUND: Collaboration is
      identified as a key concept contributing to families' smooth transition between
      maternity and child health services. However, evidence suggests that
      collaboration between services is often lacking. Few studies have explored how
      maternity and child health and family health services or professionals
      collaborate to facilitate a smooth transition. DESIGN: This study reports on data
      collected in phases 1 and 2 of a three-phase mixed-methods study investigating
      the feasibility of implementing a national approach to child health and family
      health services in Australia (Child Health: Researching Universal Services
      study). METHODS: In phase 1, consultations (via discussion groups, focus groups
      and teleconferences) were held with 45 midwives and 60 child health and family
      health nurses. Themes identified were used to develop phase 2 surveys. In phase
      2, 1098 child health and family health nurses and 655 midwives returned surveys.
      RESULTS: Midwives and child health and family health nurses reported 'some
      collaboration'. Midwives and child health and family health nurses indicated that
      collaboration was supported by having agreement on common goals and recognising
      and valuing the contributions of others. Organisational barriers such as poor
      communication and information transfer processes obstructed relationships. Good
      collaboration was reported more frequently when working with other professionals
      (such as allied health professionals) to support families with complex needs.
      CONCLUSION: This study provides information on the nature and extent of
      collaboration from the perspective of midwives and child health and family health
      nurses providing universal health services for children and families. RELEVANCE
      TO CLINICAL PRACTICE: Both professional groups emphasised the impact of service
      disconnection on families. However, their ability to negotiate professional
      differences is affected by system constraints and differing perspectives of what
      constitutes collaboration. Developing the capacity to collaborate is essential to
      ensure smooth transition of care given ongoing changes to the system.

PMID- 24942350
TI  - Probe Dependent Solvation Dynamics Study in a Microscopically Immiscible Dimethyl
      Sulfoxide-Glycerol Binary Solvent.
AB  - Excited state dipole solvation of three coumarin dyes with different
      hydrophobicities was studied in DMSO-glycerol binary solvent. The solvation times
      obtained from the three dyes are remarkably different. The highly hydrophilic dye
      coumarin 343 (C343) exhibits the slowest solvation time (>12 ns) among all the
      dyes we used. This is in contrast to the most hydrophobic dye coumarin 153
      (C153), where the solvated state is reached just within ~104 ps. However, the
      moderately hydrophobic dye coumarin 480 (C480) demonstrates an intermediate (~396
      ps) solvation time. Unprecedented slowdown of solvation time of C343 is probably
      due to the slow diffusion of solvent molecules in the glycerol-rich first
      solvation shell followed by hydrogen bond rearrangements around the solute
      dipole. On the other hand, fast solvation of hydrophobic dye C153 is most likely
      caused by the fast reorganization dynamics of hydrophobic -CH3 groups of DMSO or
      the carbon backbone of the glycerol molecule around the solute dipole.
      Interestingly, a remarkable probe dependency in solvation dynamics was not
      observed in the case of DMSO-water binary solvent or in a neat solvent
      isopropanol. Probe dependent solvation in a DMSO-glycerol mixture is attributed
      to the microscopic phase segregation and different locations of coumarin dyes
      within this binary solvent.

PMID- 24942351
TI  - In-situ administration of dendritic cells following argon-helium cryosurgery
      enhances specific antiglioma immunity in mice.
AB  - Dendritic cells (DCs) are highly specialized antigen-presenting cells that play a
      key role in the activation of naive T cells. With an aim to explore whether in
      situ administration of DCs following argon-helium cryosurgery could enhance
      specific antiglioma immunity in mice, we evaluated the validity of this approach
      in a murine subcutaneous GL261 glioma model. C57BL/6 mice models bearing
      subcutaneous GL261 glioma were established and then divided into four groups,
      namely, no-treatment group (n=14), DC group (n=14), cryosurgery group (n=15), and
      cryosurgery+DC group (n=15). Compared with the other groups, cryosurgery combined
      with DCs injection reduced tumor sizes and significantly prolonged survival. In
      addition, the combined treatment resulted in significantly increasing percentages
      of CD3, CD3CD4 cells, the ratio of CD3CD4/CD3CD8, and the level of serum
      interleukin-12 10 days after treatments. Furthermore, in the combined treatment
      group, Th1 cells were significantly higher than those in the other groups, and
      the splenic cytotoxic T lymphocyte of mice showed significantly increasing
      specific cytotoxicity against GL261 cells. These results indicated that in
      addition to the destruction of tumor, cryosurgery combined with DCs injection
      enhanced systemic antitumor immunity, suggesting the potential usefulness of the
      combined treatment in the clinical management of gliomas. 

PMID- 24942352
TI  - How much can chest radiography contribute to the diagnosis of pulmonary emboli?

PMID- 24942353
TI  - TLR9: an important molecule in the fight against hepatitis B virus.
AB  - Hepatitis B virus (HBV) is the most prevalent infectious agent that can induce
      severe liver disease. Patients infected with long-term HBV, including chronic,
      asymptomatic and occult forms, cannot clear HBV from infected hepatocytes
      completely. It is not clear why some people can clear the infection while others
      cannot. Furthermore, the main mechanisms responsible for progression of the
      infections are not fully understood. It has been hypothesised that differences in
      genetic and immunological parameters between patients and subjects who
      successfully clear HBV infections are responsible for inducing the long-term
      forms of the infection. Previous investigations showed that Toll-like receptors
      (TLRs) play important roles in immune responses, especially innate immunity,
      against viral infections, including hepatitis B. TLR9 detects intracellular viral
      dsDNA, which results in the activation of an immune response against HBV.
      However, defects in this system may result in an attenuated response ultimately
      leading to long-term HBV infections. Targeting the defects in TLR9 or
      reactivating the downstream pathways that are normally switched on by TLR9 in
      response to HBV infection is a new approach to the treatment of long-term HBV
      infection. However, the pathways and defects seen in patients with long-term HBV
      need to be thoroughly explored before therapeutics can be applied in the clinical
      setting. Furthermore, the apparently multigenic nature of long-term HBV infection
      suggests that treatment of patients may need to be personalised. 

PMID- 24942354
TI  - Is hypertension associated with job strain? A meta-analysis of observational
      studies.
AB  - Job strain results from a combination of high workload and few decision-making
      opportunities in the workplace. There is inconsistent evidence regarding the
      association between job strain and hypertension, and methodological shortcomings
      preclude firm conclusions. Thus, a meta-analysis of observational studies on
      hypertension among occupational groups was conducted to determine whether job
      strain was associated with hypertension. In January 2012, we carried out a
      comprehensive, topic-specific electronic literature search of the Ovid MEDLINE,
      EMBASE and PsychoINFO databases complemented by individual help from non
      communicable disease experts. Experimental/interventional studies and studies on
      personality disorders were excluded. Nine of 894 identified studies met the
      eligibility criteria and were included in the meta-analysis. The pooled OR of the
      nine studies was 1.3 (95% CI 1.14 to 1.48; p<0.001), of case-control studies 3.17
      (95% CI 1.79 to 5.60; p<0.001) and of cohort studies 1.24 (95% CI 1.09 to 1.41;
      p<0.001), all of which indicated statistically significant positive associations
      between job strain and hypertension. In a subgroup analysis, cohort studies of
      good methodological quality showed significant associations between job strain
      and hypertension, while those of poor methodological quality showed no
      association or subgroup differences. We conclude that despite methodological
      differences, case-control and cohort studies of good methodological quality
      showed positive associations between hypertension and job strain. 

PMID- 24942356
TI  - Drug-induced gastrointestinal disorders.
AB  - Drug-induced gastrointestinal disorders can mimic conditions, such as
      inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and, hence,
      recognition can prevent unnecessary investigations and treatment. While the
      knowledge and awareness relating to the adverse gastrointestinal effects of some
      medications, such as non-steroidal anti-inflammatory drugs are well established,
      other commonly prescribed drugs, such as antipsychotics, antidepressants and
      metformin are less well understood and warrant further study. This review
      attempts to integrate recent information regarding adverse drug reactions and
      place this in a useful clinical context. 

PMID- 24942357
TI  - Do diseases really exist?

PMID- 24942358
TI  - Topical formulations containing finasteride. Part I: in vitro
      permeation/penetration study and in vivo pharmacokinetics in hairless rat.
AB  - In hair follicle (Hf) cells, the type-2 5-alpha-reductase enzyme, implicated in
      androgenetic alopecia, is selectively inhibited by finasteride (FNS). Because an
      effective topical formulation to deliver FNS to Hf is currently unavailable, this
      investigation aimed at evaluating in vitro FNS skin permeation and retention
      through and into hairless rat and human abdominal skin. Four hydroxypropyl
      chitosan (HPCH)-based formulations (P-08-012, P-08-016, P-08-063, and P-08-064)
      and one anhydrous formulation without HPCH (P-10-008) were tested. The
      pharmacokinetics in plasma and skin after application of P-08-016 or P-10-008 on
      dorsal rat skin with single and repeated doses was investigated. P-08-016
      performed the best in driving FNS to the reticular dermis without producing a
      high transdermal flux. Neither the in vivo single nor the repeated dose
      experiments produced plasma levels of FNS and no differences were found between
      formulations concerning skin retention. No increase in the amount of drug
      retained in the skin was obtained with the repeated dose experiment. In
      conclusion, the HPCH-based formulation P-08-016 might represent an alternative to
      systemic therapy for its ability to promote a cutaneous depot of FNS in the
      region of hair bulbs, minimizing systemic absorption even after repeated
      treatments.

PMID- 24942359
TI  - Hibernating mammals pass the acid test: multiple independent evolutions of
      enhanced proton block of sodium channels in acid-sensing pain receptors.

PMID- 24942360
TI  - The impact of training and working conditions on junior doctors' intention to
      leave clinical practice.
AB  - BACKGROUND: The shortage of physicians is an evolving problem throughout the
      world. In this study we aimed to identify to what extent junior doctors' training
      and working conditions determine their intention to leave clinical practice after
      residency training. METHODS: A prospective cohort study was conducted in 557
      junior doctors undergoing residency training in German hospitals. Self-reported
      specialty training conditions, working conditions and intention to leave clinical
      practice were measured over three time points. Scales covering training
      conditions were assessed by structured residency training, professional support,
      and dealing with lack of knowledge; working conditions were evaluated by work
      overload, job autonomy and social support, based on the Demand-Control-Support
      model. Multivariate ordinal logistic regression analyses with random intercept
      for longitudinal data were applied to determine the odds ratio of having a higher
      level of intention to leave clinical practice. RESULTS: In the models that
      considered training and working conditions separately to predict intention to
      leave clinical practice we found significant baseline effects and change effects.
      After modelling training and working conditions simultaneously, we found evidence
      that the change effect of job autonomy (OR 0.77, p = .005) was associated with
      intention to leave clinical practice, whereas for the training conditions, only
      the baseline effects of structured residency training (OR 0.74, p = .017) and
      dealing with lack of knowledge (OR 0.74, p = .026) predicted intention to leave
      clinical practice. CONCLUSIONS: Junior doctors undergoing specialty training
      experience high workload in hospital practice and intense requirements in terms
      of specialty training. Our study indicates that simultaneously improving working
      conditions over time and establishing a high standard of specialty training
      conditions may prevent junior doctors from considering leaving clinical practice
      after residency training.

PMID- 24942361
TI  - Social contexts of remission from DSM-5 alcohol use disorder in a high-risk
      sample.
AB  - BACKGROUND: Measures of social context, such as marriage and religious
      participation, are associated with remission from alcohol use disorders (AUDs) in
      population-based and treatment samples, but whether these associations hold among
      individuals at high familial risk for AUD is unknown. This study tests
      associations of measures of social context and treatment with different types of
      remission from DSM-5 AUD in a high-risk sample. METHODS: Subjects were 686
      relatives of probands (85.7% first-degree) who participated in a high-risk family
      study of alcohol dependence. All subjects met criteria for AUD at baseline and
      were re-interviewed 5 years later. Follow-up status was categorized as persistent
      AUD, high-risk drinking, remitted low-risk drinking, and abstinence. Social
      context measures were defined as stable or changing from baseline to follow-up,
      and their bivariate and multivariate associations with follow-up status were
      tested. RESULTS: At follow-up, 62.8% of subjects had persistent AUD, 6.4% were
      high-risk drinkers, 22.2% were remitted low-risk drinkers, and 8.6% were
      abstinent. Birth of first child during the interval was the only measure of
      social context associated with remitted low-risk drinking and was significant for
      women only. Abstinent remission was characterized by being stably separated or
      divorced for women, new marriage for both sexes, experiencing low levels of
      family support and high levels of friend support, and receiving treatment. High
      risk drinkers were more likely than individuals with persistent AUD to have a
      stable number of children and to have been recently unemployed. CONCLUSIONS: The
      social contexts accompanying different types of remission in this high-risk
      sample resemble those found in population-based and clinical samples. Low-risk
      drinkers resemble natural remitters from population-based samples who change
      their drinking habits with life transitions. Abstainers resemble clinical samples
      in marital context, support from friends, and treatment. High-risk drinkers
      appear to continue to experience negative consequences of heavy drinking.

PMID- 24942363
TI  - Plasmonic enhancement of the optical absorption and catalytic efficiency of BiVO4
      photoanodes decorated with Ag@SiO2 core-shell nanoparticles.
AB  - Recent progress in the development of bismuth vanadate (BiVO4) photoanodes has
      firmly established it as a promising material for solar water splitting
      applications. Performance limitations due to intrinsically poor catalytic
      activity and slow electron transport have been successfully addressed through the
      application of water oxidation co-catalysts and novel doping strategies. The next
      bottleneck to tackle is the modest optical absorption in BiVO4, particularly
      close to its absorption edge of 2.4 eV. Here, we explore the modification of the
      BiVO4 surface with Ag@SiO2 core-shell plasmonic nanoparticles. A photocurrent
      enhancement by a factor of ~2.5 is found under 1 sun illumination (AM1.5). We
      show that this enhancement consists of two contributions: optical absorption and
      catalysis. The optical absorption enhancement is induced by the excitation of
      localized surface plasmon resonances in the Ag nanoparticles, and agrees well
      with our full-field electromagnetic simulations. Far-field effects (scattering)
      are found to be dominant, with a smaller contribution from near-field plasmonic
      enhancement. In addition, a significant catalytic enhancement is observed, which
      is tentatively attributed to the electrocatalytic activity of the Ag@SiO2
      nanoparticles.

PMID- 24942362
TI  - Clofarabine/cyclophosphamide for debulking before stem cell transplantation.
AB  - BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is the
      only curative rescue therapy for patients (pts) with chemotherapy-refractory
      acute leukaemia. Disease control prior to HSCT is essential for long-term disease
      free survival after HSCT. PATIENTS AND METHODS: We have retrospectively analysed
      the outcome of 20 pts aged 21-64 years with refractory leukaemia (acute myeloid
      leukaemia, n = 16; acute lymphatic leukaemia, n = 4) who received debulking
      therapy with clofarabine (10 mg/m2, days 1-4) and cyclophosphamide (200 mg/m2,
      days 1-4; ClofCy) prior to HSCT. RESULTS: Clofarabine/cyclophosphamide (1-4
      cycles) was well tolerated and resulted in a substantial reduction of leukaemic
      cells in all pts. HSCT was performed in 15 of 20 pts. After HSCT (myeloablative,
      n = 9; dose-reduced, n = 6), all pts showed engraftment and full donor chimerism
      (related donors, n = 4 or unrelated donors, n = 11) and all pts achieved complete
      haematologic remission (CR). The median survival after HSCT is 531 days (range:
      48-1462 days), and six pts are still alive after a median of 1245 days. Seven pts
      died after they had relapsed between days +152 and +1496. One patient died from
      acute graft-versus-host disease (day +48) and one from systemic fungal infection
      (day +87). CONCLUSION: Clofarabine/cyclophosphamide is a novel effective
      treatment approach for pts with chemotherapy-refractory acute leukaemia prior to
      HSCT. Whether this novel debulking protocol leads to improved long-term outcome
      in pts with refractory leukaemias remains to be determined in forthcoming
      clinical studies.

PMID- 24942365
TI  - Switchable supramolecular assemblies on graphene.
AB  - We studied the self-assembly of trimesic acid on single- and few-layer graphene
      supported by SiO2 substrates. A scanning tunneling microscope operated under
      ambient conditions was utilized to image supramolecular networks of trimesic acid
      at liquid-graphene interfaces. Trimesic acid can self-assemble into large-scale,
      highly ordered adlayers on graphene surfaces. Phase transition of the trimesic
      acid adlayer from a close-packed structure to a porous chicken-wire structure was
      observed by changing from single- to few-layer graphene, which was attributed to
      the modulation of molecule-graphene interactions by the layer number of graphene.
      The guest-induced phase transition of trimesic acid by complexation with coronene
      on single-layer graphene further confirms that supramolecular networks on
      graphene can be rationally tailored with sub-nanometer resolution by balancing
      between intermolecular vs. molecule-graphene interactions. We further
      investigated the effects of trimesic acid adlayers on the electronic transport
      properties of graphene transistors. The adsorption of trimesic acid induces p
      doping and defects in the adlayers cause scattering of charge carriers in single
      layer graphene. 

PMID- 24942366
TI  - Why mammalian wound-healing researchers may wish to turn to Drosophila as a
      model.
AB  - Wound healing is an essential and complex biological process that allows tissue
      continuity and functioning to be restored after injury. Understanding the
      molecular and cellular mechanisms underlying wound repair is essential to develop
      new therapies that could be useful not only to accelerate the normal healing
      process but also to treat healing pathologies that appear as a consequence of
      improper wound resolution. Numerous models have been developed to study wound
      healing both in vitro and in vivo. In vitro models have been useful to study some
      steps of epithelial repair. However, the development of effective treatments for
      wound healing is still required, and this could mainly be achieved using animal
      models. Although rodent models are currently preferred to study this process,
      they also have some limitations. Currently, the fruit fly Drosophila is a well
      established model to study processes relevant to human health and is becoming one
      of the favourite model organisms in biomedical research. The reason for this
      success is that it can be effectively used in target discovery and drug screens.
      In such a scenario, we would like to provide a defense for using Drosophila as an
      in vivo model of wound healing, assuming that many mammalian researchers may not
      be initially convinced with the idea. In this paper, we discuss the benefits and
      limitations of using Drosophila in wound-healing research, especially presenting
      this organism as a promising tool for the identification of new therapeutic
      targets and drugs in this context. 

PMID- 24942364
TI  - French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults.
AB  - INTRODUCTION: These guidelines are part of the French Experts' recommendations
      for the management of people living with HIV/AIDS, which were made public and
      submitted to the French health authorities in September 2013. The objective was
      to provide updated recommendations for antiretroviral treatment (ART) of HIV
      positive adults. Guidelines included the following topics: when to start, what to
      start, specific situations for the choice of the first session of antiretroviral
      therapy, optimization of antiretroviral therapy after virologic suppression, and
      management of virologic failure. METHODS: Ten members of the French HIV 2013
      expert group were responsible for guidelines on ART. They systematically reviewed
      the most recent literature. The chairman of the subgroup was responsible for
      drafting the guidelines, which were subsequently discussed within, and finalized
      by the whole expert group to obtain a consensus. Recommendations were graded for
      strength and level of evidence using predefined criteria. Economic considerations
      were part of the decision-making process for selecting preferred first-line
      options. Potential conflicts of interest were actively managed throughout the
      whole process. RESULTS: ART should be initiated in any HIV-positive person,
      whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of
      the individual benefit of ART in terms of mortality or progression to AIDS
      increases with decreasing CD4 cell count. Preferred initial regimens include two
      nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or
      abacavir/lamivudine) plus a non-nucleoside reverse transcriptase inhibitor
      (efavirenz or rilpivirine), or a ritonavir-boosted protease inhibitor (atazanavir
      or darunavir). Raltegravir, lopinavir/r, and nevirapine are recommended as
      alternative third agents, with specific indications and restrictions. Specific
      situations such as HIV infection in women, primary HIV infection, severe immune
      suppression with or without identified opportunistic infection, and person who
      injects drugs are addressed. Options for optimization of ART once virologic
      suppression is achieved are discussed. Evaluation and management of virologic
      failure are described, the aim of any intervention in such situation being to
      reduce plasma viral load to <50 copies/ml. CONCLUSION: These guidelines recommend
      that any HIV-positive individual should be treated with ART. This recommendation
      was issued both for the patient's own sake and for promoting treatment as
      prevention.

PMID- 24942367
TI  - Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma
      of salivary gland origin.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of
      minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral
      cavity and oropharynx, respectively. Controversy exists as to whether these
      tumors represent separate entities or variants of one spectrum, as they appear to
      have significant overlap, but also clinicopathologic differences. As many
      salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing
      and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs
      and two PLGAs. Validated rearrangements were then screened by fluorescence in
      situ hybridization (FISH) in 60 cases. Histologic classification was performed
      without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and
      21 with "mixed/indeterminate" features. The RNAseq of 2 CAMSGs showed ARID1A
      PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates were
      identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional
      cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 share
      similar functions with PRKD1 in the diacylglycerol and protein kinase C signal
      transduction pathway, we expanded the investigation for these genes by FISH. Six
      additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%)
      fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate
      cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and
      recurrent gene rearrangements in PRKD1-3 primarily in CAMSG, suggesting a
      possible pathogenetic dichotomy from "classic" PLGA. However, the presence of
      similar genetic findings in half of the indeterminate cases and a single PLGA
      suggests a possible shared pathogenesis for these tumor types.

PMID- 24942369
TI  - Sentinel lymph node mapping of melanoma using technetium-99m phytate by a hybrid
      single-photon emission computed tomography/computed tomography.

PMID- 24942368
TI  - The persistence of socially instructed threat: two threat-of-shock studies.
AB  - Learning to anticipate threat is crucial in guiding protective behavior. In
      classical conditioning, single trial learning can result in long-lasting fear
      associations. To examine whether threat learned through social communication is
      equally stable, an instructed fear paradigm was used with two repeated sessions
      on 1 day (Study 1; N = 43) and with separate sessions on 3 consecutive days
      (Study 2; N = 30). Startle EMG, skin conductance level (SCL), and self-report
      data were recorded during alternating periods of instructed threat and safety.
      Within 1 day, threat-potentiated startle was present across sessions but threat
      enhanced SCL decreased (Study 1). Across days, threat effects subsided with
      different timing for startle EMG, SCL, and self-report (Study 2). The present
      findings are a laboratory analog for the persistence of socially transmitted
      fear, which can be amazingly resistant to extinction (e.g., in specific phobias)
      even in the absence of aversive experiences.

PMID- 24942370
TI  - Newborn regional body composition is influenced by maternal obesity, gestational
      weight gain and the birthweight standard score.
AB  - AIM: This study investigated whether newborn body composition is influenced by
      prepregnancy obesity and gestational weight gain (GWG) and explored any
      associations between body composition and birthweight standard score (z-score),
      categorised by size for gestational age. METHODS: We recruited 231 obese and 80
      normal weight mothers and their newborn infants and assessed the babies' body
      composition using dual-energy X-ray absorptiometry. RESULTS: The total and
      abdominal fat masses of infants born to mother who were obese before pregnancy
      were 135 g (p < 0.001) and 18 g (p < 0.001) higher than the offspring of normal
      weight mothers. The infants' fat mass increased by 11 g (p < 0.001) for every
      kilogram of GWG. There were no associations between prepregnancy obesity and fat
      free mass. The fat percentage was significantly higher in infants who were large
      for gestational age (15.3%) than small for gestational age (5.2%) and appropriate
      for gestational age (9.8%) (p < 0.001). Lower birthweight z-score was associated
      with a higher proportion of abdominal fat mass (p = 0.009). CONCLUSION: Infants
      born to obese mothers had higher fat mass at birth, with abdominal fat
      accumulation. Low birthweight was associated with a lower crude abdominal fat
      mass, but a higher proportion of total fat mass placed abdominally.

PMID- 24942371
TI  - Tuberculosis of the Cuboid: A Case Report and Review of the Literature.
AB  - Tuberculosis (TB) remains a major global health problem. According to a recent
      World Health Organization report, it ranks as the second leading cause of death
      from an infectious disease worldwide. According to the "UK Health Protection
      Agency Tuberculosis in the UK: 2012 Report," 8963 cases were reported in the
      United Kingdom in 2011. London had the greatest proportion of cases in the United
      Kingdom and the greatest rate of disease. TB affecting the foot is rare,
      affecting about 10% of all skeletal TB cases. However, owing to the current
      patterns of global immigration, with significant volumes of people migrating out
      of endemic countries, it has become a disease that physicians and surgeons in
      developed countries should be more aware of in today's practice. To the best of
      our knowledge, we present the first adult case of TB of the cuboid in the United
      Kingdom and the first adult case documented outside of India. We present the case
      details and the results of a thorough review of the literature. TB of the foot
      and ankle poses a diagnostic challenge because of the propensity of TB to mimic
      other pathologic entities radiologically. Tissue diagnosis and antitubercular
      medication is the mainstay of diagnosis and treatment, respectively. 

PMID- 24942372
TI  - Surgical correction of checkrein deformity after malunited distal tibia fracture:
      a case report.
AB  - Checkrein deformities are rare and involve entrapment or tethering of the flexor
      hallucis longus and, occasionally, flexor digitorum longus tendons. The deformity
      has typically been secondary to traumatic fractures of the talus, calcaneus, or
      deep posterior compartment syndrome resulting from fractures of the tibia and
      fibula and most fractures of the ankle. These result in flexion contractures at
      the interphalangeal joint of the hallux. Because of the rarity of this deformity,
      no single surgical technique has been defined as the standard. Previous
      interventions have included release of adhesions with or without Z-plasty
      lengthening of the involved tendons. The present study reports a case of
      checkrein deformity secondary to a malunited distal tibia fracture, with flexion
      deformities to digits 1 through 3. The patient underwent successful surgical
      correction with flexor tenotomies to the affected digits with interphalangeal
      arthrodesis to the hallux.

PMID- 24942374
TI  - Amiodarone-induced epididymitis: a pathologically confirmed case report and
      review of the literature.
AB  - We report a case of amiodarone-induced epididymitis and review the pertinent
      literature. This disease is currently a diagnosis of exclusion and is believed to
      be self-limiting. We found new evidence for the pathological diagnosis and
      identified amiodarone-like crystals in the epididymis as a pathological mechanism
      of this disease. This case also suggests that amiodarone-induced epididymitis is
      not self-limiting. Continued use of amiodarone according to the current
      guidelines led to a bilateral epididymectomy. We recommend withdrawal or
      reduction of amiodarone dosage immediately once the signs and symptoms of
      epididymitis present in this population of patients. When epididymitis does not
      seem to be caused by an infection or any other identifiable etiology, this should
      not be overlooked by the cardiologist, urologist or general practitioner. These
      findings and recommendations should help reduce the suffering of patients and
      improve their clinical outcomes.

PMID- 24942373
TI  - The palindromic DNA-bound USP/EcR nuclear receptor adopts an asymmetric
      organization with allosteric domain positioning.
AB  - Nuclear receptors (NRs) regulate gene expression through DNA- and ligand-binding
      and thus represent crucial therapeutic targets. The ultraspiracle
      protein/ecdysone receptor (USP/EcR) complex binds to half-sites with a one base
      pair spaced inverted repeat (IR1), a palindromic DNA response element (RE)
      reminiscent of IRs observed for vertebrate steroid hormone receptors. Here we
      present the cryo electron microscopy structure of the USP/EcR complex bound to an
      IR1 RE which provides the first description of a full IR-bound NR complex. The
      structure reveals that even though the DNA is almost symmetric, the complex
      adopts a highly asymmetric architecture in which the ligand-binding domains
      (LBDs) are positioned 5' off-centred. Additional interactions of the USP LBD with
      the 5'-flanking sequence trigger transcription activity as monitored by
      transfection assays. The comparison with DR-bound NR complexes suggests that DNA
      is the major allosteric driver in inversely positioning the LBDs, which serve as
      the main binding-site for transcriptional regulators. 

PMID- 24942377
TI  - Highlights of topic "new trends on pathology of cholangiocarcinoma".

PMID- 24942375
TI  - Development and psychometric evaluation of the urgency questionnaire for
      evaluating severity and health-related quality of life impact of urinary urgency
      in overactive bladder.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary urgency is the cardinal symptom of
      overactive bladder (OAB). However, there is no single instrument that assesses
      the context, severity, intensity, and daily life impact of urinary urgency. The
      purpose of this manuscript is to describe the methods and results of the
      qualitative and quantitative research conducted to develop a new tool for this
      purpose, the Urgency Questionnaire (UQ). METHODS: Qualitative data from
      interviews with patients with urinary urgency were used to develop and refine the
      items and response options of the UQ. Three studies were used to evaluate
      psychometric properties: a clinical trial of tolterodine (Detrol; n = 974); a
      psychometric validation study (n = 163); and a test-retest validation study (n =
      47). Item and exploratory factor analysis (EFA) were performed to assess the
      subscale structure, and the psychometric performance of the resulting scales was
      evaluated. RESULTS: Fifteen Likert-scale items and four VAS questions were
      retained. A four-factor solution was shown to best fit the data, with the
      subscales: Impact on Daily Activities, Time to Control Urgency, Nocturia, and
      Fear of Incontinence. All subscales and VAS items demonstrated good reliability
      (Cronbach's alpha 0.79-0.94), convergent and discriminant validity, and
      responsiveness to change. The UQ differentiated between OAB patients and
      controls. CONCLUSION: The results provide quantitative evidence that urinary
      urgency, as assessed by the UQ, is a pathological sensation distinctive from the
      normal urge to void and suggest that the UQ might be a reliable, valid, and
      responsive instrument for evaluating the severity and HRQL impact of urinary
      urgency in OAB.

PMID- 24942376
TI  - Lentivirus-mediated RNA interference against Japanese encephalitis virus
      infection in vitro and in vivo.
AB  - Japanese encephalitis virus, a serious mosquito-borne flavivirus, causes acute
      encephalitis in humans and many animals, with a high fatality rate. RNA
      interference is a reasonable antiviral mechanism for target gene silencing. In
      this study, four lentiviral shRNAs (LV-E1, LV-E2, LV-NS3 and LV-NS4b) were
      constructed. The results showed that four recombinant lentiviruses suppressed JEV
      replication in vitro. Through treatment with LV-E1 or LV-E2, the TCID50 values
      were reduced by 10(3)-fold during 120h post-challenge; the relative expression of
      viral mRNA was <7% or 13% in mouse and human neuroblastoma cells. Lentiviral
      shRNAs displayed robust inhibitory activity in various cells and against
      different genotypes of JEV. In vivo, pre-treatments of LV-E1 or LV-E2 resulted in
      no viral particles being observed in suckling mice brain sections. For 21days of
      observation, 100% of mice were protected against lethal JEV injection by two pre
      treatments with LV-E1 or LV-E2; the survival of the mice pre-challenged with
      lethal JEV was 88.3%/66.7% by treatment with LV-E1 or LV-E2. LV-E1 and LV-E2
      suppressed the induction of inflammatory mediators effectively in neuroblastoma
      cells and mice. Lentiviral shRNAs significantly inhibit JEV infection for long
      term in vitro and in vivo and effectively reduce the inflammatory response and
      relieve encephalitis symptoms, highlighting the feasibility of using lentivirus
      mediated RNAi for potential therapy in JEV infection. 

PMID- 24942378
TI  - BK Virus and Its Role in Hematopoietic Stem Cell Transplantation: Evolution of a
      Pathogen.
AB  - We reviewed the literature regarding disease induced by BK virus (BKV) in the
      hematopoietic stem cell transplant (HSCT) population, particularly hemorrhagic
      cystitis (HC) and nephritis. The association between BKV and HC has been reported
      over the past four decades. BKV has been clinically implicated and widely
      accepted as an etiologic agent of HC and nephritis in HSCT and nephropathy in
      renal transplant patients. We discuss the potential benefit of early initiation
      of therapy in patients who fail supportive care alone as well as the different
      treatment strategies for HC induced by BKV. Treatments that have been used such
      as cidofovir and leflunomide are accompanied by risks, and the benefits are not
      as concrete as with other viral illness in the HSCT population. 

PMID- 24942379
TI  - Effective immobilization of BMP-2 mediated by polydopamine coating on
      biodegradable nanofibers for enhanced in vivo bone formation.
AB  - Although bone morphogenic proteins (BMPs) have been widely used for bone
      regeneration, the ideal delivery system with optimized dose and minimized side
      effects is still active area of research. In this study, we developed bone
      morphogenetic protein-2(BMP-2) immobilized poly(l-lactide) (PLLA) nanofibers
      inspired by polydopamine, which could be ultimately used as membranes for guided
      bone regeneration, and investigated their effect on guidance of in vitro cell
      behavior and in vivo bone formation. Surface chemical analysis of the nanofibers
      confirmed successful immobilization of BMP-2 mediated by polydopamine, and about
      90% of BMP-2 was stably retained on the nanofiber surface for at least 28 days.
      The alkaline phosphatase activity and calcium mineralization of human mesenchymal
      stem cells (hMSCs) after 14 days of in vitro culture was significantly enhanced
      on nanofibers immobilized with BMP-2. More importantly, BMP-2 at a relatively
      small dose was highly active following implantation to the critical-sized defect
      in the cranium of mice; radiographic analysis demonstrated that 77.8 +/- 11.7% of
      newly formed bone was filled within the defect for a BMP-2-immobilized groups at
      the concentration of 124 +/- 9 ng/cm(2), as compared to 5.9 +/- 1.0 and 34.1 +/-
      5.5% recovery, for a defect-only and a polydopamine-only group, respectively.
      Scanning and transmission electron microscopy of samples from the BMP-2
      immobilized group showed fibroblasts and osteoblasts with nanofiber strands in
      the middle of regenerated bone tissue, revealing the importance of interaction
      between implanted nanofibers and the neighboring extracellular environment. Taken
      together, our data support that the presentation of BMP-2 on the surface of
      nanofibers as immobilized by utilizing polydopamine chemistry may be an effective
      method to direct bone growth at relatively low local concentration. 

PMID- 24942380
TI  - Phototherapy in skeletal muscle performance and recovery after exercise: effect
      of combination of super-pulsed laser and light-emitting diodes.
AB  - Recent studies with phototherapy have shown positive results in enhancement of
      performance and improvement of recovery when applied before exercise. However,
      several factors still remain unknown such as therapeutic windows, optimal
      treatment parameters, and effects of combination of different light sources
      (laser and LEDs). The aim of this study was to evaluate the effects of
      phototherapy with the combination of different light sources on skeletal muscle
      performance and post-exercise recovery, and to establish the optimal energy dose.
      A randomized, double-blinded, placebo-controlled trial with participation of 40
      male healthy untrained volunteers was performed. A single phototherapy
      intervention was performed immediately after pre-exercise (baseline) maximum
      voluntary contraction (MVC) with a cluster of 12 diodes (4 of 905 nm lasers
      0.3125 mW each, 4 of 875 nm LEDs-17.5 mW each, and 4 of 670 nm LEDs-15 mW each-
      manufactured by Multi Radiance MedicalTM) and dose of 10, 30, and 50 J or placebo
      in six sites of quadriceps. MVC, delayed onset muscle soreness (DOMS), and
      creatine kinase (CK) activity were analyzed. Assessments were performed before, 1
      min, 1, 24, 48, 72, and 96 h after eccentric exercise protocol employed to induce
      fatigue. Phototherapy increased (p < 0.05) MVC was compared to placebo from
      immediately after to 96 h after exercise with 10 or 30 J doses (better results
      with 30 J dose). DOMS was significantly decreased compared to placebo (p < 0.05)
      with 30 J dose from 24 to 96 h after exercise, and with 50 J dose from
      immediately after to 96 h after exercise. CK activity was significantly decreased
      (p < 0.05) compared to placebo with all phototherapy doses from 1 to 96 h after
      exercise (except for 50 J dose at 96 h). Pre-exercise phototherapy with
      combination of low-level laser and LEDs, mainly with 30 J dose, significantly
      increases performance, decreases DOMS, and improves biochemical marker related to
      skeletal muscle damage. 

PMID- 24942381
TI  - The estimated frequency of antiphospholipid antibodies in young adults with
      cerebrovascular events: a systematic review.
AB  - BACKGROUND: Around 10% of all thrombotic cerebrovascular events (CVE) occur in
      young population and in a large proportion of those the trigger remains
      undetermined. Antiphospholipid antibodies (aPL) are recognised risk factors for
      ischaemic stroke and recurrent thrombotic events; however, the frequency of aPL
      in young people with CVE is still an unresolved issue. OBJECTIVES: To estimate
      the frequency of aPL in young adults with CVE and to determine whether aPL
      positive young individuals are at greater risk of CVE when compared with
      individuals without aPL by systematically reviewing the literature. METHODS:
      Medline reports published between 1970 and 2013 investigating the presence of aPL
      in young patients (<50 years old) with CVE were included. The median frequency
      for positive aPL, including lupus anticoagulant, anticardiolipin antibodies (aCL)
      and antibodies against beta2Glycoprotein I (anti-beta2GPI), was calculated for
      stroke and transient ischaemic attacks. FINDINGS: This systematic review is based
      on available data from 5217 patients and controls from 43 studies analysing the
      frequency of aPL in young patients with CVE. The overall aPL frequency was
      estimated as 17.4% (range 5%-56%) for any CVE, 17.2% (range 2%-56%) for stroke
      and 11.7% (range 2%-45%) for transient ischaemic attack (TIA). The presence of
      aPL increased the risk for CVE by 5.48-fold (95% CI 4.42 to 6.79). Based on
      available data, the frequency of aPL in young patients with CVE can be estimated
      at 17%, rising up to 22% for aCL in patients with stroke. The presence of aPL
      seems to confer a fivefold higher risk for stroke or TIA when compared with
      controls. However, variability in test reproducibility and cut-off definition
      still represent an important methodological limitation for the current diagnostic
      testing for aPL. These observations should be confirmed by appropriately designed
      population studies.

PMID- 24942382
TI  - Improvements in productivity at paid work and within the household, and increased
      participation in daily activities after 24 weeks of certolizumab pegol treatment
      of patients with psoriatic arthritis: results of a phase 3 double-blind
      randomised placebo-controlled study.
AB  - OBJECTIVES: To evaluate the effect of certolizumab pegol (CZP) on productivity
      outside and within the home, and on participation in family, social and leisure
      activities in adult patients with psoriatic arthritis (PsA). METHODS: RAPID-PsA
      (NCT01087788) is a phase 3, double-blind, placebo-controlled trial. 409 patients
      with active PsA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W)
      or CZP 400 mg every 4 weeks (Q4W). The arthritis-specific Work Productivity
      Survey (WPS) assessed the impact of PsA on paid work and household productivity,
      and participation in social activities during the preceding month. WPS responses
      were compared between treatment arms using a non-parametric bootstrap-t method.
      RESULTS: At baseline, 56.6%, 60.1% and 61.5% of placebo, CZP 200 mg Q2W and CZP
      400 mg Q4W patients were employed. By week 24, employed CZP patients reported an
      average of 1.0-1.8 and 3.0-3.9 fewer days of absenteeism and presenteeism,
      respectively, per month compared with 1.0 and 0.3 fewer days for placebo patients
      (p<0.05). Within the home, by week 24, CZP patients reported an average of 3.0
      3.5 household work days gained per month versus 1.0 day for placebo (p<0.05). CZP
      patients also reported fewer days with reduced household productivity or days
      lost for participation in family, social and leisure activities. Improvements
      with CZP were seen as early as week 4 and continued to week 24. CONCLUSIONS: CZP
      treatment significantly improved productivity at paid work and within the home,
      and resulted in greater participation in social activities for PsA patients.
      TRIAL REGISTRATION NUMBER: NCT01087788.

PMID- 24942384
TI  - Developments in FT-ICR MS instrumentation, ionization techniques, and data
      interpretation methods for petroleomics.
AB  - Because of the increasing importance of heavy and unconventional crude oil as an
      energy source, there is a growing need for petroleomics: the pursuit of more
      complete and detailed knowledge of the chemical compositions of crude oil. Crude
      oil has an extremely complex nature; hence, techniques with ultra-high resolving
      capabilities, such as Fourier transform ion cyclotron resonance mass spectrometry
      (FT-ICR MS), are necessary. FT-ICR MS has been successfully applied to the study
      of heavy and unconventional crude oils such as bitumen and shale oil. However,
      the analysis of crude oil with FT-ICR MS is not trivial, and it has pushed
      analysis to the limits of instrumental and methodological capabilities. For
      example, high-resolution mass spectra of crude oils may contain over 100,000
      peaks that require interpretation. To visualize large data sets more effectively,
      data processing methods such as Kendrick mass defect analysis and statistical
      analyses have been developed. The successful application of FT-ICR MS to the
      study of crude oil has been critically dependent on key developments in FT-ICR MS
      instrumentation and data processing methods. This review offers an introduction
      to the basic principles, FT-ICR MS instrumentation development, ionization
      techniques, and data interpretation methods for petroleomics and is intended for
      readers having no prior experience in this field of study.

PMID- 24942383
TI  - Impact of advanced age on the severity of normotensive pulmonary embolism.
AB  - The prevalence of pulmonary embolism (PE) increases progressively with age. Less
      data about the impact of increasing age on the severity of PE are available. The
      objectives of this study were to investigate the impact of increasing age on the
      severity of normotensive PE. Retrospective analysis of clinical, laboratory,
      radiological and echocardiagraphic data of normotensive patients with PE was
      performed. According to patients' age at the moment of acute PE event, the total
      number of 129 normotensive PE patients was subdivided into 4 age groups. In age
      groups 18-59, 60-69, 70-79 and 80-94 years were, respectively, a number of 30,
      31, 33 and 35 patients included. Percentage of women in age groups increased with
      advanced age (P = 0.021). Systolic pulmonary artery pressure (PAP) (P < 0.0001)
      and frequency of incomplete or complete right bundle-branch block (RBBB) (P =
      0.019), of right ventricular dysfunction (RVD) (P = 0.00031) and of submassive PE
      stadium with intermediate risk (P = 0.0016) increased significantly with growing
      age. Multivariable regression model confirmed an association between age and
      submassive PE [OR (per year) 1.04; 95 % CI, 1.02-1.07, P = 0.0020] as well as
      female gender and submassive PE (OR 2.45; 95 % CI, 1.10-5.50, P = 0.029) and
      tachycardia and submassive PE (OR 15.33; 95 % CI, 3.45-68.24, P = 0.00034).
      Advanced age, female gender and tachycardia are risk factors for a submassive PE
      with intermediate risk in normotensive PE patients. The percentage of PE patients
      with submassive PE, right ventricular overload, RVD, RBBB, elevated systolic PAP
      increases with advanced age. 

PMID- 24942385
TI  - Comparing the immediate effects of UCBL and modified foot orthoses on postural
      sway in people with flexible flatfoot.
AB  - BACKGROUND: Different types of foot orthoses have been prescribed for patients
      with flatfoot. Results of several studies have shown that orthoses were able to
      change balance parameters in people with flatfoot. However, the possible effect
      of orthosis flexibility on balance has not yet been investigated. OBJECTIVES: The
      aim of the current study was to investigate the immediate effect of a rigid
      University of California Berkeley Laboratory (UCBL) foot orthosis, a modified
      foot orthosis, and a normal shoe on the postural sway of people with flexible
      flatfoot. STUDY DESIGN: Quasi-experimental. METHODS: In all, 20 young adults with
      flatfoot (aged 23.5 +/- 2.8 years) were invited to participate in this study. The
      Biodex Stability System was employed to perform standing balance tests under
      three testing conditions, namely, shoe only, UCBL, and modified foot orthosis.
      Total, medial-lateral, and anterior-posterior sway were evaluated for each
      condition. RESULTS: The results of this study revealed no statistical difference
      in the medial-lateral and anterior-posterior stability indices between foot
      orthoses and shoed conditions. The overall stability index with the UCBL foot
      orthosis, however, was significantly lower than that with the modified foot
      orthosis. CONCLUSION: The UCBL foot orthosis was able to decrease total sway and
      improve balance in people with flexible flatfoot. CLINICAL RELEVANCE: Results of
      previous studies have indicated that foot orthoses were able to affect the
      balance of people with flatfeet. However, the possible effects of flexible
      orthoses on balance have not been examined. The results of this study may provide
      new insight into material selection for those people with balance disorders.

PMID- 24942386
TI  - Development of a cosmetic knee disarticulation prosthesis: A single-patient case
      study.
AB  - BACKGROUND AND AIM: If a person does not become ambulant after an amputation, a
      knee disarticulation (KD) shouldbe considered and the person may then benefit
      from a cosmetic KD prosthesis. The features of a cosmetic KD prosthesis are,
      however, seldom described. The aim of this clinical note is to describe the
      development of a cosmeticKD prosthesis. TECHNIQUE: A non-ambulant person with
      bilateral KD formulated, together with her physiatrist, the criteria for a
      cosmetic KD prosthesis. On the basis of these, a lightweight, natural-looking,
      well-fitting, easy-to-put-on and take-off KD prosthesis, with no thigh
      lengthening during sitting, was made. This prosthesis was fixed on a wheelchair
      and does not impede transfer. DISCUSSION: A newly constructed cosmetic prosthesis
      for non-ambulant persons with a KD is described in detail. We hope that this will
      encourage physiatrists and prosthetists to offer non-ambulant persons with a KD a
      cosmetic prosthesis. CLINICAL RELEVANCE: A cosmetic leg prosthesis with good
      cosmetic properties, good sitting comfort, and no restrictions in making
      transfers is described in detail for non-ambulant persons with a knee
      disarticulation.

PMID- 24942387
TI  - Calprotectin induces cell death in human prostate cancer cell (LNCaP) through
      survivin protein alteration.
AB  - Calprotectin (CP), an abundant heterodimeric cytosolic protein of neutrophils,
      conveys a variety of functions such as tumor cell growth arrest and antimicrobial
      activity. We investigated CP activity and its possible apoptosis-inducing
      mechanism of action against an antiandrogen therapy-resistance prostate cancer
      cell line LNCaP. Cell viability and Annexin V FITC assays were performed in order
      to investigate its cell death activity and apoptosis, respectively. In order to
      address cell death inducing mechanism(s), immunocytochemistry and immunobloting
      analysis, reactive oxygen species (ROS) and nitric oxide (NO) measurements were
      performed. The effective concentration of CP against LNCaP promoting LNCaP cell
      death was 200 ug/mL. ROS and NO levels of cells remarkably were enhanced
      following treatment with 50 and 100 ug/mL of CP, respectively. Protein expression
      of anti-apoptotic protein survivin was significantly decreased after
      administration of tumor cells with CP. Our data indicate that CP regulates the
      LNCaP cells viability via survivin-mediated pathway and ROS and NO enhancement.
      Thus, inhibition of survivin expression, enhancement of ROS and NO level by CP or
      other similar pharmaceutical agents might be effective in lowering the malignant
      proliferation of human prostate cancer cells. 

PMID- 24942389
TI  - Laboratory tests to identify patients at risk of early major adverse events: a
      prospective pilot study.
AB  - BACKGROUND/AIMS: To test whether commonly measured laboratory variables can
      identify surgical patients at risk of major adverse events (death, unplanned
      intensive care unit (ICU) admission or rapid response team (RRT) activation).
      METHODS: We conducted a prospective observational study in a surgical ward of a
      university-affiliated hospital in a cohort of 834 surgical patients admitted for
      >24 h. We applied a previously validated multivariable model-derived risk
      assessment to each combined set of common laboratory tests to identify patients
      at risk. We compared the clinical course of such patients with that of control
      patients from the same ward who had blood tests but were identified as low risk.
      RESULTS: We studied 7955 batches and 73,428 individual tests in 834 patients
      (males 55%; average age 65.8 +/- 17.6 years). Among these patients, 66 (7.9%)
      were identified as 'high risk'. High-risk patients were older (75.9 vs 61.8 years
      of age; P < 0.0001), had much greater early (48 h) mortality (6/66 (9%) vs 4/768
      (0.5%); P < 0.0001) and greater overall hospital mortality (11/66 (16.7%) vs
      9/768 (1.2%); P < 0.0001). They also had more early (8/66 (12.1%) vs 14/768
      (1.8%); P = 0.0001) and overall in-hospital unplanned ICU admissions (12/66
      (18.2%) vs 18/768 (2.3%); P < 0.0001) and more early (26/66 (39.3%) vs 50/768
      (6.5%); P < 0.0001) and overall in-hospital RRT calls (26/66 (39.4%) vs 55/768
      (7.2%); P < 0.0001). CONCLUSIONS: Commonly performed laboratory tests identify
      surgical ward patients at risk of early major adverse events. Further studies are
      needed to assess whether such identification system can be used to trigger
      interventions that help improve patient outcomes.

PMID- 24942388
TI  - Drug treatment for attention-deficit/hyperactivity disorder and suicidal
      behaviour: register based study.
AB  - OBJECTIVE: To investigate the association between drug treatment for attention
      deficit/hyperactivity disorder (ADHD) and risk of concomitant suicidal behaviour
      among patients with ADHD. DESIGN: Register based longitudinal study using within
      patient design. SETTING: Linkage of multiple national registers in Sweden.
      PARTICIPANTS: 37,936 patients with ADHD born between 1960 and 1996 and followed
      from 2006 to 2009 for treatment status by ADHD drug treatment and suicide related
      events (suicide attempt and completed suicide). MAIN OUTCOME MEASURE: Incidence
      rate of suicide related events during ADHD drug treatment periods compared with
      that during non-treatment periods. RESULTS: Among 37,936 patients with ADHD, 7019
      suicide related events occurred during 150,721 person years of follow-up. At the
      population level, drug treatment of ADHD was associated with an increased rate of
      suicide related events (hazard ratio 1.31, 95% confidence interval 1.19 to 1.44).
      However, the within patient comparison showed a reverse association between ADHD
      drug treatment and rate of suicide related events (0.89, 0.79 to 1.00). Among
      stimulant users, a reduced within patient rate of suicide related events was seen
      during treatment periods (0.81, 0.70 to 0.94). Among non-stimulant/mixed users,
      no significantly increased within patient rate of suicide related events during
      non-stimulant treatment periods was seen (0.96, 0.72 to 1.30). CONCLUSIONS: This
      study found no evidence for a positive association between the use of drug
      treatments for ADHD and the risk of concomitant suicidal behaviour among patients
      with ADHD. If anything, the results pointed to a potential protective effect of
      drugs for ADHD on suicidal behaviour, particularly for stimulant drugs. The study
      highlights the importance of using within patient designs to control for
      confounding in future pharmacoepidemiological studies.

PMID- 24942391
TI  - Physical activity in the management of patients with coronary artery disease: a
      review.
AB  - Cardiovascular diseases remain the leading cause of death in the Western world
      despite advances in therapeutics and interventions. The prescription of physical
      activity is a key component of cardiac rehabilitation following myocardial
      infarction. This review aims to outline the impact of physical activity in
      particular patient cohorts with coronary artery disease. The current
      understanding of the mechanisms involved in atherosclerosis, plaque rupture and
      thrombosis, and how these can be modified by physical activity, are also
      discussed. There is the potential for future research to investigate the clinical
      and mechanistic effects of different exercise types, intensities, duration, and
      frequencies in patients hospitalized for coronary artery disease. 

PMID- 24942390
TI  - Wolffian duct development.
AB  - The Wolffian ducts (WDs) are the progenitors of the epididymis, vas deferens and
      seminal vesicles. They form initially as nephric ducts that acquire connection to
      the developing testis as the mesonephros regresses. The development of the WDs is
      dependent on androgens. Conventionally, the active androgen is believed to be
      testosterone delivered locally rather than via the systemic circulation. However,
      recent studies in marsupials show that 5alpha-reduced steroids are essential and
      that these can induce virilisation even when they are delivered via the systemic
      circulation. The development of the WDs involves an interplay between the duct
      epithelium and underlying mesenchyme; androgen receptors in both the epithelium
      and mesenchyme are needed. The epidermal growth factor and epidermal growth
      factor receptor may play a role, possibly via activation of androgen receptor.
      The formation of the epididymis involves a complex morphogenetic program to
      achieve the normal pattern of coiling, formation of septae, and regional
      functional differentiation. In part, this process may be mediated by inhibin beta
      A as well as by genes from the HOX cluster. Whilst the development of the WD is
      androgen dependent, it is clear that there is a complex interplay between
      androgens, genes and growth factors in the tissues that leads to the formation of
      the complex anatomy of the male reproductive duct system in the adult.

PMID- 24942393
TI  - Reducing elevated plasma LDL cholesterol: the central role of the LDL receptor.
AB  - Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk
      factor for cardiovascular disease (CVD), and reduction of elevated LDL-C reduces
      mortality in patients at risk. This benefit has evolved from the use of statins
      and knowledge of the LDL receptor (LDLR). The most potent drugs used for
      dyslipidemias act by mechanisms that involve this receptor. Advances in molecular
      genetics and understanding of the regulation of this receptor have revealed
      several pharmacological targets that are being explored to develop more targeted
      therapies for dyslipidemias. 

PMID- 24942396
TI  - Patients benefit from genetics-guided coumarin anticoagulant therapy.
AB  - Observational studies have overwhelmingly shown that variants in the genes CYP2C9
      and VKORC1 are significant determinants of individual dose of coumarin
      anticoagulants needed to maintain a therapeutic international normalized ratio
      (INR).(1) Until recently, however, few randomized clinical trials had been
      performed relating to the use of genetic data to predict dosing. Three sucsh
      clinical trials have now reported their findings. 

PMID- 24942397
TI  - New oral anticoagulants vs. warfarin treatment: no need for pharmacogenomics?
AB  - For patients requiring long-term anticoagulation, oral vitamin K antagonists
      (VKAs) such as warfarin have overwhelming efficacy data and present significant
      challenges. In addition to the potential exposure to numerous drug-drug and drug
      food interactions, patients receiving warfarin require frequent monitoring. It
      had been hoped that the integration of pharmacogenomic with clinical information
      would improve anticoagulation control with warfarin, but trials have not
      supported this aim. Novel oral anticoagulants (NOACs) offer both advantages and
      disadvantages and deserve consideration in appropriate patients. 

PMID- 24942399
TI  - Warfarin pharmacogenetics: to genotype or not to genotype, that is the question.
AB  - Genotype is well recognized to influence the dose of warfarin necessary for
      therapeutic anticoagulation. Recent randomized controlled trials evaluating the
      clinical utility of genotype-guided warfarin dosing have produced varying
      results. We review the design and results of the recent clinical trials, assess
      the impact of their findings on warfarin dosing, and examine unanswered questions
      related to clinical implementation of warfarin pharmacogenetics. 

PMID- 24942398
TI  - Measurement of low-density lipoprotein cholesterol in assessment and management
      of cardiovascular disease risk.
AB  - The deposition of cholesterol in the arterial wall by the infiltration of low
      density lipoproteins (LDLs) is a key step in the development of atherosclerosis.
      In this Commentary, we discuss recent recommendations for clinical laboratory
      measurement of low-density lipoprotein cholesterol (LDL-C) and its utility both
      for assessing cardiovascular disease risk and as a tool in the management of
      patients receiving lipid-lowering therapy. 

PMID- 24942400
TI  - Pancreaticogastrostomy versus pancreaticojejunostomy.
AB  - BACKGROUND: It has long been debated whether pancreaticogastrostomy (PG) or
      pancreaticojejunostomy (PJ) is the better choice for reconstruction after
      pancreaticoduodenectomy. The purpose of this study is to evaluate the two
      techniques. METHODS: Randomized controlled trials (RCTs) comparing PG with PJ
      published from January 1995 to January 2014 were searched electronically using
      PubMed, Medline, and Cochrane Library. Published data of these RCTs were analyzed
      using either fixed-effects model or random-effects model. RESULTS: Seven RCTs
      were included in this meta-analysis, with a total of 1121 patients (562 in PG,
      559 in PJ). The incidence of postoperative pancreatic fistula and intra-abdominal
      fluid collection were significantly lower in PG than in PJ (respectively: odds
      ratio = 0.53 [0.37, 0.74], P < 0.001; odds ratio = 0.48 [0.30, 0.76], P < 0.01),
      no significant difference could be found for delayed gastric emptying,
      hemorrhage, morbidity, reoperation rate, and mortality. CONCLUSIONS: The evidence
      from RCTs suggests that PG technique is associated with a lower rate of
      postoperative pancreatic fistula and intra-abdominal fluid collection than PJ.

PMID- 24942401
TI  - Pulmonary vein isolation using a circular, open irrigated mapping and ablation
      catheter (nMARQ): a report on feasibility and efficacy.
AB  - AIMS: Pulmonary vein isolation (PVI) is the mainstay of interventional treatment
      of paroxysmal atrial fibrillation (PAF). We report on the feasibility and
      efficacy of a novel, open-irrigated mapping and radiofrequency (RF) ablation
      catheter. METHODS AND RESULTS: Thirty-nine consecutive patients (pts; age 60 +/-
      10 years, 8 females) suffering from drug-refractory PAF referred for PVI were
      included in this prospective study. Pulmonary vein isolation was performed with
      the use of a novel 10-pole circular, open-irrigated mapping and ablation catheter
      (nMARQ, Biosense Webster). Outcome parameters were the acute success rate in
      establishing complete PVI and the rate of sustained sinus rhythm (SR) during
      follow-up (FU). Ten patients underwent a repeat procedure for recurrent AF.
      Ninety-eight percent of the PVs could be acutely isolated using solely the nMARQ
      catheter by applying a mean total of 10.0 +/- 4.6 min of RF energy. The mean
      total procedure duration was 86 +/- 29 min, and the mean fluoroscopy time was
      22.2 +/- 6.5 min, respectively. Transient reconnection provoked by adenosine was
      observed in 10 of 24 patients, most frequently in the right superior PV. Cardiac
      tamponade related to transseptal puncture occurred in one patient. Reconnected
      PVs could be identified as a source of recurrent AF in 9 of 10 patients
      undergoing a repeat procedure. Single and multiple procedure success rates during
      a mean FU of 140 +/- 75 days were 66 and 77%, respectively. CONCLUSION: Irrigated
      multi-electrode RF ablation is fast and effective, providing a high rate of
      isolated PVs without the need of touch-up lesions. Success rates were comparable
      with other techniques with a low complication rate. Recurrences of AF were mainly
      due to recovered pulmonary vein/left atrium conduction.

PMID- 24942402
TI  - Left superior pulmonary vein ectopic rhythm mimicking normal sinus rhythm.

PMID- 24942403
TI  - New diagnostic criteria for identifying left-sided ventricular ectopy using non
      contact mapping and virtual unipolar electrogram analysis.
AB  - AIMS: To assess the efficacy of non-contact mapping for outflow tract premature
      ventricular contraction (PVC) and ventricular tachycardia (VT) ablation in
      patients without structural heart disease and a precordial transition at V3 or
      later and to determine the diagnostic accuracy of new virtual unipolar
      electrogram criteria for distinguishing left from right-sided foci using a multi
      electrode array positioned within the right ventricular outflow tract. METHODS
      AND RESULTS: Virtual unipolar electrograms at early activation (EA) and break out
      (BO) sites in 100 patients (36 left-sided foci) who underwent acutely successful
      outflow tract ablation were analysed and voltage and timing-based criteria
      measured. The best performing parameters were then re-assessed in 41 patients (14
      left-sided) prospectively. Of the candidate criteria for determining a left from
      right-sided focus, the voltage at 20 ms after EA (EA-V20) and the time from BO to
      QRS onset (BO-QRS) were the best discriminators with area under the curve (AUC)
      values based on receiver operator characteristics (ROCs) of 0.947 (0.905-0.989),
      P < 0.001, and 0.951 (0.907-0.995), P < 0.001, respectively. These two parameters
      were subsequently assessed prospectively in a further 41 patients (14 left-sided)
      using the pre-specified cut-off values of -2 mV for EA-V20 and 10 ms for BO-QRS
      which demonstrated excellent diagnostic accuracy and sufficient inter-beat and
      inter-observer reproducibility. CONCLUSIONS: This large single-centre experience
      demonstrates that a strategy for outflow tract PVC/VT ablation using non-contact
      mapping allows for excellent success rates. Furthermore, detailed analysis of
      virtual unipolar electrograms allows accurate and reproducible determination of
      left from right-sided foci that may be used to guide mapping and ablation.

PMID- 24942405
TI  - Spinal cord cavernous angiomas: a case report.

PMID- 24942406
TI  - Relationship between serum cholesterol efflux capacity and glucose intolerance in
      Japanese-Americans.
AB  - AIM: Serum cholesterol efflux has been suggested to be a key anti-atherogenic
      function of reverse cholesterol transport. Meanwhile, the quantitative and
      qualitative alteration of the levels of lipoproteins in the serum has been
      reported in patients with diabetes, although it remains unclear whether the serum
      cholesterol efflux capacity is impaired in cases of newly diagnosed glucose
      intolerance. We thus assessed the relationship between the serum cholesterol
      efflux capacity and glucose intolerance as detected using oral glucose tolerance
      tests (OGTTs). METHODS: We measured the capacity of whole serum to mediate
      cholesterol efflux from human THP-1 macrophages in a cohort of 439 Japanese
      Americans who underwent 75-g OGTTs. A multiple regression analysis was performed
      to examine the relationship between the serum cholesterol efflux capacity and
      glucose intolerance. RESULTS: The serum cholesterol efflux capacity was found to
      be negatively correlated with the area under the curve for the serum glucose
      concentration during the 75-g OGTTs in all subjects. In addition, the serum
      cholesterol efflux capacity was found to be modestly but significantly lower in
      the glucose intolerance group (31.4 +/- 6.2%) than in the normal glucose
      tolerance group (33.2 +/- 6.1%). There was also a negative association between
      the serum cholesterol efflux capacity and glucose intolerance after adjusting for
      age and sex. Moreover, this association remained significant even after further
      adjustments for serum total cholesterol, high-density lipoprotein cholesterol,
      apolipoprotein AI and C-reactive protein. CONCLUSIONS: The serum cholesterol
      efflux capacity is impaired in Japanese-Americans newly diagnosed with glucose
      intolerance. This impairment may contribute in some manner to increasing the risk
      of atherosclerotic disease in subjects with glucose intolerance.

PMID- 24942404
TI  - Preclinical analyses and phase I evaluation of LY2603618 administered in
      combination with pemetrexed and cisplatin in patients with advanced cancer.
AB  - LY2603618 is an inhibitor of checkpoint kinase 1 (CHK1), an important regulator
      of the DNA damage checkpoints. Preclinical experiments analyzed NCI-H2122 and NCI
      H441 NSCLC cell lines and in vitro/in vivo models treated with pemetrexed and
      LY2603618 to provide rationale for evaluating this combination in a clinical
      setting. Combination treatment of LY2603618 with pemetrexed arrested DNA
      synthesis following initiation of S-phase in cells. Experiments with tumor
      bearing mice administered the combination of LY2603618 and pemetrexed
      demonstrated a significant increase of growth inhibition of NCI-H2122 (H2122) and
      NCI-H441 (H441) xenograft tumors. These data informed the clinical assessment of
      LY2603618 in a seamless phase I/II study, which administered pemetrexed (500
      mg/m(2)) and cisplatin (75 mg/m(2)) and escalating doses of LY2603618: 130-275
      mg. Patients were assessed for safety, toxicity, and pharmacokinetics. In phase
      I, 14 patients were enrolled, and the most frequently reported adverse events
      included fatigue, nausea, pyrexia, neutropenia, and vomiting. No DLTs were
      reported at the tested doses. The systemic exposure of LY2603618 increased in a
      dose-dependent manner. Pharmacokinetic parameters that correlate with the maximal
      pharmacodynamic effect in nonclinical xenograft models were achieved at doses
      >=240 mg. The pharmacokinetics of LY2603618, pemetrexed, and cisplatin were not
      altered when used in combination. Two patients achieved a confirmed partial
      response (both non-small cell lung cancer), and 8 patients had stable disease.
      LY2603618 administered in combination with pemetrexed and cisplatin demonstrated
      an acceptable safety profile. The recommended phase II dose of LY2603618 was 275
      mg.

PMID- 24942407
TI  - Pharmacodynamic effects of cilostazol versus clopidogrel in stented patients
      under proton pump inhibitor co-administration: the ACCEL-PARAZOL study.
AB  - AIM: Proton pump inhibitor (PPI) therapy has been shown to attenuate the
      antiplatelet effects of clopidogrel. The aim of this study was to compare the
      antiplatelet effects of cilostazol versus clopidogrel in patients co-administered
      a PPI. METHODS: We enrolled PPI-naive stented patients treated with standard
      clopidogrel and aspirin therapy for at least six months (n=100). The patients
      were randomly assigned to receive either cilostazol at a dose of 100mg twice
      daily (CILO group) or clopidogrel at a dose of 75mg daily (CLPD group) in
      addition to lansoprazole (30mg daily). The platelet aggregation (PA) determined
      using light transmittance aggregometry and the platelet reactivity index (PRI)
      obtained using a vasodilator-stimulated phosphoprotein phosphorylation assay were
      measured before randomization and at the 14-day follow-up visit. The primary
      endpoint was the PRI value at follow-up. RESULTS: At follow-up, the CLPD group
      showed similar values of PRI as the CILO group (66.9+/-14.0% vs. 63.1+/-14.1%;
      mean difference: 3.9%; 95% confidence interval of difference: -1.7% to 9.4%;
      p=0.174). However, the 6MUg/mL collagen- and 0.5mg/mL arachidonic acid-induced PA
      values in the CLPD group were higher than those observed in the CILO group (mean
      differences: 9.8% to 11.1%; all p values <0.001). CYP2C19 loss-of-function allele
      carriage was the major contributing factor associated with the PRI level in the
      absence of lansoprazole treatment (with a gene-dose effect); this association was
      not observed in the subjects receiving lansoprazole co-administration in the CLPD
      group. CONCLUSIONS: During lansoprazole co-administration, cilostazol treatment
      achieves a more favorable platelet function profile than clopidogrel therapy. The
      use of combination treatment with cilostazol and aspirin deserves further
      attention with respect to the management of stable stented patients requiring PPI
      co-administration.

PMID- 24942408
TI  - A unique role for retrospective studies in clinical oncology.

PMID- 24942458
TI  - A high-yield two-step transfer printing method for large-scale fabrication of
      organic single-crystal devices on arbitrary substrates.
AB  - Single-crystal organic nanostructures show promising applications in flexible and
      stretchable electronics, while their applications are impeded by the large
      incompatibility with the well-developed photolithography techniques. Here we
      report a novel two-step transfer printing (TTP) method for the construction of
      organic nanowires (NWs) based devices onto arbitrary substrates. Copper
      phthalocyanine (CuPc) NWs are first transfer-printed from the growth substrate to
      the desired receiver substrate by contact-printing (CP) method, and then
      electrode arrays are transfer-printed onto the resulting receiver substrate by
      etching-assisted transfer printing (ETP) method. By utilizing a thin copper (Cu)
      layer as sacrificial layer, microelectrodes fabricated on it via photolithography
      could be readily transferred to diverse conventional or non-conventional
      substrates that are not easily accessible before with a high transfer yield of
      near 100%. The ETP method also exhibits an extremely high flexibility; various
      electrodes such as Au, Ti, and Al etc. can be transferred, and almost all types
      of organic devices, such as resistors, Schottky diodes, and field-effect
      transistors (FETs), can be constructed on planar or complex curvilinear
      substrates. Significantly, these devices can function properly and exhibit closed
      or even superior performance than the device counterparts fabricated by
      conventional approach. 

PMID- 24942460
TI  - Dihydrogen activation by a silylium silylene frustrated Lewis pair and the
      unexpected isomerization reaction of a protonated silylene.
AB  - The isolable silylene 1 forms a frustrated Lewis pair with silylium ion 2 that is
      able to split hydrogen under ambient conditions. The protonated silylene 3
      obtained in this reaction isomerizes to yield the hydrogen-bridged disilyl cation
      4. Cation 4 is fully characterized by NMR spectroscopy and by XRD analysis. Its
      formation via the protonated silylene 3 is indicated by independent synthesis of
      cation 3 by hydride abstraction from the corresponding dihydridosilane 11 and is
      further supported by the results of density functional calculations. 

PMID- 24942409
TI  - Differential impact of methylphenidate and atomoxetine on sustained attention in
      youth with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: This study examined the effects of atomoxetine (ATX) and OROS
      methylphenidate (MPH) on laboratory measures of inhibitory control and attention
      in youth with attention-deficit/hyperactivity disorder (ADHD). It was
      hypothesized that performance would be improved by both treatments, but response
      profiles would differ because the medications work via different mechanisms.
      METHODS: One hundred and two youth (77 male; mean age = 10.5 +/- 2.7 years) with
      ADHD received ATX (1.4 +/- 0.5 mg/kg) and MPH (52.4 +/- 16.6 mg) in a randomized,
      double-blind, crossover design. Medication was titrated in 4-6-week blocks
      separated by a 2-week placebo washout. Inhibitory control and attention measures
      were obtained at baseline, following washout, and at the end of each treatment
      using Conners' Continuous Performance Test II (CPT-II), which provided age
      adjusted T-scores for reaction time (RT), reaction time variability (RT
      variability), and errors. Repeated-measures analyses of variance were performed,
      with Time (premedication, postmedication) and Treatment type (ATX, MPH) entered
      as within-subject factors. Data from the two treatment blocks were checked for
      order effects and combined if order effects were not present. CLINICAL TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT00183391. RESULTS: Main effects for Time on
      RT (p = .03), RTSD (p = .001), and omission errors (p = .01) were significant. A
      significant Drug * Time interaction indicated that MPH improved RT, RTSD, and
      omission errors more than ATX (p < .05). Changes in performance with treatment
      did not correlate with changes in ADHD symptoms. CONCLUSIONS: MPH has greater
      effects than ATX on CPT measures of sustained attention in youth with ADHD.
      However, the dissociation of cognitive and behavioral change with treatment
      indicates that CPT measures cannot be considered proxies for symptomatic
      improvement. Further research on the dissociation of cognitive and behavioral
      endpoints for ADHD is indicated.

PMID- 24942459
TI  - Cross-species outlier detection reveals different evolutionary pressures between
      sister species.
AB  - Lodgepole pine (Pinus contorta var. latifolia) and jack pine (Pinus banksiana)
      hybridize in western Canada, an area of recent mountain pine beetle range
      expansion. Given the heterogeneity of the environment, and indications of local
      adaptation, there are many unknowns regarding the response of these forests to
      future outbreaks. To better understand this we aim to identify genetic regions
      that have adaptive potential. We used data collected on 472 single nucleotide
      polymorphism (SNP) loci from 576 tree samples collected across 13 lodgepole pine
      dominated sites and four jack pine-dominated sites. We looked at the relationship
      of genetic diversity with the environment, and we identified candidate loci using
      both frequency-based (arlequin and bayescan) and correlation-based (matsam and
      bayenv) methods. We found contrasting relationships between environmental
      variation and genetic diversity for the species. While we identified a number of
      candidate outliers (34 in lodgepole pine, 25 in jack pine, and 43 interspecific
      loci), we did not find any loci in common between lodgepole and jack pine. Many
      of the outlier loci identified were correlated with environmental variation.
      Using rigorous criteria we have been able to identify potential outlier SNPs. We
      have also found evidence of contrasting environmental adaptations between
      lodgepole and jack pine which could have implications for beetle spread risk. 

PMID- 24942461
TI  - Genome-wide analysis of the WRKY gene family in cotton.
AB  - WRKY proteins are major transcription factors involved in regulating plant growth
      and development. Although many studies have focused on the functional
      identification of WRKY genes, our knowledge concerning many areas of WRKY gene
      biology is limited. For example, in cotton, the phylogenetic characteristics,
      global expression patterns, molecular mechanisms regulating expression, and
      target genes/pathways of WRKY genes are poorly characterized. Therefore, in this
      study, we present a genome-wide analysis of the WRKY gene family in cotton
      (Gossypium raimondii and Gossypium hirsutum). We identified 116 WRKY genes in G.
      raimondii from the completed genome sequence, and we cloned 102 WRKY genes in G.
      hirsutum. Chromosomal location analysis indicated that WRKY genes in G. raimondii
      evolved mainly from segmental duplication followed by tandem amplifications.
      Phylogenetic analysis of alga, bryophyte, lycophyta, monocot and eudicot WRKY
      domains revealed family member expansion with increasing complexity of the plant
      body. Microarray, expression profiling and qRT-PCR data revealed that WRKY genes
      in G. hirsutum may regulate the development of fibers, anthers, tissues (roots,
      stems, leaves and embryos), and are involved in the response to stresses.
      Expression analysis showed that most group II and III GhWRKY genes are highly
      expressed under diverse stresses. Group I members, representing the ancestral
      form, seem to be insensitive to abiotic stress, with low expression divergence.
      Our results indicate that cotton WRKY genes might have evolved by adaptive
      duplication, leading to sensitivity to diverse stresses. This study provides
      fundamental information to inform further analysis and understanding of WRKY gene
      functions in cotton species. 

PMID- 24942462
TI  - Hexacyanoferrate-adapted biofilm enables the development of a microbial fuel cell
      biosensor to detect trace levels of assimilable organic carbon (AOC) in
      oxygenated seawater.
AB  - A marine microbial fuel cell (MFC) type biosensor was developed for the detection
      of assimilable organic carbon (AOC) in ocean water for the purpose of online
      water quality monitoring for seawater desalination plants prone to biofouling of
      reverse osmosis (RO) membranes. The anodophilic biofilm that developed on the
      graphite tissue anode could detect acetate as the model AOC to concentrations as
      low as 5 uM (120 ug/L of AOC), which is sufficiently sensitive as an online
      biofouling risk sensor. Although the sensor was operated at a higher (+200 +/- 10
      mV) than the usual (-300 mV) anodic potential, the presence of oxygen completely
      suppressed the electrical signal. In order to overcome this outcompeting effect
      of oxygen over the anode as electron acceptor by the bacteria, hexacyanoferrate
      (HCF(III)) was found to enable the development of an adapted biofilm that
      transferred electrons to HCF(III) rather than oxygen. As the resultant of the
      reduced HCF(II) could readily transfer electrons to the anode while being re
      oxidised to HCF(III), the marine MFC biosensor developed could be demonstrated to
      work in the presence of oxygen unlike traditional MFC. The possibility of
      operating the marine MFC in batch or continuous (in-line) mode has been explored
      by using coulombic or potentiometric interpretation of the signal.

PMID- 24942463
TI  - Concurrent intrathecal methotrexate and liposomal cytarabine for leptomeningeal
      metastasis from solid tumors: a retrospective cohort study.
AB  - Leptomeningeal metastasis (LM) from solid tumors is typically a late
      manifestation of systemic cancer with limited survival. Randomized trials
      comparing single agent intrathecal methotrexate to liposomal cytarabine have
      shown similar efficacy and tolerability. We hypothesized that combination
      intrathecal chemotherapy would be a safe and tolerable option in solid tumor LM.
      We conducted a retrospective cohort study of combination IT chemotherapy in solid
      tumor LM at a single institution between April 2010 and July 2012. In addition to
      therapies directed at active systemic disease, each subject received IT liposomal
      cytarabine plus IT methotrexate with dexamethasone premedication. Patient
      characteristics, survival outcomes and toxicities were determined by systematic
      chart review. Thirty subjects were treated during the study period. The most
      common cancer types were breast 15 (50 %), glioblastoma 6 (20 %), and lung 5 (17
      %). Cytologic clearance was achieved in 6 (33 %). Median non-glioblastoma overall
      survival was 30.2 weeks (n = 18; range 3.9-73.4), and did not differ
      significantly by tumor type. Median time to neurologic progression was 7 weeks (n
      = 8; range 0.9-57), with 10 subjects (56 %) experiencing death from systemic
      disease without progression of LM. Age less than 60 was associated with longer
      overall survival (p = 0.01). Six (21 %) experienced grade III toxicities during
      treatment, most commonly meningitis 2 (7 %). Combination IT chemotherapy was
      feasible in this small retrospective cohort. Prospective evaluation is necessary
      to determine tolerability, the impact on quality of life and neurocognitive
      outcomes or any survival benefit when compared to single agent IT chemotherapy.

PMID- 24942464
TI  - Relationship between genome and epigenome--challenges and requirements for future
      research.
AB  - Understanding the links between genetic, epigenetic and non-genetic factors
      throughout the lifespan and across generations and their role in disease
      susceptibility and disease progression offer entirely new avenues and solutions
      to major problems in our society. To overcome the numerous challenges, we have
      come up with nine major conclusions to set the vision for future policies and
      research agendas at the European level. 

PMID- 24942465
TI  - Entry and re-entry into informal care-giving over a 3-year prospective study
      among older people in Nairobi slums, Kenya.
AB  - This paper analyses data from a 3-year prospective study to understand the
      factors associated with becoming a caregiver to a person with a chronic illness
      and examines the dynamics among caregivers over time. A total of 1485
      participants were drawn from a study conducted in the slums of Nairobi, Kenya.
      Two waves of data collected in 2006 for the baseline and a follow-up in 2009 were
      used. Information on the demographic, self-reported health and socioeconomic
      characteristics such as education, sources of livelihood and employment status
      was used. Age was a significant factor in becoming a caregiver, but there were no
      significant differences by gender or marital status. New caregivers and those
      with more than one care-giving episode had a higher socioeconomic position than
      non-caregivers. Caregivers also had poorer health compared with non-caregivers,
      highlighting the association between being a caregiver and negative health
      outcomes. Additionally, having cared for someone with a HIV-related illness
      compared with other chronic conditions increased the likelihood of subsequently
      caring for another person in need of long-term care. This may be due to the
      heterosexual mode of HIV transmission in sub-Saharan Africa, hence clustering of
      infection within family or married couples. This finding draws attention to the
      need to provide timely interventions to caregivers for people with HIV-related
      illness who are likely to end up providing care to multiple care recipients.
      Furthermore, there is a need to enhance the indispensable contribution of
      informal caregivers through incorporating their role within the continuum of care
      for effective HIV and AIDS management. Overall, informal caregivers to persons
      with chronic illnesses perform the tasks of care-giving without any formal
      support from health or social services. Therefore, it is crucial to initiate
      policies and programmes to ease the burden of care that is borne by informal
      caregivers. 

PMID- 24942466
TI  - Use of oral and subcutaneous methotrexate in rheumatoid arthritis patients in the
      United States.
AB  - OBJECTIVE: To examine the patterns of methotrexate (MTX) use among rheumatoid
      arthritis (RA) patients. METHODS: Using data from RA patients enrolled in a US
      commercial health plan and the US Medicare program, we identified RA patients
      initiating oral MTX. Persistence with MTX (oral or subcutaneous [SC]) was defined
      as no gap for >=90 days. RESULTS: New oral MTX users in Medicare (n = 20,431)
      were 76.9% women, had a mean +/- SD age of 69.7 +/- 11.7 years, and contributed a
      median followup of 2.6 years (interquartile range 1.7-3.5 years). Only 38%
      received dosages >=20 mg/week at any time. Approximately 50% of patients
      discontinued MTX at 1 year, although more than one-third of patients subsequently
      restarted. New commercially insured oral MTX users (n = 4,048) were similar to
      Medicare patients, except for age. Among Medicare patients, 19% starting oral MTX
      subsequently initiated a biologic agent, mostly anti-tumor necrosis factor (85%).
      Of these, only 50% received MTX at a dosage of >=20 mg/week, and only 21% of
      individuals switched to SC MTX (4%) or received hydroxychloroquine (8%),
      sulfasalazine (5%), or leflunomide (8%) prior to biologic agents. In commercially
      insured patients, 35% initiated a biologic agent, mostly anti-tumor necrosis
      factor therapies (90%). Of these, 43% never received MTX >=20 mg/week.
      CONCLUSION: Titration to a higher-dose oral MTX and use of SC MTX among RA
      patients were infrequent and may have been underutilized. Further work to
      optimize MTX dosing before patients are switched to a biologic agent may be
      warranted.

PMID- 24942468
TI  - Micafungin is more active against Candida albicans biofilms with high metabolic
      activity.
AB  - BACKGROUND: The ability to form biofilm enables Candida spp. to cause catheter
      related candidaemia. The use of agents with in vitro activity against Candida
      albicans biofilms, such as micafungin, could obviate catheter removal. The
      metabolic activity of C. albicans biofilms is strain-dependent, and cell wall
      formation is thought to be more prominent in biofilms showing high metabolic
      activity. METHODS: We studied the antifungal activity of micafungin against 265
      C. albicans isolates with different degrees of metabolic activity causing
      fungaemia in 246 patients admitted to Gregorio Maranon Hospital (January 2007 to
      June 2013). All strains were classified according to the metabolic activity of
      their biofilm, which was classified as low, moderate and high using XTT.
      Micafungin MICs for planktonic and sessile cells were assessed using the EUCAST
      E.Def 7.2 procedure and XTT reduction assay, respectively. The MIC was defined as
      a 50% and 80% reduction in metabolic activity compared with the control well.
      RESULTS: Micafungin was uniformly more active against planktonic cells than
      against sessile cells (MIC50 <= 0.015 versus 8 mg/L), although it was not
      consistently active against all C. albicans biofilms. Isolates with low metabolic
      activity biofilms showed the lowest susceptibility to micafungin, followed by
      moderate and high metabolic activity biofilms (P < 0.001). CONCLUSIONS: Our study
      suggests that the metabolic activity of biofilm may have a role in future
      evaluations of micafungin for the eradication of C. albicans biofilms (e.g. the
      lock therapy approach).

PMID- 24942467
TI  - Differential effects of intermittent versus continuous haloperidol treatment
      throughout adolescence on haloperidol sensitization and social behavior in
      adulthood.
AB  - Animal work on the behavioral effects of antipsychotic treatment suggests that
      different dosing regimens could affect drug sensitivity differently, with an
      intermittent treatment regimen tending to cause a sensitization effect, while a
      continuous treatment causing a tolerance. In this study, we explored how
      haloperidol (HAL) sensitization induced throughout adolescence and tested in
      adulthood was differentially impacted by these two dosing regimens in the
      conditioned avoidance response (CAR) test. We also examined how these two dosing
      regiments affected social interaction and social memory in adulthood. Male
      adolescent Sprague-Dawley rats were treated with HAL via either osmotic minipump
      (HAL-0.25 CONT; 0.25 mgkg(-1)day(-1), n = 14) or daily injection (HAL-0.05 INT;
      0.05 mgkg(-1)day(-1) injection, sc, n = 14), or sterile water (n = 14) from
      postnatal days (PND) 44 to 71. HAL sensitization was assessed in a challenge test
      in which all rats were injected with HAL (0.025 and 0.05 mg/kg, sc) on PND 80 and
      PND 82. Two days later, half of the rats from each group (n = 7/group) were
      assayed in two 4-trial social interaction tests in which a subject rat was given
      four 5-min social encounters with a familiar or novel juvenile rat (PND 35-40) at
      10 min intervals. Another half were tested in a quinpirole-induced
      hyperlocomotion assay to assess the potential HAL-induced change in D2-mediated
      function. Results show that only the intermittent dosing group under the HAL 0.05
      mg/kg challenge showed a robust sensitization effect as rats in this group made
      significantly fewer avoidance responses than those in the vehicle and HAL-0.25
      CONT groups. Adolescent HAL treatment did not affect social behavior and social
      memory, as rats from all 3 groups exhibited a similar level of social interaction
      and showed a similar level of sensitivity to the change of social stimuli.
      Similarly, adolescent HAL treatment also did not produce a long-lasting change in
      D2 function, as all 3 groups exhibited a similar level of increase in motor
      activity under quinpirole challenge. These findings suggest that HAL
      sensitization is a dosing-specific phenomenon. It is more likely to be seen under
      an intermittent dosing regimen than under a continuous dosing one. The findings
      that the intermittent HAL treatment did not impair social functioning and did not
      alter D2 function suggest a dissociation between drug-induced alterations in drug
      sensitivity and those in social function and neuroreceptors. 

PMID- 24942469
TI  - An unusual synchronous ileosigmoid and ileoileal knotting: a case report.
AB  - INTRODUCTION: Ileosigmoid and ileoileal knotting are two rare entities. They
      usually present as acute abdomen and the diagnosis is established
      intraoperatively. The treatment is surgical and should be performed as soon as
      possible to decrease the incidence of perioperative mortality and morbidity. CASE
      PRESENTATION: We report an unusual case of a 26-year-old Argentine man with
      ischemic necrosis in parts of his small and large intestine due to combined
      ileosigmoid and ileoileal knotting. He had an ileal loop of ileum concurrently
      wrapped around the neck of a sigmoid volvulus and other loops of ileum
      strangulating them, forming two different tangles of tying. This very rare and
      unusual entity was diagnosed and managed intraoperatively during a diagnostic
      laparotomy performed on an emergency basis. Both the gangrenous small bowel loops
      and the affected sigmoid colon area were resected. The continuation of the
      intestinal tract was restored by primary end-to-end anastomoses. The present case
      is unusual and to the best of our knowledge no similar cases of simultaneous
      ileosigmoid and ileoileal knotting have been described in the literature. The
      postoperative course of our patient was uneventful and he was discharged from the
      hospital on the 15th postoperative day. One year later he still remains without
      symptoms from his intestinal tract. CONCLUSION: Simultaneous ileosigmoid and
      ileoileal knotting is a very rare entity that should be diagnosed and treated
      surgically on an emergency basis to minimize the high postoperative morbidity and
      mortality.

PMID- 24942471
TI  - Temperature-responsive telechelic dipalmitoylglyceryl poly(N-isopropylacrylamide)
      vesicles: real-time morphology observation in aqueous suspension and in the
      presence of giant liposomes.
AB  - Telechelic alpha,omega-di(twin-tailed poly(N-isopropylacrylamides)) form
      polymersomes in water that increase in size by fusion when the water temperature
      exceeds the polymers cloud point temperature. Hybrid vesicles form in mixed
      suspensions of giant phospholipid liposomes and polymersomes by
      adsorption/fusion, and undergo further transformations, such as fission. 

PMID- 24942470
TI  - Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous
      pericarditis compared to adenosine deaminase and unstimulated interferon-gamma in
      a high burden setting: a prospective study.
AB  - BACKGROUND: Tuberculous pericarditis (TBP) is associated with high morbidity and
      mortality, and is an important treatable cause of heart failure in developing
      countries. Tuberculous aetiology of pericarditis is difficult to diagnose
      promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the
      diagnosis of TBP is unknown. This study sought to evaluate the diagnostic
      accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase
      (ADA) and unstimulated interferon-gamma (uIFNgamma) in suspected TBP. METHODS:
      From October 2009 through September 2012, 151 consecutive patients with suspected
      TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium
      tuberculosis culture and/or pericardial histology served as the reference
      standard for definite TBP. Receiver-operating-characteristic curve analysis was
      used for selection of ADA and uIFNgamma cut-points. RESULTS: Of the participants,
      49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and
      18% (27/151) as non TBP. A total of 105 (74%) participants were human
      immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and
      specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100%
      (85.6% to 100%), respectively. Concentration of pericardial fluid by
      centrifugation and using standard sample processing did not improve Xpert MTB/RIF
      accuracy. ADA (>=35 IU/L) and uIFNgamma (>=44 pg/ml) both had a sensitivity of
      95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10).
      However, the specificity and positive likelihood ratio of uIFNgamma was higher
      than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to
      93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of
      TB of 30%. The sensitivity and negative predictive value of both uIFNgamma and
      ADA were higher than Xpert-MT/RIF (P < 0.001). CONCLUSIONS: uIFNgamma offers
      superior accuracy for the diagnosis of microbiologically confirmed TBP compared
      to the ADA assay and the Xpert MTB/RIF test.

PMID- 24942472
TI  - The genetic basis for inactivation of Wnt pathway in human osteosarcoma.
AB  - BACKGROUND: Osteosarcoma is a highly genetically unstable tumor with poor
      prognosis. We performed microarray-based comparative genomic hybridization
      (aCGH), transcriptome sequencing (RNA-seq), and pathway analysis to gain a
      systemic view of the pathway alterations of osteosarcoma. METHODS: aCGH
      experiments were carried out on 10 fresh osteosarcoma samples. The output data
      (Gene Expression Omnibus Series accession number GSE19180) were pooled with
      published aCGH raw data (GSE9654) to determine recurrent copy number changes.
      These were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
      analysis to identify altered pathways in osteosarcoma. Transcriptome sequencing
      of six osteosarcomas was performed to detect the expression profile of Wnt
      signaling pathway genes. Protein expression of WNT1, beta-catenin, c-myc, and
      cyclin D1 in the Wnt pathway was detected by immunohistochemistry (IHC) in an
      independent group of 46 osteosarcoma samples. RESULTS: KEGG pathway analysis
      identified frequent deletions of Wnt and other Wnt signaling pathway genes. At
      the mRNA level, transcriptome sequencing found reduced levels of mRNA expression
      of Wnt signaling pathway transcripts. While WNT1 protein expression was detected
      by IHC in 69.6% (32/46) of the osteosarcomas, no beta-catenin protein was
      detected in the nucleus. beta-catenin protein expression was, however, detected
      in the membrane and cytoplasm of 69.6% (32/46) of the osteosarcomas. c-myc
      protein expression was detected in only 47.8% (22/46) and cyclin D1 protein
      expression in 52.2% (24/46) of osteosarcoma samples. Kaplan-Meier survival
      analysis showed that WNT1-negative patients had a trend towards longer disease
      free survival than WNT1-positive patients. Interestingly, in WNT1-negative
      patients, those who were also cyclin D1-negative had significantly longer disease
      free survival than cyclin D1-positive patients. However, there was no significant
      association between any of the investigated proteins and overall survival of
      human osteosarcoma patients. CONCLUSIONS: Frequent deletions of Wnt and other Wnt
      signaling pathway genes suggest that the Wnt signaling pathway is genetically
      inactivated in human osteosarcoma.

PMID- 24942476
TI  - Ensuring a proactive, evidence-based, patient safety approach to patient
      assessment.
AB  - AIMS AND OBJECTIVES: To argue that if all nurses were to adopt the primary survey
      approach (assessment of airway, breathing, circulation and disability) as the
      first element of patient assessment, they would be more focused on active
      detection of clinical deterioration rather than passive collection of patient
      data. BACKGROUND: Nurses are the professional group that carry the highest level
      of responsibility for patient assessment, accurate data collection and
      interpretation. The timely recognition of, and response to deteriorating
      patients, is dependent on the measurement and interpretation of pertinent
      physiological data by nurses. DESIGN: Discursive paper. METHODS: Traditionally
      taught and commonly used approaches to patient assessment such as 'vital signs'
      and 'body systems' are not evidence-based nor framed in patient safety. The
      primary survey approach as the first element in patient assessment has three
      major advantages: (1) data are collected according to clinical importance; (2)
      data are collected using the same framework as most organisation's rapid response
      system activation criteria; and (3) the primary survey acts as a patient safety
      checklist, thereby decreasing the risk of failure to recognise, and therefore
      respond to, deteriorating patients. CONCLUSION: The vital signs and body systems
      approaches to patient assessment have significant limitations in identifying
      clinical deterioration. The primary survey approach provides nurses with a
      consistent, evidence-based and sequenced approach to patient assessment in every
      clinical setting. RELEVANCE TO CLINICAL PRACTICE: All nurses should use a primary
      survey approach as the first element of patient assessment in every patient
      encounter as a patient safety strategy.

PMID- 24942474
TI  - Salt stress-induced alterations in the root proteome of Amaranthus cruentus L.
AB  - Salt stress is one of the major factors limiting crop productivity worldwide.
      Amaranth is a highly nutritious pseudocereal with remarkable nutraceutical
      properties; it is also a stress-tolerant plant, making it an alternative crop for
      sustainable food production in semiarid conditions. A two-dimensional
      electrophoresis gel coupled with a liquid chromatography-mass spectrometry/mass
      spectrometry (LC-MS/MS) approach was applied in order to analyze the changes in
      amaranth root protein accumulation in plants subjected to salt stress under
      hydroponic conditions during the osmotic phase (1 h), after recovery (24 h), and
      during the ionic phase of salt stress (168 h). A total of 101 protein spots were
      differentially accumulated in response to stress, in which 77 were successfully
      identified by LC-MS/MS and a database search against public and amaranth
      transcriptome databases. The resulting proteins were grouped into different
      categories of biological processes according to Gene Ontology. The identification
      of several protein isoforms with a change in pI and/or molecular weight reveals
      the importance of the salt-stress-induced posttranslational modifications in
      stress tolerance. Interestingly stress-responsive proteins unique to amaranth,
      for example, Ah24, were identified. Amaranth is a stress-tolerant alternative
      crop for sustainable food production, and the understanding of amaranth's stress
      tolerance mechanisms will provide valuable input to improve stress tolerance of
      other crop plants. 

PMID- 24942477
TI  - Molecular imaging in acromegaly: should clinicians look carefully at developments
      in the field?

PMID- 24942473
TI  - Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the
      Basilar Artery International Cooperation Study.
AB  - BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT
      Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the
      functional outcome of patients in the Basilar Artery International Cooperation
      Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS
      applied to perfusion CT (CTP) in the BASICS registry population. METHODS: We
      applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume
      (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and
      CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or
      CBF, or relative increase in MTT were rated as abnormal. RESULTS: CTA and CTP
      were available in 27/592 BASICS patients (4.6%). The proportion of patients with
      any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI],
      76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for
      CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23
      patients with a CBV pc-ASPECTS >= 8 had died at 1 month (RR 3.8; 95% CI, 1.9
      7.6). CONCLUSION: CTP was performed in a minority of the BASICS registry
      population. Perfusion disturbances in the posterior circulation were most
      pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with
      high case fatality.

PMID- 24942479
TI  - Do people who consciously attend to their movements have more self-reported knee
      pain? An exploratory cross-sectional study.
AB  - OBJECTIVES: This study explored the relationship between propensity for conscious
      control of movement (assessed by the Movement-Specific Reinvestment Scale) and
      self-reported knee pain. DESIGN: Cross-sectional study. SETTING: General
      population. SUBJECTS: Adults aged 18 to 55 years of age. MEASURES: Participants
      completed the movement-specific reinvestment scale and a self-report
      questionnaire on knee pain at the same time on one occasion. RESULTS: Data was
      collected on 101 adults of whom 34 (33.7%) self-reported knee pain. Mean scores
      on the conscious motor processing subscale of the movement-specific reinvestment
      scale, but not the movement self-consciousness subscale, were significantly
      higher for participants who reported knee pain within the previous year compared
      with those who did not (mean difference 3.03; t-test 2.66, df = 97, P = 0.009;
      95% confidence interval (CI) 0.77 to 5.30). The association between self-reported
      knee pain and propensity for conscious motor processing was still observed, even
      after controlling for movement self-consciousness subscale scores, age, gender
      and body mass index (adjusted odds ratio 1.16, 95% CI 1.04 to 1.30). CONCLUSIONS:
      Propensity for conscious control of movement may play a role in knee pain.

PMID- 24942478
TI  - Motivational interviewing to increase physical activity in people with chronic
      health conditions: a systematic review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis of randomized controlled trials
      to determine if motivational interviewing leads to increased physical activity,
      cardiorespiratory fitness or functional exercise capacity in people with chronic
      health conditions. DATA SOURCES: Seven electronic databases (MEDLINE, PsychINFO,
      EMBASE, AMED, CINHAL, SPORTDiscus and the Cochrane Central Register of Controlled
      trials) were searched from inception until January 2014. TRIAL SELECTION: Two
      reviewers independently examined publications for inclusion. Trials were included
      if participants were adults (>18 years), had a chronic health condition, used
      motivational interviewing as the intervention and examined physical activity,
      cardiorespiratory fitness or functional exercise capacity. DATA EXTRACTION: Two
      reviewers independently extracted data. Risk of bias within trials was assessed
      using the Physiotherapy Evidence Database Scale. DATA SYNTHESIS: Meta-analyses
      were conducted with standardized mean differences and 95% confidence intervals
      (CIs) were calculated. The Grades of Recommendation, Assessment, Development and
      Evaluation approach was used to evaluate the quality of the evidence. RESULTS:
      Eleven publications (of ten trials) were included. There was moderate level
      evidence that motivational interviewing had a small effect in increasing physical
      activity levels in people with chronic health conditions relative to comparison
      groups (standardized mean differences = 0.19, 95% CI 0.06 to 0.32, p = 0.004).
      Sensitivity analysis based on trials that confirmed treatment fidelity produced a
      larger effect. No conclusive evidence was observed for cardiorespiratory fitness
      or functional exercise capacity. CONCLUSION: The addition of motivational
      interviewing to usual care may lead to modest improvements in physical activity
      for people with chronic health conditions.

PMID- 24942480
TI  - Rehabilitation for post-stroke cognitive impairment: an overview of
      recommendations arising from systematic reviews of current evidence.
AB  - BACKGROUND: Although cognitive impairments are common following stroke, there is
      considerable uncertainty about the types of interventions that can reduce
      activity restrictions and improve quality of life. Indeed, a recent project to
      identify priorities for research into life after stroke determined that the top
      priority for patients, carers and health professionals was how to improve
      cognitive impairments. OBJECTIVE: To provide an overview of the evidence for the
      effectiveness of cognitive rehabilitation for patients with stroke and to
      determine the main gaps in the current evidence base. METHODS: Evidence was
      synthesised for the six Cochrane reviews relating to rehabilitation for post
      stroke cognitive impairment and any subsequently published randomized controlled
      trials to February 2012. RESULTS: Data arising from 44 trials involving over 1500
      patients was identified. Though there was support for the effectiveness of
      cognitive rehabilitation for some cognitive impairments, significant gaps were
      found in the current evidence base. All of the Cochrane reviews identified major
      limitations within the evidence they identified. CONCLUSIONS: There is currently
      insufficient research evidence, or evidence of insufficient quality, to support
      clear recommendations for clinical practice. Recommendations are made as to the
      research required to strengthen the evidence base, and so facilitate the delivery
      of effective interventions to individuals with cognitive impairment after stroke.

PMID- 24942481
TI  - Cost analysis of the Communication and Low Mood (CALM) randomised trial of
      behavioural therapy for stroke patients with aphasia.
AB  - OBJECTIVE: To evaluate the cost effectiveness of a behavioural therapy
      intervention shown to be clinically effective in comparison with usual care for
      stroke patients with aphasia. DESIGN: Randomised controlled trial with comparison
      of costs and calculation of incremental cost effectiveness ratio. SETTING:
      Community. PARTICIPANTS: Participants identified as having low mood on either the
      Visual Analog Mood Scale sad item (>=50) or Stroke Aphasic Depression
      Questionnaire Hospital version 21 (SADQH21) (>=6) were recruited. INTERVENTIONS:
      Participants were randomly allocated to behavioural therapy or usual care using
      internet-based randomisation generated in advance of the study by a clinical
      trials unit. MAIN MEASURES: Outcomes were assessed at six months after
      randomisation, blind to group allocation. The costs were assessed from a service
      use questionnaire. Effectiveness was defined as the change in SADQH21 scores and
      a cost-effectiveness analysis was performed comparing the behavioural group with
      the usual care control group. The cost analysis was undertaken from the
      perspective of the UK NHS and Social Services. RESULTS: The greatest difference
      was in home help costs where there was a saving of L56.20 in the intervention
      group compared to an increase of L61.40 in the control group. At six months the
      SADQH21 score for the intervention group was 17.3 compared to the control group
      value of 20.4. This resulted in a mean increase of 0.7 in the control group,
      compared to a mean significant different decrease of 6 in the intervention group
      (P = 0.003). The Incremental Cost-Effectiveness Ratio indicated that the cost per
      point reduction on the SADQH21 was L263. CONCLUSION: Overall the behavioural
      therapy was found to improve mood and resulted in some encouraging savings in
      resource utilisation over the six months follow-up.

PMID- 24942482
TI  - Ester hydrolysis of polysorbate 80 in mAb drug product: evidence in support of
      the hypothesized risk after the observation of visible particulate in mAb
      formulations.
AB  - An observation of visible particulate matter was made during formulation
      development of a mAb and investigations initiated to understand the colloidal
      instability of the formulation. It was observed that there was a loss of
      polysorbate in the IgG formulation and concurrent hydrolysis of polysorbate 80
      (PS80) into fatty acid, polyethylene glycol (PEG), and pegylated sorbitan in the
      presence of mAb A. This observation was confirmed with two other mAb development
      programs (mAb B and mAb C) that used PS80 and formed particulate, but was absent
      in any placebo sample tested. Comparative analysis to acid, base and esterase
      hydrolysis, and exposure to the oxidation reagents Iron(II) and tert-Butyl
      hydroperoxide demonstrates that the observed reaction is reproduced by a biologic
      (enzymatic) mechanism. Monooleates of PS80, including the sorbitan and PEG
      oleates, are hydrolyzed first, showing a slower reaction with higher-order
      oleates. This leads to a change in the composition of the formulation over time
      where PS85 becomes the predominant component of the original surfactant remaining
      in solution. Data suggest that there is a lipid-specific mechanism rather than a
      general biologic hydrolysis mechanism that hydrolyzes oleate esters of PS80
      increasing the risk that colloidal IgG particles will form in mAb drug product.

PMID- 24942483
TI  - Inertial sensor real-time feedback enhances the learning of cervical spine
      manipulation: a prospective study.
AB  - BACKGROUND: Cervical Spinal Manipulation (CSM) is considered a high-level skill
      of the central nervous system because it requires bimanual coordinated rhythmical
      movements therefore necessitating training to achieve proficiency. The objective
      of the present study was to investigate the effect of real-time feedback on the
      performance of CSM. METHODS: Six postgraduate physiotherapy students attending a
      training workshop on Cervical Spine Manipulation Technique (CSMT) using inertial
      sensor derived real-time feedback participated in this study. The key variables
      were pre-manipulative position, angular displacement of the thrust and angular
      velocity of the thrust. Differences between variables before and after training
      were investigated using t-tests. RESULTS: There were no significant differences
      after training for the pre-manipulative position (rotation p = 0.549; side
      bending p = 0.312) or for thrust displacement (rotation p = 0.247; side bending p
      = 0.314). Thrust angular velocity demonstrated a significant difference following
      training for rotation (pre-training mean (sd) 48.9 degrees /s (35.1); post
      training mean (sd) 96.9 degrees /s (53.9); p = 0.027) but not for side bending (p
      = 0.521). CONCLUSION: Real-time feedback using an inertial sensor may be valuable
      in the development of specific manipulative skill. Future studies investigating
      manipulation could consider a randomized controlled trial using inertial sensor
      real time feedback compared to traditional training.

PMID- 24942484
TI  - Acute ethanol alters multiple histone modifications at model gene promoters in
      the cerebral cortex.
AB  - BACKGROUND: Ethanol (EtOH) exposure alters gene expression in the cerebral cortex
      (CCx); however, mechanisms of EtOH-induced gene regulation are not well
      understood. We hypothesized that EtOH regulates gene expression by differentially
      altering histone modifications at gene promoters that are up- and down-regulated
      by EtOH. Such epigenetic mechanisms may ultimately contribute to EtOH-induced
      neuro-adaptations that underlie tolerance, dependence, and EtOH-use disorders.
      METHODS: Eight-week-old, male C57BL/6J mice were treated with 3 g/kg EtOH
      (intraperitoneally) or saline and sacrificed 6 hours after injection; the CCx and
      hippocampus (HC) were immediately removed and flash frozen. Chromatin
      immunoprecipitation was used to study the association of model gene promoters
      with histone modifications. Western blot was used to detect global changes in the
      histone modifications studied. We also used a polymerase chain reaction (PCR)
      array to identify changes in expression of chromatin-modifying enzymes. RESULTS:
      In CCx, acute EtOH decreased expression of Gad1, Hdac2, and Hdac11, which was
      associated with decreased histone acetylation at the Gad1 and Hdac2 promoters; we
      also identified increased expression of Mt1, Mt2, Egr1, which was associated with
      increased H3K4me3 levels at the Mt2 promoter and decreased H3K27me3 levels at the
      Mt1 promoter. We identified an increase in global levels of H3K4me3 in CCx as
      well as a global increase in H3K9ac and H3K14ac in HC. The PCR array identified
      decreased expression of Csrp2 bp, Hdac2, and Hdac11 as well as increased
      expression of Kat2b in CCx. CONCLUSIONS: Acute EtOH induces chromatin remodeling
      at model up- and down-regulated genes in CCx. Different patterns of histone
      modifications at these gene promoters indicate that EtOH may be acting through
      multiple histone-modifying enzymes to alter gene expression; in particular,
      differential expression of Kat2b, Hdac2, Hdac11, and Csrp2 bp in CCx may mediate
      EtOH-induced chromatin remodeling. Additional studies are necessary to determine
      the relationship between EtOH-induced changes in histone-modifying enzymes,
      specific EtOH-induced histone modifications, and gene expression.

PMID- 24942485
TI  - Do working conditions explain the increased risks of disability pension among men
      and women with low education? A follow-up of Swedish cohorts.
AB  - OBJECTIVES: Rates of disability pension are greatly increased among people with
      low education. This study examines the extent to which associations between
      education and disability pensions might be explained by differences in working
      conditions. Information on individuals at age 13 years was used to assess
      confounding of associations. METHOD: Two nationally representative samples of men
      and women born in 1948 and 1953 in Sweden (22 889 participants in total) were
      linked to information from social insurance records on cause (musculoskeletal,
      psychiatric, and other) and date (from 1986-2008) of disability pension.
      Education data were obtained from administrative records. Occupation data were
      used for measurement of physical strain at work and job control. Data on paternal
      education, ambition to study, and intellectual performance were collected in
      school. RESULTS: Women were found to have higher rates of disability pension than
      men, regardless of diagnosis, whereas men had a steeper increase in disability
      pension by declining educational level. Adjustment of associations for paternal
      education, ambition to study, and intellectual performance at age 13 had a
      considerable attenuating effect, also when disability pension with a
      musculoskeletal diagnosis was the outcome. Despite this, high physical strain at
      work and low job control both contributed to explain the associations between low
      education and disability pensions in multivariable models. CONCLUSION: Working
      conditions seem to partly explain the increased rate of disability pension among
      men and women with lower education even though this association does reflect
      considerable selection effects based on factors already present in late
      childhood.

PMID- 24942486
TI  - Role of 9p21 and 2q36 variants and arterial stiffness in the prediction of
      coronary artery disease.
AB  - BACKGROUND: Genetic polymorphisms and arterial stiffness indices have been
      associated with cardiovascular prognosis and the presence and extent of
      angiographic coronary artery disease (CAD). We aimed to investigate whether
      arterial stiffness indices and 9p21 and 2q36 variants may improve prediction of
      CAD presence and extent when added to classical cardiovascular risk factors in
      patients at high risk for CAD. MATERIALS AND METHODS: In this cross-sectional
      study, we enrolled 183 consecutive patients with suspected stable CAD (age 61 +/-
      9 years, 134 males) referred for diagnostic coronary angiography. Framingham risk
      score (FRS) was calculated. Arterial stiffness was assessed by carotid-femoral
      pulse wave velocity (PWV) and central augmentation index (AIx) using applanation
      tonometry. Genetic polymorphisms of 9p21 (rs1333049) and 2q36 (rs2943634) loci
      were also analysed. RESULTS: Higher FRS and PWV and the presence of rs2943634
      risk allele were independent predictors of CAD (Nagelkerke R(2) 0.252, P <
      0.001), while higher FRS and the presence of rs1333049 risk allele were
      independent predictors of multivessel CAD (Nagelkerke R(2) 0.190, P < 0.001).
      Genetic polymorphisms and vascular indices did not improve the predictive
      accuracy of FRS-based models (P > 0.1 for all) for CAD presence or extent.
      CONCLUSIONS: In these high-risk patients, 9p21 and 2q36 variants and PWV were
      independently associated with CAD presence and extent, but the addition of both
      genetic data and arterial stiffness indices to FRS did not improve the prediction
      of CAD compared with FRS alone. Further studies are needed to clarify the
      prognostic role of genetic and vascular indices in the prediction of angiographic
      CAD.

PMID- 24942487
TI  - Transparent-conducting-oxide nanowire arrays for efficient photoelectrochemical
      energy conversion.
AB  - We report one dimensional (1-D) transparent-conducting-oxide arrays coated with
      light-absorbing semiconductors to simultaneously maximize light harvesting and
      charge collection in a photoelectrochemical (PEC) system. Tin-doped indium oxide
      (ITO) nanowire (NW) arrays are prepared on ITO thin-film substrates as the
      transparent-conducting-oxide, and TiO2 or CdSe/CdS/TiO2 thin layers were coated
      on the ITO NW arrays as the solar light-absorbing layers. The optimal PEC
      performance, 0.85% under 100 mW cm(-2) of light illumination, is obtained from ~
      30 MUm-long ITO NW, which is covered with ~ 20 nm-thick TiO2 nanoshell. We
      finally demonstrate that the ITO NW-based photoelectrode is also compatible with
      one of the most efficient visible-light sensitizers, the CdS/CdSe quantum dot.
      Our approach using the transparent conducting 1-D array has wide potential to
      improve the PEC performances of conventional semiconducting materials through
      liberation from the poor charge transport.

PMID- 24942488
TI  - Role of organic osmolytes in water homoeostasis in skin.
AB  - The ability to conserve water is fundamental to terrestrial life. A number of
      organs such as the kidney and the bladder have important roles in the regulation
      of body water balance. The epidermis of skin is also fundamental to this process,
      and it is in a constant battle to prevent loss of water to the external, dry
      environment. Given this important role of the epidermis as a barrier to water
      loss, it is perhaps surprising that many of the cellular mechanisms by which
      human keratinocytes achieve cell volume homoeostasis, maintain epidermal
      hydration and adapt to biological effects from environmental stressors such as
      ultraviolet radiation are poorly understood. This article reviews what is known
      thus far and speculates about other potential mechanisms through which skin
      conducts water homoeostasis, with a particular emphasis on the putative role of
      organic osmolytes. 

PMID- 24942489
TI  - Experimental simulation of closed timelike curves.
AB  - Closed timelike curves are among the most controversial features of modern
      physics. As legitimate solutions to Einstein's field equations, they allow for
      time travel, which instinctively seems paradoxical. However, in the quantum
      regime these paradoxes can be resolved, leaving closed timelike curves consistent
      with relativity. The study of these systems therefore provides valuable insight
      into nonlinearities and the emergence of causal structures in quantum mechanics-
      essential for any formulation of a quantum theory of gravity. Here we
      experimentally simulate the nonlinear behaviour of a qubit interacting unitarily
      with an older version of itself, addressing some of the fascinating effects that
      arise in systems traversing a closed timelike curve. These include perfect
      discrimination of non-orthogonal states and, most intriguingly, the ability to
      distinguish nominally equivalent ways of preparing pure quantum states. Finally,
      we examine the dependence of these effects on the initial qubit state, the form
      of the unitary interaction and the influence of decoherence.

PMID- 24942490
TI  - ALK fusion and its association with other driver gene mutations in Finnish non
      small cell lung cancer patients.
AB  - Screening of anaplastic lymphoma tyrosine kinase (ALK) gene fusions in non-small
      cell lung cancer (NSCLC) patients enables the identification of the patients
      likely to benefit from ALK-targeted therapy. Our aim was to assess the prevalence
      of ALK fusion in Finnish NSCLC patients, which has not been reported earlier, and
      to study the presence of ALK fusion in relation to clinicopathological
      characteristics and other driver gene mutations. A total of 469 formalin-fixed
      paraffin-embedded tumor tissue specimens from Finnish NSCLC patients were
      screened for ALK fusion by immunohistochemistry (IHC). For confirmation of IHC
      results, fluorescence in situ hybridization (FISH) was conducted for 171
      specimens. Next-generation sequencing was performed for all ALK-positive
      specimens to characterize the association of ALK fusion with mutations in
      targeted regions of 22 driver genes. Of the 469 tumors screened, 11 (2.3%)
      harbored an ALK fusion, including nine adenocarcinomas and two large cell
      carcinomas. The IHC results for all 11 ALK-positive and 160 random ALK-negative
      specimens were confirmed by FISH. ALK fusion was significantly associated with
      never/ex-light smoking history (P<0.001) and younger age (P=0.004). Seven ALK
      positive tumors showed additional mutations; three in MET, one in MET and CTNNB1,
      two in TP53, and one in PIK3CA. Our results show that ALK fusion is an infrequent
      alteration in Finnish NSCLC patients. Although the majority of ALK-positive cases
      were adenocarcinomas, the fusion was also seen in large cell carcinomas. Further
      studies are needed to elucidate the clinical significance of the coexistence of
      ALK fusion with MET, TP53, CTNNB1, and PIK3CA mutations.

PMID- 24942491
TI  - Reliability and concurrent validity of knee angle measurement: smart phone app
      versus universal goniometer used by experienced and novice clinicians.
AB  - The use of goniometers to measure joint angles is a key part of musculoskeletal
      practice. Recently smartphone goniometry applications have become available to
      clinicians. This study examined the intra- and inter-measurer reliability of
      novice and experienced clinicians and the concurrent validity of assessing knee
      range of motion using a smartphone application (the Knee Goniometer App
      (Ockendon((c)))) (KGA) and a standard universal goniometer (UG). Three
      clinicians, each with over seven years' experience as musculoskeletal
      physiotherapists and three final year physiotherapy students, measured 18
      different knee joint angles three times, using both the universal goniometer and
      the smartphone goniometric application. The universal goniometer and the
      smartphone goniometric application were reliable in repeated measures of knee
      flexion angles (average Concordance Correlation Coefficient (CCC) > 0.98) with
      both experienced clinicians and final year physiotherapy students (average CCCs >
      0.96). There were no significant differences in reliability between the
      experienced and the novice practitioners for either device. Agreement between the
      universal goniometer and smartphone goniometric application measurements was also
      high for all examiners with average CCCs all above 0.96. The Standard Error of
      Measurement ranged between 1.56 degrees  (0.52-2.66) for the UG and 0.62 degrees 
      (0.29-1.27) for the KGA. The universal goniometer and the smartphone goniometric
      application were reliable in repeated measures of knee flexion angles. Smaller
      error of measurement values for the smartphone goniometric application might
      indicate superiority for assessment where clinical situations demand greater
      precision of knee range of motion. 

PMID- 24942492
TI  - Participation of the neutrophin brain-derived neurotrophic factor in
      neuropsychiatric systemic lupus erythematosus.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is associated with the
      pathogenesis of several neuropsychiatric (NP) diseases, but there are few studies
      involving SLE. The aim of this study was to investigate whether plasma BDNF
      levels are associated with disease activity in SLE patients with severe NPSLE and
      non-NPSLE manifestations. METHODS: We assessed 131 SLE patients and 24 randomly
      selected healthy individuals. SLE patients were evaluated in a cross-sectional
      study allocated according to the presence or not of NP manifestations and disease
      activity: (i) active NPSLE (n = 40), (ii) inactive NPSLE (n = 26), (iii) active
      SLE (n = 29) and (iv) inactive SLE (n = 36). In addition, NPSLE patients (n = 40)
      were evaluated before and after treatment. Disease activity was assessed
      according to the SLEDAI score. The plasma BDNF was measured by ELISA. RESULTS:
      BDNF levels were increased in inactive NPSLE when compared with active SLE and
      controls (P < 0.0001). We observed similar findings in inactive SLE when compared
      with active SLE (P < 0.0001). In addition, we found an inverse correlation
      between plasma BDNF levels and the SLEDAI (r = -0.54, P < 0.0001) and a positive
      correlation with complement levels. We also observed an increase in BDNF levels
      in parallel with the improvement in NP symptoms. CONCLUSION: Plasma BDNF level is
      increased in SLE patients and this increase is independent of the occurrence of
      NP manifestations. In addition, plasma BDNF levels increased with control of SLE
      activity, which points to the potential use of BDNF as a biomarker of response to
      treatment.

PMID- 24942494
TI  - "Ca(2+) signaling and cell death": the ECS 2013 workshop in Leuven and a tribute
      to Humbert De Smedt.

PMID- 24942493
TI  - Interferon-alpha-induced B-lymphocyte stimulator expression and mobilization in
      healthy and systemic lupus erthymatosus monocytes.
AB  - OBJECTIVE: The aim of this study was to investigate the cellular populations and
      regulatory factors responsible for B-lymphocyte stimulator (BLyS) overexpression
      in SLE patients. METHODS: Surface and intracellular BLyS levels were quantified
      by flow cytometry in healthy and SLE monocytes cultured in the presence of TNF
      alpha, IFN-alpha, IFN-gamma, GM-CSF and SLE immune complexes (SLE-ICs), while
      soluble BLyS was measured by ELISA. Also, both surface and intracellular BLyS
      expression by different cell subsets was determined in 23 SLE patients and 16
      healthy controls. Disease activity was assessed using classic BILAG index.
      RESULTS: In vitro experiments using healthy monocytes showed that IFN-alpha and
      SLE-ICs induced a progressive increase in surface-bound BLyS with respect to the
      intracellular stores. IFN-alpha-treated SLE monocytes, especially from patients
      with high anti-dsDNA levels or disease activity, exhibited higher intracellular
      levels of BLyS that was mobilized to the membrane more rapidly and subsequently
      released. Furthermore, ex vivo analysis of SLE patients revealed up-regulated
      BLyS expression in B cells, myeloid and plasmacytoid dendritic cells (DCs),
      whereas active patients had an increased surface:intracellular BLyS ratio in
      monocytes and myeloid DCs. CONCLUSION: Monocyte BLyS induction and mobilization
      from intra- to extracellular compartments seems to be influenced by IFN-alpha and
      disease activity or anti-dsDNA levels. Accordingly, monocytes and myeloid DCs
      from active patients presented the highest membrane-bound:intracellular BLyS
      ratio. In addition, expression levels in several blood cells support the
      existence of generalized immune stimulation in SLE patients.

PMID- 24942496
TI  - Consciousness without cortex: a hydranencephaly family survey.
AB  - AIM: Hydranencephaly is commonly taken to exemplify the developmental vegetative
      state, based largely on the assumption that radical loss of cortical tissue is
      incompatible with consciousness. The aim of the study reported here was to survey
      primary caregivers of children born with hydranencephaly for behavioural evidence
      indirectly informative about the conscious status of these children. METHODS: The
      survey recruited 108 primary caregivers through a parent support group and was
      conducted online via a commercial survey hosting facility. As part of a more
      extensive questionnaire, participants answered 106 questions bearing on the
      environmental responsiveness, emotional reactivity, mood and agency of the child
      in their care. RESULTS: The survey elicited a many-facetted and detailed set of
      caregiver answers and written observations regarding the child's behaviour. A
      conservative measure of agreement among respondents' answers yielded a generic
      portrait of the responsiveness and expressive behaviour of a hydranencephaly
      child. CONCLUSION: The generic behavioural characteristics of hydranencephaly
      thus assessed are incompatible on multiple counts with the unconsciousness
      characteristic of the vegetative state. This bears on what is included under the
      concept of quality of life for children with hydranencephaly, and hence on
      appropriate forms of treatment and care in their case.

PMID- 24942495
TI  - No association of atherosclerosis with digital ulcers in Japanese patients with
      systemic sclerosis: evaluation of carotid intima-media thickness and plaque
      characteristics.
AB  - Patients with systemic sclerosis (SSc) usually develop Raynaud's phenomenon,
      persistent digital ischemia and sometimes develop digital ulcers (DU). Several
      studies have reported an association of carotid artery atherosclerosis with SSc
      by evaluating carotid intima-media thickness (IMT) in SSc patients. However, none
      of those studies analyzed the association between DU and carotid artery
      atherosclerosis in SSc patients. We examined the association of carotid artery
      atherosclerosis with digital ulcers by comparing SSc patients with (n = 48,
      29.5%) and without (n = 206, 70.5%) DU. The demographic and clinical features of
      the SSc patients showed that young age, male sex, anti-topoisomerase I antibody
      positivity, severe skin sclerosis, interstitial lung disease complication and
      cardiac involvements were significantly prevalent in patients with DU. In
      addition, diffuse cutaneous type, anti-RNA polymerase III antibody positivity and
      severe skin sclerosis are more frequent in SSc patients with DU at the extensor
      surface of joints than SSc patients with DU at the digital tip. There were no
      differences in serum lipid level, carotid IMT or plaque score between SSc
      patients with and without DU, suggesting that atherosclerotic changes are not
      primarily involved in the development of DU. 

PMID- 24942497
TI  - To drain or not to drain elective uncomplicated laparoscopic cholecystectomy? A
      systematic review and meta-analysis.
AB  - Laparoscopic cholecystectomy (LC) has largely replaced conventional
      cholecystectomy in the past decade. However, there are still limited data about
      the value of prophylactic sub-hepatic drainage for elective uncomplicated LC. We
      carried out a systematic review of the literature in order to perform a meta
      analysis about this issue. An unrestricted search in MEDLINE, EMBASE and Cochrane
      Library up to 31 December 2013 was performed. Overall, seven high-methodological
      quality randomized controlled trials (RCTs) were included in the meta-analysis,
      resulting in 1310 patients totally. The incidence of abdominal collections, wound
      infection and overall mortality according to the presence or absence of the sub
      hepatic drainage were meta-analyzed. Sub-hepatic drainage showed an increase in
      the abdominal collection rate in patients who underwent elective uncomplicated LC
      (OR 1.56, 95% CI 1.00-2.43) if compared to patients without drainage. A non
      significant correlation was found in overall mortality and infection rates. The
      meta-analysis shows that the presence of the sub-hepatic drainage does not reduce
      the incidence of abdominal collection after uncomplicated LC, whereas it does not
      influence wound infection and mortality rates, postoperative pain and hospital
      stay. 

PMID- 24942498
TI  - The role of the medial frontal cortex in the development of cognitive and social
      affective performance monitoring.
AB  - Adolescence is a time of many cognitive and social-affective changes that are
      important for rapid behavioral adjustment to a variety of environmental demands
      and social contexts. Performance monitoring is one of the most important
      processes for behavioral adjustment; it allows individuals to evaluate outcomes
      of actions and change behavior accordingly. Neuroimaging studies have
      demonstrated that dorsal and ventral subregions of the medial frontal cortex are
      differentially engaged in performance monitoring, depending on the cognitive or
      social-affective dimensions of a task. Based on a review of neuroimaging, ERP,
      and heart rate studies, the implications of these modality-dependent
      contributions are discussed for the development of performance monitoring in
      adolescence.

PMID- 24942499
TI  - Robot-assisted rectal cancer surgery: short-term outcomes for 113 consecutive
      patients.
AB  - PURPOSE: The purpose of this study was to assess the short-term outcome of robot
      assisted laparoscopic surgery (RALS) for rectal cancer, including robotic,
      autonomic nerve-preserving, lateral lymph node dissection (RALLD), a new,
      technically challenging procedure. METHODS: Between December 2011 and August
      2013, 113 consecutive patients underwent RALS for rectal cancer. Surgical
      outcomes, pathological results, and postoperative complications were
      prospectively collected. RESULTS: There were 78 males and 35 females; 30 patients
      (26.5%) had cT1 tumor, 14 (12.4%) had cT2, 56 (49.6%) had cT3, and 12 (10.6%) had
      cT4 tumor. The types of procedures performed were 82 anterior resections, 23
      intersphincteric resections, and 8 abdominoperineal resections. RALLD was
      performed in 38 patients (33.6%). The overall median operative time was 302 (135
      683) min. In cases without RALLD, the median operative time was 242 (135-529)
      min, while median operative time was 486 (320-683) min with RALLD. None of the
      cases was converted to an open or laparoscopic procedure. There was no surgical
      mortality. The overall complication rate for Clavien-Dindo classification grade
      III-IV was 2.7%. Ten patients who developed urinary retention recovered
      completely within 30 days after the operation. CONCLUSIONS: RALS for rectal
      cancer is a technically feasible, less invasive procedure. This procedure can be
      performed with low morbidity and a low conversion rate, even for cases with
      advanced rectal cancer requiring complicated, robot-assisted, lateral lymph node
      dissection.

PMID- 24942500
TI  - Obstructive sleep apnea and optic neuropathy: is there a link?
AB  - Over the last decade, there has been an emerging interest in the link between
      obstructive sleep apnea (OSA) and ocular health. Though the evidence for OSA
      playing a role in cerebrovascular disease risk seems clear, the same cannot be
      said for optic neuropathies. The association between OSA and glaucoma or non
      arteritic anterior ischemic optic neuropathy (NAION) has been postulated to be
      secondary to direct hypoxia or mechanisms of optic nerve head vascular
      dysregulation. Papilledema and increased intracranial pressure have also been
      reported in OSA and are thought to be due to increased cerebral perfusion
      pressure and cerebral venous dilation secondary to hypoxia and hypercapnia. This
      article reviews the evidence for possible pathophysiological links between OSA
      and optic nerve pathology. The epidemiologic and clinical evidence for an
      association, direct or indirect, between OSA and glaucoma, non-arteritic anterior
      ischemic optic neuropathy (NAION), and papilledema or idiopathic intracranial
      hypertension is presented.

PMID- 24942501
TI  - [18F]fluoro-2-deoxyglucose-positron emission tomography for the assessment of
      histopathological response after preoperative chemoradiotherapy in advanced oral
      squamous cell carcinoma.
AB  - BACKGROUND: [(18)F]fluoro-2-deoxyglucose-positron emission tomography (FDG-PET)
      is widely used to evaluate tumor metabolic activity. The aim of this study was to
      evaluate the usefulness of FDG-PET in assessing the histopathological response to
      preoperative concurrent chemoradiotherapy (CRT) in patients with oral squamous
      cell carcinoma (OSCC). METHODS: Forty-five patients with resectable advanced OSCC
      who had received preoperative CRT followed by tumor ablative surgery between
      January 2004 and December 2011 were included in the study. All patients underwent
      FDG-PET before and after preoperative CRT. The maximum standardized uptake value
      (SUVmax) before (pre-SUV) and after preoperative CRT (post-SUV) and the SUVmax
      reduction rate (DeltaSUV %) were used to evaluate the response to preoperative
      CRT. Correlations among SUVmax, histopathological response, and expression of
      cancer antigen Ki-67 and hypoxia-inducible factor-1alpha (HIF-1alpha) were
      analyzed. RESULTS: Preoperative CRT significantly reduced intratumoral FDG uptake
      (P < 0.001). The pre-SUV and post-SUV were significantly lower in patients with a
      pathological complete response (pCR) than in those with a non-pCR (pre-SUV P =
      0.037; post-SUV P = 0.001). DeltaSUV % was higher in patients with pCR than in
      those with non-pCR (P = 0.029). The pre-SUV was significantly correlated with Ki
      67 and HIF-1alpha expression in pretreatment biopsy specimens (Ki-67 P = 0.046, R
      = 0.292; HIF-1alpha P = 0.007, R = 0.385). The expression of both Ki-67 and HIF
      1alpha was significantly lower in patients with pCR than in those with non-pCR
      (Ki-67 P < 0.001; HIF-1alpha P < 0.001). CONCLUSIONS: Low pre-SUV and post-SUV
      and high DeltaSUV % may predict a good histopathological response to preoperative
      CRT. Ki-67 and HIF-1alpha expression in pretreatment biopsy specimens were
      predictors of histopathological response to preoperative CRT.

PMID- 24942503
TI  - Directly drawn poly(3-hexylthiophene) field-effect transistors by
      electrohydrodynamic jet printing: improving performance with surface
      modification.
AB  - In this study, direct micropatterning lines of poly(3-hexylthiophene) (P3HT)
      without any polymer binder were prepared by electrohydrodynamic jet printing to
      form organic field-effect transistors (OFETs). We controlled the dielectric
      surface by introducing self-assembled monolayers and polymer thin films to
      investigate the effect of surface modifications on the characteristics of printed
      P3HT lines and electrical performances of the OFETs. The morphology of the
      printed P3HT lines depended on the surface energy and type of substrate. The
      resulting OFETs exhibited high performance on octadecyltrichlorosilane-modified
      substrates, which was comparable to that of other printed P3HT OFETs. In order to
      realize the commercialization of the OFETs, we also fabricated a large-area
      transistor array, including 100 OFETs and low-operating-voltage flexible OFETs. 

PMID- 24942502
TI  - Long-term persistence and switching patterns among women using osteoporosis
      therapies: 24- and 36-month results from POSSIBLE USTM.
AB  - Persistence with postmenopausal osteoporosis (PMO) medications is not well
      characterized beyond 12 months. Of 3,011 postmenopausal women treated in primary
      care, 36.8 % continued baseline PMO medication during 36 months of follow-up.
      Many factors were associated with nonpersistence, including newly initiating or
      switching therapy, and reporting moderate to severe side effects. INTRODUCTION:
      Persistence with postmenopausal osteoporosis (PMO) medications is not well
      characterized beyond 12 months. We describe 24- and 36-month persistence using
      patient-reported data from women with different PMO treatment histories in the US
      primary care setting. METHODS: Data from 3,011 participants of the Prospective
      Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE USTM,
      10/2005-12/2008) and Kaplan-Meier methods were used to estimate the probability
      of persisting (i.e., not discontinuing or switching PMO agents) with baseline PMO
      medication and hazard ratios for predictors of nonpersistence 24 and 36 months
      after study entry. RESULTS: The probability of persisting with the baseline
      medication was 46.2 % (95 % confidence interval [CI] 44.2-48.1 %) during 24
      months of follow-up and 36.8 % (95 % CI 34.7-38.9 %) during 36 months of follow
      up. In adjusted analyses, newly initiating therapy or switching to a new agent,
      reporting moderate to severe side effects, having lower disease-specific quality
      of life scores, smoking, and residing in the South or West USA (all measured at
      study entry) were independent predictors of nonpersistence in both time periods.
      The majority of participants who discontinued therapy and had the opportunity to
      reinitiate (i.e., discontinued >=4 months before the end of follow-up) restarted
      therapy (24 months 69 %; 36 months 75 %). CONCLUSIONS: In this primary care
      cohort, a minority of women continued their baseline PMO therapy during a 24- to
      36-month follow-up. Supporting patients during the initiation of a new therapy or
      if side effects occur may improve persistence and increase the therapeutic
      benefit of PMO medications.

PMID- 24942504
TI  - Authorship disintegrity in research collaborations: ends do not justify means in
      science.

PMID- 24942505
TI  - Sharing clinical trial data on patient level: opportunities and challenges.
AB  - In recent months one of the most controversially discussed topics among
      regulatory agencies, the pharmaceutical industry, journal editors, and academia
      has been the sharing of patient-level clinical trial data. Several projects have
      been started such as the European Medicines Agency's (EMA) "proactive publication
      of clinical trial data", the BMJ open data campaign, or the AllTrials initiative.
      The executive director of the EMA, Dr. Guido Rasi, has recently announced that
      clinical trial data on patient level will be published from 2014 onwards
      (although it has since been delayed). The EMA draft policy on proactive access to
      clinical trial data was published at the end of June 2013 and open for public
      consultation until the end of September 2013. These initiatives will change the
      landscape of drug development and publication of medical research. They provide
      unprecedented opportunities for research and research synthesis, but pose new
      challenges for regulatory authorities, sponsors, scientific journals, and the
      public. Besides these general aspects, data sharing also entails intricate
      biostatistical questions such as problems of multiplicity. An important issue in
      this respect is the interpretation of multiple statistical analyses, both
      prospective and retrospective. Expertise in biostatistics is needed to assess the
      interpretation of such multiple analyses, for example, in the context of
      regulatory decision-making by optimizing procedural guidance and sophisticated
      analysis methods. 

PMID- 24942507
TI  - Central and peripheral peptides regulating eating behaviour and energy
      homeostasis in anorexia nervosa and bulimia nervosa: a literature review.
AB  - A large body of literature suggests the occurrence of a dysregulation in both
      central and peripheral modulators of appetite in patients with anorexia nervosa
      (AN) and bulimia nervosa (BN), but at the moment, the state or trait-dependent
      nature of those changes is far from being clear. It has been proposed, although
      not definitively proved, that peptide alterations, even when secondary to
      malnutrition and/or to aberrant eating behaviours, might contribute to the
      genesis and the maintenance of some symptomatic aspects of AN and BN, thus
      affecting the course and the prognosis of these disorders. This review focuses on
      the most significant literature studies that explored the physiology of those
      central and peripheral peptides, which have prominent effects on eating
      behaviour, body weight and energy homeostasis in patients with AN and BN. The
      relevance of peptide dysfunctions for the pathophysiology of eating disorders is
      critically discussed.

PMID- 24942508
TI  - Current concepts in the management of prosthetic joint infection.
AB  - Prosthetic joint infection (PJI) is a serious complication of arthroplasty that
      is associated with significant mortality, morbidity and costs. PJI is difficult
      to cure because causative bacteria form and persist in biofilm adherent to the
      prosthesis surface. PJI can be classified into early, delayed or late according
      to the time of onset after insertion of the prosthesis, and this classification
      can help determine pathogenesis and appropriate management. Traditional treatment
      has been with prolonged intravenous antibiotics and prosthesis exchange, which
      has been successful in treating infection but is technically difficult and has
      high rates of associated morbidity. On the basis of in vitro and animal studies,
      interest has turned to the use of antimicrobials that are particularly active
      against biofilm-associated bacteria. Recent clinical evidence shows success in
      more than 77% of early PJI with surgical debridement, retention of prosthesis and
      the use of rifampicin-based combinations for staphylococcal PJI. Fluoroquinolones
      are preferred for Gram-negative PJI. Optimal antimicrobial treatment duration and
      the management of polymicrobial, enterococcal, fungal and culture-negative
      infections are still yet to be defined but will become more clear as the results
      of current research comes to hand. 

PMID- 24942506
TI  - Modified bortezomib, adriamycin and dexamethasone (PAD) regimen in advanced
      multiple myeloma.
AB  - The PAD regime, composed of bortezomib, adriamycin and dexamethasone, improves
      the outcomes of patients with advanced multiple myeloma (MM), but at the same
      time produces high frequency of serious toxic side effects. For the first time,
      we evaluated the efficacy and safety of a bortezomib-dose-reduced PAD regime in
      the treatment of relapsed/refractory MM in this clinical study. Forty-five
      patients were treated with two to six 21-day cycles of PAD, comprising bortezomib
      at 1.3 mg/m(2) (P1AD, n = 21) or 1.0 mg/m(2) (P2AD, n = 24) (days 1, 4, 8, 11),
      adriamycin at 9 mg/m(2) (days 1-4) and dexamethasone at 40 mg/day (days 1-4).
      Overall, 36 patients (80 %) showed at least partial remission (PR), in which 9
      cases (20 %) showed complete remission (CR) and 10 cases (22 %) showed very good
      partial remission (VGPR). The efficacy of PAD regimen in advanced MM patients was
      not related to the traditional prognostic factors. There was no significant
      difference between P1AD and P2AD in the rates of PR, CR or VGPR, 1.5-year
      progression-free survival (PFS), and overall survival (OS) (81 % vs. 79 %, 48 %
      vs. 38 %, 64 % vs. 59 %, and 85 % vs. 73 %, respectively). However, the grade 3-4
      toxic effects, including thrombocytopenia (13 % vs. 38 %), peripheral neuropathy
      (8 % vs. 33 %) and 3-4 grade gastrointestinal reaction (13 % vs. 43 %), were
      markedly inhibited after P2AD compared to P1AD (P < 0.05). The bortezomib-dose
      reduced PAD regime reduced the incidence of adverse reactions without affecting
      the treatment efficacy in patients with advanced MM.

PMID- 24942510
TI  - Comparison of Hospital Consumer Assessment of Healthcare Providers and Systems
      patient satisfaction scores for specialty hospitals and general medical
      hospitals: confounding effect of survey response rate.
AB  - BACKGROUND: Specialty hospitals are a subset of acute-care hospitals that provide
      a narrower set of services than general medical hospitals (GMHs), predominantly
      in areas such as cardiac disease and surgery. Although specialty hospitals also
      advertise high patient satisfaction, this has not been examined using national
      data. We examined the differences in Hospital Consumer Assessment of Healthcare
      Providers and Systems (HCAHPS) satisfaction scores in a national sample. METHODS:
      HCAHPS results were obtained for July 2007 to June 2010. Specialty hospitals were
      identified using the American Hospital Association's Annual Survey, the Physician
      Hospital Association's directory, a name search of hospitals on the HCAHPS
      database, contact with experts, and online searches. Multiple linear regression
      was performed to examine the relationship between overall satisfaction and
      hospital specialty status, survey response rate, and subdomains of patient
      satisfaction. RESULTS: We identified 188 specialty hospitals and 4368 GMHs.
      Specialty hospitals were disproportionately located in states that do not require
      Certification Of Need (47.9%), and had a higher overall patient satisfaction
      score (86.6 vs 67.8%, P < 0.0001) and survey response rates (49.6% vs 32.2%, P <
      0.0001). After adjusting for response rate, the difference in overall patient
      satisfaction decreased by >50% (from 18.5 to 8.7) but remained significantly
      higher (P < 0.0001). Similar results were obtained for patient satisfaction
      subdomains. CONCLUSION: Specialty hospitals have a significantly higher overall
      HCAHPS patient satisfaction score than GMHs, although more than half of this
      difference disappears when adjusted for survey response rate. Comparisons among
      healthcare organizations should take into account survey response rates.

PMID- 24942509
TI  - Intercellular adhesion molecule-1 K469E and angiotensinogen T207M polymorphisms
      in coronary slow flow.
AB  - OBJECTIVE: To investigate intercellular adhesion molecule-1 (ICAM1) and
      angiotensinogen (AGT) gene polymorphisms, as related to atherosclerosis and
      endothelial dysfunction, in coronary slow flow (CSF). SUBJECTS AND METHODS: The
      participants in this study were 48 patients with CSF and 67 patients with normal
      coronary flow as controls. The K469E polymorphism of ICAM1 (rs5498) and the T207M
      polymorphism of AGT (rs4762) were determined using the polymerase chain reaction
      amplification method. RESULTS: Baseline demographic parameters were similar in
      both groups. The mean thrombolysis in myocardial infarction frame count was
      significantly higher in patients with CSF (23.8 +/- 5.1) compared to the controls
      (13.3 +/- 2.6, p < 0.001). A significant association was found between the ICAM1
      K allele and CSF (OR: 1.96, 95% CI: 1.15-3.35, p = 0.013). There was no
      difference in the frequency of AGT T207M genotypes in the patients with CSF and
      the control subjects. CONCLUSION: This study showed that K469E polymorphisms of
      ICAM1 that play a role in atherosclerotic pathogenesis are related to CSF.

PMID- 24942511
TI  - Circulating immature granulocytes with T-cell killing functions predict sepsis
      deterioration*.
AB  - OBJECTIVES: Primary objective was to identify leukocyte subsets that could
      predict the early evolution of sepsis at 48 hours (i.e., deterioration or
      stability/improvement). Secondary objectives were to evaluate the prognostic
      value of leukocyte subsets on mortality and immunosuppressive properties of
      immature granulocytes. DESIGN: Twenty-three peripheral blood leukocyte subsets
      were analyzed using a new-generation 10-color flow cytometry. T-cell killing
      activity of immature granulocytes was explored using a sorting method
      specifically developed. SETTING: ICUs and emergency departments. PATIENTS: All
      patients admitted to emergency department and ICU for sepsis ongoing for less
      than 24 hours were eligible. Exclusion criteria were pregnancy, age less than 18
      years, solid tumors, HIV infection, hematological or inflammatory conditions, and
      immunosuppressive drugs. Finally, 177 patients were included. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: The two most salient features of sepsis were
      decreased CD10 (CD10) and CD16 (CD16) expressions on granulocytes. With a
      threshold of 90% of CD10 and 15% of CD16 granulocytes, these immunophenotypic
      features, which are those of immature granulocytes, predicted sepsis
      deterioration at 48 hours with a sensitivity of 57% and 70% and a specificity of
      78% and 82%, respectively. Survival rate at day 30 was 99% for patients without
      CD10 and CD16, 85% for patients with increased CD16 only, and 63% for patients
      with increased CD16 and CD10 granulocytes (p < 0.001). Among CD16 immature
      granulocytes, we identified a CD14/CD24 myeloid-derived suppressor cell subset
      with the capability of killing activated T cells. Consistently, an excess of CD16
      immature granulocytes was associated with both CD3 and CD4 T-cell lymphopenia in
      deteriorating patients. CONCLUSIONS: Circulating immature granulocytes predicted
      early sepsis deterioration and were enriched in myeloid-derived suppressor cells
      which could be responsible for immunosuppression through the induction of T-cell
      lymphopenia.

PMID- 24942513
TI  - Habitat specificity of a threatened and endemic, cliff-dwelling halophyte.
AB  - Coastal areas and other saline environments are major contributors to regional
      and global biodiversity patterns. In these environments, rapidly changing
      gradients require highly specialized plants like halophytes. In European coastal
      cliff-tops, rocky and sandy seashores, and saltmarshes, typical halophytes from
      the genus Limonium are commonly found. Among them, the aneuploid tetraploid (2n =
      4x = 35, 36, 37) Limonium multiflorum, endemic to the west coast of Portugal, is
      an interesting case study for investigating the ecology and conservation of a
      halophyte agamospermic species. Although it is listed in the IUCN red list of
      threatened species, information on its population size or rarity, as well as its
      ecology, in some respects is still unknown. Field surveys in the largest known
      population were performed (Raso cape, Portugal) in order to determine habitat
      requirements and conservation status. A total of 88 quadrats were monitored, 43
      of which contained at least one L. multiflorum individual. For each sampled
      quadrat, four abiotic and four biotic variables as well as two spatially derived
      variables were recorded. Principal component analysis and cluster analysis showed
      narrow habitat specificity for this species which appeared to be intolerant to
      competition with invasive alien plants. We conclude that in situ conservation in
      a local 'hotspot' of this rare and vulnerable species emerges as a priority in
      order to ensure that biodiversity is not lost. 

PMID- 24942514
TI  - Effects of omeprazole on sleep disturbance: randomized multicenter double-blind
      placebo-controlled trial.
AB  - OBJECTIVES: Gastroesophageal reflux is considered to cause sleep disturbance,
      whereas proton pump inhibitor (PPI) administration is reported to improve
      insomnia associated with gastroesophageal reflux disease (GERD). The majority of
      patients with gastroesophageal reflux are asymptomatic and a significant number
      with erosive esophagitis are also reported to be asymptomatic. We examined
      whether PPI administration has a therapeutic effect for improving insomnia in
      patients without reflux symptoms in the same manner as patients with reflux
      symptoms. METHODS: We performed a randomized multicenter double-blind placebo
      controlled trial using 176 patients with insomnia regardless of the presence of
      reflux symptoms. The patients were divided into those administered omeprazole (20
      mg) or a placebo for 14 days. Four self-reporting questionnaires, QOLRAD-J
      (Japanese translation of Quality of Life in Reflux and Dyspepsia), Pittsburg
      Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and a sleep diary,
      were used for evaluating GERD-related quality of life (QOL) and sleep
      disturbance. RESULTS: We evaluated 171 patients with insomnia, of whom 69 had
      typical reflux symptoms. Omeprazole statistically significantly improved GERD
      related QOL from 30.8+/-0.7 to 33.0+/-0.5 (P<0.01) (QOLRAD-J, total) and from
      6.0+/-0.2 to 6.6+/-0.1 (P<0.01) (QOLRAD-J, sleep-related) when administrated to
      patients with reflux symptoms. Omeprazole also improved insomnia significantly
      better than the placebo in patients with reflux symptoms; PSQI, from 9.3+/-0.5 to
      7.9+/-0.5 (P<0.01) and sleep diary, from 2.1+/-0.1 to 1.8+/-0.1 (P<0.01). On the
      other hand, the therapeutic effects of omeprazole and the placebo were not
      different in patients without reflux symptoms. CONCLUSIONS: Our results showed
      that PPI administration is effective only for insomnia in patients with reflux
      symptoms.

PMID- 24942516
TI  - American Diabetes Association issues new guidelines for type 1 diabetes.

PMID- 24942517
TI  - [Formula: see text]evidence of neuropsychological dysfunction in Stevens-Johnson
      Syndrome and toxic epidermal necrolysis: case report.
AB  - Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) is a
      potentially life-threatening critical illness affecting multiple organ systems
      including the peripheral and central nervous system. This case report involves a
      young man who was diagnosed with SJS/TEN at age 16 and underwent
      neuropsychological assessment at age 21. Results indicate a diffuse pattern of
      cerebral compromise and represent a decline from premorbid level of functioning.
      The etiology of the cognitive impairment in this patient is likely multifactorial
      with possible pathophysiologic mechanisms including hypoxemia, metabolic acid
      base perturbations, hyperglycemia, and delirium, as well as sepsis and
      inflammation. 

PMID- 24942515
TI  - Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient
      male patients and female symptomatic carriers.
AB  - BACKGROUND: Crohn disease is an inflammatory bowel disease (IBD) with a complex
      mode of inheritance. Although nucleotide binding and oligomerization domain
      containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease
      remains unknown in the majority of the cases. X-linked inhibitor of apoptosis
      (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has
      been reported in some XIAP-deficient patients. OBJECTIVE: We characterize the IBD
      affecting a large cohort of patients with mutations in XIAP and examine the
      possible pathophysiologic mechanisms. METHODS: We performed a phenotypical and
      histologic analysis of the IBD affecting 17 patients with hemizygous mutations in
      XIAP, including 3 patients identified by screening 83 patients with pediatric
      onset IBD. The X chromosome inactivation was analyzed in female carriers of
      heterozygous XIAP mutations, including 2 adults with IBD. The functional
      consequences of XIAP deficiency were analyzed. RESULTS: Clinical presentation and
      histology of IBD in patients with XIAP deficiency overlapped with those of
      patients with Crohn disease. The age at onset was variable (from 3 months to 41
      years), and IBD was severe and difficult to treat. In 2 patients hematopoietic
      stem cell transplantation fully restored intestinal homeostasis. Monocytes of
      patients had impaired NOD2-mediated IL-8 and monocyte chemoattractant protein 1
      (MCP-1) production, as well as IL-10, in response to NOD2 and Toll-like receptor
      2/4 costimulation. Nucleotide binding and oligomerization domain containing 1
      (NOD1)-mediated IL-6 and IL-8 production was defective in fibroblasts from XIAP
      deficient patients. The 2 heterozygous female carriers of XIAP mutations with IBD
      displayed abnormal expression of the XIAP mutated allele, resulting in impaired
      activation of the NOD2 pathway. CONCLUSION: IBD in patients with XIAP deficiency
      is similar to Crohn disease and is associated with defective NOD2 function in
      monocytes. Importantly, we report that it is not restricted to male patients
      because we identified 2 symptomatic female heterozygous carriers of XIAP
      mutations.

PMID- 24942518
TI  - Comparison of diffusive gradients in thin film technique with traditional methods
      for evaluation of zinc bioavailability in soils.
AB  - The technique of diffusive gradients in thin film (DGT) has been shown to be a
      promising tool to assess zinc (Zn) bioavailability in soils, but there exists
      considerable debate on its suitability. In this study, Zn bioavailability was
      systematically investigated in wheat- and maize-grown soils using this technique
      and seven traditional methods, including soil solution concentration and six
      widely used single-step extraction methods (HAc, EDTA, NaAc, NH4Ac, CaCl2, and
      MgCl2). The concentrations of Zn in the shoots and roots of these two plant
      species increased continuously with increasing additions of Zn to the soils,
      accompanied by significant decreases in shoot biomass and root biomass at Zn
      concentrations greater than 400 mg kg(-1) for maize and 800 mg kg(-1) for wheat.
      Zinc uptake and accumulation was higher in maize roots than in wheat roots. Both
      the concentrations of bioavailable Zn measured by DGT (CDGT) and soil solutions
      (Csol) increased linearly with increasing additions of Zn to the soils, while no
      strong linear relationships were observed for the extraction methods. Higher
      concentrations of extractable Zn, lower values of Csol, and larger values of R
      (i.e., the ratio of CDGT to Csol) were observed in maize-grown soils compared
      with those of wheat-grown soils, while the values of C DGT between the two plants
      were similar. These findings demonstrate that there likely exists a stronger
      resupply of Zn from the soil solid phases in maize-grown soils to satisfy a
      higher Zn uptake and accumulation in this plant. Linear correlation analyses
      showed that CDGT had the highest correlation coefficients with plant Zn
      concentrations compared with other traditional methods, implying that the DGT
      technique is more sensitive and robust in reflecting Zn bioavailability in soils
      to plants.

PMID- 24942520
TI  - Second-line chemotherapy in recurrent clear cell ovarian cancer: results from the
      multicenter italian trials in ovarian cancer (MITO-9).
AB  - BACKGROUND AND AIMS: Ovarian clear cell carcinoma (CCC) has a poorer prognosis
      than other subtypes of ovarian cancer. In this study, we evaluated the
      responsiveness to second-line chemotherapy in recurrent ovarian CCC. METHODS: The
      MITO-9 project investigated a cohort of patients observed between 1991 and 2007
      in 20 centers. We identified 72 out of 240 patients with recurrent disease (28%
      stage I-II and 72% stage III-IV at diagnosis). RESULTS: In 56% of patients, the
      clear cell histology was pure. Twenty-five patients were platinum-resistant, 18
      were platinum-sensitive with a platinum-free interval (PFI) of 6-12 months, and
      29 had a PFI >12 months. Upon recurrence, 47% of patients were treated with
      platinum chemotherapy according to the PFI. The overall response rate (RR) to
      platinum was 80%, with 55, 100, and 80% RR in patients with PFI of 6-12, >12, and
      >24 months. The RR to nonplatinum agents in resistant patients was 33%. Among the
      nonplatinum agents used in primary and secondary resistant cases, gemcitabine,
      administered in 12 cases, had a higher activity (RR = 66%) compared to topotecan
      or liposomal doxorubicin (n = 31; RR = 33 and 10%, respectively). CONCLUSIONS:
      This study showed that the treatment of recurrent ovarian CCC should be based on
      the PFI as in the other subtypes. Data in platinum-resistant patients suggest
      gemcitabine as the drug with the highest activity. We recommend that gemcitabine
      be studied prospectively in a phase 2 trial.

PMID- 24942519
TI  - Assessment of both environmental cytotoxicity and trace metal pollution using
      Populus simonii Carr. as a bioindicator.
AB  - The level of environmental pollution in the city of Ivano-Frankivsk (Western
      Ukraine) has been assessed by means of roadside poplar trees as bioindicators.
      Dividable apical meristem cells of rudimentary leaves were quantitatively
      analysed for mitotic activity and distribution. Anaphases were further examined
      for chromosomal aberrations. Male catkins were also examined for sterile pollens.
      Accumulation of trace elements in vegetative buds was also evaluated in order to
      reveal source(s) of environmental pollution. Poplar trees growing in the urban
      environment proved to have increased chromosomal aberrations (up to 4-fold) and
      increased pollen sterility (up to 4-fold) as well as decreased mitotic activity
      (by factor 1.5) as compared to control sampling site. The biomarker data
      correlate moderately with increased (up to 4-fold) concentrations of Ni, Zn, Pb,
      Cd and Cu in vegetative tissues suggesting that probable cause of the
      environmental cytotoxicity may be vehicle emissions. The maximum increase in
      chromosomal aberrations (7-fold) and the minimum mitotic activity (half of the
      control one) were recorded in poplar trees growing in industrial suburb in
      vicinity of large cement production plant. Taking in mind insignificant
      bioaccumulation of trace elements in the industrial suburb, the high
      environmental toxicity has been ascribed to contamination in cement and asbestos
      particulates. 

PMID- 24942521
TI  - The possible involvement of genetic variants of NET1 in the etiology of attention
      deficit/hyperactivity disorder comorbid with oppositional defiant disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and oppositional
      defiant disorder (ODD) often coexist and shared some genetic influences. Evidence
      from the existing literature indicated that comorbid with ODD may increase the
      heterogeneity of ADHD genetics. Our present study sought to investigate the role
      of norepinephrine transporter gene (NET1) for ADHD comorbid with ODD. METHODS:
      Six single nucleotide polymorphisms (SNPs) of NET1 were genotyped for a total of
      1,815 ADHD cases, including 587 subjects (32.3%) with ODD. Chi-square tests were
      conducted for pseudo case-control study comparing allelic and genotypic
      distributions between ADHD with and without ODD. Among them, there were 1,249
      probands together with their parents composing trios for family-based association
      studies using transmission disequilibrium tests (TDTs). In addition, 1,337 ADHD
      probands have detailed information of ODD symptoms and were included for
      quantitative analyses with genotypes using analyses of covariance (ANCOVA). To
      consider the overlap and correlation of other comorbidities with ODD and
      eliminate their potential confounding effect, we further repeated above analyses
      for 'pure ADHD+ODD' versus 'ADHD-only' after excluding other comorbidities except
      for ODD. RESULTS: The pseudo case-control study showed different allelic and
      genotypic distributions of SNP rs3785143 between ADHD with ODD and those without
      ODD. Family-based association tests indicated overtransmission of the T allele of
      rs3785143 in ADHD with ODD trios, but no biased transmission in those without
      ODD. ANCOVA showed association between genotypes of rs3785143 with ODD symptoms
      in ADHD probands, especially with 'Argumentative/Defiant Behavior (ADB)'
      dimension after controlling gender, age, clinical subtypes and intelligence.
      Above association still existed after removing the samples with other
      comorbidities. CONCLUSION: NET1 was associated with comorbidity of ODD and ODD
      symptoms in ADHD probands. Our findings emphasize the importance of considering
      the comorbidity of ODD in ADHD genetic studies, especially ADHD with ADB.
      However, further replication in independent sample or different populations is
      still needed.

PMID- 24942512
TI  - Prevalence and impact of active and passive cigarette smoking in acute
      respiratory distress syndrome.
AB  - OBJECTIVES: Cigarette smoke exposure has recently been found to be associated
      with increased susceptibility to trauma- and transfusion-associated acute
      respiratory distress syndrome. We sought to determine 1) the incidence of
      cigarette smoke exposure in a diverse multicenter sample of acute respiratory
      distress syndrome patients and 2) whether cigarette smoke exposure is associated
      with severity of lung injury and mortality in acute respiratory distress
      syndrome. DESIGN: Analysis of the Albuterol for the Treatment of Acute Lung
      Injury and Omega Acute Respiratory Distress Syndrome Network studies. SETTING:
      Acute Respiratory Distress Syndrome Network hospitals. PATIENTS: Three hundred
      eighty-one patients with acute respiratory distress syndrome. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: 4-(Methylnitrosamino)-1-(3-pyridyl)-1
      butanol, a validated tobacco-specific marker, was measured in urine samples from
      subjects enrolled in two National Heart, Lung, and Blood Institute Acute
      Respiratory Distress Syndrome Network randomized controlled trials. Urine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol levels were consistent with active
      smoking in 36% of acute respiratory distress syndrome patients and with passive
      smoking in 41% of nonsmokers (vs 20% and 40% in general population,
      respectively). Patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels
      in the active smoking range were younger and had a higher incidence of alcohol
      misuse, fewer comorbidities, lower severity of illness, and less septic shock at
      enrollment compared with patients with undetectable 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol levels. Despite this lower severity of illness, the severity
      of lung injury did not significantly differ based on biomarker-determined smoking
      status. Cigarette smoke exposure was not significantly associated with death
      after adjusting for differences in age, alcohol use, comorbidities, and severity
      of illness. CONCLUSIONS: In this first multicenter study of biomarker-determined
      cigarette smoke exposure in acute respiratory distress syndrome patients, we
      found that active cigarette smoke exposure was significantly more prevalent among
      acute respiratory distress syndrome patients compared to population averages.
      Despite their younger age, better overall health, and lower severity of illness,
      smokers by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol had similar severity of
      lung injury as patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol. These findings suggest that active cigarette smoking may increase
      susceptibility to acute respiratory distress syndrome in younger, healthier
      patients.

PMID- 24942523
TI  - When will there be a cure for dementia?

PMID- 24942522
TI  - Luminescent threat: toxicity of light stick attractors used in pelagic fishery.
AB  - Light sticks (LS) are sources of chemiluminescence commonly used in pelagic
      fishery, where hundreds are discarded and reach the shores. Residents from
      fishing villages report an improper use of LS contents on the skin. Given the
      scarce information regarding LS toxicity, the effects of LS solutions in cell
      cultures were evaluated herein. Loss of viability, cell cycle changes and DNA
      fragmentation were observed in HepG2 cell line and skin fibroblasts. A non
      cytotoxic LS concentration increased the occurrence of the mutagenic lesion
      1,N(6)-epsilondAdo in HepG2 DNA by three-fold. Additionally, in vitro incubations
      of spent LS contents with DNA generated dGuo-LS adducts, whose structure
      elucidation revealed the presence of a reactive chlorinated product. In
      conclusion, the LS contents were found to be highly cyto- and genotoxic. Our data
      indicate an urgent need for LS waste management guidelines and for adequate
      information regarding toxic outcomes that may arise from human exposure. 

PMID- 24942525
TI  - Examining functional and social determinants of depression in community-dwelling
      older adults: implications for practice.
AB  - Coping with declining health, physical illnesses and complex medical regimens,
      which are all too common among many older adults, requires significant lifestyle
      changes and causes increasing self-management demands. Depression occurs in
      community-dwelling older adults as both demands and losses increase, but this
      problem is drastically underestimated and under-recognized. Depressive symptoms
      are often attributed to physical illnesses and thus overlooked, resulting in lack
      of appropriate treatment and diminished quality of life. The purpose of this
      study is to assess prevalence of depressive symptoms in community-dwelling older
      adults with high levels of co-morbidity and to identify correlates of depression.
      In this sample of 533 homebound older adults screened (76.1% female, 71.8% white,
      mean age 78.5 years) who were screened using the Geriatric Depression Scale (SF),
      35.9% scored greater than 5. Decreased satisfaction with family support (p <<
      0.001) and functional status (p <= 0.001) and increased loneliness (p < 0.001)
      were significant independent predictors of depression status in this sample;
      thus, these factors should be considered when planning care.

PMID- 24942524
TI  - Exemplars of complex assessment and care for hospitalized older adults: genital
      herpes infection.

PMID- 24942528
TI  - NICHE Solutions - Ninth in a series: focus on patient function.

PMID- 24942529
TI  - Relatedness defies biogeography: the tale of two island endemics (Acacia
      heterophylla and A. koa).
AB  - Despite the normally strong link between geographic proximity and relatedness of
      recently diverged taxa, truly puzzling biogeographic anomalies to this
      expectation exist in nature. Using a dated phylogeny, population genetic
      structure and estimates of ecological niche overlap, we tested the hypothesis
      that two geographically very disjunct, but morphologically very similar, island
      endemics (Acacia heterophylla from Reunion Island and A. koa from the Hawaiian
      archipelago) are the result of dispersal between these two island groups, rather
      than independent colonization events from Australia followed by convergent
      evolution. Our genetic results indicated that A. heterophylla renders A. koa
      paraphyletic and that the former colonized the Mascarene archipelago directly
      from the Hawaiian Islands <= 1.4 million yr ago. This colonization sequence was
      corroborated by similar ecological niches between the two island taxa, but not
      between A. melanoxylon from Australia (a sister, and presumed ancestral, taxon to
      A. koa and A. heterophylla) and Hawaiian A. koa. It is widely accepted that the
      long-distance dispersal of plants occurs more frequently than previously thought.
      Here, however, we document one of the most exceptional examples of such
      dispersal. Despite c. 18 000 km separating A. heterophylla and A. koa, these two
      island endemics from two different oceans probably represent a single taxon as a
      result of recent extreme long-distance dispersal. 

PMID- 24942530
TI  - Dietary self-efficacy predicts AHEI diet quality in women with previous
      gestational diabetes.
AB  - PURPOSE: The purpose of this study was to examine the association of
      intrapersonal influences of diet quality as defined by the Health Belief Model
      constructs in women with recent histories of gestational diabetes. METHODS: A
      descriptive, correlational, cross-sectional design was used to analyze
      relationships between diet quality and intrapersonal variables, including
      perceptions of threat of type 2 diabetes mellitus development, benefits and
      barriers of healthy eating, and dietary self-efficacy, in a convenience sample of
      75 community-dwelling women (55% minority; mean age, 35.5 years; SD, 5.5 years)
      with previous gestational diabetes mellitus. Diet quality was defined by the
      Alternative Healthy Eating Index (AHEI). Multiple regression was used to identify
      predictors of AHEI diet quality. RESULTS: Women had moderate AHEI diet quality
      (mean score, 47.6; SD, 14.3). Only higher levels of education and self-efficacy
      significantly predicted better AHEI diet quality, controlling for other
      contributing variables. CONCLUSIONS: There is a significant opportunity to
      improve diet quality in women with previous gestational diabetes mellitus.
      Improving self-efficacy may be an important component to include in nutrition
      interventions. In addition to identifying other important individual components,
      future studies of diet quality in women with previous gestational diabetes
      mellitus are needed to investigate the scope of influence beyond the individual
      to potential family, social, and environmental factors.

PMID- 24942532
TI  - Social media for public health: an exploratory policy analysis.
AB  - BACKGROUND: To accomplish the aims of public health practice and policy today,
      new forms of communication and education are being applied. Social media are
      increasingly relevant for public health and used by various actors. Apart from
      benefits, there can also be risks in using social media, but policies regulating
      engagement in social media is not well researched. This study examined European
      public health-related organizations' social media policies and describes the main
      components of existing policies. METHODS: This research used a mixed methods
      approach. A content analysis of social media policies from European institutions,
      non-government organizations (NGOs) and social media platforms was conducted.
      Next, individuals responsible for social media in their organization or projects
      completed a survey about their social media policy. RESULTS: Seventy-five per
      cent of institutions, NGOs and platforms had a social media policy available. The
      primary aspects covered within existing policies included data and privacy
      protection, intellectual property and copyright protection and regulations for
      the engagement in social media. Policies were intended to regulate staff use, to
      secure the liability of the institution and social responsibility. Respondents
      also stressed the importance of self-responsibility when using social media.
      CONCLUSIONS: This study of social media policies for public health in Europe
      provides a first snapshot of the existence and characteristics of social media
      policies among European health organizations. Policies tended to focus on legal
      aspects, rather than the health of the social media user. The effect of such
      policies on social media adoption and usage behaviour remains to be examined.

PMID- 24942534
TI  - Opioid use in Albuquerque, New Mexico: a needs assessment of recent changes and
      treatment availability.
AB  - BACKGROUND: New Mexico has consistently high rates of drug-induced deaths, and
      opioid-related treatment admissions have been increasing over the last two
      decades. Youth in New Mexico are at particular risk: they report higher rates of
      nonmedical prescription opioid use than those over age 25, are more likely than
      their national counterparts to have tried heroin, and represent an increasing
      proportion of heroin overdoses. METHODS: Commissioned by the City of Albuquerque,
      semistructured interviews were conducted from April to June of 2011 with 24
      substance use treatment agencies and eight key stakeholders in Albuquerque to
      identify recent changes in the treatment-seeking population and gaps in treatment
      availability. Themes were derived using template analysis and data were analyzed
      using NVivo 9 software. RESULTS: Respondents reported a noticeable increase in
      youth seeking treatment for opioid use and a general increase in nonmedical
      prescription opioid use. Most noted difficulties with finding buprenorphine
      providers and a lack of youth services. Additionally, stigma, limited interagency
      communication and referral, barriers to prescribing buprenorphine, and a lack of
      funding were noted as preventing opioid users from quickly accessing effective
      treatment. CONCLUSIONS: Recommendations for addressing these issues include
      developing youth-specific treatment programs, raising awareness about opioid use
      among youth, increasing the availability of buprenorphine through provider
      incentives and education, developing a resource guide for individuals seeking
      treatment in Albuquerque, and prioritizing interagency communication and
      referrals.

PMID- 24942531
TI  - Predictors of physical inactivity in men and women with type 2 diabetes from the
      Detection of Ischemia in Asymptomatic Diabetics (DIAD) study.
AB  - PURPOSE: The purpose of this secondary analysis was to determine changes in
      physical inactivity from baseline to 5 years and to identify factors associated
      with and predictive of physical inactivity among individuals with type 2 diabetes
      enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study.
      METHODS: DIAD was a prospective randomized screening trial that assessed the
      prevalence of silent ischemia in asymptomatic patients with type 2 diabetes.
      Subjects were recruited from diabetes and primary care practices at 14 centers
      throughout the United States and Canada. This is a secondary data analysis of the
      physical activity data (type and hours/week) collected. No intervention was
      conducted. RESULTS: In all subjects, physical inactivity rose from 24% at
      baseline to 33% at 5 years (S = 28.93; P < .0001). This change was significant in
      both men (S = 11.44; P < .0001), increasing from 23% to 31%, and women (S =
      18.05; P < .0001), increasing from 25% to 36%. Gender differences were noted in
      several factors associated with baseline physical inactivity as well as in
      factors predictive of physical inactivity at 5 years. Important factors
      associated at both time points included lower level of education, current
      employment, presence of peripheral and autonomic neuropathy, and indicators of
      overweight/obesity. Baseline physical inactivity was strongly predictive of
      physical inactivity at 5 years (odds ratio, 3.27; 95% confidence interval, 2.36
      4.54; P < .0001). CONCLUSIONS: Gender-related differences were noted in factors
      associated with and predictive of physical inactivity.

PMID- 24942533
TI  - Biosynthesis of fluorescent gold nanoparticles using an edible freshwater red
      alga, Lemanea fluviatilis (L.) C.Ag. and antioxidant activity of biomatrix loaded
      nanoparticles.
AB  - Biosynthesis of gold nanoparticles has been accomplished via reduction of an
      aqueous chloroauric acid solution with the dried biomass of an edible freshwater
      epilithic red alga, Lemanea fluviatilis (L.) C.Ag., as both reductant and
      stabilizer. The synthesized nanoparticles were characterized by UV-visible,
      powder X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier
      transform infrared (FT-IR), and dynamic light scattering (DLS) studies. The UV
      visible spectrum of the synthesized gold nanoparticles showed the surface plasmon
      resonance (SPR) at around 530 nm. The powder XRD pattern furnished evidence for
      the formation of face-centered cubic structure of gold having average crystallite
      size 5.9 nm. The TEM images showed the nanoparticles to be polydispersed, nearly
      spherical in shape and have sizes in the range 5-15 nm. The photoluminescence
      spectrum of the gold nanoparticles excited at 300 nm showed blue emission at
      around 440 nm. Gold nanoparticles loaded within the biomatrix studied using a
      modified 2,2-diphenyl-1-picrylhydrazyl (DPPH) method exhibited pronounced
      antioxidant activity. 

PMID- 24942535
TI  - Using an aqueous two-phase polymer-salt system to rapidly concentrate viruses for
      improving the detection limit of the lateral-flow immunoassay.
AB  - The development of point-of-need (PON) diagnostics for viruses has the potential
      to prevent pandemics and protects against biological warfare threats. Here we
      discuss the approach of using aqueous two-phase systems (ATPSs) to concentrate
      biomolecules prior to the lateral-flow immunoassay (LFA) for improved viral
      detection. In this paper, we developed a rapid PON detection assay as an
      extension to our previous proof-of-concept studies which used a micellar ATPS. We
      present our investigation of a more rapid polymer-salt ATPS that can drastically
      improve the assay time, and show that the phase containing the concentrated
      biomolecule can be extracted prior to macroscopic phase separation equilibrium
      without affecting the measured biomolecule concentration in that phase. We could
      therefore significantly decrease the time of the diagnostic assay with an early
      extraction time of just 30 min. Using this rapid ATPS, the model virus
      bacteriophage M13 was concentrated between approximately 2 and 10-fold by
      altering the volume ratio between the two phases. As the extracted virus-rich
      phase contained a high salt concentration which destabilized the colloidal gold
      indicator used in LFA, we decorated the gold nanoprobes with polyethylene glycol
      (PEG) to provide steric stabilization, and used these nanoprobes to demonstrate a
      10-fold improvement in the LFA detection limit. Lastly, a MATLAB script was used
      to quantify the LFA results with and without the pre-concentration step. This
      approach of combining a rapid ATPS with LFA has great potential for PON
      applications, especially as greater concentration-fold improvements can be
      achieved by further varying the volume ratio. Biotechnol. Bioeng. 2014;111: 2499
      2507. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24942537
TI  - Real-time 4D phase unwrapping applied to magnetic resonance elastography.
AB  - PURPOSE: Phase amplitude is a source of signal in magnetic resonance elastography
      (MRE) experiments but its exploitation in experimental design has been limited
      due to the challenges of phase wrap. This study addressed this aspect of MRE
      through new developments in algorithms, heuristic strategy, and user interface.
      METHODS: A test dataset with systematic variation of three parameters-nested
      wrap, gradient, and noise level-was developed to choose phase-unwrapping
      algorithms and to analyze their performance. A new application, PhaseTools, was
      developed that implemented three phase-unwrapping algorithms that adhere to a
      "real-time" criterion of less than 3 min for a four-dimensional MRE acquisition.
      Two of the algorithms extend previously published algorithms and one was newly
      developed. The algorithms were then applied to five datasets from MRE, two
      typical cases and three edge cases that were particularly challenging in one of
      the three parameters. RESULTS: The performance of the PhaseTools algorithms on
      the test dataset was comparable to two widely cited algorithms that take hours or
      days to complete. Guidelines for the optimal use of each algorithm are
      established. CONCLUSION: PhaseTools enables the substantial increase of signal-to
      noise in MRE experiments at negligible additional computational cost. PhaseTools
      is freely released with this study, making robust real-time phase unwrapping
      available to any group using phase-based imaging.

PMID- 24942536
TI  - Polymeric Plerixafor: effect of PEGylation on CXCR4 antagonism, cancer cell
      invasion, and DNA transfection.
AB  - PURPOSE: To determine the effect of PEG modification on pharmacologic and gene
      delivery properties of polymeric CXCR4 antagonist based on Plerixafor. METHODS:
      Polymeric Plerixafor (PAMD) was synthesized from Plerixafor (AMD3100) and grafted
      with different amounts of PEG (2 kDa). CXCR4 antagonism of the synthesized
      polymers was determined using receptor redistribution assay. Inhibition of cancer
      cell invasion by the polyplexes of the synthesized polymers was assessed using
      Boyden-chamber method. Transfection activity of DNA polyplexes formed with the
      synthesized polymers was evaluated in U2OS osteosarcoma and B16F10 melanoma
      cells. RESULTS: Our results demonstrate that modification of PAMD with PEG
      decreased toxicity of the polymers, while preserving their CXCR4 antagonism.
      Polyplexes prepared with PEG-PAMD inhibited invasion of cancer cells to an extent
      similar to the commercial CXCR4 antagonist Plerixafor. Negative effect of PEG on
      transfection activity of PEG-PAMD polyplexes could be overcome by using
      polyplexes formulated with a mixture of PAMD and PEG-PAMD. CONCLUSION:
      Modification of PAMD with PEG is a viable strategy to preserve the desirable
      CXCR4 antagonism and ability to inhibit cancer cell invasion of PAMD, while
      improving safety and colloidal stability of the PAMD polyplexes.

PMID- 24942538
TI  - Genome-wide mapping of miRNAs expressed in embryonic stem cells and pluripotent
      stem cells generated by different reprogramming strategies.
AB  - BACKGROUND: Reprogrammed cells, including induced pluripotent stem cells (iPSCs)
      and nuclear transfer embryonic stem cells (NT-ESCs), are similar in many respects
      to natural embryonic stem cells (ESCs). However, previous studies have
      demonstrated that iPSCs retain a gene expression signature that is unique from
      that of ESCs, including differences in microRNA (miRNA) expression, while NT-ESCs
      are more faithfully reprogrammed cells and have better developmental potential
      compared with iPSCs. RESULTS: We focused on miRNA expression and explored the
      difference between ESCs and reprogrammed cells, especially ESCs and NT-ESCs. We
      also compared the distinct expression patterns among iPSCs, NT-ESCs and NT-iPSCs.
      The results demonstrated that reprogrammed cells (iPSCs and NT-ESCs) have unique
      miRNA expression patterns compared with ESCs. The comparison of differently
      reprogrammed cells (NT-ESCs, NT-iPSCs and iPSCs) suggests that several miRNAs
      have key roles in the distinct developmental potential of reprogrammed cells.
      CONCLUSIONS: Our data suggest that miRNAs play a part in the difference between
      ESCs and reprogrammed cells, as well as between MEFs and pluripotent cells. The
      variation of miRNA expression in reprogrammed cells derived using different
      reprogramming strategies suggests different characteristics induced by nuclear
      transfer and iPSC generation, as well as different developmental potential among
      NT-ESCs, iPSCs and NT-iPSCs.

PMID- 24942539
TI  - A reflective framework to foster emotionally intelligent leadership in nursing.
AB  - AIM: To propose a reflective framework based on the perspective of emotional
      intelligence (EI) in nurse leadership literature. BACKGROUND: Emotional
      intelligence is a self-development construct aimed at enhancing the management of
      feelings and interpersonal relationships, which has become increasingly popular
      in nurse leadership. Reflection is an established means to foster learning.
      Integrating those aspects of emotional intelligence pertinent to nurse leadership
      into a reflective framework might support the development of nurse leadership in
      a practical context. METHOD: A sample of 22 articles, retrieved via electronic
      databases (Ovid/Medline, BNI, psycArticles, Zetoc and CINAHL) and published
      between January 1996 and April 2009, was analysed in a qualitative descriptive
      content analysis. RESULT: Three dimensions that characterise emotional
      intelligence leadership in the context of nursing - the nurse leader as a 'socio
      cultural architect', as a 'responsive carer' and as a 'strategic visionary' -
      emerged from the analysis. To enable practical application, these dimensions were
      contextualised into a reflective framework. CONCLUSION: Emotional intelligence
      skills are regarded as essential for establishing empowering work environments in
      nursing. A reflective framework might aid the translation of emotional
      intelligence into a real-world context. IMPLICATIONS FOR NURSING PRACTICE: The
      proposed framework may supplement learning about emotional intelligence skills
      and aid the integration of emotional intelligence in a clinical environment.

PMID- 24942541
TI  - Transcriptomic effects of estradiol treatment on cultured human uterine smooth
      muscle cells.
AB  - Contractility of the myometrial smooth muscle cells during the estrous cycle and
      pregnancy is modulated by estrogen but the temporal expression of estrogen
      (relative to progesterone) and the type of contraction involved are distinctly
      different in pregnancy and estrous. This in vitro cell culture study investigated
      the global gene expression profile of human uterine smooth muscle cells (hUtSMCs)
      following 17beta-estradiol (E2) treatment. In response to E2 treatment 540 genes,
      many of which have not been previously described as estrogen responsive, were
      identified as significantly differentially expressed. These genes are involved in
      biological processes that include muscle contraction, cell migration and
      adhesion, apoptosis and phosphorylation. Evidence from this study suggests that
      17beta-estradiol may have effects that are contrary to an overall contraction
      phenotype. The hUtSMC in vitro culture system is a useful model to investigate
      steroid effects on smooth muscle cells and may provide additional clues as to how
      smooth muscle cells behave in vivo.

PMID- 24942540
TI  - Subcutaneous tocilizumab versus placebo in combination with disease-modifying
      antirheumatic drugs in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The efficacy and safety of subcutaneous tocilizumab (TCZ-SC) versus
      subcutaneous placebo (PBO-SC) was evaluated in patients with rheumatoid arthritis
      who had an inadequate response to disease-modifying antirheumatic drugs in the
      BREVACTA study. METHODS: Patients (n = 656) were randomized 2:1 to receive TCZ-SC
      162 mg every other week or PBO-SC every other week for 24 weeks; 20% previously
      received anti-tumor necrosis factor treatment. Escape therapy with TCZ-SC 162 mg
      weekly was offered from week 12 for inadequate response. The primary end point
      was the American College of Rheumatology 20% improvement (ACR20) response at week
      24. The key secondary outcomes were radiographic progression and safety. RESULTS:
      TCZ-SC was superior to PBO-SC for ACR20 response at week 24 (60.9% versus 31.5%;
      P < 0.0001). All secondary end points showed TCZ-SC to be superior to PBO-SC,
      including ACR50 and ACR70 response (40% and 20% for TCZ-SC, respectively, and 12%
      and 5% for PBO-SC, respectively; P < 0.0001 for both) and Disease Activity Score
      in 28 joints (DAS28) remission (DAS28 <2.6; 32% versus 4% [P < 0.0001]). The mean
      change in modified Sharp/van der Heijde score was significantly lower in the TCZ
      SC group than the PBO-SC group (0.62 versus 1.23; P = 0.0149). Adverse events
      (AEs) and serious AEs (SAEs) were comparable between the TCZ-SC and PBO-SC
      groups; 4.6% and 3.7% of patients had at least 1 SAE, respectively, and infection
      was the most common SAE in 2.1% and 1.8% of patients, respectively. More
      injection site reactions occurred with TCZ-SC than PBO-SC (7.1% versus 4.1%). No
      anaphylaxis or serious hypersensitivity reactions occurred. There were 3 deaths
      in the TCZ-SC group and 0 in the PBO-SC group. CONCLUSION: TCZ-SC every other
      week had significantly greater efficacy, including ACR end points and inhibition
      of joint damage, compared with PBO-SC. TCZ-SC was well tolerated and its safety
      profile was comparable with that of previous intravenous TCZ studies.

PMID- 24942543
TI  - Mechanistic investigation of the selective reduction of Meldrum's acids to beta
      hydroxy acids using SmI2 and H2O.
AB  - The mechanism of a recently reported first mono-reduction of cyclic 1,3-diesters
      (Meldrum's acids) to beta-hydroxy acids with SmI2-H2O has been studied using a
      combination of reactivity, deuteration, kinetic isotope and radical clock
      experiments. Most crucially, the data indicate that the reaction proceeds via
      reversible electron transfer and that water, as a ligand for SmI2, stabilizes the
      radical anion intermediate rather than only promoting the first electron transfer
      as originally proposed. 

PMID- 24942542
TI  - Pulmonary epithelioid hemangioendothelioma presenting with vertebral metastases:
      a case report.
AB  - INTRODUCTION: Epithelioid hemangioendothelioma is a rare vascular tumor that has
      an epithelioid and histiocytoid appearance, originates from vascular endothelial
      or pre-endothelial cells and comprises less than 1% of all vascular tumors. It
      was described for the first time in 1975 as pulmonary epithelioid
      hemangioendothelioma, because initially it was believed to be an aggressive form
      of bronchoalveolar cell carcinoma with a remarkable propensity to invade adjacent
      blood vessels and small airways. Only a few cases have been reported in the
      literature to date. Tumor cells expressing Fli-1 and CD31 have been identified as
      relatively specific endothelial markers. Epithelioid hemangioendothelioma may
      affect multiple organs and may vary considerably in its clinical and radiological
      presentation. More than 50% to 76% of pulmonary epithelioid hemangioendothelioma
      patients are asymptomatic. They are usually incidentally diagnosed on the basis
      of abnormal chest radiography during routine physical examinations. Hematologic
      and gastrointestinal disorders and weakness or numbness may also be observed, in
      addition to respiratory symptoms, in cases of disseminated pulmonary epithelioid
      hemangioendothelioma. Pain and swelling, pathological fractures, spine
      compression or paresthesia, loss of muscular strength and paraplegia may be
      present when bone metastases occur. Because of the rarity of this disease, there
      is no standard for treatment. CASE PRESENTATION: A 46-year-old Caucasian woman
      presented to our institution in November 2009 with metastases of pulmonary
      epithelioid hemangioendothelioma from the L3 and L4 vertebrae. A course of
      radiotherapy at a dosage of 3,000 cGy delivered in individual doses of 200
      cGy/day for 5 days/wk to the L3 and L4 vertebrae led to the disappearance of the
      patient's lumbar pain without any detectable side effects. Percussion of the
      patient's vertebral spine was negative, and no radiological progression of bone
      disease was found at her 1-year follow-up examination. CONCLUSION: Since
      epithelioid hemangioendothelioma was first correctly defined, several research
      groups have reported their experiences with epithelioid hemangioendothelioma
      irradiation. Further studies are needed to establish a standard radiation dose to
      be used for such a complex and extremely rare disease. In our present case, a
      radiotherapy dosage of 3,000 cGy delivered in individual doses 200 cGy/day for 5
      days/wk allowed us to reach our goals: local pain control with good tolerance and
      better quality of life by the 1-year follow-up examination.

PMID- 24942544
TI  - Group I metabotropic glutamate receptor mediated dynamic immune dysfunction in
      children with fragile X syndrome.
AB  - BACKGROUND: Fragile X syndrome (FXS) is the leading cause of inheritable
      intellectual disability in male children, and is predominantly caused by a single
      gene mutation resulting in expanded trinucleotide CGG-repeats within the 5'
      untranslated region of the fragile X mental retardation (FMR1) gene. Reports have
      suggested the presence of immune dysregulation in FXS with evidence of altered
      plasma cytokine levels; however, no studies have directly assessed functional
      cellular immune responses in children with FXS. In order to ascertain if immune
      dysregulation is present in children with FXS, dynamic cellular responses to
      immune stimulation were examined. METHODS: Peripheral blood mononuclear cells
      (PBMC) were from male children with FXS (n=27) and from male aged-matched
      typically developing (TD) controls (n=8). PBMC were cultured for 48 hours in
      media alone or with lipopolysaccharides (LPS; 1 MUg/mL) to stimulate the innate
      immune response or with phytohemagglutinin (PHA; 8 MUg/mL) to stimulate the
      adaptive T-cell response. Additionally, the group I mGluR agonist, DHPG, was
      added to cultures to ascertain the role of mGluR signaling in the immune response
      in subject with FXS. Supernatants were harvested and cytokine levels were
      assessed using Luminex multiplexing technology. RESULTS: Children with FXS
      displayed similar innate immune response following challenge with LPS alone when
      compared with TD controls; however, when LPS was added in the presence of a group
      I mGluR agonist, DHPG, increased immune response were observed in children with
      FXS for a number of pro-inflammatory cytokines including IL-6 (P=0.02), and IL
      12p40 (P<0.01). Following PHA stimulation, with or without DHPG, no significant
      differences between subjects with FXS and TD were seen. CONCLUSIONS: In
      unstimulated cultures, subjects with FXS did not display altered dynamic immune
      response to LPS or PHA alone; however, subjects with FXS showed an altered
      response to co-current stimulation of LPS and DHPG, such that subjects with FXS
      failed to inhibit production of pro-inflammatory cytokines, suggesting a role of
      group I mGluR signaling in innate immune responses in FXS.

PMID- 24942547
TI  - Mesenchymal stromal cells uptake and release paclitaxel without reducing its
      anticancer activity.
AB  - To improve the drug delivery efficiency on target cells, many strategies have
      been developed including Mesenchymal Stromal Cells (MSCs) approaches. In a
      previous study, we found that bone-marrow-derived MSCs (BM-MSCs) were able to
      incorporate and release the anti-tumor and anti-angiogenic drug, Paclitaxel
      (PTX). In this study, we evaluated the stability of PTX in standard cell culture
      conditions by analyzing the metabolites produced by MSCs after their
      incorporation of the drug. We are able to show that MSCs do not release either 3
      OH-PTX or 6-OH-PTX metabolites (having a lower anticancer activity) but release
      an active PTX molecule together with the isomer 7-Epitaxol, is known to maintain
      the whole biological activity. This confirms that the simple procedure of MSCs
      priming with a drug (without any genetic cell manipulation), in our case PTX,
      does not modify the activity of the molecule and provides a new biological-device
      to carry and deliver PTX in tumor sites, by contributing to improve drug efficacy
      and target selectivity in cancer therapy.

PMID- 24942546
TI  - Mutation of praR in Rhizobium leguminosarum enhances root biofilms, improving
      nodulation competitiveness by increased expression of attachment proteins.
AB  - In Rhizobium leguminosarum bv. viciae, quorum-sensing is regulated by CinR, which
      induces the cinIS operon. CinI synthesizes an AHL, whereas CinS inactivates PraR,
      a repressor. Mutation of praR enhanced biofilms in vitro. We developed a light
      (lux)-dependent assay of rhizobial attachment to roots and demonstrated that
      mutation of praR increased biofilms on pea roots. The praR mutant out-competed
      wild-type for infection of pea nodules in mixed inoculations. Analysis of gene
      expression by microarrays and promoter fusions revealed that PraR represses its
      own transcription and mutation of praR increased expression of several genes
      including those encoding secreted proteins (the adhesins RapA2, RapB and RapC,
      two cadherins and the glycanase PlyB), the polysaccharide regulator RosR, and
      another protein similar to PraR. PraR bound to the promoters of several of these
      genes indicating direct repression. Mutations in rapA2, rapB, rapC, plyB, the
      cadherins or rosR did not affect the enhanced root attachment or nodule
      competitiveness of the praR mutant. However combinations of mutations in rapA,
      rapB and rapC abolished the enhanced attachment and nodule competitiveness. We
      conclude that relief of PraR-mediated repression determines a lifestyle switch
      allowing the expression of genes that are important for biofilm formation on
      roots and the subsequent initiation of infection of legume roots. 

PMID- 24942548
TI  - A steroidal Na+/K+ ATPase inhibitor triggers pro-apoptotic signaling and induces
      apoptosis in prostate and lung tumor cells.
AB  - Recently we have reported potent anti-cancer actions of various steroidal
      Na(+)/K(+) ATPase inhibitors in multiple cell lines. Furthermore, the most
      powerful compound identified in this study, the 3-[(R)-3-pyrrolidinyl]oxime
      derivative (3-R-POD), was highly effective in various tumor cell lines in vitro,
      and exhibited significant tumor growth inhibition in prostate and lung xenografts
      in vivo. In the present study we have addressed the molecular mechanisms
      implicated in the anti-cancer actions of 3-R-POD. We report here that 3-R-POD
      induces strong apoptotic responses in A549 lung- and in DU145 prostate- cancer
      cells. These effects are accompanied by significant upregulation of caspase-3
      activity. Focussing on A549 cells, we further demonstrate late downregulation of
      BCL-2- and upregulation of c-Fos- gene transcription. In addition, the steroidal
      Na(+)/K(+) ATPase inhibitor induced late de-phosphorylation of Focal Adhesion
      Kinase (FAK) and activation of p38 MAPK. Our findings suggest that the steroidal
      Na(+)/K(+) ATPase inhibitor 3-R-POD induces apoptosis, paralleled by altered BCL
      2 and c-Fos gene transcription, inhibition of the pro-survival FAK signalling, up
      regulation of the pro-apoptotic p38 MAPK pathway and stimulation of caspase-3
      activity. 

PMID- 24942545
TI  - Human papillomavirus detection in women with and without human immunodeficiency
      virus infection in Colombia.
AB  - BACKGROUND: HIV infection leads to a decreasing immune response, thereby
      facilitating the appearance of other infections, one of the most important ones
      being HPV. However, studies are needed for determining associations between
      immunodeficiency caused by HIV and/or the presence of HPV during the course of
      cervical lesions and their degree of malignancy. This study describes the
      cytological findings revealed by the Papanicolaou test, laboratory
      characteristics and HPV molecular profile in women with and without HIV
      infection. METHODS: A total of 216 HIV-positive and 1,159 HIV-negative women were
      invited to participate in the study; PCR was used for the molecular detection of
      HPV in cervical samples. Statistical analysis (such as percentages, Chi-square
      test and Fisher's exact test when applicable) determined human papillomavirus
      (HPV) infection frequency (single and multiple) and the distribution of six types
      of high-risk-HPV in women with and without HIV infection. Likewise, a logistic
      regression model was run to evaluate the relationship between HIV-HPV infection
      and different risk factors. RESULTS: An association was found between the
      frequency of HPV infection and infection involving 2 or more HPV types (also
      known as multiple HPV infection) in HIV-positive women (69.0% and 54.2%,
      respectively); such frequency was greater than that found in HIV-negative women
      (44.3% and 22.7%, respectively). Statistically significant differences were
      observed between both groups (p = 0.001) regarding HPV presence (both in
      infection and multiple HPV infection). HPV-16 was the most prevalent type in the
      population being studied (p = 0.001); other viral types had variable distribution
      in both groups (HIV-positive and HIV-negative). HPV detection was associated with
      <500 cell/mm(3) CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV
      DNA detection, <200 cell/mm(3) CD4-count (p = 0.001), and higher HIV-viral-load
      (p = 0.001) were associated with abnormal cytological findings. CONCLUSIONS: The
      HIV-1 positive population in this study had high multiple HPV infection
      prevalence. The results for this population group also suggested a greater
      association between HPV-DNA presence and cytological findings. HPV detection,
      together with low CD4 count, could represent useful tools for identifying HIV
      positive women at risk of developing cervical lesions.

PMID- 24942550
TI  - Investigating RET RTK signaling pathways using an IAP-based activity-profiling
      approach.
AB  - Many neurodegenerative diseases, such as Parkinson's disease, can be directly
      correlated with the deregulation in neuronal signaling. Hence, it is
      indispensable for therapy development to understand the participating signaling
      processes. Because the activity of the involved protein kinases is of major
      interest for the investigation of these signaling processes, an affinity-based
      chemical proteomics approach that allows for the activity profiling of protein
      kinases was developed within this study. This approach was applied to investigate
      the RET9 receptor tyrosine kinase signaling pathway that plays a central role in
      neuronal signaling. In addition to already known RET9 downstream targets, several
      other protein kinases were found to be highly activated upon RET9 stimulation. 

PMID- 24942552
TI  - The impact of a 'Critical Moments' workshop on undergraduate nursing students'
      attitudes to caring for patients at the end of life: an evaluation.
AB  - AIMS AND OBJECTIVES: To evaluate the impact of an educational workshop on nursing
      students' attitudes to caring for dying patients. BACKGROUND: The quality of end
      of-life care education provided in preregistration nursing programmes has been
      criticised. The lack of attention to the emotional content results in nursing
      students feeling ill-prepared to care for the dying and bereaved. This article
      reports the findings of a study conducted to evaluate the impact of an
      educational workshop on undergraduate nursing students' attitudes to caring for
      patients at the end of life. DESIGN: A pre- and postintervention survey was used
      to determine nursing students' attitudes and feelings concerning end-of-life care
      prior to and following their involvement in an educational workshop. METHODS:
      Third-year undergraduate nursing students completed two questionnaires
      incorporating the Frommelt Attitude Toward Care of the Dying Scale, before and
      after attending a 'Critical Moments' workshop. RESULTS: The data revealed a
      statistically significant increase in positive attitudes to end-of-life care
      amongst the respondents. Free text responses confirmed the development of
      positive attitudes and indicated that the workshop was regarded as a valuable
      learning opportunity. CONCLUSIONS: Workshops that use case studies based on 'real
      life' episodes of end-of-life care can provide an effective learning opportunity
      that significantly improves the attitudes of nursing students to caring for the
      dying. RELEVANCE TO CLINICAL PRACTICE: Identifying emotional labour is an
      important stage in the development of emotionally intelligent nurses. It may
      reduce the risk of occupational stress, burnout and potential withdrawal from
      nursing practice in the longer term. Timing, expert facilitation and peer support
      are important considerations for an educational workshop that aims to enable
      nurses to remain healthy whilst delivering high-quality care to patients and
      their relatives near the end of life.

PMID- 24942549
TI  - Hippocampal surface deformation accuracy in T1-weighted volumetric MRI sequences
      in subjects with epilepsy.
AB  - BACKGROUND AND PURPOSE: To demonstrate the accuracy across different acquisition
      and analysis methods, we evaluated the variability in hippocampal volumetric and
      surface displacement measurements resulting from two different MRI (magnetic
      resonance imaging) acquisition protocols. METHODS: Nine epilepsy patients
      underwent two independent T1-weighted magnetization prepared spoiled gradient
      sequences during a single 3T MRI session. Using high-dimension mapping-large
      deformation (HDM-LD) segmentation, we calculated volumetric estimates and
      generated a vector-based 3-dimensional surface model of each subject's
      hippocampi, and evaluated volume and surface changes, the latter using a cluster
      based noise estimation model. RESULTS: Mean hippocampal volumes and standard
      deviations for the left hippocampi were 2,750 (826) mm3 and 2,782 (859) mm3 (P =
      .13), and for the right hippocampi were 2,558 (750) mm3 and 2,547 (692) mm3 (P =
      .76), respectively for the MPR1 and MPR2 sequences. Average Dice coefficient
      comparing overlap for segmentations was 86%. There was no significant effect of
      MRI sequence on volume estimates and no significant hippocampal surface change
      between sequences. CONCLUSION: Statistical comparison of hippocampal volumes and
      statistically thresholded HDM-LD surfaces in TLE patients showed no differences
      between the segmentations obtained in the two MRI acquisition sequences. This
      validates the robustness across MRI sequences of the HDM-LD technique for
      estimating volume and surface changes in subjects with epilepsy.

PMID- 24942553
TI  - N-3 PUFA increase bioavailability and function of endothelial progenitor cells.
AB  - BACKGROUND AND AIMS: Recent data suggest that n-3 PUFA exert beneficial effects
      on endothelial progenitor cell (EPC) biology. We sought to investigate whether
      these effects might be mediated by enhanced EPC in vitro function and/or in vivo
      bioavailability. METHODS AND RESULTS: CACs and late-outgrowth EPCs were isolated
      from peripheral blood mononuclear cells obtained from 12 donor buffy-coats. The
      effect of n-3 PUFA (EPA:DHA = 0.9:1.5; 9 MUM EPA plus 15 MUM DHA) was tested on
      CAC/EPC viability, function (tube-formation) and pro-inflammatory molecule
      expression. Circulating EPC (cells positive for CD34, CD133 and kinase insert
      domain receptor - KDR cell-surface antigens by flow cytometry) number was
      evaluated in 20 healthy subjects (10 F/10 M, 32 +/- 5 years), randomized to
      receive 4 mackerel or sardine portions per week for 6 weeks followed by a 6 week
      free-diet period. N-3 PUFA improved CAC and late-outgrowth EPC viability (p <
      0.05) and the capacity to form tube-like structures in CACs (+38%; p < 0.05) and
      late-outgrowth EPCs (+15%; p < 0.05). ICAM-1 expression was reduced in both CACs
      (p < 0.05) and late-outgrowth EPCs (p < 0.05) and VCAM-1 in late-outgrowth EPCs
      (p < 0.005). N-3 PUFA significantly decreased TNF-alpha and MCP-1 expression in
      CACs and IL-8, TNF-alpha and MCP-1 in late-outgrowth EPCs (p < 0.05). Circulating
      EPC number significantly improved after 6 weeks of a fish-enriched diet (p <
      0.01) and returned to baseline levels after a 6 week free-diet period (p < 0.01).
      Plasma EPA levels were independently and positively associated with EPC levels (p
      < 0.005). CONCLUSION: Our findings support the case of a beneficiary role played
      by n-3 PUFA in EPC function and bioavailability.

PMID- 24942554
TI  - An investigation of indomethacin-nicotinamide cocrystal formation induced by
      thermal stress in the solid or liquid state.
AB  - The impact of thermal stress on indomethacin (IMC)-nicotinamide (NIC) cocrystal
      formation with or without neat cogrinding was investigated using differential
      scanning calorimetry (DSC), Fourier transform infrared (FTIR) microspectroscopy,
      and simultaneous DSC-FTIR microspectroscopy in the solid or liquid state.
      Different evaporation methods for preparing IMC-NIC cocrystals were also
      compared. The results indicated that even after cogrinding for 40 min, the FTIR
      spectra for all IMC-NIC ground mixtures were superimposable on the FTIR spectra
      of IMC and NIC components, suggesting there was no cocrystal formation between
      IMC and NIC after cogrinding. However, these IMC-NIC ground mixtures appear to
      easily undergo cocrystal formation after the application of DSC determination.
      Under thermal stress induced by DSC, the amount of cocrystal formation increased
      with increasing cogrinding time. Moreover, simultaneous DSC-FTIR
      microspectroscopy was a useful one-step technique to induce and clarify the
      thermal-induced stepwise mechanism of IMC-NIC cocrystal formation from the ground
      mixture in real time. Different solvent evaporation rates induced by thermal
      stress significantly influenced IMC-NIC cocrystal formation in the liquid state.
      In particular, microwave heating may promote IMC-NIC cocrystal formation in a
      short time.

PMID- 24942555
TI  - Social networks of health care providers and patients in cardiovascular risk
      management: a study protocol.
AB  - BACKGROUND: In recent years, preventive and clinical interventions for
      cardiovascular risk management have been implemented widely in primary care in
      the Netherlands. Although this has enhanced quality and outcomes of
      cardiovascular risk management, further improvement remains possible. In the
      planned observational study, we aim to examine the role of social networks of
      healthcare providers and patients in quality and outcomes of cardiovascular risk
      management. METHODS/DESIGN: In a longitudinal observational study, data on social
      networks of approximately 300 primary care providers from 30 general practices
      and 900 cardiovascular patients will be collected twice, with a six month
      interval, using a mix of measures. Social networks are documented with
      specifically designed questionnaires for patients, relatives, and healthcare
      professionals. For each included patient, we will extract from medical records to
      gather data on clinical processes and cardiovascular risk predictors. Data on
      self-management and psychosocial outcomes of patients will be collected using
      questionnaires for patients. The analysis focuses on identifying network
      characteristics, which are associated with (changes in) cardiovascular risk
      management or self-management. DISCUSSION: This research will provide insight
      into the role of social networks of patients and providers in cardiovascular risk
      management in primary practice. TRIAL REGISTRATION: Nederlands Trial Register
      NTR4069.

PMID- 24942557
TI  - Precarious employment and the risk of serious psychological distress: a
      population-based cohort study in Japan.
AB  - OBJECTIVES: This study examines whether precarious employment increases the risk
      of serious psychological distress (SPD) in a nationally representative cohort of
      Japanese middle-aged people. METHODS: From 2005-2009, we followed 8486 male and
      6736 female participants (aged 50-59 years) in the Longitudinal Survey of Middle
      aged and Elderly Persons. All individuals were employed and free of SPD,
      cardiovascular disease, and cancer at baseline. The participants were classified
      into two groups based on their baseline employment contract: precarious and full
      time permanent work. SPD was assessed at each year during the study, using the K6
      scale, a self-rated 6-item scale that screens for mood or anxiety disorders. We
      used discrete-time survival analysis, with a complementary log-log link, to
      examine the effect of precarious employment on SPD incidence. RESULTS: During a
      maximum follow-up period of four years, 374 men and 364 women developed SPD. Male
      precarious employees were more likely to develop SPD than male full-time
      permanent employees (hazard ratio 1.79, 95% confidence interval 1.28-2.51) in the
      full model, after adjusting for sociodemographic and occupational factors,
      cardiovascular disease risk, and K6 scores at baseline. By contrast, no
      significant association was observed among female employees. However, an analysis
      stratified by marital status revealed an association similar to that found among
      men but only among unmarried women. CONCLUSIONS: The findings suggest that
      precarious employment is associated with double the risk of SPD incidence among
      middle-aged Japanese men and - when stratified by marital status - among
      unmarried women. This highlights a major gender difference in the association
      between precarious employment and risk of SPD.

PMID- 24942556
TI  - Multiple primary acral melanomas in two young caucasian patients.
AB  - BACKGROUND: Acral melanoma (AM) is still one of the most poorly studied
      melanomas. It generally presents beyond the fifth decade of life and usually is a
      BRAF wild-type melanoma. OBJECTIVE: To report the first cases of multiple primary
      AM in Caucasians. METHODS: Clinical, dermoscopic, pathological and molecular
      profiles. RESULTS: A healthy 34- year-old male presented an in situ subungual
      melanoma on his finger, and 22 months later a fast-growing nodular melanoma
      appeared in an existing nevus on the sole. Both melanomas carried the V600E BRAF
      mutation. A 19-year-old female patient presented 2 in situ melanomas on different
      parts of her left foot within a 6-year period of time. The patients have neither
      familiar melanoma nor germline mutations in CDKN2A/CDK4 genes. CONCLUSION:
      Multiple AM in Caucasians is very rare. BRAF mutations are possible, especially
      in a high-risk set of patients with multiple nevi. Specific acral examination
      must be recommended since AM still suffers delayed detection.

PMID- 24942559
TI  - Electrocatalysis.

PMID- 24942558
TI  - Monkey alcohol tissue research resource: banking tissues for alcohol research.
AB  - BACKGROUND: An estimated 18 million adults in the United States meet the clinical
      criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the
      third leading cause of preventable death. In addition to brain pathology, heavy
      alcohol consumption is comorbid with damage to major organs including heart,
      lungs, liver, pancreas, and kidneys. Much of what is known about risk for and
      consequences of heavy consumption derive from rodent or retrospective human
      studies. The neurobiological effects of chronic intake in rodent studies may not
      easily translate to humans due to key differences in brain structure and
      organization between species, including a lack of higher-order cognitive
      functions, and differences in underlying prefrontal cortical neural structures
      that characterize the primate brain. Further, rodents do not voluntarily consume
      large quantities of ethanol (EtOH) and they metabolize it more rapidly than
      primates. METHODS: The basis of the Monkey Alcohol Tissue Research Resource
      (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking
      excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over
      long periods of time (12 to 30 months) with concomitant pathological changes in
      endocrine, hepatic, and central nervous system (CNS) processes. The patterns and
      range of alcohol intake that monkeys voluntarily consume parallel what is
      observed in humans with alcohol use disorders and the longitudinal experimental
      design spans stages of drinking from the EtOH-naive state to early exposure
      through chronic abuse. Age- and sex-matched control animals self-administer an
      isocaloric solution under identical operant procedures. RESULTS: The MATRR is a
      unique postmortem tissue bank that provides CNS and peripheral tissues, and
      associated bioinformatics from monkeys that self-administer EtOH using a
      standardized experimental paradigm to the broader alcohol research community.
      CONCLUSIONS: This resource provides a translational platform from which we can
      better understand the disease processes associated with alcoholism.

PMID- 24942560
TI  - A unifying mechanism for the rearrangement of vinyl allene oxide geometric
      isomers to cyclopentenones.
AB  - A new mechanism for the rearrangement of vinyl allene oxide geometric isomers to
      stereodefined cyclopentenones is proposed based on DFT computations. This
      mechanism comprises two steps, first the ring opening of the oxirane to give a
      vinylcyclopropanone, and then a [1,3]-C sigmatropic rearrangement. Depending
      primarily on the allene oxide double bond geometry the stepwise pathway is either
      competitive (for E allene oxides) or favored (for Z allene oxides) relative to
      the already described SN2-like concerted pathway. All bond-forming reactions take
      place through helically chiral transition states, which allows the stereochemical
      information of the substrates to be transferred to that of the products, in
      particular in the case of (enantiopure) Z allene oxides. In addition to revealing
      one more of the fascinating mechanisms with memory of chirality, the results
      deepen our understanding of the important jasmonate and clavulone biosynthetic
      pathways that occur in plants and corals. 

PMID- 24942561
TI  - FGF-23 dysregulates calcium homeostasis and electrophysiological properties in HL
      1 atrial cells.
AB  - BACKGROUND: Fibroblast growth factor (FGF)-23 is a key regulator of phosphate
      homeostasis. Higher FGF-23 levels are correlated with poor outcomes in
      cardiovascular diseases. FGF-23 can produce cardiac hypertrophy and increase
      intracellular calcium, which can change cardiac electrical activity. However, it
      is not clear whether FGF-23 possesses arrhythmogenic potential through calcium
      dysregulation. Therefore, the purposes of this study were to evaluate the
      electrophysiological effects of FGF-23 and identify the underlying mechanisms.
      METHODS: Patch clamp, confocal microscope with Fluo-4 fluorescence, and Western
      blot analyses were used to evaluate the electrophysiological characteristics,
      calcium homeostasis and calcium regulatory proteins in HL-1 atrial myocytes with
      and without FGF-23 (10 and 25 ng/mL) incubation for 24 h. RESULTS: FGF-23 (25
      ng/mL) increased L-type calcium currents, calcium transient and sarcoplasmic
      reticulum Ca(2+) contents in HL-1 cells. FGF-23 (25 ng/mL)-treated cells (n = 14)
      had greater incidences (57%, 17% and 15%, P < 0.05) of delayed
      afterdepolarizations than control (n = 12) and FGF-23 (10 ng/mL)-treated cells (n
      = 13). Compared with control cells, FGF-23 (25 ng/mL)-treated cells (n = 14)
      exhibited increased phosphorylation of calcium/calmodulin-dependent protein
      kinase IIdelta and phospholamban (PLB) at threonine 17 but had similar
      phosphorylation extents of PLB at serine 16, total PLB and sarcoplasmic reticulum
      Ca(2+) -ATPase protein. Moreover, the FGF receptor inhibitor (PD173074, 10 nM),
      calmodulin inhibitor (W7, 5 MUM) and phospholipase C inhibitor (U73122, 1 MUM)
      attenuated the effects of FGF-23 on calcium/calmodulin-dependent protein kinase
      II phosphorylation. CONCLUSIONS: FGF-23 increases HL-1 cells arrhythmogenesis
      with calcium dysregulation through modulating calcium-handling proteins.

PMID- 24942565
TI  - Elasticity of grossular-andradite solid solution: an ab initio investigation.
AB  - Grossular and andradite are garnet end-members stable under upper mantle
      conditions. We perform ab initio simulations to investigate the dependence of the
      bulk modulus on chemical composition of the grossular-andradite solid solution,
      Ca3Fe(2-2x)Al(2x)(SiO4)3. All-electron local basis sets of Gaussian-type orbitals
      and the hybrid B3LYP density functional are used. Our calculations predict a
      linear modulus-composition trend, in contrast to previous conjectures based on
      "heterogeneous" experimental measurements. We estimate the largest deviation from
      linearity to be about 0.5 GPa under ambient conditions, and to progressively
      reduce to less than 0.2 GPa at pressure P = 20 GPa. The bulk modulus is computed
      over the whole composition range 0 <=x<= 1 following two independent approaches:
      fitting energy-volume data to an equation-of-state and calculating elastic
      tensors. Results from the two methods are in perfect agreement, assuring
      consistency and high numerical accuracy of the adopted algorithms.

PMID- 24942563
TI  - Extracorporeal shockwave therapy in the treatment of erectile dysfunction: a
      prospective, randomized, double-blinded, placebo controlled study.
AB  - OBJECTIVES: To investigate the role of low-intensity extracorporeal shockwave
      therapy in the treatment of erectile dysfunction. METHODS: This was a double
      blinded, single-center, prospective, randomized, placebo-controlled trial. After
      a 2-week phosphodiesterase type 5 inhibitor washout period, patients were
      assessed with Sexual Health Inventory for Men, International Index of Erectile
      Function-ED domain scores and Erection Hardness Score. Randomization into either
      the low-intensity extracorporeal shockwave therapy group or the sham group took
      place. After the 9-week treatment period, patients were followed up 4 weeks
      later. Follow-up assessment was in the form of International Index of Erectile
      Function-ED domain score and Erection Hardness Score. RESULTS: A total of 70
      patients were recruited into the study, 58 patients completed the study. A total
      of 28 patients were randomized into the sham therapy arm, and 30 patients were
      randomized into the low-intensity extracorporeal shockwave therapy arm. There was
      no significant difference between these two groups in baseline International
      Index of Erectile Function-ED domain score and Erection Hardness Score. The mean
      International Index of Erectile Function-ED domain score of the low-intensity
      extracorporeal shockwave therapy arm and sham arm in week 13 were 17.8 +/- 4.8
      and 15.8 +/- 6.1, respectively (P = 0.156). The mean Erection Hardness Scores in
      week 13 were 2.7 +/- 0.5 and 2.4 +/- 0.9, respectively (P = 0.163). When patients
      were stratified into different baseline Sexual Health Inventory for Men
      subgroups, the pre-intervention and post-intervention difference in low-intensity
      extracorporeal shockwave therapy was found to be significant in the subgroup with
      severe erectile dysfunction (low-intensity extracorporeal shockwave therapy
      International Index of Erectile Function-ED domain improvement: 10.1 +/- 4.1 vs
      sham therapy International Index of Erectile Function-ED domain improvement: 3.2
      +/- 3.3; P = 0.003). CONCLUSION: The present trial shows the tolerability and
      clinical efficacy of low-intensity extracorporeal shockwave therapy in a subgroup
      of patients with erectile dysfunction.

PMID- 24942562
TI  - Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common
      humoral immune responses among patients.
AB  - Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by
      autoantibodies (autoAbs) against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3
      antibodies (Abs) from four PV patients and identify pathogenic VH1-46 autoAbs
      from all four patients. Unexpectedly, VH1-46 autoAbs had relatively few
      replacement mutations. We reverted antibody somatic mutations to their germline
      sequences to determine the requirement of mutations for autoreactivity. Three of
      five VH1-46 germline-reverted Abs maintain Dsg3 binding, compared with zero of
      five non-VH1-46 germline-reverted Abs. Site-directed mutagenesis of VH1-46 Abs
      demonstrates that acidic amino-acid residues introduced by somatic mutation or
      heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our
      data suggest that VH1-46 autoantibody gene usage is commonly found in PV because
      VH1-46 Abs require few to no mutations to acquire Dsg3 autoreactivity, which may
      favour their early selection. Common VH gene usage indicates common humoral
      immune responses, even among unrelated patients. 

PMID- 24942564
TI  - The ZInEP Epidemiology Survey: background, design and methods.
AB  - This article introduces the design, sampling, field procedures and instruments
      used in the ZInEP Epidemiology Survey. This survey is one of six ZInEP projects
      (Zurcher Impulsprogramm zur nachhaltigen Entwicklung der Psychiatrie, i.e. the
      "Zurich Program for Sustainable Development of Mental Health Services"). It
      parallels the longitudinal Zurich Study with a sample comparable in age and
      gender, and with similar methodology, including identical instruments. Thus, it
      is aimed at assessing the change of prevalence rates of common mental disorders
      and the use of professional help and psychiatric sevices. Moreover, the current
      survey widens the spectrum of topics by including sociopsychiatric questionnaires
      on stigma, stress related biological measures such as load and cortisol levels,
      electroencephalographic (EEG) and near-infrared spectroscopy (NIRS) examinations
      with various paradigms, and sociophysiological tests. The structure of the ZInEP
      Epidemiology Survey entails four subprojects: a short telephone screening using
      the SCL-27 (n of nearly 10,000), a comprehensive face-to-face interview based on
      the SPIKE (Structured Psychopathological Interview and Rating of the Social
      Consequences for Epidemiology: the main instrument of the Zurich Study) with a
      stratified sample (n = 1500), tests in the Center for Neurophysiology and
      Sociophysiology (n = 227), and a prospective study with up to three follow-up
      interviews and further measures (n = 157). In sum, the four subprojects of the
      ZInEP Epidemiology Survey deliver a large interdisciplinary database.

PMID- 24942566
TI  - Promoting our understanding of neural plasticity by exploring developmental
      plasticity in early and adult life.
AB  - Developmental plasticity (DP) is widely considered to be a property of early life
      stages, but evidence suggests it can be reactivated in mature brains. For
      example, recent developments on animal models suggest that experience in enriched
      environments (EE) can induce DP and enable adult recovery from amblyopia; even
      when the typical critical period for that recovery has closed. An interesting
      body of evidence suggests that extrapolation of the rejuvenatory power of that
      paradigm in mature human brains is feasible. These studies show that exposure to
      EE throughout life is associated with a delay, or even prevention, of age-related
      cognitive deficits. Consequently, it can be concluded that DP might underlie the
      neuroprotective effects against a neurocognitive breakdown that have been
      observed, and that EE exposure later in life might induce DP in a similar way to
      early EE exposure. Thus, the DP might exert its influence beyond the typical
      developing age ranges: childhood and adolescence. Although further research is
      still required, the observation of EE related neuroprotective effects are a
      breakthrough in the study of DP in humans and new advances in our understanding
      of neural plasticity have thus been reached. 

PMID- 24942567
TI  - Isolation and characterization of a novel alphaherpesvirus in fruit bats.
AB  - Bats are known to harbor emerging RNA viruses. Recent studies have used high
      throughput sequencing technology to identify various virus species, including DNA
      viruses that are harbored by bats; however, little is known about the nature of
      these potentially novel viruses. Here, we report the characterization of a novel
      herpesvirus isolated from an Indonesian pteropodid bat. The virus, tentatively
      named fruit bat alphaherpesvirus 1 (FBAHV1), has a double-stranded DNA genome of
      149,459 bp. The phylogenetic analyses suggested that FBAHV1 is phylogenetically
      grouped with simplexviruses within the subfamily Alphaherpesvirinae. Inoculation
      of FBAHV1 into laboratory mice caused a lethal infection. Virus infection was
      observed in lung, liver, and brain tissue. Serological and PCR screening revealed
      that fruit bats infected with FBAHV1 or its related virus are widely distributed
      in Indonesia. The identification of FBAHV1 makes a considerable contribution to
      our understanding of simplexviruses associated with bats. IMPORTANCE: Bats are
      known to harbor emerging viruses, such as lyssaviruses, henipaviruses, severe
      acute respiratory syndrome-like coronaviruses, and filoviruses. Although
      alphaherpesviruses are disseminated in humans and other animals, there is little
      information about their distribution in bats. Here, we isolated a previously
      unknown alphaherpesvirus from an Indonesian fruit bat. Genome sequence analysis
      suggested that the virus is a member of the genus Simplexvirus within the
      subfamily Alphaherpesvirinae, which also includes common human viruses, such as
      herpes simplex virus 1 and herpes simplex virus 2. FBAHV1 is the first bat
      derived alphaherpesvirus whose complete genome has been sequenced.

PMID- 24942568
TI  - Immune activation is associated with CD8 T cell interleukin-21 production in HIV
      1-infected individuals.
AB  - Interleukin-21 (IL-21) can be produced by CD8 T cells from HIV-1-infected
      individuals and those with autoimmune disease, but the mechanism remains poorly
      understood. Here we demonstrate that IL-21-producing CD8 T cells are not
      associated with CD4 depletion and are absent in patients with idiopathic CD4
      lymphocytopenia. Instead, IL-21 production by CD8 T cells was associated with
      high levels of activation, suggesting that these cells emerge as a consequence of
      excessive chronic immune activation rather than CD4 lymphopenia. 

PMID- 24942569
TI  - Ebola virus modulates transforming growth factor beta signaling and cellular
      markers of mesenchyme-like transition in hepatocytes.
AB  - Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman
      primates, with a median case fatality rate of 78.4%. Although EBOV is considered
      a public health concern, there is a relative paucity of information regarding the
      modulation of the functional host response during infection. We employed temporal
      kinome analysis to investigate the relative early, intermediate, and late host
      kinome responses to EBOV infection in human hepatocytes. Pathway
      overrepresentation analysis and functional network analysis of kinome data
      revealed that transforming growth factor (TGF-beta)-mediated signaling responses
      were temporally modulated in response to EBOV infection. Upregulation of TGF-beta
      signaling in the kinome data sets correlated with the upregulation of TGF-beta
      secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-beta
      signaling, or additional cell receptors and downstream signaling pathway
      intermediates identified from our kinome analysis, also inhibited EBOV
      replication. Further, the inhibition of select cell signaling intermediates
      identified from our kinome analysis provided partial protection in a lethal model
      of EBOV infection. To gain perspective on the cellular consequence of TGF-beta
      signaling modulation during EBOV infection, we assessed cellular markers
      associated with upregulation of TGF-beta signaling. We observed upregulation of
      matrix metalloproteinase 9, N-cadherin, and fibronectin expression with
      concomitant reductions in the expression of E-cadherin and claudin-1, responses
      that are standard characteristics of an epithelium-to-mesenchyme-like transition.
      Additionally, we identified phosphorylation events downstream of TGF-beta that
      may contribute to this process. From these observations, we propose a model for a
      broader role of TGF-beta-mediated signaling responses in the pathogenesis of
      Ebola virus disease. IMPORTANCE: Ebola virus (EBOV), formerly Zaire ebolavirus,
      causes a severe hemorrhagic disease in humans and nonhuman primates and is the
      most lethal Ebola virus species, with case fatality rates of up to 90%. Although
      EBOV is considered a worldwide concern, many questions remain regarding EBOV
      molecular pathogenesis. As it is appreciated that many cellular processes are
      regulated through kinase-mediated phosphorylation events, we employed temporal
      kinome analysis to investigate the functional responses of human hepatocytes to
      EBOV infection. Administration of kinase inhibitors targeting signaling pathway
      intermediates identified in our kinome analysis inhibited viral replication in
      vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also
      demonstrated that EBOV infection modulated TGF-beta-mediated signaling responses
      and promoted "mesenchyme-like" phenotypic changes. Taken together, these results
      demonstrated that EBOV infection specifically modulates TGF-beta-mediated
      signaling responses in epithelial cells and may have broader implications in EBOV
      pathogenesis.

PMID- 24942570
TI  - Analysis of human rotaviruses from a single location over an 18-year time span
      suggests that protein coadaption influences gene constellations.
AB  - Rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses that cause severe
      gastroenteritis in children. In addition to an error-prone genome replication
      mechanism, RVs can increase their genetic diversity by reassorting genes during
      host coinfection. Such exchanges allow RVs to acquire advantageous genes and
      adapt in the face of selective pressures. However, reassortment may also impose
      fitness costs if it unlinks genes/proteins that have accumulated compensatory,
      coadaptive mutations and that operate best when kept together. To better
      understand human RV evolutionary dynamics, we analyzed the genome sequences of
      135 strains (genotype G1/G3/G4-P[8]-I1-C1-R1-A1-N1-T1-E1-H1) that were collected
      at a single location in Washington, DC, during the years 1974 to 1991.
      Intragenotypic phylogenetic trees were constructed for each viral gene using the
      nucleotide sequences, thereby defining novel allele level gene constellations
      (GCs) and illuminating putative reassortment events. The results showed that RVs
      with distinct GCs cocirculated during the vast majority of the collection years
      and that some of these GCs persisted in the community unchanged by reassortment.
      To investigate the influence of protein coadaptation on GC maintenance, we
      performed a mutual information-based analysis of the concatenated amino acid
      sequences and identified an extensive covariance network. Unexpectedly, amino
      acid covariation was highest between VP4 and VP2, which are structural components
      of the RV virion that are not thought to directly interact. These results suggest
      that GCs may be influenced by the selective constraints placed on functionally
      coadapted, albeit noninteracting, viral proteins. This work raises important
      questions about mutation-reassortment interplay and its impact on human RV
      evolution. IMPORTANCE: Rotaviruses are devastating human pathogens that cause
      severe diarrhea and kill >450,000 children each year. The virus can evolve by
      accumulating mutations and by acquiring new genes from other strains via a
      process called reassortment. However, little is known about the relationship
      between mutation accumulation and gene reassortment for rotaviruses and how it
      impacts viral evolution. In this study, we analyzed the genome sequences of human
      strains found in clinical fecal specimens that were collected at a single
      hospital over an 18-year time span. We found that many rotaviruses did not
      reassort their genes but instead maintained them as specific sets (i.e.,
      constellations). By analyzing the encoded proteins, we discovered concurrent
      amino acid changes among them, which suggests that they are functionally
      coadapted to operate best when kept together. This study increases our
      understanding of how rotaviruses evolve over time in the human population.

PMID- 24942571
TI  - Enterovirus 71 3C inhibits cytokine expression through cleavage of the
      TAK1/TAB1/TAB2/TAB3 complex.
AB  - Enterovirus 71 (EV71) causes hand, foot, and mouth disease in young children and
      infants. Severe infection with EV71 can lead to various neurological
      complications or fatal diseases. However, the mechanism of EV71 pathogenesis is
      poorly understood. Emerging evidence suggests that EV71 modulates type I
      interferon (IFN) and cytokine responses. Here, we show that EV71 disables
      components of the TAB2 complex through the 3C protein. When expressed in
      mammalian cells, EV71 3C interacts with TAB2 and TAK1, which inhibits NF-kappaB
      activation. Furthermore, 3C mediates cleavage of TAB2 and its partners, which
      requires the protease activity. H40D or C147S substitution in the 3C active sites
      abolishes its activity, whereas R84Q or V154S substitution in the RNA binding
      domain has no effect. The 3C protein targets TAB2 at Q113-S114, TAK1 at Q360
      S361, TAB1 both at Q414-G415 and Q451-S452, and TAB3 at Q173-G174 and Q343-G344.
      Importantly, overexpression of TAB2 inhibits EV71 replication, whereas addition
      of cleaved fragments has no effect. Thus, an equilibrium between the TAB2 complex
      and EV71 3C represents a control point of viral infection. These results suggest
      that TAK1/TAB1/TAB2/TAB3 cleavage mediated by EV71 may be a mechanism to
      interfere with inflammatory responses. IMPORTANCE: The TAK1 complex plays a
      critical role in the activation of NF-kappaB and cytokine production. However,
      little is known about its connection to enterovirus 71 (EV71). We demonstrate
      that EV71 3C suppresses cytokine expression via cleavage of the TAK1 complex
      proteins. EV71 3C interacts with TAB2 and TAK1. Furthermore, overexpression of
      TAB2 inhibits EV71 replication, whereas addition of cleaved fragment has no
      effect. These results suggest that the interplay of EV71 and the TAK1 complex
      influences the outcome of viral infection.

PMID- 24942572
TI  - Interaction patterns between potato virus Y and eIF4E-mediated recessive
      resistance in the Solanaceae.
AB  - The structural pattern of infectivity matrices, which contains infection data
      resulting from inoculations of a set of hosts by a set of parasites, is a key
      parameter for our understanding of biological interactions and their evolution.
      This pattern determines the evolution of parasite pathogenicity and host
      resistance, the spatiotemporal distribution of host and parasite genotypes, and
      the efficiency of disease control strategies. Two major patterns have been
      proposed for plant-virus genotype infectivity matrices. In the gene-for-gene
      model, infectivity matrices show a nested pattern, where the host ranges of
      specialist virus genotypes are subsets of the host ranges of less specialized
      viruses. In contrast, in the matching-allele (MA) model, each virus genotype is
      specialized to infect one (or a small set of) host genotype(s). The corresponding
      infectivity matrix shows a modular pattern where infection is frequent for plants
      and viruses belonging to the same module but rare for those belonging to
      different modules. We analyzed the structure of infectivity matrices between
      Potato virus Y (PVY) and plant genotypes in the family Solanaceae carrying
      different eukaryotic initiation factor 4E (eIF4E)-coding alleles conferring
      recessive resistance. Whereas this system corresponds mechanistically to an MA
      model, the expected modular pattern was rejected based on our experimental data.
      This was mostly because PVY mutations involved in adaptation to a particular
      plant genotype displayed frequent pleiotropic effects, conferring simultaneously
      an adaptation to additional plant genotypes with different eIF4E alleles. Such
      effects should be taken into account for the design of strategies of sustainable
      control of PVY through plant varietal mixtures or rotations. IMPORTANCE: The
      interaction pattern between host and virus genotypes has important consequences
      on their respective evolution and on issues regarding the application of disease
      control strategies. We found that the structure of the interaction between Potato
      virus Y (PVY) variants and host plants in the family Solanaceae departs
      significantly from the current model of interaction considered for these
      organisms because of frequent pleiotropic effects of virus mutations. These
      mutational effects allow the virus to expand rapidly its range of host plant
      genotypes, make it very difficult to predict the effects of mutations in PVY
      infectivity factors, and raise concerns about strategies of sustainable
      management of plant genetic resistance to viruses.

PMID- 24942573
TI  - Comparative analysis of the capacity of elite suppressor CD4+ and CD8+ T cells to
      inhibit HIV-1 replication in monocyte-derived macrophages.
AB  - Elite controllers or suppressors (ESs) are HIV-1-infected individuals who are
      able to maintain viral loads below the limit of detection of clinical assays
      without antiretroviral therapy. The mechanisms of virologic control are not fully
      understood, but ESs have been shown to have a more effective CD8+ T cell response
      to infected CD4+ T cells than chronic progressors (CPs). While macrophages are
      another cell type productively infected by HIV-1, few studies have examined the
      ability of primary effector T cells to suppress HIV-1 replication in these target
      cells. Here, we compared the ability of unstimulated primary CD4+ and CD8+
      effector T cells to suppress viral replication in monocyte-derived macrophages
      (MDMs) in ESs and CPs. While CD4+ effector T cells were capable of inhibiting
      viral replication in MDMs, the magnitude of this response was not significantly
      different between ESs and CPs. In contrast, the CD8+ T cells from ESs were
      significantly more effective than those from CPs at inhibiting viral replication
      in MDMs. The CD4+ T cell response was partially mediated by soluble factors,
      while the CD8+ T cell response required cell-to-cell interaction. Our results
      suggest that the individual contributions of various effector cells should be
      considered in rational vaccine design and in ongoing eradication efforts.
      IMPORTANCE: Elite suppressors are individuals capable of maintaining low-level
      viremia in HIV-1 infection without antiretroviral drugs. Their T cell responses
      have been implicated in eliminating infected CD4+ T cells, and as such, elite
      suppressors may represent a model of a functional cure of HIV-1 infection. Here,
      we sought to determine whether the suppressive T cell responses against infected
      CD4+ T cells also apply to infected macrophages by comparing the responses of
      elite suppressors and HIV-1-positive individuals on highly active antiretroviral
      therapy (HAART). Our results show that the CD8+ cells but not CD4+ T cells from
      elite suppressors have a response against infected macrophages superior to the
      response of CD8+ cells from patients on HAART. Our results suggest that the
      induction of a CD8+ T cell response effective against infected macrophages is an
      outcome to consider in rational vaccine design.

PMID- 24942575
TI  - Intercontinental dispersal of HIV-1 subtype B associated with transmission among
      men who have sex with men in Japan.
AB  - Transmission clusters of HIV-1 subtype B uniquely associated with the epidemic
      among men who have sex with men (MSM) in East Asia have recently been identified.
      Using the Los Alamos HIV sequence database and the UK HIV drug resistance
      database, we explored possible links between HIV MSM epidemics in East Asia and
      the rest of the world by using phylogenetic and molecular clock analyses. We
      found that JP.MSM.B-1, a subtype B MSM variant that accounts for approximately
      one-third of the infections among Japanese MSM, was detected worldwide, in the
      United Kingdom (n=13), mainland China (n=3), the United States, Germany, Canada,
      and Taiwan (n=1 each). Interestingly, 10 United Kingdom samples plus two from
      Germany and the United States formed a distinct monophyletic subgroup within
      JP.MSM.B-1. The estimated divergence times of JP.MSM.B-1 and the latter subgroup
      were ~1989 and ~1999, respectively. These dates suggest that JP.MSM.B-1 was
      circulating for many years in Japan among MSM before disseminating to other
      countries, most likely through global MSM networks. A significant number of other
      Asian MSM HIV lineages were also detected in the UK HIV drug resistance database.
      Our study provides insight into the regional and global dispersal of Asian MSM
      HIV lineages. Further study of these strains is warranted to elucidate viral
      migration and the interrelationship of HIV epidemics on a global scale.
      IMPORTANCE: We previously identified several transmission clusters of HIV-1
      subtype B uniquely associated with the epidemic among men who have sex with men
      (MSM) in East Asia. Using the Los Alamos HIV sequence database and the UK HIV
      drug resistance database, we explored the possible interplay of HIV MSM epidemics
      in the different geographic regions and found previously unrecognized
      interrelationships among the HIV-1 epidemics in East Asia, the United Kingdom,
      and the rest of the world. Our study provides insight into the regional and
      global dispersal of Asian MSM HIV lineages and highlights the importance of
      strengthening HIV monitoring efforts and the need for implementing effective
      control measures to reduce HIV transmission on a global scale.

PMID- 24942574
TI  - Uukuniemi Phlebovirus assembly and secretion leave a functional imprint on the
      virion glycome.
AB  - Uukuniemi virus (UUKV) is a model system for investigating the genus Phlebovirus
      of the Bunyaviridae. We report the UUKV glycome, revealing differential
      processing of the Gn and Gc virion glycoproteins. Both glycoproteins display poly
      N-acetyllactosamines, consistent with virion assembly in the medial Golgi
      apparatus, whereas oligomannose-type glycans required for DC-SIGN-dependent
      cellular attachment are predominant on Gc. Local virion structure and the route
      of viral egress from the cell leave a functional imprint on the phleboviral
      glycome. 

PMID- 24942576
TI  - HIV-1 and HIV-2 Vif interact with human APOBEC3 proteins using completely
      different determinants.
AB  - Human APOBEC3 (A3) restriction factors provide intrinsic immunity against
      zoonotic transmission of pathogenic viruses. A3D, A3F, A3G, and A3H haplotype II
      (A3H-hapII) can be packaged into virion infectivity factor (Vif)-deficient HIVs
      to inhibit viral replication. To overcome these restriction factors, Vif binds to
      the A3 proteins in viral producer cells to target them for ubiquitination and
      proteasomal degradation, thus preventing their packaging into assembling virions.
      Therefore, the Vif-A3 interactions are attractive targets for novel drug
      development. HIV-1 and HIV-2 arose via distinct zoonotic transmission events of
      simian immunodeficiency viruses from chimpanzees and sooty mangabeys,
      respectively, and Vifs from these viruses have limited homology. To gain insights
      into the evolution of virus-host interactions that led to successful cross
      species transmission of lentiviruses, we characterized the determinants of the
      interaction between HIV-2 Vif (Vif2) with human A3 proteins and compared them to
      the previously identified HIV-1 Vif (Vif1) interactions with the A3 proteins. We
      found that A3G, A3F, and A3H-hapII, but not A3D, were susceptible to Vif2-induced
      degradation. Alanine-scanning mutational analysis of the first 62 amino acids of
      Vif2 indicated that Vif2 determinants important for degradation of A3G and A3F
      are completely distinct from these regions in Vif1, as are the determinants in
      A3G and A3F that are critical for Vif2-induced degradation. These observations
      suggest that distinct Vif-A3 interactions evolved independently in different SIVs
      and their nonhuman primate hosts and conservation of the A3 determinants targeted
      by the SIV Vif proteins resulted in successful zoonotic transmission into humans.
      IMPORTANCE: Primate APOBEC3 proteins provide innate immunity against invading
      pathogens, and Vif proteins of primate lentiviruses have evolved to overcome
      these host defenses by interacting with them and inducing their proteasomal
      degradation. HIV-1 and HIV-2 are two human pathogens that induce AIDS, and
      elucidating interactions between their Vif proteins and human A3 proteins could
      facilitate the development of novel antiviral drugs. Furthermore, understanding
      Vif-A3 interactions can provide novel insights into the cross-species
      transmission events that led to the HIV-1 and HIV-2 pandemics and evolution of
      host-virus interactions. We carried out mutational analysis of the N-terminal 62
      amino acids of HIV-2 Vif (Vif2) and analyzed A3G/A3F chimeras that retained
      antiviral activity to identify the determinants of the Vif2 and A3 interaction.
      Our results show that the Vif2-A3 interactions are completely different from the
      Vif1-A3 interactions, suggesting that these interactions evolved independently
      and that conservation of the A3 determinants resulted in successful zoonotic
      transmission into humans.

PMID- 24942577
TI  - TALEN knockout of the PSIP1 gene in human cells: analyses of HIV-1 replication
      and allosteric integrase inhibitor mechanism.
AB  - HIV-1 utilizes the cellular protein LEDGF/p75 as a chromosome docking and
      integration cofactor. The LEDGF/p75 gene, PSIP1, is a potential therapeutic
      target because, like CCR5, depletion of LEDGF/p75 is tolerated well by human CD4+
      T cells, and knockout mice have normal immune systems. RNA interference (RNAi)
      has been useful for studying LEDGF/p75, but the potent cofactor activity of small
      protein residua can be confounding. Here, in human cells with utility for HIV
      research (293T and Jurkat), we used transcription activator-like effector
      nucleases (TALENs) to completely eradicate all LEDGF/p75 expression. We performed
      two kinds of PSIP1 knockouts: whole-gene deletion and deletion of the integrase
      binding domain (IBD)-encoding exons. HIV-1 integration was inhibited, and
      spreading viral replication was severely impaired in PSIP1-/- Jurkat cells
      infected at high multiplicity. Furthermore, frameshifting the gene in the first
      coding exon with a single TALEN pair yielded trace LEDGF/p75 levels that were
      virologically active, affirming the cofactor's potency and the value of
      definitive gene or IBD exon segment deletion. Some recent studies have suggested
      that LEDGF/p75 may participate in HIV-1 assembly. However, we determined that
      assembly of infectious viral particles is normal in PSIP1-/- cells. The potency
      of an allosteric integrase inhibitor, ALLINI-2, for rendering produced virions
      noninfectious was also unaffected by total eradication of cellular LEDGF/p75. We
      conclude that HIV-1 particle assembly and the main ALLINI mechanism are LEDGF/p75
      independent. The block to HIV-1 propagation in PSIP1-/- human CD4+ T cells raises
      the possibility of gene targeting PSIP1 combinatorially with CCR5 for HIV-1 cure.
      IMPORTANCE: LEDGF/p75 dependence is universally conserved in the retroviral genus
      Lentivirus. Once inside the nucleus, lentiviral preintegration complexes are
      thought to attach to the chromosome when integrase binds to LEDGF/p75. This
      tethering process is largely responsible for the 2-fold preference for
      integration into active genes, but the cofactor's full role in the lentiviral
      life cycle is not yet clear. Effective knockdowns are difficult because even
      trace residua of this tightly chromatin-bound protein can support integration
      cofactor function. Here, in experimentally useful human cell lines, we used
      TALENs to definitively eradicate LEDGF/p75 by deleting either all of PSIP1 or the
      exons that code for the integrase binding domain. HIV-1 replication was severely
      impaired in these PSIP1 knockout cells. Experiments in these cells also excluded
      a role for LEDGF/p75 in HIV-1 assembly and showed that the main ALLINI mechanism
      is LEDGF/p75 independent. Site-specific gene targeting of PSIP1 may have
      therapeutic potential for HIV-1 disease.

PMID- 24942578
TI  - A novel role of the potyviral helper component proteinase contributes to enhance
      the yield of viral particles.
AB  - The helper component proteinase (HCPro) is an indispensable, multifunctional
      protein of members of the genus Potyvirus and other viruses of the family
      Potyviridae. This viral factor is directly involved in diverse steps of viral
      infection, such as aphid transmission, polyprotein processing, and suppression of
      host antiviral RNA silencing. In this paper, we show that although a chimeric
      virus based on the potyvirus Plum pox virus lacking HCPro, which was replaced by
      a heterologous silencing suppressor, caused an efficient infection in Nicotiana
      benthamiana plants, its viral progeny had very reduced infectivity. Making use of
      different approaches, here, we provide direct evidence of a previously unknown
      function of HCPro in which the viral factor enhances the stability of its cognate
      capsid protein (CP), positively affecting the yield of virions and consequently
      improving the infectivity of the viral progeny. Site-directed mutagenesis
      revealed that the ability of HCPro to stabilize CP and enhance the yield of
      infectious viral particles is not linked to any of its previously known
      activities and helped us to delimit the region of HCPro involved in this function
      in the central region of the protein. Moreover, the function is highly specific
      and cannot be fulfilled by the HCPro of a heterologous potyvirus. The importance
      of this novel requirement in regulating the sorting of the viral genome to be
      subjected to replication, translation, and encapsidation, thus contributing to
      the synchronization of these viral processes, is discussed. IMPORTANCE:
      Potyviruses form one of the most numerous groups of plant viruses and are a major
      cause of crop loss worldwide. It is well known that these pathogens make use of
      virus-derived multitasking proteins, as well as dedicated host factors, to
      successfully infect their hosts. Here, we describe a novel requirement for the
      proper yield and infectivity of potyviral progeny. In this case, such a function
      is performed by the extensively studied viral factor HCPro, which seems to use an
      unknown mechanism that is not linked to its previously described activities. To
      our knowledge, this is the first time that a factor different from capsid protein
      (CP) has been shown to be directly involved in the yield of potyviral particles.
      Based on the data presented here, we hypothesize that this capacity of HCPro
      might be involved in the coordination of mutually exclusive activities of the
      viral genome by controlling correct assembly of CP in stable virions.

PMID- 24942580
TI  - Interactions between E6, FAK, and GIT1 at paxillin LD4 are necessary for
      transformation by bovine papillomavirus 1 E6.
AB  - Bovine papillomavirus 1 E6 interacts with two similar proteins that regulate cell
      attachment and cell migration called paxillin (PXN) and HIC-5 (also known as
      HIC5, ARA55, HIC-5, TSC-5, and TGFB1I1). Despite the similarity between HIC-5 and
      paxillin, paxillin is required for E6 to transform mouse embryo fibroblasts while
      HIC-5 is not. Using mutants of paxillin, we found that dynamic competitive
      interactions between E6, focal adhesion kinase, and the GIT1 ARF-GAP protein for
      binding to paxillin are required but not sufficient for transformation by E6.
      Using mutants of paxillin and chimeric proteins between HIC-5 and paxillin, we
      demonstrate that a critical difference between HIC-5 and paxillin is within the
      LIM domains of paxillin that do not directly interact with E6. Mutational
      analysis indicates that at least six distinct domains of paxillin are required
      for E6 transformation. IMPORTANCE: Papillomaviruses cause epitheliomas in
      vertebrates through the actions of virus-encoded oncoproteins. Despite the
      immense diversity of papillomavirus types, our understanding of the mechanisms by
      which the virus-encoded E6 oncoproteins contribute to cell transformation is
      restricted to human papillomavirus types that are associated with cancer. Bovine
      papillomavirus 1 (BPV-1) E6 has served as a model system for studies of E6
      structure and function. This study examines the mechanisms by which BPV-1 E6
      association with the cellular focal adhesion adapter protein paxillin contributes
      to cell transformation and extends our knowledge of the diverse mechanisms by
      which papillomaviruses transform host cells.

PMID- 24942579
TI  - Regulation of tissue-dependent differences in CD8+ T cell apoptosis during viral
      infection.
AB  - Virus-specific CD8+ T cells in the lymphoid organs contract at the resolution of
      virus infections by apoptosis or by dissemination into peripheral tissues, and
      those residing in nonlymphoid organs, including the peritoneal cavity and fat
      pads, are more resistant to apoptosis than those in the spleen and lymph nodes.
      This stability of memory T cells in the nonlymphoid tissues may enhance
      protection to secondary challenges. Here, we show that lymphocytic
      choriomeningitis virus (LCMV)-specific CD8+ T cells in nonlymphoid tissues were
      enriched for memory precursors (expressing high levels of interleukin-7 receptor
      and low levels of killer cell lectin-like receptor G1 [IL-7Rhi KLRG1lo]) and had
      higher expression of CD27, CXCR3, and T cell factor-1 (TCF-1), each a marker that
      is individually correlated with decreased apoptosis. CD8+ T cells in the
      peritoneal cavity of TCF-1-deficient mice had decreased survival, suggesting a
      role for TCF-1 in promoting survival in the nonlymphoid tissues. CXCR3+ CD8+ T
      cells resisted apoptosis and accumulated in the lymph nodes of mice treated with
      FTY720, which blocks the export of lymph node cells into peripheral tissue. The
      peritoneal exudate cells (PEC) expressed increased amounts of CXCR3 ligands,
      CXCL9 and CXCL10, which may normally recruit these nonapoptotic cells from the
      lymph nodes. In addition, adoptive transfer of splenic CD8+ T cells into PEC or
      spleen environments showed that the peritoneal environment promoted survival of
      CD8+ T cells. Thus, intrinsic stability of T cells which are present in the
      nonlymphoid tissues along with preferential migration of apoptosis-resistant CD8+
      T cells into peripheral sites and the availability of tissue-specific factors
      that enhance memory cell survival may collectively account for the tissue
      dependent apoptotic differences. IMPORTANCE: Most infections are initiated at
      nonlymphoid tissue sites, and the presence of memory T cells in nonlymphoid
      tissues is critical for protective immunity in various viral infection models.
      Virus-specific CD8+ T cells in the nonlymphoid tissues are more resistant to
      apoptosis than those in lymphoid organs during the resolution and memory phase of
      the immune response to acute LCMV infection. Here, we investigated the mechanisms
      promoting stability of T cells in the nonlymphoid tissues. This increased
      resistance to apoptosis of virus-specific CD8+ T cells in nonlymphoid tissues was
      due to several factors. Nonlymphoid tissues were enriched in memory phenotype
      CD8+ T cells, which were intrinsically resistant to apoptosis irrespective of the
      tissue environment. Furthermore, apoptosis-resistant CD8+ T cells preferentially
      migrated into the nonlymphoid tissues, where the availability of tissue-specific
      factors may enhance memory cell survival. Our findings are relevant for the
      generation of long-lasting vaccines providing protection at peripheral infection
      sites.

PMID- 24942582
TI  - Northern African strains of human T-lymphotropic virus type 1 arose from a
      recombination event.
AB  - Although recombination is a major source of genetic variability in retroviruses,
      no recombinant strain had been observed for human T-lymphotropic virus type 1
      (HTLV-1), the first isolated human-pathogenic retrovirus. Different genotypes
      exist for HTLV-1: Genotypes b and d to g are restricted to central Africa, while
      genotype c is only endemic in Australo-Melanesia. In contrast, the cosmopolitan
      genotype a is widely distributed. We applied a combination of phylogenetics and
      recombination analysis approaches to a set of new HTLV-1 sequences, which we
      collected from 19 countries throughout Africa, the continent where the virus has
      the largest endemic presence. This led us to demonstrate the presence of
      recombinants in HTLV-1. Indeed, the HTLV-1 strains currently present in North
      Africa have originated from a recombinant event between strains from Senegal and
      West Africa. This recombination is estimated to have occurred around 4,000 years
      ago. This recombination seems to have been generated during reverse
      transcription. In conclusion, we demonstrate that, albeit rare, recombination can
      occur in HTLV-1 and may play a role in the evolution of this retrovirus.
      IMPORTANCE: A number of HTLV-1 subtypes have been described in different
      populations, but none of the genetic differences between these subtypes have been
      ascribed to recombination events. Here we report an HTLV-1 recombinant virus
      among infected individuals in North Africa. This demonstrates that, contrary to
      what was thought, recombination can occur and could play a role in the evolution
      of HTLV-1.

PMID- 24942581
TI  - CD4 ligation on human blood monocytes triggers macrophage differentiation and
      enhances HIV infection.
AB  - A unique aspect of human monocytes, compared to monocytes from many other
      species, is that they express the CD4 molecule. However, the role of the CD4
      molecule in human monocyte development and function is not known. We determined
      that the activation of CD4 via interaction with major histocompatibility complex
      class II (MHC-II) triggers cytokine expression and the differentiation of human
      monocytes into functional mature macrophages. Importantly, we determined that CD4
      activation induces intracellular signaling in monocytes and that inhibition of
      the MAPK and Src family kinase pathways blocked the ability of CD4 ligation to
      trigger macrophage differentiation. We observed that ligation of CD4 by MHC-II on
      activated endothelial cells induced CD4-mediated macrophage differentiation of
      blood monocytes. Finally, CD4 ligation by MHC-II increases the susceptibility of
      blood-derived monocytes to HIV binding and subsequent infection. Altogether, our
      studies have identified a novel function for the CD4 molecule on peripheral
      monocytes and suggest that a unique set of events that lead to innate immune
      activation differ between humans and mice. Further, these events can have effects
      on HIV infection and persistence in the macrophage compartment. IMPORTANCE: The
      CD4 molecule, as the primary receptor for HIV, plays an important role in HIV
      pathogenesis. There are many cell types that express CD4 other than the primary
      HIV target, the CD4(+) T cell. Other than allowing HIV infection, the role of the
      CD4 molecule on human monocytes or macrophages is not known. We were interested
      in determining the role of CD4 in human monocyte/macrophage development and
      function and the potential effects of this on HIV infection. We identified a role
      for the CD4 molecule in triggering the activation and development of a monocyte
      into a macrophage following its ligation. Activation of the monocyte through the
      CD4 molecule in this manner increases the ability of monocytes to bind to and
      become infected with HIV. Our studies have identified a novel function for the
      CD4 molecule on peripheral monocytes in triggering macrophage development that
      has direct consequences for HIV infection.

PMID- 24942583
TI  - Activation of NF-kappaB via endosomal Toll-like receptor 7 (TLR7) or TLR9
      suppresses murine herpesvirus 68 reactivation.
AB  - In order to understand and possibly treat B-cell malignancies associated with
      latent gammaherpesvirus infection, it is vital to understand the factors that
      control the balance between the two transcriptional states of gammaherpesviruses:
      latency and lytic replication. We used murine gammaherpesvirus 68 (MHV 68) as a
      model system to investigate how engagement of endosomal Toll-like receptors
      (TLRs) impacts reactivation from latency in vitro and establishment of latent
      infection in vivo. We found that treatment with TLR7 ligand R848 or TLR9 ligand
      CpG oligodeoxynucleotide (ODN) suppresses reactivation of MHV 68 in vitro. These
      suppressive effects correlated with the ability to activate cellular
      transcription factor NF-kappaB. Downregulation of TLR9 by RNA interference in
      vitro led to a reduction of nuclear levels of NF-kappaB p65 and consequently to
      an increase of spontaneous reactivation in cells latently infected with MHV 68,
      indicating that the TLR9 pathway suppresses spontaneous reactivation events. In
      vivo, sustained stimulation of TLR7 by repeated R848 treatment led to an
      increased frequency of infected splenocytes compared to mock-treated control
      results. Frequencies of infected splenic B cells in tlr7-/- or tlr9-/- mice after
      establishment of latency did not differ from those seen with their wild-type
      counterparts. Nevertheless, MHV 68-infected B cells from tlr9-/- mice showed a
      higher frequency of reactivation than B cells from wild-type or tlr7-/- mice in
      ex vivo reactivation assays. Thus, we show a suppressive effect of TLR7 or TLR9
      triggering on MHV 68 reactivation that correlates with NF-kappaB activation and
      that the mere presence of a functional TLR9 signaling pathway contributes to
      dampen lytic gammaherpesvirus reactivation in infected cells. IMPORTANCE: A
      hallmark of gammaherpesviruses is their establishment of latency in B cells that
      is reversible through lytic reactivation. Latency can result in B-cell
      malignancies. Activation of the innate immune system is thought to contribute to
      controlling the switch between the transcriptional states of latency and
      reactivation. Nevertheless, the mechanisms involved are not clear. Here, we show
      that engagement of Toll-like receptor 7 (TLR7) and TLR9 suppresses reactivation
      of murine gammaherpesvirus MHV 68 in vitro and that stimulation of TLR7 in vivo
      increases the frequency of infected cells. TLR7 and TLR9 are innate immunity
      sensors of nucleic acids localized in endosomes. Additionally, we demonstrate
      that impairment of TLR9 signaling in latently infected B cells leads to increased
      reactivation. Thus, activated endosomal TLR7 and TLR9 pathways play an important
      role in promoting establishment of latent gammaherpesvirus infection.
      Counteracting signaling of these pathways allows reactivation and could represent
      treatment targets in gammaherpesvirus-associated malignancies.

PMID- 24942584
TI  - The West Nile virus-like flavivirus Koutango is highly virulent in mice due to
      delayed viral clearance and the induction of a poor neutralizing antibody
      response.
AB  - The mosquito-borne West Nile virus (WNV) is responsible for outbreaks of viral
      encephalitis in humans, horses, and birds, with particularly virulent strains
      causing recent outbreaks of disease in eastern Europe, the Middle East, North
      America, and Australia. Previous studies have phylogenetically separated WNV
      strains into two main genetic lineages (I and II) containing virulent strains
      associated with neurological disease. Several WNV-like strains clustering outside
      these lineages have been identified and form an additional five proposed
      lineages. However, little is known about whether these strains have the potential
      to induce disease. In a comparative analysis with the highly virulent lineage I
      American strain (WNVNY99), the low-pathogenicity lineage II strain (B956), a
      benign Australian strain, Kunjin (WNVKUN), the African WNV-like Koutango virus
      (WNVKOU), and a WNV-like isolate from Sarawak, Malaysia (WNVSarawak), were
      assessed for neuroinvasive properties in a murine model and for their replication
      kinetics in vitro. While WNVNY99 replicated to the highest levels in vitro, in
      vivo mouse challenge revealed that WNVKOU was more virulent, with a shorter time
      to onset of neurological disease and higher morbidity. Histological analysis of
      WNVKOU- and WNVNY99-infected brain and spinal cords demonstrated more prominent
      meningoencephalitis and the presence of viral antigen in WNVKOU-infected mice.
      Enhanced virulence of WNVKOU also was associated with poor viral clearance in the
      periphery (sera and spleen), a skewed innate immune response, and poor
      neutralizing antibody development. These data demonstrate, for the first time,
      potent neuroinvasive and neurovirulent properties of a WNV-like virus outside
      lineages I and II. IMPORTANCE: In this study, we characterized the in vitro and
      in vivo properties of previously uncharacterized West Nile virus strains and West
      Nile-like viruses. We identified a West Nile-like virus, Koutango virus (WNVKOU),
      that was more virulent than a known virulent lineage I virus, WNVNY99. The
      enhanced virulence of WNVKOU was associated with poor viral clearance and the
      induction of a poor neutralizing antibody response. These findings provide new
      insights into the pathogenesis of West Nile virus.

PMID- 24942585
TI  - Interactions between the influenza A virus RNA polymerase components and retinoic
      acid-inducible gene I.
AB  - The influenza A virus genome possesses eight negative-strand RNA segments in the
      form of viral ribonucleoprotein particles (vRNPs) in association with the three
      viral RNA polymerase subunits (PB2, PB1, and PA) and the nucleoprotein (NP).
      Through interactions with multiple host factors, the RNP subunits play vital
      roles in replication, host adaptation, interspecies transmission, and
      pathogenicity. In order to gain insight into the potential roles of RNP subunits
      in the modulation of the host's innate immune response, the interactions of each
      RNP subunit with retinoic acid-inducible gene I protein (RIG-I) from mammalian
      and avian species were investigated. Studies using coimmunoprecipitation (co-IP),
      bimolecular fluorescence complementation (BiFc), and colocalization using
      confocal microscopy provided direct evidence for the RNA-independent binding of
      PB2, PB1, and PA with RIG-I from various hosts (human, swine, mouse, and duck).
      In contrast, the binding of NP with RIG-I was found to be RNA dependent.
      Expression of the viral NS1 protein, which interacts with RIG-I, did not
      interfere with the association of RNA polymerase subunits with RIG-I. The
      association of each individual virus polymerase component with RIG-I failed to
      significantly affect the interferon (IFN) induction elicited by RIG-I and 5'
      triphosphate (5'ppp) RNA in reporter assays, quantitative reverse transcription
      PCR (RT-PCR), and IRF3 phosphorylation tests. Taken together, these findings
      indicate that viral RNA polymerase components PB2, PB1, and PA directly target
      RIG-I, but the exact biological significance of these interactions in the
      replication and pathogenicity of influenza A virus needs to be further clarified.
      IMPORTANCE: RIG-I is an important RNA sensor to elicit the innate immune response
      in mammals and some bird species (such as duck) upon influenza A virus infection.
      Although the 5'-triphosphate double-stranded RNA (dsRNA) panhandle structure at
      the end of viral genome RNA is responsible for the binding and subsequent
      activation of RIG-I, this structure is supposedly wrapped by RNA polymerase
      complex (PB2, PB1, and PA), which may interfere with the induction of RIG-I
      signaling pathway. In the present study, PB2, PB1, and PA were found to
      individually interact with RIG-Is from multiple mammalian and avian species in an
      RNA-independent manner, without significantly affecting the generation of IFN.
      The data suggest that although RIG-I binding by RNA polymerase complex is
      conserved in different species, it does not appear to play crucial role in the
      modulation of IFN in vitro.

PMID- 24942587
TI  - Intrinsic innate immunity fails to control herpes simplex virus and vesicular
      stomatitis virus replication in sensory neurons and fibroblasts.
AB  - Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the
      sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity
      to reactivate. The interferon (IFN)-driven antiviral response is critical for the
      control of HSV-1 acute replication. We therefore sought to further investigate
      this response in TG neurons cultured from adult mice deficient in a variety of
      IFN signaling components. Parallel experiments were also performed in fibroblasts
      isolated concurrently. We showed that HSV-1 replication was comparable in wild
      type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a
      similar pattern was observed for the IFN-sensitive vesicular stomatitis virus
      (VSV). Despite these findings, TG neurons responded to IFN-beta pretreatment with
      STAT1 nuclear localization and restricted replication of both VSV and an HSV-1
      strain deficient in gamma34.5, while wild-type HSV-1 replication was unaffected.
      This was in contrast to fibroblasts in which all viruses were restricted by the
      addition of IFN-beta. Taken together, these data show that adult TG neurons can
      mount an effective antiviral response only if provided with an exogenous source
      of IFN-beta, and HSV-1 combats this response through gamma34.5. These results
      further our understanding of the antiviral response of neurons and highlight the
      importance of paracrine IFN-beta signaling in establishing an antiviral state.
      IMPORTANCE: Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that establishes
      a lifelong latent infection in neurons. Reactivation from latency can cause cold
      sores, blindness, and death from encephalitis. Humans with deficiencies in innate
      immunity have significant problems controlling HSV infections. In this study, we
      therefore sought to elucidate the role of neuronal innate immunity in the control
      of viral infection. Using neurons isolated from mice, we found that the intrinsic
      capacity of neurons to restrict virus replication was unaffected by the presence
      or absence of innate immunity. In contrast, neurons were able to mount a robust
      antiviral response when provided with beta interferon, a molecule that strongly
      stimulates innate immunity, and that HSV-1 can combat this response through the
      gamma34.5 viral gene. Our results have important implications for understanding
      how the nervous system defends itself against virus infections.

PMID- 24942586
TI  - Dendritic cells restore CD8+ T cell reactivity to autologous HIV-1.
AB  - Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous
      cellular immune responses generated during infection. Current methods of
      identifying antigen-specific T cell reactivity in HIV-1 infection use bulk
      peripheral blood mononuclear cells (PBMC) yet ignore professional antigen
      presenting cells (APC) that could reveal otherwise hidden responses. In the
      present study, peptides representing autologous variants of major
      histocompatibility complex (MHC) class I-restricted epitopes from HIV-1 Gag and
      Env were used as antigens in gamma interferon (IFN-gamma) enzyme-linked
      immunosorbent spot (ELISpot) and polyfunctional cytokine assays. Here we show
      that dendritic cells (DC) enhanced T cell reactivity at all stages of disease
      progression but specifically restored T cell reactivity after combination
      antiretroviral therapy (cART) to early infection levels. Type 1 cytokine
      secretion was also enhanced by DC and was most apparent late post-cART. We
      additionally show that DC reveal polyfunctional T cell responses after many years
      of treatment, when potential immunotherapies would be implemented. These data
      underscore the potential efficacy of DC immunotherapy that aims to awaken a
      dormant, autologous, HIV-1-specific CD8+ T cell response. IMPORTANCE: Assessment
      of endogenous HIV-1-specific T cell responses is critical for generating
      immunotherapies for subjects on cART. Current assays ignore the ability of
      dendritic cells to reveal these responses and may therefore underestimate the
      breadth and magnitude of T cell reactivity. As DC do not prime new responses in
      these assays, it can be assumed that the observed responses are not detected
      without appropriate stimulation. This is important because dogma states that HIV
      1 mutates to evade host recognition and that CD8+ cytotoxic T lymphocyte (CTL)
      failure is due to the inability of T cells to recognize the autologous virus. The
      results presented here indicate that responses to autologous virus are generated
      during infection but may need additional stimulation to be effective. Detecting
      the breadth and magnitude of HIV-1-specific T cell reactivity generated in vivo
      is of the utmost importance for generating effective DC immunotherapies.

PMID- 24942588
TI  - Murine cytomegalovirus virion-associated protein M45 mediates rapid NF-kappaB
      activation after infection.
AB  - Murine cytomegalovirus (MCMV) rapidly induces activation of nuclear factor kappaB
      (NF-kappaB) upon infection of host cells. After a transient phase of activation,
      the MCMV M45 protein blocks all canonical NF-kappaB-activating pathways by
      inducing the degradation of the gamma subunit of the inhibitor of kappaB kinase
      complex (IKKgamma; commonly referred to as the NF-kappaB essential modulator
      [NEMO]). Here we show that the viral M45 protein also mediates rapid NF-kappaB
      activation immediately after infection. MCMV mutants lacking M45 or expressing C
      terminally truncated M45 proteins induced neither NF-kappaB activation nor
      transcription of NF-kappaB-dependent genes within the first 3 h of infection.
      Rapid NF-kappaB activation was absent in MCMV-infected NEMO-deficient
      fibroblasts, indicating that activation occurs at or upstream of the IKK complex.
      NF-kappaB activation was strongly reduced in murine fibroblasts lacking receptor
      interacting protein 1 (RIP1), a known M45-interacting protein, but was restored
      upon complementation with murine RIP1. However, the ability of M45 to interact
      with RIP1 and NEMO was not sufficient to induce NF-kappaB activation upon
      infection. In addition, incorporation of the M45 protein into virions was
      required. This was dependent on a C-terminal region of M45, which is not required
      for interaction with RIP1 and NEMO. We propose a model in which M45 delivered by
      viral particles activates NF-kappaB, presumably involving an interaction with
      RIP1 and NEMO. Later in infection, expression of M45 induces the degradation of
      NEMO and the shutdown of canonical NF-kappaB activation. IMPORTANCE:
      Transcription factor NF-kappaB is an important regulator of innate and adaptive
      immunity. Its activation can be beneficial or detrimental for viral pathogens.
      Therefore, many viruses interfere with NF-kappaB signaling by stimulating or
      inhibiting the activation of this transcription factor. Cytomegaloviruses,
      opportunistic pathogens that cause lifelong infections in their hosts, activate
      NF-kappaB rapidly and transiently upon infection but block NF-kappaB signaling
      soon thereafter. Here we report the surprising finding that the murine
      cytomegalovirus protein M45, a component of viral particles, plays a dual role in
      NF-kappaB signaling. It not only blocks NF-kappaB signaling later in infection
      but also triggers the rapid activation of NF-kappaB immediately following virus
      entry into host cells. Both activation and inhibition involve M45 interaction
      with the cellular signaling mediators RIP1 and NEMO. Similar dual functions in NF
      kappaB signaling are likely to be found in other viral proteins.

PMID- 24942590
TI  - Triggering TLR2, -3, -4, -5, and -8 reinforces the restrictive nature of M1- and
      M2-polarized macrophages to HIV.
AB  - Macrophages must react to a large number of pathogens and their effects. In
      chronic HIV infection, the microenvironment changes with an influx of microbial
      products that trigger Toll-like receptors (TLRs). That dynamic nature can be
      replicated ex vivo by the proinflammatory (M1-polarized) and alternatively
      activated (M2-polarized) macrophages. Thus, we determined how polarized
      macrophages primed by various TLR agonists support HIV replication. Triggering of
      TLR2, -3, -4, -5, and -8 reinforced the low level of permissiveness in polarized
      macrophages. HIV was inhibited even more in M1-polarized macrophages than in
      macrophages activated only by TLR agonists. HIV was inhibited before its
      integration into the host chromosome. Polarization and triggering by various TLR
      agonists resulted in distinct cytokine profiles, endocytic activity, and distinct
      upregulation of restriction factors of HIV. Thus, different mechanisms likely
      contribute to the HIV-inhibitory effects. In chronic HIV infection, macrophages
      might become less permissive to HIV due to changes in the microenvironment. The
      high level of reactivity of polarized macrophages to TLR triggering may be
      exploited for immunotherapeutic strategies. IMPORTANCE: Macrophages are a major
      target of HIV-1 infection. Different cell types in this very heterogeneous cell
      population respond differently to stimuli. In vitro, the heterogeneity is
      mimicked by their polarization into proinflammatory and alternatively activated
      macrophages. Here we explored the extent to which agonists triggering the TLR
      family affect HIV replication in polarized macrophages. We found that a number of
      TLR agonists blocked HIV replication substantially when given before infection.
      We also report the mechanisms of how TLR agonists exert their inhibitory action.
      Our findings may advance our understanding of which and how TLR agonists block
      HIV infection in polarized macrophages and may facilitate the design of novel
      immunotherapeutic approaches.

PMID- 24942589
TI  - All-in-one bacmids: an efficient reverse genetics strategy for influenza A virus
      vaccines.
AB  - Vaccination is the first line of defense against influenza virus infection, yet
      influenza vaccine production methods are slow, antiquated, and expensive as a
      means to effectively reduce the virus burden during epidemic or pandemic periods.
      There is a great need for alternative influenza vaccines and vaccination methods
      with a global scale of impact. We demonstrate here a strategy to generate
      influenza A virus in vivo by using bacmid DNAs. Compared to the classical reverse
      genetics system, the "eight-in-one" bacmids (bcmd-RGFlu) showed higher efficiency
      of virus rescue in various cell types. Using a transfection-based inoculation
      (TBI) system, intranasal delivery to DBA/2J and BALB/c mice of bcmd-RGFlu plus
      293T cells led to the generation of lethal PR8 virus in vivo. A prime-boost
      intranasal vaccination strategy using TBI in the context of a bcmd-RGFlu carrying
      a temperature-sensitive H1N1 virus resulted in protection of mice against lethal
      challenge with the PR8 strain. Taken together, these studies provide proof of
      principle to highlight the potential of vaccination against influenza virus by
      using in vivo reverse genetics. IMPORTANCE: Vaccination is the first line of
      defense against influenza virus infections. A major drawback in the preparation
      of influenza vaccines is that production relies on a heavily time-consuming
      process of growing the viruses in eggs. We propose a radical change in the way
      influenza vaccination is approached, in which a recombinant bacmid, a shuttle
      vector that can be propagated in both Escherichia coli and insect cells, carries
      an influenza virus infectious clone (bcmd-RGFlu). Using a surrogate cell system,
      we found that intranasal delivery of bcmd-RGFlu resulted in generation of
      influenza virus in mice. Furthermore, mice vaccinated with this system were
      protected against lethal influenza virus challenge. The study serves as a proof
      of principle of a potentially universal vaccine platform against influenza virus
      and other pathogens.

PMID- 24942592
TI  - Randomized trial of autologous bone marrow mesenchymal stem cells transplantation
      for hepatitis B virus cirrhosis: regulation of Treg/Th17 cells.
AB  - BACKGROUND AND AIM: Liver cirrhosis is one of the major consequences of hepatitis
      B virus (HBV) infection, and transplantation of autologous bone marrow
      mesenchymal stem cells (ABMSCs) is one of promising therapies for patients with
      HBV-related liver cirrhosis (HBV-LC). However, the mechanism is unclear. The aim
      of the current study was to explore the role of Treg/Th17 cells in ABMSCs
      transplantation in patients with HBV-LC. METHODS: In this prospective study, 56
      patients were enrolled and randomly assigned to transplantation group and control
      group. After 24-week follow-up, 39 patients completed the study (20 cases in
      transplantation group and 19 cases in control group). The Model for End-Stage
      Liver Disease scores, liver function, changes of Treg/Th17 cells, as well as
      related transcription factors and serum cytokines, were determined. RESULTS:
      Although patients in both groups showed significant improvement after Entecavir
      treatment, ABMSC transplantation further improved patients' liver function.
      Moreover, there was a significant increase in Treg cells and a marked decrease in
      Th17 cells in the transplantation group compared with control, leading to an
      increased Treg/Th17 ratio. Furthermore, mRNA levels of Treg-related transcription
      factor (Foxp3) and Th17-related transcription factor (RORgammat) were increased
      and decreased, respectively. In addition, serum transforming growth factor-beta
      levels were significantly higher at early weeks of transplantation, while serum
      levels of interleukin-17, tumor necrosis factor-alpha, and interleukin-6 were
      significantly lower in patients in the transplantation group compared with
      control. CONCLUSION: ABMSCs transplantation was effective in improving liver
      function in patients with HBV-LC, which was mediated, at least in part, through
      the regulation of Treg/Th17 cell balance.

PMID- 24942591
TI  - Herpes simplex virus type 2 glycoprotein H interacts with integrin alphavbeta3 to
      facilitate viral entry and calcium signaling in human genital tract epithelial
      cells.
AB  - Herpes simplex virus (HSV) entry requires multiple interactions at the cell
      surface and activation of a complex calcium signaling cascade. Previous studies
      demonstrated that integrins participate in this process, but their precise role
      has not been determined. These studies were designed to test the hypothesis that
      integrin alphavbeta3 signaling promotes the release of intracellular calcium
      (Ca2+) stores and contributes to viral entry and cell-to-cell spread.
      Transfection of cells with small interfering RNA (siRNA) targeting integrin
      alphavbeta3, but not other integrin subunits, or treatment with cilengitide, an
      Arg-Gly-Asp (RGD) mimetic, impaired HSV-induced Ca2+ release, viral entry, plaque
      formation, and cell-to-cell spread of HSV-1 and HSV-2 in human cervical and
      primary genital tract epithelial cells. Coimmunoprecipitation studies and
      proximity ligation assays indicated that integrin alphavbeta3 interacts with
      glycoprotein H (gH). An HSV-2 gH-null virus was engineered to further assess the
      role of gH in the virus-induced signaling cascade. The gH-2-null virus bound to
      cells and activated Akt to induce a small Ca2+ response at the plasma membrane,
      but it failed to trigger the release of cytoplasmic Ca2+ stores and was impaired
      for entry and cell-to-cell spread. Silencing of integrin alphavbeta3 and deletion
      of gH prevented phosphorylation of focal adhesion kinase (FAK) and the transport
      of viral capsids to the nuclear pore. Together, these findings demonstrate that
      integrin signaling is activated downstream of virus-induced Akt signaling and
      facilitates viral entry through interactions with gH by activating the release of
      intracellular Ca2+ and FAK phosphorylation. These findings suggest a new target
      for HSV treatment and suppression. IMPORTANCE: Herpes simplex viruses are the
      leading cause of genital disease worldwide, the most common infection associated
      with neonatal encephalitis, and a major cofactor for HIV acquisition and
      transmission. There is no effective vaccine. These epidemiological findings
      underscore the urgency to develop novel HSV treatment or prevention strategies.
      This study addresses this gap by further defining the signaling pathways the
      virus usurps to enter human genital tract epithelial cells. Specifically, the
      study defines the role played by integrins and by the viral envelope glycoprotein
      H in entry and cell-to-cell spread. This knowledge will facilitate the
      identification of new targets for the development of treatment and prevention.

PMID- 24942594
TI  - Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in
      Japanese adult patients with atopic dermatitis: results of a randomized, vehicle
      controlled, multicenter clinical trial.
AB  - The safety and efficacy of topical E6005, a novel phosphodiesterase 4 inhibitor,
      in Japanese adults with atopic dermatitis were evaluated. A total of 78 patients
      were randomized to receive either the 0.2% E6005 ointment or vehicle control
      (without E6005) at an allocation ratio of 2:1. The randomization phase of 4 weeks
      was followed by an extension phase of 8 weeks. In the extension phase, all 67
      subjects who completed the randomization phase were treated with 0.2% E6005
      ointment. The 4-week application of topical E6005 twice daily was safe and well
      tolerated. The safety profile for up to 12 weeks was similar to that for the
      first 4 weeks. No deaths or other serious adverse effects were observed during
      the entire study period of 12 weeks. Plasma E6005 was undetectable in all
      subjects at all sampling points while very low plasma concentrations of an E6005
      metabolite were detected in 47% of subjects receiving E6005 treatment. At the end
      of week 4, Eczema Area and Severity Index (EASI), Severity Scoring Atopic
      Dermatitis (SCORAD)-objective, SCORAD-C (visual analog scales for pruritus and
      sleep loss), itch Behavioral Rating Scale, and the severity of the targeted
      eczematous lesions in the topical E6005 group showed trends toward improvement
      compared with those in the vehicle group (not statistically significant).
      However, the group receiving topical E6005 for 12 weeks showed significant score
      reductions from baselines for EASI (P = 0.030), SCORAD-objective (P < 0.001) and
      SCORAD-C (P = 0.038). These results further support the development of topical
      E6005 for the treatment of atopic dermatitis. 

PMID- 24942593
TI  - Prior doctor shopping resulting from differential treatment correlates with
      differences in current patient-provider relationships.
AB  - OBJECTIVE: To determine the prevalence of doctor shopping resulting from
      differential treatment and to examine associations between this shopping and
      current primary care relationships. METHODS: In 2012, a national internet-based
      survey of 600 adults receiving primary care in the past year with a BMI >= 25
      kg/m(2) was conducted. Our independent variable was "switching doctors because I
      felt treated differently because of my weight." Logistic regression models to
      examine the association of prior doctor shopping with characteristics of current
      primary care relationships: duration, trust in primary care provider (PCP), and
      perceived PCP weight-related judgment, adjusted for patient factors were used.
      RESULTS: Overall, 13% of adults with overweight/obesity reported previously
      doctor shopping resulting from differential treatment. Prior shoppers were more
      likely to report shorter durations of their current relationships [73% vs. 52%; p
      = 0.01] or perceive that their current PCP judged them because of their weight
      [74% vs. 11%; p < 0.01] than nonshoppers. No significant differences in reporting
      high trust in current PCPs were found. CONCLUSIONS: A subset of patients with
      overweight/obesity doctor shop resulting from perceived differential treatment.
      These prior negative experiences have no association with trust in current
      relationships, but our results suggest that patients may remain sensitive to
      provider weight bias.

PMID- 24942596
TI  - Adherence to enhanced recovery after surgery protocols across a high-volume
      gastrointestinal surgical service.
AB  - BACKGROUND AND AIMS: Enhanced recovery after surgery (ERAS) has been shown to
      improve outcomes for patients following gastrointestinal surgery. Data on
      protocol adherence and how this impacts on outcome are limited. This study
      examines how protocol adherence changes over time and determines how this impacts
      on outcome across a large-volume gastrointestinal surgical service. MATERIALS AND
      METHODS: A prospective review of patients eligible for colorectal, liver and
      oesophagogastric ERAS over two 3-month periods in 2010 and 2011 was performed.
      End points included: length of stay (LOS), overall protocol adherence, individual
      modality adherence, reason for pathway deviation and patient outcomes. RESULTS:
      172 patients (110 colorectal, 31 liver and 31 oesophagogastric) were evaluated.
      For each sub-speciality, the introduction of ERAS led to significant reductions
      in LOS that were sustained for the duration of the study. Adherence was achieved
      across 60% (colorectal), 75% (liver) and 88% (oesophagogastric) of individual
      pathway modalities. The major causes of pathway deviation were: post-operative
      nausea and vomiting (colorectal), pain (liver) and pulmonary complications
      (oesophagogastric). CONCLUSIONS: Large-scale implementation of ERAS at a high
      volume centre is feasible and offers many of the benefits demonstrated in
      controlled trials, but adherence may diminish over time.

PMID- 24942595
TI  - Sounds and Charriere: the rest of the story.
AB  - Parisian cutler Joseph-Frederic-Benoit Charriere (1803-1876) contributed greatly
      to surgical disciplines with innovative tools, but his legacy is the gauge system
      he developed in 1842 that is still used for catheters, probes, and dilators.
      Sounding devices have been documented in the surgical armamentarium since 3000
      BC, with practitioners such as Hippocrates, Galen, Celsus, and Al-Zahrawi
      espousing theories on sounding and the related topics of stones and urinary
      obstruction. The medical revolution in 19th-century Paris propelled technology
      and one of the most influential men involved was Charriere, who pioneered diverse
      technical processes in the manufacturing of surgical instruments, led one of the
      largest instrument manufacturing companies, and improved on tools introduced by
      predecessors including his mentor Guillaume Dupuytren. Most importantly he
      created the catheter scale that, despite not being favored in its country of
      origin, became an international standard and is known today as the French system.
      The classification of sounds, catheters, and bougies has undergone many
      variations throughout the years, but the French scale still holds in current
      medical practice as an accurate and nearly universal sizing tool. 

PMID- 24942598
TI  - The importance of being earnest: the role of industry employees in studies about
      their products.

PMID- 24942597
TI  - Emotional content modulates response inhibition and perceptual processing.
AB  - In this study, event-related potentials were used to investigate the effect of
      emotion on response inhibition. Participants performed an emotional go/no-go task
      that required responses to human faces associated with a "go" valence (i.e.,
      emotional, neutral) and response inhibition to human faces associated with a "no
      go" valence. Emotional content impaired response inhibition, as evidenced by
      decreased response accuracy and N2 amplitudes in no-go trials. More importantly,
      emotional expressions elicited larger N170 amplitudes than neutral expressions,
      and this effect was larger in no-go than in go trials, indicating that the
      perceptual processing of emotional expression had priority in inhibitory trials.
      In no-go trials, correlation analysis showed that increased N170 amplitudes were
      associated with decreased N2 amplitudes. Taken together, our findings suggest
      that emotional content impairs response inhibition due to the prioritization of
      emotional content processing. 

PMID- 24942600
TI  - [Interfaces in healthcare].

PMID- 24942601
TI  - [Ambulatory healthcare center in the context of a rheumatology clinic].
AB  - BACKGROUND: The chronic nature of most rheumatic diseases, the complexity of the
      course of the disease and types of therapy used necessitate a close interlocking
      of inpatient and outpatient treatment options. Some years ago in Germany the
      interdisciplinary outpatient and inpatient treatment was facilitated by statutory
      regulations. As the number of rheumatologists in private practice is not
      sufficient to provide adequate rheumatologic outpatient healthcare, the
      improvement of interface points between outpatient and inpatient care becomes
      more important. There are various ways for hospitals to take part in outpatient
      care, one of which is the foundation of an ambulatory healthcare center. METHODS:
      The introduction and integration of a medical healthcare center is described
      using an example. RESULTS: Against the background of insufficient rheumatology
      outpatient care in Cologne a city with 1 million inhabitants, the establishment
      of a rheumatology outpatient healthcare center at Porz am Rhein which is the only
      rheumatology clinic in this region is described.

PMID- 24942603
TI  - [Rituximab: Half dose with full strength?].

PMID- 24942602
TI  - Meta-analysis of genetic polymorphisms in programmed cell death 1. Associations
      with rheumatoid arthritis, ankylosing spondylitis, and type 1 diabetes
      susceptibility.
AB  - OBJECTIVE: The aim of this study was to determine whether genetic polymorphisms
      in programmed cell death 1 (PDCD1 or PD1) are associated with susceptibility to
      rheumatoid arthritis (RA), ankylosing spondylitis (AS), and type 1 diabetes
      (T1D). METHODS: We conducted a meta-analysis to investigate the association
      between PDCD1 polymorphisms and RA, AS, and T1D in the overall population and in
      specific ethnic populations. RESULTS: Sixteen studies, comprising 13,210 patients
      and 17,073 controls, were conducted for the meta-analysis including 4 studies on
      RA, 4 on AS, and 8 on T1D. The meta-analysis showed an association between RA and
      the 2 alleles of the PD1.3 polymorphism in the overall population [odds ratio
      (OR) 1.183, 95 % confidence interval (95 % CI) 1.005-1.392, p = 0.043]. However,
      meta-analysis showed no association between RA and the 2 alleles of the PD1.1 and
      PD1.5 polymorphisms in the overall population. Meta-analysis identified an
      association between AS and the 2 alleles of the PD1.5 and PD1.9 polymorphisms in
      the Asian population (OR 1.251, 95 % CI 1.019-1.535, p = 0.033; OR 1.975, 95 % CI
      1.286-3.034, p = 0.002, respectively). The meta-analysis revealed a significant
      association between T1D and the 2 alleles of the PD1.3 polymorphism in the
      European population (OR 1.098, 95 % CI 1.029-1.171, p = 0.005). The meta-analysis
      showed an association between the PD1.5 polymorphism and T1D in Asians (OR 1.332,
      95 % CI 1.067-1.663, p = 0.011) and between the PD1.9 polymorphism and T1D in the
      Asian population (OR 1.363, 95 % CI 1.107-1.679, p = 0.004). CONCLUSION: The meta
      analysis suggests an association between the PD1.3 polymorphism and RA in the
      overall population and an association between the PD1.5 and PD1.9 polymorphisms,
      and AS in the Asian population. Furthermore, the PD1.3 , 5, and 9 polymorphisms
      were associated with T1D susceptibility in Europeans, or Asians.

PMID- 24942599
TI  - The impact of sleep on soldier performance.
AB  - The military population is particularly vulnerable to a multitude of sleep
      related disorders owing to the type of work performed by active duty
      servicemembers (ADSMs). Inadequate sleep, due to insufficient quantity or
      quality, is increasingly recognized as a public health concern. Traditionally,
      ADSMs have been encouraged that they can adapt to insufficient sleep just as the
      body adapts to physical training, but there is a substantial body of scientific
      literature which argues that this is not possible. Additionally, the military
      work environment creates unique challenges with respect to treatment options for
      common sleep disorders like obstructive sleep apnea, restless legs syndrome, and
      parasomnias. This review highlights sleep disorders which are prevalent in the
      modern military force and discusses the impact of poor sleep on overall
      performance. Medical treatments and recommendations for unit leaders are also
      discussed.

PMID- 24942604
TI  - Relative impact of mate versus pollinator availability on pollen limitation and
      outcrossing rates in a mass-flowering species.
AB  - Plant mating systems are driven by several pre-pollination factors, including
      pollinator availability, mate availability and reproductive traits. We
      investigated the relative contributions of these factors to pollination and to
      realized outcrossing rates in the patchily distributed mass-flowering shrub
      Rhododendron ferrugineum. We jointly monitored pollen limitation (comparing seed
      set from intact and pollen-supplemented flowers), reproductive traits (herkogamy,
      flower size and autofertility) and mating patterns (progeny array analysis) in 28
      natural patches varying in the level of pollinator availability (flower
      visitation rates) and of mate availability (patch floral display estimated as the
      total number of inflorescences per patch). Our results showed that patch floral
      display was the strongest determinant of pollination and of the realized
      outcrossing rates in this mass-flowering species. We found an increase in pollen
      limitation and in outcrossing rates with increasing patch floral display.
      Reproductive traits were not significantly related to patch floral display, while
      autofertility was negatively correlated to outcrossing rates. These findings
      suggest that mate limitation, arising from high flower visitation rates in small
      plant patches, resulted in low pollen limitation and high selfing rates, while
      pollinator limitation, arising from low flower visitation rates in large plant
      patches, resulted in higher pollen limitation and outcrossing rates. Pollinator
      mediated selfing and geitonogamy likely alleviates pollen limitation in the case
      of reduced mate availability, while reduced pollinator availability
      (intraspecific competition for pollinator services) may result in the maintenance
      of high outcrossing rates despite reduced seed production. 

PMID- 24942606
TI  - Development of species-specific quantitative real-time PCR primers for detecting
      anginosus group streptococci based on the rpoB.
AB  - In this study, we introduced species-specific quantitative real-time PCR (qPCR)
      primers designed based on a DNA-dependent RNA polymerase beta-subunit gene for
      detecting anginosus group streptococci (AGS), Streptococcus anginosus, S.
      constellatus, and S. intermedius. The specificity of the qPCR primers was
      confirmed by conventional PCR with the genomic DNAs of 76 strains regarding 44
      bacterial species including the type strain for the target species. The standard
      curves revealed the lower detection limits of these species-specific qPCR primers
      was 40 fg at below a cycle threshold (CT) value of 35. These results suggest that
      AGS species-specific qPCR primers are suitable for applications in
      epidemiological studies associated with infectious diseases related to AGS. 

PMID- 24942605
TI  - Fluvastatin inhibits the expression of fibronectin in human peritoneal
      mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1
      pathway.
AB  - BACKGROUND: Previous studies showed that statins may have protective effects on
      peritoneal mesothelial cells (PMC) cultured in high glucose. However, the
      mechanisms are not clear yet. Several studies demonstrated that serum- and
      glucocorticoid-inducible kinase 1 (SGK1) is implicated in tissue fibrosis of
      liver, lung and kidney by regulating the expression of many profibrogenic
      cytokines and extracellular matrix (e.g., fibronectin). However, few available
      reports elucidated whether the SGK1 is involved in the pathogenesis of peritoneal
      fibrosis (PF) in patients with peritoneal dialysis (PD). So far, there is no
      study about the interaction between the statins and SGK1 in PMC. The purpose of
      this study was to identify whether fluvastatin may decrease the expression of
      fibronectin (FN) in human peritoneal mesothelial cells (HPMC) cultured with high
      glucose peritoneal dialysis solution (HGPDS) by affecting SGK1 signal pathway.
      METHODS: Cultured HPMC were divided into groups of control, high-glucose
      peritoneal dialysis solution (HGPDS), HGPDS with fluvastatin (10(-8) mol/L ~ 10(
      6) mol/L) or GSK650394 10(-5) mol/L (the competitive inhibitor of SGK1),
      fluvastatin 10(-6) mol/L or GSK650394 10(-5) mol/L alone. The expression of SGK1
      and FN was detected by RT-PCR, western immunoblotting or ELISA. RESULTS: Compared
      with the control, the mRNA and protein expression of SGK1 and FN increased
      significantly in HPMC treated with HGPDS (p < 0.05). GSK650394 significantly
      decreased the upregulated mRNA and protein expression of SGK1 and FN induced by
      HGPDS (p < 0.05), and fluvastatin had the same effects as GSK650394 in a dose
      dependent manner (p < 0.05). CONCLUSIONS: Expression of SGK1 and FN increased in
      HPMC induced by HGPDS. Treated with fluvastatin and the SGK1-inhibitor GSK650394,
      abnormalities of SGK1 and FN could be corrected partially, which suggested that
      the SGK1 pathway was implicated in the pathogenesis of PF, and that fluvastatin
      might decrease the expression of SGK1 so as to meliorate the progression of PF.

PMID- 24942609
TI  - Quantifying myocardial inflammation using F18-fluorodeoxyglucose positron
      emission tomography in cardiac sarcoidosis.

PMID- 24942610
TI  - Relationship of decreased accumulation of (99m)Tc-tetrofosmin on myocardial
      single-photon emission computed tomography images between QRS duration in dilated
      cardiomyopathy patient with left bundle branch block.
AB  - PURPOSE: This study aimed to clarify the relationship between severity of
      conduction delay in the left ventricle and myocardial uptake of (99m)Tc
      tetrofosmin (TF) in dilated cardiomyopathy (DCM) patients with left bundle branch
      block (LBBB). METHODS AND RESULTS: Thirty-two DCM patients with LBBB underwent
      electrocardiography and (99m)Tc-TF myocardial single-photon emission computed
      tomography (SPECT). SPECT images were acquired at 30 min (early images) and 3 h
      (late images) after injection. We calculated the total defect score (TDS) using a
      20-segment model with a 5-point scoring system. The TDS in early and late images
      was defined as the summed early score (SES) and summed late score (SLS),
      respectively. On early images, 29 of 32 patients (91%) had decreased tracer
      uptake in the septum. All patients showed a decreased tracer uptake in the septum
      on late images. A significant correlation was observed between TDS (both SES and
      SLS) and QRS duration, with SLS showing an excellent correlation (SES: r = 0.554,
      P < 0.001; SLS: r = 0.779, P < 0.0001). CONCLUSIONS: These findings suggest that
      in DCM patients with LBBB, hypoperfusion and myocardial damage in the septum
      might occur in accordance with an increase in the QRS duration.

PMID- 24942608
TI  - Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-to
      mediastinum ratios to overcome camera-collimator variations.
AB  - BACKGROUND: The heart-to-mediastinum ratio (HMR) of (123)I
      metaiodobenzylguanidine (MIBG) showed variations among institutions and needs to
      be standardized among various scinticamera-collimator combinations. METHODS: A
      total of 225 phantom experiments were performed in 84 institutions to calculate
      cross-calibration coefficients of HMR. Based on phantom studies, a conversion
      coefficient for each camera-collimator system was created, including low-energy
      (LE, n = 125) and a medium-energy (ME, n = 100) collimators. An average
      conversion coefficient from the most common ME group was used to calculate the
      standard HMR. In clinical MIBG studies (n = 52) from three institutions, HMRs
      were standardized from both LE- and ME-type collimators and classified into risk
      groups of <1.60, 1.60-2.19, and >=2.20. RESULTS: The average conversion
      coefficients from the individual camera-collimator condition to the
      mathematically calculated reference HMR ranged from 0.55 to 0.75 for LE groups
      and from 0.83 to 0.95 for ME groups. The conversion coefficient of 0.88 was used
      to unify HMRs from all acquisition conditions. Using the standardized HMR,
      clinical studies (n = 52) showed good agreement between LE and ME types regarding
      three risk groups (kappa = 0.83, P < .0001, complete agreement in 90%, 42% of the
      patients reclassified into the same risk group). CONCLUSION: By using the
      reference HMR and conversion coefficients for the system, HMRs with various
      conditions can be converted to the standard HMRs in a range of normal to low
      HMRs.

PMID- 24942611
TI  - Stress positron emission tomography is safe and can guide coronary
      revascularization in high-risk patients being considered for transcatheter aortic
      valve replacement.
AB  - BACKGROUND: The safety and accuracy of regadenoson stress positron emission
      tomography (PET) in patients with significant aortic stenosis (AS) is unknown. In
      patients undergoing surgical aortic valve replacement, coronary artery bypass
      grafting for coronary artery disease is standard, but the appropriate
      revascularization strategy in patients undergoing TAVR is uncertain. Stress PET
      may identify patients that benefit from revascularization. METHODS: Fifty
      consecutive patients who were referred for consideration of TAVR and underwent a
      stress PET study were retrospectively identified. We assessed major adverse
      cardiac events and significant decreases in systolic blood pressure. The
      percentage of jeopardized myocardium was determined by combining ischemic and
      hibernating myocardium. RESULTS: Our patients were high risk with a mean Society
      of Thoracic Surgeons mortality score of 11.4% and had severe AS with a moderately
      reduced left ventricular ejection fraction (EF) (mean aortic valve area of 0.78
      +/- 0.25 cm(2) and mean EF of 39 +/- 16%). There were no major adverse events
      during testing. Transient hypotension occurred in 16% of the patients.
      Revascularization was performed in 44% of patients, and 91% of these patients had
      revascularization to territories jeopardized on PET. These patients had
      substantial jeopardized myocardium (median 19%), and only 3 patients underwent
      revascularization despite less than 10% jeopardized myocardium. CONCLUSIONS:
      Stress cardiac PET with regadenoson can be performed safely in patients with
      severe AS. Results of the PET study can accurately direct subsequent
      revascularization.

PMID- 24942613
TI  - The Goals of Patient Care project: implementing a proactive approach to patient
      centred decision-making.
AB  - BACKGROUND: Patients in the later stages of their lives risk being harmed by
      futile or unwanted interventions if realistic care goals and patient values are
      not recognised. Doctors have difficulty discussing and informing patients'
      healthcare goals. AIMS: To review implementation of a Goals of Patient Care
      (GOPC) summary in medical inpatients and its applicability in emergency medical
      response (EMR) situations. METHODS: Single-centre cross-sectional study of adult
      medical inpatients and adult inpatients requiring EMR at a Victorian general
      hospital. MEASURES: presence and content of GOPC summary, secondary review of
      decision-making and discussion documentation, patient characteristics; EMR
      precipitants and outcomes. RESULTS: GOPC were documented for 82 of 101 patients.
      One had an existing advance directive, and six had records of a patient-appointed
      substitute decision-maker. For patients with GOPC, 80 had life-prolonging
      treatment aims, with a varying degree of treatment limitation in 48. Discussion
      with patient or substitute decision-maker was evident in 43 cases. GOPC were
      documented prior to nine of 23 EMR. The EMR triggered a GOPC modification in
      three instances. CONCLUSIONS: Introduction of a routine GOPC summary encourages
      consideration of goals of care for most medical inpatients. Few have pre-existing
      records of their wishes, and there are opportunities for improvement in this
      regard. Doctors may still have difficulty determining goals of care, and
      discussion of GOPC with patients and families may not be clearly documented. Most
      patients requiring EMR do not have prior GOPC review, and the role of the summary
      in these situations remains unclear.

PMID- 24942612
TI  - Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and
      mediates inflammation-induced hypersensitivity.
AB  - BACKGROUND: Mounting evidence points to individual contributions of tumour
      necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the
      induction and maintenance of various pain states. Here we explore the role of
      spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF
      and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal
      JNK activity in vivo. METHODS: TNF levels in lumbar cerebrospinal fluid (CSF)
      were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by
      real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun
      phosphorylation by western blotting. The role of spinal TNF and JNK in
      inflammation-induced mechanical and thermal hypersensitivity was assessed by
      injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1
      intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by
      assessing the effect of i.t. etanercept on inflammation-induced spinal JNK
      activity. RESULTS: TNF levels were increased in CSF and spinal cord following
      carrageenan-induced inflammation. While JNK phosphorylation followed the same
      temporal pattern as TNF, c-jun was only activated at later time points.
      Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced
      mechanical and thermal hypersensitivity. TNF stimulation induced JNK
      phosphorylation in cultured spinal astrocytes and blocking the spinal actions of
      TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal
      JNK activity. CONCLUSIONS: Here we show that spinal JNK activity is dependent on
      TNF and that both TNF and the JNK signalling pathways modulate pain-like
      behaviour induced by peripheral inflammation.

PMID- 24942614
TI  - Prefabricated composite resin veneers--a clinical review.
AB  - OBJECTIVE: This clinical technique article is focused on the use of prefabricated
      veneers to enhance the esthetic appearance of the anterior dentition in patients
      who needed an alternative esthetic solution more affordable than traditional
      porcelain veneers. CLINICAL CONSIDERATIONS: Because prefabricated composite
      veneer systems have been recently introduced, they are not widely used. The
      Componeer system (Coltene, Altstatten, Switzerland) contains thin pre-polymerized
      hybrid composite shells, several shades of a direct hybrid composite resin, an
      etch-and-rinse adhesive system, and restorative accessories including finishing
      points and disks. The prefabricated restorations can be customized in the mouth
      for color and shape. The technique described in this article can be used to
      restore function and esthetics in one office visit. CONCLUSIONS: The
      prefabricated composite veneer technique has some of the advantages of direct
      composite restorations, as only one session is required without the need to take
      impressions to send to the dental laboratory. This new treatment option may open
      new opportunities for dental professionals and their patients. However, it is
      paramount to carry out controlled clinical studies with this restorative
      technique prior to recommending it without restrictions in general practice.
      CLINICAL SIGNIFICANCE: The clinical technique described in this paper has the
      potential for being used routinely to lengthen anterior teeth, to correct
      malpositioned teeth, to mask discolorations, and to close diastemas. The
      technique can also be used to restore extensive caries lesions and tooth
      fractures, and to refurbish large old anterior restorations, especially when
      other treatment options are out of reach for the patient for financial reasons.

PMID- 24942615
TI  - Efficacy of Melissa officinalis in suppressing ventricular arrhythmias following
      ischemia-reperfusion of the heart: a comparison with amiodarone.
AB  - OBJECTIVE: We aimed to assess the influence of Melissa officinalis (lemon balm),
      a well-known herbal drug with numerous applications in traditional and modern
      medicine, on cardiac conduction and susceptibility to lethal ventricular
      arrhythmia. MATERIALS AND METHODS: Forty-two male Wistar rats were divided into a
      control group (CTL), an M. officinalis group that received the aqueous extract of
      M. officinalis L. intraperitoneally (i.p.) at dosages of 50, 100, 200 and 400
      mg/ml/kg, respectively, and an amiodarone group (Amio group) that received 30
      mg/ml/kg i.p. of amiodarone. Heart ischemia/reperfusion was induced by the
      ligation and release of the left anterior descending branch of the left coronary
      artery. RESULTS: There were no statistical differences between the groups in the
      basal heart rate and blood pressure. PR, corrected QT (QTc) and QRS intervals
      increased in the M. officinalis and Amio groups. PR and QTc were statistically
      significant only in the Amio group and QRS was significant only in the group
      receiving 400 mg of M. officinalis (M400 group) in comparison with the CTL group.
      During the reperfusion period, the decrease in ventricular fibrillations was
      statistically significant in all groups (except the M400 group) when compared
      with the CTL group. The score of arrhythmia severity also decreased, but was
      statistically significant only in the Amio group (p < 0.05 vs. CTL group).
      CONCLUSIONS: Our findings suggest that M. officinalis extract has a mild
      protective effect against reperfusion-induced lethal ventricular arrhythmias in
      rats.

PMID- 24942616
TI  - Difference in postural control between patients with functional and mechanical
      ankle instability.
AB  - BACKGROUND: Lateral ankle sprain is one of the most common injuries. Since the
      structural and pathological differences in mechanical ankle instability (MAI) and
      functional ankle instability (FAI) may not be the same, it may be better to treat
      these as separate groups. The purpose of this study was to compare the difference
      in postural sway between MAI and FAI in patients with chronic ankle instability
      (CAI). METHODS: Twenty-six patients with CAI and 14 healthy control participants
      were included in the study. The CAI patients were subdivided into MAI (15
      patients) and FAI (11 patients) groups. Patients who were diagnosed with lateral
      ankle ligaments rupture by magnetic resonance imaging and ultrasonography were
      assigned to the MAI group. All participants performed single-limb postural sway
      tests 3 times on each leg with eyes closed and open. The average distances from
      the mean center of pressure position in the mediolateral and anteroposterior
      directions were recorded and compared among the 3 groups. RESULTS: The unstable
      ankles in the MAI group showed significantly greater postural sway in the
      anterior, posterior, and medial directions compared with those in the control
      group with eyes closed. With eyes open, significantly greater postural sway was
      found in the anterior direction. In the FAI group, no difference was found in
      postural sway compared with those in the control group. The MAI group showed
      significantly greater postural sway in the anterior direction compared with the
      FAI group with eyes closed and open. No significant difference in postural sway
      was found between the unstable and stable ankles in the MAI or FAI groups, with
      or without vision. CONCLUSIONS: Patients with MAI have deficits in postural
      control, especially in anterior-posterior directions. However, no difference was
      found in postural sway in patients with FAI compared with healthy people.
      CLINICAL RELEVANCE: As MAI patients suffer from deficits in postural control,
      balance training should be applied in those patients. In addition, special
      training should also include the contralateral side after a unilateral ankle
      ligament injured.

PMID- 24942617
TI  - The influence of concomitant triceps surae lengthening at the time of total ankle
      arthroplasty on postoperative outcomes.
AB  - BACKGROUND: Concomitant procedures are being performed with total ankle
      replacement (TAR) to improve alignment, function, and mobility. The purpose of
      this study was to examine the differences in outcomes between patients who had a
      concomitant triceps surae lengthening (gastrocnemius recession [GSR] or triple
      hemisection [TAL]) versus a group that underwent TAR alone preoperatively and 1
      year after TAR. METHODS: For this prospective, nonrandomized study, 229 patients
      (37 GSR, 22 TAL, and 170 TAR alone) were examined. Patient-reported outcomes,
      physical performance, and lower extremity gait mechanics were completed
      preoperatively and 1 year postoperatively. A series of repeated measures ANOVAs
      were used to determine significant differences (P < .05), and Tukey's post hoc
      testing was used to follow any significant ANOVA results. RESULTS: No difference
      existed in BMI, age, gender, or dorsiflexion (DF) angle at heel strike between
      the triceps surae lengthening groups or between preoperative and 1 year following
      TAR. Walking speed, the physical performance measures, the AOFAS Hindfoot Score,
      SF-36, peak plantar flexion angle, and the peak plantar flexion moment were
      significantly improved (P < .001) postoperatively with no differences between the
      triceps surae lengthening groups. The peak DF angle (P = .006) and the ankle
      range of motion (P = .014) demonstrated a greater improvement from preoperative
      to 1 year postoperatively in the triceps surae lengthening groups in comparison
      to the TAR alone group. CONCLUSION: Significant improvements existed between
      preoperative and 1 year postoperatively for most of the variables of interest
      independent of the triceps surae lengthening group. This study demonstrated that
      the use of a concomitant triceps surae lengthening procedure (GSR or TAL)
      resulted in equivalent outcomes when compared with a group undergoing TAR alone.
      LEVEL OF EVIDENCE: Level II, prospective comparative study.

PMID- 24942618
TI  - Evaluation of posterior malleolar fractures and the posterior pilon variant in
      operatively treated ankle fractures.
AB  - BACKGROUND: Substantial attention has recently been placed on fractures of the
      posterior malleolus. Fracture extension to the posteromedial rim ("posterior
      pilon variant") may result in articular incongruity and talar subluxation.
      Current classification systems fail to account for these fractures. The relative
      frequency of this fracture, its associated patient characteristics, and the
      reliability of its diagnosis have never been reported in such a large series.
      METHODS: We retrospectively identified 270 patients who met our inclusion
      criteria. Basic demographic data were collected. The fractures were classified
      according to Lauge-Hansen and AO/OTA. Additional radiographic data included
      whether the fracture involved the posterior malleolus and whether the fracture
      represented a posterior pilon variant. Univariate statistical methods, chi-square
      analysis, and interobserver reliability were assessed. RESULTS: The relative
      frequency of posterior malleolus fracture was 50%. The relative frequency of the
      posterior pilon variant was 20%. No significant difference was noted with respect
      to the frequency of posterior malleolar or posterior pilon variant between the
      subgroups of the AO/OTA and Lauge-Hansen classification systems when compared to
      the overall fracture distribution. Patients with posterior malleolar fractures
      and posterior pilon variants were significantly older. Females were significantly
      more likely than men to sustain posterior malleolar fractures and posterior pilon
      variants. Patients with diabetes trended toward a greater risk of both types of
      fractures. Interobserver reliability data revealed substantial agreement for
      posterior malleolar fractures and posterior pilon variants. CONCLUSION: These
      data represent the highest reported rate of posterior malleolar involvement in
      operatively treated ankle fractures and is the first to describe the percentage
      of the posterior pilon variant in such a large series. The interobserver
      reliability data demonstrate substantial agreement in identification of posterior
      malleolar fractures and the posterior pilon variant based on plain radiographs.
      Certain patient characteristics such as age, sex, and diabetes may be associated
      with these fractures. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

PMID- 24942619
TI  - Admission chest radiographs predict illness severity for children hospitalized
      with pneumonia.
AB  - OBJECTIVE: To assess whether radiographic findings predict outcomes among
      children hospitalized with pneumonia. METHODS: This retrospective study included
      children <18 years of age from 4 children's hospitals admitted in 2010 with
      clinical and radiographic evidence of pneumonia. Admission radiographs were
      categorized as single lobar, unilateral or bilateral multilobar, or interstitial.
      Pleural effusions were classified as absent, small, or moderate/large. Propensity
      scoring was used to adjust for potential confounders, including need for
      supplemental oxygen, intensive care, and mechanical ventilation, as well as
      hospital length of stay and duration of supplemental oxygen. RESULTS: There were
      406 children (median age, 3 years). Infiltrate patterns included: single lobar,
      61%; multilobar unilateral, 13%; multilobar bilateral, 16%; and interstitial,
      10%. Pleural effusion was present in 21%. Overall, 63% required supplemental
      oxygen (median duration, 31.5 hours), 8% required intensive care, and 3% required
      mechanical ventilation. Median length of stay was 51.5 hours. Compared with
      single lobar infiltrate, all other infiltrate patterns were associated with need
      for intensive care; only bilateral multilobar infiltrate was associated with need
      for mechanical ventilation (adjusted odds ratio [aOR]: 3.0, 95% confidence
      interval [CI]: 1.2-7.9). Presence of effusion was associated with increased
      length of stay and duration of supplemental oxygen; only moderate/large effusion
      was associated with need for intensive care (aOR: 3.2, 95% CI: 1.1-8.9) and
      mechanical ventilation (aOR: 14.8, 95% CI: 9.8-22.4). CONCLUSIONS: Admission
      radiographic findings are associated with important hospital outcomes and care
      processes and may help predict disease severity.

PMID- 24942620
TI  - More than meets the eye: a rapidly progressive skin infection in a football
      player.
AB  - Fournier gangrene (FG) is a rare polymicrobial infection of perineum that carries
      a high mortality rate. Survival depends on rapid identification of the infection
      with early and extensive debridement of necrotic tissue. We present a case of an
      otherwise healthy American football offensive lineman who was initially
      hospitalized for gluteal abscess and advancing cellulitis. The patient was
      discovered to have FG during intraoperative debridement of the abscess and was
      subsequently treated with several weeks of broad-spectrum antibiotics. This case
      highlights the importance that team physicians play in the identification and
      appropriate management of potentially life-threatening infections. 

PMID- 24942621
TI  - Use of supplements by Japanese elite athletes for the 2012 Olympic Games in
      London.
AB  - OBJECTIVE: To investigate supplement use among Japanese elite athletes. DESIGN:
      We conducted a cross-sectional survey study using individual interviews during
      athletes' medical evaluations. SETTING: One to 5 months before the Olympic Games
      in 2012, London, United Kingdom. PARTICIPANTS: Five hundred fifty-two Japanese
      athletes for the London Games, including candidates. INDEPENDENT VARIABLES: Sex,
      sports, supplement category, and participation. MAIN OUTCOME MEASURES: Whether
      athletes used supplements, what products were used, the frequency and purposes of
      use, and from what sources athletes received information on supplements. RESULTS:
      All 552 athletes were interviewed by pharmacists regarding supplement use and
      agreed to the survey. Of them, 452 (81.9%) used 1 or more supplement products in
      the year before the study; a total of 952 different products (mean = 1.7, SD =
      1.4) were used. The most commonly used supplement was amino acids (310 athletes;
      56.2%), and 358 (38.7%) of the total products were amino acids. Of the athletes,
      241 (43.7%) took at least 1 supplement daily, and of the supplements, 457 (49.4%)
      were taken daily. The most common purpose for supplement use was recovery from
      fatigue-327 (59.2%) athletes chose this answer, and 486 (52.5%) products were
      used for this purpose. Finally, regarding athletes' information sources on
      supplements, coaches, managers, and trainers were the most frequent advisors (275
      athletes, 49.8%; 466 products, 50.4%). CONCLUSIONS: The results revealed
      widespread supplement use among Japanese elite athletes for the London Olympic
      Games. Education system was required not only for athletes but also for athletes'
      entourage, such as coaches, managers, trainers, and supplement companies.
      CLINICAL RELEVANCE: This study will provide basic data for establishing an
      education system that would better guide athletes' use of supplements.

PMID- 24942622
TI  - Greater trochanter apophysitis in the adolescent athlete.
AB  - Lower limb traction apophysitis is common in young athletes, occurring at sites
      such as the tibial tubercle (Osgood-Schlatter disease) and distal patella
      (Sinding-Larsen-Johansson disease). Around the hip, iliac apophysitis is well
      recognized, but no cases of greater trochanter apophysitis have previously been
      reported. We describe the case of a 15-year-old male basketball player with a 2
      month history of the right hip pain and significant functional limitation. X-rays
      revealed widening of the greater trochanter apophysis with subchondral sclerosis,
      consistent with a diagnosis of traction apophysitis. The patient was treated with
      a period of relative rest and anti-inflammatory medication. He gradually returned
      to full athletic activity, including basketball, without recurrence of pain or
      limitation. We describe the first reported case of traction apophysitis of the
      greater trochanter. The unique muscular anatomy of this apophysis with balanced
      forces explains the rarity of this condition. If encountered, rest and activity
      modification is the recommended treatment. 

PMID- 24942623
TI  - The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and
      accelerates deadenylation.
AB  - PUF proteins are potent repressors that serve important roles in stem cell
      maintenance, neurological processes, and embryonic development. These functions
      are driven by PUF protein recognition of specific binding sites within the 3'
      untranslated regions of target mRNAs. In this study, we investigated mechanisms
      of repression by the founding PUF, Drosophila Pumilio, and its human orthologs.
      Here, we evaluated a previously proposed model wherein the Pumilio RNA binding
      domain (RBD) binds Argonaute, which in turn blocks the translational activity of
      the eukaryotic elongation factor 1A. Surprisingly, we found that Argonautes are
      not necessary for repression elicited by Drosophila and human PUFs in vivo. A
      second model proposed that the RBD of Pumilio represses by recruiting
      deadenylases to shorten the mRNA's polyadenosine tail. Indeed, the RBD binds to
      the Pop2 deadenylase and accelerates deadenylation; however, this activity is not
      crucial for regulation. Rather, we determined that the poly(A) is necessary for
      repression by the RBD. Our results reveal that poly(A)-dependent repression by
      the RBD requires the poly(A) binding protein, pAbp. Furthermore, we show that
      repression by the human PUM2 RBD requires the pAbp ortholog, PABPC1. Pumilio
      associates with pAbp but does not disrupt binding of pAbp to the mRNA. Taken
      together, our data support a model wherein the Pumilio RBD antagonizes the
      ability of pAbp to promote translation. Thus, the conserved function of the PUF
      RBD is to bind specific mRNAs, antagonize pAbp function, and promote
      deadenylation. 

PMID- 24942626
TI  - Characterizing the ex vivo mechanical properties of synthetic polypropylene
      surgical mesh.
AB  - The use of synthetic polypropylene mesh for hernia surgical repair and the
      correction of female pelvic organ prolapse have been controversial due to
      increasing post-operative complications, including mesh erosion, chronic pain,
      infection and support failure. These morbidities may be related to a mismatch of
      mechanical properties between soft tissues and the mesh. The aim of this study
      was to gain a better understanding of the biomechanical behavior of Prolene
      polypropylene mesh (Ethicon, Sommerville, NJ, USA), which is widely used for a
      variety of surgical repair procedures. The stiffness and permanent deformation of
      Prolene mesh were compared in different directions by performing uniaxial tensile
      failure tests, cyclic and creep tests at simulated physiological loads in the
      coursewise (0 degrees ), walewise (90 degrees ) and the diagonal (45 degrees )
      directions. Failure tests suggest that the mechanical properties of the mesh is
      anisotropic; with response at 0 degrees  being the most compliant while 90
      degrees  was the stiffest. Irreversible deformation and viscoelastic behavior
      were observed in both cyclic and creep tests. The anisotropic property may be
      relevant to the placement of mesh in surgery to maximize long term mesh
      performance. The considerable permanent deformation may be associated with an
      increased risk of post-operative support failure. 

PMID- 24942627
TI  - Numerical optimization of open-porous bone scaffold structures to match the
      elastic properties of human cortical bone.
AB  - Treatment of large segmental bone defects, especially in load bearing areas, is a
      complex procedure in orthopedic surgery. The usage of additive manufacturing
      processes enables the creation of customized bone implants with arbitrary open
      porous structure satisfying both the mechanical and the biological requirements
      for a sufficient bone ingrowth. Aim of the present numerical study was to
      optimize the geometrical parameters of open-porous titanium scaffolds to match
      the elastic properties of human cortical bone with respect to an adequate pore
      size. Three different scaffold designs (cubic, diagonal and pyramidal) were
      numerically investigated by using an optimization approach. Beam elements were
      used to create the lattice structures of the scaffolds. The design parameters
      strut diameter and pore size ranged from 0.2 to 1.5mm and from 0 to 3.0mm,
      respectively. In a first optimization step, the geometrical parameters were
      varied under uniaxial compression to obtain a structural modulus of 15GPa
      (Young's modulus of cortical bone) and a pore size of 800um was aimed to enable
      cell ingrowth. Furthermore, the mechanical behavior of the optimized structures
      under bending and torsion was investigated. Results for bending modulus were
      between 9.0 and 14.5GPa. In contrast, shear modulus was lowest for cubic and
      pyramidal design of approximately 1GPa. Here, the diagonal design revealed a
      modulus of nearly 20GPa. In a second step, large-sized bone scaffolds were
      created and placed in a biomechanical loading situation within a 30mm segmental
      femoral defect, stabilized with an osteosynthesis plate and loaded with
      physiological muscle forces. Strut diameter for the 17 sections of each scaffold
      was optimized independently in order to match the biomechanical stability of
      intact bone. For each design, highest strut diameter was found at the
      dorsal/medial site of the defect and smallest strut diameter in the center. In
      conclusion, we demonstrated the possibility of providing optimized open-porous
      scaffolds for bone regeneration by considering both mechanical and biological
      aspects. Furthermore, the results revealed the need of the investigation and
      comparison of different load scenarios (compression, bending and torsion) as well
      as complex biomechanical loading for a profound characterization of different
      scaffold designs. The usage of a numerical optimization process was proven to be
      a feasible tool to reduce the amount of the required titanium material without
      influencing the biomechanical performance of the scaffold negatively. By using
      fully parameterized models, the optimization approach is adaptable to other
      scaffold designs and bone defect situations. 

PMID- 24942624
TI  - Adaptive evolution of testis-specific, recently evolved, clustered miRNAs in
      Drosophila.
AB  - The propensity of animal miRNAs to regulate targets bearing modest
      complementarity, most notably via pairing with miRNA positions ~2-8 (the "seed"),
      is believed to drive major aspects of miRNA evolution. First, minimal targeting
      requirements have allowed most conserved miRNAs to acquire large target cohorts,
      thus imposing strong selection on miRNAs to maintain their seed sequences.
      Second, the modest pairing needed for repression suggests that evolutionarily
      nascent miRNAs may generally induce net detrimental, rather than beneficial,
      regulatory effects. Hence, levels and activities of newly emerged miRNAs are
      expected to be limited to preserve the status quo of gene expression. In this
      study, we unexpectedly show that Drosophila testes specifically express a
      substantial miRNA population that contravenes these tenets. We find that multiple
      genomic clusters of testis-restricted miRNAs harbor recently evolved miRNAs,
      whose experimentally verified orthologs exhibit divergent sequences, even within
      seed regions. Moreover, this class of miRNAs exhibits higher expression and
      greater phenotypic capacities in transgenic misexpression assays than do non
      testis-restricted miRNAs of similar evolutionary age. These observations suggest
      that these testis-restricted miRNAs may be evolving adaptively, and several
      methods of evolutionary analysis provide strong support for this notion.
      Consistent with this, proof-of-principle tests show that orthologous miRNAs with
      divergent seeds can distinguish target sensors in a species-cognate manner.
      Finally, we observe that testis-restricted miRNA clusters exhibit extraordinary
      dynamics of miRNA gene flux in other Drosophila species. Altogether, our findings
      reveal a surprising tissue-directed influence of miRNA evolution, involving a
      distinct mode of miRNA function connected to adaptive gene regulation in the
      testis. 

PMID- 24942625
TI  - A Spinach molecular beacon triggered by strand displacement.
AB  - We have re-engineered the fluorescent RNA aptamer Spinach to be activated in a
      sequence-dependent manner. The original Spinach aptamer was extended at its 5'-
      and 3'-ends to create Spinach.ST, which is predicted to fold into an inactive
      conformation and thus prevent association with the small molecule fluorophore
      DFHBI. Hybridization of a specific trigger oligonucleotide to a designed toehold
      leads to toehold-initiated strand displacement and refolds Spinach into the
      active, fluorophore-binding conformation. Spinach.ST not only specifically
      detects its target oligonucleotide but can discriminate readily against single
      nucleotide mismatches. RNA amplicons produced during nucleic acid sequence-based
      amplification (NASBA) of DNA or RNA targets could be specifically detected and
      reported in real-time by conformational activation of Spinach.ST generated by in
      vitro transcription. In order to adapt any target sequence to detection by a
      Spinach reporter we used a primer design technique that brings together otherwise
      distal toehold sequences via hairpin formation. The same techniques could
      potentially be used to adapt common Spinach reporters to non-nucleic acid
      analytes, rather than by making fusions between aptamers and Spinach. 

PMID- 24942629
TI  - iRGD tumor-penetrating peptide-modified oncolytic adenovirus shows enhanced tumor
      transduction, intratumoral dissemination and antitumor efficacy.
AB  - Endovenously administered oncolytic viruses extravasate and penetrate poorly into
      tumors. iRGD is a cyclic peptide that enhances tumor penetration when conjugated
      or coadministered with different types of molecules such as drugs, nanoparticles
      or phages. iRGD-mediated tumor penetration occurs in three steps: binding to
      alphav-integrins on tumor vasculature or tumor cells, exposure by proteolysis of
      a C-terminal motif that binds to neuropilin-1 (NRP-1) and cell internalization.
      We have genetically inserted the iRGD peptide in the fiber C terminus of
      ICOVIR15K, an oncolytic tumor-retargeted adenovirus to increase its tumor
      penetration. In vitro, NRP-1 interaction improved binding and internalization of
      the virus in different cancer cells overexpressing integrins and NRP-1. However,
      such NRP-1-mediated internalization did not affect transduction or cytotoxicity.
      In vivo, iRGD did not change the normal organ transduction pattern, with liver
      and spleen as main targeted organs. In tumors, however, iRGD enhanced
      transduction and early adenovirus dissemination through the tumor mass leading to
      an improved antitumor efficacy. 

PMID- 24942628
TI  - Exon skipping restores dystrophin expression, but fails to prevent disease
      progression in later stage dystrophic dko mice.
AB  - Antisense therapy with both chemistries of phosphorodiamidate morpholino
      oligomers (PMOs) and 2'-O-methyl phosphorothioate has demonstrated the capability
      to induce dystrophin expression in Duchenne muscular dystrophy (DMD) patients in
      phase II-III clinical trials with benefit in muscle functions. However, potential
      of the therapy for DMD at different stages of the disease progression is not
      understood. In this study, we examined the effect of peptide-conjugated PMO
      (PPMO)-mediated exon skipping on disease progression of utrophin-dystrophin
      deficient mice (dko) of four age groups (21-29, 30-39, 40-49 and 50+ days),
      representing diseases from early stage to advanced stage with severe kyphosis.
      Biweekly intravenous (i.v.) administration of the PPMO restored the dystrophin
      expression in nearly 100% skeletal muscle fibers in all age groups. This was
      associated with the restoration of dystrophin-associated proteins including
      functional glycosylated dystroglycan and neuronal nitric synthase. However,
      therapeutic outcomes clearly depended on severity of the disease at the time the
      treatment started. The PPMO treatment alleviated the disease pathology and
      significantly prolonged the life span of the mice receiving treatment at younger
      age with mild phenotype. However, restoration of high levels of dystrophin
      expression failed to prevent disease progression to the mice receiving treatment
      when disease was already at advanced stage. The results could be critical for
      design of clinical trials with antisense therapy to DMD. 

PMID- 24942630
TI  - Vero/BC-F: an efficient packaging cell line stably expressing F protein to
      generate single round-infectious human parainfluenza virus type 2 vector.
AB  - A stable packaging cell line (Vero/BC-F) constitutively expressing fusion (F)
      protein of the human parainfluenza virus type 2 (hPIV2) was established for
      production of the F-defective and single round-infectious hPIV2 vector in a
      strategy for recombinant vaccine development. The F gene expression has not
      evoked cytostatic or cytotoxic effects on the Vero/BC-F cells and the F protein
      was physiologically active to induce syncytial formation with giant
      polykaryocytes when transfected with a plasmid expressing hPIV2 hemagglutinin
      neuraminidase (HN). Transduction of the F-defective replicon RNA into the Vero/BC
      F cells led to the release of the infectious particles that packaged the replicon
      RNA (named as hPIV2DeltaF) without detectable mutations, limiting the infectivity
      to a single round. The maximal titer of the hPIV2DeltaF was 6.0 * 10(8) median
      tissue culture infections dose per ml. The influenza A virus M2 gene was inserted
      into hPIV2DeltaF, and the M2 protein was found to be highly expressed in a human
      lung cancer cell line after transduction. Furthermore, in vivo airway infection
      experiments revealed that the hPIV2DeltaF was capable of delivering transgenes to
      hamster tracheal cells. Thus, non-transmissible or single round-infectious hPIV2
      vector will be potentially applicable to human gene therapy or recombinant
      vaccine development. 

PMID- 24942632
TI  - Surgical resection of mesothelioma: an evidence-free practice.

PMID- 24942631
TI  - Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc
      pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open
      label, randomised, controlled trial.
AB  - BACKGROUND: Malignant pleural mesothelioma incidence continues to rise, with few
      available evidence-based therapeutic options. Results of previous non-randomised
      studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP)
      might improve symptom control and survival. We aimed to compare efficacy in terms
      of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with
      malignant pleural mesothelioma. METHODS: We undertook an open-label, parallel
      group, randomised, controlled trial in patients aged 18 years or older with any
      subtype of confirmed or suspected mesothelioma with pleural effusion, recruited
      from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to
      either VAT-PP or talc pleurodesis by computer-generated random numbers,
      stratified by European Organisation for Research and Treatment of Cancer risk
      category (high vs low). The primary outcome was overall survival at 1 year,
      analysed by intention to treat (all patients randomly assigned to a treatment
      group with a final diagnosis of mesothelioma). This trial is registered with
      ClinicalTrials.gov, number NCT00821860. FINDINGS: Between Oct 24, 2003, and Jan
      24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc
      pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival
      at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc
      pleurodesis group (hazard ratio 1.04 [95% CI 0.76-1.42]; p=0.81). Surgical
      complications were significantly more common after VAT-PP than after talc
      pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten
      (14%) of 73 patients who completed talc pleurodesis (p=0.019), as were
      respiratory complications (19 [24%] vs 11 [15%]; p=0.22) and air-leak beyond 10
      days (five [6%] vs one [1%]; p=0.21), although not significantly so. Median
      hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP
      compared with 3 days (2-5) for those who received talc pleurodesis (p<0.0001).
      INTERPRETATION: VAT-PP is not recommended to improve overall survival in patients
      with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis
      might be preferable considering the fewer complications and shorter hospital stay
      associated with this treatment. FUNDING: BUPA Foundation.

PMID- 24942633
TI  - An analytics approach to designing patient centered medical homes.
AB  - Recently the patient centered medical home (PCMH) model has become a popular team
      based approach focused on delivering more streamlined care to patients. In
      current practices of medical homes, a clinical based prediction frame is
      recommended because it can help match the portfolio capacity of PCMH teams with
      the actual load generated by a set of patients. Without such balances in clinical
      supply and demand, issues such as excessive under and over utilization of
      physicians, long waiting time for receiving the appropriate treatment, and non
      continuity of care will eliminate many advantages of the medical home strategy.
      In this paper, by using the hierarchical generalized linear model with
      multivariate responses, we develop a clinical workload prediction model for care
      portfolio demands in a Bayesian framework. The model allows for heterogeneous
      variances and unstructured covariance matrices for nested random effects that
      arise through complex hierarchical care systems. We show that using a
      multivariate approach substantially enhances the precision of workload
      predictions at both primary and non primary care levels. We also demonstrate that
      care demands depend not only on patient demographics but also on other
      utilization factors, such as length of stay. Our analyses of a recent data from
      Veteran Health Administration further indicate that risk adjustment for patient
      health conditions can considerably improve the prediction power of the model. 

PMID- 24942634
TI  - Natalizumab: risk stratification of individual patients with multiple sclerosis.
AB  - At present, three risk factors for the development of progressive multifocal
      leukoencephalopathy (PML) in natalizumab-treated patients have been identified:
      the presence of antibodies against JC virus (JCV); the duration of natalizumab
      treatment, especially if longer than 2 years; and the use of immunosuppressants
      prior to receiving natalizumab. The most commonly used strategy to assess the
      individual PML risk includes serum anti-JCV antibody testing. Based on the
      knowledge on all known risk factors, an algorithm for PML risk stratification has
      been proposed, where patients with the highest PML risk are those with positive
      anti-JCV antibodies, treatment duration longer than 2 years, with or without
      prior history of immunosuppression. These patients would have an approximate
      incidence of PML of 11.1 (with prior immunosuppression) or 4.6 (without prior
      immunosuppression) cases per 1,000 patients treated with natalizumab (and
      treatment duration longer than 2 years). In this review, new data on PML risk
      factors and possible new strategies for PML risk stratification are discussed.

PMID- 24942636
TI  - Characterization of Schizothorax prenanti cgnrhII gene: fasting affects cgnrhII
      expression.
AB  - In this study, the role of chicken gonadotropin-releasing hormone II (cgnrhII) in
      feeding regulation was investigated in Schizothorax prenanti. First, the full
      length S. prenanti cgnrhII cDNA consisted of 693 bp with an open reading frame of
      261 bp encoding a protein of 86 amino acids. Next, cgnrhII was widely expressed
      in the central and peripheral tissues. Last, there were significant changes in
      cgnrhII mRNA expression in the fasted group compared to the fed group in the S.
      prenanti hypothalamus during 24 h fasting (P < 0.05). Furthermore, the cgnrhII
      gene expression presented a significant decrease in the fasted group compared
      with the fed group (P < 0.05) on days 3, 5 and 7, after re-feeding, there was no
      significant changes in cgnrhII mRNA expression level between refed and fed group
      on day 9 (P > 0.05). Thus, the results suggest that cGnRH II expression is
      influenced by fasting and the gene may be involved in feeding regulation in S.
      prenanti.

PMID- 24942638
TI  - Factor Xa in mouse fibroblasts may induce fibrosis more than thrombin.
AB  - Coagulation factors are known to play a role in wound healing by stimulating
      fibroblasts and might be associated with tissue fibrosis, however, only limited
      data exist. Protease-activated receptor 1 (PAR1), activated by thrombin or factor
      (F) Xa, and PAR2, activated by FXa, have recently been reported to play roles not
      only in the coagulation system, but also in cardiac fibrosis. Furthermore, a
      previous report found that FX deficiency in mice led to the development of
      cardiac fibrosis. Therefore, in the present study, we evaluated cellular
      biological function under conditions of overexpressed thrombin and FXa in
      fibroblasts.Cell migration and proliferation with FXa (1U/mL) and thrombin
      (1U/mL) stimulation were evaluated. Cells incubated without FXa or thrombin were
      used as control. H2O2 and TGF-beta1 production were measured using ELISA. Signal
      pathways were evaluated using a signal pathway reporter assay.Cell migration and
      proliferation were increased in FXa-stimulated cells (4.1-fold increase for
      migration, 1.3-fold for proliferation compared with control, respectively) and
      thrombin (4.1-fold increase for migration, 1.3-fold for proliferation as compared
      to control, respectively). H2O2 production was higher in FXa-stimulated cells
      compared to thrombin (1.3-fold increase) and control cells (1.4-fold increased).
      TGF-beta1 production was up-regulated after FXa addition (12.6-fold increase
      compared with thrombin, 1.8-fold increase compared with control, respectively).
      In FXa-stimulated cells, AP-1 and NF-kB were increased compared to control (P <
      0.05).These data suggest that FXa and thrombin play important roles in the
      fibrotic process that could also lead to cardiac fibrosis, and that at least some
      of these signalings are more accelerated with FXa compared to thrombin. 

PMID- 24942637
TI  - Aberrant methylation of the VIM promoter in uterine cervical squamous cell
      carcinoma.
AB  - OBJECTIVES: To identify prognosis-associated methylation markers of uterine
      cervical squamous cell carcinoma (SCC) and to verify potential clinical
      correlations. METHODS: A genome-wide methylation array was performed using tissue
      samples of stage Ib1 (n = 9) and IIa (n = 5) tumors. Methylation levels were
      quantitatively evaluated by pyrosequencing for 54 tissue samples from SCC
      patients and 22 samples from normal controls. Clinicopathologic findings were
      obtained from medical records. Correlation or t test statistics were used to
      analyze the relationships between methylation levels and clinical features.
      Survival data were estimated using the Kaplan-Meier method and compared to the
      log-rank test. RESULTS: The methylation array identified 32 genes with distinct
      differences (p < 0.01) between stage Ib1 and IIa disease, and VIM was selected
      for further evaluation. Pyrosequencing analysis revealed that 40.7% of carcinoma
      samples had a higher methylation level in the VIM gene compared to the normal
      controls. VIM methylation status, low FIGO stage, and lack of parametrial
      involvement were significantly associated with longer disease-free survival (p =
      0.036, p = 0.028, and p = 0.001, respectively). CONCLUSIONS: We profiled 32 genes
      that might be associated with prognosis in cervical cancer. We further revealed
      that the VIM gene is frequently methylated in cervical SCC and that its
      methylation might predict a favorable prognosis.

PMID- 24942639
TI  - Nanoparticle-mediated drug delivery system for cardiovascular disease.
AB  - Administration of drugs and other therapeutic agents has been the central
      strategy of contemporary medicine for cardiovascular disease. The use of a drug
      delivery system (DDS) is always demanded to enhance the efficacy and safety of
      therapeutic agents, and improve the signal-to-noise ratio of imaging agents. Nano
      scale materials modify in vivo drug kinetics, depending on (patho)physiological
      mechanisms such as vascular permeability and incorporation by the mononuclear
      phagocyte system, which constitute 'passive-targeting' properties of nano-DDS. By
      contrast, an 'active-targeting' strategy employs a specific targeting structure
      on nano-DDS, which binds to the target molecule that is specific for a certain
      disease process, such as tumor specific antigens and the induction of adhesion
      molecules. In this review, we summarize recent studies that applied nano-DDS for
      the diagnosis and treatment of cardiovascular disease, especially focusing on
      atherosclerosis and myocardial ischemia-reperfusion (IR) injury.
      Pathophysiological changes in atherosclerosis and myocardial IR injury are
      successfully targeted by nano-DDS and preclinical studies in animals showed
      positive effects of nano-DDS enhancing efficacy and reducing adverse effects. The
      development of nano-DDS in clinical medicine is keenly being awaited. 

PMID- 24942635
TI  - Orexin/hypocretin based pharmacotherapies for the treatment of addiction: DORA or
      SORA?
AB  - Addiction is a chronic relapsing disorder which presents a significant global
      health burden and unmet medical need. The orexin/hypocretin system is an
      attractive potential therapeutic target as demonstrated by the successful
      clinical trials of antagonist medications like Suvorexant for insomnia. It is
      composed of two neuropeptides, orexin-A and orexin-B and two excitatory and
      promiscuous G-protein coupled receptors, OX1 and OX2. Orexins are known to have a
      variety of functions, most notably in regulating arousal, appetite and reward.
      The orexins have been shown to have a role in mediating the effects of several
      drugs of abuse, such as cocaine, morphine and alcohol via projections to key
      brain regions such as the ventral tegmental area, nucleus accumbens and
      prefrontal cortex. However, it has not yet been demonstrated whether the dual
      orexin receptor antagonists (DORAs) under development for insomnia are ideal
      drugs for the treatment of addiction. The question of whether to use a DORA or
      single orexin receptor antagonist (SORA) for the treatment of addiction is a key
      question that will need to be answered in order to maximize the clinical utility
      of orexin receptor antagonists. This review will examine the role of the
      orexin/hypocretin system in addiction, orexin-based pharmacotherapies under
      development and factors affecting the selection of one or both orexin receptors
      as drug targets for the treatment of addiction. 

PMID- 24942641
TI  - Molecular basis of the selective binding of MDMA enantiomers to the alpha4beta2
      nicotinic receptor subtype: synthesis, pharmacological evaluation and mechanistic
      studies.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is a molecular target of
      3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug also known as ecstasy,
      and it modulates the MDMA-mediated reinforcing properties. However, the
      enantioselective preference of the alpha4beta2 nAChR subtype still remains
      unknown. Since the two enantiomers exhibit different pharmacological profiles and
      stereoselective metabolism, the aim of this study is to assess a possible
      difference in the interaction of the MDMA enantiomers with this nAChR subtype. To
      this end, we report a novel simple, yet highly efficient enantioselective
      synthesis of the MDMA enantiomers, in which the key step is the
      diastereoselective reduction of imides derived from optically pure tert
      butylsulfinamide. The enantioselective binding to the receptor is examined using
      [(3)H]epibatidine in a radioligand assay. Even though the two enantiomers induced
      a concentration-dependent binding displacement, (S)-MDMA has an inhibition
      constant 13-fold higher than (R)-MDMA, which shows a Hill's coefficient not
      significantly different from unity, implying a competitive interaction.
      Furthermore, when NGF-differentiated PC12 cells were pretreated with the
      compounds, a significant increase in binding of [(3)H]epibatidine was found for
      (R)-MDMA, indicating up-regulation of heteromeric nAChR in the cell surface.
      Finally, docking and molecular dynamics studies have been used to identify the
      binding mode of the two enantiomers, which provides a structural basis to justify
      the differences in affinity from the differential interactions played by the
      substituents at the stereogenic centre of MDMA. The results provide a basis to
      explore the distinct psychostimulant profiles of the MDMA enantiomers mediated by
      the alpha4beta2 nAChR subtype. 

PMID- 24942640
TI  - Clinicopathological features and prognostic factors of young breast cancers in
      Eastern Guangdong of China.
AB  - Breast cancer in young women is typically with higher proportion of adverse
      pathological features. Breast cancer with BRCA1 mutation is often early-onset,
      and is usually associated with triple negative phenotpe. In this study, we aim to
      analyze the clinicopathological characteristics and prognosis in young breast
      cancer patients (<=35 years old) comparing to non-young patients (>35 years old).
      A total of 1913 cases of primary breast carcinoma with stage I-III were enrolled,
      with 283 cases diagnosed as young patients. No significant difference was
      observed in tumor size, TNM staging, lymph node metastasis, ER, HER-2 or
      histological grade between young and non-young patients. Multivariate analysis
      demonstrated that age was an independent prognostic factor for overall survival
      (OS). In 70 samples of young patients available, BRCA1 was immunohistochemically
      positive 85.7% in cytoplasm and 41.4% in nuclear. BRCA1 nuclear expression is not
      significantly associated with clinicopathological characteristics in young breast
      cancer patients. 

PMID- 24942642
TI  - Stability of luminescence in LaPO4, LaPO4 :RE(3+) (RE = Dy, Eu) nanophosphors.
AB  - The property of high refractive index, low solubility in water as well as
      stability to high temperature variation of lanthanum phosphate (LaPO4 ) proved it
      was the most effective candidate for the production of display lamps, and plasma
      display panel devices and sensors. The morphological and nanostructural
      characteristics play a key role in the working efficiency of the luminescent
      material. These properties can be controlled by the synthesis method, which we
      have adopted in this paper. We have prepared LaPO4 nanoparticles at a relatively
      low temperature (110 oC) in polyethylene glycol medium by using a wet chemical
      one-step synthesis. The phase composition and structural properties of the sample
      have been characterized by X-ray diffraction, Fourier transform infrared,
      transmission electron microscopy and the luminescent property by
      photoluminescence and thermoluminescence. The samples were well crystallized and
      the average crystallite size of 15 nm has been calculated for pure LaPO4 using
      the Debye-Scherrer equation. The result from heat-treated samples shows the phase
      combination and morphological structure of the powder depend on the annealing
      temperature. The heat treatment changes the structure of LaPO4 from cuboid rods
      to fine grains at about 600  degrees C. The emission spectrum of LaPO4 shows the
      broad emission band at 368 nm and shoulder at 465 nm with emission of blue color
      when monitored at an excitation wavelength at 256 nm. The stability of phosphor
      has been studied with respect to humidity, temperature, doping, doping
      concentration, gamma-ray exposures, etc. The prepared nanosized phosphors were
      thermally stable and may be a promising blue phosphor for lighting technology as
      well as radiation dosimetry.

PMID- 24942643
TI  - Association of FLOWERING LOCUS T/TERMINAL FLOWER 1-like gene FTL2 expression with
      growth rhythm in Scots pine (Pinus sylvestris).
AB  - Understanding the genetic basis of the timing of bud set, an important trait in
      conifers, is relevant for adaptation and forestry practice. In common garden
      experiments, both Scots pine (Pinus sylvestris) and Norway spruce (Picea abies)
      show a latitudinal cline in the trait. We compared the regulation of their bud
      set biology by examining the expression of PsFTL2, a Pinus sylvestris homolog to
      PaFTL2, a FLOWERING LOCUS T/TERMINAL FLOWER 1 (FT/TFL1)-like gene, the expression
      levels of which have been found previously to be associated with the timing of
      bud set in Norway spruce. In a common garden study, we analyzed the relationship
      of bud phenology under natural and artificial photoperiods and the expression of
      PsFTL2 in a set of Scots pine populations from different latitudes. The
      expression of PsFTL2 increased in the needles preceding bud set and decreased
      during bud burst. In the northernmost population, even short night periods were
      efficient to trigger this expression, which also increased earlier under all
      photoperiodic regimes compared with the southern populations. Despite the
      different biology, with few limitations, the two conifers that diverged 140
      million yr ago probably share an association of FTL2 with bud set, pointing to a
      common mechanism for the timing of growth cessation in conifers. 

PMID- 24942645
TI  - Effect of temporal acquisition parameters on image quality of strain time
      constant elastography.
AB  - Ultrasound methods to image the time constant (TC) of elastographic tissue
      parameters have been recently developed. Elastographic TC images from creep or
      stress relaxation tests have been shown to provide information on the
      viscoelastic and poroelastic behavior of tissues. However, the effect of temporal
      ultrasonic acquisition parameters and input noise on the image quality of the
      resultant strain TC elastograms has not been fully investigated yet.
      Understanding such effects could have important implications for clinical
      applications of these novel techniques. This work reports a simulation study
      aimed at investigating the effects of varying windows of observation, acquisition
      frame rate, and strain signal-to-noise ratio (SNR) on the image quality of
      elastographic TC estimates. A pilot experimental study was used to corroborate
      the simulation results in specific testing conditions. The results of this work
      suggest that the total acquisition time necessary for accurate strain TC
      estimates has a linear dependence to the underlying strain TC (as estimated from
      the theoretical strain-vs.-time curve). The results also indicate that it might
      be possible to make accurate estimates of the elastographic TC (within 10% error)
      using windows of observation as small as 20% of the underlying TC, provided
      sufficiently fast acquisition rates (>100 Hz for typical acquisition depths). The
      limited experimental data reported in this study statistically confirm the
      simulation trends, proving that the proposed model can be used as upper bound
      guidance for the correct execution of the experiments. 

PMID- 24942644
TI  - Lack of a practical system to respond to domestic violence.

PMID- 24942646
TI  - Selenium supplementation in patients undergoing hematopoietic stem cell
      transplantation: effects on pro-inflammatory cytokines levels.
AB  - BACKGROUND: Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF
      alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) play an important
      role in the development of hematopoietic stem cell transplantation (HSCT)
      complications. We explored the effect of Selenium as an antioxidant and anti
      inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates.
      FINDINGS: Plasma concentrations of TNF-alpha, IL-1beta and IL-6 were measured in
      74 patients from a double-blind, randomized, placebo-controlled study. In both
      groups, there were 37 patients with median age of 32 years. Patients received
      oral Se tablets (200 mcg) or placebo twice daily beginning from the first day of
      high dose chemotherapy (HDC) through 14 days after HSCT. Cytokine levels were
      determined before starting HDC (prior to first dose of Se), 7 and 14 days after
      HSCT. Plasma levels of TNF-alpha were not significantly different between Se and
      control group (P = 0.13). IL-1 levels were similar between two groups (P = 0.88).
      No significant differences were detected in IL-6 levels between Se and control
      group (P = 0.96). CONCLUSION: Selenium had no effect on pro-inflammatory
      cytokines levels in patients undergoing HSCT. It is likely that earlier
      initiation and/or larger doses of Se are required to affect inflammatory
      cytokines significantly.

PMID- 24942649
TI  - Straining Psychic and Social Sinew: Trauma among Adolescent Psychiatric Patients
      in New Mexico.
AB  - Drawing on data from a longitudinal study of 47 adolescents of diverse ethnic
      backgrounds hospitalized for psychiatric disorder in New Mexico, the article
      critically examines the relevance of post-traumatic stress disorder (PTSD) to
      address anthropological questions of how to define the problem. Factors include
      the utility/limitation of psychiatric diagnostic categories, the lived experience
      of severe distress, the socioeconomic and political conditions of suffering, and
      reciprocal relations between immediate and remote social institutions. I discuss
      the mental health care system for adolescents and present two case studies of
      young inpatients, emphasizing the need for dual specification of the conditions
      of trauma and the structure of experience. I argue for understanding patterns of
      abandonment that shape the raw existence of young people at both the personal and
      collective levels to apprehend their depth and durability. 

PMID- 24942647
TI  - Unrelated solubility-enhancing fusion partners MBP and NusA utilize a similar
      mode of action.
AB  - The tendency of recombinant proteins to accumulate in the form of insoluble
      aggregates in Escherichia coli is a major hindrance to their overproduction. One
      of the more effective approaches to circumvent this problem is to use translation
      fusion partners {solubility-enhancers (SEs)}. E. coli maltose-binding protein
      (MBP) and N-utilization substance A (NusA) are arguably the most effective
      solubilizing agents that have been discovered so far. Here, we show that although
      these two proteins are structurally, functionally, and physicochemically
      distinct, they influence the solubility and folding of their fusion partners in a
      very similar manner. These SEs act as "holdases" that prevent the aggregation of
      their fusion partners. Subsequent folding of the passenger proteins, when it
      occurs, is either spontaneous or chaperone-mediated.

PMID- 24942650
TI  - Effects of smoking and shared epitope on the production of anti-citrullinated
      peptide antibody in a Japanese adult population.
AB  - OBJECTIVE: Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF)
      are markers to rheumatoid arthritis (RA). Smoking and shared epitope (SE) in HLA
      DRB1 are associated with the production of these autoantibodies in RA. Detailed
      distribution and characterization of ACPA and RF in the general population have
      remained unclear. We aimed to evaluate positivity of ACPA and RF in a general
      Japanese population and to detect correlates, including genetic components.
      METHODS: ACPA and RF were quantified in 9,804 Japanese volunteers ages 30-75
      years. Logistic regression analyses were performed to evaluate the effects of
      candidates of correlates on the autoantibody positivity. A genome-wide
      association study (GWAS) was performed using 394,239 single nucleotide
      polymorphisms for 3,170 participants, and HLA-DRB1 alleles were imputed based on
      the GWAS data. RESULTS: A total of 1.7% and 6.4% of subjects were positive for
      ACPA and RF, respectively, and the 2 markers showed a significant correlation (P
      = 2.0 * 10(-23) ). Old age was associated with ACPA positivity (P = 0.00062).
      Sex, smoking, SE, and other candidates of correlates did not have significant
      effects. Interaction between smoking and SE positivity was not apparent, but
      smoking showed a significant association with high levels of ACPA (P = 0.0019).
      CONCLUSION: ACPA and RF could be detected in 1.7% and 6.4% of the Japanese adult
      population without RA, respectively. ACPA and RF were suggested to share
      mechanisms even in healthy populations. Old age was associated with increasing
      ACPA positivity. While positivity of ACPA and RF was not associated with SE and
      smoking, an association between high ACPA and smoking was observed.

PMID- 24942648
TI  - Irreversible perinatal imprinting of adult expression of the principal sex
      dependent drug-metabolizing enzyme CYP2C11.
AB  - We proposed to determine whether, like other sexual dimorphisms, drug metabolism
      is permanently imprinted by perinatal hormones, resulting in its irreversible sex
      dependent expression. We treated newborn male rats with monosodium glutamate
      (MSG), a total growth hormone (GH) blocker, and, using cultured hepatocytes,
      examined expression of adult CYP2C11, the predominant cytochrome-P450 expressed
      only in males, as well as the signal transduction pathway by which episodic GH
      solely regulates the isoform's expression. In addition, adolescent
      hypophysectomized (hypox) male rats served as controls in which GH was eliminated
      after the critical imprinting period. Whereas renaturalization of the masculine
      episodic GH profile restored normal male-like levels of CYP2C11, as well as
      CYP2C12, in hepatocytes from hypox rats, the cells derived from the MSG-treated
      rats were completely unresponsive. Moreover, GH exposure of hepatocytes from
      hypox rats resulted in normal induction, activation, nuclear translocation, and
      binding to the CYP2C11 promoter of the signal transducers mediating GH regulation
      of CYP2C11 expression, which dramatically contrasted with the complete
      unresponsiveness of the MSG-derived hepatocytes, also associated with
      hypermethylation of GH-response elements in the CYP2C11 promoter. Lastly,
      neonatal MSG treatment had no adverse effect on postnatal and adult testosterone
      levels. The results demonstrate that the sexually dimorphic expression of CYP2C11
      is irreversibly imprinted shortly after birth by a hormone other than the
      customary testosterone, but likely by GH.

PMID- 24942652
TI  - "Back to the future" or iron in the MS brain - commentary on "perivascular iron
      deposits are associated with protein nitration in cerebral experimental
      autoimmune encephalomyelitis".

PMID- 24942651
TI  - Genomic comparative analysis of the environmental Enterococcus mundtii against
      enterococcal representative species.
AB  - BACKGROUND: Enterococcus mundtii is a yellow-pigmented microorganism rarely found
      in human infections. The draft genome sequence of E. mundtii was recently
      announced. Its genome encodes at least 2,589 genes and 57 RNAs, and 4 putative
      genomic islands have been detected. The objective of this study was to compare
      the genetic content of E. mundtii with respect to other enterococcal species and,
      more specifically, to identify genes coding for putative virulence traits present
      in enterococcal opportunistic pathogens. RESULTS: An in-depth mining of the
      annotated genome was performed in order to uncover the unique properties of this
      microorganism, which allowed us to detect a gene encoding the antimicrobial
      peptide mundticin among other relevant features. Moreover, in this study a
      comparative genomic analysis against commensal and pathogenic enterococcal
      species, for which genomic sequences have been released, was conducted for the
      first time. Furthermore, our study reveals significant similarities in gene
      content between this environmental isolate and the selected enterococci strains
      (sharing an "enterococcal gene core" of 805 CDS), which contributes to understand
      the persistence of this genus in different niches and also improves our knowledge
      about the genetics of this diverse group of microorganisms that includes
      environmental, commensal and opportunistic pathogens. CONCLUSION: Although E.
      mundtii CRL1656 is phylogenetically closer to E. faecium, frequently responsible
      of nosocomial infections, this strain does not encode the most relevant relevant
      virulence factors found in the enterococcal clinical isolates and bioinformatic
      predictions indicate that it possesses the lowest number of putative pathogenic
      genes among the most representative enterococcal species. Accordingly, infection
      assays using the Galleria mellonella model confirmed its low virulence.

PMID- 24942654
TI  - The synthesis and structure of [Zn(TEMPO)2]2 and [Zn(MU-H)(MU(2)-eta(1):eta(1)
      TEMPO)]6.
AB  - The commercially available radical TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxy)
      reacts with [ZnCp*2] (1) to yield the homoleptic compound [Zn(TEMPO)2]2 (2)
      through coupling of two Cp* radicals. Compound 1 reacts with H2 to afford the
      hydride complex [Zn(MU-H)(MU(2)-eta(1)-eta(1)-TEMPO)]6 (3) featuring a planar
      Zn6H6 ring in the solid state. Preliminary data suggest that the formation of 3
      proceeds via a radical mechanism.

PMID- 24942653
TI  - Nonabsorbable suture granuloma mimicking ovarian cancer recurrence at combined
      positron emission tomography/computed tomography evaluation: a case report.
AB  - INTRODUCTION: This is the first case of suture granuloma mimicking isolated
      ovarian cancer relapse. Only six analogous cases have been previously reported in
      other malignancies. CASE PRESENTATION: We report the case of a 44-year-old
      Caucasian woman with partially platinum-sensitive ovarian cancer in which
      radiological features, including computed tomography and combined 18F
      fluorodeoxyglucose-positron emission tomography/computed tomography, were
      strongly suggestive of isolated cancer relapse in her right subdiaphragmatic
      region. Laparoscopic examination resulted negative, but was not completely
      suitable due to widespread adhesive syndrome. The laparotomy for secondary
      cytoreductive surgery and biopsy of the suspected area showed inflammatory
      granuloma caused by nonabsorbable propylene suture, without evidence of
      neoplastic cells. Moreover, unexpected peritoneal carcinosis was found.
      CONCLUSIONS: This evidence suggests that clinical details about previous surgical
      procedures are necessary for adequate interpretation. Although much progress has
      been made in imaging techniques, especially in the promising field of combined
      18F-fluorodeoxyglucose positron emission tomography/computed tomography, these
      procedures should be still thoroughly investigated in order to promptly rule out
      tumor recurrence and avoid unnecessary surgery.

PMID- 24942659
TI  - Editorial: Writing a helpful journal review: application of the 6 C's.

PMID- 24942655
TI  - Adaptor bypass mutations of Bacillus subtilis spx suggest a mechanism for YjbH
      enhanced proteolysis of the regulator Spx by ClpXP.
AB  - The global regulator, Spx, is under proteolytic control exerted by the adaptor
      YjbH and ATP-dependent protease ClpXP in Bacillus subtilis. While YjbH is
      observed to bind the Spx C-terminus, YjbH shows little affinity for ClpXP,
      indicating adaptor activity that does not operate by tethering. Chimeric proteins
      derived from B. subtilis AbrB and the Spx C-terminus showed that a 28-residue C
      terminal section of Spx (AbrB28), but not the last 12 or 16 residues (AbrB12,
      AbrB16), was required for YjbH interaction and for ClpXP proteolysis, although
      the rate of AbrB28 proteolysis was not affected by YjbH addition. The result
      suggested that the YjbH-targeted 28 residue segment of the Spx C-terminus bears a
      ClpXP-recognition element(s) that is hidden in the intact Spx protein. Residue
      substitutions in the conserved helix alpha6 of the C-terminal region generated
      Spx substrates that were degraded by ClpXP at accelerated rates compared to wild
      type Spx, and showed reduced dependency on the YjbH activity. The residue
      substitutions also weakened the interaction between Spx and YjbH. The results
      suggest a model in which YjbH, through interaction with residues of helix alpha6,
      exposes the C-terminus of Spx for recognition and proteolysis by ClpXP. 

PMID- 24942660
TI  - Titanium dioxide-montmorillonite nanocomposite as photoprotective agent against
      ultraviolet B radiation-induced mutagenesis in Saccharomyces cerevisiae: a
      potential candidate for safer sunscreens.
AB  - Photoprotective potential and biological consequences (mutagenic potential) of
      octyl-dimethyl-PABA (ODP), titanium dioxide (TiO2 ), and montmorillonite (MMT)
      upon ultraviolet B (UVB) irradiation, alone and in different associations
      [physical mixtures (PMs)], were evaluated using a Saccharomyces cerevisiae ogg1
      mutant (deficient) strain. In addition, we developed and characterized a
      delaminated TiO2-pillared MMT, called the TiO2 -MMT nanocomposite (NC), which was
      also investigated in terms of its photoprotective and mutagenic potential.
      Overall, our results revealed an interesting TiO2 -MMT NC endowed with
      antimutagenic activity that can be associated to organic sunscreen molecule (ODP)
      and still maintain its positive effect, whereas its respective PM is unable to
      grant antimutagenic protection against UVB.

PMID- 24942661
TI  - Tocilizumab-induced psoriasiform rash in rheumatoid arthritis.
AB  - Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin-6
      (IL-6) receptor and has been approved for the treatment of rheumatoid arthritis
      (RA) patients who have had an inadequate response to previous biological
      therapies. Psoriasiform skin lesions, especially palmoplantar pustulosis lesions,
      are well described following anti-tumour necrosis factor therapy. We describe a
      79-year-old woman with rheumatoid factor-positive, anti-citrullinated protein
      antibody-positive erosive RA, who developed a psoriasiform palmoplantar
      pustulosis reaction following treatment with TCZ therapy (IL-6 receptor). The
      rash showed histological features compatible with psoriasis and disappeared
      following discontinuation of TCZ.

PMID- 24942662
TI  - Quality of physical therapy from a patient's perspective; factor analysis on web
      based survey data revealed three dimensions on patient experiences with physical
      therapy.
AB  - BACKGROUND: Assessing quality of care from the patient's perspective has changed
      from patient satisfaction to the more general term patient experience, as
      satisfaction measures turned out to be less discriminative due to high scores.
      Literature describes four to ten dimensions of patient experience, tailored to
      specific conditions or types of care. Given the administrative burden on
      patients, less dimensions and items could increase feasibility. Ten dimensions of
      patient experiences with physical therapy (PT) were proposed in the Netherlands
      in a consensus-based process with patients, physical therapists, health insurers,
      and policy makers. The aim of this paper is to detect the number of dimensions
      from data of a field study using factor analysis at item level. METHODS: A web
      based survey yielded data of 2,221 patients from 52 PT practices on 41 items.
      Principal component factor analysis at item level was used to assess the proposed
      distinction between the ten dimensions. RESULTS: Factor analysis revealed two
      dimensions: 'personal interaction' and 'practice organisation'. The dimension
      'patient reported outcome' was artificially established. The three dimensions
      'personal interaction' (14 items) (median(practice level) = 91.1; IQR = 2.4),
      'practice organisation' (9 items) (median(practice level) = 88.9; IQR = 6.0) and
      'outcome' (3 items) (median(practice level) = 80.6; IQR = 19.5) reduced the
      number of dimensions from ten to three and the number of items by more than a
      third. CONCLUSIONS: Factor analysis revealed three dimensions and achieved an
      item reduction of more than a third. It is a relevant step in the development
      process of a quality measurement tool to reduce respondent burden, increase
      clarity, and promote feasibility.

PMID- 24942656
TI  - 18F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time
      intervals derived from a single-institution 18F-FDG-directed surgery experience:
      feasibility and quantification of 18F-FDG accumulation within 18F-FDG-avid
      lesions and background tissues.
AB  - BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission
      tomography/computed tomography (PET/CT) is a well-established imaging modality
      for a wide variety of solid malignancies. Currently, only limited data exists
      regarding the utility of PET/CT imaging at very extended injection-to-scan
      acquisition times. The current retrospective data analysis assessed the
      feasibility and quantification of diagnostic (18)F-FDG PET/CT oncologic imaging
      at extended injection-to-scan acquisition time intervals. METHODS: (18)F-FDG-avid
      lesions (not surgically manipulated or altered during (18)F-FDG-directed surgery,
      and visualized both on preoperative and postoperative (18)F-FDG PET/CT imaging)
      and corresponding background tissues were assessed for (18)F-FDG accumulation on
      same-day preoperative and postoperative (18)F-FDG PET/CT imaging. Multiple
      patient variables and (18)F-FDG-avid lesion variables were examined. RESULTS: For
      the 32 (18)F-FDG-avid lesions making up the final (18)F-FDG-avid lesion data set
      (from among 7 patients), the mean injection-to-scan times of the preoperative and
      postoperative (18)F-FDG PET/CT scans were 73 (+/- 3, 70-78) and 530 (+/- 79, 413
      739) minutes, respectively (P < 0.001). The preoperative and postoperative mean
      (18)F-FDG-avid lesion SUV(max) values were 7.7 (+/- 4.0, 3.6-19.5) and 11.3 (+/-
      6.0, 4.1-29.2), respectively (P < 0.001). The preoperative and postoperative mean
      background SUV(max) values were 2.3 (+/- 0.6, 1.0-3.2) and 2.1 (+/- 0.6, 1.0
      3.3), respectively (P = 0.017). The preoperative and postoperative mean lesion-to
      background SUV(max) ratios were 3.7 (+/- 2.3, 1.5-9.8) and 5.8 (+/- 3.6, 1.6
      16.2), respectively, (P < 0.001). CONCLUSIONS: (18)F-FDG PET/CT oncologic imaging
      can be successfully performed at extended injection-to-scan acquisition time
      intervals of up to approximately 5 half-lives for (18)F-FDG while maintaining
      good/adequate diagnostic image quality. The resultant increase in the (18)F-FDG
      avid lesion SUV(max) values, decreased background SUV(max) values, and increased
      lesion-to-background SUV(max) ratios seen from preoperative to postoperative
      (18)F-FDG PET/CT imaging have great potential for allowing for the integrated,
      real-time use of (18)F-FDG PET/CT imaging in conjunction with (18)F-FDG-directed
      interventional radiology biopsy and ablation procedures and (18)F-FDG-directed
      surgical procedures, as well as have far-reaching impact on potentially re
      shaping future thinking regarding the "most optimal" injection-to-scan
      acquisition time interval for all routine diagnostic (18)F-FDG PET/CT oncologic
      imaging.

PMID- 24942663
TI  - Analytic Element Modeling of Steady Interface Flow in Multilayer Aquifers Using
      AnAqSim.
AB  - This paper presents the analytic element modeling approach implemented in the
      software AnAqSim for simulating steady groundwater flow with a sharp fresh-salt
      interface in multilayer (three-dimensional) aquifer systems. Compared with
      numerical methods for variable-density interface modeling, this approach allows
      quick model construction and can yield useful guidance about the three
      dimensional configuration of an interface even at a large scale. The approach
      employs subdomains and multiple layers as outlined by Fitts (2010) with the
      addition of discharge potentials for shallow interface flow (Strack 1989). The
      following simplifying assumptions are made: steady flow, a sharp interface
      between fresh- and salt water, static salt water, and no resistance to vertical
      flow and hydrostatic heads within each fresh water layer. A key component of this
      approach is a transition to a thin fixed minimum fresh water thickness mode when
      the fresh water thickness approaches zero. This allows the solution to converge
      and determine the steady interface position without a long transient simulation.
      The approach is checked against the widely used numerical codes SEAWAT and
      SWI/MODFLOW and a hypothetical application of the method to a coastal wellfield
      is presented. 

PMID- 24942665
TI  - Synthetic glycosylated natural products have satisfactory activities.
AB  - Many natural products contain sugar residues, which are essential components for
      great medicinal importance. The sugar moieties can improve water-solubility of
      natural products and decrease their toxicity. At the same time, the glycosidic
      residues are crucial for the activities of natural products. Much effort has been
      expended over the past decades in developing novel and efficient methodologies to
      synthesize the glycosylated natural products. This review highlights recent
      developments in the synthesis of glycosylated natural products. The structure
      activity relationships of some of these glycosylated natural products, together
      with the structure characteristics of their interaction with the biological
      targets, are also involved. 

PMID- 24942664
TI  - Quantification of bacterial and archaeal symbionts in high and low microbial
      abundance sponges using real-time PCR.
AB  - In spite of considerable insights into the microbial diversity of marine sponges,
      quantitative information on microbial abundances and community composition
      remains scarce. Here, we established qPCR assays for the specific quantification
      of four bacterial phyla of representative sponge symbionts as well as the
      kingdoms Eubacteria and Archaea. We could show that the 16S rRNA gene numbers of
      Archaea, Chloroflexi, and the candidate phylum Poribacteria were 4-6 orders of
      magnitude higher in high microbial abundance (HMA) than in low microbial
      abundance (LMA) sponges and that actinobacterial 16S rRNA gene numbers were 1-2
      orders higher in HMA over LMA sponges, while those for Cyanobacteria were stable
      between HMA and LMA sponges. Fluorescence in situ hybridization of Aplysina
      aerophoba tissue sections confirmed the numerical dominance of Chloroflexi, which
      was followed by Poribacteria. Archaeal and actinobacterial cells were detected in
      much lower numbers. By use of fluorescence-activated cell sorting as a primer-
      and probe-independent approach, the dominance of Chloroflexi, Proteobacteria, and
      Poribacteria in A. aerophoba was confirmed. Our study provides new quantitative
      insights into the microbiology of sponges and contributes to a better
      understanding of the HMA/LMA dichotomy. 

PMID- 24942666
TI  - Efficacy of fluconazole at a 400 mg weekly dose for the treatment of
      onychomycosis.

PMID- 24942668
TI  - Editorial comment from Dr Kono to Impact of graft nephrectomy on outcomes of
      second kidney transplantation.

PMID- 24942669
TI  - Sustained Wnt/beta-catenin signalling causes neuroepithelial aberrations through
      the accumulation of aPKC at the apical pole.
AB  - beta-Catenin mediates the canonical Wnt pathway by stimulating Tcf-dependent
      transcription and also associates to N-cadherin at the apical complex (AC) of
      neuroblasts. Here, we show that while beta-catenin activity is required to form
      the AC and to maintain the cell polarity, oncogenic mutations that render stable
      forms of beta-catenin (sbeta-catenin) maintain the stemness of neuroblasts,
      inhibiting their differentiation and provoking aberrant growth. In examining the
      transcriptional and structural roles of beta-catenin, we find that while beta
      catenin/Tcf transcriptional activity induces atypical protein kinase C (aPKC)
      expression, an alternative effect of beta-catenin restricts aPKC to the apical
      pole of neuroepithelial cells. In agreement, we show that a constitutively active
      form of aPKC reproduces the neuroepithelial aberrations induced by beta-catenin.
      Therefore, we conclude that beta-catenin controls the cell fate and polarity of
      the neuroblasts through the expression and localization of aPKC. 

PMID- 24942670
TI  - Synthesis of phosphaisocoumarin amidates via DIBAL-H-mediated selective amidation
      of phosphaisocoumarin esters.
AB  - A series of phosphaisocoumarin amidates were synthesized for the first time via
      DIBAL-H-mediated direct amidation of phosphaisocoumarin esters under mild
      conditions in good to excellent yields. The present reaction showed high
      selectivity. In each case, the phostone ring was intact and only the exocyclic
      ethoxy group was amidated. A plausible mechanism of the reaction was provided. 

PMID- 24942671
TI  - A nitride based polarization-engineered photocathode for water splitting without
      a p-type semiconductor.
AB  - Photoelectrochemical water splitting is a promising way for hydrogen production
      with low environmental burden. Although III-nitride semiconductors have
      potentially favorable properties as water splitting photoelectrodes, they have
      several limitations for practical use currently. In this study, the concept of a
      polarization-engineered nitride photocathode for water splitting is proposed to
      overcome this problem. We observed that the proposed GaN/AlN/GaN structure worked
      as a photocathode even though it consisted of only n-type III-nitride
      semiconductors. This polarization-engineered photocathode showed a remarkably
      stable and relatively high photocurrent since it can avoid the causes of problems
      from which both n-type and p-type conventional GaN photoelectrodes suffer. 

PMID- 24942672
TI  - A Bayesian model averaging approach to examining changes in quality of life among
      returning Iraq and Afghanistan veterans.
AB  - Many Veterans from the conflicts in Iraq and Afghanistan return home with
      physical and psychological impairments that impact their ability to enjoy normal
      life activities and diminish their quality of life (QoL). The present research
      aimed to identify predictors of QoL over an eight-month period using Bayesian
      model averaging (BMA), which is a statistical technique useful for maximizing
      power with smaller sample sizes. A sample of 117 Iraq and Afghanistan Veterans
      receiving care in a southwestern health care system was recruited, and BMA
      examined the impact of key demographics (e.g., age, gender), diagnoses (e.g.,
      depression), and treatment modalities (e.g., individual therapy, medication) on
      QoL over time. Multiple imputation based on Gibbs sampling was employed for
      incomplete data (6.4% missingness). Average follow-up QoL scores were
      significantly lower than at baseline (73.2 initial versus 69.5 four-month and
      68.3 eight-month). Employment was associated with increased QoL during each
      follow-up, while post-traumatic stress disorder and Black race were inversely
      related. Additionally, predictive models indicated that depression, income,
      treatment for a medical condition, and group psychotherapy were strong negative
      predictors of four-month QoL but not eight-month QoL.

PMID- 24942673
TI  - Relative importance of indigenous medicinal plants from Layyah district, Punjab
      Province, Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnomedicinal reports are important for the
      discovery of new crude drugs from reported medicinal plants with high use value.
      The current study aimed to document the medicinal flora as well as medicinal
      knowledge of indigenous plants of local communities from Layyah district, Punjab
      Province, Pakistan. MATERIAL AND METHODS: Rapid appraisal approach (RAA), semi
      structured interviews, group meetings with herbalists, landowners and local
      people having awareness about the medicinal action of plants were employed to
      collect the data. Use values (UV) and frequency of citation (FC) were calculated
      to check the relative importance of plants. RESULTS AND DISCUSSIONS: The current
      ethnomedicinal study reported 125 medicinal plant species diversified from 106
      genus belonging to the 43 different families and Poaceae was the predominant
      family over others with 16 reported medicinal plants. Wild herbaceous plants were
      the predominant over other life forms while among plant parts, leaves contributed
      32% followed by the stem (27%), fruit and flowers (15%). Allium sativum exhibited
      the highest use vale (UV) 0.92 while the lowest UV was exhibited by Lasiurus
      scindicus which was 0.15. CONCLUSION: Local communities of district Layyah still
      have a strong faith on herbal medicines for basic healthcare needs. Indigenous
      plants having high UV and FC should be subjected to the detailed phytochemical
      investigations to explore new natural drugs.

PMID- 24942674
TI  - Variations in body weight, food intake and body composition after long-term high
      fat diet feeding in C57BL/6J mice.
AB  - OBJECTIVE: To investigate the variations in body weight, food intake, and body
      composition of both male and female C57BL/6J mice during a diet-induced obesity
      model with high-fat diet (HFD) feeding. METHODS: Mice were individually housed
      and fed ad libitum either a low-fat diet (LFD, 10% calories from fat; n = 15
      male, n = 15 female) or HFD (45% calories from fat; n = 277 male, n = 278 female)
      from 8 to 43 weeks of age. Body weight, food intake, and body composition were
      routinely measured. RESULTS: Body weight was significantly increased with HFD
      (vs. LFD) in males from week 14 (P = 0.0221) and in females from week 27 (P =
      0.0076). Fat mass and fat-free mass of all groups were significantly increased
      over time (all P < 0.0001), with a large variation observed in fat mass. Baseline
      fat mass, fat-free mass, and daily energy intake were significant predictors of
      future body weight for both sexes (P < 0.0001). Baseline fat mass was a
      significant predictor of future body fat (P < 0.0001). CONCLUSIONS: Both males
      and females have large variations in fat mass, and this variability increases
      over time, while that of fat-free mass remains relatively stable. Sex differences
      exist in HFD responses and multivariate predicting models of body weight.

PMID- 24942675
TI  - Effectiveness of MRI for the assessment of mesorectal fascia involvement in
      patients with rectal cancer: a systematic review and meta-analysis.
AB  - AIMS: Defining the most appropriate definition of mesorectal fascia involvement
      (MRF+) by reviewing literature and using new inclusion criteria to re-evaluate
      the effectiveness of MRI in the assessment of MRF+ for rectal cancer. METHODS:
      PubMed, Medline, Embase, and the Cochrane Library databases were electronically
      searched from 1999 to 2012. The bivariate random effects model was used to
      estimate the pooled outcomes of each subgroup. The definition of MRF+ in MRI and
      the influence of neoadjuvant chemoradiotherapy (neo-ChRT) were especially
      discussed. RESULTS: Fourteen studies involving 1,600 patients were included.
      Different definitions of MRF+ (<= 1, <= 2 and <= 5 mm) in MRI exhibited different
      pooled sensitivity (76, 79 and 92%), specificity (88, 66 and 48%) and diagnostic
      odds ratio (DOR) (22.4, 6.6 and 16.0). The definition of MRF+ at <= 1 mm showed
      the highest DOR. The specificity (88 vs. 93%, p = 0.026) and DOR (15.5 vs. 39.0,
      p = 0.001) were lower in patients who underwent neo-ChRT than those who did not
      while using <= 1 mm as the definition of MRF+. However, the sensitivity showed no
      significant difference (67 vs. 74%, p = 0.129). CONCLUSIONS: MRI is valuable for
      the assessment of MRF. The most appropriate definition of MRF+ in MRI is <= 1 mm.
      The effectiveness is higher in patients who did not undergo neo-ChRT.

PMID- 24942676
TI  - Sexual safety and sexual security among young Black women who have sex with women
      and men.
AB  - OBJECTIVE: To examine sexuality narratives of Black women who have sex with women
      and men and explore factors that influence their sexual safety and sexual
      security. DESIGN: Secondary qualitative content analysis. SETTING: We recruited
      young self-identified Black women from beauty salons and community-based
      organizations. PARTICIPANTS: Our sample included a subset of five sexually
      active, Black women age 19 to 25 who reported engaging in sexual relationships
      with women and men. Participants were selected from a larger parent study that
      included sexuality narratives from 25 women. METHODS: We analyzed interview
      transcripts in which participants described sexual relationships. We used
      constant comparative techniques and conventional content analysis methodology.
      RESULTS: We uncovered three themes illustrating influences on sexual safety and
      sexual security: institutional expectations, emotional connectedness, and sexual
      behaviors. CONCLUSIONS: From this analysis, we derive valuable insights into
      decision-making processes within sexual relationships from the perspectives of
      young Black women who have sex with women and men. Clinicians and investigators
      can use these findings to inform programs designed to improve the sexual health
      of this often invisible group of women. Nurses are uniquely positioned to support
      young women as they navigate societal institutions and emotional experiences that
      inform future sexual decisions and behaviors.

PMID- 24942677
TI  - Tailored immunity at mucosae.

PMID- 24942679
TI  - Maturation of the enteric mucosal innate immune system during the postnatal
      period.
AB  - The innate immune system instructs the host on microbial exposure and infection.
      This information is critical to mount a protective innate and adaptive host
      response to microbial challenge, but is also involved in homeostatic and adaptive
      processes that adjust the organism to meet environmental requirements. This is of
      particular importance for the neonatal host during the transition from the
      protected fetal life to the intense and dynamic postnatal interaction with
      commensal and pathogenic microorganisms. Here, we discuss both adaptive and
      developmental mechanisms of the mucosal innate immune system that prevent
      inappropriate stimulation and facilitate establishment of a stable homeostatic
      host-microbial interaction after birth.

PMID- 24942678
TI  - The mucus and mucins of the goblet cells and enterocytes provide the first
      defense line of the gastrointestinal tract and interact with the immune system.
AB  - The gastrointestinal tract is covered by mucus that has different properties in
      the stomach, small intestine, and colon. The large highly glycosylated gel
      forming mucins MUC2 and MUC5AC are the major components of the mucus in the
      intestine and stomach, respectively. In the small intestine, mucus limits the
      number of bacteria that can reach the epithelium and the Peyer's patches. In the
      large intestine, the inner mucus layer separates the commensal bacteria from the
      host epithelium. The outer colonic mucus layer is the natural habitat for the
      commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin
      but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and
      TFF3. The goblet cells have recently been shown to have a novel gate-keeping role
      for the presentation of oral antigens to the immune system. Goblet cells deliver
      small intestinal luminal material to the lamina propria dendritic cells of the
      tolerogenic CD103(+) type. In addition to the gel-forming mucins, the
      transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that
      can reach about a micrometer out from the brush border. The MUC17 mucin can
      shuttle from a surface to an intracellular vesicle localization, suggesting that
      enterocytes might control and report epithelial microbial challenge. There is
      communication not only from the epithelial cells to the immune system but also in
      the opposite direction. One example of this is IL10 that can affect and improve
      the properties of the inner colonic mucus layer. The mucus and epithelial cells
      of the gastrointestinal tract are the primary gate keepers and controllers of
      bacterial interactions with the host immune system, but our understanding of this
      relationship is still in its infancy.

PMID- 24942682
TI  - The role of the adaptive immune system in regulation of gut microbiota.
AB  - The gut nourishes rich bacterial communities that affect profoundly the functions
      of the immune system. The relationship between gut microbiota and the immune
      system is one of reciprocity. The microbiota contributes to nutrient processing
      and the development, maturation, and function of the immune system. Conversely,
      the immune system, particularly the adaptive immune system, plays a key role in
      shaping the repertoire of gut microbiota. The fitness of host immune system is
      reflected in the gut microbiota, and deficiencies in either innate or adaptive
      immunity impact on diversity and structures of bacterial communities in the gut.
      Here, we discuss the mechanisms that underlie this reciprocity and emphasize how
      the adaptive immune system via immunoglobulins (i.e. IgA) contributes to
      diversification and balance of gut microbiota required for immune homeostasis.

PMID- 24942681
TI  - B cells as a critical node in the microbiota-host immune system network.
AB  - Mutualism with our intestinal microbiota is a prerequisite for healthy existence.
      This requires physical separation of the majority of the microbiota from the host
      (by secreted antimicrobials, mucus, and the intestinal epithelium) and active
      immune control of the low numbers of microbes that overcome these physical and
      chemical barriers, even in healthy individuals. In this review, we address how B
      cell responses to members of the intestinal microbiota form a robust network with
      mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut
      associated lymphoid tissues to maintain host-microbiota mutualism.

PMID- 24942680
TI  - Anatomical localization of commensal bacteria in immune cell homeostasis and
      disease.
AB  - The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial
      commensal bacteria that are essential for promoting normal intestinal physiology.
      While the majority of commensal bacteria are found in the intestinal lumen, many
      species have also adapted to colonize different anatomical locations in the
      intestine, including the surface of intestinal epithelial cells (IECs) and the
      interior of gut-associated lymphoid tissues. These distinct tissue localization
      patterns permit unique interactions with the mammalian immune system and
      collectively influence intestinal immune cell homeostasis. Conversely,
      dysregulated localization of commensal bacteria can lead to inappropriate
      activation of the immune system and is associated with numerous chronic
      infectious, inflammatory, and metabolic diseases. Therefore, regulatory
      mechanisms that control proper anatomical containment of commensal bacteria are
      essential to maintain tissue homeostasis and limit pathology. In this review, we
      propose that commensal bacteria associated with the mammalian GI tract can be
      anatomically defined as (i) luminal, (ii) epithelial-associated, or (iii)
      lymphoid tissue-resident, and we discuss the role and regulation of these
      microbial populations in health and disease.

PMID- 24942684
TI  - Intestinal dendritic cells in the regulation of mucosal immunity.
AB  - The intestine presents a huge surface area to the outside environment, a property
      that is of critical importance for its key functions in nutrient digestion,
      absorption, and waste disposal. As such, the intestine is constantly exposed to
      dietary and microbial-derived foreign antigens, to which immune cells within the
      mucosa must suitably respond to maintain intestinal integrity, while also
      providing the ability to mount effective immune responses to potential pathogens.
      Dendritic cells (DCs) are sentinel immune cells that play a central role in the
      initiation and differentiation of adaptive immune responses. In the intestinal
      mucosa, DCs are located diffusely throughout the intestinal lamina propria,
      within gut-associated lymphoid tissues, including Peyer's patches and smaller
      lymphoid aggregates, as well as in intestinal-draining lymph nodes, including
      mesenteric lymph nodes. The recognition that dietary nutrients and microbial
      communities in the intestine influence both mucosal and systemic immune cell
      development and function as well as immune-mediated disease has led to an
      explosion of literature in mucosal immunology in recent years and a growing
      interest in the functionality of intestinal DCs. In the current review, we
      discuss recent findings from our group and others that have provided important
      insights regarding murine and human intestinal lamina propria DCs and highlighted
      marked developmental and functional heterogeneity within this compartment. A
      thorough understanding of the role these subsets play in the regulation of
      intestinal immune homeostasis and inflammation will help to define novel
      strategies for the treatment of intestinal pathologies and contribute to improved
      rational design of mucosal vaccines.

PMID- 24942683
TI  - Intestinal IgA production and its role in host-microbe interaction.
AB  - Complex and diverse communities of bacteria establish mutualistic and symbiotic
      relationships with the gut after birth. The intestinal immune system responds to
      bacterial colonization by acquiring a state of hypo-responsiveness against
      commensals and active readiness against pathogens. The resulting homeostatic
      balance involves a continuous dialog between the microbiota and lymphocytes with
      the intermediation of epithelial and dendritic cells. This dialog causes massive
      production of immunoglobulin A (IgA), a non-inflammatory antibody specialized in
      mucosal protection. Here, we discuss recent advances on the regulation of
      intestinal IgA responses and their role in host-microbe interaction.

PMID- 24942686
TI  - Dendritic cell-epithelial cell crosstalk in the gut.
AB  - Intestinal epithelial cells are fundamental to maintain barrier integrity and to
      participate in food degradation and absorption, but they can also decipher
      signals coming from the outside world and 'educate' the immune system
      accordingly. In particular, they interact with dendritic cells (DCs) and other
      intraepithelial immune cells to drive tolerogenic responses under steady state,
      but they can also release immune mediators to recruit inflammatory cells and to
      elicit immunity to infectious agents. When these interactions are deregulated,
      immune disorders can develop. In this review, we discuss some important features
      of epithelial cells and DCs and their fruitful interactions.

PMID- 24942685
TI  - Macrophages in intestinal homeostasis and inflammation.
AB  - The intestine contains the largest pool of macrophages in the body which are
      essential for maintaining mucosal homeostasis in the face of the microbiota and
      the constant need for epithelial renewal but are also important components of
      protective immunity and are involved in the pathology of inflammatory bowel
      disease (IBD). However, defining the biological roles of intestinal macrophages
      has been impeded by problems in defining the phenotype and origins of different
      populations of myeloid cells in the mucosa. Here, we discuss how multiple
      parameters can be used in combination to discriminate between functionally
      distinct myeloid cells and discuss the roles of macrophages during homeostasis
      and how these may change when inflammation ensues. We also discuss the evidence
      that intestinal macrophages do not fit the current paradigm that tissue-resident
      macrophages are derived from embryonic precursors that self-renew in situ, but
      require constant replenishment by blood monocytes. We describe our recent work
      demonstrating that classical monocytes constantly enter the intestinal mucosa and
      how the environment dictates their subsequent fate. We believe that understanding
      the factors that drive intestinal macrophage development in the steady state and
      how these may change in response to pathogens or inflammation could provide
      important insights into the treatment of IBD.

PMID- 24942687
TI  - Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense.
AB  - Respiratory infections and diseases are among the leading causes of death
      worldwide, and effective treatments probably require manipulating the
      inflammatory response to pathogenic microbes or allergens. Here, we review
      mechanisms controlling the production and functions of interleukin-17 (IL-17) and
      IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes
      (gammadelta T cells, natural killer cells, innate lymphoid cells) are the major
      source of IL-17 and IL-22 during acute infections, while CD4(+) T-helper 17
      (Th17) cells contribute to vaccine-induced immunity. The characterization of
      dendritic cell (DC) subsets has revealed their central roles in T-cell
      activation. CD11b(+) DCs stimulated with bacteria or fungi secrete IL-1beta and
      IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of
      viruses by plasmacytoid DCs inhibits IL-1beta and IL-23 release, increasing
      susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the
      lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants.
      Recent studies found that stimulation of macrophages and DCs with IL-17 also
      contributes to antibacterial immunity, while IL-22 promotes epithelial
      proliferation and repair following injury. Chronic diseases such as asthma and
      chronic obstructive pulmonary disease have been associated with IL-17 and IL-22
      responses directed against innocuous antigens. Future studies will evaluate the
      therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary
      inflammation.

PMID- 24942688
TI  - The role of type I interferons in intestinal infection, homeostasis, and
      inflammation.
AB  - Type I interferons are a widely expressed family of effector cytokines that
      promote innate antiviral and antibacterial immunity. Paradoxically, they can also
      suppress immune responses by driving production of anti-inflammatory cytokines,
      and dysregulation of these cytokines can contribute to host-mediated
      immunopathology and disease progression. Recent studies describe their anti
      inflammatory role in intestinal inflammation and the locus containing IFNAR, a
      heterodimeric receptor for the type I interferons has been identified as a
      susceptibility region for human inflammatory bowel disease. This review focuses
      on the role of type I IFNs in the intestine in health and disease and their
      emerging role as immune modulators. Clear understanding of type I IFN-mediated
      immune responses may provide avenues for fine-tuning existing IFN treatment for
      infection and intestinal inflammation.

PMID- 24942689
TI  - Immunity to intestinal pathogens: lessons learned from Salmonella.
AB  - Salmonella are a common source of food- or water-borne infection and cause a wide
      range of clinical disease in human and animal hosts. Salmonella are relatively
      easy to culture and manipulate in a laboratory setting, and the infection of
      laboratory animals induces robust innate and adaptive immune responses. Thus,
      immunologists have frequently turned to Salmonella infection models to expand
      understanding of host immunity to intestinal pathogens. In this review, I
      summarize current knowledge of innate and adaptive immunity to Salmonella and
      highlight features of this response that have emerged from recent studies. These
      include the heterogeneity of the antigen-specific T-cell response to intestinal
      infection, the prominence of microbial mechanisms to impede T- and B-cell
      responses, and the contribution of non-cognate pathways for elicitation of T-cell
      effector functions. Together, these different issues challenge an overly
      simplistic view of host-pathogen interaction during mucosal infection, but also
      allow deeper insight into the real-world dynamic of protective immunity to
      intestinal pathogens.

PMID- 24942693
TI  - Innate immunity in the lung regulates the development of asthma.
AB  - The lung, while functioning as a gas exchange organ, encounters a large array of
      environmental factors, including particulate matter, toxins, reactive oxygen
      species, chemicals, allergens, and infectious microbes. To rapidly respond to and
      counteract these elements, a number of innate immune mechanisms have evolved that
      can lead to lung inflammation and asthma, which is the focus of this review.
      These innate mechanisms include a role for two incompletely understood cell
      types, invariant natural killer T (iNKT) cells and innate lymphoid cells (ILCs),
      which together produce a wide range of cytokines, including interleukin-4 (IL-4),
      IL-5, IL-13, interferon-gamma, IL-17, and IL-22, independently of adaptive
      immunity and conventional antigens. The specific roles of iNKT cells and ILCs in
      immunity are still being defined, but both cell types appear to play important
      roles in the lungs, particularly in asthma. As we gain a better understanding of
      these innate cell types, we will acquire great insight into the mechanisms by
      which allergic and non-allergic asthma phenotypes develop.

PMID- 24942691
TI  - Microbiota activation and regulation of innate and adaptive immunity.
AB  - The human host has coevolved with the collective of bacteria species, termed
      microbiota, in a complex fashion that affects both innate and adaptive immunity.
      Differential regulation of regulatory T-cell and effector T-cell responses are a
      direct result of specific microbial species present within the gut, and this
      relationship is subject to dysregulation during inflammation and disease. The
      microbiota varies widely between individuals and has a profound effect on how one
      reacts to various environmental stimuli, particularly if a person is genetically
      predisposed to an immune-mediated inflammatory disorder such as inflammatory
      bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC).
      Approximately, half of all CD patients have elevated antibodies to CBir1, a
      microbiota flagellin common to mice and humans, demonstrating flagellins as
      immunodominant antigens in the intestines. This review focuses on the use of
      flagellins as probes to study microbiota-specific responses in the context of
      health and disease as well as probes of innate and adaptive responses employed by
      the host to deal with the overwhelming bacterial presence of the microbiota.

PMID- 24942690
TI  - Immunity to gastrointestinal nematodes: mechanisms and myths.
AB  - Immune responses to gastrointestinal nematodes have been studied extensively for
      over 80 years and intensively investigated over the last 30-40 years. The use of
      laboratory models has led to the discovery of new mechanisms of protective
      immunity and made major contributions to our fundamental understanding of both
      innate and adaptive responses. In addition to host protection, it is clear that
      immunoregulatory processes are common in infected individuals and resistance
      often operates alongside modulation of immunity. This review aims to discuss the
      recent discoveries in both host protection and immunoregulation against
      gastrointestinal nematodes, placing the data in context of the specific life
      cycles imposed by the different parasites studied and the future challenges of
      considering the mucosal/immune axis to encompass host, parasite, and microbiome
      in its widest sense.

PMID- 24942695
TI  - Case of advanced melanoma who died from meningitis carcinomatosa after
      carboplatin and paclitaxel with good response.

PMID- 24942694
TI  - Cellular and molecular mechanisms underlying NOD2 risk-associated polymorphisms
      in Crohn's disease.
AB  - The discovery that polymorphisms in the NOD2 (nucleotide-binding oligomerization
      domain containing 2) gene are associated with a greatly increased risk for the
      development of Crohn's disease has provided a means to achieve a deeper
      understanding of the dysregulation of mucosal immune responses to the commensal
      intestinal organisms that is thought to underlie this disease. NOD2 is a NOD-like
      receptor (NLR) family member that senses and responds to bacterial wall peptides;
      thus, the most widely held view of the relation of the NOD2 polymorphisms with
      Crohn's disease is that these polymorphisms lead to deficient immune responses to
      gut bacteria, and these, in turn, lead to quantitative or qualitative changes in
      the bacterial population in the gut lumen or lamina propria that cause
      inflammation at this site. Initially, this view was based mainly on the
      observation that defective NOD2 function can result in reduced alpha-defensin
      production by intestinal Paneth cells and that such impairment leads to loss of
      host defense against gut bacteria. In this review, we reconsider this possibility
      and marshal evidence that it is not in fact likely to be a prime element of
      Crohn's disease causation. More recently, evidence has been accumulating that the
      NOD2 dysfunction leads to Crohn's inflammation by inducing changes in the gut
      microbiome that influence immune effector or regulatory function. We review the
      strengths and weaknesses of this emerging hypothesis. Finally, we consider the
      possibility that NOD2 dysfunction can lead to inflammation because of a second
      and somewhat overlooked aspect of its function, that as an immunoregulator of
      innate immune responses. In particular, we review the body of evidence that NOD2
      stimulation activates a cross-tolerance response that downregulates and thus
      prevents excessive TLR responses that cause Crohn's inflammation.

PMID- 24942697
TI  - Careers in global neurology.

PMID- 24942696
TI  - Epicardial ablation as a bailout in electrical storm?
AB  - Electrical storm (ES) is one of the most challenging clinical scenarios facing
      electrophysiologists, and in certain settings emergency ablation should be
      performed. The majority of ES occurs in patients with structural heart disease,
      predominantly coronary heart disease and nonischemic heart disease like right
      ventricular arrhythmogenic dysplasia and previous myocarditis as well as other
      cardiomyopathies. Implantable cardioverter-defibrillators (ICDs) are the first
      line therapy in patients with ventricular tachycardia (VT) and structural heart
      disease. Recurrent VT episodes or ES are major problems in patients who receive
      an ICD after a spontaneous sustained VT. In addition, in patients with an ICD
      implanted for primary prevention of sudden cardiac death, 20 % will experience at
      least one VT episode within 3-5 years after ICD implantation. Catheter ablation
      has a high success rate in the acute setting in eliminating clinical VT. However,
      several factors make enodocardial catheter ablation of VT more difficult
      especially in advanced ischemic heart disease with heart failure and aneurysm.
      Frequently in nonischemic cardiomyopathies (NICM) there tends to be an epicardial
      and intramyocardial substrate where the critical VT zone can occasionally be
      epicardial or intramural in location. In some patients, an epicardial approach
      should be warranted first together with an endocardial approach or after failure
      of enodocardial ablation. Currently, the success rates of endocardial ablation in
      the acute setting are acceptable, but in the long term they are still not well
      defined. The purpose of this article is to highlight the importance of epicardial
      ablation as an alternative approach in controlling ES and to confirm the need for
      highly qualified centers to manage such challenging cases.

PMID- 24942692
TI  - IL-15: a central regulator of celiac disease immunopathology.
AB  - Interleukin-15 (IL-15) exerts many biological functions essential for the
      maintenance and function of multiple cell types. Although its expression is
      tightly regulated, IL-15 upregulation has been reported in many organ-specific
      autoimmune disorders. In celiac disease, an intestinal inflammatory disorder
      driven by gluten exposure, the upregulation of IL-15 expression in the intestinal
      mucosa has become a hallmark of the disease. Interestingly, because it is
      overexpressed both in the gut epithelium and in the lamina propria, IL-15 acts on
      distinct cell types and impacts distinct immune components and pathways to
      disrupt intestinal immune homeostasis. In this article, we review our current
      knowledge of the multifaceted roles of IL-15 with regard to the main
      immunological processes involved in the pathogenesis of celiac disease.

PMID- 24942698
TI  - Pulmonary hypertension in adult congenital heart disease.
AB  - OPINION STATEMENT: There is a growing patient population with adult congenital
      heart disease that needs specialized medical attention and careful long-term
      evaluation. Pulmonary arterial hypertension (PAH) associated with congenital
      heart disease (PAH-CHD) is a common late complication, and is associated with
      increased morbidity and mortality. There are no clear current guidelines for the
      treatment of PAH-CHD. There are few trials to date investigating PAH treatment
      specifically in this group of patients. However, the available data seems to
      demonstrate that with the advent of PAH-targeted therapies, the quality of life,
      exercise capacity, and outcomes in these patients is improving. In addition, PAH
      targeted therapies may be useful in select patients for a combined medical
      surgical approach to treatment. Here we discuss the epidemiology and
      pathophysiology of PAH-CHD, current therapies, and the data supporting their use,
      and how to evaluate feasibility of late surgical repair.

PMID- 24942699
TI  - Characterisation of circadian rhythms of various duckweeds.
AB  - The plant circadian clock controls various physiological phenomena that are
      important for adaptation to natural day-night cycles. Many components of the
      circadian clock have been identified in Arabidopsis thaliana, the model plant for
      molecular genetic studies. Recent studies revealed evolutionary conservation of
      clock components in green plants. Homologues of clock-related genes have been
      isolated from Lemna gibba and Lemna aequinoctialis, and it has been demonstrated
      that these homologues function in the clock system in a manner similar to their
      functioning in Arabidopsis. While clock components are widely conserved,
      circadian phenomena display diversity even within the Lemna genus. In order to
      survey the full extent of diversity in circadian rhythms among duckweed plants,
      we characterised the circadian rhythms of duckweed by employing a semi-transient
      bioluminescent reporter system. Using a particle bombardment method, circadian
      bioluminescent reporters were introduced into nine strains representing five
      duckweed species: Spirodela polyrhiza, Landoltia punctata, Lemna gibba, L.
      aequinoctialis and Wolffia columbiana. We then monitored luciferase (luc+)
      reporter activities driven by AtCCA1, ZmUBQ1 or CaMV35S promoters under
      entrainment and free-running conditions. Under entrainment, AtCCA1::luc+ showed
      similar diurnal rhythms in all strains. This suggests that the mechanism of
      biological timing under day-night cycles is conserved throughout the evolution of
      duckweeds. Under free-running conditions, we observed circadian rhythms of
      AtCCA1::luc+, ZmUBQ1::luc+ and CaMV35S::luc+. These circadian rhythms showed
      diversity in period length and sustainability, suggesting that circadian clock
      mechanisms are somewhat diversified among duckweeds.

PMID- 24942700
TI  - Accurate proteome-wide label-free quantification by delayed normalization and
      maximal peptide ratio extraction, termed MaxLFQ.
AB  - Protein quantification without isotopic labels has been a long-standing interest
      in the proteomics field. However, accurate and robust proteome-wide
      quantification with label-free approaches remains a challenge. We developed a new
      intensity determination and normalization procedure called MaxLFQ that is fully
      compatible with any peptide or protein separation prior to LC-MS analysis.
      Protein abundance profiles are assembled using the maximum possible information
      from MS signals, given that the presence of quantifiable peptides varies from
      sample to sample. For a benchmark dataset with two proteomes mixed at known
      ratios, we accurately detected the mixing ratio over the entire protein
      expression range, with greater precision for abundant proteins. The significance
      of individual label-free quantifications was obtained via a t test approach. For
      a second benchmark dataset, we accurately quantify fold changes over several
      orders of magnitude, a task that is challenging with label-based methods. MaxLFQ
      is a generic label-free quantification technology that is readily applicable to
      many biological questions; it is compatible with standard statistical analysis
      workflows, and it has been validated in many and diverse biological projects. Our
      algorithms can handle very large experiments of 500+ samples in a manageable
      computing time. It is implemented in the freely available MaxQuant computational
      proteomics platform and works completely seamlessly at the click of a button. 

PMID- 24942701
TI  - Meta-analysis of P300 waveform in panic disorder.
AB  - The P300 waveform has been inconsistently linked to the maladaptive information
      processing characterized in panic disorder (PD). The purpose of this study was to
      synthesize previous event-related potential (ERP) findings and determine whether
      patients with PD have significant abnormalities in the P300 wave compared to
      controls. We performed a systematic literature search for studies published
      between 1980 and 2013 that reported P300 measurements in patients with PD and
      controls. Effect size estimates were computed using the restricted maximum
      likelihood model. We identified 14 ERP studies that analyzed P300 amplitude (461
      PD and 355 controls), and 11 ERP studies that analyzed latency (320 PD and 282
      controls). Patients with PD had reduced P300 amplitudes compared to controls, but
      this difference was non significant at midline electrodes (n = 14, ES -0.16; z = 
      1.55, p = 0.122). However, P300 amplitude was significantly reduced when
      analyzing the Pz electrode independently (n = 7, ES -0.48, z = -3.92, p < 0.001).
      No significant differences between cases and controls in P300 latency were
      observed at the midline electrodes (n = 11, ES 0.11, z = 0.64, p = 0.524). This
      meta-analysis included non-peer reviewed literature and ERP stimuli with varying
      levels of emotional salience, which may have introduced bias into the analysis.
      There is no robust evidence that P300 latency alterations are present in patients
      with PD; however, there are indications of reduced amplitude at Pz relative to
      controls. Reductions in amplitude may be associated with reduced neural resources
      allocated to contextual updating, selective attention, and neural inhibition
      mechanisms.

PMID- 24942702
TI  - When a laser pen becomes a stick: remapping of space by tool-use observation in
      hemispatial neglect.
AB  - The role of active tool use in the remapping of space in hemispatial neglect
      patients has been extensively investigated. To date, however, there is no
      evidence that observing tool use can play a role in the remapping of space in
      hemispatial neglect patients. In this study, a patient with a severe hemispatial
      neglect in near but not far space and twelve healthy controls were asked to
      bisect near and far lines using a laser pen. The task was performed both before
      and immediately after sessions in which they merely observed the experimenter
      bisecting near and far lines with a stick. During the observation session,
      participants were either holding an identical stick or empty-handed. Results, in
      both the neglect patient and healthy controls, showed that observing the
      experimenter bisecting line while holding the same tool, produces a remapping of
      the far space into the near space. This result was particularly evident in the
      neglect patient where observing line-bisection task extended the spatial deficit
      from the near to the far space. Our results provide new empirical support to the
      idea that the space around us is not mapped in merely metrical terms, rather it
      seems to be deeply impacted by both action observation and execution.

PMID- 24942703
TI  - Anodal-tDCS applied during unilateral strength training increases strength and
      corticospinal excitability in the untrained homologous muscle.
AB  - Evidence suggests that the cross-transfer of strength following unilateral
      training may be modulated by increased corticospinal excitability of the
      ipsilateral primary motor cortex, due to cross-activation. Anodal-tDCS (a-tDCS)
      has been shown to acutely increase corticospinal excitability and motor
      performance, which may enhance this process. Therefore, we sought to examine
      changes in neural activation and strength of the untrained limb following the
      application of a-tDCS during a single unilateral strength training session. Ten
      participants underwent three conditions in a randomized, double-blinded crossover
      design: (1) strength training + a-tDCS, (2) strength training + sham-tDCS and (3)
      a-tDCS alone. a-tDCS was applied for 20 min at 2 mA over the right motor cortex.
      Unilateral strength training of the right wrist involved 4 * 6 wrist extensions
      at 70 % of maximum. Outcome measures included maximal voluntary strength,
      corticospinal excitability, short-interval intracortical inhibition, and cross
      activation. We observed a significant increase in strength of the untrained wrist
      (5.27 %), a decrease in short-interval intracortical inhibition (-13.49 %), and
      an increase in cross-activation (15.71 %) when strength training was performed
      with a-tDCS, but not following strength training with sham-tDCS, or tDCS alone.
      Corticospinal excitability of the untrained wrist increased significantly
      following both strength training with a-tDCS (17.29 %), and a-tDCS alone (15.15
      %), but not following strength training with sham-tDCS. These findings suggest
      that a single session of a-tDCS combined with unilateral strength training of the
      right limb increases maximal strength and cross-activation to the contralateral
      untrained limb.

PMID- 24942705
TI  - Localization of click trains and speech by cats: the negative level effect.
AB  - Although localization of sound in elevation is believed to depend on spectral
      cues, it has been shown with human listeners that the temporal features of sound
      can also greatly affect localization performance. Of particular interest is a
      phenomenon known as the negative level effect, which describes the deterioration
      of localization ability in elevation with increasing sound level and is observed
      only with impulsive or short-duration sound. The present study uses the gaze
      positions of domestic cats as measures of perceived locations of sound targets
      varying in azimuth and elevation. The effects of sound level on localization in
      terms of accuracy, precision, and response latency were tested for sound with
      different temporal features, such as a click train, a single click, a continuous
      sound that had the same frequency spectrum of the click train, and speech
      segments. In agreement with previous human studies, negative level effects were
      only observed with click-like stimuli and only in elevation. In fact,
      localization of speech sounds in elevation benefited significantly when the sound
      level increased. Our findings indicate that the temporal continuity of a sound
      can affect the frequency analysis performed by the auditory system, and the
      variation in the frequency spectrum contained in speech sound does not interfere
      much with the spectral coding for its location in elevation. 

PMID- 24942704
TI  - Is there a fundamental 300 Hz limit to pulse rate discrimination in cochlear
      implants?
AB  - Literature often refers to a 300 pps limit for cochlear implant (CI) electrical
      stimulation, above which pulse rate discrimination deteriorates or above which
      rate pitch is not perceived to increase. The present study investigated the
      effect on pulse rate difference limens (PRDLs) when using compound stimuli in
      which identical pulse trains were applied to multiple electrodes across the
      length of the electrode array and compared the results to those of single
      electrode stimuli. PRDLs of seven CI users were determined in two stimulus pulse
      phase conditions, one in which the phase delays between pulses on different
      electrodes were minimised (burst mode) and a second in which they were maximised
      (spread mode). PRDLs were measured at base rates of 100 to 600 pps in 100 pps
      intervals, using compound stimuli on one, two, five, nine and 18 electrodes. As
      smaller PRDLs were expected to reflect improved rate pitch perception, 18
      electrode spread mode stimuli were also included in a pitch ranking task. PRDLs
      improved markedly when multi-electrode compound stimuli were used, with average
      spread mode PRDLs across listeners between 6 and 8 % of the base rate in the
      whole range tested (i.e. up to 600 pps). PRDLs continued to improve as more
      electrodes were included, up to at least nine electrodes in the compound
      stimulus. Stimulus pulse phase had a significant influence on the results, with
      PRDLs being smaller in spread mode. Results indicate that pulse rate
      discrimination may be manipulated with stimulus parameter choice so that
      previously observed deterioration of PRDLs at 300 pps probably does not reflect a
      fundamental limitation to rate discrimination. However, rate pitch perception did
      not improve in the conditions that resulted in smaller PRDLs. This may indicate
      that listeners used cues other than pitch to perform the rate discrimination task
      or may reflect limitations in the electrically evoked neural excitation patterns
      presented to a rate pitch extraction mechanism.

PMID- 24942706
TI  - Preliminary characterization of voltage-activated whole-cell currents in
      developing human vestibular hair cells and calyx afferent terminals.
AB  - We present preliminary functional data from human vestibular hair cells and
      primary afferent calyx terminals during fetal development. Whole-cell recordings
      were obtained from hair cells or calyx terminals in semi-intact cristae prepared
      from human fetuses aged between 11 and 18 weeks gestation (WG). During early
      fetal development (11-14 WG), hair cells expressed whole-cell conductances that
      were qualitatively similar but quantitatively smaller than those observed
      previously in mature rodent type II hair cells. As development progressed (15-18
      WG), peak outward conductances increased in putative type II hair cells but did
      not reach amplitudes observed in adult human hair cells. Type I hair cells
      express a specific low-voltage activating conductance, G K,L. A similar current
      was first observed at 15 WG but remained relatively small, even at 18 WG. The
      presence of a "collapsing" tail current indicates a maturing type I hair cell
      phenotype and suggests the presence of a surrounding calyx afferent terminal. We
      were also able to record from calyx afferent terminals in 15-18 WG cristae. In
      voltage clamp, these terminals exhibited fast inactivating inward as well as
      slower outward conductances, and in current clamp, discharged a single action
      potential during depolarizing steps. Together, these data suggest the major
      functional characteristics of type I and type II hair cells and calyx terminals
      are present by 18 WG. Our study also describes a new preparation for the
      functional investigation of key events that occur during maturation of human
      vestibular organs.

PMID- 24942707
TI  - Comorbid mental disorders in children and adolescents with attention
      deficit/hyperactivity disorder in a large nationwide study.
AB  - The present study aimed at identifying the full range of mental disorders
      comorbid to attention-deficit/hyperactivity disorder (ADHD) in children and
      adolescents (age 4-17) diagnosed in Danish psychiatric hospitals between 1995 and
      2010. A total of 14,825 patients were included in the study and comorbid
      disorders diagnosed concurrent with ADHD were identified. Associations of
      comorbid disorders with sex, age, and other mental disorders were investigated by
      logistic regression analysis. In the total sample, 52.0 % of the patients had at
      least one psychiatric disorder comorbid to ADHD and 26.2 % had two or more
      comorbid disorders. The most frequent comorbid disorders were disorders of
      conduct (16.5 %), specific developmental disorders of language, learning and
      motor development (15.4 %), autism spectrum disorders (12.4 %), and intellectual
      disability (7.9 %). Male sex was generally associated with an increased risk for
      neuropsychiatric disorders while female sex was associated more frequently with
      internalizing disorders. The analysis of associations between the various
      comorbid disorders identified several clusters highlighting the differential
      developmental trajectories seen in patients with ADHD. The study provides
      evidence that comorbidity with mental disorders is developmentally sensitive.
      Furthermore, the study shows that particular attention should be given to
      patients with neurodevelopmental disorders such as autism and intellectual
      disability in future longitudinal analyses. These disorders are very frequent in
      patients with ADHD, and the affected patients might follow a different course
      than patients without these disorders. 

PMID- 24942708
TI  - Validation of point-of-care testing for coeliac disease in children in a tertiary
      hospital in north India.
AB  - OBJECTIVE: Some of the conventional serological tests for coeliac disease (CD)
      are expensive, time-consuming and not readily available in developing countries,
      leading to a delay in diagnosis. Recently, point-of-care tests (POCT) have been
      manufactured and tested in Europe but have not been validated in our setting. We
      therefore aimed to study the diagnostic accuracy of the POCT 'Biocard' test in
      diagnosing CD in Indian children. DESIGN: Cross-sectional study. SETTING:
      Tertiary care centre in north India. PATIENTS: Children, aged 2-18 years, with
      chronic diarrhoea, short stature or refractory anaemia underwent serological
      testing for CD with antiendomysial antibodies (AEA), antitissue transglutaminase
      (tTG) antibodies and Biocard test followed by duodenal biopsy irrespective of
      serological results. CD was diagnosed with positive AEA and duodenal biopsy
      showing >grade 2 changes using modified Marsh criteria. Those who were both AEA
      negative and had normal histology were considered CD negative. RESULTS: Of 319
      children who underwent the serological testing, 170 agreed for biopsy. Of these,
      110 were diagnosed with CD and 30 were found to be CD negative. Remaining 30 had
      discordant AEA and histology results and were not included in analysis. Biocard
      test agreed with 92/110 positive and 27/30 negative diagnoses based on reference
      tests (83.6% sensitivity and 90% specificity). tTG was found to be 93.8%
      sensitive and 96.4% specific. CONCLUSIONS: We successfully validated the POCT for
      CD in our setting. It could be used to increase case detection rates in
      developing countries with a large undiagnosed CD burden.

PMID- 24942710
TI  - Changing motivations during migration: linking movement speed to reproductive
      status in a migratory large mammal.
AB  - A challenge in animal ecology is to link animal movement to demography. In
      general, reproducing and non-reproducing animals may show different movement
      patterns. Dramatic changes in reproductive status, such as the loss of an
      offspring during the course of migration, might also affect movement. Studies
      linking movement speed to reproductive status require individual monitoring of
      life-history events and hence are rare. Here, we link movement data from 98 GPS
      collared female moose (Alces alces) to field observations of reproductive status
      and calf survival. We show that reproductive females move more quickly during
      migration than non-reproductive females. Further, the loss of a calf over the
      course of migration triggered a decrease in speed of the female. This is in
      contrast to what might be expected for females no longer constrained by an
      accompanying offspring. The observed patterns demonstrate that females of
      different reproductive status may have distinct movement patterns, and that the
      underlying motivation to move may be altered by a change in reproductive status
      during migration. 

PMID- 24942709
TI  - Vitamin D and nifedipine in the treatment of Chinese patients with grades I-II
      essential hypertension: a randomized placebo-controlled trial.
AB  - OBJECTIVES: Low vitamin D status has been shown to be associated with
      hypertension. We planned to research the effect of vitamin D and nifedipine in
      the treatment of patients with essential hypertension. METHODS: Patients with
      grades I-II essential hypertension were enrolled in this single-center, double
      blind, placebo-controlled trial in Beijing. All patients received a conventional
      antihypertensive drug (nifedipine, 30 mg/d). One hundred and twenty-six patients
      were randomly assigned to receive vitamin D (n=63, 2000 IU/d) or a placebo (n=63)
      as an add-on to nifedipine, by the method of permutated block randomization.
      Ambulatory blood pressure monitoring was performed at baseline (month 0), at
      month 3 and at month 6. RESULTS: In vitamin D supplementation group, there was a
      significant increase in mean 25-hydroxyvitamin D levels from baseline (19.4 +/-
      11.6 ng/ml) to 6 months (34.1 +/- 12.2 ng/ml; p<0.001). At 6 months, the primary
      end points, a difference in the fall of 24-h mean blood pressure, between the
      groups was -6.2 mmHg (95% CI -11.2; -1.1) for systolic blood pressure (p<0.001)
      and -4.2 mmHg (95% CI -8.8; -0.3) for diastolic blood pressure (p<0.001) under
      intention to treat analysis. In patients with vitamin D <30 ng/ml at baseline
      (n=113), 24-h mean blood pressure decreased by 7.1/5.7 mmHg (p<0.001). Safety and
      tolerability were similar among the two groups. CONCLUSIONS: Vitamin D
      supplementation can reduce blood pressure in patients with hypertension, it can
      be an adjuvant therapy for patients with grades I-II essential hypertension.
      CLINICAL TRIAL REGISTRATION: This study was registered in the Chinese Clinical
      Trial Registry, it is available in Website: http://www.chictr.org/cn/;
      REGISTRATION NUMBER: ChiCTR-ONC-13003840.

PMID- 24942711
TI  - Cutaneous mucinosis in a strain of brown-egg laying chickens.
AB  - Cutaneous mucinosis is a cutaneous disorder described in humans, dogs, and rarely
      cats but never reported in birds. Twenty-six brown egg-laying chickens between
      ages 43 and 46 weeks had a history of feather loss, scaly, dry skin, weight loss,
      and decreased egg production. Microscopic findings in the skin included
      fragmentation of collagen bundles and interstitial, periadnexal, and perivascular
      dermal accumulation of wispy, mildly basophilic material that was also
      occasionally observed within the follicular epithelium. A moderate
      lymphoplasmacytic and heterophilic perivascular dermatitis was also observed. The
      wispy to granular material was diffusely Alcian blue positive and periodic acid
      Schiff negative (consistent with mucin), suggesting a diagnosis of primary or
      secondary cutaneous mucinosis. The cause of this condition could not be
      determined. 

PMID- 24942712
TI  - IV. Increased kidney donation rates in the Scottish NHS: a historical problem
      being successfully addressed.

PMID- 24942714
TI  - Beta-blocking agents during electroconvulsive therapy: a review.
AB  - Electroconvulsive therapy (ECT) is associated with at least transient episodes of
      hypertension and tachycardia. Beta-blocking agents may be indicated to prevent
      cardiovascular complications and may shorten seizure duration. This review
      evaluates studies that used beta-blocking agents during ECT to determine which
      agent has the most favourable outcomes on cardiovascular variables and seizure
      duration. A Medline database search was made using the combined keywords
      'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was
      restricted to double-blind randomized controlled trials and yielded 29 original
      studies. With the use of esmolol, significant attenuating effects were found on
      cardiovascular parameters in the first 5 min after stimulation; its shortening
      effects on seizure duration may be dose-related. With the use of labetalol,
      findings on cardiovascular effects were inconsistent during the first minutes
      after stimulation but were significant after 5 min and thereafter; seizure
      duration was scarcely studied. Landiolol attenuates heart rate but with
      inconsistent findings regarding arterial pressure (AP); seizure duration was
      mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular
      response, although seizure duration may be affected with higher dosages.
      Landiolol can be considered a suitable alternative, but effects on AP need
      further investigation. Labetalol has been studied to a lesser extent and may have
      prolonged cardiovascular effects. The included studies varied in design,
      methodology, and the amount of exact data provided in the publications. Further
      study of beta-blocking agents in ECT is clearly necessary. 

PMID- 24942713
TI  - Dexamethasone and haemorrhage risk in paediatric tonsillectomy: a systematic
      review and meta-analysis.
AB  - Summary In children undergoing tonsillectomy, dexamethasone is recommended to
      reduce the risk of postoperative nausea and vomiting while non-steroidal anti
      inflammatory drugs (NSAIDs) are used for pain relief. We aimed to determine
      whether children who receive dexamethasone or dexamethasone with NSAID are more
      likely to experience haemorrhage post-tonsillectomy. Randomized and non
      randomized studies in which children undergoing tonsillectomy received
      dexamethasone or dexamethasone and NSAID were sought within bibliographic
      databases and selected tertiary sources. The risk of bias assessment and
      evaluation of haemorrhage rate data collection and reporting were assessed using
      the Cochrane Risk of Bias Tool and McHarm tool. Synthesis methods comprised
      pooled estimate of the effect of dexamethasone on the risk of haemorrhage rate
      using the Peto odds ratio (OR) method. The pooled estimate for haemorrhage rate
      in children who received dexamethasone was 6.2%, OR 1.41 (95% confidence interval
      0.89-2.25, P=0.15). There was risk of bias and inconsistent data collection and
      reporting rates of haemorrhage in many of the included studies. Clinical
      heterogeneity was observed between studies. The pooled analysis did not
      demonstrate a statistically significant increase in the risk of post
      tonsillectomy haemorrhage with dexamethasone with/without NSAID use in children.
      However, the majority of the included studies were not designed to investigate
      this endpoint, and thus large studies which are specifically designed to collect
      data on haemorrhage rate are needed. 

PMID- 24942716
TI  - Ultrasound standard for lumbar plexus block.

PMID- 24942715
TI  - Laparoscopic surgery in a morbidly obese, high-risk cardiac patient: the benefits
      of deep neuromuscular block and sugammadex.

PMID- 24942717
TI  - Translaryngeal open ventilation for percutaneous endoscopic tracheostomy.

PMID- 24942718
TI  - In the new era of ultrasound guidance: is pneumothorax from supraclavicular block
      a rare complication of the past?

PMID- 24942719
TI  - Academic anaesthesia: the trend in UK publishing in the BJA between 2004 and
      2013.

PMID- 24942720
TI  - Thrombus in left ventricle discovered by transoesophageal echocardiography (TOE)
      in a patient with acute abdomen: how TOE can be crucial for decision-making in
      non-cardiac surgery.

PMID- 24942721
TI  - Counter statement to open letter to the Executive Director of the European
      Medicines Agency concerning the licensing of hydroxyethyl starch solutions for
      fluid resuscitation.

PMID- 24942722
TI  - Evaluation of acoustic respiration rate monitoring after extubation in intensive
      care unit patients.

PMID- 24942723
TI  - Long-term activation of polymorph cannabinoid receptors does not affect receptor
      gene transcription.

PMID- 24942731
TI  - Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling.
AB  - The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer
      cells and human tumors. Because a modulation of GPR55 activity by cannabinoids
      has been suggested, we analyzed whether this receptor participates in cannabinoid
      effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in
      cancer cells, that these structures possess unique signaling properties, and that
      modulation of these heteromers can modify the antitumoral activity of
      cannabinoids in vivo. These findings unveil the existence of previously unknown
      signaling platforms that help explain the complex behavior of cannabinoids and
      may constitute new targets for therapeutic intervention in oncology. 

PMID- 24942732
TI  - Soluble, prefibrillar alpha-synuclein oligomers promote complex I-dependent, Ca2+
      induced mitochondrial dysfunction.
AB  - alpha-Synuclein (alphaSyn) aggregation and mitochondrial dysfunction both
      contribute to the pathogenesis of Parkinson disease (PD). Although recent studies
      have suggested that mitochondrial association of alphaSyn may disrupt
      mitochondrial function, it is unclear what aggregation state of alphaSyn is most
      damaging to mitochondria and what conditions promote or inhibit the effect of
      toxic alphaSyn species. Because the neuronal populations most vulnerable in PD
      are characterized by large cytosolic Ca(2+) oscillations that burden
      mitochondria, we examined mitochondrial Ca(2+) stress in an in vitro system
      comprising isolated mitochondria and purified recombinant human alphaSyn in
      various aggregation states. Using fluorimetry to simultaneously measure four
      mitochondrial parameters, we observed that soluble, prefibrillar alphaSyn
      oligomers, but not monomeric or fibrillar alphaSyn, decreased the retention time
      of exogenously added Ca(2+), promoted Ca(2+)-induced mitochondrial swelling and
      depolarization, and accelerated cytochrome c release. Inhibition of the
      permeability transition pore rescued these alphaSyn-induced changes in
      mitochondrial parameters. Interestingly, the mitotoxic effects of alphaSyn were
      specifically dependent upon both electron flow through complex I and
      mitochondrial uptake of exogenous Ca(2+). Our results suggest that soluble
      prefibrillar alphaSyn oligomers recapitulate several mitochondrial phenotypes
      previously observed in animal and cell models of PD: complex I dysfunction,
      altered membrane potential, disrupted Ca(2+) homeostasis, and enhanced cytochrome
      c release. These data reveal how the association of oligomeric alphaSyn with
      mitochondria can be detrimental to the function of cells with high Ca(2+)
      handling requirements. 

PMID- 24942733
TI  - Arsenite stress down-regulates phosphorylation and 14-3-3 binding of leucine-rich
      repeat kinase 2 (LRRK2), promoting self-association and cellular redistribution.
AB  - Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are a common
      genetic cause of Parkinson disease, but the mechanisms whereby LRRK2 is regulated
      are unknown. Phosphorylation of LRRK2 at Ser(910)/Ser(935) mediates interaction
      with 14-3-3. Pharmacological inhibition of its kinase activity abolishes
      Ser(910)/Ser(935) phosphorylation and 14-3-3 binding, and this effect is also
      mimicked by pathogenic mutations. However, physiological situations where
      dephosphorylation occurs have not been defined. Here, we show that arsenite or
      H2O2-induced stresses promote loss of Ser(910)/Ser(935) phosphorylation, which is
      reversed by phosphatase inhibition. Arsenite-induced dephosphorylation is
      accompanied by loss of 14-3-3 binding and is observed in wild type, G2019S, and
      kinase-dead D2017A LRRK2. Arsenite stress stimulates LRRK2 self-association and
      association with protein phosphatase 1alpha, decreases kinase activity and GTP
      binding in vitro, and induces translocation of LRRK2 to centrosomes. Our data
      indicate that signaling events induced by arsenite and oxidative stress may
      regulate LRRK2 function. 

PMID- 24942734
TI  - A hyaluronan receptor for endocytosis (HARE) link domain N-glycan is required for
      extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB)
      signaling in response to the uptake of hyaluronan but not heparin, dermatan
      sulfate, or acetylated low density lipoprotein (LDL).
AB  - The human hyaluronan (HA) receptor for endocytosis (HARE; the 190-kDa C terminus
      of Stab2) is a major clearance receptor for multiple circulating ligands
      including HA, heparin (Hep), acetylated LDL (AcLDL), dermatan sulfate (DS),
      apoptotic debris, and chondroitin sulfate types A, C, D, and E. We previously
      found that HARE contains an N-glycan in the HA binding Link domain (at
      Asn(2280)), and cells expressing membrane-bound HARE(N2280A) bind and endocytose
      HA normally (Harris, E. N., Parry, S., Sutton-Smith, M., Pandey, M. S., Panico,
      M., Morris, H. R., Haslam, S. M., Dell, A., and Weigel, P. H. (2010) Glycobiology
      20, 991-1001). Also, NF-kappaB-mediated signaling is activated by HARE-mediated
      endocytosis of HA, Hep, AcLDL, or DS but not by chondroitin sulfates (Pandey, M.
      S., and Weigel, P. H. (2014) J. Biol. Chem. 289, 1756-1767). Here we investigated
      the role of Link N-glycans in ligand uptake and NF-kappaB and ERK1/2 signaling.
      HA.HARE-mediated ERK1/2 activation was HA size- dependent, as found for NF-kappaB
      activation. HARE(N2280A) cells internalized HA, Hep, AcLDL, and DS normally. No
      ERK1/2 activation occurred during HA endocytosis by HARE(N2280A) cells, but
      activation did occur with Hep. Dual-luciferase recorder assays showed that NF
      kappaB-mediated gene expression occurred normally in HARE(N2280A) cells
      endocytosing Hep, AcLDL, or DS but did not occur with HA. Activation of NF-kappaB
      by endogenous degradation of IkappaB-alpha was observed for HARE(N2280A) cells
      endocytosing Hep, AcLDL, or DS but not HA. We conclude that a Link domain complex
      N-glycan is required specifically for HARE.HA-mediated activation of ERK1/2 and
      NF-kappaB-mediated gene expression and that this initial activation mechanism is
      different from and independent of the initial mechanisms for HARE-mediated
      signaling in response to Hep, AcLDL, or DS uptake. 

PMID- 24942735
TI  - Molecular characterization of quinate and shikimate metabolism in Populus
      trichocarpa.
AB  - The shikimate pathway leads to the biosynthesis of aromatic amino acids essential
      for protein biosynthesis and the production of a wide array of plant secondary
      metabolites. Among them, quinate is an astringent feeding deterrent that can be
      formed in a single step reaction from 3-dehydroquinate catalyzed by quinate
      dehydrogenase (QDH). 3-Dehydroquinate is also the substrate for shikimate
      biosynthesis through the sequential actions of dehydroquinate dehydratase (DQD)
      and shikimate dehydrogenase (SDH) contained in a single protein in plants. The
      reaction mechanism of QDH resembles that of SDH. The poplar genome encodes five
      DQD/SDH-like genes (Poptr1 to Poptr5), which have diverged into two distinct
      groups based on sequence analysis and protein structure prediction. In vitro
      biochemical assays proved that Poptr1 and -5 are true DQD/SDHs, whereas Poptr2
      and -3 instead have QDH activity with only residual DQD/SDH activity. Poplar
      DQD/SDHs have distinct expression profiles suggesting separate roles in protein
      and lignin biosynthesis. Also, the QDH genes are differentially expressed. In
      summary, quinate (secondary metabolism) and shikimate (primary metabolism)
      metabolic activities are encoded by distinct members of the same gene family,
      each having different physiological functions. 

PMID- 24942736
TI  - A cleavage-potentiated fragment of tear lacritin is bactericidal.
AB  - Antimicrobial peptides are important as the first line of innate defense, through
      their tendency to disrupt bacterial membranes or intracellular pathways and
      potentially as the next generation of antibiotics. How they protect wet epithelia
      is not entirely clear, with most individually inactive under physiological
      conditions and many preferentially targeting Gram-positive bacteria. Tears
      covering the surface of the eye are bactericidal for Gram-positive and -negative
      bacteria. Here we narrow much of the bactericidal activity to a latent C-terminal
      fragment in the prosecretory mitogen lacritin and report that the mechanism
      combines membrane permeabilization with rapid metabolic changes, including
      reduced levels of dephosphocoenzyme A, spermidine, putrescine, and
      phosphatidylethanolamines and elevated alanine, leucine, phenylalanine,
      tryptophan, proline, glycine, lysine, serine, glutamate, cadaverine, and
      pyrophosphate. Thus, death by metabolic stress parallels cellular attempts to
      survive. Cleavage-dependent appearance of the C-terminal cationic amphipathic
      alpha-helix is inducible within hours by Staphylococcus epidermidis and slowly by
      another mechanism, in a chymotrypsin- or leupeptin protease-inhibitable manner.
      Although bactericidal at low micromolar levels, within a biphasic 1-10 nM dose
      optimum, the same domain is mitogenic and cytoprotective for epithelia via a
      syndecan-1 targeting mechanism dependent on heparanase. Thus, the C terminus of
      lacritin is multifunctional by dose and proteolytic processing and appears to
      play a key role in the innate protection of the eye, with wider potential benefit
      elsewhere as lacritin flows from exocrine secretory cells.

PMID- 24942737
TI  - Structure-function studies with the unique hexameric form II ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) from Rhodopseudomonas palustris.
AB  - The first x-ray crystal structure has been solved for an activated transition
      state analog-bound form II ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco). This enzyme, from Rhodopseudomonas palustris, assembles as a unique
      hexamer with three pairs of catalytic large subunit homodimers around a central 3
      fold symmetry axis. This oligomer arrangement is unique among all known Rubisco
      structures, including the form II homolog from Rhodospirillum rubrum. The
      presence of a transition-state analog in the active site locked the activated
      enzyme in a "closed" conformation and revealed the positions of critical active
      site residues during catalysis. Functional roles of two form II-specific residues
      (Ile(165) and Met(331)) near the active site were examined via site-directed
      mutagenesis. Substitutions at these residues affect function but not the ability
      of the enzyme to assemble. Random mutagenesis and suppressor selection in a
      Rubisco deletion strain of Rhodobacter capsulatus identified a residue in the
      amino terminus of one subunit (Ala(47)) that compensated for a negative change
      near the active site of a neighboring subunit. In addition, substitution of the
      native carboxyl-terminal sequence with the last few dissimilar residues from the
      related R. rubrum homolog increased the enzyme's kcat for carboxylation. However,
      replacement of a longer carboxyl-terminal sequence with termini from either a
      form III or a form I enzyme, which varied both in length and sequence, resulted
      in complete loss of function. From these studies, it is evident that a number of
      subtle interactions near the active site and the carboxyl terminus account for
      functional differences between the different forms of Rubiscos found in nature. 

PMID- 24942738
TI  - Stress conditions promote yeast Gap1 permease ubiquitylation and down-regulation
      via the arrestin-like Bul and Aly proteins.
AB  - Gap1, the yeast general amino acid permease, is a convenient model for studying
      how the intracellular traffic of membrane transporters is regulated. Present at
      the plasma membrane under poor nitrogen supply conditions, it undergoes
      ubiquitylation, endocytosis, and degradation upon activation of the TORC1 kinase
      complex in response to an increase in internal amino acids. This down-regulation
      is stimulated by TORC1-dependent phosphoinhibition of the Npr1 kinase, resulting
      in activation by dephosphorylation of the arrestin-like Bul1 and Bul2 adaptors
      recruiting the Rsp5 ubiquitin ligase to Gap1. We report here that Gap1 is also
      down-regulated when cells are treated with the TORC1 inhibitor rapamycin or
      subjected to various stresses and that a lack of the Tco89 subunit of TORC1
      causes constitutive Gap1 down-regulation. Both the Bul1 and Bul2 and the Aly1 and
      Aly2 arrestin-like adaptors of Rsp5 promote this down-regulation without
      undergoing dephosphorylation. Furthermore, they act via the C-terminal regions of
      Gap1 not involved in ubiquitylation in response to internal amino acids, whereas
      a Gap1 mutant altered in the N-terminal tail and resistant to ubiquitylation by
      internal amino acids is efficiently down-regulated under stress via the Bul and
      Aly adaptors. Although the Bul proteins mediate Gap1 ubiquitylation of two
      possible lysines, Lys-9 and Lys-16, the Aly proteins promote ubiquitylation of
      the Lys-16 residue only. This stress-induced pathway of Gap1 down-regulation
      targets other permeases as well, and it likely allows cells facing adverse
      conditions to retrieve amino acids from permease degradation. 

PMID- 24942739
TI  - The nuclear localization of gamma-tubulin is regulated by SadB-mediated
      phosphorylation.
AB  - gamma-Tubulin is an important cell division regulator that arranges microtubule
      assembly and mitotic spindle formation. Cytosolic gamma-tubulin nucleates alpha-
      and beta-tubulin in a growing microtubule by forming the ring-shaped protein
      complex gammaTuRC. Nuclear gamma-tubulin also regulates S-phase progression by
      moderating the activities of E2 promoter-binding factors. The mechanism that
      regulates localization of gamma-tubulin is currently unknown. Here, we
      demonstrate that the human Ser/Thr kinase SadB short localizes to chromatin and
      centrosomes. We found that SadB-mediated phosphorylation of gamma-tubulin on
      Ser(385) formed chromatin-associated gamma-tubulin complexes that moderate gene
      expression. In this way, the C-terminal region of gamma-tubulin regulates S-phase
      progression. In addition, chromatin levels of gamma-tubulin were decreased by the
      reduction of SadB levels or expression of a non-phosphorylatable Ala(385)-gamma
      tubulin but were enhanced by expression of SadB, wild-type gamma-tubulin, or a
      phosphomimetic Asp(385)-gamma-tubulin mutant. Our results demonstrate that SadB
      kinases regulate the cellular localization of gamma-tubulin and thereby control S
      phase progression. 

PMID- 24942740
TI  - Effects of zinc on particulate methane monooxygenase activity and structure.
AB  - Particulate methane monooxygenase (pMMO) is a membrane-bound metalloenzyme that
      oxidizes methane to methanol in methanotrophic bacteria. Zinc is a known
      inhibitor of pMMO, but the details of zinc binding and the mechanism of
      inhibition are not understood. Metal binding and activity assays on membrane
      bound pMMO from Methylococcus capsulatus (Bath) reveal that zinc inhibits pMMO at
      two sites that are distinct from the copper active site. The 2.6 A resolution
      crystal structure of Methylocystis species strain Rockwell pMMO reveals two
      previously undetected bound lipids, and metal soaking experiments identify likely
      locations for the two zinc inhibition sites. The first is the crystallographic
      zinc site in the pmoC subunit, and zinc binding here leads to the ordering of 10
      previously unobserved residues. A second zinc site is present on the cytoplasmic
      side of the pmoC subunit. Parallels between these results and zinc inhibition
      studies of several respiratory complexes suggest that zinc might inhibit proton
      transfer in pMMO. 

PMID- 24942741
TI  - Hydrogen sulfide represses androgen receptor transactivation by targeting at the
      second zinc finger module.
AB  - Androgen receptor (AR) signaling is indispensable for the development of prostate
      cancer from the initial androgen-dependent state to a later aggressive androgen
      resistant state. This study examined the role of hydrogen sulfide (H(2)S), a
      novel gasotransmitter, in the regulation of AR signaling as well as its mediation
      in androgen-independent cell growth in prostate cancer cells. Here we found that
      H(2)S inhibits cell proliferation of both androgen-dependent (LNCaP) and
      antiandrogen-resistant prostate cancer cells (LNCaP-B), with more significance on
      the latter, which was established by long term treatment of parental LNCaP cells
      with bicalutamide. The expression of cystathionine gamma-lyase (CSE), a major
      H(2)S producing enzyme in prostate tissue, was reduced in both human prostate
      cancer tissues and LNCaP-B cells. LNCaP-B cells were resistant to bicalutamide
      induced cell growth inhibition, and CSE overexpression could rebuild the
      sensitivity of LNCaP-B cells to bicalutamide. H(2)S significantly repressed the
      expression of prostate-specific antigen (PSA) and TMPRSS2, two AR-targeted genes.
      In addition, H(2)S inhibited AR binding with PSA promoter and androgen-responsive
      element (ARE) luciferase activity. We further found that AR is post
      translationally modified by H(2)S through S-sulfhydration. Mutation of cysteine
      611 and cysteine 614 in the second zinc finger module of AR-DNA binding domain
      diminished the effects of H(2)S on AR S-sulfhydration and AR dimerization. These
      data suggest that reduced CSE/H2S signaling contributes to antiandrogen-resistant
      status, and sufficient level of H(2)S is able to inhibit AR transactivation and
      treat castration-resistant prostate cancer.

PMID- 24942742
TI  - Maturation of Rhizobium leguminosarum hydrogenase in the presence of oxygen
      requires the interaction of the chaperone HypC and the scaffolding protein HupK.
AB  - [NiFe] hydrogenases are key enzymes for the energy and redox metabolisms of
      different microorganisms. Synthesis of these metalloenzymes involves a complex
      series of biochemical reactions catalyzed by a plethora of accessory proteins,
      many of them required to synthesize and insert the unique NiFe(CN)2CO cofactor.
      HypC is an accessory protein conserved in all [NiFe] hydrogenase systems and
      involved in the synthesis and transfer of the Fe(CN)2CO cofactor precursor.
      Hydrogenase accessory proteins from bacteria-synthesizing hydrogenase in the
      presence of oxygen include HupK, a scaffolding protein with a moderate sequence
      similarity to the hydrogenase large subunit and proposed to participate as an
      intermediate chaperone in the synthesis of the NiFe cofactor. The endosymbiotic
      bacterium Rhizobium leguminosarum contains a single hydrogenase system that can
      be expressed under two different physiological conditions: free-living
      microaerobic cells (~ 12 MUm O2) and bacteroids from legume nodules (~ 10-100 nm
      O2). We have used bioinformatic tools to model HupK structure and interaction of
      this protein with HypC. Site-directed mutagenesis at positions predicted as
      critical by the structural analysis have allowed the identification of HupK and
      HypC residues relevant for the maturation of hydrogenase. Mutant proteins altered
      in some of these residues show a different phenotype depending on the
      physiological condition tested. Modeling of HypC also predicts the existence of a
      stable HypC dimer whose presence was also demonstrated by immunoblot analysis.
      This study widens our understanding on the mechanisms for metalloenzyme
      biosynthesis in the presence of oxygen.

PMID- 24942743
TI  - A structural and biochemical model of processive chitin synthesis.
AB  - Chitin synthases (CHS) produce chitin, an essential component of the fungal cell
      wall. The molecular mechanism of processive chitin synthesis is not understood,
      limiting the discovery of new inhibitors of this enzyme class. We identified the
      bacterial glycosyltransferase NodC as an appropriate model system to study the
      general structure and reaction mechanism of CHS. A high throughput screening
      compatible novel assay demonstrates that a known inhibitor of fungal CHS also
      inhibit NodC. A structural model of NodC, on the basis of the recently published
      BcsA cellulose synthase structure, enabled probing of the catalytic mechanism by
      mutagenesis, demonstrating the essential roles of the DD and QXXRW catalytic
      motifs. The NodC membrane topology was mapped, validating the structural model.
      Together, these approaches give insight into the CHS structure and mechanism and
      provide a platform for the discovery of inhibitors for this antifungal target. 

PMID- 24942745
TI  - Incidence of invasive CNS disease with Ureaplasma: where are we now?

PMID- 24942744
TI  - Small ubiquitin-like modifier (SUMO) protein-specific protease 1 de-SUMOylates
      Sharp-1 protein and controls adipocyte differentiation.
AB  - Adipocyte differentiation is regulated by a transcriptional cascade that mainly
      includes CCAAT/enhancer-binding protein family members and the nuclear receptor
      peroxisome proliferator-activated receptor gamma (PPARgamma). Here we show the
      defects in adipocyte differentiation as well as PPARgamma expression in Senp1(-/
      ) mouse embryonic fibroblast cells induced by adipogenic stimuli. We further
      determine that SENP1 is a specific de-SUMOylation protease for Sharp-1, a
      repressor for PPARgamma transcription and adipogenesis. SENP1 enhances
      adipogenesis through de-SUMOylation of Sharp-1, which then releases Sharp-1
      repression of PPARgamma expression and adipocyte differentiation. These results
      reveal SENP1 as a novel regulator in adipogenesis. 

PMID- 24942746
TI  - Effects of synchronisation during SiPAP-generated nasal intermittent positive
      pressure ventilation (NIPPV) in preterm infants.
AB  - OBJECTIVE: The SiPAP flow driver (Care Fusion, Dublin, Ohio, USA) offers
      synchronised nasal intermittent positive pressure ventilation (sNIPPV) using an
      abdominal capsule. This study aims to describe the accuracy and effects of
      synchronised NIPPV using SiPAP in preterm infants. DESIGN: Ten infants, born <28
      weeks' gestation, receiving synchronised SiPAP-generated NIPPV, in 'biphasic
      trigger' mode, were observed. Abdominal capsule signals, delivered pressures,
      respiratory pattern and oxygen saturations were recorded. Tidal volume (VT),
      apnoeas, proportion of breaths supported by SiPAP and time between inspiration
      onset and SiPAP pressure rise were analysed. RESULTS: Infants were of median
      26(+0) weeks' gestational age and birth weight 776 g. Mean (SD) respiratory rate
      (RR) was 53 (14)/min. 82% (17) of spontaneous breaths triggered a SiPAP pressure
      peak. Mean time between inspiration and SiPAP pressure rise was 28 (20) ms. There
      was no difference in VT when breaths triggered a SiPAP pressure peak compared
      with breaths without a pressure peak. No VT was generated by pressure peaks
      delivered during apnoea. Capsule signals were not recognised following >10% of
      breaths, resulting in asynchronous NIPPV delivery. Movements resulted in
      irregular SiPAP pressures and desaturation. When the RR was faster, >55/min,
      breaths irregularly triggered a SiPAP pressure peak (p=0.003). Compared with
      times when every breath resulted in a pressure peak, lower mean pressures were
      achieved, 7.9 vs 8.4 cm H2O (p=0.02). CONCLUSIONS: The SiPAP synchronisation
      system triggered rapidly with most spontaneous breaths, but did not result in
      larger tidal volumes. When the RR was >55/min, the SiPAP delivered fewer pressure
      peaks at lower pressures.

PMID- 24942747
TI  - Doctors urge WHO not to be swayed by tobacco industry in regulating e-cigarettes.

PMID- 24942748
TI  - Public Health Genomics joins forces with the Genomic Medicine Alliance.

PMID- 24942749
TI  - Applying RE-AIM to the evaluation of FUEL Your Life : a worksite translation of
      DPP.
AB  - Weight management programs are becoming increasingly common in workplace
      settings; however, few target middle-aged men. The purpose of this article is to
      describe the process evaluation of a worksite translation of the Diabetes
      Prevention Program in a predominantly middle-aged male population. The translated
      program, FUEL Your Life, was largely self-directed, with support from peer health
      coaches and occupational health nurses. The RE-AIM (Reach Effectiveness Adoption
      Implementation Maintenance) framework was used to examine the factors that
      influenced program implementation using data from an environmental assessment,
      participant surveys, peer health coach surveys, and occupational health nurse
      interviews. An overwhelming majority of the employees who enrolled in the study
      were overweight or obese (92%). Overall, the program was effective for weight
      maintenance; those with higher levels of participation and engagement had better
      weight loss outcomes. The peer health coach and family elements of the
      intervention were underused. The program was successful in reaching the intended
      population; however, the program had limited success in engaging this population.
      Not surprisingly, weight loss was a function of participant engagement and
      participation. Increasing participant engagement and participation is important
      to the success of weight management interventions translated to the worksite
      setting. Garnering buy-in and support from management can serve to increase the
      perceived importance of weight management in worksites. With management support,
      weight management protocols could be integrated as a component of the mandatory
      safety and health assessments already in place, fostering promotion of healthy
      weight in the workforce. 

PMID- 24942750
TI  - Evaluating school obesity-related policies using surveillance tools: lessons from
      the ScOPE study.
AB  - The evidence evaluating the association between school obestiy prevention
      policies and student weight is mixed. The lack of consistent findings may result,
      in part, from limited evaluation approaches. The goal of this article is to
      demonstrate the use of surveillance data to address methodological gaps and
      opportunities in the school policy evaluation literature using lessons from the
      School Obesity-Related Policy Evaluation (ScOPE) study. The ScOPE study uses a
      repeated, cross-sectional study design to evaluate the association between school
      food and activity policies in Minnesota and behavioral and weight status of youth
      attending those schools. Three surveillance tools are used to accomplish study
      goals: Minnesota School Health Profiles (2002-2012), Minnesota Student Survey
      (2001-2013), and National Center for Educational Statistics. The ScOPE study
      takes two broad steps. First, we assemble policy data across multiple years and
      monitor changes over time in school characteristics and the survey instrument(s),
      establish external validity, and describe trends and patterns in the distribution
      of policies. Second, we link policy data to student data on health behaviors and
      weight status, assess nonresponse bias, and identify cohorts of schools. To
      illustrate the potential for program evaluators, the process, challenges
      encountered, and solutions used in the ScOPE study are presented. 

PMID- 24942751
TI  - Knowledge, perceptions, and behaviors related to salt use among Philadelphia
      Chinese take-out restaurant owners and chefs.
AB  - Most of the sodium Americans consume comes from processed and restaurant foods.
      An upstream global strategy to promote health is to work with local restaurants
      to reduce sodium content in their food offerings, while accounting for food taste
      and economic considerations. In urban communities, Chinese take-out restaurants
      serve meals with large amounts of sodium and are clustered in low-income,
      racial/ethnic minority communities with a high prevalence of hypertension. The
      objective of this study is to assess baseline knowledge, attitudes, and behaviors
      related to sodium use/consumption among Chinese take-out owners and chefs
      recruited to participate in the Philadelphia Healthy Chinese Take-Out Initiative.
      A cross-sectional study of 221 Chinese take-out restaurants was conducted from
      August 2012 to February 2013. Items measured knowledge, attitudes, and behaviors
      related to salt use, salt consumption, and health. Most owners/chefs knew that
      excess sodium consumption contributes to high blood pressure but were less aware
      of other health effects and of major sources of sodium in the U.S. diet. The
      majority were willing and able to reduce sodium content in meals if customer
      demand could be maintained, and they desired training in food preparation,
      procurement, and marketing. Findings show a need to provide education,
      strategies, and support to Chinese take-out owners/chefs in preparing low-salt
      dishes. The results of this and future studies to reduce sodium content in meals
      by working with restaurant owners and chefs have global health promotion
      implications. 

PMID- 24942752
TI  - Thrombotic risk in patients with primary immune thrombocytopenia is only mildly
      increased and explained by personal and treatment-related risk factors.
AB  - BACKGROUND: An increased risk of thrombosis has been reported in primary immune
      thrombocytopenia (ITP) and with the use of thrombopoietin (TPO) receptor
      agonists, on the basis of population studies using administrative databases.
      OBJECTIVES: To evaluate if the incidence of venous and arterial thrombosis in
      patients with primary ITP is higher than a clinically significant cut-off set at
      of 3% and 6.4%. PATIENTS/METHODS: We undertook a retrospective multicenter
      investigation in a large cohort of patients requiring at least one treatment for
      ITP, enrolled from the major tertiary Italian centers treating ITP. A total of
      986 patients were analyzed. RESULTS: During a 3888 patient-year follow-up, 43
      first thrombotic events occurred: 28 arterial and 15 venous, resulting in a
      cumulative incidence of 3.2% for arterial (95% CI, 2.0-5.0) and 1.4% (95% CI, 0.8
      2.5) for venous thrombosis at 5 years. The annualized rates for 100 patient-years
      were 1.14 (95% CI, 0.84-1.54), 0.39 (95% CI, 0.23-0.65) and 0.71 (95% CI, 0.49
      1.04) for total, venous and arterial thrombosis. Splenectomy, performed in 136
      patients (13.7%), increased thrombotic risk (HR = 3.5, 95% CI) compared with non
      splenectomized patients. Age > 60 years, more than two risk factors for
      thrombosis at diagnosis and steroid use were independently associated with an
      increased risk of thrombosis. CONCLUSIONS: In this study, we demonstrate that the
      5-year cumulative incidence of venous and arterial thrombosis in ITP is well
      below the predefined thresholds. Venous and arterial thromboembolism are not
      frequent complications in ITP, except in particular settings, such as in
      splenectomized and elderly patients.

PMID- 24942754
TI  - Performance of the standardised MedDRA(r) queries for case retrieval in the
      French spontaneous reporting database.
AB  - OBJECTIVE: The objective of this study was to evaluate the performance of
      Standardised MedDRA(r) Queries (SMQs) in adverse drug reaction (ADR)
      identification. METHODS: ADR cases included in the last complete year of the
      French Pharmacovigilance database for research were used to test four SMQs
      (narrow and broad): agranulocytosis, demyelination, osteonecrosis and psychosis.
      Reference cases were identified by free-text search and validated by two authors.
      Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative
      predictive value (NPV) of narrow and broad searches of each SMQ were calculated
      and reported as proportions with 95% exact confidence interval (CI). RESULTS:
      Among 20,830 cases reported in 2009, 337 validated cases of agranulocytosis, 17
      of demyelination, 52 of osteonecrosis and 230 of psychosis were included in the
      reference sets. Estimations of SMQ narrow search performance were as follows: Se
      62.9% (95% CI 57.5-68.1) and PPV 46.8% (95% CI 42.1-51.5) for agranulocytosis; Se
      88.2% (95% CI 63.6-98.5) and PPV 34.1% (95% CI 20.5-49.9) for demyelination; Se
      94.2% (95% CI 84.1-98.8) and PPV 74.2% (95% CI 62.0-84.2) for osteonecrosis; and
      Se 75.1% (95% CI 69.0-80.6) and PPV 87.8% (95% CI 82.3-92.0) for psychosis.
      Results obtained using the broad search were similar except for PPV concerning
      osteonecrosis (52.7% [95% CI 42.1-63.1]) and psychosis (61.4% [95% CI 55.7
      66.8]). For all selected SMQs, Sp and NPV were greater than 98% for both narrow
      and broad searches. CONCLUSION: Heterogeneous performance of SMQs for case
      retrieval was found and seems to be related to the characteristics of the
      condition of interest. It could therefore be expected that for other SMQs,
      performance may be affected in the same manner.

PMID- 24942753
TI  - Nanovalve activation by surface-attached photoacids.
AB  - Proton transfer caused by excitation of a photoacid attached to the surface of a
      mesoporous silica nanoparticle activates a nanovalve and causes release of
      trapped molecules. The protonation of an aniline-based stalk releases a
      noncovalently bound cyclodextrin molecule that blocked a pore. The results show
      that pH-responsive molecular delivery systems can be externally controlled using
      light. 

PMID- 24942755
TI  - Readability assessment of package inserts of biological medicinal products from
      the European medicines agency website.
AB  - BACKGROUND: Package inserts that accompany medicines are a common source of
      information aimed at patients and should match patient abilities in terms of
      readability. OBJECTIVE: Our objective was to determine the degree of readability
      of the package inserts for biological medicinal products commercially available
      in 2007 and compare them with the readability of the same package inserts in
      2010. METHODS: A total of 33 package inserts were selected and classified into
      five groups according to the type of medicine: monoclonal antibody-based
      products, cytokines, therapeutic enzymes, recombinant blood factors and other
      blood-related products, and recombinant hormones. The package inserts were
      downloaded from the European Medicines Agency website in 2007 and 2010.
      Readability was evaluated for the entire text of five of the six sections of the
      package inserts and for the 'Annex' when there was one. Three readability
      formulas were used: SMOG (Simple Measure of Gobbledygook) grade, Flesh-Kincaid
      grade level, and Szigriszt's perspicuity index. RESULTS: No significant
      differences were found between the readability results for the 2007 package
      inserts and those from 2010 according to any of the three readability indices
      studied (p>0.05). However, there were significant differences (p<0.05) between
      the readability scores of the sections of the package inserts in both 2007 and
      2010. The readability of the package inserts was above the recommended sixth
      grade reading level (ages 11-12) and may lead to difficulties of understanding
      for people with limited literacy. CONCLUSIONS: All the sections should be easy to
      read and, therefore, the readability of the medicine package inserts studied
      should be improved.

PMID- 24942758
TI  - Making the World Health Assembly fit for the 21st century.

PMID- 24942757
TI  - Histological evaluation in ulcerative colitis.
AB  - This review summarizes diagnostic problems, challenges and advances in ulcerative
      colitis (UC). It emphasizes that, although histopathological examination plays a
      major role in the diagnosis and management of UC, it should always be interpreted
      in the context of clinical, endoscopic, and radiological findings. Accurate
      diagnosis requires knowledge of the classic morphological features of UC, as well
      as a number of atypical pathological presentations that may cause mis
      classification of the disease process, either in resection or biopsy specimens.
      These atypical pathological presentations include rectal sparing and patchiness
      of disease at initial presentation of UC in pediatric patients or in the setting
      of medically treated UC, cecal or ascending colon inflammation in left-sided UC,
      and backwash ileitis in patients with severe ulcerative pancolitis. Loosely
      formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt
      or eroded surface, should not be interpreted as evidence of Crohn's disease.
      Indeterminate colitis should only be used in colectomy specimens as a provisional
      pathological diagnosis. Patients with UC are at risk for the development of
      dysplasia and carcinoma; optimal outcomes in UC surveillance programs require
      familiarity with the diagnostic criteria and challenges relating to UC-associated
      dysplasia and malignancy. Colon biopsy from UC patients should always be
      evaluated for dysplasia based on cytological and architectural abnormalities.
      Accurate interpretation and classification of dysplasia in colon biopsy from UC
      patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or
      dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic
      correlation. Isolated polypoid dysplastic lesions are considered to be sporadic
      adenoma if occurring outside areas of histologically proven colitis, or adenoma
      like dysplasia if occurring in the diseased segment. Recent data suggest that
      such lesions may be treated adequately by polypectomy in the absence of flat
      dysplasia in the patient. UC patients with DALM or flat high-grade dysplasia
      should be treated by colectomy because of the high probability of adenocarcinoma.
      The natural history of low-grade dysplasia (LGD) is more controversial: while
      multifocal LGD, particularly if detected at the time of initial endoscopic
      examination, is treated with colectomy, unifocal flat LGD detected during
      surveillance may be managed by close follow-up with increased surveillance. The
      surveillance interval and treatment options for UC patients with dysplasia are
      reviewed in detail. 

PMID- 24942759
TI  - Combination of phytochemicals as adjuvants for cancer therapy.
AB  - Newer treatments of advanced human cancer are based on combination of cancer
      drugs that have different mechanism of actions yet the combination strategy may
      potentiate the anti-cancer effects and cytotoxicity. Recent studies suggest that
      cancer growth can be inhibited more effectively by combination of phytochemicals
      that affect different pathways. The apoptotic activity can be modulated by
      intrinsic and extrinsic molecules. The combination of anti-tumor phytochemicals
      can be more effective in modulating different signaling pathways associated with
      tumor cell growth which is the common target for anti-tumor action. Combinations
      of cytotoxic anti-tumor agents and inhibitors from phytochemicals are believed to
      act together producing inhibitory mechanisms on cancer growth. This combination
      strategy shows promise on cancer therapy. However, the combination of
      phytochemicals in cancer therapy needs to be further investigated to develop a
      better treatment strategy. Recent patents on anti-tumor phytochemicals are
      reviewed in this article. 

PMID- 24942756
TI  - Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of
      immune regulation.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is considered a "nonimmunogenic"
      neoplasm. Single-agent immunotherapies have failed to demonstrate significant
      clinical activity in PDAC and other "nonimmunogenic" tumors, in part due to a
      complex tumor microenvironment (TME) that provides a formidable barrier to immune
      infiltration and function. We designed a neoadjuvant and adjuvant clinical trial
      comparing an irradiated, granulocyte-macrophage colony-stimulating factor (GM
      CSF)-secreting, allogeneic PDAC vaccine (GVAX) given as a single agent or in
      combination with low-dose cyclophosphamide to deplete regulatory T cells (Treg)
      as a means to study how the TME is altered by immunotherapy. Examination of
      resected PDACs revealed the formation of vaccine-induced intratumoral tertiary
      lymphoid aggregates in 33 of 39 patients 2 weeks after vaccine treatment.
      Immunohistochemical analysis showed these aggregates to be regulatory structures
      of adaptive immunity. Microarray analysis of microdissected aggregates identified
      gene-expression signatures in five signaling pathways involved in regulating
      immune-cell activation and trafficking that were associated with improved
      postvaccination responses. A suppressed Treg pathway and an enhanced Th17 pathway
      within these aggregates were associated with improved survival, enhanced
      postvaccination mesothelin-specific T-cell responses, and increased intratumoral
      Teff:Treg ratios. This study provides the first example of immune-based therapy
      converting a "nonimmunogenic" neoplasm into an "immunogenic" neoplasm by inducing
      infiltration of T cells and development of tertiary lymphoid structures in the
      TME. Post-GVAX T-cell infiltration and aggregate formation resulted in the
      upregulation of immunosuppressive regulatory mechanisms, including the PD-1-PD-L1
      pathway, suggesting that patients with vaccine-primed PDAC may be better
      candidates than vaccine-naive patients for immune checkpoint and other
      immunomodulatory therapies.

PMID- 24942766
TI  - Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory
      blood pressure in moderate-to-severe hypertensive patients not controlled by
      amlodipine alone.
AB  - This previously unpublished, preplanned analysis investigated the efficacy of the
      olmesartan/amlodipine combination at different doses on 24-h blood pressure (BP)
      control, as well as assessed trough estimation of trough-to-peak ratio (TPR) and
      smoothness index (SI). Ambulatory BP monitoring was performed in patients with
      moderate-to-severe hypertension whose BP was inadequately controlled after 8
      weeks' treatment with amlodipine 5 mg. Patients were randomized to continue with
      amlodipine 5 mg or to receive olmesartan/amlodipine 10/5, 20/5 or 40/5 mg for 8
      weeks (Period II). Patients not achieving BP control were uptitrated to a more
      powerful regimen for another 8 weeks (Period III). During Period II, each
      olmesartan/amlodipine combination reduced 24-h systolic and diastolic BP
      (SBP/DBP), as well as morning and early morning SBP/DBP, significantly more than
      amlodipine 5 mg (P<0.001 for all). TPRs were higher in each olmesartan/amlodipine
      group than with amlodipine 5 mg, and SI values showed dose-related increases;
      olmesartan/amlodipine 40/5 mg produced a significantly higher SI for SBP and DBP
      (1.55 and 1.33, respectively) than amlodipine 5 mg (0.96 and 0.77, respectively,
      P<0.0001 for each). During Period III, uptitrated patients showed further BP
      reductions, which were largest in those on olmesartan/amlodipine 40/10 mg. SI
      values increased in uptitrated patients and were highest with
      olmesartan/amlodipine 40/10 mg (SBP 1.62/DBP 1.41). The olmesartan/amlodipine
      combination effectively reduces BP over 24 h, including the morning hours, in a
      dose-related manner. Compared with amlodipine alone, the olmesartan/amlodipine
      combination has a better 24-h coverage (TPR) and a dose-related improvement in BP
      lowering homogeneity (SI). 

PMID- 24942767
TI  - Do we understand the relationship between left ventricular structural remodeling
      and stroke in arterial hypertension?

PMID- 24942768
TI  - Autonomic nervous activation triggered during induction of reactive hyperemia
      exerts a greater influence on the measured reactive hyperemia index by peripheral
      arterial tonometry than on flow-mediated vasodilatation of the brachial artery in
      patients with hypertension.
AB  - Flow-mediated vasodilatation of the brachial artery (FMD) and reactive hyperemia
      index (RHI) measured by peripheral arterial tonometry are known to be weakly
      associated with one another, but the mechanisms underlying this weak association
      remain to be clarified. We examined whether the autonomic nervous activation
      induced by the 5 min forearm clamping used to induce reactive hyperemia might
      exert any influence on the FMD and RHI in subjects with hypertension. In 115
      subjects with hypertension (age 61+/-1 years), the FMD and RHI were measured
      simultaneously, and the heart rate variability (HRV) parameters (low-frequency
      component (LF), high-frequency component (HF), and the ratio (LF/HF) between the
      two) were calculated from the electrocardiographic recordings obtained before and
      after the start of forearm clamping. A multivariate linear regression analysis
      with adjustments for confounding variables demonstrated that the RHI, but not the
      FMD, was significantly associated with the percent change of the LF/HF associated
      with forearm clamping (beta=-0.204, P=0.043). In conclusion, autonomic nervous
      system activation, especially sympathetic activation, induced by 5-min forearm
      clamping utilized to provoke reactive hyperemia may significantly affect the RHI
      rather than FMD in subjects with hypertension. 

PMID- 24942769
TI  - Fetal programming by high-sucrose diet during pregnancy affects the vascular
      angiotensin II receptor-PKC-L-type Ca(2+) channels (Cav1.2) axis to enhance
      pressor responses.

PMID- 24942770
TI  - Safety, efficacy and renal effect of febuxostat in patients with moderate-to
      severe kidney dysfunction.
AB  - Hyperuricemia (HU) is common in patients with chronic kidney disease (CKD), and
      accumulating evidence suggests it has a pathogenic role in the progression of the
      disease. However, a major challenge in treating patients with HU is the adverse
      effects caused by urate-lowering drugs used to treat CKD. Because of these
      untoward effects, doses need to be reduced, which leads to suboptimal efficacy.
      Febuxostat has been shown to be highly efficacious in reducing serum uric acid
      (sUA) and is well tolerated in patients with mild kidney dysfunction. However,
      its safety and efficacy have not been well studied in more advanced cases of CKD.
      We studied the safety and efficacy of escalating doses of febuxostat over a 24
      week period in 70 patients with CKD stages 3b, 4 and 5, and we also observed the
      changes in blood pressure, estimated glomerular filtration rate (eGFR) and
      proteinuria following the reduction of sUA. Drug-related adverse events (AEs)
      occurred in only 5 out of 70 patients. All but one of the events were mild, and
      all five patients fully recovered. By 24 weeks, the reduction of sUA levels was
      >40% in CKD stage 3b and >50% in CKD stages 4 and 5. More than 70% of patients
      achieved target sUA levels of 6 mg dl(-1) or less. Multivariate analysis showed
      that a greater reduction in sUA with febuxostat was associated with an increase
      in eGFR and a tendency toward decreased proteinuria. Febuxostat was safe and
      efficacious in the treatment of CKD stages 3b-5. 

PMID- 24942771
TI  - Editorial comment to extracorporeal shockwave therapy in the treatment of
      erectile dysfunction: a prospective, randomized, double-blinded, placebo
      controlled study.

PMID- 24942772
TI  - The beneficial effect of abatacept in lupus nephritis may include stabilization
      of beta1 integrin activation in podocytes and Treg cell repopulation: comment on
      the article by Furie et al.

PMID- 24942773
TI  - Expression patterns of chitinase and chitosanase produced from Bacillus cereus in
      suppression of phytopathogen.
AB  - Bacillus cereus MP-310 was incubated on various culture media substrates as LB,
      colloidal chitin, chitosan powder, and chitosan beads to investigate the
      concurrent expression patterns of chitinase and chitosanase isozymes by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Chitinase activity
      increased rapidly with a maximum level after 6 days of incubation in CM-chitin
      medium. Major bands of chitinase isozymes were strongly expressed on SDS-PAGE in
      LB medium (four bands) and in colloidal chitin medium (five bands) after 6 days
      after incubation, and in chitosan powder medium (one band) and in chitosan beads
      medium (five bands) after 12 days after incubation. A major band of chitosanase
      isozymes was strongly expressed on SDS-PAGE in chitosan powder medium (one band)
      and in chitosan beads medium (one band) after 12 days of incubation. 

PMID- 24942775
TI  - Exploration of Social, Environmental, and Familial Influences on the Sexual
      Health Practices of Urban African American Adolescents.
AB  - Despite efforts to examine social influences and provide interventions that lead
      to safer sexual practices for African American (AA) adolescent girls, statistics
      have demonstrated this population continues to have the highest rates of teen
      pregnancy and sexually transmitted infections (STIs) including HIV when compared
      with adolescent girls of other races. Guided by the principles of Black Feminist
      Thought and Photovoice and focus group methodology, this descriptive study aimed
      to discover the social realities influencing a group of eight AA adolescent girls
      aged 15 to 19 years. Data from individual interviews and a focus group session
      were collected from November 11, 2012, to February 1, 2013. Analysis of selected
      photographs, interviews, and focus group conversations through a feminist lens
      suggests AA adolescents of low socioeconomic status continue to foster racial and
      mental inferiority stereotypes by using their sexuality as a bargaining tool for
      acceptance, value, and even love. 

PMID- 24942774
TI  - The Effects of a School-Based Atopy Care Program for School-Aged Children.
AB  - The aim of the present study was to evaluate the effectiveness of a school-based
      atopy care program (SACP) for children with atopic dermatitis (AD). The program
      is administered by health teachers who are also school nurses. The study compared
      groups using a pre- and post-test design. Participants were children with AD and
      their parents (98 dyads; 32 in the test group and 66 in the control group)
      sampled from four elementary schools in Seoul. After completing the SACP, parents
      in the test group had significantly increased knowledge of AD (p = .04) and a
      greater sense of parental efficacy (p = .02) when compared with the control
      group. This study derived guidelines that elementary health teachers can use in
      practice for school-aged children with AD. We concluded that there is sufficient
      evidence of effectiveness for the SACP to be used as a model for chronic disease
      management in school-aged children. 

PMID- 24942776
TI  - Superficial malignant peripheral nerve sheath tumor arising from diffuse
      neurofibroma in a neurofibromatosis type 1 patient.
AB  - Malignant peripheral nerve sheath tumors (MPNST) are regarded as sarcomas that
      arise from peripheral nerves or that display differentiation along the lines of
      the various elements of the nerve sheath. These tumors occur in deep soft
      tissues, but superficial primary MPNST with a cutaneous or subcutaneous origin
      have rarely been reported. A 70-year-old woman presented with a 3-4-year history
      of a slowly enlarging soft nodule on the left side of her neck. The
      histopathological diagnosis of the nodule was low-grade MPNST arising from
      diffuse neurofibroma. There was increased cellularity, but no necrosis or mitotic
      activity. These histopathological findings pose difficulties in differential
      diagnosis from a neurofibroma with atypical histological features. We report a
      rare case of superficial MPNST arising from diffuse neurofibroma associated with
      underlying occipital bone dysplasia in a neurofibromatosis type 1 patient. 

PMID- 24942777
TI  - Early netrin-1 expression impairs central nervous system remyelination.
AB  - OBJECTIVE: Chronically demyelinated multiple sclerosis (MS) lesions are
      frequently characterized by scarce undifferentiated oligodendrocyte progenitor
      cells (OPCs), suggesting the exhaustion of a local OPC pool followed by failure
      of recruitment and differentiation. Stimulating prompt OPC recruitment following
      demyelination could improve myelin repair by providing sufficient numbers of
      remyelinating cells during the repair-permissive period. Understanding mechanisms
      that determine this process may have important therapeutic implications. We
      therefore investigated the role of the guidance molecule netrin-1 in OPC
      recruitment and central nervous system (CNS) remyelination. METHODS: Netrin-1
      expression was analyzed immunohistochemically in different types of MS lesions
      and in the murine lysolecithin model of demyelination. The influence of netrin-1
      on CNS remyelination was examined using gain and loss of function experiments.
      RESULTS: We show that in MS lesions, astrocytes upregulate netrin-1 expression
      early during demyelination and netrin-1 receptors are expressed by OPCs. In
      contrast, in the efficiently repairing lysolecithin model of demyelination
      (astrocyte-free), netrin-1 expression is absent during early phases and detected
      concomitant with completion of OPC recruitment. In vitro migration assays
      demonstrated that netrin-1 is a chemorepellent for migrating adult OPCs. In mouse
      lesions, antibody-mediated disruption of netrin-1 function at the peak phase of
      recruitment increased OPC numbers. Conversely, lentiviral-mediated induction of
      netrin-1 expression prior to OPC recruitment reduced the number of cells
      recruited and impaired remyelination. INTERPRETATION: Our findings support the
      conclusion that netrin-1 expression within demyelinating MS plaques blocks OPC
      recruitment, which with repeated demyelinating episodes contributes to permanent
      remyelination failure.

PMID- 24942778
TI  - Evaluation of phylogenetic relationships in Lemnaceae using nuclear ribosomal
      data.
AB  - Nuclear DNA sequence data are essential for obtaining a complete understanding of
      plant species relationships, yet these data have been conspicuously absent from
      phylogenetic analyses of Lemnaceae (duckweeds). Using a modified Sanger
      sequencing protocol, we obtained DNA sequences of duckweed nuclear ribosomal
      regions, including 18S and 26S rDNA genes, the external transcribed spacer (ETS)
      and the frequently used internal transcribed spacer (ITS). After obtaining
      sequence data for all Lemnaceae species, we ascertained that prior difficulty in
      sequencing the ITS regions likely resulted from extremely rigid secondary
      structures, precipitated by a high proportion of G/C nucleotides. In phylogenetic
      analyses, nuclear ribosomal data largely supported relationships that had been
      inferred using chloroplast DNA sequence data. 

PMID- 24942779
TI  - Letter by Mezzaroma, et al regarding article, "NLRP3 inflammasome as a
      therapeutic target in myocardial infarction".

PMID- 24942780
TI  - Reply to letter regarding article, "NLRP3 inflammasome as a therapeutic target in
      myocardial infarction".

PMID- 24942781
TI  - General practitioner management plans delaying time to next potentially
      preventable hospitalisation for patients with heart failure.
AB  - BACKGROUND: Several studies have shown that the Australian Medicare-funded
      chronic disease management programme can lead to improvements in care processes.
      No study has examined the impact on long-term health outcomes. AIMS: This
      retrospective cohort study assessed the association between provision of a
      general practitioner management plan and time to next potentially preventable
      hospitalisation for older patients with heart failure. METHODS: We used the
      Australian Government Department of Veterans' Affairs (DVA) claims database and
      compared patients exposed to a general practitioner management plan with those
      who did not receive the service. Kaplan-Meier analysis and Cox proportional
      hazards models were used to compare time until next potentially preventable
      hospitalisation for heart failure between the exposed and unexposed groups.
      RESULTS: There were 1993 patients exposed to a general practitioner management
      plan and 3986 unexposed patients. Adjusted results showed a 23% reduction in the
      rate of potentially preventable hospitalisation for heart failure at any time
      (adjusted hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.92; P = 0.0051)
      among those with a general practitioner management plan compared with the
      unexposed patients. Within one year, 8.6% of the exposed group compared with
      10.7% of the unexposed group had a potentially preventable hospitalisation for
      heart failure. CONCLUSIONS: A general practitioner management plan is associated
      with delayed time to next potentially preventable hospitalisation for heart
      failure.

PMID- 24942782
TI  - Rapidly reversible multiorgan failure after ingestion of "Molly" (pure 3,4
      methylenedioxymethamphetamine): a case report.
AB  - INTRODUCTION: "Molly" is a street name for pure 3,4
      methylenedioxymethamphetamine, an amphetamine derivative which acts by enhancing
      the release of neurotransmitters such as serotonin, dopamine and norepinephrine.
      This produces euphoria, increased sensory awareness and central stimulation that
      make it a popular club drug. Nevertheless, it is also associated with serious
      side effects. We report an unusual case of rapid multiorgan failure after
      ingestion of "Molly". Unlike previously described patterns of 3,4
      methylenedioxymethamphetamine-related organ failure, our case does not appear to
      be related to hyperthermia, rhabdomyolysis or hyponatremia. CASE PRESENTATION: A
      24-year-old Hispanic man presented to our hospital with an episode of seizure and
      subsequently developed acute kidney injury, respiratory failure requiring
      mechanical ventilation and congestive heart failure after ingestion of "Molly".
      He rapidly recovered with supportive care and was discharged home. CONCLUSIONS:
      The spectrum of complications associated with 3,4-methylenedioxymethamphetamine
      is wide and patient presentation may vary. Moreover, there appears to be multiple
      mechanisms involved in organ failure. Drug toxicity should be suspected while
      evaluating a patient with multisystem organ failure of unclear etiology.
      Treatment is generally supportive sometimes requiring mechanical ventilation and
      hemodialysis. Nevertheless, complete reversal of organ failure can be expected.

PMID- 24942783
TI  - Endoscopic component separation for ventral hernia causes fewer wound
      complications compared to open components separation: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Open component separation (OCS) for tension-free approximation of
      fascial borders is increasingly used for repair of large midline ventral hernias.
      Recent studies suggested lower complication rates following a modified version of
      this technique with an endoscopic approach (ECS). The aim of this meta-analysis
      was to compare the outcomes after ECS and OCS. METHODS: A literature search was
      performed in PubMed and Embase in order to identify studies comparing ECS and OCS
      as a supplementary procedure for surgical repair of ventral hernia. The included
      studies were independently assessed using the Newcastle Ottawa Scale. Outcomes
      analyzed were wound complications, hernia recurrence and length of stay. A meta
      analysis on the pooled data was performed. RESULTS: The literature search
      identified 222 articles, of which five retrospective comparative cohort studies
      were included in the review and meta-analysis reporting on a total of 163
      patients. Patient demography and the rates of mesh repair were comparable between
      the ECS and OCS patient groups. The incidence of wound complications comprising
      surgical site infection, skin necrosis, subcutaneous abscess, seroma, skin
      dehiscence, cellulitis, and fistula was significantly less after ECS (odds ratio
      [OR] 0.27, 95 % confidence interval [CI] 0.12-0.58, p < 0.001). The incidence of
      recurrent hernia was 13 % after ECS and 16 % after OCS (OR 0.76, 95 % CI 0.29
      1.98, p = 0.57). Four studies reported length of stay that was comparable between
      the groups (mean difference -0.14 days, 95 % CI -1.49 to 1.21, p = 0.84).
      CONCLUSIONS: ECS causes fewer wound complications compared with OCS.

PMID- 24942785
TI  - Sarcoma after 5 years of progression-free survival: lessons from the French
      sarcoma group.

PMID- 24942784
TI  - Endoscopic transpapillary stenting for pancreatic fistulas after necrosectomy
      with necrotizing pancreatitis.
AB  - BACKGROUND: Data concerning the incidence and treatment of pancreatic fistula
      after necrosectomy in severe acute necrotizing pancreatitis (SAP) are scarce. Our
      aim was to assess the incidence of pancreatic fistula, and the feasibility and
      results of endoscopic transpapillary stenting (ETS) in patients with SAP after
      necrosectomy. METHODS: From January 2009 to December 2012 twenty-nine consecutive
      patients with SAP and necrosectomy in Oulu University Hospital were enrolled into
      this study. Five patients died before ETS because of the rapid progress of the
      disease and were, therefore, excluded. RESULTS: ERP was performed for the
      remaining 24 patients demonstrating fistula in 22/24 patients (92 %). ETS was
      successful in 23 patients and the fistula closed in all of them after a median of
      82 (2-210) days with acceptable morbidity and no procedure-related mortality.
      CONCLUSION: All patients after necrosectomy for SAP seem to have internal or
      external pancreatic fistula. EST aimed at internal drainage of the necrosectomy
      cavity is a feasible and effective therapy in these patients.

PMID- 24942786
TI  - Growth in working memory and inhibition predicts literacy in English language
      learners: a cross-sectional and longitudinal study.
AB  - The purpose of this study was to determine whether cross-sectional and growth
      effects in second language (L2) literacy are related to the executive component
      of working memory (WM) and whether inhibition may underlie the links between WM
      and reading in children whose first language (L1) is Spanish. Elementary school
      children (grades 1, 2 and 3) were administered a battery of cognitive [WM, short
      term memory (STM), random generation, rapid naming, phonological processing],
      vocabulary and reading measures in both Spanish (L1) and English (L2) in Year 1
      and again one year later. The regression analyses showed that L2 growth in WM
      significantly predicted growth in L2 reading skills even when inhibition was
      controlled. Further, the contributions of WM to reading growth in both L1 and L2
      reading were independent of cross-language skills in phonological processing,
      STM, oral language and naming speed. Overall, the results suggest the mental
      activities that underlie WM and inhibition in predictions of L2 literacy reflect
      independent executive processes. 

PMID- 24942787
TI  - Carmustine (BCNU) plus Teniposide (VM26) in recurrent malignant glioma.
AB  - BACKGROUND: After the failure of radiotherapy and temozolomide, there is no
      established standard therapy for patients with recurrent glioblastoma (GBM).
      Based on the promising data of a previous trial (NOA-01) for primary GBM and some
      retrospective case series for GBM recurrence, the combination of nimustine and
      teniposide (VM26) was commonly used in this setting. When nimustine was no longer
      available in Europe, we switched to intrvaveneous carmustine (BCNU). Data on the
      toxicity and efficacy of BCNU and VM26 in recurrent GBM are lacking. METHODS: In
      our neurooncological center, all patients with recurrent GBM or with progressed
      glioma and a typical MRI lesion suggesting GBM treated with BCNU (130-150
      mg/m(2), day 1/42) and VM26 (45-60 mg/m(2), days 1-3/42) were analyzed
      retrospectively for progression-free survival, overall survival and toxicity.
      RESULTS: Fifteen patients (median age 52 years) were identified. Median
      progression-free survival was 2 months and median overall survival was 4 months.
      Two patients (14%) developed grade 3/4 hematotoxicity. Nonhematological toxicity
      >=grade 3 was not observed. CONCLUSION: Our data do not support the application
      of BCNU/VM26 in patients with late stages of recurrent GBM.

PMID- 24942788
TI  - Time course of oocyte development in winter flounder Pseudopleuronectes
      americanus and spawning seasonality for the Gulf of Maine, Georges Bank and
      southern New England stocks.
AB  - Winter flounder Pseudopleuronectes americanus were collected at monthly intervals
      from December 2009 to May 2011, to describe the pattern and seasonality of oocyte
      development, including: (1) the group-synchronous transition from primary to
      secondary oocytes that initiates immediately after spawning, (2) the slow
      (months) development of vitellogenic oocytes followed by the rapid (weeks)
      maturation of oocytes, (3) the synchronous nature of mature oocytes ovulating,
      but the discrete releases of benthic eggs in batches, (4) the protracted (months)
      degradation of postovulatory follicles and (5) the occurrence of follicular
      atresia. Although fish were collected across only c. 2 degrees  latitudinal
      range, the spawning season was c. 1 month later in the Gulf of Maine (GOM) than
      on Georges Bank and in southern New England. This is probably due to lower
      temperatures in the GOM. These stock-specific data regarding the time course of
      oogenesis are of practical value. This information is discussed in relation to
      measuring and interpreting elements of reproductive potential such as maturation,
      skipped spawning and fecundity, the response of reproductive traits by this
      widely distributed species to changing climate and the response by this common,
      marine-estuarine species to urbanization, particularly environmental pollutants
      and dredging. 

PMID- 24942791
TI  - General malaise and physical symptoms in young women with untouched toe.
AB  - Untouched toe is a condition in which a toe does not touch the ground while
      standing. It is frequently observed in women even under physiological conditions.
      Deformities or symptoms of the toes are not observed in these women. The clinical
      significance of untouched toe has not been fully elucidated. Two hundred young
      healthy women were recruited into the present study after informed consent. We
      evaluated the prevalence of untouched toe by measuring various indexes of the toe
      using a foot-sole-measuring equipment. We also conducted a self-administered
      questionnaire regarding general malaise. Untouched toe was observed in 114 of
      these 200 women (57.0%). The fifth toe was more frequently affected than the
      other toes. There were no significant differences in size of foot except the area
      and proportion touching the ground between women with untouched toe and those
      without untouched toe. The prevalence of general malaise was significantly higher
      in women with at least one untouched toe (57.0%) compared with those without
      untouched toe (43.0%) (p<0.05). Twelve symptoms-irritability, headache, tired
      eyes, hazy vision, congested or runny nose, irregular menstruation or menstrual
      pain, shoulder stiffness, neck stiffness, low back pain, cold hands, swollen
      feet, and cold feet-were more frequently observed in women with at least one
      untouched toe compared with those without untouched toes. Untouched toe was
      associated with various symptoms of general malaise. However, the pathological
      mechanism by which untouched toe causes these symptoms has not been determined.
      Further analysis of gait and exercise habits in women with untouched toe is
      necessary.

PMID- 24942790
TI  - Association of dietary fat and carbohydrate consumption and predicted ten-year
      risk for developing coronary heart disease in a general Japanese population.
AB  - We examined the relationships between dietary carbohydrate, protein, fat, and the
      ratio of n6/n3 fatty acid intakes with the predicted 10-year coronary heart
      disease (CHD) risk in a general Japanese population. We used the Framingham risk
      score to determine the 10-year CHD risk of the subjects, who were employees of 6
      companies in a single prefecture in Japan. After excluding the subjects who
      reported any history of angina pectoris, myocardial infarction, diabetes, or
      cancer, and those with missing data resulting in the inability of estimation of
      10-year CHD risk and food intakes, the final data analysis was carried out for
      809 subjects. The logistic regression models revealed a significantly increased
      odds ratio of 10-year CHD risk in the subjects with the highest tertile of
      carbohydrate intake (% energy) (odds ratio 3.64, 95% CI, 2.07-6.40); after
      adjustment for other variables, the odds ratio for the 10-year CHD risk was also
      higher in the subjects with the highest tertile of carbohydrate intake (odds
      ratio 1.72, 95% CI, 0.70-4.25). We also found that fat intake and the ratio of
      n6/n3 fatty acids were inversely associated with the predicted 10-year CHD risk
      (p for trend<0.01). The present findings added evidence of a positive association
      of dietary carbohydrate and inverse associations of total fat and n6/n3 fatty
      acid ratio with the predicted 10-year CHD risk in a general Japanese population.

PMID- 24942789
TI  - Changes in antidepressant use by young people and suicidal behavior after FDA
      warnings and media coverage: quasi-experimental study.
AB  - OBJECTIVE: To investigate if the widely publicized warnings in 2003 from the US
      Food and Drug Administration about a possible increased risk of suicidality with
      antidepressant use in young people were associated with changes in antidepressant
      use, suicide attempts, and completed suicides among young people. DESIGN: Quasi
      experimental study assessing changes in outcomes after the warnings, controlling
      for pre-existing trends. SETTING: Automated healthcare claims data (2000-10)
      derived from the virtual data warehouse of 11 health plans in the US Mental
      Health Research Network. PARTICIPANTS: Study cohorts included adolescents (around
      1.1 million), young adults (around 1.4 million), and adults (around 5 million).
      MAIN OUTCOME MEASURES: Rates of antidepressant dispensings, psychotropic drug
      poisonings (a validated proxy for suicide attempts), and completed suicides.
      RESULTS: Trends in antidepressant use and poisonings changed abruptly after the
      warnings. In the second year after the warnings, relative changes in
      antidepressant use were -31.0% (95% confidence interval -33.0% to -29.0%) among
      adolescents, -24.3% (-25.4% to -23.2%) among young adults, and -14.5% (-16.0% to 
      12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621
      dispensings per 100,000 people among adolescents, young adults, and adults,
      respectively. Simultaneously, there were significant, relative increases in
      psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9%
      to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, 
      6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per
      100,000 people among adolescents and young adults, respectively (approximately 77
      additional poisonings in our cohort of 2.5 million young people). Completed
      suicides did not change for any age group. CONCLUSIONS: Safety warnings about
      antidepressants and widespread media coverage decreased antidepressant use, and
      there were simultaneous increases in suicide attempts among young people. It is
      essential to monitor and reduce possible unintended consequences of FDA warnings
      and media reporting.

PMID- 24942793
TI  - Alternative placement of bispectral index electrode for monitoring depth of
      anesthesia during neurosurgery.
AB  - In neurosurgery in particular, the recommended placement of electrodes for
      monitoring depth of anesthesia during surgery sometimes conflicts with the
      surgical site or patient positioning. Therefore, we proposed this study to
      evaluate the agreement and correlation of bispectral index values recorded from
      the usual frontal area and the alternate, post-auricular areas in neurosurgery
      patients. Thirty-four patients scheduled for neurosurgery under general
      anesthesia were included. Bispectral index (BIS) sensors were placed at both the
      frontal and post-auricular areas. The anesthesia given was clinically adjusted
      according to the frontal (standard) BIS reading. The BIS values and impedance
      were recorded;Pearson's correlation and Bland-Altman plots were analyzed. The
      bias+/-2SD for the electrode placement before, during, and post-anesthesia were
      0+/-23.32, 1.5+/-10.69, and 2.1+/-13.52, while the limits of agreement were -23.3
      to 23.3, -12.2 to 9.2, and -17.7 to 13.5, respectively. The correlation
      coefficient between frontal- and post-auricular-area electrodes was 0.74 with a p
      value<0.001.The post-auricular placement of a BIS electrode is a practical
      alternative to frontal lobe placement. Nevertheless, proper electrode location is
      important to minimize error.

PMID- 24942792
TI  - Association of leptin and adiponectin levels with three-year weight change among
      Japanese male workers.
AB  - The purpose of this study was to clarify, through a prospective study, the
      relationship between leptin and adiponectin levels, and subsequent weight change.
      The study subjects were 2,485 male office workers aged 35-64 employed by a
      company in Fukuoka Prefecture, Japan. Of these men, 1,936 (77.9%) received health
      check-ups both in 2005-2007 and 3 years later, in 2008-2010. Of the subjects who
      received both health check-ups, 352 were excluded duo to cancer, cardiac
      infarction, stroke or diabetes mellitus, leaving a total of 1,584. We divided
      them into tertiles according to baseline leptin and adiponectin levels, and
      compared the subsequent change in body mass index (BMI) over 3 years. The
      subjects with the lowest leptin levels showed a significantly greater increase in
      BMI (difference in change in BMI=0.178 kg/m2, 95% CI:0.025-0.331 kg/m2) over 3
      years when those with the highest leptin levels were regarded as the reference
      even after adjusting for age, baseline BMI, smoking status, drinking status and
      exercise. The subjects with the highest adiponectin levels showed a greater
      increase in BMI (difference in change in BMI=0.099 kg/m2, 95% CI: -0.034-0.231
      kg/m2) over 3 years when those with the lowest adiponectin levels were regarded
      as the reference, but this association was not statistically significant after
      adjusting for age, baseline BMI, smoking status, drinking status and exercise.
      Our findings suggest that higher leptin levels may suppress weight gain in
      Japanese male workers.

PMID- 24942794
TI  - Usefulness of high mobility group box 1 protein as a plasma biomarker in patient
      with peripheral artery disease.
AB  - Atherosclerosis is often associated with chronic vascular inflammation. High
      mobility group box 1 protein (HMGB1) plays various roles, not only as a
      transcriptional regulatory factor in the nucleus, but also as an inflammatory
      mediator. A previous study suggested that fibrinogen is an important factor
      associated with atherosclerosis progression. The present study was performed to
      examine the levels of plasma HMGB1 protein in atherosclerosis patients. We
      studied 24 patients with peripheral artery disease (PAD) with atherosclerosis,
      and 10 healthy controls. We found that the concentrations of HMGB1 were increased
      in the plasma of the patients with atherosclerosis, and there were significant
      correlations between the plasma HMGB1 and fibrinogen levels. Plasma HMGB1 may
      play a key role in the pathogenesis of clinical and experimental atherosclerosis.

PMID- 24942795
TI  - Biallelic disruption of the PTCH1 gene in multiple basal cell carcinomas in
      Japanese patients with nevoid basal cell carcinoma syndrome.
AB  - The aim of the present study is to address whether the molecular pathogenesis is
      identical among multiple basal cell carcinomas (BCCs) present in the same nevoid
      basal cell carcinoma syndrome (NBCCS) patient. Patient 1 is a 61-year-old (yo)
      Japanese female whose clinical characteristics and findings of a genetic analysis
      of PTCH1 have been previously described. Patient 2 is patient 1's 64-yo sister
      who also suffered from NBCCS with a single base deletion at nucleotide 2613 in
      exon 16 (c.2613delC) in one PTCH1 allele. Thirteen and 3 independent specimens of
      BCC were applied for a molecular analysis of loss of heterozygosity (LOH) in
      PTCH1 in patients 1 and 2, respectively. Of particular note is that all BCC
      specimens examined showed a loss of the wild-type allele of exon 16 in PTCH1,
      thus indicating that LOH results in the biallelic disruption of PTCH1 in multiple
      BCCs that develop in an age- and location-independent manner in the same patient.
      These results indicate that the germline single base deletion of PTCH1 (c.2613
      delC) is a first hit and the LOH of the wild-type allele is a second hit,
      implying that all 16 BCCs detected in these NBCCS sisters fit the standard two
      hit model. 

PMID- 24942796
TI  - A case of vascular graft infection caused by Staphylococcus lugdunensis after
      femoropopliteal bypass operation.
AB  - A 79-year-old man who had undergone a right femoropopliteal (FP) bypass operation
      6 weeks previously was diagnosed with vascular graft infection caused by
      Staphylococcus lugdunensis. Another FP bypass operation was performed, with long
      term administration of antibiotics, and the patient eventually recovered well
      without any recurrences for over 2 years. Although S. lugdunens is classified as
      coagulase-negative Staphylococcus, its pathogenicity has been reported to be
      equal to that of S. aureus. Based on the literature review, the organism
      characteristically colonizes the inguinal area of human skin;thus, operations
      such as FP bypass grafting may place patients at a relatively high risk for
      infection by S. lugdunensis, a potentially high-pathogenicity organism. 

PMID- 24942797
TI  - Primary tracheal malignant lymphoma detected during a regular checkup in an
      asbestos dust-exposed smoker.
AB  - Primary tracheal malignant lymphoma is a rare disease; only 30 cases have been
      reported to date. A 73-year-old Japanese man with a history of asbestos exposure
      was undergoing biannual chest computed tomography (CT) twice a year as a routine
      procedure for those previously exposed to asbestos. He had been smoking since the
      age of 32. In September 2010, chest CT during this regular checkup revealed a
      polypoid lesion in his trachea and pleural plaques, which were suspected to be
      caused by asbestos. Bronchoscopy performed in October revealed a polypoid lesion
      with granules and nodules in the trachea. A diagnosis of non-Hodgkin lymphoma
      (NHL) and extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid
      tissue (MALT) was confirmed by histological analysis of the biopsy specimens. To
      our knowledge, this is the first case of primary tracheal lymphoma associated
      with a history of asbestos exposure. Several reports have documented no
      correlation between asbestos and malignant lymphoma. In addition, the correlation
      between smoking and NHL is weak. Although we cannot exclude the possibility of a
      simple coincidence of asbestos, smoking, and tracheal lymphoma, this case
      suggests that asbestos and smoking might have multiplicative effects in the
      development or progression of tracheal lymphoma.

PMID- 24942799
TI  - Intratumoral DNA content heterogeneity in breast carcinomas demonstrated by core
      punch tissue sampling and flow cytometry.
AB  - Further to advancements in instrumentation and fluorescent dye technologies,
      there has been a resurgence of interest in the flow cytometric assay of formalin
      fixed, paraffin-embedded specimens. Here we present a novel, simple and effective
      alternative to whole block sectioning that allows selective multisampling of
      tissues within a specimen block and the investigation of intratumoral
      heterogeneity. Formalin-fixed, paraffin-embedded breast carcinoma specimens were
      core-punched using 1.0 mm diameter needles and assayed by flow cytometry using a
      modified Hedley method. Intratumoral heterogeneity for DNA index and per cent S
      phase fraction was detected in 10 of 23 (44%) and 11 of 23 (47%) specimens
      respectively. Macro-level genomic heterogeneity is common in breast cancer even
      within a single surgical specimen block. Studies investigating the relationship
      of DNA content heterogeneity to other markers of genomic instability such as
      mutations, deletions, insertions and translocations are warranted.

PMID- 24942798
TI  - Evidence of reproductive stoppage in families with autism spectrum disorder: a
      large, population-based cohort study.
AB  - IMPORTANCE: Few studies have examined the curtailment of reproduction (ie,
      stoppage) after the diagnosis of a child with autism spectrum disorder (ASD).
      OBJECTIVE: To examine stoppage in a large, population-based cohort of families in
      which a child has received a diagnosis of ASD. DESIGN, SETTING, AND PARTICIPANTS:
      Individuals with ASD born from January 1, 1990, through December 31, 2003, were
      identified in the California Department of Developmental Services records, which
      were then linked to state birth certificates to identify full sibs and half-sibs
      and to obtain information on birth order and demographics. A total of 19,710 case
      families in which the first birth occurred within the study period was
      identified. These families included 39,361 individuals (sibs and half-sibs).
      Control individuals were randomly sampled from birth certificates and matched 2:1
      to cases by sex, birth year, and maternal age, self-reported race/ethnicity, and
      county of birth after removal of children receiving services from the California
      Department of Developmental Services. Using similar linkage methods as for case
      families, 36,215 pure control families (including 75,724 total individuals) were
      identified that had no individuals with an ASD diagnosis. EXPOSURES: History of
      affected children. MAIN OUTCOMES AND MEASURES: Stoppage was investigated by
      comparing the reproductive behaviors of parents after the birth of a child with
      ASD vs an unaffected child using a survival analysis framework for time to next
      birth and adjusting for demographic variables. RESULTS: For the first few years
      after the birth of a child with ASD, the parents' reproductive behavior was
      similar to that of control parents. However, birth rates differed in subsequent
      years; overall, families whose first child had ASD had a second child at a rate
      of 0.668 (95% CI, 0.635-0.701) that of control families, adjusted for birth year,
      birth weight, maternal age, and self-reported maternal race/ethnicity. Results
      were similar when a later-born child was the first affected child in the family.
      Reproductive curtailment was slightly stronger among women who changed partners
      (relative rate for second-born children, 0.553 [95% CI, 0.498-0.614]).
      CONCLUSIONS AND RELEVANCE: These results provide the first quantitative
      assessment and convincing statistical evidence of reproductive stoppage related
      to ASD. These findings have implications for recurrence risk estimation and
      genetic counseling.

PMID- 24942800
TI  - Peritoneal dissemination of a gastric API2-MALT1-positive MALT lymphoma.

PMID- 24942801
TI  - Engaging students with plant science: the Plant Science TREE.

PMID- 24942802
TI  - Patients' preferences for gonadotrophin-releasing hormone analogs in in vitro
      fertilization.
AB  - BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists reduce ovarian
      hyperstimulation syndrome (OHSS) at the price of a small reduction in
      effectiveness compared to GnRH agonists. The aim of this study was to investigate
      patients' preferences on effectiveness, safety and burden of GnRH analogs.
      METHODS: A discrete choice experiment (DCE) and a trade-off question were
      designed. Patients embarking on assisted reproductive technique treatment were
      asked to choose between two hypothetical medications which differed in
      effectiveness, safety and burden. RESULTS: A total of 172 questionnaires were
      analyzed. All attributes of the DCE had a statistically significant impact on the
      preference of the respondents. Respondents were willing to trade off 0.87 and
      0.81% effectiveness for a decrease in OHSS risk and for fewer side effects,
      respectively. Respondents were not willing to trade off effectiveness for
      'importance of compliance' (trade-off 0.40%) or a shorter 'duration of treatment'
      (trade-off 0.26%). The trade-off questions showed that already at a 2.0% increase
      in pregnancy rate in favor of the agonists, the majority of the respondents
      changed their preference from antagonists to agonists (2.0%, 95% CI 1.7-2.1).
      CONCLUSION: Safety and burden are important to patients, but are not important
      enough to make up for a small decrease in pregnancy rate.

PMID- 24942803
TI  - Natural or deliberate outbreak in Pakistan: how to prevent or detect and trace
      its origin: biosecurity, surveillance, forensics.
AB  - Over the last few decades biosecurity and biosafety have emerged as a prominent
      public health concern due to some high-profile accidents. Effective strategies to
      deal with the outbreak, whether deliberate or non-deliberate requires a
      multidisciplinary approach and coordinated decision-making by various state
      departments such as health, forensics, agriculture, environment, intelligence,
      law and enforcement, etc. In a dynamic global environment and the overwhelming
      asymmetric threats from the non-state actors, it is of utmost importance to
      understand the biosecurity issues and initiate a coordinated global effort to
      cope with biosecurity and biosafety breaches and develop an as effective response
      mechanism. An attractive choice for the terrorists, state enemies and non-state
      actors is the use of biological weapons. An unwanted incident may not only bring
      chaos to the people, but also can inflict severe economic damage industrially and
      locally as was in the notorious foot-and-mouth disease outbreak. Because of
      special geopolitical compulsion, Pakistan is one of the hot spots where special
      action needs to be taken. The current review focuses on the various approaches,
      technologies that can be used to alleviate the chances of biosafety and
      biosecurity incident and emphasizes the role of modern technology that can be
      used in this regard. 

PMID- 24942805
TI  - Berberine-induced tumor suppressor p53 up-regulation gets involved in the
      regulatory network of MIR-23a in hepatocellular carcinoma.
AB  - AIM OF THE STUDY: To investigate the involvement of p53 in the regulatory network
      of microRNA-23a (miR-23a) in berberine-treated hepatocellular carcinoma (HCC)
      cells. METHODS: The biogenesis of miR-23a upon berberine treatment was monitored
      by detecting the transcript expression of primary precursor, precursor and mature
      forms of miR-23a. Protein expression was detected with immunoblotting. The
      binding capacity between p53 and chromatin DNA was determined by chromatin
      immunoprecipitation. The role of miR-23a in mediating suppression of HCC by
      berberine was determined both in vitro and in vivo. RESULTS: miR-23a was up
      regulated upon berberine treatment in human HCC cells, and berberine could
      increase the expression of primary precursor, precursor and mature forms of miR
      23a. The up-regulation of miR-23a by berberine is p53-dependent. Inhibition of
      p53 expression and activity could block the up-regulation of miR-23a induced by
      berberine. Furthermore, berberine-induced miR-23a expression may mediate the
      transcription activation of p53-related tumor suppressive genes p21 and
      GADD45alpha. Inhibition of miR-23a abolishes the binding of p53 onto chromatin
      and attenuates transcription activation of p21 and GADD45alpha. Target prediction
      and experimental validation demonstrate that berberine-induced miR-23a may target
      to Nek6 to suppress its expression. Berberine-induced G2/M cell cycle arrest in
      HCC was attenuated when miR-23a was inhibited. Berberine-induced cell death and
      in vivo tumor growth inhibition are attenuated upon inhibition of miR-23a.
      CONCLUSION: Our study reveals that miR-23a may be involved in regulating the anti
      HCC effect of berberine by mediating the regulation of p53.

PMID- 24942804
TI  - The epigenome of Trypanosoma brucei: a regulatory interface to an unconventional
      transcriptional machine.
AB  - The epigenome represents a major regulatory interface to the eukaryotic genome.
      Nucleosome positions, histone variants, histone modifications and chromatin
      associated proteins all play a role in the epigenetic regulation of DNA function.
      Trypanosomes, an ancient branch of the eukaryotic evolutionary lineage, exhibit
      some highly unusual transcriptional features, including the arrangement of
      functionally unrelated genes in large, polymerase II transcribed polycistronic
      transcription units, often exceeding hundreds of kilobases in size. It is
      generally believed that transcription initiation plays a minor role in regulating
      the transcript level of genes in trypanosomes, which are mainly regulated post
      transcriptionally. Recent advances have revealed that epigenetic mechanisms play
      an essential role in the transcriptional regulation of Trypanosoma brucei. This
      suggested that the modulation of gene activity, particularly that of pol I
      transcribed genes, is, indeed, an important control mechanism, and that the
      epigenome is critical in regulating gene expression programs that allow the
      successful migration of this parasite between hosts, as well as the continuous
      evasion of the immune system in mammalian hosts. A wide range of epigenetic
      signals, readers, writers and erasers have been identified in trypanosomes, some
      of which have been mapped to essential genetic functions. Some epigenetic
      mechanisms have also been observed to be unique to trypanosomes. We review recent
      advances in our understanding of epigenetic control mechanisms in T. brucei, the
      causative agent of African sleeping sickness, and highlight the utility of
      epigenetic targets in the possible development of new therapies for human African
      trypanosomiasis. 

PMID- 24942807
TI  - Pandemic clinical case definitions are non-specific: multiple respiratory viruses
      circulating in the early phases of the 2009 influenza pandemic in New South
      Wales, Australia.
AB  - BACKGROUND: During the early phases of the 2009 pandemic, subjects with influenza
      like illness only had laboratory testing specific for the new A(H1N1)pdm09 virus.
      FINDINGS: Between 25th May and 7th June 2009, during the pandemic CONTAIN phase,
      A(H1N1)pdm09 virus was detected using nucleic acid tests in only 56 of 1466
      (3.8%) samples meeting the clinical case definition required for A(H1N1)pdm09
      testing. Two hundred and fifty-five randomly selected A(H1N1)pdm09 virus-negative
      samples were tested for other respiratory viruses using a real-time multiplex PCR
      assay. Of the 255 samples tested, 113 (44.3%) had other respiratory viruses
      detected: rhinoviruses 63.7%, seasonal influenza A 17.6%, respiratory syncytial
      virus 7.9%, human metapneumovirus 5.3%, parainfluenzaviruses 4.4%, influenza B
      virus 4.4%, and enteroviruses 0.8%. Viral co-infections were present in 4.3% of
      samples. CONCLUSIONS: In the very early stages of a new pandemic, limiting
      testing to only the novel virus will miss other clinically important co
      circulating respiratory pathogens.

PMID- 24942806
TI  - Water and sodium in heart failure: a spotlight on congestion.
AB  - Despite all available therapies, the rates of hospitalization and death from
      heart failure (HF) remain unacceptably high. The most common reasons for hospital
      admission are symptoms related to congestion. During hospitalization, most
      patients respond well to standard therapy and are discharged with significantly
      improved symptoms. Post-discharge, many patients receive diligent and frequent
      follow-up. However, rehospitalization rates remain high. One potential
      explanation is a persistent failure by clinicians to adequately manage congestion
      in the outpatient setting. The failure to successfully manage these patients post
      discharge may represent an unmet need to improve the way congestion is both
      recognized and treated. A primary aim of future HF management may be to improve
      clinical surveillance to prevent and manage chronic fluid overload while
      simultaneously maximizing the use of evidence-based therapies with proven long
      term benefit. Improvement in cardiac function is the ultimate goal and
      maintenance of a "dry" clinical profile is important to prevent hospital
      admission and improve prognosis. This paper focuses on methods for monitoring
      congestion, and strategies for water and sodium management in the context of the
      complex interplay between the cardiac and renal systems. A rationale for
      improving recognition and treatment of congestion is also proposed. 

PMID- 24942808
TI  - Reappraisal of the clinical pharmacology of low-dose aspirin by comparing novel
      direct and traditional indirect biomarkers of drug action.
AB  - BACKGROUND: Even though the acetylation of platelet cyclooxygenase (COX)-1 at
      serine-529 is the direct mechanism of action of low-dose aspirin, its
      antiplatelet effect has been characterized using indirect indexes of COX-1
      activity. OBJECTIVES: We performed a clinical study with enteric-coated low-dose
      aspirin (EC-aspirin), in healthy subjects, to evaluate the effects on the extent
      and duration of platelet COX-1 acetylation, using a novel proteomic strategy for
      absolute protein quantification (termed AQUA), as compared with traditional
      pharmacokinetic and pharmacodynamic parameters. SUBJECTS AND METHODS: In a phase
      I, single-arm, open-label study of EC aspirin (100 mg day(-1) ) administered to
      24 healthy subjects, we compared, over a 24 h-period on day 1 and 7, % platelet
      acetylated COX-1 (AceCOX-1) with traditional pharmacokinetic and pharmacodynamics
      [i.e. serum thromboxane (TX) B2 , platelet function by monitoring
      CEPI(collagen/epinephrine) closure time (CT) using whole-blood PFA-100 and
      urinary excretion of 11-dehydro-TXB2 ] parameters. RESULTS: Acetylation of
      platelet COX-1 was measurable before detection of aspirin levels in the systemic
      circulation and increased in a cumulative fashion upon repeated dosing. After the
      last dose of EC-aspirin, %AceCOX-1, serum TXB2 and CEPI-CT values were maximally
      and persistently modified throughout 24 h; they averaged 76 +/- 2%, 99.0 +/- 0.4%
      and 271 +/- 5 s, respectively. EC-aspirin caused 75% reduction in urinary 11
      dehydro-TXB2 excretion. After chronic dosing with aspirin, the pharmacokinetics
      of acetylsalicylic acid was completely dissociated from pharmacodynamics.
      CONCLUSIONS: The demonstrated feasibility of quantifying the extent and duration
      of platelet COX-1 acetylation will allow characterizing the genetic,
      pharmacokinetic and pharmacodynamic determinants of the inter-individual
      variability in the antiplatelet response to low-dose aspirin as well as
      identifying extra-platelet sites of drug action.

PMID- 24942809
TI  - GIL, a new c-di-GMP-binding protein domain involved in regulation of cellulose
      synthesis in enterobacteria.
AB  - In contrast to numerous enzymes involved in c-di-GMP synthesis and degradation in
      enterobacteria, only a handful of c-di-GMP receptors/effectors have been
      identified. In search of new c-di-GMP receptors, we screened the Escherichia coli
      ASKA overexpression gene library using the Differential Radial Capillary Action
      of Ligand Assay (DRaCALA) with fluorescently and radioisotope-labelled c-di-GMP.
      We uncovered three new candidate c-di-GMP receptors in E. coli and characterized
      one of them, BcsE. The bcsE gene is encoded in cellulose synthase operons in
      representatives of Gammaproteobacteria and Betaproteobacteria. The purified BcsE
      proteins from E. coli, Salmonella enterica and Klebsiella pneumoniae bind c-di
      GMP via the domain of unknown function, DUF2819, which is hereby designated GIL,
      GGDEF I-site like domain. The RxGD motif of the GIL domain is required for c-di
      GMP binding, similar to the c-di-GMP-binding I-site of the diguanylate cyclase
      GGDEF domain. Thus, GIL is the second protein domain, after PilZ, dedicated to c
      di-GMP-binding. We show that in S. enterica, BcsE is not essential for cellulose
      synthesis but is required for maximal cellulose production, and that c-di-GMP
      binding is critical for BcsE function. It appears that cellulose production in
      enterobacteria is controlled by a two-tiered c-di-GMP-dependent system involving
      BcsE and the PilZ domain containing glycosyltransferase BcsA. 

PMID- 24942810
TI  - A review of contemporary work on the ethics of ambient assisted living
      technologies for people with dementia.
AB  - Ambient assisted living (AAL) technologies can provide assistance and support to
      persons with dementia. They might allow them the possibility of living at home
      for longer whilst maintaining their comfort and security as well as offering a
      way towards reducing the huge economic and personal costs forecast as the
      incidence of dementia increases worldwide over coming decades. However, the
      development, introduction and use of AAL technologies also trigger serious
      ethical issues. This paper is a systematic literature review of the on-going
      scholarly debate about these issues. More specifically, we look at the ethical
      issues involved in research and development, clinical experimentation, and
      clinical application of AAL technologies for people with dementia and related
      stakeholders. In the discussion we focus on: (1) the value of the goals of AAL
      technologies, (2) the special vulnerability of persons with dementia in their
      private homes, (3) the complex question of informed consent for the usage of AAL
      technologies. 

PMID- 24942812
TI  - Nurses' attitudes towards older people and working with older patients: an
      explanatory model.
AB  - AIM: To establish an explanatory model of registered nurses' attitudes towards
      older people and working with older patients. BACKGROUND: Increasing demands for
      health-care from an ageing population will require a higher proportion of nurses
      who have positive attitudes towards older people and like working with older
      patients. METHOD: A convenience sample of registered nurses (n = 579; 79.3%
      response rate) attending continuing professional education courses within a large
      university in London was surveyed from October to December 2011. RESULTS:
      Registered nurses expressed positive attitudes towards older people and 89.7%
      reported positive attitudes towards working with older patients. The variables of
      self-ageing anxiety, attitudes towards health-care resource allocation, knowledge
      of ageing, ethnic group, job title, attitudes towards older patients and
      interaction between ethnic group and attitudes towards working with older
      patients explained 42.6% of the variance in attitudes towards older people.
      Factors, including attitudes towards older people, self-ageing anxiety,
      commitment to nursing, attitudes towards health-care resources allocation among
      older people and clinical specialty explained 16.7-34.3% of the variance in
      attitudes towards older patients. CONCLUSION: The models identified several
      related factors that may help in the selection and management of nurses for
      caring older people. IMPLICATIONS FOR NURSING MANAGEMENT: Our findings highlight
      the importance of investing in continuing education related to gerontological
      nursing and the ageing process so that there is a growing pool of registered
      nurses who wish to care for older patients.

PMID- 24942813
TI  - First adaptation of coping power program as a classroom-based prevention
      intervention on aggressive behaviors among elementary school children.
AB  - Children with high levels of aggressive behavior create a major management
      problem in school settings and interfere with the learning environment of their
      classmates. We report results from a group-randomized trial of a program aimed at
      preventing aggressive behaviors. The purpose of the current study, therefore, was
      to determine the extent to which an indicated prevention program, Coping Power
      Program, is capable of reducing behavioral problems and improving pro-social
      behavior when delivered as a universal classroom-based prevention intervention.
      Nine classes (five first grade and four second grade) were randomly assigned to
      intervention or control conditions. Findings showed a significant reduction in
      overall problematic behaviors and in inattention-hyperactivity problems for the
      intervention classes compared to the control classes. Students who received
      Coping Power Program intervention also showed more pro-social behaviors at
      postintervention. The implications of these findings for the implementation of
      strategies aimed at preventing aggressive behavior in school settings are
      discussed. 

PMID- 24942814
TI  - Climate warming and agricultural stressors interact to determine stream
      periphyton community composition.
AB  - Lack of knowledge about how the various drivers of global climate change will
      interact with multiple stressors already affecting ecosystems is the basis for
      great uncertainty in projections of future biological change. Despite concerns
      about the impacts of changes in land use, eutrophication and climate warming in
      running waters, the interactive effects of these stressors on stream periphyton
      are largely unknown. We manipulated nutrients (simulating agricultural runoff),
      deposited fine sediment (simulating agricultural erosion) (two levels each) and
      water temperature (eight levels, 0-6  degrees C above ambient) simultaneously in
      128 streamside mesocosms. Our aim was to determine the individual and combined
      effects of the three stressors on the algal and bacterial constituents of the
      periphyton. All three stressors had pervasive individual effects, but in
      combination frequently produced synergisms at the population level and
      antagonisms at the community level. Depending on sediment and nutrient
      conditions, the effect of raised temperature frequently produced contrasting
      response patterns, with stronger or opposing effects when one or both stressors
      were augmented. Thus, warming tended to interact negatively with nutrients or
      sediment by weakening or reversing positive temperature effects or strengthening
      negative ones. Five classes of algal growth morphology were all affected in
      complex ways by raised temperature, suggesting that these measures may prove
      unreliable in biomonitoring programs in a warming climate. The evenness and
      diversity of the most abundant bacterial taxa increased with temperature at
      ambient but not with enriched nutrient levels, indicating that warming coupled
      with nutrient limitation may lead to a more evenly distributed bacterial
      community as temperatures rise. Freshwater management decisions that seek to
      avoid or mitigate the negative effects of agricultural land use on stream
      periphyton should be informed by knowledge of the interactive effects of multiple
      stressors in a warming climate. 

PMID- 24942811
TI  - Clinical application of growth factors and cytokines in wound healing.
AB  - Wound healing is a complex and dynamic biological process that involves the
      coordinated efforts of multiple cell types and is executed and regulated by
      numerous growth factors and cytokines. There has been a drive in the past two
      decades to study the therapeutic effects of various growth factors in the
      clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous
      ulcers, diabetic foot ulcers). For this review, we conducted an online search of
      Medline/PubMed and critically analyzed the literature regarding the role of
      growth factors and cytokines in the management of these wounds. We focused on
      currently approved therapies, emerging therapies, and future research
      possibilities. In this review, we discuss four growth factors and cytokines
      currently being used on and off label for the healing of wounds. These include
      granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor,
      vascular endothelial growth factor, and basic fibroblast growth factor. While the
      clinical results of using growth factors and cytokines are encouraging, many
      studies involved a small sample size and are disparate in measured endpoints.
      Therefore, further research is required to provide definitive evidence of
      efficacy. 

PMID- 24942816
TI  - In(OTf)3-catalysed one-pot versatile pyrrole synthesis through domino annulation
      of alpha-oxoketene-N,S-acetals with nitroolefins.
AB  - In(OTf)3-catalyzed robust and sustainable one-pot access to previously unknown
      and synthetically demanding polysubstituted pyrroles via [3 + 2] annulation of
      alpha-oxoketene-N,S-acetals with beta-nitrostyrenes has been achieved under
      solvent-free conditions. The merit of this domino Michael addition/cyclization
      sequence is highlighted by its operational simplicity, short reaction time (5-10
      min), good to excellent yields, tolerance of a large variety of functional
      groups, and efficiency of producing two new (C-C and C-N) bonds and one highly
      functionalized pyrrole ring in a single operation, which make it an ideal
      alternative to existing methods. 

PMID- 24942815
TI  - Prostate cancer xenografts engineered from 3D precision-porous poly(2
      hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy
      escape.
AB  - Synthetic biomaterial scaffolds show promise for in vitro and in vivo 3D cancer
      models. Tumors engineered in biomaterial scaffolds have shown evidence of being
      more physiologically relevant than some traditional preclinical model systems,
      and synthetic biomaterials provide the added benefit of defined and consistent
      microenvironmental control. Here, we examine sphere-templated poly(2-hydroxyethyl
      methacrylate) (pHEMA) scaffolds as the basis for engineering xenografts from
      multiple human prostate cancer cell lines. pHEMA scaffolds seeded and pre
      cultured with tumorigenic M12 cells prior to implantation generated tumors in
      athymic nude mice, demonstrating the ability of the scaffolds to be used as a
      synthetic vehicle for xenograft generation. pHEMA scaffolds seeded with LNCaP C4
      2 cells, which require Matrigel or stromal cell support for tumor formation, were
      poorly tumorigenic up to 12 weeks after implantation even when Matrigel was
      infused into the scaffold, demonstrating a lack of necessary pro-tumorigenic
      signaling within the scaffolds. Finally, M12mac25 cells, which are ordinarily
      rendered non-tumorigenic through the expression of the tumor suppressor insulin
      like growth factor binding protein 7 (IGFBP7), displayed a tumorigenic response
      when implanted within porous pHEMA scaffolds. These M12mac25 tumors showed
      significant macrophage infiltration within the scaffolds driven by the foreign
      body response to the materials. These findings show the potential for this
      biomaterials-based model system to be used in the study of prostate cancer
      tumorigenesis and dormancy escape. 

PMID- 24942817
TI  - Long-term stability of a vaccine formulated with the amphipol-trapped major outer
      membrane protein from Chlamydia trachomatis.
AB  - Chlamydia trachomatis is a major bacterial pathogen throughout the world.
      Although antibiotic therapy can be implemented in the case of early detection, a
      majority of the infections are asymptomatic, requiring the development of
      preventive measures. Efforts have focused on the production of a vaccine using
      the C. trachomatis major outer membrane protein (MOMP). MOMP is purified in its
      native (n) trimeric form using the zwitterionic detergent Z3-14, but its
      stability in detergent solutions is limited. Amphipols (APols) are synthetic
      polymers that can stabilize membrane proteins (MPs) in detergent-free aqueous
      solutions. Preservation of protein structure and optimization of exposure of the
      most effective antigenic regions can avoid vaccination with misfolded, poorly
      protective protein. Previously, we showed that APols maintain nMOMP secondary
      structure and that nMOMP/APol vaccine formulations elicit better protection than
      formulations using either recombinant or nMOMP solubilized in Z3-14. To achieve a
      greater understanding of the structural behavior and stability of nMOMP in APols,
      we have used several spectroscopic techniques to characterize its secondary
      structure (circular dichroism), tertiary and quaternary structures
      (immunochemistry and gel electrophoresis) and aggregation state (light
      scattering) as a function of temperature and time. We have also recorded NMR
      spectra of (15)N-labeled nMOMP and find that the exposed loops are detectable in
      APols but not in detergent. Our analyses show that APols protect nMOMP much
      better than Z3-14 against denaturation due to continuous heating, repeated
      freeze/thaw cycles, or extended storage at room temperature. These results
      indicate that APols can help improve MP-based vaccine formulations.

PMID- 24942819
TI  - A mediator effect size in randomized clinical trials.
AB  - To understand the process by which a treatment (T) achieves an effect on outcome
      (O) and thus to improve the effect of T on O, it is vital to detect mediators, to
      compare the impact of different mediators, and to develop hypotheses about the
      causal factors (all mediators) linking T and O. An index is needed to facilitate
      interpretation of the potential clinical importance of a mediator (M) of choice
      of T on treatment O in randomized clinical trials (RCTs). Ideally such a mediator
      effect size should (1) be invariant under any rescaling of M and O consistent
      with the model used, and (2) reflect the difference between the overall observed
      effect of T on O and what the maximal effect of T on O could be were the
      association between T and M broken. A mediator effect size is derived first for
      the traditional linear model, and then more generally for any categorical
      (ordered or non-ordered) potential mediator. Issues such as the problem of
      multiple treatments, outcomes and mediators, and of causal inferences, and the
      correspondence between this approach and earlier ones, are discussed.
      Illustrations are given of the application of the approach.

PMID- 24942818
TI  - Solution behavior and crystallization of cytochrome bc1 in the presence of
      amphipols.
AB  - Detergents classically are used to keep membrane proteins soluble in aqueous
      solutions, but they tend to destabilize them. This problem can be largely
      alleviated thanks to the use of amphipols (APols), small amphipathic polymers
      designed to substitute for detergents. APols adsorb at the surface of the
      transmembrane region of membrane proteins, keeping them water-soluble while
      stabilizing them bio-chemically. Membrane protein/APol complexes have proven,
      however, difficult to crystallize. In this study, the composition and solution
      properties of complexes formed between mitochondrial cytochrome bc1 and A8-35,
      the most extensively used APol to date, have been studied by means of size
      exclusion chromatography, sucrose gradient sedimentation, and small-angle neutron
      scattering. Stable, monodisperse preparations of bc1/A8-35 complexes can be
      obtained, which, depending on the medium, undergo either repulsive or attractive
      interactions. Under crystallization conditions, diffracting three-dimensional
      crystals of A8-35-stabilized cytochrome bc1 formed, but only in the concomitant
      presence of APol and detergent.

PMID- 24942820
TI  - Health service barriers to HIV testing and counseling among pregnant women
      attending Antenatal Clinic; a cross-sectional study.
AB  - BACKGROUND: HIV testing and counseling (HTC) remains critical in the global
      efforts to reach a goal of universal access to prevention and timely human
      immunodeficiency virus (HIV) treatment and health care. Routine HIV testing has
      been shown to be cost-effective and life-saving by prolonging the life expectancy
      of HIV patients and reducing the annual HIV transmission rate. However, these
      benefits of routine HIV testing may not be seen among pregnant women attending
      antenatal clinic (ANC) due to health facility related factors. This paper
      presents the influence of health facility related factors on HTC to inform HTC
      implementation. METHODS: The study was cross-sectional in design and used
      structured questionnaire and interview guides to gather information from 300
      pregnant women aged 18 to 49 years and had attended ANC for more than twice at
      the time of the study. Twelve health workers were interviewed as key informants.
      Respondents were selected from the five sub metro health facilities in the Kumasi
      Metropolis through systematic random sampling from August to November 2011.
      Pregnant women who had not tested after two or more ANC visits were classified as
      not utilizing HTC. Data was analyzed with STATA 11. Logistic regression was run
      to assess the odds ratios at 95% confidence level. RESULTS: Twenty-four percent
      of the pregnant women had not undergone HTC, with "never been told" emerging as
      the most cited reason as reported by 29.5% of respondents. Decisions by pregnant
      women to take up HTC were mostly influenced by factors such as lack of
      information, perceptions of privacy and confidentiality, waiting time, poor
      relationship with health staff and fear of being positive. CONCLUSIONS: Access to
      HTC health facility alone does not translate into utilization of HTC service.
      Improving health facility related factors such as health education and
      information, confidentiality, health staff turnaround time and health staff
      client relationship related to HTC will improve implementation.

PMID- 24942821
TI  - A competitive chemiluminescence enzyme immunoassay method for beta-defensin-2
      detection in transgenic mice.
AB  - A competitive chemiluminescence enzyme immunoassay (CLEIA) method for porcine
      beta-defensin-2 (pBD-2) detection in transgenic mice was established. Several
      factors that affect detection, including luminol, p-iodophenol and hydrogen
      peroxide concentrations, as well as pH, were studied and optimized. The linear
      range of the proposed method for pBD-2 detection under optimal conditions was
      0.05-80 ng/mL with a correlation coefficient of 0.9960. Eleven detections of a 30
      ng/mL pBD-2 standard sample were performed. Reproducible results were obtained
      with a relative standard deviation of 3.94%. The limit of detection of the method
      for pBD-2 was 3.5 pg/mL (3sigma). The proposed method was applied to determine
      pBD-2 expression levels in the tissues of pBD-2 transgenic mice, and compared
      with LC-MS/MS and quantitative real-time reverse-transcriptase polymerase chain
      reaction. This suggests that the CLEIA can be used as a valuable method to detect
      and quantify pBD-2.

PMID- 24942822
TI  - A grey literature review of special events for promoting cancer screenings.
AB  - BACKGROUND: Cancer remains the second leading cause of mortality in the United
      States. Special events such as health fairs, screening days or cultural festivals
      are employed often for community education about cancer screening. A previous
      systematic review of the published literature was conducted in 2012-2013. The
      purpose of this study was to conduct a grey literature component of special
      events that promote breast, cervical and colorectal cancer screening in the U.S.
      METHODS: We conducted a grey literature search of dissertations/theses and
      conference abstracts. The theses/dissertations were restricted to those: 1)
      written in English, 2) published from January 1990 to December 2011, 3) examined
      at least one of the predefined categories of special events, 4) involved cancer
      screening for breast, cervical, and/or colorectal cancer, 5) included outcome
      data, and 6) conducted in the United States. A review of U.S. public health and
      cancer conference abstracts, that were readily available and had focused on at
      least of 3 cancer types and included outcome data, was conducted. Data were
      abstracted on the purpose, location, primary audience(s), activities conducted,
      screening provided onsite or referrals, and evaluation results. RESULTS: The grey
      literature review found 6 special events. The types of events found added to the
      numbers found in the systematic review, especially receptions or parties and
      cultural festivals/events. All focused on increasing breast and cervical cancer
      screening except one that focused on breast cancer only. The reach of these
      events was targeted at mostly minorities or underserved communities. Common
      evidence-based strategies were group education, small media, and reducing
      structural barriers. Group education involved presentations from physicians, lay
      health advisors, or cancer survivors, while reducing structural barriers included
      activities such as providing screening appointment sign-ups at the event or
      providing transportation for event participants. Mammogram screening rates ranged
      from 6.8% to 60% and Pap tests from 52% to 70%. CONCLUSIONS: Further evaluation
      of special events to promote cancer screening will prove their effectiveness. A
      grey literature review can augment a systematic review of published literature.
      Additional data about these events through the grey literature offered additional
      insights into the goals, intervention components and outcomes of interventions.

PMID- 24942823
TI  - Protein functionalization revised: N-tert-butoxycarbonylation as an elegant tool
      to circumvent protein crosslinking.
AB  - The protection of primary amines available in proteins holds great potential to
      introduce a plethora of diverse functionalities along the protein backbone (e.g.,
      via its carboxylic acid or alcohol moieties) while circumventing the crosslinking
      issue using conventional approaches. This paper reports on a straightforward and
      efficient proof-of-concept including the chemoselective N-tert
      butyloxycarbonylation of the primary amines in the protein gelatin (gel-NH-BOC),
      followed by introducing crosslinkable methacrylamide moieties. The reaction is
      performed successfully under relatively mild conditions (50  degrees C).
      Following selective protein functionalization, the deprotection is realized by
      adding a catalytic amount of an aqueous hydrogen chloride solution. The present
      communication illustrates the occurrence of a straightforward and selective
      deprotection procedure, which is typically required to circumvent the occurrence
      of acidic hydrolysis of the protein backbone. The results hold promise for a
      large range of biomedical applications in which the presence of primary amines is
      essential for preserving the biological activity. 

PMID- 24942824
TI  - Editorial comment to Early effect of dutasteride added to alpha-1 blocker therapy
      for patients with lower urinary tract symptoms associated with benign prostatic
      hyperplasia.

PMID- 24942825
TI  - Effect of molecular orientation angle of imidazolium ring on frictional
      properties of imidazolium-based ionic liquid.
AB  - Ionic liquids have significant potential as lubricants, and it is known that
      ionic liquids exhibit characteristic behavior at solid-liquid interfaces.
      Although it is believed that the structure of ionic liquids at the interface
      contributes to the tribological properties in the region of boundary-mixed
      lubrication, this contribution has not been clarified because such analysis is
      difficult. In this research, we clarify the lubrication mechanism of an
      imidazolium-based ionic liquid by comparing the results of friction tests with
      interfacial molecular orientation analysis using sum frequency generation
      spectroscopy. Consequently, we clarify that the tilt angle of the imidazolium
      ring affects the friction coefficient of the ionic liquid; that is, the larger
      tilt angle, the lower the friction coefficient. 

PMID- 24942826
TI  - Sildenafil reduces ischemia-reperfusion injury in rat ovary: biochemical and
      histopathological evaluation.
AB  - BACKGROUND/AIMS: To evaluate the effects of sildenafil on antioxidant enzyme
      activities, lipid peroxidation and histopathological changes in ovarian tissue
      after ischemia-reperfusion (I/R) injury in a rat model. METHODS: A total of 18
      adult female Wistar albino rats weighing 200-250 g were studied as follows: (1)
      control group: sham operation, (2) I/R group: 3 h of reperfusion after 3 h of
      ischemia and (3) I/R + sildenafil group: 3 h of reperfusion after 3 h of
      ischemia; half an hour before reperfusion, sildenafil (1.4 mg.kg(-1)) was given
      by oral gavage. At the end of the reperfusion periods, the ovarian tissues were
      removed for histopathological examination and to determine malondialdehyde (MDA)
      levels and glutathione peroxidase, myeloperoxidase (MPO) and superoxide dismutase
      (SOD) activities. RESULTS: The I/R group had higher ovarian tissue MDA levels
      than the control group and the IR + sildenafil group (p = 0.016 and p = 0.044,
      respectively). MPO activity was lower in the IR + sildenafil group compared with
      the I/R group (p = 0.022). SOD activity was lower in the I/R group compared with
      the control group and the I/R + sildenafil group (p = 0.030 and p = 0.015,
      respectively). The I/R + sildenafil group had improved histological appearance
      which was not different to the control group (p > 0.05). CONCLUSION: The
      biochemical and histopathological results of this experimental study demonstrated
      that I/R injury in the ovary is ameliorated by sildenafil treatment.

PMID- 24942828
TI  - Guidelines for the diagnosis and treatment of cobalamin and folate disorders.
AB  - The clinical picture is the most important factor in assessing the significance
      of test results assessing cobalamin status because there is no 'gold standard'
      test to define deficiency. Serum cobalamin currently remains the first-line test,
      with additional second-line plasma methylmalonic acid to help clarify
      uncertainties of underlying biochemical/functional deficiencies. Serum
      holotranscobalamin has the potential as a first-line test, but an indeterminate
      'grey area' may still exist. Plasma homocysteine may be helpful as a second-line
      test, but is less specific than methylmalonic acid. The availability of these
      second-line tests is currently limited. Definitive cut-off points to define
      clinical and subclinical deficiency states are not possible, given the variety of
      methodologies used and technical issues, and local reference ranges should be
      established. In the presence of discordance between the test result and strong
      clinical features of deficiency, treatment should not be delayed to avoid
      neurological impairment. Treatment of cobalamin deficiency is recommended in line
      with the British National Formulary. Oral therapy may be suitable and acceptable
      provided appropriate doses are taken and compliance is not an issue. Serum folate
      offers equivalent diagnostic capability to red cell folate and is the first-line
      test of choice to assess folate status. 

PMID- 24942829
TI  - Communicating the harmful effects of medicines.

PMID- 24942827
TI  - The use of non-narcotic pain medication in pediatric gastroenterology.
AB  - The perception of pain in children is easily influenced by environmental factors
      and psychological comorbidities that are known to play an important role in its
      origin and response to therapy. Chronic abdominal pain is one of the most
      commonly treated conditions in modern pediatric gastroenterology and is the
      hallmark of 'functional' disorders that include irritable bowel syndrome,
      functional dyspepsia, and functional abdominal pain. The development of
      pharmacological therapies for these disorders in adults and children has been
      limited by the lack of understanding of the putative, pathophysiological
      mechanisms that underlie them. Peripheral and central pain-signaling mechanisms
      are known to be involved in chronic pain originating from the gastrointestinal
      tract, but few therapies have been developed to target specific pathways or
      enhance correction of the underlying pathophysiology. The responses to therapy
      have been variable, potentially reflecting the heterogeneity of the disorders for
      which they are used. Only a few small, randomized clinical trials have evaluated
      the benefit of pain medications for chronic abdominal pain in children and thus,
      the decision on the most appropriate treatment is often based on adult studies
      and empirical data. This review discusses the most common, non-narcotic
      pharmacological treatments for chronic abdominal pain in children and includes a
      thorough review of the literature to support or refute their use. Because of the
      dearth of pediatric studies, the focus is on pharmacological and alternative
      therapies where there is sufficient evidence of benefit in either adults or
      children with chronic abdominal pain. 

PMID- 24942831
TI  - Creutzfeldt-Jakob disease secondary to dural graft performed in 1988.

PMID- 24942830
TI  - Two cases of Buruli ulcer in Japanese brothers.

PMID- 24942832
TI  - Self-care and Subjectivity among Mexican Diabetes Patients in the United States.
AB  - Type 2 diabetes is considered a public health crisis, particularly among people
      of Mexican descent in the United States. Clinical approaches to diabetes
      management increasingly emphasize self-care, which places responsibility for
      illness on individuals and mandates self-regulation. Using narrative and free
      list data from a two-phase study of low-income first- and second-generation
      Mexican immigrants living with diabetes, we present evidence that self-care among
      our participants involves emotion regulation as well as maintenance of and care
      for family. These findings suggest, in turn, that the ideology of selfhood on
      which these practices are based does not correspond with the ideology of selfhood
      cultivated in the U.S. clinical sphere. Divergence between these ideologies may
      lead to self-conflict for patients and the experience of moral blame. We argue
      that our participants use their explanations of diabetes causality and control as
      a form of self-making, which both resists such blame and asserts an alternative
      form of selfhood that may align more closely with the values held by our Mexican
      American participants. 

PMID- 24942834
TI  - Improving the care of lesbian, bisexual, and transgender populations.

PMID- 24942833
TI  - N-terminal pro-brain natriuretic peptide and cognitive decline in older adults at
      high cardiovascular risk.
AB  - OBJECTIVE: Elevated levels of N-terminal pro-brain natriuretic peptide (NT
      proBNP) are associated with cognitive impairment, which might be explained by
      cardiovascular diseases or risk factors. The aim of this study was to investigate
      the association of NT-proBNP with cognitive function and decline in older adults
      at high risk of cardiovascular disease. METHODS: We studied 5,205 men and women
      (mean age = 75 years) who were recruited into the PROspective Study of
      Pravastatin in the Elderly at Risk. All participants had pre-existing
      cardiovascular disease or risk factors thereof. Four domains of cognitive
      function were tested at baseline and repeated during a follow-up period of 3.2
      years. RESULTS: Participants with higher NT-proBNP (>=450ng/l) had worse baseline
      cognitive function, including reaction time (mean difference high vs low group =
      3.07 seconds, 95% confidence interval [CI] = 0.83 to 5.32), processing speed (
      1.02 digits coded, 95% CI = -1.65 to -0.39), and immediate memory (-0.13 pictures
      remembered, 95% CI = -0.29 to 0.04). There was no significant difference in
      delayed memory (-0.14, 95% CI = -0.38 to 0.10) between the NT-proBNP groups.
      Participants with higher NT-proBNP had a steeper cognitive decline, including
      reaction time (mean annual change high vs low group = 0.60 seconds, 95% CI = 0.14
      to 1.07), processing speed (-0.15 digits coded, 95% CI = -0.25 to -0.05),
      immediate memory (-0.05 pictures remembered, 95% CI = -0.09 to 0.00), and delayed
      memory (-0.05 pictures remembered, 95% CI = -0.11 to 0.01). Associations were
      independent of cardiovascular diseases and risks. INTERPRETATION: Higher NT
      proBNP associates with worse cognitive function and steeper cognitive decline,
      independent of cardiovascular diseases and risks. Further studies to unravel the
      underlying mechanisms are warranted.

PMID- 24942835
TI  - X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and
      insights into its catalytic mechanism.
AB  - Phospholipids have major roles in the structure and function of all cell
      membranes. Most integral membrane proteins from the large CDP-alcohol
      phosphatidyltransferase family are involved in phospholipid biosynthesis across
      the three domains of life. They share a conserved sequence pattern and catalyse
      the displacement of CMP from a CDP-alcohol by a second alcohol. Here we report
      the crystal structure of a bifunctional enzyme comprising a cytoplasmic
      nucleotidyltransferase domain (IPCT) fused with a membrane CDP-alcohol
      phosphotransferase domain (DIPPS) at 2.65 A resolution. The bifunctional protein
      dimerizes through the DIPPS domains, each comprising six transmembrane alpha
      helices. The active site cavity is hydrophilic and widely open to the cytoplasm
      with a magnesium ion surrounded by four highly conserved aspartate residues from
      helices TM2 and TM3. We show that magnesium is essential for the enzymatic
      activity and is involved in catalysis. Substrates docking is validated by
      mutagenesis studies, and a structure-based catalytic mechanism is proposed. 

PMID- 24942836
TI  - Design, quality, and quality assurance of solid recovered fuels for the
      substitution of fossil feedstock in the cement industry.
AB  - This paper describes the requirements for the production, quality, and quality
      assurance of solid recovered fuels (SRF) that are increasingly used in the cement
      industry. Different aspects have to be considered before using SRF as an
      alternative fuel. Here, a study on the quality of SRF used in the cement industry
      is presented. This overview is completed by an investigation of type and
      properties of input materials used at waste splitting and SRF production plants
      in Austria. As a simplified classification, SRF can be divided into two classes:
      a fine, high-calorific SRF for the main burner, or coarser SRF material with low
      calorific value for secondary firing systems, such as precombustion chambers or
      similar systems. In the present study, SRFs coming from various sources that fall
      under these two different waste fuel classes are discussed. Both SRFs are
      actually fired in the grey clinker kiln of the Holcim (Slovensko) plant in
      Rohoznik (Slovakia). The fine premium-quality material is used in the main burner
      and the coarse regular-quality material is fed to a FLS Hotdisc combustion
      device. In general, the alternative fuels are used instead of their substituted
      fossil fuels. For this, chemical compositions and other properties of SRF were
      compared to hard coal as one of the most common conventional fuels in Europe.
      This approach allows to compare the heavy metal input from traditional and
      alternative fuels and to comment on the legal requirements on SRF that, at the
      moment, are under development in Europe. 

PMID- 24942837
TI  - Environmental evaluation of the electric and cogenerative configurations for the
      energy recovery of the Turin municipal solid waste incineration plant.
AB  - Given the desirability of reducing fossil fuel consumption, together with the
      increasing production of combustible solid wastes, there is clearly a need for
      waste treatment systems that achieve both volume reduction and energy recovery.
      Direct incineration method is one such system. The aim of this work was to
      analyze the municipal solid waste incineration plant currently under construction
      in the province of Turin (Piedmont, North Italy), especially the potential for
      energy recovery, and the consequent environmental effects. We analyzed two kinds
      of energy recovery: electric energy (electrical configuration) only, and both
      electric and thermal energy (cogenerative configuration), in this case with a
      different connection hypothesis to the district heating network. After we had
      evaluated the potential of the incinerator and considered local demographic,
      energy and urban planning effects, we assumed different possible connections to
      the district heating network. We computed the local and global environmental
      balances based on the characteristics of the flue gas emitted from the stack,
      taking into consideration the emissions avoided by the substituted sources. The
      global-scale results provided relevant information on the carbon dioxide
      emissions parameter. The results on the local scale were used as reference values
      for the implementation of a Gaussian model (Aermod) that allows evaluation of the
      actual concentration of the pollutants released into the atmosphere. The main
      results obtained highlight the high energy efficiency of the combined production
      of heat and electricity, and the opportunity to minimize the environmental impact
      by including cogeneration in a district heating scheme. 

PMID- 24942839
TI  - Mitral annulus displacement measured by two-dimensional speckle tracking imaging
      to assess the left ventricular longitudinal systolic function in coronary heart
      disease.
AB  - AIM: To assess the clinical utility of measuring mitral annulus displacement
      (MAD) by two-dimensional speckle tracking for the rapid evaluation of left
      ventricular longitudinal systolic function in patients with coronary heart
      disease (CHD). METHODS: Left ventricular longitudinal systolic function was
      evaluated by MAD using speckle tracking echocardiography in 30 healthy volunteers
      (controls) as well as in 30 patients with mild, 30 patients with moderate, and 30
      patients with severe CHD. All participants had their apical four-chamber and two
      chamber view echocardiographic images recorded. Left ventricular end-diastolic
      volume, left ventricular end-systolic volume, and left ventricular ejection
      fraction were calculated by the biplane Simpson method. MAD of interventricular
      septum (MADsep), left ventricular lateral wall (MADlat), and the middle point of
      the mitral annulus (MADmid) were measured offline with speckle-tracking
      echocardiography. MADmid% was defined as MADmid divided by left ventricular end
      diastolic diameter. RESULTS: MADmid% was 16.9 +/- 1.9, 11.8 +/- 3.2, 11.8 +/-
      2.9, and 10.3 +/- 3.6, respectively, in controls and in patients with mild,
      moderate, and severe CHD. All MAD indexes were lower in patients with moderate or
      severe CHD than in controls or patients with mild CHD. CONCLUSIONS: MAD is an
      early and rapid index for the assessment of left ventricular longitudinal
      systolic function in patients with different degrees of coronary artery disease.

PMID- 24942840
TI  - So many migraines, so few subspecialists: analysis of the geographic location of
      United Council for Neurologic Subspecialties (UCNS) certified headache
      subspecialists compared to United States headache demographics.
AB  - OBJECTIVE: To evaluate the geographic location of the United Council for
      Neurologic Subspecialties (UCNS)-certified headache subspecialists as compared
      with ratios of expected migraine and chronic migraine populations in the United
      States. BACKGROUND: The UCNS is a professional medical organization that
      accredits fellowship programs and certifies physicians who demonstrate competence
      in various neurologic subspecialties, including headache medicine. There are a
      limited number of UCNS-certified headache subspecialists currently practicing in
      the United States. METHODS: All of the UCNS-certified headache subspecialists
      were geographically located and compared with demographic data about state
      populations obtained from the U.S. Census. The expected migraine and chronic
      migraine populations were calculated for each state based on recently published
      epidemiologic data. Ratios of UCNS-certified headache subspecialists to expected
      migraine and chronic migraine populations were compared for each state. These
      data were then organized by U.S. Census region and division. RESULTS: As of the
      2012 examination cycle, 416 UCNS-certified headache subspecialists are currently
      practicing in the United States. The states with the highest number of headache
      subspecialists include New York, California, Ohio, Texas, Florida, and
      Pennsylvania. Six states have zero headache subspecialists, eight states have one
      headache subspecialist, and five states have two headache subspecialists. As per
      the U.S. Census, the total U.S. population for ages 12 years and older is
      259,908,563. The total expected migraine population (11.79% of the general
      population) for ages 12 years and older is 30,594,362. The total expected chronic
      migraine population (0.91% of the general population) for ages 12 years and older
      is 2,361,397. The states with the best ratios of headache subspecialists to
      expected migraine and chronic migraine populations include the District of
      Columbia, New Hampshire, New York, and Nebraska. Besides states with zero
      headache subspecialists, the states with the worst ratios of headache
      subspecialists to expected migraine and chronic migraine populations include
      Oregon, Mississippi, Arkansas, and Kansas. When organized by U.S. Census regions,
      the Northeast has the best ratios of headache subspecialists to expected migraine
      and chronic migraine populations, while the West has the worst ratios of headache
      subspecialists to expected migraine and chronic migraine populations. In terms of
      U.S. Census divisions, the Middle Atlantic has the best ratios of headache
      subspecialists to expected migraine and chronic migraine populations, while the
      East South Central has the worst ratios of expected migraine and chronic migraine
      populations. CONCLUSIONS: There is a disproportionately small number of UCNS
      certified headache subspecialists compared with the extensive expected migraine
      and chronic migraine populations in the United States. More UCNS-accredited
      fellowship programs and more UCNS-certified headache subspecialists are needed in
      order to ameliorate this disparity.

PMID- 24942842
TI  - Variable-angle locking plate with or without double-tiered subchondral support
      procedure in the treatment of intra-articular distal radius fracture.
AB  - BACKGROUND: Double-tiered subchondral support (DSS) procedure is two-row fixation
      in which proximal screws support the dorsal subchondral bone, whereas distal
      screws support the volar central subchondral bone, using the volar variable-angle
      locking plate to achieve better anatomical reduction. We examined whether DSS
      improves clinical outcome, complication rate, and loss of correction for dorsally
      displaced Arbeitsgemeinschaft fur Osteosynthesefragen (AO) type C3 distal radius
      fractures. MATERIALS AND METHODS: We reviewed dorsally displaced intra-articular
      AO C3-type distal radius fractures treated at our institutions with a variable
      angle volar locking plate. We assessed 49 patients (27 DSS; 22 non-DSS) treated
      with volar locking plates, with a mean age of 59.9 years and average follow-up of
      20.2 months (range 12-56 months). We evaluated differences in functional outcome,
      complication rates, and loss of correction between groups using radiographic
      parameters. RESULT: There were no differences in clinical outcome and
      complications. Final volar tilt and ulnar variance were better maintained in the
      DSS group (P = 0.01 and 0.03). Change in volar tilt of the non-DSS group was more
      than that of the DSS group (P = 0.00). CONCLUSION: Though there were no
      significant differences in clinical outcomes, we identified a significant
      reduction in final volar tilt, ulnar variance, and change in volar tilt. DSS
      procedure is useful to avoid correction loss when treating unstable C3 distal
      radius fractures and thus would reduce posttraumatic arthrosis. LEVEL OF
      EVIDENCE: Level IV.

PMID- 24942841
TI  - Gonad transcriptome analysis of pearl oyster Pinctada margaritifera:
      identification of potential sex differentiation and sex determining genes.
AB  - BACKGROUND: Black pearl farming is based on culture of the blacklip pearl oyster
      Pinctada margaritifera (Mollusca, lophotrochozoa), a protandrous hermaphrodite
      species. At first maturation, all individuals are males. The female sex appears
      progressively from two years old, which represents a limitation for broodstock
      conditioning for aquaculture production. In marine mollusks displaying
      hermaphroditic features, data on sexual determinism and differentiation,
      including the molecular sex determining cascade, are scarce. To increase genomic
      resources and identify the molecular mechanisms whereby gene expression may act
      in the sexual dimorphism of P. margaritifera, we performed gonad transcriptome
      analysis. RESULTS: The gonad transcriptome of P. margaritifera was sequenced from
      several gonadic samples of males and females at different development stages,
      using a Next-Generation-Sequencing method and RNAseq technology. After Illumina
      sequencing, assembly and annotation, we obtained 70,147 contigs of which 62.2%
      shared homologies with existing protein sequences, and 9% showed functional
      annotation with Gene Ontology terms. Differential expression analysis identified
      1,993 differentially expressed contigs between the different categories of
      gonads. Clustering methods of samples revealed that the sex explained most of the
      variation in gonad gene expression. K-means clustering of differentially
      expressed contigs showed 815 and 574 contigs were more expressed in male and
      female gonads, respectively. The analysis of these contigs revealed the presence
      of known specific genes coding for proteins involved in sex determinism and/or
      differentiation, such as dmrt and fem-1 like for males, or foxl2 and vitellogenin
      for females. The specific gene expression profiles of pmarg-fem1-like, pmarg-dmrt
      and pmarg-foxl2 in different reproductive stages (undetermined, sexual inversion
      and regression) suggest that these three genes are potentially involved in the
      sperm-oocyte switch in P. margaritifera. CONCLUSIONS: The study provides a new
      transcriptomic tool to study reproduction in hermaphroditic marine mollusks. It
      identifies sex differentiation and potential sex determining genes in P.
      margaritifera, a protandrous hermaphrodite species.

PMID- 24942843
TI  - Interactions of dietary protein and adiposity measures in relation to subsequent
      changes in body weight and waist circumference.
AB  - OBJECTIVE: To investigate if dietary protein and degree of adiposity interacts in
      relation to change in body weight and waist circumference (WC) in the general
      population. METHODS: In total 22,433 middle-aged individuals with dietary
      assessment at baseline and anthropometry at baseline and at follow-up about 5
      years later were analyzed with multiple linear regression and dietary
      macronutrient substitution models. Interactions between dietary protein and
      baseline body mass index (BMI) and baseline WC adjusted for BMI (WCBMI ) (divided
      in tertiles; nine groups total), were analyzed in relation to changes in body
      weight (BW) and changes WC adjusted for change in BW. RESULTS: Baseline intake of
      protein was not significantly associated with changes in weight or waist
      circumference. Across the nine groups of baseline BMI and WCBMI there were no
      distinct trends in the associations between dietary protein, whether replacing
      carbohydrate or fat, and weight change. However, individuals in the highest
      tertile of baseline BMI (irrespective of baseline WCBMI ) had significantly
      inverse change in waist circumference when protein replaced carbohydrate, but not
      when protein replaced fat. CONCLUSION: Replacing carbohydrate with protein in the
      diet may prevent a relative increase in WC in individuals with a greater BMI.

PMID- 24942844
TI  - Constituting fully integrated visual analysis system for Cu(II) on TiO2/cellulose
      paper.
AB  - As a cheap and abundant porous material, cellulose filter paper was used to
      immobilize nano-TiO2 and denoted as TiO2/cellulose paper (TCP). With high
      adsorption capacity for Cu(II) (more than 1.65 mg), TCP was used as an adsorbent,
      photocatalyst, and colorimetric sensor at the same time. Under the optimum
      adsorption conditions, i.e., pH 6.5 and 25  degrees C, the adsorption ratio of
      Cu(II) was higher than 96.1%. Humic substances from the matrix could be enriched
      onto TCP but the interference of their colors on colorimetric detection could be
      eliminated by the photodegradation. In the presence of hydroxylamine,
      neocuproine, as a selective indicator, was added onto TCP, and a visual color
      change from white to orange was generated. The concentration of Cu(II) was
      quantified by the color intensity images using image processing software. This
      fully integrated visual analysis system was successfully applied for the
      detection of Cu(II) in 10.0 L of drinking water and seawater with a
      preconcentration factor of 10(4). The log-linear calibration curve for Cu(II) was
      in the range of 0.5-50.0 MUg L(-1) with a determination coefficient (R(2)) of
      0.985 and its detection limit was 0.073 MUg L(-1). 

PMID- 24942845
TI  - Evidence for two-dimensional solitary sound waves in a lipid controlled interface
      and its implications for biological signalling.
AB  - Biological membranes by virtue of their elastic properties should be capable of
      propagating localized perturbations analogous to sound waves. However, the
      existence and the possible role of such waves in communication in biology remain
      unexplored. Here, we report the first observations of two-dimensional solitary
      elastic pulses in lipid interfaces, excited mechanically and detected by FRET. We
      demonstrate that the nonlinearity near a maximum in the susceptibility of the
      lipid monolayer results in solitary pulses that also have a threshold for
      excitation. These experiments clearly demonstrate that the state of the interface
      regulates the propagation of pulses both qualitatively and quantitatively.
      Finally, we elaborate on the striking similarity of the observed phenomenon to
      nerve pulse propagation and a thermodynamic basis of cell signalling in general. 

PMID- 24942846
TI  - Controlling free flight of a robotic fly using an onboard vision sensor inspired
      by insect ocelli.
AB  - Scaling a flying robot down to the size of a fly or bee requires advances in
      manufacturing, sensing and control, and will provide insights into mechanisms
      used by their biological counterparts. Controlled flight at this scale has
      previously required external cameras to provide the feedback to regulate the
      continuous corrective manoeuvres necessary to keep the unstable robot from
      tumbling. One stabilization mechanism used by flying insects may be to sense the
      horizon or Sun using the ocelli, a set of three light sensors distinct from the
      compound eyes. Here, we present an ocelli-inspired visual sensor and use it to
      stabilize a fly-sized robot. We propose a feedback controller that applies torque
      in proportion to the angular velocity of the source of light estimated by the
      ocelli. We demonstrate theoretically and empirically that this is sufficient to
      stabilize the robot's upright orientation. This constitutes the first known use
      of onboard sensors at this scale. Dipteran flies use halteres to provide
      gyroscopic velocity feedback, but it is unknown how other insects such as
      honeybees stabilize flight without these sensory organs. Our results, using a
      vehicle of similar size and dynamics to the honeybee, suggest how the ocelli
      could serve this role. 

PMID- 24942848
TI  - Magnetic orientation of garden warblers (Sylvia borin) under 1.4 MHz
      radiofrequency magnetic field.
AB  - We report on the experiments on orientation of a migratory songbird, the garden
      warbler (Sylvia borin), during the autumn migration period on the Courish Spit,
      Eastern Baltics. Birds in experimental cages, deprived of visual information,
      showed the seasonally appropriate direction of intended flight with respect to
      the magnetic meridian. Weak radiofrequency (RF) magnetic field (190 nT at 1.4
      MHz) disrupted this orientation ability. These results may be considered as an
      independent replication of earlier experiments, performed by the group of R. and
      W. Wiltschko with European robins (Erithacus rubecula). Confirmed outstanding
      sensitivity of the birds' magnetic compass to RF fields in the lower megahertz
      range demands for a revision of one of the mainstream theories of
      magnetoreception, the radical-pair model of birds' magnetic compass. 

PMID- 24942847
TI  - Fly wing vein patterns have spatial reproducibility of a single cell.
AB  - Developmental processes in multicellular organisms occur in fluctuating
      environments and are prone to noise, yet they produce complex patterns with
      astonishing reproducibility. We measure the left-right and inter-individual
      precision of bilaterally symmetric fly wings across the natural range of genetic
      and environmental conditions and find that wing vein patterns are specified with
      identical spatial precision and are reproducible to within a single-cell width.
      The early fly embryo operates at a similar degree of reproducibility, suggesting
      that the overall spatial precision of morphogenesis in Drosophila performs at the
      single-cell level. Could development be operating at the physical limit of what a
      biological system can achieve? 

PMID- 24942849
TI  - Ultrasound-guided continuous interscalene block: the influence of local
      anesthetic background delivery method on postoperative analgesia after shoulder
      surgery: a randomized trial.
AB  - BACKGROUND: Automated bolus delivery has recently been shown to reduce local
      anesthetic consumption and improve analgesia, compared with continuous infusion,
      in continuous sciatic and epidural block. However, there are few data on the
      influence of local anesthetic delivery method on local anesthetic consumption
      following interscalene blockade. This randomized, double-blind trial was designed
      to determine whether hourly automated perineural boluses (4 mL) of local
      anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses
      would result in a reduction in total local anesthesia consumption during
      continuous interscalene blockade after shoulder surgery compared with continuous
      perineural infusion (4 mL/h) plus patient-controlled PRN boluses. METHODS: One
      hundred one patients undergoing major shoulder surgery under general anesthesia
      with ultrasound-guided continuous interscalene block were randomly assigned to
      receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous
      infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery
      methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout
      time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local
      anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse
      events were recorded. RESULTS: There were no significant differences in either
      the number of PRN ropivacaine boluses or total 48 hour local anesthetic
      consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous
      infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group).
      Postoperative pain was similar in both groups; on day 2, the median average pain
      score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the
      automated bolus group (P = 0.54). Nor were any statistically significant
      intergroup differences observed with respect to morphine rescue, incidence of
      adverse events, or patient satisfaction. CONCLUSIONS: In continuous interscalene
      blockade under ultrasound guidance after shoulder surgery, automated boluses of
      local anesthetic combined with PRN boluses did not provide any reduction in local
      anesthetic consumption or rescue analgesia, compared with continuous infusion
      combined with PRN boluses.

PMID- 24942850
TI  - Perioperative research fellowship: planning, implementation, experience.
AB  - Perioperative outcomes research has gained widespread interest and is viewed as
      increasingly important among different specialties, including anesthesiology.
      Outcomes research studies serve to help in the adjustment of risk, allocation of
      resources, and formulation of hypotheses to guide future research. Pursuing high
      quality research projects requires familiarity with a wide range of research
      methods, and concepts are ideally learned in a dedicated setting. Skills
      associated with the use of these methods as well as with scientific publishing in
      general, however, are increasingly challenging to acquire. This article was
      intended to describe the curriculum and implementation of the Perioperative
      Medicine and Regional Anesthesia Research Fellowship at the Hospital for Special
      Surgery. We also proposed a method to evaluate the success of a research
      fellowship curriculum.

PMID- 24942852
TI  - A Hg(II)-mediated "signal-on" electrochemical glutathione sensor.
AB  - We report the design and fabrication of a DNA-based electrochemical sensor for
      detection of glutathione. Sensor signaling relies on glutathione's ability to
      chelate mercury Hg(II), displacing it from the thymine-Hg(II)-thymine complex
      formed between the surface-immobilized DNA probes. Our results show that this
      sensor is sensitive and selective enough to be employed in saliva.

PMID- 24942853
TI  - Study shows that more must be done to detect domestic violence.

PMID- 24942851
TI  - Pilot-scale comparison of four duckweed strains from different genera for
      potential application in nutrient recovery from wastewater and valuable biomass
      production.
AB  - The application potential of four duckweed strains from four genera, Wolffia
      globosa 0222, Lemna japonica 0223, Landoltia punctata 0224 and Spirodela
      polyrhiza 0225, were compared in four parallel pilot-scale wastewater treatment
      systems for more than 1 year. The results indicated that each duckweed strain had
      unique potential advantages. Unlike L. japonica 0223 and La. punctata 0224, which
      grow throughout the year, S. polyrhiza 0225 and W. globosa 0222 do not survive
      cold weather. For year round performance, L. japonica 0223 was best not only in
      dry biomass production (6.10 g.m(-2) .day(-1) ), but also in crude protein
      (35.50%), total amino acid (26.83%) and phosphorus (1.38%) content, plus recovery
      rates of total nitrogen (TN), total phosphorus (TP) and CO2 (0.31, 0.085 and 7.76
      g.m(-2) .day(-1) , respectively) and removal rates of TN and TP (0.66 and 0.089
      g.m(-2) .day(-1) , respectively). This strongly demonstrates that L. japonica
      0223 performed best in wastewater treatment and protein biomass production. Under
      nutrient starvation conditions, La. punctata 0224 had the highest starch content
      (45.84%), dry biomass production (4.81 g.m(-2) .day(-1) ) and starch accumulation
      (2.9 g.m(-2) .day(-1) ), making it best for starch biomass production. W. globosa
      0222 and S. polyrhiza 0225 showed increased flavonoid biomass production, with
      higher total flavonoid content (5.85% and 4.22%, respectively) and high dominant
      flavonoids (>60%). This study provides useful information for selecting the
      appropriate local duckweed strains for further application in wastewater
      treatment and valuable biomass production.

PMID- 24942854
TI  - State-of-the-art fluid management in critically ill patients.

PMID- 24942856
TI  - Imbalance between CD56+bright and CD56+dim natural killer cell subsets in the
      liver of patients with recurrent hepatitis C after liver transplantation.
AB  - Progressive liver fibrosis remains a major problem for patients with recurrent
      chronic hepatitis C(CHC) after liver transplantation (LT). However, the
      involvement of natural killer (NK) and natural killer T (NKT) cells, which
      predominate in the liver, in recurrent CHC after LT remains unclear.In the
      present study, we investigated the status of NK and NKT cells in the liver and
      peripheral blood obtained from 10 patients with recurrent CHC after LT (LT-C), 15
      patients with CHC, and 7 normal donors for living donor LT. CD56+ NK cells were
      separated into two subsets: CD56+bright subset, which is identified as major NK
      cytokine producer, and CD56+dim subset, which has greater spontaneous
      cytotoxicity. We found a significant decrease in the CD56+bright subset in the
      liver of patients with LT-C compared to patients with CHC (P<0.01) and normal
      donors (P=0.03). The expression of inhibitory NK cell receptor NKG2A was
      significantly increased on intrahepatic CD56+bright subset in LT-C patients, and
      activated CD69+CD56+dim NK cell subset was significantly increased in the liver
      of LT-C patients. Our results suggest that a significant imbalance between
      CD56+bright and CD56+dim NK cell subsets in the liver may contribute to the
      progression of recurrent CHC after LT.

PMID- 24942855
TI  - Fracture-based fabrication of normally closed, adjustable, and fully reversible
      microscale fluidic channels.
AB  - Adjustable fluidic structures play an important role in microfluidic systems.
      Fracture of multilayered materials under applied tension has been previously
      demonstrated as a convenient, simple, and inexpensive approach to fabricate
      nanoscale adjustable structures; here, it is demonstrated how to extend this
      concept to the microscale. This is achieved by a novel pairing of materials that
      leverages fracture mechanics to limit crack formation to a specified region,
      allowing to create size-controllable and adjustable microfluidic structures. This
      technique can be used to fabricate "normally closed" microfluidic channels that
      are completely reversible, a feature that is challenging to achieve in
      conventional systems without careful engineering controls. The adjustable
      microfluidic channels are then applied to mechanically lyse single cells, and
      subsequently manipulate the released nuclear chromatin, creating new
      possibilities for epigenetic analysis of single cells. This simple, versatile,
      and robust technology provides an easily accessible pathway to construct
      adjustable microfluidic structures, which will be useful in developing complex
      assays and experiments even in resource-limited settings. 

PMID- 24942857
TI  - Role of the third intracellular loop in the subtype-specific internalization and
      recycling of muscarinic M2 and M4 receptors.
AB  - Muscarinic M2, M4, and M2-M4 chimera receptors were transiently expressed in HEK
      293 tsA201 cells, and agonist-dependent internalization of these receptors and
      recycling of internalized receptors were examined by measuring the amount of cell
      surface receptors as [3H]N-methylscopolamine (NMS) binding activity. Coexpression
      of a dominant negative form of dynamin (DN-dynamin,dynamin K44A) greatly reduced
      the agonist-dependent internalization of M4 receptors but not of M2 receptors, as
      was reported by Vogler et al. (J Biol Chem 273, 12155-12160, 1998).The agonist
      dependent internalization of M2/M4-i3/M2 chimera receptors (M2 receptors with the
      i3 loop replaced by that of M4 receptors) was greatly reduced by co-expression of
      DN-dynamin as was the case for M4 receptors, whereas the agonist-dependent
      internalization of M4/M2-i3/M4 chimera receptors was hardly affected by co
      expression of DN-dynamin as was the case for M2 receptors.Internalized M2/M4
      i3/M2 receptors as well as internalized M4 receptors were shown to be recycled
      back to the cell surface after removal of agonists, whereas no recycling was
      observed for M4/M2-i3/M4 receptors as well as M2 receptors. These results
      indicate that the i3 loops of M2 and M4 receptors take a major role in their
      agonist-dependent internalization and recycling.

PMID- 24942859
TI  - Loss of periplakin expression is associated with pathological stage and cancer
      specific survival in patients with urothelial carcinoma of the urinary bladder.
AB  - The objective of this study was to determine periplakin expression in normal
      urothelium and bladder cancer tissues and the relationship to clinicopathological
      findings. Immunohistochemical staining for periplakin was carried out in 92
      archival radical cystectomy specimens, with immunoreactivity being stratified on
      a 0-6 scale. Immunohistochemical staining for periplakin was shown to be
      significantly lower in bladder cancer tissues compared to non-cancerous tissues
      including inflammation,hyperplasia and normal urothelium. Loss of periplakin
      expression was associated with pathological stage (P=0.04). In multivariate Cox
      regression analysis, loss of periplakin expression and positive lymph node status
      were independent prognostic factors for cancer-specific survival (P=0.03 and
      0.015; odds ratio=2.29 and 2.66; 95% confidence interval=1.085-4.814 and 1.214
      5.845, respectively). This new molecular marker may aid in identifying and
      selecting bladder cancer patients undergoing radical cystectomy who may
      potentially benefit from neoadjuvant or adjuvant therapy.

PMID- 24942858
TI  - Type II collagen peptide stimulates Akt leading to nuclear factor-kappaB
      activation: its inhibition by hyaluronan.
AB  - While nuclear factor (NF)-kappaB is a critical pathway for matrix
      metalloproteinase (MMP)-13 induction in chondrocytes, intracellular upstream
      events for NF-kappaB activation by the type II collagen peptide (CB12-II) with
      catabolic activities remain unclear. Hyaluronan (HA) of high molecular weight is
      clinically used for treatment of osteoarthritis (OA) by intra-articular
      injection. Although HA can suppress NF-kappaB activation by CB12-II, it is still
      obscure how HA affects intracellular upstream pathways leading to NF-kappaB up
      regulation in response to CB12-II. Thus, this study was aimed to investigate the
      involvement of phosphoinositide-3-OH kinase (PI3K)/Akt in the inhibition of CB12
      II-activated NF-kappaB pathway by HA in OA chondrocytes. In monolayer cultures,
      pre-treatment with HA of 2700 kDa significantly inhibited MMP-13 production by
      CB12-II-stimulated chondrocytes. CB12-II activated Akt and NF-kappaB whereas HA
      down-regulated CB12-II-stimulated phosphorylation of Akt and NF-kappaB.
      Inhibition studies using LY294002 revealed the requirement of PI3K/Akt pathway
      for CB12-II-stimulated NF-kappaB activation in association with MMP-13
      production.Pretreatment with anti-CD44 antibody reversed the inhibitory effects
      of HA on CB12-II-induced production of MMP-13 and activation of Akt and NF
      kappaB. Herein, we provided the first evidence that HA suppresses CB12-II
      activated PI3K/Akt pathway leading to down-regulation ofNF-kappaB with diminished
      MMP-13 production through interaction with CD44.

PMID- 24942860
TI  - A novel biomarker for acute kidney injury using TaqMan-based unmethylated DNA
      specific polymerase chain reaction.
AB  - There has been increasing interest in the use of circulating DNA as biomarkers
      for various tissue injuries, cancers, and fetal conditions. DNA methylation is a
      well-characterized mechanism underlying the epigenetic regulation of gene
      expression, and many diagnostic tests based on DNA methylation patterns have been
      developed. We developed a novel TaqMan-based assay for the detection of acute
      kidney injury using a hypomethylated promoter region of Slc22a12, a urate
      transporter specifically expressed in proximal tubular cells. Bisulfite
      sequencing analysis confirmed that the CpG islands in the promoter region of
      mouse Slc22a12 were preferentially hypomethylated in the kidney cortex. TaqMan
      minor groove binder (MGB) probes reliably discriminated the DNA fragments
      corresponding to the unmethylated and methylated promoter regions of Slc22a12.
      Plasma levels of unmethylated DNA corresponding to the Slc22a12 promoter region
      were undetectable at baseline and were significantly elevated after acute kidney
      cortex necrosis. This study showed the usefulness of the TaqMan system in
      discriminating methylated and unmethylated DNA fragments, and the similar
      strategy can be applied for establishing biomarkers for various cellular injuries
      or pathological conditions. 

PMID- 24942861
TI  - Effect of an angiotensin II receptor blocker and a calcium channel blocker on
      hypertension associated penile dysfunction in a rat model.
AB  - Possible effect of olmesartan, an angiotensin II receptor blocker (ARB), or
      nifedipine, an L-type calcium channel blocker, on penile dysfunction in the
      spontaneously hypertensive rat (SHR) was investigated in this study. Twelve-week
      old male SHRs were treated with olmesartan (1 or 3 mg/kg, per orally (p.o.)) or
      nifedipine (30 mg/kg, p.o.) once a day for 6 weeks. Wistar rats and SHRs with
      vehicle treatment were used as controls. Penile cGMP and malondialdehyde
      concentrations, and mRNA levels of endothelial and neuronal NO synthase (eNOS and
      nNOS) were measured. Penile function was evaluated by organ bath studies with
      norepinephrine-induced contractions and acetylcholine-induced relaxations. The
      SHR showed significantly increased blood pressure, decreased cGMP concentrations,
      increased malondialdehyde concentrations, decreased eNOS and nNOS mRNA levels,
      norepinephrine-induced hyper-contractions, and acetylcholine-induced hypo
      relaxations in the penile tissue compared to the Wistar rat. Both nifedipine and
      olmesartan significantly decreased blood pressure, increased cGMP and normalized
      the hyper-contractions and hypo-relaxations observed in the SHR group. However,
      not nifedipine but olmesartan improved the malondialdehyde concentrations and
      increased mRNA levels of eNOS and nNOS in the penis. Our results indicate that
      the hypertension-associated penile dysfunction might be treated with ARBs such as
      olmesartan better than calcium channel blockers, such as nifedipine.

PMID- 24942862
TI  - Diuresis by intravenous administration of xanthurenic acid in rats, and
      inhibition by probenecid.
AB  - The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan
      metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic
      acid works in the renal proximal tubule to produce the sulfate of xanthurenic
      acid as well as the liver, and we recently found that xanthurenic acid is a
      substrate of renal organic anion transporter OAT1. The purpose of this study was
      to examine relationship between the transport by OAT1 and diuresis related with
      xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes
      represented that probenecid inhibited xanthurenic acid uptake by rat OAT1
      (rOAT1). Although no diuresis was recognized by the intravenous injection of
      xanthurenic acid as a bolus in rats, the addition of its infusion exhibited
      natriuresis. Simultaneous administration of probenecid significantly decreased
      the urine volume and excreted amounts of sodium into urine. These findings showed
      the diuresis by the xanthurenic acid administration, and it was probenecid
      sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in
      part, contribute to its diuretic effect. 

PMID- 24942863
TI  - A predictive model of chronic kidney disease in patients with congenital
      anomalies of the kidney and urinary tract.
AB  - BACKGROUND: The antenatal detection of congenital anomalies of the kidney and
      urinary tract (CAKUT) has permitted early management of these conditions. The aim
      of this study was to identify predictive factors associated with chronic kidney
      disease (CKD) in CAKUT. We also propose a risk score of CKD. METHODS: In this
      cohort study, 822 patients with prenatally detected CAKUT were followed up for a
      median time of 43 months. The primary outcome was CKD stage III or higher. A
      predictive model was developed using the Cox proportional hazards model and
      evaluated by using c statistics. RESULTS: Chronic kidney disease occurred in 49
      of the 822 (6 %) children with prenatally detected CAKUT. The most accurate model
      included bilateral hydronephrosis, oligohydramnios, estimated glomerular
      filtration rate and postnatal diagnosis. The accuracy of the score was 0.95 [95 %
      confidence interval (CI) 0.89-0.99] and 0.92 (95 % CI 0.86-0.95) after a follow
      up of 2 and 10 years, respectively. Based on survival curves, we estimated that
      at 10 years of age, the probability of survival without CKD stage III was
      approximately 98 and 58 % for the patients assigned to the low-risk and high-risk
      groups, respectively (p < 0.001). CONCLUSIONS: Our predictive model of CKD may
      contribute to an early identification of a subgroup of patients at high risk for
      renal impairment. It should be pointed out, however, that this model requires
      external validation in a different cohort.

PMID- 24942864
TI  - Elucidation of the preferred routes of C8-vinyl reduction in chlorophyll and
      bacteriochlorophyll biosynthesis.
AB  - Most of the chlorophylls and bacteriochlorophylls utilized for light harvesting
      by phototrophic organisms carry an ethyl group at the C8 position of the
      molecule, the product of a C8-vinyl reductase acting on a
      chlorophyll/bacteriochlorophyll biosynthetic precursor. Two unrelated classes of
      C8-vinyl reductase are known to exist, BciA and BciB, found in the purple
      phototroph Rhodobacter sphaeroides and the cyanobacterium Synechocystis sp.
      PCC6803 respectively. We constructed strains of each bacterium with the native C8
      vinyl reductase swapped for the other class of the enzyme, and combined these
      replacements with a series of deletions of the native bch and chl genes. In vivo
      data indicate that the preferred substrates for both classes of the enzyme is C8
      vinyl chlorophyllide, with C8-vinyl protochlorophyllide reduced only under
      conditions in which this pigment accumulates as a result of perturbed formation
      of chlorophyllide. 

PMID- 24942865
TI  - Transcriptional and posttranslational regulation of insulin-like growth factor
      binding protein-3 by Akt3.
AB  - Insulin-like growth factor (IGF)-dependent and -independent antitumor activities
      of insulin-like growth factor binding protein-3 (IGFBP-3) have been proposed in
      human non-small cell lung cancer (NSCLC) cells. However, the mechanism underlying
      regulation of IGFBP-3 expression in NSCLC cells is not well understood. In this
      study, we show that activation of Akt, especially Akt3, plays a major role in the
      mRNA expression and protein stability of IGFBP-3 and thus antitumor activities of
      IGFBP-3 in NSCLC cells. When Akt was activated by genomic or pharmacologic
      approaches, IGFBP-3 transcription and protein stability were decreased.
      Conversely, suppression of Akt increased IGFBP-3 mRNA levels and protein
      stability in NSCLC cell lines. Characterization of the effects of constitutively
      active form of each Akt subtype (HA-Akt-DD) on IGFBP-3 expression in NSCLC cells
      and a xenograft model indicated that Akt3 plays a major role in the Akt-mediated
      regulation of IGFBP-3 expression and thus suppression of Akt effectively enhances
      the antitumor activities of IGFBP-3 in NSCLC cells with Akt3 overactivation.
      Collectively, these data suggest a novel function of Akt3 as a negative regulator
      of IGFBP-3, indicating the possible benefit of a combined inhibition of IGFBP-3
      and Akt3 for the treatment of patients with NSCLC. 

PMID- 24942867
TI  - RECQ helicase RECQL4 participates in non-homologous end joining and interacts
      with the Ku complex.
AB  - RECQL4, a member of the RecQ helicase family, is a multifunctional participant in
      DNA metabolism. RECQL4 protein participates in several functions both in the
      nucleus and in the cytoplasm of the cell, and mutations in human RECQL4 are
      associated with three genetic disorders: Rothmund-Thomson, RAPADILINO and Baller
      Gerold syndromes. We previously reported that RECQL4 is recruited to laser
      induced DNA double-strand breaks (DSB). Here, we have characterized the
      functional roles of RECQL4 in the non-homologous end joining (NHEJ) pathway of
      DSB repair. In an in vitro NHEJ assay that depends on the activity of DNA
      dependent protein kinase (DNA-PK), extracts from RECQL4 knockdown cells display
      reduced end-joining activity on DNA substrates with cohesive and non-cohesive
      ends. Depletion of RECQL4 also reduced the end joining activity on a GFP reporter
      plasmid in vivo. Knockdown of RECQL4 increased the sensitivity of cells to gamma
      irradiation and resulted in accumulation of 53BP1 foci after irradiation,
      indicating defects in the processing of DSB. We find that RECQL4 interacts with
      the Ku70/Ku80 heterodimer, part of the DNA-PK complex, via its N-terminal domain.
      Further, RECQL4 stimulates higher order DNA binding of Ku70/Ku80 to a blunt end
      DNA substrate. Taken together, these results implicate that RECQL4 participates
      in the NHEJ pathway of DSB repair via a functional interaction with the Ku70/Ku80
      complex. This is the first study to provide both in vitro and in vivo evidence
      for a role of a RecQ helicase in NHEJ. 

PMID- 24942868
TI  - Nonnutritive sweeteners are not supernormal stimuli.
AB  - BACKGROUND: It is often claimed that nonnutritive sweeteners (NNS) are 'sweeter
      than sugar', with the implicit implication that high-potency sweeteners are
      supernormal stimuli that encourage exaggerated responses. This study aimed to
      investigate the perceived sweetness intensity of a variety of nutritive
      sweeteners (sucrose, maple syrup and agave nectar) and NNS (acesulfame-K (AceK),
      rebaudioside A (RebA), aspartame and sucralose) in a large cohort of untrained
      participants using contemporary psychophysical methods. METHODS: Participants
      (n=401 total) rated the intensity of sweet, bitter and metallic sensations for
      nutritive sweeteners and NNS in water using the general labeled magnitude scale.
      RESULTS: Sigmoidal dose-response functions were observed for all stimuli except
      AceK. That is, sucrose follows a sigmoidal function if the data are not
      artifactually linearized via prior training. More critically, there is no
      evidence that NNS have a maximal sweetness (intensity) greater than sucrose;
      indeed, the maximal sweetness for AceK, RebA and sucralose were significantly
      lower than that for concentrated sucrose. For these sweeteners, mixture
      suppression due to endogenous dose-dependent bitter or metallic sensations
      appears to limit maximal perceived sweetness. CONCLUSIONS: In terms of perceived
      sweetness, NNS cannot be considered supernormal stimuli. These data do not
      support the view that NNS hijack or overstimulate sweet receptors to produce
      elevated sweet sensations.

PMID- 24942866
TI  - Caught in the cross fire: p53 in inflammation.
AB  - The p53 transcription factor is a major tumor suppressor, whose diverse
      activities serve to ensure genome stability and inhibit neoplastic processes. In
      recent years, it is becoming increasingly clear that p53 also plays a broader
      role in maintaining cellular homeostasis, as well as contributing to tissue
      homeostasis in a non-cell-autonomous fashion. Chronic inflammation is a potential
      cancer-promoting condition, and as such is also within the radar of p53, which
      mounts a multifaceted attempt to prevent the escalation of chronic tissue
      imbalance into neoplasia. Recent understanding of the p53 pathway and other
      family members reveals a broad interaction with inflammatory elements such as
      reactive oxygen and nitrogen species, cytokines, infectious agents and major
      immune-regulatory pathways like nuclear factor-kappaB. This complex cross talk is
      highly dependent on p53 status, as different p53 isoforms and p53 mutants can
      mediate different responses and even promote chronic inflammation and associated
      cancer, acting in the tumor cells as well as in the stromal and immune
      compartments. 

PMID- 24942869
TI  - Prenatal vitamin intake during pregnancy and offspring obesity.
AB  - BACKGROUND/OBJECTIVES: In animal studies, exposure to multivitamins may be
      associated with obesity in the offspring; however, data in humans are sparse. We
      therefore examined the association between prenatal vitamin intake during
      pregnancy and offspring obesity. SUBJECTS/METHODS: We investigated the
      association between prenatal vitamin intake and obesity among 29,160 mother
      daughter dyads in the Nurses' Health Study II. Mothers of participants provided
      information on prenatal vitamin use during pregnancy with the nurse daughter.
      Information on body fatness at ages 5 and 10, body mass index (BMI) at age 18,
      weight in 1989 and 2009, waist circumference, and height was obtained from the
      daughter. Polytomous logistic regression was used to predict BMI in early
      adulthood and adulthood, and body fatness in childhood. Linear regression was
      used to predict waist circumference in adulthood. RESULTS: In utero exposure to
      prenatal vitamins was not associated with body fatness, either in childhood or in
      adulthood. Women whose mothers took prenatal vitamins during pregnancy had a
      covariate-adjusted odds ratio (OR) of being obese in adulthood of 0.99 (95%
      confidence interval (CI) 0.92-1.05, P-value = 0.68) compared with women whose
      mothers did not take prenatal vitamins. Women whose mothers took prenatal
      vitamins during pregnancy had a covariate-adjusted OR of having the largest body
      shape at age 5 of 1.02 (95% CI 0.90-1.15, P-value = 0.78). In additional
      analyses, in utero exposure to prenatal vitamins was also unrelated to adult
      abdominal adiposity. CONCLUSIONS: Exposure to prenatal vitamins was not
      associated with body fatness either in childhood or in adulthood.

PMID- 24942871
TI  - Appendiceal mucinous neoplasm: an uncommon cause of right lower quadrant pain.

PMID- 24942870
TI  - Effects of body size and change in body size from infancy through childhood on
      body mass index in adulthood.
AB  - BACKGROUND: Weight and weight gain throughout infancy are related to later
      obesity, but whether the strength of the associations varies during the infancy
      period is uncertain. AIMS: Our aims were to identify the period of infancy when
      change in body weight has the strongest association with adult body mass index
      (BMI) and also the extent to which these associations during infancy are mediated
      through childhood BMI. METHODS: The Copenhagen Perinatal Cohort, in which
      participants were followed from birth through 42 years of age, provided
      information on weight at 12 months and BMI at 42 years for 1633 individuals.
      Information on weight at birth, 2 weeks, 1, 2, 3, 4 and 6 months was retrieved
      from health visitors' records and information on BMI at ages 7 and 13 years from
      school health records. The associations of infant weight and weight gain standard
      deviation scores (SDS) with adult BMI-SDS were analyzed using multiple linear
      regression and path analysis. RESULTS: Higher-weight-SDS at all ages from birth
      to an age 12 months were associated with higher-BMI-SDS at 42 years (regression
      coefficients 0.08-0.12). Infant weight gain-SDS was associated with greater BMI
      SDS at 42 years only between birth and 3 months (0.09, 95% confidence intervals
      (CI) 0.04, 0.15) driven by an association between 2 and 3 months (0.12, 95% CI:
      0.04, 0.20). The latter was partly mediated through later BMI in the path
      analysis. Infant weight gain-SDS between 3 and 12 months was not associated with
      greater BMI-SDS at 42 years. CONCLUSIONS: Faster weight gain during only the
      first 3 months of infancy was associated with increased adult BMI, although not
      in a consistent monthly pattern. Adult BMI is more sensitive to high weight gain
      during early infancy than late infancy, but not specifically to the first month
      of life.

PMID- 24942873
TI  - Diverging opinions about shared decisions.

PMID- 24942872
TI  - Prenatal infection affects the neuronal architecture and cognitive function in
      adult mice.
AB  - Environmental factors such as prenatal infection are involved in the pathogenic
      processes of neurodevelopmental psychiatric disorders. In the present study, we
      administered a viral mimic, polyriboinosinic-polyribocytidylic acid (poly I:C, 20
      mg/kg, i.p.), to pregnant B6 mice at gestational day 9.5. Neonates born to these
      poly I:C-treated dams showed an increase of microglia in the hippocampus,
      indicating an activation of the immune system in the brains. Moreover, a
      significant increase in the number of dopamine-producing neurons in the ventral
      tegmental area was observed in adult male poly I:C offspring compared with age
      matched saline offspring. Poly I:C offspring also exhibited hypolocomotor
      activity in a novel open-field arena but did not display signs of anxiety or
      depression in the elevated plus maze or the forced swim test, respectively.
      However, the short-term memory of the poly I:C offspring was impaired in a novel
      object recognition task. Therefore, the dendritic architecture of granule cells
      in the dentate gyrus (DG) and pyramidal neurons in the medial prefrontal cortex
      (mPFC) were examined. The dendritic complexity was reduced in the DG granule
      cells of the poly I:C offspring and exhibited shorter dendritic length compared
      with the saline offspring. The density of dendritic spines in the DG granule
      cells was also decreased in the poly I:C offspring. Furthermore, the dendritic
      complexity and spine density were reduced in layer II/III mPFC pyramidal neurons
      of the poly I:C offspring. Together, these data demonstrate impaired short-term
      memory and altered dendritic architecture in adult poly I:C offspring, which
      validates the prenatal infection paradigm as a model for neurodevelopmental
      psychiatric disorders.

PMID- 24942874
TI  - Cycloastragenol, a triterpene aglycone derived from Radix astragali, suppresses
      the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.
AB  - Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the
      Chinese herbal medicine Radix astragali, was reported to promote the
      phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we
      investigated the effect of CAG on adipogenesis. The image-based Nile red staining
      analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in
      3T3-L1 adipocytes with the IC50 value of 13.0 MUM. Meanwhile, cytotoxicity assay
      provided evidence that CAG was free of injury on HepG2 cells up to 60 MUM. In
      addition, using calcium mobilization assay, we observed that CAG stimulated
      calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50
      value was determined as 21.9 MUM. There were proofs that elevated intracellular
      calcium played a vital role in suppressing adipocyte differentiation. The current
      findings demonstrated that CAG was a potential therapeutic candidate for
      alleviating obesity and hyperlipidemia.

PMID- 24942875
TI  - Tissue inhibitor of metalloproteinase gene from pearl oyster Pinctada martensii
      participates in nacre formation.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are nature inhibitors of matrix
      metalloproteinases and play a vital role in the regulation of extracellular
      matrix turnover, tissue remodeling and bone formation. In this study, the
      molecular characterization of TIMP and its potential function in nacre formation
      was described in pearl oyster Pinctada martensii. The cDNA of TIMP gene in P.
      martensii (Pm-TIMP) was 901 bp long, containing a 5' untranslated region (UTR) of
      51 bp, a 3' UTR of 169 bp, and an open reading fragment (ORF) of 681 bp encoding
      226 amino acids with an estimated molecular mass of 23.37 kDa and a theoretical
      isoelectric point of 5.42; The predicted amino acid sequence had a signal
      peptide, 13 cysteine residues, a N-terminal domain and a C-terminal domain,
      similar to that from other species. Amino acid multiple alignment showed Pm-TIMP
      had the highest (41%) identity to that from Crassostrea gigas. Tissue expression
      analysis indicated Pm-TIMP was highly expressed in nacre formation related
      tissues, including mantle and pearl sac. After decreasing Pm-TIMP gene expression
      by RNA interference (RNAi) technology in the mantle pallium, the inner nacreous
      layer of the shells showed a disordered growth. These results indicated that the
      obtained Pm-TIMP in this study participated in nacre formation.

PMID- 24942876
TI  - Simplified method for cell-specific gene expression analysis in Caenorhabditis
      elegans.
AB  - In the neural circuit functional identities of individual neurons are mainly
      specified by their differential gene expression patterns. Unveiling functional
      roles of each neuron requires cell-specific interrogation of neural circuitry in
      the context of gene expressions. The mRNA tagging strategy in Caenorhabditis
      elegans is a powerful technique, in which cell-specific transcripts can be
      isolated by co-immunoprecipitating the complexes of mRNAs and epitope-tagged
      poly(A) binding protein (3* FLAG-PAB-1), expressed in target neurons. However,
      the conventional protocol requires laborious and time-consuming procedures;
      chromosomal integration of gene encoding 3* FLAG-PAB-1 and bleaching of obtained
      integrant animals for the isolation of huge amounts of synchronized animals. In
      this paper, we have presented a simplified methodology for cell-specific mRNA
      tagging analysis in C. elegans. We show that mRNA tagging was achieved using
      transgenic animals expressing 3* FLAG-PAB-1 as an extrachromosomal array under
      the control of the flp-18 promoter, without the chromosomal integration
      procedure. Furthermore, we successfully isolated cell-specific mRNAs from adult
      transgenic animals synchronously grown from eggs laid by gravid adults during a
      time window of 3h. This simplification facilitates the implementation of cell
      specific gene expression analysis of C. elegans, which contributes to the
      understanding of neural circuitry at a cell-specific resolution. 

PMID- 24942877
TI  - The grapevine tonoplast aquaporin TIP2;1 is a pressure gated water channel.
AB  - In plants, the vacuole is a multifunctional organelle with an important role in
      the maintenance of the intracellular space. Tonoplast membranes are highly
      permeable to water due to their content in aquaporins TIPs (Tonoplast Intrinsic
      Proteins) that allow the rapid water influx creating an internal turgor pressure
      responsible for cell expansion, elongation and shape. The aim of the present
      study was to evaluate if the grapevine Vitis vinifera TIP2;1 would operate as a
      possible volume regulator gated by membrane surface tension. For that, the wild
      type VvTIP2;1 and a non-functional mutated form were heterologous expressed in
      yeast. Using an experimental strategy in which cells are incubated in external
      media that induce an increase in internal hydrostatic pressure and consequently
      membrane surface tension, we were able to compare the osmotic permeability (Pf)
      and the activation energy for water transport (Ea) of yeast strains expressing
      the functional and a non-functional TIP2;1. We found Pf and Ea dependence on
      internal turgor pressure only for the strain harboring the functional aquaporin
      indicating that TIP2;1 activity is regulated by membrane tension changing from an
      open to a closed state in an internal pressure dependent manner. This turgor
      dependent gating of TIP2;1 might be a mechanism to regulate vacuolar size and
      shape in plants withstanding hostile drought conditions such as grapevine. 

PMID- 24942878
TI  - High glucose modifies transient receptor potential canonical type 6 channels via
      increased oxidative stress and syndecan-4 in human podocytes.
AB  - Transient receptor potential canonical (TRPC) channels type 6 play an important
      role in the function of human podocytes. Diabetic nephropathy is characterized by
      altered TRPC6 expression and functions of podocytes. Thus, we hypothesized that
      high glucose modifies TRPC6 channels via increased oxidative stress and syndecan
      4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions
      (5.6 mmol/L D-glucose), high glucose (30 mmol/L D-glucose or L-glucose), 100
      MUmol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic
      tempol (100 MUmol/L). TRPC6 and SDC-4 transcripts and protein expression were
      measured using RT-PCR and in-cell Western assay. Intracellular reactive oxygen
      species (ROS) and cytosolic calcium were measured using fluorescent dye
      techniques. High D-glucose increased TRPC6 transcripts to 8.66+/-4.08 (p<0.05)
      and TRPC6 protein expression to 1.44+/-0.07 (p<0.05) without altering SDC-4
      transcripts or protein expression. The D-glucose induced increase of TRPC6
      expression was blocked by tempol. Increased oxidative stress using peroxynitrite
      significantly increased TRPC6 transcripts to 4.29+/-1.26 (p<0.05) and TRPC6
      protein expression to 1.28+/-0.05 (p<0.05) without altering SDC-4 transcripts or
      protein expression. In human podocytes transfected with scrambled siRNA, high D
      glucose increased ROS after 90 min to 3.55+/-0.08 arbitrary units while 5.6
      mmol/L D-glucose increased ROS to 2.49+/-0.09 (p<0.001) only. The increase in ROS
      was inhibited by tempol and by SDC-4 knockdown. High glucose modifies TRPC6
      channels and ROS production via SDC-4 in human podocytes.

PMID- 24942879
TI  - Functional analysis of the Hikeshi-like protein and its interaction with HSP70 in
      Arabidopsis.
AB  - Heat shock proteins (HSPs) refold damaged proteins and are an essential component
      of the heat shock response. Previously, the 70 kDa heat shock protein (HSP70) has
      been reported to translocate into the nucleus in a heat-dependent manner in many
      organisms. In humans, the heat-induced translocation of HSP70 requires the
      nuclear carrier protein Hikeshi. In the Arabidopsis genome, only one gene encodes
      a protein with high homology to Hikeshi, and we named this homolog Hikeshi-like
      (HKL) protein. In this study, we show that two Arabidopsis HSP70 isoforms
      accumulate in the nucleus in response to heat shock and that HKL interacts with
      these HSP70s. Our histochemical analysis revealed that HKL is predominantly
      expressed in meristematic tissues, suggesting the potential importance of HKL
      during cell division in Arabidopsis. In addition, we show that HKL regulates
      HSP70 localization, and HKL overexpression conferred thermotolerance to
      transgenic Arabidopsis plants. Our results suggest that HKL plays a positive role
      in the thermotolerance of Arabidopsis plants and cooperatively interacts with
      HSP70.

PMID- 24942880
TI  - In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing
      ion channel 3.
AB  - Acid sensing ion channels (ASICs) are proton-gated cation channels that are
      expressed throughout the nervous system and have been implicated in mediating
      sensory perception of noxious stimuli. Amongst the six ASIC isoforms, ASIC1a, 1b,
      2a and 3 form proton-gated homomers, which differ in their activation and
      inactivation kinetics, expression profiles and pharmacological modulation;
      protons do not gate ASIC2b and ASIC4. As with many other ion channels, structure
      function studies of ASICs have been greatly aided by the discovery of some toxins
      that act in isoform-specific ways. ASIC3 is predominantly expressed by sensory
      neurons of the peripheral nervous system where it acts to detect acid as a
      noxious stimulus and thus plays an important role in nociception. ASIC3 is the
      only ASIC subunit that is inhibited by the sea anemone (Anthopleura
      elegantissima)-derived toxin APETx2. However, the molecular mechanism by which
      APETx2 interacts with ASIC3 remains largely unknown. In this study, we made a
      homology model of ASIC3 and used extensive protein-protein docking to predict for
      the first time, the probable sites of APETx2 interaction on ASIC3. Additionally,
      using computational alanine scanning, we also suggest the 'hot-spots' that are
      likely to be critical for ASIC3-APETx2 interaction. 

PMID- 24942881
TI  - Negative feedback regulation of NF-kappaB-inducing kinase is proteasome-dependent
      but does not require cellular inhibitors of apoptosis.
AB  - Non-canonical NF-kappaB signaling is controlled by the precise regulation of NF
      kappaB inducing kinase (NIK) stability. NIK is constitutively ubiquitylated by
      cellular inhibitor of apoptosis (cIAP) proteins 1 and 2, leading to its complete
      proteasomal degradation in resting cells. Following stimulation, cIAP-mediated
      ubiquitylation of NIK ceases and NIK is stabilized, allowing for inhibitor of
      kappaB kinase (IKK)alpha activation and non-canonical NF-kappaB signaling. Non
      canonical NF-kappaB signaling is terminated by feedback phosphorylation of NIK by
      IKKalpha that promotes NIK degradation; however, the mechanism of active NIK
      protein turnover remains unknown. To address this question, we established a
      strategy to precisely distinguish between basal degradation of newly synthesized
      endogenous NIK and induced active NIK in stimulated cells. Using this approach,
      we found that IKKalpha-mediated degradation of signal-induced activated NIK
      occurs through the proteasome. To determine whether cIAP1 or cIAP2 play a role in
      active NIK turnover, we utilized a Smac mimetic (GT13072), which promotes
      degradation of these E3 ubiquitin ligases. As expected, GT13072 stabilized NIK in
      resting cells. However, loss of the cIAPs did not inhibit proteasome-dependent
      turnover of signal-induced NIK showing that unlike the basal regulatory
      mechanism, active NIK turnover is independent of cIAP1 and cIAP2. Our results
      therefore establish that the negative feedback control of IKKalpha-mediated NIK
      turnover occurs via a novel proteasome-dependent and cIAP-independent mechanism. 

PMID- 24942882
TI  - A de novo monoclonal immunoglobulin deposition disease in a kidney transplant
      recipient: a case report.
AB  - INTRODUCTION: Myeloma following kidney transplantation is a rare entity. It can
      be divided into two groups: relapse of a previous myeloma and de novo myeloma.
      Some of these myelomas can be complicated by a monoclonal immunoglobulin
      deposition disease, which is even less common. Less than ten cases of monoclonal
      immunoglobulin deposition disease after renal graft have been reported in the
      literature. The treatment of these patients is not well codified. CASE
      PRESENTATION: We report the case of a 43-year-old white European man who received
      a renal transplant for a nephropathy of unknown etiology and developed a
      nephrotic syndrome with kidney failure at 2-years follow-up. We diagnosed a de
      novo monoclonal immunoglobulin deposition disease associated with a kappa light
      chain multiple myeloma, which is a very uncommon presentation for this disease.
      Three risk factors were identified in this patient: Epstein-Barr virus
      reactivation with cytomegalovirus co-infection; intensified immunosuppressive
      therapy during two previous rejection episodes; and human leukocyte antigen-B
      mismatches. Chemotherapy treatment and decrease in the immunosuppressive therapy
      were followed by remission and slight improvement of renal function. A relapse
      occurred 8 months later and his renal function worsened rapidly requiring
      hemodialysis. He died from septic shock 4 years after the diagnosis of monoclonal
      immunoglobulin deposition disease. CONCLUSIONS: This rare case of post-transplant
      lymphoproliferative disorder with an uncommon presentation illustrates the fact
      that treatment in such a situation is very difficult to manage because of a small
      number of patients reported and a lack of information on this disease. There are
      no guidelines, especially concerning the immunosuppressive therapy management.

PMID- 24942884
TI  - A case of recurrent respiratory papillomatosis with malignant transformation,
      HPV11 DNAemia, high L1 antibody titre and a fatal papillary endocardial lesion.
AB  - BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare disease, which
      is characterised by the growth of papillomavirus-induced papillomas within the
      respiratory tract. Malignant transformation occurs in less than 1% of the cases.
      CASE PRESENTATION: We report a case of human papillomavirus (HPV) type 11
      associated juvenile-onset RRP (JORRP) initially diagnosed at the age of two
      years. Remarkably high copy numbers of HPV11 DNA and antibody titres targeting
      the capsid protein L1 were detected in the patient's serum. The patient developed
      squamous cell carcinomas in both lungs and extraordinarily an HPV11 DNA-positive
      papillary endocardial lesion in the left atrium of the heart, which caused
      thromboembolic events leading to the patient's death at 19 years old. CONCLUSION:
      We here report a severe case of JORRP hallmarked by HPV11 DNAemia and very high
      antibody titres directed against the major viral capsid protein L1. Furthermore,
      the extent of malignant transformation and the discovery of a very rare fatal
      endocardial lesion highlight the unpredictability of JORRP and the complexity of
      its clinical management.

PMID- 24942885
TI  - A unique gene cluster for the utilization of the mucosal and human milk
      associated glycans galacto-N-biose and lacto-N-biose in Lactobacillus casei.
AB  - The probiotic Lactobacillus casei catabolizes galacto-N-biose (GNB) and lacto-N
      biose (LNB) by using a transport system and metabolic routes different from those
      of Bifidobacterium. L. casei contains a gene cluster, gnbREFGBCDA, involved in
      the metabolism of GNB, LNB and also N-acetylgalactosamine. Inactivation of gnbC
      (EIIC) or ptsI (Enzyme I) of the phosphoenolpyruvate : sugar phosphotransferase
      system (PTS) prevented the growth on those three carbohydrates, indicating that
      they are transported and phosphorylated by the same PTS(Gnb) . Enzyme activities
      and growth analysis with knockout mutants showed that GnbG (phospho-beta
      galactosidase) hydrolyses both disaccharides. However, GnbF (N
      acetylgalactosamine-6P deacetylase) and GnbE (galactosamine-6P
      isomerase/deaminase) are involved in GNB but not in LNB fermentation. The
      utilization of LNB depends on nagA (N-acetylglucosamine-6P deacetylase), showing
      that the N-acetylhexosamine moieties of GNB and LNB follow different catabolic
      routes. A lacAB mutant (galactose-6P isomerase) was impaired in GNB and LNB
      utilization, indicating that their galactose moiety is channelled through the
      tagatose-6P pathway. Transcriptional analysis showed that the gnb operon is
      regulated by substrate-specific induction mediated by the transcriptional
      repressor GnbR, which binds to a 26 bp DNA region containing inverted repeats
      exhibiting a 2T/2A conserved core. The data represent the first characterization
      of novel metabolic pathways for human milk oligosaccharides and glycoconjugate
      structures in Firmicutes. 

PMID- 24942883
TI  - Wnt-Notch signalling crosstalk in development and disease.
AB  - The Notch and Wnt pathways are two of only a handful of highly conserved
      signalling pathways that control cell-fate decisions during animal development
      (Pires-daSilva and Sommer in Nat Rev Genet 4: 39-49, 2003). These two pathways
      are required together to regulate many aspects of metazoan development, ranging
      from germ layer patterning in sea urchins (Peter and Davidson in Nature 474: 635
      639, 2011) to the formation and patterning of the fly wing (Axelrod et al in
      Science 271:1826-1832, 1996; Micchelli et al in Development 124:1485-1495, 1997;
      Rulifson et al in Nature 384:72-74, 1996), the spacing of the ciliated cells in
      the epidermis of frog embryos (Collu et al in Development 139:4405-4415, 2012)
      and the maintenance and turnover of the skin, gut lining and mammary gland in
      mammals (Clayton et al in Nature 446:185-189, 2007; Clevers in Cell 154:274-284,
      2013; Doupe et al in Dev Cell 18:317-323, 2010; Lim et al in Science 342:1226
      1230, 2013; Lowell et al in Curr Biol 10:491-500, 2000; van et al in Nature
      435:959-963, 2005; Yin et al in Nat Methods 11:106-112, 2013). In addition, many
      diseases, including several cancers, are caused by aberrant signalling through
      the two pathways (Bolos et al in Endocr Rev 28: 339-363, 2007; Clevers in Cell
      127: 469-480, 2006). In this review, we will outline the two signalling pathways,
      describe the different points of interaction between them, and cover how these
      interactions influence development and disease. 

PMID- 24942886
TI  - Efficacy and safety of adalimumab as the first and second biologic agent in
      juvenile idiopathic arthritis: the German Biologics JIA Registry.
AB  - OBJECTIVE: To evaluate the efficacy and safety of adalimumab in patients with
      juvenile idiopathic arthritis (JIA). METHODS: Baseline demographic and clinical
      characteristics and disease activity parameters were prospectively documented in
      the German Biologics JIA Registry. Efficacy was determined using the American
      College of Rheumatology (ACR) Pediatric (Pedi) response criteria and the Juvenile
      Arthritis Disease Activity Score based on a 10-joint count (JADAS-10). Safety
      assessments were based on adverse event reports from the responsible physician.
      RESULTS: Two hundred eighty-nine patients with a total of 1,046 visits were
      identified (435.7 patient-years). A high proportion of patients demonstrated a
      significant response to treatment, with a marked decrease in the JADAS-10 score
      in both the biologics-naive group (which consisted of patients who had not
      received therapy with a biologic agent prior to initiation of adalimumab) and the
      biologic-switcher group (which consisted of patients who had been treated with a
      different biologic agent prior to initiation of adalimumab). The median JADAS-10
      score at treatment start was significantly higher in the biologics-naive group
      than in the biologic-switcher group (12.9 versus 8.5; P = 0.00044), although the
      score in the biologics-naive group was lower over the course of adalimumab
      treatment. ACR Pedi 30, 50, 70, and 90 scores were achieved in 63.4%, 61.0%,
      48.8%, and 34.2% of biologics-naive patients, respectively, at 6 months of
      treatment, while ACR Pedi 30, 50, 70, and 90 scores were achieved in 47.6%,
      38.1%, 21.9%, and 15.2% of biologic-switcher patients, respectively. Forty-eight
      patients experienced 222 adverse events (50.9 per 100 patient-years). Eleven were
      reported as serious (2.5 per 100 patient-years). No malignancies were observed
      during adalimumab exposure. There were 16 uveitis flares in 11 patients.
      Treatment was discontinued in 58 patients for the following reasons: inefficacy
      11.1%, adverse events 5.2%, remission 4.5%, patient request 11.8%, and other
      reasons 7.9%. CONCLUSION: Adalimumab appears to be highly effective in children
      and adolescents with JIA who have been previously treated with biologic agents
      and in children and adolescents who switched biologic agents. The treatment is
      safe and its efficacy is similar to that of other biologic agents used to treat
      JIA. Few patients discontinued therapy due to intolerance or inefficacy.

PMID- 24942887
TI  - Long-term recurrence of soft tissue sarcomas: prognostic factors and implications
      for prolonged follow-up.
AB  - BACKGROUND: To the authors' knowledge, the incidence of late recurrence (> 5
      years after initial management) is unknown and no prognostic factors for late
      events have been characterized in patients with soft tissue sarcomas. METHODS:
      Follow-up data from patients with localized soft tissue sarcoma who were included
      in the French Sarcoma Group database from January 1990 to June 2005 were
      reviewed. The outcomes of interest were the cumulative probabilities of late (> 5
      years) local and metastatic disease recurrence with death as a competing event.
      Estimations and 95% confidence intervals (95% CIs) were computed with the
      cumulative incidence function. RESULTS: A total of 719 patients who were alive
      and event free > 5 years after their initial diagnosis were included in the
      current study. Sixty-seven patients (9.3%) developed a late local recurrence and
      42 patients (5.8%) developed a late metastatic recurrence, respectively. On
      multivariate analysis, internal trunk location (hazard ratio [HR], 3.9; 95% CI,
      2.2-6.7 [P < .001]) and tumor size > 100 mm (HR, 2.1; 95% CI, 1.1-4 [P = .035])
      were the 2 factors found to be independently associated with an increased risk of
      late local recurrence. Grade > 1 (graded according to the French Federation of
      Cancer Centers Sarcoma Group) (HR, 4.7; 95% CI 1.1-21 [P = .04]) was the sole
      factor found to be independently associated with an increased risk of late
      metastatic recurrence. CONCLUSIONS: Late recurrence of soft tissue sarcoma is
      relatively uncommon. However, the results of the current study emphasize the
      critical role of long-term follow-up to detect late local disease recurrence in
      patients with retroperitoneal or very large soft tissue sarcomas, and late
      metastatic recurrence in patients with high-grade disease. Conversely, the
      prolonged follow-up of patients with grade 1 disease is not needed.

PMID- 24942888
TI  - Evaluating the health inequalities impact of area-based initiatives across the
      socioeconomic spectrum: a controlled intervention study of the New Deal for
      Communities, 2002-2008.
AB  - BACKGROUND: Previous evaluations of area-based initiatives have not compared
      intervention areas with the full range of areas from top to bottom of the social
      spectrum to evaluate their health inequalities impact. SETTING: Deprived areas
      subject to the New Deal for Communities (NDC) intervention, local deprivation
      matched comparator areas, and areas drawn from across the socioeconomic spectrum
      (representing high, medium and low deprivation) in England between 2002 and 2008.
      DATA: Secondary analysis of biannual repeat cross-sectional surveys collected for
      the NDC National Evaluation Team and the Health Survey for England (HSE).
      METHODS: Following data harmonisation, baseline and time trends in six health and
      social determinants of health outcomes were compared. Individual-level data were
      modelled using regression to adjust for age, sex, ethnic and socioeconomic
      differences among respondents. RESULTS: Compared with respondents in HSE low
      deprivation areas, those in NDC intervention areas experienced a significantly
      steeper improvement in education, a trend towards a steeper improvement in self
      rated health, and a significantly less steep reduction in smoking between 2002
      and 2008. In HSE high deprivation areas, significantly less steep improvements in
      five out of six outcomes were seen compared with HSE low deprivation areas.
      CONCLUSIONS: Although unable to consider prior trends and previous initiatives,
      our findings provide cautious optimism that well-resourced and constructed area
      based initiatives can reduce, or at least prevent the widening of, social
      inequalities for selected outcomes between the most and least deprived groups of
      areas.

PMID- 24942889
TI  - Impact of unemployment variations on suicide mortality in Western European
      countries (2000-2010).
AB  - BACKGROUND: A scientific debate is currently taking place on whether the 2008
      economic crisis caused an increase in suicide rates. Our main objective was to
      assess the impact of unemployment rate on suicide rate in Western European
      countries between 2000 and 2010. We then tried to estimate the excess number of
      suicides attributable to the increase of unemployment during the 2008-2010
      economic crisis. METHODS: The yearly suicide rates were modelled using a quasi
      Poisson model, controlling for sex, age, country and a linear time trend. For
      each country, the unemployment-suicide association was assessed, and the excess
      number of suicides attributable to the increase of unemployment was estimated.
      Sensitivity analyses were performed, notably in order to evaluate whether the
      unemployment-suicide association found was biased by a confounding context effect
      ('crisis effect'). RESULTS: A significant 0.3% overall increase in suicide rate
      for a 10% increase in unemployment rate (95% CI 0.1% to 0.5%) was highlighted.
      This association was significant in three countries: 0.7% (95% CI 0.0% to 1.4%)
      in the Netherlands, 1.0% (95% CI 0.2% to 1.8%) in the UK and 1.9% (95% CI 0.8% to
      2.9%) in France, with a significant excess number of suicides attributable to
      unemployment variations between 2008 and 2010 (respectively 57, 456 and 564). The
      association was modified inconsistently when adding a 'crisis effect' into the
      model. CONCLUSIONS: Unemployment and suicide rates are globally statistically
      associated in the investigated countries. However, this association is weak, and
      its amplitude and sensitivity to the 'crisis effect' vary across countries. This
      inconsistency provides arguments against its causal interpretation.

PMID- 24942890
TI  - Policy is political; our ideas about knowledge translation must be too.

PMID- 24942891
TI  - Shifting from hydrogen bond network to pi-pi stacking: a key mechanism for
      reversible thermochromic sulfonated poly(ether ether ketone).
AB  - Sulfonated poly(ether ether ketone) (SPEEK) thin film performs reversible
      thermochromic property by developing the color to be yellowish at the temperature
      above 190  degrees C. The detailed analyses based on temperature-dependent
      techniques suggest the thermal treatment inducing the shifting of the hydrogen
      bond network between the sulfonated group and the hydrated water molecules to the
      pi-pi stacking among aromatic rings in SPEEK chains. Although it is general that
      the polymer chain packing is unfavorable at high temperature, the present work
      shows a good example that when the polymer chains can form specific molecular
      interaction, such as pi-pi stacking, even in harsh thermal treatment, a
      rearrangement will effectively occur, which leads to an external stimuli
      responsive property. 

PMID- 24942892
TI  - Riverine and near coastal migration performance of hatchery brown trout Salmo
      trutta.
AB  - To study migration performance and return rates of hatchery brown trout Salmo
      trutta smolts the first 5 months after release, 50 fish in each year (fork
      length, LF , 158-288 mm) were in two subsequent years tagged with acoustic
      transmitters and recorded by automatic listening stations in the River Nidelva
      (central Norway), its estuary and in the marine environment. More than half of
      the smolts became anadromous migrants (52% in 2011 and 70% in 2012). The fish
      spent longer time in the estuary than in the marine environment and the results
      suggest that migratory behaviour of S. trutta smolts is not only restricted to be
      resident or anadrome-lacustrine, but that there is also an intermediary strategy
      of estuarine feeding. There were no differences in LF or mass between groups of
      smolts with different migration patterns. Return rates from the sea within the
      first 5 months after release were in both years 16%. Median progression rate in
      the river was 0.090 LF s(-1) but decreased significantly as the smolts entered
      the estuary (0.015 LF s(-1) ). The long residential time in the estuary may
      increase the risk of negative effects of anthropogenic activities in estuaries,
      such as harbours and industrial development, and special attention should be
      given to evaluate effects of such activities. 

PMID- 24942893
TI  - Corruption in healthcare in India: why the NHS should take an interest.

PMID- 24942894
TI  - Variations in molecular profile in NSCLC can be analyzed using cytological
      samples: development of EGFR resistance mutations and coexistence of ALK-EML4
      translocation in an EGFR-sensitive patient.
AB  - As a result of therapeutic advances, a revolution is taking place in the lung
      cancer field with major implications for pathologic diagnosis and tissue
      management. We report a case of a non-small cell lung carcinoma patient with
      coexistence of EGFR mutations and ALK-EML4 rearrangements that responded to EGFR
      inhibitors and in which the development of a new resistance mutation in exon 20
      of EGFR-determined treatment resistance. All the molecular determinations were
      performed in cytological samples. To our knowledge, this is the first case
      reported with these characteristics, and the 11th case described with coexistence
      of EGFR mutations and ALK-EML4 rearrangements. The EGFR L858R mutation in exon 21
      was found at diagnosis, and the patient presented a 4-year response to erlotinib.
      On progression, the T790M resistance mutation in the EGFR exon 20 was also
      confirmed in cytological samples. At this point, fluorescence in situ
      hybridization also detected ALK-EML4 translocation. This case emphasizes the
      usefulness of cytological samples for molecular analysis in lung adenocarcinoma,
      as well as the relevance of repeating biopsies/fine-needle aspirations in tumor
      recurrences to assess the mutation profile of the disease. 

PMID- 24942895
TI  - Oncocytic adenoma in a black thyroid.

PMID- 24942896
TI  - Clear cell adenocarcinoma arising in an adenomyoma of the broad ligament.
AB  - Extrauterine adenomyomas are extremely rare benign tumors of smooth muscles,
      endometrial glands, and endometrial stroma. Ectopic endometrial glands can
      undergo malignant change. The ovary is the most common site of malignant change
      in endometriosis. Cancer arising in extraovarian endometriosis is a rare event
      with limited cases in the literature. To the best of our knowledge, we present
      the first case of a clear cell adenocarcinoma arising from foci of ectopic
      endometrial tissue in an adenomyoma of the broad ligament. It supports the
      association between endometriomas and clear cell adenocarcinoma. Therefore,
      patients with a significant history of endometriosis may benefit from close
      follow-up or definitive surgery. 

PMID- 24942897
TI  - Enterocolic lymphocytic phlebitis as a newly recognized manifestation of IgG4
      related disease.
AB  - Herein we present a case of a 65-year-old woman with enterocolic lymphocytic
      phlebitis (ELP) who presented with anemic syndrome and in whom severe stenosis of
      the right flexure of large bowel was detected. The microscopic examination
      revealed fibrosis of the submucosa and lymphoplasmacytic phlebitis of small veins
      and venules, whereas arteries were spared. There were 110 IgG4-positive and 160
      IgG-positive plasma cells in 1 high-power field, respectively, with corresponding
      IgG4/IgG ratio of 0.69. The IgG4 serum level was 2.42 g/L. According to the
      currently proposed criteria, this ELP case is the first that may be diagnosed as
      definite IgG4-related disease (IgG4-RD). Although based on the sole case
      description, taken together with a recent review and a case report, we presume
      that a subset of ELPs is a manifestation of IgG4-RD. 

PMID- 24942898
TI  - Serological survey of tularemia among butchers and slaughterhouse workers in
      Iran.
AB  - BACKGROUND: Tularemia is a zoonotic disease caused by the Gram-negative bacterium
      Francisella tularensis. Human infections often occur through manipulation of
      infected animals or animal carcasses. METHODS: In this study, we determined the
      tularemia seroprevalence in butchers and slaughterhouse workers in 10 counties of
      Sistan and Baluchestan Province in Iran. RESULTS: A mean seroprevalence of 6.5%
      for IgG antibodies against F. tularensis was seen. The highest seropositivity
      rates were observed in the counties of Zabol and Nikhshahr. There was no
      difference in the seroprevalence rates between butchers and slaughterhouse
      workers (p=0.25). CONCLUSION: These data suggest that tularemia is endemic in
      Sistan and Baluchestan Province in Iran.

PMID- 24942899
TI  - Splenic infarction and malaria.
AB  - BACKGROUND: Splenic infarction is a well recognised complication of malaria that
      has been infrequently reported in the literature. METHODS: A review was performed
      to describe the spectrum of characteristics associated with this complication.
      RESULTS: Most patients presented with fever, left upper quadrant pain and/or
      splenomegaly, but no specific symptoms or signs appear to predict underlying
      infarction. The majority of cases reported were associated with autochthonous
      Plasmodium vivax infections, whereas cases reported in travellers were mostly due
      to P. falciparum acquired in Africa. CONCLUSION: Identification of infarction may
      allow specific recommendations for management, and associated complications such
      as splenic rupture should be excluded. Outcome is generally favourable and
      conservative management is the preferred option.

PMID- 24942900
TI  - Non-bacterial etiologies of diarrheal diseases in Afghanistan.
AB  - BACKGROUND: Microbial diarrheal diseases are one of the leading causes of child
      morbidity and mortality in developing countries. This study aimed to identify the
      main causes of non-bacterial diarrhea in Afghanistan. METHODS: A total of 699
      stools were collected from children aged under 5 years who presented with
      diarrhea at Indira Gandhi and Kandahar hospitals. Frozen aliquots were preserved
      for screening against rotavirus, astrovirus, adenovirus, norovirus,
      Cryptosporidium and Giardia, when bacterial cultures tested negative. Tests were
      performed at the hospitals after laboratory staff were trained and provided with
      enzyme-immunoassays and equipment. Results were confirmed at the U.S. Naval
      Medical Research Unit No. 3, Cairo, Egypt. RESULTS: Of the samples tested, 71.9%
      (503/699) were infected with one or more pathogens. However, the majority (85.8%;
      432/503) showed single infections: rotavirus (72.2%; 329/432), Cryptosporidium
      (14.1%; 61/432), Giardia (5.1%; 22/432), astrovirus (2.3%; 10/432), adenovirus
      (1.6%; 7/432) and norovirus (0.7%; 3/432). The remaining 14% (71/503) showed
      mixed infections of the tested pathogens. CONCLUSIONS: Non-bacterial pathogens
      were identified that could enable health officials to adopt more effective
      treatment and control measures for diarrhea in Afghanistan.

PMID- 24942901
TI  - Evaluation of the effects of comprehensive reform on primary healthcare
      institutions in Anhui Province.
AB  - BACKGROUND: In 2009, the Chinese Central Communist Party and the China State
      Council started to implement comprehensive healthcare reforms. The first round of
      reforms, involving Anhui province, was from 2009 to 2011, and focused on primary
      healthcare institutions. This study conducts an initial assessment of the effects
      of specific parts of the reforms in Anhui. METHODS: Mixed quantitative and
      qualitative methods were adopted for data collection. Seven hundred and three
      health institutions from 15 counties were randomly chosen. The practices,
      development, effects, problems, and other relevant information related to the
      reform were classified into four aspects: medicine management; personnel systems
      and income distribution mechanisms; compensation mechanisms for primary
      healthcare institutions; and strengthening the primary healthcare system. The
      effects of reform were analyzed by evaluating changes in compensation channels,
      visit costs, diagnosis and treatment structure, hardware, structures, efficiency,
      and behavior. RESULTS: A new system for authorizing drugs resulted in a total of
      857 new drugs being accessible at agreed prices through primary healthcare
      institutions in Anhui. The cost of the average outpatient visit decreased from
      35.29 RMB to 31.64 RMB, although for inpatients, the average cost increased from
      799.05 RMB to 992.60 RMB. The number of healthcare personnel decreased, but their
      workloads increased. The total revenue from government sources increased by
      41.09%, and the proportion of revenue from drugs decreased by 25.19%. The rate of
      diagnosis and treatment visits and outpatient visits to primary healthcare
      institutions increased. Finally, between 2008 and 2010, 1,195 standardized
      township hospitals, 14,134 village clinics, and 1,234 community health service
      institutions were constructed. CONCLUSION: The reform of primary healthcare
      institutions in Anhui has improved the personnel structures surrounding frontline
      healthcare workers, increased their incomes, improved work efficiency, and
      changed the compensation patterns of primary healthcare institutions, improved
      hardware, reduced drug prices, and, to some extent, improved the diagnosis and
      treatment structure. However, the reforms have not radically changed the behavior
      of medical workers or the visit patterns of patients. Approaches such as
      strengthening performance evaluation, and carrying out initiatives to further
      mobilize frontline healthcare workers, enhance rational drug use through improved
      training and educate patients, should be undertaken in the future.

PMID- 24942902
TI  - The Swedish Longitudinal Gambling Study (Swelogs): design and methods of the
      epidemiological (EP-) track.
AB  - Swelogs (Swedish Longitudinal Gambling Study) epidemiological (EP-) track is a
      prospective study with four waves of data-collection among Swedish citizens aged
      16-84 years at baseline. The major objectives of this track are to provide
      general population estimates of the prevalence and incidence of problem and at
      risk gambling and enable comparisons with the first Swedish national study on
      gambling and problem gambling (Swegs) conducted in 1997/1998. The overall study
      (Swelogs) comprises three tracks of data collection; one epidemiological, one in
      depth and one follow-up. It is expected to provide information that will inform
      the development of evidence-based methods and strategies to prevent the
      development of gambling problems. This paper gives an overview of the design of
      the epidemiological track, especially of its two first waves. The baseline wave,
      performed between October 2008 and August 2009, included 8165 subjects, of whom
      6021 were re-assessed one year later. A stratified random sampling procedure was
      applied. Computer-supported telephone interviews were used as the primary method.
      Postal questionnaires were used to follow-up those not reached by telephone. The
      response rate was 55% in the first wave and 74% in the second. The interview and
      questionnaire data are supplemented by register data.

PMID- 24942903
TI  - Detection of charges and molecules with self-assembled nano-oscillators.
AB  - Detection of a single or small amount of charges and molecules in biologically
      relevant aqueous solutions is a long-standing goal in analytical science and
      detection technology. Here we report on self-assembled nano-oscillators for
      charge and molecular binding detections in aqueous solutions. Each nano
      oscillator consists of a nanoparticle linked to a solid surface via a molecular
      tether. By applying an oscillating electric field normal to the surface, the
      nanoparticles oscillate, which is detected individually with ~0.1 nm accuracy by
      a plasmonic imaging technique. From the oscillation amplitude and phase, the
      charge of the nanoparticles is determined with a detection limit of ~0.18
      electron charges along with the charge polarity. We further demonstrate the
      detection of molecular binding with the self-assembled nano-oscillators. 

PMID- 24942904
TI  - Core lower urinary tract symptom score questionnaire: a psychometric analysis.
AB  - OBJECTIVES: To analyze the reliability and validity of the Japanese version of
      the core lower urinary symptom score questionnaire with psychometric methods.
      METHOD: The present study included 140 women and 125 men who filled in a core
      lower urinary symptom score questionnaire while attending two lectures on lower
      urinary tract symptoms. Missing response rates to individual questions were 1.5
      5.3%. After the descriptive analyses including box plot, Cronbach's alpha
      coefficients and Spearman's rho were calculated for reliability and validity
      assessment, respectively. Factor analysis was also carried out to explore the
      underlying structure. RESULTS: Of the scores for 10 core symptoms, the
      interquartile range for pain in the bladder and urethra was 0 in both sexes, and
      that for stress incontinence was 0 in men. Cronbach's alpha of the core lower
      urinary symptom score was 0.733 in women and 0.721 in men. Questions regarding
      daytime frequency, nocturia, urgency and urgency urinary incontinence, and those
      on slow stream, straining and feeling of incomplete emptying were significantly
      correlated with each other in both sexes. Pain in the urethra and bladder showed
      more extensive associations in women than in men. Factor analysis showed four
      components in both sexes: the first was storage symptoms, second was voiding
      symptoms, third was pain and the fourth was urinary incontinence. CONCLUSIONS:
      The core lower urinary symptom score questionnaire shows good reliability and
      validity for both sexes, and it could be used as screening tool for lower urinary
      tract symptoms in any clinical setting or epidemiological investigation.

PMID- 24942905
TI  - Mercury accumulation in sharks from the coastal waters of southwest Florida.
AB  - As large long-lived predators, sharks are particularly vulnerable to exposure to
      methylmercury biomagnified through the marine food web. Accordingly, nonlethal
      means were used to collect tissues for determining mercury (Hg) concentrations
      and stable isotopes of carbon (delta(13)C) and nitrogen (delta(15)N) from a total
      of 69 sharks, comprising 7 species, caught off Southwest Florida from May 2010
      through June 2013. Species included blacknose (Carcharhinus acronotus), blacktip
      (C. limbatus), bull (C. leucas), great hammerhead (Sphyrna mokarran), lemon
      (Negaprion brevirostris), sharpnose (Rhizoprionodon terraenovae), and tiger
      sharks (Galeocerdo cuvier). The sharks contained Hg concentrations in their
      muscle tissues ranging from 0.19 mg/kg (wet-weight basis) in a tiger shark to
      4.52 mg/kg in a blacktip shark. Individual differences in total length and
      delta(13)C explained much of the intraspecific variation in Hg concentrations in
      blacknose, blacktip, and sharpnose sharks, but similar patterns were not evident
      for Hg and delta(15)N. Interspecific differences in Hg concentration were evident
      with greater concentrations in slower-growing, mature blacktip sharks and lower
      concentrations in faster-growing, young tiger sharks than other species. These
      results are consistent with previous studies reporting age-dependent growth rate
      can be an important determinant of intraspecific and interspecific patterns in Hg
      accumulation. The Hg concentrations observed in these sharks, in particular the
      blacktip shark, also suggested that Hg may pose a threat to shark health and
      fitness. 

PMID- 24942906
TI  - Clinical correlates of childhood trauma and dissociative phenomena in patients
      with severe psychiatric disorders.
AB  - In this present study, we aim to investigate the possibility of a link between
      psychotic disorders and traumatic experiences in a group of female patients
      diagnosed with psychotic disorders by comparing childhood trauma exposure with a
      group of non-psychotic psychiatric disorder attending the same pschiatric clinic.
      Secondary purpose of this study is to examine the clinical correlates of trauma
      exposure, dissociative phenomena and psychiatric symptomatology between these two
      group of patients. Two psychiatric sample groups, those with psychotic disorders
      mostly schizophrenic-(n = 54), and those with a non-psychotic severe psychiatric
      disorders (n = 24), were recruited. Data were collected for demographic,
      psychiatric and trauma histories and psychiatric symptomatology for all patients.
      In this study, high prevalance rates of childhood traumatic experiences and
      dissociative phenomena were found in both groups. Total scores of childhood
      trauma questionnaire in favor of the non-psychotic group were found to be close
      to significance (p = 0.052). DES scores of non-psychotic group were also higher
      although not statistically significant. 54.2 % of nonpsychotic cases had DES
      scores >20 on the other hand, that percentage of psychotic cases were found to be
      as 38.9 %. Furthermore, psychiatric patients who have suffered childhood
      traumatic experiences are far more likely to try to kill themselves than
      psychiatric patients who have not experienced such abuse. The high rates of
      childhood traumatic events in our present samples of both schizophrenia-spectrum
      patients and nonpsychotic patients confirm the need for clinicans to take trauma
      histories routinely.

PMID- 24942907
TI  - Predictors of suicide attempt status: acquired capability, ideation, and reasons.
AB  - The present study compared Non-Attempters, Recent Attempters, and Distant
      Attempters on the following three constructs: Acquired capability for suicide,
      reasons for attempting suicide (internal perturbation based reasons vs.
      extrapunitive/manipulative reasons), and suicidal ideation. Participants were 40
      Non-Attempters, 28 Recent Attempters, and 32 Distant Attempters at three state
      psychiatric hospitals. The sample consisted of 63 males and 37 females ranging in
      age from 18 to 63 years (M = 35.84, SD = 11.44). All patients completed the self
      report measures. There were significant differences between the groups on
      suicidal ideation and acquired capability for suicide. The results of the present
      study indicate that acquired capability and reasons for attempting suicide have
      considerable importance for understanding suicide risk. Integration of acquired
      capability for suicide and reasons for attempting suicide into assessment and
      treatment is warranted.

PMID- 24942909
TI  - In vivo assessment of a biological occluder for NOTES gastrotomy closure.
AB  - BACKGROUND: The objective of this study is to evaluate the closure of a
      transgastric natural orifice transluminal endoscopic surgery (NOTES) access using
      a multilayer extracellular matrix (ECM) occluder in a canine model. MATERIALS AND
      METHODS: Mongrel dogs (n = 4) underwent a transgastric NOTES peritoneoscopy and
      the gastrotomy was closed by deploying a 2-sided ECM occluder. Animals were
      killed at 7 days (n = 2) and 8 weeks (n = 2) for macroscopic and microscopic
      assessment. RESULTS: All procedures were completed without any complications. No
      air leaks were detected immediately after the procedure and at 48 hours
      postoperatively. At 7 days, ECM appeared to be resolved and mild mucosal
      inflammation was found at the site of gastrotomy. At 8 weeks, the gastrotomy site
      was macroscopically and microscopically covered with a normal-appearing gastric
      mucosa. There was an absence of inflammatory cells and no evidence of the ECM.
      CONCLUSION: The ECM occluder is safe and effective in this "proof-of-concept"
      preclinical model.

PMID- 24942910
TI  - Single-incision laparoscopic splenectomy for massive splenomegaly combining
      gastroesophageal devascularization using conventional instruments.
AB  - BACKGROUND: Single-incision laparoscopic splenectomy has been reported and was
      proved to be feasible and safe. Yet reports on single-incision laparoscopic
      surgery (SILS) for massive splenomegaly is not seen, neither is SILS for
      gastroesophageal devascularization; another correlated procedure for patients
      complicated with bleeding esophageal varices. From February 2011 to March 2012, 6
      male patients with a median age of 45.1 years (range, 25 to 65 y) who were
      diagnosed of liver cirrhosis, portal hypertension, splenomegaly, and
      hypersplenism underwent SILS by the same surgical team in our hospital. Of them,
      4 patients who were indicated had combined gastroesophageal devascularization,
      except for 1 conversion to hand-assisted laparoscopic approach because of
      bleeding, the operations were performed uneventfully and the surgical outcomes
      were satisfactory. Preoperative diagnosis was hypersplenism secondary to liver
      cirrhosis, the surgical outcome was satisfactory. This video, Supplemental
      Digital Content 1 and 2, http://links.lww.com/SLE/A104 and
      http://links.lww.com/SLE/A105 illustrates the crucial steps regarding the SILS
      for massive splenomegaly combined with gastroesophageal devascularization. The
      preoperative diagnosis are, hepatitis B, the patient's liver function is Liver
      Child-Pugh grade A. METHODS: The patient was placed in reverse Trendelenburg
      position, with the legs open. The surgeon was standing on the right side of the
      patient and an assistant standing in between the legs. One 20-mm incision was
      made under the umbilicus, a 10-mm Trocar (Johnson & Johnson Investment Co. Ltd.,
      NJ) was introduced in the middle of the incision, and the abdominal cavity was
      explored with a 10-mm, 30-degree scope (Storz Co. Ltd., Germany). Then a 12-mm
      and a 5-mm trocar were introduced through the same incision, respectively, 45
      degree to the 10-mm trocar at both sides to form a "?" shape. The procedure
      started with the dissection of the splenocolic ligament at the lower pole of the
      spleen, followed by creating a window by dissecting the gastrocolic ligament. The
      secondary branches of splenic pedicle were dissected and divided. The dissection
      of splenogastric ligament was continued along the gastric greater curvature, and
      short gastric vessels were encountered and divided. The left gastric artery was
      clipped and secured, followed by gastroesophageal devascularization along the
      cardiac to the esophagus 5 cm away from the esophagocardia junction, with
      Ligasure device. The splenic artery was identified, clipped, and divided. The
      splenic vein was finally divided followed by intraoperative autologous blood
      transfusion technique by collecting the blood from the distal splenic vein. The
      spleen was removed from the umbilical incision in a sample bag after being sliced
      into pieces. A drainage was placed through the incision. RESULTS: The operation
      was successful and the patient recovered well postoperatively: the operation time
      was 265 minutes, and the intraoperative blood loss was 300 mL. The postoperative
      course was uneventful and the patient was discharged 13 days later. CONCLUSIONS:
      SILS combining gastroesophageal devascularization for massive splenomegaly is
      technically feasible in the hands of surgeons with experiences of laparoscopic
      splenectomy. Indeed, the relative large scale of operation field for laparoscopic
      splenectomy makes the conflicts of instruments less practically challenging;
      however, techniques and sequences of the laparoscopic procedures should be
      modified to facilitate it, given the unavoidable constriction of movements for
      each instrument.

PMID- 24942908
TI  - Comparative transcriptomics of the model mushroom Coprinopsis cinerea reveals
      tissue-specific armories and a conserved circuitry for sexual development.
AB  - BACKGROUND: It is well known that mushrooms produce defense proteins and
      secondary metabolites against predators and competitors; however, less is known
      about the correlation between the tissue-specific expression and the target
      organism (antagonist) specificity of these molecules. In addition, conserved
      transcriptional circuitries involved in developing sexual organs in fungi are not
      characterized, despite the growing number of gene expression datasets available
      from reproductive and vegetative tissue. The aims of this study were: first, to
      evaluate the tissue specificity of defense gene expression in the model mushroom
      Coprinopsis cinerea and, second, to assess the degree of conservation in
      transcriptional regulation during sexual development in basidiomycetes. RESULTS:
      In order to characterize the regulation in the expression of defense loci and the
      transcriptional circuitries controlling sexual reproduction in basidiomycetes, we
      sequenced the poly (A)-positive transcriptome of stage 1 primordia and vegetative
      mycelium of C. cinerea A43mutB43mut. Our data show that many genes encoding
      predicted and already characterized defense proteins are differentially expressed
      in these tissues. The predicted specificity of these proteins with regard to
      target organisms suggests that their expression pattern correlates with the type
      of antagonists these tissues are confronted with. Accordingly, we show that the
      stage 1 primordium-specific protein CC1G_11805 is toxic to insects and nematodes.
      Comparison of our data to analogous data from Laccaria bicolor and Schizophyllum
      commune revealed that the transcriptional regulation of nearly 70 loci is
      conserved and probably subjected to stabilizing selection. A Velvet domain
      containing protein was found to be up-regulated in all three fungi, providing
      preliminary evidence of a possible role of the Velvet protein family in sexual
      development of basidiomycetes. The PBS-soluble proteome of C. cinerea primordia
      and mycelium was analyzed by shotgun LC-MS. This proteome data confirmed the
      presence of intracellular defense proteins in primordia. CONCLUSIONS: This study
      shows that the exposure of different tissues in fungi to different types of
      antagonists shapes the expression pattern of defense loci in a tissue-specific
      manner. Furthermore, we identify a transcriptional circuitry conserved among
      basidiomycetes during fruiting body formation that involves, amongst other
      transcription factors, the up-regulation of a Velvet domain-containing protein.

PMID- 24942911
TI  - Renal sodium transporters are increased in urinary exosomes of cyclosporine
      treated kidney transplant patients.
AB  - BACKGROUND/AIMS: Cyclosporine (CsA) is a calcineurin inhibitor widely used as an
      immunosuppressant in organ transplantation. Previous studies demonstrated the
      relationship between CsA and renal sodium transporters such as the Na-K-2Cl
      cotransporter in the loop of Henle (NKCC2). Experimental models of CsA-induced
      hypertension have shown an increase in renal NKCC2. METHODS: Using immunoblotting
      of urinary exosomes, we investigated in CsA-treated kidney transplant patients (n
      = 39) the excretion of NKCC2 and Na-Cl cotransporter (NCC) and its association
      with blood pressure (BP) level. We included 8 non-CsA-treated kidney transplant
      patients as a control group. Clinical data, immunosuppression and hypertension
      treatments, blood and 24-hour urine tests, and 24-hour ambulatory BP monitoring
      were recorded. RESULTS: CsA-treated patients tended to excrete a higher amount of
      NKCC2 than non-CsA-treated patients (mean +/- SD, 175 +/- 98 DU and 90 +/- 70.3
      DU, respectively; p = 0.05) and showed higher BP values (24-hour systolic BP 138
      +/- 17 mm Hg and 112 +/- 12 mm Hg, p = 0.003; 24-hour diastolic BP, 83.8 +/- 9.8
      mm Hg and 72.4 +/- 5.2 mm Hg, p = 0.015, respectively). Within the CsA-treated
      group, there was no correlation between either NKCC2 or NCC excretion and BP
      levels. This was confirmed by a further analysis including potential confounding
      factors. On the other hand, a significant positive correlation was observed
      between CsA blood levels and the excretion of NKCC2 and NCC. CONCLUSION: Overall,
      these results support the hypothesis that CsA induces an increase in NKCC2 and
      NCC in urinary exosomes of renal transplant patients. The fact that the increase
      in sodium transporters in urine did not correlate with the BP level suggests that
      in kidney transplant patients, other mechanisms could be implicated in CsA
      induced hypertension.

PMID- 24942912
TI  - D-dimer and risk of thromboembolic and bleeding events in patients with atrial
      fibrillation--observations from the ARISTOTLE trial.
AB  - BACKGROUND: D-dimer is related to adverse outcomes in arterial and venous
      thromboembolic diseases. OBJECTIVES: To evaluate the predictive value of D-dimer
      level for stroke, other cardiovascular events, and bleeds, in patients with
      atrial fibrillation (AF) treated with oral anticoagulation with apixaban or
      warfarin; and to evaluate the relationship between the D-dimer levels at baseline
      and the treatment effect of apixaban vs. warfarin. METHODS: In the ARISTOTLE
      trial, 18 201 patients with AF were randomized to apixaban or warfarin. D-dimer
      was analyzed in 14 878 patients at randomization. The cohort was separated into
      two groups; not receiving vitamin K antagonist (VKA) treatment and receiving VKA
      treatment at randomization. RESULTS: Higher D-dimer levels were associated with
      increased frequencies of stroke or systemic embolism (hazard ratio [HR] [Q4 vs.
      Q1] 1.72, 95% confidence interval [CI] 1.14-2.59, P = 0.003), death (HR [Q4 vs.
      Q1] 4.04, 95% CI 3.06-5.33) and major bleeding (HR [Q4 vs. Q1] 2.47, 95% CI 1.77
      3.45, P < 0.0001) in the no-VKA group. Similar results were obtained in the on
      VKA group. Adding D-dimer level to the CHADS2 score improved the C-index from
      0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for
      death, in the no-VKA group. D-dimer level improved the HAS-BLED score for
      prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641.
      There were no significant interactions between efficacy and safety of study
      treatment and D-dimer level. CONCLUSION: In anticoagulated patients with AF, the
      level of D-dimer is related to the risk of stroke, death, and bleeding, and adds
      to the predictive value of clinical risk scores. The benefits of apixaban were
      consistent, regardless of the baseline D-dimer level.

PMID- 24942914
TI  - Synthesis and photovoltaic performances in solution-processed BHJs of
      oligothiophene-substituted organocobalt complexes [(eta4-C4(nT)4)Co(eta5-C5H5)].
AB  - We describe an efficient synthetic route toward novel organocobalt complexes
      [(eta(4)-C4(nT)4)Co(eta(5)-C5H5)] with n = 1, 2, 3 thiophene rings. Solution
      processed bulk heterojunctions solar cells based on CpCoCb(3T)4:PCBM blends
      achieve power conversion efficiencies of up to 2.1%. 

PMID- 24942913
TI  - Insulin-like growth factor 1 treatment of MSCs attenuates inflammation and
      cardiac dysfunction following MI.
AB  - It has been reported that insulin-like growth factor 1 (IGF-1) promoted migration
      of endothelial cells and cardiac resident progenitor cells. In the previous
      study, we found the time-dependent and dose-dependent effects of IGF-1 treatment
      on the CXCR4 expression in MSCs in vitro, but it is still not clear whether IGF-1
      pretreatment of MSCs may play anti-apoptotic and anti-inflammation role in
      myocardial infarction. In this study, we demonstrated that IGF-1-treated MSCs'
      transplantation attenuate cardiac dysfunction, increase the survival of engrafted
      cells in the ischemic heart, decrease myocardium cells apoptosis, and inhibit
      protein production and gene expression of inflammation cytokines tumor necrosis
      factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6. IGF-1 pretreatment of
      MSCs may play anti-apoptotic and anti-inflammation roles in post-myocardial
      infarction. 

PMID- 24942915
TI  - The primary nitrate response: a multifaceted signalling pathway.
AB  - Nitrate (NO3(-)) application strongly affects gene expression in plants. This
      regulation is thought to be crucial for their adaptation in response to a
      changing nutritional environment. Depending on the conditions preceding or
      concomitant with nitrate provision, the treatment can affect up to a 10th of
      genome expression in Arabidopsis thaliana. The early events occurring after NO3(
      ) provision are often called the Primary Nitrate Response (PNR). Despite this
      simple definition, PNR is a complex process that is difficult to properly
      delineate. Here we report the different concepts related to PNR, review the
      different molecular components known to control it, and show, using meta
      analysis, that this concept/pathway is not monolithic. We especially bring our
      attention to the genome-wide effects of LBD37 and LBD38 overexpression, NLP7, and
      CHL1/NRT1.1 mutations.

PMID- 24942916
TI  - Vulnerability of coastal ecosystems to changes in harmful algal bloom
      distribution in response to climate change: projections based on model analysis.
AB  - Harmful algal blooms (HABs), those proliferations of algae that can cause fish
      kills, contaminate seafood with toxins, form unsightly scums, or detrimentally
      alter ecosystem function have been increasing in frequency, magnitude, and
      duration worldwide. Here, using a global modeling approach, we show, for three
      regions of the globe, the potential effects of nutrient loading and climate
      change for two HAB genera, pelagic Prorocentrum and Karenia, each with differing
      physiological characteristics for growth. The projections (end of century, 2090
      2100) are based on climate change resulting from the A1B scenario of the
      Intergovernmental Panel on Climate Change Institut Pierre Simon Laplace Climate
      Model (IPCC, IPSL-CM4), applied in a coupled oceanographic-biogeochemical model,
      combined with a suite of assumed physiological 'rules' for genera-specific bloom
      development. Based on these models, an expansion in area and/or number of months
      annually conducive to development of these HABs along the NW European Shelf
      Baltic Sea system and NE Asia was projected for both HAB genera, but no expansion
      (Prorocentrum spp.), or actual contraction in area and months conducive for
      blooms (Karenia spp.), was projected in the SE Asian domain. The implications of
      these projections, especially for Northern Europe, are shifts in vulnerability of
      coastal systems to HAB events, increased regional HAB impacts to aquaculture,
      increased risks to human health and ecosystems, and economic consequences of
      these events due to losses to fisheries and ecosystem services. 

PMID- 24942917
TI  - Mechanistic micro-structural theory of soft tissues growth and remodeling:
      tissues with unidirectional fibers.
AB  - A new mechanistic theory was developed for soft tissues growth and remodeling
      (G&R). The theory considers tissues with unidirectional fibers. It is based on
      the loading-dependent local turnover events of each constituent and on the
      resulting evolution of the tissue micro-structure, the tissue dimensions and its
      mechanical properties. The theory incorporates the specific mechanical properties
      and turnover kinetics of each constituent, thereby establishing a general
      framework which can serve for future integration of additional mechanisms
      involved in G&R. The feasibility of the theory was examined by considering a
      specific realization of tissues with one fibrous constituent (collagen fibers),
      assuming a specific loading-dependent first-order fiber's turnover kinetics and
      the fiber's deposition characteristics. The tissue was subjected to a continuous
      constant rate growth. Model parameters were adopted from available data. The
      resulting predictions show qualitative agreement with a number of well-known
      features of tissues including the fibers' non-uniform recruitment density
      distribution, the associated tissue convex nonlinear stress-stretch relationship,
      and the development of tissue pre-stretch and pre-stress states. These results
      show that mechanistic micro-structural modeling of soft tissue G&R based on first
      principles can successfully capture the evolution of observed tissues' structure
      and size, and of their associated mechanical properties. 

PMID- 24942926
TI  - Interferon controls SUMO availability via the Lin28 and let-7 axis to impede
      virus replication.
AB  - Small ubiquitin-related modifier (SUMO) protein conjugation onto target proteins
      regulates multiple cellular functions, including defence against pathogens,
      stemness and senescence. SUMO1 peptides are limiting in quantity and are thus
      mainly conjugated to high-affinity targets. Conjugation of SUMO2/3 paralogues is
      primarily stress inducible and may initiate target degradation. Here we
      demonstrate that the expression of SUMO1/2/3 is dramatically enhanced by
      interferons through an miRNA-based mechanism involving the Lin28/let-7 axis, a
      master regulator of stemness. Normal haematopoietic progenitors indeed display
      much higher SUMO contents than their differentiated progeny. Critically, SUMOs
      contribute to the antiviral effects of interferons against HSV1 or HIV.
      Promyelocytic leukemia (PML) nuclear bodies are interferon-induced domains, which
      facilitate sumoylation of a subset of targets. Our findings thus identify an
      integrated interferon-responsive PML/SUMO pathway that impedes viral replication
      by enhancing SUMO conjugation and possibly also modifying the repertoire of
      targets. Interferon-enhanced post-translational modifications may be essential
      for senescence or stem cell self-renewal, and initiate SUMO-dependent
      proteolysis. 

PMID- 24942927
TI  - Static Langer's line and wound contraction rates according to anatomical regions
      in a porcine model.
AB  - This study investigated wound contraction rates according to anatomical regions
      and wound morphology according to skin tension line in a micropig porcine model.
      Of the four animals used, skin tension morphology was determined in one pig. In
      the remaining three pigs, six pairs of full-thickness skin excisions were created
      on the dorsum (six square and six circular). The wounds were grouped, Wounds #1
      through #5, according to the skin tension line and anatomical regions: Wounds #1
      and #2, cephalic; Wounds #4 and #5, caudal; and Wound #3, center. Wound sizes and
      contraction rates were calculated for 28 days. A static tension topography of the
      micropig dorsum was obtained. Excisional wounds deformed along the local tension
      vector and healed in this fashion. Wound contraction rates were significantly
      higher for cephalic wounds (p = 0.004). No significant difference in wound
      contraction rates were observed between square and circular wounds. Final wound
      morphology was related to the local tension vector and initial wound shape.
      Cephalic wounds contracted more quickly. Further studies are needed to
      characterize scar formation after primarily closed surgical wounds in relation to
      the newly established skin tension topography and to elucidate the mechanism
      behind the variable wound contraction rates in the cephalocaudal gradient. 

PMID- 24942928
TI  - CdS nanorod arrays with TiO2 nano-coating for improved photostability and
      photocatalytic activity.
AB  - CdS nanorod arrays were grown on fluorine-doped tin oxide glass substrates via a
      hydrothermal process and subsequently coated with a TiO2 nanolayer via a vacuum
      dip-coating process to fabricate a one-dimensional array structured
      photocatalyst. The TiO2 nanolayer improved the photocatalytic efficiency of CdS
      nanorod arrays for the degradation of methylene blue due to the effective
      separation of the electron-hole pairs, and the photocorrosion of CdS nanorod
      arrays was successfully inhibited. 

PMID- 24942929
TI  - An indolocarbazole dimer as a new stereodynamic probe for chiral 1,2-diamines.
AB  - An indolocarbazole dimer that contains aldehyde groups at both ends was prepared
      by connecting two monomeric units through a rod-like 1,4-butadiynyl spacer. Upon
      mixing with chiral 1,2-diamines at room temperature, the dimer was in situ
      converted to the corresponding cyclic diimines in the presence of
      tetrabutylammonium acetate as a template. The resulting diimines fold to helical
      conformations of right-handed (P) or left-handed (M) orientations, depending on
      the absolute stereochemistries of chiral 1,2-diamines. The patterns and
      intensities of the CD spectra can be used to determine the absolute
      configurations and enantiomeric excesses of chiral 1,2-diamines. 

PMID- 24942930
TI  - Influence of family, friend and coworker social support and social undermining on
      weight gain prevention among adults.
AB  - OBJECTIVE: Examine longitudinal associations between sources of social support
      and social undermining for healthy eating and physical activity and weight
      change. METHODS: Data are from 633 employed adults participating in a cluster
      randomized multilevel weight gain prevention intervention. Primary predictors
      included social support and social undermining for two types of behaviors
      (healthy eating and physical activity) from three sources (family, friends, and
      coworkers) obtained via self-administered surveys. The primary outcome (weight in
      kg) was measured by trained staff. Data were collected at baseline, 12 months,
      and 24 months. Linear multivariable models examined the association of support
      and social undermining with weight over time, adjusting for intervention status,
      time, gender, age, education, and clustering of individuals within schools.
      RESULTS: Adjusting for all primary predictors and covariates, friend support for
      healthy eating (beta = -0.15), coworker support for healthy eating (beta = 
      0.11), and family support for physical activity (beta = -0.032) were associated
      with weight reduction at 24 months (P-values<0.05). Family social undermining for
      healthy eating was associated with weight gain at 24 months (beta = 0.12; P =
      0.0019). CONCLUSIONS: Among adult employees, friend and coworker support for
      healthy eating and family support for physical activity predicted improved weight
      management. Interventions that help adults navigate family social undermining of
      healthy eating are warranted.

PMID- 24942932
TI  - Growing up poor: a pediatric response.

PMID- 24942931
TI  - BDNF impairment is associated with age-related changes in the inner retina and
      exacerbates experimental glaucoma.
AB  - Brain-derived neurotrophic factor (BDNF) stimulation of its high-affinity
      receptor TrkB results in activation of pro-survival cell-signalling pathways that
      can afford neuroprotection to the retina. Reduction in retrograde axonal
      transport of neurotrophic factors such as BDNF from the brain to the neuronal
      cell bodies in the retina has been suggested as a critical factor underlying
      progressive and selective degeneration of ganglion cell layer and optic nerve in
      glaucoma. We investigated the role of BDNF in preserving inner retinal
      homeostasis in normal and glaucoma states using BDNF(+/-) mice and compared it
      with wild type controls. This study demonstrated that BDNF(+/-) animals were more
      susceptible to functional, morphological and molecular degenerative changes in
      the inner retina caused by age as well as upon exposure to experimental glaucoma
      caused by increased intraocular pressure. Glaucoma induced a down regulation of
      BDNF/TrkB signalling and an increase in levels of neurotoxic amyloid beta 1-42 in
      the optic nerve head which were exacerbated in BDNF(+/-) mice. Similar results
      were obtained upon analysing the human optic nerve head tissues. Our data
      highlighted the role of BDNF in maintaining the inner retinal integrity under
      normal conditions and the detrimental effects of its insufficiency on the retina
      and optic nerve in glaucoma. 

PMID- 24942933
TI  - Evaluation and disposition of Medicaid-insured children and adolescents with
      suicide attempts.
AB  - OBJECTIVE: Guidelines and quality of care measures for the evaluation of
      adolescent suicidal behavior recommend prompt mental health evaluation,
      hospitalization of high-risk youth, and specific follow-up plans-all of which may
      be influenced by sociodemographic factors. The aim of this study was to identify
      sociodemographic characteristics associated with variations in the evaluation of
      youth with suicidal behavior. METHODS: We conducted a large cohort study of
      youth, aged 7 to 18, enrolled in Tennessee Medicaid from 1995 to 2006, who filled
      prescriptions for antidepressants and who presented for evaluation of injuries
      that were determined to be suicidal on the basis of external cause-of-injury
      codes (E codes) and ICD-9-CM codes and review of individual medical records. Chi
      square tests and logistic regression were performed to assess the relationship
      between sociodemographic characteristics and documentation of mental health
      evaluation, hospitalization, and discharge instructions. RESULTS: Of 929 episodes
      of suicidal behavior evaluated in an acute setting, rural-residing youth were
      less likely to be admitted to a psychiatric hospital (adjusted odds ratio [AOR]
      0.72; 95% confidence interval [CI] 0.55-0.95) and more likely to be medically
      hospitalized only (AOR 1.92; 95% CI 1.39-2.65). Female subjects were less likely
      to be admitted to a psychiatric hospital (AOR 0.55; 95% CI 0.41-0.74) and more
      likely to be discharged home (AOR 1.44; 95% CI 1.01-2.04). Only 40% of those
      discharged to home had documentation of discharge instructions with both follow
      up provider and date. CONCLUSIONS: In this statewide cohort of youth with
      suicidal behavior, there were significant differences in disposition associated
      with sociodemographic characteristics.

PMID- 24942935
TI  - Spectroscopy and docking simulations of the interaction between lochnericine and
      bovine serum albumin.
AB  - Lochnericine (LOC) is a component of Voacanga africana, which is a type of
      traditional medical food in Africa widely used for treating diseases. In this
      article, the interaction between LOC and bovine serum albumin (BSA) was studied
      by fluorescence spectroscopy. Furthermore, Fourier transform infrared (FTIR),
      Raman and circular dichroism (CD) were used to investigate the structural changes
      of BSA. The experimental results consistently indicated that LOC changed the
      secondary structure of BSA. Three structure-similar components were used to study
      the interference experiments. The molecular modeling results showed that LOC
      could bind within not only sites I and II, but also bind the cavity of subdomain
      IB.

PMID- 24942934
TI  - Caregiver low health literacy and nonurgent use of the pediatric emergency
      department for febrile illness.
AB  - OBJECTIVE: To examine the association between caregiver health literacy and the
      likelihood of a nonurgent emergency department (ED) visit in children presenting
      for fever. METHODS: This cross-sectional study used the Newest Vital Sign to
      assess the health literacy of caregivers accompanying children with fever to the
      ED. Visit urgency was determined by resources utilized during the ED visit.
      Findings were stratified by race and child age. Chi-square and logistic
      regression analysis controlling for race were conducted to determine the
      association between low health literacy and ED visit urgency. RESULTS: A total of
      299 caregivers completed study materials. Thirty-nine percent of ED visits for
      fever were nonurgent, and 63% of caregivers had low health literacy. Low health
      literacy was associated with a higher proportion of nonurgent ED visits for fever
      (44% vs 31%, odds ratio 1.8, 95% confidence interval [CI] 1.1, 2.9). Low health
      literacy was associated with higher odds of a nonurgent visit in white and
      Hispanic caregivers but not in black caregivers. In regression analysis, children
      >= 2 years old had higher odds of a nonurgent visit if caregivers had low health
      literacy (adjusted odds ratio 2.0; 95% CI 1.1, 4.1); this relationship did not
      hold for children <2 years old (adjusted odds ratio 0.8; 95% CI 0.4, 1.8).
      CONCLUSIONS: Nearly two-thirds of caregivers with their child in the ED for fever
      have low health literacy. Caregiver low health literacy is associated with
      nonurgent ED utilization for fever in children over 2 years of age. Future
      interventions could target health literacy skills regarding fever in caregivers
      of children >= 2 years.

PMID- 24942937
TI  - Immunoproteomics of processed beef proteins reveal novel galactose-alpha-1,3
      galactose-containing allergens.
AB  - BACKGROUND: Red meat allergy presents a novel form of food allergy with severe
      delayed allergic reactions where IgE antibodies are directed against the
      carbohydrate alpha-Gal epitope. Food preparation and processing can influence the
      allergenicity of proteins. The aim of this study was to characterize the
      proteomic profile of different beef preparations and to investigate their alpha
      Gal reactivity and potential allergenicity. METHODS: Extracts from raw, boiled,
      fried, and medium rare prepared beef were assessed by 2D PAGE for the comparison
      of protein profiles. IgE-binding proteins were identified using immunoblot
      coupled proteomic analysis using sera from red meat-allergic patients. Presence
      of the alpha-Gal epitope was verified using anti-alpha-Gal antibody and IgE
      inhibition immunoblot with alpha-Gal. RESULTS: Multiple IgE-binding proteins were
      detected in the different beef preparations, many of which were also recognized
      by the anti-alpha-Gal antibody. Protein spots reacting with IgE in patient sera
      were analyzed by MS/MS, resulting in identification of 18 proteins with high
      identification scores. Seven of the 18 beef allergens identified using meat
      allergic patient sera were also recognized by the anti-alpha-Gal monoclonal
      antibody, and four of them were stabile to thermal treatment. Furthermore, a dose
      dependent inhibition of red meat-allergic patients' IgE to beef by alpha-Gal was
      demonstrated. CONCLUSIONS: We show that the alpha-Gal epitope is commonly present
      in IgE-reactive beef proteins recognized by meat-allergic patients. Seven novel
      alpha-Gal-containing IgE-binding proteins were identified, of which four were
      stable to heat treatment. Thus, the allergenicity of red meat proteins is
      preserved even upon different thermal cooking.

PMID- 24942940
TI  - Indolent B-cell lymphoma: the current standard in 2014.

PMID- 24942938
TI  - Quantification of gross tumour volume changes between simulation and first day of
      radiotherapy for patients with locally advanced malignancies of the lung and
      head/neck.
AB  - INTRODUCTION: To quantify changes in gross tumour volume (GTV) between simulation
      and initiation of radiotherapy in patients with locally advanced malignancies of
      the lung and head/neck. METHODS: Initial cone beam computed tomography (CT) scans
      from 12 patients with lung cancer and 12 with head/neck cancer (head and neck
      squamous cell carcinoma (HNSCC)) treated with intensity-modulated radiotherapy
      with image guidance were rigidly registered to the simulation CT scans. The GTV
      was demarcated on both scans. The relationship between percent GTV change and
      variables including time interval between simulation and start, tumour (T) stage,
      and absolute weight change was assessed. RESULTS: For lung cancer patients, the
      GTV increased a median of 35.06% (range, -16.63% to 229.97%) over a median
      interval of 13 days (range, 7-43), while for HNSCC patients, the median GTV
      increase was 16.04% (range, -8.03% to 47.41%) over 13 days (range, 7-40). These
      observed changes are statistically significant. The magnitude of this change was
      inversely associated with the size of the tumour on the simulation scan for lung
      cancer patients (P < 0.05). However, the observed changes in GTV did not
      correlate with the duration of the interval for either disease site. Similarly, T
      stage, absolute weight change and histologic type (the latter for lung cancer
      cases) did not correlate with degree of GTV change (P > 0.1). CONCLUSION: While
      the observed changes in GTV were moderate from the time of simulation to start of
      radiotherapy, these findings underscore the importance of image guidance for
      target localisation and verification, particularly for smaller tumours.
      Minimising the delay between simulation and treatment initiation may also be
      beneficial.

PMID- 24942936
TI  - Medical management of metastatic medullary thyroid cancer.
AB  - Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer that
      occurs in both heritable and sporadic forms. Discovery that mutations in the
      rearranged during transfection (RET) proto-oncogene predispose to familial cases
      of this disease has allowed for presymptomatic identification of gene carriers
      and prophylactic surgery to improve the prognosis of these patients. A
      significant number of patients with the sporadic type of MTC and even those with
      familial disease still present with lymph node or distant metastases, making
      surgical cure difficult. Over the past several decades, many different types of
      therapy for metastatic disease have been attempted with limited success. Improved
      understanding of the molecular defects and pathways involved in both familial and
      sporadic MTC has resulted in new hope for these patients with the development of
      drugs targeting the specific alterations responsible. This new era of targeted
      therapy with kinase inhibitors represents a significant step forward from
      previous trials of chemotherapy, radiotherapy, and hormone therapy. Although much
      progress has been made, additional agents and strategies are needed to achieve
      durable, long-term responses in patients with metastatic MTC. This article
      reviews the history and results of medical management for metastatic MTC from the
      early 1970s up until the present day.

PMID- 24942941
TI  - Pathology of follicular lymphoma.
AB  - Follicular lymphoma (FL) is a heterogeneous disease, and there are many different
      subgroups, such as in terms of age of onset, involved organ (especially
      extranodal sites such as gastrointestinal tract) and genetic abnormality. Grade
      3B is currently regarded as a distinct entity by molecular genetic analyses, but
      the independence of Grade 3A remains unclear. Variations of clinical course are
      known in FL. Some cases are very indolent, but others are not. The latter cases
      show histological transformation to diffuse large B-cell lymphoma (DLBCL) (high
      grade transformation) and an aggressive course. Histological transformation to
      DLBCL is reported to occur in about 30-40% of patients, at a rate of about 3%
      each year. However, it reaches a plateau at about 16 years, so the stratification
      of patients in whom transformation would or would not occur is very important for
      the therapeutic strategy. From genome-wide analysis by next-generation
      sequencing, EZH2, CREBBP and MLL2, which are histone-modifying genes, have been
      shown to be frequently mutated in FL and to have an important role in
      lymphomagenesis. IGH-BCL2 translocation and CREBBP mutations are early events,
      whereas MLL2 and TNFSFR14 mutations represent late events during disease
      evolution. In the 2008 WHO classification, three new variants: (1) pediatric
      follicular lymphoma, (2) primary intestinal follicular lymphoma and (3) in situ
      follicular lymphoma, are included. Pathologists and clinicians should consider
      these new developments when deciding on the diagnostic and therapeutic strategy.

PMID- 24942939
TI  - Primary hyperparathyroidism with pancreatitis: experience of management in 5
      patients with review of literature.

PMID- 24942942
TI  - Pathology of indolent B-cell neoplasms other than follicular lymphoma.
AB  - Indolent B-cell lymphomas include follicular lymphoma (FL), chronic lymphocytic
      leukemia/small lymphocytic lymphoma (CLL/SLL) and marginal zone lymphomas (MZLs).
      They are a diverse group of disorders with different clinical, morphological,
      immunophenotypic and genetic features. However, because of several histological
      similarities, such as in cell size and nodular structure, it may sometimes be
      difficult to differentiate them and to make a definitive diagnosis. In this
      review article, we summarize the histopathology of indolent B-cell neoplasms
      excluding FL and including hairy cell leukemia, and briefly mention recent
      genetic findings useful for their differential diagnosis. In addition, a
      provisional subtype of low-grade B-cell lymphoma,
      "prolymphocytic/paraimmunoblastic lymphoma", is described.

PMID- 24942943
TI  - Molecular pathogenesis of follicular lymphoma.
AB  - t(14;18) translocation has been recognized as a genetic hallmark of follicular
      lymphoma (FL), but it is now known that additional genetic aberrations are
      required for the development of FL. With recent advances in the technology for
      DNA analysis, recurrent gene aberrations such as TNFRSF14, EPHA7, EZH2, CREBBP,
      EP300, MLL2 and MEF2B have been identified. A few t(14;18)-positive B cells can
      be detected in healthy individuals, and these B cells are reported to have their
      own biological features that are closely associated with the pathogenesis of FL.
      On the other hand, FL is characterized by a unique microenvironment. Further
      understanding of the pathogenesis of FL is expected to contribute to the
      development of novel treatment approaches for this disease.

PMID- 24942944
TI  - Treatment of follicular lymphoma.
AB  - Follicular lymphoma (FL) is the most common subtype of indolent lymphomas.
      Several lines of evidence suggest that the prognosis of patients with FL has
      improved since the introduction of rituximab, although cure cannot be achieved.
      Although the treatment paradigm for FL has changed over the past decade with the
      introduction of rituximab and other agents, there is still no standard therapy to
      fit all patients. Instead, treatment decisions are made taking into consideration
      disease status (stage, tumor burden, and presence of symptoms) and patient
      factors including patient preferences. Rituximab-containing chemotherapy such as
      R-CHOP, R-CVP, and bendamustine plus rituximab is usually recommended for
      symptomatic patients. However, optimal rituximab-containing chemotherapy has not
      been established. Rituximab maintenance is one of the post-induction options for
      patients responding to first-line chemoimmunotherapy. For patients without
      symptoms and low-tumor burden, both expectant management (watchful waiting) and
      rituximab monotherapy are reasonable options. A very limited proportion of
      patients with FL are diagnosed at stage I with rigorous staging using bone marrow
      biopsy and whole-body imaging with computed tomography (CT) and/or positron
      emission tomography/CT. Although local radiotherapy has been the standard
      approach for these patients, its role is being questioned. Patients with FL who
      achieve remission eventually relapse and require salvage therapy. The salvage
      regimen should be chosen taking into account previous treatment and its response
      duration. Moreover, the presence of histological transformation should be
      assessed.

PMID- 24942945
TI  - Hematopoietic stem cell transplantation for follicular lymphoma: optimal timing
      and indication.
AB  - The definitive management of advanced follicular lymphoma (FL) remains
      controversial due to various treatment options, including watchful waiting,
      single-agent or combination chemotherapy, monoclonal antibody, and
      radioimmunotherapy. These options can provide prolonged progression-free
      survival. However, they cannot cure advanced FL. Allogeneic hematopoietic stem
      cell transplantation (allo-SCT) remains the sole curative therapy for FL. Allo
      SCT has had a major impact with the use of reduced-intensity conditioning
      regimens because of its lower associated nonrelapse mortality compared with
      myeloablative regimens. Autologous SCT (auto-SCT) shows high response rates and
      extends progression-free survival in patients with chemosensitive relapse. In the
      rituximab era, however, associated comorbidities, risk of secondary cancers, and
      presence of refractory disease have become problematic in the auto-SCT
      population. On the basis of results from large-scale randomized trials, upfront
      auto-SCT is not recommended. Novel conditioning regimens including
      radioimmunotherapy followed by either auto-SCT or allo-SCT are likely to show
      efficacy even in chemorefractory disease. Consequently, the optimal timing for
      SCT remains a matter of opinion, except for patients in first remission. However,
      the outcomes of allo-SCT and auto-SCT keep on improving. Physicians should note
      that there is no therapy with a track record equivalent to that of SCT for
      relapsed or refractory FL.

PMID- 24942946
TI  - The role of tumor-associated macrophages on serum soluble IL-2R levels in B-cell
      lymphomas.
AB  - Interkeukin-2 receptor (IL-2R) is comprised of three different subunits (alpha,
      beta, and gamma chain) and is expressed on B cells and NK cells besides T cells.
      CD25 is also known as the IL-2Ralpha chain on cell membranes, while soluble IL-2R
      (sIL-2R) is generated by the proteolytic cleavage of the IL-2Ralpha chain. Levels
      of sIL-2R in sera are monitored as a marker of disease activity in patients with
      lymphoma. However, elevated serum sIL-2R levels are also found in inflammatory
      diseases, such as infectious diseases. Levels of sIL-2R in sera are thought to
      reflect tumor burden in adult T-cell leukemia/lymphoma due to the expression of
      CD25 on tumor cells. Conversely, sIL-2R is thought to be mainly derived from
      activated T cells infiltrating tumor tissues in diffuse large B-cell lymphoma
      (DLBCL) and follicular lymphoma (FL) because lymphoma cells except for a subtype
      of DLBCL are mainly negative for CD25. Matrix metalloproteinase-9, a protease
      capable of cleaving the membrane bound IL-2Ralpha chain, is mainly produced by
      tissue-associated macrophages. Increased macrophages in tumor tissues are
      reported to be associated with poor prognosis, especially in Hodgkin's lymphoma.
      We found increased macrophages in DLBCL and FL compared with reactive lymphoid
      hyperplasia as well as a positive correlation between the levels of sIL-2R in
      sera and the number of macrophages in tumor tissues in FL and extranodal DLBCL.

PMID- 24942947
TI  - Role of CD204-positive tumor-associated macrophages in adult T-cell
      leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is endemic in southwestern Japan, the
      Caribbean basin, and parts of central Africa, and is considered to be caused by
      long-term infection with human T-cell leukemia virus type I. CD204 is a scavenger
      receptor that is overexpressed on alternatively activated macrophages and is
      known to be overexpressed in tumor-associated macrophages (TAMs). CD206 is also
      considered a marker of alternatively activated macrophages. However, no studies
      have investigated CD206 and TAMs. In the present study, we investigated the
      significance of CD204(+) and CD206(+) TAMs in ATLL tissue samples. We also
      investigated the correlations with the Ki-67 labeling index (Ki-67LI) and the
      number of CD31(+) vessels. We found that the number and ratio of CD204(+) TAMs
      were closely associated with the Ki-67LI, which reflects lymphoma cell
      proliferation. The number of CD31(+) vessels was not correlated with the number
      or ratio of CD204(+) and CD206(+) TAMs. The number and ratio of CD204(+) and
      CD206(+) TAMs, number of CD31(+) vessels, and the Ki-67LI were not associated
      with the clinical outcome of patients with ATLL. Although further studies are
      necessary to uncover the detailed mechanisms of CD204 and lymphoma proliferation,
      these data may provide novel insight into the pathogenesis of ATLL.

PMID- 24942948
TI  - Distinct global DNA methylation status in B-cell lymphomas: immunohistochemical
      study of 5-methylcytosine and 5-hydroxymethylcytosine.
AB  - Lymphomas are malignant neoplasms composed of lymphoid cells at various
      developmental stages and lineages. Recent advances in comprehensive genomic
      analyses in acute myeloid leukemia have revealed prevalent mutations in
      regulators of epigenetic phenomena including global DNA methylation status. The
      examples include mutations in isocitrate dehydrogenase 1 (IDH1), IDH2, and ten
      eleven translocation 2. These mutations are proposed to inhibit conversion of 5
      methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), leading to global
      accumulation of 5 mC. These changes in global DNA methylation status can be
      visualized immunohistochemically using specific antibodies against 5 mC and 5
      hmC. We examined the global DNA methylation status of B-cell lymphomas and that
      of their normal counterparts by immunohistochemistry for 5 mC and 5 hmC. Non
      tumor lymphoid cells inside germinal centers (GC) in reactive lymphoid
      hyperplasia (RLH) were stained positive for 5 mC, but they were negative for 5
      hmC. Similarly, follicular lymphomas, whose postulated normal counterparts are
      centrocytes in GCs, were 5 mC-positive but 5 hmC-negative by
      immunohistochemistry. This immunostaining pattern was also observed in Burkitt
      lymphoma. In contrast, non-tumor lymphoid cells in mantle zones were stained
      positive for 5 mC as well as for 5 hmC. Likewise, most mantle cell lymphomas,
      whose postulated normal counterparts are mantle zone B cells in RLH, were stained
      positive for 5 mC as well as for 5 hmC. This immunostaining pattern was also
      observed in chronic lymphocytic leukemia/small lymphocytic lymphoma. These
      results suggest that, in terms of 5 mC/5 hmC immunohistochemistry, B-cell
      lymphomas with different histological subtypes are associated with distinct
      global DNA methylation statuses that resemble those of their postulated normal
      counterparts.

PMID- 24942949
TI  - Tumor microenvironment and RIG-I signaling molecules in Epstein Barr virus
      positive and -negative classical Hodgkin lymphoma of the elderly.
AB  - Classical Hodgkin lymphoma (CHL) is a B-cell neoplasm characterized by Hodgkin
      and Reed-Sternberg (HRS) cells. Its prevalence exhibits a bimodal pattern of
      peaking in young adults and the elderly. There is an association with Epstein
      Barr virus (EBV) infection in about 50% of cases of CHL of the elderly, and the
      outcome of these patients is unfavorable. It is not well known how the latent
      infection of EBV is involved in the pathophysiology of CHL of the elderly. To
      address this issue, we examined the tumor microenvironment (TME) and the
      expression of molecules related to EBV infection in HRS cells in 10 EBV-positive
      CHL and 7 EBV-negative CHL patients older than 50 years. In EBV-positive CHL, we
      found an increased population of FOXP3(+) cells, while that of granzyme B(+)
      cells was reduced, compared with those in EBV-negative CHL. The expression of
      inhibitory chemokine CCL20 was increased in EBV-positive HRS cells compared with
      that in EBV-negative HRS cells. In addition, despite increased expression of a
      pattern recognition receptor, RIG-I, in intracellular innate immunity, there was
      no evidence of interferon regulatory factor 3 activation or interferon-beta
      induction in EBV-positive HRS cells in CHL of the elderly. The disease recurred
      frequently (50%) in EBV-positive CHL. The current study thus suggests the
      possibility that the latent infection of EBV alters the expression of chemokines
      and the innate immunity response in HRS cells and modulates TME to an
      immunosuppressive state, which may account for the unfavorable disease course in
      CHL of the elderly.

PMID- 24942950
TI  - Elevated plasma fibrinogen in clinically asymptomatic unicentric Castleman's
      disease: a case report.
AB  - This is the first report of an early association between elevated fibrinogen and
      asymptomatic unicentric Castleman's disease (CD). A 49-year-old asymptomatic
      female who was serving as a normal control in an unrelated study was incidentally
      found to have significantly elevated levels of plasma fibrinogen. Upon further
      investigation with computer tomography scans and magnetic resonance imaging, the
      woman was found to have a mobile mass in the abdominal region which was
      surgically removed. Based on histological analysis, a diagnosis of CD was made.
      At four-month follow-up, no additional signs of CD were present and fibrinogen
      levels returned to the normal range. This report, therefore, signifies the
      importance for physicians to consider unicentric CD in the differential diagnosis
      when patients present with elevated levels of plasma fibrinogen. Awareness of
      this diagnostic possibility may lead to increased early diagnosis of CD before
      symptoms become apparent, and provide a marker candidate for CD activity that may
      assist in monitoring treatment success.

PMID- 24942951
TI  - Treatment of multiple myeloma in Akita: features and outcomes in the era of novel
      agents.

PMID- 24942952
TI  - HbA1c is a reliable test for type 2 diabetes in primary care irrespective of
      chronic kidney disease.

PMID- 24942953
TI  - Modulating supramolecular helicity and electrical conductivity of perylene dyes
      through an achiral alkyl chain.
AB  - Here we have shown that it is possible to modulate hydrophobic and hydrophilic
      interactions to further adjust the supramolecular helicity by changing the length
      of an alkyl chain. These modulated supramolecular interactions have been
      translated to and observed in electrical conductivity, and provide a new pathway
      to construct a high-performance nanodevice. 

PMID- 24942954
TI  - A prospective, randomized, controlled, exploratory study of comprehensive dietary
      advice in ulcerative colitis: impact on disease activity and quality of life.
AB  - OBJECTIVES: The impact of food on relapse in ulcerative colitis has not been
      clearly defined. The aim of this prospective, randomized-controlled study was to
      evaluate the impact of comprehensive dietary guidelines on the clinical course of
      the disease and quality of life in patients with ulcerative colitis. MATERIALS
      AND METHODS: Patients were allocated randomly to an intervention or a control
      group. Participants in the intervention group were provided dietary guidelines in
      the form of an educational booklet that was recommended for use for 4-6 weeks
      during disease flare, that patients eat little and often (four to six times a
      day), drink adequate fluids, decrease excess intake of fat, decrease simple
      carbohydrates and decrease high-fibre foods during flare.Validated and study
      designed questionnaires were used to compare patients' perceived quality of life,
      colitis activity scores and eating habits before and following the dietary advice
      provided. RESULTS: Overall, 112 patients completed the study. Study participants
      were asked to complete the Inflammatory Bowel Disease Questionnaire and Simple
      Clinical Colitis Activity Index together with the Food Frequency Questionnaire at
      0, 6 and 24 weeks. At 24 weeks, there was a mean reduction in the Simple Clinical
      Colitis Activity Index score in the intervention group compared with an increase
      in the score in the control group [-1.304 (P=0.0108) vs. 0.875 (P=0.0249)]. There
      was a mean increase in the Inflammatory Bowel Disease Questionnaire score in the
      intervention group compared with a reduction in the score in the control group
      [7.17 (P=0.126) vs. -3.44 (P=0.205)]. A total of 69% of patients in the
      intervention group found the dietary advice significantly or moderately helpful.
      CONCLUSION: The study suggests that there is likely to be a link between the
      dietary advice provided and symptomatic improvement. The effect of diet may not
      occur through the addition or the elimination of single nutrients; rather, each
      food consumed combines many nutrients that allow for a synergistic or an
      antagonistic action when present in a certain composition.

PMID- 24942955
TI  - Clostridium difficile infection in hospitalized patients at a Czech tertiary
      center: analysis of epidemiology, clinical features, and risk factors of
      fulminant course.
AB  - OBJECTIVE: Clostridium difficile infection (CDI) has been increasing in
      incidence, with significant morbidity and mortality, and is subject to
      geographical and institutional variability. We aimed to characterize epidemiology
      and clinical manifestations of CDI in a Czech tertiary care center and to
      identify risk factors of fulminant course. METHODS: All adult patients
      hospitalized with primary CDI in a 3-year period were retrospectively identified.
      Epidemiological and clinically descriptive data were extracted from medical
      records. Multivariate analysis was used to identify the risk factors of fulminant
      course. The relationship between incidence of CDI and antibiotic consumption was
      evaluated. RESULTS: Overall, 183 CDI patients, median age 67 years, were
      enrolled. Hospital-acquired CDI was present in 85% of cases. The incidence of CDI
      was 1/10,000 patient-days. Hospital-acquired CDI hospital mortality was 22.4%.
      Severe CDI (SCDI) was identified in 15.8% of patients, with 62% mortality. SCDI
      patients had longer onset of symptoms to diagnosis interval compared with mild
      CDI (P=0.05). Multivariate analysis showed that SCDI patients were older
      (P=0.018), and more frequently had abnormal abdominal physical findings
      (P=0.001), higher inflammatory markers (P<0.001), higher creatinine (P=0.002),
      and lower albumin (P<0.001) than patients with mild CDI. Analysis of antibiotic
      consumption at departments with the highest incidence of CDI showed a trend
      toward higher incidence of CDI associated with penicillin use (P=0.08) and a
      negative correlation of CDI incidence with nitroimidazoles consumption (P=0.03).
      CONCLUSION: CDI is less frequent in the conditions studied compared with literary
      data; however, the fulminant form has a very high mortality. Delayed recognition
      and treatment is a crucial determinant of the severity of CDI. The association
      between CDI and antibiotic consumption is less clear.

PMID- 24942956
TI  - Impaired suppressive capacity of activation-induced regulatory B cells in
      systemic lupus erythematosus.
AB  - OBJECTIVE: B cells with immunoregulatory properties (Breg cells) have been
      described in mice, but their role in the control of human immune responses is not
      well defined. We recently identified a human population of activated FSC(high) B
      cells that exhibited regulatory activity toward T helper cells. The aim of the
      present study was to test such induced Breg (iBreg) cells in patients with
      autoimmune disease. METHODS: Purified CD19+FSC(high) B cells derived from
      patients with systemic lupus erythematosus (SLE) or from healthy donors, which
      were activated via their B cell receptor, were cocultured with CD3-stimulated
      CD4+ T helper cells from SLE patients or healthy donors. (3) H-thymidine
      incorporation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were
      used to analyze proliferation, cytokine secretion, and surface marker expression.
      RESULTS: Although under costimulatory conditions, FSC(high) SLE B cells supported
      the proliferation of healthy donor T cells to a similar extent as donor B cells,
      their regulatory function was significantly diminished in B cell suppressor
      assays. Similar effects were seen when SLE T cells were used, confirming that SLE
      T cells were equally susceptible to iBreg cell signals as healthy donor T cells
      and that SLE iBreg cell defects were independent of T cell origin. B cell
      viability and expression of surface markers (CD25, CD80, and B7-H1) or cytokines
      (interleukin-6 [IL-6], tumor necrosis factor alpha, and IL-10) were comparable in
      the two B cell populations. There was no correlation between the extent of iBreg
      cell-induced inhibition and disease activity. CD19+FSC(high) B cells from
      patients with another systemic autoimmune disease, granulomatosis with
      polyangiitis (Wegener's) (GPA), exhibited no regulatory defects, which suggests
      that the iBreg cell defects were SLE-specific and not a general consequence of
      autoimmunity or inflammation. CONCLUSION: Induced Breg cells from SLE patients,
      but not GPA patients, are less effective in the control of T helper cell
      proliferation, which supports the reported skewed B cell repertoire in SLE. The
      malfunctioning SLE iBreg cells might allow the overstimulation of immune
      responses and contribute to the initiation and/or perpetuation of disease.

PMID- 24942957
TI  - Systematic review: the treatment of muscle cramps in patients with cirrhosis.
AB  - BACKGROUND: Up to 88% of patients with hepatic cirrhosis experience painful
      muscle cramps resulting in sleep deprivation and impaired quality of life.
      Management is often based on poor evidence with varying degrees of success in
      controlling the frequency and severity of muscle cramps in this group. AIM: To
      review systematically the treatment options for muscle cramps in cirrhosis.
      METHODS: A systematic review of the relevant databases to identify treatments for
      muscle cramps in patients with hepatic cirrhosis was performed. Studies meeting
      the selection criteria were reviewed and quality of the papers was rated using a
      validated quality rating scale. The results for each treatment are reported.
      RESULTS: Eighteen publications were identified as eligible for inclusion in this
      systematic review. The majority (n = 15) of these were treatment/intervention
      reports. Only three randomised-control studies were identified. A wide range of
      treatments were identified including zinc, 1-alpha-hydroxy vitamin D, vitamin E,
      branched chain amino acids, taurine, l-carnitine, nuiche-shen-qi-wen, eperisone
      hydrochloride, intravenous albumin and quinidine. There were some reported
      improvements in muscle cramps with most interventions with the exception of
      vitamin E but the evidence predominantly relies on case study reports. There is a
      lack of randomised-controlled clinical studies to support using these
      interventions. CONCLUSIONS: There appear to be a number of promising treatments
      for muscle cramps in cirrhosis. However, there remains a need for further double
      blinded, randomised, controlled clinical investigations to support routine use of
      these interventions to treat muscle cramps in patients with hepatic cirrhosis.

PMID- 24942958
TI  - Structures of bacterial kynurenine formamidase reveal a crowded binuclear zinc
      catalytic site primed to generate a potent nucleophile.
AB  - Tryptophan is an important precursor for chemical entities that ultimately
      support the biosynthesis of key metabolites. The second stage of tryptophan
      catabolism is catalysed by kynurenine formamidase, an enzyme that is different
      between eukaryotes and prokaryotes. In the present study, we characterize the
      catalytic properties and present the crystal structures of three bacterial
      kynurenine formamidases. The structures reveal a new amidase protein fold, a
      highly organized and distinctive binuclear Zn2+ catalytic centre in a confined,
      hydrophobic and relatively rigid active site. The structure of a complex with 2
      aminoacetophenone delineates aspects of molecular recognition extending to the
      observation that the substrate itself may be conformationally restricted to
      assist binding in the confined space of the active site and for subsequent
      processing. The cations occupy a crowded environment, and, unlike most Zn2+
      dependent enzymes, there is little scope to increase co-ordination number during
      catalysis. We propose that the presence of a bridging water/hydroxide ligand in
      conjunction with the placement of an active site histidine supports a distinctive
      amidation mechanism. 

PMID- 24942961
TI  - CORR Insights(r): what is the use of imaging before referral to an orthopaedic
      oncologist? A prospective, multicenter investigation.

PMID- 24942960
TI  - The alpha-defensin test for periprosthetic joint infection outperforms the
      leukocyte esterase test strip.
AB  - BACKGROUND: Synovial fluid biomarkers have demonstrated diagnostic accuracy
      surpassing the currently used diagnostic tests for periprosthetic joint infection
      (PJI). QUESTIONS/PURPOSES: The purpose of this study is to directly compare the
      sensitivity and specificity of the synovial fluid alpha-defensin immunoassay to
      the leukocyte esterase (LE) colorimetric test strip. METHODS: Synovial fluid was
      collected from 46 patients meeting the inclusion criteria of this prospective
      diagnostic study. Synovial fluid samples were tested with both a novel synovial
      fluid-optimized immunoassay for alpha-defensin and the LE colorimetric test
      strip. The Musculoskeletal Infection Society (MSIS) definition was used to
      classify 23 periprosthetic infections and 23 aseptic failures; this
      classification was used as the standard against which the two diagnostic tests
      were compared. RESULTS: The synovial fluid alpha-defensin immunoassay correctly
      predicted the MSIS classification of all patients in the study, demonstrating a
      sensitivity and specificity of 100% for the diagnosis of PJI. The alpha-defensin
      assay could be read for all samples, including those with blood in the synovial
      fluid. The leukocyte esterase test strip could not be interpreted in eight of 46
      samples (17%) as a result of blood interference. Analysis of the LE strips that
      could be interpreted yielded a sensitivity of 69% and a specificity of 100%.
      CONCLUSIONS: The synovial fluid alpha-defensin immunoassay outperformed the LE
      colorimetric test strip in this study and provided reliable results even when the
      LE test strip failed as a result of blood interference. The simple analytic
      results provided by the alpha-defensin immunoassay, compared with the more
      complex and interpretive nature of both the MSIS criteria and LE colorimetric
      test strip, make it a highly attractive diagnostic tool. LEVEL OF EVIDENCE: Level
      II, diagnostic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 24942959
TI  - Arthroscopic Bristow-Latarjet combined with bankart repair restores shoulder
      stability in patients with glenoid bone loss.
AB  - BACKGROUND: Arthroscopic Bankart repair alone cannot restore shoulder stability
      in patients with glenoid bone loss involving more than 20% of the glenoid
      surface. Coracoid transposition to prevent recurrent shoulder dislocation
      according to Bristow-Latarjet is an efficient but controversial procedure.
      QUESTIONS/PURPOSES: We determined whether an arthroscopic Bristow-Latarjet
      procedure with concomitant Bankart repair (1) restored shoulder stability in this
      selected subgroup of patients, (2) without decreasing mobility, and (3) allowed
      patients to return to sports at preinjury level. We also evaluated (4) bone block
      positioning, healing, and arthritis and (5) risk factors for nonunion and
      coracoid screw pullout. METHODS: Between July 2007 and August 2010, 79 patients
      with recurrent anterior instability and bone loss of more than 20% of the glenoid
      underwent arthroscopic Bristow-Latarjet-Bankart repair; nine patients (11%) were
      either lost before 2-year followup or had incomplete data, leaving 70 patients
      available at a mean of 35 months. Postoperative radiographs and CT scans were
      evaluated for bone block positioning, healing, and arthritis. Any postoperative
      dislocation or any subjective complaint of occasional to frequent subluxation was
      considered a failure. Physical examination included ROM in both shoulders to
      enable comparison and instability signs (apprehension and relocation tests). Rowe
      and Walch-Duplay scores were obtained at each review. Patients were asked whether
      they were able to return to sports at the same level and practice forced overhead
      sports. Potential risk factors for nonhealing were assessed. RESULTS: At latest
      followup, 69 of 70 (98%) patients had a stable shoulder, external rotation with
      arm at the side was 9 degrees  less than the nonoperated side, and 58 (83%)
      returned to sports at preinjury level. On latest radiographs, 64 (91%) had no
      osteoarthritis, and bone block positioning was accurate, with 63 (90%) being
      below the equator and 65 (93%) flush to the glenoid surface. The coracoid graft
      healed in 51 (73%), it failed to unite in 14 (20%), and graft osteolysis was seen
      in five (7%). Bone block nonunion/migration did not compromise shoulder stability
      but was associated with persistent apprehension and less return to sports. Use of
      screws that were too short or overangulated, smoking, and age higher than 35
      years were risk factors for nonunion. CONCLUSIONS: The arthroscopic Bristow
      Latarjet procedure combined with Bankart repair for anterior instability with
      severe glenoid bone loss restored shoulder stability, maintained ROM, allowed
      return to sports at preinjury level, and had a low likelihood of arthritis.
      Adequate healing of the transferred coracoid process to the glenoid neck is an
      important factor for avoiding persistent anterior apprehension. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24942962
TI  - What are the 5-year survivorship outcomes of compressive endoprosthetic
      osseointegration fixation of the femur?
AB  - BACKGROUND: Aseptic complications such as stress shielding leading to bone loss
      are major problems associated with revision of cemented and uncemented long-stem
      tumor endoprostheses. Endoprosthetic reconstruction using compressive
      osseointegration fixation is a relatively new limb salvage technology designed to
      enhance osseointegration, prevent stress shielding, and provide fixation for
      short end-segments. QUESTIONS/PURPOSES: (1) What is the survivorship of this
      technique at minimum 5-year followup? (2) Were patient factors (age, sex, body
      mass index), oncological factors, or anatomic locations associated with implant
      failure? (3) Were there any prosthesis-related variables associated with failure?
      METHODS: A single-center, retrospective review of patients with a minimum 5-year
      followup (mean, 8 years; range, 5-12 years) treated with an osseointegration
      compressive device for endoprosthetic fixation of proximal and distal femoral
      limb salvage reconstructions was performed. We have previously published the
      implant survivorship of this patient cohort with a minimum 2-year followup and
      are now reporting on the 5-year survivorship data. From 2002 to 2008, we
      performed 22 such procedures in 22 patients. Four patients died of their disease
      within 5 years of surgery and all surviving patients (n = 18) had complete
      followup data at a minimum of 5 years. General indications for this device during
      that time were pediatric and adult patients requiring primary endoprosthetic
      reconstructions of the proximal or distal femur for benign and malignant bone
      lesions. The primary outcome was reoperations for mechanical (aseptic) failures.
      Secondary outcomes included implant removal for nonmechanical failures and any
      patient-, oncological-, or implant-related variables associated with implant
      removal. RESULTS: At a minimum of 5 years followup, overall mechanical (aseptic)
      implant survivorship was 16 of 18. Survivorship for all modes of failure
      (oncological failure, infection, arthrofibrosis, and mechanical failure) was 12
      of 18. All mechanical failures occurred early, within the first 30 months. We
      identified no patient-, oncological-, or implant-related features predictive of
      failure. CONCLUSIONS: Our intermediate-term experience with compressive
      osseointegration fixation for endoprosthetic limb reconstructions demonstrates
      with longer clinical followup, no additional mechanical failures were observed as
      compared with our early analysis. Our experience with this fixation at a minimum
      of 5-years followup adds to a very limited but increasing body of literature
      demonstrating that after a transient period of increased risk for implant
      failures, survivorship stabilizes. Assessment of this fixation strategy beyond 10
      years of clinical followup is needed. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 24942964
TI  - Editorial: basic science, applied science, and product testing.

PMID- 24942963
TI  - How has the introduction of new bearing surfaces altered the biological reactions
      to byproducts of wear and modularity?
AB  - BACKGROUND: Biological responses to wear debris were largely elucidated in
      studies focused on conventional ultrahigh-molecular-weight polyethylene (UHMWPE)
      and some investigations of polymethymethacrylate cement and orthopaedic metals.
      However, newer bearing couples, in particular metal-on-metal but also ceramic-on
      ceramic bearings, may induce different biological reactions. QUESTIONS/PURPOSES:
      Does wear debris from the newer bearing surfaces result in different biological
      responses compared with the known responses observed with conventional metal-on
      UHMWPE bearings? METHODS: A Medline search of articles published after 1996
      supplemented by a hand search of reference lists of included studies and relevant
      conference proceedings was conducted to identify the biological responses to
      orthopaedic wear debris with a focus on biological responses to wear generated
      from metal-on-highly crosslinked polyethylene, metal-on-metal, ceramic-on
      ceramic, and ceramic-on-polyethylene bearings. Articles were selected using
      criteria designed to identify reports of wear debris particles and biological
      responses contributing to prosthesis failure. Case reports and articles focused
      on either clinical outcomes or tribology were excluded. A total of 83 papers met
      the criteria and were reviewed in detail. RESULTS: Biological response to
      conventional UHMWPE is regulated by the innate immune response. It is clear that
      the physical properties of debris (size, shape, surface topography) influence
      biological responses in addition to the chemical composition of the biomaterials.
      Highly crosslinked UHMWPE particles have the potential to alter, rather than
      eliminate, the biological response to conventional UHMWPE. Metal wear debris can
      generate elevated plasma levels of cobalt and chromium ions. These entities can
      provoke responses that extend to the elicitation of an acquired immune response.
      Wear generated from ceramic devices is significantly reduced in volume and may
      provide the impression of an "inert" response, but clinically relevant biological
      reactions do occur, including granulomatous responses in periprosthetic tissues.
      CONCLUSIONS: The material composition of the device, the physical form of the
      debris, and disease pathophysiology contribute to complex interactions that
      determine the outcome to all wear debris. Metal debris does appear to increase
      the complexity of the biological response with the addition of immunological
      responses (and possibly direct cellular cytotoxicity) to the inflammatory
      reaction provoked by wear debris in some patients. However, the introduction of
      highly crosslinked polyethylene and ceramic bearing surfaces shows promising
      signs of reducing key biological mechanisms in osteolysis.

PMID- 24942965
TI  - Giants of orthopaedic surgery: Carlos E. Ottolenghi MD (1904-1984).

PMID- 24942967
TI  - Etiologic spectrum and prognosis of longitudinally extensive transverse
      myelopathies.
AB  - BACKGROUND: Patients with a first episode of longitudinal extensive transverse
      myelopathy (LETM) were reviewed with two objectives: to evaluate the clinical
      spectrum of LETM and to analyze the related clinical and laboratory variables
      that can be used as functional prognostic markers. METHODS: A retrospective
      review was conducted of clinical, radiologic and biochemical data of patients
      admitted for LETM between 1993 and 2011. RESULTS: Our cohort included 72 patients
      [median age 41 years, interquartile range (IQR) 29-61.5]. Median follow-up was 34
      months (IQR 17.2-63). The modified Rankin Scale (mRS) score was >=2 at the end of
      follow-up in 72.2%. The final diagnosis was idiopathic LETM in 22 patients,
      multiple sclerosis in 18, parainfectious disease in 11, systemic disease in 9,
      spinal cord infarction and neuromyelitis optica spectrum disorders in 3 patients
      each, and acute demyelinating encephalomyelitis, dural fistula, and tumor-related
      LETM in 2 patients each. Unfavorable outcome was associated with mRS >=2 at
      admission [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.66] and
      older age (OR 1.06, 95% CI 1.01-1.11). CONCLUSION: Idiopathic LETM was the most
      frequent diagnosis at the end of follow-up. Older age and clinically severe
      disease at onset were independent prognostic factors of poorer functional
      recovery.

PMID- 24942966
TI  - What are the patterns of prophylactic postoperative oral antibiotic use after
      foot and ankle surgery?
AB  - BACKGROUND: The CDC estimates 23% of healthcare-associated infections to be
      surgical site infections, with alarming prevalence of antibiotic-resistant
      organisms. While there is consensus regarding preoperative prophylaxis,
      orthopaedic surgeons' use of prophylactic postoperative oral antibiotics is less
      defined. QUESTIONS/PURPOSES: We investigated surgeons' use of prophylactic
      postoperative oral antibiotics after elective outpatient foot or ankle
      procedures, identifying (1) frequency of use, (2) regimen preferences, (3)
      personal indications, and (4) associated experience and demographics. METHODS:
      Using a cross-sectional survey design, a questionnaire was emailed to all active
      and candidate members of the American Orthopaedic Foot and Ankle Society.
      Supplementary questions captured demographic information. We invited 1136 members
      to participate; 22 addresses produced delivery failure messages, leaving 1114
      members as potential participants. After nonresponses and exclusions, 312 (28%)
      responses were analyzed. Statistical analysis used Pearson's chi-square test,
      Fisher's exact test, and multivariate regression. RESULTS: The majority (75%) of
      respondents reported use of prophylactic postoperative oral antibiotics. Most
      users (69%) prescribed to fewer than 25% of patients, although 16% prescribed for
      all elective cases. The most frequent regimen was cephalexin 500 mg four times a
      day (63%) and the most common duration was 5 to 7 days (50%). Surgeons' most
      common indications were previous infection (71%), medical comorbidities (65%),
      and previous wound-healing difficulties (56%). Those who do and do not prescribe
      prophylactic postoperative oral antibiotics showed no difference in surgical site
      infection rate or any demographic category. CONCLUSIONS: Surgeons' reported use
      of prophylactic postoperative oral antibiotics after elective foot or ankle
      surgery was common, without demographic association. Commonalities were
      identified in antibiotic regimen and personal indications for this practice.
      Comparative clinical studies are warranted to elucidate the efficacy of
      prophylactic postoperative oral antibiotics and establish evidence-based
      guidelines for their use.

PMID- 24942969
TI  - Family Caregivers' Knowledge of Delirium and Preferred Modalities for Receipt of
      Information.
AB  - Delirium is a life-threatening, frequently reversible condition that is often a
      sign of an underlying health problem. In-hospital mortality alone for older
      adults with delirium ranges from 25% to 33%. Early recognition of delirium is
      critical because prolonged duration poses a greater risk of poor functional
      outcomes for older adults. Family caregivers, who are familiar with the older
      adult's usual behaviors, are most likely to recognize delirium symptoms but might
      dismiss them as due to aging. It is important to learn what family caregivers
      know about delirium to ascertain their need for education. The aims of this study
      were to describe family caregivers' knowledge of delirium and preferred
      modalities for receipt of information about delirium. A cross-sectional design
      was used for this study and a survey distributed to family caregivers for older
      adults. Analysis of 134 usable surveys indicated that family caregivers need and
      want information about delirium. The preferred modalities for receipt of
      information included Internet, in-person classes, and newsletters.

PMID- 24942968
TI  - In silico design of novel broad anti-HIV-1 agents based on glycosphingolipid beta
      galactosylceramide, a high-affinity receptor for the envelope gp120 V3 loop.
AB  - Novel anti-Human immunodeficiency virus (HIV)-1 agents targeting the V3 loop of
      envelope protein gp120 were designed by computer modeling based on
      glycosphingolipid beta-galactosylceramide (beta-GalCer), which is an alternative
      receptor allowing HIV-1 entry into CD4-negative cells of neural and colonic
      origin. Models of these beta-GalCer analogs bound to the V3 loops from five
      various HIV-1 variants were generated by molecular docking and their stability
      was estimated by molecular dynamics (MDs) and binding free energy simulations.
      Specific binding to the V3 loop was accomplished primarily by non-conventional
      XH...pi interactions between CH/OH sugar groups of the glycolipids and the
      conserved V3 residues with pi-conjugated side chains. The designed compounds were
      found to block the tip and/or the base of the V3 loop, which form invariant
      structural motifs that contain residues critical for cell tropism. With the MDs
      calculations, the docked models of the complexes of the beta-GalCer analogs with
      V3 are energetically stable in all of the cases of interest and exhibit low
      values of free energy of their formation. Based on the data obtained, these
      compounds are considered as promising basic structures for the rational design of
      novel, potent, and broad-spectrum anti-HIV-1 therapeutics. 

PMID- 24942971
TI  - Subjective social status of older people across countries: the role of
      modernization and employment.
AB  - OBJECTIVES: To test and expand upon modernization theory's account of subjective
      social status (SSS) of older people in society. It was hypothesized that
      perceptions of older people's social status should be higher in more modernized
      countries and that the proportion of older people in employment should moderate
      the relationship between modernization and SSS of older people. METHODS: Data
      were from the "Experiences and Expressions of Ageism" module in the fourth round
      of the European Social Survey. The sample analyzed included 45,706 individuals
      from 25 countries in the European region. Multilevel modeling was used to test
      the hypotheses. RESULTS: The SSS of older people (aged 70 years and older) was
      perceived to be higher in countries with very high levels of modernization and in
      countries with a higher proportion of older people in employment. The positive
      association between modernization and SSS of older people was stronger within
      countries with a lower proportion of older people in employment. DISCUSSION: The
      proportion of older people who are employed is an important factor that is
      related to perceptions of the social status of older people in less modern
      societies. The individual and societal implications are discussed, specifically
      in relation to policies promoting active aging.

PMID- 24942970
TI  - The impact of activity interventions on the well-being of older adults in
      continuing care communities.
AB  - As the U.S. population ages, interventions are needed to ensure quality of life
      continues as boomers enter assisted and independent living communities (AICs).
      These transitions can significantly affect quality of life. Activity and
      continuity theories maintain that participation in discretionary/informal
      activities is crucial for psychosocial health and well-being (aspects of quality
      of life). This study evaluates the impacts of participation in discretionary
      activities on life satisfaction, social isolation, and loneliness, using data
      from a longitudinal study of older adults in AICs. Older adults who participated
      in 8 weeks of discretionary activities reported greater life satisfaction and
      lower levels of social isolation compared with non-participants. Forming
      alliances and group identities is the key for building new relationships and
      maintaining relationships in the community. Determining the impact participation
      in activities has on residents is vital to being able to help develop a more
      comprehensive understanding of how quality of life can be maintained in AICs.

PMID- 24942972
TI  - Age at immigration and the incomes of older immigrants, 1994-2010.
AB  - OBJECTIVES: Seniors comprise a growing proportion of new U.S. immigrants. We
      investigate whether late-age immigrants are disadvantaged in older age relative
      to those arriving earlier in life, based on income, reliance on public benefits,
      and access to public medical insurance. We test whether the 1996 welfare reform
      law altered the relationships between age at immigration and these outcomes.
      METHOD: Immigrants aged 65 and older in the 1994-2010 Current Population Surveys
      were classified by age at immigration. Median and logistic regressions are used
      to estimate the association between age at immigration and several outcomes and
      to test whether these associations differ for arrivals before and after welfare
      reform. RESULTS: Late-age immigration is strongly associated with lower personal
      income, lower rates of Medicare and Social Security receipt, and higher
      participation in Supplemental Security Income (SSI) and Medicaid. Arrival after
      1996 is associated with lower rates of SSI, Medicaid, and Medicare receipt. The
      association between late-age immigration and income is stronger for post-1996
      arrivals relative to earlier arrivals, whereas that between late-age immigration
      and Medicaid is weaker, suggesting that the penalty conferred by late-age
      immigration grew after reform. DISCUSSION: Late-age immigrants face formidable
      economic disadvantages exacerbated by exclusion from public benefits, with
      implications for immigration, health care, and welfare policy.

PMID- 24942973
TI  - Older Adults' Residential Proximity to Their Children: Changes After
      Cardiovascular Events.
AB  - OBJECTIVES: To assess changes in family residential proximity after a first
      cardiovascular (CV) event among older adults and to identify families most likely
      to experience such moves. METHOD: Using a nationally representative longitudinal
      study of older adults in the United States, we identified respondents with no
      prior diagnosis of CV disease (CVD). We examined subsequent development of
      stroke, heart attack, and/or heart failure among these older adults and examined
      changes in their residential proximity to their closest child before and after
      the CV event. We then compared the likelihood of changes in proximity between
      families with and without CV events. Finally, we determined which types of
      families are most likely to relocate following a CV event. RESULTS: Having a
      first CV event increases the 2-year predicted probability of children and adult
      parents moving in with and closer to each other (relative risk ratio = 1.61 and
      1.55, respectively). Families are especially likely to move after a first CV
      event if the older person experiencing the event is spouseless or has a daughter.
      DISCUSSION: CVD is a leading cause of disability, which in turn creates a
      significant need for personal care among older adults. Assessment of changes in
      family residential proximity responding to CV events is important to fully
      understand the consequences of older adults' CV events including the cost of
      caregiving.

PMID- 24942974
TI  - Bronchoalveolar lavage cellular patterns in monoclonal antibody-induced lung
      disease.
AB  - BACKGROUND: The increase in the use of monoclonal antibodies (mAB) as a targeted
      therapy for a variety of diseases has been accompanied by an increase in reports
      of interstitial lung abnormalities in treated patients. OBJECTIVE:
      Bronchoalveolar lavage (BAL) is routinely performed in these patients to rule out
      infection, so we sought to determine the BAL cellular pattern in individuals with
      mAB-induced lung disease (mAB-ILD). METHODS: We utilized a case-control study
      design. Among patients treated with mAB, cases were defined as those with
      otherwise-unexplained interstitial lung abnormalities, which resolved after
      cessation of treatment, while controls were defined as those with interstitial
      abnormalities clearly explained by other etiologies. RESULTS: From 2000 to 2012,
      we identified 9 cases and 7 controls. The mean age of the cases was 62.6 +/- 26
      years and 6 were female. The most common radiographic finding was diffuse ground
      glass opacities. The most common BAL cellular pattern was mixed inflammation with
      moderate lymphocytic and mild neutrophilic alveolitis. The cases had a higher
      mean lymphocyte count than the controls (40.1 +/- 32.6 vs. 13.1 +/- 25.5, p =
      0.008). The rest of the BAL cellular analyses were similar between the 2 groups.
      The median CD4:CD8 ratio in 7 patients with >15% lymphocytes was 0.9 (0.6-3).
      There was no significant difference in the CD4:CD8 ratio between the 2 groups.
      CONCLUSIONS: Mixed inflammation with moderate lymphocytic and mild neutrophilic
      alveolitis is the most common BAL cellular pattern in patients with mAB-ILD. Such
      findings may be useful for the early identification of mAB-ILD.

PMID- 24942976
TI  - Systemic capillary leak syndrome revealing a diffuse large B-cell lymphoma.
AB  - We report on a 75-year-old woman who presented with recurrent episodes of
      hypotension, anasarca, renal failure, hypoalbuminaemia without proteinuria,
      suggestive of systemic capillary leak syndrome (SCLS). Further investigations led
      to a diagnosis of diffuse large B-cell lymphoma. Secondary SCLS associated with
      non-Hodgkin lymphoma is reviewed. 

PMID- 24942975
TI  - Reduced crying in term infants fed high beta-palmitate formula: a double-blind
      randomized clinical trial.
AB  - BACKGROUND: Beta-palmitate (sn-2 palmitate) mimics human milk fat, enabling
      easier digestion.Therefore, we hypothesized that infants consuming high beta
      palmitate formula would have more frequent, softer stools and reduced crying
      compared to infants consuming low beta-palmitate formula. METHODS: Formula-fed
      infants were randomly assigned to receive either (1) formula with high beta
      palmitate (HBP, n = 21) or (2) regular formula with a standard vegetable oil mix
      (LBP, n = 21). A matched group of breastfed infants served as a reference (BF, n
      = 21). Crying and stool characteristics data were recorded by the parents for 3
      days before the 6- and 12-week visits. RESULTS: We found no significant
      differences in the stool frequency or consistency between the two formula groups.
      The percentage of crying infants in the LBP group was significantly higher than
      that in the HBP and BF groups during the evening at 6 weeks (88.2% vs. 56.3% and
      55.6%, p < 0.05) and during the afternoon at 12 weeks (91.7% vs. 50.0% and 40%, p
      < 0.05). The infants fed HBP had significantly shorter crying durations when
      compared with infants fed LBP formula (14.90 +/- 3.85 vs.63.96 +/- 21.76 min/day,
      respectively; p = 0.047). CONCLUSIONS: Our study indicates that consumption of a
      high beta-palmitate formula affects infant crying patterns during the first weeks
      of life. Comparable to breastfeeding, it reduced crying duration and frequency,
      primarily during the afternoon and evening hours, thereby improving the well
      being of formula-fed infants and their parents. TRIAL REGISTRATION:
      NCT00874068.Registration date March 31, 2009.

PMID- 24942977
TI  - A determination of the current causes of hyperkalaemia and whether they have
      changed over the past 25 years.
AB  - OBJECTIVE: Hyperkalaemia is a potentially lethal electrolyte disorder. The
      objective of this study was to determine if the causes of hyperkalaemia-related
      visits to the emergency department (ED) have changed since 25 years. METHODS: All
      patients presenting to the ED with hyperkalaemia between January 2009 and August
      2011 were included in this retrospective, single-centre study. Patients were
      divided into one of these three categories: mild (5.2<= K(+)<5.8 mEq/l), moderate
      (5.8<=K(+)<7.0 mEq/l) or severe hyperkalaemia (K(+)>=7.0 mEq/l). The causes of
      hyperkalaemia were divided into three groups: renal failure (RF), potassium
      increasing drugs (PIDs) or others. RESULTS: Overall, 139 patients with
      hyperkalaemia were included in the study (mean K(+) of 6.2 mEq/l): 35% with mild,
      49% with moderate and 16% with severe hyperkalaemia. Eighty-three per cent of
      patients (n = 115) had RF with creatinine levels >=1.25 mg/dl or estimated
      glomerular filtration rate (eGFR) levels <=60 ml/min/1.73 m(2). Serum potassium
      levels were significantly related with creatinine and eGFR values (P<0.001). The
      severity of hyperkalaemia was significantly related with creatinine levels >=1.25
      mg/dl (P = 0.002) and eGFR values <=60 ml/min/1.73 m(2) (P = 0.005). Seventy-five
      per cent of patients (n = 105) were taking PIDs. Potassium levels were
      significantly related with PIDs (P<0.001), in particularly spironolactone (P =
      0.001) and angiotensin-converting enzyme inhibitors (P = 0.008). The category
      'others' included 7% of patients (n = 10). CONCLUSIONS: RF (83%) and PIDs (75%)
      remain common causes of hyperkalaemia. Hyperkalaemia is significantly related
      with four variables: creatinine levels, spironolactone, ACEIs and beta-blocker
      intake. The causes of hyperkalaemia have not changed in recent years.

PMID- 24942978
TI  - Cell-based biological evaluation of a new bisamide FMS kinase inhibitor
      possessing pyrrolo[3,2-c]pyridine scaffold.
AB  - A bisamide compound 1 possessing the pyrrolo[3,2-c]pyridine nucleus was
      synthesized and biologically evaluated. It was tested for kinase inhibitory
      activity over a panel of 47 kinases, and its selectivity toward the FMS kinase
      was accidentally discovered. Compound 1 was tested over a panel of seven ovarian,
      two prostate, and six breast cancer cell lines at a single dose concentration of
      10 uM and showed high activity. It was further tested in a 5-dose mode to
      determine its IC50 and total growth inhibition (TGI) values over the 15 cell
      lines. Compound 1 showed high potency on the submicromolar scale and good
      efficacy. The cytotoxic effect of compound 1 over peritoneal macrophages was also
      investigated. Compound 1 demonstrated higher selectivity against different cancer
      cell lines compared with HS-27 fibroblasts.

PMID- 24942979
TI  - Plasticity in sunflower leaf and cell growth under high salinity.
AB  - A group of sunflower lines that exhibit a range of leaf Na(+) concentrations
      under high salinity was used to explore whether the responses to the osmotic and
      ionic components of salinity can be distinguished in leaf expansion kinetics
      analysis. It was expected that at the initial stages of the salt treatment, leaf
      expansion kinetics changes would be dominated by responses to the osmotic
      component of salinity, and that later on, ion inclusion would impose further
      kinetics changes. It was also expected that differential leaf Na(+) accumulation
      would be reflected in specific changes in cell division and expansion rates.
      Plants of four sunflower lines were gradually treated with a relatively high (130
      mm NaCl) salt treatment. Leaf expansion kinetics curves were compared in leaves
      that were formed before, during and after the initiation of the salt treatment.
      Leaf areas were smaller in salt-treated plants, but the analysis of growth curves
      did not reveal differences that could be attributed to differential Na(+)
      accumulation, since similar changes in leaf expansion kinetics were observed in
      lines with different magnitudes of salt accumulation. Nevertheless, in a high
      leaf Na(+) -including line, cell divisions were affected earlier, resulting in
      leaves with proportionally fewer cells than in a Na(+) -excluding line. A
      distinct change in leaf epidermal pavement shape caused by salinity is reported
      for the first time. Mature pavement cells in leaves of control plants exhibited
      typical lobed, jigsaw-puzzle shape, whereas in treated plants, they tended to
      retain closer-to-circular shapes and a lower number of lobes. 

PMID- 24942982
TI  - Biological applications of cryo-soft X-ray tomography.
AB  - X-rays are used for imaging many different types of biological specimen, ranging
      from live organisms to the individual cells and proteins from which they are
      made. The level of detail achieved as a result of the imaging varies depending on
      both the sample and the technique used. One of the most recent technical
      developments in X-ray imaging is that of the soft X-ray microscope, designed to
      allow the internal structure of individual biological cells to be explored. With
      a field of view of ~10-20 * ~10-20 MUm, a penetration depth of ~10 MUm and a
      resolution of ~40 nm(3), the soft X-ray microscope neatly fits between the
      imaging capabilities of light and electron microscopes.

PMID- 24942981
TI  - Nucleosome organization in the vicinity of transcription factor binding sites in
      the human genome.
AB  - BACKGROUND: The binding of transcription factors (TFs) to specific DNA sequences
      is an initial and crucial step of transcription. In eukaryotes, this process is
      highly dependent on the local chromatin state, which can be modified by
      recruiting chromatin remodelers. However, previous studies have focused mainly on
      nucleosome occupancy around the TF binding sites (TFBSs) of a few specific TFs.
      Here, we investigated the nucleosome occupancy profiles around computationally
      inferred binding sites, based on 519 TF binding motifs, in human GM12878 and K562
      cells. RESULTS: Although high nucleosome occupancy is intrinsically encoded at
      TFBSs in vitro, nucleosomes are generally depleted at TFBSs in vivo, and
      approximately a quarter of TFBSs showed well-positioned in vivo nucleosomes on
      both sides. RNA polymerase near the transcription start site (TSS) has a large
      effect on the nucleosome occupancy distribution around the binding sites located
      within one kilobase to the nearest TSS; fuzzier nucleosome positioning was thus
      observed around these sites. In addition, in contrast to yeast, repressors,
      rather than activators, were more likely to bind to nucleosomal DNA in the human
      cells, and nucleosomes around repressor sites were better positioned in vivo.
      Genes with repressor sites exhibiting well-positioned nucleosomes on both sides,
      and genes with activator sites occupied by nucleosomes had significantly lower
      expression, suggesting that actions of activators and repressors are associated
      with the nucleosome occupancy around their binding sites. It was also interesting
      to note that most of the binding sites, which were not in the DNase I
      hypersensitive regions, were cell-type specific, and higher in vivo nucleosome
      occupancy were observed at these binding sites. CONCLUSIONS: This study
      demonstrated that RNA polymerase and the functions of bound TFs affected the
      local nucleosome occupancy around TFBSs, and nucleosome occupancy patterns around
      TFBSs were associated with the expression levels of target genes.

PMID- 24942983
TI  - Eigenspace template matching for detection of lacunar infarcts on MR images.
AB  - Detection of lacunar infarcts is important because their presence indicates an
      increased risk of severe cerebral infarction. However, accurate identification is
      often hindered by the difficulty in distinguishing between lacunar infarcts and
      enlarged Virchow-Robin spaces. Therefore, we developed a computer-aided detection
      (CAD) scheme for the detection of lacunar infarcts. Although our previous CAD
      method indicated a sensitivity of 96.8% with 0.71 false positives (FPs) per
      slice, further reduction of FPs remained an issue for the clinical application.
      Thus, the purpose of this study is to improve our CAD scheme by using template
      matching in the eigenspace. Conventional template matching is useful for the
      reduction of FPs, but it has the following two pitfalls: (1) It needs to maintain
      a large number of templates to improve the detection performance, and (2)
      calculation of the cross-correlation coefficient with these templates is time
      consuming. To solve these problems, we used template matching in the lower
      dimension space made by a principal component analysis. Our database comprised
      1,143 T1- and T2-weighted images obtained from 132 patients. The proposed method
      was evaluated by using twofold cross-validation. By using this method, 34.1% of
      FPs was eliminated compared with our previous method. The final performance
      indicated that the sensitivity of the detection of lacunar infarcts was 96.8%
      with 0.47 FPs per slice. Therefore, the modified CAD scheme could improve FP rate
      without a significant reduction in the true positive rate.

PMID- 24942984
TI  - Chemical and thermal stability of N-heterocyclic ionic liquids in catalytic C-H
      activation reactions.
AB  - (1)H-NMR spectrum analyses are applied to study the chemical and thermal
      stability of selected N-heterocyclic ionic liquids within the reaction system
      that can highly efficiently activate a C-H bond of methane and convert it into
      the C-O bond in methanol. Our results indicate that under such reaction
      conditions involving using a powerful Pt-based catalyst and strong acidic
      solvent, the aromatic ring of an imidazolium cation becomes unstable generating
      an ammonium ion (NH(4)(+)). Our results also suggest that the instability of the
      imidazolium ring is more chemically (participation in reactions) than thermally
      based. Modifications of the aromatic ring structure such as pyrazolium and
      triazolium cations can increase the chemical/thermal stability of ionic liquids
      under these reaction conditions.

PMID- 24942986
TI  - Remission period in psoriasis after multiple cycles of narrowband ultraviolet B
      phototherapy.
AB  - The aim of this study was to investigate the duration of remission periods in
      psoriasis after narrowband ultraviolet B (NB-UVB) phototherapy, especially during
      multiple cycles of treatment. We analyzed 63 patients (101 cases) demonstrating
      marked improvement after NB-UVB phototherapy. The remission period was defined as
      the duration of time from the end of phototherapy until treatment using either
      phototherapy or systemic treatments was required again. It was found that an age
      of 60 years or older, history of systemic therapy within 6 months and three or
      more phototherapy cycles were significantly associated with shorter remission
      periods. Furthermore, multivariate analysis confirmed that three or more
      phototherapy cycles (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.73
      9.33; P = 0.001) and a history of systemic therapy (OR, 2.2; 95% CI, 1.27-3.95; P
      = 0.005) were independently associated with the shorter remission period. In
      conclusion, when planning NB-UVB phototherapy for psoriatic patients who have
      undergone multiple phototherapy cycles, clinicians should consider the
      possibility of shorter remission periods. 

PMID- 24942980
TI  - SL-401 and SL-501, targeted therapeutics directed at the interleukin-3 receptor,
      inhibit the growth of leukaemic cells and stem cells in advanced phase chronic
      myeloid leukaemia.
AB  - While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious
      in the treatment of chronic myeloid leukaemia (CML), some patients become
      refractory to these therapies. After confirming that interleukin-3 receptor
      (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells,
      we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion
      proteins SL-401 (DT388 -IL3) and SL-501 (DT388 -IL3[K116W]) could eradicate these
      stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the
      KBM5 cell line and its TKI-resistant KBM5-STI subline. Combinations of imatinib
      with these agents increased apoptosis in KBM5 and in primary CML cells. In six
      primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL
      401 and SL-501 decreased the absolute numbers of viable CD34(+) /CD38(-)
      /CD123(+) CML progenitor cells by inducing apoptosis. IL3-targeting agents
      reduced clonogenic growth and diminished the fraction of primitive long-term
      culture-initiating cells in samples from patients with advanced phase CML that
      were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended
      in a mouse model of primary TKI-resistant CML blast crisis. These data suggest
      that the DT-IL3 fusion proteins, SL-401 and SL-501, deplete CML stem cells and
      may increase the effectiveness of current CML treatment, which principally
      targets tumour bulk. 

PMID- 24942989
TI  - Design and synthesis of polymeric hydrogen sulfide donors.
AB  - Hydrogen sulfide (H2S) is a gaseous signaling molecule that has several important
      biological functions in the human body. Because of the difficulties of handling
      H2S gas, small organic compounds that release H2S under physiological conditions
      have been developed. The observed bioactivities of these H2S donors have
      generally been directly correlated with their H2S release properties. However,
      apart from H2S release, these H2S donors also exert biological effects by direct
      interaction with intracellular components within the cytoplasm after passive
      diffusion across cellular membranes. Here we report polymeric H2S donors based on
      ADT-OH which would alter cellular trafficking of ADT-OH to minimize the
      unfavorable interactions with intracellular components. We designed and
      synthesized a poly(ethylene glycol)-ADT (PEG-ADT) conjugate having ADT linked via
      an ether bond. Whereas ADT-OH significantly reduced cell viability in murine
      macrophages, the PEG-ADT conjugate did not show obvious cytotoxicity. The PEG-ADT
      conjugate released H2S in murine macrophages but not in the presence of serum
      proteins. The PEG-ADT conjugate was taken up by the cell through the endocytic
      pathway and stayed inside endolysosomes, which is different from the small
      amphiphilic donor ADT-OH that can directly enter the cytoplasm. Furthermore, PEG
      ADT was capable of potentiating LPS-induced inflammation. This polymeric H2S
      donor approach may help to better understand the H2S bioactivities of the H2S
      donor ADT-OH. 

PMID- 24942987
TI  - Mitochondrial DNA diversity of Anatolian indigenous domestic goats.
AB  - Anatolia has been an important region for civilizations and agricultural
      revolution as a major domestication centre for livestock species. Goats (Capra
      hircus) were among the earliest domesticated animals in this region. In this
      study, genetic diversity of Anatolian goat breeds was characterized by comparison
      of mitochondrial DNA hypervariable region 1. A total of 295 individuals,
      including 99 Anatolian Black goats, 96 Angora goats and 100 Kilis goats, were
      used. Haplogroup A was found to be the dominant haplogroup in all three breeds.
      The highest haplogroup diversity, including haplogroups A, B2, C and G, was
      observed in the Anatolian Black breed. Haplogroup D was only observed in Kilis
      and Angora goats. Haplogroup G was found in Angora and Anatolian Black breeds.
      The Anatolian goat breeds had high genetic diversity values and a weak
      phylogeographical structure. The nucleotide diversity values were found to be
      higher than those in previously studied goat breeds. The fact that Anatolia is a
      domestication centre and its geographical position as a junction of trade routes
      may have caused the higher genetic diversity of Anatolian goat breeds. 

PMID- 24942990
TI  - Anti-tumor and macrophage activation induced by alkali-extracted polysaccharide
      from Pleurotus ostreatus.
AB  - Pleurotus ostreatus is popularly consumed as traditional medicine and health food
      for enhancing immune function in China. Polysaccharides from mushroom have been
      demonstrated to possess a wide range of health beneficial properties. This study
      was carried out to elucidate the immunomodulating effects and molecular mechanism
      involved in the in vivo and in vitro anti-tumor activities of alkali-extracted
      polysaccharide (WPOP-N1) from the fruiting bodies of P. ostreatus. The results
      showed that WPOP-N1 significantly inhibited the tumor growth of Sarcoma 180 tumor
      bearing mice, and markedly increased the secretion level of TNF-alpha in serum.
      In addition, WPOP-N1 enhanced the phagocytic capability of peritoneal macrophages
      in vitro. Furthermore, the secretion of TNF-alpha and NO and the amount of TNF
      alpha and iNOS transcript were increased significantly when the peritoneal
      macrophages were exposed to WPOP-N1. Meanwhile, Western blot analysis revealed
      that the stimulation of peritoneal macrophages by WPOP-N1 induced the
      phosphorylation of p65 and a marked decrease of IkappaB expression. These results
      suggest that WPOP-N1 could activate macrophages through NF-kappaB signaling
      pathway, and the anti-tumor effects of WPOP-N1 can be achieved by its
      immunostimulating property. 

PMID- 24942991
TI  - Production of fungal chitosan from date wastes and its application as a
      biopreservative for minced meat.
AB  - Raw and processed meat contaminated with pathogenic microorganisms is a
      continuing worldwide problem facing health and industry overseers. Fungal
      chitosan was extracted, purified and characterized from Aspergillus brasiliensis
      (niger) ATCC 16404 grown in date syrup (dips) and applied as a potential meat
      biopreservative. The main features of produced chitosan were a deacetylation
      degree of 81.3%, a molecular weight of 31,000Da, 96% solubility in 1% acetic acid
      solution and a harmonized IR-spectrum to standard commercial chitosan. The
      application of fungal chitosan, as a natural and safe biopreservative for minced
      meat, was conducted in comparison with potassium sorbate, as a commercial meat
      preservative. Treated meat samples with 0.02% chitosan was the least trials in
      microbial contents, i.e. total count, coliforms, beta-glucuronidase-positive
      Escherichia coli, Enterobacteriaceae, yeasts and molds, Staphylococcus aureus and
      coagulase positive staphylococci. The antimicrobial activity of fungal chitosan
      was considerably greater than that of potassium sorbate or their combination at
      0.01% from each. Sensory characteristics, e.g. color, odor and texture, of
      treated meat with chitosan, were higher than those of control and potassium
      sorbate treated samples. Fungal chitosan, however, could be recommended as a
      powerful, natural and eco-friendly alternative for meat preservation and overall
      quality maintenance. 

PMID- 24942993
TI  - Preparation and evaluation of microspheres of xyloglucan and its thiolated
      xyloglucan derivative.
AB  - Xyloglucan is a natural polymer reported to possess mucoadhesive properties. To
      enhance the mucoadhesion potential, xyloglucan was thiolated with cysteine. The
      microspheres of xyloglucan were prepared using a biocompatible crosslinker sodium
      trimetaphosphate and it was optimized for formulation variables, namely polymer
      concentration, internal:external phase ratio and stirring speed using a Box
      Behnken experimental design. The formulation was also optimized for performance
      parameters like entrapment, t80 and % mucoadhesion. The microspheres were
      characterized by Fourier transform infrared spectroscopy, DSC and SEM for the
      optimum formula and then were reproduced by replacing the xyloglucan with
      thiomer. The microspheres formed showed entrapment efficiency of about 80%, t80
      of about 400min and % mucoadhesion of 60% while same for thiomer were 90%, 500min
      and 80% respectively. In oral glucose tolerance test protocol the thiomer
      microspheres showed significant reduction in blood glucose levels. Thus thiolated
      xyloglucan offers a better polymer for multiparticulate drug delivery. 

PMID- 24942992
TI  - Development and evaluation of paclitaxel loaded PLGA:poloxamer blend
      nanoparticles for cancer chemotherapy.
AB  - This investigation described the development of novel PLGA:poloxamer blend
      nanoparticles for intravenous administration of paclitaxel in order to limit the
      cremophor-associated adverse effects. The developed formulation was well
      characterized using various techniques including scanning electron microscopy,
      transmission electron microscopy, Fourier transform infrared spectroscopy and
      differential scanning calorimetry. The nanoparticles had an average particle size
      around 180nm and zeta potential of -22.7mV. The in vitro release study of
      nanoparticles exhibited biphasic release pattern. The non-hemolytic potential of
      the nanoparticles indicated the suitability of the developed formulation for
      intravenous administration. The PLGA:poloxamer blend nanoparticles showed
      significantly improved cytotoxicity in cell lines (MCF-7 and Colo-205), as
      compared to free drug. Further, the developed formulation was stable under the
      accelerated storage conditions. In conclusion, the results indicated that the
      developed polymeric formulation is a novel and potential alternative for the
      paclitaxel delivery. 

PMID- 24942994
TI  - Maturation of mouse bone marrow dendritic cells (BMDCs) induced by Laminaria
      japonica polysaccharides (LJP).
AB  - The seaweed Laminaria japonica has been investigated in a laboratory research for
      its medical significance and LJP has been purified now. The objective of present
      study was to look at effect of LJP on structural, phenotypic and functional
      maturation of murine BMDCs. The structural maturation of BMDCs induced by LJP was
      evaluated by transmission electron microscopy (TEM); The phenotypic maturation of
      BMDCs was studied by flow cytometry(FCM) and functional maturation of BMDCs was
      analyzed by FITC-dextran, acid phosphatase (ACP) activity and enzyme linked
      immunosorbent assay (ELISA). We hereby proved that LJP markedly induced
      maturation of BMDCs with the data of decreased the number of lysosomes,
      upregulated expression of CD80, CD83, CD86, CD40 and MHC II key membrane
      molecules on BMDCs, downregulated phagocytosis, enriched production of IL-12 and
      TNF-alpha secreted by BMDCs. Therefore it should be concluded that LJP was with
      strong ability to induce maturation of BMDCs. Our data provided direct evidence
      to suggest that LJP could be considered as an immune stimulant in improving
      immune handicapped situation and as a useful adjuvant in vaccine designing. 

PMID- 24942995
TI  - Home treatment of patients with small to medium sized acute pulmonary embolism.
AB  - Most patients with acute pulmonary embolism (PE) are still treated as inpatients.
      This is a retrospective cohort study of patients with acute PE, diagnosed using
      V/P SPECT between 2007 and 2011. Patients were treated at home if they were
      hemodynamically stable, did not require oxygen or parenteral analgetics, had no
      contraindications to anticoagulant treatment and V/P SPECT showed an extension of
      the PE of less than 40%. The aim of the study was to evaluate the efficacy and
      safety of home treatment with our algorithm. During the study period 416
      outpatients were diagnosed with acute symptomatic PE of whom in total 260 (62.5%)
      were discharged home from the emergency unit and another 47 (11%) within 24 h
      from admission. During 3 months follow-up one (0.3%) patient had a recurrent
      thrombotic event. Eleven (3.6%) patients had a major or clinically relevant bleed
      and the overall mortality was 2% (n = 6). There were no PE-related mortality.
      Home treatment should be considered and is safe in the majority of
      hemodynamically stable outpatients with small to medium size PE, quantified using
      V/P SPECT.

PMID- 24942998
TI  - Tailored eculizumab regimen for patients with atypical hemolytic uremic syndrome:
      requirement for comprehensive complement analysis.

PMID- 24942996
TI  - Exploring differences in prevalence of diagnosed, measured and undiagnosed
      hypertension: the case of Ireland and the United States of America.
AB  - OBJECTIVES: To: (1) compare prevalence of diagnosed, measured, total and
      undiagnosed hypertension among late middle-aged adults in the United States of
      America and Ireland; (2) identify the most important predictors of hypertension
      and compare them across the two countries; (3) investigate whether cross-national
      differences in prevalence rates are explained by country differences in
      behavioural risk factors. METHODS: We use data from the 2008 and 2010 waves of
      the Health and Retirement Study (n = 1,938) and the first wave (2009/2011) of The
      Irish Longitudinal Study on Ageing (n = 1,455). We employ probit models to
      determine whether individual attributes, socioeconomic characteristics and
      behavioural health factors, including smoking, alcohol consumption and obesity,
      are associated with hypertension. We do not consider whether respondents are on
      antihypertensive medication. RESULTS: Prevalence of diagnosed hypertension is
      higher in the United States of America (48.6 versus 32.4 %). Prevalence of
      undiagnosed hypertension is higher in Ireland (41.2 versus 19.7 %). Little of the
      difference in prevalence rates is explained by country differences in behavioural
      risk factors. CONCLUSIONS: A greater focus on prevention of high blood pressure
      is necessary in Ireland.

PMID- 24942997
TI  - Computed tomography-guided resection of osteoid osteoma of the sacrum: a case
      report.
AB  - INTRODUCTION: Osteoid osteoma is a benign tumor that usually occurs in the long
      bones of young adults. Its symptoms can be diverse depending on the location of
      the tumor and especially difficult to diagnose when occurring in an atypical
      location. Osteoid osteoma arising in the sacrum is extremely rare, and here, we
      present a case that was treated successfully in a minimally invasive fashion
      under computed tomography guidance. CASE PRESENTATION: A 25-year-old Asian man
      was referred to our institution due to persistent pain in the buttock after 12
      months of conservative treatment. Computed tomography and magnetic resonance
      imaging scans revealed a ring-shaped radiolucency consistent with a nidus of
      osteoid osteoma in the sacrum. The lesion was subsequently resected under
      computed tomography guidance and the histological diagnosis was compatible with
      osteoid osteoma. His postoperative course was uneventful, and at two years after
      surgery our patient is symptom-free with no evidence of recurrence. CONCLUSIONS:
      Computed tomography-guided resection of osteoid osteoma in the spinal column is
      feasible and accurate if there is adequate margin from vital organs. Although
      rare, it is important to always bear in mind the possibility of osteoid osteoma
      occurring in the sacrum when no other apparent lesion is detected.

PMID- 24942999
TI  - A comparison of the effects of nifedipine, verapamil, and low-molecular-weight
      heparin on SLIGRL-NH2-induced calcium influx through proteinase-activated
      receptor 2 activation.
AB  - BACKGROUND: Proteinase-activated receptor 2 (PAR2) may be implicated in skin
      disorders. Intracellular calcium mobilization is a key step in PAR2-induced
      signaling. AIMS: In this study, we investigated the effects of nifedipine,
      verapamil, and low-molecular-weight heparin (LMWH) on SLIGRL-NH2-induced PAR2
      mediated calcium mobilization within cells. METHODS: The intracellular calcium
      concentration was measured with fluo-8, a fluorescence indicator for free Ca(2+).
      RESULTS: Our results showed that SLIGRL-NH2 induced a dose-dependent calcium
      influx. This calcium influx was completely blocked in HaCaT cells and
      significantly blocked by LMWH in HEK293/PAR2 cells. However, both nifedipine and
      verapamil failed to inhibit the SLIGRL-NH2-induced calcium influx in either cell
      line. CONCLUSION: These results indicate that the PAR2 activation-induced calcium
      mobilization was mediated by intracellular calcium stores but not by
      extracellular calcium present in the media.

PMID- 24943001
TI  - Natural history of snoring in Hong Kong adolescents.
AB  - AIM: To determine the natural history of snoring in children when they reached
      adolescence and the underlying risk factors for persistence of habitual snoring.
      METHODS: A follow-up telephone survey was conducted to determine the natural
      history of snoring in children who reached adolescence. The targeted interviewees
      of the follow-up survey were parents of 3047 children. Adolescents who were
      snoring >=6 nights a week were defined as habitual snorers. Potential risk
      factors for persistent and incident habitual snoring were studied, including age,
      gender, allergic rhinitis, asthma, body mass index (BMI), sleep duration and
      daytime sleepiness. RESULTS: Of the 3047 subjects, 2005 (65.8%) were successfully
      interviewed by phone. The prevalence of habitual snorers was 12.7%. Ninety-one
      adolescents were persistent habitual snorers. Allergic rhinitis, male gender and
      higher BMI at follow-up were identified as significant risk factors for
      persistent habitual snoring. A further 163 children were identified as incident
      habitual snorers. The risk factors for incident habitual snoring included male
      gender, asthma, higher BMI at follow-up and younger age at the first survey. In
      the current study, the mean sleep duration was 7.6 +/- 1.0 h. Overall, 90% of the
      current cohort slept less than the lower limit of international recommendations
      for sleep duration. CONCLUSIONS: Around 40.6% of habitually snoring children
      continued to snore habitually as adolescents in the current study, while 9.2% of
      the initial non-habitual snorers became habitual snorers. Male gender and higher
      BMI were significant risk factors for both persistent and incident habitual
      snoring.

PMID- 24943000
TI  - Rationale, design, and baseline characteristics of a randomized, placebo
      controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOMETM).
AB  - BACKGROUND: Evidence concerning the importance of glucose lowering in the
      prevention of cardiovascular (CV) outcomes remains controversial. Given the multi
      faceted pathogenesis of atherosclerosis in diabetes, it is likely that any
      intervention to mitigate this risk must address CV risk factors beyond glycemia
      alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight
      and blood pressure when used as monotherapy or add-on to other antihyperglycemic
      agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG
      OUTCOMETM trial is to determine the long-term CV safety of empagliflozin, as well
      as investigating potential benefits on macro-/microvascular outcomes. METHODS:
      Patients who were drug-naive (HbA1c >=7.0% and <=9.0%), or on background glucose
      lowering therapy (HbA1c >=7.0% and <=10.0%), and were at high risk of CV events,
      were randomized (1:1:1) and treated with empagliflozin 10 mg, empagliflozin 25
      mg, or placebo (double blind, double dummy) superimposed upon the standard of
      care. The primary outcome is time to first occurrence of CV death, non-fatal
      myocardial infarction, or non-fatal stroke. CV events will be prospectively
      adjudicated by an independent Clinical Events Committee. The trial will continue
      until >=691 confirmed primary outcome events have occurred, providing a power of
      90% to yield an upper limit of the adjusted 95% CI for a hazard ratio of <1.3
      with a one-sided alpha of 0.025, assuming equal risks between placebo and
      empagliflozin (both doses pooled). Hierarchical testing for superiority will
      follow for the primary outcome and key secondary outcomes (time to first
      occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke or
      hospitalization for unstable angina pectoris) where non-inferiority is achieved.
      RESULTS: Between Sept 2010 and April 2013, 592 clinical sites randomized and
      treated 7034 patients (41% from Europe, 20% from North America, and 19% from
      Asia). At baseline, the mean age was 63 +/- 9 years, BMI 30.6 +/- 5.3 kg/m2,
      HbA1c 8.1 +/- 0.8%, and eGFR 74 +/- 21 ml/min/1.73 m2. The study is expected to
      report in 2015. DISCUSSION: EMPA-REG OUTCOMETM will determine the CV safety of
      empagliflozin in a cohort of patients with type 2 diabetes and high CV risk, with
      the potential to show cardioprotection. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01131676.

PMID- 24943002
TI  - Facile "living" radical polymerization of methyl methacrylate in the presence of
      iniferter agents: homogeneous and highly efficient catalysis from copper(II)
      acetate.
AB  - A facile homogeneous polymerization system involving the iniferter agent 1-cyano
      1-methylethyl diethyldithiocarbamate (MANDC) and copper(II) acetate (Cu(OAc)2 )
      is successfully developed in bulk using methyl methacylate (MMA) as a model
      monomer. The detailed polymerization kinetics with different molar ratios (e.g.,
      [MMA]0 /[MANDC]0 /[Cu(OAc)2 ]0 = 500/1/x (x = 0.1, 0.2, 0.5, 1.0)) demonstrate
      that this system has the typical "living"/controlled features of "living" radical
      polymerization, even with ppm level catalyst Cu(OAc)2 , first order
      polymerization kinetics, a linear increase in molecular weight with monomer
      conversion and narrow molecular weight distributions for the resultant PMMA. (1)
      H NMR spectra and chain-extension experiments further confirm the "living"
      characteristics of this process. A plausible mechanism is discussed. 

PMID- 24943003
TI  - Direct observation of lattice symmetry breaking at the hidden-order transition in
      URu2Si2.
AB  - Since the 1985 discovery of the phase transition at THO=17.5 K in the heavy
      fermion metal URu2Si2, neither symmetry change in the crystal structure nor large
      magnetic moment that can account for the entropy change has been observed, which
      makes this hidden order enigmatic. Recent high-field experiments have suggested
      electronic nematicity that breaks fourfold rotational symmetry, but direct
      evidence has been lacking for its ground state in the absence of magnetic field.
      Here we report on the observation of lattice symmetry breaking from the fourfold
      tetragonal to twofold orthorhombic structure by high-resolution synchrotron X-ray
      diffraction measurements at zero field, which pins down the space symmetry of the
      order. Small orthorhombic symmetry-breaking distortion sets in at THO with a
      jump, uncovering the weakly first-order nature of the hidden-order transition.
      This distortion is observed only in ultrapure samples, implying a highly unusual
      coupling nature between the electronic nematicity and underlying lattice. 

PMID- 24943004
TI  - Solvothermal synthesis of ternary Cu2 MoS4 nanosheets: structural
      characterization at the atomic level.
AB  - Cu2 MoS4 nanosheets are synthesized by a solvothermal method in which the Cu2 O
      starting material acts as a sacrificial template. The microstructure of the Cu2
      MoS4 nanosheets is characterized at the atomic level, and the growth mechanism is
      monitored at the nanoscale through systematic time-dependent experiments. As a
      result, the unprecedented observation of the allotropic phase change in Cu2 MoS4
      that occurs during the solvothermal process is possible. 

PMID- 24943005
TI  - Royal College of Physicians Intercollegiate Stroke Working Party evidence-based
      guidelines for the secondary prevention of stroke through nutritional or dietary
      modification.
AB  - BACKGROUND: Each year, 15 million people worldwide and 110,000 people in England
      have a stroke. Having a stroke increases the risk of having another. There are a
      number of additional known risk factors that can be modified by diet. The present
      study aimed to systematically review key nutrients and diets and their role in
      secondary prevention, as well as provide evidence-based guidelines for use in
      clinical practice. The work was conducted as part of the process to develop the
      4th edition of the Royal College of Physicians' (RCP) National Clinical Guideline
      (NCG) for Stroke. METHODS: Questions were generated by the research team, in
      consultation with the Virtual Stroke Group, an online professional interest
      group, and the RCP Intercollegiate Stroke Working Party Guideline Development
      Group. Nine questions covering several individual nutrients and diet combinations
      were defined and searches conducted up until 31 October 2011 using five
      electronic databases (Embase, Medline, Cumulative Index to Nursing and Allied
      Health Literature (CINAHL), Cochrane Library and Web of Science). All included
      studies were assessed for quality and risk of bias using van Tulder criteria for
      randomised controlled trials (RCTs) and Quality of Reporting of Meta-analyses
      (QUORUM) criteria for systematic reviews. RESULTS: Of 4287 abstracts were
      identified, 79 papers were reviewed and 29 systematic reviews and RCTs were
      included to provide evidence for the secondary prevention components of the
      guidelines. For each question, evidence statements, recommendations and practical
      considerations were developed. CONCLUSIONS: This systematic review process has
      resulted in the development of evidence-based guidelines for use in clinical
      practice and has identified areas for further research.

PMID- 24943006
TI  - Red blood cell transfusion in patients with traumatic brain injury: a systematic
      review protocol.
AB  - BACKGROUND: Anemia is a prevalent condition in critically ill patients and red
      blood cell transfusions are frequent. Although transfusions at low hemoglobin
      levels have been shown to be associated with equivalent or better outcomes than
      higher hemoglobin thresholds, clinical equipoise persists in patients with
      traumatic brain injury considering their susceptibility to secondary cerebral
      insults such as those from hypoxemia. METHODS: Our objectives are to estimate the
      frequency of red blood cell transfusion in patients with traumatic brain injury
      and to evaluate transfusion thresholds, determinants and outcomes associated with
      transfusion strategies.We will conduct a systematic review of cohort studies and
      randomized controlled trials of patients with traumatic brain injury. We will
      search MEDLINE, Embase, BIOSIS and the Cochrane Library for eligible studies. Two
      independent reviewers will screen all identified references. Studies including
      adult patients with traumatic brain injury reporting data on red blood cell
      transfusions will be eligible. We will collect data on baseline demographics,
      trauma characteristics, hemoglobin thresholds, blood transfusions and clinical
      outcomes (mortality, length of stay, complications, and so on). Two independent
      reviewers will extract data using a standardized form. We will pool cumulative
      incidences using DerSimonian and Lair random-effect models after a Freeman-Tukey
      transformation to stabilize variances. We will pool risk ratios or mean
      differences with random-effect models and Mantel-Haenszel or inverse variance
      methods in order to evaluate the association between red blood cell transfusion
      and potential determinants or outcomes. Sensitivity and subgroup analysis
      according to timing of red blood cell transfusion, traumatic brain injury
      severity, year of conduction of the study, risk of bias, notably, are planned.
      DISCUSSION: We expect to observe high heterogeneity in the proportion of
      transfused patients across studies and that the global proportion will be similar
      to the frequency observed in the general medical critically ill population. Our
      systematic review will allow us to better describe and understand current
      transfusion practices in patients with traumatic brain injury, a clinical
      population in which liberal transfusions are still advocated in the absence of
      evidence-based data. SYSTEMATIC REVIEW REGISTRATION PROSPERO: CRD42014007402.

PMID- 24943007
TI  - Quantitative assessment of the Salmonella distribution on fresh-cut leafy
      vegetables due to cross-contamination occurred in an industrial process simulated
      at laboratory scale.
AB  - Fecal pathogen distributions in fresh-cut leafy vegetables are essential to
      develop suitable sampling plans so as to detect pathogen contaminations. In this
      study, a typical fresh-cut lettuce process was reproduced at pilot scale with
      different initial inoculum levels of Salmonella on lettuce (6-7, 4 and 1 log
      CFU/g). The pathogen was determined in all processed lettuce samples (n >= 50)
      and obtained count data were used to fit different probability distributions. The
      study showed that Salmonella is homogenously distributed on fresh-cut leafy
      vegetables as a result of processing (mainly washing) at all contamination
      levels. Negative binomial and Poisson-lognormal distributions were suitable to
      describe pathogen distribution at the high and medium levels. coefficient of
      variation modified (CV) indicated no overdispersion (i.e. clustering).
      Nevertheless, further research will be needed to assess the effect of using
      disinfectants in washing water on the final distribution pattern of pathogens in
      processed fresh-cut leafy vegetables.

PMID- 24943009
TI  - [Effects of quercetin in pregnant and lactation period on weight and expression
      of insulin-like growth factors-1 mRNA of obese female rats offspring].
AB  - OBJECTIVE: To study the effect of quercetin given during pregnancy and lactation
      period of obese rats on weight and expression of insulin-like growth factors-1
      (IGF-1) mRNA of the offspring. METHODS: In the study, 8 healthy weaning female SD
      rats were randomly selected to feed the basal diet and as blank control group,
      and the others were fed with high-fat diet. When the average weight of the high
      fat diet rats was 20% as many as the average weight of the control group, we
      believed the model succeeded. Then the female SD rats were mated and the pregnant
      rats were randomly divided into 5 groups, 8 rats in each. They were fed with high
      fat diet during pregnancy and lactation, and the obese pregnant rats were
      respectively irrigated with 0 mg/kg body weight (high-fat control), 50 mg/kg body
      weight,100 mg/kg body weight, and 200 mg/kg body weight quercetin. The blank
      control group was fed with basic diet throughout the experimental period. The
      birth weight, the weights during the development of d7, d21, d56, and d98, and
      the expressions of IGF-1 mRNA in livers tissue of the F1 generation were
      measured. RESULTS: The average birth weight of the F1 generation of high fat diet
      (HFD) group was significantly higher than that of the blank control group.
      Decreased offspring birth weight was observed with the intervention of quercetin,
      which effect remained to the delectation. The quercetin also reduced the
      expression of IGF-1 mRNA in livers of the F1 generation, and this effect remained
      to the adulthood. The 200 mg/kg body weight quercetin was most significantly
      effective. CONCLUSION: The averaged birth weight of the F1 generation of obese
      pregnant rats was significantly increased, and quercetin could effectively
      inhibit the expression of IGF-1 mRNA in livers of F1 generation to decrease cell
      proliferation and cell differentiation.

PMID- 24943008
TI  - Decreased pain threshold and enhanced synaptic transmission in the anterior
      cingulate cortex of experimental hypothyroidism mice.
AB  - BACKGROUND: Thyroid hormones are essential for the maturation and functions of
      the central nervous system. Pain sensitivity is related to the thyroid status.
      However, information on how thyroid hormones affect pain processing and synaptic
      transmission in the anterior cingulate cortex (ACC) is limited. Nociceptive
      threshold and synaptic transmission in the ACC were detected in the experimental
      hypothyroidism (HT) mice. RESULTS: HT was induced by methimazole and potassium
      perchlorate in distilled drinking water for 4 weeks. The threshold of pain
      perception to hot insults, but not mechanical ones, decreased in hypothyroid
      mice. After treatment with tri-iodothyronine (T3) or thyroxine (T4) for 2 weeks,
      thermal pain threshold recovered. Electrophysiological recordings revealed
      enhanced glutamatergic synaptic transmission and reduced GABAergic synaptic
      transmission in the ACC. Supplementation with T3 or T4 significantly rescued this
      synaptic transmission imbalance. In the same model, HT caused the up-regulation
      of the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor and NR2B-containing N-methyl-D-aspartate receptors, but it down
      regulated gamma-aminobutyric acid A receptors in the ACC. Supplementation with T3
      or T4 notably recovered the levels of above proteins. CONCLUSIONS: These results
      suggest that HT promotes hypersensitivity to noxious thermal, and that
      supplementation with T3 or T4 rescues the imbalance between excitatory and
      inhibitory transmission in the ACC.

PMID- 24943011
TI  - [Current situation and comparison of age at menarche in 26 ethnic minority groups
      in Chinese girls in 2010].
AB  - OBJECTIVE: To analyze the current situation of age at menarche (AAM) in Chinese
      ethnic minority girls aged 9-18 years, and compare the AAM with that of Chinese
      Han girls from the same province or autonomous region. METHODS: Probit analyses
      were used to calculate the AAM in various ethnic minority groups of Chinese girls
      who participated in 2010 National Physical Fitness and Health Surveillance. The
      sample size of ethnic minority girls was 31 711, and the ethnic minorities were
      Mongolian, Hui, Tibetan, Uighur, Miao, Yi, Zhuang, Buyi, Korean, Dong, Yao, Bai,
      Tujia, Hani, Kazak, Dai, Li, Lisu, Wa, Shui, Dongxiang, Naxi, Kirgiz, Tu, Qiang
      and Sala. The local Han girls to compare with the AAM were also surveyed in 2010
      National Physical Fitness and Health Surveillance. RESULTS: In the 13-year-old
      group, the percentage of menarche in Sala was the lowest (32.17%), while that in
      Korean was the highest (93.23%). At the age of 18, 99.60% ethnic minority girls
      appeared menstruating. The AAM of the top 3 ethnic minority groups were Korean
      (11.79 years), Mongolian (12.44 years) and Zhuang (12.52 years); and the last 3
      ethnic minority groups were Dongxiang (14.36 years), Sala (14.32 years) and Shui
      (14.02 years). The AAM in Korean was 0.93 years earlier than that of the Han
      girls from Jilin province; the AAM in Mongolian was 0.14 years earlier than that
      of the Han girls from Neimenggu autonomous region; the AAM in Naxi and Qiang was
      close to that of the Han girls in the same province (region) (P>0.05); and the
      AAM in Hui, Uighur, Miao, Yi, Zhuang, Buyi, Dong, Yao, Bai, Tujia, Hani, Kazak,
      Dai, Li, Lisu, Wa, Shui, Dongxiang, Kirgiz, Tu, and Sala was later than that of
      the Han girls in the same province (region). The cluster analysis indicated that
      the 26 ethnic minority groups could be classified as three groups: Korean were
      classified into the earlier age group of AAM; Dongxiang, Sala, Uighur, Yi and
      Shui belonged to the later age group of AAM; and the other 20 ethnic minority
      groups were into the middle age group of AAM. CONCLUSION: There was a large
      variation among different ethnic minority groups in China. The AAM was earlier in
      Korean, and Mongolian, compared with the local Han girls, and the AAM in other
      ethnic minority groups was the same or later compared with the local Han girls.

PMID- 24943010
TI  - [Association of rs2228314 polymorphism in SREBP2 with serum lipid levels and
      obesity among children and adolescents].
AB  - OBJECTIVE: To study the relationship between rs2228314 polymorphism in sterol
      regulatory element binding protein 2 gene (SREBP2) and obesity, serum lipid
      levels in children and adolescents. METHODS: In our study, 2 030 children and
      adolescents aged from 7 to 18 years participated. Anthropometric measurements,
      including height and weight, were performed. Their serum total cholesterol (TC),
      triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density
      lipoprotein cholesterol (HDL-C) were detected. The matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to
      detect rs2228314 genotypes. RESULTS: The GC/CC genotypes of rs2228314
      polymorphisms had lower HDL-C levels than GG genotype [(0.10 +/- 0.35) mmol/L vs.
      (0.14 +/- 0.36) mmol/L, P=0.020]. The rs2228314 polymorphism was associated with
      the abnormal HDL-C level under the dominant model after adjustment for study
      samples, sex and age (OR=1.400, 95% CI: 1.027-1.907, P=0.033). The rs2228314
      polymorphism was not associated with obesity under the dominant model after
      adjustment for study samples, sex, age and HDL-C level (OR=1.178,95% CI: 0.971
      1.430, P=0.096). CONCLUSION: The GC/CC genotype carriers of SREBP2 rs2228314
      polymorphism have higher risk of abnormal HDL-C level than the individuals with
      GG genotype among children and adolescents.

PMID- 24943012
TI  - [Effect of dietary vitamin A intake on plasma vitamin A concentration in
      preschool children of Banan district, Chongqing, China].
AB  - OBJECTIVE: To study the relationship between dietary vitamin A intake and plasma
      vitamin A concentration, and establish the theoretical basis for dietary intake
      predicting vitamin A nutritional status. METHODS: By using cluster sampling, 492
      children aged 2-7 years in kindergartens in Banan district of Chongqing were
      selected. A cross-sectional nutrition and health survey was conducted, including
      the clinical examination, anthropometry, laboratory test and dietary survey.
      RESULTS: Among the children surveyed, 229 were boys, and 263 girls, the mean age
      was (4.54 +/- 0.87) years, height (107.50 +/- 7.20) cm, and weight (18.42 +/-
      3.41) kg, the mean value of plasma vitamin A was (1.04 +/- 0.30) MUmol/L. The
      prevalence of marginal vitamin A deficiency (MVAD) was 43.5%. No cases of severe
      clinical vitamin A deficiency were found (plasma vitamin A <= 0.35 MUmol/L).
      Clinical examination found no conjunctiva, corneaor skin abnormalities, and no
      Bitot's spots. Prevalence of the last two weeks colds were 27.4% (135/492), no
      diarrhea and other gastrointestinal or digestive diseases were found. The
      proportion of insufficient dietary vitamin A intake (<600 MUg RE/d) was as high
      as 50.0%. By using correlation analysis, plasma retinol concentrations were
      related to dietary vitamin A intake (r=0.162, P<0.001), and to dietary energy
      intake (r=0.107, P=0.017). After adjustment for the effects of other non-dietary
      factors on vitamin A deficiency, the multivariate logistic regression showed that
      vitamin A-rich foods of liver intake=0 g/d (OR=1.95, 95% CI: 1.05-3.61, P=0.034),
      vitamin A-rich fruits intake=0 g/d (OR=1.55, 95% CI: 1.03-2.33, P=0.034), vitamin
      A-rich vegetables intake<200 g/d (OR=3.47, 95% CI: 1.37-8.75, P=0.009) were
      important risk factors of vitamin A deficiency. But we had not found the
      correlation between the intake of meat, eggs and milk and vitamin A deficiency.
      CONCLUSION: Dietary factors may be the major risk factor of vitamin A deficiency
      in the three kindergartens. The dietary vitamin A intakes are significantly
      related to plasma retinol concentrations, and the vitamin A-rich foods intakes
      can predict the body's vitamin A nutritional status.

PMID- 24943013
TI  - [Prenatal screening for major fetal heart defects by training sonographers in
      township hospitals and county health centers: a feasibility study].
AB  - OBJECTIVE: To explore the feasibility of screening for major fetal heart disease
      by training sonographers in township or county level hospitals. METHODS: Training
      of B ultrasound scan for congenital heart defects was given to the sonographers
      from one county hospital, and thirteen township hospitals (or the district
      hospitals), and training of fetal echocardiography was given to sonographers from
      four city/county hospitals. The trained sonographers who had passed the
      examinations and had obtained qualifications after six months of independent
      practice began to screen fetal congenital heart defects. To evaluate the
      effectiveness, sensitivity and specificity of screening was calculated by using
      the diagnosis of expert neonatal/fetal echocardiographers as the gold standard.
      RESULTS: A total of 3 425 fetuses received one fetal B ultrasound screening, one
      fetal echocardiography and one neonatal echocardiography from April 1, 2004 to
      December 31, 2005. One hundred and sixty-five B ultrasound screening images
      (4.9%) from township hospitals and fifty-six fetal echocardiography images (1.7%)
      from county or city centers couldn't be reviewed because of poor quality. The
      sensitivity of fetal B ultrasound screening in the township and county hospitals
      was 30% and 0, and the specificity 93.3% and 99.9%, respectively. Nine fetuses
      with a major congenital heart disease were eventually found by the trained
      sonographers, and two cases were misdiagnosed and two unnoticed. The total
      sensitivity and specificity of fetal echocardiography were 81.8% and 99.9%,
      respectively. The sensitivity in the county and city hospitals was 66.7% and
      100%, respectively. The specificity in the county and city hospitals was 99.9%
      and 100%, respectively. CONCLUSION: Under the current circumstances, township
      hospitals are unable to perform effective fetal cardiac screening. Screening on
      fetal congenital heart disease is suggested to be taken by trained sonographers
      in county and city level medical centers.

PMID- 24943014
TI  - [Analysis for the blood mineral content of children aged 3 to 12 years in 7
      cities and 2 towns in China].
AB  - OBJECTIVE: To investigate the status of blood mineral content of children aged 3
      to 12 years in Chinese cities and countryside and explore the possible related
      influencing factors. METHODS: The multistage stratified cluster random sampling
      was used to select one kindergarten and one primary school in seven cities
      (Beijing and Guangzhou and so on) and two towns randomly. Firstly, we selected
      one bottom class, middle class, top class in one kindergarten and one second
      grade and fifth grade in one primary school randomly. Then all of the healthful
      students of these classes were investigated and the blood mineral content of
      calcium, magnesium, lead, iron, copper, and zinc were detected. RESULTS: In the
      research, 1 842 students were investigated. The means of calcium, magnesium,
      lead, iron, copper, and zinc were in the standard range. The blood lead content
      of the boys was higher than that of the girls. The blood mineral content of
      different ages had statistical significance. The blood calcium and blood copper
      contents of the preschool children were higher than those of the school children.
      However, the school children had significantly higher blood lead, iron, and zinc
      contents in comparison with those of the preschool children. The incidences of
      iron deficiency and zinc deficiency were 35.5% and 39.6%, respectively. The
      incidence of iron deficiency and zinc deficiency of different ages had
      statistical significance, and with the age increasing, the incidence showed a
      decreasing trend. The incidences of iron deficiency and zinc deficiency of
      children whose age was more than or equal to 3 years and less than 4 years were
      up to 47.1% and 64.6%, respectively. The incidence of iron deficiency of the
      children in the countryside area was significantly higher than those in the first
      tier cities. However, the incidence of zinc deficiency of the children in the
      countryside area was significantly lower than those in the first-tier cities and
      second-tier cities. CONCLUSION: The status of iron deficiency and zinc deficiency
      of children aged 3 to 12 years in Chinese cities and countryside were still
      serious. We should pay more attention to the nutrition interventional research on
      iron and zinc.

PMID- 24943015
TI  - [Assessment of accuracy of parents' perception of their 4-36 months old
      children's picky eating behavior].
AB  - OBJECTIVE: To evaluate the accuracy of parents' perception of whether their child
      is a picky eater and the specific food category the children avoideating
      according to the food frequency questionnaire. METHODS: This research selected 1
      663 infants aged 4-36 months receiving non-diary complimentary food from
      maternal, infants, nutrition and growth study (MING Study) in 8 Chinese cities in
      which a combination of systematic cluster random sampling and purposive sampling
      was used. The general information, dietary status and picky eating status were
      collected through a self-designed questionnaire from the caregiver of the
      children. According to the parents' perception, the children were classified into
      picky/non-picky groups or avoid/non-avoid to a specific food category groups.
      Mann-Whitney U test was used to compare between the groups. RESULTS: The reported
      percentage of picky eaters increased from 7.37% in 4-6 months old infants to
      36.20% in 25-36 months old infants. Most picky infants in 4-6 months and 7-12
      months old infants avoided eating dairy food (25% and 24%); while most picky
      toddlers aged 13-24 months and 25-36 months avoided eating vegetables (26.92% and
      47.46%). The infants aged 4-6 months and 7-12 months who were perceived as picky
      by their parents took more kinds of food (8 and 19.5 kinds) than those who were
      not (6 and 18 kinds), while the picky toddlers aged 13-24 months and 25-36 months
      took fewer kinds of food (28.5 and 34 kinds for picky eaters, 31 and 37 kinds for
      non-picky eaters). The parents of infants aged 4-6 months judged correctly in
      every category of food without any statistical significance; the parents of 7-12
      months old infants judged correctly only in dairy food and eggs with statistical
      significance; those of 13-24 months old infants judged correctly in every food
      category except for vegetables with statistically significant difference in the
      category of eggs; those of 25-36 months old toddlers misjudged in dairy, beans
      and grains with no statistically significant difference in every category.
      CONCLUSION: Parents tend to misjudge their children's picky eating behavior
      before the first 12 months of the child, and tend to make a more accurate
      perception after the 12th month.

PMID- 24943016
TI  - [Concentrations of fine particulate matters and ultrafine particles and
      influenced factors during winter in an area of Beijing].
AB  - OBJECTIVE: To study the concentrations of fine particulate matters and ultrafine
      particles and influenced factors during winter in an area of Beijing. METHODS:
      Real-time monitoring of particles' mass and number concentrations were conducted
      in an area of Beijing from February 7(th) to 27(th), 2013. At the same time, the
      meteorological data were also collected from the Beijing meteorological website.
      Differences of the particles' mass and number concentrations during different
      periods were analyzed using Mann-Whitney U test. Meanwhile, the influenced
      factors were also analyzed. RESULTS: The mean concentrations of fine particulate
      matters and ultrafine particles were (157.2 +/- 142.8) MUg/m3 and (25 018 +/- 9
      309) particles/cm3, respectively. The particles' number and mass concentrations
      in haze days were 1.27 times and 2.91 times higher than those in non-haze days,
      respectively. The mass concentrations of fine particulate matters in the self
      monitoring site were higher than those in the nearest central monitoring sites,
      and the hourly-average concentrations of particles were significantly consistent
      with those at the commuter times. Meanwhile, the setting off of
      fireworks/firecrackers during the Spring Festival could lead to short-term
      increases of the particles' number and mass concentrations. When the wind speed
      was low and the related humidity was high, the concentrations of particulate
      matters were relatively high, and the mass concentrations of fine particulate
      matters were lagged about 1-2 d. CONCLUSION: The level of the particulate matters
      in this area was high. Heavy traffic, setting off of fireworks/firecrackers and
      meteorological factors may be some of the main factors affecting the
      concentrations of the particulate matters in this area. Among those factors, the
      effect of setting off of fireworks/firecrackers didn't last long and the effect
      of the meteorological factors had a hysteresis effect.

PMID- 24943017
TI  - [Effects of TiO2 nanoparticles on antioxidant function and element content of
      liver and kidney tissues in young and adult rats].
AB  - OBJECTIVE: To compare the effect of TiO2 nanoparticles on antioxidant function
      and element content of liver and kidney tissues in young and adult rats. METHODS:
      Forty-eight SD male rats, half in 4-week (youth) old and half in 9-week (adult)
      old rats, were randomly divided into 8 groups, which were exposed to TiO2
      nanoparticles [(75 +/- 15) nm, anatase] through intragastric administration at 0,
      10, 50 and 200 mg/kg body weight every day for 30 days. The liver and kidney
      tissues were collected for antioxidant function and element content analysis.
      RESULTS: 200 mg/kg TiO2 nanoparticles exposure significantly increased the liver
      total superoxide dismutase (T-SOD) activity and the kidney reduced glutathione
      (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly
      decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents
      in young rats. 200 mg/kg TiO2 nanoparticles exposure significantly increased
      GSH/GSSG ratios and Rb contents and decreased Na contents in the liver of adult
      rats. No significantly difference was found in antioxidant indexes and elements
      content in the kidney of adult rats between three experimental groups and control
      group. CONCLUSION: TiO2 nanoparticles can enhance the antioxidant capacity and
      decrease the elements content in rat liver and kidney tissues. The liver is the
      more sensitive target organ and the young animals are more susceptible to TiO2
      nanoparticles toxicity by the oral routes.

PMID- 24943018
TI  - [Comparison of genetic damage in mice exposed to black carbon and ozone-oxidized
      black carbon].
AB  - OBJECTIVE: To make an assessment on the genotoxicity caused by black carbon (BC)
      and ozonized black carbon (O3-BC). METHODS: In this study, 74 healthy male ICR
      mice [weighed (28 +/- 1.5) g] were randomly divided into 7 groups, including one
      phosphate buffer solution (PBS) control group and six particles exposed groups by
      intratracheal instillation with either BC or O3-BC at the doses of 50, 100, 200
      MUg/mouse, respectively. There were 12 mice in the groups of 200 MUg/mouse and 10
      mice in others. The mice were sacrificed 24 h after four
      intratrachealinstillations. The activities of catalase (CAT) in serum and the
      levels of malondialdehyde (MDA) in lung tissue homogenate were measured. As the
      DNA damage mark, 8-hydroxyguanosine (8-OHdG) in urine and serum were quantified
      with ELISA method. Micronucleus test was used for potential genotoxicity of BC
      and O3-BC. Hematoxylin and eosin staining was used to stain lung paraffin
      section. RESULTS: The mice were in good condition during instillation, and the
      liver coefficient of the test groups was significantly lower than that of the
      control group (P<0.05). The activities of CAT in serum significantly increased in
      the 100 MUg/mouse and 200 MUg/mouse groups after being exposed to these two kinds
      of particles. The micronucleus rate in allthe BC and O3-BC exposed groups
      increased (P<0.05), but there was no statistically significant difference among
      the groups in the levels of 8-OHdG in serum and urine and MDA in lung tissue
      homogenate. Inflammatory response was found in the lung tissue under the
      microscope after exposure to BC and O3-BC. CONCLUSION: Intratracheal instillation
      of BC and O3-BC induced increasing of oxidative stress and genetic damage in
      mice. But there was no significant difference between these two particles in
      toxicity. Whether the genotoxicity of O3-BC is higher than that of BC or not is
      uncertain. Further research is needed.

PMID- 24943019
TI  - [Prognostic analysis of 525 Chinese patients with diffuse large B cell lymphoma].
AB  - OBJECTIVE: To describe the clinical characteristics, overall survival as well as
      to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma
      (DLBCL) patients. METHODS: DLBCL patients who were initially diagnosed and
      treated in Peking University Cancer Hospital from January 1995 to December 2008
      were identified and analyzed,retrospectively.The 5-year OS rates were estimated
      with Kaplan-Meier. Log-rank test was used to compare the survival curves of the
      different groups. The multivariate analysis of prognostic factors was conducted
      with Cox regression model, which included all statistically significant
      prognostic factors in the univariate analyses. RESULTS: A total of 525 DLBCL
      patients were included in this retrospective analysis, of whom, 294 were male and
      231 female (male:female=1.27:1). The median age at the initial diagnosis was 55
      (range 16-90) years, and 37.0% (n=194) were 60 years and above. Regarding the
      clinical staging at the initial diagnosis, 54 patients (10.3%) were diagnosed as
      Stage I of the disease, 152 (28.9%) as Stage II, 117 (22.3%) as Stage III and 202
      (38.5%) as Stage IV. The "B symptoms" and increased serum LDH were presented in
      206 (39.2%) and 192 (36.6%) patients, respectively. A total of 197 (37.5%)
      patients were treated with rituximab (R). The survival follow-up continued till
      31 January 2014 with a median follow-up time of 77.5 (range: 0-205) months. A
      total of 267 patients (50.9%) died during the follow-up period. The medial
      overall survival (OS) time was 84 months, and 5-year OS rate was 52.3%. There
      were six statistically significant prognostic factors that were identified in
      both univariate and multivariate analyses: gender, Ann Arbor stage, B symptom,
      serum LDH, age at initial diagnosis and rituximab treatment. The relative risk
      (RR) of these prognostic factors in the multivariate analyses were: age > 60
      years / <= 60 years=1.380 (95%CI 1.078-1.765), male / female=1.315 (95%CI 1.025
      1.687), stage III/stage I=3.034 (95%CI 1.667-5.522), stage IV/I=3.748(95%CI 2.102
      6.681), with B symptoms/without B symptoms=1.278(95%CI 0.999-1.636), serum LDH
      increased/LDH not increased=1.351(95%CI 1.057-1.726), without R treatment / with
      R treatment=1.543 (95%CI 1.182-2.015).Compared with the IPI, age >50 years/ <= 50
      years was a statistically significant factor in both univariate and multivariate
      analyses RR=1.478 (95%CI 1.148-1.902), P=0.002. CONCLUSION: Six factors were
      related to DLBCL survival: gender, Ann Arbor stage, B symptom, serum LDH, age at
      initial diagnosis and rituximab treatment. Compared with the IPI, several
      specific factors may predict a poor prognosis in Chinese DLBCL patients: male,
      age>50 years and the presence of "B symptoms". But this result is not conclusive
      until these factors are further tested.

PMID- 24943020
TI  - [A matched case-control study of risk factors in abdominal aortic aneurysm].
AB  - OBJECTIVE: To examine the potential influence factors of abdominal aortic
      aneurysm (AAA). METHODS: A 1:2 pair-matched, case-control study was conducted
      from July 2011 to December 2012. A pair was composed of one AAA patient recruited
      from the Vascular Surgery Department, Chinese PLA General Hospital and two gender
      and age-matched non-AAA subjects, one from the same hospital and the other from
      the community in Fangshan District in Beijing. Demographic data, medical history
      and the lifestyle of each subject were collected. Moreover, all the participants
      underwent abdominal ultrasound or computed tomography (CT) and peripheral venous
      blood samples were obtained. RESULTS: There were 155 case/control pairs. The
      multivariate conditional logistic regression model confirmed that suffering from
      hypertension conferred a 1.98-fold (95%CI 1.12-3.18) increased likelihood of AAA.
      Smoking was a strong independent risk factor of AAA, with odds ratios (95%
      confidence intervals) of 5.23 (2.44-11.23). Dyslipidemia (OR=2.61,95% CI 1.45
      4.70), a higher level of serum hsCRP (OR=2.43,95%CI 1.37-4.31) and homocysteine
      (OR=2.73,95% CI 1.61-4.65) were all associated with AAA. CONCLUSION: Hypertension
      and smoking are the risk factors of AAA. Dyslipidemia, hsCRP and Hcy are
      associated with AAA.

PMID- 24943022
TI  - [Establishment of early warning control charts based on the syndromic
      surveillance data of outpatient diarrhea in Beijing].
AB  - OBJECTIVE: To establish the control charts for early warning of diarrhea based on
      the syndromic surveillance data from enteric clinic in Beijing. METHODS: The
      outpatient data from enteric clinic of a Grade Three General hospital in Haidian
      district, Beijing from April 1 to Oct. 31, 2009 and from May 1 to Nov.10, 2010
      were collected, according to the moving average method, the baseline calculated,
      the value of probability alpha and MUalpha, the early warning value based on the
      formula "w=Xj+MUalphaSj" calculated and the early warning control charts drew at
      last. RESULTS: According to the harmfulness, the severity and controllability of
      diarrheal diseases, the value of probability alpha was determined as 0.01, then
      MUalpha (unilateral) as 2, based on the early warning value, the control charts
      of diarrheal diseases, bacillary dysentery and other infectious diarrhea were
      established. CONCLUSION: The enteric clinic requires to further collect baseline
      data to evaluate and continuously adjust the established control charts for the
      best early warning model in accordance with the enteric clinic.

PMID- 24943021
TI  - [Liver injury associated with treatment of multidrug-resistant tuberculosis: a
      systematic review and meta-analysis].
AB  - OBJECTIVE: To systematically evaluate the incidence of liver injury in multi-drug
      resistant tuberculosis (MDR-TB) patients with the treatment of second-line anti
      TB drugs. METHODS: Medline (January 1, 1966 to March 1, 2014), Embase (January 1,
      1974 to March 1, 2014) and the Cochrane library (January 1, 1993 to March 1,
      2014) with four Chinese databases including VIP (January 1, 1989 to March 1,
      2014), CBMDisc (January 1, 1978 to March 1, 2014), CNKI (January 1, 1994 to March
      1, 2014)and Wanfang (January 1, 1998 to March 1, 2014), were systematically
      searched with the keywords including "Tuberculosis", "multidrug-resistant", "MDR
      TB", "side effect", "adverse", "safety" and "tolerability" for the follow-up
      studies of MDR-TB patients with liver injury during the treatment of second-line
      anti-TB drugs. The relevant information was extracted and the data were analyzed
      using the random-effects model. Subgroup and sensitivity analyses were performed
      based on the diagnostic criteria, study population, study design, history of anti
      TB treatment and treatment length. RESULTS: A total of 26 articles with 3 875 MDR
      TB patients were included, of which 373 patients developed liver injury, and the
      weighed combined incidence of liver injury was 7.7%(95%CI:5.5%-10.8%). There was
      some heterogeneity among the studies. Subgroup analyses showed that the incidence
      of liver injury was higher in groups with treatment length >= 18 months and non
      Asian populations, but there was no significant difference between the groups
      (P>0.05). Among the 26 articles, only nine of them reported the diagnostic
      criteria of liver injury, while the criteria were not uniform. CONCLUSION: The
      incidence of liver injury during the treatment of second-line anti-TB drug in MDR
      TB patients was high, and the diagnostic criteria were not uniform. We should pay
      attention to the prevention and treatment of liver injury, and develop standard
      diagnostic criteria for it.

PMID- 24943023
TI  - [Relationship between brachial-ankle pulse wave velocity and metabolic syndrome].
AB  - OBJECTIVE: To evaluate the association between brachial-ankle pulse wave velocity
      (ba-PWV) and metabolic syndrome (MetS) among the Chinese elderly and the gender
      difference. METHODS: We conducted a population-based cross-sectional study in a
      representative urban area of Beijing, China. A sample of 2 102 community elderly
      (848 males, and 1 254 females) aged 60 to 95 years were included in the study.
      MetS was defined according to the 2009 harmonizing definition. RESULTS: The
      prevalence of MetS was 59.1% (50.1% in males and 65.2% in females, P<0.001). The
      baPWV value was between 8.2 to 45.6 (20.0 +/- 4.4) m/s, and showed an increasing
      trend with age (P<0.001). The partial correlation showed baPWV was positively
      associated with BMI (r=0.076, P=0.037), systolic blood pressure (r=0.380,
      P<0.001), diastolic blood pressure (r=0.276, P<0.001), triglyceride (r=0.040,
      P=0.046), fasting blood glucose (r=0.140, P<0.001), 2-hour post-meal blood
      glucose (r=0.121, P<0.001), and negatively associated with HDL-C (r=-0.128,
      P=0.048). There was a strong association between baPWV and prevalence of MetS and
      its component number in females but not in males. Compared with the lowest
      quartile of baPWV, the adjusted ORs were 1.22 (95%CI 0.83-1.79), 1.32 (95%CI 0.90
      1.93), 1.46(95%CI 1.00-2.14) in males and 1.28 (95%CI 0.93-1.77), 1.55 (95%CI
      1.12-2.16), 1.86(95%CI 1.32-2.61) in females for the second, third and top
      quartiles. CONCLUSION: The prevalence of MetS increases substantially with
      increasing levels of baPWV among the Chinese elderly, especially in females.

PMID- 24943024
TI  - [Utilization of antibacterial agents for emergency patients with acute upper
      respiratory infections in tertiary hospitals in Beijing].
AB  - OBJECTIVE: To investigate the use of antibacterial agents for emergency patients
      with acute upper respiratory infections in tertiary hospitals in Beijing.
      METHODS: We used the medical claim data for urban workers in 10 tertiary
      hospitals in Beijing from Oct. 2010 to Sep. 2012. Medical records of emergency
      patients with acute upper respiratory tract infections had been selected as the
      study sample. The proportions of antibacterial prescriptions and categories of
      antibacterial drugs were described and analyzed. RESULTS: This study included 135
      979 visitors (male: 42.7%; mean age: 43.6 +/- 16.2 years). The average
      antibacterial prescription rate was 71.2% (95%CI 71.0%-71.5%), of which the
      single kind use was 80.0% (95% CI 79.7%-80.2%). Among acute upper respiratory
      tract infections, the antibacterial prescription rate for acute tonsillitis
      visits was highest (85.1%, 95%CI 84.5%-85.6%), followed by acute laryngitis and
      bronchitis (81.69%, 95% CI 80.4%-82.8%), acute pharyngitis (81.4%, 95% CI 77.7%
      85.0%), acute sinusitis (77.0%, 95% CI 74.6%-79.4%), acute nasopharyngitis
      (74.3%, 95% CI 73.7%-75.0%), and common cold (67.6%, 95% CI 67.3%-67.9%).
      Compared with the female group, the antibacterial prescription rate for the male
      was higher (73.2%, 95%CI 72.8%-73.6% vs. 69.7%, 95%CI 69.4%-70.0%). Compared with
      the <60 years age cases, the antibacterial prescription rate for the >= 60 years
      cases was higher (72.1%, 95% CI 71.8%-72.3% vs. 66.8%, 95% CI 66.2%-67.5%). In
      the visitors who used antibacterial drugs, the average percentage of injection
      use was 50.6% (95% CI 50.3%-50.9%). The top antibacterial drugs in the list of
      varieties were the second generation cephalosporins (28.4%), followed by the
      third generation cephalosporins (21.7%), fluoroquinolones (21.0%) and macrolides
      (17.6%). CONCLUSION: The antibacterial prescription rate for acute upper
      respiratory tract infections in the general hospitals in Beijing is high, and the
      second generation cephalosporins, third generation cephalosporins,
      fluoroquinolones and macrolides take the lead in the total antibacterial drugs.

PMID- 24943025
TI  - [Analysis of tobacco use and associated factors among migrants in construction
      sites of Western China].
AB  - OBJECTIVE: To investigate the behavior of tobacco use among migrants in
      construction sites and explore the associated factors. METHODS: A total of 652
      migrants in 10 construction sites were selected in Xi'an and Tongchuan. Chi
      square and logistic regression were used to analyze the influencing factors of
      tobacco use. RESULTS: The average age of the migrants in the construction site
      was (38.23 +/- 10.61), and males occupied 82.7% (535/647) of the total. The
      current smoking rate of the migrants was 55.8% (364/652), with 64.3% (344/535) in
      males and 14.3% (16/112) in females. 82.5% (329/399) smokers wanted to quit
      smoke, however only 52.7% (210/399) had tried quitting smoking in action, and
      8.8%(35/399) quitted smoking successfully. Multivariable regression indicated
      that the migrants who were at lower age, and sick within 2 weeks, had perceived
      not difficult to stop smoking and who disagree with the benefits of smoking were
      more likely to try to quit smoking. CONCLUSION: Migrants in construction sites
      show their characteristics of old age, low level of health literacy, male
      domination, high smoking rate and high intention of quitting smoking. Tobacco
      control projects should be implemented in construction sites to promote the
      translation of smoking quitting intention into action.

PMID- 24943026
TI  - [Impact of primary care oriented outpatient benefit package design in new rural
      cooperative medical system on hypertension outpatient services utilization].
AB  - OBJECTIVE: To study the impact of primary care oriented outpatient benefits
      package design of outpatient services coverage and ladder reimbursement of
      county, town and village levels in the new rural cooperative medical system
      (NRCMs) on hypertension outpatient services utilization. METHODS: The panel data
      of treatment and control groups in 2009 and 2011 before and after the policy
      reform were drawn from the household survey data of the innovative payment system
      project. The difference in difference (DID) method was used for data analysis.
      The outcome indicators included the utilization of outpatient services of
      patients with self-reported hypertension and their main treatment locations.
      RESULTS: The primary care oriented outpatient benefit package design in the NRCMs
      reduced the probability of no treatment in the latest three months of
      hypertension by 10.2 percent points. Meanwhile, it increased the probability of
      choosing village clinic as the preferred location by 15.7 percent points.
      CONCLUSION: Primary care oriented outpatient benefits package design lead
      patients with hypertension to use the nearest outpatient services at low risk of
      disease.

PMID- 24943027
TI  - [Social determinants of the life quality among the elderly in Beijing, China].
AB  - OBJECTIVE: To verify the association between social determinants and the quality
      of life (QoL) among the elderly in Beijing. METHODS: A questionnaire household
      survey was conducted and 1 685 over 60 dwellers in Beijing were interviewed. The
      EQ-5D scale was used to measure the elderly's QoL and Time Trade-off model was
      used to calculate the EQ-5D index. Multiple linear regression and Logistic
      regression were employed to analyze the association between social determinants
      and the QoL. RESULTS: There was no statistical significant difference in the QoL
      between the urban and the rural residents (P>0.05). The elderly with higher
      education level and income or married tended to have higher overall QoL scores
      and better performance of five dimensions of the QoL (P<0.05). CONCLUSION: More
      policies should be focused on the elderly with lower social determinants in both
      urban and rural areas in Beijing.

PMID- 24943028
TI  - [Correlation between anthropometric parameters and arteriosclerosis biomarker in
      the middle-aged and the elderly].
AB  - OBJECTIVE: To investigate the correlation between anthropometric indices and
      arteriosclerosis detection indicators in the middle-aged and the elderly.
      METHODS: A cross-sectional descriptive study was made of 1 626 individuals
      (diabetics patients 23.37%, hypertensive subjects 39.48% and healthy individuals
      37.15%), aged 45 to 90 years [mean age: (61.60 +/- 10.22) years)] in Shijingshan
      District, Beijing. Their measurements: body mass index (BMI), waist circumference
      (WC), and waist to height ratio (WHtR). Arterial stiffness was assessed according
      to brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT),
      augmentation index (AI) and ankle-brachial index (ABI), which were measured by
      noninvasive detectors and equipment. The correlations between the various
      indicators were analyzed. RESULTS: The percentages of the hypertensive and
      diabetic groups of central obesity (male WC>85 cm, female WC>80 cm or WHtR>0.5)
      and of general obesity (BMI>28 kg/m2) were significantly higher than those of the
      healthy group (P<0.01). The difference between the two disease groups was not
      significant (P>0.05). There was a moderate positive correlation between the
      measures of abdominal obesity (WHtR and WC) and the general obesity indicators
      (BMI) (r=0.710 and 0.716). In the healthy group, WC and WHtR showed positive
      correlation with baPWV, IMT and ABI, and negative correlation with AI75. BMI
      showed positive correlation with IMT and negative correlation with AI75, and no
      correlation with baPWV and ABI. There was negative correlation between BMI and
      baPWV in the diabetic group. In the hypertension group, we found negative
      correlation between BMI and baPWV, maximum IMT, AI75, and also between WC and
      AI75. The simple regression straight line of baPWV versus the anthropometric
      parameters showed that the regression equations were y=0.949+1.379 x (baPWV vs.
      WHtR, R2 = 0.046, P<0.001) and y=1.133+0.006x (baPWV vs. WC, R2 = 0.027,
      P<0.001), respectively. baPWV and BMI did not have a linear relationship
      (P=0.62). CONCLUSION: WHtR and WC are superior to BMI indices in predicting
      arteriosclerosis. Anthropometric measurements for central obesity are good
      predictors of cardiovascular risk.

PMID- 24943029
TI  - [Comparison of curative effect and thrombolysis time between r-tPA application
      and urokinase in the interventional thrombectomy and thrombolysis for acute and
      severe pulmonary embolism].
AB  - OBJECTIVE: To study the influence of r-tPA and urokinase in curative effect and
      thrombolysis time on patients with acute and severe pulmonary embolism after
      interventional thrombectomy. METHODS: After reviewing and analyzing the clinical
      data of 19 acute and severe pulmonary embolism patients, we classified them into
      two groups in accordance with the application of r-tPA and urokinase to compare
      the changes of their heart rate, blood pressure, pulmonary arterial pressure,
      arterial partial pressure of oxygen and hemachrome before and after thrombolysis,
      as well as the thrombolysis effect time the two groups took. RESULTS: The heart
      rate, blood pressure, pulmonary arterial pressure, arterial partial pressure of
      oxygen of the patients in both groups gained remarkable improvement after
      operation (P<0.05); the pulmonary arterial pressure of the r-tPA patient group
      dropped but not significantly compared with that before operation (P>0.05); the
      pulmonary arterial pressure of the urokinase patient group dropped significantly
      compared with that study before operation (P<0.05); the hemachrome of both
      patient groups did not significantly drop after operation (P>0.05); the
      thrombolysis effect time by adopting r-tPA was remarkably shorter than that
      caused in thrombolysis by adopting urokinase (P<0.05). CONCLUSION: Both r-tPA and
      urokinase are effective in interventional thrombolysis for acute and severe
      pulmonary embolism. However, r-tPA could significantly shorten the time caused in
      thrombolysis without increasing any bleeding risk.

PMID- 24943030
TI  - [Decreased insulin sensitivity in rat hepatocytes with intrauterine growth
      retardation and establishment of insulin resistance cell model in vitro].
AB  - OBJECTIVE: To explore the hepatocyte insulin sensitivity of intrauterine growth
      retardation (IUGR) rats and establish an insulin resistance cell model in vitro.
      METHODS: An IUGR animal model was established by protein malnutrition during the
      mother pregnancy. On 60 d and 90 d after birth, the offspring rats were fasted
      for 12 hours and then their angular vein blood was collected to measure the
      fasting plasma glucose and fasting serum insulin level, then the insulin
      resistance index (HOMA-IR) and insulin sensitivity index (ISI) were calculated.
      The insulin sensitivity was evaluated by HOMA-IR and ISI. Primary hepatocytes
      from each group were respectively isolated by two-step perfusion with collagenase
      and were defined as normal hepatocytes group and IUGR hepatocytes group. The
      normal hepatocyte group was divided into two groups: control group and insulin
      induction group. Insulin induction group was established by primary cultures of
      normal hepatocyte incubated with varying dilutions of insulin. CCK-8 was used to
      detect the viability of the cultured hepatocytes. Glucose oxidase-peroxidase
      method kit was used to measure glucose consumption of the hepatocytes. RESULTS:
      HOMA-IR was significantly higher in IUGR rats than in the normal rats at the age
      of 60 days (t=-17.02, P<0.05) and 90 days (t=-12.52, P<0.05). ISI was
      significantly lower than in the normal rats aged 60 days (t=5.61, P<0.05) and 90
      days (t=12.42, P<0.05). There were no significant differences in hepatocyte
      viability among the control group, IUGR group and insulin induction group after
      incubation of 48 h on day 60 (F=1.34, P=0.29) and day 90 (F=0.22, P=0.81). The
      glucose consumption of the IUGR group and insulin induction group were
      significantly decreased compared with the control group on day 60 (F=9.28,
      P=0.002) and day 90 (F=56.60, P<0.001), while there was no significant difference
      between the IUGR group and insulin induction group (P=0.08, P=0.10). CONCLUSION:
      The insulin sensitivity of hepatocytes of IUGR rats decreased from adolescence to
      adulthood. High-dilution insulin may induce insulin resistance cell model in
      vitro.

PMID- 24943031
TI  - [Effect of primary site for oral and maxillary squamous cell carcinoma on
      location of neck node metastasis].
AB  - OBJECTIVE: To analyze the predilection of metastasis at levels I, II, III, IV, V
      for oral and maxillary squamous cell carcinoma on different primary sites.
      METHODS: A retrospective review was conducted of the records of 1 233 patients (1
      340 necks) from January 2000 to December 2011 with squamous cell carcinoma
      simultaneously underwent primary tumor resection and neck dissection in
      Department of Oral and Maxillary Surgery, Peking University School and Hospital
      of Stomatology. The topography of positive neck node was recorded, and the
      calculation was performed for the metastasis rate of levels I, II, III, IV, V
      based on the primary site, respectively. RESULTS: There were 557 necks with
      positive node (41.57%), and the metastasis rate for level I, II, III, IV, and V
      were 27.61%, 22.91%, 9.18%, 4.99%, 3.24%, respectively. Those in level III were
      at high risk for metastasis from carcinoma of tongue and the floor of mouth. The
      positive rate in level II was more than that in level I for tongue carcinoma, but
      for inferior gingiva carcinoma, bucca carcinoma, upper gingiva carcinoma,
      palatine carcinoma, maxillary sinuse carcinoma, intraosseous carcinoma of
      mandibular, the positive node was more likely to happen at level I compared with
      level II. CONCLUSION: Most metastases happen in levels I-III for patients with
      oral and maxillary squamous cell carcinoma, but the predilection of metastasis in
      level I, II or III is varied with the primary sites.

PMID- 24943032
TI  - [Marginal microleakage of cavities prepared with Er:YAG laser on primary teeth in
      vitro].
AB  - OBJECTIVE: To investigate the marginal microleakage after cavity preparation by
      Er:YAG laser and conventional bur applying different adhesive systems,
      conditioning surface with acid etching or not. METHODS: In the study, 50 primary
      teeth were divided into 5 groups. (1) Bur + etch-and-rinse system, (2) Bur + self
      etching system, (3) Er:YAG laser + etch-and-rinse system, (4) Er:YAG laser + self
      etching system, (5) Er:YAG laser + none-etched. The class V cavities were all
      filled with composite resin. The microleakage tests were performed, observed and
      scored under stereomicroscope. RESULTS: Bur + etch-and-rinse group had higher
      microleakage than Er:YAG laser+etch-and-rinse group, and Bur+self-etching group
      had higher microleakage than Er:YAG laser + self-etching group(P<0.05). There was
      no difference between Er:YAG laser + etch-and-rinse group and Er:YAG laser + self
      etching group, while they had significantly lower microleakage than that of
      Er:YAG + none-etched group. CONCLUSION: Composite resin restoration showed less
      marginal microleakage when all-in-one self-etch system was used after irradiation
      by Er:YAG laser on primary teeth.

PMID- 24943033
TI  - [Prevalence and significance of immunoglobulin G-anti-cyclic citrullinated
      peptide antibodies in primary Sjogren's syndrome patients].
AB  - OBJECTIVE: To investigate the prevalence and significance of IgG-anti-cyclic
      citrullinated peptides (CCP) antibody in PSS patients. METHODS: A total of 120
      patients diagnosed with PSS were investigated in the first affiliated hospital of
      Baotou Medical College from March 2006 to December 2009. IgG-anti-CCP antibody
      was assayed by enzyme-linked immunosorbent assay (ELISA), also anti-Sjogren's
      syndrome type A (SSA) and Sjogren's syndrome type B (SSB) antibody were assayed
      by immunoblotting. Erythrocyte sedimentation rate (ESR) was assayed by westergren
      in serum, and C reactive protein (CRP), IgA, IgM, IgG and IgM-RF were detected by
      immune turbidimetric. At the same time, clinical symptoms and involvement of
      important organs were observed. Following up the patients above 3 years, the
      primary Sjogren's syndrome (PSS) patients who had progressed to rheumatoid
      arthritis (RA) were evaluated. RESULTS: The positive rate of anti-CCP antibody in
      the PSS patients was 19.17%; After 3 years, more patients who were positive for
      anti-CCP antibody had progressed to RA (chi2 = 5.015,P=0.022) than the patients
      in negative group; The patients in anti-CCP antibody positive group were more
      prone to joint involvement (chi2 = 8.058,P<0.05), more swollen joints (U=152.00,
      P<0.05) and longer morning stiffness (U=100.00, P<0.05) than the patients with
      negative anti-CCP antibody, but the involvement of vital organs in the two groups
      had no significant difference (chi2 = 0.208,0.099,0.000 and 0.122, P>0.05); The
      positive rate of anti-SSA and SSB antibody in anti-CCP antibody positive group
      and negative group had no significant difference (chi2 = 0.008 and 0.56, P>0.05);
      Multiple linear regression showed that the level of anti-CCP antibody was
      positively correlated with IgM-RF levels in the PSS patients (B=0.61, 95% CI=0.36
      0.86, P<0.05), but had no significant correlation with ESR, CRP, IgA, IgM and IgG
      levels (P>0.05).There were no significant differences in the level of ESR, CRP,
      IgA, IgM and IgG between anti-CCP antibody positive group and negative group
      (P>0.05), but the level of IgM-RF in anti-CCP antibody positive group was
      significantly higher than that in the negative group (U=623.50, P<0.05).
      CONCLUSION: Positive rate of IgG-anti-CCP antibody in PSS is 19.17%, also it is
      associated with joint involvement and more prone to progressing to RA.

PMID- 24943034
TI  - [Establishment and evaluation of enzyme-linked immunosorbent assay for measuring
      human autoantibody IgG to folate receptor].
AB  - OBJECTIVE: To establish and evaluate a newly established method of enzyme-linked
      immunosorbent assay (ELISA) for measuring human autoantibody to folate receptor
      (FR). METHODS: Folate receptor was extracted and purified from healthy woman
      placenta tissues. The protein was coated on 96-well plates. Goat monoclonal
      antibody was used as detecting antibody to set up the indirect ELISA procedure.
      The sensitivity, precision and linearity of the method were evaluated. Further,
      the method was compared with the ELISA method with commercialized bovine folate
      binding protein (FBP) by determining autoantibody levels in 24 individuals.
      RESULTS: The measuring range of the standard curve was from 6.25 * 10-4 to 8 * 10
      2 (the IgG concentration of pooled plasma from healthy donors was defined as 1).
      The lowest detectable level was 3.13 * 10-4. The intra- and inter-assay
      coefficients of variations were 2.74%-8.07% and 4.16%-8.23%, respectively.
      Linearity test results were considered within acceptable limits. The data from
      FBP-ELISA and FR-ELISA were highly correlated (r=0.954, P<0.001); The value from
      FR-ELISA was higher by 14% than that from FBP-ELISA. CONCLUSION: The ELISA method
      for measuring human autoantibody IgG to folate receptor was successfully
      established using human FR as coating protein. The method is sensitive and
      repeatable and can be used in large-scale population study.

PMID- 24943035
TI  - [Experience of managing substernal goiter by totally endoscopic procedure].
AB  - To summarize the experience of managing substernal goiter by totally endoscopic
      procedure and evaluate the curative effect, we analysed eight patients diagnosed
      as substernal goiter type I and treated with totally endoscopic technique via
      central routing approach during March 2011 to June 2013 in Beijing Shijitan
      Hospital retrospectively. The feasibility, safety and curative effect of this
      surgical technique were estimated. All the cases were successfully operated with
      the totally endoscopic procedure, and the pathological result showed that 6 were
      goiter and the other 2 were minimal papillary carcinoma. None of the patients
      suffered from any complication, and the median follow up time was 6 months (1-28
      months). The totally endoscopic technique is a feasible, safe and cosmic one for
      managing substernal goiter type I. 

PMID- 24943036
TI  - Are hot charge transfer states the primary cause of efficient free-charge
      generation in polymer:fullerene organic photovoltaic devices? A kinetic Monte
      Carlo study.
AB  - Kinetic Monte Carlo simulations are used to examine the effect of high-energy,
      'hot' delocalised charge transfer (HCT) states for donor:acceptor and
      mixed:aggregate blends, the latter relating to polymer:fullerene photovoltaic
      devices. Increased fullerene aggregation is shown to enhance charge generation
      and short-circuit device current - largely due to the increased production of HCT
      states at the aggregate interface. However, the instances where HCT states are
      predicted to give internal quantum efficiencies in the region of 50% do not
      correspond to HCT delocalisation or electron mobility measured in experiments.
      These data therefore suggest that HCT states are not the primary cause of high
      quantum efficiencies in some polymer:fullerene OPVs. Instead it is argued that
      HCT states are responsible for the fast charge generation seen in spectroscopy,
      but that regional variation in energy levels are the cause of long-term,
      efficient free-charge generation. 

PMID- 24943037
TI  - Snoring amplifies the risk of heart failure and mortality in dialysis patients.
AB  - BACKGROUND: Snoring, an indicator of sleep-disordered breathing (SDB), associates
      with all-cause and cardiovascular (CV) mortality in high-risk conditions such as
      chronic heart failure (HF). Because SDB and HF are exceedingly frequent in end
      stage kidney disease (ESKD), we hypothesized that SDB as detected by snoring may
      impact upon the relationship between chronic HF and all-cause and CV mortality in
      these patients. METHODS: We tested this hypothesis in a cohort of 827 ESKD
      patients, followed up for 2.3 years. RESULTS: In this population, snoring was a
      strong modifier of the risk of chronic HF for all-cause and CV death. In fully
      adjusted Cox models, the hazard ratio (HR) associated to chronic HF for the study
      outcomes was highest in heavy snorers [all-cause death: HR 2.6 (95% CI 1.6-4.3, p
      < 0.001); CV death: HR 4.0 (95% CI 2.1-7.6, p < 0.001)], intermediate in moderate
      snorers [all-cause death: HR 1.6 (95% CI 1.1-2.2, p = 0.01); CV death: HR 1.8
      (95% CI 1.2-2.8, p = 0.01)], and lowest and not significant in non-snorers [all
      cause death: HR 0.9 (95% CI 0.6-1.6, p = NS); CV death: HR 0.8 (95% CI 0.4-1.6, p
      = NS)]. CONCLUSIONS: Snoring is a strong and independent effect modifier of the
      relationship between chronic HF and all-cause and CV mortality in ESKD. Since SDB
      and snoring are in part attributable to reversible pharyngeal oedema, intensified
      surveillance and treatment of chronic HF snorers on dialysis may translate into
      better clinical outcomes in this very high-risk population, an issue which
      remains to be tested in specifically designed clinical trials.

PMID- 24943038
TI  - Cytoplasmic localization of Lrh-1 down-regulates ovarian follicular cyp19a1a
      expression in a teleost, the orange-spotted grouper Epinephelus coioides.
AB  - Liver receptor homolog-1 (LRH-1) is a conserved member of the NR5A subfamily in
      vertebrates and a potential regulator of estrogen synthesis in the ovarian
      granulosa cells. An Lrh-1 homologue was obtained from the orange-spotted grouper
      Epinephelus coioides that contains the conserved structural features of NR5A and
      is phylogenetically closely related to NR5A2. The expression of the orange
      spotted grouper Lrh-1 is tissue-specific with relatively higher levels in the
      liver and ovary. The immunoreactive signals for Lrh-1 and Cyp19a1a were present
      in the ovarian follicular cells and germ cells. In the ovarian follicular cells,
      Lrh-1 was present both in the nucleus and cytoplasm, and colocalized with
      Cyp19a1a. The expression levels of both increased during vitellogenesis whereas
      only Cyp19a1a dramatically decreased toward maturation when Lrh-1 was localized
      almost exclusively to the cytoplasm of the follicular cells. The orange-spotted
      grouper Lrh-1 could up-regulate cyp19a1a transcription in vitro via the two
      conserved Ftz-f1 sites in cyp19a1a promoter. Chromatin immunoprecipitation
      analysis showed that the orange-spotted grouper Lrh-1 could bind cyp19a1a
      promoter in vivo with a higher abundance in the vitellogenic ovary, whereas the
      binding was dramatically decreased in the mature ovary. Taken together, the
      results of present study demonstrate that Lrh-1 plays an important role in up
      regulating cyp19a1a gene in the ovarian follicular cells during vitellogenesis,
      and the sequestration of Lrh-1 to the cytoplasm may down-regulate cyp19a1a
      expression in the mature ovary. This mechanism for modifying transcriptional
      roles of the orange-spotted grouper Lrh-1 may shed new light on the regulation of
      Cyp19a1 expression in other vertebrates as well. 

PMID- 24943039
TI  - Gonadotropin-mediated dynamic alterations during bovine oocyte maturation in
      vitro.
AB  - Gonadotropins have been widely used in human-assisted reproduction and animal
      science for the past four decades. However, the effects of gonadotropins on
      oocyte maturation at the molecular and biochemical levels are poorly understood.
      To determine the effects of gonadotropins (recombinant follicle stimulating
      hormone and urinary human menopausal gonadotropin) on oocyte maturation, we used
      the bovine oocyte in vitro maturation model. First, we studied the effects of
      increasing gonadotropin concentrations on nuclear maturation and mitochondrial
      function in oocytes. Gonadotropins at concentrations of 0.075 and 0.75 IU/ml
      improved nuclear maturation and increased inner mitochondrial membrane potential
      and ATP levels; however, there were no beneficial effects at concentrations of
      7.5 and 75 IU/ml. Second, we studied the effects of increasing gonadotropin
      concentrations on the status of methylation in matured (MII) oocytes. Aberrant
      methylation and demethylation of H19, SNRPN, and PEG3 genes were observed in MII
      oocytes at all concentrations except 0.075 IU/ml. The expression of genes that
      function in spindle formation, cell cycle control, and methylation was also
      downregulated by high gonadotropin concentrations. In conclusion, we established
      the optimal gonadotropin concentration (i.e., 0.075 IU/ml) to be used for bovine
      oocyte in vitro maturation studies. These results may provide a guide for
      clinical stimulation protocols and help to reduce the risks associated with
      gonadotropin administration during in vitro fertilization treatment. 

PMID- 24943042
TI  - Sertoli cell-based gene therapy?

PMID- 24943041
TI  - CREM variants rs4934540 and rs2295415 conferred susceptibility to nonobstructive
      azoospermia risk in the Chinese population.
AB  - To evaluate the association of variants related to spermatogenesis with
      susceptibility to Chinese idiopathic nonobstructive azoospermia (NOA), seventeen
      tag single-nucleotide polymorphisms (SNPs) in CREM, ACT, KIF17b, and SPAG8 were
      analyzed in 361 NOA patients and 368 controls by Sequenom iplex technology. The
      results showed that two CREM SNPs, rs4934540 and rs22954152, were significantly
      associated with NOA and played protective roles against the disease (P value with
      Bonferroni correction = 0.00017, odds ratio [OR] = 0.624 and P = 0.012, OR =
      0.686, respectively). Haplotype analysis of CREM gene variants suggested that
      haplotype CGTG of the SNPs, rs4934540, rs2295415, rs11592356, and rs1148247,
      exhibited significant protective effect against the occurrence of NOA (P = 0.001,
      OR = 0.659). The haplotype TATG conferred a significantly increased risk of NOA
      (P = 0.011, OR = 1.317). Furthermore, making use of quantitative RT-PCR, we
      demonstrated that relative mRNA expression of CREM in NOA patients with
      maturation arrest was only one-third of that in the controls with normal
      spermatogenesis (P < 0.0001). Our findings indicated that the polymorphisms of
      CREM gene were associated with NOA in the Chinese population and low CREM
      expression might be involved in the pathogenesis of spermatogenesis maturation
      arrest. 

PMID- 24943040
TI  - Expression and regulation of INTELECTIN1 in human granulosa-lutein cells: role in
      IGF-1-induced steroidogenesis through NAMPT.
AB  - INTELECTIN (ITLN) is an adipokine involved in the regulation of insulin
      sensitivity and inflammatory and immunity responses. Serum ITLN levels are lower
      in obese, diabetic, and polycystic ovary syndrome (PCOS) women than in control
      subjects. ITLN has never been studied in ovarian cells. Here, we identified ITLN1
      in human ovarian follicles and investigated the molecular mechanisms involved in
      the regulation of its expression in response to the insulin sensitizers metformin
      and rosiglitazone, in human granulosa-lutein cells (hGLCs) and in a human ovarian
      granulosa-like tumor cell line (KGN). We also studied the effects of human
      recombinant ITLN1 (hRom1) on steroid production and on the activation of various
      signaling pathways. Using RT-PCR, immunoblotting, and immunohistochemistry, we
      found that INTL1 is present in human follicular cells. Using ELISA, we showed
      that INTL levels are similar in plasma and follicular fluid (FF) in control
      patients, whereas they are higher in FF than in plasma in PCOS patients. In KGN
      cells and hGLCs, insulin (10(-8) M), insulin-like growth factor-1 (IGF-1; 10(-8)
      M), and metformin (10(-2) M or 10(-3) M) increased INTL1 expression (mRNA and
      protein) after 12 and 24 h of stimulation. For metformin, this effect was
      mediated by adenosine monophosphate-activated kinase (PRKA). Furthermore, hRom1
      increased nicotinamide phosphoribosyltransferase (NAMPT) expression in KGN and
      hGLCs. We also showed that hRom1 increased IGF-1-induced progesterone and
      estradiol secretion and this was associated with an increase in the STAR and
      CYP19A1 protein levels and an increase in IGF-1R signaling. Furthermore, all
      these data were abolished when NAMPT was knocked down in KGN cells, suggesting
      that INTL1 improves IGF-1-induced steroidogenesis through induction of NAMPT in
      hGLCs. 

PMID- 24943043
TI  - Adaptation to heat and exercise performance under cooler conditions: a new hot
      topic.
AB  - Chronic exposure to a stressor elicits adaptations enhancing the tolerance to
      that stressor. These adaptive responses might also improve tolerance under less
      stressful conditions. For example, historically there has been much interest in
      the adaptive responses to high-altitude, or hypoxia, and their ergogenic
      potential under sea-level, or normoxic, conditions. In contrast, the influence of
      the adaptive responses to heat on exercise under cooler conditions has received
      relatively little interest. Heat acclimation/acclimatization (HA) is known to
      increase work capacity in hot environments. Yet, aerobic exercise performance can
      progressively deteriorate as ambient temperature increases beyond ~10  degrees C,
      indicating a thermal limitation even under relatively cool conditions. The
      improved thermoregulatory capability induced by HA might attenuate this thermal
      decrement in a manner similar to that seen when exposed to hotter temperatures.
      Moreover, the suite of adaptations elicited by HA has the potential to increase
      maximal oxygen uptake, lactate threshold and economy, and thus may be ergogenic
      even under conditions where performance is not thermally limited. Indeed,
      evidence is now emerging to support an ergogenic effect of HA but the number of
      studies is limited and in some instances lack appropriate control, are confounded
      by methodological limitations, or do not address the mechanisms of action.
      Nevertheless, these tantalising insights into the ergogenic potential of heat
      will likely generate considerable interest in this new 'hot topic'. Future
      research will need to employ well-designed studies to clarify the exercise
      conditions under which ergogenic effects of HA are apparent, to elucidate the
      precise mechanisms, and to optimise HA strategies for performance. 

PMID- 24943045
TI  - Vestibular compensation in cerebellar stroke patients.
AB  - BACKGROUND AND PURPOSE: There is little evidence about the site where
      compensatory vestibular mechanisms in patients with cerebellar strokes take
      place. METHODS: To determine whether the location of a cerebellar lesion might be
      a crucial variable in vestibular compensation a sample of 22 patients with
      cerebellar stroke were tested for graviceptive function in the acute and chronic
      stage. RESULTS: Our statistical anatomical lesion analysis indicated that mainly
      lesions of the cerebellar hemispheres (lobule V, VI, VIIa) hinder vestibular
      compensation and might lead to an overcompensation. CONCLUSIONS: Overcompensation
      induced dysfunction can be explained by the absence of cerebellar inhibitory
      signals.

PMID- 24943044
TI  - Ballistic exercise as a pre-activation stimulus: a review of the literature and
      practical applications.
AB  - Post-activation potentiation (PAP) refers to the acute enhancement of muscular
      function as a direct result of its contractile history. Protocols designed to
      elicit PAP have commonly employed heavy resistance exercise (HRE) as the pre
      activation stimulus; however, a growing body of research suggests that low-load
      ballistic exercises (BE) may also provide an effective stimulus. The ability to
      elicit PAP without the need for heavy equipment would make it easier to utilise
      prior to competition. It is hypothesised that BE can induce PAP given the high
      recruitment of type II muscle fibres associated with its performance. The
      literature has reported augmentations in power performance typically ranging from
      2 to 5 %. The performance effects of BE are modulated by loading, recovery and
      physical characteristics. Jumps performed with an additional loading, such as
      depth jumps or weighted jumps, appear to be the most effective activities for
      inducing PAP. Whilst the impact of recovery duration on subsequent performance
      requires further research, durations of 1-6 min have been prescribed successfully
      in multiple instances. The effect of strength and sex on the PAP response to BE
      is not yet clear. Direct comparisons of BE and HRE, to date, suggest a tendency
      for HRE protocols to be more effective; future research should consider that
      these strategies must be optimised in different ways. The role of acute
      augmentations in lower limb stiffness is proposed as an additional mechanism that
      may further explain the PAP response following BE. In summary, BE demonstrates
      the potential to enhance performance in power tasks such as jumps and sprints.
      This review provides the reader with some practical recommendations for the
      application of BE as a pre-activation stimulus.

PMID- 24943046
TI  - A combined fermentative-chemical approach for the scalable production of pure E.
      coli monophosphoryl lipid A.
AB  - Lipid A is the lipophilic region of lipopolysaccharides and lipooligosaccharides,
      the major components of the outer leaflet of most part of Gram-negative bacteria.
      Some lipid As are very promising immunoadjuvants. They are obtained by extraction
      from bacterial cells or through total chemical synthesis. A novel, semisynthetic
      approach to lipid As is ongoing in our laboratories, relying upon the chemical
      modification of a natural lipid A scaffold for the fast obtainment of several
      other lipid As and derivatives thereof. The first requisite for this strategy is
      to have this scaffold available in large quantities through a scalable process.
      Here, we present an optimized fed-batch fermentation procedure for the gram-scale
      production of lipid A from Escherichia coli K4 and a suitable phenol-free
      protocol for its purification. A study for regioselective de-O-phosphorylation
      reaction was then performed to afford pure monophosphoryl lipid A with an
      attenuated endotoxic activity, as evaluated by cytokine production in human
      monocytic cell line THP-1 in vitro. The reported method for the large-scale
      obtainment of monophoshoryl lipid A from the fed-batch fermentation broth of a
      recombinant strain of E. coli may permit the access to novel semisynthetic lipid
      A immunoadjuvant candidates. 

PMID- 24943047
TI  - Combination of algae and yeast fermentation for an integrated process to produce
      single cell oils.
AB  - Economic and ecological reasons cause the industry to develop new innovative bio
      based processes for the production of oil as renewable feedstock. Petroleum
      resources are expected to be depleted in the near future. Plant oils as sole
      substituent are highly criticized because of the competitive utilization of the
      agricultural area for food and energy feedstock production. Microbial lipids of
      oleaginous microorganisms are therefore a suitable alternative. To decrease
      production costs of microbial lipids and gain spatial independence from
      industrial sites of CO2 emission, a combination of heterotrophic and phototrophic
      cultivation with integrated CO2 recycling was investigated in this study. A
      feasibility study on a semi-pilot scale was conducted and showed that the
      cultivation of the oleaginous yeast Cryptococcus curvatus on a 1.2-L scale was
      sufficient to supply a culture of the oleaginous microalgae Phaeodactylum
      tricornutum in a 21-L bubble column reactor with CO2 while single cell oils were
      produced in both processes due to a nutrient limitation. 

PMID- 24943048
TI  - A novel two-stage surgical approach to treat chronic lymphedema.
AB  - Surgical treatment of chronic lymphedema has seen significant advances. Suction
      assisted protein lipectomy (SAPL) has been shown to safely and effectively reduce
      the solid component of swelling in chronic lymphedema. However, these patients
      must continuously use compression garments to control and prevent recurrence.
      Microsurgery procedures, including lymphaticovenous anastomosis (LVA) and
      vascularized lymph node transfer (VLNT), have been shown to be effective in the
      management of the fluid component of lymphedema and allow for decreased garment
      use. SAPL and VLNT were applied together in a two-stage approach in two patients
      with chronic lymphedema after treatment for breast cancer. SAPL was used first to
      remove the chronic, solid component of the soft-tissue excess. Volume excess in
      our patients' arms was reduced an average of approximately 83% and 110% after
      SAPL surgery. After the arms had sufficiently healed and the volume reductions
      had stabilized, VLNT was performed to reduce the need for continuous compression
      and reduce fluid re-accumulation. Following the VLNT procedures, the patients
      were able to remove their compression garments consistently during the day and
      still maintain their volume reductions. Neither patient had any postoperative
      episodes of cellulitis. SAPL and VLNT can be combined to achieve optimal outcomes
      in patients with chronic lymphedema. 

PMID- 24943051
TI  - Laparoscopic appendicectomy: an operation for all trainees but does the learning
      curve continue into consultanthood?
AB  - BACKGROUND: In public hospitals, the work-up and surgery for patients with
      appendicitis is predominantly performed by surgical registrars, whereas in
      private hospitals, it is performed by consultants. This study aims to demonstrate
      the difference, if any, in the demographics, work-up, management and complication
      rate of patients in these two groups. METHODS: This was a retrospective review of
      all patients who underwent laparoscopic appendicectomy at a major public hospital
      and major private hospital over the same 13 months. Data included demographics,
      admission details, work-up, length of stay, time to surgery, histology and
      complications. Fisher's exact test and the unpaired t-test were performed to look
      at the statistical difference between these two groups. RESULTS: Total
      laparoscopic appendicectomies were 164 (public) and 105 (private). Median waiting
      times to operation were 13 and 9.5 h, respectively. Histological findings of
      appendicitis/neoplasia/normal appendix were 83.5/3.0/13.4% and 81.9/1.9/16.2%.
      Histological findings of gangrene or perforation were 26.2% and 11.6% (P =
      0.0081). The proportion of those who had surgery more than 24 h after admission
      was 12.2% and 4.8% (P = 0.0517). Rates of pelvic collection were 1.2% and 1.9% (P
      = 0.6448), wound infection rates were 2.4% and 1.9% (P = 1) and overall
      complication rates were 7.3% and 8.6% (P = 0.8165). Mean operative time was 49.79
      min for consultants and 67.98 min for registrars (P < 0.0001). CONCLUSION:
      Consultants are faster at laparoscopic appendicectomies than registrars. A
      consultant lead service in a private hospital has earlier operation times and
      less patients ending up with gangrenous or perforated appendicitis but does not
      alter complication rates.

PMID- 24943052
TI  - Weather and headache onset: a large-scale study of headache medicine purchases.
AB  - It is widely recognized that weather changes can trigger headache onset. Most
      people who develop headaches choose to self-medicate rather than visit a hospital
      or clinic. We investigated the association between weather and headache onset
      using large-sample sales of the headache medicine, loxoprofen. We collected daily
      sales figures of loxoprofen and over-the-counter drugs over a 1-year period from
      a drugstore chain in western Shizuoka prefecture, Japan. To adjust for changes in
      daily sales of loxoprofen due to social environmental factors, we calculated a
      proportion of loxoprofen daily sales to over-the-counter drug daily sales. At the
      same time, we obtained weather data for the study region from the website of the
      Japan Meteorological Agency. We performed linear regression analysis to ascertain
      the association between weather conditions and the loxoprofen daily sales
      proportion. We also conducted a separate questionnaire survey at the same
      drugstores to determine the reason why people purchased loxoprofen. Over the
      study period, we surveyed the sale of hundreds of thousands of loxoprofen
      tablets. Most people purchased loxoprofen because they had a headache. We found
      that the sales proportion of loxoprofen increased when average barometric
      pressure decreased, and that precipitation, average humidity, and minimum
      humidity increased on loxoprofen purchase days compared to the previous day of
      purchases. This study, performed using a large dataset that was easy-to-collect
      and representative of the general population, revealed that sales of loxoprofen,
      which can represent the onset and aggravation of headache, significantly
      increased with worsening weather conditions. 

PMID- 24943054
TI  - Divergent synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl
      1H-pyrroles from 2,4-pentadienenitriles and isocyanides.
AB  - An efficient and divergent one-pot synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl
      1H-pyrroles and 3-alkenyl-1H-pyrroles from readily accessible 2,4
      pentadienenitriles with isocyanide based on reaction condition selection has been
      described. The reaction of 2,4-pentadienenitriles with ethyl isocyanoacetate
      undergoes a formal [2 + 3] annulation either to generate 2,3-dihydro-1H-pyrroles
      in the presence of DBU (0.3 equiv.) in EtOH at room temperature or to give 3
      alkyl-1H-pyrroles in the presence of DBU (2.0 equiv.) in EtOH under reflux.
      Moreover, the 2,3-dihydro-1H-pyrroles could be converted to 3-alkenyl-1H-pyrroles
      with DDQ as an oxidant. 

PMID- 24943053
TI  - Structural and functional correlates of epileptogenesis - does gender matter?
AB  - In the majority of neuropsychiatric conditions, marked gender-based differences
      have been found in the epidemiology, clinical manifestations, and therapy of
      disease. One possible reason is that sex differences in cerebral morphology,
      structural and functional connections, render men and women differentially
      vulnerable to various disease processes. The present review addresses this issue
      with respect to the functional and structural correlates to some forms of
      epilepsy. 

PMID- 24943055
TI  - Interaction of adrenocortical activity and autonomic arousal on children's
      externalizing and internalizing behavior problems.
AB  - The psychobiology of stress involves two major components, the hypothalamic
      pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS). Research has
      revealed the association between behavior problems and the psychobiology of
      stress, yet findings are inconsistent and few studies have addressed the moderate
      correlations between behavior problems. This study examines the individual and
      interactive effects of HPA and ANS on child behavior problems while taking into
      account the comorbidity of externalizing and internalizing problems. Four saliva
      samples were collected from each participant in a community sample (N = 429; aged
      11-12 years; 50.49 % male), which were assayed for cortisol (HPA) and alpha
      amylase, sAA (ANS). Children's behavior problems were assessed using parent
      report and self-report versions of the Child Behavior Checklist. Latent variables
      were constructed to represent trait-like individual differences in cortisol and
      sAA. Low levels of HPA axis activity were associated with higher levels of both
      externalizing and internalizing problems, but only among children with low ANS
      arousal. The association between externalizing and internalizing problems
      diminished to non-significant after taking into account the influence of HPA axis
      activity and ANS arousal, which suggests that the psychobiology of stress
      explains a fair proportion of comorbidity of behavior problems. The findings
      support that interaction between HPA axis and ANS functioning has potential to
      clarify prior mixed findings and advance our understanding of the child behavior
      problems. 

PMID- 24943057
TI  - High sitting time or obesity: Which came first? Bidirectional association in a
      longitudinal study of 31,787 Australian adults.
AB  - OBJECTIVE: Evidence on the direction of the association between sitting time and
      obesity is limited. The prospective associations between baseline total sitting
      time and subsequent changes in body mass index (BMI), and baseline BMI and
      subsequent changes in sitting time were examined. METHODS: BMI, from self
      reported height and weight, and a single-item measure of sitting time were
      ascertained at two time points (3.4 +/- 0.96 years apart) in a prospective
      questionnaire-based cohort of 31,787 Australians aged 45-65 years without severe
      physical limitations. RESULTS: In a fully adjusted model, baseline obesity was
      associated with increased sitting time among all participants (adjusted odds
      ratio [aOR] = 1.20 [95% CI, 1.11-1.30]; P < 0.001) and in most subgroups. The
      association was significant among those who were sitting <4 hours/day (aOR = 1.24
      [95% CI, 1.07-1.44]; P = 0.004) and 4-8 hours/day at baseline (aOR=1.18 [95% CI,
      1.06-1.32]; P = 0.003), but not in the high sitting groups (P = 0.111 and 0.188
      for 8-11 and >=11 sitting hours/day, respectively). Nonsignificant and
      inconsistent results were observed for the association between baseline sitting
      time and subsequent change in BMI. CONCLUSIONS: Our findings support the
      hypothesis that obesity may lead to a subsequent increase in total sitting time,
      but the association in the other direction is unclear.

PMID- 24943056
TI  - Attention-deficit/hyperactivity disorder symptoms mediate the association between
      deficits in executive functioning and social impairment in children.
AB  - We investigated whether symptoms of attention-deficit/hyperactivity disorder
      (ADHD) are pathways through which deficits in inhibition and working memory are
      associated with teacher- and parent-rated social impairment in children.
      Participants were 64 children (55% males; 53% with ADHD) in grades 3-6.
      Consistent with our hypotheses, the association between inhibition and social
      impairment was mediated by hyperactivity/impulsivity and the association between
      working memory and social impairment was mediated by inattention. Support was not
      obtained for alternative models wherein the association between inhibition and
      social impairment was mediated by inattention, and the association between
      working memory and social impairment was mediated by hyperactivity/impulsivity.
      Further, tests of hierarchical models suggest that neither inhibition nor working
      memory is primary but, rather, that these cognitive processes are related to one
      another and that they collectively (but not uniquely) contribute to
      hyperactivity/impulsivity and inattention. These findings have implications for
      conceptual models of ADHD, for understanding factors that influence and sustain
      social impairment among youth with symptoms of the disorder, and for
      interventions aimed to addressing such impairment.

PMID- 24943058
TI  - Dimensional assessment of anxiety disorders in parents and children for DSM-5.
AB  - The current shift in the DSM towards the inclusion of a dimensional component
      allows clinicians and researchers to demonstrate not only the presence or absence
      of psychopathology in an individual, but also the degree to which the disorder
      and its symptoms are manifested. This study evaluated the psychometric properties
      and utility of a set of brief dimensional scales that assess DSM-based core
      features of anxiety disorders, for children and their parents. The dimensional
      scales and the Screen for Child Anxiety Related Emotional Disorders (SCARED-71),
      a questionnaire to assess symptoms of all anxiety disorders, were administered to
      a community sample of children (n = 382), aged 8-13 years, and their mothers (n =
      285) and fathers (n = 255). The dimensional scales assess six anxiety disorders:
      specific phobia, agoraphobia, panic disorder, social anxiety disorder,
      generalized anxiety disorder, and separation anxiety disorder. Children rated
      their own anxiety and parents their child's anxiety. The dimensional scales
      demonstrated high internal consistency (alpha > 0.78, except for father reported
      child panic disorder, for reason of lack of variation), and moderate to high
      levels of convergent validity (rs  = 0.29-0.73). Children who exceeded the SCARED
      cutoffs scored higher on the dimensional scales than those who did not, providing
      preliminary support for the clinical sensitivity of the scales. Given their
      strong psychometric properties and utility for both child and parent report,
      addition of the dimensional scales to the DSM-5 might be an effective way to
      incorporate dimensional measurement into the categorical DSM-5 assessment of
      anxiety disorders in children.

PMID- 24943059
TI  - Response to the letter: Pregnancy outcomes in older women.

PMID- 24943060
TI  - Calcitonin gene- and parathyroid hormone-related peptides in normotensive and
      preeclamptic pregnancies: a nested case-control study.
AB  - PURPOSE: To identify whether CGRP and PTHrP serve as screening biomarkers for
      early detection of preeclampsia or even before the development of preeclampsia in
      early pregnancy. METHODS: It was a nested case-control study. The subjects were
      divided into normotensive (controls) and preeclamptic (cases) groups. Serum
      samples of 132 cases and 132 controls were collected during pregnancy at three
      different gestational periods and one sample post delivery, from within the
      cohort of pregnant women reporting to antenatal clinic. Circulating levels of
      CGRP and PTHrP were analyzed by enzyme-linked immunosorbent assay. RESULTS:
      Maternal serum concentrations of CGRP and PTHrP increased with the advancement of
      gestation age in both normotensive and preeclamptic pregnancies but the
      significantly less increased levels were observed in preeclamptic pregnancies as
      compared with normotensive pregnancies. In postpartum period level of CGRP
      significantly falls in both groups although level of PTHrP continues to increase
      even after delivery. Maternal serum CGRP and PTHrP concentrations were positively
      correlated with the infant's birth weights. CONCLUSION: Maternal circulating CGRP
      and PTHrP concentrations were significantly lower in women with preeclampsia,
      which may contribute to the development of preeclampsia.

PMID- 24943061
TI  - Association of the progesterone receptor gene polymorphism (PROGINS) with
      endometriosis: a meta-analysis.
AB  - BACKGROUND: Reported associations of progesterone receptor gene polymorphism
      (PROGINS) with endometriosis have been inconsistent. AIM OF THE STUDY: To
      evaluate the association between the PROGINS polymorphism and the risk of
      endometriosis. METHODOLOGY: A meta-analysis of 12 published case-control studies
      with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We
      estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis
      association with the PROGINS polymorphism. RESULTS: An association between the
      presence of the variant allele and risk of endometriosis was found, more in the
      homozygous and recessive models (OR 1.41-1.43, p = 0.15-0.17), and less in the
      dominant and co-dominant models (OR 1.22, p = 0.11-0.15). Reanalysis without the
      studies whose controls deviated from the Hardy-Weinberg Equilibrium did not
      materially alter the dominant and co-dominant effects (OR 1.19-1.22, p = 0.19
      0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09).
      The subgroups based on geography showed increased risk associations, consistently
      significant in the European (OR 1.52-2.72, p = 0.0008-0.03) but not in the
      Brazilian studies, where ORs ranged from reduced (OR 0.70-0.74, p = 0.54-0.61) to
      increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all
      comparisons to the dominant and co-dominant models (I (2) = 38-70 %), except in
      the European subgroup, which had zero heterogeneity (I (2) = 0 %) in all genetic
      models, as did all homozygous and recessive effects. CONCLUSION: This meta
      analysis provides a comprehensive profile of the role of the PROGINS polymorphism
      in endometriosis by exploring the magnitude of the summary effects with modifier
      analysis. This magnitude is expressed with modulation or exacerbation of the
      summary effects, as defined by the parameters of the analysis. Thus, the results
      showed trend towards an increased risk of the variant PROGINS allele and
      susceptibility for the endometriosis.

PMID- 24943062
TI  - Pharmacological interactions between rifampicin and antiretroviral drugs:
      challenges and research priorities for resource-limited settings.
AB  - Coadministration of antituberculosis and antiretroviral therapy is often
      inevitable in high-burden countries where tuberculosis (TB) is the most common
      opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin
      and many antiretroviral drugs is complicated by pharmacokinetic drug-drug
      interactions. Rifampicin is a very potent enzyme inducer, which can result in
      subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and
      antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in
      overlapping adverse effect profiles. This review provides an overview of the
      pharmacological interactions between rifampicin-based TB treatment and
      antiretroviral drugs in adults living in resource-limited settings. Major
      progress has been made to evaluate the interactions between TB drugs and
      antiretroviral therapy; however, burning questions remain concerning nevirapine
      and efavirenz effectiveness during rifampicin-based TB treatment, treatment
      options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase
      inhibitor resistance or intolerance, and exact treatment or dosing schedules for
      vulnerable patients including children and pregnant women. The current research
      priorities can be addressed by maximizing the use of already existing data,
      creating new data by conducting clinical trials and prospective observational
      studies and to engage a lobby to make currently unavailable drugs available to
      those most in need.

PMID- 24943063
TI  - Gentamicin and renal function: lessons from 15 years' experience of a
      pharmacokinetic service for extended interval dosing of gentamicin.
AB  - BACKGROUND: Extended interval dosing (EID) of gentamicin most commonly involves
      dosing every 24 hours, but patients with impaired renal function may require a
      longer dose interval. This study examines a large database of patients treated
      with gentamicin from 1996 to 2010 to see how many patients with renal impairment
      would have benefited from dose intervals >24 hours and to define the incidence of
      nephrotoxicity. METHODS: All patients aged >= 16 years who had received
      gentamicin by EID over the 14-year period and had concentration data available
      were examined. End points included the numbers (%) achieving the target peak
      concentration [predicted maximum gentamicin concentration (C(max))] >10 mg/L, the
      target trough concentration at 24 hours [predicted minimum gentamicin
      concentration (C(min24)] <0.5 mg/L, and the target area under the curve over 24
      hours of 70-100 mg/L . h. How these related to various creatinine clearance
      (CL(cr)) groupings was also examined, as was the number who developed
      nephrotoxicity (increase in creatinine of >= 0.04 mmol/L). RESULTS: After
      exclusions, information was available on 4523 patients. Of these, 96% achieved
      the target C(max), 83% the target C(min24), and 54% the target area under the
      curve over 24 hours. Of the 73% of patients with CL(cr) >= 60 mL/min, 98% and 97%
      achieved the target Cmax and C(min24), respectively. Of the 19% of patients with
      CL(cr) of 40-59 mL/min, 94% and 61% achieved the target C(max) and C(min24),
      respectively. Of the 8% of patients with CL(cr) of 20-39 mL/min, 83% and 15%
      achieved the target Cmax and C(min24), respectively. Nephrotoxicity, "probably"
      because of gentamicin, was observed in approximately 4% of the patients studied,
      which was irreversible in 25% of these (ie, 1% overall). CONCLUSIONS: Extending
      the dose interval of gentamicin to >24 hours is useful in patients with renal
      impairment to achieve the aims of EID. These results support initial dose
      intervals for gentamicin of 24, 36, and 48 hours for patients with CL(cr) >= 60,
      40-59, and 20-39 mL/min, respectively. Irreversible nephrotoxicity was observed
      in approximately 1% of the patients studied.

PMID- 24943064
TI  - Determination of DPYD enzyme activity in Korean population.
AB  - BACKGROUND: Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates
      the rate-limiting step in pyrimidine metabolism, especially catabolism of
      fluorouracil. This study was performed to analyze the association between DPYD
      genetic variants and DPYD enzyme activity in the Korean population. METHODS: We
      screened the genetic variants and analyzed the enzyme activity in 73 healthy
      Korean subjects (69 men and 4 women; mean age, 22.6 years). Direct sequencing was
      conducted using the ABI 3730XL system, and enzyme activity was determined using
      high-performance liquid chromatography. RESULTS: A total of 83 genetic variants
      were observed. Among the identified genetic variants, 32 were polymorphic
      including 3 core and 11 novel genetic variants. Association analysis between each
      genetic variant and enzyme activity in Korean subjects showed that 2 novel
      genetic variants, -832 G>A and -131 C>A, induced a significant difference in
      enzyme activity (P < 0.05). CONCLUSIONS: To our knowledge, this is the first
      study that has examined the association between enzyme activity and DPYD genetic
      variants in the Korean population. In this study, we identified novel genetic
      variants that are associated with the enzyme activity. These findings will be
      valuable for further pharmacogenetic studies and especially useful for
      personalized medicine.

PMID- 24943066
TI  - The artificial pancreas: a digital-age treatment for diabetes.

PMID- 24943067
TI  - Left-right asymmetry: advances and enigmas.

PMID- 24943065
TI  - Home use of closed-loop insulin delivery for overnight glucose control in adults
      with type 1 diabetes: a 4-week, multicentre, randomised crossover study.
AB  - BACKGROUND: Closed-loop insulin delivery is a promising option to improve
      glycaemic control and reduce the risk of hypoglycaemia. We aimed to assess
      whether overnight home use of automated closed-loop insulin delivery would
      improve glucose control. METHODS: We did this open-label, multicentre, randomised
      controlled, crossover study between Dec 1, 2012, and Dec 23, 2014, recruiting
      patients from three centres in the UK. Patients aged 18 years or older with type
      1 diabetes were randomly assigned to receive 4 weeks of overnight closed-loop
      insulin delivery (using a model-predictive control algorithm to direct insulin
      delivery), then 4 weeks of insulin pump therapy (in which participants used real
      time display of continuous glucose monitoring independent of their pumps as
      control), or vice versa. Allocation to initial treatment group was by computer
      generated permuted block randomisation. Each treatment period was separated by a
      3-4 week washout period. The primary outcome was time spent in the target glucose
      range of 3.9-8.0 mmol/L between 0000 h and 0700 h. Analyses were by intention to
      treat. This trial is registered with ClinicalTrials.gov, number NCT01440140.
      FINDINGS: We randomly assigned 25 participants to initial treatment in either the
      closed-loop group or the control group, patients were later crossed over into the
      other group; one patient from the closed-loop group withdrew consent after
      randomisation, and data for 24 patients were analysed. Closed loop was used over
      a median of 8.3 h (IQR 6.0-9.6) on 555 (86%) of 644 nights. The proportion of
      time when overnight glucose was in target range was significantly higher during
      the closed-loop period compared to during the control period (mean difference
      between groups 13.5%, 95% CI 7.3-19.7; p=0.0002). We noted no severe
      hypoglycaemic episodes during the control period compared with two episodes
      during the closed-loop period; these episodes were not related to closed-loop
      algorithm instructions. INTERPRETATION: Unsupervised overnight closed-loop
      insulin delivery at home is feasible and could improve glucose control in adults
      with type 1 diabetes. FUNDING: Diabetes UK.

PMID- 24943069
TI  - Agent orange exposure modeling: fallacies and errors.

PMID- 24943070
TI  - Reply to "agent Orange exposure modeling: fallacies and errors".

PMID- 24943071
TI  - Acinetobacter baumannii emerging as a multidrug-resistant skin and soft-tissue
      pathogen: parallels to methicillin-resistant Staphylococcus aureus.

PMID- 24943072
TI  - Radical S-adenosyl methionine epimerases: regioselective introduction of diverse
      D-amino acid patterns into peptide natural products.
AB  - PoyD is a radical S-adenosyl methionine epimerase that introduces multiple D
      configured amino acids at alternating positions into the highly complex marine
      peptides polytheonamide A and B. This novel post-translational modification
      contributes to the ability of the polytheonamides to form unimolecular
      minimalistic ion channels and its cytotoxic activity at picomolar levels. Using a
      genome mining approach we have identified additional PoyD homologues in various
      bacteria. Three enzymes were expressed in E. coli with their cognate as well as
      engineered peptide precursors and shown to introduce diverse D-amino acid
      patterns into all-L peptides. The data reveal a family of architecturally and
      functionally distinct enzymes that exhibit high regioselectivity, substrate
      promiscuity, and irreversible action and thus provide attractive opportunities
      for peptide engineering. 

PMID- 24943074
TI  - [Scalp neuralgia and headache elicited by cranial superficial anatomical causes:
      supraorbital neuralgia, occipital neuralgia, and post-craniotomy headache].
AB  - Most scalp neuralgias are supraorbital or occipital. Although they have been
      considered idiopathic, recent studies revealed that some were attributable to
      mechanical irritation with the peripheral nerve of the scalp by superficial
      anatomical cranial structures. Supraorbital neuralgia involves entrapment of the
      supraorbital nerve by the facial muscle, and occipital neuralgia involves
      entrapment of occipital nerves, mainly the greater occipital nerve, by the
      semispinalis capitis muscle. Contact between the occipital artery and the greater
      occipital nerve in the scalp may also be causative. Decompression surgery to
      address these neuralgias has been reported. As headache after craniotomy is the
      result of iatrogenic injury to the peripheral nerve of the scalp, post-craniotomy
      headache should be considered as a differential diagnosis. 

PMID- 24943073
TI  - Decreased global DNA methylation in the white blood cells of high fat diet fed
      vervet monkeys (Chlorocebus aethiops).
AB  - Epigenetic mechanisms are associated with the development of many chronic
      diseases and due to their reversible nature offer a unique window of opportunity
      to reverse the disease phenotype. This study investigated whether global DNA
      methylation correlates with dysglycemia in the vervet monkey (Chlorocebus
      aethiops). Diet-induced changes in DNA methylation were observed where global DNA
      methylation was twofold lower in monkeys fed a high fat diet (n = 10) compared to
      monkeys fed a standard diet (n = 15). An inverse correlation was observed between
      DNA methylation, blood glucose concentrations, bodyweight, and age, although the
      association was not statistically significant. Consumption of a high fat diet is
      associated with the development of metabolic disease; thus, these results suggest
      the use of global DNA methylation as a biomarker to assess the risk for metabolic
      disease. Moreover, this study provides further support for the use of the vervet
      monkey as a model system to study metabolic diseases such as type 2 diabetes.
      Integration of altered DNA methylation profiles into predictive models could
      facilitate risk stratification and enable intervention strategies to inhibit
      disease progression. Such interventions could include lifestyle modifications,
      for example, the increased consumption of functional foods with the capacity to
      modulate DNA methylation, thus potentially reversing the disease phenotype and
      preventing disease.

PMID- 24943075
TI  - [Clinical manifestations of 16 patients with spontaneous spinal epidural hematoma
      -stroke mimic and pitfalls for diagnosis].
AB  - Clinical manifestations of 16 patients with spontaneous spinal epidural hematoma
      were presented. We examined the point similar to that of stroke. During the
      initial visit of our hospital, the patients showed the hemiplegia in 10 cases
      (62.5%), Horner syndrome in 4 cases (25%), the painless onset in 1 case (6.3%).
      And one case showed the impairment of consciousness due to vagal reflex in severe
      pain onset, which was similar to those of subarachnoid hemorrhage. MRI images are
      useful to confirm the diagnosis. The frequent site of hematoma was the lower
      cervical spinal cord. The oval shaped hematomas shifted to the left or right in
      spinal canals, compressed spinal cords in axial image, which was a cause of
      hemiplegia. Many cases developed during active periods, and the hemorrhage might
      be relevant to oral antithrombotic agent, C hepatitis, and chronic renal failure.
      Rapidly progressive cases were indications for emergency surgery, but
      conservative therapy is also possible and was better prognosis. 

PMID- 24943076
TI  - [Lesion of intractable hiccups due to medullary infarction].
AB  - The frequency and clinical characteristics of intractable hiccups due to the
      medullary infarction is unknown. The aim of this study was to identify the
      lesions of hiccups using by brain MRI. Ninety acute medullary patients admitted
      to our stroke center within 14 days of stroke onset between April 2004 and August
      2012 were retrospectively studied. We evaluated clinical characteristics and the
      frequency of the patients causing intractable hiccups among acute medullary
      stroke patients. We divided the patients into two groups, intractable hiccups
      group, and not hiccups group. Of 90 patients, five (5.5%) had intractable
      hiccups. Hiccups group had more frequently involved right middle medullary lesion
      than not hiccups group (hiccups group vs. not hiccups group; (60% vs. 4%, p <
      0.001). In 16 cases reported the lesion of intractable hiccups, the right middle
      medullary lesion was 11 cases. We suspected that the lesion of the intractable
      hiccups was associated with the right middle medullary. 

PMID- 24943077
TI  - [Case of dermatomyositis with anti-CADM-140 antibody and alveolar hemorrhage].
AB  - A-47-year-old woman was admitted to our hospital because of eruption, severe
      arthritis, myalgia, pharyngalgia and the elevation of serum creatine kinase. She
      was diagnosed with dermatomyositis based on a biopsied specimen and clinical
      symptoms. Serum anti CADM-140 antibody was detected by immunoprecipitation. Pulse
      therapy with methylprednisolone and cyclophophamide could transiently improve
      myalgia and so on, but she died of rapidly progressive interstitial lung disease.
      Autopsy findings demonstrated diffuse alveolar damage and alveolar hemorrhage. It
      is said that patients with anti CADM-140 antibody show poor muscle symptoms and
      alveolar hemorrhage has been described very rarely. This patient is the rare case
      of dermatomyositis with anti CADM-140 antibody developing severe muscle symptoms,
      pharyngalgia and aleveolar hemorrhage in autopsy findings. 

PMID- 24943078
TI  - [Case of ataxic sensory neuronopathy associated with Sjogren's syndrome].
AB  - A 71-year-old woman developed advanced thermal hypoalgesia, bathyesthesia, and
      significant sensory ataxia 1 year ago. She also had difficulty maintaining a
      sitting posture. Patchy and reduced thermal nociception corresponding to a
      dermatome was found in her four extremities and trunk. On the basis of several
      tests, she was diagnosed with ataxic sensory neuronopathy due to dorsal root
      ganglionitis associated with Sjogren's syndrome. Generally, dorsal root
      ganglionitis associated with Sjogren's syndrome is refractory. After treatment
      with simple plasmapheresis, she was able to maintain a sitting posture. Finally,
      her symptoms stabilized after the inclusion of oral D-penicillamine to her
      treatment regimen. Although the clinical course was observed for about one year,
      we report this case because of its valuable finding, i.e., her symptoms improved
      after simple plasmapheresis and oral administration of D-penicillamine. 

PMID- 24943079
TI  - [Familial progressive external opthalmoplegia, parkinsonism and polyneuropathy
      associated with POLG1 mutation].
AB  - Multiple mitochondrial DNA (mtDNA) deletions usually occur secondarily to a
      mutation in one of the enzymes involved in mtDNA maintenance, such as polymerase
      gamma, which is encoded by the nuclear polymerase gamma1 gene (POLG1) and POLG2.
      Patients with multiple mtDNA deletion disorders show clinical heterogeneity of
      symptoms, in addition to usually seen progressive external ophthalmoplegia (PEO).
      We conducted clinical, histological and genetic analyses of two affected sisters
      in a family with the autosomal dominant inheritance pattern of PEO. A 73-year-old
      woman (patient 1) with congenital hypogonadism and PEO developed L-dopa
      responsive parkinsonism about the age of 60. Neurological examination revealed
      mild proximal muscle weakness and polyneuropathy too. Her 69-year-old sister
      (patient 2) also showed PEO, parkinsonism and polyneuropathy. Histopathological
      studies of biopsied muscle specimens from patient 1 revealed numerous ragged red
      fibers as well as fibers with increased succinate dehydrogenase activity and
      decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected,
      both by Southern blot and long-range PCR assays of total DNA from the biopsied
      muscle specimens. A systemic mutational analysis in both sisters revealed a
      heterozygous p.Y955C (c.2864A>G) mutation in POLG1. This is the first Japanese
      family identified with this mutation. We reviewed cases with this mutation
      highlighting a wide phenotypic spectrum of this disorder. 

PMID- 24943080
TI  - [Two cases of stroke associated with the use of finasteride, an approved drug for
      male-pattern hair loss in Japan].
AB  - We report two cases of stroke associated with the use of finasteride at 1 mg/day,
      which is approved in Japan for the treatment of male-pattern hair loss. The first
      case involved a 35-year-old male taking 1 mg of finasteride daily for 6 months to
      prevent male-pattern hair loss. He was taken to a hospital and later admitted to
      our hospital owing to headache and seizures. Brain computed tomography (CT)
      images showed a low-density area in the right frontal lobe. CT venography (CTV)
      revealed sinus thrombosis and he was treated with an anticoagulant. As the
      headache gradually subsided, medications were tapered and terminated 10 months
      later when venous flow to the sagittal sinus and left transverse sinus was
      confirmed to be recanalized. The second case involved a 41-year-old male taking 1
      mg of finasteride and 6 mg of minoxidil daily for 1 year for male-pattern hair
      loss. He started having headaches and was admitted to our hospital when diffusion
      weighted images of brain magnetic resonance imaging (MRI) showed a high-intensity
      area in the left parietotemporal lobe. He was treated with antiplatelet and
      anticoagulation medicines. The Japan Pharmaceutical and Medical Devices Agency
      (PMDA) has reported 14 cases of thrombosis in patients taking finasteride in
      Japan; 4 cases of stroke (our 2 cases and 2 reported by PMDA), 6 cases of
      myocardial infarction, and 4 cases of other thrombotic diseases. Increases in
      estrone and estradiol levels in prostate cancer patients and controls receiving 5
      mg of finasteride have been reported. Gynecomastia has also been reported as one
      of the adverse effects of finasteride at 1 mg or 5 mg daily. Taken together, we
      assume that the increases in estrone and estradiol levels induced by finasteride
      lead to thrombosis development. 

PMID- 24943081
TI  - [Case of CNS-limited ANCA-associated vasculitis presenting as recurrent ischemic
      stroke].
AB  - A 73-year-old man was admitted to our hospital because of a decrease in
      spontaneity. His medical history included two stroke episodes, probably related
      to hypertension. Brain MRI on admission demonstrated acute infarction in the
      right caudate nucleus and left putamen. Intravenous infusion of a low molecular
      weight heparin added to oral antiplatelets was started. Following admission, he
      developed a low grade fever and severe inflammatory reaction. The focus of
      infection was not evident, and none of the antibiotics tried were effective. Ten
      days after admission, he developed right hemiparesis, and an additional brain MRI
      showed new multiple infarctions. We also determined the presence of a high MPO
      ANCA titer (57 EU), and we diagnosed the patient's condition to be ANCA
      associated vasculitis (AAV). Steroid therapy improved his inflammatory reaction
      and stroke recurrence was not observed. We suggest that vasculitis should be
      considered as a potential risk factor for repeated small infarctions with fever
      of unknown origin, especially those of perforating artery territories. 

PMID- 24943082
TI  - [Normokalemic periodic paralysis lasting for two weeks: a severe form of sodium
      channelopathy with M1592V mutation].
AB  - A 73-year-old man with recurrent periodic paralytic episodes lasting for two
      weeks each admitted to our hospital because of the leg weakness and the elevated
      value of serum creatine kinase. On admission, weakness in the proximal legs and
      mild eye lid myotonia were noted. Needle electromyography revealed abundant
      myotonic discharges. The prolonged exercise test showed a continuous reduction of
      compound muscle action potentials in the abductor digiti minimi muscle. Direct
      sequencing of SCN4A in the proband showed a G-to-A alteration at position 4774
      that results in a change of 1592(nd) methionine to valine (M1592V). Cosegregation
      regarding the M1592V mutation and paralytic phenotype in this family was
      confirmed. Two cardinal features in this family were longer paralytic episodes
      compared to classical hyperkalemic/normokalemic periodic paralysis and the normal
      potassium value during the paralytic episodes. This study together with
      antecedent reports indicates that M1592V mutation shares a much greater clinical
      diversity ranging from congenital paramyotonia to periodic paralysis with a
      longer duration. 

PMID- 24943083
TI  - [Ischemic stroke in a young woman of Turner syndrome with T1-weighted imaging
      pulvinar sign].
AB  - A 39-year-old woman developed right hemiparesis in a few days. Magnetic resonance
      images revealed cerebral infarction in the territory of the left lenticulostriate
      artery, and MR angiography showed severe stenosis of the middle and anterior
      cerebral arteries and moderate one of the vertebral arteries. Bilateral and
      symmetric T1 hyperintensity in the pulvinar (T1-weighted imaging-pulvinar sign;
      "T1 pulvinar sign") was detected, which is recognized as a key imaging of Fabry
      disease. The alpha-galactosidase A gene analysis, however, showed no mutation.
      Although specific physical symptoms were solely short stature and oligomenorrhea,
      the diagnosis of Turner syndrome was confirmed by the chromosome analysis which
      showed mosaicism of 45XO and 46X,r(X) (60%:40%). To our knowledge, this is the
      first report of Turner syndrome with "T1 pulvinar sign". 

PMID- 24943084
TI  - [The proceedings of the 2013 Kinki Regional Post Graduate Education Meeting].

PMID- 24943085
TI  - [The proceedings of the 207th Kanto-Koshinetsu Regional Meeting of the Japanese
      Society of Neurology].

PMID- 24943088
TI  - Medical clowns ease anxiety and pain perceived by children undergoing allergy
      prick skin tests.
AB  - BACKGROUND: Intervention of medical clowns (MC) during various medical procedures
      performed in children has been used to relieve anxiety and pain. Their role in
      allergy skin testing has never been evaluated. OBJECTIVE: To evaluate whether MC
      can diminish pain and anxiety perceived by children undergoing allergy skin prick
      tests (SPT). METHODS: In a prospective, randomized, controlled, and blinded
      study, children undergoing SPT were or were not accompanied by MC. All parents
      and children >=8 years completed the State-Trait Anxiety Inventory (STAI) before
      and after SPT. Videotapes recorded during the procedure were scored for anxiety
      (m-YPAS) for all children and for pain (FLACC) for children 2-7 years old by a
      psychologist who was unaware of the MC's presence. After SPT, children >=8 years
      completed a visual analog score (VAS) for pain. RESULTS: Ninety-one children
      (mean age 8.2 years, M/F = 54/37) were recruited of whom 45 were accompanied by
      clowns. A significant reduction in state-STAI was found in the clowns group, in
      both parents and children, when compared with the regular group (26.9 +/- 6.6 and
      32.3 +/- 10.0; P = 0.004, and 27.1 +/- 4.2 and 34.3 +/- 7.6; P = 0.002,
      respectively). Both m-YPAS and FLACC were reduced in the clowns group compared
      with the regular one. In the clowns group, m-YPAS positively correlated with both
      VAS and FLACC (P = 0.000 and 0.002, respectively). m-YPAS was positively
      correlated with FLACC in the regular group (P = 0.000). CONCLUSION: Medical
      clowns significantly decrease the level of anxiety perceived by both children
      undergoing allergy SPT and their parents, as well as the pain perceived by young
      children.

PMID- 24943089
TI  - A metagenetic approach for revealing community structure of marine planktonic
      copepods.
AB  - Marine planktonic copepods are an ecologically important group with high species
      richness and abundance. Here, we propose a new metagenetic approach for revealing
      the community structure of marine planktonic copepods using 454 pyrosequencing of
      nuclear large subunit ribosomal DNA. We determined an appropriate similarity
      threshold for clustering pyrosequencing data into molecular operational taxonomic
      units (MOTUs) using an artificial community containing 33 morphologically
      identified species. The 99% similarity threshold had high species-level
      resolution for MOTU clustering but overestimated species richness. The artificial
      community was appropriately clustered into MOTUs at 97% similarity, with little
      inflation in MOTU numbers and with relatively high species-level resolution. The
      number of sequence reads of each MOTU was correlated with dry weight of that
      taxon, suggesting that sequence reads could be used as a proxy for biomass. Next,
      we applied the method to field-collected samples, and the results corresponded
      reasonably well with morphological analysis of these communities. Numbers of
      MOTUs were well correlated with species richness at 97% similarity, and large
      numbers of sequence reads were generally observed in MOTUs derived from species
      with large biomass. Further, MOTUs were successfully classified into taxonomic
      groups at the family level at 97% similarity; similar patterns of species
      richness and biomass were revealed within families with metagenetic and
      morphological analyses. At the 99% similarity threshold, MOTUs with high
      proportions of sequence reads were identified as biomass-dominant species in each
      field-collected sample. The metagenetic approach reported here can be an
      effective tool for rapid and comprehensive assessment of copepod community
      structure.

PMID- 24943090
TI  - Xeroderma pigmentosum in the United kingdom.
AB  - The seminal discovery by James Cleaver of defective DNA repair in xeroderma
      pigmentosum (XP) opened up an ever-expanding field of DNA repair-related
      disorders. In addition, it put XP on the map and has led to improved diagnosis,
      care and management of affected patients. In the United Kingdom, we recently
      established a multidisciplinary specialist clinic for XP patients. All XP
      patients in the United Kingdom are able to visit the clinic where they are
      examined and advised by a team of specialists with detailed knowledge of the
      different aspects of XP. 

PMID- 24943091
TI  - Pd(II)-Catalyzed arylation of unactivated methylene C(sp3)-H bonds with aryl
      halides using a removable auxiliary.
AB  - A Pd(II)-catalyzed arylation of methylene C(sp(3))-H bonds in aliphatic amides
      directed by our newly developed PIP directing group with aryl iodides/bromides
      has been achieved. Arylation occurs efficiently with a broad range of aryl
      halides and amides.

PMID- 24943093
TI  - Macrophage-derived delta-like protein 1 enhances interleukin-6 and matrix
      metalloproteinase 3 production by fibroblast-like synoviocytes in mice with
      collagen-induced arthritis.
AB  - OBJECTIVE: We previously reported that blockade of the Notch ligand delta-like
      protein 1 (DLL-1) suppressed osteoclastogenesis and ameliorated arthritis in a
      mouse model of rheumatoid arthritis (RA). However, the mechanisms by which joint
      inflammation were suppressed have not yet been revealed. This study was
      undertaken to determine whether DLL-1 regulates the production of RA-related
      proinflammatory cytokines. METHODS: Joint cells from mice with collagen-induced
      arthritis (CIA) and mouse fibroblast-like synoviocytes (FLS) were cultured with
      or without stimuli in the presence of neutralizing antibodies against Notch
      ligands, and the production of proinflammatory cytokines was determined by enzyme
      linked immunosorbent assay. The expression of Notch receptors and ligands on
      mouse joint cells was determined by flow cytometry. RESULTS: The production of
      interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) by mouse joint cells with or without stimulation was suppressed by DLL-1
      blockade. DLL-1 blockade also suppressed the levels of IL-6 and matrix
      metalloproteinase 3 (MMP-3) in the joint fluid in a mouse model of RA. However,
      the production of tumor necrosis factor alpha and IL-1beta was not suppressed by
      DLL-1 blockade. The production of IL-6 and MMP-3 by mouse FLS was enhanced by DLL
      1 stimulation as well as Notch-2 activation. Among joint cells, DLL-1 was not
      expressed on mouse FLS but was expressed on macrophages. CONCLUSION: These
      results suggest that the interaction of DLL-1 on mouse joint macrophages with
      Notch-2 on mouse FLS enhances the production of IL-6 and MMP-3. Therefore,
      suppression of IL-6, GM-CSF, and MMP-3 production by DLL-1 blockade might be
      responsible for the amelioration of arthritis in a mouse model of RA.

PMID- 24943092
TI  - Analytical interference in serum iron determination reveals iron versus
      gadolinium transmetallation with linear gadolinium-based contrast agents.
AB  - OBJECTIVES: The purposes of this study were to evaluate the risk for analytical
      interference with gadolinium-based contrast agents (GBCAs) for the colorimetric
      measurement of serum iron (Fe3+) and to investigate the mechanisms involved.
      MATERIALS AND METHODS: Rat serum was spiked with several concentrations of all
      molecular categories of GBCAs, ligands, or "free" soluble gadolinium (Gd3+).
      Serum iron concentration was determined by 2 different colorimetric methods at pH
      4.0 (with a Vitros DT60 analyzer or a Cobas Integra 400 analyzer). Secondly, the
      cause of interference was investigated by (a) adding free soluble Gd3+ or Mn2+ to
      serum in the presence of gadobenic acid or gadodiamide and (b) electrospray
      ionization mass spectrometry. RESULTS: Spurious decrease in serum Fe3+
      concentration was observed with all linear GBCAs (only with the Vitros DT60
      technique occurring at pH 4.0) but not with macrocyclic GBCAs or with free
      soluble Gd3+. Spurious hyposideremia was also observed with the free ligands
      present in the pharmaceutical solutions of the linear GBCAs gadopentetic acid and
      gadodiamide (ie, diethylene triamine pentaacetic acid and calcium-diethylene
      triamine pentaacetic acid bismethylamide, respectively), suggesting the formation
      of Fe-ligand chelate.Gadobenic acid-induced interference was blocked in a
      concentration-dependent fashion by adding a free soluble Gd3+ salt. Conversely,
      Mn2+, which has a lower affinity than Gd3+ and Fe3+ for the ligand of gadobenic
      acid (ie, benzyloxypropionic diethylenetriamine tetraacetic acid), was less
      effective (interference was only partially blocked), suggesting an Fe3+ versus
      Gd3+ transmetallation phenomenon at pH 4.0. Similar results were observed with
      gadodiamide. Mass spectrometry detected the formation of Fe-ligand with all
      linear GBCAs tested in the presence of Fe and the disappearance of Fe-ligand
      after the addition of free soluble Gd3+. No Fe-ligand chelate was found in the
      case of the macrocyclic GBCA gadoteric acid. CONCLUSIONS: Macrocyclic GBCAs
      induced no interference with colorimetric methods for iron determination, whereas
      negative interference was observed with linear GBCAs using a Vitros DT60
      analyzer. This interference of linear GBCAs seems to be caused by the excess of
      ligand and/or an Fe3+ versus Gd3+ transmetallation phenomenon.

PMID- 24943094
TI  - Up-regulation of brain-enriched miR-107 promotes excitatory neurotoxicity through
      down-regulation of glutamate transporter-1 expression following ischaemic stroke.
AB  - Recent studies have uncovered that accumulation of glutamate after ischaemic
      stroke is closely associated with the down-regulation of glutamate transporter-1
      (GLT-1) expression, suggesting that GLT-1 expression critically controls
      glutamate accumulation and the abnormal glutamate transport-elicited neuronal
      cell excitotoxicity in patients with ischaemic stroke. However, it remains
      unknown how GLT-1 expression is regulated under ischaemic stroke conditions. In
      the present study, we screened the expression of nine brain-specific or brain
      enriched miRNAs in a focal cerebral ischaemia/reperfusion (I/R) injury rat model,
      which showed glutamate accumulation and down-regulated GLT-1 expression as
      expected, and revealed that the miR-107 level was elevated in both brain tissue
      and plasma in the model. Next, we examined the functional relationship of miR-107
      with GLT-1 expression in a nerve cell hypoxia/reoxygenation (H/R) injury model.
      H/R treatment increased apoptosis of the nerve cells concomitant with glutamate
      accumulation, miR-107 elevation and suppressed GLT-1 expression, mimicking our in
      vivo findings in the cerebral I/R injury rat model in vitro. Co-treating the
      cells with an miR-107 inhibitor blocked all of the effects, demonstrating that
      miR-107 functions to inhibit GLT-1 expression and elevate glutamate accumulation.
      To extend these animal and cell-based studies to clinical patients, we measured
      the plasma levels of miR-107 and glutamate, and observed that both miR-107 and
      glutamate were elevated in patients with ischaemic stroke. On the basis of these
      observations, we conclude that elevated miR-107 expression after ischaemic stroke
      accounts, at least partially, for glutamate accumulation through suppression of
      GLT-1 expression. Our findings also highlight that the plasma level of miR-107
      may serve as a novel biomarker for monitoring excitotoxicity in patients with
      ischaemic stroke. 

PMID- 24943095
TI  - Small intestinal permeability is increased in diarrhoea predominant IBS, while
      alterations in gastroduodenal permeability in all IBS subtypes are largely
      attributable to confounders.
AB  - BACKGROUND: Intestinal permeability has been studied in small groups of IBS
      patients with contrasting findings. AIMS: To assess intestinal permeability at
      different sites of the GI tract in different subtypes of well-characterised IBS
      patients and healthy controls (HC), and to assess potential confounding factors.
      METHODS: IBS patients and HC underwent a multi-sugar test to assess site-specific
      intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h
      urine indicated gastroduodenal and small intestinal permeability, respectively.
      Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and
      colonic permeability, respectively. Linear regression analysis was used to assess
      the association between IBS groups and intestinal permeability and to adjust for
      age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of
      medication. RESULTS: Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS
      M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was
      significantly increased in the total IBS group [MUmol, median (Q1;Q3): 5.26
      (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs.
      HC. However, differences attenuated when adjusting for confounders. The
      lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs.
      0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for
      confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol
      ratio between groups. CONCLUSIONS: Small intestinal permeability is increased in
      patients with IBS-D compared to healthy controls, irrespective of confounding
      factors. Adjustment for confounders is necessary when studying intestinal
      permeability, especially in a heterogeneous disorder such as IBS.

PMID- 24943096
TI  - Education and support for self care management in chronic illnesses in India.

PMID- 24943097
TI  - Evidence for peroxidase activity in Caralluma umbellata.
AB  - Vast applications of peroxidases create an increasing demand to characterize
      peroxidases from new sources with more applicability potential. The aim of the
      present study was to check the presence of peroxidase activity from Caralluma
      umbellata. This is the first report on the C. umbellata peroxidase (CUP). The
      presence of peroxidase was revealed by the histochemical analysis of the stem
      sections, zymographic studies, and in vitro peroxidase activity assay using
      various reducing substrates viz., 2, 2'-azinobis (3-ethylbenzthiazoline-6
      sulfonic acid) (ABTS), guaiacol, o-dianisidine, and ferulic acid. The band
      pattern in zymogram confirms that CUP has a molecular weight less than that of
      horseradish peroxidase (44 kDa). Comparative evaluation of peroxidase activity of
      CUP with respect to horseradish peroxidase (HRP) indicates that CUP catalyzes
      ABTS and ferulic acid in a similar pattern as HRP but with guaiacol, the extent
      of catalysis shown by CUP over HRP is high. The standard inhibitors sodium azide
      and sodium meta bisulphite inhibited CUP activity in a dose dependent manner.

PMID- 24943098
TI  - Long-term effectiveness and safety of nabiximols
      (tetrahydrocannabinol/cannabidiol oromucosal spray) in clinical practice.
AB  - BACKGROUND: Nabiximols (Sativex(r)), in a cannabinoid-based oromucosal spray, is
      an add-on therapy option for patients with moderate to severe multiple sclerosis
      spasticity (MSS) resistant to other medications. The study objective was to
      provide long-term data on clinical outcomes, tolerability, quality of life and
      treatment satisfaction for MSS patients receiving nabiximols in routine care.
      METHODS: This was the 12-month prolongation of the MOVE 2 study, an
      observational, prospective, multi-centre 3-month non-interventional study
      conducted in a routine care setting across Germany. Structured documentation
      forms, questionnaires and validated instruments were used for data collection.
      RESULTS: In total, 52 patients were included in the effectiveness analysis after
      12 months. The mean spasticity numerical rating scale (NRS, 0-10) score decreased
      significantly from 6.0 +/- 1.8 points at MOVE 2 baseline to 4.8 +/- 1.9 points
      after 1 month and remained on this level after 12 months (4.5 +/- 2.0 points); in
      patients classified as 'initial responders' (>=20% NRS improvement after 1 month)
      similar results were found (baseline: 6.3 +/- 1.4 points; after 1 month: 4.0 +/-
      1.0 points; after 12 months: 4.3 +/- 1.9 points). The majority of patients (84%)
      did not report adverse events. CONCLUSION: Real-life data confirm the long-term
      effectiveness and tolerability of nabiximols for the treatment of resistant MSS
      in everyday clinical practice.

PMID- 24943099
TI  - Analyses of the binding between Theileria orientalis major piroplasm surface
      proteins and bovine red blood cells.

PMID- 24943100
TI  - Risk factors for faecal colonisation with Escherichia coli producing extended
      spectrum and plasmid-mediated AmpC beta-lactamases in dogs.
AB  - The aim of this study was to assess the prevalence and risk factors for faecal
      carriage of extended-spectrum beta-lactamase (ESBL) and plasmidic AmpC beta
      lactamase (pAmpC) Escherichia coli producers in dogs. A three-month cross
      sectional study was conducted and 151 rectal swabs were obtained from healthy
      dogs. ESBL and pAmpC genes were detected by PCR and were sequenced. Logistic
      regression models were used to investigate risk factors for the carriage of ESBL
      and pAmpC-producing E. coli. About 15 per cent of the isolates carried ESBL genes
      (blaCTX-M-32 n=8, blaCTX-M-15 n=5, blaCTX-M-1 n=3, blaCTX-M-9-like n=4) and 20
      per cent carried pAmpC genes (blaCMY-2 n=23, blaCMY-2-like n=2). Thirteen dogs
      carried an E. coli isolate with both an ESBL and a pAmpC gene. One E. coli
      isolate harboured the human blaDHA-1 pAmpC gene, which has not been previously
      reported in companion animals in Europe. Dogs with a history of antimicrobial
      therapy in the past year had a higher risk of being carriers of ESBL-producing
      (P=0.003, OR =7.85) and pAmpC-producing (P=0.005, OR=6.28) E. coli. Dogs from
      shelter/breeders were approximately three times more likely to have an ESBL- or a
      pAmpC-producing E. coli than dogs from private owners. Males have a reduced risk
      of carrying a pAmpC-producing E. coli than females (P=0.017, OR =0.28). The
      knowledge of potential risk factors may help to limit the impact of resistance
      through implementation of effective control measures and judicious antimicrobial
      therapy.

PMID- 24943101
TI  - Use of a rotary battery-powered device for the collection of bone marrow in dogs
      and cats.
AB  - Bone marrow biopsies form an important part of investigations into a large number
      of conditions in veterinary patients. In the human field, powered drivers
      specifically designed for the collection of bone marrow have become available.
      These systems have been shown to obtain better quality bone marrow, more quickly
      and with less pain. This study showed that a powered rotary bone marrow
      collection system could be used in dogs and cats to collect bone marrow, easily
      and without complications. Good quality bone marrow aspirates were obtained in
      the majority of patients; where aspirates could not be collected it was not
      possible to obtain aspirates from alternative sites using a standard manual
      technique. Bone marrow core samples were of increased size (mean useable area
      16.5 mm(2)), compared to samples obtained using a standard manual technique (mean
      useable area 4.1 mm(2), P<0.001). Samples obtained using the powered system were
      also judged to be of significantly better diagnostic quality. The use of a
      powered system for bone marrow collection may aid the collection of better
      quality bone marrow samples in small animal patients.

PMID- 24943102
TI  - Chronic pulmonary aspergillosis: an update on diagnosis and treatment.
AB  - Chronic pulmonary aspergillosis (CPA) affects individuals with non-systemic or
      mildly systemic immunodepression or altered pulmonary integrity due to underlying
      disease. It has been reported with a variety of clinical and radiological
      patterns. The condition should be distinguished from simple aspergilloma and
      allergic bronchopulmonary aspergillosis as well as invasive aspergillosis in
      severely immunocompromised patients. CPA generally requires long-term antifungal
      treatment and surgery may be considered. Life-threatening haemoptysis may be
      prevented by bronchial arteriography with embolisation. However, currently there
      are no documented treatment recommendations for CPA. This review provides an up
      to-date practical overview of this condition, including a comprehensive update on
      diagnosis and management.

PMID- 24943103
TI  - Small expression tags enhance bacterial expression of the first three
      transmembrane segments of the apelin receptor.
AB  - G-protein coupled receptors (GPCRs) are inherently dynamic membrane protein
      modulators of various important cellular signaling cascades. The apelin receptor
      (AR or APJ) is a class A GPCR involved in numerous physiological processes,
      implicated in angiogenesis during tumour formation and as a CD4 co-receptor for
      entry of human immunodeficiency virus type 1 (HIV-1) to cells. Due to the lack of
      efficient methods to produce full-length GPCRs enriched with nuclear magnetic
      resonance (NMR) active (15)N, (13)C, and (or) (2)H isotopes, small GPCR fragments
      typically comprising 1-2 transmembrane segments are frequently studied using NMR
      spectroscopy. Here, we report successful overexpression of transmembrane segments
      1-3 of AR (AR_TM1-3) in the C41(DE3) strain of Escherichia coli using an AT-rich
      gene tag previously reported to enhance cell-free expression yields. The
      resulting protein, with 6 additional N-terminal residues due to the expression
      tag, was purified using high-performance liquid chromatography (HPLC). Far UV
      circular dichroism spectropolarimetry demonstrates that AR_TM1-3 has the
      predicted ~40% alpha-helical character in membrane-mimetic environments. (1)H
      (15)N HSQC NMR experiments imply amenability to high-resolution NMR structural
      characterization and stability in solution for weeks. Notably, this small
      expression tag approach may also be generally applicable to other membrane
      proteins that are difficult to express in E. coli.

PMID- 24943104
TI  - Synthesis and evaluation of thalidomide and phthalimide esters as antitumor
      agents.
AB  - A series of thalidomide and phthalimide ester analogs were efficiently
      synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2
      bromoethyl)phthalimide derivatives with various biologically important carboxylic
      acids. The synthesized compounds were purified and characterized by various
      chromatographic and spectroscopic techniques. The antitumor activity of all the
      synthesized compounds was screened against human liver and breast cancer cells,
      which showed that phthalimide ester 6a was the best cytotoxic compound against
      MCF7 cells, while all of the tested compounds showed a non-cytotoxic effect
      against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect,
      while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect.
      Meanwhile, estimation of the binding affinity for all the synthesized compounds
      toward the vascular endothelial growth factor receptor (VEGFR) showed that
      compounds 5a, 5b, and 7d were the most potent inhibitors. 

PMID- 24943106
TI  - Zeatin modulates flower bud development and tocopherol levels in Cistus albidus
      (L.) plants as they age.
AB  - In a previous study we showed that Cistus albidus (L.) experiences an age
      dependent decay in flower vigour correlated with a decline in trans-zeatin (tZ)
      levels. In the present study we aimed to establish a causal relationship between
      these two phenomena. Exogenous tZ applied to plants grown under semi-controlled
      conditions did not rescue flower vigour; however, it accelerated flower
      development, but only in younger individuals. Older plants showed lower
      tocopherol levels in flower buds, which were restored by exogenous tZ, suggesting
      that a loss of antioxidant defences may underlie the age-dependent decay in
      flower vigour. We conclude that declining tZ levels may not be directly
      responsible for the age-associated loss of floral vigour; that tZ modulates the
      speed of flower development as plants age; and that flower buds alter their
      sensitivity to tZ as plants age. 

PMID- 24943105
TI  - A randomised, double-blind study of polyethylene glycol 4000 and lactulose in the
      treatment of constipation in children.
AB  - BACKGROUND: Chronic constipation is frequent in children. The objective of this
      study is to compare the efficacy and safety of PEG 4000 and lactulose for the
      treatment of chronic constipation in young children. METHODS: This randomised,
      double-blind study enrolled 88 young children aged 12 to 36 months, who were
      randomly assigned to receive lactulose (3.3 g per day) or PEG 4000 (8 g per day)
      for four weeks. The primary efficacy variable was stool frequency during the
      fourth week of treatment. Secondary outcomes were the number and frequency of
      subjective symptoms associated with defecation at each visit. RESULTS: Stool
      frequency was comparable in the two groups at baseline (lactulose: 0.7 +/- 0.5;
      PEG 4000: 0.5 +/- 0.55). Mean stool frequency increased from 0.70 +/- 0.50
      stools/day at baseline to 0.80 +/- 0.41 at Week 4 in the lactulose group and from
      0.50 +/- 0.55 to 1.10 +/- 0.55 stools/day in the PEG 4000 group. A significant
      difference was observed in the adjusted mean change from baseline, which was 0.15
      stools/day in the lactulose group and 0.51 stools/day in the PEG 4000 group, with
      a least-squares mean difference of 0.36 stools/day [95% CI: 0.16 to 0.56]. With
      respect to secondary outcome variables, stool consistency and ease of stool
      passage improved more in the PEG 4000 group (p = 0.001). The incidence of adverse
      events was similar in both groups, the majority of which were mild. CONCLUSIONS:
      PEG 4000 has superior efficacy to lactulose for the treatment of chronic
      constipation in young children and is well tolerated. TRIAL REGISTRATION: US
      National Institute of Health Clinical Trials database; study NCT00255372 first
      registered 17th November 2005.

PMID- 24943107
TI  - Double hit lymphoma: the MD Anderson Cancer Center clinical experience.
AB  - We report our experience with 129 cases of double hit lymphoma (DHL), defined as
      B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2
      and/or BCL6. All cases were reviewed for histopathological classification. Median
      age was 62 years (range, 18-85), 84% of patients had advanced-stage disease, and
      87% had an International Prognostic Index score >=2. Fourteen patients (11%) had
      a history of low-grade follicular lymphoma. MYC translocation was present in 81%,
      and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present
      in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival
      (EFS) rates in all patients and patients who received R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab,
      etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R
      HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were
      33%, 25%, 67% and 32%, respectively. In patients achieving complete response with
      initial therapy (n = 71), 2-year EFS rates in patients who did (n = 23) or did
      not (n = 48) receive frontline stem cell transplantation were 68% and 53%,
      respectively (P = 0.155). The cumulative incidence of central nervous system
      involvement was 13% at 3 years. Multivariate analysis identified performance
      status >=2 and bone marrow involvement as independent adverse prognostic factors
      for EFS and OS. Further research is needed to identify predictive and/or
      targetable biological markers and novel therapeutic approaches for DHL patients. 

PMID- 24943109
TI  - Reversed scan direction reduces electron beam damage in EBSD maps.
AB  - The deleterious effects of electron beam damage on high-resolution electron
      backscatter diffraction (EBSD) maps of undeformed quartz are significantly
      reduced by scanning in the direction opposite to that dictated by widely used
      EBSD acquisition software. Higher quality electron backscatter patterns are
      produced when the electron beam moves progressively down the sample (the apparent
      'up' direction in the resulting maps) for all step sizes where beam damage
      affects EBSD map quality (<= ~0.4 MUm in this study). The relative improvement
      associated with downward scanning increases as step size is reduced. A comparison
      of high-resolution maps made in experimentally deformed quartz demonstrates that
      downward scanning reduces by a factor of ~2 the lower limit in step size relative
      to maps scanned in the conventional direction. The electron beam damages quartz
      at its point of entry, forming ~0.1-MUm diameter bumps visible in Scanning
      electron microscope (SEM) images. Downward scanning produces better results
      because it minimizes the flux of electrons through these loci of damaged crystal.

PMID- 24943108
TI  - Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve
      growth performance and productivity in post-weaning pigs.
AB  - BACKGROUND: Immunoregulatory probiotics (immunobiotics) have been proposed to
      improve piglets' immune system to avoid intestinal infections and reduce
      unproductive inflammation after weaning. Previously, it was demonstrated that
      Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response
      triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal
      epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer's
      patches (PP). OBJECTIVE: In view of the critical importance of PIE-APCs
      interactions in the regulation of intestinal immune responses, we aimed to
      examine the effect of LjTL2937 on activation patterns of APCs from swine PPs in
      co-cultures with PIE cells. In addition, we investigated whether LjTL2937 was
      able to beneficially modulate intestinal immunity of piglets after weaning to
      improve immune-health status. RESULTS: Stimulation of PIE-APCs co-cultures with
      LjTL2937 increased the expression of MHC-II, CD80/86, IL-10, and Bcl-3 in
      CD172a+CD11R1- and CD172a+CD11R1high APCs. In addition, the TL2937 strain caused
      the upregulation of three negative regulators of TLR4 in PIE cells: MKP-1, Bcl-3
      and A20. These changes significantly reduced the inflammatory response triggered
      by TLR4 activation in PIE-APCs co-cultures. The in vivo experiments using
      castrated male piglets (crossbreeding (LWD) with Landrace (L), Large Yorkshire
      (W) and Duroc (D))of 3 weeks of age demonstrated that feeding with LjTL2937
      significantly reduced blood complement activity and C reactive protein
      concentrations while no changes were observed in blood leukocytes, ratio of
      granulocytes to lymphocyte numbers, macrophages' activity and antibody levels. In
      addition, treatment with LjTL2937 significantly improved growth performance and
      productivity, and increased carcass quality. CONCLUSIONS: We demonstrated that
      the use of immunobiotics strains like LjTL2937, as supplemental additives for
      piglets feedings, could be used as a strategy to maintain and improve intestinal
      homeostasis; that is important for the development of the pig and for health and
      performance throughout the productive life of the animal.

PMID- 24943110
TI  - Quantitative determination and validation of avermectin B1a in commercial
      products using quantitative nuclear magnetic resonance spectroscopy.
AB  - Nuclear magnetic resonance is defined as a quantitative spectroscopic tool that
      enables a precise determination of the number of substances in liquids as well as
      in solids. There is few report demonstrating the application of NMR in the
      quantification of avermectin B1a (AVB1a ); here, a proton nuclear magnetic
      resonance spectroscopy ((1) H NMR) using benzene [1-methoxy-4-(2-nitroethyl)
      (PMN)] as an internal standard and deuterochloroform as an NMR solvent was tested
      for the quantitative determination of AVB1a . The integrated signal of AVB1a at
      5.56 ppm and the signal of PMN at 8.14 ppm in the (1) H NMR spectrum were used
      for quantification purposes. Parameters of specificity, linearity, accuracy,
      precision, intermediate precision, range, limit of detection (LOD), limit of
      quantification (LOQ), stability and robustness were validated. The established
      method was accurate and precise with good recovery (98.86%) and relative standard
      deviation (RSD) of assay (0.34%) within the linearity of the calibration curve
      ranging from 5.08 to 13.58 mg/ml (R(2)  = 0.9999). The LOD and LOQ were 0.009 and
      0.029 mg/ml, which indicated the excellent sensitivity of the method. The
      stability of the method was testified by a calculated RSD of 0.11%. The
      robustness was testified by modification of four different parameters, and the
      differences among each parameter were all less than 0.1%. Comparing with the
      assay described by the manufacturer of avermectin tablets, there was no
      significant difference between the assay obtained by HPLC and quantitative NMR
      (qNMR), which indicated qNMR was a simple and efficient method for the
      determination of AVB1a in commercial formulation products.

PMID- 24943111
TI  - Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by
      modulating function of signal transducer and activator of transcription factors.
AB  - Hepatitis A virus (HAV) infection is the major cause of acute liver failure in
      paediatric patients. The clinical spectrum of infection is variable, and liver
      injury is determined by altered hepatic enzyme function and bilirubin
      concentration. We recently reported differences in cytokine profiles between
      distinct HAV-induced clinical courses, and bilirubin has been recognized as a
      potential immune-modulator. However, how bilirubin may affect cytokine profiles
      underlying the variability in the course of infection has not been determined.
      Herein, we used a transcription factor (TF) binding site identification approach
      to retrospectively analyse cytokine expression in HAV-infected children and to
      predict the entire set of TFs associated with the expression of specific cytokine
      profiles. The results suggested that modulation of the activity of signal
      transducers and activators of transcription proteins (STATs) may play a central
      role during HAV infection. This led us to compare the degree of STAT
      phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric
      patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera
      were associated with increased STAT-1 and STAT-5 phosphorylation. A positive
      correlation was observed between the serum interleukin-6 (IL-6) content and CB
      values, whereas higher levels of CB correlated with reduced serum IL-8 values and
      with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation.
      When CB was used to stimulate patients' PBLCs in vitro, the levels of IL-6 and
      tumour necrosis factor-alpha were increased. The data showed that bilirubin plays
      a role in STAT function and affects cytokine profile expression during HAV
      infection. 

PMID- 24943112
TI  - Correlates of neighborhood environment with walking among older Asian Americans.
AB  - OBJECTIVE: There is a limited research and understanding regarding the physical
      activity (PA) of older Asian Americans. This study examined the associations
      between neighborhood factors and walking among older Asian Americans. METHOD:
      Drawing from the 2003 California Health Interview Survey, our sample included
      1,045 older adults aged 55 and above representing five Asian groups: Chinese,
      Filipino, Japanese, Korean, and Vietnamese. Zero-inflated negative binomial
      regression models were used to test the association between neighborhood factors
      and walking. RESULTS: The results showed that different from the less active
      health profile among Asian Americans when compared with White adults, Asian older
      adults overall walked considerably more than White seniors. Higher neighborhood
      cohesion was associated with more walking among some groups but not all.
      Association between other neighborhood factors and walking varied among the
      ethnic groups. DISCUSSION: Health promotion policies and programs should be
      strategically tailored for specific ethnic groups to more effectively promote PA
      among older Asian Americans.

PMID- 24943115
TI  - North American animal breeding and production: meeting the needs of a changing
      landscape.

PMID- 24943113
TI  - Anaphylaxis caused by ingesting jellyfish in a subject with fermented soybean
      allergy: possibility of epicutaneous sensitization to poly-gamma-glutamic acid by
      jellyfish stings.

PMID- 24943116
TI  - Design of synthetic microbial communities for biotechnological production
      processes.
AB  - In their natural habitats microorganisms live in multi-species communities, in
      which the community members exhibit complex metabolic interactions. In contrast,
      biotechnological production processes catalyzed by microorganisms are usually
      carried out with single strains in pure cultures. A number of production
      processes, however, may be more efficiently catalyzed by the concerted action of
      microbial communities. This review will give an overview of organismic
      interactions between microbial cells and of biotechnological applications of
      microbial communities. It focuses on synthetic microbial communities that consist
      of microorganisms that have been genetically engineered. Design principles for
      such synthetic communities will be exemplified based on plausible scenarios for
      biotechnological production processes. These design principles comprise
      interspecific metabolic interactions via cross-feeding, regulation by
      interspecific signaling processes via metabolites and autoinducing signal
      molecules, and spatial structuring of synthetic microbial communities. In
      particular, the implementation of metabolic interdependencies, of positive
      feedback regulation and of inducible cell aggregation and biofilm formation will
      be outlined. Synthetic microbial communities constitute a viable extension of the
      biotechnological application of metabolically engineered single strains and
      enlarge the scope of microbial production processes. 

PMID- 24943117
TI  - Enhanced elimination of perfluorooctane sulfonic acid by menstruating women:
      evidence from population-based pharmacokinetic modeling.
AB  - Human biomonitoring studies have shown that concentrations of perfluorooctane
      sulfonic acid (PFOS) in men are higher than in women. We investigate sex
      differences in elimination of PFOS by fitting a population-based pharmacokinetic
      model to six cross-sectional data sets from 1999 to 2012 from the US National
      Health and Nutrition Examination Survey (NHANES) and derive human first-order
      elimination rate constants (kE) and corresponding elimination half-lives (t1/2)
      for PFOS, where t1/2 = ln 2/kE. We use a modified version of the Ritter
      population-based pharmacokinetic model and derive elimination rate constants
      separately for men and women. The model accounts for population-average lifetime
      changes in PFOS intake, body weight, and menstruation rate. We compare the model
      derived elimination rate constant for hypothetical nonmenstruating women to the
      elimination rate constant for men and women when menstruation is included as a
      loss process to evaluate the hypothesis that loss of PFOS by menstruation is an
      important process for women. The modeled elimination half-life for men is 4.7
      years, and the modeled elimination half-life for women when excluding losses from
      menstruation is 3.7 years. The elimination half-life for women when menstruation
      is included in the model is 4.0 years. Thus, menstruation accounts for 30% of the
      discrepancy in elimination of PFOS between men and women. The remaining
      discrepancy is likely due to other sex-specific elimination routes that are not
      considered in our modeling. 

PMID- 24943120
TI  - Clots and cardiac valve prostheses.

PMID- 24943118
TI  - Circomics of Cuban geminiviruses reveals the first alpha-satellite DNA in the
      Caribbean.
AB  - Circomics (circular DNA genomics), the combination of rolling circle
      amplification (RCA), restriction fragment length polymorphism (RFLP) analysis and
      pyro-sequencing, has been used recently to identify geminiviruses with high
      efficiency and low costs. Circular DNAs associated with Cuban geminiviruses were
      characterised by RCA/RFLP analysis and 454 sequencing of two batches of DNA
      amplified from selected plant samples as well as individual cloning and Sanger
      sequencing of DNA components and compared to other geminiviral DNAs by
      phylogenetic analysis. Cuban geminiviruses that were closely related to each
      other challenged the circomics approach. Ten geminiviral components and one alpha
      satellite DNA were determined and compared to three geminiviral components
      obtained by conventional cloning. New strains of Sida yellow mottle virus
      (SiYMoV), tomato yellow distortion leaf virus (ToYDLV), Sida golden mosaic
      Florida virus (SiGMFV) and Sida golden mosaic Liguanea virus (SiGMLV) are
      described with host plant species being classified by molecular PCR-based bar
      coding. A new virus species is named Peristrophe mosaic virus. The first alpha
      satellite found in Middle America establishes the New World branch of these
      elements which are related to nanoviruses and were previously thought to be
      restricted to the Old World. In conclusion, circomics is efficient for complex
      infections and closely related viruses to detected unexpected viral DNAs, but may
      need some scrutinisation by direct sequencing and cloning of individual
      components for certain cases. 

PMID- 24943121
TI  - An aggressive vertebral hemangioma in pregnancy: a case report.
AB  - INTRODUCTION: Pregnancy-related compressive myelopathy secondary to vertebral
      hemangioma is a rare occurrence and its treatment antepartum is rare. CASE
      PRESENTATION: A 19-year-old North African woman in her 38th week of pregnancy
      presented with paraplegia that progressed within 2 days after a rapidly
      progressive weakness of her lower limbs. Magnetic resonance imaging studies
      showed compression of her spinal cord in front of the fourth thoracic vertebra
      for suspected tuberculous spondylitis. A Caesarean section was done followed by
      corpectomy with a bone graft because we intraoperatively discovered a vertebral
      hemangioma. Pathology showed an aggressive hemangioma. CONCLUSION: At any term of
      pregnancy, extensive neurological involvement which is rapidly progressive due to
      compression should be considered for immediate decompression.

PMID- 24943122
TI  - A multiple-responsive self-healing supramolecular polymer gel network based on
      multiple orthogonal interactions.
AB  - Supramolecular polymer networks have attracted considerable attention not only
      due to their topological importance but also because they can show some fantastic
      properties such as stimuli-responsiveness and self-healing. Although various
      supramolecular networks are constructed by supramolecular chemists based on
      different non-covalent interactions, supramolecular polymer networks based on
      multiple orthogonal interactions are still rare. Here, a supramolecular polymer
      network is presented on the basis of the host-guest interactions between dibenzo
      24-crown-8 (DB24C8) and dibenzylammonium salts (DBAS), the metal-ligand
      coordination interactions between terpyridine and Zn(OTf)2 , and between 1,2,3
      triazole and PdCl2 (PhCN)2 . The topology of the networks can be easily tuned
      from monomer to main-chain supramolecular polymer and then to the supramolecular
      networks. This process is well studied by various characterization methods such
      as (1) H NMR, UV-vis, DOSY, viscosity, and rheological measurements. More
      importantly, a supramolecular gel is obtained at high concentrations of the
      supramolecular networks, which demonstrates both stimuli-responsiveness and self
      healing properties. 

PMID- 24943123
TI  - Addressing adolescent substance use in a paediatric health-care setting.
AB  - AIM: The aim of this study is to review the operation of a specialist adolescent
      drug and alcohol consultation liaison service in a tertiary paediatric hospital.
      METHOD: A retrospective review of patient records was conducted to identify
      patient characteristics and assess service utilisation. RESULTS: Two hundred
      adolescents were referred over 4 years. Most presented during mid-adolescence (14
      16 years). Alcohol, cannabis and nicotine were the most frequently reported
      substances, and almost half of referrals involved polysubstance use. Mental
      health diagnoses and behavioural problems were commonly reported. Almost two
      thirds (63.5%) attended an appointment for drug and alcohol assessment and
      intervention (n = 92) or were referred to appropriate services (n = 35).
      Adolescents more likely to engage and attend an appointment with the specialist
      adolescent addiction medicine service included those with amphetamine use,
      polysubstance use, chronic illness, any mental health diagnosis and mood
      disorder. Indigenous Australians and those with a history of aggression were more
      difficult to engage. CONCLUSIONS: Adolescents present to paediatric health
      settings with drug- and alcohol-related issues, including associated harms. These
      comprise, but are not limited to, physical and sexual assault, family conflict,
      mood and behavioural concerns (including psychosis), and forensic issues. Early
      intervention aims to reduce long-term risks such as dependence in adulthood.
      Specialist adolescent drug and alcohol services may assist in identifying and
      engaging these high-risk and often complex young people in developmentally
      appropriate treatment.

PMID- 24943124
TI  - Complete sucrose hydrolysis by heat-killed recombinant Pichia pastoris cells
      entrapped in calcium alginate.
AB  - BACKGROUND: An ideal immobilized biocatalyst for the industrial-scale production
      of invert sugar should stably operate at elevated temperatures (60-70 degrees C)
      and high sucrose concentrations (above 60%, w/v). Commercial invertase from the
      yeast Saccharomyces cerevisiae is thermolabile and suffers from substrate
      inhibition. Thermotoga maritima beta-fructosidase (BfrA) is the most thermoactive
      and thermostable sucrose-hydrolysing enzyme so far identified and allows complete
      inversion of the substrate in highly concentrated solutions. RESULTS: In this
      study, heat-killed Pichia pastoris cells bearing N-glycosylated BfrA in the
      periplasmic space were entrapped in calcium alginate beads. The immobilized
      recombinant yeast showed maximal sucrose hydrolysis at pH 5-7 and 90 degrees C.
      BfrA was 65% active at 60 degrees C and had no activity loss after incubation
      without the substrate at this temperature for 15 h. Complete inversion of cane
      sugar (2.04 M) at 60 degrees C was achieved in batchwise and continuous operation
      with respective productivities of 4.37 and 0.88 gram of substrate hydrolysed per
      gram of dry beads per hour. The half-life values of the biocatalyst were 14 and
      20 days when operated at 60 degrees C in the stirred tank and the fixed-bed
      column, respectively. The reaction with non-viable cells prevented the occurrence
      of sucrose fermentation and the formation of by-products. Six-month storage of
      the biocatalyst in 1.46 M sucrose (pH 5.5) at 4 degrees C caused no reduction of
      the invertase activity. CONCLUSIONS: The features of the novel thermostable
      biocatalyst developed in this study are more attractive than those of immobilized
      S. cerevisiae cells for application in the enzymatic manufacture of inverted
      sugar syrup in batch and fixed-bed reactors.

PMID- 24943125
TI  - Successful treatment of a rare case of neonatal Ebstein anomaly in a very low
      birth-weight premature neonate.
AB  - We report a successfully treated rare case of neonatal Ebstein anomaly in a low
      birth-weight infant.

PMID- 24943126
TI  - Relative motions between left flipper and dorsal fin domains favour P2X4 receptor
      activation.
AB  - Channel gating in response to extracellular ATP is a fundamental process for the
      physiological functions of P2X receptors. Here we identify coordinated allosteric
      changes in the left flipper (LF) and dorsal fin (DF) domains that couple ATP
      binding to channel gating. Engineered disulphide crosslinking or zinc bridges
      between the LF and DF domains that constrain their relative motions significantly
      influence channel gating of P2X4 receptors, confirming the essential role of
      these allosteric changes. ATP-binding-induced alterations in interdomain
      hydrophobic interactions among I208, L217, V291 and the aliphatic chain of K193
      correlate well with these coordinated relative movements. Mutations on those four
      residues lead to impaired or fully abolished channel activations of P2X4
      receptors. Our data reveal that ATP-binding-induced altered interdomain
      hydrophobic interactions and the concomitant coordinated motions of LF and DF
      domains are allosteric events essential for the channel gating of P2X4 receptors.

PMID- 24943127
TI  - Melanocortin 4 receptor activation inhibits presynaptic N-type calcium channels
      in amygdaloid complex neurons.
AB  - The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor involved in
      food intake and energy expenditure regulation. MC4R activation modifies neuronal
      activity but the molecular mechanisms by which this regulation occurs remain
      unclear. Here, we tested the hypothesis that MC4R activation regulates the
      activity of voltage-gated calcium channels and, as a consequence, synaptic
      activity. We also tested whether the proposed effect occurs in the amygdala, a
      brain area known to mediate the anorexigenic actions of MC4R signaling. Using the
      patch-clamp technique, we found that the activation of MC4R with its agonist
      melanotan II specifically inhibited 34.5 +/- 1.5% of N-type calcium currents in
      transiently transfected HEK293 cells. This inhibition was concentration
      dependent, voltage-independent and occluded by the Galphas pathway inhibitor
      cholera toxin. Moreover, we found that melanotan II specifically inhibited 25.9
      +/- 2.0% of native N-type calcium currents and 55.4 +/- 14.4% of evoked
      inhibitory postsynaptic currents in mouse cultured amygdala neurons. In vivo, we
      found that the MC4R agonist RO27-3225 increased the marker of cellular activity c
      Fos in several components of the amygdala, whereas the N-type channel blocker
      omega conotoxin GVIA increased c-Fos expression exclusively in the central
      subdivision of the amygdala. Thus, MC4R specifically inhibited the presynaptic N
      type channel subtype, and this inhibition may be important for the effects of
      melanocortin in the central subdivision of the amygdala.

PMID- 24943128
TI  - Detecting disease outbreaks in mass gatherings using Internet data.
AB  - BACKGROUND: Mass gatherings, such as music festivals and religious events, pose a
      health care challenge because of the risk of transmission of communicable
      diseases. This is exacerbated by the fact that participants disperse soon after
      the gathering, potentially spreading disease within their communities. The
      dispersion of participants also poses a challenge for traditional surveillance
      methods. The ubiquitous use of the Internet may enable the detection of disease
      outbreaks through analysis of data generated by users during events and shortly
      thereafter. OBJECTIVE: The intent of the study was to develop algorithms that can
      alert to possible outbreaks of communicable diseases from Internet data,
      specifically Twitter and search engine queries. METHODS: We extracted all Twitter
      postings and queries made to the Bing search engine by users who repeatedly
      mentioned one of nine major music festivals held in the United Kingdom and one
      religious event (the Hajj in Mecca) during 2012, for a period of 30 days and
      after each festival. We analyzed these data using three methods, two of which
      compared words associated with disease symptoms before and after the time of the
      festival, and one that compared the frequency of these words with those of other
      users in the United Kingdom in the days following the festivals. RESULTS: The
      data comprised, on average, 7.5 million tweets made by 12,163 users, and 32,143
      queries made by 1756 users from each festival. Our methods indicated the
      statistically significant appearance of a disease symptom in two of the nine
      festivals. For example, cough was detected at higher than expected levels
      following the Wakestock festival. Statistically significant agreement (chi-square
      test, P<.01) between methods and across data sources was found where a
      statistically significant symptom was detected. Anecdotal evidence suggests that
      symptoms detected are indeed indicative of a disease that some users attributed
      to being at the festival. CONCLUSIONS: Our work shows the feasibility of creating
      a public health surveillance system for mass gatherings based on Internet data.
      The use of multiple data sources and analysis methods was found to be
      advantageous for rejecting false positives. Further studies are required in order
      to validate our findings with data from public health authorities.

PMID- 24943129
TI  - Vancomycin versus daptomycin for the treatment of methicillin-resistant
      Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum
      inhibitory concentrations: study protocol for a phase IIB randomized controlled
      trial.
AB  - BACKGROUND: Vancomycin is the standard first-line treatment for methicillin
      resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines
      recommend that clinicians consider using alternative agents such as daptomycin
      when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To
      date however, there have been no head-to-head randomized trials comparing the
      safety and efficacy of daptomycin and vancomycin in the treatment of such
      infections. The primary aim of our study is to compare the efficacy of daptomycin
      versus vancomycin in the treatment of bloodstream infections due to methicillin
      resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory
      concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all
      cause 60-day mortality. METHODS/DESIGN: The study is designed as a multicenter
      prospective open label phase IIB pilot randomized controlled trial. Eligible
      participants will be inpatients over 21-years-old with a positive blood culture
      for methicillin-resistant Staphylococcus aureus with vancomycin minimum
      inhibitory concentration of greater than or equal to 1.5 ug/ml. Randomization
      into intervention or active control arms will be performed with a 1:1 allocation
      ratio. We aim to recruit 50 participants over a period of two years. Participants
      randomized to the active control arm will receive vancomycin dose-while those
      randomized to the intervention arm will receive daptomycin. Participants will
      receive a minimum of 14 days study treatment.The primary analysis will be
      conducted on the intention-to-treat principle. The Fisher's exact test will be
      used to compare the 60-day mortality rate from index blood cultures (primary
      endpoint) between the two treatment arms, and the exact two-sided 95% confidence
      interval will be calculated using the Clopper and Pearson method. Primary
      analysis will be conducted using a two sided alpha of 0.05. DISCUSSION: If
      results from this pilot study suggest that daptomycin shows significant efficacy
      in the treatment of bloodstream infections due to methicillin-resistant
      Staphylococcus aureus isolates with high vancomycin minimum inhibitory
      concentrations, we aim to proceed with a larger scale confirmatory study. This
      would help guide clinicians and inform practice guidelines on the optimal
      treatment for such infections. TRIAL REGISTRATION: The trial is listed on
      clinicaltrials.gov (NCT01975662, date of registration: 29 October 2013).

PMID- 24943130
TI  - Anatomical Parts-Based Regression Using Non-Negative Matrix Factorization.
AB  - Non-negative matrix factorization (NMF) is an excellent tool for unsupervised
      parts-based learning, but proves to be ineffective when parts of a whole follow a
      specific pattern. Analyzing such local changes is particularly important when
      studying anatomical transformations. We propose a supervised method that
      incorporates a regression constraint into the NMF framework and learns maximally
      changing parts in the basis images, called Regression based NMF (RNMF). The
      algorithm is made robust against outliers by learning the distribution of the
      input manifold space, where the data resides. One of our main goals is to achieve
      good region localization. By incorporating a gradient smoothing and independence
      constraint into the factorized bases, contiguous local regions are captured. We
      apply our technique to a synthetic dataset and structural MRI brain images of
      subjects with varying ages. RNMF finds the localized regions which are expected
      to be highly changing over age to be manifested in its significant basis and it
      also achieves the best performance compared to other statistical regression and
      dimensionality reduction techniques.

PMID- 24943131
TI  - A pilot study to evaluate renal hemodynamics in cirrhosis by simultaneous
      glomerular filtration rate, renal plasma flow, renal resistive indices and
      biomarkers measurements.
AB  - BACKGROUND: Renal hemodynamic measurements are complicated to perform in patients
      with cirrhosis, yet they provide the best measure of risk to predict hepatorenal
      syndrome (HRS). Currently, there are no established biomarkers of altered renal
      hemodynamics in cirrhosis validated by measured renal hemodynamics. METHODS: In
      this pilot study, simultaneous measurements of glomerular filtration rate (GFR),
      renal plasma flow (RPF), renal resistive indices and biomarkers were performed to
      evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients
      without ascites, 5 with diuretic-sensitive and 2 diuretic-refractory ascites).
      RESULTS: Patients with diuretic-refractory ascites had the lowest mean GFR (36.5
      ml/min/1.73 m(2)) and RPF (133.6 ml/min/1.73 m(2)) when compared to those without
      ascites (GFR 82.9 ml/min/1.73 m(2), RPF 229.9 ml/min/1.73 m(2)) and with diuretic
      sensitive ascites (GFR 82.3 ml/min/1.73 m(2), RPF 344.1 ml/min/1.73 m(2)). A
      higher mean filtration fraction (FF) (GFR/RPF 0.36) was noted among those without
      ascites compared to those with ascites. Higher FF in patients without ascites is
      most likely secondary to the vasoconstriction in the efferent glomerular
      arterioles (normal FF ~0.20). In general, renal resistive indices were inversely
      related to FF. While patients with ascites had lower FF and higher right kidney
      main and arcuate artery resistive indices, those without ascites had higher FF
      and lower right kidney main and arcuate artery resistive indices. While cystatin
      C and beta2-microglobulin performed better compared to Cr in estimating RPF, beta
      trace protein, beta2-microglobulin, and SDMA, and (SDMA+ADMA) performed better in
      estimating right kidney arcuate artery resistive index. CONCLUSION: The results
      of this pilot study showed that identification of non-invasive biomarkers of
      reduced RPF and increased renal resistive indices can identify cirrhotics at risk
      for HRS at a stage more amenable to therapeutic intervention and reduce mortality
      from kidney failure in cirrhosis.

PMID- 24943133
TI  - Loss of cerebral white matter in primary Sjogren's syndrome: a controlled
      volumetric magnetic resonance imaging study.
AB  - BACKGROUND AND PURPOSE: Although brain involvement is common in primary Sjogren's
      syndrome (pSS), results from cerebral imaging studies are inconsistent. This
      study aimed to perform both voxel-wise and global brain volume analyses in a
      nearly population-based pSS cohort to explore whether the patients displayed any
      focal or diffuse volume differences compared with healthy subjects. METHODS:
      Global grey matter (GM) and white matter (WM) volumes were measured and compared
      in 60 patients with pSS and 60 age- and gender-matched healthy subjects.
      Regression models were constructed with potential explanatory variables for GM
      and WM volumes. In the same groups, voxel-wise morphometric analyses were
      performed. RESULTS: In analyses of global GM and WM, the patients had lower WM
      volumes than healthy subjects (540 +/- 63 cm(3) vs. 564 +/- 56 cm(3), P = 0.02),
      but no differences in GM. Voxel-wise analyses displayed no localized areas of GM
      or WM volume differences between pSS patients and healthy subjects. CONCLUSION:
      Individuals with pSS have a diffuse reduction of cerebral WM but no localized
      loss of WM or GM. This indicates a general deleterious effect on WM due to pSS
      itself.

PMID- 24943132
TI  - Predicting the size of unerupted canines and premolars using primary maxillary
      first molar.
AB  - AIM: One of the most important aspects of interceptive orthodontic diagnosis and
      treatment planning is space analysis. To date all methods use the size of
      permanent teeth to predict the dimensions of unerupted teeth. The aim of this
      study was to predict the permanent teeth size using maxillary primary first
      molar. METHODS: The size of primary maxillary first molars and permanent canines
      and premolars of 80 subjects was measured on their dental casts. Regression
      equations were determined between the size of primary maxillary first molars and
      permanent canines and premolars. RESULTS: The new regression equations for
      predicting permanent tooth size in the maxilla and mandible were, respectively, Y
      = 2.2X + 13 and Y = 2.4X + 9.5 among females and Y = 2.7X + 5.5 and Y = 2.4X +
      9.5 among males. CONCLUSIONS: The results show that the primary maxillary first
      molar size can be used to predict the size of unerupted permanent teeth.

PMID- 24943134
TI  - Unmasked Brugada pattern by ajmaline challenge in patients with myotonic
      dystrophy type 1.
AB  - BACKGROUND: Myotonic dystrophy type 1 (DM1) generates missplicing of the SCN5A
      gene, encoding the cardiac sodium channel (Nav 1.5). Brugada syndrome, which
      partly results from Nav 1.5 dysfunction and causes increased VF occurrence, can
      be unmasked by ajmaline. We aimed to investigate the response to ajmaline
      challenge in DM1 patients and its potential impact on their sudden cardiac death
      risk stratification. METHODS: Among 36 adult DM1 patients referred to our
      institution, electrophysiological study and ajmaline challenge were performed in
      12 patients fulfilling the following criteria: (1) PR interval >200 ms or QRS
      duration >100 ms; (2) absence of complete left bundle branch block; (3) absence
      of permanent ventricular pacing; (4) absence of implantable cardioverter
      defibrillator (ICD); (5) preserved left-ventricular ejection fraction >50%; and
      (6) absence of severe muscular impairment. Of note, DM1 patients with ajmaline
      induced Brugada pattern (BrP) were screened for SCN5A. RESULTS: In all the 12
      patients studied, the HV interval was <70 ms. A BrP was unmasked in three
      patients but none carried an SCN5A mutation. Ajmaline-induced sustained
      ventricular tachycardia occurred in one patient with BrP, who finally received an
      ICD. The other patients did not present any cardiac event during the entire
      follow-up (15 +/- 4 months). CONCLUSION: Our study is the first to describe a
      high prevalence of ajmaline-induced BrP in DM1 patients. The indications, the
      safety, and the implications of ajmaline challenge in this particular setting
      need to be determined by larger prospective studies.

PMID- 24943135
TI  - Utility of non-contrast-enhanced CT for improved detection of arterial phase
      hyperenhancement in hepatocellular carcinoma.
AB  - PURPOSE: To determine the utility of non-contrast-enhanced CT (NC-CT) for
      improved detection of hyperenhancement in hepatocellular carcinomas (HCC).
      METHODS: We performed a retrospective analysis on CT studies of 104 consecutive
      patients with 124 HCCs between October 2006 and December 2012. The enhancement of
      HCC was evaluated on quadriphasic CT: non-contrast (NC), arterial phase (AP),
      portal-venous phase (PVP), and delayed phases (DP) were performed. For
      determination of enhancement, mean attenuation of the HCC and surrounding non
      tumor bearing liver in the four phases were recorded. Hyperenhancement was
      defined by either HCC (AP-NC) representing absolute lesion enhancement or AP (HCC
      liver), representing relative enhancement. An increase of >=10 Hounsfield units
      (HU) was considered as enhancement. Two radiologists (R1 and R2) independently
      performed a conventional qualitative assessment for hyperenhancement of HCC. The
      accuracy of detection by proposed absolute lesion enhancement HCC (AP-NC) was
      compared to relative enhancement AP (HCC-liver) and qualitative assessment by
      readers with the McNemar test. RESULTS: The proposed criteria of absolute lesion
      enhancement, HCC (AP-NC) identified more hypervascular nodules compared to
      qualitative analysis (92% vs. 62% for R1 and 69% for R2), equating to an
      improvement of 23%-31%. In contrast, relative enhancement AP (HCC-liver) was
      found to be inferior to conventional qualitative analysis (50% vs. 62%-69% for
      readers). CONCLUSION: NC-CT is useful to improve the detection of
      hyperenhancement in HCCs for imaging diagnosis.

PMID- 24943137
TI  - Accessory spleen torsion in a teenager.

PMID- 24943136
TI  - Prospective evaluation of prior image constrained compressed sensing (PICCS)
      algorithm in abdominal CT: a comparison of reduced dose with standard dose
      imaging.
AB  - PURPOSE: To prospectively study CT dose reduction using the "prior image
      constrained compressed sensing" (PICCS) reconstruction technique. METHODS:
      Immediately following routine standard dose (SD) abdominal MDCT, 50 patients
      (mean age, 57.7 years; mean BMI, 28.8) underwent a second reduced dose (RD) scan
      (targeted dose reduction, 70%-90%). DLP, CTDIvol, and SSDE were compared. Several
      reconstruction algorithms (FBP, ASIR, and PICCS) were applied to the RD series.
      SD images with FBP served as reference standard. Two blinded readers evaluated
      each series for subjective image quality and focal lesion detection. RESULTS:
      Mean DLP, CTDIvol, and SSDE for RD series were 140.3 mGy cm (median 79.4), 3.7
      mGy (median 1.8), and 4.2 mGy (median 2.3) compared with 493.7 mGy cm (median
      345.8), 12.9 mGy (median 7.9 mGy), and 14.6 mGy (median 10.1) for SD series,
      respectively. Mean effective patient diameter was 30.1 cm (median 30), which
      translates to a mean SSDE reduction of 72% (P < 0.001). RD-PICCS image quality
      score was 2.8 +/- 0.5, improved over the RD-FBP (1.7 +/- 0.7) and RD-ASIR (1.9 +/
      0.8) (P < 0.001), but lower than SD (3.5 +/- 0.5) (P < 0.001). Readers detected
      81% (184/228) of focal lesions on RD-PICCS series, vs. 67% (153/228) and 65%
      (149/228) for RD-FBP and RD-ASIR, respectively. Mean image noise was
      significantly reduced on RD-PICCS series (13.9 HU) compared with RD-FBP (57.2)
      and RD-ASIR (44.1) (P < 0.001). CONCLUSION: PICCS allows for marked dose
      reduction at abdominal CT with improved image quality and diagnostic performance
      over reduced dose FBP and ASIR. Further study is needed to determine indication
      specific dose reduction levels that preserve acceptable diagnostic accuracy
      relative to higher dose protocols.

PMID- 24943139
TI  - Haemorrhage, hyponatraemia and more than just a hack.
AB  - A 43-year-old previously healthy solicitor presented with a 9-day history of
      cough productive of yellow sputum with a prodrome of sore throat and myalgia. The
      cough was paroxysmal in nature and severe enough to cause extensive bilateral
      subconjunctival haemorrhages and cough syncopes multiple times a day, with one
      bout of associated haematemesis on the day of admission. He was isolated, treated
      for a presumed atypical chest infection with tazocin and clarithromycin, and
      monitored carefully until the hyponatraemia on presentation was resolved.
      Atypical screen and blood cultures were sent off, though unexciting at first,
      eventually confirmed the unlikely; Bordetella pertussis, much to the surprise of
      many who had Legionella as the top differential. 

PMID- 24943140
TI  - Widespread surgical emphysema following trivial injury to the hand.
AB  - A 23-year-old glazer presented to the A&E department with pain in his left arm
      following a 2 mm puncture injury to his left thenar eminence. Examination showed
      crepitus throughout the arm and over the chest wall. Plain X-rays confirmed
      extensive surgical emphysema but no evidence of pneumothorax. Clinical
      observations and laboratory markers for infection were normal. The patient was
      prescribed broad spectrum antibiotics for presumed gas-producing organism
      infection. After 24 h cultures returned negative and no other signs of infection
      were detected. Treatment was discontinued and the patient was allowed home.
      Several days later he experienced severe diarrhoea and as a result required time
      off work. No cause was found on investigation. We postulate a benign aetiology
      for the surgical emphysema in this case. In future it may be possible to
      recognise benign surgical emphysema at presentation and avoid prescribing
      unnecessary antibiotics. 

PMID- 24943141
TI  - Pellagra in a patient with primary Sjogren's syndrome.
AB  - A 27-year-old woman presented with persistent dryness of the mouth and eyes. She
      presented with permanent photodistributed rash involving the face and distal
      extremities. Laboratory tests showed positive Sjogren's syndrome (SS)-A and SS-B
      antibodies. Histological examination of minor salivary gland biopsy revealed
      inflammatory infiltration grade 4 according to Chisholm's classification. Skin
      biopsy showed acanthosis, hyperkeratosis in the epidermis and little inflammatory
      infiltrate in the dermis. There was an infiltration of CD4 T lymphocytes in the
      dermis. Based on the characteristics of the dermatitis and on a rapid response to
      niacin replacement, the diagnosis of pellagra was carried out. A complete
      resolution of the dermatological signs was obtained within 2 months. To the best
      of our knowledge, the association between primary SS and pellagra has never been
      reported. We emphasise the possible mechanisms of this association. 

PMID- 24943138
TI  - Bigger data, collaborative tools and the future of predictive drug discovery.
AB  - Over the past decade we have seen a growth in the provision of chemistry data and
      cheminformatics tools as either free websites or software as a service commercial
      offerings. These have transformed how we find molecule-related data and use such
      tools in our research. There have also been efforts to improve collaboration
      between researchers either openly or through secure transactions using commercial
      tools. A major challenge in the future will be how such databases and software
      approaches handle larger amounts of data as it accumulates from high throughput
      screening and enables the user to draw insights, enable predictions and move
      projects forward. We now discuss how information from some drug discovery
      datasets can be made more accessible and how privacy of data should not overwhelm
      the desire to share it at an appropriate time with collaborators. We also discuss
      additional software tools that could be made available and provide our thoughts
      on the future of predictive drug discovery in this age of big data. We use some
      examples from our own research on neglected diseases, collaborations, mobile apps
      and algorithm development to illustrate these ideas. 

PMID- 24943142
TI  - Rhodococcus equi pneumonia and sepsis in an allogeneic haematopoietic stem cell
      transplant recipient.
AB  - Rhodococcus equi is an aerobic facultative intracellular organism that is known
      to infect cells of the macrophage-monocyte lineage. It is a common veterinary
      pathogen; however, the incidence of this infection in humans has risen and it has
      been recognised as an emerging opportunistic pathogen among the immunocompromised
      patients. We present the case of a patient with chronic myeloid leukaemia who had
      received allogenic stem cell transplant and presented to the hospital with
      clinical picture of pneumonia. Her condition worsened on initial broad spectrum
      antimicrobials and 3 weeks into her hospitalisation, R. equi was isolated from
      her broncheoalveolar lavage and blood cultures. Based on the susceptibility,
      therapy was changed to four active antimicrobials; however, the patient failed to
      improve and eventually died. This case highlights the importance of considering
      the diagnosis of R. equi among immunosuppressed patients early in the right
      clinical setting due to the high virulence associated with this organism. 

PMID- 24943143
TI  - Are we missing anaerobic infective endocarditis in some acute coronary syndromes?
AB  - A 76-year-old man presented with a 3-week history of intermittent fevers and
      dyspnoea on exertion after a dental bridge placement 2 months ago. The patient's
      medical history was significant for mild to moderate mitral valve prolapse.
      Initial evaluation was notable for a 3/6 systolic apical murmur. Laboratory
      investigations revealed leucocytosis and elevated erythrocyte sedimentation rate,
      C reactive protein and cardiac biomarkers. Patient was treated initially for non
      ST elevation myocardial infarction. A 2-dimensional echocardiography was
      concerning for a new mitral regurgitation and a questionable vegetation adjacent
      to the mitral valve annulus. Transoesophageal echocardiography study confirmed
      the diagnosis. Subsequent microbial identification was notable for
      Peptostreptococci and he was started on intravenous penicillin therapy. The
      unexplained illness with underlying valve disease prompted consideration of
      infective endocarditis. This case describes a rare occurrence of anaerobic
      endocarditis imitating an acute coronary event.

PMID- 24943144
TI  - Phantom tumour of the lung in a patient with renal failure misdiagnosed as chest
      infection.
AB  - Phantom or vanishing tumour of the lung is a rare finding on chest radiographs
      that has been reported secondary to heart failure or chronic kidney disease. It
      has been described as an interlobular effusion of the transverse or oblique
      fissure of the right lung. Although it is uncommon, it should always be
      considered as a differential diagnosis for a radiographic opacity of the right
      middle lung zone because it can be easily mistaken for a lung mass or
      infiltration. We herein present a case involving a patient with chronic kidney
      disease and a radiographic opacity of the right-middle lung that was diagnosed as
      a chest infection. The patient did not respond to various antibiotics and showed
      a poor response to diuretics, the standard treatment for phantom tumour. However,
      the patient markedly improved after dialysis, and the radiographic chest opacity
      disappeared. 

PMID- 24943145
TI  - Hand and wrist.

PMID- 24943146
TI  - Redescription of immatures and bionomy of the Palaearctic species dicladispa
      testacea (Linnaeus, 1767) (Coleoptera: Chrysomelidae: Cassidinae: Hispini), a
      leaf-mining hispine beetle.
AB  - Dicladispa testacea (Linnaeus, 1767) is a member of the tribe Hispini Gyllenhal,
      1813 associated with plants of the family Cistaceae Juss. and is widely
      distributed in the Mediterranean Basin. Immature stages are described in detail,
      including line drawings, chaetotaxy, sculpture of integument, and SEM photos of
      morphological details. This is the first detailed description of immatures in the
      tribe Hispini, and this can be regarded as a model description for studies of
      other species in the tribe. Diagnostic characters for this species in comparison
      with other described larvae and pupae of the genus Dicladispa and the sympatric
      Hispa atra Linnaeus, 1767 are discussed. Some remarks on the biology of
      Dicladispa testacea, such as host plants, feeding patterns of adults, structure
      of larval and pupal mines, are also given. 

PMID- 24943147
TI  - A new genus and species of Platyischnopidae (Amphipoda: Gammaridea) from the
      Argentine sea, South-West Atlantic ocean.
AB  - The family Platyischnopidae is herein reported for the first time in the
      Argentine Sea, South-West Atlantic Ocean. A new genus and species, Platyisao
      holodividum gen. et. sp. nov., collected off the coast of Buenos Aires and Rio
      Negro provinces, is fully described and illustrated. Platyisao gen. nov. is
      distinguished from the eight other genera of Platyischnopidae by the gnathopods
      subchelate, and the telson elongate, completely cleft. In addition, the
      distribution of Tiburonella viscana (Barnard J.L., 1964), up to now known in the
      South-West Atlantic Ocean from Brazilian waters, is extended to the coast off
      Buenos Aires province, Argentina. 

PMID- 24943148
TI  - Checklist of Vietnamese Orthoptera (Saltatoria).
AB  - This study presents all known Vietnamese Orthoptera (Saltatoria) from 1887 to
      2013 as a summarized checklist that includes currently valid names and synonyms
      for the fauna with their type localities. The sources are compared with reliable
      references and Orthoptera species file online. A total of 656 species and 12
      families were estimated to occur in Vietnam through present. 

PMID- 24943149
TI  - The strange case of Laetesia raveni n. sp., a green linyphiid spider from Eastern
      Australia with a preference for thorny plants (Araneae, Linyphiidae).
AB  - Laetesia raveni n. sp. (Araneae, Linyphiidae), is described based on specimens
      collected in New South Wales and Queensland (Australia). This new linyphiid
      species is of bright green colour, and it seems to have a preference to build its
      webs almost exclusively on two plant species, namely Calamus muelleri Wendland
      (Arecaceae) and Solanum inaequilaterum Domin, (Solanaceae), both of them densely
      covered with thorns. The epigynal morphology of Laetesia raveni n. sp. varies
      intraspecifically. Live individuals and several of their dome-shaped sheet webs
      are illustrated.  

PMID- 24943150
TI  - Third instar of the myrmecophilous Italochrysa insignis (Walker) from Australia
      (Neuroptera: Chrysopidae: Belonopterygini).
AB  - The third instar of the Australian green lacewing Italochrysa insignis (Walker)
      is described and compared with that of the European Italochrysa italica (Rossi).
      Larvae of both species are associated with arboreal ant nests. Moreover, they
      share a substantial number of morphological adaptations that may defend them
      against ants and that distinguish them from larvae of other chrysopids. The
      larvae of the two Italochrysa Principi species also have distinct differences.
      The potential systematic value of several of the larval characters at the tribal,
      generic, and species levels is assessed, and a brief review of myrmecophily in
      the Belonopterygini is presented. 

PMID- 24943151
TI  - A new species of Corydalus Latreille, 1802 (Megaloptera, Corydalidae) and first
      record of C. clavijoi Contreras-Ramos, 2002 and C. Nubilus Erichson, 1848 from
      Colombia.
AB  - A new species of the dobsonfly genus Corydalus from the Colombian Andean region
      is described and illustrated. This species is unique in having the longest tenth
      gonostyli of all known species of the genus and is apparently closely related to
      members of the C. nubilus group. In addition, C. clavijoi Contreras-Ramos and C.
      nubilus Erichson are recorded for the first time from Colombia and new Colombian
      locality records are provided for other known species. A key to Colombian species
      of Corydalus is included. 

PMID- 24943152
TI  - On the colour types in Lycodes nakamurae (Tanaka, 1914) and species composition
      of the subgenus Furcimanus (Perciformes: Zoarcidae: Lycodes) in the sea of Japan.
AB  - Two colour types were revealed in a zoarcid fish of the subgenus Furcimanus,
      genus Lycodes, in the Sea of Japan. A comparison of morphometric, meristic and
      genetic characters in dark coloured and light coloured individuals suggests that
      the two colour morphs represent a single species, determined to be Lycodes
      nakamurae (Tanaka, 1914). Variability in colouration within L. nakamurae and a
      lack of morphological or molecular characters distinguishing L. nakamurae from L.
      nishimurai Shinohara & Shirai, 2005 suggest that the latter should be considered
      a synonym of L. nakamurae (Tanaka, 1914). A record of L. pectoralis in the waters
      of the Republic of Korea is regarded as a misidentification. Thus, we conclude
      that only one species of the Lycodes subgenus Furcimanus, L. nakamurae, with dark
      and light colour morphs as well as specimens of intermediate colouration,
      inhabits the Sea of Japan. 

PMID- 24943153
TI  - Description of a new species of rabbitfish (Perciformes: Siganidae) from southern
      India, Sri Lanka and the Maldives.
AB  - Siganus insomnis sp. nov. is described from the Maldives, Sri Lanka and southern
      India. It most closely resembles S. lineatus (Valenciennes) from the Western
      Pacific but differs in coloration, principally in that most if not all of the
      bronze bands on its mid and upper sides continue horizontally and unbroken
      through to the nape and opercular slit. By contrast, in S. lineatus, typically
      the anterior area below the spinous dorsal fin down to the mid-sides is
      irregularly marked with golden bronze spots, commas, or a maze of contorted
      lines. S. guttatus (Bloch) is the third member of this group of sibling species;
      its sides are covered with orange to bronze-gold spots. It is distributed
      throughout S.E. Asia, i.e., it occupies a geographic position between the areas
      inhabited by S. lineatus and S. insomnis. Thus the gene pools of S. lineatus and
      S. insomnis are quarantined from one another by distance and the intervening
      presence of S. guttatus in S.E. Asia. The geographical separation of the
      populations of S. lineatus and S. insomnis from one another is reinforced by the
      absence of suitable, coralline habitats for these species in the western half of
      the Bay of Bengal.  

PMID- 24943154
TI  - Review of the cicada genus Platylomia Stal (Hemiptera, Cicadidae) from China,
      with description and bioacoustics of a new species from Mts. Qinling.
AB  - The species of Platylomia Stal from China are reviewed and a new species, P.
      shaanxiensis sp. n., from Shaanxi, China is described. Acoustic signals produced
      by males of this new species were recorded and analyzed. P. juno Distant is
      transferred to the genus Macrosemia. A key to the species of Platylomia from
      China is provided. 

PMID- 24943155
TI  - Systematic relationships of Vuilletia and Senegathrips (Thysanoptera,
      Phlaeothripinae) from galls on the West African shrub Guiera senegalensis.
AB  - Widespread and common across much of the drier areas of western Africa, the woody
      shrub Guiera senegalensis (Combretaceae) is the sole member of its genus.
      Similarly widespread is Vuilletia houardi, a thrips species that induces galls on
      this shrub, and is recorded from Mali, Senegal, Gambia and northern Nigeria
      (Pitkin & Mound 1973). Moreover, large numbers of galls, together with their
      included thrips, have now been studied from Burkina Faso. Some galls (Figs 1, 2)
      are invaded by Senegathrips coutini, a species whose biology is not known but
      that is possibly a predator. Moreover, Liothrips africana also sometimes breeds
      within these galls, but is possibly using these only as a convenient shelter. A
      re-description and line-drawings of V. houardi was provided by zur Strassen
      (1958), but no modern diagnosis of this genus, nor of Senegathrips, is available,
      the objective here being to provide formal diagnoses for these two monotypic
      genera.  

PMID- 24943156
TI  - Replacement names for Eutrigaster (Graffia) Csuzdi & Zicsi, 1991 and Dichogaster
      (Malawia) Csuzdi, 2010 (Oligochaeta, Acanthodrilidae).
AB  - The earthworm genus Eutrigaster Cognetti, 1904 has long been in synonymy with
      Dichogaster Beddard, 1888 until Sims (1987) resurrected it for the Central
      American Dichogaster-like species possessing a muscular proventriculus in segment
      5. Today the genus consists of some 50 species distributed in two subgenera
      (Csuzdi 2012). The subgenus Eutrigaster (Graffia) Csuzdi & Zicsi, 1991 was
      erected for species that differ from the type species of the genus in possessing
      penial setae. According to the summary by Fragoso & Brown (2007) the subgenus
      Graffia contained 27 taxa. Later, further three species were described (Sherlock
      et al. 2011; Sherlock & Csuzdi 2013). However, the subgenus name Graffia is a
      junior homonym of the turbellarian genus Graffia Levinsen, 1879. (A further
      junior homonym Graffia Ihering, 1880 (Platyhelminthes: Turbellaria) has already
      been renamed as Graffilla Ihering, 1880). Here the replacement name Eutrigaster
      (Graffiona) nom. nov. is proposed for the earthworm subgenus Eutrigaster
      (Graffia). 

PMID- 24943158
TI  - The Paranthrenini of mainland China (Lepidoptera, Sesiidae).
AB  - We here briefly review the Paranthrenini fauna of Mainland China and provide a
      checklist of 21 species for this region. We describe six new species: Paranthrene
      rubomacula Kallies & Owada sp. nov., Nokona opaca Kallies & Wang sp. nov., Nokona
      bractea Kallies & Arita sp. nov., Scoliokona nanlingensis Kallies & Arita sp.
      nov., Scoliokona spissa Kallies & Arita sp. nov., Scoliokona shimentai Kallies &
      Wu sp. nov. Furthermore, we provide numerous new combinations of species formerly
      associated with the genus Paranthrene in South East Asia, with 12 species
      transferred to Nokona Matsumura, 1931, 4 to Scoliokona Kallies & Arita, 1998, and
      one to Cyanosesia Gorbunov & Arita, 1995 (comb. nov.). The genus name Aritasesia
      Nakamura, 2009 (syn. nov.) is considered a junior subjective synonym of Nokona
      Matsumura, 1931.  

PMID- 24943157
TI  - Insects found in birds' nests from Argentina: Coryphistera alaudina Burmeister,
      1860 (Aves: Furnariidae), their inquiline birds and mammals, new hosts for
      Psammolestes coreodes Bergroth, 1911 and Triatoma platensis Neiva, 1913
      (Hemiptera: Reduviidae: Triatominae).
AB  - The insect fauna in nests of Coryphistera alaudina Burmeister, 1860 (Aves:
      Furnariidae) were studied in the provinces of Santiago del Estero, Chaco,
      Cordoba, and La Pampa in Argentina. A total of 7364 insect specimens comprising
      77 taxa in a total of 29 families and 7 orders was found in their nests: 40
      identified to species, 23 identified to genus, and 14 identified to family.
      Coryphistera alaudina and some of their vertebrate inquilines are new host
      records for the triatomine bugs Psammolestes coreodes Bergroth, 1911 and/or
      Triatoma platensis Neiva, 1913 (Hemiptera: Reduviidae). The insects in the nests
      of C. alaudina are separated by functional guilds, and their permanence time
      inside the nests are presented in a new manner and discussed. 

PMID- 24943159
TI  - A new species of swamp rat of the genus Scapteromys waterhouse, 1837 (Rodentia:
      Sigmodontinae) endemic to Araucaria angustifolia forest in Southern Brazil.
AB  - A new species of swamp rat of the genus Scapteromys from the Meridional Plateau
      of Southern Brazil is described. Morphological, molecular, and karyological
      analysis support the recognition of the new species, distinct from S. aquaticus
      and S. tumidus. Scapteromys sp. nov. is significantly smaller than the congeneric
      taxa considering most of the external and craniometric measurements and the
      pelage is conspicuously grayer and darker. It can be distinguished from S.
      tumidus by the laterally extended thenar pad of the manus and the parallel edges
      of the hamular process of the pterygoid, and from S. aquaticus by a grayer and
      darker pelage and smaller values of most external and craniometric measurements.
      Karyological analysis indicated a difference in chromosome numbers across the
      distributional range: 2n=34 and 2n=36. A total of 11 haplotypes were found along
      the range of the new species within the biogeographic province of Araucaria
      angustifolia Forest. Strongly supported substructure was found within the new
      taxon, resulting in two reciprocally monophyletic clades. 

PMID- 24943160
TI  - The unique Brazilian species of Polylobus Solier (Coleoptera: Staphylinidae:
      Aleocharinae) with a checklist of all species of the genus.
AB  - Polylobus stigma (Erichson, 1839) is the only known species of the genus from
      Brazil. Here, this species is redescribed based on the type material, including
      illustrations of diagnostic characters. The species remains in Polylobus, but
      pending further revision of the genus and related genera as Tricolpochila
      Bernhauer, 1908 and Polylobinus Bernhauer, 1908. A commented checklist of all
      species in Polylobus is also provided. 

PMID- 24943161
TI  - Notes on the genus Acosmetura Liu, 2000 (Orthoptera: Tettigoniidae:
      Meconematinae).
AB  - This paper deals with one new species, Acosmetura mabianensis Bian & Shi sp.
      nov., one new combination, Acosmetura jinyunensis (Shi & Zheng, 1994) com. nov.,
      and the first record of female of Acometura nigrogeniculata (Liu & Wang, 1998).
      Photographs of two known species, a key to the species, male stridulatory files
      and a distribution map are provided. We also observe the male stridulatory files
      and left tegmina for four known species of the genus. The material is deposited
      in the Museum of Hebei University. 

PMID- 24943162
TI  - A new forest-dwelling Bent-toed Gecko (Squamata: Gekkonidae: Cyrtodactylus) from
      Doi Suthep, Chiang Mai Province, northern Thailand.
AB  - We describe a new forest-dwelling Cyrtodactylus from Doi Suthep, Chiang Mai
      Province, northern Thailand. Cyrtodactylus doisuthep sp. nov. is characterized by
      a maximal known SVL of 90.5 mm; 19 or 20 longitudinal rows of dorsal tubercles; a
      continuous series of 34 or 35 enlarged femoro-precloacal scales, including six or
      seven pitted scales on each femur (male and females) separated by a diastema from
      six pitted (females) or pore-bearing (male) precloacal scales; no precloacal
      groove or depression; transversely enlarged subcaudal scales; and six or seven
      irregular thin beige dorsal bands between limb insertions.  

PMID- 24943163
TI  - Hyalella cenotensis, a new species of Hyalellidae (Crustacea: Amphipoda) from the
      Yucatan Peninsula, Mexico.
AB  - In this study the first blind species of Hyalella for Mexico is described; it is
      the second in the genus to be recorded there. The new species is closer to the
      eyeless species: H. anophthalma Ruffo, 1957, H. muerta Baldinger, Shepard &
      Threloff, 2000, H. caeca Pereira, 1989, H. spelaea Bueno & Cardoso, 2011 in
      Cardoso et al. 2011, H. imbya Rodrigues & Bueno, 2012 in Rodrigues et al. 2012,
      but with no curved seta at the inner ramus of uropod 1, antennae 1 shorter than
      antennae 2, no apical setae on the telson and a characteristic dorsoposterior
      carina and three pappose setae on the inner plate of maxilla 1. The morphological
      intraspecific variations that can be found in this genus are discussed. 

PMID- 24943164
TI  - Description of the last stadium larva and female of Microgomphus thailandica
      Asahina, 1981 (Odonata: Gomphidae).
AB  - The last stadium larva of Microgomphus thailandica is described, illustrated and
      compared with the larvae of congeneric species based on reared specimens
      collected from the Phachi headwater stream, Ratchaburi province, Thailand. The
      female adult of this species is described for the first time from a reared
      specimen from the same locality. 

PMID- 24943165
TI  - The enigmatic genus Stenichnoteras scott from the seychelles (Coleoptera:
      Staphylinidae: Scydmaeninae).
AB  - The genus Stenichnoteras, known from the Seychelles and represented by a single
      known species, St. montanum, is redescribed and redefined. The morphological
      structures of St. montanum are described and illustrated in detail. Similarities
      and possible affinities with other genera of Cyrtoscydmini are discussed, and it
      is concluded that Stenichnoteras may be closely related to Euconnus, despite an
      apparent difference in the shape of prothorax and some mesoventral structures. 

PMID- 24943166
TI  - Revision of the genus Narvesus Stal, 1859 (Hemiptera: Heteroptera: Reduviidae:
      Stenopodainae) and a new record for Argentina.
AB  - This is a revision of Narvesus Stal, a Neotropical genus with two species:
      Narvesus carolinensis Stal 1859 and Narvesus minor Barber 1930. Both known
      species are redescribed and illustrated, including data on male genitalia and new
      distributional records. We compared with the genus Diaditus Stal. 

PMID- 24943167
TI  - Correction of the publication date of Lithocolletis Helianthemella Herrich
      Schaffer based on additional data of the taxonomic history of this species
      (Lepidoptera: Gracillariidae).
AB  - Recently De Prins et al. (2013) published a description of the new genus Triberta
      and transferred to it two species, T. cistifoliella (Groschke) and T.
      helianthemella (Herrich-Schaffer), formerly assigned to the genus Phyllonorycter
      Hubner. In the upcoming studies related to this new genus the need arose to
      clarify whether the publication year of T. helianthemella is 1860 or 1861 (Buszko
      1996, 2013; De Prins & De Prins 2005, 2013).  

PMID- 24943168
TI  - First record of the genus Baptista Distant, 1903 (Heteroptera: Veliidae) from
      China, with descriptions of two new species.
AB  - The genus Baptista Distant, 1903, is recorded for the first time from China. Four
      species are treated in this paper, with B. digitata Andersen, 1989 and B. hoedli
      Zettel, 2004 newly recorded from China and two additional species, B. curvicornis
      sp. n. and B. obtusa sp. n., described as new to science. Photographs of the male
      and female dorsal habitus, male fore legs, male abdominal sternites, and male
      genitalic structures are provided, accompanied by line drawings of the male fore
      tibial details, male paramere, habitat photographs, and a distribution map for
      all Baptista species. A key to all four species occurring in China is also
      provided to assist in future identification. 

PMID- 24943169
TI  - Species of the subgenus Chaetolabis, townes 1945 of the genus Chironomus, Meigen
      1803 (Diptera: Chironomidae), from a cytogenetic perspective.
AB  - The polytene chromosomes of three North American species in the subgenus
      Chaetolabis of the genus Chironomus are described and compared to the published
      karyotypes of two Palearctic species. Chironomus (Chaetolabis) atroviridis has
      four polytene chromosomes, like the Palearctic C. globulus, while C. ochreatus
      and the North American populations of C. bitumineus each have three chromosomes
      due to tandem fusion of arm G to arm E, as in the Palearctic populations of C.
      bitumineus. The results support the existence of distinct species, particularly
      clarifying that the names C. atroviridis, C. bitumineus and C. ochreatus cannot
      be synonyms, as was suggested by some previous workers. The question of whether
      Lobochironomus "sp. Ya6" might be conspecific with C. macani is also discussed. 

PMID- 24943170
TI  - Three new species of the subfamily Cladonotinae (Orthoptera: Tetrigidae) from
      Thailand.
AB  - The pygmy grasshopper subfamily Cladonotinae and genera Epitettix Hancock, 1907,
      Pseudepitettix Zheng, 1995 and Tuberfemurus Zheng, 1992 are firstly recorded from
      Thailand. Three new species, namely Epitettixobtusus obtusus sp. nov. from
      provinces Nakhon Ratchasima and Chiang Mai, Pseudepitettix pimkarnae sp. nov.
      from province Saraburi and Tuberfemurus kanokwanae sp. nov. from province
      Saraburi, are described. 

PMID- 24943171
TI  - Three new species of Kerevata (Braconidae: Rogadinae: Clinocentrini) from
      mainland Papua New Guinea.
AB  - Three new species of the distinctive, cyclostome, braconid wasp genus Kerevata
      (viz. Kerevata jamesmayi sp. nov., K. clarksoni sp. nov. and K. hammondi sp.
      nov.) from Mt Wilhelm, Madang Province, Papua New Guinea are described and
      illustrated, and a key provided to enable their identification and separation
      from the only other species described to date, K. pacifica, from New Britain in
      the Bismark Archipelago off the S. E. coast of New Guinea. Characters used to
      differentiate Kerevata from the related Confusocentrus are modified. 

PMID- 24943172
TI  - Key to species of leafhopper genus Drabescoides Kwon & Lee (Hemiptera,
      Cicadellidae), with description of a new species from southern China.
AB  - A new species Drabescoides complexa sp. nov. from Zhejiang and Fujian Provinces,
      China is described and illustrated, and can be distinguished by the unique
      aedeagus with pair of lamellae above a collar-shaped process on the shaft dorsal
      surface. A key to all species is given for identification based on the male
      genitalia along with a map showing the geographic distribution of the genus. 

PMID- 24943173
TI  - Two new species of Platypona DeLong (Hemiptera: Cicadellidae: Iassinae: Gyponini)
      from Peru and key to the species of the genus.
AB  - Two new species of the previously monotypic genus Platypona DeLong, 1982 from
      Peru are described and illustrated: P. furcata sp. nov. (Cusco Department) and P.
      inca sp. nov. (Pasco Department). These two species can be distinguished from
      each other, as well as from the type-species, P. sinverda DeLong, 1982, mainly by
      features of the style and aedeagus. A key to the three known species of Platypona
      is provided. 

PMID- 24943174
TI  - Description of a new species of the genus Henricohahnia Breddin (Hemiptera:
      Heteroptera: Reduviidae: Harpactorinae) from China, with a key to Chinese
      species.
AB  - Henricohahnia parva sp. nov. is described and illustrated based on the specimens
      collected from Yunnan Province of China. It represents the smallest-sized species
      of the genus Henricohahnia Breddin so far known. A key to the eight Chinese
      species of the genus is provided. 

PMID- 24943175
TI  - Lolodorfus, a new genus of net-winged beetles (Coleoptera: Lycidae: Dexorinae)
      from Cameroon.
AB  - A new genus Lolodorfus is proposed within the subfamily Dexorinae and Lolodorfus
      flavus sp. nov. from Cameroon is described. Illustrations of diagnostic
      characters are given. The genus Mimolibnetis Pic, 1936 is transferred to the
      Dexorinae Bocak et Bocakova, 1989, and consequently the subfamily Mimolibnetinae
      Kazantsev, 2013 is considered to be a younger synonym of Dexorinae Bocak et
      Bocakova, 1989. 

PMID- 24943176
TI  - The breeding behavior of Glyphoglossus molossus and the tadpoles of Glyphoglossus
      molossus and Calluella guttulata (Microhylidae).
AB  - The breeding behavior of Glyphoglossus molossus is described from still and video
      images taken in Cambodia. These large, burrowing frogs follow the general theme
      of microhylids that deposit aquatic eggs: explosive breeding in ephemeral water
      and performing multiple amplectic dips to oviposit surface films of pigmented
      eggs. A portion of a clutch is released with each dip, a dip lasts for about 6 s,
      200-300 eggs are released per dip, and about 5 s pass between dips. The ova have
      a dark black animal pole and yellow vegetal pole. Expanded datasets on the
      morphology of the tadpoles of Glyphoglossus from Vietnam and Calluella from
      Myanmar are presented.  

PMID- 24943177
TI  - A redescription of the type species of the jumping spider genus Pseudomaevia
      (Araneae: Salticidae) from Lord Howe Island, Australia.
AB  - The genus Pseudomaevia Rainbow, 1920 presently includes three forms, P. cognata
      Rainbow, 1920, P. insulana Berland, 1942 and P. i. aorai Berland, 1942, all found
      in the western Pacific region (Platnick 2014). The type species, P. cognata, was
      only briefly described with some poor illustrations of the male, but no
      information was given on the female. This situation makes placing species in this
      genus, or the genus in a wider context, difficult. The present work describes and
      illustrates both sexes of the type species. The female genitalia are unusual in
      that the insemination duct joins the fertilization duct without any apparent
      spermatheca. The subfamilial placement of the genus is unknown. 

PMID- 24943178
TI  - Pagurus Asper H. Milne Edwards, 1848, a subjective synonym of Clibanarius
      longitarsus (De Haan, 1849) and reversal of precedence (Crustacea: Decapoda:
      Anomura: Diogenidae).
AB  - The species-group name Pagurus longitarsus was proposed by De Haan (1849: 211,
      pl. 50, fig. 3) for a species of hermit crab collected from Japan (see Yamaguchi
      & Baba 1993: 272, 273). Dana (1852b: 464) transferred Pagurus longitarsus to the
      genus Clibanarius Dana, 1852 (first established in Dana 1852a). Dana (1852b: 464)
      also suggested that Pagurus longitarsus De Haan, 1849, and Pagurus asper H. Milne
      Edwards, 1848, were possibly synonymous by listing "Pagurus asper ? Edwards, Ann.
      des Sci. Nat., 1848(3), v. [sic] 62" in the synonymy of Pagurus longitarsus De
      Haan, 1849. Fize & Serene (1955: 72) repeated Dana's (1852b: 464) opinion
      regarding the synonymy Pagurus longitarsus and Pagurus asper. McLaughlin (2002:
      399) and McLaughlin et al. (2010: 20) also considered Pagurus longitarsus De
      Haan, 1849, and Pagurus asper H. Milne Edwards, 1848, to be possibly conspecific,
      but considered Clibanarius longitarsus (De Haan, 1849), to be the valid name. 

PMID- 24943179
TI  - A new record for Limnobatodes paradoxus Hussey, 1925 from Guyana (Hemiptera:
      Heteroptera: Hydrometridae: Limnobatodinae).
AB  - Limnobatodes paradoxus Hussey, 1925 is a primitive hydrometrid, described from a
      single female specimen collected in 1923 at Tela, Honduras (Hussey 1925).
      Following the original description, very few records of this species have been
      reported in literature, and locality indications are not detailed: Brazil (Cobben
      1968), Peru (Andersen 1977), and French Guiana (Polhemus & Polhemus 1995).
      Andersen (1977, 1982) quoted "British Honduras" [= Belize] instead of Honduras,
      and this mistake was subsequently repeated by Schuh and Slater (1995) (see
      Moreira, 2014). This taxon was not listed by Heckman (2011) in his monograph on
      the Heteroptera of South America. Excellent illustrations of this species, in
      comparison with those of other Heteroptera, have been provided by several authors
      (cf. Hussey 1925; Cobben 1968, 1978; Andersen 1977, 1982). Nothing is known about
      the habitat and life history of Limnobatodes paradoxus (Andersen 1977; Polhemus &
      Polhemus 1995). 

PMID- 24943180
TI  - A taxonomic review of the genus Junnanotrechus Ueno & Yin, 1993 (Coleoptera:
      Carabidae: Trechinae), with description of six new species.
AB  - Six new species of the genus Junnanotrechus Ueno & Yin, 1993 are described from
      Yunnan Province, southern China: J. wrasei sp. n. (from the Diancang Shan Mt.
      R.), J. triporus sp. n. (from the mountains east of Weishan), J. schuelkei sp. n.
      (from the Ailao Shan Mountain Range), J. elegantulus sp. n. (from the Daxueshan
      Mount east of Mengsa Town), J. oblongus sp. n. (from the Daxueshan Mount west of
      Niutoushan Village), J. koroleviellus sp. n. (from the mountains west of Yunxian
      Town). New taxa discovered allow a more precise definition of diagnostic
      characters for the genus. All species were extensively measured and morphometric
      indices are given. The members of the genus are keyed and their known
      distribution is mapped. Geographic patterns in transformations of major character
      states suggest the center of dispersal for members of the genus was, most likely,
      somewhere in the valley of the Mekong (=Lancang Jiang) River west of the Ailao
      Shan Mountain Range. 

PMID- 24943181
TI  - New species and new records of Pterosthetops: eumadicolous water beetles of the
      South African Cape (Coleoptera, Hydraenidae).
AB  - Pterosthetops is one of a number of hydraenid genera endemic to the Cape of South
      Africa, whose minute moss beetle fauna is amongst the most diverse on earth. Here
      seven species are described as new: Pterosthetops baini sp. nov., Pterosthetops
      coriaceus sp. nov., Pterosthetops indwei sp. nov., Ptersothetops pulcherrimus sp.
      nov., Pterosthetops swartbergensis sp. nov., Pterosthetops tuberculatus sp. nov.
      and Pterosthetops uitkyki sp. nov., all from mountains in the Western Cape
      region. New collection records are also provided for all five previously
      described members of the genus, together with a revised key. Pterosthetops appear
      to be specialist inhabitants of seepages over rock faces (hygropetric/madicolous
      habitats), rarely being found outside such situations. 

PMID- 24943182
TI  - Contribution to the freshwater gastrotrich fauna of wetland areas of southwestern
      Ontario (Canada) with redescriptions of seven species and a check-list for North
      America.
AB  - This study gives additional, detailed information on the freshwater gastrotrich
      species described and reported from the southwestern regions of Ontario and New
      Brunswick, Canada by Schwank (1990). Aspidiophorus ontarioniensis, Chaetonotus
      (Chaetonotus) furculatus, Chaetonotus (Chaetonotus) ontariensis, Chaetonotus
      (Primochaetus) annae, Ichthydium malleum, Lepidodermella forficulata and Setopus
      lemnicola are all redescribed. In addition, a complete list of freshwater species
      currently known from North America is given. 

PMID- 24943183
TI  - Review of the Southeast Asian millipede genus Enghoffosoma Golovatch, 1993
      (Diplopoda, Polydesmida, Paradoxosomatidae), with descriptions of new species.
AB  - The Southeast Asian millipede genus Enghoffosoma ranges from southern China in
      the north, western Myanmar in the west, and central Thailand and southern Laos in
      the south and east. It currently contains seven species, including five new ones,
      described in this paper: E. zebra sp. n., E. lanceolatum sp. n., E. anchoriforme
      sp. n., E. funda sp. n. and E. bispinum sp. n. The genus is rediagnosed, a key to
      all known species is given, and their distributions are mapped. 

PMID- 24943184
TI  - Redescription of late-instar larva of Ptinella aptera (Guerin-Meneville, 1839)
      (Coleoptera: Ptiliidae).
AB  - The late-instar larva of the featherwing beetle Ptinella aptera is redescribed. A
      coding system for chaetotaxic structures for ptiliid larvae is proposed and
      possible serial homology of setae across body segments is discussed. Previous,
      fragmentary and inaccurate descriptions of larval stages of P. aptera are
      discussed. The structures of immature P. aptera are compared with those of P.
      tenella and possible homologies and differences are indicated. 

PMID- 24943185
TI  - Amphipoda (Crustacea) from Palau, Micronesia: families Melphidippidae,
      Oedicerotidae, Photidae, Pleustidae, Podoceridae, Stenothoidae, Synopiidae and
      Talitridae.
AB  - Eleven species belonging to the families Melphidippidae, Oedicerotidae, Photidae,
      Pleustidae, Podoceridae, Stenothoidae, Synopiidae and Talitridae are recorded
      from Palau, Micronesia. Eight species are figured. One species is new to science
      and is described and figured. One species was previously known only from
      Australia, one only from Madagascar and one only from Fiji. 

PMID- 24943186
TI  - Neoeubria inbionis Shepard & Barr, a new genus and new species of neotropical
      water penny beetle (Coleoptera: Psephenidae: Eubriinae), with a key to the adult
      Eubriinae of the Neotropic Zone.
AB  - Neoeubria inbionis, new genus and new species, is described from Costa Rica,
      Nicaragua, Panama and Ecuador. All life stages are descibed and illustrated, and
      a key to adults of the Eubriinae genera of the Neotropics is provided. Neoeubria
      is one of the most basal genera of the Eubriinae. 

PMID- 24943187
TI  - A new species of triadal coral snake of the genus Micrurus Wagler, 1824
      (Serpentes: Elapidae) from northeastern Brazil.
AB  - The genus Micrurus comprises 123 currently recognized taxa (species and
      subspecies) that are traditionally arranged in four species groups diagnosable
      mainly by color pattern characteristics. Here, we describe a new species of
      triadal coral snake from northeastern Brazil. The new species is distinguished
      from other sympatric triadal congeners (M. lemniscatus carvalhoi, M. ibiboboca
      and M. brasiliensis) mainly by the entirely black parietals and by a suite of
      external characters and hemipenial morphology. The new species appears to be
      restricted to tropical ombrophilous lowland coastal forests of northeastern
      Brazil and all recently collected specimens are known to occur in small forest
      patches surrounded by periurban environment, which calls for an urgent evaluation
      on its conservation status. 

PMID- 24943188
TI  - New member of the family Niphargidae from Croatia, Niphargus radzai, sp. n.
      (contribution to the knowledge of the Amphipoda 273).
AB  - One new species of the genus Niphargus Schiodte, 1849 (Amphipoda, Gammaridea,
      Niphargidae) from the subterranean waters (springs) above Ravno Vrdovo in Dinara
      Mountain, Croatia, is described. Niphargus radzai sp. n. belongs to the
      artificial group within Niphargus with elevated number of setae along outer
      margin of dactylus in gnathopods 1 and 2 and dactylus of some or all pereopods
      provided with additional spines along inner margin. The differences between N.
      radzai and some other similar members of this group of taxa are discussed. 

PMID- 24943190
TI  - Epidemiology of fishborne trematodiasis in Kazakhstan.
AB  - Fish borne trematodes are an important cause of morbidity in Kazakhstan. The
      number of human cases of opisthorchiidosis (infection with parasites of the
      family opisthorchiidae) reached a peak of 2521 recorded cases (17 cases per
      100,000) in 2002 with a gradual decline to 1225 cases (7.4 cases per 100,000) in
      2011. Most human cases are found in the north and north east part of Kazakhstan
      in areas drained by the Irtysh River and it tributaries. A further focus is found
      in the north west in the Ural river basin in the European part of Kazakhstan. The
      most common occupations of patients with opisthorchiidosis included the manual
      laborers, those employed in the home or unemployed. Necropsy investigations of
      village dogs in an endemic region revealed 37 of 51 (72%) village dogs infected
      with either Opisthorchis felineus or Methorchis bilis. Likewise an investigation
      of 242 cats consisting of strays, village, suburban and city cats revealed 79
      (33%) animals infected with O. felineus. Higher prevalences were seen in strays
      and village cats compared to suburban cats. No urban cats, which lived in
      apartments, were found to be infected. Other important zoonoses included
      Echinococcus granulosus, detected in 2 of the 51 necropsied village dogs and E.
      multilocularis was found in 2 out of 124 necropsied stray cats. Investigations of
      locally caught fish revealed 10 of 107 (9%) roach (Rutilus rutilus), 49 of
      68(72%) ide (Leuciscus idus) and 2 of 79 (2.5%) bream (Abramis brama) infested
      with trematode metacercariae. No metacercariae were found in 609 crucian carp
      (Carassius carassius), 35 tench (Tinca tinca), 79 carp (Cyprinus carpio), 46
      perch (Perca fluviatilis) or 20 zander (Sander lucioperca). 

PMID- 24943194
TI  - Emergency physicians undergo a formal training in the use of ultrasound.

PMID- 24943191
TI  - Real-world cost-effectiveness of cetuximab in locally advanced squamous cell
      carcinoma of the head and neck.
AB  - Clinical trial EMR 62202-006 demonstrates prolonged median locoregional control
      (24.4 vs. 14.9 months), progression-free survival (17.1 vs. 12.4 months) and
      overall survival (49.0 vs. 29.3 months) for patients who receive cetuximab added
      to the comparator radiotherapy for locally advanced squamous cell carcinoma of
      the head and neck (LA SCCHN). In the Netherlands, hospitals receive reimbursement
      for cetuximab conditional on cost-effectiveness in daily practice. To estimate
      the real-world incremental cost per quality adjusted life-year (QALY) gained for
      radiotherapy + cetuximab over radiotherapy alone in first line treatment of LA
      SCCHN, a Markov model is constructed with health states "alive without
      progression", "alive following progression" and "death". Transition probabilities
      per month are estimated from clinical trial data and retrospectively collected
      real-world data from two Dutch head and neck cancer treatment centres (2007-2010,
      n = 141). 5-year, 10-year and lifetime horizons are used, without and with
      discounting (4 % costs, 1.5 % effects) to calculate incremental cost
      effectiveness ratios. Two scenarios explore different assumptions on prognosis of
      real-world versus trial patients. Adding cetuximab to radiotherapy results in
      increased costs and health gains in both scenarios and across each of the time
      horizons. Incremental costs per QALY gained range between <euro>14,624 and
      <euro>38,543 in the base-case. For a willingness to pay of <euro>80,000 per QALY,
      the acceptability curves for the different scenarios show probabilities between
      0.76 and 0.87 of radiotherapy + cetuximab being cost-effective compared to
      radiotherapy alone. Current results show the combined treatment of radiotherapy +
      cetuximab to be a cost-effective treatment option for patients with LA SCCHN.

PMID- 24943192
TI  - Downregulation of caveolin-1 in chronic rhinosinusitis with and without nasal
      polyps.
AB  - The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial.
      Recent evidence has suggested that caveolin-1 (Cav-1) is a 22 kDa scaffolding
      protein and plays a pivotal role in host defense against infections and tumour
      suppression by reducing production of cyclin D1 and endothelial nitric oxide
      synthase (eNOS). However, little is known about their roles in CRS. Therefore, we
      aimed to investigate the expression and role of Cav-1 in CRS. Cav-1 protein
      expression were investigated by immunohistochemistry method and mRNA expression
      of Cav-1, cyclin D1 and eNOS were assessed by real-time polymerase chain reaction
      in CRS and control subjects. Moreover, the effects of various stimulators with
      different concentrations and time on Cav-1 were evaluated on nasal explant
      culture. The results showed that weaker expression of Cav-1 protein and mRNA were
      observed in CRS, especially in CRS with nasal polyps (CRSwNP), stronger mRNA
      expression of cyclin D1 and eNOS were observed in CRS and Cav-1 expression was
      negatively related to cyclin D1 and eNOS expression, respectively. Cav-1 mRNA was
      augmented by IFN-gamma, but supressed by IL-4 and IL-1beta. In conclusion, the
      expression of Cav-1 was downregulated in CRS and the role of Cav-1 was impaired
      in CRS, especially in CRSwNP, leading to the attenuation of inhibition effect on
      cyclin D1 and eNOS and resulted in the overexpression of cyclin D1 and eNOS. IFN
      gamma may be essential for Cav-1 gene expression.

PMID- 24943193
TI  - Genetic variations in RORalpha are associated with chronic obstructive pulmonary
      disease.
AB  - Retinoic acid receptor-related orphan receptor-alpha (RORalpha) plays a key role
      in the regulation of lipid and cholesterol metabolism that has been implicated in
      the development of chronic obstructive pulmonary disease (COPD). The aim of this
      study was to determine the frequencies of single-nucleotide polymorphisms (SNPs)
      in RORalpha gene in a Chinese population and their possible association with COPD
      susceptibility. Nine tagging SNPs, including rs17270181, rs1898413, rs17270216,
      rs8033552, rs8036966, rs7169364, rs340002, rs340023 and rs11630262, were screened
      in 279 COPD patients and 367 controls by the SNaPshot method. Association
      analysis of genotypes and haplotypes constructed from these loci with COPD was
      conducted under different genetic models. Alleles or genotypes of rs8033552
      distributed significantly differently in COPD patients and controls (allele:
      P=0.0001, false discovery rate (FDR) Q=0.004, odds ratios (OR): 1.62 and 95%
      confidence interval (CI): 1.27-2.07; genotype: P=0.0005, FDR Q=0.008). The allele
      A at rs8033552 was potentially associated with an increased risk of COPD in
      additive model, displaying ORs of 1.62 (95% CI: 1.17-2.26, P=0.004, FDR Q=0.019)
      in subjects with genotypes AG vs GG and 2.69 (95% CI: 1.47-4.93, P=0.001, FDR
      Q=0.011) in subjects with genotypes AA vs GG, respectively. In haplotype
      analysis, we observed haplotypes GGAGATGTG and GGAGCTGTG had protective effects,
      whereas haplotypes GGAGATACA and GGAGATACG were significantly associated with the
      increased risk of COPD. These data suggest that RORalpha may be a potential risk
      gene for COPD. 

PMID- 24943195
TI  - Possible involvement of a tetrahydrobiopterin in photoreception for UV-B-induced
      anthocyanin synthesis in carrot.
AB  - Our previous studies of action spectra for UV-B-induced anthocyanin accumulation
      in cultured carrot cells indicated that a reduced form of pterin, possibly
      tetrahydrobiopterin, contributes to UV-B photoreception. In this report, we
      provide additional evidence for the involvement of pterin in UV-B light sensing.
      UV-B-induced phenylalanine ammonia-lyase (PAL) activity was considerably
      suppressed by N-acetylserotonin (an inhibitor of tetrahydrobiopterin
      biosynthesis), and this suppression was partially recovered by adding biopterin
      or tetrahydrobiobiopterin. In addition, protein(s) specifically bound to
      biopterin were detected by radiolabeling experiments in N-acetylserotonin-treated
      cells. Furthermore, diphenyleneiodonium, a potent inhibitor of electron transfer,
      completely suppressed UV-B-induced PAL activity. These results suggest the
      occurrence of an unidentified UV-B photoreceptor (other than UVR8, the tryptophan
      based UV-B sensor originally identified in Arabidopsis) with reduced pterin in
      carrot cells. After reexamining published action spectra, we suggest that
      anthocyanin synthesis is coordinately regulated by these two UV-B sensors. 

PMID- 24943196
TI  - Obesity and functional gastrointestinal diseases in children.

PMID- 24943198
TI  - Preparation of CO2/diene copolymers: advancing carbon dioxide based materials.

PMID- 24943197
TI  - Nitroglycerine and patient position effect on central, hepatic and portal venous
      pressures during liver surgery.
AB  - BACKGROUND: To reduce blood loss during liver surgery, a low central venous
      pressure (CVP) is recommended. Nitroglycerine (NG) with its rapid onset and
      offset can be used to reduce CVP. In this study, the effect of NG on portal and
      hepatic venous pressures (PVP and HVP) in different body positions was assessed.
      METHODS: Thirteen patients undergoing liver resection were studied. Cardiac
      output (CO), mean arterial pressure (MAP) and CVP were measured. PVP and HVP were
      measured using tip manometer catheters at baseline (BL) in horizontal position;
      during NG infusion, targeting a MAP of 60 mmHg, with NG infusion and the patient
      placed in 10 head-down position. RESULTS: NG infusion reduced HVP from 9.7 +/-
      2.4 to 7.2 +/- 2.4, PVP from 12.3 +/- 2.2 to 9.7 +/- 3.0 and CVP from 9.8 +/- 1.9
      to 7.2 +/- 2.1 mmHg at BL. Head-down tilt during ongoing NG resulted in increases
      in HVP to 8.2 +/- 2.1, PVP to 10.7 +/- 3 and CVP to 11 +/- 1.9 mmHg. CO at BL was
      6.3 +/- 1.1, which was reduced by NG to 5.8 +/- 1.2. Head-down tilt together with
      NG infusion restored CO to 6.3 +/- 1.0 l/min. CONCLUSION: NG infusion leads to
      parallel reductions in CVP, HVP and PVP at horizontal body position. Thus, CVP
      can be used to guide NG dosage and fluid administration at horizontal position.
      NG infusion can be used to reduce HVP. Head-down tilt can be used during NG
      infusion to improve both blood pressure and CO without substantial increase in
      liver venous pressure. In head-down tilt, CVP dissociates from HVP and PVP.

PMID- 24943199
TI  - Aromaticity of the planar hetero[8]circulenes and their doubly charged ions: NICS
      and GIMIC characterization.
AB  - A series of planar hetero[8]circulenes and their doubly charged ions are studied
      by the NICS and GIMIC methods to interpret the aromatic properties of these high
      symmetry species. In accordance with the performed calculations all studied
      hetero[8]circulenes are found to be nonaromatic compounds because paratropic and
      diatropic ring-currents are completely canceled yielding almost zero net current.
      In great contrast, the dicationic and dianionic hetero[8]circulenes demonstrate
      the predominant contribution of diatropic ring currents resulting in the total
      aromatic character of the studied doubly charged ions. This fact allows us to
      predict the high stability of dianionic hetero[8]circulenes and explains the
      extremely high stability of dicationic species observed in the mass-spectra. 

PMID- 24943200
TI  - Dynamical footprint of falcipain-2 catalytic triad in hemoglobin-beta-bound
      state.
AB  - Falcipain-2 (FP-2) is a member of papain family of cysteine proteases and the
      major hemoglobinase of the hemoglobin detoxification and hemozoin polymerization
      complex localized in the food vacuole of the plasmodium species. FP-2 is
      currently gaining clinical significance as the drug target of choice in combating
      malaria epidemic. Here, a theoretical FP-2/hemoglobin complex has been proposed
      and the dynamical footprint and energetics of binding have been investigated
      using molecular and quantum mechanics approaches. The mapped interaction
      interface comprises residues 34-51 of hemoglobin and cysteine-42/histidine
      174/glutamine-36/asparagine-173/204 and subsites S1, S1', and S3 of FP-2. In
      hemoglobin-bound FP-2, asparagine-173 preferentially partners histidine-174,
      while glutamine-36 is preferred in ligand-free state. Cysteine-42 exhibits
      dihedral switch from 110 degrees  to 30 degrees  in free and bound states,
      respectively, with exclusion of water from the binding core upon hemoglobin
      binding. Hemoglobin similarly exhibits high occupancy within .2 nm distance with
      charged amido acid-rich subsites S1 and S3 of FP-2 functioning in tandem to
      reduce conformational flexibility of hemoglobin and facilitate the formation of a
      stabilizing anti-parallel beta-sheet between Leucine-172-valine-176 of FP-2 and
      phenylalanine-45-asparate-47 of hemoglobin and to overcome the + 1.13e + 5 eV
      activation energy required to optimize the FP-2/hemoglobin-beta conformation that
      precedes hydrolysis.

PMID- 24943203
TI  - Primary cutaneous follicle center lymphoma with follicular mucinosis.

PMID- 24943201
TI  - Review of preclinical studies on treatment of mucositis and associated pain.
AB  - Oral mucositis is a significant problem in cancer patients treated with radiation
      or chemotherapy, often hindering definitive cancer treatment. For patients with
      oral mucositis, pain is the most distressing symptom, leading to loss of
      orofacial function and poor quality of life. While oral mucositis has been well
      described, its pathophysiology is poorly understood. Oral health professionals
      treating patients with mucositis have almost no effective therapies to treat or
      prevent oral mucositis. The purpose of this review is to (1) describe the current
      preclinical models of oral mucositis and their contribution to the understanding
      of mucositis pathophysiology, (2) explore preclinical studies on therapies
      targeting mucositis and discuss the clinical trials that have resulted from these
      preclinical studies, and (3) describe the proposed pathophysiology of oral
      mucositis pain and preclinical modeling of oral mucositis pain. 

PMID- 24943202
TI  - Association between Serum Antibodies to Oral Microorganisms and Hyperglycemia in
      Adults.
AB  - We conducted a cross-sectional analysis to evaluate the relationship between
      serum antibody titers against 19 selected oral microorganisms and measures of
      hyperglycemia in a large, nationally representative data set. The study
      population consisted of 7,848 participants from the National Health and Nutrition
      Examination Survey III (1988-1994) who were at least 40 yrs old, with complete
      serum IgG antibody data against 19 oral microorganisms. The 19 antibody titers
      were grouped into 4 categories via cluster analysis--orange-red, yellow-orange,
      orange-blue, and red-green--named to reflect predominant antibody titers against
      microorganisms in Socransky's classification scheme for oral microbes. Linear
      regression models weighted for complex survey design were used in which fasting
      blood glucose, fasting insulin, and HbA1c were outcomes and antibody cluster
      scores were exposures, adjusting for potential confounders. Higher orange-red
      cluster scores were associated with increased hyperglycemia, while higher orange
      blue cluster scores were related with decreased hyperglycemia. A 1-unit-higher
      orange-red cluster score was associated with 0.46 mg/dL higher fasting blood
      glucose (p = .0038), and a 1-unit-higher orange-blue cluster score was associated
      with 0.34% lower HbA1c (p = .0257). Groups of antibody titers against periodontal
      microorganisms were associated with hyperglycemia independent of known risk
      factors.

PMID- 24943204
TI  - Psychometric validation of symptom severity measures in irritable bowel syndrome
      with constipation.
AB  - BACKGROUND: Historically, measures of symptom severity of irritable bowel
      syndrome with constipation (IBS-C) in clinical trials have not met the evidence
      requirements described in the FDA guidance on patient-reported outcomes (PROs),
      which describes the evidentiary requirements and review criteria for patient
      reported outcome measures intended to support product approval or labelling
      claims. AIM: Data from two phase 3 trials (N = 1608) of linaclotide for the
      treatment of IBS-C were analysed to evaluate the psychometric properties of
      patient-reported outcome measures assessing changes in the severity of abdominal
      and bowel symptoms. METHODS: A set of patient-reported outcome assessments
      addressing abdominal and bowel symptoms, the IBS-C Symptom Severity Measures,
      were administered daily using interactive voice response system technology.
      Intraclass correlation coefficients (ICCs), Pearson correlations, factor
      analyses, F-tests and effect sizes were computed to evaluate the reliability,
      construct validity, discriminating ability and responsiveness of the IBS-C
      Symptom Severity Measures in a clinical trial context. RESULTS: The IBS-C Symptom
      Severity Measures showed highly satisfactory test-retest reliability (ICCs
      ranging from 0.79 to 0.95) and construct validity. Factor analyses indicated one
      factor for abdominal symptoms and another for bowel symptoms. Known-groups F
      tests comparing subgroups based on various responder definitions were
      statistically significant and in the expected direction, substantiating the
      discriminating ability of the IBS-C Symptom Severity Measures. Responsiveness
      statistics (ranging from 0.6 to 2.1) demonstrated these measures are also capable
      of detecting change. CONCLUSIONS: The psychometric analysis results strongly
      support the reliability, construct validity, discriminating ability and
      responsiveness of the IBS-C Symptom Severity Measures and substantiate the
      conclusion of linaclotide treatment benefit.

PMID- 24943205
TI  - Use of azathioprine in IBD: modern aspects of an old drug.

PMID- 24943206
TI  - A retrospective cohort study of tinea pedis and tinea unguium in inpatients in a
      psychiatric hospital.
AB  - We conducted a retrospective cohort study on clinical and mycological features of
      tinea pedis and tinea unguium in psychiatric inpatients in Japan. Of the 317
      inpatients (152 with schizophrenia and 165 with depression), 46.1% had tinea
      pedis and 23.7% had tinea unguium. Of those with tinea pedis, 48.6% also had
      tinea unguium. The most common clinical type of tinea pedis was the combination
      of interdigital type and hyperkeratotic type. The mean clinical score of tinea
      pedis was 5.9, and that of tinea unguium based on the Scoring Clinical Index for
      Onychomycosis (SCIO) was 15.8. The main causative species of tinea pedis were
      Trichophyton rubrum (68.4%) and T. mentagrophytes (26.3%). No statistically
      significant differences were observed in incidence rates of tinea pedis or tinea
      unguium between men and women or between patients with schizophrenia and those
      with depression. As for incidence rates by age, patients with depression showed a
      single peak for tinea pedis and / or tinea unguium in their 50's, while patients
      with schizophrenia exhibited twin peaks for tinea pedis and / or tinea unguium in
      their 50's and 70's. Both tinea pedis and tinea unguium tended to become more
      severe in patients with chronic schizophrenia. Our study suggests that
      schizophrenia and depression, like diabetes mellitus and HIV infections, should
      be regarded as risk factors for tinea pedis and tinea unguium. 

PMID- 24943207
TI  - Detection of Mucor velutinosus in a blood culture after autologous peripheral
      blood stem cell transplantation : a pediatric case report.
AB  - Filamentous fungi were detected in the blood culture of a one-year-old boy after
      autologous peripheral blood stem cell transplantation. The patient was suspected
      to have aspergillosis and received micafungin. Fungi were isolated on potato
      dextrose agar medium and incubated at 37C for 2-5 days. Grayish, cottony colonies
      formed. A slide culture showed a spherical sporangium at the tips of the
      sporangiophores. The fungus could have been a zygomycete. The zygomycete was
      isolated from three blood cultures. The antifungal drug was changed from
      micafungin to liposomal amphotericin B, which resulted in an improvement in the
      patient's symptoms. Growth was observed at 37C, but not 42C in a growth
      temperature test. Gene sequence analysis identified the fungus as Mucor
      velutinosus. To the best of our knowledge, this is the first time M. velutinosus
      has been detected in Japan, and this case is very rare. Zygomycetes are known to
      be pathogens that cause fungal infections in immunodeficient patients such as
      those with leukemia. They are difficult to identify by culture and are identified
      at autopsy in many cases. Therefore, culture examinations should be performed for
      immunodeficient patients with the consideration of zygomycetes. 

PMID- 24943208
TI  - Antifungal susceptibility testing method for dermatophytes -determination of MIC
      and MFC values.
AB  - In vitro antifungal susceptibility of pathogenic fungi is important information
      for physicians when selecting an appropriate antifungal drug, deciding the route
      of drug administration, surveying resistant strains, and so on. Although both the
      minimum inhibitory concentration (MIC) and the minimum fungicidal concentration
      (MFC) are well known endpoints of antifungal susceptibility, the MIC is by far
      the more highly referred in clinical laboratories. In fact, while methods for
      determining the MIC have been standardized in Japan and the West to ensure
      accuracy and reproducibility of the results, by contrast, scant attention has
      been paid to standardizing methods for determining the MFC. The same preference
      for MIC topical antifungal drugs for dermatophytes are concerned. In 1999, the
      Japanese Society of Medical Mycology published a new, standardized method of
      testing the MIC for dermatophytes and this has since been widely adopted.
      Nonetheless, the fact remains that the MFC is still determined using methods
      derived from antifungal pharmacology. Recently in Japan, however, the MFC of
      topical antifungal drugs has begun attracting more attention due to the
      development of new antifungal agents with fungicidal activity. These new
      developments call for improving our understanding of both the MIC and MFC as
      endpoints of antifungal susceptibility, and for standardizing methods for
      determining the MFC.The present paper has two objectives : first, to overview the
      MIC and MFC for topical drugs as endpoints of antifungal susceptibility; and
      second, to describe a novel test based on the standardized broth microdilution
      method combined with the trans-well system and neutral red, which we recently
      developed in our laboratory for directly measuring the MFC.

PMID- 24943209
TI  - Deep-seated mycosis.

PMID- 24943210
TI  - Can persistent toenail fungus be successfully treated with a laser?
AB  - Onychomycosis is a common disease seen in dermatology practice. Most patients
      with onychomycosis opt for treatment due to the social stigma attached to the
      unsightly appearance, as well as the pain that can at times make walking
      difficult. However, in many cases, onychomycosis is resistant to oral antifungal
      medication, which is the first-line therapy for this disease. In recent years, we
      have attempted a new treatment method using a long-pulsed 1,064nm Nd :YAG laser
      (Cutera Inc., Brisbane, CA, USA) in refractory cases with onychomycosis. Using 1)
      a laser beam with a spot size of 5.0 mm and 2) sequential irradiation at low
      fluence, we 3) applied the laser to the infected lesions in a motion similar to
      showering, while maintaining a distance of several centimeters from the skin
      (Laser Genesis(TM)). Treatment efficacy was assessed using nail turbidity scores
      on a five-point scale. Improvement in onychomycosis was noted in more than 68.8%
      of all cases, thus demonstrating the high efficacy of this method. No major
      adverse reactions were observed during the treatment period. Since its mechanism
      of action clearly differs from that of antifungal agents, it can be considered a
      useful treatment option for cases with onychomycosis resistant to antifungal
      therapy. Future studies should examine "combined therapy" with oral / topical
      antifungal agents and this laser treatment, which may provide a significant
      improvement in the level of satisfaction among patients with onychomycosis.

PMID- 24943211
TI  - Historic topics on classification of Trichophyton mentagrophytes complex.
AB  - D. Gruby (1842-1844) detected the fungus in tinea as a causative agent and C.P.
      Robin (1853) described Microsporum mentagrophytes that was transferred to
      Trichophyton by Blanchard (1896). Sabouraud (1910) established a group of
      ectothrix microide which was divided into gypseum type (6 species: T. asteroids,
      T. granulosum, T. lacticolor and 3 species) and niveum type (T. radians and T.
      denticulatum). Thereafter, Epidermophyton simii Pinoy, 1912 and T. interdigitale
      Priestly, 1917 were reported. These species were classified as T. mentagrophytes
      by C.W. Emmons (1934 and 1940). Arthroderma simii Stockdale et al., 1965, A.
      benhamiae, Ajello and Cheng, 1967 and A. vanbreuseghemii Takashio, 1973 were
      discovered as teleomorphs of T. simii, T. mentagrophytes var. granulosum and T.
      mentagrophytes (mainly granulosum-asteroides form), respectively. Makimura et
      al., (1998) reported phylogenetic classification of T. mentagrophytes complex
      strains based on DNA sequences of nuclear ribosomal internal transcribed spacer 1
      (ITS1) regions, indicating that A. vanbreuseghemii and T. interdigitale belong to
      the same clade that was later named T. interdigatale by Graser et al.(1999). This
      naming has confused medical and veterinary doctors since anthropophilic isolates
      (T. interdigitale) and zoophilic isolates (A. vanbreuseghemii) were included as
      the same species.

PMID- 24943213
TI  - Term 2.

PMID- 24943212
TI  - Two cases of dermatophytosis caused by Microsporum gypseum and isolation of
      Microsporum gypseum from soil in Chigasaki city.
AB  - We report two cases of dermatophytosis caused by Microsporum (M.) gypseum. One
      case was a 59-year-old healthy woman who complained of itchy annular erythema on
      her right forearm. We isolated M. gypseum from scales on the forearm. The other
      case was a 73-year-old midwife who had developed infiltrated erythema on her face
      for 6 months. M. gypseum was isolated from scales of the nose. Both women liked
      gardening and M. gypseum was isolated from the garden soil of these women by a
      hair-baiting technique. The first case had a cat, a mouse and an owl, and the
      second had a dog. Hairbrush culture of these pets, however, was negative. So we
      concluded both cases were infected with M. gypseum from garden soil. We isolated
      M. gypseum from soil collected in Chigasaki city. Of the 7 fungal cultures from
      10 samples, 2 cultures were identified as M. gypseum.

PMID- 24943214
TI  - Autologous tumor vaccine modified with recombinant new castle disease virus
      expressing IL-7 promotes antitumor immune response.
AB  - Autologous tumor vaccine modified with nonlytic Newcastle disease virus (ATV-NDV)
      is a promising vaccine for cancer immunotherapy. IL-7 plays a critical role in
      lymphocyte development and homeostasis. To improve the efficacy of ATV-NDV, we
      inserted the murine IL-7 gene into the genome of nonlytic NDV strain LX using
      reverse genetic system. The insertion of the IL-7 gene neither affected the main
      features of NDV replication nor its tumor selectivity. The gene product was
      biologically active and stable. Then we tested the antitumor effects of the
      autologous tumor vaccine modified with LX/(IL-7) in the murine tumor models. We
      showed that tumor cells modified with LX/IL-7 induced a strong antitumor activity
      both in prophylaxis and therapeutic models. The IFN-gamma production and the
      cytotoxicity of tumor-specific CD8(+) T cells were significantly enhanced after
      immunization with tumor cells modified with LX/(IL-7) in both models. Although
      the tumor-infiltrating CD4(+) T cells and CD8(+) T cells were both increased and
      their IFN-gamma productions also were upregulated, the antitumor activity of the
      tumor vaccine modified with LX/(IL-7) was dependent on CD8(+) T cells. Our
      results demonstrated that the autologous tumor vaccine modified with NDV strain
      LX/(IL-7) could promote the antitumor immune responses mediated by CD8(+) T cells
      and significantly improve the efficacy of the ATV-NDV. 

PMID- 24943215
TI  - Development of innate CD4+ and CD8+ T cells in Itk-deficient mice is regulated by
      distinct pathways.
AB  - T cell development in the thymus produces multiple lineages of cells, including
      innate T cells such as gammadelta TCR(+) cells, invariant NKT cells, mucosal
      associated invariant T cells, and H2-M3-specific cells. Although innate cells are
      generally a minor subset of thymocytes, in several strains of mice harboring
      mutations in T cell signaling proteins or transcriptional regulators,
      conventional CD8(+) T cells develop as innate cells with characteristics of
      memory T cells. Thus, in Itk-deficient mice, mature CD4(-)CD8(+) (CD8 single
      positive [SP]) thymocytes express high levels of the transcription factor
      eomesodermin (Eomes) and are dependent on IL-4 being produced in the thymic
      environment by a poorly characterized subset of CD4(+) thymocytes expressing the
      transcriptional regulator promyelocytic leukemia zinc finger. In this study, we
      show that a sizeable proportion of mature CD4(+)CD8(-) (CD4SP) thymocytes in itk(
      /-) mice also develop as innate Eomes-expressing T cells. These cells are
      dependent on MHC class II and IL-4 signaling for their development, indicating
      that they are conventional CD4(+) T cells that have been converted to an innate
      phenotype. Surprisingly, neither CD4SP nor CD8SP innate Eomes(+) thymocytes in
      itk(-/-) or SLP-76(Y145F) mice are dependent on gammadelta T cells for their
      development. Instead, we find that the predominant population of Eomes(+) innate
      itk(-/-) CD4SP thymocytes is largely absent in mice lacking CD1d-specific
      invariant NKT cells, with no effect on innate itk(-/-) CD8SP thymocytes. In
      contrast, both subsets of innate Eomes(+)itk(-/-) T cells require the presence of
      a novel promyelocytic leukemia zinc finger-expressing, SLAM family receptor
      adapter protein-dependent thymocyte population that is essential for the
      conversion of conventional CD4(+) and CD8(+) T cells into innate T cells with a
      memory phenotype. 

PMID- 24943218
TI  - Regulatory T cells restrain CD4+ T cells from causing unregulated immune
      activation and hypersensitivity to lipopolysaccharide challenge.
AB  - Regulatory T cells (Tregs) are essential for maintenance of peripheral tolerance,
      and defects in Treg function have been linked to several autoimmune diseases. We
      previously reported that depletion of Tregs resulted in mortality to an otherwise
      nonlethal dose of LPS or Escherichia coli challenge. In this study, we
      investigated the mechanism by which Treg depletion leads to enhanced
      susceptibility to LPS. Using different murine lymphocyte gene knockout models, we
      show that the enhanced sensitivity to LPS following Treg depletion is mediated by
      T cells. SCID or RAG1-deficient mice, which lack T and B cells, do not show
      enhanced susceptibility to LPS. However, reconstitution of SCID mice with wild
      type CD4(+) T cells restored Treg depletion-induced sensitivity to LPS. This
      CD4(+) T cell-mediated hypersensitivity to LPS challenge in the absence of Tregs
      was also observed upon reconstitution of SCID mice with CD4(+) T cells from CD25
      knockout mice (which lack functional Tregs). Additionally, depletion of Tregs
      leads to increased CD4(+) T cell proliferation and proinflammatory cytokine
      production in response to LPS challenge. Some CD4(+) T cells express TLR4, and
      pretreatment of CD4(+) T cells with LPS dramatically enhanced their ability to
      induce inflammatory cytokine production by macrophages. Collectively, our results
      indicate that in the absence of functional Tregs, CD4(+) T cells are pathologic
      and contribute to exaggerated immune activation that is detrimental for survival
      in LPS-induced acute inflammation. Our data also provide evidence for direct
      activation of CD4(+) T cells by LPS through TLR4. 

PMID- 24943216
TI  - Humanized mice as a model for aberrant responses in human T cell immunotherapy.
AB  - Immune-deficient mice, reconstituted with human stem cells, have been used to
      analyze human immune responses in vivo. Although they have been used to study
      immune responses to xenografts, allografts, and pathogens, there have not been
      models of autoimmune disease in which the mechanisms of the pathologic process
      can be analyzed. We have found that reconstituted "humanized" mice treated with
      anti-CTLA-4 Ab (ipilimumab) develop autoimmune disease characterized by
      hepatitis, adrenalitis, sialitis, anti-nuclear Abs, and weight loss. Induction of
      autoimmunity involved activation of T cells and cytokine production, and
      increased infiltration of APCs. When anti-CTLA-4 mAb-treated mice were cotreated
      with anti-CD3 mAb (teplizumab), hepatitis and anti-nuclear Abs were no longer
      seen and weight loss did not occur. The anti-CD3 blocked proliferation and
      activation of T cells, release of IFN-gamma and TNF, macrophage infiltration, and
      release of IP-10 that was induced with anti-CTLA-4 mAb. We also found increased
      levels of T regulatory cells (CD25(+)CD127(-)) in the spleen and mesenteric lymph
      nodes in the mice treated with both Abs and greater constitutive phosphorylation
      of STAT5 in T regulatory cells in spleen cells compared with mice treated with
      anti-CTLA-4 mAb alone. We describe a model of human autoimmune disease in vivo.
      Humanized mice may be useful for understanding the mechanisms of biologics that
      are used in patients. Hepatitis, lymphadenopathy, and other inflammatory sequelae
      are adverse effects of ipilimumab treatment in humans, and this study may provide
      insights into this pathogenesis and the effects of immunologics on autoimmunity. 

PMID- 24943219
TI  - GM-CSF-licensed CD11b+ lung dendritic cells orchestrate Th2 immunity to Blomia
      tropicalis.
AB  - The Blomia tropicalis dust mite is prevalent in tropical and subtropical regions
      of the world. Although it is a leading cause of asthma, little is known how it
      induces allergy. Using a novel murine asthma model induced by intranasal exposure
      to B. tropicalis, we observed that a single intranasal sensitization to B.
      tropicalis extract induces strong Th2 priming in the lung draining lymph node.
      Resident CD11b(+) dendritic cells (DCs) preferentially transport Ag from the lung
      to the draining lymph node and are crucial for the initiation of Th2 CD4(+) T
      cell responses. As a consequence, mice selectively deficient in CD11b(+) DCs
      exhibited attenuated Th2 responses and more importantly did not develop any
      allergic inflammation. Conversely, mice deficient in CD103(+) DCs and CCR2
      dependent monocyte-derived DCs exhibited similar allergic inflammation compared
      with their wild-type counterparts. We also show that CD11b(+) DCs constitutively
      express higher levels of GM-CSF receptor compared with CD103(+) DCs and are thus
      selectively licensed by lung epithelial-derived GM-CSF to induce Th2 immunity.
      Taken together, our study identifies GM-CSF-licensed CD11b(+) lung DCs as a key
      component for induction of Th2 responses and represents a potential target for
      therapeutic intervention in allergy. 

PMID- 24943217
TI  - TCR affinity and tolerance mechanisms converge to shape T cell diabetogenic
      potential.
AB  - Autoreactive T cells infiltrating the target organ can possess a broad TCR
      affinity range. However, the extent to which such biophysical parameters
      contribute to T cell pathogenic potential remains unclear. In this study, we
      selected eight InsB9-23-specific TCRs cloned from CD4(+) islet-infiltrating T
      cells that possessed a relatively broad range of TCR affinity to generate NOD TCR
      retrogenic mice. These TCRs exhibited a range of two-dimensional affinities (~
      10(-4)-10(-3) MUm(4)) that correlated with functional readouts and responsiveness
      to activation in vivo. Surprisingly, both higher and lower affinity TCRs could
      mediate potent insulitis and autoimmune diabetes, suggesting that TCR affinity
      does not exclusively dictate or correlate with diabetogenic potential. Both
      central and peripheral tolerance mechanisms selectively impinge on the
      diabetogenic potential of high-affinity TCRs, mitigating their pathogenicity.
      Thus, TCR affinity and multiple tolerance mechanisms converge to shape and
      broaden the diabetogenic T cell repertoire, potentially complicating efforts to
      induce broad, long-term tolerance.

PMID- 24943227
TI  - Prescription charges: are they worth it?

PMID- 24943222
TI  - Cytotechnologist performance for detecting nuclear atypia in indeterminate
      thyroid fine needle aspirates.
AB  - INTRODUCTION: The thyroid gland is arguably the fastest growing anatomic site for
      fine needle aspiration (FNA). With the increase of thyroid cases, a reevaluation
      of cytotechnologist screening quality metrics in terms of thyroid FNA is called
      for. We present our institutional cytotechnologist performance at screening for
      nuclear atypia by applying established quality metrics. MATERIALS AND METHODS:
      Information on 8,814 consecutive thyroid cytopathology cases over a 10-year
      period was retrieved from computerized records. A subsample of cases categorized
      either as atypia of uncertain significance with nuclear atypia or suspicious for
      malignancy with features suspicious for papillary thyroid carcinoma. The
      cytotechnologist and cytopathologist diagnoses were compared using step
      discrepancies and Delta-ratios. RESULTS: Overall discrepancy between the
      cytotechnologist and cytopathologist diagnoses existed in <10% of all thyroid
      cases. One-category discrepancies were the most common (7.8%), while two-category
      discrepancies were rare (0.5%). The one-category discrepancy rate correlated with
      cytotechnologist experience. One-category under calls were twice as common as
      over calls (5.3 vs. 2.5%, p < 0.0001). CONCLUSIONS: We identified a high level of
      quality in the screening for nuclear atypia in thyroid FNA. The one-category
      discrepancy rate is suited to tracking individual cytotechnologist performance,
      identifies outliers and appears to correlate with cytotechnologist experience.

PMID- 24943220
TI  - Human Th2 but not Th9 cells release IL-31 in a STAT6/NF-kappaB-dependent way.
AB  - IL-31, a member of the IL-6 protein family, is one of the latest additions to the
      list of T cell-derived cytokines. Th2 cells are regarded as a main source of IL
      31, which is produced in response to stimulation by IL-4. Because the development
      of Th9 cells also requires IL-4 as a polarizing cytokine, the current study
      investigates IL-31 production in human Th9 cells compared with Th2 cells. We
      found that, although Th9 cells were able to release IL-31 during the first weeks
      of in vitro polarization, no IL-31 was detected in Th9 cultures after a final
      restimulation in the absence of polarizing cytokines. We further show that TGF
      beta, which is required to obtain Th9 cells in vitro, potently inhibits the
      release of IL-31 from Th2 cells, whereas IL-33, a cytokine associated with Th2
      mediated inflammation, synergizes with IL-4 in inducing IL-31 secretion. To
      analyze the molecular mechanisms underlying the induction of IL-31, EMSAs,
      reporter gene assays, and small interfering RNA-based silencing experiments were
      carried out. We show that STAT6 and NF-kappaB are central players in mediating IL
      31 expression induced by IL-4/IL-33. In addition, we identified a novel NF-kappaB
      binding element within the Il31 promoter that mediates the enhancing effects of
      IL-33 on IL-4/STAT6-induced IL-31 expression in human Th2 cells. Taken together,
      this study shows that IL-4 is essential for the production of IL-31, whereas TGF
      beta significantly suppresses IL-31 expression at the mRNA and protein levels. As
      a consequence, in vitro polarized Th2 cells, but not Th9 cells, are able to
      release IL-31. 

PMID- 24943224
TI  - Visible-light-enhanced Suzuki-Miyaura coupling reaction by cooperative
      photocatalysis with an Ru-Pd bimetallic complex.
AB  - A photo-assisted Suzuki-Miyaura coupling reaction has been realized by a molecule
      Pd(II) complex containing a Ru(II)-polypyridyl derivative as a visible light
      photosensitizing unit, where an electron transfer from excited Ru species to Pd
      forms an active electron rich Pd(0) and facilitates the oxidative addition step
      with aryl halides.

PMID- 24943223
TI  - Loss of TIMP3 exacerbates atherosclerosis in ApoE null mice.
AB  - BACKGROUND: Tissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein
      that inhibits the activity of various proteases and receptors. We have previously
      shown TIMP3 to be downregulated in metabolic and inflammatory disorders, such as
      type 2 diabetes mellitus. We have now generated an ApoE(-/-)Timp3(-/-) mouse
      model in which, through the use of genetics, metabolomics and in-vivo
      phenotypical analysis we investigated the role of TIMP3 in the development of
      atherosclerosis. METHODS AND RESULTS: En face aorta analysis and aortic root
      examination showed that ApoE(-/-)Timp3(-/-) mice show increased atherosclerosis
      with increased infiltration of macrophages into the plaque. Serum concentration
      of MCP-1 were elevated in the serum of ApoE(-/-)Timp3(-/-) mice coupled with an
      expansion of the inflammatory (M1) Gr1+ macrophages, both in the circulation and
      within the aortic tissue. Targeted analysis of metabolites revealed a trend to
      reduced short chain acylcarnitines. CONCLUSIONS: Our study shows that lack of
      TIMP3 increases inflammation and polarizes macrophages towards a more
      inflammatory phenotype resulting in increased atherosclerosis.

PMID- 24943230
TI  - Lead exposure from backyard chicken eggs: a public health risk?
AB  - Although the USA has made significant strides in reducing lead exposure, new and
      emerging sources are raising cause for public concern. Recent reports of finding
      lead in eggs from chickens raised in urban gardens has highlighted the need to
      consider the potential health risks of consuming eggs from backyard chickens.
      Following the detection of 0.33 MUg/g lead in the edible portion of eggs
      submitted for lead analysis from a backyard chicken owner, further investigation
      was conducted to determine the source and extent of lead exposure in the flock.
      Several birds, almost two dozen eggs, and environmental samples were submitted to
      the California Animal Health and Food Safety Laboratory for further testing. Lead
      was detected in the blood, liver, kidney, and bone at varying concentrations in
      all birds but was not detected in the muscle tissue. All egg shells contained
      detectable amounts of lead, while only a little over half of the edible portion
      of the eggs contained lead. The detected concentrations in the edible portion
      approached or exceeded the recommended threshold of lead consumption per day that
      should not be exceeded by young children if a child consumed one average-sized
      egg. Peeling paint from a wooded structure adjacent to the flock's coop was the
      likely lead source containing 3,700 MUg/g lead. Thus, removal of the chickens
      from the source and periodic testing of eggs for lead were recommended. This case
      illustrates the need for consumers and health care workers to be aware of
      potential sources for lead exposure such as backyard chickens. 

PMID- 24943226
TI  - Authors' reply to Whitehouse and Fabre.

PMID- 24943232
TI  - Quantifying local and cooperative components in the ferroelectric distortion of
      BaTiO(3): learning from the off-center motion in the MnCl(6)(5-) complex formed
      in KCl:Mn(+).
AB  - The delicate balance between cooperative and local contributions in the
      ferroelectric distortions of BaTiO3 is explored by means of ab initio
      calculations. As a salient feature, it is found that a single Ti(4+) ion in
      BaTiO3 is not allowed to move off-center at ambient pressure, while this is no
      longer true if the lattice is expanded by only ~5%, stressing the high
      sensitivity of the local contribution to chemical and hydrostatic pressures. In
      order to further understand the effect of local contributions on the phase
      transition mechanism of ferroelectrics, we have investigated the surprising C3v 
      > C4v -> Oh local transformations occurring in the 10-50 K temperature range for
      the MnCl6(5-) complex formed in KCl:Mn(+) that mimic the behavior of BaTiO3. From
      Boltzmann analysis of the vibronic levels derived from ab initio calculations and
      considering decoherence introduced by random strains, the present calculations
      reproduce the experimental phase sequence and transition temperatures.
      Furthermore, our calculations show that the off-center instability in KCl:Mn(+)
      would be suppressed by reducing by only 1% the lattice parameter, a situation
      that then becomes comparable to that found for BaTiO3 at ambient pressure. The
      present results thus stress the deep link between the structural phase
      transitions of ferroelectric materials and local phase transitions displayed by
      transition-metal impurities in insulators. 

PMID- 24943228
TI  - The Maristan stigma scale: a standardized international measure of the stigma of
      schizophrenia and other psychoses.
AB  - BACKGROUND: People with schizophrenia face prejudice and discrimination from a
      number of sources including professionals and families. The degree of stigma
      perceived and experienced varies across cultures and communities. We aimed to
      develop a cross-cultural measure of the stigma perceived by people with
      schizophrenia. METHOD: Items for the scale were developed from qualitative group
      interviews with people with schizophrenia in six countries. The scale was then
      applied in face-to-face interviews with 164 participants, 103 of which were
      repeated after 30 days. Principal Axis Factoring and Promax rotation evaluated
      the structure of the scale; Horn's parallel combined with bootstrapping
      determined the number of factors; and intra-class correlation assessed test
      retest reliability. RESULTS: The final scale has 31 items and four factors:
      informal social networks, socio-institutional, health professionals and self
      stigma. Cronbach's alpha was 0.84 for the Factor 1; 0.81 for Factor 2; 0.74 for
      Factor 3, and 0.75 for Factor 4. Correlation matrix among factors revealed that
      most were in the moderate range [0.31-0.49], with the strongest occurring between
      perception of stigma in the informal network and self-stigma and there was also a
      weaker correlation between stigma from health professionals and self-stigma. Test
      retest reliability was highest for informal networks [ICC 0.76 [0.67 -0.83]] and
      self-stigma [ICC 0.74 [0.64-0.81]]. There were no significant differences in the
      scoring due to sex or age. Service users in Argentina had the highest scores in
      almost all dimensions. CONCLUSIONS: The MARISTAN stigma scale is a reliable
      measure of the stigma of schizophrenia and related psychoses across several
      cultures. A confirmatory factor analysis is needed to assess the stability of its
      factor structure.

PMID- 24943233
TI  - Stallion fertility: a focus on the spermatozoon.
AB  - Stallion fertility is a vast subject, with a wide array of permutations that can
      impact reproductive performance in either positive or negative ways. This review
      is intended to address a mere segment of the male fertility issue, but the very
      essence of the male contribution to fertilisation, that of the spermatozoon.
      Spermatozoal ultrastructure and form-to-function are detailed and spermatozoal
      metabolism is discussed, with specific reference to distinctive characteristics
      of stallion spermatozoa. Lastly, methods for assessment of spermatozoal function
      are considered, with emphasis on spermatozoal motility, the acrosome reaction and
      spermatozoon-oocyte interactions. Closing comments address the need for
      development and standardisation of molecular-based assays for use with
      spermatozoa of stallions whose subfertility cannot be explained with conventional
      tests. 

PMID- 24943225
TI  - The high molecular weight glutenin subunit Bx7 allergen from wheat contains
      repetitive IgE epitopes.
AB  - BACKGROUND: Wheat is one of the most common food allergen sources for children
      and adults. The aim of this study was to characterize new wheat allergens using
      an IgE discovery approach and to investigate their IgE epitopes. METHODS: A cDNA
      expression library representing the wheat transcriptome was constructed in phage
      lambda gt11 and screened with IgE antibodies from wheat food allergic patients.
      IgE-reactive cDNA clones coding for portions of high molecular weight (HMW)
      glutenin subunits were identified by sequence analysis of positive clones. IgE
      epitopes were characterized using recombinant fragments from the HMW Bx7 and
      synthetic peptides thereof for testing of allergic patients' sera and in basophil
      degranulation assays. RESULTS: We found that the major IgE-reactive areas of HMW
      glutenins are located in the repetitive regions of the protein and could show
      that two independent IgE-reactive fragments from HMW Bx7 contained repetitive IgE
      epitopes. CONCLUSIONS: Our results demonstrate that IgE antibodies from wheat
      food allergic patients can recognize repetitive epitopes in one of the important
      wheat food allergens. Recombinant HMW Bx7 may be included into the panel of
      allergens for component-resolved diagnosis of wheat food allergy.

PMID- 24943231
TI  - Subretinal tissue plasminogen activator injection to treat submacular haemorrhage
      during age-related macular degeneration.

PMID- 24943229
TI  - Novel use of dexmedetomidine for the treatment of anticholinergic toxidrome.
AB  - INTRODUCTION: We report the case of an adolescent with anticholinergic toxidrome
      from diphenhydramine overdose, whose symptoms were treated with a novel
      application of dexmedetomidine. CASE REPORT: A 13-year-old female developed an
      anticholinergic toxidrome after intentionally ingesting 9.5 mg/kg of
      diphenhydramine. Despite routine supportive therapies, to include appropriate
      doses of lorazepam, she continued to have significant agitation, psychosis, and
      hallucinations. A dexmedetomidine infusion was started to aid in the treatment of
      her agitation and psychosis with marked improvement of her symptoms. DISCUSSION:
      Using dexmedetomidine for the treatment of anticholinergic toxidrome has not been
      previously described in the literature, but there are multiple reports of its use
      in alcohol withdrawal syndrome. We suggest that adding dexmedetomidine as an
      adjunctive agent in the therapy of anticholinergic toxidrome may relieve the
      symptoms of agitation, psychosis, tachycardia, and hypertension, without the
      attendant risk of respiratory depression associated with high doses of
      benzodiazepines.

PMID- 24943234
TI  - Serum zinc concentration is inversely associated with insulin resistance but not
      related with metabolic syndrome in nondiabetic Korean adults.
AB  - Although zinc was known to be associated with insulin metabolism and diabetes,
      the relationship of serum zinc concentration with insulin resistance (IR) and
      metabolic syndrome (MetS) was not well investigated in general population. The
      aim of this study is to evaluate the relationships of serum zinc concentration
      with IR and MetS in a nondiabetic adult population. This cross-sectional study
      included 656 men and 825 women who were nondiabetic adults from the fifth Korea
      National Health and Nutrition Examination Survey conducted in 2010. Serum zinc
      concentration and metabolic parameters were measured. IR was estimated by
      homeostatic model assessment (HOMA2). MetS was defined according to the National
      Cholesterol Education Program Adult Treatment Panel III criteria. Serum zinc
      concentration was negatively correlated with homeostasis model assessment for
      insulin resistance (HOMA2-IR) in men (r = -0.104, P = 0.008), but not in women.
      After adjusting for conventional cardiovascular risk factors, the inverse
      correlation was significant in both men and women (B = -0.262, SE = 0.060 for
      men, and B = -0.129, SE = 0.052 for women). However, serum zinc concentration was
      not different between the groups with and without MetS (P = 0.752 for men and P =
      0.371 for women). In conclusion, serum zinc concentration was inversely
      associated with IR but not related to MetS in nondiabetic adult population.

PMID- 24943236
TI  - Total thyroidectomy is associated with increased risk of complications for low-
      and high-volume surgeons.
AB  - BACKGROUND: There has been an increased use of total thyroidectomy (TT),
      including in the management of benign thyroid diseases. We sought to compare the
      risk of complications between TT and unilateral thyroidectomy (UT) and to
      evaluate the effect of surgeon's experience on outcomes. METHODS: Nationwide
      Inpatient Sample from 2003 to 2009 was used to perform cross-sectional analysis
      of all adult patients who underwent TT and UT for benign or malignant conditions.
      Logistic regression was used to evaluate outcomes and to provide correlation
      between outcome and surgeon volume. Surgeon volume was categorized as low or high
      (performing <10 or >99 thyroid operations/year, respectively). RESULTS: A total
      of 62,722 procedures were included. Most cases were TT (57.9 %) performed for
      benign disease. There was a significantly increased risk of complication after TT
      compared to UT (20.4 vs. 10.8 %: p < 0.0001). High-volume surgeons performed only
      5.0 % of the procedures overall, with 62.6 % of the high-volume surgeon
      procedures being TTs. Low-volume surgeons were more likely to have postoperative
      complications after TT compared to high-volume surgeons (odds ratio 1.53, 95 %
      confidence interval 1.12, 2.11, p = 0.0083). Mean charges were significantly
      higher for TT compared to lobectomy ($19,365 vs. $15,602, p < 0.0001), and length
      of stay was longer for TT compared to lobectomy (1.63 vs. 1.29 days, p < 0.0001).
      CONCLUSIONS: TT is associated with a significantly higher risk of complications
      compared to UT even among high-volume surgeons. Higher surgeon volume is
      associated with improved patient outcomes.

PMID- 24943221
TI  - Metabolic engineering of Salmonella vaccine bacteria to boost human
      Vgamma2Vdelta2 T cell immunity.
AB  - Human Vgamma2Vdelta2 T cells monitor isoprenoid metabolism by recognizing foreign
      (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a metabolite in the 2-C
      methyl-D-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan
      parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate
      pathway used by humans. Whereas microbial infections elicit prolonged expansion
      of memory Vgamma2Vdelta2 T cells, immunization with prenyl pyrophosphates or
      aminobisphosphonates elicit short-term Vgamma2Vdelta2 expansion with rapid anergy
      and deletion upon subsequent immunizations. We hypothesized that a live,
      attenuated bacterial vaccine that overproduces HMBPP would elicit long-lasting
      Vgamma2Vdelta2 T cell immunity by mimicking a natural infection. Therefore, we
      metabolically engineered the avirulent aroA(-) Salmonella enterica serovar
      Typhimurium SL7207 strain by deleting the gene for LytB (the downstream enzyme
      from HMBPP) and functionally complementing for this loss with genes encoding
      mevalonate pathway enzymes. LytB(-) Salmonella SL7207 had high HMBPP levels,
      infected human cells as efficiently as did the wild-type bacteria, and stimulated
      large ex vivo expansions of Vgamma2Vdelta2 T cells from human donors.
      Importantly, vaccination of a rhesus monkey with live lytB(-) Salmonella SL7207
      stimulated a prolonged expansion of Vgamma2Vdelta2 T cells without significant
      side effects or anergy induction. These studies provide proof-of-principle that
      metabolic engineering can be used to derive live bacterial vaccines that boost
      Vgamma2Vdelta2 T cell immunity. Similar engineering of metabolic pathways to
      produce lipid Ags or B vitamin metabolite Ags could be used to derive live
      bacterial vaccine for other unconventional T cells that recognize nonpeptide Ags.

PMID- 24943235
TI  - A safety and feasibility study of an allogeneic colon cancer cell vaccine
      administered with a granulocyte-macrophage colony stimulating factor-producing
      bystander cell line in patients with metastatic colorectal cancer.
AB  - BACKGROUND: Despite recent advances in earlier detection and improvements in
      chemotherapy, the 5-year survival rate of patients with metastatic colorectal
      carcinoma remains poor. Immunotherapy is a potentially effective therapeutic
      approach to the treatment of colorectal carcinoma. Preclinical studies have
      supported the antitumor activity of immunization with a granulocyte-macrophage
      colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine.
      METHODS: A novel colorectal cancer vaccine composed of irradiated, allogeneic
      human colon cancer cells and GM-CSF-producing bystander cells was developed and
      tested in combination with a single intravenous low dose of cyclophosphamide in a
      phase 1 study of patients with metastatic colorectal cancer. RESULTS: A total of
      nine patients were enrolled onto and treated in this study. Six patients had a
      history of colorectal adenocarcinoma hepatic metastases and underwent curative
      metastasectomy, while three other patients had unresectable stage IV disease.
      This study demonstrates the safety and feasibility of this vaccine administered
      in patients with metastatic colorectal cancer. At last follow-up, the six
      patients who underwent curative metastasectomy survived longer than 36 months,
      and four of these six patients were without disease recurrence. Immunologic
      correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances
      the production of anti-MUC1 antibodies. CONCLUSIONS: This vaccine is feasible and
      safe. Future investigation of the efficacy and antitumor immunity of this vaccine
      is warranted.

PMID- 24943237
TI  - Chemoradiotherapy with a radiation boost for anal cancer decreases the risk for
      salvage abdominoperineal resection: analysis from the national cancer data base.
AB  - BACKGROUND: Chemoradiotherapy (CRT), the primary treatment for anal cancer,
      achieves complete tumor regression in most patients. Abdominoperineal resection
      (APR) is reserved for persistent or recurrent disease. An additional boost dose
      of radiation after CRT often is used to improve the response rate for advanced
      local disease (T3, 4, and N+). This study examines the need for salvage APR after
      radiation boost. METHODS: Patients with de novo anal cancer in the National
      Cancer Data Base from the years 2004-2010 were analyzed. Patients with missing
      data points or who did not receive standard CRT were excluded. Variables included
      age, gender, race, primary tumor size, clinical nodal status, TNM stage,
      radiation boost, and APR. A logistic regression model assessing the relationship
      between boost radiation and APR was developed. RESULTS: Of 1,025 patients meeting
      inclusion criteria, 450 patients received CRT without a radiation boost and 575
      patients received CRT with a radiation boost. The two groups were similar in age,
      gender, race, tumor size, nodal status, and TNM stage (p values all >0.05).
      Significant multivariate predictors of salvage APR were tumor size, negative
      nodal status, and boost RT (all p < 0.05), whereas gender, age, race, and TNM
      stage were not significant (all p > 0.05). When controlling for age, tumor size,
      and nodal status, salvage APR is less likely to occur after boost RT (odds ratio
      0.63; 95 % confidence interval 0.47, 0.85; p = 0.003). CONCLUSIONS: When
      controlling for age, tumor size, and nodal status, those who received boost
      radiation for anal cancer were less likely to require salvage APR.

PMID- 24943238
TI  - What's old is new again : editorial about "total thyroidectomy is associated with
      increased risk of complications for low- and high-volume surgeons," by Hauch et
      al., doi:10.1245/s10434-014-3846-8.

PMID- 24943240
TI  - Application of the name Lemna punctata G. Mey., the type of Landoltia Les & D. J.
      Crawford.
AB  - A recent (2011) attempt to change the previously designated type of the name of a
      duckweed species is discussed. Lemna punctata was first applied by Meyer in 1818
      to a plant collected from South America, but original specimens have not been
      located. A prior neotype designation associated this name with a species native
      to parts of Asia, Australia and the Pacific, and widely introduced elsewhere,
      including South America. The species is generally treated by taxonomists in the
      genus Spirodela (either as S. punctata or the synonym S. oligorrhiza) or, more
      recently, as the sole member of the new (1999) genus Landoltia (as L. punctata).
      If accepted, this 2011 attempt to re-neotypify L. punctata would disrupt the
      names of two duckweed species as well as that of Landoltia. Nomenclatural
      arguments against accepting this new typification are provided, thereby
      supporting the continued usage of Landoltia in the sense intended by its original
      authors.

PMID- 24943239
TI  - Rituximab with or without a conventional maintenance agent in the treatment of
      relapsing granulomatosis with polyangiitis (Wegener's): a retrospective single
      center study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of rituximab (RTX) induction
      therapy and the duration of remission, when RTX is used with or without a
      conventional maintenance agent, in a cohort of patients with granulomatosis with
      polyangiitis (Wegener's) (GPA). METHODS: This was a retrospective, single-center
      study of patients with relapsing GPA treated with at least 1 course of RTX (4
      weekly doses of 375 mg/m(2) intravenously [IV] or 2 fixed doses of 1,000 mg IV 2
      weeks apart). Complete remission was defined as the absence of disease activity
      measured by a Birmingham Vasculitis Activity Score for Wegener's granulomatosis
      of 0 and not qualified by the prednisone dosage at the time. RESULTS: Eighty-nine
      patients achieved remission after their first course of RTX and were not re
      treated preemptively with RTX to maintain remission of their disease during
      followup. Among these patients, relapse-free survival was significantly higher in
      those who received a conventional maintenance agent (azathioprine, methotrexate,
      or mycophenolate mofetil) in conjunction with RTX and glucocorticoids (n = 47)
      than in those who received no additional immunosuppressive agent (n = 42) (P =
      0.04). The hazard ratio of relapse in those receiving a maintenance agent was
      0.53 (95% confidence interval 0.29-0.97). Serious adverse events did not differ
      between the 2 groups. Within a subset of 15 patients in the cohort who were
      relapse free 2 years after 1 course of RTX, remissions endured for 2-6 years in 8
      patients. CONCLUSION: RTX is an effective remission-inducing agent in GPA. The
      addition of a conventional maintenance agent to RTX and glucocorticoids decreased
      the incidence of relapse and did not result in a higher incidence of adverse
      events.

PMID- 24943241
TI  - Comparison of the adipogenesis in intramuscular and subcutaneous adipocytes from
      Bamei and Landrace pigs.
AB  - Fat deposition is a complex process involving proliferation, differentiation, and
      lipogenesis of adipocytes. Bamei and Landrace are considered to represent fat-
      and lean-type pig breeds. Subcutaneous (SC) and intramuscular (IM) pre-adipocytes
      were cultured to compare the proliferation and lipogenesis in these breeds. The
      differentiated adipocytes were exposed to glucose or insulin to evaluate their
      effects on lipogenesis and lipogenic gene expression. Pre-adipocytes proliferated
      dramatically faster in SC vs. IM cells, and in Bamei vs. Landrace breeds.
      Lipogenesis and lipogenic gene expression had a greater increase in Bamei than in
      Landrace, and in SC vs. IM in the process of differentiation. Glucose markedly
      promoted lipogenesis and lipogenic gene expression in differentiated adipocytes.
      The stimulation of high-glucose levels on lipogenesis and ChREBP and lipogenic
      gene expression was higher in SC than IM adipocytes, and in Bamei vs. Landrace.
      Insulin largely increased SREBP-1c expression, however it modestly stimulated
      lipogenesis and lipogenic gene expression, and there was no difference between
      cell populationsor between breeds. These data demonstrated that regional and
      varietal differences obviously existed in the development of porcine adipocytes.
      The proliferation and differentiation capacity of pre-adipocytes, and the
      adipocyte lipogenesis stimulated by glucose, are stronger in Bamei than Landrace,
      and in SC vs. IM adipocytes independent of breed. 

PMID- 24943243
TI  - Synthesis, protonation equilibrium and peculiar thermal decomposition behavior of
      cyclo-tri-MU-imidotetraphosphate.
AB  - The synthesis and isolation of the sodium salt of cyclo-tri-MU
      imidotetraphosphate, i.e. Na4cP4O9(NH)3.H2O, were achieved by the hydrolysis of
      Na4cP4O8(NH)4.2H2O under very weak acidic conditions, i.e. using 0.2 mol L(-1)
      propionic acid and the pH-controlled recrystallization procedure. The purity of
      Na4cP4O9(NH)3.H2O was improved from 2% to 95% by the pH-controlled
      recrystallization only two times. The first protonation constants of a series of
      cyclo-MU-imidotetraphosphate anions, i.e. cP4O(12-n)(NH)n(4-) (n = 0, 2, 3, 4),
      were determined by potentiometric titration and (31)P NMR chemical shift
      measurements in aqueous solution. Regardless of the paucity of the purity of
      trans-cP4O10(NH)2(4-) anions, the protonation processes of all anions may be
      evaluated accurately without any previous purification, because the NMR signals
      corresponding to cP4O(12-n)(NH)n(4-) (n = 0, 2, 3, 4) anions are well resolved.
      The logarithmic first protonation constants increase with a "linear" increase in
      the number of imino groups which constitute the ligand molecules. Macroscopic
      protonation reactions could be divided into three microscopic protonation
      processes for -O-PO2-O-, -O-PO2-NH-, and -NH-PO2-NH- groups. The basicity of the 
      NH-PO2-NH- group is especially high, because the delocalization of H(+) ions by
      lactam-lactim tautomerism on the whole ring molecule of cP3O6(NH)3 and cP4O8(NH)4
      enhances the protonation of these ligands. In addition, also the concurrent
      change observed in the (31)P NMR chemical shift values of the phosphorus nuclei
      in the -O-PO2-NH- and -NH-PO2-NH- groups of cP4O9(NH)3(4-) anions suggested the
      effect of the lactam-lactim tautomerism. The intrinsic (31)P NMR chemical shifts
      for the central phosphorus nuclei for -O-PO2-O-, -O-PO2-NH-, and -NH-PO2-NH-
      groups show a good proportional relationship with the number of nitrogen atoms
      bonded to the central phosphorus atoms. Two types of imino groups with mutually
      dissimilar chemical environments which are present in the Na4cP4O9(NH)3 molecule,
      that is -O-PO2-NH-PO2-NH- and -NH-PO2-NH-PO2-NH-, brought about a two-stage
      pyrolytic elimination of imino groups from the initial stage of combustion over a
      wide temperature range.

PMID- 24943242
TI  - Glucose-sensitive QCM-sensors via direct surface RAFT polymerization.
AB  - Thin, phenylboronic acid-containing polymer coatings are potentially attractive
      sensory layers for a range of glucose monitoring systems. This contribution
      presents the synthesis and properties of glucose-sensitive polymer brushes
      obtained via surface RAFT polymerization of 3-methacrylamido phenylboronic acid
      (MAPBA). This synthetic strategy is attractive since it allows the controlled
      growth of PMAPBA brushes with film thicknesses of up to 20 nm via direct
      polymerization of MAPBA without the need for additional post-polymerization
      modification or deprotection steps. QCM-D sensor chips modified with a PMAPBA
      layer respond with a linear change in the shift of the fundamental resonance
      frequency over a range of physiologically relevant glucose concentrations and are
      insensitive toward the presence of fructose, thus validating the potential of
      these polymer brush films as glucose sensory thin coatings. 

PMID- 24943245
TI  - Single-ring ablation compared with standard circumferential pulmonary vein
      isolation using remote magnetic catheter navigation.
AB  - PURPOSE: In ablation of atrial fibrillation, the single-ring method aims for
      isolation of the posterior wall of the left atrium (LA) including the pulmonary
      veins (PVs) but avoiding posterior LA lesions. The aim of this randomized
      prospective study was to evaluate safety and efficacy of remote magnetic
      navigation (RMN)-guided single-ring ablation strategy as compared to standard RMN
      guided circumferential PV ablation (PVA). METHODS: Eighty consecutive patients
      undergoing PVA were enrolled prospectively and randomized equally into two study
      groups. RMN using the Stereotaxis system and open-irrigated 3.5-mm ablation
      catheters were used with a 3D mapping system in all procedures. Forty patients
      underwent RMN-guided single-ring ablation, and 40 patients received RMN-guided
      circumferential PVA. RESULTS: In the circumferential group, 3.3 +/- 1.1 PVs were
      successfully isolated at the end of the procedure as compared to 3.1 +/- 1.3 in
      the single-ring (box) group (p=0.38). All patients in the box group required
      additional posterior lesions in order to achieve electrical isolation of the PVs.
      Single-ring ablation was associated with longer procedure duration (p=0.01) and
      ablation time (p=0.001). After a single procedure, the proportion of patients
      free of any atrial tachycardia (AT)/atrial fibrillation (AF) episode at 12-month
      follow-up was 57 % in the box group and 58 % in the circ group. Using RMN, only
      minor complications have been observed. CONCLUSIONS: RMN-guided single-ring PVA
      provides comparable acute and long-term success rates as compared to RMN-guided
      circumferential PVA but requires additional posterior lesions to achieve PV
      isolation and increased procedure and ablation time. Procedural complication
      rates are low when using RMN.

PMID- 24943244
TI  - OmpU as a biomarker for rapid discrimination between toxigenic and epidemic
      Vibrio cholerae O1/O139 and non-epidemic Vibrio cholerae in a modified MALDI-TOF
      MS assay.
AB  - BACKGROUND: Cholera is an acute diarrheal disease caused by Vibrio cholerae.
      Outbreaks are caused by a genetically homogenous group of strains from serogroup
      O1 or O139 that are able to produce the cholera toxin. Rapid detection and
      identification of these epidemic strains is essential for an effective response
      to cholera outbreaks. RESULTS: The use of ferulic acid as a matrix in a new MALDI
      TOF MS assay increased the measurable mass range of existing MALDI-TOF MS
      protocols for bacterial identification. The assay enabled rapid discrimination
      between epidemic V. cholerae O1/O139 strains and other less pathogenic V.
      cholerae strains. OmpU, an outer membrane protein whose amino acid sequence is
      highly conserved among epidemic strains of V. cholerae, appeared as a
      discriminatory marker in the novel MALDI-TOF MS assay. CONCLUSIONS: The extended
      mass range of MALDI-TOF MS measurements obtained by using ferulic acid improved
      the screening for biomarkers in complex protein mixtures. Differences in the mass
      of abundant homologous proteins due to variation in amino acid sequences can
      rapidly be examined in multiple samples. Here, a rapid MALDI-TOF MS assay was
      developed that could discriminate between epidemic O1/O139 strains and other less
      pathogenic V. cholerae strains based on differences in mass of the OmpU protein.
      It appeared that the amino acid sequence of OmpU from epidemic V. cholerae
      O1/O139 strains is unique and highly conserved.

PMID- 24943246
TI  - Low molecular weight protamine (LMWP): a nontoxic protamine substitute and an
      effective cell-penetrating peptide.
AB  - Low molecular weight protamine (LMWP) is a peptide fragment produced in our
      laboratory from enzymatic digestion of native protamine. More than 30 papers
      studying the properties and applications of LMWP have been published by our group
      in various journals since its initial discovery in 1999. Results have shown that
      LMWP could completely neutralize the anticoagulant functions of both heparin and
      low molecular weight heparin (LMWH), with reduced antigenicity and cross
      reactivity toward the mice-derived anti-protamine antibodies. Aside from its
      potential as a heparin/LMWH antagonist, LMWP also shows the ability to retard
      insulin adsorption by the formation of an insoluble complex, making it a less
      toxic long-lasting insulin product than the conventional neutral protamine
      Hagedorn (NPH) insulin for diabetic control. Importantly, LMWP (Sequence:
      VSRRRRRRGGRRRR), with 10 arginine residues in its structure, could function as a
      cell-penetrating peptide (CPP), also termed protein transduction domain (PTD), to
      achieve effective intracellular protein or gene delivery in clinical practice. In
      this paper, we present a thorough review of our work related to LMWP, with the
      aim of providing readers an insight into its potential to be a clinical protamine
      substitute as well as a non-toxic cell penetrating peptide applicable to achieve
      intracellular protein and gene delivery. 

PMID- 24943247
TI  - Breeding programs for smallholder sheep farming systems: I. Evaluation of
      alternative designs of breeding schemes.
AB  - Village- and central nucleus-based schemes were simulated and evaluated for their
      relative bio-economic efficiencies, using Ethiopia's Menz sheep as example. The
      schemes were: village-based 2-tier (Scheme-1) and 1-tier (Scheme-2) cooperative
      village breeding schemes, dispersed village-based nuclei scheme (Scheme-3),
      conventional 2-tier central nucleus-based scheme (Scheme-4), and schemes linking
      a central nucleus and village multiplier nuclei with selection in central nucleus
      (Scheme-5) or in both central and village nuclei (Scheme-6). Among village-based
      schemes, Scheme-1 gave the highest genetic progress, while Scheme-2 was
      economically the most efficient with genetic gain in the breeding objective of
      Birr 5.6 and a profit of Birr 37.2/ewe/year. The central nucleus schemes were
      more efficient than the village schemes. Scheme-4 was the most efficient with
      genetic gain in the breeding objective of Birr 13.5 and a profit of Birr 71.2,
      but is operationally more difficult as it requires a very large central nucleus.
      The choice between village and central nucleus-based schemes would depend on
      local conditions (availability of infrastructure, logistics and technical knowhow
      and support). Linking central nucleus with village-based nuclei (Scheme-6) would
      be a feasible option to overcome the operational difficulties of the conventional
      central nucleus scheme. If a village-based breeding program is envisaged as
      should be the 1st step in most low-input systems, then Scheme-2 is the most
      efficient. To scale out to an entire Menz breed level, Scheme-3 would be
      recommended. 

PMID- 24943248
TI  - Stress response of Pseudomonas species to silver nanoparticles at the molecular
      level.
AB  - In recent years, silver nanoparticles (AgNPs) have been shown to possess broad
      antibacterial activity. The present study investigated the cytotoxicity of AgNPs
      to a common soil bacterium, Pseudomonas sp. The molecular mechanism involved in
      its stress response to AgNPs was also studied. The minimum inhibitory
      concentration (MIC) of AgNPs was found to be 0.2 mg/L. At a sublethal
      concentration of 0.1 mg/L AgNPs, the protein expression profile of Pseudomonas
      showed overexpression of stress proteins such as ribosomal proteins S2 and L9,
      alkyl hydroperoxide reductase/thiol-specific antioxidant (AhpC/TSA) family
      protein, and keto-hydroxyglutarate aldolase (KHGA). The upregulation of these
      proteins was further confirmed by quantitative polymerase chain reaction. The
      results showed increased expression of ribosomal protein S2, KHGA, AhpC/TSA, and
      ribosomal protein L9 by 1.09-, 3.41-, 1.52-, and 1.56-fold, respectively (p <
      0.05), after AgNP exposure compared with control. The present study clearly
      demonstrates that AgNPs are toxic to soil bacteria and induce oxidative and
      metabolic stress.

PMID- 24943249
TI  - Characterization of a new cry2Ab gene of Bacillus thuringiensis with high
      insecticidal activity against Plutella xylostella L.
AB  - Bacillus thuringiensis (Bt) strain FJAT-12 was a novel Bt strain isolated by
      Agricultural Bio-Resources Institute, Fujian Academy of Agricultural Science. In
      this study, a new cry2Ab gene was cloned from Bt strain FJAT-12 and named as
      cry2Ab30 by Bt delta-endotoxin Nomenclature Committee. The sequencing results
      showed there were two mutations in conservative sites which led to two amino
      acids modification. Homology modeling indicated that the two changes were located
      in beta-sheet of Domain II. A prokaryotic expression vector pET30a-cry2Ab30 was
      constructed and the expressed protein was analyzed by western blot using Cry2Ab
      antibody. The expression conditions including IPTG concentration, revolution and
      temperature were optimized to get the highest expression level by SDS-PAGE and
      BandScan. The bioassay results also showed that the Cry2Ab30 toxin had high
      insecticidal activity against Plutella xylostella and the LC50 value was 0.0103
      MUg.mL(-1). The two mutations in beta-sheet of Domain II might contribute to
      insecticidal activity of Cry2Ab30 toxin against Plutella xylostella.

PMID- 24943250
TI  - Vitamin D insufficiency among hospitalised children in the Northern Territory.
AB  - AIM: Acute lower respiratory infections (ALRIs) are the most common reason for
      hospitalisation of young children in the Northern Territory of Australia.
      International studies have linked vitamin D deficiency with increased risk of
      ALRI in paediatric populations, but this has not been explored in tropical
      regions such as the Top End of the Northern Territory. The aim of this study is
      to determine the prevalence of vitamin D insufficiency among children
      hospitalised with ALRI in the Northern Territory. METHODS: Vitamin D serum
      metabolite (25OHD3) levels were retrospectively measured using liquid
      chromatography-mass spectrometry in 74 children (64% male; 57% Indigenous) aged
      less than 3 years admitted to Royal Darwin Hospital in the Northern Territory of
      Australia between May 2008 and May 2010. RESULTS: There were 44 (59%) ALRI
      classified hospitalisations and 30 (41%) non-ALRI-classified hospitalisations.
      The most common ALRI diagnoses were bronchiolitis (n = 22, 30%) and pneumonia (n
      = 21, 28%), whereas the most common non-ALRI diagnosis was gastroenteritis (n =
      20, 27%). Overall, 24/74 (32%) children had 25OHD3 levels <75 nmol/L
      (insufficiency). For children hospitalised with ALRI, 23% (10/44) had vitamin D
      insufficiency compared with 47% (14/30) among children hospitalised for other
      reasons (odds ratio 0.34, 95% confidence interval 0.11-1.03; P = 0.043). Twelve
      of the 20 (60%) children hospitalised for gastroenteritis had vitamin D
      insufficiency. CONCLUSIONS: Vitamin D insufficiency was observed in almost one
      third of these hospitalised children. Children hospitalised with an ALRI were
      less likely to have vitamin D insufficiency compared with children hospitalised
      for other conditions (predominantly gastroenteritis).

PMID- 24943252
TI  - Optimizing image quality for pediatric torso computed tomography: the use of
      advanced iterative reconstruction and wide-detector scanning techniques.
AB  - OBJECTIVES: To compare radiation exposure and image quality in children
      undergoing torso helical acquisition computed tomography (CT) using filtered back
      projection (FBP) or adaptive iterative dose reduction (AIDR) 3D reconstruction
      algorithms. A secondary purpose is to compare radiation exposure and image
      quality in children undergoing torso CT acquired with helical or wide-detector
      techniques reconstructed with AIDR 3D. METHODS: The study was approved by the
      institutional review board. Phase 1 included 200 helical torso CT studies: 100
      using FBP and 100 using AIDR 3D. The size-specific dose estimate (SSDE) was
      calculated for each study. Region of interest (ROI) noise measurements were
      recorded in the thorax, abdomen, and pelvis for each study. Unpaired t tests
      compared SSDE and image noise for each group. Phase 2 included 100 wide-detector
      CT torso studies using AIDR 3D. Size-specific dose estimate and ROI noise
      measurements were calculated. Unpaired t tests compared helical and wide-detector
      SSDE and ROI. Additional t tests looked for age- and weight-specific differences
      in the helical and wide-detector groups. RESULTS: Phase 1: AIDR 3D showed
      significant reduction in SSDE (P = 0.0001) and significant improvement in image
      quality. Phase 2: no significant difference in SSDE was observed. Children
      younger than 6 years had a significant reduction in SSDE with wide-detector
      technique (P = 0.0445) with no loss in image quality. CONCLUSIONS: Adaptive
      iterative dose reduction 3D produces significant reduction in radiation dose
      without degradation to image quality compared with FBP. Significant dose
      reduction without loss of image quality can also be obtained in younger, smaller
      children using wide-detector technique.

PMID- 24943251
TI  - Assessment of dynamic contrast-enhanced magnetic resonance imaging in the
      differentiation of pancreatic ductal adenocarcinoma from other pancreatic solid
      lesions.
AB  - PURPOSE: The purpose of this study was to investigate the diagnostic value of
      quantitative dynamic contrast-enhanced magnetic resonance imaging (QDCE-MRI) of
      pancreatic ductal adenocarcinoma (PDA) on a 3.0-T magnetic resonance. MATERIALS
      AND METHODS: The study was approved by the local institutional review board, and
      all subjects provided written informed consent. Seventy-five patients with
      suspected pancreatic tumors underwent QDCE-MRI, in which 33 patients with cases
      of pancreatic solid lesions (23 patients with PDA, 3 patients with solid
      pseudopapillary tumor, 3 patients with neuroendocrine tumor, 2 patients with mass
      forming pancreatitis, 2 patients with ampullary adenocarcinoma) proven through
      histopathologic diagnosis were included in this study. The parameters of QDCE-MRI
      were recorded and compared. RESULTS: The parameters of QDCE-MRI of PDA tissue and
      non-cancer tissue did not show significant difference between 2-compartment model
      (2C) and 3-compartment model (3C). The contrast enhancement ratio of non-cancer
      tissue with dilatation of pancreatic duct was significantly higher than that of
      non-cancer tissue without dilatation of pancreatic duct, whereas the rate
      constant (Kep) of 2C was significantly lower. The maximun slope of signal
      intensity ascent (MxSIp), the volume transfer constant (Ktrans), and the Kep of
      PDA tissue were significantly lower than those of the non-cancer tissue, but the
      time of peaking of contrast agent (PeakT) was significantly longer. Receiver
      operating characteristic curves showed that the areas under the curve of
      differentiating PDA tissue from the non-cancer tissue were 0.82, 0.79, 0.91,
      0.94, 0.88, and 0.89 for PeakT, MxSIp, Ktrans-2C, Kep-2C, Ktrans-3C, and Kep-3C,
      respectively. The PDA tissue showed lower MxSIp and Kep as well as longer PeakT
      than those of the non-PDA lesions. The receiver operating characteristic curves
      showed that the areas under the curve of differentiating the PDA from the non-PDA
      tumor were 0.73, 0.72, 0.79, and 0.72 for PeakT, MxSIp, Kep-2C, and Kep-3C,
      respectively CONCLUSIONS: The parameters of QDCE-MRI are useful for the diagnosis
      of PDA.

PMID- 24943253
TI  - In vivo evaluation of sciatic nerve crush injury using diffusion tensor imaging:
      correlation with nerve function and histology.
AB  - OBJECTIVE: The aim of this study was to prospectively estimate magnetic resonance
      diffusion tensor imaging parameters in distal portions of crushed sciatic nerves
      in rabbits and correlation with neurological function and histology. METHODS:
      Thirty-two rabbits were randomly divided into 8 groups and followed up at 10
      weeks. The right sciatic nerves were crushed, and the left sciatic nerves served
      as the control group with sham operation. Another 4 rabbits were chosen in the
      normal control group. Diffusion tensor imaging scan was obtained on bilateral
      sciatic nerves using spin-echo single-shot echo planar imaging. The values of
      fractional anisotropy (FA), apparent diffusion coefficient, and eigenvalue
      (lambda? and lambda?) were measured on diffusion tensor imaging. Quantitative
      assessment of functional recovery in crushed nerves included toe-spreading reflex
      and modified Tarlov score, as well as pathology of the injured nerves. RESULTS:
      Fractional anisotropy of distal portions in injured nerves reduced slightly on
      the first day and dropped to the minimum at the fourth day after surgery. Then,
      FA increased gradually from the eighth day to the eighth week. After that, FA
      recovered nearly normal in the 10th week after injury. There was statistical
      significance in FA during 4 days to the eighth week and lambda? values between
      distal portions of injured nerves and normal control nerves (P < 0.05).
      Fractional anisotropy of distal portions to injured nerves correlated
      significantly with the nerve function score(r = 0.898, P < 0.01), whereas lambda?
      of distal portions of injured nerves demonstrated negative correlation with the
      nerve function score(r = -0.820, <0.01). Fractional anisotropy values of distal
      portions of injured nerves formed a similar time course as functional recovery,
      whereas lambda? indicated a opposite trend. CONCLUSIONS: The changes in FA and
      lambda? of distal portions of injured sciatic nerves correlate well with
      functional recovery and histology. Therefore, FA and lambda? of distal portions
      of injured sciatic nerves can be used as a marker to monitor Wallerian
      degeneration and regeneration of crushed sciatic nerves.

PMID- 24943255
TI  - Isolated pelvic fluid in males on outpatient magnetic resonance imaging
      examinations: differences in incidence based on age.
AB  - PURPOSE: Determine the incidence and amount of isolated pelvic fluid in males,
      stratified by age, on outpatient pelvic magnetic resonance imaging (MRI)
      examinations performed for lower back or extremity pain. METHODS: After
      institutional review board approval, 161 pelvic MRIs performed on males for
      musculoskeletal or neurologic indications over an 18-month period were
      retrospectively reviewed for isolated pelvic fluid by 2 radiologists. Patients
      with a potential etiology for the fluid were excluded. Volume and maximal 2
      dimensional measurements of fluid were calculated. Statistical analysis included
      logistic regression, Wilcoxon rank-sum, and chi tests. RESULTS: Twenty (44.4%) of
      45 patients 5 to 29 years old, 5 (10%) of 50 patients 30 to 49 years old, and 4
      (6.1%) of 66 patients older than 50 years had isolated pelvic fluid (P < 0.001).
      Mean volume of fluid was 2.5 mL; 97% (28/29) had less than 10 mL. Mean maximal 2
      dimensional measurement was 2.1 cm; 93% (27/29) had less than 6 cm(2).
      CONCLUSIONS: Isolated fluid is greater than 7 times more common on outpatient
      pelvic MRIs in males younger than 30 years compared with men older than 49 years.
      Fluid rarely exceeded 10 mL or 6 cm(2).

PMID- 24943254
TI  - Influence of smoking history on imaging characteristics among patients with human
      papillomavirus-positive oropharyngeal cancer: a blinded matched-pair analysis.
AB  - BACKGROUND AND PURPOSE: Human papillomavirus (HPV)-positive oropharyngeal cancers
      represent a distinct clinical entity with more favorable prognosis than do HPV
      negative oropharyngeal cancers. However, among patients with HPV-positive
      oropharyngeal carcinomas, those with a significant smoking history have a much
      worse prognosis. Recently, imaging characteristics of oropharyngeal cancers were
      identified as markers of poor prognosis. The purpose of this study was to
      determine whether nodal imaging characteristics differ between smokers and
      never/light smokers with HPV-positive oropharyngeal cancer. MATERIALS AND
      METHODS: A review of 130 pretreatment computed tomographic examinations of HPV
      positive oropharyngeal cancers in smokers (>10 pack-years) and never/light
      smokers (10 pack-years) matched for T stage and tumor subsite was performed, with
      the reviewing radiologist blinded to the HPV status, smoking history, and
      clinical stage. Additionally 24 pretreatment computed tomographic examinations of
      patients with HPV-negative oropharyngeal cancers were also reviewed in a blinded
      fashion. Imaging characteristics of metastatic nodal disease were compared using
      the testing (Fisher exact testing where appropriate) and McNemar testing for the
      matched-pair analysis. RESULTS: As expected, those with HPV-positive
      oropharyngeal cancer were more likely to be younger, male, non-Hispanic white,
      never/former smokers, and never drinkers than were those with HPV-negative
      oropharyngeal cancer. Furthermore, the HPV-positive oropharyngeal cancers were
      more likely to be in the tonsil, smaller T category, higher N category, poorly
      differentiated, than were the HPV-negative oropharyngeal cancers. However, among
      the HPV-positive oropharyngeal cancers, we could identify no obvious difference
      in the pretreatment imaging characteristics of paired smokers and never/light
      smokers. CONCLUSIONS: Among the patients with HPV-positive oropharyngeal cancer,
      no imaging characteristics were identified to correlate with the critical
      prognostic feature smoking status. Cystic and necrotic nodal metastases, as
      described previously, were more common among the patients with HPV-positive than
      those with HPV-negative oropharyngeal cancers. Although cystic nodal metastases
      were more common among the never/light smokers with HPV-positive oropharyngeal
      cancer than among smokers with HPV-positive oropharyngeal cancer, however,
      because these results did not reach statistical significance, we concluded that
      the imaging results cannot serve as a surrogate for an HPV-driven phenotype.

PMID- 24943257
TI  - Production of scopularide A in submerged culture with Scopulariopsis brevicaulis.
AB  - BACKGROUND: Marine organisms produce many novel compounds with useful biological
      activity, but are currently underexploited. Considerable research has been
      invested in the study of compounds from marine bacteria, and several groups have
      now recognised that marine fungi also produce an interesting range of compounds.
      During product discovery, these compounds are often produced only in non-agitated
      culture conditions, which are unfortunately not well suited for scaling up. A
      marine isolate of Scopulariopsis brevicaulis, strain LF580, produces the
      cyclodepsipeptide scopularide A, which has previously only been produced in non
      agitated cultivation. RESULTS: Scopulariopsis brevicaulis LF580 produced
      scopularide A when grown in batch and fed-batch submerged cultures. Scopularide A
      was extracted primarily from the biomass, with approximately 7% being extractable
      from the culture supernatant. By increasing the biomass density of the
      cultivations, we were able to increase the volumetric production of the cultures,
      but it was important to avoid nitrogen limitation. Specific production also
      increased with increasing biomass density, leading to improvements in volumetric
      production up to 29-fold, compared with previous, non-agitated cultivations. Cell
      densities up to 36 g L-1 were achieved in 1 to 10 L bioreactors. Production of
      scopularide A was optimised in complex medium, but was also possible in a
      completely defined medium. CONCLUSIONS: Scopularide A production has been
      transferred from a non-agitated to a stirred tank bioreactor environment with an
      approximately 6-fold increase in specific and 29-fold increase in volumetric
      production. Production of scopularide A in stirred tank bioreactors demonstrates
      that marine fungal compounds can be suitable for scalable production, even with
      the native production organism.

PMID- 24943259
TI  - Reducing false positive diagnoses in mild cognitive impairment: the importance of
      comprehensive neuropsychological assessment.
AB  - BACKGROUND AND PURPOSE: Longitudinal studies of mild cognitive impairment (MCI)
      report that a sizeable proportion of MCI cases revert to normal levels of
      functioning over time. The rate of recovery from MCI indicates that existing MCI
      diagnostic criteria result in an unacceptably high rate of false positive
      diagnoses and lack adequate sensitivity and specificity. METHODS: The aim of the
      present study was to identify a set of neuropsychological measures able to
      differentiate between true positive cases of MCI from those who were unimpaired
      at 11 months' follow-up. RESULTS: A discriminant function analysis identified
      that a combination of measures of complex sustained attention, semantic memory,
      working memory, episodic memory and selective attention correctly classified
      outcome in more than 80% of cases. The rate of false positive diagnoses (5.93%)
      was considerably lower than is evident in previously published MCI studies.
      CONCLUSIONS: The results of the present study indicate that the rate of false
      positive MCI diagnoses can be significantly reduced through the use of sensitive
      and specific neuropsychological measures of memory and non-memory functions.

PMID- 24943256
TI  - (4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a novel
      inhibitor of autophagy.
AB  - BACKGROUND AND PURPOSE: Autophagy is an important intracellular degradation
      system, which is related to various diseases. In preliminary experiments we found
      that D4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline (DMH1)
      inhibited autophagy responses. However DMH1 also inhibits the signalling pathway
      activated by bone morphogenetic protein-4 (BMP4). The aim of the present study
      was to elucidate the inhibitory effects of DMH1 on autophagy and the underlying
      mechanisms. EXPERIMENTAL APPROACH: The effects of DMH1 on autophagy responses
      were evaluated in cultures of different cell types and with different stimuli to
      induce autophagy, using Western blots, transmission electron microscopy and
      fluorescent microscopy. KEY RESULTS: DMH1 inhibited starvation-induced autophagy
      in cardiomyocytes, HeLa and MCF-7 cells, without involving the signalling pathway
      of BMP4. DMH1 inhibited aminoimidazole carboxamide ribonucleotide (AICAR)- and
      rapamycin-induced autophagy in HeLa and MCF-7 cells. DMH1 reversed starvation-
      and AICAR-induced inhibition of Akt, mammalian target of rapamycin (mTOR) and
      p70S6 kinase (S6K), and reversed rapamycin-induced inhibition of mTOR and S6K.
      DMH1 reversed starvation-induced decrease of the phosphorylated form of glycogen
      synthase kinase-3 in MCF-7 and HT29 cells. Activation of Akt and inhibition of
      autophagy induced by DMH1 were antagonized by an Akt specific inhibitor or by
      small interfering RNA for Akt in HeLa cells. CONCLUSION AND IMPLICATIONS: DMH1
      inhibited cellular autophagy responses in a range of cell types and the
      underlying mechanisms include activation of the Akt pathway.

PMID- 24943258
TI  - Role of the disaggregase ClpB in processing of proteins aggregated as inclusion
      bodies.
AB  - Overproduction of heterologous proteins in bacterial systems often results in the
      formation of insoluble inclusion bodies (IBs), which is a major impediment in
      biochemical research and biotechnology. In principle, the activity of molecular
      chaperones could be employed to gain control over the IB formation and to improve
      the recombinant protein yields, but the potential of each of the major bacterial
      chaperones (DnaK/J, GroEL/ES, and ClpB) to process IBs has not been fully
      established yet. We investigated the formation of inclusion bodies (IBs) of two
      aggregation-prone proteins, VP1LAC and VP1GFP, overproduced in Escherichiacoli in
      the presence and absence of the chaperone ClpB. We found that both ClpB isoforms,
      ClpB95 and ClpB80 accumulated in E. coli cells during the production of IBs. The
      amount of IB proteins increased in the absence of ClpB. ClpB supported the
      resolubilization and reactivation of the aggregated VP1LAC and VP1GFP in E. coli
      cells. The IB disaggregation was optimal in the presence of both ClpB95 and
      ClpB80. Our results indicate an essential role of ClpB in controlling protein
      aggregation and inclusion body formation in bacteria. 

PMID- 24943260
TI  - Intra-abdominal metastatic melanoma presenting as intussusception.

PMID- 24943261
TI  - Lack of anti-factor Xa assay standardization results in significant low molecular
      weight heparin (enoxaparin) dose variation in neonates and children.
AB  - INTRODUCTION: Enoxaparin is a frequently used anticoagulant in children. Unlike
      in adults, consensus guidelines recommend therapeutic monitoring to a target anti
      factor Xa level of 0.5-1 U mL(-1) . Therapeutic ranges are not well correlated
      with clinical outcomes (e.g. thrombosis or hemorrhage), and assays are not
      standardized. Owing to limited reagent supplies, our clinical laboratory
      conducted a validation process and switched anti-FXa assays. Although the assays
      correlated well with each other, anti-FXa values were, on average, 33% higher
      with the new assay. The target anti-FXa range was not altered. We evaluated how
      this change in anti-FXa assays influenced enoxaparin dosing (mg kg(-1) ).
      METHODS: Enoxaparin dosing and anti-FXa values for all patients started on
      enoxaparin for the 6 months before and after assay change were retrospectively
      compiled and analyzed with a Student's t-test. RESULTS: One hundred and nine
      children were started on enoxaparin before assay change, and 104 after assay
      change. The mean therapeutic enoxaparin dose (mg kg(-1) ) was significantly lower
      in subjects aged < 3 months (P = 0.01) and 3 months to 2 years (P < 0.0001), but
      not in subjects aged > 2 years (P = 0.18), after assay change. The median number
      of enoxaparin dose changes required to achieve the target range was significantly
      reduced after assay change, from 1 to 0 (P = 0.004). CONCLUSIONS: The current
      pediatric practice of dose adjustment to achieve and maintain a target anti-FXa
      range is vulnerable to assay determination, which may provide false reassurance
      of efficacy and safety and represent misappropriation of time and resources.
      These data support a pediatric randomized controlled clinical trial comparing the
      safety and efficacy of enoxaparin weight-based dosing with or without dose
      titration based on anti-FXa.

PMID- 24943262
TI  - Developing a reference of normal lung sounds in healthy Peruvian children.
AB  - PURPOSE: Lung auscultation has long been a standard of care for the diagnosis of
      respiratory diseases. Recent advances in electronic auscultation and signal
      processing have yet to find clinical acceptance; however, computerized lung sound
      analysis may be ideal for pediatric populations in settings, where skilled
      healthcare providers are commonly unavailable. We described features of normal
      lung sounds in young children using a novel signal processing approach to lay a
      foundation for identifying pathologic respiratory sounds. METHODS: 186 healthy
      children with normal pulmonary exams and without respiratory complaints were
      enrolled at a tertiary care hospital in Lima, Peru. Lung sounds were recorded at
      eight thoracic sites using a digital stethoscope. 151 (81%) of the recordings
      were eligible for further analysis. Heavy-crying segments were automatically
      rejected and features extracted from spectral and temporal signal representations
      contributed to profiling of lung sounds. RESULTS: Mean age, height, and weight
      among study participants were 2.2 years (SD 1.4), 84.7 cm (SD 13.2), and 12.0 kg
      (SD 3.6), respectively; and, 47% were boys. We identified ten distinct spectral
      and spectro-temporal signal parameters and most demonstrated linear relationships
      with age, height, and weight, while no differences with genders were noted. Older
      children had a faster decaying spectrum than younger ones. Features like spectral
      peak width, lower-frequency Mel-frequency cepstral coefficients, and spectro
      temporal modulations also showed variations with recording site. CONCLUSIONS:
      Lung sound extracted features varied significantly with child characteristics and
      lung site. A comparison with adult studies revealed differences in the extracted
      features for children. While sound-reduction techniques will improve analysis, we
      offer a novel, reproducible tool for sound analysis in real-world environments.

PMID- 24943263
TI  - Differential effect of COX1 and COX2 inhibitors on renal outcomes following
      ischemic acute kidney injury.
AB  - BACKGROUND/AIMS: We have previously shown that 1 mg/kg indomethacin improves
      expression and functionality of renal organic anion transporters Oat1 and Oat3
      after renal ischemia and furthermore improves renal outcome after ischemia. As we
      detected differential effects of COX1 or COX2 inhibitors on organic anion
      transport after ischemia and reperfusion in culture, we investigated the effect
      of the SC560 (COX1 inhibitor) and SC58125 (COX2 inhibitor) on expression of
      Oat1/3 and renal outcome after ischemic acute kidney injury (iAKI). METHODS: iAKI
      was induced in rats by bilateral clamping of renal arteries for 45 min. SC560 or
      SC58125 (1 mg/kg each) were given intraperitoneally as soon as reperfusion
      started. Sham-treated animals served as controls. Oat1/3 were determined by qPCR
      and Western blot. Glomerular filtration rate (GFR), p-aminohippurate (PAH)
      clearance and PAH extraction ratio was determined. All parameters were detected
      24 h after ischemia. Renal plasma flow was calculated. RESULTS: In clamped
      animals SC560 (COX1 inhibitor) restored expression of Oat1/3, as well as renal
      perfusion. Additionally, SC560 substantially improved kidney function as measured
      by GFR. Application of the COX2 inhibitor SC58125 did not exert these beneficial
      effects. CONCLUSION: Our study indicates that COX1 inhibitor SC560 applied after
      ischemia prevents ischemia-induced downregulation of Oat1/3 during reperfusion
      and has a substantial protective effect on kidney function. Whether and to what
      particular extent this apparent improvement of function is mechanistically due to
      beneficial effects on tubular function, renal perfusion or glomerular filtration
      will be the scope of future studies.

PMID- 24943265
TI  - A charge optimized many-body (COMB) potential for titanium and titania.
AB  - This work proposes an empirical, variable charge potential for Ti and TiO(2)
      systems based on the charge-optimized many-body (COMB) potential framework. The
      parameters of the potential function are fit to the structural and mechanical
      properties of the Ti hcp phase, the TiO(2) rutile phase, and the energetics of
      polymorphs of both Ti and TiO(2). The relative stabilities of TiO(2) rutile
      surfaces are predicted and compared to the results of density functional theory
      (DFT) and empirical potential calculations. The transferability of the developed
      potential is demonstrated by determining the adsorption energy of Cu clusters of
      various sizes on the rutile TiO(2)(1 1 0) surface using molecular dynamics
      simulations. The results indicate that the adsorption energy is dependent on the
      number of Cu-Cu bonds and Cu-O bonds formed at the Cu/TiO(2) interface. The
      adsorption energies of Cu clusters on the reduced and oxidized TiO(2)(1 1 0)
      surfaces are also investigated, and the COMB potential predicts enhanced bonding
      between Cu clusters and the oxidized surface, which is consistent with both
      experimental observations and the results of DFT calculations for other
      transition metals (Au and Ag) on this oxidized surface.

PMID- 24943267
TI  - Zwicknia gen. n., a new genus for the Capnia bifrons species group, with
      descriptions of three new species based on morphology, drumming signals and
      molecular genetics, and a synopsis of the West Palaearctic and Nearctic genera of
      Capniidae (Plecoptera).
AB  - Zwicknia Muranyi, gen. n. is erected for the Capnia bifrons species group sensu
      Zhiltzova, 2001 with the description of three new species based on morphology,
      mating call, and the mitochondrial DNA marker cytochrome c oxidase I: Z. acuta
      Muranyi & Orci, sp. n., Z. kovacsi Muranyi & Gamboa, sp. n. and Z. rupprechti
      Muranyi, Orci & Gamboa, sp. n.. Zwicknia bifrons (Newman, 1838) comb. n. is
      selected as the type species and redescribed. The other three species placed into
      Zwicknia, gen. n., Z. sevanica (Zhiltzova, 1964) comb. n., Z. tuberculata
      (Zhiltzova, 1964) comb. n., and Z. turkestanica (Kimmins, 1950) comb. n. are
      redescribed based only on morphological characters. Comparative morphological
      studies and newly discovered characters of the genitalia has allowed for the
      first time a synopsis of the adults of the West Palaearctic and Nearctic genera
      of Capniidae. Arsapnia Banks, 1897 (type species: A. decepta Banks, 1897 comb.
      rev.) is removed from synonymy with Capnia Pictet, 1841 with new combinations,
      Arsapnia arapahoe (Nelson & Kondratieff, 1988) comb. n., A. coyote (Nelson &
      Baumann, 1987) comb. n., A. pileata (Jewett, 1966) comb. n., A. sequoia (Nelson &
      Baumann, 1987) comb. n., A. teresa (Claassen, 1924) comb. n., A. tumida
      (Claassen, 1924) comb. n., and A. utahensis (Gaufin & Jewett, 1962) comb. n. A
      new sensu stricto diagnosis of Capnia is proposed with comments on the taxa
      retained in Capnia sensu lato. 

PMID- 24943266
TI  - Facile fabrication of magnetically recyclable metal-organic framework
      nanocomposites for highly efficient and selective catalytic oxidation of benzylic
      C-H bonds.
AB  - HKUST-1@Fe3O4 chemically bonded core-shell nanoparticles have been prepared by
      growing HKUST-1 thin layers joined by carboxyl groups onto Fe3O4 nanospheres.
      These magnetic core-shell MOF nanostructures show exceptional catalytic activity
      for the oxidation of benzylic C-H bonds and they can be recovered by magnetic
      separation and reused without losing any activity. 

PMID- 24943264
TI  - Both plasmacytoid dendritic cells and monocytes stimulate natural killer cells
      early during human herpes simplex virus type 1 infections.
AB  - Herpes simplex virus type 1 (HSV-1), a member of the herpes virus family, is
      characterized by a short replication cycle, high cytopathogenicity and distinct
      neurotropism. Primary infection and reactivation may cause severe diseases in
      immunocompetent and immunosuppressed individuals. This study investigated the
      role of human plasmacytoid dendritic cells (pDC) in the activation of natural
      killer (NK) cells for the control of herpesviral infections. Within peripheral
      blood mononuclear cells, UV-inactivated HSV-1 and CpG-A induced CD69 up
      regulation on NK cells, whereas infectious HSV-1 was particularly active in
      inducing NK cell effector functions interferon-gamma (IFN-gamma) secretion and
      degranulation. The pDC-derived IFN-alpha significantly contributed to NK cell
      activation, as evident from neutralization and cell depletion experiments. In
      addition, monocyte-derived tumour necrosis factor-alpha (TNF-alpha) induced after
      exposure to infectious HSV-1 was found to stimulate IFN-gamma secretion. A
      minority of monocytes was shown to be non-productively infected in experiments
      using fluorescently labelled viruses and quantitative PCR analyses. HSV-1-exposed
      monocytes up-regulated classical HLA-ABC and non-classical HLA-E molecules at the
      cell surface in an IFN-alpha-dependent manner, whereas stress molecules MICA/B
      were not induced. Notably, depletion of monocytes reduced NK cell effector
      functions induced by infectious HSV-1 (P < 0.05). Altogether, our data suggest a
      model in which HSV-1-stimulated pDC and monocytes activate NK cells via secretion
      of IFN-alpha and TNF-alpha. In addition, infection of monocytes induces NK cell
      effector functions via TNF-alpha-dependent and TNF-alpha-independent mechanisms.
      Hence, pDC and monocytes, which are among the first cells infiltrating herpetic
      lesions, appear to have important bystander functions for NK cells to control
      these viral infections.

PMID- 24943268
TI  - Scale insect genus-group names and their families (Hemiptera: Sternorrhyncha:
      Coccoidea).
AB  - Genus names of the scale insects (Hemiptera: Coccoidea) are listed with their
      current families. The list includes all generic names that are currently valid
      with synonyms, unjustified emendations, homonyms, nomia nuda and misspellings.
      The list has been compiled from many sources as discussed in the introduction.
      This is the first list to be prepared in recent years of all generic names and it
      is in alphabetical order. 

PMID- 24943269
TI  - Activity-dependent Notch signalling in the hypothalamic-neurohypophysial system
      of adult mouse brains.
AB  - Notch signalling has a key role in cell fate specification in developing brains;
      however, recent studies have shown that Notch signalling also participates in the
      regulation of synaptic plasticity in adult brains. In the present study, we
      examined the expression of Notch3 and Delta-like ligand 4 (DLL4) in the
      hypothalamic-neurohypophysial system (HNS) of the adult mouse. The expression of
      DLL4 was higher in the supraoptic nucleus (SON) and paraventricular nucleus (PVN)
      compared to adjacent hypothalamic regions. Double-labelling immunohistochemistry
      using vesicular GABA transporter and glutamate transporter revealed that DLL4 was
      localised at a subpopulation of excitatory and inhibitory axonal boutons against
      somatodendrites of arginine vasopressin (AVP)- and oxytocin (OXT)-containing
      magnocellular neurones. In the neurohypophysis (NH), the expression of DLL4 was
      seen at OXT- but not AVP-containing axonal terminals. The expression of Notch3
      was seen at somatodendrites of AVP- and OXT-containing magnocellular neurones in
      the SON and PVN and at pituicytes in the NH. Chronic physiological stimulation by
      salt loading, which remarkably enhances the release of AVP and OXT, decreased the
      number of DLL4-immunoreactive axonal boutons in the SON and PVN. Moreover,
      chronic and acute osmotic stimulation promoted proteolytic cleavage of Notch3 to
      yield the intracellular fragments of Notch3 in the HNS. Thus, the present study
      demonstrates activity-dependent reduction of DLL4 expression and proteolytic
      cleavage of Notch3 in the HNS, suggesting that Notch signalling possibly
      participates in synaptic interaction in the hypothalamic nuclei and neuroglial
      interaction in the NH. 

PMID- 24943271
TI  - Long-term reorganization of structural brain networks in a rabbit model of
      intrauterine growth restriction.
AB  - Characterization of brain changes produced by intrauterine growth restriction
      (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This
      condition affects 5-10% of all pregnancies and is associated with a wide range of
      neurodevelopmental disorders. Better understanding of the brain reorganization
      produced by IUGR opens a window of opportunity to find potential imaging
      biomarkers in order to identify the infants with a high risk of having
      neurodevelopmental problems and apply therapies to improve their outcomes.
      Structural brain networks obtained from diffusion magnetic resonance imaging
      (MRI) is a promising tool to study brain reorganization and to be used as a
      biomarker of neurodevelopmental alterations. In the present study this technique
      is applied to a rabbit animal model of IUGR, which presents some advantages
      including a controlled environment and the possibility to obtain high quality MRI
      with long acquisition times. Using a Q-Ball diffusion model, and a previously
      published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14
      control rabbits at 70 days of age (equivalent to pre-adolescence human age) were
      obtained. The analysis of graph theory features showed a decreased network
      infrastructure (degree and binary global efficiency) associated with IUGR
      condition and a set of generalized fractional anisotropy (GFA) weighted measures
      associated with abnormal neurobehavior. Interestingly, when assessing the brain
      network organization independently of network infrastructure by means of
      normalized networks, IUGR showed increased global and local efficiencies. We
      hypothesize that this effect could reflect a compensatory response to reduced
      infrastructure in IUGR. These results present new evidence on the long-term
      persistence of the brain reorganization produced by IUGR that could underlie
      behavioral and developmental alterations previously described. The described
      changes in network organization have the potential to be used as biomarkers to
      monitor brain changes produced by experimental therapies in IUGR animal model.

PMID- 24943270
TI  - Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading
      glioma cells.
AB  - Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange
      sites for ions, metabolites and energy substrates from the blood to the brain.
      They maintain endothelial tight junctions that form the blood-brain barrier (BBB)
      and release vasoactive molecules that regulate vascular tone. Malignant gliomas
      are highly invasive tumours that use the perivascular space for invasion and co
      opt existing vessels as satellite tumour form. Here we use a clinically relevant
      mouse model of glioma and find that glioma cells, as they populate the
      perivascular space of preexisting vessels, displace astrocytic endfeet from
      endothelial or vascular smooth muscle cells. This causes a focal breach in the
      BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma
      cells seize control over the regulation of vascular tone through Ca(2+)-dependent
      release of K(+). These findings have important clinical implications regarding
      blood flow in the tumour-associated brain and the ability to locally deliver
      chemotherapeutic drugs in disease. 

PMID- 24943273
TI  - Temporal lobe sulcal pattern and the bony impressions in the middle cranial
      fossa: the case of the el Sidron (Spain) neandertal sample.
AB  - Correspondence between temporal lobe sulcal pattern and bony impressions on the
      middle cranial fossae (MCF) was analyzed. MCF bone remains (SD-359, SD-315, and
      SD-1219) from the El Sidron (Spain) neandertal site are analyzed in this context.
      Direct comparison of the soft and hard tissues from the same individual was
      studied by means of: 1) dissection of two human heads; 2) optic (white light)
      surface scans; 3) computed tomography and magnetic resonance of the same head.
      The inferior temporal sulcus and gyrus are the features most strongly influencing
      MCF bone surface. The Superior temporal sulcus and middle temporal and fusiform
      gyri also leave imprints. Temporal lobe form differs between Homo sapiens and
      neandertals. A wider and larger post-arcuate fossa (posterior limit of Brodmann
      area 20 and the anterior portion of area 37) is present in modern humans as
      compared to neandertals. However other traits of the MCF surface are similar in
      these two large-brained human groups. A conspicuous variation is appreciated in
      the more vertical location of the inferior temporal gyrus in H. sapiens. In
      parallel, structures of the lower surface of the temporal lobe are more
      sagittally orientated. Grooves accommodating the fusiform and the lower temporal
      sulci become grossly parallel to the temporal squama. These differences can be
      understood within the context of a supero-lateral deployment of the lobe in H.
      sapiens, a pattern previously identified (Bastir et al., Nat Commun 2 (2011) 588
      595). Regarding dural sinus pattern, a higher incidence of petrosquamous sinus is
      detected in neandertal samples.

PMID- 24943272
TI  - Prediction of chemotherapeutic response in bladder cancer using K-means
      clustering of dynamic contrast-enhanced (DCE)-MRI pharmacokinetic parameters.
AB  - PURPOSE: To apply k-means clustering of two pharmacokinetic parameters derived
      from 3T dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict
      the chemotherapeutic response in bladder cancer at the mid-cycle timepoint.
      MATERIALS AND METHODS: With the predetermined number of three clusters, k-means
      clustering was performed on nondimensionalized Amp and kep estimates of each
      bladder tumor. Three cluster volume fractions (VFs) were calculated for each
      tumor at baseline and mid-cycle. The changes of three cluster VFs from baseline
      to mid-cycle were correlated with the tumor's chemotherapeutic response. Receiver
      operating-characteristics curve analysis was used to evaluate the performance of
      each cluster VF change as a biomarker of chemotherapeutic response in bladder
      cancer. RESULTS: The k-means clustering partitioned each bladder tumor into
      cluster 1 (low kep and low Amp), cluster 2 (low kep and high Amp), cluster 3
      (high kep and low Amp). The changes of all three cluster VFs were found to be
      associated with bladder tumor response to chemotherapy. The VF change of cluster
      2 presented with the highest area-under-the-curve value (0.96) and the highest
      sensitivity/specificity/accuracy (96%/100%/97%) with a selected cutoff value.
      CONCLUSION: The k-means clustering of the two DCE-MRI pharmacokinetic parameters
      can characterize the complex microcirculatory changes within a bladder tumor to
      enable early prediction of the tumor's chemotherapeutic response.

PMID- 24943274
TI  - Engineered T cells for cancer therapy.
AB  - It is now well established that the immune system can control and eliminate
      cancer cells. Adoptive T cell transfer has the potential to overcome the
      significant limitations associated with vaccine-based strategies in patients who
      are often immune compromised. Application of the emerging discipline of synthetic
      biology to cancer, which combines elements of genetic engineering and molecular
      biology to create new biological structures with enhanced functionalities, is the
      subject of this focused research review. 

PMID- 24943276
TI  - A traditional Japanese medicine--Hangeshashinto (TJ-14)--alleviates
      chemoradiation-induced mucositis and improves rates of treatment completion.
AB  - PURPOSE: Oral mucositis induced by radiation or chemoradiation can cause
      devastating quality of life issues for patients undergoing treatment for head and
      neck cancer. In this study, we investigated the efficacy of a traditional
      Japanese medicine-Hangeshashinto (TJ-14)-for (chemo)radiation-induced oral
      mucositis. METHODS: Eighty patients who underwent whole neck radiation of >60 Gy
      with or without chemotherapy (high-dose cisplatin or low-dose docetaxel) were
      enrolled in this retrospective study; 40 had received TJ-14 during treatment, and
      40 had not (controls). Factors related to alleviation of oral mucositis were
      identified by multivariate logistic regression analysis. Rates of completion of
      (chemo)radiation treatments were compared between the patients who received TJ-14
      and the control group according to the treatment regimen. The comparison of the
      nutrition status between groups was also performed. RESULTS: Multivariate
      analysis indicated that the use of TJ-14 (p = 0.019), gender (p = 0.024), and
      primary tumor location (p = 0.028) were significant factors associated with the
      severity of oral mucositis. TJ-14 was associated with a significantly improved
      rate of completion of chemoradiation with cisplatin (p = 0.002). In the
      investigation of nutritional status, only serum albumin was significantly
      maintained better in the TJ-14 group than the control group in terms of mean
      change before and after (chemo)radiation (p = 0.024). CONCLUSIONS: The present
      study indicates that TJ-14 is effective for ameliorating oral mucositis induced
      by (chemo)radiation in patients with head and neck cancers. TJ-14 was associated
      with improved completion rates of chemoradiation treatments with cisplatin. A
      randomized controlled trial is necessary to confirm the efficacy of TJ-14 for
      chemoradiation-induced mucositis in head and neck cancer patients.

PMID- 24943275
TI  - Radiation-induced autophagy potentiates immunotherapy of cancer via up-regulation
      of mannose 6-phosphate receptor on tumor cells in mice.
AB  - There is a significant body of evidence demonstrating that radiation therapy
      (XRT) enhances the effect of immune therapy. However, the precise mechanisms by
      which XRT potentiates the immunotherapy of cancer remain elusive. Here, we report
      that XRT potentiates the effect of immune therapy via induction of autophagy and
      resultant trafficking of mannose-6-phopsphate receptor (MPR) to the cell surface.
      Irradiation of different tumor cells caused substantial up-regulation of MPR on
      the cell surface in vitro and in vivo. Down-regulation of MPR in tumor cells with
      shRNA completely abrogated the combined effect of XRT and immunotherapy (CTLA4
      antibody) in B16F10-bearing mice without changes in the tumor-specific responses
      of T cells. Radiation-induced MPR up-regulation was the result of redistribution
      of the receptor to the cell surface. This effect was caused by autophagy with
      redirection of MPR to autophagosomes in a clathrin-dependent manner. In
      autophagosomes, MPR lost its natural ligands, which resulted in subsequent
      trafficking of empty receptor(s) back to the surface. Together, our data
      demonstrated a novel mechanism by which XRT can enhance the effect of
      immunotherapy and the molecular mechanism of this process.

PMID- 24943283
TI  - National Adolescent Treatment Trial for Obesity in Kuwait (NATTO): project design
      and results of a randomised controlled trial of a good practice approach to
      treatment of adolescent obesity in Kuwait.
AB  - BACKGROUND: Few randomised controlled trials (RCTs) of interventions for the
      treatment of adolescent obesity have taken place outside the western world. This
      RCT tested whether a simple 'good practice' intervention for the treatment of
      adolescent obesity would have a greater impact on weight status and other
      outcomes than a referral to primary care (control) in adolescents in Kuwait City.
      METHODS: We report on an assessor-blinded RCT of a treatment intervention in 82
      obese 10- to 14-year-olds (mean age 12.4, SD 1.2 years), randomised to a good
      practice treatment or primary care control group over 6 months. The good practice
      intervention was intended as relatively low intensity (6 hours contact over 24
      weeks, group-based), aiming to change sedentary behaviour, physical activity, and
      diet. The primary outcome was a change in body mass index (BMI) Z score; other
      outcomes were changes in waist circumference and blood pressure. RESULTS: The
      retention of subjects to follow up was acceptable (n = 31 from the intervention
      group, and n = 32 from the control group), but engagement with both the
      intervention and control treatment was poor. Treatment had no significant effect
      on BMI Z score relative to control, and no other significant benefits to
      intervention were observed. CONCLUSIONS: The trial was feasible, but highlights
      the need to engage obese adolescents and their families in the interventions
      being trialled. The trial should inform the development of future adolescent
      obesity treatment trials in the Gulf States with the incorporation of qualitative
      assessment in future intervention trials. TRIAL REGISTRATION: RCT Registered as
      National Adolescent Treatment Trial for Obesity in Kuwait (NATTO):
      http://www.controlled-trials.com/ISRCTN37457227, 1 December 2009.

PMID- 24943284
TI  - Trigeminal neuralgia related to megadolichobasilar artery compression: a
      prospective series of twenty-nine patients treated with gamma knife surgery, with
      more than one year of follow-up.
AB  - BACKGROUND: Trigeminal neuralgia (TN) secondary to megadolichobasilar artery
      (MBA) compression is considerably difficult to manage surgically. OBJECTIVE: This
      study aims to evaluate the safety/efficacy of Gamma Knife surgery (GKS) in this
      special group of patients. METHODS: Between July 1992 and November 2010, 29
      patients with >1 year of follow-up presenting with MBA compression were treated
      with GKS at Timone University Hospital. Radiosurgery was performed using a Gamma
      Knife (model B, C or Perfexion). A single 4-mm isocenter was positioned in the
      cisternal portion of the trigeminal nerve at a median distance of 9.1 mm (range:
      6-18.2 mm) from the emergence. RESULTS: The median follow-up period was 46.1
      months (range: 12.9-157.9 months). Initially, all patients (100%) were pain free;
      the average time to complete pain relief was 13.5 days (range: 0-240 days). Their
      actuarial probability of remaining pain free without medication at 0.5, 1 and 2
      years was 93.1, 79.3 and 75.7%, respectively, and remained stable until 13 years
      after treatment. The actuarial probability of hypoesthesia onset at 6 months was
      4.3%; at 1 year it reached 13% and remained stable until 13 years after
      treatment. CONCLUSIONS: GKS proved to be reasonably safe and effective on a long
      term basis as a first- and/or second-line surgical treatment for TN due to MBA
      compression.

PMID- 24943277
TI  - The cost effectiveness of a tailored, web-based care program to enhance
      postoperative recovery in gynecologic patients in comparison with usual care:
      protocol of a stepped wedge cluster randomized controlled trial.
AB  - BACKGROUND: The length of recovery after benign gynecological surgery and return
      to work frequently exceeds the period that is recommended or expected by
      specialists. A prolonged recovery is associated with a poorer quality of life. In
      addition, costs due to prolonged sick leave following gynecological surgery cause
      a significant financial burden on society. OBJECTIVE: The objective of our study
      was to present the protocol of a stepped wedge cluster randomized controlled
      trial to evaluate the cost effectiveness of a new care program for patients
      undergoing hysterectomy and/or adnexal surgery for benign disease, compared to
      the usual care. METHODS: The care program under study, designed to improve
      convalescence and to prevent delayed return to work, targets two levels. At the
      hospital level, guidelines will be distributed among clinical staff in order to
      stimulate evidence-based patient education. At the patient level, additional
      perioperative guidance is provided by means of an eHealth intervention, equipping
      patients with tailored convalescence advice, and an occupational intervention is
      available for those patients at risk of prolonged sick leave. Due to the stepped
      wedge design of the trial, the care program will be sequentially rolled out among
      the 9 participating hospitals, from which the patients are recruited. Eligible
      for this study are employed women, 18-65 years of age, who are scheduled for
      hysterectomy and/or laparoscopic adnexal surgery. The primary outcome is full
      sustainable return to work. The secondary outcomes include general recovery,
      quality of life, self-efficacy, coping, and pain. The data will be collected by
      means of self-reported electronic questionnaires before surgery and at 2, 6, 12,
      26, and 52 weeks after surgery. Sick leave and cost data are measured by monthly
      sick leave calendars, and cost diaries during the 12 month follow-up period. The
      economic evaluation will be performed from the societal perspective. All
      statistical analyses will be conducted according to the intention-to-treat
      principle. RESULTS: The enrollment of the patients started October 2011. The
      follow-up period will be completed in August 2014. Data cleaning or analysis has
      not begun as of this article's submission. CONCLUSIONS: We hypothesize the care
      program to be effective by means of improving convalescence and reducing costs
      associated with productivity losses following gynecological surgery. The results
      of this study will enable health care policy makers to decide about future
      implementation of this care program on a broad scale. TRIAL REGISTRATION:
      Netherlands Trial Register: NTR2933;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2933 (Archived by
      WebCite at http://www.webcitation.org/6Q7exPG84).

PMID- 24943285
TI  - Effects of a DASH-like diet containing lean beef on vascular health.
AB  - A DASH (dietary approaches to stop hypertension) dietary pattern rich in fruits
      and vegetables and low-fat dairy products with increased dietary protein provided
      primarily from plant protein sources decreases blood pressure. No studies,
      however, have evaluated the effects of a DASH-like diet with increased dietary
      protein from lean beef on blood pressure and vascular health. The aim of this
      study was to study the effect of DASH-like diets that provided different amounts
      of protein from lean beef (DASH 28 g beef per day; beef in an optimal lean diet
      (BOLD) 113 g beef per day; beef in an optimal lean diet plus additional protein
      (BOLD+) 153 g beef per day) on blood pressure, endothelial function and vascular
      reactivity versus a healthy American diet (HAD). Using a randomized, crossover
      study design, 36 normotensive participants (systolic blood pressure (SBP), 116 +/
      3.6 mm Hg) were fed four isocaloric diets,: HAD (33% total fat, 12% saturated
      fatty acids (SFA), 17% protein (PRO), 20 g beef per day), DASH (27% total fat, 6%
      SFA, 18% PRO, 28 g beef per day), BOLD (28% total fat, 6% SFA, 19% PRO, 113 g
      beef per day) and BOLD+ (28% total fat, 6% SFA, 27% PRO, 153 g beef per day), for
      5 weeks. SBP decreased (P<0.05) in subjects on the BOLD+ diet (111.4 +/- 1.9 mm
      Hg) versus HAD (115.7 +/- 1.9). There were no significant effects of the DASH and
      BOLD diets on SBP. Augmentation index (AI) was significantly reduced in
      participants on the BOLD diet (-4.1%). There were no significant effects of the
      dietary treatments on diastolic blood pressure or endothelial function (as
      measured by peripheral arterial tonometry). A moderate protein DASH-like diet
      including lean beef decreased SBP in normotensive individuals. The inclusion of
      lean beef in a heart healthy diet also reduced peripheral vascular constriction.

PMID- 24943286
TI  - Radial arterial compliance measurement by fiber Bragg grating pulse recorder.
AB  - In the present work, we report a novel, in vivo, noninvasive technique to
      determine radial arterial compliance using the radial arterial pressure pulse
      waveform (RAPPW) acquired by fiber Bragg grating pulse recorder (FBGPR). The
      radial arterial compliance of the subject can be measured during
      sphygmomanometric examination by the unique signatures of arterial diametrical
      variations and the beat-to-beat pulse pressure acquired simultaneously from the
      RAPPW recorded using FBGPR. This proposed technique has been validated against
      the radial arterial diametrical measurements obtained from the color Doppler
      ultrasound. Two distinct trials have been illustrated in this work and the
      results from both techniques have been found to be in good agreement with each
      other. 

PMID- 24943287
TI  - The effects of endothelial nitric oxide synthase tagSNPs on nitrite levels and
      risk of hypertension and obesity in children and adolescents.
AB  - Obesity and the nitric oxide synthase 3 (NOS3) gene polymorphisms are associated
      with nitrite levels and hypertension. However, no study has tested the hypothesis
      that NOS3 tagSNPs rs3918226, rs3918188, rs743506 and rs7830 affect nitrite levels
      and are associated with hypertension in childhood obesity. We investigated the
      association of these NOS3 tagSNPs and the haplotypes formed by them with
      hypertension and with nitrite levels in children and adolescents with obesity and
      with obesity plus hypertension. We studied 355 subjects: 174 healthy (controls),
      109 normotensive obese, and 72 obese children and adolescents with obesity plus
      hypertension. Genotypes were determined by Taqman allele discrimination assay and
      real-time PCR. We compared the distribution of NOS3 tagSNP genotypes, alleles and
      haplotypes in the three groups of subjects. Nitrite levels were determined by
      ozone-based chemiluminescence. Nitrite levels were affected by the rs3918226
      polymorphism (P<0.05) but not by NOS3 haplotypes. There was no association
      between the tagSNPs studied and hypertension in children and adolescents. Our
      findings show that the NOS3 tagSNP rs3918226 is associated with NO production in
      children and adolescents, and suggest that this polymorphism may have an impact
      on cardiovascular health. Further studies are needed to better clarify the
      effects of this polymorphism on cardiovascular risk. 

PMID- 24943288
TI  - Cardiovascular complications from consumption of high energy drinks: recent
      evidence.
AB  - The energy drinks (ED) are caffeinated beverages that are popular among teenagers
      and young adults. They are aggressively marketed as providing alertness, energy
      and sex prowess. The EDs in addition to caffeine contain several plant stimulants
      and simple sugars, which increase their caloric content. The caffeine
      concentration in these drinks is high and their overconsumption could lead to
      insomnia, agitation, tremors and cardiovascular complications including sudden
      death. Alcohol is often mixed with EDs (AMEDs) in the wrong perception that the
      caffeine in the EDs will prevent the drowsiness and sleepiness from alcohol and
      allow the person to consume more alcohol. This false perception, could lead to
      alcohol intoxication and the taking of risky decisions, like driving under the
      influence of alcohol and the risk of serious physical harm to themselves and
      others. To prevent the problem of consumption of EDs and AMEDs, the caring
      physician could help by advising the parents and his young patients about the
      serious health risks from the consumption of these drinks. In order to grasp the
      extend of the problem of ED and AMED consumption, we did a Medline search of the
      English language literature from January 2010 to December 2013, using the terms
      EDs and alcohol-mixed EDs. All the findings from the recent studies regarding the
      cardiovascular complications from the consumption of EDs and AMEDs together with
      collateral literature will be discussed in this review. 

PMID- 24943289
TI  - The effect of chlorogenic acid on blood pressure: a systematic review and meta
      analysis of randomized clinical trials.
AB  - Several dietary supplements are currently marketed for management of
      hypertension, but the evidence for effectiveness is conflicting. Our objective
      was to critically appraise and evaluate the evidence for the effectiveness of
      chlorogenic acids (CGAs) on blood pressure, using data from published randomized
      clinical trials (RCTs). Electronic searches were conducted in Medline, Embase,
      Amed, Cinahl and The Cochrane Library. We also hand-searched the bibliographies
      of all retrieved articles. Two reviewers independently determined the eligibility
      of studies and extracted the data. The reporting quality of all included studies
      was assessed by the use of a quality assessment checklist adapted from the
      Consolidated Standard of Reporting Trials Statement. Disagreements were resolved
      through discussion. Seven eligible studies were identified, and five including
      364 participants were included. There were variations in the reporting quality of
      the included RCTs. Meta-analysis revealed a statistically significant reduction
      in systolic blood pressure in favour of CGA (mean difference (MD): -4.31 mm Hg;
      95% confidence interval (CI): -5.60 to -3.01; I(2)=65%; P<0.00001). Meta-analysis
      also showed a significant reduction in diastolic blood pressure favouring CGA
      (MD: -3.68 mm Hg; 95% CI: -3.91 to -3.45; I(2)=97%; P<0.00001). All studies
      reported no adverse events. In conclusion, the evidence from published RCTs
      suggests that CGA intake causes statistically significant reductions in systolic
      and diastolic blood pressures. The size of the effect is moderate. Few clinical
      trials have been conducted; they vary in design and methodology and are confined
      to Asian populations and funded by CGA manufacturers. Large independent trials
      evaluating the effects of CGA on blood pressure are warranted. 

PMID- 24943290
TI  - Pregnancy normalized familial hyperaldosteronism type I: a novel role for
      progesterone?

PMID- 24943291
TI  - Reversible photochemical and thermal isomerization of azaboratabisnorcaradiene to
      azaborabenzotropilidene.
AB  - Two new tricyclic 1,2-azaboratabisnorcaradiene molecules (1 b and 2 b) generated
      through the photoisomerization of N-methyl-2-phenylimidazolyl-chelated
      dimesitylboranes (1 a and 2 a) have been found to undergo unusual
      photoisomerization, producing the first examples of 1,2-azaborabenzotropilidenes
      (1 c and 2 c), accompanied by a distinct color change, upon irradiation at 350
      nm. Compounds 1 c and 2 c contain a conjugated alkylideneborane unit and can be
      fully reverted back to 1 b and 2 b, and subsequently to 1 a and 2 a upon heating.
      The mechanistic pathway of the new isomerism has been established to involve
      "walk" rearrangements by DFT computational studies. 

PMID- 24943292
TI  - P2Y12 platelet function assay as a key predictor for bleeding risk in coronary
      artery bypass grafting.

PMID- 24943293
TI  - Negative surveillance endoscopy occurs frequently in patients with short-segment
      non-dysplastic Barrett's esophagus.
AB  - Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to
      detect intestinal metaplasia (IM), or negative surveillance, is known to occur in
      clinical practice, although the frequency and possible outcomes in a large cohort
      in clinical practice is not well described. The goals of this study were to
      define frequency in which negative surveillance occurs and endoscopic outcomes in
      a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of
      patients newly diagnosed with short segment NDBE at an outpatient academic
      tertiary care center between 2003 and 2011 were reviewed. Only those with one or
      more surveillance endoscopies were included to define a frequency of negative
      surveillance. Included patients were further assessed if they had two or more
      surveillance endoscopies and were classified into groups as sampling error or
      negative IM on consecutive surveillances based on the results of their
      surveillance endoscopies. The frequency of a negative surveillance endoscopy in
      all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for
      IM of 468 total surveillance exams). A negative surveillance endoscopy occurred
      in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on
      consecutive surveillance endoscopies in 55.88% of those with >= 2 surveillance
      endoscopies and an initially negative surveillance exam. The frequency of
      negative IM on consecutive surveillances was 19.00% of all patients who had two
      surveillance endoscopies. When the index diagnostic Barrett's esophagus segment
      length was < 1 cm, 32.14% (18/56) of all patients (with >= 2 surveillance
      endoscopies) had negative IM on consecutive surveillance endoscopies. Negative
      surveillance occurs frequently in short-segment NDBE. When an initial negative
      surveillance endoscopy occurs, it may be due to either a sampling error or lack
      of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed,
      a significant proportion of patients may go on to have continuously undetected IM
      on consecutive surveillance endoscopic exams without intervention.

PMID- 24943294
TI  - Testosterone and cardiovascular risk in men.
AB  - Testosterone deficiency is highly prevalent in men with cardiovascular disease
      (CVD) and is associated with an increased mortality. Low testosterone also has an
      adverse effect on several cardiovascular risk factors, which include insulin
      resistance, diabetes, dyslipidaemia, central adiposity and endothelial
      dysfunction. Male gender is a well-recognised risk factor for premature CVD and
      mortality. The question of whether or not testosterone deficiency is a
      contributory factor to atherogenesis or merely a biomarker of ill health arises.
      Animal studies and experiments on isolated cells indicate that many of the
      mechanisms intimate to the atherosclerotic process are beneficially modulated by
      testosterone. Epidemiological studies have shown that men with endogenous
      testosterone levels in the mid-upper normal range have reduced cardiovascular
      events and mortality compared to those with low or lower range, and with high
      range testosterone. Testosterone replacement in men diagnosed with hypogonadism
      where mid-normal range levels are achieved have shown a beneficial effect on
      several cardiovascular risk factors, cardiac ischaemia, functional exercise
      capacity and improved mortality. Yet studies where patients were either
      undertreated or given high-dose testosterone have been associated with an
      increased risk of cardiovascular-related events. Clinical monitoring and
      titration of testosterone dose is therefore of paramount importance.

PMID- 24943295
TI  - Hormone therapy and venous thromboembolism among postmenopausal women.
AB  - Venous thromboembolism (VTE) is a major harmful effect of hormone therapy (HT)
      among postmenopausal women. A large variety of HT can be used with significant
      differences in adverse effects. There is evidence that the VTE risk among HT
      users depends on the route of estrogen administration. Oral but not transdermal
      estrogens dose-dependently increase the VTE risk. This difference is supported by
      biological data. Whereas oral estrogens increase thrombin generation and induce
      resistance to activated protein C, transdermal estrogens have minimal effect on
      hemostasis. Past users of oral estrogens have a similar VTE risk to never users.
      Among users of oral estrogens, the VTE risk is higher within the 1st year of
      treatment. The combination of oral estrogen use and either obesity or
      thrombogenic mutations further enhances the VTE risk, whereas transdermal
      estrogens may not confer additional risk in women at high VTE risk. Significant
      differences in the VTE risk between HT preparations are also related to the type
      of concomitant progestogen. The VTE risk is greater in women using
      medroxyprogesterone acetate than in those receiving other progestins, whereas
      micronized progesterone appears safe. Based on the current data, transdermal
      estrogen alone or combined with progesterone could be the safer HT especially in
      women at high risk for thrombosis.

PMID- 24943296
TI  - Cardiovascular and metabolic impact of glucocorticoid replacement therapy.
AB  - Cortisol in man is essential for life. Excess cortisol as in Cushing's syndrome
      and during pharmacological glucocorticoid (GC) therapy is associated with
      increased cardiovascular morbidity and mortality. Recent data from patients with
      adrenal insufficiency (AI) have demonstrated that currently used replacement
      regimens are associated with a poor cardiovascular outcome. In particular, a more
      than doubled vascular mortality rate has been observed in patients with primary
      AI. The unphysiological GC replacement, both in terms of the total daily dose and
      the pattern of delivery, may explain this poor outcome together with an
      inadequate treatment during an intercurrent illness. The mechanism may be both an
      induction of classical metabolic risk factors for vascular disease, such as
      obesity and hypertension, but also an unphysiological cortisol exposure to the
      vascular endothelium and the immune system that may induce an accelerated
      atherosclerotic process. This review summarizes some of the cardiovascular data
      associated with GC excess and outcome data in patients with AI. Studies that have
      compared various regimens for replacement therapy will be addressed and recent
      developments that may improve outcome in patients with AI will be discussed.

PMID- 24943297
TI  - Cardiovascular disease and thyroid function.
AB  - Thyroid function has a profound effect on the heart, and both all-cause and
      cardiovascular mortality rates are increased in hyperthyroidism. New-onset atrial
      fibrillation carries a prolonged risk for the development of hyperthyroidism,
      suggesting altered availability of thyroid hormones at the cellular level.
      Subclinical hyperthyroidism is associated with increased left ventricular mass of
      the heart, which reverts after obtaining euthyroidism. Mortality and risk of
      major cardiovascular events are increased. Subclinical hypothyroidism is also
      associated with subtle changes in the heart, e.g. its increased stiffness, which
      reverts after treatment with levothyroxine. Mortality seems mildly reduced,
      although the risk of myocardial infarction is increased. The risk of atrial
      fibrillation is related to thyroid function over the whole spectrum: from a
      reduced risk in overt and subclinical hypothyroidism, a progressively increased
      risk in people with different levels of reduced TSH to a physiologically 'dose
      dependent' effect of thyroid hormones on the heart in overt hyperthyroidism.
      Heart failure represents an intriguing clinical situation in which
      triiodothyronine treatment might be beneficial. In conclusion, subclinical
      dysthyroid states affect the heart with subsequent changes in morbidity and
      mortality. Subclinical hyperthyroidism seems a more serious condition than
      subclinical hypothyroidism, which should affect treatment decision in a more
      aggressive manner.

PMID- 24943299
TI  - Genetics of primary aldosteronism.
AB  - Primary aldosteronism (PA) accounts for ~10% of hypertension, which is commonly
      caused by an aldosterone-producing adenoma (APA) or bilateral adrenal
      hyperplasia. Germline mutations producing PA are considered rare and termed
      familial hyperaldosteronism (FH) [1, 2, 3]. Since early 2011, a series of somatic
      mutations confined to the adrenal cortex has been reported, accounting for about
      half of APA. These mutations are in genes encoding components of the Kir 3.4
      (GIRK4) potassium channel (KCNJ5), sodium/potassium and calcium ATPases (ATP1A1
      and ATP2B3) and a voltage-dependent C-type calcium channel (CACNA1D). FH-1
      (glucocorticoid-remediable hyperaldosteronism) results from a chimeric gene (5'
      end of CYP11B1 fused to 3'-end of CYP11B2) and accounts for ~1% of PA. FH-3 is
      very rare, is caused by bilateral expression of mutant KCNJ5 and usually results
      in florid hyperaldosteronism requiring early bilateral adrenalectomy. FH-2 is the
      most common form of hereditary PA (2 first-degree relatives with either an APA or
      bilateral adrenal hyperplasia) and currently thought to represent ~6% of PA; the
      true prevalence may be considerably higher. The mutation(s) causing FH-2 are
      unknown but appear dominant, as is the case for FH-1 and FH-3. No studies have
      been done on possible recessive forms of PA.

PMID- 24943298
TI  - Hormonal alterations in heart failure: anabolic impairment in chronic heart
      failure - diagnostic, prognostic and therapeutic issues.
AB  - Chronic heart failure represents a leading cause of mortality and health care
      expenditure in developed countries. In the last 20 years, medical therapy of
      heart failure has dramatically changed thanks to the introduction of agents able
      to significantly reduce the neurohormonal hyperactivation that underpins the
      syndrome, and to the growing opportunities of electrical therapies. Although
      major advances in terms of improved survival and quality of life have been
      achieved, the reduction in the burden of heart failure is still the primary goal
      of cardiovascular societies. In the last decades, other research lines have also
      grown to complement the neurohormonal paradigm. It is increasingly evident that
      several hormonal systems are down-regulated or impaired in patients with heart
      failure, including growth and thyroid hormones, androgens and insulin. These
      abnormalities could be considered interrelated and linked, in turn, to the
      neurohormonal and cytokine hyperactivation. Since most of these alterations
      provide prognostic information, these new lines of evidence support the extension
      of the classical neurohormonal scheme to a more comprehensive pathophysiological
      model that includes multiple hormonal and metabolic deficiencies. This chapter
      examines the evidence in support of this concept. Preliminary experience
      concerning targeted hormonal supplementation or metabolic modulation is also
      briefly reviewed in this article.

PMID- 24943300
TI  - Adipose tissue dysfunction and inflammation in cardiovascular disease.
AB  - Adipose tissue (AT) was long perceived as a passive lipid storage depot but it is
      now considered as an endocrine organ that produces a large number of mediators
      that affect metabolism, inflammation and coagulation. In obesity, the increased
      size of adipocytes and chronic low-grade inflammation within AT alter its normal
      physiological function. AT dysfunction results in altered production and
      secretion of adipokines, which in turn affect several tissues, e.g. the liver,
      skeletal muscles and vasculature, in a para- or endocrine manner. Numerous
      circulating proinflammatory mediators involved in the development of
      cardiovascular disease (CVD) are directly released from adipocytes, thereby
      linking obesity to an increased cardiovascular risk. In the current chapter, we
      focus, on the one hand, on a small selection of novel adipokines with a
      potentially strong link to CVD: soluble dipeptidyl peptidase-4, visfatin and
      lipocalin-2. On the other hand, we summarize the most recent findings on the
      novel cardioprotective adipokines omentin and apelin.

PMID- 24943301
TI  - Potential peptides in atherosclerosis therapy.
AB  - Atherosclerosis is the main underlying cause of ischemic heart disease and
      related acute cardiovascular complications, including myocardial infarction and
      stroke. In view of the failure of statins to demonstrate a beneficial effect in
      all patients, exhaustive research efforts have unfold into different research
      avenues, in close relation to the increase in basic knowledge regarding
      lipoprotein metabolism, macrophage function and inflammatory conditions
      associated with atherosclerosis. This review focuses specifically on potential
      therapeutic peptides targeting dyslipidemia, macrophage scavenger receptors,
      cholesterol metabolism and anti-inflammatory cytokines as novel therapeutic
      avenues in atherosclerosis.

PMID- 24943303
TI  - Ghrelin and the cardiovascular system.
AB  - Ghrelin is a peptide that was originally isolated from the stomach. It exerts
      potent growth hormone (GH)-releasing and orexigenic activities. Several studies
      have highlighted the therapeutic benefits of ghrelin for the treatment of
      cardiovascular disease. In animal models of chronic heart failure, the
      administration of ghrelin improved cardiac function and remodeling; these
      findings were replicated in human patients with heart failure. Moreover, in an
      animal study, ghrelin administration effectively reduced pulmonary hypertension
      induced by chronic hypoxia. In addition, repeated administration of ghrelin to
      cachectic patients with chronic obstructive pulmonary disease had positive
      effects on overall body function, including muscle wasting, functional capacity
      and sympathetic activity. The administration of ghrelin early after myocardial
      infarction (MI) reduced fatal arrhythmia and related mortality. In ghrelin
      deficient mice, both exogenous and endogenous ghrelin were protective against
      fatal arrhythmia and promoted remodeling after MI. Although the mechanisms
      underlying the effects of ghrelin on the cardiovascular system remain unclear,
      there are indications that its beneficial effects are mediated through both
      direct physiological actions, including increased GH levels, improved energy
      balance and direct actions on cardiovascular cells, and regulation of autonomic
      nervous system activity. Therefore, ghrelin is a promising novel therapeutic
      agent for cardiovascular disease.

PMID- 24943305
TI  - Beyond glycemic control: cardiovascular effects of incretin-based therapies.
AB  - As cardiovascular (CV) disease remains the major cause of mortality and morbidity
      in type 2 diabetes mellitus, reducing macrovascular complications has been a
      major target of antiglycemic therapies. Emerging evidence suggests that incretin
      based therapies are safe and may provide CV and cerebrovascular (CBV) benefits
      beyond those attributable to glycemic control, making the class an attractive
      therapeutic option. However, the mechanisms whereby the various classes of
      incretin-based therapies exert CV and CBV benefits may be distinct and may not
      necessarily lead to similar outcomes. In this chapter, we will discuss the
      potential mechanisms and current understanding of CV and CBV benefits of native
      glucagon-like peptide (GLP)-1, GLP-1 receptor agonists and analogues, and of
      dipeptidyl peptidase-4 inhibitor therapies as a means to better understand
      differences in safety and efficacy.

PMID- 24943304
TI  - Natriuretic peptide system and the heart.
AB  - The natriuretic peptide (NP) family includes atrial (ANP), brain or B-type (BNP)
      and C-type NP (CNP). A huge number of experimental and clinical studies,
      published in the 1st decade of this century, have added further support to the
      hypothesis that endocrine function in the human heart is a relevant component of
      a complex network including endocrine, nervous and immune systems. The NP
      hormones constitute a well-integrated regulatory system and share a similar
      spectrum of biological actions, although there are some differences in biological
      potency between ANP, BNP and CNP. However, several important issues on this field
      need to be investigated further. The production, secretion and peripheral
      degradation pathways of both BNP and CNP should be clarified in detail. In
      particular, the hypothesis that the circulating plasma pool of the prohormone can
      function as a precursor of the active peptide hormone should be demonstrated
      definitively. Recent findings indicate that peripheral processing of circulating
      prohormones could likely be submitted to regulatory rules, which might be
      impaired in patients with heart failure, opening up new perspectives even in the
      treatment of heart failure. This hypothesis suggests a novel pharmacological
      target for drugs inducing and/or modulating the maturation of the prohormone into
      active hormone.

PMID- 24943302
TI  - Interaction between insulin-like growth factor-1 and atherosclerosis and vascular
      aging.
AB  - The process of vascular aging encompasses alterations in the function of
      endothelial (ECs) and vascular smooth muscle cells (VSMCs) via oxidation,
      inflammation, cell senescence and epigenetic modifications, increasing the
      probability of atherosclerosis. Aged vessels exhibit decreased endothelial
      antithrombogenic properties, increased reactive oxygen species generation,
      inflammatory signaling and migration of VSMCs to the subintimal space, impaired
      angiogenesis and increased elastin degradation. The key initiating step in
      atherogenesis is subendothelial accumulation of apolipoprotein B-containing low
      density lipoproteins resulting in activation of ECs and recruitment of monocytes.
      Activated ECs secrete 'chemokines' that interact with cognate chemokine receptors
      on monocytes and promote directional migration. Recruitment of immune cells
      establishes a proinflammatory status, further causing elevated oxidative stress,
      which in turn triggers a series of events including apoptotic or necrotic death
      of vascular and nonvascular cells. Increased oxidative stress is also considered
      to be a key factor in mechanisms of aging-associated changes in tissue integrity
      and function. Experimental evidence indicates that insulin-like growth factor-1
      exerts antioxidant, anti-inflammatory and pro-survival effects on the
      vasculature, reducing atherosclerotic plaque burden and promoting features of
      atherosclerotic plaque stability.

PMID- 24943307
TI  - Real-time ultrasound-guided spinal anesthesia using the SonixGPS ultrasound
      guidance system: a feasibility study.
AB  - BACKGROUND: Real-time ultrasound-guided neuraxial blockade remains a largely
      experimental technique. SonixGPS(r) is a new needle tracking system that displays
      needle tip position on the ultrasound screen. We investigated if this novel
      technology might aid performance of real-time ultrasound-guided spinal
      anesthesia. METHODS: Twenty patients with body mass index < 35 kg/m(2) undergoing
      elective total joint arthroplasty under spinal anesthesia were recruited.
      Patients with previous back surgery and spinal abnormalities were excluded.
      Following a pre-procedural ultrasound scan, a 17G proprietary needle-sensor
      assembly was inserted in-plane to the transducer in four patients and out-of
      plane in 16 patients. In both approaches, the trajectory of insertion was
      adjusted in real-time until the needle tip lay just superficial to the ligamentum
      flavum-dura mater complex. At this point, a 25G 120 mm Whitacre spinal needle was
      inserted through the 17G SonixGPS(r) needle. Successful dural puncture was
      confirmed by backflow of cerebrospinal fluid from the spinal needle. RESULTS: An
      overall success rate of 14/20 (70%) was seen with two failures (50%) and four
      failures (25%) in the in-plane and out-of-plane groups respectively. Dural
      puncture was successful on the first skin puncture in 71% of patients and in a
      single needle pass in 57% of patients. The median total procedure time was 16.4
      and 11.1 min in the in-plane and out-of-plane groups respectively. CONCLUSION:
      The SonixGPS(r) system simplifies real-time ultrasound-guided spinal anesthesia
      to a large extent, especially the out-of-plane approach. Nevertheless, it remains
      a complex multi-step procedure that requires time, specialized equipment, and a
      working knowledge of spinal sonoanatomy.

PMID- 24943308
TI  - 'Complex' but coping: experience of symptoms of tuberculosis and health care
      seeking behaviours--a qualitative interview study of urban risk groups, London,
      UK.
AB  - BACKGROUND: Tuberculosis awareness, grounded in social cognition models of health
      care seeking behaviour, relies on the ability of individuals to recognise
      symptoms, assess their risk and access health care (passive case finding). There
      is scant published research into the health actions of 'hard-to-reach' groups
      with tuberculosis, who represent approximately 17% of the London TB caseload.
      This study aimed to analyse patients' knowledge of tuberculosis, their
      experiences of symptoms and their health care seeking behaviours. METHODS:
      Qualitative interviews were conducted with 17 participants, predominantly
      homeless and attending a major tuberculosis centre in London, UK. Most had
      complex medical and social needs including drug and alcohol use or immigration
      problems affecting entitlement to social welfare. Analytical frameworks aimed to
      reflect the role of broader social structures in shaping individual health
      actions. RESULTS: Although participants demonstrated some knowledge of
      tuberculosis their awareness of personal risk was low. Symptoms commonly
      associated with tuberculosis were either not recognised or were attributed to
      other causes for which participants would not ordinarily seek health care. Many
      accessed health care by chance and, for some, for health concerns other than
      tuberculosis. CONCLUSIONS: Health education, based on increasing awareness of
      symptoms, may play a limited role in tuberculosis care for populations with
      complex health and social needs. The findings support the intensification of
      outreach initiatives to identify groups at risk of tuberculosis and the
      development of structured care pathways which support people into prompt
      diagnosis and treatment.

PMID- 24943309
TI  - Periorbital subcutaneous emphysema mistaken for unilateral angioedema during
      dental crown preparation.

PMID- 24943311
TI  - Affinity purification of heme-tagged proteins.
AB  - Protein affinity purification techniques are widely used for isolating pure
      target proteins for biochemical and structural characterization. Herein, we
      describe the protocol for affinity-based purification of proteins expressed in
      Escherichia coli that uses the coordination of a peptide tag covalently modified
      with heme c, known as a heme-tag, to an L-histidine immobilized Sepharose resin.
      This approach provides an affinity purification tag visible to the eye,
      facilitating tracking of the protein. In addition, we describe methods for
      specifically detecting heme-tagged proteins in SDS-PAGE gels using a heme
      staining procedure and for quantifying the proteins using a pyridine hemochrome
      assay. 

PMID- 24943310
TI  - 1D4: a versatile epitope tag for the purification and characterization of
      expressed membrane and soluble proteins.
AB  - Incorporation of short epitope tags into proteins for recognition by commercially
      available monoclonal or polyclonal antibodies has greatly facilitated the
      detection, characterization, localization, and purification of heterologously
      expressed proteins for structure-function studies. A number of tags have been
      developed, but many epitope-antibody combinations do not work effectively for all
      immunochemical techniques due to the nature of the tag and the specificity of the
      antibodies. A highly versatile, multipurpose epitope tag is the 9 amino acid C
      terminal 1D4 peptide. This peptide tag together with the Rho1D4 monoclonal
      antibody can be used to detect proteins in complex mixtures by western blotting
      and ELISA assays, localize proteins in cells by immunofluorescence and
      immunoelectron microscopic labeling techniques, identify subunits and interacting
      proteins by co-immunoprecipitation, and purify functionally active proteins
      including membrane proteins by immunoaffinity chromatography. In this chapter we
      describe various immunochemical procedures which can be used for the detection,
      purification and localization of 1D4-tagged proteins for structure-function
      studies. 

PMID- 24943312
TI  - Purification of a recombinant protein with cellulose-binding module 3 as the
      affinity tag.
AB  - Easy-to-perform and low-cost protein purification methods are in high demand for
      the mass production of commonly used enzymes that play an important role in
      bioeconomy. A low-cost and rapid recombinant protein purification system was
      developed using CBM3 (family 3 cellulose-binding module) as affinity tag. This
      protocol describes the purification of CBM3-fusion protein and tag-free protein
      expressed in Pichia pastoris using CBM3 as an affinity tag.

PMID- 24943313
TI  - Purification of E. coli proteins using a self-cleaving chitin-binding affinity
      tag.
AB  - The use of affinity tags to purify recombinant proteins is ubiquitous in
      molecular biology. However, tag removal after purification still remains a
      challenge. The most commonly used method, proteolytic digestion, has several
      drawbacks that make the process complex and costly. One alternative to the use of
      proteolytic digestion is the use of self-cleaving purification tags. Here, we
      describe a system that combines a chitin-binding domain (CBD) tag with the ?I-CM
      intein to yield a self-cleaving purification tag. A protein gene of interest is
      genetically fused downstream of the tag, generating a fusion protein that can be
      rapidly and easily purified using a chitin resin. Intein self-cleavage is then
      induced by a simple pH and temperature shift, liberating the free target protein.
      This system can be used to readily purify any recombinant protein that can be
      expressed in E. coli, and has the potential to be applied to a wide variety of
      additional tags and expression hosts.

PMID- 24943314
TI  - Simplified protein purification using an autoprocessing, inducible enzyme tag.
AB  - The development of affinity tags has greatly simplified protein purification
      procedures. A variety of affinity tags are now available to improve expression,
      solubility, and/or tag removal. In this chapter, we describe a method for
      purifying recombinant proteins expressed in Escherichia coli that uses a highly
      specific, inducible, C-terminal autoprocessing protease tag. This method
      streamlines affinity purification, cleavage, and tag separation into a one-step
      purification procedure, avoiding the need to remove fusion tags from target
      proteins with exogenous proteases. In addition to accelerating protein
      purification, we show that this method can enhance the expression, stability, and
      solubility of select proteins. 

PMID- 24943315
TI  - SUMO as a solubility tag and in vivo cleavage of SUMO fusion proteins with Ulp1.
AB  - Expression of proteins in E. coli is often plagued by insolubility of the protein
      of interest. A solution to this problem is the expression of proteins as fusions
      to solubility tags such as the SUMO protein. SUMO fusion proteins can be cleaved
      to remove the SUMO moiety using SUMO-specific proteases such as Ulp1. Here, we
      describe the use of vectors for the expression of recombinant proteins in E. coli
      as fusions to the Drosophila SUMO protein. This includes a vector that encodes
      not only the SUMO tagged protein of interest but also SUMO-tagged Ulp1.
      Coexpression of these two proteins results in the in vivo cleavage of the protein
      of interest from the SUMO tag, while still leaving the protein of interest in a
      form that can be purified from a soluble cell lysate by nickel affinity
      chromatography.

PMID- 24943316
TI  - Rescuing aggregation-prone proteins in Escherichia coli with a dual His6-MBP tag.
AB  - Insolubility of recombinant proteins in Escherichia coli is a major impediment to
      their production for structural and functional studies. One way around this
      problem is to fuse an aggregation-prone protein to a highly soluble partner. E.
      coli maltose-binding protein (MBP) is widely recognized as a premier solubilizing
      agent. In this chapter, we describe how to construct dual His6-MBP-tagged fusion
      proteins by Gateway((r)) recombinational cloning and how to predict their yield
      and solubility. We also describe a simple and rapid procedure to test the ability
      of a His6-MBP fusion protein to bind to Ni-NTA resin and to be digested by
      tobacco etch virus (TEV) protease, along with a method to assess the solubility
      of the target protein after it has been separated from His6-MBP. 

PMID- 24943317
TI  - Expression, purification, and immobilization of recombinant tamavidin 2 fusion
      proteins.
AB  - Tamavidin 2 is a fungal avidin-like protein that binds biotin with high affinity.
      Unlike avidin or streptavidin, tamavidin 2 in soluble form is produced at high
      levels in Escherichia coli. In this chapter, we describe a method for
      immobilization and purification of recombinant proteins with the use of tamavidin
      2 as an affinity tag. The protein fused to tamavidin 2 is tightly immobilized and
      simultaneously purified on biotinylated magnetic microbeads without loss of
      activity. 

PMID- 24943318
TI  - Use of tandem affinity chromatography for purification of cannabinoid receptor
      CB2.
AB  - Tandem affinity purification has been increasingly applied to isolation of
      recombinant proteins. It relies on two consecutive chromatographic steps that
      take advantage of the affinity tags placed at opposing ends of the target
      protein. This allows for efficient removal of contaminating proteins, including
      products of proteolytic degradation of the fusion that lack either N- or C
      terminal tags. Here, we describe the use of two small affinity tags, a poly
      histidine tag and a Strep-tag for expression and purification of the human
      cannabinoid receptor CB2, an integral membrane G protein-coupled receptor. 

PMID- 24943319
TI  - Detection of protein-protein interactions using tandem affinity purification.
AB  - Tandem affinity purification (TAP) is an invaluable technique for identifying
      interaction partners for an affinity tagged bait protein. The approach relies on
      the fusion of dual tags to the bait before separate rounds of affinity
      purification and precipitation. Frequently two specific elution steps are also
      performed to increase the specificity of the overall technique. In the method
      detailed here, the two tags used are protein G and a short streptavidin binding
      peptide; however, many variations can be employed. In our example the tags are
      separated by a cleavable tobacco etch virus protease target sequence, allowing
      for specific elution after the first round of affinity purification. Proteins
      isolated after the final elution step in this process are concentrated before
      being identified by mass spectrometry. The use of dual affinity tags and specific
      elution in this technique dramatically increases both the specificity and
      stringency of the pull-downs, ensuring a low level of background nonspecific
      interactions. 

PMID- 24943320
TI  - An improved in vivo biotinylation strategy combined with FLAG and antibody based
      approaches for affinity purification of protein complexes in mouse embryonic stem
      cells.
AB  - The proteome in mouse embryonic stem cells has not been extensively studied in
      comparison to other cellular systems, limiting our understanding of multi-protein
      complex functions in stem cell biology. Several affinity purification techniques
      followed by mass spectrometry analysis have been designed and validated to
      identify protein-protein interaction networks. One such approach relies on in
      vivo biotinylation of a protein of interest and subsequent pull-down of its
      interacting partners using streptavidin-conjugated agarose beads. This technique
      takes advantage of the high affinity between biotin and streptavidin, allowing
      for high affinity purification of protein complexes without the use of
      antibodies. Here, we describe an improved large-scale purification of multi
      protein complexes in mouse embryonic stem cells by in vivo biotinylation,
      complemented with standard antibody and/or FLAG based affinity captures. This
      combined strategy benefits from the high efficiency of the streptavidin pull-down
      and the validation of the most highly confident interacting partners through the
      two alternative approaches. 

PMID- 24943321
TI  - Purification of recombinant proteins with a multifunctional GFP tag.
AB  - Green fluorescent protein (GFP) is the most widespread fluorescent reporter for
      cellular localization and interaction of proteins. Because GFP itself is not the
      protein purification tag, protein purification is generally carried out with the
      aid of additional affinity tags. We have recently engineered a "multifunctional
      GFP" (mfGFP), a variant of enhanced GFP (EGFP), in which multiple affinity tags
      are inserted in tandem into an internal loop of EGFP. The mfGFP can be used as a
      fluorescent reporter and an affinity tag, and is compatible with various
      expression systems in prokaryotic and eukaryotic cells. Herein, we describe
      detailed procedures for the expression and purification of mfGFP fusion proteins
      in mammalian cells. A method for tandem affinity purification using two different
      tags within mfGFP is also described.

PMID- 24943322
TI  - Targeted purification of SnAvi-tagged proteins.
AB  - Tandem affinity purification (TAP) is a powerful technique to identify protein
      complex members. The modular composition of TAP-tags allows two sequential
      protein enrichment steps and thereby drastically reduces the amount of
      contaminants. Here, we describe the application of the SnAvi-tag-a TAP-tag useful
      in different expression systems. Due to its modular composition, this tag is
      multifunctional and facilitates among others the in vivo visualization of tagged
      proteins and their cell type specific activation.

PMID- 24943323
TI  - An efficient fluorescent protein-based multifunctional affinity purification
      approach in mammalian cells.
AB  - Knowledge of an individual protein's modifications, binding partners, and
      localization is essential for understanding complex biological networks. We
      recently described a fluorescent protein-based (mVenus) multifunctional affinity
      purification (MAP) tag that can be used both to purify a given protein and
      determine its localization (Ma et al., Mol Cell Proteomics 11:501-511, 2012). MAP
      purified protein complexes can be further analyzed to identify binding partners
      and posttranslational modifications by LC-MS/MS. The MAP approach offers rapid
      FACS-selection of stable clonal cell lines based on the expression
      level/fluorescence of the MAP-protein fusion. The MAP tag is highly efficient and
      shows little variability between proteins. Here we describe the general MAP
      purification method in detail, and show how it can be applied to a specific
      protein using the human Cdc14B phosphatase as an example. 

PMID- 24943324
TI  - Bimolecular affinity purification: a variation of TAP with multiple applications.
AB  - The identification of true interacting partners of any given bait can be plagued
      by the nonspecific purification of irrelevant proteins. To avoid this problem,
      Tandem Affinity Purification (TAP) is a widely used procedure in molecular
      biology as this reduces the chance of nonspecific proteins being present in the
      final preparation. In this approach, two different affinity tags are fused to the
      protein bait. Herein, we review in detail a variation on the TAP procedure that
      we have previously developed, where the affinity moieties are placed on two
      different proteins that form a complex in vivo. This variation, which we refer to
      as Bimolecular Affinity Purification (BAP), is suited for the identification of
      specific molecular complexes marked by the presence of two known proteins. We
      have utilized BAP for characterization of molecular complexes and evaluation of
      proteins interaction. Another application of BAP is the isolation of ubiquitin
      like proteins (UBL)-modified fractions of a given protein and characterization of
      the lysine-acceptor site and structure of UBL-chains. 

PMID- 24943325
TI  - Cat-scratch-disease-associated macular oedema treated with intravitreal
      ranibizumab.

PMID- 24943327
TI  - Exploration of chemically cross-linked metal-organic frameworks.
AB  - A series of geometrically constrained, cross-linked benzene dicarboxylic acid
      (bdc) derivatives have been synthesized and incorporated into the canonical
      isoreticular metal-organic framework (IRMOF) lattice. Only certain cross-links,
      which allow for the proper relative orientation of the bdc subunits, form the
      desired IRMOF. Design criteria from these cross-linked ligands allowed for the
      rational design of two oligomeric ligands composed of three bdc monomers tethered
      together. These oligomeric ligands were also readily incorporated into an IRMOF
      lattice with a high degree of crystallinity and porosity, providing a new
      dimension to rational ligand design for metal-organic frameworks. 

PMID- 24943326
TI  - Altered gene expression and spine density in nucleus accumbens of adolescent and
      adult male mice exposed to emotional and physical stress.
AB  - Stressful early life experiences are implicated in lifelong health. However,
      little is known about the consequences of emotional stress (ES) or physical
      stress (PS) on neurobiology. Therefore, the following set of experiments was
      designed to assess changes in transcription and translation of key proteins
      within the nucleus accumbens (NAc). Male adolescent (postnatal day 35) or adult
      (8-week-old) mice were exposed to ES or PS using a witness social defeat
      paradigm. Then, 24 h after the last stress session, we measured levels of
      specific mRNAs and proteins within the NAc. Spine density was also assessed in
      separate groups of mice. Exposure to ES or PS disrupted extracellular signal
      related kinase 2 (ERK2), reduced transcription of DeltaFosB and had no effect on
      cAMP response element-binding protein (CREB) mRNA. Western blots revealed that
      exposure to ES or PS decreased ERK2 phosphorylation in adolescents, whereas the
      same stress regimen increased ERK2 phosphorylation in adults. Exposure to ES or
      PS had no effect on DeltaFosB or CREB phosphorylation. ES and PS increased spine
      density in the NAc of adolescent exposed mice, but only exposure to PS increased
      spine density in adults. Together, these findings demonstrate that exposure to ES
      or PS is a potent stressor in adolescent and adult mice and can disturb the
      integrity of the NAc by altering transcription and translation of important
      signaling molecules in an age-dependent manner. Furthermore, exposure to ES and
      PS induces substantial synaptic plasticity of the NAc.

PMID- 24943328
TI  - Facilitators and barriers to cervical cancer screening, diagnosis, and enrollment
      in Medicaid: experiences of Georgia's Women's Health Medicaid Program enrollees.
AB  - Although cervical cancer incidence and mortality rates have declined in the USA,
      African American women have a higher incidence rate of cervical cancer and a
      higher percentage of late-stage diagnosis than white women. Previous analyses by
      the authors showed that, even after adjusting for age, provider location, and
      availability, African American women were almost half as likely as white women to
      be diagnosed or enter Medicaid while at an early stage of their cervical cancer.
      To understand why these differences exist, we undertook a qualitative examination
      of the cervical cancer experiences of women enrolled in Georgia's Women's Health
      Medicaid Program (WHMP). Life history interviews were conducted with 24 WHMP
      enrollees to understand what factors shaped their cervical cancer experiences,
      from screening through enrollment in Medicaid. We also examined whether these
      factors differed by race in order to identify opportunities for increasing
      awareness of cervical cancer screening among underserved women. Results suggest
      that many women, especially African Americans, lacked understanding and
      recognition of early symptoms of cervical cancer, which prevented them from
      receiving a timely diagnosis. Additionally, participants responded positively to
      provider support and good communication but wished that their doctors explained
      their diagnosis more clearly. Finally, women were able to enroll in Medicaid
      without difficulty due largely to the assistance of clinical staff. These
      findings support the need to strengthen provider education and public health
      efforts to reach low-income and minority communities for screening and early
      detection of cervical cancer. 

PMID- 24943329
TI  - Systematic review with meta-analysis: alcohol consumption and the risk of
      colorectal adenoma.
AB  - BACKGROUND: Studies on the relation between alcohol consumption and risk of
      colorectal adenoma (CRA), a precursor of colorectal cancer, have been
      inconsistent. AIM: A systematic review with meta-analysis was conducted to
      investigate the association and the dose-response of alcohol with CRA. METHODS: A
      literature search was performed on PubMed to identify relevant studies published
      up to January 2014. A fixed or random effects model was used to estimate
      summarised relative risks (RRs) and 95% confidence intervals (CIs) for the
      association between alcohol intake and CRA risk. Statistical heterogeneity
      between studies was assessed with the chi(2) statistic and quantified by I2.
      RESULTS: Twenty-three case-control studies and two cohort studies were included
      in the meta-analysis. All drinkers were associated with 17% increased risk for
      CRA, compared with nondrinkers or occasional alcohol drinkers. The dose-response
      analysis demonstrated that for drinkers of 10, 25, 50 and 100 g/day alcohol
      consumption, the estimated RRs of CRA were 1.02 (95% CI 0.89-1.16), 1.06 (95% CI
      0.92-1.20), 1.16 (95% CI 1.02-1.33) and 1.61 (95% CI 1.42-1.84) respectively, in
      comparison with non-/occasional drinkers. The risks were consistent in the
      subgroup analyses of gender and site of adenoma, while it was stronger in
      European studies than the studies in the US and Asia. CONCLUSIONS: This study
      suggests that alcohol intake is related to a significant increase of risk for
      colrectal adenoma.

PMID- 24943331
TI  - Clinical impact of systematically performing autopsies following selective
      termination of pregnancies: comparison between multiples and singletons.
AB  - INTRODUCTION: The aim of this study was to evaluate the clinical impact of
      systematically performing autopsies following selective termination of pregnancy.
      MATERIAL AND METHODS: A retrospective study of necropsies following medical
      termination of pregnancy performed in a tertiary referral hospital. A correlation
      between prenatal diagnosis and postmortem findings was performed. The cases were
      classified as having complete agreement, complete disagreement or major agreement
      with additional information. A comparison between multiples (n = 29) and
      singletons (n = 374) was undertaken. RESULTS: The median gestational age at the
      time of termination/selective feticide was 19 (11-34) weeks in multiples and 18
      (6-36) weeks in singletons (p = 0.190). In 5 cases (17.2%) of multiples (50.0%
      submitted to selective feticide) fetal autopsy was not possible, while in
      singletons autopsy was not feasible in only 1.3% (p < 0.005). DISCUSSION:
      Contrarily to singleton pregnancies, in twin pregnancies with termination of 1
      fetus it should not be possible to undertake an autopsy. When a selective
      termination is performed away from delivery, the time of retention may hinder the
      feasibility of the necropsy study. In those cases, it is crucial to make an
      exhaustive investigation previously to selective feticide.

PMID- 24943330
TI  - Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic
      airways disease.
AB  - BACKGROUND: Associations between vitamin D status and childhood asthma are
      increasingly reported, but direct causation and mechanisms underlying an effect
      remain unknown. We investigated the effect of early-life vitamin D deficiency on
      the development of murine neonatal allergic airways disease (AAD). METHODS: In
      utero and early-life vitamin D deficiency was achieved using a vitamin D
      deficient diet for female mice during the third trimester of pregnancy and
      lactation. Offspring were weaned onto a vitamin D-deficient or vitamin D-replete
      diet, and exposure to intranasal house dust mite (HDM) or saline was commenced
      from day 3 of life for up to 6 weeks, when airway hyper-responsiveness (AHR),
      airway inflammation and remodelling were assessed. RESULTS: Neonatal mice that
      had in utero and early-life vitamin D deficiency had significantly increased
      pulmonary CD3(+) CD4(+) T1ST2(+) cells and reduced CD4(+) IL-10(+) cells. This
      effect was enhanced following HDM exposure. AHR in HDM-exposed mice was
      unaffected by vitamin D status. Introduction of vitamin D into the diet at
      weaning resulted in a significant reduction in serum IgE levels, reduced
      pulmonary eosinophilia and peri-bronchiolar collagen deposition. CONCLUSION: Peri
      natal vitamin D deficiency alone has immunomodulatory effects including Th2
      skewing and reduced IL-10-secreting T regulatory cells, exaggerated with
      additional allergen exposure. Vitamin D deficiency in early life does not affect
      AHR, but contributes to disease severity with worse eosinophilic inflammation and
      airway remodelling. Importantly, supplementation with vitamin D improves both of
      these pathological abnormalities.

PMID- 24943333
TI  - The EAN: a new hope for European integration.

PMID- 24943332
TI  - When is surgery required for the treatment of biliary complications after
      pediatric liver transplantation?

PMID- 24943334
TI  - Genome-wide association study in FTD: divide to conquer.

PMID- 24943336
TI  - Neurodevelopmental toxicity: still more questions than answers.

PMID- 24943335
TI  - Neurodevelopmental toxicity: still more questions than answers.

PMID- 24943337
TI  - Neurodevelopmental toxicity: still more questions than answers.

PMID- 24943338
TI  - Neurodevelopmental toxicity: still more questions than answers.

PMID- 24943339
TI  - Neurodevelopmental toxicity: still more questions than answers--authors'
      response.

PMID- 24943340
TI  - Evidence or clinical implementation: which should come first?

PMID- 24943341
TI  - Polio-like disease in the news: much ado about nothing?

PMID- 24943342
TI  - Preventing polio.

PMID- 24943345
TI  - Occasional seizures, epilepsy, and inborn errors of metabolism.
AB  - Seizures are a common paediatric problem, with inborn errors of metabolism being
      a rare underlying aetiology. The clinical presentation of inborn errors of
      metabolism is often associated with other neurological symptoms, such as
      hypotonia, movement disorders, and cognitive disturbances. However, the
      occurrence of epilepsy associated with inborn errors of metabolism represents a
      major challenge that needs to be identified quickly; for some cases, specific
      treatments are available, metabolic decompensation might be avoided, and accurate
      counselling can be given about recurrence risk. Some clinical presentations are
      more likely than others to point to an inborn error of metabolism as the cause of
      seizures. Knowledge of important findings at examination, and appropriate
      biochemical investigation of children with seizures of uncertain cause, can aid
      the diagnosis of an inborn error of metabolism and ascertain whether or not the
      seizures are amenable to specific metabolic treatment. 

PMID- 24943346
TI  - Balo's concentric sclerosis.
AB  - Balo's concentric sclerosis is often regarded as a rare variant of multiple
      sclerosis. Patients with this disorder present with acute or subacute
      neurological deterioration, with MRI showing one or more concentrically
      multilayered ring-like lesions usually in the cerebral white matter.
      Historically, Balo's concentric sclerosis was thought fatal in all cases.
      However, the availability of MRI has led to a better appreciation of the variable
      natural history of patients presenting with radiologically evident Balo lesions
      and the clinical association with multiple sclerosis and, less often, with other
      neurological disorders. Important advances have increased understanding of the
      immunopathogenic mechanisms associated with the formation of Balo lesions.
      However, how to treat an acute lesion and when or whether to start treatment are
      less well understood, although for patients with Balo lesions who also fulfil
      standard diagnostic criteria for multiple sclerosis, our opinion is that
      treatment with multiple sclerosis disease-modifying therapy would seem
      reasonable. 

PMID- 24943347
TI  - Pharmacokinetics, pulmonary disposition and tolerability of liposomal gentamicin
      and free gentamicin in foals.
AB  - REASONS FOR PERFORMING THE STUDY: Although gentamicin is highly active against
      Rhodococcus equi in vitro, its clinical efficacy has been limited presumably due
      to poor cellular uptake. Encapsulation of drugs in liposomes enhances their
      cellular uptake. OBJECTIVES: To compare the disposition of liposomal gentamicin
      (LG) and free gentamicin (FG) in the plasma, pulmonary epithelial lining fluid
      and bronchoalveolar cells of healthy foals after i.v. administration or by
      nebulisation, and to assess the tolerability of the drug after repeated i.v.
      dosing. STUDY DESIGN: Experimental study. METHODS: Eight healthy foals received a
      single i.v. or nebulised dose (6.6 mg/kg bwt) of LG or FG in a balanced Latin
      square design, with a 14-day washout period between treatments. Subsequently, 12
      healthy foals were given either LG or FG at 6.6 mg/kg bwt i.v. q. 24 h for 7
      doses and urinary protein, creatinine, gamma-glutamyltransferase and electrolytes
      were measured on Days 0, 3 and 7 to quantify renal injury. Concentrations of
      gentamicin were measured using liquid chromatography-tandem mass spectrometry.
      RESULTS: After i.v. administration, LG had a significantly higher mean (+/- s.d.)
      half-life (16.3 +/- 3.5 vs. 6.2 +/- 1.8 h) and volume of distribution (2.00 +/-
      1.03 vs. 0.72 +/- 0.32 l/kg bwt) compared with FG. Peak gentamicin concentrations
      in bronchoalveolar cells were significantly higher for LG compared with FG after
      administration by both the i.v. (5.27 +/- 2.67 vs. 2.98 +/- 1.67 mg/l) and the
      nebulised (4.47 +/- 2.66 vs. 1.49 +/- 0.57 mg/l) routes. Liposomal gentamicin was
      well tolerated by all foals and indices of renal injury were not significantly
      different from those of foals administered FG. CONCLUSIONS: Administration of LG
      is well tolerated and results in higher intracellular drug concentrations than
      FG. Liposomal gentamicin warrants further investigation for the treatment of
      infections caused by intracellular pathogens such as Rhodococcus equi.

PMID- 24943348
TI  - Increased immunoreactivity of cathepsins in the rat esophagus under chronic acid
      reflux esophagitis.
AB  - We have designed a stable rat chronic acid reflux esophagitis (RE) model. In
      gastrointestinal lesions, several lysosomal cathepsins are known to participate
      in epithelial permeability in cell-cell connections, such as tight junctions in
      ulcerative colitis. However, very few studies have focused on the distribution of
      cathepsins in the esophageal multilayer squamous epithelium. Therefore to clarify
      the role of cathepsins in RE, we investigated their immunohistological
      localization in the esophageal epithelium under normal conditions and after RE.
      Of the cathepsins examined (cathepsins B, C, D, F, H, L, S, and X), granular
      immunoreactivity for cathepsins B, C, D and L was observed in the control
      esophageal epithelia; although, their distribution differed depending on the
      enzyme examined. In the RE model, immunoreactivity of these cathepsins was
      increased in esophageal epithelial cells and activated macrophages. The
      immunoreactivity for cathepsins F, H, S and X was barely detectable in the
      control esophageal epithelium. However, in the RE model, we noticed a slight
      increase in the expression of cathepsins H and X in the epithelial cells.
      Furthermore, activated macrophages of the RE model possessed intense
      immunoreactivity for these cathepsins, which may have been related to esophageal
      inflammatory mechanisms. 

PMID- 24943350
TI  - Protective effect of recombinant human brain natriuretic peptide on acute renal
      injury induced by endotoxin in canines.
AB  - The objective of this study was to evaluate the protective effect of recombinant
      human brain natriuretic peptide (rhBNP) on endotoxin-induced acute kidney injury
      (AKI) in canine model of septic shock and its potential mechanisms. Dogs with
      endotoxin-induced septic shock were subjected to intravenous infusion of saline
      solution or rhBNP at the concentrations of 5 MUg/kg (low-dose intervention group)
      or 10 MUg/kg (high-dose intervention group). At 0, 2, 4, 8, and 12 h, the
      systemic vascular resistance index (SVRI) as well as serum levels of high
      mobility group box 1 protein (HMGB-1) and creatinine were measured, and kidney
      tissue samples were taken for histological examination. We have found that low
      and high doses of rhBNP could significantly reduce kidney tissue damage, such as
      tubular epithelial swelling and atrophy, and interstitial cell swelling in
      response to LPS injection in the dog sepsis models. rhBNP administration
      significantly reduced SVRI and serum levels of creatinine in dogs with LPS
      induced sepsis in a dose-dependent manner, and attenuated the rise in the
      circulating HMGB-1. In conclusion, these findings suggest that rhBNP may exert
      dose-dependent protective effect on kidney tissue with endotoxin-induced injury,
      and this effect may be associated with the changes in blood levels of HMGB-1.
      rhBNP may be considered as therapeutic agents for treating sepsis-induced AKI.

PMID- 24943351
TI  - A simple PCR-based marker to determine sex in aspen.
AB  - The genus Populus features a genetically controlled sex determination system,
      located on chromosome 19. However, different Populus species vary in the position
      of the sex-linked region on the respective chromosome and the apparent
      heterogametic sex, and the precise mechanism of sex determination in Populus is
      still unknown. Using next generation sequencing of pooled samples of male and
      female aspens, we identified the aspen homologue of the P. trichocarpa gene
      Potri.019G047300 ('TOZ19') to be male-specific. While in P. tremuloides, the
      complete gene is missing in the genome of female plants, a short fragment of the
      3'-part of the gene is still present in P. tremula females. The male-specific
      presence and transcription of TOZ19 was further verified using PCR in various
      different aspen individuals and RT-PCR expression analysis. TOZ19 is potentially
      involved in early steps of flower development, and represents an interesting
      candidate gene for involvement in sex determination in aspen. Regardless of its
      role as candidate gene, TOZ19 represents an ideal marker for determination of the
      sex of non-flowering aspen individuals or seedlings. 

PMID- 24943349
TI  - Whole genome sequencing reveals potential targets for therapy in patients with
      refractory KRAS mutated metastatic colorectal cancer.
AB  - BACKGROUND: The outcome of patients with metastatic colorectal carcinoma (mCRC)
      following first line therapy is poor, with median survival of less than one year.
      The purpose of this study was to identify candidate therapeutically targetable
      somatic events in mCRC patient samples by whole genome sequencing (WGS), so as to
      obtain targeted treatment strategies for individual patients. METHODS: Four
      patients were recruited, all of whom had received > 2 prior therapy regimens.
      Percutaneous needle biopsies of metastases were performed with whole blood
      collection for the extraction of constitutional DNA. One tumor was not included
      in this study as the quality of tumor tissue was not sufficient for further
      analysis. WGS was performed using Illumina paired end chemistry on HiSeq2000
      sequencing systems, which yielded coverage of greater than 30X for all samples.
      NGS data were processed and analyzed to detect somatic genomic alterations
      including point mutations, indels, copy number alterations, translocations and
      rearrangements. RESULTS: All 3 tumor samples had KRAS mutations, while 2 tumors
      contained mutations in the APC gene and the PIK3CA gene. Although we did not
      identify a TCF7L2-VTI1A translocation, we did detect a TCF7L2 mutation in one
      tumor. Among the other interesting mutated genes was INPPL1, an important gene
      involved in PI3 kinase signaling. Functional studies demonstrated that inhibition
      of INPPL1 reduced growth of CRC cells, suggesting that INPPL1 may promote growth
      in CRC. CONCLUSIONS: Our study further supports potential molecularly defined
      therapeutic contexts that might provide insights into treatment strategies for
      refractory mCRC. New insights into the role of INPPL1 in colon tumor cell growth
      have also been identified. Continued development of appropriate targeted agents
      towards specific events may be warranted to help improve outcomes in CRC.

PMID- 24943352
TI  - Food security and nutrition interventions in response to the AIDS epidemic:
      assessing global action and evidence.
AB  - The number of people receiving antiretroviral therapy in developing countries has
      increased dramatically. The last decade has brought an increased understanding of
      the interconnectedness between HIV/AIDS, food insecurity, and undernutrition and
      a surge of evidence on how to address the food security and nutrition dimensions
      of the epidemic. We review this evidence as well as the corresponding evolution
      of policy support for incorporating food security and nutrition concerns into HIV
      programming. The available evidence, although varied in scope and methodologies,
      shows that nutrition supplementation and safety nets in the form of food
      assistance and livelihood interventions have potential in certain contexts to
      improve food security and nutrition outcomes in an HIV/AIDS context. In the face
      of funding uncertainties and competing priorities, we must maintain momentum
      towards effective and sustainable solutions to the epidemic through continued
      systematic research to inform policy and through the strengthening of monitoring
      systems to dynamically inform intervention development. 

PMID- 24943353
TI  - The BMJ statins papers misrepresent the facts.

PMID- 24943344
TI  - Frontotemporal dementia and its subtypes: a genome-wide association study.
AB  - BACKGROUND: Frontotemporal dementia (FTD) is a complex disorder characterised by
      a broad range of clinical manifestations, differential pathological signatures,
      and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have
      been associated with FTD. We sought to identify novel genetic risk loci
      associated with the disorder. METHODS: We did a two-stage genome-wide association
      study on clinical FTD, analysing samples from 3526 patients with FTD and 9402
      healthy controls. To reduce genetic heterogeneity, all participants were of
      European ancestry. In the discovery phase (samples from 2154 patients with FTD
      and 4308 controls), we did separate association analyses for each FTD subtype
      (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and
      FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis
      of the entire dataset. We carried forward replication of the novel suggestive
      loci in an independent sample series (samples from 1372 patients and 5094
      controls) and then did joint phase and brain expression and methylation
      quantitative trait loci analyses for the associated (p<5 * 10(-8)) single
      nucleotide polymorphisms. FINDINGS: We identified novel associations exceeding
      the genome-wide significance threshold (p<5 * 10(-8)). Combined (joint) analyses
      of discovery and replication phases showed genome-wide significant association at
      6p21.3, HLA locus (immune system), for rs9268877 (p=1.05 * 10(-8); odds
      ratio=1.204 [95% CI 1.11-1.30]), rs9268856 (p=5.51 * 10(-9); 0.809 [0.76-0.86])
      and rs1980493 (p value=1.57 * 10(-8), 0.775 [0.69-0.86]) in the entire cohort. We
      also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the
      transcripts of which are related to lysosomal biology), for the behavioural FTD
      subtype for which joint analyses showed suggestive association for rs302668
      (p=2.44 * 10(-7); 0.814 [0.71-0.92]). Analysis of expression and methylation
      quantitative trait loci data suggested that these loci might affect expression
      and methylation in cis. INTERPRETATION: Our findings suggest that immune system
      processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to
      11q14) are potentially involved in FTD. Our findings need to be replicated to
      better define the association of the newly identified loci with disease and to
      shed light on the pathomechanisms contributing to FTD. FUNDING: The National
      Institute of Neurological Disorders and Stroke and National Institute on Aging,
      the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and
      Texas Tech University Health Sciences Center.

PMID- 24943355
TI  - Parental perceptions of neighborhood environments, BMI, and active behaviors in
      girls aged 7-9 years.
AB  - OBJECTIVES: Habitual physical activity (PA) may be influenced by a broad range of
      neighborhood, school, community, and family factors. Young people, particularly
      girls, tend to show lower habitual PA than boys and should be a target for
      prevention strategies aimed at healthy lifestyles. The purpose of this study was
      twofold: (1) to determine which perceived attributes about neighborhoods are
      related to active behaviors; (2) to analyze which perceived attributes about
      neighborhoods are related to body mass index (BMI) of children. METHODS: The
      sample was comprised of 1,886 girls aged 7-9 years. Height and weight were
      measured, and BMI was calculated subsequently. Participants were classified as
      normal weight or overweight/obese (Cole et al. [2000]: BMJ 320: 1240-1243).
      Environmental variables and physical activities were assessed by questionnaire
      filled out by their parents-the Environmental Module of the International
      Physical Activity Prevalence Study (IPS, 2002) was used. Multiple linear
      regressions, with adjustments for confounding variables, were used. RESULTS: Data
      revealed that neighborhoods with recreational facilities and infrastructure for
      walking and cycling were predictors of active behaviors; neighborhood safety was
      an additional related factor of habitual PA. On the other hand, neighbors with
      better access to destinations and with interesting things to look at while
      walking were significantly associated with lower BMI in Portuguese children.
      CONCLUSION: The study found some significant relationships between parental
      perceptions of the environment and BMI and habitual PA of Portuguese girls,
      especially related to security for walking and unpleasant neighborhoods, and
      access to destinations.

PMID- 24943354
TI  - Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk for
      herpes zoster (HZ) (i.e., shingles). The aim of this study was to determine
      whether treatment with tofacitinib increases the risk of HZ in patients with RA.
      METHODS: HZ cases were identified as those reported by trial investigators from
      the databases of the phase II, phase III, and long-term extension (LTE) clinical
      trials in the Tofacitinib RA Development Program. Crude incidence rates (IRs) of
      HZ per 100 patient-years (with 95% confidence intervals [95% CIs]) were
      calculated by exposure group. Logistic regression analyses were performed to
      evaluate potential risk factors for HZ (e.g., age, prednisone use). RESULTS:
      Among 4,789 participants, 239 were identified as having tofacitinib-associated HZ
      during the phase II, phase III, and LTE trials, of whom 208 (87%) were female and
      whose median age was 57 years (range 21-75 years). One HZ case (0.4%) was
      multidermatomal; none of the cases involved visceral dissemination or death.
      Twenty-four patients with HZ (10%) permanently discontinued treatment with
      tofacitinib, and 16 (7%) were either hospitalized or received intravenous
      antiviral drugs. The crude HZ IR across the development program was 4.4 per 100
      patient-years (95% CI 3.8-4.9), but the IR was substantially higher within Asia
      (7.7 per 100 patient-years, 95% CI 6.4-9.3). Older age was associated with HZ
      (odds ratio 1.9, 95% CI 1.5-2.6), and IRs for HZ were similar between patients
      receiving 5 mg tofacitinib twice daily (4.4 per 100 patient-years, 95% CI 3.2
      6.0) and those receiving 10 mg twice daily (4.2 per 100 patient-years, 95% CI 3.1
      5.8). In the phase III trials among placebo recipients, the incidence of HZ was
      1.5 per 100 patient-years (95% CI 0.5-4.6). CONCLUSION: In the Tofacitinib RA
      Development Program, increased rates of HZ were observed in patients treated with
      tofacitinib compared with those receiving placebo, particularly among patients
      within Asia. Complicated HZ among tofacitinib-treated patients was rare.

PMID- 24943356
TI  - Vitamin D levels may have a role in cancer prognosis, study shows.

PMID- 24943358
TI  - Synthesis, characterization and properties of a family of lead(II)-organic
      frameworks based on a multi-functional ligand 2-amino-4-sulfobenzoic acid
      exhibiting auxiliary ligand-dependent dehydration-rehydration behaviours.
AB  - A systematic investigation is reported of the use of the multi-functional ligand
      2-amino-4-sulfobenzoate (asba(2-)) to construct lead(II)-organic frameworks in
      the presence and absence of N-donor auxiliary ligands phen, bipy and bix [phen =
      1,10-phenanthroline, bipy = 2,2'-bipyridine and bix = 1,4-(methylene
      benzene)bisimidazole]. Under ambient, aqueous conditions the assembly of asba(2-)
      with Pb(II) and phen or bipy leads to two iso-structural 2D double-layer
      frameworks, {[Pb2(asba)2(phen)2(H2O)].2H2O}n (1) and
      {[Pb2(asba)2(bipy)2(H2O)].2H2O}n (2). [Pb2(asba)2(bix)2(H2O)2]n (3) is obtained
      in the presence of the auxiliary ligand bix and possesses a 3D network built up
      from 2D Pb(II)-asba(2-)-bridged double-layer pillared by bix. A 2D (4,4)
      topological network [Pb(asba)(H2O)]n (4) is obtained in the absence of any second
      ligand or presence of some bistriazole bridging spacers. The coordination modes
      of the ligand asba(2-) in 1-4 are greatly dependent on the type of auxiliary
      ligand and the compounds exhibit auxiliary ligand-dependent dehydration
      rehydration behaviours; 1 shows in situ rapid and reversible dehydration
      rehydration behaviour in air, while the iso-structural compound 2 loses
      crystallinity in air and transforms into {[Pb2(asba)2(bipy)2(H2O)].H2O}n (2A)
      verified by TGA, elemental analysis and powder X-ray diffraction analysis (PXRD).
      3 also shows reversible dehydration-rehydration behaviour, but it takes around
      one week to rehydrate even after exposure to water vapor, while the dehydrated
      phase of 4 rehydrates to a new crystalline material. 1 and 3 fall within the
      category of the "recoverable collapsing" and "guest-induced re-formation"
      frameworks. The water molecules in 1 and 3 have some influence on their solid
      state fluorescent emission intensity.

PMID- 24943357
TI  - Import of ribosomal proteins into yeast mitochondria.
AB  - Mitochondrial ribosomes of baker's yeast contain at least 78 protein subunits.
      All but one of these proteins are nuclear-encoded, synthesized on cytosolic
      ribosomes, and imported into the matrix for biogenesis. The import of matrix
      proteins typically relies on N-terminal mitochondrial targeting sequences that
      form positively charged amphipathic helices. Interestingly, the N-terminal
      regions of many ribosomal proteins do not closely match the characteristics of
      matrix targeting sequences, suggesting that the import processes of these
      proteins might deviate to some extent from the general import route. So far, the
      biogenesis of only two ribosomal proteins, Mrpl32 and Mrp10, was studied
      experimentally and indeed showed surprising differences to the import of other
      preproteins. In this review article we summarize the current knowledge on the
      transport of proteins into the mitochondrial matrix, and thereby specifically
      focus on proteins of the mitochondrial ribosome. 

PMID- 24943360
TI  - [Driving ability with cerebral perfusion disorders].
AB  - In Germany expert testimony on driving ability requires knowledge of the
      corresponding legislation, the guidelines for expertises on driver aptitude and a
      qualification in traffic medicine. The testimony should clearly identify
      handicaps with regard to driving, give estimates on the risks of a sudden loss of
      the driving capability by stroke recurrence or epileptic seizures, and also
      consider personal attitudes, such as inadequate behaviour and lack of insight.
      Physical handicaps can often be compensated for by restraints, such as vehicle
      modifications and restrictions, such as daylight driving only.The testimony must
      also give estimates on the risks of a sudden loss of the driving capability by
      stroke recurrence or epileptic seizures. Two models are proposed by which an
      estimate of harmful traffic accidents due to stroke recurrence can be made. 

PMID- 24943359
TI  - Pilus distribution among lineages of group b streptococcus: an evolutionary and
      clinical perspective.
AB  - BACKGROUND: Group B Streptococcus (GBS) is an opportunistic pathogen in both
      humans and bovines. Epidemiological and phylogenetic analyses have found strains
      belonging to certain phylogenetic lineages to be more frequently associated with
      invasive newborn disease, asymptomatic maternal colonization, and subclinical
      bovine mastitis. Pilus structures in GBS facilitate colonization and invasion of
      host tissues and play a role in biofilm formation, though few large-scale studies
      have estimated the frequency and diversity of the three pilus islands (PIs)
      across diverse genotypes. Here, we examined the distribution of pilus islands
      (PI) 1, 2a and 2b among 295 GBS strains representing 73 multilocus sequence types
      (STs) belonging to eight clonal complexes. PCR-based RFLP was also used to
      evaluate variation in the genes encoding pilus backbone proteins of PI-2a and PI
      2b. RESULTS: All 295 strains harbored one of the PI-2 variants and most human
      derived strains contained PI-1. Bovine-derived strains lacked PI-1 and possessed
      a unique PI-2b backbone protein allele. Neonatal strains more frequently had PI-1
      and a PI-2 variant than maternal colonizing strains, and most CC-17 strains had
      PI-1 and PI-2b with a distinct backbone protein allele. Furthermore, we present
      evidence for the frequent gain and loss of genes encoding certain pilus types.
      CONCLUSIONS: These data suggest that pilus combinations impact host specificity
      and disease presentation and that diversification often involves the loss or
      acquisition of PIs. Such findings have implications for the development of GBS
      vaccines that target the three pilus islands.

PMID- 24943361
TI  - [New facts of long-term prophylaxis for bipolar affective disorder].
AB  - Lithium and with restrictions, carbamazepine, valproic acid, lamotrigine,
      olanzapine, aripiprazole and quetiapine, are approved in Germany for maintenance
      treatment of bipolar disorder. Lithium is the only drug that (I) proved to be
      effective for the prevention of depressive as well as manic episodes in state-of
      the-art studies without an enriched design and that (II) is approved for the
      maintenance treatment of bipolar disorders without restrictions. It (III) is also
      the only drug which is recommended for maintenance treatment by the current
      German S3 guidelines on bipolar disorders with the highest degree of
      recommendation (A) and (IV) is the only drug with a well proven suicide
      preventive effect. Hence, lithium is the mood stabilizer of first choice. No
      patient should be deprived of lithium without a specific reason. Side effects and
      risks are manageable if both the physician and the patient are well informed.
      Detailed and practical information on a safe use of lithium can be found in the
      S3 guidelines on bipolar disorders. For patients who do not respond sufficiently
      to lithium, have contraindications or non-tolerable side effects, other mood
      stabilizers should be used. Restrictions in their respective approval as well as
      specific side effects and risks have to be taken into account. Because
      maintenance treatment is a long-term treatment, particular concern should be paid
      to drugs with the potential risk of a metabolic syndrome, particularly atypical
      antipsychotics. 

PMID- 24943362
TI  - [Medical students' attitude towards electroconvulsive therapy: Impact of patient
      oriented training].
AB  - BACKGROUND: As a particular aspect of psychiatric clinical training many students
      instinctively harbor reservations towards the field of electroconvulsive
      treatment (ECT). In this context the question arises how controversial issues,
      such as ECT can be addressed during the placement. The clinical training is
      predestined to provide basic knowledge concerning ECT for future doctors. As
      multipliers and potential referrers they then can work to prevent severe mental
      illness from becoming chronic. MATERIALS AND METHODS: Prior to the clinical
      psychiatric teaching course 158 medical students of the RWTH Aachen University
      were randomly assigned to three groups. The first actively took part in an ECT
      therapy session (ECT group), the second was shown an educational video (video
      group) and the third served as a control group. A questionnaire was filled in
      before and after the training concerning the knowledge and the attitudes towards
      ECT. RESULTS: In the course of the clinical training the attitudes of the
      students towards ECT became more positive for all items. The willingness to agree
      to ECT in the case of patients, family members and friends and themselves
      increased in the ECT group and the video group but not in the control group. Only
      the ECT group proved to be superior to the control group in the direct
      comparisons. In both interventions the knowledge about ECT increased more in
      comparison to the control group despite the very limited interventions.
      CONCLUSION: Reservations to touch on the controversial issue of ECT during the
      clinical training do not seem to be justified. Even a single hands-on or video
      experience can have a relevant impact on knowledge and attitude towards ECT in
      medical students. This opportunity should be used more intensively.

PMID- 24943363
TI  - [Non-ketotic hyperglycemia-induced hemichorea athetosis].

PMID- 24943364
TI  - Language evolution: syntax before phonology?
AB  - Phonology and syntax represent two layers of sound combination central to
      language's expressive power. Comparative animal studies represent one approach to
      understand the origins of these combinatorial layers. Traditionally, phonology,
      where meaningless sounds form words, has been considered a simpler combination
      than syntax, and thus should be more common in animals. A linguistically informed
      review of animal call sequences demonstrates that phonology in animal vocal
      systems is rare, whereas syntax is more widespread. In the light of this and the
      absence of phonology in some languages, we hypothesize that syntax, present in
      all languages, evolved before phonology. 

PMID- 24943365
TI  - Effects of feral cats on the evolution of anti-predator behaviours in island
      reptiles: insights from an ancient introduction.
AB  - Exotic predators have driven the extinction of many island species. We examined
      impacts of feral cats on the abundance and anti-predator behaviours of Aegean
      wall lizards in the Cyclades (Greece), where cats were introduced thousands of
      years ago. We compared populations with high and low cat density on Naxos Island
      and populations on surrounding islets with no cats. Cats reduced wall lizard
      populations by half. Lizards facing greater risk from cats stayed closer to
      refuges, were more likely to shed their tails in a standardized assay, and fled
      at greater distances when approached by either a person in the field or a mounted
      cat decoy in the laboratory. All populations showed phenotypic plasticity in
      flight initiation distance, suggesting that this feature is ancient and could
      have helped wall lizards survive the initial introduction of cats to the region.
      Lizards from islets sought shelter less frequently and often initially approached
      the cat decoy. These differences reflect changes since islet isolation and could
      render islet lizards strongly susceptible to cat predation. 

PMID- 24943366
TI  - A population of sexual Daphnia pulex resists invasion by asexual clones.
AB  - Asexual reproduction avoids the costs associated with sex, predicting that
      invading asexual clones can quickly replace sexual populations. Daphnia pulex
      populations in the Great Lakes area are predominately asexual, but the
      elimination of sexual populations by invading clones is poorly understood.
      Asexual clones were detected at low frequency in one rare sexual population in
      1995, with some increase in frequency during 2003 and 2004. However, these clones
      remained at low frequency during further yearly sampling (2005-2013) with no
      evidence that the resident sexual population was in danger of elimination. There
      was evidence for hybridization between rare males produced by asexual clones and
      sexual females with the potential to produce new asexual genotypes and spread the
      genetic factors for asexuality. In a short-term laboratory competition
      experiment, the two most common asexual clones did not increase in frequency
      relative to a genetically diverse sexual population due in part to a greater
      investment in diapausing eggs that trades-off current population growth for
      increased contribution to the egg bank. Our results suggest that a successful
      invasion can be prolonged, requiring a combination of clonal genotypes with high
      fitness, persistence of clones in the egg bank and negative factors affecting the
      sexual population such as inbreeding depression resulting from population
      bottlenecks. 

PMID- 24943367
TI  - Predatory fish sounds can alter crab foraging behaviour and influence bivalve
      abundance.
AB  - The risk of predation can have large effects on ecological communities via
      changes in prey behaviour, morphology and reproduction. Although prey can use a
      variety of sensory signals to detect predation risk, relatively little is known
      regarding the effects of predator acoustic cues on prey foraging behaviour. Here
      we show that an ecologically important marine crab species can detect sound
      across a range of frequencies, probably in response to particle acceleration.
      Further, crabs suppress their resource consumption in the presence of
      experimental acoustic stimuli from multiple predatory fish species, and the sign
      and strength of this response is similar to that elicited by water-borne chemical
      cues. When acoustic and chemical cues were combined, consumption differed from
      expectations based on independent cue effects, suggesting redundancies among cue
      types. These results highlight that predator acoustic cues may influence prey
      behaviour across a range of vertebrate and invertebrate taxa, with the potential
      for cascading effects on resource abundance. 

PMID- 24943368
TI  - Consequences of plant invasions on compartmentalization and species' roles in
      plant-pollinator networks.
AB  - Compartmentalization-the organization of ecological interaction networks into
      subsets of species that do not interact with other subsets (true compartments) or
      interact more frequently among themselves than with other species (modules)-has
      been identified as a key property for the functioning, stability and evolution of
      ecological communities. Invasions by entomophilous invasive plants may profoundly
      alter the way interaction networks are compartmentalized. We analysed a
      comprehensive dataset of 40 paired plant-pollinator networks (invaded versus
      uninvaded) to test this hypothesis. We show that invasive plants have higher
      generalization levels with respect to their pollinators than natives. The
      consequences for network topology are that-rather than displacing native species
      from the network-plant invaders attracting pollinators into invaded modules tend
      to play new important topological roles (i.e. network hubs, module hubs and
      connectors) and cause role shifts in native species, creating larger modules that
      are more connected among each other. While the number of true compartments was
      lower in invaded compared with uninvaded networks, the effect of invasion on
      modularity was contingent on the study system. Interestingly, the generalization
      level of the invasive plants partially explains this pattern, with more
      generalized invaders contributing to a lower modularity. Our findings indicate
      that the altered interaction structure of invaded networks makes them more robust
      against simulated random secondary species extinctions, but more vulnerable when
      the typically highly connected invasive plants go extinct first. The consequences
      and pathways by which biological invasions alter the interaction structure of
      plant-pollinator communities highlighted in this study may have important
      dynamical and functional implications, for example, by influencing multi-species
      reciprocal selection regimes and coevolutionary processes. 

PMID- 24943371
TI  - Elaborate visual and acoustic signals evolve independently in a large,
      phenotypically diverse radiation of songbirds.
AB  - The concept of a macroevolutionary trade-off among sexual signals has a storied
      history in evolutionary biology. Theory predicts that if multiple sexual signals
      are costly for males to produce or maintain and females prefer a single, sexually
      selected trait, then an inverse correlation between sexual signal elaborations is
      expected among species. However, empirical evidence for what has been termed the
      'transfer hypothesis' is mixed, which may reflect different selective pressures
      among lineages, evolutionary covariates or methodological differences among
      studies. Here, we examine interspecific correlations between song and plumage
      elaboration in a phenotypically diverse, widespread radiation of songbirds, the
      tanagers. The tanagers (Thraupidae) are the largest family of songbirds,
      representing nearly 10% of all songbirds. We assess variation in song and plumage
      elaboration across 301 species, representing the largest scale comparative study
      of multimodal sexual signalling to date. We consider whether evolutionary
      covariates, including habitat, structural and carotenoid-based coloration, and
      subfamily groupings influence the relationship between song and plumage
      elaboration. We find that song and plumage elaboration are uncorrelated when
      considering all tanagers, although the relationship between song and plumage
      complexity varies among subfamilies. Taken together, we find that elaborate
      visual and vocal sexual signals evolve independently among tanagers. 

PMID- 24943370
TI  - Immune defence strategies of generalist and specialist insect herbivores.
AB  - Ecological immunology examines the adaptive responses of animals to pathogens in
      relation to other environmental factors and explores the consequences of trade
      offs between investment in immune function and other life-history traits. Among
      species of herbivorous insects, diet breadth may vary greatly, with generalists
      consuming a wide variety of plant families and specialists restricted to a few
      species. Generalists may thus be exposed to a wider range of pathogens exerting
      stronger selection on the innate immune system. To examine whether this produces
      an increase in the robustness of the immune response, we compared larvae of the
      generalist herbivore Heliothis virescens and the specialist Heliothis subflexa
      challenged by entomopathogenic and non-pathogenic bacteria. Heliothis virescens
      larvae showed lower mortality, a lower number of recoverable bacteria, lower
      proliferation of haemocytes and higher phagocytic activity. These results
      indicate a higher tolerance to entomopathogenic bacteria by the generalist, which
      is associated with a more efficient cell-mediated immune response by mechanisms
      that differ between these closely related species. Our findings provide novel
      insights into the consequences of diet breadth and related environmental factors,
      which may be significant in further studies to understand the ecological forces
      and investment trade-offs that shape the evolution of innate immunity. 

PMID- 24943372
TI  - Cumulative frequency-dependent selective episodes allow for rapid morph cycles
      and rock-paper-scissors dynamics in species with overlapping generations.
AB  - Rock-paper-scissors (RPS) dynamics, which maintain genetic polymorphisms over
      time through negative frequency-dependent (FD) selection, can evolve in short
      lived species with no generational overlap, where they produce rapid morph
      frequency cycles. However, most species have overlapping generations and thus,
      rapid RPS dynamics are thought to require stronger FD selection, the existence of
      which yet needs to be proved. Here, we experimentally demonstrate that two
      cumulative selective episodes, FD sexual selection reinforced by FD selection on
      offspring survival, generate sufficiently strong selection to generate rapid
      morph frequency cycles in the European common lizard Zootoca vivipara, a multi
      annual species with major generational overlap. These findings show that the
      conditions required for the evolution of RPS games are fulfilled by almost all
      species exhibiting genetic polymorphisms and suggest that RPS games may be
      responsible for the maintenance of genetic diversity in a wide range of species. 

PMID- 24943373
TI  - Pair bonding prevents reinforcing effects of testosterone in male California mice
      in an unfamiliar environment.
AB  - Testosterone (T) can be released by stimuli such as social interactions, and
      thereby influence future social behaviours. Because the reinforcing effects of T
      can induce preferences for specific environmental locations, T has the potential
      to alter behaviour through space use. In a monogamous species, this T pulse may
      contribute differently to space use in sexually naive (SN) and pair-bonded (PB)
      males: SN males may be more likely to explore new areas to set up a territory
      than PB males, which are more likely to defend an existing, established
      territory. In this study, we test for variation in T-driven space use by
      examining variation in the formation of conditioned place preferences (CPPs) in
      SN and PB male California mice. In the three-chambered CPP apparatus,
      subcutaneous administrations of physiological levels of T were used to repeatedly
      condition SN and PB males to a side chamber, which is an unfamiliar/neutral
      environment. The final tests revealed that T-induced CPPs in the side chamber are
      developed in SN, but not PB males. This study fills a gap in our knowledge about
      plasticity in the rewarding nature of T pulses, based on past social experience. 

PMID- 24943369
TI  - Independently recruited oxidases from the glucose-methanol-choline oxidoreductase
      family enabled chemical defences in leaf beetle larvae (subtribe Chrysomelina) to
      evolve.
AB  - Larvae of the leaf beetle subtribe Chrysomelina sensu stricto repel their enemies
      by displaying glandular secretions that contain defensive compounds. These
      repellents can be produced either de novo (iridoids) or by using plant-derived
      precursors (e.g. salicylaldehyde). The autonomous production of iridoids, as in
      Phaedon cochleariae, is the ancestral chrysomeline chemical defence and predates
      the evolution of salicylaldehyde-based defence. Both biosynthesis strategies
      include an oxidative step of an alcohol intermediate. In salicylaldehyde
      producing species, this step is catalysed by salicyl alcohol oxidases (SAOs) of
      the glucose-methanol-choline (GMC) oxidoreductase superfamily, but the enzyme
      oxidizing the iridoid precursor is unknown. Here, we show by in vitro as well as
      in vivo experiments that P. cochleariae also uses an oxidase from the GMC
      superfamily for defensive purposes. However, our phylogenetic analysis of
      chrysomeline GMC oxidoreductases revealed that the oxidase of the iridoid pathway
      originated from a GMC clade different from that of the SAOs. Thus, the evolution
      of a host-independent chemical defence followed by a shift to a host-dependent
      chemical defence in chrysomeline beetles coincided with the utilization of genes
      from different GMC subfamilies. These findings illustrate the importance of the
      GMC multi-gene family for adaptive processes in plant-insect interactions. 

PMID- 24943374
TI  - Experimental antibiotic treatment identifies potential pathogens of white band
      disease in the endangered Caribbean coral Acropora cervicornis.
AB  - Coral diseases have been increasingly reported over the past few decades and are
      a major contributor to coral decline worldwide. The Caribbean, in particular, has
      been noted as a hotspot for coral disease, and the aptly named white syndromes
      have caused the decline of the dominant reef building corals throughout their
      range. White band disease (WBD) has been implicated in the dramatic loss of
      Acropora cervicornis and Acropora palmata since the 1970s, resulting in both
      species being listed as critically endangered on the International Union for
      Conservation of Nature Red list. The causal agent of WBD remains unknown,
      although recent studies based on challenge experiments with filtrate from
      infected hosts concluded that the disease is probably caused by bacteria. Here,
      we report an experiment using four different antibiotic treatments, targeting
      different members of the disease-associated microbial community. Two antibiotics,
      ampicillin and paromomycin, arrested the disease completely, and by comparing
      with community shifts brought about by treatments that did not arrest the
      disease, we have identified the likely candidate causal agent or agents of WBD.
      Our interpretation of the experimental treatments is that one or a combination of
      up to three specific bacterial types, detected consistently in diseased corals
      but not detectable in healthy corals, are likely causal agents of WBD. In
      addition, a histophagous ciliate (Philaster lucinda) identical to that found
      consistently in association with white syndrome in Indo-Pacific acroporas was
      also consistently detected in all WBD samples and absent in healthy coral.
      Treatment with metronidazole reduced it to below detection limits, but did not
      arrest the disease. However, the microscopic disease signs changed, suggesting a
      secondary role in disease causation for this ciliate. In future studies to
      identify a causal agent of WBD via tests of Henle-Koch's postulates, it will be
      vital to experimentally control for populations of the other potential pathogens
      identified in this study. 

PMID- 24943375
TI  - When is it socially acceptable to feel sick?
AB  - Disease is a ubiquitous and powerful evolutionary force. Hosts have evolved
      behavioural and physiological responses to disease that are associated with
      increased survival. Behavioural modifications, known as 'sickness behaviours',
      frequently involve symptoms such as lethargy, somnolence and anorexia. Current
      research has demonstrated that the social environment is a potent modulator of
      these behaviours: when conflicting social opportunities arise, animals can
      decrease or entirely forgo experiencing sickness symptoms. Here, I review how
      different social contexts, such as the presence of mates, caring for offspring,
      competing for territories or maintaining social status, affect the expression of
      sickness behaviours. Exploiting the circumstances that promote this behavioural
      plasticity will provide new insights into the evolutionary ecology of social
      behaviours. A deeper understanding of when and how this modulation takes place
      may lead to better tools to treat symptoms of infection and be relevant for the
      development of more efficient disease control programmes. 

PMID- 24943376
TI  - Flying rocks and flying clocks: disparity in fossil and molecular dates for
      birds.
AB  - Major disparities are recognized between molecular divergence dates and fossil
      ages for critical nodes in the Tree of Life, but broad patterns and underlying
      drivers remain elusive. We harvested 458 molecular age estimates for the stem and
      crown divergences of 67 avian clades to explore empirical patterns between these
      alternate sources of temporal information. These divergence estimates were, on
      average, over twice the age of the oldest fossil in these clades. Mitochondrial
      studies yielded older ages than nuclear studies for the vast majority of clades.
      Unexpectedly, disparity between molecular estimates and the fossil record was
      higher for divergences within major clades (crown divergences) than divergences
      between major clades (stem divergences). Comparisons of dates from studies
      classed by analytical methods revealed few significant differences. Because true
      divergence ages can never be known with certainty, our study does not answer the
      question of whether fossil gaps or molecular dating error account for a greater
      proportion of observed disparity. However, empirical patterns observed here
      suggest systemic overestimates for shallow nodes in existing molecular divergence
      dates for birds. We discuss underlying biases that may drive these patterns. 

PMID- 24943377
TI  - Hydrodynamics of fossil fishes.
AB  - From their earliest origins, fishes have developed a suite of adaptations for
      locomotion in water, which determine performance and ultimately fitness. Even
      without data from behaviour, soft tissue and extant relatives, it is possible to
      infer a wealth of palaeobiological and palaeoecological information. As in extant
      species, aspects of gross morphology such as streamlining, fin position and tail
      type are optimized even in the earliest fishes, indicating similar life
      strategies have been present throughout their evolutionary history. As
      hydrodynamical studies become more sophisticated, increasingly complex fluid
      movement can be modelled, including vortex formation and boundary layer control.
      Drag-reducing riblets ornamenting the scales of fast-moving sharks have been
      subjected to particularly intense research, but this has not been extended to
      extinct forms. Riblets are a convergent adaptation seen in many Palaeozoic
      fishes, and probably served a similar hydrodynamic purpose. Conversely,
      structures which appear to increase skin friction may act as turbulisors,
      reducing overall drag while serving a protective function. Here, we examine the
      diverse adaptions that contribute to drag reduction in modern fishes and review
      the few attempts to elucidate the hydrodynamics of extinct forms. 

PMID- 24943378
TI  - Collision avoidance during group evasive manoeuvres: a comparison of real versus
      simulated swarms with manipulated vision and surface wave detectors.
AB  - Coordinated group motion has been studied extensively both in real systems
      (flocks, swarms and schools) and in simulations (self-propelled particle (SPP)
      models using attraction and repulsion rules). Rarely are attraction and repulsion
      rules manipulated, and the resulting emergent behaviours of real and simulation
      systems are compared. We compare swarms of sensory-deprived whirligig beetles
      with matching simulation models. Whirligigs live at the water's surface and
      coordinate their grouping using their eyes and antennae. We filmed groups of
      beetles in which antennae or eyes had been unilaterally obstructed and measured
      individual and group behaviours. We then developed and compared eight SPP
      simulation models. Eye-less beetles formed larger diameter resting groups than
      antenna-less or control groups. Antenna-less groups collided more often with each
      other during evasive group movements than did eye-less or control groups.
      Simulations of antenna-less individuals produced no difference from a control (or
      a slight decrease) in group diameter. Simulations of eye-less individuals
      produced an increase in group diameter. Our study is important in (i)
      differentiating between group attraction and repulsion rules, (ii) directly
      comparing emergent properties of real and simulated groups, and (iii) exploring a
      new sensory modality (surface wave detection) to coordinate group movement. 

PMID- 24943380
TI  - Evaluation of bio-rad geenius HIV-1 and -2 assay as a confirmatory assay for
      detection of HIV-1 and -2 antibodies.
AB  - The performance of the new Bio-Rad Geenius HIV-1/2 confirmatory assay was
      compared with that of the Chiron RIBA HIV-1/HIV-2 strip immunoblot assay using
      166 samples from HIV-1-, HIV-2-, or HIV-1/2-positive and HIV-negative individuals
      and two quality control panels. Our results indicate that the Geenius assay is a
      suitable alternative for confirmatory HIV testing. 

PMID- 24943379
TI  - Cuspal deflection and cervical microleakage scores to determine the adhesive
      potential of universal bonding systems.
AB  - OBJECTIVES: To assess the adhesive performance of three universal bonding systems
      (self-etch and total-etch protocols) with cuspal deflection and cervical
      microleakage score. METHODS: Fifty-six standardised sound maxillary premolar
      teeth with uniform mesio-occlusal-distal (MOD) cavities were randomly allocated
      to six groups. Restoration with resin-based composite (RBC) was performed in
      conjunction with a universal bonding system facilitated by a quartz-tungsten
      halogen light-curing-unit. The dependent variable was the universal bonding
      protocol (self-etch or total-etch). Buccal and palatal cuspal deflections were
      recorded at 0, 30, 60 and 180s post-irradiation using a twin channel deflection
      measuring gauge. Following restoration, the teeth subjected to 500 thermocycles,
      immersed in a 0.2% basic fuchsin dye for 24h, sectioned and examined for cervical
      microleakage. RESULTS: Comparing between bonding protocol (self-etch or total
      etch), a decrease in total cuspal deflection and a concomitant increase in
      cervical microleakage were evident when employing the total-etch compared with
      the self-etch protocol for two of the three universal dental adhesives.
      CONCLUSIONS: The 'Adhesion-Decalcification concept' suggests a trend towards
      'mild self-etch' adhesives. Differences in adhesive performance (cuspal
      deflection and cervical microleakage) between the teeth restored using the self
      etch or total-etch protocols is suggested to be a result of the pH of the self
      etch solutions. 'Mild self-etch' (pH~2.0) adhesives out-performed ultra-mild
      (pH>2.5) or strong (pH<1.5) self-etch solutions. CLINICAL SIGNIFICANCE: Poorly
      performing adhesives could be identified using the cuspal deflection and cervical
      microleakage protocol reported which could save the complications encountered
      clinically with Class II RBC restorations.

PMID- 24943381
TI  - Matched longitudinal analysis of biomarkers associated with survival.
AB  - The identification of host or pathogen factors linked to clinical outcome is a
      common goal in many animal studies of infectious diseases. When the disease is
      fatal, statistical analysis of such factors may be biased from missing
      observations due to deaths. For example, when observations of a subject are
      censored before completing the intended study period, the complete trajectory
      will not be observed. Even if the factor is not associated with outcome,
      comparisons of data from survivors with those from nonsurvivors may lead to the
      wrong conclusions regarding associations with survival. Comparisons between
      subjects must account for differing observation lengths for those who survive
      relative to those who do not. Analyzing data over an interval common to all
      subjects provides one solution but requires eliminating data, some of which may
      be informative about the differences between groups. Here, we present a novel
      approach, matched longitudinal analysis (MLA), for analyzing such data based on
      matching biomarker intervals for survivors and nonsurvivors. We describe the
      results from simulation studies and from a study of monkeypox virus infection in
      nonhuman primates. In our application, MLA identified low monocyte
      chemoattractant protein-1 (MCP-1) levels as having a statistically significant
      association with survival, whereas the alternative methods did not identify an
      association. The method has general application to longitudinal studies that seek
      to find associations of biomarker changes with survival. 

PMID- 24943382
TI  - Hexon hypervariable region-modified adenovirus type 5 (Ad5) vectors display
      reduced hepatotoxicity but induce T lymphocyte phenotypes similar to Ad5 vectors.
AB  - Hexon modification of adenovirus type 5 (Ad5) vectors with the hypervariable
      regions (HVRs) of Ad48 has been shown to allow Ad5HVR48 vectors to circumvent the
      majority of the preexisting Ad5-neutralizing antibodies. However, it remains
      unclear whether modifying hexon HVRs impacts innate or adaptive immune responses
      elicited by this vector. In this study, we investigated the influence of the HVR
      substitution of Ad5 on innate and adaptive immune responses following
      vaccination. Ad5HVR48 displayed an intermediate level of innate immune cytokines
      and chemokines relative to those of Ad5 and Ad48, consistent with its chimeric
      nature. Hepatotoxicity was observed after Ad5 immunization but not after Ad5HVR48
      or Ad48 immunization. However, the CD8(+) T-cell responses elicited by Ad5HVR48
      vectors displayed a partially exhausted phenotype, as evidenced by the sustained
      expression of programmed death 1 (PD-1), decreased effector-to-central memory
      conversion, and reduced memory recall responses, similar to those elicited by Ad5
      vectors and in contrast to those induced by Ad48 vectors. Taken together, these
      results indicate that although Ad5HVR48 largely bypasses preexisting Ad5
      neutralizing antibodies and shows reduced hepatotoxicity compared to that of Ad5,
      it induces adaptive immune phenotypes that are functionally exhausted similar to
      those elicited by Ad5. 

PMID- 24943384
TI  - Treatment and outcomes of invasive fusariosis: review of 65 cases from the PATH
      Alliance((r)) registry.
AB  - Invasive Fusarium infections occur in immunosuppressed patients, especially those
      with haematological malignancies. We conducted a descriptive analysis of data
      from patients with invasive fusariosis identified in the Prospective Antifungal
      Therapy Alliance registry, which collected data on invasive fungal infections in
      the United States and Canada from 2004 to 2008. In this series of 65 patients
      with proven (83.1%) and probable (16.9%) invasive fusariosis, the most common
      underlying condition was haematological malignancy, in which neutropenia and
      corticosteroid usage frequently occurred. Seven patients with invasive Fusarium
      infections had cross-reactive galactomannan assay results. The survival rate for
      all patients at 90 days was 44%, which was an improvement compared with
      historical data. Disseminated disease occurred frequently (35.4%), and patients
      with and without disseminated disease had survival rates of 33% and 50%,
      respectively. Posaconazole and voriconazole were the most frequently employed
      therapies and may be linked to the improved survival rate observed in this
      patient series. In summary, patients with invasive Fusarium infections continue
      to have high fatality rates, especially those with disseminated disease. Fusarium
      infections should be strongly considered in the absence of Aspergillus isolation
      in patients at high risk of mould infections with positive galactomannan assay
      test results.

PMID- 24943385
TI  - Selecting the best design for nonstandard toxicology experiments.
AB  - Although many experiments in environmental toxicology use standard statistical
      experimental designs, there are situations that arise where no such standard
      design is natural or applicable because of logistical constraints. For example,
      the layout of a laboratory may suggest that each shelf serve as a block, with the
      number of experimental units per shelf either greater than or less than the
      number of treatments in a way that precludes the use of a typical block design.
      In such cases, an effective and powerful alternative is to employ optimal
      experimental design principles, a strategy that produces designs with precise
      statistical estimates. Here, a D-optimal design was generated for an experiment
      in environmental toxicology that has 2 factors, 16 treatments, and constraints
      similar to those described above. After initial consideration of a randomized
      complete block design and an intuitive cyclic design, it was decided to compare a
      D-optimal design and a slightly more complicated version of the cyclic design.
      Simulations were conducted generating random responses under a variety of
      scenarios that reflect conditions motivated by a similar toxicology study, and
      the designs were evaluated via D-efficiency as well as by a power analysis. The
      cyclic design performed well compared to the D-optimal design.

PMID- 24943383
TI  - An H7N1 influenza virus vaccine induces broadly reactive antibody responses
      against H7N9 in humans.
AB  - Emerging H7N9 influenza virus infections in Asia have once more spurred the
      development of effective prepandemic H7 vaccines. However, many vaccines based on
      avian influenza viruses--including H7--are poorly immunogenic, as measured by
      traditional correlates of protection. Here we reevaluated sera from an H7N1 human
      vaccine trial performed in 2006. We examined cross-reactive antibody responses to
      divergent H7 strains, including H7N9, dissected the antibody response into head-
      and stalk-reactive antibodies, and tested the in vivo potency of these human sera
      in a passive-transfer H7N9 challenge experiment with mice. Although only a low
      percentage of vaccinees induced neutralizing antibody responses against the
      homologous vaccine strain and also H7N9, we detected strong cross-reactivity to
      divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a
      quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination
      induced antibodies to both the head and stalk domains of the HA, which is in
      sharp contrast to seasonal inactivated vaccines. Finally, we were able to show
      that both neutralizing and nonneutralizing antibodies improved in vivo virus
      clearance in a passive-transfer H7N9 challenge mouse model.

PMID- 24943386
TI  - Herpes simplex gastritis causing pyloric stenosis.

PMID- 24943387
TI  - Outcome of mood stabilizer discontinuation in bipolar disorder after 5 years of
      euthymia.
AB  - OBJECTIVE: The objective was to study the outcome of mood stabilizer
      discontinuation on recurrence in patients with bipolar disorder after at least 5
      years of euthymia. METHODS: Twenty-three patients diagnosed with bipolar
      affective disorder according to the International Classification of Diseases,
      10th Revision Diagnostic Criteria for Research, receiving mood stabilizer
      prophylaxis for at least 5 years, had undergone planned discontinuation, and the
      rates and time to recurrence were studied. RESULTS: Twenty (87%) of 23 patients
      had recurrence, and all of the episodes were manic. Kaplan-Meier survival
      analysis showed median time to recurrence following discontinuation of mood
      stabilizer prophylaxis was 10 months (SE, 6.06 months; 95% confidence interval, 0
      to 21.89 months). CONCLUSION: Four fifths of our patients had recurrence
      following discontinuation of mood stabilizer prophylaxis within 10 months.

PMID- 24943388
TI  - Effects of low-dose olanzapine on duloxetine-related nausea and vomiting for the
      treatment of major depressive disorder.
AB  - OBJECTIVE: This study aims to investigate the effects of low-dose olanzapine on
      preventing occurrence and controlling the severity of nausea and vomiting related
      to duloxetine in treating major depressive disorder. METHODS: Two hundred sixty
      eight subjects with major depressive disorder were divided into control and trial
      groups. The control group had 165 subjects and was treated with duloxetine only,
      whereas the trial group had 103 subjects and received duloxetine combined with
      low-dose olanzapine. After the treatment for 2 weeks, both groups were evaluated
      for occurrence and severity of adverse effects on digestive tract using the
      Treatment Emergent Symptom Scale. RESULTS: The trial group, scored at 13, showed
      significantly less occurrence and severity of nausea and vomiting than the
      control group, scored at 38 (P < 0.05). The occurrence of nausea and vomiting in
      the trial group is significantly lower compared with that in the control group,
      and the occurrence decreases as the dose of olanzapine increases (P < 0.05). The
      antiemetic effect of olanzapine is valid to all subjects who received it.
      CONCLUSIONS: Duloxetine combined with low-dose olanzapine can effectively reduce
      the occurrence and severity of duloxetine-related nausea and vomiting. With the
      increase of olanzapine dose, the antiemetic effect becomes stronger. Olanzapine
      is a safe and efficient drug for the prevention of duloxetine-related nausea and
      vomiting.

PMID- 24943390
TI  - Prescription patterns of psychotropic medications for the treatment of psychotic
      disorders in the largest mental health institutions of Uganda.
AB  - The study describes prescription patterns of psychotropic medications for
      patients treated for psychosis in psychiatric hospitals of Uganda. A cross
      sectional quantitative survey of age, sex, diagnoses, and psychotropic medication
      of 682 psychiatric inpatients of the 2 national referral hospitals in Uganda was
      conducted on 1 day in March 2012. The percentage of patients treated with the
      same substance within the diagnostic categories schizophrenia, bipolar affective
      disorder, unspecified psychosis, and depressive disorder was calculated. Close to
      90% of the patients with conditions diagnosed with any psychotic disorder were
      treated with first-generation antipsychotic drugs (eg, chlorpromazine,
      haloperidol, trifluoperazine, and depot fluphenazine). Carbamazepine in
      combination with first-generation antipsychotics was prescribed frequently (45%)
      for the treatment of bipolar affective disorder. The use of second-generation
      antipsychotics, lithium, and valproic acid was exceptional. Patients with
      depression usually received a combination (63%) of first-generation
      antipsychotics and antidepressants (fluoxetine or amitriptyline). Benzodiazepines
      were only infrequently used for patients diagnosed with psychoses. First
      generation antipsychotics, antidepressants, and carbamazepine were the most
      frequently used medications for treatment of psychosis in Uganda. Although
      lithium and valproic acid were on the essential drug list in Uganda, their use
      was still infrequent. There is a need to ensure the practical availability of the
      drugs listed on the essential drug list and to support the implementation of
      their use in clinical practice. 

PMID- 24943389
TI  - A naturalistic comparison of the long-term metabolic adverse effects of clozapine
      versus other antipsychotics for patients with psychotic illnesses.
AB  - OBJECTIVE: Clozapine, an evidence-based treatment of refractory schizophrenia, is
      associated with increased weight gain and metabolic dysregulation compared with
      most antipsychotics in short-term clinical trials. However, there are limited
      data describing comparative long-term metabolic risks. In this report, we
      examined whether short-term differences persist with long-term exposure to
      clozapine. METHODS: The data of all patients in a university-based clinic with a
      psychotic illness or a mood disorder with psychotic features, based on the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision diagnosis, and treated with an antipsychotic in calendar year 2012 were
      examined. A total of 307 patients met the criteria; 96 patients were treated with
      clozapine and the remaining 211 patients were treated with 1 or more non
      clozapine antipsychotics. Body mass index, type 2 diabetes, hypertension,
      dyslipidemia, and obesity were compared. RESULTS: The mean duration of the
      clozapine treatment was 7.6 years (range, 2 months to 21 y). On all metabolic
      measures, there were no statistically significant differences between the
      clozapine and non-clozapine groups (mean body mass index, 31 vs 32; type 2
      diabetes, 17% vs 18%; dyslipidemia, 35% vs 38%; hypertension, 32% vs 39%; and
      obesity, 48% vs 54%). Removing the olanzapine-treated patients (n = 51) from the
      non-clozapine group did not change the findings. CONCLUSIONS: In this university
      based clinic sample with a large number of clozapine-treated patients, we found
      no evidence of increased risk in any individual measure for those receiving
      clozapine. Although speculative, the relative contribution of the increased short
      term metabolic risk associated with clozapine may be diminished over time because
      multiple other variables likely also impact metabolic risk during the life span.
      Although speculative, the relative contribution of the increased short-term
      metabolic risk associated with clozapine may be diminished over time due to the
      accumulated impact of other variables that also impact metabolic risk across the
      life span.

PMID- 24943391
TI  - Escitalopram efficacy in depression: a cross-ethnicity examination of the
      serotonin transporter promoter polymorphism.
AB  - Current evidence suggests that polymorphism in the serotonin transporter gene (5
      HTTLPR) predicts antidepressant efficacy in whites but less so in Asians.
      However, it is not clear whether this effect can be observed for specific types
      of antidepressant drugs. White (n = 47) and Korean (n = 118) participants with
      major depressive disorder were treated with escitalopram and assessed over 8
      weeks. Among those with the l/l but not l/s or s/s genotypes, whites had greater
      depression score reductions, response rates, and remission rates compared with
      Koreans. Our results suggest that 5-HTTLPR predicts escitalopram efficacy in an
      ethnicity-dependent manner. 

PMID- 24943392
TI  - Influence of vitamin D consumption and levels on the development of psychiatric
      disorders.

PMID- 24943393
TI  - Compulsive behaviors related to rasagiline: a case report.

PMID- 24943394
TI  - Lamotrigine reduces affective instability in depressed patients with mixed mood
      and anxiety disorders.

PMID- 24943395
TI  - Quetiapine in postpartum psychosis.

PMID- 24943397
TI  - Howard Williams oration: preventing the unpreventable: the 'cot death' story.

PMID- 24943396
TI  - Striatal adenosine A2A receptor expression is controlled by S-adenosyl-L
      methionine-mediated methylation.
AB  - Adenosine A2A receptor (A2AR) is a G protein-coupled receptor enriched in the
      striatum for which an increased expression has been demonstrated in certain
      neurological diseases. Interestingly, previous in vitro studies demonstrated that
      A2AR expression levels are reduced after treatment with S-adenosyl-L-methionine
      (SAM), a methyl donor molecule involved in the methylation of important
      biological structures such as DNA, proteins, and lipids. However, the in vivo
      effects of SAM treatment on A2AR expression are still obscure. Here, we
      demonstrated that 2 weeks of SAM treatment produced a significant reduction in
      the rat striatal A2AR messenger RNA (mRNA) and protein content as well as A2AR
      mediated signaling. Furthermore, when the content of 5-methylcytosine levels in
      the 5'UTR region of ADORA2A was analyzed, this was significantly increased in the
      striatum of SAM-treated animals; thus, an unambiguous correlation between SAM
      mediated methylation and striatal A2AR expression could be established. Overall,
      we concluded that striatal A2AR functionality can be controlled by SAM treatment,
      an issue that might be relevant for the management of these neurological
      conditions that course with increased A2AR expression. 

PMID- 24943399
TI  - Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is
      associated with reduced optineurin expression in a subset of patients.
AB  - Crohn's disease (CD) is a complex and highly heterogeneous chronic inflammatory
      disorder, primarily affecting the gastrointestinal tract. Genetic and functional
      studies have highlighted a key role for innate immunity in its pathogenesis.
      Profound systemic defects in innate immunity and acute inflammation are
      understood to result in markedly delayed clearance of bacteria from the tissues,
      leading to local chronic granulomatous inflammation and compensatory adaptive
      immunological changes. Macrophages, key orchestrators of acute inflammation, are
      likely to play an important role in the initial impaired innate immune response.
      Monocyte-derived macrophages from CD patients stimulated with Escherichia coli
      were shown to release attenuated levels of tumour necrosis factor and interferon
      gamma with normal secretion of interleukin-8 (IL-8), IL-10 and IL-6. In controls,
      the secretion of these cytokines was strongly positively correlated, which was
      not seen with CD macrophages. The transcriptomes of CD and control macrophages
      were examined in an attempt to understand the molecular basis of this defect.
      There were no differentially expressed genes identified between the two groups,
      consistent with genetic heterogeneity; however, a number of molecules were found
      to be under-expressed in subgroups of CD patients. The most common of these was
      optineurin (OPTN) which was under-expressed in approximately 10% of the CD
      patients. Reduced OPTN expression coincided with lower intracellular protein
      levels and diminished cytokine secretion after bacterial stimulation both in the
      patients and with small interfering RNA knockdown in THP-1 cells. Identifying and
      studying subgroups of patients with shared defective gene expression could aid
      our understanding of the mechanisms underlying highly heterogeneous diseases such
      as CD. 

PMID- 24943400
TI  - Simultaneous determination of glucose, triglycerides, urea, cholesterol, albumin
      and total protein in human plasma by Fourier transform infrared spectroscopy:
      direct clinical biochemistry without reagents.
AB  - OBJECTIVE: Direct measurement of chemical constituents in complex biologic
      matrices without the use of analyte specific reagents could be a step forward
      toward the simplification of clinical biochemistry. Problems related to reagents
      such as production errors, improper handling, and lot-to-lot variations would be
      eliminated as well as errors occurring during assay execution. We describe and
      validate a reagent free method for direct measurement of six analytes in human
      plasma based on Fourier-transform infrared spectroscopy (FTIR). DESIGN AND
      METHODS: Blood plasma is analyzed without any sample preparation. FTIR spectrum
      of the raw plasma is recorded in a sampling cuvette specially designed for
      measurement of aqueous solutions. For each analyte, a mathematical calibration
      process is performed by a stepwise selection of wavelengths giving the optimal
      least-squares correlation between the measured FTIR signal and the analyte
      concentration measured by conventional clinical reference methods. The developed
      calibration algorithms are subsequently evaluated for their capability to predict
      the concentration of the six analytes in blinded patient samples. RESULTS: The
      correlation between the six FTIR methods and corresponding reference methods were
      0.87<R(2)<1.00. The interassay imprecision meets international quality criteria
      for all the six analytes. The linearity of the FTIR methods extends over the
      clinically significant concentration ranges. Visible hemolysis and icterus have
      some influence on the measurements. Plasma samples can be stored at 2-8 degrees C
      for at least 8 days before the analysis. CONCLUSIONS: The developed FTIR methods
      use a simple and robust technology to achieve stable and accurate results that
      meet international quality criteria for the measurement of glucose,
      triglycerides, urea, cholesterol, albumin and total protein in human plasma.

PMID- 24943398
TI  - Fine-scale population epigenetic structure in relation to gastrointestinal
      parasite load in red grouse (Lagopus lagopus scotica).
AB  - Epigenetic modification of cytosine methylation states can be elicited by
      environmental stresses and may be a key process affecting phenotypic plasticity
      and adaptation. Parasites are potent stressors with profound physiological and
      ecological effects on their host, but there is little understanding in how
      parasites may influence host methylation states. Here, we estimate epigenetic
      diversity and differentiation among 21 populations of red grouse (Lagopus lagopus
      scotica) in north-east Scotland and test for association of gastrointestinal
      parasite load (caecal nematode Trichostrongylus tenuis) with hepatic genome-wide
      and locus-specific methylation states. Following methylation-sensitive AFLP
      (MSAP), 129 bands, representing 73 methylation-susceptible and 56 nonmethylated
      epiloci, were scored across 234 individuals. The populations differed
      significantly in genome-wide methylation levels and were also significantly
      epigenetically (F(SC) = 0.0227; P < 0.001) and genetically (F(SC) = 0.0058; P <
      0.001) differentiated. Parasite load was not associated with either genome-wide
      methylation levels or epigenetic differentiation. Instead, we found eight
      disproportionately differentiated epilocus-specific methylation states (F(ST)
      outliers) using bayescan software and significant positive and negative
      association of 35 methylation states with parasite load from bespoke generalized
      estimating equations (GEE), simple logistic regression (sam) and Bayesian
      environmental analysis (bayenv2). Following Sanger sequencing, genome mapping and
      geneontology (go) annotation, some of these epiloci were linked to genes involved
      in regulation of cell cycle, signalling, metabolism, immune system and notably
      rRNA methylation, histone acetylation and small RNAs. These findings demonstrate
      an epigenetic signature of parasite load in populations of a wild bird and
      suggest intriguing physiological effects of parasite-associated cytosine
      methylation.

PMID- 24943401
TI  - A simple computer program to quantify red desaturation in patients with optic
      neuritis.
AB  - PURPOSE: Red desaturation is a subjective, sensitive test for patients with optic
      nerve disease. There is no quantitative clinical test to measure the severity of
      color desaturation. The current study introduces a simple PowerPoint presentation
      for quantification of red desaturation in patients with optic neuritis. METHODS:
      A Microsoft Office PowerPoint presentation was designed. A red square is shown on
      each half of the screen. The degree of desaturation on one side is increased in
      each successive slide. The patient holds a black cardboard divider between
      his/her eyes, such that each eye can see one-half of the screen. The patient uses
      the mouse to forward through the slides, thereby gradually increasing the
      desaturation of the red square presented to the normal eye until it matches the
      color of the red square seen with the tested eye. Desaturation is graded by the
      number of slide changes needed until subjective equal color between the eyes is
      perceived. The test was presented to normal volunteers and to patients with optic
      neuritis. The difference in saturation levels between the right and the left eyes
      in patients with optic neuritis vs controls was compared. RESULTS: A total of 83
      patients were included. Patients with optic neuritis had significantly increased
      desaturation compared to controls (6.17 +/- 3.3 vs 0.24 +/- 2.8 respectively; p <
      0.0001). CONCLUSIONS: This test is easy to create and efficiently quantifies the
      severity of red desaturation.

PMID- 24943403
TI  - The effect of pi-conjugation in the macrocyclic ring on the photophysical
      properties of a series of thiaaceneporphyrinoids.
AB  - In a series of thiaaceneporphyrinoids, their conformers exhibit macrocyclic pi
      conjugation pathways controlled by a dihedral angle between the porphyrin
      framework and acene planes. Conformational equilibria significantly affect the
      photophysical properties of these macrocycles. 

PMID- 24943404
TI  - Why is intelligence associated with stability of happiness?
AB  - In the National Child Development Study, life-course variability in happiness
      over 18 years was significantly negatively associated with its mean level
      (happier individuals were more stable in their happiness, and it was not due to
      the ceiling effect), as well as childhood general intelligence and all Big Five
      personality factors (except for Agreeableness). In a multiple regression
      analysis, childhood general intelligence was the strongest predictor of life
      course variability in life satisfaction, stronger than all Big Five personality
      factors, including Emotional stability. More intelligent individuals were
      significantly more stable in their happiness, and it was not entirely because:
      (1) they were more educated and wealthier (even though they were); (2) they were
      healthier (even though they were); (3) they were more stable in their marital
      status (even though they were); (4) they were happier (even though they were);
      (5) they were better able to assess their own happiness accurately (even though
      they were); or (6) they were better able to recall their previous responses more
      accurately or they were more honest in their survey responses (even though they
      were both). While I could exclude all of these alternative explanations, it
      ultimately remained unclear why more intelligent individuals were more stable in
      their happiness.

PMID- 24943405
TI  - Iatrogenic anemia (can it be prevented?).
AB  - 'Iatrogenic anemia' is a condition of lowered hematocrit and hemoglobin count
      resulting from large or frequent removal of blood samples, usually for laboratory
      testing. It is frequently seen in patients who are already suffering from bone
      marrow depression, and thus may become a comorbidity. Because several different
      types of chemical agents may be required for test procedures, a large volume of
      blood could be removed for each set of testing, perhaps 50-60 mL. Often local and
      reference laboratories request larger samples than are really necessary to
      perform a given test and still have some left to perform any required repeat
      testing. My experience shows that a volume of about 3 mL of each type of sample
      should be sufficient for this purpose. 

PMID- 24943402
TI  - Protease-sensitive PEG hydrogels regulate vascularization in vitro and in vivo.
AB  - Forming functional blood vessel networks in engineered or ischemic tissues is a
      significant scientific and clinical hurdle. Poly(ethylene glycol) (PEG)-based
      hydrogels are adapted to investigate the role of mechanical properties and
      proteolytic susceptibility on vascularization. Four arm PEG vinyl sulfone is
      polymerized by Michael-type addition with cysteine groups on a slowly degraded
      matrix metalloprotease (MMP) susceptible peptide, GPQG?IWGQ, or a more rapidly
      cleaved peptide, VPMS?MRGG. Co-encapsulation of endothelial cells and supportive
      fibroblasts within the gels lead to vascular morphogenesis in vitro that is
      robust to changes in crosslinking peptide identity, but is significantly
      attenuated by increased crosslinking and MMP inhibition. Perfused vasculature
      forms from transplanted cells in vivo in all gel types; however, in contrast to
      the in vitro results, vascularization in vivo is not decreased in the more
      crosslinked gels. Collectively, these findings demonstrate the utility of this
      platform to support vascularization both in vitro and in vivo. 

PMID- 24943407
TI  - Blind source identification from the multichannel surface electromyogram.
AB  - The spinal circuitries combine the information flow from the supraspinal centers
      with the afferent input to generate the neural codes that drive the human
      skeletal muscles. The muscles transform the neural drive they receive from alpha
      motor neurons into motor unit action potentials (electrical activity) and force.
      Thus, the output of the spinal cord circuitries can be examined noninvasively by
      measuring the electrical activity of skeletal muscles at the surface of the skin
      i.e. the surface electromyogram (EMG). The recorded multi-muscle EMG activity
      pattern is generated by mixing processes of neural sources that need to be
      identified from the recorded signals themselves, with minimal or no a priori
      information available. Recently, multichannel source separation techniques that
      rely minimally on a priori knowledge of the mixing process have been developed
      and successfully applied to surface EMG. They act at different scales of
      information extraction to identify: (a) the activation signals shared by
      synergistic skeletal muscles, (b) the specific neural activation of individual
      muscles, separating it from that of nearby muscles i.e. from crosstalk, and (c)
      the spike trains of the active motor neurons. This review discusses the
      assumptions made by these methods, the challenges and limitations, as well as
      examples of their current applications. 

PMID- 24943406
TI  - Emergence of resistant variants detected by ultra-deep sequencing after
      asunaprevir and daclatasvir combination therapy in patients infected with
      hepatitis C virus genotype 1.
AB  - Daclatasvir (DCV) and asunaprevir (ASV) are NS5A and NS3 protease-targeted
      antivirals respectively, currently under development for the treatment of chronic
      hepatitis C virus (HCV) infection. We analysed the relationship between pre
      existing drug-resistant variants and clinical outcome of the combination
      treatment with DCV and ASV. Ten patients with HCV genotype 1b were orally treated
      with a combination of ASV and DCV for 24 weeks. The frequencies of amino acid
      (aa) variants at NS3 aa positions 155, 156 and 168 and at NS5A aa31 and 93 before
      and after treatment were analysed by ultra-deep sequencing. We established a
      minimum variant frequency threshold of 0.3% based on plasmid sequencing.
      Sustained virological response (SVR) was achieved in 8 out of 10 patients (80%),
      and relapse of HCV RNA after cessation of the treatment and viral breakthrough
      occurred in the other two patients. Pre-existing DCV-resistant variants (L31V/M
      and/or Y93H; 0.9-99.4%) were detected in three out of eight patients who achieved
      SVR. Pre-existing DCV-resistant variants were detected in a relapsed patient
      (L31M, Y93H) and in a patient with viral breakthrough (Y93H); however, no ASV
      resistant variants were detected. In these patients, HCV RNA rebounded with ASV-
      and DCV- double resistant variants (NS3 D168A/V plus NS5A L31M and Y93H). While
      pre-existing DCV-resistant variants might contribute to viral breakthrough in DCV
      and ASV combination therapy, the effectiveness of prediction of the outcome of
      therapy based on ultra-deep sequence analysis of pre-existing resistant variants
      appears limited.

PMID- 24943408
TI  - The impact of different nasal packings on postoperative complications.
AB  - OBJECTIVE: The objective of this study was to find out if there is any
      association between the use of nasal packings and nasal synechia formation,
      septal perforation, postoperative infection and epistaxis in patients who
      underwent septoplasty and concha reduction operations. METHODS: This
      retrospective study was conducted at a tertiary referral center. One hundred
      thirty patients were randomly selected among patients who underwent endonasal
      surgery in Namik Kemal University Hospital between January 1st 2012 and August
      1st 2013. Retrospective analysis of these patients' files, including operative
      reports and follow-up notes, was done. The postoperative findings of patients who
      had septal splints and Merocel nasal packings were compared and analyzed for
      statistical significance. RESULTS: The results of the study showed a
      statistically significant difference in the frequency of synechia formation
      between two groups (p<0.05). The frequency of synechia formation was found to be
      higher in the Merocel packing group. However, no statistically significant
      difference was found between groups in terms of postoperative infection, septal
      perforation, and epistaxis (p>0.05). CONCLUSION: Our findings suggest that
      intranasal splints are superior to Merocel nasal packings in terms of preventing
      nasal synechia formation. Insertion of a septal splint after nasal surgery should
      be preferred to avoid this complication. On the other hand, other factors should
      be sought in the etiology of postoperative infection, septal perforation, and
      epistaxis.

PMID- 24943409
TI  - Central fat accumulation associated with metabolic risks beyond total fat in
      normal BMI Chinese adults.
AB  - OBJECTIVE: To investigate the association of central fat with metabolic risks in
      normal BMI Chinese people. METHODS: Normal BMI subjects (18.5 <= BMI < 24, n =
      520) aged 18-82 years were included. Blood pressure, triglycerides, high-density
      lipoprotein cholesterol and fasting plasma glucose were collected as metabolic
      risk factors. Dual-energy X-ray absorptiometry was used to measure total and
      central fat. Central fat was indicated as percent trunk fat (%TF) and
      android/gynoid fat ratio. Multiple adjusted regression models were applied to
      investigate the association of total and central fat with metabolic risk factors.
      The assessment values of these fat measures were further compared by receiver
      operating characteristic (ROC) curves. RESULTS: Both total and central fat were
      correlated with metabolic risk factors. After adjusting for BMI, the significant
      association of percent body fat (%BF) with metabolic risks diminished, whereas
      %TF and android/gynoid fat ratio were still correlated. When BMI was replaced
      with %BF in the models, the results remained unchanged. ROC analysis showed the
      areas under the curve (AUCs) of total and central fat for at least two metabolic
      risk factors were comparable in men. However, in women, the AUCs of %TF and
      android/gynoid fat ratio were significantly greater than those of BMI, %BF and
      waist circumference. CONCLUSIONS: Central fat accumulation had a stronger
      association with metabolic risks than total fat in normal BMI Chinese adults,
      particularly in women. Central fat had more important implications in assessing
      'metabolically obese' individuals among normal BMI subjects.

PMID- 24943410
TI  - Are antibiotics beneficial to children suffering from enterovirus infection
      complicated with a high C-reactive protein level?
AB  - BACKGROUND: Enteroviruses are seasonally prevalent each year in Southeast Asia.
      Elevated C-reactive protein (CRP) levels have been noted in minor populations of
      patients, and antibiotics may be prescribed under the impression of a suspected
      bacterial infection. This prescription might be inappropriate, resulting in
      further bacterial resistance and medical expense. The aim of this study was to
      delineate how effective antibiotics are for children suffering from enterovirus
      infection complicated with a high CRP level. METHODS: The medical records of
      children hospitalized between January 2008 and December 2012 with herpangina or
      hand, foot and mouth disease were reviewed retrospectively. The children enrolled
      were divided into three groups, A, B, and C, by CRP level, which were <40, 40-80,
      and >= 80 mg/l, respectively. A case-control study of group C divided into
      subgroups according to the prescription of antibiotics for at least 24h during
      the admission was conducted for further analysis. RESULTS: A total 3566 cases
      were identified; 214 were in group C and 71.0% of them received a prescription
      for antibiotics. There was a linear trend between a relatively higher CRP level
      and a higher proportion of antibiotics prescribed in the three groups (p=0.001).
      In the case-control study, there were no significant differences in age, sex,
      mean CRP, or febrile days. However, a relatively longer stay of hospitalization
      was recorded in the subgroup with an antibiotic prescription (p=0.020).
      CONCLUSIONS: The present study indicated that antibiotics might not be beneficial
      in treating these patients, even those with a high CRP level. Clinicians should
      be more prudent in antibiotic use when no obvious evidence of bacterial infection
      is found.

PMID- 24943411
TI  - Pygmy chameleons of the Rhampholeon platyceps compex (Squamata: Chamaeleonidae):
      description of four new species from isolated 'sky islands' of northern
      Mozambique.
AB  - The taxonomic status of recently discovered populations of pygmy chameleons
      (Rhampholeon) from the northern Mozambique montane isolates of Mt. Chiperone, Mt.
      Mabu, Mt. Inago and Mt. Namuli are assessed, and compared with the closest
      geographical congeners, including Rhampholeon platyceps Gunther 1893 from Mt.
      Mulanje, and Rh. chapmanorum Tilbury 1992 from the Malawi Hills, both in southern
      Malawi. Relationships were examined using morphological features and a
      phylogenetic analysis incorporating two mitochondrial and one nuclear marker. The
      phylogeny showed that each montane isolate contained a distinct, well-supported
      clade of chameleons. Chameleons from the Mozambican montane isolates are within a
      monophyletic clade inclusive of species from southern Malawi (Rh. platyceps and
      Rh. chapmanorum). Although some relationships are unresolved, the southern Malawi
      and Mozambican isolates appear to share their most recent common ancestor with
      species from the Eastern Arc Mountains and Southern Highlands of Tanzania and
      Malawi (Rh. moyeri, Rh. uluguruesis, Rh. nchisiensis). Along with Rh. beraduccii
      and Rh. acuminatus, all are included in the subgenus Rhinodigitum. Sister to this
      larger clade are species from west/central Africa (Rh. temporalis, Rh. spectrum)
      and the Rh. marshalli-gorongosae complex from southwest Mozambique and adjacent
      Zimbabwe. Morphological and molecular results confirm that Brookesia platyceps
      carri Loveridge 1953 is a junior subjective synonym of Rhampholeon platyceps
      Gunther 1892. Historical records of Rh. platyceps from the Shire Highlands
      (Chiromo) and the Zomba Plateau, are incorrect and the species is now considered
      endemic to the Mulanje massif. All of the four newly discovered, isolated
      populations are genetically and morphologically distinct, and we take the
      opportunity to describe each as a new species. Rhampholeon (Rhinodigitum)
      maspictus sp. nov. is restricted to Mt. Mabu and distinguished by its large size,
      well-developed dorsal crenulations, and bright male breeding coloration;
      Rhampholeon (Rhinodigitum) nebulauctor sp. nov. is restricted to Mt. Chiperone
      and distinguished by its small size, weakly-developed dorsal crenulations, and a
      large rostral process in males; Rhampholeon (Rhinodigitum) tilburyi sp. nov. is
      restricted to Mt. Namuli and distinguished by its small size, weakly-developed
      dorsal crenulations, and prominent flexure of the snout in males; and Rhampholeon
      (Rhinodigitum) bruessoworum sp. nov. is restricted to Mt. Inago and distinguished
      by its small size, weakly-developed dorsal crenulations, large rostral process in
      males, and relatively long tail in both sexes.  

PMID- 24943412
TI  - An annotated checklist and a family key to the pseudoscorpion fauna (Arachnida:
      Pseudoscorpiones) of Sri Lanka.
AB  - Sri Lanka is part of the Western Ghats & Sri Lanka biodiversity hotspot. Thus,
      the conservation of Sri Lanka's unique biodiversity is crucial. The current study
      is part of an ongoing survey of pseudoscorpion fauna of Sri Lanka. We carried out
      an island-wide survey of pseudoscorpions using a range of collection methods to
      sample a diverse set of habitats around the country. This produced 32 species,
      four of which might be new to science, belonging to 25 genera. The family
      Cheiridiidae was discovered on the island for the first time. One new
      combination, Indogarypus ceylonicus (Beier, 1973) comb. nov., is proposed. Out of
      the 47 species now recorded, 20 (43 %) are potentially endemic to Sri Lanka. We
      provide a checklist of all known species, document their distribution and give a
      key to the families. 

PMID- 24943413
TI  - A new species of wolf snake (Colubridae: Lycodon Fitzinger, 1826) from Phnom
      Samkos Wildlife Sanctuary, Cardamom Mountains, southwest Cambodia.
AB  - A new species of the genus Lycodon Fitzinger, 1826 is described from the Cardamom
      Mountains of southwest Cambodia. Lycodon zoosvictoriae distinctly differs from
      all other species of Lycodon in Southeast Asia by a combination of its
      morphometric characters and unique coloration. The new species has 17 dorsal
      scales at midbody; 2+2 temporals; 8 supralabials; 10 infralabials; loreal
      separated from internasal and orbit; 213 ventrals; 85 subcaudals; pale tan brown
      ground color; irregular dark brown blotches on anterior part, 31 transverse
      blotches on posterior part of body and 26 blotches on tail. Given its submontane
      type locality, the new species could prove to be endemic to the Cardamom
      Mountains of southwest Cambodia and probably Southeast Thailand. 

PMID- 24943414
TI  - A new Amazonian species of Cryptocellus (Arachnida, Ricinulei), with descriptions
      of its integumental structures and all free-living life stages.
AB  - A new species of Cryptocellus Westwood, 1874 is described, based on males,
      females and all free-living immature stages. Cryptocellus muiraquitan sp. nov.
      from Juruti, Para, Brazil, is a member of the foedus group of species and
      probably closely related to Cryptocellus icamiabas Tourinho & Azevedo, 2007, C.
      abaporu Bonaldo & Pinto-da-Rocha, 2003 and C. simonis Hansen & Sorensen, 1904.
      The new species is illustrated using stereomicroscopy and scanning electron
      microscopy. The large diversity of integumental structures of the new species is
      described and compared to that of previously studied species of Cryptocellus and
      Pseudocellus Platnick, 1980. 

PMID- 24943415
TI  - Revision of the genus Pteroplistes in India, with the description of two new
      species Pteroplistes kervasae Jaiswara, n. sp. and Pteroplistes masinagudi
      Jaiswara, n. sp. (Orthoptera, Grylloidea, Pteroplistinae).
AB  - Pteroplistes Brunner von Wattenwyl, 1873 is an Indo-Malaysian cricket genus with
      only one species, P. platycleis Bolivar, 1899(1900) known from India. Here, we
      redescribe the genus Pteroplistes and P. platycleis and describe two new Indian
      species, Pteroplistes kervasae Jaiswara, n. sp. and Pteroplistes masinagudi
      Jaiswara, n. sp. from the Western Ghats, using morphology and genitalia.
      Identification keys to separate the Indian species of Pteroplistes are provided
      and the distribution of the genus in India is discussed. 

PMID- 24943416
TI  - Anole classification: a response to Poe.

PMID- 24943417
TI  - A new Colombian species of Cryptocellus (Arachnida, Ricinulei), with notes on the
      taxonomy of the genus.
AB  - Cryptocellus sofiae sp. nov. is described based on males and females obtained
      from the easternmost part of Colombia, in Vichada Department. The new species is
      placed in the adisi species-group, based on the morphology of the male copulatory
      apparatus and the presence of polygonal (navicular or calyx-like) setae. With
      this addition, the group now comprises four species. A key for the identification
      of the members of this group is provided. Some taxonomic remarks about the adisi
      group and the genus Cryptocellus Westwood, 1874 are made. 

PMID- 24943418
TI  - Descriptions of unknown sexes, new geographical records, and host associations
      for two South American species of Megachile (Hymenoptera: Megachilidae).
AB  - The cosmopolitan genus Megachile include many species described on the basis of
      only one sex. Sexual dimorphism is very pronounced in these taxa and therefore
      sexes are often difficult to associate, thus making species identification nearly
      impossible. The females of M. (Chrysosarus) concava and M. (Pseudocentron)
      variplantis are described and illustrated. Additional geographical and host
      records are provided as well as comments on their diagnostic features and
      identification based on existing keys. 

PMID- 24943419
TI  - New quill mites (Cheyletoidea: Syringophilidae) parasitizing tyrannid birds
      (Passeriformes: Tyrannidae) in Peru.
AB  - Two new quill mite species (Cheyletoidea: Syringophilidae) are described from
      tyrannid birds (Passeriformes: Tyrannidae) in Peru: Picobia sayornis sp. nov.
      from the black phoebe Sayornis nigricans (Swainson) (first record of Picobia
      Haller species on tyrannid host) and Syringophilopsis szeffleri sp. nov. from the
      scale-crested pygmy-tyrant Lophotriccus pileatus (Tschudi). The Pacific elaenia
      Myiopagis subplacens (Sclater) is recorded as a new host for Syringophilopsis
      tyranni Bochkov and Galloway. 

PMID- 24943420
TI  - First description of the male of Sphecotypus niger (Perty, 1833), with notes on
      behavioral and morphological mimicry (Araneae: Corinnidae: Castianeirinae).

PMID- 24943421
TI  - A new genus and two new species of Opilioacaridae (Acari: Parasitiformes) from
      Amazonia, Brazil with a key to world genera.
AB  - Collections of Opilioacaridae made close to 50 years ago in Manaus in the
      Amazonian Region have allowed the description of a new genus and two new species
      from Brazil, Amazonacarus setosus n.gen, n.sp. and A. paraensis n.gen, n.sp.
      These species show a unique combination of characters in the Opilioacaridae: a
      high number of foliate setae (10) on the palp tarsus with each seta bearing many
      lobes (6-7), a group of large, serrate setae (26-31) on the palp tibia (this
      group of setae is much smaller in other species), and 5-7 dorsal setae on
      idiosomal segment XVIII. Indiacarus and some Opilioacarus show 3-5 setae on
      segment XVIII, but these genera (and Caribeacarus) have fewer foliate setae on
      the palp (3-4). Females of Amazonacarus have an ovipositor of the "complex" type,
      with spiny projections and 2-4 genital setae, while males have two pairs of
      rounded, large glands. 

PMID- 24943423
TI  - Review of the New Caledonian species of the genus Pactola Pascoe, 1876
      (Coleoptera: Curculionidae: Eugnomini), with description of two new species .
AB  - The two species of the genus Pactola Pascoe known from New Caledonia, P. convexa
      (Montrouzier) and P. setacea (Montrouzier), are redescribed and two new species
      (P. magna sp. n. and P. proxima sp. n.) are described. Pactola kanalensis
      (Perroud) is a new junior synonym of P. setacea (Montrouzier). A neotype of
      Pactola setacea (Montrouzier) and lectotypes of Pactola convexa (Montrouzier) and
      Pactola kanalensis (Perroud) are designated. Pactola nigra Hudson is considered
      conspecific with Pactola variabilis Pascoe but formal synonymy requires further
      study. Colour photographs of the dorsal habitus and line drawings of
      taxonomically relevant structures of all species are provided, as well as an
      identification key to all known species of Pactola. 

PMID- 24943422
TI  - Descriptions of two new, cryptic species of Metasiro (Arachnida: Opiliones:
      Cyphophthalmi: Neogoveidae) from South Carolina, USA, including a discussion of
      mitochondrial mutation rates.
AB  - Specimens of Metasiro from its three known disjunct population centers in the
      southeastern US were examined and had a 769 bp fragement of the mitochondrial
      gene cytochrome c oxidase subunit I (COI) sequenced. These populations are
      located in the western panhandle of Florida and nearby areas of Georgia, in the
      Savannah River delta of South Carolina, and on Sassafras Mt. in South Carolina.
      This range extends over as much as 500 km, which is very large for a species of
      cyphophthalmid harvestmen and presents a degree of physical separation among
      populations such that we would expect them to actually be distinguishable
      species. We examined the morphology, including the spermatopositors of males, and
      sequences from 221 specimens. We found no discernible differences in the
      morphologies of specimens from the different populations, but corrected pairwise
      distances of COI were about 15% among the three population centers. We also
      analyzed COI data using a General Mixed Yule Coalescent (GMYC) model implemented
      in the R package SPLITS; with a single threshold, the most likely model had four
      species within Metasiro. Given this level of molecular divergence, the monophyly
      of the population haplotypes, and the number of exclusive COI nucleotide and
      amino acid differences distinguishing the populations, we here raise the Savannah
      River and Sassafras Mt. populations to species status: M. savannahensis sp. nov.,
      and M. sassafrasensis sp. nov., respectively. This restricts M. americanus
      (Davis, 1933) to just the Lower Chattahoochee Watershed, which in this study
      includes populations along the Apalachicola River and around Florida Caverns
      State Park. GMYC models reconstructed the two main haplotype clades within M.
      americanus as different species, but they are not exclusive to different areas.
      We estimate COI percent divergence rates in certain cyphophthalmid groups and
      discuss problems with historical measures of this rate. We hypothesize that
      Metasiro began diversifying over 20 million years ago. 

PMID- 24943424
TI  - Taxonomic revision of the Australian arid zone lizards Gehyra variegata and G.
      montium (Squamata, Gekkonidae) with description of three new species.
AB  - The taxonomy of central Australian populations of geckos of the genus Gehyra has
      been uncertain since chromosomal studies carried out in the 1970s and 1980s
      revealed considerable heterogeneity and apparently independent patterns of
      morphological and karyotypic diversity. Following detailed molecular genetic
      studies, species boundaries in this complex have become clearer and we here re
      set the boundaries of the three named species involved, G. variegata (Dumeril &
      Bibron, 1836), G. montium Storr, 1982, and G. nana King, 1982, and describe three
      new species. Two of the new species, G. moritzi and G. pulingka, include
      populations formerly assigned to either G. montium or G. nana Storr, 1982, while
      the third, G. versicolor, includes all of the eastern Australian populations
      formerly assigned to G. variegata. 

PMID- 24943425
TI  - Six new species of Hylotribus Jekel, 1860 from Brazil (Coleoptera, Anthribidae,
      Anthribinae, Discotenini).
AB  - Hylotribus Jekel, 1860 is a distinct genus of South American Anthribidae
      characterized by a fragmented antebasal pronotal carina, and includes nine
      species, eight of which are endemic to Chile, and one species from Peru. We here
      describe and illustrate six new species from the Atlantic Rainforest biome in
      Brazil based on unidentified material deposited in various collections:
      Hylotribus fluminensis Queiroz & Mermudes sp. nov. (Rio de Janeiro, Rio de
      Janeiro State); Hylotribus sublimis Queiroz & Mermudes sp. nov. (Campos do
      Jordao, Sao Paulo State); Hylotribus plaumanni Queiroz & Mermudes sp. nov.
      (Seara, Santa Catarina State); Hylotribus frontispeltastes Queiroz & Mermudes sp.
      nov. (Sao Jose do Barreiro, Serra da Bocaina, Sao Paulo State and Serra do
      Caraca, Minas Gerais State); Hylotribus gauchus Queiroz & Mermudes sp. nov.
      (Cambara do Sul, Rio Grande do Sul State); and Hylotribus involucer Queiroz &
      Mermudes sp. nov. (Sao Jose do Barreiro, Serra da Bocaina, Sao Paulo State). A
      key is provided to the species of Hylotribus in Brazil. 

PMID- 24943426
TI  - A new species of Heterangaeus Alexander, 1925 crane flies (Diptera: Pediciidae)
      from north-central Mongolia with first description of the larva for the genus.
AB  - A new species of Pediciidae, Heterangaeus mongolicus is described from specimens
      collected during the fieldwork of the Mongolian Aquatic Insect Survey Project in
      north-central Mongolia, Tov Aimag (district). Descriptions and illustrations of
      the distinguishing morphological features are provided. Habitat information is
      presented. Female ovipositor and larvae of Heterangaeus are described and
      illustrated for the first time. This discovery of Heterangaeus in Mongolia
      represents a 1700 kilometer extension of the known distribution for the genus. 

PMID- 24943427
TI  - A new Bradyporus Charpentier, 1825 species from Iran (Orthoptera, Bradyporinae).
AB  - The species of Bradyporus Charpentier, 1825 found in Turkey has been revised by
      the second author (M. Unal, 2011). Bradyporus comprises thirteen species and
      subspecies at present. The species of the genus have a range of Central
      Palaearctic distribution; most of the species are Balkanian-Anatolian-Iranian,
      whereas some of them are restricted to Ukraine, the Caucasus, Transcaucasus,
      being inhabitants in the continental mountain steppe belt. It seems that
      Anatolia, with 8 species, and Balkans, with 6 species, are two diversity centres
      of this genus. Iran represented by only species, B. latipes (Stal, 1875). But,
      one more peculiar species is described from north west of Iran herein. The
      species of this genus are very similar to one another in their external features,
      however, detailed descriptions and characterizations are given for the authentic
      separation of the known species in the exhausting revision of the genus by the
      second author (Unal, 2011). 

PMID- 24943428
TI  - Taxonomic study of the genus Assara Walker (Lepidoptera, Pyralidae, Phycitinae)
      in NE China, with description of a new species.
AB  - Four species of the genus Assara Walker, 1863 are revised from NE China. Among
      them, Assara yanbianensis Bae & Qi sp. n. is described as new to science and A.
      terebrella (Zincken, 1818) is newly recorded from China. A key to the NE Chinese
      species of the genus Assara with illustrations of adults and genitalia are
      presented. 

PMID- 24943430
TI  - Reading trees.

PMID- 24943429
TI  - A new species of Syndicus (s. str.) Motschulsky (Coleoptera, Staphylinidae,
      Scydmaeninae) from East China.
AB  - Syndicus (s. str.) jaloszynskii Yin and Song, new species is described from
      Fujian and Zhejiang, East China. All material was collected in rotten woods. The
      habitus of both sexes, aedeagus, and spermatheca are illustrated. The new species
      can be readily separated from all known congeners by the strikingly large body
      size, the structure of aedeagal endophallus, and the form of spermatheca. This is
      the first species of the nominotypical subgenus of Syndicus known to occur in
      China. 

PMID- 24943431
TI  - Description of two new species of Arcania Leach, 1817, from the western Pacific
      Ocean and redescriptions of A. undecimspinosa De Haan, 1841, and A. elongata
      Yokoya, 1933 (Crustacea: Brachyura: Leucosiidae).
AB  - Arcania undecimspinosa De Haan, 1841, and A. elongata Yokoya, 1933, are
      redescribed, with a lectotype of A. undecimspinosa formally designated.
      Redescription of the two species revealed that there are several specimens and
      possible undescribed species that have been inaccurately recorded under the name
      of A. undecimspinosa and A. elongata. Two such species are described from the
      western and southern Pacific Ocean as new to science. These four species
      partially overlap their geographical distributions and are superficially similar
      to each other, but the present study shows that there are clear differences in
      the shapes of their male first gonopods, female vulvae, frontal lobes of the
      carapace and other morphological characters. Literature that cited A.
      undecimspinosa s.l. is also reviewed to highlight possible taxonomic problems. 

PMID- 24943432
TI  - Subfamily Limoniinae Speiser, 1909 (Diptera, Limoniidae) from Baltic amber
      (Eocene): the genus Helius Lepeletier & Serville, 1828.
AB  - A revision of the genus Helius Lepeletier & Serville, 1828 (Diptera: Limoniidae)
      from Baltic amber (Eocene) is presented. Redescriptions of 5 species, Helius
      formosus Krzeminski, 1993, Helius linus Podenas, 2002, Helius minutus (Loew,
      1850), Helius mutus Podenas, 2002, Helius pulcher (Loew, 1850) of this genus from
      Baltic amber are given and documented by photographs and drawings. Four new
      species of the genus Helius from Baltic amber are described: Helius gedanicus sp.
      nov., Helius hoffeinsorum sp. nov., Helius similis sp. nov., Helius fossilis sp.
      nov. A key to species of Helius from Baltic amber is provided. Patterns
      morphological evolution and the aspects evolutionary history of Helius are
      discussed. 

PMID- 24943433
TI  - Two new subterranean species of Hyalella Smith, 1874 (Crustacea: Amphipoda:
      Hyalellidae) from Brazil.
AB  - Two new species of Hyalella from Brazil are described. Hyalella veredae sp. n.
      shows the following characters: eyes reduced or absent in some specimens; antenna
      1 and antenna 2 of similar size, and a curved seta on the inner ramus of male
      uropod 1. Hyalella formosa sp. n. is characterized by the absence of eyes,
      antenna 1 longer than antenna 2 and a curved seta on the inner ramus of male
      uropod 1. The species were found on caves located in two private properties, both
      under the impact of agricultural activities, which demonstrates a potential
      threat to these subterranean environments. 

PMID- 24943434
TI  - Description of a new genus and three species of Encyrtidae (Hymenoptera:
      Chalcidoidea) from the Western Ghats of Karnataka, India.
AB  - A new genus of Encyrtidae (Hymenoptera: Chalcidoidea), Noyesencyrtus Singh gen.
      nov. (type species N. brachyoculus Singh sp. nov.), associated with insects
      inhabiting fruiting bodies of wood-decaying fungi, and two new species,
      Psyllaephagus kundapurensis Singh sp. nov. and Ooencyrtus hayatii Singh sp. nov.,
      are described from the Western Ghats of Karnataka, India. 

PMID- 24943435
TI  - The genera Anafroptilum Kluge, 2011 and Neocloeon Traver, 1932, reinstated
      status, in North America, with remarks about the global composition of
      Centroptilum Eaton, 1869 (Ephemeroptera: Baetidae).
AB  - The mayfly genus Centroptilum Eaton, 1869, s.s., (Ephemeroptera: Baetidae), as
      presently understood, is not known to occur in North America. Nearctic species
      recently classified there belong either to Anafroptilum Kluge, 2011 or to
      Neocloeon Traver, 1932, reinstated genus. The North American endemic Neocloeon
      differs fundamentally from Anafroptilum in that it possesses a patella-tibial
      suture on the foreleg of larvae and female adults, a characteristic that is
      shared with certain other baetid genera. Neocloeon includes the obligate
      parthenogen N. triangulifer, new combination, and a sexual species, N. alamance,
      reinstated combination. Nearctic Anafroptilum include: A. album (McDunnough,
      1926), new combination, A. asperatum (Traver, 1935), new combination, A.
      bifurcatum (McDunnough, 1924), A. conturbatum (McDunnough, 1929), new
      combination, A. minor (McDunnough, 1926), new combination, A. ozarkense (Wiersema
      & Burian, 2000), new combination, A. semirufum (McDunnough, 1926), new
      combination, and A. victoriae (McDunnough, 1938), new combination. Further study
      will be required to determine the species composition of Anafroptilum and
      Centroptilum, s.s., in the Palearctic and Oriental realms. Anafroptilum and
      Neocloeon are part of the Cloeon complex of genera, but Centroptilum, s.s., is
      not. 

PMID- 24943436
TI  - Flea weevils of the genus Megorchestes Kojima (Coleoptera, Curculionidae,
      Curculioninae, Rhamphini), with description of a second species from India.
AB  - A second species of Megorchestes Kojima, M. deccanensis sp. nov., is described
      from India and a key to the two species is provided. 

PMID- 24943437
TI  - A new species of Leydigia Kurz, 1875 (Cladocera: Chydoridae) from Colombia.
AB  - A new species of Leydigia Kurz, 1875 (Cladocera: Chydoridae) is described based
      on the material from Cienaga Grande de Santa Marta, Magdalena Department,
      Colombia. L. lourdesae sp. nov. is a member of the subgenus Leydigia
      (Neoleydigia) Kotov, 2009, having all diagnostic characters of the latter. It
      could be the closest relative to L. iberica Kotov & Alonso, 2010, having five
      setae on exopodite III, a unique for the genus character. But new taxon differs
      from the latter in a series of characters of the head pores, armature of valve
      ventral margin, postabdomen, antenna I and II, and limbs I-III. We believe that
      the basal taxa of L. (Neoleydigia) (including L. lourdesae sp. nov.) are remains
      of an antique pan-continental group, probably of Mesozoic age, partly survived
      after the mass extinction and represented now by a series of locally distributed
      taxa in very distant localities of the planet. 

PMID- 24943438
TI  - A remarkable new species of Paraphamartania Engel from Portugal (Diptera,
      Asilidae).
AB  - Paraphamartania marvaoensis sp. nov. is described based on three male and one
      female specimens from Marvao, Portugal. The discovery of this new species of
      Paraphamartania is of great significance since it shows the occurrence of a
      second species of Paraphamartania in the western Mediterranean. High resolution
      pictures of type material of all three species of Paraphamartania are provided
      together with a key to these three species. DNA barcodes of this new species are
      provided, so future workers are able to study relationships of Paraphamartania. 

PMID- 24943439
TI  - Dressed in black. A New Ansonia Stoliczka, 1870 (Lissamphibia: Anura: Bufonidae)
      from Gunung Murud, Sarawak, East Malaysia (Borneo).
AB  - A new species of stream toad of the genus Ansonia is described from Gunung Murud,
      Pulong Tau National Park, of northern Sarawak, Malaysia, Borneo. Ansonia vidua,
      sp. nov., is morphologically distinguished from its Bornean congeners by the
      following combination of characters: medium size (SVL of adult females 33.5-34.4
      mm); body uniformly black-brown in life; absence of a visible pattern on dorsum
      or limbs; presence of two low interorbital ridges; shagreened skin on dorsum,
      sides and upper surfaces of the limbs with numerous homogeneously small, rounded
      warts; first finger shorter than second; reduced webbing between the toes and an
      absence of a sharp tarsal ridge. Uncorrected genetic distances between related
      taxa of > 4.3% in 16S rRNA gene support its status as a hitherto undescribed
      species. 

PMID- 24943440
TI  - New fossil Praeaulacinae wasps (Insect: Hymenoptera: Evanioidea: Praeaulacidae)
      from the Middle Jurassic of China.
AB  - A new genus with a new species, Archaulacus probus gen. et sp. nov., and two new
      species, Praeaulacus subrhombeus sp. nov., P. tenellus sp. nov., belonging to the
      subfamily Praeaulacinae (Praeaulacidae) are described and illustrated. The
      specimens were collected from the Middle Jurassic of Jiulongshan Formation at
      Daohugou in Inner Mongolia, China. Archaulacus gen. nov. differs from other
      genera of Praeaulacinae in having the first abscissa of Rs of the fore wing
      subvertical to R and 2m-cu slightly basad of 2r-m. This is the first time that
      these characters are reported for the Praeaulacinae. Based on new information
      provided by the new species, an updated key to the known species of Praeaulacus
      is provided. 

PMID- 24943442
TI  - Two new desma-less species of Theonella Gray, 1868 (Demospongiae: Astrophorida:
      Theonellidae), from the Great Barrier Reef, Australia,and a re-evaluation of one
      species assigned previously to Dercitus Gray, 1867.
AB  - Extensive surveys of the biodiversity on the seafloor of the inter-reef regions
      of the Great Barrier Reef, Australia, have resulted in the collection of large
      numbers of sponges, many of which are likely new to science. Identification of
      these sponges, however, was made difficult by the absence in some specimens of
      key diagnostic characters, such as megascleres. We used an integrated approach to
      the taxonomy of these sponges, incorporating morphological examination by SEM,
      analysis of DNA sequence data (using the COI barcoding fragment of mtDNA) and
      preliminary studies of the chemistry of the sponges, to describe the new species,
      which were found to contain no native spicules other than acanthose microrhabds.
      Here, we propose two new species of Theonella Gray, 1868: Theonella deliqua n.
      sp. (found in association with a single unidentified species of siliquariid
      mollusc) and Theonella maricae n. sp. from the Great Barrier Reef. Further, we
      propose the new combination of Theonella xantha (Sutcliffe, Hooper and Pitcher
      2010) n. comb. for another microrhabd-only-bearing species. On the basis of our
      gene trees, we recognise Theonella (and Theonellidae Lendenfeld, 1903) within
      Astrophorida Sollas, 1887. We discuss the potential for chemotaxonomic and DNA
      based insights into the origins and radiation of species of Theonella and explore
      the evolutionary significance of the reduced morphology of the three additional
      species recognised here. 

PMID- 24943441
TI  - New species of Eibesfeldtphora Disney (Diptera: Phoridae) and a new key to the
      genus.
AB  - Two new species of parasitoids, Eibesfeldtphora trifurcata and Eibesfeldtphora
      inornata, are described. Both species were collected in Brazil. A new key is
      provided and illustrated for the twenty one known species. 

PMID- 24943443
TI  - Four new Paramphimonhystrella species (Nematoda: Xyalidae) from the continental
      slope of New Zealand.
AB  - Four new Paramphimonhystrella species are described from the continental slope of
      New Zealand. P. glossalga n. sp. is characterised by presence of twelve lips,
      large buccal cavity, males with short, heavily cuticularised spicules joined
      distally, and females with large postvulvar sac and hammer-shaped cuticularised
      piece immediately posterior to vagina. P. barbula n. sp. is characterised by
      narrow buccal cavity, oval-shaped amphids, conico-cylindrical tail with swollen
      appearance due to conspicuously enlarged caudal gland, and males with long
      slender spicules and small gubernaculum. P. scutula n. sp. is characterised by a
      lozenge-shaped buccal cavity, males with scythe-shaped spicules, females with
      vulva at almost two thirds of body length from anterior, and a hammer-shaped
      cuticularised piece immediately posterior to vagina. P. echinocauda n. sp. is
      characterised by buccal cavity with cylindrical anterior portion and funnel
      shaped posterior portion, distal tip of slender spicules with three pointed
      projections, thin gubernaculum, and tail with several long setae in middle
      portion, two lateral setae near tail tip and one terminal seta. The presence of a
      hammer-shaped cuticularised piece in two species of the genus is recorded for the
      first time; the function of this structure is unknown. The genus diagnosis is
      emended and a key to all known Paramphimonhystrella species (seven in total) is
      provided. The present study provides the first record of the genus outside the
      type locality (Yellow Sea) and extends its depth distribution from <150 m to 1350
      m. 

PMID- 24943444
TI  - Tydeid and triophtydeid mites (Acari: Tydeoidea) associated with grapevine
      (Vitaceae: Vitis spp.) in Brazil, with the descriptions of species of Prelorryia
      (Andre, 1980) and Tydeus Koch, 1835.
AB  - We report on the Tydeidae and Triophtydeidae associated with grapevine (Vitis
      labrusca L. and Vitis vinifera L.) in Rio Grande do Sul State, Brazil, and
      describe a new species of Prelorryia, Prelorryia labrusca sp. nov., and two new
      species of Tydeus, Tydeus manoi sp. nov. and Tydeus riopardensis sp. nov.
      Brachytydeus formosa (Cooreman), B. podocarpa (Baker), Neolorryia pandana
      (Baker), Tydeus californicus (Banks), Pretydeus henriandrei Kazmierski and
      Triophtydeus lebruni (Andre) are recorded and illustrated. A key to species of
      Tydeidae and Triophtydeidae from Brazil is provided.  

PMID- 24943445
TI  - Contributions to the taxonomy and faunistics of some arctic species of Spilogona
      Schnabl (Diptera: Muscidae).
AB  - New synonymies in the genus Spilogona Schnabl, 1911 are proposed: S.
      novaesibiriae (Frey, 1915) = S. obsoleta (Malloch, 1920), syn. nov.; S.
      trianguligera (Zetterstedt, 1838) = S. setinervis (Huckett, 1932), syn. nov.
      Spilogona trianguligera and S. tendipes (Malloch, 1920) are newly recorded from
      Greenland, and S. trianguligera also from W Siberia. The female of S. vikhrevi
      Sorokina, 2010 is described and the species in newly recorded from Wrangel Island
      (Far East Russia). 

PMID- 24943446
TI  - Taxonomy of the genus Erymus Bordoni (Coleoptera: Staphylinidae, Staphylininae,
      Xantholinini) in China with descriptions of two new species.
AB  - This paper studies the taxonomy of the genus Erymus Bordoni, 2002 (Coleoptera:
      Staphylinidae, Staphylininae, Xantholinini) from China. Two new species are
      described: Erymus wufengensis sp. n. from Hubei, and E. gilvus sp. n. from
      Hainan, Guangxi, and Guangdong provinces of China. The previously known four
      species of this genus are redescribed, and the identification key to all six
      Chinese species of the genus is provided. The type specimens of the new species
      are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZ-CAS). 

PMID- 24943447
TI  - The Lonchaeidae of fiji (Diptera: schizophora) .
AB  - The status of the family Lonchaeidae on the islands of the Fiji group is
      reviewed. Data are provided from trapping undertaken as part of the NSF-Fiji
      Terrestrial Arthropod Survey and from Fijian Lonchaeidae in the collections of
      the Bishop Museum, Hawaii and the Natural History Museum, London. Five new
      species, Lonchaea fiji sp. nov., Lonchaea melanesia sp. nov., Lonchaea vanua sp.
      nov., Silba kadavu sp. nov. and Silba setiphallus sp. nov. are described. Two
      species new to Fiji, Dasiops ruidifrons McAlpine, 1964 amd Lamprolonchaea
      lustrata McAlpine, 1964, are recorded. Five species previously recorded,
      Lamprolonchaea brouniana (Bezzi, 1919), Lamprolonchaea smaragdi (Walker, 1849),
      Lonchaea cyaneoneitens Kertesz, 1901, Silba calva (Bezzi, 1913) and Silba
      setifera (de Meijere, 1910) are re-evaluated and are removed from the checklist.
      The fauna is now considered to comprise of 11 species in 4 genera. A key is
      provided to the Lonchaeidae present on the islands. 

PMID- 24943448
TI  - New species of Sinella and Coecobrya (Collembola: Entomobryidae) from New
      Caledonia.
AB  - The genera Sinella and Coecobrya are reported from New Caledonia for the first
      time, with four new species: Sinella quadriseta sp. nov., S. claviseta sp. nov.,
      S. copiosa sp. nov., and Coecobrya neocaledonica sp. nov. Sinella species studied
      here exhibit several morphological features that are not found in other non-cave
      species of the genus: paired teeth on inner edge of unguis closer to the base and
      distal unpaired tooth very tiny or absent, 2 medio-medial and 1 medio-lateral
      macrochaetae on Th. II, 2+2 lateral macrochaetae on Abd. III, and abundant short
      S-chaetae on Abd. IV. The four S-chaetae present on Abd. V are also different
      from the common pattern in Entomobryidae. C. neocaledonica sp. nov. does not
      exhibit unique features different from Coecobrya species of other areas. 

PMID- 24943449
TI  - Revision of the cranaid genera Phalangodus, Iquitosa and Aguaytiella (Opiliones:
      Laniatores: Gonyleptoidea).
AB  - The monotypic genus Temucus Roewer, 1943, originally placed in Pachylinae
      (Gonyleptidae) is transferred to the Cranainae (Cranaidae) and synonymized with
      Phalangodus Gervais, 1842, therefore Phalangodus palpiconus (Roewer, 1943) comb.
      nov. is proposed. The synonymy is based on the following features: (i) the
      outline of dorsal scutum type alpha; (ii) the thickened pedipalpal claw in males;
      (iii) pedipalpal femur with a few ventral enlarged tubercles restricted to the
      median ventral region, and a conspicuous group of very large and acuminated
      tubercles basally; (iv) ventral plate of penis with a rather elevated number of
      cylindrical, straight and sharp distal pairs of setae and a notorious reduction
      in the number of the basal pairs of setae; (v) penis stylus straight, its distal
      tip rounded in a mushroom-like shape without stylar caps. The record of P.
      palpiconus to Chile is doubtful. We also propose the revalidation of Iquitosa
      Roewer, 1943, hitherto considered a junior synonym of Phalangodus. Iquitosa is
      revised and the male of its type species, I. poecilis, is reported for the first
      time. Aguaytiella Goodnight & Goodnight, 1943, a monotypic genus which
      superficially resembles Iquitosa is also revised. In this article, we report data
      of male genitalia of Iquitosa and Aguaytiella, providing redescriptions and
      diagnoses of those genera and species, and a discussion of their relationship
      with other cranaids. 

PMID- 24943450
TI  - The neotropical flower-living genus Lenkothrips (Thysanoptera, Heterothripidae):
      three new species and an identification key.
AB  - Three new species are described in the South American genus of flower-feeding
      thrips, Lenkothrips De Santis & Sureda: L. mollinediae sp. n. from four species
      of Mollinedia (Monimiaceae) in Brazil and Ecuador; L. guaraniticus sp. n. and L.
      kaminskii sp. n. from Malpighiaceae in Brazil. An illustrated key to the five
      Lenkothrips species now recognized is provided. 

PMID- 24943451
TI  - Studies on Megachile Latreille subgenus Callomegachile Michener (Hymenoptera:
      Megachilidae) from Chandigarh and Haryana plains, India.
AB  - Floral associations of three species of Megachile (Callomegachile) from NW India
      are provided: M. (C.) disjuncta, M. (C.) cephalotes and M. (C.) lerma.
      Morphological characters of both sexes and the male genitalia of each species are
      presented and illustrated. All three species are new records for Union Territory
      (Chandigarh) and Haryana in India. 

PMID- 24943453
TI  - Quantitative determination of protein molecular weight with an acoustic sensor;
      significance of specific versus non-specific binding.
AB  - Surface acoustic wave sensors with integrated microfluidics for multi-sample
      sensing have been implemented in this work towards the quantitative correlation
      of the acoustic signal with the molecular weight of surface bound proteins
      investigating different interaction/binding conditions. The results are presented
      for: (i) four different biotinylated molecules (30 <= Mw <= 150 kDa) specifically
      binding to neutravidin; (ii) the same four non-biotinylated molecules, as well as
      neutravidin, adsorbing onto gold; and (iii) four cardiac marker proteins (86 <=
      Mw <= 540 kDa) specifically binding to their homologous antibodies. Surface
      plasmon resonance was employed as an independent optical mass sensor. A linear
      relationship was found to exist between the phase change of the acoustic signal
      and the molecular weight of the proteins in both cases of specific binding. In
      contrast, non-specific binding of proteins directly onto gold exhibited no such
      linear relationship. In all three cases phase change was correlated with the
      bound mass per area. The underlying mechanism behind the different behavior
      between specific and non-specific binding is discussed by taking into account the
      geometrical restrictions imposed by the size of the specific biorecognition
      molecule and the corresponding bound protein. Our results emphasize the
      quantitative nature of the phase of the acoustic signal in determining the Mw (in
      the case of specific binding) with a resolution of 15% and the mass of the bound
      proteins (in all cases), as well as the significance of the biorecognition
      molecules in deriving the molecular weight from acoustic or optical detectors. 

PMID- 24943454
TI  - Cannot intubate cannot ventilate-focus on the 'ventilate'.

PMID- 24943457
TI  - Taming the cancer cell.

PMID- 24943455
TI  - Effect of three peptidase inhibitors on antinociceptive potential and toxicity
      with intracerebroventricular administration of dynorphin A (1-17) or (1-13) in
      the rat.
AB  - PURPOSE: The N- and C-terminal regions of dynorphin (Dyn) A (1-17) activate
      opioid and N-methyl-D-aspartate receptors, respectively. Earlier studies
      demonstrated that Dyn-converting enzyme cleaved Dyn A (1-17) mainly at the Arg(6)
      Arg(7) bond, resulting in the production of N- and C-terminal region peptide
      fragments, and that this enzyme was not inhibited by a mixture of the three
      peptidase inhibitors (PIs) amastatin (A), captopril (C), and phosphoramidon (P).
      The purpose of the present study was to evaluate antinociceptive potential and
      toxicity with intracerebroventricular administration of Dyn A (1-17) or (1-13)
      under pretreatment with a mixture of A, C, and P and/or Dyn-converting enzyme
      inhibitor (p-hydroxymercuribenzoate). METHODS: Peptide fragments from Dyn A (1
      17) following incubation with membrane preparation under pretreatment with a
      mixture of the three PIs was identified by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometer (MALDI-TOF-MS). Infusion of drugs and
      peptides into the third ventricle in rats was performed via indwelling cannulae.
      Induction of antinociception and toxicity by Dyn A (1-17), Dyn A (1-13), Dyn A (1
      6), or Dyn A (7-17) were determined by the tail-flick test and induction of
      barrel rotation, respectively. The effects of the PIs on antinociception and
      toxicity were evaluated by a dose-response study and a comparison of differences
      among various combinations of Dyn A (1-17) or Dyn A (1-13) and the three PIs and
      p-hydroxymercuribenzoate. RESULTS: MALDI-TOF-MS analysis identified Dyn A (1-6)
      and Dyn A (1-10) fragments as products following incubation of Dyn A (1-17) with
      membrane preparation of rat midbrain under pretreatment with a mixture of the
      three PIs. Pretreatment with a mixture of the three PIs produced an approximately
      30-fold augmentation in antinociception induced by low-dose
      intracerebroventricular administration of Dyn A (1-17) or (1-13) in a MU-, delta-
      and kappa-opioid receptor antagonist-reversible manner, but without signs of
      toxicity such as barrel rotation in the rat. Dyn A (1-17)-induced antinociception
      and toxicity was greater than that of Dyn A (1-6), Dyn A (1-13), or Dyn A (7-17)
      at the same dose. Dyn A (1-17)-induced antinociception and toxicity under
      pretreatment with various combinations of the three PIs and p
      hydroxymercuribenzoate was greater than that with a mixture of the three PIs
      alone. CONCLUSION: These findings suggest that administration of a mixture of the
      three PIs increases Dyn A (1-17)- or (1-13)-induced antinociception under
      physiological conditions without toxicity.

PMID- 24943458
TI  - Root canal morphology of Chalcolithic and early bronze age human populations of
      El Mirador Cave (Sierra de Atapuerca, Spain).
AB  - This study provides a morphological characterization of the inner anatomy of the
      root canals of permanent first and second molars in Chalcolithic and early Bronze
      Age human fossils using cone-beam computed tomography. The general evolutionary
      trend in present-day human dentition is related to morphological simplification.
      As little is known about when this trend appeared in Homo sapiens populations,
      the aim of this work is to test the presence of modern radicular morphology 4,400
      years ago. Fifty-four permanent first and second maxillary and mandibular molars
      of 17 individuals were included in the study. All maxillary first and second
      molars showed three separate roots. Almost all the lower molars analyzed (100% of
      first molars and 75% of second molars) had two separate roots. More differences
      in the canal system configuration were documented in the maxillary mesiobuccal
      roots than in the palatal or distobuccal roots. The most variable tooth in root
      and canal configuration is the maxillary second molar. It should be pointed out
      that 12.5% of the teeth analyzed showed a C-shaped root configuration.

PMID- 24943460
TI  - Clinical importance of impingement deformities for hip osteoarthritis progression
      in a Japanese population.
AB  - PURPOSE: Femoroacetabular impingement is a new disease concept for hip disorders
      in young adults suggested as a major cause of primary hip osteoarthritis in
      Western countries. However, significant controversy exists regarding the
      prevalence and contribution of impingement deformities to osteoarthritis in
      Japan, owing to the higher prevalence of developmental dysplasia of the hip.
      Therefore, the aims of this study were to: (1) determine the prevalence of
      structural abnormalities associated with hip disorders in patients undergoing
      total hip replacement and (2) analyse the contribution of impingement deformities
      to osteoarthritis. METHODS: We analysed 250 patients from two different medical
      centres who underwent primary total hip replacement except those which were due
      to femoral head necrosis, posttraumatic osteoarthritis and systemic inflammatory
      disease. The average patient age at surgery was 64 years (range, 40-89 years),
      with 35 men and 215 women. RESULTS: Radiographic abnormality related to
      developmental dysplasia of the hip was associated with the majority of
      osteoarthritic hips (62%). Hips with femoroacetabular impingement deformities
      were present within the cases categorized as unknown etiology. Cam impingement
      deformity was present in 22% of unknown aetiology cases when cases with reactive
      osteophytes were excluded from all cam deformity cases (pistol grip deformity and
      aspherical femoral heads). CONCLUSIONS: The prevalence of femoroacetabular
      impingement within primary osteoarthritis cases and gender predominance of
      impingement deformities are relatively similar to those reported previously in
      Western populations. This finding indicates that femoroacetabular impingement
      deformities are associated with osteoarthritis in the Japanese population,
      although it has a lower frequency among all hip failure patients.

PMID- 24943461
TI  - Prospective cohort study of six hundred and sixty four revisions of loose failed
      acetabular implants.
AB  - PURPOSE: The purpose of the study was to determine the optimal technique of
      revision surgery according to the deficiency of acetabular bone to ensure maximum
      survival of the implant and reduce the risk of complications. METHODS: From
      January 1992 through May 2012, 664 revisions of failed acetabular total hip
      components were performed in the joint replacement department of the Moscow
      Central Scientific and Research Institute (CITO). The patients were divided into
      three major groups based on the type of the revision implant: group I--cemented
      polyethylene cups only, group II--acetabular cages and rings, and group III--non
      cemented metal cups. In each of these groups, further subdivisions were made
      based on the Paprosky Classification of the acetabular defects. Failures were
      classified as early mechanical instability, chronic pain, and deep wound
      infection. RESULTS: The most satisfactory results--91% were obtained in patients
      of groups I and III with relatively minor bony acetabular defects (Paprosky
      classification types 1, 2A and 2B). The most unsatisfactory results--25% were in
      the cases with greater bone loss (Paprosky classification type 3B in group I and
      type 2C in group III)-of the unsatisfactory results. Infection was a significant
      problem in all the groups, but was the highest (8%) in group II. CONCLUSIONS: The
      study showed that the success of acetabular revisions was directly related to the
      severity of the bony defects at the time of the operation and to the
      reconstruction technique applied.

PMID- 24943462
TI  - Blood volume fraction imaging of the human lung using intravoxel incoherent
      motion.
AB  - PURPOSE: To present a technique for non-contrast-enhanced in vivo imaging of the
      blood volume fraction of the human lung. The technique is based on the intravoxel
      incoherent motion (IVIM) approach. However, a substantial novelty is introduced
      here: the need for external diffusion sensitizing gradients is eliminated by
      exploiting the internal magnetic field gradients typical of the lung tissue, due
      to magnetic susceptibility differences at air/tissue interfaces. MATERIALS AND
      METHODS: A single shot turbo spin-echo sequence with stimulated-echo preparation
      and electrocardiograph synchronization was used for acquisition. Two images were
      acquired in a single breath-hold of 10 seconds duration: one reference image and
      one blood-suppressed image. The blood volume fraction was quantified using a two
      compartment signal decay model, as given by the IVIM theory. Experiments were
      performed at 1.5T in eight healthy volunteers. RESULTS: Values of the blood
      volume fraction obtained within the lung parenchyma (36 +/- 16%) are in good
      agreement with previous reports, obtained using contrast-enhanced magnetic
      resonance angiography (33%), and show relatively good reproducibility.
      CONCLUSION: The presented technique offers a robust way to quantify the blood
      volume fraction of the human lung parenchyma without using contrast agents. Image
      acquisition can be accomplished in a single breath-hold and could be suitable for
      clinical applications on patients with lung diseases. J. Magn. Reson. Imaging
      2015;41:1454-1464. (c) 2014 Wiley Periodicals, Inc.

PMID- 24943459
TI  - HOP2-MND1 modulates RAD51 binding to nucleotides and DNA.
AB  - The HOP2-MND1 heterodimer is required for progression of homologous recombination
      in eukaryotes. In vitro, HOP2-MND1 stimulates the DNA strand exchange activities
      of RAD51 and DMC1. We demonstrate that HOP2-MND1 induces changes in the
      conformation of RAD51 that profoundly alter the basic properties of RAD51. HOP2
      MND1 enhances the interaction of RAD51 with nucleotide cofactors and modifies its
      DNA-binding specificity in a manner that stimulates DNA strand exchange. It
      enables RAD51 DNA strand exchange in the absence of divalent metal ions required
      for ATP binding and offsets the effect of the K133A mutation that disrupts ATP
      binding. During nucleoprotein formation HOP2-MND1 helps to load RAD51 on ssDNA
      restricting its dsDNA-binding and during the homology search it promotes dsDNA
      binding removing the inhibitory effect of ssDNA. The magnitude of the changes
      induced in RAD51 defines HOP2-MND1 as a 'molecular trigger' of RAD51 DNA strand
      exchange. 

PMID- 24943463
TI  - Effect of jaw opening on the stress pattern in a normal human articular disc:
      finite element analysis based on MRI images.
AB  - INTRODUCTION: Excessive compressive and shear stresses are likely related to
      condylar resorption and disc perforation. Few studies have reported the disc
      displacement and deformation during jaw opening. The aim of this study was to
      analyze stress distribution in a normal articular disc during the jaw opening
      movement. METHODS: Bilateral MRI images were obtained from the temporomandibular
      joint of a healthy subject for the jaw opening displacement from 6 to 24 mm with
      1 mm increments. The disc contour for the jaw opening at 6 mm was defined as the
      reference state, and was used to establish a two dimensional finite element model
      of the disc. The contours of the disc at other degrees of jaw opening were used
      as the displacement loading. Hyperelastic material models were applied to the
      anterior, intermediate and posterior parts of the disc. Stress and strain
      trajectories were calculated to characterize the stress/strain patterns in the
      disc. RESULTS: Both the maximum and minimum principal stresses were negative in
      the intermediate zone, therefore, the intermediate zone withstood mainly
      compressive stress. On the contrary, the maximum and minimum principal stresses
      were most positive in the anterior and posterior zones, which meant that the
      anterior and posterior bands suffered higher tensile stresses. The different
      patterns of stress trajectories between the intermediate zone and the anterior
      and posterior bands might be attributed to the effect of fiber orientation. The
      compression of the intermediate zone and stretching of the anterior and posterior
      bands caused high shear deformation in the transition region, especially at the
      disc surfaces. CONCLUSIONS: The stress and strain remained at a reasonable level
      during jaw opening, indicating that the disc experiences no injury during
      functional opening movements in a healthy temporomandibular joint.

PMID- 24943465
TI  - Spinal accessory neuropathy following dual tunneling of lead extensions for motor
      cortex stimulation.
AB  - BACKGROUND: Spinal accessory nerve (SAN) injury is a known complication of
      surgery involving the posterior cervical triangle. Because the nerve lies in a
      plane that is traversed by extension leads for neuromodulation, the SAN is at
      risk during tunneling for these procedures. METHODS: We report a 50-year-old man
      who developed spinal accessory neuropathy after tunneling of two sets of
      extension leads through his neck to connect to the pulse generator at the chest
      wall. Immediately postoperatively, he developed severe right shoulder pain and
      trapezius weakness manifested as decreased shoulder abduction and scapular
      winging. RESULTS: Electromyography 2 months later confirmed a SAN injury.
      Ultrasonography demonstrated the SAN to be angulated between the two sets of
      extension leads in the posterior cervical triangle. Operative exploration
      confirmed this finding. Neurolysis was performed and the deep extension lead was
      relocated superficial to the nerve. Postoperatively, the patient had immediate
      resolution of his shoulder pain and an improved range of motion. CONCLUSION: As
      the indications for neuromodulation continue to grow, tunneling may be performed
      more frequently. It is our belief that the second pass through the neck of a dual
      extension lead system may inadvertently be directed deeply and poses an increased
      risk to the SAN.

PMID- 24943466
TI  - A de novo designed metalloenzyme for the hydration of CO2.
AB  - Protein design will ultimately allow for the creation of artificial enzymes with
      novel functions and unprecedented stability. To test our current mastery of
      nature's approach to catalysis, a Zn(II) metalloenzyme was prepared using de novo
      design. alpha3DH3 folds into a stable single-stranded three-helix bundle and
      binds Zn(II) with high affinity using His3 O coordination. The resulting
      metalloenzyme catalyzes the hydration of CO2 better than any small molecule model
      of carbonic anhydrase and with an efficiency within 1400-fold of the fastest
      carbonic anhydrase isoform, CAII, and 11-fold of CAIII.

PMID- 24943468
TI  - Healing high-risk sternotomy incisions: interrupted suture closure and negative
      pressure wound therapy.
AB  - High-risk sternotomy incisions represent a challenge at the time of wound
      closure. We present an alternate wound closure technique that can be used in high
      risk sternotomy incisions and consists of a combination of space-obliterating
      sutures and negative pressure (suction using wound VAC) therapy.

PMID- 24943470
TI  - Clinical studies in oral allergen-specific immunotherapy: differences among
      allergens.
AB  - Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT
      appears to be effective in inducing desensitization, however, patients receiving
      OIT frequently developmild/moderate symptoms during the therapy. It has not been
      clearly established whether the clinical tolerance induced by OIT resembles
      natural tolerance. According to our data, the efficacy of OIT is different among
      food antigens, and it is comparatively difficult to achieve the clinical
      tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety
      with long-term therapy is limited. Further studies need to be offered to patients
      in clinical practice. Recently, novel treatments for food allergy, sublingual and
      epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal
      antibody (omalizumab), have been examined in some studies. OIT combined with
      omalizumab increased the threshold doses of food without adverse reactions and
      may be of benefit in food allergy treatment. More studies are needed to
      demonstrate long-term safety and treatment benefits in a larger patient cohort.

PMID- 24943469
TI  - Characteristics of prosthetic joint infections due to Enterococcus sp. and
      predictors of failure: a multi-national study.
AB  - The objective of this study was to review the characteristics and outcome of
      prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18
      hospitals from six European countries. Patients with a PJI due to Enterococcus
      sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed.
      Relevant information about demographics, comorbidity, clinical characteristics,
      microbiological data, surgical treatment and outcome was registered. Univariable
      and multivariable analyses were performed. A total of 203 patients met the
      inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the
      infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44
      (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in
      43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In
      107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95%
      CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were
      independently associated with failure. The only factor associated with remission
      was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009).
      In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed
      within the first 2 years from arthroplasty in >70% of the patients, almost 50%
      had at least one comorbidity and infections were frequently polymicrobial (54%).
      The global failure rate was 44% and patients with comorbidities, fever, and
      diagnosed within the first 2 years from arthroplasty had a poor prognosis. 

PMID- 24943471
TI  - Dabigatran anticoagulation and Stanford type A aortic dissection: not always a
      lethal coincidence?

PMID- 24943472
TI  - Physical fitness and mental health impact of a sport-for-development intervention
      in a post-conflict setting: randomised controlled trial nested within an
      observational study of adolescents in Gulu, Uganda.
AB  - BACKGROUND: Physical inactivity contributes to poor fitness and mental health
      disorders. This is of concern in post-conflict low-income settings where non
      communicable diseases are emerging and there is limited evidence for physical
      activity interventions. We examined the effects of a sport-for-development
      programme on adolescent physical fitness and mental health in Gulu, Uganda.
      METHODS: We conducted a single-blinded RCT nested within an observational study
      with three unbalanced parallel groups. Participants were able-bodied adolescents
      aged 11-14 years. The intervention comprised an 11-week voluntary competitive
      sport-for-development football league. Participants who did not subscribe for the
      intervention formed a non-registered comparison group. Boys who registered for
      the sport-for-development programme were randomly allocated to the intervention
      or wait-listed. The girls programme subscription was insufficient to form a wait
      list and all registrants received the intervention. Physical fitness was assessed
      by cardiorespiratory fitness (multi-stage fitness test), muscular power (standing
      broad jump) and body composition (BMI-for-age). Mental health was measured using
      the Acholi Psychosocial Assessment Instrument for local depression-like (DLS) and
      anxiety-like (ALS) syndromes. All randomisation was computer generated and
      assessors were masked to group allocation. An intention-to-treat analysis of
      adjusted effect size (ES) was applied. RESULTS: There were 1,462 adolescents in
      the study (intervention: boys = 74, girls = 81; wait-list: boys = 72; comparison:
      boys = 472, girls = 763). At four months follow-up there was no significant
      effect on the boys fitness when comparing intervention vs wait-listed and
      intervention vs non-registered groups. However, there was a negative effect on
      DLS when comparing boys intervention vs wait-listed (ES = 0.67 [0.33 to 1.00])
      and intervention vs non-registered (ES = 0.25 [0.00 to 0.49]). Similar results
      were observed for ALS for boys intervention vs wait-listed (ES = 0.63 [0.30 to
      0.96]) and intervention vs non-registered (ES = 0.26 [0.01 to 0.50]). There was
      no significant effect on the girls for any outcomes. CONCLUSIONS: The sport-for
      development league in this study had no impact on fitness and a negative effect
      on the mental health of participating boys. From this research, there is no
      evidence that voluntary competitive sport-for-development interventions improve
      physical fitness or mental health outcomes in post-conflict settings.

PMID- 24943473
TI  - Multiple annular plaques on both legs.

PMID- 24943474
TI  - Orthodontic retention procedures in Switzerland.
AB  - OBJECTIVE: To survey retention procedures used in orthodontic practices in
      Switzerland. MATERIAL AND METHODS: A questionnaire previously developed by
      Renkema et al. (2009) was sent to 223 Swiss orthodontists. The questionnaire
      comprised six parts, mainly containing multiple-choice questions. Information as
      to background education of the individual orthodontist, retention in general,
      frequency of different types of removable or bonded retainers that were used,
      retention pro- tocol, and the type and size of the wire used for bonded retainers
      was assessed. RESULTS: The overall response rate was 65 percent. Most
      orthodontists placed a bonded retainer in the upper and lower arch, except when
      the upper arch was expanded during treatment or when extractions were performed
      in the upper arch, in which case they placed a combination of fixed and removable
      retainers. Opinions varied with regard to how many hours the removable retainers
      should be worn and the duration of the retention phase. As far as bonded
      retainers were concerned, 87 percent of the orthodontists preferred life-long
      retention. Ninety-three percent of the orthodontists considered that the
      development of a guide- line on retention procedures would be useful.
      CONCLUSIONS: The choice of retention procedures is mostly based on orthodontists
      personal preference. A further research into the long-term effectiveness of
      individual retention protocols is needed.

PMID- 24943476
TI  - Polyoxomolybdate-supported bismuth trihalides [Mo8O26(BiX3)2](4-) (X = Cl, Br,
      I): syntheses and study of polymorphism.
AB  - Octamolybdate complexes TBA4[Mo8O26(BiX3)2] (TBA = n-tetrabutylammonium, X = Cl
      (1), Br (2), I (3)) were obtained by straightforward syntheses from TBA4[Mo8O26]
      and corresponding Bi(III) halides in MeCN. All compounds were structurally
      characterized; in all cases, {BiX3} fragments are coordinated by two oxygen atoms
      of polyoxometalate core. Occurring polymorphism is also discussed. 

PMID- 24943477
TI  - Detection of Foot-and-mouth Disease Virus RNA and Capsid Protein in Lymphoid
      Tissues of Convalescent Pigs Does Not Indicate Existence of a Carrier State.
AB  - A systematic study was performed to investigate the potential of pigs to
      establish and maintain persistent foot-and-mouth disease virus (FMDV) infection.
      Infectious virus could not be recovered from sera, oral, nasal or oropharyngeal
      fluids obtained after resolution of clinical infection with any of five FMDV
      strains within serotypes A, O and Asia-1. Furthermore, there was no isolation of
      live virus from tissue samples harvested at 28-100 days post-infection from
      convalescent pigs recovered from clinical or subclinical FMD. Despite lack of
      detection of infectious FMDV, there was a high prevalence of FMDV RNA detection
      in lymph nodes draining lesion sites harvested at 35 days post-infection, with
      the most frequent detection recorded in popliteal lymph nodes (positive detection
      in 88% of samples obtained from non-vaccinated pigs). Likewise, at 35 dpi, FMDV
      capsid antigen was localized within follicles of draining lymph nodes, but
      without concurrent detection of FMDV non-structural protein. There was a marked
      decline in the detection of FMDV RNA and antigen in tissue samples by 60 dpi, and
      no antigen or viral RNA could be detected in samples obtained at 100 dpi. The
      data presented herein provide the most extensive investigation of FMDV
      persistence in pigs. The overall conclusion is that domestic pigs are unlikely to
      be competent long-term carriers of infectious FMDV; however, transient
      persistence of FMDV protein and RNA in lymphoid tissues is common following
      clinical or subclinical infection. 

PMID- 24943475
TI  - Sex and age differences in the association of depression with obstructive
      coronary artery disease and adverse cardiovascular events.
AB  - BACKGROUND: Young women with coronary heart disease have high rates of depression
      and a higher risk of adverse events than men of similar age. Whether depression
      has a higher prognostic value in this group than in men and older women is not
      known. Our objective was to assess whether depression in young women is
      associated with higher risk of coronary artery disease (CAD) and adverse outcomes
      compared with similarly aged men and older women. METHODS AND RESULTS: We
      examined 3237 patients undergoing coronary angiography for evaluation of CAD and
      followed them for 2.9 years (median). Depressive symptoms were assessed with the
      Patient Health Questionnaire (PHQ)-9, and CAD burden was dichotomized based on
      its presence or absence. After multivariable adjustment for CAD risk factors,
      depressive symptoms predicted CAD presence in women aged <= 55 years (odds
      ratio=1.07 95% confidence interval [CI] 1.02 to 1.13 per 1 point increase in PHQ
      9 score), but not in men aged <= 55 years or women aged >55 years. Depressive
      symptoms also predicted increased risk of death in women aged <= 55 years
      (adjusted hazard ratio=1.07, 95% CI 1.02 to 1.14, per 1 point increase in PHQ-9
      score), but not in men aged <= 55 years and women aged >55 years, with P=0.02 for
      the depression-sex interaction and P=0.02 for depression-sex-age interaction.
      CONCLUSIONS: Among patients with suspected or established CAD, depressive
      symptoms are associated with increased risk of death, particularly in young
      women. This group may be especially vulnerable to the adverse cardiovascular
      effects of depression.

PMID- 24943479
TI  - Prognostic factors in patients with malignant pleural effusion.

PMID- 24943478
TI  - Infections of nervous necrosis virus in wild and cage-reared marine fish from
      South China Sea with unexpected wide host ranges.
AB  - The concerns about the impact of the nervous necrosis virus (NNV) infections in
      wild fish have been raised. This paper presents the results of quarterly surveys
      of NNV in wild and cage-reared marine fish from South China Sea. Samples of 892
      wild fish belonging to 69 species and 381 cage-reared fish belonging to 11
      species were collected and were detected by seminested PCR and nested PCR. In the
      case of seminested PCR, the positive signal was detected in 3.0% and 3.1% samples
      of wild and cage-reared fish, respectively. However, by nested RT-PCR, the
      positive signal was observed in 42.3% and 63.0% samples of wild and cage-reared
      fish, respectively. If the fish species were considered, the positive signal was
      detected in 21.7% and 72.7% species of wild and cage-reared fish by seminested
      PCR assay, respectively. However, by nested RT-PCR, the positive signal was
      observed in 65.2% and 100% species of wild and cage-reared fish, respectively.
      The nucleotide sequences of the nested PCR products were determined. Phylogenetic
      tree showed that all the obtained viral isolates belonged to the red-spotted
      grouper nervous necrosis virus (RGNNV) genotype. Thirty-five species of the
      marine fish were the new hosts of NNV. 

PMID- 24943480
TI  - Serotonergic reinforcement of intestinal barrier function is impaired in
      irritable bowel syndrome.
AB  - BACKGROUND: Alterations in serotonergic (5-HT) metabolism and/or intestinal
      integrity have been associated with irritable bowel syndrome (IBS). AIMS: To
      assess the effects of the precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on
      mucosal 5-HT availability and intestinal integrity, and to assess potential
      differences between healthy controls and IBS patients. METHODS: Fifteen IBS
      patients and 15 healthy volunteers participated in this randomised double-blind
      placebo-controlled study. Intestinal integrity was assessed by dual-sugar test
      and by determining the mucosal expression of tight junction proteins after
      ingestion of an oral bolus of 100 mg 5-HTP or placebo. Mucosal serotonergic
      metabolism was assessed in duodenal biopsy samples. RESULTS: 5-HTP administration
      significantly increased mucosal levels of 5-HIAA, the main metabolite of 5-HT, in
      both healthy controls (7.1 +/- 1.7 vs. 2.5 +/- 0.7 pmol/mg, 5-HTP vs. placebo, P
      = 0.02) and IBS patients (20.0 +/- 4.8 vs. 8.1 +/- 1.3 pmol/mg, 5-HTP vs.
      placebo, P = 0.02), with the latter group showing a significantly larger
      increase. Lactulose/L-rhamnose ratios were significantly lower after
      administration of 5-HTP (P < 0.05) in healthy controls and were accompanied by
      redistribution of zonula occludens-1 (ZO-1), pointing to reinforcement of the
      barrier. In IBS, expression of the tight junction proteins was significantly
      lower compared to healthy controls, and 5-HTP resulted in a further decrease in
      occludin expression. CONCLUSIONS: Oral 5-HTP induced alterations in mucosal 5-HT
      metabolism. In healthy controls, a reinforcement of the intestinal barrier was
      seen whereas such reaction was absent in IBS patients. This could indicate the
      presence of a serotonin-mediated mechanism aimed to reinforce intestinal barrier
      function, which seems to dysfunction in IBS patients.

PMID- 24943481
TI  - Fetal megacystis: experience of a single tertiary center in Switzerland over 20
      years.
AB  - OBJECTIVES: Megacystis (MC) is rare and often associated with other structural
      and chromosomal anomalies. In euploid cases with early oligohydramnios, prognosis
      is poor mainly due to pulmonary hypoplasia and renal damage. We report our
      experience of the past 20 years. METHODS: A retrospective review of cases with
      prenatally diagnosed MC was performed. Complete prenatal as well as postnatal
      medical records from 1989 to 2009 were reviewed focusing on diagnostic precision,
      fetal interventions [vesicocentesis (VC), vesicoamniotic shunt (VAS)], short- and
      long-term outcome, and potential prognostic factors. RESULTS: 68 cases were
      included. Follow-up was available in 54 cases (9 girls and 45 boys including 3
      cases with aneuploidy). We found 39 isolated MC at sonography (5 girls and 34
      boys). 24 fetuses with isolated MC underwent VC and VAS at 19.6 +/- 6.3 and 20 +/
      4.9 weeks of gestation, respectively. Survival rate was higher in male than in
      female fetuses (51 vs. 33%). Renal problems occurred in 4/14 prenatally treated
      fetuses and in 1/10 when cases with prune belly syndrome (PBS) were excluded from
      the analysis. CONCLUSIONS: Our study shows that a careful selection of cases with
      MC excluding fetuses with PBS and early treatment has still the potential to
      improve outcome.

PMID- 24943482
TI  - Therapeutic strategy for anastomotic biliary strictures after pediatric liver
      transplantation: two radically different approaches.

PMID- 24943483
TI  - Profiles of embryonic nuclear protein binding to the proximal promoter region of
      the soybean beta-conglycinin alpha subunit gene.
AB  - beta-Conglycinin, a major component of seed storage protein in soybean, comprises
      three subunits: alpha, alpha' and beta. The expression of genes for these
      subunits is strictly controlled during embryogenesis. The proximal promoter
      region up to 245 bp upstream of the transcription start site of the alpha subunit
      gene sufficiently confers spatial and temporal control of transcription in
      embryos. Here, the binding profile of nuclear proteins in the proximal promoter
      region of the alpha subunit gene was analysed. DNase I footprinting analysis
      indicated binding of proteins to the RY element and DNA regions including box I,
      a region conserved in cognate gene promoters. An electrophoretic mobility shift
      assay (EMSA) using different portions of box I as a probe revealed that multiple
      portions of box I bind to nuclear proteins. In addition, an EMSA using nuclear
      proteins extracted from embryos at different developmental stages indicated that
      the levels of major DNA-protein complexes on box I increased during embryo
      maturation. These results are consistent with the notion that box I is important
      for the transcriptional control of seed storage protein genes. Furthermore, the
      present data suggest that nuclear proteins bind to novel motifs in box I
      including 5'-TCAATT-3' rather than to predicted cis-regulatory elements. 

PMID- 24943484
TI  - Coffee: friend or foe for diabetes risk?

PMID- 24943486
TI  - Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association
      with Plasmodium falciparum infection among children in Iganga distric in Uganda.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme
      involved in the pentose phosphate pathway, its especially important in red blood
      cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked
      recessive hereditary disease characterised by abnormally low levels of G6PD.
      About 400 million people worldwide have a deficiency of this enzyme. The
      remarkable geographic correlation of G6PD deficiency distribution with historical
      endemicity patterns of malaria has led to suggestions that the two could be
      linked. Some studies have concluded that G6PD deficiency confers resistance to
      malaria. OBJECTIVE: To determine the prevalence of G6PD deficiency, and determine
      its relationship with prevalence and incidence of P. falciparum infection among
      children in Uganda. METHODS: This was longitudinal study involving 245 children,
      135 were actively followed up for 12 months. G6PD status was assessed for using
      PCR-RFLP method. A thick smear was done to determine presence of plasmodium
      trophozoites and parasite densities. RESULTS: A total of 245 children between 6
      months and 9 years were recruited. Of these 46.5% were males. Overall prevalence
      for the X-linked G6PD A- mutation was; 79.59% wild type, 12.65% heterozygous and
      7.76% homozygous or hemizygous. Among the males 14% were hemizygous. At baseline,
      40.8% had asymptomatic P falciparum infection. There was no statistically
      significant difference in prevalence and incidence rates of malaria infection
      among the different G6PD genotypes with prevalence among heterozygous,
      homozygous, and wild type being 29%, 42.6% and 43% respectively (p = 0.11) and
      incidence among heterozygous and wild type being 0.56 and 0.52 episodes/year (p =
      0.5). The heterozygous G6PD A- females had a lower parasite density compared to
      the wild type (2505 vs 941 parasites/MUL; P = 0.024). CONCLUSIONS: This study
      showed that 20.41% of the population in this part of Uganda carry the G6PD A
      mutation, within the range of 15-32% seen in other parts of Africa. P. falciparum
      infection incidence and prevalence rates are similar among the G6PD genotypes
      though, once infected, P. falciparum parasite densities are lowest among G6PD A-
      heterozygous females. This suggests differences in P. falciparum infection rates
      and severity of disease could be mediated by differences in parasite densities
      among the different G6PD genotypes.

PMID- 24943487
TI  - Human adipose tissue derived pericytes increase life span in Utrn (tm1Ked) Dmd
      (mdx) /J mice.
AB  - Duchenne muscular dystrophy (DMD) is still an untreatable lethal X-linked
      disorder, which affects 1 in 3500 male births. It is caused by the absence of
      muscle dystrophin due to mutations in the dystrophin gene. The potential
      regenerative capacity as well as immune privileged properties of mesenchymal Stem
      Cells (MSC) has been under investigation for many years in an attempt to treat
      DMD. One of the questions to be addressed is whether stem cells from distinct
      sources have comparable clinical effects when injected in murine or canine
      muscular dystrophy animal models. Many studies comparing different stem cells
      from various sources were reported but these cells were obtained from different
      donors and thus with different genetic backgrounds. Here we investigated whether
      human pericytes obtained from 4 different tissues (muscle, adipose tissue,
      fallopian tube and endometrium) from the same donor have a similar clinical
      impact when injected in double mutant Utrn (tm1Ked) Dmd (mdx) /J mice, a
      clinically relevant model for DMD. After a weekly regimen of intraperitoneal
      injections of 10(6) cells per 8 weeks we evaluated the motor ability as well as
      the life span of the treated mice as compared to controls. Our experiment showed
      that only adipose tissue derived pericytes are able to increase significantly (39
      days on average) the life span of affected mice. Microarray analysis showed an
      inhibition of the interferon pathway by adipose derived pericytes. Our results
      suggest that the clinical benefit associated with intraperitoneal injections of
      these adult stem cells is related to immune modulation rather than tissue
      regeneration.

PMID- 24943489
TI  - Population dynamics of Aceodromus convolvuli (Acari: Mesostigmata:
      Blattisociidae) on spontaneous plants associated with Jatropha curcas in central
      Brazil.
AB  - Spontaneously growing plants are commonly considered competitors of cultivated
      plants. Owing to the lack of specificity of many arthropods, spontaneous plants
      may be attacked by the same arthropods that attack cultivated plants and they may
      also harbor natural enemies of organisms harmful to cultivated plants. Aceodromus
      convolvuli Muma (Blattisociidae) has been reported recently in relatively large
      numbers in Tocantins state, central Brazil, mostly on Helicteres guazumifolia
      Kunth (Malvaceae). Very little has been reported about the population dynamics of
      blattisociid mites under field conditions. The objective of this work was to
      study the population dynamics of A. convolvuli in Gurupi, Tocantins state, to
      evaluate its possible interaction with associated mites. Monthly samples were
      taken from leaves of the 11 most abundant and frequent spontaneous plants in a
      Jatropha curcas L. (Euphorbiaceae) plantation. About 96.5 % of the specimens of
      A. convolvuli were collected in the rainy season. The patterns of variation of
      the population of A. convolvuli and of predators belonging to the family
      Phytoseiidae were similar, but A. convolvuli was much more numerous than all
      phytoseiid specimens combined. Highly significant correlations were observed
      between A. convolvuli densities and relative humidity or diversity of spontaneous
      plants. When only mites on H. guazumifolia were considered, highly significant
      correlation was also observed between densities of A. convolvuli and of mites of
      the family Tetranychidae. The results suggested that A. convolvuli could be a
      predator of tenuipalpid and/or tetranychid mites. Studies about its biology are
      needed to determine its preferred food sources and potential as biological
      control agent. 

PMID- 24943488
TI  - Contribution of mast cell-derived interleukin-1beta to uric acid crystal-induced
      acute arthritis in mice.
AB  - OBJECTIVE: Gouty arthritis is caused by the precipitation of monosodium urate
      monohydrate (MSU) crystals in the joints. While it has been reported that mast
      cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs
      during acute attacks of gout. This study was undertaken to assess the role of MCs
      in a mouse model of MSU crystal-induced acute arthritis. METHODS: We assessed the
      effects of intraarticular (IA) injection of MSU crystals in various strains of
      mice with constitutive or inducible MC deficiency or in mice lacking interleukin
      1beta (IL-1beta) or other elements of innate immunity. We also assessed the
      response to IA injection of MSU crystals in genetically MC-deficient mice after
      IA engraftment of wild-type or IL-1beta(-/-) bone marrow-derived cultured MCs.
      RESULTS: MCs were found to augment acute tissue swelling following IA injection
      of MSU crystals in mice. IL-1beta production by MCs contributed importantly to
      MSU crystal-induced tissue swelling, particularly during its early stages.
      Selective depletion of synovial MCs was able to diminish MSU crystal-induced
      acute inflammation in the joints. CONCLUSION: Our findings identify a previously
      unrecognized role of MCs and MC-derived IL-1beta in the early stages of MSU
      crystal-induced acute arthritis in mice.

PMID- 24943490
TI  - Geometric morphometric study of geographic and host-related variability in Aceria
      spp. (Acari: Eriophyoidea) inhabiting Cirsium spp. (Asteraceae).
AB  - The russet mite, Aceria anthocoptes (Nalepa), is the only eriophyoid that has
      been recorded on Cirsium arvense (L.) Scop. It has been noted in several European
      countries and recently in the USA. In this study we explored the geographic and
      host-related variability of Aceria spp. inhabiting different Cirsium spp. We
      applied landmark-based geometric morphometric methods to study morphological
      variability of three body regions (ventral, coxigenital and prodorsal) of 13
      Aceria spp. populations inhabiting five Cirsium spp. in Serbia (Europe) and four
      Cirsium spp. in Colorado (North America). Analyses of size and shape variation
      revealed statistically significant differences between Aceria spp. living on
      European native and North American native Cirsium spp., as well as between A.
      anthocoptes s.s. inhabiting European C. arvense and North American C. arvense.
      The coxigenital region was the most informative when considering inter-population
      shape differences. European Aceria spp. dwelling on Cirsium spp., including A.
      anthocoptes s.s. from C. arvense, are characterized by higher inter-population
      size and shape variability than their North American counterparts. This finding
      supports a Eurasian origin of A. anthocoptes, presumed to consist of a complex of
      cryptic taxa probably coevolved with host plants in the native environment.
      Morphological similarity among Aceria spp. inhabiting North American native
      Cirsium spp. may indicate that speciation of A. anthocoptes started relatively
      soon after the host shift to plants different from C. arvense in the invaded
      region. 

PMID- 24943491
TI  - Ligand chain length conveys thermochromism.
AB  - Thermochromic properties of a series of non-ionic copper compounds have been
      reported. Herein, we demonstrate that Cu(II) ion with straight-chain primary
      amine (A) and alpha-linolenic (fatty acid, AL) co-jointly exhibit thermochromic
      properties. In the current case, we determined that thermochromism becomes ligand
      chain length-dependent and at least one of the ligands (A or AL) must be long
      chain. Thermochromism is attributed to a balanced competition between the fatty
      acids and amines for the copper(II) centre. The structure-property relationship
      of the non-ionic copper compounds Cu(AL)2(A)2 has been substantiated by various
      physical measurements along with detailed theoretical studies based on time
      dependent density functional theory. It is presumed from our results that the
      compound would be a useful material for temperature-sensor applications.

PMID- 24943492
TI  - The Pseudomonas aeruginosa rhlG and rhlAB genes are inversely regulated and RhlG
      is not required for rhamnolipid synthesis.
AB  - BACKGROUND: Pseudomonas aeruginosa produces rhamnolipid biosurfactants involved
      in numerous phenomena including virulence. The transcriptional study of the rhlAB
      operon encoding two key enzymes for rhamnolipid synthesis led to the discovery of
      the quorum sensing system RhlRI. The latter positively controls the transcription
      of rhlAB, as well as of rhlC, which is required for di-rhamnolipid synthesis. The
      rhlG gene encodes an NADPH-dependent beta-ketoacyl reductase. Although it was
      reported to be required for the biosynthesis of the fatty acid part of
      rhamnolipids, its function in rhamnolipid synthesis was later questioned. The
      rhlG transcription and its role in rhamnolipid production were investigated here.
      RESULTS: Using 5'-RACE PCR, a luxCDABE-based transcriptional fusion, and
      quantitative reverse transcription-PCR, we confirmed two previously identified
      sigma70- and sigma54-dependent promoters and we identified a third promoter
      recognized by the extra-cytoplasmic function sigma factor AlgU. rhlG was
      inversely regulated compared to rhlAB and rhlC: the rhlG transcription was down
      regulated in response to N-butyryl-l-homoserine lactone, the communication
      molecule of the RhlRI system, and was induced by hyperosmotic stress in an AlgU
      dependent manner. Consistently with this transcriptional pattern, the single or
      double deletions of rhlG and PA3388, which forms an operon with rhlG, did not
      dramatically impair rhamnolipid synthesis. CONCLUSION: This first detailed study
      of rhlG transcription reveals a complex regulation involving three sigma factors
      and N-butyryl-l-homoserine lactone. We furthermore present evidences that RhlG
      does not play a key role in rhamnolipid synthesis.

PMID- 24943493
TI  - A critical review of HER2-positive gastric cancer evaluation and treatment: from
      trastuzumab, and beyond.
AB  - Identification of the importance of human epidermal growth factor receptor-2
      (HER2) status, biomarker testing and the development of anti-HER2 treatments have
      changed the prognosis of breast and gastric cancers. The addition of trastuzumab
      to chemotherapy has improved outcomes for patients with HER2-positive metastatic
      adenocarcinoma of the stomach and gastroesophageal junction, but some relevant
      issues remain to be elucidated or will emerge with new drugs. This article
      reviews the current state of HER2 in gastric cancer focusing on diagnostic and
      anti-HER2 targeted treatment issues and the role of trastuzumab in localized
      disease, and its combination or integration with new therapies.

PMID- 24943494
TI  - An approach to sequential NMR assignments of proteins: application to chemical
      shift restraint-based structure prediction.
AB  - A procedure for the simultaneous acquisition of {HNCOCANH & HCCCONH} chemical
      shift correlation spectra employing sequential [Formula: see text] data
      acquisition for moderately sized proteins is presented. The suitability of the
      approach for obtaining sequential resonance assignments, including complete
      [Formula: see text] and [Formula: see text] chemical shift information, is
      demonstrated experimentally for a [Formula: see text] and [Formula: see text]
      labelled sample of the C-terminal winged helix (WH) domain of the minichromosome
      maintenance (MCM) complex of Sulfolobus solfataricus. The chemical shift
      information obtained was used to calculate the global fold of this winged helix
      domain via CS-Rosetta. This demonstrates that our procedure provides a reliable
      and straight-forward protocol for a quick global fold determination of moderately
      sized proteins. 

PMID- 24943495
TI  - A systematic review to establish health-related quality-of-life domains for
      intervention targets in cancer cachexia.
AB  - OBJECTIVES: To develop a model of the impact of cancer cachexia on patients by
      identifying the relevant health-related quality-of-life (HRQOL) issues, and to
      use the model to identify opportunities for intervention. METHODS: Standard
      systematic review methods were followed to identify papers which included direct
      quotes from cancer patients with cachexia or problems with eating or weight loss.
      Following thematic synthesis methodology, the quotes were coded, and themes and
      metathemes were extracted. The metathemes were used to develop a model of the
      patient's experience of cachexia. RESULTS: 18 relevant papers were identified
      which, in total, contained interviews with more than 250 patients. 226 patient
      quotes were extracted from the papers and 171 codes. 26 themes and 8 metathemes
      were formulated. The model developed from the metathemes demonstrated a direct
      link between eating and food problems and negative emotions and also a link
      mediated by the associated physical decline. These links provide opportunities
      for interventions. CONCLUSIONS: There are a vast number of HRQOL issues
      associated with cancer cachexia as identified from patients' own words. The model
      generated from these issues indicates that relationships, coping and knowledge of
      the condition are important components of new psychosocial interventions.

PMID- 24943496
TI  - How reliable are data for the ecotoxicity of trivalent chromium to Daphnia magna?
AB  - Risk assessments from the European Union and the World Health Organization report
      values for acute and chronic toxicity of Cr(III) to Daphnia magna in the range of
      0.6 mg/L to 111 mg/L and 0.047 mg/L to 3.4 mg/L, respectively. To understand
      whether factors other than the use of different test media and data reporting
      contribute to this variability, the authors tested the acute (48-h) and chronic
      (21-d) toxicities of Cr(III) to D. magna according to Organisation for Economic
      Co-operation and Development (OECD) methods. Filterable (0.45-um) chromium
      concentrations were measured at 0 h, 6 h, 24 h, and 48 h, the latter value
      corresponding to the total duration of the acute tests and to the interval
      between medium renewals in chronic tests. In highly alkaline media (4.9 meq/L),
      Cr concentrations decreased rapidly below the analytical detection limit, and no
      toxicity was observed. In less alkaline media (approximately 0.8 meq/L), the
      decrease in filterable Cr concentrations was inversely proportional to the
      quantity of added Cr(III). The authors concluded that existing data likely
      underestimate the ecotoxicity of Cr(III) to D. magna. A reliable assessment of
      the hazard of Cr(III) to D. magna must consider that exposure concentrations can
      decrease markedly from the beginning to the end of a test and that medium
      alkalinity strongly influences the outcome of laboratory toxicity tests.

PMID- 24943497
TI  - Common garden comparison of the leaf-out phenology of woody species from
      different native climates, combined with herbarium records, forecasts long-term
      change.
AB  - A well-timed phenology is essential for plant growth and reproduction, but
      species-specific phenological strategies are still poorly understood. Here, we
      use a common garden approach to compare biannual leaf-out data for 495 woody
      species growing outdoors in Munich, 90% of them not native to that climate
      regime. For three species, data were augmented by herbarium dates for 140-year
      long time series. We further meta-analysed 107 temperate-zone woody species in
      which leaf-out cues have been studied, half of them also monitored here. Southern
      climate-adapted species flushed significantly later than natives, and photoperiod
      and chilling- sensitive species all flushed late. The herbarium method revealed
      the extent of species-specific climate tracking. Our results forecast that: (1) a
      northward expansion of southern species due to climate warming will increase the
      number of late flushers in the north, counteracting documented and expected
      flushing time advances; and (2) photoperiod- and chilling-sensitive woody species
      cannot rapidly track climate warming. 

PMID- 24943498
TI  - Mammography reduces risk of breast cancer death by 28%, study finds.

PMID- 24943501
TI  - Central giant cell granuloma in pediatric maxilla: surgical management.
AB  - Central giant cell granuloma (CGCG) is an intraosseous lesion consisting of
      fibrous cellular tissue that contains multiple foci of hemorrhage, multinucleated
      giant cells, and occasional trabeculae of woven bone. An 8-year-old boy presented
      himself complaining of a painless swelling in the left maxilla that had started 1
      year. Computed tomography (CT) scan confirmed a poorly defined multilocular
      radiolucent lesion in the left maxilla crossing the midline. The patient
      underwent enucleation through an intraoral approach of the lesion. The biopsy
      revealed multinucleated giant cells in a fibrous stroma. A CT was taken
      approximately 1 year postoperatively. There was no clinical or radiographic
      evidence of recurrence. Therefore, surgical treatment of CGCG can be performed,
      trying to preserve the surrounding anatomic structures, which can be maintained
      in case the lesion does not show an aggressive clinical behavior, avoiding large
      surgical defects which are undesirable in children. 

PMID- 24943500
TI  - Deep brain stimulation of the prelimbic medial prefrontal cortex: quantification
      of the effect on glucose metabolism in the rat brain using [(18) F]FDG microPET.
AB  - PURPOSE: Prefrontal cortex (PFC) deep brain stimulation (DBS) has been proposed
      as a therapy for addiction and depression. This study investigates changes in rat
      cerebral glucose metabolism induced by different DBS frequencies using MUPET.
      PROCEDURES: One hour DBS of the prelimbic area (PL) of the medial PFC (mPFC) (60
      Hz, 130 Hz or sham) in rats (n = 9) was followed by 2-deoxy-2-[(18) F] fluoro-D
      glucose ([(18) F]FDG) MUPET. RESULTS: Sixty Hz DBS elicited significant
      hypermetabolism in the ipsilateral PL ([(18) F]FDG uptake +5.2 +/- 2.3 %, p <
      0.05). At 130 Hz, hypometabolism was induced in the ipsilateral PL (-2.5 +/- 2.6
      %, non-significant). Statistical parametric mapping revealed hypo and
      hypermetabolism clusters for both 60 and 130 Hz versus sham and show a certain
      state of alertness (increased activity in sensory and motor-related regions)
      mainly for 60 Hz. CONCLUSIONS: This study suggests the potential of 60 Hz PL mPFC
      DBS for the treatment of disorders associated with prefrontal hypofunction.

PMID- 24943503
TI  - Intracerebral arachnoid cyst treated with ommaya reservoir implantation in a
      patient younger than two years.
AB  - Intracranial arachnoid cysts are rare cystic-appearing intracranial masses. In
      rarer cases, the arachnoid cysts originate from brain parenchyma, which is
      defined as intracerebral arachnoid cyst. Here, we present a patient younger than
      2 years with massive intracranial arachnoid cysts (one of which was intracerebral
      arachnoid cyst), whose clinical symptoms included megacephaly and limb weakness.
      Ommaya reservoir implantation and repeated aspiration of the intracerebral cyst
      fluid were performed. The symptoms gradually improved, and the intracerebral
      arachnoid cyst gradually disappeared during 13 months of follow-up. The case
      highlights the potential of Ommaya reservoir implantation in the treatment of
      intracerebral arachnoid cyst, especially for young patients. We also reviewed the
      published literatures concerning the rare condition, including the mechanisms for
      its pathogenesis and enlargement. 

PMID- 24943499
TI  - Accumulation of trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in
      prostate cancer due to androgen-induced expression of amino acid transporters.
AB  - PURPOSE: Androgens play a crucial role in prostate cancer progression, and trans
      1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18) F]FACBC) are used
      for visualization of prostate cancer. We examined the effect of androgen on the
      expression of amino acid transporters related to anti-[(18)F]FACBC transport and
      uptake of trans-1-amino-3-fluoro-[1-(14)C]cyclobutanecarboxylic acid (anti
      [(14)C]FACBC). PROCEDURES: Expression of amino acid transporters and uptake of
      anti-[(14)C]FACBC in androgen receptor (AR)-positive LNCaP and AR-negative DU145
      human prostate cancer cells cultured with/without 5alpha-dihydrotestosterone
      (DHT) and the effect of bicalutamide, an AR antagonist, on DHT-associated changes
      were investigated. RESULTS: DHT stimulated the expression of amino acid
      transporters ASCT2, SNAT5, 4F2 heavy chain, and LAT3 in LNCaP but not in DU145
      cells. Anti-[(14)C]FACBC uptake was enhanced, in a DHT-dependent manner, in LNCaP
      cells only. CONCLUSIONS: DHT enhanced the expression of ASCT2, the transporter
      responsible for anti-[(18)F]FACBC uptake, thereby increasing anti-[(14)C]FACBC
      uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to
      the distinct anti-[(18)F]FACBC accumulation pattern in prostate cancer.

PMID- 24943502
TI  - Differentiated adipose-derived stem cell cocultures for bone regeneration in
      polymer scaffolds in vivo.
AB  - Critical-sized bone defects can lead to significant morbidity, and interventions
      are limited by the availability and donor-site morbidity of bone grafts. Polymer
      scaffolds seeded with cells have been explored to replace bone grafts. Adipose
      derived stem cells have shown great promise for vascularization and osteogenesis
      of these constructs, and cocultures of differentiated stem cells are being
      explored to augment vessel and bone formation. Adipose-derived stem cells were
      differentiated into endothelial cells and osteoblasts, and in vitro studies
      showed increased proliferation of cocultured cells compared with undifferentiated
      adipose-derived stem cells and monocultures of endothelial cells and osteoblasts.
      The cells were seeded into polylactic acid gas-plasma-treated scaffolds as
      cocultures and monocultures and then implanted into critical-sized rat calvarial
      defects. The cocultures were in a 1:1 osteoblast to endothelial cell ratio. The
      increase in proliferation seen by the cocultured cells in vitro did not translate
      to increased vascularization and osteogenesis in vivo. In vivo, there were trends
      of increased vascularization in the endothelial cell group and increased
      osteogenesis in the osteoblast and endothelial monoculture groups, but no
      increase was seen in the coculture group compared with the undifferentiated
      adipose-derived stem cells. Endothelial cells enhance vascularization and
      osteoblast and endothelial cell monocultures enhance bone formation in the
      polymer scaffold. Predifferentiation of adipose-derived stem cells is promising
      for improving vascularization and osteogenesis in polymer scaffolds but requires
      future evaluation of coculture ratios to fully characterize this response.

PMID- 24943504
TI  - Hypoglossal paralysis after intubation for nasal surgery.

PMID- 24943505
TI  - Intracranial pseudoaneurysm associated with orbitozygomatic complex fracture.
AB  - Fractures of the orbitozygomatic complex are one of the most common facial
      fractures encountered by plastic surgeons. Many would consider this to be
      primarily a cosmetic deformity; however, these injuries can be associated with
      acute life-threatening complications. Intracranial pseudoaneurysm, although rare,
      is a well-documented complication of blunt facial trauma, which most plastic
      surgeons are unaware of. We present the case of a 20-year-old woman who developed
      an intracranial pseudoaneurysm after blunt facial trauma to illustrate the
      importance of (1) understanding this rare but highly morbid complication, (2)
      assessing high-risk patients for pseudoaneurysm, and (3) delaying reconstruction
      in high-risk patients. 

PMID- 24943506
TI  - The selective odontoidectomy: endoscopic endonasal approach to the craniocervical
      junction.
AB  - OBJECTIVE: The resection of the odontoid process via an extended endoscopic
      endonasal approach has been recently proposed as an alternative to the
      microscopic transoral method. We aimed to delineate a minimally invasive
      endoscopic transnasal odontoidectomy and to describe the endoscopic anatomy of
      the anterior craniovertebral junction (CVJ). MATERIALS AND METHODS: The anterior
      CVJ of 14 fresh adult cadavers were selectively accessed via a binostril
      endoscopic endonasal approach using 0- and 30-degree endoscopes. RESULTS: The
      nasopharynx was widely exposed without removing any of the turbinates and without
      performing a sphenoidotomy. Occipital condyles and lateral masses of the C1
      vertebra have been exposed inferiorly at lateral margins of the exposure, in
      addition to the foramen lacerum, which came into view at the superolateral corner
      of the operative field. The anterior arch of C1 and the upper 1.5 cm of the
      odontoid process of C2 have been removed via a minimally invasive endoscopic
      transnasal approach in all dissections. CONCLUSIONS: We propose the selective
      odontoidectomy as a minimally invasive method for the endoscopic endonasal
      removal of the odontoid process. By using this approach, turbinates and the
      sphenoid sinus remain unharmed. In addition, this approach may be used in
      exposing pathologies situated laterally at the anterior CVJ, such as the lateral
      masses of atlas and occipital condyles.

PMID- 24943507
TI  - Inflammatory pseudotumor of the infratemporal fossa leading to orbital apex
      syndrome.
AB  - An inflammatory pseudotumor is a rare benign disease presenting with non-specific
      chronic inflammation, and reported occurrences involving the skull base are
      relatively rare. A 65-year-old man became aware of pain around the right
      temporomandibular joint and mild trismus, and palsies of the cranial nerves III,
      IV, V, and VI were observed. A biopsy was performed under general anesthesia with
      an infratemporal fossa approach, and he was diagnosed with inflammatory
      pseudotumor of the infratemporal fossa. There was a rapid improvement in symptoms
      after the start of steroid administration, and 29 months after the initial
      consultation, the patient remained under strict observation. The 3 criteria in
      our department for confirming progression of the disease are (1) clinical
      symptoms, (2) C-reactive protein levels in blood tests, and (3) contrast effect
      of the tumor on magnetic resonance imaging. This is a rare case report to
      demonstrate the inflammatory pseudotumor of the infratemporal fossa leading to
      orbital apex syndrome. 

PMID- 24943508
TI  - Primary ciliary dyskinesia: overlooked and undertreated in children.
AB  - Primary ciliary dyskinesia (PCD) is a multi-organ disorder associated with
      chronic oto-sino-pulmonary disease, neonatal respiratory distress, situs
      abnormalities and reduced fertility. Repeated respiratory tract infections leads
      to the almost universal development of bronchiectasis. These clinical
      manifestations are a consequence of poorly functioning motile cilia. However,
      confirming the diagnosis is quite difficult and is often delayed, so the true
      incidence of PCD may be significantly higher than current estimates. Nasal nitric
      oxide has been earmarked as a useful screening tool for identifying patients, but
      its use is limited in pre-school-aged children. Due to the rarity of PCD, the
      evidence base for management is somewhat limited, and treatment regimens are
      extrapolated from other suppurative lung disorders, like cystic fibrosis. 

PMID- 24943509
TI  - Creating new evolutionary pathways through bioinvasion: the population genetics
      of brushtail possums in New Zealand.
AB  - Rapid increases in global trade and human movement have created novel mixtures of
      organisms bringing with them the potential to rapidly accelerate the evolution of
      new forms. The common brushtail possum (Trichosurus vulpecula), introduced into
      New Zealand from Australia in the 19th century, is one such species having been
      sourced from multiple populations in its native range. Here, we combine
      microsatellite DNA- and GIS-based spatial data to show that T. vulpecula
      originating from at least two different Australian locations exhibit a population
      structure that is commensurate with their introduction history and which cannot
      be explained by landscape features alone. Most importantly, we identify a hybrid
      zone between the two subspecies which appears to function as a barrier to
      dispersal. When combined with previous genetic, morphological and captive
      studies, our data suggest that assortative mating between the two subspecies may
      operate at a behavioural or species recognition level rather than through
      fertilization, genetic incompatibility or developmental inhibition. Nevertheless,
      hybridization between the two subspecies of possum clearly occurs, creating the
      opportunity for novel genetic combinations that would not occur in their natural
      ranges and which is especially likely given that multiple contact zones occur in
      New Zealand. This discovery has implications for wildlife management in New
      Zealand because multiple contact zones are likely to influence the dispersal
      patterns of possums and because differential susceptibility to baiting with
      sodium fluoroacetate between possums of different origins may promote novel
      genetic forms. 

PMID- 24943511
TI  - The relationship between interfacial bonding and radiation damage in adsorbed
      DNA.
AB  - We have performed a comparison of the radiation damage occurring in DNA adsorbed
      on gold in two different configurations, when the DNA is thiolated and bound
      covalently to the substrate and when it is unthiolated and interacts with the
      substrate through the bases. Both molecules were found to organize so as to
      protrude from the surface at ~45 degrees. Changes in the time-dependent C 1s and
      O 1s X-ray photoelectron (XP) spectra resulting from irradiation were interpreted
      to arise from cleavage of the phosphodiester bond and possibly COH desorption. By
      fitting the time-dependent XP spectra to a simple kinetic model, time constants
      were extracted, which were converted to cross sections and quantum yields for the
      damage reaction. The radiation induced damage is significantly higher for the
      thiolated DNA. N 1s X-ray absorption spectrum revealed the N-C=N LUMO is more
      populated in the unthiolated molecule, which is due to a higher degree of charge
      transfer from the substrate to this LUMO in the unthiolated case. Since the N-C=N
      LUMO of the thiolated molecule is comparatively less populated, it is more
      effective in capturing low energy electrons resulting in a higher degree of
      damage.

PMID- 24943512
TI  - Monitoring tectonic uplift and paleoenvironmental reconstruction for marine
      terraces near Magaracik and Samandag, Hatay Province, Turkey.
AB  - Near Hatay, the Antakya-Samandag-Cyprus Fault (ASCF), East Anatolian and Dead Sea
      Fault Zones, the large faults that form the edges of the African, Anatolian,
      Cyprus and Arabian Plates, all produce large earthquakes, which have decimated
      Hatay repeatedly. Near Samandag, Hatay, differential vertical displacement on the
      ASCF has uplifted the southeastern side relative to northwestern side, producing
      large fault scarps that parallel the Asi (Orontes) River. Tectonic uplift coupled
      with Quaternary sealevel fluctuations has produced several stacked marine
      terraces stranded above current sealevel. This study dated 24 mollusc samples
      from 10 outcrops on six marine terraces near Samandag electron spin resonance
      (ESR). Ages were calculated using time-averaged and volumetrically averaged
      external dose rates, modelled by assuming typical water depths for the individual
      species and sediment thicknesses estimated from geological criteria. Uplift rates
      were then calculated for each fault block. At all the Magaracik terraces, the
      dates suggest that many shells were likely reworked. On the 30 m terrace at
      Magaracik IV (UTM 766588-3999880), Lithophagus burrows with in situ shells cross
      the unconformity. One such shell dated to 62 +/- 6 ka, setting the minimum
      possible age for the terrace. For all the Magaracik terraces at ~30 m above mean
      sealevel (amsl), the youngest ages for the reworked shells, which averaged 60 +/-
      3 ka for six separate analyses, sets the maximum possible age for this unit.
      Thus, the terrace must date to 60-62 +/- 3 ka, at the MIS 3/4 boundary when
      temperatures and sealevels were fluctuating rapidly. Older units dating to MIS 7,
      6, and 5 likely were being eroded to supply some fossils found in this terrace.
      At Magaracik Dump (UTM 765391-4001048), ~103 m amsl, Ostrea and other shells were
      found cemented in growth position to the limestone boulders outcropping there
      <2.0 m above a wave-eroded notch. If the oysters grew at the same time as the
      wave-cut notch and the related terrace, the date, 91 +/- 13 ka, for the oysters,
      this fault block has been uplifted at 1.19 +/- 0.15 m ky(-1), since MIS 5c. At
      Samandag Kurt Stream at 38 m amsl, molluscs were deposited fine sandy gravel,
      which was likely formed in a large tidal channel. Four molluscs averaged 116 +/-
      5 ka. If these molluscs have not been reworked, this fault block has uplifted at
      0.34 +/- 0.05 m ky(-1) since the MIS 5d/5e boundary. The differences in these
      uplift rates suggests that at least one, and possibly two, hitherto undiscovered
      faults may separate the Magaracik Dump site from the other Magaracik sites and
      from the Samandag Kurt Stream site. 

PMID- 24943510
TI  - Interleukin-4 up-regulation of epidermal interleukin-19 expression in
      keratinocytes involves the binding of signal transducer and activator of
      transcription 6 (Stat6) to the imperfect Stat6 sites.
AB  - Interleukin-19 (IL-19) plays an important role in asthma by stimulating T helper
      type 2 (Th2) cytokine production. Interestingly, IL-4, a key Th2 cytokine, in
      turn up-regulates IL-19 expression in bronchial epithelial cells, so forming a
      positive feedback loop. In atopic dermatitis (AD), another Th2 disease closely
      related to asthma, IL-19 is up-regulated in the skin. We propose to use IL-4
      transgenic (Tg) mice and human keratinocyte culture to delineate the molecular
      mechanisms involved in the up-regulation of IL-19 in AD. IL-19 is similarly up
      regulated in the skin of IL-4 Tg mice as in human AD. Next we show that IL-4 up
      regulates IL-19 expression in keratinocytes. Interestingly, the up-regulation was
      suppressed by a pan-Janus kinase (Jak) inhibitor, suggesting that the Jak-signal
      transducer and activator of transcription (Jak-STAT) pathway may be involved.
      Dominant negative studies further indicate that STAT6, but not other STATs,
      mediates the up-regulation. Serial 5' deletion of the IL-19 promoter and
      mutagenesis studies demonstrate that IL-4 up-regulation of IL-19 in keratinocytes
      involves two imperfect STAT6 response elements. Finally, chromatin
      immunoprecipitation assay studies indicate that IL-4 increases the binding of
      STAT6 to its response elements in the IL-19 promoter. Taken together, we
      delineate the detailed molecular pathway for IL-4 up-regulation of IL-19 in
      keratinocytes, which may play an important role in AD pathogenesis. 

PMID- 24943513
TI  - Introducing PeptoPlexes: polylysine-block-polysarcosine based polyplexes for
      transfection of HEK 293T cells.
AB  - A series of well-defined polypeptide-polypeptoid block copolymers based on the
      body's own amino acids sarcosine and lysine are prepared by ring opening
      polymerization of N-carboxyanhydrides. Block lengths were varied between 200-300
      for the shielding polysarcosine block and 20-70 for the complexing polylysine
      block. Dispersity indexes ranged from 1.05 to 1.18. Polylysine is polymerized
      with benzyloxycarbonyl as well as trifluoroacetyl protecting groups at the
      epsilon-amine group and optimized deprotection protocols for both groups are
      reported. The obtained block ionomers are used to complex pDNA resulting in the
      formation of polyplexes (PeptoPlexes). The PeptoPlexes can be successfully
      applied in the transfection of HEK 293T cells and are able to transfect up to 50%
      of cells in vitro (FACS assay), while causing no detectable toxicity in an
      Annexin V assay. These findings are a first indication that PeptoPlexes may be a
      suitable alternative to PEG based non-viral transfection systems. 

PMID- 24943514
TI  - Molecular identification of the chitinase genes in Plasmodium relictum.
AB  - BACKGROUND: Malaria parasites need to synthesize chitinase in order to go through
      the peritrophic membrane, which is created around the mosquito midgut, to
      complete its life cycle. In mammalian malaria species, the chitinase gene
      comprises either a large or a short copy. In the avian malaria parasites
      Plasmodium gallinaceum both copies are present, suggesting that a gene
      duplication in the ancestor to these extant species preceded the loss of either
      the long or the short copy in Plasmodium parasites of mammals. Plasmodium
      gallinaceum is not the most widespread and harmful parasite of birds. This study
      is the first to search for and identify the chitinase gene in one of the most
      prevalent avian malaria parasites, Plasmodium relictum. METHODS: Both copies of
      P. gallinaceum chitinase were used as reference sequences for primer design.
      Different sequences of Plasmodium spp. were used to build the phylogenetic tree
      of chitinase gene. RESULTS: The gene encoding for chitinase was identified in
      isolates of two mitochondrial lineages of P. relictum (SGS1 and GRW4). The
      chitinase found in these two lineages consists both of the long (PrCHT1) and the
      short (PrCHT2) copy. The genetic differences found in the long copy of the
      chitinase gene between SGS1 and GRW4 were higher than the difference observed for
      the cytochrome b gene. CONCLUSION: The identification of both copies in P.
      relictum sheds light on the phylogenetic relationship of the chitinase gene in
      the genus Plasmodium. Due to its high variability, the chitinase gene could be
      used to study the genetic population structure in isolates from different host
      species and geographic regions.

PMID- 24943515
TI  - Liability versus innovation: the legal case for regenerative medicine.
AB  - Medical innovation occupies a position somewhere between standard practice and
      clinical research, but innovation is primarily intended to benefit an individual
      patient where standard treatment fails. Medical innovations in the area of
      regenerative medicine have the potential to completely transform medical
      practice, but rely upon some major revision to the nature of treatments beyond
      drug-based therapies. There is considerable investment in scientific and clinical
      research, but further attention could be paid to legal barriers to medical
      innovation imposed by the threat of medical malpractice. We survey in this
      article the legal framework for making determinations of medical malpractice in
      general, and highlight the issues specific to innovative treatments. In essence,
      liability could be imposed for failing to adequately inform the patient about the
      innovative nature of the suggested therapy or based on the fact that the risks
      outweighed the benefits. As for the latter, we examine whether liability is
      likely to be based merely on deviating from existing practice or on an
      examination on the merits of the treatments' risks and benefits. The facts that
      some risks are unforeseeable and some benefits are external to the patient
      complicate negligence determinations. The first fact relates to the problem of
      judging adverse events in hindsight; the second, to the obligation to make
      decisions based on the patient's best interest and avoid conflict of interests.
      In addition, we evaluate the relationship between the obligations to secure the
      patient's informed consent and to avoid clinical negligence. We identify the need
      for further research to examine the significance of the putative anti-innovation
      bias that current liability regimen has, and to examine whether a move to strict
      liability might avoid such bias, while being fair to patients who contribute for
      the advancement of medical knowledge by participating in innovative therapies. 

PMID- 24943516
TI  - Antithrombin and mortality in severe pneumonia patients with sepsis-associated
      disseminated intravascular coagulation: an observational nationwide study.
AB  - BACKGROUND: The association between antithrombin use and mortality in patients
      with sepsis-associated disseminated intravascular coagulation (DIC) remains
      controversial. OBJECTIVES: To examine the hypothesis that antithrombin could be
      effective in the treatment of patients with sepsis-associated DIC following
      severe pneumonia. METHODS: Propensity score and instrumental variable analyses
      were performed by use of a nationwide administrative database, the Japanese
      Diagnosis Procedure Combination inpatient database. The main outcome was 28-day
      mortality. RESULTS: Severe pneumonia patients diagnosed with sepsis-associated
      DIC (n = 9075) were categorized into antithrombin (n = 2663) and control (n =
      6412) groups. Propensity score matching created a matched cohort of 2194 pairs of
      patients with and without antithrombin use. Mortality differences were found
      between the two groups (antithrombin vs. control: unmatched, 40.8% vs. 45.7%;
      propensity-matched, 40.6% vs. 44.2%; inverse probability-weighted, 41.1% vs.
      45.1%). Multiple logistic regression analyses showed an association between
      antithrombin use and 28-day mortality (unmatched with propensity score adjusted,
      adjusted odds ratio [OR] 0.87, 95% confidence interval [CI] 0.78-0.97; propensity
      matched, adjusted OR 0.85, 95% CI 0.75-0.97; inverse probability-weighted,
      adjusted OR 0.85, 95% CI 0.79-0.90). An analysis with the hospital antithrombin
      prescribing rate as an instrumental variable showed that receipt of antithrombin
      was associated with a 9.9% (95% CI 3.5-16.3) reduction in 28-day mortality.
      CONCLUSIONS: This retrospective, large, nationwide database study demonstrates
      that antithrombin administration may be associated with reduced 28-day mortality
      in patients with severe pneumonia and sepsis-associated DIC. A large,
      multinational randomized trial is required.

PMID- 24943517
TI  - The impact of antihyperlipidemic drugs on the viral load of patients with chronic
      hepatitis C infection: a meta-analysis.
AB  - Several studies investigating the role of statins and fibrates in chronic
      hepatitis C virus (HCV) infection offered so far conflicting evidence regarding
      the antiviral potency of these medications, whereas combination of these drugs
      with pegylated interferon and ribavirin improved in some trials therapeutic
      outcome. We conducted a literature search to identify trials that included
      monoinfected HCV patients, treated with statins or fibrates as monotherapy with
      the primary end point of our meta-analysis being the quantitative change of HCV
      RNA induced by these medications. Logarithmic changes of the viral load
      (DeltalogVL) and confidence intervals (CIs) were calculated according to the
      DerSimonian-Laird estimate. Statistical heterogeneity was assessed with the I2
      statistic. We identified eight observational studies that evaluated the potency
      of bezafibrate and different statins as monotherapy to induce a significant
      reduction of HCV-RNA in HCV-monoinfected patients (n = 281). Overall, a
      significant reduction of viral load with mean 0.19 [log10 IU/mL] (95%-confidence
      interval, (CI) 0.11-0.28) could be observed when antihyperlipidemic medications
      were administered. Bezafibrate featured the highest antiviral efficacy (0.45
      log10 reduction, 95%-CI, 0.17-0.72) among all medications and fluvastatin (0.20
      log10 reduction, 95%-CI, 0.09-0.31) among all statins tested. Based on meta
      analysis, fibrates and statins induce a reduction of HCV viral load. We suggest
      that the addition of statins and fibrates to antiviral regimes, especially in HCV
      patients with concomitant dyslipidemia, could beside the established reduction of
      cardiovascular risk increase the potency of antiviral therapy.

PMID- 24943518
TI  - Elderly people's interaction with advanced technology.
AB  - Aging of population is an inevitable process by which the number of elderly
      people is increasing. Rapid development of information and communication
      technology (ICT) is changing basic needs of elderly people; therefore society
      should ensure opportunities for elderly to learn and use ICT in a way to manage
      their daily life activities and in this way enable them participation in the
      information and knowledge society. The purpose of the study was to find out
      whether elderly are acquainted with the advanced technology and to what extent
      they use it or they desire to use it. Within the single point study we
      interviewed 100 randomly selected elderly people from different geographical
      regions in Slovenia. Results showed the differences in the use of advanced
      technology by Slovenian regions; therefore in the future activities should be
      focused on organizing promotional and demonstrational activities including ICT
      courses to increase elderly's motivation for ICT interaction. 

PMID- 24943519
TI  - Promoting the meaningful use of health information for New Zealand consumers.
AB  - A cornerstone of 'meaningful use' of health information is engaging consumers and
      their families. Yet for consumers to be engaged requires an informed population
      and therefore focus on consumer's health information needs. Reports indicated
      consumers want health information, yet little was known about their internet use
      or perception of electronic health information. This New Zealand study surveyed
      consumers to gain an understanding of their health information requirements. Some
      1783 questionnaires were available for descriptive statistical analyses. The
      internet was the third most preferred source of health information. Two thirds of
      participants had used the internet to access health information, because of the
      speed of access and to find information before going to the doctor. There was
      little awareness or use of existing New Zealand-based online health resources.
      Study implications include promoting existing resources and increasing the use of
      electronic communication between consumers and healthcare providers as these are
      currently underutilized. 

PMID- 24943520
TI  - Comparison of consumer derived evidence with an omaha system evidence-based
      practice guideline for community dwelling older adults.
AB  - Consumer involvement in healthcare is critical to support continuity of care for
      consumers to manage their health while transitioning from one care setting to
      another. Validation of evidence-based practice (EBP) guideline by consumers is
      essential to achieving consumer health goals over time that is consistent with
      their needs and preferences. The purpose of this study was to compare an Omaha
      System EBP guideline for community dwelling older adults with consumer-derived
      evidence of their ongoing needs, resources, and strategies after home care
      discharge. All identified problems were relevant for all patients except for
      Neglect and Substance use. Ten additional problems were identified from the
      interviews, five of which affected at least 10% of the participants. Consumer
      derived evidence both validated and expanded EBP guidelines; thus further
      emphasizing the importance of consumer involvement in the delivery of home
      healthcare. 

PMID- 24943521
TI  - Toward a typology of technology users: how older people experience technology's
      potential for active aging.
AB  - This paper outlines an emerging typology of older users of information and
      communication technology (ICT) to facilitate active aging. Through inductive data
      analysis from focus groups, iterative workshops, and personal interviews, we
      suggest three types of technology users. These types are "the Excluded," "the
      Entertained," and "the Networker." Clearly, ICT offers several benefits to those
      who are enthusiastic and frequent users, exemplified as the Entertained and the
      Networker. Hence, our findings support the notion of technology as a tool to
      maintain or increase an older person's engagement and activity level. Conversely,
      for those reluctant, uninterested, or incapable of using ICT, such potentials are
      limited and imply fewer opportunities for participation in activities. 

PMID- 24943522
TI  - Attitudes of student nurses enrolled in e-learning course towards academic
      dishonesty: a descriptive-exploratory study.
AB  - The author investigated attitudes of nursing students enrolled in e-Learning
      towards academic dishonesty. The descriptive-exploratory design was used in the
      conduct of the study. Respondents were randomly selected 36 junior and senior
      nursing students. It revealed that nursing students perceived as neutral (mean =
      2.77, mean = 3.17) in taking responsibility for promoting academic integrity in e
      learning. The paraphrasing a sentence from internet source without referencing it
      (38.89%) got the most form of cheating. Female and level four (4) nursing
      students revealed as the most cheaters. The reasons not to cheat, nursing
      students considered punishment, and education or learning (91.67%) got the
      highest in ranks, and simply wrong (75%) got the lowest rank. Hence, there is a
      need to look on how to maintain academic honesty among nursing students in and
      out of the university with respect to e-learning as a means of teaching-learning
      method. 

PMID- 24943523
TI  - Relationship between nursing students' preference for types of teaching materials
      and learning effects of self-learning tool.
AB  - The purpose of this study was to investigate the relationship between learning
      effects of the self-learning tool for nursing students and types of teaching
      materials. Ten nursing students were asked to perform transfer a patient from bed
      to wheelchair after watching the demo video and practicing 20 minutes. The
      students' performance was evaluated before and after practicing. The students
      were also asked to choose teaching materials that would be developed in the
      future. Out of nine teaching materials, the students chose seven of them.
      Correspondence analysis was conducted between the results of the evaluation of
      students' transfer technique and their preference of teaching materials. The
      results indicated that there was no relationship between the preference of
      teaching materials and the scores of transfer techniques. The authors concluded
      that the self-learning was not affected by the preference of teaching materials. 

PMID- 24943525
TI  - Infusing informatics into interprofessional education: the iTEAM
      (Interprofessional Technology Enhanced Advanced practice Model) project.
AB  - The iTEAM goal is to prepare advanced practice nurses, physicians and pharmacists
      with the interprofessional (IP) core competencies (informatics, patient centric,
      quality-focused, evidence based care) to provide technology enhanced
      collaborative care by: offering technology enhanced learning opportunities
      through a required informatics course, advanced practice courses (team based
      experiences with both standardized and virtual patients) and team based clinical
      experiences including e-health experiences. The innovative features of iTEAM
      project will be achieved through use of social media strategies, a web accessible
      Electronic Health Records (EHRs) system, a Virtual Clinic/Hospital in Second
      Life, various e-health applications including traditional telehealth tools and
      consumer oriented tools such as patient portals, social media consumer groups and
      mobile health (m-health) applications for health and wellness functions. It
      builds upon the schools' rich history of IP education and includes clinical
      partners, such as the VA and other clinical sites focused on care for underserved
      patient populations. 

PMID- 24943524
TI  - A virtual platform for electronic health record (EHR) education for nursing
      students: moving from in-house solutions to the cloud.
AB  - There is a need to develop cost effective ways to bring hands-on education about
      essential information technologies, such as electronic health record (EHR)
      systems to nursing students, nursing faculty and practitioners. This is
      especially the case as worldwide there is an increased deployment of these
      systems and they are transforming the practice of healthcare. However, due to
      technical, financial and knowledge limitations, many nursing schools and programs
      do not have an adequate way to bring such technology into their classes and
      curricula. In this paper we describe an approach to developing Web-based EHR
      education that allows students from any Web-accessible location to access and
      work with real EHR systems remotely over the Internet for learning purposes. In
      this paper we describe our work in moving this approach to a cloud-based solution
      to allow access to EHRs for educational purposes from any location with Web
      access and to do so in a way that is both educationally sound and cost effective.

PMID- 24943526
TI  - A cloud computing based platform for sleep behavior and chronic diseases
      collaborative research.
AB  - The objective of this study is to propose a Cloud Computing based platform for
      sleep behavior and chronic disease collaborative research. The platform consists
      of two main components: (1) a sensing bed sheet with textile sensors to
      automatically record patient's sleep behaviors and vital signs, and (2) a service
      oriented cloud computing architecture (SOCCA) that provides a data repository and
      allows for sharing and analysis of collected data. Also, we describe our
      systematic approach to implementing the SOCCA. We believe that the new cloud
      based platform can provide nurse and other health professional researchers
      located in differing geographic locations with a cost effective, flexible, secure
      and privacy-preserved research environment. 

PMID- 24943527
TI  - Using a data mining approach to discover behavior correlates of chronic disease:
      a case study of depression.
AB  - The purposes of this methodological paper are: 1) to describe data mining methods
      for building a classification model for a chronic disease using a U.S. behavior
      risk factor data set, and 2) to illustrate application of the methods using a
      case study of depressive disorder. Methods described include: 1) six steps of
      data mining to build a disease model using classification techniques, 2) an
      innovative approach to analyzing high-dimensionality data, and 3) a visualization
      strategy to communicate with clinicians who are unfamiliar with advanced
      statistics. Our application of data mining strategies identified childhood
      experience living with mentally ill and sexual abuse, and limited usual activity
      as the strongest correlates of depression among hundreds variables. The methods
      that we applied may be useful to others wishing to build a classification model
      from complex, large volume datasets for other health conditions. 

PMID- 24943528
TI  - From capturing nursing knowledge to retrieval of data from a data warehouse.
AB  - The purpose of the project was to capture nursing data and knowledge, represent
      it for use and re-use by retrieval from a data warehouse, which contains both
      clinical and financial hospital data. Today nurses at LUH use standardized
      nursing terminologies to document information related to patients and the nursing
      care in the EHR at all times. Pre-defined order sets for nursing care have been
      developed using best practice where available and tacit nursing knowledge has
      been captured and coded with standardized nursing terminologies and made explicit
      for dissemination in the EHR. All patient-nursing data is permanently stored in a
      data repository. Core nursing data elements have been selected for transfer and
      storage in the data warehouse and patient-nursing data are now captured, stored,
      can be related to other data elements from the warehouse and be retrieved for use
      and re-use. 

PMID- 24943529
TI  - Improving inpatient fall prevention strategies using interactive data repository
      information system.
AB  - Observing the pattern changes of inpatient fall and validating the Fall
      Prevention Tool Kit (FPTK) are essential for developing fall prevention
      strategies. However, the work requires the collection, calculation, and
      comparison of large amount of data. The information is often scattered in diverse
      information systems and lack of integration, which makes the work difficult and
      often neglected. This study demonstrates the development of an Interactive Data
      Repository System (IDRS) and uses it in the analysis of the pattern changes of
      inpatient fall within the institute, and validates efficiency of the FPTK across
      time. This study collected the incident data of year 2011 and compared it with
      the previous analysis in 2001. The result shows that reasons for patient fall had
      turned from physical disability to impaired conscious or cognition. The scoring
      result may be too sensitive in identifying patient falls. Patients with high
      scores needed to reinforce in functional strength. 

PMID- 24943530
TI  - Identifying barriers for implementation of computer based nursing documentation.
AB  - This study was undertaken in the planning phase for the introduction of a
      comprehensive computer based nursing documentation system at Erlangen University
      Hospital. There, we expect a wide range of difficult organizational changes,
      because the nurses currently neither used computer based nursing documentation
      nor did they follow strongly the nursing process model within paper based
      documentation. Thus we were eager to recognize potential pitfalls early and to
      identify potential barriers for digital nursing documentation. In a questionnaire
      study we surveyed all German university hospitals for their experience with the
      implementation of computer based nursing documentation implementation. We
      received answers from 11 of the 23 hospitals. Furthermore we performed a
      questionnaire study about expectations and fears among the nurses of four pilot
      wards of our hospital. Most respondents stated a positive attitude towards the
      nursing process documentation, but many respondents note technical (e.g. bad
      performance of the software) and organizational barriers (e.g. lack of time). 

PMID- 24943531
TI  - Clinical documentation improvement for outpatients by implementing electronic
      medical records.
AB  - This observational study was conducted before and after implementing an
      electronic medical record (EMR) system to evaluate the change in outpatient
      workflow by implementation of EMR and the effectiveness of clinical documentation
      improvement (CDI). The number of hours for patient care increased by 89.2% (p <
      .05) and the hours for writing medical records after consulting decreased after
      implementation of EMR by 27.3% (p < .01). Implementation of EMR reduced nurses'
      workload to handle medical records by 78.8 (p < .05) but not changed for
      physicians. The necessary change in the information management process occurred
      after using the CDI indicator. We recommend that the "working hours of health
      professionals" and "handling hours for information resources" should be used
      widely as CDI indicators to improve workflow when implementing EMR. 

PMID- 24943532
TI  - Promoting meaningful use of health information technology in Israel: ministry of
      health vision.
AB  - The Ministry of Health (MOH) of Israel has overall responsibility for the
      healthcare system. In recent years the MOH has developed strong capabilities in
      the areas of technology assessment and prioritization of new technologies. Israel
      completed the transition to computerized medical records a decade ago in most
      care settings; however, the processes in Israel was spontaneous, without
      government control and standards settings, therefore large variations among
      systems and among organizations were created. Currently, the main challenge is to
      convert the information scattered in different systems, to organized, visible
      information and to make it available to various levels in health management. The
      MOH's solution is of implementing a selected information system from a specific
      vendor, at all the hospitals and all HMO's clinics, in order to achieve
      interoperability. The sys-tem will enable access to the patient's medical record
      history from any location. 

PMID- 24943533
TI  - The impact of electronic health records on client safety in aged care homes.
AB  - This study collects and critically reviews the published literature to synthesize
      the risk factors for client safety in residential aged care and the potential
      contributions of electronic health records to reducing these risks. Three major
      types of risk factors for client safety were identified: risk factors related to
      the person's health; those related to the health and aged care system serving the
      person and those related to human error. Multiple strategies at all levels of an
      aged care organization are needed to reduce risks and improve client safety.
      Electronic health records can be one of the effective organizational mechanisms
      because it improves access to better information and integrates intelligent
      functions to support point-of-care decision making. 

PMID- 24943534
TI  - Mockup design of personal health diary app for patients with chronic kidney
      disease.
AB  - Health self-management is important in the care of patients with chronic kidney
      disease. It is possible to improve the efficiency of patient self-management
      through the use of mobile technology and related software. This study is divided
      into three stages: 1. analysis of need: through observation, interview and
      content analysis of the chronic kidney disease health management manual; 2.
      design of system prototype: establish interface and system function; 3. prototype
      evaluation: evaluate whether the prototype designed by this study meets user
      needs. The system prototype includes: daily record, laboratory examination
      results, trend graphs, information search, sharing, communications and settings.
      Prototyping is done with Pencil Project for interface design and linking. The
      prototype is then exported in PDF format for mock-up simulation. Evaluation
      results: overall score was 4.01+/-0.60 leaning towards "agree", the highest score
      was ease of use (4.25+/-0.6), followed by easy to learn (4.15+/-0.68), acceptance
      (4.01+/-0.61), reliability (3.87+/-0.6) and functionality (3.83+/-0.49). The
      results show positive attitude towards the system. 

PMID- 24943535
TI  - Appreciating the Persona paradox: lessons from participatory design sessions with
      HIV+ gay men.
AB  - Eliciting user requirements from HIV-positive gay men who smoke can be
      challenging. This is because of the complex relationship between social stigma
      and gender identities (e.g., gay, masculine, HIV+, and smoking status). Inspired
      to engage HIV-positive gay men in the development of a web-assisted tobacco
      intervention, we used personas as a main communication tool in our participatory
      design sessions. Personas are characters created by users that embody part of
      their own behaviours, thoughts, and motivations. In an apparent paradox, this
      article is a description of how the use of personas to ensure less realistic self
      representation provided an impetus for more self-disclosure. Findings and
      feedbacks from this study reveal that personas are an effective design tool to
      engage users in sensitive topics. Implications for future work are also
      discussed. 

PMID- 24943536
TI  - Development of an electronic instruction system to promote multidisciplinary
      teams.
AB  - While the provision of medical care incorporating safety measures, etc. that can
      earn the trust of the people, patients in particular, is required, the content of
      instruction is diverse, complex and rapidly increasing in volume along with the
      sophistication and specialization of medical care. However, until now, the
      development of electronic instruction systems has lagged behind in the
      development of HIS. All instructions must be linked to orders and the input of
      the implementation of instructions in the electronic instruction system
      incorporated into medical accounting. The system must aim at integrating
      physician and nursing records and be of a specification that can ensure
      reliability and efficiency. We report on the efforts at Kagoshima University
      Hospital to systematize instruction in order to promote multidisciplinary teams. 

PMID- 24943537
TI  - Exploring factors related to the adoption and acceptance of an internet-based
      electronic personal health management tool (EPHMT) in a low income, special needs
      population of people living with HIV and AIDS in New York City.
AB  - Access to personal health information assists efforts to improve health outcomes
      and creates a population of active and informed health consumers. Understanding
      this significance, Healthy People 2020 retained, as a Focus Area, the need for
      improved interactive Health Communication and HIT. Attainment of this goal
      includes increasing the use of Internet-based electronic personal health
      management tools (EPHMT). Health information management, essential for favorable
      health outcomes, can be problematic in low income, special needs populations with
      complex chronic illnesses such as HIV/AIDS. Furthermore, barriers to the adoption
      and acceptance of an EPHMT in such populations have not been well explored. The
      current study seeks to explore the usability of an EPHMT entitled MyHealthProfile
      and to identify perceived health information needs in a vulnerable population of
      people living with HIV and AIDS (PLWH) that have access to an EPHMT through their
      Medicaid Special Needs Plan. 

PMID- 24943538
TI  - Evaluation of use of electronic patient controlled analgesia pumps to improve
      patient safety in an academic medical center.
AB  - Patient controlled analgesia (PCA) and Patient-controlled epidural analgesia
      (PCEA) pumps are methods of pain control with complex smart infusion devices and
      are widely used in hospitals. Smart PCA/PCEA pumps can be programmed with the
      dose and rate of medications within pre-set ranges. However, adverse effects have
      been reported associated with these pumps' use. In this paper, we describe a
      prevalence observational study where observers used an electronic data collection
      tool to record pump settings and medications with PCA pumps, corresponding
      medication orders to identify errors. The results showed that there were many
      labeling and tubing change tag errors, which were a violation of hospital policy.
      A few potential harmful medication errors were identified but no critical errors.
      Study results suggest the importance of a standard process of PCA pump use. Next
      steps include implementing a safety bundle for improving PCA practice to support
      safe and effective pain management. 

PMID- 24943539
TI  - Evaluation of ambient assisted living interventions--which tool to choose?
AB  - This paper discusses suggested evaluation frameworks' appropriateness for a study
      introducing Ambient Assisted Living (AAL) interventions. Specifically, we look at
      how well proposals cover these dimensions: impact on society, impact on
      professionals, and impact on patients. We discuss three widely used approaches
      for such assessments: RE-AIM, MAST, and UTAUT. Our assessment showed careful
      selection of elements from all three models seems needed to sufficiently cover
      the dimensions. RE-AIM provides a broad framework; MAST adds aspects of
      transferability and ethics, and UTAUT adds perception of technology and future
      use. All these approaches lack pivotal aspects concerning inclusion of patients'
      or citizens' point of view in a study's planning phase. To ensure rigor and
      include meaningful use from citizens' perspective, we added these aspects to our
      study. 

PMID- 24943540
TI  - Building a common ground on the clinical case: design, implementation and
      evaluation of an information model for a Handover EHR.
AB  - Handovers need a common ground on the clinical cases between the members of the
      successive shifts to establish continuity of care. Conventional electronic
      patient record systems (EHR) proved to be only insufficiently suitable for
      supporting the grounding process. Against this background we proposed a basic
      concept for a handover EHR that extends general EHRs in particular openEHR based
      systems. The resulting handover information model was implemented in a database
      and evaluated based on 120 clinical cases. The information items of these cases
      could be mapped successfully to the model, however, the new class "anticipatory
      guidance" needed to be introduced. The evaluation also demonstrated the
      importance of highly aggregated information on the clinical case, opinions and
      meta-information such as the relevance of an item during handovers. Based on
      these findings, in particular the handover database, handover EHR applications
      are currently developed to support the grounding process. 

PMID- 24943541
TI  - Improving the coordination of patients' medication management: a regional Finnish
      development project.
AB  - In this paper, we present an overview of activities and results from a regional
      development project in Finland. The aim in this project was to analyze how
      healthcare providers produce and receive information on a patient's medication,
      and to identify opportunities to improve the quality, effectiveness, availability
      and collaboration of social and healthcare services in relation to medication
      information. The project focused on the most important points in patients'
      medication management such as home care and care transitions. In a regional
      development project, data was gathered by interviews and a multi professional
      workshop. The study revealed that medication information reached only some
      professionals and lay caregivers despite electronic patient record (EPR) systems
      and tools. Differences in work processes related to medication reconciliation and
      information management were discussed in the group meeting and were regarded as a
      considerable risk for patient safety. 

PMID- 24943542
TI  - Representing nursing guideline with unified modeling language to facilitate
      development of a computer system: a case study.
AB  - To provide best recommendations at the point of care, guidelines have been
      implemented in computer systems. As a prerequisite, guidelines are translated
      into a computer-interpretable guideline format. Since there are no specific tools
      to translate nursing guidelines, only a few nursing guidelines are translated and
      implemented in computer systems. Unified modeling language (UML) is a software
      writing language and is known to well and accurately represent end-users'
      perspective, due to the expressive characteristics of the UML. In order to
      facilitate the development of computer systems for nurses' use, the UML was used
      to translate a paper-based nursing guideline, and its ease of use and the
      usefulness were tested through a case study of a genetic counseling guideline.
      The UML was found to be a useful tool to nurse informaticians and a sufficient
      tool to model a guideline in a computer program. 

PMID- 24943543
TI  - Developing the structured knowledge model to navigate the nurses' thinking
      process in their professional judgment and action.
AB  - Authors have defined the function of the nursing observation as "monitoring the
      onset and course of health problems" and that of nursing action as "preventing
      health problems". We have also identified three foci of the nursing observation
      and nursing action respectively. The foci of nursing observation are: "signs and
      symptoms related to the diseases", "complications related to the invasive medical
      procedures such as surgery" and "adverse effects related to the pharmacotherapy".
      Those of nursing action are: "nursing care to fulfill the needs arising from the
      diseases and the medical interventions", "nursing care to prevent the
      complications", and "nursing care to prevent the adverse effects". Finally, we
      have categorized hospitalized patients' conditions into "pre-surgery", "post
      surgery" and "rehabilitative phase" for the surgical patients and "severe",
      "moderate" and "mild" for non-surgical ones. Using these frameworks, we have
      developed the structured knowledge model for a number of diseases and medical
      interventions. 

PMID- 24943545
TI  - An integrated approach to safety-driven and ICT-enabled process reengineering:
      methodological advice and a case study.
AB  - Patient safety is a central concern inside any healthcare environment. With the
      progress of Information and Communication Technologies (ICTs), new solutions have
      become available to support care and management processes. Analyzing process
      risks helps identifying areas of improvement and provides ICT-solutions design
      with indications on what portions of the process need primary interventions.
      Understanding the link between process reengineering, technology assessment of
      enabling technologies and risk management allows user acceptance and patient
      safety improvements. Fondazione IRCCS Istituto Nazionale dei Tumori (INT), offers
      a good example of process reengineering driven by the purpose of increasing
      patient safety, enabled by new technologies. A pillar of the evolution of ICT
      process support at INT is based on Radio Frequency Identification technologies,
      implemented to identify and trace items and people across processes. This paper
      will present an integrated approach, based on process reengineering methodologies
      and risk assessment studies, and methodological advice applied to a case of
      surgical kits management procedures. 

PMID- 24943544
TI  - FinCC and the National Documentation Model in EHR--user feedback and development
      suggestions.
AB  - The structure of the Finnish nursing documentation model is based on the decision
      making process and a standardized nursing terminology: Finnish Care
      Classification (FinCC). Nearly 20,000 nurses use the FinCC although not all
      healthcare organizations utilize it. Development projects for the common national
      nursing documentation framework have been carried out, for example, in 2010-2011
      the aim of a project by the Ministry of Social Affairs and Health and the
      National Institute of Health and Welfare was to suggest recommendations for the
      Finnish nursing documentation model. The final report of the project was sent to
      different organizations all over the country for further feedback statements. The
      aim of this paper is to summarize the message of the statements (n=37) from
      primary and specialized care, universities including universities of applied
      science, professional nursing associations, trade unions and national
      authorities. Development suggestions for the FinCC and electronic health records
      will be introduced. 

PMID- 24943546
TI  - Collaborative software development for a Brazilian telehealth program.
AB  - Telehealth services in the State of Pernambuco, Brazil are led by the Telehealth
      Center (RedeNUTES) and based on HealthNet 2.0 software. Among the tele-assistance
      services, health professionals have clinical discussions focused on second
      opinions. This paper reports the experience in a PhD study through mixed-methods,
      to evaluate the telehealth services, planning and modeling a new tool to improve
      a telehealth system. We described the nurse's role in each phase of this study.
      The method of User-Centered Design was explored in three phases as Identification
      of work process, User's perception and collaborative modeling, Observational
      usability study. The main frame was based on collaborative techniques as
      Collaborative Prototype Design Process, cognitive walkthrough, and thinking
      aloud. The users also identified all usability problems identified by the
      evaluators. The methods were useful in identifying usability problems, and easy
      to employ using standard equipment and software thus a relatively low cost
      approach to usability testing. 

PMID- 24943547
TI  - Development and implementation of IT require focus on user participation,
      acceptance and workflow.
AB  - The study "Online Care" follows a municipal project "Online Welfare" where a
      nurse's presence in the citizen's own home was replaced by online communication.
      The paper is based on a citizen's perspective and seeks to develop meaningful
      workflow for the benefit of citizens with medical problems. The study examines
      five citizens' opinions on whether online communication in a meaningful way
      supports the citizens in what they associate with a good life. In addition,
      relatives and the citizen's nurse were interviewed individually concerning the
      same issues as the citizens. The study has been approved by the Danish System of
      Ethics in Science and is conducted in collaboration with Aalborg University,
      Aalborg Municipality and DanAge, (NGO). The municipality's goal of efficiency and
      financial savings regarding "Online Welfare" was not honored due to insufficient
      network infrastructure and technical problems. An adoption barrier was that the
      municipality did not determine the efforts and the goal of the project, who could
      benefit from participating and the requirements of the professionals and the
      organization including ethical considerations.It was difficult to find citizens
      who were willing to participate. Citizens, who were included in the study
      accepted and adopted the technology however, "Online Welfare" could not replace
      the care they used to receive. Therefore, the offer was perceived as an
      "appendix" which tended to meaninglessness by some of the citizens.The nurses'
      perception of nursing care and their limited IT skills was a barrier to
      acceptance, adoption and development of technology opportunities in nursing. The
      citizens' disability, the screen appearance, and the technology setup meant that
      the citizens perceived poor usability of the equipment. The study showed a change
      in workflow, as the cooperation between the citizen and the professional
      developed. New roles occurred for the professionals.The citizens had many ideas
      concerning the development of the technology and the study recommends that users
      are involved in the development and implementation of welfare technology and
      telemedicine. The relatively small sample size of the study shows findings that
      must be clarified by further research. 

PMID- 24943548
TI  - Leadership strategies for improved nursing synergy between informatics and
      telehealth.
AB  - The goal of best practice, best possible health care worldwide is shared by
      nurses and all involved with eHealth today. The purpose of this paper is to
      characterize the similarities and differences between informatics and telehealth
      from a nursing perspective, and to advocate for leadership strategies that would
      bring the strengths of each group to a more synergistic, collaborative
      professional model for the benefit of both groups. After comparing telehealth and
      informatics nursing and looking for commonalities, suggestions are made for
      bridging the gap between the two groups. Potential strategies include identifying
      leaders, using conflict avoidance techniques, and pursuing coaching and mentoring
      opportunities across the gap to enhance the professional standing and
      contributions of both groups. An added consideration would be to have joint
      conferences wherein the strengths, challenges and knowledge repositories of
      informatics and telehealth could be mutually appreciated. 

PMID- 24943549
TI  - Toward an integrated health data display for aging in place.
AB  - In a typical aging-in-place setting, electronic medical record, telemedicine
      data, and sensor data are used by different groups of decision makers, but the
      data may not be viewed in a holistic display to promote clinical decision making.
      Employing a user-centered design and evaluation framework, we analyzed relational
      data displays of congestive heart failure and provided an in-depth description of
      user characteristics, preferences, systems functionality, basic tasks and
      effective representations in such an information distributed setting. As a
      result, the prototypical design demonstrates our effort toward an integrated data
      display for chronic disease management in long-term care and clinical decision
      support which would enhance aging in place. 

PMID- 24943550
TI  - Developing and testing a mobile application programme to support self-management
      in patients with stable angina: a feasibility study protocol.
AB  - This study aims to develop and test the feasibility of a 12-week Mobile
      Application Programme (M.A.P.) to support self-management in cardiac patients
      with stable angina. A Mobile Application Programme will be developed by the study
      team. A pilot randomized controlled trial will be adopted to examine the
      feasibility and potential effectiveness of the M.A.P.. A convenience sample of 40
      stable angina patients recruited from the National University Heart Centre will
      be randomly assigned either to the 12-week M.A.P. intervention group or the
      control group. Data will be collected at baseline, at the 4th and 12th week of
      the programme. At the end of the intervention period, a process evaluation will
      be conducted to further assess the acceptability, usability, strengths and
      weaknesses of the M.A.P. intervention based on the participants' perspectives.
      All quantitative data obtained will be analysed using IBM SPSS 21.0, while
      content analysis will be used for qualitative datasets. 

PMID- 24943551
TI  - The national mobile health worker project in England.
AB  - Community services provide essential care to many, often vulnerable, people,
      families and communities along the spectrum from health promotion to end of life
      care. The Mobile Health Worker Project is part of a larger project, the
      Transforming Community Services programme, which was established to support
      providers make changes to service provision that would provide better health
      outcomes, as well as increasing efficiency through the use of technology. This
      paper draws on the results of the two phase Mobile Health Worker project which
      involved 11 sites around England, the aim of which was to understand the
      requirements of mobile working. The results demonstrate that increased
      productivity and efficiency can be achieved by making changes to working
      processes. The project also provides guidance to increase the rate of mobile
      working adoption by providing a solid economic basis for investment in and
      deployment of mobile solutions to community organisations. 

PMID- 24943552
TI  - Developing mobile support system for dynamic integrated community-based
      screening.
AB  - Screening evaluations can effectively detect unrecognized health problems in
      individuals. Current integrated community-based multiple screening manually fill
      out handwritten forms. The motivation of the system developed in this study is to
      provide a method for participants to quickly fill out community health screening
      questionnaire prior to participating in the screening event. This study is
      divided into two stages: 1. System development and design compatible with the
      needs of elderly users, planning and creation of system architecture based on the
      requirements of the community-based integrated screening questionnaire; 2. System
      evaluation: provide the created App to users for evaluation of user satisfaction.
      The system prototype design includes the use of "3+1 hierarchical grid interface
      design", incorporating all the questions in the community screening survey and
      the details on interface design takes note of the needs of elderly users, the
      questionnaire used is a 5-point Likert scale. Assessment results: overall score
      of 4.12+/-0.31 leaning towards "Agree" with perceived usefulness having the
      highest score (4.32+/-0.17), second being reliability (4.17 +/- 0.1), followed in
      order by satisfaction (4.14 +/- 0.0), perceived ease of use (4.07 +/- 0.21),
      learnability (4.0 +/- 0.07), and acceptance (3.79 +/- 0.81). Based on these
      results, the participants held a positive attitude towards the system. 

PMID- 24943553
TI  - Technology combined with a counseling protocol to stimulate physical activity of
      chronically ill patients in primary care.
AB  - An iterative user-centered design method was used to develop and test mobile
      technology (the It's LiFe! tool/monitor) embedded in primary care, followed by a
      three months feasibility study with 20 patients and three nurses. The tool
      consists of an accelerometer that transfers data to an app on a Smartphone, which
      is subsequently connected to a server. Physical activity levels are measured in
      minutes per day compared to pre-set activity goals, which are set by patients in
      dialogue with nurses. Nurses can monitor patients' physical activity via a
      secured website. The counseling protocol is based on the Five A's model and
      consists of a limited number of behavior change consultations intertwined with
      interaction with and responses from the tool. The technology supports nurses when
      performing physical activity counseling. Provided that no connectivity problems
      occur, the It's LiFe! intervention is feasible, and its longitudinal effects will
      be tested in a cluster RCT. 

PMID- 24943554
TI  - Development of a prediction model for early diagnosis of not passing the national
      council of licensure examination for registered associate degree nurses.
AB  - Passing the national licensure examination for registered nurses (NCLEX-RN) in
      the US is a critical outcome of the nursing program. Research has been conducted
      to identify which nursing students are at risk for not passing the NCLEX-RN test.
      The purpose of this study was to investigate whether any of several student
      covariates can be used to accurately identify associate in science in nursing
      (ASN) students that are at-risk for failing the NCLEX-RN test. Covariates
      included in the study were demographics, students' pre-admission grade point
      average (GPA), the scores of test of essential skills (TEAS), and the assessment
      technologies institute(r) (ATI)'s comprehensive scores for a pre-RN examination
      test. Chi-squared automatic interaction detection, or CHAID analysis, was used to
      develop the model. One covariate, ATI comprehensive test scores, was found to
      accurately identify all at-risk ASN students. The model explained that students
      identified as "at-risk" had a failure rate nearly two-and-a-half times as high as
      the general population. 

PMID- 24943555
TI  - Refining process of nursing skill movie manual by peer comments of social network
      system.
AB  - The nursing practical knowledge represented by nursing skill is highly tacit and
      is therefore difficult to verbalize. The purpose of this study is to build a new
      learning community for nursing education (nursing social e-learning model) that
      is refined and developed autonomously and continuously. We used the social
      network system (SNS) that can be participated in a variety of stakeholder of
      medical personnel in order to hear comments for the content of learning to
      practice nursing skill. We had the nurses make the nursing skill movie manual.
      Through this process to get the opinions about the movie contents from others, we
      inspected what kind of opinions and feelings occurred to the nurses. As a result,
      the nurses were able to see objectively the own nursing skills, to do self
      reflection. They had the awareness to improve the nursing skills. 

PMID- 24943556
TI  - Considerations for design of an e-learning program augmenting advanced geriatric
      nurse practitioner's clinical skills training.
AB  - E-learning programs offer learners flexibility, more control over their learning
      experience, possibilities for repetition and allows for learning to be more
      individualized compared to traditional teaching methods. This paper presents
      considerations for an interdisciplinary project to design an e-learning program
      for graduate students enrolled in a master's program in Advanced Geriatric
      Nursing. The e-learning program offers new opportunities for learners to apply
      theoretical knowledge and develop their skills in the process of collaborative
      knowledge creation. A model based on the systematic development of instruction
      and learning and a pedagogical framework for e-learning has guided the design
      process. This paper explains how the e-learning program was created and how
      content was developed and implemented in an e-learning environment. 

PMID- 24943557
TI  - Challenges associated with the secondary use of nursing data.
AB  - There is a prevailing 'collect once, use many times' view of clinical data and
      its secondary use. This study challenges this view through an assessment of the
      degree to which the International Classification for Nursing Practice (ICNP)
      might be used to provide raw data for the Belgian Nursing Minimum Data Set (B
      NMDS). A mapping exercise identified exact matches between ICNP and B-NMDS for
      just 8% of B-NMDS care descriptions; no matches at all for 23%; possible broader
      matches in ICNP for 55%; possible narrower matches for 8%; and a possible broader
      and narrower match for 1%. Refining ICNP content and developing and implementing
      purposive data sets or catalogues that accommodate both ICNP concepts and B-NMDS
      care descriptions would lay the foundations for the potential re-use of primary
      ICNP-encoded data in populating the B-NMDS. One unexpected result of the study
      was to re-affirm the utility of ICNP as a reference terminology. 

PMID- 24943558
TI  - The use of standardized terminology to represent nursing knowledge: nursing
      interventions relevant to safety for patients with cancer.
AB  - The study is to represent knowledge by identifying frequently used nursing
      interventions in term of standardized nursing terminology (SNT) in the Electronic
      Health Records (EHRs) relevant to Safety for Patients with Cancer. We include
      2,237 patients and found 11,804 nursing interventions in total. There are 100
      identical interventions in the study. We identify eleven nursing interventions
      from four oncology units over 7 month observation. For the most four frequent
      nursing interventions (Fall Prevention, Infection Control, Infection Protection,
      and Pressure Management), we also report the mean of age, the mean of length of
      stay, and their frequency of outcome rating , outcome rating at admission and at
      discharge that link to outcome. These studies demonstrate the strengths of SNT in
      clinical practice. The findings are valuable to clinical practice, education and
      future research. 

PMID- 24943559
TI  - Graph based model to support nurses' work.
AB  - Health care is a knowledge-based community that critically depends on knowledge
      management activities in order to ensure quality. Nurses are primary stakeholders
      and need to ensure that their information and knowledge needs are being met in
      such ways that enable them, to improve the quality and efficiency of health care
      service delivery for all subjects of health care. This paper describes a system
      to help nurses to create nursing care plan. It supports focusing nurse's
      attention on those resources/solutions that are likely to be most relevant to
      their particular situation/problem in nursing domain. System is based on multi
      relational property graph representing a flexible modeling construct. Graph
      allows modeling a nursing domain (ontology) and the indices that partition domain
      into an efficient, searchable space where the solution to a problem is seen as
      abstractly defined traversals through its vertices and edges. 

PMID- 24943560
TI  - The computerized OMAHA system in microsoft office excel.
AB  - The OMAHA System was adopted as the documentation system in an interventional
      study. To systematically record client care and facilitate data analysis, two
      Office Excel files were developed. The first Excel file (File A) was designed to
      record problems, care procedure, and outcomes for individual clients according to
      the OMAHA System. It was used by the intervention nurses in the study. The second
      Excel file (File B) was the summary of all clients that had been automatically
      extracted from File A. Data in File B can be analyzed directly in Excel or
      imported in PASW for further analysis. Both files have four parts to record basic
      information and the three parts of the OMAHA System. The computerized OMAHA
      System simplified the documentation procedure and facilitated the management and
      analysis of data. 

PMID- 24943561
TI  - From unmet clinical need to entrepreneurship: taking your informatics solution to
      market.
AB  - This paper will describe the process for taking a decision support solution to
      market as a start-up business. The nurse inventor and Co-Founder of RightCare
      Solutions, Inc. will share the steps from answering a clinical question, to
      registering an invention, creating a business plan and company, obtaining venture
      funding, and launching a commercial product. We will share positives about the
      experience such as how to get start-up funds, gaining national exposure and
      access to an excellent team, disseminating your work broadly, further enhancing
      the product, and obtaining equity, and financial rewards. We will discuss cons
      such as losing control, dilution of ownership, and conflict of interest. This
      paper will encourage nurse informaticians to think differently and learn about
      the steps in the process from an experienced team. 

PMID- 24943562
TI  - Physician and consumer acceptance of the traditional chinese medicine clinical
      practice support system (TCMCPSS).
AB  - Although ICT-enabled clinical practices have been widely accepted by the Western
      medical society, informatics applications for traditional Chinese medicine (TCM)
      are under developed. An integrated traditional Chinese medicine clinical practice
      support system (TCMCPSS) has been developed to enhance data integration
      automation and treatment planning decision support of clinical practice of TCM.
      The acceptance of TCMCPSS had been assessed by 26 TCM physicians based on
      information clarity, clinical relevancy, and theoretical relevancy through a
      survey questionnaire using the 5-points Likert Scale. The average acceptance rate
      was 3.76. One hundred and fifty-four participants were recruited for the TCMCPSS
      feasibility study and reported the acceptance rate of 90%. The results indicated
      that while consumers were ready to embrace TCM practice assisted by informatics
      technologies, TCM physicians concerned more about the usefulness of the system
      and preserved caution to adopt TCMCPSS. 

PMID- 24943563
TI  - Reducing errors through a web-based self-management support system.
AB  - Web-based self-management support systems SMSS, can successfully assist a wide
      range of patients with information and self-management support. O or as a stand
      alone service, are e-messages. This study describes how one component of a multi
      component SMSS, an e-message service, in which patients with breast cancer could
      direct questions to nurses, physicians or social workers at the hospital where
      they were being treated, had an influence on safety and continuity of care.
      Ninety-one dialogues consisting of 284 messages were analysed. The communications
      between patients and the healthcare team revealed that the e-messages service
      served as a means for quality assurance of information, for double-checking and
      for coordination of care. We give examples of how an e-mail service may improve
      patients' knowledge in a process of taking control over their own care -
      increasingly important in a time of growing complexity and specialization in
      healthcare. It remains to be tested whether an e-message service can improve
      continuity of care and prevent or mitigate medical mishaps. 

PMID- 24943564
TI  - Hospital nurses' and physicians' use of information sources during their
      production of discharge summaries: a cross-sectional study.
AB  - Hospital nurses' and physicians' production and exchange of accurate information
      between levels of care are crucial for ensuring safe and seamless care for
      patients in transition. We report on a study in which we explored hospital
      providers' use of information sources when they prepared discharge information
      for colleges in the community health-care sector. In this cross-sectional study,
      510 nurses and 236 physicians responded through a questionnaire. Our findings
      show that nurses and physicians use different information sources in patient
      records when they produce their discharge summaries. 

PMID- 24943565
TI  - Nursing informatics competencies: bibliometric analysis.
AB  - Information and communication technology is developing rapidly and it is
      incorporated in many health care processes, but in spite of that fact we can
      still notice that nursing informatics competencies had received limited attention
      in basic nursing education curricula in Europe and especially in Eastern European
      countries. The purpose of the present paper is to present the results of a
      bibliometric analysis of the nursing informatics competencies scientific
      literature production. We applied the bibliometrics analysis to the corpus of 332
      papers found in SCOPUS, related to nursing informatics competencies. The results
      showed that there is a positive trend in the number of published papers per year,
      indicating the increased research interest in nursing informatics competencies.
      Despite the fact that the first paper was published in Denmark, the most prolific
      country regarding the research in nursing informatics competencies is United
      States as are their institutions and authors. 

PMID- 24943566
TI  - A comparison of Australian and Canadian informatics competencies for
      undergraduate nurses.
AB  - Health information technologies (HIT) have changed healthcare delivery. Yet,
      there are few opportunities for student nurses in their undergraduate studies to
      develop nursing informatics competencies. More importantly, many countries around
      the world have not fully specified nursing informatics competencies that will be
      expected of student nurses prior to their graduation from undergraduate nursing
      programs. In this paper the authors compare and contrast the undergraduate
      nursing informatics competencies that were developed by two countries: Australia
      and Canada. They also identify some of the challenges and future research
      directions in the area. 

PMID- 24943567
TI  - Developing entry-to-practice nursing informatics competencies for registered
      nurses.
AB  - Information and communication technologies (ICT) have brought about significant
      changes to the processes of health care delivery and changed how nurses perform
      in clinical, administrative, academic, and research settings. Because the
      potential benefits of ICT are significant, it is critical that new nurses have
      the knowledge and skills in informatics to provide safe and effective care.
      Despite the prevalence of technology in our day to day lives, and the potential
      significant benefits to patients, new nurses may not be prepared to work in this
      evolving reality. An important step in addressing this need for ICT preparation
      is to ensure that new graduates are entering the work force ready for technology
      enabled care environments. In this paper, we describe the process and outcomes of
      developing informatics entry-to-practice competencies for adoption by Canadian
      Schools of Nursing. 

PMID- 24943568
TI  - The relationship of learning motivation, achievement and satisfaction for nurses
      learning simple excel VBA information systems programming.
AB  - This study aims to understand the relationship between participating nurses'
      motivation, achievement and satisfaction before and after they learned to program
      in Excel Visual Basic for Applications (Excel VBA). We held a workshop to train
      nurses in developing simple Excel VBA information systems to support their
      clinical or administrative practices. Before and after the workshop, the
      participants were evaluated on their knowledge of Excel VBA, and a questionnaire
      was given to survey their learning motivation and satisfaction. Statistics
      softwares Winsteps and SPSS were used for data analysis. Results show that the
      participants are more knowledgeable about VBA as well as more motivated in
      learning VBA after the workshop. Participants were highly satisfied with the
      overall arrangement of the workshop and instructors, but didn't have enough
      confidence in promoting the application of Excel VBA themselves. In addition, we
      were unable to predict the participants' achievement by their demographic
      characteristics or pre-test motivation level. 

PMID- 24943570
TI  - Rapid EHR development and implementation using web and cloud-based architecture
      in a large home health and hospice organization.
AB  - Health care organizations have long been limited to a small number of major
      vendors in their selection of an electronic health record (EHR) system in the
      national and international marketplace. These major EHR vendors have in common
      base systems that are decades old, are built in antiquated programming languages,
      use outdated server architecture, and are based on inflexible data models [1,2].
      The option to upgrade their technology to keep pace with the power of new web
      based architecture, programming tools and cloud servers is not easily undertaken
      due to large client bases, development costs and risk [3]. This paper presents
      the decade-long efforts of a large national provider of home health and hospice
      care to select an EHR product, failing that to build their own and failing that
      initiative to go back into the market in 2012. The decade time delay had allowed
      new technologies and more nimble vendors to enter the market. Partnering with a
      new start-up company doing web and cloud based architecture for the home health
      and hospice market, made it possible to build, test and implement an operational
      and point of care system in 264 home health locations across 40 states and three
      time zones in the United States. This option of "starting over" with the new web
      and cloud technologies may be posing a next generation of new EHR vendors that
      retells the Blackberry replacement by iPhone story in healthcare. 

PMID- 24943569
TI  - Opportunities in interdisciplinary care team adoption of electronic point-of-care
      documentation systems.
AB  - We conducted three evaluation studies in community and hospital settings to
      examine point-of-care documentation system adoption among interdisciplinary care
      team clinicians. In the community settings, quantitative methods included
      documentation time-to-completion and a clinician satisfaction survey. Qualitative
      methods included observations and follow-up interviews. Qualitative data and
      quantitative data were merged comparing findings along themes. In the hospitals,
      qualitative scenario testing results indicated clinician system adoption was
      universal, though not always timely. At all sites, mismatch between system
      functionality and workflow was a barrier to clinician system access during
      patient care and reduced clinician efficiency. Clinicians at all settings were
      satisfied with their ability to access other clinicians' notes, without increased
      interdisciplinary team communication. Clinicians did not identify any systems
      impact on patient outcomes. To facilitate adoption, clinicians should see the
      value of using the system as intended by receiving system data feedback that
      shows improvement of patient care and patient safety. 

PMID- 24943571
TI  - Electronic communication experiences of home health care nurses and general
      practitioners: a cross-sectional study.
AB  - Future health care will require suitable means of communication between home
      health care nurses and general practitioners (GPs) to ensure safe care for
      homebound patients. The overall aim of this study was to investigate the
      experiences of home health care nurses and general practitioners using e
      messaging in their communication. We conducted a cross-sectional study with a
      mailed questionnaire. A total of 584 home health care nurses and GPs who used e
      messaging and 495 home health care nurses and GPs who did not use e-messaging
      completed the questionnaire. The results showed that there was high agreement, in
      all the groups, that e-messaging led to better communication quality, better
      access to patient information, and an improved ability to prevent and reduce
      errors and omissions. Nurses reported the most agreement, which led to the
      conclusion that it was the characteristics of the profession rather than the use
      of e-messaging that influenced high agreement. 

PMID- 24943572
TI  - Applied nursing informatics research - state-of-the-art methodologies using
      electronic health record data.
AB  - With the pervasive implementation of electronic health records (EHR), new
      opportunities arise for nursing research through use of EHR data. Increasingly,
      comparative effectiveness research within and across health systems is conducted
      to identify the impact of nursing for improving health, health care, and lowering
      costs of care. Use of EHR data for this type of research requires use of national
      and internationally recognized nursing terminologies to normalize data. Research
      methods are evolving as large data sets become available through EHRs. Little is
      known about the types of research and analytic methods for applied to nursing
      research using EHR data normalized with nursing terminologies. The purpose of
      this paper is to report on a subset of a systematic review of peer reviewed
      studies related to applied nursing informatics research involving EHR data using
      standardized nursing terminologies. 

PMID- 24943573
TI  - Cancer information seeking behaviors and information needs among Korean
      Americans.
AB  - Linguistically and culturally isolated Korean Americans have less access to
      health service and cancer screening tests than all U.S population. Lack of
      adequate cancer information is one of the barriers to undergoing cancer screening
      tests. It is necessary to understand their current cancer information-seeking
      behaviors and information needs if we are to more effectively provide adequate
      cancer information. The purpose of the study was to identify cancer information
      seeking behaviors and information needs among Korean Americans. Data were
      collected from one of the biggest websites for the Korean community in the USA. A
      total of 273 free-texts from January to June 2013 were reviewed and analyzed for
      this study. The extracted terms were categorized based on the coding system. The
      primary reason for asking questions was inquiry followed by sharing experiences.
      The main topics of the postings were categorized as medical or non-medical. In
      relation to types of cancer, breast cancer was the greatest concern. The findings
      from this study can help in establishing more effective strategies to provide
      better cancer information among Korean Americans by assessing their current
      cancer information seeking trends and information needs. 

PMID- 24943574
TI  - Access to internet in rural and remote Canada.
AB  - Canada is the second largest landmass country in the world, but has one of the
      lowest population densities. As of 2011, approximately 19% of the Canadian
      population lives in rural, or remote communities. The purpose of this study was
      to examine differences in rural and urban access to the Internet and device use
      in Canada, and to explore differences in access to broadband between Aboriginal
      and non-Aboriginal communities in Canada. In general rural-dwellers had lower
      levels of Internet access and despite efforts to increase access to high speed
      Internet, Aboriginal communities in some regions have limited access. Future
      research should explore computer and health literacy in the context of rural and
      remote communities in Canada. 

PMID- 24943575
TI  - Promotion of meaningful use of a personal health record in second life.
AB  - Patients today are demanding greater access to and control of their health
      information. Personal Health Records (PHRs) are paving the way for patients to
      update, maintain and share their comprehensive medical information. The
      opportunity to develop and maintain a PHR is equally as important for those
      individuals in the disabled community who face many unique challenges to access
      health information. The project, conducted as part of our graduate course,
      explored the use of Second Life to educate the disabled community on Virtual
      Ability Island (VAI) about the importance of PHRs. The project examined the tools
      needed to offer such a presentation for the disabled community and identified
      legal, ethical, social, or public challenges for PHR use. The project outcomes
      indicated a desire for knowledge and genuine concerns by the attendees regarding
      PHRs. The authors note that more research is needed to make this technology
      available to all. 

PMID- 24943576
TI  - Qualitative study of patient consent for health information exchange in an HIV
      clinic.
AB  - INTRODUCTION/BACKGROUND: Health information exchange (HIE) is the secure,
      electronic transfer and/or accessibility of clinical data among healthcare
      providers. In the United States (US), the consent process for participation
      varies state to state. New York State (NYS) mandates written patient consent. The
      purpose of this study was to examine workflow and perceptions related to
      obtaining HIE consent in an HIV clinic. METHODS: We used contextual inquiry to
      observe the HIE consent-related workflow of four registration clerks for a total
      of 4 hours on two weekdays and subsequently created a flow chart and sequence
      model diagram. Clerks were also interviewed and the resulting narrative data were
      coded into themes. RESULTS: Observational and interview data suggested that
      patient privacy/confidentiality/trust, high volume workflow, and multiple
      competing demands affect the patient HIE consent process. CONCLUSIONS: Additional
      qualitative data needs to be gathered from the perspectives of patients and
      clinicians about the HIE consent process.

PMID- 24943577
TI  - mHealth data collector: an application to collect and report indicators for
      assessment of cardiometabolic risk.
AB  - Traditional population surveys use paper forms that are filled manually by an
      interviewer. This process can take a long time; in comparison, computerizing the
      process reduces time, promotes safety and accuracy of data, improves patient
      care, and offers better control over the compiled information. From this
      perspective, it can be argued that mobile health supports mechanisms for the
      diagnosis, control, and prevention of metabolic diseases. In recent years, mobile
      devices have been applied in several health areas, such as remote monitoring,
      data logging, clinical decision-making, and with applications that can help
      maintain or initiate practices beneficial to individual health and wellbeing.
      However, there is a lack of applications for conducting population surveys. Thus,
      this work presents an application called mHealth Data Collector (mHDC) as a model
      for applications used in population surveys that contain such data as Body Mass
      Index (BMI), health-related issues, and health habit indicators. The design of
      this system occurred through interviews with health professionals who utilized a
      prototyping method to extract requirements. To develop this mobile app, the
      Android platform was adopted and the SQLite database was used to store patients'
      health data. The JExcelAPI and AchartEngine were also employed to generate
      spreadsheets and charts. The mHDC was tested using a case study in a Brazilian
      city. The results indicated that the health team took half the time to interview
      patients. In addition, the system has reduced the use of paper; centered and
      organized data; and allowed quick data recovery and standardization to improve
      the readability of data input. The mHDC proved efficient at collecting,
      analyzing, and safely exporting the results, thus reducing time collecting and
      analyzing the population survey. 

PMID- 24943578
TI  - SAPPIRE: a prototype mobile tool for pressure ulcer risk assessment.
AB  - Accurate assessment and documentation of skin conditions facilitate communication
      among care providers and are critical to effective prevention and mitigation of
      pressure ulcer. We report developing a prototype mobile system called SAPPIRE
      (Skin Assessment for Pressure Ulcer Prevention, an Integrated Recording
      Environment) for an android device to assist nurses with skin assessment and
      documentation at bedside. SAPPIRE demonstrates (1) data documentation conforming
      to the relevant terminology standards, (2) data exchange using Continuity of Care
      Records (CCR) standard and (3) smart display of patient data relevant to risk
      parameters to promote accurate pressure ulcer risk assessment with the Braden
      scale. Challenges associated standardizing assessment data faced during this
      development and the approaches that SAPPIRE took to overcome them are described. 

PMID- 24943579
TI  - A total design and implementation of an intelligent mobile chemotherapy
      medication administration.
AB  - The chemotherapy medication administration is a process involved many
      stakeholders and efforts. Therefore, the information support system cannot be
      well designed if the entire process was not carefully examined and reengineered
      first. We, from a 805-teaching medical center, did a process reengineering and
      involved physicians, pharmacists and IT engineers to work together to design a
      mobile support solution. System was implemented in March to July, 2013. A 6"
      android handheld device with 1D BCR was used as the main hardware. 18 nurses were
      invited to evaluate their perceived acceptance of system based on Technology
      Acceptance Model for Mobile Service Model. Time saved was also calculated to
      measure the effectiveness of system. The results showed positive support from
      nurses. The estimated time saved every year was about 288 nursing days. We
      believe our mobile chemotherapy medication administration support system is
      successful in terms of acceptance and real impacts. 

PMID- 24943580
TI  - Dynamic and accretive composition of patient engagement instruments for
      personalized plan generation.
AB  - Patient engagement is important to help patients become more informed and active
      in managing their health. Effective patient engagement demands short, yet valid
      instruments for measuring self-efficacy in various care dimensions. However, the
      static instruments are often too lengthy to be effective for assessment purposes.
      Furthermore, these tests could neither account for the dynamicity of measurements
      over time, nor differentiate care dimensions that are more critical to certain
      sub-populations. To remedy these disadvantages, we devise a dynamic instrument
      composition approach that can model the measurement of patient self-efficacy over
      time and iteratively select critical care dimensions and appropriate assessment
      questions based on dynamic user categorization. The dynamically composed
      instruments are expected to guide patients through self-management reinforcement
      cycles within or across care dimensions, while tightly integrated into clinical
      workflow and standard care processes. 

PMID- 24943581
TI  - Automatic generation of nursing narratives from entity-attribute-value triplet
      for electronic nursing records system.
AB  - The aim of this study is to develop and evaluate a natural language generation
      system to populate nursing narratives using detailed clinical models. Semantic,
      contextual, and syntactical knowledges were extracted. A natural language
      generation system linking these knowledges was developed. The quality of
      generated nursing narratives was evaluated by the three nurse experts using a
      five-point rating scale. With 82 detailed clinical models, in total 66,888
      nursing narratives in four different types of statement were generated. The mean
      scores for overall quality was 4.66, for content 4.60, for grammaticality 4.40,
      for writing style 4.13, and for correctness 4.60. The system developed in this
      study generated nursing narratives with different levels of granularity. The
      generated nursing narratives can improve semantic interoperability of nursing
      data documented in nursing records. 

PMID- 24943583
TI  - Can big data transform electronic health records into learning health systems?
AB  - In the United States and globally, healthcare delivery is in the midst of an
      acute transformation with the adoption and use of health information technology
      (health IT) thus generating increasing amounts of patient care data available in
      computable form. Secure and trusted use of these data, beyond their original
      purpose can change the way we think about business, health, education, and
      innovation in the years to come. "Big Data" is data whose scale, diversity, and
      complexity require new architecture, techniques, algorithms, and analytics to
      manage it and extract value and hidden knowledge from it. 

PMID- 24943582
TI  - Towards symbiosis in knowledge representation and natural language processing for
      structuring clinical practice guidelines.
AB  - The successful adoption by clinicians of evidence-based clinical practice
      guidelines (CPGs) contained in clinical information systems requires efficient
      translation of free-text guidelines into computable formats. Natural language
      processing (NLP) has the potential to improve the efficiency of such translation.
      However, it is laborious to develop NLP to structure free-text CPGs using
      existing formal knowledge representations (KR). In response to this challenge,
      this vision paper discusses the value and feasibility of supporting symbiosis in
      text-based knowledge acquisition (KA) and KR. We compare two ontologies: (1) an
      ontology manually created by domain experts for CPG eligibility criteria and (2)
      an upper-level ontology derived from a semantic pattern-based approach for
      automatic KA from CPG eligibility criteria text. Then we discuss the strengths
      and limitations of interweaving KA and NLP for KR purposes and important
      considerations for achieving the symbiosis of KR and NLP for structuring CPGs to
      achieve evidence-based clinical practice. 

PMID- 24943584
TI  - Continuity of care with HL7 v3 care record for oncology nursing.
AB  - The Clinical Data Ware House needs to meet three functions: reporting quality
      indicators, clinical research, and continuity of care. This paper reports on one
      function, namely the development and testing of data exchange for continuity of
      nursing care for oncology patients. The proof of principle was carried out using
      system analysis, requirements setting, system design, system development and
      experiment with the application of Health Level 7 version 3 Care Record
      electronic message. A successful testing of the Care Record message was
      conducted, using a case based data-subset for oncology nursing care including
      personal data, pain, weight and vital signs, among others. CONCLUSION: The
      development illustrated that the system components facilitate electronic data
      exchange from hospital to home care, allowing home care nurses to use received
      clinical data in their local system. In an incremental approach this data
      exchange can be enhanced to meet all data and all systems requirements.

PMID- 24943588
TI  - Vitamin B12 deficiency in Jordan: a population-based study.
AB  - BACKGROUND: Vitamin B12 deficiency is highly prevalent worldwide and has been
      linked to hematologic, neurologic and psychiatric diseases. There are a few
      studies regarding vitamin B12 deficiency in developing countries in general and
      in Jordan in particular. OBJECTIVES: The aims of the present study were to assess
      the vitamin B12 status of Jordanians at national level and to identify population
      groups at high risk for vitamin B12 deficiency. METHODS: Vitamin B12 status was
      assessed in a national sample of 5,640 subjects aged >8 years. The study involved
      interviews, laboratory measurements of vitamin B12 and other parameters, and
      physical measurements. The present report deals exclusively with subjects aged
      >18 years (n = 2,847). RESULTS: The percentages of subjects with low (<200 pg/ml,
      n = 857), borderline (201-350 pg/ml, n = 382) and normal vitamin B12 level (>350
      pg/ml, n = 1,608) were 30.1, 13.4 and 56.5%, respectively. Of the 382 subjects
      who had borderline vitamin B12 level, 61 subjects had both increased total
      homocysteine (tHcy; >13 umol/l) and low holocobalamin (<35 pmol/l). Since
      elevated tHcy also indicates folate deficiency, the overall prevalence of vitamin
      B12 deficiency reached 32.2% (31.9% among males and 32.4% among females) after
      adding those 61 subjects to the 857 subjects with low vitamin B12 level.
      CONCLUSION: In conclusion, our study showed that almost one third of Jordanian
      adults have vitamin B12 deficiency with no gender differences. Intake of vitamin
      B complex and multivitamins seems to protect from vitamin B12 deficiency. An in
      depth study of the dietary and eating habits of Jordanians may be needed to
      explain the observed age and regional differences in vitamin B12 deficiency in
      the study population.

PMID- 24943589
TI  - Laminopathy-inducing mutations reduce nuclear import of expressed prelamin A.
AB  - Lamins are structural components of the nuclear lamina and integral parts of the
      nucleoplasm. The tripartite domain structure partitions the molecule into an
      amino-terminal head, central rod and a carboxy-terminal tail domain. The tail
      domain contains a nuclear localization sequence and in most lamins an additional
      CaaX motif, which is necessary to post-translationally process prelamin to mature
      lamin. As players of nuclear and cellular integrity, lamins must possess
      unrestrained access to the nucleus. To study whether nuclear trafficking of
      lamins is compromised in laminopathies, we determined relative nuclear import
      activities between expressed prelamin A and selected laminopathy-inducing mutants
      thereof. Furthermore, the impact of inhibition of maturation on nuclear import of
      expressed prelamin A was examined. To perform quantitative transport
      measurements, import competent but lamina incorporation-deficient GFP- or DsRed
      tagged prelamin A deletion mutants were used, which lacked the head and rod
      domain (DeltaHR-prelamin A). Nuclear accumulation of DeltaHR-prelamin A carrying
      the lipodystrophy and metabolic syndrome-inducing mutations R419C and L421P or
      progeria-causing deletions was significantly reduced, but that of the maturation
      deficient mutant DeltaHR-prelamin A SSIM was significantly increased. In the case
      of the full length prelamin A mutants R419C and L421P altered subcellular
      localization and reduced lamina incorporation were detected, with the prelamin A
      binding protein Narf being redistributed into R419-containing aggregates. The
      results suggest that impaired nuclear transport of certain prelamin A mutants may
      represent a contributing factor in the pathogenesis of certain laminopathies. 

PMID- 24943590
TI  - Disruption of both nesprin 1 and desmin results in nuclear anchorage defects and
      fibrosis in skeletal muscle.
AB  - Proper localization and anchorage of nuclei within skeletal muscle is critical
      for cellular function. Alterations in nuclear anchoring proteins modify a number
      of cellular functions including mechanotransduction, nuclear localization,
      chromatin positioning/compaction and overall organ function. In skeletal muscle,
      nesprin 1 and desmin are thought to link the nucleus to the cytoskeletal network.
      Thus, we hypothesize that both of these factors play a key role in skeletal
      muscle function. To examine this question, we utilized global ablation murine
      models of nesprin 1, desmin or both nesprin 1 and desmin. Herein, we have created
      the nesprin-desmin double-knockout (DKO) mouse, eliminating a major fraction of
      nuclear-cytoskeletal connections and enabling understanding of the importance of
      nuclear anchorage in skeletal muscle. Globally, DKO mice are marked by decreased
      lifespan, body weight and muscle strength. With regard to skeletal muscle, DKO
      myonuclear anchorage was dramatically decreased compared with wild-type, nesprin
      1(-/-) and desmin(-/-) mice. Additionally, nuclear-cytoskeletal strain
      transmission was decreased in DKO skeletal muscle. Finally, loss of nuclear
      anchorage in DKO mice coincided with a fibrotic response as indicated by
      increased collagen and extracellular matrix deposition and increased passive
      mechanical properties of muscle bundles. Overall, our data demonstrate that
      nesprin 1 and desmin serve redundant roles in nuclear anchorage and that the loss
      of nuclear anchorage in skeletal muscle results in a pathological response
      characterized by increased tissue fibrosis and mechanical stiffness. 

PMID- 24943591
TI  - Linking the genetic architecture of cytosine modifications with human complex
      traits.
AB  - Interindividual variation in cytosine modifications could contribute to
      heterogeneity in disease risks and other complex traits. We assessed the genetic
      architecture of cytosine modifications at 283,540 CpG sites in lymphoblastoid
      cell lines (LCLs) derived from independent samples of European and African
      descent. Our study suggests that cytosine modification variation was primarily
      controlled in local by single major modification quantitative trait locus (mQTL)
      and additional minor loci. Local genetic epistasis was detectable for a small
      proportion of CpG sites, which were enriched by more than 9-fold for CpG sites
      mapped to population-specific mQTL. Genetically dependent CpG sites whose
      modification levels negatively (repressive sites) or positively (facilitative
      sites) correlated with gene expression levels significantly co-localized with
      transcription factor binding, with the repressive sites predominantly associated
      with active promoters whereas the facilitative sites rarely at active promoters.
      Genetically independent repressive or facilitative sites preferentially modulated
      gene expression variation by influencing local chromatin accessibility, with the
      facilitative sites primarily antagonizing H3K27me3 and H3K9me3 deposition. In
      comparison with expression quantitative trait loci (eQTL), mQTL detected from
      LCLs were enriched in associations for a broader range of disease categories
      including chronic inflammatory, autoimmune and psychiatric disorders, suggesting
      that cytosine modification variation, while possesses a degree of cell linage
      specificity, is more stably inherited over development than gene expression
      variation. About 11% of unique single-nucleotide polymorphisms reported in the
      Genome-Wide Association Study Catalog were annotated, 78% as mQTL and 31% as eQTL
      in LCLs, which covered 37% of the investigated diseases/traits and provided
      insights to the biological mechanisms.

PMID- 24943592
TI  - Excess of homozygosity in the major histocompatibility complex in schizophrenia.
AB  - Genome-wide association studies (GWAS) in schizophrenia have focused on additive
      allelic effects to identify disease risk loci. In order to examine potential
      recessive effects, we applied a novel approach to identify regions of excess
      homozygosity in an ethnically homogenous cohort: 904 schizophrenia cases and 1640
      controls drawn from the Ashkenazi Jewish (AJ) population. Genome-wide examination
      of runs of homozygosity identified an excess in cases localized to the major
      histocompatibility complex (MHC). To refine this signal, we used the recently
      developed GERMLINE algorithm to identify chromosomal segments shared identical-by
      descent (IBD) and compared homozygosity at such segments in cases and controls.
      We found a significant excess of homozygosity in schizophrenia cases compared
      with controls in the MHC (P-value = 0.003). An independent replication cohort of
      548 schizophrenia cases from Japan and 542 matched healthy controls demonstrated
      similar effects. The strongest case-control recessive effects (P = 8.81 * 10(-8))
      were localized to a 53-kb region near HLA-A, in a segment encompassing three
      poorly annotated genes, TRIM10, TRIM15 and TRIM40. At the same time, an adjacent
      segment in the Class I MHC demonstrated clear additive effects on schizophrenia
      risk, demonstrating the complexity of association in the MHC and the ability of
      our IBD approach to refine localization of broad signals derived from
      conventional GWAS. In sum, homozygosity in the classical MHC region appears to
      convey significant risk for schizophrenia, consistent with the ecological
      literature suggesting that homozygosity at the MHC locus may be associated with
      vulnerability to disease. 

PMID- 24943593
TI  - Pathway-based analysis of GWAs data identifies association of sex determination
      genes with susceptibility to testicular germ cell tumors.
AB  - Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have
      identified 18 susceptibility loci, some containing genes encoding proteins
      important in male germ cell development. Deletions of one of these genes, DMRT1,
      lead to male-to-female sex reversal and are associated with development of
      gonadoblastoma. To further explore genetic association with TGCT, we undertook a
      pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT
      cases and 919 controls). We analyzed a custom-built sex determination gene set
      consisting of 32 genes using three different methods of pathway-based analysis.
      The sex determination gene set ranked highly compared with canonical gene sets,
      and it was associated with TGCT (FDRG = 2.28 * 10(-5), FDRM = 0.014 and FDRI =
      0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of
      Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for
      Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The
      association remained after removal of DMRT1 from the gene set (FDRG = 0.0002,
      FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases
      and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated
      these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG =
      1.04 * 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene
      set, the sex determination gene set remains associated with TGCT in the NCI (FDRG
      = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 * 10(-5), FDRM
      = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex
      determination gene set have not previously been identified as TGCT susceptibility
      loci in these GWA scans, demonstrating the complementary nature of a pathway
      based approach for genome-wide analysis of TGCT. 

PMID- 24943596
TI  - Meschiidae, a new family of Lygaeoidea (Hemiptera: Heteroptera) from India and
      Australia, with descriptions of a new genus and two new species .
AB  - Meschiidae fam. nov. is erected for the genera Meschia Distant, 1910, containing
      four species: M. pugnax Distant, 1910 and M. quadrimaculata Distant, 1910 from
      India, M. woodwardi Scudder, 1957 from Queensland, Australia, and M. barrowensis
      sp. nov. from Barrow Island, Western Australia, and the related Neomeschia gen.
      nov. with type species N. queenslandensis sp. nov. from Queensland, Australia. A
      key to all Australian species and genera is provided. Redescriptions are provided
      for Meschia, its type species M. pugnax, and M. woodwardi. Relationships, and
      reasons for the new family placement of Meschia, are discussed. 

PMID- 24943597
TI  - Review of the Philippine taxa formerly assigned to the genus Amphicnemis Selys,
      II. Genus Sangabasis with descriptions of eight new species (Odonata:
      Coenagrionidae).
AB  - The Philippine genus Sangabasis Villanueva is reviewed. Eight new species are
      described: S. bukid sp. nov., S. bulba sp. nov., S. cahilogi sp. nov., S.
      carmelae sp. nov., S. feliculoi sp. nov., S. hamis sp. nov., S. janvantoli sp.
      nov., and S. zamboanga sp. nov. 

PMID- 24943598
TI  - Complete larval development of the Brachyuran crab (Epixanthus Frontalis H. Milne
      Edwards, 1834) (Crustacea, Decapoda, Eriphioidea, Oziidae) under laboratory
      conditions.
AB  - The complete larval development of the oziid crab Epixanthus frontalis (H. Milne
      Edwards, 1834) hatched from ovigerous specimens collected from Saso Island,
      southern Red Sea, was obtained under laboratory conditions. Four zoeae, one
      additional zoea and a megalopa were obtained and these are described and
      illustrated in detail for the first time. Larvae of this species can be
      differentiated from those of other oziid species based on a combination of
      characters such as the number of aesthetascs and setae of the antennule, and the
      coxal and basial setal numbers and patterns of the maxilla and maxillule. 

PMID- 24943595
TI  - Most common 'sporadic' cancers have a significant germline genetic component.
AB  - Common cancers have been demarcated into 'hereditary' or 'sporadic' ('non
      hereditary') types historically. Such distinctions initially arose from work
      identifying rare, highly penetrant germline mutations causing 'hereditary'
      cancer. While rare mutations are important in particular families, most cases in
      the general population are 'sporadic'. Twin studies have suggested that many
      'sporadic' cancers show little or no heritability. To quantify the role of
      germline mutations in cancer susceptibility, we applied a method for estimating
      the importance of common genetic variants (array heritability, h(2)g) to twelve
      cancer types. The following cancers showed a significant (P < 0.05) array
      heritability: melanoma USA set h(2)g = 0.19 (95% CI = 0.01-0.37) and Australian
      set h(2)g = 0.30 (0.10-0.50); pancreatic h(2)g = 0.18 (0.06-0.30); prostate h(2)g
      = 0.81 (0.32-1); kidney h(2)g = 0.18 (0.04-0.32); ovarian h(2)g = 0.30 (0.18
      0.42); esophageal adenocarcinoma h(2)g = 0.24 (0.14-0.34); esophageal squamous
      cell carcinoma h(2)g = 0.19 (0.07-0.31); endometrial UK set h(2)g = 0.23 (0.01
      0.45) and Australian set h(2)g = 0.39 (0.02-0.76). Three cancers showed a
      positive but non-significant effect: breast h(2) g = 0.13 (0-0.56); gastric h(2)g
      = 0.11 (0-0.27); lung h(2)g = 0.10 (0-0.24). One cancer showed a small effect:
      bladder h(2)g = 0.01 (0-0.11). Among these cancers, previous twin studies were
      only able to show heritability for prostate and breast cancer, but we can now
      make much stronger statements for several common cancers which emphasize the
      important role of genetic variants in cancer susceptibility. We have demonstrated
      that several 'sporadic' cancers have a significant inherited component. Larger
      genome-wide association studies in these cancers will continue to find more loci,
      which explain part of the remaining polygenic component.

PMID- 24943599
TI  - A diminutive new species of cave-dwelling Wolf Snake (Colubridae: Lycodon Boie,
      1826) from Peninsular Malaysia.
AB  - A newly discovered, diminutive, cave-dwelling, lowland species of the colubrid
      snake genus Lycodon Boie is described from a limestone cave along the Thai
      Malaysian border in the state of Perlis, northwestern Peninsular Malaysia.
      Lycodon cavernicolus sp. nov. is most closely related to L. butleri Boulenger, an
      endemic, upland, forest-dwelling species from Peninsular Malaysia of the
      fasciatus group but is separated from L. butleri and all other species of the L.
      fasciatus group and the closely related L. ruhstrati group by having the
      combination of 245 (male) and 232 (female) ventral scales; 113 (male) and 92
      (female) paired, subcaudal scales; a single precloacal plate; nine or 10
      supralabials; 10 or 11 infralabials; a maximum total length of 508 mm (female); a
      relative tail length of 0.25-0.27; an immaculate venter in juveniles and dark
      brown, posterior, ventral scale margins in adults; and dorsal and caudal bands in
      juveniles white. The discovery of L. cavernicolus sp. nov. adds to a rapidly
      growing list of newly discovered reptiles from karst regions and limestone
      forests of Peninsular Malaysia, underscoring the fact that these areas should be
      studied before they are quarried as they harbor a significant portion of the
      Peninsular Malaysia's herpetological diversity. 

PMID- 24943600
TI  - New species of Rhamphomyia (Diptera: Empididae) from Turkey with a key to species
      of the Middle East and adjacent territories.
AB  - Rhamphomyia (s. str.) academica sp. nov. (Turkey) and R. (s. str.) soukupi sp.
      nov. (Turkey) are described and illustrated. Rhamphomyia (Lundstroemiella)
      cimrmani Bartak, 2006, is re-described and the female is newly described. The
      first records of Rhamphomyia (s. str.) argentata von Roder, 1887 and R.
      (Pararhamphomyia) intersita Collin, 1960 are reported from Turkey. A key to
      species of Rhamphomyia from the Middle East is presented. 

PMID- 24943601
TI  - The huntsman genus Decaphora Franganillo, 1931 (Araneae: Sparassidae:
      Sparianthinae).
AB  - The genus Decaphora Franganillo, 1931 is revised. Pseudosparianthis variabilis
      F.O. Pickard-Cambridge, 1900, Pseudosparianthis cubana Banks, 1909 and
      Thelcticopis pestai (Reimoser, 1939) are transferred to the genus; and P. cubana
      is considered a senior synonym of the type species, Decaphora trabiformis
      Franganillo, 1931. In addition, the female of T. pestai and the male of P.
      variabilis are described for the first time; and a new species, Decaphora
      kohunlich spec. nov., is described from Mexico and Guatemala. 

PMID- 24943602
TI  - Cebudonus poppeorum, a new genus and new species of eumedonine crab (Crustacea:
      Decapoda: Brachyura: Pilumnidae) from the Philippines.
AB  - A new genus and new species of eumedonine crab, Cebudonus poppeorum, is described
      from the central Philippines. Superficially similar to Eumedonus H. Milne
      Edwards, 1834, Gonatonotus White, 1847, Zebrida White, 1847, Zebridonus Chia, Ng
      & Castro, 1995, and Tiaramedon Chia & Ng, 1998, Cebudonus n. gen. is easily
      characterised by possessing two long pseudorostral spines, a gently convex and
      unarmed dorsal carapace surface, elongated chelipeds that have the chela and
      merus unarmed and not cristate, elongated and slender ambulatory legs in which
      the merus is not cristate, a relatively narrow anterior male thoracic sternum,
      and a proportionately broader male abdomen. The general structure and colour
      pattern (with longitudinal stripes) suggests Cebudonus n. gen. is an obligate
      symbiont with echinoids. 

PMID- 24943603
TI  - Taxonomic study of Central Asian species of the genus Macropsis Lewis, 1836
      (Homoptera: Auchenorrhyncha: Cicadellidae: Macropsinae). II: redescriptions of
      poorly known species, new synonyms, and description of a new willow-dwelling
      species.
AB  - Macropsis validiuscula Dubovsky, 1966, M. vicina (Horvath, 1897) = M. populicola
      Dubovsky, 1966 = M. albinata Dubovsky, 1966, syn. n. = M. albidula Dubovsky,
      1966, syn. n., M. iliensis Mityaev, 1971 and M. elaeagnicola Dubovsky, 1966 are
      redescribed and illustrated based on material from Tien Shan Mts. (Kyrgyzstan)
      and Ferghana Valley (Uzbekistan), M. tienschanica Tishetshkin sp. n. from West
      Tien Shan Mts. (Kyrgyzstan) is described. M. iliensis Mityaev, 1971 is recorded
      from Kyrgyzstan for the first time. Data on host plants and male vibrational
      calling signals for all species considered are provided. 

PMID- 24943604
TI  - Two new species of Lasiopa (Diptera, Stratiomyidae) from Turkey.
AB  - Two new species, Lasiopa aksarayiensis sp. n. and Lasiopa aktasii sp. n. are
      described from the Central Anatolian stepe in Turkey. All diagnostic characters
      are illustrated and possible relationships of both taxa are briefly discussed.
      The first record of Lasiopa pseudovillosa (Rozkosny, 1983) from Turkey is
      presented and additional Turkish localities of Lasiopa caucasica (Pleske, 1901)
      are recorded and an identification key to all the Palaearctic species of Lasiopa
      is given. 

PMID- 24943605
TI  - A new species of the pontoniine shrimp genus Hamopontonia Bruce, 1970 associated
      with caryophyllid coral Euphyllia glabrescens (Chamisso & Eysenhardt, 1821) in
      Nhatrang Bay, Vietnam.
AB  - Hamopontonia nhatrangensis sp. nov. (Crustacea, Decapoda, Palaemonidae,
      Pontoniinae) is described from Nhatrang Bay, Vietnam, in association with
      caryophyllid coral Euphyllia glabrescens (Chamisso & Eysenhardt, 1821)
      (Hexacorallia, Scleractinia, Caryophyllidae). The new species clearly differs
      from congeners by morphological features, distinctive coloration and
      ecologically. Renewed differential key to all known species of the genus
      Hamopontonia Bruce, 1970 is provided.  

PMID- 24943606
TI  - A new species of Altipolia (Lepidoptera: Noctuidae, Xyleninae) from China.

PMID- 24943607
TI  - The advertisement call of the endemic Bokermannohyla martinsi (Bokermann, 1964)
      (Anura: Hylidae) from southern Espinhaco range, southeastern Brazil.

PMID- 24943608
TI  - The phallus in Tettigoniidae (Insecta: Orthoptera: Ensifera): revision of
      morphology and terminology, and discussion on its taxonomic importance and
      evolution.
AB  - The phallus in Tettigoniidae (katydids) is a structure informative relative to
      the systematics of the group. Despite this, it is often not considered in
      descriptions of taxa. The lack of adequate descriptions of phalli is not only a
      gap for sytematic and morphological studies, but postpones works on the evolution
      of copula. Here we study the exoskeletal morphology of the phallus in katydids,
      its components, and revised the terminology for them. We carried out dissections
      for morphological comparisons, and complement the observational information with
      published data. We stained phalli of katydids with chlorazol black, to better
      contrast membranous versus sclerotized components. We demonstrate that phallic
      components vary at specific, generic and suprageneric levels, and that internal
      and external components vary in number, shape, size and position. Currently there
      is little comparative data to support hypotheses on the evolution of this
      structure, but possibly the possession of a titillator is an ancestral condition.
      We identify additional sclerotized components, the sclerites of the ventral fold
      of the dorsal lobe, which can modify the shape and function of the titillator,
      being also important for understanding the evolution of the phallus. Potential
      functional relationships based on hypothetical morphological correlations between
      the shape of titillator and cerci are proposed, categorized in three main groups:
      (i) phallus devoid of titillator and cerci simple, (ii) titillator with
      bifurcated or paired sclerites, and cerci adapted for grasping, and (iii)
      titillator with single process and/or sclerite and cerci simple, sometimes with a
      pointed tip. Two explanations for these hypothetical morphological correlations
      and morphological variation are proposed: first, species with similar structures
      at the postabdomen would share similar copulatory behaviour, and second, more
      than one selective pressure would have acted over the structures of the
      postabdomen.

PMID- 24943609
TI  - A new troglobiotic species of Hyalella (Crustacea, Amphipoda, Hyalellidae) with a
      taxonomic key for the Brazilian species.
AB  - The freshwater crustaceans from the order Amphipoda occur mainly in cold and
      temperate climates. However, in the tropics, these animals can be more abundant
      in subterranean environments, where the temperatures are milder than in surface.
      Despite being accepted that the number of species of freshwater amphipods in
      South America is lower when compared to other regions, recent descriptions have
      shown that its diversity is certainly underestimated. In this study, a new
      species of the genus Hyalella is described for Brazil, the fourth troglobiotic
      species of Hyalella for the country and the sixth in the world. The new species
      was found on the epikarst of a cave in Sao Paulo state, Southeastern Brazil.
      Besides, the new species shows typical characteristics from organisms adapted to
      the subterranean environments, a pattern also observed in the other troglobiotic
      species of the genus. 

PMID- 24943610
TI  - Taxonomic notes on some Brazilian species of Synalpheus Spence Bate, 1888, with
      new records and description of a new species (Decapoda, Alpheidae).
AB  - The present report deals with several western Atlantic species of the snapping
      shrimp genus Synalpheus Spence Bate, 1888 occurring in Brazilian territorial
      waters. Two species, Synalpheus cf. ruetzleri Macdonald & Duffy, 2006 and
      Synalpheus yano (Rios & Duffy, 2007), are recorded from the southwestern Atlantic
      Ocean and Brazil (Ceara) for the first time; S. yano is also newly reported from
      the eastern Gulf of Mexico and USA (Florida). Synalpheus androsi Coutiere, 1909,
      a distinctive species previously known in Brazil only from a single unconfirmed
      record, is confirmed to be present in Brazilian waters based on material from
      Bahia and Espirito Santo. Synalpheus tenuispina Coutiere, 1909, a poorly known
      species from southern Brazil, is redescribed. Synalpheus ul (Rios & Duffy, 2007),
      previously known from Bahia and Alagoas, is reported from Pernambuco based on
      older "Calypso" material misidentified as Synalpheus longicarpus (Herrick, 1891).
      A new species from the Synalpheus paraneptunus Coutiere, 1909 complex is
      described as Synalpheus maxillispinus sp. nov. based on three specimens dredged
      from moderate depths (15-55 m) off southern Bahia and Espirito Santo, eastern
      Brazil. Finally, an incomplete specimen that appears to belong to a species
      presently unknown in Brazil is preliminarily reported as Synalpheus sp.
      gambarelloides group. Illustrations are provided for all reported taxa except for
      S. ul. 

PMID- 24943611
TI  - Mucha Ozerov and Ortalischema Frey newly recorded from China with descriptions of
      two new species (Diptera, Sepsidae).
AB  - Eleven genera and 55 species of Sepsidae were known to occur in China. Here two
      genera, Mucha Ozerov and Ortalischema Frey, are newly reported from China with
      the following two new species: Mucha liangi sp. nov. and M. yunnanensis sp. nov.
      Two species, Mucha tzokotucha and Ortalischema maritima, are newly recorded from
      China. Thus, there are a total of 13 genera of Sepsidae distributed in China. A
      key to the species of Mucha and a key to the Chinese genera of Sepsidae are
      provided. 

PMID- 24943612
TI  - Two new species and two new records of deep-water caridean shrimps from Brazil
      (Decapoda: Pandalidae, Palaemonidae, Crangonidae).
AB  - The present study deals with four species of benthic deep-water caridean shrimps
      collected on the continental slope off southeastern Brazil, between 360 m and 900
      m. The deepwater pandalid Bitias stocki Fransen, 1990, previously known only from
      a few localities in the eastern Atlantic, is reported for the first time from the
      western Atlantic (Brazil). The Brazilian material of B. stocki also represents
      the first record of the genus Bitias Fransen, 1990 in the western Atlantic. The
      palaemonid Periclimenes tenellus (Smith, 1882), previously known only from South
      Carolina and New Jersey, USA, is reported for the first time from Brazil,
      representing a considerable range extension of this uncommon species into the
      southwestern Atlantic. Another deepwater palaemonid shrimp is described as new:
      Periclimenes bathyalis sp. nov. The new species is morphologically closest to the
      echinoid associates Periclimenes milleri Bruce, 1986 and Periclimenes
      ingressicolumbi Berggren & Svane, 1989. Finally, the bizarre deepwater crangonid
      genus Prionocrangon Wood-Mason in Wood-Mason & Alcock, 1891 is reported for the
      first time from Brazil and the southwestern Atlantic, where it is represented by
      a new species, Prionocrangon brasiliensis sp. nov. 

PMID- 24943613
TI  - Two new species of Tetralidia Marques-Costa & Cavichioli (Hemiptera:
      Cicadellidae: Neocoelidiinae) from Peru with a key to species of the genus.
AB  - Two new species of Tetralidia Marques-Costa & Cavichioli, 2008: Tetralidia
      pachamama sp. nov. and Tetralidia viracocha sp. nov. are described and
      illustrated. T. pachamama sp. nov. can be distinguished from the other species of
      the genus by the simple aedeagus, without processes, spines or lamellae, while T.
      viracocha sp. nov. can be distinguished by the aedeagus with two pairs of
      lamellae at shaft and anal tube with basiventral processes strongly curved
      posteriorly. An identification key to males of the species is provided. 

PMID- 24943614
TI  - A new species of the genus Crepidodera Chevrolat (Coleoptera: Chrysomelidae) from
      Baltic amber.
AB  - A new flea-beetle species, Crepidodera svetlanae sp. nov. (Coleoptera:
      Chrysomelidae: Galerucinae: Alticini) is described and illustrated from the
      Baltic amber. The new species is compared with the fossil and recent species of
      the genus. A key to species of flea beetles known from fossil resin is provided. 

PMID- 24943616
TI  - Nomenclatural corrections to two Neotropical species of Staphylininae
      (Coleoptera: Staphylinidae).

PMID- 24943615
TI  - A redefinition of the genus Hemichaeta Steyskal, new status (Diptera;
      Micropezidae; Taeniapterinae).
AB  - We here reconsider the status of subgenus Hemichaeta Steyskal, concluding that
      there is no justification to keep it in the genus Poecilotylus Hennig. Hemichaeta
      is thus removed from Poecilotylus and elevated to generic status with Hemichaeta
      scutellata (Cresson) as the type and only included species. Hemichaeta scutellata
      is fully redescribed, including the previously undescribed male and female
      terminalia. 

PMID- 24943617
TI  - Starostinia, a new generic replacement name for Ironella Starostina & Krasnov,
      1970 (Anthozoa: Scleractinia: Rhipidogyridae) non Cobb, 1920 (Nematoda:
      Ironidae).

PMID- 24943619
TI  - Keys to the species of Athesmia Loss, 1899 (Digenea: Dicrocoeliidae:
      Dicrocoeliinae), with the description of a new species from the clapper rail,
      Rallus longirostris Boddaert (Gruiformes: Rallidae), from Galveston, Texas,
      U.S.A.
AB  - Eleven specimens of a previously undescribed species of Athesmia Looss, 1899 were
      recovered from six clapper rails, Rallus longirostris Boddaert (Rallidae),
      collected from November, 1984 through October, 1995 from the Galveston, Texas
      area of the Gulf of Mexico. Species of Athesmia can be divided into two body
      types based on the posterior extent of the ceca relative to the vitelline field
      (vitellarium): the attilae type where the ceca may be uneven, but they both
      extend at least to near the level of the posterior margin of the vitelline field,
      or more commonly surpass the vitelline field posteriorly and the
      heterolechithodes type where the cecum on the side of the vitelline field
      terminates well above the posterior margin of the vitelline field, usually near
      its anterior extremity, while the cecum opposite the vitelline field extends at
      least to the level of the posterior margin of the vitelline field, or more
      commonly surpasses the vitelline field posteriorly. Athesmia ralli n. sp. is
      assigned to the attilae type. The new species is most similar to Athesmia
      butensis Petri, 1942, but differs from this species by having a longer space from
      posterior testis to ovary (600-790 compared to less than 200), which represent a
      larger percentage of the total body length (7-8% compared to 2%) and a larger
      maximum egg size (47 by 29 compared to 42 by 25). The new species further differs
      from A. butensis by having a somewhat larger body, a longer forebody and the
      vitelline field reaches posteriorly to the posterior third of the body in the new
      species but is confined to the middle third of the body in A. butensis. A key to
      species also is provided. 

PMID- 24943618
TI  - Deep-sea Bodotriidae, Diastylidae and Pseudocumatidae (Cumacea, Crustacea) from
      the southeastern Atlantic.
AB  - Nine species of the family Diastylidae, two species of the family Bodotriidae and
      one species of the family Pseudocumatidae are present in the Diva II and Ifremer
      collections. Two new species were recognized and described herein. However, one
      of the new species has to remain in open nomenclature due to its young
      developmental stage. The new species are Makrokylindrus (Makrokylindrus)
      abyssalis, and M. (Adiastylis) sp.1. The distribution range is enlarged based on
      the new findings for seven species. 

PMID- 24943620
TI  - Revision of Silhouettanus with description of nine new species (Hemiptera:
      Heteroptera: Schizopteridae).
AB  - The description of Silhouettanus alboclavatus Emsley, 1969 (Hemiptera:
      Schizopteridae) is recognized, supplemented and nine new species of Silhouettanus
      Emsley, 1969 (Hemiptera: Schizopteridae) are described from Queensland and New
      Caledonia. They are S. bamaganus sp. n., S. insulomagnus sp. n., S. insuloparvus
      sp. n., S. lintrarius sp. n., S. magnus sp. n., S. monteithi sp. n., S. pilosus
      sp. n., S. tinnulus sp. n. and S. turbator sp. n. A key to males of the species
      is provided. Notes on two undescribed Australian genera also with porrect heads
      and the holotype of Dictyonannus flavus Gross, 1951 are given. Morphological
      comparisons with other schizopterid genera are given. 

PMID- 24943621
TI  - A new species of Abyssocladia (Porifera, Demospongiae, Poecilosclerida,
      Cladorhizidae) and other carnivorous sponges from the far eastern Solomon
      Islands.
AB  - Two species, one each of Abyssocladia Levi, 1964, and Asbestopluma Topsent, 1901,
      are recorded from the far eastern Solomon Islands for the first time.
      Abyssocladia lakwollii sp. nov. is characterized by the pedunculate disc-shape of
      the body, the unusually large size of the isochelae I microscleres, and by the
      shape of the cleistochelae with crossed central teeth. Asbestopluma (A.)
      desmophora Kelly & Vacelet, 2011, first described from a seamount on Macquarie
      Ridge (Australia EEZ) and eastern waters to the north and south of New Zealand,
      is also recorded from the far eastern Solomon Islands. The specimens differ only
      slightly from their southern counterparts in dimensions of some spicules, and in
      the ornamentation detail of the basal teeth of the large and small anisochelae.  

PMID- 24943622
TI  - The genus Labiobaetis (Ephemeroptera: Baetidae) in China, with description of a
      new species.
AB  - Five species of the genus Labiobaetis (Baetidae) are recognized from China based
      on mature nymphs, including a new species, Labiobaetis ancoralis n. sp. and a new
      combination, Labiobaetis mustus (Kang & Yang) n. comb. The new species differs
      from L. multus (Muller-Liebenau) and L. pulchellus (Muller-Liebenau & Hubbard) by
      the spatulate submarginal setae on labrum and the apical segment of maxillary
      palpus with a pronounced excavation near apex. Imago stage of L. mustus (Kang &
      Yang) n. comb. is described for the first time based on male and female imagoes
      reared from nymphs, which can be distinguished from other known imagoes of
      Labiobaetis by the color pattern of abdominal terga and hind wing having a tiny
      vestigial costal process. All Oriental species previously transferred to
      Pseudocloeon are reassigned to Labiobaetis in the present paper. An
      identification key is provided to the known mature nymphs of Oriental Labiobaetis
      species. 

PMID- 24943623
TI  - Two new species of Chrysotus Meigen (Diptera, Dolichopodidae) from Siberia, with
      a key to the Siberian species.
AB  - Two new species from the southern tundra of the Taimyr Peninsula (Russia) are
      described. Chrysotus tricaudatus Negrobov, Barkalov & Selivanova sp. nov. is
      similar to C. albibarbus Loew, but can be distinguished by its brown palpus with
      black setae, yellow hind tibia and base of hind tarsus, and features of the male
      genitalia. Chrysotus komovi Negrobov, Barkalov & Selivanova sp. nov. is similar
      to C. obscuripes Zetterstedt, but can be distinguished by features of the male
      genitalia. A key to all Siberian species of the genus is also presented along
      with figures of diagnostic morphological characters.  

PMID- 24943624
TI  - Nemozoma gymnosternalis sp. nov., a new anomalous species of Trogossitidae from
      Brazil.
AB  - Nemozoma gymnosternalis sp. nov., a new member of the tribe Trogossitini
      (Trogossitidae) from southeastern Brazil is described. The species is distinct in
      its morphological characters, namely the shortened elytra, abdominal tergites
      enwound with projected folds of ventrites, and modified structure of extremely
      shortened ovipositor. Leveille's assignment of Airora quadrimaculatus Leveille,
      1894 to the genus Corticotomus Sharp, 1891 is confirmed. The systematics of
      brachelytric species of Nemozoma Latreille, 1804 is briefly discussed. The
      presence of two projecting cranial horns, a structure that occurs in several
      unrelated beetle groups with a similar biology, is also mentioned.  

PMID- 24943625
TI  - Description of the larva of Philopotamus achemenus Schmid 1959 (Trichoptera:
      Philopotamidae) and a larval key for species of Philopotamus in Greece.
AB  - The larva of Philopotamus achemenus is described for the first time. The
      diagnostic features of the species are described and illustrated and some
      information regarding its ecology and world distribution is included.
      Furthermore, its morphological characters are compared and contrasted in an
      identification key for larvae of the Greek species of Philopotamus.  

PMID- 24943626
TI  - New species and new record of Megatyrus Hlavac & Nomura (Coleoptera:
      Staphylinidae: Pselaphinae) from Asia.
AB  - A new species, Megatyrus femoralis sp. n., is described from the Koshi Zone, East
      Nepal, with major diagnostic features illustrated. Megatyrus masumotoi Nomura,
      Sakchoowong & Chanpaisaeng, originally described from southwestern Thailand, is
      recorded from the Noring Timur Mountain, West Malaysia. The above data extends
      the known range of Megatyrus about 1,200 km to the west, and 870 km to the south.

PMID- 24943594
TI  - Common non-synonymous SNPs associated with breast cancer susceptibility: findings
      from the Breast Cancer Association Consortium.
AB  - Candidate variant association studies have been largely unsuccessful in
      identifying common breast cancer susceptibility variants, although most studies
      have been underpowered to detect associations of a realistic magnitude. We
      assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for
      which evidence of association with breast cancer risk had been previously
      reported. Case-control data were combined from 38 studies of white European women
      (46 450 cases and 42 600 controls) and analyzed using unconditional logistic
      regression. Strong evidence of association was observed for three nsSNPs: ATXN7
      K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) =
      1.04-1.10, P = 2.9 * 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI =
      1.03-1.07, P = 1.7 * 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95%
      CI = 1.07-1.12, P = 5.1 * 10(-17)). The first two associations reached genome
      wide statistical significance in a combined analysis of available data, including
      independent data from nine genome-wide association studies (GWASs): for ATXN7
      K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 * 10(-8)); for AKAP9-M463I, OR =
      1.05 (95% CI = 1.04-1.07, P = 2.0 * 10(-10)). Further analysis of other common
      variants in these two regions suggested that intronic SNPs nearby are more
      strongly associated with disease risk. We have thus identified a novel
      susceptibility locus at 3p21, and confirmed previous suggestive evidence that
      rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is
      located in an established breast cancer susceptibility region; the association
      was substantially attenuated after adjustment for the known GWAS hit. Thus, each
      of the associated nsSNPs is likely to be a marker for another, non-coding,
      variant causally related to breast cancer risk. Further fine-mapping and
      functional studies are required to identify the underlying risk-modifying
      variants and the genes through which they act. 

PMID- 24943627
TI  - A new Munidopsis species (Galatheoidea, Munidopsidae) from the Southwestern
      Atlantic.
AB  - Six Munidopsis species are recorded to the Southwestern Atlantic: M. barbarae; M.
      erinacea; M. nitida; M. sigsbei; M. riveroi and M. transtridens. Herein a new
      Munidopsis species from Southwestern Atlantic is described: Munidopsis
      trindadensis sp.nov., was sampled off Trindade Island (Espirito Santo, Brazil) at
      360 m depth and differs from all six species previously recorded in this region
      by the telson with seven plates. 

PMID- 24943628
TI  - First description of the male of Diaea mikhailovi (Araneae: Thomisidae).

PMID- 24943629
TI  - Taxonomic revision of the species group rubripes of Corinna Koch, 1842 (Araneae;
      Corinnidae).
AB  - The species of the group rubripes, which harbors the type species of the genus
      Corinna C. L. Koch, 1842, are revised, including 20 Neotropical species. Three
      previously known species are re-diagnosed: Corinna rubripes C. L. Koch, 1842,
      Corinna nitens (Keyserling, 1891) and Corinna mourai Bonaldo, 2000. New records
      of Corinna nitens are provided, including the first ones from Peru and Bolivia.
      Seventeen new species, all from Brazil, were described: C. aechmea n. sp., C.
      balacobaco n. sp., C. caatinga n. sp., C. demersa n. sp., C. escalvada n. sp., C.
      hyalina n. sp., C. jecatatu n. sp., C. kuryi n. sp., C. loiolai n. sp., C.
      maracas n. sp., C. regii n. sp., C. telecoteco n. sp., C. tranquilla n. sp., C.
      vesperata n. sp., C. vilanovae n. sp., C. zecarioca n. sp. and C. ziriguidum n.
      sp. A key for all twenty species of the group is presented. 

PMID- 24943630
TI  - A new species of gecko of the genus Cnemaspis Strauch, 1887 from the Western
      Ghats, India.
AB  - A new species of the gekkonid genus Cnemaspis is described from the lateritic
      plateau of the northern Western Ghats of Maharashtra, western India. The new
      species is diagnosed by the following suite of characters: small sized Cnemaspis,
      SVL less than 35 mm (21.52-33.65). Dorsal scales on trunk heterogeneous, granular
      scales intermixed with large smooth scales and large keeled conical tubercles.
      Spine-like tubercles absent on flank. Two pairs of postmentals, inner postmentals
      separated by a single enlarged chin shield. Ventral scales on trunk smooth,
      imbricate, 26-28 scales across the belly between the lowest rows of dorsal
      scales. Subdigital scansors smooth, entire, unnotched; lamellae under digit IV of
      pes 17-20.Males with four femoral pores on each thigh and lacking pre-cloacal
      pores. Median row of sub-caudals smooth, imbricate and not enlarged. The present
      discovery highlights the need for dedicated herpetofaunal explorations in the
      northern Western Ghats to ascertain the exact diversity and distribution of
      Cnemaspis in India to elucidate the apparent disjunct distribution of the genus
      in the country. 

PMID- 24943631
TI  - The missing leopard lizard: Liolaemus ubaghsi sp. nov., a new species of the
      leopardinus clade (Reptilia: Squamata: Liolaemidae) from the Andes of the
      O'Higgins Region in Chile.
AB  - Liolaemus is an extremely species rich genus of iguanid lizards from southern
      South America. Most of the diversity though is found in the Andes Cordillera,
      between Argentina and Chile<a
      href="http://dx.doi.org/10.11646/zootaxa.3619.1.3">. Here we describe
      </a>Liolaemus ubaghsi sp. nov., from El Teniente Mine, in the Andean mountains of
      the O'Higgins Region in Chile. This species pr<a
      href="http://dx.doi.org/10.1080/10635150701701083">esents scalation </a>and
      pattern traits that belong to the leopardinus clade, a group of viviparous, high
      altitude lizards that inhabit the mountain ranges surrounding Santiago City. The
      species of this clade in turn belong to the Andean and Patagonian elongatus
      kriegi complex. Liolaemus ubaghsi sp. nov. has been previously recognized as L.
      leopardinus and L. elongatus, nevertheless we present diagnostic traits that
      allow us to describe it as a new species. It mainly differs from the rest of the
      leopardinus clade (L. leopardinus, L. ramonensis, L. valdesianus and L.
      frassinettii) by having the following unique combination of traits: ochre
      background coloration, a wide dark occipital stripe, dark flanks, white dots
      dispersed on the dorsum, absence of leopard-like spots and enlarged infralabial
      scales.  

PMID- 24943632
TI  - New Mycomya species from South-East Asia (Diptera, Mycetophilidae) .
AB  - Mycomya Rondani specimens from the islands of South-East Asia, i.e. Malaysia,
      Indonesia and the Philippines, are revised. The paper includes a key to the
      Mycomya species of the South-East Asian islands. The following six new species
      are described: M. shimai sp. n. from Java, Indonesia, M. pongo sp. n. from Sabah,
      Malaysia, and M. apoensis sp. n., M. nakanishii sp. n., M. paraklossi sp. n. and
      M. yatai sp. n. from Mindanao, the Philippines. The holotypes of M. klossi
      Edwards from Borneo, Malaysia, and M. minutata Edwards from Sumatra, Indonesia,
      were examined and their genitalia are described. M. occultans (Winnertz) is
      recorded from Java, Indonesia. 

PMID- 24943633
TI  - Convergent evolution of aquatic foraging in a new genus and species (Rodentia:
      Muridae) from Sulawesi Island, Indonesia.
AB  - The island of Sulawesi, in Indonesia, lies at the crossroads of the Indo
      Australian Archipelago and has remained isolated from the Asian (Sunda) and
      Australian (Sahul) continental shelves for at least the last 10 million years. Of
      the 50 native species of rodents on Sulawesi, all are endemic and represent the
      evolution of a variety of ecological and morphological forms within the Muridae
      and Sciuridae. Carnivorous rodents have evolved, perhaps independently, in
      Muridae from the Philippines, Sulawesi, and Sahul, but semi-aquatic murids are
      only known from Sahul. Here we describe a new genus and species of insectivorous
      water rat from Sulawesi. Phylogenetic analyses demonstrate that it is related to
      the shrew rats of Sulawesi and represents an origin of aquatic carnivory that is
      independent from the evolution of water rats on Sahul. Many areas of Sulawesi
      have not been surveyed systematically and current lists of mammal species are
      likely to dramatically underestimate actual diversity. 

PMID- 24943634
TI  - Two new species of freshwater crabs of the genus Sundathelphusa Bott, 1969
      (Decapoda: Brachyura: Gecarcinucidae) from caves in Luzon, Philippines.
AB  - Two cave species of Sundathelphusa are described from a karst area in southern
      Luzon, Philippines. Both species have elongated ambulatory legs but the eyes and
      carapace pigmentation are well developed, indicating they are not troglobites.
      Sundathelphusa danae sp. nov. is superficially more similar to S. longipes
      (Balss, 1937) than to S. holthuisi Ng, 2010, which was described from the same
      locality. Sundathelphusa danae sp. nov. is distinguished from its closest
      congeners by its strongly convex anterolateral margin, more swollen branchial
      regions, possession of a complete frontal median triangle, laterally inflated
      subbranchial region and the more slender ambulatory legs. Sundathelphusa vienae
      sp. nov. is unusual among Sundathelphusa species in that its carapace is more
      quadrate, with the slender and almost straight male first gonopod tapered and
      having a pointed terminal segment.  

PMID- 24943635
TI  - A new species of Chaeridiona Baly (Coleoptera: Chrysomelidae: Cassidinae:
      Oncocephalini) infesting ginger Zingiber officinale Roscoe) and turmeric (Curcuma
      longa L.) in India and redescription of Chaeridiona pseudometallica Basu.
AB  - Chaeridiona mayuri n. sp. infesting ginger (Zingiber officinale Roscoe) and
      turmeric (Curcuma longa L.) in southern India is described and illustrated.
      Cheilocostus speciosus ( J. Koenig) C. D. Specht, Globba sessiliflora Sims and
      Zingiber zerumbet (L.) Smith are reported as additional host plants. Chaeridiona
      pseudometallica Basu is redescribed and illustrated. A key to the species of
      Indian Chaeridiona is provided. 

PMID- 24943636
TI  - Description of two new Jujubinus species (Gastropoda: Trochidae) from the Sicily
      Channel, with notes on the Jujubinus curinii species complex.
AB  - Based on shell characters, two new species of the gastropod family Trochidae,
      Jujubinus eleonorae n. sp. and Jujubinus trilloi n. sp., from the Sicily Channel
      are described. Shells of the new taxa were collected in the lower infralittoral
      of the Skerki and Talbot Banks, respectively. The new taxa are compared with
      Jujubinus curinii Bogi & Campani, 2005, morphologically the most closely related
      species. 

PMID- 24943637
TI  - First record of the genus Aplomerus Provancher, 1886 (Hymenoptera: Ichneumonidae:
      Xoridinae) from the Oriental region, with descriptions of two new species.
AB  - The genus Aplomerus Provancher, 1886 (Hymenoptera, Ichneumonidae) is a small
      genus of the subfamily Xoridinae. Two new species from Asia, A. orientalis Varga
      & Reshchikov sp. n. from Thailand and A. phamae Broad sp. n. from Vietnam, are
      described and illustrated. An identification key for Asian species is provided.
      These are the first records of the genus from the Oriental region and increases
      the known number of Aplomerus species to eight, with a disjunct distribution of
      North America, Japan and south-east Asia. 

PMID- 24943639
TI  - Plasma synthesis of stoichiometric Cu2S nanocrystals stabilized by oleylamine.
AB  - Nonthermal plasmas can produce high quality nanocrystals in a continuous process
      without requiring solvents. A nonthermal plasma process is demonstrated to
      synthesize stoichiometric Cu2S nanocrystals, which show no signs of oxidation by
      spectrophotometry after 2 months in the ambient when stabilized with oleylamine
      and dispersed in toluene. 

PMID- 24943641
TI  - Outcomes and their predictors in lumbar spinal stenosis: a 12-year follow-up.
AB  - PURPOSE: The aim of this prospective observational cohort study was to evaluate
      long-term outcomes in patients with mild-to-moderate lumbar spinal stenosis (LSS)
      and to analyse the predictors of clinical outcomes. METHODS: A group of 53
      patients were re-examined after a median period of 139 months. Evaluations were
      made of subjective clinical outcome, objective clinical outcome and its
      predictors, any correlation between subjective and objective outcome, and the
      development of changes in radiological and electrophysiological parameters after
      12 years. RESULTS: Satisfactory objective and subjective clinical outcomes were
      recorded in 54.7 and 43.4% of patients, respectively. No statistically
      significant correlation between objective and subjective clinical outcome was
      found (Spearman coefficient = 0.225, p = 0.132). Patients with isolated
      unsatisfactory subjective outcome exhibited the highest Functional Comorbidity
      Index of all subgroups. Electrophysiological and radiological findings did not
      demonstrate statistically significant changes after 12-year follow-up.
      Multivariate logistic regression confirmed only the lowest transverse diameter of
      spinal canal ?13.6 mm as an independent predictor of unsatisfactory clinical
      outcome (OR = 5.51). CONCLUSIONS: Satisfactory objective and subjective clinical
      outcomes were disclosed in about half of the patients with mild-to-moderate LSS
      in a 12-year follow-up. The number of comorbid diseases had an unfavourable
      effect on subjective evaluation of clinical outcome. The lowest transverse
      diameter of spinal canal proved to be the only independent predictor of
      deterioration of clinical status in LSS patients.

PMID- 24943642
TI  - Comparison of neck movement smoothness between patients with mechanical neck
      disorder and healthy volunteers using the spectral entropy method.
AB  - PURPOSE: Mechanical neck disorder is one of the most common health issues. No
      related observations have applied spectral entropy to explore the smoothness of
      cervical movement. Therefore, the objectives were to ascertain whether the
      spectral entropy of time-series linear acceleration could extend to estimate the
      smoothness of cervical movement and compare the characteristics of the smoothness
      of cervical movement in patients with mechanical neck pain (MND) with healthy
      volunteers. METHODS: The smoothness of cervical movement during cervical
      circumduction from 36 subjects (MND: n = 18, asymptomatic: n = 18) was quantified
      by the spectral entropy of time-series linear acceleration and other speed
      dependent parameters, respectively. RESULTS: Patients with MND showed
      significantly longer movement time, higher value in the spectral entropy and
      wider band response in frequency spectrum than healthy volunteers (P = 0.01).
      CONCLUSIONS: The spectral entropy would be suitable to discriminate the
      smoothness of cervical movement between patients with MND with healthy volunteers
      and demonstrated patients with MND had significantly less smooth cervical
      movement.

PMID- 24943640
TI  - Volumetric change in interbody bone graft after posterior lumbar interbody fusion
      (PLIF): a prospective study.
AB  - PURPOSE: The purpose of this study is to quantify the change in the volume of the
      interbody bone graft after the PLIF and monitor the change over time for
      subsequent analysis. METHODS: The 114 cases were selected as the subjects of this
      study. The observation period was for 5 years following the surgery. The volume
      of the bone graft in the interbody space was calculated by summing up the cross
      sectional area of the bone graft on each axial image multiplied by the height (2
      mm) (the volume of the two cages was excluded). The volume ratio (%) = (bone
      graft volume)/(total volume of the interbody space - cage volume) was used for
      the purpose of evaluation. RESULTS: The volumetric change of the bone graft was
      51 % (3 months), 53 % (6 months), 54 % (1 year), 55 % (2 years), 59 % (3 years),
      62 % (4 years), and 72 % (5 years), indicating a continued increase up to the 5
      year mark. In particular, a significant increase was observed from the second
      year as compared with the previous years' result. Additionally, the volumetric
      increase from the second year to the fifth year was significantly higher than
      that before the second year. CONCLUSIONS: The post-PLIF volumes of interbody bone
      grafts exhibited increases particularly from the second to fifth years after the
      procedure. Even the elderly and those with poor bone qualities can expect to have
      volumetric increases over time. Sufficient interbody space should be secured for
      accommodating bone grafts by intraoperative reduction, wherever possible.

PMID- 24943643
TI  - Association of adenosine receptor gene polymorphisms and in vivo adenosine A1
      receptor binding in the human brain.
AB  - Adenosine A1 receptors (A1ARs) and the interacting adenosine A2A receptors are
      implicated in neurological and psychiatric disorders. Variants within the
      corresponding genes ADORA1 and ADORA2A were shown associated with
      pathophysiologic alterations, particularly increased anxiety. It is unknown so
      far, if these variants might modulate the A1AR distribution and availability in
      different brain regions. In this pilot study, the influence of ADORA1 and ADORA2A
      variants on in vivo A1AR binding was assessed with the A1AR-selective positron
      emission tomography (PET) radioligand [(18)F]CPFPX in brains of healthy humans.
      Twenty-eight normal control subjects underwent PET procedures to calculate the
      binding potential BPND of [(18)F]CPFPX in cerebral regions and to assess ADORA1
      and ADORA2A single nucleotide polymorphism (SNP) effects on regional BPND data.
      Our results revealed SNPs of both genes associated with [(18)F]CPFPX binding to
      the A1AR. The strongest effects that withstood even Bonferroni correction of
      multiple SNP testing were found in non-smoking subjects (N=22) for ADORA2A SNPs
      rs2236624 and rs5751876 (corr. Pall<0.05). SNP alleles previously identified at
      risk for increased anxiety like the rs5751876 T-allele corresponded to
      consistently higher A1AR availability in all brain regions. Our data indicate for
      the first time that variation of A1AR availability was associated with ADORA
      SNPs. The finding of increased A1AR availability in regions of the fear network,
      particularly in ADORA2A risk allele carriers, strongly warrants evaluation and
      replication in further studies including individuals with increased anxiety. 

PMID- 24943645
TI  - Cytologic features of parathyroid fine-needle aspiration on ThinPrep
      preparations.
AB  - BACKGROUND: Previous studies have provided cytologic criteria that aid in the
      recognition of parathyroid tissue on aspirate smears, including high cellularity,
      the presence of naked nuclei, loose 2-dimensional clusters, and papillary
      architecture. However, to the authors knowledge, the cytomorphologic features of
      parathyroid fine-needle aspiration (FNA) on liquid-based preparations have not
      been previously described. METHODS: The authors retrospectively reviewed all
      parathyroid FNAs that had aspirate smears and a ThinPrep preparation performed
      over 10 years at 1 institution. The FNA smears and ThinPrep preparations from
      each case were deidentified and independently reviewed for cellularity, naked
      nuclei, architecture, and colloid-like material. RESULTS: Forty patients were
      included in the current study. When individual cases were compared, the ThinPrep
      preparation was more likely to have lower cellularity, lack papillary
      architecture, lack naked nuclei, and have areas with a microfollicular pattern
      compared with the FNA smear. CONCLUSIONS: The cytologic features of parathyroid
      tissue vary depending on preparation. Many of the common features of parathyroid
      aspirates are lost on ThinPrep preparations, and an increased percentage of
      parathyroid FNA specimens have a microfollicular pattern on ThinPrep. This may
      lead to difficulty in recognizing parathyroid origin on FNA.

PMID- 24943644
TI  - Effects of genetic deletion of endogenous opioid system components on the
      reinstatement of cocaine-seeking behavior in mice.
AB  - The repeated cycles of cessation of consumption and relapse remain the major
      clinical concern in treating drug addiction. The endogenous opioid system is a
      crucial component of the reward circuit that participates in the adaptive changes
      leading to relapse in the addictive processes. We have used genetically modified
      mice to evaluate the involvement of MU-opioid receptor (MOR) and delta-opioid
      receptor (DOR) and their main endogenous ligands, the enkephalins derived from
      proenkephalin (PENK) and prodynorphin (PDYN), in the reinstatement of cocaine
      seeking behavior. Constitutive knockout mice of MOR, DOR, PENK, and PDYN, and
      their wild-type littermates were trained to self-administer cocaine or to seek
      for palatable food, followed by a period of extinction and finally tested on a
      cue-induced reinstatement of seeking behavior. The four lines of knockout mice
      acquired operant cocaine self-administration behavior, although DOR and PENK
      knockout mice showed less motivation for cocaine than wild-type littermates.
      Moreover, cue-induced relapse was significantly decreased in MOR and DOR knockout
      mice. In contrast, PDYN knockout mice showed a slower extinction and increased
      relapse than wild-type littermates. C-Fos expression analysis revealed
      differential activation in brain areas related with memory and reward in these
      knockout mice. No differences were found in any of the four genotypes in operant
      responding to obtain palatable food, indicating that the changes revealed in
      knockout mice were not due to unspecific deficit in operant performance. Our
      results indicate that MOR, DOR, and PDYN have a differential role in cue-induced
      reinstatement of cocaine-seeking behavior. 

PMID- 24943646
TI  - Facial reanimation utilizing combined orthodromic temporalis muscle flap and end
      to-side cross-face nerve grafts.
AB  - BACKGROUND: Individuals with facial paralysis of 6 months or more without
      evidence of clinical or electromyographic improvement have been successfully
      reanimated utilizing an orthodromic temporalis transfer in conjunction with end
      to-side cross-face nerve grafts. The temporalis muscle insertion is released from
      the coronoid process of the mandible and sutured to a fascia lata graft that is
      secured distally to the commissure and paralyzed hemilip. The orthodromic
      transfer of the temporalis muscle overcomes the concave temporal deformity and
      zygomatic fullness produced by the turning down of the central third of the
      muscle (Gillies procedure) while yielding stronger muscle contraction and a more
      symmetric smile. The muscle flap is combined with cross-face sural nerve grafts
      utilizing end-to-side neurorrhaphies to import myelinated motor fibers to the
      paralyzed muscles of facial expression in the midface and perioral region. Cross
      face nerve grafting provides the potential for true spontaneous facial motion. We
      feel that the synergy created by the combination of techniques can perhaps
      produce a more symmetrical and synchronized smile than either procedure in
      isolation. METHODS: Nineteen patients underwent an orthodromic temporalis muscle
      flap in conjunction with cross-face (buccal-buccal with end-to-side neurorrhaphy)
      nerve grafts. To evaluate the symmetry of the smile, we measured the length of
      the two hemilips (normal and affected) using the CorelDRAW X3 software.
      Measurements were obtained in the pre- and postoperative period and compared for
      symmetry. RESULTS: There was significant improvement in smile symmetry in 89.5 %
      of patients. CONCLUSION: Orthodromic temporalis muscle transfer in conjunction
      with cross face nerve grafts creates a synergistic effect frequently producing an
      aesthetic, symmetric smile. LEVEL OF EVIDENCE V: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors at www.springer.com/00266 .

PMID- 24943647
TI  - Novel PCA-VIP scheme for ranking MRI protocols and identifying computer-extracted
      MRI measurements associated with central gland and peripheral zone prostate
      tumors.
AB  - PURPOSE: To identify computer-extracted features for central gland and peripheral
      zone prostate cancer localization on multiparametric magnetic resonance imaging
      (MRI). MATERIALS AND METHODS: Preoperative T2-weighted (T2w), diffusion-weighted
      imaging (DWI), and dynamic contrast-enhanced (DCE) MRI were acquired from 23 men
      with confirmed prostate cancer. Following radical prostatectomy, the cancer
      extent was delineated by a pathologist on ex vivo histology and mapped to MRI by
      nonlinear registration of histology and corresponding MRI slices. In all, 244
      computer-extracted features were extracted from MRI, and principal component
      analysis (PCA) was employed to reduce the data dimensionality so that a
      generalizable classifier could be constructed. A novel variable importance on
      projection (VIP) measure for PCA (PCA-VIP) was leveraged to identify computer
      extracted MRI features that discriminate between cancer and normal prostate, and
      these features were used to construct classifiers for cancer localization.
      RESULTS: Classifiers using features selected by PCA-VIP yielded an area under the
      curve (AUC) of 0.79 and 0.85 for peripheral zone and central gland tumors,
      respectively. For tumor localization in the central gland, T2w, DCE, and DWI MRI
      features contributed 71.6%, 18.1%, and 10.2%, respectively; for peripheral zone
      tumors T2w, DCE, and DWI MRI contributed 29.6%, 21.7%, and 48.7%, respectively.
      CONCLUSION: PCA-VIP identified relatively stable subsets of MRI features that
      performed well in localizing prostate cancer on MRI.

PMID- 24943648
TI  - President's page: Letting data do the talking.

PMID- 24943652
TI  - Long-distance aerial dispersal modelling of Culicoides biting midges: case
      studies of incursions into Australia.
AB  - BACKGROUND: Previous studies investigating long-distance, wind-borne dispersal of
      Culicoides have utilised outbreaks of clinical disease (passive surveillance) to
      assess the relationship between incursion and dispersal event. In this study,
      species of exotic Culicoides and isolates of novel bluetongue viruses, collected
      as part of an active arbovirus surveillance program, were used for the first time
      to assess dispersal into an endemic region. RESULTS: A plausible dispersal event
      was determined for five of the six cases examined. These include exotic
      Culicoides specimens for which a possible dispersal event was identified within
      the range of two days--three weeks prior to their collection and novel bluetongue
      viruses for which a dispersal event was identified between one week and two
      months prior to their detection in cattle. The source location varied, but ranged
      from Lombok, in eastern Indonesia, to Timor-Leste and southern Papua New Guinea.
      CONCLUSIONS: Where bluetongue virus is endemic, the concurrent use of an
      atmospheric dispersal model alongside existing arbovirus and Culicoides
      surveillance may help guide the strategic use of limited surveillance resources
      as well as contribute to continued model validation and refinement. Further, the
      value of active surveillance systems in evaluating models for long-distance
      dispersal is highlighted, particularly in endemic regions where knowledge of
      background virus and vector status is beneficial.

PMID- 24943653
TI  - Photophysics and ex vivo biodistribution of beta-cyclodextrin-meso-tetra(m
      hydroxyphenyl)porphyrin conjugate for biomedical applications.
AB  - Low aqueous solubility of porphyrin-based photosensitizers hampers their clinical
      use in photodynamic therapy because of complex delivery. In this study, we
      explore meso-tetra(m-hydroxyphenyl)-21,23H-porphyrin (mTHPP), a potent
      photosensitizer, covalently attached to beta-cyclodextrin (CD-mTHPP) with a focus
      on topical delivery and cellular uptake. The photophysical properties of CD-mTHPP
      were examined using steady-state fluorescence and lifetime measurements verifying
      increased aqueous solubility. Confocal and fluorescence lifetime imaging
      microscopy on human squamous carcinoma cells (A431) evidenced a cytoplasmic
      uptake of CD-mTHPP in predominantly monomeric form. CD-mTHPP was also delivered
      to human skin ex vivo and the skin penetration was assessed using two-photon
      fluorescence microscopy. The results indicated that CD-mTHPP exhibits improved
      skin distribution compared to mTHPP alone using aqueous vehicles. Thus the CD
      mTHPP conjugate demonstrates improved biodistribution ex vivo compared to mTHPP
      and is a promising multimodal system for photodynamic therapy. 

PMID- 24943654
TI  - A Systematic Review of Nutritional Supplementation in HIV-Infected Children in
      Resource-Limited Settings.
AB  - BACKGROUND: In resource-limited settings, malnutrition is the major cause of
      death in young children, but the precise benefits of nutritional supplementation
      for HIV-infected children are not well understood. METHODS: Two researchers
      reviewed studies conducted in low- or middle-income countries that involved macro
      and micronutrient supplementation in HIV-infected individuals <=18 years.
      RESULTS: Fifteen studies focused on micronutrients, including vitamin A, zinc,
      multivitamins, and multiple-micronutrient supplementation. The 8 macronutrient
      studies focused on ready-to-use foods (4 studies), spirulina, whey protein,
      general food rations, and F75 and F100 starter formulas. Vitamin A was associated
      with improved mortality rates, ranging from 28% to 63%. Multiple-micronutrient
      supplementations were not associated with improvement of measured health
      outcomes. Ready-to-use foods were associated with improvement in certain
      anthropometrics. CONCLUSION: Periodic vitamin A supplementation is associated
      with reduced mortality. Macronutrient supplementation is linked to improved
      anthropometrics. More research is needed to determine how nutritional
      supplementation benefits this particularly vulnerable population.

PMID- 24943655
TI  - System and Patient Barriers to Care among People Living with HIV/AIDS in
      Houston/Harris County, Texas: HIV Medical Care Providers' Perspectives.
AB  - In the United States, a considerable number of people diagnosed with HIV are not
      receiving HIV medical care due to some barriers. Using data from the Medical
      Monitoring Project survey of HIV medical care providers in Houston/Harris County,
      Texas, we assessed the HIV medical care providers' perspectives of the system and
      patient barriers to HIV care experienced by people living with HIV/AIDS (PLWHA).
      The study findings indicate that of the 14 HIV care barriers identified, only 1
      system barrier and 7 patient barriers were considered of significant (P <= .05)
      importance, with the proportion of HIV medical care providers' agreement to these
      barriers ranging from 73.9% (cost of health care) to 100% (lack of social support
      systems and drug abuse problems). Providers' perception of important system and
      patient barriers varied significantly (P <= .05) by profession, race/ethnicity,
      and years of experience in HIV care. To improve access to and for consistent
      engagement in HIV care, effective intervention programs are needed to address the
      barriers identified especially in the context of the new health care delivery
      system. 

PMID- 24943656
TI  - An Epidemiological Study on the Awareness and Attitude of the Youths Toward AIDS
      in a Rural Area of West Bengal in India.
AB  - INTRODUCTION: This community-based cross-sectional epidemiological study was
      performed to assess the awareness and attitude of youths toward AIDS in a rural
      area of West Bengal in India. METHODS: Study population included 190 individuals
      (15-24 years). Data were collected using a semistructured, pretested
      questionnaire and analyzed using SPSS version 17 by logistic regression model.
      RESULTS: It was revealed that older youths and particularly men compared to women
      had more comprehensive knowledge of AIDS than adolescents. Education, media
      exposure, marriage, and possessing above poverty level (APL) status, all had
      stronger positive association with youths (more in men) having comprehensive
      knowledge of AIDS. Older, never married youths, and particularly men were more
      likely than adolescents to have accepting attitudes toward people living with
      HIV/AIDS. Education, media exposure, and not having below poverty level card, all
      had stronger positive association with youths having accepting attitudes toward
      women than toward men. Surprisingly among the male APL population, this
      association was negative. CONCLUSION: Educational and socioeconomic setbacks
      should be overcome in order to impose a better and justified attitude toward
      HIV/AIDS. Improved health conditions, proper counseling, and knowledge are
      essential to break the barriers of communication and ignorance toward HIV/AIDS in
      these parts of the developing countries.

PMID- 24943657
TI  - Titer and product affect the distribution of gene expression after intraputaminal
      convection-enhanced delivery.
AB  - BACKGROUND: The efficacy and safety of intracerebral gene therapy for brain
      disorders like Parkinson's disease depends on the appropriate distribution of
      gene expression. OBJECTIVES: To assess whether the distribution of gene
      expression is affected by vector titer and protein type. METHODS: Four adult
      macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-ul
      inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line
      derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the
      right and left ventral postcommissural putamen. The inoculations were conducted
      using convection-enhanced delivery and intraoperative MRI (IMRI). RESULTS: IMRI
      confirmed targeting and infusion cloud irradiation from the catheter tip into the
      surrounding area. A postmortem analysis 6 weeks after surgery revealed GFP and
      GDNF expression ipsilateral to the injection site that had a titer-dependent
      distribution. GFP and GDNF expression was also observed in fibers in the
      substantia nigra (SN) pars reticulata (pr), demonstrating anterograde transport.
      Few GFP-positive neurons were present in the SN pars compacta (pc), possibly by
      direct retrograde transport of the vector. GDNF was present in many neurons of
      the SNpc and SNpr. CONCLUSIONS: After controlling for target and infusate volume,
      the intracerebral distribution of the gene product was affected by the vector
      titer and product biology.

PMID- 24943658
TI  - Evidence of a kinetic isotope effect in nanoaluminum and water combustion.
AB  - The normally innocuous combination of aluminum and water becomes violently
      reactive on the nanoscale. Research in the field of the combustion of
      nanoparticulate aluminum has important implications in the design of molecular
      aluminum clusters, hydrogen storage systems, as well as energetic formulations
      which could use extraterrestrial water for space propulsion. However, the
      mechanism that controls the reaction speed is poorly understood. While current
      models for micron-sized aluminum water combustion reactions place heavy emphasis
      on diffusional limitations, as reaction scales become commensurate with diffusion
      lengths (approaching the nanoscale) reaction rates have long been suspected to
      depend on chemical kinetics, but have never been definitely measured. The
      combustion analysis of nanoparticulate aluminum with H2O or D2O is presented.
      Different reaction rates resulting from the kinetic isotope effect are observed.
      The current study presents the first-ever observed kinetic isotope effect in a
      metal combustion reaction and verifies that chemical reaction kinetics play a
      major role in determining the global burning rate.

PMID- 24943659
TI  - Defining health by addressing individual, social, and environmental determinants:
      new opportunities for health care and public health.
AB  - The Millennium Development Goals (MDGs) mobilized global commitments to promote
      health, socioeconomic, and sustainable development. Trends indicate that the
      health MDGs may not be achieved by 2015, in part because of insufficient
      coordination across related health, socioeconomic, and environmental initiatives.
      Explicitly acknowledging the need for such collaboration, the Meikirch Model of
      Health posits that: Health is a state of wellbeing emergent from conducive
      interactions between individuals' potentials, life's demands, and social and
      environmental determinants. Health results throughout the life course when
      individuals' potentials--and social and environmental determinants--suffice to
      respond satisfactorily to the demands of life. Life's demands can be
      physiological, psychosocial, or environmental, and vary across contexts, but in
      every case unsatisfactory responses lead to disease. This conceptualization of
      the integrative nature of health could contribute to ongoing efforts to
      strengthen cooperation across actors and sectors to improve individual and
      population health--leading up to 2015 and beyond.

PMID- 24943660
TI  - Choosing health.
AB  - The Melkirch Model is an important effort to establish a common framework for
      sustainable programs to improve health. We briefly discuss the choice to focus
      health and the assumption that individual and population wellbeing are always
      compatible. Despite the inevitable difficulties in such an ambitious endeavor,
      the Model is part of a critical conversation. 

PMID- 24943661
TI  - Emergent properties define the subjective nature of health and dis-ease.
AB  - Health and dis-ease by their etymological origins refer to an evaluative, not
      objective, state. Health is an adaptive state, constantly reestablishing itself
      through interactions between the many biological, social, emotional, and
      cognitive factors in a person's life. Such adaptive processes define health as an
      emergent state. Outcomes of emergent phenomena are not precisely predictable and
      reside in a phase space that contains all possible states ranging from perfect to
      poor health states, the latter reflecting dis-ease. However, we have seen a
      migration of meaning from the subjective, dis-ease, to the objective, disease,
      referring to uniquely identifiable biomedical change. Clinical reality though
      teaches us that many experiences of dis-ease are not associated with any
      objective abnormality, an insight with important implications for clinical care
      and health policy. 

PMID- 24943662
TI  - Impatience of health professions students for health equity--can a new definition
      help?
AB  - The International Federation of Medical Students' Associations (IFMSA) is
      concerned that students are not graduating feeling energized by their social
      purpose. IFMSA raises a question about the role of the definition of health in
      limiting the comprehensiveness of the current approach to health and health care
      in medical and health professions education. IFMSA surveyed medical students
      about medical curricula. We found that a minority of surveyed students have
      experienced interdisciplinary teaching, with the lowest exposure in low- and
      middle-income countries. Medical students are clearly stating their
      dissatisfaction with the lack of holistic and comprehensive approach to health
      and health care. Our impatience for contributing to health equity is a virtue in
      seeking change in curricula and broader collaboration for health. 

PMID- 24943663
TI  - The Meikirch Model of Health fits well into the concept of 'personalized health'.
AB  - The Meikirch Model of Health is compatible with the ongoing development of
      individualized medicine. It facilitates the conceptualization and implementation
      of personalized health. 

PMID- 24943664
TI  - What do we mean when we use the word health?

PMID- 24943665
TI  - Application of the Meikirch Model to independent medical evaluations for Social
      Security eligibility determinations in Switzerland and potential for use by
      physicians in many other situations.
AB  - The Meikirch Model of Bircher and Kuruvilla provides a new and very interesting
      definition of health and disease, based on a biopsychosocial framework and the
      idea of an interaction of an individual with social and environmental
      determinants of health. It is a modern systems approach, not only for acute, but
      particularly for chronic diseases. For this reason, I have adopted this analytic
      approach for conducting independent medical evaluations in the Swiss system of
      Social Security. 

PMID- 24943666
TI  - A cautionary note for population health: disproportionate emphasis on personal
      responsibility for health and wellbeing.
AB  - By investing in healthy human life we are investing in our social capital, the
      primary treasure of a modern technologically advanced society. In rethinking the
      definition of health from a new interdisciplinary viewpoint, I argue that health
      can be measured by satisfaction with life fulfillment and by abilities that
      permit an individual to perform tasks demanded by a society. While considering
      health as a property of a dynamic system governed by social and environmental
      determinants, a balance between societal and personal responsibility for health
      and wellbeing has to be maintained to protect those who have limited
      opportunities to "use their biologically given and personally acquired
      potentials" or to entertain their rights of healthy living standards. Instead of
      separating the biologically given and personally acquired potentials, I suggest
      capitalizing on emerging information, technologies, and materials aiming to
      enhance human potentials, both physical and intellectual. 

PMID- 24943667
TI  - Designing a framework for the concept of health.
AB  - We discuss a set of ideas related to defining health--using the World Health
      Organization definition, several debates in the academic literature, and the
      Meikirch Model of Health. Given the complex and dynamic nature of health, we
      cannot aim to generate a once-and-for-all agreement on its precise meaning.
      Instead, let us work to develop a general framework to guide further explorations
      to identify and measure the complex components and determinants of that elusive
      aspiration we call health.

PMID- 24943668
TI  - Implementation of the Meikirch Model in Odisha, India.
AB  - The National Youth Service Action and Social Development Research Institute
      (NYSASDRI) has been implementing the Meikirch Model in 100 villages in the state
      of Odisha where rates of poverty, infant and maternal mortality are the highest
      in India. Although no formal evaluation yet exists, NYSASDRI staff have monitored
      20 villages closely and associate great improvements in sanitation, malaria
      prevention, immunization, and nutrition with implementation of the Meikirch
      Model. NYSASDRI engaged in implementation with villagers and elders and with
      growing support of health practitioners, government officials, people's
      representative, media, social activists, and functionaries of other non
      governmental organizations. 

PMID- 24943669
TI  - Mild Renal Artery Stenosis Can Induce Renovascular Hypertension and is Associated
      with Elevated Renal Vein Renin Secretion.
AB  - Renovascular hypertension is a syndrome which encompasses the physiological
      response of the kidney to changes in renal blood flow and renal perfusion
      pressure. Such physiological changes can occur with renal artery occlusion
      irrespective of the severity of the lesion. We have analyzed hypertensive
      patients with mild renal artery stenosis and compared them to patients with no
      stenosis. Renal vein renin sampling from catheterization of the renal vein was
      performed in all these patients. Patients with mild stenosis had higher renal
      vein renin ratio (3.01 +/- 1.5) than the patients with no stenosis (1.10 +/-
      0.29; p = 0.002). Patients with mild stenosis were also found to have higher
      diastolic blood pressure and renal artery resistive indices when compared to
      patients with no stenosis. We therefore conclude that mild stenosis can
      precipitate renin-mediated hypertension in renovascular stenosis and also
      emphasis that parameters pertinent to renal physiology need to be evaluated
      before considering treatment options in patients with renal artery stenosis and
      medical management with RAAS blockade is the preferred modality of therapy for
      patients with renin-mediated hypertension. 

PMID- 24943670
TI  - Serum tryptase: a new biomarker in patients with acute coronary syndrome?
AB  - BACKGROUND: Mast cell tryptase has recently been reported to be involved in
      atherosclerotic plaque destabilization. However, the results of these reports are
      conflicting. METHODS: The aim of this study was to characterize the role of
      tryptase as a prognostic marker of patient cardiovascular complexity in acute
      coronary syndrome (ACS). Furthermore, its association with an angiographic
      scoring system [defined by the SYNergy between percutaneous coronary intervention
      (PCI) with the TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score]
      was examined. The serum tryptase was measured at admission in 65 consecutive ACS
      patients and in 35 healthy controls. In the patients with ACS, a composite
      measure of clinical and angiographic patient cardiovascular complexity was
      indicated by two of the following: clinical adverse events at hospitalization, at
      least 2 epicardial coronary arteries involved in the atherosclerotic disease,
      more than 1 stent implanted or more than 2 coronary artery disease risk factors.
      RESULTS: The tryptase measurements were lower in patients without the composite
      measure (p < 0.0005). Linear regression showed a significant relationship between
      tryptase levels and the SYNTAX score (SX-score). Conversely, high-sensitivity
      troponin values did not correlate with either the composite outcome or the SX
      score. The predictive accuracy of serum tryptase for the composite outcome was
      set at the cut-off point of 5.22 ng/ml (sensitivity 81% and specificity 95.7%).
      CONCLUSION: In ACS patients, serum tryptase levels at admission may predict
      patient cardiovascular complexity more reliably than currently known biomarkers.
      Further studies are needed to demonstrate the long-term prognostic role of this
      biomarker in ACS.

PMID- 24943671
TI  - The burden of norovirus gastroenteritis: an important foodborne and healthcare
      related infection.
AB  - Human norovirus (NoV) is now recognized as one of the most important causative
      agents of gastroenteritis in all age groups worldwide. During the course of NoV
      infection, symptoms are usually mild and disappear within 48 h after onset. The
      incidence of NoV infection is high, with hundreds of cases per 10 000 of the
      population, although the number of infections is still underestimated.
      Epidemiological surveys conducted in Europe and North America have shown that NoV
      infections constitute a major disease burden, especially for young children and
      the elderly, in whom NoV infection leads to high rates of hospitalization and
      mortality. NoV infections are also of concern in hospitals, where viral
      infections can be persistent in immunocompromised patients. Although the cost of
      NoV infection in the hospital community has not yet been clearly established, it
      appears that NoV infections could cost hundreds of thousands of euros in terms of
      unit closure, and NoV-related sickness in patients and health workers. Besides
      their clinical burden, NoVs, as foodborne pathogens, also cause to millions of
      dollars of losses for the healthcare system and the food industry. Recent
      estimates in the USA showed that, annually, NoV illness cost $2 billion and led
      to a loss of approximately 5000 quality-adjusted life-years, making NoV one of
      the top five pathogens causing enteric illnesses. The highest cost among 14
      foodborne pathogens is also attributed to human NoV in The Netherlands. This
      accumulation of evidence underlines the enormous impact of NoV on populations. 

PMID- 24943672
TI  - Prediction of response to interferon therapy in multiple sclerosis.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding
      interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been
      associated with disease activity in multiple sclerosis (MS) patients treated with
      interferon (IFN)-beta. We analysed whether SNPs in the IRF5, IRF8 and GPC5 genes
      are associated with clinical disease activity in MS patients beginning de novo
      treatment with IFN-beta. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in
      IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in
      575 patients with relapsing-remitting MS followed prospectively after the
      initiation of their first treatment with IFN-beta. RESULTS: 62% of patients
      experienced relapses during the first 2 years of treatment, and 32% had
      disability progression during the first 5 years of treatment. Patients with a
      pretreatment annualized relapse rate >1 had an increased risk of relapse (hazard
      ratio 1.53, 95% confidence interval 1.24-1.90) and progression (hazard ratio
      1.48, 95% confidence interval 1.10-1.99) on treatment and patients with
      breakthrough relapses in the form of relapses during the first 2 years of
      treatment had an increased risk of progression during the first 5 years of
      treatment (hazard ratio 2.04, 95% confidence interval 1.47-2.85).The gene
      variants in IRF5, IRF8 and GPC5 were not associated with risk of relapse or
      disease progression. CONCLUSIONS: Pretreatment relapse rate and clinical disease
      activity during the first 2 years of treatment may be associated with disease
      progression in MS patients treated with IFN-beta. Genetic analysis of the studied
      gene variants do not provide additional information.

PMID- 24943674
TI  - [Oral pulse granuloma of the mandible- a case report].
AB  - The oral pulse granuloma represents a rare form of oral foreign body granulomas
      and results from encapsulation of particles of vegetable nutrition.
      Histologically, the oral pulse granuloma consists of multinucleated foreign body
      type giant cells, hyaline rings and chronic inflammation tissue. Intraosseous
      granulomas can be distinguished from extraosseous granulo- mas. Intraosseous
      granulomas are often asymptomatic, whereas the extraosseous type may be
      clinically apparent as an indolent swelling of the mucosa. Therapy consists of
      curettage or surgical excision. We report on the clinical, radiological and
      histopathological characteristics of an oral pulse granuloma in the mandible
      associated with an erupting tooth 46 of a seven-year-old boy, and the surgical
      management and follow-up.

PMID- 24943673
TI  - Weight loss referrals for adults in primary care (WRAP): protocol for a multi
      centre randomised controlled trial comparing the clinical and cost-effectiveness
      of primary care referral to a commercial weight loss provider for 12 weeks,
      referral for 52 weeks, and a brief self-help intervention [ISRCTN82857232].
AB  - BACKGROUND: Recent trials demonstrate the acceptability and short term efficacy
      of primary care referral to a commercial weight loss provider for weight
      management. Commissioners now need information on the optimal duration of
      intervention and the longer term outcomes and cost effectiveness of such
      treatment to give best value for money. METHODS/DESIGN: This multicentre,
      randomised controlled trial with a parallel design will recruit 1200 overweight
      adults (BMI >=28 kg/m2) through their primary care provider. They will be
      randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for
      12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up
      for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary
      research questions are whether the CP interventions achieve significantly greater
      weight loss from baseline to 12 months than BI, and whether CP52 achieves
      significantly greater weight loss from baseline to 12 months than CP12. The
      primary outcomes will be an intention to treat analysis of between treatment
      differences in body weight at 12 months. Clinical effectiveness will be also be
      assessed by measures of weight, fat mass, and blood pressure at each time point
      and biochemical risk factors at 12 months. Self-report questionnaires will
      collect data on psychosocial factors associated with adherence, weight-loss and
      weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis
      will be conducted from an NHS perspective. Qualitative methods will be used to
      examine the participant experience. DISCUSSION: The current trial compares the
      clinical and cost effectiveness of referral to a commercial provider with a brief
      intervention. This trial will specifically examine whether providing longer
      weight-loss treatment without altering content or intensity (12 months commercial
      referral vs. 12 weeks) leads to greater weight loss at one year and is sustained
      at 2 years. It will also evaluate the relative cost-effectiveness of the three
      interventions. This study has direct implications for primary care practice in
      the UK and will provide important information to inform the decisions of
      practitioners and commissioners about service provision. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN82857232. Date registered: 15/10/2012.

PMID- 24943675
TI  - Direct, catalytic monofluorination of sp3 C-H bonds: a radical-based mechanism
      with ionic selectivity.
AB  - Recently, our group unveiled a system in which an unusual interplay between
      copper(I) and Selectfluor effects mild, catalytic sp(3) C-H fluorination. Herein,
      we report a detailed reaction mechanism based on exhaustive EPR, (19)F NMR, UV
      vis, electrochemical, kinetic, synthetic, and computational studies that, to our
      surprise, was revealed to be a radical chain mechanism in which copper acts as an
      initiator. Furthermore, we offer an explanation for the notable but curious
      preference for monofluorination by ascribing an ionic character to the transition
      state. 

PMID- 24943677
TI  - Redfin perch juveniles, Perca fluviatilis L., are resistant to European viral
      haemorrhagic septicaemia virus and infectious haematopoietic necrosis virus
      delivered via immersion in experimental condition.

PMID- 24943676
TI  - The S-layer proteins of Tannerella forsythia are secreted via a type IX secretion
      system that is decoupled from protein O-glycosylation.
AB  - Conserved C-terminal domains (CTD) have been shown to act as a signal for the
      translocation of certain proteins across the outer membrane of Bacteroidetes via
      a type IX secretion system (T9SS). The genome sequence of the periodontal
      pathogen Tannerella forsythia predicts the presence of the components for a T9SS
      in conjunction with a suite of CTD proteins. T. forsythia is covered with a two
      dimensional crystalline surface (S-) layer composed of the glycosylated CTD
      proteins TfsA and TfsB. To investigate, if T9SS is functional in T. forsythia,
      T9SS-deficient mutants were generated by targeting either TF0955 (putative C
      terminal signal peptidase) or TF2327 (PorK ortholog), and the mutants were
      analyzed with respect to secretion, assembly and glycosylation of the S-layer
      proteins as well as proteolytic processing of the CTD and biofilm formation. In
      either mutant, TfsA and TfsB were incapable of translocation, as evidenced by the
      absence of the S-layer in transmission electron microscopy of ultrathin-sectioned
      bacterial cells. Despite being entrapped within the periplasm, mass spectrometry
      analysis revealed that the S-layer proteins were modified with the complete,
      mature glycan found on the secreted proteins, indicating that protein
      translocation and glycosylation are two independent processes. Further, the T9SS
      mutants showed a denser biofilm with fewer voids compared with the wild-type.
      This study demonstrates the functionality of T9SS and the requirement of CTD for
      the outer membrane passage of extracellular proteins in T. forsythia, exemplified
      by the two S-layer proteins. In addition, T9SS protein translocation is decoupled
      from O-glycan attachment in T. forsythia.

PMID- 24943678
TI  - Authors' reply.

PMID- 24943679
TI  - Mortality after total colectomy in 3084 patients with inflammatory bowel disease:
      a population-based cohort study.
AB  - BACKGROUND: A high post-operative mortality has been reported following colectomy
      in patients with inflammatory bowel disease (IBD), especially in some patient
      groups. AIMS: To investigate the 40-day mortality following colectomy in patients
      with IBD. The secondary aim was to assess whether colectomised IBD patients have
      an increased mortality compared to the general population. METHODS: This is a
      population-based register study of all patients with IBD in Sweden who underwent
      total colectomy in 2000-2010. The cohort was identified using international
      classification codes for ulcerative colitis (UC) and Crohn's disease (CD).
      Patients registered with both UC and CD before colectomy (UCCD) were analysed
      separately. Each patient was followed-up to the date of death, migration or 31st
      of December 2010, whichever came first. Kaplan-Meier survival curves, Cox
      proportional hazards models and relative mortality rates were used to describe
      mortality. RESULTS: In the cohort of 3084 patients, 2424 were diagnosed with UC,
      326 with CD and 334 with UCCD. The 40-day, 1-year and 3-year mortality was 1.3%,
      3.1% and 6.0%, respectively. The highest 40-day mortality was seen in patients
      >=59 years of age (4.4%). Colectomy at the primary hospitalisation for IBD did
      not significantly increase the risk of post-operative mortality, nor did hospital
      volume. The relative survival after 3 years was 0.99, 0.98, 0.97 and 0.90 in
      those <30, 30-43, 44-58 and >=59 years old, respectively. CONCLUSION: The 40-day
      mortality following total colectomy in IBD patients in Sweden is low, except in
      patients >=59 years old.

PMID- 24943680
TI  - Wilcoxon's signed-rank statistic: what null hypothesis and why it matters.
AB  - In statistical literature, the term 'signed-rank test' (or 'Wilcoxon signed-rank
      test') has been used to refer to two distinct tests: a test for symmetry of
      distribution and a test for the median of a symmetric distribution, sharing a
      common test statistic. To avoid potential ambiguity, we propose to refer to those
      two tests by different names, as 'test for symmetry based on signed-rank
      statistic' and 'test for median based on signed-rank statistic', respectively.
      The utility of such terminological differentiation should become evident through
      our discussion of how those tests connect and contrast with sign test and one
      sample t-test. Published 2014. This article is a U.S. Government work and is in
      the public domain in the USA. 

PMID- 24943682
TI  - Letter regarding Wu JR et al.: S-1-based therapy versus S-1 monotherapy in
      advanced gastric cancer: a meta-analysis.

PMID- 24943681
TI  - Association of p73 G4C14-to-A4T14 polymorphism with lung cancer risk.
AB  - Conflicting results were implicated in both single case-control studies and meta
      analyses of the correlation between p73 G4C14-to-A4T14 polymorphism and lung
      cancer risk. We designed this study to further assess the association by meta
      analysis. A meta-analysis was performed based on five case-control studies (5,467
      subjects) retrieved from PubMed and Embase. Odds ratios (ORs) with 95 %
      confidence intervals (CIs) were measured for the association using the models of
      random effects and fixed effects. The results showed no evidence between p73
      G4C14-to-A4T14 polymorphism and lung cancer risk in any genetic model (allele
      model: OR, 1.06, 95 % CI, 0.89-1.26; homozygote genotypes: OR, 1.18, 95 % CI,
      0.80-1.73; heterozygote genotypes: OR, 1.04, 95 % CI, 0.89-1.23; dominant model:
      OR, 1.05, 95 % CI, 0.89-1.24; recessive model: OR, 1.17, 95 % CI, 0.93-1.47).
      Subgroup analyses according to ethnicity, however, detected significant
      association in Caucasian population. Our study provides evidence that p73 G4C14
      to-A4T14 polymorphism may play a major role in susceptibility to lung cancer in
      Caucasians.

PMID- 24943683
TI  - Identification and significance of mobilized endothelial progenitor cells in
      tumor neovascularization of renal cell carcinoma.
AB  - Neovascularization is a key role of renal cell carcinoma (RCC) and the status of
      neovascularization in RCC is closely correlated with the tumor development and
      patient prognosis. Endothelial progenitor cells (EPCs) are considered as
      important building blocks for neovascularization. However, the role of mobilized
      EPCs in RCC remains unknown. In this study, the orthotopic RCC model was
      established to investigate the distribution, frequency, and significance of
      mobilized EPCs. We found that circulating endothelial progenitor cell (CEPC)
      levels and plasma angiogenic factors (vascular endothelial growth factor (VEGF)
      and stromal cell-derived factor-1 (SDF-1) were higher in peripheral blood (PB) of
      the RCC than those in the normal group and positively correlated with each other.
      EPC levels in adjacent nonmalignant kidney tissue (AT) were significantly higher
      than those in tumor tissue (TT) and normal kidney tissue (NT), which were
      positively correlated with CEPC levels. VEGF, VEGF receptor-2 (Flk), and SDF-1
      and its SDF-1 receptor (CXCR4) expression in AT was significantly higher than
      that in TT and NT. Levels of these angiogenic factors in AT were positively
      correlated with those in PB. Mean microvessel density (MVD) was higher in AT than
      in TT, and that in TT was slightly lower than that in NT. Our findings propose
      that mobilized EPCs play an important role in RCC neovascularization. EPCs in PB
      and AT can be used as a biomarker for predicting RCC progression.

PMID- 24943684
TI  - Circulating follicular helper T cells in Crohn's disease (CD) and CD-associated
      colorectal cancer.
AB  - Follicular helper T cells (Tfh) represent a distinct subset of CD4+ T cells
      specialized in providing help to B lymphocytes. Studies have indicated that Tfh
      in circulating blood can act as a prognostic marker for diseases. In the current
      study, we investigated the percentages of circulating Tfh (CTfh) in Crohn's
      disease (CD) and CD-associated colorectal cancer (CRC). CTfh and it subtypes were
      determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 using flow cytometry in
      32 healthy controls and 78 CD patients, which included 16 CD-associated CRC. Data
      showed that proportion of CTfh in CD4+ T cells was significantly increased in CD
      patients (9.8 %) than in controls (5.1 %) (p < 0.01). Further analysis revealed
      that the upregulation of CTfh was contributed by CTfh-Th1 subtype and CTfh-Th17
      subtype. Investigating the behavior of the patients demonstrated that prevalence
      of CTfh was significantly elevated in penetrating CD (20.9 %) than inflammatory
      CD (8.2 %) or stricturing CD (7.5 %). In addition, we analyzed CTfh in CD
      associated CRC, and identified that patients with CRC had 1.59-fold higher
      percentage of CTfh than patients without CRC (p < 0.01). Furthermore, the
      distribution of CTfh subsets was significantly altered in patients with the
      cancer. This study suggests the involvement of CTfh in CD and CD-associated CRC,
      in which the effect of CTfh is partially different between these two diseases.

PMID- 24943685
TI  - Diagnostic value of microRNAs in discriminating malignant thyroid nodules from
      benign ones on fine-needle aspiration samples.
AB  - Many studies have suggested that microRNAs (miRNAs) might serve as novel
      diagnostic indicators of thyroid cancer (TC). However, inconsistent results have
      also been reported. This meta-analysis was conducted to assess the diagnostic
      value of miRNAs in discriminating malignant thyroid nodules from benign ones on
      fine-needle aspiration samples. A systematic literature search for relevant
      literature published up to April 5, 2014 was conducted in PubMed, Embase, Chinese
      National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM)
      databases. Data from different studies were pooled to estimate the summary
      sensitivity (SEN), specificity (SPE), positive likelihood ratios (PLR), negative
      likelihood ratios (NLR), diagnostic odds ratio (DOR), using the random-effect
      model. Summary receiver operator characteristic curves (SROCs) were plotted and
      areas under the SROC curve (AUC) were calculated to evaluate the overall test
      performance. Between-study heterogeneity was tested using the Q tests and the I
      (2) statistics. Potential sources of heterogeneity were analyzed through subgroup
      analyses and meta-regression. Deeks' funnel plot asymmetry test was performed to
      evaluate publication bias. All analyses were performed using STATA 12.0 software.
      Eighteen studies from 7 articles, including 543 patients with malignant thyroid
      nodules (n = 266) and benign ones (n = 277), were included in this meta-analysis.
      The pooled SEN was 0.77 (95 % CI: 0.70-0.83), SPN was 0.75 (95 % CI: 0.68-0.81),
      PLR was 3.1 (95 % CI: 2.4-4.0), NLR was 0.30 (95 % CI: 0.23-0.39), DOR was 10 (95
      % CI: 7-16), and AUC was 0.83 (95 %CI: 0.79-0.86). Subgroup analyses indicated
      that multiple miRNAs assays showed a higher diagnostic accuracy than single miRNA
      assays. In conclusion, this meta-analysis suggests that miRNAs analysis can
      significantly improve diagnostic accuracy for differentiating malignant thyroid
      nodules from benign indeterminate ones on fine-needle aspiration (FNA) samples.
      With further confirmation, multiple miRNAs assays may play a critical role as a
      complement to fine-needle aspiration biopsy (FNAB).

PMID- 24943686
TI  - Prognosis value of mitotic kinase Aurora-A for primary duodenal adenocarcinoma.
AB  - Others and we have demonstrated that hypoxia-inducible factor 1alpha (HIF-1alpha)
      and transcriptionally upregulated Aurora-A are required for disease progression
      in several tumors. We investigated the clinicopathological value of HIF-1alpha
      and Aurora-A in primary duodenal adenocarcinoma (PDA). Using
      immunohistochemistry, we evaluated Aurora-A and HIF-1alpha expression
      semiquantitatively in 140 PDA cases. There were 76 cases from one institute that
      formed the training set; 64 cases from another two institutes were used as the
      testing set to validate the prognostic value of Aurora-A and HIF-1alpha
      expression. Aurora-A expression was high or sufficient in the tumor zone, whereas
      expression was low in the adjacent normal epithelia. High Aurora-A expression,
      identified using the training set receiver operator characteristic (ROC) analysis
      generated cutoff score, predicted poorer overall survival both in the testing set
      (18.0 vs. 45.1 %, P = 0.001) and training set (23.1 vs. 53.9 %, P = 0.011).
      Multivariate Cox regression confirmed that Aurora-A was an independent prognostic
      factor. Contrary to previous studies, we did not detect any correlation between
      Aurora-A and HIF-1alpha. Survival analysis showed that HIF-1alpha level was not
      correlated with patient outcome (P = 0.466). Activation of Aurora-A, an
      independent negative prognostic biomarker, might be used to identify particular
      PDA patients for more selective therapy.

PMID- 24943688
TI  - Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulin
      like growth factor binding protein-3 (IGFBP-3) in patients with breast cancer.
AB  - Insulin-like growth factor-1 (IGF-1) and its primary binding protein-3 (IGFBP-3)
      play an important role in cellular proliferation, differentiation and apoptosis
      in many tumors, including breast cancer (BC). The objective of this study was to
      determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in
      BC patients. A total of 96 patients with a pathologically confirmed diagnosis of
      BC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined
      by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) methods.
      Age- and sex-matched 30 healthy controls were included in the analysis. The
      median age of diagnosis was 48 years (range: 29-80). Thirty-seven (39 %)
      consisted of metastatic disease. No significant difference in baseline serum was
      found in both IGF-1 and IGFBP-3 levels between BC patients and healthy controls
      (p = 0.92 and p = 0.26, respectively). None of the prognostic parameters analyzed
      was correlated significantly with the serum assay concentrations. Likewise, no
      correlations were also found between these serum concentrations and response to
      chemotherapy. No significant correlation was found between serum IGF-1 and IGFBP
      3 levels in BC patients (r s = 0.048, p = 0.66).The patients with elevated serum
      IGF-1 levels had favorable in survival than those with lower levels (p = 0.05).
      However, serum IGFBP-3 concentrations were found no prognostic role for outcome
      (p = 0.35). In conclusion, elevated serum IGF-1 level is afavorable prognostic
      factor for overall survival in BC patients.

PMID- 24943689
TI  - Serum levels of sclerostin and dickkopf-1: effects of age, gender and fracture
      status.
AB  - BACKGROUND: Fragility fractures, especially hip fractures, are a very common
      complication of osteoporosis in elderly subjects. Sclerostin (SOST) and dickkopf
      1 (DKK-1) are inhibitors of the canonical wnt signalling pathway and thus could
      be involved in the pathogenesis of age-related bone fragility. OBJECTIVE: To
      investigate SOST and DKK-1 in a large group of geriatric patients with hip
      fractures and to relate the wnt inhibitors to age and gender. METHODS: This was a
      cross-sectional study carried out in a department of acute geriatric care in a
      district hospital in Upper Austria and a hospital in Vienna, Austria. A total of
      256 geriatric patients (172 women and 84 men) and 67 young control subjects were
      selected after exclusion. Medical history was obtained, a comprehensive geriatric
      assessment was performed and serum levels of SOST, DKK-1 and bone formation
      markers were analysed. RESULTS: DKK-1 levels increased with age and in the
      presence of hip fractures. In contrast, SOST levels were lower in patients with
      hip fractures. When compared to women, men had higher SOST levels but lower DKK-1
      levels. CONCLUSION: Serum levels of the inhibitors of the canonical wnt
      signalling pathway reflect different biological events and are useful for the
      study of bone fragility in geriatric patients.

PMID- 24943687
TI  - A pilot study evaluating genetic alterations that drive tobacco- and betel quid
      associated oral cancer in Northeast India.
AB  - The susceptibility of an individual to oral cancer is mediated by genetic factors
      and carcinogen-exposure behaviors such as betel quid chewing, tobacco use, and
      alcohol consumption. This pilot study was aimed to identify the genetic
      alteration in 100 bp upstream and downstream flanking regions in addition to the
      exonic regions of 169 cancer-associated genes by using Next Generation sequencing
      with aim to elucidate the molecular pathogenesis of tobacco- and betel quid
      associated oral cancer of Northeast India. To understand the role of chemical
      compounds present in tobacco and betel quid associated with the progression of
      oral cancer, single nucleotide polymorphisms (SNPs) and insertion and deletion
      (Indels) found in this study were analyzed for their association with chemical
      compounds found in tobacco and betel quid using Comparative Toxogenomic Database.
      Genes (AR, BRCA1, IL8, and TP53) with novel SNP were found to be associated with
      arecoline which is the major component of areca nut. Genes (BARD1, BRCA2, CCND2,
      IGF1R, MSH6, and RASSF1) with novel deletion and genes (APC, BRMS1, CDK2AP1,
      CDKN2B, GAS1, IGF1R, and RB1) with novel insertion were found to be associated
      with aflatoxin B1 which is produced by fermented areca nut. Genes (ADH6, APC, AR,
      BARD1, BRMS1, CDKN1A, E2F1, FGFR4, FLNC, HRAS, IGF1R, IL12B, IL8, NBL1, STAT5B,
      and TP53) with novel SNP were found to be associated with aflatoxin B1. Genes
      (ATM, BRCA1, CDKN1A, EGFR, IL8, and TP53) with novel SNP were found to be
      associated with tobacco specific nitrosamines.

PMID- 24943690
TI  - Incidental findings in medical imaging and genetic testing: opportunities and
      challenges.

PMID- 24943691
TI  - Genomic medicine and incidental findings: balancing actionability and patient
      autonomy.

PMID- 24943692
TI  - Biobank participants' preferences for disclosure of genetic research results:
      perspectives from the OurGenes, OurHealth, OurCommunity project.
AB  - OBJECTIVE: To assess biobank participants' preferences for disclosure of genetic
      research results. PATIENTS AND METHODS: We conducted a cross-sectional survey of
      participants in the OurGenes, OurHealth, OurCommunity biobank. Respondents were
      surveyed about preferences for disclosure, importance of disclosure,
      communication of results with practitioners, and sharing of results after
      respondents' death. Multivariate regression analysis was used to assess
      independent sociodemographic and clinical predictors of disclosure preferences.
      Data collection occurred from June 6, 2011, to June 25, 2012. RESULTS: Among 1154
      biobank participants, 555 (48%) responded. Most thought that research result
      disclosure was important (90%). Preference for disclosure varied, depending on
      availability of disease treatment (90% vs 64%, P<.001), high vs low disease risk
      (79% vs 66%, P<.001), and serious vs mild disease (83% vs 68%, P<.001). More than
      half of respondents (57%) preferred disclosure even when there is uncertainty
      about the results' meaning, and 87% preferred disclosure if the disease is highly
      heritable. Older age was positively associated with interest in disclosure,
      whereas female sex, nonwhite race, diabetes mellitus, and depression and/or
      anxiety were negatively associated with disclosure. More than half of respondents
      (52%) would want their results returned to their nearest biological relative
      after death. CONCLUSIONS: OurGenes biobank participants report strong preferences
      for disclosure of research results, and most would designate a relative to
      receive results after death. Participant preferences for serious vs mild disease,
      high vs low disease risk, and availability of disease treatment differed
      significantly. Future research should consider family members' preferences for
      receiving research results from enrolled research participants.

PMID- 24943693
TI  - Imaging Pandora's Box: incidental findings in elderly patients evaluated for
      transcatheter aortic valve replacement.
AB  - OBJECTIVE: To determine the frequency and clinical impact of noncardiovascular
      incidental findings (IFs) detected on preoperative computed tomographic
      angiography (CTA) of the chest/abdomen/pelvis performed in elderly patients with
      severe aortic stenosis being considered for transcatheter aortic valve
      replacement (TAVR). PATIENTS AND METHODS: The CTA studies for 424 consecutive
      patients being evaluated for TAVR between January 1, 2009, through January 24,
      2012, were reviewed for noncardiovascular IFs (62.0% male; median +/- SD age, 82
      +/- 8.3 years). The electronic medical record was reviewed to assess for
      subsequent clinical management and survival. RESULTS: Potentially pathologic IFs
      (PPIFs) were present in 285 patients (67.2%). The mean +/- SD number of PPIFs per
      patient was 1.1 +/- 1.0 (range, 0-4). Factors associated with higher numbers of
      PPIFs were reduced ejection fraction (P=.02) and history of smoking (P=.06).
      Potentially pathologic incidental findings prompted clinical work-up in 39
      patients (9.2%) and delayed or canceled treatment plans for aortic stenosis in 7
      patients (1.7%). The number needed to image to diagnose a new malignancy or
      medical condition was 19. The number of PPIFs was predictive of poor overall
      survival before (hazard ratio, 1.58; 95% CI, 1.31-1.88) and after (hazard ratio,
      1.45; 95% CI, 1.19-1.76) adjustment for baseline clinical variables (P<.001 for
      both). CONCLUSION: This investigation found that PPIFs are common in elderly
      patients undergoing TAVR-CTA scans and, once discovered, commonly generate
      further clinical evaluation. Higher numbers of PPIFs may be predictive of poorer
      survival, but further study is required to guide the appropriateness of pursuing
      diagnostic evaluations for asymptomatic PPIFs in this elderly population.

PMID- 24943695
TI  - Transthoracic echocardiography is still useful in the initial evaluation of
      patients with suspected infective endocarditis: evaluation of a large cohort at a
      tertiary referral center.
AB  - OBJECTIVES: To examine the sensitivity of contemporary transthoracic
      echocardiography (TTE) for the detection of vegetation, abscess cavity, or
      prosthetic valve dehiscence (Vg) in patients with suspected infective
      endocarditis (IE) and to identify whether a relatively normal initial TTE finding
      can be effectively used as a rule out test, obviating the need for
      transesophageal echocardiography (TEE). PATIENTS AND METHODS: We evaluated
      clinical, microbiological, and echocardiographic data for all patients with
      suspected IE referred for both TTE and TEE between January 1, 2005, and December
      31, 2010. Patients were stratified into 3 groups by baseline TTE findings:
      negative TTE (native valves with less than or equal to mild regurgitation and no
      Vg), equivocal TTE (no Vg but prosthetic valve or greater than mild native
      valvular regurgitation), and positive TTE (Vg detected). RESULTS: We studied 622
      consecutive patients (68% male; mean +/- SD age, 62 +/- 17 years), including 256
      with Staphylococcus aureus bacteremia (SAB). The presence of Vg was confirmed by
      TEE in 141 patients (23%). The TTE had low sensitivity for the detection of Vg
      (58%). A total of 271 patients (44%) had an initial negative TTE. Of these, TEE
      demonstrated Vg in only 8 patients (negative predictive value [NPV] of negative
      TTE, 97%). The negative TTE group included 132 patients with SAB, only 6 of whom
      had Vg (NPV, 95%). Of 265 patients with equivocal TTE, Vg was demonstrated in 51
      (19%). CONCLUSION: In a hospital population with clinically suspected IE, TTE had
      low sensitivity for the detection of Vg; however, a negative initial TTE was a
      common finding, with a high NPV, even in the setting of SAB. A TEE may be avoided
      in many patients with suspected IE.

PMID- 24943694
TI  - Cardiorespiratory fitness and the paradoxical BMI-mortality risk association in
      male veterans.
AB  - OBJECTIVE: To assess the effect of fitness status on the paradoxical body mass
      index (BMI)-mortality risk association. PATIENTS AND METHODS: From February 1,
      1986, through December 30, 2011, we assessed fitness and BMI in 18,033 male
      veterans (mean age, 58.4 +/- 11.4 years) in 2 Veterans Affairs Medical centers.
      We established 3 fitness categories on the basis of peak metabolic equivalents
      achieved during an exercise test as well as 5 BMI categories. The primary outcome
      was all-cause mortality. RESULTS: During the follow-up period (median, 10.8
      years, comprising a total of 207,168 person-years), 5070 participants (28%) died.
      After adjusting for age, risk factors, muscle-wasting diseases, medications, and
      year of entry, mortality risk was higher for individuals with a BMI of 20.1 to
      23.9 kg/m(2) (hazard ratio [HR], 1.21; 95% CI, 1.12-1.30) and 18.5 to 20.0
      kg/m(2) (HR, 1.56; 95% CI, 1.37-1.77) than for those with a BMI of 24.0 to 27.9
      kg/m(2); mortality risk was not increased for those with a BMI of 28.0 kg/m(2) or
      greater. When stratified by fitness, the trend was similar for low-fit and
      moderate-fit individuals. However, mortality risk was not increased for high-fit
      individuals across BMI categories. When fitness status was considered within each
      BMI category, mortality risk increased progressively with decreased fitness and
      was more pronounced for moderate-fit (HR, 2.52; 95% CI, 2.06-3.08) and low-fit
      (HR, 2.48; 95% CI, 2.0-3.06) individuals with a BMI of 18.5-20.0 kg/m(2).
      Mortality risk was not significantly increased for high-fit individuals (HR,
      1.17; 95% CI, 0.78-1.78; P=.45). CONCLUSION: A high mortality risk associated
      with low BMI levels was observed only in moderate-fit and low-fit individuals,
      and not in high-fit individuals. Thus, fitness greatly affects the paradoxical
      BMI-mortality risk association. Furthermore, our findings indicate that lower BMI
      levels do not increase the risk for premature death as long as they are
      associated with high fitness. Thus, the paradoxically higher mortality risk
      observed with lower body weight as represented by lower BMI is likely the result
      of unhealthy reduction in body weight and, perhaps most importantly, considerable
      loss of lean body mass.

PMID- 24943696
TI  - Psychiatric adverse effects of pediatric corticosteroid use.
AB  - Corticosteroids, highly effective drugs for myriad disease states, have
      considerable neuropsychiatric adverse effects that can manifest in cognitive
      disorders, behavioral changes, and frank psychiatric disease. Recent reviews have
      summarized these effects in adults, but a comprehensive review on corticosteroid
      effects in children has not been published since 2005. Here, we systematically
      review articles published since then that, we find, naturally divide into 3 main
      areas: (1) chronic effects of acute prenatal and neonatal exposure associated
      with prematurity and congenital conditions; (2) immediate behavioral effects of
      acute exposure via oncological protocols; and (3) acute behavioral effects of
      sporadic use in children and adolescents with other conditions. PsycInfo,
      MEDLINE, Embase, and Scopus were queried to identify articles reporting
      psychiatric adverse effects of corticosteroids in pediatric patients. Search
      terms included corticosteroids, adrenal cortex hormones, steroid psychosis,
      substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone,
      prednisone, adverse effects, mood disorders, mental disorders, psychosis,
      psychotic, psychoses, side effect, chemically induced, emotions, affective
      symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent,
      pediatric, paediatric, neonatal, children, teen, and teenager. Following
      guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis,
      we have found it difficult to draw specific conclusions that are more than
      general impressions owing to the quality of the available studies. We find a
      mixed picture with neonates exposed to dexamethasone, with some articles
      reporting eventual deficits in neuropsychiatric functioning and others reporting
      no effect. In pediatric patients with acute lymphoblastic leukemia,
      corticosteroid use appears to correlate with negative psychiatric and behavioral
      effects. In children treated with corticosteroids for noncancer conditions,
      adverse effects have been observed both during treatment and after cessation,
      although the data from article to article are not consistent enough to establish
      dose relationships. By and large, inhaled corticosteroids are considered safe and
      free of severe neuropsychiatric effects. Although both antipsychotic medications
      and benzodiazepines have been used to treat corticosteroid-induced mania and
      psychosis, no unified management strategy has emerged. Large-scale standardized
      investigations are needed to clarify the psychiatric effect of corticosteroids on
      children in all these conditions. Meanwhile, there is general agreement that
      patients as well as caregivers should be warned of the potential for behavioral
      adverse effects when patients receive these drugs. 

PMID- 24943697
TI  - Concise review for physicians and other clinicians: postpartum depression.
AB  - Postpartum depression (PPD) is a common, potentially disabling, and, in some
      cases, life-threatening condition. Fortunately, PPD is also readily detectable in
      routine practice and is amenable to treatment by a wide variety of modalities
      that are effective for treating nonpuerperal major depression. Postpartum
      depression screening can improve case identification (an Edinburgh Postnatal
      Depression Scale score of >= 13 indicates a high risk of PPD) and, when
      associated with a diagnostic and follow-up program, leads to improved clinical
      outcomes. Symptom severity, patient preference, past response to treatment,
      availability of local mental health care resources, and patient decisions about
      breast-feeding will drive management decisions. In general, cognitive-behavioral
      therapy and interpersonal therapy are preferred psychotherapies for women with
      mild to moderate PPD, whereas antidepressants are appropriate in more severe
      cases. Many patients will require other types of assistance, such as parenting
      support, case management, or care coordination because many barriers to receiving
      adequate PPD treatment must still be overcome.

PMID- 24943698
TI  - 73-year-old man with recent-onset dysphagia.

PMID- 24943699
TI  - Breakthroughs in cell therapy for heart disease: focus on cardiosphere-derived
      cells.
AB  - The clinical reality of cell therapy for heart disease dates back to the 1990 s,
      when autologous skeletal myoblasts were first transplanted into failing hearts
      during open-chest surgery. Since then, the focus has shifted to bone marrow
      derived cells and, more recently, cells extracted from the heart itself. Although
      progress has been nonlinear and often disheartening, the field has nevertheless
      made remarkable progress. Six major breakthroughs are notable: (1) the
      establishment of safety with intracoronary delivery; (2) the finding that
      therapeutic regeneration is possible; (3) the increase in allogeneic cell
      therapy; (4) the effect of increasing mechanistic insights; (5) glimmers of
      clinical efficacy; and (6) the progression to phase 2 and 3 studies. This article
      individually reviews these landmark developments in detail and concludes that the
      field has reached a new phase of maturity where the prospect of clinical impact
      is increasingly imminent.

PMID- 24943701
TI  - Sensitivity of [18F]-fluorodeoxyglucose-positron emission tomography in patients
      with active myelopathy.

PMID- 24943700
TI  - Clinical practice guidelines: still miles to go...

PMID- 24943702
TI  - In reply--Sensitivity of [18F]-fluorodeoxyglucose-positron emission tomography in
      patients with active myelopathy.

PMID- 24943703
TI  - In reply--Clinical practice guidelines: still miles to go...

PMID- 24943704
TI  - A novel treatment for subacute thyroiditis: administration of a mixture of
      lidocaine and dexamethasone using an insulin pen.

PMID- 24943705
TI  - Giant uterine leiomyoma mimicking pregnancy.

PMID- 24943706
TI  - Stamp vignette on medical science. Daniel Alcides Carrion--Peruvian hero and
      medical martyr.

PMID- 24943709
TI  - Development of a rapid multiplex SSR genotyping method to study populations of
      the fungal plant pathogen Zymoseptoria tritici.
AB  - BACKGROUND: Zymoseptoria tritici is a hemibiotrophic ascomycete fungus causing
      leaf blotch of wheat that often decreases yield severely. Populations of the
      fungus are known to be highly diverse and poorly differentiated from each other.
      However, a genotyping tool is needed to address further questions in large
      collections of isolates, regarding regional population structure, adaptation to
      anthropogenic selective pressures, and dynamics of the recently discovered
      accessory chromosomes. This procedure is limited by costly and time-consuming
      simplex PCR genotyping. Recent development of genomic approaches and of larger
      sets of SSRs enabled the optimization of microsatellite multiplexing. FINDINGS:
      We report here a reliable protocol to amplify 24 SSRs organized in three
      multiplex panels, and covering all Z. tritici chromosomes. We also propose an
      automatic allele assignment procedure, which allows scoring alleles in a
      repeatable manner across studies and laboratories. All together, these tools
      enabled us to characterize local and worldwide populations and to calculate
      diversity indexes consistent with results reported in the literature. CONCLUSION:
      This easy-to-use, accurate, repeatable, economical, and faster technical strategy
      can provide useful genetic information for evolutionary inferences concerning Z.
      tritici populations. Moreover, it will facilitate the comparison of studies from
      different scientific groups.

PMID- 24943710
TI  - DNA microarray analysis of labial salivary glands in IgG4-related disease:
      comparison with Sjogren's syndrome.
AB  - OBJECTIVE: To compare gene expression in labial salivary glands (LSGs) from
      patients with IgG4-related disease with that in LSGs from patients with Sjogren's
      syndrome (SS). METHODS: Gene expression was analyzed by DNA microarray in LSG
      samples from 5 patients with IgG4-related disease, 5 SS patients, and 3 healthy
      controls. Genes differentially expressed in IgG4-related disease and SS were
      identified, and gene annotation enrichment analysis of these differentially
      expressed genes was performed using Gene Ontology (GO) annotation. Validation of
      the results was performed by quantitative polymerase chain reaction (PCR) using
      LSG samples from 9 patients with IgG4-related disease, 10 SS patients, and 4
      controls. RESULTS: Gene expression patterns in patients with IgG4-related
      disease, SS patients, and healthy controls were quite different from each other
      in hierarchical clustering as well as in principal components analysis. In IgG4
      related disease compared with SS, a total of 1,771 probe sets (corresponding to
      1,321 genes) were identified as up-regulated, and 1,785 probe sets (corresponding
      to 1,320 genes) were identified as down-regulated (false discovery rate of <5%).
      GO term analysis indicated that the up-regulated set of differentially expressed
      genes in IgG4-related disease encoded proteins that function in cell
      proliferation, extracellular matrix organization, and organ development. PCR
      validated significantly higher expression of lactotransferrin in patients with
      IgG4-related disease than in SS patients (P < 0.05) and significantly higher
      expression of CCL18 in patients with IgG4-related disease than in SS patients and
      controls (P < 0.05). CONCLUSION: The results clearly showed that the gene
      expression pattern in LSGs from patients with IgG4-related disease is different
      from that in LSGs from SS patients.

PMID- 24943711
TI  - Characterization of Bacillus strains and hoax agents by protein profiling using
      automated microfluidic capillary electrophoresis.
AB  - PURPOSE: In recent times, but especially since 2001, bioterrorism has been of
      increasing concern. In addition to the use of biological agents, including
      Bacillus anthracis (anthrax), there have been numerous hoax white powder
      "scares." It is imperative to rapidly and accurately identify any suspicious
      powder as hazardous or hoax. Classical methods for identification typically rely
      on time-consuming cultivation or highly specific molecular tests which are
      limited if the agent is unknown. Faster and field portable methods for analysis
      of suspicious powders are urgently required. METHODS: Potential hoax agents,
      including Bacillus species and household powders, were analyzed using automated
      microfluidic capillary electrophoresis to determine if protein profiling can
      distinguish between, and identify, samples. RESULTS: Distinctive protein profiles
      were produced for Bacillus species, with the presence and/or absence of certain
      bands, aiding identification. In particular B. anthracis Sterne strain contained
      a distinctive doublet band above 100 kDa which was not present in any other
      Bacillus species or hoax agents examined. The majority of powders produced
      distinctive banding that could enable the identification of the sample while
      simultaneously ruling out B. anthracis with a high degree of confidence.
      CONCLUSIONS: Results show automated microfluidic capillary electrophoresis can
      rapidly and reproducibly characterize Bacillus species and hoax agents based on
      protein profiles without the need for culture. Results were reproducible and
      there was enhanced resolution and rapidity compared to traditional protein
      profiling methods. Results show this technique is amenable to field use at a
      bioterrorism incident, thereby providing essential information to investigators
      regarding containment and treatment strategies.

PMID- 24943712
TI  - Incidence and survival for Merkel cell carcinoma in Queensland, Australia, 1993
      2010.
AB  - IMPORTANCE: Merkel cell carcinoma (MCC) is an uncommon but highly invasive form
      of skin cancer. The mechanisms that cause MCC are yet to be fully determined.
      OBJECTIVES: To compare the incidence and survival rates of MCC in Queensland,
      Australia, known to be a high-risk area, with MCC incidence and survival
      elsewhere in the world. We also analyzed incidence trends and differences in
      survival by key demographic and clinical characteristics. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective cohort study of population-based administrative data
      for MCC collected by the Queensland Cancer Registry and supplemented with
      detailed histopathologic data. Deidentified records were obtained of all
      Queensland residents diagnosed as having MCC during the period from 1993 to 2010.
      A subsample of histopathologic records were reviewed by a senior
      dermatopathologist to determine the potential for misclassification. A total of
      879 eligible cases of MCC were included in the study. MAIN OUTCOMES AND MEASURES:
      Incidence rates were directly age standardized to the 2000 United States Standard
      Population. Trends were examined using Joinpoint software with results expressed
      in terms of the annual percentage change. The period method was used to calculate
      5-year relative survival, and adjusted hazard ratios were obtained from
      multivariate Poisson models. RESULTS: There were 340 cases of MCC diagnosed in
      Queensland between 2006 and 2010, corresponding to an incidence rate of 1.6 per
      100,000 population. Men (2.5 per 100,000) had higher incidence than women (0.9
      per 100,000), and rates peaked at 20.7 per 100,000 for persons 80 years or older.
      The overall incidence of MCC increased by an average of 2.6% per year from 1993
      onwards. Relative survival was 41% after 5 years, with significantly better
      survival found for those younger than 70 years at diagnosis (56%-60%), those with
      tumors on the face or ears (51%), and those with stage I lesions (49%).
      CONCLUSIONS AND RELEVANCE: Incidence rates for MCC in Queensland are at least
      double those of any that have been previously published elsewhere in the world.
      It is likely that Queensland's combination of a predominantly white population,
      outdoor lifestyle, and exposure to sunlight has played a role in this unwanted
      result. Interventions are required to increase awareness of MCC among clinicians
      and the public.

PMID- 24943713
TI  - Limited evolutionary divergence of seedlings after the domestication of plant
      species.
AB  - The most vulnerable stage in the life of plants is the seedling. The transition
      from wild to agricultural land that plants experienced during and after
      domestication implied a noticeable change in the seedlings' environment. Building
      on current knowledge of seedling ecology, and on previous studies of cassava, we
      hypothesise that cultivation should have promoted epigeal germination of
      seedlings, and more exposed and photosynthetic cotyledons. To test this
      hypothesis, we phenotyped seedling morpho-functional traits in a set of
      domesticated and wild progenitor accessions of 20 Eudicot herbaceous crop
      species. Qualitative traits like epi- versus hypogeal germination, leafy versus
      storage type of cotyledons, or crypto- versus phanerocotyledonar germination,
      remained conserved during the domestication of all 20 species. Lengths of
      hypocotyls and epicotyls, of cotyledon petioles, and indices of cotyledon
      exposure to the aboveground environment changed during evolution under
      cultivation. However, those changes occurred in diverse directions, depending on
      the crop species. No common seedling phenotypic convergence in response to
      domestication was thus detected among the group of species studied here. Also,
      none of the 20 crops evolved in accordance with our initial hypothesis. Our
      results reject the idea that strong selective filters exerted unconsciously by
      artificial selection should have resulted in generalised channelling of seedling
      morphology towards more productive and more herbivore risky phenotypes. This
      result opens up unexplored opportunities for directional breeding of seedling
      traits. 

PMID- 24943714
TI  - Predictors of psychological distress in caregivers of older persons with wet age
      related macular degeneration.
AB  - OBJECTIVES: Several studies have investigated the biopsychosocial impacts of age
      related macular degeneration (AMD) in regards to the older patient, little is
      known about the impacts associated with caring for individuals with AMD. We aimed
      to determine the predictors of subjective caregiver distress and other negative
      outcomes associated with caring for someone with advanced AMD. METHODS: Cross
      sectional, self-complete survey involving 500 caregivers of persons with advanced
      AMD. Respondents were identified from the Macular Disease Foundation of Australia
      client database. Logistic regression tested the independent effects of care
      recipient and caregiver characteristics on study outcomes, including: caregiver
      psychological well-being, participation in recreational/social activities and
      retirement plans. RESULTS: Around one third of caregivers self-reported a high
      level of care recipient dependence. Over one in two caregivers reported a
      negative state of mind. Comorbid chronic illnesses in the care recipient were
      associated with the caregiver reporting psychological distress, multivariable
      adjusted odds ratio, OR, 1.45 (95% confidence intervals, CI, 1.14-1.86). If the
      care recipient was highly dependent on the caregiver, there was 99% greater
      likelihood of caregiver distress, OR 1.99 (95% CI 1.01-3.93). Comorbid chronic
      conditions in the care recipient was associated with 49% and 31% higher odds of
      the caregiver reporting disruption to other areas of their life and retirement
      plans related to the caregiving experience, respectively. CONCLUSIONS: A high
      prevalence of caregiver distress related to caring for persons with advanced AMD
      was observed. Level of dependence on the caregiver and presence of comorbid
      chronic illnesses were independent predictors of the caregiver experiencing
      psychological distress.

PMID- 24943716
TI  - Diabetes impairs the angiogenic potential of adipose-derived stem cells by
      selectively depleting cellular subpopulations.
AB  - INTRODUCTION: Pathophysiologic changes associated with diabetes impair new blood
      vessel formation and wound healing. Mesenchymal stem cells derived from adipose
      tissue (ASCs) have been used clinically to promote healing, although it remains
      unclear whether diabetes impairs their functional and therapeutic capacity.
      METHODS: In this study, we examined the impact of diabetes on the murine ASC
      niche as well as on the potential of isolated cells to promote neovascularization
      in vitro and in vivo. A novel single-cell analytical approach was used to
      interrogate ASC heterogeneity and subpopulation dynamics in this pathologic
      setting. RESULTS: Our results demonstrate that diabetes alters the ASC niche in
      situ and that diabetic ASCs are compromised in their ability to establish a
      vascular network both in vitro and in vivo. Moreover, these diabetic cells were
      ineffective in promoting soft tissue neovascularization and wound healing. Single
      cell transcriptional analysis identified a subpopulation of cells which was
      diminished in both type 1 and type 2 models of diabetes. These cells were
      characterized by the high expression of genes known to be important for new blood
      vessel growth. CONCLUSIONS: Perturbations in specific cellular subpopulations,
      visible only on a single-cell level, represent a previously unreported mechanism
      for the dysfunction of diabetic ASCs. These data suggest that the utility of
      autologous ASCs for cell-based therapies in patients with diabetes may be limited
      and that interventions to improve cell function before application are warranted.

PMID- 24943717
TI  - BAC-based cellular model for screening regulators of BDNF gene transcription.
AB  - BACKGROUND: Brain derived neurotrophic factor (BDNF) belongs to a family of
      structurally related proteins called neurotrophins that have been shown to
      regulate survival and growth of neurons in the developing central and peripheral
      nervous system and also to take part in synaptic plasticity related processes in
      adulthood. Since BDNF is associated with several nervous system disorders it
      would be beneficial to have cellular reporter system for studying its expression
      regulation. METHODS: Using modified bacterial artificial chromosome (BAC), we
      generated several transgenic cell lines expressing humanised Renilla luciferase
      (hRluc)-EGFP fusion reporter gene under the control of rat BDNF gene regulatory
      sequences (rBDNF-hRluc-EGFP) in HeLa background. To see if the hRluc-EGFP
      reporter was regulated in response to known regulators of BDNF expression we
      treated cell lines with substances known to regulate BDNF and also overexpressed
      transcription factors known to regulate BDNF gene in established cell lines.
      RESULTS: rBDNF-hRluc-EGFP cell lines had high transgene copy numbers when assayed
      with qPCR and FISH analysis showed that transgene was maintained episomally in
      all cell lines. Luciferase activity in transgenic cell lines was induced in
      response to ionomycin-mediated rise of intracellular calcium levels, treatment
      with HDAC inhibitors and by over-expression of transcription factors known to
      increase BDNF expression, indicating that transcription of the transgenic
      reporter is regulated similarly to the endogenous BDNF gene. CONCLUSIONS:
      Generated rBDNF-hRluc-EGFP BAC cell lines respond to known modulators of BDNF
      expression and could be used for screening of compounds/small molecules or
      transcription factors altering BDNF expression.

PMID- 24943718
TI  - The mechanism of coupling between electron transfer and proton translocation in
      respiratory complex I.
AB  - NADH-ubiquinone oxidoreductase (complex I) is the first and largest enzyme in the
      respiratory chain of mitochondria and many bacteria. It couples the transfer of
      two electrons between NADH and ubiquinone to the translocation of four protons
      across the membrane. Complex I is an L-shaped assembly formed by the hydrophilic
      (peripheral) arm, containing all the redox centres performing electron transfer
      and the membrane arm, containing proton-translocating machinery. Mitochondrial
      complex I consists of 44 subunits of about 1 MDa in total, whilst the prokaryotic
      enzyme is simpler and generally consists of 14 conserved "core" subunits.
      Recently we have determined the first atomic structure of the entire complex I,
      using the enzyme from Thermus thermophilus (536 kDa, 16 subunits, 9 Fe-S
      clusters, 64 TM helices). Structure suggests a unique coupling mechanism, with
      redox energy of electron transfer driving proton translocation via long-range (up
      to ~200 A) conformational changes. It resembles a steam engine, with coupling
      elements (akin to coupling rods) linking parts of this molecular machine.

PMID- 24943719
TI  - Selenium bioaccumulation in fish exposed to coal ash at the Tennessee Valley
      Authority Kingston spill site.
AB  - In December 2008, 4.1 million cubic meters of coal ash were released into the
      Emory and Clinch Rivers by the Tennessee Valley Authority Kingston Fossil Plant.
      Coal ash contains several contaminants, including the bioaccumulative metalloid
      selenium (Se). Because Se is predominantly accumulated in aquatic organisms
      through dietary rather than aqueous exposure, tissue-based toxicity thresholds
      for Se are currently being considered. The proposed threshold concentrations
      range between 4 MUg/g and 9 MUg/g Se (dry wt.) in whole body fish, with a
      proposed fillet threshold of 11.8 MUg/g. In the present study, the authors
      examined the spatial and temporal trends in Se bioaccumulation and examined the
      relationship between the Se content in fillets and in whole bodies of fish
      collected around the Kingston spill site to determine whether Se bioaccumulation
      was a significant concern at the ash spill site. Whereas Se concentrations in
      fish (whole bodies and fillets) were elevated at sampling locations affected by
      the Kingston ash spill relative to reference locations, concentrations do not
      appear to be above risk thresholds and have not been increasing over the 5-yr
      period since the spill. These findings are not only relevant to guiding the human
      health and ecological risk assessments at the Kingston ash spill site, but
      because of current national discussions on appropriate guidelines for Se in fish
      as well for the disposal of coal combustion wastes, the results are also relevant
      to the general understanding of Se bioaccumulation in contaminated water bodies.

PMID- 24943715
TI  - Sex-dependent diversity in ventral tegmental dopaminergic neurons and
      developmental programing: A molecular, cellular and behavioral analysis.
AB  - The knowledge that diverse populations of dopaminergic neurons within the ventral
      tegmental area (VTA) can be distinguished in terms of their molecular,
      electrophysiological and functional properties, as well as their differential
      projections to cortical and subcortical regions has significance for key brain
      functions, such as the regulation of motivation, working memory and sensorimotor
      control. Almost without exception, this understanding has evolved from landmark
      studies performed in the male sex. However, converging evidence from both
      clinical and pre-clinical studies illustrates that the structure and functioning
      of the VTA dopaminergic systems are intrinsically different in males and females.
      This may be driven by sex differences in the hormonal environment during
      adulthood ('activational' effects) and development (perinatal and/or pubertal
      'organizational' effects), as well as genetic factors, especially the SRY gene on
      the Y chromosome in males, which is expressed in a sub-population of adult
      midbrain dopaminergic neurons. Stress and stress hormones, especially
      glucocorticoids, are important factors which interact with the VTA dopaminergic
      systems in order to achieve behavioral adaptation and enable the individual to
      cope with environmental change. Here, also, there is male/female diversity not
      only during adulthood, but also in early life when neurobiological programing by
      stress or glucocorticoid exposure differentially impacts dopaminergic
      developmental trajectories in male and female brains. This may have enduring
      consequences for individual resilience or susceptibility to pathophysiological
      change induced by stressors in later life, with potential translational
      significance for sex bias commonly found in disorders involving dysfunction of
      the mesocorticolimbic dopaminergic systems. These findings highlight the urgent
      need for a better understanding of the sexual dimorphism in the VTA if we are to
      improve strategies for the prevention and treatment of debilitating conditions
      which differentially affect men and women in their prevalence and nature,
      including schizophrenia, attention/deficit hyperactivity disorder, autism
      spectrum disorders, anxiety, depression and addiction. 

PMID- 24943720
TI  - Mammalian target of rapamycin inhibitors are associated with lower rates of
      hepatocellular carcinoma recurrence after liver transplantation: a systematic
      review.
AB  - Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion
      with an increased risk of post-transplant hepatocellular carcinoma (HCC)
      recurrence. The mammalian target of rapamycin inhibitors (mTORi)
      (sirolimus/everolimus) might represent an alternative immunosuppressive regimen
      with antineoplastic effect. In the present systematic review, the association
      between mTORi and HCC recurrence after liver transplantation (LT) was evaluated
      and compared against that of CNIs-treated patients. In total, 3666 HCC liver
      transplant recipients from 42 studies met the inclusion criteria. Patients under
      CNIs developed HCC recurrence significantly more frequently, compared with
      patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although
      patients treated with CNIs had a higher proportion of HCC within Milan criteria
      (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi
      treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus had
      significantly lower recurrence rates of HCC, compared with those on sirolimus or
      CNIs (4.1% vs. 10.5% vs. 13.8%, respectively, P < 0.05), but everolimus-treated
      recipients had shorter follow-up period (13 vs. 30 vs. 43.2 months, respectively)
      and more frequently been transplanted for HCC within Milan criteria (84% vs.
      60.5% vs. 74%, respectively, P < 0.05). Our findings favor the use of mTORi
      instead of CNIs to control HCC recurrence after LT, but comparative studies with
      longer follow-up are needed for final conclusions. 

PMID- 24943721
TI  - Scaling metabolism from individuals to reef-fish communities at broad spatial
      scales.
AB  - Fishes contribute substantially to energy and nutrient fluxes in reef ecosystems,
      but quantifying these roles is challenging. Here, we do so by synthesising a
      large compilation of fish metabolic-rate data with a comprehensive database on
      reef-fish community abundance and biomass. Individual-level analyses support
      predictions of Metabolic Theory after accounting for significant family-level
      variation, and indicate that some tropical reef fishes may already be
      experiencing thermal regimes at or near their temperature optima. Community-level
      analyses indicate that total estimated respiratory fluxes of reef-fish
      communities increase on average ~2-fold from 22 to 28  degrees C. Comparisons of
      estimated fluxes among trophic groups highlight striking differences in resource
      use by communities in different regions, perhaps partly reflecting distinct
      evolutionary histories, and support the hypothesis that piscivores receive
      substantial energy subsidies from outside reefs. Our study demonstrates one
      approach to synthesising individual- and community-level data to establish broad
      scale trends in contributions of biota to ecosystem dynamics. 

PMID- 24943722
TI  - Randomized trial of artesunate-amodiaquine, atovaquone-proguanil, and artesunate
      atovaquone-proguanil for the treatment of uncomplicated falciparum malaria in
      children.
AB  - BACKGROUND: Artemisinin-based combination therapies (ACTs) are recommended for
      the treatment of acute uncomplicated falciparum malaria in many malaria-endemic
      countries. Despite the emergence of artemisinin resistance, few alternative non
      ACTs, including atovaquone-proguanil, are currently available. METHODS:
      Plasmodium falciparum-infected Cameroonian children <=5 years old (n = 338) were
      randomly assigned to artesunate-amodiaquine, atovaquone-proguanil, or artesunate
      atovaquone-proguanil treatment groups and followed for 28 days, according to the
      standard World Health Organization protocol. In vitro response to atovaquone and
      cytochrome b sequence of clinical isolates were determined. RESULTS: Eight late
      failures and 16 failures (8 late and 8 early failures) were observed after
      artesunate-amodiaquine and atovaquone-proguanil therapies, respectively. Most
      late failures were due to reinfections. Artesunate-atovaquone-proguanil was not
      associated with any failure. After correction by genotyping, per-protocol
      analysis showed no difference in the efficacy of 3 drugs. However, the proportion
      of atovaquone-proguanil-treated patients with positive smears on day 3 was much
      higher (36.0%; P < .05) than that of the artesunate-amodiaquine (2.9%) and
      artesunate-atovaquone-proguanil (1.0%) groups. In vitro response and cytochrome b
      sequence did not indicate atovaquone resistance. CONCLUSIONS: Atovaquone
      proguanil was characterized by a slow blood schizontocidal action and resulted in
      early treatment failure in a few patients. Artesunate-atovaquone-proguanil was a
      highly effective alternative treatment. CLINICAL TRIALS REGISTRATION:
      UMIN000003813.

PMID- 24943724
TI  - Interplay between the temporal dynamics of the vaginal microbiota and human
      papillomavirus detection.
AB  - BACKGROUND: We sought to describe the temporal relationship between vaginal
      microbiota and human papillomavirus (HPV) detection. METHODS: Thirty-two
      reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks
      (937 samples). Vaginal bacterial communities were characterized by pyrosequencing
      of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs).
      Each swab was tested for 37 HPV types. The effects of CSTs on the rate of
      transition between HPV-negative and HPV-positive states were assessed using
      continuous-time Markov models. RESULTS: Participants had an average of 29
      samples, with HPV point prevalence between 58%-77%. CST was associated with
      changes in HPV status (P<.001). Lactobacillus gasseri-dominated CSTs had the
      fastest HPV remission rate, and a low Lactobacillus community with high
      proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to
      L. crispatus-dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95%
      confidence interval [CI], 1.11-17.7; aTRR, 0.33, 95% CI, .12-1.19, respectively).
      The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI,
      .52-6.74). CONCLUSIONS: Vaginal microbiota dominated by L. gasseri was associated
      with increased clearance of detectable HPV. Frequent longitudinal sampling is
      necessary for evaluation of the association between HPV detection and dynamic
      microbiota.

PMID- 24943723
TI  - Higher risk of incident hepatitis C virus coinfection among men who have sex with
      men, in whom the HIV genetic bottleneck at transmission was wide.
AB  - BACKGROUND: High-risk sexual behaviors have been suggested as drivers of the
      recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among
      human immunodeficiency virus (HIV)-infected men who have sex with men (MSM).
      METHODS: We assessed the association between the genetic bottleneck of HIV at
      transmission and the prevalence and incidence of HCV coinfection in HIV-infected
      MSM from the Swiss HIV Cohort Study (SHCS). As a proxy for the width of the
      transmission bottleneck, we used the fraction of ambiguous nucleotides detected
      by genotypic resistance tests sampled during early HIV infection. We defined a
      broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously
      established threshold (0.5%). RESULTS: From the SHCS, we identified 671 MSM with
      available results of HCV serologic tests and with an HIV genotypic resistance
      test performed during early HIV infection. Of those, 161 (24.0%) exhibited a
      broad HIV transmission bottleneck, 38 (5.7%) had at least 1 positive HCV test
      result, and 26 (3.9%) had an incident HCV infection. Individuals with broad HIV
      transmission bottlenecks exhibited a 2-fold higher odds of having ever
      experienced an HCV coinfection (odds ratio, 2.2 [95% confidence interval {CI},
      1.1-4.3]) and a 3-fold higher hazard of having an incident HCV infection (hazard
      ratio, 3.0 [95% CI, 1.4-6.6]) than individuals with narrow HIV transmission
      bottlenecks. CONCLUSIONS: Our results indicate that the currently occurring
      sexual spread of HCV is focused on MSM who are prone to exhibit broad HIV
      transmission bottlenecks. This is consistent with an important role of high-risk
      behavior and mucosal barrier impairment in the transmission of HCV among MSM.

PMID- 24943725
TI  - Deep-sequencing analysis of the gene encoding the hepatitis C virus nonstructural
      3-4A protease confirms a low prevalence of telaprevir-resistant variants at
      baseline and the end of the REALIZE study.
AB  - BACKGROUND: Population sequencing (PS) has shown that telaprevir-resistant
      variants are not typically detectable at baseline (prevalence, <=5% of patients),
      and most variants present at the time of treatment failure are no longer
      detectable at the end of the study. METHODS: To gain insight into the evolution
      of telaprevir-resistant variants, their baseline prevalence and persistence after
      treatment was investigated using a more sensitive, deep-sequencing (DS) technique
      in a large number of treatment-experienced patients from the REALIZE study who
      were infected with hepatitis C virus genotype 1. RESULTS: Before treatment
      initiation, telaprevir-resistant variants (T54A, T54S, or R155K in 1%-2% of the
      viral population) were detected by DS in a fraction (2%) of patients for whom PS
      failed to detect resistance; these variants were not necessarily detected at the
      time of treatment failure. Of 49 patients in whom telaprevir-resistant variants
      were detected by PS at the time of treatment failure but not at the end of the
      study, DS revealed the presence of variants (V36A/L/M, T54S, or R155K in 1%-36%
      of the viral population) in 16 patients (33%) at the end of the study.
      CONCLUSIONS: Similar to PS findings, DS analysis revealed that the frequency of
      telaprevir-resistant variants before treatment was also low, and variants
      detected at the time of treatment failure were no longer detectable in the
      majority of patients during follow-up.

PMID- 24943726
TI  - Central memory CD4+ T cells are responsible for the recombinant Bacillus Calmette
      Guerin DeltaureC::hly vaccine's superior protection against tuberculosis.
AB  - Bacillus Calmette-Guerin (BCG) has been used for vaccination against tuberculosis
      for nearly a century. Here, we analyze immunity induced by a live tuberculosis
      vaccine candidate, recombinant BCG DeltaureC::hly vaccine (rBCG), with proven
      preclinical and clinical safety and immunogenicity. We pursue in-depth analysis
      of the endogenous mycobacteria-specific CD4(+) T-cell population, comparing the
      more efficacious rBCG with canonical BCG to determine which T-cell memory
      responses are prerequisites for superior protection against tuberculosis. rBCG
      induced higher numbers and proportions of antigen-specific memory CD4(+) T cells
      than BCG, with a CXCR5(+)CCR7(+) phenotype and low expression of the effector
      transcription factors T-bet and Bcl-6. We found that the superior protection of
      rBCG, compared with BCG, correlated with higher proportions and numbers of these
      central memory T cells and of T follicular helper cells associated with specific
      antibody responses. Adoptive transfer of mycobacteria-specific central memory T
      cells validated their critical role in protection against pulmonary tuberculosis.

PMID- 24943727
TI  - Understanding the presence of false-positive antibodies in acute hepatitis.
AB  - Although false-positive antibodies (FPAs) have been well described in chronic
      hepatitis C virus (HCV), this has not been evaluated in acute viral hepatitis.
      Patients with acute viral hepatitis underwent antibody testing for other causes
      of liver disease and sexually transmitted diseases. Those with antibody
      positivity underwent confirmatory testing and monitoring. Patients with FPAs were
      compared with patients with acute hepatitis C infection without FPAs. In total 7
      of 24 patients (29%) had FPAs. FPAs during acute viral hepatitis are associated
      with higher IgM levels and higher ESR in acute HCV. This has both mechanistic and
      clinical implications and should be evaluated further. 

PMID- 24943728
TI  - Positional OSA part 1: Towards a clinical classification system for position
      dependent obstructive sleep apnoea.
AB  - BACKGROUND: In 1984, Cartwright suggested that physicians should differentiate
      between patients with either positional obstructive sleep apnoea (POSA) or non
      positional OSA. Treatment of POSA has advanced dramatically recently with the
      introduction of a new generation of positional therapy (PT), a small device
      attached to either the neck or chest which corrects the patient from adopting the
      supine position through a vibrating stimulus. Encouraging data have been
      published suggesting that this simple therapy successfully prevents patients with
      POSA from adopting the supine position without negatively influencing sleep
      efficiency, as well as allowing for good adherence. Unfortunately, evaluating the
      efficacy of PT and comparing results are hindered by the fact that there are no
      universally used POSA criteria. In 1984, Cartwright introduced the arbitrary cut
      off point of a difference of 50% or more in apnoea index between supine and non
      supine positions. INTRODUCTION: The aim of this project was to introduce a new
      classification system, which ideally should identify suitable candidates for PT:
      patients that will benefit from a clinically significant improvement of their OSA
      with PT. The shared use of this classification can facilitate collection of data
      across multiple centres and comparison of results across studies. We report on
      the development and process that resulted in the Amsterdam Positional OSA
      Classification (APOC). METHOD: A panel of three field experts were instructed to
      independently assign the diagnosis POSA to 100 randomly selected patients they
      considered likely to benefit from a clinically significant improvement of their
      OSA with PT. In a group setting, the completed lists were compared. Discrepancies
      were discussed until consensus was met. This resulted in the consensus standard
      used to calibrate the new classification. Using the nominal group technique, the
      APOC was developed. RESULTS: The APOC criteria evolve around the percentage of
      total sleep time spent in either the worst sleeping position (WSP) or the best
      sleeping position (BSP) and the apnoea-hypopnoea index (AHI) in BSP. On applying
      APOC, one discriminates between the true positional patient, the non-positional
      patient and the multifactorial patient, whose OSA severity is influenced in part
      by sleep position. APOC has an increased sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) compared to previously
      applied POSA criteria in identifying patients that will benefit from positional
      therapy.

PMID- 24943730
TI  - Epigenetic variation reflects dynamic habitat conditions in a rare floodplain
      herb.
AB  - Variation of DNA methylation is thought to play an important role for rapid
      adjustments of plant populations to dynamic environmental conditions, thus
      compensating for the relatively slow response time of genetic adaptations.
      However, genetic and epigenetic variation of wild plant populations has not yet
      been directly compared in fast changing environments. Here, we surveyed
      populations of Viola elatior from two adjacent habitat types along a successional
      gradient characterized by strong differences in light availability. Using
      amplified fragment length polymorphisms (AFLP) and methylation-sensitive
      amplification polymorphisms (MSAP) analyses, we found relatively low levels of
      genetic (H'gen  = 0.19) and epigenetic (H'epi  = 0.23) diversity and high genetic
      (phiST  = 0.72) and epigenetic (phiST  = 0.51) population differentiation.
      Diversity and differentiation were significantly correlated, suggesting that
      epigenetic variation partly depends on the same driving forces as genetic
      variation. Correlation-based genome scans detected comparable levels of genetic
      (17.0%) and epigenetic (14.2%) outlier markers associated with site specific
      light availability. However, as revealed by separate differentiation-based genome
      scans for AFLP, only few genetic markers seemed to be actually under positive
      selection (0-4.5%). Moreover, principal coordinates analyses and Mantel tests
      showed that overall epigenetic variation was more closely related to habitat
      conditions, indicating that environmentally induced methylation changes may lead
      to convergence of populations experiencing similar habitat conditions and thus
      may play a major role for the transient and/or heritable adjustment to changing
      environments. Additionally, using a new MSAP-scoring approach, we found that
      mainly the unmethylated (phiST  = 0.60) and CG-methylated states (phiST  = 0.46)
      of epiloci contributed to population differentiation and putative habitat-related
      adaptation, whereas CHG-hemimethylated states (phiST  = 0.21) only played a
      marginal role. 

PMID- 24943729
TI  - Nursing perceptions of high-flow nasal cannulae treatment for very preterm
      infants.
AB  - AIM: This study aims to assess nursing perceptions of high-flow nasal cannulae
      (HFNC) in comparison with nasal continuous positive airway pressure (NCPAP) as
      post-extubation respiratory support for very preterm infants. METHODS: A
      standardised questionnaire form was distributed in person to nursing staff in The
      Royal Women's Hospital neonatal unit, where HFNC had been recently introduced in
      the context of a clinical trial. Nursing staff were eligible to participate if
      they routinely cared for infants receiving respiratory support. RESULTS: The
      survey was completed by 99/144 eligible nurses. The majority of the 99 nurses
      surveyed felt that HFNC was less likely than NCPAP to prevent re-intubation of
      infants 24-26 weeks' gestation but equally likely to prevent re-intubation of
      infants 28-30 weeks' gestation. Nurses preferred NCPAP for post-extubation
      support of 24- and 26-week infants, and HFNC for 28- and 30-week infants, despite
      being less experienced with HFNC. Perceptions of HFNC compared with NCPAP
      included increased ease-of-use, improved infant comfort and reduced nasal trauma.
      CONCLUSIONS: Neonatal nurses preferred NCPAP for post-extubation support of
      infants <28 weeks' gestation and HFNC for infants of 28 or 30 weeks' gestation.
      Nurses accurately predicted varying efficacy of HFNC across different gestational
      ages, consistent with the findings of a contemporaneous randomised trial. In the
      context of clinical non-inferiority, as shown in the randomised trial, nursing
      preference for HFNC over NCPAP in preterm infants >=28 weeks' gestation supports
      the use of HFNC as post-extubation support in this population.

PMID- 24943732
TI  - Dietary habits and selenium, glutathione peroxidase and total antioxidant status
      in the serum of patients with relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Dietary habits and adequate dietary intake of antioxidants in the
      diet may be one of the most important environmental factors for the prevention of
      Multiple Sclerosis (MS). OBJECTIVES: The aim of this study was to estimate
      selenium (Se) concentration, glutathione peroxidase (GSH-Px) activity and total
      antioxidant status (TAS) in the serum of patients with MS and the influence of
      dietary habits on the status. METHODS: 101 patients with relapsing-remitting MS
      (aged 18-58 years), as well as control group of 63 healthy people (aged 19-65
      years) were studied. Food-frequency questionnaires were implemented to collect
      the dietary data. Se concentration in the serum samples was determined by atomic
      absorption spectrometry. GSH-Px activity and TAS in examined serum was measured
      using the ready-made sets of tests by Randox Laboratories Ltd., UK. RESULTS:
      Serum Se concentration and GSH-Px activity in the serum of patients with MS
      (55.2+/-16.2 MUg/L, 6676.1+/-2386.4 U/L; respectively) were significantly
      decreased (p<0.01, p<0.05; respectively) compared with control group (79.2+/-20.6
      MUg/L, 8029.9+/-2650.1 U/L; respectively). A significant correlation (r=0.39,
      p<0.01) was observed between Se concentration and GSH-Px activity in the serum of
      examined patients. TAS value in the serum of patients with MS (1.03+/-0.37
      mmol/L) was also significantly lower (p<0.01) than in healthy volunteers (1.48+/
      0.41 mmol/L). Frequent consumption of poultry, bakery products, pulses and fish
      seemed to increase serum Se concentration in the group of patients; whereas
      frequent consumption of butter, wholegrain bread, sweet beverages and sugar was
      found to accompany with lower values of Se in the serum. We have observed
      significant decrease TAS (p<0.05, p<0.01; respectively) in the serum of smokers
      and those patients who received immunomodulatory drugs (0.95+/-0.39 mmol/L,
      0.92+/-0.34 mmol/L; respectively) compared with no-smoking patients and not
      taking immunomodulators (1.14+/-0.33 mmol/L, 1.31+/-0.31 mmol/L; respectively).
      CONCLUSIONS: Serum Se concentration, GSH-Px activity and TAS value were
      significantly lower in patients with relapsing-remitting MS compared with healthy
      volunteers. Dietary habits have a significant influence on Se status. Smoking
      cigarettes and intake of immunomodulatory drugs therapy have a negative impact on
      TAS of examined patients.

PMID- 24943731
TI  - Selective immunotargeting of diabetogenic CD4 T cells by genetically redirected T
      cells.
AB  - The key role played by islet-reactive CD8 and CD4 T cells in type 1 diabetes
      calls for new immunotherapies that target pathogenic T cells in a selective
      manner. We previously demonstrated that genetically linking the signalling
      portion of CD3-zeta onto the C-terminus of beta2 -microglobulin and an
      autoantigenic peptide to its N-terminus converts MHC-I complexes into functional
      T-cell receptor-specific receptors. CD8 T cells expressing such receptors
      specifically killed diabetogenic CD8 T cells, blocked T-cell-induced diabetes in
      immunodeficient NOD.SCID mice and suppressed disease in wild-type NOD mice. Here
      we describe the immunotargeting of CD4 T cells by chimeric MHC-II receptors. To
      this end we chose the diabetogenic NOD CD4 T-cell clone BDC2.5, which recognizes
      the I-A(g7) -bound 1040-31 mimotope. We assembled several constructs encoding I
      A(g7) alpha- and beta-chains, the latter carrying mim or hen egg lysozyme peptide
      as control, each supplemented with CD3-zeta intracellular portion, either with or
      without its transmembrane domain. Following mRNA co-transfection of reporter B3Z
      T cells and mouse CD8 and CD4 T cells, these constructs triggered robust
      activation upon I-A(g7) cross-linking. A BDC2.5 T-cell hybridoma activated B3Z
      transfectants expressing the mimotope, but not the control peptide, in both
      configurations. Potent two-way activation was also evident with transgenic BDC2.5
      CD4 T cells, but peptide-specific activation required the CD3-zeta transmembrane
      domain. Chimeric MHC-II/CD3-zeta complexes therefore allow the selective
      immunotargeting of islet-reactive CD4 T cells, which take part in the
      pathogenesis of type 1 diabetes. 

PMID- 24943733
TI  - Anti-arthritic activity of N'-[(2,4-dihydroxyphenyl)methylidene]-2-(3,4-dimethyl
      5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-1(4H)-yl)acetohydrazide.
AB  - Benzothiazine and pyrazole derivatives possess anti-inflammatory properties.
      Previously, synergism of both heterocyclic moieties into a single nucleus has
      shown to produce biologically active N'-arylmethylidene-2-(3,4-dimethyl-5,5
      dioxidopyrazolo(4,3-c)(1,2)benzothiazin-2(4H)yl)acetohydrazides) compound.
      Present study investigates the anti-arthritic effect and possible mechanism of
      2,4-dihydroxyphenyl derivative (DHP) in Freund's complete adjuvant-induced
      arthritic rat model. Ankle joint histopathology was performed with Hematoxylin &
      Eosin staining, while serum C-reactive protein (CRP) levels were measured by
      agglutination method. mRNA expression levels and protein levels of
      proinflammatory markers were measured by real time reverse transcription
      polymerase chain reaction and Enzyme linked immunosorbent assay (ELISA),
      respectively. in vitro Concanavalin A (ConA)-stimulated splenocyte proliferation
      was also measured by ELISA reader. DHP treatment reduced the macroscopic
      arthritic score, CRP levels, synovial inflammation, bone erosion and pannus
      formation. Levels of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2),
      Prostaglandin-E2 (PGE2), and 5-lipoxygenase (5-LOX), were significantly
      attenuated by DHP. It also significantly decreased the levels of toll-like
      receptor 2, nuclear factor-kappaB (NF-KB), and tissue necrosis factor-alpha (TNF
      alpha) and non-significantly elevated interleukin-4 (IL-4) levels. Piroxicam,
      used as reference drug, significantly reduced the levels of COX-1, COX-2, PGE2,
      NF-KB, and TNF-alpha, but did not show reduction in 5-LOX and toll-like receptor
      2 levels. However piroxicam significantly enhanced the levels of IL-4. Both DHP
      and piroxicam suppressed ConA-stimulated splenocyte proliferation. DHP normalized
      all altered hematological markers and did not show any sign of hepatotoxicity or
      nephrotoxicity as determined by alanine transaminase, aspartate aminotransferase,
      urea, and creatinine levels. Results showed that DHP possesses significant anti
      arthritic activity which may be attributed to its immunomodulatory and anti
      inflammatory effects.

PMID- 24943734
TI  - Circadian rhythm of peripheral perfusion during 10-day hypoxic confinement and
      bed rest.
AB  - INTRODUCTION: Future planetary habitats will be hypobaric and hypoxic to reduce
      the risk of decompression sickness during preparation for extra-vehicular
      activities. This study was part of a research programme investigating the
      combined effects of hypoxia and microgravity on physiological systems. PURPOSE:
      We tested the hypothesis that hypoxia-induced peripheral vasoconstriction
      persists at night and is aggravated by bed rest. Since sleep onset has been
      causally linked to nocturnal vasodilatation, we reasoned that hypoxia-induced
      vasoconstriction at night may explain sleep disturbances at altitude. Peripheral
      perfusion alterations as a consequence of bed rest may explain poor sleep quality
      reported during sojourns on the International Space Station. METHODS: Eleven
      males underwent three 10-day interventions in a randomised order: (1) hypoxic
      ambulatory confinement; (2) hypoxic bed rest; (3) normoxic bed rest. During each
      intervention we conducted 22-h monitoring of peripheral perfusion, as reflected
      by the skin temperature gradient. Measurements were conducted on the first (D 1)
      and last day (D 10) of each intervention. RESULTS: All interventions resulted in
      a decrease in daytime toe perfusion from D 1 to D 10. There was no difference in
      the magnitude of the daytime reduction in toe perfusion between the three
      interventions. There was a significant vasodilatation of the toes in all
      interventions by 11 pm. The fingertips remained well perfused throughout.
      CONCLUSIONS: Daytime vasoconstriction induced by hypoxia and/or bed rest is
      abolished at night, lending further support to the theory that changes in
      peripheral skin temperature may be functionally linked to sleep onset.

PMID- 24943735
TI  - Increased air velocity during exercise in the heat leads to equal reductions in
      hydration shifts and interleukin-6 with age.
AB  - PURPOSE: The effectiveness of increased air velocity in reducing hydration shifts
      and physiological strain during work in the heat was examined in young and older
      males. METHODS: Ten young (mean +/- SE, 24 +/- 1 years) and 10 older (59 +/- 1
      years) males, matched for height, mass, and body surface area, cycled 4 * 15-min
      at moderate-to-heavy heat production (400 W), with 15-min rest separations
      between exercise bouts (final recovery 30 min), while wearing work clothing in
      humid heat (35  degrees C, 60 % relative humidity) under low (~0.5 m s(-1)) and
      high (~3.0 m s(-1)) air velocity. Rectal temperature (T re) and heart rate were
      measured continuously, whereas hydration indices and interleukin (IL)-6 were
      measured at rest (PRE) and following the final recovery (POST). RESULTS: Young
      and older males experienced similar thermal and cardiovascular strain within the
      low (T re end-exercise: young = 38.28 +/- 0.11, older = 38.31 +/- 0.08  degrees
      C) and high (T re end-exercise: young = 37.94 +/- 0.08, older = 37.87 +/- 0.08 
      degrees C) air velocity conditions, with a reduced increase in both groups in
      high compared to low. Percent changes in plasma volume were similarly greater
      during the low (young = -10.9 +/- 1.2, older = -10.8 +/- 0.9 %) compared to high
      (young = -5.7 +/- 0.6, older = -6.9 +/- 0.7 %) condition for both groups. Despite
      elevated IL-6 at PRE in the older males, the IL-6 absolute change was similar
      between young (low = +4.10 +/- 0.95, high = +0.99 +/- 0.32 pg mL(-1)) and older
      (low = +3.58 +/- 0.83, high = +1.24 +/- 0.28 pg mL(-1)) males yet greater during
      the low compared to high condition. CONCLUSIONS: Increased air velocity was
      effective in reducing the increase in hydration shifts and physiological strain
      (i.e. IL-6, thermal and cardiovascular strain) equally in young and older males.

PMID- 24943737
TI  - Thinking in words: language as an embodied medium of thought.
AB  - Recently, there has been a great deal of interest in the idea that natural
      language enhances and extends our cognitive capabilities. Supporters of embodied
      cognition have been particularly interested in the way in which language may
      provide a solution to the problem of abstract concepts. Toward this end, some
      have emphasized the way in which language may act as form of cognitive
      scaffolding and others have emphasized the potential importance of language-based
      distributional information. This essay defends a version of the cognitive
      enhancement thesis that integrates and builds on both of these proposals. I argue
      that the embodied representations associated with language processing serve as a
      supplementary medium for conceptual processing. The acquisition of a natural
      language provides a means of extending our cognitive reach by giving us access to
      an internalized combinatorial symbol system that augments and supports the
      context-sensitive embodied representational systems that exist independently of
      language. 

PMID- 24943736
TI  - Endothelial cells mediate islet-specific maturation of human embryonic stem cell
      derived pancreatic progenitor cells.
AB  - It is well recognized that in vitro differentiation of embryonic stem cells (ESC)
      can be best achieved by closely recapitulating the in vivo developmental niche.
      Thus, implementation of directed differentiation strategies has yielded
      encouraging results in the area of pancreatic islet differentiation. These
      strategies have concentrated on direct addition of chemical signals, however,
      other aspect of the developmental niche are yet to be explored. During
      development, pancreatic progenitor (PP) cells grow as an epithelial sheet, which
      aggregates with endothelial cells (ECs) during the final stages of maturation.
      Several findings suggest that the interactions with EC play a role in pancreatic
      development. In this study, we recapitulated this phenomenon in an in vitro
      environment by maturing the human ESC (hESC)-derived PP cells in close contact
      with ECs. We find that co-culture with different ECs (but not fibroblast) alone
      results in pancreatic islet-specific differentiation of hESC-derived PP cells
      even in the absence of additional chemical induction. The differentiated cells
      responded to exogenous glucose levels by enhanced C-peptide synthesis. The co
      culture system aligned well with endocrine development as determined by
      comprehensive analysis of involved signaling pathways. By recapitulating cell
      cell interaction aspects of the developmental niche we achieved a differentiation
      model that aligns closely with islet organogenesis. 

PMID- 24943739
TI  - Intimate partner violence affects men as well as women.

PMID- 24943738
TI  - Activation of invariant natural killer T cells in regional lymph nodes as new
      antigen-specific immunotherapy via induction of interleukin-21 and interferon
      gamma.
AB  - Invariant natural killer T (iNKT) cells play important immunoregulatory functions
      in allergen-induced airway hyperresponsiveness and inflammation. To clarify the
      role of iNKT cells in allergic rhinitis (AR), we generated bone marrow-derived
      dendritic cells (BMDCs), which were pulsed by ovalbumin (OVA) and alpha
      galactosylceramide (OVA/alpha-GalCer-BMDCs) and administered into the oral
      submucosa of OVA-sensitized mice before nasal challenge. Nasal symptoms, level of
      OVA-specific immunoglobulin (IgE), and T helper type 2 (Th2) cytokine production
      in cervical lymph nodes (CLNs) were significantly ameliorated in wild-type (WT)
      mice treated with OVA/alpha-GalCer-BMDCs, but not in WT mice treated with OVA
      BMDCs. These anti-allergic effects were not observed in Jalpha18(-/-) recipients
      that lack iNKT cells, even after similar treatment with OVA/alpha-GalCer-BMDCs in
      an adoptive transfer study with CD4(+) T cells and B cells from OVA-sensitized WT
      mice. In WT recipients of OVA/alpha-GalCer-BMDCs, the number of interleukin (IL)
      21-producing iNKT cells increased significantly and the Th1/Th2 balance shifted
      towards the Th1 dominant state. Treatment with anti-IL-21 and anti-interferon
      (IFN)-gamma antibodies abrogated these anti-allergic effects in mice treated with
      alpha-GalCer/OVA-BMDCs. These results suggest that activation of iNKT cells in
      regional lymph nodes induces anti-allergic effects through production of IL-21 or
      IFN-gamma, and that these effects are enhanced by simultaneous stimulation with
      antigen. Thus, iNKT cells might be a useful target in development of new
      treatment strategies for AR.

PMID- 24943741
TI  - Waiting list randomized controlled trial within a case-finding design:
      methodological considerations.
AB  - RATIONALE, AIMS AND OBJECTIVES: Randomized controlled trials (RCTs) are widely
      used in health care research to provide high-quality evidence of effectiveness of
      an intervention. However, sometimes a study does not require an RCT in order to
      answer its primary objective; a case-finding design may be more appropriate. The
      aim of this paper was to introduce a new study design that nests a waiting list
      RCT within a case-finding study. METHODS: An example of the new study design is
      the DOC Study, which primarily aims to determine the diagnostic accuracy of lung
      function tests for chronic obstructive pulmonary disease. It also investigates
      the impact of lung function tests on smoking behaviour through use of a waiting
      list design. The first step of the study design is to obtain participants'
      consent. Individuals are then randomized to one of two groups; either the
      'intervention now' group or the 'intervention later' group, that is, participants
      are placed on a waiting list. All participants receive the same intervention; the
      only difference between the groups is the timing of the intervention. RESULTS AND
      CONCLUSIONS: The design addresses patient preference issues and recruitment
      issues that can arise in other trial designs. Potential limitations include
      differential attrition between study groups and potential demoralization for the
      'intervention later' group. The 'waiting list case-finding trial' design is a
      valuable method that could be applied to case-finding studies; the design enables
      the case-finding component of a study to be maintained while simultaneously
      exploring additional hypotheses through conducting a trial.

PMID- 24943740
TI  - Plasminogen activator-1 overexpression decreases experimental postthrombotic vein
      wall fibrosis by a non-vitronectin-dependent mechanism.
AB  - BACKGROUND: Factors associated with postthrombotic syndrome are known clinically,
      but the underlying cellular processes at the vein wall are not well delineated.
      Prior work suggests that vein wall damage does not correlate with thrombus
      resolution but rather with plasminogen activator-1 (PAI-1) and matrix
      metalloproteinase (MMP) activity. OBJECTIVE: We hypothesized that PAI-1 would
      confer post venous thrombosis (VT) vein wall protection via a vitronectin (Vn)
      dependent mechanism. METHODS: A stasis model of VT was used with harvest over 2
      weeks, in wild-type, Vn(-/-) , and PAI-1-overexpressing mice (PAI-1 Tg). RESULTS:
      PAI-1 Tg mice had larger VT at 6 and 14 days, compared to controls, but Vn(-/-)
      mice had no alteration of VT resolution. Gene deletion of Vn resulted in an
      increase in, rather than the expected decrease in, circulating PAI-1 activity.
      While both Vn(-/-) and PAI-1 Tg had attenuated intimal fibrosis, PAI-1 Tg had
      significantly less vein wall collagen and a compensatory increase in collagen III
      gene expression. Both Vn(-/-) and PAI-1 Tg vein wall had less monocyte
      chemotactic factor-1 and fewer macrophages (F4/80), with significantly less MMP-2
      activity and decreased TIMP-1 antigen. Ex vivo assessment of transforming growth
      factor beta-mediated fibrotic response showed that PAI-1 Tg vein walls had
      increased profibrotic gene expression (collagens I and III, MMP-2, and alpha
      smooth muscle actin) compared with controls, opposite of the in vivo response.
      CONCLUSIONS: The absence of Vn increases circulating PAI-1, which positively
      modulates vein wall fibrosis in a dose-dependent manner. Translationally, PAI-1
      elevation may decrease vein wall damage after deep vein thrombosis, perhaps by
      decreasing macrophage-mediated activities.

PMID- 24943742
TI  - Physicochemical characterization of nanoparticles and their behavior in the
      biological environment.
AB  - Whilst the physical and chemical properties of nanoparticles in the gas or
      idealized solvent phase can nowadays be characterized with sufficient accuracy,
      this is no longer the case for particles in the presence of a complex biological
      environment. Interactions between nanoparticles and biomolecules are highly
      complex on a molecular scale. The detailed characterization of nanoparticles
      under these conditions and the mechanistic knowledge of their molecular
      interactions with the biological world is, however, needed for any solid
      conclusions with regards to the relationship between the biological behavior of
      such particles and their physicochemical properties. In the present article we
      discuss some of the challenges with characterization and behavior of
      nanoparticles that are associated with their presence in chemically complex
      biological environments. Our focus is on the stability of colloids as well as on
      the formation and characteristics of protein coronae that have recently been
      shown to significantly modify the properties of pristine particles. Finally, we
      discuss the perspectives that may be expected from an improved understanding of
      nanoparticles in biological media. 

PMID- 24943743
TI  - Treatment policy rather than patient characteristics determines convection volume
      in online post-dilution hemodiafiltration.
AB  - BACKGROUND/AIMS: Sub-analyses of three large trials showed that hemodiafiltration
      (HDF) patients who achieved the highest convection volumes had the lowest
      mortality risk. The aims of this study were (1) to identify determinants of
      convection volume and (2) to assess whether differences exist between patients
      achieving high and low volumes. METHODS: HDF patients from the CONvective
      TRAnsport STudy (CONTRAST) with a complete dataset at 6 months (314 out of a
      total of 358) were included in this post hoc analysis. Determinants of convection
      volume were identified by regression analysis. RESULTS: Treatment time, blood
      flow rate, dialysis vintage, serum albumin and hematocrit were independently
      related. Neither vascular access nor dialyzer characteristics showed any relation
      with convection volume. Except for some variation in body size, patient
      characteristics did not differ across tertiles of convection volume. CONCLUSION:
      Treatment time and blood flow rate are major determinants of convection volume.
      Hence, its magnitude depends on center policy rather than individualized patient
      prescription.

PMID- 24943744
TI  - Indian Journal of Pathology and Microbiology. From the Editor's desk.

PMID- 24943745
TI  - Absence of anaplastic lymphoma kinase-1 expression in inflammatory
      myofibroblastic tumors of the central nervous system: does it signify a different
      nosologic entity from its systemic counterpart?
AB  - BACKGROUND AND AIM: Inflammatory myofibroblastic tumors (IMFTs) are uncommon
      neoplasms of the central nervous system (CNS) of intermediate grade biologic
      potential. Anaplastic lymphoma kinase (ALK-1), a diagnostic marker of anaplastic
      large cell lymphoma, is also expressed in a subset of IMFTs and appears to have
      prognostic significance. Though, few studies have evaluated expression of ALK-1
      in IMFTs of the CNS. This retrospective study was undertaken to evaluate the
      expression of ALK-1 expression in IMFT of CNS by immunohistochemistry and
      correlate with the clinical, radiological and pathologic features. MATERIALS AND
      METHODS: Five cases diagnosed as IMFT/inflammatory pseudotumour/plasma cell
      granuloma, diagnosed in CNS over 10 year period (1998-2007) were retrieved from
      the archives of Department of Neuropathology of a tertiary referral center. The
      clinical profile and imaging features were collected from the case records.
      Hematoxylin and eosin stained sections were reviewed with immunohistochemistry
      for smooth muscle actin (SMA), vimentin, desmin, ALK-1, p53, MIB-1, CD68,
      leukocyte common antigen, CD3, and CD20. RESULTS: All five cases of IMFTs
      presented as dural-based space occupying or en-plaque lesions. Histologically,
      four cases had combined plasma cell granuloma-fibrous histiocytoma morphology,
      and one had fibrous histiocytoma-like morphology. Immunohistochemically, SMA was
      strongly positive in spindle cell component of the tumors confirming diagnosis.
      ALK-1 expression could not be detected by immunohistochemistry in any of the
      cases. CONCLUSION: Further studies analyzing ALK-1 gene mutation and
      rearrangements are required to determine pathogenetic role, if any, in CNS IMFTs.

PMID- 24943746
TI  - Secretory meningioma: a diagnostic pitfall.
AB  - CONTEXT: Secretory meningioma is a rare subtype of meningiomas, displaying
      epithelial and secretory differentiation of meningothelial cells. It has unique
      radiological, morphological, and immunohistochemical features, but runs a benign
      course. Radiological picture because of the variable degrees of peritumoral edema
      can be confused with aggressive neoplasms. Morphologically, it is difficult to
      distinguish secretory meningioma from other tumors having a clear cell appearance
      and aggressive clinical behavior. MATERIALS AND METHODS: Retrospective analysis
      over a period of 16 years (1997-2012) brought out five cases diagnosed as
      secretory meningioma. The slides were restained and subject to special stains and
      immunohistochemistry and the clinical details were retrieved. RESULTS: On
      histopathology, the tumors showed a characteristic vacuolated appearance due to
      the presence of variably sized intracytoplasmic lumina. Another unique feature
      was the presence of hyaline inclusions within these intracytoplasmic lumina and
      in the intercellular spaces. These inclusions were periodic acid-Schiff positive
      diastase-resistant, yellowish-orange on Elastic Van Giesson stain and strongly
      carcinoembryonic antigen positive. CONCLUSION: Owing to its rarity and unique
      morphology secretory meningioma poses a diagnostic challenge to the pathologists.
      As this tumor follows a benign course, it is crucial to correctly diagnose this
      entity to avoid unnecessary over treatment.

PMID- 24943747
TI  - Cytopathic effects of toxogenic strains of Helicobacter pylori on different cell
      lines.
AB  - PURPOSE: Many virulence factors are involved in the pathomechanism of infection
      caused by Helicobacter pylori. Toxins such as vacuolating cytotoxin, encoded by
      the vacA gene and the immunogenic protein cagA, encoded by the cagA gene
      (cytotoxin-associated gene) are major factors conferring the property of
      virulence. The current study is aimed at isolation of H. pylori and separation of
      its toxin from antral biopsies of patients. MATERIALS AND METHODS: The following
      cell lines were used to demonstrate the cytopathic effect (CPE) of the separated
      toxin: African green monkey kidney (Vero), baby hamster kidney, human lung
      carcinoma (LLC-MK2), and human epithelial. RESULTS: H. pylori was isolated from
      27 out of 45 patients (60%) selected for the study. CPE of H. pylori toxin was
      highly significant on Vero cells than other cell lines used as it reached a high
      dilution titer of toxin (1/16) in 13 isolated strains (48.15%). No significant
      difference in CPE of toxin in different dilutions was detected among other cell
      lines used in different groups. H. pylori toxin could be detected by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis as a distinct band
      with a molecular weight ranging between 66 and 97 kDa and closely related to 87
      kDa. CONCLUSION: H. pylori vacuolating cytotoxin plays a vital role in the
      pathogenesis of gastroduodenal diseases (gastritis, gastric ulcer, duodenal
      ulcer, and gastric cancer). The Vero cell lines were found to be the most
      suitable form of tissue culture when compared with other cell lines used in our
      study for demonstrating the activity of H. pylori toxin.

PMID- 24943748
TI  - Hemangiomas versus arterio-venous malformations: role of elastic stains and mast
      cell density.
AB  - CONTEXT: Vascular anomalies present diagnostic challenges to histopathologists.
      Mulliken and Glowacki's classification categorizes vascular lesions into
      hemangiomas and vascular malformations. AIM: This study explored diagnostic clues
      in the histomorphology of hemangiomas and vascular malformations. MATERIALS AND
      METHODS: A total of 120 cases of benign vascular lesions were retrieved from 12
      years period. A total of 94 cases, where complete clinical details and
      representative paraffin sections were available, were included in this study.
      Hematoxylin and eosin (H and E) stain and Verhoeff's stain for elastic tissue
      were done on all cases and lesions were classified into hemangiomas or arterio
      venous malformations (AVM). Mast cell density in all lesions was calculated from
      toluidine blue stained sections. RESULTS: Ten cases of hemangiomas were
      reclassified as AVM on the basis of presence and absence of arteriovenous
      structures. Intra-lesional nerves were seen in significantly higher number of
      AVMs compared to hemangiomas. Medium and thick sized nerve bundles were seen in
      56% of AVMs, while they were not seen in any of the hemangiomas. Mean mast cell
      density was significantly higher in proliferating hemangiomas (53.12 +/- 27.83
      cells/mm2) compared to involuting hemangiomas (11.43 +/- 7.9 cells/mm2).
      CONCLUSIONS: Use of elastic tissue stains are useful ancillary tools to
      distinguish between AVMs and hemangiomas. The presence of arteries and arterioles
      are an integral part of AVMs. The presence of the intra-lesional nerves can be
      useful to distinguish between AVMs and hemangiomas even on H and E stained
      sections. The significantly higher mast cell density seen in proliferating
      hemangiomas compared with involuting ones, seem to suggest that mast cells play
      an important role in the natural history of these lesions.

PMID- 24943749
TI  - Efficacy of the seven feature, fifteen point histological scoring system and CD56
      in interpretation of liver biopsies in persistent neonatal cholestasis: a five
      year study.
AB  - CONTEXT: Neonatal cholestasis (NC) lasting more than 2 weeks affects one in 2500
      live births. Extrahepatic biliary atresia (EHBA) and idiopathic neonatal
      hepatitis account for about 70% of all cases of NC. Differentiating these two
      conditions is important as patient management is very different for both the
      conditions. AIMS: To assess the usefulness of the seven-feature, 15-point
      histological scoring system in the interpretation of liver biopsy in NC and
      usefulness of immunostaining with CD56 (N-CAM) in EHBA. SETTINGS AND DESIGN:
      Retrospective study of 5 years' duration at a pediatric referral institute, where
      the case load of NC is high and definitive surgery for EHBA is undertaken after
      histological confirmation. MATERIALS AND METHODS: The study is of a 5-year
      duration conducted between June 2007 and May 2012. A total of 210 cases of NC
      were clinically diagnosed during this period. All the slides were reviewed with
      reference to a seven-feature, 15-point histological scoring system assessing its
      usefulness in the interpretation of liver biopsy in NC and utility of the
      immunohistochemical marker CD56 was also assessed as an aid in the
      characterization of bile ductular proliferation in EHBA. STATISTICAL ANALYSIS:
      Statistical analysis was performed and sensitivity and specificity of the
      histological scoring system for EHBA was analyzed. RESULTS: Of the 210 liver
      biopsies reviewed using the scoring system, 122 cases were diagnosed as EHBA and
      88 cases were diagnosed as other causes of NC. The overall sensitivity of this
      scoring system was 95.5%, specificity was 93.1% and diagnostic accuracy was
      94.6%. CONCLUSIONS: The seven-feature, 15-point histological scoring system has
      good diagnostic accuracy in the interpretation of liver histology in NC as
      advanced histopathological findings even at younger age require immediate
      surgery. CD-56 is a useful marker in the assessment of bile ductular
      proliferation in EHBA.

PMID- 24943750
TI  - Inter-observer agreement in reporting HER 2 Neu protein over expression by
      immunohistochemistry.
AB  - INTRODUCTION: HER 2 Neu protein overexpression and its detection by
      immunohistochemistry (IHC) has become quiet critical because of its relevance in
      regards to Herceptin treatment. This peer review was done at a tertiary care
      center, which aimed at determining the inter-observer variation among five
      pathologists and evaluating the degree of agreement between them. AIMS: The aim
      of our study was to determine the reproducibility of HER 2 Neu system of
      reporting in breast cancer cases and determine inter-observer variability among
      five pathologists at a tertiary care center. To compare the results with similar
      studies done at other centers. SETTINGS AND DESIGN: Retrospective descriptive
      study. MATERIALS AND METHODS: Hematoxylin and Eosin (H and E) and IHC stained
      slides of 104 cases of carcinoma breast, on which HER 2 Neu status had been
      reported were reviewed. The time period for selection was from January 2010 to
      December 2011 (2 year period). Five pathologists reviewed the H and E and IHC
      slides independently and scored the results on a specially designed work sheet.
      Kappa values for inter-observer variation and Cornbach's alpha for internal
      consistency were calculated. STATISTICAL ANALYSIS USED: SPSS 20.0 (IBM). not
      known. RESULTS: Complete agreement was seen between all five pathologists in 70
      cases (70/104) = 67%. Agreement between four pathologists was seen in 78 cases
      (78/104) = 75%. Agreement between three pathologists was seen in 92 cases
      (92/104) = 88%. The global value for kappa co efficient for agreement between two
      pathologists was 0.706 and Cornbach alpha for internal consistency of reporting
      in the department was 0.987. CONCLUSION/KEY MESSAGES: Our departmental peer
      review indicated that there is good inter-observer concordance (agreement between
      two pathologists) and there is strong overall internal consistency of reporting
      for HER 2 Neu reporting by IHC. Our results are comparable to International
      reported data of similar studies.

PMID- 24943751
TI  - Expression of tumor necrosis factor-alpha and nuclear factor-kappaB/RelA and the
      pathogenesis of psoriasis.
AB  - CONTEXT: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in the
      pathogenesis of psoriasis. Nuclear factor-kappaB (NF-kappaB) is a transcription
      factor that regulates the activity of the proinflammatory genes. Psoriasis is an
      inflammatory disease and the role of TNF-alpha and NF-kappaB, should be
      considerable. AIMS: We studied the role of TNF-alpha and NF-kappaB in psoriasis.
      MATERIALS AND METHODS: A total of 61 cases of psoriatic skin biopsies were
      studies and the grade of TNF-alpha and NF-kappaB, staining was correlated with
      the histopathological indices of severity. STATISTICAL ANALYSIS USED: Pearson's
      correlation coefficient and Chi-square test. Statistical Package for Social
      Sciences version 13 was used. RESULTS: The TNF-alpha immunostain in the cytoplasm
      of the epidermal cells and basal cells showed a strong inverse correlation with
      the grade of epidermal hyperplasia (P -0.019 and P -0.009, respectively). The
      epidermal cytoplasmic positivity and lymphocyte positivity for TNF-alpha did not
      correlate with the grade of NF-kappaB immunostaining in the epidermal cell
      nuclei, basal cells or lymphocytes. The basal cell cytoplasmic positivity for TNF
      alpha correlated with the grade of NF-kappaB immunostaining in the nucleus of
      basal cells at a P - 0.005. There was a strong correlation between the epidermal
      cytoplasmic TNF-alpha immunostaining with the lymphocyte immunostaining (P 
      0.08); however, there was no correlation between the TNF-alpha expression in the
      other two locations. CONCLUSIONS: The study outlines the relationship between NF
      kappaB and TNF-alpha and their combined role in the development of the
      characteristic histopathological changes in psoriasis. We hypothesize that NF
      kappaB is involved in stimulating the release of TNF-alpha which would account
      for the characteristic histopathological changes of psoriasis. However, it is
      likely that NF-kappaB can act independently of TNF-alpha also in the pathogenesis
      of psoriasis.

PMID- 24943752
TI  - Cytokeratin expression in gastrointestinal stromal tumors: morphology, meaning,
      and mimicry.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are biologically distinctive
      neoplasms harboring KIT and PDGFRA mutations. Cytokeratin expression in GISTs is
      an under-recognized diagnostic pitfall, especially in high grade GISTs with
      limited biopsy material and from metastatic sites. MATERIALS AND METHODS: We
      evaluated the histomorphology and expression of four 'broad-spectrum' cytokeratin
      markers, AE1-AE3, CAM 5.2, MNF-116, and 34betaE12 in 64 GISTs diagnosed over a 68
      month period. Individual cytokeratins 5, 6, 7, 8, 14, 17, 18, 19, and 20 were
      investigated in the 'broad-spectrum' cytokeratin-positive GISTs. RESULTS: Of 64
      GISTs, 10 (15%) demonstrated cytokeratin immunopositivity. All 10, considered
      high risk by the National Institutes of Health consensus approach, were
      immunopositive for CAM 5.2 and MNF-116. Seven were AE1-AE3 immunopositive.
      Cytokeratins 8 and 18 were confirmed in 10 and 9 GISTs, respectively. One GIST
      demonstrated biphasic morphology with cytokeratin immunonegativity in low-grade
      spindle and immunopositivity in high-grade epithelioid foci. KIT and PDGFRA
      mutational analysis, undertaken in 5/10 cytokeratin-positive GISTs, harbored KIT
      exon 11 mutations. CONCLUSION: We hypothesize that cytokeratin expression
      exclusively in high risk GISTs is a consequence of tumor progression. Given the
      increasing number of commercially available broad-spectrum cytokeratin
      immunomarkers, including those reacting with cytokeratins 8 and 18, cytokeratin
      positive GISTs must be differentiated from carcinomas, melanomas, and a range of
      cytokeratin-positive sarcomas to ensure optimal patient management and
      prognostication.

PMID- 24943753
TI  - Diagnostic utility of melanin production by fungi: study on tissue sections and
      culture smears with Masson-Fontana stain.
AB  - BACKGROUND: Dematiaceous fungi appear brown in tissue section due to melanin in
      their cell walls. When the brown color is not seen on routine H and E and culture
      is not available, differentiation of dematiaceous fungi from other fungi is
      difficult on morphology alone. AIMS AND OBJECTIVE: To study if melanin production
      by dematiaceous fungi can help differentiate them from other types of fungi.
      MATERIALS AND METHODS: Fifty tissue sections of various fungal infections and 13
      smears from cultures of different species of fungi were stained with Masson
      Fontana stain to assess melanin production. The tissue sections included biopsies
      from 26 culture-proven fungi and 24 biopsies of filamentous fungi diagnosed on
      morphology alone with no culture confirmation. RESULTS: All culture-proven
      dematiaceous fungi and Zygomycetes showed strong positivity in sections and
      culture smears. Aspergillus sp showed variable positivity and intensity.
      Cryptococcus neoformans showed strong positivity in tissue sections and culture
      smears. Tissue sections of septate filamentous fungi (9/15), Zygomycetes (4/5),
      and fungi with both hyphal and yeast morphology (4/4) showed positivity for
      melanin. The septate filamentous fungi negative for melanin were from biopsy
      samples of fungal sinusitis including both allergic and invasive fungal sinusitis
      and colonizing fungal balls. CONCLUSION: Melanin is produced by both dematiaceous
      and non-dematiaceous fungi. Masson-Fontana stain cannot reliably differentiate
      dematiaceous fungi from other filamentous fungi like Aspergillus sp; however,
      absence of melanin in the hyphae may be used to rule out dematiaceous fungi from
      other filamentous fungi. In the differential diagnosis of yeast fungi,
      Cryptococcus sp can be differentiated from Candida sp by Masson-Fontana stain in
      tissue sections.

PMID- 24943754
TI  - Colposcopy: gynecological vision in viewing oral lesions.
AB  - CONTEXT: The diagnosis of malignant and potentially malignant epithelial lesions
      of the oral mucosa cannot be based solely on clinical findings. The histologic
      evaluation of a representative biopsy specimen thus becomes necessary. The site
      for biopsy however is always a subjective choice that sometimes raises doubts
      about its representativeness. So far, no simple and reliable method is available
      for the selection of the most appropriate area for biopsy. Colposcopy is helpful
      in the selection of these sites of epithelial dysplasia depending upon the
      vascular patterns. AIMS: This study was planned to assess the role of Colposcopic
      examination in the selection of biopsy site in patients with varying grades of
      oral epithelial dysplasia at various sites. SETTINGS AND DESIGN: One hundred and
      eighty patients between the ages of 30 and 60 years clinically diagnosed with
      leukoplakia and carcinoma buccal mucosa were included in the study. MATERIALS AND
      METHODS: For each of the subjects, a thorough clinical examination followed by
      Colposcopic assessment was carried out for the selection of biopsy site from the
      involved mucosa. The histopathological findings were then compared in the two
      cases and results analyzed. STATISTICAL ANALYSIS USED: The statistical analysis
      was performed using a paired t-test. RESULTS: In our study, sensitivity and
      specificity for the selection of biopsy site by Colposcopic examination was found
      to be higher for leukoplakia than for carcinoma buccal mucosa. CONCLUSIONS: It
      was concluded that Colposcopic examination was found to be significant in the
      selection of biopsy site for leukoplakia while clinical criterion was found to be
      more appropriate for carcinoma buccal mucosa cases.

PMID- 24943755
TI  - Establishing biological reference intervals for novel platelet parameters
      (immature platelet fraction, high immature platelet fraction, platelet
      distribution width, platelet large cell ratio, platelet-X, plateletcrit, and
      platelet distribution width) and their correlations among each other.
AB  - AIMS: This study aims to establish biological reference interval for novel
      platelet parameters. SETTINGS AND DESIGN: A total of 945 healthy individuals, age
      ranges from 18 to 64 years (881 males and 64 females) coming for voluntary blood
      donation from June to August 2012 (3 months) were enrolled after exclusion of
      rejection criteria. MATERIALS AND METHODS: The samples were assayed by running in
      complete blood count + reticulocyte mode on the Sysmex XE-2100 hematology
      analyzer and the reference interval for the population was calculated using
      Clinical and Laboratory Standards Institute guidelines. STATISTICAL ANALYSIS
      USED: Tests were performed using SPSS (Statistical Product and Service Solutions,
      developed by IBM corporation), version 13. Student t test and pearsons
      correlation analysis were also used. RESULTS: The normal range for various
      parameters was platelet count: 150-520 * 10(3)/cu mm, immature platelet fraction
      (IPF): 0.3-8.7%, platelet distribution width (PDW): 8.3-25.0 fL, mean platelet
      volume (MPV): 8.6-15.5 fL, plateletcrit (PCT): 0.15-0.62%, high immature platelet
      fraction (H-IPF): 0.1-2.7%, platelet large cell ratio (P-LCR): 11.9-66.9% and
      platelet-X (PLT-X) (ch): 11.0-22.0. Negative correlation was observed between
      platelet count (r = -0.468 to r = -0.531; P < 0.001) and PCT (r = -0.080 to r = 
      0.235; P < 0.05 to P < 0.001) with IPF, PDW, MPV, H-IPF, P-LCR, and platelet-X.
      IPF/H-IPF showed a positive correlation among them and also with PDW, MPV, P-LCR,
      platelet-X (r = +0.662 to r = +0.925; P < 0.001). CONCLUSIONS: These novel
      platelet parameters offer newer avenues in research and clinical use.
      Establishing biological reference interval for different platelet parameters
      would help determine true high and low values and help guide treatment decisions.

PMID- 24943756
TI  - Pattern of hemoglobinopathies and thalassemias in upper Assam region of North
      Eastern India: high performance liquid chromatography studies in 9000 patients.
AB  - BACKGROUND: The hereditary hemoglobin (Hb) disorders are the most commonly
      encountered single gene disorders in India. Data pertaining to the pattern of
      hemoglobinopathies and thalassemias is scarce in North East India, and hence it
      was considered worthwhile to study these disorders using a large series of
      patients referred to a clinical diagnostic laboratory. AIMS: A total of 9000
      patients referred for Hb variant analysis were studied to identify
      hemoglobinopathies and thalassemias in Upper Assam region of North East India.
      MATERIALS AND METHODS: This study was performed by high performance liquid
      chromatography (HPLC) using BIORAD variant Hb typing system. RESULTS: Out of 9000
      patients studied, abnormal Hb fractions were seen in 5320 patients. The HbE gene
      was detected in 4315 patients of which HbE trait was seen in 2294 followed by HbE
      disease in 1892. There were 114 HbE beta thalassemia patients and 15 double
      heterozygotes of HbE with HbS or HbD. Beta thalassemia trait was seen in 313
      patients and beta thalassemia homozygous in 32. HbS gene was detected in 460
      patients comprising of HbS trait in 189, HbS disease in 203, S beta thalassemia
      in 53 and double heterozygotes of SD and ES in 15. The rest comprised of HbD
      trait in 6, delta beta thalassemia in 33, hereditary persistence of fetal
      hemoglobin trait in 5 and J chain hemoglobinopathy in 8 patients. Evidence of
      alpha thalassemia though suspected, could not be confirmed. CONCLUSION: A high
      incidence of hemoglobinopathies and thalassemias and their combinations is unique
      for this part of the country.

PMID- 24943757
TI  - Molecular detection of ESBLs production and antibiotic resistance patterns in
      Gram negative bacilli isolated from urinary tract infections.
AB  - BACKGROUND: beta-lactam resistance is more prevalent in Gram negative bacterial
      isolates worldwide, particularly in developing countries. In order to provide
      data relating to antibiotic therapy and resistance control, routine monitoring of
      corresponding antibiotic resistance genes is necessary. AIMS: The aim of this
      study was the characterization of beta-lactam resistance genes and its plasmid
      profile in bacteria isolated from urinary tract infection samples. MATERIALS AND
      METHODS: In this study, 298 Gram negative bacteria isolated from 6739 urine
      specimens were identified by biochemical standard tests. Antimicrobial
      susceptibility testing was performed by the disk diffusion method. Extended
      spectrum beta-lactamase (ESBL)-producing strains were also detected by the double
      disk synergy test. The presence of blaTEM and blaSHV genes in the strains studied
      was ascertained by polymerase chain reaction. RESULTS: Of all Gram negative
      bacteria, Escherichia coli (69.1%) was the most common strain, followed by
      Klebsiella sp. (12.1%), Enterobacter sp. (8.4%), Proteus sp. (4.4%), Citrobacter
      (4%) and Pseudomonas sp. (2%). The most antibiotic resistance was shown to
      tetracycline (95.16%), nalidixic acid (89.78%) and gentamycin (73.20%)
      antibiotics. Among all the strains tested, 35 isolates (11.75%) expressed ESBL
      activity. The prevalence of TEM and SHV positivity among these isolates was
      34.29%, followed by TEM (31.43%), TEM and SHV negativity (20.0%) and SHV
      (14.29%), respectively. CONCLUSIONS: Regular monitoring of antimicrobial drug
      resistance seems necessary to improve our guidelines in the use of the empirical
      antibiotic therapy.

PMID- 24943758
TI  - Prevalence of blaTEM , blaSHV and blaCTX-M genes in clinical isolates of
      Escherichia coli and Klebsiella pneumoniae from Northeast India.
AB  - AIM: This study was carried out to determine the presence of blaTEM , blaSHV and
      blaCTX-M genes in extended-spectrum beta-lactamase (ESBL) producing Escherichia
      coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) at a tertiary care
      referral hospital in Northeast India. MATERIALS AND METHODS: A total of 270 E.
      coli and 219 K. pneumoniae isolates were recovered during the period between
      August 2009 and July 2010. Kirby-Bauer disk diffusion method was performed to
      determine the antibiotic resistance pattern. Screening and phenotypic
      confirmatory test for ESBL production were performed using standard disc
      diffusion methods. Each of the initial ESBL screening test isolate was
      investigated for the presence of blaTEM , blaSHV and blaCTX-M genes via
      polymerase chain reaction (PCR) using gene-specific primers. RESULTS: Phenotypic
      confirmatory test able to detect ESBL production in 73.58% of E. coli and 67.24%
      of K. pneumoniae. However, PCR amplification showed the presence of one or more
      ESBL genes in each of the initial ESBL screening positive isolate. Among three
      ESBL genotypes, the most prevalent genotype was found to be blaCTX-M in E. coli
      (88.67%) and blaTEM in K. pneumoniae (77.58%) ESBL producing isolates. Majority
      of ESBL producing isolates possess more than one ESBL genes. CONCLUSION: This
      study constituted a primer report on high prevalence of blaTEM and blaCTX-M genes
      in ESBL producing isolates of E. coli and K. pneumoniae and denotes the need of
      more extensive studies on these antibiotic genes to determine the magnitude of
      the problem of antibiotic resistance exiting in this locality.

PMID- 24943759
TI  - Characterization of plasmid mediated AmpC producing Escherichia coli clinical
      isolates from a tertiary care hospital in South India.
AB  - CONTEXT: Plasmid mediated AmpC (pAmpC) beta-lactamase producing Escherichia coli
      are an emerging problem worldwide as they are now exhibiting resistance to
      multiple classes of antibiotics and are a major cause of therapeutic failure.
      AIMS: The aim of this study was to characterize pAmpC beta-lactamase producing
      extraintestinal E. coli, their phylogenetic distribution, resistance pattern,
      treatment options, and impact on patient's clinical outcome. SETTINGS AND DESIGN:
      This descriptive study was carried out in a multi-specialty tertiary care
      hospital. MATERIALS AND METHODS: A total of 300 clinically significant, non
      repeat isolates were studied. AmpC disk test was used for phenotypic AmpC-beta
      lactamase detection. Molecular types of pAmpC were determined by a multiplex
      polymerase chain reaction (PCR). Phylogenetic analysis was performed by triplex
      PCR methods. Metallo-beta-lactamase (MBL) detection was done by E test.
      Antibiogram, treatment, and clinical outcome were collected in a structured
      proforma. RESULTS: Although 95 isolates (32%) were phenotypically positive for
      AmpC, PCR detected CIT type of AmpC gene in only 37 isolates. Majority of strains
      were from phylogroup A (85%) and B1 (58%) which are considered as commensal
      groups. Co-production of ESBL's was observed in 33 strains and 5 strains were
      found to be MBL producers. Most widely prescribed antibiotics were 3 rd
      generation cephalosporins (30%), carbapenems (19%) and aminoglycosides (16%).
      CONCLUSIONS: Plasmid mediated AmpC producing isolates were found to exhibit a
      high degree of drug resistance, and they mainly belonged to commensal strains
      possibly due to misuse of antibiotics. Proper antibiotic policy is required to
      limit the spread of pAmpC producers or else it will lead to a therapeutic dead
      end in the near future.

PMID- 24943760
TI  - Periodontal pathogens in atheromatous plaque.
AB  - BACKGROUND: There has been increasing attention paid in recent years to the
      possibility that oral bacterial infection, particularly periodontal disease may
      influence the initiation and or progression of systemic diseases. These studies
      confirm the observation that heart disease is the most commonly found systemic
      condition in patients with periodontal disease. Moreover, the literature has also
      highlighted substantial evidence indicating the presence of Gram-negative
      periodontal pathogens in atheromatous plaques. AIM: This study intends to
      investigate the possible association between periodontal health and coronary
      artery disease by evaluating periodontal status, association between the
      periodontal plaque and coronary atheromatous plaques for presence of micro
      organisms such as, Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis, Prevotella intermedia, and Tannerella forsythia. MATERIALS AND
      METHODS: A case-control study was designed with seven patients who had undergone
      coronary endarterectomy for cardiovascular disease and 28 controls. The
      periodontal examination for cases was performed 1 day before vascular surgery and
      the controls were clinically examined. The atheromatous plaque sample collected
      during endarterectomy and the intraoral plaque samples were subjected to
      polymerase chain reaction for identification of A. actinomycetemcomitans, P.
      gingivalis, P. intermedia and T. forsythia. RESULTS: The presence of periodontal
      bacteria DNA in coronary atheromatous plaques and sub-gingival plaque samples of
      the same patients was confirmed by this study. CONCLUSION A correlation was
      established between putative bacteria contributing to atheromatous plaques and
      species associated with periodontal disease. One particularly important study to
      be carried out is the investigation of a possible clinically meaningful reduction
      in coronary heart disease resulting from the prevention or treatment of
      periodontal disease.

PMID- 24943761
TI  - Significance of Mycobacterium tuberculosis antigen expression in cerebrospinal
      fluid monocytes in diagnosing tuberculous meningitis.
AB  - BACKGROUND: The aim of this study was to investigate the significance of positive
      expression of Mycobacterium tuberculosis, (MTB) antigen in the cerebrospinal
      fluid (CSF) monocytes in diagnosing tuberculous meningitis (TBM). MATERIALS AND
      METHODS: A total of 50 inpatients of TBM, 30 viral meningitis and 20 healthy
      controls were studied at the 1 st , 2 nd , and 4 th week during their treatment
      course. Immunohistochemical assay were used to detect early secreted antigenic
      target 6 (ESAT-6) positive cells, and positive cases were also observed. RESULTS:
      The percentage of positive cases and positive cells of ESAT-6 in CSF monocytes
      were all higher in the 1 st and 2 nd week than in the 4 th week in TBM patients
      (P < 0.01); and percentage of positive cases and positive cells of MTB antigen in
      CSF monocytes were higher in TBM patients than in viral meningitis and health
      control in the 1 st and 2 nd week (P < 0.01). The sensitivity was 90% and the
      specificity was 92% in the early stage (within 2 weeks) of TBM. CONCLUSION: The
      positive expression of ESAT-6 in CSF monocytes is helpful for the early diagnosis
      of TBM.

PMID- 24943762
TI  - Intraosseous myoepithelioma: a rare, distinct tumor entity.
AB  - Primary musculoskeletal myoepithelial tumors (METs) are distinctly rare tumors
      and are being increasingly recognized as a result of improved diagnostic criteria
      and objective confirmation with immunohistochemical markers, including epithelial
      markers. Recent studies have unraveled distinct molecular mechanisms underlying
      these tumors. Herein, we present our second diagnosed case of an intraosseous MET
      that occurred in the tibia of a 37-year-old lady. The case is discussed with
      regards to current clinicopathological perspectives on these rather uncommon
      tumors, including our personal experience. 

PMID- 24943763
TI  - Isosporiasis in a tertiary care center of North India.
AB  - BACKGROUND: Cystoisospora (Isospora) belli is a coccidian, protozoan parasite
      that resides in the gastrointestinal tract of humans. It is mainly reported from
      HIV-positive individuals. However, a few cases have been reported in other
      immunosuppressed individuals including renal transplant patients, and those with
      lymphoma and leukemia. MATERIALS AND METHODS: During a period of 5 years (2008
      2012), approximately 1700 stool samples of immunosuppressed patients were
      screened for the presence of opportunistic parasitic infections by a modified
      acid fast staining technique. RESULTS: A total of 41 C. belli were reported, out
      of which 30 were HIV-positive individuals while 11 were HIV negative. The latter
      individuals were also immunosuppressed due to prolonged use of steroids or other
      immunosuppressive drugs. Twenty-six out of 30 HIV-positive patients and all the
      HIV-negative individuals with C. belli infection had diarrhea. CONCLUSION: All
      immunosuppressed individuals should be examined for the presence of opportunistic
      coccidian parasitic infections and treated accordingly and alternatively,
      isolation of opportunistic parasites should trigger a hunt for immunocompromised
      state to reduce the morbidity and mortality in such patients.

PMID- 24943764
TI  - Multidrug-resistant Staphylococcus hominis subsp. novobiosepticus causing
      septicemia in patients with malignancy.
AB  - A new subspecies of Staphylococcus hominis described by Kloos et al. in 1998 and
      named S. hominis subsp. novobiosepticus (SHN) has been implicated in nosocomial
      outbreaks. Multidrug resistance, including resistance to novobiocin and
      oxacillin, is a particularly important feature of SHN. In our institute, we
      encountered 13 cases of S. hominis subsp. hominis in cancer patients with
      septicemia, of which seven were methicillin resistant. The isolates were
      identified by VITEK (r) 2 compact automated system, using GP REF 21342
      identification card and antimicrobial susceptibility testing card P-628. The
      biochemical reactions and antibiotic susceptibility pattern of the seven
      methicillin-resistant isolates were re-analyzed and patient details were re
      checked to finally identify them as SHN. The increasing number of cases reporting
      isolation of SHN from biological specimens point to potential virulence and
      clinical importance of this bacterium. 

PMID- 24943765
TI  - Primary yolk sac tumor of the cerebellar vermis: a case report.
AB  - Extragonadal germ cell tumors are rare and comprise 2-5% of all germ cell tumors.
      Seminoma/dysgerminoma, teratoma, yolk sac tumor (YST) and mixed germ cell tumors
      are few of the extragonadal germ cell tumors arising within the brain. Of these,
      primary pure YSTs arising in the brain are extremely rare and arise in the pineal
      (62%) and suprasellar (31%) regions. Primary YST occurring in the cerebellum is
      exceedingly rare, associated with a very poor prognosis and has been reported in
      less than 10 cases in literature. We herein report a case of primary pure yolk
      sac tumor in the cerebellar vermis in a 2-year-old child. 

PMID- 24943766
TI  - Bilateral multiple axillary apocrine hidrocystomas accompanied by apocrine
      hyperplasia: a rare presentation.
AB  - Apocrine hidrocystomas (AHC) are uncommon cystic lesions of apocrine glands and
      are most often solitary. They are usually found in the head and neck region.
      Multiple AHC have been rarely reported in the literature usually in the eyelids
      and face. On extensive search of literature, we came across only a single case
      report of multiple axillary AHC. We report a case of a 31-year-old female who
      presented with fullness and discomfort in bilateral axillae, so a clinical
      diagnosis of bilateral accessory breast was made. However on histopathological
      examination, it turned out to be bilateral multiple AHC associated with apocrine
      hyperplasia. 

PMID- 24943767
TI  - A case report of a urothelial carcinoma arising in the renal pelvis with
      exuberant chondrosarcomatous element associated with adrenal metastasis.
AB  - Sarcomatoid carcinoma is a rare malignant tumor that has both malignant
      epithelial and mesenchymal components. We describe a sarcomatoid carcinoma
      arising in the left renal pelvis of a 49-year-old man. The dominant component of
      the tumor was chondrosarcomatous, but there were also focal carcinomatous areas.
      The carcinomatous tumor cells consisted of papillary urothelial carcinoma.
      Immunohistochemical assay showed that the sarcomatous tumor cells were positive
      for vimentin and S 100 and negative for cytokeratin. The papillary urothelial
      carcinoma was positive for cytokeratin and negative for vimentin. The patient
      underwent neoadjuvant chemotherapy and after downsizing the tumor, radical
      nephrectomy was performed with excision of the cuff of bladder. 

PMID- 24943768
TI  - Malignant melanoma of breast: a unique case with diagnostic dilemmas.
AB  - Melanomas arising in the skin, mucous membranes, and eye are encountered commonly
      than melanomas involving the breast. Melanomas in the breast are usually
      metastatic. Primary melanoma of the breast is extremely rare. We report a case of
      malignant melanoma of breast (primary/metastatic) that presented as a breast lump
      in a patient with no detectable cutaneous, mucosal or ocular lesion and who is a
      known case of squamous cell carcinoma of the oral cavity and had relapsed twice.
      The unexpected challenges faced during the diagnosis prompted us to report this
      case. 

PMID- 24943769
TI  - Adenomatoid odontogenic tumor with clear cell changes.
AB  - Adenomatoid odontogenic tumor (AOT) has a limited biological profile and been an
      attention-grabbing tumor for a century for its origin. Though described earlier,
      it was widely accepted after Harbitz from Norway reported about this uncommon
      benign tumor in 1915. There has been a long debate as whether this tumor is a
      hamartoma or a neoplasm. Here, we present a case of AOT in a 20-year-old female
      with details of clinical, radiological and histological features along with clear
      cell changes, signifying AOT to be more aggressive in nature than assessed from
      earlier literature. Thus, we did an extensive search of PubMed literature on AOT
      with all its histopathological features associated until date to find the report
      of clear cell changes yet. 

PMID- 24943770
TI  - Large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal
      differentiation: a case report of a rare tumor.
AB  - Medulloblastoma is an embryonal neuroepithelial tumor of the cerebellum and is
      the most common malignant central nervous system tumor in children. Different
      histological variants and patterns have been described. The classic variant
      represents the majority of cases. This report describes a rare case of large
      cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal
      differentiation arising in the cerebellum of a 3-year-old boy who presented with
      headache and vomiting. Magnetic resonance imaging demonstrated a heterogeneously
      enhanced lesion in the fourth ventricle. Surgical resection of the tumor was
      accomplished, but a residual tumor was left behind because of the involvement of
      the brainstem. Postoperatively, the patient received chemotherapy and
      radiotherapy. Currently, 20 months after treatment, the patient has survived
      without further progression. Pathological examination revealed a high grade
      primitive neuronal tumor with foci of myogenic features, melanin containing
      epithelial elements and ganglion-like cells, which were confirmed by
      immunohistochemistry. 

PMID- 24943771
TI  - Primary primitive neuroectodermal tumor of kidney: a rare case report with
      diagnostic challenge.
AB  - Primary primitive neuroectodermal tumors (PNETs) of the kidney are quite rare and
      can be mistaken for a wide variety of other small round blue cell tumors which
      includes rhabdomyosarcoma, Wilm's tumor, carcinoid, neuroblastoma, clear cell
      sarcoma of the kidney, lymphoma etc. Renal Ewings/PNET can occur in the age group
      from 4 to 61 years. Approximately, 90% of Ewing sarcoma (ES)/PNET have a specific
      t(11;22) which results in a chimeric EWS-FLI-1 fusion protein.
      Immunohistochemical for the carboxy-terminus of FLI-1 is sensitive and highly
      specific for the diagnosis of ES/PNET. Herein, we have an interesting
      presentation in a 23-year-old male who came with neck pain and progressive
      quadriparesis and was diagnosed as a case of poorly differentiated malignant
      tumor with a differential of lymphoma versus metastatic renal cell carcinoma. The
      patient's condition deteriorated fast and he had a rapid downhill course. The
      final diagnosis of Ewings/PNET was confirmed at autopsy. 

PMID- 24943772
TI  - Intraosseous angiolipoma of the frontal bone with a unique location: a clinical
      and pathological case illustration and review of the literature.
AB  - Here, we report a case of a 16-year-old female patient was referred with scalp
      swelling and headache. Her neurological examination was normal and imaging of the
      skull revealed a well-defined lytic lesion measuring 15 mm * 6 mm to the right of
      the frontal bone. She was operated on with a prediagnosis of Langerhans cell
      histiocytosis. A wide excision with negative margins was made and the defect was
      reconstructed with a titanium plate. Subsequently, the lesion was
      histopathologically diagnosed as an angiolipoma of the frontal bone. The
      postoperative period was uneventful and she remained well during 1-year follow-up
      with no evidence of recurrence. Angiolipomas are rare benign lipomatous lesions
      located mostly in subcutaneous tissue of the forearm or trunk and frequently
      occur before puberty or in young adults. They are not common in bones. To the
      best of our knowledge, this is the first angiolipoma of the frontal bone
      reported. 

PMID- 24943773
TI  - Granular cell ameloblastoma of mandible.
AB  - Ameloblastoma is a neoplasm of odontogenic epithelium, especially of enamel organ
      type tissue that has not undergone differentiation to the point of hard tissue
      formation. Granular cell ameloblastoma is a rare condition, accounting for 3-5%
      of all ameloblastoma cases. A 30-year-old female patient presented with the chief
      complaint of swelling at the right lower jaw region since 1 year.
      Orthopantomogram and computed tomography scan was suggestive of primary bone
      tumor. Histopathologically, diagnosis of granular cell ameloblastoma of right
      mandible was made. 

PMID- 24943774
TI  - Intramedullary meningioma of spinal cord: case report of a rare tumor
      highlighting the differential diagnosis of spinal intramedullary neoplasms.
AB  - A 15-year-old male presented with progressive weakness of both lower limbs with
      urinary incontinence. Magnetic resonance imaging revealed a spinal intramedullary
      mass at D7-D8 level. The child was operated with a preliminary diagnosis of an
      intramedullary tumor. Atypical ependymoma and astrocytoma were considered in the
      differential diagnosis. Per- and post-operative histopathological examination
      reported the case as transitional meningioma (WHO Grade I). Spinal intramedullary
      meningiomas being a rare entity may be confused with other common intramedullary
      tumors. Though, rare still the possibility of an intramedullary spinal mass of
      being a meningioma does exist and therefore should be considered in the
      differential diagnosis of intramedullary tumors. 

PMID- 24943775
TI  - Primary chondrosarcoma of breast--cytology with histopathological correlation: a
      rare case report with review of literature.
AB  - Malignant mesenchymal tumors of the breast other than angiosarcoma are extremely
      rare and comprise <0.5% of breast tumors. Primary chondrosarcoma of the breast is
      an extremely rare entity and only 10 cases are reported as single case reports in
      literature until date. A diagnosis of primary mammary sarcoma can be established
      only after excluding metaplastic carcinomas and malignant phyllodes by extensive
      sampling for evidence of in situ or invasive carcinoma. Here, we report a primary
      chondrosarcoma of breast in a 55-year-old lady diagnosed precisely on fine-needle
      aspiration cytology and confirmed by histopathological examination after total
      mastectomy. We emphasize on diagnostic difficulties encountered in cytology
      smears and discuss differential diagnoses.

PMID- 24943776
TI  - Metachronous malignancies in head and neck region: report of two cases.
AB  - The development of a second primary cancer after treatment of the first with
      radiotherapy or chemotherapy is well documented. Multiple metachronous primary
      cancers are known to occur in an individual, but it is often seen with
      hematological malignancies of childhood. The prevalence of multiple primary
      malignancies (MPM) is between 0.73% and 11.7%. The most frequent malignant
      associations are ovary-colon, ovary-breast, and breast-breast. The possibility of
      developing a second metachronous cancer 5 years after undergoing treatment of the
      initial head and neck cancer is approximately 22%. Here, we report two cases of
      multiple metachronous malignancies in head and neck region. A 46-year-old woman
      presented with thyroid and salivary gland neoplasms metachronously and another 21
      year-old woman with Hodgkin' s Lymphoma, mucoepidermoid carcinoma of salivary
      Gland, and follicular variant of papillary carcinoma of thyroid. 

PMID- 24943777
TI  - Endometrioid carcinoma infiltrating atypical leiomyoma: a mimicker of malignant
      mixed Mullerian tumor.
AB  - Atypical or symplastic leiomyoma is a rare histological variant of leiomyoma.
      This is a case report of 63-year-old patient who underwent hysterectomy with
      bilateral salpingo-oophorectomy. Histopathology of the polypoid growth seen in
      the endometrial cavity revealed atypical leiomyoma infiltrated by endometrioid
      cancer. Atypical leiomyoma can be misdiagnosed as leiomyosarcoma. Thus,
      carcinosarcoma was ruled out as it has an ominous prognosis. A diagnosis of
      atypical leiomyoma infiltrated by endometrioid cancer was given. We report this
      case as there are very few case reports of the above two pathology occurring
      simultaneously in the same patient. 

PMID- 24943778
TI  - Plasmacytoid urothelial carcinoma of the bladder.
AB  - Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is an uncommon and
      aggressive variant of urothelial carcinoma associated with late presentation and
      poor prognosis. Immunohistochemical examination showing expression of epithelial
      markers, CD138, and losing the membranous expression of E-cadherin confirms
      evidence of PUC. Here, we report a case of bladder PUC of a 74-year-old male who
      presented with hematuria. A transurethral biopsy revealed urothelial carcinoma
      with plasmacytoid appearance. The diagnostic dilemmas of this unusual variant of
      urothelial malignancy and its clinical impact are discussed. The pathological
      diagnosis was PUC (High-grade, pT4N2M0) with diffuse muscle, small tracts, and
      vascular invasion, in which almost of the areas studied on the tissue section
      showed Plasmacytoid differentiation. 

PMID- 24943779
TI  - Solitary plasmacytoma of the metacarpal bone in an adolescent.
AB  - Solitary plasmacytoma of the bone (SPB) is a plasma cell neoplasm that usually
      presents as a lytic lesion mainly localized within the axial skeleton. The
      occurrence of SPB in young individuals is exceedingly rare, but has been
      sporadically reported before. We report a case of SPB involving metacarpal bone
      in a 16-year-old male with a prior history of trauma at the same site. 

PMID- 24943780
TI  - Enteropathy associated T cell lymphoma-monomorphic variant, presenting as
      bilateral ovarian masses.
AB  - Enteropathy associated T cell lymphoma (EATL) is a rare type of T-cell lymphoma,
      often associated with a history of celiac disease. It usually arises in the
      jejunum, but can involve other gastrointestinal tract sites such as stomach and
      colon. Monomorphic variant of EATL often occurs without a history of celiac
      disease, has variable histologic evidence of enteropathy, and is usually CD56 +.
      We report a case of EATL in a 49-year-old female presenting as bilateral ovarian
      masses. The morphology and immunophenotypic features were compatible with
      monomorphic variant of EATL.

PMID- 24943781
TI  - Inferior vena cava thrombosis in a case of amoebic liver abscess: is
      hypercomplementemia responsible for this rare entity?
AB  - Among the liver abscesses, thrombosis of the inferior vena cava (IVC) has been
      reported mainly in amoebic liver abscess (ALA) caused by Entamoeba histolytica
      (E.H). It is an unusual complication especially in paediatric age group.
      Association of hypercomplementemia and IVC thrombosis has not been discussed
      previously. Published data suggest that E.H can activate the complement system
      and can cause hypercomplementemia. A very few studies suggest that complement
      activation and hypercomplementemia are associated with thrombus formation. We
      describe a paediatric case of ALA complicated by IVC thrombosis extending to the
      right atrium and discuss the possible role of hypercomplementemia in causation of
      IVC thrombosis in cases of ALA. 

PMID- 24943782
TI  - Central nervous system nocardiosis with granulomatous pachymeningitis and
      osteomyelitis of skull vault.
AB  - A 34-year-old immunocompetent man weighing 95 kg was operated for a small left
      parietal scalp swelling in the year 2002. He was well until 2008, when he
      developed chronic diffuse headache, vomiting and drowsiness. The left parietal
      dura and overlying vault biopsy showed evidence of granulomatous pachymeningitis
      with osteomyelitis secondary to nocardiosis. He had responded well to inadequate
      antibiotic therapy. After a dormant period of 3 years, there was recrudescence of
      severe raised intracranial tension symptoms in 2011. Magnetic resonance imaging
      showed diffuse pachymeningeal thickening mainly involving the occipital dura,
      posterior falx, and tentorium cerebelli. In addition, well-defined small nodules
      with hypointense signals on both T1- and T2-weighted images were seen in
      occipital lobes. Patient was treated with three drug regime with good recovery at
      3 months follow-up. This is a rare case of central nervous system nocardiosis
      with skull vault osteomyelitis and a protracted clinical course. 

PMID- 24943783
TI  - Mycobacterium chelonae causing chronic wound infection and abdominal incisional
      hernia.
AB  - Mycobacterium chelonae is a rapidly growing mycobacterium that is found all over
      the environment, including sewage and tap water. They are important species
      associated with chronic non-healing wounds. We report a case in a 41 year old
      female patient who underwent multiple surgeries for an ovarian cyst, tubo-ovarian
      abscesses with peritonitis and a repair of an abdominal incisional hernia. 

PMID- 24943784
TI  - Myospherulosis in the nose: a report of an unusual lesion.

PMID- 24943787
TI  - Adenocarcinoma arising in tailgut cyst: a rare case.

PMID- 24943788
TI  - A rare case of neurofibroma with lipomatous differentiation and floret like giant
      cells-cytologically disguising as pleomorphic lipoma.

PMID- 24943789
TI  - Chondroid syringoma with extensive osseous differentiation: a rare finding.

PMID- 24943790
TI  - Basaloid carcinoma: rare human papillomavirus-related variant of squamous cell
      carcinoma of the anorectum: a case report.

PMID- 24943791
TI  - Bilateral ovarian serous cystadenofibromas coexisting with an incidental
      unilateral Brenner tumor and Walthard cell rests in bilateral Fallopian tubes: an
      unusual case with diagnostic implications and histogenesis.

PMID- 24943792
TI  - Calcific uremic arteriolopathy induced breast necrosis masquerading as breast
      cancer.

PMID- 24943793
TI  - Angiokeratoma circumscriptum: dilemma in diagnosis.

PMID- 24943794
TI  - Recurrent mucoepidermoid carcinoma of the left lower eyelid: a common tumor in a
      rare site.

PMID- 24943795
TI  - Hospital transfusion committee: role and responsibilities.

PMID- 24943796
TI  - Post traumatic abscess caused by Brevundimonas diminuata: a rare case report.

PMID- 24943797
TI  - A modified fungal slide culture technique.

PMID- 24943798
TI  - Mediastinal mass: arteriovenous malformation.

PMID- 24943801
TI  - Ticks of Australia. The species that infest domestic animals and humans.
AB  - The book Australian Ticks by F.H.S. Roberts (1970) is a land-mark in Australian
      tick biology. But it is time for a new and improved book on the ticks of
      Australia. The present book has identification guides and accounts of the biology
      and diseases associated with the 16 species of ticks that may feed on domestic
      animals and humans in Australia. These comprise five argasid (soft) ticks: Argas
      persicus (poultry tick), Argas robertsi (Robert's bird tick), Ornithodoros
      capensis (seabird soft tick), O. gurneyi (kangaroo soft tick), Otobius megnini
      (spinose ear tick); and 11 ixodid (hard) ticks, Amblyomma triguttatum (ornate
      kangaroo tick), Bothriocroton auruginans (wombat tick), B. hydrosauri (southern
      reptile tick), Haemaphysalis bancrofti (wallaby tick), H. longicornis (bush
      tick), Ixodes cornuatus (southern paralysis tick), I. hirsti (Hirst's marsupial
      tick), I. holocyclus (paralysis tick), I. tasmani (common marsupial tick),
      Rhipicephalus (Boophilus) australis (Australian cattle tick) and R. sanguineus
      (brown dog tick).  We use an image-matching system to identify ticks, much like
      the image-matching systems used in field-guides for birds and flowers. Ticks may
      be identified by drawings that emphasise unique matrices of uniformly defined
      morphological characters that, together, allow these 16 ticks to be identified by
      morphology unequivocally. The species accounts have seven sections: (i) General;
      (ii)  Differential diagnosis; (iii) Hosts; (iv) Life-cycle and seasonality; (v)
      Disease; (vi) Habitat and geographic distribution; (vii) Genes and genomes; and
      (viii) Other information. There are 71 figures and tables, including a glossary
      character matrices, drawings of life-cycles, drawings of genera, species, and
      colour photographs of tick biology. 

PMID- 24943802
TI  - The Higher Classification of the Ant Subfamily Ponerinae (Hymenoptera:
      Formicidae), with a Review of Ponerine Ecology and Behavior.
AB  - The tribal and generic classification of the diverse ant subfamily Ponerinae
      (Hymenoptera: Formicidae) is revised to reflect recent molecular phylogenetic
      information and a reappraisal of ponerine morphological diversity. The
      monogeneric tribe Thaumatomyrmecini (Thaumatomyrmex) is newly synonymized under
      Ponerini (syn. nov.), and the diverse genus Pachycondyla is fragmented into 19
      genera, largely along the lines of its junior synonyms: Bothroponera,
      Brachyponera (gen. rev.), Ectomomyrmex (gen. rev.), Euponera (gen. rev.),
      Hagensia (gen. rev.), Megaponera (gen. rev.), Mesoponera (gen. rev.), Neoponera
      (gen. rev.), Ophthalmopone (gen. rev.), Pachycondyla, Paltothyreus (gen. rev.),
      Pseudoneoponera (gen. rev.), Pseudoponera (gen. rev.), and 6 new genera:
      Austroponera (gen. nov.), Buniapone (gen. nov.), Fisheropone (gen. nov.),
      Mayaponera (gen. nov.), Parvaponera (gen. nov.) and Rasopone (gen. nov.). Some
      junior synonyms of Pachycondyla are transferred to junior synonym status under
      other genera: Wadeura as a junior synonym of Cryptopone (syn. nov.), and both
      Termitopone and Syntermitopone as junior synonyms of Neoponera (syn. nov.). A new
      genus, Iroponera (gen. nov.), based on the new species Iroponera odax (sp. nov.),
      is described from Australia. Molecular and morphological justifications for these
      taxonomic changes are given alongside discussions of phylogenetic relationships.
      Keys to the world genera of Ponerinae are provided, and morphological diagnoses
      and species lists are given for each genus. Finally, the available information on
      ponerine ecology and behavior is reviewed and synthesized.

PMID- 24943800
TI  - Disease modeling using human induced pluripotent stem cells: lessons from the
      liver.
AB  - Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any
      of the hundreds of distinct cell types that comprise the human body. This unique
      characteristic has resulted in considerable interest in the field of regenerative
      medicine, given the potential for these cells to be used to protect, repair, or
      replace diseased, injured, and aged cells within the human body. In addition to
      their potential in therapeutics, hPSCs can be used to study the earliest stages
      of human development and to provide a platform for both drug screening and
      disease modeling using human cells. Recently, the description of human induced
      pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to
      become far more accessible and physiologically relevant, as pluripotent cells can
      be generated from patients of any genetic background. Disease models derived from
      hIPSCs that manifest cellular disease phenotypes have been established to study
      several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based
      drug screens to investigate complex diseases for which the underlying genetic
      mechanism is unknown. As a result, the use of stem cells as research tools has
      seen an unprecedented growth within the last decade as researchers look for in
      vitro disease models which closely mimic in vivo responses in humans. Here, we
      discuss the beginnings of hPSCs, starting with isolation of human embryonic stem
      cells, moving into the development and optimization of hIPSC technology, and
      ending with the application of hIPSCs towards disease modeling and drug screening
      applications, with specific examples highlighting the modeling of inherited
      metabolic disorders of the liver. This article is part of a Special Issue
      entitled Linking transcription to physiology in lipodomics. 

PMID- 24943803
TI  - The shallow-water New Caledonia Drilliidae of genus Clavus Montfort, 1810
      (Mollusca: Gastropoda: Conoidea).
AB  - Species of the genus Clavus of the conoidean family Drilliidae that occur in the
      littoral and shallow waters of New Caledonia are here revised. This study is
      based primarily on recent expedition material from the Institut de Recherche pour
      le Developpement (New Caledonia) and Museum National d'Histoire Naturelle
      (France). A total of 22 species is recorded, of which eight are described as new.
      New species: Clavus boucheti, Clavus delphineae, Clavus virginieae, Clavus
      picoides, Clavus squamiferus, Clavus devexistriatus, Clavus hylikos, Clavus
      maestratii; New synonyms: Tylotiella Habe, 1958 = Clavus; Clavus leforestieri
      Hervier, 1896 = Pleurotoma obliquicostata Reeve, 1845; Pleurotoma mariei Crosse,
      1869 = Pleurotoma lamberti Montrouzier, 1860; Clavus mighelsi Kay, 1979, new name
      for Pleurotoma acuminata Mighels, 1845, non J. Sowerby, 1816, was misidentified
      by Kay 1979; the lectotype of P. acuminata Mighels, 1845, is mangeliine. Clavus
      mighelsi sensu Kay 1979, is a synonym of Pleurotoma humilis E. A. Smith, 1879. It
      is suggested that Pleurotoma pulchella Reeve, 1845, sometimes treated as an Indo
      Pacific species, may be a senior synonym of Fenimorea halidorema Schwengel, 1940,
      from the tropical western Atlantic. Nomen dubium: Pleurotoma mediocris Deshayes,
      1863.

PMID- 24943804
TI  - Revision of the genus Pelecinobaccha Shannon, description of Relictanum gen.
      nov., and redescription of Atylobaccha flukiella (Curran, 1941) (Diptera:
      Syrphidae).
AB  - Recent phylogenetic analyses of Ocyptamus Macquart, 1834 (Diptera, Syrphidae)
      confirmed the paraphyly of this genus and provided evidence to divide it into
      several monophyletic subgroups, of which the largest is the clade traditionally
      treated as the Ocyptamus tristis species group. This group is here redefined,
      divided into the genera Pelecinobaccha Shannon, 1927 and Relictanum gen. nov.,
      and revised along with the closely related and newly resurrected genus
      Atylobaccha Hull, 1949. Twenty-four new species (22 in Pelecinobaccha and two in
      Relictanum) are described and 35 species (27 in Pelecinobaccha, seven in
      Relictanum and Atylobaccha flukiella Curran, 1941) are redescribed.
      Pelecinobaccha is divided into four species groups (P. adspersa species group, P.
      brevipennis species group, P. peruviana species group and P. susio species
      group). An identification key, illustrations and distribution maps for all
      species from this study are also presented.

PMID- 24943805
TI  - Torrenticolid water mites (Acari: Hydrachnidia: Torrenticolidae) from Ghana.
AB  - New records of water mites of the family Torrenticolidae (Acari: Hydrachnidia)
      from streams in Ghana are presented. One new subgenus, Vietsclio n. subgen., is
      erected to accommodate Monatractides uniscutatus (K. Viets, 1925), characterized
      by the presence of swimming setae on leg II-IV. Seven new species are described:
      Neoatractides (Allotorrenticola) erato n. sp., Monatractides (Monatractides)
      euterpe n. sp., M. (M.) melpomene n. sp., M. (M.) polyhymnia n. sp., M. (M.)
      thalia n. sp., M. (M.) terpsichore n. sp., M. (M.) urania n. sp. Torrenticola
      calliope is established as the new name for previously reported populations of T.
      harrisoni K. Viets, 1956 from Ethiopia. The first description of the female is
      given for Monatractides (Monatractides) acutiscutatus (K. Viets, 1914) and M.
      (Vietsclio) uniscutatus K. Viets 1925. The subgenus Allotorrenticola Cook, 1967,
      previously known only from Asia, is reported for the first time from the
      Afrotropical region. Additionally, first records for Ghana are given for
      Torrenticola anomallela Cook, 1966, T. bomiensis Cook, 1966, T. fasciata (K.
      Viets, 1916), T. motasi Cook, 1966, T. harrisoni K. Viets, 1956,
      Pseudotorrenticola mitchelli Cook, 1966, Monatractides (Monatractides)
      acutiscutatus (K. Viets, 1914), M. (M.) convexiscutata (K. Viets, 1958), M. (M.)
      koenikei (K. Viets, 1916), M. (M.) stigeophora (Cook, 1966), M. (M.) ventriosus
      (K. Viets, 1916), M. (M.) microstoma Koenike, 1898-species complex, and M.
      uniscutatus (K. Viets 1925).

PMID- 24943806
TI  - Amphiphilic phthalocyanine-cyclodextrin conjugates for cancer photodynamic
      therapy.
AB  - Three phthalocyanines (Pcs) conjugated with alpha-, beta- and gamma-cyclodextrins
      (CDs) were prepared and their application as photosensitizer (PS) agents was
      assessed by photophysical, photochemical and in vitro photobiological studies.
      The photoactivity of Pc-alpha-CD and Pc-gamma-CD ensures their potential as PDT
      drugs against UM-UC-3 human bladder cancer cells.

PMID- 24943807
TI  - Hobson's choice two-stage hepatectomy for multiple and bilobar colorectal liver
      metastases with portal vein embolization: report of two cases.
AB  - Liver resection is recognized as the preferred treatment for patients with
      colorectal liver metastases (CLM) because it offers long-term survival; it is the
      only hope for a cure. However, in the majority of cases, liver surgery is
      contraindicated due to the small volume of the future remnant liver. To extend
      the surgical indications for CLM, a planned two-stage hepatectomy procedure with
      portal vein embolization (PVE) was developed specifically for patients with
      multiple and bilobar CLM. The rationale for performing the procedure was a
      concern about the possible overgrowth of intrafuture remnant liver lesions
      following PVE, and it was therefore recommended for all multiple bilobar CLM
      cases, even when one-stage hepatectomy was technically feasible. We recently
      performed Hobson's choice two-stage hepatectomy in two cases for reasons
      different from those of the original planned two-stage hepatectomy. In the
      present report, we describe our Hobson's choice two-stage hepatectomy strategy,
      which provided favorable short-term outcomes. 

PMID- 24943808
TI  - Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood.
AB  - BACKGROUND: Evidence on the association between post-natal exposure to
      antibiotics and the development of asthma is extensive, but inconsistent and even
      less is known about prenatal exposure. OBJECTIVE: The aim of this study was to
      examine the associations between prenatal and post-natal exposure to different
      antibiotics and the risk of childhood asthma in a population- and register-based
      nested case-control study. METHODS: All children who were born in 1996-2004 in
      Finland and diagnosed with asthma by 2006 were identified from a national health
      register. For each case, one matched control was selected. Information on asthma
      diagnoses, purchased anti-asthmatic drugs and antibiotics as well as putative
      confounders was obtained from national health registries. The associations were
      analysed using conditional logistic regression for children diagnosed at the age
      of 3 years or later (n = 6 690 case-control pairs). RESULTS: Maternal use of any
      antibiotics during pregnancy was associated with an increased risk of asthma in
      the offspring [adjusted odds ratio (OR) = 1.31 (95% confidence interval (CI):
      1.21-1.42)]. Several maternal specific antibiotics were associated with the risk
      of asthma, and the strongest association was observed for cephalosporins [OR =
      1.46 (95% CI 1.30-1.64)]. Child's use of antibiotics during the first year of
      life was associated with an increased risk of asthma [OR = 1.60 (95% CI 1.48
      1.73)]. Child's use of cephalosporins [OR = 1.79 (95% CI 1.59-2.01)],
      sulphonamides and trimethoprim [OR = 1.65 (95% CI 1.34-2.02)], macrolides [OR =
      1.61 (95% CI 1.46-1.78)] and amoxicillin [OR = 1.46 (95% CI 1.35-1.58)] was
      associated with an increased risk of asthma. CONCLUSIONS AND CLINICAL RELEVANCE:
      Both prenatal and post-natal exposure to antibiotics was associated with an
      increased risk of asthma. The potential role of adverse effects of antibiotics on
      the gut microbiota and the development of asthma should be further explored.

PMID- 24943809
TI  - Qualitative analysis of seized cocaine samples using desorption electrospray
      ionization- mass spectrometry (DESI-MS).
AB  - Desorption electrospray ionization - mass spectrometry (DESI-MS) is a useful
      technique for the qualitative analysis of compounds found in seized drug
      material. In this study, DESI-MS was utilized in the screening analysis of
      illicit cocaine samples. The technique was also applied to the geographical
      origin determination of these samples. The limit of detection was determined to
      be 24.3 ug (or 3.47 ug/mm(2) ) and the analysis time was less than 1 minute per
      sample. The intra-day and inter-day precision for the detection of cocaine was 11
      % and 42 %, respectively; therefore the quantitative data provided by DESI-MS was
      limited in its use for accurate determination of cocaine concentration in a
      sample. Using the quadrupole time-of-flight (QTOF) mass spectrometer, the
      presence of cocaine and impurities detected were confirmed by accurate tandem MS
      data. The qualitative chemical profiles obtained using DESI-MS were compared to
      two popular analysis techniques, GC-MS and LC-MS. The effects of a range of
      adulterants including caffeine, procaine, levamisole, lignocaine, paracetamol,
      and atropine on the detectability of cocaine were also investigated. It was found
      that the addition of these adulterants in a cocaine sample did not prevent the
      detection of the analyte itself (there was slight enhancement in some samples),
      which was useful in drug detection. The detection of truxillines in the seized
      samples by DESI-MS aided in the preliminary determination of geographical origin,
      i.e., Bolivian, Peruvian or Colombian leaf origin. The application of DESI-MS to
      the qualitative analysis and screening of seized cocaine samples demonstrates the
      potential and applicability of the technique to the fast chemical profiling of
      illicit samples.

PMID- 24943810
TI  - Immunotherapy: Two hits are better than one.

PMID- 24943812
TI  - Tumour cell invasion: an emerging role for basal epithelial cell extrusion.
AB  - Metastasis is the leading cause of cancer-related deaths, but it is unclear how
      cancer cells escape their primary sites in epithelia and disseminate to other
      sites in the body. One emerging possibility is that transformed epithelial cells
      could invade the underlying tissue by a process called cell extrusion, which
      epithelia use to remove cells without disrupting their barrier function.
      Typically, during normal cell turnover, live cells extrude apically from the
      epithelium into the lumen and later die by anoikis; however, several oncogenic
      mutations shift cell extrusion basally, towards the tissue that the epithelium
      encases. Tumour cells with high levels of survival and motility signals could use
      basal extrusion to escape from the tissue and migrate to other sites within the
      body.

PMID- 24943813
TI  - Effects of three fire-suppressant foams on the germination and physiological
      responses of plants.
AB  - Suppressant foams used to fight forest fires may leave residual effects on
      surviving biota that managers need to consider prior to using them. We examined
      how three fire-suppressant foams (FSFs) (Forexpan S, Phos-Chek-WD881, and Silv
      ex) affected seed germination and physiological responses of three plant species.
      Exposure to FSFs, whether in diluted concentrations or those typical in the
      field, reduced final germination percentages of seeds grown in petri dishes and
      within growth chambers. However, the FSFs did not cause total germination failure
      in any treatment. Inhibition of germination increased with longer exposure times,
      but only to diluted FSF solutions. Unlike in the laboratory experiments, none of
      the three FSFs affected seedling emergence when tested in field conditions.
      Further, we found no evidence of long-term phytotoxic effects on antioxidant
      enzyme activity nor chlorophyll content of the plant saplings. Therefore,
      although the three FSFs showed evidence of phytotoxicity to plants in laboratory
      tests, their actual impact on terrestrial ecosystems may be minimal. We suggest
      that the benefits of using these FSFs to protect plants in threatened forest
      ecosystems outweigh their minor risks.

PMID- 24943814
TI  - Application of a three-dimensional water quality model as a decision support tool
      for the management of land-use changes in the catchment of an oligotrophic lake.
AB  - While expansion of agricultural land area and intensification of agricultural
      practices through irrigation and fertilizer use can bring many benefits to
      communities, intensifying land use also causes more contaminants, such as
      nutrients and pesticides, to enter rivers, lakes, and groundwater. For lakes such
      as Benmore in the Waitaki catchment, South Island, New Zealand, an area which is
      currently undergoing agricultural intensification, this could potentially lead to
      marked degradation of water clarity as well as effects on ecological,
      recreational, commercial, and tourism values. We undertook a modeling study to
      demonstrate science-based options for consideration of agricultural
      intensification in the catchment of Lake Benmore. Based on model simulations of a
      range of potential future nutrient loadings, it is clear that different areas
      within Lake Benmore may respond differently to increased nutrient loadings. A
      western arm (Ahuriri) could be most severely affected by land-use changes and
      associated increases in nutrient loadings. Lake-wide annual averages of an
      eutrophication indicator, the trophic level index (TLI) were derived from
      simulated chlorophyll a, total nitrogen, and total phosphorus concentrations.
      Results suggest that the lake will shift from oligotrophic (TLI = 2-3) to
      eutrophic (TLI = 4-5) as external loadings are increased eightfold over current
      baseline loads, corresponding to the potential land-use intensification in the
      catchment. This study provides a basis for use of model results in a decision
      making process by outlining the environmental consequences of a series of land
      use management options, and quantifying nutrient load limits needed to achieve
      defined trophic state objectives.

PMID- 24943827
TI  - Estimating health state utility values from discrete choice experiments--a QALY
      space model approach.
AB  - Using discrete choice experiments (DCEs) to estimate health state utility values
      has become an important alternative to the conventional methods of Time Trade-Off
      and Standard Gamble. Studies using DCEs have typically used the conditional logit
      to estimate the underlying utility function. The conditional logit is known for
      several limitations. In this paper, we propose two types of models based on the
      mixed logit: one using preference space and the other using quality-adjusted life
      year (QALY) space, a concept adapted from the willingness-to-pay literature.
      These methods are applied to a dataset collected using the EQ-5D. The results
      showcase the advantages of using QALY space and demonstrate that the preferred
      QALY space model provides lower estimates of the utility values than the
      conditional logit, with the divergence increasing with worsening health states.

PMID- 24943811
TI  - Imaging preclinical tumour models: improving translational power.
AB  - Recent developments and improvements of multimodal imaging methods for use in
      animal research have substantially strengthened the options of in vivo
      visualization of cancer-related processes over time. Moreover, technological
      developments in probe synthesis and labelling have resulted in imaging probes
      with the potential for basic research, as well as for translational and clinical
      applications. In addition, more sophisticated cancer models are available to
      address cancer-related research questions. This Review gives an overview of
      developments in these three fields, with a focus on imaging approaches in animal
      cancer models and how these can help the translation of new therapies into the
      clinic. 

PMID- 24943828
TI  - Functional characterization of terpene synthases and chemotypic variation in
      three lavender species of section Stoechas.
AB  - Lavandula pedunculata (Mill.) Cav. subsp. lusitanica, Lavandula stoechas L.
      subsp. stoechas and Lavandula viridis l'Her. are three lavender taxa that belong
      to the botanical section Stoechas and are widely used as aromatherapy, culinary
      herb or folk medicine in many Mediterranean regions. The analysis of their
      bioactive volatile constituents revealed the presence of 124 substances, the most
      abundant being the bicyclic monoterpenes fenchone, camphor and 1,8-cineole that
      give these three species their respective chemotypes. Most noteworthy was
      fenchone which, with its reduced form fenchol, made 48% of the total volatile
      constituents of L. pedunculata while present at 2.9% in L. stoechas and
      undetectable in L. viridis. In order to provide a molecular explanation to the
      differences in volatile compounds of these three species, two monoterpene
      synthases (monoTPS) and one sesquiterpene synthase (sesquiTPS) were cloned in L.
      pedunculata and functionally characterized as fenchol synthase (LpFENS), alpha
      pinene synthase (LpPINS) and germacrene A synthase (LpGEAS). The two other
      lavender species contained a single orthologous gene for each of these three
      classes of TPS with similar enzyme product specificities. Expression profiles of
      FENS and PINS genes matched the accumulation profile of the enzyme products
      unlike GEAS. This study provides one of the rare documented cases of chemotype
      modification during plant speciation via changes in the level of plant TPS gene
      expression, and not functionality. 

PMID- 24943830
TI  - Psychosurgery for drug addiction.

PMID- 24943829
TI  - A universal harm-minimisation approach to preventing psychostimulant and cannabis
      use in adolescents: a cluster randomised controlled trial.
AB  - BACKGROUND: Psychostimulants and cannabis are two of the three most commonly used
      illicit drugs by young Australians. As such, it is important to deliver
      prevention for these substances to prevent their misuse and to reduce associated
      harms. The present study aims to evaluate the feasibility and effectiveness of
      the universal computer-based Climate Schools: Psychostimulant and Cannabis
      Module. METHODS: A cluster randomised controlled trial was conducted with 1734
      Year 10 students (mean age = 15.44 years; SD = 0.41) from 21 secondary schools in
      Australia. Schools were randomised to receive either the six lesson computer
      based Climate Schools program or their usual health classes, including drug
      education, over the year. RESULTS: The Climate Schools program was shown to
      increase knowledge of cannabis and psychostimulants and decrease pro-drug
      attitudes. In the short-term the program was effective in subduing the uptake and
      plateauing the frequency of ecstasy use, however there were no changes in
      meth/amphetamine use. In addition, females who received the program used cannabis
      significantly less frequently than students who received drug education as usual.
      Finally, the Climate Schools program was related to decreasing students'
      intentions to use meth/amphetamine and ecstasy in the future, however these
      effects did not last over time. CONCLUSIONS: These findings provide support for
      the use of a harm-minimisation approach and computer technology as an innovative
      platform for the delivery of prevention education for illicit drugs in schools.
      The current study indicated that teachers and students enjoyed the program and
      that it is feasible to extend the successful Climate Schools model to the
      prevention of other drugs, namely cannabis and psychostimulants. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12613000492752.

PMID- 24943831
TI  - Structure-based design of new KSP-Eg5 inhibitors assisted by a targeted
      multicomponent reaction.
AB  - An integrated multidisciplinary approach that combined structure-based drug
      design, multicomponent reaction synthetic approaches and functional
      characterization in enzymatic and cell assays led to the discovery of new kinesin
      spindle protein (KSP) inhibitors with antiproliferative activity. A focused
      library of new benzimidazoles obtained by a Ugi+Boc removal/cyclization reaction
      sequence generated low-micromolar-range KSP inhibitors as promising anticancer
      prototypes. The design and functional studies of the new chemotypes were assessed
      by computational modeling and molecular biology techniques. The most active
      compounds-20 (IC50 =1.49 MUM, EC50 =3.63 MUM) and 22 (IC50 =1.37 MUM, EC50 =6.90
      MUM)-were synthesized with high efficiency by taking advantage of the
      multicomponent reactions. 

PMID- 24943834
TI  - Overexpression of CDKN2B (p15INK4B) and altered global DNA methylation status in
      mesenchymal stem cells of high-risk myelodysplastic syndromes.

PMID- 24943832
TI  - Recurrent mutations refine prognosis in chronic lymphocytic leukemia.
AB  - Through the European Research Initiative on chronic lymphocytic leukemia (CLL)
      (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1
      (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes,
      mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%)
      were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12,
      whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1
      and TP53 exhibited variable frequencies and were mostly enriched within
      clinically aggressive cases. Interestingly, as the timespan between diagnosis and
      mutational screening increased, so too did the incidence of SF3B1 mutations; no
      such increase was observed for NOTCH1 mutations. Regarding the clinical impact,
      NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation,
      TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889
      treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1
      mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations,
      retained independent significance. Importantly, TP53ab and SF3B1 mutations had an
      adverse impact even in U-CLL. In conclusion, we support the clinical relevance of
      novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and
      TP53 mutations, even independent of IGHV mutational status, thus underscoring the
      need for urgent standardization/harmonization of the detection methods. 

PMID- 24943835
TI  - Never too old for an autogenous dialysis fistula? Results of endovascular
      interventions in nonagenarians.
AB  - The number of elderly patients in hemodialysis has increased in recent years and
      nowadays there are significant numbers of nonagenarians. However, there is
      currently no information in the literature about arteriovenous fistula (AVF)
      outcomes in patients aged over 90 years after endovascular treatment for stenosis
      or thrombosis. This retrospective analysis of prospectively collected data
      included 38 consecutive patients aged over 90 years who were referred for
      endovascular evaluation and treatment of AVF nonmaturation (n = 11), dysfunction
      (n = 25), or thrombosis (n = 2) between 2005 and 2013. Median age was 93.9 years,
      and 24% were diabetic and 47% hypertensive patients. Immature and dysfunctional
      AVFs were treated by angioplasty, thrombosed fistulas by thromboaspiration.
      Fistula patency rates were calculated according to the Life-Table method. The
      immediate overall clinical success rate was 97.4%. Complications included four
      transient dilation-induced ruptures. Stents were placed for rupture control (n =
      3) and major elastic recoil (n = 3), and to rectify a basilic vein pseudoaneurysm
      developed after dilation. Mean follow-up was 62.6 months. Primary patency rates
      were 60% and 43% at 1 and 2 years, respectively. Secondary patency rates were 95%
      and 92% at 1 and 2 years, respectively. Patency rates were not significantly
      different between immature and dysfunctional AVFs. Endovascular treatment of AVF
      complications appears to be a valuable approach in nonagenarian patients in view
      of the low invasiveness, low complication rate, and relatively good long-term
      patency rates.

PMID- 24943833
TI  - IgM peak independently predicts treatment-free survival in chronic lymphocytic
      leukemia and correlates with accumulation of adverse oncogenetic events.
AB  - We examined the significance of IgM peaks in chronic lymphocytic leukemia (CLL),
      including its association with newly reported MYD88, BIRC3, NOTCH1 and SF3B1
      mutations. A total of 27, 25, 41 and 57 patients with monoclonal IgM or IgG peaks
      (IgM and IgG groups), hypogammaglobulinemia (Hypo-gamma group) and normal
      immunoglobulin serum levels (normal-gamma group) were, respectively, included.
      IgM peaks were mainly associated with Binet stage C and the del(17p). Biased
      usage of IGHV3-48 was shared by both IgM and IgG groups. IGHV3-74 and IGHV4-39
      gene rearrangements were specific for IgM and IgG peaks, respectively. SF3B1,
      NOTCH1, MYD88 and BIRC3 mutation frequencies were 12%, 4%, 2% and 2%,
      respectively, being over-represented in IgM, IgG and Hypo-gamma groups for SF3B1,
      and being equal between normal-gamma and IgM groups for MYD88. Overall, 76%, 87%,
      49% and 42% of cases from IgM, IgG, Hypo-gamma and normal-gamma groups had at
      least one intermediate or poor prognosis genetic marker, respectively. By
      multivariate analysis, IgM peaks were associated with shorter treatment-free
      survival independently from any other univariate poor prognosis biological
      parameters, including IgG peaks, Hypo-gamma, IGHV status, SF3B1 mutations,
      cytogenetics and lymphocytosis. Therefore, as with IgG peaks, IgM peaks
      aggravated the natural course of CLL, with increased accumulation of adverse
      genetic events. 

PMID- 24943836
TI  - Molecular basis of thyrotropin and thyroid hormone action during implantation and
      early development.
AB  - BACKGROUND: Implantation and early embryo development are finely regulated
      processes in which several molecules are involved. Evidence that thyroid hormones
      (TH: T4 and T3) might be part of this machinery is emerging. An increased demand
      for TH occurs during gestation, and any alteration in maternal thyroid physiology
      has significant implications for both maternal and fetal health. Not only overt
      but also subclinical hypothyroidism is associated with infertility as well as
      with obstetric complications, including disruptions and disorders of pregnancy,
      labor, delivery, and troubles in early neonatal life. METHODS: We searched the
      PubMed and Google Scholar databases for articles related to TH action on ovary,
      endometrium, trophoblast maturation and embryo implantation. In addition,
      articles on the regulation of TH activity at cellular level have been reviewed.
      The findings are hereby summarized and critically discussed. RESULTS: TH have
      been shown to influence endometrial, ovarian and placental physiology. TH
      receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors
      (TSHR) are widely expressed in the feto-maternal unit during implantation, and
      both the endometrium and the trophoblast might be influenced by TH either
      directly or through TH effects on the synthesis and activity of implantation
      mediating molecules. Interestingly, due to the multiplicity of mechanisms
      involved in TH action (e.g. differential expression of TR isoforms, heterodimeric
      receptor partners, interacting cellular proteins, and regulating enzymes), the TH
      concentration in blood is not always predictive of their cellular availability
      and activity at both genomic and nongenomic level. CONCLUSIONS: In addition to
      the known role of TH on the hormonal milieu of the ovarian follicle cycle, which
      is essential for a woman's fertility, evidence is emerging on the importance of
      TH signaling during implantation and early pregnancy. Based on recent
      observations, a local action of TH on female reproductive organs and the embryo
      during implantation appears to be crucial for a successful pregnancy.
      Furthermore, an imbalance in the spatio-temporal expression of factors involved
      in TH activity might induce early arrest of pregnancy in women considered as
      euthyroid, based on their hormonal blood concentration. In conclusion,
      alterations of the highly regulated local activity of TH may play a crucial,
      previously underestimated, role in early pregnancy and pregnancy loss. Further
      studies elucidating this topic should be encouraged.

PMID- 24943837
TI  - Nup50 is required for cell differentiation and exhibits transcription-dependent
      dynamics.
AB  - The nuclear pore complex (NPC) plays a critical role in gene expression by
      mediating import of transcription regulators into the nucleus and export of RNA
      transcripts to the cytoplasm. Emerging evidence suggests that in addition to
      mediating transport, a subset of nucleoporins (Nups) engage in transcriptional
      activation and elongation at genomic loci that are not associated with NPCs. The
      underlying mechanism and regulation of Nup mobility on and off nuclear pores
      remain unclear. Here we show that Nup50 is a mobile Nup with a pronounced
      presence both at the NPC and in the nucleoplasm that can move between these
      different localizations. Strikingly, the dynamic behavior of Nup50 in both
      locations is dependent on active transcription by RNA polymerase II and requires
      the N-terminal half of the protein, which contains importin alpha- and Nup153
      binding domains. However, Nup50 dynamics are independent of importin alpha,
      Nup153, and Nup98, even though the latter two proteins also exhibit transcription
      dependent mobility. Of interest, depletion of Nup50 from C2C12 myoblasts does not
      affect cell proliferation but inhibits differentiation into myotubes. Taken
      together, our results suggest a transport-independent role for Nup50 in chromatin
      biology that occurs away from the NPC. 

PMID- 24943838
TI  - Effects of high glucose on integrin activity and fibronectin matrix assembly by
      mesangial cells.
AB  - The filtration unit of the kidney is the glomerulus, a capillary network
      supported by mesangial cells and extracellular matrix (ECM). Glomerular function
      is compromised in diabetic nephropathy (DN) by uncontrolled buildup of ECM,
      especially type IV collagen, which progressively occludes the capillaries.
      Increased levels of the ECM protein fibronectin (FN) are also present; however,
      its role in DN is unknown. Mesangial cells cultured under high glucose conditions
      provide a model system for studying the effect of elevated glucose on deposition
      of FN and collagen IV. Imaging of mesangial cell cultures and analysis of
      detergent-insoluble matrix show that, under high glucose conditions, mesangial
      cells assembled significantly more FN matrix, independent of FN protein levels.
      High glucose conditions induced protein kinase C-dependent beta1 integrin
      activation, and FN assembly in normal glucose was increased by stimulation of
      integrin activity with Mn(2+). Collagen IV incorporation into the matrix was also
      increased under high glucose conditions and colocalized with FN fibrils. An
      inhibitor of FN matrix assembly prevented collagen IV deposition, demonstrating
      dependence of collagen IV on FN matrix. We conclude that high glucose induces FN
      assembly, which contributes to collagen IV accumulation. Enhanced assembly of FN
      might facilitate dysregulated ECM accumulation in DN. 

PMID- 24943839
TI  - A role for nuclear envelope-bridging complexes in homology-directed repair.
AB  - Unless efficiently and faithfully repaired, DNA double-strand breaks (DSBs) cause
      genome instability. We implicate a Schizosaccharomyces pombe nuclear envelope
      spanning linker of nucleoskeleton and cytoskeleton (LINC) complex, composed of
      the Sad1/Unc84 protein Sad1 and Klarsicht/Anc1/SYNE1 homology protein Kms1, in
      the repair of DSBs. An induced DSB associates with Sad1 and Kms1 in S/G2 phases
      of the cell cycle, connecting the DSB to cytoplasmic microtubules. DSB resection
      to generate single-stranded DNA and the ATR kinase drive the formation of Sad1
      foci in response to DNA damage. Depolymerization of microtubules or loss of Kms1
      leads to an increase in the number and size of DSB-induced Sad1 foci. Further,
      Kms1 and the cytoplasmic microtubule regulator Mto1 promote the repair of an
      induced DSB by gene conversion, a type of homology-directed repair. kms1
      genetically interacts with a number of genes involved in homology-directed
      repair; these same gene products appear to attenuate the formation or promote
      resolution of DSB-induced Sad1 foci. We suggest that the connection of DSBs with
      the cytoskeleton through the LINC complex may serve as an input to repair
      mechanism choice and efficiency. 

PMID- 24943840
TI  - An aspartyl cathepsin, CTH3, is essential for proprotein processing during
      secretory granule maturation in Tetrahymena thermophila.
AB  - In Tetrahymena thermophila, peptides secreted via dense-core granules, called
      mucocysts, are generated by proprotein processing. We used expression profiling
      to identify candidate processing enzymes, which localized as cyan fluorescent
      protein fusions to mucocysts. Of note, the aspartyl cathepsin Cth3p plays a key
      role in mucocyst-based secretion, since knockdown of this gene blocked
      proteolytic maturation of the entire set of mucocyst proproteins and dramatically
      reduced mucocyst accumulation. The activity of Cth3p was eliminated by mutation
      of two predicted active-site mutations, and overexpression of the wild-type gene,
      but not the catalytic-site mutant, partially rescued a Mendelian mutant defective
      in mucocyst proprotein processing. Our results provide the first direct evidence
      for the role of proprotein processing in this system. Of interest, both
      localization and the CTH3 disruption phenotype suggest that the enzyme provides
      non-mucocyst-related functions. Phylogenetic analysis of the T. thermophila
      cathepsins, combined with prior work on the role of sortilin receptors in
      mucocyst biogenesis, suggests that repurposing of lysosomal enzymes was an
      important step in the evolution of secretory granules in ciliates. 

PMID- 24943841
TI  - Maturation of late Golgi cisternae into RabE(RAB11) exocytic post-Golgi carriers
      visualized in vivo.
AB  - The mechanism(s) by which proteins traverse and exit the Golgi are incompletely
      understood. Using Aspergillus nidulans hyphae, we show that late Golgi cisternae
      undergo changes in composition to gradually lose Golgi identity while acquiring
      post-Golgi RabE(RAB11) identity. This behavior of late Golgi cisternae is
      consistent with the cisternal maturation model. Post-Golgi RabE(RAB11) carriers
      travel to, and accumulate at, the apex, indicating that fusion is rate limiting
      for exocytosis. These carriers, which are loaded with kinesin, dynein, and
      MyoE(MYO5), move on a microtubule-based bidirectional conveyor belt relaying them
      to actin, which ultimately focuses exocytosis at the apex. Dynein drags
      RabE(RAB11) carriers away if engagement of MyoE(MYO5) to actin cables fails.
      Microtubules seemingly cooperating with F-actin capture can sustain secretion if
      MyoE(MYO5) is absent. Thus, filamentous fungal secretion involving post-Golgi
      carriers is remarkably similar, mechanistically, to the transport of melanosomes
      in melanocyte dendrites, even though melanosome biogenesis involves lysosomes
      rather than Golgi.

PMID- 24943842
TI  - Mathematical model with spatially uniform regulation explains long-range
      bidirectional transport of early endosomes in fungal hyphae.
AB  - In many cellular contexts, cargo is transported bidirectionally along microtubule
      bundles by dynein and kinesin-family motors. Upstream factors influence how
      individual cargoes are locally regulated, as well as how long-range transport is
      regulated at the whole-cell scale. Although the details of local, single-cargo
      bidirectional switching have been extensively studied, it remains to be
      elucidated how this results in cell-scale spatial organization. Here we develop a
      mathematical model of early endosome transport in Ustilago maydis. We demonstrate
      that spatiotemporally uniform regulation, with constant transition rates, results
      in cargo dynamics that is consistent with experimental data, including data from
      motor mutants. We find that microtubule arrays can be symmetric in plus-end
      distribution but asymmetric in binding-site distribution in a manner that affects
      cargo dynamics and that cargo can travel past microtubule ends in microtubule
      bundles. Our model makes several testable predictions, including secondary
      features of dynein and cargo distributions. 

PMID- 24943843
TI  - Distinct fusion properties of synaptotagmin-1 and synaptotagmin-7 bearing dense
      core granules.
AB  - Adrenal chromaffin cells release hormones and neuropeptides that are essential
      for physiological homeostasis. During this process, secretory granules fuse with
      the plasma membrane and deliver their cargo to the extracellular space. It was
      once believed that fusion was the final regulated step in exocytosis, resulting
      in uniform and total release of granule cargo. Recent evidence argues for
      nonuniform outcomes after fusion, in which cargo is released with variable
      kinetics and selectivity. The goal of this study was to identify factors that
      contribute to the different outcomes, with a focus on the Ca(2+)-sensing
      synaptotagmin (Syt) proteins. Two Syt isoforms are expressed in chromaffin cells:
      Syt-1 and Syt-7. We find that overexpressed and endogenous Syt isoforms are
      usually sorted to separate secretory granules and are differentially activated by
      depolarizing stimuli. In addition, overexpressed Syt-1 and Syt-7 impose distinct
      effects on fusion pore expansion and granule cargo release. Syt-7 pores usually
      fail to expand (or reseal), slowing the dispersal of lumenal cargo proteins and
      granule membrane proteins. On the other hand, Syt-1 diffuses from fusion sites
      and promotes the release of lumenal cargo proteins. These findings suggest one
      way in which chromaffin cells may regulate cargo release is via differential
      activation of synaptotagmin isoforms. 

PMID- 24943844
TI  - SUMOylation of GPS2 protein regulates its transcription-suppressing function.
AB  - G-protein pathway suppressor 2 (GPS2) is a human suppressor of G protein
      activated mitogen-activated protein kinase signaling. It is involved in many
      physiological processes, including DNA repair, cell proliferation, apoptosis, and
      brain development. In this study, we show that GPS2 can be modified by the small
      ubiquitin-like modifier (SUMO) SUMO-1 but not SUMO-2 or -3. Two SUMOylation sites
      (K45 and K71) are identified in the N-terminal coiled-coil domain of GPS2.
      Substitution of K45 with arginine reduces SUMOylation, whereas substitution of
      K71 or both K45 and K71 with arginine abolishes SUMOylation, with more of the
      double mutant GPS2 appearing in the cytosol than in the nucleus compared with
      wild type and the two-single-mutant GPS2. SUMOylation stabilizes GPS2 protein by
      promoting its interaction with TBL1 and reducing its ubiquitination. SUMOylation
      also enhances the ability of GPS2 to suppress transcription and promotes its
      ability to inhibit estrogen receptor alpha-mediated transcription by increasing
      its association with SMRT, as demonstrated in MCF-7 and T47D cells. Moreover,
      SUMOylation of GPS2 also represses the proliferation of MCF-7 and T47D cells.
      These findings suggest that posttranslational modification of GPS2 by SUMOylation
      may serve as a key factor that regulates the function of GPS2 in vivo. 

PMID- 24943845
TI  - CEBPA exerts a specific and biologically important proapoptotic role in
      pancreatic beta cells through its downstream network targets.
AB  - Transcription factor CEBPA has been widely studied for its involvement in
      hematopoietic cell differentiation and causal role in hematological malignancies.
      We demonstrate here that it also performs a causal role in cytokine-induced
      apoptosis of pancreas beta cells. Treatment of two mouse pancreatic alpha and
      beta cell lines (alphaTC1-6 and betaTC1) with proinflammatory cytokines IL-1beta,
      IFN-gamma, and TNF-alpha at doses that specifically induce apoptosis of betaTC1
      significantly increased the amount of mRNA and protein encoded by Cebpa and its
      proapoptotic targets, Arl6ip5 and Tnfrsf10b, in betaTC1 but not in alphaTC1-6.
      Cebpa knockdown in betaTC1 significantly decreased cytokine-induced apoptosis,
      together with the amount of Arl6ip5 and Tnfrsf10b. Analysis of the network
      comprising CEBPA, its targets, their first interactants, and proteins encoded by
      genes known to regulate cytokine-induced apoptosis in pancreatic beta cells
      (genes from the apoptotic machinery and from MAPK and NFkB pathways) revealed
      that CEBPA, ARL6IP5, TNFRSF10B, TRAF2, and UBC are the top five central nodes. In
      silico analysis further suggests TRAF2 as trait d'union node between CEBPA and
      the NFkB pathway. Our results strongly suggest that Cebpa is a key regulator
      within the apoptotic network activated in pancreatic beta cells during insulitis,
      and Arl6ip5, Tnfrsf10b, Traf2, and Ubc are key executioners of this program. 

PMID- 24943846
TI  - Control of antioxidative response by the tumor suppressor protein PML through
      regulating Nrf2 activity.
AB  - Oxidative stress is a consequence of an imbalance between reactive oxygen species
      (ROS) production and the ability of the cytoprotective system to detoxify the
      reactive intermediates. The tumor suppressor promyelocytic leukemia protein (PML)
      functions as a stress sensor. Loss of PML results in impaired mitochondrial
      complex II activity, increased ROS, and subsequent activation of nuclear factor
      erythroid 2-related factor 2 (Nrf2) antioxidative pathway. We also demonstrate
      that sulforaphane (SFN), an antioxidant, regulates Nrf2 activity by controlling
      abundance and subcellular distribution of PML and that PML is essential for SFN
      mediated ROS increase, Nrf2 activation, antiproliferation, antimigration, and
      antiangiogenesis. Taking the results together, we have uncovered a novel
      antioxidative mechanism by which PML regulates cellular oxidant homeostasis by
      controlling complex II integrity and Nrf2 activity and identified PML as an
      indispensable mediator of SFN activity. 

PMID- 24943847
TI  - Mechanochemical regulation of oscillatory follicle cell dynamics in the
      developing Drosophila egg chamber.
AB  - During tissue elongation from stage 9 to stage 10 in Drosophila oogenesis, the
      egg chamber increases in length by ~1.7-fold while increasing in volume by
      eightfold. During these stages, spontaneous oscillations in the contraction of
      cell basal surfaces develop in a subset of follicle cells. This patterned
      activity is required for elongation of the egg chamber; however, the mechanisms
      generating the spatiotemporal pattern have been unclear. Here we use a
      combination of quantitative modeling and experimental perturbation to show that
      mechanochemical interactions are sufficient to generate oscillations of myosin
      contractile activity in the observed spatiotemporal pattern. We propose that
      follicle cells in the epithelial layer contract against pressure in the expanding
      egg chamber. As tension in the epithelial layer increases, Rho kinase signaling
      activates myosin assembly and contraction. The activation process is cooperative,
      leading to a limit cycle in the myosin dynamics. Our model produces asynchronous
      oscillations in follicle cell area and myosin content, consistent with
      experimental observations. In addition, we test the prediction that removal of
      the basal lamina will increase the average oscillation period. The model
      demonstrates that in principle, mechanochemical interactions are sufficient to
      drive patterning and morphogenesis, independent of patterned gene expression.

PMID- 24943849
TI  - Looking for sensitization profiles in different populations by recombinant
      allergens.

PMID- 24943850
TI  - Rectal swab for detection of norovirus by real-time PCR: similar sensitivity
      compared to faecal specimens.
AB  - Rapid diagnosis and immediate infection control precautions are cornerstones in
      the prevention of norovirus outbreaks. However, faecal sampling for norovirus PCR
      -the standard of care--is time consuming. From 2009 to 2011, parallel faecal and
      rectal swab samples were consecutively obtained from patients with acute
      gastroenteritis presenting at our emergency department. In total, 109 complete
      sample pairs of 108 patients were analysed by specific norovirus real-time PCR.
      The sensitivity of real-time PCR was 97.3% (36/37) for both sampling methods. A
      rectal swab is a reasonable option for detection of norovirus by real-time PCR,
      if a stool specimen is not readily available.

PMID- 24943852
TI  - Evolution of chemical bonding and electron density rearrangements during D(3h) ->
      D(3d) reaction in monolayered TiS2: a QTAIM and ELF study.
AB  - Monolayered titanium disulfide TiS2, a prospective nanoelectronic material, was
      previously shown to be subject to an exothermic solid-state D3h -D3d reaction
      that proceeds via a newly discovered transition state. Here, we study the
      reaction in detail using topological methods of quantum chemistry (quantum theory
      of atoms in molecules and electron localization function analysis) and show how
      electron density and chemical bonding between the atoms change in the course of
      the reaction. The reaction is shown to undergo a series of topological
      catastrophes, associated with elementary chemical events such as break and
      formation of bonds (including the unexpected formation of S-S bonding between
      sulfur layers), and rearrangement of electron density of outer valence and core
      shells.

PMID- 24943851
TI  - A randomized clinical trial of an integrated behavioral self-management
      intervention Simultaneously Targeting Obesity and Pain: the STOP trial.
AB  - BACKGROUND: Obesity often occurs co-morbid with chronic, non-cancer pain. While
      behavioral treatments have proved effective for pain management and weight loss
      independently, integrated interventions are lacking. The study Simultaneously
      Targeting Obesity and Pain (STOP) is a prospective, pragmatic, randomized
      controlled trial that aims to determine whether overweight/obese individuals with
      chronic pain who are randomized to receive an integrated treatment Simultaneously
      Targeting Obesity and Pain (STOP) will show more weight loss and greater
      reduction in pain intensity over a 6-month period and greater maintenance at 12
      months than those who receive standard care behavioral weight loss or standard
      care behavioral pain management. We hypothesize that individuals randomized to
      receive the STOP treatment will demonstrate improved weight loss, pain reduction,
      and maintenance compared to standard care treatment approaches. METHODS/DESIGN:
      Adults aged >= 18 with a body mass index >= 25 and who report persistent pain
      (>=4 out of 0-10 for > 6 months) will be recruited for treatment at the Health
      Behavior Research Lab at the University of the Sciences. After baseline
      assessments and goal setting, participants will be randomized to receive one of
      three treatments. Participants will receive eleven treatment sessions delivered
      during 1 hour, weekly individual meetings with a clinic therapist. Follow-up will
      occur at 3, 6 and 12-month time points; assessments will include measures of
      weight and pain intensity (primary outcomes). A mixed-method approach to
      evaluating study outcomes will include individual interviews with participants
      about their treatment experience. These interviews will be led by a research
      staffer who was not involved in study intervention or assessment using a semi
      structured discussion guide. DISCUSSION: This study fills an important gap in
      intervention research, evaluating best-practices for behavioral management of a
      highly prevalent co-morbidity that has sub-optimal outcomes with currently
      implemented approaches. STOP's pragmatic focus builds upon treatments already in
      use in clinical practice. Should STOP be found efficacious in achieving the dual
      outcomes of pain management and weight loss, such an approach could be integrated
      into practice with minimal additional cost or training. TRIAL REGISTRATION:
      Clinical Trials.gov NCT02100995 Date of Registration: March 2014.

PMID- 24943848
TI  - Integration of biological data by kernels on graph nodes allows prediction of new
      genes involved in mitotic chromosome condensation.
AB  - The advent of genome-wide RNA interference (RNAi)-based screens puts us in the
      position to identify genes for all functions human cells carry out. However, for
      many functions, assay complexity and cost make genome-scale knockdown experiments
      impossible. Methods to predict genes required for cell functions are therefore
      needed to focus RNAi screens from the whole genome on the most likely candidates.
      Although different bioinformatics tools for gene function prediction exist, they
      lack experimental validation and are therefore rarely used by experimentalists.
      To address this, we developed an effective computational gene selection strategy
      that represents public data about genes as graphs and then analyzes these graphs
      using kernels on graph nodes to predict functional relationships. To demonstrate
      its performance, we predicted human genes required for a poorly understood
      cellular function-mitotic chromosome condensation-and experimentally validated
      the top 100 candidates with a focused RNAi screen by automated microscopy.
      Quantitative analysis of the images demonstrated that the candidates were indeed
      strongly enriched in condensation genes, including the discovery of several new
      factors. By combining bioinformatics prediction with experimental validation, our
      study shows that kernels on graph nodes are powerful tools to integrate public
      biological data and predict genes involved in cellular functions of interest. 

PMID- 24943853
TI  - [Case management based multidisciplinary care protocol in the palliative care of
      cancer patients].
AB  - Today, multifaceted approach is needed for the palliative care of advanced stage
      cancer patients. The main objective for these patients, elimination of pain and
      other symptoms, psychosocial and spiritual needs are met and to increase the
      quality of life. We are also faced with the challenge of meeting the physical and
      psychosocial needs of family members. The purpose of a holistic approach to
      patient and family who provide effective and quality care, care coordination and
      case management of a multidisciplinary team approach is based on cooperation.
      Care protocols specified patient care activities to be carried by the related
      disciplines to achieve results on a timeline that shows a certain, a
      multidisciplinary clinical management tool. A lot of care guidelines and
      protocols developed by a team of experts to contribute to the palliative care
      activities, and this is thought to be a guiding team members, working with
      patients. 

PMID- 24943854
TI  - [Pain management of elderly in nursing homes].
AB  - OBJECTIVES: The aim of this study was to determine pain management status of the
      elderly in nursing homes. METHODS: The descriptive study sample included 82
      elderly who presented to two nursing homes in Izmir between February-July 2012.
      In this study, Elderly Identification Form, Mini-Mental Scale, McGill Pain Scale
      (MAS) and Pain Management Inventory were used as the data collection tool.
      RESULTS: It was determined that the highest rates of complaints the elderly
      individuals had were knee pain (64.6%) and headache (58.5%) in this study. Of the
      elderly people participating in the study, 96.3% took pain relievers for pain
      management and according to their statements, of the pain management methods they
      used, resting and directing attention to something else (X=5.76+/-0.87) and
      taking prescribed pain relievers (X=5.69+/-0.87) were very beneficial.
      CONCLUSION: In elderly individuals, it is important to use pharmacological and
      non-pharmacological methods for pain management. Therefore, it is recommended to
      determine the most frequently used methods for pain management by the elderly and
      to integrate them into the care plan.

PMID- 24943855
TI  - [Comparison the effects of prilocaine and the addition of dexketoprofen and
      dexamethasone to prilocaine for intravenous regional anesthesia].
AB  - OBJECTIVES: The aim of this study was to compare the anesthetic and analgesic
      effects of prilocaine alone, prilocaine added dexketoprofen and dexamethasone
      during intravenous regional anesthesia (IVRA). METHODS: Forty five patients
      undergoing forearm or hand surgery were randomly assigned to one of three groups
      to receive (Group P) 3 mg/kg 0.5% prilocaine; (Group PDK) 3 mg/kg 0.5% prilocaine
      plus 50 mg dexketoprofen; (Group PDM) 3 mg/kg 0.5% prilocaine plus 8 mg
      dexamethasone in total 40 ml volume for IVRA. The onset and duration of sensory
      and motor blocks, hemodynamic datas, duration of analgesia and tourniquet, time
      to first analgesic requirement, visual analog scale (VAS), total analgesic
      consumption in 24 hours and patient satisfaction score were assessed and
      recorded. RESULTS: Time to onset of sensory block was found to be longer in Group
      P (p<0.05), though no significance was found according to sensory block recovery
      times amoung groups. Time to onset of motor block was found to be longer and
      recovery time of motor block was found to be shorter in Group P (p<0.05). Time to
      first analgesic requirement was found to be longer in Group PDK,and was found to
      be high in Group PDM than Group PDK(p<0.05). The VAS scores was found to be high
      and patient satisfaction scale was found to be low in Group P (p<0.05).
      CONCLUSION: The addition of dexketoprofen and dexamethasone to prilocaine during
      IVRA improves the quality of both anesthesia and analgesia moreover dexketoprofen
      provides beter postoperative analgesia during the first 24 hour after surgery.

PMID- 24943856
TI  - [Preemptive analgesic efficacy of gabapentin and nimesulide in the functional
      endoscopic sinus surgery].
AB  - OBJECTIVES: Preemptive analgesia is an important factor in controlling the
      postoperative pain and avoiding the stress response caused by the surgery. We aim
      to compare impact of gabapentin and nimesulide on postoperative analgesic
      consumption on the visual analog scale (VAS) as well as any potential side
      effects, to those of the placebo group. METHODS: Ninety patients aged 18-70 under
      ASA I-II risk, who were to undergo Functional Endoscopic Sinus Surgery (FESS),
      were included in the study. Patients were randomized into three groups. One hour
      before the surgery, oral placebo capsules were administered to Group I patients,
      Gabapentin 1200 mg to Group II patients and Nimesulide 100 mg to Group III
      patients. Perioperative hemodynamic parameters were measured for all patients.
      During the first 24 hours of the postoperative period, side effects such as
      nausea, vomiting, hypotension, hypertension, bradycardia, tachycardia were noted,
      and the time from end of the surgery to the first diclofenac need was recorded in
      addition to VAS scores. RESULTS: In all of the follow-ups for 24 hours of the
      postoperative period, time from end of the surgery until the first diclofenac
      requirement; Group 2 > Group 3 > Group 1. Total diclofenac consumption of group 2
      was found to be significantly lower than Group 1 and Group 3 on a statistical
      basis. Postoperative VAS score in Group 2 was lower than Group 1 and Group 3.
      CONCLUSION: To conclude, we believe that gabapentin or nimesulide may be safely
      used preemptively for the purposes of postoperative analgesia after FESS
      procedures.

PMID- 24943857
TI  - [Effect of intravenous dexketoprofen use on postoperative analgesic consumption
      in patients with lumbar disc surgery].
AB  - OBJECTIVES: The objective of this study was to evaluate the postoperative
      analgesic effect of a preemptive, single-dose intravenous dexketoprofen
      administration in patients undergoing lumbar microdiscectomy. METHODS: A total of
      50 ASA I-II patients candidate to laminectomy were included in this study. They
      were divided in two groups. Patients in Group A were given 50 mg (2 mL)
      dexketoprofen and those in Group K 2 mL normal saline intravenously by a blinded
      anesthesia physician, 10 minutes before the start of intervention. All cases
      underwent general anesthesia. All patients received postoperative patient
      controlled analgesia with tramadol. The VAS scores 1, 4, 8, 16 and 24 hours
      following the operation, sedation and patient satisfaction scores and tramadol
      consumption were evaluated. RESULTS: VAS scores recorded during the first 8
      postoperative hours and total tramadol amounts were lower, and the patient
      satisfaction scores higher, in patients given dexketoprofen than control group.
      Sedation scores and side effects were similar in both groups. CONCLUSION: Single
      dose preemptive intravenous dexketoprofen provides effective analgesia especially
      in the first 8 postoperative hours, reducing tramadol use.

PMID- 24943858
TI  - [The coexistence of Tolosa-Hunt syndrome and diabetic cranial mononeuropathy: a
      case report and a review of literature].
AB  - Tolosa-Hunt syndrome (THS) is described as painful ophtalmoplegia caused by
      nonspesific inflammation of cavernous sinus or superior orbital fissure, which is
      response to steroid theraphy. Cranial neuropathies in diabetic patients are
      extremely rare and occur in older patients with poorly controlled diabetes. A 56
      year-old diabetic female patient who developed simultaneous right VI., left III.,
      IV., VI., VII. and maxiller branch of trigeminal nerve palsies with acute
      periorbital pain applied to our outpatient clinic. Although the coexistence of
      THS and diabetic cranial neuropathy is an uncommon condition, this should be
      considered as a possible diagnosis on patients who are admitted with painful
      ophtalmoplegia and simultaneous multipl cranial neuropathies. We approved to
      present our diabetic patient with cranial magnetic imaging because of this
      interesting unity and fasial nerve palsy accompanying to THS. 

PMID- 24943859
TI  - Pain management with intrathecal clonidine in a colon cancer patient with opioid
      hyperalgesia: case presentation.
AB  - Hyperalgesia is normally an increase in the response to a painful stimulant.
      Opioid-induced hyperalgesia (OIH) is a situation frequently encountered in
      algology clinics. Its treatment is complicated and problematic and often requires
      alternative methods. A 40-year-old male patient 45 kg weighing had been diagnosed
      with stage IV colon cancer 2.5 years ago. He had used non-steroid
      antiinflammatory drugs, opioid analgesics and steroid preparations casually for
      his increased pain without any monitoring for one year. He was admitted five
      times for pain control. In the last visit, he complained of severe abdominal,
      pubic and rectal pain (visual analogue scale [VAS] 8), which was unresponsive to
      epidural analgesic, and later presented to the algology clinic; he was sleep
      deprived, restless and in a panic state. Intrathecal morphine (1 mg) was applied
      considering his opioid tolerance. Because of increased pain (VAS 8-9) one hour
      after surgery for abscess in the liver and peritonea, the patient was given
      intravenous dexketoprofen trometamol and diazem considering his OIH. Then, bolus
      dexmedetomidine (1 ug/kg) followed by dexmedetomidine infusion (0.2 ug/kg/h) was
      started. Three days later, diagnostic intrathecal clonidine (30 ug) was applied,
      and the patient's complaints regressed. With the patient reporting relaxed pain
      (VAS 1-2) after 30 minutes, an intrathecal port was placed. Both cancer pain and
      OIH were controlled with clonidine 90 ug/day. He was more relaxed, and his pain
      was tolerable until his death. Intrathecal clonidine administration may be an
      effective method for the treatment of OIH. 

PMID- 24943860
TI  - [Complication belong to stellate ganglion blockade after cervical trauma].
AB  - Stellate ganglion block (SGB) is one of the most often used sympathetic blockade
      procedure. Despite performed by experienced physicians some complications may
      occur. The right brachial plexus injury was diagnosed in the patient who admitted
      to orthopedia clinic, with weakness in the right arm, and pain after motor
      vehicle accident. There was no response to medical treatment of fortyfour-years
      old female patient and there was loosing of sensation from dis the right elbow
      joint to fingers on the radial and median nerve tracing. In the
      electromyelography; C5-T1 root avulsion, and MRI; Patient was evaluated as CPRS I
      (Complex regional pain syndrome) phase 1. In spite of medical treatment, SGB was
      performed. Respiratory arrest occurred 4-5 minutes after injection. Patient was
      breated with mechanical ventilator during 2 hours, and discharged 24 hours later
      with normal vital functions. One year later, the patient admitted the algology
      polyclinic with strong pain in the same area. Stellate ganglion Radyofreguency
      (RF) was planned. The first RF cannula was placed under fluoroscopy.
      Cerebrospinal fluid was seen in the second canula, and canula was withdrawn.
      Third cannula was placed in another region, and conventional RF was performed
      through two canuls. For anatomical structure defect, we planned cervical MR
      myelography. In the cervical MR myelography, traumatic pseudomeningocele was
      observed at the level of C6-T1 on the brachial plexus. Intraspinal block was
      thought to develop during blockade of stellate ganglion due to this. 

PMID- 24943861
TI  - Restorative treatment thresholds: factors influencing the treatment thresholds
      and modalities of general dentists in Kuwait.
AB  - OBJECTIVES: This study investigated the thresholds at which general dentists in
      Kuwait would restore approximal and occlusal carious lesions and examined the
      demographic characteristics of the dentists in relation to their decision making.
      SUBJECTS AND METHODS: The study population consisted of a random sample of 185
      general dentists practicing in the Ministry of Health of Kuwait. A survey
      questionnaire was administered. The questionnaire presented different stages and
      locations of carious lesions; the participants were asked to identify the stage
      at which a restoration is required under different conditions, the preparation
      technique, and their choice of restorative material. RESULTS: For approximal
      carious lesions, 74 (40%) of the participants reported that they would
      restoratively intervene when the carious lesion reached the outer third of the
      dentin. A total of 91 (49.2%) reported the use of traditional class II
      restorations. For occlusal carious lesions, 128 (69.2%) said they would intervene
      when lesions reached the middle third of the dentin. 146 (78.9%) said they would
      remove the carious tissue only in their preparation. For both approximal and
      occlusal lesions, the participants preferred resin composite as the material for
      restoration. CONCLUSIONS: The respondents tended to delay restorative
      intervention until dentinal penetration of the caries. Resin restorative
      materials were used in conservatively prepared cavities. Participants chose a
      conservative approach for occlusal lesions but still believed in a traditional
      approach when it concerned approximal lesions. Experience, university dental
      education, and participation in continuous education courses were most
      significantly related to restorative treatment.

PMID- 24943862
TI  - The stability of xylem water under tension: a long, slow spin proves
      illuminating.

PMID- 24943864
TI  - Shoreline development and degradation of coastal fish reproduction habitats.
AB  - Coastal development has severely affected habitats and biodiversity during the
      last century, but quantitative estimates of the impacts are usually lacking. We
      utilize predictive habitat modeling and mapping of human pressures to estimate
      the cumulative long-term effects of coastal development in relation to fish
      habitats. Based on aerial photographs since the 1960s, shoreline development
      rates were estimated in the Stockholm archipelago in the Baltic Sea. By combining
      shoreline development rates with spatial predictions of fish reproduction
      habitats, we estimated annual habitat degradation rates for three of the most
      common coastal fish species, northern pike (Esox lucius), Eurasian perch (Perca
      fluviatilis) and roach (Rutilus rutilus). The results showed that shoreline
      constructions were concentrated to the reproduction habitats of these species.
      The estimated degradation rates, where a degraded habitat was defined as having
      >=3 constructions per 100 m shoreline, were on average 0.5 % of available
      habitats per year and about 1 % in areas close to larger population centers.
      Approximately 40 % of available habitats were already degraded in 2005. These
      results provide an example of how many small construction projects over time may
      have a vast impact on coastal fish populations.

PMID- 24943863
TI  - Lower regional and temporal ultraviolet exposure is associated with increased
      rates and severity of inflammatory bowel disease hospitalisation.
AB  - BACKGROUND: In the northern hemisphere, the incidence of inflammatory bowel
      diseases (IBD) has a north-south gradient, suggesting a link between ultraviolet
      (UV) exposure or vitamin D status and the pathogenesis of IBD. AIM: To test the
      association of UV exposure with the rates and severity of IBD hospitalisation.
      METHODS: We conducted a retrospective nationwide analysis of 649 932 Crohn's
      disease (CD), 384 267 ulcerative colitis (UC), and 288 894 297 non-IBD
      hospitalisations in the US between 1998 and 2010. Mean UV exposure was assigned
      to each hospitalisation using surface measures from the National Oceanic and
      Atmospheric Administration. Relative rates across UV exposures were estimated for
      IBD hospitalisations, prolonged hospitalisations, bowel surgeries and deaths.
      RESULTS: Among IBD patients, lower UV exposures had increased hospitalisation
      rates for CD (217.8 vs. 182.5 per 100 000 overall hospitalisations with low and
      very high UV, respectively; P trend <0.001) and UC (123.2 vs. 113.8 per 100 000;
      P trend = 0.033). Low UV groups had greater relative rates of prolonged
      hospitalisations [CD: 1.13, 95% confidence interval (CI) 1.07-1.19; UC: 1.21, 95%
      CI 1.13-1.30], bowel surgeries (CD: 1.24, 95% CI 1.16-1.32; UC: 1.21, 95% CI 1.09
      1.33), and CD deaths (CD: 1.76, 95% CI 1.14-2.71; UC: 1.24, 95% CI 0.92-1.67).
      Among non-IBD patients, low UV was associated with prolonged hospitalisations
      (1.09; 95% CI 1.07-1.11) and deaths (1.13; 95% CI 1.09-1.17), but not bowel
      surgeries (1.01; 95% CI 0.99-1.03). CONCLUSIONS: Lower ultraviolet exposure is
      associated with greater rates of hospitalisation, prolonged hospitalisation and
      the need for bowel surgery in IBD. This trend for bowel surgery was not seen with
      non-IBD encounters.

PMID- 24943865
TI  - BAC chromosomal microarray for prenatal detection of chromosome anomalies in
      fetal ultrasound anomalies: an economic evaluation.
AB  - INTRODUCTION: To determine the cost-effectiveness of prenatal chromosomal
      microarray (CMA) when performed for structural anomalies on fetal ultrasound scan
      over conventional techniques. METHOD: A decision tree was populated using data
      from a prospective cohort of women undergoing testing when a fetal ultrasound
      scan showed a structural abnormality. Nine strategies of testing were modeled
      including combinations of the tests: QFPCR, G-band karyotyping, CMA and FISH for
      DiGeorge (22q) microdeletion. RESULTS: When CMA costs GBP 405 and using a 1-Mb
      BAC array it would cost GBP 24,600 for every additional case detected by CMA over
      a combination of QFPCR, followed by G-band karyotype, followed lastly by FISH
      (for DiGeorge syndrome). If CMA is performed instead of conventional karyotyping
      alone it costs GBP 33,000 for every additional case detected. However, if the
      cost of CMA is reduced to GBP 360 than when CMA is performed instead of
      conventional karyotyping alone it would cost GBP 9,768 for every additional case
      detected. DISCUSSION: The use of a prenatal BAC CMA is not currently cost
      effective when compared to other testing strategies. However, as CMA costs
      decrease and resolution (and detection rates) increase it is likely to become the
      cost-effective option of the future.

PMID- 24943867
TI  - Brief Report: identification of MTMR3 as a novel susceptibility gene for lupus
      nephritis in northern Han Chinese by shared-gene analysis with IgA nephropathy.
AB  - OBJECTIVE: Several novel susceptibility genes for systemic lupus erythematosus
      (SLE) and IgA nephropathy have been identified in recent genome-wide association
      studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases
      of the kidney, they may share common disease mechanisms that overlap with genetic
      susceptibility. To test this hypothesis, we sought to identify genetic variants
      associated with IgA nephropathy in lupus nephritis. METHODS: In the first stage,
      500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500
      healthy controls were enrolled. Fifteen single-nucleotide polymorphisms (SNPs)
      that had the topmost association signals with IgA nephropathy were selected for
      further testing in patients with lupus nephritis. Three independent cohorts from
      Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed
      the functional significance of identified noncoding variants on regulatory motifs
      and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs)
      were calculated. RESULTS: In addition to associations with HLA gene
      polymorphisms, genetic variants of MTMR3 in 22q12 showed associations with lupus
      nephritis (for rs9983A, OR 1.61 [95% CI 1.19-2.19], P = 2.07 * 10(-3) ) compared
      to healthy controls in the first stage. Associations were replicated and
      reinforced among northern Han Chinese (for lupus nephritis patients versus SLE
      patients without nephritis, P = 0.01) but not southern Han Chinese, although
      significant genetic heterogeneity was observed. Conservative and regulatory
      features of rs9983 were predicted in in silico analyses. In expression analysis,
      we observed lower MTMR3 transcription levels in samples of blood with rs9983A and
      in renal biopsy samples from lupus nephritis and IgA nephropathy patients.
      CONCLUSION: Our results suggest that the MTMR3 gene is shared between IgA
      nephropathy and lupus nephritis in the northern Chinese population, further
      highlighting the role of autophagy in SLE. However, widespread replication of
      these experiments, fine mapping, and functional assays are required to establish
      this connection.

PMID- 24943869
TI  - Clinicopathological and immunohistochemical study of 30 cases of post-radiation
      atypical vascular lesion of the breast.
AB  - Atypical vascular lesions (AVL) that occur in the field of prior radiation
      therapy for breast carcinoma are placed within the differential diagnosis with
      low grade angiosarcoma and other benign vascular lesions. Although considered a
      benign entity, the exact biological behavior of AVLs is not fully established
      because of the small number of cases reported in the literature. We aim to
      further characterize these lesions clinically and histopathologically, and to
      study their behavior. We report a series of 30 patients with AVL of the breast
      occurring after radiation exposure, diagnosed and treated at the European
      Institute of Oncology, Italy. Immunohistochemical study was performed in all
      cases, using CD31, D2-40, CD105, and Ki-67 antibodies. Twenty-seven patients were
      treated with standard doses of conventional adjuvant radiation therapy for the
      prior breast carcinoma. Three patients were treated with intraoperative
      radiotherapy with electrons. The post-radiation latency interval from breast
      carcinoma to AVL was 48.5 months (ranged from 1 to 146 months). Most of the
      lesions were classified as lymphatic type (78.6 %) based on D2-40 positivity. No
      extension into subcutaneous tissue or significant atypia was noted in all cases.
      Despite the fact that the AVL of our series have shown benign behavior in 93.3 %,
      one patient developed local recurrence of AVL, and two cases progressed to
      angiosarcoma at the previous AVL site. Further studies should be conducted to
      better understand the clinical behavior and to propose additional histopathologic
      diagnostic criteria to distinguish AVL from low grade angiosarcoma and those AVL
      with increased risk for malignant progression. Concerning current treatments of
      AVL, we recommend complete excision with free surgical margins and close follow
      up.

PMID- 24943866
TI  - Antimicrobial resistance in urinary isolates from inpatients and outpatients at a
      tertiary care hospital in South-Kivu Province (Democratic Republic of Congo).
AB  - BACKGROUND: The rate of antimicrobial resistant isolates among pathogens causing
      urinary tract infections (UTIs) in Democratic Republic of Congo (DRC) is not
      known. The aim of the current study was to determine this rate at the Bukavu
      Provincial General Hospital (province of South-Kivu, DRC). FINDINGS: A total of
      643 isolates (both from inpatients and outpatients) collected from September 2012
      to August 2013 were identified using biochemical methods, and tested for
      antimicrobial susceptibility. The isolates were further screened for Extended
      Spectrum Beta-Lactamases (ESBL) production. Beta-lactamase AmpC phenotype was
      investigated in 20 antibiotic-resistant isolates.Escherichia coli (58.5%),
      Klebsiella spp. (21.9%) and Enterobacter spp. (16.2%) were the most frequent
      uropathogens encountered. Rare uropathogens included Citrobacter spp., Proteus
      spp., and Acinetobacter spp. Resistance was significantly more present in
      inpatients isolates (22.1% of isolates) when compared to outpatients isolates
      (8.4% of isolates), (p-value <0.001). Antibiotic-resistant isolates displayed
      resistance to common antimicrobial drugs used for UTIs treatment in South Kivu
      province, namely: ciprofloxacin, ampicillin and third generation cephalosporins.
      ESBL-phenotype was present in 92.9% of antibiotic-resistant isolates. Only
      amikacin, nitrofurantoin and imipenem displayed satisfactory activity against
      antibiotic resistant isolates. CONCLUSIONS: This study confirms the presence of
      antibiotic-resistant uropathogens (mainly ESBL-producers isolates) at the Bukavu
      General Hospital. This study should serve as a wake-up call and help to raise
      awareness about the threat to public health of antibiotic resistance in this DRC
      province.

PMID- 24943870
TI  - Risk assessment of butyltins based on a fugacity-based food web bioaccumulation
      model in the Jincheng Bay mariculture area: I. Model development.
AB  - A fugacity-based model was developed to simulate the bioaccumulation of butyltins
      in the food web of the Jincheng Bay mariculture area. The predicted biological
      tissue residues of tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT)
      were 0.04-17.09, 0.14-53.54, and 0.27-108.77 ng-Sn g(-1), respectively, and the
      predicted values in six mollusca agreed well with the measured ones. The lipid
      normalized concentrations did not significantly increase across trophic levels,
      indicating no biomagnification across aquatic food webs. These results were
      highly consistent with those observed both in the laboratory and field, which had
      been reported in numerous references. The explanation, from calculating their
      flux equilibrium in the food web, was that butyltins were primarily taken in via
      respiration from the water column by marine organisms. The sensitivities of the
      model parameters were analyzed, revealing that the hydrophobicity of butyltins
      played the dominant role in their bioaccumulation phenomena. The verified model
      predictions of the biotic tissue concentrations of the butyltins could be readily
      applied to perform internal ecological risk and human health risk assessments in
      this area.

PMID- 24943871
TI  - Adenocarcinoma on colon interposition for corrosive esophageal injury: case
      report and review of literature.

PMID- 24943872
TI  - Presence of human polyomavirus 6 in mutation-specific BRAF inhibitor-induced
      epithelial proliferations.
AB  - IMPORTANCE: A frequent adverse effect of mutation-specific BRAF inhibitor therapy
      is the induction of epithelial proliferations including cutaneous squamous cell
      carcinomas. To date, the only factor identified contributing to their development
      is the activation of the mitogen-activated signal transduction cascade by
      mutations in the RAS genes. However, these mutations explain only 60% of the
      tumors; hence, it is important to identify what is causing the remaining tumors.
      OBJECTIVE: To test for the presence of human papillomaviruses (HPVs) and the
      recently identified human polyomaviruses (HPyVs), Merkel cell polyomavirus
      (MCPyV), and trichodysplasia spinulosa-associated polyomavirus (TSPyV), as well
      as HPyV-6, HPyV-7, HPyV-9, and HPyV-10, in epithelial proliferations occurring
      after BRAF inhibitor therapy to determine whether these oncogenic viruses may
      contribute to BRAF inhibitor-induced skin tumors. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective study at a university hospital in Austria of
      epithelial proliferations that developed in patients with melanoma after
      initiation of treatment with the BRAF inhibitor vemurafenib. Samples were
      analyzed for (1) presence of the most frequently observed RAS mutations by
      SNaPshot technology, (2) detection of the viruses by real-time polymerase chain
      reaction, and (3) presence of capsid proteins of the most abundantly detected
      virus by immunohistochemical analysis. MAIN OUTCOMES AND MEASURES: RAS mutational
      status, as well as HPV and HPyV presence, in BRAF inhibitor-induced epithelial
      proliferations. RESULTS: Eighteen biopsy samples from 6 patients were retrieved
      from our hospital's archive. We identified RAS mutations in 10 (62%) of the 16
      samples with clear results. DNA of HPyV-9, HPyV-10, and TSPyV were virtually
      absent in the samples. MCPyV DNA was present in 13 of 18 samples, and HPV, HPyV
      6, and HPyV-7 DNA were present in all samples. In general, the amount of DNA
      encoding the latter viruses was rather low, with the exception of HPyV-6 in
      several samples of 1 individual patient. Notably, the relevance of the presence
      of HPyV-6 in the epithelial proliferation was underlined by immunohistochemical
      detection of the core protein VP1 of HPyV-6. CONCLUSIONS AND RELEVANCE: The
      presence of both high HPyV-6 DNA load and VP1 protein suggests that
      polyomaviruses may contribute to the epithelial proliferations observed in
      patients receiving BRAF inhibitor therapy, albeit the relative impact as compared
      with that of RAS mutations appears circumstantial.

PMID- 24943874
TI  - Prompting professional prerogatives: new insights to reopen an old debate about
      nursing.
AB  - A profession is defined by neither a set of structural qualities nor a
      description idiosyncratic to a single culture. Rather, a profession detects
      problems in an area of work, intellectualizes that work, and offers solutions,
      developing a logic of competition with coexisting occupations. The best that
      structural explanations can offer to nursing is rigid, unmovable definitions such
      as "a semi-profession," whereas the ecological theory of the professions regards
      the continuous interplay among occupations cohabiting in an interacting system as
      the fundamental process of gaining or losing professional status. In this
      theoretically driven article we draw upon the notion of "social ecology of
      nursing" as a vector of development, arguing that nursing's professional status
      lies in its ability to adapt to "landscape" transformations and to protect its
      jurisdiction from competitors, equating fully established professions. In
      discussing the application of this theory, we invite readers to reopen a debate
      about the professional nature of nursing, considering cross-national versions of
      nursing for more comprehensive definitions of the profession. 

PMID- 24943873
TI  - Self-efficacy and health-related quality of life in family carers of people with
      dementia: a systematic review.
AB  - OBJECTIVES: This review aims to explore the role of self-efficacy (SE) in the
      health-related quality of life (QoL) of family carers of people with dementia.
      METHODS: A systematic review of literature identified a range of qualitative and
      quantitative studies. Search terms related to caring, SE, and dementia. Narrative
      synthesis was adopted to synthesise the findings. RESULTS: Twenty-two studies met
      the full inclusion criteria, these included 17 quantitative, four qualitative,
      and one mixed-method study. A model describing the role of task/domain-specific
      SE beliefs in family carer health-related QoL was constructed. This model was
      informed by review findings and discussed in the context of existing conceptual
      models of carer adaptation and empirical research. Review findings offer support
      for the application of the SE theory to caring and for the two-factor view of
      carer appraisals and well-being. Findings do not support the independence of the
      negative and positive pathways. The review was valuable in highlighting
      methodological challenges confronting this area of research, particularly the
      conceptualisation and measurement issues surrounding both SE and health-related
      QoL. CONCLUSIONS: The model might have theoretical implications in guiding future
      research and advancing theoretical models of caring. It might also have clinical
      implications in facilitating the development of carer support services aimed at
      improving SE. The review highlights the need for future research, particularly
      longitudinal research, and further exploration of domain/task-specific SE
      beliefs, the influence of carer characteristics, and other mediating/moderating
      variables.

PMID- 24943875
TI  - Cell death and tissue reorganization in Rhynchosciara americana (Sciaridae:
      Diptera) metamorphosis and their relation to molting hormone titers.
AB  - Programmed cell death (PCD) is a focal topic for understanding processes
      underlying metamorphosis in insects, especially so in holometabolous orders.
      During adult morphogenesis it allows for the elimination of larva-specific
      tissues and the reorganization of others for their functionalities in adult life.
      In Rhynchosciara, this PCD process could be classified as autophagic cell death,
      yet the expression of apoptosis-related genes and certain morphological aspects
      suggest that processes, autophagy and apoptosis may be involved. Aiming to reveal
      the morphological changes that salivary gland and fat body cells undergo during
      metamorphosis we conducted microscopy analyses to detect chromatin condensation
      and fragmentation, as well as alterations in the cytoplasm of late pupal tissues
      of Rhynchosciara americana. Transmission electron microscopy and confocal
      microscopy revealed cells in variable stages of death. By analyzing the
      morphological structure of the salivary gland we observed the presence of cells
      with autophagic vacuoles and apoptotic bodies and DNA fragmentation was confirmed
      with the TUNEL assay in salivary gland. The reorganization of fat body occurs
      with discrete detection of cell death by TUNEL assay. However, both salivary
      gland histolysis and fat body reorganization occur under control of the hormone
      ecdysone. 

PMID- 24943876
TI  - An ultrathin, smooth, and low-loss Al-doped Ag film and its application as a
      transparent electrode in organic photovoltaics.
AB  - An ultrathin, smooth, and low-loss Ag film without a wetting layer is achieved by
      co-depositing a small amount of Al into Ag. The film can be as thin as 6 nm, with
      a roughness below 1 nm and excellent mechanical flexibility. Organic
      photovoltaics that use these thin films as transparent electrode show superior
      efficiency to their indium tin oxide (ITO) counterparts because of improved
      photon management. 

PMID- 24943877
TI  - Systematic review of methods for individual patient data meta- analysis with
      binary outcomes.
AB  - BACKGROUND: Meta-analyses (MA) based on individual patient data (IPD) are
      regarded as the gold standard for meta-analyses and are becoming increasingly
      common, having several advantages over meta-analyses of summary statistics. These
      analyses are being undertaken in an increasing diversity of settings, often
      having a binary outcome. In a previous systematic review of articles published
      between 1999-2001, the statistical approach was seldom reported in sufficient
      detail, and the outcome was binary in 32% of the studies considered. Here, we
      explore statistical methods used for IPD-MA of binary outcomes only, a decade
      later. METHODS: We selected 56 articles, published in 2011 that presented results
      from an individual patient data meta-analysis. Of these, 26 considered a binary
      outcome. Here, we review 26 IPD-MA published during 2011 to consider: the goal of
      the study and reason for conducting an IPD-MA, whether they obtained all the data
      they sought, the approach used in their analysis, for instance, a two-stage or a
      one stage model, and the assumption of fixed or random effects. We also
      investigated how heterogeneity across studies was described and how studies
      investigated the effects of covariates. RESULTS: 19 of the 26 IPD-MA used a one
      stage approach. 9 IPD-MA used a one-stage random treatment-effect logistic
      regression model, allowing the treatment effect to vary across studies. Twelve
      IPD-MA presented some form of statistic to measure heterogeneity across studies,
      though these were usually calculated using two-stage approach. Subgroup analyses
      were undertaken in all IPD-MA that aimed to estimate a treatment effect or safety
      of a treatment,. Sixteen meta-analyses obtained 90% or more of the patients
      sought. CONCLUSION: Evidence from this systematic review shows that the use of
      binary outcomes in assessing the effects of health care problems has increased,
      with random effects logistic regression the most common method of analysis.
      Methods are still often not reported in enough detail. Results also show that
      heterogeneity of treatment effects is discussed in most applications.

PMID- 24943878
TI  - Impact of particle size and light exposure on the effects of TiO2 nanoparticles
      on Caenorhabditis elegans.
AB  - The increasing use of engineered nanoparticles in industrial and consumer
      products leads to a release of the anthropogenic contaminants to the aquatic
      environment. To obtain a better understanding of the environmental effects of
      these particles, the nematode Caenorhabditis elegans was used to investigate the
      organism-level effects and in vivo molecular responses. Toxicity of bulk-scale
      (~160 nm) and nanoscale (21 nm) titanium dioxide (TiO2 ) was tested under dark
      and light conditions, following ISO 10872. The expression of sod-3, a
      mitochondrial superoxide dismutase, was quantified as an indicator for oxidative
      stress induced by the photocatalytically active material. Particle sizes were
      estimated using dynamic light scattering and scanning electron microscopy.
      Although both materials agglomerated to a comparable secondary particle size of
      300 nm to 1500 nm and were ingested into the intestine, only nanoscale-TiO2
      significantly inhibited reproduction (lowest-observed-effect-concentration
      [LOEC]: 10 mg/L). Light exposure induced the production of reactive oxygen
      species (ROS) by nanoscale-TiO2 and increased toxicity of the nanomaterial from a
      median effect concentration of more than 100 mg/L to 53 mg/L. No evidence was
      found for inner cellular photocatalytic activity of nanoscale-TiO2 . Therefore,
      oxidative damage of the membranes of intestinal cells is suggested as a potential
      mode of action. Results highlight the importance of primary particle size and
      environmental parameters on the toxicity of TiO2 .

PMID- 24943879
TI  - Systemic immunosuppression by methylprednisolone and pregnancy rates in goats
      undergoing the transfer of cloned embryos.
AB  - The presence of the zona pellucida has been perceived as a requirement for the
      oviductal transfer of cloned embryos at early stages of development while
      protecting the embryo from an immune system response. We hypothesized that
      steroid hormone therapy could reduce a potential cellular immune response after
      the transfer of zona-free cloned embryos into the oviduct of recipient female
      goats. In Experiment 1, seven does were used to study the systemic
      immunosuppressant effect of the methylprednisolone administration (for 3 days) on
      blood cell counts. Whole blood was collected prior to treatment with
      methyprednisolone and then on Days 1, 2, 3, 4, 7, 14, 21 and 28 after the first
      dose of methylprednisolone for the analysis of haematological parameters.
      Methylprednisolone treatment significantly reduced circulating white blood cells
      and neutrophils in comparison with pre-treatment levels, demonstrating a systemic
      immunosuppressant effect. In Experiment 2, a group of 58 does were used as
      recipient females to study the effect of administration of methylprednisolone for
      3 days on the establishment of pregnancies after the transfer of zona-free cloned
      embryos into the oviducts. No effects on pregnancy rates on Day 30 were observed
      regarding the distinct treatment groups (control vs. methylprednisolone), the
      source of oocytes (in vivo- vs in vitro-matured) or the presence or absence of
      the zona pellucida in embryos. In summary, methylprednisolone was effective at
      inducing a systemic immunosuppressed state in goats, but the treatment prior to
      embryo transfer did not affect pregnancy rates. Moreover, pregnancy rates were
      similar between zona-free and zona-intact goat cloned embryos.

PMID- 24943881
TI  - Mutation-order divergence by sexual selection: diversification of sexual signals
      in similar environments as a first step in speciation.
AB  - The origin of species remains a central question, and recent research focuses on
      the role of ecological differences in promoting speciation. Ecological
      differences create opportunities for divergent selection (i.e. 'ecological'
      speciation), a Darwinian hypothesis that hardly requires justification. In
      contrast, 'mutation-order' speciation proposes that, instead of adapting to
      different environments, populations find different ways to adapt to similar
      environments, implying that speciation does not require ecological differences.
      This distinction is critical as it provides an alternative hypothesis to the
      prevailing view that ecological differences drive speciation. Speciation by
      sexual selection lies at the centre of debates about the importance of ecological
      differences in promoting speciation; here, we present verbal and mathematical
      models of mutation-order divergence by sexual selection. We develop three general
      cases and provide a two-locus population genetic model for each. Results indicate
      that alternative secondary sexual traits can fix in populations that initially
      experience similar natural and sexual selection and that divergent traits and
      preferences can remain stable in the face of low gene flow. This stable
      divergence can facilitate subsequent divergence that completes or reinforces
      speciation. We argue that a mutation-order process could explain widespread
      diversity in secondary sexual traits among closely related, allopatric species. 

PMID- 24943880
TI  - Clinical and molecular features of 38 children with chronic granulomatous disease
      in mainland china.
AB  - PURPOSE: Chronic granulomatous disease (CGD) is an inherited disorder, with
      phagocytes failing to produce antimicrobial superoxide due to deficient NADPH
      oxidase activity. Mutations in the gene encoding CYBB are responsible for the
      majority of the CGD cases. To date, there have been no reports on large samples
      of children with CGD in China. Therefore, in this study, we described the
      clinical and molecular features of 38 suspected CGD patients from 36 unrelated
      Chinese families. METHODS: Clinical diagnosis was performed using
      dihydrorhodamine assays detected by flow cytometry. Molecular analysis was used
      to identify underlying CGD-causative genes. RESULTS: The mean age of onset in our
      38 patients was 3.4 months, while the mean age at diagnosis was 31.7 months.
      Apart from recurrent pneumonia and abscesses, tuberculosis (TB) and Bacille
      Calmette-Guerin (BCG) infections were notable features in our cohort. Overall, 17
      cases died and patient 1 did not participate in the follow-up period . In total,
      we identified 29 different CYBB gene mutations in 31 patients. We found NCF1 and
      CYBA mutations in 3 and 2 patients, respectively. In addition, we identified 31
      carriers and prenatally diagnosed 4 CGD and 4 healthy fetuses. CONCLUSIONS: The
      results of our study demonstrate that children with BCG infections or recurrent
      TB infections should have immune function screening tests performed. Moreover,
      newborns with family histories of primary immunodeficiency diseases should avoid
      of BCG vaccination. Molecular analysis is an important tool for identifying
      patients, carriers, and high-risk CGD fetuses.

PMID- 24943882
TI  - Systematic classification of tablet disintegrants by water uptake and force
      development kinetics.
AB  - OBJECTIVE: Water uptake and force development of disintegrating tablets provide a
      high degree of information about the disintegration mechanisms and process
      itself. An apparatus for the simultaneous measurement of water uptake and force
      development of tablets is presented, and the gathered data are analysed. METHODS:
      Flat faced, 10 mm, dibasic calcium phosphate tablets containing 2% disintegrant
      are investigated with the newly constructed apparatus. The force is determined
      with a texture analyser, whereas the water uptake is recorded by a balance.
      Different measurement regimes are compared with each other. Measured curves are
      analysed according to their shape and fitted with a modified Hill equation. KEY
      FINDINGS: Known disintegration mechanisms can be confirmed with the newly
      constructed apparatus - swelling for sodium starch glycolate and croscarmellose
      sodium, and shape recovery for crospovidone disintegrants. Different brands of
      polacrilin potassium act by different mechanisms. All curves could be fitted
      successfully with a modified Hill equation. A novel classification to facilitate
      the appropriate disintegrant selection is presented on basis of the fit
      parameters. CONCLUSION: The new apparatus allows the acquisition of water uptake
      and force data simultaneously. Parameters calculated with the modified Hill
      equation provide a simple way to classify disintegrants according to their
      behaviour.

PMID- 24943883
TI  - A scuba diving direct sediment sampling methodology on benthic transects in
      glacial lakes: procedure description, safety measures, and tests results.
AB  - This work presents an in situ sediment sampling method on benthic transects,
      specifically intended for scientific scuba diver teams. It was originally
      designed and developed to sample benthic surface and subsurface sediments and
      subaqueous soils in glacial lakes up to a maximum depth of 25 m. Tests were
      conducted on the Sabocos and Banos tarns (i.e., cirque glacial lakes) in the
      Spanish Pyrenees. Two 100 m transects, ranging from 24.5 to 0 m of depth in
      Sabocos and 14 m to 0 m deep in Banos, were conducted. In each test, 10 sediment
      samples of 1 kg each were successfully collected and transported to the surface.
      This sampling method proved operative even in low visibility conditions (<2 m).
      Additional ice diving sampling tests were conducted in Sabocos and Truchas tarns.
      This sampling methodology can be easily adapted to accomplish underwater sampling
      campaigns in nonglacial lakes and other continental water or marine environments.

PMID- 24943884
TI  - Chemical Leasing business models and corporate social responsibility.
AB  - Chemical Leasing is a service-oriented business model that shifts the focus from
      increasing sales volume of chemicals towards a value-added approach. Recent pilot
      projects have shown the economic benefits of introducing Chemical Leasing
      business models in a broad range of sectors. A decade after its introduction, the
      promotion of Chemical Leasing is still predominantly done by the public sector
      and international organizations. We show in this paper that awareness-raising
      activities to disseminate information on this innovative business model mainly
      focus on the economic benefits. We argue that selling Chemical Leasing business
      models solely on the grounds of economic and ecological considerations falls
      short of branding it as a corporate social responsibility initiative, which, for
      this paper, is defined as a stakeholder-oriented concept that extends beyond the
      organization's boundaries and is driven by an ethical understanding of the
      organization's responsibility for the impact of its business activities. For the
      analysis of Chemical Leasing business models, we introduce two case studies from
      the water purification and metal degreasing fields, focusing on employees and
      local communities as two specific stakeholder groups of the company introducing
      Chemical Leasing. The paper seeks to demonstrate that Chemical Leasing business
      models can be branded as a corporate social responsibility initiative by
      outlining the vast potential of Chemical Leasing to improve occupational health
      and safety and to strengthen the ability of companies to protect the environment
      from the adverse effects of the chemicals they apply.

PMID- 24943887
TI  - Weighing empirical and hypothetical evidence for assessing potential invasive
      species range limits: a review of the case of Burmese pythons in the USA.
AB  - Range expansion potential is an important consideration for prioritizing
      management actions against an invasive species. Understanding the potential for
      range expansion by invasive reptiles such as the Burmese python can be
      challenging, because the lack of knowledge on fundamental physiological and
      behavioral constraints initially forces reliance on modeling to predict
      hypothetical invasive range potential. Hypothetical predictions for Burmese
      python range limits in the USA have been highly divergent, from only extreme
      South Florida and the extreme southern Gulf edge of Texas to a broad swath over
      the southern third of the continental USA. Empirical observations on python
      thermal tolerances and behavioral abilities to cope with more temperate
      temperatures became evident during a cold spell in December 2009-January 2010. We
      review and highlight important considerations for improving invasive range
      estimation methodology, deciding between competing range predictions, and the
      importance of having, and applying, empirical data to aid in decision making. 

PMID- 24943886
TI  - Carbon emission from global hydroelectric reservoirs revisited.
AB  - Substantial greenhouse gas (GHG) emissions from hydropower reservoirs have been
      of great concerns recently, yet the significant carbon emitters of drawdown area
      and reservoir downstream (including spillways and turbines as well as river
      reaches below dams) have not been included in global carbon budget. Here, we
      revisit GHG emission from hydropower reservoirs by considering reservoir surface
      area, drawdown zone and reservoir downstream. Our estimates demonstrate around
      301.3 Tg carbon dioxide (CO2)/year and 18.7 Tg methane (CH4)/year from global
      hydroelectric reservoirs, which are much higher than recent observations. The sum
      of drawdown and downstream emission, which is generally overlooked, represents 42
      % CO2 and 67 % CH4 of the total emissions from hydropower reservoirs.
      Accordingly, the global average emissions from hydropower are estimated to be 92
      g CO2/kWh and 5.7 g CH4/kWh. Nonetheless, global hydroelectricity could currently
      reduce approximate 2,351 Tg CO2eq/year with respect to fuel fossil plant
      alternative. The new findings show a substantial revision of carbon emission from
      the global hydropower reservoirs.

PMID- 24943888
TI  - A comparative study of abiological granular sludge (ABGS) formation in different
      processes for zinc removal from wastewater.
AB  - Abiological granular sludge (ABGS) formation is a potential and facile strategy
      for improving sludge settling performance during zinc removal from wastewater
      using chemical precipitation. In this study, the effect of pH, seed dosage, and
      flocculant dosage on ABGS formation and treated water quality was investigated.
      Results show that settling velocity of ABGS can reach up to 4.00 cm/s under
      optimal conditions, e.g., pH of 9.0, zinc oxide (ZnO) seeds dosage of 1.5 g/l,
      and polyacrylamide (PAM) dosage of 10 mg/l. More importantly, ABGS formation
      mechanism was investigated in NaOH precipitation process and compared with that
      in bio-polymer ferric sulfate (BPFS)-NaOH precipitation process regarding their
      sludge structure and composition. In the NaOH precipitation process, ABGS
      formation depends on some attractions between particles, such as van der Waals
      attraction and bridging attraction. However, during the BPFS-NaOH sludge
      formation process, steric repulsion becomes dominant due to the adsorption of
      BPFS on ZnO seeds. This repulsion further causes extremely loose structure and
      poor settling performance of BPFS-NaOH sludge.

PMID- 24943889
TI  - Effects of Cutrine-Plus(r) algaecide and predators on wood frog (Lithobates
      sylvaticus) tadpole survival and growth.
AB  - Copper contamination is increasing in many aquatic ecosystems. One mode by which
      copper can be introduced into aquatic ecosystems is as an algaecide, such as
      Cutrine-Plus(r). Using a mesocosm experiment, we examined the effects of Cutrine
      Plus(r) on wood frog (Lithobates sylvaticus) tadpoles. In addition, we examined
      how the presence of a nonnative predator the Western mosquitofish (Gambusia
      affinis) may interact with exposure to Cutrine-Plus(r). Exposure to our low and
      high Cutrine-Plus(r) treatments had a strong negative effect on the wood frog
      tadpoles, and survivorship was greatly decreased in the low treatment, and no
      tadpoles survived in the high treatment. Additionally, the tadpoles that survived
      the low treatment were significantly smaller than those in the control treatment.
      Mosquitofish had no effect on the survivorship or growth of wood frog tadpoles,
      and mosquitofish presence did not have a significant interaction with the Cutrine
      Plus(r) treatments. Cutrine-Plus(r) clearly had a negative effect on wood frog
      tadpoles at the concentrations used in our experiment, which were at and below
      the label-recommended dosages, suggesting that the use of Cutrine-Plus(r) in
      natural ponds may have negative consequences for wood frog populations and
      possibly other amphibians.

PMID- 24943890
TI  - Impact of gold mining associated with mercury contamination in soil, biota
      sediments and tailings in Kenya.
AB  - This work considered the environmental impact of artisanal mining gold activity
      in the Migori-Transmara area (Kenya). From artisanal gold mining, mercury is
      released to the environment, thus contributing to degradation of soil and water
      bodies. High mercury contents have been quantified in soil (140 MUg kg(-1)),
      sediment (430 MUg kg(-1)) and tailings (8,900 MUg kg(-1)), as expected. The
      results reveal that the mechanism for transporting mercury to the terrestrial
      ecosystem is associated with wet and dry depositions. Lichens and mosses, used as
      bioindicators of pollution, are related to the proximity to mining areas. The
      further the distance from mining areas, the lower the mercury levels. This study
      also provides risk maps to evaluate potential negative repercussions. We conclude
      that the Migori-Transmara region can be considered a strongly polluted area with
      high mercury contents. The technology used to extract gold throughout
      amalgamation processes causes a high degree of mercury pollution around this gold
      mining area. Thus, alternative gold extraction methods should be considered to
      reduce mercury levels that can be released to the environment.

PMID- 24943885
TI  - Occurrence and distribution of PCB metabolites in blood and their potential
      health effects in humans: a review.
AB  - In recent years, attention has been directed to chemicals with possible endocrine
      disrupting properties. Polychlorinated biphenyls (PCBs) and their metabolites
      belong to one group of environmental contaminants that have been shown to
      interact with the endocrine system in mammals, including humans. Although recent
      developments have been made in terms of determination of PCB metabolites in blood
      samples, still limited number of studies have been able to elucidate their
      profiles and toxicological and health effects in humans. This review aims to
      evaluate and compare the levels of hydroxylated PCBs (OH-PCBs) and methyl sulfone
      PCBs (MeSO2-PCBs) in blood and their relationship to parent compounds and also
      address the potential risks and adverse health effects in humans. Levels of OH
      PCBs varied between 0.0002 and 1.6 ng g(-1) w/w in human serum/plasma from the
      selected literature, correlating well with ?PCBs. In contrast, ?OH-PCB/?PCB ratio
      in animals did not show a significant correlation, which might suggest that the
      bioaccumulation plays an even more important role in the concentration of OH-PCBs
      compared to PCB metabolism. Highest levels of MeSO2-PCBs were reported in marine
      mammals with high selectivity retention in the liver. Health effects of PCB
      metabolites included carcinogenicity, reproductive impairment, and developmental
      neurotoxicity, being more efficiently transferred to the brain and across the
      placenta from mother to fetus in comparison to the parent PCBs. Based on the lack
      of knowledge on the occurrence and distribution of lower chlorinated OH-PCBs in
      humans, further studies to identify and assess the risks associated to human
      exposure are essential.

PMID- 24943891
TI  - Injury risk among children in motor vehicle crashes: older versus younger
      drivers.
AB  - AIM: To explore the relationship between injury risk among child occupants
      involved in motor vehicle collisions according to the age of the vehicle driver.
      METHODS: The National Automotive Sampling System Crashworthiness Data System 2000
      2009 (n = 10 797) was used to identify demographic, vehicle-, collision- and
      injury-related characteristics among motor vehicle collision occupants <=15 years
      of age. The association between the age of the driver (older vs. younger, defined
      as individuals <50 years of age vs. individuals >=50 years of age, respectively)
      and injury occurrence was estimated using logistic regression adjusting for the
      potentially confounding effect of occupant, vehicle and collision
      characteristics. RESULTS: Of the child occupants in motor vehicle collisions,
      2.9% were driving with an older driver, and approximately 2.9% were injured while
      driving with a younger driver (odds ratio 1.03; 95% confidence interval 0.55
      1.91). After adjusting for child occupant age, gender, restraint use, seat
      position and vehicle type, there remained no significant association between the
      age of the driver (older vs. younger) and the risk of injury (odds ratio 0.92;
      95% confidence interval 0.49-1.74). CONCLUSIONS: These findings add to the body
      of literature indicating no difference in injury risk found among children when
      considering the age of the driver. Research is needed to ascertain the
      association and further evaluate characteristics more specific to the
      relationship being explored in this study.

PMID- 24943892
TI  - Close observation unit to prevent falls and minimize use of patient care
      companions.
AB  - Fall rates and patient companion use were examined after opening a close
      observation unit (COU) for patients with internal medicine diagnoses. Of 2023
      patients (COU, n = 145; internal medicine unit, n = 1878), COU patients had more
      neurologic and psychiatric problems, had a longer mean length of stay, and were
      discharged home less often than internal medicine unit patients. Although COU
      patients had higher acuity, there were no differences between groups in fall
      rates per 100 patient-days and no use of patient companions in the COU.

PMID- 24943893
TI  - Differential high-altitude adaptation and restricted gene flow across a mid
      elevation hybrid zone in Andean tit-tyrant flycatchers.
AB  - The tropical Andes are a global hotspot of avian diversity that is characterized
      by dramatic elevational shifts in community composition and a preponderance of
      recently evolved species. Bird habitats in the Andes span a nearly twofold range
      of atmospheric pressure that poses challenges for respiration, thermoregulation,
      water balance and powered flight, but the extent to which physiological
      constraints limit species' elevational distributions is poorly understood. We
      report a previously unknown hybrid zone between recently diverged flycatchers
      (Aves, Tyrannidae) with partially overlapping elevational ranges. The southern
      Anairetes reguloides has a broad elevational range (0-4200 m), while the northern
      Anairetes nigrocristatus is restricted to high elevations (>2200 m). We found
      hybrids in central Peru at elevations between ~3100 and 3800 m, with A.
      nigrocristatus above this elevation and A. reguloides below. We analysed
      variation in haematology, heart mass, morphometrics, plumage and one
      mitochondrial and three nuclear loci across an elevational transect that
      encompasses the hybrid zone. Phenotypic traits and genetic markers all showed
      steep clines across the hybrid zone. Haemoglobin concentration, haematocrit, mean
      cellular haemoglobin concentration and relative heart mass each increased at
      altitude more strongly in A. reguloides than in A. nigrocristatus. These findings
      suggest that A. nigrocristatus is more resistant than A. reguloides to high
      altitude hypoxic respiratory stress. Considering that the ancestor of the genus
      is suggested to have been restricted to high elevations, A. reguloides may be
      secondarily adapted to low altitude. We conclude that differential respiratory
      specialization on atmospheric pressure combined with competitive exclusion
      maintains replacement along an elevational contour, despite interbreeding. 

PMID- 24943895
TI  - Demixing and crystallization of DODAB in DPPC-DODAB binary mixtures.
AB  - The crystallization mechanism of one lipid component within multicomponent lipid
      mixtures remains unclear. To shed light on this issue, we studied the demixing
      and crystallization behaviors of a binary lipid system using neutral
      dipalmitoylphosphatidylcholine (DPPC) and cationic dioctadecyldimethylammonium
      bromide (DODAB) as model molecules. The results indicate that when DODAB is no
      more than equimolar (e.g., DPPC/DODAB = 2/1 and 1/1), DPPC is miscible with DODAB
      and hinders the crystallization of DODAB, and the samples undergo reversible gel
      fluid phase transitions upon heating and cooling. However, when DODAB is dominant
      in the mixture (DPPC/DODAB = 1/2), cooling of the mixed fluid phase results in
      the formation of a DODAB-rich gel domain and a DPPC-DODAB mixed gel domain. Such
      phase-separated mixed gels can undergo further demixing and crystallization,
      producing a DODAB-rich crystalline domain and a DPPC-rich tilted gel domain upon
      prolonged (or plus low-temperature) incubation. Besides, evidence has been given
      that the crystallized DODAB-rich domain remains in the same lipid bilayer as the
      DPPC-rich domain. All the three binary lipid mixtures can hold large amounts of
      water in the lipid interlamellar regions, allowing the incorporation of a large
      number of water-soluble substances such as DNA or proteins, which can be used for
      the fabrication of functional biofilms and biomaterials. Influences of water
      content and salt concentration on the phase structures (e.g., repeat distances)
      of the binary mixtures have also been studied. 

PMID- 24943894
TI  - 'As above, so below' examining the interplay between emotion and the immune
      system.
AB  - While the concept of a palpable relationship between our mental and physical well
      being is certainly not new, it is only in the light of modern scientific research
      that we have begun to realize how deeply connected our emotional and immune
      states may be. We begin this review with a series of studies demonstrating how
      four fundamental emotional responses: anger, anxiety, mirth and relaxation are
      able modulate cytokine production and cellular responses to a variety of immune
      stimuli. These modulations are shown to be either detrimental or beneficial to a
      patient's health dependent on the context and duration of the emotion. We also
      discuss the reverse, highlighting research demonstrating how the loss of key
      immune cells such as T lymphocytes in clinical and animal studies can negatively
      impact both emotional well-being and cognition. Additionally, to give a more
      complete picture of the manifold pathways that link emotion and the immune
      system, we give a brief overview of the influence the digestive system has upon
      mental and immunological health. Finally, throughout this review we attempt to
      highlight the therapeutic potential of this burgeoning field of research in both
      the diagnosis and treatment of immune and disorders. As well as identifying some
      of the key obstacles the field must address in order to put this potential into
      practice. 

PMID- 24943896
TI  - Hydroxybenzoic acid isomers and the cardiovascular system.
AB  - Today we are beginning to understand how phytochemicals can influence metabolism,
      cellular signaling and gene expression. The hydroxybenzoic acids are related to
      salicylic acid and salicin, the first compounds isolated that have a
      pharmacological activity. In this review we examine how a number of
      hydroxyphenolics have the potential to ameliorate cardiovascular problems related
      to aging such as hypertension, atherosclerosis and dyslipidemia. The compounds
      focused upon include 2,3-dihydroxybenzoic acid (Pyrocatechuic acid), 2,5
      dihydroxybenzoic acid (Gentisic acid), 3,4-dihydroxybenzoic acid (Protocatechuic
      acid), 3,5-dihydroxybenzoic acid (alpha-Resorcylic acid) and 3-monohydroxybenzoic
      acid. The latter two compounds activate the hydroxycarboxylic acid receptors with
      a consequence there is a reduction in adipocyte lipolysis with potential
      improvements of blood lipid profiles. Several of the other compounds can activate
      the Nrf2 signaling pathway that increases the expression of antioxidant enzymes,
      thereby decreasing oxidative stress and associated problems such as endothelial
      dysfunction that leads to hypertension as well as decreasing generalized
      inflammation that can lead to problems such as atherosclerosis. It has been known
      for many years that increased consumption of fruits and vegetables promotes
      health. We are beginning to understand how specific phytochemicals are
      responsible for such therapeutic effects. Hippocrates' dictum of 'Let food be
      your medicine and medicine your food' can now be experimentally tested and the
      results of such experiments will enhance the ability of nutritionists to devise
      specific health-promoting diets. 

PMID- 24943898
TI  - Cleft palate reconstruction using collagen and nanofiber scaffold incorporating
      bone morphogenetic protein in rats.
AB  - BACKGROUND: Absorbable collagen sponge (ACS) loaded with bone morphogenetic
      protein-2 (BMP-2) is approved for selected clinical applications; however, burst
      release limits its widespread use. Therefore, nanofiber (NF)-based scaffold with
      ACS backbone was developed to sustain release of loaded BMP-2 to improve the
      outcomes of bone grafting in a rodent model of cleft palate. METHODS: BMP-2 was
      loaded on ACS scaffold and then NF hydrogel with different densities (1-2%) was
      added to sustain the BMP-2 release. The release profiles of BMP-2 from constructs
      with different NF densities were evaluated in vitro to explore the optimum NF
      density that could recapitulate physiological bone healing process. Subsequently,
      scaffold with the appropriate NF density was implanted into a rodent model of
      cleft palate. Wistar rats, with surgically induced maxillary cleft defects, were
      then assigned to one of the following groups (n=6/group): no scaffold (control),
      ACS, ACS+BMP-2, NF+ACS, and NF+ACS+BMP-2. Micro-computed tomography (MUCT) was
      utilized to evaluate percent bone filling (%BF) at defect site as well as changes
      in anteroposterior and transverse dimensions of the maxilla at weeks 0, 4, and 8.
      Histological assessment of bone healing was performed at week 8. RESULTS: In
      vitro release experiments showed that scaffolds containing 2% NF exhibited a
      release profile conducive to the natural stages of bone healing and, hence, it
      was utilized for subsequent in vivo studies. Bone healing occurred at the defect
      margins leaving a central bone void in the control, ACS, and NF+ACS groups over
      the 8-week study period. BMP-2-treated groups demonstrated higher %BF as compared
      with other groups at week 8 (p<0.05). Whereas the NF+ACS+BMP-2 group showed bone
      bridging of the defect as early as 4 weeks, which was not evident in ACS+BMP-2
      group. In all groups, bone grafts did not disrupt anteroposterior and transverse
      growth of maxilla. Based on histological evaluations together with MUCT data,
      NF+ACS+BMP-2 treatment resulted in clinically significant and consistent bone
      healing throughout the implanted scaffold when compared with the ACS+BMP-2 group.
      CONCLUSION: NF+ACS+BMP-2 constructs exhibited osteoinductive properties together
      with preparation simplicity, which makes it a novel approach for BMP-2 delivery
      for cleft palate reconstruction.

PMID- 24943897
TI  - Mitochondrial biogenesis-associated factors underlie the magnitude of response to
      aerobic endurance training in rats.
AB  - Trainability is important in elite sport and in recreational physical activity,
      and the wide range for response to training is largely dependent on genotype. In
      this study, we compare a newly developed rat model system selectively bred for
      low and high gain in running distance from aerobic training to test whether
      genetic segregation for trainability associates with differences in factors
      associated with mitochondrial biogenesis. Low response trainer (LRT) and high
      response trainer (HRT) rats from generation 11 of artificial selection were
      trained five times a week, 30 min per day for 3 months at 70 % VO2max to study
      the mitochondrial molecular background of trainability. As expected, we found
      significant differential for the gain in running distance between LRT and HRT
      groups as a result of training. However, the changes in VO2max, COX-4, redox
      homeostasis associated markers (reactive oxygen species (ROS)), silent mating
      type information regulation 2 homolog (SIRT1), NAD(+)/NADH ratio, proteasome (R2
      subunit), and mitochondrial network related proteins such as mitochondrial
      fission protein 1 (Fis1) and mitochondrial fusion protein (Mfn1) suggest that
      these markers are not strongly involved in the differences in trainability
      between LRT and HRT. On the other hand, according to our results, we discovered
      that differences in basal activity of AMP-activated protein kinase alpha
      (AMPKalpha) and differential changes in aerobic exercise-induced responses of
      citrate synthase, carbonylated protein, peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC1-alpha), nuclear respiratory factor 1
      (NRF1), mitochondrial transcription factor A (TFAM), and Lon protease limit
      trainability between these selected lines. From this, we conclude that
      mitochondrial biogenesis-associated factors adapt differently to aerobic exercise
      training in training sensitive and training resistant rats.

PMID- 24943900
TI  - Action and language integration: from humans to cognitive robots.
AB  - The topic is characterized by a highly interdisciplinary approach to the issue of
      action and language integration. Such an approach, combining computational models
      and cognitive robotics experiments with neuroscience, psychology, philosophy, and
      linguistic approaches, can be a powerful means that can help researchers
      disentangle ambiguous issues, provide better and clearer definitions, and
      formulate clearer predictions on the links between action and language. In the
      introduction we briefly describe the papers and discuss the challenges they pose
      to future research. We identify four important phenomena the papers address and
      discuss in light of empirical and computational evidence: (a) the role played not
      only by sensorimotor and emotional information but also of natural language in
      conceptual representation; (b) the contextual dependency and high flexibility of
      the interaction between action, concepts, and language; (c) the involvement of
      the mirror neuron system in action and language processing; (d) the way in which
      the integration between action and language can be addressed by developmental
      robotics and Human-Robot Interaction. 

PMID- 24943901
TI  - Non-occupational allergic contact dermatitis caused by azithromycin in an eye
      solution.

PMID- 24943899
TI  - Functional relevance of NLRP3 inflammasome-mediated interleukin (IL)-1beta during
      acute allergic airway inflammation.
AB  - Overall asthmatic symptoms can be controlled with diverse therapeutic agents.
      However, certain symptomatic individuals remain at risk for serious morbidity and
      mortality, which prompts the identification of novel therapeutic targets and
      treatment strategies. Thus, using an adjuvant-free T helper type 2 (Th2) murine
      model, we have deciphered the role of interleukin (IL)-1 signalling during
      allergic airway inflammation (AAI). Because functional IL-1beta depends on
      inflammasome activation we first studied asthmatic manifestations in specific
      inflammasome-deficient [NACHT, LRR and PYD domains-containing protein 3 (NLRP3(-/
      ) ) and apoptosis-associated speck-like protein containing a caspase recruitment
      domain (ASC(-/-) )] and IL-1 receptor type 1(-/-) (IL-1R1(-/-) ) mice on the
      BALB/c background. To verify the onset of disease we assessed cellular
      infiltration in the bronchial regions, lung pathology, airway hyperresponsiveness
      and ovalbumin (OVA)-specific immune responses. In the absence of NLRP3
      inflammasome-mediated IL-1beta release all symptoms of AAI were reduced, except
      OVA-specific immunoglobulin levels. To address whether manipulating IL-1
      signalling reduced asthmatic development, we administered the IL-1R antagonist
      anakinra (Kineret(r)) during critical immunological time-points: sensitization or
      challenge. Amelioration of asthmatic symptoms was only observed when anakinra was
      administered during OVA challenge. Our findings indicate that blocking IL-1
      signalling could be a potential complementary therapy for allergic airway
      inflammation.

PMID- 24943902
TI  - Effect of a state-based incentive programme on the use of electronic health
      records.
AB  - RATIONALE, AIMS AND OBJECTIVES: In 2004, New York passed the Health Care
      Efficiency and Affordability Law for New Yorkers (HEAL NY) Capital Grants
      Program, which was the largest state-based investment in health information
      technology adoption in the United States. We sought to evaluate the effects of
      this programme on electronic health records (EHR) usage. METHODS: We undertook a
      case-control study of health care providers who had signed up with a regional
      extension centre, some of whom had also received HEAL funding through programmes
      intended to support EHR adoption. The outcome of interest was achievement of
      Medicare or Medicaid Meaningful Use and the primary exposure was any link to HEAL
      NY funding. The association between Meaningful Use status and independent
      variables was measured using logistic regression models. RESULTS: Meaningful
      Users were more likely to have had a history of HEAL NY funding (OR=1.83; 95%
      CI=1.59, 2.09). Also, achievement of Meaningful Use was associated with having an
      EHR before 2011 (OR=1.64; 95% CI=146, 1.83). Among those with EHRs prior to 2011,
      the odds of achieving Meaningful Use were statistically higher if coupled with
      HEAL NY funding (OR=3.12; 95% CI=2.50, 3.90). CONCLUSION: Achieving Meaningful
      Use was associated with a history of HEAL NY funding. However, it was the
      combination of HEAL NY funding and historic usage of EHRs that was associated
      with the largest increase in the odds that the provider was a Meaningful User.
      These findings indicate that state-based incentive programmes can support the
      effective usage of health information technologies.

PMID- 24943903
TI  - Microscopic analysis of a native Bacillus thuringiensis strain from Malaysia that
      produces exosporium-enclosed parasporal inclusion.
AB  - The current study focused on the microscopic studies of a native Bacillus
      thuringiensis strain isolated from Malaysia, Bt-S84-13a, that produced an unusual
      crystal type. Primary detection of parasporal inclusions using a phase contrast
      microscope presented one to two small crystal proteins in the sporulating cells
      of Bt-S84-13a. Compound light microscopic examination of autolysed Bt-S84-13a
      cells stained with 0.133% Coomassie Brilliant Blue showed two types of crystal
      morphology: small crystals independent of spores and spore-associated crystals.
      Surface structure analysis with a scanning electron microscope revealed spherical
      like, coarse and wrinkled-looking crystal in Bt-S84-13a. A close-up observation
      of the crystal morphology using a transmission electron microscope also
      demonstrated two parasporal inclusions in Bt-S84-13a. One inclusion was deposited
      against the forespore and was in a shape of incomplete rectangular. Another
      smaller inclusion was developed within the exosporium and was rectangular in
      shape. However, the latter inclusion was found lack in another bacterial cell
      which was still in the early stages of sporulation. This unique crystal
      morphology may imply some biological potential in Bt-S84-13a. 

PMID- 24943904
TI  - Ab interno approach to the subconjunctival space using a collagen glaucoma stent.
AB  - This review considers a minimally invasive ab interno approach to glaucoma
      filtration surgery. Glaucoma filtration surgery can be defined as an attempt to
      lower intraocular pressure (IOP) by the surgical formation of an artificial
      drainage pathway from the anterior chamber to the subconjunctival space.
      Subconjunctival drainage of aqueous fluid has been a cornerstone of glaucoma
      surgery for more than a century. Varying techniques have been deployed to provide
      access to this space. Yet, despite numerous innovations in filtering surgery to
      achieve safe IOP reduction, too many short-term and long-term complications are
      associated with this surgery. This article describes the development of a new,
      soft, and permanent ab interno collagen implant (XEN gel stent) to optimize
      aqueous drainage to the subconjunctival space. Specific characteristics are
      critical in designing such an implant. Determining the optimum size of the device
      lumen to avoid hypotony while maximizing long-term outflow is crucial. Other
      topics discussed include material, length, diameter, flexibility, stability, and
      biocompatibility of the implant. Preclinical and human eye testing shows that the
      implant does not seem to occlude inside the lumen and the implant material does
      not appear to cause tissue reaction in the eye. The ab interno placement of the
      stent offers an alternative for lowering IOP with a minimally invasive procedure,
      minimum conjunctival tissue disruption, restricted flow to avoid hypotony, and
      long-term safety. FINANCIAL DISCLOSURE: Dr. Lewis received financial support from
      Aquesys, Inc. as a consultant.

PMID- 24943905
TI  - Anatomic and physiologic rationale to be applied in accessing the suprachoroidal
      space for management of glaucoma.
AB  - This review examines the anatomic and physiologic rationale for accessing the
      suprachoroidal space in the management of glaucoma. The potential benefits and
      limitations of past and present attempts to tap into the intraocular pressure
      lowering effects of the suprachoroidal space are highlighted. FINANCIAL
      DISCLOSURE: The author has no financial or proprietary interest in any material
      or method mentioned.

PMID- 24943906
TI  - Is brain natriuretic peptide a reliable biomarker of hydration status in all
      peritoneal dialysis patients?
AB  - BACKGROUND: Achievement of euvolemia is a fundamental challenge in the peritoneal
      dialysis (PD) population. Bioimpedance spectroscopy (BIS) is one of the best
      techniques for routine assessment of hydration status (HS) in PD, but in recent
      years, the role of brain natriuretic peptides (BNP) in the assessment of volume
      status has gained interest. The aim of this study was to investigate the relation
      between BNP and volume status as measured by BIS in PD patients and to assess how
      these variables correlate according to the time that a patient has been on PD.
      METHODS: We prospectively studied 68 PD patients from whom measurements of BNP
      and assessments of HS by BIS were performed every 3 months. Three groups were
      defined based on HS: group A, measurements of HS <-1.1 liters (underhydrated);
      group B, measurements of HS between -1.1 and +1.1 liters (normohydrated), and
      group C, measurements of HS >+1.1 liters (overhydrated). Measurements were also
      separated according to the time on PD (<6 vs. >=6 months). Correlation between HS
      and BNP was performed using Spearman's correlation. RESULTS: We performed a total
      of 478 measurements of HS and BNP. There was a statistically significant
      difference in BNP (p < 0.001) among three HS groups, with higher levels of BNP
      detected in overhydrated patients. We found a positive correlation between HS and
      BNP (rs = 0.28; p <0.001) that seemed stronger in the first 6 months on PD (rs =
      0.42; p = 0.006). CONCLUSIONS: BNP correlated positively with fluid overload
      measured by HS, and this correlation was stronger in the first 6 months on PD.

PMID- 24943907
TI  - The role of egocentric and allocentric abilities in Alzheimer's disease: a
      systematic review.
AB  - A great effort has been made to identify crucial cognitive markers that can be
      used to characterize the cognitive profile of Alzheimer's disease (AD). Because
      topographical disorientation is one of the earliest clinical manifestation of AD,
      an increasing number of studies have investigated the spatial deficits in this
      clinical population. In this systematic review, we specifically focused on
      experimental studies investigating allocentric and egocentric deficits to
      understand which spatial cognitive processes are differentially impaired in the
      different stages of the disease. First, our results highlighted that spatial
      deficits appear in the earliest stages of the disease. Second, a need for a more
      ecological assessment of spatial functions will be presented. Third, our analysis
      suggested that a prevalence of allocentric impairment exists. Specifically, two
      selected studies underlined that a more specific impairment is found in the
      translation between the egocentric and allocentric representations. In this
      perspective, the implications for future research and neurorehabilitative
      interventions will be discussed. 

PMID- 24943908
TI  - Reactive oxygen species contribute to simulated ischemia/reperfusion-induced
      autophagic cell death in human umbilical vein endothelial cells.
AB  - BACKGROUND: Autophagy is important for cells to degrade protein aggregates and
      organelles. Our preliminary study suggests that ischemia/reperfusion in rabbit
      hearts promoted autophagic myocardial injury, resulting in no-reflow phenomenon.
      In this study, we sought to further understand the mechanism and outcome of the
      upregulation of autophagy in ischemia/reperfusion. MATERIAL AND METHODS: We
      employed a simulated ischemia/reperfusion (sI/R) model in human umbilical vein
      endothelial cells (HUVECs) in vitro, in the presence or absence of antioxidants.
      RESULTS: Our study confirms that sI/R induces autophagy in HUVECs as measured by
      increased expression of Beclin 1 and microtubule-associated protein 1 light chain
      3 (LC3), electron microscopic analysis, and special biofluorescent staining with
      monodansylcadaverine. This sI/R-induced autophagy was also accompanied by
      increased levels of p65 protein expression and cell death. In addition, we
      detected the accumulation of reactive oxygen species (ROS) after sI/R. Moreover,
      with the application of ROS scavengers that block the release of ROS, we were
      able to demonstrate that inhibition of autophagy increases cell survival.
      CONCLUSIONS: The study suggests that ROS accumulation is involved in the sI/R
      induced autophagic cell death in HUVECs.

PMID- 24943909
TI  - Characteristics and outcomes of varied treatment modalities for partially
      thrombosed intracranial aneurysms: a review of 35 cases.
AB  - OBJECTIVE: The purpose of this study was to analyze the characteristics of
      partially thrombosed intracranial aneurysms (PTIAs) in terms of location, shape,
      size, and symptoms, and to assess outcome according to the type of treatment.
      METHODS: We reviewed the radiological and clinical findings of 35 cases of PTIAs
      followed in our institution between 2006 and 2011. We divided all treatment
      modalities into two groups. Patients in group A (n = 15) were treated by blood
      flow blockage from the lesion of the pathogenic segment of the parent where the
      PTIAs originated, and patients in group B (n = 20) were only treated with
      obliteration of the remnant perfused aneurysmal sac. Radiological and clinical
      outcomes of treatment were compared between the two groups. RESULTS: Group A
      showed complete occlusion in 15 cases (100 %) compared to six cases (30.0 %) in
      group B (p < 0.001). No cases required retreatment in group A, while six cases
      (30.0 %) underwent retreatment in group B (p = 0.027). In terms of clinical
      outcome, 12 cases (80.0 %) showed symptomatic improvement in group A compared to
      eight cases (40.0 %) in group B (p = 0.037). Nine cases (60.0 %) showed
      improvement in postoperative GOS at six months compared to initial preoperative
      GOS in group A versus four (20.0 %) in group B (p = 0.032). CONCLUSION: PTIAs
      should be treated by preventing blood flow from the lesion of the pathogenic
      segment of the parent artery where PTIAs originate. This treatment approach is
      associated with better clinical and radiological outcomes.

PMID- 24943910
TI  - Risk factors of delayed surgical evacuation for initially nonoperative acute
      subdural hematomas following mild head injury.
AB  - BACKGROUND: Although the majority of patients with minimal acute subdural
      hematomas (aSDHs) can be managed conservatively, some require delayed aSDH
      evacuation due to hematoma enlargement. This study was designed to determine the
      risk factors associated with delayed hematoma enlargement leading to surgery in
      patients with aSDHs who did not initially require surgical intervention. METHODS:
      From 2002 to 2012, 98 patients were treated for nonoperative aSDHs following mild
      head injury (Glasgow Coma Scale scores of 13-15). The outcome variables were
      radiographic evidence of SDH enlargement on serially obtained computed tomography
      (CT) images and later surgical evacuation. Univariate and multivariate analyses
      were applied to both the demographic and initial radiographic features to
      identify risk factors for SDH progression and surgery. RESULTS: Overall, 64
      patients (65 %) revealed minimal SDH or spontaneous hematoma resolution
      (conservative group) with conservative management at their last follow-up CT
      scan. The remaining 34 patients (35 %) received delayed hematoma evacuation
      (delayed surgery group) a median of 17 days after the head trauma. There were no
      significant differences between the two groups for baseline characteristics,
      including age, injury type, degree of brain atrophy, prior history of
      antithrombotic drugs, and coagulopathy. The presence of cerebral contusions and
      subarachnoid hemorrhages was more common in the conservative group (p = 0.003 and
      p = 0.003, respectively). On multivariate analysis, hematoma volume (p = 0.01,
      odds ratio [OR] = 1.094, 95 % confidence interval [CI] = 1.021-1.173) and degree
      of midline shift (p = 0.01, OR = 1.433, 95 % CI = 1.088-1.888) on the initial CT
      scan were independently associated with delayed hematoma evacuation. CONCLUSIONS:
      A critical proportion of patients with minimal aSDHs occurring after mild head
      injury can progress over several weeks and require hematoma evacuation.
      Especially patients with a large initial SDH volume and accompanying midline
      shift require careful monitoring of hematoma progression.

PMID- 24943911
TI  - The X-ray structure of the complex formed in the reaction between oxaliplatin and
      lysozyme.
AB  - The X-ray structure of the adduct formed between oxaliplatin and the model
      protein hen egg white lysozyme is reported here. The structure is compared with
      those of cisplatin and carboplatin derivatives, previously solved. Relevant
      changes are highlighted among these crystal structures that are suggestive of
      significant differences in the reactivity of platinum drugs with this protein;
      possible biological implications are discussed. 

PMID- 24943912
TI  - Automated Cellient(TM) cytoblocks: better, stronger, faster?
AB  - OBJECTIVE: Cytoblocks (CBs), or cell blocks, provide additional morphological
      detail and a platform for immunocytochemistry (ICC) in cytopathology. The
      Cellient(TM) system produces CBs in 45 minutes using methanol fixation, compared
      with traditional CBs, which require overnight formalin fixation. This study
      compares Cellient and traditional CB methods in terms of cellularity, morphology
      and immunoreactivity, evaluates the potential to add formalin fixation to the
      Cellient method for ICC studies and determines the optimal sectioning depth for
      maximal cellularity in Cellient CBs. METHODS: One hundred and sixty CBs were
      prepared from 40 cytology samples (32 malignant, eight benign) using four
      processing methods: (A) traditional; (B) Cellient (methanol fixation); (C)
      Cellient using additional formalin fixation for 30 minutes; (D) Cellient using
      additional formalin fixation for 60 minutes. Haematoxylin and eosin-stained
      sections were assessed for cellularity and morphology. ICC was assessed on 14
      cases with a panel of antibodies. Three additional Cellient samples were serially
      sectioned to determine the optimal sectioning depth. Scoring was performed by two
      independent, blinded reviewers. RESULTS: For malignant cases, morphology was
      superior with Cellient relative to traditional CBs (P < 0.001). Cellularity was
      comparable across all methods. ICC was excellent in all groups and the addition
      of formalin at any stage during the Cellient process did not influence the
      staining quality. Serial sectioning through Cellient CBs showed optimum
      cellularity at 30-40 MUm with at least 27 sections obtainable. CONCLUSIONS:
      Cellient CBs provide superior morphology to traditional CBs and, if required,
      formalin fixation may be added to the Cellient process for ICC. Optimal Cellient
      CB cellularity is achieved at 30-40 MUm, which will impact on the handling of
      cases in daily practice.

PMID- 24943914
TI  - The "PErFecTED technique": proximal embolization first, then embolize distal for
      benign prostatic hyperplasia.
AB  - Prostatic artery embolization requires a refined technique to achieve good
      imaging and clinical success. The PErFecTED (Proximal Embolization First, Then
      Embolize Distal) technique has produced greater prostate ischemia and infarction
      than previously described methods with clinical improvement of lower urinary
      symptoms and lower recurrence rates. The microcatheter should cross any
      collateral branch to the bladder, rectum, corpus cavernosum, gonad, or penis and
      be placed distally into the prostatic artery before its branching to the central
      gland and peripheral zone. This technique allows better distribution of embolic
      material in the intraprostatic arteries and reduces risk of spasm or thrombus.
      Because benign prostatic hyperplasia develops primarily in the periurethral
      region of the prostate, the urethral group of arteries should be embolized first.
      Subsequent distal investigation and embolization completes occlusion and stasis
      of blood flow to the prostatic parenchyma. Since we added the second step to the
      PErFecTED technique, we have observed infarcts in all patients submitted to
      prostatic artery embolization. 

PMID- 24943915
TI  - The editors' medal 2014.

PMID- 24943913
TI  - Coordination of the filament stabilizing versus destabilizing activities of
      cofilin through its secondary binding site on actin.
AB  - Cofilin is a ubiquitous modulator of actin cytoskeleton dynamics that can both
      stabilize and destabilize actin filaments depending on its concentration and/or
      the presence of regulatory co-factors. Three charge-reversal mutants of yeast
      cofilin, located in cofilin's filament-specific secondary binding site, were
      characterized in order to understand why disruption of this site leads to
      enhanced filament disassembly. Crystal structures of the mutants showed that the
      mutations specifically affect the secondary actin-binding interface, leaving the
      primary binding site unaltered. The mutant cofilins show enhanced activity
      compared to wild-type cofilin in severing and disassembling actin filaments.
      Electron microscopy and image analysis revealed long actin filaments in the
      presence of wild-type cofilin, while the mutants induced many short filaments,
      consistent with enhanced severing. Real-time fluorescence microscopy of labeled
      actin filaments confirmed that the mutants, unlike wild-type cofilin, were
      functioning as constitutively active severing proteins. In cells, the mutant
      cofilins delayed endocytosis, which depends on rapid actin turnover. We conclude
      that mutating cofilin's secondary actin-binding site increases cofilin's ability
      to sever and de-polymerize actin filaments. We hypothesize that activators of
      cofilin severing, like Aip1p, may act by disrupting the interface between
      cofilin's secondary actin-binding site and the actin filament.

PMID- 24943916
TI  - "Squid-capture" modified in situ stent-graft fenestration technique for aortic
      arch aneurysm repair.
AB  - An 83-year-old female was found to have an fusiform aneurysm in the aortic arch.
      She was deemed to be a high surgical risk; therefore, endovascular stent-graft
      placement followed by revascularization of the brachiocephalic trunk using in
      situ stent-graft fenestration was considered. However, the safe application of
      fenestration was deemed difficult due to the tortuosity of the brachiocephalic
      artery. The patient was successfully treated with the aid of the "squid-capture"
      technique, which consists of deployment of the stent-graft in a snare wire loop
      that was advanced from the brachiocephalic artery and fenestration of the stent
      graft with the support of the loop. A follow-up exam revealed complete sealing of
      the aneurysm without any complications. The squid-capture technique allows for
      the safe and secure puncture of the graft. 

PMID- 24943917
TI  - Retraction of statins article is not in the public interest: better
      characterisation of benefits and risks is crucial.

PMID- 24943919
TI  - The use of segmented regression in analysing interrupted time series studies: an
      example in pre-hospital ambulance care.
AB  - BACKGROUND: An interrupted time series design is a powerful quasi-experimental
      approach for evaluating effects of interventions introduced at a specific point
      in time. To utilize the strength of this design, a modification to standard
      regression analysis, such as segmented regression, is required. In segmented
      regression analysis, the change in intercept and/or slope from pre- to post
      intervention is estimated and used to test causal hypotheses about the
      intervention. We illustrate segmented regression using data from a previously
      published study that evaluated the effectiveness of a collaborative intervention
      to improve quality in pre-hospital ambulance care for acute myocardial infarction
      (AMI) and stroke. In the original analysis, a standard regression model was used
      with time as a continuous variable. We contrast the results from this standard
      regression analysis with those from segmented regression analysis. We discuss the
      limitations of the former and advantages of the latter, as well as the challenges
      of using segmented regression in analysing complex quality improvement
      interventions. FINDINGS: Based on the estimated change in intercept and slope
      from pre- to post-intervention using segmented regression, we found insufficient
      evidence of a statistically significant effect on quality of care for stroke,
      although potential clinically important effects for AMI cannot be ruled out.
      CONCLUSIONS: Segmented regression analysis is the recommended approach for
      analysing data from an interrupted time series study. Several modifications to
      the basic segmented regression analysis approach are available to deal with
      challenges arising in the evaluation of complex quality improvement
      interventions.

PMID- 24943920
TI  - Methyl jasmonate affects phenolic metabolism and gene expression in blueberry
      (Vaccinium corymbosum).
AB  - Blueberry (Vaccinium corymbosum) is a fruit very much appreciated by consumers
      for its antioxidant potential and health-promoting traits. Its beneficial
      potential properties are mainly due to a high content of anthocyanins and their
      amount can change after elicitation with methyl jasmonate. The aim of this work
      is to evaluate the changes in expression of several genes, accumulation of
      phenolic compounds and alterations in antioxidant potential in two different
      blueberry cultivars ('Duke' and 'Blueray') in response to methyl jasmonate (0.1
      mM). Results showed that 9 h after treatment, the expression of phenylalanine
      ammonium lyase, chalcone synthase and anthocyanidin synthase genes was stimulated
      more in the 'Blueray' variety. Among the phenols measured an increase was
      recorded also for epicatechin and anthocyanin concentrations. 'Duke' is a richer
      sourche of anthocyanins compared to 'Blueray', treatment with methyl jasmonate
      promoted in 'Blueray' an increase in pigments as well as in the antioxidant
      potential, especially in fully ripe berries, but treated 'Duke' berries had
      greater levels, which were not induced by methyl jasmonate treatment. In
      conclusion, methyl jasmonate was, in some cases, an effective elicitor of
      phenolic metabolism and gene expression in blueberry, though with different
      intensity between cultivars. 

PMID- 24943918
TI  - The effects of mindfulness-based stress reduction on objective and subjective
      sleep parameters in women with breast cancer: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of
      mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)) on
      multiple measures of objective and subjective sleep parameters among breast
      cancer survivors (BCS). METHODS: Data were collected using a two-armed randomized
      controlled design among BCS enrolled in either a 6-week MBSR(BC) program or a
      usual care (UC) group with a 12-week follow-up. The present analysis is a subset
      of the larger parent trial (ClinicalTrials.gov Identifier: NCT01177124). Seventy
      nine BCS participants (mean age 57 years), stages 0-III, were randomly assigned
      to either the formal (in-class) 6-week MBSR(BC) program or UC. Subjective sleep
      parameters (SSP) (i.e., sleep diaries and the Pittsburgh Sleep Quality Index
      (PSQI)) and objective sleep parameters (OSP) (i.e., actigraphy) were measured at
      baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) or UC program.
      RESULTS: Results showed indications of a positive effect of MBSR(BC) on OSP at 12
      weeks on sleep efficiency (78.2% MBSR(BC) group versus 74.6% UC group, p = 0.04),
      percent of sleep time (81.0% MBSR(BC) group versus 77.4% UC group, p = 0.02), and
      less number waking bouts (93.5 in MBSR(BC) group versus 118.6 in the UC group, p
      < 0.01). Small nonsignificant improvements were found in SSP in the MBSR(BC)
      group from baseline to 6 weeks (PSQI total score, p = 0.09). No significant
      relationship was observed between minutes of MBSR(BC) practice and SSP or OSP.
      CONCLUSIONS: These data suggest that MBSR(BC) may be an efficacious treatment to
      improve objective and subjective sleep parameters in BCS.

PMID- 24943921
TI  - Dermal xenobiotic metabolism: a comparison between native human skin, four in
      vitro skin test systems and a liver system.
AB  - The xenobiotic metabolism of 4 in vitro human skin test systems (2D and 3D) was
      compared with that of the native human skin samples from which the skin test
      systems had been produced. In total 3 skin samples were investigated, each from a
      different donor to exclude variability due to gender, donor or tissue supplier.
      In addition, the skin cultures were compared with a surrogate of the liver. Basal
      and induced phase I and phase II enzymes were analyzed regarding gene/protein
      expression as well as enzyme activity. The distinctions between the different
      test systems and the two dermal compartments (epidermis and dermis) were more
      noticeable than any donor variability. The 3D models of skin and liver mirrored
      the in vivo situation more realistically than did the monolayer cultures. Phase I
      metabolism was more pronounced in the hepatic model, whereas phase II metabolism
      was more prominent in the reconstructed skin. These results show that
      reconstructed skin models are a valuable tool for organ-specific safety
      assessment with regard to xenobiotic metabolism.

PMID- 24943922
TI  - Tagging live cells that express specific peptidase activity with solid-state
      fluorescence.
AB  - A three-component probe harnesses the extraordinary properties of a solid-state
      fluorophore for the detection of living cells exhibiting a particular peptidase
      activity. The off-on mode by which the probe operates, the bright fluorescence of
      the resulting precipitate, and the rapid response allow an exceptional signal-to
      background ratio during microscopic imaging. A tertiary carbamate link between
      the spacer and phenolic fluorophore is at the heart of the probe's long-term
      stability. The degree of chlorination of the probe determines its response time
      and thus its suitability for live-cell analysis. Our probe also allows highly
      resolved localization of peptidase activity during gel analysis or on agar. In
      comparison, probes releasing soluble fluorophores demonstrate complete diffusion
      of the fluorescent signal. These results demonstrate the probe's potential for
      diverse biomedical applications, including high-fidelity flow cytometry and
      sensitive colony assays. 

PMID- 24943925
TI  - Uprooting researchers can drive them out of science.

PMID- 24943936
TI  - 3D images remodel history.

PMID- 24943923
TI  - Mycophenolate mofetil use after unrelated hematopoietic stem cell transplantation
      for prophylaxis and treatment of graft-vs.-host disease in adult patients in
      Japan.
AB  - Our previous study of 301 patients who received hematopoietic stem cell
      transplantation (HSCT) from related donors demonstrated the efficacy of
      mycophenolate mofetil (MMF) for prophylaxis and treatment of graft-vs.-host
      disease (GVHD). In this study, we investigated the safety and efficacy of MMF in
      716 adult patients who received unrelated HSCT. The incidences of Grade II-IV and
      III-IV acute GVHD in the prophylactic administration group were 38.3% and 14.3%,
      respectively. These rates were not statistically significant when evaluating the
      MMF dosage and graft source. The incidences of limited and extensive chronic GVHD
      were 16.6% and 11.1%, respectively. In the therapeutic administration group,
      69.1% of the subjective symptoms for both acute and chronic GVHD improved. With
      respect to the adverse events, 75 infections and 50 cases of diarrhea were
      observed, and the frequency of these events increased with increasing MMF dose.
      The overall survival rate was 36.4% after a median follow-up period of three yr.
      This study shows that MMF is safe and effective for the prevention and treatment
      of GVHD in patients who have received HSCT from unrelated donors. 

PMID- 24943937
TI  - Tree hitched a ride to island.

PMID- 24943938
TI  - US child study hits buffers.

PMID- 24943939
TI  - HIV trial attacked.

PMID- 24943940
TI  - Irish university labs face external audits.

PMID- 24943941
TI  - The parched planet: water on tap.

PMID- 24943942
TI  - Scientific publishing: the inside track.

PMID- 24943945
TI  - NIH policy: status quo is also costly.

PMID- 24943946
TI  - Open access: sharing your data is easier than you think.

PMID- 24943947
TI  - NIH policy: mandate goes too far.

PMID- 24943948
TI  - Colour blindness: still too many red-green figures.

PMID- 24943949
TI  - Citizen campaigns: justifying embryo research in Europe.

PMID- 24943950
TI  - Applied mathematics: how chaos forgets and remembers.

PMID- 24943951
TI  - Quantum physics: feel the force.

PMID- 24943952
TI  - Measurement of the magnetic interaction between two bound electrons of two
      separate ions.
AB  - Electrons have an intrinsic, indivisible, magnetic dipole aligned with their
      internal angular momentum (spin). The magnetic interaction between two electronic
      spins can therefore impose a change in their orientation. Similar dipolar
      magnetic interactions exist between other spin systems and have been studied
      experimentally. Examples include the interaction between an electron and its
      nucleus and the interaction between several multi-electron spin complexes. The
      challenge in observing such interactions for two electrons is twofold. First, at
      the atomic scale, where the coupling is relatively large, it is often dominated
      by the much larger Coulomb exchange counterpart. Second, on scales that are
      substantially larger than the atomic, the magnetic coupling is very weak and can
      be well below the ambient magnetic noise. Here we report the measurement of the
      magnetic interaction between the two ground-state spin-1/2 valence electrons of
      two (88)Sr(+) ions, co-trapped in an electric Paul trap. We varied the ion
      separation, d, between 2.18 and 2.76 micrometres and measured the electrons'
      weak, millihertz-scale, magnetic interaction as a function of distance, in the
      presence of magnetic noise that was six orders of magnitude larger than the
      magnetic fields the electrons apply on each other. The cooperative spin dynamics
      was kept coherent for 15 seconds, during which spin entanglement was generated,
      as verified by a negative measured value of -0.16 for the swap entanglement
      witness. The sensitivity necessary for this measurement was provided by
      restricting the spin evolution to a decoherence-free subspace that is immune to
      collective magnetic field noise. Our measurements show a d(-3.0(4)) distance
      dependence for the coupling, consistent with the inverse-cube law.

PMID- 24943955
TI  - Possible control of subduction zone slow-earthquake periodicity by silica
      enrichment.
AB  - Seismic and geodetic observations in subduction zone forearcs indicate that slow
      earthquakes, including episodic tremor and slip, recur at intervals of less than
      six months to more than two years. In Cascadia, slow slip is segmented along
      strike and tremor data show a gradation from large, infrequent slip episodes to
      small, frequent slip events with increasing depth of the plate interface.
      Observations and models of slow slip and tremor require the presence of near
      lithostatic pore-fluid pressures in slow-earthquake source regions; however,
      direct evidence of factors controlling the variability in recurrence times is
      elusive. Here we compile seismic data from subduction zone forearcs exhibiting
      recurring slow earthquakes and show that the average ratio of compressional (P)
      wave velocity to shear (S)-wave velocity (vP/vS) of the overlying forearc crust
      ranges between 1.6 and 2.0 and is linearly related to the average recurrence time
      of slow earthquakes. In northern Cascadia, forearc vP/vS values decrease with
      increasing depth of the plate interface and with decreasing tremor-episode
      recurrence intervals. Low vP/vS values require a large addition of quartz in a
      mostly mafic forearc environment. We propose that silica enrichment varying from
      5 per cent to 15 per cent by volume from slab-derived fluids and upward
      mineralization in quartz veins can explain the range of observed vP/vS values as
      well as the downdip decrease in vP/vS. The solubility of silica depends on
      temperature, and deposition prevails near the base of the forearc crust. We
      further propose that the strong temperature dependence of healing and
      permeability reduction in silica-rich fault gouge via dissolution-precipitation
      creep can explain the reduction in tremor recurrence time with progressive silica
      enrichment. Lower gouge permeability at higher temperatures leads to faster fluid
      overpressure development and low effective fault-normal stress, and therefore
      shorter recurrence times. Our results also agree with numerical models of slip
      stabilization under fault zone dilatancy strengthening caused by decreasing fluid
      pressure as pore space increases. This implies that temperature-dependent silica
      deposition, permeability reduction and fluid overpressure development control
      dilatancy and slow-earthquake behaviour. 

PMID- 24943954
TI  - Metastable liquid-liquid transition in a molecular model of water.
AB  - Liquid water's isothermal compressibility and isobaric heat capacity, and the
      magnitude of its thermal expansion coefficient, increase sharply on cooling below
      the equilibrium freezing point. Many experimental, theoretical and computational
      studies have sought to understand the molecular origin and implications of this
      anomalous behaviour. Of the different theoretical scenarios put forward, one
      posits the existence of a first-order phase transition that involves two forms of
      liquid water and terminates at a critical point located at deeply supercooled
      conditions. Some experimental evidence is consistent with this hypothesis, but no
      definitive proof of a liquid-liquid transition in water has been obtained to
      date: rapid ice crystallization has so far prevented decisive measurements on
      deeply supercooled water, although this challenge has been overcome recently.
      Computer simulations are therefore crucial for exploring water's structure and
      behaviour in this regime, and have shown that some water models exhibit liquid
      liquid transitions and others do not. However, recent work has argued that the
      liquid-liquid transition has been mistakenly interpreted, and is in fact a liquid
      crystal transition in all atomistic models of water. Here we show, by studying
      the liquid-liquid transition in the ST2 model of water with the use of six
      advanced sampling methods to compute the free-energy surface, that two metastable
      liquid phases and a stable crystal phase exist at the same deeply supercooled
      thermodynamic condition, and that the transition between the two liquids
      satisfies the thermodynamic criteria of a first-order transition. We follow the
      rearrangement of water's coordination shell and topological ring structure along
      a thermodynamically reversible path from the low-density liquid to cubic ice. We
      also show that the system fluctuates freely between the two liquid phases rather
      than crystallizing. These findings provide unambiguous evidence for a liquid
      liquid transition in the ST2 model of water, and point to the separation of time
      scales between crystallization and relaxation as being crucial for enabling it. 

PMID- 24943953
TI  - Ultrafast X-ray probing of water structure below the homogeneous ice nucleation
      temperature.
AB  - Water has a number of anomalous physical properties, and some of these become
      drastically enhanced on supercooling below the freezing point. Particular
      interest has focused on thermodynamic response functions that can be described
      using a normal component and an anomalous component that seems to diverge at
      about 228 kelvin (refs 1-3). This has prompted debate about conflicting theories
      that aim to explain many of the anomalous thermodynamic properties of water. One
      popular theory attributes the divergence to a phase transition between two forms
      of liquid water occurring in the 'no man's land' that lies below the homogeneous
      ice nucleation temperature (TH) at approximately 232 kelvin and above about 160
      kelvin, and where rapid ice crystallization has prevented any measurements of the
      bulk liquid phase. In fact, the reliable determination of the structure of liquid
      water typically requires temperatures above about 250 kelvin. Water
      crystallization has been inhibited by using nanoconfinement, nanodroplets and
      association with biomolecules to give liquid samples at temperatures below TH,
      but such measurements rely on nanoscopic volumes of water where the interaction
      with the confining surfaces makes the relevance to bulk water unclear. Here we
      demonstrate that femtosecond X-ray laser pulses can be used to probe the
      structure of liquid water in micrometre-sized droplets that have been
      evaporatively cooled below TH. We find experimental evidence for the existence of
      metastable bulk liquid water down to temperatures of 227(-1)(+2) kelvin in the
      previously largely unexplored no man's land. We observe a continuous and
      accelerating increase in structural ordering on supercooling to approximately 229
      kelvin, where the number of droplets containing ice crystals increases rapidly.
      But a few droplets remain liquid for about a millisecond even at this
      temperature. The hope now is that these observations and our detailed structural
      data will help identify those theories that best describe and explain the
      behaviour of water.

PMID- 24943959
TI  - Prevalence and risk factor assessment of Tropheryma whipplei in a rural community
      in Gabon: a community-based cross-sectional study.
AB  - Tropheryma whipplei is the causative agent of Whipple's disease and has been
      detected in stools of asymptomatic carriers. Colonization has been associated
      with precarious hygienic conditions. There is a lack of knowledge about the
      epidemiology and transmission characteristics on a population level, so the aim
      of this study was to determine the overall and age-specific prevalence of T.
      whipplei and to identify risk factors for colonization. This molecular
      epidemiological survey was designed as a cross-sectional study in a rural
      community in Central African Gabon and inhabitants of the entire community were
      invited to participate. Overall prevalence assessed by real-time PCR and
      sequencing was 19.6% (95% CI 16-23.2%, n=91) in 465 stool samples provided by the
      study participants. Younger age groups showed a significantly higher prevalence
      of T. whipplei colonization ranging from 40.0% (95% CI 27.8-52.2) among the 0-4
      year olds to 36.4% (95% CI 26.1-46.6) among children aged 5-10 years. Prevalence
      decreased in older age groups (p<0.001) from 12.6% (95% CI 5.8-19.4%; 11-20
      years) to 9.7% (95% CI 5.7-13.6) among those older than 20. Risk factor analysis
      revealed young age, male sex, and number of people sharing a bed as factors
      associated with an increased risk for T. whipplei carriage. These results
      demonstrate that T. whipplei carriage is highly prevalent in this part of Africa.
      The high prevalence in early life and the analysis of risk factors suggest that
      transmission may peak during childhood facilitated through close person-to-person
      contacts.

PMID- 24943960
TI  - Psychological stress and asthma: a new enemy within.

PMID- 24943961
TI  - Mobile phones support adherence and retention of indigenous participants in a
      randomised controlled trial: strategies and lessons learnt.
AB  - BACKGROUND: Ensuring adherence to treatment and retention is important in
      clinical trials, particularly in remote areas and minority groups. We describe a
      novel approach to improve adherence, retention and clinical review rates of
      Indigenous children. METHODS: This descriptive study was nested within a placebo
      controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3
      weeks. Indigenous children aged <=24-months hospitalised with acute bronchiolitis
      were recruited from two tertiary hospitals in northern Australia (Darwin and
      Townsville). Using mobile phones embedded within a culturally-sensitive approach
      and framework, we report our strategies used and results obtained. Our main
      outcome measure was rates of adherence to medications, retention in the RCT and
      self-presentation (with child) to clinic for a clinical review on day-21.
      RESULTS: Of 301 eligible children, 76 (21%) families declined participation and
      39 (13%) did not have access to a mobile phone. 186 Indigenous children were
      randomised and received dose one under supervision in hospital. Subsequently, 182
      (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180
      (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were
      needed to verify adherence. Importantly, over 97% of children remained in the RCT
      until their clinical endpoint at day-21. CONCLUSIONS: In our setting, the use of
      mobile phones within an Indigenous-appropriate framework has been an effective
      strategy to support a clinical trial involving Australian Indigenous children in
      urban and remote Australia. Further research is required to explore other
      applications of this approach, including the impact on clinical outcomes. TRIAL
      REGISTRATION: ACTRN12608000150347 (RCT component).

PMID- 24943962
TI  - Non-specific filtering of beta-distributed data.
AB  - BACKGROUND: Non-specific feature selection is a dimension reduction procedure
      performed prior to cluster analysis of high dimensional molecular data. Not all
      measured features are expected to show biological variation, so only the most
      varying are selected for analysis. In DNA methylation studies, DNA methylation is
      measured as a proportion, bounded between 0 and 1, with variance a function of
      the mean. Filtering on standard deviation biases the selection of probes to those
      with mean values near 0.5. We explore the effect this has on clustering, and
      develop alternate filter methods that utilize a variance stabilizing
      transformation for Beta distributed data and do not share this bias. RESULTS: We
      compared results for 11 different non-specific filters on eight Infinium
      HumanMethylation data sets, selected to span a variety of biological conditions.
      We found that for data sets having a small fraction of samples showing abnormal
      methylation of a subset of normally unmethylated CpGs, a characteristic of the
      CpG island methylator phenotype in cancer, a novel filter statistic that utilized
      a variance-stabilizing transformation for Beta distributed data outperformed the
      common filter of using standard deviation of the DNA methylation proportion, or
      its log-transformed M-value, in its ability to detect the cancer subtype in a
      cluster analysis. However, the standard deviation filter always performed among
      the best for distinguishing subgroups of normal tissue. The novel filter and
      standard deviation filter tended to favour features in different genome contexts;
      for the same data set, the novel filter always selected more features from CpG
      island promoters and the standard deviation filter always selected more features
      from non-CpG island intergenic regions. Interestingly, despite selecting largely
      non-overlapping sets of features, the two filters did find sample subsets that
      overlapped for some real data sets. CONCLUSIONS: We found two different filter
      statistics that tended to prioritize features with different characteristics,
      each performed well for identifying clusters of cancer and non-cancer tissue, and
      identifying a cancer CpG island hypermethylation phenotype. Since cluster
      analysis is for discovery, we would suggest trying both filters on any new data
      sets, evaluating the overlap of features selected and clusters discovered.

PMID- 24943964
TI  - The association of new inflammatory markers with type 2 diabetes mellitus and
      macrovascular complications: a preliminary study.
AB  - AIM: Type 2 diabetes mellitus (T2DM) is not simply a disease of hyperglycemia,
      but also is an inflammatory disorder. This study aimed to observe the expression
      of inflammation-related factors in elderly T2DM patients with or without
      macrovascular disease (MVD). PATIENTS AND METHODS: A total of 64 T2DM patients
      participated in this study, including 31 patients with MVD (group A) and 33
      patients without MVD (group B); and 30 healthy volunteers were recruited as
      normal control (group C). The levels of serum irisin, retinol-binding protein 4
      (RBP4) and adiponectin expression were all detected and compared between groups.
      RESULTS: The demographic and clinical characteristics were comparable between
      T2DM patients and healthy volunteers. For patients in group A, the serum levels
      of irisin, RBP4 and adiponectin were 12.05 +/- 2.12 pg/mL, 2.13 +/- 0.83 ug/mL
      and 45.65+/-20.13 ng/mL, respectively. While the corresponding parameters were
      26.11 +/- 4.09 pg/ml, 1.54 +/- 0.54 ug/ml and 57.93 +/- 23.47 ng/mL for patients
      in group B; and were 40.25 +/- 2.73 pg/mL, 0.98 +/- 0.36 ug/mL and 60.03 +/-
      20.26 ng/mL for healthy volunteers in group C, respectively. As compared to
      healthy volunteers, the levels of irisin, RBP4 and adiponectin were all
      significantly changed in T2DM patients; and the difference in irisin, RBP4 and
      adiponectin between T2DM patients with and without MVD were all significant (p =
      0.000, p = 0.001, and p = 0.029, respectively). Multivariate regression analysis
      showed that irisin and RBP4 are both independent predictors for MVD in T2DM
      patients. CONCLUSIONS: Inflammatory disorder is significantly in T2DM patients
      with MVD, and serum irisin and RBP4 would be reasonable new markers of MVD.

PMID- 24943963
TI  - Promoting microtubule assembly: A hypothesis for the functional significance of
      the +TIP network.
AB  - Regulation of microtubule (MT) dynamics is essential for many cellular processes,
      but the machinery that controls MT dynamics remains poorly understood. MT plus
      end tracking proteins (+TIPs) are a set of MT-associated proteins that
      dynamically track growing MT ends and are uniquely positioned to govern MT
      dynamics. +TIPs associate with each other in a complex array of inter- and intra
      molecular interactions known as the "+TIP network." Why do so many +TIPs bind to
      other +TIPs? Typical answers include the ideas that these interactions localize
      proteins where they are needed, deliver proteins to the cortex, and/or create
      regulatory pathways. We propose an additional and more mechanistic hypothesis:
      that +TIPs bind each other to create a superstructure that promotes MT assembly
      by constraining the structural fluctuations of the MT tip, thus acting as a
      polymerization chaperone. 

PMID- 24943965
TI  - Aminoguanidine protects against apoptosis of retinal ganglion cells in Zucker
      diabetic fatty rats.
AB  - AIM: The inhibition of advanced glycation end products (AGEs) and the receptor
      for AGEs (RAGE) mediated downstream signaling pathways have been suggested to
      have retinoprotective actions in diabetic retinopathy. Herein, we examined the
      protective effects of aminoguanidine (AG), an AGEs inhibitor, on diabetes-induced
      injury of retinal ganglion cells in the Zucker diabetic fatty (ZDF) rats.
      MATERIALS AND METHODS: Seven-week-old male ZDF rats were treated with AG (50
      mg/kg body weight) once a day orally for 13 weeks. Serum and vitreous
      concentration of AGEs were examined. Expressions of AGEs and its receptor (RAGE)
      were assessed by immunohistochemistry. Southwestern histochemistry was used to
      detect activated nuclear factor (NF)-kappaB. RESULTS: At the end of the study,
      vitreal levels of AGEs were significantly reduced in ZDF rats treated with AG.
      Similary, immunohistochemical analysis showed that AG significantly reduced the
      positive areas for AGEs and RAGE. Furthermore, AG strongly inhibited the loss of
      retinal ganglion cells by apoptosis. AG also suppressed the activation of to NF
      kappaB. CONCLUSIONS: Our results suggest that AG has retinoprotective properties
      through not only direct inhibition of AGEs formation but also downregulation of
      NF-kappaB.

PMID- 24943966
TI  - Parenteral nutrition in patients with inborn errors of metabolism - a therapeutic
      problem.
AB  - BACKGROUND: Parenteral nutrition is now a standard part of supportive treatment
      in pediatric departments. We describe four cases in which parenteral nutrition
      was extremely difficult due to coincidence with inborn errors of metabolism. The
      first two cases was fatty acid beta-oxidation disorders associated with
      necrotizing enterocolitis and congenital heart disease. Thus, limitations of
      intravenous lipid intake made it difficult to maintain a good nutritional status.
      The third case was phenylketonuria associated with a facial region tumour
      (rhabdomyosarcoma), in which parenteral nutrition was complicated because of a
      high phenylalanine content in the amino acid formulas for parenteral nutrition.
      The fourth patient was a child with late-diagnosed tyrosinemia type 1,
      complicated with encephalopathy - during intensive care treatment the patient
      needed nutritional support, including parenteral nutrition - we observed amino
      acid formula problems similar to those in the phenylketonuria patient. Parenteral
      nutrition in children with inborn errors of metabolism is a rare, but very
      important therapeutic problem. Total parenteral nutrition formulas are not
      prepared for this group of diseases.

PMID- 24943967
TI  - High sensitive CRP and pentraxine 3 as noninvasive biomarkers of nonalcoholic
      fatty liver disease.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has become the most common
      hepatic disease. Liver biopsy is the gold standard for the diagnosis of NAFLD. To
      overcome the problems with liver biopsy many studies are being performed to find
      noninvasive methods for the evaluation of hepatic status. AIM: This study aims to
      study to role of high sensitive CRP and pentraxine 3 in the setting of NAFLD.
      PATIENTS AND METHODS: thirty two NAFLD cases and 34 controls were enrolled. All
      subjects were studied clinically and blood was drawn for para-clinical studies.
      Liver biopsy was performed for all cases. Levels of hs-CRP and pentraxine were
      analyzed to find any significant difference for the stages of steatosis and
      fibrosis based on pathologic findings. RESULTS: Hs-CRP level was higher in
      nonalcoholic steatohepatitis (NASH) cases versus non-NASH cases. Its level was
      also increased in higher levels of fibrosis. Pentraxine 3 had no efficacy in
      differentiating different levels of NAFLD and fibrosis. CONCLUSIONS: Hs-CRP can
      be used in combination with other biomarkers in the noninvasive evaluation of
      NAFLD.

PMID- 24943968
TI  - Goblet cells carcinoid with mucinous adenocarcinoma of the vermiform appendix: a
      step towards the unitary intestinal stem cell theory?
AB  - Associations of various histotypes in appendiceal neoplasms may help elucidate
      the histogenesis of such uncommon tumors. We present the fourth published case of
      Goblet Cell Carcinoid (GCC) associated with mucinous adenocarcinoma of the
      appendix. This association has been described only for GCC and not for classic
      appendix carcinoids which are thought to originate from neuroendocrine-committed
      cells. The GCC-mucinous association adds more towards the theory of a pluripotent
      intestinal stem cell with amphicrine possibilities of differentiation. 

PMID- 24943969
TI  - siRNA-directed clusterin silencing promotes cisplatin antitumor activity in human
      non-small cell lung cancer xenografts in immunodeficient mice.
AB  - OBJECTIVES: In a previous analysis using a lung cancer cell lines model, we have
      found that therapies directed against sCLU and its downstream signaling targets
      pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin
      (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed
      against sCLU on the DDP-based chemotherapy in vivo, and explored the mechanism.
      MATERIALS AND METHODS: Using lung cancer cell lines, A549 cells and DDP-resistant
      A549 cells (A549DDP), we determined the effect of sCLU silencing using short
      interfering double-stranded RNA (siRNA) on chemosensitivity in immunocompromised
      mice bearing A549DDP tumors. We then determined the effect of sCLU overexpression
      via stable sCLU transfection on chemosensitivity in immunocompromised mice
      bearing A549 tumors. The effect of sCLU silencing or overexpression on pAkt and
      pERK1/2 expression and chemosensitivity in vivo was detected by western blot
      assay. RESULTS: The results showed sCLU silencing increased the chemosensitivity
      of A549DDP cells to DDP in vivo via downregulation of pAkt and pERK1/2
      expression. And sCLU overexpression decreased the chemosensitivity of A549 cells
      to DDP in vivo via upregulation of pAkt and pERK1/2 expression. CONCLUSIONS: DDP
      induced sCLU activation, which involved induction of pAkt and pERK1/2 activation
      that confer DDP resistance in immunocompromised mice. Alteration of this balance
      allows sensitisation to the antitumor activity of cisplatin chemotherapy.

PMID- 24943971
TI  - Effects of parathyroid hormone-related protein on osteogenic and adipogenic
      differentiation of human mesenchymal stem cells.
AB  - OBJECTIVE: This work aims to investigate the effects of parathyroid hormone
      related peptide (PTHrP) (1-86) on osteogenic and adipogenic differentiation of
      human mesenchymal stem cells (hMSCs) and the related mechanisms. MATERIALS AND
      METHODS: hMSCs were isolated and cultured in vitro. They were divided into
      control group, osteogenesis group, adipogenesis group, osteogenesis+PTHrP group
      and adipogenesis+PTHrP group. The cell proliferation and differentiation, and
      expression levels of osteopontin (OPN) and lipoprotein lipase (LPL) mRNA were
      observed. RESULTS: The proliferation rates of hMSCs in osteogenesis+PTHrP and
      adipogenesis+PTHrP group were significantly higher than that in control group,
      respectively (p < 0.01). The alkaline phosphatase (ALP)-positive osteoblasts
      firstly appeared in osteogenesis+PTHrP group, and Sudan IV-positive adipocytes
      firstly appeared in adipogenesis group. The expression level of OPN mRNA in
      osteogenesis+PTHrP group was significantly higher than that in osteogenesis group
      (p < 0.05), and that in adipogenesis+PTHrP group was also higher than
      adipogenesis group (p < 0.05). The expression level of LPL mRNA in
      osteogenesis+PTHrP group was significantly lower than that in osteogenesis group,
      and that in adipogenesis+PTHrP group was also lower than adipogenesis group (p <
      0.05). CONCLUSIONS: The osteogenesis and adipogenesis are related to each other
      during the induced differentiation of hMSCs. PTHrP (1-86) can promote the
      osteogenic differentiation and inhibits the adipogenic differentiation for hMSCs.

PMID- 24943970
TI  - The relationship between anticancer effect of metformin and the transcriptional
      regulation of certain genes (CHOP, CAV-1, HO-1, SGK-1 and Par-4) on MCF-7 cell
      line.
AB  - BACKGROUND: 1,1-dimethylbiguanide hydrochloride (biguanide metformin) is a
      hypoglycemic agent that is widely used in the treatment of Type 2 diabetes. Use
      of metformin was found to be associated with the lower risk of cancer. It is
      suggested that metformin has an anticancer and antiproliferative effect and
      affects the apoptosis by activating the AMPK and inhibiting the mammalian target
      of rapamycin (mTOR). Although the effects of metformin treatment of various types
      of cancers are defined with many mechanisms, the literature provides only
      sufficient information about how it affects the SGK-1, Par-4 and Cav-1 mRNA
      expressions and the impact of this effect on cytotoxicity. The breast cancer is
      globally one of the most important causes of cancer-related mortality for women.
      We, therefore investigated the possible effects of metmorfin on proliferation,
      cytotoxicity and some unfolded protein response (UPR) genes in the breast cancer
      cells (MCF-7). MATERIALS AND METHODS: We administrated 0.31 mM, 2.5 mM and 10 mM
      of metformin alone and in combination with 2-DG to the MCF-7 cells and monitored
      the cell viability and proliferation with real-time cell analyzer system for 48
      hours. We also measured CHOP, Cav-1, HO-1, SGK-1 and Par-4 genes mRNA expression
      levels using Real Time-Polymerase Chain Reaction (RT-PCR). We considered the
      GAPDH gene as reference gene and the control groups as calibrator. We performed
      an analysis for relative gene expressions of the study groups. RESULTS: Metformin
      caused transcriptional regulation of UPR and tumor-related genes in MCF-7 cells
      and inhibited the proliferation depending on the dose, resulting in cytotoxic
      effect. CONCLUSIONS: We consider that administration of metformin with
      chemotherapeutic agents could be an effective method in treatment of breast
      cancer through mechanisms such as reduced resistance to chemotherapy and
      increased cytotoxic activity.

PMID- 24943972
TI  - Expressing osteogenic growth peptide in the rabbit bone mesenchymal stem cells
      increased alkaline phosphatase activity and enhanced the collagen accumulation.
AB  - OBJECTIVES: The multipotent mesenchymal stem cells (MSCs) were distributed in the
      bone marrow stroma, and could generate all of the different skeletal cell
      lineages. The osteogenic differentiation of MSCs, which is indicated by the
      increased alkaline phosphatase (ALP) activity and the enhanced accumulation of
      collagen, could be induced by a tetradecapeptide termed osteogenic growth peptide
      (OGP). It has been hypothesized that the OGP induces the osteogenic
      differentiation of MSCs probably through regulating the fibroblast growth factor
      signaling pathways. Although the chemically synthesized OGP was widely applied to
      study the osteogenic differentiation of MSCs, transferring and expressing OGP
      gene in target cells is more desirable, especially for gene therapy, given the
      advantages and convenience on the stable expression of OGP. MATERIALS AND
      METHODS: In this study, we attempt to test the effect of OGP gene transfection;
      we constructed a eukaryotic expression vector, pcDNA3.1-OGP, which contained the
      OGP-coding DNA fragment. Subsequently, the vector was transfected into the rabbit
      MSCs. RESULTS: A significant increase of ALP activity was detected in the
      supernatant of pcDNA3.1-OGP transfected MSCs, and the enhanced collagen
      accumulation, which was inferred by the increased hydroxyproline content and RT
      PCR. CONCLUSIONS: These results implied that transfecting the OGP-expressing
      vectors into MSCs might induce the osteogenic differentiation of MSCs.

PMID- 24943973
TI  - Lycopene protects bone marrow mesenchymal stem cells against ischemia-induced
      apoptosis in vitro.
AB  - OBJECTIVE: Bone marrow mesenchymal stem cells (MSCs) have been identified to have
      the potential to differentiate into multiple types of cells. And the therapy
      based on transplantation of MSCs in some solid organs has been suggested in
      recent years. However, the rejection reaction often occurs in the transplantation
      of MSCs and could induce cell death. Ischemia has been reported to one of the
      main causes of MSCs death during transplantation. The primary objective of this
      study was to verify whether a natural antioxidant, lycopene, could protect MSCs
      from ischemia-induced apoptosis in vitro. MATERIALS AND METHODS: MSCs were
      isolated from bone marrow in mice femoral bone marrow. The effect of lycopene on
      MSCs during oxygen-glucose-serum deprivation was investigated. RESULTS: We found
      that lycopene protected MSCs from serum deprivation- and hypoxia-induced
      apoptosis. The reactive oxygen species (ROS) generation and inducible nitric
      oxide synthetase expression were also inhibited dose-dependently by lycopene.
      Further investigation revealed that lycopene could activate phosphoinositide-3
      kinase (PI3K)/Akt. Pretreatment with PI3K/Akt inhibitors prevented the protective
      effect of lycopene on MSCs. CONCLUSIONS: Lycopene could protect MSCs from
      ischemia-induced apoptosis through reducing ROS generation; therefore, lycopene
      could be useful in MSC transplantation.

PMID- 24943974
TI  - Neuropsychological and neurophysiological evaluation of cognitive deficits
      related to the severity of traumatic brain injury.
AB  - OBJECTIVES: Cognitive impairment is a common permanent sequela of traumatic brain
      injury (TBI). Its objectivization is based on neuropsychological and
      neurophysiological assessment. Neuropsychological evaluation requires a test
      battery, whereas for neurophysiological assessment the most significant is
      application of P300 Event-Related Potentials (ERPs). The aim of the study was to
      determine whether it is possible to differentiate between degrees of severity of
      TBI on the basis of neuropsychological and neurophysiological parameters.
      PATIENTS AND METHODS: A total of 90 patients with closed TBI were evaluated at
      least one year after trauma. Subjects were classified into three groups according
      to severity of TBI: mild, moderate and severe. In all subjects the Intelligence
      Test, the Wisconsin Card Sorting Test (WCST) and P300 ERPs were performed.
      RESULTS: General intelligence measures did not prove sensitivity enough to
      differentiate levels of severity of TBI, whereas the number of achieved
      categories on the WCST significantly discerned patients with mild and moderate
      TBI from patients with severe TBI. Perseverative errors significantly separated
      patients with mild TBI from patients with moderate and severe TBI. Non
      perseverative errors significantly differentiated only patients with mild TBI
      from patients with severe TBI. Finally, P300 latency (EPLAT) significantly
      differentiated patients with mild TBI from patients with moderate and severe TBI.
      The results show that the applied test battery can discriminate between different
      levels of severity of TBI and emphasize the importance of P300 ERP in the
      evaluation of patients with brain injury. CONCLUSIONS: Our findings indicate that
      the WCST and ERP P300 latency have a significant role in the assessment of
      cognitive deficit related to TBI.

PMID- 24943975
TI  - Neurobehavioral studies, in transgenic F3/CONTACTIN (C57BL/6J * CBA) mice, on
      cognitive and anxiety aspects during late-adolescential period.
AB  - OBJECTIVE: Besides than in the control of developmental events, axonal adhesive
      glycoproteins may be also involved in functions requiring fine organization and
      connectivity of the nervous tissue. We previously demonstrated morphological
      alterations and functional cerebellar deficits in transgenic mice (TAG/F3 mice)
      ectopically expressing the F3/Contactin axonal glycoprotein under the control of
      a selected regulatory region from the Transient Axonal Glycoprotein (TAG-1) gene.
      In the present study, the hippocampal function was explored by evaluating the
      ability of TAG/F3 mice to encode spatial and non-spatial relationships between
      discrete stimuli and to analyze an anxiety-related behavior. MATERIALS AND
      METHODS: To the first end, mice were placed in an "open-Field" containing five
      objects and, after three sessions of habituation (S2-S4), their reactivity to
      objects displacement (S5-S4) and object substitution (S7-S6) was examined.To the
      second end, mice were placed in the "elevated zero maze", a standard test to
      explore the anxiety-related behavior, in order to study, in transgenic mice, the
      effects of F3 misexpression on emotional reactivity by measuring the avoidance of
      the unsheltered open sectors. RESULTS: Statistical evaluations of reactivity to
      object novelty, TAG-F3 mice showed a lower DO exploration with respect to wild
      type mice and, regarding DOs, TAG/F3 mice interacted less than wild-type mice,
      showing an impaired spatial change response. Furthermore, the number of HDIPS in
      transgenic TAG/F3 mice resulted significantly lower with respect to the controls
      (wild type). CONCLUSIONS: These results indicate that the coordinated expression
      of axonal adhesive glycoproteins may be relevant for the functional maturation of
      the hippocampus.

PMID- 24943976
TI  - A simple and cheap system to speed up and to control the tumescent technique
      procedure: the Tedde's system.
AB  - We have devised a low cost system to quickly infiltrate tumescent solution: we
      call it the "Tedde's system". This low-cost system offers an improvement in
      quality and quantity of the infiltration because all the procedure depends on the
      operators, reducing also the time of the infiltration and consequently of the
      whole surgical procedure. Moreover, this system can be applied to other surgical
      procedure that requires large infiltration volumes. 

PMID- 24943977
TI  - Are pharmacological properties of anticoagulants reflected in pharmaceutical
      pricing and reimbursement policy? Out-patient treatment of venous thromboembolism
      and utilization of anticoagulants in Poland.
AB  - OBJECTIVES: Pharmacotherapy with vitamin K antagonists (VKA) and low-molecular
      weight heparins (LMWH) is a major cost driver in the treatment of venous
      thromboembolism (VTE). Major representatives of anticoagulants in Europe include:
      acenocoumarol and warfarin (VKA), enoxaparin, dalteparin, nadroparin, reviparin,
      parnaparin and bemiparin (LMWH). Aim of this report is to measure and critically
      assess the utilization of anticoagulants and other resources used in the out
      patient treatment of VTE in Poland. To confront the findings with available
      scientific evidence on pharmacological and clinical properties of anticoagulants.
      MATERIALS AND METHODS: The perspectives of the National Health Fund (NHF) and the
      patients were adopted, descriptive statistics methods were used. The data were
      gathered at the NHF and the clinic specialized in treatment of coagulation
      disorders. RESULTS: Non-pharmacological costs of treatment were for the NHF 1.6
      times higher with VKA than with LMWH. Daily cost of pharmacotherapy with LMWH
      turned out higher than with VKA (234 times for the NHF, 42 times per patient).
      Within both LMWH and VKA the reimbursement due for the daily doses of a
      particular medication altered in the manner inversely proportional to the level
      of patient co-payment. Utilization of long-marketed and cheap VKA was dominated
      by LMWH, when assessed both through the monetary measures and by the actual
      volume of sales. Pharmaceutical reimbursement policy favored the more expensive
      equivalents among VKA and LMWH, whereas in the financial terms the patients were
      far better off when remaining on a more expensive alternative. CONCLUSIONS: The
      pharmaceutical pricing and reimbursement policy of the state should be more
      closely related to the pharmacological properties of anticoagulants.

PMID- 24943978
TI  - Treatment of uterine prolapse with bilateral hydronephrosis in a young
      nulliparous woman; a new minimally invasive extraperitoneal technique.
AB  - A 37-year-old nulligravid woman presented with a 2-year history of uterine
      prolapse along with mixed incontinence. Gynecological examination confirmed third
      degree cystocele and uterine prolapse. Renal ultrasonography showed enlarged
      kidneys and marked dilation of the bilateral pelvicalyceal system. She was
      hospitalized and a ring pessary was inserted after bladder catheterization. Her
      preoperative evaluation was performed and the patient was operated one month
      after her first admission. Anterior colporrhaphy along with Kurt Extraperitoneal
      Ligamentopexy was performed without any complication. A control visit on second
      postoperative month revealed recovery of incontinence symptoms and no prolapse
      was observed. To our knowledge this is the first reported treatment of a case
      with bilateral hydronephrosis due to uterine prolapse that were corrected and
      overcame with a novel minimally invasive extraperitoneal approach by fixation of
      bilateral round ligaments to the rectus fascia sheet. 

PMID- 24943979
TI  - The relationship between microalbuminuria and isolated coronary artery ectasia.
AB  - AIM: Coronary artery ectasia (CAE), is at least 1.5 fold dilatation of at least
      one coronary segment due to congenital or acquired causes. In this study, we aim
      to investigate the relation of CAE with microalbuminuria, which is a marker of
      endothelial dysfunction shown to be associated with increased cardiovascular
      mortality and morbidity. PATIENTS AND METHODS: Patients with CAE detected during
      routine coronary angiogram (CAG) and individuals with normal CAG findings have
      been included in our study. Urine albumin levels were measured by
      immunoturbidimetric method from samples collected in the morning. Patients with
      an albumin/creatinine (A/C) ratio less than 0.03 were normal and the ones between
      values 0.03-0.3 were considered to be microalbuminuric. Patients whose A/C ratios
      > 0.3 had macroalbuminuria and were excluded. RESULTS: A total of 105 patients
      (60 with CAE and 45 with normal CAG) were included in the study. Serum
      creatinine, low-density lipoprotein cholesterol and homocysteine levels were
      increased in the CAE group. Urine A/C ratio was 0.036 +/- 0.040 in the CAE group
      and 0.018 +/- 0.013 in the controls; the difference was statistically significant
      (p = 0.002). CONCLUSIONS: Blood homocysteine levels and urinary albumin levels
      are significantly increased in patients with CAE when compared to individuals
      with normal CAG. Microalbuminuria and hyperhomocysteinemia, two markers of
      endothelial dysfunction might be associated with pathophysiologic processes
      leading to CAE.

PMID- 24943980
TI  - Effects of metoprolol and small intestine RNA on marrow-derived endothelial
      progenitor cells applied for autograft transplantation in heart disease.
AB  - AIMS: The objective of this project was to improve the effect of EPC autograft
      transplantation and observe the tolerance of EPCs to I/R injury affected by
      metoprolol and small intestine RNA. MATERIALS AND METHODS: We isolated bone
      marrow-derived EPCs and examined the effects of metoprolol and small intestine
      RNA on EPCs to ischemia at different time points after reperfusion. EPCs growth
      curve, secretion, apoptosis and mortality were also analyzed. RESULTS: EPCs will
      be better protected if the blood can be recovered within 4 hours after ischemia
      for cardiac muscle cells and pretreatment of EPCs with metoprolol or small
      intestine RNA could protect and promote EPCs proliferation. CONCLUSIONS: Our
      study demonstated that pretreatment of EPCs with metoprolol or small intestine
      RNA will increase the EPCs proliferation and may improve the EPCs autograft
      transplantation ability.

PMID- 24943981
TI  - Two cases of very late bare-metal stent thrombosis and literature review.
AB  - BACKGROUND: Bare metal stents (BMS) are commonly used in the treatment of
      coronary artery disease. Very late stent thrombosis (VLST) is a quite rare
      clinical entity. However, it is a serious complication that often results
      myocardial infarction or death. Since the stent endothelialization is considered
      to be completed within 4 weeks after the intervention, VLST is not common with
      BMS. PATIENTS AND METHODS: The pathogenesis of the VLST is poorly defined.
      Herein, we report two cases of VLST in which one a 62 year old male patient
      devoloped VLST of a BMS implanted in the right coronary artery (RCA) and
      presented inferior myocardial infarction and other a 48 year old male patient
      devoloped very late thrombosis of a BMS implanted in the RCA and presented
      inferior myocardial infarction, respectively. CONCLUSIONS: On the basis of these
      two cases and our review of the current literature we suggest that what can be
      done to prevent this rare but offending complication. Moreover, in the light of
      new imaging modalities such as optical coherence tomography (OCT), the
      pathophysiology of stent thrombosis will be clearly defined and preventive
      measures will be taken before it occurs.

PMID- 24943983
TI  - Could monitoring normotensives delay progression to hypertension?

PMID- 24943982
TI  - Could monitoring normotensives delay progression to hypertension?

PMID- 24943984
TI  - Coronary artery anomaly: what does not fit the patient or the interpretation?

PMID- 24943985
TI  - Importance of epicardial adipose tissue thickness in obese adolescents.

PMID- 24943986
TI  - PHYTOALEXIN DEFICIENT 4 affects reactive oxygen species metabolism, cell wall and
      wood properties in hybrid aspen (Populus tremula L. * tremuloides).
AB  - The phytoalexin deficient 4 (PAD4) gene in Arabidopsis thaliana (AtPAD4) is
      involved in the regulation of plant--pathogen interactions. The role of PAD4 in
      woody plants is not known; therefore, we characterized its function in hybrid
      aspen and its role in reactive oxygen species (ROS)-dependent signalling and wood
      development. Three independent transgenic lines with different suppression levels
      of poplar PAD expression were generated. All these lines displayed deregulated
      ROS metabolism, which was manifested by an increased H2O2 level in the leaves and
      shoots, and higher activities of manganese superoxide dismutase (MnSOD) and
      catalase (CAT) in the leaves in comparison to the wild-type plants. However, no
      changes in non-photochemical quenching (NPQ) between the transgenic lines and
      wild type were observed in the leaves. Moreover, changes in the ROS metabolism in
      the pad4 transgenic lines positively correlated with wood formation. A higher
      rate of cell division, decreased tracheid average size and numbers, and increased
      cell wall thickness were observed. The results presented here suggest that the
      Populus tremula * tremuloides PAD gene might be involved in the regulation of
      cellular ROS homeostasis and in the cell division--cell death balance that is
      associated with wood development.

PMID- 24943987
TI  - A multifaceted pharmacist intervention to improve antihypertensive adherence: a
      cluster-randomized, controlled trial (HAPPy trial).
AB  - WHAT IS KNOWN AND OBJECTIVES: About half of all patients taking antihypertensives
      discontinue treatment by 12 months. There is potential for substantial health
      gains at both individual and population levels through improved treatment
      adherence. The objective was to evaluate a community pharmacist intervention to
      improve adherence with antihypertensive medicines with a view to improving blood
      pressure (BP) control. METHODS:  DESIGN: prospective, non-blinded, cluster
      randomized, controlled trial. PARTICIPANTS: adults with primary hypertension who
      obtained antihypertensives in the previous 6 months. Patients with poor refill
      adherence were preferentially identified with the help of a purpose-built
      software application. INTERVENTION: package comprising BP monitor; training on BP
      self-monitoring; motivational interviewing; medication use review; prescription
      refill reminders. FOLLOW-UP: six months. PRIMARY OUTCOME: change in proportion
      self-reporting medication adherence. Secondary outcome: BP changes. RESULTS:
      Participants (n = 395; intervention - 207; control - 188) had a mean age of 66.7
      years; 51.1% were males. The proportion of adherent participants increased in
      both groups but was not significantly different between groups [57.2% to 63.6%
      (control) vs. 60.0% to 73.5% (intervention), P = 0.23]. The mean reduction in
      systolic BP was significantly greater in the intervention group (10.0 mmHg vs.
      4.6 mmHg; P = 0.05). The proportion of patients who were non-adherent at baseline
      and adherent at 6 months was 22.6% (95%CI 5.1-40.0%) higher in the intervention
      group (61.8% vs. 39.2%, P = 0.007). Among participants with baseline BP above
      target, reduction of systolic BP was significantly greater in the intervention
      group [by 7.2 mmHg (95%CI 1.6-12.8 mmHg); (P = 0.01)]. Among participants non
      adherent at baseline and above target BP, the proportion reporting adherence at 6
      months was significantly greater in the intervention group [56.8% vs. 35.9%, P =
      0.039). WHAT IS NEW AND CONCLUSION: This community pharmacist intervention
      resulted in improved adherence to antihypertensive medication and reduced
      systolic BP.

PMID- 24943988
TI  - Pharmacokinetic studies and LC-MS/MS method development of ganciclovir and
      dipeptide monoester prodrugs in Sprague Dawley rats.
AB  - Ganciclovir (GCV) is utilized as an anti-herpetic agent. Reports from our
      laboratory have suggested that dipeptide ester prodrugs of GCV exhibit high
      affinity towards the oligopeptide transporter hPEPT1 and therefore seem to be
      promising candidates for the treatment of oral herpes virus infections. In this
      study, we have examined the bio-availability of a dipeptide prodrug of GCV after
      oral administration in jugular cannulated Sprague-Dawley rats. A new bio
      analytical method was developed with Q-TRAP liquid chromatography tandem mass
      spectroscopy (LC-MS/MS) for simultaneous analysis of GCV, Valine-GCV (VGCV) and
      Tyrosine-Valine-GCV (YVGCV). Acyclovir (ACV) was used as an internal standard in
      the analysis. Area under plasma-concentration time curves for total concentration
      of GCV after oral administration of YVGCV was found to be approximately 200 %
      more than that of GCV following intestinal absorption. A complete conversion of
      the dipeptide prodrug (YVGCV) to parent compound, GCV, by hepatic first-pass
      metabolism was evident due to the absence of intermediate metabolite VGCV and
      administered prodrug YVGCV. The dipeptide prodrugs of GCV exhibit higher systemic
      availability of regenerated GCV upon oral administration and thus seem to be
      promising drug candidate in the treatment of systemic herpes infections.

PMID- 24943990
TI  - Citrullination of epithelial neutrophil-activating peptide 78/CXCL5 results in
      conversion from a non-monocyte-recruiting chemokine to a monocyte-recruiting
      chemokine.
AB  - OBJECTIVE: To examine whether the citrullinated chemokines epithelial neutrophil
      activating peptide 78 (ENA-78)/CXCL5, macrophage inflammatory protein
      1alpha/CCL3, and monocyte chemotactic protein 1/CCL2 are detected in the biologic
      fluid of patients with rheumatoid arthritis (RA), and if so, to determine the
      biologic activities of these chemokines. METHODS: Recombinant human chemokines
      were citrullinated by peptidylarginine deiminase. Enzyme-linked immunosorbent
      assays were performed to measure the concentrations of citrullinated chemokines
      in sera from patients with rheumatoid arthritis (RA) and normal individuals and
      in synovial fluid from patients with RA, patients with osteoarthritis (OA), and
      patients with other inflammatory rheumatic diseases. The correlation between the
      citrullinated chemokine levels and clinical data was analyzed. Monocyte and
      neutrophil chemotaxis assays were performed, and native (noncitrullinated) or
      citrullinated ENA-78/CXCL5 was injected into mouse knees to evaluate the biologic
      activities of these chemokines. RESULTS: The concentration of citrullinated ENA
      78/CXCL5 was significantly higher in RA sera and SF than in normal sera and in SF
      from patients with other rheumatic diseases including OA. In RA SF, a strong
      correlation between the amount of citrullinated ENA-78/CXCL5 and the C-reactive
      protein level or the erythrocyte sedimentation rate was observed. Citrullinated
      ENA-78/CXCL5 induced monocyte chemotaxis via CXCR1 and CXCR2, while
      noncitrullinated ENA-78/CXCL5 did not. In a mouse model of inflammatory
      arthritis, citrullinated ENA-78/CXCL5 induced more severe inflammation and
      recruited more monocytes than did noncitrullinated ENA-78/CXCL5. CONCLUSION:
      Citrullinated ENA-78/CXCL5 is highly correlated with RA disease activity and,
      unlike noncitrullinated ENA-78/CXCL5, recruits monocytes. These results indicate
      that citrullinated ENA-78/CXCL5 may exert previously unrecognized inflammatory
      properties in RA by recruiting monocytes to inflamed joint tissue.

PMID- 24943989
TI  - Pyroglutamate-amyloid-beta and glutaminyl cyclase are colocalized with amyloid
      beta in secretory vesicles and undergo activity-dependent, regulated secretion.
AB  - BACKGROUND AND AIMS: N-truncated pyroglutamate (pGlu)-amyloid-beta [Abeta(3
      40/42)] peptides are key components that promote Abeta peptide accumulation,
      leading to neurodegeneration and memory loss in Alzheimer's disease. Because
      Abeta deposition in the brain occurs in an activity-dependent manner, it is
      important to define the subcellular organelle for pGlu-Abeta(3-40/42) production
      by glutaminyl cyclase (QC) and their colocalization with full-length Abeta(1
      40/42) peptides for activity-dependent, regulated secretion. Therefore, the
      objective of this study was to investigate the hypothesis that pGlu-Abeta and QC
      are colocalized with Abeta in dense-core secretory vesicles (DCSV) for activity
      dependent secretion with neurotransmitters. METHODS: Purified DCSV were assessed
      for pGlu-Abeta(3-40/42), Abeta(1-40/42), QC, and neurotransmitter secretion.
      Neuron-like chromaffin cells were analyzed for cosecretion of pGlu-Abeta, QC,
      Abeta, and neuropeptides. The cells were treated with a QC inhibitor, and pGlu
      Abeta production was measured. Human neuroblastoma cells were also examined for
      pGlu-Abeta and QC secretion. RESULTS: Isolated DCSV contain pGlu-Abeta(3-40/42),
      QC, and Abeta(1-40/42) with neuropeptide and catecholamine neurotransmitters.
      Cellular pGlu-Abeta and QC undergo activity-dependent cosecretion with Abeta and
      enkephalin and galanin neurotransmitters. The QC inhibitor decreased the level of
      secreted pGlu-Abeta. The human neuroblastoma cells displayed regulated secretion
      of pGlu-Abeta that was colocalized with QC. CONCLUSIONS: pGlu-Abeta and QC are
      present with Abeta in DCSV and undergo activity-dependent, regulated cosecretion
      with neurotransmitters.

PMID- 24943991
TI  - Upregulation HOXA10 homeobox gene in endometrial cancer: role in cell cycle
      regulation.
AB  - Homeobox genes encode a group of transcription factors that regulate embryonic
      development, organ differentiation and cell proliferation. Some researchers found
      that homeobox gene family could regulate the expression of cell cycle-related
      factors which are involved in tumorigenesis. The aim of the present study was to
      determine whether HOXA10 gene could regulate the expression of p21 and control
      the cell cycle in endometrial cancer. Real-time PCR and Western blot were used to
      analyze HOXA10 and p21 gene expression in tissue samples of normal endometrium
      and endometrial cancer. Upregulate and downregulate HOXA10 gene in endometrial
      cancer cells by HOXA10-vector and HOXA10-siRNA, p21 mRNA and protein expression
      were tested by real-time PCR and Western blot. FCM analyze the cell cycle
      alteration, and cell count and EdU assay were recruited to detect cell
      proliferative activity after upregulation of HOXA10. Expression of HOXA10 and p21
      gene decreased in endometrial cancer, and the expression level of HOXA10 was
      correlated with cancer grade. The percentage of G1 phase cells increased, and
      cell proliferative activity decreased after upregulate HOXA10 expression. The
      expression of p16, p27, Myc, Cyclin D1, Cyclin E, CDK2, CDK4 and CDK6 did not
      alter after upregulation HOXA10. P21 gene mRNA and protein increased/decreased
      after upregulation/downregulation HOXA10 expression in cancer cells. HOXA10
      regulates G1 phase arrest in endometrial cancer which may be mediated by p21. 

PMID- 24943992
TI  - Overexpression of NUAK1 is associated with disease-free survival and overall
      survival in patients with gastric cancer.
AB  - Novel (nua) kinase family 1 (NUAK1) is a member of the human adenosine
      monophosphate-activated protein kinases family, which is overexpressed in
      multiple human malignancies and thought to be involved in tumor invasion and
      metastasis ability. Our study is to investigate the association of NUAK1
      expression with clinicopathological parameters and prognostic significance of
      patients with gastric cancer. The expression patterns of the NUAK1 protein in 117
      primary archival gastric cancer specimens and 46 adjacent normal epithelial
      tissues from patients were detected by immunohistochemistry assay. Staining
      evaluation results were analyzed statistically in relation to various
      clinicopathological characters, recurrence-free survival and overall survival.
      High level of NUAK1 expression was detected in gastric cancer, significantly more
      than in adjacent normal epithelial cells. In gastric cancer, NUAK1 was positively
      correlated with depth of invasion, lymph node metastasis, pathological stage,
      surgical resection and histological differentiation. However, no correlations
      between NUAK1 expression and patients' age, sex, tumor size, location, CA19-9 or
      CEA were detected. The recurrence-free survival and overall survival were
      significantly shorter for patients with NUAK1 higher scores than those with NUAK1
      lower scores. Multivariate analysis identified NUAK1 was an independent
      prognostic factor for both recurrence-free survival and overall survival. Our
      findings provided convincing evidence for NUAK1 overexpression, which was tightly
      associated with more aggressive tumor behavior and a poor prognosis, indicating
      that NUAK1 is a valuable molecular biomarker for gastric cancer progression. It
      might also act as a promising target for both prognostic prediction and
      therapeutics. 

PMID- 24943993
TI  - Relation of epicardial fat to central aortic pressure and left ventricular
      diastolic function in patients with known or suspected coronary artery disease.
AB  - The present study tested the hypothesis that epicardial fat may be associated
      with augmented central aortic pressure and impaired left ventricular (LV)
      function. We studied 134 consecutive patients undergoing left-sided cardiac
      catheterization for coronary artery disease (CAD) and examined the relation of
      epicardial fat volume measured by multi-detector computed tomography to ascending
      aortic pressure and LV ejection fraction determined by cardiac catheterization as
      well as indices of LV diastolic function assessed by Doppler echocardiography
      [early diastolic mitral annular velocity (e') and a ratio of early diastolic
      mitral inflow to annular velocities (E/e')]. Epicardial fat volume indexed to
      body surface area correlated positively with age (r = 0.24, P < 0.01), body mass
      index (r = 0.38, P < 0.001), systolic aortic pressure (r = 0.21, P < 0.05),
      aortic pulse pressure (r = 0.23, P < 0.01), LV ejection fraction (r = 0.22, P <
      0.05) and E/e' (r = 0.24, P < 0.05) and did negatively with e' (r = -0.31, P <
      0.05). In multivariate linear regression including potential confounders,
      increased epicardial fat volume index correlated with aortic systolic and pulse
      pressure and LV diastolic function indices, but not LV ejection fraction. In
      conclusion, we found that epicardial fat was associated with augmented central
      aortic pressure and LV diastolic dysfunction in patients with known or suspected
      CAD.

PMID- 24943994
TI  - The effect of fibers on coagulation of casein-based enteral nutrition in an
      artificial gastric digestion model.
AB  - A serious complication seen in critically ill patients is the solidification of
      enteral nutrition causing gastrointestinal obstruction. It has been suggested
      that enteral nutrition enriched with insoluble fibers may increase the risk of
      this complication. Therefore, we investigate the effect of soluble and insoluble
      dietary fibers on the coagulation of a casein-based enteral nutrition in an
      artificial gastric digestion model. A 100% casein-based enteral nutrition was
      enriched with increasing concentrations of soluble fibers (acacia fiber,
      oligofructose and inulin) and insoluble fibers (soy polysaccharide, resistant
      starch and alpha cellulose). After digestion in an artificial gastric model, the
      chyme was poured over sequentially placed sieves, separating the coagulate into
      size fractions of larger than 2 mm, between 1 and 2 mm, and between 0.25 and 1
      mm. Of these fractions we measured wet weight, dry weight and protein content. A
      significant effect on the fraction larger than 2 mm was considered to be
      clinically relevant. Addition of high concentrations soy polysaccharide and
      resistant starch to a casein-based enteral nutrition, did not alter the wet
      weight, whereas dry weight and protein content of the coagulate was significantly
      reduced. When high concentrations of soy polysaccharide and resistant starch are
      added to a 100% casein-based enteral nutrition, the coagulate consist of more
      water and less proteins, which may lead to an increased protein digestion and
      absorption in a clinical setting. The suggestion that insoluble fibers increase
      the risk of gastrointestinal obstruction in critically ill patients is not
      supported by these data. 

PMID- 24943995
TI  - Racial disparities in breast cancer: more bad news.

PMID- 24943996
TI  - Maintaining the potential of a psycho-educational program: efficacy of a booster
      session after an intervention offered family caregivers at disclosure of a
      relative's dementia diagnosis.
AB  - BACKGROUND: Booster sessions as a means of maintaining the benefits of psycho
      educational programs have received little attention in caregiving research.
      Caregivers were offered a booster session following participation in a program
      entitled Learning to Become a Family Caregiver (LBFC) intended to facilitate
      transition to the caregiver role after diagnostic disclosure of dementia in a
      relative. The 90-minute booster session served to review program content and
      afforded the opportunity to discuss and practice learned skills. This study
      sought to test the efficacy of the booster session in maintaining or recovering
      program effects at six months post-program. METHOD: Participants in the program
      were randomly assigned to a group that received the booster session (n = 31) or a
      group that did not (n = 29). A third control group was also formed, which
      continued to receive only the usual care provided in memory clinics. Eligible
      participants - French-speaking primary caregivers of a relative diagnosed with
      Alzheimer's in the past nine months - were recruited in memory clinics in Quebec
      (Canada). Participants were blindly assessed before randomization and six months
      after the booster session on outcomes associated with a healthy role transition.
      RESULTS: Prediction analyses revealed one significant positive effect of the
      booster session: emergence of preparedness to provide care. Moreover, with or
      without the booster session, the program continued to have a positive effect on
      psychological distress and contributed to the emergence of self-efficacy in
      dealing with caregiving situations. The booster session had no significant effect
      on knowledge of services, planning for future care needs, use of reframing as a
      coping strategy, perceived informal support, and family conflicts. CONCLUSION:
      The limited effect observed is discussed in terms of the booster session's
      content and intensity. Recommendations are made for designing future research on
      the effect of booster sessions, including the importance of including a placebo
      booster group.

PMID- 24943997
TI  - Suicidal ideation in adolescents: A structural equation modeling approach.
AB  - The purpose of this study is to test a model linking adolescents' experience of
      violence and peer support to their happiness and suicidal ideation. The
      participants were high school students in Seoul, and in Kyungi, and Chungnam
      Provinces in Korea. The Conflict Tactics Scale, School Violence Scale, Oxford
      Happiness Inventory, and Suicidal Ideation Questionnaire were administered to
      just over 1000 adolescents. The model was tested using a path analysis technique
      within structural equation modeling. The model fit indices suggest that the
      revised model is a better fit for the data than the original hypothesized model.
      The experience of violence had a significant negative direct effect and peer
      support had a significant positive direct effect on their happiness. Happiness
      had a significant negative effect and the experience of violence had a
      significant positive effect on suicidal ideation. These findings demonstrate the
      fundamental importance of reducing exposure of violence to adolescents, and that
      increasing peer support and their happiness may be the key to adolescent suicidal
      ideation prevention.

PMID- 24943998
TI  - The potential of neural stem cell transplantation for the treatment of fetal
      alcohol spectrum disorder.
AB  - Fetal alcohol spectrum disorder (FASD) is caused by intrauterine exposure to
      alcohol and can cause a full range of abnormalities to brain development, as well
      as long-term sequelae of cognitive, sensory and motor impairments. The incidence
      is estimated to be as high as 2% to 5% in children born within the US, however
      the prevalence is even higher in low socioeconomic populations. Despite the
      various mechanisms thought to explain the etiology of FASD, molecular targets of
      ethanol toxicity during development are not completely understood. More recent
      findings explore the role of GABA-A and GABA-B mechanisms, as well as cell death,
      cell signaling and gene expression malfunctions. Stem cell based therapies have
      grown exponentially over the last decade, which have lead to novel clinical
      interventions across many disciplines. Thus, early detailed understanding of the
      therapeutic potential of stem cell research has provided promising applications
      across a wide range of illnesses. Consequently, these potential benefits may
      ultimately lead to a reduced incidence and severity of this highly preventable
      and prevalent birth defect. It is recognized that stem cell derivations provide
      unique difficulties and limitations of therapeutic applications. This review will
      outline the current knowledge, along with the benefits and challenges of stem
      cell therapy for FASD. 

PMID- 24943999
TI  - Fiber-based wearable electronics: a review of materials, fabrication, devices,
      and applications.
AB  - Fiber-based structures are highly desirable for wearable electronics that are
      expected to be light-weight, long-lasting, flexible, and conformable. Many
      fibrous structures have been manufactured by well-established lost-effective
      textile processing technologies, normally at ambient conditions. The advancement
      of nanotechnology has made it feasible to build electronic devices directly on
      the surface or inside of single fibers, which have typical thickness of several
      to tens microns. However, imparting electronic functions to porous, highly
      deformable and three-dimensional fiber assemblies and maintaining them during
      wear represent great challenges from both views of fundamental understanding and
      practical implementation. This article attempts to critically review the current
      state-of-arts with respect to materials, fabrication techniques, and structural
      design of devices as well as applications of the fiber-based wearable electronic
      products. In addition, this review elaborates the performance requirements of the
      fiber-based wearable electronic products, especially regarding the correlation
      among materials, fiber/textile structures and electronic as well as mechanical
      functionalities of fiber-based electronic devices. Finally, discussions will be
      presented regarding to limitations of current materials, fabrication techniques,
      devices concerning manufacturability and performance as well as scientific
      understanding that must be improved prior to their wide adoption. 

PMID- 24944000
TI  - Sensitivity of ecological soil-screening levels for metals to exposure model
      parameterization and toxicity reference values.
AB  - Ecological soil-screening levels (Eco-SSLs) were developed by the United States
      Environmental Protection Agency (USEPA) for the purposes of setting conservative
      soil screening values that can be used to eliminate the need for further
      ecological assessment for specific analytes at a given site. Ecological soil
      screening levels for wildlife represent a simplified dietary exposure model
      solved in terms of soil concentrations to produce exposure equal to a no-observed
      adverse-effect toxicity reference value (TRV). Sensitivity analyses were
      performed for 6 avian and mammalian model species, and 16 metals/metalloids for
      which Eco-SSLs have been developed. The relative influence of model parameters
      was expressed as the absolute value of the range of variation observed in the
      resulting soil concentration when exposure is equal to the TRV. Rank analysis of
      variance was used to identify parameters with greatest influence on model output.
      For both birds and mammals, soil ingestion displayed the broadest overall range
      (variability), although TRVs consistently had the greatest influence on
      calculated soil concentrations; bioavailability in food was consistently the
      least influential parameter, although an important site-specific variable.
      Relative importance of parameters differed by trophic group. Soil ingestion
      ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different
      patterns were exhibited, depending on which parameter, trophic group, and analyte
      combination was considered. The approach for TRV selection was also examined in
      detail, with Cu as the representative analyte. The underlying assumption that
      generic body-weight-normalized TRVs can be used to derive protective levels for
      any species is not supported by the data. Whereas the use of site-, species-, and
      analyte-specific exposure parameters is recommended to reduce variation in
      exposure estimates (soil protection level), improvement of TRVs is more
      problematic.

PMID- 24944002
TI  - Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble
      carriers: phase equilibria, solid-state characterisation and in
      vivo/pharmacodynamic evaluation.
AB  - OBJECTIVES: The solid-state interactions of fused mixtures nimesulide (ND) with
      polyethylene glycol (PEG) 4000, urea or mannitol were studied through
      constructing thaw-melt phase equilibrium diagrams. METHODS: The solid-state
      characteristics were investigated using differential scanning calorimetry (DSC)
      and X-ray diffraction (XRD). Various types of interactions were identified such
      as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND
      urea and complete solid immiscibility of ND with mannitol. The effects of carrier
      concentrations on the equilibrium solubility and in-vitro dissolution
      characteristics were studied. KEY FINDINGS: Linear increases (R(2)  > 0.99) in
      the aqueous solubility of ND in various concentrations of PEG 4000 and urea were
      obtained, whereas mannitol did not exhibit any effect on the solubility of ND.
      Similar trends were obtained with the dissolution efficiency of the fused
      mixtures of ND with PEG 4000 and urea compared with the corresponding physical
      mixtures and untreated drug. The analgesic effects of untreated ND and the
      selected formulations were investigated by evaluating the drug's ability to
      inhibit the acetic acid-induced writhing response. CONCLUSIONS: The analgesic
      effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with
      urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated
      drug.

PMID- 24944001
TI  - Cytokinin-induced phenotypes in plant-insect interactions: learning from the
      bacterial world.
AB  - Recently, a renewed interest in cytokinins (CKs) has allowed the characterization
      of these phytohormones as key regulatory molecules in plant biotic interactions.
      They have been proved to be instrumental in microbe- and insect-mediated plant
      phenotypes that can be either beneficial or detrimental for the host-plant. In
      parallel, insect endosymbiotic bacteria have emerged as key players in plant
      insect interactions mediating directly or indirectly fundamental aspects of
      insect nutrition, such as insect feeding efficiency or the ability to manipulate
      plant physiology to overcome food nutritional imbalances. However, mechanisms
      that regulate CK production and the role played by insects and their
      endosymbionts remain largely unknown. Against this backdrop, studies on plant
      associated bacteria have revealed fascinating and complex molecular mechanisms
      that lead to the production of bacterial CKs and the modulation of plant-borne
      CKs which ultimately result in profound metabolic and morphological plant
      modifications. This review highlights major strategies used by plant-associated
      bacteria that impact the CK homeostasis of their host-plant, to raise parallels
      with strategies used by phytophagous insects and to discuss the possible role
      played by endosymbiotic bacteria in these CK-mediated plant phenotypes. We
      hypothesize that insects employ a CK-mix production strategy that manipulates the
      phytohormonal balance of their host-plant and overtakes plant gene expression
      causing a metabolic and morphological habitat modification. In addition, insect
      endosymbiotic bacteria may prove to be instrumental in these manipulations
      through the production of bacterial CKs, including specific forms that challenge
      the CK-degrading capacity of the plant (thus ensuring persistent effects) and the
      CK-mediated plant defenses. 

PMID- 24944003
TI  - The influence of laparoscopy on incisional hernia rates: a retrospective analysis
      of 1057 colorectal cancer resections.
AB  - AIM: The aim of this study was to evaluate the incidence of incisional hernia
      formation after laparoscopic and open surgery for colorectal cancer. METHOD: A
      retrospective analysis was conducted of 1057 colorectal cancer resection cases
      (289 laparoscopic, 768 open) performed in a single national laparoscopic training
      centre between January 2006 and December 2011. Clinical notes and serial computed
      tomography scans were reviewed, with any incisional hernia including those at a
      surgical incision, port site, stoma and stoma closure site identified and the
      size of the defect measured. RESULTS: The overall incisional hernia rate was
      14.8%. There was no significant difference between the open and laparoscopic
      groups (14.4% vs 15.9%, P = 0.566). Excluding stoma-related hernia, 10.7% of the
      open group developed a surgical wound hernia, and 11.1% of the laparoscopic group
      developed a hernia at a port site, extraction site or surgical midline incision.
      There was no statistical difference between the two groups (P = 0.853). The
      defects were smaller in the laparoscopic group (P < 0.005). There were
      significantly more parastomal hernias in the laparoscopic group (40%) than in the
      open group (12.7%, P < 0.001). CONCLUSION: The incidence of incisional hernia
      formation was similar after laparoscopic or open surgery for colorectal cancer.
      Parastomal hernia was more frequent after laparoscopic surgery.

PMID- 24944004
TI  - Biomechanical analysis of the splenic avulsion mechanism.
AB  - The spleen is a frequently injured abdominal organ in road accidents, with an
      injury frequency close to 30%. The splenic avulsion exhibit a significant ratio
      of morbidity. It is clinically described as the complete failure of the
      pancreatico-splenic ligament (PSL) which is composed of splenic vessels and
      connective tissues. What are the biomechanical mechanisms involved with spleen
      avulsion? Is it possible to quantify tolerance levels of PSL structure? The
      current work combines both experimental and finite element (FE) investigations to
      determine the splenic avulsion process. Tensile tests on 13 PSL samples were
      performed up to failure. The experimental results provide reference data for
      model validation and showed a failure process starting at a peak force of 70+/-34
      N combined with a peak strain of 105+/-26%. In an attempt to identify possible
      vessel ruptures within the PSL, a FE model of the PSL was developed including
      both vessels and connective tissues. The vessel wall behaviour up to failure was
      reproduced using an Ogden law and calibrated by inverse analysis according to
      literature data. The connective tissues function was modelled by a cohesion-loss
      interface. Once model correlation to experimental results was achieved, numerical
      simulation revealed that haemorrhage could occur even before the maximum peak is
      reached. Indeed, the first vessel ruptures were recorded at a strain of 92% at
      the upper lobe vein.

PMID- 24944005
TI  - Oral vitamin B12 treatment is effective for children with nutritional vitamin B12
      deficiency.
AB  - AIM: Despite being one of common preventable deficiency disorders, vitamin B12
      (vit-B12) deficiency can lead to serious health problems both in children and
      adult. The familiar treatment through parenteral route for vit-B12 deficiency
      frequently leads to poor adherence, and adequate response to treatment has lead
      to interest in oral supplementation. This study investigates the efficacy of oral
      vit-B12 treatment in children with nutritional vit-B12 deficiency. METHODS: Forty
      seven children (from 1 month to 17 years) with vit-B12 levels below 200 pg/mL
      were allocated either of two study groups: Group 1 (1-20 months) and Group 2 (6
      17 years) which were subdivided according to the duration of treatment (Group
      1A&2A: 4 months; Group 1B&2B: 8 months of 1000 MUg oral vit-B12, every day for a
      week, every other day for 2 weeks, 2 days a week for 2 weeks, then once a week).
      RESULTS: Vit-B12 levels among all groups were significantly restored following
      high oral vit-B12 doses (P = 0.013, P = 0.001), the regimen being more effective
      in Group1A and Group1B. Correlation analysis of serum vit-B12 levels and age at
      the end of treatment revealed a decreasing trend with the increasing patient age
      (corelation respectively -65.2%, P = 0.08; -35.4%; P = 0.25). CONCLUSION: Data
      from this study indicate that oral vit-B12 (1000 MUg) for 4 months is effective,
      giving clinicians more choice, for treatment of children with nutritional vit-B12
      deficiency. However, despite this high dose, lower levels were achieved in older
      children indicating the necessity of dosage adjustment in accordance with body
      weight.

PMID- 24944006
TI  - Measurement of ocular cyclotorsion in superior oblique palsy using a single
      Maddox rod.
AB  - BACKGROUND: To describe a modified technique to measure ocular cyclotorsion using
      only 1 Maddox rod and compare it with the traditional double Maddox rod test
      (DMR). METHODS: Ocular cyclotorsion was prospectively measured in 48 consecutive
      patients with superior oblique palsy. Four measurements were taken; 2 using 2
      Maddox rods: (A) a red rod in front of the affected eye and a white rod in front
      of the fellow eye and (B) red rod in front of the sound eye and red in front of
      the affected eye. Two additional sets of measurements were taken using 1 red
      Maddox rod in front of 1 eye only, where horizontal lines in the room served as a
      reference: (C) the red rod in front of the affected eye and (D) the red rod in
      front of the sound eye. RESULTS: Mean ocular cyclotorsion in 48 patients was 6.7
      degrees , 6.8 degrees , 6.6 degrees , and 6.1 degrees  in measures A, B, C, and
      D, respectively. The agreement between A and C did not differ statistically,
      whereas the agreement between B and D was statistically different (P < 0.0001).
      There was high repeatability in both comparisons. CONCLUSIONS: Ocular
      cyclotorsion may be measured using a single Maddox rod instead of two. It is
      simpler to conduct than the DMR.

PMID- 24944009
TI  - Evaluation of the effectiveness of entomopathogens for the management of
      wireworms (Coleoptera: Elateridae) on spring wheat.
AB  - Wireworms, the larval stage of click beetles (Coleoptera: Elateridae), are
      serious soil dwelling pests of small grains, corn, sugar beets, and potatoes.
      Limonius californicus and Hypnoidus bicolor are the predominant wireworm species
      infesting wheat in Montana, particularly in the 'Golden Triangle' area of north
      central Montana. Wireworm populations in field crops are increasing, but
      currently available insecticides provide only partial control, and no alternative
      management tools exist. In our study, three entomopathogenic fungi were tested
      for their efficacy against wireworms in spring wheat at two field locations
      (Ledger and Conrad, Montana, USA) in 2013. The three fungi (Metarhizium brunneum
      F52, Beauveria bassiana GHA, and Metarhizium robertsii DWR 346) were evaluated as
      seed-coat, in-furrow granular, and soil band-over-row drench applications in
      addition to imidacloprid (Gaucho(r) 600) seed treatment (as a chemical check),
      the approach currently being used by growers. Wireworm damage in these treatments
      was evaluated as standing plant counts, wireworm population surveys, and yield.
      The three fungi, applied as formulated granules or soil drenches, and the
      imidacloprid seed treatment all resulted in significantly higher plant stand
      counts and yields at both locations than the fungus-coated seed treatments or the
      untreated control. Significant differences were detected among the application
      methods but not among the species of fungi within each application method. All
      three fungi, when applied as granules in furrow or as soil drenches, were more
      effective than when used as seed-coating treatments for wireworm control, and
      provided an efficacy comparable or superior to imidacloprid. The fungi used in
      this study provided significant plant and yield protection under moderate
      wireworm pressure, supporting their value in the management of this pest. 

PMID- 24944008
TI  - MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA
      in the mouse follicular dendritic cell-like cell line, FL-Y.
AB  - Follicular dendritic cells (FDC) are important stromal cells within the B-cell
      follicles and germinal centres (GC) of secondary lymphoid tissues. FDC trap and
      retain native antigens on their surfaces in the form of immune complexes that
      they display to B cells, in order to select those cells with the highest antigen
      affinity. MicroRNAs are short, non-coding RNAs that are approximately 18-25
      nucleotides in length that regulate gene expression at the post-transcriptional
      level by repressing the translation of target genes. In the current study, in
      vivo and in vitro systems were used to identify microRNAs that were potentially
      expressed by FDC. Constitutive lymphotoxin-beta receptor (LTbetaR) stimulation is
      required to maintain FDC in their differentiated state. We show that the rapid de
      differentiation of spleen FDC that accompanied LTbetaR-blockade, coincided with a
      significant decrease in the expression of mmu-miR-100-5p, mmu-miR-138-5p and mmu
      miR-2137. These microRNAs were shown to be expressed in the FDC-like cell line,
      FL-YB, and specific inhibition of mmu-miR-100-5p significantly enhanced
      expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line. The expression of
      Il6, Ptgs1/2 and Tlr4 by FDC play important roles in regulating GC size and
      promoting high-affinity antibody responses, so it is plausible that mmu-miR-100
      5p may help to regulate the expression of these genes during GC reactions. 

PMID- 24944010
TI  - Influence of miRNA in insulin signaling pathway and insulin resistance: micro
      molecules with a major role in type-2 diabetes.
AB  - The prevalence of type-2 diabetes (T2D) is increasing significantly throughout
      the globe since the last decade. This heterogeneous and multifactorial disease,
      also known as insulin resistance, is caused by the disruption of the insulin
      signaling pathway. In this review, we discuss the existence of various miRNAs
      involved in regulating the main protein cascades in the insulin signaling pathway
      that affect insulin resistance. The influence of miRNAs (miR-7, miR-124a, miR-9,
      miR-96, miR-15a/b, miR-34a, miR-195, miR-376, miR-103, miR-107, and miR-146) in
      insulin secretion and beta (beta) cell development has been well discussed. Here,
      we highlight the role of miRNAs in different significant protein cascades within
      the insulin signaling pathway such as miR-320, miR-383, miR-181b with IGF-1, and
      its receptor (IGF1R); miR-128a, miR-96, miR-126 with insulin receptor substrate
      (IRS) proteins; miR-29, miR-384-5p, miR-1 with phosphatidylinositol 3-kinase
      (PI3K); miR-143, miR-145, miR-29, miR-383, miR-33a/b miR-21 with AKT/protein
      kinase B (PKB) and miR-133a/b, miR-223, miR-143 with glucose transporter 4
      (GLUT4). Insulin resistance, obesity, and hyperlipidemia (high lipid levels in
      the blood) have a strong connection with T2D and several miRNAs influence these
      clinical outcomes such as miR-143, miR-103, and miR-107, miR-29a, and miR-27b. We
      also corroborate from previous evidence how these interactions are related to
      insulin resistance and T2D. The insights highlighted in this review will provide
      a better understanding on the impact of miRNA in the insulin signaling pathway
      and insulin resistance-associated diagnostics and therapeutics for T2D.

PMID- 24944011
TI  - To excise or not: impact of MelaFind on German dermatologists' decisions to
      biopsy atypical lesions.
AB  - OBJECTIVES: To determine the biopsy sensitivity to melanoma of dermatologists in
      Germany and the impact of MelaFind(r) on their decisions to biopsy melanomas.
      DESIGN: Randomized two-armed online reader study presenting case information,
      clinical/dermatoscopic images of pigmented skin lesions and MelaFind results (Arm
      2). METHODS: Each participant was asked to review 130 pigmented skin lesions.
      Biopsy decisions of dermatologists without MelaFind versus MelaFind and
      dermatologists without MelaFind versus dermatologists with MelaFind were
      compared. RESULTS: Dermatologists without MelaFind had average sensitivity to
      melanoma of 69.5 % and average specificity of 55.9 %. MelaFind had greater
      sensitivity than dermatologists alone (96.9 % vs. 69.5 %, one-sided p < 0.00001)
      and lower specificity (9.2 % vs. 55.9 %, one-sided p < 0.00001). Dermatologists
      with MelaFind had higher sensitivity than those without MelaFind (78 % vs. 69.5
      %, one-sided p < 0.00001) and a lower specificity (45.8 % vs. 55.9 %, one-sided p
      < 0.00001). The number of dermatologists detecting over 90 % of melanomas
      increased from 3 of 101 without MelaFind to 22 of 101 with MelaFind (p = 0.00006)
      while specificity remained relatively equivalent (23 % vs. 21 %, p = 0.99).
      CONCLUSIONS: The MelaFind information, when incorporated into the final biopsy
      decision, can improve biopsy sensitivity with modest effect on biopsy
      specificity.

PMID- 24944012
TI  - Trends in hepatitis C treatment uptake in the United States.

PMID- 24944013
TI  - Intrusive memories of hallucinations and delusions in traumatized intensive care
      patients: An interview study.
AB  - OBJECTIVE: Psychological morbidity, including post-traumatic stress disorder
      (PTSD), is common in survivors of intensive care. Intrusive memories of trauma
      are important symptoms of PTSD. Research has not established which aspects of
      intensive care are most traumatizing; invasive medical procedures, fear of dying
      from life-threatening illness or injury, or effects of psychoactive drugs,
      including hallucinations and delusions. Our study aimed to investigate the roots
      of post-intensive care trauma by interviewing survivors with symptoms of PTSD.
      Were their intrusive memories primarily of real events or hallucinations and
      delusions from intensive care? DESIGN: Interview study as part of a mixed-methods
      investigation of psychological outcomes post-intensive care. METHODS: We used
      purposive sampling to identify patients with intrusive memories of intensive care
      unit. Detailed interviews were conducted to investigate the nature and content of
      post-intensive care memories. Intrusive memories were categorized as factual,
      hallucinatory/delusional, or uncertain. RESULTS: Thematic saturation was achieved
      after 17 interviews. Approximately 70% (12/17) of patients had
      hallucinatory/delusional intrusive memories of intensive care, while 12% (2/17)
      had factual but no hallucinatory/delusional memories; 18% (3) were uncertain
      whether memories were factual or hallucinatory/delusional. Further analysis
      suggested that 88% of all patients had hallucinatory/delusional intrusive
      memories. The content of intrusive memories commonly merged realistic events
      (involving intensive care staff, environment, medical procedures and unpleasant
      physical experiences) with delusions and frightening hallucinations. CONCLUSIONS:
      We found that patients in this in-depth study were more traumatized by
      frightening hallucinations/delusions than real events, suggesting they may have
      post-psychosis PTSD, rather than classic PTSD. Interventions are needed to
      diagnose and treat intensive care hallucinations/delusions, or minimize effects,
      to prevent PTSD.

PMID- 24944014
TI  - Glutamate/glutamine metabolism coupling between astrocytes and glioma cells:
      neuroprotection and inhibition of glioma growth.
AB  - Glioma glutamate release has been shown to promote the growth of glioma cells and
      induce neuronal injuries from epilepsy to neuronal death. However, potential
      counteractions from normal astrocytes against glioma glutamate release have not
      been fully evaluated. In this study, we investigated the glutamate/glutamine
      cycling between glioma cells and astrocytes and their impact on neuronal
      function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact
      were established under different mix ratio of astrocyte/glioma. Culture medium
      conditioned in these CGAs were sampled for HPLC measurement, for neuronal
      ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High
      levels of glutaminase expression in glioma cells, but not in astrocytes,
      glutaminase enables glioma cells to release large amount of glutamate in the
      presence of glutamine. (2) Glutamate levels in CGAs were directly determined by
      the astrocyte/glioma ratios, indicating a balance between glioma glutamate
      release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher
      glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe
      neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth
      rate of glioma cells. These results indicate that normal astrocytes in the brain
      play pivotal roles in glioma growth inhibition and in reducing neuronal injuries
      from glioma glutamate release. However, as tumor growth, the protective role of
      astrocytes gradually succumb to glioma cells. 

PMID- 24944015
TI  - Improvement of stability of nitrile hydratase via protein fragment swapping.
AB  - Nitrile hydratase (NHase), which catalyzes the hydration of nitriles to amides,
      is the key enzyme for the production of amides in industries. However, the poor
      stability of this enzyme under the reaction conditions is a drawback of its
      industrial application. In this study, we aimed to improve the stability of NHase
      (PpNHase) from Pseudomonas putida NRRL-18668 using a homologous protein fragment
      swapping strategy. One thermophilic NHase fragment from Comamonas testosteroni 5
      MGAM-4D and two fragments from Pseudonocardia thermophila JCM3095 were selected
      to swap the corresponding fragments of PpNHase. Seven chimeric NHases were
      designed using STAR (site targeted amino recombination) software and molecular
      dynamics to determine the crossover sites for fragment recombination. All
      constructed chimeric NHases showed 1.4- to 3.5-fold enhancement in
      thermostability and six of them become more tolerant to high-concentration
      product. Notably, one of these NHases, 3AB, exhibited a 1.4+/-0.05-fold increase
      in activity compared to the wild-type PpNHase. Circular dichroism spectrum
      analysis and homology modeling revealed that the 3AB slightly differed in
      secondary structure from wild-type PpNHase. The 3AB constructed in this study is
      useful for further industrial application, and the method for designing the
      chimeric protein using homologous protein fragment swapping without a decrease in
      activity may be a strategy to improve the stability of other enzymes. 

PMID- 24944007
TI  - Understanding the spectacular failure of DNA barcoding in willows (Salix): does
      this result from a trans-specific selective sweep?
AB  - Willows (Salix: Salicaceae) form a major ecological component of Holarctic floras
      and consequently are an obvious target for a DNA-based identification system. We
      surveyed two to seven plastid genome regions (~3.8 kb; ~3% of the genome) from 71
      Salix species across all five subgenera, to assess their performance as DNA
      barcode markers. Although Salix has a relatively high level of interspecific
      hybridization, this may not sufficiently explain the near complete failure of
      barcoding that we observed: only one species had a unique barcode. We recovered
      39 unique haplotypes, from more than 500 specimens, that could be partitioned
      into six major haplotype groups. A unique variant of group I (haplotype 1*) was
      shared by 53 species in three of five Salix subgenera. This unusual pattern of
      haplotype sharing across infrageneric taxa is suggestive of either a massive
      nonrandom coalescence failure (incomplete lineage sorting), or of repeated
      plastid capture events, possibly including a historical selective sweep of
      haplotype 1* across taxonomic sections. The former is unlikely as molecular
      dating indicates that haplotype 1* originated recently and is nested in the
      oldest major haplotype group in the genus. Further, we detected significant non
      neutrality in the frequency spectrum of mutations in group I, but not outside
      group I, and demonstrated a striking absence of geographical (isolation by
      distance) effects in the haplotype distributions of this group. The most likely
      explanation for the patterns we observed involves recent repeated plastid capture
      events, aided by widespread hybridization and long-range seed dispersal, but
      primarily propelled by one or more trans-species selective sweeps.

PMID- 24944016
TI  - P44/WDR77 restricts the sensitivity of proliferating cells to TGFbeta signaling.
AB  - We previously reported that a novel WD-40 domain-containing protein, p44/WDR77,
      drives quiescent epithelial cells to re-enter the cell cycle and plays an
      essential role for growth of lung and prostate cancer cells. Transforming growth
      factor beta (TGFbeta) signaling is important in the maintenance of non
      transformed cells in the quiescent or slowly cycling stage. However, both non
      transformed proliferating cells and human cancer cells are non-responsive to
      endogenous TGFbeta signaling. The mechanism by which proliferating cells become
      refractory to TGFbeta inhibition is not well established. Here, we found that
      silencing p44/WDR77 increased cellular sensitivity to TGFbeta signaling and that
      this was inversely correlated with decreased cell proliferation. Smad2 or 3
      phosphorylation, TGFbeta-mediated transcription, and TGFbeta2 and TGFbeta
      receptor type II (TbetaRII) expression were dramatically induced by silencing of
      p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the
      expression of the TGFbeta ligand and its receptor, thereby leading to a cellular
      non-response to TGFbeta signaling. Finally, we found that p44/WDR77 expression
      was correlated with cell proliferation and decreased TGFbeta signaling during
      lung tumorigenesis. Together, these results suggest that p44/WDR77 expression
      causes the non-sensitivity of proliferating cells to TGFbeta signaling, thereby
      contributing to cellular proliferation during lung tumorigenesis. 

PMID- 24944017
TI  - PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation
      factor-5 in association with activation of the Smad pathway.
AB  - We have previously demonstrated promotion by growth differentiation factor-5
      (GDF5) of brown adipogenesis for systemic energy expenditure through a mechanism
      relevant to activating the bone morphological protein (BMP) receptor/mothers
      against decapentaplegic homolog (Smad)/peroxisome proliferator-activated receptor
      gamma co-activator 1alpha (PGC-1alpha) pathway. Here, we show the involvement of
      the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in brown adipogenesis
      mediated by GDF5. Overexpression of GDF5 in cells expressing adipocyte protein-2
      markedly accelerated the phosphorylation of Smad1/5/8 and Akt in white and brown
      adipose tissues. In brown adipose tissue from heterozygous GDF5(Rgsc451) mutant
      mice expressing a dominant-negative (DN) GDF5 under obesogenic conditions, the
      basal phosphorylation of Smad1/5/8 and Akt was significantly attenuated. Exposure
      to GDF5 not only promoted the phosphorylation of both Smad1/5/8 and Akt in
      cultured brown pre-adipocytes, but also up-regulated Pgc1a and uncoupling protein
      1 expression in a manner sensitive to the PI3K/Akt inhibitor Ly294002 as well as
      retroviral infection with DN-Akt. GDF5 drastically promoted BMP-responsive
      luciferase reporter activity in a Ly294002-sensitive fashion. Both Ly294002 and
      DN-Akt markedly inhibited phosphorylation of Smad5 in the nuclei of brown pre
      adipocytes. These results suggest that PI3K/Akt signals play a role in the GDF5
      mediated brown adipogenesis through a mechanism related to activation of the Smad
      pathway. 

PMID- 24944018
TI  - Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer
      stem cell traits.
AB  - Atractylenolide I (AT-I), one of the main naturally occurring compounds of
      Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various
      cancers. However, its effects on the treatment of gastric cancer remain unclear.
      Via multiple cellular and molecular approaches, we demonstrated that AT-I could
      potently inhibit cancer cell proliferation and induce apoptosis through
      inactivating Notch pathway. AT-I treatment led to the reduction of expressions of
      Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I
      inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by
      suppression of their sphere formation capacity and cell viability. AT-I
      attenuated gastric cancer stem cell (GCSC) traits partly through inactivating
      Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1
      and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a
      potential therapeutic drug for the treatment of gastric cancer. 

PMID- 24944019
TI  - Cerebellar stem cells do not produce neurons and astrocytes in adult mouse.
AB  - Although previous studies implied that cerebellar stem cells exist in some adult
      mammals, little is known about whether these stem cells can produce new neurons
      and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.)
      injection, we found that there are abundant BrdU(+) cells in adult mouse
      cerebellum, and their quantity and density decreases significantly over time. We
      also found cell proliferation rate is diversified in different cerebellar
      regions. Among these BrdU(+) cells, very few are mash1(+) or nestin(+) stem
      cells, and the vast majority of cerebellar stem cells are quiescent. Data
      obtained by in vivo retrovirus injection indicate that stem cells do not produce
      neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by
      retrovirus are Iba1(+) microglia. These results indicate that very few stem cells
      exist in adult mouse cerebellum, and none of these stem cells contribute to
      neurogenesis and astrogenesis under physiological condition. 

PMID- 24944020
TI  - Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins
      that have been desynchronized with advanced age.
AB  - It is well established that lipid metabolism is controlled, in part, by circadian
      clocks. However, circadian clocks lose temporal precision with age and correlates
      with elevated incidence in dyslipidemia and metabolic syndrome in older adults.
      Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in
      aged animals, we hypothesized that LA affects the circadian clock to achieve
      these results. We fed 24 month old male F344 rats a diet supplemented with 0.2%
      (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock
      protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused
      a significant phase-shift in the expression patterns of the circadian clock
      proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse
      Erythroblastosis virus (Rev-erb) beta without altering the amplitude of protein
      levels during the light phase of the day. LA also significantly altered the
      oscillatory patterns of clock-controlled proteins associated with lipid
      metabolism. The level of peroxisome proliferator-activated receptor (PPAR) alpha
      was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid
      synthase (FAS) were both significantly reduced, suggesting that the LA
      supplemented aged animals are in a catabolic state. We conclude that LA
      remediates some of the dyslipidemic processes associated with advanced age, and
      this mechanism may be at least partially through entrainment of circadian clocks.

PMID- 24944021
TI  - Estradiol determines the effects of PTH on ERalpha-dependent transcription in
      MC3T3-E1 cells.
AB  - Bone remodeling is a continuous process regulated by several hormones such as
      estrogens and parathyroid hormone (PTH). Here we investigated the influence of
      PTH on estrogen receptor alpha (ERalpha)-dependent transcriptional activity in
      MC3T3-E1 osteoblasts. Cells that were transfected with an ER-responsive reporter
      plasmid and treated with PTH showed increased luciferase activity. However, in
      the presence of 17beta-estradiol, we observed that PTH inhibited ERalpha-mediated
      transcription. cAMP mimicked the effects by PTH, and the findings were confirmed
      in COS-1 cells transfected with expression vector encoding the catalytic subunit
      of cAMP-dependent protein kinase (PKA). Furthermore, PTH exhibited specific
      effects on the mRNA expression of the decoy receptor osteoprotegerin (OPG) and
      the receptor activator of NF kappa-B ligand (RANKL) in MC3T3-E1 osteoblasts. In
      the absence of 17beta-estradiol, PTH and cAMP enhanced the OPG/RANKL ratio,
      whereas, OPG/RANKL was suppressed when estradiol was present. In conclusion, our
      results indicate that the presence of estradiol determines whether PTH and cAMP
      stimulates or inhibits ERalpha-dependent activity and the OPG/RANKL mRNA
      expression in an osteoblastic cell line. 

PMID- 24944022
TI  - NMR conformational properties of an Anthrax Lethal Factor domain studied by
      multiple amino acid-selective labeling.
AB  - NMR-based structural biology urgently needs cost- and time-effective methods to
      assist both in the process of acquiring high-resolution NMR spectra and their
      subsequent analysis. Especially for bigger proteins (>20 kDa) selective labeling
      is a frequently used means of sequence-specific assignment. In this work we
      present the successful overexpression of a polypeptide of 233 residues,
      corresponding to the structured part of the N-terminal domain of Anthrax Lethal
      Factor, using Escherichia coli expression system. The polypeptide was
      subsequently isolated in pure, soluble form and analyzed structurally by solution
      NMR spectroscopy. Due to the non-satisfying quality and resolution of the spectra
      of this 27 kDa protein, an almost complete backbone assignment became feasible
      only by the combination of uniform and novel amino acid-selective labeling
      schemes. Moreover, amino acid-type selective triple-resonance NMR experiments
      proved to be very helpful.

PMID- 24944023
TI  - A microplate assay for the coupled transglycosylase-transpeptidase activity of
      the penicillin binding proteins; a vancomycin-neutralizing tripeptide combination
      prevents penicillin inhibition of peptidoglycan synthesis.
AB  - A microplate, scintillation proximity assay to measure the coupled
      transglycosylase-transpeptidase activity of the penicillin binding proteins in
      Escherichia coli membranes was developed. Membranes were incubated with the two
      peptidoglycan sugar precursors UDP-N-acetyl muramylpentapeptide (UDP-MurNAc(pp))
      and UDP-[(3)H]N-acetylglucosamine in the presence of 40 MUM vancomycin to allow
      in situ accumulation of lipid II. In a second step, vancomycin inhibition was
      relieved by addition of a tripeptide (Lys-D-ala-D-ala) or UDP-MurNAc(pp),
      resulting in conversion of lipid II to cross-linked peptidoglycan. Inhibitors of
      the transglycosylase or transpeptidase were added at step 2. Moenomycin, a
      transglycosylase inhibitor, had an IC50 of 8 nM. Vancomycin and nisin also
      inhibited the assay. Surprisingly, the transpeptidase inhibitors penicillin and
      ampicillin showed no inhibition. In a pathway assay of peptidoglycan synthesis,
      starting from the UDP linked sugar precursors, inhibition by penicillin was
      reversed by a 'neutral' combination of vancomycin plus tripeptide, suggesting an
      interaction thus far unreported.

PMID- 24944025
TI  - Bromide-bridged palladium(III) chain complexes showing charge bistability near
      room temperature.
AB  - We synthesized and characterized bromide-bridged Pd(III) chain complexes,
      [Pd(en)2Br](MalCn-Y)2.H2O (en = ethylenediamine; MalCn-Y = dialkyl sulfomalonate;
      n: the number of carbon atoms) (n = 7 and 12). The compound with n = 7 showed
      charge-bistability near room temperature. In addition, it is shown that the
      Pd(III) state is maintained in the thin film state.

PMID- 24944024
TI  - In silico assessment of S100A12 monomer and dimer structural dynamics:
      implications for the understanding of its metal-induced conformational changes.
AB  - Changes in the concentration of different ions modulate several cellular
      processes, such as Ca(2+) and Zn(2+) in inflammation. Upon activation of immune
      system effector cells, the intracellular Ca(2+) concentration rises propagating
      the activation signal, leading to degranulation and generation of reactive oxygen
      species, which increases the Zn(2+) intracellular concentration as a consequence
      of the cellular antioxidant machinery. In this context, S100A12 is of special
      interest because it is a pro-inflammatory protein expressed in neutrophils whose
      structure and function are modulated by both Ca(2+) and Zn(2+). The current
      hypothesis about its mechanism of action was built based on biochemical and
      crystallographic data. However, there are missing connections between molecular
      structure and the way in which many events are concatenated at the triggering and
      along the inflammatory process. In this work we use molecular dynamics
      simulations to describe how variations in Zn(2+) and Ca(2+) concentrations
      modulate the structural dynamics of the calcium-free S100A12 dimer and monomer,
      which was not considered a part of the mechanism of action before. Our results
      suggest that (i) Zn(2+) have a determinant role in the dimerization step, as well
      as in the unbinding of the Na(+) complexed to the N-terminal EF-hand; (ii) the N
      terminal EF-hand domain is the first to bind Ca(2+), and not the C-terminal, as
      usually accepted; and that (iii) Ca(2+) modulates the structural dynamics of H
      III. 

PMID- 24944026
TI  - Steroidogenesis-adrenal cell signal transduction.
AB  - The purpose of this article is to review fundamentals in adrenal gland
      histophysiology. Key findings regarding the important signaling pathways involved
      in the regulation of steroidogenesis and adrenal growth are summarized. We
      illustrate how adrenal gland morphology and function are deeply interconnected in
      which novel signaling pathways (Wnt, Sonic hedgehog, Notch, beta-catenin) or
      ionic channels are required for their integrity. Emphasis is given to exploring
      the mechanisms and challenges underlying the regulation of proliferation, growth,
      and functionality. Also addressed is the fact that while it is now well-accepted
      that steroidogenesis results from an enzymatic shuttle between mitochondria and
      endoplasmic reticulum, key questions still remain on the various aspects related
      to cellular uptake and delivery of free cholesterol. The significant progress
      achieved over the past decade regarding the precise molecular mechanisms by which
      the two main regulators of adrenal cortex, adrenocorticotropin hormone (ACTH) and
      angiotensin II act on their receptors is reviewed, including structure-activity
      relationships and their potential applications. Particular attention has been
      given to crucial second messengers and how various kinases, phosphatases, and
      cytoskeleton-associated proteins interact to ensure homeostasis and/or meet
      physiological demands. References to animal studies are also made in an attempt
      to unravel associated clinical conditions. Many of the aspects addressed in this
      article still represent a challenge for future studies, their outcome aimed at
      providing evidence that the adrenal gland, through its steroid hormones, occupies
      a central position in many situations where homeostasis is disrupted, thus
      highlighting the relevance of exploring and understanding how this key organ is
      regulated. (c) 2014 American Physiological Society. Compr Physiol 4:889-964,
      2014. 

PMID- 24944028
TI  - Thermal stress and toxicity.
AB  - Elevating ambient temperature above thermoneutrality exacerbates toxicity of most
      air pollutants, insecticides, and other toxic chemicals. On the other hand,
      safety and toxicity testing of toxicants and drugs is usually performed in mice
      and rats maintained at sub-thermoneutral temperatures of ~22?C. When exposed to
      chemical toxicants under these relatively cool conditions, rodents typically
      undergo a regulated hypothermic response, characterized by preference for cooler
      ambient temperatures and controlled reduction in core temperature. Reducing core
      temperature delays the clearance of most toxicants from the body; however, a mild
      hypothermia also improves recovery and survival from the toxicant. Raising
      ambient temperature to thermoneutrality and above increases the rate of clearance
      of the toxicant but also exacerbates toxicity. Furthermore, heat stress combined
      with work or exercise is likely to worsen toxicity. Body temperature of large
      mammals, including humans, does not decrease as much in response to exposure to a
      toxicant. However, heat stress can nonetheless worsen toxic outcome in humans
      through a variety of mechanisms. For example, heat-induced sweating and elevation
      in skin blood flow accelerates uptake of some insecticides. Epidemiological
      studies suggest that thermal stress may exacerbate the toxicity of airborne
      pollutants such as ozone and particulate matter. Overall, translating results of
      studies in rodents to that of humans is a formidable task attributed in part to
      the interspecies differences in thermoregulatory response to the toxicants and to
      thermal stress.

PMID- 24944029
TI  - Regulation of aldosterone synthesis and secretion.
AB  - Aldosterone is a steroid hormone synthesized in and secreted from the outer layer
      of the adrenal cortex, the zona glomerulosa. Aldosterone is responsible for
      regulating sodium homeostasis, thereby helping to control blood volume and blood
      pressure. Insufficient aldosterone secretion can lead to hypotension and
      circulatory shock, particularly in infancy. On the other hand, excessive
      aldosterone levels, or those too high for sodium status, can cause hypertension
      and exacerbate the effects of high blood pressure on multiple organs,
      contributing to renal disease, stroke, visual loss, and congestive heart failure.
      Aldosterone is also thought to directly induce end-organ damage, including in the
      kidneys and heart. Because of the significance of aldosterone to the physiology
      and pathophysiology of the cardiovascular system, it is important to understand
      the regulation of its biosynthesis and secretion from the adrenal cortex. Herein,
      the mechanisms regulating aldosterone production in zona glomerulosa cells are
      discussed, with a particular emphasis on signaling pathways involved in the
      secretory response to the main controllers of aldosterone production, the renin
      angiotensin II system, serum potassium levels and adrenocorticotrophic hormone.
      The signaling pathways involved include phospholipase C-mediated phosphoinositide
      hydrolysis, inositol 1,4,5-trisphosphate, cytosolic calcium levels, calcium
      influx pathways, calcium/calmodulin-dependent protein kinases, diacylglycerol,
      protein kinases C and D, 12-hydroxyeicostetraenoic acid, phospholipase D, mitogen
      activated protein kinase pathways, tyrosine kinases, adenylate cyclase, and cAMP
      dependent protein kinase. A complete understanding of the signaling events
      regulating aldosterone biosynthesis may allow the identification of novel targets
      for therapeutic interventions in hypertension, primary aldosteronism, congestive
      heart failure, renal disease, and other cardiovascular disorders.

PMID- 24944030
TI  - Thermoregulatory modeling for cold stress.
AB  - Modeling for cold stress has generated a rich history of innovation, has exerted
      a catalytic influence on cold physiology research, and continues to impact human
      activity in cold environments. This overview begins with a brief summation of
      cold thermoregulatory model development followed by key principles that will
      continue to guide current and future model development. Different representations
      of the human body are discussed relative to the level of detail and prediction
      accuracy required. In addition to predictions of shivering and vasomotor
      responses to cold exposure, algorithms are presented for thermoregulatory
      mechanisms. Various avenues of heat exchange between the human body and a cold
      environment are reviewed. Applications of cold thermoregulatory modeling range
      from investigative interpretation of physiological observations to forecasting
      skin freezing times and hypothermia survival times. While these advances have
      been remarkable, the future of cold stress modeling is still faced with
      significant challenges that are summarized at the end of this overview.

PMID- 24944031
TI  - Pathophysiology, diagnosis, and treatment of mineralocorticoid disorders.
AB  - The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood
      pressure control, fluid, and electrolyte balance in humans. Chronic activation of
      mineralocorticoid production leads to dysregulation of the cardiovascular system
      and to hypertension. The key mineralocorticoid is aldosterone. Hyperaldosteronism
      causes sodium and fluid retention in the kidney. Combined with the actions of
      angiotensin II, chronic elevation in aldosterone leads to detrimental effects in
      the vasculature, heart, and brain. The adverse effects of excess aldosterone are
      heavily dependent on increased dietary salt intake as has been demonstrated in
      animal models and in humans. Hypertension develops due to complex genetic
      influences combined with environmental factors. In the last two decades, primary
      aldosteronism has been found to occur in 5% to 13% of subjects with hypertension.
      In addition, patients with hyperaldosteronism have more end organ manifestations
      such as left ventricular hypertrophy and have significant cardiovascular
      complications including higher rates of heart failure and atrial fibrillation
      compared to similarly matched patients with essential hypertension. The
      pathophysiology, diagnosis, and treatment of primary aldosteronism will be
      extensively reviewed. There are many pitfalls in the diagnosis and confirmation
      of the disorder that will be discussed. Other rare forms of hyper- and hypo
      aldosteronism and unusual disorders of hypertension will also be reviewed in this
      article.

PMID- 24944032
TI  - Sex differences in the HPA axis.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is a major component of the systems
      that respond to stress, by coordinating the neuroendocrine and autonomic
      responses. Tightly controlled regulation of HPA responses is critical for
      maintaining mental and physical health, as hyper- and hypo-activity have been
      linked to disease states. A long history of research has revealed sex differences
      in numerous components of the HPA stress system and its responses, which may
      partially form the basis for sex disparities in disease development. Despite
      this, many studies use male subjects exclusively, while fewer reports involve
      females or provide direct sex comparisons. The purpose of this article is to
      present sex comparisons in the functional and molecular aspects of the HPA axis,
      through various phases of activity, including basal, acute stress, and chronic
      stress conditions. The HPA axis in females initiates more rapidly and produces a
      greater output of stress hormones. This review focuses on the interactions
      between the gonadal hormone system and the HPA axis as the key mediators of these
      sex differences, whereby androgens increase and estrogens decrease HPA activity
      in adulthood. In addition to the effects of gonadal hormones on the adult
      response, morphological impacts of hormone exposure during development are also
      involved in mediating sex differences. Additional systems impinging on the HPA
      axis that contribute to sex differences include the monoamine neurotransmitters
      norepinephrine and serotonin. Diverse signals originating from the brain and
      periphery are integrated to determine the level of HPA axis activity, and these
      signals are, in many cases, sex-specific.

PMID- 24944033
TI  - Decompression and decompression sickness.
AB  - The ever-present desire of humankind to explore new limits introduced us to the
      syndrome of decompression sickness (DCS). This broad overview of DCS is aimed at
      its pathophysiology and basics of therapeutic strategies. After a brief
      explanation of decompression theory, historical vignettes will serve to inform
      the practical application of our increasing understanding of DCS risks. The
      pathophysiology, current practices, role of bubble monitoring, risk factors, and
      potential long-term effects of DCS are also discussed. The goal is to explain the
      current state of DCS understanding in the context of a robust observational and
      empirical history. However, DCS remains a syndrome consisting of a constellation
      of symptoms following a change in ambient pressure. Though great strides have
      been made, significant knowledge gaps remain. If the coming years advance the
      field even a fraction of what its predecessors accomplished, the health and
      safety of those who endeavor in the environment of changing pressures most
      certainly will be improved.

PMID- 24944036
TI  - Saturation diving; physiology and pathophysiology.
AB  - In saturation diving, divers stay under pressure until most of their tissues are
      saturated with breathing gas. Divers spend a long time in isolation exposed to
      increased partial pressure of oxygen, potentially toxic gases, bacteria, and
      bubble formation during decompression combined with shift work and long periods
      of relative inactivity. Hyperoxia may lead to the production of reactive oxygen
      species (ROS) that interact with cell structures, causing damage to proteins,
      lipids, and nucleic acid. Vascular gas-bubble formation and hyperoxia may lead to
      dysfunction of the endothelium. The antioxidant status of the diver is an
      important mechanism in the protection against injury and is influenced both by
      diet and genetic factors. The factors mentioned above may lead to production of
      heat shock proteins (HSP) that also may have a negative effect on endothelial
      function. On the other hand, there is a great deal of evidence that HSPs may also
      have a "conditioning" effect, thus protecting against injury. As people age,
      their ability to produce antioxidants decreases. We do not currently know the
      capacity for antioxidant defense, but it is reasonable to assume that it has a
      limit. Many studies have linked ROS to disease states such as cancer, insulin
      resistance, diabetes mellitus, cardiovascular diseases, and atherosclerosis as
      well as to old age. However, ROS are also involved in a number of protective
      mechanisms, for instance immune defense, antibacterial action, vascular tone, and
      signal transduction. Low-grade oxidative stress can increase antioxidant
      production. While under pressure, divers change depth frequently. After such
      changes and at the end of the dive, divers must follow procedures to decompress
      safely. Decompression sickness (DCS) used to be one of the major causes of injury
      in saturation diving. Improved decompression procedures have significantly
      reduced the number of reported incidents; however, data indicate considerable
      underreporting of injuries. Furthermore, divers who are required to return to the
      surface quickly are under higher risk of serious injury as no adequate
      decompression procedures for such situations are available. Decompression also
      leads to the production of endothelial microparticles that may reduce endothelial
      function. As good endothelial function is a documented indicator of health that
      can be influenced by regular exercise, regular physical exercise is recommended
      for saturation divers. Nowadays, saturation diving is a reasonably safe and well
      controlled method for working under water. Until now, no long-term impact on
      health due to diving has been documented. However, we still have limited
      knowledge about the pathophysiologic mechanisms involved. In particular we know
      little about the effect of long exposure to hyperoxia and microparticles on the
      endothelium.

PMID- 24944038
TI  - Retraction Notice to: Agonist-induced GPCR shedding from the ciliary surface is
      dependent on ESCRT-III and VPS4.

PMID- 24944027
TI  - The multifaceted mineralocorticoid receptor.
AB  - The primary adrenal cortical steroid hormones, aldosterone, and the
      glucocorticoids cortisol and corticosterone, act through the structurally similar
      mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial
      for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the
      significantly more abundant glucocorticoids are indispensable for energy
      homeostasis, appropriate responses to stress, and limiting inflammation. Steroid
      receptors initiate gene transcription for proteins that effect their actions as
      well as rapid non-genomic effects through classical cell signaling pathways. GR
      and MR are expressed in many tissues types, often in the same cells, where they
      interact at molecular and functional levels, at times in synergy, others in
      opposition. Thus the appropriate balance of MR and GR activation is crucial for
      homeostasis. MR has the same binding affinity for aldosterone, cortisol, and
      corticosterone. Glucocorticoids activate MR in most tissues at basal levels and
      GR at stress levels. Inactivation of cortisol and corticosterone by 11beta-HSD2
      allows aldosterone to activate MR within aldosterone target cells and limits
      activation of the GR. Under most conditions, 11beta-HSD1 acts as a reductase and
      activates cortisol/corticosterone, amplifying circulating levels. 11beta-HSD1 and
      MR antagonists mitigate inappropriate activation of MR under conditions of
      oxidative stress that contributes to the pathophysiology of the cardiometabolic
      syndrome; however, MR antagonists decrease normal MR/GR functional interactions,
      a particular concern for neurons mediating cognition, memory, and affect.

PMID- 24944037
TI  - HPA axis-rhythms.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis regulates circulating levels of
      glucocorticoid hormones, and is the major neuroendocrine system in mammals that
      provides a rapid response and defense against stress. Under basal (i.e.,
      unstressed) conditions, glucocorticoids are released with a pronounced circadian
      rhythm, characterized by peak levels of glucocorticoids during the active phase,
      that is daytime in humans and nighttime in nocturnal animals such as mice and
      rats. When studied in more detail, it becomes clear that the circadian rhythm of
      the HPA axis is characterized by a pulsatile release of glucocorticoids from the
      adrenal gland that results in rapid ultradian oscillations of hormone levels both
      in the blood and within target tissues, including the brain. In this review, we
      discuss the regulation of these circadian and ultradian HPA rhythms, how these
      rhythms change in health and disease, and how they affect the physiology and
      behavior of the organism.

PMID- 24944039
TI  - Coffee and chocolate in danger.
AB  - As a rapidly growing global consumer base appreciates the pleasures of coffee and
      chocolate and health warnings are being replaced by more encouraging sounds from
      medical experts, their supply is under threat from climate change, pests and
      financial problems. Coffee farmers in Central America, in particular, are highly
      vulnerable to the impact of climate change, made worse by financial insecurity.
      Michael Gross reports. 

PMID- 24944040
TI  - Charles Spence.
AB  - Working at the Crossmodal Research Laboratory in Oxford, Charles Spence tries to
      apply the latest insights from our growing neuroscience understanding of the
      rules governing multisensory integration to the design of better products,
      packages, places, interfaces, and foods, an area that can perhaps best be
      captured under the title of neuroscience-inspired multisensory design. 

PMID- 24944034
TI  - Autonomic nervous system and immune system interactions.
AB  - The present review assesses the current state of literature defining integrative
      autonomic-immune physiological processing, focusing on studies that have employed
      electrophysiological, pharmacological, molecular biological, and central nervous
      system experimental approaches. Central autonomic neural networks are informed of
      peripheral immune status via numerous communicating pathways, including neural
      and non-neural. Cytokines and other immune factors affect the level of activity
      and responsivity of discharges in sympathetic and parasympathetic nerves
      innervating diverse targets. Multiple levels of the neuraxis contribute to
      cytokine-induced changes in efferent parasympathetic and sympathetic nerve
      outflows, leading to modulation of peripheral immune responses. The functionality
      of local sympathoimmune interactions depends on the microenvironment created by
      diverse signaling mechanisms involving integration between sympathetic nervous
      system neurotransmitters and neuromodulators; specific adrenergic receptors; and
      the presence or absence of immune cells, cytokines, and bacteria. Functional
      mechanisms contributing to the cholinergic anti-inflammatory pathway likely
      involve novel cholinergic-adrenergic interactions at peripheral sites, including
      autonomic ganglion and lymphoid targets. Immune cells express adrenergic and
      nicotinic receptors. Neurotransmitters released by sympathetic and
      parasympathetic nerve endings bind to their respective receptors located on the
      surface of immune cells and initiate immune-modulatory responses. Both
      sympathetic and parasympathetic arms of the autonomic nervous system are
      instrumental in orchestrating neuroimmune processes, although additional studies
      are required to understand dynamic and complex adrenergic-cholinergic
      interactions. Further understanding of regulatory mechanisms linking the
      sympathetic nervous, parasympathetic nervous, and immune systems is critical for
      understanding relationships between chronic disease development and immune
      associated changes in autonomic nervous system function.

PMID- 24944041
TI  - Evaluation of the effect of food and ketoconazole on the pharmacokinetics of the
      smoothened inhibitor PF-04449913 in healthy volunteers.
AB  - PURPOSE: To evaluate the effect of a potent cytochrome P450 3A4 (CYP3A4)
      inhibitor, ketoconazole, and separately the effect of food on PF-04449913
      pharmacokinetics in healthy volunteers. METHODS: This was an open-label, two
      sequence, three-period, three-treatment, single-dose, crossover study. Subjects
      were randomized to receive single doses of 200 mg PF-04449913 after an overnight
      fast or after consuming a high-fat meal during Period 1 or 2, with a washout
      period of at least 8 days. In Period 3, all subjects received ketoconazole (400
      mg/day) (days 1-7) and a co-administered single 200-mg PF-04449913 dose (day 4).
      RESULTS: Geometric mean ratio of PF-04449913 in the presence of ketoconazole
      versus PF-04449913 alone was 2.40 [90% confidence interval (CI) 2.15, 2.68] for
      area under the plasma concentration-time curve from time zero to infinity (AUC(0
      inf)) and 1.40 (90% CI 1.24, 1.58) for peak plasma concentration (C max). The
      geometric mean ratio for fed state compared with fasted state for AUC(0-inf) was
      0.87 (90% CI 0.78, 0.97) and for C max was 0.66 (90% CI 0.56, 0.78). PF-04449913
      was well tolerated, and all adverse events were mild to moderate. CONCLUSIONS: PF
      04449913 plasma exposures and peak concentrations were increased following
      concurrent administration of ketoconazole in healthy volunteers. These findings
      provide the upper limit for expected PF-04449913 exposures after co
      administration of a strong CYP3A4 inhibitor in patients with cancer who routinely
      receive antifungal azoles. While a high-fat meal decreased PF-04449913 exposure,
      the differences in plasma exposure under the two conditions were not considered
      clinically meaningful.

PMID- 24944043
TI  - Chilling-related cell damage of apple (Malus * domestica Borkh.) fruit cortical
      tissue impacts antioxidant, lipid and phenolic metabolism.
AB  - 'Soggy breakdown' (SB) is an internal flesh disorder of 'Honeycrisp' apple (Malus
      * domestica Borkh.) fruit that occurs during low temperature storage. The
      disorder is a chilling injury (CI) in which visible symptoms typically appear
      after several weeks of storage, but information about the underlying metabolism
      associated with its induction and development is lacking. The metabolic profile
      of flesh tissue from wholly healthy fruit and brown and healthy tissues from
      fruit with SB was characterized using gas chromatography-mass spectrometry (GC
      MS) and liquid chromatograph-mass spectrometry (LC-MS). Partial least squares
      discriminant analysis (PLS-DA) and correlation networks revealed correlation
      among ester volatile compounds by composition and differences in phytosterol,
      phenolic and putative triacylglycerides (TAGs) metabolism among the tissues.
      anova-simultaneous component analysis (ASCA) was used to test the significance of
      metabolic changes linked with tissue health status. ASCA-significant components
      included antioxidant compounds, TAGs, and phytosterol conjugates. Relative to
      entirely healthy tissues, elevated metabolite levels in symptomatic tissue
      included gamma-amino butyric acid, glycerol, sitosteryl (6'-O-palmitoyl) beta-d
      glucoside and sitosteryl (6'-O-stearate) beta-d-glucoside, and TAGs containing
      combinations of 16:0, 18:3, 18:2 and 18:1 fatty acids. Reduced metabolite levels
      in SB tissue included 5-caffeoyl quinate, beta-carotene, catechin, epicatechin,
      alpha-tocopherol, violaxanthin and sitosteryl beta-d glucoside. Pathway analysis
      indicated aspects of primary metabolism differed according to tissue condition,
      although differences in metabolites involved were more subtle than those of some
      secondary metabolites. The results implicate oxidative stress and membrane
      disruption processes in SB development and constitute a diagnostic metabolic
      profile for the disorder. 

PMID- 24944042
TI  - Roles of small RNAs in soybean defense against Phytophthora sojae infection.
AB  - The genus Phytophthora consists of many notorious pathogens of crops and forestry
      trees. At present, battling Phytophthora diseases is challenging due to a lack of
      understanding of their pathogenesis. We investigated the role of small RNAs in
      regulating soybean defense in response to infection by Phytophthora sojae, the
      second most destructive pathogen of soybean. Small RNAs, including microRNAs
      (miRNAs) and small interfering RNAs (siRNAs), are universal regulators that
      repress target gene expression in eukaryotes. We identified known and novel small
      RNAs that differentially accumulated during P. sojae infection in soybean roots.
      Among them, miR393 and miR166 were induced by heat-inactivated P. sojae hyphae,
      indicating that they may be involved in soybean basal defense. Indeed, knocking
      down the level of mature miR393 led to enhanced susceptibility of soybean to P.
      sojae; furthermore, the expression of isoflavonoid biosynthetic genes was
      drastically reduced in miR393 knockdown roots. These data suggest that miR393
      promotes soybean defense against P. sojae. In addition to miRNAs, P. sojae
      infection also resulted in increased accumulation of phased siRNAs (phasiRNAs)
      that are predominantly generated from canonical resistance genes encoding
      nucleotide binding-leucine rich repeat proteins and genes encoding
      pentatricopeptide repeat-containing proteins. This work identifies specific
      miRNAs and phasiRNAs that regulate defense-associated genes in soybean during
      Phytophthora infection. 

PMID- 24944045
TI  - CEA monitoring in colorectal cancer is not a waste of time.

PMID- 24944046
TI  - Jean Decima Jacomb (1894-1988), matron of The London Clinic, 20 Devonshire Place,
      London W1 from 1938 to 1949.
AB  - Miss Jean Jacomb born into a wealthy family, was at the age of 22 a student nurse
      at St Bartholomew's Hospital, London in 1917 where she nursed convalescent
      soldiers from World War I. Her midwifery training was in the slums around
      Whitechapel where a nurses uniform and medical bag provided a safe passage in the
      East End of London. For a while she worked in South Africa and India and
      returning to UK in 1923 she progressed to appointment as matron at the now re
      named Royal Marsden Hospital in Chelsea. In 1938 she was appointed matron to The
      London Clinic during the years of World War II following which in 1949 she
      retired at the age of 55. She then travelled the world extensively by ship,
      always first class. She died in 1988. 

PMID- 24944044
TI  - Use of hyaluronidase for pharmacokinetic increase in bioavailability of
      intracutaneously applied substances.
AB  - Endogenous hyaluronidases in the human body have physiological and
      pathophysiological significance due to their enzymatic activity during the
      cleavage of hyaluronan. The potential of therapeutic use of testicular and
      recombinant hyaluronidase has been increasingly acknowledged and developed in
      recent years. Most relevant in practice is the co-application of hyaluronidase
      and other active substances in order to enhance their bioavailability within the
      tissue.

PMID- 24944047
TI  - Lesser known aspects of Ludwik Fleck's (1896-1961) heroic life during World War
      II.
AB  - Professor Ludwik Fleck was a famous scientist and a prominent philosopher.
      Although his life and work were studied extensively, the Second World War period
      was a subject of some discussion and controversy. On account of his Jewish
      origin, he was first arrested and moved from the Lwow ghetto to the 'Laokoon'
      factory and then imprisoned in KL Auschwitz-Birkenau and in KL Buchenwald. Fleck
      produced the anti-typhus vaccine in the chemo-bacteriological laboratory in the
      Jewish Hospital at Kuszewicza Street and in the 'Laokoon' factory in Lwow. During
      his incarceration in KL Auschwitz-Birkenau, Fleck worked in the camp laboratory
      in Block 10 carrying out bacteriological studies for the inmates and then was
      assigned to work in the Wasserman station in Rajsko. From January 1944 Fleck
      performed routine laboratory tests in Block 50 in KL Buchenwald. Though Fleck had
      a privileged life in the camp, he participated in the sabotage activities
      organized by the camp resistance. 

PMID- 24944048
TI  - Medical memorials of the Heroic Age of Antarctic exploration.
AB  - The Heroic Age of Antarctic exploration spanned the period from 1895 to 1922.
      Medical men who took part in the expeditions of that period made significant
      contributions to the expeditions in medical treatment of expedition members,
      geographical discovery and science and, as a result of such contributions, many
      had geographical features named after them. A recent paper listed five doctors
      from the Heroic Age who were so honoured. We now add biographical precises of a
      further 17 personnel, including two medical students who have geographical
      features named after them. 

PMID- 24944049
TI  - Stefan Jellinek (1871-1968): The only professor of electro-pathology.
AB  - The exploding use of electricity in homes and industry in the second half of the
      19th century was accompanied by many injuries and fatalities from electric
      currents. Their study by my father was the serendipitous outcome of his early
      work on possible blood pressure changes from electric currents in a career that
      started in internal medicine. It became his limited field of electro-pathology
      which embraced first aid, the care of the injured, histopathology and accident
      prevention. He was an enthusiastic teacher and collector of specimens, from tree
      trunks struck by lightning down to the microscopy of accidental and experimental
      electric lesions. 

PMID- 24944050
TI  - The enigmatic figure of Dr Henry Maudsley (1835-1918).
AB  - In spite of his contribution to psychiatry in 19th century Britain, Henry
      Maudsley remains a mysterious figure, a man mostly known for his donation to the
      London County Council for the building of the Maudsley Hospital and for The
      Maudsley Annual Lecture created in honour of his benevolence. Besides Sir Aubrey
      Lewis' article in 1951 and Michael Collie's attempt in 1988 to construct a
      biographical study on Maudsley, there does not seem to be any current endeavour
      to tell the story of his life, whereas Trevor Turner's contribution to the 2004
      Oxford Dictionary of National Biography gives a somewhat scathing but
      unattributed account of Maudsley's personality. This essay attempts to explore
      his contributions to the Medico-Psychological Association (MPA), the current
      Royal College of Psychiatrists, his editorship of the Journal of Mental Health
      (currently named the British Journal of Psychiatry), his literary contributions
      and his vision for a psychiatric hospital. This essay is an attempt to demystify
      his figure and to explore some of the rumours and criticisms surrounding his name
      and the reasons why so little has been written about him. It is also a venture to
      unravel his complex personality and his intricate philosophy. 

PMID- 24944051
TI  - The development of artificial organs and prostheses worldwide and in the Ottoman
      Empire.
AB  - An artificial organ or prosthesis is a man-made device that is implanted or
      integrated into a human to replace a natural organ. There were many historical
      steps in the development of artificial organs and prostheses. New surgical
      techniques, the development of prosthetic materials and the creative ideas of
      engineers led to progress in this field. 

PMID- 24944035
TI  - Classical Renin-Angiotensin system in kidney physiology.
AB  - The renin-angiotensin system has powerful effects in control of the blood
      pressure and sodium homeostasis. These actions are coordinated through integrated
      actions in the kidney, cardiovascular system and the central nervous system.
      Along with its impact on blood pressure, the renin-angiotensin system also
      influences a range of processes from inflammation and immune responses to
      longevity. Here, we review the actions of the "classical" renin-angiotensin
      system, whereby the substrate protein angiotensinogen is processed in a two-step
      reaction by renin and angiotensin converting enzyme, resulting in the sequential
      generation of angiotensin I and angiotensin II, the major biologically active
      renin-angiotensin system peptide, which exerts its actions via type 1 and type 2
      angiotensin receptors. In recent years, several new enzymes, peptides, and
      receptors related to the renin-angiotensin system have been identified,
      manifesting a complexity that was previously unappreciated. While the functions
      of these alternative pathways will be reviewed elsewhere in this journal, our
      focus here is on the physiological role of components of the "classical" renin
      angiotensin system, with an emphasis on new developments and modern concepts.

PMID- 24944052
TI  - A biography of William Tuke (1732-1822): Founder of the modern mental asylum.
AB  - William Tuke was a 19th-century reformist and philanthropist notable for his work
      in mental health. He was known for his strict self-discipline and judicious
      manner. He was also a firm believer in the Quaker faith and actively supported
      the group and employed many of their principles in his work, especially in his
      chef d'oeuvre, The Retreat, established in 1792, a mental asylum in York.
      Possibly catalysed by the very public mismanagement of King George III's
      'madness', he pioneered the use of moral treatment, a new humane method of
      treating mental illness. This focussed on allowing patients to live in a
      community, partake in daily activities and not be subjected to the brutality of
      the commonplace asylum, all of which were very rare in the treatment of lunatics
      at that time. Described as 'The Period of Humane Reform', his work coincided with
      the emergence of similar approaches in France, most famously by Philippe Pinel
      (1745-1826) and his pupil Jean Esquirol (1772-1840) in Paris. Tuke eventually
      went on to aid in the reform of the law with regards to asylums. 

PMID- 24944053
TI  - Specific maltose derivatives modulate the swarming motility of nonswarming mutant
      and inhibit bacterial adhesion and biofilm formation by Pseudomonas aeruginosa.
AB  - We have demonstrated that specific synthetic maltose derivatives activate the
      swarming motility of a Pseudomonas aeruginosa nonswarming mutant (rhlA) at low
      concentration, but inhibit it at high concentration. Although these molecules are
      not microbicidal, active maltose derivatives with bulky hydrocarbon groups
      inhibited bacterial adhesion, and exhibited biofilm inhibition and dispersion
      (IC50 ~20 MUM and DC50 ~30 MUM, respectively). Because the swarming motility of
      the rhlA mutant is abolished by the lack natural rhamnolipids, the swarming
      activation suggests that maltose derivatives are analogues of rhamnolipids.
      Together, these results suggest a new approach of controlling multiple bacterial
      activities (bacterial adhesion, biofilm formation, and swarming motility) by a
      set of disaccharide-based molecules.

PMID- 24944055
TI  - Adherence to dietary guidelines and mortality: a report from prospective cohort
      studies of 134,000 Chinese adults in urban Shanghai.
AB  - BACKGROUND: A higher adherence to dietary recommendations, such as the Dietary
      Approaches to Stop Hypertension (DASH) and the Alternative Healthy Eating Index
      (AHEI), has been associated with lower morbidity and mortality from chronic
      diseases in Western populations. However, the health benefits of following the
      Dietary Guidelines for Chinese remain unknown. OBJECTIVE: We examined adherence
      to the Chinese Food Pagoda (CHFP) in association with total and cause-specific
      mortality and compared associations with those of the DASH and AHEI. DESIGN:
      Participants included 61,239 men and 73,216 women (aged 40-74 y) from 2
      population-based prospective studies in Shanghai, China. Habitual dietary intakes
      were assessed at baseline in-person interviews by using validated food-frequency
      questionnaires. Deaths and underlying causes were identified through the Shanghai
      Vital Statistics Registry and follow-up home visits. RESULTS: We documented 2954
      deaths in men and 4348 deaths in women during mean follow-ups of 6.5 and 12.0 y,
      respectively. A higher CHFP score was associated with lower total mortality with
      multivariable-adjusted HRs of 0.67 (95% CI: 0.60, 0.75) in men and 0.87 (95% CI:
      0.80, 0.95) in women when extreme quartiles were compared (both P-trend < 0.005).
      Decreased risks associated with a higher CHFP score were observed for
      cardiovascular disease, cancer, and diabetes mortality, particularly in men. A
      significantly lower total mortality was shown for adherence to specific
      recommendations on vegetables, fruit, legumes, fish, and eggs but not grains,
      dairy, meat, fat, and salt. A higher DASH score and AHEI also predicted lower
      mortality from all causes, cardiovascular disease, and diabetes but not cancer.
      CONCLUSIONS: A greater compliance with Chinese or US dietary guidelines is
      associated with lower total mortality in Chinese adults. Favorable associations
      are more evident in men than women and more consistent for cardiometabolic
      mortality than cancer mortality.

PMID- 24944054
TI  - Effects of whole and refined grains in a weight-loss diet on markers of metabolic
      syndrome in individuals with increased waist circumference: a randomized
      controlled-feeding trial.
AB  - BACKGROUND: Higher whole-grain (WG) intake is associated with a lower prevalence
      of metabolic syndrome (MetS); however, there is inconsistent clinical evidence
      with regard to the benefit of WGs compared with refined grains (RGs) on MetS.
      OBJECTIVE: We hypothesized that consuming WGs in the place of RGs would improve
      MetS criteria in individuals with or at risk of MetS. DESIGN: A randomized,
      controlled, open-label parallel study was conducted in 50 overweight and obese
      individuals with increased waist circumference and one or more other MetS
      criteria. Participants consumed a controlled weight-loss diet containing either
      WG or RG (control) products for 12 wk. Body composition, MetS criteria and
      related markers, and plasma alkylresorcinols (compliance marker of WG intake)
      were measured at baseline and at 6 and 12 wk. A subgroup (n = 28) underwent
      magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue
      (AT). RESULTS: Baseline variables were not significantly different between
      groups; however, the RG group tended to have higher triglycerides and lower high
      density lipoprotein (HDL) cholesterol (P = 0.06). Alkylresorcinols increased with
      consumption of the WG diet and did not change with consumption of the RG diet
      (time * treatment, P < 0.0001), which showed dietary compliance. There were no
      differences in anthropometric changes between groups; however, weight, body mass
      index, and percentage of body AT decreased at both 6 and 12 wk (P < 0.05), and
      reductions in percentage of abdominal AT occurred by 6 wk and did not change
      between 6 and 12 wk (P = 0.09). Both glucose (P = 0.02) and HDL cholesterol (P =
      0.04) were lower with the consumption of the WG compared with the RG diet.
      However, when noncompliant individuals (n = 3) were removed, the glucose effect
      was stronger (P = 0.01) and the HDL-cholesterol effect was no longer significant
      (P = 0.14). CONCLUSIONS: Replacing RGs with WGs within a weight-loss diet does
      not beneficially affect abdominal AT loss and has modest effects on markers of
      MetS. WGs appear to be effective at normalizing blood glucose concentrations,
      especially in those individuals with prediabetes.

PMID- 24944056
TI  - Maternal dietary glycemic index and glycemic load in early pregnancy are
      associated with offspring adiposity in childhood: the Southampton Women's Survey.
AB  - BACKGROUND: Maternal hyperglycemia in pregnancy is associated with greater
      adiposity in offspring. The glycemic index (GI) and glycemic load (GL) describe
      the glycemic response to carbohydrate ingestion. However, the influence of
      maternal dietary GI and GL in pregnancy on childhood adiposity is unknown.
      OBJECTIVE: We examined relations of maternal dietary GI and GL in early and late
      pregnancy with offspring body composition. DESIGN: A total of 906 mother-child
      pairs from the prospective cohort the Southampton Women's Survey were included.
      Children underwent dual-energy X-ray absorptiometry measurements of body
      composition at birth and 4 and 6 y of age. Log-transformed fat mass and lean mass
      were standardized with a mean (+/-SD) of 0 +/- 1. Maternal dietary GI and GL were
      assessed at 11 and 34 wk of gestation by using an administered food-frequency
      questionnaire. RESULTS: After control for potential confounders, both maternal
      dietary GI and GL in early pregnancy were positively associated with fat mass at
      4 and 6 y of age [fat mass SDs per 10-unit GI increase: beta = 0.43 (95% CI:
      0.06, 0.80), P = 0.02 at 4 y of age; beta = 0.40 (95% CI: 0.10, 0.70), P = 0.01
      at 6 y of age; fat mass SDs per 50-unit GL increase: beta = 0.43 (95% CI: 0.19,
      0.67), P < 0.001 at 4 y of age; beta = 0.27 (95% CI: 0.07, 0.47), P = 0.007 at 6
      y of age]. In contrast, there were no associations between maternal dietary GI or
      GL in late pregnancy and offspring fat mass at these ages. Maternal dietary GI
      and GL were not associated with fat mass at birth or offspring lean mass at any
      of the ages studied. CONCLUSION: Higher maternal dietary GI and GL in early
      pregnancy are associated with greater adiposity in childhood.

PMID- 24944057
TI  - Appetite control and biomarkers of satiety with vegetarian (soy) and meat-based
      high-protein diets for weight loss in obese men: a randomized crossover trial.
AB  - BACKGROUND: There is limited evidence with regard to the effect of different
      sources of protein on appetite during weight loss. Vegetarian and meat-based high
      protein diets may have contrasting effects on appetite and biomarkers of protein
      induced satiety. OBJECTIVE: The aim was to assess appetite response to meat or
      vegetarian high-protein weight-loss (HPWL) diets in obese men to monitor plasma
      amino acid profile and gut peptide response as potential satiety biomarkers.
      DESIGN: Twenty obese [body mass index (in kg/m2): 34.8] men participated in a
      dietary intervention study. After 3 d of a maintenance diet, they were provided
      in a crossover design with either a vegetarian HPWL (Soy-HPWL) or a meat-based
      HPWL (Meat-HPWL) diet for 2 wk. Both diets comprised 30% protein, 30% fat, and
      40% carbohydrate, provided to measured resting metabolic rate. Body weight and
      the motivation to eat were measured daily. Plasma satiety biomarkers were
      collected during a test-meal challenge (5 h) at the end of each diet period.
      RESULTS: Over the 2 wk, subjects lost, on average, 2.41 and 2.27 kg with
      consumption of the Soy- and Meat-HPWL diets, respectively [P = 0.352; SE of the
      difference (SED): 0.1]. ANOVA confirmed that subjectively rated hunger (P =
      0.569; SED: 3.8), fullness (P = 0.404; SED: 4.1), desire to eat (P = 0.356; SED:
      3.7), preservation of lean body mass (P = 0.334; SED: 0.2), and loss of
      percentage fat mass (P = 0.179; SED: 0.2) did not differ between the 2 HPWL
      diets. There were differences in absolute concentrations of ghrelin and peptide
      YY between the 2 HPWL diets, although the response as net area under the curve
      was not different. CONCLUSIONS: Appetite control and weight loss were similar for
      both HPWL diets. Gut hormone profile was similar between the diets, which
      suggests that vegetarian diets can be as effective as meat-based diets for
      appetite control during weight loss.

PMID- 24944058
TI  - Umami flavor enhances appetite but also increases satiety.
AB  - BACKGROUND: Monosodium glutamate (MSG) has been shown to increase satiety when
      combined with protein. Inosine 5'-monophosphate acts synergistically with MSG
      when tasted, is present in high-protein sources, and may potentially further
      enhance satiety. OBJECTIVE: We assessed effects of a combination of monosodium
      glutamate and inosine 5'-monophosphate (MSG/IMP) provided either alone or in a
      high-energy, high-carbohydrate and -protein soup on appetite during ingestion and
      postingestive satiety. DESIGN: Fixed portions (450 g) of a low-energy control and
      high-energy, high-carbohydrate and -protein soup preload with added monosodium
      glutamate and inosine 5'-monophosphate (MSG/IMP+) or without added monosodium
      glutamate and inosine 5'-monophosphate (MSG/IMP-) were consumed on 4
      nonconsecutive days, and changes in appetite during soup intake and at a
      subsequent ad libitum lunch were assessed in 26 low-restraint volunteers by using
      a within-participant design. RESULTS: MSG/IMP+ conditions significantly reduced
      subsequent intake more than the MSG/IMP- condition did irrespective of energy.
      The high-carbohydrate and -protein condition also reduced intake independently of
      MSG/IMP. Energy compensation was greater in the MSG/IMP+ carbohydrate and protein
      conditions than MSG/IMP- condition. The addition of the MSG/IMP+ also increased
      the soup pleasantness and caused an immediate increase in appetite when the soup
      was first tasted. CONCLUSION: The addition of MSG/IMP to a low-energy preload had
      a biphasic effect on appetite by stimulating appetite during ingestion and
      enhancing postingestive satiety.

PMID- 24944059
TI  - Food insecurity and dietary quality in US adults and children: a systematic
      review.
AB  - BACKGROUND: Food insecurity is adversely associated with the physical and mental
      health of adults and children, and the mechanism that underlies this association
      has been assumed to be dietary intake of lower quality in food insecure than food
      secure individuals. A thorough understanding of observed associations between
      food insecurity and dietary quality is needed to test this assumption and may
      highlight pathways through which to improve the health of food-insecure adults
      and children. OBJECTIVE: We systematically reviewed all evidence of associations
      between food insecurity and dietary quality and contrasted associations observed
      in adults and those for children. DESIGN: Evidence came from studies that
      appeared in indexed, peer-reviewed journals and 1) sampled US residents, 2)
      separately sampled children and adults, 3) contained a measure of food insecurity
      or food insufficiency, and 4) included at least one measure of dietary quality.
      RESULTS: In adults, 170 associations between food insecurity and dietary quality
      were tested, and 50 associations (29%) suggested an adverse association. Food
      insecure adults consumed fewer vegetables, fruit, and dairy products than did
      food secure adults and had lower intake of vitamins A and B-6, calcium,
      magnesium, and zinc. In children, 130 associations were tested, and 21
      associations (16%) showed an adverse association. There was substantial evidence
      of only lower fruit consumption in food-insecure compared with food-secure
      children. Reporting and publication biases may have contributed to an
      overestimation of the association between food insecurity and dietary quality.
      CONCLUSIONS: Food insecurity is adversely associated with dietary quality in
      adults, particularly intakes of nutrient-rich vegetables, fruit, and dairy that
      promote good health. However, food insecurity was less-consistently associated
      with lower dietary quality in children. The idea that parents effectively shield
      their children from compromised dietary quality because of food shortages is
      supported by the evidence.

PMID- 24944060
TI  - Low-calorie sweeteners and body weight and composition: a meta-analysis of
      randomized controlled trials and prospective cohort studies.
AB  - BACKGROUND: Replacement of caloric sweeteners with lower- or no-calorie
      alternatives may facilitate weight loss or weight maintenance by helping to
      reduce energy intake; however, past research examining low-calorie sweeteners
      (LCSs) and body weight has produced mixed results. OBJECTIVE: The objective was
      to systematically review and quantitatively evaluate randomized controlled trials
      (RCTs) and prospective cohort studies, separately, that examined the relation
      between LCSs and body weight and composition. DESIGN: A systematic literature
      search identified 15 RCTs and 9 prospective cohort studies that examined LCSs
      from foods or beverages or LCSs consumed as tabletop sweeteners. Meta-analyses
      generated weighted mean differences in body weight and composition values between
      the LCS and control groups among RCTs and weighted mean correlations for LCS
      intake and these parameters among prospective cohort studies. RESULTS: In RCTs,
      LCSs modestly but significantly reduced all outcomes examined, including body
      weight (-0.80 kg; 95% CI: -1.17, -0.43), body mass index [BMI (in kg/m2): -0.24;
      95% CI: -0.41, -0.07], fat mass (-1.10 kg; 95% CI: -1.77, -0.44), and waist
      circumference (-0.83 cm; 95% CI: -1.29, -0.37). Among prospective cohort studies,
      LCS intake was not associated with body weight or fat mass, but was significantly
      associated with slightly higher BMI (0.03; 95% CI: 0.01, 0.06). CONCLUSIONS: The
      current meta-analysis provides a rigorous evaluation of the scientific evidence
      on LCSs and body weight and composition. Findings from observational studies
      showed no association between LCS intake and body weight or fat mass and a small
      positive association with BMI; however, data from RCTs, which provide the highest
      quality of evidence for examining the potentially causal effects of LCS intake,
      indicate that substituting LCS options for their regular-calorie versions results
      in a modest weight loss and may be a useful dietary tool to improve compliance
      with weight loss or weight maintenance plans.

PMID- 24944061
TI  - Fried-food consumption and risk of type 2 diabetes and coronary artery disease: a
      prospective study in 2 cohorts of US women and men.
AB  - BACKGROUND: Through the processes of oxidation, polymerization, and
      hydrogenation, the cooking method of frying modifies both foods and their frying
      medium. However, it remains unknown whether the frequent consumption of fried
      foods is related to long-term cardiometabolic health. OBJECTIVE: We examined
      fried-food consumption and risk of developing incident type 2 diabetes (T2D) or
      coronary artery disease (CAD). DESIGN: Fried-food consumption was assessed by
      using a questionnaire in 70,842 women from the Nurses' Health Study (1984-2010)
      and 40,789 men from the Health Professionals Follow-Up Study (1986-2010) who were
      free of diabetes, cardiovascular disease, and cancer at baseline. Time-dependent
      Cox proportional hazards models were used to estimate RRs and 95% CIs for T2D and
      CAD adjusted for demographic, diet, lifestyle, and other cardiometabolic risk
      factors. Results were pooled by using an inverse variance-weighted random-effects
      meta-analysis. RESULTS: We documented 10,323 incident T2D cases and 5778 incident
      CAD cases. Multivariate-adjusted RRs (95% CIs) for individuals who consumed fried
      foods <1, 1-3, 4-6, or >=7 times/wk were 1.00 (reference), 1.15 (0.97, 1.35),
      1.39 (1.30, 1.49), and 1.55 (1.32, 1.83), respectively, for T2D and 1.00
      (reference), 1.06 (0.98, 1.15), 1.23 (1.14, 1.33), and 1.21 (1.06, 1.39),
      respectively, for CAD. Associations were largely attenuated when we further
      controlled for biennially updated hypertension, hypercholesterolemia, and body
      mass index. CONCLUSIONS: Frequent fried-food consumption was significantly
      associated with risk of incident T2D and moderately with incident CAD, and these
      associations were largely mediated by body weight and comorbid hypertension and
      hypercholesterolemia.

PMID- 24944062
TI  - Folic acid handling by the human gut: implications for food fortification and
      supplementation.
AB  - BACKGROUND: Current thinking, which is based mainly on rodent studies, is that
      physiologic doses of folic acid (pterylmonoglutamic acid), such as dietary
      vitamin folates, are biotransformed in the intestinal mucosa and transferred to
      the portal vein as the natural circulating plasma folate, 5-methyltetrahydrofolic
      acid (5-MTHF) before entering the liver and the wider systemic blood supply.
      OBJECTIVE: We tested the assumption that, in humans, folic acid is biotransformed
      (reduced and methylated) to 5-MTHF in the intestinal mucosa. DESIGN: We conducted
      a crossover study in which we sampled portal and peripheral veins for labeled
      folate concentrations after oral ingestion with physiologic doses of stable
      isotope-labeled folic acid or the reduced folate 5-formyltetrahydrofolic acid (5
      FormylTHF) in 6 subjects with a transjugular intrahepatic porto systemic shunt
      (TIPSS) in situ. The TIPSS allowed blood samples to be taken from the portal
      vein. RESULTS: Fifteen minutes after a dose of folic acid, 80 +/- 12% of labeled
      folate in the hepatic portal vein was unmodified folic acid. In contrast, after a
      dose of labeled 5-FormylTHF, only 4 +/- 18% of labeled folate in the portal vein
      was unmodified 5-FormylTHF, and the rest had been converted to 5-MTHF after 15
      min (postdose). CONCLUSIONS: The human gut appears to have a very efficient
      capacity to convert reduced dietary folates to 5-MTHF but limited ability to
      reduce folic acid. Therefore, large amounts of unmodified folic acid in the
      portal vein are probably attributable to an extremely limited mucosal cell
      dihydrofolate reductase (DHFR) capacity that is necessary to produce
      tetrahydrofolic acid before sequential methylation to 5-MTHF. This process would
      suggest that humans are reliant on the liver for folic acid reduction even though
      it has a low and highly variable DHFR activity. Therefore, chronic liver exposure
      to folic acid in humans may induce saturation, which would possibly explain
      reports of systemic circulation of unmetabolized folic acid.

PMID- 24944063
TI  - Effect of egg ingestion on trimethylamine-N-oxide production in humans: a
      randomized, controlled, dose-response study.
AB  - BACKGROUND: It is important to understand whether eating eggs, which are a major
      source of dietary choline, results in increased exposure to trimethylamine-N
      oxide (TMAO), which is purported to be a risk factor for developing heart
      disease. OBJECTIVE: We determined whether humans eating eggs generate TMAO and,
      if so, whether there is an associated increase in a marker for inflammation [ie,
      high-sensitivity C-reactive protein (hsCRP)] or increased oxidation of low
      density lipoprotein (LDL). DESIGN: In a longitudinal, double-blind, randomized
      dietary intervention, 6 volunteers were fed breakfast doses of 0, 1, 2, 4, or 6
      egg yolks. Diets were otherwise controlled on the day before and day of each egg
      dose with a standardized low-choline menu. Plasma TMAO at timed intervals
      (immediately before and 1, 2, 4, 8, and 24 h after each dose), 24-h urine TMAO,
      predose and 24-h postdose serum hsCRP, and plasma oxidized LDL were measured.
      Volunteers received all 5 doses with each dose separated by >2-wk washout
      periods. RESULTS: The consumption of eggs was associated with increased plasma
      and urine TMAO concentrations (P < 0.01), with ~14% of the total choline in eggs
      having been converted to TMAO. There was considerable variation between
      individuals in the TMAO response. There was no difference in hsCRP or oxidized
      LDL concentrations after egg doses. CONCLUSIONS: The consumption of >=2 eggs
      results in an increased formation of TMAO. Choline is an essential nutrient that
      is required for normal human liver and muscle functions and important for normal
      fetal development. Additional study is needed to both confirm the association
      between TMAO and atherosclerosis and identify factors, microbiota and genetic,
      that influence the generation of TMAO before policy and medical recommendations
      are made that suggest reduced dietary choline intake.

PMID- 24944065
TI  - Evaluation of the tamper-resistant properties of tapentadol extended-release
      tablets: results of in vitro laboratory analyses.
AB  - OBJECTIVE: To evaluate tamper-resistant properties of tapentadol tablets
      formulated with polyethylene oxide (PEO) matrix. DESIGN: Analytical and physical
      tests to characterize tablets. INTERVENTIONS: Tapentadol extended release (ER)
      50, 100, 150, 200, and 250 mg. MAIN OUTCOME MEASURE(S): Mechanical resistance of
      tapentadol ER tablets to crushing (all doses), in vitro drug-release profiles of
      intact and tampered 50- and 250-mg tablets, and resistance to extraction of 250
      mg tablets subjected to hammering. RESULTS: Crush resistance testing showed no
      deformation of tablets with two metal spoons, minimal deformation (no
      pulverization/breakage) with a pill crusher, slight deformation with a
      standardized pharmacopeia breaking force tester, and flattening (no
      pulverization/breakage) with a standardized hammer instrument. Mean in vitro
      release profiles in quality control medium (0.050 M phosphate buffer, pH 6.8)
      were similar with intact and tampered (pill crusher) tablets; the release profile
      was faster for hammered than intact tablets, with 30 percent of the drug released
      after 30 minutes (slightly higher than maximum release allowed per drug product
      specifications). Intact tablets were completely resistant to extraction in most
      organic solvents tested; in aqueous solvents, the amount of drug extracted
      increased with time. Hammered tablets were less resistant to extraction but
      required vigorous shaking over extended periods of time to release >50 percent of
      active ingredient. CONCLUSIONS: In vitro results from tampering attempts
      presented herein demonstrate that tapentadol ER tablets were resistant to these
      forms of physical manipulation. Tapentadol ER tablets were also generally
      resistant to dissolution in most solvents. Developing tamper-resistant
      formulations is an important step in strategies to mitigate opioid abuse.

PMID- 24944064
TI  - Snail cooperates with Kras G12D in vivo to increase stem cell factor and enhance
      mast cell infiltration.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced fibro
      inflammatory stromal reaction that contributes to tumor progression. A critical
      step in invasion and metastasis is the epithelial-to-mesenchymal transition
      (EMT), which can be regulated by the Snail family of transcription factors.
      Overexpression of Snail (Snai1) and mutant Kras(G12D) in the pancreas of
      transgenic mice, using an elastase (EL) promoter, resulted in fibrosis. To
      identify how Snail modulates inflammation in the pancreas, we examined the effect
      of expressing Snail in EL-Kras(G12D) mice (Kras(G12D)/Snail) on mast cell
      infiltration, which has been linked to PDAC progression. Using this animal model
      system, it was demonstrated that there are increased numbers of mast cells in the
      pancreas of Kras(G12D)/Snail mice compared with control Kras(G12D) mice. In
      addition, it was revealed that human primary PDAC tumors with increased Snail
      expression are associated with increased mast cell infiltration, and that Snail
      expression in these clinical specimens positively correlated with the expression
      of stem cell factor (SCF/KITLG), a cytokine known to regulate mast cell
      migration. Concomitantly, SCF levels are increased in the Kras(G12D)/Snail mice
      than in control mice. Moreover, overexpression of Snail in PDAC cells increased
      SCF levels, and the media conditioned by Snail-expressing PDAC cells promoted
      mast cell migration. Finally, inhibition of SCF using a neutralizing antibody
      significantly attenuated Snail-induced migration of mast cells. IMPLICATIONS:
      Together, these results elucidate how the EMT regulator Snail contributes to
      inflammation associated with PDAC tumors.

PMID- 24944067
TI  - Patient aberrant drug taking behaviors in a large family medicine residency
      program: a retrospective chart review of screening practices, incidence, and
      predictors.
AB  - INTRODUCTION: Potentially aberrant drug-taking behaviors (pADTB) are described as
      any departure from strict adherence to prescribed use of medications for their
      intended indication. There are several validated instruments, processes, and
      databases available to assist the clinician in screening and stratifying risk for
      patients in which controlled substances are being prescribed or considered.
      Actual utilization of these tools in nonspecialist healthcare settings is largely
      unknown. The primary objective of this retrospective chart review was to describe
      utilization patterns of these common tools within a 56 physician family medicine
      training program. Secondary objectives included identification of site-specific
      predictors of pADTB and correlation of prescribing patterns with documented
      aberrant behaviors. METHODS: A total of 202 chronic pain patients were identified
      for inclusion based on prior 12-month prescription and refill records within the
      electronic health record (EHR) from March 2008 through March 2009. Each patient
      included had at least one opioid for 30 days within the study period and had
      chronic pain symptoms for at least 90 days. Each chart was reviewed for
      predefined pADTB, controlled substance refill request, prescription drug
      monitoring profile, and post hoc investigator completion of the Opioid Risk Tool
      Clinician Form. Descriptive statistics and regression analysis was used to report
      results. RESULTS: Clinician documentation of risk-screening tool use of any type
      was limited to one patient of the 202 records reviewed. Within this sample, 203
      unique pADTB were documented in the EHR records of 89 (44.1 percent) patients.
      Patients prescribed morphine or tramadol appeared to exhibit less use of multiple
      prescribers and multiple pharmacies while an association between this behavior
      and two or more concurrent opioid prescriptions became apparent. Those taking
      fentanyl or morphine exhibited unsanctioned dose escalations more frequently.
      CONCLUSIONS: These results suggest that routine evaluation of risk for abuse or
      misuse of opioid analgesics occurs infrequently in a large family medicine
      training program. pADTB exhibited by patients using opioids for chronic pain
      syndromes in this sample were consistent with those reported in other similar
      settings. Policies and procedures in primary care settings for improved risk
      evaluation and ongoing monitoring of chronic opioid therapy is needed.

PMID- 24944066
TI  - Implementation of a collaborative care management program with buprenorphine in
      primary care: a comparison between opioid-dependent patients and patients with
      chronic pain using opioids nonmedically.
AB  - OBJECTIVE: To implement a collaborative care management program with
      buprenorphine in a primary care clinic. DESIGN: Prospective observational study.
      SETTING: A busy urban academic primary care clinic affiliated with a tertiary
      care hospital. PARTICIPANTS: Opioid-dependent patients or patients with chronic
      pain using opioids nonmedically were recruited for the study. A total of 45
      participants enrolled. INTERVENTIONS: Patients were treated with buprenorphine
      and managed by a supervising psychiatrist, pharmacist care manager, and health
      coaches. The care manager conducted buprenorphine inductions and all follow-up
      visits. Health coaches offered telephonic support. The psychiatrist supervised
      both the care manager and health coaches. MAIN OUTCOME MEASURES: Primary outcomes
      were treatment retention at 6 months, and change in the proportion of aberrant
      toxicology results and opioid craving scores from baseline to 6 months. After
      data collection, clinical outcomes were compared between opioid-dependent
      patients and patients with chronic pain using opioids nonmedically. Overall, 55.0
      percent of participants (25/45) remained in treatment at 6 months. Primary care
      physicians (PCPs)' attitudes about opioid dependence treatment were surveyed at
      baseline and at 18 months. RESULTS: Forty-three patients (95.6 percent) accepted
      treatment and 25 (55.0 percent) remained in treatment at 6 months. The proportion
      of aberrant urine toxicology results decreased significantly from baseline to 6
      months (p < 0.01). Craving scores significantly decreased from baseline to 6
      months (p < 0.01). Opioid-dependent patients, as opposed to patients with chronic
      pain using opioids nonmedically, were significantly more likely to complete 6
      months of treatment (p < 0.05). PCPs' confidence in treating opioid dependence in
      primary care increased significantly from baseline to 18 months
      postimplementation (p < 0.01). CONCLUSION: Collaborative care management for
      opioid dependence with buprenorphine may be feasible in a primary care clinic.
      More research is needed to understand the role of buprenorphine in managing
      patients with chronic pain using opioids nonmedically.

PMID- 24944069
TI  - An evaluation of the performance of the Opioid Manager clinical tool in primary
      care: a qualitative study.
AB  - AIMS: The Opioid Manager (OM) is a point-of-care paper tool for physicians, which
      summarizes the Canadian Guideline for Safe and Effective Use of Opioids for
      Chronic Non-Cancer Pain. To evaluate the efficacy of the OM, there is a need to
      better understand how physicians are using the OM, and how it is relevant to
      their practice. METHODS: Semistructured interviews were conducted with six family
      physicians in Ontario with clinical pain management experience. The interviews
      were analyzed using content analysis. The technique of "code-recode" was
      conducted by two analysts to verify content validity. RESULTS: The following main
      themes emerged: 1) OM as a communication tool; 2) OM as an educational tool; 3)
      OM as a clinical tool; 4) OM content/design; 5) OM benefits; 6) who the OM is
      used with; 7) OM potential; and 8) challenges of pain management. Physicians'
      commented the OM was a useful reference for helping their clinical decision
      making regarding opioids, and used it to educate and communicate with their
      patients/colleagues. Although many felt the content/design of the OM had a number
      of good features, there was a need for modifications (ie, merge with other tools
      and create electronic version). Given the challenges associated with pain
      management, a number of benefits were derived from using the OM (ie, protection
      and building therapeutic alliance), and respondents' felt the tool had the
      potential to meet a number of unmet needs related to opioid management.
      CONCLUSIONS: Overall, the OM was viewed positively for improving pain management
      practices but further work is required to refine the tool's potential.

PMID- 24944068
TI  - Observations on hydrocodone and its metabolites in oral fluid specimens of the
      pain population: comparison with urine.
AB  - OBJECTIVE: Hydrocodone undergoes metabolism via cytochrome P450 (CYP) 3A4 (N
      demethylation) to norhydrocodone and via CYP2D6 (O-demethylation) to
      hydromorphone. Hydrocodone, hydromorphone, and norhydrocodone are excreted in
      urine and secreted in saliva. The goal was to characterize hydrocodone and its
      metabolites in oral fluid specimens of a pain population and compare to urine
      specimens. DESIGN: This retrospective analysis included more than 8,500 oral
      fluid specimens and more than 250,000 urine specimens collected between March and
      June 2012 that were sent to Millennium Laboratories (San Diego, CA) and analyzed
      for hydrocodone, hydromorphone, and norhydrocodone using liquid chromatography
      tandem mass spectrometry. Statistical analyses and linear regressions were
      conducted using Microsoft Excel(r) 2010 and OriginPro v8.6. RESULTS: The median
      oral fluid concentrations of hydrocodone and norhydrocodone were 122 and 7.7
      ng/mL, respectively. However, the oral fluid concentrations of hydromorphone were
      below detection in many specimens (<1 ng/mL). The positive detection rate of
      parent drug and metabolites in oral fluid (17-31 percent detection rates) was
      much lower than in urine (63-75 percent detection rates). The geometric median
      metabolic ratio (MR) of norhydrocodone to hydrocodone was 0.07 in oral fluid and
      1.2 in urine. The observed hydrocodone oral fluid concentrations were
      approximately 10-fold greater than previously reported plasma concentrations.
      CONCLUSION: Oral fluid had a much lower norhydrocodone to hydrocodone MR compared
      to urine. Reference ranges for oral fluid drug concentrations should not be
      extrapolated from plasma ranges. The observed ranges of secreted hydrocodone and
      metabolite concentrations in oral fluid should help determine reference ranges
      for medication monitoring.

PMID- 24944070
TI  - A chart review based comparative study of retention rates for two dispensing
      regimens for buprenorphine for subjects with opioid dependence at a tertiary care
      substance use disorder treatment center.
AB  - OBJECTIVE: The current study aimed at comparison of retention rates for daily
      dispensing (DD) and alternate-day dispensing (AD) regimens for buprenorphine over
      a 1-year period at a tertiary care treatment center for management of substance
      use disorders. Additionally, it aimed at comparison of prescription refill
      proportions for these two buprenorphine dispensing regimens over a 1-year period.
      SETTING: The study was conducted at a tertiary level substance use disorder
      treatment center. PATIENTS, PARTICIPANTS: Case records of patients satisfying the
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria
      for opioid dependence syndrome were included in the study. MAIN OUTCOME MEASURES:
      Retention rates and prescription refill proportions were compared for the two
      buprenorphine dispensing regimens for different time intervals over a 52-week
      period. RESULTS: Fifty-two subjects (45.61 percent) were started on DD regimen
      and 62 (54.38 percent) were put on AD regimen of buprenorphine. All subjects were
      opioid dependent. The two groups did not differ for prescription refill
      proportions as well as retention rates for any of the time intervals studied.
      CONCLUSION: The findings of the current study support feasibility and acceptance
      of alternate-day dosing strategy for buprenorphine dispensing for patients with
      opioid dependence.

PMID- 24944071
TI  - A review of rapid-onset opioids for breakthrough pain in patients with cancer.
AB  - Pain management in patients with cancer remains suboptimal. Breakthrough pain
      (BTP) is characterized by abrupt onset of severe pain in a background of
      otherwise stable managed pain and presents a substantial burden to patients, as
      it disrupts activities and quality of life. Rapid-onset opioids (ROOs), with an
      appropriate onset and duration of effect, provide new options for effective and
      well-tolerated management of BTP. All currently available ROOs are various
      formulations of transmucosal immediate-release fentanyl (TIRF) and, although they
      were originally developed and approved for use in children before painful
      procedures, are only approved for use in opioid-tolerant adult patients with
      cancer and BTP. The formulation options include oral lozenge, buccal tablet,
      buccal film, sublingual tablet, nasal spray, and a sublingual spray; each has
      practical considerations that vary with the product and route of administration.
      All have the common advantage of rapid entry into the systemic circulation via
      transmucosal absorption, avoiding hepatic and intestinal first-pass metabolism
      and allowing a rapid onset of action that rivals intravenous injections. Rapid
      onset and short duration of action allow good patient control of analgesia. The
      pharmacokinetic and analgesic properties of ROOs may allow reduction of the total
      opioid burden and associated adverse effects, while still providing effective
      pain relief. The shared TIRF risk evaluation and mitigation strategy program
      implemented in March 2012 has simplified enrollment and administration of these
      products to help mitigate the risks of abuse and misuse and to help ensure safe
      use in patients with cancer suffering from BTP. 

PMID- 24944072
TI  - Mechanical and hydrodynamic homecare devices to clean rough implant surfaces - an
      in vitro polyspecies biofilm study.
AB  - OBJECTIVES: To investigate the cleaning efficacy of a mechanical and a
      hydrodynamic homecare device on biofilm-coated titanium surfaces with and without
      chlorhexidine. MATERIAL AND METHODS: Six-species biofilms were grown on 108 SLA
      titanium discs, which were cleaned as follows: sonic toothbrush alone (i) or in
      combination with either a 0.2% chlorhexidine (ii) or a placebo gel (iii) and oral
      irrigator (hydrodynamic action) with water (iv) or combined with 0.2%
      chlorhexidine solution (v). Untreated samples served as control (vi). Biofilms
      were then harvested either immediately after treatment (study part A) or after a
      regrowth phase of 24 h (study part B) and colony-forming units (CFU) were
      assessed. Results were analysed using Whitney U-tests between the treatment
      groups. After the Bonferroni correction, the significance level was set at alpha
      = 0.0033. RESULTS: The median CFU counts directly after instrumentation accounted
      - in ascending order (P-values in comparison with the control group A6 were
      <0.001 for all groups except for A3: P = 0.014) - 2.0E1 (A5), 1.1E5 (A4), 3.6E5
      (A2), 3.3E5 (A1) and 6.8E6 (A3), respectively. The untreated control group showed
      the highest CFU counts: 1.8E7 (A6). After regrowth, the following CFU counts were
      measured in ascending order (all P-values <0.001 when compared to the control
      group B6 = 2.0E8): 1.6E2 (B5), 1.9E5 (B2), 1.4E7 (B4), 3.1E7 (B1) and 3.9E7 (B3).
      CONCLUSIONS: An oral irrigator combined with 0.2% chlorhexidine is effective in
      reducing biofilms attached to rough titanium surfaces immediately after cleaning.
      Following a regrowth phase of 24 h, micro-organisms could be equally effective
      removed with a sonic toothbrush combined with 0.2% chlorhexidine and an oral
      irrigator with 0.2% chlorhexidine.

PMID- 24944073
TI  - Detecting protein complexes in protein interaction networks using a ranking
      algorithm with a refined merging procedure.
AB  - BACKGROUND: Developing suitable methods for the identification of protein
      complexes remains an active research area. It is important since it allows better
      understanding of cellular functions as well as malfunctions and it consequently
      leads to producing more effective cures for diseases. In this context, various
      computational approaches were introduced to complement high-throughput
      experimental methods which typically involve large datasets, are expensive in
      terms of time and cost, and are usually subject to spurious interactions.
      RESULTS: In this paper, we propose ProRank+, a method which detects protein
      complexes in protein interaction networks. The presented approach is mainly based
      on a ranking algorithm which sorts proteins according to their importance in the
      interaction network, and a merging procedure which refines the detected complexes
      in terms of their protein members. ProRank + was compared to several state-of-the
      art approaches in order to show its effectiveness. It was able to detect more
      protein complexes with higher quality scores. CONCLUSIONS: The experimental
      results achieved by ProRank + show its ability to detect protein complexes in
      protein interaction networks. Eventually, the method could potentially identify
      previously-undiscovered protein complexes.The datasets and source codes are
      freely available for academic purposes at
      http://faculty.uaeu.ac.ae/nzaki/Research.htm.

PMID- 24944074
TI  - Genotypic characterization and historical perspective of Mycobacterium
      tuberculosis among older and younger Finns, 2008-2011.
AB  - The Mycobacterium tuberculosis genotypes obtained from elderly Finns were
      assessed and compared with those obtained from younger Finns to comprehend the
      epidemiology of tuberculosis (TB) in Finland. From 2008 to 2011, a total of 1021
      M. tuberculosis isolates were characterized by spoligotyping and 15-locus
      mycobacterial interspersed repetitive units-variable number tandem repeat typing.
      In total, 733 Finnish-born cases were included in the study, of which 466 (64%)
      were born before 1945 (older Finns). Of these, 63 (14%) shared an M. tuberculosis
      genotype with foreign-born or younger Finnish cases (born after 1945), and 59
      (13%) shared a genotype with older Finnish cases. Eighty-five per cent had a
      unique genotypic profile while 70% belonged to T or Haarlem families, suggesting
      that ongoing transmission is infrequent among young and elderly Finns.
      Simultaneous reactivation of TB among older Finns was the most likely cause for
      clustering. As most isolates belonged to Haarlem or T, Finland was most likely
      affected by a similar TB epidemic at the beginning of the twentieth century as
      that seen in Sweden and Norway. Younger Finns were significantly more likely to
      be clustered (56% versus 27%, p<0.001), have pulmonary TB (87% versus 71%,
      p<0.001) and to be sputum smear positive (57% versus 48%, p<0.05) indicating that
      the risk of TB transmission from younger Finns is likely to be larger than from
      older Finns. The M. tuberculosis isolates from elderly Finns were associated with
      dominant lineages of the early twentieth century and differed from the
      heterogeneous lineages found among younger TB patients. Additionally, younger TB
      patients were more likely to transmit TB than elderly Finns.

PMID- 24944075
TI  - The efficacy and tolerability of SSRI/SNRIs in the treatment of vasomotor
      symptoms in menopausal women: a systematic review.
AB  - PURPOSE: To systematically review the evidence related to the efficacy and
      tolerability of selective serotonin reuptake inhibitors (SSRIs) and
      serotonin/norepinephrine reuptake inhibitors (SNRIs) used for the treatment of
      vasomotor symptoms in perimenopausal and postmenopausal women. DATA SOURCES:
      Medline, CINAHL, and the Cochrane Library databases were searched to identify
      randomized controlled trials (RCTs). Eighteen trials met the criteria for review.
      CONCLUSIONS: Results from these trials indicate that paroxetine, citalopram,
      escitalopram, venlafaxine, and desvenlafaxine are effective in reducing the
      frequency and severity of hot flashes. Fluoxetine and sertraline appear to be
      less effective and should be considered second-line options for treatment.
      IMPLICATIONS FOR PRACTICE: The SSRIs and SNRIs can reduce hot flashes by 65% and
      begin working within the first week. Patient response is variable and if one drug
      does not improve hot flashes, another can be tried after a 1- to 2-week drug
      trial. Paroxetine, citalopram, and escitalopram appear to have the fewest adverse
      effects. Considering cost, paroxetine and citalopram are the most cost-efficient.

PMID- 24944076
TI  - The anti-tumor efficiency of pterostilbene is promoted with a combined treatment
      of Fas signaling or autophagy inhibitors in triple negative breast cancer cells.
AB  - High expression of vimentin, a canonical mesenchymal marker, is linked with poor
      prognosis in triple negative breast cancer (TNBC), implying that vimentin may be
      a potential biomarker in the application of TNBC therapy. Pterostilbene (PTE) has
      shown anti-invasion activity, and thus, we investigated whether PTE inhibited the
      epithelial-mesenchymal transition (EMT) in TNBC. Here, we show that PTE decreases
      the vimentin expression, but that the effect was transient. PTE stimulated Fas
      signaling, which drives EMT by the ERK1/2 and GSK3beta/beta-catenin pathways,
      supporting Fas signaling induction involved in EMT regulation. PTE also triggered
      autophagy in TNBC. The treatment of TNBC with 3-methyladenine an autophagy
      inhibitor, not only sustained PTE-inhibited EMT but also significantly promoted
      anti-proliferation, which indicates that autophagy plays a cyto-protective role
      and is associated with EMT. Taken together, these data showed that Fas signaling
      and autophagy accelerated the aggressiveness of TNBC. Inhibition of autophagy or
      Fas signaling may provide novel targets for TNBC therapy. 

PMID- 24944077
TI  - Emerging strategies to overcome resistance to endocrine therapy for breast
      cancer.
AB  - Endocrine therapy of breast cancer is perhaps the oldest form of effective and
      well-tolerated targeted cancer systemic treatment, in both the adjuvant and
      metastatic disease settings. The most commonly used endocrine therapy agents are
      selective estrogen receptor modulators, aromatase inhibitors, and selective
      estrogen receptor downregulators. De novo or acquired resistance to these agents
      is a significant clinical problem. Preclinical and clinical investigations to
      understand this resistance have yielded significant advances in understanding
      cell signaling and the possible mechanisms of resistance. These mechanisms of
      resistance are as diverse as the biology of breast cancer and can arise from
      alterations in any of the cell signaling pathway components. A growing
      understanding of these mechanisms has provided rationale for development of
      strategies to overcome the resistance. Many of these mechanisms of resistance
      involve adaptive upregulation of alternate signaling pathways, such as growth
      factor signaling, and cross talk between estrogen receptor and growth factor
      signaling. Clinical trials are focusing on cotargeting these alternate pathways
      along with estrogen receptor signaling. It is becoming evident that, as with all
      cancer therapy, strategies to overcome resistance need to be individualized, and
      it is important to identify biomarkers to guide the use of these strategies. This
      manuscript systemically reviews the recent preclinical and clinical trials on the
      novel and pathway-driven agents that have shown significant promise in enhancing
      the efficacy and overcoming the resistance in the hormonal treatment of breast
      cancer. Future directions including biomarker selection and the role of next
      generation sequencing will be discussed. 

PMID- 24944078
TI  - Androgen receptor enhances cell adhesion and decreases cell migration via
      modulating beta1-integrin-AKT signaling in hepatocellular carcinoma cells.
AB  - The androgen receptor (AR) has been shown to promote the initiation and
      development of hepatocellular carcinoma (HCC) during the early stage of the
      disease process and to suppress HCC cell invasion during the later stages of the
      disease. The mechanisms governing these dual yet opposite roles have yet to be
      elucidated. Using carcinogen-induced HCC in vivo mouse models and the in vitro
      human HCC cell line SKhep1, we found that knockout of AR in primary HCC cells led
      to a decrease in HCC cell focal adhesion capacity compared to cells from wildtype
      mice. Similar results were obtained after adding functional AR into human HCC
      SKhep1 cells. Further analysis revealed that the role AR plays in adhesion of HCC
      cells is governed, at least in part, by its ability to up-regulate beta1-integrin
      and activate the PI3K/AKT pathway. We also found that AR-beta1-integrin-mediated
      cell adhesion suppresses cell migration. Those findings indicate that the AR
      beta1-integrin-PI3K/AKT signaling pathway might play a role in the bimodal
      function of AR on cell adhesion and migration at the cellular level. 

PMID- 24944079
TI  - Factors determining pbsc mobilization efficiency and nonmobilization following
      ICE with or without rituximab (R-ICE) salvage therapy for refractory or relapsed
      lymphoma prior to autologous transplantation.
AB  - ICE/R-ICE (ifosfamide, carboplatin, and etoposide without or with rituximab)
      chemotherapy followed by autologous stem cell transplantation is an established
      regimen in refractory/relapsed lymphoma. Few studies have addressed which factors
      are important in determining peripheral blood stem cell (PBSC) mobilization
      efficiency or nonmobilization following ICE/R-ICE. Between 2004 and 2013, 88
      patients with refractory/relapsed lymphoma who received ICE/R-ICE salvage
      chemotherapy prior to granulocyte colony stimulating factor (G-CSF) stimulated
      PBSC mobilization at a single center were identified. Mobilization efficiency was
      assessed by time from ICE/R-ICE to day of harvest, duration of G-CSF use, days to
      peripheral blood (PB) CD34(+) >=15/uL, PB CD34(+) number on harvest day, CD34(+)
      yield and nonmobilization rate. Median PB CD34(+) at harvest were 54/MUL (7-524);
      median days to first apheresis was 15 (11-30); median harvested total CD34(+)
      were 5.46 * 10(6) /kg (0.96-44.36); 71 patients (80.7%) successfully mobilized;
      20 (22.7%) patients were poor mobilizers; 14 (15.9%) patients were considered
      nonmobilizers with maximal PB CD34(+) <7/uL and did not proceed to apheresis. Six
      of 20 poor mobilizers were apheresed with PB CD34(+) 7-12/uL, 50% were
      successfully harvested. No differences were found between ICE and R-ICE regimens.
      Impaired mobilization efficiency was associated with age, remission status, >1
      line of induction chemotherapy, four cycles ICE/R-ICE and grade 4 neutropenia.
      Prior bone marrow (BM) involvement was associated with nonmobilization. The
      majority of patients can be successfully mobilized with ICE/R-ICE. Prior BM
      involvement is associated with high rates of nonmobilization following ICE/R-ICE.
      Such patients may benefit from novel mobilization agents and/or alternative
      salvage regimens to ICE/R-ICE.

PMID- 24944080
TI  - Molecular typing of avian pathogenic Escherichia coli colonies originating from
      outbreaks of E. coli peritonitis syndrome in chicken flocks.
AB  - Escherichia coli colonies isolated from the bone marrow of fresh dead hens of
      laying flocks with the E. coli peritonitis syndrome (EPS) were genotyped using
      pulsed-field gel electrophoresis (PFGE). Typing is important from an
      epidemiological point of view and also if the use of autogenous (auto)vaccines is
      considered. Birds with EPS originated from one house of each of three layer farms
      and one broiler breeder farm. Farms were considered as separate epidemiological
      units. In total, six flocks were examined including two successive flocks of one
      layer farm and the broiler breeder farm. E. coli colonies (one per bird) from
      nine to 16 hens of each flock were genotyped. The clonality of E. coli within
      birds was studied using five colonies of each of nine to 14 birds per flock. E.
      coli genotypes, which totalled 15, differed between farms and flocks except for
      two successive layer flocks that shared three genotypes. One to five genotypes
      were found per flock with one or two genotypes dominating each outbreak. Within
      hens, E. coli bacteria were always clonal. Colonies of the same PFGE type always
      had the same multilocus sequence type. However, four PFGE types shared sequence
      type 95. Neither PFGE types nor multilocus sequence types were unambiguously
      related to avian pathogenic E. coli from EPS. In cases where persistence of E.
      coli strains associated with EPS is found to occur frequently, routine genotyping
      to select strains for autovaccines should be considered. 

PMID- 24944081
TI  - Near constant loss regime in fast ionic conductors analyzed by impedance and NMR
      spectroscopies.
AB  - Universal dielectric response (UDR) and nearly constant loss (NCL) dispersive
      regimes have been investigated in fast ion conductors with perovskite and NASICON
      structure by using NMR and impedance spectroscopy (IS). In this study, the
      electrical behavior of La(0.5)Li(0.5)TiO3 (LLTO-05) perovskite and
      Li(1.2)Ti(1.8)Al(0.2)(PO4)3 (LTAP0-02) NASICON compounds was investigated. In
      both systems a three-dimensional network of conduction paths is present. In the
      Li-rich LLTO-05 sample, lithium and La are randomly distributed on A-sites of
      perovskites, but in LTAP0-02 Li and cation vacancies are preferentially disposed
      at M1 and M2 sites. In perovskite compounds, local motions produced inside unit
      cells are responsible for the large "near constant loss" regime detected at low
      temperatures, however, in the case of NASICON compounds, local motions not
      participating in long-range charge transport were not detected. In both analyzed
      systems long-range correlated motions are responsible for dc-conductivity values
      of ceramic grains near 10(-3) S cm(-1) at room temperature, indicating that low
      temperature local motions, producing large NCL contribution, are not required to
      achieve the highest ionic conductivities.

PMID- 24944083
TI  - Identification of human cytochrome P450 isozymes involved in the metabolism of
      naftopidil enantiomers in vitro.
AB  - OBJECTIVES: Naftopidil (NAF) is a chiral compound with two enantiomers (R(+)-NAF
      and S(-)-NAF) and is used as a racemic mixture in clinical practice. This study
      aims to investigate the metabolism of NAF enantiomers in pooled human liver
      microsomes (HLMs) and cytochrome P450 isozymes (CYPs) involved in their
      metabolism. METHODS: Metabolism studies were conducted in vitro using HLMs.
      Specific chemical inhibitors and recombinant human CYPs were used to confirm that
      the CYPs contributed to the metabolism of NAF enantiomers. KEY FINDINGS: Three
      metabolites were found and characterized in the HLMs incubations from R(+)-NAF
      and S(-)-NAF, respectively. The major metabolic pathways of R(+)-NAF and S(-)-NAF
      were demethylation and hydroxylation. CYP2C9 and CYP2C19 inhibitors strongly
      inhibited R(+)-NAF metabolism, and CYP1A2, CYP2C8, CYP2D6 and CYP3A4/5 inhibitors
      moderately inhibited R(+)-NAF metabolism. CYP2C9 inhibitors strongly inhibited S(
      )-NAF metabolism, and CYP2C8, CYP2C19 and CYP3A4/5 inhibitors moderately
      inhibited S(-)-NAF metabolism. Consistent with the results of chemical inhibitors
      experiments, recombinant human CYP2C9 and CYP2C19 contributed greatly to R(+)-NAF
      metabolism, and CYP2C9 contributed greatly to S(-)-NAF metabolism. CONCLUSION:
      Both R(+)-NAF and S(-)-NAF are metabolized to three metabolites in HLMs. CYP2C9
      plays the most important role in the demethylation and hydroxylation of both NAF
      enantiomers, CYP2C19 is another major CYP isoform that is involved in R(+)-NAF
      metabolism.

PMID- 24944082
TI  - Specific binding of lacosamide to collapsin response mediator protein 2 (CRMP2)
      and direct impairment of its canonical function: implications for the therapeutic
      potential of lacosamide.
AB  - The novel antiepileptic drug lacosamide (LCM; SPM927, Vimpat(r)) has been
      heralded as having a dual-mode of action through interactions with both the
      voltage-gated sodium channel and the neurite outgrowth-promoting collapsin
      response mediator protein 2 (CRMP2). Lacosamide's ability to dampen neuronal
      excitability through the voltage-gated sodium channel likely underlies its
      efficacy in attenuating the symptoms of epilepsy (i.e., seizures). While the role
      of CRMP2 in epilepsy has not been well studied, given the proposed involvement of
      circuit reorganization in epileptogenesis, the ability of lacosamide to alter
      CRMP2 function may prove disease modifying. Recently, however, the validity of
      lacosamide's interaction with CRMP2 has come under scrutiny. In this review, we
      address the contradictory reports concerning the binding of lacosamide to CRMP2
      as well as the ability of lacosamide to directly impact CRMP2 function.
      Additionally, we address similarly the contradicting reports regarding the
      potential disease-modifying effect of lacosamide on the development and
      progression of epilepsy. As the vast majority of antiepileptic drugs influences
      only the symptoms of epilepsy, the ability to hinder disease progression would be
      a major breakthrough in efforts to cure or prevent this debilitating syndrome.

PMID- 24944084
TI  - The NMDAr antagonist ketamine interferes with manipulation of information for
      transitive inference reasoning in non-human primates.
AB  - One of the most remarkable traits of highly encephalized animals is their ability
      to manipulate knowledge flexibly to infer logical relationships. Operationally,
      the corresponding cognitive process can be defined as reasoning. One hypothesis
      is that this process relies on the reverberating activity of glutamate neural
      circuits, sustained by NMDA receptor (NMDAr) mediated synaptic transmission, in
      both parietal and prefrontal areas. We trained two macaque monkeys to perform a
      form of deductive reasoning - the transitive inference task - in which they were
      required to learn the relationship between six adjacent items in a single session
      and then deduct the relationship between nonadjacent items that had not been
      paired in the learning phase. When the animals had learned the sequence, we
      administered systemically a subanaesthetic dose of ketamine (a NMDAr antagonist)
      and measured their performance on learned and novel problems. We observed
      impairments in determining the relationship between novel pairs of items. Our
      results are consistent with the hypothesis that transitive inference premises are
      integrated during learning in a unified representation and that reducing NMDAr
      activity interferes with the use of this mental model, when decisions are
      required in comparing pairs of items that have not been learned. 

PMID- 24944085
TI  - Anion channel SLAH3 functions in nitrate-dependent alleviation of ammonium
      toxicity in Arabidopsis.
AB  - Slow anion channels (SLAC/SLAH) are efflux channels previously shown to be
      critical for stomatal regulation. However, detailed analysis using the beta
      glucuronidase reporter gene showed that members of the SLAC/SLAH gene family are
      predominantly expressed in roots, in addition to stomatal guard cells,
      implicating distinct function(s) of SLAC/SLAH in the roots. Comprehensive mutant
      analyses of all slac/slah mutants indicated that slah3 plants showed a greater
      growth defect than wild-type plants when ammonium was supplied as the sole
      nitrogen source. Ammonium toxicity was mimicked by acidic pH in nitrogen-free
      external medium, suggesting that medium acidification by ammonium-fed plants may
      underlie ammonium toxicity. Interestingly, such toxicity was more severe in slah3
      mutants and, particularly in wild-type plants, was alleviated by supplementing
      the media with micromolar levels of nitrate. These data thus provide evidence
      that SLAH3, a nitrate efflux channel, plays a role in nitrate-dependent
      alleviation of ammonium toxicity in plants. 

PMID- 24944086
TI  - The usefulness of ultrasound in anaesthesia.

PMID- 24944087
TI  - Religious Attendance, Health-Promoting Lifestyle Behaviors, and Depressive
      Symptoms Among Koreans in the United Arab Emirates (UAE).
AB  - Migrants, who comprise 80 % of the population in the United Arab Emirates, are at
      risk of developing mental health disorders. To test associations among religious
      attendance, health-promoting lifestyle behaviors (HPLB), and depressive symptoms,
      we conducted a cross-sectional survey in Dubai. Measures included frequency of
      religious attendance, the Health-Promoting Lifestyle Profile, and the Depression,
      Anxiety, and Stress Scale. Multiple regression analyses were used to explore
      relationships among religious attendance, HPLB, and depressive symptoms.
      Religious attendance was significantly associated with self-actualization, stress
      management, and depressive symptoms. Self-actualization and stress management
      mediated the relationships between religious attendance and depressive symptoms
      for both males and females, and interpersonal support mediated the relationship
      for females, controlling for age and education. The facilitation of positive
      internal and external resources generated by participating in religious
      activities may have increased the likelihood that the Korean migrants would
      engage in psychosocial healthy lifestyle behaviors, and may have decreased
      depressive symptoms. 

PMID- 24944089
TI  - Sudden infant death syndrome.

PMID- 24944090
TI  - Natural bond orbital/natural J-coupling study of vicinal couplings.
AB  - NBO-NJC decomposition of vicinal (3)J HH spin-spin coupling constants into Lewis,
      delocalization, and repolarization contributions are presented. A deep study
      allows to assign the main contributions to specific orbitals or electron
      delocalizations between two orbitals. (3)J HH torsional dependence and the
      substituent effect are analyzed according to the main orbital contributions for
      ethane and fluoroethane molecules using different basis sets. The torsional
      dependence for the energies corresponding to electron delocalization is also
      studied.

PMID- 24944088
TI  - Adolescent chronic fatigue syndrome and somatoform disorders: a prospective
      clinical study.
AB  - AIM: To examine and compare the presenting characteristics and the change in the
      physical and psychosocial functioning of adolescents with chronic fatigue
      syndrome (CFS) or somatoform disorders who have received an adaptable
      multidisciplinary intervention over a 12-month period. METHODS: Fifty adolescents
      presenting to the Complex Adolescent Clinic at The Children's Hospital at
      Westmead, Sydney, Australia were assessed. Their physical and psychosocial
      functioning was rated by the adolescents and their parents using the Child Health
      Questionnaire. Participants were assessed at baseline, 4 months and 12 months
      after initiating treatment. Analyses examined whether diagnosis and/or illness
      precipitants were related to treatment outcome. RESULTS: Adolescents with both
      CFS and somatoform disorders demonstrated improvement in physical and
      psychosocial functioning over the first 4 months of treatment, sustained at 12
      month follow-up. A diagnosis of CFS was associated with poorer physical
      functioning over time and a trend towards a longer illness time course compared
      with somatoform disorder. Adjustment for a physical precipitant reduced the
      association between diagnosis and physical functioning. Those who had a physical
      precipitant to their illness had significantly poorer physical functioning over
      time than those who did not, regardless of diagnostic category. Diagnosis and
      physical precipitant were not associated with psychosocial functioning.
      CONCLUSIONS: Improvement in adolescent physical and psychosocial functioning over
      time suggests that a multidisciplinary treatment model may be effective for
      varied complex medico-psychosocial presentations, irrespective of diagnosis and
      illness precipitant. Illness precipitant may have a greater influence on
      treatment outcome than diagnostic category.

PMID- 24944091
TI  - Modeling bacterial quorum sensing in open and closed environments: potential
      discrepancies between agar plate and culture flask experiments.
AB  - Quorum sensing (QS) is a process of bacterial communication and cooperation
      mediated by the release of jointly exploited signals and "public goods" into the
      environment. There are conflicting reports on the behavior of mutants deficient
      in the release of these materials. Namely, mutants that appear perfectly viable
      and capable of outgrowing wild type cells in a closed model system such as a
      culture flask, may not be viable or invasive on open surfaces such as agar
      plates. Here we show via agent-based computational simulations that this apparent
      discrepancy is due to the difference between open and closed systems. We suggest
      that the experimental difference is due to the fact that wild type cells can
      easily saturate a well-mixed culture flask with signals and public goods so QS
      will be not necessary after a certain time point. As a consequence, QS-deficient
      mutants can continue to grow even after the wild type population has vanished.
      This phenomenon is not likely to occur in open environments including open
      surfaces and agar plate models. In other words, even if QS is required for
      survival, QS deficient mutants may grow faster initially in short term laboratory
      experiments or computer simulations, while only WT cells appear stable over
      longer time scales, especially when adaptation to changing environments is
      important. 

PMID- 24944092
TI  - Structural and electronic study of neutral, positive, and negative small rhodium
      clusters [Rh(n), Rh(n)(+), Rh(n)(-) ; n = 10-13].
AB  - We have carried out a systematic study for the determination of the structure and
      the fundamental state of neutral and ionic small rhodium clusters [Rhn, Rhn(+),
      Rhn(-); n = 10-13] using ab initio Hartree-Fock methods with a LANL2DZ basis set.
      A range of spin multiplicities is investigated for each cluster. We present the
      bond lengths, angles, and geometric configuration adopted by the clusters in its
      minimum energy conformation showing the differences when the clusters have
      different number of unpaired electrons. Also we report the vertical ionization
      potential and the adiabatic one calculated by the Koopmans' theorem.

PMID- 24944093
TI  - Computational study of interactions and nuclear magnetic shielding constants in
      linear chains of formamide clusters.
AB  - We investigated the energetic, structural, dielectric, and nuclear magnetic
      shielding properties of linear n-formamide clusters, with n up to 6, to
      quantitatively characterize cooperative effects in model biological systems. The
      geometries of the complexes were optimized at the MP2 and DFT/B3LYP levels by
      using the pc-2 and pc-3 basis sets, while the nuclear magnetic shielding
      constants were calculated by employing pcS-n type basis sets, which have been
      optimized specifically for density functional calculations of these properties.
      The interaction energies show the cooperative effect, which favors the successive
      addition of monomers. In addition, by analyzing structural changes in the
      intermolecular C=O, C-N and hydrogen O?H bonds, as well as in the average dipole
      moments as cluster size increases, we found that the cooperative interaction far
      exceeds that expected for electrostatic interactions. Such non-pairwise-additive
      effects are also reflected in the changes of the nuclear magnetic shielding
      constants. In particular, the negativity of O shielding decreases around 23% from
      the monomer to the 6-formamide chain. It is possible to note the decrease in the
      shielding of H and in the deshielding of O as a result of their hydrogen bonding.
      However, the results obtained show that these variations in the extremes of
      formamide chains tend to zero, and the respective shielding values tend to
      stabilize as the number of monomers increases in the chain. Also, the cooperative
      effect increases in the middle of the chains, by decreasing the shielding for all
      atoms except that of O, which decreases its deshielding. These results could
      serve to guide improvements in current conventional models for simulating
      hydrogen bonded systems.

PMID- 24944094
TI  - EMPIRE: a highly parallel semiempirical molecular orbital program: 1: self
      consistent field calculations.

PMID- 24944095
TI  - Core-valence correlation effects on IR calculations: the BF3 and BCl3 cases.
AB  - The first theoretical results of core-valence correlation effects are presented
      for the infrared wavenumbers and intensities of the BF3 and BCl3 molecules, using
      (double- and triple-zeta) Dunning core-valence basis sets at the CCSD(T) level.
      The results are compared with those calculated in the frozen core approximation
      with standard Dunning basis sets at the same correlation level and with the
      experimental values. The general conclusion is that the effect of core-valence
      correlation is, for infrared wavenumbers and intensities, smaller than the effect
      of adding augmented diffuse functions to the basis set, e.g., cc-pVTZ to aug-cc
      pVTZ. Moreover, the trends observed in the data are mainly related to the
      augmented functions rather than the core-valence functions added to the basis
      set. The results obtained here confirm previous studies pointing out the large
      descrepancy between the theoretical and experimental intensities of the
      stretching mode for BCl3. 

PMID- 24944096
TI  - Ionic liquid-based dispersive liquid-liquid microextraction followed by RP-HPLC
      determination of saquinavir in rat serum: application to pharmacokinetics.
AB  - An ionic liquid-based dispersive liquid-liquid microextraction followed by RP
      HPLC determination of the most commonly prescribed protease inhibitor,
      saquinavir, in rat plasma was developed and validated. The effects of different
      ionic liquids, dispersive solvents, extractant/disperser ratio and salt
      concentration on sample recovery and enrichment were studied. Among the ionic
      liquids investigated, 1-butyl-3-methylimidazolium hexafluorophosphate was found
      to be most effective for extraction of saquinavir from rat serum. The recovery
      was found to be 95% at an extractant/disperser ratio of 0.43 using 1-butyl-3
      methylimidazolium hexafluorophosphate and methanol as extraction and dispersive
      solvents. The recovery was further enhanced to 99.5% by addition of 5.0% NaCl. A
      threefold enhancement in detection and quantification limits was achieved, at
      0.01 and 0.03 ug/mL, compared with the conventional protein precipitation method.
      A linear relationship was observed in the range of 0.035-10.0 ug/mL with a
      correlation coefficient (r(2) ) of 0.9996. The method was validated and applied
      to study pharmacokinetics of saquinavir in rat serum.

PMID- 24944097
TI  - Transcriptional regulation of podoplanin expression by Prox1 in lymphatic
      endothelial cells.
AB  - Transcription factor prospero homeobox 1 (Prox-1) and podoplanin (PDPN), mucin
      type transmembane protein, are both constantly expressed in lymphatic endothelial
      cells (LECs) and appear to function in an LEC-autonomous manner. Mice globally
      lacking PDPN (Pdpn(-/-)) develop abnormal and blood-filled lymphatic vessels that
      highly resemble those in inducible mice lacking Prox-1 (Prox1(-/-)). Prox1 has
      also been reported to induce PDPN expression in cultured ECs. Thus, we
      hypothesize that PDPN functions downstream of Prox1 and that its expression is
      regulated by Prox1 in LECs at the transcriptional level. We first identified four
      putative binding elements for Prox1 in the 5' upstream regulatory region of Pdpn
      gene and found that Prox1 directly binds to the 5' regulatory sequence of Pdpn
      gene in LECs by chromatin immunoprecipitation assay. DNA pull down assay
      confirmed that Prox1 binds to the putative binding element. In addition,
      luciferase reporter assay indicated that Prox1 binding to the 5' regulatory
      sequence of Pdpn regulates Pdpn gene expression. We are therefore the first to
      experimentally demonstrate that Prox1 regulates PDPN expression at the
      transcriptional level in the lymphatic vascular system. 

PMID- 24944098
TI  - Practical fluorescence detection of acrolein in human plasma via a two-step
      tethering approach.
AB  - Acrolein, a cytotoxic alpha,beta-unsaturated aldehyde and disease biomarker, was
      determined in plasma by means of a novel tethering strategy using Michael
      addition of the compound to a fluorescent dye, followed by immobilization of the
      product on microbeads via the aldehyde moiety. Elevation of blood acrolein was
      detected in mice treated with an anticancer agent cyclophosphamide, which
      releases acrolein upon activation. This method should be suitable for high
      throughput diagnostic and clinical application. 

PMID- 24944099
TI  - Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive
      mutational spectrum and highlights missense hotspots.
AB  - Alterations of USH2A, encoding usherin, are responsible for more than 70% of
      cases of Usher syndrome type II (USH2), a recessive disorder that combines
      moderate to severe hearing loss and retinal degeneration. The longest USH2A
      transcript encodes usherin isoform b, a 5,202-amino-acid transmembrane protein
      with an exceptionally large extracellular domain consisting notably of a Laminin
      N-terminal domain and numerous Laminin EGF-like (LE) and Fibronectin type III
      (FN3) repeats. Mutations of USH2A are scattered throughout the gene and mostly
      private. Annotating these variants is therefore of major importance to correctly
      assign pathogenicity. We have extensively genotyped a novel cohort of 152 Usher
      patients and identified 158 different mutations, of which 93 are newly described.
      Pooling this new data with the existing pathogenic variants already incorporated
      in USHbases reveals several previously unappreciated features of the mutational
      spectrum. We show that parts of the protein are more likely to tolerate single
      amino acid variations, whereas others constitute pathogenic missense hotspots. We
      have found, in repeated LE and FN3 domains, a nonequal distribution of the
      missense mutations that highlights some crucial positions in usherin with
      possible consequences for the assessment of the pathogenicity of the numerous
      missense variants identified in USH2A. 

PMID- 24944100
TI  - The 100S ribosome: ribosomal hibernation induced by stress.
AB  - One of the most important cellular events in all organisms is protein synthesis
      (translation), which is catalyzed by ribosomes. The regulation of translational
      activity is dependent on the environmental situation of the cell. A decrease in
      overall translation under stress conditions is mainly accompanied by the
      formation of functionally inactive 100S ribosomes in bacteria. The 100S ribosome
      is a dimer of two 70S ribosomes that is formed through interactions between their
      30S subunits. Two mechanisms of 100S ribosome formation are known: one involving
      ribosome modulation factor (RMF) and short hibernation promoting factor (HPF) in
      a part of Gammaproteobacteria including Escherichia coli, and the other involving
      only long HPF in the majority of bacteria. The expression of RMF is regulated by
      ppGpp and cyclic AMP-cAMP receptor protein (cAMP-CRP) induced by amino acid
      starvation and glucose depletion, respectively. When stress conditions are
      removed, the 100S ribosome immediately dissociates into the active 70S ribosomes
      by releasing RMF. The stage in the ribosome cycle at which the ribosome loses
      translational activity is referred to as 'Hibernation'. The lifetime of cells
      that cannot form 100S ribosomes by deletion of the rmf gene is shorter than that
      of parental cells under stress conditions in E. coli. This fact indicates that
      the interconversion system between active 70S ribosomes and inactive 100S
      ribosomes is an important survival strategy for bacteria.

PMID- 24944102
TI  - Effect of particle size on risk assessment of direct soil ingestion and metals
      adhered to children's hands at playgrounds.
AB  - The quantity of heavy metals in soil is measured after 2-mm sieving in Japan for
      risk assessment of direct soil ingestion. A study was conducted on the
      relationship between the size of soil particles and quantity of heavy metals in
      soil, and the particle-size distribution of soil adhered to children's hands, and
      the risks of direct intake of soil considering the particle sizes ingested were
      evaluated. The results showed that smaller particles had a tendency to contain
      more heavy metals than bigger ones, that the particle size of approximately 90%
      of the soil particles from playgrounds adhered to children's hands was less than
      100 MUm, and that 2-mm sieving in preparation for measuring heavy metal content
      caused underestimation of the risk of direct soil intake. The amount of heavy
      metals on children's hands after playing outside was investigated. Various metals
      and soil were adhered to their hands, and the amount of soil adhered could be
      estimated from the concentration of metals. To develop accurate risk assessment,
      the particle-size distribution of ingested soil and more detailed scenarios of
      soil intake are necessary. 

PMID- 24944103
TI  - New insight into the enhanced effect of pegylated interferon-alpha.

PMID- 24944101
TI  - 'Default' generated neonatal regulatory T cells are hypomethylated at conserved
      non-coding sequence 2 and promote long-term cardiac allograft survival.
AB  - Regulatory T (Treg) cells play an important role in the maintenance of immune
      self-tolerance and homeostasis. We previously reported that neonatal CD4(+) T
      cells have an intrinsic 'default' mechanism to become Treg (neoTreg) cells in
      response to T-cell receptor (TCR) stimulation. However, the underlying mechanisms
      are unclear and the effects of neoTreg cells on regulating immune responses
      remain unknown. Due to their involvement in Foxp3 regulation, we examined the
      role of DNA methyltransferase 1 (DNMT1) and DNMT3b during the induction of
      neoTreg cells in the Foxp3(gfp) mice. The function of neoTreg cells was assessed
      in an acute allograft rejection model established in RAG2(-/-) mice with
      allograft cardiac transplantation and transferred with syngeneic CD4(+) effector
      T cells. Following ex vivo TCR stimulation, the DNMT activity was increased
      threefold in adult CD4(+) T cells, but not significantly increased in neonatal
      cells. However, adoptively transferred neoTreg cells significantly prolonged
      cardiac allograft survival (mean survival time 47 days, P < 0.001) and maintained
      Foxp3 expression similar to natural Treg cells. The neoTreg cells were
      hypomethylated at the conserved non-coding DNA sequence 2 locus of Foxp3 compared
      with adult Treg cells. The DNMT antagonist 5-aza-2'-deoxycytidine (5-Aza) induced
      increased Foxp3 expression in mature CD4(+) T cells. 5-Aza-inducible Treg cells
      combined with continuous 5-Aza treatment prolonged graft survival. These results
      indicate that the 'default' pathway of neoTreg cell differentiation is associated
      with reduced DNMT1 and DNMT3b response to TCR stimulus. The neoTreg cells may be
      a strategy to alleviate acute allograft rejection.

PMID- 24944104
TI  - The role of the oculomotor system in covert social attention.
AB  - Observing a change in gaze direction triggers a reflexive shift of attention and
      appears to engage the eye-movement system. However, the functional relationship
      between social attention and this oculomotor activation is unclear. One extremely
      influential hypothesis is that the preparation of a saccadic eye movement is
      necessary and sufficient for a covert, reflexive shift of attention (the premotor
      theory of attention; Rizzolatti et al., 1994). Surprisingly, this theory has not
      been directly tested with respect to reflexive gaze cueing. In order to address
      this issue, gaze cueing, peripheral cueing, and arrow cueing were examined under
      conditions in which some stimuli appeared at locations that could not become the
      goal of a saccadic eye movement. It was observed that peripheral cues failed to
      elicit reflexive attentional orienting when targets appeared beyond the range of
      eye movements. Similarly, nonpredictive arrow cues were ineffective when targets
      could not become the goal of a saccade. In contrast, significant gaze-cueing
      effects were still observed when targets were beyond the range of eye movements.
      These data demonstrate that the mechanisms involved in gaze cueing are
      dissociated from those involved in exogenous orienting to peripheral or arrow
      cues. Furthermore, the findings suggest that, unlike peripheral cueing and
      reflexive arrow cueing, gaze cueing is independent of oculomotor control. We
      conclude that the premotor theory does not offer a compelling explanation for
      gaze cueing. 

PMID- 24944105
TI  - Reward associations and spatial probabilities produce additive effects on
      attentional selection.
AB  - Recent studies have shown that reward history acts as a powerful attentional
      bias, even overcoming top-down goals. This has led to the suggestion that rewards
      belong to a class of attentional cues based on selection history, which are
      defined by past outcomes with a stimulus feature. Selection history is thought to
      be separate from traditional attentional cues based on physical salience and
      voluntary goals, but there is relatively little understanding of how selection
      history operates as a mechanism of attentional selection. Critically, it has yet
      to be understood how multiple sources of selection history interact when
      presented simultaneously. For example, it may be easier to find something we like
      if it also appears in a predictable location. We therefore pitted spatial
      probabilities against reward associations and found that the two sources of
      information had independent and additive effects. Additionally, the strength of
      the two sources in biasing attentional selection could be equated. In contrast,
      while a nonpredictive but perceptually salient cue also exhibited independent and
      additive effects with reward, reward associations dominated the perceptually
      salient cue at all levels. Our data indicate that reward associations are part of
      a class of particularly potent attentional cues that guide behavior through
      learned expectations. However, selection history should not be thought of as a
      unitary concept but should be understood as a collection of independent sources
      of information that bias attention in a similar fashion. 

PMID- 24944106
TI  - Tactile spatial negative priming occurs without feature mismatch.
AB  - Negative priming (NP) refers to fact that people respond more slowly and make
      more errors when responding to target stimuli that were previously ignored. This
      phenomenon has also been observed when participants respond to the location, and
      not only to the identity, of the stimulus. Intriguingly, while roughly the same
      pattern of results has been observed in the visual, auditory, and tactile
      modalities when it comes to identity-based NP, the same does not hold true for
      spatial NP: In particular, feature mismatch seems to be the sole cause of
      auditory spatial NP, whereas response inhibition would appear to be the sole
      cause of spatial NP in vision. We conducted a novel tactile variant of the
      spatial NP task. We investigated whether spatial NP in the tactile modality
      exists, and further, we investigated whether the pattern of spatial NP in the
      tactile modality compares with what has been documented previously in vision or
      audition. Tactile spatial NP was observed, and it was independent of feature
      mismatch, thereby reflecting a comparable pattern as visual spatial NP. We
      discuss spatial selection with respect to possible modality-specific processes. 

PMID- 24944107
TI  - Challenges facing totally endoscopic robotic coronary artery bypass grafting.
AB  - BACKGROUND: Robot-assisted surgery is growing in popularity; however, robotic
      totally endoscopic coronary artery surgery (TECAB) remains challenging,
      particularly in multi-vessel disease. METHODS: A review of the current literature
      surrounding TECAB using the da Vinci(r) system. RESULTS: The da Vinci robot is
      the only commercially available system, operating on a master-slave paradigm with
      the surgeon controlling the robotic arms from a remote console. CONCLUSIONS:
      Robotic surgery today is presented with challenges, including dealing with a non
      perfect robot without haptic control, a steep learning curve, lack of established
      training criteria and high cost. Strategies such as structured, simulated
      training and novel anastomotic devices may potentially shorten the learning
      curve, improve patency and facilitate grafting in multi-vessel disease. Future
      challenges will include the ability to demonstrate long-term patency, morbidity
      and mortality at least comparable to conventional CABG, whilst also offering cost
      effectiveness in this increasingly difficult economic environment.

PMID- 24944109
TI  - Reduced peroxisomal citrate synthase activity increases substrate availability
      for polyhydroxyalkanoate biosynthesis in plant peroxisomes.
AB  - Polyhydroxyalkanoates (PHAs) are bacterial carbon storage polymers used as
      renewable, biodegradable plastics. PHA production in plants may be a way to
      reduce industrial PHA production costs. We recently demonstrated a promising
      level of peroxisomal PHA production in the high biomass crop species sugarcane.
      However, further production strategies are needed to boost PHA accumulation
      closer to commercial targets. Through exogenous fatty acid feeding of Arabidopsis
      thaliana plants that contain peroxisome-targeted PhaA, PhaB and PhaC enzymes from
      Cupriavidus necator, we show here that the availability of substrates derived
      from the beta-oxidation cycle limits peroxisomal polyhydroxybutyrate (PHB)
      biosynthesis. Knockdown of peroxisomal citrate synthase activity using artificial
      microRNA increased PHB production levels approximately threefold. This work
      demonstrates that reduction of peroxisomal citrate synthase activity may be a
      valid metabolic engineering strategy for increasing PHA production in other plant
      species. 

PMID- 24944108
TI  - The effect of metformin on breast cancer outcomes in patients with type 2
      diabetes.
AB  - Observational data suggest that metformin use decreases breast cancer (BC)
      incidence in women with diabetes; the impact of metformin on BC outcomes in this
      population is less clear. The purpose of this analysis was to explore whether
      metformin use influences BC outcomes in women with type 2 diabetes. Prospective
      institutional databases were reviewed to identify patients with diabetes who
      received chemotherapy for stages I-III BC from 2000 to 2005. Patients diagnosed
      with diabetes before or within 6 months of BC diagnosis were included. Males and
      those with type I, gestational, or steroid-induced diabetes were excluded.
      Patients were stratified based on metformin use, at baseline, defined as use at
      time of BC diagnosis or at diabetes diagnosis if within 6 months of BC diagnosis.
      Kaplan-Meier methods were used to estimate rates of recurrence-free survival
      (RFS), overall survival (OS), and contralateral breast cancer (CBC). We
      identified 313 patients with diabetes who received chemotherapy for BC, 141 (45%)
      fulfilled inclusion criteria and 76 (54%) used metformin at baseline. There were
      no differences in clinical presentation or tumor characteristics between
      metformin users and nonusers. At a median follow-up of 87 months (range, 6.9
      140.4 months), there was no difference in RFS (P = 0.61), OS (P = 0.462), or CBC
      (P = 0.156) based on metformin use. Five-year RFS was 90.4% (95% CI, 84-97) in
      metformin users and 85.4% (95% CI, 78-94) in nonusers. In this cohort of patients
      with type 2 diabetes receiving systemic chemotherapy for invasive BC, the use of
      metformin was not associated with improved outcomes.

PMID- 24944110
TI  - Quorum sensing signalling and biofilm formation of brewery-derived bacteria, and
      inhibition of signalling by natural compounds.
AB  - Bacteria use quorum sensing signalling in various functions, e.g. while forming
      biofilms, and inhibition of this signalling could be one way to control biofilm
      formation. The aim of this study was to evaluate the production of signalling
      molecules and its correlation with the biofilm formation capability of bacteria
      isolated from brewery filling process. A further aim was to study berry extracts
      and wood-derived terpenes for their possible quorum sensing inhibitory effects.
      Out of the twenty bacteria studied, five produced short-chain and five long-chain
      AHL (acyl homoserine lactone) signalling molecules when tested with the
      Chromobacterium violaceum CV026 reporter bacterium. Production of AI-2
      (autoinducer-2) signalling molecules was detected from nine strains with the
      Vibrio harveyi BB170 bioassay. Over half of the strains produced biofilm in the
      microtitre plate assay, but the production of AHL and AI-2 signalling molecules
      and biofilm formation capability did not directly correlate with each other. Out
      of the 13 berry extracts and wood-derived terpenes screened, four compounds
      decreased AHL signalling without effect on growth. These were betulin, raspberry
      extract and two cloudberry extracts. The effect of these compounds on biofilm
      formation of the selected six bacterial strains varied. The phenolic extract of
      freeze-dried cloudberry fruit caused a statistically significant reduction of
      biofilm formation of Obesumbacterium proteus strain. Further experiments should
      aim at identifying the active compounds and revealing whether quorum sensing
      inhibition causes structural changes in the biofilms formed. 

PMID- 24944112
TI  - Direct laser writing of 3D architectures of aligned carbon nanotubes.
AB  - Direct laser writing through two-photon polymerization lithography is used to
      fabricate 3D nanostructures containing aligned single-wall carbon nanotubes
      (SWCNTs). SWCNTs are aligned in the laser scanning directions while they are
      embedded in the structure. The alignment is induced by spatial confinement,
      volume shrinkage, and the optical gradient force. This method is expected to lead
      to new applications based on aligned SWCNTs. 

PMID- 24944111
TI  - Characterization of a lily anther-specific gene encoding cytoskeleton-binding
      glycoproteins and overexpression of the gene causes severe inhibition of pollen
      tube growth.
AB  - This work characterizes an anther/pollen-specific gene that encodes potential
      intermediate filament (IF)-binding glycoproteins in lily (Lilium longiflorum
      Thunb. cv. Snow Queen) anthers during the development and pollen germination.
      LLP13 is a single gene that encodes a polypeptide of 807 amino acids, and a
      calculated molecular mass of 91 kDa. The protein contains a predicted
      transmembrane domain at the N-terminus and a conserved domain of unknown function
      (DUF)593 at the C-terminal half of the polypeptide. Sequence analysis revealed
      that LLP13 shares significant identity (37-41 %) with two intermediate filament
      antigen-binding proteins, representing a unique subgroup of DUF593 domain
      proteins from known rice and Arabidopsis species. The expression of LLP13 gene is
      anther-specific, and the transcript accumulates only at the stage of pollen
      maturation. Both premature drying and abscisic acid (ABA) treatment of developing
      pollen indicated that LLP13 was not induced by desiccation and ABA, but by other
      developmental cues. Antiserum was raised against the overexpressed LLP13C
      fragment of the protein in Escherichia coli and affinity-purified antibodies were
      prepared. Immunoblot analyses revealed that the LLP13 protein was a
      heterogeneous, anther-specific glycoprotein that accumulated only at the stage of
      pollen maturation. The protein is not heat-soluble. The level of LLP13 protein
      remained for 24 h during germination in vitro. Overexpression of LLP13-GFP or GFP
      LLP13 in lily pollen tubes caused severe inhibition of tube elongation. The LLP13
      protein codistributed with mTalin in growing tubes, suggesting that it apparently
      decorates actin cytoskeleton and is likely a cytoskeleton-binding protein that
      binds with IFs that potentially exist in pollen tubes.

PMID- 24944113
TI  - Mechanisms and methods in ecoimmunology: integrating within-organism and between
      organism processes.
AB  - Ecoimmunology utilizes techniques from traditionally laboratory-based disciplines
      -for example, immunology, genomics, proteomics, neuroendocrinology, and cell
      biology--to reveal how the immune systems of wild organisms both shape and
      respond to ecological and evolutionary pressures. Immunological phenotypes are
      embedded within a mechanistic pathway leading from genotype through physiology to
      shape higher-order biological phenomena. As such, "mechanisms" in ecoimmunology
      can refer to both the within-host processes that shape immunological phenotypes,
      or it can refer the ways in which different immunological phenotypes alter
      between-organism processes at ecological and evolutionary scales. The mechanistic
      questions ecoimmunologists can ask, both within-organisms and between-organisms,
      however, often have been limited by techniques that do not easily transfer to
      wild, non-model systems. Thus, a major focus in ecoimmunology has been developing
      and refining the available toolkit. Recently, this toolkit has been expanding at
      an unprecedented rate, bringing new challenges to choosing techniques and
      standardizing protocols across studies. By confronting these challenges, we will
      be able to enhance ecoimmunological inquiries into the physiological basis of
      life-history trade-offs; the development of low-cost biomarkers for
      susceptibility to disease; and the investigation of the ecophysiological
      underpinnings of disease ecology, behavior, and the coevolution of host-parasite
      systems. The technical advances in, and crossover technologies from, disciplines
      associated with ecoimmunology and how these advances can help us understand the
      mechanistic basis of immunological variability in wild species were the focus of
      the symposium, Methods and Mechanisms in Ecoimmunology.

PMID- 24944114
TI  - Bone-free: soft mechanics for adaptive locomotion.
AB  - Muscular hydrostats (such as mollusks), and fluid-filled animals (such as
      annelids), can exploit their constant-volume tissues to transfer forces and
      displacements in predictable ways, much as articulated animals use hinges and
      levers. Although larval insects contain pressurized fluids, they also have
      internal air tubes that are compressible and, as a result, they have more
      uncontrolled degrees of freedom. Therefore, the mechanisms by which larval
      insects control their movements are expected to reveal useful strategies for
      designing soft biomimetic robots. Using caterpillars as a tractable model system,
      it is now possible to identify the biomechanical and neural strategies for
      controlling movements in such highly deformable animals. For example, the tobacco
      hornworm, Manduca sexta, can stiffen its body by increasing muscular tension (and
      therefore body pressure) but the internal cavity (hemocoel) is not iso
      barometric, nor is pressure used to directly control the movements of its limbs.
      Instead, fluid and tissues flow within the hemocoel and the body is soft and
      flexible to conform to the substrate. Even the gut contributes to the
      biomechanics of locomotion; it is decoupled from the movements of the body wall
      and slides forward within the body cavity at the start of each step. During
      crawling the body is kept in tension for part of the stride and compressive
      forces are exerted on the substrate along the axis of the caterpillar, thereby
      using the environment as a skeleton. The timing of muscular activity suggests
      that crawling is coordinated by proleg-retractor motoneurons and that the large
      segmental muscles produce anterograde waves of lifting that do not require
      precise timing. This strategy produces a robust form of locomotion in which the
      kinematics changes little with orientation. In different species of caterpillar,
      the presence of prolegs on particular body segments is related to alternative
      kinematics such as "inching." This suggests a mechanism for the evolution of
      different gaits through changes in the usage of prolegs, rather than, through
      extensive alterations in the motor program controlling the body wall. Some of
      these findings are being used to design and test novel control-strategies for
      highly deformable robots. These "softworm" devices are providing new insights
      into the challenges faced by any soft animal navigating in a terrestrial
      environment. 

PMID- 24944115
TI  - Stress, condition, and ornamentation.

PMID- 24944116
TI  - Cryptic genetic variation in natural populations: a predictive framework.
AB  - Understanding how populations respond to rapid environmental change is critical
      both for preserving biodiversity and for human health. An increasing number of
      studies have shown that genetic variation that has no discernable effect under
      common ecological conditions can become amplified under stressful or novel
      conditions, suggesting that environmental change per se can provide the raw
      materials for adaptation. Indeed, the release of such hidden, or "cryptic,"
      genetic variants has been increasingly viewed as playing a general and important
      role in allowing populations to respond to rapid environmental change. However,
      additional studies have suggested that there is a balance between cryptic genetic
      variants that are potentially adaptive in future environments and genetic
      variants that are deleterious. In this article, we begin by discussing how
      population and environmental parameters-such as effective population size and the
      historical frequency and strength of selection under inducing conditions
      influence relative amounts of cryptic genetic variation among populations and the
      overall phenotypic effects of such variation. The amount and distribution of
      cryptic genetic variation will, in turn, determine the likelihood that cryptic
      variants, once expressed, will be adaptive or maladaptive during environmental
      transitions. We then present specific approaches for measuring these parameters
      in natural populations. Finally, we discuss one natural system that will be
      conducive to testing whether populations that vary in these parameters harbor
      different amounts, or types, of cryptic genetic variation. Generally, teasing
      apart how population and environmental parameters influence the accumulation of
      cryptic genetic variation will help us to understand how populations endure and
      adapt (or fail to adapt) to natural environmental change and anthropogenic
      disturbance. 

PMID- 24944117
TI  - On the origins of parasite-extended phenotypes.
AB  - Parasites that adaptively manipulate the behavior of their host are among the
      most exciting adaptations that we can find in nature. The behavior of the host
      can become an extended phenotype of the parasites within animals such that the
      success and failure of the parasite's genome rely on precise change of the host's
      behavior. Evolutionary biology was borne from the close attention of naturalists
      such as Wallace and Darwin to phenotypic variation in seeking to understand the
      origins of new species. In this essay, I argue that we also need to think about
      the origins of parasite-extended phenotypes. This is a more difficult task than
      understanding the evolution of textbook examples of novelty such as the eyes of
      vertebrates or the hooves of horses. However, new tools such as phylogenomics
      provide an important opportunity to make significant progress in understanding
      the extended phenotypes of parasites. Knowing the origins of parasite-extended
      phenotypes is important as a goal all by itself. But the knowledge gained will
      also help us understand why complex manipulation is so rare and to identify the
      evolutionary tipping points driving its appearance. 

PMID- 24944118
TI  - The evolution of honest communication: integrating social and physiological costs
      of ornamentation.
AB  - Much research on animal communication has addressed how costs such as social
      costs or physiological costs favor the accuracy of signals. Previous work has
      largely considered these costs separately, but we may be missing essential
      connections by studying costs in isolation. After all, social interactions
      produce rapid changes in hormone titers which can then affect individual behavior
      and physiology. As a result, social costs are likely to have widespread
      physiological consequences. Here, I present a new perspective on the factors that
      maintain honest signals by describing how the interplay between social costs and
      physiological costs may maintain an accurate link between an animal's abilities
      and ornament elaboration. I outline three specific mechanisms by which the
      interaction between social behavior and hormones could favor honest signals and
      present specific predictions for each of the three models. Then, I review how
      ornaments alter agonistic behavior, agonistic behavior influences hormones, and
      how these hormonal effects influence fitness. I also describe the few previous
      studies that have directly tested how ornaments influence hormones. Finally,
      opportunities for future work are discussed. Considering the interaction between
      social behavior and physiology may address some challenges associated with both
      social and physiological models of costs. Understanding the dynamic feedbacks
      between physiology and social costs has potential to transform our understanding
      of the stability of animals' communication systems. 

PMID- 24944119
TI  - Reduction of water surface tension significantly impacts gecko adhesion
      underwater.
AB  - The gecko adhesive system is dependent on weak van der Waals interactions that
      are multiplied across thousands of fine hair-like structures (setae) on geckos'
      toe pads. Due to the requirements of van der Waals forces, we expect that any
      interruption between the setae and substrate, such as a water layer, will
      compromise adhesion. Our recent results suggest, however, that the air layer
      (plastron) surrounding the superhydrophobic toe pads aid in expelling water at
      the contact interface and create strong shear adhesion in water when in contact
      with hydrophobic surfaces. To test the function of the air plastron, we reduced
      the surface tension of water using two surfactants, a charged anionic surfactant
      and a neutral nonionic surfactant. We tested geckos on three substrates:
      hydrophilic glass and two hydrophobic surfaces, glass with a octadecyl
      trichlorosilane self-assembled monolayer (OTS-SAM) and polytetrafluoroethylene
      (PTFE). We found that the anionic surfactant inhibited the formation of the air
      plastron layer and significantly reduced shear adhesion to all three substrates.
      Interestingly, the air plastron was more stable in the nonionic surfactant
      treatments than the anionic surfactant treatments and we found that geckos
      adhered better in the nonionic surfactant than in the anionic surfactant on OTS
      SAM and PTFE but not on glass. Our results have implications for the evolution of
      a superhydrophobic toe pad and highlight some of the challenges faced in
      designing synthetic adhesives that mimic geckos' toes. 

PMID- 24944123
TI  - Benefits of metastasectomy for colorectal cancer.

PMID- 24944120
TI  - Antimicrobial drugs for treating cholera.
AB  - BACKGROUND: Cholera is an acute watery diarrhoea caused by infection with the
      bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death.
      Effective management requires early diagnosis and rehydration using oral
      rehydration salts or intravenous fluids. In this review, we evaluate the
      additional benefits of treating cholera with antimicrobial drugs. OBJECTIVES: To
      quantify the benefit of antimicrobial treatment for patients with cholera, and
      determine whether there are differences between classes of antimicrobials or
      dosing schedules. SEARCH METHODS: We searched the Cochrane Infectious Disease
      Group Specialized Register; the Cochrane Central Register of Controlled Trials
      (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index;
      metaRegister of Controlled Trials; WHO International Clinical Trials Registry
      Platform; conference proceedings; and reference lists to March 2014. SELECTION
      CRITERIA: Randomized and quasi-randomized controlled clinical trials in adults
      and children with cholera that compared: 1) any antimicrobial treatment with
      placebo or no treatment; 2) different antimicrobials head-to-head; or 3)
      different dosing schedules or different durations of treatment with the same
      antimicrobial. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied
      inclusion and exclusion criteria, and extracted data from included trials.
      Diarrhoea duration and stool volume were defined as primary outcomes. We
      calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes,
      with 95% confidence intervals (CI), and pooled data using a random-effects meta
      analysis. The quality of evidence was assessed using the GRADE approach. MAIN
      RESULTS: Thirty-nine trials were included in this review with 4623 participants.
      Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy
      shortened the mean duration of diarrhoea by about a day and a half compared to
      placebo or no treatment (MD -36.77 hours, 95% CI -43.51 to -30.03, 19 trials,
      1013 participants, moderate quality evidence). Antimicrobial therapy also reduced
      the total stool volume by 50% (ROM 0.5, 95% CI 0.45 to 0.56, 18 trials, 1042
      participants, moderate quality evidence) and reduced the amount of rehydration
      fluids required by 40% (ROM 0.60, 95% CI 0.53 to 0.68, 11 trials, 1201
      participants, moderate quality evidence). The mean duration of fecal excretion of
      vibrios was reduced by almost three days (MD 2.74 days, 95% CI -3.07 to -2.40, 12
      trials, 740 participants, moderate quality evidence).There was substantial
      heterogeneity in the size of these benefits, probably due to differences in the
      antibiotic used, the trial methods (particularly effective randomization), and
      the timing of outcome assessment. The benefits of antibiotics were seen both in
      trials recruiting only patients with severe dehydration and in those recruiting
      patients with mixed levels of dehydration. Comparisons of antimicrobials In head
      to-head comparisons, there were no differences detected in diarrhoea duration or
      stool volume for tetracycline compared to doxycycline (three trials, 230
      participants, very low quality evidence); or tetracycline compared to
      ciprofloxacin or norfloxacin (three trials, 259 participants, moderate quality
      evidence). In indirect comparisons with substantially more trials, tetracycline
      appeared to have larger benefits than doxycycline, norfloxacin and trimethoprim
      sulfamethoxazole for the primary review outcomes.Single dose azithromycin
      shortened the duration of diarrhoea by over a day compared to ciprofloxacin (MD 
      32.43, 95% CI -62.90 to -1.95, two trials, 375 participants, moderate quality
      evidence) and by half a day compared to erythromycin (MD -12.05, 95% CI -22.02 to
      -2.08, two trials, 179 participants, moderate quality evidence). It was not
      compared with tetracycline. AUTHORS' CONCLUSIONS: In treating cholera,
      antimicrobials result in substantial improvements in clinical and microbiological
      outcomes, with similar effects observed in severely and non-severely ill
      patients. Azithromycin and tetracycline may have some advantages over other
      antibiotics.

PMID- 24944122
TI  - Optimal method for short-term or long-term islet preservation: comparison of
      islet culture, cold preservation and cryopreservation.
AB  - Islet preservation plays an important role for the success of islet
      transplantation. To determine the optimal method for islet preservation, we
      compared the outcomes of islet culture, cold preservation, and cryopreservation
      in this study. Isolated rat islets were divided into three groups: 37  degrees C
      group (conventional culture at 37  degrees C in RPMI-1640 medium), 4  degrees C
      group (cold preservation at 4  degrees C in University of Wisconsin (UW)
      solution), and -80  degrees C group (cryopreservation at -80  degrees C with
      dimethyl sulfoxide (DMSO)). Recovery rate, Calcein-AM/PI double staining, insulin
      release, mRNA level of hypoxia-inducible factor-1alpha (HIF-1alpha), and protein
      level of Bax in islets were examined after short-term (1 day) or long-term (7
      days) preservation. After either short-term or long-term preservation, 4  degrees
      C group showed higher recovery rate of the islets number, lower percentage of PI
      positive area, better insulin release ability, and lower expression levels of HIF
      1alpha and Bax in comparison to the 37 or -80  degrees C group. Meanwhile, islets
      in 37  degrees C group showed better function, and down-regulation of HIF-1alpha
      and Bax than those in -80  degrees C group on day 1; however, worse function of
      islets, up-regulated HIF-1alpha and Bax in 37  degrees C group were observed in
      comparison to -80  degrees C group on day 7. These results suggest that cold
      preservation at 4  degrees C in UW solution is the optimal method in comparison
      to the conventional culture at 37  degrees C or cryopreservation at -80  degrees
      C for short-term or long-term islet preservation. Furthermore, the potential
      mechanism may relate to, at least in part, apoptosis induced by the HIF-1alpha. 

PMID- 24944121
TI  - Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using an
      IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex.
AB  - Bispecific antibodies (BsAb) have proven to be useful targeting vectors for
      pretargeted radioimmunotherapy (PRIT). We sought to overcome key PRIT limitations
      such as high renal radiation exposure and immunogenicity (e.g., of streptavidin
      antibody fusions), to advance clinical translation of this PRIT strategy for
      diasialoganglioside GD2-positive [GD2(+)] tumors. For this purpose, an IgG-scFv
      BsAb was engineered using the sequences for the anti-GD2 humanized monoclonal
      antibody hu3F8 and C825, a murine scFv antibody with high affinity for the
      chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)
      complexed with beta-particle-emitting radiometals such as (177)Lu and (90)Y. A
      three-step regimen, including hu3F8-C825, a dextran-based clearing agent, and p
      aminobenzyl-DOTA radiolabeled with (177)Lu (as (177)Lu-DOTA-Bn; t1/2 = 6.71
      days), was optimized in immunocompromised mice carrying subcutaneous human GD2(+)
      neuroblastoma (NB) xenografts. Absorbed doses for tumor and normal tissues were
      approximately 85 cGy/MBq and <=3.7 cGy/MBq, respectively, with therapeutic
      indices (TI) of 142 for blood and 23 for kidney. A therapy study (n = 5/group;
      tumor volume, 240 +/- 160 mm(3)) with three successive PRIT cycles (total
      (177)Lu: ~33 MBq; tumor dose ~3,400 cGy), revealed complete tumor response in 5
      of 5 animals, with no recurrence up to 28 days after treatment. Tumor ablation
      was confirmed histologically in 4 of 5 mice, and normal organs showed minimal
      overall toxicities. All nontreated mice required sacrifice within 12 days (>1.0
      cm(3) tumor volume). We conclude that this novel anti-GD2 PRIT approach has
      sufficient TI to successfully ablate subcutaneous GD2(+)-NB in mice while sparing
      kidney and bone marrow.

PMID- 24944124
TI  - Clostridium perfringens and Clostridium difficile in cooked beef sold in Cote
      d'Ivoire and their antimicrobial susceptibility.
AB  - The aim of this study was to evaluate the prevalence of Clostridium difficile and
      Clostridium perfringens in cooked beef sold in the streets in Cote d'Ivoire and
      their antimicrobial susceptibility. A total of 395 kidney and flesh samples of
      cooked beef were collected from vendors at Abidjan and subjected to C. difficile
      and C. perfringens isolation and identification by using biochemical tests, API
      20A system and PCR detection. Subsequently, the antimicrobial susceptibility test
      was performed for confirmed isolates. Our results showed the prevalence of 12.4%
      for C. difficile (11.04% in kidney and 13.45% in flesh) and 5.06% for C.
      perfringens (2.32% in kidney and 7.17% in flesh). Metronidazole and vancomycin
      remained the most potent antimicrobial agents against C. difficile while
      metronidazole and penicillin G were the most potent agents against C.
      perfringens. The resistance rates to tetracycline, doxycycline, chloramphenicol
      and erythromycin against C. difficile and C. perfringens isolates ranged from
      2.05% to 8.16% and from 20% to 50%, respectively. Among all antimicrobial agents
      tested against C. difficile, percentages of resistance to quinolones
      ciprofloxacin, norfloxacin and nalidixic acid as well as to gentamicin and
      cefotaxime were the highest. Eight resistant phenotypes were defined for C.
      difficile isolates and eleven resistant phenotypes for C. perfringens isolates.
      Clindamycin/gentamicin/cefotaxime/ciprofloxacin/norfloxacin/nalidixic acid
      resistance was the most common phenotype for C. difficile (55.10% of isolates)
      while norfloxacin/nalidixic acid resistance was the most common phenotype for C.
      perfringens (20% of isolates). 

PMID- 24944125
TI  - The transfer of social exclusion and inclusion functions through derived stimulus
      relations.
AB  - Previous studies have found that social exclusion can cause distress to those
      excluded. One method used to study social exclusion is through a virtual ball
      toss game known as Cyberball. In this game, participants may be excluded from or
      included in the ball-toss game and typically report lower feelings of self
      esteem, control, belonging, and meaningful existence following exclusion.
      Experiments 1 and 2 sought to explore the transfer of feelings of exclusion and
      inclusion through stimulus equivalence classes. In both experiments, participants
      were trained to form two three-member equivalence classes (e.g., A1-B1, B1-C1; A2
      B2, B2-C2) and were tested with novel stimulus combinations (A1-C1, C1-A1, A2-C2,
      C2-A2). Thereafter, participants were exposed to the Cyberball exclusion and
      inclusion games. In these games, one stimulus (C1) from one equivalence class was
      assigned as the Cyberball inclusion game name, whereas one stimulus (C2) from the
      other equivalence class was assigned as the Cyberball exclusion game name. In
      Experiment 2, participants were only exposed to the Cyberball exclusion game.
      During a subsequent transfer test, participants were asked to rate how included
      in or excluded from they thought they would be in other online games,
      corresponding to members of both equivalence classes. Participant reported that
      they felt they would be excluded from online games if the games were members of
      the same equivalence class as C2. In contrast, participants reported that they
      felt they would be included in online games if the games were members of the same
      equivalence class as C1. Results indicated the transfer of feelings of inclusion
      (Experiment 1) and feelings of exclusion (Experiments 1 and 2) through
      equivalence classes.

PMID- 24944127
TI  - Football for health - science proves that playing football on a regular basis
      contributes to the improvement of public health.

PMID- 24944129
TI  - Effects of a 5-month football program on perceived psychological status and body
      composition of overweight boys.
AB  - The effects of a 5-month intervention of football instruction and practice on the
      perceived psychological status and body composition of overweight boys were
      examined. Twelve boys (8-12 years; body mass index >= 85th percentile)
      participated in a structured 5-month football program, consisting of four weekly
      60-90 min sessions with mean heart rate > 80%HRmax [football group (FG)]. A
      control group (CG) included eight boys of equivalent age from an obesity clinic
      located in the same area as the school. Both groups participated in two sessions
      of 45-90-min physical education per week at school. Indicators of perceived
      psychological status included body image, self-esteem, attraction to
      participation in physical activity, and perceived physical competence measured
      with standardized questionnaires. Body composition was evaluated using dual
      energy X-ray absorptiometry. From baseline through 5 months, FG improved (P <
      0.05) in all indicators of psychological status (%Delta = +11.7 to +29.2%)
      compared with CG (%Delta = -32.1 to +0.5%). Changes in percentage body fat and
      lean body mass, however, did not differ between FG and CG. The findings suggest
      that a 5-month football intervention program was effective in improving the
      psychological status of overweight boys but did not significantly alter body
      composition.

PMID- 24944128
TI  - Structural and functional cardiac adaptations to a 10-week school-based football
      intervention for 9-10-year-old children.
AB  - The present study investigated the cardiac effects of a 10-week football training
      intervention for school children aged 9-10 years using comprehensive
      transthoracic echocardiography as a part of a larger ongoing study. A total of 97
      pupils from four school classes were cluster-randomized into a control group that
      maintained their usual activities (CON; two classes, n = 51, 21 boys and 30
      girls) and a football training group that performed an additional 3 * 40 min of
      small-sided football training per week (FT; two classes, n = 46, 23 boys and 23
      girls). No baseline differences were observed in age, body composition, or
      echocardiographic variables between FT and CON. After the 10-week intervention,
      left ventricular posterior wall diameter was increased in FT compared with CON
      [0.4 +/- 0.7 vs -0.1 +/- 0.6 (+/- SD) mm; P < 0.01] as was the interventricular
      septum thickness (0.2 +/- 0.7 vs -0.2 +/- 0.8 mm; P < 0.001). Global
      isovolumetric relaxation time increased more in FT than in CON (3.8 +/- 10.4 vs 
      0.9 +/- 6.6 ms, P < 0.05) while the change in ventricular systolic ejection
      fraction tended to be higher (1.4 +/- 8.0 vs -1.1 +/- 5.5%; P = 0.08). No changes
      were observed in resting heart rate or blood pressure. In conclusion, a short
      term, school-based intervention comprising small-sided football sessions resulted
      in significant structural and functional cardiac adaptations in pre-adolescent
      children.

PMID- 24944130
TI  - Effect of game format on heart rate, activity profile, and player involvement in
      elite and recreational youth players.
AB  - The purpose of this study was to evaluate activity profile, aerobic load, and
      player involvement in two game formats of recreational and elite youth football
      for two age groups. A total of 152 youth players participated, with 45 U10
      players playing 5v5 and 8v8 games, and 41 U13 players playing 8v8 and 11v11 (20
      min) games. Activity profile, heart rate (HR), and technical actions were
      measured during all games using 10 Hz GPS, video filming, and HR monitors. For
      U10, no difference was found in total distance covered (1754 +/- 237 vs 1771 +/-
      314 m, P = 0.650, d = 0.06), whereas mean HR (174 +/- 10 vs 168 +/- 12 bpm, P =
      0.001, d = 0.59) and number of technical actions (65.1 +/- 24.0 vs 36.9 +/- 20.4,
      P    0.001, d = 1.27) were higher in 5v5 than in 8v8. For U13, lower total
      distance covered (1821 +/- 325 vs 2038 +/- 328 m, P < 0.001, d = 0.66) and higher
      number of technical actions (36.2 +/- 14.9 vs 26.9 +/- 14.1, P < 0.001, d = 0.64)
      were observed in 8v8 than in 11v11, with no difference in mean HR (170 +/- 10 vs
      171 +/- 10 bpm, P = 0.679, d = 0.10). In conclusion, HR is high in youth football
      matches irrespective of the level of play and the game format. Playing with fewer
      players on smaller pitches results in minor changes to the physical loading but
      elevates the technical involvement of youth players both at elite level and
      recreational level.

PMID- 24944131
TI  - Football training improves cardiovascular health profile in sedentary,
      premenopausal hypertensive women.
AB  - The present study examined the effects of short-term recreational football
      training on blood pressure (BP), fat mass, and fitness in sedentary, 35-50-year
      old premenopausal women with mild hypertension. Forty-one untrained, hypertensive
      women were randomized into a football training group (n = 21; FTG) and a control
      group (n = 20; CON). FTG performed 45 +/- 1 1-h small-sided football training
      sessions during the 15-week intervention period. BP, body composition (dual
      energy x-ray absorptiometry), blood lipid profile, and fitness level were
      determined pre- and post-intervention. After 15 weeks, systolic and diastolic BP,
      respectively, were lowered more (P < 0.05) in FTG (-12 +/- 3 and -6 +/- 2 mmHg)
      than in CON (-1 +/- 1 and 1 +/- 2 mmHg). Total body fat mass decreased more (P <
      0.05) in FTG than in CON during the 15-week intervention period (-2.3 +/- 0.5 kg
      vs 0.4 +/- 0.3 kg). After 15 weeks, both total cholesterol (-0.4 +/- 0.1 mmol/L
      vs 0.1 +/- 0.2 mmol/L) and triglyceride (-0.2 +/- 0.1 mmol/L vs 0.3 +/- 0.2
      mmol/L) were lowered more (P < 0.05) in FTG than in CON. Yo-Yo intermittent
      endurance level 1 test performance increased more (P < 0.05) in FTG than in CON
      (111 +/- 18% vs 1 +/- 3%) during the 15-week intervention period. In conclusion,
      short-term football training resulted in a marked reduction in BP and induced
      multiple improvements in fitness and cardiovascular health profile of untrained,
      premenopausal women with mild hypertension.

PMID- 24944132
TI  - Positive effects of football on fitness, lipid profile, and insulin resistance in
      Brazilian patients with type 2 diabetes.
AB  - We evaluated the effects of recreational football training combined with calorie
      restricted diet (football + diet) vs calorie-restricted diet alone (diet) on
      aerobic fitness, lipid profile, and insulin resistance indicators in type 2
      diabetes (T2D) patients. Forty-four T2D patients aged 48-68 years (27 females, 17
      males) were randomly allocated to the football + diet group (FDG; n = 22) or to
      the diet group (DG; n = 22), of whom 19 FDG and 15 DG subjects completed the
      study. The football training was performed for 3 * 40 min/week for 12 weeks. Dual
      energy X-ray absorptiometry scanning, treadmill testing, and fasting blood
      samplings were performed pre and post-intervention. After 12 weeks, maximal
      oxygen uptake (VO2max ) was elevated (P < 0.05) by 10 +/- 4% in FDG but not in DG
      (-3 +/- 4%, P < 0.05). After 12 weeks, reductions in blood triglycerides (0.4 +/-
      0.1 mmol/L), total cholesterol (0.6 +/- 0.2 mmol/L), low-density lipoprotein, and
      very low-density lipoprotein levels were observed only in FDG. Fat mass decreased
      (P < 0.05) by 3.4 +/- 0.4 kg in FDG and 3.7 +/- 0.4 kg in DG. The lower (P <
      0.05) glucagon and homeostatic model assessment of insulin resistance indicated
      an improvement in insulin sensitivity in FDG. In conclusion, football combined
      with restricted diet was effective in enhancing VO2max , reducing total
      cholesterol and triglycerides, and increasing insulin sensitivity, potentially
      providing better tools for the prevention of T2D complications than diet alone.

PMID- 24944133
TI  - Health promotion: the impact of beliefs of health benefits, social relations and
      enjoyment on exercise continuation.
AB  - The aim of this study was to explore how and why participants in structured
      exercise intervention programs continue or stop exercising after the program is
      finished. We conducted four focus group interviews with four groups of middle
      aged and elderly men (total n = 28) who had participated in exercise
      interventions involving playing either a team sport (football) or a more
      individually focused activity (spinning and crossfit). Our results show that
      different social, organizational and material structures inherent in the
      different activities shape the subjects' enjoyment of exercise participation, as
      well as their intention and ability to continue being active. In conclusion, team
      sport activities seem to be intrinsically motivating to the participants through
      positive social interaction and play. They are therefore more likely to result in
      exercise continuation than activities that rely primarily on extrinsic motivation
      such as the expectation of improved health and well-being.

PMID- 24944134
TI  - Football training improves lean body mass in men with prostate cancer undergoing
      androgen deprivation therapy.
AB  - Androgen deprivation therapy (ADT) remains a cornerstone in the management of
      patients with prostate cancer (PCa) despite adverse effects on body composition
      and functional parameters. We compared the effects of football training with
      standard care in PCa patients managed with ADT (> 6 months). Fifty-seven men aged
      67 (range: 43-74) were randomly assigned to a football group (FG, n = 29) or a
      usual care control group (CON, n = 28). The primary outcome was change in lean
      body mass (LBM) assessed by dual-energy X-ray absorptiometry scanning. Secondary
      outcomes included changes in knee-extensor muscle strength (one repetition
      maximum), fat percentage, and maximal oxygen uptake (VO2max ). Mean heart rate
      during training was 137.7 (standard deviation 13.7) bpm or 84.6 (3.9)% HRmax. In
      FG, LBM increased by 0.5 kg [95% confidence interval (CI) 0.1-0.9; P = 0.02] with
      no change in CON (mean group difference 0.7 kg; 95% CI 0.1-1.2; P = 0.02). Also,
      muscle strength increased in FG (8.9 kg; 95% CI 6.0-11.8; P < 0.001) with no
      change in CON (mean group difference 6.7 kg; 95% CI 2.8-10.7; P < 0.001). In FG,
      VO2max increased (1.0 mL/kg/min; 95% CI 0.2-1.9; P = 0.02) and fat percentage
      tended to decrease (0.7%; 95%CI 1.3-0.0; P = 0.06), but these changes were not
      significantly different from CON. In conclusion, football training over 12 weeks
      improved LBM and muscle strength compared with usual care in men with prostate
      cancer receiving ADT.

PMID- 24944135
TI  - "All boys and men can play football": a qualitative investigation of recreational
      football in prostate cancer patients.
AB  - Evidence is accumulating that exercise-based rehabilitation improves physical
      capacity and quality of life in cancer survivors. However, recruitment and
      persistence of male cancer patients in rehabilitation and physical activity are
      low and novel health promotion strategies are warranted. The purpose of this
      study was to gain an understanding of the meaning of recreational football as a
      team and interaction-oriented health-promoting activity in men with prostate
      cancer (n = 26). Qualitative data were collected through six focus group
      interviews (n = 4-6) and 20 h of participant observations. The two data sets were
      analyzed using framework analysis. The analysis produced 11 subthemes that were
      structured into three overarching themes: (a) motivational drivers; (b) united in
      sport; and (c) confirmation of own capacity. The findings indicated that
      participants regarded football as a welcome opportunity to regain control and
      acquire a sense of responsibility for own health without assuming the patient
      role, and football training legitimized and promoted mutual caring behavior in a
      male-oriented context. In conclusion, the study suggests that football, due to
      its cultural representation of masculine ideals, may be a potent and unique
      strategy for increasing recruitment and adherence to physical activity in
      prostate cancer patients.

PMID- 24944136
TI  - Street football is a feasible health-enhancing activity for homeless men:
      biochemical bone marker profile and balance improved.
AB  - This case-control study investigated the feasibility of street football as a
      health-enhancing activity for homeless men, specifically the musculoskeletal
      effects of 12 weeks of training. Twenty-two homeless men participated in the
      football group (FG) and 10 served as controls (C). Plasma osteocalcin, TRACP5b,
      leptin, and postural balance were measured, and whole-body DXA scanning was
      performed. The attendance rate was 75% (2.2 +/- 0.7 sessions per week). During 60
      min of training, the total distance covered was 5534 +/- 610 m, with 1040 +/-
      353, 2744 +/- 671, and 864 +/- 224 m covered by high-intensity, low-intensity,
      and backwards/sideways running, respectively. In FG, osteocalcin increased by 27%
      from 20.1 +/- 11.1 to 25.6 +/- 11.8 ng/mL (P = 0.007). Postural balance increased
      by 39% (P = 0.004) and 46% (P = 0.006) in right and left leg. Trunk bone mineral
      density increased by 1.0% from 0.959 +/- 0.095 to 0.969 +/- 0.090 g/cm(2) (P =
      0.02). No effects were observed in C. In conclusion, street football appears to
      be a feasible training activity with musculoskeletal health benefits for homeless
      men. The attendance rate and the training intensity were high, and 12 weeks of
      training resulted in a substantial anabolic response in bone metabolism. Postural
      balance improved markedly, and the overall risk of falling, and hospitalization
      due to sudden trauma, could be reduced by street football for homeless men.

PMID- 24944137
TI  - Physiological response and activity profile in recreational small-sided football:
      no effect of the number of players.
AB  - We examined the effect of the number of players on the activity profile and
      physiological response to small-sided recreational football games with fixed
      relative pitch size. Twelve untrained men (age: 33.0 +/- 6.4 (+/- standard
      deviation) years, fat%: 22.4 +/- 6.1%, VO2 max: 43.3 +/- 5.2 mL/min/kg) completed
      three football sessions of 4 times 12 min with 3v3, 5v5, or 7v7 in a randomized
      order. Pitch sizes were 80 m(2) per player. Activity profile (10 Hz global
      positioning system), heart rate (HR), and rating of perceived exertion (RPE) were
      measured, and blood samples were collected before and during games. Average HR
      was 84.1 +/- 3.9, 84.5 +/- 5.0, and 82.8 +/- 5.1 %HRmax for 3v3, 5v5, and 7v7,
      respectively, with no difference between game formats. High blood lactate (5.9 +/
      2.9, 5.9 +/- 2.4, and 5.5 +/- 2.9 mmol/L) and plasma NH3 concentrations (124 +/-
      48, 112 +/- 38, and 126 +/- 55 MUmol/L, respectively) were observed during 3v3,
      5v5, and 7v7, respectively, with no difference between formats. Similar total
      distance (3676 +/- 478, 3524 +/- 467, and 3577 +/- 500 m), high-intensity
      distance (349 +/- 145, 406 +/- 134, and 409 +/- 165 m), and RPE (4.7 +/- 1.6, 4.9
      +/- 2.1, and 4.6 +/- 1.8) were also observed. The number of intense accelerations
      (500 +/- 139 vs 459 +/- 143 and 396 +/- 144) were higher (P < 0.05) during 3v3
      than 5v5 and 7v7. In conclusion, the intensity is high during small-sided
      recreational football games, with similar physiological responses for 6-14
      players when pitch size is adapted, providing further evidence that effective
      recreational football training is easy to organize.

PMID- 24944138
TI  - Football Fitness - a new version of football? A concept for adult players in
      Danish football clubs.
AB  - This article explores a new Danish football-based activity for health called
      Football Fitness (FF). Data are from quantitative and qualitative methods, and
      the theoretical framework for the analysis of the organizational form of FF is
      the theory of path dependency (Mahoney) and first- and second-order change
      (Watzlawick et al.). Theories of Pestoff concerning differences between state,
      market, and the civil society and theories of voluntary associations in a Danish
      context (Kaspersen & Ottesen; Ibsen & Seippel) are applied. This article
      indicates how FF is a result of the changing landscape of sport and argues that
      it can be beneficial to target sports organizations and include the expertise of
      non-profit sports clubs if the goal is to raise the physical activity level of
      the local community and make these long lasting. But the organizations need to
      consider how this is to be done. FF, established by the Danish Football
      Association (FA) and managed by the voluntary clubs, is one example in a Danish
      context. Data indicate that FF is beneficial to the clubs involved in a number of
      ways. Among other things, it attracts new user groups and improves the club
      environment, including social activities and parental environment. 

PMID- 24944139
TI  - Executive summary: Football for health - prevention and treatment of non
      communicable diseases across the lifespan through football.
AB  - This supplement contains 16 original articles describing how football conducted
      as small sided games affects fitness and health of untrained individuals across
      the lifespan. The intermittent nature of football and high exercise intensity
      result in a broad range of effects. The heart changes its structure and improves
      its function. Blood pressure is markedly reduced with the mean arterial blood
      pressure being lowered by ~10 mmHg for hypertensive men and women training 2-3
      times/week for 12-26 weeks. Triglycerides and cholesterol are lowered and body
      fat declines, especially in middle-aged men and women with type 2 diabetes.
      Furthermore, muscle mass and bone mineral density increases in a number of
      participant groups, including 65-75-year-old men. The functional capacity is
      elevated with increases in VO2 max of 10-15%, and 50-100% improvements in the
      capacity to perform intermittent work within 16 weeks. These effects apply
      irrespective of whether the participants are young, overweight, elderly or
      suffering from a disease. The studies clearly show that the participants enjoy
      playing football and form special relationships with their team mates. Thus,
      football is a healthy activity, providing a unique opportunity to increase
      recruitment and adherence to physical activity in a hitherto underserved
      population, and to treat and rehabilitate patients with hypertension, type 2
      diabetes and prostate cancer.

PMID- 24944140
TI  - Relationship between left ventricular twist and circulating biomarkers of
      collagen turnover in hypertensive patients with heart failure.
AB  - BACKGROUND: Left ventricular (LV) twist may be a compensatory mechanism to
      preserve ejection fraction (EF). In patients with hypertension, twist varies
      depending on the left ventricle's degree of remodeling and systolic function; it
      is increased in those with hypertension with normal EF (HTNEF) and diminished in
      those with hypertension with low EF (HTLEF). The ratio of collagen-degradation
      biomarkers in patients with hypertension is higher in those with low EFs than
      those with preserved EFs and may contribute to remodeling and systolic
      dysfunction. METHODS: The aim of this study was to evaluate the relationship
      between these biomarkers and LV twist in 82 patients with hypertension, 41 with
      EFs < 50% (HTLEF group) and 41 with EFs >= 50% (HTNEF group). Net LV twist was
      measured using speckle-tracking echocardiography. Markers of collagen turnover,
      including serum concentrations of matrix metalloproteinase-1 (MMP1), tissue
      inhibitor of MMP1 (TIMP1), and the ratio of MMP1 to TIMP1, were measured.
      RESULTS: Log TIMP1, log MMP1, and log MMP1/TIMP1 ratio levels were higher in the
      HTLEF group than the HTNEF group (12.3 +/- 0.3 vs 11.8 +/- 0.1 [P < .0001], 9.1
      +/- 0.3 vs 8.0 +/- 0.2 [P < .0001], and -3.3 +/- 0.3 vs -3.8 +/- 0.2 [P < .0001],
      respectively). Net LV twist was lower in the HTLEF group than the HTNEF group
      (3.3 +/- 1.1 vs 11.7 +/- 0.7, P < .0001). An inverse correlation existed between
      log MMP1/TIMP1 and net LV twist after adjusting for age, EF, duration of heart
      failure, systolic blood pressure, LV mass index, and LV sphericity index at end
      diastole (r = -0.43, P < .0001). CONCLUSIONS: This inverse correlation between
      twist and loss of myocardial collagen scaffolding in patients with hypertension
      with heart failure suggests that the integrity of the extracellular matrix may
      play an important role in preserving myocardial deformation.

PMID- 24944141
TI  - Associations of common carotid intima-media thickness with coronary heart disease
      risk factors and events vary with distance from the carotid bulb.
AB  - BACKGROUND: Common carotid artery (CCA) intima-media thickness (IMT) can be
      measured using ultrasound near to or below the carotid bulb. This might affect
      associations of IMT with coronary heart disease (CHD) risk factors and events.
      METHODS: IMT measurements were performed near and below the divergence of the CCA
      bulb in 279 white individuals aged 45 to 54 years free of CHD at baseline and a
      subset of the Multi-Ethnic Study of Atherosclerosis, a cohort composed of whites,
      blacks, Chinese, and Hispanic subjects. Participants were followed for an average
      of 8.2 years. Far wall mean of the maximum IMT (MMaxIMT) and mean of the mean IMT
      of the right and left CCAs were averaged. Framingham risk factors were used in
      multivariate linear regression models. Parsimonious Cox proportional regression
      models included first-time CHD as outcome. RESULTS: Mean of the mean IMT below
      the bulb was smaller than near the bulb (0.51 +/- 0.078 vs 0.56 +/- 0.088 mm, P <
      .001) and had similar associations with risk factors (model R(2) = 0.215 vs
      0.186). MMaxIMT below the bulb was associated with risk factors (model R(2) =
      0.211), but MMaxIMT near to the bulb was not (R(2) = 0.025). Mean of the mean IMT
      and MMaxIMT below the bulb were associated with CHD events (hazard ratios, 1.67
      [P = .047] and 1.72 [P = .037], respectively) but not when measured near the
      bulb. CONCLUSIONS: CCA IMT measurements made below the bulb are smaller but have
      more consistent associations with CHD risk factors and outcomes compared with IMT
      measured near the bulb.

PMID- 24944142
TI  - Physical activity patterns among school children in India.
AB  - OBJECTIVE: To assess the prevalence of physical activity and its relation with
      socio-demographic variables and eating habits among school-aged children in
      India. METHODS: The study incorporated secondary analysis of anthropometric
      measurements and questionnaires on lifestyle and dietary habits of 1,680 school
      children aged between 3 and 11 y, obtained while carrying out the OBEY-AD
      project. The inventory contained questions about several variables concerning to
      physical activity, educational background, lifestyles and eating habits for both
      children and parents. Questions were organized along specific contents, which
      could be informative topics, picture choices and multiple answers choices.
      RESULTS: Prevalence of inactivity was 21% and exhibited significant variations
      between cities. Physical activity was significantly associated to socio-economic
      status and consumption of fruits and vegetables. No association could be revealed
      with children's BMI. CONCLUSIONS: Health-promotion interventions aimed at
      improving healthy lifestyles in Indian children should focus on population strata
      with low socio-economic status.

PMID- 24944143
TI  - Effect of supplementation with iron fortified biscuits on the hemoglobin status
      of children in rural areas of Shimoga, Karnataka.
AB  - OBJECTIVE: To assess the efficacy of iron fortified biscuits, in high and low
      dosages, on the hemoglobin levels of anemic school going children aged 6 to 12 y.
      METHODS: The nutrition intervention was conducted in primary schools located in
      villages at Shimoga district, Karnataka. School children aged 6 to 12 y who were
      anemic, with hemoglobin level <11.5 g/dl were considered for the nutrition
      intervention. The sampling design undertaken was quasi experimental with pre and
      post stages of outcome. The children enrolled were divided into two groups. One
      group received high dosage of iron fortified biscuits (30 mg of elemental iron/6
      biscuits) and the second group received a relatively lower dosage of iron
      fortified biscuits (1.8 mg of elemental iron/6 biscuits) for a period of 120 d.
      The hemoglobin levels were estimated pre and post fortified biscuit
      supplementation by cyanomethemoglobin method. RESULTS: There was an increase in
      the mean hemoglobin level of children which was found to be higher in group I
      (high iron fortified biscuits) (1.06 g/dl) compared to group II (low iron
      fortified biscuits) (0.41 g/dl), significant at 0.01 level (t = 3.84**).
      CONCLUSIONS: In the current nutrition intervention, both high and low iron
      fortified biscuits led to a significant enhancement in the body weight and
      hemoglobin status of anemic school children in a rural setup. The nutrition
      intervention clearly highlights biscuits as an ideal fortification vehicle for
      addressing anemia.

PMID- 24944145
TI  - Undescended thymus: a rare cause of midline neck swelling.

PMID- 24944144
TI  - Surveillance for infectious complications in pediatric acute liver failure - a
      prospective study.
AB  - OBJECTIVE: To prospectively evaluate infectious complications (IC) in pediatric
      acute liver failure (PALF) by employing surveillance cultures. METHODS: From 2011
      to 2013, children with PALF in a tertiary care centre received a standard
      protocolised management. Prophylactic parenteral antibiotics were used without
      antifungals. Surveillance cultures of blood, urine, ascites and tracheal
      aspirates were sent. Biochemical and clinical parameters and outcomes were
      compared between children with and without IC. RESULTS: Of the 29 children with
      PALF admitted during the study period (median age 36 mo, range 12-90 mo), 13.8 %
      had blood stream infections (BSI) at admission. Organisms were isolated in 8.8 %
      (12/136) of the blood cultures, 13.7 % (11/80) of the urine cultures, 30.8 %
      (8/26) of the tracheal aspirates and 7.1 % (1/14) of the ascitic fluid cultures.
      Gram negative bacteriae (n = 17) were the commonest, followed by fungi (n = 13)
      and gram positive bacteriae (n = 2). Klebsiella pneumoniae and Candida
      nonalbicans group were the commonest bacteria and fungi respectively. After
      admission, fungal BSI and urinary tract infections were diagnosed at a median
      time of 4 d (range 3-8 d) and 3.5 d (range 3-6 d) respectively. ICs were not
      associated with other complications and increased mortality but with longer
      hospital and pediatric intensive care unit (PICU) stay. CONCLUSIONS: In this
      study BSI was a common finding at admission in PALF. Inspite of prophylactic
      antibiotics, break through gram negative bacterial and fungal ICs were common.
      Empirical treatment of IC should include broad spectrum antibiotics. Fungal IC
      occurred beyond 48 h. Prophylactic antifungals at admission may be considered to
      decrease their frequency. IC prolongs PICU and hospital stay.

PMID- 24944146
TI  - Pierson syndrome - a rare cause of congenital nephrotic syndrome.

PMID- 24944147
TI  - Hemophagocytic lymphohistiocytosis presenting as subacute meningoencephalitis.

PMID- 24944148
TI  - Apnea as a complication of intravenous immunoglobulin therapy in a neonate.

PMID- 24944149
TI  - Do not miss the eye in acute demyelinating encephalomyelitis.

PMID- 24944150
TI  - Manubrium-limited sternotomy decreases blood loss after aortic valve replacement
      surgery.
AB  - OBJECTIVES: Minimally invasive surgical approaches for aortic valve replacement
      (AVR) are growing in popularity in an attempt to decrease morbidity from
      conventional surgery. We have adopted a technique that divides only the manubrium
      and spares the body of the sternum. We sought to determine whether patients
      benefit from this less-invasive approach. METHODS: We retrospectively analysed
      our prospectively maintained database to review all isolated aortic valve
      replacements performed in an 18-month period from November 2011 to April 2013.
      RESULTS: One hundred and ninety-one patients were identified, 98 underwent
      manubrium-limited sternotomy (Mini-AVR) and 93 had a conventional median
      sternotomy (AVR). The two groups were well matched for preoperative variables and
      risk (mean logistic EuroSCORE mini-AVR 7.15 vs AVR 6.55, P = 0.47). Mean
      cardiopulmonary bypass and aortic cross-clamp times were 10 and 6 min longer,
      respectively, in the mini-AVR group (mean values 88 vs 78 min, P = 0.00040, and
      66 vs 60 min, P = 0.0078, respectively). Mini-AVR patients had significantly less
      postoperative blood loss, 332 vs 513 ml, P = 0.00021, and were less likely to
      require blood products (fresh-frozen plasma and platelets), 24 vs 36%, P = 0.042.
      Postoperative complications and length of stay were similar (discharge on or
      before Day 4; mini-AVR 15 vs AVR 8%, P = 0.17). Valve outcome (paravalvular leak
      mini-AVR 2 vs AVR 1%, P = 1.00) and survival (mini-AVR 99 vs AVR 97%, P = 0.36)
      were equal. CONCLUSIONS: A manubrium-limited approach maintains outcomes achieved
      for aortic valve replacement by conventional sternotomy while significantly
      reducing postoperative blood loss and transfusion of blood products.

PMID- 24944152
TI  - IgG4-related cholecystitis presenting as biliary malignancy: report of three
      cases.
AB  - An increased awareness of IgG4-related diseases has led to an escalation in the
      number of sites known to be involved by this fibroinflammatory disease. We report
      three cases of IgG4-related cholecystitis which were thought to represent biliary
      malignancies both clinically and radiographically. All three cases underwent
      surgery tailored towards presumed malignant neoplasms. Only following pathologic
      examination was the true nature of the disease identified. Recognition of the
      clinical, radiographic, and pathologic presentation of IgG4-related cholecystitis
      is essential for the consideration of this disease process prior to surgical
      management for suspected gallbladder malignancies. However, the pre-operative
      diagnosis remains challenging and extensive surgical intervention is often
      necessary given the distressing presentation of IgG4-related cholecystitis. 

PMID- 24944151
TI  - Perioperative blood transfusion is associated with decreased survival in patients
      undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma: a multi
      institutional study.
AB  - INTRODUCTION: In this multi-institutional study of patients undergoing
      pancreaticoduodenectomy for pancreatic adenocarcinoma, we sought to identify
      factors associated with perioperative transfusion requirement as well as the
      association between blood transfusion and perioperative and oncologic outcomes.
      METHODS: The surgical databases across six high-volume institutions were analyzed
      to identify patients who underwent pancreaticoduodenectomy for pancreatic
      adenocarcinoma from 2005 to 2010. For statistical analyses, patients were then
      stratified by transfusion volume according to whether they received 0, 1-2, or >2
      units of packed red blood cells. RESULTS: Among 697 patients identified, 42 %
      required blood transfusion. Twenty-three percent received 1-2 units, and 19 %
      received >2 units. Factors associated with an increased transfusion requirement
      included older age, heart disease, diabetes, longer operative time, higher blood
      loss, tumor size, and non-R0 margin status (all p < 0.05). The median disease
      free survival (13.8 vs. 18.3 months, p = 0.02) and overall survival (14.0 vs.
      21.0 months, p < 0.0001) durations of transfused patients were shorter than those
      of transfusion-free patients. Multivariate modeling identified intraoperative
      transfusion of >2 units (hazard ratio, 1.92, p = 0.009) and postoperative
      transfusions as independent factors associated with decreased disease-free
      survival. CONCLUSIONS: This multi-institutional study represents the largest
      series to date analyzing the effects of perioperative blood transfusion on
      patient outcomes following pancreaticoduodenectomy for pancreatic adenocarcinoma.
      While blood transfusion was not associated with increased rate of infectious
      complications, allogeneic blood transfusion did confer a negative impact on
      disease-free and overall survival.

PMID- 24944153
TI  - Systematic review of early surgery for chronic pancreatitis: impact on pain,
      pancreatic function, and re-intervention.
AB  - BACKGROUND: Surgical intervention has traditionally been reserved as the last
      management option for pain in chronic pancreatitis. Recently, there has been a
      call for surgery to be offered earlier in the disease process. The objectives of
      this review were to evaluate the effect of early surgery on postoperative pain,
      pancreatic function, and re-intervention rates in chronic pancreatitis. METHODS:
      A systematic literature search through EMBASE, Cochrane Review, and PubMed from
      January 1950 to January 2014 was conducted. Citations found in relevant papers
      are hand-searched. Data which could be pooled were analyzed using Revman (v5.2).
      Risk of bias analysis was conducted. RESULTS: Of the 2,886 potentially eligible
      studies identified, 11 studies met the inclusion criteria. There was large
      heterogeneity in the study designs, and studies were conducted over a lengthy
      time span. Seven studies examined pain, three studies examined pancreatic
      function, and three studies examined rates of re-intervention. Meta-analysis of
      the three studies with comparative raw data regarding complete pain relief showed
      that early surgery was associated with an increased likelihood of complete
      postoperative pain relief (RR = 1.67, 95% CI 1.09-2.56, p = 0.02). Early surgery
      was also associated with reduced risk of pancreatic insufficiency and low re
      intervention rates. CONCLUSIONS: Data from this study supports considering early
      surgery for pain management in patients with chronic pancreatitis, with the
      potential of a reduced risk of pancreatic insufficiency and the need for further
      intervention. Further prospective randomized studies are warranted comparing
      early surgery against conservative step-up approaches.

PMID- 24944154
TI  - TNF-alpha, IL-6, and IL-8 cytokines and their association with TNF-alpha-308 G/A
      polymorphism and postoperative sepsis.
AB  - INTRODUCTION: Early prediction of postoperative sepsis remains an enormous
      clinical challenge. Association of TNF-alpha-308 G/A polymorphism with sepsis
      remains controversial. We, therefore, investigated this polymorphism with serum
      levels of cytokines TNF-alpha, IL-6, and IL-8 in relation to development of
      sepsis following major gastrointestinal surgery. METHODS: Two hundred and thirty
      nine patients undergoing major gastrointestinal surgery were enrolled.
      Polymorphism was studied through the analysis of restriction fragments of Nco1
      digested DNA with the polymerase chain reaction. All patients were followed for 1
      month following surgery for evidence of sepsis. Levels of serum cytokines TNF
      alpha, IL-6, and IL-8 were measured preoperatively and postoperatively by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Forty-seven (19.66 %) patients
      developed postoperative sepsis. Patients with postoperative sepsis were
      significantly (p = 0.002) more likely to possess AA homozygous genotype with
      higher capacity to produce cytokines TNF-alpha (p < 0.0001), IL-6 (p < 0.0001),
      and IL-8 (p < 0.0001) as compared to other genotypes. When compared with patients
      carrying at least one G allele, the AA genotype was associated with a
      significantly higher probability (odds ratio (OR) = 4.17; p = 0.003; 95 %
      confidence interval (CI) = 1.5-11.48) of developing sepsis. Compared with the GG
      genotype, AA was associated with a significantly higher probability (OR = 5.18; p
      = 0.0008; 95 % CI = 1.82-14.76) of sepsis development. CONCLUSION: TNF-alpha-308
      G/A polymorphism is significantly associated with the development of
      postoperative sepsis and with increased expression of cytokines TNF-alpha, IL-6,
      and IL-8.

PMID- 24944155
TI  - Single-center experience with parastomal hernia repair using retromuscular mesh
      placement.
AB  - BACKGROUND: Parastomal hernias (PHs) are frequent complications of enterostomies.
      We aimed to evaluate our outcomes of open PH repair with retromuscular mesh
      reinforcement. METHODS: From 2006 to 2013, 48 parastomal hernias were repaired in
      46 consecutive patients undergoing open retromuscular repair. Surgical technique
      included stoma relocation, retromuscular dissection, posterior component
      separation, and retromuscular mesh placement. All stomas were prophylactically
      reinforced with cruciate incisions through mesh. Main outcome measures included
      demographics, perioperative details, wound complications (classified according to
      the CDC guidelines), and recurrences. RESULTS: There were 24 male and 22 female
      patients with a mean age of 61.8 and body mass index (BMI) of 31.7 kg/m(2).
      Twenty-four patients had recurrent PH with an average of 3.8 prior repairs.
      Ostomies included 18 colostomies, 20 ileostomies, and 10 ileal conduits. Thirty
      two patients had a concurrent repair of a midline incisional hernia. All patients
      underwent mesh repair with either biologic (n = 29), lightweight polypropylene (n
      = 15), or absorbable synthetic mesh (n = 2). There were 15 superficial surgical
      site infections (SSIs) and 6 deep SSIs. There was one case of an ischemic ostomy
      requiring surgical revision. No mesh grafts required removal and there were no
      mesh erosions. At a mean follow-up time of 13 months, five patients (11%)
      developed a recurrence; three patients required re-repair. CONCLUSION: In this
      largest series of complex open repairs with retromuscular mesh reinforcement and
      stoma relocation, we demonstrate that this results in an effective repair. This
      technique should be considered for complex parastomal hernia repair.

PMID- 24944156
TI  - Subtotal gastrectomy with limited lymph node dissection is a feasible treatment
      option for patients with early gastric stump cancer.
AB  - The de facto standard treatment for early gastric stump cancer (GSC) has been
      total gastrectomy combined with radical lymph node dissection. However, some
      patients could benefit if partial resection of the gastric stump is feasible. We
      investigated the feasibility of subtotal gastrectomy for early GSC as less
      invasive surgery. Subtotal gastrectomy was defined as a segmental resection of
      the gastric remnant including the anastomosis with limited lymph node dissection.
      A total of 66 patients with early GSC were enrolled and 24 patients (36.4 %)
      underwent subtotal gastrectomy (SG group). Clinicopathological characteristics
      were analyzed along with those of the other 42 patients (63.6 %) who underwent
      total gastrectomy (TG group). There were no significant differences between the
      two groups in the number of lymph nodes harvested (p = 0.880). Lymph node
      involvement was detected in 2 patients (8.3 %) in SG group and 5 patients (11.9
      %) in TG group (p = 1.000). The previous disease (benign or malignant) and
      surgery (Billroth I or II) did not affect the rate of nodal involvement. The 5
      year overall survival rate of SG group (94.7 %) was acceptable. Subtotal
      gastrectomy of the gastric remnant could be a feasible treatment option for
      patients with early gastric stump cancer when indicated.

PMID- 24944157
TI  - Risk criteria for scientific researches. For whom the bell tolls?

PMID- 24944160
TI  - Development of an LC-MS/MS method for determination of bicalutamide on dried
      blood spots: application to pharmacokinetic study in mice.
AB  - A rapid and highly sensitive assay method has been developed and validated for
      the estimation of bicalutamide (BCL) on mouse dried blood spots (DBS) using
      liquid chromatography coupled to tandem mass spectrometry with electrospray
      ionization in the negative-ion mode. The assay procedure involves a simple liquid
      extraction of BCL and tolbutamide (internal standard, IS) from mouse blood DBS
      cards using tert-butyl methyl ether. Chromatographic separation was achieved with
      5 mm ammonium acetate (pH 6.5)-acetonitrile (35:65, v/v) at a flow rate of 0.60
      mL/min on an Atlantis dC18 column with a total run time 3.0 min. The MS/MS ion
      transitions monitored were 428.80 -> 254.70 for BCL and 269.00 -> 169.60 for IS.
      Method validation was performed as per regulatory guidelines. A linear response
      function was observed from 0.92 to 1911 ng/mL for BCL in mouse blood. The intra-
      and inter-day precisions were in the ranges of 1.86-12.5 and 3.19-10.8%,
      respectively. This novel DBS method has been applied to a pharmacokinetic study
      in mice.

PMID- 24944158
TI  - Interrelations between translation and general mRNA degradation in yeast.
AB  - Messenger RNA (mRNA) degradation is an important element of gene expression that
      can be modulated by alterations in translation, such as reductions in initiation
      or elongation rates. Reducing translation initiation strongly affects mRNA
      degradation by driving mRNA toward the assembly of a decapping complex, leading
      to decapping. While mRNA stability decreases as a consequence of translational
      inhibition, in apparent contradiction several external stresses both inhibit
      translation initiation and stabilize mRNA. A key difference in these processes is
      that stresses induce multiple responses, one of which stabilizes mRNAs at the
      initial and rate-limiting step of general mRNA decay. Because this increase in
      mRNA stability is directly induced by stress, it is independent of the
      translational effects of stress, which provide the cell with an opportunity to
      assess its response to changing environmental conditions. After assessment, the
      cell can store mRNAs, reinitiate their translation or, alternatively, embark on a
      program of enhanced mRNA decay en masse. Finally, recent results suggest that
      mRNA decay is not limited to non-translating messages and can occur when
      ribosomes are not initiating but are still elongating on mRNA. This review will
      discuss the models for the mechanisms of these processes and recent developments
      in understanding the relationship between translation and general mRNA
      degradation, with a focus on yeast as a model system.

PMID- 24944159
TI  - Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed
      chronic phase chronic myeloid leukemia.
AB  - Bosutinib, an orally active, Src/Abl tyrosine kinase inhibitor, has demonstrated
      clinical activity and acceptable tolerability in chronic phase chronic myeloid
      leukemia (CP CML). This updated analysis of the BELA trial assessed the safety
      profile and management of toxicities of bosutinib versus imatinib in adults with
      newly diagnosed (<=6 months) CP CML after >30 months from accrual completion.
      Among patients randomized to bosutinib 500 mg/d (n = 250) or imatinib 400 mg/d (n
      = 252), 248 and 251, respectively, received >=1 dose of study treatment. Adverse
      events (AEs; any grade) with bosutinib versus imatinib were significantly more
      common for certain gastrointestinal events (diarrhea, 70% vs. 26%; P < 0.001;
      vomiting, 33% vs. 16%; P < 0.001), alanine aminotransferase (33% vs. 9%; P <
      0.001) and aspartate aminotransferase (28% vs. 10%; P < 0.001) elevations, and
      pyrexia (19% vs. 12%; P = 0.046). AEs significantly less common with bosutinib
      included edema (periorbital, 2% vs. 14%; P < 0.001; peripheral, 5% vs. 12%; P =
      0.006), musculoskeletal (myalgia, 5% vs. 12%; P = 0.010; muscle cramps, 5% vs.
      22%; P < 0.001; bone pain, 4% vs. 11%; P = 0.003), increased creatine
      phosphokinase (8% vs. 20%; P < 0.001), neutropenia (13% vs. 30%; P < 0.001), and
      leukopenia (9% vs. 22%; P < 0.001). Between-group differences in the incidence of
      cardiac and vascular AEs were not significant. Diarrhea was typically transient,
      mostly Grade 1/2, occurring early during treatment, and was manageable with
      antidiarrheal medication. Despite higher rates of aminotransferase elevation with
      bosutinib, events were managed in most patients with dose modification and/or
      concomitant medication. Bosutinib had a manageable safety profile distinct from
      that of imatinib in patients with newly diagnosed CP CML.

PMID- 24944162
TI  - Predicting Reading Difficulty in First Grade Using Dynamic Assessment of Decoding
      in Early Kindergarten: A Large-Scale Longitudinal Study.
AB  - The purpose of this study was to examine and compare the classification accuracy
      of early static prereading measures and early dynamic assessment reading measures
      administered to 600 kindergarten students. At the beginning of kindergarten, all
      of the participants were administered two commonly used static prereading
      measures. The participants were then administered either a dynamic assessment
      featuring an onset-rime decoding strategy or a dynamic assessment featuring a
      sound-by-sound strategy. At the end of first grade, those same participants'
      reading ability was assessed using multiple reading measures. Results indicated
      that the dynamic assessments yielded significantly higher classification accuracy
      over the static measures, but that the classification accuracy of the two dynamic
      assessments did not differ significantly. Sensitivity for the static measures was
      less than 80%, and specificity ranged from 33% to 51%. The sensitivity and
      specificity for the dynamic assessments was greater than 80% for all children,
      with the exception of specificity for the Hispanic children, which was at or
      greater than 70%. Results also indicated that the combination of static and
      dynamic measures did not improve the classification accuracy over the dynamic
      assessments alone. Dynamic assessment appears to be a promising approach to
      classifying young children at risk for future reading difficulty. 

PMID- 24944163
TI  - Examining the Efficacy of a Tier 2 Kindergarten Mathematics Intervention.
AB  - This study examined the efficacy of a Tier 2 kindergarten mathematics
      intervention program, ROOTS, focused on developing whole number understanding for
      students at risk in mathematics. A total of 29 classrooms were randomly assigned
      to treatment (ROOTS) or control (standard district practices) conditions.
      Measures of mathematics achievement were collected at pretest and posttest.
      Treatment and control students did not differ on mathematics assessments at
      pretest. Gain scores of at-risk intervention students were significantly greater
      than those of control peers, and the gains of at-risk treatment students were
      greater than the gains of peers not at risk, effectively reducing the achievement
      gap. Implications for Tier 2 mathematics instruction in a response to
      intervention (RtI) model are discussed. 

PMID- 24944164
TI  - Religion and Subjective Well-Being: Western and Eastern Religious Groups Achieved
      Subjective Well-Being in Different Ways.
AB  - Culture can moderate which variables most influence subjective well-being (SWB).
      Because religion can be conceptualized as culture, religious differences can be
      considered cultural differences. However, there have been few studies comparing
      how different religious groups evaluate SWB at any given time. This study is
      among the first to investigate this issue. The present study compared Buddhists,
      Taoists, Christians, and atheists. In addition to demographic items, 451 Chinese
      adults completed Chinese version of the Socially Oriented Cultural Conception of
      SWB Scale. Religious belief was distributed as follows: 10 % Christian, 20 %
      Buddhist, 25 % Taoist, and 43 % atheists. As predicted, the socially oriented
      cultural conception of SWB was found to be highest among Buddhists, followed in
      order by Taoists, atheists, and Christians. It was concluded that the various
      religious groups achieved SWB in different ways. 

PMID- 24944161
TI  - Genome-wide hypermethylation coupled with promoter hypomethylation in the
      chorioamniotic membranes of early onset pre-eclampsia.
AB  - Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality.
      Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal
      outcomes, whilst its etiology is poorly understood. We hypothesize that
      epigenetics plays an important role to mediate the development of EOPE and
      conducted a case-control study to compare the genome-wide methylome difference
      between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using
      the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis
      tested differential methylation (DM) at CpG site level, gene level, and pathway
      and network level. A striking genome-wide hypermethylation pattern coupled with
      hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed
      DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over
      900 genes had DM associated with promoters. Promoter-based DM analysis revealed
      that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt,
      NFkappaB and ErBB4 were enriched, and represented biological functional
      alterations that involve cell cycle, apoptosis, cancer signaling and
      inflammation. A group of genes previously found to be up-regulated in pre
      eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits
      (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a
      cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329,
      mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their
      promoters in the EOPE samples. These findings collectively reveal new avenues of
      research regarding the vast epigenetic modifications in EOPE. 

PMID- 24944165
TI  - Religious/spiritual characteristics of indian and indonesian physicians and their
      acceptance of spirituality in health care: a cross-cultural comparison.
AB  - Religious/spiritual (r/s) characteristics of physicians influence their attitude
      toward integrative medicine and spiritual care. Indonesia physicians collaborate
      with traditional, complementary, and alternative medicine (TCAM) professionals
      within modern healthcare system, while Indian physicians are not reported to do
      so. The aim of the study was to understand the r/s characteristics and their
      influence on Indian and Indonesian physicians' acceptance of TCAM/spirituality in
      modern healthcare system. An exploratory, pilot, cross-cultural, cross-sectional
      study, using Religion and Spirituality in Medicine, and Physician Perspectives
      (RSMPP) survey questionnaire, compared r/s characteristics and perspectives on
      integrative medicine of 169 physicians from two allopathic, Sweekar-Osmania
      University (Sweekar-OU), India, University of Airlanga (UNAIR), Indonesia, and a
      TCAM/Central Research Institute of Unani Medicine (CRIUM) institute from India.
      More physicians from UNAIR and CRIUM (89.1 %) described themselves as
      "very"/"moderately" religious, compared to 63.5 % Sweekar-OU (p = 0.0000).
      Greater number of (84.6 %) UNAIR physicians described themselves as "very"
      spiritual and also significantly high (p < 0.05) in intrinsic religiosity as
      compared to Sweekar-OU and TCAM physicians; 38.6 % of UNAIR and 32.6 % of CRIUM
      participants reported life-changing spiritual experiences in clinical settings as
      against 19.7 % of Sweekar-OU; 92.3 % of UNAIR, compared to CRIUM (78.3 %) and
      Sweekar-OU (62 %), felt comfortable attending to patients' spiritual needs, (p =
      0.0001). Clinical comfort and not r/s characteristics of participants was the
      significant (p = 0.05) variable in full regression models, predictive of primary
      outcome criteria; "TCAM or r/s healing as complementary to allopathic treatment."
      In conclusion, mainstreaming TCAM into healthcare system may be an initial step
      toward both integrative medicine and also improving r/s care interventions by
      allopathic physicians.

PMID- 24944167
TI  - From the editor's perspective ....

PMID- 24944166
TI  - Intrinsically germanium-69-labeled iron oxide nanoparticles: synthesis and in
      vivo dual-modality PET/MR imaging.
AB  - Intrinsically germanium-69-labeled super-paramagnetic iron oxide nanoparticles
      are synthesized via a newly developed, fast and highly specific chelator-free
      approach. The biodistribution pattern and the feasibility of (69) Ge-SPION@PEG
      for in vivo dual-modality positron emission tomography/magnetic resonance
      (PET/MR) imaging and lymph-node mapping are investigated, which represents the
      first example of the successful utilization of a (69) Ge-based agent for PET/MR
      imaging. 

PMID- 24944169
TI  - Cardiovascular risk in white coat hypertension: an evaluation of the ankle
      brachial index.
AB  - The aim in this study was to identify the cardiovascular risk in patients
      suffering from white coat hypertension (WCH) by determining the ankle brachial
      index (ABI) with an automatic oscillometric sphygmomanometer. The study was
      undertaken in a Brazilian city between August 2010 and June 2011. The study
      variables were age, ethnic origin, marital status, education level, profession,
      weight, height, waist circumference, arm and ankle blood pressure (BP), and ABI.
      Analysis of variance was used for repeated measures and Tukey's test for multiple
      comparisons of means. The linear relationship between systolic BP levels and
      ankle brachial indices was verified using Pearson's correlation coefficient.
      Results were expressed as mean values +/- standard errors of means, and
      differences were considered statistically significant when P < .05. Study
      participants were 135 subjects, including 37% normotensive, 37% hypertensive
      (HT), and 26% WCH patients. WCH individuals revealed intermediate risk in the
      analysis of the clinical variables. Alterations compatible with peripheral
      obstructive arterial disease and arterial calcification were observed only in the
      HT and WCH groups. These findings lead to the premise that WCH should not be
      viewed as a benign condition. The measurement of the ABI should be considered in
      the clinical approach of patients and professionals should use it as an
      instrument for cardiovascular risk assessment in routine health care delivery. 

PMID- 24944170
TI  - Are plant-based diets efficacious in lowering total serum cholesterol and low
      density lipoprotein levels?
AB  - Cardiovascular disease is a leading cause of morbidity and mortality in the U.S.
      and around the globe. A large body of literature accumulated over the past
      several decades has shown the benefit of lowering serum total cholesterol (TC)
      and low-density lipoprotein cholesterol (LDL-C) levels to reduce cardiovascular
      risk. National guidelines suggest therapeutic lifestyle changes, beginning with
      diet, as a first step toward lowering TC and LDL-C. It has been suggested a plant
      based, low fat diet can substantially reduce TC and LDL- C and thereby reduce
      risk of cardiovascular disease. The purpose of this review is to examine the
      state of the science regarding the efficacy of plant-based diets in reducing
      serum TC and LDL-C levels. While results of the research review indicate some
      benefit, strong evidence supporting the efficacy of plant-based diet in reducing
      atherogenic lipids is lacking. 

PMID- 24944171
TI  - Training improves walking capacity and cardiovascular function in arteritis.
AB  - Patients with arteritis have a high risk of mortality from cardiovascular
      disorders. However, whether these patients benefit from an intervention involving
      exercise remains unclear. In this study, we assessed the effects of an
      unsupervised exercise program on walking capacity, quality of life, and
      cardiovascular parameters of a patient with arteritis. A 33-year-old man
      reporting symptoms of claudication during walking was studied. Imaging tests
      revealed severe atherosclerosis and arteritis was diagnosed. Five weekly sessions
      of walking for 16 weeks increased claudication distance and total walking
      distance, produced improvements in six out of the eight health-related quality-of
      life domains, decreased systolic blood pressure, and changed cardiac autonomic
      modulation toward parasympathetic modulation. This case report showed that
      unsupervised exercise training improved walking capacity, quality of life, and
      cardiovascular parameters in a patient with arteritis. 

PMID- 24944172
TI  - Predictors of pressure ulcer development in patients with vascular disease.
AB  - BACKGROUND: Although pressure ulcer (PU) risk factors are well known in the
      general population, little research is available in hospitalized surgical
      patients admitted with vascular diseases. METHODS: Using a retrospective medical
      records review, characteristics of hospitalized surgical patients with vascular
      diseases were assessed. Variables were based on literature review of PUs and
      availability of medical records and administrative data. Trained registered
      nurses collected data. Analyses included descriptive and comparative statistics,
      and multivariable modeling was used to determine predictors of PU. RESULTS: In
      849 adult admissions, 18.9% had a PU; 11.8% were hospital-acquired PU (HAPU).
      Patients were more likely to be elderly, male (n = 575; 67.7%), and Caucasian (n
      = 704; 83.3%). Common diagnoses were aneurysms/embolisms (43.2%) and
      atherosclerosis (31.2%). Patients with HAPU were more likely to be discharged to
      a skilled nursing or other facility compared with home (P < .001). In univariate
      analyses, 12 patient characteristics were associated with HAPU presence: Female
      gender, non-married status, current smoker, non-Caucasian race, non-intensive
      care unit (ICU) stay, primary diagnosis of atherosclerosis, higher analgesic use,
      higher right ankle brachial index (ABI), lower Braden score, higher blood urea
      nitrogen (BUN) higher serum creatinine and higher total protein levels. In
      multivariate analyses, nine factors predicted HAPU: Lower right ABI and Braden
      score, an ICU stay, low and high hematocrit values, female gender, non-White
      race, atherosclerosis history, and higher BUN and body mass index (BMI). The
      concordance index for the nine-item model was 0.854. CONCLUSION: The rate of HAPU
      in hospitalized surgical patients with vascular diseases was greater than
      expected. Assessment of important HAPU factors and implementation of
      interventions are needed to decrease risk and improve clinical outcomes.

PMID- 24944173
TI  - Endovascular repair of thoracic aortic pathologies: postoperative nursing
      implications.
AB  - Endovascular stent grafting is increasingly used to manage descending thoracic
      aortic pathologies. The procedure was introduced at the study hospital in 2001.
      We sought to examine the short-term clinical outcomes of patients who underwent
      this endovascular stent grafting, with the aim of using the result as baseline
      for development of an in-center clinical management protocol. We undertook a
      single-center, retrospective review of health care records of patients managed
      with thoracic stent grafts from 2001 to 2009. Patient characteristics, in
      hospital data, and procedural data were obtained. SPSS was used to analyze the
      data. A total of 30 patients were treated with thoracic stent; 23 were male, 7
      were female, and the mean age was 55.0. Aortic pathologies treated were traumatic
      aortic dissection/transection (n = 15), acute/chronic aortic dissection (n = 9),
      and degenerative aneurysms (n = 6). Endoleak occurred in 3 patients, with 1
      requiring further endograft repair. Two patients underwent combined open and
      endovascular repair of acute thoracic aortic dissection; 1 died 4 days after the
      procedure, and the other developed stroke and acute renal failure not requiring
      dialysis. Of the 28 patients who underwent endovascular repair, paraplegia and
      paraparesis occurred in 2 patients but resolved with cerebrospinal fluid
      drainage. Stroke occurred in 1 patient. Patients who underwent combined procedure
      of open and endovascular repair of thoracic aortic dissection had a greater risk
      of developing major adverse events than patients who underwent endovascular
      repair alone (Fisher's exact test P = .023). There was no association between the
      risk of stroke and the coverage of left subclavian artery in this series (P =
      .483). Graft stenting treatment for descending thoracic aortic pathologies has
      been shown to result in high in-hospital survival rates. It is essential for
      nurses who work in acute care settings to have knowledge of this procedure and
      potential complications associated with the procedure to enable postoperative
      assessment and immediate action if any deviation is observed. 

PMID- 24944174
TI  - Review of article: Effects of fluid resuscitation with colloids versus
      crystalloids on mortality in critically ill patients presenting with hypovolemic
      shock the CRISTAL randomized trial by Djillali Annane, Shidasp Siami, Samir
      Jaber, et al (JAMA 2013;310:1809-17).

PMID- 24944186
TI  - High-efficiency fluorescent organic light-emitting devices using sensitizing
      hosts with a small singlet-triplet exchange energy.
AB  - Materials with small singlet-triplet splits (DeltaEST s) are introduced as
      sensitizing hosts to excite fluorescent dopants, breaking the trade-off between
      small DeltaEST and high radiative decay rates. A highly efficient orange
      fluorescent organic light-emitting diode (OLED) is prepared, showing a maximum
      external quantum efficiency of 12.2%. 

PMID- 24944185
TI  - Development of realistic environmental release factors based on measured data:
      approach and lessons from the EU metal industry.
AB  - The assessment of environmental exposure and risks associated with the production
      or use of a substance on an industrial site includes the estimation of the
      releases to the environment. In the absence of measured release data on the
      specific substance, a risk assessor would rely on default release factors to the
      environmental compartments as developed in international, national, or regional
      context. Because a wide variety of substances, processes, and uses has to be
      covered, default release factors are as a rule conservative, usually leading to
      significant overprediction of releases and hence to overpredicted environmental
      exposure concentrations and risks. In practice, unrealistic and worst-case
      predictions do not support a more efficient management of releases and risk. The
      objective of this article is to propose a more realistic approach to characterize
      the environmental releases from manufacture, processing, and downstream uses of
      the metals and their compounds. Although developed in the European Union (EU),
      this approach can also be used in other regions and in other chemical management
      systems addressing metals. A database consisting of more than 1300 recent (1993
      2010), site-specific measured release factors to air and water of 18 different
      metals from various EU Member States was compiled and used to calculate average
      and reasonable worst-case release factors for multiple metal manufacture and
      industrial use processes. The parameters influencing releases to water were found
      to depend predominantly on life cycle step (manufacture and/or use), the sector
      and/or the solid-water partition coefficient (K(d)). The release factors can be
      used as advanced tier instrument in environmental safety assessments, increasing
      the realism of the estimates while still keeping a sufficient level of
      conservatism.

PMID- 24944187
TI  - Poor sleep quality in systemic lupus erythematosus: does it depend on depressive
      symptoms?
AB  - OBJECTIVES: Sleep disturbances are frequently observed in rheumatic diseases
      including systemic lupus erythematosus (SLE). This study aimed at evaluating the
      prevalence of insomnia, poor sleep quality and their determinants in a cohort of
      SLE patients. METHODS: Eighty-one consecutive SLE female patients were evaluated
      in a cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI), the
      Insomnia Severity Index (ISI), the Beck Depression Inventory (BDI) and the Self
      rating Anxiety Scale (SAS) were administered. Patients with previous diagnosis of
      obstructive sleep apnea or restless legs syndrome were excluded. Fifty-three
      women with hypertension (without SLE) were enrolled as control group (H).
      RESULTS: In the SLE cohort poor sleep quality (65.4% vs 39.6%, p < 0.01) and
      difficulty in maintaining sleep and/or early morning awakening (65.4% vs 22.6%, p
      < 0.001), but not insomnia (33.3% vs 22.6%, p = ns), were more prevalent than in
      H. Depressive symptoms were present in 34.6% of SLE vs 13.2% H patients (p <
      0.001) while state anxiety was more common in H patients (H 35.8% vs SLE 17.3%, p
      < 0.005). SLE was associated with a 2.5-times higher probability of presenting
      poor sleep quality in comparison to H (OR 2.5 [CI 1.21-5.16]). After adjusting
      for confounders, both depressive symptoms (OR 4.4, [1.4-14.3]) and use of
      immunosuppressive drugs (OR 4.3 [CI 1.3-14.8]) were significantly associated with
      poor sleep quality in SLE patients. Furthermore, poor sleep quality was not
      associated either with disease duration or activity. CONCLUSIONS: In a cohort of
      SLE women, insomnia and poor sleep quality, especially difficulties in
      maintaining sleep, were common. Depressive symptoms might be responsible for the
      higher prevalence of poor sleep quality in SLE.

PMID- 24944190
TI  - Parallel discovery of Alzheimer's therapeutics.
AB  - As the prevalence of Alzheimer's disease (AD) grows, so do the costs it imposes
      on society. Scientific, clinical, and financial interests have focused current
      drug discovery efforts largely on the single biological pathway that leads to
      amyloid deposition. This effort has resulted in slow progress and disappointing
      outcomes. Here, we describe a "portfolio approach" in which multiple distinct
      drug development projects are undertaken simultaneously. Although a greater
      upfront investment is required, the probability of at least one success should be
      higher with "multiple shots on goal," increasing the efficiency of this
      undertaking. However, our portfolio simulations show that the risk-adjusted
      return on investment of parallel discovery is insufficient to attract private
      sector funding. Nevertheless, the future cost savings of an effective AD therapy
      to Medicare and Medicaid far exceed this investment, suggesting that government
      funding is both essential and financially beneficial.

PMID- 24944188
TI  - Analyses of CD20 monoclonal antibody-mediated tumor cell killing mechanisms:
      rational design of dosing strategies.
AB  - Since approval of rituximab for treatment of B cell non-Hodgkin lymphoma,
      development of monoclonal antibodies (mAbs) for cancer treatment and elucidation
      of their cytotoxic mechanisms have been subject to intense investigations.
      Compelling evidence indicates that rituximab and another CD20 mAb, ofatumumab,
      must use the body's cellular and humoral immune effector functions to kill
      malignant cells. Other U.S. Food and Drug Administration-approved mAbs, including
      obinutuzumab, cetuximab, and trastuzumab, require, in part, these effector
      mechanisms to eliminate tumor cells. Although gram quantities of mAbs can be
      administered to patients, our investigations of CD20 mAb-based therapies for
      chronic lymphocytic leukemia (CLL), including correlative measurements in
      clinical trials and studies with primary cells and cell lines, indicate that
      effector mechanisms necessary for mAb activity can be saturated or exhausted if
      tumor burdens are high, thus substantially compromising the efficacy of high-dose
      mAb therapy. Under these conditions, another reaction (trogocytosis) predominates
      in which bound CD20 mAb and CD20 are removed from targeted cells by effector
      cells that express Fcgamma receptors, thereby allowing malignant cells to escape
      unharmed and continue to promote disease pathology. To address this problem, we
      propose that a low-dose strategy, based on administering 30-50 mg of CD20 mAb
      three times per week, may be far more effective for CLL than standard dosing
      because it will minimize effector function saturation and reduce trogocytosis.
      This approach may have general applicability to other mAbs that use immune
      effector functions, and could be formulated into a subcutaneous treatment
      strategy that would be more accessible and possibly more efficacious for
      patients. 

PMID- 24944189
TI  - Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5
      channels by ML213 and ICA-069673.
AB  - Recent research suggests that smooth muscle cells express Kv7.4 and Kv7.5 voltage
      activated potassium channels, which contribute to maintenance of their resting
      membrane voltage. New pharmacologic activators of Kv7 channels, ML213 (N
      mesitybicyclo[2.2.1]heptane-2-carboxamide) and ICA-069673 N-(6-chloropyridin-3
      yl)-3,4-difluorobenzamide), have been reported to discriminate among channels
      formed from different Kv7 subtypes. We compared the effects of ML213 and ICA
      069673 on homomeric human Kv7.4, Kv7.5, and heteromeric Kv7.4/7.5 channels
      exogenously expressed in A7r5 vascular smooth muscle cells. We found that,
      despite its previous description as a selective activator of Kv7.2 and Kv7.4,
      ML213 significantly increased the maximum conductance of homomeric Kv7.4 and
      Kv7.5, as well as heteromeric Kv7.4/7.5 channels, and induced a negative shift of
      their activation curves. Current deactivation rates decreased in the presence of
      the ML213 (10 MUM) for all three channel combinations. Mutants of Kv7.4 (W242L)
      and Kv7.5 (W235L), previously found to be insensitive to another Kv7 channel
      activator, retigabine, were also insensitive to ML213 (10 MUM). In contrast to
      ML213, ICA-069673 robustly activated Kv7.4 channels but was significantly less
      effective on homomeric Kv7.5 channels. Heteromeric Kv7.4/7.5 channels displayed
      intermediate responses to ICA-069673. In each case, ICA-069673 induced a negative
      shift of the activation curves without significantly increasing maximal
      conductance. Current deactivation rates decreased in the presence of ICA-069673
      in a subunit-specific manner. Kv7.4 W242L responded to ICA-069673-like wild-type
      Kv7.4, but a Kv7.4 F143A mutant was much less sensitive to ICA-069673. Based on
      these results, ML213 and ICA-069673 likely bind to different sites and are
      differentially selective among Kv7.4, Kv7.5, and Kv7.4/7.5 channel subtypes. 

PMID- 24944191
TI  - Chronic diseases in HIV survivors.

PMID- 24944192
TI  - Circulating cell-free DNA enables noninvasive diagnosis of heart transplant
      rejection.
AB  - Monitoring allograft health is an important component of posttransplant therapy.
      Endomyocardial biopsy is the current gold standard for cardiac allograft
      monitoring but is an expensive and invasive procedure. Proof of principle of a
      universal, noninvasive diagnostic method based on high-throughput screening of
      circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a
      small retrospective cohort. We present the results of a prospective cohort study
      (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute
      rejection after heart transplantation. Circulating cell-free DNA was purified
      from plasma and sequenced (mean depth, 1.2 giga-base pairs) to quantify the
      fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we
      demonstrate that cfdDNA enables diagnosis of acute rejection after heart
      transplantation, with an area under the receiver operating characteristic curve
      of 0.83 and sensitivity and specificity that are comparable to the intrinsic
      performance of the biopsy itself. This noninvasive genome transplant dynamics
      approach is a powerful and informative method for routine monitoring of allograft
      health without incurring the risk, discomfort, and expense of an invasive biopsy.

PMID- 24944193
TI  - In vivo-generated antigen-specific regulatory T cells treat autoimmunity without
      compromising antibacterial immune response.
AB  - Harnessing regulatory T (Treg) cells is a promising approach for treating
      autoimmune disease. However, inducing antigen-specific Treg cells that target
      inflammatory immune cells without compromising beneficial immune responses has
      remained an unmet challenge. We developed a pathway to generate autoantigen
      specific Treg cells in vivo, which showed therapeutic effects on experimental
      autoimmune encephalomyelitis and nonobese diabetes in mice. Specifically, we
      induced apoptosis of immune cells by systemic sublethal irradiation or depleted B
      and CD8(+) T cells with specific antibodies and then administered autoantigenic
      peptides in mice with established autoimmune diseases. We demonstrated
      mechanistically that apoptotic cells triggered professional phagocytes to produce
      transforming growth factor-beta, under which the autoantigenic peptides directed
      naive CD4(+) T cells to differentiate into Foxp3(+) Treg cells instead of into T
      effector cells in vivo. These antigen-specific Treg cells specifically
      ameliorated autoimmunity without compromising immune responses to bacterial
      antigen. We have thus successfully generated antigen-specific Treg cells with
      therapeutic activity toward autoimmunity. The findings may lead to the
      development of antigen-specific Treg cell-mediated immunotherapy for multiple
      sclerosis and type 1 diabetes and also other autoimmune diseases.

PMID- 24944195
TI  - IL-17 and GM-CSF expression are antagonistically regulated by human T helper
      cells.
AB  - Although T helper 17 (TH17) cells have been acknowledged as crucial mediators of
      autoimmune tissue damage, the effector cytokines responsible for their
      pathogenicity still remain poorly defined, particularly in humans. In mouse
      models of autoimmunity, the pathogenicity of TH17 cells has recently been
      associated with their production of granulocyte-macrophage colony-stimulating
      factor (GM-CSF). We analyzed the regulation of GM-CSF expression by human TH cell
      subsets. Surprisingly, the induction of GM-CSF expression by human TH cells is
      constrained by the interleukin-23 (IL-23)/ROR-gammat/TH17 cell axis but promoted
      by the IL-12/T-bet/TH1 cell axis. IL-2-mediated signal transducer and activator
      of transcription 5 (STAT5) signaling induced GM-CSF expression in naive and
      memory TH cells, whereas STAT3 signaling blocked it. The opposite effect was
      observed for IL-17 expression. Ex vivo, GM-CSF(+) TH cells that coexpress
      interferon-gamma and T-bet could be distinguished by differential chemokine
      receptor expression from a previously uncharacterized subset of GM-CSF-only
      producing TH cells that did not express TH1, TH2, and TH17 signature cytokines or
      master transcription factors. Our findings demonstrate distinct and
      counterregulatory pathways for the generation of IL-17- and GM-CSF-producing
      cells and also suggest a pathogenic role for GM-CSF(+) T cells in the inflamed
      brain of multiple sclerosis (MS) patients. This provides not only a scientific
      rationale for depleting T cell-derived GM-CSF in MS patients but also multiple
      new molecular checkpoints for therapeutic GM-CSF suppression, which, unlike in
      mice, do not associate with the TH17 but instead with the TH1 axis.

PMID- 24944194
TI  - Selective targeting of TGF-beta activation to treat fibroinflammatory airway
      disease.
AB  - Airway remodeling, caused by inflammation and fibrosis, is a major component of
      chronic obstructive pulmonary disease (COPD) and currently has no effective
      treatment. Transforming growth factor-beta (TGF-beta) has been widely implicated
      in the pathogenesis of airway remodeling in COPD. TGF-beta is expressed in a
      latent form that requires activation. The integrin alphavbeta8 (encoded by the
      itgb8 gene) is a receptor for latent TGF-beta and is essential for its
      activation. Expression of integrin alphavbeta8 is increased in airway fibroblasts
      in COPD and thus is an attractive therapeutic target for the treatment of airway
      remodeling in COPD. We demonstrate that an engineered optimized antibody to human
      alphavbeta8 (B5) inhibited TGF-beta activation in transgenic mice expressing only
      human and not mouse ITGB8. The B5 engineered antibody blocked fibroinflammatory
      responses induced by tobacco smoke, cytokines, and allergens by inhibiting TGF
      beta activation. To clarify the mechanism of action of B5, we used hydrodynamic,
      mutational, and electron microscopic methods to demonstrate that alphavbeta8
      predominantly adopts a constitutively active, extended-closed headpiece
      conformation. Epitope mapping and functional characterization of B5 revealed an
      allosteric mechanism of action due to locking-in of a low-affinity alphavbeta8
      conformation. Collectively, these data demonstrate a new model for integrin
      function and present a strategy to selectively target the TGF-beta pathway to
      treat fibroinflammatory airway diseases.

PMID- 24944196
TI  - The value of heterogeneity for cost-effectiveness subgroup analysis: conceptual
      framework and application.
AB  - This article develops a general framework to guide the use of subgroup cost
      effectiveness analysis for decision making in a collectively funded health
      system. In doing so, it addresses 2 key policy questions, namely, the
      identification and selection of subgroups, while distinguishing 2 sources of
      potential value associated with heterogeneity. These are 1) the value of
      revealing the factors associated with heterogeneity in costs and outcomes using
      existing evidence (static value) and 2) the value of acquiring further subgroup
      related evidence to resolve the uncertainty given the current understanding of
      heterogeneity (dynamic value). Consideration of these 2 sources of value can
      guide subgroup-specific treatment decisions and inform whether further research
      should be conducted to resolve uncertainty to explain variability in costs and
      outcomes. We apply the proposed methods to a cost-effectiveness analysis for the
      management of patients with acute coronary syndrome. This study presents the
      expected net benefits under current and perfect information when subgroups are
      defined based on the use and combination of 6 binary covariates. The results of
      the case study confirm the theoretical expectations. As more subgroups are
      considered, the marginal net benefit gains obtained under the current information
      show diminishing marginal returns, and the expected value of perfect information
      shows a decreasing trend. We present a suggested algorithm that synthesizes the
      results to guide policy.

PMID- 24944197
TI  - Optimal antisense target reducing INS intron 1 retention is adjacent to a
      parallel G quadruplex.
AB  - Splice-switching oligonucleotides (SSOs) have been widely used to inhibit exon
      usage but antisense strategies that promote removal of entire introns to increase
      splicing-mediated gene expression have not been developed. Here we show reduction
      of INS intron 1 retention by SSOs that bind transcripts derived from a human
      haplotype expressing low levels of proinsulin. This haplotype is tagged by a
      polypyrimidine tract variant rs689 that decreases the efficiency of intron 1
      splicing and increases the relative abundance of mRNAs with extended 5'
      untranslated region (5' UTR), which curtails translation. Co-expression of
      haplotype-specific reporter constructs with SSOs bound to splicing regulatory
      motifs and decoy splice sites in primary transcripts revealed a motif that
      significantly reduced intron 1-containing mRNAs. Using an antisense microwalk at
      a single nucleotide resolution, the optimal target was mapped to a splicing
      silencer containing two pseudoacceptor sites sandwiched between predicted RNA
      guanine (G) quadruplex structures. Circular dichroism spectroscopy and nuclear
      magnetic resonance of synthetic G-rich oligoribonucleotide tracts derived from
      this region showed formation of a stable parallel 2-quartet G-quadruplex on the
      3' side of the antisense retention target and an equilibrium between quadruplexes
      and stable hairpin-loop structures bound by optimal SSOs. This region interacts
      with heterogeneous nuclear ribonucleoproteins F and H that may interfere with
      conformational transitions involving the antisense target. The SSO-assisted
      promotion of weak intron removal from the 5' UTR through competing noncanonical
      and canonical RNA structures may facilitate development of novel strategies to
      enhance gene expression. 

PMID- 24944199
TI  - Novel activators of aquaporin 2 membrane expression for the treatment of
      nephrogenic diabetes insipidus: less is more. Focus on "High-throughput chemical
      screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression
      and urine concentration".

PMID- 24944198
TI  - Specific inhibition of HDAC4 in cardiac progenitor cells enhances myocardial
      repairs.
AB  - We have recently shown that in vivo inhibition of histone deacetylase (HDAC)
      stimulates endogenous myocardial regeneration in infarcted hearts (Zhang L et al.
      J Pharmacol Exp Ther 341: 285-293, 2012). Furthermore, our observation
      demonstrates that HDAC inhibition promotes cardiogenesis, which is associated
      with HDAC4 reduction. However, it remains unknown as to whether specific
      inhibition of HDAC4 modulates cardiac stem cells (CSCs) to facilitate myocardial
      repair and to preserve cardiac performance. c-kit(+) CSCs were isolated from
      adult mouse hearts and were transfected with HDAC4 siRNA to knockdown HDAC4 of c
      kit(+) CSCs. The transfection of HDAC4 siRNA caused a marked reduction of HDAC4
      mRNA and proteins in c-kit(+) CSCs. Mouse myocardial infarction (MI) was created
      to assess the effect of HDAC4 inhibition in c-kit(+) CSCs on myocardial
      regeneration in vivo when cells were introduced into MI hearts. Transplantation
      of HDAC4 siRNA-treated c-kit(+) CSCs into MI hearts improved ventricular
      function, attenuated ventricular remodeling, and promoted CSC-derived
      regeneration and neovascularization. Furthermore, Ki67 and BrdU positively
      proliferative myocytes increased in MI hearts receiving HDAC4 siRNA-treated c
      kit(+) CSCs compared with MI hearts engrafted with control siRNA-treated c-kit(+)
      CSCs. In addition, compared with MI hearts engrafted with control adenoviral GFP
      infected c-kit(+) CSCs, MI hearts receiving adenoviral HDAC4-infected c-kit(+)
      CSCs exhibited attenuated cardiac functional recovery, CSC-derived regeneration,
      and neovascularization, which was accompanied with adverse ventricular remodeling
      and decrease in Ki67 and BrdU positively proliferative myocytes. HDAC4 inhibition
      facilitated c-kit(+) CSCs into the differentiation into cardiac lineage
      commitments in vitro, while HDAC4 overexpression attenuated c-kit(+) CSC-derived
      cardiogenesis. Our results indicate that HDAC4 inhibition promotes CSC-derived
      cardiac regeneration and improves the restoration of cardiac function. 

PMID- 24944200
TI  - High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin
      2 membrane expression and urine concentration.
AB  - A reduction or loss of plasma membrane aquaporin 2 (AQP2) in kidney principal
      cells due to defective vasopressin (VP) signaling through the VP receptor causes
      excessive urine production, i.e., diabetes insipidus. The amount of AQP2 on the
      plasma membrane is regulated by a balance of exocytosis and endocytosis and is
      the rate limiting step for water reabsorption in the collecting duct. We describe
      here a systematic approach using high-throughput screening (HTS) followed by in
      vitro and in vivo assays to discover novel compounds that enhance vasopressin
      independent AQP2 membrane expression. We performed initial chemical library
      screening with a high-throughput exocytosis fluorescence assay using LLC-PK1
      cells expressing soluble secreted yellow fluorescent protein and AQP2. Thirty-six
      candidate exocytosis enhancers were identified. These compounds were then
      rescreened in AQP2-expressing cells to determine their ability to increase AQP2
      membrane accumulation. Effective drugs were then applied to kidney slices in
      vitro. Three compounds, AG-490, beta-lapachone, and HA14-1 increased AQP2
      membrane accumulation in LLC-PK1 cells, and both AG-490 and beta-lapachone were
      also effective in MDCK cells and principal cells in rat kidney slices. Finally,
      one compound, AG-490 (an EGF receptor and JAK-2 kinase inhibitor), decreased
      urine volume and increased urine osmolality significantly in the first 2-4 h
      after a single injection into VP-deficient Brattleboro rats. In conclusion, we
      have developed a systematic procedure for identifying new compounds that modulate
      AQP2 trafficking using initial HTS followed by in vitro assays in cells and
      kidney slices, and concluding with in vivo testing in an animal model.

PMID- 24944203
TI  - The NADPH oxidase inhibitor diphenyleneiodonium activates the human TRPA1
      nociceptor.
AB  - Transient receptor potential ankyrin 1 (TRPA1) is a Ca(2+)-permeable nonselective
      cation channel expressed in neuronal and nonneuronal cells and plays an important
      role in acute and inflammatory pain. Here, we show that an NADPH oxidase (NOX)
      inhibitor, diphenyleneiodonium (DPI), functions as a TRPA1 activator in human
      embryonic kidney cells expressing human TRPA1 (HEK-TRPA1) and in human fibroblast
      like synoviocytes. Application of DPI at 0.03-10 MUM induced a Ca(2+) response in
      HEK-TRPA1 cells in a concentration-dependent manner. The Ca(2+) response was
      effectively blocked by a selective TRPA1 antagonist, HC-030031 (HC). In contrast,
      DPI had no effect on HEK cells expressing TRPV1-V4 or TRPM8. Four other NOX
      inhibitors, apocynin (APO), VAS2870 (VAS), plumbagin, and 2-acetylphenothiazine,
      also induced a Ca(2+) response in HEK-TRPA1 cells, which was inhibited by
      pretreatment with HC. In the presence of 5 mM glutathione, the Ca(2+) response to
      DPI was effectively reduced. Moreover, mutation of cysteine 621 in TRPA1
      substantially inhibited the DPI-induced Ca(2+) response, while it did not inhibit
      the APO- and VAS-induced responses. The channel activity was induced by DPI in
      excised membrane patches with both outside-out and inside-out configurations.
      Internal application of neomycin significantly inhibited the DPI-induced inward
      currents. In inflammatory synoviocytes with TRPA1, DPI evoked a Ca(2+) response
      that was sensitive to HC. In mice, intraplantar injection of DPI caused a pain
      related response which was inhibited by preadministration with HC. Taken
      together, our findings demonstrate that DPI and other NOX inhibitors activate
      human TRPA1 without mediating NOX. 

PMID- 24944201
TI  - ERp29 regulates epithelial sodium channel functional expression by promoting
      channel cleavage.
AB  - The epithelial Na(+) channel (ENaC) plays a key role in the regulation of blood
      pressure and airway surface liquid volume. ERp29 is a 29-kDa thioredoxin
      homologous endoplasmic reticulum (ER) protein that has only a single cysteine
      instead of the usual thioredoxin CXXC motif. Our group previously demonstrated
      that ERp29 promotes biogenesis of the cystic fibrosis transmembrane conductance
      regulator (CFTR). On the basis of similarities of CFTR and ENaC trafficking, we
      hypothesized that ERp29 would also regulate ENaC biogenesis and functional
      expression. In epithelial cells, overexpression of wild-type (wt) ERp29 increased
      ENaC functional expression [amiloride-sensitive short-circuit current (Isc)] in
      Ussing chamber experiments, as well as the abundance of the cleaved form of gamma
      ENaC in whole cell lysates. In contrast, siRNA-mediated depletion of ERp29 or
      overexpression of a mutant ERp29 lacking its single cysteine (C157S ERp29)
      decreased ENaC functional expression. Cells in which wt ERp29 was overexpressed
      had a smaller fractional increase in amiloride-sensitive Isc when trypsin was
      applied to the apical surface to activate uncleaved ENaC, while cells in which
      C157S ERp29 was overexpressed or ERp29 was depleted had a significantly greater
      fractional increase in amiloride-sensitive Isc in response to trypsin.
      Interestingly, these observations were not associated with altered expression of
      beta-ENaC at the apical surface. Instead, ERp29 appeared to promote the
      interaction of beta-ENaC with the Sec24D cargo recognition component of the coat
      complex II ER exit machinery. Together, these data support the hypothesis that
      ERp29 directs ENaC toward the Golgi, where it undergoes cleavage during its
      biogenesis and trafficking to the apical membrane. 

PMID- 24944202
TI  - Cytokine-induced iNOS and ERK1/2 inhibit adenylyl cyclase type 5/6 activity and
      stimulate phosphodiesterase 4D5 activity in intestinal longitudinal smooth
      muscle.
AB  - This study identified a distinctive pattern of expression and activity of
      adenylyl cyclase (AC) and phosphodiesterase (PDE) isoforms in mouse colonic
      longitudinal smooth muscle cells and determined the changes in their expression
      and/or activity in response to proinflammatory cytokines (IL-1beta and TNF-alpha)
      in vitro and 2,4,6 trinitrobenzene sulphonic acid (TNBS)-induced colonic
      inflammation in vivo. AC5/6 and PDE4D5, expressed in circular muscle cells, were
      also expressed in longitudinal smooth muscle. cAMP formation was tightly
      regulated via feedback phosphorylation of AC5/6 and PDE4D5 by PKA. Inhibition of
      PKA activity by myristoylated PKI blocked phosphorylation of AC5/6 and PDE4D5 and
      enhanced cAMP formation. TNBS treatment in vivo and IL-1beta and TNF-alpha in
      vitro induced inducible nitric oxide synthase (iNOS) expression, stimulated
      ERK1/2 activity, caused iNOS-mediated S-nitrosylation and inhibition of AC5/6,
      and induced phosphorylation of PDE4D5 and stimulated its activity. The resultant
      decrease in AC5/6 activity and increase in PDE4D5 activity decreased cAMP
      formation and smooth muscle relaxation. S-nitrosylation and inhibition of AC5/6
      activity were reversed by the iNOS inhibitor 1400W, whereas phosphorylation and
      activation of PDE4D5 were reversed by the phosphatidylinositol 3-kinase inhibitor
      LY294002 and the ERK1/2 inhibitor PD98059. The effects of IL-1beta or TNF-alpha
      on forskolin-stimulated cAMP formation and smooth muscle relaxation reflected
      inhibition of AC5/6 activity and activation of PDE4D5 and were partly reversed by
      1400W or PD98059 and completely reversed by a combination of the two inhibitors.
      The changes in the cAMP/PKA signaling and smooth muscle relaxation contribute to
      colonic dysmotility during inflammation. 

PMID- 24944204
TI  - The transport mechanism of the human sodium/myo-inositol transporter 2
      (SMIT2/SGLT6), a member of the LeuT structural family.
AB  - The sodium/myo-inositol transporter 2 (SMIT2) is a member of the SLC5A gene
      family, which is believed to share the five-transmembrane segment inverted repeat
      of the LeuT structural family. The two-electrode voltage-clamp (TEVC) technique
      was used to measure the steady-state and the pre-steady-state currents mediated
      by human SMIT2 after expression in Xenopus laevis oocytes. Phlorizin is first
      shown to be a poor inhibitor of pre-steady-state currents for depolarizing
      voltage pulse. From an up to threefold difference between the apparent ON and OFF
      transferred charges during a voltage pulse, we also show that a fraction of the
      transient current recorded for very negative potentials is not a true pre-steady
      state current coming from the cotransporter conformational changes. We suggest
      that this transient current comes from a time-dependent leak current that can
      reach large amplitudes when external Na(+) concentration is reduced. A kinetic
      model was generated through a simulated annealing algorithm. This algorithm was
      used to identify the optimal connectivity among 19 different kinetic models and
      obtain the numerical values of the associated parameters. The proposed 5-state
      model includes cooperative binding of Na(+) ions, strong apparent asymmetry of
      the energy barriers, a rate-limiting step that is likely associated with the
      translocation of the empty transporter, and a turnover rate of 21 s(-1). The
      proposed model is a proof of concept for a novel approach to kinetic modeling of
      electrogenic transporters and allows insight into the transport mechanism of
      members of the LeuT structural family at the millisecond timescale. 

PMID- 24944205
TI  - Cellular mechanisms of endoplasmic reticulum stress signaling in health and
      disease. 2. Protein misfolding and ER stress.
AB  - The endoplasmic reticulum (ER) is a major site of protein synthesis, most
      strikingly in the specialized secretory cells of metazoans, which can produce
      their own weight in proteins daily. Cells possess a diverse machinery to ensure
      correct folding, assembly, and secretion of proteins from the ER. When this
      machinery is overwhelmed, the cell is said to experience ER stress, a result of
      the accumulation of unfolded or misfolded proteins in the lumen of the organelle.
      Here we discuss the causes of ER stress and the mechanisms by which cells elicit
      a response, with an emphasis on recent discoveries. 

PMID- 24944207
TI  - Stem cells and religion.

PMID- 24944206
TI  - Concise review: diabetes, the bone marrow niche, and impaired vascular
      regeneration.
AB  - Diabetes mellitus is a global health problem that results in multiorgan
      complications leading to high morbidity and mortality. Until recently, the
      effects of diabetes and hyperglycemia on the bone marrow microenvironment-a site
      where multiple organ systems converge and communicate-have been underappreciated.
      However, several new studies in mice, rats, and humans reveal that diabetes leads
      to multiple bone marrow microenvironmental defects, such as small vessel disease
      (microangiopathy), nerve terminal pauperization (neuropathy), and impaired stem
      cell mobilization (mobilopathy). The discovery that diabetes involves bone marrow
      derived progenitors implicated in maintaining cardiovascular homeostasis has been
      proposed as a bridging mechanism between micro- and macroangiopathy in distant
      organs. Herein, we review the physiological and molecular bone marrow
      abnormalities associated with diabetes and discuss how bone marrow dysfunction
      represents a potential root for the development of the multiorgan failure
      characteristic of advanced diabetes. The notion of diabetes as a bone marrow and
      stem cell disease opens new avenues for therapeutic interventions ultimately
      aimed at improving the outcome of diabetic patients. 

PMID- 24944208
TI  - In vivo hypobaric hypoxia performed during the remodeling process accelerates
      bone healing in mice.
AB  - We investigated the effects of respiratory hypobaric hypoxia on femoral bone
      defect repair in mice because hypoxia is believed to influence both mesenchymal
      stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved
      in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb
      immobilization in patients suffering from bone trauma, our hypoxic mouse model
      was further subjected to hind-limb unloading. A hole was drilled in the right
      femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected
      to hind-limb unloading for 1 week. Seven days after surgery, mice were either
      housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic
      conditions. Unsuspended control mice were housed in either hypobaric or normoxic
      conditions. Animals were sacrificed on postsurgery day 11 to allow for collection
      of both contralateral and lesioned femurs, blood, and spleen. As assessed by
      microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing
      the closing of the cortical defect and the newly synthesized bone volume in the
      cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric
      data suggested that bone-repair improvement likely results from the acceleration
      of the natural bone-healing process rather than from extended mobilization of MSC
      derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond
      delayed hypoxia-enhanced bone-healing efficiency. 

PMID- 24944209
TI  - The impact of warfarin on the rate of progression of aortic stiffness in
      hemodialysis patients: a longitudinal study.
AB  - BACKGROUND: Accelerated progression of aortic stiffness in patients with advanced
      chronic kidney disease is not well explained by the traditional cardiovascular
      risk factors. We hypothesized that vitamin K deficiency may result in an
      accelerated progression of aortic stiffness in the pro-calcifying uremic milieu.
      METHOD: Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD
      patients without warfarin (control). Aortic stiffness was determined by carotid
      femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of
      1.2 years. In the control group, spontaneous vitamin K deficiency was defined as
      proteins induced by vitamin K deficiency/absence-II >median. RESULTS: At
      baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV
      increased by 0.86 +/- 1.87 m/s in control and by 2.24 +/- 2.68 m/s in warfarin
      group (P = 0.024). After adjustments for confounders, warfarin therapy was
      independently associated with progression of aortic stiffness (P = 0.016). The
      rate of progression of aortic stiffness showed a linear trend in response to
      vitamin K status and warfarin therapy, suggesting that at least part of the
      effects are mediated through reduced availability of vitamin K. The unadjusted
      and adjusted hazard ratio (HR) of warfarin therapy on mortality were,
      respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox
      regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8
      m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants
      of mortality, whereas warfarin use was not retained as an independent factor.
      Finally, control patients with poor vitamin K status had an intermediate survival
      as compared with controls with better vitamin K status and patients with warfarin
      (P = 0.01). CONCLUSION: This is the first study to show a temporal association
      between warfarin, functional vitamin K deficiency and progression of aortic
      stiffness in HD patients. These findings suggest that the net cardiovascular
      benefit of long-term warfarin therapy may need to be reevaluated in this
      population.

PMID- 24944210
TI  - The association between underweight and the development of albuminuria is
      different between sexes in relatively healthy Korean subjects.
AB  - BACKGROUND: There are limited data on the association between underweight and
      albuminuria. The aim of this study is to verify the effect of underweight on the
      development of albuminuria. METHODS: Participants who underwent two health check
      ups with a 2-year interval at a tertiary hospital in Korea between 2002 and 2009
      were studied. After exclusion of participants with estimated glomerular
      filtration rate (eGFR) <60 mL/min/1.73 m(2) or dipstick albuminuria >=1+ at the
      first check-up, 53 876 participants were enrolled. We measured the incidence of
      albuminuria at the second check-up and calculated the odds ratio (OR) for the
      development of albuminuria according to body mass index (BMI). RESULTS: After 2
      years, 746 cases of incident albuminuria were observed among 53 876 participants.
      The effect of BMI on the development of albuminuria was modified by sex in a
      multivariate logistic model with adjustment for age, diabetes, hypertension,
      dyslipidaemia, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, uric acid, eGFR, current smoking status and alcohol intake (P-value
      for interaction <0.001). Compared with participants in the normal weight range
      (BMI, 18.5-22.9), the ORs for incident albuminuria were 1.93 [95% confidence
      interval (CI), 1.35-2.76; P <= 0.001], 1.19 (0.84-1.67; P = 0.329) and 0.71 (0.43
      1.17; P = 0.177) in underweight (BMI, <18.5), overweight (BMI, 23.0-24.9) and
      obese (BMI, >=25) women. However, the ORs were 0.9 (95% CI, 0.39-2.05; P =
      0.794), 1.08 (0.84-1.38; P = 0.567) and 1.38 (1.09-1.75; P = 0.007) for each
      corresponding group of men. CONCLUSIONS: Underweight was significantly associated
      with the development of albuminuria after 2 years in relatively healthy Korean
      females, but this relationship was not significant in males. This study suggests
      the need for more studies on the role of underweight in renal injury in men and
      women.

PMID- 24944211
TI  - Synaptobrevin 1 mediates vesicle priming and evoked release in a subpopulation of
      hippocampal neurons.
AB  - The core machinery of synaptic vesicle fusion consists of three soluble N
      ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, the two t
      SNAREs at the plasma membrane (SNAP-25, Syntaxin 1) and the vesicle-bound v-SNARE
      synaptobrevin 2 (VAMP2). Formation of the trans-oriented four-alpha-helix bundle
      between these SNAREs brings vesicle and plasma membrane in close proximity and
      prepares the vesicle for fusion. The t-SNAREs are thought to be necessary for
      vesicle fusion. Whether the v-SNAREs are required for fusion is still unclear, as
      substantial vesicle priming and spontaneous release activity remain in mammalian
      mass-cultured synaptobrevin/cellubrevin-deficient neurons. Using the autaptic
      culture system from synaptobrevin 2 knockout neurons of mouse hippocampus, we
      found that the majority of cells were devoid of any evoked or spontaneous release
      and had no measurable readily releasable pool. A small subpopulation of neurons,
      however, displayed release, and their release activity correlated with the
      presence and amount of v-SNARE synaptobrevin 1 expressed. Comparison of
      synaptobrevin 1 and 2 in rescue experiments demonstrates that synaptobrevin 1 can
      substitute for the other v-SNARE, but with a lower efficiency in neurotransmitter
      release probability. Release activity in synaptobrevin 2-deficient mass-cultured
      neurons was massively reduced by a knockdown of synaptobrevin 1, demonstrating
      that synaptobrevin 1 is responsible for the remaining release activity. These
      data support the hypothesis that both t- and v-SNAREs are absolutely required for
      vesicle priming and evoked release and that differential expression of SNARE
      paralogs can contribute to differential synaptic coding in the brain. 

PMID- 24944212
TI  - Exploring the specific time course of interhemispheric inhibition between the
      human primary sensory cortices.
AB  - The neurophysiological mechanism of interhemispheric inhibition (IHI) between the
      human primary sensory cortices (S1s) is poorly understood. Here we used a paired
      median nerve somatosensory evoked potential protocol to observe S1-S1 IHI from
      the dominant to the nondominant hemisphere with electroencephalography. In 10
      healthy, right-handed individuals, we compared mean peak-to-peak amplitudes of
      five somatosensory evoked potential components (P14/N20, N20/P25, P25/N30,
      N30/P40, and P40/N60) recorded over the right S1 after synchronous versus
      asynchronous stimulation of the right and left median nerves. Asynchronous
      conditioning + test stimuli (CS+TS) were delivered at interstimulus intervals of
      15, 20, 25, 30, and 35 ms. We found that, in relation to synchronous stimulation,
      when a CS to the left S1 preceded a TS to the right S1 at the short intervals (15
      and 20 ms) the amplitude of the cortical N20/P25 complex was significantly
      depressed, whereas at the longer intervals (25, 30, and 35 ms) significant
      inhibition was observed for the thalamocortical P14/N20 as well as the cortical
      N20/P25 components. We conclude that the magnitude of S1 IHI appears to depend on
      the temporal asynchrony of bilateral inputs and the specific timing is likely
      reflective of a direct transcallosal mechanism. Employing a method that enables
      direct S1 IHI to be reliably quantified may provide a novel tool to assess
      potential IHI imbalances in individuals with neurological damage, such as stroke.

PMID- 24944213
TI  - The IGF-derived tripeptide Gly-Pro-Glu is a weak NMDA receptor agonist.
AB  - Glutamate acts as the universal agonist at ionotropic glutamate receptors in part
      because of its high degree of conformational flexibility. Other amino acids and
      small peptides, however, can activate N-methyl-d-aspartate (NMDA) receptors,
      albeit usually with lower affinity and efficacy. Here, we examined the action of
      glycine-proline-glutamate (GPE), a naturally occurring tripeptide formed in the
      brain following cleavage of IGF-I. GPE is thought to have biological activity in
      the brain, but its mechanism of action remains unclear. With its flanking
      glutamate and glycine residues, GPE could bind to either the agonist or coagonist
      sites on NMDA receptors, however, this has not been directly tested. Using whole
      cell patch-clamp recordings in combination with rapid solution exchange, we
      examined both steady-state currents induced by GPE as well as the effects of GPE
      on synaptically evoked currents. High concentrations of GPE evoked inward
      currents, which were blocked either by NMDA receptor competitive antagonists or
      the voltage-dependent channel blocker Mg(2+). GPE also produced a slight
      attenuation in the NMDA- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA)-mediated excitatory postsynaptic currents without altering the paired
      pulse ratio. Our results suggest that GPE can activate NMDA receptors but at
      concentrations well above the expected concentration of GPE in the brain.
      Therefore, it is unlikely that endogenous GPE interacts with glutamate receptors
      under normal conditions. 

PMID- 24944214
TI  - Reduced chemical and electrical connections of fast-spiking interneurons in
      experimental cortical dysplasia.
AB  - Aberrant neural connections are regarded as a principal factor contributing to
      epileptogenesis. This study examined chemical and electrical connections between
      fast-spiking (FS), parvalbumin (PV)-immunoreactive (FS-PV) interneurons and
      regular-spiking (RS) neurons (pyramidal neurons or spiny stellate neurons) in a
      rat model of prenatal irradiation-induced cortical dysplasia. Presynaptic action
      potentials were evoked by current injection and the elicited unitary inhibitory
      or excitatory postsynaptic potentials (uIPSPs or uEPSPs) were recorded in the
      postsynaptic cell. In dysplastic cortex, connection rates between presynaptic FS
      PV interneurons and postsynaptic RS neurons and FS-PV interneurons, and uIPSP
      amplitudes were significantly smaller than controls, but both failure rates and
      coefficient of variation of uIPSP amplitudes were larger than controls. In
      contrast, connection rates from RS neurons to FS-PV interneurons and uEPSPs
      amplitude were similar in the two groups. Assessment of the paired pulse ratio
      showed a significant decrease in synaptic release probability at FS-PV
      interneuronal terminals, and the density of terminal boutons on axons of biocytin
      filled FS-PV interneurons was also decreased, suggesting presynaptic dysfunction
      in chemical synapses formed by FS-PV interneurons. Electrical connections were
      observed between FS-PV interneurons, and the connection rates and coupling
      coefficients were smaller in dysplastic cortex than controls. In dysplastic
      cortex, we found a reduced synaptic efficiency for uIPSPs originating from FS-PV
      interneurons regardless of the type of target cell, and impaired electrical
      connections between FS-PV interneurons. This expands our understanding of the
      fundamental impairment of inhibition in this model and may have relevance for
      certain types of human cortical dysplasia. 

PMID- 24944215
TI  - The cost of moving optimally: kinematic path selection.
AB  - It is currently unclear whether the brain plans movement kinematics explicitly or
      whether movement paths arise implicitly through optimization of a cost function
      that takes into account control and/or dynamic variables. Several cost functions
      are proposed in the literature that are very different in nature (e.g., control
      effort, torque change, and jerk), yet each can predict common movement
      characteristics. We set out to disentangle predictions of the different variables
      using a combination of modeling and empirical studies. Subjects performed goal
      directed arm movements in a force field (FF) in combination with visual
      perturbations of seen hand position. This FF was designed to have distinct
      optimal movements for muscle-input and dynamic costs while leaving kinematic cost
      unchanged. Visual perturbations in turn changed the kinematic cost but left the
      dynamic and muscle-input costs unchanged. An optimally controlled,
      physiologically realistic arm model was used to predict movements under the
      various cost variables. Experimental results were not consistent with a cost
      function containing any of the control and dynamic costs investigated. Movement
      patterns of all experimental conditions were adequately predicted by a kinematic
      cost function comprising both visually and somatosensory perceived jerk. The
      present study provides clear behavioral evidence that the brain solves kinematic
      and mechanical redundancy in separate steps: in a first step, movement kinematics
      are planned; and in a second, separate step, muscle activation patterns are
      generated.

PMID- 24944216
TI  - Operant conditioning of the soleus H-reflex does not induce long-term changes in
      the gastrocnemius H-reflexes and does not disturb normal locomotion in humans.
AB  - In normal animals, operant conditioning of the spinal stretch reflex or the H
      reflex has lesser effects on synergist muscle reflexes. In rats and people with
      incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can
      improve locomotion. We studied in normal humans the impact of soleus H-reflex
      down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on
      locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During
      conditioning trials, the subject was encouraged to decrease soleus H-reflex size
      with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were
      measured. Locomotion was assessed before and after conditioning. In successfully
      conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of
      within-session (task dependent) adaptation (13.2%) and across-session (long term)
      change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent
      adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long
      term change. No consistent changes were detected across subjects in locomotor H
      reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans,
      soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H
      reflexes and does not change locomotion. In these subjects, task-dependent
      adaptation of the soleus H-reflex is greater than it is in people with SCI,
      whereas long-term change is less. This difference from results in people with SCI
      is consistent with the fact that long-term change is beneficial in people with
      SCI, since it improves locomotion. In contrast, in normal subjects, long-term
      change is not beneficial and may necessitate compensatory plasticity to preserve
      satisfactory locomotion. 

PMID- 24944217
TI  - Voxel-based morphometry and arterial spin labeling fMRI reveal neuropathic and
      neuroplastic features of brain processing of itch in end-stage renal disease.
AB  - Pruritus of end-stage renal disease (ESRD) is a multifactorial symptom of complex
      etiology not yet fully understood. In this study we have investigated the
      cerebral perfusion patterns at rest in ESRD patients on hemodialysis, compared
      with those in healthy volunteers. We have also studied the brain responses evoked
      by experimental itch induction in ESRD, after stimulating the two distinct
      histamine and cowhage itch pathways, and compared them with the responses evoked
      in healthy volunteers. To identify potential structural alterations in ESRD
      patients compared with a group of age-matched healthy volunteers, we calculated
      the density of gray matter for the entire brain using a voxel-based morphometric
      analysis. Our results indicated that gray matter density was significantly
      reduced in ESRD patients in the frontal, parietal, temporal, and occipital
      cortices, as well as in the S1, precuneus, and insula, whereas the brain stem,
      hippocampus, amygdala, midcingulate cortex, and nucleus accumbens displayed an
      increased gray matter density. Functionally, we found a significantly higher
      brain perfusion at baseline associated with ESRD pruritus in the anterior
      cingulate, insula, claustrum, hippocampus, and nucleus accumbens. The brain
      responses evoked by cowhage itch, which are mediated by protease-activated
      receptors (PAR2), displayed significant differences compared with responses in
      healthy individuals and were correlated with perceived itch intensity in a dual,
      complex manner. The inverse correlations in particular suggested that a negative
      feedback mechanism modulated itch intensity, when elicited in a preexistent
      chronic itch background. 

PMID- 24944219
TI  - Azimuth and envelope coding in the inferior colliculus of the unanesthetized
      rabbit: effect of reverberation and distance.
AB  - Recognition and localization of a sound are the major functions of the auditory
      system. In real situations, the listener and different degrees of reverberation
      transform the signal between the source and the ears. The present study was
      designed to provide these transformations and examine their influence on neural
      responses. Using the virtual auditory space (VAS) method to create anechoic and
      moderately and highly reverberant environments, we found the following: 1) In
      reverberation, azimuth tuning was somewhat degraded with distance whereas the
      direction of azimuth tuning remained unchanged. These features remained unchanged
      in the anechoic condition. 2) In reverberation, azimuth tuning and envelope
      synchrony were degraded most for neurons with low best frequencies and least for
      neurons with high best frequencies. 3) More neurons showed envelope synchrony to
      binaural than to monaural stimulation in both anechoic and reverberant
      environments. 4) The percentage of envelope-coding neurons and their synchrony
      decreased in reverberation with distance, whereas it remained constant in the
      anechoic condition. 5) At far distances, for both binaural and monaural
      stimulation, the neural gain in reverberation could be as high as 30 dB and as
      much as 10 dB higher than those in the anechoic condition. 6) The majority of
      neurons were able to code both envelope and azimuth in all of the environments.
      This study provides a foundation for understanding the neural coding of azimuth
      and envelope synchrony at different distances in reverberant and anechoic
      environments. This is necessary to understand how the auditory system processes
      "where" and "what" information in real environments. 

PMID- 24944218
TI  - Connection-type-specific biases make uniform random network models consistent
      with cortical recordings.
AB  - Uniform random sparse network architectures are ubiquitous in computational
      neuroscience, but the implicit hypothesis that they are a good representation of
      real neuronal networks has been met with skepticism. Here we used two
      experimental data sets, a study of triplet connectivity statistics and a data set
      measuring neuronal responses to channelrhodopsin stimuli, to evaluate the
      fidelity of thousands of model networks. Network architectures comprised three
      neuron types (excitatory, fast spiking, and nonfast spiking inhibitory) and were
      created from a set of rules that govern the statistics of the resulting
      connection types. In a high-dimensional parameter scan, we varied the degree
      distributions (i.e., how many cells each neuron connects with) and the synaptic
      weight correlations of synapses from or onto the same neuron. These variations
      converted initially uniform random and homogeneously connected networks, in which
      every neuron sent and received equal numbers of synapses with equal synaptic
      strength distributions, to highly heterogeneous networks in which the number of
      synapses per neuron, as well as average synaptic strength of synapses from or to
      a neuron were variable. By evaluating the impact of each variable on the network
      structure and dynamics, and their similarity to the experimental data, we could
      falsify the uniform random sparse connectivity hypothesis for 7 of 36
      connectivity parameters, but we also confirmed the hypothesis in 8 cases. Twenty
      one parameters had no substantial impact on the results of the test protocols we
      used.

PMID- 24944220
TI  - Investigation of the juxtamembrane region of neuronal-Synaptobrevin in synaptic
      transmission at the Drosophila neuromuscular junction.
AB  - In this study, the juxtamembrane region of the Drosophila SNARE protein neuronal
      Synaptobrevin (n-Syb) was tested for its role in synaptic transmission. A
      transgenic approach was used to express n-Syb mutant genes. The transgenes
      carried engineered point mutations that alter the amino acid sequence of the
      conserved tryptophan residues in the juxtamembrane sequence. Such transgenes were
      expressed in an n-syb hypomorphic background, which produces little endogenous
      protein. On their own, hypomorphic flies displayed severe motor inhibition,
      limited life span, reduced evoked junctional potentials (EJPs), decreased
      synchronicity in EJP time to peak, and potentiation of EJPs with 10-Hz
      stimulation. All of these deficits were restored to wild-type levels with the
      expression of wild-type transgenic n-syb, regulated by the endogenous promoter (n
      syb(WT)). We created transgenic mutants with one additional tryptophan (n
      syb(WW)) or one less tryptophan (n-syb(AA)) than the wild-type sequence. While n
      syb(WW) resembled n-syb(WT) in all variables listed, n-syb(AA) exhibited
      decreased EJP amplitude, synchronicity, and quantal content. To determine whether
      the n-syb juxtamembrane region is important for transduction of force arising
      from SNARE complex assembly during membrane fusion, we introduced short 6-amino
      acid (n-syb(L6)) or long 24-amino acid (n-syb(L24)) flexible linkers into the n
      syb transgene. We observed a reduced EJP amplitude in n-syb(L6) but not n
      syb(L24), while both linker mutants showed a decreased quantal content and an
      effect on the readily releasable and recycling vesicle pools. In conclusion,
      mutation of the juxtamembrane region of n-syb deleteriously affected synaptic
      transmission at the Drosophila neuromuscular junction. 

PMID- 24944222
TI  - Why wet feels wet? A neurophysiological model of human cutaneous wetness
      sensitivity.
AB  - Although the ability to sense skin wetness and humidity is critical for
      behavioral and autonomic adaptations, humans are not provided with specific skin
      receptors for sensing wetness. It has been proposed that we "learn" to perceive
      the wetness experienced when the skin is in contact with a wet surface or when
      sweat is produced through a multisensory integration of thermal and tactile
      inputs generated by the interaction between skin and moisture. However, the
      individual roles of thermal and tactile cues and how these are integrated
      peripherally and centrally by our nervous system is still poorly understood. Here
      we tested the hypothesis that the central integration of coldness and
      mechanosensation, as subserved by peripheral A-nerve afferents, might be the
      primary neural process underpinning human wetness sensitivity. During a
      quantitative sensory test, we found that individuals perceived warm-wet and
      neutral-wet stimuli as significantly less wet than cold-wet stimuli, although
      these were characterized by the same moisture content. Also, when cutaneous cold
      and tactile sensitivity was diminished by a selective reduction in the activity
      of A-nerve afferents, wetness perception was significantly reduced. Based on a
      concept of perceptual learning and Bayesian perceptual inference, we developed
      the first neurophysiological model of cutaneous wetness sensitivity centered on
      the multisensory integration of cold-sensitive and mechanosensitive skin
      afferents. Our results provide evidence for the existence of a specific
      information processing model that underpins the neural representation of a
      typical wet stimulus. These findings contribute to explaining how humans sense
      warm, neutral, and cold skin wetness. 

PMID- 24944221
TI  - Organization of pontine reticulospinal inputs to motoneurons controlling axial
      and limb muscles in the neonatal mouse.
AB  - Using optical recording of synaptically mediated calcium transients and selective
      spinal lesions, we investigated the pattern of activation of spinal motoneurons
      (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord
      preparations from the neonatal mouse. Stimulation sites throughout the region
      where the pontine reticulospinal neurons reside reliably activated MNs at
      cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi- and
      contralateral to the stimulation site, similar in medial and lateral motor
      columns that contain trunk and limb MNs, respectively, and similar in the L2 and
      L5 segments that predominantly contain flexor and extensor MNs, respectively. In
      nonlesioned preparations, responses in both ipsi- and contralateral MNs followed
      individual stimuli in stimulus trains nearly one-to-one (with few failures).
      After unilateral hemisection at C1 on the same side as the stimulation, responses
      had substantially smaller magnitudes and longer latencies and no longer followed
      individual stimuli. After unilateral hemisection at C1 on the side opposite to
      the stimulation, the responses were also smaller, but their latencies were not
      affected. Thus we distinguish two pontine reticulospinal pathways to spinal MNs,
      one uncrossed and the other crossed, of which the uncrossed pathway transmits
      more faithfully and appears to be more direct. 

PMID- 24944223
TI  - Infrared detection without specialized infrared receptors in the bloodsucking bug
      Rhodnius prolixus.
AB  - Bloodsucking bugs use infrared radiation (IR) for locating warm-blooded hosts and
      are able to differentiate between infrared and temperature (T) stimuli. This
      paper is concerned with the neuronal coding of IR in the bug Rhodnius prolixus.
      Data obtained are from the warm cells in the peg-in-pit sensilla (PSw cells) and
      in the tapered hairs (THw cells). Both warm cells responded to oscillating
      changes in air T and IR with oscillations in their discharge rates. The PSw cells
      produced stronger responses to T oscillations than the THw cells. Oscillations in
      IR did the reverse: they stimulated the latter more strongly than the former. The
      reversal in the relative excitability of the two warm cell types provides a
      criterion to distinguish between changes in T and IR. The existence of strongly
      responsive warm cells for one or the other stimulus in a paired comparison is the
      distinguishing feature of a "combinatory coding" mechanism. This mechanism
      enables the information provided by the difference or the ratio between the
      response magnitudes of both cell types to be utilized by the nervous system in
      the neural code for T and IR. These two coding parameters remained constant,
      although response strength changed when the oscillation period was altered. To
      discriminate between changes in T and IR, two things are important: which sensory
      cell responded to either stimulus and how strong was the response. The label warm
      or infrared cell may indicate its classification, but the functions are only
      given in the context of activity produced in parallel sensory cells. 

PMID- 24944224
TI  - Dendritic spine heterogeneity and calcium dynamics in basolateral amygdala
      principal neurons.
AB  - Glutamatergic synapses on pyramidal neurons are formed on dendritic spines where
      glutamate activates ionotropic receptors, and calcium influx via N-methyl-d
      aspartate receptors leads to a localized rise in spine calcium that is critical
      for the induction of synaptic plasticity. In the basolateral amygdala, activation
      of metabotropic receptors is also required for synaptic plasticity and amygdala
      dependent learning. Here, using acute brain slices from rats, we show that, in
      basolateral amygdala principal neurons, high-frequency synaptic stimulation
      activates metabotropic glutamate receptors and raises spine calcium by releasing
      calcium from inositol trisphosphate-sensitive calcium stores. This spine calcium
      release is unevenly distributed, being present in proximal spines, but largely
      absent in more distal spines. Activation of metabotropic receptors also generated
      calcium waves that differentially invaded spines as they propagated toward the
      soma. Dendritic wave invasion was dependent on diffusional coupling between the
      spine and parent dendrite which was determined by spine neck length, with waves
      preferentially invading spines with short necks. Spine calcium is a critical
      trigger for the induction of synaptic plasticity, and our findings suggest that
      calcium release from inositol trisphosphate-sensitive calcium stores may modulate
      homosynaptic plasticity through store-release in the spine head, and
      heterosynaptic plasticity of unstimulated inputs via dendritic calcium wave
      invasion of the spine head. 

PMID- 24944225
TI  - Post-myocardial infarction submitral aneurysm.

PMID- 24944226
TI  - Straying from the path in neuro-oncology.

PMID- 24944227
TI  - Time to begin a new chapter and expand rotavirus immunization.
AB  - Rotavirus immunization has been limited to young infants owing to intussusception
      events noted with a prior rotavirus vaccine, RotaShield. Dramatic declines
      occurred in rotavirus-related disease beginning in 2008 after implementation of
      rotavirus vaccination in young infants. These declines occurred in vaccinated
      children and unvaccinated children and adults (through indirect protection).
      Despite these declines, reasons for concern exist about the durability of these
      declines. These reasons include an incomplete immune response that is not
      lifelong and rotavirus immunization completion rates that have plateaued at <70%
      of eligible children. Current rotavirus infant vaccination strategies and
      indirect protection of unvaccinated children will result in a large population of
      immunologically susceptible persons who will be at risk of rotavirus disease.
      Expansion of US rotavirus vaccination outside the current Advisory Committee on
      Immunization Practices recommended immunization age limits would provide
      important benefits that outweigh risk related to intussusception. 

PMID- 24944229
TI  - Shifting gears to control drug-resistant tuberculosis.

PMID- 24944228
TI  - Reaching the london declaration on neglected tropical diseases goals for
      onchocerciasis: an economic evaluation of increasing the frequency of ivermectin
      treatment in Africa.
AB  - BACKGROUND: Recently, there has been a shift in onchocerciasis control policy,
      changing from prevention of morbidity toward elimination of infection. Switching
      from annual to biannual ivermectin distribution may accelerate progress toward
      the elimination goals. However, the settings where this strategy would be cost
      effective in Africa have not been described. METHODS: An onchocerciasis
      transmission framework (EpiOncho) was coupled to a disease model in order to
      explore the impact on disability-adjusted life years averted, program cost, and
      program duration of biannual ivermectin treatment in different epidemiological
      and programmatic scenarios in African savannah. RESULTS: While biannual treatment
      yields only small additional health gains, its benefit is pronounced in the
      context of the elimination goals, shortening the time frames for and increasing
      the feasibility of reaching the proposed operational thresholds for stopping
      treatment. In settings with high precontrol endemicity (and/or poor coverage and
      compliance), it may not be possible to reach such thresholds even within 50 years
      of annual ivermectin, requiring adoption of biannual treatment. Our projections
      highlight the crucial role played by coverage and compliance in achieving the
      elimination goals. CONCLUSIONS: Biannual ivermectin treatment improves the
      chances of reaching the 2020/2025 elimination goals, potentially generating
      programmatic cost savings in settings with high precontrol endemicity. However,
      its benefit and cost are highly sensitive to levels of systematic noncompliance
      and, in many settings, it will lead to an increase in costs. Furthermore, it may
      not always be feasible to implement biannual treatment, particularly in hard-to
      reach populations. This highlights the continued need for a macrofilaricide.

PMID- 24944230
TI  - Seasonal amplitude of hemorrhagic fever with renal syndrome in China: a call for
      attention to neglected regions.

PMID- 24944231
TI  - Outbreak of Francisella novicida bacteremia among inmates at a louisiana
      correctional facility.
AB  - BACKGROUND: Francisella novicida is a rare cause of human illness despite its
      close genetic relationship to Francisella tularensis, the agent of tularemia.
      During April-July 2011, 3 inmates at a Louisiana correctional facility developed
      F. novicida bacteremia; 1 inmate died acutely. METHODS: We interviewed surviving
      inmates; reviewed laboratory, medical, and housing records; and conducted an
      environmental investigation. Clinical and environmental samples were tested by
      culture, real-time polymerase chain reaction (PCR), and multigene sequencing.
      Isolates were typed by pulsed-field gel electrophoresis (PFGE). RESULTS: Clinical
      isolates were identified as F. novicida based on sequence analyses of the 16S
      ribosomal RNA, pgm, and pdpD genes. PmeI PFGE patterns for the clinical isolates
      were indistinguishable. Source patients were aged 40-56 years, male, and African
      American, and all were immunocompromised. Two patients presented with signs of
      bacterial peritonitis; the third had pyomyositis of the thigh. The 3 inmates had
      no contact with one another; their only shared exposures were consumption of
      municipal water and of ice that was mass-produced at the prison in an unenclosed
      building. Swabs from one set of ice machines and associated ice scoops yielded
      evidence of F. novicida by PCR and sequencing. All other environmental specimens
      tested negative. CONCLUSIONS: To our knowledge, this is the first reported common
      source outbreak of F. novicida infections in humans. Epidemiological and
      laboratory evidence implicate contaminated ice as the likely vehicle of
      transmission; liver disease may be a predisposing factor. Clinicians,
      laboratorians, and public health officials should be aware of the potential for
      misidentification of F. novicida as F. tularensis.

PMID- 24944233
TI  - HIV-1 transmission networks among men who have sex with men in Asia.

PMID- 24944234
TI  - Two concurrent enteric disease outbreaks among men who have sex with men,
      minneapolis-st paul area.
AB  - Between 1 November 2013 and 31 March 2014, concurrent shigellosis and
      cryptosporidiosis outbreaks occurred among men who have sex with men in the
      Minneapolis-St. Paul area, 75% of whom were HIV-infected. Current HIV/AIDS
      strategy emphasizing treatment as prevention may effectively decrease HIV
      transmission, but raises concerns about other diseases if safer sex messages are
      de-emphasized. 

PMID- 24944232
TI  - ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir
      in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects.
AB  - BACKGROUND: Dolutegravir (DTG), a once-daily, human immunodeficiency virus type 1
      (HIV-1) integrase inhibitor, was evaluated for distribution and antiviral
      activity in cerebrospinal fluid (CSF). METHODS: ING116070 is an ongoing, single
      arm, open-label, multicenter study in antiretroviral therapy-naive, HIV-1
      infected adults. Subjects received DTG (50 mg) plus abacavir/lamivudine (600/300
      mg) once daily. The CSF and plasma (total and unbound) DTG concentrations were
      measured at weeks 2 and 16. The HIV-1 RNA levels were measured in CSF at baseline
      and weeks 2 and 16 and in plasma at baseline and weeks 2, 4, 8, 12, and 16.
      RESULTS: Thirteen white men enrolled in the study; 2 withdrew prematurely, 1
      because of a non-drug-related serious adverse event (pharyngitis) and 1 because
      of lack of treatment efficacy. The median DTG concentrations in CSF were 18 ng/mL
      (range, 4-23 ng/mL) at week 2 and 13 ng/mL (4-18 ng/mL) at week 16. Ratios of DTG
      CSF to total plasma concentration were similar to the unbound fraction of DTG in
      plasma. Median changes from baseline in CSF (n = 11) and plasma (n = 12) HIV-1
      RNA were -3.42 and -3.04 log10 copies/mL, respectively. Nine of 11 subjects (82%)
      had plasma and CSF HIV-1 RNA levels <50 copies/mL and 10 of 11 (91%) had CSF HIV
      1 RNA levels <2 copies/mL at week 16. CONCLUSIONS: The DTG concentrations in CSF
      were similar to unbound plasma concentrations and exceeded the in vitro 50%
      inhibitory concentration for wild-type HIV (0.2 ng/mL), suggesting that DTG
      achieves therapeutic concentrations in the central nervous system. The HIV-1 RNA
      reductions were similar in CSF and plasma. Clinical Trials Registration.
      NCT01499199.

PMID- 24944235
TI  - Hepatic decompensation in patients with HIV/Hepatitis B Virus (HBV)/Hepatitis C
      Virus (HCV) triple infection versus HIV/HCV coinfection and the effect of anti
      HBV nucleos(t)ide therapy.
AB  - The incidence rate of hepatic decompensation was higher in patients with human
      immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV)
      triple infection than in those with HIV/HCV coinfection (24.1 vs 10.8 events per
      1000 person-years; hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.12
      3.18). Compared with HIV/HCV-infected patients, the rate of decompensation was
      increased among HIV/HBV/HCV-infected patients receiving no anti-HBV therapy (HR,
      2.48; 95% CI, 1.37-4.49) but not among those who did receive such therapy (HR,
      1.09; 95% CI, .40-2.97). 

PMID- 24944236
TI  - Overview of the in vitro stability of commonly measured vitamins and carotenoids
      in whole blood.
AB  - BACKGROUND: The pre-analytical stabilities of vitamins A, E, K, B1, B2, B6, B12,
      C, carotenoids and folates in whole blood were studied. The aim of this work was
      to provide clear and workable pre-analytical procedures specifying optimal delay
      before freezing for laboratories which perform themselves such analyses or which
      receive and transfer such specimens to referral laboratories. METHODS: The
      stability of vitamins was studied in whole blood at room temperature after light
      exposure up to 24 h (vitamin C), 48 h (vitamins A, E, B1, B2, B6 and carotenoids)
      and 72 h (vitamins K, B12, red blood cell (RBC) and serum folates). Vitamin C
      stability after baseline acidification was analysed up to 48 h. Changes observed
      were compared to a clinical cut-off defined as total change limit based on a
      combination of analytical performance and within-subject variation. RESULTS:
      Clinically and statistically significant changes occurred only in vitamins C (
      22.5%), B6 (+9.9%) and serum folates (-16.8%) concentrations after 6, 24 and 48
      h, respectively. Vitamins A, E, K, B1, B2, B12, RBC folates and carotenoids
      showed good stability up to 48 or 72 h. Vitamin C in acidified serum conserved at
      room temperature appeared unstable. The optimal condition for acidified vitamin C
      conservation was at less than -20C. CONCLUSION: The majority of vitamins remain
      stable for up to 48 h. Vitamin C quantification requires serum acidification
      followed by freezing as soon as possible. Freezing, respectively, within 12 h and
      24 h for determination of plasma vitamin B6 and serum folates concentrations is
      recommended.

PMID- 24944237
TI  - How color, regularity, and good Gestalt determine backward masking.
AB  - The strength of visual backward masking depends on the stimulus onset asynchrony
      (SOA) between target and mask. Recently, it was shown that the conjoint spatial
      layout of target and mask is as crucial as SOA. Particularly, masking strength
      depends on whether target and mask group with each other. The same is true in
      crowding where the global spatial layout of the flankers and target-flanker
      grouping determine crowding strength. Here, we presented a vernier target
      followed by different flanker configurations at varying SOAs. Similar to
      crowding, masking of a red vernier target was strongly reduced for arrays of 10
      green compared with 10 red flanking lines. Unlike crowding, single green lines
      flanking the red vernier showed strong masking. Irregularly arranged flanking
      lines yielded stronger masking than did regularly arranged lines, again similar
      to crowding. While cuboid flankers reduced crowding compared with single lines,
      this was not the case in masking. We propose that, first, masking is reduced when
      the flankers are part of a larger spatial structure. Second, spatial factors
      counteract color differences between the target and the flankers. Third, complex
      Gestalts, such as cuboids, seem to need longer processing times to show
      ungrouping effects as observed in crowding. Strong parallels between masking and
      crowding suggest similar underlying mechanism; however, temporal factors in
      masking additionally modulate performance, acting as an additional grouping cue.

PMID- 24944238
TI  - Quantifying the effect of intertrial dependence on perceptual decisions.
AB  - In the perceptual sciences, experimenters study the causal mechanisms of
      perceptual systems by probing observers with carefully constructed stimuli. It
      has long been known, however, that perceptual decisions are not only determined
      by the stimulus, but also by internal factors. Internal factors could lead to a
      statistical influence of previous stimuli and responses on the current trial,
      resulting in serial dependencies, which complicate the causal inference between
      stimulus and response. However, the majority of studies do not take serial
      dependencies into account, and it has been unclear how strongly they influence
      perceptual decisions. We hypothesize that one reason for this neglect is that
      there has been no reliable tool to quantify them and to correct for their
      effects. Here we develop a statistical method to detect, estimate, and correct
      for serial dependencies in behavioral data. We show that even trained
      psychophysical observers suffer from strong history dependence. A substantial
      fraction of the decision variance on difficult stimuli was independent of the
      stimulus but dependent on experimental history.We discuss the strong dependence
      of perceptual decisions on internal factors and its implications for correct data
      interpretation.

PMID- 24944240
TI  - Antiretroviral-Related Alopecia in HIV-Infected Patients.
AB  - : Objective: To review the literature evaluating antiretroviral-related alopecia
      and to provide guidance on the differential diagnosis and management of this
      condition. DATA SOURCES: A literature search was performed using PubMed, MEDLINE,
      Embase, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing
      and Allied Health (CINAHL), and the Cochrane database (through May 2014).
      Relevant conference abstracts and product monographs were reviewed. Search terms
      included antiretroviral, individual antiretroviral classes and names, highly
      active antiretroviral therapy, HIV, AIDS, alopecia, hair, hair loss and drug.
      STUDY SELECTION AND DATA EXTRACTION: English-language studies and case reports
      were included. A total of 16 articles and 1 conference abstract were retrieved,
      with a total of 46 patients with hair loss. DATA SYNTHESIS: The protease
      inhibitor class, in particular indinavir, was most commonly reported to cause
      hair loss, followed by the NRTI, lamivudine. The majority of cases presented with
      alopecia of the scalp alone, with a median time of onset of 2.5 months.
      Management involved discontinuing the drug in most cases, with at least partial
      reversal in half the cases. CONCLUSIONS: In antiretroviral-induced alopecia,
      discontinuation of the suspected agent is the optimal management, and hair
      regrowth should occur within 1 to 3 months. Management may also include replacing
      the offending medication with an antiretroviral less likely to cause hair loss.
      It is essential to rule out other causes of alopecia with a complete patient
      history, including characterization of the hair loss and assessment of the
      patient's medical history, medication use, and family history of alopecia.

PMID- 24944239
TI  - Safety of therapeutic hypothermia combined with primary percutaneous coronary
      intervention after out-of-hospital cardiac arrest.
AB  - BACKGROUND: The safety of therapeutic hypothermia combined with percutaneous
      coronary intervention (PCI) after out-of-hospital cardiac arrest has been
      challenged after reports of high risk of stent thrombosis. METHODS: We searched
      the Western Denmark Heart Registry to identify patients with an acute coronary
      angiography due to out-of-hospital cardiac arrest performed at our institution
      between September 2010 and September 2013. We identified 68 unconscious patients,
      who were resuscitated after out-of-hospital cardiac arrest and underwent acute
      PCI with stent implantation and immediate therapeutic hypothermia, and followed
      these for 30 days. Target temperature of 32-34 degrees C was achieved by either
      an invasive or a non-invasive cooling system. RESULTS: All patients had elevated
      myocardial biomarkers and 37 patients had ST-segment elevation myocardial
      infarction. Bare metal stents were implanted in 14 and drug-eluting stents in 54
      patients. All patients received antithrombotic treatment with a standard loading
      dose of 300 mg acetylsalicylic acid and 10,000 units heparin intravenously prior
      PCI. Clopidogrel or ticagrelor was administered orally through a gastric tube
      immediately after PCI. During the procedure abciximab or bivalirudin was
      administered in 44 patients. Electrocardiographic and clinical signs of stent
      thrombosis were found in one patient. CONCLUSIONS: We observed one stent
      thrombosis in this cohort of 68 consecutive patients with out-of-hospital cardiac
      arrest who were treated with PCI and therapeutic hypothermia. This suggests that
      PCI with stent implantation can be performed with acceptable safety in these
      patients.

PMID- 24944241
TI  - Estrogen status and the renin angiotensin aldosterone system.
AB  - The renin-angiotensin-aldosterone system (RAAS) is integrally involved in
      multiple cardiovascular physiological processes including arterial blood pressure
      (BP) regulation. Over activity of the RAAS has been implicated in the
      pathogenesis of a number of cardiovascular disease entities, including
      hypertension. Several lines of evidence suggest estrogen favorably modulates the
      RAAS. Conversely, estrogen deficiency due to menopause may contribute to over
      activity of the RAAS. Of importance, estrogen deficiency in women is not
      exclusive to the postmenopausal period. Functional hypothalamic amenorrhea is a
      reversible cause of premenopausal hypoestrogenemia. In contrast to postmenopausal
      women (PMW), premenopausal women with exercise-associated functional hypothalamic
      amenorrhea demonstrate decreased, not increased, resting BP compared with their
      estrogen-replete eumenorrheic counterpart. In this review we briefly examine the
      effects of estrogen status on the RAAS and present the hypothesis that the RAAS
      is altered in physically active women with functional hypothalamic amenorrhea. 

PMID- 24944243
TI  - Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling
      reduces appetitive and motivational aspects of feeding.
AB  - Central glucagon-like peptide-1 receptor (GLP-1R) signaling reduces food intake
      by affecting a variety of neural processes, including those mediating satiation,
      motivation, and reward. While the literature suggests that separable neurons and
      circuits control these processes, this notion has not been adequately
      investigated. The intake inhibitory effects of GLP-1R signaling in the hindbrain
      medial nucleus tractus solitarius (mNTS) have been attributed to interactions
      with vagally transmitted gastrointestinal satiation signals that are also
      processed by these neurons. Here, behavioral and pharmacological techniques are
      used to test the novel hypothesis that the reduction of food intake following
      mNTS GLP-1R stimulation also results from effects on food-motivated appetitive
      behaviors. Results show that mNTS GLP-1R activation by microinjection of exendin
      4, a long-acting GLP-1R agonist, reduced 1) intake of a palatable high-fat diet,
      2) operant responding for sucrose under a progressive ratio schedule of
      reinforcement and 3) the expression of a conditioned place preference for a
      palatable food. Together, these data demonstrate that the intake inhibitory
      effects of mNTS GLP-1R signaling extend beyond satiation and include effects on
      food reward and motivation that are typically ascribed to midbrain and forebrain
      neurons. 

PMID- 24944242
TI  - Characterization of the effects of the vasopressin V2 receptor on sweating, fluid
      balance, and performance during exercise.
AB  - A regulatory effect of arginine vasopressin (AVP) on sweat water conservation has
      been hypothesized but not definitively evaluated. AVP-mediated insertion of sweat
      and salivary gland aquaporin-5 (AQP5) water channels through activation of the
      vasopressin type 2 receptor (V2R) remains an attractive, yet unexplored,
      mechanism that could result in a more concentrated sweat with resultant decreased
      water loss. Ten runners participated in a double-blind randomized control
      treadmill trial under three separate pharmacological conditions: a placebo, V2R
      agonist (0.2 mg desmopressin), or V2R antagonist (30 mg tolvaptan). After a
      familiarization trial, runners ran for 60 min at 60% of peak speed followed by a
      performance trial to volitional exhaustion. Outcome variables were collected at
      three exercise time points: baseline, after the steady-state run, and after the
      performance run. Body weight losses were <2% across all three trials. Significant
      pharmacological condition effects were noted for urine osmolality [F = 84.98; P <
      0.0001] and urine sodium concentration ([Na(+)]) [F = 38.9; P < 0.0001], which
      verified both pharmacological activation and inhibition of the V2R at the kidney
      collecting duct. Plasma osmolality and [Na(+)] demonstrated significant exercise
      (F = 26.0 and F = 11.1; P < 0.0001) and condition (F = 5.1 and F = 3.8; P < 0.05)
      effects (osmolality and [Na(+)], respectively). No significant exercise or
      condition effects were noted for either sweat or salivary [Na(+)]. Significant
      exercise effects were noted for plasma [AVP] (F = 22.3; P < 0.0001), peak core
      temperature (F = 103.3; P < 0.0001), percent body weight change (F = 6.3; P =
      0.02), plasma volume change (F = 21.8; P < 0.0001), and thirst rating (F = 78.2;
      P < 0.0001). Performance time was not altered between conditions (P = 0.80). In
      summary, AVP acting at V2R does not appear to regulate water losses from body
      fluids other than renal excretion during exercise. 

PMID- 24944244
TI  - The ins and outs of angiotensin processing within the kidney.
AB  - The kidney is a key target organ for bioactive components of the renin
      angiotensin system (RAS); however, various renal cells such as the tubular
      epithelium contain an intrinsic RAS. The renal RAS can be functionally divided
      into ANG II-AT1 receptor and ANG-(1-7)-AT7/Mas receptor arms that functionally
      oppose one another. The current review considers both extracellular and
      intracellular pathways that potentially govern the formation and metabolism of
      angiotensin peptides within the renal proximal tubules. 

PMID- 24944245
TI  - Lack of hormonal stimulation prevents the landlocked Biwa salmon (Oncorhynchus
      masou subspecies) from adapting to seawater.
AB  - Landlocking of salmon relaxes selective pressures on hypoosmoregulatory ability
      (seawater adaptability) and may lead to the abandonment of its physiological
      system. However, little is known about the mechanism and consequence of the
      process. Biwa salmon is a strain/subspecies of Oncorhynchus masou that has been
      landlocked in Lake Biwa for an exceptionally long period (about 500,000 years)
      and has low ability to adapt to seawater. We compared activity of gill Na(+),K(+)
      ATPase (NKA) of Biwa salmon with those of anadromous strains of the same species
      (masu and amago salmon) during downstream migration periods and after exogenous
      hormone treatment. Gill NKA activity in anadromous strains increased during their
      migration periods, while that in Biwa salmon remained low. However, treatments of
      Biwa salmon with growth hormone (GH) and cortisol increased gill NKA activity.
      Cortisol treatment also improved the whole body seawater adaptability of Biwa
      salmon. Receptors for GH and cortisol responded to hormonal treatments, whereas
      their mRNA levels during downstream migration period were essentially unchanged
      in Biwa salmon. Circulating levels of cortisol in masu salmon showed a peak
      during downstream migration period, while no such increase was seen in Biwa
      salmon. The present results indicate that Biwa salmon can improve its seawater
      adaptability by exogenous hormonal treatment, and hormone receptors are capable
      of responding to the signals. However, secretion of the endogenous hormone
      (cortisol) was not activated during the downstream migration period, which
      explains, at least in part, their low ability to adapt to seawater. 

PMID- 24944247
TI  - Phosphate absorption across multiple epithelia in the Pacific hagfish (Eptatretus
      stoutii).
AB  - Inorganic phosphate (Pi) is an essential nutrient for all organisms, but in
      seawater, Pi is a limiting nutrient. This study investigated the primary
      mechanisms of Pi uptake in Pacific hagfish (Eptatretus stoutii) using ex vivo
      physiological and molecular techniques. Hagfish were observed to have the
      capacity to absorb Pi from the environment into at least three epithelial
      surfaces: the intestine, skin, and gill. Pi uptake in all tissues was
      concentration dependent, and saturable Pi transport was observed in the skin and
      gill at <2.0 mmol/l Pi. Gill and intestinal Pi uptake was sodium dependent, but
      Pi uptake into the skin increased under low sodium conditions. Gill Pi transport
      exhibited an apparent affinity constant ~0.23-0.6 mmol/l Pi. A complete sequence
      of a type II sodium phosphate cotransporter (Slc34a) was obtained from the
      hagfish gill. Phylogenetic analysis of the hagfish Slc34a transporter indicates
      that it is earlier diverging than, and/or ancestral to, the other identified
      vertebrate Slc34a transporters (Slc34a1, Slc34a2, and Slc34a3). With the use of
      RT-PCR, the hagfish Slc34a transcript was detected in the intestine, skin, gill,
      and kidney, suggesting that this may be the transporter involved in Pi uptake
      into multiple epithelia in the hagfish. This is the first measurement of Pi
      uptake across the gill or skin of any vertebrate animal and first sodium
      phosphate cotransporter identified in hagfish.

PMID- 24944246
TI  - Differential coupling of KLF10 to Sin3-HDAC and PCAF regulates the inducibility
      of the FOXP3 gene.
AB  - Inducible gene expression, which requires chromatin remodeling on gene promoters,
      underlies the epigenetically inherited differentiation program of most immune
      cells. However, chromatin-mediated mechanisms that underlie these events in T
      regulatory cells remain to be fully characterized. Here, we report that
      inducibility of FOXP3, a key transcription factor for the development of T
      regulatory cells, depends upon Kruppel-like factor 10 (KLF10) interacting with
      two antagonistic histone-modifying systems. We utilized chromatin
      immunoprecipitation, genome-integrated reporter assays, and functional domain
      KLF10 mutant proteins, to characterize reciprocal interactions between this
      transcription factor and either the Sin3-histone deacetylase complex or the
      histone acetyltransferase, p300/CBP-associated factor (PCAF). We characterize a
      Sin3-interacting repressor domain on the NH2 terminus of KLF10, which works to
      limit the activating function of this transcription factor. Indeed, inactivation
      of this Sin3-interacting domain renders KLF10 able to physically associate with
      PCAF as to induce FOXP3 gene transcription. We show that this biochemical data
      derived from studying our genome-integrated reporter cell system are
      recapitulated in primary murine lymphocytes. Collectively, these results advance
      our understanding of how a single transcription factor, namely KLF10, functions
      as a toggle to integrate antagonistic signals regulating FOXP3 and, thus, immune
      activation. 

PMID- 24944249
TI  - Sildenafil improves skeletal muscle oxygenation during exercise in men with
      intermittent claudication.
AB  - Endothelial dysfunction caused by defective nitric oxide (NO) signaling plays a
      pivotal role in the pathogenesis of intermittent claudication (IC). In the
      present study, we evaluated the acute effects of sildenafil, a phosphodiesterase
      type 5 inhibitor that acts by prolonging NO-mediated cGMP signaling in vascular
      smooth muscle, on blood pressure (BP), skeletal muscle oxygenation, and walking
      tolerance in patients with IC. A randomized, double-blind, crossover study was
      conducted in which 12 men with stable IC received two consecutive doses of 50 mg
      of sildenafil or matching placebo and underwent a symptom-limited exercise test
      on the treadmill. Changes in gastrocnemius deoxy-hemoglobin by near-infrared
      spectroscopy estimated peripheral muscle O2 delivery-to-utilization matching.
      Systolic BP was significantly lower during the sildenafil trial relative to
      placebo during supine rest (~15 mmHg), submaximal exercise (~14 mmHg), and
      throughout recovery (~18 mmHg) (P < 0.05). Diastolic BP was also lower after
      sildenafil during upright rest (~6 mmHg) and during recovery from exercise (~7
      mmHg) (P < 0.05). Gastrocnemius deoxygenation was consistently reduced during
      submaximal exercise (~41%) and at peak exercise (~34%) following sildenafil
      compared with placebo (P < 0.05). However, pain-free walking time (placebo: 335
      +/- 42 s vs. sildenafil: 294 +/- 35 s) and maximal walking time (placebo: 701 +/-
      58 s vs. sildenafil: 716 +/- 62 s) did not differ between trials. Acute
      administration of sildenafil lowers BP and improves skeletal muscle oxygenation
      during exercise but does not enhance walking tolerance in patients with IC.
      Whether the beneficial effects of sildenafil on muscle oxygenation can be
      sustained over time and translated into positive clinical outcomes deserve
      further consideration in this patient population. 

PMID- 24944248
TI  - Biphasic changes in fetal heart rate variability in preterm fetal sheep
      developing hypotension after acute on chronic lipopolysaccharide exposure.
AB  - Perinatal exposure to infection is highly associated with adverse outcomes.
      Experimentally, acute, severe exposure to gram-negative bacterial
      lipopolysaccharide (LPS) is associated with increased fetal heart rate
      variability (FHRV). It is unknown whether FHRV is affected by subclinical
      infection with or without acute exacerbations. We therefore tested the hypothesis
      that FHRV would be associated with hypotension after acute on chronic exposure to
      LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a
      continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250
      ng.kg(-1).24 h(-1) for a further 96 h) or the same volume of saline (n = 10).
      Boluses of either 1 MUg LPS or saline were given at 48, 72, and 96 h. Low-dose
      infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus
      was associated with tachycardia and suppression of nuchal electromyographic
      activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in
      mean arterial blood pressure >=5 mmHg). FHRV was transiently increased only at
      the onset of hypotension, in association with increased cytokine induction and
      electroencephalogram suppression. FHRV then fell before the nadir of hypotension,
      with transient suppression of short-term FHRV. After the second LPS bolus, the
      hypotension group showed a biphasic pattern of a transient increase in FHRV
      followed by more prolonged suppression. These findings suggest that infection
      related hypotension in the preterm fetus mediates the transient increase in FHRV
      and that repeated exposure to LPS leads to progressive loss of FHRV. 

PMID- 24944250
TI  - Differential regulation of circadian melatonin rhythm and sleep-wake cycle by
      bright lights and nonphotic time cues in humans.
AB  - Our previous study demonstrated that physical exercise under dim lights (<10 lux)
      accelerated reentrainment of the sleep-wake cycle but not the circadian melatonin
      rhythm to an 8-h phase-advanced sleep schedule, indicating differential effects
      of physical exercise on the human circadian system. The present study examined
      the effects of bright light (>5,000 lux) on exercise-induced acceleration of
      reentrainment because timed bright lights are known to reset the circadian
      pacemaker. Fifteen male subjects spent 12 days in temporal isolation. The sleep
      schedule was advanced from habitual sleep times by 8 h for 4 days, which was
      followed by a free-run session. In the shift session, bright lights were given
      during the waking time. Subjects in the exercise group performed 2-h bicycle
      running twice a day. Subjects in the control kept quiet. As a result, the sleep
      wake cycle was fully entrained by the shift schedule in both groups. Bright light
      may strengthen the resetting potency of the shift schedule. By contrast, the
      circadian melatonin rhythm was phase-advanced by 6.9 h on average in the exercise
      group but only by 2.0 h in the control. Thus physical exercise prevented
      otherwise unavoidable internal desynchronization. Polysomnographical analyses
      revealed that deterioration of sleep quality by shift schedule was protected by
      physical exercise under bright lights. These findings indicate differential
      regulation of sleep-wake cycle and circadian melatonin rhythm by physical
      exercise in humans. The melatonin rhythm is regulated primarily by bright lights,
      whereas the sleep-wake cycle is by nonphotic time cues, such as physical exercise
      and shift schedule. 

PMID- 24944251
TI  - Renin release: role of SNAREs.
AB  - Little is known about the molecular mechanism mediating renin granule exocytosis
      and the identity of proteins involved. We previously showed that soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNAREs), a family of
      proteins required for exocytosis, mediate the stimulated release of renin from
      juxtaglomerular cells. This minireview focuses on the current knowledge of the
      proteins that facilitate renin-granule exocytosis. We discuss the identity of
      potential candidates that mediate the signaling and final steps of exocytosis of
      the renin granule. 

PMID- 24944252
TI  - Sex and basic science. A Title IX position.

PMID- 24944254
TI  - Methanol mass poisoning in Iran: role of case finding in outbreak management.
AB  - BACKGROUND: There are no guidelines addressing the public health aspects of
      methanol poisoning during larger outbreaks. The current study was done to discuss
      the role of active case finding and a national guideline that organizes all
      available resources according to a triage strategy in the successful management
      of a methanol mass poisoning in Rafsanjan, Iran, in May 2013. METHODS: A
      retrospective cross-sectional study was performed reviewing the outbreak
      Emergency Operation Center files. The objectives were to describe the
      characteristics, management and outcome of a methanol outbreak using Active Case
      Finding to trace the victims. RESULTS: A total of 694 patients presented to
      emergency departments in Rafsanjan after public announcement of the outbreak
      between 29th May and 3rd June 2013. The announcement was mainly performed via
      short message service (SMS) and local radio broadcasting. A total of 361 cases
      were observed and managed in Rafsanjan and 333 were transferred to other cities.
      Seventy-five and 100 patients underwent hemodialysis (HD), retrospectively. The
      main indication for HD was refractory metabolic acidosis. Eight patients expired
      due to the intoxication. Except for the deceased cases, no serum methanol level
      was available. CONCLUSION: In developing countries, where diagnostic resources
      are limited, use of active case finding and developing national guidelines can
      help in the management of large outbreaks of methanol poisonings.

PMID- 24944253
TI  - Stimulation of the cardiopulmonary baroreflex enhances ventricular contractility
      in awake dogs: a mathematical analysis study.
AB  - The cardiopulmonary baroreflex responds to an increase in central venous pressure
      (CVP) by decreasing total peripheral resistance and increasing heart rate (HR) in
      dogs. However, the direction of ventricular contractility change is not well
      understood. The aim was to elucidate the cardiopulmonary baroreflex control of
      ventricular contractility during normal physiological conditions via a
      mathematical analysis. Spontaneous beat-to-beat fluctuations in maximal
      ventricular elastance (Emax), which is perhaps the best available index of
      ventricular contractility, CVP, arterial blood pressure (ABP), and HR were
      measured from awake dogs at rest before and after beta-adrenergic receptor
      blockade. An autoregressive exogenous input model was employed to jointly
      identify the three causal transfer functions relating beat-to-beat fluctuations
      in CVP to Emax (CVP -> Emax), which characterizes the cardiopulmonary baroreflex
      control of ventricular contractility, ABP to Emax, which characterizes the
      arterial baroreflex control of ventricular contractility, and HR to Emax, which
      characterizes the force-frequency relation. The CVP -> Emax transfer function
      showed a static gain of 0.037 +/- 0.010 ml(-1) (different from zero; P < 0.05)
      and an overall time constant of 3.2 +/- 1.2 s. Hence, Emax would increase and
      reach steady state in ~16 s in response to a step increase in CVP, without any
      change to ABP or HR, due to the cardiopulmonary baroreflex. Following beta
      adrenergic receptor blockade, the CVP -> Emax transfer function showed a static
      gain of 0.0007 +/- 0.0113 ml(-1) (different from control; P < 0.10). Hence, Emax
      would change little in steady state in response to a step increase in CVP.
      Stimulation of the cardiopulmonary baroreflex increases ventricular contractility
      through beta-adrenergic receptor system mediation. 

PMID- 24944255
TI  - Lessons from the dust: are some members more equal than others?

PMID- 24944256
TI  - Rejected applications: an early American Academy of Neurology struggles to define
      its membership.
AB  - OBJECTIVE: To review membership application materials (especially rejected
      applications) to the American Academy of Neurology (AAN) during its formative
      years (1947-1953). METHODS: Detailed study of materials in the AAN Historical
      Collection. RESULTS: The author identified 73 rejected applications. Rejected
      applicants (71 male, 2 female) lived in 25 states. The largest number was for the
      Associate membership category (49). These were individuals "in related fields who
      have made and are making contributions to the field of neurology." By contrast,
      few applicants to Active membership or Fellowship status were rejected. The
      largest numbers of rejectees were neuropsychiatrists (19), neurosurgeons (16),
      and psychiatrists (14). CONCLUSION: The AAN, established in the late 1940s, was a
      small and politically vulnerable organization. A defining feature of the
      fledgling society was its inclusiveness; its membership was less restrictive than
      that of the older American Neurological Association. At the same time, the
      society needed to preserve its core as a neurologic society rather than one of
      psychiatry or neurosurgery. Hence, the balance between inclusiveness and
      exclusive identity was a difficult one to maintain. The Associate membership
      category, more than any other, was at the heart of this issue of self-definition.
      Associate members were largely practitioners of psychiatry or neurosurgery. Their
      membership was a source of consternation and was to be carefully been held in
      check during these critical formative years.

PMID- 24944257
TI  - Shared medical appointments improve QOL in neuromuscular patients: a randomized
      controlled trial.
AB  - OBJECTIVE: To systematically study the effects of shared medical appointments
      (SMAs) compared with individual appointments for patients with a chronic
      neuromuscular disorder and their partners. METHODS: In this randomized controlled
      trial with a follow-up of 6 months, we included patients with a chronic
      neuromuscular disorder and their partners. Participants were randomly allocated
      to an SMA or an individual outpatient appointment. The primary outcome measure
      was patients' health-related quality of life (QOL) (36-Item Short Form Health
      Survey). Secondary outcome measures included self-efficacy, social support,
      patient and partner satisfaction with the appointment, and time available per
      patient. RESULTS: Two hundred seventy-two patients and 149 partners were
      included. Health-related QOL showed greater improvement in patients who had
      attended an SMA (mean difference 2.8 points, 95% confidence interval 0.0-5.7, p =
      0.05). Secondary outcomes showed small improvements in the control group for
      satisfaction with the appointment (p = 0.01). Neurologists spent less time per
      patient during the SMAs: mean 16 minutes (range 11-30) vs. 25 minutes (range 20
      30) for individual appointments. CONCLUSIONS: This study provides evidence that
      SMAs can improve aspects of QOL of patients with a chronic neuromuscular
      disorder. This could result in an alternative to individual appointments and
      improvements in both effectiveness and efficiency. Further research to optimize
      SMAs and to identify critical success factors seems warranted. These data extend
      evidence on SMAs for neurologic patients. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that for patients with chronic neuromuscular
      disorders, SMAs improve QOL as compared with individual medical appointments.

PMID- 24944258
TI  - Comment: can APOE genotyping predict cognitive damage from brain tumor therapy?

PMID- 24944259
TI  - Severe anemia in a patient with multiple sclerosis treated with natalizumab.

PMID- 24944260
TI  - Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo
      controlled, phase 3 trial.
AB  - OBJECTIVE: To determine whether droxidopa, an oral norepinephrine precursor,
      improves symptomatic neurogenic orthostatic hypotension (nOH). METHODS: Patients
      with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure
      autonomic failure, or nondiabetic autonomic neuropathy underwent open-label
      droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders,
      by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo.
      Outcome measures included patient self-ratings on the Orthostatic Hypotension
      Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom
      severity and symptom impact on daily activities. RESULTS: From randomization to
      endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa
      over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore
      favored droxidopa by 0.73 units (p = 0.010), with maximum change in
      "dizziness/lightheadedness." Improvement in symptom-impact subscore favored
      droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long
      time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg
      (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At
      endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and
      2.5% of placebo recipients. Adverse events reported in >= 3% of double-blind
      droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients
      discontinued double-blind treatment because of adverse events. CONCLUSIONS: In
      patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on
      daily activities, with an associated increase in standing systolic BP, and was
      generally well tolerated. CLASSIFICATION OF EVIDENCE: This study provides Class I
      evidence that in patients with symptomatic nOH who respond to open-label
      droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7
      days.

PMID- 24944261
TI  - Reporting standards for studies of diagnostic test accuracy in dementia: The
      STARDdem Initiative.
AB  - OBJECTIVE: To provide guidance on standards for reporting studies of diagnostic
      test accuracy for dementia disorders. METHODS: An international consensus process
      on reporting standards in dementia and cognitive impairment (STARDdem) was
      established, focusing on studies presenting data from which sensitivity and
      specificity were reported or could be derived. A working group led the initiative
      through 4 rounds of consensus work, using a modified Delphi process and
      culminating in a face-to-face consensus meeting in October 2012. The aim of this
      process was to agree on how best to supplement the generic standards of the STARD
      statement to enhance their utility and encourage their use in dementia research.
      RESULTS: More than 200 comments were received during the wider consultation
      rounds. The areas at most risk of inadequate reporting were identified and a set
      of dementia-specific recommendations to supplement the STARD guidance were
      developed, including better reporting of patient selection, the reference
      standard used, avoidance of circularity, and reporting of test-retest
      reliability. CONCLUSION: STARDdem is an implementation of the STARD statement in
      which the original checklist is elaborated and supplemented with guidance
      pertinent to studies of cognitive disorders. Its adoption is expected to increase
      transparency, enable more effective evaluation of diagnostic tests in Alzheimer
      disease and dementia, contribute to greater adherence to methodologic standards,
      and advance the development of Alzheimer biomarkers.

PMID- 24944263
TI  - Self-face hallucination evoked by electrical stimulation of the human brain.
AB  - OBJECTIVES: Self-face hallucination (autoscopic hallucination or AH) has been
      reported in patients with widespread brain damage or retrospectively after
      epileptic seizures. The neural basis and the self-processing operations
      underlying AH remain unknown. METHODS: We report the results of intracerebral
      electrical stimulations of the right medial occipitoparietal cortex (right
      precuneus and occipitoparietal sulcus) in 2 patients with epilepsy who underwent
      a stereo-EEG. RESULTS: Immediately after the onset of the stimulation, the 2
      patients reported seeing their current own face, facing themselves, in their left
      visual field. CONCLUSIONS: Our study shows that the medial occipitoparietal
      junction has a key role in generating AH. This region has been shown to have a
      central role in various self-processing operations and especially in self-face
      recognition. Our observations further reveal that this region is involved in a
      visual representation of our own face, which is generated during the pathologic
      phenomenon of AH. This visual representation of our own face may be useful for
      self-face recognition and social cognition processes involving judgment of self
      facial resemblance to others.

PMID- 24944262
TI  - APOE polymorphisms and cognitive functions in patients with brain tumors.
AB  - OBJECTIVE: The goal of this study was to assess whether the APOE epsilon4 allele
      and other APOE single nucleotide polymorphisms (SNPs) influence
      neuropsychological and neuroimaging outcomes in patients with brain tumors.
      METHODS: Two hundred eleven patients with brain tumors participated in the study.
      All patients completed standardized neuropsychological tests and provided a blood
      sample for APOE genotyping. Ratings of white matter abnormalities were performed
      on MRI scans. Patients were classified into 2 groups based on the presence (n =
      50) or absence (n = 161) of at least one APOE epsilon4 allele. Additional APOE
      SNPs were genotyped in a subset of 150 patients. RESULTS: Patients with at least
      one APOE epsilon4 allele had significantly lower scores in verbal learning and
      delayed recall, and marginally significant lower scores in executive function, in
      comparison to noncarriers of an epsilon4 allele. Patients with at least one
      epsilon4 allele and history of cigarette smoking had significantly higher scores
      in working memory and verbal learning than epsilon4 carriers who never smoked.
      Nine additional APOE SNPs were significantly associated with attention and
      executive and memory abilities. There were no significant differences between
      epsilon4 carriers and noncarriers on the extent of white matter abnormalities on
      MRI. CONCLUSIONS: The findings suggest that patients with brain tumors who are
      carriers of the APOE epsilon4 allele may have increased vulnerability to
      developing memory and executive dysfunction, and that additional SNPs in the APOE
      gene may be associated with cognitive outcome.

PMID- 24944264
TI  - Allopregnanolone levels and seizure frequency in progesterone-treated women with
      epilepsy.
AB  - OBJECTIVE: To determine whether allopregnanolone (AP) may mediate seizure
      reduction in progesterone-treated women with epilepsy. METHODS: The NIH
      Progesterone Trial compared the efficacy of adjunctive cyclic natural
      progesterone therapy vs placebo treatment of intractable seizures in 294
      subjects, randomized 2:1 to progesterone or placebo, stratified by catamenial vs
      noncatamenial designation. Treatments were compared on proportions of 50%
      responders, and changes in seizure frequency from 3 baseline to 3 treatment
      cycles. Serum AP levels were measured by radioimmunoassay from 155 women with
      intractable focal-onset seizures who had baseline and treatment-phase midluteal
      serum samples drawn each cycle for hormone measurements. RESULTS: There was no
      significant correlation between percentage changes in AP levels and seizure
      frequencies from baseline to treatment for either the catamenial or noncatamenial
      stratum. There was a significant correlation for the subset of subjects who
      showed a significantly greater responder rate in the post hoc analysis of the
      trial, i.e., subjects who had a 3-fold or greater increase in average daily
      seizure frequency perimenstrually compared with the midfollicular and midluteal
      phases (C1 >= 3: r = -0.442, p = 0.013, and specifically for C1 >= 3 progesterone
      treated subjects [r = -0.452, p = 0.035], but not other groups [C1 >= 3 placebo:
      r = -0.367; C1 <3 progesterone: r = 0.099; C1 <3 placebo: r = 0.131; p = not
      significant]). CONCLUSIONS: The findings support AP as a mediator of seizure
      reduction in progesterone-treated women who have a substantial level of
      perimenstrually exacerbated seizures.

PMID- 24944265
TI  - Seizure course during pregnancy in catamenial epilepsy.
AB  - OBJECTIVE: Our aim was to evaluate seizure course in catamenial epilepsy (CE) and
      noncatamenial epilepsy (NCE) during pregnancy. METHODS: We prospectively followed
      women referred to our Epilepsy Center for pregnancy planning to the end of the
      pregnancy. According to their seizure frequency variations across the menstrual
      cycle, all patients were divided into either the CE or the NCE group. Data on
      seizure frequency during pregnancy were collected for each patient and compared
      with seizure frequency during the pregestational 9 months. RESULTS: Fifty-nine
      women with CE and 215 with NCE were included. Forty-seven subjects (79.7%) with
      CE and 48 subjects (22.3%) with NCE remained seizure-free throughout pregnancy
      (odds ratio [OR] = 2.612, 95% confidence interval [CI] 1.901-3.323, p < 0.001),
      whereas 30 (50.8%) in the CE group and 18 (8.4%) in the NCE group had reduced
      seizure frequency during pregnancy (OR = 2.427, 95% CI 1.724-3.129, p < 0.001).
      Decreases in seizures >= 50% occurred in 26 women (44.1%) with CE and 14 women
      (6.5%) with NCE (OR = 2.426, 95% CI 1.679-3.173, p < 0.001). Multiple logistic
      regression models confirmed the significant role of catamenial pattern as
      predictor for better outcomes. CONCLUSIONS: Better seizure control during
      pregnancy in the catamenial group may be attributable to the absence of cyclical
      hormone variations and the increase in circulating progesterone levels. These
      data may have practical implications for therapeutic management of patients with
      CE during pregnancy.

PMID- 24944266
TI  - Feasibility of single-isocenter, multi-arc non-coplanar volumetric modulated arc
      therapy for multiple brain tumors using a linear accelerator with a 160-leaf
      multileaf collimator: a phantom study.
AB  - The feasibility of single isocenter, multi-arc non-coplanar volumetric modulated
      arc therapy (VMAT) for multiple brain tumors was studied using an Elekta Synergy
      linear accelerator with an Agility multileaf collimator and a Monaco treatment
      planning system. Two VMAT radiosurgery plans consisting of a full arc and three
      half arcs were created with a prescribed dose of 20 Gy in a single fraction.
      After dose delivery to a phantom, ionization chambers and radiochromic films were
      used for dose measurement. The first VMAT radiosurgery plan had nine targets
      inside the phantom, and the doses were measured by the chambers at two different
      points and by the films on three sagittal and three coronal planes. The
      differences between the calculated dose and the dose measured by a Farmer
      ionization chamber and a pinpoint ionization chamber were <1.00% and <2.30%,
      respectively, and the average pass rates of gamma indices among the six planes
      under each of 3%/3 mm and 2%/2 mm criteria were 98.6% and 92.6%, respectively.
      The second VMAT radiosurgery plan was based on a clinical 14 brain metastases.
      Differences between calculated and film-measured doses were evaluated on two
      sagittal planes. The average pass rates of the gamma indices on the planes under
      each of 3%/3 mm and 2%/2 mm criteria were 97.8% and 88.8%, respectively. It was
      confirmed that single-isocenter, non-coplanar multi-arc VMAT radiosurgery for
      multiple brain metastases was feasible using Elekta Synergy with Agility and
      Monaco treatment planning systems. It was further shown that film dosimetry was
      accurately performed for a dose of up to nearly 25 Gy. 

PMID- 24944267
TI  - Sex-dependent hypertension and renal changes in aged rats with altered renal
      development.
AB  - Numerous studies have evaluated blood pressure (BP) and renal changes in several
      models of developmental programming of hypertension. The present study examined
      to what extent BP, renal hemodynamic, and renal structure are affected at an old
      age in male and female animals with altered renal development. It also evaluated
      whether renal damage is associated with changes in cyclooxygenase (COX)-2 and
      neuronal nitric oxide synthase (NOS1) expression and immunoreactivity.
      Experiments were carried out in rats at 10-11 and 16-17 mo of age treated with
      vehicle or an ANG II type 1 receptor antagonist during the nephrogenic period
      (ARAnp). A progressive increment in BP and a deterioration of renal hemodynamics
      were found in both sexes of ARAnp-treated rats, with these changes being greater
      (P < 0.05) in male rats. The decrease in glomerular filtration rate at the oldest
      age was greater (P < 0.05) in male (74%) than female (32%) ARAnp-treated rats.
      Sex-dependent deterioration of renal structure was demonstrated in optical and
      electron microscopic experiments. COX-2 and NOS1 immunoreactivity were enhanced
      in the macula densa of male but not female ARAnp-treated rats. The present study
      reports novel findings suggesting that stimuli that induce a decrease of ANG II
      effects during renal development lead to a progressive increment in BP and renal
      damage at an old age in both sexes, but these BP and renal changes are greater in
      males than in females. The renal damage is associated with an increase of COX-2
      and NOS1 in the macula densa of males but not females with altered renal
      development. 

PMID- 24944268
TI  - Magnesium protects against cisplatin-induced acute kidney injury by regulating
      platinum accumulation.
AB  - Despite its success as a potent antineoplastic agent, ~25% of patients receiving
      cisplatin experience acute kidney injury (AKI) and must discontinue therapy.
      Impaired magnesium homeostasis has been linked to cisplatin-mediated AKI, and
      because magnesium deficiency is widespread, we examined the effect of magnesium
      deficiency and replacement on cisplatin-induced AKI in physiologically relevant
      older female mice. Magnesium deficiency significantly increased cisplatin
      associated weight loss and markers of renal damage (plasma blood urea nitrogen
      and creatinine), histological changes, inflammation, and renal cell apoptosis and
      modulated signaling pathways (e.g., ERK1/2, p53, and STAT3). Conversely, these
      damaging effects were reversed by magnesium. Magnesium deficiency alone
      significantly induced basal and cisplatin-mediated oxidative stress, whereas
      magnesium replacement attenuated these effects. Similar results were observed
      using cisplatin-treated LLC-PK1 renal epithelial cells exposed to various
      magnesium concentrations. Magnesium deficiency significantly amplified renal
      platinum accumulation, whereas magnesium replacement blocked the augmented
      platinum accumulation after magnesium deficiency. Increased renal platinum
      accumulation during magnesium deficiency was accompanied by reduced renal efflux
      transporter expression, which was reversed by magnesium replacement. These
      findings demonstrate the role of magnesium in regulating cisplatin-induced AKI by
      enhancing oxidative stress and thus promoting cisplatin-mediated damage.
      Additional in vitro experiments using ovarian, breast, and lung cancer cell lines
      showed that magnesium supplementation did not compromise cisplatin's
      chemotherapeutic efficacy. Finally, because no consistently successful therapy to
      prevent or treat cisplatin-mediated AKI is available for humans, these results
      support developing more conservative magnesium replacement guidelines for
      reducing cisplatin-induced AKI in cancer patients at risk for magnesium
      deficiency. 

PMID- 24944269
TI  - The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic
      nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in humans in
      the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2)
      inhibitors offers a new antidiabetic therapy via enhanced glucose excretion.
      Whether this strategy exerts beneficial effects on the development of type 2
      diabetic nephropathy is still largely unclear. We investigated the effects of the
      specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep<ob>/WiscJ (BTBR ob/ob)
      mice, which spontaneously develop type 2 diabetic nephropathy. In the first
      experiment, BTBR ob/ob mice received either a diet containing 300 ppm
      empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment,
      BTBR ob/ob mice received 1 MUg.kg body wt(-1).day(-1) ANG II to induce arterial
      hypertension and were separated into the same two diet groups for 6 wk. In both
      experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood
      glucose. Independently of hypertension, empagliflozin reduced albuminuria in
      diabetic mice. However, empagliflozin treatment affected diabetes-related
      glomerular hypertrophy, markers of renal inflammation, and mesangial matrix
      expansion only in BTBR ob/ob mice without hypertension. In summary, empagliflozin
      demonstrated significant antihyperglycemic effects, differentially ameliorating
      early features of diabetic nephropathy in BTBR ob/ob mice with and without
      hypertension.

PMID- 24944271
TI  - A modified transoral approach for carotid artery type Eagle syndrome: technique
      and outcomes.
AB  - OBJECTIVE: This article aimed to summarize our clinical experience with a
      standardized tonsil-sparing transoral surgical approach used for treatment of
      styloid process-carotid artery Eagle's syndrome. METHODS: Eleven consecutive
      patients, from 2007 to 2013, underwent surgical treatment to remove elongated
      styloid apophyses transorally. Outcomes were assessed in terms of intraoperative
      and postoperative complications and patients' evolution. RESULTS: No patient
      experienced any intraoperative or postoperative complications. All patients have
      been followed up to present and 10 of them have shown complete relief of the
      symptoms and improvement of functional ability. CONCLUSION: The tonsil-sparing
      transoral surgical approach described is suitable for treating patients with
      elongated styloid apophyses.

PMID- 24944272
TI  - Effects of radiofrequency thermal ablation on the nasal cycle measured using
      rhinomanometry.
AB  - OBJECTIVE: This study was designed to research the effects of radiofrequency
      thermal ablation (RFTA) surgery on the nasal cycle, with anterior rhinomanometry
      being used for assessment. METHODS: Thirty patients with inferior concha
      hypertrophy and 13 healthy volunteers were included in this study. An anterior
      rhinomanometry was performed on each of the patients before surgery and at 1
      month and 6 months after surgery, and on the volunteers in the control group,
      simultaneously. RESULTS: Nineteen of the 30 patients and 8 of the 13 healthy
      participants showed a distinct type of nasal cycle at different periods of
      measurement. The mean of the total nasal airflow of the patients was lower before
      RFTA surgery but increased at a rate of 71.07%, closer to the value of the
      control group, after RFTA surgery. After RFTA, the unilateral nasal airflow (fmin
      and fmax) values increased at ratios of 22.36% and 94.44%, respectively. The
      amplitude (fmax-fmin) showed a statistically significant decrease in the
      postoperative period (108.43 +/- 54.37), when compared with that of the
      preoperative period (202.80 +/- 81.24) (P < .01). CONCLUSION: We conclude that
      the RFTA is a useful method for treating inferior concha hypertrophy, because it
      positively affects the nasal physiology, increasing the total nasal airflow
      without changing the nasal cycle time.

PMID- 24944270
TI  - Voice, speech, and laryngeal features of primary Sjogren's syndrome.
AB  - OBJECTIVE: This study examined voice, speech, and laryngeal characteristics in
      primary Sjogren's syndrome (pSS). METHODS: Eleven patients (10 female, 1 male;
      mean [SD] age = 57 [14] years) from The University of Utah Division of
      Rheumatology provided connected speech and sustained vowel samples. Analyses
      included the Multi-Dimensional Voice Profile, the Analysis of Dysphonia in Speech
      and Voice, and dysphonia severity, speech clarity, and videolaryngostroboscopy
      ratings. RESULTS: Shimmer, amplitude perturbation quotient, and average
      fundamental frequency differed significantly from normative values (P < .01).
      Cepstral Spectral Index of Dysphonia values indicated mild-to-moderate dysphonia
      in connected speech (mean [SD] = 20.26 [8.36]) and sustained vowels (mean [SD] =
      16.91 [11.08]). Ratings of dysphonia severity and speech clarity using 10-cm
      visual analog scales suggested mild-to-moderate dysphonia in connected speech
      (mean [SD] = 2.11 [1.72]) and sustained vowels (mean [SD] = 3.13 [2.20]) and
      mildly reduced speech clarity (mean [SD] = 1.46 [1.36]). Videolaryngostroboscopic
      ratings indicated mild-to-moderate dryness and mild reductions in overall
      laryngeal function. Voice Handicap Index scores indicated mild-to-moderate voice
      symptoms (mean [SD] = 43 [23]). CONCLUSION: Individuals with pSS may experience
      dysphonia and articulatory imprecision, typically in the mild-to-moderate range.
      These findings have implications for diagnostic and referral practices in pSS.

PMID- 24944273
TI  - Complications after tracheal and cricotracheal resection and anastomosis for
      inflammatory and neoplastic stenoses.
AB  - OBJECTIVE: This study aimed to evaluate complications and success rates of
      tracheal resection and anastomosis (TRA) and cricotracheal resection and
      anastomosis (CTRA) in patients treated in 2 academic institutions. METHODS:
      Retrospective charts review of 137 patients submitted to TRA/CTRA. Fifty (36.5%)
      had neoplastic (group A) and 87 (63.5%) benign (group B) stenoses. Using
      univariate analysis, age, medical comorbidities, previous radiotherapy, type of
      TRA/CTRA, association with neck dissection and thyroidectomy, length of resected
      airway, and preoperative tracheotomy were evaluated to identify factors
      predictive of complications and outcomes. RESULTS: The mean length of resected
      airway was 2.7 and 3 cm in groups A and B, respectively. Overall decannulation
      and complication rates for group A were 96% and 36%, and 99% and 46% for group B,
      respectively. Length of airway resected and presence of preoperative tracheotomy
      had a statistically significant effect on major surgical complications. Age older
      than 70 and cardiovascular and pulmonary comorbidities were significantly
      associated with the incidence of major medical complications. No statistically
      significant difference was found considering the complication rates of group A
      versus group B. CONCLUSION: Even though the overall success rate of TRA/CTRA is
      high, it should always be regarded as a major surgical procedure with a non
      negligible incidence of complications.

PMID- 24944274
TI  - Recurrent cholesteatoma with massive extension to temporoparietal scalp: case
      report and literature review.
AB  - BACKGROUND: Cholesteatomas are locally destructive collections of epithelial
      debris arising from temporal bone squamous epithelium. Recurrences may occur
      after removal and are typically located within the temporal bone. OBJECTIVE: This
      study aimed to report a case of a massive, recurrent cholesteatoma with extension
      to temporoparietal scalp in a 37-year-old woman. METHODS: Case report with
      literature review. RESULTS: The patient underwent complete excision of a well
      circumscribed left temporal mass, intraoperatively identified to arise from the
      middle ear and to contain keratin debris. CONCLUSION: We report a case of
      recurrent cholesteatoma with massive extension to temporoparietal scalp. Clinical
      suspicion of recurrent cholesteatoma should remain in the differential diagnosis
      of temporal mass with prior history of cholesteatoma.

PMID- 24944276
TI  - A rapid and accurate technique for the identification of the recurrent laryngeal
      nerve.
AB  - OBJECTIVE: We studied the anatomic relationship between the recurrent laryngeal
      nerve (RLN) and the third tracheal ring, which was very important for rapid
      identification of RLN in our hands. METHODS: This study was initially performed
      using 8 fresh cadavers (4 female and 4 male). The transverse nerve location from
      the third trachea and the depth from its anterior surface were measured. We
      further observed the topography of RLN in relation to the trachea in 60 patients,
      between November 2008 and January 2011, at the Tri-Service General Hospital and
      Buddhist Tzu Chi General Hospital, Taipei Branch, Taiwan, with 46 lobo
      isthmectomies and 14 total thyroidectomies. The time spent in identifying the RLN
      was also recorded. RESULTS: Among cadaver groups, the transverse distance (width)
      and the vertical distance (depth) averaged 3.3 and 17.6 mm, respectively. Among
      the clinical cases, the width and depth averaged 4.4 and 14.6 mm, respectively.
      The depth measured in males was significantly deeper than that in females (22.3
      vs 13.2 mm) (P < .05). The time spent in identifying the RLN after starting
      dissection in the RLN triangle was not statistically significantly different
      between the cadaver group and the clinical group (10.6 +/- 5.7 seconds and 15.5
      +/- 17.7 seconds, respectively; P > .05). The median time was 9 and 10 seconds,
      respectively. There was no statistically significant side-to-side difference in
      terms of the time spent in searching for the RLN. CONCLUSION: Using the third
      ring as guidance, our inferior-superior technique offers an extra benefit in
      identifying the RLN safely and quickly, as compared to the conventional inferior
      approach.

PMID- 24944275
TI  - Case report: pharyngolaryngeal stenosis in a child due to caustic ingestion
      treated with transoral CO2 laser microsurgery.
AB  - Accidental caustic ingestion occurs mainly in the 2- to 3-year-old age group. Up
      to 33% of patients develop long-term complications that principally involve the
      gastroesophageal tract, whereas their occurrence at the level of pharyngeal and
      laryngeal structures is less frequent. When present, strictures are the main
      disorders that can be observed. In this pathological situation, surgery is the
      treatment of choice, and several procedures have been described. We report the
      history of a 3-year-old boy affected by pharyngolaryngeal stenosis due to
      accidental caustic ingestion. After careful diagnosis, the child underwent
      surgery by transoral CO2 laser. The patient had immediate improvement and
      restarted oral feeding 1 day after the surgical procedure. An analysis of
      diagnosis and treatment of this long-term complication is also presented. 

PMID- 24944277
TI  - The swing-door island flap canalplasty technique.
AB  - OBJECTIVE: This article describes a new canalplasty technique for the treatment
      of symptoms resulting from chronic refractory otitis externa. METHODS: We report
      on our experience using a swing-door island flap and a periosteal flap. Thirteen
      patients underwent treatment and a total of 19 ears were operated on. The range
      of preoperative symptoms was 3 to 22 years (mean length of symptoms = 12 years).
      RESULTS: The postoperative course in all the patients showed this to be a
      satisfactory treatment with no recurrence of symptoms. CONCLUSION: The swing-door
      island flap canalplasty technique is an effective surgical treatment in patients
      with refractory otitis externa.

PMID- 24944278
TI  - Prediction of hearing outcomes by multiple regression analysis in patients with
      idiopathic sudden sensorineural hearing loss.
AB  - OBJECTIVE: This study aimed to create a multiple regression model for predicting
      hearing outcomes of idiopathic sudden sensorineural hearing loss (ISSNHL).
      METHODS: The participants were 205 consecutive patients (205 ears) with ISSNHL
      (hearing level >= 40 dB, interval between onset and treatment <= 30 days). They
      received systemic steroid administration combined with intratympanic steroid
      injection. Data were examined by simple and multiple regression analyses. Three
      hearing indices (percentage hearing improvement, hearing gain, and posttreatment
      hearing level [HLpost]) and 7 prognostic factors (age, days from onset to
      treatment, initial hearing level, initial hearing level at low frequencies,
      initial hearing level at high frequencies, presence of vertigo, and contralateral
      hearing level) were included in the multiple regression analysis as dependent and
      explanatory variables, respectively. RESULTS: In the simple regression analysis,
      the percentage hearing improvement, hearing gain, and HLpost showed significant
      correlation with 2, 5, and 6 of the 7 prognostic factors, respectively. The
      multiple correlation coefficients were 0.396, 0.503, and 0.714 for the percentage
      hearing improvement, hearing gain, and HLpost, respectively. Predicted values of
      HLpost calculated by the multiple regression equation were reliable with 70%
      probability with a 40-dB-width prediction interval. CONCLUSION: Prediction of
      HLpost by the multiple regression model may be useful to estimate the hearing
      prognosis of ISSNHL.

PMID- 24944280
TI  - Correlation of maximum phonation time and vocal intensity with intraluminal
      esophageal and pharyngoesophageal pressure in total laryngectomees.
AB  - OBJECTIVE: This study aimed to correlate maximum phonation time, vocal intensity,
      and dynamic extension with intraluminal esophageal and pharyngoesophageal segment
      pressure during tracheoesophageal phonation. DESIGN: Prospective analysis.
      SETTING: Tertiary academic hospital. METHODS: The study was conducted on 20 total
      laryngectomees with alaryngeal speech and with secondary insertion of a
      tracheoesophageal prosthesis who were submitted to vocal recording of maximum
      phonation time and vocal intensity (minimum, habitual, and maximum). The
      participants were then submitted to manometry for the determination of the
      amplitude of intraluminal esophageal (proximal, middle, and distal) and
      pharyngoesophageal segment pressure during phonation. RESULTS: A significant
      positive correlation was detected between habitual vocal intensity and the middle
      (0.004) and distal (0.05) esophagus, in addition to a correlation of maximum
      intensity with the middle esophageal portion (0.03). Dynamic extension showed
      correlation with the amplitude of esophageal pressure. There was no significant
      correlation between the variables studied and pressure of the pharyngoesophageal
      segment or between maximum phonation time and esophageal pressure amplitude.
      CONCLUSION: The middle and distal regions of the esophagus were found to be
      compliant, permitting an adjustment of vocal intensity. There was no correlation
      between maximum phonation time and the amplitude of esophageal and
      pharyngoesophageal segment pressure.

PMID- 24944279
TI  - The hybrid lid crease approach to address lateral frontal sinus disease with
      orbital extension.
AB  - OBJECTIVE: This study aimed to describe the hybrid lid crease approach in
      conjunction with functional endoscopic sinus surgery (FESS) for lateral frontal
      sinus disease with orbital extension. STUDY DESIGN: Retrospective case review.
      METHODS: Patients undergoing hybrid lid crease approach with FESS for frontal
      sinus disease were reviewed retrospectively. Surgical indications consisted of
      inverting papilloma with extension into the frontal sinus (n = 1) and frontal
      sinus mucocele (n = 2). Inclusion criteria included presence of disease in the
      lateral frontal sinus with extension into the orbital space and erosion of the
      superior orbital rim. Preoperative and postoperative parameters included complete
      ophthalmologic exam, endoscopic exam, and computed tomography scan. RESULTS: We
      were able to access the frontal sinus and orbit in all 3 cases and address sinus
      pathology of the lateral frontal sinus and orbit using the lid crease approach
      with FESS. All patients had improvement in ophthalmologic symptoms and interval
      disease resolution and were satisfied with their postoperative lid crease
      incision. CONCLUSION: The lid crease approach offers direct access to the frontal
      sinus with minimal dissection through a well-hidden incision. In our case series
      of lateral frontal sinus pathology with orbital extension, the hybrid lid crease
      approach with FESS allowed complete eradication of disease without recurrence.

PMID- 24944281
TI  - Formulation and characterization of a porous, elastomeric biomaterial for vocal
      fold tissue engineering research.
AB  - OBJECTIVE: Biomaterials able to mimic the mechanical properties of vocal fold
      tissue may be particularly useful for furnishing a 3-dimensional microenvironment
      allowing for in vitro investigation of cell and molecular responses to vibration.
      Motivated by the dearth of biomaterials available for use in an in vitro model
      for vocal fold tissue, we investigated polyether polyurethane (PEU) matrices,
      which are porous, mechanically tunable biomaterials that are inexpensive and
      require only standard laboratory equipment for fabrication. METHODS: Rheology,
      dynamic mechanical analysis, and scanning electron microscopy were performed on
      PEU matrices at 5%, 10%, and 20% w/v mass concentrations. RESULTS: For 5%, 10%,
      and 20% w/v concentrations, shear storage moduli were 2 kPa, 3.4 kPa, and 6 kPa,
      respectively, with shear loss moduli being 0.2 kPa, 0.38 kPa, and 0.62 kPa,
      respectively. Storage moduli responded to applied frequency as a linear function.
      Mercury intrusion porosimetry revealed that all 3 mass concentrations of PEU have
      a similar overall percentage porosity but differ in pore architecture.
      CONCLUSION: Twenty-um diameter pores are ideal for cell seeding, and a range of
      mechanical properties indicates that the lower [corrected] mass concentration PEU
      formulations are best suited for mimicking the viscoelastic properties of vocal
      fold tissue for in vitro research.

PMID- 24944283
TI  - Linear growth deficit continues to accumulate beyond the first 1000 days in low-
      and middle-income countries: global evidence from 51 national surveys.
AB  - Growth faltering is usually assessed using height-for-age Z-scores (HAZs), which
      have been used for comparisons of children of different age and sex composition
      across populations. Because the SD (denominator) for calculating HAZ increases
      with age, the usefulness of HAZs to assess changes in height over time (across
      ages) is uncertain. We posited that population-level changes in height as
      populations age should be assessed using absolute height-for-age differences
      (HADs) and not HAZs. We used data from 51 nationwide surveys from low- and middle
      income countries and graphed mean HAZs and HADs by age. We also calculated annual
      changes in HAZs and HADs and percentage of total height deficit accumulated
      annually from birth to age 60 mo using both approaches. Mean HAZ started at -0.4
      Z-scores and dropped dramatically up to 24 mo, after which it stabilized and had
      no additional deterioration. Mean HAD started at -0.8 cm, with the most
      pronounced faltering occurring between 6 and 18 mo, similar to HAZ. However, in
      sharp contrast to HAZ, HAD curves had continued increases in the deficit of
      linear growth from 18 to 60 mo, with no indication of a leveling off. Globally,
      70% of the absolute deficit accumulated in height (HAD) at 60 mo was found to be
      due to faltering during the first "1000 days" (conception to 24 mo), but 30% was
      due to continued increases in deficit from age 2 to 5 y. The use of HAZ masks
      these changes because of age-related changes in SD. Therefore, HAD, rather than
      HAZ, should be used to describe and compare changes in height as children age
      because detecting any deficit compared with expected changes in height as
      children grow is important and only HAD does this accurately at all ages. Our
      findings support the current global programmatic momentum to focus on the first
      1000 d. Research is needed to better understand the dynamics and timing of linear
      growth faltering using indices and indicators that accurately reflect changes
      over ages and to identify cost-effective ways to prevent growth faltering and its
      consequences throughout the lifecycle. 

PMID- 24944282
TI  - Sugar-sweetened beverage consumption is associated with abdominal fat
      partitioning in healthy adults.
AB  - Abdominal adiposity, particularly visceral adipose tissue (VAT), is independently
      linked to the pathogenesis of diabetes and cardiovascular diseases. Emerging
      evidence suggests that greater intake of sugar-sweetened beverages (SSBs) may be
      associated with abnormal fat accumulation in VAT. We examined whether habitual
      SSB consumption and diet soda intakes are differentially associated with
      deposition of body fat. We conducted a cross-sectional analysis using previously
      collected data in 2596 middle-aged adults (1306 men and 1290 women) from the
      Framingham Heart Study Offspring and Third Generation cohorts. VAT and abdominal
      subcutaneous adipose tissue (SAT) were measured using multidetector computed
      tomography. Habitual intake of SSBs and diet soda was assessed by a validated
      food frequency questionnaire. We observed that SSB consumption was positively
      associated with VAT after adjustment for SAT and other potential confounders (P
      trend < 0.001). We observed an inverse association between SSB consumption and
      SAT (P-trend = 0.04) that persisted after additional adjustment for VAT (P-trend
      < 0.001). Higher SSB consumption was positively associated with the VAT-to-SAT
      ratio (P-trend < 0.001). No significant association was found between diet soda
      consumption and either VAT or the VAT-to-SAT ratio, but diet soda was positively
      associated with SAT (P-trend < 0.001). Daily consumers of SSBs had a 10% higher
      absolute VAT volume and a 15% greater VAT-to-SAT ratio compared with
      nonconsumers, whereas consumption of diet soda was not associated with either
      volume or distribution of VAT. 

PMID- 24944285
TI  - Oral doses of alpha-retinyl ester track chylomicron uptake and distribution of
      vitamin A in a male piglet model for newborn infants.
AB  - alpha-Retinol has utility in determining chylomicron trafficking of vitamin A to
      tissues given that it will not be recirculated in blood on retinol binding
      protein (RBP). In this study, alpha-retinol was used as a chylomicron tag to
      investigate short-term uptake from high-dose supplements given to piglets as a
      model for neonates. The distribution of orally administered alpha-retinol doses
      in liver and extrahepatic tissues was assessed at varying times after dosing.
      Male piglets (n = 24 per group) from vitamin A-depleted sows were orally given
      26.2 or 52.4 MUmol of alpha-retinyl acetate, the molar equivalent of 25,000 and
      50,000 IU of vitamin A, respectively. Tissues were collected and analyzed by
      HPLC. Lung (6.46 +/- 2.94 nmol/g), spleen (22.1 +/- 11.3 nmol/g), and adrenal
      gland (17.0 +/- 11.2 nmol/g) alpha-retinol concentrations peaked at 7 h after
      dosing, and, by 7 d, alpha-retinol was essentially cleared from these tissues
      (<=0.25 +/- 0.12 nmol/g). This demonstrates that the lung, spleen, and adrenal
      gland receive substantial vitamin A from chylomicra to maintain concentrations.
      Conversely, storage of alpha-retinol in the liver reached a plateau at 24 h (1.72
      +/- 0.58 MUmol/liver) and was retained through 7 d (2.10 +/- 0.38 MUmol/liver) (P
      > 0.05). This indicates that alpha-retinol was not substantially utilized locally
      in the liver nor transported out from the liver via RBP. In serum, the majority
      of alpha-retinol was in the ester form, which confirms that alpha-retinol does
      not bind to RBP but does circulate. alpha-Retinyl esters were detectable at 7 d
      in the serum but were not different from baseline. Collectively, these data
      suggest that crucial immune organs need constant dietary intake to maintain
      vitamin A concentrations because alpha-retinol was quickly taken up by tissues
      and decreased to baseline in all tissues except long-term storage in the liver. 

PMID- 24944284
TI  - n-3 PUFAs reduce T-helper 17 cell differentiation by decreasing responsiveness to
      interleukin-6 in isolated mouse splenic CD4+ T cells.
AB  - Cluster of differentiation 4(+) (CD4(+)) effector T-cell subsets [e.g., T-helper
      (Th) 1 and Th17] are implicated in autoimmune and inflammatory disorders such as
      multiple sclerosis, psoriasis, and rheumatoid arthritis. Interleukin (IL)-6 is a
      pleiotropic cytokine that induces Th17 polarization via signaling through the
      membrane-bound transducer glycoprotein 130 (GP130). Previously, we demonstrated
      that n-3 (omega-3) polyunsaturated fatty acids (PUFAs) reduce CD4(+) T-cell
      activation and differentiation into pathogenic Th17 cells by 25-30%. Here we
      report that n-3 PUFAs alter the response of CD4(+) T cells to IL-6 in a lipid
      raft membrane-dependent manner. Naive splenic CD4(+) T cells from fat-1
      transgenic mice exhibited 30% lower surface expression of the IL-6 receptor. This
      membrane-bound receptor is known to be shed during cellular activation, but the
      release of soluble IL-6 receptor after treatment with anti-CD3 and anti-CD28 was
      not changed in the CD4(+) T cells from fat-1 mice, suggesting that the decrease
      in surface expression was not due to ectodomain release. We observed a
      significant 20% decrease in the association of GP130 with lipid rafts in
      activated fat-1 CD4(+) T cells and a 35% reduction in GP130 homodimerization, an
      obligate requirement for downstream signaling. The phosphorylation of signal
      transducer and activator of transcription 3 (STAT3), a downstream target of IL-6
      dependent signaling, was also decreased by 30% in response to exogenous IL-6 in
      fat-1 CD4(+) T cells. Our results suggest that n-3 PUFAs suppress Th17 cell
      differentiation in part by reducing membrane raft-dependent responsiveness to IL
      6, an essential polarizing cytokine. 

PMID- 24944286
TI  - A "Roziah" by any other name: a simple Bayesian method for determining ethnicity
      from names.
AB  - Correct identification of ethnicity is central to many epidemiologic analyses.
      Unfortunately, ethnicity data are often missing. Successful classification
      typically relies on large databases (n > 500,000 names) of known name-ethnicity
      associations. We propose an alternative naive Bayesian strategy that uses
      substrings of full names. Name and ethnicity data for Malays, Indians, and
      Chinese were provided by a health and demographic surveillance site operating in
      Malaysia from 2011-2013. The data comprised a training data set (n = 10,104) and
      a test data set (n = 9,992). Names were spliced into contiguous 3-letter
      substrings, and these were used as the basis for the Bayesian analysis.
      Performance was evaluated on both data sets using Cohen's kappa and measures of
      sensitivity and specificity. There was little difference between the
      classification performance in the training and test data (kappa = 0.93 and 0.94,
      respectively). For the test data, the sensitivity values for the Malay, Indian,
      and Chinese names were 0.997, 0.855, and 0.932, respectively, and the specificity
      values were 0.907, 0.998, and 0.997, respectively. A naive Bayesian strategy for
      the classification of ethnicity is promising. It performs at least as well as
      more sophisticated approaches. The possible application to smaller data sets is
      particularly appealing. Further research examining other substring lengths and
      other ethnic groups is warranted. 

PMID- 24944287
TI  - Genetic variants related to height and risk of atrial fibrillation: the
      cardiovascular health study.
AB  - Increased height is a known independent risk factor for atrial fibrillation (AF).
      However, whether genetic determinants of height influence risk is uncertain. In
      this candidate gene study, we examined the association of 209 height-associated
      single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of
      European descent from the Cardiovascular Health Study, a prospective cohort study
      of older adults (aged >= 65 years) enrolled in 1989-1990. After a median follow
      up period of 13.2 years, 879 participants developed incident AF. The height
      associated SNPs together explained approximately 10% of the variation in height
      (P = 6.0 * 10(-8)). Using an unweighted genetic height score, we found a
      nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95%
      confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that
      genetically predicted height was strongly associated with AF risk (per 10 cm,
      hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly,
      for all models, the inclusion of actual height completely attenuated the genetic
      height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was
      independently associated with AF and may warrant future study. In conclusion, we
      found that genetic determinants of height appear to increase the risk of AF,
      primarily via height itself. This approach of examining SNPs associated with an
      intermediate phenotype should be considered as a method for identifying novel
      genetic targets.

PMID- 24944289
TI  - Rat-specific IgG and IgG4 antibodies associated with inhibition of IgE-allergen
      complex binding in laboratory animal workers.
AB  - OBJECTIVES: The relationship between exposure to rodent allergens and laboratory
      animal allergy is complex; at highest allergen exposures there is an attenuation
      of sensitisation and symptoms which are associated with increased levels of rat
      specific immunoglobulin (Ig)G and IgG4 antibodies. We set out to examine whether
      the increased levels of rat-specific IgG and IgG4 antibodies that we have
      previously observed at high allergen exposure in our cohort of laboratory animal
      workers play a functional role through blockage of the binding of IgE-allergen
      complex binding to CD23 receptors on B cells. METHODS: Cross-sectional survey of
      laboratory animal workers (n=776) in six UK pharmaceutical companies were
      surveyed. IgE-allergen complex binding to B cells was measured in 703 (97.9%)
      eligible employees; their exposure was categorised by either job group or number
      of rats handled daily. RESULTS: We observed a significant decrease in IgE
      allergen complex binding to B cells with increasing quartiles of both rat
      specific IgG and IgG4 antibodies (p<0.001). IgE-allergen complex binding to B
      cells was lower in workers with high allergen exposure, and significantly so
      (p=0.033) in the subgroup with highest exposures but no work-related chest
      symptoms. CONCLUSIONS: These findings demonstrate a functional role for rat
      specific IgG/G4 antibodies in laboratory animal workers, similar to that observed
      in patients treated with high dose immunotherapy who become clinically tolerant,
      suggesting a potential explanation for the attenuation of risk at highest
      allergen exposures.

PMID- 24944288
TI  - Accuracy of self-reported versus measured weight over adolescence and young
      adulthood: findings from the national longitudinal study of adolescent health,
      1996-2008.
AB  - Many studies rely on self-reports to capture population trends and trajectories
      in weight gain over adulthood, but the validity of self-reports is often
      considered a limitation. The purpose of this work was to examine long-term
      trajectories of self-reporting bias in a national sample of American youth. With
      3 waves of data from the National Longitudinal Study of Adolescent Health (1996
      2008), we used growth curve models to examine self-reporting bias in trajectories
      of weight gain across adolescence and early adulthood (ages 13-32 years). We
      investigated whether self-reporting bias is constant over time, or whether
      adolescents become more accurate in reporting their weight as they move into
      young adulthood, and we examined differences in self-reporting bias by sex,
      race/ethnicity, and attained education. Adolescent girls underreported their
      weight by 0.86 kg on average, and this rate of underreporting increased over
      early adulthood. In contrast, we found no evidence that boys underreported their
      weight either in adolescence or over the early adult years. For young men, self
      reports of weight were unbiased estimates of measured weight among all
      racial/ethnic and educational subpopulations over adolescence and early
      adulthood. 

PMID- 24944290
TI  - The effects of resting and exercise serum from children with cystic fibrosis on
      C2C12 myoblast proliferation in vitro.
AB  - Chronic systemic inflammation is a clinical symptom in children with cystic
      fibrosis (CF), but the effects on skeletal muscle development are unknown. The
      aims of this study were to determine (1) the effects of systemic factors from
      children with CF and healthy controls on myoblast proliferation, and (2) whether
      exercise serum can have an effect on proliferation in vitro. Eleven children with
      CF and 11 biological age-matched controls completed two 30-min bouts of cycling
      at an intensity set at 50% peak mechanical power. Serum samples were collected
      before exercise (REST), immediately following exercise (EX), and after 60 min of
      recovery (REC). Serum samples prepared in group-specific pools were used for cell
      culture experiments. C2C12 myoblasts were incubated in 5% serum and media for 1 h
      and then immediately harvested for protein and mRNA analysis, or incubated in
      growth media for 2 days to examine proliferation. C2C12 myoblasts treated with CF
      serum displayed greater proliferation phenotype than myoblasts treated with
      control serum. Proliferation did not change with EX or REC serum from children
      with CF compared to CF REST serum, while proliferation was increased with EX and
      REC serum from control compared to control REST serum. These findings suggest
      that systemic factors from children with CF at rest and after exercise can alter
      myoblast proliferation responses when compared to systemic factors from healthy
      children, which may have implications on skeletal muscle development. 

PMID- 24944291
TI  - A physiological increase in insulin suppresses muscle-specific ubiquitin ligase
      gene activation in fetal sheep with sustained hypoglycemia.
AB  - Decreased glucose transfer to the fetus is characteristic of pregnancies
      complicated by maternal under nutrition and placental insufficiency. Chronic
      experimental restriction of glucose transfer to the sheep fetus for the final 40%
      of gestation with a maternal insulin infusion (HG fetuses) results in fetal
      hypoglycemia, hypoinsulinemia, and decreased rates of fetal growth and protein
      accretion compared to controls (CON). Lower rates of fetal protein accretion are
      due to increased fetal protein breakdown and not decreased protein synthesis.
      However, the specific skeletal muscle pathways responsible for increased protein
      breakdown have not been determined. Nor has it been determined if low fetal
      glucose or insulin concentrations are more important for regulating these
      skeletal muscle protein breakdown pathways. We tested whether chronic restriction
      of glucose transfer to the fetus increased the ubiquitin-proteosome pathway or
      autophagy-lysosome pathway in fetal sheep skeletal muscle and found no evidence
      for an increase in the autophagy-lysosome pathway. However, HG fetuses had
      increase mRNA expression of MaFBx1 (twofold, P < 0.01) and a trend for increased
      mRNA expression of MuRF1 (P = 0.08) compared to CON. A subset of chronically
      hypoglycemic fetuses received an isoglycemic insulin infusion for the final 7
      days of the maternal insulin infusion (HG + INS fetuses) and had MaFBx1 and MuRF1
      mRNA concentrations similar to CON fetuses. These results demonstrate that
      fetuses exposed to sustained hypoglycemia have decreased protein accretion due to
      activation of the skeletal muscle ubiquitin-proteosome pathway and that a fetal
      hyperinsulinemic clamp can suppress this pathway even in the context of continued
      hypoglycemia. 

PMID- 24944292
TI  - Variable reactive hyperemia in normotensive strains of rat.
AB  - Previous studies from our laboratory report variation in nitric oxide (NO)
      dependent arterial pressure within the same strain of normotensive Sprague-Dawley
      rat dependent upon the commercial vendor supplying the rats. Clinical assessment
      of endothelial NO activity and endothelial function in general has used
      postocclusion, flow-mediated dilation (FMD). Therefore, this study was conducted
      to determine whether the reactive hyperemic response was different between two
      normotensive strains from two different suppliers, Sprague-Dawley (SD) and Wistar
      Kyoto (WKY) rats from Charles River (CR) and Harlan Laboratories (H),
      respectively. Rats were anesthetized and the femoral artery was occluded for 5
      min, with femoral blood flow measured continuously by use of an ultrasonic
      perivascular flow probe. The average area under the reactive hyperemic response
      curve (3-min duration) was not different between SD rats from CR (80 +/- 23
      mL/min?s; n = 6) and H (94 +/- 16 mL/min?s; n = 6). As previously reported, blood
      pressures were higher in the SD rats from H versus CR. WKY rats from both
      suppliers had significantly larger hyperemia; 371 +/- 67 versus 281 +/- 71
      mL/min?s (n = 5) for the CR and H WKY rats, respectively, but again, were not
      different between vendors. Blood pressures in WKY rats were similar between
      vendors. These results suggest that differences in NO bioactivity are not
      discernable with an adapted FMD protocol in the rat and that normotensive strains
      of rat can have large differences in reactive hyperemia despite having similar
      blood pressures. 

PMID- 24944293
TI  - Prevalence and Clinical Characteristics of Osteochondritis Dissecans of the
      Humeral Capitellum Among Adolescent Baseball Players.
AB  - BACKGROUND: The prevalence and clinical characteristics of osteochondritis
      dissecans (OCD) of the humeral capitellum among adolescent baseball players are
      unknown. PURPOSE: To determine the OCD prevalence in adolescent competitive
      baseball players and to investigate the clinical characteristics of these
      patients. STUDY DESIGN: Cross-sectional and case-control study; Level of
      evidence, 3. METHODS: A total of 2433 baseball players (mean age, 14.5 +/- 1.5
      years) belonging to junior high school and high school baseball clubs were
      enrolled. Players completed a questionnaire, and the elbow of each player's
      throwing arm was assessed by ultrasonography. Participants with abnormal results
      on ultrasonography were further examined through radiographic study. The OCD
      lesions were classified into stages based on radiographic results, and
      demographic data were compared between players with and without OCD lesions.
      RESULTS: Osteochondritis dissecans of the humeral capitellum was found in 82
      (3.4%) elbows by ultrasonography. Players with an OCD lesion began playing
      baseball at an earlier age (P = .016), had a longer duration of competitive play
      (P = .0013), and had experienced more present (P = .0025) and past (P < .0001)
      elbow pain compared with players without a lesion. There were no differences
      between the 2 groups in the position played (P = .26). Sixty-eight patients
      underwent further radiographic examination for OCD (radiography, computed
      tomography, magnetic resonance imaging). Of these players, 10 (14.7%) were
      classified as having stage I OCD (radiolucent stage); 26 (38.2%), stage II
      (fragmentation stage); 9 (13.2%), stage III (loose body stage); 9 (13.2%), stage
      IV (residual stage); and 14 (23.5%), stage V (postoperative stage). CONCLUSION:
      The prevalence of OCD of the humeral capitellum, including latent cases, was 3.4%
      among adolescent baseball players. Players with OCD lesions began playing
      baseball at earlier ages, had played for longer periods, and had experienced more
      elbow pain. The player's current baseball position may not be related to the
      existence of OCD lesions in adolescents.

PMID- 24944294
TI  - Clinical, Functional, and Morphological Evaluations of Posterior Cruciate
      Ligament Reconstruction With Remnant Preservation: Minimum 2-Year Follow-up.
AB  - BACKGROUND: Numerous posterior cruciate ligament (PCL) reconstruction techniques
      have evolved and have revealed satisfactory outcomes; however, the optimal
      operative method for PCL reconstruction remains controversial. HYPOTHESIS:
      Transtibial PCL reconstruction with a remnant preservation technique would result
      in successful clinical, radiological, functional, and morphological outcomes. In
      addition, it was hypothesized that the results of combined PCL and posterolateral
      corner (PLC) reconstruction would be comparable with those of isolated PCL
      reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total
      of 168 patients who underwent arthroscopic PCL reconstruction with or without
      reconstruction of the PLC between March 2006 and June 2011 were retrospectively
      reviewed. Ninety-two patients who met the inclusion criteria were enrolled, and
      47 of 92 patients who underwent combined PCL and PLC reconstruction were
      evaluated as a subgroup. The PLC was reconstructed using the single fibular sling
      method. The patients were assessed by means of the Lysholm score, International
      Knee Documentation Committee (IKDC) subjective knee score, and Tegner activity
      score. Stability was evaluated using a KT-2000 arthrometer and Telos device.
      Proprioception was assessed using the Biodex System. Follow-up magnetic resonance
      imaging (MRI) was performed in 34 patients, and second-look arthroscopic surgery
      was conducted in 36 patients. RESULTS: The minimum follow-up duration was 24
      months in all patients. Clinical outcomes and posterior instability improved
      significantly. The mean Lysholm score improved from 56.7 +/- 7.1 to 89.3 +/- 7.3,
      the mean IKDC subjective knee score improved from 53.3 +/- 9.6 to 86.2 +/- 6.1,
      and the mean Tegner activity score was 2.5 +/- 0.8 preoperatively and 5.1 +/- 1.3
      postoperatively (all P < .001). The mean side-to-side difference on posterior
      stress radiography with the Telos device improved significantly, decreasing from
      12.1 +/- 2.5 mm to 2.7 +/- 1.3 mm (P < .001). The mean side-to-side difference on
      varus stress radiography was reduced from 5.9 +/- 0.8 mm preoperatively to 1.3 +/
      1.0 mm after combined PCL and PLC reconstruction (P < .001). Postoperative
      proprioception recovered to a level similar to that of the uninvolved side, and
      MRI and second-look arthroscopic surgery showed a high rate of complete healing
      and synovialization in patients who underwent either isolated PCL reconstruction
      or combined PLC and PCL reconstruction. CONCLUSION: Transtibial PCL
      reconstruction with remnant preservation resulted in satisfactory clinical,
      functional, radiological, and morphological outcomes. The results of combined
      posterolateral rotatory instability were comparable with those for isolated PCL
      reconstruction with adequate PLC reconstruction.

PMID- 24944295
TI  - Deficits in glenohumeral passive range of motion increase risk of elbow injury in
      professional baseball pitchers: a prospective study.
AB  - BACKGROUND: Injuries to the elbow joint in baseball pitchers appear common. There
      appears to be a correlation between shoulder range of motion and elbow injuries.
      PURPOSE: To prospectively determine whether decreased ROM of the throwing
      shoulder is correlated with the onset of elbow injuries in professional baseball
      pitchers. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: For 8
      consecutive years (2005-2012), passive range of motion of both the throwing and
      nonthrowing shoulders of all major and minor league pitchers within a single
      professional baseball organization were measured by using a bubble goniometer
      during spring training. In total, 505 examinations were conducted on 296
      pitchers. Glenohumeral external rotation and internal rotation were assessed in
      the supine position with the arm at 90 degrees  of abduction and in the plane of
      the scapula. The scapula was stabilized per methods previously established. Total
      rotation was defined as the sum of external rotation and internal rotation.
      Passive shoulder flexion was assessed with the subject supine and the scapula
      stabilized per methods previously established. Elbow injuries and days missed
      because of elbow injuries were assessed and recorded by the medical staff of the
      team. Throwing and nonthrowing shoulder measurements were compared by using
      Student t tests; 1-tailed Fisher exact tests were performed to identify
      significant associations between shoulder motion and elbow injury. Nominal
      logistic regression was performed to determine the odds of elbow injury. RESULTS:
      Significant differences were noted during side-to-side comparisons within
      subjects. There were 49 elbow injuries and 8 surgeries in 38 players, accounting
      for a total of 2551 days missed. Neither glenohumeral internal rotation deficit
      nor external rotation insufficiency was correlated with elbow injuries. Pitchers
      with deficits of >5 degrees  in total rotation in their throwing shoulders had a
      2.6 times greater risk for injury. Pitchers with deficit of >=5 degrees  in
      flexion of the throwing shoulder had a 2.8 times greater risk for injury.
      CONCLUSION: Bilateral differences in shoulder total rotation and flexion had a
      significant effect on the risk for elbow injuries in pitchers. Clinicians need to
      be aware of these findings and plan preventive programs that address these issues
      in hopes of reducing elbow injuries.

PMID- 24944296
TI  - Improper trunk rotation sequence is associated with increased maximal shoulder
      external rotation angle and shoulder joint force in high school baseball
      pitchers.
AB  - BACKGROUND: In a properly coordinated throwing motion, peak pelvic rotation
      velocity is reached before peak upper torso rotation velocity, so that angular
      momentum can be transferred effectively from the proximal (pelvis) to distal
      (upper torso) segment. However, the effects of trunk rotation sequence on
      pitching biomechanics and performance have not been investigated. PURPOSE: The
      aim of this study was to investigate the effects of trunk rotation sequence on
      ball speed and on upper extremity biomechanics that are linked to injuries in
      high school baseball pitchers. The hypothesis was that pitchers with improper
      trunk rotation sequence would demonstrate lower ball velocity and greater stress
      to the joint. STUDY DESIGN: Descriptive laboratory study. METHODS: Three
      dimensional pitching kinematics data were captured from 72 high school pitchers.
      Subjects were considered to have proper or improper trunk rotation sequences when
      the peak pelvic rotation velocity was reached either before or after the peak
      upper torso rotation velocity beyond the margin of error (+/-3.7% of the time
      from stride-foot contact to ball release). Maximal shoulder external rotation
      angle, elbow extension angle at ball release, peak shoulder proximal force,
      shoulder internal rotation moment, and elbow varus moment were compared between
      groups using independent t tests (alpha < 0.05). RESULTS: Pitchers with improper
      trunk rotation sequences (n = 33) demonstrated greater maximal shoulder external
      rotation angle (mean difference, 7.2 degrees  +/- 2.9 degrees , P = .016) and
      greater shoulder proximal force (mean difference, 9.2% +/- 3.9% body weight, P =
      .021) compared with those with proper trunk rotation sequences (n = 22). No other
      variables differed significantly different between groups. CONCLUSION: High
      school baseball pitchers who demonstrated improper trunk rotation sequences
      demonstrated greater maximal shoulder external rotation angle and shoulder
      proximal force compared with pitchers with proper trunk rotation sequences.
      CLINICAL RELEVANCE: Improper sequencing of the trunk and torso alter upper
      extremity joint loading in ways that may influence injury risk. As such,
      exercises that reinforce the use of a proper trunk rotation sequence during the
      pitching motion may reduce the stress placed on the structures around the
      shoulder joint and lead to the prevention of injuries.

PMID- 24944297
TI  - Sir John Macpherson, the first but sometimes overlooked Professor of Psychiatry
      at the University of Sydney.
AB  - OBJECTIVE: To chronicle the creation of the Chair of Psychiatry at the University
      of Sydney, and the career and legacy, in New South Wales, of the first incumbent,
      Professor Sir John Macpherson CB MD FRCPE. CONCLUSIONS: The creation of the
      Chair, Macpherson's appointment, and his contributions to psychiatry in Sydney
      during the 52 months of his tenure, are well documented in contemporaneous
      sources and demonstrate that he was a very worthy Foundation Professor of
      Psychiatry at the University of Sydney. There are several possible reasons why
      Macpherson has been overlooked, including an erroneous statement in The World
      History of Psychiatry (1975) that William Siegfried Dawson, his successor from
      1927 to 1952, was the first Professor of Psychiatry.

PMID- 24944298
TI  - Improving collaboration: a qualitative assessment of inter-agency collaboration
      between a pilot Multisystemic Therapy Child Abuse and Neglect (MST-CAN) program
      and a child protection team.
AB  - OBJECTIVE: Child protection inter-agency collaboration is characterized by
      strengths and problems. Some literature notes positive attitudes and high trust
      between teams. However, difficulties with communication, confidentiality, roles,
      boundaries and divergent paradigms reconciling child protection and parent mental
      health needs have been documented. This study investigated whether a pilot model
      of intensive family intervention for maltreated children and associated intensive
      inter-agency cooperation delivered an effective collaboration. METHOD: At the
      completion of the pilot program, a child protection team was interviewed. A
      qualitative assessment by semi-structured group interview format of inter-agency
      collaboration was undertaken and evaluated by a thematic analysis. RESULTS: The
      analysis identified: strong endorsement of the collaborative model; no changes in
      perception of referred patients; changes in treatment approaches. No perceived
      conflict between child protection and parent mental health needs were noted.
      CONCLUSIONS: The changes noted may be due to the unique structure and functioning
      of the pilot Multisystemic Therapy Child Abuse and Neglect program, which
      encouraged high levels of team communication, strong client engagement,
      availability and intensive treatment of child and parent mental health problems.
      The implications for future collaborations are discussed as well as limitations
      of the study.

PMID- 24944299
TI  - The relationship between anger, childhood maltreatment, and emotion regulation
      difficulties in intimate partner and non-intimate partner violent offenders.
AB  - Violence is a significant public health problem, which has been linked to the
      primary emotion of anger. While several theoretical models have attempted to
      understand the relationship between anger and violence, empirical evidence to
      support these models and the psychological treatments that follow from them have
      been lacking. A newer model for understanding the relationship between anger and
      violence emphasizes the dual diatheses of childhood maltreatment and difficulties
      in emotion regulation as central to understanding the anger-violence
      relationship. Investigating the relationship between childhood maltreatment and
      anger experience and expression among 88 violent offenders referred for intimate
      partner or non-intimate partner violent offenses, results herein confirm that
      substantial childhood maltreatment is found among violent offenders, with
      differing patterns of abuse noted across groups. Furthermore, mediational
      analyses indicate that difficulties in emotion regulation mediate the
      relationship between childhood maltreatment and various aspects of anger
      experience and expression among both types of offenders. 

PMID- 24944300
TI  - Cardiac surgery with percutaneous interventional backup: a paradigm shift.

PMID- 24944301
TI  - Acute coronary syndromes without obstructive coronary atherosclerosis: the tiles
      of a complex puzzle.

PMID- 24944302
TI  - Moving beyond coronary stenosis: has the time arrived to address important
      physiological questions not answered by fractional flow reserve alone?

PMID- 24944303
TI  - Percutaneous transcatheter mitral valve replacement: an overview of devices in
      preclinical and early clinical evaluation.

PMID- 24944304
TI  - Percutaneous transjugular removal of an intracardial bone cement fragment after
      dorsal stabilization.

PMID- 24944305
TI  - Bilateral embolic protection devices for high-risk cardiac surgery in a patient
      with recent embolic stroke.

PMID- 24944306
TI  - Letter by Echavarria-Pinto and Escaned regarding article, "Thermodilution-derived
      coronary blood flow pattern immediately after coronary intervention as a
      predictor of microcirculatory damage and midterm clinical outcomes in patients
      with ST-segment-elevation myocardial infarction".

PMID- 24944307
TI  - Response to letter regarding article, "Thermodilution-derived coronary blood flow
      pattern immediately after coronary intervention as a predictor of
      microcirculatory damage and midterm clinical outcomes in patients with ST-segment
      elevation myocardial infarction".

PMID- 24944308
TI  - Letter by Ando et al regarding article, "Risk of acute kidney injury after
      percutaneous coronary interventions using radial versus femoral vascular access:
      insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium".

PMID- 24944309
TI  - Letter by Ozeke et al regarding article, "Risk of acute kidney injury after
      percutaneous coronary interventions using radial versus femoral vascular access:
      insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium".

PMID- 24944310
TI  - Response to letters regarding article, "Risk of acute kidney injury after
      percutaneous coronary interventions using radial versus femoral vascular access:
      insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium".

PMID- 24944311
TI  - Letter by Giblett and Hoole regarding article, "Remote ischemic postconditioning
      during percutaneous coronary interventions: remote ischemic postconditioning
      percutaneous coronary intervention randomized trial".

PMID- 24944312
TI  - Response to letter regarding article, "Remote ischemic postconditioning during
      percutaneous coronary interventions: remote ischemic postconditioning
      percutaneous coronary intervention randomized trial".

PMID- 24944315
TI  - Prostate cancer SubtyPINg biomarKers and outcome: is clarity emERGing?
AB  - Molecular prostate cancer subtypes have been proposed on the basis of mutually
      exclusive SPINK1 and ERG overexpression, with conflicting reports on their
      prognostic ability. Flavin and colleagues report that SPINK1 is neither
      prognostic nor absolutely mutually exclusive with ERG, raising important
      questions about prostate cancer molecular subtyping and prognostic biomarker
      evaluation.

PMID- 24944314
TI  - Lifetime prevalence of congenital heart disease in the general population from
      2000 to 2010.
AB  - BACKGROUND: Our objective was to obtain contemporary lifetime estimates of
      congenital heart disease (CHD) prevalence using population-based data sources up
      to year 2010. METHODS AND RESULTS: The Quebec CHD database contains 28 years of
      longitudinal data on all individuals with CHD from 1983 to 2010. Severe CHD was
      defined as tetralogy of Fallot, truncus arteriosus, transposition complexes,
      endocardial cushion defects, and univentricular hearts. We used latent class
      bayesian models combining case definitions from physician claims,
      hospitalization, and surgical data to obtain point and interval prevalence
      estimates of CHD in the first year of life, in children (<18 years of age) and in
      adults. We identified 107 559 CHD patients from 1983 to 2010. Prevalence of CHD
      in the first year of life was 8.21 per 1000 live births (95% confidence interval,
      7.47-9.02) from 1998 to 2005. In 2010, overall prevalence of CHD was 13.11 per
      1000 (95% confidence interval, 12.43-13.81) in children and 6.12 per 1000 (95%
      confidence interval, 5.69-6.57) in adults. CHD prevalence increased by 11% in
      children and 57% in adults from 2000 to 2010. Prevalence in the severe CHD
      subgroup increased by 19% (95% confidence interval, 17%-21%) in children and 55%
      (51%-62%) in adults. By 2010, adults accounted for 66% of the entire CHD
      population. CONCLUSIONS: With an increase of >50% in CHD prevalence since 2000,
      by 2010 adults accounted for two thirds of patients with severe and other forms
      of CHD in the general population. Our findings should inform allocation of
      resources and the planning of workforce needs for the predominantly adult CHD
      population.

PMID- 24944316
TI  - Intraperitoneal oxidative stress in rabbits with papillomavirus-associated head
      and neck cancer induces tumoricidal immune response that is adoptively
      transferable.
AB  - PURPOSE: How tumors evade or suppress immune surveillance is a key question in
      cancer research, and overcoming immune escape is a major goal for lengthening
      remission after cancer treatment. Here, we used the papillomavirus-associated
      rabbit auricular VX2 carcinoma, a model for studying human head and neck cancer,
      to reveal the mechanisms underlying the antitumorigenic effects of
      intraperitoneal oxidative stress following O3/O2-pneumoperitoneum (O3/O2-PP)
      treatment. EXPERIMENTAL DESIGN: Solid auricular VX2 tumors were induced in immune
      competent adult New Zealand White Rabbits. Animals were O3/O2-PP- or sham
      treated, after which they underwent tumor ablation upon reaching no-go criteria.
      CD3(+) tumor-infiltrating lymphocytes (TIL) were evaluated by
      immunohistochemistry, and expression levels of 84 immune response genes were
      measured by quantitative real-time PCR. Adoptive transfer of peripheral blood
      leukocytes (PBL)-derived from animals with tumor regression-into control animals
      with progressing tumors was implemented to assess acquired tumor resistance
      functionally. RESULTS: Auricular VX2 tumors regressing after O3/O2-PP treatment
      exhibited increased levels of CD3(+) TILs; they also exhibited enhanced
      expression of genes that encode receptors involved in pattern recognition,
      molecules that are required for antigen presentation and T cell activation, and
      inflammatory mediators. Adoptive cell transfer of PBLs from donor rabbits with
      regressing tumors to recipient rabbits with newly implanted VX2 carcinoma
      resulted in acquired tumor resistance of the host and tumor regression.
      CONCLUSION: Intraperitoneal oxidative stress effectively converts the immune
      response against the papillomavirus-associated rabbit VX2 carcinoma from tumor
      permissive to tumoricidal and leads to a sustainable, adoptively transferable
      oncolytic immune response.

PMID- 24944317
TI  - eComment. Suggestions that may prevent internal mammary artery obstruction after
      thoracoscopic Nuss bar repair of pectus.

PMID- 24944318
TI  - eComment. Nuss pectus excavatum repair: a hurdle for the treatment of coronary
      disease.

PMID- 24944319
TI  - eComment. The influence of cardiopulmonary bypass time on the outcome.

PMID- 24944320
TI  - eComment. Everything changes even statistics: it is time to use bootstrapped
      confidence intervals?

PMID- 24944321
TI  - eComment. Right ventricular dysfunction in functional tricuspid regurgitation: a
      word of caution.

PMID- 24944322
TI  - eComment. Optimal management of chylothorax following oesophagectomy.

PMID- 24944323
TI  - eComment. Substernal goiter. Beware of the thyroidea ima artery.

PMID- 24944324
TI  - eComment. Ventricular pseudoaneurysms in postsurgical cardiac patients.

PMID- 24944325
TI  - Cardiac paraganglioma.

PMID- 24944326
TI  - Rare case of left ventricular haemangioma: multi-modal approach to diagnosis.

PMID- 24944327
TI  - Feeling dizzy? A giant incidental finding.

PMID- 24944328
TI  - Chest pain 9 months after interventional atrial septal defect occlusion: do not
      forget the worst!

PMID- 24944330
TI  - Rationale for remodelling annuloplasty to address functional tricuspid
      regurgitation during left-sided valve surgery.

PMID- 24944329
TI  - Heart failure in younger patients: the Meta-analysis Global Group in Chronic
      Heart Failure (MAGGIC).
AB  - AIM: Our understanding of heart failure in younger patients is limited. The Meta
      analysis Global Group in Chronic Heart Failure (MAGGIC) database, which consisted
      of 24 prospective observational studies and 7 randomized trials, was used to
      investigate the clinical characteristics, treatment, and outcomes of younger
      patients. METHODS AND RESULTS: Patients were stratified into six age categories:
      <40 (n = 876), 40-49 (n = 2638), 50-59 (n = 6894), 60-69 (n = 12 071), 70-79 (n =
      13 368), and >=80 years (n = 6079). Of 41 926 patients, 2.1, 8.4, and 24.8% were
      younger than 40, 50, and 60 years of age, respectively. Comparing young (<40
      years) against elderly (>=80 years), younger patients were more likely to be male
      (71 vs. 48%) and have idiopathic cardiomyopathy (63 vs. 7%). Younger patients
      reported better New York Heart Association functional class despite more severe
      left ventricular dysfunction (median ejection fraction: 31 vs. 42%, all P <
      0.0001). Comorbidities such as hypertension, myocardial infarction, and atrial
      fibrillation were much less common in the young. Younger patients received more
      disease-modifying pharmacological therapy than their older counterparts. Across
      the younger age groups (<40, 40-49, and 50-59 years), mortality rates were low: 1
      year 6.7, 6.6, and 7.5%, respectively; 2 year 11.7, 11.5, 13.0%; and 3 years
      16.5, 16.2, 18.2%. Furthermore, 1-, 2-, and 3-year mortality rates increased
      sharply beyond 60 years and were greatest in the elderly (>=80 years): 28.2,
      44.5, and 57.2%, respectively. CONCLUSION: Younger patients with heart failure
      have different clinical characteristics including different aetiologies, more
      severe left ventricular dysfunction, and less severe symptoms. Three-year
      mortality rates are lower for all age groups under 60 years compared with older
      patients.

PMID- 24944331
TI  - Multiple factors predict the risk of spinal cord injury after the frozen elephant
      trunk technique for extended thoracic aortic disease.
AB  - OBJECTIVES: Spinal cord injury (SCI) after the frozen elephant trunk (FET)
      technique is more frequent than after endovascular aneurysm repair. This study
      aimed to identify risk factors of SCI after the FET technique. METHODS: We
      performed the FET technique for extended thoracic aortic disease in 224 patients
      (mean age, 72.1 +/- 10.9 years) from September 1997 to December 2011. The
      patients included those with acute type A aortic dissection (n = 103), acute type
      B aortic dissection (n = 30), chronic type B aortic dissection (n = 11) and
      thoracic atherosclerotic aneurysm (n = 80). Cerebrospinal fluid drainage (CSFD)
      was preoperatively performed for 18 elective cases with a high risk of spinal
      cord ischaemia from January 2003. RESULTS: Postoperative SCI was present in 8
      (3.5%), including complete paraplegia in 3, patients and transient or permanent
      paraparesis in 5 patients. CSFD was not a significant independent risk factor (P
      = 0.93) for SCI. Univariate logistic regression analysis identified pathology (P
      = 0.001), diabetes (P = 0.001), previous aortic operation (P = 0.003),
      atherosclerotic aorta (P = 0.003), distal position of the stent graft below the
      ninth thoracic vertebral level (Th9; P = 0.001) and low blood pressure after the
      operation (P = 0.009) as significant independent risk factors for SCI. Stepwise
      logistic regression analysis identified the distal position of the stent graft
      below Th9 (P = 0.003; odds ratio [OR], 15.167; 95% confidence interval [95% CI],
      2.568-89.578), mean pressure <70 mmHg (P = 0.008; OR, 11.470; 95% CI, 1.920
      68.546) and diabetes (P = 0.009; OR, 9.621; 95% CI, 1.779-52.032) as significant
      independent risk factors for SCI. CONCLUSIONS: There were multiple factors
      predicting the risk of SCI after the FET technique. Paraplegia may be prevented
      by avoiding deep insertion of the stent graft and by keeping blood pressure
      elevated after the operation.

PMID- 24944333
TI  - Brachybacterium ginsengisoli sp. nov., isolated from soil of a ginseng field.
AB  - A novel Gram-staining-positive, aerobic bacterium, designed DCY80(T), was
      isolated from soil of a ginseng field in the Republic of Korea. 16S rRNA gene
      sequence analysis revealed that strain DCY80(T) belonged to the genus
      Brachybacterium (95.8-98.2 % similarity) and was most closely related to
      Brachybacterium faecium DSM 4810(T) (98.2 %). Colonies were circular, entire, low
      convex, opaque and 0.5-1.0 mm in diameter after growth for 2 days on TSA at 30 
      degrees C. Growth occurred at 4-34  degrees C (optimum, 25  degrees C), at pH 5.0
      10.0 (optimum, pH 6.5-7.0) and in the presence of 0-7.0 % NaCl. Strain DCY80(T)
      produced siderophores and was sensitive to penicillin G, erythromycin, cefazolin,
      oleandomycin, ceftazidime, vancomycin, tetracycline, novobiocin, carbamicillin,
      rifampicin and neomycin. The DNA G+C content was 71.0 mol%. Levels of DNA-DNA
      relatedness between strain DCY80(T) and B. faecium DSM 4810(T), B.
      paraconglomeratum KCTC 9916(T), B. saurashtrense DSM 23186(T) and B.
      conglomeratum KCTC 9915(T) were 46.9+/-0.5, 28.9+/-0.6, 20.4+/-0.9 and 17.3+/-0.4
      %, respectively. The cell-wall peptidoglycan of strain DCY80(T) contained meso
      diaminopimelic acid as the diagnostic diamino acid. The menaquinones were MK-7
      (85.8 %) and MK-8 (14.2 %). The major cellular fatty acids were anteiso-C15 : 0
      (69.1 %) and anteiso-C17 : 0 (12.2 %). Phosphatidylglycerol,
      diphosphatidylglycerol, an unidentified glycolipid, two unidentified
      phospholipids and five unidentified polar lipids were found. On the basis of our
      phenotypic and genotypic analyses, strain DCY80(T) represents a novel species of
      the genus Brachybacterium, for which the name Brachybacterium ginsengisoli sp.
      nov. is proposed (type strain DCY80(T) = KCTC 29226(T) = JCM 19356(T)). 

PMID- 24944332
TI  - Prospective evaluation of long-term safety of dual-release hydrocortisone
      replacement administered once daily in patients with adrenal insufficiency.
AB  - OBJECTIVE: The objective was to assess the long-term safety profile of dual
      release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).
      DESIGN: Randomised, open-label, crossover trial of DR-HC or thrice-daily
      hydrocortisone for 3 months each (stage 1) followed by two consecutive,
      prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months
      (stage 3) at five university clinics in Sweden. METHODS: Sixty-four adults with
      primary AI started stage 1, and an additional 16 entered stage 3. Patients
      received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three
      daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and
      intercurrent illness (self-reported hydrocortisone use during illness). RESULTS:
      In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events
      with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1
      were not related to the cortisol exposure-time profile. The percentage of
      patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice
      daily hydrocortisone) decreased during stage 2, when all patients received DR-HC
      (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined,
      19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient
      years of DR-HC exposure. CONCLUSIONS: This long-term prospective trial is the
      first to document the safety of DR-HC in patients with primary AI and
      demonstrates that such treatment is well tolerated during 24 consecutive months
      of therapy.

PMID- 24944334
TI  - Reclassification of Desulfobacterium anilini as Desulfatiglans anilini comb. nov.
      within Desulfatiglans gen. nov., and description of a 4-chlorophenol-degrading
      sulfate-reducing bacterium, Desulfatiglans parachlorophenolica sp. nov.
AB  - A strictly anaerobic, mesophilic, sulfate-reducing bacterial strain (DS(T)),
      isolated from river sediment contaminated with volatile organic compounds, was
      characterized phenotypically and phylogenetically. Cells were Gram-reaction
      negative, non-motile short rods. For growth, optimum NaCl concentration was 0.9 g
      l(-1), optimum temperature was 30  degrees C and optimum pH was 7.2. Strain DS(T)
      utilized phenol, benzoate, 4-hydroxybenzoate, 4-methylphenol, 4-chlorophenol,
      acetate, butyrate and pyruvate as electron donors for sulfate reduction. Electron
      donors were completely oxidized. Strain DS(T) did not utilize sulfite,
      thiosulfate or nitrate as electron acceptors. The genomic DNA G+C content of
      strain DS(T) was 58.9 mol%. Major cellular fatty acids were iso-C14 : 0, anteiso
      C15 : 0 and C18 : 1omega7c. Phylogenetic analyses based on the 16S rRNA gene
      indicated its closest relatives were strains of Desulfobacterium anilini (about
      98-99 % sequence similarity) but the DNA-DNA hybridization value with
      Desulfobacterium anilini Ani1(T) was around 40 %. Although strain DS(T) and its
      relatives shared most phenotypic and chemotaxonomic characteristics, the
      utilization of 4-chlorophenol, the range of electron acceptors and the optimum
      growth conditions differed. Strain DS(T) is closely related to strains of
      Desulfobacterium anilini, but constitutes a different species within the genus.
      Based on phylogeny, phenotypic characteristics and chemotaxonomic
      characteristics, strain DS(T) and Desulfobacterium anilini were clearly different
      from strains of other species of the genus Desulfobacterium. We thus propose the
      reclassification of Desulfobacterium anilini within a new genus, Desulfatiglans
      gen. nov., as Desulfatiglans anilini comb. nov. We also propose Desulfatiglans
      parachlorophenolica sp. nov. to accommodate strain DS(T). The type strain is
      DS(T) ( = JCM 19179(T) = DSM 27197(T)). 

PMID- 24944335
TI  - Temperatibacter marinus gen. nov., sp. nov., a mesophilic bacterium isolated from
      surface seawater and description of Temperatibacteraceae fam. nov. in the class
      Alphaproteobacteria.
AB  - A Gram-stain-negative, motile, mesophilic, aerobic, rod-shaped bacterium, strain
      5-11(T), was isolated from surface seawater at Muroto city, Kochi prefecture,
      Japan. The strain exhibited a narrow growth temperature range of 20-30  degrees
      C. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain
      fell within the order Kordiimonadales in the class Alphaproteobacteria and was
      related most closely to the genus Kordiimonas (up to 91.2 % similarity to the
      type strains of species of the genus) but branched deeply from species of
      Kordiimonas. The major fatty acids were iso-C17 : 1omega9c, iso-C15 : 0, and C16
      : 1omega7c and/or iso-C15 : 0 2-OH. Ubiquinone-10 (Q-10) was detected as the sole
      isoprenoid quinone. The major polar lipids were phosphatidylethanolamine,
      phosphatidylglycerol and one unidentified aminolipid. Although strains of
      Kordiimonas have been shown to contain unidentified glycolipids, they were not
      detected from strain 5-11(T). The DNA G+C content of strain 5-11(T) was 44.3
      mol%, a value that was lower than those of strains of Kordiimonas (50-58 mol%)
      and was relatively low for the members of the class Alphaproteobacteria. On the
      basis of phenotypic, genotypic and chemotaxonomic data, it is proposed that
      strain 5-11(T) represents a novel species of a new genus, Temperatibacter marinus
      gen. nov., sp. nov., within a new family Temperatibacteraceae fam. nov. The type
      strain of Temperatibacter marinus is 5-11(T) ( = NBRC 110045(T) = LMG 28278(T)). 

PMID- 24944336
TI  - Martelella radicis sp. nov. and Martelella mangrovi sp. nov., isolated from
      mangrove sediment.
AB  - Two Gram-stain-negative, non-motile, rod-shaped bacterial strains, designated BM5
      7(T) and BM9-1(T) were isolated from soil of the root system of a mangrove
      forest. Phylogenetic analysis based on 16S rRNA gene sequences showed that the
      two isolates belong to the genus Martelella. The chemotaxonomic characteristics
      of these isolates included the presence of C19 : 0 cyclo omega8c and C18 :
      1omega7c as the major cellular fatty acids and Q-10 as the dominant ubiquinone.
      The genomic DNA G+C contents of strains BM5-7(T) and BM9-1(T) were 61.0 and 59.7
      mol% (HPLC method), respectively. The 16S rRNA gene sequence similarity between
      the two strains was 98.1 %, but DNA-DNA hybridization indicated 44 % relatedness.
      Strains BM5-7(T) and BM9-1(T) exhibited 16S rRNA gene sequence similarities of
      98.0-99.2 % and 97.7-98.1 %, respectively, with type strains of Martelella
      endophytica and Martelella mediterranea. Combined data from phenotypic,
      phylogenetic and DNA-DNA relatedness studies demonstrated that strains BM5-7(T)
      and BM9-1(T) are representatives of two novel species of the genus Martelella,
      for which the names Martelella radicis sp. nov. (type strain BM5-7(T) = DSM
      28101(T) = LMG 27958(T)) and Martelella mangrovi sp. nov. (type strain BM9-1(T) =
      DSM 28102(T) = LMG 27959(T)) are proposed. 

PMID- 24944337
TI  - Lactobacillus apinorum sp. nov., Lactobacillus mellifer sp. nov., Lactobacillus
      mellis sp. nov., Lactobacillus melliventris sp. nov., Lactobacillus kimbladii sp.
      nov., Lactobacillus helsingborgensis sp. nov. and Lactobacillus kullabergensis
      sp. nov., isolated from the honey stomach of the honeybee Apis mellifera.
AB  - We previously discovered a symbiotic lactic acid bacterial (LAB) microbiota in
      the honey stomach of the honeybee Apis mellifera. The microbiota was composed of
      several phylotypes of Bifidobacterium and Lactobacillus. 16S rRNA gene sequence
      analyses and phenotypic and genetic characteristics revealed that the phylotypes
      isolated represent seven novel species. One grouped with Lactobacillus kunkeei
      and the others belong to the Lactobacillus buchneri and Lactobacillus delbrueckii
      subgroups of Lactobacillus. We propose the names Lactobacillus apinorum sp. nov.,
      Lactobacillus mellifer sp. nov., Lactobacillus mellis sp. nov., Lactobacillus
      melliventris sp. nov., Lactobacillus kimbladii sp. nov., Lactobacillus
      helsingborgensis sp. nov. and Lactobacillus kullabergensis sp. nov. for these
      novel species, with the respective type strains being Fhon13N(T) ( = DSM 26257(T)
      = CCUG 63287(T)), Bin4N(T) ( = DSM 26254(T) = CCUG 63291(T)), Hon2N(T) ( = DSM
      26255(T) = CCUG 63289(T)), Hma8N(T) ( = DSM 26256(T) = CCUG 63629(T)), Hma2N(T) (
      = DSM 26263(T) = CCUG 63633(T)), Bma5N(T) ( = DSM 26265(T) = CCUG 63301(T)) and
      Biut2N(T) ( = DSM 26262(T) = CCUG 63631(T)). 

PMID- 24944338
TI  - Actinophytocola gilvus sp. nov., isolated from desert soil crusts, and emended
      description of the genus Actinophytocola Indananda et al. 2010.
AB  - An actinomycete strain, designated I12A-02593(T), was isolated from a desert soil
      crust sample collected in the Shapotou region of Tengger Desert, north-west
      China. The isolate grew well on International Streptomyces Project (ISP) media 2,
      3, 5 and 7, YS and Bennett's agar; it produced spherical bodies and formed clumps
      on the aerial mycelia on ISP 5 agar plates. Chemotaxonomically, the strain
      contained meso-diaminopimelic acid as the diagnostic diamino acid, arabinose and
      galactose as the diagnostic sugars in whole-cell hydrolysates, MK-9(H4) as the
      sole isoprenoid quinone, and iso-C16 : 0, iso-C16 : 0 2-OH and iso-C16 : 1 H as
      the major cellular fatty acids, without mycolic acids. The profile of the
      phospholipids mainly comprised diphosphatidylglycerol, phosphatidylethanolamine
      and hydroxyphosphatidylethanolamine. The genomic DNA G+C content was 70.1 mol%.
      The 16S rRNA gene sequence of strain I12A-02593(T) exhibited 96.4-97.4 %
      similarities with members of the genus Actinophytocola. In the phylogenetic tree
      based on 16S rRNA gene sequences, the isolate formed a robust cluster with
      Actinophytocola oryzae NBRC 105245(T), Aactinophytocola timorensis NBRC
      105524(T), Actinophytocola corallina NBRC 105525(T), Actinophytocola
      burenkhanensis NBRC 105883(T)and Actinophytocola xinjiangensis NBRC 106673(T).
      DNA-DNA hybridization values between strain I12A-02593(T) and the five species of
      the genus Actinophytocola were all less than 70 %. On the basis of the polyphasic
      taxonomy evidence, a novel species of the genus Actinophytocola is proposed, with
      the name Actinophytocola gilvus sp. nov. The type strain is I12A-02593(T) ( =
      CPCC 203543(T) = DSM 45828(T) = NBRC 109453(T) = KCTC 29165(T)). An emended
      description of the genus Actinophytocola is also provided. 

PMID- 24944339
TI  - Streptomyces iconiensis sp. nov. and Streptomyces smyrnaeus sp. nov., two
      halotolerant actinomycetes isolated from a salt lake and saltern.
AB  - The taxonomic positions of two novel actinomycetes, designated strains BNT558(T)
      and SM3501(T), were established by using a polyphasic approach. The organisms had
      chemical and morphological features that were consistent with their
      classification in the genus Streptomyces. The whole-cell hydrolysates of the two
      strains contained ll-diaminopimelic acid as the diagnostic diamino acid. The
      predominant menaquinones were MK-9(H6) and MK-9(H8) for strain BNT558(T) and MK
      9(H8) and MK-9(H6) for strain SM3501(T). Major fatty acids of the strains were
      anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipid profile of
      strain BNT558(T) contained diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol, one unidentified glycolipid and one unidentified
      aminophospholipid, while that of strain SM3501(T) consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylethanolamine, three unidentified atypical aminolipids, one
      unidentified aminolipid and two unidentified glycolipids. The G+C contents of the
      genomic DNA were 70.2 and 69.6 mol% for strains BNT558(T) and SM3501(T),
      respectively. 16S rRNA gene sequence data supported the classification of the
      isolates in the genus Streptomyces and showed that they formed two distinct
      branches within the genus. Based on almost-complete 16S rRNA gene sequences,
      strain BNT558(T) was related most closely to Streptomyces albiaxialis NRRL B
      24327(T) and strain SM3501(T) was related most closely to Streptomyces cacaoi
      subsp. cacaoi NBRC 12748(T). DNA-DNA relatedness between each of the isolates and
      its closest phylogenetic neighbours showed that they belonged to distinct
      species. The two isolates were readily distinguished from one another and from
      the type strains of the other species classified in the genus Streptomyces based
      on a combination of phenotypic and genotypic properties. Based on the genotypic
      and phenotypic evidence, strains BNT558(T) and SM3501(T) belong to two novel
      species in the genus Streptomyces, for which the names Streptomyces iconiensis
      sp. nov. (type strain BNT558(T) = KCTC 29198(T) = DSM 42109(T)) and Streptomyces
      smyrnaeus sp. nov. (type strain SM3501(T) = KCTC 29214(T) = DSM 42105(T)) are
      proposed, respectively. 

PMID- 24944340
TI  - Atopobium deltae sp. nov., isolated from the blood of a patient with Fournier's
      gangrene.
AB  - A Gram-stain-positive, obligately anaerobic, short rod, designated strain
      HHRM1715(T), was isolated from the blood of a patient with Fournier's gangrene,
      complicated by sepsis. On the basis of 16S rRNA gene sequence analysis, strain
      HHRM1715(T) was shown to belong to the genus Atopobium and was most closely
      related to Atopobium minutum (95 % similarity). The results of 16S rRNA-gene
      based phylogenetic analysis, cellular fatty acid analysis and differential
      biochemical tests, showed that strain HHRM1715(T) represented a novel species of
      the genus Atopobium. We therefore describe Atopobium deltae sp. nov. with
      HHRM1715(T) ( = LMG 27987(T) = CCUG 65171(T)) as the type strain and propose an
      emended description of the genus Atopobium with regard to the DNA G+C content. 

PMID- 24944342
TI  - Bifidobacterium faecale sp. nov., isolated from human faeces.
AB  - A novel strain, designated strain CU3-7(T), was isolated from faeces of a two
      week-old baby. The isolate was Gram-staining-positive, anaerobic and rod-shaped.
      Results from 16S rRNA gene sequence analysis revealed that strain CU3-7(T) was
      phylogenetically affiliated with members of the genus Bifidobacterium. Strain CU3
      7(T) showed the highest level of sequence similarity with Bifidobacterium
      adolescentis KCTC 3216(T) (98.4 %), followed by Bifidobacterium ruminantium KCTC
      3425(T) (97.9 %). Analysis of hsp60 sequences showed that strain CU3-7(T) was
      closely related to B. adolescentis KCTC 3216(T) (94.0 %) and B. ruminantium KCTC
      3425(T) (92.5 %). The DNA-DNA hybridization values with the closely related
      strains were all below the cut-off value for species delineation, 17.0 % with B.
      ruminantium KCTC 3425(T) and 14.9 % with B. adolescentis KCTC 3216(T). Fructose-6
      phosphate phosphoketolase activity was detected. The predominant cellular fatty
      acids were C16 : 0 (27.7 %), C18 : 1omega9c (27.4 %) and C18 : 1omega9c
      dimethylacetate (15.5 %). The DNA G+C content was 58.6 mol%. On the basis of
      polyphasic taxonomy, strain CU3-7(T) should be classified as the type strain of a
      novel species within the genus Bifidobacterium, for which the name
      Bifidobacterium faecale sp. nov. is proposed ( = KACC 17904(T) = JCM 19861(T)). 

PMID- 24944341
TI  - Polyphasic taxonomic revision of the Ralstonia solanacearum species complex:
      proposal to emend the descriptions of Ralstonia solanacearum and Ralstonia
      syzygii and reclassify current R. syzygii strains as Ralstonia syzygii subsp.
      syzygii subsp. nov., R. solanacearum phylotype IV strains as Ralstonia syzygii
      subsp. indonesiensis subsp. nov., banana blood disease bacterium strains as
      Ralstonia syzygii subsp. celebesensis subsp. nov. and R. solanacearum phylotype I
      and III strains as Ralstonia pseudosolanacearum sp. nov.
AB  - The Ralstonia solanacearum species complex has long been recognized as a group of
      phenotypically diverse strains that can be subdivided into four phylotypes. Using
      a polyphasic taxonomic approach on an extensive set of strains, this study
      provides evidence for a taxonomic and nomenclatural revision of members of this
      complex. Data obtained from phylogenetic analysis of 16S-23S rRNA ITS gene
      sequences, 16S-23S rRNA intergenic spacer (ITS) region sequences and partial
      endoglucanase (egl) gene sequences and DNA-DNA hybridizations demonstrate that
      the R. solanacearum species complex comprises three genospecies. One of these
      includes the type strain of Ralstonia solanacearum and consists of strains of R.
      solanacearum phylotype II only. The second genospecies includes the type strain
      of Ralstonia syzygii and contains only phylotype IV strains. This genospecies is
      subdivided into three distinct groups, namely R. syzygii, the causal agent of
      Sumatra disease on clove trees in Indonesia, R. solanacearum phylotype IV strains
      isolated from different host plants mostly from Indonesia, and strains of the
      blood disease bacterium (BDB), the causal agent of the banana blood disease, a
      bacterial wilt disease in Indonesia that affects bananas and plantains. The last
      genospecies is composed of R. solanacearum strains that belong to phylotypes I
      and III. As these genospecies are also supported by phenotypic data that allow
      the differentiation of the three genospecies, the following taxonomic proposals
      are made: emendation of the descriptions of Ralstonia solanacearum and Ralstonia
      syzygii and descriptions of Ralstonia syzygii subsp. nov. (type strain R 001(T) =
      LMG 10661(T) = DSM 7385(T)) for the current R. syzygii strains, Ralstonia syzygii
      subsp. indonesiensis subsp. nov. (type strain UQRS 464(T) = LMG 27703(T) = DSM
      27478(T)) for the current R. solanacearum phylotype IV strains, Ralstonia syzygii
      subsp. celebesensis subsp. nov. (type strain UQRS 627(T) = LMG 27706(T) = DSM
      27477(T)) for the BDB strains and Ralstonia pseudosolanacearum sp. nov. (type
      strain UQRS 461(T) = LMG 9673(T) = NCPPB 1029(T)) for the strains of R.
      solanacearum phylotypes I and III. 

PMID- 24944344
TI  - News feature: Seeing the ghostly universe.

PMID- 24944343
TI  - Unintentional drowning mortality, by age and body of water: an analysis of 60
      countries.
AB  - BACKGROUND: To examine unintentional drowning mortality by age and body of water
      across 60 countries, to provide a starting point for further in-depth
      investigations within individual countries. METHODS: The latest available three
      years of mortality data for each country were extracted from WHO Health
      Statistics and Information Services (updated at 13 November 2013). We calculated
      mortality rate of unintentional drowning by age group for each country. For
      countries using International Classification of Disease 10 (ICD-10) detailed 3 or
      4 Character List, we further examined the body of water involved. RESULTS: A huge
      variation in age-standardised mortality rate (deaths per 100 000 population) was
      noted, from 0.12 in Turkey to 9.19 in Guyana. Of the ten countries with the
      highest age-standardised mortality rate, six (Belarus, Lithuania, Latvia, Russia,
      Ukraine and Moldova) were in Eastern Europe and two (Kazakhstan and Kyrgyzstan)
      were in Central Asia. Some countries (Japan, Finland and Greece) had a relatively
      low rank in mortality rate among children aged 0-4 years, but had a high rank in
      mortality rate among older adults. On the contrary, South Africa and Colombia had
      a relatively high rank among children aged 0-4 years, but had a relatively low
      rank in mortality rate among older adults. With regard to body of water involved,
      the proportion involving a bathtub was extremely high in Japan (65%) followed by
      Canada (11%) and the USA (11%). Of the 13 634 drowning deaths involving bathtubs
      in Japan between 2009 and 2011, 12 038 (88%) were older adults aged 65 years or
      above. The percentage involving a swimming pool was high in the USA (18%),
      Australia (13%), and New Zealand (7%). The proportion involving natural water was
      high in Finland (93%), Panama (87%), and Lithuania (85%). CONCLUSIONS: After
      considering the completeness of reporting and quality of classifying drowning
      deaths across countries, we conclude that drowning is a high-priority public
      health problem in Eastern Europe, Central Asia, Japan (older adults involving
      bathtubs), and the USA (involving swimming pools).

PMID- 24944346
TI  - Spatial Heterogeneity in Cancer Control Planning and Cancer Screening Behavior.
AB  - Each state is autonomous in its comprehensive cancer control (CCC) program, and
      considerable heterogeneity exists in the program plans. However, researchers
      often focus on the concept of nationally representative data and pool
      observations across states using regression analysis to come up with average
      effects when interpreting results. Due to considerable state autonomy and
      heterogeneity in various dimensions-including culture, politics, historical
      precedent, regulatory environment, and CCC efforts-it is important to examine
      states separately and to use geographic analysis to translate findings in place
      and time. We used 100 percent population data for Medicare-insured persons aged
      65 or older and examined predictors of breast cancer (BC) and colorectal cancer
      (CRC) screening from 2001-2005. Examining BC and CRC screening behavior
      separately in each state, we performed 100 multilevel regressions. We summarize
      the state-specific findings of racial disparities in screening for either cancer
      in a single bivariate map of the 50 states, producing a separate map for African
      American and for Hispanic disparities in each state relative to whites. The maps
      serve to spatially translate the voluminous regression findings regarding
      statistically significant disparities between whites and minorities in cancer
      screening within states. Qualitative comparisons can be made of the states'
      disparity environments or for a state against a national benchmark using the
      bivariate maps. We find that African Americans in Michigan and Hispanics in New
      Jersey are significantly more likely than whites to utilize CRC screening and
      that Hispanics in 6 states are significantly and persistently more likely to
      utilize mammography than whites. We stress the importance of spatial translation
      research for informing and evaluating CCC activities within states and over time.

PMID- 24944347
TI  - Multiple imputation in quantile regression.
AB  - We propose a multiple imputation estimator for parameter estimation in a quantile
      regression model when some covariates are missing at random. The estimation
      procedure fully utilizes the entire dataset to achieve increased efficiency, and
      the resulting coefficient estimators are root-n consistent and asymptotically
      normal. To protect against possible model misspecification, we further propose a
      shrinkage estimator, which automatically adjusts for possible bias. The finite
      sample performance of our estimator is investigated in a simulation study.
      Finally, we apply our methodology to part of the Eating at American's Table Study
      data, investigating the association between two measures of dietary intake.

PMID- 24944349
TI  - The emergence of rational therapeutics from the traditions of clinical practice.

PMID- 24944348
TI  - Generalized Scalable Multiple Copy Algorithms for Molecular Dynamics Simulations
      in NAMD.
AB  - Computational methodologies that couple the dynamical evolution of a set of
      replicated copies of a system of interest offer powerful and flexible approaches
      to characterize complex molecular processes. Such multiple copy algorithms (MCAs)
      can be used to enhance sampling, compute reversible work and free energies, as
      well as refine transition pathways. Widely used examples of MCAs include
      temperature and Hamiltonian-tempering replica-exchange molecular dynamics (T-REMD
      and H-REMD), alchemical free energy perturbation with lambda replica-exchange
      (FEP/lambda-REMD), umbrella sampling with Hamiltonian replica exchange (US/H
      REMD), and string method with swarms-of-trajectories conformational transition
      pathways. Here, we report a robust and general implementation of MCAs for
      molecular dynamics (MD) simulations in the highly scalable program NAMD built
      upon the parallel programming system Charm++. Multiple concurrent NAMD instances
      are launched with internal partitions of Charm++ and located continuously within
      a single communication world. Messages between NAMD instances are passed by low
      level point-to-point communication functions, which are accessible through NAMD's
      Tcl scripting interface. The communication-enabled Tcl scripting provides a
      sustainable application interface for end users to realize generalized MCAs
      without modifying the source code. Illustrative applications of MCAs with fine
      grained inter-copy communication structure, including global lambda exchange in
      FEP/lambda-REMD, window swapping US/H-REMD in multidimensional order parameter
      space, and string method with swarms-of-trajectories were carried out on IBM Blue
      Gene/Q to demonstrate the versatility and massive scalability of the present
      implementation.

PMID- 24944350
TI  - A pilot study of single-dose azithromycin versus three-day azithromycin or single
      dose ceftriaxone for uncomplicated acute otitis media in children.
AB  - BACKGROUND: The pharmacokinetic profile of azithromycin supports its use as
      single-dose therapy for uncomplicated acute otitis media (AOM) in children.
      OBJECTIVE: This study was designed to (1) compare the safety of single-dose oral
      azithromycin, 3 daily doses of oral azithromycin, and a single dose of
      intramuscular ceftriaxone for the treatment of uncomplicated AOM in children, and
      (2) provide preliminary efficacy data to support initiation of a larger,
      comparative trial of single-dose azithromycin for the treatment of uncomplicated
      acute otitis media in children. METHODS: In this single-center pilot study,
      children with uncomplicated AOM were randomly assigned to receive single-dose
      oral azithromycin (30 mg/kg), 3-day oral azithromycin (10 mg/kg once daily), or
      single-dose intramuscular ceftriaxone (50 mg/kg). Tympanocentesis was performed
      before administration of the first dose, and clinical response was assessed on
      days 14-15 and 28-30. RESULTS: Between September 1995 and May 1997, 198 children
      (mean age, 2.5 years) were enrolled. All of the patients were evaluable for the
      safety and clinical intent-to-treat (ITT) analyses, and 98 were evaluable for the
      microbiologic ITT analysis. On day 14-15, rates of clinical success (cure or
      improvement) for the 3 treatment groups were: 62/64 (97%) for single-dose
      azithromycin, 60/63 (95%) for 3-day azithromycin, and 61/62 (98%) for single-dose
      ceftriaxone. On day 28-30, the corresponding clinical success rates were 61/65
      (94%), 61/66 (92%), and 62/64 (97%). For the 98 microbiologically evaluable
      patients, clinical success rates at day 14-15 were 28/30 (93%) for single-dose
      azithromycin, 31/35 (89%) for 3-day azithromycin, and 33/33 (100%) for single
      dose ceftriaxone. On day 28-30, the corresponding clinical success rates were
      27/30 (90%), 30/35 (86%), and 32/33 (97%). Treatment-related adverse event rates
      for single-dose azithromycin, 3-day azithromycin, and single-dose ceftriaxone
      were 10.6%, 9.1%, and 9.1%, respectively. CONCLUSION: In this pilot study
      comparing single-dose azithromycin, 3-day azithromycin, and single-dose
      ceftriaxone for the treatment of uncomplicated AOM in children, no differences
      were detected among the 3 regimens.

PMID- 24944351
TI  - Single-dose (30 mg/kg) azithromycin compared with 10-day amoxicillin/clavulanate
      for the treatment of uncomplicated acute otitis media: a double-blind, placebo
      controlled, randomized clinical trial.
AB  - BACKGROUND: The long half-life of azithromycin allows for single-dose oral
      therapy for acute otitis media (AOM). OBJECTIVE: This study was designed to
      compare the efficacy and tolerability of single-dose azithromycin with 10-day,
      twice-daily amoxicillin/clavulanate for the treatment of new-onset, uncomplicated
      AOM in children. METHODS: Children aged 6 months to 12 years with new-onset AOM
      were randomly assigned to receive either a single 30-mg/kg dose of azithromycin
      or standard-dose amoxicillin/clavulanate (45 mg/kg administered BID for 10 days)
      in a double-blind, double-placebo, multicenter clinical trial. The diagnosis of
      AOM was based on specific clinical signs and symptoms, and was confirmed by
      pneumatic otoscopy and acoustic reflectometry (level >=3). Clinical response was
      assessed on days 12-16 and 28-32. RESULTS: Mean (SD) age of children receiving
      azithromycin (n = 173) or amoxicillin/clavulanate (n = 173) was 2.7 (2.3) years
      and 3.4 (2.8) years, respectively, with 43% and 36% <=2 years of age. Most
      (53.2%) of the children were boys, and most (51.2%) were white. Clinical success
      rates (intent-to-treat) for azithromycin and amoxicillin/clavulanate,
      respectively, were 87% and 88% (95% CI, -9.2 to 6.5) on day 12-16 and 75% and 75%
      (95% CI, -10.2 to 10.5) on day 28-32. The incidences of treatment-related adverse
      events for azithromycin and amoxicillin/clavulanate were 16.8% and 22.5%,
      respectively. Corresponding rates of diarrhea were 6.4% and 12.7%, respectively.
      Vomiting, which was generally mild, occurred in 7 children in each group. One
      azithromycin patient and 5 amoxicillin/clavulanate patients discontinued
      treatment because of adverse events. The compliance rate for azithromycin was
      significantly higher than that for amoxicillin/clavulanate (99% vs 83%; P<0.001).
      CONCLUSIONS: In this trial comparing the efficacy of single-dose azithromycin (30
      mg/kg) with twice-daily amoxicillin/clavulanate (45 mg/kg) for the treatment of
      new-onset, uncomplicated AOM, no differences were detected between the 2
      regimens. Single-dose azithromycin was generally well tolerated and provides an
      alternative to conventional oral regimens for AOM.

PMID- 24944352
TI  - Treatment and treatment-related adverse events of type 2 diabetes mellitus in
      residents of long-term care facilities: a retrospective study.
AB  - BACKGROUND: In the United States, type 2 diabetes mellitus (DM) is most prevalent
      among adults aged >75 years. Judicious use of available therapies can improve
      plasma glucose concentration and reduce the risk for complications in elderly
      patients. However, selecting the appropriate medication for these patients is
      often challenging. OBJECTIVES: The goals of this retrospective study were to
      determine whether 1 or 2 medications were needed for the treatment of type 2 DM
      in elderly patients and to identify treatment-related adverse events (AEs).
      METHODS: The charts of residents of long-term care (LTC) facilities in New Jersey
      and Pennsylvania with a diagnosis of type 2 DM and receiving metformin, a
      sulfonylurea, rosiglitazone, or pioglitazone, either alone or in combination with
      insulin or another drug, were included. Data for laboratory values (including
      fasting plasma glucose [FPG] and serum creatinine concentration), body weight,
      and AEs were analyzed. RESULTS: The charts of 182 patients (121 women, 61 men)
      were included. The mean (SD) age of the women was 80.2 (10.2) years; and of the
      men, 73.7 (12.0) years. Many patients were switched from monotherapy to
      combination therapy due to a high FPG concentration. Sixty treatment-related AEs
      occurred in 60 patients; the pioglitazone and metformin groups had the highest
      incidence of AEs (8/11 [72.7%] patients and 21/48 [43.8%] patients, respectively)
      and the rosiglitazone group had the lowest (2/13 [15.4%] patients), although the
      number of patients in the pioglitazone and rosiglitazone groups was extremely
      low. CONCLUSIONS: In this study population of older patients, rosiglitazone
      monotherapy had favorable tolerability and appeared to be more effective than
      other therapies for type 2 DM. These results suggest that rosiglitazone
      monotherapy may be the safest and most effective of the 4 treatments for type 2
      DM in older patients. The rosiglitazone group was the only group that did not
      have a second medication added to control plasma glucose. However, additional
      studies are suggested to determine whether larger groups of older patients
      residing in LTC facilities would demonstrate similar results.

PMID- 24944353
TI  - Effects of verapamil slow release plus trandolapril combination therapy on
      essential hypertension.
AB  - BACKGROUND: Fixed-dose combination antihypertensive therapy has been recommended
      for patients with essential hypertension who are unresponsive to monotherapy or
      as a first-line treatment. OBJECTIVE: We investigated the effects of a fixed-dose
      combination of the phenylalkylamine-type calcium channel blocker verapamil slow
      release (SR)plus the angiotensin-converting enzyme inhibitor trandolapril on
      blood pressure (BP), serum lipid profile, urinary albumin excretion (UAE), left
      ventricular mass (LVM), and LVM index (LVMI), as well as the adverse events
      associated with this treatment. METHODS: Patients aged 30 to 65 years with mild
      to moderate essential hypertension were included in the study. All of the
      patients received capsules containing combination treatment with verapamil SR 180
      mg plus trandolapril 2 mg orally, daily for 12 weeks. Mean arterial pressure
      (MAP), systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) were measured
      at baseline and at 4, 8, and 12 weeks of treatment. Serum lipid profile, UAE,
      LVM, LVMI, and body mass index (BMI) were determined at baseline and at the end
      of the study period. All patients underwent electrocardiography and
      echocardiography at baseline and week 12. The primary end point of the study was
      to achieve an SBP/DBP <=140/<=90 mm Hg (ie, normotensive) during week 12. All
      adverse events were assessed as mild, moderate, or severe at each visit.
      According to the response rate at week 12, patients were divided into 2 groups:
      those who became normotensive (responders) or those who remained hypertensive
      (SBP/DBP >140/>90 mm Hg; nonresponders). RESULTS: Forty-one patients (29 women,
      12 men; mean [SD] age, 47.7 [7.8] years; mean [SD] BMI, 29.4 [3.5] kg/m(2)) were
      enrolled. The median durationof hypertension prior to enrollment was 5 months.
      Mean MAP, SBP, DBP, UAE, total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), LDL-C/highdensity lipoprotein cholesterol (HDL-C) ratio,
      LVM, LVMI, and BMI decreased significantly after 12 weeks of combination
      treatment; HR and triglyceride level did not change significantly. Treatment
      related adverse events occurred in 31.7% of patients, and none were severe or
      caused any patient to withdraw from the study. The most common adverse events
      were cough, constipation, headache, and dryness in the throat. Microalbuminuria,
      which may be a marker of endothelial dysfunction, was found in 7 (17.1%) patients
      at baseline and regressed significantly after 12 weeks. CONCLUSIONS: In this
      study population, the fixed-dose combination of verapamil-trandolapril was an
      effective and well-tolerated antihypertensive therapy. This combination
      significantly reduced MAP, BP, TC, LDL-C, LDL-C/HDL-C ratio, UAE, LVM, and LVMI.
      Also, microalbuminuria decreased after this treatment. Verapamil-trandolapril may
      be useful in preventing microalbuminuria and left ventricular hypertrophy in
      patients with essential hypertension.

PMID- 24944354
TI  - The Effects of a Standardized Herbal Remedy Made from a Subtype of Rosa canina in
      Patients with Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled
      Clinical Trial.
AB  - BACKGROUND: A standardized rose-hip powder produced from the seeds and husks of
      fruit from a subtype of Rosa canina has been reported to inhibit leukocyte
      functions that cause cell injury in osteoarthritis. OBJECTIVE: The aim of this
      study was to assess the impact of standardized rose-hip powder on mobility of the
      hip and knee joints, activities of daily living, quality of life, and pain in
      patients with osteoarthritis. METHODS: Patients with a diagnosis of
      osteoarthritis of either the hip or knee, verified on radiography, participated
      in this randomized, placebo-controlled, double-blind study. Half of the patients
      were given five 0.5-g capsules of standardized rose-hip powder twice daily for 4
      months, and the other half received identical placebo capsules twice daily for
      the same period. Mobility of the hip or knee was measured in both groups after
      the initial screening and again after 4 months of therapy. RESULTS: One hundred
      patients (65 women, 35 men; mean [SD] age, 65.2 [11.1] years) were divided into 2
      treatment groups of 50 patients each. Hip joint mobility improved significantly
      in the treatment group compared with the placebo group (P = 0.033). Similarly,
      pain decreased significantly in the treatment group compared with the placebo
      group (P = 0.035). Two patients (4%) from each group withdrew during the early
      stages of the trial for reasons not related to treatment. CONCLUSIONS: In this
      study population, standardized rose-hip powder reduced symptoms of
      osteoarthritis, as 64.6% of patients reported at least some reduction of pain
      while receiving treatment. Standardized rose-hip powder may improve hip flexion
      and reduce pain in patients with osteoarthritis.

PMID- 24944355
TI  - A review of the effects of medication delivery systems on treatment adherence in
      children with asthma.
AB  - BACKGROUND: A patient's adherence to an appropriate treatment regimen is
      necessary to minimize morbidity and mortality associated with childhood asthma.
      Many factors influence the success of treatment adherence. OBJECTIVE: The goal of
      this article was to examine the effect of the mode of medication delivery on the
      success of treatment adherence in children with asthma. METHODS: Relevant
      clinical studies were identified through a MEDLINE search of articles published
      from 1966 to 2002, using the search terms adherence, aerosol, asthma, children,
      compliance, dry powder inhaler, metered-dose inhaler, nebulizer, and pediatric.
      RESULTS: A relationship seems to exist between treatment adherence and the type
      of medication delivery system used in childhood asthma. The highest rates of
      adherence appear to be associated with oral medications. CONCLUSIONS: Clinicians
      should consider the mode of medication delivery as 1 factor that can influence
      the success of treatment adherence.

PMID- 24944356
TI  - Risperidone in children and adolescents with conduct disorder: a single-center,
      open-label study.
AB  - BACKGROUND: Risperidone is one of the most commonly used atypical antipsychotic
      drugs in the treatment of children and adolescents. However, the data about its
      use in children and adolescents with conduct disorder (CD) are limited.
      OBJECTIVE: The aim of this study was to investigate the effectiveness and
      tolerability of risperidone in controlling major symptoms of CD in children and
      adolescents diagnosed with attention deficit hyperactivity disorder (ADHD),
      oppositional defiant disorder (ODD), and severe CD. METHODS: Children and
      adolescents were eligible for this single-center, open-label study if they met
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM
      IV) diagnostic criteria for ADHD and ODD and also were diagnosed with severe CD.
      The patients were treated with risperidone in an open-label fashion for 8 weeks,
      starting at a daily dosage of 0.25 mg or 0.5 mg (depending on their body weight)
      in 2 divided doses. RESULTS: The study population comprised 21 children and
      adolescents (17 boys, 4 girls) with a mean (SD) age of 10.8 (3.6) years. The mean
      (SD) dosage of risperidone at the end of 8 weeks of treatment was 1.27 (0.42)
      mg/d (range, 0.75-2.0 mg/d). On the basis of the global improvement subscale of
      the Clinical Global Impression scale, 16 of 20 patients (80%) were classified as
      responders. Significant improvements were observed after risperidone treatment in
      the inattention, hyperactivity/impulsivity, ODD, and CD subscales of the Turgay
      DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale
      (parent and teacher forms). No severe adverse events were reported. CONCLUSIONS:
      The results of this study are consistent with previous findings and suggest that
      risperidone may be an effective and well-tolerated atypical antipsychotic drug
      for the treatment of children and adolescents with CD. However, further studies,
      particularly placebo-controlled and double-blinded, are needed to better define
      the clinical use of risperidone in children and adolescents with CD.

PMID- 24944357
TI  - Risk for osteoporosis in elderly nuns: need for better recognition and treatment.
AB  - BACKGROUND: The risk for osteoporosis in Catholic sisters (nuns) may be even
      higher than that of the general female population given their longer life
      expectancy (82.0 to 89.0 years vs 79.6 years for the average white woman) and the
      use of a traditional habit as a young adult, resulting in limited sun exposure
      (ie, exposure to vitamin D). OBJECTIVES: The aim of this study was to determine,
      in a group of elderly nuns attending an annual health screening day (Health
      Forum), how many met National Osteoporosis Foundation (NOF) treatment criteria
      using peripheral bone mineral density (BMD) measurements and risk factors; what
      proportion received adequate vitamin D; whether BMD was related to length of time
      that nuns wore a habit; and whether BMD measurement led to medical interventions.
      In addition, we compared the usefulness of calcaneal BMD with that of BMD at
      central sites for identification of those at risk for osteoporosis. METHODS: This
      cross-sectional study assessed BMD by calcaneal dual energy X-ray absorptiometry
      (DXA) and, for some participants, central DXA. A baseline questionnaire and
      follow-up mail survey also were included. RESULTS: Of the 230 nuns attending the
      Health Forum, 146 (63%) (mean age, 70 years; range, 48-90 years) participated in
      the study. Of these, 14% had calcaneal osteoporosis (T-score <-2.5) and 32% met
      NOF treatment criteria, indicating risk comparable to that of other
      postmenopausal American women. Sixty-four percent were receiving less than the
      recommended amount of vitamin D (>=400 IU/d for those aged <71 years and >=600
      IU/d for those aged >=71 years). Calcaneal BMD was inversely related to the
      length of time nuns had worn a habit. Fifty-six women subsequently underwent
      central DXA. Using a calcaneal T-score of -1.2 to identify those with central
      osteoporosis, sensitivity and specificity of 78% and 76%, respectively, were
      obtained. According to the mail survey, 11 of 42 respondents who had met NOF
      treatment criteria started new medications for osteoporosis. CONCLUSIONS: Elderly
      nuns are at substantial risk for osteoporosis. Most receive inadequate vitamin D.
      For nuns and others who may have limited access to central DXA measurement,
      peripheral measurements may help identify those in need of further intervention.
      Further efforts, in addition to BMD measurements, are necessary to ensure
      appropriate therapy for those who meet treatment criteria.

PMID- 24944358
TI  - A Single-Center, Open-Label, Randomized, Parallel-Group Study Assessing the
      Differences Between an Angiotensin II Receptor Antagonist and an Angiotensin
      Converting Enzyme Inhibitor in Hypertensive Patients with Congestive Heart
      Failure: The Research for Efficacy of Angiotensin II Receptor Antagonist in
      Hypertensive Patients with Congestive Heart Failure Study.
AB  - BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting
      enzyme inhibitors (ACEIs) have been used to treat congestive heart failure (CHF).
      According to a MEDLINE search, however, few studies are available on the clinical
      differences between ARBs and ACEIs in CHF. OBJECTIVE: To examine the clinical
      differences between an ARB (candesartan cilexetil) and an ACEI (lisinopril) in
      the treatment of CHF, we investigated exercise capacity, ventricular function,
      and neurohormonal levels in hypertensive patients with CHF before and after
      treatment with these agents. METHODS: Patients with symptoms of CHF (New York
      Heart Association functional class II-III and left ventricular ejection fraction
      [LVEF] <=45%) complicated by hypertension (systolic blood pressure [BP] >=140 mm
      Hg or diastolic BP >=90 mm Hg) were eligible for this single-center, open-label,
      randomized, parallel-group study. They were given either the ARB or the ACEI for
      24 weeks. A cardiopulmonary exercise test and echocardiography were performed.
      Clinical findings and cardiac events in addition to the CHF symptoms were
      investigated. Neurohormonal levels were measured before and after 24 weeks of
      treatment with the study drug. The primary end point of this study was exercise
      capacity, which was measured using peak oxygen consumption (VO2). RESULTS: Forty
      two patients with CHF were enrolled and 38 (28 men, 10 women; mean [SD] age, 69.0
      [8.2] years) completed the study. None of these patients had definite progression
      of the CHF symptoms. In the ARB-treated patients, mean (SD) peak VO2 (mL/min/kg)
      and LVEF (%) increased from 14.1 (2.9) to 15.3 (3.4) and from 34.4 (9.5) to 41.8
      (9.5), respectively. In the ACEI group, the peak VO2 did not change, but the LVEF
      (%) increased from 34.2 (10.2) to 40.4 (13.0). However, the differences between
      ARB and ACEI were not clarified because of the possibility of a small sample
      size. CONCLUSIONS: Although this study was not powered to show differences in
      efficacy between the ARB and ACEI in this study, our findings suggest that both
      ARB and ACEI had beneficial effects in hypertensive patients with CHF. Some
      unidentified differences in hemodynamic characteristics were found between the
      ARB and the ACEI groups.

PMID- 24944359
TI  - Pharmacokinetic and tolerability assessment of a pediatric oral formulation of
      pentoxifylline in kawasaki disease.
AB  - BACKGROUND: In infants and children, treatment of Kawasaki disease (KD) with high
      dose intravenous immunoglobulin (IVIG) and acetylsalicylic acid ([ASA] aspirin)
      diminishes inflammatory response and reduces the risk for coronary artery
      abnormalities. However, patients with high serum concentrations of tumor necrosis
      factor (TNF)-alpha, which is associated with vascular damage, may develop
      coronary artery lesions even with treatment. The hemorheologic agent
      pentoxifylline blocks the production of TNF-alpha and may be an appropriate
      adjunctive therapy to IVIG and ASA. OBJECTIVE: The objective of this study was to
      assess the pharmacokinetic characteristics and tolerability of a new oral syrup
      formulation of pentoxifylline as an adjunct to IVIG and ASA in the treatment of
      KD in children. METHODS: Hospitalized boys and girls aged 6 months to 5 years and
      who were diagnosed with KD within the first 10 days of illness were eligible.
      Patients were assigned to 1 of 4 pentoxifylline treatment groups, by dose level
      (dose levels 1, 2, 3, and 4: 10, 15, 20, and 25 mg/kg daily, respectively,
      divided into 3 doses). Six plasma samples collected at the time the first dose
      was administered, and 4 samples collected after administration of the last dose
      on study day 6, were assessed by high-performance liquid chromatography using
      noncompartmental and 1-compartment pharmacokinetic analyses for pentoxifylline
      and its active metabolite (M-1). TNF-alpha levels on days 1 and 6 were assessed
      using electroimmunoassay. RESULTS: Fourteen boys and 10 girls were enrolled. The
      mean age, body weight, and illness day at study entry were 34.5 months, 13.8 kg,
      and 6, respectively. Pentoxifylline exhibited nonlinear kinetic characteristics,
      with median area under the plasma concentration-time curve from time 0 to
      infinity(AUC0-infinity) values of 622, 3428, 8416, and 10,347 ng/mL . h for dose
      levels 1 to 4, respectively, on study day 1. Pentoxifylline noncompartmental oral
      clearance and volume of distribution were significantly lower, and dose
      normalized AUC0-infinity was significantly higher, for dose level 3 than dose
      level 1. M-1 parameters were not significantly different between dose levels. No
      accumulation of pentoxifylline or M-1 was noted. Fifteen of 24 patients (63%)
      reported mild to moderate adverse events that may or may not have been treatment
      related. Frequency and severity did not differ significantly between dose levels.
      CONCLUSIONS: In the children in this study, pentoxifylline was well tolerated at
      the doses studied. No notable differences in clinical outcomes were observed
      between dose levels, and dose levels 3 and 4 (20 and 25 mg/kg daily,
      respectively) resulted in similar exposure to both pentoxifylline and M-1. Future
      efficacy and tolerability studies should use a daily dose of 20 mg/kg of
      pentoxifylline in acute KD.

PMID- 24944360
TI  - Physicians' perceptions of factors influencing adherence to antibiotic
      prophylaxis in children with sickle cell disease.
AB  - BACKGROUND: Children with sickle cell disease (SCD) aged <5 years are at great
      risk for invasive infection with Staphylococcus pneumoniae and Haemophilus
      influenzae due to the inability of their spleen to protect against infection.
      OBJECTIVES: This study examined (1) physicians' perceptions of factors associated
      with adherence to antibiotic prophylaxis in children with SCD and (2) how
      physician characteristics are associated with these perceptions. METHODS: A
      MEDLINE search of the years 1996 to 2002, using the terms sickle cell disease,
      compliance, children, physician perceptions, and antibiotic prophylaxis, was
      done. A survey was developed using existing literature to assess physicians'
      perceptions of factors associated with adherence to antibiotic prophylaxis for
      SCD. The survey was sent to a stratified random sample of 375 pediatricians and
      all 125 practicing hematologists in North Carolina. They were given a Likert-type
      scale to assess their perceptions of factors that influence patients' adherence
      to antibiotic prophylaxis for SCD. Physician demographic information was
      collected using the North Carolina Health Professions Data Book. The demographic
      information was matched to the survey respondent and correlated with his or her
      responses. RESULTS: The response rate was 56.9%. Of the respondents, 60.9% were
      pediatricians, and 56.5% were in a practice with at least 1 patient aged <5 years
      with SCD. Physician race and practice specialty were significantly associated
      with factors physicians considered very important to adherence. CONCLUSIONS: Most
      physicians agree on many issues that affect adherence; however, significant and
      important differences exist, based on physician ethnicity. Physicians'
      perceptions of factors that affect adherence in this study did not always agree
      with factors demonstrated to actually affect adherence in SCD patients.
      Therefore, this study indicates a need for physician continuing-education
      programs that focus on factors that actually influence adherence of antibiotic
      prophylaxis and the racial/ethnic backgrounds of the providers in relation to the
      patient.

PMID- 24944361
TI  - Pharmacokinetic characteristics of caspofungin in two pediatric liver transplant
      patients.
AB  - BACKGROUND: The pharmacokinetic characteristics of the antifungal drug
      caspofungin have not been reported in children. OBJECTIVE: The aim of this study
      was to report limited caspofungin pharmacokinetic data for pediatric liver
      transplant patients. METHODS: Two pediatric liver transplant patients, aged 5
      years (not dialyzed) and 9 months (dialyzed), were assessed. Using a novel,
      validated, liquid-phase extraction with high-performance liquid chromatography,
      we measured plasma caspofungin concentrations from blood samples obtained within
      a 24-hour period after the patients were given 1 mg/kg IV of caspofungin.
      RESULTS: Noncompartmental analysis for the nondialyzed patient showed an
      elimination half-life of 10.7 hours, a volume of distribution of 0.11 L/kg, and a
      systemic clearance of 0.12 mL/min/kg. Liver enzyme activities increased briefly;
      the increase may have been due to concomitant graft rejection. For the dialyzed
      patient, the half-life was 11.7 hours, with an adjusted volume of distribution of
      0.18 L/kg and a systemic clearance of 0.24 mL/min/kg. No clinically relevant
      treatment-related adverse events were noted. CONCLUSIONS: Pharmacokinetic data
      found in the 2 patients in this study are similar to those reported in adults.
      Until more thorough data are published, caspofungin 1 mg/kg may be considered a
      reasonable, tolerable dose for children.

PMID- 24944362
TI  - Efficacy and tolerability of combination therapy with interferon-alfa plus
      ribavirin in patients with chronic hepatitis C virus infection: a single-center
      study in relapsers and nonresponders to previous treatment with high-dose
      interferon-alfa monotherapy.
AB  - BACKGROUND: In chronic hepatitis C virus (HCV) infection, interferon (IFN)
      monotherapy usually is carried out at doses of 3 to 6 million units (MU) 3 times
      per week, but treatment efficacy is low. OBJECTIVE: The aim of our study was to
      assess the efficacy and tolerability of IFN-alfa2b in combination with ribavirin
      in relapsers and nonresponders to high-dose IFN treatment (5 to 6 MU 3 times per
      week). We measured the biochemical and virologic responses to treatment and the
      risk for relapse during the 24 weeks following the end of treatment. METHODS:
      Patients with chronic HCV infection (relapsers and nonresponders to a previous
      treatment with high-dose IFN) received IFN-alfa2b, 3 MU 3 times per week, and
      ribavirin, 1000 or 1200 mg/d for 24 or 48 weeks. The patients were then followed
      up for an additional 24 weeks. Sustained response was defined as normal serum
      alanine aminotransferase (ALT) level and undetectable HCV RNA 24 weeks after
      treatment was stopped. RESULTS: Forty-three patients (32 men, 11 women; mean [SD]
      age, 45 [2] years; 10 relapsers, 33 nonresponders) were included in the study.
      Four patients were withdrawn from the study at week 4 of treatment because of
      treatment-related adverse events, and 1 dropped out. At the end of the treatment
      period, normalization of serum ALT levels and undetectable HCV RNA levels were
      seen in 58.1% and 30.2% of patients, respectively. No significant difference in
      virologic response at the end of treatment was found between nonresponders (10/33
      [30.3%]) to previous IFN therapy and relapsers (3/10 [30.0%]). At the end of
      follow-up, 3 (7.0%) treated patients had sustained response (2 nonresponders to
      the first IFN course and 1 relapser). All of the patients with sustained response
      were treated for 24 weeks. CONCLUSION: Based on the results of our study,
      combination therapy with IFN-alfa and ribavirin may be of value in a limited
      number of patients with chronic HCV infection who do not respond to, or relapse
      after, a first course of treatment with high-dose IFN monotherapy.

PMID- 24944363
TI  - Cilazapril treatment in a cohort of seven patients with congestive heart failure:
      a seven-year follow-up study.
AB  - BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEIs) have been
      shown to prolong life in patients with congestive heart failure (CHF), the
      prognosis of these patients remains poor. OBJECTIVE: The purpose of the study was
      to reevaluate a cohort of patients with CHF after 7 years of follow-up with
      cilazapril therapy to assess the renin-angiotensin system (RAS), anatomic and
      functional capacity of the heart, and aldosterone escape. METHODS: Surviving
      patients from a cohort hospitalized for CHF between January 1994 and December
      1994 who were treated with cilazapril in our center were included in this study.
      Exercise testing was carried out using the Kattus protocol, and breath-by-breath
      oxygen analysis, echocardiography, and hormonal analysis were done. RESULTS:
      Seven patients (5 men, 2 women; mean [SD] age, 70.6 [4.4]) were included in the
      study. Compared with the early effects (at 15 days) of cilazapril therapy, only
      mean (SD) peak exercise time decreased significantly at the 7-year follow-up (8.9
      [2.4] minutes vs 5.1 [1.9] minutes; P = 0.02). Mean (SD) anaerobic threshold (AT)
      oxygen consumption and AT ratio increased slightly from 15 days, although these
      changes were not statistically significant (12.86 [3.5] mL/kg.min vs 13.57 [2.6]
      mL/kg.min; 70.3% [7.7%] vs 78.9% [9.8%], respectively). Compared with the early
      effect of therapy, patients had slightly lower mean (SD) ejection fractions
      (EFs), but the decrease did not reach statistical significance (52% [4%] vs 48%
      [4%]). Aldosterone levels were within normal limits in all patients, and 2
      patients had increased RAS activity. CONCLUSIONS: In this study, the observed
      lack of aldosterone escape, as well as patient survival during ACEI therapy, may
      be due to selection bias of the surviving patients, who had better EFs and lack
      of aldosterone escape. Therefore, the remaining issue seems to be the selection
      of patients who will not show aldosterone escape during chronic ACEI treatment.

PMID- 24944364
TI  - Bayesian pharmacokinetic analysis of a gentamicin nomogram in neonates: a
      retrospective study.
AB  - BACKGROUND: Although gentamicin is used extensively within the first week of life
      for suspected sepsis in neonates, little is known about the performance of
      gentamicin dosing nomograms in this population. OBJECTIVE: The goal of our study
      was to retrospectively assess the performance of a gentamicin dosing nomogram in
      neonates given gentamicin during the first week after birth. METHODS: In this
      retrospective study, gentamicin therapeutic drug monitoring data were collected
      during routine clinical care for all neonates who were born in St. Boniface
      General Hospital (Winnipeg, Manitoba, Canada) between January 1999 and April 2001
      and given gentamicin during the first week after birth. We used Bayesian
      pharmacokinetic analysis to retrospectively assess the performance of our
      gentamicin dosing nomogram in neonates born at gestation ages <32 weeks, between
      32 and 34 weeks, and >34 weeks. Bayesian pharmacokinetic values for parameters
      within groups were compared and used to explore predicted peak and trough serum
      gentamicin concentrations based on the institutional dosing nomogram. RESULTS: In
      a total of 58 neonates, those neonates born at <=34 weeks' gestation had a weight
      normalized apparent volume of gentamicin distribution 1.6 times larger than
      infants born after 34 weeks' gestation (P<0.001), as identified by Bayesian
      analysis. Weight-normalized gentamicin clearance was 22% lower in the youngest
      age category (P<0.01). Only 33% of predicted peak serum gentamicin concentrations
      were >6 mg/L for neonates born at <=34 weeks' gestation, whereas 90% were
      therapeutic in neonates born at >34 weeks' gestation (P<0.001). With the present
      nomogram, the likelihood of an indication for adjustment of the dosing regimen
      was 12.4-fold higher (95% CI, 3.5-43.7) for those neonates born at <=34 weeks'
      gestation. CONCLUSIONS: These results have important clinical implications with
      regard to the advisability of determining peak serum gentamicin concentrations in
      neonates born at <=34 weeks' gestation. Sampling of peak serum concentrations is
      indicated in this population to avoid underdosing and potential loss of
      therapeutic efficacy.

PMID- 24944366
TI  - Editorial comment.

PMID- 24944365
TI  - Comparison of three oral rehydration strategies in the treatment of acute
      diarrhea in a tropical country.
AB  - BACKGROUND: The administration of hydrating solutions and early refeeding improve
      recovery for infants and children with diarrhea. OBJECTIVE: The aim of this study
      was to assess the efficacy of a low-osmolarity (30 mEq/L Na(+)) solution
      administered after the standard, high-osmolarity (90 mEq/L Na(+)) solution via a
      nasogastric tube (NGT) and followed by early refeeding to achieve more rapid body
      weight recovery in infants and children with acute diarrhea. METHODS: Infants and
      children aged <5 years with acute diarrhea and dehydration (body weight loss of
      >=10%) observed from January to August 2001 at Saint Camille Medical Center,
      Ouagadougou, Burkina Faso, were enrolled. Patients were randomized to 1 of 3
      treatment protocols. Patients in group A received, via NGT, rehydration with a
      high-osmolarity solution for 3 hours, followed by a low-osmolarity solution for
      at least 3 additional hours. Patients in group B were given only a low-osmolarity
      solution via NGT. In group C, rehydration was carried out using a high-osmolarity
      solution via NGT. RESULTS: Four thousand consecutively treated infants and
      children (2010 boys, 1990 girls; mean [SD] age, 3.5 [2.7] years) were enrolled.
      After the first 6 hours of infusion, 90% of the patients who had received the
      combined rehydration (group A) showed significant body weight recovery, versus
      80% and 79% of the patients in groups B and C, respectively. Stool output
      significantly decreased for group A compared with groups B and C (114 vs 125 and
      120 g/kg, respectively). Only 7% of the patients in group A required prolonged
      rehydration (>6 hours) with the low-osmolarity solution, versus 10% and 12% in
      groups B and C, respectively. A total of 3% of patients treated with combined
      rehydration required hospitalization, compared with 10% and 9% in groups B and C,
      respectively. At the end of infusion, 25% of the patients rehydrated only with a
      low-osmolarity solution showed poor body weight recovery and appeared lethargic,
      versus 10% in group A and 15% in group C. Patients who were rehydrated with a
      high-osmolarity solution showed symptoms of hypernatremia (serum Na(+)
      concentration >140 mEq/L). At the end of rehydration (>=6 hours), all patients
      recovered their previous body weight, partially or totally, and refeeding was
      begun. Rehydration and diet were continued at home, or in neighboring areas for
      those living far away. CONCLUSIONS: In this study population, the administration
      of a high-osmolarity solution followed by a low-osmolarity solution and early
      refeeding was effective in the treatment of acute diarrhea and was well
      tolerated.

PMID- 24944367
TI  - A multicenter, case-control study of the effects of antihypertensive therapy on
      orthostatic hypotension, postprandial hypotension, and falls in octo- and
      nonagenarians in residential care facilities.
AB  - BACKGROUND: Orthostatic hypotension, postprandial hypotension, and falls are
      considered to be adverse drug reactions of antihypertensive therapy in older
      people with comorbidities. Concerns regarding these adverse events may limit the
      use of antihypertensive agents in this group of people. OBJECTIVE: The aim of
      this study was to determine the relationship between antihypertensive therapy in
      octo- and nonagenarians and the risk for orthostatic hypotension, postprandial
      hypotension, and falls. METHODS: This was a case-control study of octo- and
      nonagenarians living in residential care facilities who were receiving
      antihypertensive therapy and a control group who were not receiving
      antihypertensive therapy. RESULTS: A total of 119 patients, 77 who were receiving
      regular antihypertensive therapy and 42 who were not taking any antihypertensive
      agents, were enrolled in the study. The prevalence of antihypertensive use,
      orthostatic hypotension, postprandial hypotension, and falls was high (65%, 29%,
      57%, and 45%, respectively). There were no associations between antihypertensive
      therapy and orthostatic hypotension, postprandial hypotension, and falls. When
      individual classes of antihypertensive agents were examined, the only observed
      association was a negative association (ie, a protective effect) between
      potassium-sparing diuretics and falls (odds ratio, 0.2; 95% CI, 0.04-1.0).
      CONCLUSION: Antihypertensive therapy was not associated with an increased risk
      for orthostatic hypotension, postprandial hypotension, or falls in this case
      control study of octo- and nonagenarians living in residential care facilities.

PMID- 24944368
TI  - Current therapeutic research.

PMID- 24944369
TI  - Editorial comment.

PMID- 24944370
TI  - Cholinesterase inhibitors for the treatment of Alzheimer's disease:: getting on
      and staying on.
AB  - BACKGROUND: Cholinesterase (ChE) inhibitors currently used in the treatment of
      Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective
      inhibitors, donepezil and galantamine, and the dual AChE and
      butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences
      in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic
      and pharmacodynamic properties, and these differences could significantly impact
      on safety, tolerability, and efficacy. OBJECTIVE: The aim of this article was to
      provide an overview of the ChE inhibitors widely used in AD, focusing on key
      pharmacologic differences among agents and how these may translate into important
      differences in safety, tolerability, and efficacy in clinical practice. METHODS:
      Using published literature collected over time by the author, a review was
      conducted, focusing on the pharmacology and clinical data of donepezil,
      galantamine, and rivastigmine. RESULTS: All ChE inhibitors have the potential to
      induce centrally mediated cholinergic adverse events (AEs), such as nausea and
      vomiting, if the dose is increased too rapidly or in increments that are too
      large. These AEs, which are most likely to occur during the "getting on," or dose
      escalation, phase of treatment, may result in patients discontinuing treatment
      early without achieving optimum therapeutic benefit. To reduce the incidence of
      these AEs, a slow dose-escalation schedule has been established in clinical
      practice, consisting of a "start low, go slow" procedure with a minimum of 4
      weeks between dose increases. After "getting on" treatment, maintaining treatment
      in the long term, or "staying on," may be achieved with good safety,
      tolerability, and sustained symptomatic efficacy across the key symptom domains
      (activities of daily living, behavior, and cognition). CONCLUSIONS: ChE
      inhibitors provide symptomatic benefit in AD across key symptom domains. Factors
      influencing the safety, tolerability, and efficacy of these agents in clinical
      practice include ChE enzymes inhibited, brain and brain-region ChE selectivity,
      and metabolism route. Class-specific cholinergic AEs can be minimized using slow,
      flexible dose escalation.

PMID- 24944371
TI  - Effects of fluvastatin on plasma levels of low-density lipoprotein subfractions,
      oxidized low-density lipoprotein, and soluble adhesion molecules: a twenty-four
      week, open-label, dose-increasing study.
AB  - BACKGROUND: Statins not only lower low-density lipoprotein (LDL) levels, but also
      have several antiarteriosclerotic effects (eg, decreasing arterial inflammation
      and arterial smooth muscle cell proliferation, as well as antioxidant effects).
      The relationship between the dose of statin and its effects on plasma LDL levels
      and other arteriosclerosis-related effects remains to be clarified. OBJECTIVE: We
      investigated the effect of a statin, fluvastatin, on plasma levels of lipoprotein
      subfractions, oxidized LDL (Ox-LDL), Ox-LDL immunoglobulin G (IgG), soluble
      adhesion molecules, reverse cholesterol transport (ie, transport of esterified
      high-density lipoprotein cholesterol [HDL-C] to triglyceride [TG]-rich
      lipoproteins by cholesteryl ester transfer protein [CETP] and reduction of plasma
      HDL-C levels), and on the intima-medial thickness (IMT) of the common carotid
      arteries. METHODS: Patients with nonfamilial type 2 hyperlipoproteinemia were
      eligible for this open-label, dose-increasing study. Fluvastatin 20 mg/d was
      administered for the first 12 weeks, and the daily dose was increased to 40 mg
      for the subsequent 12 weeks. Patients were examined at baseline and after 12 and
      24 weeks of treatment. Plasma lipoprotein subfractions were determined using
      sequential ultracentrifugation at 100,000g. The plasma levels of Ox-LDL, Ox-LDL
      IgG, CETP, and soluble adhesion molecules were measured using sandwich enzyme
      linked immunosorbent assay. The maximum IMT of the common carotid arteries was
      measured using sonography. RESULTS: The plasma levels of LDL cholesterol (LDL-C)
      and apolipoprotein (apo) B were reduced by 25% and 17%, respectively (P<0.001 for
      both), after 12 weeks of treatment with fluvastatin 20 mg/d; no further
      significant reductions in LDL were observed after increasing the daily dose to 40
      mg. Fluvastatin 20 mg/d for 12 weeks decreased plasma levels of intermediate
      density lipoprotein cholesterol, LDL-I-C, LDL-II-C, and LDL-III-C by 25%
      (P<0.01), 30% (P<0.001), 23% (P<0.01), and 20% (P = 0.02), respectively. No
      further significant reductions in these levels were observed after increasing the
      daily dose to 40 mg. The plasma levels of Ox-LDL decreased in a similar fashion
      to the plasma levels of LDL-C (P<0.001). However, plasma levels of Ox-LDL-IgG and
      soluble P-selectin did not decrease after 12 weeks of fluvastatin 20 mg/d, but
      did decrease significantly (both 22%) after the next 12 weeks of treatment with
      fluvastatin 40 mg/d (P<0.05). Plasma levels of intercellular adhesion molecule
      1and vascular cell adhesion molecule 1 and CETP mass were not altered by
      fluvastatin treatment. Significant changes in maximum IMT of the common carotid
      arteries were not seen throughout 24 weeks of fluvastatin treatment. CONCLUSIONS:
      In this patient population, fluvastatin 20 mg/d was sufficient to significantly
      reduce plasma levels of LDL, the 3 LDL subfractions, and Ox-LDL, but was not
      sufficient to reduce plasma levels of Ox-LDL-IgG and soluble P-selectin. It is
      important to check not only plasma lipoprotein levels but also other factors
      relating to arteriosclerosis during treatment with statins for the prevention and
      treatment of arteriosclerosis.

PMID- 24944373
TI  - Intravenous iron replacement with sodium ferric gluconate complex in sucrose for
      iron deficiency anemia in adults.
AB  - BACKGROUND: When oral iron replacement therapy is ineffective, IV or IM iron
      dextran products have been used successfully in many patients. However, adverse
      events, including urticaria, anaphylaxis, and death, sometimes are associated
      with the use of these products. OBJECTIVE: The aim of this study was to assess
      the efficacy and tolerability of sodium ferric gluconate complex (SFGC) in
      sucrose in the treatment of adults with iron deficiency anemia. METHODS: This was
      a single-center, open-label, uncontrolled study. Consecutive adults in need of IV
      iron replacement who experienced severe reactions to generic IV iron dextran and
      who had previously failed to respond to oral iron products were treated with a
      single dose of IV SFGC (312, 375, or 500 mg) infused over 2 hours. A second dose
      of SFGC could be administered 6 to 8 weeks later, if needed. RESULTS: Six
      patients (3 men, 3 women; mean [SD] age, 77.0 [10.4] years) were enrolled. All
      patients received a single-dose infusion of SFGC, and 2 patients received a
      second dose. No adverse events were observed at the lower doses (312 and 375 mg);
      however, both patients given the 500-mg dose reported transient nausea, and 1 had
      pruritus and the other had transient hypertension. CONCLUSION: The results of
      this study show that SFGC is a satisfactory alternative when IV iron replacement
      is needed by adults with iron deficiency anemia.

PMID- 24944372
TI  - Effects of a stimulant-free dietary supplement on body weight and fat loss in
      obese adults: a six-week exploratory study.
AB  - BACKGROUND: Obesity is a well-established risk factor for cardiovascular disease,
      diabetes, hyperlipidemia, hypertension, osteoarthritis, and stroke. Stimulants,
      such as ephedrine and caffeine and their herbal counterparts, have proved
      effective in facilitating body weight loss, but their use is controversial due to
      their undesired effects. Other nutraceuticals have shown moderate success in
      reducing body weight, whereas several other compounds have demonstrated little or
      no effect. Therefore, a tolerable and effective nutraceutical that can increase
      energy expenditure and/or decrease caloric intake is desirable for body weight
      reduction. OBJECTIVE: The primary purpose of this study was to assess the
      tolerability and effectiveness of a novel, stimulant-free, dietary supplement
      containing glucomannan, chitosan, fenugreek, Gymnema sylvestre, and vitamin C on
      body weight and fat loss and change in body composition in obese adults. METHODS:
      In this single-center, prospective, randomized, double-blind, placebo-controlled
      study conducted at the University of Guelph (Guelph, Ontario, Canada), obese
      adults (aged 20-50 years; body mass index [BMI], >=30 kg/m(2)) were randomized to
      the treatment or placebo group. The treatment group received 6 capsules of a
      dietary supplement containing a proprietary blend of glucomannan, chitosan,
      fenugreek, G sylvestre, and vitamin C daily for 6 weeks, and the placebo group
      received 6 capsules of rice flour daily for 6 weeks. Body weight; percentage of
      body fat; absolute fat mass; lean body mass; BMI; upper abdominal, waist, and hip
      circumference; and anthropometric measurements were recorded at baseline and at
      study end. Patients completed daily dietary intake records on days 1 to 3 and
      days 40 to 42. They also completed weekly activity logs throughout the study.
      RESULTS: Twenty-four subjects (mean [SD] age, 37.0 [8.2] years [range, 21
      48years]; mean [SD] BMI, 35.7 [6.2] kg/m(2) [range, 28.9-50.9 kg/m(2)]) were
      assigned to the treatment group (8 women, 4 men) or the placebo group (9 women,3
      men). Two subjects (8.3%; 1 patient [8.3%] from each group) dropped out for
      personal reasons unrelated to the study. No significant changes in the
      consumption of total calories; the percentage of calories ingested as
      carbohydrates, fat, or protein; or activity levels were found in either group
      throughout the study. Compared with the placebo group, the treatment group lost
      significantly more body weight (-2.3 kg vs 0.0 kg; P<0.01), percentage of body
      fat (-1.1% vs 0.2%; P<0.05), and absolute fat mass (-2.0 kg vs 0.2 kg; P<0.001).
      The treatment group also experienced a significantly greater reduction in upper
      abdominal circumference (-4.5 cm vs -0.7 cm), waist circumference (-4.1 cm vs 0.1
      cm), and hip circumference (-2.9 cm vs 0.6 cm) compared with the placebo group
      (P<0.05 for all). No significant changes in heart rate or blood pressure were
      found in either group. Both the treatment and the placebo were well tolerated.
      CONCLUSION: Within the context of this study, the novel combination of
      glucomannan, chitosan, fenugreek, G sylvestre, and vitamin C results in
      significant body weight and fat loss in obese adults. Disclosure: Derek E.
      Woodgate, MSc, is president and owner of NxCare Inc., which produces the dietary
      supplement containing glucomannan, chitosan, fenugreek, Gymnema sylvestre, and
      vitamin C (trade name Calorie-CareTM).

PMID- 24944375
TI  - Current therapeutic research.

PMID- 24944374
TI  - An antiregurgitation milk formula in the management of infants with mild to
      moderate gastroesophageal reflux.
AB  - BACKGROUND: Thickened milk formulas are used to treat infants with
      gastroesophageal reflux (GER), but these substances often increase the duration
      of reflux episodes and worsen symptoms, and they have been associated with
      diarrhea, constipation, and cough. OBJECTIVES: The aims of this study were to
      determine the efficacy of an antiregurgitation milk formula in the clinical and
      laboratory setting in infants with proved GER, to investigate any possible
      adverse events (cough and change in the number of bowel movements or the
      consistency of stools), and to identify its effects on height and body weight.
      METHODS: Infants with recurrent vomiting and GER who were not responsive to
      standard treatment were eligible for the study. Infants in the treatment group
      (group A) were managed for 4 weeks with a specific antiregurgitation milk formula
      (with cornstarch and an increased amount of casein), and those in the control
      group (group B) were given a standard milk formula. The number of episodes of
      vomiting, regurgitation, and cough, as well as the frequency and consistency of
      stool, height, and body weight were noted at least 10 days before and during the
      study. A second pH monitoring was performed after 4 weeks in both groups.
      RESULTS: Fifty-six infants (30 boys, 26 girls; mean [SD] age, 3.1 [1.2] months)
      were included in the study; 30.4% had mild GER; 44.6%, moderate GER; and 25.0%,
      severe GER. Significantly more infants in group A than in group B (50.0% vs
      14.3%, respectively) with mild or moderate GER had normal findings on the second
      pH monitoring (P<0.05). Changes in the reflux index and in the mean number of
      vomiting and regurgitation episodes were significantly different between the 2
      groups (P<0.05). No significant differences in changes in the mean number of
      bowel movements and cough events or in the consumption time of the 2 formulas
      were found between the 2 groups. CONCLUSION: Infants with mild or moderate GER
      can be managed effectively with this antiregurgitation milk formula. Improved
      clinical and laboratory findings were seen in the majority of infants, and the
      formula was well tolerated, without adverse events.

PMID- 24944376
TI  - Efficacy and tolerability of conventional nimesulide versus Beta-cyclodextrin
      nimesulide in patients with pain after surgical dental extraction: a multicenter,
      prospective, randomized, double-blind, double-dummy study.
AB  - BACKGROUND: Pain following extraction of an impacted third molar is widely used
      to assess analgesic efficacy, especially that of a single dose of a drug. The
      analgesic activity of conventional nimesulide (CN) has been documented in a
      variety of types of acute and chronic pain. Beta-cyclodextrin nimesulide (BN) is
      a new formulation in which nimesulide is included in a cyclodextrin molecule,
      which increases its solubility in water and its dilution rate, allowing extended,
      rapid absorption of the drug. OBJECTIVE: The aim of this study was to assess the
      efficacy and tolerability of a single dose of BN compared with CN in patients
      with pain following extraction of an impacted third molar. METHODS: This was a
      prospective, randomized, double-blind, double-dummy study conducted at 3
      dentistry centers in Venezuela. The patients were randomized to 1 of 2 groups.
      One group received a single dose of BN (400-mg tablet, equivalent to 100 mg of
      nimesulide); the other group received a single dose of CN (100-mg tablet). Both
      groups also received a placebo. The efficacy variables were (1) pain intensity
      (PI), assessed on a visual analog scale (VAS) at the following times: 0, 5, 10,
      15, 30, and 45 minutes and 1, 2, 4, 6, 8, 10, and 12 hours after drug
      administration; (2) time to first measurable difference in PI from baseline (PID)
      (PID >=1 cm on the VAS; ie, the beginning of analgesic action); (3) maximum PID
      (max PID); (4) sum of PIDs in the 12-hour observation period; (5) pain relief
      (PR), as rated on a 5-point scale; (6) maximum PR; and (7) sum of the PR scores
      in the 12-hour observation period (ie, total PR). For the tolerability analysis,
      all adverse events (AEs) were to be recorded, and the investigators were to
      assess whether each AE was drug related. RESULTS: Seventy-two patients were
      enrolled in the study. Of these, 62 patients (40 women, 22 men; mean [SD] age,
      20.1 [5.9] years) were assessed; 35 were treated with BN and 27 with CN. PI
      reduction was more rapid and greater in the BN group. The first measurable change
      in PI (PID >=1 on the VAS) was reached within 5 minutes by 39% and 15% of the
      patients in the BN and CN groups, respectively, and within 10 minutes by 52% and
      30% of the patients in the BN and CN groups, respectively. The max PID was
      reached <1 hour in 32% and 15% of patients in the BN and CN groups, respectively.
      No AEs were reported. CONCLUSIONS: In this study population, both BN and CN were
      similarly effective in relieving pain after extraction of an impacted third
      molar, and both drugs were well tolerated. PI changes were statistically
      significantly more rapid and greater with BN than CN.

PMID- 24944377
TI  - Efficacy and tolerability of delapril plus indapamide versus lisinopril plus
      hydrochlorothiazide combination treatments in mild to moderate hypertension: a
      multicenter, randomized clinical study.
AB  - BACKGROUND: Several studies have shown that antihypertensive monotherapy is
      commonly insufficient to control blood pressure (BP) in hypertensive patients and
      that concomitant use of >=2 drugs is necessary in ~50% of these patients. The
      combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic,
      delapril plus indapamide (D + I), has been shown to be effective and tolerable,
      with no interaction between the 2 components. Another widely used combination of
      ACE inhibitor and diuretic is lisinopril plus hydrochlorothiazide (L + H).
      OBJECTIVES: The aims of this study were to confirm the antihypertensive efficacy
      and tolerability of the fixed combination of D + I in mild to moderate
      hypertension, and to compare its therapeutic efficacy and tolerability with that
      of L + H. METHODS: The antihypertensive efficacy and tolerability of a fixed
      combination of D + I (30-mg + 2.5-mg tablets once daily) or L + H (20-mg + 12.5
      mg tablets once daily) in patients with mild to moderate hypertension were
      compared in a multinational, multicenter, randomized, 2-armed, parallel-group
      study. Eligible patients were aged 18 to 75 years and had a diastolic blood
      pressure (DBP) 95 to 115 mm Hg and a systolic blood pressure (SBP) <=180 mm Hg,
      both measured in the sitting position. After a single-blind, placebo run-in
      period of 2 weeks, patients were randomized to receive 1 of the 2 treatments for
      a 12-week period. The primary efficacy end point was the BP normalization rate
      (ie, the percentage of patients with a sitting DBP <=90 mm Hg) after 12 weeks of
      treatment. Secondary end points were as follows: (1) the responder rate (ie, the
      percentage of patients whose sitting DBP was reduced by >=10 mm Hg from baseline
      or had a DBP <=90 mm Hg after 12 weeks of treatment), (2) the percentage of
      patients with a DBP <=85 mm Hg, and (3) changes in sitting SBP and DBP after 4,
      8, and 12 weeks of treatment. RESULTS: A total of 159 hypertensive patients (88
      women, 71 men) were randomized to receive D + I (44 women, 36 men; mean [SD] age,
      53 [(11)] years) or L + H (44 women, 35 men; mean [SD] age, 55 [(10)] years). No
      significant between-group differences were found in any of the primary or
      secondary end points of the study. Both combinations induced a significant
      reduction in sitting DBP and SBP from baseline (P<0.001 for both groups at week
      12), without significant differences between the groups. Five mild to moderate
      adverse drug reactions (ADRs) occurred in each treatment group. No patient
      dropped out of the study because of an ADR. CONCLUSION: This study showed no
      difference between D + I and L + H interms of antihypertensive efficacy or
      tolerability in patients with mild to moderate hypertension.

PMID- 24944378
TI  - Early recovery properties of sevoflurane and desflurane in patients undergoing
      total hip replacement surgery.
AB  - BACKGROUND: The pharmacokinetic properties of sevoflurane and desflurane differ
      from those of other volatile anesthetics. For example, both agents allow more
      rapid emergence than traditional volatile anesthetics. However, few direct
      comparisons of the 2 agents have been made. OBJECTIVE: The aim of this study was
      to compare the early recovery properties of desflurane and sevoflurane in
      patients with American Society of Anesthesiologists physical status I or II
      undergoing total hip replacement (THR) surgery. METHODS: This open-label study
      was performed at the Department of Anesthesiology, Erciyes University School of
      Medicine, Kayseri, Turkey. Early recovery was assessed in the surgical suite by
      measuring the time to 50% decline of end-tidal volatile concentration of
      desflurane or sevoflurane; time to extubation, eye opening, orientation, and a
      modified Aldrete Scale (MAS) score >8 (ie, safe to discharge from the surgical
      suite); and time to discharge from the postanesthesia recovery room. RESULTS:
      Time to 50% decline of end-tidal volatile concentration of desflurane or
      sevoflurane, tracheal extubation, eye opening, orientation, and an MAS score >8
      occurred significantly more rapidly in the desflurane group than in the
      sevoflurane group (P<0.001). However, the groups did not differ significantly in
      duration of anesthesia; time to discharge from the postanesthesia recovery room;
      or incidences of nausea, vomiting, dizziness, and drowsiness in the first 24
      hours after anesthesia. CONCLUSIONS: In this study population, desflurane
      provided significantly more rapid early recovery than sevoflurane, but we did not
      find any beneficial effects of desflurane on intermediate recovery. The rapid
      emergence from anesthesia may facilitate more efficient surgical suite use and
      may be associated with more benefits after prolonged anesthesia. We suggest that
      both volatile agents may be acceptable anesthetics for use during THR surgery.

PMID- 24944379
TI  - Efficacy of different doses of lidocaine in the prevention of pain due to
      propofol injection: a randomized, open-label trial in 120 patients.
AB  - BACKGROUND: The incidence of pain due to propofol injection is high, but the most
      efficacious method of preventing this pain has not been identified. OBJECTIVE:
      The aim of this study was to investigate the efficacy of lidocaine, at different
      doses and schedules, on propofol injection pain. METHODS: In this open-label
      study, conducted at the Department of Anaesthesiology, Erciyes University Gevher
      Nesibe Hospital (Kayseri, Turkey), patients with American Society of
      Anesthesiologists Patient Acuity Classification I-II (ASA I-II) (ie, patients
      with absent [I] or mild [II] underlying systemic disease) aged 18 to 60 years
      undergoing various types of surgery were eligible. Patients were randomized to 1
      of 4 treatment groups: group 1 received propofol; group 2, a combination of
      propofol plus lidocaine 10 mg; group 3, lidocaine 10 mg 30 seconds before
      propofol administration; and group 4, lidocaine 1 mg/kg 30 seconds before
      propofol administration (all drugs were administered intravenously). After
      cessation of the standard replacement fluid infusion (isotonic saline), propofol
      was given at a rate of 2 mL every 5 seconds until a dose of 2 mg/kg was reached.
      The patients were asked to rate their pain according to the following scale: 0 =
      none, 1 = mild, 2 = moderate, and 3 = severe. RESULTS: A total of 120 patients
      (61 men, 59 women; mean [SD] age, 38.7 [8.9] years) were enrolled in the study (n
      = 30 patients in each group). The incidence of injection pain in groups 2 and 4
      was significantly lower than that in groups 1 and 3 (all P<0.05), but no
      significant difference in the incidence of pain was found between groups 1 and 3.
      The incidence of pain in group 2 was significantly lower than that in group 4
      (P<0.05). CONCLUSIONS: In this study population, the addition of 10 mg of
      lidocaine to propofol 2 mg/kg, or the administration of 1 mg/kg of lidocaine 30
      seconds before the administration of propofol 2 mg/kg, effectively decreased pain
      caused by propofol injection. Furthermore, a lower dose of lidocaine could be
      used. Based on our results, we suggest mixing propofol with 10 mg of lidocaine to
      decrease pain due to propofol injection during anesthesia induction.

PMID- 24944381
TI  - Current therapeutic research.

PMID- 24944380
TI  - Effects of formoterol inhaled dry powder on exercise performance in chronic
      obstructive pulmonary disease: a single-center, randomized, double-blind, placebo
      controlled, crossover study.
AB  - BACKGROUND: Inhaled bronchodilators commonly are used to reduce the work of
      breathing in patients with chronic obstructive pulmonary disease (COPD). The
      effects of bronchodilators are assessed in terms of symptom relief and/or
      improvements in spirometric indices. However, disability in COPD patients also is
      related to determinants such as exercise tolerance, which cannot be predicted on
      the basis of respiratory function. The effect of bronchodilators, such as inhaled
      beta2-agonists, on exercise performance of COPD patients needs to be tested.
      OBJECTIVE: This study investigated the effects of formoterol inhaled dry powder
      on exercise performance assessed using the shuttle walking test (SWT) in patients
      with mild to moderate COPD. METHODS: Patients having COPD with mild to moderate
      airway obstruction performed a pulmonary function test and an SWT before and
      after inhalation, on 2 consecutive days, of formoterol 12 MUg or placebo, given
      by dry powder inhaler, according to a double-blind, placebo-controlled, crossover
      study design. Breathlessness was measured using the Borg scale (BS) and a visual
      analog scale at baseline and after an SWT. RESULTS: Twenty patients (15 men, 5
      women; mean [SD] age, 65.95 [8.32] years) were included in the study. Forced
      expiratory volume in 1 second (FEV1) (P = 0.009), forced mid-expiratory flow
      (FEF25-75) (P = 0.011), and SWT (P = 0.005) improved significantly more with
      formoterol than placebo. Breathlessness decreased with formoterol, but the
      difference compared with placebo was statistically significant only when measured
      using the BS (P = 0.023). In the pooled placebo and formoterol tests, changes in
      the SWT were unrelated to changes in FEV1 (r = 0.18) and in FEF25-75 (r = 0.31).
      CONCLUSIONS: The results of this study showed that formoterol inhaled dry powder
      significantly improved exercise performance in patients with COPD and that this
      effect was at least partially independent of achieved bronchodilation. A larger
      cohort of patients should be studied and a more comprehensive protocol performed
      to verify whether the increase in exercise tolerance after administration of
      formoterol is related to a decrease in expiratory flow limitation during exercise
      and/or to systemic effects of the drug. Another issue to be clarified is whether
      the improvement in exercise capacity can significantly decrease disability in
      patients with severe COPD.

PMID- 24944382
TI  - Analgesia with ibuprofen arginate versus conventional ibuprofen for patients with
      dysmenorrhea: a crossover trial.
AB  - BACKGROUND: Dysmenorrhea produces painful abdominal cramps that can disrupt the
      personal lives and productivity of women. OBJECTIVE: The aim of this study was to
      compare the analgesic efficacy, including onset and duration of pain relief, peak
      effect, and total effect, and tolerability of ibuprofen arginate with those of
      conventional ibuprofen in patients with moderate to severe pain associated with
      primary dysmenorrhea. METHODS: Patients were administered a single dose of
      ibuprofen arginate (200 or 400 mg), conventional ibuprofen (200 or 400 mg), or
      placebo during each of 5 menstrual cycles in a single-center, double-blind,
      randomized, double-dummy, 5-cycle, crossover study. Patients recorded their pain
      intensity and pain relief at regularly scheduled intervals (10, 20, 30, 40, 50,
      60, and 90 minutes and 2, 3, 4, 5, and 6 hours) after taking the study
      medication, and all study observations were recorded in a patient diary. Pain
      intensity was rated using the following 4-point categoric rating scale: 0 = none,
      1 = mild, 2 = moderate, and 3 = severe. Pain relief was rated on a 5-point scale
      as 0 = none, 1 = a little, 2 = some, 3 = a lot, and 4 = complete relief.
      Tolerability of ibuprofen arginate was based on a comparison of the incidence of
      spontaneously reported adverse events in each of the treatment groups. RESULTS:
      One hundred four patients entered the study. Of these, 81.7% were white; the mean
      (SD) age was 27.5 (5.0) years. A total of 65.4% of patients reported moderate
      pain from dysmenorrhea, and the remaining 34.6% reported severe pain; 20.2% of
      patients did not complete the study. The median time to achieve meaningful pain
      relief was ~30 minutes faster with ibuprofen arginate 400 mg than with either
      dose of conventional ibuprofen. Tolerability was similar across all treatments.
      CONCLUSIONS: In this study population of patients experiencing acute pain as a
      result of primary dysmenorrhea, ibuprofen arginate was associated with effective,
      tolerable analgesia and a more rapid onset of action than conventional ibuprofen.
      The faster onset of analgesia may have a role in clinical practice in treating
      women with dysmenorrhea. A faster onset of action may be important to women whose
      personal relationships, productivity, or ability to sleep is being adversely
      affected by pain.

PMID- 24944383
TI  - A six-month, multicenter, open-label, noncomparative, prospective, observational
      study of the efficacy and tolerability of atorvastatin in the primary care
      setting(estudio del control de las hiperlipidemiasen atencion primaria): the
      cheap study.
AB  - BACKGROUND: A close relationship exists between high levels of total cholesterol
      (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of
      high-density lipoprotein cholesterol (HDL-C), which is associated with an
      increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence
      shows that atorvastatin produces significantly greater reductions in LDL-C and TC
      than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the
      results achieved in clinical studies could be different from those found in
      general clinical practice, where patient follow-up is less thorough and poorer
      compliance may reduce the effectiveness of the lipid-lowering therapy. OBJECTIVE:
      The aim of this study was to assess the effectiveness of atorvastatin in
      achieving the LDL-C levels recommended by several Spanish scientific societies,
      as well as its tolerability in standard clinical use. METHODS: This 6-month, open
      label, noncomparative, prospective, observational study was conducted in 1351
      primary care centers in Spain. All patients were aged 18 to 80 years and had
      primary hypercholesterolemia (TC >200 mg/dL and triglycerides [TG] <lt;200 mg/dL)
      or combined hyperlipidemia (TC >200 mg/dL and fasting TG 200-400 mg/dL). All
      patients also had LDL-C levels higher than those established by the Spanish
      Society of Arteriosclerosis (Sociedad Espanola de Arteriosclerosis [SEA])
      according to baseline cardiovascular risk and previous use of lipid-lowering
      therapy (for patients with low, moderate, or high cardiovascular risk, the
      recommended LDL-C goals are <=175 mg/dL, <=155 mg/dL, and <=135 mg/dL,
      respectively; for patients with CVD, the LDL-C goal is <=100 mg/dL). None of the
      patients had creatine kinase activity >=540 U/L or alanine aminotransferase (ALT)
      or aspartate aminotransferase (AST) levels >=60 U/L. Study visits occurred at
      months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d
      for 2 months. The dosage was then doubled to 20 mg/d in patients who did not
      achieve the SEA LDL-C goal and also in those patients whose primary care
      physicians (PCPs) deemed this higher dosage necessary; this dosage was continued
      for at least 4 additional months, to complete at least a 6-month course of
      treatment. The percentage of patients who achieved their goals was used to
      measure atorvastatin effectiveness. Percentages of change in LDL-C, TC, TG, and
      HDL-C from baseline to the final study visit also were used as measures of
      effectiveness. The incidence of adverse events (AEs) per 10,000 patient-months
      was used for the primary tolerability analysis. A secondary tolerability analysis
      was performed in all patients treated with atorvastatin who had some recorded
      follow-up, regardless of whether the patient met inclusion criteria. Information
      was obtained from data recorded in the case-report forms. RESULTS: A total of
      5317 outpatients (2715 women, 2598 men, 4 sex unknown; mean [SD] age, 58.7 [10.5]
      years) were enrolled. Among patients receiving known dosages of atorvastatin,
      1580 of 4033 (39.2%) and 2378 of 3585 (66.3%) patients met the SEA LDL-C goal
      after 2 and 6 months of therapy, respectively (P<lt;0.001 for 2 months vs 6
      months). Among the patients with low and moderate cardiovascular risk, 85.8%
      achieved the SEA LDL-C goal compared with 64.4% of high-risk patients
      (P<lt;0.001). Mean LDL-C decreased by 36.2%. Mean reductions in TC and TG levels
      were 26.9% and 19.2%, respectively. Mean HDL-C increased 17.0%. One hundred forty
      eight patients (2.9%) experienced at least 1 AE and 25 (0.5%) had serious AEs.
      Eighty-nine patients had 134 AEs considered treatment related. Two of the serious
      AEs (phlebitis and a severe increase in ALT and AST activity) were considered
      treatment related. A total of 98.5% and 97.2% of PCPs and patients, respectively,
      reported excellent or good tolerability with atorvastatin. CONCLUSIONS: In this
      study population, the use of atorvastatin in the primary care setting was
      associated with high achievement rates of the SEA LDL-C goals and with a
      substantial decrease in TG levels. In addition, a considerable increase in HDL-C
      levels occurred. Tolerability with atorvastatin was reported to be excellent or
      good by most of the patients and PCPs. The incidence of serious AEs was minimal,
      as reported by both patients and PCPs.

PMID- 24944384
TI  - Effects of trapidil on intestinal mucosal barrier function and bacterial
      translocation after intestinal ischemia and reperfusion in an experimental rat
      model.
AB  - BACKGROUND: Intestinal ischemia and reperfusion may be the primary triggers of
      mucosal barrier impairment, cytokine expression, and bacterial translocation
      (BT). Trapidil is a phosphodiesterase and platelet-derived growth factor
      inhibitor that reduces lipid peroxidation and inhibits the production of
      cytokines. OBJECTIVE: The goal of this study was to assess whether trapidil might
      protect the intestinal epithelial barrier by inhibiting lipid peroxidation and
      proinflammatory cytokines by testing the effect of trapidil on intestinal barrier
      function in an experimental ischemia/reperfusion (I/R) rat model. METHODS:
      Trapidil was used in a rat model of intestinal barrier dysfunction caused by
      intestinal ischemia for 40 minutes followed by reperfusion for 12 hours. To do
      this, the rats were randomized to 1 of 4 treatment groups, as follows: (1) sham
      surgery and saline administration (1 mL IV) (Sham group); (2) sham surgery and
      trapidil administration (8 mg/kg IV) (Sham+T group); (3) I/R and saline
      administration (1 mL IV) (I/R group); and (4) I/R and trapidil administration (8
      mg/kg IV) (I/R+T group). Intestinal barrier function was assessed by
      histopathologic examination, blood malondialdehyde (MDA) level, and BT. RESULTS:
      The I/R+T group showed significantly less incidence of BT compared with the I/R
      group in the liver and reduced median colony count of translocated bacteria in
      mesenteric lymph nodes, liver, spleen, and peritoneum compared with the I/R
      group. Furthermore, the mean blood MDA level demonstrated that lipid peroxidation
      was significantly decreased in the I/R+T group compared with the I/R group.
      Histopathologic findings revealed that trapidil administration before reperfusion
      preserved intestinal mucosal integrity and inhibited the infiltration of
      inflammatory cells into the intestines. CONCLUSIONS: In this experimental study,
      a correlation seemed to exist between intestinal barrier dysfunction and BT.
      Intestinal barrier dysfunction may allow a large amount of bacteria to pass from
      the gut to distant organs. Trapidil treatment may inhibit BT by preserving
      intestinal barrier by inhibiting thromboxane A2, lipid peroxidation,
      proinflammatory cytokines, and stimulated prostacyclin. Future dose- and time
      dependent studies will be helpful in revealing the effects of trapidil on BT.

PMID- 24944385
TI  - Drug-induced cardiotoxicity due to aminophylline treatment: a case report.
AB  - BACKGROUND: Aminophylline, a theophylline compound that contains ethylenediamine,
      has untoward side effects on many organ systems. OBJECTIVE: The goal of this case
      report was to illustrate the occurrence of acute adverse events (ie, chest
      discomfort and myocardial enzyme elevation) that may be associated with
      aminophylline treatment. METHODS: To uncover previous studies/reports on this
      subject, a literature search (1950-2003) was conducted on MEDLINE, UpToDate, and
      Doctor's Guide, using the search terms aminophylline toxicity, theophylline
      toxokinetics, pharmacotoxic myocardial injury, hypersensitivity myocarditis, and
      diagnosis of myocardial infarction with biomarkers of cardiac injury. A 76-year
      old, obese, female patient was admitted to University Hospital (Rion, Greece) for
      an acute exacerbation of chronic bronchitis. Beginning on day 0 of
      hospitalization, the patient was treated with aminophylline 750 mg IV, given in a
      24hour constant infusion, for persistent wheezing. We monitored the patient's
      condition using electrocardiography, echocardiography, and blood chemistry
      analysis. RESULTS: While undergoing aminophylline treatment, the patient
      developed vague chest discomfort and myocardial enzyme elevation due to
      aminophylline-induced cardiotoxicity. Mild wheezing was still present on physical
      examination on day 2 of hospitalization. The serum creatine kinase (CK) level was
      slightly increased. On day 6 of hospitalization, the patient's symptoms worsened,
      with mild epigastric discomfort, tachycardia, fatigue, and tightness in the
      chest. Blood gas analysis revealed mild hypoxia and hypocapnia. Pulmonary
      perfusion scan showed a low risk for pulmonary thromboembolism, as indicated by
      the absence of segmental perfusion defects. Blood chemistry analysis showed
      increased serum CK (*2.5) and CK isoenzyme (CK-MB) fraction (*8.6) levels.
      Echocardiography on day 7 showed a slight hypertrophy of the septum, with normal
      dimensions of the ventricles and a 70% ejection fraction. Aminophylline treatment
      was permanently discontinued, and the patient's signs and symptoms promptly
      improved. CONCLUSIONS: In the case presented here, the exclusion of usual causes
      of increased serum CK and CK-MB fraction levels, together with the increased
      serum aminophylline concentration and, most importantly, the rapid alleviation of
      symptoms and normalization of myocardial enzymes in absolute temporal
      relationship to the discontinuation of the drug, suggested that aminophylline
      treatment might be associated with elevated levels of myocardial enzymes. (Curr
      Ther Res Clin Exp. 2003;64:379-386).

PMID- 24944386
TI  - Sensitivity of polymerase chain reaction to determine chlamydia trachomatis
      eradication rate with levofloxacin therapy in patients with chlamydial
      cervicitis.
AB  - BACKGROUND: For the treatment of chlamydial cervicitis, a 7- to 14-day regimen
      with appropriate antibacterial agents (eg, macrolides, tetracycline,
      fluoroquinolones) has been recommended. Many clinicians in Japan have determined
      the eradication rate of cervical Chlamydia trachomatis by polymerase chain
      reaction (PCR) prior to 3 weeks after treatment because patients' second visit
      rate has been low. OBJECTIVE: The aim of this study was to assess the sensitivity
      of PCR to detect C trachomatis at various time points after antibacterial
      treatment. METHODS: The presence of C trachomatis was determined by PCR on days
      8, 15, and 22 after the end of treatment. All patients received a 7-day course of
      levofloxacin 300 mg/d. RESULTS: The eradication rates of cervical C trachomatis
      were 90.0%, 97.5%, and 100.0% on days 8, 15, and 22 after treatment,
      respectively. CONCLUSION: Based on data from this study, the appropriate method
      and time to assess the therapeutic efficacy for chlamydial infection is PCR at 3
      weeks after treatment.

PMID- 24944387
TI  - Current therapeutic research.

PMID- 24944389
TI  - Comparison of candesartan and felodipine alone and combined in the treatment of
      hypertension: a single-center, double-blind, randomized, crossover trial.
AB  - BACKGROUND: In the past decade, many studies have indicated that the combination
      of low doses of different classes of antihypertensive agents may be more
      efficacious than monotherapy while minimizing the likelihood of dose-dependent
      adverse effects (AEs). OBJECTIVE: The aim of this study was to determine whether
      combination therapy with lower doses of candesartan and a calcium antagonist,
      felodipine, would be more effective and tolerable in controlling mild to moderate
      hypertension compared with either drug used alone. METHODS: In this 18-week,
      single-center, double-blind, crossover study, patients with mild to moderate
      essential hypertension were randomized to 1 of 2 treatment groups after a 2-week
      placebo washout period. Patients in group 1 received candesartan 16 mg once daily
      and patients in group 2 received felodipine 5 mg once daily, for 6 weeks. All
      patients then received half-dose combination therapy (candesartan 8 mg plus
      felodipine 2.5 mg, once daily) for 6 weeks. Finally, patients received 6 weeks of
      monotherapy with the alternate medication (group 1 received felodipine 5 mg once
      daily and group 2 received candesartan 16 mg once daily). RESULTS: Thirty
      patients (18 men, 12 women; mean [SD] age, 54.0 [4.9] years; range, 39-62 years)
      were included in the study. During both monotherapy periods, candesartan and
      felodipine significantly reduced blood pressure (BP) (both P<0.001). BP further
      decreased with combination therapy (P<0.001 in both groups). Overall, 90.0%
      (27/30) of the patients achieved the target BP at the end of combination therapy.
      The incidence of AEs was similar with combination therapy compared with either
      monotherapy. CONCLUSIONS: In this study population, candesartan and felodipine
      had additive effects when used in combination, even at low doses, in the
      treatment of hypertension. Therefore, the combination of candesartan and
      felodipine is an effective alternative to that of candesartan and
      hydrochlorothiazide.

PMID- 24944390
TI  - Effects of travoprost eye drops on intraocular pressure and pulsatile ocular
      blood flow: a 180-day, randomized, double-masked comparison with latanoprost eye
      drops in patients with open-angle glaucoma.
AB  - BACKGROUND: Because of the increasing realization of the importance of optic
      nerve head perfusion in the pathogenesis of glaucoma, the influence of new
      antiglaucomatous drugs on ocular hemodynamic properties should be investigated.
      OBJECTIVE: The aim of this study was to compare the effects of 2 prostaglandin
      analogues, travoprost eye drops and latanoprost eye drops, on intraocular
      pressure (IOP) and pulsatile ocular blood flow (pOBF) in patients with primary
      open-angle glaucoma (POAG). METHODS: Previously untreated patients aged 40 to 60
      years with POAG and normal brachial blood pressure (BBP), heart rate, body mass
      index, and hemorheologic findings were eligible for this randomized, double
      masked study. Two drops of travoprost (group T) or latanoprost (group L) were
      self-administered in both eyes at 9:00 pm. In all patients, IOP, pOBF, BBP, and
      heart rate were measured at baseline and on days 15, 30, 60, 90, and 180 of
      treatment. RESULTS: Twenty-five consecutive patients with POAG were enrolled in
      this study conducted at the Glaucoma Research Center of the Department of
      Ophthalmology, Bari University, Policlinico di Bari (Bari, Italy). Of these, 7
      were withdrawn because they did not return for the second appointment, leaving 18
      patients (11 men, 7 women; mean [SD] age, 51.9 [5.5] years) to complete the
      study. In both groups, mean IOP values were significantly reduced at all time
      points compared with baseline (all P<0.01). Mean pOBF values increased ~50% from
      baseline following treatment with either travoprost or latanoprost by day 15,
      were maintained at that level for 60 days, and then gradually decreased (group T:
      P = NS, NS, <0.01, <0.05, and <0.05 at days 15, 30, 60, 90, and 180,
      respectively, vs baseline; group L: P<0.01 at all time points vs baseline). All
      other parameters remained constant throughout the study. An early inverse
      correlation between IOP and pOBF was noted in group T but not in group L. No
      significant differences were found between groups in IOP or pOBF at any time
      point. CONCLUSIONS: In this study population, pOBF was increased with travoprost
      and latanoprost in the short term, but this effect was kept constant only with
      travoprost. IOP was reduced with both drugs after short-term therapy, and this
      reduction was maintained in both groups. Travoprost may represent another option
      for the medical treatment of POAG.

PMID- 24944391
TI  - A new high-absorption-rate Paracetamol 500-mg formulation: a comparative
      bioavailability study in healthy volunteers.
AB  - BACKGROUND: Paracetamol is often the analgesic or antipyretic of choice,
      especially for patients for whom salicylates or other nonsteroidal anti
      inflammatory drugs are contraindicated. OBJECTIVE: The aim of this study was to
      compare the absorption rate of a new tablet formulation of paracetamol (500 mg)
      with a reference formulation of paracetamol at the same dose. METHODS: This was a
      single-center, Phase I, open-label, randomized, 2-period, crossover, single-dose,
      comparative bioavailability clinical trial. During both study periods, healthy
      volunteers were given a single oral dose of a more hydrophilic test formulation
      of paracetamol, or a reference formulation. Fifteen plasma samples were obtained
      to determine paracetamol concentrations and to calculate kinetic parameters.
      RESULTS: The study participants comprised 24 healthy volunteers (12 men, 12
      women; mean [SD] age, 22.8 [1.5] years). The pharmacokinetic parameters
      calculated for the test versus the reference formulation were as follows: median
      time to maximum concentration (Tmax), 0.42 versus 0.75 hour; mean (SD) maximum
      plasma drug concentration (Cmax), 9.85 (2.40) MUg/mL versus 8.33 (2.22) MUg/mL;
      and mean (SD) area under the plasma concentration-time curve from time 0 to
      infinity (AUC0-infinity), 30.16 (8.87) MUg.h/mL versus 28.49 (8.57) MUg . h/mL.
      The 90% CIs of the ratios were as follows: base e logarithm (Ln)-transformed
      Cmax, 105.08% to 137.59%; Ln-AUC0-infinity, 102.02% to 110.43%; and the
      difference in Tmax, -0.375 to -0.085 hours. CONCLUSIONS: The speed of release and
      absorption was statistically significantly higher with the test formulation
      compared with the reference one (evaluated using Tmax, Cmax, and Cmax/AUC
      parameters). This speed is especially important for a rapid analgesic or
      antipyretic effect.

PMID- 24944392
TI  - Comparison of five-day Helicobacter pylori eradication regimens: rabeprazole
      based and omeprazole-based regimens with and without omeprazole pretreatment.
AB  - BACKGROUND: The onset of antisecretory activity of rabeprazole is faster than
      that of omeprazole. OBJECTIVE: This study was performed to compare the efficacy
      of short-term rabeprazole-based triple therapy with that of omeprazole-based
      triple therapy and to determine the influence of omeprazole pretreatment in
      omeprazole-based short-term triple therapy. METHODS: This was a 2-center, open
      label, prospective, randomized study. Patients who tested positive for
      Helicobacter (formerly Campylobacter) pylori were randomized to one of three 5
      day regimens: (1) rabeprazole 20 mg BID, amoxicillin 500 mg TID, and
      clarithromycin 400 mg BID (RAC group); (2) omeprazole 20 mg BID, amoxicillin 500
      mg TID, and clarithromycin 400 mg BID without omeprazole pretreatment (OAC1
      group); and (3) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin
      400 mg BID with 5 days of omeprazole pretreatment 20 mg BID (OAC2 group).
      Eradication was assessed by (13)C-urea breath test and rapid urease test ~1 month
      after completion of treatment. All patients who entered this study were included
      in the intent-to-treat (ITT) analysis, patients who completed the study were
      included in the per-protocol (PP) analysis, and patients who did not undergo the
      (13)C-urea breath test and rapid urease test were included in the all-patients
      treated (APT) analysis. RESULTS: A total of 120 patients (86 men, 34 women; mean
      [SD] age, 55.8 [14.3] years; range, 19-86 years) were assigned to the RAC, OAC1,
      or OAC2 group (40 patients in each group). ITT, PP, and APT eradication rates in
      the RAC group were 90%, 92%, and 90%, respectively; in the OAC1 group, 75%, 83%,
      and 75%; and in the OAC2 group, 85%, 90%, and 87%. These eradication rates were
      not significantly different between groups. CONCLUSIONS: Eradication rates did
      not differ significantly between the three 5-day proton pump inhibitor-based
      triple therapies in this study population. However, 5-day rabeprazole-based
      triple therapy tends to be more effective than 5-day omeprazole-based triple
      therapy in the eradication of H pylori, and treatment with omeprazole before
      eradication therapy may improve the eradication rates of 5-day omeprazole-based
      therapy.

PMID- 24944393
TI  - Effects of the fixed combination of manidipine plus delapril in the treatment of
      hypertension inadequately controlled by monotherapy with either component: a
      phase III, multicenter, open-label, clinical trial.
AB  - BACKGROUND: Failure to achieve good blood pressure (BP) control is probably the
      most important reason for high rates of morbidity and mortality in patients with
      hypertension. Combination therapy has been shown to increase the percentage of
      patients in whom BP control is achieved. One combination is a calcium channel
      blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I). OBJECTIVE:
      The aim of this study was to assess the effects of the fixed combination of the
      CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients
      already given monotherapy with either component but with poor results (ie,
      insufficient BP control or adverse events [AEs]). METHODS: In this Phase III,
      multicenter, open-label, clinical trial, patients with mild to moderate
      hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose
      diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg
      once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced
      AEs with delapril 30 mg BID. In both groups, patients aged <65 years were to be
      treated with a fixed combination of manidipine 10 mg plus delapril 30 mg once
      daily for 12 weeks, whereas patients aged >=65 years were to be treated with
      manidipine 5 mg plus delapril 15 mg once daily for 2 weeks and then manidipine 10
      mg plus delapril 30 mg once daily for 10 weeks. Patients were assessed at
      baseline and at 2, 4, 8, and 12 weeks of treatment. At each visit, systolic blood
      pressure (SBP), DBP, and heart rate were measured 24 hours after dosing, and AEs
      were recorded. RESULTS: Group 1 included 154 patients (80 men, 74 women; mean
      [SD] age, 55 [6] years); group 2 included 158 patients (79 men, 79 women; mean
      [SD] age, 56 [5] years). Mean BP decreased significantly in both groups (P<0.01).
      Compared with baseline values, mean SBP/DBP decreased 16.2 (3.8)/10.1 (1.9) mm Hg
      in group 1 and 15.8 (3.1)/11.0 (1.5) mm Hg in group 2 at the last visit. The
      success rate-rate of normalized DBP (<=90 mm Hg) and responder rate (DBP
      reduction >=10 mm Hg)-was 79% in group 1 and 82% in group 2. The rates of
      treatment-related AEs were 11% in group 1 and 8% in group 2. In group 1, heart
      rate significantly increased from baseline only at 2 weeks (P<0.05); in group 2,
      at each visit (P<0.05) except at week 12. However, none of these differences were
      clinically significant. CONCLUSION: In this study population of patients whose BP
      was not adequately controlled by monotherapy, the fixed combination of manidipine
      10 mg plus delapril 30 mg, once daily, was effective and well tolerated.

PMID- 24944394
TI  - Effects of fenofibrate on albuminuria in patients with hypertriglyceridemia
      and/or hyperuricemia: a multicenter, randomized, double-blind, placebo
      controlled, crossover study.
AB  - BACKGROUND: A slight increase in albuminuria (urinary albumin excretion [UAE]
      >=30 mg/d) is associated with hypertension, type 2 diabetes mellitus,
      dyslipidemia (high triglyceride [TG] and low high-density lipoprotein cholesterol
      [HDL-C] concentrations), and hyperuricemia. Although antihypertensive and
      antidiabetic therapies have been reported to reduce UAE, an association between
      improvement in dyslipidemia and/or hyperuricemia and a reduction in UAE has not
      been reported. OBJECTIVE: The aim of this study was to investigate the efficacy
      and tolerability of fenofibrate on albuminuria in patients with
      hypertriglyceridemia and/or hyperuricemia. METHODS: Patients with
      hypertriglyceridemia and/or hyperuricemia were recruited from general clinics and
      lipid clinics in Japan; they received fenofibrate (300 mg once daily) in this
      randomized, double-blind, placebo-controlled, crossover study. Patients in group
      A received fenofibrate for 8 weeks followed by placebo for an additional 8 weeks,
      whereas those in group B received placebo for 8 weeks followed by fenofibrate for
      8 additional weeks. UAE was measured at baseline and at the end of each 8-week
      period. Blood tests were performed at baseline and every 4 weeks until study end.
      Each physician who participated in the study was to record adverse events at each
      study visit. RESULTS: A total of 43 patients entered this study (38 men, 5 women;
      mean [SE] age, 57.1 [1.4] years; mean [SE] body mass index, 24.3 [0.4] kg/m(2)).
      Twenty-one patients (18 men, 3 women) were randomly assigned to group A and 22
      (20 men, 2 women) to group B. In group A, serum TG (P<0.001) and apolipoprotein
      (apo) C2, C3, and E (all P<0.01) concentrations decreased significantly with
      fenofibrate, and HDL-C and apo A1 and A2 increased significantly (all P<0.001).
      All of these parameters returned to near-baseline levels after placebo
      administration. In group B, serum TG, HDL-C, or apo A1, A2, B, C2, C3, and E
      concentrations did not change significantly with placebo, but TG (P<0.01), apo C3
      (P<0.05), and apo E (P<0.05) were significantly decreased with fenofibrate. In
      addition, HDL-C (P<0.05), apo A1 (P<0.001), and apo A2 (P<0.01) were
      significantly increased with fenofibrate. Serum concentrations of TG (group A,
      P<0.001; group B, P<0.001); apo C2 (group A, P<0.01), C3 (group A, P<0.01; group
      B, P<0.05), and E (group A, P<0.01; group B, P<0.05); and uric acid (group A,
      P<0.001; group B, P<0.01) were significantly decreased with fenofibrate compared
      with placebo. HDL-C and apo A1 and A2 were significantly increased with
      fenofibrate compared with placebo (all P<0.001 in both groups). Fenofibrate
      treatment was associated with significant reductions in UAE (group A, P<0.05;
      group B, P<0.01). Spearman rank correlation analysis showed that changes in UAE
      were associated with changes in apo C2 (rho = 0.43; P = 0.02) and apo C3 (rho =
      0.49; P = 0.01) concentrations. Multiple regression analysis revealed that a
      decrease in apo C3 concentration was independently and significantly associated
      with reductions in albuminuria (rho = 0.48; P = 0.01). At the end of the study,
      neither drug-related nor clinical adverse events were evident in any of the
      patients, except for an increase in serum creatinine concentration above the
      upper limit of normal (1.40 mg/dL) in 3 patients (14.3%) in group A and 1 patient
      (4.5%) in group B. CONCLUSIONS: In our study population of patients with
      hypertriglyceridemia and/or hyperuricemia, fenofibrate-induced ameliorations of
      impaired TG-rich lipoprotein metabolism were associated with reductions in
      albuminuria.

PMID- 24944395
TI  - Body weight loss with phentermine alone versus phentermine and fenfluramine with
      very-low-calorie diet in an outpatient obesity management program: a
      retrospective study.
AB  - BACKGROUND: Obesity, which is epidemic in the United States, is associated with
      increased morbidity and mortality. The combination of diet, exercise, and a
      behavior-modification program often does not result in ideal body weight.
      OBJECTIVE: The aim of this study was to determine the efficacy of phentermine
      (Phen) alone compared with phentermine plus fenfluramine (Phen-Fen), when used in
      combination with a very-low-calorie diet (VLCD) for weight loss in an outpatient
      obesity center. METHODS: We analyzed data collected at the UCLA outpatient
      University Obesity Center between 1993 and 1999. Data for patients who attended
      the center for at least 12 weeks and at least 4 visits, who were taking Phen or
      Phen-Fen, and whose body mass index (BMI) was >=30 kg/m(2) were included in this
      retrospective study. RESULTS: During the study period, 3200 visits were recorded.
      Of 1133 potential participants, 446 patients were included in the analysis (309
      women, 137 men; mean [SD] age, 46.7 [11.4] years; mean [SEM] body weight, 109.6
      [26.7] kg; mean [SEM] BMI, 38.0 [7.6] kg/m(2)). Of these, 128 women and 60 men
      (mean [SEM] body weight at baseline, 103.4 [24.0] kg and 124.9 [28.2] kg,
      respectively) received Phen alone; 181 women and 77 men (mean [SEM] body weight
      at baseline, 102.5 [21.4] kg and 124.9 [30.2] kg, respectively) received Phen
      Fen. No statistically significant differences were found between the Phen and
      Phen-Fen groups in mean age, body weight, or BMI for women or men at baseline. No
      significant differences in the time of weight loss were found when a VLCD was
      used with Phen alone compared with the Phen-Fen combination for either sex even
      at 12 weeks. For women, the mean total body weight loss was 7.4% in the Phen
      group and 8.7% in the Phen-Fen group, but these differences were not significant.
      For men, the mean total body weight loss was 7.8% in the Phen group and 8.2% in
      the Phen-Fen group, but these differences were not significant. No significant
      differences in BMI, severe adverse events, or dropout rate were found between the
      2 treatment groups for men or women. CONCLUSIONS: This outpatient study did not
      detect any significant difference between adjunctive uses of Phen compared with
      Phen-Fen pharmacotherapy when used with VLCD over 12 weeks. Phen can be used to
      achieve significant weight loss when combined with VLCD. The tolerability and
      positive physical response further suggest that Phen is a valuable medication for
      obesity management in the outpatient setting.

PMID- 24944397
TI  - Combination therapy for chronic invasive rhinocerebral aspergillosis in a
      clinically immunocompetent patient.
AB  - BACKGROUND: Adequate therapy for chronic invasive rhinocerebral aspergillosis in
      immunocompetent patients is controversial. The incidence of the disease is high
      in the Sudan and the Middle East. Misinterpretation of diagnostic criteria,
      failure to verify tissue invasion of fungi, and a lack of understanding of the
      pathophysiology of various forms of fungal rhinosinusitis lead to controversies
      in nomenclature, diagnosis, and therapy. OBJECTIVE: The aim of this report was to
      detail the clinical presentation and the endoscopic and imaging study findings of
      a patient with invasive Aspergillus rhinosinusitis with endocranial and orbital
      extension. This patient was treated with surgical debridement and a combination
      of antifungal drugs and immunomodulatory therapy. METHODS: Endoscopic debridement
      and high-dose liposomal amphotericin B, in combination with flucytosine and
      immunomodulators, were used to treat this patient. RESULTS: After treatment, the
      patient experienced 3 years of disease-free follow-up. CONCLUSION: Surgical
      debridement and high-dose systemic combined antifungal therapy with
      immunomodulatory drugs produced an excellent long-term result for this apparently
      immunocompetent patient with extensive invasive fungal rhinosinusitis with
      cerebral and orbital involvement.

PMID- 24944396
TI  - Effect of the radiographic contrast material iopamidol on hemostasis: an
      observational study in thirty cardiac patients.
AB  - BACKGROUND: In vitro studies have shown that nonionic radiographic contrast
      material may induce the generation of thrombin in blood, whereas ionic contrast
      agents, such as iohexol, do not. However, knowledge of the effects of contrast
      material on coagulation and fibrinolytic systems in vivo is limited. OBJECTIVE:
      This study was designed to assess the effects of the nonionic radiographic
      contrast material iopamidol on hemostasis in patients undergoing coronary
      angiography or cardiac catheterization. METHODS: Patients aged >=18 years with
      chest pain and/or dyspnea who underwent coronary angiography or cardiac
      catheterization with intra-arterial contrast material were assessed for
      hemostasis. Blood samples were drawn before and 3 minutes after injection of
      iopamidol. Complete blood count and coagulation profile (bleeding time, clotting
      time, clot retraction time, euglobulin lysis time [ELT], prothrombin and partial
      thromboplastin times, coagulation factor I [CFI] level, and platelet factor 3 [PF
      3] availability) were assessed. The natural coagulation inhibitors protein C,
      protein S, and antithrombin III (AT-III) also were measured. RESULTS: Thirty
      patients (7 males, 23 females; mean [SD] age, 51.3 [20.2] years; range, 17-79
      years) were included in this single-center study. All hematologic variables
      (hemoglobin, white blood cell count, and platelet count) decreased significantly
      (P<0.001, P<0.001, and P<0.05, respectively) after administration of iopamidol
      but remained within normal limits. Mean levels of protein C, protein S, and AT
      III did not change significantly after administration of iopamidol. Bleeding time
      was not changed significantly, and PF-3 availability was prolonged in both
      groups, but the changes were not statistically significant. CONCLUSIONS: In this
      study population, although hemostasis remained grossly intact after injection of
      nonionic contrast material, the coagulation system may have been affected by the
      accelerated consumption of CFI and platelets. The affected variables were
      platelets, clot retraction time, ELT, and natural coagulation inhibitors (protein
      C, protein S, and AT-III). Although the natural coagulation inhibitors remained
      within the normal range, the correlations were found significant. These changes
      in hemostasis affected the vascular phase. If the vascular compartment,
      especially the endothelium, remained intact, the infusion of nonionic agents in
      low concentrations might be safe for angiography and other procedures; however,
      more studies are needed.

PMID- 24944398
TI  - High-powered rifles versus shotguns.

PMID- 24944399
TI  - Comparison of beraprost and ticlopidine in Chinese patients with chronic
      peripheral arterial occlusion: a multicenter, single-blind, randomized,
      controlled study.
AB  - BACKGROUND: Chronic peripheral arterial occlusion (CPAO) is a progressive disease
      that is associated with a variety of symptoms, the 4 most common being a
      sensation of coolness in the limbs, intermittent claudication (in which pain
      occurs on walking), limb pain (which occurs spontaneously at rest), and ischemic
      leg ulcers. Beraprost sodium is an oral prostaglandin I2 analogue that may
      ameliorate these symptoms. OBJECTIVE: The aim of this study was to compare the
      efficacy and tolerability of beraprost sodium and ticlopidine hydrochloride in
      the treatment of patients with CPAO in China. METHODS: In this multicenter,
      single-blind, controlled study, patients with CPAO were randomly assigned to
      receive beraprost 120-MUg tablet TID or ticlopidine 500-mg tablet BID, both
      administered orally. The clinical efficacy of the drugs was assessed using the 4
      main symptoms of CPAO. Ankle-brachial index (ABI) also was measured as a clinical
      pharmacologic procedure. Adverse events were assessed throughout the study.
      RESULTS: A total of 124 patients (96 men, 28 women; mean [SD] age, 65 [12] years)
      were enrolled in 3 hospitals. Data from 119 patients (93 men, 26 women; mean [SD]
      age, 65 [12] years) were included in the efficacy analysis (64 and 55 patients in
      the beraprost and ticlopidine groups, respectively). Although all 4 symptoms of
      CPAO were ameliorated after 3 and 6 weeks of treatment with both drugs, only the
      cool sensation was significantly improved with beraprost compared with
      ticlopidine at 6 weeks (P<0.05). ABI was significantly increased with both
      beraprost and ticlopidine at 6 weeks versus baseline (P<0.001 and P<0.01,
      respectively), suggesting that this pharmacologic action may have led to their
      beneficial effect on various symptoms. The tolerability analysis included 123
      patients (65 and 58 patients in the beraprost and ticlopidine groups,
      respectively). The numbers of patients who (1) experienced adverse events (AEs),
      (2) experienced adverse drug reactions, and (3) withdrew due to AEs were
      significantly smaller in the beraprost group than in the ticlopidine group
      (P<0.001, P<0.05, and P<0.05, respectively). CONCLUSIONS: In this study
      population of patients with CPAO, beraprost ameliorated cool sensation in the
      limbs, intermittent claudication, limb pain, and ischemic/leg ulcers. Beraprost
      was more efficacious in relieving CPAO symptoms and was better tolerated than
      ticlopidine. Beraprost may be useful for the treatment of patients with CPAO, but
      more studies are needed.

PMID- 24944400
TI  - Intravenous lysine clonixinate for the acute treatment of severe migraine
      attacks: a double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown
      to be effective in the treatment of migraine. However, few commercially available
      NSAIDs can be administered IV. Lysine clonixinate (LC), an NSAID derived from
      nicotinic acid, has been proved effective in various algesic syndromes (eg, renal
      colic, muscular pain, nerve compression, odontalgia). The oral formulation of LC
      has been shown to be effective in the treatment of migraine of moderate severity.
      OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of
      the IV formulation of LC in the treatment of severe migraine. METHODS: This
      double-blind, randomized, placebo-controlled, prospective study enrolled patients
      with severe migraine (without aura) as defined by the criteria of the
      International Headache Society. When patients presented to a neurology hospital
      with an outpatient headache unit (Instituto de Neurologia Deolindo Couto, Rio de
      Janeiro, Brazil) with a severe migraine attack that had lasted <4 hours, they
      were randomized to 1 of 2 groups (IV placebo [25 mL of 0.9% saline] or IV LC [21
      mL of 0.9% saline plus 4 mL of LC 200 mg]). Headache intensity and adverse
      effects (AEs) were assessed before (0 minute) and 30, 60, and 90 minutes after
      study drug administration. Rescue medication was available 2 hours after study
      drug administration, and its use was compared between groups. RESULTS: Thirty-two
      patients (23 women, 9 men; mean [SD] age, 32 [2] years; range, 18-58 years)
      entered the study. Twenty-nine patients (21 women, 8 men; mean [SD] age, 32 [2]
      years; range, 18-56 years) completed the study. Three patients (all in the
      placebo group) did not complete the study (1 patient was unable to rate the pain
      severity after drug administration and 2 patients refused IV drug
      administration). Among study completers, 17 patients received LC and 12 placebo.
      At 30 minutes, 1 patient (8.3%) in the placebo group and 5 patients (29.4%) in
      the LC group were pain free; the between-group difference was not statistically
      significant. At 60 and 90 minutes, respectively, 3 (25.0%) and 5 (41.7%) patients
      in the placebo group and 12 (70.6%) and 14 (82.4%) patients in the LC group were
      pain free (P = 0.021 and P = 0.028 between groups at 60 and 90 minutes,
      respectively). Six patients (50.0%) in the placebo group and 1 patient (5.9%) in
      the LC group required rescue medication at 2 hours (P = 0.010 between groups).
      Three patients (25.0%) in the placebo group experienced AEs, including vomiting,
      dizziness, and malaise (1 patient [8.3%] each); 11 patients (64.7%) in the LC
      group experienced 1 AE, including burning pain at the injection site (5 patients
      [29.4%]), heartburn (4 patients [23.5%]), and dizziness and malaise (1 patient
      [5.9%] each) (P = 0.025). CONCLUSIONS: NSAIDs administered by the IV route cannot
      be used routinely in an outpatient environment, although an attempt to improve
      drugs in this class is clearly justified. This study demonstrated that IV LC was
      effective and well tolerated in the treatment of severe migraine attacks. This
      finding differs from results with the oral formulation, which is effective only
      in migraine of moderate severity.

PMID- 24944401
TI  - A randomized, double-blind comparison of granisetron alone and combined with
      dexamethasone for post-laparoscopic cholecystectomy emetic symptoms.
AB  - BACKGROUND: Granisetron hydrochloride, a selective serotonin receptor antagonist,
      has been used to treat established postoperative nausea and vomiting (PONV).
      Dexamethasone has been shown to reduce the incidence of chemotherapy-induced
      emesis when added to an antiemetic regimen. OBJECTIVE: The aim of this study was
      to examine the differences in efficacy and tolerability between the combination
      of granisetron plus dexamethasone and granisetron alone for the treatment of
      PONV. METHODS: This study was a randomized, double-blind trial conducted at
      Toride Kyodo General Hospital (Toride, Ibaraki, Japan). Men and women aged 25 to
      65 years and experiencing emetic symptoms after laparoscopic cholecystectomy were
      eligible for the study. Patients received IV therapy with either granisetron 40
      MUg/kg alone or with dexamethasone 8 mg. Patients were observed for 24 hours.
      Emetic episodes and the need for a rescue antiemetic were recorded by nursing
      staff, who were blinded to treatment assignment. RESULTS: One hundred patients
      (63 women, 37 men; mean [SD] age, 47 [10] years; range, 25-65 years) were
      enrolled; 50 patients were randomized to each treatment group. No significant
      differences in baseline demographic or clinical characteristics were observed
      between the groups. Complete control of established PONV, defined as no emetic
      symptoms and no need for another rescue antiemetic medication, occurred in
      significantly more patients who received the combination (49/50 [98%]) than in
      those who received granisetron alone (41/50 [82%]) (P = 0.008). No clinically
      important adverse effects due to the study drugs were observed in either group.
      CONCLUSION: In this study population of patients experiencing post
      cholecystectomy emesis, the combination of granisetron plus dexamethasone was
      more efficacious than granisetron alone for the treatment of PONV. Tolerability
      between the 2 treatments was similar.

PMID- 24944402
TI  - Effects of policosanol on borderline to mildly elevated serum total cholesterol
      levels: a prospective, double-blind, placebo-controlled, parallel-group,
      comparative study.
AB  - BACKGROUND: Hypercholesterolemia is a major risk factor for coronary heart
      disease. Clinical studies have shown that lowering elevated serum cholesterol
      levels, particularly low-density lipoprotein cholesterol (LDL-C), is beneficial
      for patients with borderline to mildly elevated serum total cholesterol (TC)
      levels (5.0-6.0 mmol/L). Policosanol is a cholesterol-lowering drug made from
      purified sugar cane wax. The therapeutic range of policosanol is 5 to 20 mg/d.
      OBJECTIVE: This study investigated the efficacy and tolerability of policosanol 5
      mg/d in patients with borderline to mildly elevated serum TC levels. METHODS:
      This 14-week, single-center, prospective, double-blind, placebo-controlled,
      parallel-group, comparative study was conducted in men and women aged 25 to 75
      years with a serum TC level >=4.8 to <6.0 mmol/L. After a 6-week run-in period in
      which patients were placed on therapeutic lifestyle changes, in particular a
      cholesterol-lowering diet, patients were randomly assigned to receive policosanol
      5-mg tablets or placebo tablets once daily with the evening meal for 8 weeks, and
      the diet was continued throughout the study. Lipid profile variables, safety
      indicators, adverse events (AEs), and compliance with study medications were
      assessed. RESULTS: One hundred patients (71 women, 29 men; mean [SD] age, 52 [10]
      years) entered the study after the dietary run-in period. After 8 weeks of
      treatment, the mean (SD) serum LDL-C level decreased significantly in the
      policosanol group (P<0.001 vs baseline and placebo) from 3.57 (0.30) mmol/L to
      2.86 (0.41) mmol/L (change, -19.9%). Significantly more patients in the
      policosanol group (42 patients [84%]) achieved a >=15% decrease in serum LDL-C
      than in the placebo group (2 patients [4%]) (P<0.001). Also in the policosanol
      group, the mean (SD) serum TC level decreased significantly, from 5.20 (0.22)
      mmol/L to 4.56 (0.44) mmol/L (P<0.001 vs baseline and placebo) (change, -12.3%);
      the mean (SD) triglyceride (TG) level decreased significantly, from 1.59 (0.57)
      mmol/L to 1.48 (0.57) mmol/L (P<0.01 vs baseline; P<0.05 vs placebo) (change, 
      6.9%); and the mean (SD) high-density lipoprotein cholesterol (HDL-C) level
      increased significantly from 1.05 (0.18) mmol/L to 1.16 (0.21) mmol/L (P<0.001 vs
      baseline and placebo) (change, +10.5%). The percentage changes were significantly
      different between the policosanol and placebo groups for serum LDL-C, TC, and HDL
      C levels (P<0.001, P<0.001, and P<0.05, respectively), but not for TG. In the
      placebo group, changes in lipid profile variables from baseline were not
      significant. Policosanol did not significantly impair any safety indicator and
      was well tolerated. Three patients (3%) (1 patient [2%] in the policosanol group;
      2 patients [4%] in the placebo group) withdrew from the trial, none because of
      AEs. Two patients (1 patient [2%] each in the policosanol and placebo groups)
      withdrew from the study because of an unwillingness to return for follow-up; 1
      patient (2%) in the placebo group had a change of address and could not be
      followed up. Overall, 4 patients (4%) (1 patient [2%] in the policosanol group; 3
      [6%], placebo) reported AEs; all were mild. Of the patients who received placebo
      and reported AEs, all 3 (6%) experienced heartburn, and 1 (2%) also experienced
      dry skin, while the policosanol-treated patient (2%) who reported an AE
      experienced headache. CONCLUSIONS: In this study of patients with borderline to
      mildly elevated serum TC levels, based on the criterion that >=70% of policosanol
      treated patients reached the LDL-C goal of a decrease >=15% from baseline
      whenever this proportion was different with respect to placebo, 8 weeks of
      treatment with policosanol 5 mg/d was effective. The decreased LDL-C, TC, and TG
      levels, increased HDL-C level, and good tolerability found with this treatment
      support its use in such patients.

PMID- 24944403
TI  - Analysis of West Virginia medicaid claims data for the prevalence of medical
      conditions and use of drugs likely to cause QT prolongation in patients with
      schizophrenia.
AB  - BACKGROUND: An important concern with antipsychotic drugs used for the treatment
      of schizophrenia is the prolongation of the QT interval on the electrocardiogram.
      Concomitant use of other QT-prolonging drugs and the presence of certain medical
      conditions may lead to excessive QT prolongation and subsequent cardiac
      arrhythmias. OBJECTIVE: The aim of this study was to assess the utilization of QT
      prolonging drugs and the prevalence of medical conditions causing QT prolongation
      in a large population of patients with schizophrenia in practice settings.
      METHODS: The study was conducted using West Virginia Medicaid claims data for
      patients aged 18 to 64 years with >=1 medical claim for schizophrenia between
      January 1, 1997, and December 31, 1999. A comprehensive list of drugs and medical
      conditions causing QT prolongation was obtained from the literature. The drugs
      were identified in the prescription claims data using their specific National
      Drug Classification codes. Codes from the International Classification of
      Diseases, Ninth Revision, Clinical Modification, were used to identify the
      medical conditions as described in the medical claims files. Descriptive
      statistics on utilization of drugs and prevalence of medical conditions were
      reported and demographic differences were examined. RESULTS: The final sample
      consisted of 1699 patients with schizophrenia. The mean (SD) age was 40.8 (11.35)
      years (range, 18-63 years); 55% of the patients were women. A total of 76.9% of
      patients utilized >=1 nonantipsychotic QT-prolonging drug in a year, with a mean
      (SD) of 2.1 (1.3) such drugs used per patient per year. A total of 15.9% of
      patients with schizophrenia had >=1 medical condition associated with QT
      prolongation. Patients with >=1 such medical condition had a mean (SD) of 1.2
      (0.57) conditions potentially causing QT prolongation. The number of
      nonantipsychotic QT-prolonging prescriptions filled and the prevalence of medical
      conditions leading to QT prolongation were found to be significantly higher for
      women (both P<0.001) and patients aged 34 to 64 years (both P<0.001).
      CONCLUSIONS: In this study, a high utilization of QT-prolonging drugs and the
      prevalence of medical conditions causing QT prolongation were found. These
      results merit assessment of predisposing risk factors, such as concurrent use of
      other QT-prolonging drugs and the presence of cardiovascular and other conditions
      associated with QT prolongation, before prescribing antipsychotics, especially in
      women and older patients with schizophrenia.

PMID- 24944405
TI  - Effect of betamethasone on the expression of dopamine D1 receptor mRNA in the
      developing rabbit adrenal gland.
AB  - BACKGROUND: Antenatal corticotherapy is widely used to enhance pulmonary fetal
      maturation in cases in which premature birth is likely. The adrenal gland, which
      has a key role in controlling fetal and neonatal adaptation, appears to be a
      target organ of glucocorticoids. OBJECTIVES: The aim of this study was first to
      determine the ontogenic profile of dopamine D1 receptor (DA D1-R) messenger RNA
      (mRNA) in the rabbit. The effects of antenatal exposure to exogenous corticoids
      on levels of adrenal DA D1-R mRNA expression were examined. METHODS: Pregnant
      rabbits free of any treatment or handling before delivery were chosen for the
      study of DA D1-R mRNA ontogenic profile. For the study of the antenatal exposure
      to exogenous corticoids, pregnant rabbits were given 2 injections of either
      betamethasone 0.1 mg/kg or saline 0.1 mL/kg. DA D1-R mRNA expression was
      determined using northern blot analysis at 4 developmental ages: fetus (at 27
      days of gestation), 1 day of age, 25 days of age, and adulthood. Rabbits were
      allocated to their respective group (treated or untreated) depending on maternal
      treatment (betamethasone or saline, respectively). RESULTS: Four pregnant rabbits
      were used for the ontogenic-profile group, which comprised 11 fetuses, seven 1
      day-old rabbits, four 25-day-old rabbits, and 2 adults. Six other pregnant
      rabbits received betamethasone; 6 saline. The treated group comprised 12 fetuses,
      twelve 1-day-old rabbits, four 25-day-old rabbits, and 3 adults. The untreated
      group comprised 12 fetuses, fifteen 1-day-old rabbits, five 25-day-old rabbits,
      and 3 adults. DA D1-R mRNA was expressed in rabbit adrenal glands from the fetal
      period to adulthood and this expression was not age dependent. Moreover,
      antenatal corticotherapy induced a significant increase in respective DA D1-R
      mRNA levels of 20%, 15%, and 8% in treated fetuses, 1-day-old rabbits, and 25-day
      old rabbits compared with the untreated groups (P <0.003, 0.003, and 0.005,
      respectively). This increase was not observed in adulthood. CONCLUSIONS: In the
      rabbits in this study, DA D1-R mRNA expression in the adrenal gland began during
      gestation. Its expression was not age dependent but was rapidly modified by
      antenatal exposure to betamethasone. These corticoid-induced changes, observed
      until late infancy, did not occur in adulthood.

PMID- 24944404
TI  - Effects of garcinia cambogia (Hydroxycitric Acid) on visceral fat accumulation: a
      double-blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: (-)-Hydroxycitric acid (HCA) is an active ingredient extracted from
      the rind of the Indian fruit Garcinia cambogia. It inhibits adenosine
      triphosphate citrate lyase and has been used in the treatment of obesity.
      OBJECTIVE: The primary end point of this study was the effects of 12 weeks of G
      cambogia extract administration on visceral fat accumulation. The secondary end
      points were body indices (including height, body weight, body mass index [BMI],
      waist and hip circumference, and waist-hip ratio) and laboratory values
      (including total cholesterol, triacylglycerol, and free fatty acid). METHODS:
      This study was performed according to a double-blind, randomized, placebo
      controlled, parallel-group design. Subjects aged 20 to 65 years with a visceral
      fat area >90 cm(2) were enrolled. Subjects were randomly assigned to receive
      treatment for 12 weeks with G cambogia (containing 1000 mg of HCA per day) or
      placebo. At the end of the treatment period, both groups were administered
      placebo for 4 weeks to assess any rebound effect. Each subject underwent a
      computed tomography scan at the umbilical level at -2, 0, 12, and 16 weeks.
      RESULTS: Forty-four subjects were randomized at baseline, and 39 completed the
      study (G cambogia group, n = 18; placebo group, n = 21). At 16 weeks, the G
      cambogia group had significantly reduced visceral, subcutaneous, and total fat
      areas compared with the placebo group (all indices P<0.001). No severe adverse
      effect was observed at any time in the test period. There were no significant
      differences in BMI or body weight at week 12, but there were slight numeric
      decreases in body weight and BMI in men. There were no signs of a rebound effect
      from week 12 to week 16. CONCLUSION: G cambogia reduced abdominal fat
      accumulation in subjects, regardless of sex, who had the visceral fat
      accumulation type of obesity. No rebound effect was observed. It is therefore
      expected that G cambogia may be useful for the prevention and reduction of
      accumulation of visceral fat.

PMID- 24944406
TI  - Effects of food on the bioavailability of gepirone from extended-release tablets
      in humans: results of two open-label crossover studies.
AB  - BACKGROUND: The new antidepressant gepirone acts preferentially on 5
      hydroxytryptamine type 1A (5-HT1A) receptors and functions as a 5-HT1A agonist.
      Placebo-controlled clinical studies have established that gepirone has a good
      safety profile and is effective for the treatment of depression. A previous study
      showed that administration of gepirone immediate release 15 minutes after a meal
      instead of during a fast increased the mean area under the plasma concentration
      time curve (AUC) by 37%. Gepirone was reformulated into extended release (ER),
      which necessitated further exploration of the effects of food on bioavailability.
      OBJECTIVE: This article describes 2 studies of the pharmacokinetic properties of
      gepirone ER and 1 of its metabolites, 1(2-pyrimidinyl)-piperazine (1-PP), in
      healthy subjects. In study 1, we assessed the effects of food and the influence
      of time of food intake relative to dosing on the bioavailability of gepirone ER.
      The objective of study 2 was to confirm that gepirone ER has similar
      pharmacokinetic characteristics under fed and fasting conditions. METHODS: Two
      open-label, randomized, single-dose, crossover studies balanced for first-order
      residual effects were conducted to assess the bioavailability of gepirone from ER
      tablets. Healthy male subjects received a 20-mg oral dose of gepirone ER. In
      study 1, subjects took the gepirone ER dose after a 10-hour overnight fast or 1
      hour before, 15 minutes after, or 2 hours after a standard high-fat meal. In
      study 2, subjects either took the gepirone ER dose after a 10-hour overnight fast
      and continued to fast for 4 more hours or took the gepirone ER dose 15 minutes
      after a standard high-fat meal. RESULTS: Twenty-eight men (mean [SD] age, 27.2
      [6.6] years) participated in study 1, and 27 men (mean [SD] age, 31.8 [9.6]
      years) participated in study 2. In study 1, the mean (SD) maximum peak plasma
      concentration (Cmax) for gepirone ER was 69.2% higher (3.25 [1.71] vs 1.92 [0.96]
      ng/mL) (P<=0.05) and the AUC from time 0 to 30 hours for gepirone ER was 31.9%
      higher (39.3 [20.6] vs 29.8 [15.3] ng/mL.h) (P<=0.05) for the 15-minute
      postprandial dose than for the fasting dose, respectively. In study 2, the mean
      Cmax for gepirone was 62.0% higher (4.13 vs 2.55 ng/mL) and the mean AUC from
      time 0 to infinity for gepirone was 24% higher (38.71 vs 31.14 ng/mL.h) for the
      postprandial dose than for the fasting dose (P<0.05). All reported adverse
      effects were mild to moderate in intensity, and most (study 1) or all (study 2)
      occurred during the fasting state. CONCLUSIONS: When administered with food, the
      bioavailability (AUC and Cmax) of gepirone ER was greater than during the fasting
      state, with the greatest bioavailability seen when the drug was taken 15 minutes
      after eating. Based on this pharmacokinetic analysis, it may be prudent to
      administer gepirone ER consistently, either always with or always without food.

PMID- 24944407
TI  - Prospective, randomized comparison of OM-85 BV and a prophylactic antibiotic in
      children with recurrent infections and immunoglobulin A and/or G subclass
      deficiency.
AB  - BACKGROUND: Patients with immunoglobulin (Ig)A and/or IgG subclass deficiency may
      be asymptomatic or may have recurrent, mainly respiratory infections. OBJECTIVE:
      This study compared the clinical efficacy and tolerability of prophylactic
      therapy with either the oral immunomodulator bacterial extract OM-85 BV or
      benzathine penicillin G (BPG) in the prevention of recurrent infections in
      symptomatic patients. METHODS: In this 26-month, prospective, randomized study
      conducted at the Department of Pediatric Immunology, Ege University (Izmir,
      Turkey), children aged 1 to 12 years with recurrent infections and IgA and/or IgG
      subclass deficiency were enrolled. After an initial 12-month control period,
      patients were randomized to receive OM-85 BV or BPG. OM-85 BV (3.5-mg capsule)
      was given once daily for the first 10 days of each month for the first 3 months
      of the study. IM injections of BPG were given at a dose of 1.2 million units (for
      patients with body weight > 27 kg) or at a half-dose (for patients with body
      weight <=27 kg) every 3 weeks for 12 months. In nonresponders (ie, those who
      continued to have recurrent infections at 12-month follow-up), IV immunoglobulin
      (IVIG) replacement therapy at 400 mg/kg body weight was given every 4 weeks for
      an additional 12 months. The results of IVIG therapy were assessed by the authors
      using clinical observation. Adverse effects and adverse drug reactions were
      documented by the authors for each vaccine, prophylactic therapy, and IVIG.
      RESULTS: A total of 91 children (56 boys, 35 girls; mean [SD] age at the start of
      the control period, 46.4 [31.0] months) were enrolled. Of these, 44 were
      randomized to the OM-85 BV group and 47 to the BPG group. The year before
      prophylactic therapy, the mean (SD) number of reported infections was 10.7 (3.6)
      and the mean (SD) number of antibiotic courses was 9.7 (3.6) (OM-85 BV group:
      mean [SD] number of reported infections, 10.5 [3.3]; mean (SD) number of
      antibiotic courses, 9.3 [3.3]; BPG group: mean [SD] number of reported
      infections, 10.8 [3.9], mean (SD) number of antibiotic courses, 10.1 [3.9]). At
      12 months, the number of infections and antibiotic courses decreased
      significantly in the entire study population, but the between-group difference
      was not significant. Five patients in each group (OM-85 BV group, 11.4%; BPG
      group, 10.6%) were considered nonresponders and received IVIG treatment. Compared
      with responders, nonresponders were significantly younger (mean [SD] age, 34.40
      [21.70] months vs 52.65 [30.52] months; P = 0.036) and had lower serum IgG
      (P<0.001), IgG1 (P = 0.006), IgG2 (P = 0.003), IgG3 (P = 0.035), and IgM (P =
      0.008) levels and antibody responses to tetanus toxoid and Haemophilus influenzae
      type b (Hib) vaccines (P = 0.036 and 0.013, respectively). At 12-month follow-up,
      a protective effect of the prophylactic IVIG therapy was seen, with a
      statistically significant reduction in the number of infections to 3.3 (2.4) and
      in the number of antibiotic courses to 2.7 (2.5) (both P = 0.005). CONCLUSIONS:
      In this study population of children with recurrent infections and IgA and/or IgG
      subclass deficiency, prophylactic therapy with either OM-85 BV or an antibiotic
      significantly decreased the number of infections per year. In addition,
      nonresponders benefited from IVIG replacement therapy.

PMID- 24944408
TI  - Effects of pyrimethamine versus proguanil in malarial chemoprophylaxis in
      children with sickle cell disease: a randomized, placebo-controlled, open-label
      study.
AB  - BACKGROUND: Malarial chemoprophylaxis is essential for patients with homozygous
      sickle cell disease (SCD) who live in areas where malaria is endemic. Endemic
      regions include most sub-Saharan African countries and Southeast Asia. OBJECTIVE:
      This study compared the efficacy and tolerability of pyrimethamine with that of
      proguanil and placebo in the prevention of malaria and the complications of
      Plasmodium falciparum infection (hepatomegaly, splenomegaly, bone pain crisis,
      hemolytic crisis) in children with SCD. METHODS: In this single-center, open
      label study conducted in Nigeria, children aged 1 to 16 years with SCD were
      randomly assigned to receive tablets of pyrimethamine (0.5 mg/kg.wk), proguanil
      (1.5 mg/kg.d), or placebo (vitamin C, 7 mg/kg.d) for 9 months as prophylaxis from
      February to December (which includes the rainy season), the period of greatest
      malarial transmission. The clinical and laboratory features of malaria (presence
      of parasitemia, parasite count and density, hepatomegaly and/or splenomegaly,
      symptomatic malarial infection [fever, rigors], bone pain crises, and hemolytic
      crises) were assessed. RESULTS: A total of 97 patients completed the study (49
      boys, 48 girls; mean [SD] age, 7.8 [4.3] years). The pyrimethamine group
      comprised 36 patients (mean [SD] age, 8.1 [4.3] years; range, 2-16 years); the
      proguanil group, 32 patients (mean [SD] age, 9.5 [3.7] years; range, 3-16 years);
      and the placebo group, 29 patients (mean age, 5.9 years; range, 1-14 years). The
      male:female ratio was 1.1:1 in the pyrimethamine group, 1:1.7 in the proguanil
      group, and 1.6:1 in the placebo group. Parasitemia was noted in 7 patients
      (19.4%) in the pyrimethamine group, 6 (18.8%) in the proguanil group, and 7
      (24.1%) in the placebo group at the start of the study. P falciparum was the only
      isolate. The mean parasite density over the 9-month period was significantly
      lower with proguanil compared with pyrimethamine (P = 0.045) and placebo
      (P<0.05). The incidence of splenomegaly was least with pyrimethamine, but this
      group had the most patients clinically diagnosed with malaria. Hospitalizations
      and episodes of bone pain and hemolytic crisis occurred most frequently with
      placebo. One patient in the placebo group died of septicemia. CONCLUSIONS:
      Proguanil and pyrimethamine both reduced parasitemia; however, proguanil
      significantly decreased mean parasite density more effectively than
      pyrimethamine. Pyrimethamine and proguanil may protect children with SCD from the
      complications of P falciparum infection despite persistent parasitemia. Proguanil
      may be more useful than pyrimethamine in the prevention of bone pain crises among
      patients with SCD.

PMID- 24944409
TI  - Treatment of complex regional pain syndrome type 1 in a pediatric patient using
      the lidocaine patch 5%: a case report.
AB  - BACKGROUND: Successful treatment of complex regional pain syndrome type 1 (CRPS
      1) requires a coordinated, multidisciplinary approach. Physical rehabilitation is
      an important component of long-term treatment. Unfortunately, patients with
      significant allodynia or hyperalgesia characteristic of CRPS-1 often have
      difficulty progressing through a physical therapy (PT) regimen. In most adults
      with CRPS-1, the treatment of choice is PO opioids. OBJECTIVE: This article
      presents a case report of the use of the lidocaine patch 5%, a targeted
      peripheral analgesic, in a pediatric patient and its effects on reducing pain,
      improving the patient's overall attitude, and facilitating compliance with
      ongoing PT. RESULTS: A 10-year-old girl developed CRPS-1 after arthroscopic
      surgery for a sprained ankle. Attempts at PT were unsuccessful due to inadequate
      pain relief from various treatment modalities. Therapy with the lidocaine patch
      5% was initiated and resulted in significant pain relief, improvements in the
      patient's attitude, and progress with PT. CONCLUSION: This case report of a child
      with CRPS-1 showed that therapy with lidocaine patch 5% may be efficacious in
      treating children with pain resulting from CRPS-1, thereby increasing the success
      of PT.

PMID- 24944410
TI  - Finding clues through meta-analysis.

PMID- 24944412
TI  - Doing a review-His way.

PMID- 24944411
TI  - A retrospective meta-analysis of the efficacy and tolerability of fenofibrate 300
      mg/d on high-density lipoprotein cholesterol levels in randomized, double-blind,
      comparative studies conducted in Japan.
AB  - BACKGROUND: Low levels of plasma high-density lipoprotein cholesterol (HDL-C)
      represent an important risk factor for coronary heart disease (CHD). Increasing
      HDL-C by 1 mg/dL decreases the incidence of CHD by 2% to 3%. Fenofibrate
      increases HDL-C by ~23%, to >=40 mg/dL, and may be effective in preventing CHD.
      OBJECTIVE: The aim of this study was to assess the effects of fenofibrate on HDL
      C in patients treated for 12 weeks in 3 randomized, double-blind, comparative
      studies conducted in Japan. Changes in total cholesterol (TC) and triglycerides
      (TG), effects on HDL-C and apolipoprotein (apo) A-I and A-II by TG level, and
      effects on serum lipid levels by type of hyperlipidemia were the secondary end
      points. METHODS: Changes in HDL-C levels, as well as TC and TG levels, were
      analyzed in patients who received fenofibrate 300 mg/d for 12 weeks. Patients
      aged 20 to 80 years with mean TC >=220 mg/dL (hypercholesterolemia), TG >=150
      mg/dL (hypertriglyceridemia), or both (combined hyperlipidemia) were considered
      assessable. RESULTS: In this retrospective meta-analysis conducted at Grelan
      Pharmaceutical Co. Ltd. (Tokyo, Japan), data from 263 patients (137 women, 126
      men; mean [SD] age, 56.0 [10.8] years; range, 25-79 years) were included. The
      mean (SD) HDL-C level increased significantly, from 46.1 (0.9) mg/dL to 55.9
      (1.0) mg/dL after 12 weeks of treatment with fenofibrate (P<0.001). Serum TC and
      TG decreased significantly (both P<0.001). HDL-C elevation was greater in
      patients with TG >=150 mg/dL than in patients with TG<150 mg/dL, although apo A-I
      and A-II changes were the same in both groups. HDL-C increased in every type of
      hyperlipidemia, 14.9% in hypercholesterolemia, 22.0% in hypertriglyceridemia, and
      33.5% in combined hyperlipidemia. Baseline HDL-C levels were <40 mg/dL in 93
      patients (group 1) and >=40 mg/dL in 170 patients (group 2). Mean HDL-C levels
      increased significantly in both groups during the treatment period, from 32.6
      (0.6) mg/dL to 42.6 (1.0) mg/dL in group 1 and from 53.5 (0.9) mg/dL to 63.1
      (1.1) mg/dL in group 2 (both P<0.001). One patient (0.3%) of the 331 included in
      the tolerability analysis experienced a serious adverse effect (jaundice).
      CONCLUSION: In this study of patients with hypercholesterolemia,
      hypertriglyceridemia, or combined hyperlipidemia, 12-week treatment with
      fenofibrate 300 mg/d was effective and generally well tolerated, with the
      possible exception of transient changes in aminotransferases. HDL-C was increased
      in all patients to ~40 mg/dL, the target level.

PMID- 24944414
TI  - Reasons for overprescription of mononitrates: the paradigm of stable angina
      pectoris treatment.
AB  - BACKGROUND: Oral nitrates, beta-blockers, and calcium channel blockers are used
      to treat stable angina pectoris (SAP). The 2 therapeutic subtypes of oral
      nitrates are mononitrates and dinitrates, with no evidence that 1 subtype is more
      efficacious than the other. Although practice guidelines in Great Britain and
      Israel recommend dinitrates as the first-line drug for SAP, in practice, many
      physicians in those 2 countries prescribe mononitrates. OBJECTIVE: The aim of
      this study was to identify factors that influence specialist physicians (family
      practitioners, internists, and cardiologists) in Israel when prescribing nitrates
      for the prevention of SAP symptoms. METHODS: A group of specialists was given a
      self-administered questionnaire regarding their treatment of choice for a patient
      with SAP described in a hypothetical case vignette. End points for prescribing
      preferences were evidence-based information, cost, and the influence of
      pharmaceutical company representatives. RESULTS: One hundred ten specialists were
      given the questionnaire. Eighty-nine specialists (45 men, 44 women; mean age,
      50.4 years; range, 34-67 years; response rate, 80.9%) completed it (39 family
      practitioners, 29 internists, and 21 cardiologists). Seventy-eight respondents
      (87.6%) chose to prescribe nitrates for the case vignette, and among those, 54
      (69.2%) chose mononitrates and 24 (30.8%) chose dinitrates (P = 0.034). The
      choice of mononitrates over dinitrates was mainly affected by habit (25/54
      [46.3%]) and the belief that mononitrates are more effective, safer, and/or less
      expensive than dinitrates (21/54 [38.9%]). Drug costs for the patient
      significantly influenced more family practitioners than hospital specialists
      (P<0.05). CONCLUSIONS: In contrast to guideline recommendations, the paradigm of
      SAP treatment with nitrates in this study was characterized by significantly more
      prescriptions for mononitrates than dinitrates. This situation contributes to the
      erosion of the scarce resources of the health care system in Israel. Further
      efforts are needed to increase physicians' awareness of quality, cost, and
      choices when prescribing drugs.

PMID- 24944413
TI  - Efficacy and safety of levofloxacin in the context of other contemporary
      fluoroquinolones: a review.
AB  - BACKGROUND: In recent years, fluoroquinolone research has focused on achieving
      several goals, including (1) enhanced potency against gram-positive cocci,
      notably Streptococcus pneumoniae, and anaerobes, while (2) maintaining potency
      against gram-negative pathogens, (3) optimizing pharmacokinetics and
      pharmacodynamics (PK/PD), and (4) minimizing potential adverse drug reactions
      through recognition and avoidance of structural configurations that have
      characterized earlier, reactive compounds. OBJECTIVE: This review examines the
      efficacy and safety of fluoroquinolones and the specific clinical evidence
      regarding levofloxacin. METHODS: Using published literature collected over time
      by the author, a review was conducted, focusing on the efficacy and safety
      profile of levofloxacin and other fluoroquinolones. RESULTS: The newer
      fluoroquinolones have fulfilled many of the research goals described above.
      Levofloxacin has improved anti-gram-positive potency, PK/PD properties, a proven
      clinical trial record (particularly for communityacquired pneumonia [CAP]), and
      an excellent safety profile-in the context of the treatment of >250 million
      patients worldwide in the past decade. It is licensed for management of drug
      resistant S pneumoniae infections in the United States and has gained widespread
      formulary acceptance and guideline inclusion. Studies assessing levofloxacin for
      CAP therapy show significant advantages over standard therapy, such as trends
      toward reduced IV therapy and length of hospitalization, reduced mortality, and
      significant associated cost reduction. In addition, levofloxacin has proved
      highly effective in acute exacerbations of chronic bronchitis (AECB), with
      excellent clinical and bacteriologic results, typical of the class, and
      significant advantages-in terms of clinical response, overall pathogen
      eradication, extension of the symptom-free period, and trends toward a reduction
      in the number of consultation visits and hospitalizations-over standard agents,
      such as the oral cephalosporins. CONCLUSIONS: Levofloxacin offers a combination
      of documented efficacy and tolerability, and provides an important option for the
      treatment of bacterial infections, including CAP and AECB, compared with standard
      agents used in the management of lower respiratory tract infections.

PMID- 24944415
TI  - Guidelines for the clinical use of albumin: comparison of use in two Italian
      hospitals and a third hospital without guidelines.
AB  - BACKGROUND: In the absence of clinical practice guidelines prior to 1999, the
      consumption of human albumin in the Liguria region of Italy was very high,
      despite possible adverse effects, limited supply, and significant cost.
      OBJECTIVE: The purpose of this study was to assess the impact of comprehensive
      guidelines on the amount of albumin used in 2 general hospitals and to compare it
      with that of a third general hospital that did not adopt the guidelines. METHODS:
      We analyzed the influence of the guidelines on albumin use in 2 general hospitals
      (hospitals 1 and 2) in the Liguria region by comparing albumin consumption during
      the year before the distribution of the guidelines (1999) with consumption in the
      2 years after their distribution (2000 and 2001). We compared these data with
      those of a third general hospital that did not adopt the guidelines (hospital 3).
      The parameters considered were total consumption of albumin, consumption per bed,
      consumption per hospital stay, mean time to discharge, expenditure per bed, and
      mortality rate. RESULTS: In the years 2000 and 2001, the adoption of guidelines
      reduced albumin consumption in hospitals 1 and 2. In hospital 1, where the
      release of albumin was carefully controlled by the transfusion service, albumin
      use per hospital stay decreased 8.7% in 2000 and 7.6% in 2001 from 1999; in
      hospital 2, use decreased 73.8% and 77.4%, respectively, from 1999. In hospital
      3, rejection of the guidelines was coupled with an increase of 2.9% and 8.4%,
      respectively, in the amount of albumin used per hospital stay. In the years 2000
      and 2001, the savings in the expenditure for albumin was ~17,000 euro in hospital
      1 and ~200,000 euro in hospital 2. CONCLUSION: This study confirms that the
      adoption of guidelines may substantially reduce the inappropriate use of albumin
      and relative costs.

PMID- 24944416
TI  - Bioequivalence and tolerability study of two brands of clopidogrel tablets, using
      inhibition of platelet aggregation and pharmacodynamic measures.
AB  - BACKGROUND: The role of platelets in acute cardiovascular atherothrombotic events
      has been well established and attention has focused on platelet inhibition
      therapy. Clopidogrel is a novel thienopyridine inhibitor of adenosine diphosphate
      induced platelet activation. Recent studies have shown that in the setting of
      coronary angioplasty/stenting, a loading dose of 300 mg followed by 75 mg once
      daily is required for optimum benefit. OBJECTIVE: This study assessed the
      bioequivalence and tolerability of 2 oral formulations of clopidogrel 75-mg
      tablets. METHODS: This 10-day, open-label, randomized, parallel-group,
      comparative bioequivalence and tolerability study was carried out in the
      Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of
      Medical Sciences (Hyderabad, India). Young healthy male volunteers were enrolled.
      Subjects were randomized to receive one of two 75-mg tablet formulations of
      clopidogrel (Clopivas((r)) [test formulation] or Plavix((r)) [reference
      formulation]). Subjects first received a 300-mg loading dose (four 75-mg tablets)
      on day 1, followed by 75 mg (1 tablet) at 8:00 AM daily for the next 6 days.
      Inhibition of platelet aggregation, which is the pharmacologic basis for the
      therapeutic efficacy of antiplatelet agents, and the effect on bleeding time were
      used as the pharmacodynamic assessment criteria. Pharmacodynamic variables
      included mean of maximum activity of percentage of inhibition of platelet
      aggregation (Emax), mean time to reach Emax (tmax), and mean area under the
      activity-time curve from time 0 to 168 hours (AUC0-168). Tolerability assessments
      included blood pressure and heart rate measurements before and at regular
      intervals (every hour for 12 hours and then at 24 hours) over a 24-hour period
      after drug administration. Clinical tolerability was assessed using adverse
      effects, platelet count (assessed on days 3, 6, and 10 after first-dose
      administration), and neutrophil count (assessed on day 10 after first-dose
      administration). RESULTS: Twenty subjects were enrolled (mean [SD] age, 26.5
      [2.9] years [range, 22-32 years]). Emax, tmax, and AUC0-168 were similar between
      the 2 groups, as was bleeding time. The 90% CIs were within the bioequivalence
      acceptance range of 80% to 125%. One subject (10%) in the Plavix group
      experienced mild headache; no serious adverse effects were reported, and none of
      the subjects dropped out due to an adverse effect. Platelet and neutrophil counts
      were found to be within normal limits. CONCLUSIONS: In this study of healthy male
      volunteers, the 2 tablet preparations of clopidogrel showed bioequivalence.
      However, the sample size was smaller than that generally recommended for a
      bioequivalence study, and additional studies with larger sample sizes are needed.

PMID- 24944417
TI  - Increased serum triglyceride clearance and elevated high-density lipoprotein 2
      and 3 cholesterol during treatment of primary hypertriglyceridemia with
      bezafibrate.
AB  - BACKGROUND: Hypertriglyceridemia accompanied by low levels of high-density
      lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease.
      High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the
      progress of atherosclerosis through reverse cholesterol transport. As a result,
      peripheral tissues can be protected against excessive accumulation of
      cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C,
      results are not standardized regarding increases of HDL3 and HDL2 subfractions.
      OBJECTIVE: This study assessed the effects of bezafibrate on serum triglyceride
      (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and
      HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum
      TG >=150 mg/dL). METHODS: Outpatients with primary hypertriglyceridemia were
      enrolled in this 8-week study conducted at the Third Department of Internal
      Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was
      administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8
      weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C,
      and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and
      measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic
      triglyceride lipase (HTGL) activity in postheparin plasma were performed before
      bezafibrate administration and after the course of treatment. RESULTS: Sixteen
      patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30-69 years];
      mean [SD] body mass index, 23 [2] kg/m(2)) entered the study. The following
      findings were observed in male and female patients after 8 weeks of treatment. A
      statistically significant reduction was observed in mean serum TG level (P<0.01).
      Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2
      (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and
      HTGL activity did not change significantly. No adverse effects related to the use
      of bezafibrate were documented. CONCLUSIONS: In this study, bezafibrate treatment
      resulted in significant decreases in serum TG level and significant increases in
      HDL2-C and HDL3-C levels and plasma LPL mass and activity. We hypothesize that
      bezafibrate may increase HDL3-C by promoting TG-rich lipoprotein catabolism and
      may increase HDL2-C by promoting the conversion of HDL3 to HDL2.

PMID- 24944418
TI  - Effects of efonidipine, an L- and T-Type dual calcium channel blocker, on heart
      rate and blood pressure in patients with mild to severe hypertension: an
      uncontrolled, open-label pilot study.
AB  - BACKGROUND: Dihydropyridines (DHPs), a type of calcium channel blocker (CCB), are
      commonly prescribed for the treatment of hypertension and angina pectoris. DHPs
      act mainly on L-type calcium channels, essentially causing reflex tachycardia
      (elevated heart rate [HR]), which negatively affects cardiac function. Because T
      type calcium channels in the sinoatrial node attenuate reflex tachycardia, a dual
      L- and T-type CCB (eg, efonidipine hydrochloride) may favorably affect cardiac
      pacing, thereby reducing reflex tachycardia. The effect of efonidipine as a DHP
      on HR deserves special consideration with regard to reflex tachycardia.
      OBJECTIVE: The aim of this study was to determine whether the L- and T-type CCB
      efonidipine can decrease the elevated HR induced by prior treatment using
      traditional DHPs. METHODS: This uncontrolled, open-label pilot study was
      conducted at the Division of Cardiology, Department of Internal Medicine, The
      Jikei University School of Medicine (Tokyo, Japan). Patients aged 48 to 80 years
      with mild to severe hypertension and angina pectoris and who were receiving
      therapy with a DHP other than efonidipine were eligible. During an 8-week
      observation period, patients continued therapy with their DHP. After those 8
      weeks, therapy was switched to oral efonidipine (40-mg tablet once daily) in
      patients whose blood pressure (BP) was stable and well controlled and whose HR
      was >80 bpm. BP and HR were monitored every 4 weeks of treatment with
      efonidipine. RESULTS: Eighteen patients (12 men, 6 women; mean [SD] age, 62.6
      [12] years) were enrolled. After the switch to efonidipine, mean (SD) HR
      decreased significantly, from 94 (7) bpm to 86 (11) bpm at 12 weeks (P<0.05). The
      antihypertensive effect of efonidipine was similar to that of the DHPs used
      before the switch to efonidipine therapy, and reflex tachycardia was attenuated.
      CONCLUSION: In this study of a small sample of patients with mild to severe
      essential hypertension and angina pectoris, efonidipine was as effective as other
      DHPs. Moreover, the drug attenuated the reflex tachycardia that occurred with
      traditional DHPs.

PMID- 24944419
TI  - Effects of low-dose combination therapy with an angiotensin-converting enzyme
      inhibitor and a diuretic on flow-mediated vasodilation in hypertensive patients:
      a 6-month, single-center study.
AB  - BACKGROUND: Combination therapy with an angiotensin-converting enzyme (ACE)
      inhibitor and a diuretic has been shown to be highly effective in hypertension.
      Clinical trials have demonstrated that ACE inhibitors may improve endothelial
      cell dysfunction in hypertension. However, the effectiveness of the combination
      treatment in endothelial cell dysfunction is unknown. OBJECTIVE: This study
      investigated the effects of a new low-dose combination, perindopril 2 mg plus
      indapamide 0.625 mg, on brachial artery flow-mediated vasodilation (FMD) and left
      ventricular diastolic function in hypertension. METHODS: Patients aged 18 to 75
      with newly diagnosed stage I or II hypertension were eligible. Endothelium
      dependent brachial artery FMD and endothelium-independent vasodilation were
      assessed at baseline. Patients were treated with oral perindopril 2 mg plus
      indapamide 0.625-mg tablets once daily for 6 months. FMD measurements were then
      repeated. Percentage changes in FMD from baseline to 6 months, as well as left
      ventricular diastolic function parameters (isovolumic relaxation time [IVRT] and
      mitral diastolic E-wave deceleration time [EDT]), indicated the effectiveness of
      the intervention. RESULTS: Twenty-nine Turkish patients were enrolled (17 women,
      12 men; mean [SD] age, 54.5 [9.5] years [range, 38-75 years]). The mean (SD)
      baseline FMD was 7.00% (2.39%) (endothelial cell dysfunction) and increased
      significantly to 8.68% (2.78%) at 6 months (P = 0.02); FMD improved in 15
      patients (51.7%). At baseline and 6 months of therapy, mean (SD) IVRT was 101.7
      (12.4) ms and 95.5 (7.7) ms, respectively (P<0.001), and EDT was 234.7 (33.9) ms
      and 217.9 (25.6) ms, respectively (P<0.001). CONCLUSIONS: In this small sample of
      hypertensive patients, a low-dose combination ACE inhibitor and diuretic
      significantly improved brachial artery FMD and left ventricular diastolic
      function. The improvement in FMD values was independent of the stage of
      hypertension. These findings suggest a relationship between improvement in
      endothelial cell function and diastolic function.

PMID- 24944420
TI  - Treatment of diaphragmatic fatigue with inhaled aminophylline therapy in an
      experimental canine model: an open-label, dose-ranging, pharmacologic study.
AB  - BACKGROUND: Diaphragmatic fatigue may contribute to the development of
      respiratory failure. Although aminophylline administered IV has been widely used
      to treat diaphragmatic fatigue, to date it has not been used in aerosol
      formulation for this purpose. OBJECTIVE: The aim of this study was to assess the
      efficacy of inhaled aminophylline on contractility of fatigued diaphragm in an
      experimental canine model. METHODS: This open-label, dose-ranging, pharmacologic
      study was conducted at the Department of Anesthesiology, University of Tsukuba
      Institute of Clinical Medicine, Tsukuba (Ibaraki, Japan). Diaphragmatic fatigue
      was induced in healthy, male, mongrel dogs by intermittent supramaximal bilateral
      electrophrenic stimulation at a low frequency (20 Hz) applied for 30 minutes.
      Immediately after the end of the fatigue-producing period, group 1 received
      inhaled vehicle only, group 2 received inhaled aminophylline 12.5 mg/mL, group 3
      received inhaled aminophylline 25 mg/mL, and group 4 was infused with verapamil
      0.1 mg/kg.min during inhalation of aminophylline 25 mg/mL. Diaphragmatic
      contractility was assessed using transdiaphragmatic pressure (Pdi). RESULTS:
      Twenty-eight dogs were used in the study (7 dogs were assigned to each treatment
      group). When fatigue was established, Pdi at low-frequency stimulation decreased
      significantly from baseline in all groups (all P<0.05), and no significant change
      in Pdi was found at high-frequency stimulation. In groups 2 and 3, during
      aminophylline inhalation, Pdi at 20-Hz stimulation increased significantly from
      fatigued values (both P<0.05). Pdi increased significantly more in group 3 than
      in group 2 (P<0.05). In group 4, infusion of verapamil offset the increase in Pdi
      seen with aerosolized aminophylline in fatigued diaphragm. The integrated
      electrical activity of the diaphragm did not change significantly in any group.
      CONCLUSIONS: Inhaled aminophylline significantly improved contractility of
      fatigued diaphragm in a dose-related manner in this experimental canine model
      (P<0.05). Its potent effect may be caused by transmembrane calcium movement.

PMID- 24944421
TI  - Unapproved prescriptions in two pediatric intensive care units in Israel.
AB  - BACKGROUND: Many medications prescribed to children worldwide have not been
      approved for pediatric use because the necessary clinical trials have not yet
      been performed. Children given these drugs have been shown to be at increased
      risk for adverse drug reactions. OBJECTIVE: The aim of this study was to assess
      the extent of unapproved (off label and/or unlicensed) use of medications in
      pediatric intensive care units (PICUs) in Israel. METHODS: Medications
      administered to patients treated in the PICUs of Soroka University Medical Center
      (SMC) and Assaf Harofe Medical Center (AHMC) were reviewed. Analyses were
      retrospective at SMC and prospective at AHMC. RESULTS: The records of 158
      patients were included in the study-116 patients at SMC (73.4%; 62 boys, 54
      girls; mean [SD] age, 38.9 [50.4] months) and 42 at AHMC (26.6%; 26 boys, 16
      girls; mean [SD] age, 63.3 [69.3] months). They received a total of 123 different
      medications. Sedatives and antibiotics were the most frequently prescribed drug
      classes at SMC (15.2% and 6.5%, respectively), and antibiotics, acetaminophen,
      and antiasthmatic drugs were most frequently prescribed at AHMC (14.4%, 13.6%,
      and 6.8%, respectively). Sympathomimetic drugs, sedatives, and antibiotics were
      the drugs most commonly prescribed in an unlicensed or off-label manner at SMC
      (11.4%, 11.4%, and 6.5%, respectively); at AHMC, they were antiinfectives,
      sympathomimetics, antiasthmatic drugs, and acetaminophen (18.7%, 16.9%, 12.7%,
      6.8%, respectively). The percentage of patients receiving unapproved medications
      (SMC, 93 [80.2%]; AHMC, 38 [90.5%]) and the percentage of unlicensed and off
      label prescriptions (SMC, 243 [41.5%]; AHMC, 118 [41.0%], respectively) were
      similar between the 2 PICUs. Inappropriate age was the most common off-label
      category, followed by different dose, different indication, and different route.
      CONCLUSION: The results of this study of unapproved prescriptions in 2 PICUs in
      Israel show a high number of such prescriptions and indicate an urgent need to
      investigate the use of those medications in children.

PMID- 24944422
TI  - Digoxin concentration in saliva and plasma in infants, children, and adolescents
      with heart disease.
AB  - BACKGROUND: Because of its narrow therapeutic index, therapeutic monitoring of
      digoxin is important in the management of infants and children receiving the drug
      for cardiac failure or arrhythmias, or following accidental ingestion. Whether
      saliva can replace plasma in the therapeutic monitoring of digoxin therapy in
      children is unclear. OBJECTIVE: This study assessed the value of determining
      saliva digoxin concentration in infants, children, and adolescents. METHODS:
      Infants, children, and adolescents receiving digoxin for various indications,
      whose digoxin dosage had remained unchanged for >=10 days, and whose compliance
      was good according to the parents were enrolled. Digoxin concentration was
      measured in paired specimens of citric acid-stimulated mixed saliva and plasma
      obtained simultaneously. RESULTS: Eighteen children (10 boys, 8 girls; mean [SD]
      age, 42.3 [53.1] months [range, 2 months-14 years]) were included in the study.
      Digoxin therapy was administered for cardiac failure due to dilated
      cardiomyopathy in 9 patients (50.0%), ventricular septal defect in 4 (22.2%),
      supraventricular tachycardia in 3 (16.7%), and after cardiac surgery in 2
      (11.1%). Digoxin concentration in the 20 paired specimens obtained varied from
      0.0 to 0.92 ng/mL (mean [SD], 0.25 [0.26] ng/mL) in saliva and from 0.27 to 1.54
      ng/mL (mean [SD], 0.77 [0.40] ng/mL) in plasma. The mean plasma/saliva digoxin
      concentration ratio was 2.8. CONCLUSIONS: This study of infants, children, and
      adolescents receiving digoxin for a variety of indications and whose dose was
      unchanged for >=10 days showed that marked individual variability in the
      saliva/plasma concentration ratio precludes the use of saliva in predicting the
      plasma digoxin concentration. The value of saliva digoxin (as opposed to plasma
      digoxin) measurements in the assessment of the cardiac effects of the drug in
      children remains to be determined.

PMID- 24944423
TI  - The Coincidental finding: has it happened again?

PMID- 24944424
TI  - Influenza prophylaxis in the long-term care facility: a case-control study of the
      risk factors for adverse drug reactions to amantadine.
AB  - BACKGROUND: Amantadine hydrochloride remains an inexpensive means of influenza A
      prophylaxis, but it is reported to have a high incidence of adverse drug
      reactions (ADRs) in residents of long-term care facilities (LTCFs) compared with
      newer, more expensive drugs. OBJECTIVE: This study attempted to determine the
      effects of poor renal function on the rate of ADRs and any other variables on the
      tolerability of prophylaxis in this population. This would allow a high-risk
      subset of LTCF residents to be identified before prophylaxis, thus decreasing the
      risk for ADRs from amantadine. METHODS: In this retrospective case-control study,
      a course of standardized low-dose (100-mg/d tablets) amantadine prophylaxis was
      ordered for all 242 residents of Ten Broeck Commons LTCF in Lake Katrine, New
      York, without influenza A for 14 days. Chart data of residents who developed ADRs
      (ADR group) were compared with those of a selected group who did not (control
      group). Residents' age, sex, renal function (blood urea nitrogen, serum
      creatinine, and creatinine clearance), dementia diagnosis, and number and classes
      of medications were compared. RESULTS: The ADR group comprised 25 residents (21
      women, 4 men; mean [SD] age, 84.8 [8.4] years); the control group, 29 residents
      (23 women, 6 men; mean [SD] age, 85.7 [7.5] years). The development of ADRs was
      not associated with differences in age, sex, renal function, or any medical
      condition, including measured, preexisting mental status changes between the
      groups. The overall risk for ADRs in the 242 residents was highest between days 8
      and 14 of prophylaxis (17 residents [7.0%]) compared with the first 7 days (8
      residents [3.3%]). Acute confusion was the most common ADR. All ADRs resolved on
      cessation of treatment. CONCLUSIONS: No preexisting medical condition was
      statistically associated with an increased risk for ADRs, but an association with
      the number of days of prophylaxis was observed. By shortening prophylaxis to 7
      days, the ADR risk may be lowered to be commensurate with more expensive
      medications.

PMID- 24944427
TI  - Single-dose azithromycin for acute otitis media: a
      pharmacokinetic/pharmacodynamic rationale.
AB  - The pharmacokinetic (PK) and pharmacodynamic (PD) properties of the azalide
      azithromycin distinguish it from other antibiotics. The PK profile of
      azithromycin features high tissue-to-serum ratios, including high concentrations
      in the middle ear, and a prolonged elimination half-life. These characteristics
      result from the accumulation of drug within cells and its subsequent slow,
      sustained release from cells and tissues into the bloodstream. The PD properties
      of azithromycin include bactericidal activity against key respiratory tract
      pathogens and a prolonged postantibiotic, or persistent, effect. In addition,
      white blood cells deliver the drug to infected foci, thereby enhancing local
      tissue concentrations and improving in vivo efficacy. Recent PK studies in mice
      suggest that a single, large dose of azithromycin achieves higher tissue
      concentrations than do multidose regimens. Other studies in animal infection
      models, in particular, a gerbil model of acute otitis media, have demonstrated
      improved bacterial eradication when azithromycin is administered as a single dose
      rather than divided over 2 or 3 days. Taken together, the results from these
      preclinical studies provide a PK/PD rationale for the use of single-dose
      azithromycin in the treatment of acute otitis media. Clinical data on the
      efficacy and safety of single-dose azithromycin for the treatment of acute otitis
      media in children are presented in 2 accompanying articles in this supplement. 

PMID- 24944429
TI  - RF-MEMS Load Sensors with Enhanced Q-factor and Sensitivity in a Suspended
      Architecture.
AB  - In this paper, we present and demonstrate RF-MEMS load sensors designed and
      fabricated in a suspended architecture that increases their quality-factor (Q
      factor), accompanied with an increased resonance frequency shift under load. The
      suspended architecture is obtained by removing silicon under the sensor. We
      compare two sensors that consist of 195 MUm * 195 MUm resonators, where all of
      the resonator features are of equal dimensions, but one's substrate is partially
      removed (suspended architecture) and the other's is not (planar architecture).
      The single suspended device has a resonance of 15.18 GHz with 102.06 Q-factor
      whereas the single planar device has the resonance at 15.01 GHz and an associated
      Q-factor of 93.81. For the single planar device, we measured a resonance
      frequency shift of 430 MHz with 3920 N of applied load, while we achieved a 780
      MHz frequency shift in the single suspended device. In the planar triplet
      configuration (with three devices placed side by side on the same chip, with the
      two outmost ones serving as the receiver and the transmitter), we observed a 220
      MHz frequency shift with 3920 N of applied load while we obtained a 340 MHz
      frequency shift in the suspended triplet device with 3920 N load applied. Thus,
      the single planar device exhibited a sensitivity level of 0.1097 MHz/N while the
      single suspended device led to an improved sensitivity of 0.1990 MHz/N.
      Similarly, with the planar triplet device having a sensitivity of 0.0561 MHz/N,
      the suspended triplet device yielded an enhanced sensitivity of 0.0867 MHz/N.

PMID- 24944428
TI  - Molecular genetic contributions to socioeconomic status and intelligence.
AB  - Education, socioeconomic status, and intelligence are commonly used as predictors
      of health outcomes, social environment, and mortality. Education and
      socioeconomic status are typically viewed as environmental variables although
      both correlate with intelligence, which has a substantial genetic basis. Using
      data from 6815 unrelated subjects from the Generation Scotland study, we examined
      the genetic contributions to these variables and their genetic correlations.
      Subjects underwent genome-wide testing for common single nucleotide polymorphisms
      (SNPs). DNA-derived heritability estimates and genetic correlations were
      calculated using the 'Genome-wide Complex Trait Analyses' (GCTA) procedures. 21%
      of the variation in education, 18% of the variation in socioeconomic status, and
      29% of the variation in general cognitive ability was explained by variation in
      common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and
      socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26
      (0.16), respectively. There are genetic contributions to intelligence and
      education with near-complete overlap between common additive SNP effects on these
      traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are
      also associated with the genetic foundations of intelligence. The results are
      also compatible with substantial environmental contributions to socioeconomic
      status.

PMID- 24944430
TI  - One Adult Who Is Crazy about You: Can Natural Mentoring Relationships Increase
      Assets among Young Adults With and Without Foster Care Experience?
AB  - During emerging adulthood, most youth receive family support to help them weather
      the difficulties associated with transitioning to independence. When foster youth
      emancipate, they confront the challenges associated with emerging adulthood, and
      are at risk of having to transition without family support. Many are in danger of
      failing to meet minimal levels of self-sufficiency. A caring adult who offers
      social support is normative for adolescent development and protective for youth
      across many risk conditions. Natural mentoring can cultivate such relationships.
      This study examines the association between natural mentor relationship
      characteristics, and material hardship and asset-related outcomes during the
      emerging adulthood period in both a normative sample of young adults and young
      adults identified as former foster youth. This study also considers the potential
      mediating effect of future expectations. Data from Wave 3 of the National
      Longitudinal Study of Adolescent Health that pertain to 15,197 respondents are
      used. Path models with categorical dependent variables were estimated using a
      Maximum Likelihood method with standard errors that are robust to non-normality
      and non-independence of observations. "Like a parent," "role model," and
      "guidance/advice" were significantly associated with assets among both groups.
      This study contributes to the growing body of literature on natural mentoring and
      former foster youth, and highlights the value of increasing our understanding of
      natural mentor roles for intervention development. The focus on assets-related
      outcomes is a novel approach to investigating the benefits of natural mentoring
      to the healthy development of youth. This paper is the first to consider the
      association between natural mentoring and assets building among both former and
      nonformer foster youth.

PMID- 24944431
TI  - Homeownership and parenting practices: Evidence from the community advantage
      panel.
AB  - This study examines whether there is a significant relationship between
      homeownership and engaged parenting practices among low- and moderate-income
      households. Using analytic methods which account for selection effects and
      clustering, we test whether homeownership can act as a protective factor against
      parental disengagement from children. Controlling for individual characteristics,
      analyses demonstrate that homeowners are more likely than renters to demonstrate
      engaged parenting behaviors such as organizing structured activities for their
      children. While renters are more likely to read to their children, the children
      of homeowners spend less time watching television and playing video games.
      Implications for low-income housing policy are discussed in light of these
      findings.

PMID- 24944432
TI  - Controlling female cancer in Argentina. Divergent initiatives and the road to
      fragmentation.
AB  - This article analyses the organisation of cancer control in Argentina, with a
      special focus on the initiatives, institutions, and models that targeted female
      or gynaecological cancers. It identifies and examines the main factors in the
      process of elaborating a national policy to control the disease drawing on a
      series of actors and instruments such as the state, medical professionals,
      institutions and services, and the use of technology (notably diagnostic tools)
      for the detection of the disease. It traces the developments in the organisation
      highlighting its transformations from a centralising to a decentralised model of
      service provision. Using the concept of "path-dependence" the article examines
      the continuities and changes observed in the organisation of female cancer
      critically signalling the particular time at which a path was taken where
      "fragmentation" became consolidated within the health system. It also argues that
      it was within the field of cancer diagnosis that Argentinian doctors first sought
      to create the foundational structures of cancer organisation. The article
      contends that the path-dependence analytical approach helps us acknowledge the
      importance of historical analysis in the identification of factors that led to
      the lack of service coordination, including the persistent strain between
      national/provincial states that hampered the development of comprehensive
      programmes, aspects that have continued to mark efforts in the elaboration of
      cancer policies to the present day.

PMID- 24944433
TI  - Reducing STD/HIV stigmatizing attitudes through community popular opinion leaders
      in Chinese markets.
AB  - Reducing STDs and HIV/AIDS incidence requires campaigns designed to change
      knowledge, attitudes and practices of risky sexual behavior and its consequences.
      In China, a significant obstacle to such changes is the stigma associated with
      these diseases. Thus one campaign intervention strategy is to train credible
      community popular opinion leaders to discuss these issues in everyday social
      venues. This study tested the effectiveness of such an approach on reducing
      HIV/AIDS stigma, across two years, from a sample of over 4500 market vendors, in
      three conditions. Results showed an increasing growth in market communication
      about intervention messages, and concomitant declines in stigmatizing attitudes,
      across time, with the greatest changes in community popular opinion leaders,
      significant changes in intervention non-opinion leaders, and little change in the
      control markets.

PMID- 24944434
TI  - Development of Bench and Full-Scale Temperature and pH Responsive Functionalized
      PVDF Membranes with Tunable Properties.
AB  - Temperature and pH responsive polymers (poly(N-isopropylacrylamide) (PNIPAAm),
      and polyacrylic acid, PAA) were synthesized in one common macrofiltration PVDF
      membrane platform by pore-filling method. The microstructure and morphology of
      the PNIPAAm-PVDF, and PNIPAAm-FPAA-PVDF membranes were studied by attenuated
      total reflectance Fourier transform infrared (ATR-FTIR), thermogravimetric
      analysis (TGA), scanning electron microscopy (SEM) and atomic force microscopy
      (AFM). The membrane pore size was controlled by the swelling and shrinking of the
      PNIPAAm at the temperature around lower critical solution temperature (LCST). The
      composite membrane demonstrated a rapid and reversible swelling and deswelling
      change within a small temperature range. The controllable flux makes it possible
      to utilize this temperature responsive membrane as a valve to regulate filtration
      properties by temperature change. Dextran solution (Mw=2,000,000g/mol, 26 nm
      diameter) was used to evaluate the separation performance of the temperature
      responsive membranes. The ranges of dextran rejection are from 4% to 95%
      depending on the temperature, monomer amount and pressure. The full-scale
      membrane was also developed to confirm the feasibility of our bench-scale
      experimental results. The full-scale membrane also exhibited both temperature and
      pH responsivity. This system was also used for controlled nanoparticles synthesis
      and for dechlorination reaction.

PMID- 24944435
TI  - Modelling the evolution of a bi-partite network Peer referral in interlocking
      directorates.
AB  - A central part of relational ties between social actors are constituted by shared
      affiliations and events. The action of joint participation reinforces personal
      ties between social actors as well as mutually shared values and norms that in
      turn perpetuate the patterns of social action that define groups. Therefore the
      study of bipartite networks is central to social science. Furthermore, the
      dynamics of these processes suggests that bipartite networks should not be
      considered static structures but rather be studied over time. In order to model
      the evolution of bipartite networks empirically we introduce a class of models
      and a Bayesian inference scheme that extends previous stochastic actor-oriented
      models for unimodal graphs. Contemporary research on interlocking directorates
      provides an area of research in which it seems reasonable to apply the model.
      Specifically, we address the question of how tie formation, i.e. director
      recruitment, contributes to the structural properties of the interlocking
      directorate network. For boards of directors on the Stockholm stock exchange we
      propose that a prolific mechanism in tie formation is that of peer referral. The
      results indicate that such a mechanism is present, generating multiple interlocks
      between boards.

PMID- 24944438
TI  - From the President's desk.

PMID- 24944437
TI  - THE CRIMINAL PSYCHOPATH: HISTORY, NEUROSCIENCE, TREATMENT, AND ECONOMICS.
AB  - The manuscript surveys the history of psychopathic personality, from its origins
      in psychiatric folklore to its modern assessment in the forensic arena.
      Individuals with psychopathic personality, or psychopaths, have a
      disproportionate impact on the criminal justice system. Psychopaths are twenty to
      twenty-five times more likely than non-psychopaths to be in prison, four to eight
      times more likely to violently recidivate compared to non-psychopaths, and are
      resistant to most forms of treatment. This article presents the most current
      clinical efforts and neuroscience research in the field of psychopathy. Given
      psychopathy's enormous impact on society in general and on the criminal justice
      system in particular, there are significant benefits to increasing awareness of
      the condition. This review also highlights a recent, compelling and cost
      effective treatment program that has shown a significant reduction in violent
      recidivism in youth on a putative trajectory to psychopathic personality.

PMID- 24944436
TI  - Increasing Positive Outlook Partially Mediates the Effect of Empirically
      Supported Treatments on Depression Symptoms Among Adolescents.
AB  - Among adolescents there is evidence that cognitive change partially mediates the
      effect of cognitive behavioral therapy (CBT) on depression outcome. However,
      prior studies have been limited by small samples, narrow measures of cognition,
      and failure to compare cognitive change following CBT to cognitive change
      following antidepressant medication. This study examined whether change in four
      cognitive constructs (cognitive distortions, cognitive avoidance, positive
      outlook, and solution-focused thinking) mediated change in depression severity in
      a sample of 291 adolescents who participated in the Treatment for Adolescents
      with Depression Study (TADS). TADS assessed the effects of CBT, fluoxetine, and
      their combination on depression severity. All three treatments were associated
      with change in the cognitive constructs and combination treatment produced the
      greatest change. Furthermore, change in the cognitive constructs partially
      mediated change in depression severity within all three treatments. Results
      implicated positive outlook as the construct most associated with change in
      depression severity over 36 weeks.

PMID- 24944439
TI  - Influence of calcium hydroxide on the post-treatment pain in Endodontics: A
      systematic review.
AB  - INTRODUCTION: Pain of endodontic origin has been a major concern to the patients
      and the clinicians for many years. Post-operative pain is associated with
      inflammation in the periradicular tissues caused by irritants egressing from root
      canal during treatment. It has been suggested that calcium hydroxide intra-canal
      medicament has pain-preventive properties because of its anti-microbial or tissue
      altering effects. Some dispute this and reasoned that calcium hydroxide may
      initiate or increase pain by inducing or increasing inflammation. OBJECTIVE: To
      evaluate the effectiveness of calcium hydroxide in reducing the post-treatment
      pain when used as an intra-canal medicament. MATERIALS AND METHODS: THE FOLLOWING
      DATABASES WERE SEARCHED: PubMed CENTRAL (until July 2013), MEDLINE, and Cochrane
      Database of Systematic Reviews. Bibliographies of clinical studies and reviews
      identified in the electronic search were analyzed for studies published outside
      the electronically searched journals. The primary outcome measure was to evaluate
      the post-treatment pain reduction when calcium hydroxide is used as an intra
      canal medicament in patients undergoing root canal therapy. RESULTS: The reviews
      found some clinical evidence that calcium hydroxide is not very effective in
      reducing post-treatment pain when it is used alone, but its effectiveness can be
      increased when used in combination with other medicaments like chlorhexidine and
      camphorated monochlorophenol (CMCP). CONCLUSION: Even though calcium hydroxide is
      one of the most widely used intra-canal medicament due to its anti-microbial
      properties, there is no clear evidence of its effect on the post-treatment pain
      after the chemo-mechanical root canal preparation.

PMID- 24944440
TI  - Effect of calcium hydroxide and triple antibiotic paste as intracanal medicaments
      on the incidence of inter-appointment flare-up in diabetic patients: An in vivo
      study.
AB  - AIM: To evaluate and compare the effect of antibacterial intracanal medicaments
      on inter-appointment flare-up in diabetic patients. MATERIALS AND METHODS: Fifty
      diabetic patients requiring root canal treatment were assigned into groups I, II,
      and III. In group I, no intracanal medicament was placed. In groups II and III,
      calcium hydroxide and triple antibiotic pastes were placed as intracanal
      medicaments, respectively. Patients were instructed to record their pain on days
      1, 2, 3, 7, and 14. Inter-appointment flare-up was evaluated using verbal rating
      scale (VRS). RESULTS: Overall incidence of inter-appointment flare-up among
      diabetic patients was found to be 16%. In group I, 50% of the patients and in
      group II, 15% of the patients developed inter-appointment flare-up. However, no
      patients in group III developed inter-appointment flare-up. The comparison of
      these results was found to be statistically significant (P = 0.002; chi(2) =
      12.426). However, with respect to intergroup comparison, only the difference
      between groups I and III was found to be statistically significant (P = 0.002;
      chi(2) = 12.00). CONCLUSIONS: Calcium hydroxide and triple antibiotic paste are
      effective for managing inter-appointment flare-ups in diabetic patients. Triple
      antibiotic paste is more effective than calcium hydroxide in preventing the
      occurrence of flare-up in diabetic patients.

PMID- 24944441
TI  - Filling of simulated lateral canals with gutta percha or resilon when using
      thermomechanical compaction.
AB  - AIMS: To evaluate the filling of simulated lateral canals with gutta-percha or
      Resilon when using thermomechanical compaction. SETTING AND DESIGN: Forty-five
      human single-rooted teeth were subjected to tooth decalcification and clearing.
      MATERIALS AND METHODS: After root canal preparation, artificial lateral canals
      were made at 2, 5, and 8 mm from the working length (WL), corresponding to the
      apical, middle, and cervical thirds, respectively. The specimens were divided (n
      = 15) according to the filling material: Dentsply gutta-percha (GD), Odous gutta
      percha (GO), and Resilon cones (RE). Root canals were obturated by
      thermomechanical compaction using a #45 compactor and no sealer. Lateral canals
      were analyzed by digital radiography and digital images after tooth
      decalcification and clearing using the Image Tool software. STATISTICAL ANALYSIS
      USED: Data were subjected to the Kruskal-Wallis and Dunn tests at 5%
      significance. RESULTS: In the coronal third, RE and GO presented more filling
      ability than GD (P < 0.05). In the middle and apical thirds, RE presented the
      best results. CONCLUSIONS: Resilon demonstrated filling ability as material for
      root canal obturation by using thermomechanical compaction.

PMID- 24944442
TI  - Assessing microleakage of composite restorations in class V cavities prepared by
      Er:YAG laser irradiation or diamond bur.
AB  - INTRODUCTION: The aim of this study was to make a comparison between microleakage
      of conventionally restored class V cavities using bur and acid etchant and, the
      ones prepared and conditioned by Er:YAG laser. MATERIALS AND METHODS: 30 recently
      extracted intact caries and filling free human permanent molars were used for
      this study. Then, Cold cure acrylic resin was used to seal the apices. The
      samples were randomly assigned to 5 groups of six each. Class V cavities were
      prepared one on buccal and one on lingual surface of each sample. Group 1: cavity
      preparation by diamond bur and turbine + acid etch, Group 2: cavity preparation
      by Er:YAG laser + acid etch, Group 3: cavity preparation by Er:YAG laser + Laser
      etching, Group 4: cavity preparation by diamond bur and turbine + laser etching,
      Group 5: cavity preparation by Er:YAG laser with no conditioning procedure. The
      cavities restored with restorative composite resin. Samples were then immersed in
      2% methylene blue solution for 24 hours. The data were then analyzed using
      Wilcoxon signed ranks test and Kruskal-Wallis statistical tests. RESULTS: The
      Kruskal Wallis test showed a significant difference (P < 0.05) between enamel and
      cementum margin microleakage, while the higher microleakage was related to the
      cementum margin of restorations. CONCLUSION: There was no significant difference
      in evaluating microleakeage degree of cavities prepared by Er:YAG laser and
      diamond bur.

PMID- 24944443
TI  - Effect of ascorbic acid on bond strength between the hydrogen peroxide-treated
      fiber posts and composite resin cores.
AB  - AIM: This study evaluated the effect of 10% ascorbic acid on the bond strength
      between fiber post and composite resin core after applying 24% hydrogen peroxide.
      MATERIALS AND METHODS: Twenty-four hydrogen peroxide-treated fiber posts were
      divided into 4 groups (n = 6). Group 1 was the control group with no treatment.
      In groups 2-4, post surfaces were treated with 10% v ascorbic acid solution for
      10, 30 and 60 minutes, respectively. Cores were built up using flowable composite
      resin. Two sticks were prepared from each specimen. Microtensile bond strength
      test was performed for each stick. Failure modes of sticks were evaluated under a
      stereomicroscope (*20). Surface morphologies of two fractured sticks from each
      group were assessed by SEM. STATISTICAL ANALYSIS: Data were analyzed using one
      way ANOVA and Tukey HSD tests (alpha = 0.05). RESULTS: The highest microtensile
      bond strength was observed in Group 4 (20.55 +/- 2.09) and the lowest in Group 1
      (10.10 +/- 0.55). There were significant differences in microtensile bond
      strength between all the groups (P < 0.05). CONCLUSION: It is concluded that
      ascorbic acid application increased the microtensile bond strength between the
      hydrogen peroxide treated fiber post and composite resin core. The increase is
      dependent on the duration of exposure to the antioxidant.

PMID- 24944444
TI  - Comparison of periapical radiography with cone beam computed tomography in the
      diagnosis of vertical root fractures in teeth with metallic post.
AB  - AIM: To compare the diagnostic accuracy of conventional periapical radiography
      and cone beam computed tomography (CBCT) in detecting vertical root fracture
      (VRF) in tooth with metallic post (MP). MATERIALS AND METHODS: Twenty
      endodontically-treated teeth received MPs, artificial fractures were created in
      10 teeth, and they were all examined with tomography and radiography. The sample
      consisted of periapical radiography with post and without post, and tomography
      with post and without post; each group with five fractured and five non-fractured
      teeth. The images were evaluated by three dental/maxillofacial radiologists and
      statistical validations were carried out using receiver operating characteristic
      (ROC) analysis. RESULTS: Sensitivity and specificity of the area under the ROC
      (Az) of tomography with post (Az = 0.953) and without post (Az = 0.956) were
      significantly higher than those of periapical radiography with post (Az = 0.753)
      and without post (Az = 0.778). CONCLUSION: CBCT was more accurate than
      conventional periapical radiography in detecting VRF.

PMID- 24944445
TI  - An in vitro comparative evaluation of physical properties of four different types
      of core materials.
AB  - INTRODUCTION: Compressive and tensile stresses of core materials are important
      properties because cores usually replace a large bulk of tooth structure and must
      resist multidirectional masticatory forces for many years. MATERIAL AND METHODS:
      The present study was undertaken to find out the best core build up material with
      respect to their physical properties among resin-based composites. Individual
      compressive, tensile, and flexural strength of fiber-reinforced dual cure resin
      core build up material, silorane-based composite resin, and dual curing composite
      for core build up with silver amalgam core was used as control were evaluated and
      compared using universal testing machine. Data were statistical analysed using
      Kruskal-Wallis test to determine whether statistically significant differences (P
      < 0.05) existed among core materials. Both dual cure composite materials with
      nanofillers were found superior to amalgam core. The silorane-based material
      showed the highest flexural strength, but other mechanical properties were
      inferior to dual cure composite materials with nanofillers.

PMID- 24944447
TI  - Analysis of C-shaped canal systems in mandibular second molars using surgical
      operating microscope and cone beam computed tomography: A clinical approach.
AB  - AIMS: The study was aimed to acquire better understanding of C-shaped canal
      systems in mandibular second molar teeth through a clinical approach using
      sophisticated techniques such as surgical operating microscope and cone beam
      computed tomography (CBCT). MATERIALS AND METHODS: A total of 42 extracted
      mandibular second molar teeth with fused roots and longitudinal grooves were
      collected randomly from native Indian population. Pulp chamber floors of all
      specimens were examined under surgical operating microscope and classified into
      four types (Min's method). Subsequently, samples were subjected to CBCT scan
      after insertion of K-files size #10 or 15 into each canal orifice and evaluated
      using the cross-sectional and 3-dimensional images in consultation with dental
      radiologist so as to obtain more accurate results. Minimum distance between the
      external root surface on the groove and initial file placed in the canal was also
      measured at different levels and statistically analyzed. RESULTS: Out of 42
      teeth, maximum number of samples (15) belonged to Type-II category. A total of
      100 files were inserted in 86 orifices of various types of specimens. Evaluation
      of the CBCT scan images of the teeth revealed that a total of 21 canals were
      missing completely or partially at different levels. The mean values for the
      minimum thickness were highest at coronal followed by middle and apical third
      levels in all the categories. Lowest values were obtained for teeth with Type-III
      category at all three levels. CONCLUSIONS: The present study revealed anatomical
      variations of C-shaped canal system in mandibular second molars. The prognosis of
      such complex canal anatomies can be improved by simultaneous employment of modern
      techniques such as surgical operating microscope and CBCT.

PMID- 24944446
TI  - Intraorifice sealing ability of different materials in endodontically treated
      teeth: An in vitro study.
AB  - BACKGROUND: Microbial contamination of the pulp space is one of the major factors
      associated with endodontic failure. Thus, in addition to a three dimentional
      apical filling a coronal seal for root canal fillings has been recommended. AIM:
      The present study was conducted to evaluate and compare the intra-orifice sealing
      ability of three experimental materials after obturation of the root canal
      system. MATERIALS AND METHODS: Fourty single rooted mandibular premolars were
      decoronated, cleaned, shaped and obturated. Gutta-percha was removed to the depth
      of 3.5 mm from the orifice with a heated plugger. Ten specimens each were sealed
      with Light Cure Glass Ionomer Cement (LCGIC), Flowable Composite (Tetric N-Flow),
      and Light Cure Glass Ionomer Cement with Flowable Composite in Sandwich Technique
      along with a positive control respectively and roots submerged in Rhodamine-B dye
      in vacuum for one week. Specimens were longitudinally sectioned and leakage
      measured using a 10X stereomicroscope and graded for depth of leakage. RESULTS:
      According to the results of the present study LC GIC + Tetric N Flow demonstrated
      significantly better seal (P < 0.01) than LC GIC. However there was no
      statistically significant difference in leakage (P > 0.01) between Tetric N-Flow
      and LCGIC+Tetric N-Flow groups. CONCLUSION: In the current study LCGIC+Tetric N
      Flow was found to be superior over other experimental materials as intra-orifice
      barriers.

PMID- 24944448
TI  - The effect of casein phosphopeptide-amorphous calcium phosphate paste and sodium
      fluoride mouthwash on the prevention of dentine erosion: An in vitro study.
AB  - AIM: The purpose was to compare the effect of 0.2% sodium fluoride mouthwash and
      casein phosphopeptide-amorphous calcium phosphate paste on prevention of dentin
      erosion. MATERIALS AND METHODS: Buccal surfaces of 36 sound premolar teeth were
      ground flat and polished with abrasive discs. Half the polished surfaces were
      covered with tape to maintain a reference surface. Samples were randomly
      allocated into three groups. Group A was pretreated with tooth mousse (TM) 4
      times a day for 5 days. Group B was pretreated with 0.2% sodium fluoride
      mouthwash 4 times a day for 5 days. Group C was considered as the control group
      with no pretreatment. In the next step, the samples were exposed to Coca-Cola 4
      times a day for 3 days. After each erosive cycle, the samples were rinsed with
      deionized water and stored in artificial saliva. The surface loss was determined
      using profilometry. RESULTS: The erosion in both Groups A and B was less than the
      control group. The surface loss in mouthwash group was significantly lower than
      in the control group. Erosion in TM group was more than the mouthwash group and
      less than the control group. CONCLUSION: Sodium fluoride mouthwash is more
      effective for prevention of dentin erosion.

PMID- 24944449
TI  - Cyclic fatigue resistance of OneShape, Reciproc, and WaveOne: An in vitro
      comparative study.
AB  - AIMS: The aim of this in vitro study was to evaluate the cyclic fatigue
      resistance of three single-use nickel-titanium (NiTi) instruments. MATERIALS AND
      METHODS: Forty files each of OneShape (OS), Reciproc R25 (R25), WaveOne Primary
      (WO) file, and ProTaper (PT) F2 (as control) were tested in four curved
      artificial canals with different angles and radii of curvature. The number of
      cycles to fracture (NCF) was determined and the data were compared for
      differences by using two-way analysis of variance (P < 0.05). RESULTS: In
      general, all single-use instruments were more resistant than traditional rotary
      instrument used as control. R25 showed the highest cyclic fatigue resistance. One
      Shape and WO files showed similar cyclic fatigue resistance values, higher than
      PT F2. CONCLUSIONS: Within the limitations of this study, it can be concluded
      that R25 was the most fatigue resistant. OS rotary instruments seem to have good
      mechanical resistance, similar to NiTi files developed for reciprocating motion.

PMID- 24944450
TI  - Influence of cement type and thickness on polyfiber post adhesion.
AB  - INTRODUCTION: To evaluate the effect of two different post space diameters and
      related resin cement film thicknesses on the bond strength of a polyfiber post.
      MATERIALS AND METHODS: A total of 48 premolars were randomly divided into two
      according to the post space diameter: 1.1 mm and 1.5 mm. Then each group was
      divided into three sub-groups according to luting cement used: RelyX U100,
      Panavia F2.0/ED primer, Clearfil SA cement. Spirapost was then luted into the
      canal using luting cements. Two slices were obtained from each root specimen.
      Push-out tests were performed. Data was analyzed with Kruskal-Wallis and Connover
      post-hoc and Mann-Whitney U-test (P < 0.05). RESULTS: Push-out bond strength was
      found to vary significantly according to type of adhesive system and post space
      diameter size (P < 0.05). The self-adhesive resin cement RelyX U100 had
      significantly higher bond strengths compared with the other adhesive system (P <
      0.05). The self-etch adhesive system (Panavia F2.0) showed significantly lower
      bond strengths compared with the other systems (P < 0.05). There was a
      significant interaction between the luting systems and post space diameter (P <
      0.05). CONCLUSION: The increases in post space diameter significantly reduced the
      bond strength of Spirapost to root dentine for both groups.

PMID- 24944451
TI  - The effect of different beverages on surface hardness of nanohybrid resin
      composite and giomer.
AB  - AIMS: To investigate the effects of five beverages (apple cider, orange juice,
      Coca-Cola, coffee, and beer) on microhardness and surface characteristic changes
      of nanohybrid resin composite and giomer. MATERIALS AND METHODS: Ninety-three
      specimens of each resin composite and giomer were prepared. Before immersion,
      baseline data of Vicker's microhardness was recorded and surface characteristics
      were examined using scanning electron microscopy (SEM). Five groups of discs (n =
      18) were alternately immersed in 25 mL of each beverage for 5 s and in 25 mL of
      artificial saliva for 5 s for 10 cycles. Specimens were then stored in artificial
      saliva for 24 h. This process was repeated for 28 days. After immersion,
      specimens were evaluated and data were analyzed by two-way repeated analysis of
      variance (ANOVA), Tukey's honestly significant difference (HSD), and a t-test
      (alpha = 0.05). RESULTS: Microhardness of all groups significantly decreased
      after being immersed in the tested beverages (P < 0.05). SEM photomicrographs
      presented surface degradation of all groups. CONCLUSIONS: The effect of these
      beverages on the surface of both restorative materials also depended upon the
      exposure time and chemical composition of the restorative materials and
      beverages.

PMID- 24944452
TI  - Comparative evaluation of antibacterial activity of total-etch and self-etch
      adhesive systems: An ex vitro study.
AB  - AIM: The aim of this ex vivo study was to compare the antibacterial activity of
      total-etch and self-etch adhesive systems against Streptococcus mutans,
      Lactobacillus acidophilus, and Actinomyces viscosus through disk diffusion
      method. MATERIALS AND METHODS: The antibacterial effects of Single Bond (SB) and
      Adper Prompt (AP) and aqueous solution of chlorhexidine 0.2% (positive control)
      were tested against standard strain of S. mutans, L. acidophilus, and A. viscosus
      using the disk diffusion method. The diameters of inhibition zones were measured
      in millimeters. Data was analyzed using Kruskal-Wallis test. Mann-Whitney U test
      was used for pairwise comparison. RESULT: Of all the materials tested, AP showed
      the maximum inhibitory action against S. mutans and L. acidophilus. Aqueous
      solution of chlorhexidine 0.2% showed the maximum inhibitory action against A.
      viscosus. Very minimal antibacterial effect was noted for SB. CONCLUSION: The
      antibacterial effects observed for the tested different dentin bonding systems
      may be related to the acidic nature of the materials.

PMID- 24944453
TI  - Effect of addition of 2% chlorhexidine or 10% doxycycline on antimicrobial
      activity of biodentine.
AB  - AIM: The purpose of this in vitro study was to determine whether the addition of
      2% chlorhexidine gluconate or 10% doxycycline would enhance the antimicrobial
      activity of Biodentine against Staphylococcus aureus (ATCC-25923), Enterococcus
      faecalis (ATCC-29212), Candida albicans (ATCC-90028), and Streptococcus mutans
      (MTCC-497). MATERIALS AND METHODS: Three wells of 4 mm diameter and 4 mm depth on
      each plate were prepared on the agar medium with standardized suspensions of each
      microorganism. Biodentine powder mixed with 2% chlorhexidine (0.06 g) or 10%
      doxycycline (0.30 g) in its liquid or liquid alone was placed to fill each well.
      Plates were incubated at 37 degrees C as required for microbial growth. A
      blinded, independent observer measured zones of inhibition. The data were
      analyzed using independent "t" test to compare the differences among the three
      cement preparations for different micro-organisms. RESULTS: All Biodentine
      samples inhibited microbial growth. The highest mean diameters of zone of
      inhibition for all the micro-organisms were found around Biodentine/chlorhexidine
      (13.417) followed by Biodentine alone (12.236) and Biodentine/doxycycline
      (11.25). CONCLUSION: In conclusion, adding 2% chlorhexidine gluconate in liquid
      of Biodentine enhanced the antimicrobial activity of Biodentine against all the
      tested micro-organisms except Candida albicans, while addition of 10% doxycycline
      decreased the antimicrobial activity of Biodentine. The differences were
      significant statistically (P < 0.05).

PMID- 24944454
TI  - Evaluation of antifungal activity of white-colored mineral trioxide aggregate on
      different strains of Candida albicans in vitro.
AB  - AIM: The purpose of this study was to evaluate the antifungal action of various
      concentrations of white mineral trioxide aggregate (MTA) against seven different
      strains of Candida albicans using the tube dilution test. MATERIALS AND METHODS:
      Fresh mix of MTA was prepared at concentrations of 100, 50, 25, and 12.5 mg/ml
      and added to a broth tube containing Sabouraud's liquid medium. A total of 1287
      broth tubes were prepared and divided into experimental and control groups. Stock
      cultures of seven strains of C. albicans were obtained. Fresh inoculate of the
      microorganism was prepared by growing overnight cultures. Aliquots of the test C.
      albicans were taken and added to the test tubes. All tubes were incubated at 37
      degrees C for 1-, 24-, 72-, and 168-h time periods. At each time period, the
      presence of C. albicans colonies was assessed. STATISTICAL ANALYSIS USED:
      Differences among the groups were statistically analyzed using Kruskal-Wallis and
      Mann-Whitney U tests. RESULTS: Results showed that one strain showed resistance
      even after 3 days at the lower MTA concentrations of 12.5 and 25 mg/ml. Growth
      reoccurred with three strains at MTA concentration of 12.5 mg/ml after 7 days. A
      significant difference was found between strain 3 and other strains at MTA
      concentrations of 12.5 and 25 mg/ml at the 3-days time period and between tubes
      containing 12.5 mg/ml and tubes containing higher concentrations of MTA at the 7
      days time period. CONCLUSION: White MTA in concentrations of 100 and 50 mg/ml is
      effective in inhibiting the seven tested strains of C. albicans for periods up to
      1 week.

PMID- 24944455
TI  - An in vitro evaluation of effect of eugenol exposure time on the shear bond
      strength of two-step and one-step self-etching adhesives to dentin.
AB  - OBJECTIVES: To evaluate the effect of the eugenol exposure time of an eugenol
      based provisional restorative material on the shear bond strength of two-step and
      one-step self-etching adhesives to dentin, at three different time intervals of
      24 h, 7 days, and 14 days. MATERIALS AND METHODS: Forty extracted human posterior
      teeth were sectioned mesiodistally to obtain two halves and the resulting 80
      halves were randomly assigned into four groups of 20 specimens each (Group-I, 
      II, -III, and -IV). Cavities of specified dimensions were prepared to expose
      dentin surface. In Group-I, temporarization was carried out with noneugenol
      cement (Orafil-G) for 24 h (control group). In Group-II, -III, and -IV,
      temporarization was carried out with eugenol cement (intermediate restorative
      material (IRM)) for 24 h, 7 days, and 14 days, respectively. Each group was
      further divided into two subgroups of 10 teeth each for two-step (Adper SE Plus)
      and one-step (Adper Easy One) self-etch adhesive systems, respectively. A plastic
      tube loaded with microhybrid composite resin (Filtek Z-350, 3M) was placed over
      the dentin surface and light cured. The specimens were subjected to shear stress
      in universal testing machine. RESULTS: Group-II yielded low shear bond strength
      values compared with Group-III, -IV, and Group-I, which was statistically
      significant. CONCLUSIONS: The prior use of eugenol containing temporary
      restorative material reduced the bond strength of self-etch adhesive systems at
      24-h period. No reduction in bond strength at 7 or 14 days exposure was observed
      with either two-step or one-step self-etch adhesive.

PMID- 24944456
TI  - Cone beam-computed topographic evaluation of a central incisor with an open apex
      and a failed root canal treatment using one-step apexification with BiodentineTM:
      A case report.
AB  - A symptomatic endodontically treated immature tooth with periapical pathology
      presents multiple challenges to the clinician. Owing to incomplete root
      formation, gutta percha removal has to be done carefully without further damaging
      the periapical tissue or pushing the obturating material beyond the apex.
      Nonsurgical approach toward treating such a tooth would necessitate the creation
      of an apical barrier followed by conventional root canal treatment. Current
      literature suggests one-step apexification with mineral trioxide aggregate (MTA),
      with an apical matrix as the treatment of choice. A new calcium silicate-based
      cement also called as dentine substitute by the manufacturers with good handling
      properties has been introduced recently by the trade name BiodentineTM
      (Septodont, St. Maurdes Fosses, France). This case report presents management of
      a secondary endodontic case with an open apex treated with the concept of 'lesion
      sterilization and tissue repair (LSTR)' using triantibiotic paste and
      BiodentineTM for apical barrier formation. A 12-month follow up with cone beam
      computed topography (CBCT) exhibited progressive involution of periapical
      radiolucency with indications of good healing of the periapical tissues and
      absence of clinical symptoms. 

PMID- 24944457
TI  - Root canal treatment of a maxillary second premolar with two palatal roots: A
      case report.
AB  - Anatomical variations in root canal morphology are an enigma and it is this
      variability, which is often a complicating factor in a successful root canal
      treatment. To achieve success in endodontic therapy it is imperative that all the
      canals are located, cleaned and shaped and obturated three dimensionally.
      Maxillary first premolar having three separate roots has an incidence of 0.5-6%.
      Even rarer are reported clinical case reports of maxillary second premolar with
      three separate roots and three canals. This case report describes the endodontic
      management of maxillary second premolar with two palatal roots and one buccal
      root having three root canals. 

PMID- 24944458
TI  - Management of geminated maxillary lateral incisor using cone beam computed
      tomography as a diagnostic tool.
AB  - Geminated teeth are consequences of developmental anomalies leading to joined
      elements, due to incomplete attempt of one tooth germ to divide into two. This
      case report describes successful endodontic treatment of an unaesthetic geminated
      permanent maxillary lateral incisor tooth and its esthetic rehabilitation using
      all ceramic crowns. Newer imaging technique like cone beam computed tomography
      was taken for the better understanding of the complicated root canal morphology. 

PMID- 24944459
TI  - An innovative approach in microscopic endodontics.
AB  - The introduction of the dental operating microscope was a turning point in the
      history of dentistry. It triggered a rapid transition from the conventional world
      of macro-dentistry to the precise, detailed world of micro-dentistry. However,
      working at these higher-power magnifications brings the clinician into the realm
      where even slight hand movements are disruptive. Physiologic hand tremor is a
      problem resulting in difficulty in mouth mirror placement. Hence, in this paper,
      a new instrument was designed to overcome the drawback of hand tremors during
      microscopic endodontics. 

PMID- 24944460
TI  - Endodontics simplified and basics of biostatistics.

PMID- 24944461
TI  - Disparate Changes in the Mechanical Properties of Murine Carotid Arteries and
      Aorta in Response to Chronic Infusion of Angiotensin-II.
AB  - Chronic infusion of angiotensin-II has proved useful for generating dissecting
      aortic aneurysms in atheroprone mice. These lesions preferentially form in the
      suprarenal abdominal aorta and sometimes in the ascending aorta, but reasons for
      such localization remain unknown. This study focused on why these lesions do not
      form in other large (central) arteries. Toward this end, we quantified and
      compared the geometry, composition, and biaxial material behavior (using a
      nonlinear constitutive relation) of common carotid arteries from three groups of
      mice: non-treated controls as well as mice receiving a subcutaneous infusion of
      angiotensin-II for 28 days that either did or did not lead to the development of
      a dissecting aortic aneurysm. Consistent with the mild hypertension induced by
      the angiotensin-II, the carotid wall thickened as expected and remodeled
      modestly. There was no evidence, however, of a marked loss of elastic fibers or
      smooth muscle cells, each of which appear to be initiating events for the
      development of aneurysms, and there was no evidence of intramural discontinuities
      that might give rise to dissections.

PMID- 24944462
TI  - Hepatitis C virus core antigen testing: role in diagnosis, disease monitoring and
      treatment.
AB  - While hepatitis B virus (HBV) screening relies on hepatitis B surface antigen to
      confirm HBV infection since the early days of hepatitis B disease management,
      hepatitis C virus (HCV) infection screening is based on anti-HCV testing which
      does not discriminate active from past infection. Thus to confirm infection HCV
      RNA testing has been required; recently a HCV core antigen assay became widely
      commercially available which could serve to confirm infection. That assay is less
      sensitive than current HCV RNA assays, but as more than 50% of anti-HCV positive
      persons will be HCV core antigen positive, HCV core antigen testing can be a cost
      effective and reflex test to confirm HCV infection in anti-HCV positive
      individuals and will be easier as it can be applied on the same platform. For
      treatment monitoring, more data need to be generated, but the early data
      available at present suggest that HCV core antigen may be an alternative to HCV
      RNA monitoring. With direct antivirals, HCV core antigen could even be superior
      to HCV RNA testing, as direct antivirals might already prevent virus formation
      when HCV core antigen is still produced and thereby correlates better with
      eventual viral clearance. 

PMID- 24944463
TI  - Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic
      viruses superinfection.
AB  - The hepatitis C virus (HCV) causes an acute infection that is frequently
      asymptomatic, but a spontaneous eradication of HCV infection occurs only in one
      third of patients. The remaining two-thirds develop a chronic infection that, in
      most cases, shows an indolent course and a slow progression to the more advanced
      stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC)
      develop liver cirrhosis with or without hepatocellular carcinoma. The indolent
      course of the illness may be troubled by the occurrence of a hepatic flare, i.e.,
      a spontaneous acute exacerbation of CHC due to changes in the immune response,
      immunosuppression and subsequent restoration, and is characterized by an increase
      in serum aminotransferase values, a frequent deterioration in liver fibrosis and
      necroinflammation but also a high frequency of sustained viral response to
      pegylated interferon plus ribavirin treatment. A substantial increase in serum
      aminotransferase values during the clinical course of CHC may also be a
      consequence of a superinfection by other hepatotropic viruses, namely hepatitis B
      virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus,
      particularly in geographical areas with high endemicity levels. The etiology of a
      hepatic flare in patients with CHC should always be defined to optimize follow-up
      procedures and clinical and therapeutic decisions. 

PMID- 24944464
TI  - Hepatitis C virus reactivation in cancer patients in the era of targeted
      therapies.
AB  - The purpose of this review is to summarize the evidence of hepatitis C
      reactivation in cancer patients in the era of targeted therapies. Targeted
      therapies are novel therapeutics frequently used in cancer patients. During
      treatment with targeted therapies, viral replication is one of the major problems
      that can occur. The PubMed database, ASCO, and ASCO Gastrointestinal Cancer
      Symposium abstracts were searched up until September 15, 2013 using the following
      search keywords: "targeted therapies, rituximab, alemtuzumab, brentuximab,
      hepatitis, hepatitis C reactivation, tyrosine kinase inhibitors, imatinib,
      mammalian target of rapamycin (mTOR) inhibitors, everolimus, anti-HER therapies,
      trastuzumab, pertuzumab, lapatinib, anti-epidermal growth factor receptor
      therapies, cetuximab, panitumumab, and ipilimumab". Papers considered relevant
      for the aim of this review were selected by the authors. The data about rituximab
      induced hepatic flare in hepatitis C virus (HCV) positive patients is
      controversial. However, there is the possibility of life-threatening hepatic
      flare that can develop after HCV ribonucleic acid (HCV-RNA) viral load increases.
      Routine follow-up of liver function tests should be advised. Especially in high
      risk patients, such as those with baseline chronic active hepatitis and
      cirrhosis, and where there are plans to administer rituximab concomitantly with
      corticosteroids, it is advised to have close follow-up of HCV viral load. The
      data is insufficient to make accurate statements about the association of
      alemtuzumab therapy and HCV reactivation. However, alemtuzumab may cause deep
      immunosuppression. Due to this, it is better to follow up with liver function
      tests and HCV RNA levels during alemtuzumab therapy. Brentuximab has effects on
      antibody dependent cellular toxicity and may decrease humoral immunity. Thus, we
      believe that during brentuximab treatment of HCV infected patients, clinicians
      may encounter hepatitis C reactivation. There have been no reported cases of
      hepatitis C reactivation with imatinib therapy. However, there are many reports
      of hepatitis B reactivation with imatinib treatment. Based on the evidence of
      hepatitis B reactivation with imatinib and the effects of imatinib on immune
      system functions, we suggest that imatinib therapy might be a risk factor for HCV
      reactivation. Anti-human epidermal growth factor receptor 2 therapies are not
      associated with hepatic flare in HCV infected patients. Post-transplant studies
      reported that mTOR was safely administered to patients with active hepatitis C
      without causing hepatic flare. Cetuximab and panitumumab have not been associated
      with HCV reactivation. Two cases of HCV infected melanoma were safely treated
      with ipilimumab without any HCV reactivation or hepatic flare. Targeted therapies
      are a new and emerging area of oncology treatment modalities. While treating HCV
      infected cancer patients, clinicians should be mindful of the immunosuppressive
      properties of targeted therapies. Further randomized trials are needed to
      establish algorithms for this issue. 

PMID- 24944467
TI  - Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based
      medicine.
AB  - Irritable bowel syndrome (IBS) is a chronic and debilitating functional
      gastrointestinal disorder that affects 9%-23% of the population across the world.
      The percentage of patients seeking health care related to IBS approaches 12% in
      primary care practices and is by far the largest subgroup seen in
      gastroenterology clinics. It has been well documented that these patients exhibit
      a poorer quality of life and utilize the health care system to a greater degree
      than patients without this diagnosis. The pathophysiology of IBS is not clear.
      Many theories have been put forward, but the exact cause of IBS is still
      uncertain. According to the updated ROME III criteria, IBS is a clinical
      diagnosis and presents as one of the three predominant subtypes: (1) IBS with
      constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M);
      former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS
      subtypes, the presentation of symptoms may vary among patients and change over
      time. Patients report the most distressing symptoms to be abdominal pain,
      straining, myalgias, urgency, bloating and feelings of serious illness. The
      complexity and diversity of IBS presentation makes treatment difficult. Although
      there are reviews and guidelines for treating IBS, they focus on the efficacy of
      medications for IBS symptoms using high-priority endpoints, leaving those of
      lower priority largely unreported. Therefore, the aim of this review is to
      provide a comprehensive evidence-based review of the diagnosis, pathogenesis and
      treatment to guide clinicians diagnosing and treating their patients. 

PMID- 24944466
TI  - Cognitive behavioral approach to understanding irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder, whose
      onset and precipitation are a consequence of interaction among multiple factors
      which include motility disturbances, abnormalities of gastrointestinal sensation,
      gut inflammation and infection, altered processing of afferent sensory
      information, psychological distress, and affective disturbances. Several models
      have been proposed in order to describe and explain IBS, each of them focusing on
      specific aspects or mechanisms of the disorder. This review attempts to present
      and discuss different determinants of IBS and its symptoms, from a cognitive
      behavioral therapy framework, distinguishing between the developmental
      predispositions and precipitants of the disorder, and its perpetuating cognitive,
      behavioral, affective and physiological factors. The main focus in understanding
      IBS will be placed on the numerous psychosocial factors, such as personality
      traits, early experiences, affective disturbances, altered attention and
      cognitions, avoidance behavior, stress, coping and social support. In conclusion,
      a symptom perpetuation model is proposed. 

PMID- 24944465
TI  - Gender-related differences in irritable bowel syndrome: potential mechanisms of
      sex hormones.
AB  - According to epidemiological studies, twice as many women as men are affected by
      irritable bowel syndrome (IBS) in western countries, suggesting a role for sex
      hormones in IBS pathophysiology. Despite growing evidence about the implications
      of sex hormones in IBS symptom modulation, data on mechanisms by which they
      influence disease development are sparse. This review aims to determine the state
      of knowledge about the role of sex hormones in sensorimotor dysfunctions and to
      address the possible interplay of sex hormones with common risk factors
      associated with IBS. The scientific bibliography was searched using the following
      keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol,
      progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability,
      stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian
      hormones variations along the menstrual cycle affect sensorimotor
      gastrointestinal function in both healthy and IBS populations. They can modulate
      pain processing by interacting with neuromodulator systems and the emotional
      system responsible for visceral pain perception. These hormones can also modulate
      the susceptibility to stress, which is a pivotal factor in IBS occurrence and
      symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress
      can promote immune activation or impairments of gut barrier function. In
      conclusion, whereas it is important to keep in mind that ovarian hormones cannot
      be considered as a causal factor of IBS, they arguably modulate IBS onset and
      symptomatology. However, our understanding of the underlying mechanisms remains
      limited and studies assessing the link between IBS symptoms and ovarian hormone
      levels are needed to improve our knowledge of the disease evolution with regard
      to gender. Further studies assessing the role of male hormones are also needed to
      understand fully the role of sex hormones in IBS. Finally, investigation of brain
      gut interactions is critical to decipher how stress, ovarian hormones, and female
      brain processing of pain can translate into gut dysfunctions. 

PMID- 24944468
TI  - Inflammatory colonic carcinogenesis: a review on pathogenesis and
      immunosurveillance mechanisms in ulcerative colitis.
AB  - Ulcerative colitis (UC) is characterized by repeated flare-ups of inflammation
      that can lead to oncogenic insults to the colonic epithelial. UC-associated
      carcinogenesis presents a different sequence of tumorigenic events compared to
      those that contribute to the development of sporadic colorectal cancer. In fact,
      in UC, the early events are represented by oxidative DNA damage and DNA
      methylation that can produce an inhibition of oncosuppressor genes, mutation of
      p53, aneuploidy, and microsatellite instability. Hypermethylation of tumor
      suppressor and DNA mismatch repair gene promoter regions is an epigenetic
      mechanism of gene silencing that contribute to tumorigenesis and may represent
      the first step in inflammatory carcinogenesis. Moreover, p53 is frequently
      mutated in the early stages of UC-associated cancer. Aneuploidy is an independent
      risk factor for forthcoming carcinogenesis in UC. Epithelial cell-T-cell cross
      talk mediated by CD80 is a key factor in controlling the progression from low to
      high grade dysplasia in UC-associated carcinogenesis. 

PMID- 24944470
TI  - Prognostic and predictive significance of MSI in stages II/III colon cancer.
AB  - In colon cancer, classic disease staging remains the key prognosis and treatment
      determinant. Although adjuvant chemotherapy has an established role in stage III
      colon cancer patients, in stage II it is still a subject of controversy due to
      its restriction to a small subgroup of patients with high-risk histopathologic
      features. Patients with stage II tumors form a highly heterogeneous group, with
      five-year relative overall survival rates ranging from 87.5% (IIA) to 58.4%
      (IIC). Identifying those for whom adjuvant chemotherapy would be appropriate and
      necessary has been challenging, and prognostic markers which could serve in the
      selection of patients more likely to recur or benefit from adjuvant chemotherapy
      are eagerly needed. The stronger candidate in this category seems to be
      microsatellite instability (MSI). The recently reported European Society for
      Medical Oncology guidelines suggest that MSI should be evaluated in stage II
      colorectal cancer patients in order to contribute in treatment decision-making
      regarding chemotherapy administration. The hypothetical predictive role of MSI
      regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a
      much more difficult issue to address. Almost every possible relation between MSI
      and chemotherapy outcome has been described in the adjuvant colon cancer setting
      in the international literature, and the matter is far from being settled. In
      this current report we critically evaluate the prognostic and predictive impact
      of MSI status in patients with stage II and stage III colon cancer patients. 

PMID- 24944471
TI  - Synchronous colorectal cancer: clinical, pathological and molecular implications.
AB  - Synchronous colorectal carcinoma refers to more than one primary colorectal
      carcinoma detected in a single patient at initial presentation. A literature
      review has shown that the prevalence of the disease is approximately 3.5% of all
      colorectal carcinomas. This disease has a male to female ratio of 1.8:1. The mean
      age at presentation of patients with synchronous colorectal cancer is in the
      early half of the seventh decade. Patients with inflammatory bowel diseases
      (ulcerative colitis and Crohn's disease), hereditary non-polyposis colorectal
      cancer, familial adenomatous polyposis and serrated polyps/hyperplastic polyposis
      are known to have a higher risk of synchronous colorectal carcinoma. These
      predisposing factors account for slightly more than 10% of synchronous colorectal
      carcinomas. Synchronous colorectal carcinoma is more common in the right colon
      when compared to solitary colorectal cancer. On pathological examination, some
      synchronous colorectal carcinomas are mucinous adenocarcinomas. They are usually
      associated with adenomas and metachronous colorectal carcinomas. Most of the
      patients with synchronous colorectal cancer have two carcinomas but up to six
      have been reported in one patient. Patients with synchronous colorectal carcinoma
      have a higher proportion of microsatellite instability cancer than patients with
      a solitary colorectal carcinoma. Also, limited data have revealed that in many
      synchronous colorectal carcinomas, carcinomas in the same patient have different
      patterns of microsatellite instability status, p53 mutation and K-ras mutation.
      Overall, the prognosis of patients with synchronous colorectal carcinoma is not
      significantly different from that in patients with solitary colorectal carcinoma,
      although a marginally better prognosis has been reported in patients with
      synchronous colorectal carcinoma in some series. A different management approach
      and long-term clinical follow-up are recommended for some patients with
      synchronous colorectal cancer. 

PMID- 24944472
TI  - Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the
      United States. While the American Association for the Study of Liver Diseases
      guidelines define NAFLD as hepatic steatosis detected either on histology or
      imaging without a secondary cause of abnormal hepatic fat accumulation, no
      imaging modality is recommended as standard of care for screening or diagnosis.
      Bedside ultrasound has been evaluated as a non-invasive method of diagnosing
      NAFLD with the presence of characteristic sonographic findings. Prior studies
      suggest characteristic sonographic findings for NAFLD include bright hepatic
      echoes, increased hepatorenal echogenicity, vascular blurring of portal or
      hepatic vein and subcutaneous tissue thickness. These sonographic characteristics
      have not been shown to aid bedside clinicians easily identify potential cases of
      NAFLD. While sonographic findings such as attenuation of image, diffuse
      echogenicity, uniform heterogeneous liver, thick subcutaneous depth, and enlarged
      liver filling of the entire field could be identified by clinicians from bedside
      ultrasound. The accessibility, ease of use, and low-side effect profile of
      ultrasound make bedside ultrasound an appealing imaging modality in the detection
      of hepatic steatosis. When used with appropriate clinical risk factors and
      steatosis involves greater than 33% of the liver, ultrasound can reliably
      diagnose NAFLD. Despite the ability of ultrasound in detecting moderate hepatic
      steatosis, it cannot replace liver biopsy in staging the degree of fibrosis. The
      purpose of this review is to examine the diagnostic accuracy, utility, and
      limitations of ultrasound in the diagnosis of NAFLD and its potential use by
      clinicians in routine practices. 

PMID- 24944469
TI  - Colorectal cancer: from prevention to personalized medicine.
AB  - Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the
      interaction of genetic and environmental factors. CRC develops through a gradual
      accumulation of genetic and epigenetic changes, leading to the transformation of
      normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and
      incident cancers worldwide, as well as one of the most deadly. Approximately
      1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually.
      The World Health Organization estimates an increase of 77% in the number of newly
      diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The
      incidence of CRC can benefit from different strategies depending on its stage:
      health promotion through health education campaigns (when the disease is not yet
      present), the implementation of screening programs (for detection of the disease
      in its early stages), and the development of nearly personalized treatments
      according to both patient characteristics (age, sex) and the cancer itself (gene
      expression). Although there are different strategies for screening and although
      the number of such strategies is increasing due to the potential of emerging
      technologies in molecular marker application, not all strategies meet the
      criteria required for screening tests in population programs; the three most
      accepted tests are the fecal occult blood test (FOBT), colonoscopy and
      sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is
      also the primary choice in most population-based screening programs in Europe.
      Due to its non-invasive nature and low cost, it is one of the most accepted
      techniques by population. CRC is a very heterogeneous disease, and with a few
      exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a
      small percentage of cases. The design of genetic and epigenetic marker panels
      that are able to provide maximum coverage in the diagnosis of colorectal
      neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and
      protein markers in different biological samples has been explored as strategies
      for CRC diagnosis. Although there is not yet sufficient evidence to recommend the
      analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is
      likely that given the quick progression of technology tools in molecular biology,
      increasingly sensitive and less expensive, these tools will gradually be employed
      in clinical practice and will likely be developed in mass. 

PMID- 24944474
TI  - Multispecies probiotic protects gut barrier function in experimental models.
AB  - AIM: To investigate the effect of the probiotic combination Lactibiane
      Tolerance((r)) (LT) on epithelial barrier function in vitro and in vivo. METHODS:
      The effect of the multispecies probiotic LT was assessed on several models of
      epithelial barrier function both in vitro (in basal and inflammatory conditions)
      and in vivo [visceral hypersensitivity induced by chronic stress or by colonic
      perfusion of a fecal supernatant (FSN) from patients with irritable bowel
      syndrome (IBS)]. In vitro, we measured the permeability of confluent T84 cell
      monolayers incubated with or without LT by evaluating the paracellular flux of
      macromolecules, in basal conditions and after stimulation with lipopolysaccharide
      (LPS) or with conditioned medium of colonic biopsies from IBS patients (IBS-CM).
      In vivo, male C57/Bl6 mice received orally NaCl or LT for 15 d and were submitted
      to water avoidance stress (WAS) before evaluating visceral sensitivity by
      measuring the myoelectrical activity of the abdominal muscle and the paracellular
      permeability with (51)Cr-EDTA. Permeability and sensitivity were also measured
      after colonic instillation of FSN. Tight-junctions were assessed by
      immunoblotting and TLR-4 expression was evaluated by immunohistochemistry
      RESULTS: Incubation of T84 cell monolayers with LT in basal conditions had no
      significant effect on permeability (P > 0.05 vs culture medium). By contrast,
      addition of LT bacterial bodies (LT) completely prevented the LPS-induced
      increase in paracellular permeability (P < 0.01 vs LPS 10 ng/mL (LPS 10); P <
      0.01 vs LPS 100 ng/mL (LPS 100), P > 0.05 vs culture medium). The effect was dose
      dependent as addition of 10(9) LT bacterial bodies induced a stronger decrease in
      absorbance than 10(6) LT (10(9) LT + LPS 10: -20.1% +/- 13.4, P < 0.01 vs LPS 10;
      10(6) LT + LPS 10: -11.6% +/- 6.2, P < 0.01 vs LPS 10; 10(9) LT + LPS 100: -14.4%
      +/- 5.5, P < 0.01 vs LPS 100; 10(6) LT + LPS 100: -11.6% +/- 7.3, P < 0.05 vs LPS
      100). Moreover, the increase in paracellular permeability induced by culturing
      T84 cells with conditioned medium of colonic biopsies from IBS patients (IBS-CM)
      was completely inhibited in the presence of 10(9) LT (P < 0.01 vs IBS-CM). LT
      also significantly prevented the epithelial disruption induced by intracolonic
      infusion of fecal supernatant from IBS patients (P < 0.01 vs IBS FSN) or water
      avoidance stress P < 0.01 vs WAS) in C57/Bl6 mice and increased the expression of
      occludin in vitro and in vivo, as assessed by immnunoblotting. The WAS-induced
      effect on visceral sensitivity was prevented by LT treatment since values
      obtained for all steps of colorectal distension were significantly (P < 0.01)
      different from the WAS group. Finally, LT down-regulated the response mediated
      through TLR-4 in vitro (decrease in tumor necrosis factor alpha secretion in
      response to LPS: -65.8% for 10(9) LT and -52.5% for 10(6) LT, P < 0.01 vs LPS)
      and in vivo (inhibition of WAS induced an increase in TLR-4 expression in the LT
      treated mice colon, P < 0.01 vs WAS). CONCLUSION: The probiotic LT mix prevented
      the disruption to the epithelial barrier induced by LPS, stress or colonic
      soluble factors from IBS patients and prevented visceral hypersensitivity.

PMID- 24944473
TI  - Input of microenvironmental regulation on colorectal cancer: role of the CCN
      family.
AB  - Colorectal cancer (CRC) is a major health problem causing significant morbidity
      and mortality. Previous results from various studies indicate that CRC
      tumorigenicity encompasses tumor microenvironment, emphasizing the complex
      interacting network between cancer cells and nearby host cells, which triggers
      diverse signaling pathways to promote the growth and spread of cancer cells. The
      CCN family proteins share a uniform modular structure, mediating a variety of
      physiological functions, including proliferation, apoptosis, migration, adhesion,
      differentiation, and survival. Furthermore, CCN proteins are also involved in CRC
      initiation and development. Many studies have shown that CCN members, such as
      CCN1, CCN2, CCN3, Wnt-induced secreted protein (WISP)-1, WISP-2, and WISP-3, are
      dysregulated in CRC, which implies potential diagnostic markers or therapeutic
      targets clinically. In this review, we summarize the research findings on the
      role of CCN family proteins in CRC initiation, development, and progression,
      highlighting their potential for diagnosis, prognosis, and therapeutic
      application.

PMID- 24944475
TI  - Role of the Na +/K +/2Cl- cotransporter NKCC1 in cell cycle progression in human
      esophageal squamous cell carcinoma.
AB  - AIM: To investigate the role of Na(+)/K(+)/2Cl(-) cotransporter 1 (NKCC1) in the
      regulation of genes involved in cell cycle progression and the
      clinicopathological significance of its expression in esophageal squamous cell
      carcinoma (ESCC). METHODS: An immunohistochemical analysis was performed on 68
      primary tumor samples obtained from ESCC patients that underwent esophagectomy.
      NKCC1 expression in human ESCC cell lines was analyzed by Western blotting.
      Knockdown experiments were conducted using NKCC1 small interfering RNA, and the
      effects on cell cycle progression were analyzed. The gene expression profiles of
      cells were analyzed by microarray analysis. RESULTS: Immunohistochemical staining
      showed that NKCC1 was primarily found in the cytoplasm of carcinoma cells and
      that its expression was related to the histological degree of differentiation of
      SCC. NKCC1 was highly expressed in KYSE170 cells. Depletion of NKCC1 in these
      cells inhibited cell proliferation via G2/M phase arrest. Microarray analysis
      identified 2527 genes with altered expression levels in NKCC1depleted KYSE170.
      Pathway analysis showed that the top-ranked canonical pathway was the G2/M DNA
      damage checkpoint regulation pathway, which involves MAD2L1, DTL, BLM, CDC20,
      BRCA1, and E2F5. CONCLUSION: These results suggest that the expression of NKCC1
      in ESCC may affect the G2/M checkpoint and may be related to the degree of
      histological differentiation of SCCs. We have provided a deeper understanding of
      the role of NKCC1 as a mediator and/or a biomarker in ESCC.

PMID- 24944477
TI  - Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial
      livers.
AB  - AIM: To construct and evaluate the functionality of a choanoid-fluidized bed
      bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.
      METHODS: Encapsulated hepatocytes were placed in the constructed CFBB and
      circulated through Dulbecco's Modified Eagle's Medium (DMEM) for 12 h, and then
      through exchanged plasma for 6 h, and compared with encapsulated cells cultivated
      under static conditions in a spinner flask. Levels of alanine aminotransferase
      (ALT) and albumin were used to evaluate the CFBB during media circulation,
      whereas levels of ALT, total bilirubin (TBil), and albumin were used to evaluate
      it during plasma circulation. Mass transfer and hepatocyte injury were evaluated
      by comparing the results from the two experimental conditions. In addition, the
      viability and microstructure of encapsulated cells were observed in the different
      environments. RESULTS: The bioartificial liver model based on a CFBB was verified
      by in vitro experiments. The viability of encapsulated cells accounting for 84.6%
      +/- 3.7% in CFBB plasma perfusion was higher than the 74.8% +/- 3.1% in the
      static culture group (P < 0.05) after 6 h. ALT release from cells was 29 +/- 3.5
      U/L vs 40.6 +/- 3.2 U/L at 12 h (P < 0.01) in the CFBB medium circulation and
      static medium culture groups, respectively. Albumin secretion from cells was
      234.2 +/- 27.8 MUg/1 * 10(7) cells vs 167.8 +/- 29.3 MUg/1 * 10(7) cells at 6 h
      (P < 0.01), 274.4 +/- 34.6 MUg/1 * 10(7) cells vs 208.4 +/- 49.3 MUg/1 * 10(7)
      cells (P < 0.05) at 12 h, in the two medium circulation/culture groups,
      respectively. Furthermore, ALT and TBil levels were 172.3 +/- 24.1 U/L vs 236.3
      +/- 21.5 U/L (P < 0.05), 240.1 +/- 23.9 MUmol/L vs 241.9 +/- 31.4 MUmol/L (P >
      0.05) at 6 h in the CFBB plasma perfusion and static plasma culture groups,
      respectively. There was no significant difference in albumin concentration
      between the two experimental plasma groups at any time point. The microstructure
      of the encapsulated hepatocytes remained healthier in the CFBB group compared
      with the static culture group after 6 h of plasma perfusion. CONCLUSION: The CFBB
      can function as a bioartificial liver based on a bioreactor. The efficacy of this
      novel bioreactor is promising for the study of liver failure.

PMID- 24944478
TI  - Laparoendoscopic single-site distal pancreatectomy in pigs.
AB  - AIM: To explore the technique for laparoendoscopic single-site distal
      pancreatectomy. METHODS: Laparoendoscopic single-site spleen-preserving distal
      pancreatectomy was performed in pigs using a novel flexible multichannel port, a
      curved laparoscopic multifunctional operative device and a fish hook retractor,
      which provided a favorable operative field. RESULTS: Six pigs were involved in
      this study, and five survived the procedure. The first animal died following
      injury to the superior mesenteric vein and uncontrolled intraoperative bleeding.
      Except for this failure, the mean operative time was 155 min (range: 102-236
      min). A steep learning curve was observed in the study, with a mean operative
      time of 177 min in the first two operations vs 134 min in the last three
      operations. The mean blood loss was 50 mL, and the postoperative course was
      uneventful. The animals were sacrificed three weeks after the procedures, and no
      pancreatic leakage or abdominal infection was found macroscopically. CONCLUSION:
      Laparoendoscopic single-site distal pancreatectomy is a safe and feasible
      procedure and can be implemented in humans in selected cases at qualified
      surgical centers.

PMID- 24944476
TI  - Carcinogenic Helicobacter pylori in gastric pre-cancer and cancer lesions:
      association with tobacco-chewing.
AB  - AIM: To investigate the low gastric cancer incidence rate relative to the highly
      prevalent Helicobacter pylori (H. pylori) infection; data relevant to H. pylori
      infection during gastric carcinogenesis in Indian patients is currently lacking.
      METHODS: The present study examines the prevalence of H. pylori infection in DNA
      derived from 156 endoscopic gastric biopsies of different disease groups that
      represent gastric pre-cancer [intestinal metaplasia (n = 15), dysplasia (n =
      15)], cancer [diffuse adenocarcinoma (n = 44), intestinal adenocarcinoma (n =
      21)], and symptomatic but histopathologically-normal controls (n = 61). This was
      done by generic ureC polymerase chain reaction (PCR) and cagA-specific PCR that
      could specifically identify the carcinogenic H. pylori strain. RESULTS: Our
      analysis showed the presence of H. pylori infection in 61% of symptomatic
      histopathologically-normal individuals, however only 34% of control tissues were
      harboring the cagA(+) H. pylori strain. A similar proportion of H. pylori
      infection (52%) and cagA (26%) positivity was observed in the tumor tissue of the
      gastric cancer group. In comparison, H. pylori infection (90%) and cagA
      positivity (73%) were the highest in gastric pre-cancer lesions. In relation to
      tobacco and alcohol abuse, H. pylori infection showed an association with tobacco
      chewing, whereas we did not observe any association between tobacco smoking or
      alcohol abuse with prevalence of H. pylori infection in the tissue of any of the
      patient groups studied. CONCLUSION: High incidence of H. pylori infection and
      carcinogenic cagA positive strain in pre-cancer lesions during gastric
      carcinogenesis may be associated with the habit of chewing tobacco.

PMID- 24944479
TI  - Mesothelin promotes cell proliferation in the remodeling of neonatal rat
      pancreas.
AB  - AIM: To investigate the effect of mesothelin in the remodeling of the endocrine
      pancreas in neonatal rats. METHODS: Overexpression or downregulation of
      mesothelin expression in INS-1 cells was carried out to investigate the effect of
      mesothelin during cell proliferation and cell apoptosis in vitro. Adenovirus
      mediated RNA interference was performed to block mesothelin in vivo to directly
      assess the role of mesothelin in the remodeling of the endocrine pancreas in
      neonatal rats. RESULTS: Exogenous overexpression of mesothelin promoted cell
      proliferation, cell colony formation and enhanced cell resistance to apoptosis of
      INS-1 cells. Down-regulation of mesothelin made no difference in cell
      proliferation and apoptosis compared with that in the control group. After an
      injection of adenovirus-mesothelin, a significantly increased number of small
      islets appeared, and the expression of PCNA was decreased on day 7 and day 14
      compared with the Ad-EGFP group. CONCLUSION: Mesothelin was able to promote beta
      cell proliferation in the remodeling stage of neonatal rats. Mesothelin may have
      an important role in the remodeling of the endocrine pancreas in neonatal rats.

PMID- 24944481
TI  - Reduced expression of circulating microRNA-218 in gastric cancer and correlation
      with tumor invasion and prognosis.
AB  - AIM: To investigate the expression of microRNA-218 (miR-218) in serum from
      gastric cancer patients and its relationship with clinicopathological
      characteristics. METHODS: A total of 68 patients with pathologically diagnosed
      gastric cancer and 56 healthy individuals were recruited to this study. The
      expression of miR-218 was detected in the serum of gastric cancer patients and
      healthy individuals by quantitative real-time polymerase chain reaction. The
      clinical data were collected and analyzed by statistical software. RESULTS: miR
      218 was reduced significantly in the serum of gastric cancer patients compared to
      healthy individuals (1.15 +/- 0.08 vs 0.37 +/- 0.023; P = 0.026). In the gastric
      cancer group, serum expression of miR-218 was lower in patients with metastasis
      and poorly differentiated cancer compared with non-metastatic and well
      differentiated cancer (0.19 +/- 0.011 vs 0.45 +/- 0.021, P = 0.031 and 0.21 +/-
      0.019 vs 0.49 +/- 0.021, P = 0.025). Serum miR-218 was found to be significantly
      associated with gastric cancer metastasis (P = 0.003), tumor T stage (P = 0.018)
      and tumor grade (P = 0.012). Low serum expression of miR-218 was related to an
      increase in the stage of gastric cancer. The expression level of miR-218 in the
      serum was correlated with the 3-year survival. Ninety-seven percent of patients
      with a high level of miR-218 expression survived for 3 years, while only 54% of
      those with low miR-218 expression survived. CONCLUSION: miR-218 is deregulated in
      gastric cancer patients and is strongly correlated with tumor stage, grade and
      metastasis. Serum expression of miR-218 may be a prognostic marker.

PMID- 24944480
TI  - Expression of gastrointestinal nesfatin-1 and gastric emptying in ventromedial
      hypothalamic nucleus- and ventrolateral hypothalamic nucleus-lesioned rats.
AB  - AIM: To determine the expression levels of gastrointestinal nesfatin-1 in
      ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral
      hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imbalance in
      their energy metabolism and gastric mobility. METHODS: Male Wistar rats were
      randomly divided into a VMH-lesioned group, a VLH-lesioned group, and their
      respective sham-operated groups. The animals had free access to food and water,
      and their diets and weights were monitored after surgery. Reverse transcription
      polymerase chain reaction and immunostaining were used to analyse the levels of
      NUCB2 mRNA and nesfatin-1 immunoreactive (IR) cells in the stomach, duodenum,
      small intestine, and colon, respectively. Gastric emptying was also assessed
      using a modified phenol red-methylcellulose recovery method. RESULTS: The VMH
      lesioned rats fed normal chow exhibited markedly greater food intake and body
      weight gain, whereas the VLH-lesioned rats exhibited markedly lower food intake
      and body weight gain. NUCB2/nesfatin-1 IR cells were localised in the lower third
      and middle portion of the gastric mucosal gland and in the submucous layer of the
      enteric tract. Compared with their respective controls, gastric emptying was
      enhanced in the VMH-lesioned rats (85.94% +/- 2.27%), whereas the VLH lesions
      exhibited inhibitory effects on gastric emptying (29.12% +/- 1.62%). In the VMH
      lesioned rats, the levels of NUCB2 mRNA and nesfatin-1 protein were significantly
      increased in the stomach and duodenum and reduced in the small intestine. In
      addition, the levels of NUCB2 mRNA and nesfatin-1 protein in the VLH-lesioned
      rats were decreased in the stomach, duodenum, and small intestine. CONCLUSION:
      Our study demonstrated that nesfatin-1 level in the stomach and duodenum is
      positively correlated with body mass. Additionally, there is a positive
      relationship between gastric emptying and body mass. The results of this study
      indicate that gastrointestinal nesfatin-1 may play a significant role in gastric
      mobility and energy homeostasis.

PMID- 24944483
TI  - Helicobacter pylori eradication in patients with chronic immune thrombocytopenic
      purpura.
AB  - AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on
      platelet counts in patients with chronic immune thrombocytopenic purpura (cITP).
      METHODS: A total of 36 cITP patients were included in the study. The diagnosis of
      H. pylori was done by rapid urease test and Giemsa staining of the gastric biopsy
      specimen. All H. pylori positive patients received standard triple therapy for 14
      d and were subjected for repeat endoscopy at 6 wk. Patients who continued to be
      positive for H. pylori on second endoscopy received second line salvage therapy.
      All the patients were assessed for platelet response at 6 wk, 3(rd) and 6(th)
      months. RESULTS: Of the 36 patients, 17 were positive for H. pylori infection and
      eradication was achieved in 16 patients. The mean baseline platelet count in the
      eradicated patients was 88615.38 +/- 30117.93/mm(3) and platelet count after
      eradication at 6 wk, 3 mo and 6 mo was 143230.77 +/- 52437.51/mm(3) (P = 0.003),
      152562.50 +/- 52892.3/mm(3) (P = 0.0001), 150187.50 +/- 41796.68/mm(3) (P =
      0.0001) respectively and in the negative patients, the mean baseline count was
      71000.00 +/- 33216.46/mm(3) and at 6 wk, 3(rd) and 6(th) month follow up was
      137631.58 +/- 74364.13/mm(3) (P = 0.001), 125578.95 +/- 71472.1/mm(3) (P =
      0.005), 77210.53 +/- 56892.28/mm(3) (P = 0.684) respectively. CONCLUSION:
      Eradication of H. pylori leads to increase in platelet counts in patients with
      cITP and can be recommended as a complementary treatment with conventional
      therapy.

PMID- 24944482
TI  - Serum adipokines in inflammatory bowel disease.
AB  - AIM: To investigate serum adipokine levels in inflammatory bowel disease (IBD)
      patients before treatment and after achieving clinical remission. METHODS: Serum
      concentrations of six adipokines (tissue growth factor-beta1, adiponectin,
      leptin, chemerin, resistin, and visfatin) were studied in 40 subjects with active
      IBD [24 subjects with Crohn's disease (CD) and in 16 subjects with ulcerative
      colitis (UC)] before and after three months of therapy with corticosteroids
      and/or azathioprine. Clinical diagnoses were based on ileocolonoscopy, computed
      tomography or magnetic resonance enterography and histological examination of
      mucosal biopsies sampled during endoscopy. Serum levels of adipokines were
      assessed by an indirect enzyme-linked immunosorbent assay. The control group was
      comprised of 16 age- and sex-matched healthy volunteers. RESULTS: Baseline leptin
      concentrations were significantly decreased in both types of IBD compared to
      controls (8.0 +/- 9.1 in CD and 8.6 +/- 6.3 in UC vs 16.5 +/- 10.1 ng/mL in
      controls; P < 0.05), and significantly increased after treatment only in subjects
      with CD (14.9 +/- 15.1 ng/mL; P < 0.05). Baseline serum resistin concentrations
      were significantly higher in CD (19.3 +/- 12.5 ng/mL; P < 0.05) and UC subjects
      (23.2 +/- 11.0 ng/mL; P < 0.05) than in healthy controls (10.7 +/- 1.1 ng/mL).
      Treatment induced a decrease in the serum resistin concentration only in UC
      subjects (14.5 +/- 4.0 ng/mL; P < 0.05). Baseline serum concentrations of
      visfatin were significantly higher in subjects with CD (23.2 +/- 3.2 ng/mL; P <
      0.05) and UC (18.8 +/- 5.3 ng/mL; P < 0.05) than in healthy controls (14.1 +/-
      5.3 ng/mL). Treatment induced a decrease in the serum visfatin concentrations
      only in CD subjects (20.4 +/- 4.8 ng/mL; P < 0.05). Serum levels of adiponectin,
      chemerin and tissue growth factor-beta1 did not differ between CD and UC subjects
      compared to healthy controls and also were not altered by anti-inflammatory
      therapy. Clinical indices of IBD activity did not correlate with adipokine
      levels. CONCLUSION: IBD modulates serum adipokine levels by increasing resistin
      and visfatin release and suppressing leptin production.

PMID- 24944485
TI  - Helicobacter pylori eradication with moxifloxacin-containing therapy following
      failed first-line therapies in South Korea.
AB  - AIM: To investigate moxifloxacin-containing triple therapy as second-line
      treatment for Helicobacter pylori (H. pylori) infection following failed first
      line treatment. METHODS: The sample included 312 patients for whom first-line
      treatment failed between January 2008 and May 2013; 27 patients were excluded,
      and a total of 285 patients received 7- or 14-d moxifloxacin-containing triple
      therapy as second-line treatment for H. pylori infection. First line regimens
      included 7-d standard triple (n = 172), 10-d bismuth-containing quadruple (n =
      28), 14-d concomitant (n = 37), or 14-d sequential (n = 48) therapy. H. pylori
      status was evaluated using (13)C-urea breath testing 4 wk later, after completion
      of the treatment. The primary outcome was the H. pylori eradication rate analyzed
      using intention-to-treat (ITT) and per protocol (PP) analyses. The secondary
      outcome was the occurrence of serious adverse events. Demographic and clinical
      factors were analyzed using Student's t-tests and Pearson's chi(2) tests
      according to first- and second-line regimens. A P value of less than 0.05 was
      considered statistically significant. RESULTS: The eradication rate of
      moxifloxacin-containing triple therapy was 68.4% (ITT; 95%CI: 62.8-73.5) and
      73.9% (PP; 95%CI: 68.3-78.8). The eradication rate was significantly higher with
      14 d compared to 7 d of treatment (77.5% vs 62.5%, P = 0.017). Peptic ulcer
      patients had a higher eradication rate than the patients without ulcers (82.9% vs
      70.6%, P = 0.046). The demographic and clinical characteristics were not
      significantly different between the groups according to first-line therapies. ITT
      and PP analyses of the moxifloxacin-containing triple therapy indicated the
      following eradication rates: 70.9% (95%CI: 63.8-77.2) and 77.2% (95%CI: 70.1
      83.1) for standard triple; 67.9% (95%CI: 51.5-84.2) and 67.9% (95%CI: 51.5-84.2)
      for bismuth-containing quadruple; 60.4% (95%CI: 46.3-73.0) and 70.7% (95%CI: 54.0
      80.9) for sequential; and 67.6% (95%CI: 51.5-80.4) and 67.6%(95%CI: 51.5-80.4)
      for concomitant therapy. There were no statistically significant differences in
      the efficacy of the first-line regimens (P = 0.492). The most common adverse
      event was diarrhea. There were no serious adverse events and no significant
      differences in the frequency of side effects between the first- and second-line
      regimens (28.7% vs 26.1%, respectively). CONCLUSION: Moxifloxacin-containing
      triple therapy as second-line treatment resulted in low eradication rates. There
      were no differences in the efficacy between the first-line regimens in South
      Korea.

PMID- 24944484
TI  - Non-surgical treatment of post-surgical bile duct injury: clinical implications
      and outcomes.
AB  - AIM: To investigate the prognostic factors determining the success rate of non
      surgical treatment in the management of post-operative bile duct injuries (BDIs).
      METHODS: The study patients were enrolled from the pancreatobiliary units of a
      tertiary teaching hospital for the treatment of BDIs after hepatobiliary tract
      surgeries, excluding operations for liver transplantation and malignancies, from
      January 1999 to August 2010. A total of 5167 patients underwent operations, and
      77 patients had BDIs following surgery. The primary end point was the treatment
      success rate according to different types of BDIs sustained using endoscopic or
      percutaneous hepatic approaches. The type of BDI was defined using one of the
      following diagnostic tools: endoscopic retrograde cholangiography, percutaneous
      transhepatic cholangiography, computed tomography scan, and magnetic resonance
      cholangiography. Patients with a final diagnosis of BDI underwent endoscopic
      and/or percutaneous interventions for the treatment of bile leak and/or stricture
      if clinically indicated. Patient consent was obtained, and study approval was
      granted by the Institutional Review Board in accordance with the legal
      regulations of the Human Clinical Research Center at the Seoul National
      University Hospital in Seoul, South Korea. RESULTS: A total of 77 patients were
      enrolled in the study. They were divided into three groups according to type of
      BDI. Among them, 55 patients (71%) underwent cholecystectomy. Thirty-six patients
      (47%) had bile leak only (type 1), 31 patients had biliary stricture only (type
      2), and 10 patients had both bile leak and biliary stricture (type 3). Their
      initial treatment modalities were non-surgical. The success rate of non-surgical
      treatment in each group was as follows: BDI type 1: 94%; type 2: 71%; and type 3:
      30%. Clinical parameters such as demographic factors, primary disease, operation
      method, type of operation, non-surgical treatment modalities, endoscopic
      procedure steps, type of BDI, time to diagnosis and treatment duration were
      evaluated to evaluate the prognostic factors affecting the success rate. The type
      of BDI was a statistically significant prognostic factor in determining the
      success rate of non-surgical treatment. In addition, a shorter time to diagnosis
      of BDI after the operation correlated significantly with higher success rates in
      the treatment of type 1 BDIs. CONCLUSION: Endoscopic or percutaneous hepatic
      approaches can be used as an initial treatment in type 1 and 2 BDIs. However,
      surgical intervention is a treatment of choice in type 3 BDI.

PMID- 24944486
TI  - Solid pseudopapillary tumor of the pancreas in male patients: report of 16 cases.
AB  - AIM: To investigate the clinical characteristics, surgical strategies and
      prognosis of solid pseudopapillary tumors (SPTs) of the pancreas in male
      patients. METHODS: From July 2003 to March 2013, 116 patients were diagnosed with
      SPT of the pancreas in our institution. Of these patients, 16 were male. The
      patients were divided into two groups based on gender: female (group 1) and male
      (group 2). The groups were compared with regard to demographic characteristics,
      clinical presentations, surgical strategies, complications and follow-up
      outcomes. RESULTS: Male patients were older than female patients (43.1 +/- 12.3
      years vs 33.1 +/- 11.5 years, P = 0.04). Tumor size, location, and symptoms were
      comparable between the two groups. All patients, with the exception of one,
      underwent complete surgical resection. The patients were regularly followed up.
      The mean follow-up period was 58 mo. Two female patients (1.7%) developed tumor
      recurrence or metastases and required a second resection, and two female patients
      (1.7%) died during the follow-up period. CONCLUSION: Male patients with SPT of
      the pancreas are older than female patients. There are no significant differences
      between male and female patients regarding surgical strategies and prognosis.

PMID- 24944487
TI  - Diabetes mellitus increases risk for colorectal adenomas in younger patients.
AB  - AIM: To determine if diabetes mellitus (DM) is associated with increased risk of
      colorectal adenomas in younger subjects. METHODS: This was a retrospective cohort
      study of 375 patients undergoing index colonoscopy at a single tertiary care
      center in the United States. Three cohorts of patients matched for exam date and
      gender were compared: (1) ages 40-49 years with DM; (2) ages 40-49 years without
      DM; and (3) ages 50-59 years without DM. Data collected included demographics, co
      morbidities, colonoscopy and pathology results. Adenoma detection rates (ADR)
      were calculated and compared. Conditional logistic regression analysis was
      performed to determine the association between each cohort and ADR. RESULTS: One
      hundred and twenty-five patients ages 40-49 with DM met study eligibility
      criteria. Patients in the other two cohorts were randomly selected, matching for
      date of exam and gender. ADR was 14.4% in those ages 40-49 years without DM,
      30.4% in those ages 40-49 years with DM, and 32.0% in those ages 50-59 years
      without DM. Compared to those ages 40-49 years without DM, ADR was higher in
      those ages 40-49 years with DM (OR = 3.1; 95%CI: 1.5-6.4; P = 0.002) and those
      ages 50-59 years without DM (OR = 2.9; 95%CI: 1.5-5.6; P = 0.002). There was no
      difference between the ADR in those ages 40-49 years with DM and those ages 50-59
      years without DM (P = 0.83). CONCLUSION: DM was associated with higher risk of
      colorectal adenomas in patients ages 40-49 years. These subjects harbored as many
      adenomas as those at the standard screening age of 50-59 years without DM.

PMID- 24944488
TI  - Liver regeneration after liver resection: clinical aspects and correlation with
      infective complications.
AB  - AIM: To investigate whether early liver regeneration after resection in patients
      with hepatic tumors might be influenced by post-operative infective
      complications. METHODS: A retrospective analysis of 27 liver resections for
      tumors performed in a single referral center from November 2004 to January 2010.
      Regeneration was evaluated by multidetector computed tomography at a mean follow
      up of 43.85 d. The Clavien-Dindo classification was used to evaluate
      postoperative events in the first 6 mo after transplantation, and Centers for
      Disease Control and Prevention definitions were used for healthcare associated
      infections data. Generalized linear regression models with Gaussian family
      distribution and log link function were used to reveal the principal promoters of
      early liver regeneration. RESULTS: Ten of the 27 patients (37%) underwent
      chemotherapy prior to surgery, with a statistically significant prevalence of
      patients with metastasis (P = 0.007). Eight patients (30%) underwent
      embolization, 3 with primary tumors, and 5 with secondary tumors. Twenty patients
      (74%) experienced complications, with 12 (60%) experiencing Clavien-Dindo Grade
      3a to 5 complications. Regeneration >= 100% occurred in 10 (37%) patients. The
      predictors were smaller future remnant liver volume (-0.002; P < 0.001), and a
      greater spleen volume/future remnant liver volume ratio (0.499; P = 0.01).
      Patients with a resection of >= 5 Couinaud segments experienced greater early
      regeneration (P = 0.04). Nine patients experienced surgical site infections, and
      in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected (P = 0.016).
      There were no significant differences between patients with primary or secondary
      tumors, and either onset or infections or severity of surgical complications.
      CONCLUSION: Regardless of the onset of infective complications, future remnant
      liver and spleen volumes may be reliable predictors of early liver regeneration
      after hepatic resection on an otherwise healthy liver.

PMID- 24944489
TI  - Factors associated with incomplete colonoscopy at a Japanese academic hospital.
AB  - AIM: To evaluate significant risk factors for incomplete colonoscopy at a
      Japanese academic hospital. METHODS: A total of 11812 consecutive Japanese people
      were identified who underwent a colonoscopy at an academic hospital. A multiple
      logistic regression model was used to evaluate retrospectively the significant
      risk factors for incomplete colonoscopy. RESULTS: The cecal intubation rate was
      95.0%. By univariate analysis, age, female sex, poor bowel cleansing, and a
      history of abdominal or pelvic surgery were significant risk factors for
      incomplete colonoscopy (P < 0.001). Moreover, age- and sex-adjusted analysis
      showed that significant risk factors for incomplete colonoscopy were female sex
      (OR = 1.38, 95%CI: 1.17-1.64, P = 0.0002), age >= 60 years old (OR = 1.44, 95%CI:
      1.22-1.71, P < 0.0001), a history of prior abdominal or pelvic surgery (OR =
      1.55, 95%CI: 1.28-1.86, P < 0.0001), poor bowel cleansing (OR = 4.64, 95%CI: 3.69
      5.84, P < 0.0001), and inflammatory bowel disease (IBD) (OR = 1.48, 95%CI: 1.13
      1.95, P = 0.0048). In Japanese men, by age-adjusted analysis, IBD (OR = 1.69,
      95%CI: 1.18-2.43, P = 0.005) was an independent risk factor for incomplete
      colonoscopy. CONCLUSION: Several characteristics in the Japanese population were
      identified that could predict technical difficulty with colonoscopy.

PMID- 24944490
TI  - Evaluation of endoscopic biliary stenting for obstructive jaundice caused by
      hepatocellular carcinoma.
AB  - AIM: To review the usefulness of endoscopic biliary stenting for obstructive
      jaundice caused by hepatocellular carcinoma and identify problems that may need
      to be addressed. METHODS: The study population consisted of 36 patients with
      obstructive jaundice caused by hepatocellular carcinoma (HCC) who underwent
      endoscopic biliary stenting (EBS) as the initial drainage procedure at our
      hospital. The EBS technical success rate and drainage success rate were assessed.
      Drainage was considered effective when the serum total bilirubin level decreased
      by 50% or more following the procedure compared to the pre-drainage value.
      Survival time after the procedure and patient background characteristics were
      assessed comparatively between the successful drainage group (group A) and the
      non-successful drainage group (group B). The EBS stent patency duration in the
      successful drainage group (group A) was also assessed. RESULTS: The technical
      success rate was 100% for both the initial endoscopic nasobiliary drainage and
      EBS in all patients. Single stenting was placed in 21 patients and multiple
      stenting in the remaining 15 patients. The drainage successful rate was 75% and
      the median interval to successful drainage was 40 d (2-295 d). The median
      survival time was 150 d in group A and 22 d in group B, with the difference
      between the two groups being statistically significant (P < 0.0001). There were
      no statistically significant differences between the two groups with respect to
      patient background characteristics, background liver condition, or tumor factors;
      on the other hand, the two groups showed statistically significant differences in
      patients without a history of hepatectomy (P = 0.009) and those that received
      multiple stenting (P = 0.036). The median duration of stent patency was 43 d in
      group A (2-757 d). No early complications related to the EBS technique were
      encountered. Late complications occurred in 13 patients (36.1%), including stent
      occlusion in 7, infection in 3, and distal migration in 3. CONCLUSION: EBS is
      recommended as the initial drainage procedure for obstructive jaundice caused by
      HCC, as it appears to contribute to prolongation of survival time.

PMID- 24944491
TI  - Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b
      expression in liver cancer stem cells.
AB  - AIM: To determine the influence of Adriamycin (ADM) on the changes in Nanog,
      Oct4, Sox2, as well as, in ARID1 and Wnt5b expression in liver cancer stem cells.
      METHODS: The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the
      cell models in this study, and were routinely cultured. The 50% lethal dose
      (LD50) in the cell lines was detected by the MTT assay. Expression changes in
      liver cancer stem cell related genes (Nanog, Oct-4, Sox2, ARID1, and Wnt5b) were
      detected by western blot following treatment with ADM (LD50). RESULTS: The LD50
      of ADM in MHCC97-L cells was lower than that in HCCLM3 cells (0.4123 +/- 0.0236
      MUmol/L vs 0.5259 +/- 0.0125 MUmol/L, P < 0.05). Wnt5b and Nanog were expressed
      in both MHCC97-L and HCCLM3 cells, while only Sox2 was expressed in HCCLM3 cells.
      However, neither ARID1A nor Oct4 was detected in these two cell lines. Genes,
      related to the stem cells, showed different expression in liver cancer cells with
      different metastatic potential following treatment with ADM (LD50). Wnt5b protein
      increased gradually within 4 h of ADM (LD50) treatment, while Nanog decreased (P
      < 0.05). After 12 h, Wnt5b decreased gradually, while Nanog increased steadily (P
      < 0.05). In addition, only Sox2 was expressed in HCCLM3 cells with high
      metastatic potential following ADM (LD50) treatment. The expression of Sox2
      increased gradually with ADM (LD50) in HCCLM3 cells (P < 0.05). CONCLUSION: ADM
      increased the death rate of MHCC97-L and HCCLM3 cells, while the growth
      suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.

PMID- 24944492
TI  - Should peri-gastrectomy gastric acidity be our focus among gastric cancer
      patients?
AB  - AIM: To investigate the necessity and correctness of acid suppression pre- and
      post-gastrectomy among gastric carcinoma (GC) patients. METHODS: From June 2011
      to April 2013, 99 patients who were diagnosed with GC or adenocarcinoma of the
      gastroesophageal junction (type II or III) and needed surgical management were
      enrolled. They all underwent gastrectomy by the same operators [35 undergoing
      total gastrectomy (TG) plus Roux-en-Y reconstruction, 34 distal gastrectomy (DG)
      plus Billroth I reconstruction, and 30 proximal gastrectomy (PG) plus
      gastroesophagostomy]. We collected and analyzed their gastrointestinal juice and
      tissues from the pre-operational day to the 5(th) day post-operation, and 6 mo
      post-surgery. Gastric pH was detected with a precise acidity meter. Gastric juice
      contents including potassium, sodium and bicarbonate ions, urea nitrogen, direct
      and indirect bilirubin, and bile acid were detected using Automatic Biochemical
      Analyzer. Data regarding tumor size, histological type, tumor penetration and
      tumor-node-metastasis (TNM) stage were obtained from the pathological records.
      Reflux symptoms pre- and 6 mo post-gastrectomy were evaluated by reflux disease
      questionnaire (RDQ) and gastroesophageal reflux disease questionnaire (GERD-Q).
      SPSS 16.0 was applied to analyze the data. RESULTS: Before surgery, gastric pH
      was higher than the threshold of hypoacidity (4.25 +/- 1.45 vs 3.5, P = 0.000),
      and significantly affected by age, tumor size and differentiation grade, and
      potassium and bicarbonate ions; advanced malignancies were accompanied with
      higher pH compared with early ones (4.49 +/- 1.31 vs 3.66 +/- 1.61, P = 0.008).
      After operation, gastric pH in all groups was of weak-acidity and significantly
      higher than that pre-gastrectomy; on days 3-5, comparisons of gastric pH were
      similar between the 3 groups. Six months later, gastric pH was comparable to that
      on days 3-5; older patients were accompanied with higher total bilirubin level,
      indicating more serious reflux (r = 0.238, P = 0.018); the TG and PG groups had
      higher RDQ (TG vs DG: 15.80 +/- 5.06 vs 12.26 +/- 2.14, P = 0.000; PG vs DG:
      15.37 +/- 3.49 vs 12.26 +/- 2.14, P = 0.000) and GERD-Q scores (TG vs DG: 10.54
      +/- 3.16 vs 9.15 +/- 2.27, P = 0.039; PG vs DG: 11.00 +/- 2.07 vs 9.15 +/- 2.27,
      P = 0.001) compared with the DG group; all gastric juice contents except
      potassium ion significantly rose; reflux symptom was significantly associated
      with patient's body mass index, direct and indirect bilirubin, and total bile
      acid, while pH played no role. CONCLUSION: Acidity is not an important factor
      causing unfitness among GC patients. There is no need to further alkalify
      gastrointestinal juice both pre- and post-gastrectomy.

PMID- 24944493
TI  - New index to predict esophageal variceal bleeding in cirrhotic patients.
AB  - AIM: To develop a safe, simple, noninvasive and affordable system to predict
      esophageal variceal bleeding (EVB) in decompensated cirrhosis patients. METHODS:
      Four hundred and eighty-six patients with decompensated cirrhosis (238 males and
      248 females), with a mean age of 63.1 +/- 11.2 years, were admitted to Changshu
      Affiliated Hospital of Suzhou University between May 2008 and March 2011.
      Patients enrolled in this study underwent ultrasound-Doppler (US-Doppler) to
      assess left gastric vein (LGV) blood flow velocity (LGVV) and blood flow
      direction (LGVBFD), and were evaluated by the Model For End-Stage Liver Disease
      (MELD) scoring system. All patients received follow-up evaluations every three
      months. The resulting data were entered into a database after each time point
      collection. RESULTS: Four hundred and sixteen patients completed follow-up
      evaluations for an average of 31.6 mo (range: 12 to 47 mo). Fifty-one (12.3%)
      patients experienced EVB. The change in the MELD score over three months
      (DeltaMELD), LGVV and LGVBFD were independently associated with EVB occurrence.
      MELD-US-Doppler Index (MUI), a new index, was developed and calculated using the
      following logistic regression equation: MUI = Logit (P) = 1.667 (DeltaMELD) +
      2.096 (LGVV) - 3.245 (LGVBFD) - 1.697. The area under the receiver operating
      characteristic curve for prediction of EVB occurrence was significantly higher
      for the MUI [0.858 (95%CI: 0.774-0.920)] than for DeltaMELD [0.734 (95%CI: 0.636
      0.817); P < 0.05], LGVV [0.679 (95%CI: 0.578-0.769); P < 0.05] or LGVBFD [0.726
      (95%CI: 0.627-0.810); P < 0.05] alone. When the MUI was set at 46, the index had
      high diagnostic accuracy (85.8%), with high specificity (80%) and sensitivity
      (87.27%). CONCLUSION: The MUI, a noninvasive and affordable index, can predict
      EVB occurrence in decompensated cirrhotic patients and serve as an alternative
      when conventional endoscopic screening is declined.

PMID- 24944494
TI  - Risk factors and therapeutic results of early local recurrence after
      transcatheter arterial chemoembolization.
AB  - AIM: To identify factors affecting early local recurrence after transcatheter
      arterial chemoembolization (TACE) and investigate treatments and outcomes for
      local recurrence. METHODS: Early local recurrence and no early local recurrence
      groups drawn from 134 patients who were initially diagnosed with hepatocellular
      carcinoma (HCC) and showed a complete response (CR) to TACE treatment between
      January 1, 2006, and January 31, 2012, were analyzed by univariate and
      multivariate analyses. Additionally, the subsequent treatment for patients with
      recurrence was analyzed, and in cases in which TACE had been performed, the
      cumulative recurrence rates were calculated using the Kaplan-Meier method and
      compared with those of the primary lesion. RESULTS: The 1-, 2-, and 3-year
      survival rates were 92.3%, 60.2%, and 39.8%, respectively, in the early local
      recurrence group, which were significantly lower than those in both the late
      local and no local recurrence groups (P < 0.001). On multivariate analyses, non
      compact lipiodol uptake, large tumor size, and an alpha-fetoprotein > 20 ng/mL
      after achieving a CR were significant predictors. When TACE was performed for
      early and late locally recurrent lesions, a CR was observed in 15 patients
      (41.7%) and 11 patients (78.6%), and the cumulative recurrence rates at 6, 12,
      and 24 mo were 17.9%, 43.3%, and 71.2%, respectively, which did not differ
      significantly from those after the first CR of 20.5%, 44.0%, and 58.6%,
      respectively (P = 0.639). CONCLUSION: Closer monitoring and active treatments
      must be provided to patients with risk factors for early local recurrence of HCC.

PMID- 24944495
TI  - Magnetic resonance cholangiopancreatography study of pancreaticobiliary
      maljunction and pancreaticobiliary diseases.
AB  - AIM: To discuss the imaging anatomy about pancreaticobiliary ductal union,
      occurrence rate of pancreaticobiliary maljunction (PBM) and associated diseases
      in a Chinese population by using magnetic resonance cholangiopancreatography
      (MRCP). METHODS: Data were collected from 694 patients who underwent MRCP from
      January 2010 to December 2012. Three hundred and ninety-three patients were male
      and 301 patients were female. The age range was 16-92 years old and the average
      age was 51.8 years. The recruitment indication of all cases was patients who had
      clinical symptoms, such as abdominal pain, jaundice, nausea and vomiting, which
      thus were clinically suspected as relative pancreaticobiliary diseases. All cases
      were examined by MRCP using single-shot fast spin-echo sequences. In order to
      obtain MRCP images, the maximum intensity projection was used. RESULTS: According
      to the anatomy of pancreaticobiliary ductal union based on our analysis of MRCP
      images, all cases were classified into normal type and abnormal type according to
      the position of pancreaticobiliary ductal union. The abnormal type could be
      further divided into P-B type, B-P type and the duodenum type. By analyzing the
      incidence of biliary stone and inflammation, pancreatitis, biliary duct tumors
      and pancreatic tumors between normal and abnormal types, significant differences
      existed. The abnormal group was more likely to suffer from pancreaticobiliary
      diseases. Comparing three different types of PBM that were associated with
      pancreaticobiliary diseases by using Fisher's method, the result showed that
      there was no significant difference in the incidence of biliary stones,
      cholecystitis and pancreatic tumors. The incidence of pancreatitis in B-P type
      and P-B type was higher than that in duodenum type; the incidence of biliary duct
      tumor in B-P type was higher than that in P-B type; the incidence of biliary duct
      tumor in duodenum type was lower than that in P-B type. The incidence of
      congenital choledochus dilatation in normal type and abnormal type was similar,
      and there was no significant difference between the two types. CONCLUSION: Types
      of PBM are closely related to the occurrence of pancreaticobiliary diseases. MRCP
      has important clinical value in the early diagnosis and preventive treatment of
      pancreaticobiliary diseases.

PMID- 24944496
TI  - Subclinical abnormal glucose tolerance is a predictor of death in liver
      cirrhosis.
AB  - AIM: To determine if subclinical abnormal glucose tolerance (SAGT) has influence
      on survival of non-diabetic patients with liver cirrhosis. METHODS: In total, 100
      patients with compensated liver cirrhosis and normal fasting plasma glucose were
      included. Fasting plasma insulin (FPI) levels were measured, and oral glucose
      tolerance test (OGTT) was performed. According to OGTT results two groups of
      patients were formed: those with normal glucose tolerance (NGT) and those with
      SAGT. Patients were followed every three months. The mean follow-up was 932 d
      (range of 180-1925). Survival was analyzed by the Kaplan-Meyer method, and
      predictive factors of death were analyzed using the Cox proportional hazard
      regression model. RESULTS: Of the included patients, 30 showed NGT and 70 SAGT.
      Groups were significantly different only in age, INR, FPI and HOMA2-IR. Patients
      with SAGT showed lower 5-year cumulated survival than NGT patients (31.7% vs
      71.6%, P = 0.02). Differences in survival were significant only after 3 years of
      follow-up. SAGT, Child-Pugh B, and high Child-Pugh and Model for End-Stage Liver
      Disease (MELD) scores were independent predictors of death. The causes of death
      in 90.3% of cases were due to complications related to liver disease. CONCLUSION:
      SAGT was associated with lower survival. SAGT, Child-Pugh B, and high Child-Pugh
      and MELD scores were independent negative predictors of survival.

PMID- 24944497
TI  - Correlations between skin lesions induced by anti-tumor necrosis factor-alpha and
      selected cytokines in Crohn's disease patients.
AB  - AIM: To investigate the correlation between the appearance of skin lesions and
      concentration of interleukin (IL)-17A, IL-23 and interferon-gamma (IFN-gamma) in
      Crohn's disease (CD) patients during anti-tumor necrosis factor-alpha (TNF-alpha)
      therapy METHODS: A prospective study included 30 adult patients with CD of
      Caucasian origin (19 men and 11 women; mean age +/- SD 32.0 +/- 8.6 years) during
      biological therapy with anti-TNF-alpha antibodies from January 2012 to March
      2013. Eighteen patients were treated with infliximab, seven with adalimumab and
      five with certolizumab. Inclusion criteria were exacerbation of the underlying
      disease, Crohn's Disease Activity Index over 300 and the ineffectiveness of
      previously used non-biological therapies. Patients with a history of psoriasis,
      atopic dermatitis and other autoimmune skin lesions were excluded from the study.
      The control group consisted of 12 healthy subjects. A diagnostic survey was
      carried out, blood tests and careful skin examination were performed, and the
      serum levels of IL-17, IL-23 and IFN-gamma were measured using an enzyme-linked
      immunosorbent assays technique. Dermatoses that have developed in the course of
      biological therapy in patients who had no pre-existing skin lesions of similar
      character were qualified as skin lesions induced by anti-TNF-alpha therapy.
      RESULTS: Skin manifestations occurred in 18 of CD patients during the anti-TNF
      alpha therapy (60%), in the average time of 10.16 +/- 3.42 mo following the
      beginning of the 52-wk treatment cycle. Skin lesions observed in CD patients
      during biological therapy included psoriasiform lesions (44.4%), and eczema forms
      lesions (22.2%). In CD patients with drug induced skin lesions significantly
      higher levels of hemoglobin (13.3 +/- 1.5 g/dL vs 10.8 +/- 1.9 g/dL, P = 0.018)
      and hematocrit (39.9% +/- 4.5% vs 34.3% +/- 5.4%, P = 0.01), as well as a
      significantly lower level of platelets (268 +/- 62 * 10(3)/MUL vs 408 +/- 239 *
      10(3)/MUL, P = 0.046) was observed compared with CD patients without skin
      manifestations. The concentrations of IL-17A and IL-23 in CD patients with skin
      lesions developed under anti-TNF-alpha therapy were significantly higher compared
      to those in patients without lesions (IL-17A: 39.01 +/- 7.03 pg/mL vs 25.71 +/-
      4.90 pg/mL, P = 0.00004; IL-23: 408.78 +/- 94.13 pg/mL vs 312.15 +/- 76.24 pg/mL,
      P = 0.00556). CONCLUSION: Skin lesions in CD patients during biological therapy
      may result from significantly increased concentrations of IL-17A and IL-23, which
      are strongly associated with TNF-alpha/Th1 immune pathways.

PMID- 24944498
TI  - Impairment of gastrointestinal quality of life in severely obese patients.
AB  - AIM: To investigate the common gastro-intestinal symptoms and quality of life in
      severely obese subjects. METHODS: We prospectively recruited 340 severely obese
      patients [mean age 30.5 +/- 7.8 years; mean body mass index (BMI) 42.9 +/- 6.1
      kg/m(2)] and 340 healthy persons (mean BMI 23.1 +/- 3.8 kg/m(2)) matched in sex,
      age, marriage and education. The quality of life was studied using a specific
      gastrointestinal quality of life index (GIQLI) questionnaire. The 36 items and
      four functional domains of the GIQLI were compared and analyzed between the
      groups. The possible correlation of GIQLI scores with specific clinical variables
      in severely obese patients was assessed by measuring Pearson's coefficient of
      correlation. RESULTS: The mean GIQLI score of severely obese patients was lower
      than the normal control group (108.5 +/- 17.1 vs 123.2 +/- 14.8, P < 0.01).
      Severely obese patients had decreased scores in the domains of general health,
      including physical (17.3 +/- 6.0 vs 22.4 +/- 3.1, P < 0.01), emotional (12.6 +/-
      4.3 vs 16.6 +/- 3.1, P < 0.01) and social function (14.7 +/- 3.9 vs 17.9 +/- 2.5,
      P < 0.01), and in the domain of gastrointestinal symptoms (63.9 +/- 6.7 vs 66.3
      +/- 7.2, P < 0.05). A significantly decreased score was found in nine items, and
      there was an increased score in one out of the 19 items in the domain of symptoms
      of the GIQLI questionnaire. The decreased score in the domain of symptoms was
      correlated with increasing glycosylated hemoglobin (HbA1c) levels. CONCLUSION:
      Severe obesity resulted in a significant impairment of the quality of life and
      caused specific gastrointestinal symptoms compared with normal controls. The
      development of gastrointestinal symptoms is correlated increasing HbA1c,
      suggesting that a poor control of hyperglycemia might be the etiology.

PMID- 24944499
TI  - Does hyoscine butylbromide really improve polyp detection during colonoscopy? A
      meta-analysis of randomized controlled trials.
AB  - AIM: To investigate the benefits of hyoscine butylbromide in polyp detection
      during colonoscopy by a meta-analysis of available randomized controlled trials
      (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and
      the Science Citation Index up to September 2013, were searched. The primary
      outcome was polyp detection rate, and the secondary outcome was adenoma detection
      rate. The meta-analysis was performed using the free software Review Manager.
      Differences observed between the treated and the control groups were expressed as
      odds ratio (OR) with a 95% confidence interval (CI). A fixed-effects model was
      used to pool data when statistical heterogeneity was absent. If statistical
      heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS:
      The initial search identified nine articles. After screening, five RCTs with a
      total of 1998 patients were included in this meta-analysis. Of the five studies,
      all described a comparison of baseline patient characteristics and showed that
      there was no statistically significant difference between the two groups. Among
      the 1998 patients, 1006 received hyoscine butylbromide and 992 were allocated to
      the control group, and the polyp detection rate was reported. There were no
      significant differences between the treated and the control group (OR = 1.09,
      95%CI: 0.91-1.31, P = 0.33). Four RCTs included 1882 patients, of whom 948
      received hyoscine butylbromide, and the adenoma detection rate was reported.
      There were no significant differences between the treated and the control group
      (OR = 1.13, 95%CI: 0.92-1.38, P = 0.24). CONCLUSION: The use of hyoscine
      butylbromide did not significantly improve the polyp detection rate during
      colonoscopy.

PMID- 24944500
TI  - Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde
      cholangiopancreatography pancreatitis in high-risk patients: a meta-analysis.
AB  - AIM: To assess the effectiveness of pancreatic stents for preventing pancreatitis
      in high-risk patients after endoscopic retrograde cholangiopancreatography
      (ERCP). METHODS: PubMed, Embase, Science Citation Index, and Cochrane Controlled
      Trials Register were searched to identify relevant trials published in English.
      Inclusion and exclusion criteria were used to screen for suitable studies. Two
      reviewers independently judged the study eligibility while screening the
      citations. The methodological quality of the included trials was assessed using
      the Jadad scoring system. All results were expressed as OR and 95%CI. Data were
      analyzed using Stata12.0 software. RESULTS: Ten eligible randomized controlled
      trials were selected, including 1176 patients. A fixed-effects model in meta
      analysis supported that pancreatic duct stents significantly decreased the
      incidence of post-ERCP pancreatitis (PEP) in high-risk patients (OR = 0.25;
      95%CI: 0.17-0.38; P < 0.001). Pancreatic stents also alleviated the severity of
      PEP (mild pancreatitis after ERCP: OR = 0.33; 95%CI: 0.21-0.54; P < 0.001;
      moderate pancreatitis after ERCP: OR = 0.30; 95%CI: 0.13-0.67; P = 0.004). The
      result of severe pancreatitis after ERCP was handled more rigorously (OR = 0.24;
      95%CI: 0.05-1.16; P = 0.077). Serum amylase levels were not different between
      patients with pancreatic stents and control patients (OR = 1.08; 95%CI: 0.82
      1.41; P = 0.586). CONCLUSION: Placement of prophylactic pancreatic stents may
      lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate
      the severity of this condition.

PMID- 24944502
TI  - Primary esophageal sclerosing mucoepidermoid carcinoma with "tissue
      eosinophilia".
AB  - Mucoepidermoid carcinoma (MEC) is a rare primary esophageal malignancy. It is
      characterized by poor clinical recognition, pre-operative diagnostic challenges
      and a lack of standardized therapeutic guidelines. We report the
      clinicopathological features of a hitherto unreported variant of esophageal MEC,
      sclerosing MEC with "tissue eosinophilia", in a mid-esophageal location in a 51
      year-old female. The diagnosis of the initial biopsy was challenging, because of
      the small size, poor orientation and inadequate representation of the MEC
      components. Recognition of the resectability of the tumor prompted surgical
      resection and enabled a demonstration of the low grade foci containing
      intermediate cells, mucin pools and the hitherto undescribed presence of stromal
      sclerosis and tissue eosinophils in esophageal MEC. Heightened
      clinicopathological awareness of esophageal MEC facilitated a definitive
      diagnosis and patient management. Increased recognition and global documentation
      of esophageal sclerosing MEC with "tissue eosinophilia" is necessary to improve
      the understanding and diagnosis of this malignancy in this location and to
      improve management guidelines. 

PMID- 24944503
TI  - Diagnosis and management of choledochal cyst: 20 years of single center
      experience.
AB  - We report the first case series from Africa and the Middle East on choledochal
      cyst, a disease which shows significant geographical distribution with high
      incidence in the Asian population. In this study, the epidemiological data of the
      patients are presented and analyzed. Attention was paid to diagnostic imaging and
      its accuracy in the diagnosis and classification of choledochal cyst. Most cases
      of choledochal cyst disease have type I and IV-A cysts according to the Todani
      classification system, which support the etiological theories of choledochal
      cyst, especially Babbitt's theory of the anomalous pancreaticobiliary duct
      junction, which are clearly stated. The difficulties and hazards of surgical
      management and methods used to avoid operative complications are clarified. Early
      and late postoperative complications are also included. This study should be
      followed by multicenter studies throughout Egypt to help assess the incidence of
      choledochal cysts in one of the largest populations in Africa and the Middle
      East.

PMID- 24944504
TI  - Fish bone migration to the urinary bladder after rectosigmoid colon perforation.
AB  - Fish bones are the most common foreign objects leading to bowel perforation. Most
      cases are confined to the extraluminal space without penetration of an adjacent
      organ. However, abscess formation due to the perforation of the rectosigmoid
      colon by a fish bone can lead to the penetration of the urinary bladder and may
      subsequently cause the fish bone to migrate into the urinary bladder. In the
      presented case, a 42-year-old female was admitted for lower abdominal pain. The
      computed tomography (CT) demonstrated a 5 cm pelvic abscess containing a thin and
      curvilinear foreign body. After conservative management, the patient was
      discharged. After 1 mo, the subject developed a mechanical ileus. Surgery had to
      be delayed due to her hyperthyroidism. Migration of the foreign body to the
      urinary bladder was shown on additional CT. A Yellowish fish bone 3.5 cm in size
      was removed through intra-operative cystoscopy. The patient was discharged 8 d
      after the operation without any unexpected event.

PMID- 24944501
TI  - Long-term durable response to lenalidomide in a patient with hepatic epithelioid
      hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma (EH) is a rare tumor arising from the vascular
      endothelial cells of soft tissue or visceral organs. The most common visceral
      site is the liver, where it is often involved in a multifocal manner known as
      hepatic EH (HEH). Surgical resection with curative intent represents the gold
      standard therapy. When surgery is not feasible, or in cases of metastatic
      disease, no standard medical treatment is currently indicated. In small series,
      drugs with anti-angiogenic activity (such as bevacizumab, sorafenib, thalidomide,
      and lenalidomide) have been proposed with promising results. We describe a 73
      year-old man with multifocal non-resectable HEH treated with lenalidomide.
      Disease status was evaluated by abdominal ultrasound and magnetic resonance every
      four months. The patient was treated for a total of 39 mo with prolonged disease
      stabilization and, at the time of writing, is still under treatment with a good
      tolerance profile. During a short period of treatment discontinuation, the
      disease showed slight progression that immediately resolved after the
      reintroduction of lenalidomide. Lenalidomide may represent a valid treatment
      option for HEH due to its anti-angiogenic and antineoplastic activities. This
      preliminary result merits further study in a large series. 

PMID- 24944505
TI  - Contributions of Therapist Characteristics and Stability to Intensive In-home
      Therapy Youth Outcomes.
AB  - OBJECTIVE: This study examines the influence of therapist and youth
      characteristics on post-discharge outcomes from intensive in-home therapy.
      METHOD: Data for 1,416 youth and 412 therapists were obtained from a behavioral
      health services provider. The Huber-White method was used to account for nested
      data; ordered logistic regression was employed to assess outcomes. RESULTS:
      Therapist gender and employment stability were significantly associated with
      youth outcomes. The likelihood of an undesirable outcome was significantly less
      for cases with female therapists. CONCLUSION: Findings underscore the need for
      additional study concerning the impact of therapist characteristics and stability
      on youth outcomes, and to improve the understanding of the relationship between
      the two. Future studies in these areas would advance social work practice in
      family-based treatment programs.

PMID- 24944506
TI  - 3D/2D Model-to-Image Registration for Quantitative Dietary Assessment.
AB  - Image-based dietary assessment is important for health monitoring and management
      because it can provide quantitative and objective information, such as food
      volume, nutrition type, and calorie intake. In this paper, a new framework, 3D/2D
      model-to-image registration, is presented for estimating food volume from a
      single-view 2D image containing a reference object (i.e., a circular dining
      plate). First, the food is segmented from the background image based on Otsu's
      thresholding and morphological operations. Next, the food volume is obtained from
      a user-selected, 3D shape model. The position, orientation and scale of the model
      are optimized by a model-to-image registration process. Then, the circular plate
      in the image is fitted and its spatial information is used as constraints for
      solving the registration problem. Our method takes the global contour information
      of the shape model into account to obtain a reliable food volume estimate.
      Experimental results using regularly shaped test objects and realistically shaped
      food models with known volumes both demonstrate the effectiveness of our method.

PMID- 24944507
TI  - Comparison of three methods of tonometry in normal subjects: Goldmann applanation
      tonometer, non-contact airpuff tonometer, and Tono-Pen XL.
AB  - OBJECTIVE: WE AIMED TO COMPARE INTRAOCULAR PRESSURE (IOP) MEASUREMENTS VIA THREE
      DIFFERENT TONOMETERS: the Goldmann applanation tonometer (GAT), the Tono-Pen((r))
      XL (TPXL), and a non-contact airpuff tonometer (NCT). METHODS: This was a cross
      sectional study of 200 eyes from 200 patients. Right eyes of all patients were
      included in this study. IOP was measured via GAT, NCT, and TPXL by three
      physicians. Each physician used one of the tonometers. Measurements via the three
      devices were compared. RESULTS: The mean IOP was 15.5+/-2.2 mmHg (range 10-22)
      with the GAT, 16.1+/-3.0 (range 9-25) with the TPXL, and 16.1+/-2.8 (range 10-26)
      with the NCT. Bland-Altman analysis showed that the mean difference between
      measurements from the NCT and the GAT was 0.6+/-2.3 mmHg. The mean difference
      between the TPXL and GAT measurements was 0.7+/-2.5 mmHg. The mean difference
      between the NCT and TPXL measurements was -0.02+/-3.0 mmHg. There was no
      significant difference between the groups according to a one-way analysis of
      variance (ANOVA) test. P-values were 0.998 for NCT-TPXL, 0.067 for NCT-GAT, and
      0.059 for TPXL-GAT. CONCLUSION: The NCT and TPXL provide IOP measurements
      comparable to those of the gold standard GAT in normotensive eyes.

PMID- 24944508
TI  - Optimization of biguanide derivatives as selective antitumor agents blocking
      adaptive stress responses in the tumor microenvironment.
AB  - Adaptive cellular responses resulting from multiple microenvironmental stresses,
      such as hypoxia and nutrient deprivation, are potential novel drug targets for
      cancer treatment. Accordingly, we focused on developing anticancer agents
      targeting the tumor microenvironment (TME). In this study, to search for
      selective antitumor agents blocking adaptive responses in the TME, thirteen new
      compounds, designed and synthesized on the basis of the arylmethylbiguanide
      scaffold of phenformin, were used in structure activity relationship studies of
      inhibition of hypoxia inducible factor (HIF)-1 and unfolded protein response
      (UPR) activation and of selective cytotoxicity under glucose-deprived stress
      conditions, using HT29 cells. We conducted luciferase reporter assays using
      stable cell lines expressing either an HIF-1-responsive reporter gene or a
      glucose-regulated protein 78 promoter-reporter gene, which were induced by
      hypoxia and glucose deprivation stress, respectively, to screen for TME-targeting
      antitumor drugs. The guanidine analog (compound 2), obtained by bioisosteric
      replacement of the biguanide group, had activities comparable with those of
      phenformin (compound 1). Introduction of various substituents on the phenyl ring
      significantly affected the activities. In particular, the o-methylphenyl analog
      compound 7 and the o-chlorophenyl analog compound 12 showed considerably more
      potent inhibitory effects on HIF-1 and UPR activation than did phenformin, and
      excellent selective cytotoxicity under glucose deprivation. These compounds,
      therefore, represent an improvement over phenformin. They also suppressed HIF-1-
      and UPR-related protein expression and secretion of vascular endothelial growth
      factor-A. Moreover, these compounds exhibited significant antiangiogenic effects
      in the chick chorioallantoic membrane assay. Our structural development studies
      of biguanide derivatives provided promising candidates for a novel anticancer
      agent targeting the TME for selective cancer therapy, to be subjected to further
      in vivo study. 

PMID- 24944509
TI  - Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast
      cancer using in vitro and in vivo models.
AB  - To date, plants have been the major source of anticancer drugs. Boldine is a
      natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this
      study, we found that boldine potently inhibited the viability of the human
      invasive breast cancer cell lines, MDA-MB-231 (48-hour IC50 46.5+/-3.1 MUg/mL)
      and MDA-MB-468 (48-hour IC50 50.8+/-2.7 MUg/mL). Boldine had a cytotoxic effect
      and induced apoptosis in breast cancer cells as indicated by a higher amount of
      lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In
      addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase.
      The anticancer mechanism is associated with disruption of the mitochondrial
      membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively
      induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found
      that boldine could inhibit nuclear factor kappa B activation, a key molecule in
      tumor progression and metastasis. In addition, protein array and Western blotting
      analysis showed that treatment with boldine resulted in downregulation of Bcl-2
      and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An
      acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body
      weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or
      100 mg/kg) significantly reduced tumor size in an animal model of breast cancer.
      Our results suggest that boldine is a potentially useful agent for the treatment
      of breast cancer.

PMID- 24944510
TI  - The new concepts on overcoming drug resistance in lung cancer.
AB  - Lung cancer is one of the most deadly diseases worldwide. The current first-line
      therapies include chemotherapy using epidermal growth factor receptor tyrosine
      kinase inhibitors and radiotherapies. With the current progress in identifying
      new molecular targets, acquired drug resistance stands as an obstacle for good
      prognosis. About half the patients receiving epidermal growth factor receptor
      tyrosine kinase inhibitor treatments develop resistance. Although extensive
      studies have been applied to elucidate the underlying mechanisms, evidence is far
      from enough to establish a well-defined picture to correct resistance. In the
      review, we will discuss four different currently developed strategies that have
      the potential to overcome drug resistance in lung cancer therapies and facilitate
      prolonged anticancer effects of the first-line therapies. 

PMID- 24944511
TI  - Continuing to Confront COPD International Patient Survey: methods, COPD
      prevalence, and disease burden in 2012-2013.
AB  - PURPOSE: The Continuing to Confront COPD International Patient Survey aimed to
      estimate the prevalence and burden of COPD globally and to update findings from
      the Confronting COPD International Survey conducted in 1999-2000. MATERIALS AND
      METHODS: Chronic obstructive pulmonary disease (COPD) patients in 12 countries
      worldwide were identified through systematic screening of population samples.
      Telephone and face-to-face interviews were conducted between November 2012 and
      May 2013 using a structured survey that incorporated validated patient-reported
      outcome instruments. Eligible patients were adults aged 40 years and older who
      were taking regular respiratory medications or suffered with chronic respiratory
      symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a
      physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of
      chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test
      (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. RESULTS: Of
      106,876 households with at least one person aged >=40 years, 4,343 respondents
      fulfilled the case definition of COPD and completed the full survey. COPD
      prevalence ranged from 7% to 12%, with most countries falling within the range of
      7%-9%. In all countries, prevalence increased with age, and in all countries
      except the US was greater among men (range 6%-14%) than among women (range 5%
      11%). A significant disease burden was observed when considering COPD symptoms or
      health status, and showed wide variations across countries. Prevalence of
      moderate-to-severe dyspnea (mMRC scale >=2) ranged from 27% to 61%, and mean CAT
      score ranged from 16.0 to 24.8, indicating medium-to-high impairment. CONCLUSION:
      This survey, representing 12 countries, showed similar rates of estimated COPD
      prevalence across countries that were higher than those reported a decade ago in
      the original Confronting COPD International Survey. A significant burden of COPD
      was demonstrated by symptoms and health care-resource use, similar to that
      reported in the original survey.

PMID- 24944512
TI  - Detection of PLGA-based nanoparticles at a single-cell level by synchrotron
      radiation FTIR spectromicroscopy and correlation with X-ray fluorescence
      microscopy.
AB  - Poly-lactide-co-glycolide (PLGA) is one of the few polymers approved by the US
      Food and Drug Administration as a carrier for drug administration in humans;
      therefore, it is one of the most used materials in the formulation of polymeric
      nanoparticles (NPs) for therapeutic purposes. Because the cellular uptake of
      polymeric NPs is a hot topic in the nanomedicine field, the development of
      techniques able to ensure incontrovertible evidence of the presence of NPs in the
      cells plays a key role in gaining understanding of their therapeutic potential.
      On the strength of this premise, this article aims to evaluate the application of
      synchrotron radiation-based Fourier transform infrared spectroscopy (SR-FTIR)
      spectromicroscopy and SR X-ray fluorescence (SR-XRF) microscopy in the study of
      the in vitro interaction of PLGA NPs with cells. To reach this goal, we used PLGA
      NPs, sized around 200 nm and loaded with superparamagnetic iron oxide NPs (PLGA
      IO-NPs; Fe3O4; size, 10-15 nm). After exposing human mesothelial (MeT5A) cells to
      PLGA-IO-NPs (0.1 mg/mL), the cells were analyzed after fixation both by SR-FTIR
      spectromicroscopy and SR-XRF microscopy setups. SR-FTIR-SM enabled the detection
      of PLGA NPs at single-cell level, allowing polymer detection inside the
      biological matrix by the characteristic band in the 1,700-2,000 cm(-1) region.
      The precise PLGA IR-signature (1,750 cm(-1) centered pick) also was clearly
      evident within an area of high amide density. SR-XRF microscopy performed on the
      same cells investigated under SR-FTIR microscopy allowed us to put in evidence
      the Fe presence in the cells and to emphasize the intracellular localization of
      the PLGA-IO-NPs. These findings suggest that SR-FTIR and SR-XRF techniques could
      be two valuable tools to follow the PLGA NPs' fate in in vitro studies on cell
      cultures.

PMID- 24944514
TI  - A new method for analyzing auditory brain-stem response waveforms using a moving
      minimum subtraction procedure of digitized analog recordings.
AB  - The auditory brain-stem response (ABR) waveform comprises a set of waves (labeled
      I-VII) recorded with scalp electrodes over 10 ms after an auditory stimulation
      with a brief click sound. Quite often, the waves are fused (confluent) and
      baseline-irregular and sloped, making wave latencies and wave amplitudes
      difficult to establish. In the present paper, we describe a method, labeled
      moving-minimum subtraction, based on digitization of the analog ABR waveform (154
      data points/ms) in order to achieve alignment of the ABR response to a straight
      baseline, often with clear baseline separation of waves and resolution of fused
      waves. Application of the new method to groups of patients showed marked
      differences in ABR waveforms between patients with schizophrenia versus patients
      with adult attention deficit/hyperactivity disorder versus healthy controls. The
      findings show promise regarding the possibility to identify ABR markers to be
      used as biomarkers as support for clinical diagnoses of these and other
      neuropsychiatric disorders. 

PMID- 24944515
TI  - The relationships of self-efficacy, physical activity, and paid work to health
      related quality of life among patients with chronic obstructive pulmonary disease
      (COPD).
AB  - PURPOSE: Although chronic obstructive pulmonary disease (COPD) primarily affects
      the lungs, it is regarded as a systemic disorder associated with comorbidity and
      physical deterioration, which often results in reduced levels of health-related
      quality of life (HRQoL). Self-efficacy is an important concept in self
      management, which is vital for improving HRQoL in patients with COPD. The purpose
      of this study was to examine how general self-efficacy, leisure time physical
      activity, and sociodemographic variables such as employment status are related to
      the physical and mental health components of HRQoL in patients with COPD.
      PATIENTS AND METHODS: In this cross-sectional study, 97 COPD patients (54.6%
      male, mean age 64.6 years, standard deviation [SD] 9.5) beginning a pulmonary
      rehabilitation program completed three self-report questionnaires: the short form
      (SF)-12v2 Health Survey as a measure of HRQoL; the General Self-Efficacy Scale;
      and a standardized instrument measuring regular leisure time physical activity.
      RESULTS: The physical health component median score was 31.3 (interquartile range
      [IQR] 16.3) and the mental health component median score was 45.9 (IQR 21.5). Two
      sets of linear regression analyses were performed, one predicting physical health
      and the other predicting mental health. The first analysis showed that better
      physical health was directly related to being in paid work (P-value <0.001), but
      was not significantly related to age, sex, marital status, education, work
      status, physical activity, or self-efficacy. In the second analysis, better
      mental health was directly related to living with a partner, being physically
      active, and having higher self-efficacy (P-value <0.001). CONCLUSION: The
      findings suggest that general self-efficacy has differential relationships to the
      two dimensions of HRQoL. Our results indicate that general self-efficacy,
      physical activity, and paid work might be important factors for improving HRQoL
      of persons with COPD, and should be taken into consideration in pulmonary
      rehabilitation.

PMID- 24944513
TI  - Sequential optimization of methotrexate encapsulation in micellar nano-networks
      of polyethyleneimine ionomer containing redox-sensitive cross-links.
AB  - A functional polycation nanonetwork was developed for delivery of water soluble
      chemotherapeutic agents. The complexes of polyethyleneimine grafted methoxy
      polyethylene glycol (PEI-g-mPEG) and Zn(2+) were utilized as the micellar
      template for cross-linking with dithiodipropionic acid, followed by an acidic pH
      dialysis to remove the metal ion from the micellar template. The synthesis method
      was optimized according to pH, the molar ratio of Zn(2+), and the cross-link
      ratio. The atomic force microscopy showed soft, discrete, and uniform nano
      networks. They were sensitive to the simulated reductive environment as
      determined by Ellman's assay. They showed few positive zeta potential and an
      average hydrodynamic diameter of 162+/-10 nm, which decreased to 49+/-11 nm upon
      dehydration. The ionic character of the nano-networks allowed the achievement of
      a higher-loading capacity of methotrexate (MTX), approximately 57% weight per
      weight, depending on the cross-link and the drug feed ratios. The nano-networks
      actively loaded with MTX presented some suitable properties, such as the
      hydrodynamic size of 117+/-16 nm, polydispersity index of 0.22, and a prolonged
      swelling-controlled release profile over 24 hours that boosted following
      reductive activation of the nanonetwork biodegradation. Unlike the PEI ionomer,
      the nano-networks provided an acceptable cytotoxicity profile. The drug-loaded
      nano-networks exhibited more specific cytotoxicity against human hepatocellular
      carcinoma cells if compared to free MTX at concentrations above 1 MUM. The
      enhanced antitumor activity in vitro might be attributed to endocytic entry of
      MTX-loaded nano-networks that was found in the epifluorescence microscopy
      experiment for the fluorophore-labeled nano-networks. 

PMID- 24944516
TI  - Critical appraisal of sorafenib in the treatment of Chinese patients with renal
      cell carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for 3% of all malignancies, and is the most
      aggressive cancer of the genitourinary system. Metastatic RCC is naturally
      resistant to chemotherapy and radiotherapy, and immunotherapy is of little
      benefit. In recent years, the emergence of molecular-targeted therapies has
      largely changed the therapeutic approach to metastatic RCC. These novel
      multikinase inhibitors have now become first-choice therapy because of their
      activity in inhibiting both cell proliferation and tumor angiogenesis. Sorafenib
      is the first tyrosine kinase inhibitor found to be effective in treating patients
      with metastatic RCC. Due to its good efficacy and safety, this agent is
      recommended as both first-line and second-line therapy for metastatic RCC in the
      People's Republic of China. Sorafenib seems to be more effective in patients of
      Chinese ethnicity than in western patients, and is well tolerated with a
      manageable toxicity profile, even at higher dosages and when used in combination
      with other anticancer agents. Novel biomarkers for predicting the efficacy of
      sorafenib have potential clinical value for guiding individualized targeted
      therapy. 

PMID- 24944517
TI  - Critical appraisal of pemetrexed in the treatment of NSCLC and metastatic
      pulmonary nodules.
AB  - Pemetrexed, a new multitarget antifolate antineoplastic agent, has significantly
      improved the overall survival in nonsquamous non-small-cell lung cancer patients.
      Presently, pemetrexed is recommended for first line treatment in combination with
      platinum derivatives, for second line treatment as a single agent and, more
      recently, as maintenance treatment after first line chemotherapy. In this article
      we critically appraise the status of pemetrexed including pharmacodynamics,
      pharmacokinetics, toxicity, and the cost effectiveness of pemetrexed, as well as
      the predictive biomarkers for pemetrexed based chemotherapy. 

PMID- 24944518
TI  - Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a
      downregulator of 5alpha-reductase activity pathways in prostatic epithelial
      cells.
AB  - DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study,
      we used prostate cancer (PC)-3 as the cell line to study the effects of DLBS4847
      on prostatic cell viability, as well as related molecular changes associated with
      the decreased cell number. The observation revealed that DLBS4847 inhibited the
      growth of PC3 cells through downregulation of the 5alpha-reductase (5AR) pathway.
      At the transcription level, 5AR1 and androgen-receptor gene expressions were
      downregulated in a dose-dependent manner. Furthermore, 5AR-1 and
      dihydrotestosterone expression were also downregulated at the protein level. A
      microarray study was also performed to see the effects of DLBS4847 on
      differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847
      downregulated genes related to prostate growth and hypertrophy. Our results
      suggested that DLBS4847 could potentially become an alternative treatment for
      prostate disorders, such as benign prostatic hyperplasia. In this regard,
      DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR
      pathway. 

PMID- 24944519
TI  - Environmental exposure assessment framework for nanoparticles in solid waste.
AB  - Information related to the potential environmental exposure of engineered
      nanomaterials (ENMs) in the solid waste management phase is extremely scarce. In
      this paper, we define nanowaste as separately collected or collectable waste
      materials which are or contain ENMs, and we present a five-step framework for the
      systematic assessment of ENM exposure during nanowaste management. The framework
      includes deriving EOL nanoproducts and evaluating the physicochemical properties
      of the nanostructure, matrix properties and nanowaste treatment processes as well
      as transformation processes and environment releases, eventually leading to a
      final assessment of potential ENM exposure. The proposed framework was applied to
      three selected nanoproducts: nanosilver polyester textile, nanoTiO2 sunscreen
      lotion and carbon nanotube tennis racquets. We found that the potential global
      environmental exposure of ENMs associated with these three products was an
      estimated 0.5-143 Mg/year, which can also be characterised qualitatively as
      medium, medium, low, respectively. Specific challenges remain and should be
      subject to further research: (1) analytical techniques for the characterisation
      of nanowaste and its transformation during waste treatment processes, (2)
      mechanisms for the release of ENMs, (3) the quantification of nanowaste amounts
      at the regional scale, (4) a definition of acceptable limit values for exposure
      to ENMs from nanowaste and (5) the reporting of nanowaste generation data.

PMID- 24944520
TI  - Critical experimental parameters related to the cytotoxicity of zinc oxide
      nanoparticles.
AB  - The increasing use of zinc oxide nanoparticles (ZnO-NPs) has raised concerns
      about their potential hazards to human and environmental health. In this study,
      the characterization and cytotoxicity of two ZnO-NPs products (Z-COTE and Z-COTE
      HP1) were investigated. The zinc content of Z-COTE and Z-COTE HP1 was 82.5 +/-
      7.3 and 80.1 +/- 3.5 %, respectively. Both ZnO-NP samples contained sub-cytotoxic
      levels of iron and copper, and silicon was detected from the surface coating of Z
      COTE HP1. All samples were highly agglomerated, and the primary particles
      appeared as variable polyhedral structures. There was no significant difference
      in size distribution or average diameter of Z-COTE (53 +/- 23 nm) and Z-COTE HP1
      (54 +/- 26 nm). A dose-dependent cytotoxicity was observed 24 h after exposure to
      ZnO-NPs, and monocytes were more sensitive than lung epithelial cells or
      lymphoblasts in both human and mouse cells. There was a significant difference in
      cytotoxicity between nano- and fine-forms, but only at the threshold cytotoxic
      dose with cellular metabolism assays. Compared to uncoated ZnO-NPs, the surface
      coating with triethoxycaprylylsilane marginally attenuated cellular oxidative
      stress and protected cellular metabolic activity. These results demonstrate the
      importance of model cell type, dose selection, and cytotoxicity assessment
      methodology to accurately evaluate the potential toxicity of various
      nanoparticles in vitro.

PMID- 24944521
TI  - The Construction of All-Carbon Quaternary Stereocenters by Use of Pd-Catalyzed
      Asymmetric Allylic Alkylation Reactions in Total Synthesis.
AB  - All-carbon quaternary stereocenters have posed significant challenges in the
      synthesis of complex natural products. These important structural motifs have
      inspired the development of broadly applicable palladium-catalyzed asymmetric
      allylic alkylation reactions of unstabilized non-biased enolates for the
      synthesis of enantioenriched alpha-quaternary products. This microreview outlines
      key considerations in the application of palladium-catalyzed asymmetric allylic
      alkylation reactions and presents recent total syntheses of complex natural
      products that have employed these powerful transformations for the direct,
      catalytic, enantioselective construction of all-carbon quaternary stereocenters.

PMID- 24944523
TI  - Expression of Derlin-1 and its effect on expression of autophagy marker genes
      under endoplasmic reticulum stress in lung cancer cells.
AB  - BACKGROUND: Recent findings indicated that Derlin-1 has an important function in
      tumour progression. In this study, we aimed to determine whether Derlin-1 has an
      oncogene function as a cross-talk molecule with autophagy. METHODS: Cancer cells
      were treated with tunicamycin (TM) for 8 and 24 h. The expression of Derlin-1 and
      autophagy-related genes was determined by western blot. Autophagy was analysed by
      fluorescence microscopy after staining the cancer cells with
      monodansylcadaverine. The interaction between Derlin-1 and other proteins was
      identified using co-immunoprecipitation assay. RESULTS: Our study demonstrated
      high Derlin-1 expression levels in most non-small lung cancer cell lines. Derlin
      1 expression was enhanced under endoplasmic reticulum (ER) stress. Previous
      studies revealed that TM triggers the initiation of autophagy by activating
      Beclin 1, converting LC3I to LC3II and degrading p62. Knockdown of Derlin-1 did
      not affect Beclin 1 and LC3II expression but disrupted the degradation of p62
      under ER stress, which resulted in the blockage of autophagy flux. Furthermore,
      Derlin-1 and p62 were observed to interact under ER stress. CONCLUSION: This
      study is the first report about the interaction between Derlin-1 and p62. Derlin
      1 may function in tumour progression partially by interacting with p62.

PMID- 24944522
TI  - Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill
      patients.
AB  - BACKGROUND: Transcranial Doppler can detect cerebral perfusion alteration in
      septic patients. We correlate static Transcranial Doppler findings with clinical
      signs of sepsis-associated encephalopathy. METHODS: Forty septic patients were
      examined with Transcranial Doppler on the first and third day of sepsis
      diagnosis. The pulsatility index (PI) and cerebral blood flow index (CBFi) were
      calculated by blood velocity in the middle cerebral artery (cm/sec). Patients
      underwent a daily cognitive assessment with the Confusion Assessment Method for
      the Intensive Care Unit (CAM-ICU) test. RESULTS: Twenty-one patients (55%) were
      found to present confusion. The majority of the patients presented a PI > 1.1
      (76%). PI on the first day (but not the third day) could predict a positive CAM
      ICU test in septic patients (PI cut-off: 1.3, AUC: 0.905, p < 0.01, sensitivity:
      95%, specificity: 88%, AUC: 0.618, p = 0.24). Multivariable analysis showed that
      PI on the first day is related to a positive CAM-ICU test independent of age and
      APACHE II score (OR: 5.6, 95% CI: 1.1-29, p = 0.03). A decrease of the PI on the
      third day was observed in the group that presented initially high PI (>1.3) (2.2
      +/- 0.71 vs. 1.81 +/- 0.64; p = 0.02). On the other hand, an increase in PI was
      observed in the other patients (1.01 +/- 0.15 vs. 1.58 +/- 0.57; p < 0.01). On
      only the first day, the mean blood velocity in the middle cerebral artery and
      CBFi were found to be lower in those patients with a high initial PI (36 +/- 21
      vs. 62 +/- 28 cm/sec; p < 0.01, 328 +/- 101 vs. 581 +/- 108; p < 0.01,
      respectively). CONCLUSIONS: Cerebral perfusion disturbance observed with
      Transcranial Doppler could explain clinical symptoms of sepsis-associated
      encephalopathy.

PMID- 24944524
TI  - Recovery of brain biomarkers following peroxisome proliferator-activated receptor
      agonist neuroprotective treatment before ischemic stroke.
AB  - BACKGROUND: Lipid lowering agent such as agonists of peroxisome proliferator
      activated receptors (PPAR) are suggested as neuroprotective agents and may
      protect from the sequelae of brain ischemic stroke. Although the demonstration is
      not clearly established in human, the underlying molecular mechanism may be of
      interest for future therapeutic purposes. To this end, we have used our well
      established rodent model of ischemia-reperfusion pre-treated or not with
      fenofibrate or atorvastatin and performed a differential proteomics analyses of
      the brain and analysed the protein markers which levels returned to "normal"
      following pre-treatments with PPARalpha agonists. RESULTS: In order to identify
      potential therapeutic targets positively modulated by pre-treatment with the
      PPARalpha agonists, two-dimensional gel electrophoresis proteome profiles between
      control, ischemia-reperfusion and pre-treated or not, were compared. The
      polypeptide which expression was altered following ischemia - reperfusion but
      whose levels remain unchanged after pre-treatment were characterized by mass
      spectrometry and further investigated by Western-blotting and
      immunohistochemistry. A series of 28 polypeptides were characterized among which
      the protein disulfide isomerase reduction - a protein instrumental to the
      unfolded protein response system - was shown to be reduced following PPARalpha
      agonists treatment while it was strongly increased in ischemia-reperfusion.
      CONCLUSIONS: Pre-treatment with PPARalpha agonist or atorvastatin show potential
      neuroprotective effects by inhibiting the PDI overexpression in conjunction with
      the preservation of other neuronal markers, several of which are associated with
      the regulation of protein homeostasis, signal transduction and maintenance of
      synaptic plasticity. This proteomic study therefore suggests that neuroprotective
      effect of PPARalpha agonists supposes the preservation of the expression of
      several proteins essential for the maintenance of protein homeostasis not
      necessarily directly linked to PPARalpha known-regulated targets.

PMID- 24944525
TI  - Inflammation: an important parameter in the search of prostate cancer biomarkers.
AB  - BACKGROUND: A more specific and early diagnostics for prostate cancer (PCa) is
      highly desirable. In this study, being inflammation the focus of our effort,
      serum protein profiles were analyzed in order to investigate if this parameter
      could interfere with the search of discriminating proteins between PCa and benign
      prostatic hyperplasia (BPH). METHODS: Patients with clinical suspect of PCa and
      candidates for trans-rectal ultrasound guided prostate biopsy (TRUS) were
      enrolled. Histological specimens were examined in order to grade and classify the
      tumor, identify BPH and detect inflammation. Surface Enhanced Laser
      Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) and two
      dimensional gel electrophoresis (2-DE) coupled with Liquid Chromatography-MS/MS
      (LC-MS/MS) were used to analyze immuno-depleted serum samples from patients with
      PCa and BPH. RESULTS: The comparison between PCa (with and without inflammation)
      and BPH (with and without inflammation) serum samples by SELDI-ToF-MS analysis
      did not show differences in protein expression, while changes were only observed
      when the concomitant presence of inflammation was taken into consideration. In
      fact, when samples with histological sign of inflammation were excluded, 20
      significantly different protein peaks were detected. Subsequent comparisons (PCa
      with inflammation vs PCa without inflammation, and BPH with inflammation vs BPH
      without inflammation) showed that 16 proteins appeared to be modified in the
      presence of inflammation, while 4 protein peaks were not modified. With 2-DE
      analysis, comparing PCa without inflammation vs PCa with inflammation, and BPH
      without inflammation vs the same condition in the presence of inflammation, were
      identified 29 and 25 differentially expressed protein spots, respectively.
      Excluding samples with inflammation the comparison between PCa vs BPH showed 9
      unique PCa proteins, 4 of which overlapped with those previously identified in
      the presence of inflammation, while other 2 were new proteins, not identified in
      our previous comparisons. CONCLUSIONS: The present study indicates that
      inflammation might be a confounding parameter during the proteomic research of
      candidate biomarkers of PCa. These results indicate that some possible biomarker
      candidate proteins are strongly influenced by the presence of inflammation, hence
      only a well-selected protein pattern should be considered for potential marker of
      PCa.

PMID- 24944526
TI  - Sensitivity and specificity of procalcitonin to determine etiology of diarrhea in
      children younger than 5 years.
AB  - AIM: The aim of this study is to assess the sensitivity and specificity of
      procalcitonin to determine bacterial etiology of diarrhea. THE EXAMINEES AND
      METHODS: For this purpose we conducted the study comprising 115 children aged 1
      to 60 months admitted at the Department of Pediatric Gastroenterology, Pediatric
      Clinic, divided in three groups based on etiology of the diarrhea that has been
      confirmed with respective tests during the hospitalization. Each group has equal
      number of patients - 35. The first group was confirmed to have bacterial
      diarrhea, the second viral diarrhea and the third extra intestinal diarrhea. The
      determination of procalcitonin has been established with the ELFA methods of
      producer B.R.A.H.M.S Diagnostica GmbH, Berlin, (Germany). RESULTS: From the total
      number of 1130 patient with acute diarrhea procalcitonin was assessed in 105. 67
      (63.8%) of these patient were male. More than one third (38.14%) of the children
      in our study were younger then 12 months. Approximately the same was the number
      of children 13-24 months (33 patients or 31.43%) and 25-60 months (32 patients or
      30.43%). The mean value of PRC in children with viral diarrhea was 0.13+/-0.5
      ng/mL in children with bacterial diarrhea was 5.3+/-4.9 ng/m Land in children
      with extra intestinal diarrhea was 1.7+/-2.8 ng/mL. When measured using ANOVA and
      Turkey HSD tests, results have shown the statistical significance when comparing
      viral with bacterial and extra intestinal diarrhea but were statistically
      insignificant when comparing bacterial and extra intestinal diarrhea. CONCLUSION:
      Procalcitonin is an important but not conclusive marker of bacterial etiology of
      acute diarrhea in children younger than 5 years.

PMID- 24944527
TI  - Respiratory complications from acute corrosive poisonings in adults.
AB  - INTRODUCTION: Acute corrosive poisonings are caused by ingestion of corrosive
      chemicals which are most commonly used as household agents. Intoxications with
      these kind of agents produce numerous and severe post-corrosive complications of
      the upper gastrointestinal tract. On the other hand, our experience showed that
      corrosive agents may also cause injuries of the respiratory system, which makes
      the treatment very hard and additionally complicates the severe clinical
      condition of the patient. OBJECTIVE: The aim of the study is to show the
      incidence of respiratory complications in acute corrosive poisonings, the need of
      various clinical investigations and also the treatment and final outcome of these
      kind of poisoning. METHODS: We retrospectively analyzed clinical records of 415
      patients hospitalized and treated at the University clinic for toxicology and
      urgent internal medicine, in Skopje, Republic of Macedonia, in the period between
      2007 and 2011. The protocol consisted of methods for analyzing the systemic
      complications, with an accent on the post-corrosive respiratory complications.
      RESULTS: From the total number of patients even 98 (23.61%) exhibited systemic
      complications, from which 51 (52.04%) are respiratory complications. The majority
      of patients are female (n=40, 78.43%) and the most common complication is
      pneumonia (n=47). The youngest patient in this study was 14 and the oldest was 87
      years old. CONCLUSION: Besides the gastrointestinal complications in the acute
      corrosive poisonings respiratory complications are also very often. They
      complicate the clinical state of patient and very often lead to fatal endings.

PMID- 24944528
TI  - From immigrant to patient: experiences of bosnian immigrants in the Swedish
      healthcare system.
AB  - BACKGROUND: We aimed to explore the background of refugees emigrating to Sweden
      and their situation in the new country with special focus on their contacts with
      the Swedish healthcare system. MATERIAL AND METHODS: Our study has a qualitative
      design. Data was collected between January and October 2013 during face-to-face
      interviews using open-ended questions. A qualitative content analysis was carried
      out in accordance with the Graneheim and Lundman method (2004). The participants
      were 8 women and 7 men, aged between 65 and 86 years who had emigrated from
      Bosnia and Herzegovina. They had lived in Sweden between 13 and 21 years.
      RESULTS: The findings revealed that the participants themselves experienced that
      change of scenery, culture and language influenced their own well-being. The most
      important finding was that language and communication difficulties are
      experienced as the major problems. These difficulties implied that all informants
      were forced to seek help from their children or to use an interpreter when they
      visited various healthcare institutions. CONCLUSIONS: Health care professionals
      need to be aware of the diverse needs of various ethnic groups in Sweden, some of
      whom may carry traumatic experiences that could influence their health. In order
      to provide trans cultural care, a professional staff needs to know that
      historical, political and socioeconomic factors may influence ethnic minorities.
      Health care staff needs to recognize that social problems might be medicalized.
      In particular this article emphasizes the problems associated with language.

PMID- 24944529
TI  - Frequency of L-SIL and H-SIL Findings in HPV Positive Women.
AB  - INTRODUCTION: Cervical carcinoma is one of the leading health issues for women
      throughout the world. In 90% of the cases cervical carcinoma develops after
      development of invasive lesions of the uterine cervix or 10-15 years before they
      are diagnosed using cytological screening-Papanicolau test. Infection with human
      papilloma virus is considered to be the basic etiological cause of development of
      CIN and cervical carcinoma. GOAL: Of this research was to determine frequency and
      type of abnormal cytological results in HPV positive and HPV negative patients.
      MATERIAL AND METHODS: Research is descriptive analytical, comparative and partly
      epidemiological, of mostly clinically applicable character. Used data included
      information on total number of examinations, type of exam, results of cytological
      and pathohistological diagnostics, HPV findings in cervix smear and HPV type in
      the period between January 1, 2009 and December 31, 2011. RESULTS: During the
      period of analysis total number of Pap tests was 6376 (43.33%), in comparison to
      other exams 7828 (56.67%). For this period total number of L-SIL and H-SIL (PAPA
      III) was 395 (6.20%), in comparison to other results 5894 (92.44%). After
      analysis largest subset of HPV positive patients had pathohistological diagnosis
      of CIN I that is 250 (43.10%) of them, then CIN II with 162 (27.93%) patients,
      CIN III with 149 (25.69) and 3 (0.52%) patients had CIS while 16 (2.76%) had a
      clear test result. We can conclude there is a statistically significant margin of
      frequency between positive HPV results in relation to diagnosis. Highest
      percentage of L-SIL and H-SIL (PAPA III) test results was in 2010 and was 9.5%,
      and lowest in 2009 with 4.34%. Largest number of patients, 43.0%, with HPV
      positive results after cervical smear had pathohistological diagnosis of CIN I.

PMID- 24944530
TI  - Influence of body weight on the biochemical indicators in menopause.
AB  - INTRODUCTION: One of the problems of today and probably this century is obesity,
      which is classified by the WHO as a disease. MATERIAL AND METHODS: We performed a
      prospective cross-sectional study of the body weight impact on certain
      biochemical indicators in menopausal women living in the municipalities Cazin and
      Velika Kladusa. RESULTS AND DISCUSSION: The study included 334 women aged 40-60
      years, who had regular medical examinations. For each patient at the beginning of
      the study we measured: body mass index, total cholesterol values, LDL, HDL and
      triglycerides fractions. Our findings indicate an increase in total cholesterol,
      LDL fraction and triglycerides in patients with increased body mass index,
      without statistical significance. Values of HDL fraction were significantly
      decreased with increasing body mass index.

PMID- 24944531
TI  - Knowledge About Spread of HIV Infection Among Dentists Employed in Private and
      State Practice.
AB  - INTRODUCTION: Lack of knowledge of how an infection is spread and how to control
      the infection in dental medicine indicates that there is possibility of more
      spreading and that dental medicine requires more education about this problem.
      MATERIAL AND METHODS: Research conducted in period of May and July as a study of
      random selection from 271 workers in dental medicine from Canton Sarajevo: 147
      dentists employed in public health care and 124 employed in private sector.
      RESULTS: Results show that dentists employed in private sector have more
      knowledge about HIV infection spread than those employed in public sector of
      dental medicine(t=-2,82, p=0,005). Research have shown that dentists who have
      less then 10 years of experience know more about HIV spread than dentist with
      more work experience (F=6,377, p=0,000). CONCLUSION: We think that is essential
      to work on expending knowledge on blood transmitted pathogens with all medical
      workers and especially those that are most exposed like dentists.

PMID- 24944532
TI  - Relation between near work and myopia progression in student population.
AB  - AIM: To determine relation between near work and myopia progression in student
      population. Causes of myopia occurrence are not sufficiently explained. METHODS:
      This retrospective-prospective, descriptive research included 100 students with
      verified myopia up to -3 Dsph. Ophthalmological examination and measurement
      diopter-hours variable (Dh) were done twice, in the period from January 2011
      until January 2012. RESULTS: A multivariate regression analysis of impact on the
      difference of distance visual acuity without correction to the right and left eye
      and difference of automatic computer refractometry in cycloplegia of both eyes
      indicates that, diopter-hours variable (Dh) had statistically significant impact
      on increase of distance visual acuity difference (right eye OR: I measurement-Dh
      1.489, II measurement-Dh 1.544, p<0.05; left eye OR: I measurement-Dh 1.602, II
      measurement-Dh 1.538, p<0.05) and automatic computer refractometry in cycloplegia
      (right eye OR: I measurement 1.361, II measurement 1.493, p<0.05; left eye OR: I
      measurement 0.931, II measurement 1.019, p<0.05) during both measurements.
      CONCLUSION: Near work cause the increase of myopia. This research opened a
      perspective for other researches on the impact of near work on myopia.

PMID- 24944533
TI  - Evolution of Sports-medical Team Management in the Program of Posture Correction
      in Children.
AB  - GOALS: The goal of this study was to determine the effectiveness of the
      organization and coordination of multidisciplinary team consisted of health and
      kinesiology professionals at the correction of posture among girls in the period
      of the second phase of intense growth and development. MATERIAL AND METHODS:
      Testing was conducted on a sample of 70 girls, aged 11.9+/-2.3 years, in which by
      the expert evaluation is recorded weakness of individual muscle groups, but also
      of the whole musculature. For the assessment of posture we applied the method of
      Napoleon Wolanski. Used are 9 variables that included the observed region of the
      body and an overall assessment of posture. The subjects were included in the
      program of kinesiology treatment with duration of 28 weeks. For all the
      parameters have been applied statistical procedures at univariate and
      multivariate level. RESULTS: Data on subjects were obtained by measuring the same
      variables at two time points, i.e. before and after the application of
      kinesiology treatments. Analyses of differences arithmetic mean and mean values
      were done with the t-test for paired samples. In order to determine global
      quantitative differences of tested variables tested discriminant analysis was
      applied. The results showed that the models which complement the experience and
      practical application of expert health professionals and kinesiology knowledge is
      a very effective tool for improving posture of girls in the second phase of
      intensive growth and development. In this way can be prevented health problems
      that might arise later in life.

PMID- 24944534
TI  - Evaluation of patients cooperation in hypertension control.
AB  - INTRODUCTION: Hypertension (high blood pressure) is one of the most widely spread
      diseases of our time and one of the leading risk factors for heart and vascular
      diseases, particularly stroke and coronary heart disease. According to the World
      Health Organization (WHO) cardiovascular diseases are the leading cause of death
      in the world of who dies each year about 17 million persons, of which 5 million
      in Europe. The World Health Organization estimates based on monitoring of
      demographic trends, trends in mortality and morbidity as economic models, further
      growth of cardiovascular diseases, especially in developing countries. GOAL:
      Correlate the success of antihypertensive therapy and provoking factors, and to
      determine the degree of satisfaction with the effect of antihypertensive therapy
      of the patient. MATERIAL AND METHODS: The study was conducted at the Primary
      Health Care Center Stari Grad - Sarajevo. Conducted is study that included 80
      patients. Data for this study were collected by a questionnaire. The
      questionnaire was completed by the examiner using interviews with patients and
      their relatives (parents, guardians).After sorting, control and grouping the data
      were imported into the statistical software package SPSS 20.0, where after
      defining variables was performed statistical analysis. RESULTS: The average age
      of male respondents was 60.80+/-13.03 and 63.50 +/- 7.48 years of female
      respondents. The average value of systolic blood pressure amounted to 148mmHg
      (130-180), while the average value of diastolic blood pressure was 88.75mmHg (70
      120). Student's t test showed that the average value of systolic pressure was
      statistically significantly different from the reference value (t=2.387, DF=19,
      p=0.028), and also the average values of diastolic blood pressure were
      statistically significantly different compared to baseline (p=3.561, DF=19,
      p=0.002). Of the total number of subjects included in this study good blood
      pressure control had 58 participants, and the average value of systolic blood
      pressure was 122mmHg and diastolic 74mmHg. With poor regulation of blood pressure
      were 22 patients, with average values of systolic pressure of 155.5mmHg and
      diastolic 92 mmHg. The most common additional factor influencing the increase in
      blood pressure of patients surveyed was stress is 65 % (n=52), followed by heat
      20% (n=16), and salty foods was a provoking factor in 15% (n=12) subjects. By
      analyzing the frequency of controlling blood pressure has been determined that
      respondents on average control blood pressure once a week, and control frequency
      is in range from daily to monthly. The average value of the blood pressure of
      subjects who regularly used antihypertensive therapy amounted to 125/69 mmHg,
      while the respondents who did not regularly use the antihypertensive therapy that
      value was 157/96 mmHg.

PMID- 24944535
TI  - Effect of combination therapy on cardiovascular risk in the pit miners with
      hypertension, metabolic syndrome and depression.
AB  - BACKGROUND: Higher cardiovascular (CV) morbidity and mortality in depressed
      patient has demonstrated repeatedly. AIM: Determine the degree of occurrence of
      hypertension, metabolic syndrome (MetS) and depression in the pit miners and the
      impact of the six-month holistic treatment of all CV risk factors and depression
      in the overall CV risk in miners with hypertension, MetS and depression. METHODS:
      From 492 pit miners was taken smoking status, measured blood pressure, waist
      circumference and body mass index. Analysis was done using the concentration of
      sugar in blood, triglycerides, total cholesterol, HDL, LDL cholesterol and
      determined total CV risk. All respondents filled self-assessment Beck's
      depression scale. Prevalence MetS hypertension and depression were determined.
      Group of 67 patients with joint hypertension, MetS and depression that is treated
      six months with psychotropic and somatotropin medication, was singled out. After
      six months, the effect of therapy on the risk factors and total CV was assessed.
      RESULTS: Among 492 miners 67 (13,61%) of them had hypertension, MetS and
      depression. After six months treatment, it showed statistically significant
      reduction in blood pressure (p=0,0001), waist circumference (p=0,0001) ,total
      (p=0,002), HDL (p=0,007) and LDL cholesterol (p=0,003), smoking (p=0,002), Beck's
      scale results (p=0,007) and reduction in total CV risk. CONCLUSION: After six
      month of combine therapy in respondents has led to reduced CV risk and level of
      all factors, except BMI and triglycerides.

PMID- 24944536
TI  - Adverse events in affiliated hospitals of mazandaran university of medical
      sciences.
AB  - Due to the complexity of the hospital environment, its structure faces with
      multiple hazards. The risks whether by providing the care and whether by hospital
      environment endanger patients, relatives and care providers. Therefore, a more
      accurate reporting and analysis of the report by focusing on access to
      preventative methods is essential. In this study, hospitals' adverse event that
      has sent by affiliated hospitals of Mazandaran University of Medical Sciences to
      deputy for treatment has studied. 

PMID- 24944537
TI  - Comparison of the effects of mediterranean temperate and cold mountain climates
      on human fertility.
AB  - BACKGROUND: Owing to the emergence of some challenges in the demographic
      structure of many countries and possible decrease in young human workforce in the
      future decades, the reduction in the fertility rate has become a major public
      concern. This study aimed to investigate the effects of climatic factors on
      fertility. AIM: In this correlational study conducted during 2005-2009, the
      relationship between climatic factors (monthly average temperature, air pressure,
      rainfall, and humidity) and monthly fertility in women living in areas with two
      different climates was investigated. METHODS: THE STUDY REGIONS INCLUDED TWO
      CITIES OF IRAN: Behshahr and Hamedan having temperate Mediterranean climate and
      cold mountain climate, respectively. The means and standard deviations of the
      investigated variables were computed and reported. Furthermore, Pearson
      correlation coefficients and linear regression were also employed. RESULTS: The
      findings indicated that monthly fertility in women living in temperate
      Mediterranean climate was related to temperature (r = -0.340, p = 0.008), air
      pressure (r = -0.502, p = 0.002), and rainfall (r = 0.319, p = 0.013), whereas
      this relationship was not found in women living in cold mountain climate.
      Furthermore, fecundity peak was observed during autumn in both the climates.
      CONCLUSIONS: Considering the influences of climatic factors on fertility, it
      would be better if physicians pay attention to other aspects of human fertility
      than the clinical conditions during client evaluation.

PMID- 24944539
TI  - Reforms and Challenges of Post-conflict Kosovo Health System.
AB  - Before its collapse, Kosovo's healthcare system was an integrated part of the
      Former Yugoslav Republics System (known as relatively well advanced for its
      time). Standstill had begun in the last decade of the twentieth century as the
      result of political disintegration of the former state. The enthusiasm of the
      healthcare professionals and the people of Kosovo that at the end of the conflict
      healthcare services will consolidate did not prove just right. Although we can
      claim that reorganization of Kosovo healthcare was a serious push (especially in
      the first years after the conflict), the intensity of development begun to fall
      at the latter stages. Although the basic legislation for the operation of the
      Healthcare System today in Kosovo does exist, the largest cause for the reform
      stagnation is where the law is not implemented properly and measures are not set
      as to a meaningful system of accountability. Twelve years have passed by since
      the 1999 war-conflict and, although, Kosovo has made progress in many other
      spheres, it has not yet reached to consolidate a health system comparable to
      those of other European countries. Intending to get out of difficult situation,
      several healthcare strategic plans have been developed in the past decade in
      Kosovo, but attempts in this direction have not been particularly fruitful. This
      script describes the actual Healthcare complexity of a situation in Kosovo 12
      years after the end of the 1999 war-conflict. Interconnection and historical
      background is also looked upon and is described in the flow of events. Finally,
      the description of transfer competencies from international administrators to the
      local authorities as well as the flow of strategic planning that took place since
      1999 has also been analyzed. 

PMID- 24944538
TI  - Evaluation of thrombocytopenia in systemic lupus erythematosus and correlation
      with different organs damages.
AB  - INTRODUCTION: Thrombocytopenia is highly prevalent among patients with Systemic
      Lupus Erythematous(SLE) and at the same time it has been reported that a
      correlation exists between Thrombocytopenia and organ damage. The aim of this
      study is to highlight the correlation between Thrombocytopenia and the clinical
      manifestations of SLE. OBJECTIVES: The objective is to show the clinical
      manifestations and organ damage of Systemic Lupus Erythematous (SLE) patients who
      have been found to have Thrombocytopenia. METHODS: A retrospective study was
      conducted examining all patient charts diagnosed and treated for SLE at the
      Rheumatology Service of Mother Teresa Hospital Centre. All the data were
      collected from discharged patient charts. The data included were Anti DNA,AAN,C3
      , thrombocytopenia, leucopenia, and organ damage. Data were taken from 2009 to
      2013. The classification criteria of the American College of Rheumatology was
      used for all patients regarding the diagnosis. RESULTS: Out of 330 patients, 12
      (3.64%) are men and 318 (96.3%) women. 73 of all patients have thrombocytopenia
      as cases and 257 patients had SLE without thrombocytopenia, which was considered
      as the control group. AAN 68(93.1%), Anti DNA 50 (64.3%) , low value of C3 46
      (63%), and leucopenia were higher in thrombocytopenic patients compared with
      control group (p<0.05) 48 (65.7%) of thrombocytopenic patients develop lupus
      nephritis, 10 (13.6%) were with pulmonary involvement, and 42 (57.5%) had
      leukopenia. CONCLUSION: Thrombocytopenia is not directly associated with any
      disease activity, organ damage and mortality, but it should be considered as a
      prognostic factor which may help identifying a category of patients whose disease
      course can be aggravated.

PMID- 24944540
TI  - Hepatitis B genotypes in iran.
AB  - Hepatitis B virus (HBV) infection is a public health problem as a cause of liver
      diseases including hepatocellular carcinoma and cirrhosis. It is estimated that
      350 million people live with chronic infection and about one million people die
      every year from complication of this chronic disease in the world. So far, ten
      HBV genotypes (A-J) has been identified which show a geographical distribution.
      Throughout the world, carrier variability rate for hepatitis B infection is
      estimated to be 0.1% to 20%, with regions classified as having low endemicity
      (<2%), intermediate endemicity (2-7%) and high endemicity (>8%). The prevalence
      of hepatitis B infection is estimated at 2 to 7 percent In Iran. After HBV
      vaccination program the prevalence of hepatitis B infection has been reported
      less than 2%, so Iran can be considered one of the countries with low HBV
      infection endemicity. In Iran several studies were shown that the only genotype
      of HBV(100%)was found genotype D as the prominent type in some provinces, but
      some studies reported genotype B(5%)as well as genotype D(95%).The distribution
      of HBV genotypes may guide us in determining disease burden, prognosis and
      antiviral responses. So, it is important to know the epidemiologically of HBV
      genotyping as well. 

PMID- 24944541
TI  - Adverse effects of thalidomide administration, in patients with myeloma
      multiplex?
AB  - INTRODUCTION: Myeloma multiplex is defined by the presence of monoclonal plasma
      cell population in the bone marrow>10%,M protein in the serum and/or urine ,and
      clinical evidence of end organ damage like hypercalcemia ,renal failure, anemia,
      or bone lesions. In the most hematologic malignancies the role of induction
      treatment is to achieve complete remission (CR). Thalidomide became a new
      therapeutic approach but use of Thalidomide as a single agent or combination with
      steroids or chemotherapy is associated with several side effects like deep vein
      thrombosis (DVT), peripheral neuropathy (PN), constipation, somnolence, pyrexia,
      pain, fatigue osteonecrosis of jaw, and teratogenicity that is the most worrying
      adverse event. Risk of appearance of DVT increased if we use combination of
      Thalidomide plus Dexamethasone plus cytotoxic chemotherapy such Cyclophosphamide.
      >30% DVT usually occurs during the first months of treatment and is more frequent
      in newly diagnosed patients with a high tumor burden. The second side effect is
      peripheral neuropathy (PN) which occurs in 50% of patients with MM treated with
      Thalidomide plus Dexamethasone and chemotherapy. PATIENTS AND METHODS: Eighty
      patients of both sexes (43 males and 37 females) at the age of 31-81 (median
      range 58 years) with MM, were treated-one group with combinations of Thalidomide
      plus Dexamethasone plus Cyclophosphamide (CyThalDex) 4 cycle(>4months), and the
      other group with Thalidomide plus Dexamethasone plus Melphalan (MPT), (>4month)
      and third group with high dose of chemotherapy and continue with ThalDex (TD),
      the fourth group with CyThalDex, > than 5 cycles, and the fifth group with
      ThalDex (TD) only. RESULTS: It is obvious while myelo-suppression is very rare,
      the incidence of nonhematologic side effects is high and dose dependent. Eight
      (or 10%) patients that developed DVT and CVI were initially treated with
      antiaggregation therapy of Aspirin 100mg per day, but those that already
      developed were treated with low dose of Heparin 40000 iE per day in ten days and
      continued with oral anticoagulans therapy. However, besides the given therapy in
      four (or 5 %) patients there was exitus letalis. PN was developed in twentyone
      patients (or 26.25%) from the total number of patients treated with Thalidomide,
      in ten patients the dosage of Thalidomide was decreased to 50mg per day, in one
      patient with Epi attacks it was interrupted and the other was with paresis
      n.occulomotorius and n.abducens. CONCLUSIONS: Patients treated with thalidomide
      have an increased risk of arterial thromboembolism, including myocardial
      infarction and cerebrovascular events, in addition to the established risk of
      venous thromboembolism, but most patients who presenting DVT or some of
      thromboembolic events have had identifiable risk factors. The prolonged exposure
      to Thalidomide seems to induce resistance of MM reducing overall survival (OS).
      We must evaluate consolidation and maintenance therapies with Thalidomide,
      determinate which regimens provide a highness benefit with favorable side effect
      profiles in specific subgroups of patients.

PMID- 24944542
TI  - Public awareness on cancerous substances.
AB  - The public can be defined as a mosaic consisting of various ethnic, religious and
      other social groups, hence the definition of public includes each individual
      persona. Public opinion is the voice of such public and is, therefore, considered
      a worthy element in political and economic discourse. Media can do much in
      providing education necessary for informing the public about cancerous substances
      in the environment. The purpose of this study is to inform the public about
      issues that truly matter instead of following the current trend and focus on the
      topics and issues of less importance. 

PMID- 24944543
TI  - Plagiarism in scientific research and publications and how to prevent it.
AB  - Quality is assessed on the basis of adequate evidence, while best results of the
      research are accomplished through scientific knowledge. Information contained in
      a scientific work must always be based on scientific evidence. Guidelines for
      genuine scientific research should be designed based on real results. Dynamic
      research and use correct methods of scientific work must originate from everyday
      practice and the fundamentals of the research. The original work should have the
      proper data sources with clearly defined research goals, methods of operation
      which are acceptable for questions included in the study. When selecting the
      methods it is necessary to obtain the consent of the patients/respondents to
      provide data for execution of the project or so called informed consent. Only by
      the own efforts can be reached true results, from which can be drawn conclusions
      and which finally can give a valid scholarly commentary. Text may be copied from
      other sources, either in whole or in part and marked as a result of the other
      studies. For high-quality scientific work necessary are expertise and relevant
      scientific literature, mostly taken from publications that are stored in
      biomedical databases. These are scientific, professional and review articles,
      case reports of disease in physician practices, but the knowledge can also be
      acquired on scientific and expert lectures by renowned scientists. Form of text
      publications must meet standards on writing a paper. If the article has already
      been published in a scientific journal, the same article cannot be published in
      any other journal with a few minor adjustments, or without specifying the parts
      of the first article which is used in another article. Copyright infringement
      occurs when the author of a new article, with or without mentioning the author,
      uses a substantial portion of previously published articles, including past
      contributions in the first article. With the permission of the publisher and the
      author, another journal can re-publish the article already published. In that
      case, that is not plagiarism, because the journal states that the article was re
      published with the permission of the journal in which the article is primarily
      released. The original can be only one, and the copy is a copy, and plagiarism is
      stolen copy. The aim of combating plagiarism is to improve the quality, to
      achieve satisfactory results and to compare the results of their own research,
      rather than copying the data from the results of other people's research. Copy
      leads to incorrect results. Nowadays the problem of plagiarism has become huge,
      or widespread and present in almost all spheres of human activity, particularly
      in science. Scientific institutions and universities should have a center for
      surveillance, security, promotion and development of quality research.
      Establishment of rules and respect the rules of good practice are the obligations
      of each research institutions, universities and every individual researchers,
      regardless of which area of science is being investigated. There are
      misunderstandings and doubts about the criteria and standards for when and how to
      declare someone a plagiarist. European and World Association of Science Editors
      (EASE and WAME), and COPE - Committee on Publishing Ethics working on the precise
      definition of that institution or that the scientific committee may sanction when
      someone is proven plagiarism and familiarize the authors with the types of
      sanctions. The practice is to inform the editors about discovered plagiarism and
      articles are withdrawn from the database, while the authors are put on the so
      called black list. So far this is the only way of preventing plagiarism, because
      there are no other sanctions. 

PMID- 24944544
TI  - Brain Electrical Activity of Shy and Non-Shy Preschool-Aged Children during
      Executive Function Tasks.
AB  - Psychophysiological and cognitive performance differences exist between shy and
      non-shy individuals. Neuroimaging studies have shown identifiable differences in
      task-related cortical functioning between adults with and without sensitivity to
      social events. The current study compared baseline and task measures of EEG power
      (6-9 Hz) for 125 shy and non-shy children between the ages of 41-55 months who
      differed in core executive function (EF) skills. Results indicated an increase in
      medial frontal EEG power from baseline-to-task for high EF performers (shy and
      non-shy). Shy/low EF performers also demonstrated this increase, but the non
      shy/low EF group did not. For the medial parietal region, only the shy children
      (high and low EF performers) showed an increase in power from baseline-to-task;
      and for the shy/high EF group, left hemisphere power was greater than the right
      during baseline and task. This study is believed to be the first continuous
      recording EEG comparison between children who are shy and non-shy in the context
      of an EF assessment. These findings highlight differences in medial frontal and
      medial parietal power for children who differ in shyness and EF skills. They also
      suggest the value of future research examining strong EF skills as protective and
      regulatory for shy children.

PMID- 24944547
TI  - A SPECIAL MEETING REVIEW EDITION: Updates in the Treatment of Hepatitis C Virus
      Infection From EASL 2012: The 47th Annual Meeting of the European Association for
      the Study of the LiverApril 18-22, 2012 * Barcelona, SpainSpecial Reporting on:*
      Safety of Telaprevir or Boceprevir in Combination with Peginterferon
      alpha/Ribavirin in Cirrhotic Nonresponders. First Results of the French Early
      Access Program (ANRS C020-CUPIC)* SVR in Prior Peginterferon/Ribavirin (PR)
      Treatment Failures After Re-treatment with Boceprevir + PR: The PROVIDE Study
      Interim Results* Futility Rules in Telaprevir Combination Treatment* Boceprevir
      Plus Peginterferon/Ribavirin for the Treatment of HCV/HIV Co-Infected Patients:
      End-of-Treatment (Week 48) Interim ResultsPLUS Meeting Abstract Summaries With
      Expert Commentary by: Jean-Pierre Bronowicki, MD, PhDDepartment of Hepato
      GastroenterologieCentre Hospitalier Universitaire de Nancy-BraboisVandoeuvre-les
      Nancy, France.

PMID- 24944545
TI  - Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with
      joint damage, assessed eight years after onset of juvenile idiopathic arthritis
      (JIA).
AB  - BACKGROUND: Early appearance of antibodies specific for native human type II
      collagen (anti-CII) characterizes an early inflammatory and destructive phenotype
      in adults with rheumatoid arthritis (RA). The objective of this study was to
      investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum
      samples obtained early after diagnosis, and to relate the occurrence of
      autoantibodies to outcome after eight years of disease in children with juvenile
      idiopathic arthritis (JIA). METHODS: The Nordic JIA database prospectively
      included JIA patients followed for eight years with data on remission and joint
      damage. From this database, serum samples collected from 192 patients, at a
      median of four months after disease onset, were analysed for IgG anti-CII, IgM
      RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile
      Arthritis Damage Index for Articular damage (JADI-A), a validated clinical
      instrument for joint damage. RESULTS: Elevated serum levels of anti-CII occurred
      in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients.
      Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti
      CII. The polyarticular and oligoarticular extended categories were
      overrepresented in patients with two or more autoantibodies. Anti-CII occurred in
      younger children, usually without overlap with the other autoantibodies and was
      associated with high levels of C-reactive protein (CRP) early in the disease
      course. All four autoantibodies were significantly associated with joint damage,
      but not with active disease at the eight-year follow up. CONCLUSIONS: Anti-CII,
      anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint
      damage when assessed after eight years of disease. The role of anti-CII in JIA
      should be further studied.

PMID- 24944548
TI  - A SPECIAL MEETING REVIEW EDITION: Highlights in Anti-Tumor Necrosis Factor
      Monitoring: Digestive Disease Week 2012May 19-22, 2012 * San Diego,
      CaliforniaSpecial Reporting on:* Novel Infliximab and Antibody-to-lnfliximab
      Assays Are Predictive of Disease Activity in Patients with Crohn's Disease*
      Antibodies to Infliximab Can Either Be Persistent or Transient: A Retrospective
      Case-Control Study in IBD Patients Treated with Infliximab Maintenance Therapy*
      Putting It Together: Drug Levels and Disease Activity to Tailor Therapy*
      Infliximab Concentration and Clinical Outcome in Patients with Ulcerative
      ColitisPLUS Meeting Abstract Summaries With Expert Commentary by: William J.
      Sandborn, MDChief of the Division of GastroenterologyDirector of the UCSD IBD
      CenterUC San Diego Health SystemLa Jolla, California.

PMID- 24944546
TI  - Acute versus chronic supplementation of sodium citrate on 200 m performance in
      adolescent swimmers.
AB  - BACKGROUND: A double-blinded, placebo-controlled, cross-over design was used to
      investigate whether two different sodium citrate dihydrate (Na-CIT)
      supplementation protocols improve 200 m swimming performance in adolescent
      swimmers. METHODS: Ten, male swimmers (14.9 +/- 0.4 years of age; 63.5 +/- 4 kg)
      performed four 200 m time trials with the following treatments: acute (ACU)
      supplementation (0.5 g kg(-1) administered 120 min pre-trial), acute placebo (PLC
      A), chronic (CHR) supplementation (0.1 g?kg(-1) for three days and 0.3 g kg(-1)
      on the forth day 120 min pre-trial), and chronic placebo (PLC-C). The order of
      the trials was randomized, with at least a six-day wash-out period between
      trials. Blood samples were collected by finger prick pre-ingestion, 100 min post
      ingestion, and 3 min post-trial. Performance time, rate of perceived exertion,
      pH, base excess, bicarbonate and lactate concentration were measured. RESULTS:
      Post-ingestion bicarbonate and base excess were higher (P < 0.05) in both the ACU
      and CHR trials compared to placebo showing adequate pre-exercise alkalosis.
      However, performance time, rate of perceived exertion as well as post-trial pH
      and lactate concentration were not significantly different between trials.
      Further analysis revealed that five swimmers, identified as responders, improved
      their performance time by 1.03% (P < 0.05) and attained higher post-trial lactate
      concentrations in the ACU versus PLC-A trial (P < 0.05). They also had
      significantly higher post-trial lactate concentrations compared to the non
      responders in the ACU and CHR trials. CONCLUSIONS: Acute supplementation of Na
      CIT prior to 200 m swimming performance led to a modest time improvement and
      higher blood lactate concentrations in only half of the swimmers while the
      chronic Na-CIT supplementation did not provide any ergogenic effect in this group
      of adolescent swimmers. TRIAL REGISTRATION: Clinicaltrials.gov NCT01835912.

PMID- 24944549
TI  - Modern therapeutic concepts of early breast cancer.

PMID- 24944551
TI  - Late recurrences in early breast cancer: for whom and how long is endocrine
      therapy beneficial?
AB  - During the last decade, besides the well-established clinical-pathological
      predictors for the risk of late recurrence in breast cancer, such as estrogen
      receptor status, and T and N stage, a variety of multigene assays have been shown
      to improve prognostication and prediction in this setting. Several clinical
      trials have evaluated the role of extended endocrine therapy with tamoxifen
      (ATLAS) or aromatase inhibitors (MA.17, NSABP-B33 and ABCSG 6a), and other
      randomized studies are still ongoing. However, among this patient population, it
      is still not clear who could benefit from extended therapy and what the optimal
      treatment duration should be. New multigene assays such as EndoPredict, PAM50 ROR
      score, HOXB13/IL17BR ratio and Breast Cancer Index provide significant and
      relevant prognostic information concerning the likelihood of recurrence beyond 5
      years after surgery. The identified low-risk subgroups not only show a very
      favorable prognosis, they also seem to have only little benefit from extended
      aromatase inhibitor therapy. Many of these reverse transcriptase/polymerase chain
      reaction-based techniques have been validated in archived tumor material from
      large phase III trials, and will soon be available to routine pathology
      laboratories as an aid in clinical decision-making for patients. 

PMID- 24944550
TI  - Local treatment of the axilla in early breast cancer: concepts from the national
      surgical adjuvant breast and bowel project B-04 to the planned intergroup
      sentinel mamma trial.
AB  - Local treatment of the axilla in clinically node-negative, early-stage breast
      cancer patients has been hotly debated after the release of the American College
      of Surgeons Oncology Group (ACOSOG) Z0011 findings. However, this review does not
      focus on the 'Z0011-eligible' patients alone, because this subgroup represents a
      minority of our patients undergoing breast-conserving surgery (BCS) and sentinel
      lymph node biopsy (SLNB). The following topics are discussed: axillary
      diagnostics, timing of axillary procedures in the neoadjuvant setting, long-term
      follow-up of SLNB trials, omission of axillary surgery in randomized trials,
      management of the involved axilla with low tumor volume, positive sentinel lymph
      nodes and BCS, involved sentinel lymph nodes and mastectomy, and axillary
      radiotherapy. Finally, the current innovative study concepts (i.e. Sentinel Node
      versus Observation after Axillary Ultrasound (SOUND) and Intergroup Sentinel
      Mamma (INSEMA)) including patients with axillary observation alone in clinically
      node-negative women are presented. 

PMID- 24944552
TI  - Intraoperative Electron Radiotherapy (IOERT) as an Alternative to Standard Whole
      Breast Irradiation: Only for Low-Risk Subgroups?
AB  - BACKGROUND: Intraoperative radiotherapy during breast-conserving surgery is being
      studied as an alternative to 6 weeks of external beam radiotherapy (EBRT) for low
      risk women; it can be delivered using electrons (intraoperative electron
      radiotherapy, IOERT) or 50-kV X-rays. MATERIALS AND METHODS: We analyzed both
      single institutional and randomized studies involving single-fraction IOERT
      treatments. Rates for ipsilateral breast tumor recurrences, disease-specific
      survival, and overall survival were obtained. RESULTS: IOERT had true 5-year
      recurrence rates of > 1.5% for ASTRO (American Society for Radiation Oncology)
      and ESTRO (European Society for Therapeutic Radiology and Oncology) suitable
      women, or for low-risk women as defined by the ELIOT trial. Women with ductal
      carcinoma in situ eligible for breast-conserving therapy, older women that
      currently receive no EBRT, and younger women with favorable biology are
      additional potential candidates. CONCLUSION: ASTRO suitable and ESTRO good women
      for accelerated partial breast irradiation are low-risk groups. Higher-risk women
      with favorable biology might also be suitable candidates for IOERT, providing the
      tumor biology can be determined prior to surgery. For intraoperative radiotherapy
      using 50-kV X-rays, follow-up was too short to assess the effectiveness of the
      treatment.

PMID- 24944553
TI  - Accuracy of prognostic and predictive markers in core needle breast biopsies
      compared with excisional specimens.
AB  - BACKGROUND: Core needle biopsy (CNB) is widely accepted for preoperative
      diagnosis of breast cancer and sometimes can be the only way of providing a
      suitable specimen for prognostic and predictive marker studies prior to
      neoadjuvant treatment. The purpose of this study was to evaluate the accuracy of
      CNB by comparing histological tumor type and grade as well as estrogen receptor
      (ER), progesterone receptor (PR), p53, and HER2/ neu status by
      immunohistochemistry in CNB and excisional surgical specimens. PATIENTS AND
      METHODS: During a 2.5-year study period, we identified 30 patients with breast
      cancer, who underwent CNB and definitive surgery. To evaluate the accuracy of
      CNB, tumor grade, ER, PR, HER2, and p53 status were immunohistochemically
      determined in both the CNB and the surgical specimens, and concordance of results
      between the 2 specimens was assessed. RESULTS: The concordance rate was 100% for
      histological type, 66.6% for histological grade, and 96.7, 90, 76.7 and 93.3% for
      ER, PR, p53 and HER2/neu, respectively. CONCLUSION: Our study showed that CNB has
      an excellent accuracy for tumor type, ER, and HER2/ neu; however, it should be
      used cautiously for tumor grade, PR, and p53 status. Thus, excisional biopsy is
      recommended for the determination of these factors.

PMID- 24944554
TI  - Idiopathic Granulomatous Mastitis: Comparison of Wide Local Excision with or
      without Corticosteroid Therapy.
AB  - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is an uncommon chronic
      inflammatory disease of the breast with uncertain optimal treatment regimen. In
      this study, our purpose was to report our clinical experience with 74 IGM
      patients who were treated wide local excision with or without steroid therapy.
      PATIENTS AND METHOD: 74 cases diagnosed histologically as IGM were identified
      from surgical and pathological records between January 1995 and January 2012.
      Group 1 (surgery-only group) comprised 53 patients, and the 21 patients in group
      2 were treated with corticosteroids prior to surgical treatment (steroid-and
      surgery group). RESULTS: Follow-up data were complete for 67 (91.7%) of the 73
      patients. Recurrence developed in 4 (7.5%) patients in the surgery-only group,
      while there was no recurrence in the steroid-and-surgery group; the difference
      was not statistically significant (p = 0.19). CONCLUSION: Systemic steroid
      therapy with surgical resection is the recommended first-line treatment strategy
      for IGM.

PMID- 24944556
TI  - Important Factors Affecting Adjuvant Treatment Decision in Stage IA Breast Cancer
      Patients in Turkey.
AB  - INTRODUCTION: In Turkey, the gene expression profile test is not standard, so
      adjuvant treatment is planned according to clinicopathological factors.
      Therefore, we retrospectively analyzed important parameters that affect the
      decision on adjuvant chemotherapy, and also factors related to survival in stage
      IA breast cancer patients in Turkey. METHODS: We retrospectively evaluated 347
      stage IA patients. The relationship between the clinicopathological parameters
      and adjuvant chemotherapy was analyzed. RESULTS: The median age and follow-up
      time were 52 years (range: 25-86) and 22.6 months (range: 1-113), respectively.
      The 5-year disease-free survival (DFS) and overall survival (OS) rates were 87.9%
      and 98.7%, respectively, but the median DFS was not reached. Age, estrogen
      receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and
      the presence of triple-negative breast tumor (TNBC) were related to DFS, and
      lymphovascular invasion (LVI), perineural invasion (PNI), HER2 status, the
      presence of TNBC, and recurrence were related to OS (p > 0.05). Furthermore, age,
      menopausal status, multicentricity, grade, tumor size, necrosis, ER, the presence
      of TNBC, and HER2 were found to be related to adjuvant therapy decision (p >
      0.05). All these parameters, in addition to LVI and PNI, were independent factors
      for chemotherapy by logistic regression analysis. CONCLUSIONS: In decisions about
      adjuvant therapy in stage IA breast cancer patients, clinicopathological factors
      should be kept in mind.

PMID- 24944555
TI  - Should a drain be placed in early breast cancer surgery?
AB  - BACKGROUND: The current surgical debate has led to a reduction in the extent of
      surgery performed and thereby to a reduced occurrence of surgical trauma and,
      over the recent years, reduced seroma formation. This reduction in surgical
      procedures calls the need for a drain into question. METHOD: Using Google Scholar
      and the National Library of Medicine (PubMed), a literature review was performed
      on systematic reviews and meta-analyses regarding breast cancer surgery +/-
      axillary dissection. Additionally, randomized trials for the time period after
      the last systematic review were included and evaluated according to the Jadad
      score. RESULTS: The search returned 5 systematic reviews, in which a total of
      1,075 patients were included (537 cases and 538 controls). Since the last review,
      no prospective randomized trial meeting the inclusion criteria has been
      published. The current reviews conclude that insertion of a drain is associated
      with a longer hospital stay and reduced seroma formation. The data regarding
      wound infection and drain insertion is inconclusive. The omission of a drain is
      associated with early discharge, reduced postsurgical pain, and early
      mobilization, but also with an increase in outpatient seroma aspirations.
      CONCLUSION: The omission of a drain is possible in early breast cancer surgery
      (wide local excision and sentinel node biopsy) with adequate surgical techniques
      and instruments.

PMID- 24944557
TI  - Brief Distress Screening in Clinical Practice: Does it Help to Effectively
      Allocate Psycho-Oncological Support to Female Cancer Inpatients?
AB  - BACKGROUND: The usefulness of distress screening in cancer inpatient settings has
      rarely been investigated. This study evaluated a brief distress screening of
      inpatients in a breast cancer centre and a gynaecological cancer centre. PATIENTS
      AND METHODS: Hospitalised patients with breast or gynaecological cancers were
      screened with the Distress Thermometer. Patients who scored above the cut-off,
      were referred by the medical staff, or self-referred were offered bedside psycho
      oncological counselling. RESULTS: Of 125 patients, 68 (54.4%) received an offer
      of counselling, and 62 patients (49.6%) accepted. Most of the counselling was
      induced by distress screening. Only 4 (3.2%) patients self-referred to the
      counselling service. Of the counselled patients, 65.8% stated that they had
      substantially benefited from psycho-oncological support; only 5.6% of the non
      counselled patients indicated that they might have benefited from psycho
      oncological support. CONCLUSION: Almost all patients who will accept and benefit
      from psycho-oncological counselling can be identified if distress screening is
      used in conjunction with referrals by physicians and nurses. Distress screening
      is a worthwhile component in a framework of psycho-oncological support in a
      cancer inpatient setting. It paves the way to counselling for cancer inpatients
      who need it and are willing to accept it but hesitate to self-refer to psycho
      oncological services.

PMID- 24944558
TI  - Alleviation of brain edema and restoration of functional independence by
      bevacizumab in brain-metastatic breast cancer: a case report.
AB  - BACKGROUND: Brain metastases (BM) are an increasing challenge in modern oncology,
      as treatment options especially after exhaustion of local treatment approaches
      are very limited. PATIENT AND METHODS: A long-term surviving patient with brain
      only metastatic breast cancer, who presented at our department with massive
      corticosteroid-refractory brain edema with serious neurological symptoms after
      exhaustion of all local therapy options, was started on bevacizumab. RESULTS:
      Initiation of bevacizumab monotherapy led to rapid decrease of contrast-enhancing
      lesions and alleviation of brain edema, and allowed tapering and termination of
      corticosteroid administration. Neurological and neurocognitive function was
      restored and marked improvement in quality of life was observed. CONCLUSION: Our
      case highlights that bevacizumab may represent a feasible and effective salvage
      treatment option in selected patients with BM.

PMID- 24944559
TI  - Optimal Sequencing of Anti-HER2 Therapy.

PMID- 24944560
TI  - Pyrosequencing Evaluation of Widely Available Bisulfite Conversion Methods:
      Considerations for Application.
AB  - INTRODUCTION: Bisulfite treatment of DNA introduces methylation-dependent
      sequence changes through selective chemical conversion of nonmethylated cytosine
      to uracil and serves as pretreatment step for the majority of DNA methylation
      analysis methods. METHODS: We have evaluated the conversion performance of five
      of the most commonly used bisulfite treatment kits [MethylDetector (Active
      Motif), Epitect+ (Qiagen), Zymo Methylation, Zymo Gold and Zymo Lightning (all
      from Zymo Research)] by pyrosequencing four different regions with variable
      methylation levels, including: a repetitive element (ALUSX), a gene with low
      levels of methylation (IL6ST), an imprinted gene expected to be approximately 50%
      methylated (IGF2), and a fully methylated gene (ST3GAL2). In addition, we have
      studied the influence of duration (3 vs. 16 h) and type (fixed temperature vs.
      cycling program) of incubation protocol on the conversion efficiency of each
      evaluated kit. RESULTS: All kits produced similar conversion rates of ALUSX, IGF2
      and ST3GAL2, while the conversion of the low methylated IL6ST gene was variable
      between kits. The Zymo kits were highly consistent in their performance even when
      different protocols of incubation were applied, generating full conversion at the
      low methylated gene IL6; this was not true for the MethylDetector and Epitect+
      kits. However, long-cycling incubation could produce similar conversion rates for
      the same locus in combination with Active Motif and Qiagen kits. CONCLUSIONS: The
      selection of a long-cycling protocol during conversion permits standardization of
      protocols, improving the reproducibility of methylation estimates across
      laboratories for gene-specific, genome-wide and bisulfite-based sequencing
      analyses.

PMID- 24944561
TI  - Reasons for prescribing second generation antihistamines to treat allergic
      rhinitis in real-life conditions and patient response.
AB  - BACKGROUND: Second generation H1 antihistamines (H1A) are currently recommended
      as first choice medications for allergic rhinitis and rhinoconjunctivitis.
      However, little is known about what influences the choice of prescription of one
      second generation (H1A) as opposed to another in real-life conditions. OBJECTIVE:
      The aim of the study was to identify the main criteria determining the choice of
      a second generation H1A by allergy specialists in mainland France. METHODS:
      Consecutive patients suffering from allergic rhinitis or rhinoconjunctivitis were
      included and followed prospectively for 30 days from the prescription of a second
      generation H1A in monotherapy. Patients were asked to fill in auto-questionnaires
      at baseline, daily during the first 10 days of the new treatment, and at the end
      of follow-up. Data on efficacy, tolerance, safety, rate and type of response to
      treatment, as well as patient satisfaction were recorded and analyzed. RESULTS:
      1,080 patients were included between March 2011 and October 2012, mostly
      suffering from moderate to severe rhinitis (82.0%). The most frequently cited
      reason for choosing a specific H1A was the expected efficacy (85.3%). The mean
      time to nasal and ocular recovery was 6 days and 78.2% of patients responded to
      treatment within this interval. The presence of conjunctivitis was significantly
      associated with a more rapid response. At the end of follow-up, the satisfaction
      rate was higher for patients who were switched from a previous treatment (87.5%),
      compared to those receiving their first treatment (78.8%). CONCLUSION AND
      CLINICAL RELEVANCE: The main reason for choosing a specific second generation H1A
      was its expected efficacy. Concomitant conjunctivitis is associated with a more
      rapid response to treatment. Symptom recovery necessitates a mean of 6 days.

PMID- 24944562
TI  - Diagnoses, prevalence, and state-based federal spending for HIV prevention and
      treatment in the United States, 2006-2009.
AB  - BACKGROUND: In response to an article published in 2012 by officials at the US
      Department of Health and Human Services (DHHS), an independent analysis of state
      based federal resource allocation for HIV was conducted to determine if the
      funding accurately reflected diagnosis and prevalence rates. METHODS: Total state
      based federal funding for HIV, state-based funding for HIV prevention, and state
      based funding for HIV treatment were compared to state-based HIV diagnosis and
      prevalence rates from 2006-2009. RESULTS: Total state-based federal funding for
      HIV and funding for HIV prevention and treatment were highly correlated with HIV
      diagnosis and prevalence rates during the time horizon of the study; however,
      correlations between state-based HIV prevention funding and state-based HIV
      diagnosis rates were lower than the correlations between state-based HIV
      treatment funding and HIV prevalence. CONCLUSIONS: Our findings suggest that
      state-based federal resource allocation for HIV prevention and treatment may be
      better aligned with HIV diagnosis and prevalence rates than previously reported;
      however resource allocation for HIV prevention is less aligned than funding for
      HIV treatment signaling the need to reexamine state-based federal funding for HIV
      prevention.

PMID- 24944564
TI  - The impact of services that offer individualised funds, shared management, person
      centred relationships, and self-direction on the lived experiences of consumers
      with mental illness.
AB  - BACKGROUND: Mental health service providers across Australia, including Western
      Australia (WA), have begun to offer individualised funds, shared management,
      person-centred and self-directed (SPS) services. No research exists on the impact
      of SPS services on the lived experiences of these particular consumers. This
      study explored the impact of a SPS service offered for the first time in WA to
      consumers with mental illness. METHODS: Data on sixteen consumers' lived
      experiences were analysed using an abbreviated grounded theory approach. These
      data had been developed by the consumers, Guides (staff) and an independent
      evaluator, and most of it had been collected in the past prior to the
      commencement of the study. RESULTS: Three over-arching categories, and related
      subcategories, emerged indicating that 1) access to individualised funds enabled
      practical and psychological benefits to consumers; 2) consistent contact in
      shared management and person-centred relationships enhanced the provision of
      timely and meaningful staff support to consumers; and 3) high quality shared
      management and person-centred relationships with staff and the opportunity to
      self-direct enabled consumers' change and growth. CONCLUSIONS: SPS services
      enhanced consumers' lived experiences and enabled staff to provide and consumers
      to experience timely access to recovery resources, consistent contact, responsive
      and high quality support, and self-direction of services. In this, consumers
      changed, grew and achieved desired recovery experiences. The overall impact of
      the SPS service seemed to be founded on the goodness of fit between person
      characteristics of staff and consumers, which enabled rich support that provided
      for corrective emotional experiences. This enabled consumers to build meaningful
      and hopeful lives where they started to live with, and beyond, their mental
      illness.

PMID- 24944565
TI  - Research highlights for issue 5: the role of the microbiome in shaping evolution.

PMID- 24944566
TI  - Does recognized genetic management in supportive breeding prevent genetic changes
      in life-history traits?
AB  - Supportive breeding is one of the last resort conservation strategies to avoid
      species extinction. Management of captive populations is challenging because
      several harmful genetic processes need to be avoided. Several recommendations
      have been proposed to limit these deleterious effects, but empirical assessments
      of these strategies remain scarce. We investigated the outcome of a genetic
      management in a supportive breeding for the Houbara Bustard. At the phenotypic
      level, we found an increase over generations in the mean values of gamete
      production, body mass and courtship display rate. Using an animal model, we found
      that phenotypic changes reflected genetic changes as evidenced by an increase in
      breeding values for all traits. These changes resulted from selection acting on
      gamete production and to a lesser extent on courtship display. Selection
      decreased over years for female gametes, emphasizing the effort of managers to
      increase the contribution of poor breeders to offspring recruited in the captive
      breeding. Our results shed light on very fast genetic changes in an exemplary
      captive programme that follows worldwide used recommendations and emphasizes the
      need of more empirical evidence of the effects of genetic guidelines on the
      prevention of genetic changes in supportive breeding. 

PMID- 24944567
TI  - Evidence that hepatitis C virus genome partly controls infection outcome.
AB  - Infection by hepatitis C virus (HCV) leads to one of two outcomes; either the
      infection resolves within approximately 6 months or the virus can persist
      indefinitely. Host genetics are known to affect the likelihood of clearance or
      persistence. By contrast, the importance of the virus genotype in determining
      infection outcome is unknown, as quantifying this effect traditionally requires
      well-characterized transmission networks, which are rare. Extending phylogenetic
      approaches previously developed to estimate the virus control over set-point
      viral load in HIV-1 infections, we simulate inheritance of a binary trait along a
      phylogenetic tree, use this data to quantify how infection outcomes cluster and
      ascertain the effect of virus genotype on these. We apply our method to the
      Hepatitis C Incidence and Transmission Study in prisons (HITS-p) data set from
      Australia, as this cohort prospectively identified incident cases including
      viraemic subjects who ultimately clear the virus, thus providing us with a unique
      collection of sequences from clearing infections. We detect significant
      correlations between infection outcome and virus distance in the phylogeny for
      viruses of Genotype 1, with estimates lying at around 67%. No statistically
      significant estimates were obtained for viruses of Genotype 3a. 

PMID- 24944563
TI  - Nanostructured substrates for isolation of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) originate from the primary tumor mass and enter
      into the peripheral bloodstream. CTCs hold the key to understanding the biology
      of metastasis and also play a vital role in cancer diagnosis, prognosis, disease
      monitoring, and personalized therapy. However, CTCs are rare in blood and hard to
      isolate. Additionally, the viability of CTCs can easily be compromised under high
      shear stress while releasing them from a surface. The heterogeneity of CTCs in
      biomarker expression makes their isolation quite challenging; the isolation
      efficiency and specificity of current approaches need to be improved.
      Nanostructured substrates have emerged as a promising biosensing platform since
      they provide better isolation sensitivity at the cost of specificity for CTC
      isolation. This review discusses major challenges faced by CTC isolation
      techniques and focuses on nanostructured substrates as a platform for CTC
      isolation.

PMID- 24944569
TI  - Population differentiation of zander (Sander lucioperca) across native and newly
      colonized ranges suggests increasing admixture in the course of an invasion.
AB  - In addition to ecological factors, evolutionary processes can determine the
      invasion success of a species. In particular, genetic admixture has the potential
      to induce rapid evolutionary change, which can result from natural or human
      assisted secondary contact between differentiated populations. We studied the
      recent range expansion of zander in Germany focusing on the interplay between
      invasion and genetic admixture. Historically, the rivers Elbe and Danube
      harboured the most north-western source populations from which a north-westward
      range expansion occurred. This was initiated by introducing zander outside its
      native range into rivers and lakes, and was fostered by migration through
      artificial canals and stocking from various sources. We analysed zander
      populations of the native and invaded ranges using nuclear and mitochondrial
      genetic markers. Three genetic lineages were identified, which were traced to
      ancestral ranges. Increased genetic diversity and admixture in the invaded region
      highlighted asymmetric gene flow towards this area. We suppose that the adaptive
      potential of the invading populations was promoted by genetic admixture, whereas
      competitive exclusion in the native areas provided a buffer against introgression
      by novel genotypes. These explanations would be in line with evidence that
      hybridization can drive evolutionary change under conditions when new niches can
      be exploited. 

PMID- 24944568
TI  - Ivermectin sensitivity is an ancient trait affecting all ecdysozoa but shows
      phylogenetic clustering among sepsid flies.
AB  - Avermectins are potent and popular veterinary pharmaceuticals used globally to
      fight parasites of livestock and humans. By disturbing ion channel transport
      through the membrane, avermectins are effective against endo- and ectoparasitic
      round and horsehair worms (Nematoida), insects, or ticks (Arthropoda), but not
      against Plathelminthes, including flatworms (Trematoda) and tapeworms (Cestoda),
      or segmented worms (Annelida). Unfortunately, excreted avermectins have strong
      nontarget effects on beneficial arthropods such as the insect community
      decomposing livestock dung, ultimately impeding this important ecosystem function
      to the extent that regulators mandate standardized eco-toxicological tests of
      dung organisms worldwide. We show that the ancient phylogenetic pattern and
      qualitative mechanism of avermectin sensitivity is conserved and compatible with
      most recent phylogenomic hypotheses grouping the Nematoida with the Arthropoda as
      Ecdysozoa (molting animals). At the species level, we demonstrate phylogenetic
      clustering in ivermectin sensitivities of 23 species of sepsid dung flies
      (Diptera: Sepsidae). This clustered 500-fold quantitative variation in
      sensitivity may indicate recent lineage-specific responses to selection, but more
      likely reflects pre-existing genetic variation with pleiotropic effects on eco
      toxicological responses to pollutants. Regardless, our results question the
      common practice in eco-toxicology of choosing single test species to infer
      detrimental effects on entire species communities, which should ideally assess a
      representative taxonomic sample. 

PMID- 24944570
TI  - Identifying geographic hot spots of reassortment in a multipartite plant virus.
AB  - Reassortment between different species or strains plays a key role in the
      evolution of multipartite plant viruses and can have important epidemiological
      implications. Identifying geographic locations where reassortant lineages are
      most likely to emerge could be a valuable strategy for informing disease
      management and surveillance efforts. We developed a predictive framework to
      identify potential geographic hot spots of reassortment based upon spatially
      explicit analyses of genome constellation diversity. To demonstrate the utility
      of this approach, we examined spatial variation in the potential for reassortment
      among Cardamom bushy dwarf virus (CBDV; Nanoviridae, Babuvirus) isolates in
      Northeast India. Using sequence data corresponding to six discrete genome
      components for 163 CBDV isolates, a quantitative measure of genome constellation
      diversity was obtained for locations across the sampling region. Two key areas
      were identified where viruses with highly distinct genome constellations
      cocirculate, and these locations were designated as possible geographic hot spots
      of reassortment, where novel reassortant lineages could emerge. Our study
      demonstrates that the potential for reassortment can be spatially dependent in
      multipartite plant viruses and highlights the use of evolutionary analyses to
      identify locations which could be actively managed to facilitate the prevention
      of outbreaks involving novel reassortant strains. 

PMID- 24944574
TI  - Open Access & ecancermedicalscience.

PMID- 24944572
TI  - Population-level effects of fitness costs associated with repressible female
      lethal transgene insertions in two pest insects.
AB  - Genetic control strategies offer great potential for the sustainable and
      effective control of insect pests. These strategies involve the field release of
      transgenic insects with the aim of introducing engineered alleles into wild
      populations, either permanently or transiently. Their efficacy can therefore be
      reduced if transgene-associated fitness costs reduce the relative performance of
      released insects. We describe a method of measuring the fitness costs associated
      with transgenes by analyzing their evolutionary trajectories when placed in
      competition with wild-type alleles in replicated cage populations. Using this
      method, we estimated lifetime fitness costs associated with two repressible
      female-lethal transgenes in the diamondback moth and olive fly as being
      acceptable for field suppression programs. Furthermore, using these estimates of
      genotype-level fitness costs, we were able to project longer-term evolutionary
      trajectories for the transgenes investigated. Results from these projections
      demonstrate that although transgene-associated fitness costs will ultimately
      cause these transgenes to become extinct, even when engineered lethality is
      repressed, they may persist for varying periods of time before doing so. This
      implies that tetracycline-mediated transgene field persistence in these strains
      is unlikely and suggests that realistic estimates of transgene-associated fitness
      costs may be useful in trialing 'uncoupled' gene drive system components in the
      field. 

PMID- 24944575
TI  - Cancer information on the Internet.

PMID- 24944571
TI  - Multiple introductions and recombination in Cryphonectria hypovirus 1:
      perspective for a sustainable biological control of chestnut blight.
AB  - Cryphonectria hypovirus 1 (CHV1) is a mycovirus which decreases the virulence of
      its fungal host Cryphonectria parasitica, the causal agent of chestnut blight
      recently introduced in Europe. The understanding of the evolutionary processes
      which have shaped CHV1 populations in Europe is required to develop a sustainable
      biocontrol strategy targeting chestnut blight and effective in European chestnut
      forests. To retrace the evolutionary history of CHV1, we analyzed sequences from
      two genomic regions on a collection of 55 CHV1 strains from France and northern
      Spain, two countries where multiple introductions of C. parasitica occurred.
      Several recombination events and variable selection pressures contributed to CHV1
      evolution, agreeing with a non-clock-like diversification rate. These two
      mechanisms may be at the origin of CHV1 population diversity observed in western
      Europe. Considering the actual prevalence of CHV1 and its association with host
      genotypes, multiple introductions of CHV1 may have occurred in Europe, some of
      them directly from Asia and some of them through North America. Although some
      viral strains remained with low frequency in their introduction area, multiple
      infections might have allowed homologous recombination within parental sequences.
      Some of these recombinant lineages are associated with the spread of CHV1 in
      European regions. 

PMID- 24944576
TI  - Breast cancer and pregnancy: a comparative analysis of a Chilean cohort.
AB  - INTRODUCTION: Recent reports show that pregnancy-associated breast cancer (PABC)
      survival is similar to that of non-pregnant young patients. We evaluate the
      characteristics and prognosis of PABC patients treated in our cancer centre.
      PATIENTS AND METHODS: We identified patients with invasive PABC who were treated
      between 1999 and May 2013 and compared their characteristics with a no PABC
      cohort of similar age. RESULTS: The prevalence of PABC was 1% (n = 17). The
      median age was 35 years (range: 29- 42 years). The initial tumour was suspected
      clinically in 93% of the cases. Total mastectomy rates were higher in women with
      PABC (78.6% versus 40.5%, p = 0.02), and more tumours in the PABC group were
      triple negative, epidermal growth factor type 2 (HER2)-positive, and at advanced
      stages; however, these differences were not statistically significant. While
      estimated overall survival at ten years was higher in the non-PABC group (75.5%
      versus 80.5%, p = 0.043), disease-specific survival (DSS) rate at ten years was
      not statistically different between groups (83.9% for PABC and 75.5% for
      unrelated pregnancy BC, p = 0.37). CONCLUSIONS: PABC is a rare event. In our
      cohort, it tended to be more aggressive. Compared with a similar age cohort, the
      DSS was not worse.

PMID- 24944577
TI  - Focal therapy in prostate cancer: the current situation.
AB  - Prostate cancer is one of the most significant pathologies in the field of
      urology. The adoption of screening strategies and improvements in biopsies have
      resulted in an increase in early-stage tumour detection. Radical global therapies
      provide very good oncological results in localised prostate cancer. However,
      excess treatment in low- and, in some cases, intermediate-risk groups affects the
      quality of life of these patients. In the case of localised prostate cancer,
      focal therapies offer a minimally invasive option with good results with respect
      to established treatments. Although this is currently not a standard treatment,
      it represents the therapeutic approach with the greatest potential. THIS
      LITERATURE REVIEW HAS THE FOLLOWING OBJECTIVES: to define selection criteria for
      patients who are candidates for focal therapy, to assess the current situation
      and results of the different therapeutic options, and to define procedures in
      cases of recurrence and for follow-ups. We concluded that focal therapy is a
      viable therapeutic alternative for localised prostate cancer, specifically
      cryosurgery and high-intensity targeted ultrasound, which have acceptable
      oncologic results and a lower comorbidity compared with global treatments.
      Studies with a high level of scientific evidence are still needed to validate
      these results. ACQUISITION OF EVIDENCE: A search was carried out on the Medline
      (PubMed), EMBASE, Web of Science and Cochrane databases of all papers published
      before 31 July 2013. We included clinical studies and literature reviews that
      evaluated primary focal therapy for prostate cancer confirmed by biopsy and
      excluded focal rescue therapy studies. The keywords used were focal therapy and
      prostate cancer. Initially, we found 42 articles; 15 studies were excluded
      because they did not meet the minimum criteria for inclusion. A total of 1350
      cases were treated throughout 27 studies.

PMID- 24944578
TI  - Overcoming inefficient cellobiose fermentation by cellobiose phosphorylase in the
      presence of xylose.
AB  - BACKGROUND: Cellobiose and xylose co-fermentation holds promise for efficiently
      producing biofuels from plant biomass. Cellobiose phosphorylase (CBP), an
      intracellular enzyme generally found in anaerobic bacteria, cleaves cellobiose to
      glucose and glucose-1-phosphate, providing energetic advantages under the
      anaerobic conditions required for large-scale biofuel production. However, the
      efficiency of CBP to cleave cellobiose in the presence of xylose is unknown. This
      study investigated the effect of xylose on anaerobic CBP-mediated cellobiose
      fermentation by Saccharomyces cerevisiae. RESULTS: Yeast capable of fermenting
      cellobiose by the CBP pathway consumed cellobiose and produced ethanol at rates
      61% and 42% slower, respectively, in the presence of xylose than in its absence.
      The system generated significant amounts of the byproduct 4-O-beta-d
      glucopyranosyl-d-xylose (GX), produced by CBP from glucose-1-phosphate and
      xylose. In vitro competition assays identified xylose as a mixed-inhibitor for
      cellobiose phosphorylase activity. The negative effects of xylose were
      effectively relieved by efficient cellobiose and xylose co-utilization. GX was
      also shown to be a substrate for cleavage by an intracellular beta-glucosidase.
      CONCLUSIONS: Xylose exerted negative impacts on CBP-mediated cellobiose
      fermentation by acting as a substrate for GX byproduct formation and a mixed
      inhibitor for cellobiose phosphorylase activity. Future efforts will require
      efficient xylose utilization, GX cleavage by a beta-glucosidase, and/or a CBP
      with improved substrate specificity to overcome the negative impacts of xylose on
      CBP in cellobiose and xylose co-fermentation.

PMID- 24944579
TI  - Choice of transcripts and software has a large effect on variant annotation.
AB  - BACKGROUND: Variant annotation is a crucial step in the analysis of genome
      sequencing data. Functional annotation results can have a strong influence on the
      ultimate conclusions of disease studies. Incorrect or incomplete annotations can
      cause researchers both to overlook potentially disease-relevant DNA variants and
      to dilute interesting variants in a pool of false positives. Researchers are
      aware of these issues in general, but the extent of the dependency of final
      results on the choice of transcripts and software used for annotation has not
      been quantified in detail. METHODS: This paper quantifies the extent of
      differences in annotation of 80 million variants from a whole-genome sequencing
      study. We compare results using the RefSeq and Ensembl transcript sets as the
      basis for variant annotation with the software Annovar, and also compare the
      results from two annotation software packages, Annovar and VEP (Ensembl's Variant
      Effect Predictor), when using Ensembl transcripts. RESULTS: We found only 44%
      agreement in annotations for putative loss-of-function variants when using the
      RefSeq and Ensembl transcript sets as the basis for annotation with Annovar. The
      rate of matching annotations for loss-of-function and nonsynonymous variants
      combined was 79% and for all exonic variants it was 83%. When comparing results
      from Annovar and VEP using Ensembl transcripts, matching annotations were seen
      for only 65% of loss-of-function variants and 87% of all exonic variants, with
      splicing variants revealed as the category with the greatest discrepancy. Using
      these comparisons, we characterised the types of apparent errors made by Annovar
      and VEP and discuss their impact on the analysis of DNA variants in genome
      sequencing studies. CONCLUSIONS: Variant annotation is not yet a solved problem.
      Choice of transcript set can have a large effect on the ultimate variant
      annotations obtained in a whole-genome sequencing study. Choice of annotation
      software can also have a substantial effect. The annotation step in the analysis
      of a genome sequencing study must therefore be considered carefully, and a
      conscious choice made as to which transcript set and software are used for
      annotation.

PMID- 24944581
TI  - A genome scale overexpression screen to reveal drug activity in human cells.
AB  - Target identification is a critical step in the lengthy and expensive process of
      drug development. Here, we describe a genome-wide screening platform that uses
      systematic overexpression of pooled human ORFs to understand drug mode-of-action
      and resistance mechanisms. We first calibrated our screen with the well
      characterized drug methotrexate. We then identified new genes involved in the
      bioactivity of diverse drugs including antineoplastic agents and biologically
      active molecules. Finally, we focused on the transcription factor RHOXF2 whose
      overexpression conferred resistance to DNA damaging agents. This approach
      represents an orthogonal method for functional screening and, to our knowledge,
      has never been reported before. 

PMID- 24944580
TI  - Genomic insights into the overlap between psychiatric disorders: implications for
      research and clinical practice.
AB  - Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive
      disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder
      are common and result in significant morbidity and mortality. Although currently
      classified into distinct disorder categories, they show clinical overlap and
      familial co-aggregation, and share genetic risk factors. Recent advances in
      psychiatric genomics have provided insight into the potential mechanisms
      underlying the overlap between these disorders, implicating genes involved in
      neurodevelopment, synaptic plasticity, learning and memory. Furthermore, evidence
      from copy number variant, exome sequencing and genome-wide association studies
      supports a gradient of neurodevelopmental psychopathology indexed by mutational
      load or mutational severity, and cognitive impairment. These findings have
      important implications for psychiatric research, highlighting the need for new
      approaches to stratifying patients for research. They also point the way for work
      aiming to advance our understanding of the pathways from genotype to clinical
      phenotype, which will be required in order to inform new classification systems
      and to develop novel therapeutic strategies. 

PMID- 24944582
TI  - Predicting targeted drug combinations based on Pareto optimal patterns of
      coexpression network connectivity.
AB  - BACKGROUND: Molecularly targeted drugs promise a safer and more effective
      treatment modality than conventional chemotherapy for cancer patients. However,
      tumors are dynamic systems that readily adapt to these agents activating
      alternative survival pathways as they evolve resistant phenotypes. Combination
      therapies can overcome resistance but finding the optimal combinations
      efficiently presents a formidable challenge. Here we introduce a new paradigm for
      the design of combination therapy treatment strategies that exploits the tumor
      adaptive process to identify context-dependent essential genes as druggable
      targets. METHODS: We have developed a framework to mine high-throughput
      transcriptomic data, based on differential coexpression and Pareto optimization,
      to investigate drug-induced tumor adaptation. We use this approach to identify
      tumor-essential genes as druggable candidates. We apply our method to a set of
      ER(+) breast tumor samples, collected before (n = 58) and after (n = 60)
      neoadjuvant treatment with the aromatase inhibitor letrozole, to prioritize genes
      as targets for combination therapy with letrozole treatment. We validate
      letrozole-induced tumor adaptation through coexpression and pathway analyses in
      an independent data set (n = 18). RESULTS: We find pervasive differential
      coexpression between the untreated and letrozole-treated tumor samples as
      evidence of letrozole-induced tumor adaptation. Based on patterns of
      coexpression, we identify ten genes as potential candidates for combination
      therapy with letrozole including EPCAM, a letrozole-induced essential gene and a
      target to which drugs have already been developed as cancer therapeutics. Through
      replication, we validate six letrozole-induced coexpression relationships and
      confirm the epithelial-to-mesenchymal transition as a process that is upregulated
      in the residual tumor samples following letrozole treatment. CONCLUSIONS: To
      derive the greatest benefit from molecularly targeted drugs it is critical to
      design combination treatment strategies rationally. Incorporating knowledge of
      the tumor adaptation process into the design provides an opportunity to match
      targeted drugs to the evolving tumor phenotype and surmount resistance.

PMID- 24944583
TI  - Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia.
AB  - BACKGROUND: Aberrant DNA methylation is frequently found in human malignancies
      including acute myeloid leukemia (AML). While most studies focus on later disease
      stages, the onset of aberrant DNA methylation events and their dynamics during
      leukemic progression are largely unknown. METHODS: We screened genome-wide for
      aberrant CpG island methylation in three disease stages of a murine AML model
      that is driven by hypomorphic expression of the hematopoietic transcription
      factor PU.1. DNA methylation levels of selected genes were correlated with
      methylation levels of CD34+ cells and lineage negative, CD127-, c-Kit+, Sca-1+
      cells; common myeloid progenitors; granulocyte-macrophage progenitors; and
      megakaryocyte-erythroid progenitors. RESULTS: We identified 1,184 hypermethylated
      array probes covering 762 associated genes in the preleukemic stage. During
      disease progression, the number of hypermethylated genes increased to 5,465 in
      the late leukemic disease stage. Using publicly available data, we found a
      significant enrichment of PU.1 binding sites in the preleukemic hypermethylated
      genes, suggesting that shortage of PU.1 makes PU.1 binding sites in the DNA
      accessible for aberrant methylation. Many known AML associated genes such as
      RUNX1 and HIC1 were found among the preleukemic hypermethylated genes. Nine novel
      hypermethylated genes, FZD5, FZD8, PRDM16, ROBO3, CXCL14, BCOR, ITPKA, HES6 and
      TAL1, the latter four being potential PU.1 targets, were confirmed to be
      hypermethylated in human normal karyotype AML patients, underscoring the
      relevance of the mouse model for human AML. CONCLUSIONS: Our study identified
      early aberrantly methylated genes as potential contributors to onset and
      progression of AML.

PMID- 24944584
TI  - Circulating tumor DNA moves further into the spotlight.
AB  - Assessment of somatic genomic alterations from tumors can now be performed by
      sequencing circulating tumor DNA from the cell-free component of blood. This
      procedure, which identifies tumor-derived somatic mutations from a simple blood
      sample, circumvents the need for tumor tissue. A recent study highlights the
      promise of circulating tumor DNA to guide therapeutic decisions in a variety of
      solid tumors for both clinical and investigative purposes, as well as providing a
      tool for the early detection of cancer. 

PMID- 24944585
TI  - C2c: turning cancer into chronic disease.

PMID- 24944586
TI  - ELSI practices in genomic research in East Asia: implications for research
      collaboration and public participation.
AB  - Common infrastructures and platforms are required for international
      collaborations in large-scale human genomic research and policy development, such
      as the Global Alliance for Genomics and Health and the 'ELSI 2.0' initiative.
      Such initiatives may require international harmonization of ethical and
      regulatory requirements. To enable this, however, a greater understanding of
      issues and practices that relate to the ethical, legal and social implications
      (ELSI) of genomic research will be needed for the different countries and global
      regions involved in such research. Here, we review the ELSI practices and
      regulations for genomic research in six East Asian countries (China, Indonesia,
      Japan, Singapore, South Korea and Taiwan), highlighting the main similarities and
      differences between these countries, and more generally, in relation to Western
      countries. While there are significant differences in ELSI practices among these
      East Asian countries, there is a consistent emphasis on advancing genomic science
      and technology. In addition, considerable emphasis is placed on informed consent
      for participation in research, whether through the contribution of tissue samples
      or personal information. However, a higher level of engagement with interested
      stakeholders and the public will be needed in some countries. 

PMID- 24944587
TI  - Genome-wide mutational landscape of mucinous carcinomatosis peritonei of
      appendiceal origin.
AB  - BACKGROUND: Mucinous neoplasms of the appendix (MNA) are rare tumors which may
      progress from benign to malignant disease with an aggressive biological behavior.
      MNA is often diagnosed after metastasis to the peritoneal surfaces resulting in
      mucinous carcinomatosis peritonei (MCP). Genetic alterations in MNA are poorly
      characterized due to its low incidence, the hypo-cellularity of MCPs, and a lack
      of relevant pre-clinical models. As such, application of targeted therapies to
      this disease is limited to those developed for colorectal cancer and not based on
      molecular rationale. METHODS: We sequenced the whole exomes of 10 MCPs of
      appendiceal origin to identify genome-wide somatic mutations and copy number
      aberrations and validated significant findings in 19 additional cases. RESULTS:
      Our study demonstrates that MNA has a different molecular makeup than colorectal
      cancer. Most tumors have co-existing oncogenic mutations in KRAS (26/29) and GNAS
      (20/29) and are characterized by downstream PKA activation. High-grade tumors are
      GNAS wild-type (5/6), suggesting they do not progress from low-grade tumors. MNAs
      do share some genetic alterations with colorectal cancer including gain of 1q
      (5/10), Wnt, and TGFbeta pathway alterations. In contrast, mutations in TP53
      (1/10) and APC (0/10), common in colorectal cancer, are rare in MNA. Concurrent
      activation of the KRAS and GNAS mediated signaling pathways appears to be shared
      with pancreatic intraductal papillary mucinous neoplasm. CONCLUSIONS: MNA genome
      wide mutational analysis reveals genetic alterations distinct from colorectal
      cancer, in support of its unique pathophysiology and suggests new targeted
      therapeutic opportunities.

PMID- 24944588
TI  - Challenging role of Wnt5a and its signaling pathway in cancer metastasis
      (Review).
AB  - Wnt5a is a noncanonical signaling member of the wingless-related/mouse mammary
      tumor virus integration family, which is involved in a wide range of cellular
      processes, particularly in cancer development and metastasis. Accumulating
      evidence indicates that Wnt5a exhibits paradoxical effects in various types of
      cancer metastasis. Therefore, the Wnt5a signaling cascade in cancer metastasis
      appears to be complex and may depend on binding receptors, downstream effectors,
      exogenous inhibitors and tumor microenvironments, as well as the extracellular
      matrix, particularly cell/tissue-tropic contexts. The aim of the present study
      was to summarize the previous findings on the roles of Wnt5a and the potential
      mechanisms in various types of cancer metastasis. Furthermore, it is reasonable
      to hypothesize that Wnt5a and the involved signaling pathways may become
      molecular targets in the treatment of cancer metastasis.

PMID- 24944589
TI  - Effect of Yangyinqingfei decoction on radiation-induced lung injury via
      downregulation of MMP12 and TIMP-1 expression.
AB  - The aim of this study was to evaluate the effect and underlying mechanism of
      Yangyinqingfei decoction on radiation-induced lung injury in rats. Wistar rats
      (n=75) were randomly divided into five experimental groups (A-E). Rats in two of
      the groups were administered saline solution, whereas rats in the remaining three
      groups were administered different doses of Yangyinqingfei decoction. After one
      week, the rats were irradiated with a single dose of 25 Gy to their right hemi
      thoraxes by a 60Co gamma-ray, with the exception of the control group, which
      underwent sham irradiation. The effect of Yangyinqingfei decoction was assessed
      one, two and four weeks post-irradiation according to the pathological changes
      and the right lung index (wet weight of right lung/body weight *100%). Expression
      levels of matrix metalloproteinase-12 (MMP-12) and tissue inhibitors of
      metalloproteinases-1 (TIMP-1) in lung tissue were determined using the reverse
      transcription-polymerase chain reaction and western blot analysis. Pretreatment
      with Yangyinqingfei resulted in a significant dose-dependent resistance to
      radiation-induced body weight loss. The expression of MMP-12 and TIMP-1 increased
      following irradiation. However, the levels of MMP-12 and TIMP-1 in groups
      receiving Yangyinqingfei were lower four weeks after irradiation compared with
      those in rats administered saline. Cumulatively, these results suggest that
      Yangyinqingfei has a protective effect on radiation-induced lung injury in rats,
      possibly by downregulating MMP-12 and TIMP-1 expression.

PMID- 24944590
TI  - Histone preconditioning protects against obstructive jaundice-induced liver
      injury in rats.
AB  - A major consequence of obstructive jaundice (OJ) in clinical practice is the
      development of severe liver injury, and at present, no effective treatments have
      been developed to protect against it. Preconditioning with damage-associated
      molecular pattern (DAMP) molecules has been demonstrated to protect multiple
      organs from injury, and histones have been recently identified as DAMP molecules.
      The aim of the present study was to investigate the protective effect of histone
      preconditioning against OJ-induced liver injury in rats and the involvement of
      Toll-like receptors. Rats were administered histone proteins (200 MUg/kg; 1 ml)
      or physiological saline (1 ml) intraperitoneally 24 h prior to being subjected to
      bile duct ligation (BDL). The serum levels of liver enzymes and bilirubin, as
      well as the histopathology were analyzed. The mRNA expression of interleukin-6
      (IL-6) in the liver tissue was analyzed using quantitative polymerase chain
      reaction. BDL in the control group caused severe OJ-induced liver injury, as
      indicated by the significantly elevated levels of liver enzymes and mRNA levels
      of IL-6, and confirmed by histopathological alterations. However, histone
      preconditioning significantly ameliorated the OJ-induced liver injury caused by
      BDL, as shown by an improvement in the levels of liver enzymes, a suppression of
      IL-6 production, as well as histopathological alterations. Therefore, these
      results suggested that histone preconditioning is able to protect against OJ
      induced liver injury in rats.

PMID- 24944591
TI  - Analysis of association between brain natriuretic peptide levels and blood
      pressure variability.
AB  - The present study aimed to investigate the association between plasma brain
      natriuretic peptide (BNP) levels and systolic blood pressure (SBP) variability
      over a one-year period. Blood pressure was measured in 44 patients treated for
      hypertension (73+/-9 years old) at an outpatient clinic every one to two months
      over a one-year period. The standard deviation (SD) and the coefficient of
      variation (CV) were calculated to assess SBP variability. Mean SBP was also
      calculated over the year. Plasma BNP levels were measured at the end of the one
      year period. BNP was found to correlate with mean SBP (r=0.599; P<0.001).
      However, BNP was not observed to be correlate with either the SD (r=0.219;
      P=0.153) or the CV (r=0.058; P=0.709) of the SBP. Multiple regression analysis
      revealed that only the mean values of SBP were independently associated with BNP
      (beta=0.613; P<0.001). Thus, BNP was found to be correlated with mean SBP, but
      not SBP variability. In conclusion, plasma BNP levels may reflect the average
      SBP, but not SBP variability over the one-year period prior to the measurement of
      BNP in patients with hypertension.

PMID- 24944592
TI  - Clinical findings of 40 patients with nocardiosis: A retrospective analysis in a
      tertiary hospital.
AB  - To the best of our knowledge, no Chinese case studies concerning Nocardia
      infection have been published to date. Therefore, the present study aimed to
      retrospectively evaluate the risk factors, clinical features, imaging results,
      laboratory abnormalities, treatments and outcomes of nocardiosis in a Chinese
      tertiary hospital. Data collected from patients with laboratory-confirmed
      nocardiosis were retrospectively analyzed. A total of 40 patients who had a
      positive culture of Nocardia were included. The median time between the onset of
      symptoms and diagnosis was 42 days. Underlying diseases were identified in 72.5%
      of the patients of which diabetes was the most common (32.5%). The most important
      risk factor was corticosteroid administration. Fever and cough were common
      clinical symptoms. The pleuropulmonary (85%) were the most frequently involved
      sites and the disseminated disease rate was 30.0%. Frequent chest computed
      tomography scans revealed the presence of airspace opacities, nodules and masses,
      in addition to cavitary lesions that were particularly common among the study
      group. Brain images revealed lesions associated with abscesses. The majority of
      the patients (71.1%) were treated with trimethoprim sulfamethoxazole alone or in
      combination with other drugs. The in-hospital mortality rate was 15.0%.
      Disseminated disease, immunocompromised patients, an older age, brain involvement
      and concomitant infections were associated with a poor prognosis. Nocardiosis is
      an uncommon but emerging disease. The present study reports the first case series
      on nocardiosis from China and provides important information on the clinical
      features and risk factors of nocardiosis. Early recognition of the disease and
      the initiation of appropriate treatment are essential for a good prognosis.

PMID- 24944593
TI  - Inhibitory effect of rape pollen supercritical CO2 fluid extract against
      testosterone-induced benign prostatic hyperplasia in rats.
AB  - Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape
      pollen is an apicultural product that is composed of nutritionally valuable and
      biologically active substances. The aim of the present study was to investigate
      the protective effect of rape pollen supercritical CO2 fluid extract (SFE-CO2) in
      BPH development using a testosterone-induced BPH rat model. BPH was induced in
      the experimental groups by daily subcutaneous injections of testosterone for a
      period of 30 days. Rape pollen SFE-CO2 was administered daily by oral gavage
      concurrently with the testosterone injections. Animals were sacrificed at the
      scheduled termination and the prostates were weighed and subjected to
      histopathological examination. Testosterone, dihydrotestosterone (DHT), 5alpha
      reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced
      animals exhibited an increase in prostate weight with increased testosterone,
      DHT, 5alpha-reductase and COX-2 expression levels. However, rape pollen SFE-CO2
      treatment resulted in significant reductions in the prostate index and
      testosterone, DHT, 5alpha-reductase and COX-2 levels compared with those in BPH
      induced animals. Histopathological examination also demonstrated that rape pollen
      SFE-CO2 treatment suppressed testosterone-induced BPH. These observations
      indicate that rape pollen SFE-CO2 inhibits the development of BPH in rats and
      these effects are closely associated with reductions in DHT, 5alpha-reductase and
      COX-2 levels. Therefore, the results of the present study clearly indicate that
      rape pollen SFE-CO2 extract may be a useful agent in BPH treatment.

PMID- 24944594
TI  - Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein
      endothelial cell injury induced by hydrogen peroxide and the effect on the NO
      cGMP signaling pathway.
AB  - The aim of the present study was to evaluate the protective effect of the
      ultrafiltration extract of Xin Mai Jia (XMJ) on a human umbilical vein
      endothelial cell (HUVEC) injury model induced by hydrogen peroxide (H2O2), by
      providing experimental data to investigate the mechanism and efficacy underlying
      the therapeutic effects on atherosclerosis. HUVECs were first injured by H2O2 and
      then varying final concentrations of the Chinese herb extract were added. Effects
      of the XMJ extract on morphology, activity, monolayer permeability, biochemical
      indicators, cytokines, endothelial nitric oxide synthase (eNOS) protein content
      and eNOS gene expression in the HUVECs were analyzed. H2O2 significantly promoted
      HUVEC injury. The XMJ ultrafiltration extract significantly improved the
      morphological changes in the injured HUVECs. In addition, XMJ treatment increased
      cell activity and decreased monolayer permeability. The expression levels of
      intracellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1
      and -6 and nuclear factor-kappaB decreased, while the expression levels of matrix
      metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 increased with
      XMJ administration. Increased levels of nitric oxide (NO), eNOS protein and eNOS
      gene expression were also observed. Therefore, the XMJ ultrafiltration extract
      exhibits marked anti-inflammatory effects and antioxidant abilities. These
      properties significantly inhibited the H2O2-induced injury of HUVECs, which may
      be associated with the NO-cyclic guanosine monophosphate signaling pathway.

PMID- 24944595
TI  - Eosinophilic cystitis in a patient with hypereosinophila syndrome: A case report.
AB  - Hypereosinophilic syndrome (HES) is a rare disorder that is characterized by
      hypereosinophilia and organ damage, caused by the infiltration of eosinophils. In
      rare cases, the urinary bladder may also be involved. The current case report
      presented a 56-year-old male with gross hematuria and hypereosinophilia. The
      diagnosis of eosinophilic cystitis associated HES was established. Oral
      prednisone with a slow tapering regimen was administered as the primary treatment
      for the patient, which achieved partial hematological remission and complete
      relief of cystitis during a six-month follow-up period. Although eosinophilic
      cystitis is not commonly the primary manifestation of HES, eosinophilic cystitis
      should be taken into consideration following the onset of urinary symptoms in
      patients with HES.

PMID- 24944596
TI  - TGF-beta1 induces the formation of vascular-like structures in embryoid bodies
      derived from human embryonic stem cells.
AB  - Human embryonic stem cells (ESCs) can differentiate into endothelial cells in
      response to stimuli from extracellular cytokines. Transforming growth factor
      (TGF)-beta1 signaling is involved in stem cell renewal and vascular development.
      Previously, human ESCs were isolated from inner cell mass and a stable ESC line
      was developed. In the present study, the effects of extracellular TGF-beta1 were
      investigated on human ESC-derived embryoid bodies (EB) in suspension. The
      structures of the EBs were analyzed with light and electron microscopy, while the
      cellular composition of the EBs was examined via the expression levels of
      specific markers. Vascular-like tubular structures and cardiomyocyte-like beating
      cells were observed in the EBs at day 3 and 8, respectively. The frequencies of
      vascular-like structures and beating cells in the TGF-beta1 treated group were
      significantly higher compared with the control group (84.31 vs. 12.77%; P<0.001;
      37.25 vs. 8.51%; P<0.001, respectively). Electron microscopy revealed the
      presence of lumens and gap junctions in the sections of the tubular structures.
      Semiquantitative polymerase chain reaction revealed elevated expression levels of
      CD31 and fetal liver kinase-1 in EBs cultured with TGF-beta1. In addition,
      extensive staining of von Willebrand factor was observed in the vascular-like
      structures of TGF-beta1-treated EBs. Therefore, the results of the present study
      may aid the understanding of the underlying mechanisms of human ESC
      differentiation and improve the methods of propagating specific cell types for
      the clinical therapy of cardiovascular diseases.

PMID- 24944597
TI  - Green tea catechin, epigallocatechin-3-gallate, attenuates the cell viability of
      human non-small-cell lung cancer A549 cells via reducing Bcl-xL expression.
AB  - Clinical and epidemiological studies have indicated that the consumption of green
      tea has a number of beneficial effects on health. Epigallocatechin-3-gallate
      (EGCg), the major polyphenolic compound present in green tea, has received much
      attention as an active ingredient. Among the numerous promising profiles of EGCg,
      the present study focused on the anticancer effects. Apoptosis induced by EGCg
      and subsequent cell growth suppression have been demonstrated in a number of cell
      culture studies. However, the underlying mechanism of apoptotic cell death
      remains unclear. Thus, the aim of the present study was to identify the major
      molecule that mediates proapoptotic cell death by EGCg. The effect of EGCg on
      cell proliferation and the induction of mRNA that modulates apoptotic cell death
      was evaluated in the A549 human non-small-cell lung cancer cell line. In
      addition, morphological changes were assessed by microscopy in A549 cells that
      had been treated with 100 MUM EGCg for 24 h. The MTT assay revealed that cell
      proliferation was significantly reduced by EGCg in a dose-dependent manner (3-100
      MUM). The mRNA expression level of B-cell lymphoma-extra large (Bcl-xL) was
      decreased in A549 cells following 24 h incubation with 100 MUM EGCg. Therefore,
      the results indicated that the inhibition of cell proliferation by EGCg may be
      achieved via suppressing the expression of the cell death-inhibiting gene, Bcl
      xL.

PMID- 24944598
TI  - Thrombus formation induced by laser in a mouse model.
AB  - Animal models are used for the development of techniques and/or models that aid
      the study of thrombosis pathophysiology. The aim of the present study was to
      modify the technique of in vivo thrombosis induction to make it more accessible.
      BALB/c mice were intraperitoneally anesthetized with 0.4 ml 2,2,2-tribromoethanol
      (266.6 mg/kg) and xylazine (13.3 mg/kg), whilst maintaining stable blood pressure
      and temperature. Through abdominal surgery, the mesentery was identified and
      isolated for the visualization of the arteries. A simple epifluorescence
      magnifier was used to detect the presence of thrombi. The results obtained
      indicate that using rose bengal at concentrations of 25 and 50 mg/kg and a laser
      power of 5 mW, thrombus formation occurred. In addition, formation of the
      thrombus occurred ~30 min following induction and the thrombus had a total area
      of 4,878.3 MUm2, which caused total occlusion of the mesenteric artery. For
      visualization, platelets were labeled with calcein acetyloxymethyl ester for 1 h,
      which resulted in improved observation of thrombus formation in real time.
      Therefore, this technique may be used to perform in vivo studies simply and at
      low cost, and is suitable for use in a variety of studies of thrombosis.

PMID- 24944599
TI  - 18F-FLT PET/CT imaging in a Wister rabbit inflammation model.
AB  - The aim of the present study was to determine the tumour specificity of the newly
      developed nucleoside metabolic positron emission tomography (PET) tracer, 3'
      deoxy-3'-18F-fluorothymidine (18F-FLT). Using 18F-FLT PET imaging, DNA synthesis
      and cell proliferation were detected in Staphylococcus aureus (S. aureus) abscess
      and calcium sulphate models in Wister rabbits. A total of eight rabbits were
      implanted with S. aureus in the left tibia to induce an inflammatory process.
      Calcium sulphate + gentamicin was implanted in the right tibia to induce a
      physical stimulus without bacterial multiplication. After four weeks, the animals
      underwent 18F-FLT PET imaging, bacterial culturing and tissue pathology. The
      uptake of 18F-FLT was significantly higher in the abscess site compared with that
      in the granuloma, with maximum standardised uptake values of 5.76+/-0.25 and
      1.15+/-0.32, respectively (P<0.01). This indicates that 18F-FLT is not a specific
      tumour tracer since active inflammation also results in the uptake of this
      compound. However, the tumour specificity of this tracer is higher compared with
      that of 18F-fluorodeoxyglucose. Therefore, 18F-FLT may be useful in the
      differential diagnosis of benign and malignant tumours.

PMID- 24944600
TI  - High dosage of agmatine alleviates pentylenetetrazole-induced chronic seizures in
      rats possibly by exerting an anticonvulsive effect.
AB  - The aim of the present study was to investigate the mechanism underlying the
      effects of different doses of agmatine in rats with chronic epilepsy. To generate
      chronic epilepsy models, rats pretreated with different doses of agmatine (20, 40
      and 80 mg/kg) were intraperitoneally injected with pentylenetetrazole (35 mg/kg)
      for 28 consecutive days. Epileptic behavior was observed using behavioral
      measurements of convulsion for 1 h after each treatment with pentylenetetrazole.
      Morphological alterations of the hippocampal neurons were also observed using
      hematoxylin and eosin staining. In addition, the expression levels of glial
      fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the
      hippocampus were detected by immunohistochemistry. Furthermore, reverse
      transcription polymerase chain reaction was performed to detect the mRNA
      expression of two subunits (NR1 and NR2B) of the N-methyl-D-aspartic acid (NMDA)
      receptor in the rat hippocampus. The results demonstrated that administration of
      agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic
      seizures and also reduced neuronal loss and astrocyte hyperplasia in the
      hippocampal area. Furthermore, agmatine (80 mg/kg) affected the mRNA expression
      levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect
      on the expression of iNOS in the hippocampus. Higher doses of agmatine inhibited
      the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and
      neuronal damage in the hippocampus caused by seizures and selectively reduced the
      expression of the NR1 subunit of NMDA. Our results suggest that agmatine has an
      anticonvulsive effect in chronic epilepsy.

PMID- 24944601
TI  - Ethanol extract of Cirsium japonicum attenuates hepatic lipid accumulation via
      AMPK activation in human HepG2 cells.
AB  - One of the most common causes of chronic liver disease, nonalcoholic fatty liver
      disease (NAFLD), is strongly associated with obesity and dysregulated insulin
      action in the liver. However, there are no pharmacological agents currently
      established for the treatment of NAFLD. A flowering plant in the Asteraceae
      family, Cirsium japonicum (CJ), exhibits a variety of pharmacological and
      antioxidative properties that promote hepatoprotection. In the present study, CJ
      ethanol extract was shown to reduce hepatic triglyceride (TG) and cholesterol
      accumulation. CJ significantly increased AMP-activated protein kinase (AMPK)
      phosphorylation in HepG2 hepatocytes and downregulated the level of the target
      genes, acetyl-CoA carboxylase and fatty acid synthase. In addition, CJ
      upregulated the expression of carnitine palmitoyltransferase-1, which is involved
      in fatty acid oxidation. The results of the present study indicated that the
      positive effects of CJ extract on high-fat diet-induced hepatic TG accumulation
      were mediated via the AMPK signaling pathway, indicating a potential target for
      the preventative treatment of NAFLD.

PMID- 24944602
TI  - Arsenic trioxide induces apoptosis in the THP1 cell line by downregulating EVI-1.
AB  - Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the
      current study, the effects of arsenic trioxide (ATO) on the ecotropic viral
      integration site-1 (EVI-1) gene were investigated in the THP1 cell line. THP-1
      cells were treated with different concentrations of ATO (0, 1, 3 and 5 MUM) for
      24, 48 or 72 h, then tested for cell viability by CCK-8 kit, cell morphology by
      cytospin smear, cell apoptosis by flow cytometry, EVI-1 mRNA expression by
      reverse transcription polymerase chain reaction (RT-PCR) and protein quantity by
      western blot. ATO treatment was shown to inhibit proliferation and induce
      apoptosis in THP1 cells in a dose- and time-dependent manner. ATO downregulated
      the mRNA and protein expression of EVI-1 in the THP1 cell line. In addition, ATO
      significantly decreased the expression of antiapoptotic proteins, B-cell lymphoma
      2 (Bcl-2) and B cell lymphoma-extra large (Bcl-xL), but markedly increased the
      expression of proapoptotic proteins, including c-Jun N-terminal kinase (JNK),
      phosphorylated-JNK, Bax, full length caspase-3 and cleaved caspase-3. These
      results indicated that ATO inhibited the proliferation and induced apoptosis in
      THP1 cells partially via blocking the inhibitory effects of EVI-1 on the JNK
      signaling pathway with the involvement of apoptosis-associated proteins,
      including Bax, Bcl-2, Bcl-xL and caspase-3. These novel observations may be used
      to elucidate the mechanism by which ATO induces apoptosis in acute leukemia
      cells, and provide rationales to develop a personalized medicine strategy for ATO
      via targeting EVI-1 positive neoplasm.

PMID- 24944604
TI  - NF-kappaB inhibition alleviates carbon tetrachloride-induced liver fibrosis via
      suppression of activated hepatic stellate cells.
AB  - An effective treatment for hepatic fibrosis is not available clinically. Nuclear
      factor (NF)-kappaB plays a central role in inflammation and fibrosis. The aim of
      the present study was to investigate the effect of an NF-kappaB inhibitor, BAY-11
      7082 (BAY), on mouse liver fibrosis. The effects of BAY on hepatic stellate cell
      (HSC) activation were measured in the lipopolysaccharide-activated rat HSC-T6
      cell line. In addition, the therapeutic effect of BAY was studied in vivo using a
      model of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice. BAY
      effectively decreased the cell viability of activated HSC-T6 cells and suppressed
      HSC-T6 activation by downregulating the expression of collagen I and alpha-smooth
      muscle actin. BAY significantly inhibited the phosphorylation of
      phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B
      (Akt) in activated HSC-T6 cells. In addition, administration of BAY attenuated
      mouse liver fibrosis induced by CCl4, as shown by histology and the expression of
      profibrogenic markers. BAY also significantly decreased the levels of serum
      alanine aminotransferase in this model of hepatic fibrosis. Therefore, the
      results of the present study demonstrate that BAY attenuates liver fibrosis by
      blocking PI3K and Akt phosphorylation in activated HSCs. Thus, BAY demonstrates
      therapeutic potential as a treatment for hepatic fibrosis.

PMID- 24944603
TI  - Chromophobe renal cell carcinoma associated with eosinophilia: A report of three
      cases.
AB  - Eosinophilia is typically associated with allergic reactions, parasitic
      infestations, certain forms of vasculitis, the use of certain medications and
      hematologic malignancies. In addition to eosinophilia associated with
      gastrointestinal tumors, lung cancer and thyroid carcinoma in solid malignancies,
      there are a limited number of cases describing peripheral hypereosinophilia in
      urologic tumors. The present study reports three cases of eosinophilia in
      patients with chromophobe renal cell carcinoma (CRCC) and investigates the
      association between excessive eosinophilia and the recurrence and prognosis of
      renal carcinoma. This is the first report of CRCC associated with excessive
      eosinophilia. Eosinophilia following tumor resectioning may indicate a poor
      prognosis, tumor recurrence and rapid disease progression.

PMID- 24944605
TI  - A novel NF-kappaB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice.
AB  - Nuclear factor (NF)-kappaB is strongly associated with the development of immune
      regulation and inflammation. The aim of the present study was to identify whether
      a NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), ameliorates
      systemic lupus erythematosus (SLE) in a pristane-induced mouse model. SLE was
      induced in 8-week-old female BALB/c mice by the injection of 0.5 ml pristane. The
      therapeutic effect of 12 mg/kg DHMEQ on the pristane-induced BALB/c mouse model
      of lupus was investigated to elucidate the effects on SLE. The intraperitoneal
      administration of DHMEQ three times per week was initiated when the mice were 16
      weeks-old (8 weeks following the pristane injection) and the treatment was
      continued for 16 weeks. Serum IgG autoantibodies against nucleosomes, dsDNA and
      histones were detected at weeks 8, 16 and 32. In addition, the expression levels
      of interleukin (IL)-1beta, 6 and 17, as well as tumor necrosis factor (TNF)
      alpha, were analyzed at week 32. Renal lesions were also observed. DHMEQ was
      shown to antagonize the increasing levels of anti-nucleosome, anti-dsDNA and anti
      histone autoantibodies, as well as the increasing levels of IL-1beta, 6 and 17
      and TNF-alpha. In addition, DHMEQ reduced the number of renal lesions caused by
      pristane, as reflected by milder proteinuria and reduced renal pathology. The
      renal expression levels of phosphorylated-p38 mitogen-activated protein kinase
      (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-kappaB p65 were
      significantly downregulated. Therefore, the results of the present study indicate
      that DHMEQ has a beneficial effect on pristane-induced lupus through regulating
      cytokine levels and the MAPK/JNK/NF-kappaB signaling pathway.

PMID- 24944606
TI  - Olmesartan medoxomil reverses glomerulosclerosis in renal tissue induced by
      myocardial infarction without changes in renal function.
AB  - The aim of the present study was to investigate the effect of olmesartan
      medoxomil (OLM) on renal injury in mice with myocardial infarction (MI). A total
      of 33 male C57/BL/6 mice were divided into a sham surgery group (SHAM group), MI
      group (MI group) and OLM treatment group (OLM group). Experimental MI models were
      established in the mice of the MI and OLM groups by coronary artery ligation, and
      the mice in the OLM group were fed a daily dose of 10 mg/kg OLM for eight weeks.
      The results showed that MI induced a reduction in cardiac function and an
      increase in systolic blood pressure. In addition, increased periodic acid-Schiff
      (PAS) positive staining, combined with increased levels of angiotensin II (Ang
      II) in the plasma and kidneys, and increased expression levels of renin,
      angiotensin II type 1 receptor (AT1R) and angiotensinogen (AGT) in the kidney
      tissues was observed compared with those in the SHAM group. OLM treatment
      attenuated the injury by reducing the systolic blood pressure and PAS positive
      staining, and decreasing the expression levels of Ang II, renin, AT1R and AGT in
      the kidney compared with those in the MI group. It may be concluded that MI
      activates the intrarenal renin-angiotensin system and leads to
      glomerulosclerosis, and that OLM protects the kidney by inhibiting the effects of
      Ang II.

PMID- 24944608
TI  - Direct identification of Mycobacterium abscessus through 16S rDNA sequence
      analysis and a citrate utilization test: A case report.
AB  - A growing number of nontuberculous mycobacteria infection cases, especially those
      caused by rapidly growing mycobacteria (RGM), have been reported in the past
      decade. Conventional methods for mycobacteria diagnosis are inefficient and
      easily lead to misdiagnosis. New detection methods, such as gene sequencing, have
      been reported but are not widely used. The aim of the present case report was to
      provide a quick and exact method of identifying Myobacterium abscessus (M.
      abscessus) infections. The particular case reported in this study initially
      manifested as hyperglycemia and papules in the right leg. Routine cultures for
      fungus were repeatedly negative. However, cultures of the purulent material under
      aerobic cultivation for five days yielded a rapidly growing, nontuberculous
      mycobacterium. A Ziehl-Neelsen staining of this mycobacterium revealed the
      presence of acid-fast bacilli that were finally identified as M. abscessus
      through 16S rDNA sequence analysis and a citrate utilization test. The current
      report may help other clinicians to make a quick and accurate diagnosis of RGM
      infection.

PMID- 24944607
TI  - Analysis of differentially expressed genes in cold-exposed mice to investigate
      the potential causes of cold-induced hypertension.
AB  - Cold exposure is considered to be an important contributing factor to the high
      morbidity of hypertension. In order to elucidate the cause and mechanism of cold
      induced hypertension (CIH), gene expression analysis was performed on microarray
      data for two groups of cold-exposed mice (4 degrees C for 1 week and 4 degrees C
      for 5 weeks, three replicates per group) and their respective control groups
      maintained at 30 degrees C. Analysis results indicated that the differentially
      expressed genes with the most significance were associated with adaptive
      thermogenesis, fatty acid metabolism and energy metabolism. The expected marked
      increase in metabolism during cold exposure caused tissue hypoxia. Genes involved
      in the hypoxia-inducible factor signaling pathway were activated. In addition,
      genes associated with oxidative stress were significantly upregulated, including
      superoxide dismutase 2 (SOD2) and epoxide hydrolase 2 (EPHX2). The majority of
      genes involved in inflammation-associated pathways were shown to be downregulated
      in the 4 degrees C 5-week group. Therefore, the results of the present study
      indicate that tissue hypoxia and increased oxidative stress may play important
      roles in the process of CIH.

PMID- 24944609
TI  - Qianliening capsule inhibits benign prostatic hyperplasia angiogenesis via the
      HIF-1alpha signaling pathway.
AB  - Angiogenesis plays an important role in the progression and development of benign
      prostatic hyperplasia (BPH), and has become a promising target for BPH treatment.
      The hypoxia-inducible factor-1alpha (HIF-1alpha) signaling pathway promotes the
      process of angiogenesis, contributing to the growth and progression of a number
      of hyperplasia diseases, including BPH. Qianliening capsule (QC) is a traditional
      Chinese formula that has been used clinically in China to treat BPH for a number
      of years. Recently, QC was demonstrated to inhibit prostatic cell growth and
      induce apoptosis in vivo and in vitro via regulating the epidermal growth
      factor/signal transducer and activator of transcription 3 signaling pathway and
      mitochondrion-dependent apoptosis pathway. However, the mechanisms underlying the
      anti-BPH effect remain largely unknown. To further elucidate the mechanism of QC
      activity in BPH treatment, a rat BPH model established by injecting testosterone
      following castration was established and the effect of QC on prostatic tissue
      angiogenesis was evaluated, as well as the underlying molecular mechanisms. QC
      was shown to reduce the prostatic index in BPH rats, but without affecting the
      body weight, demonstrating that QC is effective in the treatment of BPH and
      without apparent toxicity. In addition, QC treatment significantly reduced the
      intraprostatic microvessel density, indicating antiangiogenesis activity in vivo.
      In addition, treatment with QC inhibited the expression of HIF-1alpha in BPH
      rats, as well as the expression of vascular endothelial growth factor and basic
      fibroblast growth factor. Therefore, for the first time, the present study
      hypothesized that QC inhibits angiogenesis in prostatic tissue of BPH rats via
      the inhibition of the HIF-1alpha signaling pathway, which may be one of the
      mechanisms in which QC treats BPH.

PMID- 24944610
TI  - Thrombocytosis is a significant indictor of hypercoagulability, prognosis and
      recurrence in gastric cancer.
AB  - Although thrombocytosis has been reported in a variety of cancer types, the
      standard of thrombocytosis in gastric cancer (GC) and the association between
      thrombocytosis and the clinicopathological features of patients with GC remain
      unclear. In the present study, 1,763 GC patients were retrospectively filtered by
      preoperative thrombocytosis and compared with control group A (n=107) that had
      benign gastric lesions and control group B (n=100) that were GC patients with a
      normal platelet (PLT) count. Associations between clinical variables and
      preoperative PLT counts were assessed by univariate and multivariate analyses.
      Kaplan-Meier survival curves and Cox regression were used to evaluate the effect
      of thrombocytosis on prognosis. Sensitivities and specificities of the PLT counts
      in predicting recurrence were analyzed via area under the receiver operating
      characteristic curve (AUROC). The results indicated that the incidence of
      thrombocytosis in GC patients was higher than in benign gastric lesion patients,
      with 4.03% of GC patients having a PLT count >400*109/l (P=0.014) and 12.08% had
      a PLT count >300*109/l (P<0.001). For the patients with a PLT count >400*109/l,
      the frequency of abnormal PLT counts in GC correlated with tumor size (P<0.001),
      tumor, node and metastasis (TNM) classification (P=0.002), invasive degree
      (P=0.003) and D-dimer (P=0.013) and fibrinogen concentrations (P=0.042). Tumor
      size (P=0.002), TNM classification (P<0.001) and depth of penetration (P=0.001)
      were independent factors for thrombocytosis. However, thrombocytosis functioned
      as an independent prognostic factor for GC patients with a PLT count >400*109/l
      (relative risk, 1.538; 95% confidence interval, 1.041-2.271). In the majority of
      patients (17/24) with a high preoperative PLT count that decreased to a normal
      level following resection, PLT levels increased again at recurrence.
      Sensitivities and specificities of thrombocytosis for recurrence in those
      patients were 70.8 and 83.3%, respectively (AUROC, 0.847; P=0.01). Therefore, a
      PLT count of 400*109/l is a suitable threshold for defining thrombocytosis in GC.
      Thrombocytosis was shown to affect the blood hypercoagulable state and also have
      a negative prognostic value for GC patients. PLT monitoring following surgery was
      useful to predict the recurrence for specific GC patients that suffered
      preoperative thrombocytosis but had restored PLT levels following resection.

PMID- 24944611
TI  - Possible factors affecting thyroid dysfunction in hepatitis C virus-infected
      untreated patients.
AB  - The present study investigated the association of thyroid dysfunction (TD) with
      the distribution of chronic hepatitis C virus (HCV) infection in untreated
      patients. A total of 1,012 cases of HCV-infected patients were collected from
      different regions, of which 209 patients demonstrated a type of TD (chronic
      thyroiditis complicated with hyperthyroidism, chronic thyroiditis complicated
      with hypothyroidism, subclinical hyperthyroidism, subclinical hypothyroidism,
      hyperthyroidism, hypothyroidism or chronic thyroiditis). The results showed the
      existence of geographical differences in the types of TD present with HCV
      infection. The female patients had a higher incidence of autoimmune-related TD
      than the male patients. High levels of HCV RNA expression were most common in all
      HCV-infected patients, regardless of the presence of TD. High and medium
      expression levels of HCV RNA were more prevalent in the patients with autoimmune
      related TD. Relative analysis of the HCV RNA levels showed that the pathogenesis
      of TD was not correlated with the HCV RNA expression levels; however, it may have
      been associated with autoimmunity. The HCV-infected patients with TD were most
      commonly middle-aged, whereas young adults were the largest group of patients
      with HCV and normal thyroid function. Among all HCV genotypes, type 1b was the
      most common HCV genotype and type 2 was the second most common. Types 3 and 6
      were scarce in this study population. No associations were identified between HCV
      genotypes and thyroid disease. The data of liver function showed that HCV
      infected patients with TD had a higher liver dysfunction rate compared with that
      of the patients with normal thyroid function. Therefore, liver dysfunction may be
      associated with thyroid disease. This study supports the potential of
      individualized treatment for HCV-infected patients.

PMID- 24944612
TI  - Effects of intensive insulin therapy combined with low molecular weight heparin
      anticoagulant therapy on severe pancreatitis.
AB  - The current study explored the effects of intensive insulin therapy (IIT)
      combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe
      acute pancreatitis (SAP). A total of 134 patients with SAP that received
      treatment between June 2008 and June 2012 were divided randomly into groups A
      (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A
      were treated routinely. Group B received continuous pumped insulin, as well as
      the routine treatment, to maintain the blood sugar level between 4.4 and 6.1
      mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition
      to the routine treatment. Group D received IIT + LMWH and the routine treatment.
      The white blood cell count, hemodiastase, serum albumin, arterial partial
      pressure of oxygen and prothrombin time were recorded prior to treatment and 1,
      3, 5, 7 and 14 days after the initiation of treatment. The intestinal function
      recovery time, incidence rate of multiple organ failure (MOF), length of
      hospitalization and fatality rates were observed. IIT + LMWH noticeably increased
      the white blood cell count, hemodiastase level, serum albumin level and the
      arterial partial pressure of oxygen in the patients with SAP (P<0.05). It
      markedly shortened the intestinal recovery time and the length of stay and
      reduced the incidence rate of MOF, the surgery rate and the fatality rate
      (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT +
      LMWH had a noticeably improved clinical curative effect on SAP compared with that
      of the other treatments.

PMID- 24944613
TI  - Insulin glargine effectively achieves glycemic control and improves insulin
      resistance in patients with early type 2 diabetes that exhibit a high risk for
      cardiovascular disease.
AB  - In the present study, the clinical efficacy and safety of administering insulin
      glargine to early type 2 diabetes (T2D) mellitus patients with a high risk for
      cardiovascular disease were assessed. A total of 42 early T2D patients at a high
      risk for cardiovascular disease were randomly divided into an insulin-glargine
      group and a standard-care group. The patients in the insulin-glargine group
      received oral antidiabetic agents plus glargine once a day via a subcutaneous
      injection. The patients in the standard-care group were administered oral
      antidiabetic agents according to the diabetic treatment guidelines. The median
      follow-up period was 6.4 years. Comparisons were made between the two groups with
      regard to levels of plasma glucose, glycosylated hemoglobin (HbA1c) and plasma
      lipids, the homeostasis model assessment-insulin secretion index (HOMA-beta) and
      HOMA-insulin resistance index (HOMA-IR), as well as the incidence of
      hypoglycemia, adverse cardiovascular events and body mass index (BMI). The
      fasting plasma glucose level in the insulin-glargine group was significantly
      lower than that observed in the standard-care group. However, the levels of 2-h
      postprandial glucose, HbA1c and plasma lipids, as well as the BMI, were similar
      when comparing the two groups. Although the level of the HOMA-beta did not differ
      between the two groups, the level of HOMA-IR in the insulin-glargine group was
      significantly lower than that observed in the standard-care group. During the
      follow-up period, the incidence of hypoglycemia in the insulin-glargine group was
      significantly higher when compared with the standard-care group, however, no
      significant difference in the incidence of adverse cardiovascular events was
      observed. Therefore, the results of the present study indicated that insulin
      glargine may effectively achieve glycemic control and improve insulin resistance
      without increasing the risk for cardiovascular events in early T2D patients that
      were considered to be at a high risk for cardiovascular disease.

PMID- 24944614
TI  - JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung
      injury via upregulation of claudin-4.
AB  - Although in vitro studies have previously demonstrated that mitogen-activated
      protein kinases are important for the activation of transcription factors and the
      regulation of proinflammatory mediators, the function of c-Jun NH2-terminal
      kinase (JNK) in acute lung injury (ALI) remains to be fully elucidated. The
      present study aimed to investigate the effect of the JNK selective inhibitor
      SP600125 on lipopolysaccharide (LPS)-induced ALI. Pulmonary edema, the expression
      of inflammatory cytokines and pathological alterations were found to be
      significantly attenuated in LPS-induced ALI following treatment with SP600125 in
      vivo. In vitro, it was demonstrated that SP600125 administration significantly
      improved A549 cell viability in a dose-dependent manner using the Cell Counting
      kit-8 and the 5-ethynyl-2'-deoxyuridine incorporation assay. Furthermore, flow
      cytometric analysis demonstrated that the apoptotic rate was significantly
      reduced in a concentration-dependent manner following SP600125 injection. At the
      molecular level, SP600125 treatment dose-dependently inhibited JNK activation and
      upregulated claudin-4 expression in vivo and in vitro. In combination, the
      results from the present study indicated that the JNK inhibitor SP600125
      protected against LPS-induced ALI in vivo and in vitro, possibly by upregulating
      the expression of claudin-4.

PMID- 24944615
TI  - Monoamine neurotransmitters and fibroblast growth factor-2 in the brains of rats
      with post-stroke depression.
AB  - The aim of the present study was to investigate the changes in the levels of
      serotonin (5-HT), dopamine (DA), norepinephrine (NE) and fibroblast growth factor
      2 (FGF-2) in the brains of rats with post-stroke depression (PSD). A rat model of
      stroke was established by middle cerebral artery occlusion and the rats were
      randomly divided into two groups: Control and modification groups. The rats in
      the modification group had PSD, while the rats in the control group had
      experienced a stroke only. The PSD model was established by applying chronic mild
      stress to the individually housed rats. High-performance liquid chromatography
      was used to detect the levels of 5-HT, DA and NE, while western blotting was used
      to detect the FGF-2 protein expression levels in the frontal lobe and
      hippocampus. Quantitative polymerase chain reaction was also used to determine
      the mRNA expression levels of FGF-2 in the frontal lobes of the two groups. The
      levels of 5-HT, DA and NE in the frontal lobe and hippocampus of the rats in the
      PSD group were significantly lower than the levels observed in the rats in the
      stroke group (P<0.01). In addition, protein expression levels of FGF-2 in the
      frontal lobe of the rats in the PSD group were significantly lower when compared
      with the control group rats (P<0.01), however, the protein expression levels of
      FGF-2 in the hippocampus did not exhibit a statistically significant difference
      (P>0.05). The mRNA expression levels of FGF-2 in the frontal lobe of the rats in
      the modification group were significantly lower than the levels in the control
      group rats (P<0.01). Therefore, reduced levels of monoamine neurotransmitters and
      FGF-2 expression in the brains of rats with PSD are associated with the incidence
      of PSD.

PMID- 24944617
TI  - Effect of ligustilide on Ang II-induced hypertrophy in cardiomyocytes and the
      potential mechanisms.
AB  - The aim of the present study was to investigate the effect of ligustilide (LIG)
      on angiotensin II (Ang II)-induced hypertrophy in neonatal rat myocardial cells
      and the expression levels of p53, Bcl-2 and Bax. Myocardial cells were isolated
      and purified from the ventricles of neonate Sprague-Dawley rats (age, 1-3 days)
      using a differential adhesion method. The cells were then were stimulated by Ang
      II and LIG for 1-3 days, following which the cell surface area, intracellular
      protein concentration, rate of apoptosis and the expression levels of p53, Bcl-2
      and Bax were determined. Following stimulation with Ang II, the cell surface area
      of the neonatal rat myocardial cells increased significantly and the cell
      morphology was distorted. LIG was shown to significantly suppress the Ang II
      induced hypertrophy of neonatal rat myocardial cells in a dose-dependent manner.
      In addition, administration of LIG restored the expression levels of p53, Bcl-2
      and Bax. Therefore, LIG can prevent the hypertrophy of cardiomyocytes induced by
      Ang II, which may be associated with the inhibitory effect that LIG exhibits on
      cardiomyocyte apoptosis.

PMID- 24944616
TI  - Prediction of antiviral efficacy in patients with chronic hepatitis C by changes
      in forkhead box protein 3 levels.
AB  - The aim of the present study was to investigate the distribution of CD4+CD25+
      regulatory T cells (Tregs) in the peripheral blood of patients with chronic
      hepatitis C; in addition to identifying whether the distribution of CD4+CD25+
      Tregs predicts the efficacy of antiviral therapy for HCV. The expression of
      CD4+CD25+ forkhead box protein (FOXP) 3+ Tregs within a CD4+ T cell population
      was detected in the peripheral blood obtained from patients with chronic
      hepatitis C and from healthy control subjects using flow cytometry. The hepatitis
      C virus (HCV)-RNA load was measured using quantitative-fluorescence polymerase
      chain reaction. CD4+CD25+FOXP3+ Tregs accounted for 14.24+/-1.33% of the CD4+ T
      cells in the peripheral blood of patients with chronic hepatitis C, which was
      higher than that of the healthy control subjects (5.62+/-1.21%; P<0.001).
      Furthermore, the frequency of CD4+CD25+FOXP3+ Tregs in CD4+ T cells of the
      peripheral blood positively correlated with the HCV-RNA load (r=0.73; P=0.032).
      Therefore, the results of the present study indicated that the expression of
      CD4+CD25+FOXP3+ Tregs increased in patients that were chronically infected with
      HCV and positively correlated with the HCV-RNA load.

PMID- 24944618
TI  - Detection of serum VEGF and MMP-9 levels by Luminex multiplexed assays in
      patients with breast infiltrative ductal carcinoma.
AB  - The aim of the present study was to assess the effect of the combined detection
      of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9
      (MMP-9) by Luminex multiplexed assays for the diagnosis, treatment and prognosis
      of breast cancer. Preoperative levels of serum VEGF and MMP-9 were detected via a
      lipid chip-based method in 301 breast cancer cases, 83 breast fibroadenoma cases
      and 40 healthy adults. Postoperative levels of VEGF and MMP-9 were also detected
      in 118 breast cancer cases. The levels of serum VEGF and MMP-9 in patients with
      breast infiltrative ductal carcinoma (IDC) were higher than those in the breast
      fibroadenoma and healthy control groups (P<0.05); there was no statistically
      significant difference between the breast fibroadenoma and healthy groups
      (P>0.05). The levels of VEGF and MMP-9 were shown to correlate with the clinical
      stage, tumor size and the lymph node metastasis status. However, the levels were
      not associated with age or gender (P>0.05). In addition, the serum level of MMP-9
      exhibited a significantly correlation with the VEGF level (r=0.601, P<0.001).
      Subgroup analysis revealed that in patients with IDC, serum levels of VEGF and
      MMP-9 prior to surgery were significantly higher than those following surgery
      (P<0.05). Therefore, the serum levels of VEGF and MMP-9 can be used as markers
      for the diagnosis of breast IDC and may also be valuable for the prediction of
      lymph nodes metastasis.

PMID- 24944619
TI  - Association between inflammatory biomarkers and adiposity in obese patients with
      heart failure and metabolic syndrome.
AB  - Obesity, type 2 diabetes mellitus (DM) and metabolic syndrome (MS) are common in
      patients with heart failure (HF). Studies investigating the association between
      known biomarkers and adiposity in patient populations are limited. The aim of the
      present study was to investigate the association between C-reactive protein (CRP)
      and leptin with adiposity in a sub-group of overweight/obese patients with HF, DM
      and/or MS. A total of 36 patients (mean age, 56.72+/-9.78 years; ranging between
      27 and 76 years of age; 80.6% male; 52.8% Caucasian) were enrolled and their
      height, weight, waist circumference and body composition (e.g. percentage body
      fat and lean mass), as well as the levels of CRP and leptin, were assessed. The
      results demonstrated that there was a significant association between CRP and
      leptin, CRP and body mass index (BMI) and gender and percentage body fat (P<0.05,
      for all associations). Analysis of leptin and CRP levels revealed that patients
      in the highest BMI quartile (BMI, 40.3-61.2) had higher CRP levels (4.83 MUg/ml
      vs. 3.03 MUg/ml; P=0.033) and higher leptin levels (44.97 ng/ml vs. 24.64 ng/ml;
      P=0.042) compared with patients in the lower BMI quartile (BMI, 28.6-32.4). In
      conclusion, among obese patients with HF, DM and/or MS, an association between
      CRP and leptin was identified, providing further evidence that metabolic and
      inflammatory mechanisms are involved in these diseases. Future investigation to
      assess the potential impact of inflammation and adiposity, and the role of
      dietary interventions and weight loss on clinical outcomes in this population of
      chronically ill patients is warranted.

PMID- 24944620
TI  - Effect of pretreatment with transdermal testosterone on poor ovarian responders
      undergoing IVF/ICSI: A meta-analysis.
AB  - In order to identify and describe the effectiveness of transdermal testosterone
      pretreatment on poor ovarian responders, MEDLINE, EMBASE, the Cochrane library
      and the Chinese biomedical database were searched for randomized controlled
      trials (RCTs). Three RCTs, which compared the outcomes of female pretreatment
      with transdermal testosterone prior to in vitro fertilization/intracytoplasmic
      sperm injection (IVF/ICSI) with those of control groups, were included in the
      present review. The three RCTs enrolled a total of 221 randomized subjects. The
      meta-analysis revealed that females who received transdermal testosterone
      treatment prior to their IVF/ICSI cycle had a two-fold increase in live birth
      rate [risk ratio (RR)=2.01, 95% confidence interval (CI) 1.03-3.91], clinical
      pregnancy rate (RR=2.09, 95% CI 1.14-3.81) and a significantly more oocyte
      retrieved [mean difference (MD)=1.36, 95% CI 0.82-1.90]. The current findings
      provide evidence that pretreatment with transdermal testosterone may improve the
      clinical outcomes for poor ovarian responders undergoing IVF/ICSI. However, the
      results should be interpreted with caution due to the small sample size of the
      studies used and the heterogeneities. Further good quality RCTs would be needed
      to reach further conclusions.

PMID- 24944621
TI  - Altered glutamate cysteine ligase activity in peripheral blood mononuclear cells
      from patients with systemic lupus erythematosus.
AB  - Reductions in glutathione (GSH) levels have been shown to be associated with
      aging and the pathogenesis of a variety of diseases, including systemic lupus
      erythematosus (SLE). Glutamate cysteine ligase (GCL) catalyzes the first and rate
      limiting step of GSH synthesis. In order to appraise the correlation between
      oxidative stress and the severity and activity of SLE, GSH, oxidized GSH (GSSG)
      and thioredoxin (TRX) concentrations and the enzymatic activity levels of GCL in
      peripheral blood mononuclear cells (PBMCs) from patients with SLE and healthy
      controls were studied. In patients with SLE, the levels of GCL activity and GSH
      decreased, while TRX and GSSG levels increased when compared with those in the
      healthy controls. GSH concentrations and GCL activity levels negatively
      correlated with the SLE disease activity index and erythrocyte sedimentation
      rate. Furthermore, patients with SLE and nephritis had lower levels of GSH and
      GCL activity and higher levels of TRX and GSSG compared with those in SLE
      patients without nephritis. Therefore, the results of the present study indicate
      that insufficient levels of GSH and GCL activity in PBMCs may contribute to the
      pathogenesis of SLE.

PMID- 24944622
TI  - Feasibility and efficacy of a remote real-time wireless ECG monitoring and
      stimulation system for management of ventricular arrhythmia in rabbits with
      myocardial infarction.
AB  - The purpose of this study was to explore the feasibility of continuous remote
      monitoring, and the induction and termination of malignant ventricular
      arrhythmias (VAs) by a novel implantable electronic cardiovascular device (IECD)
      system in rabbits with myocardial infarction (MI). The IECD was implanted and MI
      was induced by ligation of the left anterior descending coronary artery in 20
      adult rabbits. Internet-based remote electrocardiogram (ECG) monitoring and
      ventricular stimulation were conducted in remote locations with internet access.
      The voltage amplitudes of the stimulation signals were recorded synchronously by
      remote and surface ECG. Programmed stimulation with regular stimuli and regular
      stimuli with an added extra stimulus were performed prior to and following the MI
      surgery to induce and terminate VAs. IECD implantation and MI surgery, as well as
      qualified remote and bidirectional signal communications between the implanted
      IECD and extracorporeal system, were successfully achieved in 18 rabbits. The
      voltage of the stimulation signals recorded by the remote and surface ECGs showed
      a good correlation with the stimulation current (remote ECG, r=0.972 and surface
      ECG, r=0.988; P<0.001). Sustained ventricular tachycardia (VT) was induced in
      five rabbits (5/20, 25%) prior to MI induction and in 12 rabbits (12/16, 75%)
      following MI induction. Of the 17 induced VTs, 16 were successfully terminated by
      remote ventricular stimulation. The novel IECD system provides qualified remote
      wireless ECG monitoring and possesses the potential to induce and terminate VAs
      by remote ventricular pacing in this rabbit model of MI. Thus, this model of MI
      may be used to test the efficacy of novel drugs and devices for the management of
      VAs.

PMID- 24944623
TI  - Indole-3-carbinol inhibits nasopharyngeal carcinoma cell growth in vivo and in
      vitro through inhibition of the PI3K/Akt pathway.
AB  - Indole-3-carbinol (I3C) is an active component of cruciferous vegetables and has
      been shown to markedly inhibit the growth of a variety of tumors. However, the
      role of I3C in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the aim of
      the present study was to investigate the inhibition of NPC cells by I3C in vitro
      and in vivo. The human CNE2 NPC cell line was treated with various concentrations
      (0, 100, 200 and 300 MUM) of I3C and analysis of cell proliferation after 0, 24,
      48 and 72 h, apoptosis after 48 h and expression levels of phosphatidylinositol 3
      kinase (PI3K)/Akt pathway-associated proteins in vitro was performed. BALB/c nude
      mice were divided into the following groups: Prevention, treatment and control.
      In vivo, all the nude mice were inoculated with CNE2 NPC cells and the mice in
      the prevention and treatment groups were administered a diet containing 0.5% I3C
      prior to and following inoculation, respectively. The tumoricidal effect of I3C
      was investigated in the nude mice. After eight weeks, the expression levels of
      PI3K/Akt pathway-associated proteins were analyzed in the tumors from the nude
      mice in each group. The results demonstrated that with increasing I3C
      concentrations, cell proliferation decreased and apoptosis increased
      significantly. In addition, the expression levels of PI3K/Akt pathway-associated
      proteins decreased. In the animal experiments, the prevention and treatment
      groups developed smaller tumors and the expression levels of PI3K/Akt pathway
      associated proteins were reduced when compared with those in the control group.
      In addition, very few changes to the heart, liver and kidney tissues were
      observed with hematoxylin and eosin staining in all the groups. Therefore, the
      results of the present study indicated that I3C inhibited the growth of NPC cells
      and induced apoptosis effectively in vivo and in vitro. The underlying mechanism
      may be that I3C suppresses the PI3K/Akt pathway.

PMID- 24944624
TI  - Association between IL-21 gene rs907715 polymorphisms and Graves' disease in a
      Southern Chinese population.
AB  - Interleukin-21 (IL-21) is a pleiotropic cytokine linking innate and adaptive
      immune responses, which has been reported to play a key role in multiple
      autoimmune diseases. The aim of the present case-control study was to investigate
      the genetic association between single nucleotide polymorphisms (SNPs) of
      rs907715 within the IL-21 gene and Graves' disease (GD) in a Southern Chinese
      population. A total of 211 patients with GD and 212 control subjects were
      recruited for the study. IL-21 gene rs907715 polymorphisms were detected by
      direct DNA sequencing. The results indicated that the frequencies of the GG
      genotype and the G allele in GD patients were significantly increased when
      compared with the frequencies in the controls (P=6.7*10-3 and P=2.0*10-5,
      respectively). In addition, the frequency of the AA genotype was much lower in
      the patient group when compared with the control group (16.6 vs. 34.0%; P=4.0*10
      5). Furthermore, the G allele of rs907715 was associated with relapse in GD
      patients. These observations indicated that polymorphisms of IL-21/rs907715 may
      affect the susceptibility to GD in a Southern Chinese population. The G allele
      was significantly associated with an increased risk of GD development, whereas
      the A allele may lower the susceptibility to GD.

PMID- 24944625
TI  - Atorvastatin increases lipopolysaccharide-induced expression of tumour necrosis
      factor-alpha-induced protein 8-like 2 in RAW264.7 cells.
AB  - RAW264.7 cells are one of the major sources of productive inflammatory
      biomediators, including tumour necrosis factor-alpha (TNF-alpha) and interleukin
      (IL)-6. TNF-alpha-induced protein 8-like 2 (TIPE2) is an essential negative
      regulator of Toll-like and T-cell receptors, and the selective expression in the
      immune system prevents hyper-responsiveness and maintains immune homeostasis. The
      aim of the present study was to investigate whether atorvastatin upregulates the
      expression of TIPE2 and further regulates the inflammatory response and oxidation
      emergency response in RAW264.7 cells. RAW264.7 cells were incubated in Dulbecco's
      modified Eagle's medium containing lipopolysaccharide (LPS) in the presence or
      absence of atorvastatin. Following incubation, the medium was collected and the
      levels of TNF-alpha and IL-6 were measured using an enzyme-linked immunosorbent
      assay. The cells were harvested, and the mRNA and protein expression levels of
      TIPE2, macrophage migration inhibitory factor (MIF), IkappaB and nuclear factor
      (NF-kappaB)-kappaB were analysed using quantitative polymerase chain reaction and
      western blotting analysis, respectively, the expression of NOS, COX-2 and HO-1
      protein were essayed by western blotting analysis, NO and ROS activities were
      determined. The results revealed that LPS increased the mRNA and protein
      expression levels of TIPE2, MIF and NF-kappaB, as well as the production of IL-6
      and TNF-alpha, in a dose and time dependent manner in RAW264.7 cells. Meanwhile,
      LPS enhanced the expression of NOS and COX-2 protein, blocked HO-1 protein
      expression, increased NO and PGE2 production and ROS activity in a dose dependent
      manner in RAW264.7 cells. Atorvastatin significantly increased LPS induced
      expression of TIPE2, downregulated the expression of NOS, COX-2, MIF and NF
      kappaB and the production of PGE2, NO, IL-6 and TNF-alpha in a time and dose
      dependent manner, and increased HO-1 protein expression, reduced ROS production
      in a dose dependent manner. The observations indicated that atorvastatin
      upregulated LPS induced expression of TIPE2 and consequently inhibited MIF, NF
      kappaB, NOS and COX-2 expression and the production of NO, PGE2, TNF-alpha and IL
      6, increased HO-1 expression, and inhibited ROS activity in cultured RAW264.7
      cells.

PMID- 24944626
TI  - Anti-inflammatory effect of sodium butyrate preconditioning during myocardial
      ischemia/reperfusion.
AB  - High mobility group box 1 protein (HMGB1) has an important role in myocardial
      ischemia/reperfusion (I/R) injury. Sodium butyrate, an inhibitor of histone
      deacetylase, has been shown to inhibit HMGB1 expression. In the present study,
      the effect of sodium butyrate on myocardial I/R injury in rats was investigated.
      Anesthetized male rats were intraperitoneally administered sodium butyrate (100
      or 300 mg/kg) 30 min prior to the induction of ischemia. The rats were then
      subjected to ischemia for 30 min followed by reperfusion for 4 h. Infarct size,
      lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD)
      activity and malondialdehyde (MDA) levels were then measured. The expression of
      HMGB1 was assessed using western blot analysis. The results demonstrated that
      pretreatment with sodium butyrate (300 mg/kg) significantly reduced the infarct
      size, as well as the levels of LDH and CK (P<0.05). In addition, sodium butyrate
      (300 mg/kg) was shown to significantly inhibit the I/R-induced increase in the
      level of MDA and reduction in the level of SOD (P<0.05). Furthermore, treatment
      with sodium butyrate (300 mg/kg) was found to significantly inhibit the
      expression of TNF-alpha, IL-6 and HMGB1 induced by I/R injury (P<0.05). In
      conclusion, the results from the present study suggest that preconditioning with
      sodium butyrate may attenuate myocardial I/R injury by inhibition of the
      expression of inflammatory mediators during myocardial I/R.

PMID- 24944627
TI  - A case report of acute severe paraquat poisoning and long-term follow-up.
AB  - In the present study, the successful management of severe paraquat (PQ) poisoning
      with multiple organ dysfunction syndrome is described. A 42-year-old female
      ingested >100 ml PQ (20% weight/volume) in an attempted suicide. After 22 h the
      patient was admitted to hospital with serious liver, kidney and lung damage.
      Comprehensive therapy that maximized poison elimination was administered, along
      with appropriate glucocorticoids and medication for anticoagulation and
      protection of the liver and kidney. The patient was successfully treated and
      recovered after 40 days. However, pulmonary damage was aggravated when the
      glucocorticoid treatment was stopped after 2 months; the lungs recovered again
      following systematic therapy. Subsequent to a 8-month follow-up, the patient was
      able to look after herself in her daily life. To the best of our knowledge,
      successful treatment following severe PQ poisoning is rare.

PMID- 24944628
TI  - CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive
      memory T cells in a mouse retransplantation model.
AB  - C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 play key roles in the initiation
      and development of acute transplant rejection. Previously, higher levels of
      RANTES expression and secretion were demonstrated in retransplantation or T-cell
      memory-transfer models. In the present study, the effect of the chemokines, CXCL9
      and CXCL10, were investigated in a mouse retransplantation model. BALB/c mice
      were used as donors, while C57BL/6 mice were used as recipients. In the
      experimental groups, a heterotopic heart transplantation was performed six weeks
      following skin grafting. In the control groups, a heterotopic heart
      transplantation was performed without skin grafting. Untreated mice served as
      blank controls. The mean graft survival time of the heterotopic heart
      transplantations was 7.7 days in the experimental group (n=6), as compared with
      3.25 days in the control group (n=6; P<0.001). On day three following cardiac
      transplantation, histological evaluation of the grafts revealed a higher
      International Society for Heart & Lung Transplantation grade in the experimental
      group as compared with the control group. In addition, gene expression and serum
      concentrations of CXCL9, CXCL10, interferon-gamma, and interleukin-2 were
      markedly higher in the experimental group when compared with the control group.
      Differences between the levels of CXCL9 and CXCL10 in the pre- and post
      transplant mice indicated that the chemokines may serve as possible biomarkers to
      predict acute rejection. The results of the present study demonstrated that CXCL9
      and CXCL10 play a critical role in transplantation and retransplantation. High
      levels of these cytokines during the pre-transplant period may lead to extensive
      acute rejection. Thus, the observations enhance the understanding of the
      mechanism underlying the increased expression and secretion of CXCL9 and CXCL10
      by alloreactive memory T cells.

PMID- 24944629
TI  - Effect of initial temperature changes on myocardial enzyme levels and cardiac
      function in acute myocardial infarction.
AB  - In the present study, the effect of initial body temperature changes on
      myocardial enzyme levels and cardiac function in acute myocardial infarction
      (AMI) patients was investigated. A total of 315 AMI patients were enrolled and
      the mean temperature was calculated based on their body temperature within 24 h
      of admission to hospital. The patients were divided into four groups according to
      their normal body temperature: Group A, <36.5 degrees C; group B, >=36.5 degrees
      C and <37.0 degrees C; group C, >=37.0 degrees C and <37.5 degrees C and group D,
      >=37.5 degrees C. The levels of percutaneous coronary intervention, myocardial
      enzymes and troponin T (TNT), as well as cardiac ultrasound images, were
      analyzed. Statistically significant differences in the quantity of creatine
      kinase at 12 and 24 h following admission were identified between group A and
      groups C and D (P<0.01). A significant difference in TNT at 12 h following
      admission was observed between groups A and D (P<0.05), however, this difference
      was not observed with groups B and C. The difference in TNT between the groups at
      24 h following admission was not statistically significant (P>0.05). Significant
      differences in lactate dehydrogenase at 12 and 24 h following admission were
      observed between groups A and D (P<0.05), however, differences were not observed
      with groups B and C (P>0.05). Significant differences in glutamic-oxaloacetic
      transaminase at 12 and 24 h following admission were observed between groups A
      and D (P<0.05), however, differences were not observed in groups B and C
      (P>0.05). However, no significant differences were identified in cardiac function
      index between all the groups. Therefore, the results of the present study
      indicated that AMI patients with low initial body temperatures exhibited
      decreased levels of myocardial enzymes and TNT. Thus, the observation of an
      initially low body temperature may be used as a protective factor for AMI and may
      improve the existing clinical program.

PMID- 24944630
TI  - Rhizoma Pinelliae trypsin inhibitor separation, purification and inhibitory
      activity on the proliferation of BGC-823 gastric adenocarcinoma cells.
AB  - The aim of this study was to isolate and purify Rhizoma Pinelliae trypsin
      inhibitor (RPTI), determine its N-terminal amino acid sequence and evaluate its
      inhibitory effect on the proliferation of poorly differentiated BGC-823 human
      gastric adenocarcinoma cells. RPTI was separated and purified from a 40%
      (NH4)2SO4 precipitate of crude protein extract of Pinellia ternata tuber using
      affinity chromatography with trypsin as the ligand. The N-terminal amino acid
      sequence of RPTI was determined using the Edman degradation method. The
      inhibitory effect of RPTI on BGC-823 cell proliferation was detected in vitro
      using the MTT method and in vivo in tumour-bearing mice. The purified RPTI showed
      a single band under SDS-PAGE, its molecular weight was 14 kDa and its N-terminal
      amino acid sequence was DPVVDG. RPTI inhibited trypsin activity, with an
      inhibition ratio of 1:6.78 (mass). RPTI significantly inhibited the proliferation
      of BGC-823 cells in vitro. The IC50 of RPTI was 16.96 MUg/ml within 48 h after
      treatment and 9.61 MUg/ml within 72 h after treatment. Subcutaneous injection of
      RPTI around the tumour significantly inhibited BGC-823 tumour growth in mice. The
      tumour inhibitory effect was concentration- and dose-dependent. RPTI did not
      significantly influence the spleen coefficient of the mice. In conclusion, RPTI
      is a serine proteinase inhibitor with antitumour activity.

PMID- 24944631
TI  - Correlation between sialic acid levels in the synovial fluid and the radiographic
      severity of knee osteoarthritis.
AB  - Osteoarthritis (OA) is associated with the presence of inflammation. Sialic acid
      (SA), an acetylated derivative of neuraminic acid, is reported to be a useful
      biomarker of inflammation. The aim of the present study was to investigate the
      correlation between SA levels in the serum and synovial fluid (SF) and
      radiographic severity in patients with knee OA. A total of 234 patients with knee
      OA were recruited for the study, as well as 20 patients that had suffered a knee
      injury or fracture (without knee OA) and 160 healthy controls. Radiological
      grading of OA in the knee was conducted according to the Kellgren-Lawrence (KL)
      grading system. SA levels in the serum and SF were measured using Warren's
      thiobarbituric acid assay. The results demonstrated that knee OA patients
      exhibited significantly elevated levels of serum SA when compared with the
      healthy controls, and also significantly elevated levels of SF SA when compared
      with the knee fracture patients. Higher SA levels in the SF were identified in
      knee OA patients with KL grade 4 as compared with patients with KL grade 2 or 3.
      In addition, OA patients of KL grade 3 had significantly higher SA levels in the
      SF as compared with patients with KL grade 2 (P<0.01). The SA levels in the SF of
      the knee OA patients positively correlated with the KL grades (r=0.353; P<0.01).
      However, there was no significant correlation identified between serum SA levels
      and KL grade. Therefore, SA levels in the SF positively correlated with the
      radiographic severity of OA, thus, SA levels in the SF may serve as a biomarker
      for the progression of OA.

PMID- 24944632
TI  - Piperine potentiates the hypocholesterolemic effect of curcumin in rats fed on a
      high fat diet.
AB  - It has previously been demonstrated that curcumin possesses a hypocholesterolemic
      effect and potentiates numerous pharmacological effects of curcumin, however, the
      mechanisms underlying this hypocholesterolemic effect and the interaction between
      curcumin and piperine remain to be elucidated. In the present study, male Sprague
      Dawley rats were fed on a high-fat diet (HFD) to establish a hyperlipidemia (HLP)
      model. Co-administration of curcumin plus piperine was found to decrease the
      levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein
      cholesterol in the serum and liver, as well as increase the levels of fecal TC,
      TG and total bile acid, compared with administration of curcumin alone. Curcumin
      plus piperine also markedly increased the levels of high-density lipoprotein
      cholesterol. Furthermore, compared with administration of curcumin alone,
      administration of curcumin plus piperine resulted in a significant upregulation
      of the activity and gene expression of apolipoprotein AI (ApoAI), lecithin
      cholesterol acyltransferase (LCAT), cholesterol 7alpha-hydroxylase (CYP7A1) and
      low-density lipoprotein receptor (LDLR). In conclusion, these results indicated
      that co-administration of curcumin plus piperine potentiates the
      hypocholesterolemic effects of curcumin by increasing the activity and gene
      expression of ApoAI, CYP7A1, LCAT and LDLR, providing a promising combination for
      the treatment of HLP.

PMID- 24944633
TI  - Interferon-alpha enhances the susceptibility of renal cell carcinoma to rapamycin
      by suppressing mTOR activity.
AB  - The aim of the present study was to investigate the antiproliferative effects of
      interferon (IFN)-alpha and rapamycin (RPM) on renal cell carcinoma (RCC) cells
      and examine the synergistic growth suppression conferred by IFN-alpha and RPM.
      The effects of IFN-alpha and/or RPM on RCC cells were determined using a WST-1
      assay and the synergy of IFN-alpha and RPM against three RCC cell lines was
      analyzed with isobolographic analysis. The expression of mammalian target of
      rapamycin (mTOR) was downregulated by RNAi, and the expression and
      phosphorylation of proteins in the mTOR pathway following treatment with IFN
      alpha and/or RPM was examined by western blot analysis. The observations
      indicated that IFN-alpha significantly increased the susceptibility of RCC cells
      to RPM and the synergistic effect of IFN-alpha and RPM against RCC cells was
      confirmed in all three RCC cell lines. The mTOR pathway was shown to be
      associated with the synergistic effect of IFN-alpha and RPM against RCC. IFN
      alpha and RPM alone decreased the phosphorylation of mTOR, p70 S6 kinase, S6 and
      4E binding protein 1, and IFN-alpha significantly enhanced the RPM-induced
      suppression of the mTOR pathway. However, in RCC cells with low mTOR activity,
      the synergy of IFN-alpha and RPM was eliminated. Therefore, the results of the
      present study indicate that the mTOR pathway plays an important role in the
      synergistic effect of IFN-alpha and RPM against RCC cells. Thus, mTOR may serve
      as an effective therapeutic target in the treatment of advanced RCC.

PMID- 24944634
TI  - In vivo determination of muscle-derived stem cells in the rat corpus cavernosum.
AB  - The aim of the present in vivo study was to determine the presence of muscle
      derived stem cells (MDSCs) in the corpus cavernosum of rats. Immunohistochemistry
      and reverse transcription polymerase chain reaction (RT-PCR) were performed to
      detect the expression of the stem cell markers stem cell antigen-1 (Sca-1), Oct4
      and Desmin in Sprague-Dawley rats aged 2, 5 and 20 months. Sca-1 was mainly
      expressed in the blood vessels and cavernous sinus and staining revealed that Sca
      1 was predominantly expressed in the cytoplasm. Desmin was primarily expressed in
      muscular tissues and staining demonstrated that it was mainly expressed in the
      cytoplasm, however, Desmin was also partially expressed in the nuclei. A small
      number of double positive cells, expressing Sca-1 and Desmin, were also detected
      near the cavernous sinus. It was found that the expression of the markers was
      negatively correlated with the age of the rats (P<0.05). The results from the RT
      PCR demonstrated that the expression levels of Sca-1 and Desmin significantly
      decreased with age (P<0.05). In addition, the correlation analysis indicated that
      the expression of Sca-1 and Desmin were negatively correlated with the age of the
      rats (r=--0.929; P<0.05). In conclusion, the present study provided evidence for
      the presence of MDSCs in the rat corpus cavernosum. MDSCs may be a potential
      therapeutic treatment for organic erectile dysfunction.

PMID- 24944635
TI  - Hypoglycemic and anti-depressant effects of Zuogui Jiangtang Jieyu formulation in
      a model of unpredictable chronic mild stress in rats with diabetes mellitus.
AB  - This study aimed to investigate the hypoglycemic, lipid-lowering and
      antidepressant effects of Zuogui Jiangtang Jieyu formulation (ZGJTJY) in a model
      of unpredictable chronic mild stress (UCMS) in rats with diabetes mellitus (DM;
      the UCMS-DM model). Sixty rats were randomly divided into blank control, vehicle
      (model plus vehicle), positive control (model plus metformin and fluoxetine), and
      high, medium and low dose ZGJTJY (model plus high, medium and low doses of
      ZGJTJY, respectively) groups. Following establishment of DM by a high-fat diet
      with intraperitoneal injection of streptozotocin (38 mg/kg), the depression model
      was established by application of UCMS for 28 days. The behavioral scores of the
      rats were detected in an open field test and Morris water maze test. The levels
      of blood glucose, glycosylated hemoglobin (HbA1c) and blood lipids were assayed.
      The total scores of the open field test and the space exploration times (SETs) in
      the Morris water maze test were significantly lower and the escape latency (EL)
      times in the Morris water maze test were significantly longer in the vehicle
      group compared with those in the blank control group. In addition, in the vehicle
      group, the levels of blood glucose, HbA1c, total cholesterol (TC), triglycerides
      (TGs) and low-density lipoprotein cholesterol (LDL-C) were significantly higher
      and the levels of high-density lipoprotein cholesterol (HDL-C) were significantly
      lower compared with those in the blank control group. The high dose of ZGJTJY
      decreased the locomotor activity levels in the open field test, the EL times of
      the model on day 4, the SETs in the Morris water maze test and the HDL-C levels,
      and reduced the blood glucose, HbA1c, TC, TG and LDL-C levels compared with those
      in the model group. Thus, ZGJTJY is a potential candidate for the prevention and
      treatment of the comorbidity of depression with DM.

PMID- 24944636
TI  - T313M polymorphism of the PINK1 gene in Parkinson's disease.
AB  - The present study aimed to investigate the association between T313M polymorphism
      at exon 4 of the PTEN-induced putative kinase 1 (PINK1) gene and Parkinson's
      disease (PD) in the Uygur and Han populations of Xinjiang, China. Genetic DNA was
      extracted from 364 patients with PD from the Uygur and Han populations, as well
      as 346 normal control patients. Four exons of the PINK1 gene were amplified using
      quantitative polymerase chain reaction. The exons were then digested for
      restriction fragment length polymorphism analysis. Gene types and allele
      frequencies were identified using agarose gel electrophoresis followed by DNA
      sequencing to analyze the T313M polymorphisms. In the Han population, T313M
      polymorphism allele frequency was observed to be significantly different between
      the PD group and the control group (chi2=6.247; P<0.05). Significant differences
      were observed in in the T313M allele and genotype frequencies between the Uygur
      and Han populations (chi2=5.475 and chi2=10.950, respectively; P<0.05).
      Polymorphisms in the PINK1 T313M mutation may be associated with genetic
      susceptibility to PD.

PMID- 24944637
TI  - Effect of bevacizumab combined with boron neutron capture therapy on local tumor
      response and lung metastasis.
AB  - The aim of the present study was to evaluate the effect of bevacizumab on local
      tumor response and lung metastatic potential during boron neutron capture therapy
      (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6
      melanoma tumor-bearing C57BL/6 mice were continuously administered
      bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors
      were irradiated with thermal neutron beams following the administration of a 10B
      carrier [L-para-boronophenylalanine-10B (BPA) or sodium
      mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of
      bevacizumab. This was further combined with an acute hypoxia-releasing agent
      (nicotinamide) or mild temperature hyperthermia (MTH, 40 degrees C for 60 min).
      Immediately following the irradiation, cells from certain tumors were isolated
      and incubated with a cytokinesis blocker. The responses of the Q cells and the
      total (P+Q) cell populations were assessed based on the frequency of micronuclei
      using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days
      following irradiation, lung metastases were enumerated. Three days following
      bevacizumab administration, the sensitivity of the total tumor cell population
      following BPA-BNCT had increased more than that following BSH-BNCT. The
      combination with MTH, but not with nicotinamide, further enhanced total tumor
      cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH
      enhanced the sensitivity of the Q cell population. Regardless of irradiation, the
      administration of bevacizumab, as well as nicotinamide treatment, demonstrated
      certain potential in reducing the number of lung metastases especially in BPA
      BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined
      with bevacizumab has the potential to sensitize total tumor cells and cause a
      reduction in the number of lung metastases to a similar level as nicotinamide.

PMID- 24944638
TI  - Expression of circulating vascular endothelial growth factor-antagonizing
      cytokines and vascular stabilizing factors prior to and following bypass surgery
      in patients with moyamoya disease.
AB  - The aim of the present study was to investigate the levels of vascular
      endothelial growth factor (VEGF)-antagonizing cytokines and VEGF-influenced
      vascular stabilizing cytokines in patients with moyamoya disease (MMD) and the
      association with postoperative collateral vessel formation. The study population
      included 53 MMD patients that had undergone indirect bypass surgery and 50
      healthy controls. Serum levels of VEGF, thrombospondin-1 (TSP-1), TSP-2, soluble
      VEGF receptor-1 (sVEGFR-1), sVEGFR-2, endostatin, angiopoietin-1 (Ang-1) and Ang
      2 were measured at the baseline (preoperative) and at day seven following
      surgery. Postoperative collateralization assessment was conducted upon the six
      month follow-up cerebral angiography. Cytokine levels were compared between
      patients with good or poor collateral formation. Compared with the healthy
      controls, MMD patients exhibited lower baseline levels of sVEGFR-1 (P<0.0001) and
      sVEGFR-2 (P<0.0001), but higher VEGF expression (P<0.0001). Ang-1 and Ang-2
      levels did not exhibit any difference between the two groups. On day seven
      following surgery, MMD patients exhibited an almost unchanged sVEGFR-1 and sVEGFR
      2 expression level, but upregulated expression of VEGF (P<0.0001), Ang-1
      (P<0.0001) and TSP-2 (P<0.0001). The six-month follow-up angiographies revealed
      that 21 patients (45.65%) that had undergone the same surgical procedure achieved
      good collateralization. Patients with good collateral formation appeared to have
      lower sVEGFR-1 and sVEGFR-2 levels prior to (P=0.029 and P=0.045, respectively)
      and at day seven (P=0.044 and P=0.047, respectively) following bypass surgery
      when compared with the patients with worse collateralization. Therefore, sVEGFR-1
      and sVEGFR-2 may play a role in the pathogenesis of MMD. Lower levels of sVEGFR-1
      and sVEGFR-2 indicated better postoperative collateralization in the six months
      following indirect bypass surgery. However, Ang-1 and Ang-2 may not be
      specifically involved in the course of MMD.

PMID- 24944639
TI  - MicroRNA-203 inhibits malignant melanoma cell migration by targeting versican.
AB  - MicroRNA (miR)-203 has been demonstrated to function as a suppressor in
      tumorigenesis. Recently, miR-203 was reported to play a role in malignant
      melanoma (MM); however, the detailed function of miR-203 in MM remains unclear.
      In the present study, the expression of miR-203 was shown to be significantly
      downregulated in MM tissues when compared with normal adjacent tissues. Based on
      a bioinformatic prediction, versican was further identified as a novel target of
      miR-203, and the expression of versican was markedly increased in MM tissues.
      Inhibition of miR-203 increased the protein expression of versican, while
      upregulation of miR-203 inhibited the protein expression of versican in MM A375
      cells. In addition, the upregulation of versican significantly promoted A375 cell
      migration; however, upregulation of miR-203 suppressed A375 cell migration. The
      present study further investigated whether miR-203 was involved in versican
      mediated A375 cell migration, and the results indicated that upregulation of miR
      203 significantly inhibited A375 cell migration, which was impaired by
      overexpression of versican. These observations indicated that versican functions
      as a downstream effector in miR-203-mediated MM cell migration. Therefore, the
      results demonstrated that miR-203 exhibited an inhibitory effect on MM cell
      migration via directly targeting versican, thus, may become an effective
      inhibitor for MM metastasis.

PMID- 24944640
TI  - Preventive effect of polysaccharides from the large yellow croaker swim bladder
      on HCl/ethanol induced gastric injury in mice.
AB  - In the present study the preventive effect of polysaccharides from the large
      yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR
      mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the
      levels of the serum proinflammatory cytokines interleukin (IL)-1beta, IL-6, IL-8,
      as well as increase the levels of IL-4 compared with those in mice treated with a
      low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive
      intestinal peptide serum levels in PLYCSB-treated mice were higher compared with
      those in control mice, whilst motilin and substance P serum levels were lower
      compared with those in control mice. The extent of the gastric injury in the mice
      treated with PLYCSB was lower compared with that in the control mice; however,
      the results obtained for mice treated with a high dose of PLYCSB were similar to
      those for omeprazole-treated mice. In addition, the superoxide dismutase and
      glutathione peroxidase activities of PLYCSB-treated mice were higher compared
      with those of the control mice, and similar to those observed in normal and
      omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric
      oxide and malondialdehyde that were similar to those in the normal group. Using
      PCR and western blot analysis, it was demonstrated that PLYCSB significantly
      inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury
      mice by downregulating the expression of inducible nitric oxide synthase,
      cyclooxygenase-2, tumor necrosis factor-alpha and IL-1beta. These results suggest
      that PLYCSB has an inhibitory effect against gastric injury that is comparable to
      that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential
      to be used as a natural therapeutic drug.

PMID- 24944641
TI  - Clinical improvement following therapy for periodontitis: Association with a
      decrease in IL-1 and IL-6.
AB  - Although a number of inflammatory cytokines have been shown to be associated with
      periodontal pathogenesis, it is important to investigate further whether these
      biomarkers are associated with the degree of success in nonsurgical treatment of
      chronic periodontitis. The aim of the present study was to quantify the total
      levels of interleukin (IL)-1alpha, -1beta, -6, -10 and tumour necrosis factor
      (TNF)-alpha in gingival crevicular fluid (GCF) of chronic periodontitis patients
      prior to and following nonsurgical periodontal therapy. In total, 52 GCF samples
      from disease sites of patients with chronic periodontitis, prior to and following
      periodontal therapy, and ten non-disease sites from non-periodontitis subjects,
      were collected and cytokine concentrations were determined using a multiplex
      method. Periodontal parameters, including bleeding on probing, probing pocket
      depth and the clinical attachment level, in all the sites were recorded.
      Untreated disease sites exhibited higher cytokine levels in the GCF when compared
      with the non-disease sites. Nonsurgical periodontal therapy resulted in a
      statistically significant decrease in the total levels of IL-1alpha, -1beta and 
      6 in the GCF, but not in IL-10 or TNF-alpha. The results support the hypothesis
      that proinflammatory cytokines, including IL-1alpha, IL-1beta and IL-6, are
      likely to be involved in the pathogenesis of periodontitis and are good markers
      to evaluate the success of nonsurgical therapy in disease sites of patients with
      periodontitis.

PMID- 24944643
TI  - Expression of hypoxia-inducible factor-1alpha, endothelin-1 and adrenomedullin in
      newborn rats with hypoxia-induced pulmonary hypertension.
AB  - Hypoxia-inducible factor (HIF)-1alpha is associated with hypoxia-induced
      pulmonary hypertension (HPH) in adults. In the present study, the expression
      levels of HIF-1alpha, endothelin (ET)-1 and adrenomedullin (ADM) were analyzed
      during HPH in neonates. In total, 96 newborn rats were subjected to hypoxia or
      normoxia for 3, 5, 7, 10, 14 or 21 days (n=8 per subgroup). HIF-1alpha, ET-1 and
      ADM expression levels were measured by quantitative polymerase chain reaction. In
      addition, the intima-media thickness/external diameter ratio (MT%) and medial
      wall cross-sectional area/vessel total cross-sectional area ratio (MA%) were
      calculated to evaluate pulmonary vascular remodeling. The mean pulmonary arterial
      pressure (mPAP) increased with exposure to hypoxia. Furthermore, the expression
      levels of HIF-1alpha, ET-1 and ADM in the lungs were shown to increase after
      three and five days of hypoxia, while the MT% and MA% increased after seven days
      of hypoxia, as compared with the controls (P<0.05). Therefore, the expression of
      HIF-1alpha, ET-1 and ADM is upregulated in the lungs of newborn rats during early
      HPH. At later stages, the mPAP increases, vascular remodeling occurs and HIF
      1alpha, ET-1 and ADM expression levels restore to normal levels.

PMID- 24944642
TI  - SOD3 and eNOS genotypes are associated with SOD activity and NOx.
AB  - Oxidative stress, characterized by increased reactive oxygen species production
      and/or decreased antioxidant enzyme activity, plays an important role in the
      pathogenesis of hypertension. The identification of molecular markers
      corresponding to the oxidative stress status of hypertension may assist in the
      antioxidant therapy of hypertension. In the present study, superoxide dismutase
      (SOD) and endothelial nitric oxide synthase (eNOS) were analyzed as markers of
      hypertension responding to oxidative stress. The plasma SOD activity and
      mononitrogen oxides (NOx) concentration were measured, and the SOD3 Ala58Thr and
      eNOS Glu298Asp polymorphisms were genotyped in hypertensive patients and
      normotensive controls. Further association experiments were replicated in an
      extended population, including 343 hypertensive patients and 290 controls. The
      results demonstrated that no statistically significant differences in the total
      SOD activity and NOx concentration were identified between the hypertensive
      patients and controls. However, the plasma SOD activity levels in the SOD3
      Ala/Ala homozygote carriers (80.51+/-27.68 U/ml) were significantly lower
      compared with the Thr allele carriers (92.18+/-16.37 U/ml; P=0.031). In addition,
      the plasma NOx concentration in the eNOS Glu/Glu homozygote carriers (129.66+/
      59.15 MUmol/l) was significantly lower compared with the Asp allele carriers
      (169.84+/- 55.18 MUmol/l; P=0.010). Notably, the altered SOD activity levels and
      NOx concentration were in concordance in 56.3% of the 80 participants. Therefore,
      the concordance of decreased SOD activity and NOx concentration, combined with
      genotypes of SOD3 Ala/Ala and/or eNOS Glu/Glu in hypertensive patients, may be
      useful in directing the antioxidant therapy of hypertension.

PMID- 24944645
TI  - Discrepancy between the effects of morronside on apoptosis in human embryonic
      lung fibroblast cells and lung cancer A549 cells.
AB  - Morroniside is a water-soluble compound extracted from the fruit of Cornus
      officinalis and is used to protect lung activity against aging. In the present
      study, the manner in which morroniside regulates normal lung and cancer cells was
      examined. The human embryonic lung fibroblast (HELF) cell line and lung cancer
      A549 cell line, and their responses to morroniside treatment, were examined.
      Results showed that morroniside reverses the apoptotic effect of H2O2 on HELF
      cell growth, protecting cell proliferation and normal cell morphology and
      inhibiting apoptosis. However, these effects were not present in A549 cells.
      Western blotting showed that morroniside also markedly downregulated
      retinoblastoma protein in HELF cells. These results suggest that morroniside
      treatment exhibits different effects on apoptosis in HELF and A549 cells, making
      it a viable compound for decreasing the side effects of anticancer medicines in
      normal cells.

PMID- 24944644
TI  - Action of melatonin on squamous cell carcinoma and other tumors of the oral
      cavity (Review).
AB  - Melatonin (MLT; N-acetyl-5-metoxy-tryptamine) is a hormone that is principally
      synthesized in the pineal gland. MLT has been shown to exhibit a variety of
      functions. The hormone, which is a free radical scavenger, plays an
      immunomodulatory role, stimulates the proliferation and synthesis of type I
      collagen and promotes bone formation. Moreover, MLT exerts oncostatic activity
      through several biological mechanisms, including antiproliferative functions,
      stimulation of anticancer immunity, modulation of oncogene expression and anti
      inflammatory, antioxidant and antiangiogenic effects. In addition, MLT inhibits
      human cancer cell growth in culture, and previous clinical studies have also
      confirmed its anticancer properties in vivo. With regard to the underlying
      mechanisms of MLT in tumor processes, including oral cavity tumors such as
      epidermoid carcinoma, knowledge of the role played by the MT1 and 2 membrane
      receptors, MT3 and the calmodulin cytosolic binding sites, as well as the nuclear
      receptors of the RZR/ROR family, is increasing. It has been hypothesized that
      exogenous restoration of MT1 (MTNR1A) expression inhibits the growth of oral
      squamous cell carcinoma cells lacking the expression of the receptor. The tumor
      suppressing functions of MLT and the presence of the MT1 receptor in various
      tumors indicate that the receptor may play a pivotal role in oral carcinogenesis.
      The current review discusses the clinical significance of MLT in oral cancer.

PMID- 24944647
TI  - Effect of CXCL12/CXCR4 on increasing the metastatic potential of non-small cell
      lung cancer in vitro is inhibited through the downregulation of CXCR4 chemokine
      receptor expression.
AB  - Lung cancer ranks as the most common type of cancer in males worldwide. Although
      great advances have been achieved in chemotherapy and radiotherapy, the long-term
      survival rate of lung cancer patients has not improved significantly.
      Dissemination of lung cancer in the thoracic cavity and metastatic spread to the
      liver, bone and brain are characteristic of non-small cell lung cancer (NSCLC),
      constituting the primary source of morbidity and mortality in lung cancer.
      Increasing evidence also indicates that the CXC chemokine receptor 4
      (CXCR4)/chemokine CXC motif ligand 12 (CXCL12) chemokine axis is important for
      the cell invasion and migration of lung cancer. CXCR4 is a G protein-coupled
      receptor with a major role in lymphocyte homing. Its ligand, CXCL12, is secreted
      by target organs and functions as a highly efficient chemotactic factor for T
      cells, monocytes, pre-B cells, dendritic cells and myeloid bone marrow-derived
      cells. In the current study, recombinant CXCR4-specific small interfering RNA
      pBSilence1.1 plasmids were constructed and transfected into the A549 NSCLC cell
      line in vitro. Reverse transcription polymerase chain reaction and western
      blotting revealed that CXCR4 was downregulated in transfected cells compared with
      control cells. The results of MTT and Transwell migration assays indicated that
      the specific downregulation of CXCR4 inhibited cell growth, invasiveness and
      migration. Thus, siRNA targeting of CXCR4 may effectively inhibit the effect of
      CXCL12/CXCR4 on increasing the metastatic potential of NSCLC.

PMID- 24944648
TI  - Triple-negative breast cancer frequency and type of BRCA mutation: Clues from
      Sardinia.
AB  - Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the
      risk of developing breast cancer. Among the prognostic factors currently used in
      clinical practice, the disease stage and the receptor status play a crucial role
      in the management of breast carcinoma. Triple-negative breast cancer (TNBC) has
      been classified as a disease subgroup that is negative for oestrogen,
      progesterone and HER2 receptor expression, and presents a poor prognosis. The
      present study investigated the correlation between BRCA1/2 mutations and TNBC
      status in a large series (n=726) of breast cancer patients from Sardinia. The
      BRCA mutation screening was performed on genomic DNA from peripheral blood
      samples by denaturing high-performance liquid chromatography analysis and
      automated DNA sequencing. Overall, 21/726 (2.9%) patients carried a germline
      mutation in BRCA1 or BRCA2. The TNBC phenotype was significantly associated with
      the BRCA1 mutations (P<0.001), whereas no association was found with the BRCA2
      mutations (P=0.837). With respect to patient origin within Sardinia, a
      significant inverse distribution of mutations was found; BRCA1 and BRCA2
      mutations represented 86 and 93% of the mutated cases in Southern and Middle
      Northern Sardinia, respectively (P<0.001). Patients from the geographical area
      with BRCA1 mutation prevalence presented a TNBC incidence much higher than that
      observed in cases from the area with BRCA2 mutation prevalence (12 vs. 4%,
      respectively; P=0.037). These findings further confirmed that the occurrence of
      TNBC is significantly associated with the BRCA1 mutation carrier status and that
      a different 'genetic background' may have a phenotypic impact in the onset of
      breast cancer.

PMID- 24944646
TI  - Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their
      enhanced inhibitory effect on epidermal growth factor receptor activation.
AB  - Glycosphingolipids are components of essentially all mammalian cell membranes and
      are involved in a variety of significant cellular functions, including
      proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide
      (GM3) is known to inhibit the activation of epidermal growth factor receptor
      (EGFR). In the present study, an efficient method for the total chemical
      synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3
      was developed. The structures of the synthesized compounds were fully
      characterized by high-resolution mass spectrometry and nuclear magnetic
      resonance. In analyses of EGFR autophosphorylation and cell proliferation ([3H]
      thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro
      derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity.
      Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory
      effect on DeltaEGFR, a splicing variant of EGFR that lacks exons 2-7 and is often
      found in human glioblastomas. The chemical synthesis of other GM3 derivatives
      using approaches similar to those described in the present study, has the
      potential to create more potent EGFR inhibitors to block cell growth or motility
      of a variety of types of cancer that express either wild-type EGFR or DeltaEGFR.

PMID- 24944649
TI  - Combined neuroendocrine carcinoma and adenocarcinoma in the stomach: A case
      report.
AB  - Neuroendocrine carcinoma and adenocarcinoma existing in the stomach
      simultaneously is extremely rare. This report presents a 65-year-old male patient
      who was diagnosed with three types of malignant tumors in the stomach,
      neuroendocrine carcinoma (NEC), moderately differentiated adenocarcinoma and
      mucinous adenocarcinoma. In addition, the NEC and moderately differentiated
      adenocarcinoma existed in the same lesion and, therefore, was referred to as a
      mixed adenocarcinoma - NEC tumor. The patient underwent laparoscopic-assisted D2
      radical total gastrectomy, Roux-en-Y esophagus-jejunum anastomosis and received
      FOLFOX chemotherapy for six cycles 3 weeks after surgery. Follow-up determined
      that the patient survived and was tumor-free 12 months after surgery. In
      conclusion, radical surgery combined with chemotherapy can effectively improve
      the prognosis of patients with these three specific tumor types simultaneously in
      the stomach.

PMID- 24944650
TI  - Imaging and pathological features of primary hepatic neuroendocrine carcinoma: An
      analysis of nine cases and review of the literature.
AB  - The present study aimed to analyze the imaging features and pathological basis of
      primary hepatic neuroendocrine carcinoma (PHNEC). A retrospective analysis of the
      imaging and pathological features of nine PHNEC cases was carried out at The
      Second Xiangya Hospital of Central South University (Changsha, China). The nine
      patients were subjected to dynamic contrast-enhanced computed tomography (CT)
      scanning of the liver and pathological diagnosis of the tissue samples. In
      addition, two patients were subjected to magnetic resonance imaging (MRI). CT
      scanning revealed the presence of single or multiple masses in the liver with a
      maximum diameter of 1-10 cm. These hepatic masses were of low density as showed
      by plain CT. These masses showed uneven or annular enhancement at their margins
      in the arterial phase. The venous portal phase showed consistent or declined
      enhancement and the delayed phase showed light enhancement in these masses. In
      addition, multiple intrahepatic nodules with long T1 and T2 signal intensities
      and obvious enhancement were observed by MRI in one patient, while intrahepatic
      lesions with moderate length T2 signal intensities and light enhancement not
      visible on the T1 image were observed in another patient. Pathological analysis
      revealed that the tumor cells exhibited morphological diversity.
      Immunohistochemical staining revealed that the tumor cells were chromogranin A-
      and synaptophysin-positive, and carcinoembryonic antigen-, hepatocytic antigen-
      and alpha-fetoprotein-negative. Imaging methods, including CT and MRI, are useful
      for the diagnosis of PHNEC; however, pathological examination is required for a
      final, definite diagnosis.

PMID- 24944651
TI  - hSulf-1 inhibits cell proliferation and migration and promotes apoptosis by
      suppressing stat3 signaling in hepatocellular carcinoma.
AB  - Human sulfatase-1 (hSulf-1) has been shown to desulfate cellular heparin sulfate
      proteoglycans and modulate several growth factors and cytokines. However, hSulf-1
      has not been previously shown to mediate the signal transducer and activator of
      transcription 3 (stat3) signaling pathway, which is known to regulate cell
      proliferation, motility and apoptosis. The present study investigated the role of
      hSulf-1 in stat3 signaling in hepatocellular cancer. hSulf-1 expression vector
      and stat3 small interfering RNA (siRNA) were constructed to control the
      expression of hSulf-1 and stat3 in HepG2 cells. hSulf-1 was found to inhibit the
      phosphorylation of stat3 and downregulate its targeted protein. MTT and Transwell
      chamber assays, as well as Annexin V/propidium iodide double-staining methods,
      were used to examine the effects of hSulf-1 on stat3-mediated motility,
      proliferation and apoptosis in HepG2 cells. Transfection with hSulf-1 cDNA and/or
      stat3 siRNA inhibited cell proliferation and motility, concurrent with G0/G1 and
      G2/M phase cell cycle arrest and apoptosis. Overall, the results of the current
      study suggested that hSulf-1 functions as a negative regulator of proliferation
      and migration and as a positive regulator of apoptosis in hepatocellular
      carcinoma, at least partly via the downregulation of stat3 signaling.

PMID- 24944652
TI  - Staging and monitoring of childhood rhabdomyosarcoma with flow cytometry.
AB  - Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The
      detection of contaminating RMS cells in the bone marrow (BM) is important in
      clinical staging and risk assessment. The cytological examination of the BM
      remains the gold standard for the diagnosis of RMS, but has a limited
      sensitivity. In the present study, 32 BM and two cerebrospinal fluid (CSF)
      samples from 11 patients with suspected metastasis were analyzed by flow
      cytometry (FCM) with ganglioside D2 (GD2) conjugated with fluorescein
      isothiocyanate, cluster of differentiation (CD)90-phycoerythrin, CD45-peridinin
      chlorophyll protein and CD56-allophycocyanin monoclonal antibody cocktail in
      parallel to morphological examination at diagnosis or during treatment. Five
      samples (14.7%) were positive for RMS onup morphological examination. By FCM, 16
      samples (47.1%) were positive for RMS. A significant difference was identified
      between the two methods. The four-color FCM assay successfully detected RMS cells
      in BM samples to a level of 0.01% (1 per 104 cells). RMS cells demonstrated a
      phenotype with CD56+/CD90+/CD45-/GD2- expression, which is different from the
      CD56+/CD90+/CD45-/GD2+ expression phenotype in neuroblastoma cells. The follow-up
      of four patients by FCM demonstrated that two patients became minimal residual
      disease-negative following two and four cycles of chemotherapy, respectively, and
      survived. The other two cases remained FCM-positive despite receiving four
      courses of chemotherapy and consequently succumbed to progressive disease. In
      addition, FCM analysis of the CSF samples from one patient confirmed a diagnosis
      of CSF metastasis with RMS. In conclusion, FCM may have a role not only in
      staging and monitoring the effects of therapy, but also in providing diagnostic
      confirmation of CSF metastasis with RMS.

PMID- 24944653
TI  - Hepatic epithelioid hemangioendothelioma: A comparison of Western and Chinese
      methods with respect to diagnosis, treatment and outcome.
AB  - Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor of vascular
      origin. Whether HEHE in Chinese patients exhibits similar characteristics
      compared with Western patients is not well known. The aim of the present study
      was to summarize the characteristics of HEHE in Chinese patients and identify its
      prognostic factors. In total, six patients diagnosed with HEHE at the Beijing
      Friendship Hospital between 2000 and 2012 were combined with 44 previously
      reported cases in China, retrieved from the literature between 1989 and mid-2012.
      These 50 cases from China were compared with 402 patients from Western
      populations. Prognostic factors were identified by the chi2 test and Cox
      regression analysis. The male to female ratio of the Chinese patients was 1:2.1
      with the mean age of 44.2 years (range, 22-86 years). The percentage of
      asymptomatic Chinese patients was significantly higher than in the Western
      patients (40.0 vs. 24.8%; P=0.026), and that of extrahepatic metastasis (16.0 vs.
      36.6%; P=0.005) was significantly lower in Chinese patients. On imaging study,
      capsular retraction (59.5%) and calcification (26.0%), as well as positivity of
      CD34 (93.5%) and CD31 (80.6%), were more frequently found in the Chinese
      patients. Management for the Chinese patients included liver resection (LRx;
      45.7%), liver transplantation (LTx; 5.7%), trans-catheter arterial
      chemoembolization (14.3%) and palliative treatment (34.3%). Chinese patients with
      larger-sized tumor nodules [relative risk (RR), 1.58; 95% confidence interval
      (CI), 1.032-2.422; P=0.035) and diffuse type (RR, 12.17; 95% CI, 1.595-92.979;
      P=0.016) exhibited unfavorable outcomes. In contrast to Western patients with
      HEHE, a larger number of Chinese patients were asymptomatic with less
      extrahepatic metastasis. In China, LRx is widely adopted rather than LTx. Chinese
      patients with large tumor size or diffuse type may encounter a poorer prognosis.

PMID- 24944654
TI  - Fluorodeoxyglucose uptake in laryngeal carcinoma is associated with the
      expression of glucose transporter-1 and hypoxia-inducible-factor-1alpha and the
      phosphoinositide 3-kinase/protein kinase B pathway.
AB  - High fluorodeoxyglucose (FDG) uptake by human carcinomas, including head and neck
      cancers, is associated with a poor prognosis. Glucose transporter-1 (Glut-1) is
      believed to be an intrinsic marker of hypoxia in malignant tumors. The expression
      of hypoxia-inducible factor-1alpha (HIF-1alpha) and correlated target genes,
      including Glut-1, is regulated by the phosphoinositide 3-kinase/protein kinase B
      (PI3K/Akt) pathway. However, it remains unclear whether the PI3K/Akt signaling
      pathway is involved in regulating FDG uptake directly. In the present study, 24
      consecutive patients with laryngeal carcinoma were examined pre-operatively and
      the standardized uptake values (SUV) of the laryngeal carcinomas were determined.
      Glut-1, HIF-1alpha, PI3K and phosphorylated-Akt (p-Akt) expression was detected
      by immunohistochemical staining of paraffin sections from the tumor specimens.
      Associations among SUVmax, Glut-1, HIF-1alpha, PI3K and p-Akt protein expression
      and the other clinical parameters were analyzed. The univariate analyses revealed
      a significantly shorter survival time along with higher HIF-1alpha (P=0.018) and
      PI3K (P=0.008) expression, but the survival time was not significantly correlated
      with Glut-1 or p-Akt expression. The multivariate analysis demonstrated that
      higher SUVmax (P=0.043) and PI3K expression (P=0.012) were significantly
      correlated with a poor survival time. Spearman's rank analysis showed significant
      correlations between SUVmax and HIF-1alpha (r=0.577; P=0.003), PI3K (r=1.0;
      P<0.0001) and p-Akt (r=0.577; P=0.003) expression. PI3K was associated with
      poorly- and moderately-differentiated laryngeal carcinoma (P=0.012). In
      conclusion, a high SUVmax indicates a poor prognosis for laryngeal carcinoma.
      Also, a high SUVmax may be associated with the increased expression of Glut-1,
      HIF-1alpha, PI3K and p-Akt.

PMID- 24944655
TI  - Relapsed acute lymphoblastic leukemia with unusual multiple bone invasions: A
      case report.
AB  - The present study describes a unique pediatric case with multiple bone invasions
      of acute lymphoblastic leukemia (ALL) during remission. An eight-year-old male
      with a history of ALL was admitted complaining of intermittent and migrating pain
      in the limb 2 years following complete remission. Magnetic resonance imaging and
      whole-body positron emission tomography with 18F-fluorodeoxyglucose revealed
      abnormal multifocal involvement in the bones and corresponding soft tissues.
      Repeated bone marrow (BM) aspiration indicated normal cellular marrow without
      leukemic cells, and marked leukemic cell infiltration in different sections of
      the ilium, respectively. These findings suggested isolated bone relapse, and it
      is probable that systematic BM relapse occurred as a consequence.

PMID- 24944656
TI  - Coexisting primary central nervous system non-Hodgkin's lymphoma and colorectal
      adenocarcinoma: A case report.
AB  - A 61-year-old female presented with night sweats following a resection for non
      Hodgkin's lymphoma of splenium corporis callosi. A positron emission tomography
      computed tomography scan demonstrated that original lymphoma activity remained. A
      new ascending colon mass was identified simultaneously, which was diagnosed as an
      adenocarcinoma following the surgery. To the best of our knowledge, this is the
      first case to report a coexistence of primary central nervous system non
      Hodgkin's lymphoma and colorectal adenocarcinoma. The case poses a difficult
      clinical challenge.

PMID- 24944657
TI  - Pulmonary sclerosing hemangioma with lymph node metastasis: A case report and
      literature review.
AB  - Pulmonary sclerosing hemangioma (SH) is an uncommon benign or low-grade malignant
      tumor. Multicentric SH and SH with lymph node metastasis have rarely been
      reported. The present report describes a case of pulmonary SH with lymph node
      metastasis in a middle-aged female. A nodule was found incidentally in the lower
      left lung. The patient underwent left lower pulmonary lobectomy and lymph node
      dissection. Histologically, the nodule demonstrated the characteristic features
      of SH and one of the resected lymph nodes contained a metastasis of this tumor.
      Thus, pulmonary SH has the potential to metastasize, a potential not suggested by
      histological features.

PMID- 24944658
TI  - A rare case of non-invasive ductal carcinoma of the breast coexisting with
      follicular lymphoma: A case report with a review of the literature.
AB  - The double presentation of breast cancer and follicular lymphoma is extremely
      rare, and only six cases have previously been reported in the literature. In the
      present study, a case of synchronous ductal carcinoma in situ (DCIS) of the
      breast and follicular lymphoma is reported. During an annual breast screening
      procedure, a 49-year-old female presented with a hard induration under the nipple
      of the right breast and swelling of a soft lymph node (LN) in the right axilla.
      Mammography and ultrasonography revealed two lesions in the right breast: One was
      a tumor with microcalcification, 1.0 cm in diameter, and the other was a large,
      crude calcification, 2.5 cm in diameter. In addition, computed tomography and
      positron emission tomography revealed swellings of the bilateral axillary (Ax) LN
      and intra-abdominal para-aortic LN. The patient underwent excisions of the large
      calcified mass, a micro-calcified tumor and the right AxLN. The pathological and
      immunohistochemical studies revealed fat necrosis and DCIS of the breast, which
      was positive for the estrogen receptor and the progesterone receptor, while human
      epidermal growth factor receptor II protein expression was evaluated as 2+ and
      stage was classified as pTis pN0 M0, stage 0. Furthermore, the Ax node was
      diagnosed as follicular lymphoma, which was positive for cluster of
      differentiation (CD)20, CD79a, CD10 and B-cell lymphoma (Bcl)-2 protein, but
      negative for Bcl-6 protein. The clinical stage was classified as stage III. The
      patient was administered chemotherapy followed by radiotherapy to the conserved
      breast. Two years have passed since the surgery, and the patient is disease-free.

PMID- 24944659
TI  - Antitumor effects of high-temperature hyperthermia on a glioma rat model.
AB  - High-temperature hyperthermia (HTH) is an established treatment option for
      cancer. The aim of the present study was to reveal the exact correlation between
      HTH at temperatures of 50-70 degrees C and the resulting antitumor effects, using
      a glioma rat model. In the 60 degrees C (T-60) and 70 degrees C (T-70) HTH
      groups, tumor growth rates were significantly suppressed compared with those in
      the nontreatment (NT) group. In the 50 degrees C (T-50) HTH group, tumor growth
      rates were not suppressed compared with those in the NT group. The numbers of
      terminal dUTP nick-end labeling-positive cells in tumor tissue were significantly
      higher in the T-50, T-60 and T-70 groups than those in the NT group. The Ki-67
      positive areas were significantly decreased in the T-70 group compared with those
      in the NT and T-60 groups. Our data indicate that HTH at 60 and 70 degrees C
      suppresses tumor growth in a glioma rat model. In particular, cell proliferation
      was significantly suppressed by HTH at 70 degrees C. However, differences in the
      mechanism of action of HTH at 60 and 70 degrees C were observed.

PMID- 24944660
TI  - Leiomyosarcoma of the thyroid gland: A case report and literature review.
AB  - Primary smooth muscle tumors of the thyroid gland are extremely rare neoplasms.
      Due to their rarity, clinical case studies concerning management are lacking.
      According to a literature review, only 19 cases of primary thyroid
      leiomyosarcomas (TLs) have been reported. In the majority of patients, the
      prognosis is poor since adjuvant radiochemotherapy is ineffective on local
      recurrence and on long-term survival. In this study, we report the case of a 77
      year-old male affected by a rapidly enlarging mass of the anterior neck,
      associated with bilateral lung metastases, and increasing dysphagia and dyspnea
      during the previous 6 months. A Tir4 neoplasm fine needle cytological diagnosis
      of the right thyroid lobe was reached and the patient underwent total
      thyroidectomy (TT). Definitive histological examination identified a TL. The
      patient succumbed 40 days later due to respiratory distress. A literature review
      was performed and TL differential diagnoses, management, including alternative
      treatment strategies, and adjuvant therapy were analyzed. TL is an aggressive
      rare mesenchymal malignant tumor. Although an improved multimodal approach is
      often necessary, TT and neck dissection represent the treatment of choice and are
      often the only possible therapy. Adjuvant radiochemotherapy appears to be
      ineffective and a high mortality rate is observed. TL remains a fatal tumor, and
      innovative and more effective therapeutic strategies to improve management and
      outcomes are required.

PMID- 24944661
TI  - FDG-PET/CT imaging for tumor staging and definition of tumor volumes in radiation
      treatment planning in non-small cell lung cancer.
AB  - 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed
      tomography (CT) has the potential to improve the staging and radiation treatment
      (RT) planning of various tumor sites. However, from a clinical standpoint,
      questions remain with regard to what extent PET/CT changes the target volume and
      whether PET/CT reduces interobserver variability in target volume delineation.
      The present study analyzed the use of FDG-PET/CT images for staging and evaluated
      the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT
      in patients with non-small cell lung cancer (NSCLC) who were candidates for
      radiotherapy. Intraobserver variation in delineating tumor volumes was also
      observed. In total, 23 patients with stage I-III NSCLC were enrolled and treated
      with fractionated RT-based therapy with or without chemotherapy. FDG-PET/CT scans
      were acquired within two weeks prior to RT. PET and CT data sets were sent to the
      treatment planning system, Pinnacle, through compact discs. The CT and PET images
      were subsequently fused by means of a dedicated RT planning system. Gross tumor
      volume (GTV) was contoured by four radiation oncologists on CT (GTV-CT) and
      PET/CT images (GTV-PET/CT). The resulting volumes were analyzed and compared. For
      the first phase, two radiation oncologists outlined the contours together,
      achieving a final consensus. Based on PET/CT, changes in tumor-node-metastasis
      categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET
      and CT images resulted in alterations in radiation therapy planning in 12/20
      patients (60%) in comparison with CT targeting. The most prominent changes in GTV
      were observed in cases with atelectasis. For the second phase, the variation in
      delineating tumor volumes was assessed by four observers. The mean ratio of
      largest to smallest CT-based GTV was 2.31 (range, 1.01-5.96). The addition of the
      PET results reduced the mean ratio to 1.46 (range, 1.02-2.27). PET/CT fusion
      images may have a potential impact on tumor staging and treatment planning.
      Implementing matched PET/CT results reduced observer variation in delineating
      tumor volumes significantly with respect to CT only.

PMID- 24944662
TI  - Analysis of DNA methylation patterns associated with the gastric cancer genome.
AB  - The objective of the current study was to investigate the characteristics of DNA
      methylation patterns associated with the gastric cancer genome and to identify
      clinically useful diagnostic markers and therapeutic targets for gastric cancer.
      The Infinium 450K methylation microarray was used to compare differential DNA
      methylation sites of gastric cancer tissue with that of normal gastric tissue.
      The results of the DNA microarray analysis were confirmed by pyrosequencing.
      Functional analysis of the differential genes was performed using the GO
      software. The effect of candidate site methylation on gene expression was
      monitored using quantitative polymerase chain reaction analysis. Of the 2,645
      differential methylation sites identified in gastric cancer tissues, 2,016 were
      hypermethylated sites, 629 were hypomethylated sites, 826 were located in
      promoter regions and 1,024 were located within genes. These differential sites
      were associated with 1,352 genes. In total, five sites were selected and
      pyrosequencing verified the results of the microarray analysis in five of the
      sites. Change in gastric cancer DNA methylation pattern was a common occurrence.
      Differential methylation sites appeared more often in non-promoter regions. The
      associated genes were involved in multiple signaling pathways, and
      hypermethylated and hypomethylated sites were involved in roughly the same
      signaling pathways. Methylation of the genome promoted gene expression. TRIM15,
      ITGAM, MSX2 and FAM38A may be candidate genes for diagnosing gastric cancer.

PMID- 24944663
TI  - Expression of vascular endothelial growth factor-C and vascular endothelial
      growth factor receptor-3 in esophageal squamous cell carcinoma.
AB  - Lymph node metastasis is one of the most important prognostic factors in
      esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor
      (VEGF)-C and its receptor, VEGF receptor-3 (VEGFR-3), are key in the process of
      lymphangiogenesis. The present study immunohistochemically examined the
      expression of VEGF-C, VEGFR-3 and D2-40 in 119 patients with ESCC, and
      microlymphatic vessel density (MLVD) was calculated based on D2-40 expression
      counts. Positive expression of VEGF-C was found to correlate significantly with
      depth of tumor invasion, lymphatic invasion and lymph node metastasis (P<0.001,
      P<0.0001 and P<0.0001, respectively). Patients with deeper tumor invasion showed
      higher positivity of VEGFR-3 expression (P<0.05), while patients with lymph node
      metastasis showed higher MLVD (P<0.05). When patients were divided into three
      groups according to the expression of VEGF-C and VEGFR-3, patients with
      coexpression of VEGF-C and VEGFR-3 exhibited poorer prognosis and higher MLVD.
      The VEGF-C/VEGFR-3 axis is important in tumor lymphangiogenesis.

PMID- 24944664
TI  - A furin inhibitor downregulates osteosarcoma cell migration by downregulating the
      expression levels of MT1-MMP via the Wnt signaling pathway.
AB  - This study aimed to explore the exact mechanism of the effect of a furin
      inhibitor on the migration and invasion of MG-63 and Saos-2 osteosarcoma cells.
      MG-63 and Saos-2 osteosarcoma cells were treated with regular culture medium in
      the presence or absence of 480 nM alpha1-antitrypsin Portland (alpha1-PDX). Wound
      healing and Transwell assays were used for the detection of the effects of alpha1
      PDX on MG-63 and Saos-2 osteosarcoma cell migration and invasion. Western blot
      analysis and reverse transcription-polymerase chain reaction were performed to
      detect the expression levels of membrane type I matrix metalloproteinase (MT1
      MMP), Wnt and beta-catenin. A chromatin immunoprecipitation assay was used for
      detection of the levels of MT1-MMP gene transcription activity. The results
      showed that alpha1-PDX treatment significantly reduced the migration and invasion
      ability of the cells. Notably, the expression levels of MT1-MMP decreased
      evidently upon alpha1-PDX treatment, paralleled with reductions in the expression
      levels of Wnt and beta-catenin. Further analysis of the transcriptional activity
      of MT1-MMP revealed that the alpha1-PDX-induced downregulation of the levels of
      MT1-MMP was mediated by the Wnt signaling pathway. These data suggest that alpha1
      PDX plays a vital role in inhibiting MG-63 and Saos-2 osteosarcoma cell migration
      and invasion by downregulating the expression levels of MT1-MMP via the Wnt
      signaling pathway.

PMID- 24944665
TI  - Successful pregnancy following conservative management of low-grade endometrial
      stromal sarcoma: A case report.
AB  - It is uncommon that fertility is preserved in young nulliparous females with low
      grade endometrial stromal sarcoma (ESS). Therefore, successful pregnancy
      following such conservative management has been rarely reported in previous
      literature. A 25-year-old female (gravida, 0; para, 0) underwent hysteroscopic
      surgery and was pathologically diagnosed with an endometrial stromal nodule. The
      patient underwent fertility-preserving local resection and uterine
      reconstruction, with a final pathological diagnosis of low-grade ESS. Endocrine
      therapy was then administered. Conservative management resulted in the complete
      remission of low-grade ESS. The patient naturally conceived and successfully
      delivered a healthy baby at 42 weeks' gestation by cesarean section, ~30 months
      following diagnosis with low-grade ESS. In conclusion, conservative management,
      including fertility-preserving local mass resection and endocrine therapy, can be
      effective for low-grade ESS and may yield a favorable outcome for young
      nulliparous females desiring fertility preservation.

PMID- 24944666
TI  - Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression.
AB  - It has been demonstrated that microRNA (miR)-133a is downregulated in a number of
      human malignancies and is closely associated with the progression of tumors. The
      present study was conducted to investigate the contribution of miR-133a to the
      initiation and malignant progression of human epithelial ovarian cancer (EOC).
      Quantitative polymerase chain reaction was employed to detect the expression of
      miR-133a in the human EOC OVCAR-3 cell line, normal human ovarian surface
      epithelial (tsT) cells and 96 tissue samples, including 70 EOC tissues and 26
      normal ovarian tissue sections. Additionally, analysis of the correlation between
      miR-133a levels and clinicopathological characteristics was carried out. The
      effect of miR-133a on cell viability, apoptosis, invasion and migration was
      investigated following transfection with miR-133a mimics and negative control
      small interfering RNA in OVCAR-3 cells. Marked downregulation of miR-133a was
      observed in the OVCAR-3 cell line and primary tumor samples, and it was found
      that reduced miR-133a expression significantly correlated with advanced clinical
      stages, poor histological differentiation and lymph node metastasis. Furthermore,
      OVCAR-3 cell viability, invasion and migration were significantly inhibited,
      while cell apoptosis was increased, following transfection of miR-133a mimics.
      The present study reveals the critical role that miR-133a plays in EOC
      pathogenesis and development, indicating that it may act as a promising biomarker
      for predicting EOC progression and as a potential target for gene therapy.

PMID- 24944667
TI  - Pancreatic body adenocarcinoma with neuroendocrine tumor characteristics: A case
      report.
AB  - A 61-year-old female with pancreatic body cancer underwent a distal
      pancreatectomy. The tumor was a moderately- to poorly-differentiated
      adenocarcinoma. Tumor growth filled the dilated main pancreatic duct (MPD) and
      infiltrated the surrounding area. Six months later, metastases to the left
      diaphragm and MPD of the remnant pancreatic head were detected. Chemoradiotherapy
      was administered, but the patient succumbed 22 months after surgery. An autopsy
      demonstrated that a moderately- to poorly-differentiated adenocarcinoma had
      arisen from the pancreatic head and infiltrated the duodenum and bile duct. Huge
      liver metastases and multiple peritoneal disseminations were also present.
      Microscopically, a portion of the tumor had a pseudo-rosette appearance in the
      adenocarcinoma component, while another section showed characteristics of a
      neuroendocrine tumor (NET) immunohistochemically. The original surgically
      resected tumor also showed NET characteristics immunohistochemically. It is
      therefore necessary to search for NET components in pancreatic cancer with
      atypical growth and metastases, even when adenocarcinoma has been diagnosed
      histologically.

PMID- 24944669
TI  - Squamous cell carcinoma arising from an unknown primary site metastasizing to the
      stomach: A case report.
AB  - Primary squamous cell carcinoma (SCC) may originate elsewhere in the body,
      including the head, neck, lung, bronchus, cervix uteri, esophagus and cardia, and
      metastasize to the stomach. In the present report, a case is presented of an SCC,
      which arose from an unknown primary site and metastasized to the stomach of a 59
      year-old male. The tumor was located in the interspace between the liver and the
      stomach. It involved the placenta percreta, lamina muscularis and submucosa,
      however, had already metastasized to a regional lymph node at the time of
      surgery. No SCC was observed in other organs on physical examination, which
      included positron emission tomography-computed tomography. In the follow-up
      period, there was no evidence of additional malignant tumors in the patient;
      therefore, the origin of the tumor was speculative. To the best of our knowledge,
      this is the first case report regarding a tumor of this type.

PMID- 24944668
TI  - Hydroxychloroquine facilitates autophagosome formation but not degradation to
      suppress the proliferation of cervical cancer SiHa cells.
AB  - Hydroxychloroquine (HCQ), the hydroxylated analog of chloroquine, is an
      antimalarial lysomotropic agent that inhibits autophagy due to lysosomal
      acidification, and subsequently blocks the fusion of autophagosomes with
      lysosomes which leads to the accumulation of autophagosomes that may accelerate
      tumor cell death. Given these hypothesis the aim of this study was to investigate
      the effects of HCQ in the inhibition of autophagy and the induction of apoptosis
      in cervical cancer SiHa cells. Cervical cancer SiHa cells were cultured with
      Hank's balanced salt solution (HBSS) as positive control of autophagy or treated
      with HCQ as part of the experimental groups. LC3 and P62/SQSTM1 were detected by
      quantitative polymerase chain reaction (qPCR) and western blotting, respectively
      in order to evaluate initially autophagosome formation and their degradation.
      Specific green fluorescent protein (GFP)-LC3 was subsequently detected by
      fluorescence microscopy in order to confirm the formation of autophagosomes. MTT
      and flow cytometry were adopted respectively to assess the proliferation and
      apoptosis of the SiHa cells. miRNA-9* was also investigated. The results
      demonstrated that HCQ increased the expressions of LC3 mRNA and LC3II protein and
      GFP-LC3 signalling but reduced the expression of p62/STSQM1 in cervical cancer
      SiHa cells. These results indicated HCQ has the ability to inhibit autophagy as
      incapable of degrading the autophagosome. However, HCQ may promote SiHa cell
      apoptosis as the MTT, apoptotic assay and miRNA-9* results revealed. HCQ has the
      ability to inhibit autophagy by blocking the degradation of autophagosomes and
      subsequently facilitates the apoptosis of cervical cancer SiHa cells.

PMID- 24944670
TI  - Clinicopathological findings in a case series of abdominopelvic solitary fibrous
      tumors.
AB  - Solitary fibrous tumors (SFTs) represent a rare type of soft tissue tumor.
      Extrathoracic SFTs (ESFTs) in the soft tissues of the abdominopelvic cavity are
      extremely rare. Between January 2002 and January 2013, 10 patients were
      identified with abdominopelvic SFTs at the Northern Jiangsu People's Hospital.
      The clinicopathological data, treatment and follow-up results were
      retrospectively analyzed in this study. Patients included four females and six
      males, whose age ranged between 21 and 75 years (mean, 53.3 years). The maximum
      diameter of the tumors was 2.5-28 cm (mean, 12.7 cm). Two cases were diagnosed as
      malignant variants of ESFTs. R0 resection was performed in eight patients, while
      one patient underwent R1 resection, and one patient received palliative
      chemotherapy for an inoperable mass. Follow-up time ranged between 6 and 126
      months (mean, 50 months). The patient with R1 resection suffered a local relapse,
      and the patient receiving palliative chemotherapy succumbed to the disease. The
      remaining eight patients remained free of disease. Abdominopelvic SFTs usually
      reveal an indolent process, although the majority of tumors in the present study
      were of giant size when diagnosed. The risk of local recurrence and metastasis
      correlates with tumor size and the histological status of surgical margins. The
      preferred treatment is complete resection followed by extended follow-up
      surveillance.

PMID- 24944671
TI  - Downregulation of hnRNP K by RNAi inhibits growth of human lung carcinoma cells.
AB  - Lung cancer is one of the most common malignancies worldwide, but its
      pathogenesis remains unknown. The current study examined the effects of
      heterogeneous nuclear ribonucleoprotein K (hnRNP K)-targeted small interfering
      RNA (siRNA) on the growth and apoptosis of lung cancer cells in vitro. The
      expression of hnRNP K was studied by the SP method of immunohistochemistry in
      lung tissue samples of 70 cases of lung cancer. hnRNP K siRNA were transfected
      into human lung cancer cell line, A549, using Lipofectamine 2000. Cells
      transfected with siRNAn and untreated served as controls. The inhibitory effect
      of siRNA on the expression of hnRNP K mRNA and protein was detected by reverse
      transcription polymerase chain reaction and western blot analysis. The change in
      cell cycling and cell apoptosis of siRNA-treated cells was detected by flow
      cytometry. The rates of positive hnRNP K expression in lung tumors of diameters
      <=3, 3-5 and >=5 cm, were 38.5, 95.2 and 91.7%, respectively. A significant
      difference was identified between lung tumors with diameters of <=3 and >=3 cm
      (P<0.01). The expression of hnRNP K mRNA was significantly inhibited in siRNA
      transfected cells compared with that in control cells (P<0.05). Notably, hnRNP K
      protein decreased in hnRNP K siRNA-transfected cells, but exhibited no effect on
      the control groups. siRNA targeting human hnRNP K effectively inhibited the
      growth of lung cancer cell line, A549, and the distribution of the cell cycle.
      The apoptosis rate was 4.79% and the number of cells increased in the G0/G1 phase
      from 37.21 to 85.60% and decreased in the S and G2/M phases from 47.71 to 13.50%
      and 14.00 to 0.32%, respectively, following 24 h of transfection. hnRNP K siRNA
      promotes A549 apoptosis and the apoptosis rate was 4.79% (P<0.01). Therefore,
      hnRNP K siRNA may inhibit the proliferation of A549 cells. In addition, hnRNP K
      promotes the growth of lung cancer cells and, therefore, hnRNP K siRNA may
      inhibit the growth and increase the apoptosis of lung cancer cells.

PMID- 24944672
TI  - Aberrant expression of redox protein Ape1 in colon cancer stem cells.
AB  - Ape1 is an important redox protein, essential for specific cytokine-induced
      signal transduction. Ape1 signaling is also important in regulating the growth of
      cancer cells, including colon cancer cells. The present study investigated
      whether Ape1 signaling plays a role in the regulation of colon cancer stem cell
      (CCSC) growth. The results showed that Ape1 was aberrantly expressed in CCSCs, as
      determined by quantitative (q)PCR assay. A laser confocal microscopy assay
      demonstrated that the Ape1 protein was mainly distributed in the nuclei, but not
      the cytoplasm, of the CSCs. Treatment of CCSCs with Ape1 redox inhibitor (E3330)
      significantly affected growth in vitro. In colon cancer xenograft mice, in vivo
      administration of E3330 enhanced tumor responses to the chemotherapeutic drug, 5
      fluorouracil (5-FU). Furthermore, the combination of E3330 and 5-FU evidently
      increased the cytotoxicity of 5-FU in CSC growth. In the qPCR assay, the CCSCs
      were demonstrated to express the dominant ATP-binding cassette sub-family G
      member 2 (ABC-G2), but not the multidrug resistance 1, genes. Thus, we
      hypothesized that drug resistance in CCSCs is mediated by ABC-G2. Since CSCs are
      involved in cancer metastasis, the Ape1 inhibitor may be a potential agent in the
      inhibition of colon cancer growth and metastasis.

PMID- 24944673
TI  - Nested PCR for mtDNA-4977-bp deletion and comet assay for DNA damage - a combined
      method for radiosensitivity evaluation of tumor cells.
AB  - To identify an effective method of evaluating the radiosensitivity of human tumor
      cell lines in vitro, the present study adopted mtDNA-4977-bp deletion coupled
      with comet assay. The three human tumor cell lines applied were HepG2, EC-9706
      and MCF-7. The surviving fraction (SF), ratio of the mtDNA-4977-bp deletion and
      DNA damage were detected by MTT assay, nested polymerase chain reaction (PCR)
      technique and comet assay, respectively. Clearly, lower SFs were found for the
      HepG2 and EC-9706 cells as compared with the MCF-7 cells following irradiation at
      doses of 2, 4 and 8 Gy, indicating a higher radiosensitivity for the HepG2 and EC
      9706 cells. Additionally, no significant differences were identified in the mtDNA
      4977-bp deletions found among HepG2, EC-9706 and MCF-7 cells by PCR following 1-
      or 4-Gy gamma-ray irradiation, while increased deletion ratios of mtDNA-4977 bp
      were observed in HepG2 and EC-9706 cells following 8-Gy irradiation, in contrast
      to decreases in MCF-7 cells. The most notable differences among these three tumor
      cell lines were observed by comet assay following 8-Gy gamma-ray irradiation. A
      combined method of nested PCR and comet assay, therefore, is the most effective
      and accurate method in evaluating the radiosensitivity of tumor cells.

PMID- 24944674
TI  - BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma:
      Association with low expression of BRCA1, improved survival and co-expression of
      DNA methyltransferases.
AB  - The breast cancer susceptibility gene 1 (BRCA1) inactivation in sporadic
      epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is
      associated with promoter hypermethylation. The clinical validation of BRCA1
      methylation as a prognostic marker in EOC remains unresolved. The aim of the
      present study was to determine the aberrant promoter methylation of BRCA1 in
      benign and malignant ovarian tumor tissues, to establish the association with the
      clinicopathological significance and the prognostic value. Additionally, the
      contribution of DNA methyltransferase (DNMT) expression to BRCA1 promoter
      hypermethylation was determined. The rate of BRCA1 methylation was observed to be
      35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the
      benign tumors. BRCA1 methylation was significantly associated with the
      downregulation of BRCA1 expression (P<0.001) and the frequency of BRCA1
      methylation was greater in the carcinomas of patients whose tumor was bilateral
      than that of patients with a unilateral carcinoma (P=0.015). BRCA1 methylation
      was significantly associated with the preoperative serum carbohydrate antigen-125
      level (P=0.013), improved overall survival (P=0.005) and disease-free survival
      (P=0.007). In addition, a significant correlation was observed between the co
      expression of DNMTs and the methylation status of BRCA1. Thus, the present study
      provided support for BRCA1 promoter hypermethylation as a prognostic marker for
      survival in sporadic EOC, and co-expression of DNMTs was observed to contribute
      to BRCA1 promoter hypermethylation.

PMID- 24944675
TI  - Lymphadenoma of the salivary gland: Report of 10 cases.
AB  - Lymphadenoma of the salivary gland is rare, and the typical characteristics of
      lymphadenoma remain poorly understood. The aim of this study was to analyze the
      experience of a single institution in the clinical diagnosis, treatment and
      prognosis of this type of tumor of the salivary gland. All cases of lymphadenoma
      diagnosed at the institution between 1996 and 2012 were analyzed. The clinical
      information (including age, gender and tumor location, process of tumor
      development, imaging data, surgical treatment and follow-up information) and
      pathological features were evaluated. All tumors occurred in the parotid glands;
      three cases were sebaceous lymphadenoma (two male and one female) and seven were
      non-sebaceous lymphadenoma (three male and four female). The average ages of the
      patients were 68.3 and 42.4 years for the sebaceous and non-sebaceous groups,
      respectively. The majority of cases (90%) were diagnosed as pleomorphic adenoma
      or adenolymphoma prior to surgery, but were confirmed as lymphadenoma by
      pathological analysis following surgery. During the follow-up period, which
      ranged between 3 and 36 months with a mean of 30 months, no recurrence of the
      lesion was identified and the quality of life was good for each patient. In
      conclusion, the diagnosis of salivary gland lymphadenoma should be based on the
      clinical and, in particular, the pathological manifestations of the disease.
      Immunohistochemistry is considered as a practical and helpful adjuvant method of
      the diagnosis for this type of tumor. Complete surgical resection is the first
      choice of treatment. Further exploration of the histological origin of
      lymphadenoma of the salivary gland is necessary due to the insufficient number of
      reported cases.

PMID- 24944676
TI  - Twist2 contributes to cisplatin-resistance of ovarian cancer through the AKT/GSK
      3beta signaling pathway.
AB  - Cisplatin is regularly used in the treatment of ovarian cancer. However, the drug
      only provides a modest survival advantage, primarily due to chemoresistance and
      the upregulation of antiapoptotic machineries in ovarian cancer cells. Therefore,
      targeting the mechanisms responsible for cisplatin resistance in ovarian cancer
      cells may improve the therapeutic outcomes. Twist basic helix-loop-helix
      transcription factor 2 (Twist2) is a novel zinc finger transcription factor that
      has been indicated to be an important inducer of epithelial-mesenchymal
      transition, which has been shown to be involved in various phases of
      tumorigenicity and progression. However, whether Twist2 suppression increases the
      chemosensitivity of ovarian cancer cells to chemotherapeutic agents remains
      unclear. In the present study, Twist2 expression was found to differ between
      human ovarian cisplatin-sensitive cancer cell line, OV2008, and the resistant
      variant, C13K cells. Twist2 plasmids or RNA interference were then utilized to
      alter Twist2 expression in OV2008 or C13K cells, respectively, to further assess
      apoptosis, cell viability and cell growth, as well as a possible mechanism. The
      results of the present study indicated that Twist2 plays a crucial role in the
      chemoresistance of ovarian cancer. In addition, the downregulation of Twist2
      expression may facilitate apoptosis and recover the sensitivity of chemoresistant
      ovarian cancer through the protein kinase B/glycogen synthase kinase-3beta
      pathway. Therefore, Twist2 depletion may be a promising approach to ovarian
      cancer therapy.

PMID- 24944677
TI  - Clinicopathological roles of adiponectin and leptin receptors in endometrial
      carcinoma.
AB  - To clarify the roles of adiponectin receptor (AdipoR) and leptin receptor (ObR)
      in endometrial carcinoma, the expression of AdipoR-1 and -2 and ObR in
      endometrial cancer was examined immunohistochemically, and correlations with
      clinicopathological implications were also analysed. Paraffin-embedded tissues
      were obtained from 77 patients with endometrial carcinoma and were stained
      immunohistochemically using antibodies against AdipoR-1, AdipoR-2 and ObR. AdipoR
      1, AdipoR-2 and ObR were localised predominantly in the cell membrane and
      cytoplasm of tumour cells and normal endometrial cells. In 77 cases of
      endometrial cancer, positive expression was observed in 46 cases (59.7%) for
      AdipoR-1, 47 cases (61.0%) for AdipoR-2 and 33 cases (42.9%) for ObR. Expression
      of AdipoR-1 was observed most in stage I cases, G1 tumours, tumours with shallow
      myometrial invasion, tumours negative for lymphovascular space involvement, cases
      negative for adnexal invasion and cases with no lymph node metastasis. However,
      the expression of AdipoR-2 and ObR showed no correlation with any
      clinicopathological factors. Kaplan-Meier analyses revealed that progression-free
      and overall survival times were longer in cases with positive AdipoR-1 expression
      compared with negative AdipoR-1 expression. Poor expression of AdipoR-1, thus,
      appears to be associated with tumour grade, myometrial invasion, adnexal
      invasion, lymph-vascular space involvement and lymph node metastasis, as well as
      poor prognosis, in endometrial cancer.

PMID- 24944678
TI  - Prognostic significance of epidermal growth factor receptor in locally advanced
      esophageal squamous cell carcinoma for patients receiving chemoradiotherapy.
AB  - The aim of the current study was to investigate the prognostic significance of
      epidermal growth factor receptor (EGFR) in patients with locally advanced
      esophageal squamous cell carcinoma (ESCC) receiving concurrent chemoradiotherapy
      (CCRT). In total, 47 patients with locally advanced ESCC who were treated with
      CCRT were included in the present study. The chemotherapeutics comprised of 5
      fluorouracil (750-1,000 mg/m2/day; days one to five) and cisplatin (30 mg/m2/day;
      days one to three) in combination with radiation therapy (~60 Gy), which was
      performed as the initial treatment. EGFR expression was compared with the
      clinicopathological features, local recurrence, metastasis status and overall
      survival (OS). Overall, EGFR overexpression (percentage of immunoreactive tumor
      cells, >=50%) was identified in 59.6% of the patients. The median survival time
      (MST) of the EGFR-positive group was 15 months and the MST of the EGFR-negative
      group was 23.5 months. A significant correlation was observed between EGFR
      overexpression and poor OS (P=0.024). EGFR overexpression was found to exhibit a
      correlation with lymph node metastasis (P=0.011), but no correlation was
      identified with other clinicopathological features. In addition, a correlation
      was identified between OS and gender (P=0.021), age (P=0.018), depth of invasion
      stage (P=0.035) and tumor location (P=0.023). EGFR overexpression determined by
      pretreatment biopsy may be a clinically useful biomarker for predicting the OS of
      ESCC patients.

PMID- 24944679
TI  - Cyclin D1 expression is correlated with cell differentiation and cell
      proliferation in oral squamous cell carcinomas.
AB  - The present study conducted an immunohistochemical investigation of cyclin D1 and
      Ki-67 expression in oral squamous cell carcinoma (SCC) to evaluate the
      correlations between cell differentiation, cell proliferation and metastasis, and
      the effect of anticancer drug medication and cyclin D1 expression. Cyclin D1 and
      Ki-67 were detected clearly in the nuclei of 35 SCC samples. No correlation
      between cyclin D1 protein expression and oral SCC differentiation was found. By
      contrast, the majority of metastatic foci (90%) exhibited strong cyclin D1
      expression, whereas weak expression was observed in metastatic foci with pre
      operative adjuvant therapy. Additionally, cyclin D1 and Ki-67 were expressed in
      basal to suprabasal cells of well-differentiated oral SCC, whereas cyclin D1
      positive and Ki-67-negative cells were present in the highly-differentiated
      region, according to a double-immunostaining method. These results indicate that
      the expression of cyclin D1 protein plays a role in cell differentiation and cell
      proliferation in well-differentiated oral SCC.

PMID- 24944681
TI  - Chromosome 8q as the most frequent target for amplification in early gastric
      carcinoma.
AB  - Early gastric carcinoma (GC) is considered to be a curable cancer, as it
      progresses to the advanced stage following varying durations. Understanding the
      early stage of GC may provide an insight into its pathogenesis and contribute to
      reducing the mortality rate of this disease. To investigate the genomic
      aberrations associated with 22 cases of early GC, high-density microarray
      comparative genomic hybridization was performed in the present study. The most
      notable finding was copy number gains (log2 ratio >0.25) on the long arm of
      chromosome 8, which occurred in 77.3% (17/22) of GC cases, and the delineated
      minimal common region was 8q22.1-q24.3. More specifically, two amplified (log2
      ratio >1) loci in the 8q22.1-q24.3 region were detected in 18.2% (4/22) of GC
      cases. The first loci covered a region of 102.4-107.9 kb, mapping on 8q22.3
      q23.1, and comprised the transcription factor CP2-like 3 gene. The second loci,
      spanning 128.7-145.7 kb on 8q24.21-q24.3, comprised the representative oncogene
      of myelocytomatosis. Furthermore, the following possible target genes that were
      not previously considered to play a pathogenic role in GC were identified:
      Plasmacytoma variant translocation 1, cysteine/histidine rich 1, kinesin family
      member C2, forkhead box H1, protein phosphatase 1 regulatory subunit 16A,
      glutamic-pyruvate transaminase, LOC113655 and RecQ protein-like 4. In the present
      study, previous findings showing that 8q mutations accumulate early during the
      multistage pathogenesis of GC were confirmed and expanded upon. The confirmation
      of previously reported 8q gains and the identification of novel target genes at
      8q22.1-q24.3 amplified chromosomal sites should aid in improving our
      understanding of the molecular mechanisms underlying the tumorigenesis of early
      GC.

PMID- 24944682
TI  - Recurrent primary haemangiopericytoma of the bladder: A case report and
      literature review.
AB  - Haemangiopericytoma (HPC) is a rare soft-tissue tumour with great histological
      variability and unpredictable clinical and biological behaviour. HPC of the
      bladder is exceedingly rare and carries uncertain malignant potential. The
      current study reports a case of HPC of the bladder in a 48-year-old female, who
      was admitted to the Sir Run Run Shaw Hospital (Hangzhou, China) due to a large
      bladder mass. The patient exhibited no mass-related symptoms, such as pain, gross
      haematuria or urinary irritation. Seven years prior to admission, the patient
      underwent surgical resection of a bladder mass, which was determined to be HPC.
      Computed tomography scans showed a well-defined, heterogeneously enhancing solid
      cystic mass in the bladder. The patient underwent complete excision of the tumour
      and a partial cystectomy. The histopathological diagnosis was HPC of the bladder.
      The post-operative recovery was uneventful and no evidence of recurrence or
      metastasis was identified during two years of follow-up. The clinical and
      histological features, and the treatment and prognosis of this tumour are
      discussed together in the present study, with a review of the literature.

PMID- 24944680
TI  - TSG101 and PEG10 are prognostic markers in squamous cell/adenosquamous carcinomas
      and adenocarcinoma of the gallbladder.
AB  - The clinicopathological characteristics of squamous cell/adenosquamous carcinoma
      (SC/ASC) are currently not well documented, and as the prevalence of SC/ASC is
      uncommon in gallbladder cancers, a prognostic marker has not yet been found. In
      the present study, the expression of tumor susceptibility gene (TSG) 101 and
      paternally expressed gene (PEG) 10 was assessed in 46 SC/ASCs and 80
      adenocarcinomas (ACs) using immunohistochemistry, and the samples were further
      analyzed to examine correlations with the clinicopathological characteristics. It
      was demonstrated that positive TSG101 and PEG10 expression were significantly
      associated with large tumor size, high tumor-node-metastasis (TNM) stage, lymph
      node metastasis, invasion and no resection (only biopsy) of SC/ASC and AC. The
      univariate Kaplan-Meier analysis showed that positive TSG101 and PEG10
      expression, and differentiation, tumor size, TNM stage, lymph node metastasis,
      invasion and surgical curability, is closely associated with a decreased overall
      survival in SC/ASC and AC patients (P<0.05 or P<0.001). The multivariate Cox
      regression analysis identified that positive TSG101 and PEG10 expression are
      independent factors for a poor-prognosis in SC/ASC and AC patients. The present
      study indicates that positive TSG101 and PEG10 expression are closely associated
      with the clinical, pathological and biological behaviors, and a poor prognosis in
      gallbladder cancer.

PMID- 24944683
TI  - Effects of photodynamic hyperthermal therapy with indocyanine green on tumor
      growth in a colon 26 tumor-bearing mouse model.
AB  - The present study used indocyanine green (ICG) and a broadband light source
      apparatus [photodynamic hyperthermal therapy (PHT) group] in order to treat a
      colon 26 tumor-bearing mouse model. The other groups were administered either ICG
      alone (ICG group), light alone (light group) or no treatment (control group).
      Following the treatment, tumor growth was measured. Nine days after the
      treatment, the tumors were resected and histological and immunohistological
      examinations were performed. In the PHT group, the growth rates of the tumor
      tissues were significantly decreased compared with those observed in the other
      groups (P<0.05). The proportion of necrotic areas in the PHT and light groups
      were increased significantly compared with those observed in the ICG and control
      groups. However, there were no significant differences between the PHT and light
      groups. The proportion of Ki-67 in the PHT and light groups was less than that
      observed in the ICG and control groups. The number of terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells in the
      PHT group was significantly increased compared with that observed in the other
      groups. These data indicate that PHT is effective in vivo and in vitro.

PMID- 24944684
TI  - Phase I randomized double-blind placebo-controlled single-dose safety studies of
      Bowman-Birk inhibitor concentrate.
AB  - In previously performed animal studies and Phase I-II human trials, Bowman-Birk
      inhibitor concentrate (BBIC) appeared to be a promising cancer chemopreventive
      agent. The present study describes the results of two phase I randomized double
      blind placebo-controlled trials performed in male subjects to assess the safety
      and toxicity of the original and new formulations of BBIC administered in a
      single dose as a suspension in orange juice. The dose of BBIC varied from 800
      2,000 chymotrypsin inhibitor (CI) units. The BBI concentration in the serum
      samples collected from the subjects was analyzed by a dot-blot analysis procedure
      using the 5G2 monoclonal antibody, which is specific for reduced BBI. A total of
      41 subjects were enrolled, 20 in the initial BBIC study and 21 in the second BBIC
      study. In these human trials, no clinically relevant changes in hematological or
      biochemical parameters were observed. Overall, BBIC was found to be well
      tolerated. For these BBIC single-dose phase I trials, there was no dose-limiting
      toxicity for BBIC, even at the highest dose evaluated, and there were no apparent
      differences between the clinical trial results for the two formulations of BBIC.
      The bioavailability of BBI in the second clinical trial, which used the new BBIC
      formulation, was approximately 40 to 43% of the BBI bioavailability reached in
      the first clinical trial, which used the original BBIC formulation. The observed
      bioavailability difference was attributed to the different BBIC formulations used
      in these two clinical trials. These trials demonstrated that BBIC is safe when
      administered in a single dose of up to 2,000 CI units. Therefore, the results
      from the two trials indicate that a multi-dose trial of BBIC may be safely
      performed with doses of up to 2,000 CI units per day.

PMID- 24944685
TI  - Anticancer effect of salidroside on A549 lung cancer cells through inhibition of
      oxidative stress and phospho-p38 expression.
AB  - Oxidative stress is important in carcinogenesis and metastasis. Salidroside, a
      phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent
      antioxidant properties. The aim of the present study was to investigate the roles
      of salidroside in cell proliferation, the cell cycle, apoptosis, invasion and
      epithelial-mesenchymal transition (EMT) in A549 cells. The human alveolar
      adenocarcinoma cell line, A549, was incubated with various concentrations of
      salidroside (0, 1, 5, 10 and 20 MUg/ml) and cell proliferation was detected by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Propidium
      iodide (PI) staining was used to determine the cell cycle by flow cytometry. Cell
      apoptosis was detected by Annexin V-fluorescein isothiocyanate and PI double
      staining, and tumor invasion was detected by Boyden chamber invasion assay.
      Western blot analysis was performed to detect the expression of EMT markers,
      Snail and phospho-p38. The results showed that salidroside significantly reduced
      the proliferation of A549 cells, inhibited cell cycle arrest in the G0/G1 phase
      and induced apoptosis. Salidroside inhibited transforming growth factor-beta
      induced tumor invasion and suppressed the protein expression of Snail. As an
      antioxidant, salidroside inhibited the intracellular reactive oxygen species
      (ROS) formation in a dose-dependent manner in A549 cells, and depletion of
      intracellular ROS by vitamin C suppressed apoptosis by salidroside treatment.
      Salidroside was also found to inhibit the expression of phospho-p38 in A549
      cells. In conclusion, salidroside inhibits cell proliferation, the cell cycle and
      metastasis and induces apoptosis, which may be due to its interference in the
      intracellular ROS generation, thereby, downregulating the ROS-phospho-p38
      signaling pathway.

PMID- 24944686
TI  - BxPC3 pancreatic cancer cells express a truncated Smad4 protein upon PI3K and
      mTOR inhibition.
AB  - Smad4 is a critical regulator of transforming growth factor (TGF)-beta signaling
      and is defective in numerous human cancers. In total, 30% of pancreatic cancers
      harbor a homozygous deletion of Smad4. The human pancreatic cancer cell line,
      BxPC3, has been reported to be Smad4-null due to a homozygous deletion and has
      been widely used as a Smad4-null model. The present study reports that Smad4 DNA
      is present in BxPC3 cells, and under conditions of suppressed mammalian target of
      rapamycin complex 1 (mTORC1) and phosphatidylinositol-3-kinase, a truncated Smad4
      protein is expressed. While a high level of Smad4 protein can be expressed in
      these cells, the cells do not respond to TGF-beta. The Smad4 defect in BxPC3
      cells likely occurs via translocation rather than deletion as previously
      reported.

PMID- 24944687
TI  - Prognostic significance of leukopenia in childhood acute lymphoblastic leukemia.
AB  - Chemotherapy-induced leukopenia has been shown to be associated with the outcomes
      of several types of cancer, but the association with childhood acute
      lymphoblastic leukemia (ALL) remains unknown. To elucidate the association of
      chemotherapy-induced leukopenia with the clinical outcome of childhood ALL,
      retrospective analysis was performed on 19 child patients with ALL treated
      according to the ALL-BFM 95 high-risk (HR) protocol. The mean minimum leukocyte
      count over the first three courses of the consolidation phase was used as the
      measure of hematological toxicity and ranged between 200 and 1,167/MUl. The risk
      of relapse was significantly higher in patients with a mean minimum leukocyte
      count above the median of 433/MUl (hazard ratio, 6.61; P=0.047). In conclusion,
      chemotherapy-induced leukopenia was found to correlate with relapse-free survival
      in childhood HR ALL. Dose escalation based on hematologic toxicity must be
      prospectively studied.

PMID- 24944688
TI  - Wnt/beta-catenin signaling pathway may regulate the expression of angiogenic
      growth factors in hepatocellular carcinoma.
AB  - The Wnt/beta-catenin signaling pathway plays a key role during hepatocellular
      carcinoma (HCC) genesis and development. The present study aimed to investigate
      the effects of the Wnt/beta-catenin signaling pathway on the expression of
      angiogenic growth factors involved in HCC. The HCC HepG2 cell line was
      transfected with small interfering RNA (siRNA) against beta-catenin. After 72 and
      96 h, protein was extracted and the expression levels of beta-catenin, matrix
      metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF)-A,
      VEGF-C and basic fibroblast growth factor (bFGF) were detected by western blot
      analysis. beta-catenin protein expression was inhibited at both time points.
      Notably, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF protein expression levels
      decreased at 72 h and then increased at 96 h after transfection. Our results
      demonstrated that in HCC cells, the Wnt/beta-catenin signaling pathway may
      regulate the protein expression of the angiogenic factors, MMP-2, MMP-9, VEGF-A,
      VEGF-C and bFGF. These proteins were downstream of beta-catenin signaling and
      were also regulated by other factors. In conclusion, the Wnt/beta-catenin
      signaling pathway may contribute to the regulation of HCC angiogenesis,
      infiltration and metastasis through regulating the expression of these angiogenic
      factors.

PMID- 24944689
TI  - Functionally active rat S100A4 from a polymerase chain reaction-synthesized gene
      expressed in soluble form in Escherichia coli.
AB  - S100A4 protein is associated with Ca2+-dependent regulation of intracellular
      activities and is significant in the invasion, growth and metastasis of cancer.
      In order to express rat S100A4 functionally and identify its biological activity
      following purification, an S100A4 gene fragment was optimized and fully
      synthesized via overlapping polymerase chain reaction. The gene was inserted into
      the prokaryotic expression vector, pBV220, with phage lambda PRPL promoters
      following confirmation by DNA sequencing. The pBV220-S100A4 plasmid was
      constructed and transformed into Escherichia coli DH5alpha. Following temperature
      induction, rat S100A4 was overexpressed and the protein was observed to be
      located in the supernatant of the lysates, which was ~30-40% of the total protein
      within the host. The protein was isolated and purified by metal-chelate affinity
      chromatography. High purity protein (>98% purity) was obtained and in vitro
      western blot analysis identified that the recombinant S100A4 was able to bind to
      the antibody against wild-type S100A4. The bioactivity of the recombinant protein
      was detected via Transwell migration and invasion assays. The polyclonal antibody
      of rat S100A4 protein was prepared for rabbit immunization and exhibited similar
      efficacies when compared with commercial S100A4. Therefore, rat S100A4 was
      functionally expressed in E. coli; thus, the production of active recombinant
      S100A4 protein in E. coli may further aid with the investigation and application
      of S100A4.

PMID- 24944690
TI  - Clinical outcomes and prediction of survival following percutaneous biliary
      drainage for malignant obstructive jaundice.
AB  - The present study aimed to investigate the clinical outcomes of percutaneous
      transhepatic biliary drainage in patients with obstructive jaundice and identify
      potential predictors of patient survival. Clinical data from 102 patients (66
      males and 36 females; median age, 63.50 years; range, 29-84 years) with a mean
      (+/- standard deviation) pre-drainage serum bilirubin level of 285.4 (+/-136.7
      MUmol/l), were retrospectively studied. Technical and clinical success,
      complications and survival time were recorded and their relationship with
      clinical factors, including age, obstruction level, liver metastases, serum
      bilirubin level and subsequent treatments following drainage, were analyzed by
      Fisher's exact test. Patient survival rate and other predictors were analyzed by
      Kaplan-Meier survival curves and Cox's proportional hazard model. The technical
      and clinical success rates were 100 and 76.5%, respectively. The presence of
      liver metastases was associated with reduced successful drainage. The overall
      complication rate was 7.8% and the overall median survival time was 185 days [95%
      confidence interval (CI), 159-211 days]. A log-rank test showed that age (chi2,
      4.003; P=0.04), bilirubin levels following procedure (chi2, 5.139; P=0.02) and
      subsequent therapy (chi2, 15.459; P=0.00) affected survival time. However, Cox's
      regression analysis revealed no administration of additional treatments to be a
      risk factor of survival (odds ratio, 2.323; 95% CI, 1.465-3.685; P=0.000).
      Percutaneous transhepatic biliary drainage for malignant biliary obstruction was
      found to be a safe and effective method to relieve jaundice caused by progressive
      neoplasms. Subsequent radical therapy following drainage, including surgery,
      chemotherapy and other local treatment types, are likely to increase patient
      survival.

PMID- 24944691
TI  - Effect of pregnane X receptor expression on drug resistance in breast cancer.
AB  - This study was conducted to investigate the effect of increased expression of the
      nuclear transcription factor receptor pregnane X receptor (PXR) on drug
      resistance of breast cancer cells. Western blotting was used to detect the
      expression of PXR in breast carcinoma cells. The PXR agonist SR12813 was used to
      upregulate the expression of PXR. Semi-quantitative polymerase chain reaction was
      used to detect PXR gene expression in normal and cancerous breast tissues, as
      well as the expression levels of the drug-resistant genes multidrug resistance
      protein 1 (MDR1) and breast cancer resistance protein (BCRP) in breast cancer
      cells. A Cell Counting Kit-8 assay was used to observe the sensitivity of the
      breast cancer cells to chemotherapeutic agents. Flow cytometry was used to
      investigate cell apoptosis. PXR expression was detected in normal and cancerous
      human breast tissues and in breast cancer cell lines. SR12813 treatment led to an
      increased expression of PXR protein and an increased expression of drug-resistant
      genes, MDR1 and BCRP, in MCF-7 and MDA-MB-231 cells. SR12813 pretreatment
      significantly increased the resistance of MDA-MB-231 cells to docetaxel. A marked
      increase in resistance to 4-hydroxytamoxifen was also observed in MCF-7 with
      SR12813 pretreatment. Additionally, we also found that pretreatment with SR12813
      led to reduced apoptosis of the two cell strains induced by chemotherapeutic
      agents. In conclusion, PXR expression has an important effect on the sensitivity
      to chemotherapy of PXR-positive breast carcinoma. The inhibitory effect of PXR on
      cell apoptosis may contribute to the drug resistance of breast carcinoma.

PMID- 24944692
TI  - Long noncoding RNA expression signatures of bladder cancer revealed by
      microarray.
AB  - Dysregulation of long noncoding RNAs (lncRNAs) has been regarded as a primary
      feature of several human cancers. However, the genome-wide expression and
      functional significance of lncRNAs in bladder cancer remains unclear. The aim of
      this study was to identify aberrantly expressed lncRNAs that may play an
      important role in contributing to bladder cancer pathogenesis. In this study, we
      described lncRNAs profiles in four pairs of human bladder cancer and matched
      normal bladder tissues by microarray. We finally determined 3,324 differentially
      expressed human lncRNAs and 2,120 differentially expressed mRNAs (>=2-fold
      change). A total of 110 lncRNAs were significantly differentially expressed
      between the tumor and the control groups (>=8-fold change). Four lncRNAs (TNXA,
      CTA-134P22.2, CTC-276P9.1 and KRT19P3) were selected for further confirmation of
      microarray results using quantitative PCR (qPCR), and a strong correlation was
      identified between the qPCR results and microarray data. We also observed that
      numerous lncRNA expression levels were significantly correlated with the
      expression of tens of protein coding genes by construction of the lncRNA-mRNA co
      expression network. Kyoto Encyclopedia of Genes and Genomes annotation showed a
      significant association with p53, bladder cancer, cell cycle and propanoate
      metabolism pathway gene expression in the bladder cancer group compared with the
      normal tissue group, indicating that deregulated lncRNAs may act by regulating
      protein-coding genes in these pathways. We demonstrated the expression profiles
      of human lncRNAs in bladder cancer by microarray. We identified a collection of
      aberrantly expressed lncRNAs in bladder cancer compared with matched normal
      tissue. It is likely that these deregulated lncRNAs play a key or partial role in
      the development and/or progression of bladder cancer.

PMID- 24944693
TI  - Involvement of SET in the Wnt signaling pathway and the development of human
      colorectal cancer.
AB  - The SET oncoprotein is involved in cancer progression by modulating multiple
      cellular processes, including the inhibition of the tumor suppressor, protein
      phosphatase 2 (PP2A). Based upon these multiple activities, we hypothesized that
      targeted inhibition of SET is likely to have multiple discrete and measurable
      effects on cancer cells. In the present study, the mRNA expression levels of SET,
      PP2A and beta-catenin were examined in 31 pairs of human colorectal
      adenocarcinoma tissues and corresponding adjacent normal colorectal tissues by
      quantitative real-time polymerase chain reaction (qPCR). A small interfering RNA
      targeting SET was transfected into the human colon carcinoma cell lines, LS174T
      and SW480. The mRNA levels of SET, PP2A, beta-catenin, c-Myc, E-cadherin and p53
      were determined by qPCR analysis and the protein levels of SET, c-Myc, PP2A and
      beta-catenin were examined by western blot analysis. mRNA expression levels of
      SET and beta-catenin were found to be elevated in 22 (70.9%) samples, while PP2A
      expression levels were upregulated in eight (25.8%) samples. In addition, the
      knockdown of SET mRNA expression caused the upregulation of PP2A and c-Myc in the
      two cell lines, whereas beta-catenin, E-cadherin and p53 mRNA expression was
      downregulated. Consistent with these results, the protein expression of beta
      catenin and c-Myc was found to be downregulated, whereas PP2A was upregulated at
      the protein level. Based on these results, we proposed that SET is essential in
      the carcinogenesis of human colorectal adenocarcinoma. In addition, it is
      suggested that SET promotes carcinogenesis through regulation of the Wnt
      signaling pathway.

PMID- 24944694
TI  - Related to testes-specific, vespid and pathogenesis protein-1 is regulated by
      methylation in glioblastoma.
AB  - Related to testes-specific, vespid and pathogenesis protein-1 (RTVP-1), also
      known as glioma pathogenesis-related protein 1, is highly expressed and has
      oncogenic features in glioblastoma (GBM; World Health Organization class IV).
      Promoter methylation has been found to control RTVP-1 expression in prostate
      carcinoma, Wilms' tumor, acute myeloid leukemia and melanoma. In this bi
      institutional study, the methylation status of RTVP-1 in astrocytic brain
      malignancies (GBM and oligodendroglioma) was examined. The RTVP-1 promoter was
      hypomethylated in GBM compared with non-tumor brain samples, but was
      hypermethylated in oligodendroglioma. RTVP-1 methylation correlated with RTVP-1
      expression at the mRNA level. In GBM, hypermethylation of the RTVP-1 promoter was
      associated with improved overall survival although with no statistical
      significance.

PMID- 24944695
TI  - Comparison of the clinical outcomes of laparoscopic-assisted versus open surgery
      for colorectal cancer.
AB  - The present study aimed to compare the clinical outcomes of laparoscopic-assisted
      surgery versus open surgery for colorectal cancer and investigate the oncological
      safety and potential advantages and disadvantages of laparoscopic-assisted
      surgery for colorectal cancer. The medical records from a total of 160 patients
      who underwent surgery for colorectal cancer between January 2009 and January 2013
      at The Second Hospital of Dalian Medical University (Dalian, China) were
      retrospectively analyzed. The patients who underwent laparoscopic-assisted
      surgery showed significant advantages due to the minimally invasive nature of the
      surgery compared with those who underwent open surgery, namely, less blood loss
      (P=0.002), shorter time to flatus (P<0.001), bowel movement (P=0.009) and liquid
      diet intake (P=0.015), earlier ambulation time (P=0.006), smaller length of
      incision (P<0.001) and a shorter post-operative hospital stay (P=0.007). However,
      laparoscopic-assisted surgery for colorectal cancer resulted in a longer
      operative time (P=0.015) and higher surgery expenditure (P=0.003) and total
      hospitalization costs (P<0.001) compared with open surgery. There were no
      statistically significant differences between the intraoperative and post
      operative complications. There were no differences in the local recurrence
      (P=0.699) or distant metastasis (P=0.699) rates. In addition, no differences were
      found in overall survival (P=0.894) and disease-free survival (P=0.701). These
      findings indicated that laparoscopic-assisted surgery for colorectal cancer had
      the clear advantages of a minimally invasive surgery and relative disadvantages,
      including a longer surgery time and higher cost, and exhibited similar rates of
      recurrence and survival compared with open surgery.

PMID- 24944696
TI  - microRNA-99a inhibiting cell proliferation, migration and invasion by targeting
      fibroblast growth factor receptor 3 in bladder cancer.
AB  - The expression of microRNA-99a (miRNA-99a) has been investigated in a number of
      human cancers. It has been reported to be downregulated in several types of
      cancer, including ovarian carcinoma, squamous cell carcinoma of the tongue,
      squamous cell lung carcinoma, hepatocellular carcinoma, bladder cancer, prostate
      cancer and childhood adrenocortical tumors. In the present study, the effects of
      miRNA-99a on bladder cancer cell proliferation, migration and invasion were
      examined. Following transfection of miRNA-99a, cell viability, cell migration
      assay, cell invasion, western blot analysis and luciferase assays were conducted
      in bladder cancer cell lines. It was found that miRNA-99a inhibits cell
      proliferation, migration and invasion in T24 and EJ cells. Additionally, this
      study provided the first evidence that miRNA-99a is likely to directly target
      fibroblast growth factor receptor 3 in bladder cancer. The study provided
      evidence that miRNA-99a suppresses cell proliferation, migration and invasion by
      targeting growth factor receptor 3 in bladder cancer cell lines. These results
      indicated that it could be investigated as a target for therapeutic drugs
      designed to treat bladder cancer.

PMID- 24944697
TI  - Spontaneous complete regression of multiple metastases of hepatocellular
      carcinoma: A case report.
AB  - Spontaneous regression of cancer is a partial or complete disappearance of
      malignant tumor without specific treatment. Spontaneous regression of
      hepatocellular carcinoma (HCC) is a rare condition, and the mechanism underlying
      it is unclear. This report presents a rare case of spontaneous complete
      regression of HCC, as revealed by tumor markers and imaging studies. A 64-year
      old Korean male patient with hepatitis B virus-associated chronic hepatitis
      presented with HCC. The patient had undergone right lobectomy of the liver but
      the cancer recurred with multiple lung and adrenal metastases after 14 months.
      The patient received palliative cytotoxic chemotherapy. However, there was no
      clinical benefit and the disease progressed. It was decided to discontinue
      anticancer therapy and administer only supportive care. After approximately six
      months, the symptoms disappeared and the HCC had completely regressed. The
      patient remains alive over five years after recurrence.

PMID- 24944698
TI  - Effect of tumor suppressor gene cyclin-dependent kinase inhibitor 2A wild-type
      and A148T mutant on the cell cycle of human ovarian cancer cells.
AB  - Single-base substitution may affect the function of genes. This study identified
      a single-base substitution of G for A in codon 148 of cyclin-dependent kinase
      inhibitor 2A (CDKN2A/p16) by sequencing human ovarian cancer cell line UACC-1598.
      As a tumor suppressor gene, the expression of CDKN2A/p16 should be strictly
      controlled. In order to control CDKN2A/p16 gene expression, an inducible pTUNE
      vector system was selected. Using recombinant DNA technology, a CDKN2A/p16-A148T
      and CDKN2A/p16-wild-type gene expression system was successfully constructed to
      investigate whether this single-base substitution affects the function of
      CDKN2A/p16. For the wild-type and the mutant, expression of CDKN2A/p16-green
      fluorescent protein fusion protein increased markedly following isopropyl-beta-D
      thiogalactoside induction, and was accompanied by significant G1 arrest in the
      transfected human ovarian cancer SKOV3 cell line. The inducible vectors used in
      this study, CDKN2A/p16-wild-type and CDKN2A/p16-A148T open reading frame, may be
      useful for further investigation into whether this somatic mutation could alter
      the function of CDKN2A/p16 as a tumor suppressor gene. In summary, CDKN2A/p16
      A148T was identified in ovarian cancer cells, and this single-base substitution
      did not affect the ability of CDKN2A/p16 to arrest the cell cycle.

PMID- 24944699
TI  - microRNA-503 inhibits gastric cancer cell growth and epithelial-to-mesenchymal
      transition.
AB  - Epithelial-to-mesenchymal transition (EMT) is believed to be associated with
      cancer cell malignancy, and also to cause cancer invasion and metastasis. Recent
      evidence indicates that small non-protein coding RNA [microRNAs (miRNAs/miRs)]
      may act as powerful regulators of EMT. The present study aimed to systematically
      delineate miR-503 expression in gastric cancer and analyse the function of miR
      503 in gastric cancer EMT. In the present study, miR-503 expression was detected
      in gastric cancer cell lines and gastric cancer tissues by quantitative
      polymerase chain reaction. Gastric cancer cell migration, invasion and
      proliferation capabilities were analysed by Transwell, MTT and clonability
      assays. The expression of mesenchymal markers, including fibronectin, vimentin, N
      cadherin, SNAIL and the epithelial marker, E-cadherin, was examined by immunoblot
      analysis following miR-503 transfection. miR-503 expression was found to be
      reduced in gastric cancer cell lines compared with normal gastric mucosa cell
      lines, and the expression of miR-503 was upregulated in non-metastatic-derived
      gastric cancer cell lines compared with metastatic-derived lines. miR-503
      expression levels were significantly reduced in tumour tissues in comparison with
      adjacent normal mucosa tissues, and the miR-503 expression levels in patients
      with metastases were significantly lower than those in patients without. miR-503
      inhibited gastric cancer cell migration, invasion and proliferation. Fibronectin,
      vimentin, N-cadherin and SNAIL protein levels were decreased, but E-cadherin
      expression was increased in an AGS cell line transfected with miR-503. Taken
      together, the present findings indicate that miR-503 acts as a novel tumour
      suppressor gene in gastric cancer and can inhibit EMT in gastric cancer cells.

PMID- 24944700
TI  - Abundant expression of HMGB1 in human T-cell lymphotropic virus type I-infected T
      cell lines and high plasma levels of HMGB1 in patients with adult T-cell
      leukemia.
AB  - High mobility group box 1 (HMGB1) functions as a chromatin-associated nuclear
      protein and an extracellular signaling molecule. The concentration of HMGB1
      protein and the expression of HMGB1 mRNA were analyzed by ELISA and polymerase
      chain reaction (PCR), respectively. The present study reports high plasma HMGB1
      levels in patients with adult T-cell leukemia [ATL; which is caused by infection
      with human T-cell lymphotropic virus type I (HTLV-I)] compared with normal
      controls. In addition, HMGB1 was highly expressed in HTLV-I-infected T-cell lines
      compared with uninfected T-cell lines. The HTLV-I oncoprotein, Tax, induced
      extracellular release of HMGB1 in T cells. The results suggest that HMGB1 is a
      potential biomarker and a therapeutic target for ATL.

PMID- 24944702
TI  - Combined small cell carcinoma of the sinonasal tract associated with syndrome of
      inappropriate secretion of antidiuretic hormone: A case report.
AB  - Combined small cell carcinoma (SmCC) and squamous cell carcinoma (SqCC) is a rare
      malignant neoplasm in the head and neck. This study presents the first reported
      case of combined SmCC and SqCC originating from the sinonasal tract accompanied
      by syndrome of inappropriate secretion of antidiuretic hormone (SIADH). An 80
      year-old female presented with a four-week history of right nasal discharge,
      nasal obstruction and left neck swelling. Imaging studies revealed a tumorous
      lesion in the maxillary sinus encroaching upon the right nasal cavity and left
      cervical lymph node (LN) swelling. An incisional biopsy carried out from the
      right maxillary sinus and LNs resulted in a diagnosis of combined SmCC with SqCC,
      staged as T4aN2cM0. Clinical examination revealed a sustained increase of
      antidiuretic hormone, hyponatremia with urinary sodium increase, and serum hypo
      osmosis, resulting in SIADH. Water restriction to <1,000 ml/day was effective in
      improving sodium and osmotic imbalance. Curative treatment for the tumor was not
      prescribed due to the poor condition of the patient. Palliative treatment was
      administered and the patient succumbed to cachexia five months after histological
      diagnosis. The presence of SIADH may have marked implications for the treatment
      and prognosis of this disease.

PMID- 24944701
TI  - Pleomorphic hyalinizing angiectatic tumor arising in the thigh: A case report.
AB  - Pleomorphic hyalinizing angiectatic tumors (PHATs) are rare non-metastasizing
      tumors of uncertain lineage. The current study presents a case of PHAT arising in
      the thigh of a 68-year-old female and examines the clinicopathological
      characteristics of the tumor. Magnetic resonance imaging (MRI) revealed an
      intramuscular mass located in the adductor longus. The tumor was surrounded by
      lipomatous tumor. Wide resectioning was performed for the internal tumor, whereas
      intralesional resectioning was performed for the external tumor.
      Histopathologically, the internal lesion was diagnosed as a PHAT and the external
      lesion was diagnosed as an hemosiderotic fibrolipomatous lesion (HFLL). No
      recurrence or metastases were identified during the 6-year follow-up period. As
      the adipose tissue surrounding the PHAT resembled a HFLL, therefore, the
      association between 'early PHAT' and HFLL is discussed. Although PHATs may
      represent low-grade sarcomas, HFLLs may be benign tumors.

PMID- 24944703
TI  - Percutaneous transhepatic biliary stenting in patients with intradiverticular
      papillae and biliary strictures caused by ampullary carcinoma: A case report.
AB  - Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy is
      a well-established procedure for the treatment of bile duct strictures. However,
      the procedure is difficult to perform in patients with intradiverticular papillae
      or tumor infiltration of the major papilla. Percutaneous transhepatic biliary
      stenting (PTBS) is commonly used in the management of malignant biliary
      stricture. The current study reports two cases of PTBS performed to treat
      malignant obstructive jaundice caused by ampullary carcinoma complicated with
      intradiverticular papillae. PTBS is potentially a safe technique for this
      relatively rare condition.

PMID- 24944704
TI  - Synergistic effect of ginsenoside Rg3 with verapamil on the modulation of
      multidrug resistance in human acute myeloid leukemia cells.
AB  - The pharmacological modulatory effects of 20(S)-ginsenoside Rg3 (20S-Rg3) on
      multidrug resistant cancer cells are reported in the present study. The effects
      of 20(S)-Rg3 on the modulation of doxorubicin (DOX) and vincristine (VCR)
      resistance were examined in the HL60 multidrug resistant subline of human acute
      myeloid leukemia cells. Results demonstrated that 20S-Rg3 is as effective as
      verapamil (Vp) for modulating the high degree primary DOX resistance and low
      degree VCR cross-resistance expressed by the H160 cell line. Furthermore, the
      present study demonstrates for the first time, using isobologram analysis, that
      the combination of 20S-Rg3 and Vp enhances the reversal of DOX and VCR resistance
      in a supra-additive or at least an additive manner. These results indicate that
      20S-Rg3 may be used as a Vp synergizer or as a promising alternative to Vp in the
      chemosensitization of multidrug resistant acute myeloid leukemia, with far fewer
      side effects.

PMID- 24944705
TI  - Primary appendiceal mucinous adenocarcinoma mimicking bladder carcinoma: A case
      report and review of the literature.
AB  - Primary appendiceal mucinous adenocarcinoma is a rare entity, while appendiceal
      carcinoma invading the urinary bladder is even rarer. The current study presents
      the case of a 54-year-old male with primary appendiceal mucinous adenocarcinoma,
      without gastrointestinal symptoms, presenting only with signs of bladder
      irritation. Abdominal computed tomography scans demonstrated a mass at the right
      anterior level of the bladder. During intraoperative exploration, the mass was
      detected to connect and adhere to the ileocecal junction, and normal appendix
      tissues were not found. The frozen section revealed a mucinous adenocarcinoma of
      the appendix and the patient immediately underwent a subsequent hemicolectomy.
      The present case indicates that a diagnosis of a primary appendiceal mucinous
      carcinoma must considered by radiologists and clinicians for patients who do not
      exhibit gastrointestinal symptoms, but show involvement of the nearest organs and
      the bladder wall.

PMID- 24944706
TI  - Simultaneous bilateral testicular metastases from renal clear cell carcinoma: A
      case report and review of the literature.
AB  - Metastasis from renal cell carcinoma (RCC) to the testis is rare. This case
      report presented an extremely rare case of simultaneous bilateral testicular
      metastases from RCC in a 65-year-old man who had experienced indolent scrotal
      enlargement over a period of several months. Scrotal ultrasonography showed 4.0-
      and 2.0-cm-sized masses in the left and right testes, respectively. Contrast
      enhanced computed tomography identified multiple tumors in the kidneys, the
      pancreas and the left adrenal gland. Left orchiectomy and pathological
      examination were performed and indicated testicular metastasis from clear cell
      RCC. The patient underwent complete surgical resection of all residual lesions.
      Postoperative follow-up examination without adjuvant therapy identified no
      recurrence over 11 months. This study also reviewed existing literature and
      determined that retrograde venous spread from the primary kidney tumor to the
      testis may be an important pathway for testicular metastasis from RCC. In
      conclusion, RCC can result in testicular metastases not only unilaterally, but
      also bilaterally, as was observed in the present case.

PMID- 24944708
TI  - Construction and analysis of regulatory genetic networks in cervical cancer based
      on involved microRNAs, target genes, transcription factors and host genes.
AB  - Over recent years, genes and microRNA (miRNA/miR) have been considered as key
      biological factors in human carcinogenesis. During cancer development, genes may
      act as multiple identities, including target genes of miRNA, transcription
      factors and host genes. The present study concentrated on the regulatory networks
      consisting of the biological factors involved in cervical cancer in order to
      investigate their features and affect on this specific pathology. Numerous raw
      data was collected and organized into purposeful structures, and adaptive
      procedures were defined for application to the prepared data. The networks were
      therefore built with the factors as basic components according to their
      interacting associations. The networks were constructed at three levels of
      interdependency, including a differentially-expressed network, a related network
      and a global network. Comparisons and analyses were made at a systematic level
      rather than from an isolated gene or miRNA. Critical hubs were extracted in the
      core networks and notable features were discussed, including self-adaption
      feedback regulation. The present study expounds the pathogenesis from a novel
      point of view and is proposed to provide inspiration for further investigation
      and therapy.

PMID- 24944707
TI  - Brain metastasis in basaloid undifferentiated anal carcinoma: A case report.
AB  - Anal cancer is a rare tumor that accounts for 2% of all colorectal neoplasms. The
      brain is a rarely affected organ. The aim of the present study was to the review
      the only four cases of anal cancer brain metastases previously published in the
      literature. In addition, the current study presents the case of a 69-year-old
      male diagnosed with basaloid undifferentiated carcinoma of the anal canal (stage
      IV with liver, lung and bone metastasis). Despite the patient's good response to
      chemotherapy and the achievement of a partial response that was maintained for 14
      months, brain metastases developed. Although radiotherapy was administered, the
      patient succumbed to the condition 12 weeks after the diagnosis of brain
      metastasis.

PMID- 24944709
TI  - Rosiglitazone amplifies the sensitivity of docetaxel and reduces the expression
      of CD44v6.
AB  - Breast cancer seriously impairs physical and mental health in females. Currently,
      with further investigation into drugs, a number of new pharmacological effects
      have been found that offer new methods for clinical application in the treatment
      of breast cancer. As a widely used antidiabetic drug, rosiglitazone (Ros) has
      become well known for its anticancer effects, mediated by the activation of
      peroxisome proliferator-activated receptor gamma and downregulated expression of
      the associated invasion gene. The objective of the present study was to
      investigate the combination of Ros and docetaxel (DOC) and whether DOC has any
      effect on breast cancer cell lines. The results showed that the combination of
      Ros and DOC may cooperate to increase anti-growth efficacy. The additive
      inhibitory effects on cell proliferation were sequence-dependent and are not
      likely to be associated with cell cycle arrest. This suggested that the target
      activation of associated factors of the signaling pathway by Ros may be a
      compelling ally in cancer treatment. In addition, evidence was provided for a
      convergence of Ros and DOC to induce the reduced expression of CD44v6. Future
      studies are required to confirm which associated gene of Ros is significant in
      blocking the signaling pathway.

PMID- 24944710
TI  - Extraskeletal myxoid chondrosarcoma: A report of two cases.
AB  - Extraskeletal myxoid chondrosarcoma (EMC) is a relatively rare but well-defined
      neoplasm. This report describes two patients, one with EMC of the buttock and one
      with EMC of the knee. The two cases presented with large lobed masses and long T1
      and T2 signaling identified by magnetic resonance imaging (MRI). An enhanced MRI
      scan demonstrated enhancement of the tumors. The tumors were composed of strands
      or cords of oval and spindle cells embedded in abundant myxoid stroma. Pathology
      results confirmed EMC.

PMID- 24944711
TI  - Stereotactic body radiation therapy for centrally-located lung tumors.
AB  - The application of high-dose irradiation to centrally-located lung tumors is
      generally considered to be of high risk in causing bronchial injury. The aim of
      the present retrospective study was to investigate the safety and efficacy of
      stereotactic body radiation therapy (SBRT) for patients with centrally-located
      lung tumors. In total, 28 patients who underwent SBRT for lung tumors within 2 cm
      of a major bronchus were retrospectively analyzed. The median total dose
      prescribed was 45 Gy (range, 36.3-52.5 Gy), the median fraction was 12 (range, 10
      15) and the median dose per fraction was 3.6 Gy (range, 3-5 Gy). The median
      follow-up period for the surviving patients was 14 months (range, 10-41 months).
      The local control rate of SBRT was 100%, with a complete response (CR) rate of
      32.1% (9/28); a partial response (PR) rate of 50% (14/28) and a stable disease
      (SD) rate of 17.9% (5/28). In total, 15 patients survived and 13 patients
      succumbed; 11 patients succumbed to tumor progression, one to congestive heart
      failure and one to a brain hemorrhage. The main side-effects included grade 2
      esophagitis (17.9%; 5/28) atelectasis (10.7%; 3/28) and grade 2 late radiation
      pneumonitis (7.1%; 2/28). Severe late toxicity (>= grade 3) was not observed in
      any patient. SBRT is an effective and safe therapy for centrally-located lung
      tumors.

PMID- 24944712
TI  - Deep neck abscess as the predominant initial presentation of carcinoma of unknown
      primary: A case report.
AB  - Malignancies, which present as deep neck abscesses are uncommon and may result in
      a delayed diagnosis or potentially a misdiagnosis. The present study describes a
      patient who exhibited a deep neck abscess as the initial manifestation of
      carcinoma of unknown primary (CUP). The aim of the present study was to raise
      awareness of this unusual presentation of CUP and emphasize the importance of
      repeating targeted fine-needle aspiration cytology or biopsies in patients
      presenting with a deep neck abscess suspicious for malignancy.

PMID- 24944713
TI  - Prognosis of recurrent non-small cell lung cancer following complete resection.
AB  - Prognosis following recurrence subsequent to complete resection of non-small-cell
      lung cancer (NSCLC) is considered a multifactorial process dependent on
      clinicopathological, biological and treatment characteristics. Gefitinib was
      approved for lung cancer treatment in Japan in 2002. The aim of the current study
      was to quantify the prognostic effects of these characteristics on post
      recurrence prognosis. In total, 127 NSCLC patients were analyzed who underwent
      complete resection and subsequently had recurrent cancer. The correlation between
      characteristics of the initial and recurrent disease with post-recurrence
      prognosis was investigated. The factors clearly associated with post-recurrence
      prognosis using Cox proportional hazards models were age at recurrence (those <65
      years of age typically had better prognoses) and interval between initial
      resection and recurrence (intervals of <1 year accompanied a worse prognosis).
      Epidermal growth factor receptor (EGFR) mutant patients treated with EGFR
      tyrosine kinase inhibitors (TKIs), exhibited the longest median survival
      following recurrence (37.4 months) in the sample. Treatment, particularly EGFR
      TKIs for recurrent NSCLC, was observed to significantly prolong survival. The
      results of the study highlight that various treatment modalities according to the
      clinical background of the patient should be considered in patients with
      postoperative recurrent NSCLC.

PMID- 24944714
TI  - L-asparaginase-induced severe acute pancreatitis in an adult with extranodal
      natural killer/T-cell lymphoma, nasal type: A case report and review of the
      literature.
AB  - L-asparaginase (L-Asp)-associated pancreatitis (AAP) occurs occasionally;
      however, this side-effect has predominantly been observed among pediatric
      patients. Usually, it is not life-threatening and generally responds to intensive
      medical therapy. The present study presents a rare case of lethal AAP in an
      adult. The patient was recently diagnosed with extranodal natural killer/T-cell
      lymphoma (ENKTL), nasal type, and the chronic hepatitis B virus (HBV) infection
      and was receiving L-Asp as part of a chemotherapy regimen. Severe acute
      pancreatitis occurred and the patient succumbed 72 h after completion of
      chemotherapy. The HBV infection and lipid disorders may have been potential risk
      factors for the development of severe acute pancreatitis in the patient.

PMID- 24944716
TI  - Initial experience with GeneXpert MTB/RIF assay in the Arkansas Tuberculosis
      Control Program.
AB  - BACKGROUND: Mycobacterium tuberculosis remains one of the most significant causes
      of death from an infectious agent. Rapid and accurate diagnosis of pulmonary and
      extra-pulmonary tuberculosis (TB) is still a great challenge. The GeneXpert
      MTB/RIF assay is a novel integrated diagnostic system for the diagnosis of
      tuberculosis and rapid detection of Rifampin (RIF) resistance in clinical
      specimens. In 2012, the Arkansas Tuberculosis Control Program introduced
      GeneXpert MTB/RIF assay to replace the labour-intensive Mycobacterium
      Tuberculosis Direct (MTD) assay. AIMS: To rapidly diagnose TB within two hours
      and to simultaneously detect RIF resistance. OBJECTIVES: Describe the procedure
      used to introduce GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control
      Program.Characterise the current gap in rapid M. tuberculosis diagnosis in
      Arkansas.Assess factors that predict acid fast bacilli (AFB) smearnegative but
      culture-positive cases in Arkansas.Illustrate, with two case reports, the role of
      GeneXpert MTB/RIF assay in reduction of time to confirmation of M. tuberculosis
      diagnosis in the first year of implementation. METHOD: Between June 2012 and June
      2013, all AFB sputum smearpositive cases and any others, on request by the
      physician, had GeneXpert MTB/RIF assay performed as well as traditional M.
      tuberculosis culture and susceptibilities using Mycobacteria Growth Indicator
      Tube (MGIT) 960 and Lowenstein-Jensen (LJ) slants. Surveillance data for January
      2009-June 2013 was analysed to characterise sputum smear-negative but culture
      positive cases. RESULTS: Seventy-one TB cases were reported from June 2012- June
      2013. GeneXpert MTB/RIF assay identified all culture-positive cases as well as
      three cases that were negative on culture. Also, this rapid assay identified all
      six smear-negative but M. tuberculosis culture-positive cases; two of these cases
      are described as case reports. CONCLUSION: GeneXpert MTB/RIF assay has made rapid
      TB diagnosis possible, with tremendous potential in determining isolation of TB
      suspects on one hand, and quickly ruling out TB whenever suspected.

PMID- 24944715
TI  - Low-grade fibromyxoid sarcoma around the knee involving the proximal end of the
      tibia and patella: A rare case report.
AB  - Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive variant of fibrosarcoma.
      LGFMS is a rare soft tissue tumor that tends to develop in the deep soft tissue
      of young adults and has the potential for local recurrence or distant metastasis.
      The current case report presents a 22-year-old male complaining of a slow growing
      painless mass in the right knee over a period of 10 years. Following complete
      evaluation by radiological and histopathological examination, a diagnosis of
      LGFMS was confirmed and a wide excision was performed. Currently, the patient has
      been under follow-up for the last five years without any evidence of metastasis.
      The present case report provides further information concerning the diagnosis,
      imaging and management of LGFMS.

PMID- 24944717
TI  - Medicines shortages-unpicking the evidence from a year in South Africa.
AB  - Although medicines shortages are a persistent and challenging problem for all
      health systems, the reasons for such shortages vary considerably between
      settings. Understanding the range of problems encountered, and the specific
      reasons for each medicines shortage event, may help to identify the most
      appropriate systems-wide responses. South Africa's health system is, at this
      point, still clearly divided between a better-resourced private sector and an
      overwhelmed public sector. Medicines selection and procurement processes in the
      two sectors are markedly different. However, in both sectors there is a dearth of
      publicly accessible information about the incidence and consequences of medicines
      shortages. This brief report describes the medicines selection and procurement
      processes currently applied in South Africa's public health sector, and then
      describes the nature of the medicines shortages that have been experienced in the
      KwaZulu-Natal provincial health services between July 2012 and June 2013. The
      degree to which these shortages might have been managed differently, had the
      recommendations developed by the International Pharmaceutical Federation Summit
      on Medicines Shortages been implemented, is then explored. 

PMID- 24944718
TI  - Unilateral supernumerary kidney with contra lateral hydronephrosis-a rare case
      report.
AB  - Supernumerary kidney is the rarest of all renal anomalies; fewer than 80 cases
      have been reported in the literature over the years. Supernumerary kidneys are
      most commonly located on the left side of the abdomen. Different pathologic
      conditions are reported to affect supernumerary kidneys and they may be
      associated with malformations of the upper urinary tract and genital tract.
      Because of their infrequent occurrence and reporting, they frequently cause
      diagnostic challenges. Here we report a case in a 14-year-old male patient of
      unilateral supernumerary kidney on the right side of the abdomen with multiple
      calculi, mal-rotation and a gross hydronephrotic left kidney. 

PMID- 24944719
TI  - A qualitative study of staff perspectives of patient non-attendance in a regional
      primary healthcare setting.
AB  - BACKGROUND: Non-attendance at health appointments reduces health service
      efficiency, is costly to services, and can risk patient health. Reminder systems
      are widely used to overcome forgetfulness, the most common reason for non
      attendance; however, other factors, such as patient demographics and service
      accessibility, may also affect attendance rates. AIMS: There is limited primary
      research on the reasons for patient non-attendance in the Australian healthcare
      setting, although the success of preventative health initiatives requires ongoing
      monitoring of patients. This study aims to improve our understanding of the
      Australian experience by examining staff perspectives. METHOD: This qualitative
      study explored staff perspectives of the reasons for non-attendance in a large,
      regional general practice super clinic, which has a low socioeconomic catchment,
      and serves a large Aboriginal population. RESULTS: The practical barriers to
      attendance of travel, cost, and waiting times had largely been overcome with
      transport provision, free medical care and responsive appointment times, but
      paradoxically, these were seen to devalue allocated appointments and reinforce
      the expectations of "on-demand" health care. For Aboriginal patients
      specifically, a distrust of authority, combined with poor health literacy was
      perceived to impact negatively on the uptake of diagnostic tests, filling of
      prescriptions, health monitoring, and adherence to medication. CONCLUSION: The
      results suggest a complex interplay between poor health literacy and low patient
      self-worth; a funding system that encourages "five-minute medicine and prevents
      doctors getting to the root cause of patient problems or having the ability to
      provide health education.

PMID- 24944720
TI  - Bilateral variations of brachial plexus involving the median nerve and lateral
      cord: An anatomical case study with clinical implications.
AB  - During the routine dissection of upper limbs of a Caucasian male cadaver,
      variations were observed in the brachial plexus. In the right extremity, the
      lateral cord was piercing the coracobrachialis muscle. The musculocutaneous nerve
      and lateral root of the median nerve were observed to be branching inferior to
      the lower attachment of coracobrachialis muscle. The left extremity exhibited the
      passage of the median nerve through the flat tendon of the coracobrachialis
      muscle near its distal insertion into the medial surface of the body of humerus.
      A variation in the course and branching of the nerve might lead to variant or
      dual innervation of a muscle and, if inappropriately compressed, could result in
      a distal neuropathy. Identification of these variants of brachial plexus plays an
      especially important role in both clinical diagnosis and surgical practice. 

PMID- 24944721
TI  - Reversible lower limb deep vein thrombosis following haemotoxic snakebite-a case
      report.
AB  - Haemotoxic snakebite, presenting with coagulopathy and bleeding manifestations,
      is quite common. Thrombotic manifestations are infrequently observed. We describe
      the unusual case of a young male who developed deep vein thrombosis (DVT) of the
      left lower limb following snakebite, despite an ongoing coagulopathy.
      Investigations revealed leucocytosis, prolonged 20-minute whole blood clotting
      time (20'WBCT), prolonged prothrombin time (PT), and activated partial
      thromboplastin time (aPTT). Doppler study revealed thrombosis of common femoral
      vein, superficial femoral, and profunda femoris veins. The patient underwent two
      fasciotomies and received anticoagulation after which patency of the veins was
      restored. Doppler sonographic imaging in patients with haemotoxic snakebite who
      present with increasing local swelling may assist with early anticoagulation
      therapy that has a potential to be limb-saving. 

PMID- 24944722
TI  - Social implications of genomic medicine: Is medicine ready?

PMID- 24944723
TI  - Two adult cases of extralobar pulmonary sequestration: A non-complicated case and
      a necrotic case with torsion.
AB  - BACKGROUND: This case report describes two cases of extralobar pulmonary
      sequestration in adults with and without torsion/necrosis. CASE REPORTS: Non
      complicated extralobar pulmonary sequestration was found incidentally in a 50
      year-old asymptomatic woman (Case 1), diagnosed with the presence of a branching
      structure in a mass lesion and blood supply from the right inferior phrenic
      artery. Another case of a 38-year-old woman presented with a sudden onset of back
      pain caused by extralobar pulmonary sequestration with torsion/necrosis (Case 2).
      A 4-cm fusiform mass in the paravertebral region showed enhancement in the
      peripheral rim only, and no feeding artery. These were the same as it had been
      reported typical findings in extralobar pulmonary sequestration with necrosis. On
      magnetic resonance imaging, the masses in both cases showed inhomogeneous low
      signal and branching high signal on T2-weighted images. That was characteristic
      for a stroma without dilated alveoli as a solid part and dilated alveoli as fluid
      regions. CONCLUSIONS: By comparing those two cases, we came to a conclusion that
      only T2-weighted imaging reflects the native structure, even after infarction.
      Although differentiation from a cystic tumor with hemorrhage or infection can be
      problematic, inhomogeneous low signal and branching high signal on T2-weighted
      images may help us distinguish extralobar pulmonary sequestration from other
      cystic lesions.

PMID- 24944724
TI  - Case report of LCP pediatric hip osteosynthesis of a proximal femoral fracture in
      a child with marble bone disease.
AB  - We present a case report demonstrating the experience of the department of
      pediatric orthopaedics of the University Orthopedic Hospital at Sofia Medical
      University in the treatment of an intertrochanteric proximal femoral fracture in
      a child with osteopetrosis. We performed open fracture reduction with stable 120
      degrees  LCP (Locking Compression Plate) Pediatric hip osteosynthesis. Fracture
      consolidation and ability to walk without crutches was achieved in a half a year.
      The presented case is the first for Bulgaria. There are still no publications in
      the world literature on application of such osteosynthesis in marble bone
      disease. 

PMID- 24944725
TI  - [Multiple molluscum contagiosum of the child].

PMID- 24944726
TI  - [Limbal dermoid in Goldenhar syndrome].

PMID- 24944727
TI  - Slit ventricle syndrome and early-onset secondary craniosynostosis in an infant.
AB  - PATIENT: Female, 14 months FINAL DIAGNOSIS: Slit ventricle syndrome Symptoms:
      Hydrocephalus * lethargy and seizure * vomiting MEDICATION: - Clinical Procedure:
      - Specialty: Pediatrics and Neonatology. OBJECTIVE: Challenging differential
      diagnosis. BACKGROUND: Shunt surgery is a common solution for hydrocephalus in
      infancy. Slit ventricle syndrome and secondary craniosynostosis are late-onset
      complications after shunt placement; these 2 conditions occasionally occur
      together. CASE REPORT: We report a case of early-onset secondary craniosynostosis
      with slit ventricle syndrome after shunt surgery in an infant, which led to a
      catastrophic increase in intracranial pressure (ICP). A 4-month-old girl with a
      Dandy-Walker malformation underwent a ventriculoperitoneal shunt procedure. Her
      head circumference (HC) gradually decreased to approximately the 5(th) percentile
      for her age group after shunt surgery. Seven months later, she developed
      increased ICP symptoms and underwent a shunt revision with a diagnosis of shunt
      malfunction. Her symptoms were temporarily relieved, but she repeatedly visited
      the emergency room (ER) for the same symptoms and finally collapsed, with an
      abrupt increase in ICP, 3 months later. Further evaluation revealed the emergence
      of sagittal synostosis at 7 months after initial shunt surgery. After reviewing
      all clinical data, slit ventricle syndrome combined with secondary
      craniosynostosis was diagnosed. Emergent cranial expansion surgery with shunt
      revision was performed, and the increased ICP signs subsided in the following
      days. CONCLUSIONS: Clinical suspicion and long-term HC monitoring are important
      in the diagnosis of slit ventricle syndrome and secondary craniosynostosis after
      shunt surgery, even in infants and young children.

PMID- 24944728
TI  - Telementoring in education of laparoscopic surgeons: An emerging technology.
AB  - Laparoscopy, minimally invasive and minimal access surgery with more surgeons
      performing these advanced procedures. We highlight in the review several key
      emerging technologies such as the telementoring and virtual reality simulators,
      that provide a solid ground for delivering surgical education to rural area and
      allow young surgeons a safety net and confidence while operating on a newly
      learned technique. 

PMID- 24944729
TI  - Validity of ligand efficiency metrics.
AB  - A recent viewpoint article (Improving the plausibility of success with
      inefficient metrics. ACS Med. Chem. Lett. 2014, 5, 2-5) argued that the standard
      definition of ligand efficiency (LE) is mathematically invalid. In this
      viewpoint, we address this criticism and show categorically that the definition
      of LE is mathematically valid. LE and other metrics such as lipophilic ligand
      efficiency (LLE) can be useful during the multiparameter optimization challenge
      faced by medicinal chemists. 

PMID- 24944730
TI  - Imidazo[2,1]thiazol-3-one Derivatives Useful as Diagnostic Agents for Alzheimer's
      Disease.

PMID- 24944731
TI  - Piperazion[1,2-A]indol-1-ones and [1,4]Diazepino[1,2-A]indol-1-ones.

PMID- 24944732
TI  - Hybrid dopamine uptake blocker-serotonin releaser ligands: a new twist on
      transporter-focused therapeutics.
AB  - As part of our program to study neurotransmitter releasers, we report herein a
      class of hybrid dopamine reuptake inhibitors that display serotonin releasing
      activity. Hybrid compounds are interesting since they increase the design
      potential of transporter related compounds and hence represent a novel and
      unexplored strategy for therapeutic drug discovery. A series of N
      alkylpropiophenones was synthesized and assessed for uptake inhibition and
      release activity using rat brain synaptosomes. Substitution on the aromatic ring
      yielded compounds that maintained hybrid activity, with the two disubstituted
      analogues (PAL-787 and PAL-820) having the most potent hybrid activity. 

PMID- 24944733
TI  - Potent and orally efficacious bisthiazole-based histone deacetylase inhibitors.
AB  - Inspired by the thiazole-thiazoline cap group in natural product largazole, a
      series of structurally simplified bisthiazole-based histone deacetylase
      inhibitors were prepared and evaluated. Compound 8f was evaluated in vivo in an
      experimental autoimmune encephalomyelitis (EAE) model and found to be orally
      efficacious in ameliorating clinical symptoms of EAE mice. 

PMID- 24944734
TI  - Toward the Development of Bivalent Ligand Probes of Cannabinoid CB1 and Orexin
      OX1 Receptor Heterodimers.
AB  - Cannabinoid CB1 and orexin OX1 receptors have been suggested to form heterodimers
      and oligomers. Aimed at studying these complexes, a series of bivalent CB1 and
      OX1 ligands combining SR141716 and ACT-078573 pharmacophores were designed,
      synthesized, and tested for activity against CB1 and OX1 individually and in cell
      lines that coexpress both receptors. Compound 20 showed a robust enhancement in
      potency at both receptors when coexpressed as compared to individually expressed,
      suggesting possible interaction with CB1-OX1 dimers. Bivalent ligands targeting
      CB1-OX1 receptor dimers could be potentially useful as a tool for further
      exploring the roles of such heterodimers in vitro and in vivo. 

PMID- 24944735
TI  - Synthesis of water-soluble dinuclear mn-porphyrin with multiple antioxidative
      activities.
AB  - Superoxide dismutase (SOD) and catalase activities of a drug are of great
      importance for its effective protection against reactive oxygen species (ROS)
      induced injury. Achievement of catalase activity of a synthetic compound remains
      a challenge. Water-soluble Mn-porphyrins have high SOD and peroxynitrite (ONOO(
      )) reducing activities, but not catalase-like activity. Herein, we are able to
      retain the fair SOD-like activity of a mononuclear Mn-5-(N-methylpyridinium-4-yl)
      10,15,20-triphenyl porphyrin (MnM4PyP3P), while gaining in catalase-like activity
      with its dinuclear complex, 1,3-di[5-(N-methylene-pyridinium-4-yl)-10,15,20
      triphenyl porphynato manganese] benzene tetrachloride (MnPD). Mechanistic study
      indicates that catalase-like activity of MnPD is due to synergism of two Mn
      active sites, where hydroxo-Mn(IV) complex is formed as an intermediate. The in
      vivo experiments demonstrate that MnPD significantly restores the treadmill
      running ability of SOD-deficient mouse and thus indicates the therapeutic
      potential of MnPD. Furthermore, MnPD may serve as a mechanistic tool and indicate
      the new directions in the synthesis of catalase-like mimics. 

PMID- 24944736
TI  - Chemogenesis of an antiangiogenic glycosaminoglycan.
AB  - In this letter we report a facile chemical conversion of heparin, a potent
      anticoagulant with minimal antiangiogenic activity, into an effective
      antiangiogenic glycosaminoglycan through optimized chemical approaches. This work
      highlights the potential for industrial scale production of a therapeutic
      anticancer glycosaminoglycan. 

PMID- 24944737
TI  - Chiral Resolution and Serendipitous Fluorination Reaction for the Selective
      Dopamine D3 Receptor Antagonist BAK2-66.
AB  - The improved chiral synthesis of the selective dopamine D3 receptor (D3R)
      antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)1H
      indole-2-carboxamide (( R )-PG648) is described. The same chiral secondary
      alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl
      analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were
      assigned from their X-ray crystal structures that confirmed retention of
      configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST).
      ( R )-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer;
      however, it had lower D3R affinity and enantioselectivity than ( R )-PG648.
      Further, importance of the 4-atom linker length between the aryl amide and 4
      phenylpiperazine was demonstrated with the 4-fluorobutyl-product (8). 

PMID- 24944738
TI  - Development of [(123)I]IPEB and [(123)I]IMPEB as SPECT Radioligands for
      Metabotropic Glutamate Receptor Subtype 5.
AB  - mGlu5 play an important role in physiology and pathology to various central
      nervous system (CNS) diseases. Several positron emission tomography (PET)
      radiotracers have been developed to explore the role of mGlu5 in brain disorders.
      However, there are no single photon emission computed tomography (SPECT)
      radioligands for mGlu5. Here we report development of [(123)I]IPEB ([(123)I]1)
      and [(123)I]IMPEB ([(123)I]2) as mGlu5 radioligands for SPECT. [(123)I]1 and
      [(123)I]2 were produced by copper(I) mediated aromatic halide displacement
      reactions. The SPECT imaging using mouse models demonstrated that [(123)I]1
      readily entered the brain and accumulated specifically in mGlu5-rich regions of
      the brain such as striatum and hippocampus. However, in comparison to the
      corresponding PET tracer [(18)F]FPEB, [(123)I]1 showed faster washout from the
      brain. The binding ratios of the striatum and the hippocampus compared to the
      cerebellum for [(123)I]1 and [(18)F]FPEB were similar despite unfavorable
      pharmacokinetics of [(123)I]1. Further structural optimization of 1 may lead to
      more viable SPECT radiotracers for the imaging of mGlu5. 

PMID- 24944739
TI  - Case Study of Small Molecules As Antimalarials: 2-Amino-1-phenylethanol (APE)
      Derivatives.
AB  - Antiparasitic oral drugs have been associated to lipophilic molecules due to
      their intrinsic permeability. However, these kind of molecules are associated to
      numerous adverse effects, which have been extensively studied. Within the Tres
      Cantos Antimalarial Set (TCAMS) we have identified two small, soluble and simple
      hits that even presenting antiplasmodial activities in the range of 0.4-0.5 MUM
      are able to show in vivo activity. 

PMID- 24944740
TI  - Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.
AB  - Because of the promise of BCL-2 antagonists in combating chronic lymphocytic
      leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective
      antagonists of antiapoptotic proteins has grown. Beginning with a series of
      selective, potent BCL-XL antagonists containing an undesirable hydrazone
      functionality, in silico design and X-ray crystallography were utilized to
      develop alternative scaffolds that retained the selectivity and potency of the
      starting compounds. 

PMID- 24944741
TI  - Synthesis of [(11)C]Bexarotene by Cu-Mediated [(11)C]Carbon Dioxide Fixation and
      Preliminary PET Imaging.
AB  - Bexarotene (Targretin) is a retinoid X receptor (RXR) agonist that has
      applications for treatment of T cell lymphoma and proposed mechanisms of action
      in Alzheimer's disease that have been the subject of recent controversy. Carbon
      11 labeled bexarotene ([(11)C-carbonyl]4-[1-(3,5,5,8,8-pentamethyltetralin-2
      yl)ethenyl]benzoic acid) was synthesized using a Cu-mediated cross-coupling
      reaction employing an arylboronate precursor 1 and [(11)C]carbon dioxide under
      atmospheric pressure in 15 +/- 2% uncorrected radiochemical yield (n = 3), based
      on [(11)C]CO2. Judicious choice of solvents, catalysts, and additives, as well as
      precursor concentration and purity of [(11)C]CO2, enabled the preparation of this
      (11)C-labeled carboxylic acid. Formulated [(11)C]bexarotene was isolated (>37
      mCi) with >99% radiochemical purity in 32 min. Preliminary positron emission
      tomography-magnetic resonance imaging revealed rapid brain uptake in nonhuman
      primate in the first 75 s following intravenous administration of the radiotracer
      (specific activity >0.3 Ci/MUmol at time of injection), followed by slow
      clearance (Delta = -43%) over 60 min. Modest uptake (SUVmax = 0.8) was observed
      in whole brain and regions with high RXR expression. 

PMID- 24944742
TI  - Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2:
      Synthesis, SAR, and Cellular Activity.
AB  - Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report
      a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine
      scaffold. Two novel synthetic protocols were employed for rapid analoguing of the
      designed molecules for structure-activity relationship (SAR) exploration. Some
      analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic
      level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent
      antiproliferative effect against c-Met addictive cell lines with IC50 values
      ranged from 0.33 to 1.7 MUM. In addition, a cocrystal structure of c-Met in
      complex with 3h has been determined, which reveals the binding mode of c-Met to
      its inhibitor and helps to interpret the SAR of the analogues. 

PMID- 24944743
TI  - Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents.
AB  - Nucleoside analogues have long been recognized as prospects for the discovery of
      direct acting antivirals (DAAs) to treat hepatitis C virus because they have
      generally exhibited cross-genotype activity and a high barrier to resistance. C
      Nucleosides have the potential for improved metabolism and pharmacokinetic
      properties over their N-nucleoside counterparts due to the presence of a strong
      carbon-carbon glycosidic bond and a non-natural heterocyclic base. Three 2'CMe-C
      adenosine analogues and two 2'CMe-guanosine analogues were synthesized and
      evaluated for their anti-HCV efficacy. The nucleotide triphosphates of four of
      these analogues were found to inhibit the NS5B polymerase, and adenosine analogue
      1 was discovered to have excellent pharmacokinetic properties demonstrating the
      potential of this drug class. 

PMID- 24944745
TI  - Diamine Derivatives as Novel Small-Molecule, Potent, and Subtype-Selective
      Somatostatin SST3 Receptor Agonists.
AB  - A novel class of small-molecule, highly potent, and subtype-selective
      somatostatin SST3 agonists was discovered through modification of a SST3
      antagonist. As an example, (1R,2S)-9 demonstrated not only potent in vitro SST3
      agonist activity but also in vivo SST3 agonist activity in a mouse oral glucose
      tolerance test (OGTT). These agonists may be useful reagents for studying the
      physiological roles of the SST3 receptor and may potentially be useful as
      therapeutic agents. 

PMID- 24944746
TI  - Novel and high affinity fluorescent ligands for the serotonin transporter based
      on (s)-citalopram.
AB  - Novel rhodamine-labeled ligands, based on (S)-citalopram, were synthesized and
      evaluated for uptake inhibition at the human serotonin, dopamine, and
      norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding
      at SERT, in transiently transfected COS7 cells. Compound 14 demonstrated high
      affinity binding and selectivity for SERT (K i = 3 nM). Visualization of SERT,
      using confocal laser scanning microscopy, validated compound 14 as a novel tool
      for studying SERT expression and distribution in living cells. 

PMID- 24944744
TI  - Synthesis, Characterization, and in Vitro Evaluation of a New TSPO-Selective
      Bifunctional Chelate Ligand.
AB  - The 18-kDa translocator protein (TSPO) is overexpressed in many types of cancers
      and is also abundant in activated microglial cells occurring in inflammatory
      neurodegenerative diseases. Thus, TSPO has become an extremely attractive
      subcellular target not only for imaging disease states overexpressing this
      protein, but also for a selective mitochondrial drug delivery. In this work we
      report the synthesis, the characterization, and the in vitro evaluation of a new
      TSPO-selective ligand, 2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4
      chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide (CB256), which
      fulfils the requirements for a bifunctional chelate approach. The goal was to
      provide a new TSPO ligand that could be used further to prepare coordination
      complexes of a metallo drug to be used in diagnosis and therapy. However, the
      ligand itself proved to be a potent tumor cell growth inhibitor and DNA double
      strand breaker. 

PMID- 24944747
TI  - Discovery of Novel Imidazo[4,5-b]pyridines as Potent and Selective Inhibitors of
      Phosphodiesterase 10A (PDE10A).
AB  - We report the discovery of novel imidazo[4,5-b]pyridines as potent and selective
      inhibitors of PDE10A. The investigation began with our recently disclosed
      ketobenzimidazole 1, which exhibited single digit nanomolar PDE10A activity but
      poor oral bioavailability. To improve oral bioavailability, we turned to novel
      scaffold imidazo[4,5-b]pyridine 2, which not only retained nanomolar PDE10A
      activity but was also devoid of the morpholine metabolic liability. Structure
      activity relationship studies were conducted systematically to examine how
      various regions of the molecule impacted potency. X-ray cocrystal structures of
      compounds 7 and 24 in human PDE10A helped to elucidate the key bonding
      interactions. Five of the most potent and structurally diverse imidazo[4,5
      b]pyridines (4, 7, 12b, 24a, and 24b) with PDE10A IC50 values ranging from 0.8 to
      6.7 nM were advanced into receptor occupancy studies. Four of them (4, 12b, 24a,
      and 24b) achieved 55-74% RO at 10 mg/kg po. 

PMID- 24944748
TI  - Synthesis of Aspartame by Thermolysin: An X-ray Structural Study.
AB  - Protease mediated peptide synthesis (PMPS) was first described in the 1930s but
      remains underexploited today. In most PMPS, the reaction equilibrium is shifted
      toward synthesis by the aqueous insolubility of product generated. Substrates and
      proteases are selected by trial and error, yields are modest, and reaction times
      are slow. Once implemented, however, PMPS reactions can be simple,
      environmentally benign, and readily scalable to a commercial level. We examined
      the PMPS of a precursor of the artificial sweetener aspartame, a multiton peptide
      synthesis catalyzed by the enzyme thermolysin. X-ray structures of thermolysin in
      complex with aspartame substrates separately, and after PMPS in a crystal,
      rationalize the reaction's substrate preferences and reveal an unexpected form of
      substrate inhibition that explains its sluggishness. Structure guided
      optimization of this and other PMPS reactions could expand the economic viability
      of commercial peptides beyond current high-potency, low-volume therapeutics, with
      substantial green chemistry advantages. 

PMID- 24944749
TI  - Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat
      for the NCINI Class of Inhibitors of HIV.
AB  - A scaffold replacement approach was used to identifying the pyridine series of
      noncatalytic site integrase inhibitors. These molecules bind with higher affinity
      to a tetrameric form compared to a dimeric form of integrase. Optimization of the
      C6 and C4 positions revealed that viruses harboring T124 or A124 amino acid
      substitutions are highly susceptible to these inhibitors, but viruses having the
      N124 amino acid substitution are about 100-fold less susceptible. Compound 20 had
      EC50 values <10 nM against viruses having T124 or A124 substitutions in IN and
      >800 nM in viruses having N124 substitions. Compound 20 had an excellent in vitro
      ADME profile and demonstrated reduced contribution of biliary excretion to in
      vivo clearance compared to BI 224436, the lead compound from the quinoline series
      of NCINIs. 

PMID- 24944750
TI  - Discovery of MK-4409, a Novel Oxazole FAAH Inhibitor for the Treatment of
      Inflammatory and Neuropathic Pain.
AB  - We report herein the identification of MK-4409, a potent and selective fatty acid
      amide hydrolase (FAAH) inhibitor. Starting from a high throughput screening (HTS)
      hit, medicinal chemistry efforts focused on optimizing of FAAH inhibition in
      vitro potency, improving the pharmacokinetic (PK) profile, and increasing in vivo
      efficacy in rodent inflammatory and neuropathic pain assays. 

PMID- 24944752
TI  - Are there ways to attenuate arterial calcification and improve cardiovascular
      outcomes in chronic kidney disease?
AB  - The risk of cardiovascular mortality among patients with end-stage renal disease
      is several times higher than general population. Arterial calcification, a marker
      of atherosclerosis and a predictor of cardiovascular mortality, is common in
      chronic kidney disease (CKD). The presence of traditional cardiovascular risk
      factors such as diabetes, hypertension, hyperlipidemia, and advanced age cannot
      fully explain the high prevalence of atherosclerosis and arterial calcification.
      Other factors specific to CKD such as hyperphosphatemia, excess of calcium, high
      dose active vitamin D and prolonged dialysis vintage play important roles in the
      development of arterial calcification. Due to the significant health risk, it is
      prudent to attempt to lower arterial calcification burden in CKD. Treatment of
      hyperlipidemia with statin has failed to lower atherosclerotic and arterial
      calcification burden. Data on diabetes and blood pressure controls as well as
      smoking cessation on cardiovascular outcomes in CKD population are limited.
      Currently available treatment options include non-calcium containing phosphate
      binders, low dose active vitamin D, calcimimetic agent and perhaps
      bisphosphonates, vitamin K and sodium thiosulfate. Preliminary data on
      bisphosphonates, vitamin K and sodium thiosulfate are encouraging but larger
      studies on efficacy and outcomes are needed. 

PMID- 24944753
TI  - Management of hypertension in primary aldosteronism.
AB  - Hypertension causes significant morbidity and mortality worldwide, owing to its
      deleterious effects on the cardiovascular and renal systems. Primary
      hyperaldosteronism (PA) is the most common cause of reversible hypertension,
      affecting 5%-18% of adults with hypertension. PA is estimated to result from
      bilateral adrenal hyperplasia in two-thirds of patients, and from unilateral
      aldosterone-secreting adenoma in approximately one-third. Suspected cases are
      initially screened by measurement of the plasma aldosterone-renin-ratio, and may
      be confirmed by additional noninvasive tests. Localization of aldostosterone
      hypersecretion is then determined by computed tomography imaging, and in
      selective cases with adrenal vein sampling. Solitary adenomas are managed by
      laparoscopic or robotic resection, while bilateral hyperplasia is treated with
      mineralocorticoid antagonists. Biochemical cure following adrenalectomy occurs in
      99% of patients, and hemodynamic improvement is seen in over 90%, prompting a
      reduction in quantity of anti-hypertensive medications in most patients. End
      organ damage secondary to hypertension and excess aldosterone is significantly
      improved by both surgical and medical treatment, as manifested by decreased left
      ventricular hypertrophy, arterial stiffness, and proteinuria, highlighting the
      importance of proper diagnosis and treatment of primary hyperaldosteronism.
      Although numerous independent predictors of resolution of hypertension after
      adrenalectomy for unilateral adenomas have been described, the Aldosteronoma
      Resolution Score is a validated multifactorial model convenient for use in daily
      clinical practice.

PMID- 24944755
TI  - Pediatric hypertension: An update on a burning problem.
AB  - A large number of adults worldwide suffer from essential hypertension, and
      because blood pressures (BPs) tend to remain within the same percentiles
      throughout life, it has been postulated that hypertensive pressures can be
      tracked from childhood to adulthood. Thus, children with higher BPs are more
      likely to become hypertensive adults. These "pre-hypertensive" subjects can be
      identified by measuring arterial BP at a young age, and compared with age, gender
      and height-specific references. The majority of studies report that 1 to 5% of
      children and adolescents are hypertensive, defined as a BP > 95(th) percentile,
      with higher prevalence rates reported for some isolated geographic areas.
      However, the actual prevalence of hypertension in children and adolescents
      remains to be fully elucidated. In addition to these young "pre-hypertensive"
      subjects, there are also children and adolescents with a normal-high BP (90(th)
      95(th) percentile). Early intervention may help prevent the development of
      essential hypertension as they age. An initial attempt should be made to lower
      their BP by non-pharmacologic measures, such as weight reduction, aerobic
      physical exercise, and lowered sodium intake. A pharmacological treatment is
      usually needed should these measures fail to lower BP. The majority of
      antihypertensive drugs are not formulated for pediatric patients, and have thus
      not been investigated in great detail. The purpose of this review is to provide
      an update concerning juvenile hypertension, and highlight recent developments in
      epidemiology, diagnostic methods, and relevant therapies. 

PMID- 24944754
TI  - Anti-hypertensive drugs in children and adolescents.
AB  - Worldwide the prevalence of essential hypertension in children and adolescents
      continues to increase. Traditionally providers have used "off-label" drugs to
      treat pediatric hypertension, meaning that rigorous clinical trials of these
      drugs have not been specifically performed in pediatric patient populations.
      Consequently providers have extrapolated dosing, safety and efficacy from trials
      in adults. This practice is sub-optimal as children demonstrate unique
      differences in drug metabolism and response. Use of unstudied or understudied
      drugs increases risk of adverse events and/or can lead to sub-optimal efficacy.
      Recognizing these concerns, regulatory agencies have created financial incentives
      for industry to conduct pediatric clinical trials. These incentives, coupled with
      the emerging pediatric hypertension epidemic, have spurred over 30 clinical
      trials of anti-hypertensive drugs over the past 15 years and have resulted in
      labeling of 10 new drugs by the United States Food and Drug Administration for
      treatment of hypertension in children and adolescents. Unfortunately the
      financial incentive structures focus on newer drugs and drug classes.
      Consequently there is now a relative dearth of trial data for older but sometimes
      commonly prescribed pediatric antihypertensive drugs. This article reviews recent
      pediatric antihypertensive drug trials with a focus on trial design and
      endpoints, drug dosing, safety, efficacy and specific drug indications. We also
      review the available data and experience for some of the more commonly
      prescribed, but less well studied "older" pediatric antihypertensive drugs. 

PMID- 24944757
TI  - Device-guided breathing exercises for the treatment of hypertension: An overview.
AB  - The American Heart Association considers device-guided breathing as a reasonable
      treatment modality in their statement on non-pharmacological options for lowering
      blood pressure. This review discusses all randomized controlled trials that have
      investigated the effects of device-guided breathing on blood pressure in patients
      with hypertension. Thirteen studies were included in this review. In total, 627
      patients were included, of which 365 patients were allocated to device-guided
      breathing. Only 6 studies used acceptable control groups: listening to music,
      meditative relaxation exercises, or a sham-device. Two sponsored trials showed
      beneficial effects of device-guided breathing, both used listening to music as a
      control group. The remaining 4 studies, which had no employees of the
      manufacturer listed as co-author, observed no beneficial effects on blood
      pressure. There is only 1 study that used a sham device as a control group. All
      other studies were to some extend methodologically flawed. Based on the studies
      with an acceptable methodological quality, there is no clear evidence supporting
      a short-term beneficial effect on blood pressure by using device-guided
      breathing. 

PMID- 24944756
TI  - Potential pathophysiological role for the vitamin D deficiency in essential
      hypertension.
AB  - Vitamin D deficiency has been indicated as a pandemic emerging public health
      problem. In addition to the well-known role on calcium-phosphorus homeostasis in
      the bone, vitamin D-mediated processes have been recently investigated on other
      diseases, such as infections, cancer and cardiovascular diseases. Recently, both
      the discovery of paracrine actions of vitamin D (recognized as "local vitamin D
      system") and the link of vitamin D with renin-angiotensin-aldosterone system and
      the fibroblast growth factor 23/klotho pathways highlighted its active
      cardiovascular activity. Focusing on hypertension, this review summarizes the
      more recent experimental evidence involving the vitamin D system and deficiency
      in the cardiovascular pathophysiology. In particular, we updated the vascular
      synthesis/catabolism of vitamin D and its complex interactions between the
      various endocrine networks involved in the regulation of blood pressure in
      humans. On the other hand, the conflicting results emerged from the comparison
      between observational and interventional studies emphasize the fragmentary nature
      of our knowledge in the field of vitamin D and hypertension, strongly suggesting
      the need of further researches in this field. 

PMID- 24944759
TI  - Asserted and neglected issues linking evidence-based and Chinese medicines for
      cardiac rehabilitation.
AB  - High blood pressure is among the most prevalent chronic disease in adults that
      impacts on the quality of life of patients, which are often subjected to physical
      rehabilitation. Chinese medicine intervention in patients with hypertension
      presents promising albeit inconclusive results, mostly due to methodological
      issues. This paper discusses asserted and neglected issues linking evidence-based
      and Chinese medicines as related to systemic arterial hypertension, as well as
      their impact on the physical rehabilitation of those patients. On the one hand,
      natural history of hypertension, pulse palpation, and herbal therapy are among
      the asserted issues because of the scientific evidence collected about them,
      either in favor or against its integration to the current medical practice. On
      the other hand, anatomical variations of vessels and comparative physiology are
      among the most commonly neglected issues because previous researches on
      integrative medicine ignored the possible effects of these issues as related to
      the study's outcome. The asserted issues highlighted in this paper stimulate the
      increasing use of Chinese medicine for health care and the continuity of research
      on integrative medicine in the cardiovascular field for rehabilitation. The
      neglected issues poses additional challenges that must not be overlooked in
      future research on this topic so that the integration of both traditional and
      current knowledge may be of benefit to the population with cardiovascular
      disease. 

PMID- 24944758
TI  - Hypertension and chronic ethanol consumption: What do we know after a century of
      study?
AB  - The influences of life habits on the cardiovascular system may have important
      implications for public health, as cardiovascular diseases are among the leading
      causes of shorter life expectancy worldwide. A link between excessive ethyl
      alcohol (ethanol) consumption and arterial hypertension was first suggested early
      last century. Since then, this proposition has received considerable attention.
      Support for the concept of ethanol as a cause of hypertension derives from
      several epidemiologic studies demonstrating that in the general population,
      increased blood pressure is significantly correlated with ethanol consumption.
      Although the link between ethanol consumption and hypertension is well
      established, the mechanism through which ethanol increases blood pressure remains
      elusive. Possible mechanisms underlying ethanol-induced hypertension were
      proposed based on clinical and experimental observations. These mechanisms
      include an increase in sympathetic nervous system activity, stimulation of the
      renin-angiotensin-aldosterone system, an increase of intracellular Ca(2+) in
      vascular smooth muscle, increased oxidative stress and endothelial dysfunction.
      The present report reviews the relationship between ethanol intake and
      hypertension and highlights some mechanisms underlying this response. These
      issues are of interest for the public health, as ethanol consumption contributes
      to blood pressure elevation in the population. 

PMID- 24944760
TI  - Alterations in cell adhesion proteins and cardiomyopathy.
AB  - Cell adhesive junction is specialized intercellular structure composed of cell
      adhesion proteins. They are essential to connect adjacent heart muscle cell and
      make heart contraction effectively and properly. Clinical and genetic studies
      have revealed close relationship between cell adhesive proteins and the
      occurrence of various cardiomyopathies. Here we will review recent development on
      the disease phenotype, potential cellular and molecular mechanism related to cell
      adhesion molecules, with particular disease pathogenesis learned from genetic
      manipulated murine models. 

PMID- 24944761
TI  - Autoantibodies to apolipoprotein A-1 as a biomarker of cardiovascular
      autoimmunity.
AB  - Immune-driven inflammation plays an important part in atherogenesis and is
      therefore believed to be key to the development of cardiovascular disease (CVD),
      which is currently the leading cause of death in the Western world. By fulfilling
      some of the Koch postulates, atherogenesis has even been proposed to be
      considered as an autoimmune disease, raising the hope that CVD could be prevented
      by immunomodulation. Nevertheless, the role of the immune system and autoimmune
      reactions in atherosclerosis appear to be a double edged-sword, with both pro
      atherogenic and anti-atherogenic attributes. Hence, if immunomodulation is to
      become a therapeutic option for atherosclerosis and CVD, it will be crucial to
      correctly identify patients who might benefit from targeted suppression of
      deleterious autoimmune responses. This could be achieved, for example, by the
      detection of disease-associated autoantibodies. In this work, we will review the
      currently available clinical, in vitro, and animal studies dedicated to
      autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG), the major proteic
      fraction of high density lipoprotein. Current clinical studies indicate that high
      levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis.
      In addition, in vitro and animal studies indicate a pro-inflammatory and pro
      atherogenic role, supporting the hypothesis that these autoantibodies may play a
      direct causal role in CVD, and furthermore that they could potentially represent
      a therapeutic target for CVD in the future. 

PMID- 24944762
TI  - Elevated blood pressure: Our family's fault? The genetics of essential
      hypertension.
AB  - AIM: To provide an updated review on current genetic aspects possibly affecting
      essential hypertension (EH), and to further elucidate their role in EH. METHODS:
      We searched for genetic and epigenetic factors in major studies associated with
      EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that
      discussed mostly human studies, and were accessible through the university online
      resource. We found 11 genome wide association studies (GWAS), as well as five
      methylation and three miRNA studies that fit our search criteria. A distinction
      was not made between genes with protective effects or negative effects, as this
      article is only meant to be a summary of genes associated with any aspect of EH.
      RESULTS: We found 130 genes from the studies that met our inclusion/exclusion
      criteria. Of note, genes with multiple study references include: STK39, CYP17A1,
      MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3
      TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2,
      PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between
      the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the
      identified genes were found to have functions associated with EH. Many epigenetic
      factors were also correlated with EH. Of the epigenetic factors, there were no
      articles discussing siRNA and its effects on EH that met the search criteria,
      thus the topic was not included in this review. Among the miRNA targets found to
      be associated with EH, many of the genes involved were also identified in the
      GWAS studies. CONCLUSION: Genetic hypertension risk algorithms could be developed
      in the future but may be of limited benefit due to the multi-factorial nature of
      EH. With emerging technologies, like next-generation sequencing, more direct
      causal relationships between genetic and epigenetic factors affecting EH will
      likely be discovered creating a tremendous potential for personalized medicine
      using pharmacogenomics.

PMID- 24944764
TI  - Long-lasting symptoms and diagnostics in a patient with unrecognized right sided
      heart failure: Why listening to the heart is so important.
AB  - M Ebstein is usually diagnosed in early childhood or adolescence. The young woman
      in our case complainted of fatigue and shortness of breath, on physical
      examination she showed signs of heart failure with raised central venous
      pressure, palpable liver, an a cardiac murmer. Based on these findings she should
      have been referred to a cardiologist in an early stage after which transthoracic
      echocardiography resulted in the correct diagnosis. In this case the anomaly was
      missed for many years by different specialists and the patient was treated for
      liver disease, while she was suffering from liver congestion due to right-sided
      heart failure. 

PMID- 24944763
TI  - Heart and lung, a dangerous liaison-Tako-tsubo cardiomyopathy and respiratory
      diseases: A systematic review.
AB  - AIM: To investigate the possible association between Tako-tsubo cardiomyopathy
      (TTC)-a reversible clinical condition mimicking an acute myocardial infarction
      characterized by multifactorial pathophysiologic mechanisms- and respiratory
      system diseases. METHODS: We systematically searched PubMed and EMBASE medical
      information sources, to identify the different triggering causes, limiting our
      search to articles in English. The search keywords were: "tako-tsubo
      cardiomyopathy", "takotsubo", "takotsubo cardiomyopathy", "broken heart
      syndrome", "stress-induced cardiomyopathy", "apical ballooning syndrome", and
      "ampulla cardiomyopathy in combination with respiratory diseases, lung, pulmonary
      disease. For each kind of disease, we registered: author, year and country of
      study, patient sex, age, concurring situation, and outcome. RESULTS: Out of a
      total of 1725 articles found, we selected 37 papers reporting a total of 38
      patients. As expected, most patients were women (81.6%), mean age was 65 +/- 10
      years. Outcome was favorable in 100% of cases, and all the patients have been
      discharged uneventfully in a few days. CONCLUSION: An association between
      respiratory diseases and TTC is likely to exist. Patients with severe respiratory
      diseases, due to the high dosages of beta2-agonists used or to the need of
      invasive procedures, are highly exposed to the risk of developing TTC.

PMID- 24944765
TI  - Unreliability of aortic size index to predict risk of aortic dissection in a
      patient with Turner syndrome.
AB  - Aortic size index (ASI) has been proposed as a reliable criterion to predict risk
      for aortic dissection in Turner syndrome with significant thresholds of 20-25
      mm/m(2). We report a case of aortic arch dissection in a patient with Turner
      syndrome who, from the ASI thresholds proposed, was deemed to be at low risk of
      aortic dissection or rupture and was not eligible for prophylactic surgery. This
      case report strongly supports careful monitoring and surgical evaluation even
      when the ASI is < 20 mm/m(2) if other significant risk factors are present. 

PMID- 24944767
TI  - Estimating free-living human energy expenditure: Practical aspects of the doubly
      labeled water method and its applications.
AB  - The accuracy and noninvasive nature of the doubly labeled water (DLW) method
      makes it ideal for the study of human energy metabolism in free-living
      conditions. However, the DLW method is not always practical in many developing
      and Asian countries because of the high costs of isotopes and equipment for
      isotope analysis as well as the expertise required for analysis. This review
      provides information about the theoretical background and practical aspects of
      the DLW method, including optimal dose, basic protocols of two- and multiple
      point approaches, experimental procedures, and isotopic analysis. We also
      introduce applications of DLW data, such as determining the equations of
      estimated energy requirement and validation studies of energy intake. 

PMID- 24944766
TI  - Diet components can suppress inflammation and reduce cancer risk.
AB  - Epidemiology studies indicate that diet or specific dietary components can reduce
      the risk for cancer, cardiovascular disease and diabetes. An underlying cause of
      these diseases is chronic inflammation. Dietary components that are beneficial
      against disease seem to have multiple mechanisms of action and many also have a
      common mechanism of reducing inflammation, often via the NFkappaB pathway. Thus,
      a plant based diet can contain many components that reduce inflammation and can
      reduce the risk for developing all three of these chronic diseases. We summarize
      dietary components that have been shown to reduce cancer risk and two studies
      that show that dietary walnut can reduce cancer growth and development. Part of
      the mechanism for the anticancer benefit of walnut was by suppressing the
      activation of NFkappaB. In this brief review, we focus on reduction of cancer
      risk by dietary components and the relationship to suppression of inflammation.
      However, it should be remembered that most dietary components have multiple
      beneficial mechanisms of action that can be additive and that suppression of
      chronic inflammation should reduce the risk for all three chronic diseases. 

PMID- 24944768
TI  - Effects of plant-based Korean food extracts on lipopolysaccharide-stimulated
      production of inflammatory mediators in vitro.
AB  - BACKGROUND/OBJECTIVES: The traditional Korean diet is plant-based and rich in
      antioxidants. Previous studies have investigated the potential health benefits of
      individual nutrients of Korean foods. However, the cumulative effects of a Korean
      diet on inflammation remain poorly understood. Therefore, the aim of this study
      was to investigate the anti-inflammatory effects of a plant-based Korean diet.
      MATERIALS/METHODS: Using data from the Fifth Korean National Health and Nutrition
      Examination Survey, 75 individual plant food items were selected which represent
      over 1% of the total diet intake of the Korean diet. These items were classified
      into ten different food groups, and the vegetable (Veg) and fruit (Fruit) groups
      were studied based on their high antioxidant capacity. For comparison, a mixture
      of all ten groups (Mix) was prepared. To produce a model of inflammation with
      which to test these Veg, Fruit, and Mix plant-based Korean food extracts (PKE),
      RAW264.7 macrophages were treated with lipopolysaccharide (LPS). RESULTS: Levels
      of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as protein expression
      of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were found
      to be lower following PKE treatment. Furthermore, PKE treatment was found to
      suppress tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) via the
      nuclear transcription factor kappa-B (NF-kappaB) signaling pathway. Overall, the
      Mix group exhibited the greatest anti-inflammatory effects compared with Veg and
      Fruit PKE group. CONCLUSIONS: Inhibition of LPS-induced pro-inflammatory
      mediators by the PKE tested was found to involve an inhibition of NF-kB
      activation. Moreover, PKE tested have the potential to ameliorate various
      inflammation-related diseases by limiting the excessive production of pro
      inflammatory mediators.

PMID- 24944769
TI  - Anti-carcinogenic effects of non-polar components containing licochalcone A in
      roasted licorice root.
AB  - BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive
      effects. However, glycyrrhizin, a major component in licorice, was found to
      interfere with steroid metabolism and cause edema and hypertension. The roasting
      process of licorice modifies the chemical composition and converts glycyrrhizin
      to glycyrrhetinic acid. The purpose of this study was to examine the anti
      carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to
      identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous
      extracts of roasted and un-roasted licorice were prepared. The active fraction
      was separated from the methylene chloride (MC)-soluble fraction of EERL and the
      structure of the purified compound was determined by nuclear magnetic resonance
      spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone
      A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage
      skin carcinogenesis model. RESULTS: EERL was determined to be more potent and
      efficacious than the ethanol extract of un-roasted licorice in inhibiting the
      growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer
      cells. The aqueous extracts of un-roasted and roasted licorice showed minimal
      effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231
      breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL
      slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and
      CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in
      inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction
      and identified as the active compound of EERL. Both EERL and licochalcone A
      induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin
      papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert
      potent anti-carcinogenic effects, and that roasted rather than un-roasted
      licorice should be favored as a cancer preventive agent, whether being used as an
      additive to food or medicine preparations.

PMID- 24944770
TI  - The anti-inflammatory effect of Indonesian Areca catechu leaf extract in vitro
      and in vivo.
AB  - BACKGROUND/OBJECTIVES: Overproduction of nitric oxide (NO) by the inducible
      nitric oxide synthase (iNOS) enzyme can cause inflammation. Cyclooxygenase-2 (COX
      2) is also involved in the inflammatory response through regulation of nuclear
      factor-kappa B (NF-kappaB). Areca catechu is one of the known fruit plants of the
      Palmaceae family. It has been used for a long time as a source of herbal medicine
      in Indonesia. In this study, we explored the effect of Indonesian Areca catechu
      leaf ethanol extract (ACE) in lipopolysaccharide (LPS)-induced inflammation and
      carrageenan-induced paw edema models. Recently, this natural extract has been in
      the spotlight because of its efficacy and limited or no toxic side effects.
      However, the mechanism underlying its anti-inflammatory effect remains to be
      elucidated. MATERIALS/METHODS: We measured NO production by using the Griess
      reagent, and determined the expression levels of inflammation-related proteins,
      such as iNOS, COX2, and NF-kappaB, by western blot. To confirm the effect of ACE
      in vivo, we used the carrageenan-induced paw edema model. RESULTS: Compared to
      untreated cells, LPS-stimulated RAW 264.7 cells treated with ACE showed reduced
      NO generation and reduced iNOS and COX-2 expression. We found that the acute
      inflammatory response was significantly reduced by ACE in the carrageenan-induced
      paw edema model. CONCLUSION: Taken together, these results suggest that ACE can
      inhibit inflammation and modulate NO generation via downregulation of iNOS levels
      and NF-kappaB signaling in vitro and in vivo. ACE may have a potential medical
      benefit as an anti-inflammation agent.

PMID- 24944771
TI  - Schisandra Chinensis Baillon regulates the gene expression of phase II
      antioxidant/detoxifying enzymes in hepatic damage induced rats.
AB  - BACKGROUND/OBJECTIVES: This study investigated the antioxidant activities and
      hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against
      tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats.
      MATERIALS/METHODS: Sprague-Dawley (SD) rats were pretreated with SCE (300, 600,
      and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each
      animal, except those belonging to the normal control group, were injected with t
      BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP
      injection. RESULTS: Although no significant differences in AST and ALT levels
      were observed among the TC and SCE groups, the high-dose SCE group showed a
      decreasing tendency compared to the TC group. However, erythrocyte SOD activity
      showed a significant increase in the low-dose SCE group compared with the TC
      group. On the other hand, no significant differences in hepatic total glutathione
      (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px)
      activities were observed among the TC and SCE groups. Hepatic histopathological
      evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced
      incidence of lesions, such as neutrophil infiltration, swelling of liver cells,
      and necrosis. In particular, treatment with a high dose of SCE resulted in
      induction of phase II antioxidant/detoxifying enzyme expression, such as
      glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit
      (GCLC). CONCLUSIONS: Based on these results, we conclude that SCE exerts
      protective effects against t-BHP induced oxidative hepatic damage through the
      reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In
      addition, SCE regulates the gene expression of phase II antioxidant/detoxifying
      enzymes independent of hepatic antioxidant enzyme activity.

PMID- 24944772
TI  - Effects of enzymatic hydrolysis of buckwheat protein on antigenicity and
      allergenicity.
AB  - BACKGROUND/OBJECTIVES: Due to its beneficial health effects, use of buckwheat has
      shown a continuous increase, and concerns regarding the allergic property of
      buckwheat have also increased. This study was conducted for evaluation of the
      hydrolytic effects of seven commercial proteases on buckwheat allergens and its
      allergenicity. MATERIALS/METHODS: Extracted buckwheat protein was hydrolyzed by
      seven proteolytic enzymes at individual optimum temperature and pH for four
      hours. Analysis was then performed using SDS-PAGE, immunoblotting, and
      competitive inhibition ELISA (ciELISA) with rabbit antiserum to buckwheat
      protein, and direct ELISA with pooled serum of 21 buckwheat-sensitive patients.
      RESULTS: Alkaline protease, classified as serine peptidase, was most effective in
      reducing allergenicity of buckwheat protein. It caused decomposition of the whole
      buckwheat protein, as shown on SDS-PAGE, and results of immunoblotting showed
      that the rabbit antiserum to buckwheat protein no longer recognized it as an
      antigen. Allergenicity showed a decrease of more than 50% when pooled serum of
      patients was used in ELISA. Two proteolytic enzymes from Aspergillus sp. could
      not hydrolyze buckwheat allergens effectively, and the allergenicity even
      appeared to increase. CONCLUSIONS: Serine-type peptidases appeared to show a
      relatively effective reduction of buckwheat allergenicity. However, the
      antigenicity measured using rabbit antiserum did not correspond to the
      allergenicity measured using sera from human patients. Production of less
      allergenic buckwheat protein may be possible using enzymatic hydrolysis.

PMID- 24944773
TI  - Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats
      with diet-induced atherosclerosis.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to investigate the effects of
      exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging
      model rats with diet-induced atherosclerosis. MATERIALS/METHODS: Forty-eight male
      Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging
      control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF
      EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and
      atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats
      were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose
      of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical
      and immunohistochemical analyses. REULTS: The EX and KRG supplementation
      significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of
      HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group
      showed a decreased plasma CRP and increase plasma NO activities compared to AHF
      group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-alpha, IL-6,
      COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta. CONCLUSION:
      These results suggest that EX alone, KRG alone, and combined treatment of EX and
      KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis,
      possibly acting via the decreased of CRP and pro-inflammation proteins and the
      increased NO and eNOS.

PMID- 24944774
TI  - Effect of St. John's Wort (Hypericum perforatum) on obesity, lipid metabolism and
      uterine epithelial proliferation in ovariectomized rats.
AB  - BACKGROUND/OBJECTIVES: This study was conducted to assess the potential of St.
      John's Wort (Hypericum perforatum) to prevent obesity and abnormalities in lipid
      metabolism induced by ovariectomy in a rat model without stimulatory activity on
      uterus. MATERIALS/METHODS: Ovariectomized (OVX) rats were treated for 6 weeks
      with 70% ethanol extracts of Hypericum perforatum [HPEs: whole plant (WHPE) and
      flower and leaves (FLHPE)], beta-estradiol-3-benzoate at a dose of 50 ug/kg/day
      (E2) or vehicle (distilled water). RESULTS: As expected, OVX increased body
      weight gain and adiposity and showed higher food efficacy ratio. OVX also
      increased the serum cholesterol as well as insulin resistance, while reducing
      uterus weight and uterine epithelial proliferation rate. HPEs (WHPE and FLHPE)
      showed estrogen-like effect on body weight gain, adipose tissue weight and food
      efficacy ratio in OVX rats. HPEs prevented hypercholesterolemia induced by OVX
      more effectively than E2. E2 increased uterus weight and epithelial proliferation
      rate in OVX rats, while HPEs maintained them at the level of the sham-operated
      animals. CONCLUSIONS: Our finding demonstrates that HPEs can be considered as an
      effective agent to prevent OVX-induced obesity without stimulatory activity on
      uterus.

PMID- 24944775
TI  - Stages of change to increase fruit and vegetable intake and its relationships
      with fruit and vegetable intake and related psychosocial factors.
AB  - BACKGROUND/OBJECTIVES: Understanding individual's intention, action and
      maintenance to increase fruit and vegetable intake is an initial step in
      designing nutrition or health promotion programs. This study aimed to determine
      stages of change to increase fruit and vegetable intake and its relationships
      with fruit and vegetable intake, self-efficacy, perceived benefits and perceived
      barriers. SUBJECTS/METHODS: This cross-sectional study was conducted among 348
      public university staff in Universiti Putra Malaysia. A pre-tested self
      administered questionnaire and two days 24-hour diet recall were used. RESULTS:
      Half of the respondents (50%) were in preparation stage, followed by 43% in
      action/maintenance, 7% in pre-contemplation/contemplation stages. Respondents in
      action/maintenance stages had significantly higher self-efficacy (F = 9.17, P <
      0.001) and perceived benefits (F = 5.07, P < 0.01) while respondents in pre
      contemplation/contemplation and preparation stages had significantly higher
      perceived barriers (F = 4.83, P < 0.05). Perceived benefits tend to outweigh
      perceived barriers pre-ceding to taking action. Self-efficacy is important in
      motivating individuals to increase fruit and vegetable intake as self-efficacy
      and perceived barriers crossed over between preparation and action/maintenance.
      Respondents in action/maintenance stages had the highest adjusted mean serving of
      fruit and vegetable intake (F = 4.52, P < 0.05) but the intake did not meet
      recommendation. CONCLUSION: Intervention strategies should emphasize on
      increasing perceived benefits and building self-efficacy by providing knowledge
      and skills to consume a diet high in fruits and vegetables in order to promote
      healthy changes in having high fruit and vegetable intake.

PMID- 24944776
TI  - Association between household food insecurity and nutritional outcomes among
      children in Northeastern of Peninsular Malaysia.
AB  - BACKGROUND/OBJECTIVES: The purpose of the study was to investigate the
      relationship between household food insecurity and nutritional status of children
      in low-income households. A cross sectional study involved a survey of households
      (n = 223) receiving the financial assistance. SUBJECTS/METHODS: Eligible mothers
      that fulfilled the inclusion criteria such as non-pregnant, non-lactating
      mothers, aged 18 to 55 years with their youngest children aged 2 to 12 years,
      were purposively selected. The Radimer/Cornell hunger and food-insecurity
      instrument was administered and children's height and weight were measured.
      RESULTS: About 16.1% of the households were food secure, while 83.9% experienced
      some kind of food insecurity. Out of food insecure category, 29.6% households
      were food insecure, 19.3% women were individual food insecure and 35.0% fell into
      the child hunger category. Education of the mother (P = 0.047), household size (P
      = 0.024), number of children (P = 0.024), number of children going to school (P =
      0.048), total monthly income (P < 0.001), income per capital (P < 0.001), number
      of household members contributing to the income (P = 0.018) and food expenditure
      (P = 0.006) were significant risk factors for household food insecurity. The
      prevalence of underweight, stunting and wasting in children were 61.0%, 61.4% and
      30.6% respectively. Based on multinomial logistic regression, children in food
      insecure households were 2.15 times more likely to be underweight and three times
      to be stunted than children in the food-secure households. CONCLUSIONS: The
      findings suggest that household food insecurity is associated with the
      nutritional status of the children in the rural area of Northeastern Peninsular
      Malaysia.

PMID- 24944777
TI  - Structural relations in the effect of convenience food satisfaction and quality
      of life according to dietary style: Comparative study of singles in metropolitan
      area of Korea, Japan and China.
AB  - BACKGROUND/OBJECTIVES: Due to recent changes in social structure, single-person
      households are on the rise worldwide and therefore the interest in the quality of
      life of singles is increasing, but the research on the relationships related to
      their diet-related quality of life is scarce. This research analyzes the
      structural relations in the effect of convenience food satisfaction and quality
      of life according to dietary style of Korean, Japanese and Chinese singles.
      SUBJECTS/METHODS: The targets of this study were Korean, Japanese, and Chinese
      singles, identified as adults between the ages of 25 and 54, having economic
      capabilities or working and living alone, either legally or in actuality having
      no partner. A statistical analysis was conducted using SPSS12.0 for Windows and
      SEM using AMOS 5.0 statistics package. The reliability of these findings was
      supported by a Cronbach's alpha coefficient of 0.6 and higher for all the
      factors. In an attempt to study the level of satisfaction with convenience food
      in accordance to dietary style and the quality of life of singles, a structural
      equation model was constructed and analyzed. RESULTS: Of the three countries,
      regarding the effect of dietary style on singles' quality of life, the
      convenience-oriented style was found to have a negative effect on Korean singles'
      overall quality of life, but a positive effect on Japanese singles' overall
      quality of life, and a negative effect on Chinese singles' positive psychological
      aspect of quality of life. In addition, although Chinese singles have a high
      level of interest in health, they have an overall high level of satisfaction
      regarding fast food and its nutritional value. CONCLUSIONS: The number of singles
      in Korea, Japan, and China has been consistently increasing in recent years, and
      there is a need for continuous interest in their healthy dietary lifestyles in
      terms of convenience, economy, and taste.

PMID- 24944778
TI  - Dietary changes in Vietnamese marriage immigrant women: The KoGES follow-up
      study.
AB  - BACKGROUND/OBJECTIVES: The immigrant population has grown considerably in South
      Korea since the early 1990s due to international marriages. Dietary changes in
      immigrants are an important issue, because they are related to health and disease
      patterns. This study was conducted to compare changes in dietary intake between
      baseline and follow-up periods. SUBJECTS/METHODS: Two hundreds thirty three
      Vietnamese female married immigrants. Baseline data were collected during 2006
      2009, and the follow-up data were collected during 2008 and 2010. Food
      consumption was assessed using a 1-day 24-hour recall. RESULTS: The amount of the
      total food consumed (P < 0.001) including that of cereals (P = 0.004), vegetables
      (P = 0.003), and fruits (P = 0.002) decreased at follow-up compared to that at
      baseline, whereas consumption of milk and dairy products increased (P = 0.004).
      Accordingly, the overall energy and nutrient intake decreased at follow-up,
      including carbohydrates (P = 0.012), protein (P = 0.021), fiber (P = 0.008), iron
      (P = 0.009), zinc (P = 0.006), and folate (P = 0.002). Among various
      anthropometric and biochemical variables, mean skeletal muscle mass decreased (P
      = 0.012), plasma high density lipoprotein-cholesterol increased, (P = 0.020) and
      high sensitivity C-reactive protein decreased at follow-up (P < 0.001).
      CONCLUSIONS: A long-term follow-up study is needed to investigate the association
      between changes in food and nutrient intake and anthropometric and biochemical
      variables in these Vietnamese female marriage immigrants.

PMID- 24944779
TI  - Using the theory of planned behavior to determine factors influencing processed
      foods consumption behavior.
AB  - BACKGROUND/OBJECTIVES: The purpose of this study is to identify how level of
      information affected intention, using the Theory of Planned Behavior.
      SUBJECTS/METHODS: The study was conducted survey in diverse community centers and
      shopping malls in Seoul, which yielded N = 209 datasets. To compare processed
      foods consumption behavior, we divided samples into two groups based on level of
      information about food additives (whether respondents felt that information on
      food additives was sufficient or not). We analyzed differences in attitudes
      toward food additives and toward purchasing processed foods, subjective norms,
      perceived behavioral control, and behavioral intentions to processed foods
      between sufficient information group and lack information group. RESULTS: The
      results confirmed that more than 78% of respondents thought information on food
      additives was insufficient. However, the group who felt information was
      sufficient had more positive attitudes about consuming processed foods and
      behavioral intentions than the group who thought information was inadequate. This
      study found people who consider that they have sufficient information on food
      additives tend to have more positive attitudes toward processed foods and
      intention to consume processed foods. CONCLUSIONS: This study suggests increasing
      needs for nutrition education on the appropriate use of processed foods.
      Designing useful nutrition education requires a good understanding of factors
      which influence on processed foods consumption.

PMID- 24944780
TI  - Cheese consumption in relation to cardiovascular risk factors among Iranian
      adults- IHHP Study.
AB  - BACKGROUND/OBJECTIVE: It is expected that dairy products such as cheeses, which
      are the main source of cholesterol and saturated fat, may lead to the development
      or increase the risk of cardiovascular and metabolic diseases; however, the
      results of different studies are inconsistent. This study was conducted to assess
      the association between cheese consumption and cardiovascular risk factors in an
      Iranian adult population. SUBJECTS/METHODS: Information from the Isfahan Healthy
      Heart Program (IHHP) was used for this cross-sectional study with a total of
      1,752 participants (782 men and 970 women). Weight, height, waist and hip
      circumference measurement, as well as fasting blood samples were gathered and
      biochemical assessments were done. To evaluate the dietary intakes of
      participants a validated food frequency questionnaire, consists of 49 items, was
      completed by expert technicians. Consumption of cheese was classified as less
      than 7 times per week and 7-14 times per week. RESULTS: Higher consumption of
      cheese was associated with higher C-Reactive Protein (CRP), apolipoprotein A and
      high density lipoprotein cholesterol (HDL-C) level but not with fasting blood
      sugar (FBS), total cholesterol, low density lipoprotein cholesterol (LDL-C),
      triglyceride (TG) and apolipoprotein B. Higher consumption of cheese was
      positively associated with consumption of liquid and solid oil, grain, pulses,
      fruit, vegetable, meat and dairy, and negatively associated with Global Dietary
      Index. After control for other potential confounders the association between
      cheese intake and metabolic syndrome (OR: 0.81; 96%CI: 0.71-0.94), low HDL-C
      level (OR: 0.87; 96%CI: 0.79-0.96) and dyslipidemia (OR: 0.88; 96%CI: 0.79-0.98)
      became negatively significant. CONCLUSION: This study found an inverse
      association between the frequency of cheese intake and cardiovascular risk
      factors; however, further prospective studies are required to confirm the present
      results and to illustrate its mechanisms.

PMID- 24944781
TI  - An ontological modeling approach for abnormal states and its application in the
      medical domain.
AB  - BACKGROUND: Recently, exchanging data and information has become a significant
      challenge in medicine. Such data include abnormal states. Establishing a unified
      representation framework of abnormal states can be a difficult task because of
      the diverse and heterogeneous nature of these states. Furthermore, in the
      definition of diseases found in several textbooks or dictionaries, abnormal
      states are not directly associated with the corresponding quantitative values of
      clinical test data, making the processing of such data by computers difficult.
      RESULTS: We focused on abnormal states in the definition of diseases and proposed
      a unified form to describe an abnormal state as a "property," which can be
      decomposed into an "attribute" and a "value" in a qualitative representation. We
      have developed a three-layer ontological model of abnormal states from the
      generic to disease-specific level. By developing an is-a hierarchy and combining
      causal chains of diseases, 21,000 abnormal states from 6000 diseases have been
      captured as generic causal relations and commonalities have been found among
      diseases across 13 medical departments. CONCLUSIONS: Our results showed that our
      representation framework promotes interoperability and flexibility of the
      quantitative raw data, qualitative information, and generic/conceptual knowledge
      of abnormal states. In addition, the results showed that our ontological model
      have found commonalities in abnormal states among diseases across 13 medical
      departments.

PMID- 24944782
TI  - The sperm's tale.

PMID- 24944783
TI  - Systematic conversion to generic tacrolimus in stable kidney transplant
      recipients.
AB  - BACKGROUND: Tacrolimus (Prograf(r)) is a key drug in the immunosuppressive
      treatment of renal transplant patients. Since the expiration of the patent for
      Prograf(r), generic preparations have been approved in Europe as bioequivalence
      has been shown in healthy volunteers. However, few studies have investigated
      whether patients can be successfully converted from Prograf(r) to generic
      tacrolimus. Tacrolimus drug costs are by far the largest single item in the total
      drug expenditure for patients with renal disease in the Stockholm area.
      Considerable reductions in drug costs could be achieved if generic tacrolimus
      were to be used. The aim of this quality assurance study was to evaluate whether
      a switch from Prograf(r) to generic tacrolimus (Tacrolimus Sandoz(r)) could be
      safely performed in renal transplant patients. It further aimed to investigate
      changes of renal function (measured in estimated glomerular filtration rate,
      eGFR), need for dose changes and to calculate potential drug cost savings as a
      result of the conversion. METHODS: We planned to recruit at least 50 patients.
      Plasma creatinine levels and trough concentrations of tacrolimus were collected
      from patients with renal transplants at three occasions during treatment with
      Prograf(r) and three times after conversion to Tacrolimus Sandoz(r). The eGFR was
      calculated before and after the conversion. RESULTS: Sixty-three of 67 enrolled
      patients (69% males, age 28-80 years) are included in this analysis. The ratio of
      mean trough concentrations of tacrolimus after comparison with before conversion
      was 1.02 (90% confidence interval 0.95-1.09). Fourteen patients experienced a
      change in tacrolimus levels >20% compared with baseline, no patients changed >20%
      in eGFR. The drug cost saving per daily dose was 33.40 SEK (~?3.60, -23%).
      CONCLUSIONS: Stable kidney transplant patients treated with Prograf(r) can be
      converted to Tacrolimus Sandoz(r) if trough concentrations of tacrolimus and
      plasma creatinine levels are closely monitored. The conversion brought savings,
      despite costs for extra monitoring.

PMID- 24944785
TI  - Acute oxalate nephropathy induced by oral high-dose vitamin C alternative
      treatment.

PMID- 24944784
TI  - Genetic testing can resolve diagnostic confusion in Alport syndrome.
AB  - Alport syndrome (AS) is a familial glomerular disorder resulting from mutations
      in the genes encoding several members of the type IV collagen protein family.
      Despite advances in molecular genetics, renal biopsy remains an important initial
      diagnostic tool. Histological diagnosis is challenging as features may be non
      specific, particularly early in the disease course and in females with X-linked
      disease. We present three families for whom there was difficulty in correctly
      diagnosing AS or thin basement membrane nephropathy as a result of
      misinterpretation of non-specific and incomplete histology. We highlight the
      importance of electron microscopy and immunofluorescence in improving diagnostic
      yield and also the hazard of interpreting a descriptive histological term as a
      diagnostic label. Molecular genetic testing allows a definitive diagnosis to be
      made in index patients and at-risk family members.

PMID- 24944786
TI  - Atypical haemolytic uraemic syndrome associated with a CD46 mutation triggered by
      Shigella flexneri.
AB  - We present a case of haemolytic uraemic syndrome (HUS) triggered by Shigella
      flexneri. Of the Shigella species, only S. dysenteriae type 1 is said to produce
      Shiga toxin and consequently cause HUS. Investigation of the complement system in
      this patient revealed a CD46 mutation. In individuals with mutations in
      complement genes incomplete penetrance of atypical HUS (aHUS) is seen, suggesting
      that a trigger, such as infection, is required for disease to manifest. In an era
      of complement modulatory therapy for aHUS it is important to be alert to unusual
      presentations of diarrhoeal-associated disease.

PMID- 24944787
TI  - Pneumocafe project: an inquiry on current COPD diagnosis and management among
      General Practitioners in Italy through a novel tool for professional education.
AB  - BACKGROUND: Symptoms of COPD are frequently disregarded by patients and also by
      general practitioners (GPs) in early stages of the disease, that consequently is
      diagnosed when already at an advanced grade of severity. Underdiagnosis and
      undertreatment of COPD and scarce use of spirometry are widely recurrent, while a
      better knowledge of the disease and a wider use of spirometry would be critical
      to diagnose more patients still neglected, do it at an earlier stage and properly
      treat established COPD. The aim of Pneumocafe project is to improve, through an
      innovative approach, the diagnosis and management of COPD at primary care level
      increasing the awareness of issues pertaining to early diagnosis, adequate
      prevention and correct treatment of the disease. METHODS: Pneumocafe is based on
      informal meetings between GPs of various geographical zones of Italy and their
      reference respiratory specialist (RS), aimed at discussing the current practice
      in comparison to suggestions of official guidelines, analyzing the actual
      problems in diagnosing and managing COPD patients and sharing the possible
      solution at the community level. In these meetings RSs faced many issues
      including patho-physiological mechanisms of bronchial obstruction, significance
      of clinical symptoms, patients' phenotyping, and clinical approach to diagnosis
      and long-term treatment, also reinforcing the importance of a timely diagnosis,
      proper long term treatment and the compliance to treatment. At the end of each
      meeting GPs had to fill in a questionnaire arranged by the scientific board of
      the Project that included 18 multiple-choice questions concerning their approach
      to COPD management. The results of the analysis of these questionnaires are here
      presented. RESULTS: 1, 964 questionnaires were returned from 49 RSs. 1,864
      questionnaires out of those received (94.91% of the total) resulted properly
      compiled and form the object of the present analysis. The 49 RSs, 37 males and 12
      females, were distributed all over the Italian country and practiced their
      profession both in public and private hospitals and in territorial sanitary
      facilities. GPs were 1,330 males (71.35%) and 534 females (28.64%), mean age
      56,29 years (range 27-70 yrs). Mean duration of general practice was 25.56 years
      (range: 0,5-40 yrs) with a mean of 1,302.43 patients assisted by each GP and
      2,427,741 patients assisted in all. The majority of GPs affirmed that in their
      patients COPD has a mean-to-great prevalence and a mean/high impact on their
      practice, preceded only by diabetes and heart failure. Three-quarters of GPs
      refer to COPD guidelines and most of them believe that a screening on their
      assisted patients at risk would enhance early diagnosis of COPD. Tobacco smoking
      is the main recognized cause of COPD but the actions carried out by GPs to help a
      patient to give up smoking result still insufficient. The majority of GPs
      recognize spirometry as necessary to early COPD diagnosis, but the main obstacle
      pointed out to its wider use was the too long time for the spirometry to be
      performed. GPs' main reason for prescribing a bronchodilator is dyspnea and
      bronchodilators preferably prescribed are LABA and LAMA. Control of patient's
      adherence to therapy is mainly carried out by GPs checking the number of drugs
      annually prescribed or asking the patient during a control visit. Finally, about
      how many COPD patients GPs believe are in their group of assisted patients, a
      mean range of 25-40 patients was reported, that is consistently below the
      forecast based on epidemiological data and number of patients assisted by each
      GP. CONCLUSIONS: The results obtained with this project confirm the validity of
      this informal approach to professional education. Furthermore, this inquiry
      provided important insights about the general management of COPD and the process
      of integration between RS and GPs activities on this disease condition in the
      long run.

PMID- 24944788
TI  - Betatrophin provides a new insight into diabetes treatment and lipid metabolism
      (Review).
AB  - Replenishing the insulin-producing beta-cell mass is considered to be a potential
      cure for diabetes. A recent study identified a secreted protein, known as
      betatrophin, which potently induces pancreatic beta-cell proliferation. Notably,
      a number of studies reportedly identified betatrophin, which is also known as
      lipasin, atypical angiopoietin-like 8 and refeeding-induced fat and liver
      protein, and considered to be a novel regulator in lipid metabolism according to
      the studies. The identification of betatrophin was considered to create novel
      opportunities for potential diabetes therapy. In the present study, the current
      knowledge of betatrophin is reviewed, with regards to its character and function
      in lipid homeostasis and pancreatic beta-cell proliferation.

PMID- 24944789
TI  - Nucleotide excision repair gene polymorphisms and prognosis of non-small cell
      lung cancer patients receiving platinum-based chemotherapy: A meta-analysis based
      on 44 studies.
AB  - : Genetic variations are linked to DNA repair ability and varied drug metabolism
      that largely affects the prognosis of antineoplastic agents, including platinum.
      The purpose of the present meta-analysis was to determine the roles of the
      genetic variants of the nucleotide excision repair genes on the prognosis of
      platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC).
      A meta-analysis was performed, including 44 original studies with a total number
      of 5,944 patients with NSCLC according to the search strategy. The tumor
      responses [complete response, partial response, stable disease (SD) and
      progressive disease (PD)] were estimated and the Stata package was used for the
      comprehensive quantitative analyses. The results showed that the XPG C46T
      polymorphism was significantly associated with tumor chemotherapy when SD or PD
      was considered as a non-response [TT vs. CC: risk ratio (RR), 1.31; 95%
      confidence interval (CI), 1.14-1.5; and P=0.00; TT/CT vs. CC: RR, 1.23; 95% CI,
      1.11-1.36; and P=0.00; and TT vs. CC/CT: RR, 1.22; 95% CI, 1.11-1.36; and
      P=0.00]. No significant association between the ERCC1 C118T/C8092A XPDLys751Gln
      and XPA A23G polymorphisms and tumor response was found. There was also no
      evidence found to support the use of the ERCC1 C118T/C8092A XPDLys751Gln and XPA
      A23G polymorphisms as prognostic predictors of platinum-based chemotherapies in
      NSCLC in the meta-analysis. For the XPG C46T polymorphisms, a significant
      association with an objective response was detected. Multiple and large-scale
      studies are required to further investigate the association between biomarkers
      and tumor prognosis.

PMID- 24944790
TI  - Screening for 392 polymorphisms in 141 pharmacogenes.
AB  - Pharmacogenomics is the study of the association between inter-individual genetic
      differences and drug responses. Researches in pharmacogenomics have been
      performed in compliance with the use of several genotyping technologies. In this
      study, a total of 392 single-nucleotide polymorphisms (SNPs) located in 141
      pharmacogenes, including 21 phase I, 13 phase II, 18 transporter and 5 modifier
      genes, were selected and genotyped in 150 subjects using the GoldenGate assay or
      the SNaPshot technique. These variants were in Hardy-Weinberg equilibrium (HWE)
      (P>0.05), except for 22 SNPs. Genotyping of the 392 SNPs revealed that the minor
      allele frequencies of 47 SNPs were <0.05, 105 SNPs were monomorphic and 22
      variants were not in HWE. Also, based on previous studies, we predicted the
      association between the polymorphisms of certain pharmacogenes, such as
      cytochrome P450 2D6, cytochrome P450 2C9, vitamin K epoxide reductase complex,
      subunit 1, cytochrome P450 2C19, human leukocyte antigen, class I, B and
      thiopurine S-methyltransferase, and drug efficacy. In conclusion, our study
      demonstrated the allele distribution of SNPs in 141 pharmacogenes as determined
      by high-throughput screening. Our results may be helpful in developing
      personalized medicines by using pharmacogene polymorphisms.

PMID- 24944791
TI  - Comparison of polymerase chain reaction ribotyping, toxinotyping and nutritional
      aspects of toxin production of Clostridium difficile strains.
AB  - Clostridium difficile (C. difficile) is the leading cause of infectious diarrhea
      in hospitals worldwide. Enterotoxin A (TcdA) and cytotoxin B (TcdB), have been
      identified as the main virulence factors of C. difficile. In China, data on
      polymerase chain reaction (PCR) ribotypes and abilities of hospital-derived C.
      difficile isolates to produce TcdA and TcdB are sparse. In this study, we
      identified 40 C. difficile isolates from the Taizhou hospital and investigated
      their PCR ribotypes based on the 16S-23S rRNA gene intergenic spacer region. The
      ability of different ribotypes to produce TcdA and TcdB was determined by
      immunochromatography and cytotoxicity assays, respectively. The effects of the
      nutritional status on the production of these toxins were also investigated.

PMID- 24944792
TI  - Differential expression of CRKL and AXL genes in lung adenocarcinoma subtypes
      according to the epidermal growth factor receptor and anaplastic lymphoma kinase
      gene status.
AB  - Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related
      mortality. Adenocarcinoma (AC) is the predominant histological type of NSCLC;
      however, AC consists of several subtypes. It has not yet been determined whether
      there is a correlation of CRKL and AXL expression with epidermal growth factor
      receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene status in lung AC. We
      assayed exons 18 through 21 of the EGFR gene by direct sequencing; ALK
      rearrangement and the expression of CRKL and AXL were detected by immunostaining.
      A total of 212 cases of AC were included in this study, diagnosed using the novel
      classification system established by the International Association for the Study
      of Lung Cancer, the American Thoracic Society and the European Respiratory
      Society in 2011, including 69 acinar ACs, 17 lepidic predominant ACs (LPAs), 63
      papillary, 14 mucinous, 17 micropapillary and 32 solid ACs. Of the 212 cases, 101
      harbored EGFR mutations. The most common subtypes carrying delK745-S753 were
      papillary and acinar ACs. ALK rearrangement was found in 23 cases (11%) of lung
      ACs. Acinar and solid ACs were the most frequent subtypes with ALK aberrance,
      particularly in acinar ACs with cribriform structure (4/5 cases, 80%). The
      expression of CRKL was significantly different among the AC subtypes (P=0.01),
      with the highest and lowest expression levels of CRKL protein in papillary ACs
      and LPAs, respectively (P<0.05). AXL expression was also significantly different
      among the AC subtypes (P=0.002) and was correlated with lymph node infiltration
      in acinar ACs. ACs with EGFR mutations exhibited high levels of AXL protein
      expression compared to those without mutations (P<0.001). Acinar AC with
      cribriform structure is a distinct subtype that frequently harbors ALK
      rearrangement. The activation of AXL may be one of the factors contributing to
      the invasion of acinar and micropapillary ACs.

PMID- 24944793
TI  - Effect of benazepril on the transdifferentiation of renal tubular epithelial
      cells from diabetic rats.
AB  - The aim of this study was to investigate the effect of benazepril on the
      transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty
      male Sprague-Dawley rats were included in the present study. Eight of the 30 rats
      were randomly selected and served as the normal control group (N group), while
      the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic
      rat model. Rats with diabetes were randomly divided into the diabetic (DM group)
      and benazepril (B group) groups. The total course was conducted over 12 weeks.
      Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum
      creatinine and blood urea nitrogen were measured at the start and end of the
      study. We observed the tubulointerstitial pathological changes, and applied
      immunohistochemistry and western blotting to detect the expression of alpha
      smooth muscle actin (alpha-SMA) in renal tissue. The levels of blood glucose,
      kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen
      and tubulointerstitial damage index (TII) in the DM group were significantly
      higher than that in the N group (p<0.01). Except for blood glucose and
      kidney/body weight, the remaining indices were lower in the B group compared with
      those in the DM group (p<0.01). Immunohistochemical staining results revealed the
      expression of alpha-SMA in renal tubular epithelial cells to be significantly
      higher in the DM and B groups compared with the control (N) group (p<0.01).
      Western blot analysis revealed that the expression of alpha-SMA in diabetic renal
      tissue increased 3.27-fold compared with that of the N group, while the
      expression of alpha-SMA in the B group decreased 45% compared with that in the DM
      group. In conclusion, benazepril significantly reduced the expression of alpha
      SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the
      transdifferentiation of renal tubular epithelial cells and played an important
      role in kidney protection.

PMID- 24944794
TI  - A U87-EGFRvIII cell-specific aptamer mediates small interfering RNA delivery.
AB  - U87-EGFRvIII is a U87 glioma cell line that overexpresses epidermal growth factor
      receptor variant III (EGFRvIII). In the present study, we investigated whether a
      DNA aptamer selected against U87-EGFRvIII using cell-based systematic evolution
      of ligands by exponential enrichment (cell-SELEX) could deliver c-Met small
      interfering RNA (siRNA) into U87-EGFRvIII cells and silence the targeted gene
      expression. The selected biotinylated aptamer (BA) was coupled to biotinylated c
      Met siRNA by streptavidin to deliver siRNA into U87-EGFRvIII cells. c-Met siRNA,
      transfected with lipofectamine 2000, served as a positive control, while control
      siRNA, transferred with BA, served as a negative control. Western blotting was
      performed to detect changes in the c-Met protein expression, and MTT and Annexin
      V-fluorescein isothiocyanate/propidium iodine assays were used to determine
      changes in the proliferation and apoptosis of U87-EGFRvIII cells, respectively.
      Similar to the liposome-mediated group, U87-EGFRvIII cells that were transfected
      with BA-c-Met siRNA experienced a significant decrease in the c-Met protein
      expression (P<0.05). There were also significant increases in the apoptotic rate
      (P<0.05) and inhibition rate of cell growth (P<0.01) compared with the negative
      control group, indicating that BA could deliver c-Met siRNA into U87-EGFRvIII and
      result in target gene silencing. In conclusion, the results demonstrated that
      this DNA aptamer, obtained through cell-SELEX, can be used as an efficient and
      targeted carrier for siRNA delivery, providing a novel approach and strategy for
      the targeted combination therapy of glioblastoma.

PMID- 24944795
TI  - Tanshinone IIA promotes non-amyloidogenic processing of amyloid precursor protein
      in platelets via estrogen receptor signaling to phosphatidylinositol 3
      kinase/Akt.
AB  - Amyloid beta peptide (Abeta) is a proteolytic product of amyloid precursor
      protein (APP). Recent findings suggested that platelet-derived Abeta is closely
      associated with the pathogenesis of atherosclerosis (AS). Tanshinone IIA (Tan
      IIA), a pharmacologically active component of the Chinese herb Salvia
      miltiorrhiza Bunge, has long been used to treat AS and was also identified as a
      phytoestrogen. However, it has not been elucidated whether Tan IIA intervenes
      with platelet APP processing and whether such an intervention is associated with
      its estrogenic activity. Using human platelets, this study demonstrated that Tan
      IIA promoted the non-amyloidogenic cleavage of APP via estrogenic activity. The
      phosphatidylinositol 3-kinase/Akt pathway may be involved in this effect of Tan
      IIA on platelet APP metabolism as a downstream effector of estrogen receptor
      signaling. This study aimed to extend the existing data and provide new insights
      into the mechanism underlying the vasoprotective effect of Tan IIA.

PMID- 24944796
TI  - Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes
      for colorectal cancer patients.
AB  - Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells
      are under constant scrutiny, with the aim to design an effective and reduced
      toxicity therapy, which will benefit patients via improved quality of life and
      improved prognosis. Four patients with stage IV colon cancer were administered 1,
      3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood
      was collected from the patients and the ex vivo activation and expansion of NK
      and T cells was performed in Good Manufacturing Practice-certified clean rooms
      for ~12-15 days. Immunophenotypic analysis of the peripheral blood mononuclear
      cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and
      the patients were followed up. On average, 4.8*107 initial PBMCs and 2.7*109
      total expanded cells were obtained. The intravenous infusions of the expanded
      cells were not accompanied by adverse reactions. Improved prognosis, reflected by
      a considerable decrease in the cancer markers, accompanied by an improved quality
      of life in the patients were observed. In conclusion, potential strategies are
      currently under development for the large-scale production of effectors cells;
      therefore, autologous immune enhancement therapy (AIET) may be considered as a
      viable approach to cancer treatment.

PMID- 24944797
TI  - Tiny masking locked nucleic acids effectively bind to mRNA and inhibit binding of
      microRNAs in relation to thermodynamic stability.
AB  - MicroRNA (miRNA) therapeutics, whereby miRNA networks are modified to treat
      disease, is attracting considerable attention in the field of nucleic acid
      therapeutics. In this study, we described highly effective constructs of miRNA
      masking oligonucleotides (ONDs) that bind to mRNA and interfere with the binding
      of miRNA to its target site. Moreover, the correlation between ONDs and
      thermodynamics on the effect of masking mRNA was investigated. Using a reporter
      system, we evaluated ONDs of various lengths that have been linked to O-methyl
      groups and/or locked nucleic acids (LNAs) on their ability to inhibit binding of
      miRNA to target mRNA in cultured cells. LNAs of 10-12 nucleotides (nt) exerted
      the strongest inhibitory effects, which were similar to the inhibitory activity
      of antisense ONDs against miRNA. No such inhibitory activity was observed with
      the standard 22-nt O-methyl-modified RNA in the reporter system. The results of
      melting temperature experiments combined with the masking activity that prevented
      binding of miRNA to its target, suggested that a major contributor to the masking
      activity in cells may be the thermodynamic properties of the complexes. Our
      findings may contribute to the design of effective masking LNAs.

PMID- 24944798
TI  - Effect of cytochalasin B on 3-O-[14C]-methyl-D-glucose or D-[U-14C]glucose
      handling by BRIN-BD11 cells.
AB  - The present study aimed to investigate the effects of cytochalasin B (20 MUM) on
      the uptake of 3-O-[14C]-methyl-D-glucose or D-[U-14C]glucose (8.3 mM each) by
      BRIN-BD11 cells. Taking into account the distribution space of tritiated water
      (3HOH), which was unexpectedly increased shortly after exposure of the cells to
      cytochalasin B and then progressively returned to its control values, and that of
      L-[1-14C]glucose, used as an extracellular marker, it was demonstrated that
      cytochalasin B caused a modest, but significant inhibition of the uptake of D
      glucose and its non-metabolized analog by the BRIN-BD11 cells. These findings
      resemble those observed in acinar or ductal cells of the rat submaxillary gland
      and displayed a relative magnitude comparable to that found for the inhibition of
      D-glucose metabolism by cytochalasin B in purified pancreatic islet B cells.
      These findings reinforce the view that the primary site of action of cytochalasin
      B is located at the level of the plasma membrane.

PMID- 24944799
TI  - Effects of Tripterygium glycosides on interleukin-17 and CD4+CD25+CD127low
      regulatory T-cell expression in the peripheral blood of patients with ankylosing
      spondylitis.
AB  - The aim of this study was to investigate the possible mechanisms of action of
      Tripterygium glycosides (TG) in the treatment of ankylosing spondylitis (AS). In
      total, 20 patients with active AS received treatment with 20 mg TG tablet (TGT) 3
      times per day for 6 weeks. In addition, 20 healthy age- and gender-matched
      individuals were recruited as the control group. The efficacy measures included
      the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR)
      and C-reactive protein (CRP) levels. The serum interleukin (IL)-17 levels were
      measured using ELISA. The expression of CD4+CD25+CD127low regulatory T cells
      (Tregs) in the peripheral blood was evaluated by flow cytometry. A bivariate
      correlation analysis was used to determine the association of IL-17 levels with
      BASDAI, ESR, CRP and CD4+CD25+CD127low Tregs in AS patients. Prior to treatment,
      the BASDAI, ESR and CRP levels in AS patients were found to be elevated compared
      to those in healthy controls and were significantly reduced following TGT
      treatment (P<0.05, P<0.05 and P<0.05, respectively). Prior to treatment, the AS
      patients exhibited significantly higher IL-17 levels compared to those in healthy
      controls (P<0.05). Following TGT treatment, the IL-17 levels were significantly
      reduced in AS patients (P<0.01) but were not significantly different in the
      control subjects (P>0.05). In addition, prior to treatment, the ratio of
      CD4+CD25+CD127low Tregs in AS patients was significantly lower compared to that
      in healthy controls (P<0.05) and it was significantly increased following TGT
      treatment (P<0.05). The correlation analysis between the BASDAI, ESR or CRP
      levels and IL-17 revealed a positive linear correlation (P<0.001, P<0.001 and
      P<0.01, respectively), whereas CD4+CD25+CD127low Tregs were found to be
      negatively correlated with IL-17 (P<0.01). In conclusion, TGT is efficient for
      the treatment of AS patients and its mechanism of action may be correlated with
      the upregulation of CD4+CD25+CD127low Tregs and the downregulation of IL-17 in
      the peripheral blood.

PMID- 24944800
TI  - WRN Cys1367Arg polymorphism is not associated with skull base chordoma.
AB  - Skull base chordoma is a rare tumor with unknown risk factors. Werner syndrome,
      which is caused by a mutation in the WRN gene, is a disease of progeria,
      resembling the pathological process of aging. The present study aimed to provide
      data on the possible association between skull base chordoma and the single
      nucleotide polymorphism (SNP) rs1346044 of the WRN gene. Between July, 2010 and
      September, 2012, a total of 65 patients with pathologically confirmed skull base
      chordoma and 65 control subjects were enrolled in this case-control study. The
      clinical data of the skull base chordoma patients were documented and the
      rs1346044 site in all the enrolled subjects was analyzed by sequencing and
      statistically compared using SPSS software. The A allele was the dominant allele
      of the rs1346044. The comparisons of genotype distributions and allele
      frequencies did not reveal any significant difference between the groups
      [P=0.383, 95% confidence interval (CI): 0.346-1.505]. The clinicopathological
      factors were assessed and no statistically significant difference was observed.
      In conclusion, the present study suggested that there is no association between
      rs1346044 SNP and skull base chordomas, at least in the population analyzed.

PMID- 24944801
TI  - Abnormal promoter methylation of multiple tumor suppressor genes in human
      bronchial epithelial malignant cells.
AB  - Carcinoma of the lung is the leading cause of cancer-related mortality worldwide.
      In order to understand the pathogenesis of radiation-induced lung cancer, we
      adopted a model of transformed human bronchial epithelial cells (BEP2D) induced
      by alpha-particles. Methylation-specific polymerase chain reaction was performed
      to detect aberrant promoter methylation of multiple tumor suppressor genes,
      including p14ARF, p16INK4a, O6-methylguanine-DNA methyltransferase, glutathione S
      transferase P1 and death-associated protein kinase genes in the BEP2D cell line
      and its malignant transformant, the BERP35T1 cell line. Our results demonstrated
      the distinctive methylation pattern for these tumor suppressor genes in radiation
      induced malignant cells, as compared to their wild-type counterparts. Our study
      revealed epigenetic signatures for the characterization of radiation-mediated
      carcinogenesis and it may facilitate early diagnosis of patients at high risk for
      lung cancer.

PMID- 24944802
TI  - Maintenance of chaperone-mediated autophagy activity in cultured cells expressing
      mutant huntingtin.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      caused by mutant huntingtin (Htt) with an expanded polyglutamine tract. It has
      been reported that Htt regulates autophagy. However, it remains unclear whether
      mutant Htt affects chaperone-mediated autophagy (CMA). Our study aimed to
      investigate the effect of mutant Htt on CMA activity in cultured HEK293T cells. A
      HEK293T cell model of HD was produced by transient transfection of wild-type
      (20Q) or mutant (120Q) Htt plasmids. The effect of mutant Htt on two CMA
      components, lysosomal-associated membrane protein 2a (Lamp2a) and heat-shock
      cognate protein 70 (Hsc70), was determined by western blotting and
      immunofluorescent staining. We observed that mutant Htt did not significantly
      alter the expression of Lamp2a and Hsc70 when compared to normal Htt. These
      findings suggest that mutant Htt does not reduce CMA activity and that enhancing
      CMA activity to clear mutant Htt may be a novel strategy for the management of
      HD.

PMID- 24944803
TI  - Associations of genetic variants in ADAM33 and TGF-beta1 genes with childhood
      asthma risk.
AB  - The aim of the present study was to explore the associations of genetic variants
      in the ADAM33 and TGF-beta1 genes with the risk of childhood asthma. A total of
      299 asthmatic children and 311 healthy controls were recruited in the hospital
      based case-control study. The asthmatic subjects were further divided into mild
      and severe groups according to disease severity. Single-nucleotide polymorphisms
      (SNP) at ADAM33 V4, T2, S2 and T1, and TGF-beta1 C-509T and T869C were selected
      and detected with PCR-RFLP. The associations of the SNPs with asthma risk and
      severity were analyzed. The associations between the haplotypes of ADAM33 and TGF
      beta1 were also evaluated. Compared with the GG genotype, the GC and CC genotypes
      at V4 were associated with an increased asthma risk in children and the ORs were
      2.92 and 10.56, respectively. Compared with the CC genotype, the CT/TT genotype
      at C-509T was associated with an increased asthma risk and the OR was 2.26.
      Subsequent to stratification by asthma severity, compared with the V4 GG
      genotype, it was found that the CG and CC genotypes were associated with a mild
      asthma risk and the ORs were 3.00 and 5.99, respectively. The SNP at C-509T
      (CT/TT vs. CC) was associated with mild asthma (OR=2.34), whereas a marginally
      significant association was detected between the SNP (CT/TT vs. CC) and severe
      asthma risk (OR=2.19). The haplotype analysis revealed that, compared with the
      GGCA haplotype of ADAM33, significant associations of the haplotypes of CGCG,
      CGGA, GACA, GACG and GAGA with asthma risk were observed, and the ORs were 31.12,
      12.24, 4.73, 30.85 and 4.83, respectively. No significant association was
      detected between the TGF-beta1 haplotypes and asthma risk. The genetic variants
      at V4 and C-509T had the potential to modify the childhood asthma risk and the
      associations showed no notable difference with the disease severity. Thus, ADAM33
      haplotypes provided more useful information in the prediction of asthma risk.

PMID- 24944804
TI  - Stereoselective activity of 2-(4-amino-3-chloro-5- trifluomethyl-phenyl)-2-tert
      butylamino-ethanol hydrochloride to improve the pulmonary function in asthma.
AB  - Asthma is a chronic airway disease that is characterized by significantly
      exacerbated bronchospasms and marked inflammation of the airways. Although the
      etiology of asthma remains to be determined, genetic predisposition is one of the
      factors involved. beta2-agonists compounds may serve as options for the treatment
      of bronchial asthma. The aim of the present study was to investigate the effects
      of 2-(4-amino-3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-ethanol
      hydrochloride (SPFF) and its enantiomers with regard to improving asthmatic
      pulmonary function and selective binding to beta2-adrenergic receptor. The
      bronchoconstrictor action of histamine in guinea pigs was conducted and the
      results demonstrated that (-)SPFF and (+/-)SPFF could significantly inhibit the
      increase of bronchoconstriction induced by histamine, while (+)SPFF did not show
      an effect. Inflammatory mediator release from allergic lung tissues was
      determined and it was found that (+/-)SPFF showed the highest activity among all
      the tested compounds, while the efficacy of (-)SPFF was similar to that of
      (+)SPFF. SPFF and its enantiomers stimulated cyclic adenosine monophosphate
      (cAMP) production in the asthmatic lung tissues examined, showing that asthmatic
      lung tissues had a significant cAMP enhancement in response to (-)SPFF and (+/
      )SPFF compared with (+)SPFF. Cardiac contractility of the right atria was
      assessed in the guinea pigs to establish the receptor selectivity of the
      compounds. The results indicated that all the compounds had high affinities to
      the beta2 receptor. In conclusion, with regards to asthmatic pulmonary function
      improvement, (-)SPFF was more efficient as compared to (+)SPFF, while no
      significant difference was observed for the receptor selectivity of (-)SPFF and
      (+)SPFF.

PMID- 24944805
TI  - Pharmacokinetics of liver-targeted docetaxel liposomes modified with 6-O-acyl-D
      galactose esters in rabbits.
AB  - The purpose of the present study was to investigate the pharmacokinetics of
      docetaxel liposomes modified with 6-O-acyl-D-galactose esters (Gal-DOC-L) in
      rabbits. A simple, rapid and sensitive high-performance liquid chromatography
      (HPLC) method was developed for the determination of docetaxel. Gal-DOC-L was
      intravenously administered to rabbits with norethisterone as the internal
      standard and the blood samples were collected from ear marginal veins at 0.083,
      0.25, 0.5, l, 2, 4, 6, 8, 12, 16 and 24 h after treatment. The plasma
      concentration of docetaxel was determined by HPLC and the pharmacokinetic
      parameters were calculated. Docetaxel injection (DOC-I) was studied
      simultaneously. The results showed that the area under the curve(0-infinity),
      t1/2alpha and t1/2beta of Gal-DOC-L was significantly higher, while the total
      body clearance was lower than that of DOC-I. The results indicated that Gal-DOC-L
      was able to maintain a relatively high blood concentration in vivo and prolong
      the treatment time.

PMID- 24944807
TI  - Heat-shock protein 70-2 BB genotype is associated with reduced risks of the
      steroid-dependent and refractory phenotypes of ulcerative colitis.
AB  - Previous studies have demonstrated the protective role of inducible heat-shock
      protein (HSP) 70 in intestinal cells. The HSP70-2 gene has a PstI site due to an
      A-G transition at the 1,267 position and different genotypes are associated with
      various levels of mRNA expression. The present study aimed to clarify the effect
      of the HSP70-2 polymorphism on the risk of ulcerative colitis (UC), including its
      clinical phenotypes. A total of 121 patients with UC and 500 healthy control (HC)
      subjects participated in the study. To assess the polymorphisms at the 1,267
      position of the HSP70-2 gene, restriction fragment length polymorphism analysis
      was performed. The subjects in the study were classified by disease behavior,
      severity and extent of disease. Although no significant difference of the HSP70-2
      genotype distribution was identified between the HC and UC groups, the BB
      genotype exhibited a lower risk of the steroid-dependent phenotype [odds ratio
      (OR), 0.12; 95% confidence interval (CI), 0.02-0.95; P=0.02]. The same genotype
      was also associated with a lower risk of the refractory phenotype (OR, 0.16; 95%
      CI, 0.04-0.73; P=0.01). There was no direct correlation between the polymorphism
      of the HSP70-2 gene and UC susceptibility. However, there was an association
      between a reduced risk of the steroid-dependent and refractory phenotypes of UC
      and the BB genotype.

PMID- 24944806
TI  - CCND1 G870A polymorphism contributes to the risk of esophageal cancer: An updated
      systematic review and cumulative meta-analysis.
AB  - The common functional cyclin D1 (CCND1) G870A polymorphism may influence the risk
      of esophageal cancer. However, the conclusions of previous studies have been
      inconsistent for the association between the CCND1 G870A polymorphism and
      esophageal cancer risk. A meta-analysis of 11 published case-control studies was
      performed, including 2,111 patients with esophageal cancer and 3,232 controls, to
      investigate the association between the CCND1 G870A polymorphism and esophageal
      cancer risk. The odds ratio (OR) with a 95% confidence interval (CI) was applied
      to assess the association between the CCND1 G870A polymorphism and esophageal
      cancer risk. A significant association between the CCND1 G870A polymorphism and
      esophageal cancer risk was observed for the allele contrast (A vs. G: OR, 1.23;
      95% CI, 1.02-1.48; P=0.029), codominant (AA vs. GG: OR, 1.58; 95% CI; 1.06-2.35;
      P=0.024) and recessive models (AA vs. GG + GA: OR, 1.33, 95% CI, 1.03-1.73;
      P=0.030). However, in the stratified analysis by ethnicity, study design and
      pathology, there was no significant association detected in these genetic models.
      In conclusion, results of the meta-analysis suggested that the CCND1 G870A
      polymorphism is a potential risk factor in the development of esophageal cancer.

PMID- 24944808
TI  - Calcium butyrate: Anti-inflammatory effect on experimental colitis in rats and
      antitumor properties.
AB  - Butyric acid is a physiological component of the colonic environment that
      possesses anti-inflammatory and antitumor properties, among others. However,
      little is known regarding its effects following direct application on the colonic
      surface. This study was conducted to investigate the topical anti-inflammatory
      effect of calcium butyrate in chemically-induced colitis in rats and to evaluate
      its antitumor properties in vivo and in vitro. The anti-inflammatory activity of
      calcium butyrate was evaluated in dinitrobenzene sulfonic acid-induced colitis in
      rats, following intracolonic instillation for 6 consecutive days and its in vivo
      antitumor activity was evaluated in F344 rats with the azoxymethane (AOM)-induced
      aberrant crypt foci (AFC) test, following intracolonic instillation for 4 weeks.
      The in vitro antiproliferative activity was assessed by incubation for 48 h with
      the HT29, SW620 and HCT116 intestinal tumour cell lines to evaluate the rate of
      3H-thymidine uptake. In dinitrobenzene-induced colitis, the intracolonic
      instillation of calcium butyrate completely prevented body weight reduction in
      the animals and counteracted the local noxious effects of the irritant by
      reducing colon edema (-22.7%, P=0.048) and the area of mucosal damage (-48%,
      P=0.045). In the AOM-induced AFC test, the intracolonic instillation of calcium
      butyrate significantly reduced the number of AFC in the entire colon (-22.7%,
      P<0.05). Calcium butyrate, following incubation with the HT29, SW620 and HCT116
      tumour cell lines, induced a significant antiproliferative, dose-dependent effect
      (P=0.046 to P=0.002) in all three strains, as measured by the reduction in 3H
      thymidine uptake. Calcium butyrate directly applied to the mucosa of the rat
      colon was able to ameliorate colonic inflammation, suggesting a possible
      beneficial role in the treatment of inflammatory colon diseases. Moreover,
      calcium butyrate exhibited notable antitumor effects in vivo and in vitro;
      however, their clinical relevance requires confirmation by additional clinical
      investigations.

PMID- 24944809
TI  - The differentiation effect of low-dose cytosine arabinoside is disturbed in PU.1
      knockdown K562 cells.
AB  - We recently demonstrated by using PU.1-knockdown K562 (K562 PU.1KD) cells stably
      expressing PU.1 short inhibitory RNAs and PU.1-overexpressing K562 (K562 PU.1OE)
      cells, that therapeutic concentrations of 5-aza-2'-deoxycytidine (5-azadC) induce
      erythroid differentiation of these cells and that the PU.1 expression level is
      closely associated with the differentiating and apoptotic effects of 5-azadC on
      K562 cells. In this study, we investigated whether the effects of low-dose
      cytosine arabinoside (Ara-C), which is another erythroid differentiation inducer
      in K562 cells, is associated with the expression level of PU.1 in these cells. As
      a result, we demonstrated that the effect of Ara-C on cell viability and
      differentiation, as determined by the WST-8 assay and beta-globin mRNA expression
      analysis, respectively, was suppressed in K562 PU.1KD cells compared to their
      controls. Collectively, these findings suggest that sufficient expression of PU.1
      is indispensable for the erythroid differentiation of K562 cells.

PMID- 24944810
TI  - Analgesic effects of naringenin in rats with spinal nerve ligation-induced
      neuropathic pain.
AB  - Naringenin, a flavonoid abundant in citrus fruits, such as grapefruits, has been
      reported to possess anti-inflammatory properties. The present study aimed to
      investigate the analgesic potential of naringenin in L5 spinal nerve ligation
      (SNL)-induced peripheral neuropathic pain and the underlying mechanisms
      associated with neuroinflammation. Different doses of naringenin or saline were
      administered intrathecally once daily for 11 consecutive days, from 3 days prior
      to surgery to 7 days after surgery. Pain development was assessed 1 day prior to
      and 7-14 days after surgery in terms of mechanical withdrawal threshold and
      thermal withdrawal latency. Astrocytic and microglial activation and production
      of inflammatory mediators were determined on day 14 after surgery. The results
      demonstrated that naringenin dose-dependently attenuated the mechanical allodynia
      and thermal hyperalgesia induced by SNL. Furthermore, naringenin significantly
      inhibited SNL-induced activation of glial cells (astrocytes and microglia).
      Morover, the upregulated expression of inflammatory mediators in neuropathic pain
      was significantly inhibited by naringenin. Our findings suggested that repeated
      administration of naringenin may alleviate neuropathic pain, possibly through
      inhibiting neuroinflammation.

PMID- 24944812
TI  - Antiplasmodial properties of kaempferol-3-O-rhamnoside isolated from the leaves
      of Schima wallichii against chloroquine-resistant Plasmodium falciparum.
AB  - Previous intervention studies have shown that the most effective agents used in
      the treatment of malaria were isolated from natural sources. Plants consumed by
      non-human primates serve as potential drug sources for human disease management
      due to the similarities in anatomy, physiology and disease characteristics. The
      present study investigated the antiplasmodial properties of the primate-consumed
      plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has
      already been reported to have several biological activities. The ethanol extract
      of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate
      and water. The antiplasmodial activity was tested in vitro against chloroquine
      resistant Plasmodium falciparum (P. falciparum) at 100 MUg/ml for 72 h. The major
      compound of the most active ethyl acetate fraction was subsequently isolated
      using column chromatography and identified by nuclear magnetic resonance. The
      characterized compound was also tested against chloroquine-resistant P.
      falciparum in culture to evaluate its antiplasmodial activity. The ethanol
      extract of S. wallichii at 100 MUg/ml exhibited a significant parasite shrinkage
      after 24 h of treatment. The ethyl acetate fraction at 100 MUg/ml was the most
      active fraction against chloroquine-resistant P. falciparum. Based on the
      structural characterization, the major compound isolated from the ethyl acetate
      fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial
      activity against chloroquine-resistant P. falciparum with an IC50 of 106 MUM
      after 24 h of treatment. The present study has provided a basis for the further
      investigation of kaempferol-3-O-rhamnoside as an active compound for potential
      antimalarial therapeutics.

PMID- 24944811
TI  - Changes in human sirtuin 6 gene promoter methylation during aging.
AB  - Aging is a natural process during which changes at the cellular level increase
      death risk by developing susceptibility to a variety of diseases. Sirtuins have
      been shown to regulate lifespan in various organisms by deacetylating a number of
      important transcription factors. Of the 7 identified mammalian sirtuins (SIRT1
      7), SIRT6 depletion is associated with severe symptoms of premature aging. In
      this study, we investigated the association between human longevity and SIRT6
      promoter methylation. Genomic DNA from blood samples of 55 individuals (34
      females and 21 males) was examined to detect methylation levels by quantitative
      polymerase chain reaction analysis following bisulfite treatment. While the
      results indicated 43.21% methylation in the 9-19 age group, this ratio was found
      to be increased up to 65.63% in the 20-79 age group and decreased to 52.15% in
      the 80-95 age group. Our results demonstrated that the SIRT6 gene is more active
      between 9-19 and 80-95 years compared to 20-79 years.

PMID- 24944813
TI  - Effect of pertussis toxin on calcium influx in three contraction models.
AB  - Pertussis toxin (PTX) blocks G protein activation and inhibits signal
      transmission from the activated receptor to effectors that are specific for the G
      protein-coupled receptor. The aim of the present study was to evaluate the effect
      of PTX on vascular smooth muscle cells that were stimulated pharmacologically
      with phenylephrine (alpha-adrenoceptor agonist), mastoparan-7 (direct G-protein
      activator) and Bay K8644 (direct calcium channel activator). The changes in
      perfusion pressure that were proportional to the degree of phenylephrine-induced
      constriction of rat tail arteries were assessed. Concentration-response curves
      (CRCs) that were obtained for phenylephrine, mastoparan-7 and Bay K8644 presented
      a sigmoidal association. A significantly reduced calcium influx to the cytoplasm
      in the presence of mastoparan-7 resulted in a significant rightward shift of the
      CRCs with a significant reduction in maximal responses. The presence of PTX did
      not change mastoparan-7 and Bay K8644-induced contraction, whereas the
      significant inhibition of phenylephrine-induced contraction was found. The
      results of the experiments indicated that PTX significantly inhibited
      phenylephrine-induced contraction of vascular smooth muscle cells by inhibition
      of calcium influx from the intra- and extracellular calcium space. PTX did not
      change the smooth muscle contraction that was induced by mastoparan-7 and Bay
      K8644. The predominant effect of mastoparan-7 may be associated with other
      binding sites as compared to the G-protein or PTX may bind to other sites than
      mastoparan-7.

PMID- 24944815
TI  - Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin
      2 gene.
AB  - Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by
      mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 (AQP2)
      genes. The current study presented the case of CNDI in a 1-month-old male with a
      novel mutation in the AQP2 gene. The patient was referred due to the occurrence
      of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test
      was compatible with CNDI as there was no significant response to desmopressin.
      Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene:
      C to T transition, which resulted in a missense mutation of 108Thr (ACG) to Met
      (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine
      in position 43 at codon CAG as the first affected amino acid, with the new
      reading frame endign in a termination codon at position 62. The molecular genetic
      analysis of the parents showed that the missense mutation was inherited
      maternally and the deletion mutation was inherited paternally. The parents showed
      no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The
      108Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore,
      the molecular identification of the AQP2 gene has clinical significance, as early
      recognition of CNDI in infants that show only non-specific symptoms, can be
      facilitated. Thus, repeated episodes of dehydration, which may cause physical and
      mental retardation can be avoided.

PMID- 24944816
TI  - SLC41A1, a Na+/Mg2+ exchanger, is downregulated during exercise.
AB  - Serum magnesium (Mg) levels are closely controlled through a variety of Mg
      transporters and ionic channels during physiological conditions. These levels
      have been shown to increase during exercise. However, the effect of Mg
      transporter expression during exercise remains to be determined. The purpose of
      this study was to examine the gene expression of SLC41A1, a Na+/Mg2+ exchanger,
      during exercise. In the present study, male C57BL/6JNarl mice (n=16, 8 weeks old)
      were subjected to 3 h forced exercise on a treadmill. The mice in the control and
      Mg groups were injected with saline and Mg (MgSO4, 90 mg/kg, intraperitoneal),
      respectively. Blood samples were obtained at three time points: prior to,
      following and 24 h after exercise. The gene expression levels of SLC41A1 were
      significantly downregulated to 23.6+/-4.6 and 12.6+/-10.2% following exercise in
      the control and Mg groups, respectively. The expression levels returned to the
      basal levels 24 h after exercise in the two groups and there was no significant
      difference found between the two groups. The downregulated role of SLC41A1
      expression and its interaction with the Mg status in exercise requires further
      investigation.

PMID- 24944814
TI  - Association between p16(CDKN2A) C540G polymorphism and tumor behavior in
      prolactinoma: A single-center study.
AB  - Pituitary tumors usually originate as benign sporadic adenomas and develop into
      invasive and aggressive tumors such as prolactinomas, which are common
      functioning pituitary adenomas. The aim of the present study was to examine the
      association between the tumor behavior in prolactinomas and the p16(CDKN2A) gene
      polymorphism occurring at the 3'-untranslated region of exon 3 (C540G). A total
      of 104 patients with prolactinoma were included and assigned to two groups based
      on invasive vs. non-invasive tumor behavior. Ki67 indices were recorded according
      to histopathology results. Genotypic analysis of the p16(CDKN2A) C540G
      polymorphism was carried out using a modified polymerase chain reaction
      restriction fragment length polymorphism assay. The corresponding frequencies for
      CC, CG and GG genotypes in non-invasive vs. invasive tumors were 61.5, 30.8, 7.7
      and 64.1, 28.2, 7.7%, respectively (not significant). The observed CG genotype
      frequency was higher compared with previous studies. In addition, the patients
      with giant adenomas or a high Ki67 index had a higher frequency of the CG
      genotype as compared with the other subgroups, although the differences were not
      significant (46.2 and 42.9%, respectively). In conclusion, a higher frequency of
      the C540G CG genotype of the CDKN2A gene was found among patients with
      prolactinoma in comparison with previous studies. These frequencies were also
      higher in the subgroups with elevated Ki67 or giant adenomas. Further studies are
      required to improve the definition of the role of the CG genotype in the
      development and progression of tumors in prolactinomas.

PMID- 24944817
TI  - Effect of RANTES gene promoter genotypes in patients with ulcerative colitis.
AB  - A complex interaction of genetic and environmental factors is closely associated
      with the development of inflammatory bowel disease. Previous studies reported
      that the expression of the regulated upon activation, normal T-cell expressed and
      secreted (RANTES) gene is enhanced in the colonic mucosa of ulcerative colitis
      (UC). Quantitative differences in RANTES gene expression among numerous promoter
      genotypes have also been reported. The aim of the present study was to clarify
      the effect of RANTES promoter polymorphism on the risk of UC, including its
      clinical phenotypes. A total of 150 UC patients and 372 healthy control (HC)
      subjects participated in the study. The UC patients were classified by disease
      behavior, severity and extent of disease. Restriction fragment length
      polymorphism analysis was performed for polymorphisms at -28 C/G in the RANTES
      gene promoter region. Although no significant difference of the RANTES promoter
      genotype distribution was observed between the HC and UC groups, the G/G genotype
      was significantly higher among female (OR=3.95, 95% CI=1.22-12.82, P=0.03), non
      steroid dependent (OR=3.37, 95% CI=1.16-9.85, P=0.03) and non-refractory
      (OR=3.76, 95% CI=1.29-10.98, P=0.02) UC patients. The G carrier was also found to
      be associated with an increased risk of rectal colitis (OR=2.21, 95% CI=1.12
      4.39, P=0.03). The data indicate that the polymorphism of the RANTES promoter is
      not directly associated with the susceptibility to UC, but the -28 G allele is
      associated with female UC patients and mild clinical phenotypes of UC, including
      non-steroid dependency, non-refractory and rectal colitis.

PMID- 24944818
TI  - Calibration of (192)Ir high dose rate brachytherapy source using different
      calibration procedures.
AB  - AIM: To calibrate Ir-192 high dose rate (HDR) brachytherapy source using
      different calibration methods and to determine the accuracy and suitability of
      each method for routine calibrations. BACKGROUND: The source calibration is an
      essential part of the quality assurance programme for dosimetry of brachytherapy
      sources. The clinical use of brachytherapy source requires an independent
      measurement of the air kerma strength according to the recommendations of medical
      physics societies. MATERIALS AND METHODS: The Ir-192 HDR brachytherapy source
      from Gammamed plus machine (Varian Medical Systems, Palo Alto, CA) was calibrated
      using three different procedures, one using the well-type ionization chamber,
      second by the in-air calibration method and third using solid water phantoms. The
      reference air kerma rate (RAKR) of the source was determined using Deutsche
      Gesellschaft fur Medizinische Physik (DGMP) recommendations. RESULTS: The RAKR
      determined using different calibration methods are in good agreement with the
      manufacturer stated value. The mean percentage variations of 0.21, -0.94, -0.62
      and 0.58 in RAKR values with respect to the manufacturer quoted values were
      observed with the well-type chamber, in-air calibration, cylindrical phantom and
      slab phantom measurements, respectively. CONCLUSION: Measurements with a well
      type chamber are relatively simple to perform. For in-air measurements, the
      indigenously designed calibration jig provides an accurate positioning of the
      source and chamber with minimum scatter contribution. The slab phantom system has
      an advantage that no additional phantom and chamber are required other than those
      used for external beam therapy dosimetry. All the methods of calibration
      discussed in this study are effective to be used for routine calibration
      purposes.

PMID- 24944820
TI  - Silver binding nucleolar organizer regions dots in oral leukoplakia with
      epithelial dysplasia and oral squamous cell carcinoma: an in vivo study.
AB  - Silver binding nucleolar organizer regions (AgNOR) in normal oral mucosa (NOM),
      oral leukoplakia with epithelial dysplasia (ED), and oral squamous cell carcinoma
      (OSCC) were studied. The mean AgNOR count per nucleus increased from NOM to ED to
      OSCC. Tissue showing ED in oral leukoplakia and OSCC cases showed higher counts,
      wider scatter, and smaller size of AgNOR dots in the nuclei. The study seems to
      suggest that time method has some potential in distinguishing between NOM and
      oral leukoplakia with ED and OSCC. Studies of larger numbers are needed to arrive
      at more substantial conclusions. 

PMID- 24944819
TI  - The impact of PET/CT scanning on the size of target volumes, radiation exposure
      of organs at risk, TCP and NTCP, in the radiotherapy planning of non-small cell
      lung cancer.
AB  - AIM: To compare radiotherapy plans made according to CT and PET/CT and to
      investigate the impact of changes in target volumes on tumour control probability
      (TCP), normal tissue complication probability (NTCP) and the impact of PET/CT on
      the staging and treatment strategy. BACKGROUND: Contemporary studies have proven
      that PET/CT attains higher sensitivity and specificity in the diagnosis of lung
      cancer and also leads to higher accuracy than CT alone in the process of target
      volume delineation in NSCLC. MATERIALS AND METHODS: Between October 2009 and
      March 2012, 31 patients with locally advanced NSCLC, who had been referred to
      radical radiotherapy were involved in our study. They all underwent planning
      PET/CT examination. Then we carried out two separate delineations of target
      volumes and two radiotherapy plans and we compared the following parameters of
      those plans: staging, treatment purpose, the size of GTV and PTV and the exposure
      of organs at risk (OAR). TCP and NTCP were also compared. RESULTS: PET/CT
      information led to a significant decrease in the sizes of target volumes, which
      had the impact on the radiation exposure of OARs. The reduction of target volume
      sizes was not reflected in the significant increase of the TCP value. We found
      that there is a very strong direct linear relationship between all evaluated
      dosimetric parameters and NTCP values of all evaluated OARs. CONCLUSIONS: Our
      study found that the use of planning PET/CT in the radiotherapy planning of NSCLC
      has a crucial impact on the precise determination of target volumes, more precise
      staging of the disease and thus also on possible changes of treatment strategy.

PMID- 24944821
TI  - Prevalence of coronal pulp stones and its relation with systemic disorders in
      northern Indian central punjabi population.
AB  - Aim. To estimate the prevalence of coronal pulp stones in the molar teeth of
      dental outpatients of Sunam, Sangrur district, Punjab, India, to report any
      association between occurrence of pulp stones with age, gender, dental arch,
      side, and dental status and to find out correlation between pulp stones with
      dental and systemic diseases. Materials and Methods. 500 routine dental
      outpatients within age group of 18-67 years were involved in the study. Molar
      bitewing of left and right side of each patient was taken with XCP bitewing
      instrument and size 2 film. The presence or absence of pulp stones was recorded.
      Chi-square analysis was used to record the prevalence of pulp stones and to
      compare it with demographic and systemic factors. Results. Overall prevalence of
      pulp stones was 41.8%. Pulp stones were significantly higher in maxilla (11.59%)
      than mandible (6.54%), left side than right side, and first molar than other
      molars. Higher numbers of pulp stones were recorded in patients with
      cardiovascular disease (38.89%) than with cholelithiasis and renal lithiasis.
      Conclusion. Pulp stones were higher in maxillary arch than mandibular arch and in
      females than males. Cardiovascular patients had higher number of pulp stones than
      other groups. 

PMID- 24944822
TI  - An insight into internal resorption.
AB  - Internal resorption, a rare phenomenon, has been a quandary from the standpoints
      of both its diagnosis and treatment. It is usually asymptomatic and discovered by
      chance on routine radiographic examinations or by a classic clinical sign, "pink
      spot" in the crown. This paper emphasizes the etiology and pathophysiologic
      mechanisms involved in internal root resorption. Prognosis is good for smaller
      lesions; however, for those with extensive resorption associated with perforation
      the tooth structure is greatly weakened and the prognosis remains poor. 

PMID- 24944823
TI  - A Survey of Standard Protocols for Endodontic Treatment in North of KSA.
AB  - The objective of this study was to collect information regarding methods,
      materials, and attitudes employed during the endodontic treatment by dentists in
      north of Saudi Arabia. A questionnaire was designed and distributed among 300
      dentists in north of Saudi Arabia to collect the data about the standard
      protocols of endodontic treatment. The collected data was analyzed by using the
      SPSS 10 computer software. Out of a total of 300 surveyed dentists, the 66%
      response rate showed that this study was true representation of the endodontic
      treatment performed by the dentists in north of Saudi Arabia. 152 (76%) were
      general dentists and 48 (24%) were endodontists. 18 (9%) were using rubber dam as
      the method of isolation during endodontic treatment. 173 (86.5%) were using only
      measurement radiographs for working length determination and 27 (13.5%) were
      using both electronic apex locator and measurement radiographs. 95 (47.5%) of the
      respondents were using standardized technique and 25 (12.5%) were using step-down
      as a root canal preparation technique. 127 (63.5%) of the respondents were using
      lateral condensation technique, with gutta percha points for root canal
      obturation. 

PMID- 24944824
TI  - The risk of endoscopic mucosal resection in the setting of clopidogrel use.
AB  - Objective. Guidelines on antiplatelet medication use during endoscopy are based
      on limited evidence. We investigate the risk of bleeding and ischemic events in
      patients undergoing endoscopic mucosal resection (EMR) of esophageal lesions in
      the setting of scheduled cessation and prompt resumption of clopidogrel. Design.
      Single centre retrospective review. Patients. Patients undergoing EMR of
      esophageal lesions. Interventions. Use of clopidogrel before EMR and resumption
      after EMR. Patients cease antiplatelets and anticoagulants 7 days before EMR and
      resume clopidogrel 2 days after EMR in average risk patients. Main Outcomes.
      Gastrointestinal bleeding (GIB) and ischemic events (IE) within 30 days of EMR.
      Results. 798 patients underwent 1716 EMR. 776 EMR were performed on patients on
      at least 1 antiplatelet/anticoagulant (APAC). 17 EMR were performed following
      clopidogrel cessation. There were 14 GIB and 2 IE. GIB risk in the setting of
      recent clopidogrel alone (0%) was comparable to those not on APAC (1.1%) (P =
      1.0). IE risk on clopidogrel (6.3%) was higher than those not on APAC (0.1%) (P =
      0.03). Limitations. Retrospective study. Conclusions. Temporary cessation of
      clopidogrel before EMR and prompt resumption is not associated with an increased
      risk of gastrointestinal bleeding but may be associated with increased ischemic
      events. 

PMID- 24944826
TI  - Antihyperglycaemic effect of tetracarpidium conophorum nuts in alloxan induced
      diabetic female albino rats.
AB  - The antihyperglycaemic activity of Tetracarpidium conophorum nut (walnut) was
      investigated in albino rats. A total of 20 albino rats were used for the study.
      The rats were divided into five groups (A-E) of four rats each. Diabetes were
      induced in the rats except four which served as the positive control group A.
      Groups B (negative control), C, D, and E contain diabetic rats each with blood
      sugar level >=17.00 mmol/L. Groups A and B were fed on 85.2 g of top feed grower
      over the test period. Test groups C, D, and E were fed on 21.3 g, 42.6 g, and
      85.2 g of walnuts, respectively, and their fasting blood sugar (FBS) levels were
      checked on daily basis. Fasting blood glucose levels of the test groups were
      significantly lower than negative control P < 0.05, for 3rd, 7th, and 10th days
      of the test. There were also significant increase in the body weight and
      hemoglobin concentration and a decreased urine output of the test group compared
      with the controls. These results indicate that Tetracarpidium conophorum nut
      (walnut) has an antihyperglycemic effect in diabetic rats. 

PMID- 24944825
TI  - Effect of treatment with ginger on the severity of premenstrual syndrome
      symptoms.
AB  - Premenstrual syndrome (PMS) is a common disorder. Although the etiology of PMS is
      not clear, to relieve from this syndrome different methods are recommended. One
      of them is use of medicinal herbs. This study was carried out to evaluate effects
      of ginger on severity of symptoms of PMS. This study was a clinical trial, double
      blinded work, and participants were randomly allocated to intervention (n = 35)
      and control (n = 35) groups. To determine persons suffering from PMS,
      participants completed daily record scale questionnaire for two consecutive
      cycles. After identification, each participant received two ginger capsules daily
      from seven days before menstruation to three days after menstruation for three
      cycles and they recorded severity of the symptoms by daily record scale
      questionnaire. Data before intervention were compared with date 1, 2, and 3
      months after intervention. Before intervention, there were no significant
      differences between the mean scores of PMS symptoms in the two groups, but after
      1, 2, and 3 months of treatment, there was a significant difference between the
      two groups (P < 0.0001). Based on the results of this study, maybe ginger is
      effective in the reduction of severity of mood and physical and behavioral
      symptoms of PMS and we suggest ginger as treatment for PMS. 

PMID- 24944827
TI  - Synthesis, Spectral Analysis, In Vitro Microbiological Evaluation, and Molecular
      Docking Studies of Some Novel 1-(1-Aryl-1H-tetrazol-5-yl)-2-(piperidin-1
      yl)ethanone Derivatives.
AB  - A new series of novel heterocyclic compounds containing both tetrazoles and
      piperidine nuclei together, namely, 1-(1-aryl-1H-tetrazol-5-yl)-2-(piperidin-1
      yl)ethanone (22-28), were synthesized by the treatment of the respective 2-chloro
      1-(1-aryl-1H-tetrazol-5-yl)ethanone (15-21) with piperidine in acetonitrile for 6
      h. A series of novel tetrazole substituted piperidine derivatives were
      synthesized and evaluated for their antimicrobial activity using serial dilution
      method. The structures of the synthesized compounds were characterized by IR,
      (1)H NMR, (13)C NMR, mass spectral data, and elemental analysis. Evaluation of
      antimicrobial activity shows that several compounds exhibit good activity when
      compared with the reference drug candidates and thus could be promising new lead
      molecules. 

PMID- 24944828
TI  - Crystal structure and stereochemistry study of 2-substituted benzoxazole
      derivatives.
AB  - The structure of 2-[(4-chlorophenylazo) cyanomethyl] benzoxazole, C15H9ClN4O (I),
      has triclinic ([Formula: see text]) symmetry. The structure displays N-H ? N
      hydrogen bonding. The structure of 2-[(arylidene) cyanomethyl] benzoxazoles,
      C17H10N2O3 (II), has triclinic ([Formula: see text]) symmetry. The structure
      displays C-H ? N, C-H ? C hydrogen bonding. In (I), the chlorophenyl and
      benzoxazole groups adopt a trans configuration with respect to the central
      cyanomethyle hydrazone moiety. Compound (II) crystallized with two molecules in
      the asymmetric unit shows cisoid conformation between cyano group and benzoxazole
      nitrogen, contrary to (I). In (II) the benzodioxole has an envelope conformation
      (the C17 atom is the flap atom). The molecular geometry obtained using molecular
      mechanics (MM) calculations has been discussed along with the results of single
      crystal analysis. 

PMID- 24944830
TI  - The human epidermal growth factor receptor 2 screening tests for breast cancer
      suggested by the new updated recommendation of the american society of clinical
      oncology/college of american pathologists will involve a rise of the in-situ
      hybridization tests for the European laboratories of pathology.
AB  - Aims. The differences between the 2007 and the 2013 ASCO/CAP HER2 guidelines have
      been compared. We also discussed the potential consequences in our pathological
      practice. Material and Methodology. 189 HER2 fluorescence in situ hybridisation
      (FISH) tests were performed from 1016 preliminary HER2 immunohistochemical tests
      (IHC). All cases were reviewed and reclassed following the 2007 and 2013 ASCO/CAP
      recommendations. Results. The 2013 version decreased false-negative IHC (3/118
      versus 1/54, P = ns) and created more 2+ IHC (40/186 versus 89/186, P = 0.001) or
      more 3+ IHC (9/186 versus 39/186, P = 0.001). One false-positive IHC was
      described for the 2013 version (0/9 versus 1/39, P = ns). Equivocal FISH was
      reduced (8/186 versus 2/186, P = ns). An estimation based on our data for 1000
      patients showed a rise of our FISH tests for the control of 2+ IHC (180 tests for
      the 2007 version versus 274 tests for the 2013 version or FISH work overflow is
      +52%) and for the control of 2+/3+ IHC (300 for the 2007 version versus 475 for
      the 2013 version or FISH work overflow is +58%). Conclusions. The new 2013
      ASCO/CAP guidelines have detected more HER2 positive cases but have increased the
      number of FISH tests. 

PMID- 24944831
TI  - Comparative Study between Measurement Data and Treatment Planning System (TPS) in
      Small Fields for High Energy Photon Beams.
AB  - To achieve tumor control for radiotherapy, a dose distribution is planned which
      has a good chance of sterilizing all cancer cells without causing unacceptable
      normal tissue complications. The aim of the present study was to achieve an
      accurate calculation of dose for small field dimensions and perform this by
      evaluating the accuracy of planning system calculation. This will be compared
      with real measurement of dose for the same small field dimensions using different
      detectors. Practical work was performed in two steps: (i) determination of the
      physical factors required for dose estimation measured by three ionization
      chambers and calculated by treatment planning system (TPS) based on the latest
      technical report series (IAEATRS-398) and (ii) comparison of the calculated and
      measured data. Our data analysis for small field is irradiated by photon energy
      matched with the data obtained from the ionization chambers and the treatment
      planning system. Radiographic films were used as an additional detector for the
      obtained data and showed matching with TPS calculation. It can be concluded that
      studied small field dimensions were averaged 6% and 4% for 6 MV and 15 MV,
      respectively. Radiographic film measurements showed a variation in results within
      +/-2% than TPS calculation. 

PMID- 24944829
TI  - Review on Effectiveness of Primary Prophylaxis in aPLs with and without Risk
      Factors for Thrombosis: Efficacy and Safety.
AB  - Context. Antiphospholipid antibodies syndrome is an autoimmune disorder that is
      characterized by the association between presence of antiphospholipid antibodies
      and risk of thrombosis and/or pregnancy morbidity. Objectives. To systematically
      review the evidence for primary prophylaxis in patients with antiphospholipids
      antibodies syndrome or APS with or without other traditional risk factors of
      thrombosis when they did not have any thrombotic event yet. Methods. PubMed, the
      Cochrane Library, and Allied Health Literature were searched for studies that
      examined the efficacy and safety of primary prophylaxis in aPL patients from 1990
      to February 2013. We examined literature looking at patients with aPLs with other
      risk factors for thrombosis and aPLs with no additional risk factors for
      thrombosis. Conclusion. We concluded that, in patients with aPLs, primary
      prophylaxes with HCQ and aspirin have been observed to reduce the frequency of
      thrombotic events in the case of asymptomatic aPL-positive patients with SLE. We
      also in this study concluded that LDA was effective in patients with autoimmune
      diseases. Independent cardiovascular risk factors include autoimmune defects such
      as SLE, rheumatoid arthritis, and atherosclerosis, where overall venous
      thrombosis will be induced by systemic inflammation. This review concludes that
      HCQ is an effective primary approach when compared to aspirin. 

PMID- 24944832
TI  - A physiological neural controller of a muscle fiber oculomotor plant in
      horizontal monkey saccades.
AB  - A neural network model of biophysical neurons in the midbrain is presented to
      drive a muscle fiber oculomotor plant during horizontal monkey saccades. Neural
      circuitry, including omnipause neuron, premotor excitatory and inhibitory burst
      neurons, long lead burst neuron, tonic neuron, interneuron, abducens nucleus, and
      oculomotor nucleus, is developed to examine saccade dynamics. The time-optimal
      control strategy by realization of agonist and antagonist controller models is
      investigated. In consequence, each agonist muscle fiber is stimulated by an
      agonist neuron, while an antagonist muscle fiber is unstimulated by a pause and
      step from the antagonist neuron. It is concluded that the neural network is
      constrained by a minimum duration of the agonist pulse and that the most dominant
      factor in determining the saccade magnitude is the number of active neurons for
      the small saccades. For the large saccades, however, the duration of agonist
      burst firing significantly affects the control of saccades. The proposed saccadic
      circuitry establishes a complete model of saccade generation since it not only
      includes the neural circuits at both the premotor and motor stages of the saccade
      generator, but also uses a time-optimal controller to yield the desired saccade
      magnitude. 

PMID- 24944833
TI  - Evaluation of reliability of ultrasonographic parameters in differentiating
      benign and metastatic cervical group of lymph nodes.
AB  - The aim of the current study is to determine the efficacy of ultrasound in
      differentiating between benign and metastatic group of cervical lymph nodes. The
      study included forty-five subjects who were divided into three groups with 15 in
      each, by stratified random sampling method. Group 1 comprised fifteen patients
      without signs and symptoms of any infection and neoplasms in head and neck region
      (control group). Group 2 included fifteen patients with signs and symptoms of
      malignancy in head and neck region. Group 3 consisted of fifteen patients with
      signs and symptoms of odontogenic infections. "MY LAB-40" ultrasound machine with
      linear array transducer of 7.5 MHZ frequency was used for detecting cervical
      lymph nodes following Hajek's classification. The patients further underwent
      ultrasound guided FNAC under standard aseptic protocol and samples were subjected
      to cytopathological evaluation. Chi square analysis and one way ANOVA test were
      applied to obtain the results. We concluded that ultrasound and USG FNAC can be
      used accurately to assess the status of lymph nodes. The ultrasonographic
      features of lymph nodes with round shape, absence of hilar echo, sharp nodal
      borders, hyperechoic internal echogenicity, and presence of intranodal necrosis
      were highly suggestive of metastatic cervical lymph nodes. 

PMID- 24944834
TI  - Comparative Study of Snodgrass and Mathieu's Procedure for Primary Hypospadias
      Repair.
AB  - Objective. Present study was undertaken to compare the results of two single
      stage hypospadias repairs, namely, Tubularized Incised Plate (TIP) repair and
      Mathieu's repair. Methods. The study included 100 patients of distal penile
      hypospadias, from January, 2008 to January, 2013. After a detailed history, local
      examination was performed with reference to the site of meatus, shape of glans,
      and presence of chordee. TIP repair was performed in 52 patients and Mathieu's
      repair in 48 patients. On follow-up, the patients were examined for the position
      of meatus, shape of meatus, urinary stream, urethrocutaneous fistula, and
      stricture formation. Results. The mean age of presentation was 6.2 +/- 3.2 years
      (range 1.5-15years). The mean operative time was 63.7 +/- 14.3 (45-90) minutes
      and 95.0 +/- 19.1 (70-125) minutes in TIP and Mathieu's repair,
      respectively.Complications after surgery were urethero cutaneous fistula in
      3(5.76%) and 7 (14.5%), meatal stenosis in 3(5.33%) and 4(8.33%), wound infection
      in 19.2% and 8.3% cases in TIP repair and Mathieu repair, respectively. The shape
      of meatus was slit-like and vertically oriented in 48(92.3%) patients who had
      undergone TIP repair. Conclusion. The Snodgrass repair is significantly faster,
      with more natural cosmetic appearance of the meatus than the Mathieu's repair. 

PMID- 24944835
TI  - Outcomes of dorsal and ventral buccal graft urethroplasty at a tertiary hospital
      in Uganda.
AB  - Purpose. Although the use of buccal mucosa in substitution urethroplasty has been
      practiced for some years, it has not been free of controversy over which surgical
      technique is the most appropriate to use. There is paucity of data in Sub-Saharan
      Africa about its success; this study presents the outcomes of dorsal and ventral
      buccal graft urethroplasty at a sub-Saharan tertiary hospital. Methods. This is a
      prospective study in which buccal mucosa was used for ventral and dorsal grafts;
      followup was up to two years. All patients provided informed written consent for
      the procedures. Results. Seventy-two patients with bulbar urethral strictures
      underwent buccal graft one-stage urethroplasty. Mean age was 55 years; etiology
      of the strictures was postinflammatory due to urethritis from sexually
      transmitted infections 97% (70/72) and trauma 3% (2/72). Buccal mucosa grafts
      were harvested from the cheek using a two-team approach. Grafts were placed on
      the ventral and dorsal urethral surfaces in 32 and 40 cases, respectively; the
      success rate was 84 and 80%, respectively. Repeated urethroplasty was
      successfully done among 10% (7/72) and patients reported resolution of symptoms
      in the follow-up period. Conclusion. There was no difference between dorsal and
      ventral onlay buccal graft outcomes for bulbar urethral strictures. The success
      rate was 80 to 84%. 

PMID- 24944837
TI  - Formulation development and optimization of fast dissolving tablets of
      aceclofenac using natural superdisintegrant.
AB  - The current research work involves preparation of fast dissolving tablets of
      Aceclofenac by direct compression method using different concentrations of
      Lepidium sativum mucilage as natural superdisintegrant. A two-factor three-level
      (3(2)) factorial design is being used to optimize the formulation. Nine
      formulation batches (D1-D9) were prepared accordingly. Two factors as independent
      variables (X 1-amount of beta-cyclodextrin and X 2-amount of Lepidium sativum
      mucilage) were taken with three levels (+1, 0, -1). The levels of two factors
      were selected on the basis of preliminary experiments conducted and their effect
      on three dependent variables (disintegration time, wetting time, and in vitro
      drug release) was studied along with their % prediction error. All the active
      blends were evaluated for postcompression parameters (angle of repose, Carr's
      index, Hausner ratio, etc.) and the tablets were evaluated for postcompression
      parameters (weight variation, hardness, and friability, wetting time,
      disintegration time, water absorption ratio, and in vitro drug release studies).
      The optimum batch was further used for SEM and stability studies. Formulation D5
      was selected by the Design-Expert software which exhibited DT (15.5 sec), WT
      (18.94 sec), and in vitro drug release (100%) within 15 minutes. 

PMID- 24944838
TI  - Physiological Constants of the Entomopathogenic Bacterium Xenorhabdus nematophila
      Determined by Microbial Growth Kinetics.
AB  - Xenorhabdus nematophila, an entomopathogenic bacterium that symbiotically
      associates with the entomoparasitic nematode Steinernema carpocapsae, was studied
      to determine its physiological parameters of glucose utilization. X. nematophila
      was cultured in chemically defined media containing various concentrations of
      glucose under optimal conditions utilizing a two-liter fermentation system.
      Specific growth rates were obtained from each glucose batch. Specific growth
      rates and their associated glucose concentrations were used to determine
      physiological parameters. These parameters include the bacterium's substrate
      utilization constant (K s ) and its maximum specific growth rate (MU max). The
      bacteria exhibited a K s value of 2.02 mg/L suggesting that X. nematophila has a
      high affinity for glucose. The MU max of Xenorhabdus was determined to be 1.03 h(
      1). Further research is needed to determine if microbial affinities to different
      substrates have any influence on biological relationships (symbiosis,
      pathogenicity, parasitism, etc.) between prokaryotes and higher organisms. 

PMID- 24944836
TI  - Does Male Circumcision Protect against Sexually Transmitted Infections? Arguments
      and Meta-Analyses to the Contrary Fail to Withstand Scrutiny.
AB  - We critically evaluate a recent article by Van Howe involving 12 meta-analyses
      that concludes, contrary to current evidence, that male circumcision increases
      the risk of various common sexually transmitted infections (STIs). Our detailed
      scrutiny reveals that these meta-analyses (1) failed to include results of all
      relevant studies, especially data from randomized controlled trials, (2)
      introduced bias through use of inappropriate control groups, (3) altered original
      data, in the case of human papillomavirus (HPV), by questionable adjustments for
      "sampling bias," (4) failed to control for confounders through use of crude odds
      ratios, and (5) used unnecessarily complicated methods without adequate
      explanation, so impeding replication by others. Interventions that can reduce the
      prevalence of STIs are important to international health. Of major concern is the
      global epidemic of oncogenic types of HPV that contribute to the burden of
      genital cancers. Meta-analyses, when well conducted, can better inform public
      health policy and medical practice, but when seriously flawed can have
      detrimental consequences. Our critical evaluation leads us to reject the findings
      and conclusions of Van Howe on multiple grounds. Our timely analysis thus
      reaffirms the medical evidence supporting male circumcision as a desirable
      intervention for STI prevention. 

PMID- 24944839
TI  - Antibiotic Resistance Pattern and Evaluation of Metallo-Beta Lactamase Genes
      Including bla- IMP and bla- VIM Types in Pseudomonas aeruginosa Isolated from
      Patients in Tehran Hospitals.
AB  - Beta-lactamase producing strains of Pseudomonas aeruginosa are important
      etiological agents of hospital infections. Carbapenems are among the most
      effective antibiotics used against Pseudomonas infections, but they can be
      rendered infective by group B beta -lactamase, commonly called metallo-beta
      lactamase. In this study, the antimicrobial sensitivity patterns of P. aeruginosa
      strains isolated from 9 different hospitals in Tehran, Iran, as well as the
      prevalence of MBLs genes (bla- VIM and bla- IMP ) were determined. A total of 212
      strains of P. aeruginosa recovered from patients in hospitals in Tehran were
      confirmed by both biochemical methods and PCR. Their antimicrobial sensitivity
      patterns were determined by Kirby-Bauer disk diffusion method. Following MIC
      determination, imipenem resistant strains were selected by DDST method which was
      followed by PCR tests for determination of MBLs genes: bla- IMP and bla- VIM .
      The results indicated that, in the DDST phenotypic method, among the 100 imipenem
      resistant isolates, 75 strains were MBLs positive. The PCR test indicated that 70
      strains (33%) carried bla- VIM gene and 20 strains (9%) harbored bla- IMP . The
      results indicated that the extent of antibiotic resistance among Pseudomonas
      aeruginosa is on the rise. This may be due to production of MBLs enzymes.
      Therefore, determination of antibiotic sensitivity patterns and MBLs production
      by these bacteria, can be important in control of clinical Pseudomonas infection.

PMID- 24944841
TI  - The Relationship between High Risk for Obstructive Sleep Apnea and General and
      Central Obesity: Findings from a Sample of Chilean College Students.
AB  - This cross-sectional study evaluates the prevalence and extent to which high risk
      for obstructive sleep apnea (OSA) is associated with general obesity and central
      obesity among college students in Punta Arenas, Chile. Risk for OSA was assessed
      using the Berlin Questionnaire and trained research nurses measured
      anthropometric indices. Overweight was defined as body mass index (BMI) of 25
      29.9 kg/m(2) and general obesity was defined as BMI >= 30 kg/m(2). Central
      obesity was defined as waist circumference >=90 centimeters (cm) for males and
      >=80 cm for females. Multivariate logistic regression models were fit to obtain
      adjusted odds ratios (OR) and 95% confidence intervals (CI). Prevalence of high
      risk for OSA, general obesity, and central obesity were 7.8%, 12.8%, and 42.7%,
      respectively. Students at high risk for OSA had greater odds of general obesity
      (OR 9.96; 95% CI: 4.42-22.45) and central obesity (OR 2.78; 95% CI 1.43-5.40).
      Findings support a strong positive association of high risk for OSA with obesity.

PMID- 24944843
TI  - Imported zika virus infection from the cook islands into australia, 2014.
AB  - A female resident of Townsville, Queensland, Australia has been diagnosed with
      Zika virus infection following a recent trip to the Cook Islands. An initial
      serum sample collected in March, 2014 was positive by two separate Zika virus
      TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and
      phylogenetics of the complete Cook Islands Zika virus envelope gene revealed
      99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage.
      In addition, IgG and IgM antibody seroconversions were detected between paired
      acute and convalescent phase sera using recombinant Zika virus serology assays.
      This is the first known imported case of Zika virus infection into northern
      Queensland where the potential mosquito vector Aedes aegypti is present and only
      the second such reported case diagnosed within Australia.

PMID- 24944842
TI  - Glycogen Synthase Kinase 3beta in Pancreatic Cancer and its Implications in
      Chemotherapy and Radiation Therapy.
AB  - Pancreatic cancer is a highly lethal disease with a poor prognosis characterized
      by local and systemic disease progression. Both radiation and chemotherapy play
      important roles in the management of this disease. However, in order to improve
      standard therapy many molecularly targeted agents are being developed. Glycogen
      synthase kinase 3beta (GSK3beta) participates in a multitude of cellular
      processes and is a newly proposed therapeutic target in pancreatic cancer. This
      review will discuss both the oncogenic and tumor suppressor functions of GSK3beta
      in pancreatic cancer with an emphasis on the roles of GSK3beta in tumor cell
      survival and sensitivity to radiation and chemotherapy.

PMID- 24944840
TI  - Protein biomarkers of periodontitis in saliva.
AB  - Periodontitis is a chronic inflammatory condition of the tissues that surround
      and support the teeth and is initiated by inappropriate and excessive immune
      responses to bacteria in subgingival dental plaque leading to loss of the
      integrity of the periodontium, compromised tooth function, and eventually tooth
      loss. Periodontitis is an economically important disease as it is time-consuming
      and expensive to treat. Periodontitis has a worldwide prevalence of 5-15% and the
      prevalence of severe disease in western populations has increased in recent
      decades. Furthermore, periodontitis is more common in smokers, in obesity, in
      people with diabetes, and in heart disease patients although the pathogenic
      processes underpinning these links are, as yet, poorly understood. Diagnosis and
      monitoring of periodontitis rely on traditional clinical examinations which are
      inadequate to predict patient susceptibility, disease activity, and response to
      treatment. Studies of the immunopathogenesis of periodontitis and analysis of
      mediators in saliva have allowed the identification of many potentially useful
      biomarkers. Convenient measurement of these biomarkers using chairside analytical
      devices could form the basis for diagnostic tests which will aid the clinician
      and the patient in periodontitis management; this review will summarise this
      field and will identify the experimental, technical, and clinical issues that
      remain to be addressed before such tests can be implemented. 

PMID- 24944844
TI  - Barriers to Trace-back in a Salad-associated EHEC Outbreak, Sweden, June 2013.
AB  - In June-July 2013, six counties notified the Swedish Institute for Communicable
      Disease Control of enterohaemorrhagic E.coli (EHEC) infections among attendees at
      a hotel in Dalarna, Sweden. An outbreak control team investigated to identify the
      source and implement control measures. We included individuals who attended the
      hotel between June 19th-25th in a cohort. We asked them about animal contact,
      swimming, and consumption of food items during this time using a questionnaire. A
      confirmed case was an EHEC O157:H7 outbreak strain positive individual who
      developed abdominal pain or diarrhoea between June 20th-July 2nd. We described
      the outbreak in time, place and person, calculated risk ratios (RR) and 95%
      confidence intervals (CI). We investigated the kitchen, tested and traced back
      implicated food items. 172 individuals responded. We identified 19 confirmed
      cases (Median age: 17 years, 64% female) with symptom onset between June 22nd
      27th. Eating green salad on June 20th was associated with illness (RR:3.7;CI:1.3
      11). The kitchen mixed green salads without records and destroyed leftovers
      immediately. Hence we could not conduct trace-back or obtain microbiological
      confirmation. Green salad contaminated before entering the kitchen was the likely
      outbreak source. We recommended early collaboration with food agencies and better
      restaurant records to facilitate future investigations. 

PMID- 24944845
TI  - Reweaving the tapestry: a supertree of birds.
AB  - Our knowledge of the avian tree of life remains uncertain, particularly at deeper
      levels due to the rapid diversification early in their evolutionary history. They
      are the most abundant land vertebrate on the planet and have been of great
      historical interest to systematists. Birds are also economically and ecologically
      important and as a result are intensively studied, yet despite their importance
      and interest to humans around 13% of taxa currently on the endangered species
      list perhaps as a result of human activity. Despite all this no comprehensive
      phylogeny that includes both extinct and extant species currently exists. Here we
      present a species-level supertree, constructed using the Matrix Representation
      with Parsimony method, of Aves containing approximately two thirds of all species
      from nearly 1000 source phylogenies with a broad taxonomic coverage. The source
      data for the tree were collected and processed according to a strict protocol to
      ensure robust and accurate data handling. The resulting tree topology is largely
      consistent with molecular hypotheses of avian phylogeny. We identify areas that
      are in broad agreement with current views on avian systematics and also those
      that require further work. We also highlight the need for leaf-based support
      measures to enable the identification of rogue taxa in supertrees. This is a
      first attempt at a supertree of both extinct and extant birds, it is not intended
      to be utilised in an overhaul of avian systematics or as a basis for taxonomic re
      classification but provides a strong basis on which to base further studies on
      macroevolution, conservation, biodiversity, comparative biology and character
      evolution, in particular the inclusion of fossils will allow the study of bird
      evolution and diversification throughout deep time. 

PMID- 24944846
TI  - Assessing the origin of and potential for international spread of chikungunya
      virus from the Caribbean.
AB  - BACKGROUND: For the first time, an outbreak of chikungunya has been reported in
      the Americas. Locally acquired infections have been confirmed in fourteen
      Caribbean countries and dependent territories, Guyana and French Guiana, in which
      a large number of North American travelers vacation. Should some travelers become
      infected with chikungunya virus, they could potentially introduce it into the
      United States, where there are competent Aedes mosquito vectors, with the
      possibility of local transmission. METHODS: We analyzed historical data on
      airline travelers departing areas of the Caribbean and South America, where
      locally acquired cases of chikungunya have been confirmed as of May 12th, 2014.
      The final destinations of travelers departing these areas between May and July
      2012 were determined and overlaid on maps of the reported distribution of Aedes
      aeygpti and albopictus mosquitoes in the United States, to identify potential
      areas at risk of autochthonous transmission. RESULTS: The United States alone
      accounted for 52.1% of the final destinations of all international travelers
      departing chikungunya indigenous areas of the Caribbean between May and July
      2012. Cities in the United States with the highest volume of air travelers were
      New York City, Miami and San Juan (Puerto Rico). Miami and San Juan were high
      travel-volume cities where Aedes aeygpti or albopictus are reported and where
      climatic conditions could be suitable for autochthonous transmission. CONCLUSION:
      The rapidly evolving outbreak of chikungunya in the Caribbean poses a growing
      risk to countries and areas linked by air travel, including the United States
      where competent Aedes mosquitoes exist. The risk of chikungunya importation into
      the United States may be elevated following key travel periods in the spring,
      when large numbers of North American travelers typically vacation in the
      Caribbean.

PMID- 24944847
TI  - Consistency of clinical biomechanical measures between three different
      institutions: implications for multi-center biomechanical and epidemiological
      research.
AB  - PURPOSE/BACKGROUND: Multi-center collaborations provide a powerful alternative to
      overcome the inherent limitations to single-center investigations. Specifically,
      multi-center projects can support large-scale prospective, longitudinal studies
      that investigate relatively uncommon outcomes, such as anterior cruciate ligament
      injury. This project was conceived to assess within- and between-center
      reliability of an affordable, clinical nomogram utilizing two-dimensional video
      methods to screen for risk of knee injury. The authors hypothesized that the two
      dimensional screening methods would provide good-to-excellent reliability within
      and between institutions for assessment of frontal and sagittal plane
      biomechanics. METHODS: Nineteen female, high school athletes participated. Two
      dimensional video kinematics of the lower extremity during a drop vertical jump
      task were collected on all 19 study participants at each of the three facilities.
      Within-center and between-center reliability were assessed with intra- and inter
      class correlation coefficients. RESULTS: Within-center reliability of the
      clinical nomogram variables was consistently excellent, but between-center
      reliability was fair-to-good. Within-center intra-class correlation coefficient
      for all nomogram variables combined was 0.98, while combined between-center inter
      class correlation coefficient was 0.63. CONCLUSIONS: Injury risk screening
      protocols were reliable within and repeatable between centers. These results
      demonstrate the feasibility of multi-site biomechanical studies and establish a
      framework for further dissemination of injury risk screening algorithms.
      Specifically, multi-center studies may allow for further validation and
      optimization of two-dimensional video screening tools. LEVEL OF EVIDENCE: 2b.

PMID- 24944849
TI  - The activity pattern of the lumbo-pelvic muscles during prone hip extension in
      athletes with and without hamstring strain injury.
AB  - BACKGROUND: Altered muscular activation pattern has been associated with
      musculoskeletal disorders. Some previous studies have demonstrated muscle
      weakness or tightness in athletes who have sustained hamstring (HAM) injuries.
      However, no study has clinically investigated the muscular activity pattern in
      subjects with HAM strain injuries. OBJECTIVE: To investigate the activity pattern
      of the ipsilateral erector spinae (IES), contralateral erector spinae (CES),
      gluteus maximus (GM), and medial and lateral HAM muscles during the prone hip
      extension (PHE) test in athletes with and without history of HAM strain injury.
      DESIGN: Cross-sectional non-experimental study design. PARTICIPANTS: A
      convenience sample of 20 soccer athletes participated in the study. Subjects were
      categorized into two groups: those with history of HAM strain injury (n=10, mean
      age = 22.6 +/- 3.74) and without history of HAM strain (n =10, mean age = 22.45
      +/- 3.77). METHODS: Three repetitions of the PHE were performed by each subject,
      and the electromyographic (EMG) outputs of the IES, CES, GM, and HAM muscles were
      recorded, processed and normalized to maximum voluntary electrical activity
      (MVE). Independent t-tests were used for comparing activation means of each
      muscle between athletes with and without history of HAM strain injury. RESULTS:
      There were significant differences in EMG activity of the GM (p= 0.04) and medial
      HAM (p = 0.01) between two groups. No significant difference was found in EMG
      signals of the IES (p= 0.26), CES (= 0.33) and lateral HAM (p= 0.58) between the
      two groups. Greater although non-significant normalized EMG outputes of IES, CES
      and lateral HAM were seen in athletes with history of HAM strain compared to
      those without HAM strain. CONCLUSION: The findings of this study demonstrated
      greater normalized EMG activity of GM and medial HAM tested in athletes with
      history of HAM strain compared to those without HAM strain (altered activation
      pattern). LEVEL OF EVIDENCE: 3a.

PMID- 24944848
TI  - Effect of fatigue on landing performance assessed with the landing error scoring
      system (less) in patients after ACL reconstruction. A pilot study.
AB  - BACKGROUND: Fatigue has been shown to affect performance of hop tests in patients
      after anterior cruciate ligament reconstruction (ACLR) compared to uninjured
      controls (CTRL). This may render the hop test less sensitive in detecting landing
      errors. The primary purpose of this study was to investigate the effect of lower
      extremity fatigue on landing performance assessed with the Landing Error Scoring
      System (LESS) in patients after ACLR compared to a CTRL group. It is plausible
      that fatigue would have an effect on confidence and risk appraisal in the ACLR
      group. The secondary purpose was to determine the relationship between
      psychological responses and LESS scores after fatigue. METHODS: Twelve patients
      following ACLR (6 males, 6 females) who were tested at 10 +/- 2.4 months after
      surgery participated in the current study and were compared to 10 subjects in the
      control group (5 males, 5 females). Subjects performed a jump-landing task and
      the landing was assessed using the Landing Error Scoring System (LESS) both
      before and after fatigue. Digital video camcorders recorded frontal and sagittal
      plane views of the subject performing the task. The LESS was scored using video
      replay. Psychological responses in the ACLR group were assessed with the ACL-RSI
      questionnaire. RESULTS: Patients after ACLR had a median LESS of 6.5 which
      reflects a poor result (LESS >6) in the pre-fatigue condition compared to
      controls who had a LESS of 2.5 which is considered excellent (<=4). In the post
      fatigue condition, median LESS in patients after ACLR increased to 7.0 whereas in
      the control group the LESS increased to 6.0 both of which reflect a poor result.
      The median increase in LESS was larger in the control (2.0) group compared to
      patients after ACLR (1.0) but the difference was not significant (p=0.165).
      CONCLUSIONS: Patients after ACLR have higher LESS scores at baseline compared to
      a control group. Fatigue resulted in an increase in scores on the LESS in both
      groups. LEVEL OF EVIDENCE: 3b.

PMID- 24944850
TI  - Association between quadriceps strength and self-reported physical activity in
      people with knee osteoarthritis.
AB  - PURPOSE/BACKGROUND: Physical inactivity is common in patients with knee
      osteoarthritis (OA) and has been linked to serious comorbidities such as
      cardiovascular disease, obesity, and diabetes. The purpose of this study was to
      examine the association between quadriceps strength and self-reported physical
      activity in patients with radiographically confirmed knee OA. Secondarily, the
      authors' sought to determine if there were differences in quadriceps strength
      between knee OA patients with low physical activity (LPA) and knee OA patients
      with higher physical activity (HPA). A tertiary aim of this study was to examine
      the effect of gender on physical activity and quadriceps strength in patients
      with knee OA. METHODS: Thirty-six patients with radiographically diagnosed
      tibiofemoral knee OA participated (15 males, 21 females; age = 59.9+/-11.6 yrs;
      height = 171.2+/-9.2 cm; mass = 84.3+/-18.9 kg; body mass index (BMI)= 28.9+/
      6.9;Godin Leisure-Time questionnaire =32.5+/-25.01). Maximal isometric knee
      extensor strength was assessed with a Isokinetic dynamometer in 70 degrees  of
      knee flexion. Knee extension torque values were normalized to body mass (Nm(*)kg(
      1)). Physical activity was evaluated using the Godin Leisure-Time questionnaire.
      A Godin-Leisure time score of 32.5, which was the mean score in the current
      dataset, was what was used to categorize subjects into LPA and HPA subgroups.
      Independent t-tests were used to determine differences in strength between HPA
      and LPA subgroups, as well as differences in strength and physical activity
      between genders. Pearson Product Moment and Spearman rank correlations were used
      to analyze associations between normally and non-normally distributed variables.
      RESULTS: Quadriceps strength was positively correlated with physical activity
      (r=0.44, r(2)=0.18, p=0.01). The HPA subgroup had significantly greater
      quadriceps strength (n=15, 2.01+/-0.84) compared to the LPA subgroup (n=21, 1.5+/
      0.59, p=0.04). Strength was significantly correlated with physical activity in
      the HPA subgroup (rho=0.53, p=0.04), but not in the LPA subgroup (rho=
      0.21,p=0.35). Males reported significantly more physical activity (43.0+/-28.5 vs
      25.1+/-19.64; p=0.03) and greater strength than females in the entire cohort
      (2.15+/-0.73 Nm(*)kg(-1) vs 1.40+/-0.57 Nm(*)kg(-1); p= 0.002), and the HPA
      subgroup (2.4+/-0.65 Nm(*)kg(-1) vs 1.4+/- 0.68 Nm(*)kg(-1); P=0.02). There were
      no gender differences for strength in the LPA subgroup. CONCLUSION: Higher levels
      of quadriceps strength correlate with higher physical activity in knee OA
      patients. The association between higher strength and increased physical activity
      is stronger in the HPA subgroup compared to the entire sample. Additionally, the
      HPA subgroup demonstrated greater quadriceps strength compared to the LPA
      subgroup. LEVEL OF EVIDENCE: 3.

PMID- 24944851
TI  - Activation deficits do not limit quadriceps strength training gains in patients
      after total knee arthroplasty.
AB  - PURPOSE/BACKGROUND: Patients after total knee arthroplasty (TKA) are known to
      exhibit deficits in quadriceps muscle activation. The purpose of this study was
      to determine if quadriceps activation levels in patients after TKA at the
      beginning of rehabilitation would influence quadriceps strength after
      rehabilitation. DESIGN: A secondary analysis of data from a prospective,
      randomized, longitudinal clinical trial. SETTING: Institutional clinic and
      research laboratory. PARTICIPANTS: Patients who underwent unilateral TKA (Men=
      102; Female= 84). MAIN OUTCOME: Voluntary activation of the quadriceps during
      maximal voluntary isometric contractions (MVIC) was measured using the central
      activation ratio (CAR). Hierarchical multivariate regression analysis was used to
      determine if CAR prior to treatment could predict MVIC after the strength
      training intervention. RESULTS: After controlling for age, sex, and initial
      strength levels (R(2)= 0.548; p<0.001), the predictability of quadriceps strength
      after the 6-week intervention did not change when pain during MVIC (R(2)= 0.551;
      p= 0.317) and pre-rehabilitation activation levels (R(2)= 0.551; p= 0.818) were
      introduced into the regression. CONCLUSIONS: Initial quadriceps activation
      levels, for patients who underwent TKA, did not predict the quadriceps strength
      following a strength training intervention. Therefore, deficits in voluntarily
      activation post-operatively should not be considered as a rate-limiting factor in
      recovering quadriceps strength after TKA. LEVEL OF EVIDENCE: Retrospective cohort
      study. Level IIb.

PMID- 24944852
TI  - Running more than three kilometers during the first week of a running regimen may
      be associated with increased risk of injury in obese novice runners.
AB  - BACKGROUND: Training guidelines for novice runners are needed to reduce the risk
      of injury. The purpose of this study was to investigate whether the risk of
      injury varied in obese and non-obese individuals initiating a running program at
      different weekly distances. METHODS: A volunteer sample of 749 of 1532 eligible
      healthy novice runners was included in a 3-week observational explorative
      prospective cohort study. Runners were categorized into one of six strata based
      on their body mass index (BMI) (<=30=low; >30=high) and running distance after 1
      week (<3 km = low; 3 to 6 km = medium; >6 km = high). Data was collected for
      three weeks for the six strata. The main outcome measure was running-related
      injury. RESULTS: Fifty-six runners sustained a running-related injury during the
      3-week data collection. A significantly greater number of individuals with BMI>30
      sustained injuries if they ran between 3 to 6 km (cumulative risk difference
      (CRD) = 14.3% [95%CI: 3.3% to 25.3%], p<0.01) or more than 6 km (CRD = 16.2%
      [95%CI: 4.4% to 28.0%], p<0.01) the first week than individuals in the reference
      group (low distance and low BMI). The effect-measure modification between high
      running distance and BMI on additive scale was positive (11.7% [-3.6% to 27.0%],
      p=0.13). The number of obese individuals needed to change their running distance
      from high to low to avoid one injury was 8.5 [95%CI: 4.6 to 52]. CONCLUSIONS:
      Obese individuals were at greater risk of injury if they exceeded 3 km during the
      first week of their running program. Because of a considerable injury risk
      compared with their non-obese peers, individuals with a BMI>30 may be well
      advised to begin running training with an initial running distance of less than 3
      km (1.9 miles) the first week of their running regime. Large-scale trials are
      needed to further describe and document this relationship. LEVEL OF EVIDENCE:
      Level 2b.

PMID- 24944853
TI  - A speed distance-based classification system for injury prevention and research
      in international and domestic youth baseball players.
AB  - BACKGROUND: An objective classification system for studying youth baseball
      players in the U.S.A. was published in 1996. Professional baseball is composed of
      greater than 25% international players a majority of whom come from five
      countries. Many youth baseball players are injured in early years play, both in
      the U.S.A. and internationally. There is no international classification system
      to study youth baseball pitching injuries, biomechanics, or maturation, but one
      is needed in order to compare and combine pitchers in multi-center studies.
      Uniform domestic and international pre-injury normative data is optimum. Ideally,
      data collection should be practical requiring inexpensive equipment and limited
      time demands. HYPOTHESIS: The mathematical model, developed in 1996 on 853 boys
      and validated on 114 boys in the Mid-Atlantic Region, U.S.A., is internationally
      applicable, allowing easy classification of youth baseball pitchers and levels
      throughout the world. METHODS: Seven-hundred-twenty-one international pitchers,
      ages 8-14, threw five full-speed pitches recorded with a calibrated radar gun and
      four maximum distance throws on a marked field. Demographics included age,
      height, weight, and years pitched. Collection sites included foreign national
      baseball clubs (Dominican Republic, Venezuela, Puerto Rico, Japan and the
      Philippines), the Mexican national youth tournament, and a multinational
      tournament (Brazil, Peru and Colombia). The mathematical model developed in 1996
      was used to generate predicted distances for this sample for comparison with
      actual distances. In addition to the overall analysis, adequate sample sizes were
      available for comparing predicted and actual distances by country for four of the
      countries. RESULTS: The correlation between predicted distance using the
      mathematical model and actual distance was 0.90. The mean of the international
      players was 1-2 standard deviations above the USA mean for speed and one standard
      deviation above the mean for distance. There was no systematic over or under
      prediction indicating that both relative and absolute fit for the model was
      excellent. CONCLUSIONS: The mathematical model developed in 1996 on U.S.A.
      baseball players is robustly generalizable to international youth baseball
      pitchers. CLINICAL RELEVANCE: Pre-injury distance/speed data allows for
      classification of youth baseball player of multiple levels between the ages of 8
      14. International and regional comparisons are now possible for multi-center
      studies in order to better define risk factors, compare studies, and combine data
      based upon pre-injury maximum long toss data. Data collection requires only a
      field, a few balls, and a tape measure.

PMID- 24944854
TI  - Lower extremity balance is improved at time of return to throwing in baseball
      players after an ulnar collateral ligament reconstruction when compared to pre
      operative measurements.
AB  - BACKGROUND: / PURPOSE: Lower extremity balance deficits have been shown to lead
      to altered kinematics and increased injury risk in lower extremity athletes. The
      purpose of this study was to compare lower extremity balance in baseball players
      with an ulnar collateral ligament (UCL) tear pre-operatively and post-operatively
      at the beginning of the pre-return to throwing program stage of rehabilitation (3
      months). METHODS: Thirty-three competitive high school and collegiate male
      baseball players (18.5 +/- 3.2) with a diagnosed UCL tear volunteered for the
      study. Of the 33 baseball players 29 were pitchers, 1 was a catcher, and 3 were
      infielders. Participants were seen pre-operatively and at 3 months post
      operatively. This 3 month point was associated with a follow-up visit to the
      orthopedic surgeon and subsequent release to begin the pre-return to throwing
      mark for baseball players following their surgery. Following surgery, each
      participant followed a standard UCL protocol which included focused lower
      extremity balance and neuromuscular control exercises. Participants were tested
      for single leg balance using the Y-Balance TestTM - Lower Quadrant (YBT-LQ) on
      both their lead and stance limbs. YBT-LQ composite scores were calculated for the
      stance and lead limbs pre- and post-operatively and compared over time. Paired t
      tests were used to calculate differences between time 1 and time 2 (p < 0.05).
      RESULTS: Baseball players with diagnosed UCL tears demonstrated significant
      balance deficits on their stance (p < .001) and lead (p = .009) limbs prior to
      surgery compared to balance measures at the 3-month follow up (Stance Pre-Op =
      89.4 +/- 7.5%; Stance 3 Month = 94.9 +/- 9.5%) (Lead Pre-Op = 90.2 +/- 6.7%; Lead
      3 Month = 93.6 +/- 7.2%). CONCLUSION: Based on the results of this study, lower
      extremity balance is altered in baseball players with UCL tears prior to surgery.
      Statistically significant improvements were seen and balance measures improved at
      the time of return to throwing. LEVEL OF EVIDENCE: Level 2b.

PMID- 24944855
TI  - Clinical outcomes of the addition of eccentrics for rehabilitation of previously
      failed treatments of golfers elbow.
AB  - INTRODUCTION AND PURPOSE: Eccentric training of the wrist extensors has been
      shown to be effective in treating chronic lateral epicondylosis. However, its
      efficacy in the treatment of medial epicondylosis has yet to be demonstrated. The
      objective of this study was to assess the effectiveness of a novel eccentric
      wrist flexor exercise added to standard treatment for chronic medial
      epicondylosis in patients who did not respond to previous therapeutic
      interventions for this disorder. NUMBER OF SUBJECTS: 20. MATERIALS/METHODS:
      Patients (13 men, 7 women; age 49+/-12 yr) with chronic medial epicondylosis who
      had failed previous treatment for this disorder (physical therapy 7, cortisone
      injection 7, PRP 1, NSAIDS 15) were prescribed isolated eccentrics in addition to
      wrist stretching, ultrasound, cross-friction massage, heat and ice. The specific
      isolated eccentric wrist flexor strengthening exercise performed by the patients
      involved twisting a rubber bar (Flexbar, Hygenic Corportation, Akron OH) with
      concentric wrist flexion of the noninvolved arm and releasing the twist by
      eccentrically contracting the wrist flexors of the involved arm (3 * 15 twice
      daily). A DASH questionnaire was recorded at baseline and again after the
      treatment period. Treating clinicians were blinded to baseline DASH scores.
      Treatment effect was assessed using paired t-test. Based on previous work it was
      estimated that with a sample of 20 patients there would be 80% power to detect a
      13 point improvement in DASH scores (p<.05). RESULTS: The pathology was in the
      dominant arm of 18 patients and recurrent in 10. Primary symptomatic activities
      were golf (14), tennis (2), basketball (1), weight lifting (1), and general
      activities of daily living (2). There was a significant improvement in outcomes
      following the addition of isolated eccentrics (Pre DASH 34.7+/-16.2 vs. Post DASH
      7.9+/-11.1, p<.001). For the 18 patients involved in sports, the sports module of
      the DASH score improved from 73.9+/-28.9 to 13.2+/-25.0, p<.001). Physical
      therapy visits ranged from 1-22 with an average of 12+/-6 and, average treatment
      duration of 6.1+/-2.5 wks (range 1-10). Home exercise program compliance was
      recorded for each subject (15 full, 3 mostly, 1 occasionally, 1 none).
      CONCLUSIONS: The outcome measure for chronic medial epicondylosis was markedly
      improved with the addition of an eccentric wrist flexor exercise to standard
      physical therapy. Given the inconsistent outcomes for patients previously treated
      with chronic medial epicondylosis the addition of isolated eccentrics seems
      warranted based on the results of this study. CLINICAL RELEVANCE: This novel
      exercise, using an inexpensive rubber bar, provides a practical means of adding
      isolated eccentric training to the treatment of chronic medial epicondylosis.
      LEVEL OF EVIDENCE: 2b.

PMID- 24944856
TI  - Diagnosis and expedited surgical intervention of a complete hamstring avulsion in
      a military combatives athlete: a case report.
AB  - BACKGROUND AND PURPOSE: Hamstring injuries are frequent injuries in athletes,
      with the most common being strains at the musculotendinous junction or within the
      muscle belly. Conversely, hamstring avulsions are rare and often misdiagnosed
      leading to delay in appropriate surgical interventions. The purpose of this case
      report is to describe the history and physical examination findings that led to
      appropriate diagnostic imaging and the subsequent diagnosis and expedited
      surgical intervention of a complete avulsion of the hamstring muscle group from
      the ischium in a military combatives athlete. CASE DESCRIPTION: The patient was a
      25 year-old male who sustained a hyperflexion injury to his right hip with knee
      extension while participating in military combatives, presenting with acute
      posterior thigh and buttock pain. History and physical examination findings from
      a physical therapy evaluation prompted an urgent magnetic resonance imaging (MRI)
      study, which led to the diagnosis of a complete avulsion of the hamstring muscle
      group off the ischium. OUTCOME: Expedited surgical intervention occurred within
      13 days of the injury potentially limiting comorbidities associated with delayed
      diagnosis. CONCLUSION: Recognition of the avulsion led to prompt surgical
      evaluation and intervention. Literature has shown that diagnosis of hamstring
      avulsions are frequently missed or delayed, which results in a myriad of
      complications. LEVEL OF EVIDENCE: Level 4.

PMID- 24944857
TI  - Upper extremity deep venous thromboembolism following arthroscopic labral repair
      of the shoulder and biceps tenodesis: a case report.
AB  - STUDY DESIGN: Case Report. BACKGROUND: Upper extremity deep vein thrombosis
      (UEDVT) is a rare complication following arthroscopic shoulder surgery. However,
      it is possible that a patient with an UEDVT will present to physical therapy as
      the first service to interact with the patient following surgery. As a result,
      proper screening in the physical therapy setting is essential. CASE DESCRIPTION:
      The purpose of this report is to present the case of a 37 year-old male who
      developed an upper extremity deep vein thrombosis (UEDVT) following arthroscopic
      glenohumeral labral repair and arthroscopically assisted biceps tenodesis. This
      patient presented with disproportionate pain and swelling of his involved upper
      extremity at his initial evaluation in physical therapy (8 days post
      operatively), which raised the index of suspicion for an UEDVT. OUTCOME: The
      patient was referred to the emergency department for immediate diagnostic testing
      and treatment. A Doppler scan provided a definitive diagnosis of UEDVT. Following
      successful medical treatment with anti-coagulant therapy, the patient went on to
      complete an otherwise uneventful course of rehabilitation. DISCUSSION: UEDVT
      events following arthroscopy are rare, and are often attributed to a systemic
      secondary stimulus. UEDVT following shoulder arthroscopy is a complication that
      occurs in the orthopaedic setting, but may present primarily to the physical
      therapist, and as such requires awareness of its clinical presentation and
      treatment. Care of UEDVT requires a systems-based approach when considering
      clinical manifestation, best treatment, and future research.

PMID- 24944858
TI  - Management of acute shoulder pain in an adolescent lacrosse athlete: a case
      report.
AB  - Acute onset of shoulder pain in adolescent athletes typically is related to
      trauma. The subject of this case report, a 13 year-old male, was injured when he
      collided with another athlete while his right arm was extended. He experienced
      immediate onset of significant right shoulder pain. Manual assessment in the
      emergency department revealed anterior tenderness and loss of function due to
      pain - most notably limitations in both active internal rotation and abduction. A
      plain film showed a radiographic density anterior to the humeral head but a
      donation site (where a bony avulsion may have occurred) was not delineated.
      Magnetic resonance imaging clearly identified a lesser tuberosity avulsion (thus
      the site of origin of the bony material) encompassing the insertion of the
      subscapularis muscle with retraction of approximately one centimeter. Open
      surgical repair (reduction and fixation) was performed with excellent results.
      LEVEL OF EVIDENCE: 5 (Single Case report).

PMID- 24944859
TI  - Considerations and return to swim protocol for the pediatric swimmer after non
      operative injury.
AB  - Pediatric swimmers perform repetitive motions over prolonged distance that
      predisposes them to injury. There is evidence highlighting biomechanics,
      evaluation, and treatment of swimmers; however, there is minimal research related
      to return to swimming following non-operative injury other than some suggestion
      of restricted distance guidelines. The purpose of this clinical commentary is to
      discuss considerations related to the training of pediatric swimmers, as well as
      to provide clinicians with an example return to swim protocol that is sensitive
      to the multidimensional components of the pediatric swimmer's training and
      competition. LEVEL OF EVIDENCE: Level V.

PMID- 24944860
TI  - Functional movement screening: the use of fundamental movements as an assessment
      of function - part 1.
AB  - To prepare an athlete for the wide variety of activities needed to participate in
      or return to their sport, the analysis of fundamental movements should be
      incorporated into screening in order to determine who possesses, or lacks, the
      ability to perform certain essential movements. In a series of two articles, the
      background and rationale for the analysis of fundamental movement will be
      provided. The Functional Movement Screen (FMSTM) will be described, and any
      evidence related to its use will be presented. Three of the seven fundamental
      movement patterns that comprise the FMSTM are described in detail in Part I: the
      Deep Squat, Hurdle Step, and In-Line Lunge. Part II of this series which will be
      provided in the August issue of IJSPT, will provide a detailed description of the
      four additional patterns that complement those presented in Part I (to complete
      the seven total fundamental movements): Shoulder Mobility, the Active Straight
      Leg Raise, the Trunk Stability Push-up, and Rotary Stability, as well as a
      discussion about the utility of functional movement screening, and the future of
      functional movement. The intent of this two part series is to present the
      concepts associated with screening of fundamental movements, whether it is the
      FMSTM system or a different system devised by another clinician. Such a
      functional assessment should be incorporated into pre-participation screening and
      return to sport testing in order to determine whether the athlete has the
      essential movements needed to participate in sports activities at a level of
      minimum competency. LEVEL OF EVIDENCE: 5.

PMID- 24944861
TI  - Variable resistance training using elastic bands to enhance lower extremity
      strengthening.
AB  - Strengthening of the quadriceps is a central tenet of lower extremity
      rehabilitation, particularly after knee surgery. Quadriceps deficits after
      various knee procedures are well-documented. One method common to strength and
      conditioning circles is variable resistance training (VRT). VRT involves the use
      of heavy chains and elastic bands to facilitate gains in strength and power. Most
      of the application in strength training however has been on healthy, trained
      athletes. Sports physical therapists may use elastic bands for VRT to augment
      strength gains for the recovering athlete. The purpose of this manuscript is to
      provide a clinical suggestion for the use of VRT in athletic rehabilitation.
      LEVEL OF EVIDENCE: 5.

PMID- 24944863
TI  - BOLD signal and functional connectivity associated with loving kindness
      meditation.
AB  - Loving kindness is a form of meditation involving directed well-wishing,
      typically supported by the silent repetition of phrases such as "may all beings
      be happy," to foster a feeling of selfless love. Here we used functional magnetic
      resonance imaging to assess the neural substrate of loving kindness meditation in
      experienced meditators and novices. We first assessed group differences in blood
      oxygen level-dependent (BOLD) signal during loving kindness meditation. We next
      used a relatively novel approach, the intrinsic connectivity distribution of
      functional connectivity, to identify regions that differ in intrinsic
      connectivity between groups, and then used a data-driven approach to seed-based
      connectivity analysis to identify which connections differ between groups. Our
      findings suggest group differences in brain regions involved in self-related
      processing and mind wandering, emotional processing, inner speech, and memory.
      Meditators showed overall reduced BOLD signal and intrinsic connectivity during
      loving kindness as compared to novices, more specifically in the posterior
      cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior
      work and other recent neuroimaging studies of meditation. Furthermore, meditators
      showed greater functional connectivity during loving kindness between the PCC/PCu
      and the left inferior frontal gyrus, whereas novices showed greater functional
      connectivity during loving kindness between the PCC/PCu and other cortical
      midline regions of the default mode network, the bilateral posterior insula lobe,
      and the bilateral parahippocampus/hippocampus. These novel findings suggest that
      loving kindness meditation involves a present-centered, selfless focus for
      meditators as compared to novices. 

PMID- 24944864
TI  - Reducing anxiety and enhancing physical performance by using an advanced version
      of EMDR: a pilot study.
AB  - BACKGROUND: The main aim of this pilot study was to investigate an advanced
      version of eye movement desensitization and reprocessing (EMDR) for reducing
      anxiety. METHODS: Fifty participants were asked at two times of measurement (T1
      and T2 with a rest of 4 weeks) to generate anxiety via the recall of
      autobiographical memories according to their anxiety. Furthermore, the
      participants were randomly assigned to an experimental group and a control group,
      and the experimental group received an intervention of 1-2 h with the advanced
      version of EMDR in order to their anxiety 2 weeks after T1. At T1 as well as T2,
      we measured the intensity of participants' anxiety with a Likert scale (LS) and
      collected participants' state (temporary) and trait (chronic) anxiety with the
      State-Trait Anxiety Inventory (STAI). In addition, we measured participants'
      physical performance in a test for the finger musculature under the induction of
      their anxiety. RESULTS: The results showed that participant's ratings of their
      perceived intensity of anxiety (measured by a 9-point LS) and the state and trait
      anxiety decreased significantly in the experimental group but not in the control
      group from T1 to T2. Moreover, the physical performance under the induction of
      participants' anxiety increased significantly in the experimental group from T1
      to T2 and there were no significant changes in the control group. CONCLUSIONS:
      The study could show that the advanced version of EMDR is an appropriate method
      to reduce anxiety.

PMID- 24944862
TI  - Characterization of NO-producing neurons in the rat corpus callosum.
AB  - INTRODUCTION: The aim of this study was to determine the presence and
      distribution of nitric oxide (NO)-producing neurons in the rat corpus callosum
      (cc). MATERIAL AND METHODS: To investigate this aspect of cc organization we used
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry
      and neuronal NO synthase (nNOS) immunocytochemistry. RESULTS: Intense NADPH-d
      positive (NADPH-d+) neurons were found along the rostrocaudal extension of the cc
      (sagittal sections). They were more numerous in the lateral cc and gradually
      decreased in the more medial regions, where they were very few or absent. The
      Golgi-like appearance of NADPH-d+ intracallosal neurons allowed dividing them
      into five morphological types: (1) bipolar; (2) fusiform; (3) round; (4)
      polygonal; and (5) pyramidal. The number of NADPH-d+ neurons (both hemispheres)
      was counted in two brains using 50-MUm thick sections. In the first brain, counts
      involved 145 sections and neurons were 2959; in the second, 2227 neurons were
      counted in 130 sections. The distribution and morphology of nNOS-immunopositive
      (nNOSIP) neurons was identical to that of NADPH-d+neurons. Some of these neurons
      were observed in the cc ependymal region, where they might be in contact with
      cerebrospinal fluid (CSF), monitoring its composition, pH, and osmolality
      changes, or playing a role in regulating the synthesis and release of several
      peptides. The somatic, dendritic, and axonal processes of many NADPH-d+/nNOSIP
      neurons were closely associated with intracallosal blood vessels. CONCLUSIONS:
      Such close relationship raises the possibility that these neurons are a major
      source of NO during neural activity. As NO is a potent vasodilator, these
      findings strongly suggest that NO-positive neurons transduce neuronal signals
      into vascular responses in selected cc regions, thus giving rise to hemodynamic
      changes detectable by neuroimaging.

PMID- 24944865
TI  - The role of kappa opioid receptors in stress-induced reinstatement of alcohol
      seeking in rats.
AB  - INTRODUCTION: Stress is related to heavy alcohol use and relapse in alcoholics.
      Using the reinstatement model, we have shown that corticotropin-releasing factor
      (CRF) underlies stress-induced relapse to alcohol seeking in laboratory rodents.
      Little is known about how other neurotransmitters interact with CRF in these
      effects. Dynorphin and its receptor (kappa opioid receptor, KOR) are involved in
      stress responses and in alcohol seeking. KOR and CRF receptors (CRF R) may
      interact in the production of stress-related behaviors but it is not known
      whether this interaction is involved in reinstatement of alcohol seeking.
      METHODS: Male Long Evans rats were trained to self-administer alcohol (12% w/v).
      After extinction of responding, we determined the effects of the KOR agonist,
      U50,488 (2.5, 5 mg/kg) on reinstatement of alcohol seeking, and their sensitivity
      to the selective KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) (10
      mg/kg) administered at different times before U50,488. We then examined the
      effects of nor-BNI on reinstatement induced by the stressor yohimbine (1.25
      mg/kg) and on reinstatement induced by exposure to alcohol-associated cues.
      Finally, we determined whether CRF R1 blockade with antalarmin (10, 20 mg/kg)
      attenuates alcohol seeking induced by U50,488. RESULTS: U50,488 reinstated
      alcohol seeking. Prior treatment with nor-BNI 2, but not 24 h before
      administration of U50,488 or yohimbine blocked reinstatement induced by these
      drugs. Cue-induced reinstatement was blocked by nor-BNI administered 2 h prior to
      testing. Finally, U50,488-induced reinstatement was blocked by antalarmin.
      CONCLUSIONS: These data further support a role for KOR in reinstatement of
      alcohol seeking under nonstress and stressful conditions and that KOR and CRF R
      interact in these effects.

PMID- 24944866
TI  - Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic
      mechanical allodynia.
AB  - BACKGROUND: Pain constitutes the major non motor syndrome in Parkinson's disease
      (PD) and includes neuropathic pain; however current drug therapies used to
      alleviate it have only limited efficacy. This is probably due to poor
      understanding of the mechanisms underlying it. AIMS: We investigated a major
      class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a
      rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection
      was administered to produce a lesion of the nigrostriatal dopaminergic pathway.
      RESULTS AND DISCUSSION: Lesioned animals presented significant DMA in the
      orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a
      segmental implication in the neuropathic pain induced by dopamine depletion, the
      expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated
      extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the
      medullary dorsal horn (MDH). There was a high increase in PKCg expression in the
      III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2
      expression was also significantly high in the ipsilateral MDH of lesioned rats in
      response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2
      is expressed only in response to nociceptive stimuli in the dorsal spinal horn,
      the current study demonstrates that non-noxious stimuli evoke allodynic response.
      Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2
      receptor (D2R) agonist, significantly decreased DMA compared to control rats
      injected with saline. These data demonstrate for the first time that
      nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at
      least involves a segmental mechanism. In addition, bromocriptine was shown to
      have a remarkable analgesic effect on this neuropathic pain symptom.

PMID- 24944867
TI  - Alterations in empathic responding among women with posttraumatic stress disorder
      associated with childhood trauma.
AB  - OBJECTIVE: Although studies increasingly point toward problems with social
      cognition among individuals with posttraumatic stress disorder (PTSD), few
      studies have assessed empathic responding. The aim of the current study was to
      investigate empathic responding in women with PTSD related to childhood trauma,
      and the contribution of parental bonding to empathic abilities in this sample.
      METHODS: Participants with PTSD (n = 29) and sex- and age-matched healthy
      controls (n = 20) completed two self-report empathy measures, the Interpersonal
      Reactivity Index (IRI) and the Toronto Empathy Questionnaire (TEQ), and a self
      report measure of attachment, the Parental Bonding Instrument (PBI). RESULTS:
      Women with PTSD, relative to controls, reported significantly lower levels of
      empathic concern (r = 0.29) and perspective taking (r = 0.30), yet significantly
      higher levels of personal distress (r = 0.45) on the IRI. Women with PTSD also
      reported elevated scores on the TEQ (eta (2) = 0.13). Levels of paternal care on
      the PBI, rather than childhood trauma severity or PTSD symptom severity best
      predicted perspective taking scores on the IRI in the PTSD sample (R (2) = 0.20).
      CONCLUSION: Women with PTSD associated with childhood trauma reported alterations
      among different domains of empathic functioning that may be related to low levels
      of paternal care.

PMID- 24944868
TI  - Noncontinuous use of antidepressant in adults with major depressive disorders - a
      retrospective cohort study.
AB  - BACKGROUND: Noncontinuous antidepressant use is frequently observed in clinical
      practice despite the standard recommendation of at least 6-9 months of continuous
      treatment. The problem may be more serious in Chinese populations where
      stigmatization is common. This retrospective cohort study investigated the rate
      of noncontinuous antidepressant use and subsequent rate of relapse and recurrence
      in psychiatric Chinese outpatients by examining the prescription records,
      electronic medical records, and written medical records. Factors associated with
      noncontinuous antidepressant use were also identified. METHODS: We reviewed the
      medical records of 189 patients newly dispensed with an antidepressant in the
      psychiatric outpatient clinic during year 2006 and 2007. Primary outcome was the
      rate of noncontinuous antidepressant use within 6 months of therapy. Secondary
      outcomes included the factors associated with noncontinuous antidepressant use
      and the rate of subsequent depression relapse and recurrence within 1 year of
      starting treatment. RESULTS: Among the 189 subjects included in this study, 46%
      were noncontinuous users of the newly prescribed antidepressant therapy. The
      noncontinuous users were found to have an eightfold increase (OR: 8.42, 95% CI:
      3.30-21.47) in the risks of relapse/recurrence depressive episodes within 1 year
      after treatment initiation. Younger age (P = 0.008), female, (P = 0.029),
      residency in public housing estate (P = 0.029), experiencing side effects (P =
      0.024), infrequent follow-ups (P = 0.006), and earlier onset of diagnosis (P =
      0.034) were factors significantly associated with noncontinuous antidepressant
      use. CONCLUSIONS: Noncontinuous antidepressant use is common in the local Chinese
      depressive patients and associated with a high rate of relapse and recurrence.
      Collaborative multidisciplinary approaches that target patient education and
      enhancement of follow-up adherence are needed.

PMID- 24944869
TI  - The left inferior frontal gyrus is involved in adjusting response bias during a
      perceptual decision-making task.
AB  - INTRODUCTION: Changing the way we make decisions from one environment to another
      allows us to maintain optimal decision-making. One way decision-making may change
      is how biased one is toward one option or another. Identifying the regions of the
      brain that underlie the change in bias will allow for a better understanding of
      flexible decision-making. METHODS: An event-related, perceptual decision-making
      task where participants had to detect a picture of an animal amongst distractors
      was used during functional magnetic resonance imaging. Positive and negative
      financial motivation were used to affect a change in response bias, and changes
      in decision-making behavior were quantified using signal detection theory.
      RESULTS: Response bias became relatively more liberal during both positive and
      negative motivated trials compared to neutral trials. For both motivational
      conditions, the larger the liberal shift in bias, the greater the left inferior
      frontal gyrus (IFG) activity. There was no relationship between individuals'
      belief that they used a different strategy and their actual change in response
      bias. CONCLUSIONS: The present findings suggest that the left IFG plays a role in
      adjusting response bias across different decision environments. This suggests a
      potential role for the left IFG in flexible decision-making.

PMID- 24944870
TI  - The development and expression of physical nicotine dependence corresponds to
      structural and functional alterations in the anterior cingulate-precuneus
      pathway.
AB  - INTRODUCTION: Perturbations in neural function provoked by a drug are thought to
      induce neural adaptations, which, in the absence of the drug, give rise to
      withdrawal symptoms. Previously published structural data from this study
      indicated that the progressive development of physical dependence is associated
      with increasing density of white matter tracts between the anterior cingulum
      bundle and the precuneus. METHODS: Using functional magnetic resonance imaging,
      we compared 11 smokers after 11 h of abstinence from nicotine and after
      satiation, with 10 nonsmoking controls, using independent component analysis for
      brain network comparisons as well as a whole brain resting-state functional
      connectivity analysis using the anterior cingulate cortex as a seed. RESULTS:
      Independent component analysis demonstrated increased functional connectivity in
      brain networks such as the default mode network associated with the withdrawal
      state in multiple brain regions. In seed-based analysis, smokers in the
      withdrawal state showed stronger functional connectivity than nonsmoking controls
      between the anterior cingulate cortex and the precuneus, caudate, putamen, and
      frontal cortex (P < 0.05). Among smokers, compared to the satiated state,
      nicotine withdrawal was associated with increased connectivity between the
      anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus,
      superior frontal gyrus, posterior cingulate cortex, superior temporal, and
      inferior temporal lobe (P < 0.02). The intensity of withdrawal-induced craving
      correlated with the strength of connectivity between the anterior cingulate
      cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and
      precentral gyrus (r = 0.60-0.76; P < 0.05). CONCLUSIONS: In concordance with our
      previous report that structural neural connectivity between the anterior
      cingulate area and the precuneus increased in proportion to the progression of
      physical dependence, resting-state functional connectivity in this pathway
      increases during nicotine withdrawal in correlation with the intensity of
      withdrawal-induced craving. These findings suggest that smoking triggers
      structural and functional neural adaptations in the brain that support withdrawal
      induced craving.

PMID- 24944871
TI  - Candidate gene associations with mood disorder, cognitive vulnerability, and
      fronto-limbic volumes.
AB  - BACKGROUND: Four of the most consistently replicated variants associated with
      mood disorder occur in genes important for synaptic function: ANK3 (rs10994336),
      BDNF (rs6265), CACNA1C (rs1006737), and DGKH (rs1170191). AIMS: The present study
      examined associations between these candidates, mood disorder diagnoses,
      cognition, and fronto-limbic regions implicated in affect regulation. METHODS AND
      MATERIALS: Participants included 128 individuals with bipolar disorder (33% male,
      Mean age = 38.5), 48 with major depressive disorder (29% male, Mean age = 40.4),
      and 149 healthy controls (35% male, Mean age = 36.5). Genotypes were determined
      by 5'-fluorogenic exonuclease assays (TaqMan(r)). Fronto-limbic volumes were
      obtained from high resolution brain images using Freesurfer. Chi-square analyses,
      bivariate correlations, and mediational models examined relationships between
      genetic variants, mood diagnoses, cognitive measures, and brain volumes. RESULTS:
      Carriers of the minor BDNF and ANK3 alleles showed nonsignificant trends toward
      protective association in controls relative to mood disorder patients (P =
      0.047). CACNA1C minor allele carriers had larger bilateral caudate, insula,
      globus pallidus, frontal pole, and nucleus accumbens volumes (smallest r = 0.13,
      P = 0.043), and increased IQ (r = 0.18, P < 0.001). CACNA1C associations with
      brain volumes and IQ were independent; larger fronto-limbic volumes did not
      mediate increased IQ. Other candidate variants were not significantly associated
      with diagnoses, cognition, or fronto-limbic volumes. DISCUSSION AND CONCLUSIONS:
      CACNA1C may be associated with biological systems altered in mood disorder.
      Increases in fronto-limbic volumes and cognitive ability associated with CACNA1C
      minor allele genotypes are congruent with findings in healthy samples and may be
      a marker for increased risk for neuropsychiatric phenotypes. Even larger
      multimodal studies are needed to quantify the magnitude and specificity of
      genetic-imaging-cognition-symptom relationships.

PMID- 24944872
TI  - Muscarinic acetylcholine receptors are expressed by most parvalbumin
      immunoreactive neurons in area MT of the macaque.
AB  - BACKGROUND: In the mammalian neocortex, cells that express parvalbumin (PV
      neurons) comprise a dominant class of inhibitory neuron that substantially
      overlaps with the fast/narrow-spiking physiological phenotype. Attention has
      pronounced effects on narrow-spiking neurons in the extrastriate cortex of
      macaques, and more consistently so than on their broad-spiking neighbors.
      Cortical neuromodulation by acetylcholine (ACh) is a candidate mechanism for
      aspects of attention and in the primary visual cortex (V1) of the macaque,
      receptors for ACh (AChRs) are strongly expressed by inhibitory neurons. In
      particular, most PV neurons in macaque V1 express m1 muscarinic AChRs and
      exogenously applied ACh can cause the release of gamma-aminobutyric acid. In
      contrast, few PV neurons in rat V1 express m1 AChRs. While this could be a
      species difference, it has also been argued that macaque V1 is anatomically
      unique when compared with other cortical areas in macaques. AIMS: The aim of this
      study was to better understand the extent to which V1 offers a suitable model
      circuit for cholinergic anatomy in the macaque occipital lobe, and to explore
      cholinergic modulation as a biological basis for the changes in circuit behavior
      seen with attention. MATERIALS AND METHODS: We compared expression of m1 AChRs by
      PV neurons between area V1 and the middle temporal visual area (MT) in macaque
      monkeys using dual-immunofluorescence confocal microscopy. RESULTS AND
      CONCLUSION: We find that, as in V1, most PV neurons in MT express m1 AChRs but,
      unlike in V1, it appears that so do most excitatory neurons. This provides
      support for V1 as a model of cholinergic modulation of inhibition in macaque
      visual cortex, but not of cholinergic modulation of visual cortical circuits in
      general. We also propose that ACh acting via m1 AChRs is a candidate underlying
      mechanism for the strong effects of attention on narrow-spiking neurons observed
      in behaving animals.

PMID- 24944873
TI  - Morbidity in early Parkinson's disease and prior to diagnosis.
AB  - BACKGROUND: Nonmotor symptoms are probably present prior to, early on, and
      following, a diagnosis of Parkinson's disease. Nonmotor symptoms may hold
      important information about the progression of Parkinson's disease. OBJECTIVE: To
      evaluated the total early and prediagnostic morbidities in the 3 years before a
      hospital contact leading to a diagnosis of Parkinson's disease. METHODS:
      Retrospective morbidity data from Danish National Patient Registry records (1997
      2007) of 10,490 adult patients with a secondary care diagnosis of Parkinson's
      disease were compared with 42,505 control cases. RESULTS: Parkinson's disease was
      associated with significantly higher morbidity rates associated with conditions
      in the following categories: mental and psychiatric, nervous system,
      gastrointestinal, musculoskeletal system and connective tissue, genitourinary,
      abnormal clinical and laboratory findings, injury, poisoning and certain other
      external causes, and other factors influencing health status and contact with
      health services. It was negatively associated with neoplasm, cardiovascular, and
      respiratory diseases. CONCLUSIONS: Patients with a diagnosis of Parkinson's
      disease present significant differences in morbidities early on, following, and
      prior to, their diagnosis, compared with healthy controls.

PMID- 24944876
TI  - Secular trend of sex ratio and symptom patterns among children with autism
      spectrum disorders.
AB  - An information technology invention embodied in a website serving the interests
      of the autism community was designed to "let the data talk." By its use, the
      authors have detected a downward temporal trend in 2013 in the sex ratio of 2431
      members of Autism360.org from a yearly average between 2010 and 2012 of 4.24 to
      3.01 in 2013. As of the first two months of 2014, the average sex ratio is 2.69.
      We report contemporaneous changes in previously reported male vs female symptom
      patterns. Such changes suggest a convergence in which distinctive severity of
      certain grouped central nervous, emotional, and immune profile items in females
      have diminished toward that of males. The data also show correlations among these
      profile items that add further credence to the sex ratio findings. A wider
      dispersion of the female data as compared with the male data was found in the
      year preceding the downward trend in the mean sex ratio. The authors suggest that
      such a trend toward an increase in the variance of the data points to instability
      in the biological system-the autism spectrum. We conclude that public policy
      would be better served by monitoring changes in the standard deviation as
      compared with the mean in large data sets to better anticipate changes. The
      findings we report raise questions based on known sex differences in
      detoxification chemistry. One such question would be whether maternal, fetal, or
      individual exposure to a novel environmental factor may have breached the taller
      fence of female protection from toxins. 

PMID- 24944875
TI  - Salutogenesis: the defining concept for a new healthcare system.

PMID- 24944877
TI  - Peace village international: ongoing patient reports?

PMID- 24944878
TI  - The Ecology of Sustainable Implementation: Reflection on a 10-Year Case History
      Illustration.
AB  - The primary aim of this paper is to illustrate the strategic and ecological
      nature of implementation. The ultimate aim of implementation is not dissemination
      but sustainability beyond the implementation effort. A case study is utilized to
      illustrate these broad and long-term perspectives of sustainable implementation
      based on qualitative analyses of a 10-year implementation effort. The purveyors
      aimed to develop selective community prevention services for children in families
      burdened by parental psychiatric or addictive problems. Services were gradually
      disseminated to 23 sites serving 40 municipalities by 2013. Up to 2013, only one
      site terminated services after initial implementation. Although many sites
      suspended services for shorter periods, services are still offered at 22 sites.
      This case analysis is based on project reports, user evaluations, practitioner
      interviews, and service statistics. The paper focuses on the analyses and
      strategies utilized to cope with quality decay and setbacks as well as progress
      and success in disseminating and sustaining the services and their quality. Low
      cost multilevel strategies to implement services at the community level were
      organized by a prevention unit in child psychiatry, supervised by a university
      department (purveyors). The purveyors were also involved in national and
      international collaboration and development. Multilevel strategies included
      manualized intervention, in-practice training methods, organizational
      responsibility, media strategies, service evaluation, staff motivation
      maintenance, quality assurance, and proposals for new law regulations. These case
      history aspects will be discussed in relation to the implementation literature,
      focusing on possible applicability across settings.

PMID- 24944879
TI  - Assessment of nitrate-N contamination in the Chunnakam aquifer system, Jaffna
      Peninsula, Sri Lanka.
AB  - Jaffna peninsula in Sri Lanka is an area of intensive agriculture using extensive
      organic and inorganic nitrogenous compounds and hence, this study was focused on
      assessing vulnerability of karstic aquifer system with specific focus on nitrate
      contamination, and compare loads of nitrate from agriculture. The total number of
      the wells sampled in the Chunnakam aquifer is 44. The coverage of wells with
      measurements of nitrate and nitrite concentrations in the database covering the
      study period from Januray, 2011 to August, 2011. The intrinsic vulnerability of
      the area is estimated by the DRASTIC model and the modified DRASTIC method was
      used to determine the nitrate-specific vulnerability of the aquifers. Average
      concentrations of nitrate-N and nitrite-N during the study period were 4.869 and
      0.014 mg/L respectively. The average number of wells exceeding permissible level
      of NO3-N is approximately 6-12, which means that about 14-28% out of the 44
      wells. Modified DRASTIC (DI) index value computed as explained above increased
      from DI = 177 to a range of 182 to 197. In spite of the increase, the Modified DI
      values show that the aquifer vulnerability specific to nitrate contamination
      remains in "high" category. Although nitrogen loading at the domestic sources and
      irrigation is of the same order of magnitude, the loading from fertilizer input
      is much larger which is about 15 times higher. This finding suggests that the
      fertilizer input in agricultural areas constitute a significant contribution to
      the nitrogen content in the groundwater and soils in agricultural areas of
      Jaffna. 

PMID- 24944880
TI  - Surface plasmon resonance properties of silver nanoparticle 2D sheets on metal
      gratings.
AB  - Grating-coupled propagating surface plasmons associated with silver-nanoparticle
      2D crystalline sheets exhibit sensitive plasmonic resonance tuning. Multilayered
      silver-nanoparticle 2D crystalline sheets are fabricated on gold or silver
      grating surfaces by the Langmuir- Blodgett method. We show that the deposition of
      Ag crystalline nanosheets on Au or Ag grating surfaces causes a drastic change in
      propagating surface plasmon resonance (SPR) both in angle measurements at fixed
      wavelengths and in fixed incident-angle mode by irradiation of white light. The
      dielectric constant of the multilayered silver nanosheet is estimated by a
      rigorous coupled-wave analysis. We find that the dielectric constant drastically
      increases as the number of silver-nanosheet layers increases. The experimentally
      obtained SP dispersions of Ag crystalline nanosheets on Au and Ag gratings are
      compared with the calculated SP dispersion curves. The drastic change in the
      surface plasmon resonance caused by the deposition of Ag-nanoparticle 2D
      crystalline sheets on metal grating surfaces suggests the potential for
      applications in highly sensitive sensors or for plasmonic devices requiring
      greatly enhanced electric fields. 

PMID- 24944881
TI  - Identification of causative pregnancy of gestational trophoblastic neoplasia
      diagnosed during pregnancy by short tandem repeat analysis.
AB  - *Gestational trophoblastic neoplasia can arise during the first trimester
      originating from trophoblasts of concurrent pregnancy.*Intraplacental
      choriocarcinoma can be developed from trophoblasts of a previous pregnancy. 

PMID- 24944882
TI  - Lupus nephritis associated with placental site trophoblastic tumor: A case report
      and review of the literature.
AB  - *An improved YASSO model is proposed by considering residual spatial
      autocorrelation.*Model prediction errors are minimised using GIS data at the
      appropriate spatial scale.*Topographical factors describe 24-49% of variation in
      soil carbon. 

PMID- 24944884
TI  - Molecular mechanisms in the selective basal activation of pyrabactin receptor 1:
      Comparative analysis of mutants.
AB  - Pyrabactin receptors (PYR) play a central role in abscisic acid (ABA) signal
      transduction; they are ABA receptors that inhibit type 2C protein phosphatases
      (PP2C). Molecular aspects contributing to increased basal activity of PYR against
      PP2C are studied by molecular dynamics (MD) simulations. An extensive series of
      MD simulations of the apo-form of mutagenized PYR1 as a homodimer and in complex
      with homology to ABA-insensitive 1 (HAB1) phosphatase are reported. In order to
      investigate the detailed molecular mechanisms mediating PYR1 activity, the MD
      data was analyzed by essential collective dynamics (ECD), a novel approach that
      allows the identification, with atomic resolution, of persistent dynamic
      correlations based on relatively short MD trajectories. Employing the ECD method,
      the effects of select mutations on the structure and dynamics of the PYR1
      complexes were investigated and considered in the context of experimentally
      determined constitutive activities against HAB1. Approaches to rationally design
      constitutively active PYR1 constructs to increase PP2C inhibition are discussed. 

PMID- 24944883
TI  - Tumor suppressive miRNA-34a suppresses cell proliferation and tumor growth of
      glioma stem cells by targeting Akt and Wnt signaling pathways.
AB  - MiRNA-34a is considered as a potential prognostic marker for glioma, as studies
      suggest that its expression negatively correlates with patient survival in grade
      III and IV glial tumors. Here, we show that expression of miR-34a was decreased
      in a graded manner in glioma and glioma stem cell-lines as compared to normal
      brain tissues. Ectopic expression of miR-34a in glioma stem cell-lines HNGC-2 and
      NSG-K16 decreased the proliferative and migratory potential of these cells,
      induced cell cycle arrest and caused apoptosis. Notably, the miR-34a glioma cells
      formed significantly smaller xenografts in immuno-deficient mice as compared with
      control glioma stem cell-lines. Here, using a bioinformatics approach and various
      biological assays, we identify Rictor, as a novel target for miR-34a in glioma
      stem cells. Rictor, a defining component of mTORC2 complex, is involved in cell
      survival signaling. mTORC2 lays downstream of Akt, and thus is a direct activator
      of Akt. Our earlier studies have elaborated on role of Rictor in glioma invasion
      (Das et al., 2011). Here, we demonstrate that miR34a over-expression in glioma
      stem cells profoundly decreased levels of p-AKT (Ser473), increased GSK-3beta
      levels and targeted for degradation beta-catenin, an important mediator of Wnt
      signaling pathway. This led to diminished levels of the Wnt effectors cyclin D1
      and c-myc. Collectively, we show that the tumor suppressive function of miR-34a
      in glioblastoma is mediated via Rictor, which through its effects on AKT/mTOR
      pathway and Wnt signaling causes pronounced effects on glioma malignancy. 

PMID- 24944886
TI  - Letter-to-the-editor on "Not so hot: Optimal housing temperatures for mice to
      mimic the thermal environment of humans".

PMID- 24944887
TI  - Not so nuanced: Reply to the comments of Gaskill and Garner on 'Not so hot:
      Optimal housing temperatures for mice to mimic the environment of humans'.

PMID- 24944885
TI  - Unmasking cryptococcal meningitis immune reconstitution inflammatory syndrome in
      pregnancy induced by HIV antiretroviral therapy with postpartum paradoxical
      exacerbation.
AB  - Cryptococcosis is the most common cause of meningitis in Africa due to the high
      burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent
      and deadly complication of cryptococcal meningitis. We report a fatal case of
      cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral
      therapy (unmasking IRIS) and markedly worsened postpartum after delivery
      (paradoxical IRIS). 

PMID- 24944888
TI  - A tale of two methods: Identifying neuronal CB1 receptors.

PMID- 24944889
TI  - Studying mitochondrial CB1 receptors: Yes we can.

PMID- 24944890
TI  - What does indirect calorimetry really tell us?

PMID- 24944891
TI  - Should we abandon indirect calorimetry as a tool to diagnose energy expenditure?
      Not yet. Perhaps not ever. Commentary on Burnett and Grobe (2014).

PMID- 24944892
TI  - A mighty (ochondrial) fight?

PMID- 24944893
TI  - Fabp4, a new player in the adipo-pancreatic axis.

PMID- 24944894
TI  - mTORC2, the "other" mTOR, is a new player in energy balance regulation.

PMID- 24944895
TI  - Do mitochondria care about insulin resistance?

PMID- 24944897
TI  - Circadian control of glucose metabolism.
AB  - The incidence of obesity and type 2 diabetes mellitus (T2DM) has risen to
      epidemic proportions. The pathophysiology of T2DM is complex and involves insulin
      resistance, pancreatic beta-cell dysfunction and visceral adiposity. It has been
      known for decades that a disruption of biological rhythms (which happens the most
      profoundly with shift work) increases the risk of developing obesity and T2DM.
      Recent evidence from basal studies has further sparked interest in the
      involvement of daily rhythms (and their disruption) in the development of obesity
      and T2DM. Most living organisms have molecular clocks in almost every tissue,
      which govern rhythmicity in many domains of physiology, such as rest/activity
      rhythms, feeding/fasting rhythms, and hormonal secretion. Here we present the
      latest research describing the specific role played by the molecular clock
      mechanism in the control of glucose metabolism and speculate on how disruption of
      these tissue clocks may lead to the disturbances in glucose homeostasis. 

PMID- 24944898
TI  - Osteopontin: A novel regulator at the cross roads of inflammation, obesity and
      diabetes.
AB  - Since its first description more than 20 years ago osteopontin has emerged as an
      active player in many physiological and pathological processes, including
      biomineralization, tissue remodeling and inflammation. As an extracellular matrix
      protein and proinflammatory cytokine osteopontin is thought to facilitate the
      recruitment of monocytes/macrophages and to mediate cytokine secretion in
      leukocytes. Modulation of immune cell response by osteopontin has been associated
      with various inflammatory diseases and may play a pivotal role in the development
      of adipose tissue inflammation and insulin resistance. Here we summarize recent
      findings on the role of osteopontin in metabolic disorders, particularly focusing
      on diabetes and obesity. 

PMID- 24944896
TI  - Integrated physiology and systems biology of PPARalpha.
AB  - The Peroxisome Proliferator Activated Receptor alpha (PPARalpha) is a
      transcription factor that plays a major role in metabolic regulation. This review
      addresses the functional role of PPARalpha in intermediary metabolism and
      provides a detailed overview of metabolic genes targeted by PPARalpha, with a
      focus on liver. A distinction is made between the impact of PPARalpha on
      metabolism upon physiological, pharmacological, and nutritional activation. Low
      and high throughput gene expression analyses have allowed the creation of a
      comprehensive map illustrating the role of PPARalpha as master regulator of lipid
      metabolism via regulation of numerous genes. The map puts PPARalpha at the center
      of a regulatory hub impacting fatty acid uptake, fatty acid activation,
      intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid
      oxidation, ketogenesis, triglyceride turnover, lipid droplet biology,
      gluconeogenesis, and bile synthesis/secretion. In addition, PPARalpha governs the
      expression of several secreted proteins that exert local and endocrine functions.

PMID- 24944900
TI  - Mitochondrial dysfunction has divergent, cell type-dependent effects on insulin
      action.
AB  - The contribution of mitochondrial dysfunction to insulin resistance is a
      contentious issue in metabolic research. Recent evidence implicates mitochondrial
      dysfunction as contributing to multiple forms of insulin resistance. However,
      some models of mitochondrial dysfunction fail to induce insulin resistance,
      suggesting greater complexity describes mitochondrial regulation of insulin
      action. We report that mitochondrial dysfunction is not necessary for cellular
      models of insulin resistance. However, impairment of mitochondrial function is
      sufficient for insulin resistance in a cell type-dependent manner, with impaired
      mitochondrial function inducing insulin resistance in adipocytes, but having no
      effect, or insulin sensitising effects in hepatocytes. The mechanism of
      mitochondrial impairment was important in determining the impact on insulin
      action, but was independent of mitochondrial ROS production. These data can
      account for opposing findings on this issue and highlight the complexity of
      mitochondrial regulation of cell type-specific insulin action, which is not
      described by current reductionist paradigms. 

PMID- 24944899
TI  - Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.
AB  - Insulin signaling in the central nervous system (CNS) regulates energy balance
      and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit
      of the mTORC2 complex and is required for hydrophobic motif site phosphorylation
      of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2
      signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre
      LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC
      or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat
      mass and adiposity, glucose intolerance and behavioral leptin resistance.
      Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting
      hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion
      did not impact energy balance but led to mild glucose intolerance. Collectively,
      we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is
      important for central regulation of energy and glucose homeostasis. 

PMID- 24944901
TI  - Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat
      and alters global protein acetylation.
AB  - Lipid deposition in the liver is associated with metabolic disorders including
      fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes
      acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat
      storage; therefore, their inhibition is expected to prevent the development of
      fatty liver. In this study we generated liver-specific ACC1 and ACC2 double
      knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat
      metabolism and whole-body physiology. Characterization of LDKO mice revealed
      unexpected phenotypes of increased hepatic triglyceride and decreased fat
      oxidation. We also observed that chronic ACC inhibition led to hyper-acetylation
      of proteins in the extra-mitochondrial space. In sum, these data reveal the
      existence of a compensatory pathway that protects hepatic fat stores when ACC
      enzymes are inhibited. Furthermore, we identified an important role for ACC
      enzymes in the regulation of protein acetylation in the extra-mitochondrial
      space. 

PMID- 24944902
TI  - Effects of chronic leptin infusion on subsequent body weight and composition in
      mice: Can body weight set point be reset?
AB  - Circulating leptin concentrations correlate with fat mass and signal the status
      of somatic energy stores to the brain. Previous studies suggest that diet-induced
      elevations of body weight increase body weight "set-point". To assess whether
      chronic hyperleptinemia is responsible for this shift in defended body weight, we
      elevated circulating leptin concentrations in lean mice to those comparable to
      diet-induced obese mice for eighteen weeks. We hypothesized that following
      cessation of leptin infusion, a higher body weight would be defended. Compared to
      saline-infused controls, leptin-infused mice had elevated circulating leptin
      concentrations, gained less weight, yet had similar metabolic rates. Following
      cessation of leptin administration, leptin-infused mice gained some weight yet
      plateaued at 5-10% below controls. These results suggest that, unlike mice
      rendered hyperleptinemic by diet-induced weight gain, leptin-infused mice do not
      subsequently "defend" a higher body weight, suggesting that hyperleptinemia per
      se does not mimic the CNS consequences of chronic weight gain. 

PMID- 24944903
TI  - Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP.
AB  - Kruppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed
      in a range of tissues that plays multiple functions. We report that hypothalamic
      KLF4 represents a new transcription factor specifically modulating agouti-related
      protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP
      neurons and is modulated by nutritional status and leptin. Over-expression of
      KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases
      body weight through the specific stimulation of AgRP, as well as blunting leptin
      sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down
      regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean
      and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own,
      enhance peripheral leptin sensitivity in DIO rats. 

PMID- 24944904
TI  - Glut4 expression defines an insulin-sensitive hypothalamic neuronal population.
AB  - Insulin signaling in the CNS modulates satiety and glucose metabolism, but
      insulin target neurons are poorly defined. We have previously shown that ablation
      of insulin receptors (InsR) in Glut4-expressing tissues results in systemic
      abnormalities of insulin action. We propose that Glut4 neurons constitute an
      insulin-sensitive neuronal subset. We determined their gene expression profiles
      using flow-sorted hypothalamic Glut4 neurons. Gene ontology analyses demonstrated
      that Glut4 neurons are enriched in olfacto-sensory receptors, M2 acetylcholine
      receptors, and pathways required for the acquisition of insulin sensitivity.
      Following genetic ablation of InsR, transcriptome profiling of Glut4 neurons
      demonstrated impairment of the insulin, peptide hormone, and cAMP signaling
      pathways, with a striking upregulation of anion homeostasis pathway. Accordingly,
      hypothalamic InsR-deficient Glut4 neurons showed reduced firing activity. The
      molecular signature of Glut4 neurons is consistent with a role for this neural
      population in the integration of olfacto-sensory cues with hormone signaling to
      regulate peripheral metabolism. 

PMID- 24944905
TI  - Dietary effects on resting metabolic rate in C57BL/6 mice are differentially
      detected by indirect (O2/CO2 respirometry) and direct calorimetry.
AB  - Resting metabolic rate (RMR) studies frequently involve genetically-manipulated
      mice and high fat diets (HFD). We hypothesize that the use of inadequate methods
      impedes the identification of novel regulators of RMR. This idea was tested by
      simultaneously measuring RMR by direct calorimetry and respirometry in C57BL/6J
      mice fed chow, 45% HFD, and then returned to chow. Comparing results during chow
      feeding uncovered an underestimation of RMR by respirometry (0.010 +/- 0.001
      kcal/h, P < 0.05), which is equivalent in magnitude to ~2% of total daily caloric
      turnover. RMR during 45% HFD feeding was increased by respirometry (+0.013 +/-
      0.003 kcal/h, P < 0.05), but not direct calorimetry (+0.001 +/- 0.002 kcal/h).
      Both methods indicated that return to chow reduced RMR compared to HFD, though
      direct calorimetry indicated a reduction below the initial chow fed state (-0.019
      +/- 0.004 kcal/h versus baseline, P < 0.05) that was not detected by respirometry
      (-0.003 +/- 0.002 kcal/h versus baseline). These results highlight method
      specific interpretations of the effects of dietary interventions upon RMR in
      mice, and prompt the reevaluation of preclinical screening methods used to
      identify novel RMR modulators. 

PMID- 24944906
TI  - Identification of fatty acid binding protein 4 as an adipokine that regulates
      insulin secretion during obesity.
AB  - A critical feature of obesity is enhanced insulin secretion from pancreatic beta
      cells, enabling the majority of individuals to maintain glycaemic control despite
      adiposity and insulin resistance. Surprisingly, the factors coordinating this
      adaptive beta-cell response with adiposity have not been delineated. Here we show
      that fatty acid binding protein 4 (FABP4/aP2) is an adipokine released from
      adipocytes under obesogenic conditions, such as hypoxia, to augment insulin
      secretion. The insulinotropic action of FABP4 was identified using an in vitro
      system that recapitulates adipocyte to beta-cell endocrine signalling, with
      glucose-stimulated insulin secretion (GSIS) as a functional readout, coupled with
      quantitative proteomics. Exogenous FABP4 potentiated GSIS in vitro and in vivo,
      and circulating FABP4 levels correlated with GSIS in humans. Insulin inhibited
      FABP4 release from adipocytes in vitro, in mice and in humans, consistent with
      feedback regulation. These data suggest that FABP4 and insulin form an endocrine
      loop coordinating the beta-cell response to obesity. 

PMID- 24944907
TI  - Brown adipose tissue derived VEGF-A modulates cold tolerance and energy
      expenditure.
AB  - We recently reported that local overexpression of VEGF-A in white adipose tissue
      (WAT) protects against diet-induced obesity and metabolic dysfunction. The
      observation that VEGF-A induces a "brown adipose tissue (BAT)-like" phenotype in
      WAT prompted us to further explore the direct function of VEGF-A in BAT. We
      utilized a doxycycline (Dox)-inducible, brown adipocyte-specific VEGF-A
      transgenic overexpression model to assess direct effects of VEGF-A in BAT in
      vivo. We observed that BAT-specific VEGF-A expression increases vascularization
      and up-regulates expression of both UCP1 and PGC-1alpha in BAT. As a result, the
      transgenic mice show increased thermogenesis during chronic cold exposure. In
      diet-induced obese mice, introducing VEGF-A locally in BAT rescues capillary
      rarefaction, ameliorates brown adipocyte dysfunction, and improves deleterious
      effects on glucose and lipid metabolism caused by a high-fat diet challenge.
      These results demonstrate a direct positive role of VEGF-A in the activation and
      expansion of BAT. 

PMID- 24944908
TI  - Metabolic memory of beta-cells controls insulin secretion and is mediated by
      CaMKII.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) functions both in
      regulation of insulin secretion and neurotransmitter release through common
      downstream mediators. Therefore, we hypothesized that pancreatic beta-cells
      acquire and store the information contained in calcium pulses as a form of
      "metabolic memory", just as neurons store cognitive information. To test this
      hypothesis, we developed a novel paradigm of pulsed exposure of beta-cells to
      intervals of high glucose, followed by a 24-h consolidation period to eliminate
      any acute metabolic effects. Strikingly, beta-cells exposed to this high-glucose
      pulse paradigm exhibited significantly stronger insulin secretion. This metabolic
      memory was entirely dependent on CaMKII. Metabolic memory was reflected on the
      protein level by increased expression of proteins involved in glucose sensing and
      Ca(2+)-dependent vesicle secretion, and by elevated levels of the key beta-cell
      transcription factor MAFA. In summary, like neurons, human and mouse beta-cells
      are able to acquire and retrieve information. 

PMID- 24944909
TI  - A standardized infrared imaging technique that specifically detects UCP1-mediated
      thermogenesis in vivo.
AB  - The activation and expansion of brown adipose tissue (BAT) has emerged as a
      promising strategy to counter obesity and the metabolic syndrome by increasing
      energy expenditure. The subsequent testing and validation of novel agents that
      augment BAT necessitates accurate pre-clinical measurements in rodents regarding
      the capacity for BAT-derived thermogenesis. We present a novel method to measure
      BAT thermogenesis using infrared imaging following beta3-adrenoreceptor
      stimulation in mice. We show that the increased body surface temperature observed
      using this method is due solely to uncoupling protein-1 (UCP1)-mediated
      thermogenesis and that this technique is able to discern differences in BAT
      activity in mice acclimated to 23  degrees C or thermoneutrality (30  degrees C).
      These findings represent the first standardized method utilizing infrared imaging
      to specifically detect UCP1 activity in vivo. 

PMID- 24944910
TI  - Cannabinoid control of brain bioenergetics: Exploring the subcellular
      localization of the CB1 receptor.
AB  - Brain mitochondrial activity is centrally involved in the central control of
      energy balance. When studying mitochondrial functions in the brain, however,
      discrepant results might be obtained, depending on the experimental approaches.
      For instance, immunostaining experiments and biochemical isolation of organelles
      expose investigators to risks of false positive and/or false negative results. As
      an example, the functional presence of cannabinoid type 1 (CB1) receptors on
      brain mitochondrial membranes (mtCB1) was recently reported and rapidly
      challenged, claiming that the original observation was likely due to artifact
      results. Here, we addressed this issue by directly comparing the procedures used
      in the two studies. Our results show that the use of appropriate controls and
      quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and
      that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists
      reliably decrease respiration in brain mitochondria. These data further underline
      the importance of adapted experimental procedures to study brain mitochondrial
      functions. 

PMID- 24944911
TI  - Establishing visit priorities for complex patients: A summary of the literature
      and conceptual model to guide innovative interventions.
AB  - With the aging of the population and continuing advances in health care, patients
      seen in the primary care setting are increasingly complex. At the same time, the
      number of screening and chronic condition management tasks primary care providers
      are expected to cover during brief primary care office visits has continued to
      grow. These converging trends mean that there is often not enough time during
      each visit to address all of the patient's concerns and needs, a significant
      barrier to effectively providing patient-centered care. For complex patients,
      prioritization of which issues to address during a given visit must precede
      discrete decisions about disease-specific treatment preferences and goals.
      Negotiating this process of setting priorities represents a major challenge for
      patient-centered primary care, as patient and provider priorities may not always
      be aligned. In this review, we present a synthesis of recent research on how
      patients and providers negotiate the visit process and describe a conceptual
      model to guide innovative approaches to more effective primary care visits for
      complex patients based on defining visit priorities. The goal of this model is to
      inform interventions that maximize the value of available time during the primary
      care encounter by facilitating communication between a prepared patient who has
      had time before the visit to identify his/her priorities and an informed provider
      who is aware of the patient's care priorities at the beginning of the visit. We
      conclude with a discussion of key questions that should guide future research and
      intervention development in this area.

PMID- 24944912
TI  - Zebrafish heart development is regulated via glutaredoxin 2 dependent migration
      and survival of neural crest cells.
AB  - Glutaredoxin 2 is a vertebrate specific oxidoreductase of the thioredoxin family
      of proteins modulating the intracellular thiol pool. Thereby, glutaredoxin 2 is
      important for specific redox signaling and regulates embryonic development of
      brain and vasculature via reversible oxidative posttranslational thiol
      modifications. Here, we describe that glutaredoxin 2 is also required for
      successful heart formation. Knock-down of glutaredoxin 2 in zebrafish embryos
      inhibits the invasion of cardiac neural crest cells into the primary heart field.
      This leads to impaired heart looping and subsequent obstructed blood flow.
      Glutaredoxin 2 specificity of the observed phenotype was confirmed by rescue
      experiments. Active site variants of glutaredoxin 2 revealed that the (de)
      glutathionylation activity is required for proper heart formation. Our data
      suggest that actin might be one target during glutaredoxin 2 regulated cardiac
      neural crest cell migration and embryonic heart development. In summary, this
      work represents further evidence for the general importance of redox signaling in
      embryonic development and highlights additionally the importance of glutaredoxin
      2 during embryogenesis. 

PMID- 24944914
TI  - Diabetes in Africa - Puzzles and challenges.

PMID- 24944915
TI  - Prevention of diabetes: How far have we gone?

PMID- 24944916
TI  - A revisit to prevailing care and challenges of managing diabetes in India: Focus
      on regional disparities.
AB  - An unprecedented rise in diabetes mellitus (DM) prevalence in India is the
      outcome of lifestyle changes in the background of genetic predisposition.
      Moreover, there are substantial regional variations in diabetes prevalence and
      management. The highest prevalence of DM was observed in southern region
      (Ernakulum, Kerala) and lowest prevalence was observed in North Eastern region
      (Manipur). Similarly large variations have been evident in overall awareness and
      diabetes care across the geographies within India. The regional challenges are
      largely affected by poor disease awareness, socioeconomic disparity and
      underutilization of the public health-care services. Though government has taken
      initiatives to address this issue, overall situation demands a collaborative
      effort from patients, health care professionals and the state. An exhaustive
      literature search was performed for articles and studies published on electronic
      databases. Present article assesses the regional disparity of diabetes
      epidemiology, current management practices and government policies for T2DM in
      India, identifies policy and research gaps, and suggests corrective measures to
      address the lacunae in diabetes care. 

PMID- 24944917
TI  - Consensus statement on diabetes in children.
AB  - While T1DM has been traditionally seen as a minor concern in the larger picture
      of pediatric ailments, new data reveals that the incidence of T1DM has assumed
      alarming proportions. It has long been clear that while the disease may be
      diagnosed at an early age, its impact is not isolated to afflicted children. The
      direct impact of the disease on the patient is debilitating due to the nature of
      the disease and lack of proper access to treatment in India. But this impact is
      further compounded by the utter apathy and often times antipathy, which patients
      withT1DM have to face. Lack of awareness of the issue in all stakeholders, low
      access to quality healthcare, patient, physician, and system level barriers to
      the delivery of optimal diabetes care are some of the factors which hinder
      successful management of T1DM. The first international consensus meet on diabetes
      in children was convened with the aim of providing a common platform to all the
      stakeholders in the management of T1DM, to discuss the academic, administrative
      and healthcare system related issues. The ultimate aim was to articulate the
      problems faced by children with diabetes in a way that centralized their position
      and focused on creating modalities of management sensitive to their needs and
      aspirations. It was conceptualized to raise a strong voice of advocacy for
      improving the management of T1DM and ensuring that "No child should die of
      diabetes". The unique clinical presentations of T1DM coupled with ignorance on
      the part of the medical community and society in general results in outcomes that
      are far worse than that seen with T2DM. So there is a need to substantially
      improve training of HCPs at all levels on this neglected aspect of healthcare. 

PMID- 24944913
TI  - Mitochondrial reactive oxygen species: a double edged sword in
      ischemia/reperfusion vs preconditioning.
AB  - Reductions in the blood supply produce considerable injury if the duration of
      ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs
      can exacerbate tissue damage and extend the size of an evolving infarct. Being
      highly metabolic organs, the heart and brain are particularly vulnerable to the
      deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic
      mechanisms contributing to I/R-induced tissue injury and infarction are
      multifactorial, the relative importance of each contributing factor remains
      unclear. However, an emerging body of evidence indicates that the generation of
      reactive oxygen species (ROS) by mitochondria plays a critical role in damaging
      cellular components and initiating cell death. In this review, we summarize our
      current understanding of the mechanisms whereby mitochondrial ROS generation
      occurs in I/R and contributes to myocardial infarction and stroke. In addition,
      mitochondrial ROS have been shown to participate in preconditioning by several
      pharmacologic agents that target potassium channels (e.g., ATP-sensitive
      potassium (mKATP) channels or large conductance, calcium-activated potassium
      (mBKCa) channels) to activate cell survival programs that render tissues and
      organs more resistant to the deleterious effects of I/R. Finally, we review novel
      therapeutic approaches that selectively target mROS production to reduce
      postischemic tissue injury, which may prove efficacious in limiting myocardial
      dysfunction and infarction and abrogating neurocognitive deficits and neuronal
      cell death in stroke. 

PMID- 24944918
TI  - Continuous glucose monitoring system and new era of early diagnosis of diabetes
      in high risk groups.
AB  - Continuous glucose monitoring (CGM) systems are an emerging technology that
      allows frequent glucose measurements to monitor glucose trends in real time.
      Their use as a diagnostic tool is still developing and appears to be promising.
      Combining intermittent glucose self-monitoring (SGM) and CGM combines the
      benefits of both. Significant improvement in the treatment modalities that may
      prevent the progress of prediabetes to diabetes have been achieved recently and
      dictates screening of high risk patients for early diagnosis and management of
      glycemic abnormalities. The use of CGMS in the diagnosis of early dysglycemia
      (prediabetes) especially in high risk patients appears to be an attractive
      approach. In this review we searched the literature to investigate the value of
      using CGMS as a diagnostic tool compared to other known tools, namely oral
      glucose tolerance test (OGTT) and measurement of glycated hemoglobin (HbA1C) in
      high risk groups. Those categories of patients include adolescents and adults
      with obesity especially those with family history of type 2 diabetes mellitus,
      polycystic ovary syndrome (PCO), gestational diabetes, cystic fibrosis,
      thalassemia major, acute coronary syndrome (ACS), and after renal
      transplantation. It appears that the ability of the CGMS for frequently
      monitoring (every 5 min) glucose changes during real-life settings for 3 to 5
      days stretches the chance to detect more glycemic abnormalities during basal and
      postprandial conditions compared to other short-timed methods. 

PMID- 24944919
TI  - Role of Glitazars in atherogenic dyslipidemia and diabetes: Two birds with one
      stone?
AB  - A triad of high triglycerides, low high-density lipoprotein (HDL) cholesterol,
      and elevated small dense low-density lipoprotein particles occurring in a patient
      with type 2 diabetes is referred to atherogenic diabetic dyslipidemia (ADD).
      Despite statin therapy, a significant residual risk remains potentially
      attributable to increased triglyceride concentration and low HDL cholesterol, a
      characteristic hallmark of ADD. Current therapeutic options in reducing this
      residual risk include nicotinic acid, omega 3 fatty acids, and selective
      peroxisome proliferator-activated receptor-alpha (PPAR) agonists (fibrates).
      These drugs are limited in their potential either by lack of evidence to support
      their role in reducing cardiovascular events or due to their side effects. This
      review details their current status and also the role of new glitazar,
      saroglitazar adual PPARalpha/gamma agonist with predominant PPARalpha activity in
      the management of ADD. 

PMID- 24944920
TI  - Endocrine dysfunction among adult patients with tuberculosis: An African
      experience.
AB  - A broad spectrum of endocrine conditions has been reported among adult patients
      with tuberculosis in Africa. This review aims to describe the magnitude and
      pathogenesis of the following endocrinopathies among patients with tuberculosis
      in Africa: adrenal insufficiency, diabetes mellitus, disorders of calcium and
      vitamin D metabolism, thyroid dysfunction and hypogonadism. PubMed database and
      Google scholar were used to search for the relevant published English language
      studies and case reports relating to endocrine abnormalities and tuberculosis in
      Africa up to July 2013. The search terms used were endocrine dysfunction,
      endocrine abnormalities, adrenal insufficiency, diabetes mellitus, thyroid
      dysfunction, hypogonadism, disorders of calcium and vitamin D metabolism,
      tuberculosis, Africa. Reference lists of the identified articles were further
      used to identify other studies. Adrenal insufficiency, diabetes mellitus and
      calcium-vitamin D abnormalities were the most prevalent and frequently reported
      endocrine disorders among adult patients with tuberculosis in Africa. A
      meticulous endocrine evaluation among tuberculosis patients with suspected
      endocrine abnormalities should be encouraged in Africa and other high TB endemic
      regions. Treatment of these endocrine disorders has generally been shown to
      improve quality of life and reduce mortality. 

PMID- 24944922
TI  - The endocrine quiz.
AB  - With the recent explosion in endocrine conferences, audience fatigue has set in
      and conference planners are now looking at newer pedagogic methods to revive the
      interest of audiences in these conferences. The endocrine quiz has finally come
      of vogue and is increasingly becoming one of the most popular attractions of any
      ranking endocrine conference. The endocrine quiz has a large and varied palette
      and draws questions from religious scriptures, history, literature, current
      affairs, sports, movies and basic and paramedical sciences. The more we delve
      into the quizzable aspects of endocrinology, the more we realize that
      endocrinology is ubiquitous and there is no sphere in human life untouched by
      endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction
      characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads
      of state like George Bush Sr and Boris Yeltsin, all have contributed to the
      melting pot of endocrine quizzing. Adding further grist to the endocrine mill are
      the Nobel prizes, with their attendant anecdotes and controversies. Step into
      this world of endocrine quizzing to have an up close and personal look at the
      diverse facets of this subject. 

PMID- 24944921
TI  - Imaging of vertebral fractures.
AB  - Vertebral fracture is a common clinical problem. Osteoporosis is the leading
      cause of non-traumatic vertebral fracture. Often, vertebral fractures are not
      clinically suspected due to nonspecific presentation and are overlooked during
      routine interpretation of radiologic investigations. Moreover, once detected,
      many a times the radiologist fails to convey to the clinician in a meaningful
      way. Hence, vertebral fractures are a constant cause of morbidity and mortality.
      Presence of vertebral fracture increases the chance of fracture in another
      vertebra and also increases the risk of subsequent hip fracture. Early detection
      can lead to immediate therapeutic intervention improving further the quality of
      life. So, in this review, we wish to present a comprehensive overview of
      vertebral fracture imaging along with an algorithm of evaluation of vertebral
      fractures. 

PMID- 24944923
TI  - Link between hypothyroidism and small intestinal bacterial overgrowth.
AB  - Altered gastrointestinal (GI) motility is seen in many pathological conditions.
      Reduced motility is one of the risk factors for development of a small intestinal
      bacterial overgrowth (SIBO). Hypothyroidism is associated with altered GI
      motility. The aim of this article was to study the link between hypothyroidism,
      altered GI motility and development of SIBO. Published literature was reviewed to
      study the association of altered GI motility, SIBO and hypothyroidism. Altered GI
      motility leads to SIBO. SIBO is common in patients with hypothyroidism. Patients
      with chronic GI symptoms in hypothyroidism should be evaluated for the
      possibility of SIBO. Both antibiotics and probiotics have been studied and found
      to be effective in management of SIBO. 

PMID- 24944924
TI  - Intravenous iron replacement therapy in eugonadal males with iron-deficiency
      anemia: Effects on pituitary gonadal axis and sperm parameters; A pilot study.
AB  - AIM OF THE STUDY: To evaluate semen parameters and to assess serum FSH, LH,
      Testosterone (T) concentrations before and 12 weeks after intravenous iron
      therapy (800-1200 mg elemental iron therapy - IVI) in adults with iron-deficiency
      anemia (IDA). MATERIALS AND METHODS: We studied 11 eugonadal adults with IDA,
      aged 40 +/- 5 years, due to defective intake of iron. Anemia was diagnosed when
      hemoglobin (Hb) was equal or below 10 g/dl. Serum iron, total iron-binding
      capacity (TIBC) and ferritin concentrations confirmed the diagnosis of IDA. Basal
      serum concentrations of FSH, LH, and T were measured. Semen parameters were
      evaluated before and 6-7 weeks after IVI therapy. RESULTS: After IVI therapy and
      correction of anemia, a significant increase of Hb from 8.1 +/- 1.17 g/dL to 13.1
      +/- 0.7 g/dL was observed and was associated with an increase of T (from 12.22 +/
      1.4 nmol/L to 15.9 +/- 0.96 nmol/L; P < 0.001), FSH (from 2.82 +/- 0.87 to 3.82
      +/- 1.08 IU/L; P = 0.007), and LH (from 2.27 +/- 0.9 to 3.82 +/- 1.5 IU/L; P =
      0.0002). Total sperm count (TSC) increased significantly from 72 +/- 17.5
      million/ml to 158 +/- 49 million/mL (P < 0.001), rapid progressive sperm motility
      (RPM) increased from 22 +/- 9.4 to 69 +/- 30 million/ml (P < 0.001), and sperms
      with normal morphology (NM) increased from 33 +/- 5 to 56 +/- 7 million/ml (P <
      0.001). Increment in Hb concentration was correlated significantly with LH, FSH,
      and T concentrations after IVI (r = 0.69 and r = 0.44, r = 0.75, respectively; P
      < 0.01). The increment in serum T was correlated significantly with increments in
      the TSC and total sperm motility and RPM (r = 0.66, 0.43, and 0.55, respectively;
      P < 0.001) but not with gonadotrophin levels. CONCLUSION: Our study proved for
      the first time, to our knowledge, that correction of IDA with IVI is associated
      with significant enhancement of sperm parameters and increased concentrations of
      serum LH, FSH, and T. These effects on spermatogenesis are reached by an unknown
      mechanism and suggest a number of pathways that need further human and/or
      experimental studies.

PMID- 24944925
TI  - A cross-sectional study of polycystic ovarian syndrome among adolescent and young
      girls in Mumbai, India.
AB  - INTRODUCTION: Polycystic ovary disease is a common endocrine condition which is
      rapidly gaining epidemic proportions. No community based prevalence data is
      available for this syndrome in India. MATERIALS AND METHODS: A cross-sectional
      community-based study was undertaken in a sampled census block of Mumbai to
      assess the prevalence of polycystic ovarian syndrome (PCOS) among 778 adolescents
      and young girls aged 15-24 years. Among them, 600 completed all clinical,
      ultrasonography (USG), and biochemical investigations. RESULTS: The prevalence of
      PCOS among them was 22.5% by Rotterdam and 10.7% by Androgen Excess Society
      criteria. Nonobese comprised 71.8% of PCOS diagnosed by Rotterdam criteria. Mild
      PCOS (oligomenorrhea and polycystic ovaries on USG) was the most common phenotype
      (52.6%). History of oligomenorrhea had a positive predictive value of 93.3% and
      negative predictive value of 86.7% to detect a possible case of PCOS.
      Hyperinsulinemia (serum insulin >15 MUlU/mL) was present among 19.2% of diagnosed
      PCOS cases. Obese girls with PCOS were more hirsute, hypertensive, and had
      significantly higher mean insulin and 2 h post 75 g glucose levels compared with
      nonobese PCOS. CONCLUSION: To our knowledge, this is the first urban community
      based study diagnosing PCOS and phenotypes among adolescent and young girls in
      India. This study demonstrates that PCOS is an emerging disorder during
      adolescence and screening could provide opportunity to target the group for
      promoting healthy lifestyles and early interventions to prevent future
      morbidities.

PMID- 24944926
TI  - Relationship of lipid parameters with bone mineral density in Indian population.
AB  - INTRODUCTION: Cardiovascular disease and osteoporosis share common risk factors
      including dyslipidemia. There are conflicting reports of differential relation of
      various lipid parameters on bone mineral density (BMD). Hence, we studied the
      correlation between lipid parameters and BMD in healthy adult. MATERIALS AND
      METHODS: A total of 2347 participants (male 39.4%; female 60.6%) included in this
      cross-sectional study were divided according to sex and age. Fasting blood
      samples were drawn for biochemical parameters. BMD at lumbar spine, femur, and
      forearm were measured by dual energy X-ray absorptiometry (DXA). RESULTS: In
      males, BMD at femur and lumbar spine decreased significantly with increasing
      quartiles of total cholesterol (TC) (P < 0.0001, and 0.004) and low-density
      lipoprotein cholesterol (LDL-c) (P = 0.001, and 0.01). In premenopausal women,
      BMD at femoral neck (P = 0.001) and lumbar spine (P = 0.029) showed declining
      trend with LDL-c (P = 0.007). In postmenopausal women, only BMD at total femur
      decreased significantly with TC (P = 0.024) and LDL-c (P = 0.036). All above
      findings were confirmed in correlation studies. In multiple regression analysis
      after adjusting for age, body mass index, ionized calcium, alkaline phosphatase,
      25 hydroxy vitamin D, and parathyroid hormone levels correlation of BMD with TC
      and LDL-c persisted. TC, LDL-c was higher in subjects with low bone density
      compared those with normal bone density in both sexes. CONCLUSIONS: TC and LDL-c
      had weak but significant negative correlation with BMD at femur and lumbar spine.

PMID- 24944927
TI  - Glucose homeostasis in Egyptian children and adolescents with beta-Thalassemia
      major: Relationship to oxidative stress.
AB  - BACKGROUND: Oxidative stress in children with beta-thalassemia may contribute to
      shortened life span of erythrocytes and endocrinal abnormalities. AIM: This study
      was aimed to evaluate glucose homeostasis in Egyptian children and adolescents
      with beta-thalassemia major and its relation to oxidative stress. MATERIALS AND
      METHODS: Sixty children and adolescents with beta-thalassemia major were studied
      in comparison to 30 healthy age and sex-matched subjects. Detailed medical
      history, thorough clinical examination, and laboratory assessment of oral glucose
      tolerance test (OGTT), serum ferritin, alanine transferase (ALT), fasting insulin
      levels, plasma malondialdehyde (MDA) as oxidant marker and serum total
      antioxidants capacity (TAC) were performed. Patients were divided into two groups
      according to the presence of abnormal OGTT. RESULTS: The prevalence of diabetes
      was 5% (3 of 60) and impaired glucose tolerance test (IGT) was 8% (5 of 60).
      Fasting blood glucose, 2-hour post-load plasma glucose, serum ferritin, ALT,
      fasting insulin level, homeostatic model assessment for insulin resistance index
      (HOMA-IR) and MDA levels were significantly elevated while TAC level was
      significantly decreased in thalassemic patients compared with healthy controls (P
      < 0.001 for each). The difference was more evident in patients with abnormal OGTT
      than those with normal oral glucose tolerance (P < 0.001 for each). We also
      observed that thalassemic patients not receiving or on irregular chelation
      therapy had significantly higher fasting, 2-h post-load plasma glucose, serum
      ferritin, ALT, fasting insulin, HOMA-IR, oxidative stress markers OSI and MDA
      levels and significantly lower TAC compared with either those on regular
      chelation or controls. HOMA-IR was positively correlated with age, serum
      ferritin, ALT, MDA, and negatively correlated with TAC. CONCLUSIONS: The
      development of abnormal glucose tolerance in Egyptian children and adolescents
      with beta--thalassemia is associated with alteration in oxidant-antioxidant
      status and increase in insulin resistance. RECOMMENDATION: 1- Glucose tolerance
      tests, HOMA-IR, and MDA should be an integral part of the long-term follow-up of
      children and adolescents with beta-thalassemia major. 2- Regular iron chelation
      and antioxidant therapy should be advised for thalassemic patients to improve
      glucose hemostasis.

PMID- 24944928
TI  - Association of serum paraoxonase enzyme activity and oxidative stress markers
      with dyslipidemia in obese adolescents.
AB  - OBJECTIVES: The aim of the present study was to investigate the serum paraoxonase
      1 (PON1) concentration and oxidative stress markers and assess its relations with
      the biochemical parameters in obese adolescents. MATERIALS AND METHODS: One
      hundred and fifty obese adolescents (range 16-18 years) and 150 healthy age- and
      sex-matched controls were enrolled in the study. The data were extracted from a
      project entitled "Obesity among Youth: Lifestyle and Genetic Factors" funded by
      the Science and Technology Development Fund, Egypt. Serum paraoxonase 1 (PON1),
      nitric oxide (NO), and malonaldehyde were measured. Anthropometry, fasting
      glucose, insulin concentrations, total cholesterol, high density lipoprotein
      cholesterol, low density lipoprotein-cholesterol, triglycerides, systolic and
      diastolic blood pressure (BP) were measured. Insulin resistance was determined by
      Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Diagnostic accuracy
      of oxidative markers to identify dyslipidemia was calculated with ROC analysis.
      RESULTS: The study showed that PON1 activity was significantly lower in obese
      adolescents than controls. Obese adolescents had significant lower NO level and
      significant increased MA values as compared to controls. PON1 was negatively
      correlated with MAD and body mass index in obese subjects. Obese adolescents
      showed dyslipidemia and increased blood pressure and HOMA-IR values. PON1 had
      high area under the curve in ROC analysis for identifying dyslipidemia in obese
      subjects. CONCLUSIONS: Our results indicate that obese subjects have increased
      oxidative stress and decreased PON1 activity. The lower paraoxonase level might
      contribute to the greater risk of dyslipidemia, insulin resistance, high blood
      pressure that are considered as important components in the pathogenesis of the
      metabolic syndrome in obese adolescents.

PMID- 24944929
TI  - Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a
      serological marker for juvenile onset type 1 diabetes in India.
AB  - INTRODUCTION: Zinc transporter-8 (ZnT8) is an islet cell secretory granule
      membrane protein recently identified as an autoantigen in type 1 diabetes (T1D).
      The aim of this study was to estimate the prevalence of antibodies to ZnT8
      (ZnT8A) in juvenile onset T1D and to determine the utility of ZnT8A as an
      independent marker of autoimmunity either alone in antibody-negative subjects or
      in conjunction with glutamic acid decarboxylase (GAD) and insulinoma-2 antigen
      antibodies (GADA and IA2A). RESEARCH DESIGN: ZnT8A, GADA, and IA2A were measured
      in sera of consecutive T1D patients (n = 88, age range 2-18 years) within 4 years
      of diagnosis and 88 sex-matched controls. RESULTS: The prevalences of GADA,
      ZnT8a, and IA2A were 64.7%, 31.8% and 19.3%, respectively. In newly diagnosed
      patients, the frequency of ZnT8A was 45%. ZnT8A were positive in 26% of patients
      negative for both GADA and IA2A. IA2A were positive only in two patients who were
      negative for other two antibodies. Combined use of ZnT8A and GADA could detect
      97% of antibody positive patients. In receiver operating characteristic (ROC)
      analysis, the performances of GADA and ZnT8As were better than that of IA2A; and
      AUCs of GADA, ZnT8A, and IA2A for the prediction of T1D were 0.8, 0.65, and 0.59,
      respectively. CONCLUSIONS: ZnT8A complements GADA and increases the diagnostic
      sensitivity for detection of autoimmunity in juvenile-onset T1D. Inclusion of
      ZnT8A increases the proportion of patients with antibody positivity to nearly
      80%. ZnT8A can replace IA2A as a serological marker for autoimmunity in Indian
      T1D patients without loss of sensitivity and specificity.

PMID- 24944930
TI  - Prevalence of gestational diabetes mellitus in rural Haryana: A community-based
      study.
AB  - BACKGROUND AND OBJECTIVES: Gestational diabetes mellitus (GDM) is a global health
      concern as it affects health status of both mother and fetus. In India,
      prevalence of GDM varies in different populations and no data is available from
      rural Haryana. This study was undertaken to determine the prevalence of GDM and
      risk factors associated with it in rural women of Haryana. MATERIALS AND METHODS:
      Nine hundred and thirteen women, with estimated gestational age above 24 weeks
      from a rural block of Haryana who consented to participate were given a
      standardized 2-h 75-g oral glucose tolerance test (OGTT). Pro forma containing
      general information on demographic characteristics, educational level, gravida,
      family history of diabetes, and past history of GDM was filled-up. A World Health
      Organization (WHO) criterion for 2-h 75-g OGTT was used for diagnosing GDM.
      RESULTS: GDM was diagnosed in 127/913 (13.9%) women with higher mean age as
      compared to non-GDM women. Majority (78.4%) of the women were housewives, rest
      engaged in agriculture (9.2%) and labor (5.5%). Women with gravida >=3 and
      positive family history of diabetes had significantly higher prevalence of GDM.
      History of macrosomia (birth weight >=4 kg) was significantly associated with
      prevalence of GDM (P = 0.002). On multiple logistic regression analysis, risk
      factors found to be significantly associated with GDM were maternal age >25
      years, gravida >3, history of macrosomic baby, and family history of diabetes.
      CONCLUSION: The prevalence of GDM has been found quite high in rural Haryana.
      Appropriate interventions are required for control and risk factor modifications.

PMID- 24944931
TI  - Chronic complications in newly diagnosed patients with Type 2 diabetes mellitus
      in India.
AB  - BACKGROUND: Prevalence of diabetes is on an increase in India, currently there is
      limited nation-wide data regarding the prevalence of chronic complications in
      diabetic patients at diagnosis. This information will help health-care
      professionals approach management more aggressively to prevent complications.
      OBJECTIVE: To determine the prevalence of chronic complications in newly
      diagnosed Type 2 diabetic (T2D) patients in India. DESIGN AND METHODS: This was a
      cross-sectional survey of T2D patients, diagnosed within 3 months of their first
      visit to the centers doing the survey. Each patient was screened for diabetic
      complications, hypertension, dyslipidemia, and body mass index. Family history
      was recorded. Standard protocols were used to make the diagnosis of retinopathy,
      neuropathy and nephropathy. Data analysis was carried out using the standard
      statistical techniques. RESULTS: Of the total 4,600 (males 67%, females 33%)
      newly diagnosed patients with T2D, majority were from the age group 41-50 years
      (40%). 13.15% of newly detected India T2D had neuropathy 6.1% had retinopathy and
      1.06% had nephropathy. Risk factors of macro vascular complication such as
      hypertension, obesity, and dyslipidemia were observed in 23.3%, 26%, and 27% of
      patients respectively. Ischemic heart disease was noticed in 6%. CONCLUSION: High
      prevalence of micro vascular complications was present at diagnosis along with
      association of CV cardiovascular risk factors among Indian T2D. In view of this,
      screening must be instituted for all diabetics for complications at the time of
      diagnosis itself.

PMID- 24944932
TI  - General seizures revealing macro-adenomas secreting prolactin or prolactin and
      growth hormone in men.
AB  - BACKGROUND: Epilepsy is a heterogeneous condition with numerous etiologies.
      Pituitary tumors are rarely responsible for generalized convulsions except when
      they are very large. Apart from anecdotic cases, only one study concerning
      epilepsy frequency in male macroprolactinomas is available in Medline. Our aim
      was to analyze epilepsy frequency and conditions under which seizures appear and
      disappear in men harboring macroprolactinomas or somatolactotroph adenomas.
      MATERIALS AND METHODS: We retrospectively analyzed 90 men with macro-adenomas (>1
      cm) secreting prolactin (PRL) (n = 82) or both PRL and growth hormone (n = 8) to
      look for generalized seizures. We took into account familial and personal medical
      history, clinical examination, routine and hormonal analyzes, and radiological
      assessment based on cerebral magnetic resonance imaging. RESULTS: Between 1992
      and 2012, we collected eight cases (8.9%): Seven were hospitalized for recent
      generalized seizures; one had epilepsy after conventional radiotherapy given in
      1992 because of neurosurgery failure and resistance to bromocriptine. Their
      median age was 33.75 years (22-58), median PRL was 9,198 ng/ml and median tumor
      height was 74 mm (41-110). The temporal lobe was invaded in six cases. After
      tumor reduction, epilepsy disappeared and never relapsed after a follow-up
      varying between 1 and 20 years. CONCLUSION: Epilepsy, which is a life-threatening
      condition, can be the first presentation in men with prolactinomas or
      somatolactotroph adenomas, especially those involving the supra sellar area, and
      the brain. Convulsions can also appear after radiotherapy. That one should be
      avoided, if possible, before tumor reduction by surgery or medical treatment.

PMID- 24944934
TI  - Current status of management, control, complications and psychosocial aspects of
      patients with diabetes in India: Results from the DiabCare India 2011 Study.
AB  - OBJECTIVES: DiabCare India 2011 was a cross-sectional study in patients with
      diabetes mellitus, undertaken to investigate the relationship between diabetes
      control, management and complications in a subset of urban Indian diabetes
      patients treated at referral diabetes care centres in India. MATERIALS AND
      METHODS: This was a cross-sectional, multicentre (330 centres) survey in 6168
      diabetes patients treated at general hospitals, diabetes clinics and referral
      clinics across India. Patient data, including medical and clinical examination
      reports during the past year were collected during their routine visit. The
      patients' and physicians' perceptions about diabetes management were recorded
      using a questionnaire. RESULTS: A total of 6168 subjects with diabetes (95.8%
      type 2), mean age 51.9 +/- 12.4 years and mean duration of diabetes, 6.9 +/- 6.4
      years were included. Mean HbA1c was 8.9 +/- 2.1% and the mean fasting (FPG), post
      prandial (PPG) and random (RBG) plasma glucose levels were 148 +/- 50 mg/dl 205
      +/- 66 mg/dl and 193 +/- 68mg/dl respectively. Neuropathy was the most common
      complication (41.4%); other complications were: Foot (32.7%), eye (19.7%),
      cardiovascular (6.8%) and nephropathy (6.2%). The number of diabetic
      complications increased with mean duration of diabetes. Most (93.2%) of the
      patients were on oral anti-diabetic drugs (OADs) and 35.2% were on insulin (+/
      OADs). More than 15% physicians felt that the greatest barrier to insulin therapy
      from patient's perspective were pain and fear of using injectable modality; 5.2%
      felt that the greatest barrier to insulin therapy from physician's perspective
      was the treatment cost; 4.8% felt that the major barriers to achieve optimum
      diabetic care in practice was loss to follow-up followed by lack of counselling
      (3.9%) and treatment compliance (3.6%). CONCLUSION: DiabCare India 2011 has shown
      that type 2 diabetes sets in early in Indians and glycaemic control is often sub
      optimal in these patients. These results indicate a need for more structured
      intervention at an early stage of the disease and need for increased awareness on
      benefits of good glycaemic control. It cannot be overemphasized that the status
      of diabetes care in India needs to be further improved. (ClinTrials.gov
      identifier: NCT01351922).

PMID- 24944935
TI  - Knowledge and awareness of diabetes in urban and rural India: The Indian Council
      of Medical Research India Diabetes Study (Phase I): Indian Council of Medical
      Research India Diabetes 4.
AB  - BACKGROUND: Representative data on knowledge and awareness about diabetes is
      scarce in India and is extremely important to plan public health policies aimed
      at preventing and controlling diabetes. AIM: The aim of the following study is to
      assess awareness and knowledge about diabetes in the general population, as well
      as in individuals with diabetes in four selected regions of India. MATERIALS AND
      METHODS: The study subjects were drawn from a representative sample of four
      geographical regions of India, Chandigarh, Tamil Nadu, Jharkhand and Maharashtra
      representing North, South, East and West and covering a population of 213
      million. A total of 16,607 individuals (5112 urban and 11,495 rural) aged >=20
      years were selected from 188 urban and 175 rural areas. Awareness of diabetes and
      knowledge of causative factors and complications of diabetes were assessed using
      an interviewer administered structured questionnaire in 14,274 individuals
      (response rate, 86.0%), which included 480 self-reported diabetic subjects.
      RESULTS: Only 43.2% (6160/14,274) of the overall study population had heard about
      a condition called diabetes. Overall urban residents had higher awareness rates
      (58.4%) compared to rural residents (36.8%) (P < 0.001). About 46.7% of males and
      39.6% of females reported that they knew about a condition called diabetes (P <
      0.001). Of the general population, 41.5% (5726/13,794) knew about a condition
      called diabetes. Among them, 80.7% (4620/5726) knew that the prevalence of
      diabetes was increasing, whereas among diabetic subjects, it was 93.0% (448/480).
      Among the general and diabetic population, 56.3% and 63.4% respectively, were
      aware that diabetes could be prevented. Regarding complications, 51.5% of the
      general population and 72.7% diabetic population knew that diabetes could affect
      other organs. Based on a composite knowledge score to assess knowledge among the
      general population, Tamil Nadu had the highest (31.7) and Jharkhand the lowest
      score (16.3). However among self-reported diabetic subjects, Maharashtra had the
      highest (70.1) and Tamil Nadu, the lowest score (56.5). CONCLUSION: Knowledge and
      awareness about diabetes in India, particularly in rural areas, is poor. This
      underscores the need for conducting large scale diabetes awareness and education
      programs.

PMID- 24944933
TI  - Prevalence of metabolic syndrome in the family members of women with polycystic
      ovary syndrome from North India.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most complex and common
      endocrine disorder of women in reproductive years. In addition to irregular
      menstrual cycles, chronic anovulation and hyperandrogenism, it has many metabolic
      manifestations such as obesity, hyperlipidemia, hyperinsulinemia, insulin
      resistance, dysglycemia, increased risk of cardiovascular disease or possibly
      endometrial cancer. Familial clustering of PCOS in consistence with the genetic
      susceptibility has been described. MATERIALS AND METHODS: The present study
      assessed the clinical, biochemical and hormonal parameters including prevalence
      of metabolic syndrome by two different criteria in the first- degree relatives of
      patients with PCOS. RESULTS: The average age of 37 index patients was 23 +/- 3.6
      years, with the mean age of menarche as 13.3 +/- 1.2 years. The mean age and age
      of menarche in mothers (n = 22) was 48.8 +/- 5.1 and 13 +/- 1.3 years,
      respectively, whereas as it was 23.5 +/- 4.7 and 13.3 +/- 1.2 years in sisters (n
      = 22), respectively. Metabolic syndrome (MS) defined by International Diabetes
      Federation (IDF) criteria was present in 10 index patients, 1 brother, 4 sisters,
      17 mothers and 15 fathers while as by Adult Treatment Panel III (ATP III) it was
      in 8 index patients, 5 sisters, 16 mothers and 11 fathers. CONCLUSION: The
      presence of MS or related metabolic derangements is high in the family members of
      women with PCOS.

PMID- 24944936
TI  - Assessment of anthropometric indices among residents of Calabar, South-East
      Nigeria.
AB  - BACKGROUND: Obesity is a risk factor for type 2 diabetes mellitus which may be
      addressed by application of intensive lifestyle interventions. Thus, establishing
      normative values of anthropometric indices in our environment is crucial. This
      study aimed to determine normative values of anthropometric indices of nutrition
      among residents of Calabar. MATERIALS AND METHODS: This cross sectional
      observational study recruited residents of Calabar aged between 15-79 years using
      a multistage sampling method. Trained research assistants collected socio
      demographic data and did anthropometric measurements. RESULTS: There were 645
      (56.5%) males and 489 (43.1%) females. Males had significantly lower general
      adiposity and hip circumference (HC) than females while females had significantly
      lower waist circumference (WC) and waist hip ratio (WHR) than males. The WHR
      increased with age particularly among males. Body mass index (BMI) also increased
      with age in both males and females with a peak in the middle age bracket,
      followed by a decline among the elderly. The mean (SD) BMI was 27.7 (5.0)
      kg/m(2). Males had a mean (SD) BMI of 27.0 (4.4) kg/m(2), while females had a
      mean (SD) BMI of 28.5 (5.5) kg/m(2) respectively. WC correlated positively and
      significantly with BMI and WHR in males and females. WHR correlated positively
      and significantly with BMI in males and females. CONCLUSION: There are positive
      linear inter relationships between the indices of nutrition which is strongest
      between WC and BMI. In view of the strong independent association of DM with
      indices of nutrition, it is appropriate to derive normal cut-off values for WC,
      WHR and BMI nationally.

PMID- 24944937
TI  - Waist height ratio: A universal screening tool for prediction of metabolic
      syndrome in urban and rural population of Haryana.
AB  - AIMS: To compare waist circumference (WC), body mass index (BMI), waist hip ratio
      (WHR), and waist-to-height ratio (WHtR) and define an appropriate cut-off, which
      is most closely predictive of the non-adipose components of the IDF metabolic
      syndrome (MetS) definition. METHODS AND RESULTS: A total of 3,042 adults (1,693
      in rural area and 1,349 in urban area) were screened for the presence of MetS
      according to the IDF definition. Among 3,042 adults selected as subjects, 1,518
      were male and 1,524 were female. The receiver operating curve (ROC) analysis was
      done to determine the optimal cut-off value and the best discriminatory value of
      each of these anthropometric parameters to predict two or more non-obese
      components of metabolic syndrome. The area under ROC (AURC) for WC was superior
      to that for other anthropometric variables. The optimal cut-off value of WC in
      urban and rural males was >89 cm, which is higher than that in urban and rural
      females at 83 cm and 79 cm, respectively; the optimal cut-off for WHtR was >0.51
      in rural females, 0.52 in rural males, and 0.53 in both urban males and females.
      Both parameters were found to be better than BMI and WHR. ROC and AURC values for
      WC were better than those for WHtR in men and women in both urban and rural areas
      (P = 0.0054); however, when the entire study cohort was analyzed together,
      irrespective of gender and place of residence, then at a value of 0.52, WHtR
      scored over WC as a predictor of metabolic syndrome (P = 0.001). CONCLUSION:
      Although the predictive value of different gender-specific WC values is clearly
      superior to other anthropometric measures for predicting two or more non-adipose
      components of MetS, a single value of WHtR irrespective of gender and the area of
      residence can be used as a universal screening tool for the identification of
      individuals at high risk of development of metabolic complications.

PMID- 24944938
TI  - Clinical profile, outcomes, and progression to type 2 diabetes among Indian women
      with gestational diabetes mellitus seen at a diabetes center in south India.
AB  - AIM: To describe the clinical profile, maternal and fetal outcomes, and the
      conversion rates to diabetes in women with gestational diabetes mellitus (GDM)
      seen at a tertiary care diabetes center in urban south India. MATERIALS AND
      METHODS: Clinical case records of 898 women with GDM seen between 1991 and 2011
      were extracted from the Diabetes Electronic Medical Records (DEMR) of a tertiary
      care diabetes center in Chennai, south India and their clinical profile was
      analyzed. Follow-up data of 174 GDM women was available. To determine the
      conversion rates to diabetes, oral glucose tolerance test (OGTT) was done in
      these women. Glucose tolerance status postpartum was classified based on World
      Health Organization (WHO) 2006 criteria. RESULTS: The mean maternal age of the
      women was 29 +/- 4 years and mean age of gestation at first visit were 24 +/- 8.4
      weeks. Seventy percent of the women had a family history of diabetes. Seventy
      eight percent of the women delivered full-term babies and 65% underwent a
      cesarean section. The average weight gain during pregnancy was 10.0 +/- 4.2 kg.
      Macrosomia was present in 17.9% of the babies, hypoglycemia in 10.4%, congenital
      anomalies in 4.3%, and the neonatal mortality rate was 1.9%. Mean follow-up
      duration of the 174 women of whom outcome data was available was 4.5 years. Out
      of the 174, 101 women who were followed-up developed diabetes, of whom half
      developed diabetes within 5 years and over 90%, within 10 years of the delivery.
      CONCLUSIONS: Progression to type 2 diabetes mellitus (T2DM) in Indian women with
      GDM is rapid. There is an urgent need to develop standardized protocols for GDM
      care in India that can improve the maternal and fetal outcomes and help prevent
      future diabetes in women with GDM.

PMID- 24944939
TI  - Diabetic retinopathy in acromegaly.
AB  - INTRODUCTION: Although growth hormone (GH) has been implicated in the
      pathogenesis of diabetic retinopathy (DR), DR is deemed to be rare in patients
      with GH excess. Our aim was to study its prevalence in subjects with acromegaly
      suffering from diabetes mellitus (DM), to analyze its characteristics, and to
      look for predictive factors such as age at diagnosis, GH concentration and
      duration, DM duration, DM control, and family background. MATERIALS AND METHODS:
      Forty patients with acromegaly and DM (21 males, 19 females), median age = 50
      years, underwent a systematic ophthalmological examination with dilated
      funduscopy to seek diabetic retinopathy. RESULTS: Among this population, 05
      (12.5%) had DR. It was at an early stage or background retinopathy in 3 cases and
      at a more advanced stage or proliferative retinopathy in 2 cases. We did not find
      any correlation with age at diagnosis, GH levels and duration, DM duration and
      family history of DM, but poor glycemic control seems to play a role although
      statistical analysis showed borderline significance. CONCLUSION: From this study,
      we conclude that prevalence of DR in patients with acromegaly is 12.5%, and it is
      slight or moderate. Among studied factors, only poor glycemic control seems to be
      implicated in its development.

PMID- 24944940
TI  - Our experience with papillary thyroid microcancer.
AB  - BACKGROUND: Papillary thyroid microcarcinoma (PTMC) describes a focus of
      papillary thyroid cancer that is less than 1 cm in size. These tumors are
      frequently found on histopathological examination of thyroid specimens, operated
      upon for an indication other than suspected malignancy. MATERIALS AND METHODS:
      From 2005 to 2012, 94 of 1300 thyroidectomy specimens in our institution were
      found to have PTMC. Of these, 77 were isolated PTMC while the others were
      associated with other differentiated cancers. We studied their clinicopathologic
      features, treatment and long-term outcome. RESULTS: There were 18 men and 59
      women (the male: female ratio was 1:3), their mean age was 44 +/- 10.5 years
      (range: 18-72 years). Multinodular goiter was the most common indication for
      surgery. Malignancy was suspected in only 31.4% cases. The mean tumor size was
      4.1 +/- 2.3 mm. Nearly 17% cases had slightly larger tumors measuring >6 but <10
      mm. Multifocal tumor was found in 44.1% of cases and among these, multifocal
      disease restricted to a single lobe was found in 19.5%. Eleven patients (14.2%)
      had cervical lymph node metastasis, 3 (3.9%) had extra thyroid tumor extension
      and 2 (2.6%) had evidence of vascular invasion. One patient (1.3%) presented with
      bone metastasis. Majority of the patients (79.2%) underwent total thyroidectomy
      with or without lymph node dissection. Sixteen patients (20.7%) who had initially
      undergone hemithyroidectomy went on to have completion thyroidectomy. Twenty nine
      patients (36.8%) also received radioactive iodine. The mean duration of follow-up
      was 20.2 +/- 13.5 months. On follow-up one patient developed cervical lymph node
      recurrence and one died due to a second malignancy. CONCLUSIONS: PTMC is often
      found as an incidental finding on the thyroidectomy specimen. Sometimes they
      present with regional lymph node metastasis and very rarely with distant
      metastasis. They have a good prognosis similar to papillary thyroid carcinoma.

PMID- 24944941
TI  - Risk of developing adulthood obesity among females born with low birth weight:
      Results from a non-concurrent study from rural Southern India.
AB  - OBJECTIVE: To determine the relationship between birth weight and the evolution
      of obesity in adult life in women from a rural developmental block in southern
      India. DESIGN: Non-concurrent cohort. SETTING: General community- a rural
      developmental block in southern India. PARTICIPANTS: Two hundred and seventy one
      young healthy females were recruited from a birth cohort. The study subjects were
      98 women in the age group of 19-23 years who had been born with low birth weight
      (LBW) and 173 women in the same age group who had been born with normal birth
      weight (NBW). MATERIALS AND METHODS: Data collection involved interview using a
      structured questionnaire and anthropometric measurements. ANALYSIS: Chi-square
      test to assess significance of association, independent sample t test to assess
      the difference between means, odds ratios for measuring magnitude of association,
      stratified analysis to identify various interactions and confounders, and
      multiple logistic regression models to identify the relationship between birth
      weight and young adult obesity (BMI > 25). RESULTS: A crude odds ratio of 0.564
      (95% CI 0.262 - 1.214) was obtained for the association between LBW and
      development of obesity later in life. In the final logistic regression model, it
      was found that a young adult female with low birth weight who belonged to a
      higher socio-economic group had a higher risk of developing obesity (Adjusted
      odds for the interaction term between LBW and high SES 6.251; 95% CI 1.236 -
      31.611). CONCLUSION: The study could not find any significant association between
      LBW and development of obesity later in life, but it found a higher probability
      of developing obesity later in life among low birth weight female children born
      in high socio-economic status families.

PMID- 24944942
TI  - Status of iodine deficiency disorder in district Udham Singh Nagar, Uttarakhand
      state India.
AB  - BACKGROUND: Iodine deficiency disorder (IDD) is a public health problem in
      Uttarakhand state. OBJECTIVE: The present study was conducted in district Udham
      Singh Nagar, Uttarakhand state with an objective to assess the status of iodine
      deficiency amongst school age children (6-12 years). MATERIALS AND METHODS:
      Thirty clusters were selected by utilizing the population proportionate to size
      (PPS) cluster sampling methodology. A total of 1807 children in the age group of
      6-12 years were included. The clinical examination of the thyroid of each child
      was conducted. Urine and Salt samples were collected from children. RESULTS: The
      Total Goiter Rate (TGR) was found to be 13.2%. The proportion of children with
      Urinary Iodine Excretion (UIE) level <20, 20-49, 50-99, 100-199 and >=200 MUg/l
      was found to be nil, 6.0, 21.2, 34.2 and 38.5 percent, respectively. The median
      UIE level was 150 MUg/l. Only 46.7% of the salt samples had stipulated level of
      iodine of 15 ppm and more. CONCLUSION: The study population had mild degree of
      public health problem of iodine deficiency.

PMID- 24944943
TI  - Interventional endocrinology: A futuristic perspective.
AB  - Interventions in endocrinology make a huge impact on life of patients with
      endocrine diseases. This brief communication discusses the role played by both
      medical and surgical interventions in practice of endocrinology. Endocrinology is
      branch of medicine where treatment is as close to ideal as possible. For people
      with hormone deficiencies, medical intervention in form of replacement with
      hormones generated by recombinant technologies is a perfectly natural treatment.
      Hormone excess is also being evaluated and treated with exceedingly precise
      surgical interventions with minimal morbidity. 

PMID- 24944945
TI  - Is it necessary to rename gestational diabetes mellitus?

PMID- 24944944
TI  - A retrospective study on finding correlation of pioglitazone and incidences of
      bladder cancer in the Indian population.
AB  - OBJECTIVES: This retrospective cohort study analyzed the clinical data of cancer
      patients conducted in a cancer hospital, Chennai to assess the correlation (if
      any) between use of antidiabetic agents including pioglitazone and the incidence
      of bladder cancer. MATERIALS AND METHODS: Totally, 5079 cancer patients' with and
      without diabetes were included and analyzed in this retrospective study. RESULTS:
      A total of 1077 patient data were screened out of a total of 5079. A total of 20
      patients were found to have bladder cancer. Out of 1077 patients, 31 were
      pioglitazone users on the drug for not less than 2 years. The remaining 1046 were
      on other drugs other than pioglitazone. It is observed that 1 out of 31 developed
      bladder cancer in the pioglitazone group 19 out of 1046 developed bladder cancer
      in the nonpioglitazone group. The result of the analysis indicates that there is
      no significant (P = 0.918) association between pioglitazone and bladder cancer.
      CONCLUSION: In this retrospective study, the number of diabetic patients on
      pioglitazone with bladder cancer was fewer than the diabetic patients on other
      medications with the disease. Further, no link could be established between any
      specific drug use and bladder cancer. Least number of patients with bladder
      cancer was on pioglitazone, suggesting that pioglitazone alone cannot be
      considered a cause for increased incidence of bladder cancer in diabetic
      patients.

PMID- 24944946
TI  - Proteus syndrome: More vigilance needed to diagnose it.

PMID- 24944947
TI  - A very rare cohort of elderly patients with autoimmune polyglandular syndrome
      type 3b.

PMID- 24944948
TI  - Primary hypothyroid induced by drug interaction.

PMID- 24944949
TI  - Catecholamine induced cardiomyopathy in phaeochromocytoma.

PMID- 24944950
TI  - Comparison of the world health organization and the international association of
      diabetes and pregnancy study groups criteria in diagnosing gestational diabetes
      mellitus in South Indians.

PMID- 24944951
TI  - Is metabolic syndrome prevailing in Iraqi children?

PMID- 24944952
TI  - Prevalence of thyroid function test abnormalities and thyroid autoantibodies in
      children with vitiligo.

PMID- 24944953
TI  - Primary hyperparathyroidism and malignancy: Forgotten friends or new
      aquaintances.

PMID- 24944954
TI  - Pachydermoperisotosis.

PMID- 24944955
TI  - Response to the study by V. Kumaravel et al., titled "Are the current Indian
      growth charts really representative?".

PMID- 24944956
TI  - Author reply.

PMID- 24944957
TI  - Effect of titanium and stainless steel posts in detection of vertical root
      fractures using NewTom VG cone beam computed tomography system.
AB  - PURPOSE: Vertical root fracture (VRF) is a common complication in endodontically
      treated teeth. Considering the poor prognosis of VRF, a reliable and valid
      detection method is necessary. Cone beam computed tomography (CBCT) has been
      reported to be a reliable tool for the detection of VRF; however, the presence of
      metallic intracanal posts can decrease the diagnostic values of CBCT systems.
      This study evaluated and compared the effects of intracanal stainless steel or
      titanium posts on the sensitivity, specificity, and accuracy of VRF detection
      using a NewTom VG CBCT system. MATERIALS AND METHODS: Eighty extracted single
      rooted teeth were selected and sectioned at the cemento-enamel junction. The
      roots were divided into two groups of 40. Root fracture was induced in the test
      group by using an Instron machine, while the control group was kept intact. Roots
      were randomly embedded in acrylic blocks and radiographed with the NewTom VG,
      both with titanium and stainless steel posts and also without posts. Sensitivity,
      specificity, and accuracy values were calculated as compared to the gold
      standard. RESULTS: The sensitivity, specificity, and accuracy of VRF diagnosis
      were significantly lower in teeth with stainless steel and titanium posts than in
      those without posts. Interobserver agreement was the highest in teeth without
      posts, followed by stainless steel posts, and then titanium posts. CONCLUSION:
      Intracanal posts significantly decreased the VRF diagnostic values of CBCT. The
      stainless steel posts decreased the diagnostic values more than the titanium
      posts.

PMID- 24944958
TI  - Comparison of the reproducibility of panoramic radiographs between dentulous and
      edentulous patients.
AB  - PURPOSE: This study was performed to evaluate the reproducibility of panoramic
      radiographs of dentulous and edentulous patients. MATERIALS AND METHODS: The
      reproducibility of panoramic radiographs was evaluated using the panoramic
      radiographs acquired from 30 anterior dentulous patients by using a common biting
      positioning device (dentulous group) and 30 anterior edentulous patients by using
      chin-support devices to take a panoramic radiograph (edentulous group),
      respectively; these patients had undergone 3 or more panoramic radiographs. The
      widths and angles between the designated landmarks were measured on the panoramic
      radiographs, and the reproducibility was evaluated using the intraclass
      correlation coefficient (ICC) and the coefficient of variation. RESULTS: In the
      dentulous and edentulous groups, the ICCs of the mandibular ramus and mandibular
      angle areas were higher than the condylar head and zygomatic areas. The
      mandibular ramus and angle areas showed statistically lower mean coefficients of
      variation than the condylar head and zygomatic areas in the dentulous group. The
      mandibular angle area showed a significantly lower mean coefficient of variation
      than the zygomatic area in the edentulous group. By comparing the two groups,
      each ICC of the edentulous group was lower than that of the dentulous group, and
      the mean coefficients of variation of the mandibular ramus area, zygomatic area,
      left condylar inclination, and ramus ratio between the right and the left in the
      edentulous group were significantly higher than those in the dentulous group.
      CONCLUSION: Biting positioning for dentulous patients provided better positioning
      reproducibility than chin-support positioning when performing panoramic
      radiography for edentulous patients.

PMID- 24944959
TI  - Development of dental charts according to tooth development and eruption for
      Turkish children and young adults.
AB  - PURPOSE: In this study, we aimed to develop dental charts for Turkish children
      and young adults of both genders within the age group of 4.5-22.5 years according
      to tooth mineralization and eruption in a format similar to that proposed by
      AlQahtani et al. MATERIALS AND METHODS: In total, 753 digital panoramic
      radiographs from 350 males and 403 females were assessed. The permanent teeth
      were evaluated according to the classification system described by Demirjian et
      al. The eruption stage was assessed with Bengston's system, which was modified by
      AlQahtani et al at four points. RESULTS: Teeth generally developed earlier in
      females than in males. This was particularly notable in the age group of 5-14
      years. However, this difference was usually visible in only one stage, not in all
      teeth. It has been determined that the mixed dentition period ended with the
      shedding of the second deciduous molars in both genders. CONCLUSION: The dental
      charts presented here included information that could be beneficial to dental
      clinicians in making appropriate diagnosis and planning orthodontic and surgical
      procedures. These charts also provided datasets for preliminary dental age
      estimation in Turkish children and young adults.

PMID- 24944960
TI  - A comparative study of cone-beam computed tomography and digital periapical
      radiography in detecting mandibular molars root perforations.
AB  - PURPOSE: The aim of this in vitro study was to determine the sensitivity and
      specificity of cone-beam computed tomography (CBCT) and digital periapical
      radiography in the detection of mesial root perforations of mandibular molars.
      MATERIALS AND METHODS: In this in vitro study, 48 mandibular molars were divided
      into 4 groups. First, the mesial canals of all the 48 teeth were endodontically
      prepared. In 2 groups (24 teeth each), the roots were axially perforated in the
      mesiolingual canal 1-3 mm below the furcation region, penetrating the root
      surface ("root perforation"). Then, in one of these 2 groups, the mesial canals
      were filled with gutta-percha and AH26 sealer. Mesial canals in one of the other
      2 groups without perforation (control groups) were filled with the same
      materials. The CBCT and periapical radiographs with 3 different angulations were
      evaluated by 2 oral and maxillofacial radiologists. The specificity and
      sensitivity of the two methods were calculated, and P<0.05 was considered
      significant. RESULTS: The sensitivity and specificity of CBCT scans in the
      detection of obturated root canal perforations were 79% and 96%, respectively,
      and in the case of three-angled periapical radiographs, they were 92% and 100%,
      respectively. In non-obturated root canals, the sensitivity and specificity of
      CBCT scans in perforation detection were 92% and 100%, respectively, and for
      three-angled periapical radiographs, they were 50% and 96%, respectively.
      CONCLUSION: For perforation detection in filled-root canals, periapical
      radiography with three different horizontal angulations would be trustworthy, but
      it is recommended that CBCT be used for perforation detection before obturating
      root canals.

PMID- 24944961
TI  - Does cone-beam CT alter treatment plans? Comparison of preoperative implant
      planning using panoramic versus cone-beam CT images.
AB  - PURPOSE: The present study was performed to compare the planning of implant
      placement based on panoramic radiography (PAN) and cone-beam computed tomography
      (CBCT) images, and to study the impact of the image dataset on the treatment
      planning. MATERIALS AND METHODS: One hundred five partially edentulous patients
      (77 males, 28 females, mean age: 46 years, range: 26-67 years) seeking oral
      implant rehabilitation were referred for presurgical imaging. Imaging consisted
      of PAN and CBCT imaging. Four observers planned implant treatment based on the
      two-dimensional (2D) image datasets and at least one month later on the three
      dimensional (3D) image dataset. Apart from presurgical diagnostic and dimensional
      measurement tasks, the observers needed to indicate the surgical confidence
      levels and assess the image quality in relation to the presurgical needs.
      RESULTS: All observers confirmed that both imaging modalities (PAN and CBCT) gave
      similar values when planning implant diameter. Also, the results showed no
      differences between both imaging modalities for the length of implants with an
      anterior location. However, significant differences were found in the length of
      implants with a posterior location. For implant dimensions, longer lengths of the
      implants were planned with PAN, as confirmed by two observers. CBCT provided
      images with improved scores for subjective image quality and surgical confidence
      levels. CONCLUSION: Within the limitations of this study, there was a trend
      toward PAN-based preoperative planning of implant placement leading towards the
      use of longer implants within the posterior jaw bone.

PMID- 24944962
TI  - Assessment of trabecular bone changes around endosseous implants using image
      analysis techniques: A preliminary study.
AB  - PURPOSE: The objective of this study was to assess the trabecular bone changes
      that occurred around functional endosseous dental implants by means of
      radiographic image analysis techniques. MATERIALS AND METHODS: Immediate
      preoperative and postoperative periapical radiographs of de-identified implant
      patients at the University Dental Hospital of Manchester were retrieved, screened
      for specific inclusion criteria, digitized, and quantified for structural
      elements of the trabecular bone around the endosseous implants, by using image
      analysis techniques. Data were analyzed using SPSS version 11.5. P values of less
      than 0.05 were considered statistically significant. RESULTS: A total of 12
      implants from 11 patients were selected for the study, and 26 regions of interest
      were obtained. There was a significant increase in the bone area in terms of the
      mean distance between nodes (p=0.006) and a significant decrease in the marrow
      area in terms of the bone area (p=0.006) and the length of marrow spaces
      (p=0.032). CONCLUSION: It appeared that the bone around the implant underwent
      remodeling that resulted in a net increase in bone after implant placement.

PMID- 24944963
TI  - Interobserver agreement on the diagnosis of carotid artery calcifications on
      panoramic radiographs.
AB  - PURPOSE: This study was performed to investigate the interobserver agreement on
      the detection of carotid artery calcifications on panoramic radiographs.
      MATERIALS AND METHODS: This study consisted of panoramic radiographs acquired
      from 634 male patients of the age of 50 years or older. Having excluded carotids
      of no diagnostic quality, 1008 carotids from the panoramic radiographs of the
      patients were interpreted by two oral and maxillofacial radiologists
      independently for the presence of carotid artery calcifications. Statistical
      analysis was used to calculate the interobserver agreement. RESULTS:
      Interobserver agreement was obtained for 932 carotids (92.4%). Inconsistent
      interpretation of 76 carotids (7.5%) between the two observers was found. Cohen's
      kappa value was 0.688 (p<0.001). CONCLUSION: The probability of a match between
      the two observers was substantially high.

PMID- 24944964
TI  - Comparison of alveolar ridge preservation methods using three-dimensional micro
      computed tomographic analysis and two-dimensional histometric evaluation.
AB  - PURPOSE: This study evaluated the efficacy of alveolar ridge preservation methods
      with and without primary wound closure and the relationship between histometric
      and micro-computed tomographic (CT) data. MATERIALS AND METHODS: Porcine
      hydroxyapatite with polytetrafluoroethylene membrane was implanted into a canine
      extraction socket. The density of the total mineralized tissue, remaining
      hydroxyapatite, and new bone was analyzed by histometry and micro-CT. The
      statistical association between these methods was evaluated. RESULTS: Histometry
      and micro-CT showed that the group which underwent alveolar preservation without
      primary wound closure had significantly higher new bone density than the group
      with primary wound closure (P<0.05). However, there was no significant
      association between the data from histometry and micro-CT analysis. CONCLUSION:
      These results suggest that alveolar ridge preservation without primary wound
      closure enhanced new bone formation more effectively than that with primary wound
      closure. Further investigation is needed with respect to the comparison of
      histometry and micro-CT analysis.

PMID- 24944965
TI  - The effectiveness of a pre-procedural mouthrinse in reducing bacteria on
      radiographic phosphor plates.
AB  - PURPOSE: This study assessed the effectiveness of three antimicrobial mouthrinses
      in reducing microbial growth on photostimulable phosphor (PSP) plates. MATERIALS
      AND METHODS: Prior to performing a full-mouth radiographic survey (FMX), subjects
      were asked to rinse with one of the three test rinses (Listerine(r),
      Decapinol(r), or chlorhexidine oral rinse 0.12%) or to refrain from rinsing. Four
      PSP plates were sampled from each FMX through collection into sterile containers
      upon exiting the scanner. Flame-sterilized forceps were used to transfer the PSP
      plates onto blood agar plates (5% sheep blood agar). The blood agar plates were
      incubated at 37C for up to 72 h. An environmental control blood agar plate was
      incubated with each batch. Additionally, for control, 25 gas-sterilized PSP
      plates were plated onto blood agar and analyzed. RESULTS: The mean number of
      bacterial colonies per plate was the lowest in the chlorhexidine group, followed
      by the Decapinol, Listerine, and the no rinse negative control groups. Only the
      chlorhexidine and Listerine groups were significantly different (p=0.005). No
      growth was observed for the 25 gas-sterilized control plates or the environmental
      control blood agar plates. CONCLUSION: The mean number of bacterial colonies was
      the lowest in the chlorhexidine group, followed by the Decapinol, Listerine, and
      the no rinse groups. Nonetheless, a statistically significant difference was
      found only in the case of Listerine. Additional research is needed to test
      whether a higher concentration (0.2%) or longer exposure period (two consecutive
      30 s rinse periods) would be helpful in reducing PSP plate contamination further
      with chlorhexidine.

PMID- 24944966
TI  - Use of a gesture user interface as a touchless image navigation system in dental
      surgery: Case series report.
AB  - PURPOSE: The purposes of this study were to develop a workstation computer that
      allowed intraoperative touchless control of diagnostic and surgical images by a
      surgeon, and to report the preliminary experience with the use of the system in a
      series of cases in which dental surgery was performed. MATERIALS AND METHODS: A
      custom workstation with a new motion sensing input device (Leap Motion) was set
      up in order to use a natural user interface (NUI) to manipulate the imaging
      software by hand gestures. The system allowed intraoperative touchless control of
      the surgical images. RESULTS: For the first time in the literature, an NUI system
      was used for a pilot study during 11 dental surgery procedures including tooth
      extractions, dental implant placements, and guided bone regeneration. No
      complications were reported. The system performed very well and was very useful.
      CONCLUSION: The proposed system fulfilled the objective of providing touchless
      access and control of the system of images and a three-dimensional surgical plan,
      thus allowing the maintenance of sterile conditions. The interaction between
      surgical staff, under sterile conditions, and computer equipment has been a key
      issue. The solution with an NUI with touchless control of the images seems to be
      closer to an ideal. The cost of the sensor system is quite low; this could
      facilitate its incorporation into the practice of routine dental surgery. This
      technology has enormous potential in dental surgery and other healthcare
      specialties.

PMID- 24944967
TI  - Central mucoepidermoid carcinoma of the maxilla with unusual ground glass
      appearance and calcifications: A case report.
AB  - Mucoepidermoid carcinomas (MECs) arising within the jaws as primary central bony
      lesions are termed central MECs. Central MECs are extremely rare, comprising 2-3%
      of all mucoepidermoid carcinomas. We herein report a rare case of central MEC of
      the maxilla in a 52-year-old male whose plain radiographs showed a "ground glass"
      pattern and computed tomographic images, a hypodense mass with numerous
      calcifications. To the best of our knowledge, this is the first report of central
      MEC showing a "ground glass" appearance. 

PMID- 24944968
TI  - Clival lesion incidentally discovered on cone-beam computed tomography: A case
      report and review of the literature.
AB  - An osteolytic lesion with a small central area of mineralization and sclerotic
      borders was discovered incidentally in the clivus on the cone-beam computed
      tomography (CBCT) of a 27-year-old male patient. This benign appearance indicated
      a primary differential diagnosis of non-aggressive lesions such as fibro-osseous
      lesions and arrested pneumatization. Further, on magnetic resonance imaging
      (MRI), the lesion showed a homogenously low T1 signal intensity with mild
      internal enhancement after post-gadolinium and a heterogeneous T2 signal
      intensity. These signal characteristics might be attributed to the fibrous
      tissues, chondroid matrix, calcific material, or cystic component of the lesion;
      thus, chondroblastoma and chondromyxoid fibroma were added to the differential
      diagnosis. Although this report was limited by the lack of final diagnosis and
      the patient lost to follow-up, the incidental skull base finding would be
      important for interpreting the entire volume of CBCT by a qualified oral and
      maxillofacial radiologist. 

PMID- 24944969
TI  - An alternative approach to extruding a vertically impacted lower third molar
      using an orthodontic miniscrew: A case report with cone-beam CT follow-up.
AB  - One of the most common oral surgical procedures is the extraction of the lower
      third molar (LTM). Postoperative complications such as paresthesia due to
      inferior alveolar nerve (IAN) injury are commonly observed in cases of horizontal
      and vertical impaction. The present report discusses a case of a vertically
      impacted LTM associated with a dentigerous cyst. An intimate contact between the
      LTM roots and the mandibular canal was observed on a panoramic radiograph and
      confirmed with cone-beam computed tomographic (CBCT) cross-sectional cuts. An
      orthodontic miniscrew was then used to extrude the LTM prior to its surgical
      removal in order to avoid the risk of inferior alveolar nerve injury. CBCT
      imaging follow-up confirmed the success of the LTM orthodontic extrusion. 

PMID- 24944970
TI  - Diagnosis, causes and treatments of instability following total knee
      arthroplasty.
AB  - Instability following total knee arthroplasty is one of the major causes of
      revision surgery. In most cases, it can be prevented by using an appropriate
      prosthesis and a good surgical technique. Particular attention should be given to
      confirmation of diagnosis for which thorough history taking, complete physical
      examination and radiographic evaluation are needed. With regard to treatment,
      identification of the etiology of instability is crucial for establishing proper
      treatment plans; instability would persist without correction of the cause of the
      initial instability. For successful revision surgery, balanced medio-lateral and
      flexion-extension gaps should be achieved. Constrained or rotating-hinge total
      knee prosthesis should also be considered as an alternative option for certain
      subsets of patients with instability. 

PMID- 24944972
TI  - Flexion Gap Measured in 45 Degrees and 90 Degrees of Hip Flexion Positions during
      Total Knee Arthroplasty: Measurement by Navigation System.
AB  - PURPOSE: To evaluate the influence of thigh weight in different hip flexion
      positions on the knee flexion gap in total knee arthroplasty (TKA). MATERIALS AND
      METHODS: We evaluated 20 patients (25 knees) with osteoarthritis of the knee that
      underwent TKA using a navigation system from May 2010 to April 2011. After
      posterior cruciate ligament sacrificing, complete soft tissue balancing, and
      fixation of all components with cement, the flexion gaps were measured with the
      patello-femoral joint reduced. Medial and lateral flexion gaps were measured
      separately in both the 90 degrees -90 degrees  and 45 degrees -90 degrees 
      flexion positions of the hip-knee joints. RESULTS: The medial and lateral flexion
      gaps in the 45 degrees -90 degrees  flexion position of the hip-knee joints were
      13.02+/-2.17 mm and 13.12+/-2.21 mm, respectively. The medial and lateral flexion
      gaps in the 90 degrees -90 degrees  flexion position were 12.92+/-2.03 mm and
      13.08+/-2.29 mm, respectively. The flexion gaps showed no significant (p>0.05)
      differences between the two different hip flexion positions. CONCLUSIONS: Flexion
      gaps in TKA were not influenced by hip flexion positions (45 degrees  or 90
      degrees  of flexion). Therefore, soft tissue balancing and polyethylene thickness
      should not be affected by hip flexion positions during TKA.

PMID- 24944973
TI  - Implant Overhang after Unicompartmental Knee Arthroplasty: Oxford Prosthesis
      versus Miller-Galante II Prosthesis.
AB  - PURPOSE: The purpose of the present study is to compare the prevalence of implant
      overhang between the Oxford and the Miller-Galante II (M-G II) unicompartmental
      knee arthroplasty (UKA) prostheses and determine whether overhang is associated
      with postoperative clinical results. MATERIALS AND METHODS: We retrospectively
      reviewed one hundred and seven UKAs which consisted of 37 Oxford UKAs and 70 M-G
      II. Overhang was considered present if >=3 mm overhang was observed in any zone.
      The range of motion, the Knee Society scores and the Western Ontario and McMaster
      scores were compared after a mean follow-up duration of 48 months. RESULTS:
      Thirty three of 107 knees (30.8%) had overhang in at least one zone of the
      femoral or tibial component. In the tibial side, there were no significant
      differences between the groups in component overhang in each zone. In the femoral
      side, the Oxford UKA group showed a significantly higher prevalence of the
      posterior overhang of the femoral component (19/37, 51.4%) than did the M-G II
      UKA group (3/70, 4.3%; p<0.001). However, no significant differences in clinical
      results were observed between the two groups. There were also no significant
      differences in clinical results between the overhang and the non-overhang groups.
      CONCLUSIONS: Posterior overhang of the femoral component was highly prevalent in
      Oxford UKA patients. However, posterior overhang of the femoral component had no
      significant relationship with postoperative clinical results in both Oxford and M
      G II UKAs at a mean of 48 months follow-up.

PMID- 24944971
TI  - Meniscal repair.
AB  - The meniscus has several important roles, such as transmission of the load,
      absorption of the shock in the knee joint, acting as a secondary anteroposterior
      stabilizer of the knee joint, and contributing to proprioception of the knee
      joint. Degenerative changes of the knee joint develop in the long-term follow-up
      even after partial meniscectomy. Thus, there has been growing interest in
      meniscal repair. In addition, with increased understanding of the important roles
      of the meniscal root and advancement of diagnostic methods, efforts have been
      made to ensure preservation of the meniscal roots. In this review article, we
      will discuss operative techniques and clinical outcomes of arthroscopic repair of
      the meniscus and the meniscal root and postoperative rehabilitation and
      complications as well. 

PMID- 24944974
TI  - Corrective tibial osteotomy in young adults using an intramedullary nail.
AB  - PURPOSE: The purpose of this study was to document results of a less invasive
      technique of open wedge proximal tibial osteotomy (PTO) for the varus knee in
      young adults using an intramedullary tibial nail. MATERIALS AND METHODS: We
      prospectively studied 24 knees in 16 young patients with varus knee deformity.
      The mean follow-up was 54 months (range, 36 to 107 months) and the mean age of
      patients at the time of operation was 25.8 years (range, 18 to 40 years). The
      open wedge PTO was performed below tibial tuberosity using a percutaneous
      multiple drill-hole technique. Conventional intramedullary tibial nail was used
      for fixation without bone graft. Radiographic evaluations were made using
      mechanical alignment (MA), posterior tibial slope angle, and Insall-Salvati
      ratio. Union time, loss of correction, implant failure, and associated
      complications were also investigated. RESULTS: The mean MA was significantly
      changed from -9.7 degrees  preoperatively to 1.1 degrees  at the final follow-up
      (p<0.001). There was no significant change in the proximal tibial anatomy and
      patellar height. All patients achieved radiographic bony union at an average of
      3.1 months without loss of correction. The only complication was knee pain due to
      nail prominence in 3 patients. CONCLUSIONS: Radiographic evaluation indicated
      that PTO using an intramedullary tibial nail leads to significant improvement in
      radiographic parameters without changes in posterior tibial slope or patellar
      height. We found that this technique could be a less invasive and effective
      alternative for correction of the varus knee in young adults.

PMID- 24944975
TI  - Anatomic Single Bundle Anterior Cruciate Ligament Reconstruction by Low Accessory
      Anteromedial Portal Technique: An In Vivo 3D CT Study.
AB  - PURPOSE: Proper femoral tunnel position is important for anatomical
      reconstruction of the anterior cruciate ligament (ACL). The purpose of this study
      was to evaluate the positions of femoral and tibial tunnels created using an
      accessory anteromedial portal technique in single bundle ACL reconstruction.
      MATERIALS AND METHODS: The femoral tunnel was targeted at the mid-portion of the
      ACL bundles. We evaluated postoperative computed tomography scans of 32 patients
      treated by ACL reconstruction using a free-hand low accessory anteromedial portal
      technique. On the tibial side, the tunnel position was evaluated using Tsukada's
      method. On the femoral side, the position was evaluated using 1) the quadrant
      method, 2) Mochizuki's method, 3) Mochizuki's method, and 4) Takahashi's method.
      Tunnel obliquity was also evaluated. RESULTS: The mean tibial tunnel position was
      located at 44.6%+/-2.5% anterior from the anterior margin and 48.0%+/-3.0% in
      medial from the medial margin. The mean femoral tunnel position was located at
      the center between the anteromedial and posterolateral bundles: Quadrant method,
      26.7%+/-2.7%/30.0%+/-2.9%; Watanabe's method, 37.7%+/-2.5%/26.6%+/-2.2%;
      Mochizuki's method, 38.7%+/-2.7%; Takahashi's method, 21.8%+/-2.2%. The mean
      femoral tunnel obliquity was 57.7 degrees +/-6.2 degrees  in the sagittal plane
      and 49.9 degrees +/-5.6 degrees  in the coronal plane. CONCLUSIONS: In anatomic
      single bundle ACL reconstruction, the low anteromedial portal technique can
      restore accurate position of the native footprint. Accurate femoral tunnel
      position facilitates recovery of stability and decreases graft failure rate.

PMID- 24944976
TI  - Second-look arthroscopic assessment and clinical results of modified pull-out
      suture for posterior root tear of the medial meniscus.
AB  - PURPOSE: To identify the structural integrity of the healing site after
      arthroscopic repair of a posterior root tear of the medial meniscus by second
      look arthroscopy and to determine the clinical relevance of the findings.
      MATERIALS AND METHODS: From January 2005 to December 2010, 20 consecutive
      patients underwent arthroscopic modified pull-out suture repair for a posterior
      root tear of the medial meniscus. Thirteen patients were available for second
      look arthroscopic evaluation. The healing status of the medial meniscus was
      classified as complete healing, lax healing, scar tissue healing, and failed
      healing. We evaluated the correlation between the clinical symptoms and second
      look arthroscopic findings. Clinical evaluation was based on the Lysholm knee
      scores and Hospital for Special Surgery (HSS) scores. RESULTS: There were 4 cases
      of complete healing, 4 lax healing, 4 scar tissue healing, and 1 failed healing.
      The healing status of the repaired meniscus appeared to be related to the
      clinical symptoms. Patients who achieved complete tissue healing had no
      complaint. The healing status exhibited no relationship with age, mechanical
      axis, degree of subluxation, and symptom duration. The mean Lysholm score
      improved from 34.7 preoperatively to 75.6 at follow-up and the mean HSS score
      also significantly increased from 33.5 to 82.2. CONCLUSIONS: We achieved 4
      complete and 8 partial healing (lax or scar) of the medial meniscus in this
      retrospective case series of posterior horn meniscus root repairs performed by 1
      surgeon. Further research is needed to clarify why all patients showed clinical
      improvement despite findings of partial healing on second-look arthroscopy.

PMID- 24944977
TI  - Quadriceps Tendon Rupture due to Postepileptic Convulsion.
AB  - We present a case of quadriceps tendon (QT) rupture. QT ruptures can occur in all
      ages. The cause is mostly traumatic in origin. Spontaneous ruptures that are
      thought to result from predisposing conditions are rare. Post-convulsion QT
      ruptures lacking traumas in their history can be overlooked in clinical
      examinations. This should be born in mind by the attending physician, as early
      diagnosis and treatment of the condition can lead to satisfactory outcomes. 

PMID- 24944978
TI  - Popliteal artery pseudoaneurysm following primary total knee arthroplasty.
AB  - An early diagnosis of popliteal artery pseudoaneurysm-a sequela of popliteal
      artery trauma-is difficult owing to its late presentation following total knee
      arthroplasty. The incidence of a popliteal artery pseudoaneurysm with a hematoma
      presenting only a peripheral nerve injury after total knee arthroplasty is also
      uncommon in the absence of common diagnostic features such as a pulsatile
      swelling with an audible bruit on auscultation. In the present report, we
      describe popliteal artery pseudoaneurysm following total knee arthroplasty. 

PMID- 24944979
TI  - Popliteal artery pseudoaneurysm after anterior cruciate ligament re-revision
      using a rigidfix cross pin.
AB  - Popliteal artery injury is a very rare complication of anterior cruciate ligament
      (ACL) reconstruction. The authors experienced a case of popliteal arterial
      pseudoaneurysm after re-revision of ACL reconstruction using Rigidfix for femoral
      tunnel fixation. Pseudoaneurysm was detected in knee magnetic resonance imaging,
      which caused pain, limit of motion, common peroneal nerve palsy, leg swelling and
      symptoms similar to compartment syndrome. After excision and re-anastomosis of
      the popliteal artery using a greater saphenous vein graft, all symptoms were
      resolved within 3 months except for common peroneal nerve palsy. So we report on
      this case with a review of the literature. 

PMID- 24944980
TI  - What Is Different between Postpolypectomy Fever and Postpolypectomy Coagulation
      Syndrome?

PMID- 24944981
TI  - Endoscopic Ultrasound-Guided Fine Needle Biopsy without Rapid On-Site Cytologic
      Examination: A Time to Change the Paradigm?

PMID- 24944982
TI  - The crucial role of biliary endoscopists in the management of bile leak after
      cholecystectomy.

PMID- 24944983
TI  - Experimental models of pancreatitis.
AB  - Acute pancreatitis is an inflammatory disease characterized by interstitial
      edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its
      severity. Regardless of the extent of tissue injury, acute pancreatitis is a
      completely reversible process with evident normal tissue architecture after
      recovery. Its pathogenic mechanism has been known to be closely related to
      intracellular digestive enzyme activation. In contrast to acute pancreatitis,
      chronic pancreatitis is characterized by irreversible tissue damage such as
      acinar cell atrophy and pancreatic fibrosis that results in exocrine and
      endocrine insufficiency. Recently, many studies of chronic pancreatitis have been
      prompted by the discovery of the pancreatic stellate cell, which has been
      identified and distinguished as the key effector cell of pancreatic fibrosis.
      However, investigations into the pathogenesis and treatment of pancreatitis face
      many obstacles because of its anatomical location and disparate clinical course.
      Due to these difficulties, most of our knowledge on pancreatitis is based on
      research conducted using experimental models of pancreatitis. In this review,
      several experimental models of pancreatitis will be discussed in terms of
      technique, advantages, and limitations. 

PMID- 24944984
TI  - Prevention of postendoscopic retrograde cholangiopancreatography pancreatitis:
      the endoscopic technique.
AB  - Pancreatitis is the most frequent and distressing complication of endoscopic
      retrograde cholangiopancreatography (ERCP). Many recent studies have reported the
      use of pharmacological agents to reduce post-ERCP pancreatitis (PEP); however,
      the most effective agents have not been established. Reduction in the incidence
      of PEP in high-risk patients has been reported through specific cannulation
      techniques such as guide wire-assisted cannulation and the use of pancreatic
      stents. The present review focuses on ERCP techniques for the prevention of PEP. 

PMID- 24944985
TI  - Endoscopic drainage of pseudocysts.
AB  - During the last decade, great progress has been made in minimally invasive
      endoscopic techniques. For pancreatic pseudocysts (PPCs), endoscopic drainage has
      become the first-line therapeutic option. Recent advances in therapeutic
      endoscopic ultrasound (EUS)-related techniques have focused on EUS-guided
      transmural drainage, which is now replacing the conventional endoscopy-guided
      transmural drainage. While transmural drainage is usually performed using
      multiple plastic stents with or without a nasocystic drain, fully covered self
      expandable metal stents are now being used with increasing frequency. In this
      review, we discuss some of the controversies related to the endoscopic drainage
      of PPCs. 

PMID- 24944986
TI  - Endoscopic treatment of pancreatic calculi.
AB  - Chronic pancreatitis is a progressive inflammatory disease that destroys
      pancreatic parenchyma and alters ductal stricture, leading to ductal destruction
      and abdominal pain. Pancreatic duct stones (PDSs) are a common complication of
      chronic pancreatitis that requires treatment to relieve abdominal pain and
      improve pancreas function. Endoscopic therapy, extracorporeal shock wave
      lithotripsy (ESWL), and surgery are treatment modalities of PDSs, although
      lingering controversies have hindered a consensus recommendation. Many
      comparative studies have reported that surgery is the superior treatment because
      of reduced duration and frequency of hospitalization, cost, pain relief, and
      reintervention, while endoscopic therapy is effective and less invasive but
      cannot be used in all patients. Surgery is the treatment of choice when
      endoscopic therapy has failed, malignancy is suspected, or duodenal stricture is
      present. However, in patients with the appropriate indications or at high-risk
      for surgery, endoscopic therapy in combination with ESWL can be considered a
      first-line treatment. We expect that the development of advanced endoscopic
      techniques and equipment will expand the role of endoscopic treatment in PDS
      removal. 

PMID- 24944987
TI  - Postpolypectomy Fever, a rare adverse event of polypectomy: nested case-control
      study.
AB  - BACKGROUND/AIMS: Although postpolypectomy fever (PPF) without colon perforation
      or hemorrhage is rare, its incidence and risk factors have not been investigated.
      The objective of this study was to analyze the incidence and risk factors for PPF
      among inpatients. METHODS: Seven patients with PPF were matched with 70 patients
      without PPF from a total of 3,444 patients who underwent colonoscopic
      polypectomy. The PPF incidence during index hospitalization after colonoscopy was
      calculated, and univariate and multivariate analyses were performed to calculate
      the adjusted odds ratios (ORs) for risk factors. RESULTS: PPF without bleeding or
      perforation in the colon occurred in seven patients (0.2%). The median age was 58
      years for cases and 61 years for controls. The median interval from polypectomy
      to occurrence of fever was 7 hours, and the median duration of fever was 9 hours.
      Polyp size >2 cm (adjusted OR, 1.08; 95% confidence interval [CI], 1.01 to 1.15;
      p=0.02) and hypertension (adjusted OR, 14.40; 95% CI, 1.23 to 180.87; p=0.03)
      were associated with a significantly increased risk of PPF. PPF increased the
      length of hospitalization. CONCLUSIONS: Although the crude incidence of PPF is
      low, PPF may prolong hospitalization. Risk factors for PPF include hypertension
      and large polyps.

PMID- 24944988
TI  - Addition of Endoscopic Ultrasound (EUS)-Guided Fine Needle Aspiration and On-Site
      Cytology to EUS-Guided Fine Needle Biopsy Increases Procedure Time but Not
      Diagnostic Accuracy.
AB  - BACKGROUND/AIMS: Although the diagnostic accuracy of endoscopic ultrasound with
      fine needle aspiration (EUS-FNA) in pancreas adenocarcinoma is high, endoscopic
      ultrasound with fine needle biopsy (EUS-FNB) is often required in other lesions;
      in these cases, it may be possible to forgo initial EUS-FNA and rapid on-site
      cytology evaluation (ROSE). The aim of this study was to compare the diagnostic
      accuracy of EUS-FNB alone (EUS-FNB group) with a conventional sampling algorithm
      of EUS-FNA with ROSE followed by EUS-FNB (EUS-FNA/B group) in nonpancreas
      adenocarcinoma lesions. METHODS: Retrospective cohort study of subjects who
      underwent EUS sampling of nonpancreatic adenocarcinoma lesions between February
      2011 and May 2013. RESULTS: Over the study period, there were 43 lesions biopsied
      in 41 unique patients in the EUS-FNB group and 53 patients in the EUS-FNA/B
      group. Overall diagnostic accuracy was similar between the EUS-FNB and EUS-FNA/B
      groups (83.7% vs. 84.9%; p=1.0). In the subgroup of subepithelial mass lesions,
      diagnostic accuracy remained similar in the EUS-FNB and EUS-FNA/B groups (81.0%
      and 70.6%; p=0.7). EUS-FNB procedures were significantly shorter than those in
      the EUS-FNA/B group (58.4 minutes vs. 73.5 minutes; p<0.0001). CONCLUSIONS: EUS
      FNB without on-site cytology provides a high diagnostic accuracy in nonpancreas
      adenocarcinoma lesions. There appears to be no additive benefit with initial EUS
      FNA but this requires further study in a prospective study.

PMID- 24944989
TI  - Endoscopic management of bile leakage after cholecystectomy: a single-center
      experience for 12 years.
AB  - BACKGROUND/AIMS: Bile leakage is an uncommon but serious complication of
      cholecystectomy. The aim of this study is to evaluate the efficacy of the
      endoscopic management of bile leakage after cholecystectomy. METHODS: A total of
      32 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP),
      because of bile leakage after cholecystectomy, from January 2000 to December 2012
      were reviewed retrospectively. The clinical parameters, types of management, and
      procedure-related complications were documented. RESULTS: Most bile leakages
      presented as percutaneous bile drainage through a Hemovac (68.8%), followed by
      abdominal pain (18.8%). The sites of bile leaks were the cystic duct stump in 25
      patients, intrahepatic ducts in four, liver beds in two, and the common bile duct
      in one. Biliary stenting with or without sphincterotomy was performed in 22 and
      eight patients, respectively. Of the four cases of bile leak combined with bile
      duct stricture, one patient had severe bile duct obstruction and the others had
      mild stricture. Concerning endoscopic modalities, endoscopic therapy for bile
      leak was successful in 30 patients (93.8%). Two patients developed transient post
      ERCP pancreatitis, which was mild, and both recovered without clinical sequelae.
      CONCLUSIONS: The endoscopic approach of ERCP should be considered a primary
      modality for the diagnosis and treatment of bile leakage after cholecystectomy.

PMID- 24944991
TI  - A needle penetrating the stomach cavity after acupuncture.
AB  - Although acupuncture is known as a safe procedure that is widely used in many
      countries, complications including infection, hemorrhage, hematoma, pneumothorax,
      nerve damage, and cardiac tamponade have been reported. A needle penetrating the
      stomach after acupuncture, however, is very rare. Here, we report the case of 47
      year-old woman who experienced abdominal pain 2 days after receiving acupuncture.
      Upper gastrointestinal endoscopy identified an approximately 2.5-cm long needle
      in the posterior wall of the antrum. The needle was removed endoscopically using
      rat tooth forceps with no complications. 

PMID- 24944990
TI  - Intramural gastric abscess caused by a toothpick presenting as a subepithelial
      tumor.
AB  - In the present report, we describe an unusual case of an intramural gastric
      abscess caused by a foreign body, detected in the form of a subepithelial tumor.
      A 64-year-old woman was referred to our gastroenterology clinic for further
      evaluation of a gastric subepithelial tumor. The patient presented with a 1-month
      history of sustained dull epigastric pain. Esophagogastroduodenoscopy revealed an
      ill-demarcated, round, smooth, protruding lesion with a small central erosion on
      the great curvature of the proximal antrum. Endoscopic ultrasonography indicated
      the presence of an ovoid, heterogeneous, hypoechoic lesion with small echogenic
      foci located in the submucosa and muscularis propria layers. An abdominal
      computed tomography scan showed focal gastric wall thickening and regional lymph
      node enlargement. Endoscopic submucosal dissection was performed for definite
      diagnosis and management. Thus, we detected a toothpick and removed it using
      grasping forceps. The final diagnosis was an intramural gastric abscess caused by
      a toothpick. 

PMID- 24944992
TI  - A case of midazolam anaphylaxis.
AB  - Midazolam is a type of anesthetic agent frequently used for conscious sedation
      during a variety of medical procedures. Anaphylactic reactions to midazolam are
      rarely reported. However, we observed a case of midazolam hypersensitivity in
      which emergency measures were required to ensure patient recovery after
      administration of midazolam as a sedative. The occurrence of the anaphylactic
      reaction to midazolam was confirmed by elevated serum tryptase levels. The
      current case report presents a discussion of our findings. 

PMID- 24944993
TI  - Body position adjustment may facilitate capsule endoscopic real-time examination
      in patients with a large amount of food retention in the stomach.
AB  - A patient with acute obscure gastrointestinal bleeding was found to have a large
      amount of food retention in the stomach after fasting for >12 hours. We tried to
      adjust the patient's body position to facilitate capsule endoscopic examination.
      The patient laid on the bed on his right side, which is the position required for
      a normal procedure, and then his hip was raised while his upper body was lowered
      gradually until the pylorus appeared at the center of the screen of the real-time
      monitor. It took 15 minutes of body position adjustment to make the pylorus
      appear at the center of the monitor and another 5 minutes for the capsule
      endoscope to enter the duodenum. The lesion was ultimately found at the terminal
      small intestine. 

PMID- 24944994
TI  - Acute duodenal ischemia and periampullary intramural hematoma after an uneventful
      endoscopic retrograde cholangiopancreatography in a patient with primary
      myelofibrosis.
AB  - Acute duodenal ischemia and periampullary intramural hematoma are rare
      complications after endoscopic retrograde cholangiopancreatography (ERCP). A 77
      year-old man with splenomegaly complained of abdominal pain caused by common bile
      duct (CBD) stone. After successful removal of the CBD stone without immediate
      complications, the patient developed intramural hematoma around the ampulla of
      Vater along with diffuse duodenal edema. The findings were compatible with acute
      intestinal ischemia, and further evaluation revealed that he had underlying
      primary myelofibrosis. Myeloproliferative diseases are known to be significantly
      associated with an increased risk of thrombohemorrhagic complications. Therefore,
      particular attention should be given to this group of patients when a high-risk
      procedure such as ERCP is performed. 

PMID- 24944995
TI  - Fatal Cerebral Air Embolism Due to a Patent Foramen Ovale during Endoscopic
      Retrograde Cholangiopancreatography.
AB  - Fatal air embolism to the cerebrum during an endoscopic retrograde
      cholangiopancreatography (ERCP) has not been reported in a patient with a
      biliodigestive anastomosis and multiresistant extended-spectrum beta-lactamase
      Escherichia coli (ESBL) bacteremia. A 59-year-old woman with a history of
      laparoscopic cholecystectomy and iatrogenic injury of the right choledochal duct,
      choledochojejunostomy (biliodigestive anastomosis), recurrent cholangitis,
      revision of the biliodigestive anastomosis, recurrent liver abscesses, and
      recurrent stenting of stenotic bile ducts, was admitted because of fever and
      tenderness of the right upper quadrant. On ERCP, a previously deployed covered
      Wallstent was replaced. Blood cultures grew ESBL. After stent removal 8 days
      later, the patient did not wake up and developed arterial hypotension and
      respiratory insufficiency, requiring mechanical ventilation. Computed tomography
      scans showed extensive air embolism to the liver, heart, and cerebrum. She died 1
      day later. Although the exact pathogenesis of the fatal cerebral air embolism
      remains speculative, the nonphysiological anatomy and chronic infection with ESBL
      may have been contributory factors. 

PMID- 24944996
TI  - Endoscopic Retrograde Cholangiopancreatography-Related Large Jejunal Perforation:
      Operate or Apply Over-the-Scope Clip Device?

PMID- 24944997
TI  - Recent advances in bioinformatics reveal the molecular heterogeneity of
      hepatocellular carcinoma.

PMID- 24944998
TI  - Molecular biology of liver cancer stem cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers
      worldwide. The concept of cancer stem cells (CSCs) is based primarily on the
      clinical and experimental observations that indicate the existence of a
      subpopulation of cells with the capacity to self-renew and differentiate as well
      as show increased resistance to radiation and chemotherapy. They are considered
      as the factors responsible for the cases of tumor relapse. Hepatic progenitor
      cells (HPCs) could form the basis of some hepatocellular carcinomas (HCC) and
      cholangiocarcinomas. Liver CSCs have been reported in multiple subtypes of HCC
      and are considered as the master regulators of HCC initiation, tumor metastasis,
      and progression. HPCs activators such as epithelial cell adhesion molecule
      (EpCAM), Wnt/beta-catenin, transforming growth factor-beta (TGF-beta), Notch and
      Hedgehog signaling systems expedite tumorigenesis or conversely, serve as a
      powerful cancer-prevention tool. Recent work has also identified Sal-like protein
      4 (SALL4) and some epigenetic regulations as important molecules, while several
      therapeutic drugs that directly control HPCs have been tested both in vivo and in
      vitro. However, liver CSCs clearly have a complex pathogenesis, with the
      potential for considerable crosstalk and redundancy in signaling pathways. Hence,
      the targeting of single molecules or pathways may have limited benefit for
      treatment. In addition to the direct control of liver CSCs, many other factors
      are needed for CSC maintenance including angiogenesis, vasculogenesis, invasion
      and migration, hypoxia, immune evasion, multiple drug resistance, and
      radioresistance. Here, we provide a brief review of molecular signaling in liver
      CSCs and present insights into new therapeutic strategies for their targeting. 

PMID- 24944999
TI  - Hypervascular benign and malignant liver tumors that require differentiation from
      hepatocellular carcinoma: key points of imaging diagnosis.
AB  - Most liver tumors are benign and hypervascular, and it is important to avoid
      unnecessary interventions for benign lesions. This review describes the typical
      and atypical imaging features of common hypervascular benign liver tumors and
      outlines a general approach to distinguishing between benign and malignant
      hepatic lesions. There are many types of benign liver tumors that need to be
      differentiated from hepatocellular carcinoma (HCC). Therefore, it is very
      important to know the imaging characteristics of benign tumors. Gadolinium
      ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance
      imaging is helpful in diagnosing hypervascular pseudotumors, focal nodular
      hyperplasia, and nodular lesions associated with alcohol-induced hepatitis. There
      are also some hypervascular malignant tumors, such as cholangiocarcinoma,
      cholangiolocellular carcinoma, mixed type tumors, and metastatic liver tumors,
      which also required differentiation from HCC. 

PMID- 24945000
TI  - Diagnosis of Pathologically Early HCC with EOB-MRI: Experiences and Current
      Consensus.
AB  - OBJECTIVE: After much debate, the International Consensus Group for
      Hepatocellular Neoplasia (ICGHN) has recently arrived at a conclusion regarding
      the pathological criteria for early hepatocellular carcinoma (HCC). They have
      stated that stromal invasion should be recognized as the most important
      pathological finding for precisely diagnosing and differentiating early HCC from
      dysplastic nodules (DN). METHODS: We conducted a review of the imaging findings
      from multi-imaging modalities of early HCC cases diagnosed according to the
      pathological criteria of the ICGHN. The multi-imaging modalities included
      gadoxetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI),
      abbreviated as EOB-MRI, contrast-enhanced CT (CE-CT), CT during
      arterioportography (CTAP), and CT during hepatic arteriography (CTHA). It has
      been shown that EOB-MRI is the only imaging modality that has sufficient
      resolution for the detection and classification of early HCC. RESULTS: The most
      significant imaging feature for diagnosing early HCC was hypointensity on
      hepatobiliary-phase (HP) images of EOB-MRI; all of the cases of early HCC that
      were detected on HP images of EOB-MRI showed hypointensity, while all of the
      images of DN showed isointensity or hyperintensity compared with the liver
      parenchyma. The results of the diagnostic performance analysis showed that EOB
      MRI had excellent sensitivity (97%) for detecting early HCC and outstanding
      specificity (100%) for distinguishing early HCC from DN. CONCLUSIONS: Considering
      the results from imaging-pathologic correlations and follow-up studies indicating
      that many early-stage hepatocellular nodules showing hypointensity on HP images
      of EOB-MRI tend to develop hypervascularization during a relatively short follow
      up period, it is beginning to be accepted that such nodules may be treated as
      early HCC. However, hepatologists and radiologists should also recognize that
      some cases of early HCC may show isointensity or hyperintensity on HP images of
      EOB-MRI, making it impossible to differentiate early HCC from DN, although the
      low prevalence of such nodules may be unlikely to affect the generally accepted
      follow-up protocols for cirrhotic patients. Our results and other recent reports
      have indicated that signal-intensity patterns on HP images of EOB-MRI for DN and
      early HCC directly correlate with the degree of expression of the organic anion
      transporting polypeptide (OATP) 1B3 in the nodules. Thus, the diagnostic
      performance of pathological analyses for early HCC cases may be dramatically
      improved, nearly up to that of EOB-MRI, by incorporating an OATP1B3 staining
      method.

PMID- 24945002
TI  - How to define transarterial chemoembolization failure or refractoriness: a
      European perspective.
AB  - In Europe, trans-arterial chemoembolization (TACE) is usually given to patients
      with Barcelona Clinic Liver Cancer (BCLC) "intermediate stage" hepatocellular
      carcinoma (HCC), and is associated with a modest improvement in median overall
      survival. In the two positive randomized trials that have been reported, TACE was
      stopped in cases of severe toxicity, worsening of liver cirrhosis or performance
      status and tumor progression, including local progression, extrahepatic spread
      and portal vein thrombosis. The necessity to stop TACE leads to the concept of
      untreatable progression, which is characterized by massive liver involvement,
      extrahepatic spread, vascular invasion, impaired liver function or performance
      status. More recently, the assessment for re-treatment with TACE (ART) score has
      been developed to determine which patients will not benefit from a second or a
      third TACE therapy. Herein, we propose an algorithm that summarizes our
      experience with TACE. 

PMID- 24945001
TI  - Living donor liver transplantation for patients with hepatocellular carcinoma.
AB  - BACKGROUND: Liver transplantation has become an established treatment for
      cirrhotic patients with hepatocellular carcinoma (HCC), and the Milan criteria
      are now widely accepted and applied as an indication for deceased donor liver
      transplantation (DDLT) in Western countries. In contrast, however, due to the
      severe organ shortage, living donor liver transplantation (LDLT) is mainstream in
      Japan and in other Asian countries. SUMMARY: Unlike DDLT, LDLT is not limited by
      the restrictions imposed by the nationwide allocation system, and the indication
      for LDLT in patients with HCC often depends on institutional or case-by-case
      considerations, balancing the burden on the donor, the operative risk, and the
      overall survival benefit for the recipient. Accumulating data from a nationwide
      survey as well as individual center experience indicate that extending the Milan
      criteria is warranted. KEY MESSAGES: While the promotion of DDLT should be
      intensified in Japan and other Asian countries, LDLT will continue to be a
      mainstay for the treatment of HCC in cirrhotic patients.

PMID- 24945003
TI  - Drug therapy for advanced-stage liver cancer.
AB  - Liver cancer was traditionally treated by surgery or interventional ablative
      treatments, or, if these options were not feasible, by best supportive care.
      Since 2008, systemic therapy with the multikinase inhibitor sorafenib has become
      available worldwide and has become the standard of care for unresectable/non
      ablatable or advanced-stage hepatocellular carcinoma (HCC). Sorafenib is able to
      improve the median overall survival by approximately 3 months. Despite this
      significant advance in the non-surgical/non-interventional management of liver
      cancer, this improvement in overall survival is only a first step toward more
      potent, more targeted, and better tolerated oral antitumor treatments. Since the
      introduction of sorafenib into clinical practice, several attempts have been made
      to develop even more effective first-line treatments as well as an effective
      second-line treatment for HCC. None of these endeavors has been successful so
      far. The development of drug treatments for HCC has been particularly hampered by
      the unfortunate push to establish the diagnosis of liver cancer by non-invasive
      imaging alone, without requiring a liver biopsy for histologic confirmation: this
      precluded the very necessary search for informative biomarkers and the search for
      molecular targets for drug development in HCC. This important drawback is being
      increasingly recognized and corrected. Despite several obstacles remaining to be
      overcome, it seems reasonable to assume that using a rational, data-driven
      approach, we will be able to develop better drug treatments for liver cancer in
      the coming years. 

PMID- 24945006
TI  - Concurrent stenoses: A common etiology of stroke in Asians.
AB  - Atherosclerosis of cerebral vessels is a common cause of stroke. Racial
      differences in the distribution of cerebrovascular occlusive disease are well
      documented. Extracranial stenosis is more common in Caucasians, while
      intracranial stenosis is more common in Asians, Hispanics and African-Americans.
      Concurrent atherosclerosis of extracranial and intracranial vessels is common in
      Asians. The incidence of concurrent stenoses ranges from 10% to 48% in patients
      with symptomatic cerebrovascular disease. The long-term prognosis of these
      patients is poor and they are at high risk of further vascular events or death.
      The purpose of this review is to examine the epidemiology, risk factors, stroke
      mechanism and genetics of concurrent stenoses and to discuss strategies for
      treatment. 

PMID- 24945007
TI  - Case of early right ventricular pacing lead perforation and review of the
      literature.
AB  - We report a case of a 77-year-old patient with complete atrioventricular block.
      She underwent permanent pacemaker implantation complicated by right ventricular
      lead perforation. This was suspected on transthoracic echocardiogram and
      confirmed by chest computed tomography. The lead was repositioned in the cardiac
      electrophysiology lab followed by an uneventful course thereafter. 

PMID- 24945005
TI  - Therapeutic strategies for targeting the ovarian tumor stroma.
AB  - Epithelial ovarian cancer is the most lethal type of gynecologic malignancy.
      Sixty percent of women who are diagnosed with ovarian cancer present with
      advanced-stage disease that involves the peritoneal cavity and these patients
      have a 5-year survival rate of less than 30%. For more than two decades, tumor
      debulking surgery followed by platinum-taxane combination chemotherapy has
      remained the conventional first-line treatment of ovarian cancer. Although the
      initial response rate is 70%-80%, most patients with advanced-stage ovarian
      cancer eventually relapse and succumb to recurrent chemoresistant disease. A
      number of molecular aberrations that drive tumor progression have been identified
      in ovarian cancer cells and intensive efforts have focused on developing
      therapeutic agents that target these aberrations. However, increasing evidence
      indicates that reciprocal interactions between tumor cells and various types of
      stromal cells also play important roles in driving ovarian tumor progression and
      that these stromal cells represent attractive therapeutic targets. Unlike tumor
      cells, stromal cells within the tumor microenvironment are in general genetically
      stable and are therefore less likely to become resistant to therapy. This concise
      review discusses the biological significance of the cross-talk between ovarian
      cancer cells and three major types of stromal cells (endothelial cells,
      fibroblasts, macrophages) and the development of new-generation therapies that
      target the ovarian tumor microenvironment. 

PMID- 24945008
TI  - Perforated jejunal ulcer associated with gastric mucosa in a jejunal
      diverticulum.
AB  - Jejunal diverticula are rare and subsequent complications even more so. The usual
      small bowel diverticulum encountered by general surgeons is a Meckel's. These are
      embryological remnants of the vitello-intestinal duct and are on the anti
      mesenteric surface of the terminal ileum. They may contain heterotopic gastric or
      pancreatic mucosa. Herein we explore the case of a young girl who presented with
      features of peritonitis secondary to a complication from a jejunal diverticulum.
      The case, pathology, complications and treatment of jejunal diverticulosis and
      heterotopic gastric mucosa in the jejunum are explored. 

PMID- 24945009
TI  - Abnormal electrocardiogram in a patient with amyotrophic lateral sclerosis
      mimicking myocardial ischaemia.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      that almost exclusively involves motor neurons although autonomic dysfunction has
      also been reported. We present an 84-year-old female with no documented history
      of heart disease, who was admitted with negative T waves in the electrocardiogram
      precordial leads mimicking myocardial ischaemia. No other abnormalities were
      shown in the rest of the cardiologic evaluation, suggesting autonomic nervous
      system dysfunction. A neurophysiological study demonstrated acute and chronic
      denervation in multiple muscles with normal nerve conduction studies, confirming
      ALS diagnosis. Previous studies have shown that subclinical sympathetic
      hyperfunction and parasympathetic hypofunction might result in cardiovascular
      dysfunction in ALS patients. It is important to detect disturbances of autonomic
      cardiac control because this dysfunction may influence survival and quality of
      life, leading to a decrease in life expectancy in ALS patients. This Case Report
      may support the impairment of cardiac autonomic control in patients with ALS. 

PMID- 24945010
TI  - Pyonephrosis as a sign of sarcomatoid carcinoma of the renal pelvis.
AB  - We report the case of an urgent nephrectomy because of a pyonephrosis and sepsis
      due to an unsuspected sarcomatoid transitional cell carcinoma, an infrequent
      subtype with a bad oncological prognosis. We present a 58-year-old man assessed
      by internal medicine for a general syndrome and weakness many months previously.
      A pyonephrotic kidney was observed at abdominal computed tomography in the
      context of septic shock, without suspecting the underlying cause. The pathology
      report described a sarcomatoid transitional cell carcinoma. Sarcomatoid
      transitional cell carcinoma is an invasive and infrequent subtype of urothelial
      tumors. The symptoms are often the same as other renal masses; however, in this
      case, sepsis and pyonephrosis were the rare initial symptoms. 

PMID- 24945011
TI  - Two-level reconstruction of isolated fracture of the lesser tuberosity of the
      humerus.
AB  - Fractures of the lesser tuberosity of the humerus are typically met in
      combination with other injuries of the shoulder. Case reports of isolated lesser
      tuberosity fractures are particularly rare and, consequently, therapeutic
      protocols have not yet been completely clarified. Conservative as well as
      surgical treatment has been recommended, while several operative techniques have
      been applied. We present a case of a 39-year-old man with an isolated lesser
      tuberosity fracture who was treated surgically in our institution. Due to
      fracture comminution, a two-level reconstruction technique with headless screws
      and buttress plate was applied. As far as we know, this method of fixation of
      this type of fracture has not been previously described in the literature. The
      patient tolerated the procedure well and excellent results were obtained at the
      latest follow-up. 

PMID- 24945004
TI  - Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review.
AB  - Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of
      oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in
      relation to the management of head and neck squamous cell carcinoma have been
      changing. Research into HPV-related oropharyngeal squamous cell carcinoma is
      rapidly expanding, however many molecular pathological and clinical aspects of
      the role of HPV remain uncertain and are the subject of ongoing investigation. A
      detailed search of the literature pertaining to HPV-related oropharyngeal
      squamous cell carcinoma was performed and information on the topic was gathered.
      In this article, we present an extensive review of the current literature on the
      role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to
      epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications.
      HPV has been established as a causative agent in oropharyngeal squamous cell
      carcinoma and biologically active HPV can act as a prognosticator with better
      overall survival than HPV-negative tumours. A distinct group of younger patients
      with limited tobacco and alcohol exposure have emerged as characteristic of this
      HPV-related subset of squamous cell carcinoma of the head and neck. However, the
      exact molecular mechanisms of carcinogenesis are not completely understood and
      further studies are needed to assist development of optimal prevention and
      treatment modalities. 

PMID- 24945012
TI  - Simultaneous bilateral robotic partial nephrectomy: Case report and critical
      evaluation of the technique.
AB  - We report our first simultaneous bilateral robot assisted partial nephrectomy
      (RAPN) in order to show and critically discuss the feasibility of this procedure.
      Materials and methods A 69-year-old male patient visited our department due to
      incidental finding of bilateral mesorenal small masses (2.5 cm on the right and
      3.5 cm on the left) suspicious for malignancy. We started from the right side
      with patient in flank position. Port placement: 12-mm periumbilical camera port,
      two 8-mm robotic ports in wide ''V''configuration, additional 12 mm assistant
      port on the midline between the umbilicus and symphysis pubis. A right unclamping
      RAPN with sliding clip renorrhaphy was performed. The trocars were removed and
      the robot undocked. Without interrupting the anesthesiological procedures, the
      patient was reported in supine position and, after 180 degrees rotation of the
      surgical bed, was newly placed in contralateral flank position. Using both the
      previous periumbilical and midline ports, two other 8-mm robotic trocars were
      placed. The robot was then redocked and RAPN was also performed on the left side
      using the same previously reported technique. Results Total time: 285 min.
      Estimated blood losses: 150 cc. Postoperative period: uneventful. Pathological
      examination: bilateral renal cell carcinoma, negative surgical margins.
      Conclusions Our experience was encouraging and confirmed the feasibility and
      safety of this procedure. The planning of our technique was time and cost
      effective with cosmetic benefit for the patient. However, we think that an
      appropriate selection of the patients and a skill in robotic renal surgery are
      advisable before approaching this type of surgery. 

PMID- 24945013
TI  - Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case
      reports.
AB  - Prostate cancer is the most common non-cutaneous malignancy for men. The skeleton
      is the most common metastatic site but, following an improvement in survival,
      metastases in uncommon sites are being found more frequently in clinical
      practice, especially brain metastases. Despite the new drugs now available for
      metastatic castration resistant prostate cancer, no clinical evidence exists
      about their effectiveness on brain metastases. We describe the clinical history
      of 3 patients treated with cabazitaxel plus whole brain radiotherapy. These case
      reports demonstrate that cabazitaxel is highly active and well tolerated in brain
      metastases. 

PMID- 24945014
TI  - Gastrointestinal perforation due to incarcerated Meckel's diverticulum in right
      femoral canal.
AB  - Meckel's diverticulum is a very common congenital anomaly of the gastrointestinal
      tract but many cases remain asymptomatic and are diagnosed incidentally during
      laparoscopic or other surgical procedures. Cases of femoral hernia involving
      Meckel's diverticulum are rare, with less than 50 cases reported in the
      literature since Littre published the first description of this coincident
      condition over 300 years ago. While all true "Littre's hernias" contain a
      Meckel's diverticulum, the involved anatomical sites are various, the most common
      being the inner groin (inguinal), the outer groin (femoral), and the belly button
      (umbilical). Complications of Littre's hernias include incarceration,
      strangulation, necrosis, and perforation. Herein, we describe a case of Littre's
      hernia that involved an incarcerated Meckel's diverticulum in a femoral hernia
      that was diagnosed upon investigation of symptomology manifesting from
      perforation and was successfully managed by surgical resection with stapler
      devices. 

PMID- 24945015
TI  - Facial nerve palsy, headache, peripheral neuropathy and Kaposi's sarcoma in an
      elderly man.
AB  - We present a case of an elderly man, who initially presented with right facial
      nerve palsy, ipsilateral headache, elevated erythrocyte sedimentation rate (ESR)
      and no fever. A presumptive diagnosis of giant cell arteritis was made and the
      patient was treated with high-dose steroids. A temporal artery biopsy was
      negative. Several months later, while on 16 mg of methylprednisolone daily, he
      presented with severe sensorimotor peripheral symmetric neuropathy, muscle
      wasting and inability to walk, uncontrolled blood sugar and psychosis. A work-up
      for malignancy was initiated with the suspicion of a paraneoplastic process. At
      the same time a biopsy of the macular skin lesions that had appeared on the skin
      of the left elbow and right knee almost simultaneously was inconclusive, whereas
      a repeat biopsy from the same area of the lesions that had become nodular, a
      month later, was indicative of Kaposi's sarcoma. Finally, a third biopsy of a
      similar lesion, after spreading of the skin process, confirmed the diagnosis of
      Kaposi's sarcoma. He was treated with interferon alpha and later was seen in very
      satisfactory condition, with no clinical evidence of neuropathy, normal muscle
      strength, no headache, normal electrophysiologic nerve studies, involution of
      Kaposi's lesions and a normal ESR. 

PMID- 24945016
TI  - Right hemisphere dysfunction is better predicted by emotional prosody impairments
      as compared to neglect.
AB  - BACKGROUND: Neurologists generally consider hemispatial neglect to be the primary
      cognitive deficit following right hemisphere lesions. However, the right
      hemisphere has a critical role in many cognitive, communication and social
      functions; for example, in processing emotional prosody (tone of voice). We
      tested the hypothesis that impaired recognition of emotional prosody is a more
      accurate indicator of right hemisphere dysfunction than is neglect. METHODS: We
      tested 28 right hemisphere stroke (RHS) patients and 24 hospitalized age and
      education matched controls with MRI, prosody testing and a hemispatial neglect
      battery. Emotion categorization tasks assessed recognition of emotions from
      prosodic cues. Receiver operating characteristic (ROC) analyses were used to
      compare tests in their ability to distinguish stroke patients from controls.
      RESULTS: ROC analyses revealed that the Prosody Score was more effective than the
      Neglect Battery Score in distinguishing stroke patients from controls, as
      measured by area under the curve (AUC); Prosody Score = 0.84; Neglect Battery
      Score =0. 57. The Prosody Score correctly classified 78.9%, while Neglect Score
      correctly classified 55.8% of participants as patients versus controls. The
      Prosody Score was similar to the total NIH Stroke Scale in identifying RHS
      patients (AUC=0.86, correctly classifying 80.1% of patients versus controls), but
      the tests only partially overlapped in the patients identified. CONCLUSIONS:
      Severe prosody impairment may be a better indicator of right hemisphere
      dysfunction than neglect. Larger studies are needed to determine if including a
      bedside test of Prosody with the NIH Stroke Scale would most efficiently and
      reliably identify right hemisphere ischemia.

PMID- 24945017
TI  - The Specificity of Adaptation to Real-Time Formant Shifting.
AB  - In this study, two experiments were conducted to investigate the specificity of
      adaptation to real-time formant shifting. During the experiments, talkers were
      adapted to altered auditory feedback for one vowel (trained vowel) and received
      unaltered feedback for a different vowel (untrained vowel). In the first
      experiment, production of the untrained vowel was measured while the talker was
      in the process of adapting to the altered feedback for the trained vowel. In the
      second experiment, production of the untrained vowel was measured after talkers
      had adapted to the altered feedback for the trained vowel. In both experiments,
      talkers spontaneously modified production of the trained vowel in response to the
      altered auditory feedback. In the first experiment, talkers slightly altered
      production of the untrained vowel while the trained vowel was adapting to the
      altered feedback. In the second experiment, production of the untrained vowel was
      not altered after talkers had completely adapted to the altered feedback of the
      trained vowel. These results suggest that the degree of generalization depends on
      the conditions of adaptation and on the information available about the acoustic
      environment.

PMID- 24945018
TI  - [War is also a Public Health problem].

PMID- 24945019
TI  - [A call for communicating knowledge from professional practice].

PMID- 24945020
TI  - [Program of field applied epidemiology].

PMID- 24945021
TI  - [Health and information for the 21st century: WHO bets on the Internet].

PMID- 24945022
TI  - [Vitamin and mineral supplement consumption in the adult healthy population from
      5 Spanish provinces].

PMID- 24945023
TI  - Radiographic anatomy and barium sulfate contrast transit time of the
      gastrointestinal tract of bearded dragons (Pogona vitticeps).
AB  - The positive contrast gastrointestinal study is a common non-invasive diagnostic
      technique that does not require anesthesia and enables good visualization of the
      digestive tract. Radiographic anatomy and reference intervals for
      gastrointestinal contrast transit time in inland bearded dragons (Pogona
      vitticeps) were established using seven animals administered 15 ml/kg of a 35%
      w/v suspension of barium by esophageal gavage. Dorso-ventral and lateral
      radiographic views were performed at 0, 15, 30 min, 1, 2, 4, 6, 8, 12 h, and then
      every 12 h up to 96 h after barium administration. Gastric emptying was complete
      at a median time of 10 h (range 4-24 h). Median jejunum and small intestinal
      emptying times were 1 h (range 30 min-2 h) and 29 h (range 24-48 h),
      respectively. Median transit time for cecum was 10 h (range 8-12 h). Median time
      for contrast to reach the colon was 31 h (range 12-72 h) after administration.
      Results were compared to those obtained in other reptilian species. This
      technique appeared safe in fasted bearded dragons and would be clinically
      applicable in other lizard species.

PMID- 24945024
TI  - Effects of gadoxetate disodium (Eovist((r))) contrast on magnetic resonance
      imaging characteristics of the liver in clinically healthy dogs.
AB  - Gadoxetate disodium (Gd-EOB-DTPA; gadolinium-ethoxybenzyl-diethylene triamine
      penta-acetic acid) is a newly developed paramagnetic contrast agent reported to
      have a high specificity for the hepatobiliary system in humans. The purpose of
      this prospective study was to describe effects of Gd-EOB-DTPA contrast
      administration on MRI characteristics of the liver in eight clinically healthy
      dogs. Precontrast dorsal and transverse T1-weighted spin echo, T2-weighted fast
      spin echo, and transverse T1-weighted 3D gradient echo (VIBE; volume-interpolated
      body examination) pulse sequences were acquired for each dog. Dogs were assigned
      to four groups based on contrast dose administered (0.0125 mmol/kg or 0.025
      mmol/kg), and pulse sequences acquired after contrast administration (T1-weighted
      spin echo and T1-weighted 3D gradient echo). Liver signal intensity ratios were
      calculated and compared between the two contrast dose groups and two postcontrast
      pulse sequence groups using ANOVA. No adverse effects of contrast administration
      were observed. All dogs exhibited homogeneous contrast enhancement of the liver
      with no statistical difference in enhancement between the two different contrast
      doses. Contrast enhancement in all dogs peaked between 1 and 10 min after
      intravenous injection. There was a significant difference in mean signal
      intensity ratios between sequences (P = 0.035) but not between doses (P = 0.421).
      Postcontrast signal intensities of the liver parenchyma were significantly higher
      for the T1-weighted 3D gradient echo images when compared to the T1-weighted spin
      echo sequences. Findings indicated that Gd-EOB-DTPA contrast administration is
      safe in healthy dogs and causes homogeneous enhancement of the liver that is more
      pronounced in T1-weighted 3D gradient echo MRI pulse sequences.

PMID- 24945025
TI  - [Ignacio Chavez Rivera, 1928-2012].

PMID- 24945026
TI  - [New developments in radiation therapy].

PMID- 24945027
TI  - Reply: To PMID 23588603.

PMID- 24945028
TI  - Petar Alaupovic: The father of lipoprotein classification based on apolipoprotein
      composition.

PMID- 24945029
TI  - [What is the purpose and the target of GIN: who has doubts?].

PMID- 24945030
TI  - [Assessment of right ventricular function in patients with chronic kidney disease
      stage IV NKF].
AB  - Cardiovascular diseases are accountable for almost 50% of over-all mortality
      rates in chronic kidney disease (CKD) patients, especially in those who undergo
      hemo-dialysis or peritoneal dialysis.Hemodialysis patients present higher rates
      of pulmonary hypertension (PH), an independent risk factor for cardiovascular
      mortality among this patient population, due in part to the presence and
      hemodynamic effects of vascular access (both artero-venous fistula and central
      venous catheter). Echocardiographic TAPSE (tricuspid annular plane systolic
      excursion) index represents a helpful tool for investigation of right ventricular
      function together with PAPs (systolic pulmonary artery pressure) evaluation.The
      following study protocol, introduced by the Cardionephrology Study Group of the
      Italian Society of Nephrology, aims to evaluate the incidence of right
      ventricular dysfunction and PH in CKD patients. This is a multicentric, case-
      control study which includes two arms, each comprising 200 patients, and which
      will last 24-36 months.Glomerular filtration rates (GFR) are calculated using the
      eGFR EPI equation, while echocardiographic evaluation includes atrial and
      ventricular dimension and area, left ventricular systolic function (ejection
      fraction), diastolic function, TAPSE index measurement and PAPs evaluation.

PMID- 24945031
TI  - Importance of baseline specification in evaluating conservation interventions and
      achieving no net loss of biodiversity.
AB  - There is an urgent need to improve the evaluation of conservation interventions.
      This requires specifying an objective and a frame of reference from which to
      measure performance. Reference frames can be baselines (i.e., known biodiversity
      at a fixed point in history) or counterfactuals (i.e., a scenario that would have
      occurred without the intervention). Biodiversity offsets are interventions with
      the objective of no net loss of biodiversity (NNL). We used biodiversity offsets
      to analyze the effects of the choice of reference frame on whether interventions
      met stated objectives. We developed 2 models to investigate the implications of
      setting different frames of reference in regions subject to various biodiversity
      trends and anthropogenic impacts. First, a general analytic model evaluated
      offsets against a range of baseline and counterfactual specifications. Second, a
      simulation model then replicated these results with a complex real world case
      study: native grassland offsets in Melbourne, Australia. Both models showed that
      achieving NNL depended upon the interaction between reference frame and
      background biodiversity trends. With a baseline, offsets were less likely to
      achieve NNL where biodiversity was decreasing than where biodiversity was stable
      or increasing. With a no-development counterfactual, however, NNL was achievable
      only where biodiversity was declining. Otherwise, preventing development was
      better for biodiversity. Uncertainty about compliance was a stronger determinant
      of success than uncertainty in underlying biodiversity trends. When only
      development and offset locations were considered, offsets sometimes resulted in
      NNL, but not across an entire region. Choice of reference frame determined
      feasibility and effort required to attain objectives when designing and
      evaluating biodiversity offset schemes. We argue the choice is thus of
      fundamental importance for conservation policy. Our results shed light on
      situations in which biodiversity offsets may be an inappropriate policy
      instrument.

PMID- 24945032
TI  - Moving Rio forward and avoiding 10 more years with little evidence for effective
      conservation policy.

PMID- 24945033
TI  - Low-dose aspirin in primary prevention revisited.

PMID- 24945034
TI  - Primary prevention of stroke in women.

PMID- 24945036
TI  - Use of complementary and traditional medicine in the menopause.

PMID- 24945035
TI  - Safety of low-dose paroxetine.

PMID- 24945037
TI  - Impact of obstructive sleep apnea on cardiovascular outcomes in patients treated
      with percutaneous coronary intervention: rationale and design of the sleep and
      stent study.
AB  - Elucidating the effects of obstructive sleep apnea (OSA) on cardiovascular
      outcomes is crucial in risk assessments and therapeutic recommendations for
      affected individuals. The Sleep and Stent Study is a multicenter observational
      study investigating the relationships between OSA and cardiovascular outcomes in
      patients treated with percutaneous coronary intervention (PCI). Eight centers in
      5 countries (Singapore, China and Hong Kong, India, Myanmar, and Brazil) are
      participating in the study, and the recruitment target is 1600 patients. Adult
      patients age 18 to 80 years who have undergone successful PCI are eligible.
      Recruited patients will undergo an overnight sleep study using a level-3 portable
      diagnostic device before hospital discharge. The sleep tracings will be analyzed
      by a certified sleep technologist and audited by a sleep physician, both of whom
      will be blinded to other study data. The patients will be divided into 2 groups
      based on apnea-hypopnea index (AHI): OSA (AHI >=15) and non-OSA (AHI <15) groups.
      The primary study endpoint of cardiovascular death, myocardial infarction,
      stroke, and unplanned revascularization will be compared between the OSA and non
      OSA groups at a median follow-up of 2 years. Secondary endpoints include all
      cause mortality, target-vessel revascularization, stent thrombosis, and
      hospitalization for heart failure. As of December 31, 2013, a total of 1358
      patients have been recruited. Based on the complete preliminary results of the
      first 785 recruited patients, the prevalence of OSA was 48.3%. We expect the
      follow-up for primary endpoint to be completed in late 2015; study results will
      be presented in 2016.

PMID- 24945038
TI  - A reevaluation of the costs of heart failure and its implications for allocation
      of health resources in the United States.
AB  - The annual cost of heart failure (HF) is estimated at $39.2 billion. This has
      been acknowledged to underestimate the true costs for care. The objective of this
      analysis is to more accurately assess these costs. Publicly available data
      sources were used. Cost calculations incorporated relevant factors such as
      Medicare hospital cost-to-charge ratios, reimbursement from both government and
      private insurance, and out-of-pocket expenditures. A recently published
      Atherosclerosis Risk in Communities (ARIC) HF scheme was used to adjust the HF
      classification scheme. Costs were calculated with HF as the primary diagnosis (HF
      in isolation, or HFI) or HF as one of the diagnoses/part of a disease milieu (HF
      syndrome, or HFS). Total direct costs for HF were calculated at $60.2 billion
      (HFI) and $115.4 billion (HFS). Indirect costs were $10.6 billion for both. Costs
      attributable to HF may represent a much larger burden to US health care than what
      is commonly referenced. These revised and increased costs have implications for
      policy makers.

PMID- 24945039
TI  - Health in the Arab world.
AB  - Ischaemic heart disease overtook lower respiratory infections as the leading
      cause of death in 2010.

PMID- 24945040
TI  - Guidelines for a successful European Society  of Cardiology grant application.
AB  - There is no certain way of obtaining one of the European Society of Cardiology
      grants for research or clinical training offered each year, but Prof. Stavros
      Konstantinides (Centre for Thrombosis and Haemostasis, Johannes Gutenberg
      University, Mainz, Germany), who chairs the European Society of Cardiology
      Credentials Committee, which makes proposals to the ESC Board, has helped Barry
      Shurlock PhD to sketch a scenario that contains many useful hints.

PMID- 24945041
TI  - Tako-Tsubo cardiomyopathy.
AB  - Mansencal Nicolas discussed the latest evidence at the International Conference
      on Heart and Brain.

PMID- 24945042
TI  - Does aetiology matter in secondary prevention  of stroke?
AB  - Two experts present the arguments for and against the importance of aetiology in
      secondary prevention of stroke.

PMID- 24945043
TI  - [Change the country so that we don't have to change country].

PMID- 24945044
TI  - [The Academy of Ideas - second edition 2014].
AB  - The Academy of Ideas is an initiative of the Italian Society of Nephrology,
      dedicated to young people who work in nephrology. The 2014 edition wants to
      foster innovative ideas at different levels of maturity along the research and
      innovation process, through two distinct sections meant for people who present
      basic or applied research ideas and for people who submit proofs of concepts
      transferable to products or services in a relatively short time period. The
      proposal aims to enhance grant application skills, giving to young researchers
      the opportunity of collaborating with multi-disciplinary groups of professionals;
      help young researchers to exploit ideas arising from clinical research and
      showing a Technology Readiness Level that allows immediate or close in time
      applicability; foster the understanding of the business perspective in the
      nephrology sector: giving to young scientists the opportunity to have in-hand
      experience on challenges related to bringing to the market research results;
      create a network of knowledge and collaboration among young researchers to
      facilitate the establishment of collaborative relationships and promote the
      creation of new projects and publications of high scientific impact.

PMID- 24945045
TI  - Functional foods.

PMID- 24945046
TI  - International nurses' day. Child health centre.

PMID- 24945047
TI  - Pregnancy and return to work discrimination.

PMID- 24945048
TI  - New global panel to promote nursing leaders.

PMID- 24945049
TI  - Palliative care.

PMID- 24945050
TI  - Making palliative care everyone's business.

PMID- 24945051
TI  - No jobs.

PMID- 24945052
TI  - [Progress in insertion sites for foreign sequence of foot and mouth disease
      virus].
AB  - With the progess in studying gene structure and function of foot and mouth
      disease virus (FMDV), FMDV can express exogenous genes in different sites.
      Through transforming and modifying FMDV can achieve different application
      purposes such as improving virus titer, introducing tag, improving immune
      responses, and reducing pathogenicity. From the perspective of FMDV receiving
      inserted exogenous gene, this paper mainly describes the latest relevant
      developments of FMDV's expression to exogenous gene.

PMID- 24945053
TI  - [Effect of precursor on growth and accumulation of alkaloids of Lycoris radiata
      suspension cells].
AB  - In order to investigate the effects of phenylalanine, tyrosine and tyramine on
      the growth of Lycoris radiata suspension cells and the accumulation of alkaloids,
      the growth quantity of the cells as well as the content of alkaloids in cells
      were determined, which were treated with above three kinds of precursors alone
      and phenylalanine combined with tyrosine respectively. The results indicate that
      the addition of phenylalanine alone and addition of phenylalanine on the basis of
      tyrosine at high concentration (200 micromol/L) had no significant effect on the
      growth of Lycoris radiata suspension cells and the content of alkaloids in cells;
      whereas tyrosine and tyramine promoted the growth of the cells and alkaloids
      accumulation. Treated with tyrosine at high concentration (200 micromol/L), the
      content of alkaloids of the cells was 2.56-fold higher than that of the control
      group, the amounts of lycoramine (3.77 mg/g) and galanthamine (4.46 mg/g) were
      6.61-fold and 6.97-fold higher than that of the control group, respectively. When
      treated with tyramine (200 micromol/L), the amount of alkaloids in Lycoris
      radiata suspension cells was 2.63-fold higher than that of the control group, and
      the amounts of lycoramine (4.45 mg/g) and galanthamine (5.14 mg/g) were 9.08-fold
      and 9.18-fold higher than that of the control group, respectively. The above
      results demonstrate that adding tyrosine and tyramine in the media significantly
      promoted the growth of the Lycoris radiata suspension cells and alkaloids
      accumulation in the cells.

PMID- 24945058
TI  - Method for modeling driving cycles, fuel use, and emissions for over snow
      vehicles.
AB  - As input to a winter use plan, activity, fuel use, and tailpipe exhaust emissions
      of over snow vehicles (OSV), including five snow coaches and one snowmobile, were
      measured on a designated route in Yellowstone National Park (YNP). Engine load
      was quantified in terms of vehicle specific power (VSP), which is a function of
      speed, acceleration, and road grade. Compared to highway vehicles, VSP for OSVs
      is more sensitive to rolling resistance and less sensitive to aerodynamic drag.
      Fuel use rates increased linearly (R2>0.96) with VSP. For gasoline-fueled OSVs,
      fuel-based emission rates of carbon monoxide (CO) and nitrogen oxides (NOx)
      typically increased with increasing fuel use rate, with some cases of very high
      CO emissions. For the diesel OSVs, which had selective catalytic reduction and
      diesel particulate filters, fuel-based NOx and particulate matter (PM) emission
      rates were not sensitive to fuel flow rate, and the emission controls were
      effective. Inter vehicle variability in cycle average fuel use and emissions
      rates for CO and NOx was substantial. However, there was relatively little inter
      cycle variation in cycle average fuel use and emission rates when comparing
      driving cycles. Recommendations are made regarding how real-world OSV activity,
      fuel use, and emissions data can be improved.

PMID- 24945059
TI  - Editorial.

PMID- 24945061
TI  - Overcoming challenges in the management of schizophrenia.
AB  - The authors discuss the impact of the recently available 'atypical' antipsychotic
      drugs on the management of people with schizophrenia. The better tolerability of
      the atypical agents, compared with conventional antipsychotics, should encourage
      their use as first-line therapy and therefore increase the acceptability of early
      intervention strategies. Tailoring treatment to the individual by appropriate
      selection of an atypical agent should facilitate the establishment of a
      productive, long-term therapeutic alliance and could achieve greater concordance
      between doctors and patients. Atypical antipsychotic drugs enable an improvement
      in management strategies which should contribute to a better outcome for patients
      with schizophrenia. 

PMID- 24945060
TI  - The economic value of atypical antipsychotics: A comparison of risperidone and
      olanzapine revisited.
AB  - Careful analysis of clinical experience to date throws fresh light on the optimal
      and actual doses used in clinical practice of risperidone and olanzapine. Since
      launch, the optimal dose for treatment of schizophrenia of risperidone has been
      established at 4-6 mg/day and that of olanzapine at around 15 mg/day. We have
      applied these more realistic dosing assumptions to the published economic
      comparisons between the various atypical agents and conclude that there are
      economic and efficacy arguments for risperidone to be considered as the first
      choice for treatment of patients with schizophrenia. The other atypicals, such as
      olanzapine and clozapine, should be used as second-line therapy in preference to
      conventional agents such as haloperidol. Funding arguments support this approach
      and reinforce the need to reconsider therapy for patients whose current treatment
      may not be optimal. 

PMID- 24945062
TI  - Recent advances in antidepressant drug therapy.
AB  - Many new antidepressants are available for use. The acute effects of
      administration are mainly manifested as side-effects, whereas the chronic effects
      take 2-3 weeks to set in and are responsible for therapeutic action. Such changes
      may include formation and release of neurotransmitters, changes in pre-synaptic
      uptake, and changes in receptor density and sensitivity. The noradrenergic and
      serotonergic systems are not separate, but are entwined with each other. The
      newer SSRI citalopram, and drugs from the SNRI, NaSSA and NAN classes, have been
      shown in controlled trials to be equivalent to, or more efficacious than, TCAs
      and/or SSRIs. They have an improved side-effect profile, especially when compared
      to TCAs, and hence are better tolerated. 

PMID- 24945063
TI  - Fluoxetine and dothiepin therapy in primary care and health resource utilization:
      Evidence from the United Kingdom.
AB  - We attempted to evaluate differences in healthcare resource utilization following
      the initiation of antidepressant therapy with dothiepin or fluoxetine in primary
      care in the United Kingdom, by means of retrospective analysis of data from the
      Doctors Independent Network (DIN-LINK) records system, with a two-stage, multiple
      regression adjusted for potential bias stemming from non-random selection of
      initial drug choice in clinical practice. We counted patients' use of healthcare
      resources in the year following initiation of antidepressant therapy. After
      controlling for both observed and unobserved baseline characteristics correlated
      with initial drug selection, we found that dothiepin patients would have 0.18
      additional non-accident and emergency (ACE) admission, 0.007 more ACE admissions,
      and 1.09 more general referrals than patients who started therapy with
      fluoxetine. Fluoxetine patients would have 0.35 more prescriptions for the
      initial antidepressant. Dothiepin patients would make 5.4 fewer visits to GPs'
      surgery, have 0.2 fewer prescriptions for hypnotic drugs, and 6.5 fewer
      prescriptions for other drugs than fluoxetine patients. This shows that the total
      economic impact of initial antidepressant selection is broader than the
      acquisition costs of antidepressants. 

PMID- 24945064
TI  - Neuropsychiatric assessment as a secondary outcome measure in a multiple
      sclerosis intravenous immunoglobulin L(IMg) trial.
AB  - Multiple sclerosis (MS) patients often suffer from abnormalities of mood
      including euphoria, depression, anxiety, pathological laughing and crying (PLC),
      and psychoses. We assessed neuropsychological functions (NF) as secondary outcome
      measures in relapsing-remitting multiple sclerosis (RRMS) patients treated by
      intravenous immunoglobulin (IVIg). Forty RR-MS patients (mean age 34.5+/-2.4; M :
      F=8: 32) were randomized to receive either IVIg or placebo in a double-blind
      trial for 2 years. NF evaluation at baseline, 1 and 2 years included the Goldberg
      Anxiety and Depression scales, the Brief Psychiatric Rating Scale, the Hamilton
      Anxiety Scale, the Beck Depression Inventory, and the Mini-Mental State
      Examination. Baseline anxiety, depression and general psychopathology scores were
      similar for the IVIg and placebo groups. At 1 and 2 years, anxiety, depression
      and general psychopathology had decreased similarly in both groups compared with
      baseline. No significant cognitive changes were observed in either group. In the
      IVIg group PLC emerged in one patient and one patient developed clinically overt
      depression necessitating antidepressant treatment. In the placebo group, two
      patients developed a hypomanic episode, and PLC emerged in two patients. IVIg
      treatment is safe, according to psychiatric outcome measures, and these measures
      should be routinely used in RR-MS drug trials. 

PMID- 24945065
TI  - Perceived quality of life in depression: Effect of clinical and demographic
      variables.
AB  - The objective of the study was the evaluation of the influence of various
      clinical and sociodemographic factors on the perception of quality of life in 141
      patients with depression (CIE-10). We used a multivariate analysis of logistic
      regression to predict lower quality of life and well-being. The best predictive
      variables for quality of life were the Hamilton Rating Scale for Depression (HAM
      D) score, the number of episodes, personality disorder and gender. For well
      being, the best predictive variables were HAM-D score, type of family
      environment, Hamilton Rating Scale for Anxiety (HAM-A) score, educational level
      and marital status. We conclude that the severity of the symptoms is the main
      factor influencing the appraisal of the quality of life, while sociodemographic
      variables play a more limited role. 

PMID- 24945066
TI  - Screening for adjustment disorders and major depression in otolaryngology
      patients using the Hospital Anxiety and Depression Scale.
AB  - The authors conducted a study to demonstrate the prevalence of psychiatric
      symptoms among 100 otolaryngology inpatients (50 with non-malignant conditions;
      50 with malignancies), and to investigate the efficacy of the Hospital Anxiety
      and Depression Scale (HADS) as a screening test for psychiatric disorders in
      otolaryngology. A structured interview was conducted according to the Adjustment
      Disorders and Major Depressive Episodes section of DSM-N, which demonstrated that
      30% of the inpatients with benign diseases met the criteria for some psychiatric
      disorders (one patient for major depression and 14 for adjustment disorders) and
      that 46% of the inpatients with malignancies met the criteria (nine patients for
      major depression and 14 for adjustment disorders). There were highly significant
      differences between the HADS scores of the patients with psychiatric disorders
      and those without. Comparing the sensitivity and the specificity using the HADS
      as a screening test, the optimal cut-off point was 12, which produced 92%
      sensitivity, 90% specificity and 85% positive predictive value (PPV) among not
      only non-malignant and malignant cases taken together but also among malignant
      cases only. 

PMID- 24945067
TI  - The effect of clozapine on aggressive behaviour in patients with chronic
      schizophrenia.
AB  - We studied the effect of 12 months' treatment with clozapine (150-400 mg/day) in
      16 chronic schizophrenic patients with aggressive behaviour. The number of
      aggressive episodes, the time spent in seclusion and physical restraint, and the
      number of pharmacological interventions used as chemical restraint during the 12
      months of clozapine treatment were calculated and compared to those for the
      previous 12-month period (during which treatment was with conventional
      antipsychotics). During clozapine therapy there was a statistically significant
      decrease (P<0.001) in all the parameters of aggressive behaviour which we
      investigated, as compared with the pre-clozapine period. The reduction in
      aggressive behaviour was more prominent within the first 6 months of clozapine
      administration. Clozapine treatment was also associated with a global improvement
      in psychosis, as measured by the Brief Psychiatric Rating Scale. Despite the
      limitations in sample size and study design, our results confirm that clozapine
      appears more effective than classical antipsychotics in reducing aggressive
      behaviour in chronic schizophrenic patients. 

PMID- 24945068
TI  - Prolonged hypertension: A case report of a potential interaction between
      electroconvulsive therapy and venlafaxine.
AB  - Electroconvulsive therapy is often given in addition to antidepressant drugs when
      there has been an inadequate response to the latter. In the case of tricyclic
      antidepressants and monoamine oxidase inhibitors, this is not regarded as a
      hazardous combination. Caution is however advised with selective serotonin re
      uptake inhibitors, since there may be a prolongation of seizures. Cardiovascular
      complications resulting from the combination of ECT and antidepressant medication
      have not been previously reported. We report on a case of prolonged hypertension
      following ECT in a patient taking the serotonin and noradrenaline re-uptake
      inhibitor, venlafaxine. Possible mechanisms for this potentially very serious
      interaction are discussed. 

PMID- 24945069
TI  - Patients who changed my practice: Mental disorders in late life-issues of
      diagnosis and management.
AB  - The author's interest in old age psychiatry was fostered by cases such as the
      three he describes. This sub-speciality is different, challenging and enjoyable. 

PMID- 24945070
TI  - Correspondence.

PMID- 24945073
TI  - A stress-responsive Escherichia coli protein, CysQ is a highly effective
      solubility enhancer for aggregation-prone heterologous proteins.
AB  - When used as an N-terminal fusion expression partner, the Escherichia coli stress
      responsive protein, CysQ dramatically increased the cytoplasmic solubility of
      various aggregation-prone heterologous proteins: Pseudomonas putida cutinase
      (CUT), human granulocyte colony-stimulating factor (hG-CSF), human ferritin light
      chain (hFTN-L), arginine deiminase (ADI), human interleukin-2 (IL2), human
      activation induced cytidine deaminase (AID), and deletion mutant of human
      glutamate decarboxylase (GAD448-585). As compared with well-known fusion tags
      such as glutathione-S-transferase (GST) and maltose-binding protein (MBP), the
      performance of CysQ as solubility enhancer was evidently better than GST and was
      similar to or better than MBP for the seven heterologous proteins above. This is
      likely due to the intrinsic ability of CysQ to form its native conformation,
      probably promoting the binding of molecular chaperones during the folding of CysQ
      fusion protein. When used as a substrate, p-nitrophenyl butyrate (PNB) was
      successfully hydrolyzed to p-nitrophenol by CysQ-CUT fusion mutant. Even after
      CysQ was removed, the solubility of hFTN-L and hG-CSF, the secondary structure of
      hG-CSF, and self-assembly activity of hFTN-L were successfully maintained.
      Conclusively, it seems that CysQ is a highly effective solubility enhancer and
      fusion expression partner for the production of a variety of bio-active
      recombinant proteins.

PMID- 24945074
TI  - The fatty acid transport protein Fat1p is involved in the export of fatty acids
      from lipid bodies in Yarrowia lipolytica.
AB  - In order to live, cells need to import different molecules, such as sugars, amino
      acids or lipids, using transporters. In Saccharomyces cerevisiae, the ScFAT1 gene
      encodes the long-chain fatty acid transporter; however, the transport of fatty
      acids (FAs) in the oleaginous yeast Yarrowia lipolytica has not yet been studied.
      In contrast to what has previously been found for DeltaScfat1 strains,
      DeltaYlfat1 yeast was still able to grow on substrates containing short-, medium-
      or long-chain FAs. We observed a notable difference in cell lipid content between
      wild-type (WT) and deletion mutant strains after 24 h of culture in minimal
      oleate medium: in the WT strain, lipids represented 24% of cell dry weight (CDW),
      while they accounted for 37% of CDW in the DeltaYlfat1 strain. This result
      indicates that YlFat1p is not involved in cell lipid uptake. Moreover, we also
      observed that fatty acid remobilisation was decreased in the DeltaYlfat1 strain
      and that fluorescence-tagged YlFat1p proteins localised to the interfaces between
      lipid bodies, which suggests that YlFat1p may play a role in the export of FAs
      from lipid bodies. 

PMID- 24945076
TI  - Demodex lutrae n. sp. (Acari) in European otter Lutra lutra (Carnivora:
      Mustelidae) with data from other demodecid mites in carnivores.
AB  - This article describes morphological characteristics and occurrence of Demodex
      lutrae n. sp., which was found on European otter Lutra lutra (Linnaeus, 1758) in
      Poland. The new species was found in hairy regions of otter skin, mainly in the
      head area. With respect to morphological features, D. lutrae is most similar to
      D. canis (Leydig, 1859) from the domestic dog Canis familiaris Linnaeus, 1758.
      The new species is a medium-sized demodecid mite (adult stages average 200 MUm in
      length); characteristic features of these mites are hammer-shaped supracoxal
      spines (setae elc.p) on dorsal side of gnathosoma and palps with 3 conical
      spines. Demodex lutrae is the first representative of the family Demodecidae
      described in a host from the subfamily Lutrinae. This paper also contains a
      checklist of demodecid mites known from carnivores.

PMID- 24945075
TI  - The cholinergic basal forebrain in the ferret and its inputs to the auditory
      cortex.
AB  - Cholinergic inputs to the auditory cortex can modulate sensory processing and
      regulate stimulus-specific plasticity according to the behavioural state of the
      subject. In order to understand how acetylcholine achieves this, it is essential
      to elucidate the circuitry by which cholinergic inputs influence the cortex. In
      this study, we described the distribution of cholinergic neurons in the basal
      forebrain and their inputs to the auditory cortex of the ferret, a species used
      increasingly in studies of auditory learning and plasticity. Cholinergic neurons
      in the basal forebrain, visualized by choline acetyltransferase and p75
      neurotrophin receptor immunocytochemistry, were distributed through the medial
      septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial
      tracer deposits and injections of the immunotoxin ME20.4-SAP (monoclonal antibody
      specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory
      cortex showed that cholinergic inputs originate almost exclusively in the
      ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis
      revealed a pattern of labelled fibres and terminal fields that resembled
      acetylcholinesterase fibre staining in the auditory cortex, with the heaviest
      labelling in layers II/III and in the infragranular layers. Labelled fibres with
      small en-passant varicosities and simple terminal swellings were observed
      throughout all auditory cortical regions. The widespread distribution of
      cholinergic inputs from the nucleus basalis to both primary and higher level
      areas of the auditory cortex suggests that acetylcholine is likely to be involved
      in modulating many aspects of auditory processing. 

PMID- 24945078
TI  - Ear, nose and throat foreign bodies: the experience of the Pediatric Hospital of
      Turin.
AB  - AIM: Ear, nose and throat (ENT) foreign body (FB) injuries represent an emerging
      problem in the paediatric population because of their human and social costs. The
      aim of the study is the site-specific evaluation of FB injuries in the paediatric
      population referred to the emergency department of the Pediatric Hospital of
      Turin. METHODS: This retrospective analysis was carried out sifting medical
      reports between 2002 and 2011. We collected information about 338 patients' FB
      characteristics, complications and hospitalisation. RESULTS: The mean age was 4.2
      +/- 2.9 years. Nose and ear are the most involved anatomical sites, followed by
      pharynx, oesophagus and trachea-bronchi. The most common FBs are balls, beads and
      toys parts (29.6%), followed by fishbones (13.6%). A lower mean age is observed
      in tracheo-bronchial and oesophageal FBs. The 9.2% of cases reported
      complications. CONCLUSIONS: A quick and proper diagnosis followed by an effective
      treatment of FB injuries and their complication is mandatory. Surveillance
      registries have a key role in prevention and management of FB injuries; useful
      information can be obtained also for nurse and ENT specialist training in order
      to create professionals ready to recognise and manage FB injuries in the most
      effective way.

PMID- 24945077
TI  - Managing high-risk surgical patients: modifiable co-morbidities matter.
AB  - BACKGROUND: There are a subset of potentially modifiable co-morbidities that may
      be targeted in the preoperative phase with a view to optimizing control and
      improving post-operative outcomes. This study aims to estimate the effect of
      potentially modifiable co-morbidities on post-operative outcomes and to identify
      potential targets for preoperative management. METHODS: Retrospective data on
      hospital separations in South Australia were analyzed using multiple regression
      to estimate the association between nine potentially modifiable co-morbidities
      and length of stay, post-operative complications and in-hospital mortality.
      RESULTS: After adjusting for primary diagnosis, age, gender and other potential
      confounders, significant increases in length of stay and complications were
      recorded for eight and six of the nine modifiable co-morbidities, respectively.
      As examples, previous heart failure was associated with a 54% increase in length
      of stay and an odds ratio of 1.75 for complications. Asthma and chronic
      obstructive pulmonary disease was associated with a 38% increase in length of
      stay and an odds ratio of 1.64 for complications. CONCLUSIONS: A set of
      potentially modifiable co-morbidities is associated with a range of poorer post
      operative outcomes, relative to patients without those co-morbidities. There is a
      clinical rationale that outcomes will be worse in the subset of patients for whom
      such co-morbidities are poorly controlled, and that timely intervention to
      improve control in the period prior to surgery will improve post-operative
      outcomes. Further research is required on post-operative outcomes for patients
      with and without controlled co-morbidities and on the effects of timely
      intervention to improve control prior to surgery.

PMID- 24945080
TI  - Electrostatically tuned self-assembly of branched amphiphilic peptides.
AB  - Electrostatics plays an important role in the self-assembly of amphiphilic
      peptides. To develop a molecular understanding of the role of the electrostatic
      interactions, we develop a coarse-grained model peptide and apply self-consistent
      field theory to investigate the peptide assembly into a variety of aggregate
      nanostructures. We find that the presence and distribution of charged groups on
      the hydrophilic branches of the peptide can modify the molecular configuration
      from extended to collapsed. This change in molecular configuration influences the
      packing into spherical micelles, cylindrical micelles (nanofibers), or planar
      bilayers. The effects of charge distribution therefore have important
      implications for the design and utility of functional materials based on
      peptides. 

PMID- 24945079
TI  - Blockade of the T cell immunoglobulin and mucin domain protein 3 pathway
      exacerbates sepsis-induced immune deviation and immunosuppression.
AB  - Sepsis is a life-threatening condition, but the pathophysiological basis and
      biomarkers for the monitoring of sepsis and as targets for therapy remain to be
      determined. We have shown previously that T cell immunoglobulin and mucin domain
      protein 3 (Tim-3), a negative immune regulator, is involved in the
      physiopathology of sepsis, but the underlying mechanisms remain unclear. In the
      present study, we showed that Tim-3 signalling modulated the response patterns of
      both macrophages and T helper cells in sepsis. Blockade of the Tim-3 pathway
      exacerbated sepsis-induced proinflammatory macrophage responses and lymphocyte
      apoptosis during the early phase of sepsis, and enhanced the shift to anti
      inflammatory responses for both macrophages and T helper cells during the late
      phase of sepsis. Tim-3 signalling was found to regulate CD80 and CD86 expression
      on macrophages both in vivo and in vitro. Co-culture of T cells with Tim-3 knock
      down macrophages led to a biased T helper type 2 (Th2) response, partially
      explaining how Tim-3 signalling shapes inflammation patterns in vivo. Further
      studies on this pathway might shed new light on the pathogenesis of sepsis and
      suggest new approaches for intervention.

PMID- 24945081
TI  - Noninvasive assessment of endothelial function: the classic methods and the new
      peripheral arterial tonometry.
AB  - The combination of risk stratification by assessment of conventional risk factors
      for cardiovascular disease (CVD) with not only a morphological assessment of
      vascular damage (such as carotid ultrasound examination) but also vascular
      function tests may be a useful strategy for the management of CVD and its related
      risk factors. Endothelial dysfunction is present in a great variety of
      pathological conditions: it is considered the first alteration of vascular
      function in atherosclerosis and one of the phenomena involved in the progression
      of heart failure. Assessing endothelial function with noninvasive methods could
      have a central role for evaluation of treatment, prognostic stratification, and
      pharmacological studies in CVD. In this review, we focus on noninvasive
      techniques that have recently become available to assess endothelial function and
      express the possible clinical role in different clinical settings. 

PMID- 24945083
TI  - Obesity paradox: does fat alter outcomes in chronic obstructive pulmonary
      disease?
AB  - The role of obesity and its influence on mortality in the general population has
      been well established. However, over the last decade, there has been substantial
      focus on the paradox that exists among the obese with various chronic diseases,
      where overweight and at least mild-moderately obese with these chronic diseases
      appear to have a better prognosis than do their leaner counterparts. Among them,
      congestive heart failure and coronary heart disease have received considerable
      attention. However, the influence of the obesity paradox on outcomes among
      patients with chronic obstructive pulmonary disease (COPD), including those
      requiring long-term oxygen therapy, has not been elucidated. This paper
      highlights the current research in this area and brings to light the lacunae that
      exists with regard to this paradox in COPD.

PMID- 24945082
TI  - Anesthesia for euthanasia influences mRNA expression in healthy mice and after
      traumatic brain injury.
AB  - Tissue sampling for gene expression analysis is usually performed under general
      anesthesia. Anesthetics are known to modulate hemodynamics, receptor-mediated
      signaling cascades, and outcome parameters. The present study determined the
      influence of anesthetic paradigms typically used for euthanization and tissue
      sampling on cerebral mRNA expression in mice. Naive mice and animals with acute
      traumatic brain injury induced by controlled cortical impact (CCI) were
      randomized to the following euthanasia protocols (n=10-11/group): no anesthesia
      (NA), 1 min of 4 vol% isoflurane in room air (ISO), 3 min of a combination of 5
      mg/kg midazolam, 0.05 mg/kg fentanyl, and 0.5 mg/kg medetomidine
      intraperitoneally (COMB), or 3 min of 360 mg/kg chloral hydrate intraperitoneally
      (CH). mRNA expression of actin-1-related gene (Act1), FBJ murine osteosarcoma
      viral oncogene homolog B (FosB), tumor necrosis factor alpha (TNFalpha), heat
      shock protein beta-1 (HspB1), interleukin (IL)-6, tight junction protein 1 (ZO
      1), IL-1beta, cyclophilin A, micro RNA 497 (miR497), and small cajal body
      specific RNA 17 were determined by real-time polymerase chain reaction (PCR) in
      hippocampus samples. In naive animals, Act1 expression was downregulated in the
      CH group compared with NA. FosB expression was downregulated in COMB and CH
      groups compared with NA. CCI reduced Act1 and FosB expression, whereas HspB1 and
      TNFalpha expression increased. After CCI, HspB1 expression was significantly
      higher in ISO, COMB, and CH groups, and TNFalpha expression was elevated in ISO
      and COMB groups. MiR497, IL-6, and IL-1beta were upregulated after CCI but not
      affected by anesthetics. Effects were independent of absolute mRNA copy numbers.
      The data demonstrate that a few minutes of anesthesia before tissue sampling are
      sufficient to induce immediate mRNA changes, which seem to predominate in the
      early-regulated gene cluster. Anesthesia-related effects on gene expression might
      explain limited reproduciblity of real-time PCR data between studies or research
      groups and should therefore be considered for quantitative PCR data.

PMID- 24945084
TI  - Journal of Child and Adolescent Psychopharmacology. From the editor-in-chief's
      desk.

PMID- 24945085
TI  - Guanfacine extended release adjunctive to a psychostimulant in the treatment of
      comorbid oppositional symptoms in children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of guanfacine
      extended release (GXR) adjunctive to a psychostimulant on oppositional symptoms
      in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
      METHODS: A multicenter, double-blind, placebo-controlled dose-optimization study
      of GXR (1-4 mg/d) or placebo administered morning (a.m.) or evening (p.m.)
      adjunctive to psychostimulant was conducted in subjects ages 6-17 with suboptimal
      response to psychostimulant alone. Suboptimal response was defined as treatment
      with a stable dose of psychostimulant for >=4 weeks with ADHD Rating Scale IV
      total score >=24 and Clinical Global Impressions-Severity of Illness score >=3,
      as well as investigator opinion. Primary efficacy and safety results have been
      reported previously. Secondary efficacy measures included the oppositional
      subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L); these
      are reported herein. RESULTS: Significant reductions from baseline to the final
      on-treatment assessment on the oppositional subscale of the CPRS-R:L were seen
      with GXR plus psychostimulant compared with placebo plus psychostimulant, both in
      the overall study population (placebo-adjusted least squares [LS] mean change
      from baseline to the final on-treatment assessment: GXR a.m.+psychostimulant, 
      2.4, p=0.001; GXR p.m.+psychostimulant, -2.2, p=0.003) as well as in the subgroup
      of subjects with significant baseline oppositional symptoms (GXR
      a.m.+psychostimulant, -3.6, p=0.001; GXR p.m.+psychostimulant, -2.7, p=0.013).
      Treatment-emergent adverse events were reported by 77.3%, 76.3%, and 63.4% of
      subjects in the GXR a.m., GXR p.m., and placebo groups, respectively, in the
      overall study population. CONCLUSIONS: GXR adjunctive to a psychostimulant
      significantly reduced oppositional symptoms compared with placebo plus a
      psychostimulant in subjects with ADHD and a suboptimal response to
      psychostimulant alone.

PMID- 24945087
TI  - Psychotic symptoms and catatonia in a preadolescent boy with autism spectrum
      disorder.

PMID- 24945086
TI  - Concordance between parent and physician medication histories for children and
      adolescents with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: It is necessary for both clinicians and researchers who study
      attention-deficit/hyperactivity disorder (ADHD) to obtain a medication history
      for patients/participants for a variety of purposes. Because of the complexity of
      constructing medication histories using official records, parental report of
      medication for children with ADHD is the most commonly used source of
      information. However, the reliability and validity of parent reports of
      medication history have not been thoroughly studied. Previous studies have only
      examined the psychometrics of interview assessments of medication use for a
      maximum of a 12 month recall period. The current study compares parent report
      provided by a questionnaire and physician records for children and adolescents
      with ADHD. This is the first study to examine validity of retrospective recall
      for an extended medication history (prekindergarten-12th grade) using a
      questionnaire, and the first to examine validity of parental report of dosage.
      METHODS: Participants with ADHD were part of the Pittsburgh ADHD Longitudinal
      Study. The current study utilized data from those in the ADHD group who had at
      least 1 year of data from the physician's records and corresponding records from
      the parent (n=178). RESULTS: Percent agreement for medication use was >80%.
      Intraclass correlation coefficients for parent-provider agreement on total daily
      dosage of ADHD medications were in the good to excellent range. There were no
      significant predictors of agreement. CONCLUSIONS: Our findings indicate that it
      is acceptable for clinics and research studies to obtain information about
      medication use for children with ADHD retrospectively solely based on parental
      report.

PMID- 24945089
TI  - Implant Injury Case Series and Review of the Literature Part 1: Inferior Alveolar
      Nerve Injury.
AB  - Injury to adjacent structures is an unfortunate and avoidable outcome of oral
      implant placement surgery. Paramount among these is perforation into paranasal
      sinus; into neighboring tooth root; through cortical plate; and into vessels,
      canals, and, most importantly, nerves. In most cases, injudicious oral implant
      placement can be attributed to poor treatment planning. We present the cases of
      several patients referred for postsurgical radiology that illustrate injury to
      the inferior alveolar canal by implant impingement, penetration, and even
      complete obliteration of the nerve and canal in the absence of proper treatment
      planning and imaging modalities. The authors stress the importance of thorough
      implant case preparation and planning, which may include the use of cone beam
      computerized tomography in order to minimize nerve injury. 

PMID- 24945090
TI  - Common cold symptoms in children: results of an Internet-based surveillance
      program.
AB  - BACKGROUND: Conducting and analyzing clinical studies of cough and cold
      medications is challenging due to the rapid onset and short duration of the
      symptoms. The use of Internet-based surveillance tools is a new approach in
      clinical studies that is gradually becoming popular and may become a useful
      method of recruitment. As part of an initiative to assess the safety and efficacy
      of cough and cold ingredients in children 6-11 years of age, a surveillance
      program was proposed as a means to identify and recruit pediatric subjects for
      clinical studies. OBJECTIVE: The objective of the study was to develop an
      Internet-based surveillance system and to assess the feasibility of using such a
      system to recruit children for common cold clinical studies, record the natural
      history of their cold symptoms, and determine the willingness of parents to have
      their children participate in clinical studies. METHODS: Healthy potential
      subjects were recruited via parental contact online. During the 6-week
      surveillance period, parents completed daily surveys to record details of any
      cold symptoms in their children. If a child developed a cold, symptoms were
      followed via survey for 10 days. Additional questions evaluated the willingness
      of parents to have their children participate in a clinical study shortly after
      onset of symptoms. RESULTS: The enrollment target of 248 children was reached in
      approximately 1 week. Children from 4 distinct geographic regions of the United
      States were recruited. Parents reported cold symptoms in 163 children, and 134
      went on to develop colds. The most prevalent symptoms were runny nose, stuffed-up
      nose, and sneezing. The most severe symptoms were runny nose, stuffed-up nose,
      and sore/scratchy throat. The severity of most symptoms peaked 1-2 days after
      onset. Up to 54% of parents expressed willingness to bring a sick child to a
      clinical center shortly after the onset of symptoms. Parents found the Internet
      based surveys easy to complete. CONCLUSIONS: Internet-based surveillance and
      recruitment can be useful tools to follow colds in children and enroll subjects
      in clinical studies. However, study designs should account for a potentially high
      dropout rate and low rate of adherence to study procedures.

PMID- 24945092
TI  - CD40-mediated amplification of local immunity by epithelial cells is impaired by
      HPV.
AB  - The interaction between the transmembrane glycoprotein surface receptor CD40
      expressed by skin epithelial cells (ECs) and its T-cell-expressed ligand CD154
      was suggested to exacerbate inflammatory skin diseases. However, the full
      spectrum of CD40-mediated effects by ECs underlying this observation is unknown.
      Therefore, changes in gene expression after CD40 ligation of ECs were studied by
      microarrays. CD40-mediated activation for 2 hours stimulated the expression of a
      coordinated network of immune-involved genes strongly interconnected by IL8 and
      TNF, whereas after 24 hours anti-proliferative and anti-apoptotic genes were
      upregulated. CD40 ligation was associated with the production of chemokines and
      the attraction of lymphocytes and myeloid cells from peripheral blood mononuclear
      cells (PBMCs). Thus, CD40-mediated activation of ECs resulted in a highly
      coordinated response of genes required for the local development and sustainment
      of adaptive immune responses. The importance of this process was confirmed by a
      study on the effects of human papilloma virus (HPV) infection to the EC's
      response to CD40 ligation. HPV infection clearly attenuated the magnitude of the
      response to CD40 ligation and the EC's capacity to attract PBMCs. The fact that
      HPV attenuates CD40 signaling in ECs indicates the importance of the CD40-CD154
      immune pathway in boosting cellular immunity within epithelia. 

PMID- 24945093
TI  - Innate immune cell-produced IL-17 sustains inflammation in bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune skin disease characterized by the
      binding of autoantibodies to components of the hemidesmosome structure, resulting
      in an inflammatory response and subepidermal blister formation. To investigate
      the role of immune orientation in the inflammatory processes associated with
      disease progression, blister fluid, serum, and biopsy specimens were collected
      from 31 consecutive BP patients. Blister fluids displayed high levels of IL-6, IL
      17, IL-22, and IL-23, whereas transforming growth factor-beta was increased in BP
      sera. However, neither immunocytochemistry on a trans-differentiation model of IL
      17-producing peripheral blood mononuclear cells nor immunohistochemistry on BP
      biopsy specimens could demonstrate the presence of T helper type 17 lymphocytes.
      Instead, innate immune cells, especially neutrophils, produced IL-17 at the skin
      lesional site. Of note, superpotent topical corticosteroid application quickly
      and markedly reduced both IL-17 expression and clinical signs of BP.
      Consistently, IL-17 upregulated matrix-metalloprotease-9 and neutrophil elastase
      expression, two proteases involved in blister formation, thereof further
      demonstrating its role in the progress of BP. Finally, IL-17-induced matrix
      degradation, originated from neutrophil activation, initiated the formation of an
      amplification loop of the inflammatory response that could represent the
      underlying phenomenon leading to the maintenance and even disease extent. Thus,
      our results could open new therapeutic strategies for BP patients. 

PMID- 24945095
TI  - Beyond the active site: the impact of the outer coordination sphere on
      electrocatalysts for hydrogen production and oxidation.
AB  - Redox active metalloenzymes play a major role in energy transformation reactions
      in biological systems. Examples include formate dehydrogenases, nitrogenases, CO
      dehydrogenase, and hydrogenases. Many of these reactions are also of interest to
      humans as potential energy storage or utilization reactions for
      photoelectrochemical, electrolytic, and fuel cell applications. These
      metalloenzymes consist of redox active metal centers where substrates are
      activated and undergo transformation to products accompanied by electron and
      proton transfer to or from the substrate. These active sites are typically buried
      deep within a protein matrix of the enzyme with channels for proton transport,
      electron transport, and substrate/product transport between the active site and
      the surface of the protein. In addition, there are amino acid residues that lie
      in close proximity to the active site that are thought to play important roles in
      regulating and enhancing enzyme activity. Directly studying the outer
      coordination sphere of enzymes can be challenging due to their complexity, and
      the use of modified molecular catalysts may allow us to provide some insight.
      There are two fundamentally different approaches to understand these important
      interactions. The "bottom-up" approach involves building an amino acid or peptide
      containing outer coordination sphere around a functional molecular catalyst, and
      the "top-down" approach involves attaching molecular catalyst to a structured
      protein. Both of these approaches have been undertaken for hydrogenase mimics and
      are the emphasis of this Account. Our focus has been to utilize amino acid or
      peptide based scaffolds on an active functional enzyme mimic for H2 oxidation and
      production, [Ni(P(R)2N(R('))2)2](2+). This "bottom-up" approach has allowed us to
      evaluate individual functional group and structural contributions to
      electrocatalysts for H2 oxidation and production. For instance, using amine,
      ether, and carboxylic acid functionalities in the outer coordination sphere
      enhances proton movement and results in lower catalytic overpotentials for H2
      oxidation, while achieving water solubility in some cases. Amino acids with
      acidic and basic side chains concentrate substrate around catalysts for H2
      production, resulting in up to 5-fold enhancements in rate. The addition of a
      structured peptide in an H2 production catalyst limited the structural freedom of
      the amino acids nearest the active site, while enhancing the overall rate.
      Enhanced stability to oxygen or extreme conditions such as strongly acidic or
      basic conditions has also resulted from an amino acid based outer coordination
      sphere. From the "top-down" approach, others have achieved water solubility and
      photocatalytic activity by associating this core complex with photosystem-I.
      Collectively, by use of this well understood core, the role of individual and
      combined features of the outer coordination sphere are starting to be understood
      at a mechanistic level. Common mechanisms have yet to be defined to predictably
      control these processes, but our growing knowledge in this area is essential for
      the eventual mimicry of enzymes by efficient molecular catalysts for practical
      use.

PMID- 24945096
TI  - Copper-catalyzed regio- and stereoselective O-arylation of enolates.
AB  - Copper-catalyzed O-arylation of enolates with diaryliodonium salts as arylating
      reagents was realized successfully. As important building blocks, beta-aryloxy
      carbonyl compounds were obtained in up to 98% yield under mild conditions, and
      complete control of O-arylation and Z-stereoselectivity were achieved. The origin
      of the selectivity was also discussed. 

PMID- 24945097
TI  - Patterns and predictors of follow-up in patients with mild traumatic brain
      injury.
AB  - BACKGROUND: This study was undertaken to identify factors that influence follow
      up for patients with mild traumatic brain injury (MTBI). METHODS: One hundred and
      ninety-nine consecutive inpatients diagnosed with MTBI at a Trauma Centre (or TC)
      were monitored for establishment of care with a brain injury specialist after
      discharge. Bivariate statistics were calculated to determine subject
      characteristics impacting the decision to pursue TBI-related specialty care.
      RESULTS: One hundred and nineteen patients (59.8%) followed up with the TC for
      routine post-injury care. Patients who followed up were older (age >40: OR =
      2.48, p = 0.01, 95% CI = 1.03-8.96) and had longer hospital lengths of stay (LOS
      > 3 days: OR = 2.99, p < 0.001, 95% CI = 1.33-7.67). Upon follow-up, providers
      identified 20 patients (16.8%) with persistent neurologic symptoms, seven (3.5%)
      of whom saw a brain injury specialist. Lack of insurance significantly decreased
      the likelihood of follow-up with the TC and/or establishment of care with a TBI
      specialist. (OR = 0.76, p = 0.01, 95% CI = 0.62-0.95). CONCLUSIONS: Being insured
      was strongly predictive for follow-up at the TC and for establishing with a brain
      injury specialist post-MTBI. The TC post-injury visit identified MTBI patients
      with persistent symptoms, suggesting post-acute TC follow-up is an important
      venue for MTBI sequelae screening and referral.

PMID- 24945094
TI  - The IL-17A-producing CD8+ T-cell population in psoriatic lesional skin comprises
      mucosa-associated invariant T cells and conventional T cells.
AB  - IL-17A is pivotal in the etiology of psoriasis, and CD8(+) T cells with the
      ability to produce this cytokine (Tc17 cells) are over-represented in psoriatic
      lesions. Here we demonstrate that the frequency of Tc17 cells in peripheral blood
      of psoriasis patients correlated with the clinical severity of the disease.
      Analysis of cutaneous-associated lymphocyte antigen expression showed that the
      blood Tc17 population contains a significantly higher proportion of cells with
      skin-homing potential compared with the CD8(+) T-cell population lacking IL
      17A/IL-22 expression. IL-17A-producing CD8(+) T cells in blood have previously
      been reported to belong mainly to the mucosa-associated invariant T-cell (MAIT
      cell) lineage characterized by TCR Valpha7.2 chain, CD161, IL-18Ralpha, and
      multidrug transporter ABCB1 expression. We demonstrate the presence of CD8(+)
      MAIT cells in the dermis and epidermis of psoriatic plaques, as well as healthy
      skin; however, IL-17A-producing CD8(+) MAIT cells were predominantly found in
      psoriatic skin. Notably, we observed IL-17A production in a large proportion of
      psoriatic plaque-derived CD8(+) T cells devoid of MAIT cell characteristics,
      likely representing conventional CD8(+) T cells. In conclusion, we provide
      supporting evidence that implicates Tc17 cells in the pathogenesis of psoriasis
      and describe the presence of innate CD8(+) MAIT cells in psoriatic lesions as an
      alternative source of IL-17A. 

PMID- 24945098
TI  - Influence of CYP1A1*2C on high triglyceride levels in female Mexican indigenous
      Tarahumaras.
AB  - BACKGROUND AND AIMS: High triglyceride levels are closely related to
      cardiovascular disease. Its development lays on age, diet, physical activity,
      ethnicity and genetic factors. Among the last, the CYP1A1*2C allele has an
      influence on the metabolism of cholesterol and other fatty acids. We undertook
      this study to determine the frequency of CYP1A1*2C and its association with
      triglyceride levels in Mexican indigenous Tarahumaras and Tepehuanos. METHODS:
      Anthropometric and biochemical data were recorded. Genotyping of CYP1A1*2C by RT
      PCR was done in 110 Tepehuano, 69 Tarahumara and 64 Mestizo. RESULTS: Significant
      differences in age, waist diameter, BMI, creatinine, glucose, cholesterol,
      triglycerides, HDL and VLDL measurements were found between Tarahumaras and
      Tepehuanos (p <0.05). Additionally, Tarahumara women showed the highest values of
      waist diameter, BMI and triglycerides (p <0.05). It was found that Tarahumaras
      showed a significant association between high triglyceride levels and CYP1A1*2C
      allele (OR = 2.57; 95% CI 1.12-5.88, p = 0.024) under a recessive inheritance
      model. However, the Tepehuano group showed a significant protective association
      between normal triglyceride levels and CYP1A1*2C polymorphism (OR = 0.28; 95% CI
      0.10-0.80, p = 0.015) following a dominant inheritance model. The same pattern
      was observed after analysis with females of both ethnicities. CONCLUSION: A
      significant association between CYP1A1*2C and high triglyceride levels in
      Amerindian Tarahumaras from Chihuahua has been found; this allele was
      significantly associated with normal triglyceride levels in Tepehuanos from
      Durango, Mexico. Further studies are needed to elucidate the genetic role of
      CYP1A1 in cardiovascular disease susceptibility.

PMID- 24945099
TI  - Reliability study of thermal quantitative sensory testing in healthy Chinese.
AB  - BACKGROUND: Test-retest reliability is important to establish for any diagnostic
      tool. The reliability of quantitative sensory testing (QST) in the trigeminal
      region has recently been described in Caucasians as well as differences in
      absolute thresholds and responses between Caucasians and Chinese. However, the
      test-retest reliability has not been determined in a Chinese population.
      OBJECTIVE: To provide novel information on the test-retest reliability of thermal
      QST in the trigeminal and spinal system in healthy Chinese. METHODS: Twenty
      healthy volunteers (10 women and 10 men) participated. Cold detection threshold
      (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain
      threshold (HPT) were measured at two sites: the surface of the left hand and the
      left masseter. The testing was performed over three consecutive stimuli trials,
      three sessions conducted on one day and repeated one week later. Data were
      analyzed with intra-tester reliability test and four-way analysis of variance
      (ANOVA) for repeated measures. RESULTS: There was a tendency for the first trial
      in CDT (p = 0.005), CPT (p = 0.02), and HPT (p < 0.001) to reflect higher
      sensitivity than the subsequent two trials. Most variables showed acceptable to
      excellent reliability and non-significant difference across different trials
      (ICC: 0.912-0.989), sessions (ICC: 0.791-0.977), and days (ICC: 0.415-0.837).
      Between-site differences were significant for CDT (p = 0.003) and HPT (p = 0.045)
      with higher sensitivity at the masseter muscle. There were significant gender
      differences with higher sensitivity in women for CPT (p = 0.001) and HPT (p =
      0.001). CONCLUSION: Test site and gender affect thermal thresholds substantially.
      The test-retest reliability of most thermal threshold measures were acceptable
      for assessing somatosensory function, however, innocuous thresholds appear to be
      associated with larger variability than noxious thresholds in a Chinese
      population.

PMID- 24945100
TI  - Levels of oestrogen receptor, progesterone receptor and alphaB-crystallin in
      eutopic endometrium in relation to pregnancy in women with endometriosis.
AB  - Endometriosis affects fertility in many women and may partly be due to decreased
      endometrial receptivity. Several mechanisms have been suggested, notably,
      progesterone resistance for which a number of candidate biomarkers have been
      suggested. Here we demonstrate aberrant levels of steroid hormone receptors and
      the small heat shock protein alphaB-crystallin in eutopic endometrial epithelium
      from 38 women with peritoneal endometriosis diagnosed during investigation for
      secondary infertility. Spontaneous pregnancies within 1 year after medical and
      surgical treatment for endometriosis were recorded and semi-quantitative
      immunohistochemistry data compared between women with endometriosis who did or
      did not become pregnant and healthy controls. Stronger immunostaining for ER
      alpha was detected in luminal and glandular endometrial epithelium from women
      with endometriosis who did not become pregnant during the post-treatment
      observation period versus endometriosis patients who became pregnant and
      controls. Staining levels of PR and PR-B were lower in patients without
      subsequent pregnancies than in the two other groups. Endometrial levels of alphaB
      crystallin in endometriosis patients similar to those in controls were strongly
      correlated with the chance of becoming pregnant, whereas higher or lower levels
      were not. 

PMID- 24945101
TI  - Structural diversity of polyoxomolybdate clusters along the three-fold axis of
      the molybdenum storage protein.
AB  - The molybdenum storage protein (MoSto) can store more than 100 Mo or W atoms as
      discrete polyoxometalate (POM) clusters. Here, we describe the three POM cluster
      sites along the threefold axis of the protein complex based on four X-ray
      structures with slightly different polyoxomolybdate compositions between 1.35 and
      2 A resolution. In contrast to the Moalpha-out binding site occupied by an Mo3
      cluster, the Moalpha-in and Mobeta binding sites contain rather weak and non
      uniform electron density for the Mo atoms (but clearly identifiable by anomalous
      data), suggesting the presence of POM cluster ensembles and/or degradation
      products of larger aggregates. The "Moalpha-in cluster ensemble" was interpreted
      as an antiprism-like Mo6 species superimposed with an Mo7 pyramide and the
      "Mobeta cluster ensemble" as an Mo13 cluster (present mostly in a degraded form)
      composed of a pyramidal Mo7 and a Mo3 building block linked by three spatially
      separated MoOx units. Inside the ball-shaped Mo13 cluster sits an occluded
      central atom, perhaps a metal ion. POM cluster formation at the Moalpha-in and
      Mobeta sites appears to be driven by filtering out and binding/protecting self
      assembled transient species complementary to the protein template.

PMID- 24945104
TI  - Multiple health risk behaviour in Czech adolescents: family, school and
      geographic factors.
AB  - The study examines the relationship of family, school and geographic factors in
      relation to the prevalence of different health risk behaviours among Czech
      adolescents (aged 15-16 years) based on cross-sectional study design. Risk
      behaviours such as cigarette smoking, alcohol drinking and marijuana use among
      adolescents have often been shown to co-occur with each other. Data from the
      European School Survey Project on Alcohol and Other Drugs 2007 were used. A total
      of 7616 students from the Czech Republic were analysed in the study. About two
      thirds of students (63.5%) did not engage in any type of considered health risk
      behaviour, 21.1% reported one risk, 10.8% two risks, and 4.6% three risks. Thus,
      in sum 15.4% of Czech, students were engaged in multiple risk behaviour forms.
      Separate multilevel logistic regression models were performed in order to explore
      the redistribution of factors on categories of multiple health risk behaviour. 

PMID- 24945103
TI  - Do minority and poor neighborhoods have higher access to fast-food restaurants in
      the United States?
AB  - BACKGROUND: Disproportionate access to unhealthy foods in poor or minority
      neighborhoods may be a primary determinant of obesity disparities. We
      investigated whether fast-food access varies by Census block group (CBG) percent
      black and poverty. METHODS: We measured the average driving distance from each
      CBG population-weighted centroid to the five closest top ten fast-food chains and
      CBG percent black and percent below poverty. RESULTS: Among 209,091 CBGs analyzed
      (95.1% of all US CBGs), CBG percent black was positively associated with fast
      food access controlling for population density and percent poverty (average
      distance to fast-food was 3.56 miles closer (95% CI: -3.64, -3.48) in CBGs with
      the highest versus lowest quartile of percentage of black residents). Poverty was
      not independently associated with fast-food access. The relationship between fast
      food access and race was stronger in CBGs with higher levels of poverty (p for
      interaction <0.0001). CONCLUSIONS: Predominantly black neighborhoods had higher
      access to fast-food while poverty was not an independent predictor of fast-food
      access.

PMID- 24945102
TI  - Causes and Consequences of Age-Related Changes in DNA Methylation: A Role for
      ROS?
AB  - Recent genome-wide analysis of C-phosphate-G (CpG) sites has shown that the DNA
      methylome changes with increasing age, giving rise to genome-wide hypomethylation
      with site-specific incidences of hypermethylation. This notion has received a lot
      of attention, as it potentially explains why aged organisms generally have a
      higher risk of age-related diseases. However, very little is known about the
      mechanisms that could cause the occurrence of these changes. Moreover, there does
      not appear to be a clear link between popular theories of aging and alterations
      in the methylome. Some of the most fruitful of these theories attribute an
      important role to reactive oxygen species, which seem to be responsible for an
      increase in oxidative damage to macromolecules, such as DNA, during the lifetime
      of an organism. In this review, the connection between changes in DNA methylation
      and these reactive oxygen species is discussed, as well as the effect of these
      changes on health. Deeper insights into the nature, causes and consequences of
      the aging methylome might provide a deeper understanding of the molecular
      mechanisms of aging and eventually contribute to the development of new
      diagnostic and therapeutic tools. 

PMID- 24945105
TI  - Validity of beta-D-glucosidase activity measured in dried blood samples for
      detection of potential Gaucher disease patients.
AB  - OBJECTIVES: Gaucher disease (GD) diagnosis relies on the demonstration of
      deficient beta-D-glucosidase (GBA) activity in cellular homogenates. Diagnosis
      process, however, can be delayed as (i) some GD symptoms are non-specific; and
      (ii) diagnostic tests are performed in specialized laboratories. These
      difficulties negatively impact on timely access of patients to therapy. GBA assay
      in dried blood spots (DBS) represents a method facilitating early identification
      of patients who will be finally diagnosed with gold standard assay of nucleated
      cells. Aim of this study is to investigate the DBS analytical performance
      compared with gold standard method. DESIGN & METHODS: A cross-sectional study
      started by comparing data of 50 DBS and 50 homogenate samples from the same
      subjects (25 known-GD and 25 controls). The subsequent phase examined 443 DBS
      samples. Along with these, 73 blood samples were sent for leukocyte separation
      and/or EBV-lymphoblast cell lines, and 1 skin biopsy for fibroblast cell lines.
      Overall the study included a total of 493 subjects. RESULTS: While the results
      from this first validation group did not yield false positive/negative values,
      when the analysis was extended to 443 DBS, 14.4% (64 samples) of positive results
      was yielded. Among these, only 15 were confirmed as GD values with gold standard
      test. In addition, a thorough examination of some clinical data also revealed 2
      false negative results which were confirmed by both enzymatic and molecular
      analyses. CONCLUSIONS: DBS test could be useful as screening method although with
      cautions, whereas the standardized GBA assay should remain the gold standard for
      laboratory diagnosis of Gaucher disease.

PMID- 24945108
TI  - Progressive acylation of pyrene engineers solid state packing and colour via C
      H...H-C, C-H...O and pi-pi interactions.
AB  - Quantum theory of atoms-in-molecules and Hirshfeld surface analyses indicated an
      increase in the extent of (i) C-H...H-C; (ii) C-H...O, (iii) pi-pi interactions
      and a decrease in the extent of (i) sigma-pi interaction, (ii) an interplanar
      angle between the vicinal pyrene units in a series of acetylpyrene derivatives
      offering blue-green-orange emissive crystals.

PMID- 24945107
TI  - Taenia saginata taeniosis: copro-antigen time-course in a voluntary self
      infection.
AB  - Human taeniosis due to Taenia saginata is cosmopolitan where beef is consumed;
      however, there is little or no information on the symptomatology over the early
      time-course of human infection. Copro-antigen detection is very useful in
      community screening for human taeniosis, particularly for T. solium, but there
      are no data on copro-antigen detection in pre-patent infection. In order to
      provide insight into this, a voluntary self-infection with T. saginata was
      undertaken and monitored over a 6-month period using a copro-antigen enzyme
      linked immunosorbent assay (ELISA) that we developed using anti-T. saginata
      antibody based reagents. Tapeworm patency, defined as first proglottid
      appearance, occurred on day 86 post-infection (pi) and was followed by almost
      daily release of proglottids (range 1-8) until termination using praziquantel on
      day 180 pi. The first 10 weeks post-infection (wpi) were essentially
      asymptomatic, followed by main symptoms of involuntary proglottid discharge
      throughout the infection period, and abdominal discomfort peaking around 15-19
      wpi. Copro-antigens could not be reliably detected until 2 weeks before
      proglottid patency but then remained highly elevated over the next 15 weeks until
      treatment. Copro-antigen levels reverted to negative 4 days post-treatment. This
      time-course study suggests that although copro-antigen ELISA is an excellent
      diagnostic tool for established patent infections of T. saginata, it may not be
      reliable for faecal antigen detection in the early infection phase prior to
      proglottid release for T. saginata and other human taenioses. 

PMID- 24945109
TI  - Selective androgen receptor modulators as improved androgen therapy for advanced
      breast cancer.
AB  - Androgens were at one time a therapeutic mainstay in the treatment of advanced
      breast cancer. Despite comparable efficacy, SERMs and aromatase inhibitors
      eventually became the therapies of choice due to in part to preferred side-effect
      profiles. Molecular characterization of breast tumors has revealed an abundance
      of androgen receptor expression but the choice of an appropriate androgen
      receptor ligand (agonist or antagonist) has been confounded by multiple
      conflicting reports concerning the role of the receptor in the disease. Modern
      clinical efforts have almost exclusively utilized antagonists. However, the
      recent clinical development of selective androgen receptor modulators with
      greatly improved side-effect profiles has renewed interest in androgen agonist
      therapy for advanced breast cancer. 

PMID- 24945106
TI  - Top-down mass spectrometry of cardiac myofilament proteins in health and disease.
AB  - Myofilaments are composed of thin and thick filaments that coordinate with each
      other to regulate muscle contraction and relaxation. PTMs together with genetic
      variations and alternative splicing of the myofilament proteins play essential
      roles in regulating cardiac contractility in health and disease. Therefore, a
      comprehensive characterization of the myofilament proteins in physiological and
      pathological conditions is essential for better understanding the molecular basis
      of cardiac function and dysfunction. Due to the vast complexity and dynamic
      nature of proteins, it is challenging to obtain a holistic view of myofilament
      protein modifications. In recent years, top-down MS has emerged as a powerful
      approach to study isoform composition and PTMs of proteins owing to its advantage
      of complete sequence coverage and its ability to identify PTMs and sequence
      variants without a priori knowledge. In this review, we will discuss the
      application of top-down MS to the study of cardiac myofilaments and highlight the
      insights it provides into the understanding of molecular mechanisms in
      contractile dysfunction of heart failure. Particularly, recent results of cardiac
      troponin and tropomyosin modifications will be elaborated. The limitations and
      perspectives on the use of top-down MS for myofilament protein characterization
      will also be briefly discussed.

PMID- 24945110
TI  - Regional specific regulation of steroid receptor coactivator-1 immunoreactivity
      by orchidectomy in the brain of adult male mice.
AB  - Androgens including testosterone and dihydrotestosterone play important roles on
      brain structure and function, either directly through androgen receptor or
      indirectly through estrogen receptors, which need coactivators for their
      transcription activation. Steroid receptor coactivator-1 (SRC-1) has been shown
      to be multifunctional potentials in the brain, but how it is regulated by
      androgens in the brain remains unclear. In this study, we explored the effect of
      orchidectomy (ORX) on the expression of SRC-1 in the adult male mice using nickel
      intensified immunohistochemistry. The results showed that ORX induced dramatic
      decrease of SRC-1 immunoreactivity in the olfactory tubercle, piriform cortex,
      ventral pallidum, most parts of the septal area, hippocampus, substantia nigra
      (compact part), pontine nuclei and nucleus of the trapezoid body (p<0.01).
      Significant decrease of SRC-1 was noticed in the dorsal and lateral septal
      nucleus, medial preoptical area, dorsomedial and ventromedial hypothalamic
      nucleus and superior paraolivary nucleus (p<0.05). Whereas in other regions
      examined, levels of SRC-1 immunoreactivity were not obviously changed by ORX
      (p>0.05). The above results demonstrated ORX downregulation of SRC-1 in specific
      regions that have been involved in sense of smell, learning and memory,
      cognition, neuroendocrine, reproduction and motor control, indicating that SRC-1
      play pivotal role in the mediating circulating androgenic regulation on these
      important brain functions. It also indicates that SRC-1 may serve as a novel
      target for the central disorders caused by the age-related decrease of
      circulating androgens. 

PMID- 24945111
TI  - Nuclear receptor modulation--role of coregulators in selective estrogen receptor
      modulator (SERM) actions.
AB  - Selective estrogen receptor modulators (SERMs) are a class of small-molecule
      chemical compounds that bind to estrogen receptor (ER) ligand binding domain
      (LBD) with high affinity and selectively modulate ER transcriptional activity in
      a cell- and tissue-dependent manner. The prototype of SERMs is tamoxifen, which
      has agonist activity in bone, but has antagonist activity in breast. Tamoxifen
      can reduce the risk of breast cancer and, at same time, prevent osteoporosis in
      postmenopausal women. Tamoxifen is widely prescribed for treatment and prevention
      of breast cancer. Mechanistically the activity of SERMs is determined by the
      selective recruitment of coactivators and corepressors in different cell types
      and tissues. Therefore, understanding the coregulator function is the key to
      understanding the tissue selective activity of SERMs. 

PMID- 24945113
TI  - Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a
      prospective controlled clinical study.
AB  - Alterations in lipid pattern and increased risk for obstetric/neonatal
      complications have been observed in patients with polycystic ovary syndrome
      (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and
      alterations in lipid profile have been related with adverse pregnancy outcomes.
      Based on these considerations, the aim of the present prospective controlled
      clinical study was to test the hypothesis that the changes in the lipid profile
      in patients with PCOS during pregnancy are characteristic and potentially related
      to the increased risk of obstetric/neonatal complications. One hundred and fifty
      nonobese PCOS women and 150 age- and body mass index (BMI)-matched healthy
      controls were enrolled. Serum lipids, glucose, insulin, and androgens levels were
      serially assayed in all subjects before and throughout pregnancy. Serum low
      density lipoprotein (LDL) and triglyceride (TG) concentrations were significantly
      (P<0.05) higher in PCOS group than in healthy controls at each assessment.
      Throughout pregnancy, serum LDL and TG levels increased significantly (P<0.05) in
      both groups, although the change from pre-pregnancy values was significantly
      (P<0.05) greater in PCOS patients than in healthy controls. A significant
      (P<0.05) relationship was observed between serum LDL and TG changes and changes
      in both insulin sensitivity indexes and androgen levels in PCOS patients alone.
      After adjusting for maternal age, pre-pregnancy BMI and lipid levels, body weight
      gain, and insulin-resistance markers, serum TG concentrations during pregnancy
      were directly and independently associated with obstetric complications in both
      groups, whereas serum LDL levels only in PCOS patients. We can conclude that
      nonobese PCOS patients had specific changes in lipid profile during pregnancy,
      and that the lipid pattern typical of PCOS may account for the more frequent
      adverse pregnancy outcomes. PCOS-related hormonal and metabolic features, such as
      insulin resistance and high androgen levels, may mediate this phenomenon. 

PMID- 24945114
TI  - Highly intense upconversion luminescence in Yb/Er:NaGdF4@NaYF4 core-shell
      nanocrystals with complete shell enclosure of the core.
AB  - The purpose of the present work is to demonstrate that the hexagonal Yb/Er:NaGdF4
      core size has a great impact on the completeness of the NaYF4 shell covering the
      core. With the increase of core size, the morphology of core-shell nanocrystals
      evolves from nanosphere to hexagonal nanoprism and finally to hexagonal nanoplate
      and, impressively, compared to that on the lateral faces of cores, the shell
      thickness on the top/bottom faces of cores becomes thinner. The shell growth
      mechanism is proposed to be the separate nucleation of the shell precursors
      followed by their ripening-mediated deposition on the cores. Based on this
      mechanism, controlling the thickness and completeness of the shell on the core
      can be easily realized by adopting appropriate size cores, which results in the
      intensification of upconversion luminescence of core-shell nanocrystals 10 000
      times as high as that of the core-only ones. Generally, these new findings should
      be beneficial for designing and fabricating complex core-shell architecture and
      the understanding of structure-related properties of core-shell nanocrystals. 

PMID- 24945112
TI  - Plasma non-esterified fatty acid levels in children and their relationship with
      sex steroids.
AB  - OBJECTIVE: Puberty is associated with decreased insulin sensitivity. Sexual
      hormones have been related with the onset of insulin resistance, but their
      relationship with non-esterified fatty acids (NEFA) remains unexplored. The aim
      of this study was to evaluate circulating NEFA levels in population-based samples
      of prepubertal children and adolescents and to analyze the association of NEFA
      with obesity, insulin resistance, and sexual hormones in adolescents.
      EXPERIMENTAL: The studied population included 854 randomly selected 6-8-year-old
      children and 822 children aged 12-16years. NEFA levels were determined using a
      commercial kit. Testosterone and estradiol levels were determined by RIA, and
      insulin and sex hormone binding protein by IRMA. HOMA was calculated as an
      indicator of insulin resistance. RESULTS: NEFA levels were lower in adolescents
      than in 6-8-year-old children, and decreased progressively with age between 12
      year-olds and 16-year-olds. No significant differences in NEFA levels were
      observed between obese and non-obese adolescents. NEFA were not correlated with
      insulin or HOMA in 12-16-year-old girls, and appear negatively correlated with
      these variables in boys. Insulin and HOMA were negatively correlated with SHBG
      levels in both sexes adjusting by age but NEFA levels were not. CONCLUSIONS: NEFA
      levels decrease with age in adolescents and are not significantly increased in
      obese children, supporting the fact that the decreased insulin sensitivity at
      this age is not affecting NEFA metabolism. Although SHBG is related to insulin
      and HOMA independently of age in both sexes, SHBG levels are not associated with
      NEFA.

PMID- 24945115
TI  - Psychological trajectories after intraoperative awareness with explicit recall.

PMID- 24945116
TI  - Paging doctor, emergency?

PMID- 24945117
TI  - Improving safety during sedation by nonanesthesiologists: do we lead or follow?

PMID- 24945118
TI  - How will we ever know if our machine is adequately flushed?

PMID- 24945119
TI  - Development of a novel blood-sparing agent in cardiac surgery: do we need another
      agent?

PMID- 24945120
TI  - Inferior vena cava obstruction after total artificial heart implantation.

PMID- 24945121
TI  - Subaortic membrane and the "unsimplified" Bernoulli equation.

PMID- 24945122
TI  - Infective endocarditis: the importance of intraoperative transesophageal
      echocardiography.

PMID- 24945123
TI  - Long-term psychosocial outcomes after intraoperative awareness with recall.
AB  - BACKGROUND: Posttraumatic stress disorder, a common psychiatric disorder in the
      general population, may follow a traumatic experience of awareness with recall
      during general anesthesia. METHODS: We conducted a matched cohort design with 9
      subjects after intraoperative awareness with recall during general anesthesia. A
      psychiatric diagnostic interview and questionnaire were performed on 9 matched
      controls and 9 subjects, a median of 17.2 years from their documented awareness
      episode. The subjects and the matched controls completed a battery of
      questionnaires related to psychosocial well-being, after which they participated
      in a diagnostic Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition Axis I Disorders. RESULTS: Patients
      with awareness did not seem to differ from their matched controls in subsequent
      psychosocial outcome, psychiatric morbidity, or quality of life. CONCLUSIONS: We
      found no indication that intraoperative awareness with recall had any deleterious
      long-term effects on patients' psychosocial outcome.

PMID- 24945124
TI  - Wake Up Safe and root cause analysis: quality improvement in pediatric
      anesthesia.
AB  - In 2006, the Quality and Safety Committee of the Society for Pediatric Anesthesia
      initiated a quality improvement project for the specialty of pediatric
      anesthesiology that ultimately resulted in the development of Wake Up Safe (WUS),
      a patient safety organization that maintains a registry of de-identified, serious
      adverse events. The ultimate goal of WUS is to implement change in processes of
      care that improve the quality and safety of anesthetic care provided to pediatric
      patients nationwide. Member institutions of WUS submit data regarding the types
      and numbers of anesthetics performed and information pertaining to serious
      adverse events. Before a member institution submits data for any serious adverse
      event, 3 anesthesiologists who were not involved in the event must analyze the
      event with a root cause analysis (RCA) to identify the causal factor(s). Because
      institutions across the country use many different RCA methods, WUS educated its
      members on RCA methods in an effort to standardize the analysis and evaluate each
      serious adverse event that is submitted. In this review, we summarize the
      background and development of this patient safety initiative, describe the
      standardized RCA method used by its members, demonstrate the use of this RCA
      method to analyze a serious event that was reported, and discuss the ways WUS
      plans to use the data to promote safer anesthetic practices for children. 

PMID- 24945125
TI  - Case discussion and root cause analysis: bupivacaine overdose in an infant
      leading to ventricular tachycardia.
AB  - An otherwise healthy 11-month-old, 8-kg infant presented for an elective
      circumcision. After a penile block with an excessive dose of 0.5% bupivacaine,
      the patient progressed to ventricular tachycardia. He was resuscitated with
      intralipid and had an uneventful recovery. The case was classified as a serious
      safety event, and a team was created to perform a root cause analysis. A sequence
      of events was constructed from gathered data, and policies and procedures were
      reviewed. Proximate cause was determined to be the failure of the surgeon,
      anesthesiologist, nurse, and scrub technician to communicate about the maximum
      dose of local anesthetic allowed before the medication being drawn up.
      Interventions were developed to target the proximate and contributing causes. 

PMID- 24945127
TI  - Topical and peripheral ketamine as an analgesic.
AB  - Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain
      settings, an action largely attributed to block of N-methyl-D-aspartate receptors
      in the spinal cord and inhibition of central sensitization processes. N-methyl-D
      aspartate receptors also are located peripherally on sensory afferent nerve
      endings, and this provided the initial impetus for exploring peripheral
      applications of ketamine. Ketamine also produces several other pharmacological
      actions (block of ion channels and receptors, modulation of transporters, anti
      inflammatory effects), and while these may require higher concentrations, after
      topical (e.g., as gels, creams) and peripheral application (e.g., localized
      injections), local tissue concentrations are higher than those after systemic
      administration and can engage lower affinity mechanisms. Peripheral
      administration of ketamine by localized injection produced some alterations in
      sensory thresholds in experimental trials in volunteers and in complex regional
      pain syndrome subjects in experimental settings, but many variables were
      unaltered. There are several case reports of analgesia after topical application
      of ketamine given alone in neuropathic pain, but controlled trials have not
      confirmed such effects. A combination of topical ketamine with several other
      agents produced pain relief in case, and case series, reports with response rates
      of 40% to 75% in retrospective analyses. In controlled trials of neuropathic pain
      with topical ketamine combinations, there were improvements in some outcomes, but
      optimal dosing and drug combinations were not clear. Given orally (as a gargle,
      throat swab, localized peritonsillar injections), ketamine produced significant
      oral/throat analgesia in controlled trials in postoperative settings. Topical
      analgesics are likely more effective in particular conditions (patient factors,
      disease factors), and future trials of topical ketamine should include a
      consideration of factors that could predispose to favorable outcomes. 

PMID- 24945126
TI  - Wrong site frenulectomy in a child: a serious safety event.
AB  - Wrong site surgery is a serious safety event that can result in temporary or even
      permanent harm. Various safety checklists and procedures have been added to our
      standard work in the operating room, but errors still get through our safety nets
      and patients are harmed. In this case report, we describe a wrong site
      frenulectomy in a child and discuss the root cause analysis of this error and
      also SMART (specific, measurable, achievable, realistic, timed) preventative
      actions that could be put into place to prevent a recurrence. 

PMID- 24945128
TI  - Computer-assisted personalized sedation: friend or foe?

PMID- 24945129
TI  - Management of venous air embolism.

PMID- 24945130
TI  - In response.

PMID- 24945131
TI  - The safe use of an airway exchange catheter.

PMID- 24945132
TI  - In response.

PMID- 24945133
TI  - A word of caution: dexmedetomidine and pulmonary hypertension.

PMID- 24945134
TI  - In response.

PMID- 24945135
TI  - Antioxidant, antimicrobial and neutrophil-modulating activities of herb extracts.
AB  - The present study provides a comprehensive data on the antioxidant, antimicrobial
      and neutrophil-modulating activities of extracts from six medicinal plants-
      blackberry (Rubus fruticosus) leaves, chokeberry (Aronia melanocarpa) leaves,
      hawthorn (Crataegus monogyna) leaves, lady's mantle (Alchemilla glabra) aerial
      parts, meadowsweet (Filipendula ulmaria) aerial parts and raspberry (Rubus
      idaeus) leaves. In order to analyze the antioxidant activity of the herbs,
      several methods (ORAC, TRAP, HORAC and inhibition of lipid peroxidation) were
      used. Blackberry leaves and meadowsweet extracts revealed the highest antioxidant
      activities via all methods. All extracts studied blocked almost completely the
      opsonized zymosan particle-activated ROS production by neutrophils from human
      whole blood. On the other hand, the effect of extracts on phorbol myristate
      acetate-activated ROS production was much milder and even nonsignificant in the
      case of chokeberry leaves. This latter result suggests that extracts (apart from
      their antioxidative activity) interfere with the signaling cascade of phagocyte
      activation upstream of the protein kinase C activation. The antimicrobial
      activity of the investigated extracts against 11 human pathogens was investigated
      using three different methods. Meadowsweet and blackberry leaves extracts had the
      highest antimicrobial effect and the lowest minimal inhibiting concentrations
      (MICs) against the microorganisms tested.

PMID- 24945136
TI  - The use of a one-step PCR method for the identification of Microsporum canis and
      Trichophyton mentagrophytes infection of pets.
AB  - INTRODUCTION: Dermatophytes are a closely related group of keratinophilic fungi.
      They encompass important etiological agents of superficial fungal infections.
      These fungi are able to invade keratinized tissues of humans and animals, causing
      dermatophytosis (ringworm) of hair, nails or skin. THE AIM: Traditional
      diagnostics of ringworm is based on morphological identification of cultured
      fungi and is time-consuming. MATERIALS AND METHODS: In this study, we applied a
      method patented by Brillowska-Dabrowska and coworkers (Brillowska-Dabrowska A,
      Saunte DM, Arenderup MC, 2007, Five-hour diagnosis of dermatophyte nail
      infections with specific detection of Trichophyton rubrum. J Clin Microbiol 45:
      1200-1204) which involves extraction of fungal DNA and PCR amplification with pan
      dermatophyte primers to confirm the presence of dermatophytes. RESULTS: The
      method used here is able to confirm the presence of dermatophyte DNA in pure
      cultures in less than 5 hours.

PMID- 24945137
TI  - Secondary malignancies in pediatric cancer survivors: perspectives and review of
      the literature.
AB  - With continuing improvements in the successful treatment of pediatric
      malignancies, long term survivors of pediatric cancers and their providers are
      faced with new oncologic issues regarding long-term morbidities. As pediatric
      cancer survivors have matured into adulthood, the development of secondary
      malignancies has become a significant issue for these patients. Whether a
      consequence of treatment for the patient's original cancer, such as chemotherapy,
      ionizing radiation, or hematopoietic stem cell transplantation, secondary
      malignancies now present patients and providers with new challenges regarding
      treatment, surveillance and counseling. We review the major risk factors for
      secondary malignancies in pediatric cancer survivors, with particular emphasis on
      important molecular and cytogenetic risk factors, both inherited and acquired. We
      conclude with a discussion of recommendations for surveillance and counseling of
      these patients. 

PMID- 24945138
TI  - Utilization of microfluidic V-junction device to prepare surface itraconazole
      adsorbed nanospheres.
AB  - Itraconazole is widely used as an anti-fungal drug to treat infections. However,
      its poor aqueous solubility results in low bioavailability. The aim of the
      present study was to improve the drug release profile by preparing surface
      itraconazole adsorbed polymethylsilsesquioxane (PMSQ) nanospheres using a V
      junction microfluidic (VJM) device. In order to generate nanospheres with rough
      surface, the process flow rate of perfluorohexane (PFH) was set between 50 and
      300 MUl min(-1) while the flow rate of PMSQ and itraconazole solution were
      constant at 300 MUl min(-1). Variations in the PFH flow rate enable the
      controlled size generation of nanospheres. PMSQ nanospheres adsorbing
      itraconazole were characterized by SEM, FTIR and Zetasizer. The release of
      itraconazole from PMSQ nanosphere surface was measured using UV spectroscopy.
      Nanosphere formulations with a range of sphere size (120, 320 and 800 nm
      diameter) were generated and drug release was studied. 120 nm itraconazole coated
      PMSQ nanospheres were found to present highest drug encapsulation efficiency and
      13% drug loading in a more reproducible manner compared to 320 nm and 800 nm
      sized nanosphere formulations. Moreover, 120 nm itraconazole coated PMSQ
      nanospheres (encapsulation efficiency: 88%) showed higher encapsulation
      efficiency compared to 320 nm (encapsulation efficiency: 74%) and 800 nm
      (encapsulation efficiency: 62%) sized nanosphere formulations. The itraconazole
      coated PMSQ nanospheres were prepared continuously at the rate of 2.6 * 10(6) per
      minute via VJM device. Overall the VJM device enabled the preparation of
      monodisperse surface itraconazole adsorbed nanospheres with controlled in vitro
      drug release profile.

PMID- 24945139
TI  - A continuous flow method for estimation of drug release rates from emulsion
      formulations.
AB  - We present a continuous-flow method that allows the release of drugs from
      submicron colloidal carriers to be estimated on a millisecond timescale. The
      technique is applied to the study of release of a model drug (tetracaine) from
      lipid emulsions, and shows that the solute drug is released in this timescale,
      and thus is primarily controlled by the rapid diffusion of the drug within the
      oil droplet. This confirms our previous claims that existing methods, such as
      dialysis or centrifugation, are too slow to provide useful release data for drug
      containing emulsions, and demonstrates that it is unlikely that a simple emulsion
      could be used as a circulating sustained-release formulation, as has been
      suggested by some workers. 

PMID- 24945140
TI  - Reconstruction of mandibular defects using the scapular tip free flap.
AB  - PURPOSE: Purpose of the article is to present the use of the scapular tip free
      flap (STFF) for the reconstruction of oromandibular defects. PATIENTS: Eleven
      patients who underwent oromandibular reconstruction with STFF were
      retrospectively evaluated with regards to form and function assessing mouth
      opening, dietary intake, and cosmetic outcome. Donor site morbidity was evaluated
      using the Constant-Murley test for the shoulder unit. RESULTS: Follow-up ranged
      from 6 to 35 months (mean 20.6 months). Good or excellent results in mouth
      opening and cosmesis were achieved in eight patients, speech was assessed as
      intelligible or normal in all but one patient and mean ambulation time after
      surgery was 2.5 days. Results of Constant score ranged from 45 to 70 (mean 60.6),
      and the main limitation encountered was elevation of the arm above the head,
      which was seen in all but one patient confirming the low impact of the technique
      on the shoulder system. CONCLUSION: Low morbidity, early ambulation time,
      possibility of simultaneous harvesting with the tumor resection, large
      musculocutaneous paddles in the chimeric version of the flap are advantages of
      the STFF and makes it a good choice in elderly patients, when other bone
      containing free flaps are not indicated because of the related morbidity, when
      other flaps are not available or when wide composite defects are approached.

PMID- 24945142
TI  - On the origins of suboptimality in human probabilistic inference.
AB  - Humans have been shown to combine noisy sensory information with previous
      experience (priors), in qualitative and sometimes quantitative agreement with the
      statistically-optimal predictions of Bayesian integration. However, when the
      prior distribution becomes more complex than a simple Gaussian, such as skewed or
      bimodal, training takes much longer and performance appears suboptimal. It is
      unclear whether such suboptimality arises from an imprecise internal
      representation of the complex prior, or from additional constraints in performing
      probabilistic computations on complex distributions, even when accurately
      represented. Here we probe the sources of suboptimality in probabilistic
      inference using a novel estimation task in which subjects are exposed to an
      explicitly provided distribution, thereby removing the need to remember the
      prior. Subjects had to estimate the location of a target given a noisy cue and a
      visual representation of the prior probability density over locations, which
      changed on each trial. Different classes of priors were examined (Gaussian,
      unimodal, bimodal). Subjects' performance was in qualitative agreement with the
      predictions of Bayesian Decision Theory although generally suboptimal. The degree
      of suboptimality was modulated by statistical features of the priors but was
      largely independent of the class of the prior and level of noise in the cue,
      suggesting that suboptimality in dealing with complex statistical features, such
      as bimodality, may be due to a problem of acquiring the priors rather than
      computing with them. We performed a factorial model comparison across a large set
      of Bayesian observer models to identify additional sources of noise and
      suboptimality. Our analysis rejects several models of stochastic behavior,
      including probability matching and sample-averaging strategies. Instead we show
      that subjects' response variability was mainly driven by a combination of a noisy
      estimation of the parameters of the priors, and by variability in the decision
      process, which we represent as a noisy or stochastic posterior. 

PMID- 24945141
TI  - Recombination in enteroviruses is a biphasic replicative process involving the
      generation of greater-than genome length 'imprecise' intermediates.
AB  - Recombination in enteroviruses provides an evolutionary mechanism for acquiring
      extensive regions of novel sequence, is suggested to have a role in genotype
      diversity and is known to have been key to the emergence of novel neuropathogenic
      variants of poliovirus. Despite the importance of this evolutionary mechanism,
      the recombination process remains relatively poorly understood. We investigated
      heterologous recombination using a novel reverse genetic approach that resulted
      in the isolation of intermediate chimeric intertypic polioviruses bearing genomes
      with extensive duplicated sequences at the recombination junction. Serial passage
      of viruses exhibiting such imprecise junctions yielded progeny with increased
      fitness which had lost the duplicated sequences. Mutations or inhibitors that
      changed polymerase fidelity or the coalescence of replication complexes markedly
      altered the yield of recombinants (but did not influence non-replicative
      recombination) indicating both that the process is replicative and that it may be
      possible to enhance or reduce recombination-mediated viral evolution if required.
      We propose that extant recombinants result from a biphasic process in which an
      initial recombination event is followed by a process of resolution, deleting
      extraneous sequences and optimizing viral fitness. This process has implications
      for our wider understanding of 'evolution by duplication' in the positive-strand
      RNA viruses. 

PMID- 24945144
TI  - Elimination of young erythrocytes from blood circulation and altered
      erythropoietic patterns during paraquat induced anemic phase in mice.
AB  - Paraquat a widely used herbicide causes a variety of toxic effects on humans and
      animals. The present study is focused on the interaction of paraquat with the
      mouse erythroid system. Administration of paraquat (10 mg/kg body weight i.p. on
      alternate days in C57Bl/6 mice) induced a significant fall in blood erythrocyte
      count on 7, 14, and 21 day time points but the erythrocyte count reverted back to
      normal by 28th day indicating the emergence of refractoriness to paraquat. A
      marked surge in the blood reticulocyte count was observed in paraquat treated
      mice that also subsided by 28th day. Young erythrocytes in circulation were
      randomly eliminated from blood circulation in paraquat treated mice and a
      significant elevation in the level of reactive oxygen species (ROS) was also
      observed maximally the erythrocytes of this age group. Cells representing various
      stages of erythroid differentiation in bone marrow and spleen were identified and
      enumerated flow cytometrically based on their expression of Ter119 and
      transferrin (CD71) receptor. Proliferative activity of erythroid cells, their
      relative proportion as well as their absolute numbers fell significantly in bone
      marrow of paraquat treated mice but all these parameters were significantly
      elevated in spleens of paraquat treated mice. These changes were essentially
      restricted to the cells belonging to the two earliest stages of erythroid
      differentiation. Taken together our results indicate that paraquat treatment
      causes a transient anemia in mice resulting from random elimination of young
      circulating erythrocytes as well as depressed erythropoietic activity in bone
      marrow. Spleen erythropoietic activity however was elevated in paraquat treated
      mice. 

PMID- 24945143
TI  - Multimeric assembly of host-pathogen adhesion complexes involved in apicomplexan
      invasion.

PMID- 24945145
TI  - Association of circulating C1q/TNF-related protein 1 levels with coronary artery
      disease in men.
AB  - OBJECTIVE: Obesity is a major risk factor for cardiovascular disease. Recent
      evidence demonstrates that dysregulation of fat-derived hormones, also known as
      adipokines, is linked with the pathogenesis of obesity-related disorders
      including coronary artery disease (CAD). Here, we investigated whether
      circulating level of an adipokine C1q/TNF-related protein (CTRP) 1 is associated
      with the prevalence of CAD. METHODS AND RESULTS: Consecutive 76 male CAD patients
      were enrolled from inpatients that underwent coronary angiography. Sixty four
      healthy male subjects served as controls. Plasma CTRP1 concentration was
      determined by enzyme-linked immunosorbent assay. CTRP1 levels were correlated
      positively with systolic blood pressure (BP) and triglyceride levels, and
      negatively with HDL cholesterol levels in all subjects. Plasma levels of CTRP1
      were significantly higher in CAD patients than in control subjects (CAD: 443.3+/
      18.6 ng/ml, control: 307.8+/-21.5 ng/ml, p<0.001). Multiple logistic regression
      analysis with body mass index, systolic BP, glucose, total cholesterol, HDL
      cholesterol, triglyceride, adiponectin and CTRP1 revealed that CTRP1 levels,
      together with systolic BP and HDL cholesterol, correlated with CAD. CONCLUSIONS:
      Our data indicate the close association of high CTRP1 levels with CAD prevalence,
      suggesting that CTRP1 represents a novel biomarker for CAD.

PMID- 24945146
TI  - Reconstituted human upper airway epithelium as 3-d in vitro model for nasal
      polyposis.
AB  - BACKGROUND: Primary human airway epithelial cells cultured in an air-liquid
      interface (ALI) develop a well-differentiated epithelium. However, neither
      characterization of mucociliar differentiation overtime nor the inflammatory
      function of reconstituted nasal polyp (NP) epithelia have been described.
      OBJECTIVES: 1st) To develop and characterize the mucociliar differentiation
      overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps
      (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP
      reconstituted epithelium maintains, compared to control nasal mucosa (NM), an
      inflammatory function. METHODS: Epithelial cells were obtained from 9 NP and 7
      control NM, and differentiated in ALI culture for 28 days. Mucociliary
      differentiation was characterized at different times (0, 7, 14, 21, and 28 days)
      using ultrastructure analysis by electron microscopy; DeltaNp63 (basal
      stem/progenitor cell), beta-tubulin IV (cilia), and MUC5AC (goblet cell)
      expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous
      (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days
      0, 14, and 28) through cytokine (IL-8, IL-1beta, IL-6, IL-10, TNF-alpha, and IL
      12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF)
      production was analysed by CBA (Cytometric Bead Array). RESULTS: In both NP and
      control NM ALI cultures, pseudostratified epithelium with ciliated, mucus
      secreting, and basal cells were observed by electron microscopy at days 14 and
      28. Displaying epithelial cell re-differentation, beta-tubulin IV and MUC5AC
      positive cells increased, while DeltaNp63 positive cells decreased overtime. No
      significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin
      secretions between both ALI cultures. IL-8 and GM-CSF were significantly
      increased in NP compared to control NM regenerated epithelia. CONCLUSION:
      Reconstituted epithelia from human NP epithelial cells cultured in ALI system
      provides a 3D in vitro model that could be useful both for studying the role of
      epithelium in CRSwNP while developing new therapeutic strategies, including cell
      therapy, for CRSwNP.

PMID- 24945147
TI  - Elevated plasma levels of the pituitary hormone Cthrc1 in individuals with red
      hair but not in patients with solid tumors.
AB  - BACKGROUND: An increasing number of studies report that Cthrc1 is expressed in
      various cancer cells. The present study sought to identify which cells in tumors
      and remodeling tissues express Cthrc1 and investigate the range of circulating
      human Cthrc1 levels in health and disease. METHODOLOGY/PRINCIPLE FINDINGS: Highly
      specific monoclonal antibodies were generated to detect Cthrc1 by ELISA in plasma
      and in tissues by immunohistochemistry. In human colon, gastric, breast,
      endometrial, pancreatic, kidney, lung and skin cancer, Cthrc1 was expressed by
      activated stromal cells and not the cancer cells themselves. Similarly,
      conditions evoking tissue remodeling, such as wound repair or angiotensin II
      mediated hypertension, induced Cthrc1 expression in interstitial and adventitial
      fibroblasts and perivascular stromal cells. Levels of Cthrc1 in plasma from
      healthy subjects were near the lower detection limit except for individuals with
      red hair, who had up to several hundred fold higher levels. Elevated Cthrc1 was
      also found in patients with diabetes, inflammatory conditions, and infections,
      but not solid tumors. Transgenic mouse studies suggested that Cthrc1 expression
      by stromal cells does not contribute to circulating levels. In human pituitaries,
      Cthrc1 was expressed in the anterior and intermediate lobes with unencapsulated
      Cthrc1 accumulations typically surrounded by chromophobe cells. CONCLUSIONS: We
      identify Cthrc1 as a marker for activated stromal cells. Cthrc1 is a pituitary
      hormone with significantly elevated levels in subjects carrying variant alleles
      of the melanocortin-1 receptor as wells as in patients with inflammatory
      conditions.

PMID- 24945149
TI  - Inflammation: gone with translation.

PMID- 24945148
TI  - Expression of multiple transgenes from a single construct using viral 2A peptides
      in Drosophila.
AB  - Expression of multiple reporter or effector transgenes in the same cell from a
      single construct is increasingly necessary in various experimental paradigms. The
      discovery of short, virus-derived peptide sequences that mediate a ribosome
      skipping event enables generation of multiple separate peptide products from one
      mRNA. Here we describe methods and vectors to facilitate easy production of
      polycistronic-like sequences utilizing these 2A peptides tailored for expression
      in Drosophila both in vitro and in vivo. We tested the separation efficiency of
      different viral 2A peptides in cultured Drosophila cells and in vivo and found
      that the 2A peptides from porcine teschovirus-1 (P2A) and Thosea asigna virus
      (T2A) worked best. To demonstrate the utility of this approach, we used the P2A
      peptide to co-express the red fluorescent protein tdTomato and the genetically
      encoded calcium indicator GCaMP5G in larval motorneurons. This technique enabled
      ratiometric calcium imaging with motion correction allowing us to record synaptic
      activity at the neuromuscular junction in an intact larval preparation through
      the cuticle. The tools presented here should greatly facilitate the generation of
      2A peptide-mediated expression of multiple transgenes in Drosophila. 

PMID- 24945150
TI  - Interaction of CPR5 with cell cycle regulators UVI4 and OSD1 in Arabidopsis.
AB  - The impact of cell cycle on plant immunity was indicated by the enhancement of
      disease resistance with overexpressing OSD1 and UVI4 genes that are negative
      regulators of cell cycle controller APC (anaphase promoting complex). CPR5 is
      another gene that is implicated in cell cycle regulation and plant immunity, but
      its mode of action is not known. Here we report the analysis of genetic
      requirement for the function of UVI4 and OSD1 in cell cycle progression control
      and in particular the involvement of CPR5 in this regulation. We show that the
      APC activator CCS52A1 partially mediates the function of OSD1 and UVI4 in female
      gametophyte development. We found that the cpr5 mutation suppresses the
      endoreduplication defect in the uvi4 single mutant and partially rescued the
      gametophyte development defect in the osd1 uvi4 double mutant while the uvi4
      mutation enhances the cpr5 defects in trichome branching and plant disease
      resistance. In addition, cyclin B1 genes CYCB1;1, CYCB1;2, and CYCB1;4 are
      upregulated in cpr5. Therefore, CPR5 has a large role in cell cycle regulation
      and this role has a complex interaction with that of UVI4 and OSD1. This study
      further indicates an intrinsic link between plant defense responses and cell
      cycle progression. 

PMID- 24945152
TI  - Oxidative damage and autophagy in the human trabecular meshwork as related with
      ageing.
AB  - Autophagy is an intracellular lysosomal degradation process induced under stress
      conditions. Autophagy also plays a major role in ocular patho-physiology.
      Molecular aging does occur in the trabecular meshwork, the main regulator of
      aqueous humor outflow, and trabecular meshwork senescence is accompanied by
      increased oxidative stress. However, the role of autophagy in trabecular meshwork
      patho-physiology has not yet been examined in vivo in human ocular tissues. The
      purpose of the herein presented study is to evaluate autophagy occurrence in ex
      vivo collected human trabecular meshwork specimens and to evaluate the
      relationship between autophagy, oxidative stress, and aging in this tissue. Fresh
      trabecular meshwork specimens were collected from 28 healthy corneal donors
      devoid of ocular pathologies and oxidative DNA damage, and LC3 and p62 protein
      expression analyzed. In a subset of 10 subjects, further to trabecular meshwork
      proteins, the amounts of cathepesin L and ubiquitin was analyzed by antibody
      microarray in aqueous humor. Obtained results demonstrate that autophagy
      activation, measured by LC3II/I ratio, is related with. oxidative damage
      occurrence during aging in human trabecular meshwork. The expression of autophagy
      marker p62 was lower in subjects older than 60 years as compared to younger
      subjects. These findings reflect the occurrence of an agedependent increase in
      the autophagy as occurring in the trabecular meshwork. Furthermore, we showed
      that aging promotes trabecular-meshwork senescence due to increased oxidative
      stress paralleled by autophagy increase. Indeed, both oxidative DNA damage and
      autophagy were more abundant in subjects older than 60 years. These findings shed
      new light on the role of oxidative damage and autophagy during trabecular
      meshwork aging. 

PMID- 24945154
TI  - Predicting potential global distributions of two Miscanthus grasses: implications
      for horticulture, biofuel production, and biological invasions.
AB  - In many regions, large proportions of the naturalized and invasive non-native
      floras were originally introduced deliberately by humans. Pest risk assessments
      are now used in many jurisdictions to regulate the importation of species and
      usually include an estimation of the potential distribution in the import area.
      Two species of Asian grass (Miscanthus sacchariflorus and M. sinensis) that were
      originally introduced to North America as ornamental plants have since escaped
      cultivation. These species and their hybrid offspring are now receiving attention
      for large-scale production as biofuel crops in North America and elsewhere. We
      evaluated their potential global climate suitability for cultivation and
      potential invasion using the niche model CLIMEX and evaluated the models'
      sensitivity to the parameter values. We then compared the sensitivity of
      projections of future climatically suitable area under two climate models and two
      emissions scenarios. The models indicate that the species have been introduced to
      most of the potential global climatically suitable areas in the northern but not
      the southern hemisphere. The more narrowly distributed species (M.
      sacchariflorus) is more sensitive to changes in model parameters, which could
      have implications for modelling species of conservation concern. Climate
      projections indicate likely contractions in potential range in the south, but
      expansions in the north, particularly in introduced areas where biomass
      production trials are under way. Climate sensitivity analysis shows that
      projections differ more between the selected climate change models than between
      the selected emissions scenarios. Local-scale assessments are required to overlay
      suitable habitat with climate projections to estimate areas of cultivation
      potential and invasion risk. 

PMID- 24945156
TI  - Novel method for analysis of allele specific expression in triploid Oryzias
      latipes reveals consistent pattern of allele exclusion.
AB  - Assessing allele-specific gene expression (ASE) on a large scale continues to be
      a technically challenging problem. Certain biological phenomena, such as X
      chromosome inactivation and parental imprinting, affect ASE most drastically by
      completely shutting down the expression of a whole set of alleles. Other more
      subtle effects on ASE are likely to be much more complex and dependent on the
      genetic environment and are perhaps more important to understand since they may
      be responsible for a significant amount of biological diversity. Tools to assess
      ASE in a diploid biological system are becoming more reliable. Non-diploid
      systems are, however, not uncommon. In humans full or partial polyploid states
      are regularly found in both healthy (meiotic cells, polynucleated cell types) and
      diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this
      work we have studied ASE in the medaka fish model system. We have developed a
      method for determining ASE in polyploid organisms from RNAseq data and we have
      implemented this method in a software tool set. As a biological model system we
      have used nuclear transplantation to experimentally produce artificial triploid
      medaka composed of three different haplomes. We measured ASE in RNA isolated from
      the livers of two adult, triploid medaka fish that showed a high degree of
      similarity. The majority of genes examined (82%) shared expression more or less
      evenly among the three alleles in both triploids. The rest of the genes (18%)
      displayed a wide range of ASE levels. Interestingly the majority of genes (78%)
      displayed generally consistent ASE levels in both triploid individuals. A large
      contingent of these genes had the same allele entirely suppressed in both
      triploids. When viewed in a chromosomal context, it is revealed that these genes
      are from large sections of 4 chromosomes and may be indicative of some broad
      scale suppression of gene expression. 

PMID- 24945158
TI  - Odynophagia, neck pain, and stiffness.

PMID- 24945157
TI  - Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production
      and uncoupling activity.
AB  - Although mitochondrial dysfunction is often accompanied by excessive reactive
      oxygen species (ROS) production, we previously showed that an increase in random
      somatic mtDNA mutations does not result in increased oxidative stress. Normal
      levels of ROS and oxidative stress could also be a result of an active
      compensatory mechanism such as a mild increase in proton leak. Uncoupling protein
      2 (UCP2) was proposed to play such a role in many physiological situations.
      However, we show that upregulation of UCP2 in mtDNA mutator mice is not
      associated with altered proton leak kinetics or ROS production, challenging the
      current view on the role of UCP2 in energy metabolism. Instead, our results argue
      that high UCP2 levels allow better utilization of fatty acid oxidation resulting
      in a beneficial effect on mitochondrial function in heart, postponing systemic
      lactic acidosis and resulting in longer lifespan in these mice. This study
      proposes a novel mechanism for an adaptive response to mitochondrial
      cardiomyopathy that links changes in metabolism to amelioration of respiratory
      chain deficiency and longer lifespan. 

PMID- 24945155
TI  - Identification and characterization of seminal fluid proteins in the Asian tiger
      mosquito, Aedes albopictus.
AB  - The Asian tiger mosquito (Aedes albopictus) is an important vector for pathogens
      that affect human health, including the viruses that cause dengue and Chikungunya
      fevers. It is also one of the world's fastest-spreading invasive species. For
      these reasons, it is crucial to identify strategies for controlling the
      reproduction and spread of this mosquito. During mating, seminal fluid proteins
      (Sfps) are transferred from male mosquitoes to females, and these Sfps modulate
      female behavior and physiology in ways that influence reproduction. Despite the
      importance of Sfps on female reproductive behavior in mosquitoes and other
      insects, the identity of Sfps in Ae. albopictus has not previously been reported.
      We used transcriptomics and proteomics to identify 198 Sfps in Ae. albopictus. We
      discuss possible functions of these Sfps in relation to Ae. albopictus
      reproduction-related biology. We additionally compare the sequences of these Sfps
      with proteins (including reported Sfps) in several other species, including Ae.
      aegypti. While only 72 (36.4%) of Ae. albopictus Sfps have putative orthologs in
      Ae. aegypti, suggesting low conservation of the complement of Sfps in these
      species, we find no evidence for an elevated rate of evolution or positive
      selection in the Sfps that are shared between the two Aedes species, suggesting
      high sequence conservation of those shared Sfps. Our results provide a foundation
      for future studies to investigate the roles of individual Sfps on feeding and
      reproduction in this mosquito. Functional analysis of these Sfps could inform
      strategies for managing the rate of pathogen transmission by Ae. albopictus. 

PMID- 24945160
TI  - An interactive-technology health behavior promotion program for heart failure
      patients: a pilot study of experiences and needs of patients and nurses in the
      hospital setting.
AB  - BACKGROUND: Heart failure (HF) is a chronic condition, prevalent especially among
      older people, characterized by acute episodes leading to hospitalization. To
      promote HF patients' engagement in physical activity (PA) and adherence to
      medication, we developed Motivate4Change: a new interactive, information and
      communication technology (ICT)-based health promotion program for delivery in the
      hospital. The development of this program was guided by the Intervention Mapping
      protocol for the planning of health promotion programs. The users of
      Motivate4Change were defined as hospitalized HF patients and hospital nurses
      involved in HF patient education. OBJECTIVE: Two aims were addressed. First, to
      explore the use of interactive technology in the hospital setting and second, to
      evaluate user needs in order to incorporate them in Motivate4Change. METHODS:
      Participant observations at a hospital in the United Kingdom and semistructured
      interviews were conducted with hospitalized HF patients and HF nurses following
      their completion of Motivate4Change. Interviews were recorded, transcribed, and
      analyzed according to a thematic coding approach. RESULTS: Seven patients and 3
      nurses completed Motivate4Change and were interviewed. Results demonstrated that
      patient needs included empathic and contextual content, interactive learning, and
      support from others, including nurses and family members. The nurse needs
      included integration in current educational practices and finding opportunities
      for provision of the program. CONCLUSIONS: The current work provides insight into
      user needs regarding an interactive-technology health promotion program for
      implementation in the hospital setting, such as Motivate4Change.

PMID- 24945159
TI  - Prediction of acute respiratory disease in current and former smokers with and
      without COPD.
AB  - BACKGROUND: The risk factors for acute episodes of respiratory disease in current
      and former smokers who do not have COPD are unknown. METHODS: Eight thousand two
      hundred forty-six non-Hispanic white and black current and former smokers in the
      Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU)
      every 6 months to determine acute respiratory episodes requiring antibiotics or
      systemic corticosteroids, an ED visit, or hospitalization. Negative binomial
      regression was used to determine the factors associated with acute respiratory
      episodes. A Cox proportional hazards model was used to determine adjusted hazard
      ratios (HRs) for time to first episode and an acute episode of respiratory
      disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658
      had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred
      three acute episodes of respiratory disease and 2,707 hospitalizations were
      reported in LFU (3,044 acute episodes of respiratory disease and 827
      hospitalizations in those without COPD). Major predictors included acute episodes
      of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24
      per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10%
      change in % predicted FEV1), and poor health-related quality of life (HR, 1.07;
      95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory
      Questionnaire score). Risks were similar for those with and without COPD.
      CONCLUSIONS: Although acute episode of respiratory disease rates are higher in
      subjects with COPD, risk factors are similar, and at a population level, there
      are more episodes in smokers without COPD.

PMID- 24945161
TI  - Revisiting early hypothyroidism screening in infants with Down syndrome.
AB  - OBJECTIVE: To identify if the incidence of hypothyroidism in infants with Down
      syndrome is higher than previous childhood estimates (15%) when examined prior to
      the standard retesting at 6 months of age. STUDY DESIGN: A retrospective
      observational cohort study of 122 children with Down syndrome admitted to a
      university-based birthing hospital between May 2000 and March 2012. Demographic
      data (for example, date of birth, gender, gestational age, inborn) and diagnostic
      data (Down syndrome, congenital heart disease and gastrointestinal disease) were
      cross-linked with thyroid hormone laboratory tests (total thyroxine, free
      thyroxine and thyroid stimulating hormone) to determine incidence of identified
      hypothyroidism and thyroid testing prior to 4 months of age (n=80). RESULT: In
      all, 32.5% were found to have any hypothyroidism. Of these, 14 were primary
      hypothyroidism (17.5%) needing supplemental T4 therapy, 12 were compensated
      hypothyroidism (15%) and euthyroid was identified in 54 infants (67.5%).
      CONCLUSION: Despite normal newborn screens, the incidence of any hypothyroidism
      (early compensated hypothyroidism and primary hypothyroidism) was higher than
      previously reported.

PMID- 24945163
TI  - Placental pathology and neonatal thrombocytopenia: lesion type is associated with
      increased risk.
AB  - OBJECTIVE: To investigate the association between thrombocytopenia and placental
      lesions. STUDY DESIGN: Cases included singleton infants admitted to the intensive
      care unit (2005 to 2010) with platelet counts <100 000 MUl(-1). We selected a
      contemporaneous control group matched for gestational age: 49 cases and 63
      controls. The frequency of thrombosis in fetal vessels, fetal thrombotic
      vasculopathy, acute chorioamnionitis, chronic villitis, infarcts, hematomas, cord
      insertion and increased circulating nucleated red blood cells were identified on
      retrospective review of placental histology. Logistic regression models were used
      to test for associations. RESULT: Placental lesions associated with poor maternal
      perfusion (odds ratio (OR) 3.36, 95% confidence interval (CI) 1.38, 8.15) or
      affecting fetal vasculature (OR 2.75, 95% CI 1.05, 7.23), but not inflammation,
      were associated with thrombocytopenia. A Pearson Chi-Square Test for Independence
      for fetal and maternal lesions indicated that the two are independent factors.
      CONCLUSION: Poor maternal perfusion and fetal vascular lesions are independently
      associated with thrombocytopenia in the newborn.

PMID- 24945164
TI  - The health effects of obesity.

PMID- 24945162
TI  - Do maternal opioids reduce neonatal regional brain volumes? A pilot study.
AB  - OBJECTIVE: A substantial number of children exposed to gestational opioids have
      neurodevelopmental, behavioral and cognitive problems. Opioids are not
      neuroteratogens but whether they affect the developing brain in more subtle ways
      (for example, volume loss) is unclear. We aimed to determine the feasibility of
      using magnetic resonance imaging (MRI) to assess volumetric changes in healthy
      opioid-exposed infants. STUDY DESIGN: Observational pilot cohort study conducted
      in two maternity hospitals in New South Wales, Australia. Maternal history and
      neonatal urine and meconium screens were obtained to confirm drug exposure.
      Volumetric analysis of MRI scans was performed with the ITK-snap program. RESULT:
      Scans for 16 infants (mean (s.d.) gestational age: 40.9 (1.5) weeks, birth
      weight: 3022.5 (476.6) g, head circumference (HC): 33.7 (1.5 cm)) were analyzed.
      Six (37.5%) infants had HC <25th percentile. Fourteen mothers used methadone,
      four used buprenorphine and 11 used more than one opioid (including heroin,
      seven). All scans were structurally normal whole brain volumes (357.4 (63.8)) and
      basal ganglia (14.5 (3.5)) ml were significantly smaller than population means
      (425.4 (4.8), 17.1 (4.4) ml, respectively) but lateral ventricular volumes (3.5
      (1.8) ml) were larger than population values (2.1(1.5)) ml. CONCLUSION: Our pilot
      study suggests that brain volumes of opioid-exposed babies may be smaller than
      population means and that specific regions, for example, basal ganglia, that are
      involved in neurotransmission, may be particularly affected. Larger studies
      including correlation with neurodevelopmental outcomes are warranted to
      substantiate this finding.

PMID- 24945165
TI  - Intake of key chronic disease-related nutrients among baby boomers.
AB  - OBJECTIVES: The dietary habits of baby boomers (people born between 1946 and
      1964) undoubtedly will have a substantial impact on their future health; however,
      dietary information regarding the intake of key chronic disease-related nutrients
      is lacking for this generation. The objective of this study was to compare the
      dietary intake of key chronic disease-related nutrients of the baby boomer
      generation with the previous generation of middle-aged adults. METHODS: National
      cross-sectional study comparison analyzing data from the National Health and
      Nutrition Examination Survey (NHANES) including NHANES III (1988-1994) and the
      NHANES for 2007-2010, focused on adult respondents ages 46 to 64 years who were
      not institutionalized at the time of each survey. The two cohorts were compared
      with regard to dietary intake of key nutritional components. The main outcome
      measures were intake of total calories, sodium, cholesterol, fat, fruits,
      vegetables, vitamin C, water, and fiber. RESULTS: The baby boomers' average daily
      intake of nutrients exceeded that of the previous generation of middle-aged
      adults for total calories (2118/1999), total fat (82/76 g), sodium (3513/3291
      mg), and cholesterol (294/262 g; all P < 0.001). The intake of vitamin C (105/89
      g), water (1208/1001 g), and vegetables (199/229 g) was less than that of the
      previous generation (P < 0.001), and the dietary intake of fruit and fiber was
      unchanged. In regression analyses, dietary changes remained significant after
      controlling for age, race, sex, and socioeconomic status (all P < 0.01).
      CONCLUSIONS: The study findings document higher dietary intake of key chronic
      disease-related nutrients along with reduced vegetable intake among baby boomers
      compared with the previous generation of middle-aged adults. These findings are
      indicative of a diet that may contribute to increased rates of chronic disease
      among individuals in this age group.

PMID- 24945167
TI  - Do physicians underrecognize obesity?
AB  - OBJECTIVES: A physician's advice is among the strongest predictors of efforts
      toward weight management made by obese patients, yet only a minority receives
      such advice. One contributor could be the physician's failure to recognize true
      obesity. The objectives of this study were to assess physicians' ability to
      recognize obesity and to identify factors associated with recognition and
      documentation of obesity. METHODS: Internal medicine residents and attending
      physicians at three academic urban primary care clinics and their adult patients
      participated in a study using recognition and documentation of patient obesity as
      the main measures. RESULTS: A total of 52 physicians completed weight assessments
      for 400 patients. The mean patient age was 51 years, 56% were women, 77% were
      Hispanic, and 67% had one or more obesity-related comorbidity. There were 192
      (48%) patients, of whom 66% were correctly identified by physicians as being
      obese, 86% of those with a body mass index (BMI) >= 35, but only 49% of those
      with a BMI of 30 to 34.9 (P < 0.0001). Fewer obese Hispanic patients were
      identified than were non-Hispanic patients (62% vs 76%; P = 0.03). No physician
      characteristics were significantly associated with recognition of obesity.
      Physicians documented obesity as a problem for 51% of patients. Attending
      physicians documented obesity more frequently than did residents (64% vs 43%,
      odds ratio 2.5, 95% confidence interval 1.3-4.6) and normal-weight physicians
      documented obesity more frequently than overweight physicians (58% vs 41%, odds
      ratio 2.0, 95% confidence interval 1.0-4.0). Documentation was more common for
      patients with a BMI >= 35 and for non-Hispanics. Documentation was not more
      common for patients with obesity-related comorbidities. CONCLUSIONS: Physicians
      have difficulty recognizing obesity unless patients' BMI is >= 35. Training
      physicians to recognize true obesity may increase rates of documentation, a first
      step toward treatment.

PMID- 24945168
TI  - Body mass index, mortality, and the obesity paradox in type 2 diabetes mellitus:
      the effect of hypertension.

PMID- 24945166
TI  - Self-reported versus actual weight and height data contribute to different weight
      misperception classifications.
AB  - OBJECTIVES: The purpose of the study was to examine potential differences between
      two approaches to defining adolescent weight misperception. Specifically, weight
      status perception was compared with self-reported weight status and actual weight
      status (based on body mass index percentiles calculated from self-reported and
      actual weights and heights, respectively). Furthermore, the accuracy of assigning
      weight status based on body mass index percentiles calculated from self-reported
      weights and heights was assessed by comparing them with actual weight status.
      METHODS: Data were extracted from Team Up for Healthy Living, an 8-week, school
      based obesity prevention program in southern Appalachia. Participants (N = 1509)
      were predominately white (93.4%) and ninth graders (89.5%), with approximately
      equivalent representation of both sexes (50.7% boys). RESULTS: The study revealed
      significant differences between the approaches to defining weight misperception
      (chi(2) = 16.2; P = 0.0003). CONCLUSIONS: Researchers should interpret study
      findings with awareness of potential differences based on the method of
      calculating weight misperception.

PMID- 24945169
TI  - Editor's response.

PMID- 24945170
TI  - Does melatonin have therapeutic use in tinnitus?
AB  - Melatonin, a hormone produced by the pineal gland, may be a promising treatment
      option for tinnitus. The primary functions of this hormone are believed to be the
      initiation and maintenance of sleep because its secretions coincide with
      circadian rhythms. Some investigators have noted that melatonin may alleviate
      subjective symptoms of tinnitus. Moreover, melatonin may have properties
      protective against ototoxic drugs such as amikacin, gentamicin, or cancer
      therapeutic agents that are dose dependent. In vitro, melatonin has demonstrated
      antioxidative properties and it has been postulated that these antioxidative
      properties contribute to the alleviation of tinnitus. Melatonin levels used to
      obtain these findings in vitro, however, are at supraphysiologic levels;
      therefore, it is more likely that the benefits from taking supplemental melatonin
      occur from minimal antioxidative properties, sleep enhancement, or other
      potential methods of action that are not yet understood. Melatonin offers minimal
      risk of toxicity with modest daily doses such as 1 to 3 mg, as well as a low cost
      and favorable adverse effect profile for older adults. In addition to potential
      benefits in the treatment of tinnitus, melatonin also may have beneficial
      neurogenerative properties. We recommend that melatonin be considered for use in
      patients with significant tinnitus. 

PMID- 24945171
TI  - Commentary on "does melatonin have therapeutic use in tinnitus?".

PMID- 24945172
TI  - Discrepancies in cardiovascular disease risk calculation affect aspirin use
      recommendations in patients with diabetes.
AB  - OBJECTIVES: Aspirin is recommended for cardiovascular disease (CVD) prevention in
      patients who are at high risk for CVD. The objective of this study was to compare
      agreement between two American Diabetes Association-endorsed CVD risk calculators
      in identifying candidates for aspirin therapy. METHODS: Adult patients with
      diabetes mellitus (n = 238) were studied for 1 year in a family medicine clinic.
      Risk scores were calculated based on the United Kingdom Prospective Diabetes
      Study Risk Engine and the Atherosclerosis Risk in Communities Coronary Heart
      Disease Risk Calculator. Analyses included chi(2), kappa scores, and logistic
      regressions. RESULTS: The Atherosclerosis Risk in Communities Coronary Heart
      Disease Risk Calculator identified 50.4% of patients as high risk versus 23.5% by
      the United Kingdom Prospective Diabetes Study Risk Engine. kappa score for
      agreement identifying high-risk status was 0.3642. Among patients at high risk,
      African Americans (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24-0.86)
      and those with uncontrolled diabetes (OR 0.30, 95% CI 0.16-0.56) had lower odds
      of disagreement, whereas nonsmokers had higher odds (OR 2.98, 95% CI 1.57-5.69).
      Among patients at low risk, women (OR 3.83, 95% CI 1.64-8.91), African Americans
      (OR 5.96, 95% CI 3.07-11.59), and those with high high-density lipoprotein (OR
      2.82, 95% CI 1.48-5.37) showed greater odds of disagreement. CONCLUSIONS:
      Improved risk assessment methods are needed to identify patients with diabetes
      mellitus who benefit from aspirin for the primary prevention of CVD. Prospective
      trials are needed to provide additional evidence for aspirin use in this
      population.

PMID- 24945173
TI  - Comorbidity of tinea pedis and onychomycosis and evaluation of risk factors in
      Latino immigrant poultry processing and other manual laborers.
AB  - OBJECTIVES: Latino immigrant workers experience elevated rates of skin disease
      that result from their working and living conditions. Working in manual
      occupations exposes workers to a variety of challenges, including occlusive
      shoes, vigorous physical activity, and wet conditions. These challenges
      predispose workers to fungal infection. The objectives of this article are to
      examine the comorbidity of tinea pedis and onychomycosis and to identify possible
      risk factors among Latino immigrant poultry and nonpoultry workers in western
      North Carolina. METHODS: Data were obtained from a cross-sectional study
      conducted between June 2009 and November 2010 in rural western North Carolina
      among 518 manual Latino immigrant workers to assess their occupational injuries.
      Participants completed a face-to-face interview and a dermatologic examination.
      RESULTS: Nearly one-third of the participants (32%) were diagnosed as having
      onychomycosis and more than one-third (37.8%) were diagnosed as having tinea
      pedis. There was a greater prevalence of tinea pedis in men than women (71.3% vs
      28.7%, respectively). Of the 518 participants, 121 (23.5%) had both conditions.
      Participants who reported the use of occlusive shoes as "always" or "most of the
      time" had a higher prevalence of comorbid onychomycosis and tinea pedis than the
      rest of the group. CONCLUSIONS: Comorbidity of tinea pedis and onychomycosis is
      common among immigrant Latino men and women who perform manual labor. Further
      studies confirming the presence and type of dermatophyte should be conducted.

PMID- 24945174
TI  - Electronic health records: an awkward third wheel.

PMID- 24945175
TI  - Commentary on "electronic health records: an awkward third wheel".

PMID- 24945176
TI  - Incidence and predictors of vancomycin-associated nephrotoxicity.
AB  - OBJECTIVES: Earlier studies reported a low incidence of vancomycin-associated
      nephrotoxicity (VAN); however, recent studies have reported higher incidences
      exceeding 30%. Predictors of nephrotoxicity are not well defined. In this study
      we aimed to better estimate the incidence and evaluate predictors of VAN in a
      cohort of patients predominated by long treatment courses. METHODS: We conducted
      a retrospective study on patients treated with vancomycin while in the hospital
      and who were observed closely through the Outpatient Parenteral Antibiotic
      Therapy program. Nephrotoxicity was defined as an increase in the serum
      creatinine level of 0.5 mg/dL or 50% from baseline on at least two consecutive
      readings while taking vancomycin. We compared the patients who developed
      nephrotoxicity with those who did not with regard to vancomycin dosing, trough
      levels, baseline serum creatinine, underlying infection, residence in the
      critical care unit, comorbid conditions, concurrent nephrotoxic treatments, and
      baseline characteristics. RESULTS: Of 579 patients, 154 (26.6%) developed
      nephrotoxicity. Ninety patients developed VAN within the first 14 days of
      treatment, whereas 64 patients developed nephrotoxicity after 14 days of
      treatment. The median time to development of nephrotoxicity was 9 days. Admission
      to the intensive care unit, concurrent use of loop diuretics, and comorbidity
      with cirrhosis were independently associated with nephrotoxicity. A higher
      baseline creatinine value was unexpectedly associated with a lower incidence of
      nephrotoxicity (P = 0.0016). CONCLUSIONS: VAN is not an uncommon outcome in both
      short- and long-term treatment courses. Admission to the intensive care unit
      while receiving treatment, concurrent treatment with a loop diuretic, an
      underlying diagnosis of cirrhosis, and the initial trough level appear to be the
      main risk factors for nephrotoxicity. Unexpectedly, elevated baseline creatinine
      levels appeared to be protective and this could be the result of careful use of
      vancomycin among individuals with relatively higher baseline creatinine values.

PMID- 24945177
TI  - Commentary on "incidence and predictors of vancomycin-associated nephrotoxicity".

PMID- 24945178
TI  - Costs and savings associated with implementation of a police crisis intervention
      team.
AB  - OBJECTIVES: Police crisis intervention teams (CIT) have demonstrated their
      effectiveness in reducing injury to law enforcement personnel and citizens and
      the criminalization of mental illness; however, their financial effect has not
      been fully investigated. The objective of the study was to determine the total
      costs or total savings associated with implementing a CIT program in a medium
      size city. METHODS: The costs and savings associated with the implementation of a
      CIT program were analyzed in a medium-size city, Louisville, Kentucky, 9 years
      after the program's initiation. Costs associated with officer training, increased
      emergency psychiatry visits, and hospital admissions resulting from CIT activity
      were compared with the savings associated with diverted hospitalizations and
      reduced legal bookings. RESULTS: Based on an average of 2400 CIT calls annually,
      the overall costs associated with CIT per year were $2,430,128 ($146,079 for
      officer training, $1,768,536 for hospitalizations of patients brought in by CIT
      officers, $508,690 for emergency psychiatry evaluations, and $6823 for arrests).
      The annual savings of the CIT were $3,455,025 ($1,148,400 in deferred
      hospitalizations, $2,296,800 in reduced inpatient referrals from jail, and $9825
      in avoided bookings and jail time). The balance is $1,024,897 in annual cost
      savings. CONCLUSIONS: The net financial effect of a CIT program is of modest
      benefit; however, much of this analysis was based on estimates and average length
      of stay. Furthermore, the costs and savings associated with officer or citizen
      injuries were not included because there was inadequate information about their
      prevalence and costs. Finally, this analysis does not take into account the
      nonmonetary gains of a CIT program.

PMID- 24945180
TI  - Commentary on "survey of internal medicine physicians trained in three different
      eras: reflections on duty-hour reform".

PMID- 24945179
TI  - Survey of internal medicine physicians trained in three different eras:
      reflections on duty-hour reform.
AB  - OBJECTIVES: To survey internal medicine physicians and residents who have
      completed residency in three different eras of medical training regarding their
      experiences during their intern year and their perceptions of duty-hour reform.
      METHODS: An online survey was administered to 268 residents, fellows, and staff
      physicians who had completed or were completing residency during one of three
      eras of training: before the 80-hour work week, after the 80-hour work week
      (instituted in 2003), and after the 16-hour limit on continuous shifts for
      interns (instituted in 2011). The survey assessed experiences during their intern
      year of residency and perceptions regarding resident duty-hour reform. RESULTS:
      The majority of respondents (n = 32; 54%) indicated that duty-hour restrictions
      would result in residents being less prepared for their future careers. In
      addition, 36% (n = 21) of respondents anticipated a decrease in the quality of
      patient care under the restricted duty hours. A total of 41% (n = 24) were
      undecided regarding the impact of duty-hour reform on patient care. Respondents
      reported time spent on independent study, research, and conference attendance did
      not increase following the institution of duty-hour restrictions. CONCLUSIONS:
      Survey responses indicated that after 18 months of experience with the
      Accreditation Council for Graduate Medical Education duty-hour restrictions,
      physician opinions were mixed and a substantial number remain undecided regarding
      the impact of duty-hour restrictions on resident career preparedness and the
      quality of patient care.

PMID- 24945182
TI  - Intracranial hemorrhage and extensive cerebral venous thrombosis associated with
      ulcerative colitis.

PMID- 24945183
TI  - Can the presence of endoscopic high-risk stigmata be predicted before endoscopy?
      A multivariable analysis using the RUGBE database.
AB  - BACKGROUND: Many aspects in the management of acute upper gastrointestinal
      bleeding rely on pre-esophagogastroduodenoscopy (EGD) stratification of patients
      likely to exhibit high-risk stigmata (HRS); however, data predicting the presence
      of HRS are lacking. OBJECTIVE: To determine clinical and laboratory predictors of
      HRS at the index EGD in patients presenting with acute upper gastrointestinal
      bleeding using retrospective data from a validated national database - the
      Canadian Registry in Upper Gastrointestinal Bleeding and Endoscopy registry.
      methods: Relevant clinical and laboratory parameters were evaluated. HRS was
      defined as spurting, oozing, nonbleeding visible vessel or adherent clot after
      vigorous irrigation. Multivariable modelling was used to identify predictors of
      HRS including age, sex, hematemesis, use of antiplatelet agents, American Society
      of Anesthesiologists (ASA) classification, nasogastric tube aspirate, hemoglobin
      level and elapsed time from the onset of bleeding to EGD. RESULTS: Of the 1677
      patients (mean [+/- SD] age 66.2 +/- 16.8 years; 38.3% female), 28.7% had
      hematemesis, 57.8% had an ASA score of 3 to 5, and the mean hemoglobin level was
      96.8 +/- 27.3 g/L. The mean time from presentation to endoscopy was 22.2 +/- 37.5
      h. The best fitting multivariable model included the following significant
      predictors: ASA score 3 to 5 (OR 2.16 [95% CI 1.71 to 2.74]), a shorter time to
      endoscopy (OR 0.99 [95% CI 0.98 to 0.99]) and a lower initial hemoglobin level
      (OR 0.99 [95% CI 0.99 to 0.99]). CONCLUSION: A higher ASA score, a shorter time
      to endoscopy and lower initial hemoglobin level all significantly predicted the
      presence of endoscopic HRS. These criteria could be used to improve the optimal
      selection of patients requiring more urgent endoscopy.

PMID- 24945184
TI  - Helicobacter pylori infection and markers of gastric cancer risk in Alaska Native
      persons: a retrospective case-control study.
AB  - BACKGROUND: Alaska Native persons experience gastric cancer incidence and
      mortality rates that are three to four times higher than in the general United
      States population. OBJECTIVE: To evaluate pepsinogen I, pepsinogen I/II ratio,
      anti-Helicobacter pylori and cytotoxin-associated gene A (CagA) antibody levels,
      and blood group for their associations with gastric cancer development in Alaska
      Native people. METHODS: The present analysis was a retrospective case-control
      study that matched gastric cancers reported to the Alaska Native Tumor Registry
      from 1969 to 2008 to three controls on known demographic risk factors for H
      pylori infection, using sera from the Alaska Area Specimen Bank. Conditional
      logistic regression evaluated associations between serum markers and gastric
      cancer. RESULTS: A total of 122 gastric cancer cases were included, with sera
      predating cancer diagnosis (mean = 13 years) and 346 matched controls. One
      hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or
      ongoing H pylori infection as measured by anti-H pylori antibody levels. Gastric
      cancer cases had a 2.63-fold increased odds of having positive anti-H pylori
      antibodies compared with their matched controls (P=0.01). In a multivariate
      model, noncardia gastric cancer (n=94) was associated with anti-H pylori
      antibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR
      6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA
      antibodies or pepsinogen I/II ratio was found. CONCLUSION: Alaska Native people
      with gastric cancer had increased odds of previous H pylori infection. Low
      pepsinogen I level may function as a precancer marker for noncardia cancer.

PMID- 24945185
TI  - High prevalence of esophageal dysmotility in asymptomatic obese patients.
AB  - BACKGROUND: Obesity is an important health problem affecting >500 million people
      worldwide. Esophageal dysmotility is a gastrointestinal pathology associated with
      obesity; however, its prevalence and characteristics remain unclear. Esophageal
      dysmotilities have a high prevalence among obese patients regardless of
      gastrointestinal symptoms. OBJECTIVE: To identify the prevalence of esophageal
      dysmotility among obese patients. The secondary goals were to characterize these
      pathologies in obese patients and identify risk factors. METHOD: A prospective
      study from January 2009 to March 2010 at the University of Montreal Hospital
      Centre (Montreal, Quebec) was performed. Every patient scheduled for bariatric
      surgery underwent preoperatory esophageal manometry and was included in the
      study. Manometry was performed according to a standardized protocol with the
      following measures: superior esophageal sphincter - coordination and release
      during deglutition; esophageal body - presence, propagation, length, amplitude
      and type of esophageal waves of contraction; lower esophageal sphincter -
      localization, tone, release, intragastic pressure and intraesophageal pressure.
      All reference values were those used in the digestive motility laboratory. A
      gastrointestinal symptoms questionnaire was completed on the day manometry was
      performed. Chart reviews were performed to identify comorbidities and treatments
      that could influence the results. RESULTS: A total of 53 patients were included
      (mean [+/- SD] age 43 +/- 10 years; mean body mass index 46 +/- 7 kg/m; 70%
      female). Esophageal manometry revealed dysmotility in 51% (n=27) of the patients.
      This dysmotility involved the esophageal body in 74% (n=20) of the patients and
      the inferior sphincter in 11% (n=3). Mixed dysmotility (body and inferior
      sphincter) was found in 15% (n=4) of cases. The esophageal body dysmotilities
      were hypomotility in 85% (n=23) of the patients, either from insignificant waves
      (74% [n=20]), nonpropagated waves (11% [n=3]) or low-amplitude waves (33% [n=9]).
      Gastroesophageal symptoms were found in 66% (n=35) of obese patients, including
      heartburn (66% [n=23]), regurgitation (26% [n=9]), dysphagia (43% [n=15]), chest
      pain (6% [n=2]) and dyspepsia (26% [n=9]). Among symptomatic patients, 51% (n=18)
      had normal manometry and 49% (n=17) had abnormal manometry (statistically
      nonsignificant). Among asymptomatic patients (n=18), 44% (n=8) had normal
      manometry and 56% (n=10) had abnormal manometry (statistically nonsignificant).
      Furthermore, no statistical differences were found between the normal manometry
      group and the abnormal manometry group with regard to medication intake or
      comorbidities. CONCLUSION: Esophageal dysmotilities had a high prevalence in
      obese patients. Gastrointestinal symptoms cannot predict the presence of
      esophageal dysmotility. Hypomotility of the esophageal body is the most common
      dysmotility, especially from the absence of significant waves.

PMID- 24945186
TI  - Screening, detecting and enhancing the yield of previously undiagnosed hepatitis
      B and C in patients with acute medical admissions to hospital: a pilot project
      undertaken at the Vancouver General Hospital.
AB  - BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent an
      increasing health burden and morbidity in Canada. Viral hepatitis, specifically
      HCV, has high prevalence among persons born between 1945 and 1965, with 45% to
      85% of infected adults asymptomatic and unaware of their infection. Screening has
      been shown to be cost effective in the detection and treatment of viral
      hepatitis. OBJECTIVE: To quantify incidence and identify undocumented HBV and HCV
      infection in hospitalized patients at a single centre with secondary analysis of
      risk factors as part of a quality improvement initiative. METHODS: A one-time
      antibody test was conducted in patients admitted to the acute medicine and
      gastroenterology services. RESULTS: Over a 12-week period, hospital screening for
      HBV and HCV was performed in 37.3% of 995 admitted patients. There was
      identification of 15 previously undiagnosed cases of HCV (4%) and 36 undocumented
      cases of occult (ie, antihepatitis B core antigen seropositive) or active (ie,
      hepatitis B surface antigen seropositive) HBV (9.7%). Among patients with
      positive screens, 60% of seropositive HCV patients had no identifiable risk
      factors. CONCLUSIONS: The prevalence of HBV and HCV infection among hospitalized
      patients in Vancouver was higher than that of the general population. Risk
      factors for contraction are often not identified. These results can be used as
      part of an ongoing discussion regarding a 'seek and treat' approach to the
      detection and treatment of chronic blood-borne viral illnesses.

PMID- 24945187
TI  - Physician global assessments or blood tests do not predict mucosal healing in
      ulcerative colitis.
AB  - BACKGROUND: Mucosal healing has been proposed as the therapeutic end point in the
      treatment of patients with ulcerative colitis (UC). OBJECTIVE: To investigate the
      relationship between physician global assessment (PGA) and laboratory blood tests
      (complete blood count, ferritin, C-reactive protein, albumin) and endoscopic
      findings in UC to determine whether they could be adequate surrogates for
      endoscopy. METHODS: A retrospective chart review of patients known to have UC
      from July 2008 to November 2012 was performed at the Health Sciences Centre,
      Winnipeg, Manitoba. Patients included individuals with UC who underwent
      colonoscopy within one month of clinic assessment. Blood tests were standard at
      the time of colonoscopy. Patients presenting through the emergency department,
      those with colonoscopies performed outside the authors' institution, or whose
      colonoscopies and clinical assessments were undertaken more than one month apart
      were excluded. The PGA was used to determine disease activity in patients before
      colonoscopy. The Ulcerative Colitis Endoscopic Index of Severity, a validated
      scoring system to rate endoscopic disease severity in ulcerative colitis, was
      adapted. RESULTS: A total of 154 patients (mean [+/- SD] age 44 +/- 15.7 years)
      with UC were identified including 82 (53%) men. Mean hemoglobin level was 139
      g/L, mean platelet level was 296*10(9)/L, mean ferritin level was 102 MUg/L, mean
      C-reactive protein level was 10 mg/L and mean albumin level was 40 g/L. Using
      endoscopy as the 'gold standard' for assessing UC activity (moderate-severe),
      abnormalities in laboratory parameters and PGA were both highly specific but not
      sensitive for identifying individuals with at least moderately active endoscopic
      disease. The PGA had higher positive and negative predictive values than the
      laboratory parameters. CONCLUSION: Neither blood tests nor PGA could replace
      endoscopy for assessing mucosal healing. When patients experienced active
      symptoms and abnormal serum markers, they were highly likely to have abnormal
      endoscopy. However, inactive symptoms or normal laboratory values did not
      preclude having active endoscopic disease.

PMID- 24945188
TI  - Association between proton pump inhibitor use and spontaneous bacterial
      peritonitis in cirrhotic patients with ascites.
AB  - BACKGROUND: There are data suggesting a link between proton pump inhibitor (PPI)
      use and the development of spontaneous bacterial peritonitis (SBP) in cirrhotic
      patients with ascites; however, these data are controversial. OBJECTIVE: To
      assess whether the use of PPIs in cirrhotic patients with ascites is associated
      with an increased risk for SBP. METHODS: A retrospective case-control study (June
      2004 to June 2010) was conducted at the Centre Hospitalier de l'Universite de
      Montreal in Montreal, Quebec. Fifty-one cirrhotic patients admitted with
      paracentesis-proven SBP (>=250 neutrophils/mm3), occurring within seven days of
      hospital admission, met the inclusion criteria. These patients were matched 1:2
      (for age, Child-Pugh class and year of admission) with 102 comparable cirrhotic
      patients with ascites who were admitted for conditions other than SBP. RESULTS:
      Patients with SBP had a significantly higher rate of pre-hospital PPI use (60.8%)
      compared with cirrhotic patients without SBP (42.2%; P=0.03). On multivariate
      analysis, PPI use was the only factor independently associated with SBP (OR 2.09
      [95% CI 1.04 to 4.23]; P=0.04). Thirty-five (35%) patients in both groups had no
      documented indication for PPI use in their charts. Forty-five percent of the
      remaining cirrhotic patients with SBP had an inappropriate indication, as defined
      in the protocol, for PPI use compared with 25% of controls. CONCLUSIONS:
      Cirrhotic patients with SBP were twice as likely to have taken PPIs than patients
      without SBP. These findings reinforce the association between PPI use and SBP
      observed in other studies. A high percentage of cirrhotic patients were taking a
      PPI without any documented indication.

PMID- 24945189
TI  - Exploring childhood lead exposure through GIS: a review of the recent literature.
AB  - Childhood exposure to lead remains a critical health control problem in the US.
      Integration of Geographic Information Systems (GIS) into childhood lead exposure
      studies significantly enhanced identifying lead hazards in the environment and
      determining at risk children. Research indicates that the toxic threshold for
      lead exposure was updated three times in the last four decades: 60 to 30
      micrograms per deciliter (ug/dL) in 1975, 25 ug/dL in 1985, and 10 ub/dL in 1991.
      These changes revealed the extent of lead poisoning. By 2012 it was evident that
      no safe blood lead threshold for the adverse effects of lead on children had been
      identified and the Center for Disease Control (CDC) currently uses a reference
      value of 5 ug/dL. Review of the recent literature on GIS-based studies suggests
      that numerous environmental risk factors might be critical for lead exposure. New
      GIS-based studies are used in surveillance data management, risk analysis, lead
      exposure visualization, and community intervention strategies where
      geographically-targeted, specific intervention measures are taken. 

PMID- 24945190
TI  - Validation of a framework for measuring hospital disaster resilience using factor
      analysis.
AB  - Hospital disaster resilience can be defined as "the ability of hospitals to
      resist, absorb, and respond to the shock of disasters while maintaining and
      surging essential health services, and then to recover to its original state or
      adapt to a new one." This article aims to provide a framework which can be used
      to comprehensively measure hospital disaster resilience. An evaluation framework
      for assessing hospital resilience was initially proposed through a systematic
      literature review and Modified-Delphi consultation. Eight key domains were
      identified: hospital safety, command, communication and cooperation system,
      disaster plan, resource stockpile, staff capability, disaster training and
      drills, emergency services and surge capability, and recovery and adaptation. The
      data for this study were collected from 41 tertiary hospitals in Shandong
      Province in China, using a specially designed questionnaire. Factor analysis was
      conducted to determine the underpinning structure of the framework. It identified
      a four-factor structure of hospital resilience, namely, emergency medical
      response capability (F1), disaster management mechanisms (F2), hospital
      infrastructural safety (F3), and disaster resources (F4). These factors displayed
      good internal consistency. The overall level of hospital disaster resilience (F)
      was calculated using the scoring model: F = 0.615F1 + 0.202F2 + 0.103F3 +
      0.080F4. This validated framework provides a new way to operationalise the
      concept of hospital resilience, and it is also a foundation for the further
      development of the measurement instrument in future studies. 

PMID- 24945191
TI  - Health risk assessment of ambient air concentrations of benzene, toluene and
      xylene (BTX) in service station environments.
AB  - A comprehensive evaluation of the adverse health effects of human exposures to
      BTX from service station emissions was carried out using BTX exposure data from
      the scientific literature. The data was grouped into different scenarios based on
      activity, location and occupation and plotted as Cumulative Probability
      Distributions (CPD) plots. Health risk was evaluated for each scenario using the
      Hazard Quotient (HQ) at 50% (CEXP50) and 95% (CEXP95) exposure levels. HQ50 and
      HQ95 > 1 were obtained with benzene in the scenario for service station
      attendants and mechanics repairing petrol dispensing pumps indicating a possible
      health risk. The risk was minimized for service stations using vapour recovery
      systems which greatly reduced the benzene exposure levels. HQ50 and HQ95 < 1 were
      obtained for all other scenarios with benzene suggesting minimal risk for most of
      the exposed population. However, HQ50 and HQ95 < 1 was also found with toluene
      and xylene for all scenarios, suggesting minimal health risk. The lifetime excess
      Cancer Risk (CR) and Overall Risk Probability for cancer on exposure to benzene
      was calculated for all Scenarios and this was higher amongst service station
      attendants than any other scenario. 

PMID- 24945192
TI  - The role of civic engagement for men's health and well being in Norway-a
      contribution to public health.
AB  - OBJECTIVES: Using the example of older men volunteering on teams that restore
      historic ships, this article examines the effects of volunteering on the well
      being of older adults. We consider particularly how volunteering impacts levels
      of social engagement and explore how the men's reminiscences as they bond with
      their fellows in highly skilled work helps integrate their life experiences.
      METHODS: Data are based on 14 in-depth interviews with volunteers working on
      historic vessels in Norway. Self-rated health, functional dependency, and well
      being measures were collected using semi-structured questionnaire. RESULTS:
      Volunteering in a context of skilled, group-bonded, culturally prestigious
      activity adds considerably to social capital among elderly men in Norway.
      Respondents explain their involvement in terms of prior relationships and current
      social benefits. They spoke of the value of maintaining past personal connections
      to a particular ship, shipping company, or local community. These were reinforced
      by current social benefits, such as the experience of companionship, unity, and
      the feeling of making an important contribution to the society. The group
      dynamics and strong collective aspect of these voluntary associations maintains
      internal cohesion, and members only leave when forced by increasing age, poor
      health, or insufficient financial resources. CONCLUSIONS: This article
      illuminates a case study of gender-specific engagement of older adults in
      volunteer roles returning high benefits both to participants and society, and
      adds knowledge to public-health programs and policies in the volunteer- and
      cultural-heritage sector.

PMID- 24945193
TI  - Love is hard to understand: the relationship between transitivity and caused
      events in the acquisition of emotion verbs.
AB  - Famously, dog bites man is trivia whereas man bites dog is news. This illustrates
      not just a fact about the world but about language: to know who did what to whom,
      we must correctly identify the mapping between semantic role and syntactic
      position. These mappings are typically predictable, and previous work
      demonstrates that young children are sensitive to these patterns and so could use
      them in acquisition. However, there is only limited and mixed evidence that
      children do use this information to guide acquisition outside of the laboratory.
      We find that children understand emotion verbs which follow the canonical CAUSE
      VERB-PATIENT pattern (Mary frightened/delighted John) earlier than those which do
      not (Mary feared/liked John), despite the latter's higher frequency, suggesting
      children's generalization of the mapping between causativity and transitivity is
      broad and active in acquisition. 

PMID- 24945195
TI  - Iris flocculi.

PMID- 24945194
TI  - A randomized, investigator-masked, double-blind, placebo-controlled trial on
      thalidomide in severe cutaneous sarcoidosis.
AB  - BACKGROUND: Thalidomide use in cutaneous sarcoidosis is based on data from small
      case series or case reports. The objective of this study was to evaluate the
      efficacy and safety of thalidomide in severe cutaneous sarcoidosis. METHODS: This
      study consisted of a randomized, double-bind, parallel, placebo-controlled,
      investigator-masked, multicenter trial lasting 3 months and an open-label study
      from month 3 to month 6. Adults with a clinical and histologic diagnosis of
      cutaneous sarcoidosis were included in nine hospital centers in France. Patients
      were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral
      placebo for 3 months. In the course of an open-label follow-up from month 3 to
      month 6, all patients received thalidomide, 100 mg to 200 mg daily. The
      proportions of patients with a partial or complete cutaneous response at month 3,
      based on at least a 50% improvement in three target lesions scored for area and
      infiltration, were compared across randomization groups. RESULTS: The intent-to
      treat population included 39 patients. None of them had a complete cutaneous
      response. Four out of 20 patients in the thalidomide group (20%) vs four out of
      19 patients in the placebo group (21%) had a partial cutaneous response at month
      3 (difference in proportion of -1% [95% CI, -26% to +24%] for thalidomide vs
      placebo, P = 1.0). Eight patients with side effects were recorded in the
      thalidomide group vs three in the placebo group. We observed a large number of
      adverse event-related discontinuations in patients taking thalidomide in the
      first 3 months (four patients with thalidomide, zero with placebo) and in the 3
      following months (five patients). CONCLUSIONS: At a dose of 100 mg daily for 3
      months, our results do not encourage thalidomide use in cutaneous sarcoidosis.
      TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT0030552; URL: www.clinicaltrials.gov.

PMID- 24945197
TI  - Editorial.

PMID- 24945198
TI  - Private practice : A position statement from the World Psychiatric Association.

PMID- 24945196
TI  - The Parkland Protocol's modified Berne-Norwood criteria predict two tiers of risk
      for traumatic brain injury progression.
AB  - As a basis for venous thromboembolism (VTE) prophylaxis after traumatic brain
      injury (TBI), we have previously published an algorithm known as the Parkland
      Protocol. Patients are classified by risk for spontaneous progression of
      hemorrhage with chemoprophylaxis regimens tailored to each tier. We sought to
      validate this schema. In our algorithm, patients with any of the following are
      classified "low risk" for spontaneous progression: subdural hemorrhage <=8 mm
      thick; epidural hemorrhage <=8 mm thick; contusions <=20 mm in diameter; a single
      contusion per lobe; any amount of subarachnoid hemorrhage; or any amount of
      intraventricular hemorrhage. Patients with any injury exceeding these are
      "moderate risk" for progression, and any patient receiving a monitor or
      craniotomy is "high risk." From February 2010 to November 2012, TBI patients were
      entered into a dedicated database tracking injury types and sizes, risk category
      at presentation, and progression on subsequent computed tomgraphies (CTs). The
      cohort (n=414) was classified as low risk (n=200), moderate risk (n=75), or high
      risk (n=139) after first CT. After repeat CT scan, radiographic progression was
      noted in 27% of low-risk, 53% of moderate-risk, and 58% of high-risk subjects.
      Omnibus analysis of variance test for differences in progression rates was highly
      significant (p<0.0001). Tukey's post-hoc test showed the low-risk progression
      rate to be significantly different than both the moderate- and high-risk arms; no
      difference was noted between the moderate- and high-risk arms themselves. These
      criteria are a valid tool for classifying TBI patients into two categories of
      risk for spontaneous progression. This supports tailored chemoprophylaxis
      regimens for each arm.

PMID- 24945199
TI  - Validation study of PECC (Psychosis Evaluation tool for Common use by
      Caregivers): Interscale validity and inter-rater reliability.
AB  - INTRODUCTION: PECC (Psychosis Evaluation tool for Common use by Caregivers) is a
      recently developed tool for the longitudinal evaluation and follow-up of
      psychotic patients. This integrated evaluation tool covers different functional
      and symptomatic outcome measures, which are relevant for both the patient and the
      planning of interventions. PECC was especially designed to be easily
      implementable in the daily practice of nursing work. In this study we aimed to
      evaluate the inter-rater and interscale validity of PECC. RESULTS: The results
      indicate that both the inter-rater validity and the interscale validity of PECC
      are satisfactory. CONCLUSION: PECC can now be implemented on a large scale. (Int
      J Psych Clin Pract 2002; 6: 135-140).

PMID- 24945200
TI  - Social Adaptation Self-evaluation Scale (SASS): Psychometric analysis as outcome
      measure in the treatment of patients with major depression in the remission
      phase.
AB  - INTRODUCTION: To carry out a psychometric analysis of the Social Adaptation Self
      evaluation Scale (SASS), which has been found very promising during first
      experiences with it in the treatment of depression. METHOD: Patients in the
      remission phase during treatment for a major depressive episode completed the
      SASS over a period of 12 weeks, with monthly assessments. For comparison, the
      Hamilton Depression Scale with the Melancholia Scale (HAM-D/MES) was used as well
      as a self-reporting questionnaire, the Major Depression Inventory (MDI). In the
      psychometric analysis both classical tests (e.g. principal component analysis)
      and modern tests (Mokken analysis with the Loevinger coefficient of homogeneity)
      were applied. RESULTS: The SASS scale with its 21 items was found to contain at
      least three factors, of which the first was a general factor; this however
      explained less than 50% of the variance. A subscale containing the six items with
      the highest factor loadings was found to be a unidimensional scale. This subscale
      showed a much higher responsiveness than the total SASS. However, both SASS
      scales were found to have a lower responsiveness than the Major Depression
      Inventory (MDI) during the first weeks of treatment. CONCLUSION: The SASS was
      found to be a multidimensional scale. However, a six-items subscale (covering
      items with the highest loadings on the first use) was shown to be a
      unidimensional scale and to have a greater responsiveness than the total SASS,
      but still lower than the MDI. (Int J Psych Clin Pract 2002; 6: 141-146).

PMID- 24945202
TI  - Intimation of intent in elderly fatal self-harm: do the elderly who leave suicide
      notes differ from those who do not?
AB  - BACKGROUND: Suicide notes may provide valuable information about suicide victims'
      final thoughts, and thus may be considered as markers of the severity of the
      suicide attempt. However, very few studies have described the characteristics of
      elderly suicide note-writers and their final thoughts. INTRODUCTION: To explore
      whether there is a difference between those who do and do not leave a note among
      the elderly victims of Fatal Self Harm (FSH). Also to examine the content of
      suicide notes and their clinical significance. METHODS: We carried out a
      retrospective review of suicide notes obtained from coroners' records of FSH in
      all over 60 years of age in Cheshire over a period of 13 years (1989-2001). The
      term 'Fatal Self Harm' was applied to all those who were subjects of coroner's
      inquests and attracted verdicts of suicide, misadventure and open verdicts.
      RESULTS: In 71 cases (33%) (43 males, 28 females) (61% M, 39% F) suicide notes
      were reported in the coroner's records. The variables that appeared to differ
      significantly between the note-leavers and non-note-leavers were: a suicide
      verdict, not known to psychiatric services, and method of FSH ( P < 0.05).
      Gender, marital status, history of DSH, social isolation, mental or physical
      morbidity did not appear to differ between the two groups. More of those who took
      an overdose, used plastic bags, electrocuted themselves or used car exhaust fumes
      left suicide notes. Those who died by hanging, jumping from a height, immolation
      or wounding appeared equally likely to leave or not to leave a suicide note.
      Significantly fewer cases who died by drowning left suicide notes ( P < 0.01). No
      statistically significant difference in the content of suicide notes was observed
      in relation to gender or age. CONCLUSION: The failure to identify consistent
      parameters that could differentiate between note-leavers and non-note-leavers
      only leads to the conclusion that a minority of suicide victims leave suicide
      notes. Suicide note-writers may not be typical of the average suicide case and
      information elicited from the study of suicide notes may only apply to note
      writers and not to suicide in general. However, the absence of a suicide note
      must not be considered an indicator of a less serious attempt. (Int J Psych Clin
      in Pract 2002; 6: 155-161).

PMID- 24945201
TI  - Relative humidity and affective disorders.
AB  - INTRODUCTION: Looking at specific weather parameters over a period of time prior
      to hospital admissions may provide evidence of a link between weather conditions
      and some psychiatric conditions such as affective disorders. We examined the
      association between relative humidity (as well as other parameters such as
      sunshine hours, diurnal variations in temperature and rainfall) and psychiatric
      admissions in North Cheshire, UK. METHOD: The daily numbers of all psychiatric
      admissions in North Cheshire in a specified year were analysed in relation to
      meteorological data, which were measured at the meteorological office nearest to
      the study population. RESULTS: We found a significant inverse relationship (with
      time lag) between admissions for affective disorders and relative humidity in the
      week preceding admission. Changes in diurnal variations in temperature, sunshine
      hours and rainfall a few days before admission were also noted, but the findings
      did not achieve statistical significance for any diagnostic category. CONCLUSION:
      The effect of weather parameters on mental health is likely to be influenced by
      other seasonal factors, as well as non-climatic factors, predominantly social,
      that may have contributed to the study findings. Psychiatric admissions reflect
      the behaviour of patients, carers and medical professionals. The complexity of
      this behaviour and the day-of-the-week periodicity may have confounded variations
      associated with the weather. (Int J Psych Clin Pract 2002; 6: 147-153 ).

PMID- 24945203
TI  - Olanzapine oro-dispersible (Velotab TM ) - an alternative to depot?
AB  - INTRODUCTION: Olanzapine oro-dispersible (Velotab TM ) was introduced to the
      United Kingdom in May 2000. It rapidly dissolves in the mouth, and therefore
      patients may find it preferable to swallowing tablets. Another advantage is that
      the opportunity to hide the medication is much reduced. The study examined the
      usage of Velotab TM in a forensic psychiatry setting. METHOD: Drug expenditure
      for different classes of antipsychotic was examined for 6 months before and 7
      months after the introduction of olanzapine Velotab TM . RESULTS: The results
      showed a change in prescribing practice, with a significant inverse correlation
      between the use of Velotab TM and depot medication. CONCLUSION: This suggests
      that forensic psychiatrists, who may have particular concerns about compliance,
      had confidence in oro-dispersible administration as an alternative to depot
      medication. It is suggested that making other neuroleptics available in an oro
      dispersible form would allow for a wider choice of atypicals in populations in
      whom there are significant compliance problems. (Int J Psych Clin Pract 2002; 6:
      163-165).

PMID- 24945204
TI  - A three-year naturalistic follow-up of patients receiving clozapine: Report from
      India.
AB  - INTRODUCTION: Clozapine is a first-line drug for treatment-resistant
      schizophrenia, but studies dealing with long-term outcome are lacking, so we
      decided to carry out such a study. METHODS: Patients with treatment-resistant
      schizophrenia who were recruited in an open-label study three years ago were re
      evaluated using the same parameters: BPRS, PANSS and a side-effect rating
      checklist. RESULTS: Nineteen out of 25 patients who participated in the initial
      study were available for re-evaluation. Two patients had changed to conventional
      neuroleptic medication, and were excluded from the study. A significant reduction
      in psychopathology was observed in 85% of patients. An improvement in social
      functioning was evident, with seven patients pursuing a career independently, and
      another six working with their family members since being started on clozapine.
      All the patients were on clozapine monotherapy, and the average daily dose was
      248.21 mg. No patient required hospitalization and there was no incidence of
      granulocytopenia. CONCLUSIONS: A significant improvement in the psychopathology
      and social functioning of patients was observed with much lower doses of
      clozapine than has been reported elsewhere. The doses used for maintenance were
      lower than those used in the acute phase of treatment. (Int J Psych Clin Pract
      2002; 6: 167-171 ).

PMID- 24945205
TI  - Valproate and quetiapine overdose with benign outcome: A case report.
AB  - We describe a case of intoxication with 16 000 mg of valproate (VPA) and 20 000
      mg of quetiapine (QUE). This is the first case of mixed intoxication with QUE and
      VPA. The ingested dose of QUE is the highest reported in the literature. The
      overdose induced coma and prolonged tachycardia. However, QT did not change
      significantly and blood pressure remained stable. The outcome was benign. Three
      days after the overdose, the patient's medical status improved significantly.
      Despite the overdosage of QUE (25 times the recommended maximum daily dosage and
      100 times the patient's previous daily dosage), only mild tremor and minimal
      akinesia were present, whereas akathisia, rigidity and dystonia were absent. In
      accordance with previous reports on QUE overdosage, this case shows that
      intoxication with high doses of QUE rapidly induces severe deterioration in level
      of consciousness requiring transfer to an intensive care unit. (Int J Psych Clin
      Pract 2002; 6: 173-174 ). 

PMID- 24945206
TI  - Quetiapine in tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is a potentially irreversible side-effect of
      antipsychotic medication. Some atypical antipsychotics, by virtue of their better
      side-effect profile, seem to have an ability to reverse TD. The importance of
      trying to treat TD has become more urgent in view of the medico-legal
      implications of Article 3 of the Human Rights Act, 1998 which states that ''no
      one shall be subjected to inhuman or degrading treatment or punishment'':
      interpretation of this article was successfully used to win a large out-of-court
      settlement for a patient with TD in our region. Though clozapine has been used in
      cases with TD, its role is limited, due to the risk of agranulocytosis. We write
      about three cases with TD who responded well to quetiapine (Seroquel (c) ,
      AstraZeneca), and suggest that more robust research be carried out to investigate
      the initial promise. (Int J Psych Clin Pract 2002; 6: 175-177 ). 

PMID- 24945207
TI  - Lofexidine and desipramine: Interaction results in breakthrough opioid withdrawal
      symptoms.
AB  - A patient was receiving treatment for concurrent opioid and stimulant dependency.
      When desipramine was added to his lofexidine regimen for treatment of stimulant
      withdrawal, there was an exacerbation of opioid withdrawal symptoms. With the
      increasing use of lofexidine for opioid withdrawal, clinicians need to be aware
      of the potential for interactions with tricyclic antidepressants in the treatment
      of concomitant stimulant users. (Int J Psych Clin Pract 2002; 6: 179-181 ). 

PMID- 24945208
TI  - Winning the jackpot and depression: Money cannot buy happiness.
AB  - Life event research examines the effect of life events on the course of
      psychiatric diseases, but the published literature considers almost only negative
      events. We describe the cases of two female patients who had to be hospitalized
      for depression after lottery winnings of over 1M DM. The 4-year follow-up shows a
      good outcome in both patients. Case analyses suggest that in both patients,
      winning was a life event relevant to the development of the depressive episode.
      Desirable life events might influence the course of a psychiatric illness just as
      negative events do. (Int J Psych Clin Pract 2002; 6: 183-186). 

PMID- 24945209
TI  - Erratum.

PMID- 24945211
TI  - The heart of an endurance athlete.

PMID- 24945212
TI  - Eternal sunshine of the rodent mind.

PMID- 24945214
TI  - Laser therapy to regenerate teeth.

PMID- 24945215
TI  - Wheel running not just for lab mice.

PMID- 24945217
TI  - Experimental Biology 2014. 26-30 April 2014, San Diego Convention Center, San
      Diego, CA.

PMID- 24945218
TI  - Newts with superpowers.

PMID- 24945219
TI  - Policy pressure from the Institutional Official.

PMID- 24945220
TI  - Stand by the policy.

PMID- 24945221
TI  - Stick to their guns.

PMID- 24945222
TI  - A role dilemma.

PMID- 24945223
TI  - The search for animal models.

PMID- 24945224
TI  - An improved method for lifting and transporting anesthetized pigs within an
      animal facility.
AB  - Transporting anesthetized pigs in a laboratory setting often requires strenuous
      manual lifting, posing a hazard to the safety of animal care personnel and to the
      welfare of the pigs. The authors developed an improved approach to lifting and
      transporting anesthetized pigs weighing up to 350 kg using mechanical lifts.
      Different equipment was used to accommodate pigs of different sizes as well as
      the building designs of three animal facilities. Using the lifts, anesthetized
      pigs are carried on sheets to maintain their comfort while being transported. The
      approach refines previous methods for handling and transporting anesthetized pigs
      and reduces the risk of injury to personnel. 

PMID- 24945225
TI  - Hyperglycemia and hepatic tumors in ICR mice neonatally injected with
      streptozotocin.
AB  - Repeated, low-dose administration of streptozotocin (STZ) is widely used to
      induce insulin-dependent diabetes mellitus in mice. The authors adapted this
      method using neonatal mice and determined the long-term effects of STZ injection
      in the mice. After receiving intraperitoneal injections of STZ at postnatal day 3
      (P3), P4 and P8, male and female mice were hyperglycemic by week 4. A clear sex
      difference was found, with blood glucose levels in STZ-treated males remaining
      higher than those in STZ-treated females until week 23. Whereas STZ-treated males
      remained hyperglycemic until week 23, STZ-treated females did not have
      significantly higher glucose levels than control mice after week 18.
      Additionally, STZ-treated mice had neoplastic lesions in their livers by week 4,
      with a progression in the severity of these lesions until week 24. The results
      confirm that, in addition to pancreatic beta cell toxicity, STZ has an oncogenic
      effect on the liver when administered to neonates. 

PMID- 24945226
TI  - Facilitate, don't dictate.

PMID- 24945227
TI  - If we win a key battle...

PMID- 24945228
TI  - Medicare meltdown: another lost opportunity.
AB  - Congress once again let physicians down by failing to fix the flawed Medicare
      Sustainable Growth Rate formula and defaulting to a temporary patch for the 17th
      time. Because Congress came closer than ever to solving the problem with
      bipartisan legislation, medicine is eager to get back to the negotiating table
      and capitalize on the progress made this session. 

PMID- 24945229
TI  - Out in the open.

PMID- 24945230
TI  - Playing It SAFER.

PMID- 24945231
TI  - A lost art.

PMID- 24945232
TI  - Medicare data go public.

PMID- 24945233
TI  - Hard evidence.

PMID- 24945234
TI  - Costs of the residency match for fourth-year medical students.
AB  - A vital step in the career of a physician is applying and interviewing for a
      position in a residency program. Unfortunately, the costs associated with this
      process are often not anticipated by fourth-year medical students. The authors
      collected data on these costs from fourth-year medical students in Texas (N=274)
      during 2012-2013. Results suggested that the average cost of this process was
      significant (M=$4783). The costs varied greatly, depending on the medical
      specialty for which the fourth-year medical student applied, with a range
      exceeding $12,000. Most students (60%) paid for these costs with personal
      savings. The authors suggest that documentation of the average cost of applying
      and interviewing for residency would allow future fourth-year medical students to
      make more accurate financial plans, provide evidence for increased financial need
      during the final year of medical school, and initiate an evaluation of the
      current residency match process for cost-saving strategies to decrease the
      financial burden on students. 

PMID- 24945235
TI  - Prediction of digestible energy and gross energy digestibility of feeds and diets
      in ostriches.
AB  - 1. The aim of this study was to assess regression equations able to predict the
      digestible energy (DE) and gross energy digestibility (GEd) of feed ingredients
      and diets for ostriches. 2. Results of chemical-nutritional characteristics from
      17 ingredients (two varieties of maize, two barleys, oat, triticale, wheat bran,
      soybean meal, sunflower meal, beet pulp, maize silage, alfalfa hay, 4 alfalfa
      meals and lupin) and 12 experimental diets were used in a stepwise procedure. 3.
      Acid detergent lignin (ADL) was the first independent variable included in the
      model to predict the DE of all the samples (R(2) = 0.65 and Residual Standard
      Deviation (RSD) 1.02). When the concentration of ash, acid detergent fibre (ADF)
      and crude fibre were included in the model, the R(2) value of the regression
      equation increased (from 0.65 to 0.85) and RSD decreased (from 1.02 to 0.48). 4.
      The ADL concentration was also the first independent variable chosen by the
      stepwise regression analysis for the estimation of GEd from chemical-nutritional
      characteristics of feeds, explaining 57% of the total GEd variation. The
      concentrations of crude protein and ADF included at the second and third steps in
      the model increased the R(2) (up to 0.70 and 0.73, respectively) and decreased
      the RSD values (from 0.29 to 0.21 and 0.20, respectively). When other variables
      as crude fibre, ash and gross energy were included in the model, the coefficient
      of determination and the RSD strongly improved (0.85 and 0.12, respectively).

PMID- 24945236
TI  - Respiratory pharmacotherapy use in patients newly diagnosed with chronic
      obstructive pulmonary disease in a primary care setting in the UK: a
      retrospective cohort study.
AB  - This retrospective cohort study aimed to analyze the prescribing practices of
      general practitioners treating patients with newly diagnosed chronic obstructive
      pulmonary disease (COPD), and to assess characteristics associated with initial
      pharmacotherapy. Patients were identified in the General Practice Research
      Database, a population-based UK electronic medical record (EMR) with data from
      January 1, 2008 to December 31, 2009. Patient characteristics, prescribed COPD
      pharmacotherapies (<=12 months before diagnosis and within 3 months following
      diagnosis), co-morbidities, hospitalizations, and events indicative of a possible
      COPD exacerbation (<=12 months before diagnosis) were analyzed in 7881 patients
      with newly diagnosed COPD. Most patients (64.4%) were prescribed COPD
      pharmacotherapy in the 12 months before diagnosis. Following diagnosis, COPD
      pharmacotherapy was prescribed within 3 months in 85.0% of patients. Short-acting
      bronchodilators alone (22.9%) or inhaled corticosteroids + long-acting beta-2
      agonists (ICS+LABA, 22.1%) were prescribed most frequently. Compared with other
      pharmacotherapies, the prevalence of severe airflow limitation was highest in
      patients prescribed ICS+LABA+long-acting muscarinic antagonists (LAMA). Moderate
      to-severe dyspnea was identified most frequently in patients prescribed a LAMA
      containing regimen. Patients prescribed an ICS-containing regimen had a higher
      prevalence of asthma or possible exacerbations recorded in the EMR than those not
      prescribed ICS. In conclusion, pharmacotherapy prescribed at initial COPD
      diagnosis varied by disease severity indicators as assessed by airflow
      limitation, dyspnea, history of asthma, and possible exacerbations. Frequent
      prescription of COPD pharmacotherapies before the first-recorded COPD diagnosis
      indicates a delay between obstructive lung disease presentation in primary care
      practice and assignment of a medical diagnosis.

PMID- 24945238
TI  - Prevalence estimates of gestational diabetes mellitus in the United States,
      Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010.
AB  - INTRODUCTION: The true prevalence of gestational diabetes mellitus (GDM) is
      unknown. The objective of this study was 1) to provide the most current GDM
      prevalence reported on the birth certificate and the Pregnancy Risk Assessment
      Monitoring System (PRAMS) questionnaire and 2) to compare GDM prevalence from
      PRAMS across 2007-2008 and 2009-2010. METHODS: We examined 2010 GDM prevalence
      reported on birth certificate or PRAMS questionnaire and concordance between the
      sources. We included 16 states that adopted the 2003 revised birth certificate.
      We also examined trends from 2007 through 2010 and included 21 states that
      participated in PRAMS for all 4 years. We combined GDM prevalence across 2-year
      intervals and conducted t tests to examine differences. Data were weighted to
      represent all women delivering live births in each state. RESULTS: GDM prevalence
      in 2010 was 4.6% as reported on the birth certificate, 8.7% as reported on the
      PRAMS questionnaire, and 9.2% as reported on either the birth certificate or
      questionnaire. The agreement between sources was 94.1% (percent positive
      agreement = 3.7%, percent negative agreement = 90.4%). There was no significant
      difference in GDM prevalence between 2007-2008 (8.1%) and 2009-2010 (8.5%, P =
      .15). CONCLUSION: Our results indicate that GDM prevalence is as high as 9.2% and
      is more likely to be reported on the PRAMS questionnaire than the birth
      certificate. We found no statistical difference in GDM prevalence between the 2
      phases. Further studies are needed to understand discrepancies in reporting GDM
      by data source.

PMID- 24945239
TI  - Chronic condition self-management surveillance: what is and what should be
      measured?
AB  - INTRODUCTION: The rapid growth in chronic disease prevalence, in particular the
      prevalence of multiple chronic conditions, poses a significant and increasing
      burden on the health of Americans. Maximizing the use of proven self-management
      (SM) strategies is a core goal of the US Department of Health and Human Services.
      Yet, there is no systematic way to assess how much SM or self-management support
      (SMS) is occurring in the United States. The purpose of this project was to
      identify appropriate concepts or measures to incorporate into national SM and SMS
      surveillance. METHODS: A multistep process was used to identify candidate
      concepts, assess existing measures, and select high-priority concepts for further
      development. A stakeholder survey, an environmental scan, subject matter expert
      feedback, and a stakeholder priority-setting exercise were all used to select the
      high-priority concepts for development. RESULTS: The stakeholder survey gathered
      feedback on 32 candidate concepts; 9 concepts were endorsed by more than 66% of
      respondents. The environmental scan indicated few existing measures that
      adequately reflected the candidate concepts, and those that were identified were
      generally specific to a defined condition and not gathered on a population basis.
      On the basis of the priority setting exercises and environmental scan, we
      selected 1 concept from each of 5 levels of behavioral influence for immediate
      development as an SM or SMS indicator. CONCLUSION: The absence of any available
      measures to assess SM or SMS across the population highlights the need to develop
      chronic condition SM surveillance that uses national surveys and other data
      sources to measure national progress in SM and SMS.

PMID- 24945237
TI  - Community-based settings and sampling strategies: implications for reducing
      racial health disparities among black men, New York City, 2010-2013.
AB  - INTRODUCTION: Rates of screening colonoscopies, an effective method of preventing
      colorectal cancer, have increased in New York City over the past decade, and
      racial disparities in screening have declined. However, vulnerable subsets of the
      population may not be reached by traditional surveillance and intervention
      efforts to improve colorectal cancer screening rates. METHODS: We compared rates
      of screening colonoscopies among black men aged 50 or older from a citywide
      random-digit-dial sample and a location-based sample focused on hard-to-reach
      populations to evaluate the representativeness of the random-digit-dial sample.
      The location-based sample (N = 5,568) was recruited from 2010 through 2013 from
      community-based organizations in New York City. Descriptive statistics were used
      to compare these data with data for all black men aged 50 or older from the 2011
      cohort of the Community Health Survey (weighted, N = 334) and to compare rates by
      community-based setting. RESULTS: Significant differences in screening
      colonoscopy history were observed between the location-based and random-digit
      dial samples (49.1% vs 62.8%, P < .001). We observed significant differences
      between participants with and without a working telephone among the location
      based sample and between community-based settings. CONCLUSIONS: Vulnerable
      subsets of the population such as those with inconsistent telephone access are
      excluded from random-digit-dial samples. Practitioners and researchers should
      consider the target population of proposed interventions to address disparities,
      and whether the type of setting reaches those most in need of services.

PMID- 24945240
TI  - Flavored tobacco use among Canadian students in grades 9 through 12: prevalence
      and patterns from the 2010-2011 youth smoking survey.
AB  - INTRODUCTION: This study examined patterns of use of flavored tobacco products in
      a nationally generalizable sample of Canadian students in grades 9 through 12
      after the implementation of a national ban on certain flavored tobacco products.
      METHODS: Data from the 2010-2011 Youth Smoking Survey, a nationally generalizable
      sample of Canadian students in grades 9 through 12 (n = 31,396), were used to
      examine tobacco product use. Logistic regression models were used to examine
      differences in use of flavored tobacco products (cigarettes, pipes, little cigars
      or cigarillos, cigars, roll-your-own cigarettes, bidis, smokeless tobacco, water
      pipes, and blunt wraps) by sociodemographic and regional characteristics.
      RESULTS: Approximately 52% of young tobacco users used flavored products in the
      previous 30 days. Flavored tobacco use varied by product type and ranged from 32%
      of cigarette smokers reporting menthol smoking to 70% of smokeless tobacco users
      reporting using flavored product in the previous 30 days. The percentage of last
      30-day users who used flavored tobacco was significantly higher in Quebec than in
      Ontario and significantly higher among youths who received weekly spending money
      than among those who received no money. CONCLUSION: More than half of tobacco
      users in grades 9 through 12 in Canada use flavored tobacco, despite a national
      ban on certain flavored tobacco products.

PMID- 24945241
TI  - Physiotherapy and physical functioning post-stroke: exercise habits and
      functioning 4 years later? Long-term follow-up after a 1-year long-term
      intervention period: a randomized controlled trial.
AB  - INTRODUCTION: Physical activity is mandatory if patients are to remain healthy
      and independent after stroke. OBJECTIVE: Maintenance of motor function, tone,
      grip strength, balance, mobility, gait, independence in personal and instrumental
      activities of daily living, health-related quality-of-life and an active
      lifestyle 4 years post-stroke. METHODS: A prospective randomized controlled
      trial. RESULTS: Four years post-stroke, 37 of the 75 participating persons were
      eligible for follow-up; 19 (54.3%) from the intensive exercise group and 18 (45%)
      from the regular exercise group. Both groups were performing equally well with no
      significant differences in total scores on the BI (p = 0.3), MAS (p = 0.4), BBS
      (p = 0.1), TUG (p = 0.08), 6MWT (p = 0.1), bilateral grip strength (affected
      hand, p = 0.8; non-affected hand, p = 0.9) nor in the items of NHP (p > 0.005).
      Independence in performing the IADL was 40%, while 60% had help from relatives or
      community-based services. CONCLUSION: This longitudinal study shows that persons
      with stroke in two groups with different exercise regimes during the first year
      after stroke did not differ in long-term outcomes. Both groups maintained
      function and had a relatively active life style 4 years after the acute incident.
      The results underline the importance of follow-up testing and encouragement to
      exercise, to motivate and sustain physical activity patterns, to maintain
      physical function, not only in the acute but also in the chronic phase of stroke.

PMID- 24945243
TI  - The Women's Health Care Empowerment Model as a Catalyst for Change in Developing
      Countries.
AB  - Women's empowerment has been attempted through a number of different fields
      including the realms of politics, finance, and education, yet none of these
      domains are as promising as health care. Here we review preliminary work in this
      domain and introduce a model for women's empowerment through involvement in
      health care, titled the "women's health care empowerment model." Principles upon
      which our model is built include: acknowledging the appropriate definition of
      empowerment within the cultural context, creating a women's network for
      communication, integrating local culture and tradition into training women, and
      increasing the capability of women to care for their children and other women. 

PMID- 24945242
TI  - Computer-Aided Mandibular Reconstruction With Vascularized Iliac Crest Bone Flap
      and Simultaneous Implant Surgery.
AB  - The intention of oral rehabilitation in patients with mandibular defects is an
      early prosthetic treatment with maximum possible functionality and high accuracy.
      The present study describes a new computer-aided technique for mandibular
      reconstruction using a free vascularized iliac flap and simultaneous insertion of
      dental implants into the flap while it is still pedicled at the donor site. Based
      on preoperative computerized tomography data of the facial skeleton and the iliac
      crest donor site, a surgical guide transferred the virtual plan including
      information on the transplant dimensions and shape as well as the position of the
      dental implants into real-time surgery. Using postoperative computerized
      tomography scans, the actual situation were compared with the preoperative
      simulation. A mean difference of 0.75 mm (SD +/- 0.72) for the flap shape and
      0.70 mm (SD +/- 0.44) for the implant position analysis was determined. A
      calculation of the closest point distance showed a surface deviation of <2 mm for
      the shape analysis in 93.3% of the values and <1 mm for implant position in 75.2%
      of the values. The mean angular deviation was 3.65 degrees . Virtual surgical
      planning is a suitable method for mandibular reconstruction with vascularized
      iliac crest flaps and simultaneous implant surgery. It can be used to restore the
      anatomy of the mandible with a high accuracy and can help to shorten subsequent
      dental rehabilitation.

PMID- 24945246
TI  - A digital framework to build, visualize and analyze a gene expression atlas with
      cellular resolution in zebrafish early embryogenesis.
AB  - A gene expression atlas is an essential resource to quantify and understand the
      multiscale processes of embryogenesis in time and space. The automated
      reconstruction of a prototypic 4D atlas for vertebrate early embryos, using
      multicolor fluorescence in situ hybridization with nuclear counterstain, requires
      dedicated computational strategies. To this goal, we designed an original
      methodological framework implemented in a software tool called Match-IT. With
      only minimal human supervision, our system is able to gather gene expression
      patterns observed in different analyzed embryos with phenotypic variability and
      map them onto a series of common 3D templates over time, creating a 4D atlas.
      This framework was used to construct an atlas composed of 6 gene expression
      templates from a cohort of zebrafish early embryos spanning 6 developmental
      stages from 4 to 6.3 hpf (hours post fertilization). They included 53 specimens,
      181,415 detected cell nuclei and the segmentation of 98 gene expression patterns
      observed in 3D for 9 different genes. In addition, an interactive visualization
      software, Atlas-IT, was developed to inspect, supervise and analyze the atlas.
      Match-IT and Atlas-IT, including user manuals, representative datasets and video
      tutorials, are publicly and freely available online. We also propose
      computational methods and tools for the quantitative assessment of the gene
      expression templates at the cellular scale, with the identification,
      visualization and analysis of coexpression patterns, synexpression groups and
      their dynamics through developmental stages. 

PMID- 24945245
TI  - Facile bench-top fabrication of enclosed circular microchannels provides 3D
      confined structure for growth of prostate epithelial cells.
AB  - We present a simple bench-top method to fabricate enclosed circular channels for
      biological experiments. Fabricating the channels takes less than 2 hours by using
      glass capillaries of various diameters (from 100 um up to 400 um) as a mould in
      PDMS. The inner surface of microchannels prepared in this way was coated with a
      thin membrane of either Matrigel or a layer-by-layer polyelectrolyte to control
      cellular adhesion. The microchannels were then used as scaffolds for 3D-confined
      epithelial cell culture. To show that our device can be used with several
      epithelial cell types from exocrine glandular tissues, we performed our
      biological studies on adherent epithelial prostate cells (non-malignant RWPE-1
      and invasive PC3) and also on breast (non-malignant MCF10A) cells We observed
      that in static conditions cells adhere and proliferate to form a confluent layer
      in channels of 150 um in diameter and larger, whereas cellular viability
      decreases with decreasing diameter of the channel. Matrigel and PSS (poly (sodium
      4-styrenesulphonate)) promote cell adhesion, whereas the cell proliferation rate
      was reduced on the PAH (poly (allylamine hydrochloride))-terminated surface.
      Moreover infusing channels with a continuous flow did not induce any cellular
      detachment. Our system is designed to simply grow cells in a microchannel
      structure and could be easily fabricated in any biological laboratory. It offers
      opportunities to grow epithelial cells that support the formation of a light.
      This system could be eventually used, for example, to collect cellular
      secretions, or study cell responses to graduated hypoxia conditions, to chemicals
      (drugs, siRNA, ...) and/or physiological shear stress. 

PMID- 24945244
TI  - Protective efficacy of passive immunization with monoclonal antibodies in animal
      models of H5N1 highly pathogenic avian influenza virus infection.
AB  - Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause
      severe pneumonia and multiple organ failure in humans, with reported case
      fatality rates of more than 60%. To develop a clinical antibody therapy, we
      generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed
      strong neutralizing activity against H5N1 HPAI viruses isolated from humans and
      evaluated its protective potential in mouse and nonhuman primate models of H5N1
      HPAI virus infections. Passive immunization with MAb ch61 one day before or after
      challenge with a lethal dose of the virus completely protected mice, and partial
      protection was achieved when mice were treated 3 days after the challenge. In a
      cynomolgus macaque model, reduced viral loads and partial protection against
      lethal infection were observed in macaques treated with MAb ch61 intravenously
      one and three days after challenge. Protective effects were also noted in
      macaques under immunosuppression. Though mutant viruses escaping from
      neutralization by MAb ch61 were recovered from macaques treated with this MAb
      alone, combined treatment with MAb ch61 and peramivir reduced the emergence of
      escape mutants. Our results indicate that antibody therapy might be beneficial in
      reducing viral loads and delaying disease progression during H5N1 HPAI virus
      infection in clinical cases and combined treatment with other antiviral compounds
      should improve the protective effects of antibody therapy against H5N1 HPAI virus
      infection. 

PMID- 24945247
TI  - Crossing the interspecies barrier: opening the door to zoonotic pathogens.

PMID- 24945248
TI  - Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by
      fusion to MHC class ii invariant chain.
AB  - The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to
      CD4+ T cells, but enhanced CD8+ T cells responses have been reported after
      vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen
      of interest. In this study we assessed whether fusion of the malarial antigen, ME
      TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following
      single or heterologous prime-boost vaccination of mice with a recombinant
      chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus
      Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were
      observed, with the largest increases observed following a ChAd63-MVA heterologous
      prime-boost regimen. Studies in non-human primates confirmed the ability of Ii
      fusion to augment the T cell response, where a 4-fold increase was maintained up
      to 11 weeks after the MVA boost. Of the numerous different approaches explored to
      increase vectored vaccine induced immunogenicity over the years, fusion to the
      invariant chain showed a consistent enhancement in CD8+ T cell responses across
      different animal species and may therefore find application in the development of
      vaccines against human malaria and other diseases where high levels of cell
      mediated immunity are required. 

PMID- 24945249
TI  - Diverse interleukin-7 mRNA transcripts in Chinese tree shrew (Tupaia belangeri
      chinensis).
AB  - Interleukin-7 (IL7) is a pleiotropic cytokine that is actively involved in the
      immune system. The Chinese tree shrew (Tupaia belangeri chinensis) has been
      proposed as an alternative experimental animal to primates in biomedical
      research. However, there is a lack of biological knowledge about the immune
      system of the tree shrew. In this study, we cloned the IL7 gene (tIL7) in the
      Chinese tree shrew and quantified the expression of mRNA transcripts in eight
      tissues (heart, liver, spleen, lung, kidney, intestine, skeletal muscle and
      brain) from 20 individuals. Eleven tIL7 mRNA transcripts were identified in
      different tissues. The canonical form (tIL7c) had a length of 1817 bp and encoded
      a predicted gene product with 177 amino acids. Phylogenetic analyses based on the
      amino acid sequences revealed a considerably large genetic difference between
      tree shrew and human. Quantification of mRNA expression of transcripts tIL7c,
      tIL7-sv1, tIL7-sv2 and tIL7-sv3 showed that these transcripts were expressed in
      all tissues, albeit the expression levels varied in different tissues.
      Transcripts tIL7c, tIL7-sv1, and tIL7-sv2 had the lowest expression in brain, and
      tIL7-sv3 had a dramatically high mRNA expression in skeletal muscle and heart.
      The mRNA expression levels of tIL7c and tIL7-sv1 were significantly increased
      upon ploy(I:C) stimulation in tree shrew primary renal cells. As with human full
      length IL7, tIL7c, tIL7-sv1, tIL7-sv2 and tIL7-sv3 showed similar a subcellular
      localization pattern. Our results identified diverse tIL7 transcripts in the
      Chinese tree shrew, which may play a potential role in modulating IL7-regulated
      biological effects. 

PMID- 24945250
TI  - Mechanisms of pyrethroid resistance in the dengue mosquito vector, Aedes aegypti:
      target site insensitivity, penetration, and metabolism.
AB  - Aedes aegypti is the major vector of yellow and dengue fevers. After 10
      generations of adult selection, an A. aegypti strain (SP) developed 1650-fold
      resistance to permethrin, which is one of the most widely used pyrethroid
      insecticides for mosquito control. SP larvae also developed 8790-fold resistance
      following selection of the adults. Prior to the selections, the frequencies of
      V1016G and F1534C mutations in domains II and III, respectively, of voltage
      sensitive sodium channel (Vssc, the target site of pyrethroid insecticide) were
      0.44 and 0.56, respectively. In contrast, only G1016 alleles were present after
      two permethrin selections, indicating that G1016 can more contribute to the
      insensitivity of Vssc than C1534. In vivo metabolism studies showed that the SP
      strain excreted permethrin metabolites more rapidly than a susceptible SMK
      strain. Pretreatment with piperonyl butoxide caused strong inhibition of
      excretion of permethrin metabolites, suggesting that cytochrome P450
      monooxygenases (P450s) play an important role in resistance development. In vitro
      metabolism studies also indicated an association of P450s with resistance.
      Microarray analysis showed that multiple P450 genes were over expressed during
      the larval and adult stages in the SP strain. Following quantitative real time
      PCR, we focused on two P450 isoforms, CYP9M6 and CYP6BB2. Transcription levels of
      these P450s were well correlated with the rate of permethrin excretion and they
      were certainly capable of detoxifying permethrin to 4'-HO-permethrin. Over
      expression of CYP9M6 was partially due to gene amplification. There was no
      significant difference in the rate of permethrin reduction from cuticle between
      SP and SMK strains. 

PMID- 24945251
TI  - Effect of media use on HIV-related stigma in Sub-Saharan Africa: a cross
      sectional study.
AB  - It is known that HIV-related stigma hinders prevention efforts. Previous studies
      have documented that HIV-related stigma may be associated with socioeconomic and
      socioecological factors. Mass media use may moderate this association, but there
      is limited research addressing that possibility. In this study, based on cross
      sectional data pooled from the 2006-2011 Demographic and Health Surveys of 11 sub
      Saharan African countries (N = 204,343), we investigated the moderating effects
      of exposure to mass media on HIV-related stigma. Hierarchical regression analysis
      indicated that HIV-related stigma tends to be higher among rural residents and
      individuals with low levels of education and HIV knowledge, as well as those who
      do not know people living with HIV. Media use was generally associated with low
      levels of HIV-related stigma, and attenuated the gap between individuals with
      high and low educational levels. However, the effect of mass media was found to
      be stronger among urbanites rather than among rural residents, which could lead
      to a widening gap between the two groups in endorsement of HIV-related stigma.
      The implication of this study regarding the effect of media use on HIV-related
      stigma in sub-Saharan Africa is twofold: 1) mass media may have the potential to
      minimize the gap in HIV-related stigma between individuals with high and low
      educational levels, and hence future efforts of reducing HIV-related stigma in
      the region may benefit from utilizing media; 2) due perhaps to low media
      penetration to rural sub-Saharan Africa, mass media could have the unintended
      effect of widening the urban-rural gap further unless other more customized and
      rural-focused communication interventions are put in place. 

PMID- 24945252
TI  - The epidermal growth factor receptor critically regulates endometrial function
      during early pregnancy.
AB  - Infertility and adverse gynecological outcomes such as preeclampsia and
      miscarriage represent significant female reproductive health concerns. The
      spatiotemporal expression of growth factors indicates that they play an important
      role in pregnancy. The goal of this study is to define the role of the ERBB
      family of growth factor receptors in endometrial function. Using conditional
      ablation in mice and siRNA in primary human endometrial stromal cells, we
      identified the epidermal growth factor receptor (Egfr) to be critical for
      endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led
      to only a modest reduction in litter size, mice lacking Egfr expression are
      severely subfertile. Pregnancy demise occurred shortly after blastocyst
      implantation due to defects in decidualization including decreased proliferation,
      cell survival, differentiation and target gene expression. To place Egfr in a
      genetic regulatory hierarchy, transcriptome analyses was used to compare the gene
      signatures from mice with conditional ablation of Egfr, wingless-related MMTV
      integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing
      that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also
      regulate distinct physiological functions. In primary human endometrial stromal
      cells, marker gene expression, a novel high content image-based approach and
      phosphokinase array analysis were used to demonstrate that EGFR is a critical
      regulator of human decidualization. Furthermore, inhibition of EGFR signaling
      intermediaries WNK1 and AKT1S1, members identified in the kinase array and
      previously unreported to play a role in the endometrium, also attenuate
      decidualization. These results demonstrate that EGFR plays an integral role in
      establishing the cellular context necessary for successful pregnancy via the
      activation of intricate signaling and transcriptional networks, thereby providing
      valuable insight into potential therapeutic targets. 

PMID- 24945253
TI  - A prognostic model of triple-negative breast cancer based on miR-27b-3p and node
      status.
AB  - OBJECTIVE: Triple-negative breast cancer (TNBC) is an aggressive but
      heterogeneous subtype of breast cancer. This study aimed to identify and validate
      a prognostic signature for TNBC patients to improve prognostic capability and to
      guide individualized treatment. METHODS: We retrospectively analyzed the
      prognostic performance of clinicopathological characteristics and miRNAs in a
      training set of 58 patients with invasive ductal TNBC diagnosed between 2002 and
      2012. A prediction model was developed based on independent clinicopathological
      and miRNA covariates. The prognostic value of the model was further validated in
      a separate set of 41 TNBC patients diagnosed between 2007 and 2008. RESULTS: Only
      lymph node status was marginally significantly associated with poor prognosis of
      TNBC (P = 0.054), whereas other clinicopathological factors, including age, tumor
      size, histological grade, lymphovascular invasion, P53 status, Ki-67 index, and
      type of surgery, were not. The expression levels of miR-27b-3p, miR-107, and miR
      103a-3p were significantly elevated in the metastatic group compared with the
      disease-free group (P value: 0.008, 0.005, and 0.050, respectively). The Cox
      proportional hazards regression analysis revealed that lymph node status and miR
      27b-3p were independent predictors of poor prognosis (P value: 0.012 and 0.027,
      respectively). A logistic regression model was developed based on these two
      independent covariates, and the prognostic value of the model was subsequently
      confirmed in a separate validation set. The two different risk groups, which were
      stratified according to the model, showed significant differences in the rates of
      distant metastasis and breast cancer-related death not only in the training set
      (P value: 0.001 and 0.040, respectively) but also in the validation set (P value:
      0.013 and 0.012, respectively). CONCLUSION: This model based on miRNA and node
      status covariates may be used to stratify TNBC patients into different prognostic
      subgroups for potentially individualized therapy.

PMID- 24945258
TI  - Unification theory of optimal life histories and linear demographic models in
      internal stochasticity.
AB  - Life history of organisms is exposed to uncertainty generated by internal and
      external stochasticities. Internal stochasticity is generated by the randomness
      in each individual life history, such as randomness in food intake, genetic
      character and size growth rate, whereas external stochasticity is due to the
      environment. For instance, it is known that the external stochasticity tends to
      affect population growth rate negatively. It has been shown in a recent
      theoretical study using path-integral formulation in structured linear
      demographic models that internal stochasticity can affect population growth rate
      positively or negatively. However, internal stochasticity has not been the main
      subject of researches. Taking account of effect of internal stochasticity on the
      population growth rate, the fittest organism has the optimal control of life
      history affected by the stochasticity in the habitat. The study of this control
      is known as the optimal life schedule problems. In order to analyze the optimal
      control under internal stochasticity, we need to make use of "Stochastic Control
      Theory" in the optimal life schedule problem. There is, however, no such kind of
      theory unifying optimal life history and internal stochasticity. This study
      focuses on an extension of optimal life schedule problems to unify control theory
      of internal stochasticity into linear demographic models. First, we show the
      relationship between the general age-states linear demographic models and the
      stochastic control theory via several mathematical formulations, such as path
      integral, integral equation, and transition matrix. Secondly, we apply our theory
      to a two-resource utilization model for two different breeding systems:
      semelparity and iteroparity. Finally, we show that the diversity of resources is
      important for species in a case. Our study shows that this unification theory can
      address risk hedges of life history in general age-states linear demographic
      models. 

PMID- 24945255
TI  - Coordination of wing and whole-body development at developmental milestones
      ensures robustness against environmental and physiological perturbations.
AB  - Development produces correctly patterned tissues under a wide range of conditions
      that alter the rate of development in the whole body. We propose two hypotheses
      through which tissue patterning could be coordinated with whole-body development
      to generate this robustness. Our first hypothesis states that tissue patterning
      is tightly coordinated with whole-body development over time. The second
      hypothesis is that tissue patterning aligns at developmental milestones. To
      distinguish between our two hypotheses, we developed a staging scheme for the
      wing imaginal discs of Drosophila larvae using the expression of canonical
      patterning genes, linking our scheme to three whole-body developmental events:
      moulting, larval wandering and pupariation. We used our scheme to explore how the
      progression of pattern changes when developmental time is altered either by
      changing temperature or by altering the timing of hormone synthesis that drives
      developmental progression. We found the expression pattern in the wing disc
      always aligned at moulting and pupariation, indicating that these key
      developmental events represent milestones. Between these milestones, the
      progression of pattern showed greater variability in response to changes in
      temperature and alterations in physiology. Furthermore, our data showed that
      discs from wandering larvae showed greater variability in patterning stage. Thus
      for wing disc patterning, wandering does not appear to be a developmental
      milestone. Our findings reveal that tissue patterning remains robust against
      environmental and physiological perturbations by aligning at developmental
      milestones. Furthermore, our work provides an important glimpse into how the
      development of individual tissues is coordinated with the body as a whole. 

PMID- 24945256
TI  - Pri-miR-124 rs531564 and pri-miR-34b/c rs4938723 polymorphisms are associated
      with decreased risk of esophageal squamous cell carcinoma in Chinese populations.
AB  - MicroRNAs are a new class of small non-protein-coding RNAs that sometimes
      function as tumor suppressors or oncogenes. Aberrant expression and structural
      alteration of microRNAs have been reported to be involved in tumorigenesis and
      cancer development. Recently, rs531564/pri-miR-124-1, rs4938723/pri-miR-34b/c,
      rs7372209/pri-miR-26a-1, rs895819/pre-miR-27a, and rs11134527/pri-miR-218 were
      reported to be associated with risks of various cancers. In order to evaluate the
      relationship of these SNPs and esophageal squamous cell carcinoma (ESCC) risk, we
      conducted a case-control study with 1109 ESCC patients and 1275 control subjects
      to examine the potential association of these pri/pre-miRNA polymorphisms with
      ESCC susceptibility. As a result, two SNPs were associated with a significant
      risk of ESCC. We found that the GG genotype of pri-miR-124-1 rs531564 was
      associated to a significantly decreased risk of ESCC comparing with the CC/CG
      genotypes (p = 0.005; OR = 0.61, 95% CI = 0.43-0.86). In addition, the CC
      genotype of pri-miR-34b/c rs4938723 was associated with a significant decreased
      risk of ESCC (CC VS. TT/TC: p = 0.007, OR = 0.82, 95% CI = 0.71-0.95) in Chinese
      population. The present study provides the first evidence that pri-miR-124-1
      rs531564 and pri-miR-34 rs4938723 were associated with the risk of ESCC in
      Chinese population.

PMID- 24945257
TI  - Correlation between the glycan variations and defibrinogenating activities of
      acutobin and its recombinant glycoforms.
AB  - Acutobin isolated from Deinagkistrodon acutus venom has been used to prevent or
      treat stroke in patients. This defibrinogenating serine protease is a 39 kDa
      glycoprotein containing terminal disialyl-capped N-glycans. After sialidase
      treatment, the enzyme showed similar catalytic activities toward chromogenic
      substrate, and cleaved the Aalpha chain of fibrinogen as efficiently as the
      native acutobin did. However, the level of fibrinogen degradation products in
      mice after i.p.-injection of desialylated-acutobin was significantly lower than
      the level after acutobin injection, suggesting that the disialyl moieties may
      improve or prolong the half-life of acutobin. Two recombinant enzymes with
      identical protein structures and similar amidolytic activities to those of native
      acutobin were expressed from HEK293T and SW1353 cells and designated as HKATB and
      SWATB, respectively. Mass spectrometric profiling showed that their glycans
      differed from those of acutobin. In contrast to acutobin, HKATB cleaved not only
      the Aalpha chain but also the Bbeta and gamma chains of human fibrinogens, while
      SWATB showed a reduced alpha-fibrinogenase activity. Non-denaturing
      deglycosylation of these proteases by peptide N-glycosidase F significantly
      reduced their fibrinogenolytic activities and thermal stabilities. The in vivo
      defibrinogenating effect of HKATB was inferior to that of acutobin in mice. Taken
      together, our results suggest that the conjugated glycans of acutobin are
      involved in its interaction with fibrinogen, and that the selection of cells
      optimally expressing efficient glycoforms and further glycosylation engineering
      are desirable before a recombinant product can replace the native enzyme for
      clinical use. 

PMID- 24945260
TI  - Experiences of ethical issues when caring for children with cancer.
AB  - BACKGROUND: The treatment for pediatric cancer is often physically, socially, and
      psychologically demanding and often gives rise to ethical issues. OBJECTIVE: The
      purpose of this study was to describe healthcare professionals' experiences of
      ethical issues and ways to deal with these when caring for children with cancer.
      METHODS: A study-specific questionnaire was given to healthcare professionals at
      a pediatric hospital in Sweden. Qualitative content analysis was used to analyze
      answers to open-ended questions. The data were sorted into 2 domains based on the
      objective of the study. In the next step, the data in each domain were
      inductively coded, generating categories and subcategories. RESULTS: The main
      ethical issues included concerns of (1) infringing on autonomy, (2) deciding on
      treatment levels, and (3) conflicting perspectives that constituted a challenge
      to collaboration. Professionals desired teamwork and reflection to deal with
      ethical concerns, and they needed resources for dealing with ethics. IMPLICATIONS
      FOR PRACTICE: Interprofessional consideration needs to be improved. Forums and
      time for ethics reflections need to be offered to deal with ethical concerns in
      childhood cancer care. CONCLUSIONS: Experiences of ethical concerns and dealing
      with these in caring for children with cancer evoked strong feelings and moral
      perplexity among nursing staff. The study raises a challenging question: How can
      conflicting perspectives, lack of interprofessional consideration, and obstacles
      related to parents' involvement be "turned around," that is, contribute to a
      holistic perspective of ethics in cancer care of children?

PMID- 24945254
TI  - Comparative effects of n-3, n-6 and n-9 unsaturated fatty acid-rich diet
      consumption on lupus nephritis, autoantibody production and CD4+ T cell-related
      gene responses in the autoimmune NZBWF1 mouse.
AB  - Mortality from systemic lupus erythematosus (SLE), a prototypical autoimmune
      disease, correlates with the onset and severity of kidney glomerulonephritis.
      There are both preclinical and clinical evidence that SLE patients may benefit
      from consumption of n-3 polyunsaturated fatty acids (PUFA) found in fish oil, but
      the mechanisms remain unclear. Here we employed the NZBWF1 SLE mouse model to
      compare the effects of dietary lipids on the onset and severity of autoimmune
      glomerulonephritis after consuming: 1) n-3 PUFA-rich diet containing
      docosahexaenoic acid-enriched fish oil (DFO), 2) n-6 PUFA-rich Western-type diet
      containing corn oil (CRN) or 3) n-9 monounsaturated fatty acid (MUFA)-rich
      Mediterranean-type diet containing high oleic safflower oil (HOS). Elevated
      plasma autoantibodies, proteinuria and glomerulonephritis were evident in mice
      fed either the n-6 PUFA or n-9 MUFA diets, however, all three endpoints were
      markedly attenuated in mice that consumed the n-3 PUFA diet until 34 wk of age. A
      focused PCR array was used to relate these findings to the expression of 84 genes
      associated with CD4+ T cell function in the spleen and kidney both prior to and
      after the onset of the autoimmune nephritis. n-3 PUFA suppression of autoimmunity
      in NZBWF1 mice was found to co-occur with a generalized downregulation of CD4+ T
      cell-related genes in kidney and/or spleen at wk 34. These genes were associated
      with the inflammatory response, antigen presentation, T cell activation, B cell
      activation/differentiation and leukocyte recruitment. Quantitative RT-PCR of
      representative affected genes confirmed that n-3 PUFA consumption was associated
      with reduced expression of CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF
      alpha and osteopontin mRNAs in kidney and/or spleens as compared to mice fed n-6
      PUFA or n-9 MUFA diets. Remarkably, many of the genes identified in this study
      are currently under consideration as biomarkers and/or biotherapeutic targets for
      SLE and other autoimmune diseases. 

PMID- 24945261
TI  - Factorial structure of a scale: Strategies Used by People to Promote Health-
      Chinese version.
AB  - BACKGROUND: The Strategies Used by People to Promote Health (SUPPH) is an
      instrument used to measure self-reported self-efficacy in patient populations.
      Self-efficacy has a major impact on quality of life and psychological well-being.
      Previous findings of dimensionality of the SUPPH vary, and cultural differences
      exist suggesting the need for further investigation and psychometric testing to
      establish construct validity of the SUPPH in different cultures. OBJECTIVE: The
      purpose of this study was to examine the factorial structure of the Chinese
      version of the SUPPH (C-SUPPH). METHODS: Using reports from 764 oncology patients
      in China, the factorial structure of the C-SUPPH was assessed via 2 analytical
      strategies. First-order confirmatory factor analysis (CFA) models were used to
      examine the dimensionality of the C-SUPPH; a second-order CFA was used to
      determine the existence of a factorial structure hierarchy of the C-SUPPH.
      RESULTS: Compared with the 2- and 4-factor solutions, the 3-factor CFA of the C
      SUPPH had a better fit with the data (comparative fit index = 0.94, Tucker-Lewis
      index = 0.94, root-mean-square error of approximation = 0.05, the close-fit test
      P = .565, and standardized root-mean-square residual = 0.04). Our findings
      confirmed the 3-scale structure: Positive Attitude, Stress Reduction, and Making
      Decisions; together, the 3 factors represent an underlying higher-order factor,
      that of general self-care self-efficacy. CONCLUSIONS: The C-SUPPH has a valid
      factorial structure and can be readily applied to studying self-efficacy in
      Chinese patients who are diagnosed with cancers. IMPLICATIONS FOR PRACTICE: Our
      findings provide support for a culturally sensitive, reliable, and valid self
      efficacy measure (the C-SUPPH) of Chinese adult cancer patients' self-care self
      efficacy.

PMID- 24945262
TI  - Cancer fear and fatalism: how African American participants construct the role of
      research subject in relation to clinical cancer research.
AB  - BACKGROUND: Lack of African American participation in cancer clinical trials has
      been identified as a critical problem. Historical interactions related to race,
      identity, and power may contribute to continued inequity in healthcare and
      research participation. OBJECTIVE: The aim of this study was to explore the
      perceptions of African Americans regarding cancer and research and how these
      perceptions shape their beliefs about participating as cancer research subjects.
      METHODS: Three African American focus groups were conducted including people who
      had never participated in cancer research, those who had, and those who were
      asked but refused (n = 16). Discussion focused on their perceptions of cancer
      research and actual or potential participation as research subjects. Data were
      coded using both structured and inductive coding methods. RESULTS: Fear and
      fatalism emerged in relation to research, race, power, and identity and were
      related to larger historical and social issues rather than only individual
      thoughts or feelings. Participants described fears of the unknown, death,
      mistrust, conspiracy, and discrimination together with positive/negative tensions
      between self, family, and community responsibilities. CONCLUSION: Complex
      identities linked perceptions of cancer and cancer research with broader
      historical and cultural issues. Fear, fatalism, and current and historical
      relationships influence how people perceive themselves as research subjects and
      may influence their decisions to participate in cancer research. IMPLICATION FOR
      PRACTICE: Acknowledging how complex factors including race and racism contribute
      to health disparities may give nurses and other healthcare providers a better
      appreciation of how historical, social, and cultural dynamics at individual,
      community, and organizational levels influence access to and participation in
      cancer research.

PMID- 24945263
TI  - Women's perceptions of their lifestyle and quality of life several years after a
      diagnosis of endometrial cancer.
AB  - BACKGROUND: Few studies have examined the long-term changes experienced by women
      treated for endometrial cancer. OBJECTIVE: The objectives of this study were to
      describe what women perceived important to their lifestyle and quality of life in
      the years following their diagnosis and to provide new insights that might inform
      healthcare practice. METHODS: This was a thematic analysis of 237 open-ended
      comments from Australian women diagnosed with endometrial cancer 3 to 5 years
      previously. RESULTS: We identified 3 main themes: (1) personal change, in which
      women spoke about cancer as permanently altering their lives in mostly negative
      but sometimes positive ways; (2) continuity of former life, which described both
      the minimal impact of cancer on women's lives and identities and the difficulties
      negotiating this within the dominant "cancer survivorship" culture; (3) social
      support, where women wrote about how the quality of their relationships shaped
      their cancer trajectory. CONCLUSIONS: While typical "survivorship" issues exist
      for many women with endometrial cancer (eg, physical, emotional, sexual health
      changes), a proportion of women will not be focused on their cancer and can be
      encouraged to form lives and identities that are not situated within the "cancer
      survivorship" culture. IMPLICATIONS FOR PRACTICE: A network of support, sensitive
      to women's responses to having cancer, may benefit women's long-term adjustment.
      Regular standardized assessment of women's needs may facilitate appropriate
      support for those with concerns, whereas those without concerns could be
      reassured by health professionals that their experience is normal and shared by
      other people with cancer. This may encourage women to form lives that are
      personally meaningful.

PMID- 24945264
TI  - Facebook advertisements recruit parents of children with cancer for an online
      survey of web-based research preferences.
AB  - BACKGROUND: Studies involving samples of children with life-threatening illnesses
      and their families face significant challenges, including inadequate sample sizes
      and limited diversity. Social media recruitment and Web-based research methods
      may help address such challenges yet have not been explored in pediatric cancer
      populations. OBJECTIVE: This study examined the feasibility of using Facebook
      advertisements to recruit parent caregivers of children and teenagers with
      cancer. We also explored the feasibility of Web-based video recording in
      pediatric palliative care populations by surveying parents of children with
      cancer regarding (a) their preferences for research methods and (b) technological
      capabilities of their computers and phones. METHODS: Facebook's paid advertising
      program was used to recruit parent caregivers of children currently living with
      cancer to complete an electronic survey about research preferences and
      technological capabilities. RESULTS: The advertising campaign generated 3 897 981
      impressions, which resulted in 1050 clicks at a total cost of $1129.88. Of 284
      screened individuals, 106 were eligible. Forty-five caregivers of children with
      cancer completed the entire electronic survey. Parents preferred and had
      technological capabilities for Web-based and electronic research methods.
      Participant survey responses are reported. CONCLUSION: Facebook was a useful,
      cost-effective method to recruit a diverse sample of parent caregivers of
      children with cancer. Web-based video recording and data collection may be
      feasible and desirable in samples of children with cancer and their families.
      IMPLICATIONS FOR PRACTICE: Web-based methods (eg, Facebook, Skype) may enhance
      communication and access between nurses and pediatric oncology patients and their
      families.

PMID- 24945265
TI  - Uncertainty, Self-efficacy, and Self-care Behavior in Patients With Breast Cancer
      Undergoing Chemotherapy in China.
AB  - BACKGROUND: Treatment for breast cancer causes uncertainty in the face of new and
      distressing experiences and often results in the need for self-care. Identifying
      how uncertainty influences self-care behavior is essential to design
      interventions that enhance self-care capacity and improve patient outcomes.
      OBJECTIVES: The aims of this study were to describe the levels of uncertainty,
      self-efficacy, and self-care behavior in Chinese women receiving chemotherapy for
      breast cancer and to determine if self-efficacy mediates the relationship between
      uncertainty and self-care behavior. METHODS: A cross-sectional descriptive
      correlational design was used. Ninety-seven participants completed the
      Generalized Self-efficacy Scale, the Mishel Uncertainty in Illness Scale, and the
      Appraisal of Self-care Agency Scale-Revised. Descriptive statistics were used to
      analyze the levels of uncertainty, self-efficacy, and self-care behaviors in the
      sample. Multiple regression was used to test the mediating effect of self
      efficacy in the relationship between uncertainty and self-care behavior. RESULTS:
      Mean ratings of uncertainty (76.70), self-efficacy (27.15), and self-care
      behavior (53.96) all fell in the moderate range. Both uncertainty and self
      efficacy independently predicted self-care behavior, explaining 18.2% of the
      variance, but self-efficacy did not mediate the relationship between uncertainty
      and self-care behavior. CONCLUSIONS: Research is needed to further evaluate the
      proposed relationships using instruments specific to/related to cancer and
      evaluate change over time. Self-care interventions that have been efficacious in
      Western populations could be revised to assist Chinese women to reduce
      uncertainty and enhance self-efficacy in coping with breast cancer. IMPLICATIONS
      FOR PRACTICE: Self-care intervention programs should include strategies to reduce
      uncertainty and enhance self-efficacy in coping with breast cancer treatment.

PMID- 24945266
TI  - Relationships of Circadian Rhythms and Physical Activity With Objective Sleep
      Parameters in Lung Cancer Patients.
AB  - BACKGROUND: Lung cancer patients undergo various treatments leading to sleep
      problems, rest-activity circadian rhythms disruption, and reduced levels of
      physical activity. It is important to understand the relationships among these
      variables. Appropriate interventions can possibly be implemented to improve sleep
      quality in lung cancer patients. OBJECTIVE: The objective of this study was to
      examine the relationships of circadian rhythms and physical activity with
      objective sleep parameters in 106 of Taiwanese lung cancer patients. METHODS:
      This study used a cross-sectional design. The instruments included an actigraph
      to measure the objective sleep parameters (total sleep time [TST], sleep
      efficiency, and sleep-onset latency [SOL]), rest-activity circadian rhythms (r24
      [24-hour autocorrelation coefficient] and I < O [in-bed less than out-of-bed
      dichotomy index]), and physical activity frequency (UP activity mean). The daily
      physical activity amount in minutes was measured by the Bouchard 3-day physical
      activity record. RESULTS: Patients performing light-intensity physical activity
      of 295 min/d or greater had better values for the TST, sleep efficiency, SOL,
      r24, and I < O than those performing less than 295 min/d (all P < .05).
      Significant predictors of the TST included age (beta = -.31), I < O (beta = .32),
      and UP activity mean (beta = -.42). Predictors of the SOL included current
      treatment (beta = .20), I < O (beta = -.28), UP activity mean (beta = .51), and
      24-hour light-activity minutes (beta = -.23). CONCLUSIONS: Marked circadian
      rhythms and adequate light-intensity physical activity may improve sleep quality
      in lung cancer patients. IMPLICATIONS FOR PRACTICE: Adequate light-intensity
      physical activity can be an effective intervention to improve sleep quality in
      lung cancer patients.

PMID- 24945268
TI  - Effectiveness and Acceptability of a Moisturizing Cream and a Barrier Cream
      During Radiation Therapy for Breast Cancer in the Tropics: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Inconsistent evidence about product effectiveness to prevent moist
      desquamation during radiation treatment and minimal research about the
      acceptability to patients of recommended products prompted this study. OBJECTIVE:
      This randomized controlled trial compared the effectiveness of 2 creams at
      minimizing the incidence of moist desquamation in a tropical setting and explored
      which product was most acceptable to patients receiving radiation treatment.
      METHODS: Participants (n = 255) were stratified according to breast or chest wall
      radiation treatment and randomly allocated to use a moisturizing or barrier
      cream. Nurses assessed radiation skin reactions weekly with a standardized
      grading system, and patients were telephoned 1 month after completing treatment
      for a final skin assessment. Participants completed an Acceptability Survey at
      similar times. RESULTS: At treatment completion, 15% of participants had moist
      desquamation. An additional 26% self-reported this at follow-up. Risk factors for
      moist desquamation included increased breast cup size and body mass index. The
      barrier cream significantly reduced the incidence of moist desquamation during
      treatment in patients receiving radiation to the chest wall (chi = 3.93, P =
      .047). Participants preferred the barrier cream over the moisturizer (chi = 5.81,
      P = .02) during treatment. CONCLUSIONS: This study identified a relatively high
      incidence of moist desquamation in patients receiving radiation therapy for
      breast cancer. Future patients will have information about product effectiveness
      in minimizing moist desquamation when choosing skin care products. IMPLICATIONS
      FOR PRACTICE: Structured discharge planning and patient education need to include
      information about factors that contribute to the likelihood of developing moist
      desquamation.

PMID- 24945267
TI  - Evidence-Based Self-care Guidelines for People Receiving Chemotherapy: Do They
      Reduce Symptom Burden and Psychological Distress?
AB  - BACKGROUND: Despite numerous evidence-based guidelines (EBGs) being developed to
      manage the symptom burden associated with cancer and chemotherapy, there is a
      paucity of research exploring their efficacy. OBJECTIVE: The aim of this study
      was to explore the effect of implementing EBGs to reduce the symptom burden and
      psychological distress of cancer patients requiring outpatient chemotherapy at an
      acute, tertiary care public hospital in Western Australia. METHODS: The study was
      conducted in 2 populations and stages, using action research to promote change.
      Stage 1 assessed prevalence; in stage 2, specific EBGs were implemented. Symptom
      prevalence, severity, and bother were determined at baseline and 1 week and 1
      month after initial chemotherapy, to allow comparison between stages. RESULTS:
      Stage 2 participants did better at managing feeling low (odds ratio, 2.33; 95%
      confidence interval, 1.47-3.70; P < .001) and vomiting (odds ratio, 2.37; 95%
      confidence interval, 1.13-4.97; P = .022). Bother was greater in stage 2 at
      baseline for vomiting (P = .040), pain (P = .017), feeling tired (P = .038),
      feeling anxious or worried (P = .001), and feeling low (P = .024). By 1 month,
      only feeling anxious or worried (P = .023) and feeling low (P = .006) differed.
      Severity was greater in stage 2 at baseline for pain (P = .025) and feeling
      anxious or worried (P = .008). By 1 month, only feeling anxious or worried (P =
      .010) differed. CONCLUSION: Effective self-care strategies to manage the adverse
      effects of chemotherapy should be evidence based but individualized, as our
      findings suggest; for some, focusing on their symptoms may not always be
      beneficial. IMPLICATIONS FOR PRACTICE: Providing patients with pathways to
      information as needed may be preferable to administering multiple EBGs.

PMID- 24945269
TI  - Quality of Life in African American Breast Cancer Survivors: An Integrative
      Literature Review.
AB  - BACKGROUND: The quality of life (QOL) of African American (AA) breast cancer
      survivors (BCSs) is poorer than that of non-Hispanic white BCSs. It is necessary
      to address factors related to poor QOL of AA women entering survivorship.
      Research addressing QOL in AA BCSs is inconsistent in measurements and methods.
      OBJECTIVE: The objective of this study was to synthesize factors contributing to
      QOL in AA breast cancer survivorship utilizing the model of Ferrell et al (1995).
      Research question was: Which factors are used in studies of QOL in AA breast
      cancer survivorship? REVIEW METHODS: This integrative literature review included
      studies exploring some aspect of QOL in AA BCSs. Studies were excluded that
      validated psychometric measures, did not report QOL, or did not explore AAs
      and/or BCSs as a separate group within the study. RESULTS: The search strategy
      yielded 240 references; 38 were retrieved, read, and rated for relevance and
      research quality. A set of 19 articles met relevance criteria. CONCLUSION: The
      review showed a lack of research exploring factors affecting spiritual and
      physical well-being domains, demonstrating a need for future research. In
      addition, the lack of community-based studies signals a need for community
      engagement in the research process, starting with spiritual leaders.
      IMPLICATIONS: Researchers must focus on factors from a multidomain perspective to
      truly understand the varied dimensions influencing QOL of AA BCSs.

PMID- 24945270
TI  - A tailored Web-based psychoeducational intervention for cancer patients and their
      family caregivers.
AB  - BACKGROUND: Most programs addressing psychosocial concerns of cancer survivors
      are in-person programs that are expensive to deliver, have limited availability,
      and seldom deal with caregivers' concerns. OBJECTIVE: This study examined the
      feasibility of translating an efficacious nurse-delivered program (FOCUS Program)
      for patients and their caregivers to a tailored, dyadic Web-based format.
      Specific aims were to (1) test the preliminary effects of the Web-based
      intervention on patient and caregiver outcomes, (2) examine participants' program
      satisfaction, and (3) determine the feasibility of using a Web-based delivery
      format. METHODS: A phase 2 feasibility study was conducted with cancer patients
      (lung, breast, colorectal, prostate) and their family caregivers (N = 38 dyads).
      The Web-based intervention provided information and support tailored to the
      unique characteristics of each patient, caregiver, and their dyadic relationship.
      Primary outcomes were emotional distress and quality of life. Secondary outcomes
      were benefits of illness/caregiving, communication, support, and self-efficacy.
      Analyses included descriptive statistics and repeated-measures analysis of
      variance. RESULTS: Dyads had a significant decrease in emotional distress,
      increase in quality of life, and perceived more benefits of illness/caregiving.
      Caregivers also had significant improvement in self-efficacy. There were no
      changes in communication. Participants were satisfied with program usability, but
      recommended additional content. CONCLUSIONS: It was possible to translate a
      clinician-delivered program to a Web-based format that was easy to use and had
      positive effects on dyadic outcomes. IMPLICATIONS FOR PRACTICE: The Web-based
      program is a promising way to provide psychosocial care to more patients and
      caregivers using fewer personnel. It needs further testing in a larger randomized
      clinical trial.

PMID- 24945271
TI  - IscR is essential for yersinia pseudotuberculosis type III secretion and
      virulence.
AB  - Type III secretion systems (T3SS) are essential for virulence in dozens of
      pathogens, but are not required for growth outside the host. Therefore, the T3SS
      of many bacterial species are under tight regulatory control. To increase our
      understanding of the molecular mechanisms behind T3SS regulation, we performed a
      transposon screen to identify genes important for T3SS function in the food-borne
      pathogen Yersinia pseudotuberculosis. We identified two unique transposon
      insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron
      sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion
      mutant (DeltaiscR) was deficient in secretion of Ysc T3SS effector proteins and
      in targeting macrophages through the T3SS. To determine the mechanism behind IscR
      control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis
      to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a
      putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF
      operon. As LcrF controls transcription of a number of critical T3SS genes in
      Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through
      LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and
      mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis
      in the absence of IscR. Importantly, mice orally infected with the Y.
      pseudotuberculosis DeltaiscR mutant displayed decreased bacterial burden in
      Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an
      essential role for IscR in Y. pseudotuberculosis virulence. This study presents
      the first characterization of Yersinia IscR and provides evidence that IscR is
      critical for virulence and type III secretion through direct regulation of the
      T3SS master regulator, LcrF. 

PMID- 24945273
TI  - HIV-1 diversity and drug-resistant mutations in infected individuals in
      Changchun, China.
AB  - OBJECTIVES: Human immunodeficiency virus type 1 (HIV-1) infection has been
      detected in all provinces of China. Although epidemiological and phylogenetic
      studies have been conducted in many regions, such analyses are lacking from Jilin
      province in northeastern China. METHOD: Epidemiological and phylogenetic
      analyses, as well as detection of drug-resistant mutations, were conducted on 57
      HIV-1 infected patients from Changchun city identified and confirmed through
      annual surveillance by local Centers for Disease Control in Jilin province of
      northeastern China in 2012. RESULTS: Sexual contact was determined to be the
      major pathway for HIV-1 transmission in Jilin, where hetero- and homosexual
      activities contributed almost equally. Phylogenetic analyses detected multiple
      subtypes of HIV-1 including subtype G circulating in Jilin, with multiple origins
      for each of them. Both subtype B and CRF01_AE were dominant, and evidence of
      subtype B transmitting between different high-risk groups was observed. Mutations
      in the viral protease at position 71 indicated the presence of a selective
      pressure. Several drug-resistant mutations were detected, although they were
      predicted with low-level resistance to antiviral treatments. CONCLUSIONS:
      Information from this study fills the gap in knowledge of HIV-1 transmission in
      Changchun city, Jilin province, China. By revealing the origin and evolutionary
      status of local HIV-1 strains, this work contributes to ongoing efforts in the
      control and prevention of AIDS.

PMID- 24945272
TI  - Regulation of Schistosoma mansoni development and reproduction by the mitogen
      activated protein kinase signaling pathway.
AB  - BACKGROUND: Protein kinases are proven targets for drug development with an
      increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as
      drugs. Mitogen-activated protein kinase (MAPK) family members connect cell
      surface receptors to regulatory targets within cells and influence a number of
      tissue-specific biological activities such as cell proliferation, differentiation
      and survival. However, the contributions of members of the MAPK pathway to
      schistosome development and survival are unclear. METHODOLOGY/PRINCIPAL FINDINGS:
      We employed RNA interference (RNAi) to elucidate the functional roles of five S.
      mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK
      signaling pathway. Mice were injected with post-infective larvae (schistosomula)
      subsequent to RNAi and the development of adult worms observed. The data
      demonstrate that SmJNK participates in parasite maturation and survival of the
      parasites, whereas SmERK are involved in egg production as infected mice had
      significantly lower egg burdens with female worms presenting underdeveloped
      ovaries. Furthermore, it was shown that the c-fos transcription factor was
      overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2
      indicating its putative involvement in gene regulation in this parasite's MAPK
      signaling cascade. CONCLUSIONS: We conclude that MAPKs proteins play important
      roles in the parasite in vivo survival, being essential for normal development
      and successful survival and reproduction of the schistosome parasite. Moreover
      SmERK and SmJNK are potential targets for drug development.

PMID- 24945275
TI  - The serine-threonine protein kinase PAK4 is dispensable in zebrafish:
      identification of a morpholino-generated pseudophenotype.
AB  - TALEN-based inactivation of the zebrafish pak4 gene resulted in embryos and adult
      fish that appear normal and fertile. This is in contrast to our previously
      published studies which were based on the use of antisense morpholino
      oligonucleotides (MOs). We have excluded potential explanations such as gene
      duplication, alternate splicing, cryptic initiation of translation, and
      translation-independent RNA function. Our conclusion is that pak4 is dispensable
      in zebrafish, and that even when corroborated by robust controls, such as RNA
      rescue, MOs may elicit misleading pseudophenotypes that do not correspond to
      results obtained by genetic mutations, and should thus be used with caution. 

PMID- 24945274
TI  - Contribution of specific residues of the beta-solenoid fold to HET-s prion
      function, amyloid structure and stability.
AB  - The [Het-s] prion of the fungus Podospora anserina represents a good model system
      for studying the structure-function relationship in amyloid proteins because a
      high resolution solid-state NMR structure of the amyloid prion form of the HET-s
      prion forming domain (PFD) is available. The HET-s PFD adopts a specific beta
      solenoid fold with two rungs of beta-strands delimiting a triangular hydrophobic
      core. A C-terminal loop folds back onto the rigid core region and forms a more
      dynamic semi-hydrophobic pocket extending the hydrophobic core. Herein, an
      alanine scanning mutagenesis of the HET-s PFD was conducted. Different structural
      elements identified in the prion fold such as the triangular hydrophobic core,
      the salt bridges, the asparagines ladders and the C-terminal loop were altered
      and the effect of these mutations on prion function, fibril structure and
      stability was assayed. Prion activity and structure were found to be very robust;
      only a few key mutations were able to corrupt structure and function. While some
      mutations strongly destabilize the fold, many substitutions in fact increase
      stability of the fold. This increase in structural stability did not influence
      prion formation propensity in vivo. However, if an Ala replacement did alter the
      structure of the core or did influence the shape of the denaturation curve, the
      corresponding variant showed a decreased prion efficacy. It is also the finding
      that in addition to the structural elements of the rigid core region, the
      aromatic residues in the C-terminal semi-hydrophobic pocket are critical for
      prion propagation. Mutations in the latter region either positively or negatively
      affected prion formation. We thus identify a region that modulates prion
      formation although it is not part of the rigid cross-beta core, an observation
      that might be relevant to other amyloid models. 

PMID- 24945277
TI  - Phenotype of transgenic mice carrying a very low copy number of the mutant human
      G93A superoxide dismutase-1 gene associated with amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of
      the motor neuron. While most cases of ALS are sporadic, 10% are familial (FALS)
      with 20% of FALS caused by a mutation in the gene that codes for the enzyme Cu/Zn
      superoxide dismutase (SOD1). There is variability in sporadic ALS as well as FALS
      where even within the same family some siblings with the same mutation do not
      manifest disease. A transgenic (Tg) mouse model of FALS containing 25 copies of
      the mutant human SOD1 gene demonstrates motor neuron pathology and progressive
      weakness similar to ALS patients, leading to death at approximately 130 days. The
      onset of symptoms and survival of these transgenic mice are directly related to
      the number of copies of the mutant gene. We report the phenotype of a very low
      expressing (VLE) G93A SOD1 Tg carrying only 4 copies of the mutant G93ASOD1 gene.
      While weakness can start at 9 months, only 74% of mice 18 months or older
      demonstrate disease. The VLE mice show decreased motor neurons compared to wild
      type mice as well as increased cytoplasmic translocation of TDP-43. In contrast
      to the standard G93A SOD1 Tg mouse which always develops motor weakness leading
      to death, not all VLE animals manifested clinical disease or shortened life span.
      In fact, approximately 20% of mice older than 24 months had no motor symptoms and
      only 18% of VLE mice older than 22 months reached end stage. Given the variable
      penetrance of clinical phenotype, prolonged survival, and protracted loss of
      motor neurons the VLE mouse provides a new tool that closely mimics human ALS.
      This tool will allow the study of pathologic events over time as well as the
      study of genetic and environmental modifiers that may not be causative, but can
      exacerbate or accelerate motor neuron disease. 

PMID- 24945276
TI  - Sgo1 regulates both condensin and Ipl1/Aurora B to promote chromosome
      biorientation.
AB  - Correct chromosome segregation is essential in order to prevent aneuploidy. To
      segregate sister chromatids equally to daughter cells, the sisters must attach to
      microtubules emanating from opposite spindle poles. This so-called biorientation
      manifests itself by increased tension and conformational changes across
      kinetochores and pericentric chromatin. Tensionless attachments are dissolved by
      the activity of the conserved mitotic kinase Aurora B/Ipl1, thereby promoting the
      formation of correctly attached chromosomes. Recruitment of the conserved
      centromeric protein shugoshin is essential for biorientation, but its exact role
      has been enigmatic. Here, we identify a novel function of shugoshin (Sgo1 in
      budding yeast) that together with the protein phosphatase PP2A-Rts1 ensures
      localization of condensin to the centromeric chromatin in yeast Saccharomyces
      cerevisiae. Failure to recruit condensin results in an abnormal conformation of
      the pericentric region and impairs the correction of tensionless chromosome
      attachments. Moreover, we found that shugoshin is required for maintaining Aurora
      B/Ipl1 localization on kinetochores during metaphase. Thus, shugoshin has a dual
      function in promoting biorientation in budding yeast: first, by its ability to
      facilitate condensin recruitment it modulates the conformation of the pericentric
      chromatin. Second, shugoshin contributes to the maintenance of Aurora B/Ipl1 at
      the kinetochore during gradual establishment of bipolarity in budding yeast
      mitosis. Our findings identify shugoshin as a versatile molecular adaptor that
      governs chromosome biorientation. 

PMID- 24945278
TI  - Neuronal expression of muscle LIM protein in postnatal retinae of rodents.
AB  - Muscle LIM protein (MLP) is a member of the cysteine rich protein family and has
      so far been regarded as a muscle-specific protein that is mainly involved in
      myogenesis and the organization of cytoskeletal structure in myocytes,
      respectively. The current study demonstrates for the first time that MLP
      expression is not restricted to muscle tissue, but is also found in the rat naive
      central nervous system. Using quantitative PCR, Western blot and
      immunohistochemical analyses we detected MLP in the postnatal rat retina,
      specifically in the somas and dendritic arbors of cholinergic amacrine cells (AC)
      of the inner nuclear layer and the ganglion cell layer (displaced AC). Induction
      of MLP expression started at embryonic day 20 and peaked between postnatal days 7
      and 14. It subsequently decreased again to non-detectable protein levels after
      postnatal day 28. MLP was identified in the cytoplasm and dendrites but not in
      the nucleus of AC. Thus, retinal MLP expression correlates with the morphologic
      and functional development of cholinergic AC, suggesting a potential role of this
      protein in postnatal maturation and making MLP a suitable marker for these
      neurons. 

PMID- 24945279
TI  - Aberrant expression and distribution of enzymes of the urea cycle and other
      ammonia metabolizing pathways in dogs with congenital portosystemic shunts.
AB  - The detoxification of ammonia occurs mainly through conversion of ammonia to urea
      in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic
      shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic
      encephalopathy. In this study, the gene expression of urea cycle enzymes
      (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC),
      argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase
      (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and
      glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after
      surgical closure of the shunt. Additionally, immunohistochemistry was performed
      on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with
      CPSS to investigate a possible zonal distribution of these enzymes within the
      liver lobule and to investigate possible differences in distribution in dogs with
      CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia
      concentrations on the expression of the urea cycle enzymes was investigated in
      primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS
      was down regulated in dogs with CPSS and did not normalize after surgical closure
      of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1,
      OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs,
      these enzymes lacked a clear zonal distribution. In primary hepatocytes higher
      ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the
      reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the
      alterations in zonal distribution in dogs with CPSS may be caused by a
      developmental arrest of these enzymes during the embryonic or early postnatal
      phase. 

PMID- 24945282
TI  - Behaviors and strategies of bacterial navigation in chemical and nonchemical
      gradients.
AB  - Navigation of cells to the optimal environmental condition is critical for their
      survival and growth. Escherichia coli cells, for example, can detect various
      chemicals and move up or down those chemical gradients (i.e., chemotaxis). Using
      the same signaling machinery, they can also sense other external factors such as
      pH and temperature and navigate from both sides toward some intermediate levels
      of those stimuli. This mode of precision sensing is more sophisticated than the
      (unidirectional) chemotaxis strategy and requires distinctive molecular
      mechanisms to encode and track the preferred external conditions. To
      systematically study these different bacterial taxis behaviors, we develop a
      continuum model that incorporates microscopic signaling events in single cells
      into macroscopic population dynamics. A simple theoretical result is obtained for
      the steady state cell distribution in general. In particular, we find the cell
      distribution is controlled by the intracellular sensory dynamics as well as the
      dependence of the cells' speed on external factors. The model is verified by
      available experimental data in various taxis behaviors (including bacterial
      chemotaxis, pH taxis, and thermotaxis), and it also leads to predictions that can
      be tested by future experiments. Our analysis help reveal the key
      conditions/mechanisms for bacterial precision-sensing behaviors and directly
      connects the cellular taxis performances with the underlying molecular
      parameters. It provides a unified framework to study bacterial navigation in
      complex environments with chemical and non-chemical stimuli. 

PMID- 24945280
TI  - Viral etiologies of hospitalized acute lower respiratory infection patients in
      China, 2009-2013.
AB  - BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of
      acute illnesses and mortality worldwide and in China. However, a large-scale
      study on the prevalence of viral infections across multiple provinces and seasons
      has not been previously reported from China. Here, we aimed to identify the viral
      etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS:
      Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in
      24 provinces of China was conducted from January 2009-September 2013. We enrolled
      hospitalized all-age patients with ALRI, and collected respiratory specimens,
      blood or serum collected for diagnostic testing for respiratory syncytial virus
      (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus
      (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus
      (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals
      in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one
      etiology. The most frequently detected virus was RSV (9.9%), followed by
      influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV
      (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common
      etiology (17.0%) in young children aged <2 years. Influenza viruses were the main
      cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were
      more frequent in children, while hCoV infection was distributed evenly in all
      age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV
      infections. CONCLUSIONS: Our findings could serve as robust evidence for public
      health authorities in drawing up further plans to prevent and control ALRIs
      associated with viral pathogens. RSV is common in young children and prevention
      measures could have large public health impact. Influenza was most common in
      adults and influenza vaccination should be implemented on a wider scale in China.

PMID- 24945283
TI  - Gd3+ and calcium sensitive, sodium leak currents are features of weak membrane
      glass seals in patch clamp recordings.
AB  - The properties of leaky patch currents in whole cell recording of HEK-293T cells
      were examined as a means to separate these control currents from expressed sodium
      and calcium leak channel currents from snail NALCN leak channels possessing both
      sodium (EKEE) and calcium (EEEE) selectivity filters. Leak currents were
      generated by the weakening of gigaohm patch seals by artificial membrane rupture
      using the ZAP function on the patch clamp amplifier. Surprisingly, we found that
      leak currents generated from the weakened membrane/glass seal can be surprisingly
      stable and exhibit behavior that is consistent with a sodium leak current derived
      from an expressible channel. Leaky patch currents differing by 10 fold in size
      were similarly reduced in size when external sodium ions were replaced with the
      large monovalent ion NMDG+. Leaky patch currents increased when external Ca2+
      (1.2 mM) was lowered to 0.1 mM and were inhibited (>40% to >90%) with 10 uM Gd3+,
      100 uM La3+, 1 mM Co2+ or 1 mM Cd2+. Leaky patch currents were relatively
      insensitive (<30%) to 1 mM Ni2+ and exhibited a variable amount of block with 1
      mM verapamil and were insensitive to 100 uM mibefradil or 100 uM nifedipine. We
      hypothesize that the rapid changes in leak current size in response to changing
      external cations or drugs relates to their influences on the membrane seal
      adherence and the electro-osmotic flow of mobile cations channeling in crevices
      of a particular pore size in the interface between the negatively charged patch
      electrode and the lipid membrane. Observed sodium leak conductance currents in
      weak patch seals are reproducible between the electrode glass interface with cell
      membranes, artificial lipid or Sylgard rubber. 

PMID- 24945285
TI  - Pulsed radiofrequency treatment of complex regional pain syndrome: a case series.
AB  - BACKGROUND: Various forms of sympathetic chain neurolysis (sympathectomy) have,
      at one time or another, held promise as effective treatment options for complex
      regional pain syndrome (CRPS). Complications, such as worsening pain and the
      development of new pain syndromes, have prevented sympathectomy from emerging as
      a standard intervention. In an effort to avoid poor outcomes associated with
      neurolysis, pulsed radiofrequency (PRF) has been proposed as a potential
      treatment alternative for a number of chronic neuropathic pain states, including
      some forms of CRPS. METHODS: The present report describes three cases in which
      patients diagnosed with lower extremity CRPS type I obtained substantial and
      lasting intervals of pain relief following PRF of the lumbar sympathetic chain.
      Over a period of four years, 14 fluoroscopically guided procedures using PRF
      lesioning of the lumbar sympathetic chain at L2, L3 and L4 were performed in
      three individuals with CRPS type I of the lower limb. Outcome measures included
      pre- and post-treatment self-reported pain and medication requirements. RESULTS:
      Substantial pain relief (>50%) was achieved in 91.7% of PRF applications at three
      months and 83.3% at six months, with some treatments resulting in persistent
      relief well beyond 12 months. Medication use decreased to a comparable degree,
      with discontinuation of opiates after all but three treatments. CONCLUSIONS: PRF
      lesioning of the lumbar sympathetic chain can be an effective treatment for
      patients with CRPS type I of the lower extremity, with the potential to provide
      >=6 months of substantial pain relief.

PMID- 24945284
TI  - Clinical and parasitological protection in a Leishmania infantum-macaque model
      vaccinated with adenovirus and the recombinant A2 antigen.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a severe vector-born disease of humans
      and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to
      0.4 million new human VL cases occur annually worldwide. In the new world, these
      alarming numbers are primarily due to the impracticality of current control
      methods based on vector reduction and dog euthanasia. Thus, a prophylactic
      vaccine appears to be essential for VL control. The current efforts to develop an
      efficacious vaccine include the use of animal models that are as close to human
      VL. We have previously reported a L. infantum-macaque infection model that is
      reliable to determine which vaccine candidates are most worthy for further
      development. Among the few amastigote antigens tested so far, one of specific
      interest is the recombinant A2 (rA2) protein that protects against experimental
      L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates
      were vaccinated using three rA2-based prime-boost immunization regimes: three
      doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum
      (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector
      encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5
      A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two
      doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious
      challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as
      animals responded with increased pre-challenge production of anti-A2-specific IgG
      antibodies, though with some variability in the response, depending on the
      vaccine formulation/protocol. The relative parasite load in the liver was
      significantly lower in immunized macaques as compared to controls. Protection
      correlated with hepatic granuloma resolution, and reduction of clinical symptoms,
      particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum
      protocol. CONCLUSIONS/SIGNIFICANCE: The remarkable clinical protection induced by
      A2 in an animal model that is evolutionary close to humans qualifies this antigen
      as a suitable vaccine candidate against human VL.

PMID- 24945286
TI  - Does low-level laser therapy enhance the efficacy of intravenous regional
      anesthesia?
AB  - BACKGROUND: The use of intravenous regional anesthesia (IVRA) is limited by pain
      resulting from the application of tourniquets and postoperative pain. OBJECTIVE:
      To assess the efficacy of low-level laser therapy added to IVRA for improving
      pain related to surgical fixation of distal radius fractures. METHODS: The
      present double-blinded, placebo-controlled, randomized clinical trial involved 48
      patients who were undergoing surgical fixation of distal radius fractures.
      Participants were randomly assigned to either an intervention group (n=24), who
      received 808 nm laser irradiation as 4 J/point for 20 s over ipsilateral three
      nerve roots in the cervical region corresponding to C5-C8 vertebrae, and 808 nm
      laser irradiation as 0.1 J/cm2 for 5 min in a tangential scanning mode over the
      affected extremity; or a control group (n=24), who underwent the same protocol
      and timing of laser probe application with the laser switched off. Both groups
      received the same IVRA protocol using 2% lidocaine. RESULTS: The mean visual
      analogue scale scores were significantly lower in the laser-assisted group than
      in the lidocaine-only group on all measurements during and after operation
      (P<0.05). The mean time to the first need for fentanyl administration during the
      operation was longer in the laser group (P=0.04). The total amount of fentanyl
      administered to patients was significantly lower in the laser-assisted group
      (P=0.003). The laser group needed significantly less pethidine for pain relief
      (P=0.001) and at a later time (P=0.002) compared with the lidocaine-only group.
      There was no difference between the groups in terms of mean arterial pressure and
      heart rate. CONCLUSION: The addition of gallium-aluminum-arsenide laser
      irradiation to intravenous regional anesthesia is safe, and reduces pain during
      and after the operation.

PMID- 24945287
TI  - A prospective study of percutaneous vertebroplasty for chronic painful
      osteoporotic vertebral compression fracture.
AB  - BACKGROUND: Percutaneous vertebroplasty (PVP) for patients with chronic painful
      osteoporotic compression fractures has not been extensively studied. OBJECTIVE:
      To prospectively evaluate the efficacy of PVP for patients with chronic painful
      osteoporotic vertebral compression fractures (VCFs). METHODS: Sixty-two
      consecutive patients with chronic painful osteoporotic VCFs for >=3 months
      underwent PVP. All procedures were performed under local anesthesia. The outcomes
      were pain relief at one week, one month, three months, six months and one year,
      as measured by visual analogue scale, Oswestry Disability Index, Quality of Life
      Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and Roland
      Morris Disability Questionnaire scores. RESULTS: The PVP procedures were
      technically successful and well tolerated in all patients. Sixty-two patients
      underwent PVP on 92 vertebrae in 73 procedures three to five days after referral,
      and no 30-day mortality was observed. Compared with baseline scores, improvement
      in visual analogue scale, Oswestry Disability Index, QUALEFFO and Roland Morris
      Disability Questionnaire scores was significantly greater after PVP at one week
      (P<0.001), one month (P<0.001), three months (P<0.001), six months (P<0.001) and
      one year (P<0.001), and the number of patients using drugs for pain treatment was
      significantly reduced. Five new fractures were reported in five of 62 patients
      treated with PVP during follow-up. CONCLUSION: PVP is effective in patients with
      chronic painful osteoporotic VCFs. Pain relief after PVP was immediate, was
      sustained for one year and may be an important factor for reducing persistent
      pain.

PMID- 24945288
TI  - Factors predicting adverse events associated with pregabalin administered for
      neuropathic pain relief.
AB  - BACKGROUND: Pregabalin administration is occasionally abandoned due to adverse
      events such as somnolence, dizziness, unsteadiness, weight gain and edema.
      However, the exact causes of these differences in adverse events associated with
      pregabalin have not been elucidated. OBJECTIVE: To identify factors predicting
      adverse events associated with pregabalin administered for neuropathic pain.
      METHODS: The present study was a retrospective analysis involving 208 patients
      with neuropathic pain who had been treated with pregabalin in the pain clinic at
      the authors' hospital between July 2010 and September 2011. Variables were
      extracted from the clinical records for regression analysis of factors related to
      the occurrence of adverse events associated with pregabalin administration.
      Multivariate logistic regression analysis was used to examine the relationship
      between various predictive factors and the adverse events. RESULTS: Predictive
      factors were: duration of therapy (OR 1.684 [95% CI 1.179 to 2.406]; P=0.0042)
      for somnolence; nonsteroidal anti-inflammatory drugs (OR 0.132 [95% CI 0.030 to
      0.578]; P=0.0072), age (OR 3.137 [95% CI 1.220 to 8.066]; P=0.0177) and
      maintenance dose (OR 0.437 [95% CI 0.217 to 0.880]; P=0.0205) for unsteadiness;
      serum creatinine (OR 6.439 [95% CI 1.541 to 26.902]; P=0.0107) for body weight
      gain; and neurotropin (OR 8.538 [95% CI 1.159 to 62.901]; P=0.0353) and serum
      creatinine (OR 6.912 [95% CI 1.118 to 42.726]; P=0.0375) for edema. CONCLUSIONS:
      The results of the present study indicate that care is warranted regarding long
      durations of therapy for somnolence, advanced age rather than dose-dependent
      adverse events for unsteadiness, elevated serum creatinine level for weight gain,
      and elevated serum creatinine level and combination use of neurotropin for edema.
      The safety of the combined use of pregabalin and nonsteroidal anti-inflammatory
      drugs were also suggested.

PMID- 24945289
TI  - Breakthrough pain in patients with controlled or uncontrolled basal pain: an
      observational study.
AB  - BACKGROUND: Breakthrough pain (BTP) is traditionally defined as a pain
      exacerbation in patients with chronic controlled pain. However, this definition
      has recently been challenged. OBJECTIVES: To evaluate the prevalence of
      unsatisfactory control in patients with chronic cancer pain, and investigate the
      frequency and intensity of BTP episodes. METHODS: A total of 665 patients with
      chronic cancer pain attending 21 pain therapy units in Italy were evaluated for
      baseline pain intensity and number of BTP episodes over a 30-day period. All
      patients started, continued or modified treatment for BTP at enrollment,
      according to medical judgment. RESULTS: The number of BTP events was higher in
      patients with uncontrolled baseline pain, although the intensity and duration of
      episodes were similar. In patients with uncontrolled baseline pain, the number of
      events decreased with time and reached values comparable with those reported in
      patients with controlled pain. Both the intensity of the pain and the duration of
      the BTP events exhibited similar values in the two groups at all time points,
      following increased monitoring and the prescription of analgesic medication.
      CONCLUSION: Patients with uncontrolled baseline pain experienced BTP flares with
      higher frequency, but similar intensity and duration with respect to patients
      with controlled pain at baseline. Notably, a close follow-up and adequate
      management of the BTP episodes led to an improvement of BTP in the observed
      patients.

PMID- 24945290
TI  - Perioperative and long-term clinical outcomes for bone morphogenetic protein
      versus iliac crest bone graft for lumbar fusion in degenerative disk disease:
      systematic review with meta-analysis.
AB  - STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To compare the
      perioperative and long-term postoperative effectiveness of bone morphogenetic
      protein (BMP) for lumbar arthrodesis in skeletally mature adults with
      degenerative disk disease (DDD) to that of the current golden standard treatment,
      iliac crest autologous bone graft (ICBG). SUMMARY OF BACKGROUND DATA: The
      treatment efficacy of lumbar arthrodesis in DDD is a complex clinical and
      economic issue for patients and health care providers. METHODS: Comprehensive
      electronic literature search was performed using following databases: Ovid
      MEDLINE; Embase; Cochrane Library; Central Register of Controlled Trials
      (CENTRAL); Database of Abstracts of Reviews of Effects; Methodology Register;
      Technology Assessment Database; and Economic Evaluation Database. The full year
      ranges of each database until May of 2012 were included. RESULTS: Eight
      randomized controlled clinical trials of 383 citations were selected. The
      included studies involved 1138 participants. The pooled 2-year postoperative
      clinical outcomes were equivalent in BMP and ICBG groups, and exceeded minimum
      clinically important differences for Oswestry Disability Index, SF-36 (physical
      scale), and numeric rating scale (back pain). ICBG was associated with increased
      pain and complications at the donor site (P<0.01). The pooled average operative
      time was 21 minutes less in BMP versus ICBG (P<0.001). The pooled rate of
      additional surgical treatment was 2 times less in the BMP than in the ICBG groups
      (P=0.006). The pooled risk of nonunion at 24-month follow-up was 2 times less in
      the BMP than in the ICBG groups (P=0.037), however, this effect was likely
      biased. CONCLUSIONS: BMP, in particular rhBMP-2, is a good alternative to
      autogenous bone graft, especially in cases when harvesting of autologous bone is
      contraindicated or undesirable, operation time is limited, and there are no
      contraindications for BMP use.However, the current study did not reveal evidence
      robust enough to develop strong medical recommendations concerning BMP use for
      lumbar arthrodesis in degenerative disk disease.

PMID- 24945291
TI  - Clinical and computed tomographic evaluation of safety and efficacy of facet
      screw fixation in the subaxial cervical spine.
AB  - DESIGN: A retrospective study comparing screw positioning and associated
      complications between 2 different facet screw placement methods. OBJECTIVE: To
      review the anatomic location, clinical safety, efficacy, and limitations of 2
      facet screw placement techniques. BACKGROUND: Facet screw fixation in the
      subaxial cervical spine penetrates 4 cortical layers and affords better stability
      than lateral mass screws. Takayasu and colleagues recommended placing screws in
      the sagittal plane. We modified the trajectory to direct the screws laterally
      from the sagittal plane to place the root at less risk and improve fixation by
      increasing the excursion of the screws into bone. No clinical reports exist
      describing the quadricortical facet screw placed in a lateral direction. METHODS:
      A total of 95 screws were used in 18 consecutive patients who underwent posterior
      cervical stabilization for various spinal disorders: 34 screws used sagittal
      plane screw placement and 61 used our technique. Screw-related complications were
      reviewed. Screw trajectories and screw tip positions related to the ventral
      cortical margin and vertebral artery were evaluated using postoperative 3
      dimensional computed tomograms taken within 6 months after surgery.
      Instrumentation failures were evaluated from postoperative 3-dimensional computed
      tomograms taken 2 years after surgery. RESULTS: There was 1 complication, nerve
      root irritation due to screw malposition. Postoperative computed tomographic
      images revealed that drilling was 30 degrees lateral from the sagittal plane in
      our method. Fourth cortex penetration failed in 29% of the screws placed in the
      sagittal plane and in 5% by our method. Screw loosening was significantly
      increased using screws placed in the sagittal plane (24% vs. 2%). CONCLUSIONS:
      Quadricortical facet screw placement aimed at the juncture between the transverse
      process and the facet is practicable. Screw loosening was significantly reduced
      using this lateral screw direction. One of the disadvantages of this technique is
      that extensive cranial exposure is required to align the instruments in the
      proper sagittal trajectory.

PMID- 24945292
TI  - Relative benefit of TLIF versus PSF stratified by diagnostic indication.
AB  - STUDY DESIGN: Case-matched retrospective. OBJECTIVES: The purpose of this study
      is to compare 2-year health-related quality of life (HRQOL) outcomes of patients
      who underwent 1-level or 2-level posterolateral spine fusion (PSF) versus
      transforaminal interbody fusion (TLIF) for degenerative spondylolisthesis, disk
      pathology, and postdecompression instability. SUMMARY OF BACKGROUND DATA: The
      optimal surgical technique for patients with spondylolisthesis or other
      degenerative conditions has not been defined. Historically, PSF was the most
      common procedure, whereas in recent years TLIF has gained popularity. Although
      theoretical advantages for TLIF have been outlined, evidence for improved
      outcomes with the addition of interbody support is limited. METHODS: Patients
      with degenerative spondylolisthesis, with disk pathology and or postdecompression
      instability who underwent 1-level or 2-level TLIF and completed 2 years
      postoperative HRQOL measures were identified from a prospective database. These
      patients were then propensity-matched to a cohort of PSF patients based on age,
      number of surgical levels, body mass index, sex, smoking status, workers'
      compensation status, and preoperative outcome measures including the Oswestry
      Disability Index, SF-36 Physical Component Summary score, SF-36 Mental Composite
      Summary score, and back and leg pain scores. This produced 63 matched pairs with
      degenerative spondylolisthesis, 46 with disk pathology and 32 with
      postdecompression instability. RESULTS: All patients in both groups for each
      cohort reported statistically significant improvement in HRQOL scores at 2 years
      postoperatively compared with baseline. Improvements in the Oswestry Disability
      Index, SF-36 Physical Component Summary score, and back and leg pain scores
      within the spondylolisthesis and disk pathology subgroups were similar between
      patients who had a TLIF compared with those who had a PSF. The postdecompression
      instability subgroup was the only subgroup in which TLIF outperformed PSF for
      every outcome measure. CONCLUSIONS: Clinical outcome was not significantly
      altered with TLIF as compared with PSF in patients with spondylolisthesis or disk
      pathology. However, TLIF resulted in better outcomes at 2 years postoperatively
      in patients with postdecompression instability.

PMID- 24945293
TI  - Comparison and correlation of pelvic parameters between low-grade and high-grade
      spondylolisthesis.
AB  - STUDY DESIGN: This study was retrospectively conducted on 51 patients with L5-S1
      spondylolisthesis. OBJECTIVE: This study was conducted to compare a total of 11
      pelvic parameters, such as the level of displacement by Meyerding method, lumbar
      lordosis, sacral inclination, lumbosacral angle, slip angle, S2 inclination,
      pelvic incidence (PI), L5 inclination, L5 slope, pelvic tilt (PT), and sacral
      slope (SS) between low-grade and high-grade spondylolisthesis, and to investigate
      a correlation of the level of displacement by Meyerding method with other pelvic
      parameters. METHODS: Pelvic parameters were measured using preoperational erect
      lateral spinal simple radiographs. The patients were divided into 39 patients
      with low-grade spondylolisthesis and 12 patients with high-grade
      spondylolisthesis before analysis. In all patients of both groups, 11
      radiographic measurements including the level of displacement by Meyerding
      method, lumbar lordosis, sacral inclination, lumbosacral angle, slip angle, S2
      inclination, PI, L5 inclination, L5 slope, PT, and SS were performed. T test and
      Pearson correlation analysis were conducted to compare and analyze each
      measurement. RESULTS: As for the comparison between the 2 groups, a statistically
      great significance in the level of displacement by Meyerding method, lumbosacral
      angle, slip angle, L5 incidence, PI, and L5 slope (P<=0.001) was shown.
      Meanwhile, a statistical significance in the sacral inclination and PT (P<0.05)
      was also shown. However, no statistical significance in the S2 incidence and SS
      was shown. A correlation of the level of displacement by Meyerding method with
      each parameter was analyzed in the both the groups. A high correlation was
      observed in the lumbar lordosis, lumbosacral angle, slip angle, L5 incidence, and
      L5 slope (Pearson correlation coefficient, P=0.01), as well as the sacral
      inclination, PI, and PT (Pearson correlation coefficient, P=0.05). Meanwhile, no
      correlation was shown in the S2 incidence and SS. CONCLUSIONS: A significant
      difference in the lumbosacral angle, slip angle, L5 incidence, PI, L5 slope,
      sacral inclination, and PT was shown between the patients with high-grade
      spondylolisthesis and patients with low-grade spondylolisthesis. Among the
      aforementioned measurements, the PI showed a significant difference between the 2
      groups and also had a significant correlation with the dislocation level in all
      the patients.

PMID- 24945294
TI  - Sagittal rebalancing of the pelvis and the thoracic spine after pedicle
      subtraction osteotomy at the lumbar level.
AB  - DESIGN: Retrospective study of radiologic records of patients who underwent
      lumbar pedicle subtraction osteotomy (PSO) procedures. OBJECTIVE: To evaluate the
      restoration of spinal balance above and below the osteotomy site after PSO for
      various causes. SUMMARY OF BACKGROUND DATA: The normal sagittal balance of the
      spine has been widely documented. Sagittal imbalance can be surgically treated
      with vertebral osteotomy. Reports have described its technical aspects and local
      radiologic results. Less is known about the spontaneous rebalancing of the spine
      cranially and caudally to the osteotomy site. METHODS: The French Scoliosis Study
      Group conducted a multicenter retrospective study from the records of a combined
      cohort of 356 patients. Spinal balance after PSO was assessed radiologically. In
      this study, we focused specifically on measuring the reorientation of the pelvis
      and upper thoracic segments and investigated the influence of pelvic incidence,
      osteotomy level, and regional lordosis gain. The population was classified
      according to the indication for the procedure: posttraumatic deformity,
      degenerative kyphosis, scoliosis, or ankylosing spondylarthritis. RESULTS: The
      average regional lordosis gain was 26.1 degrees. In the degenerative kyphosis and
      scoliosis groups, the level of osteotomy and the incidence angle tended to
      influence pelvic adaptation (better balance of the caudal portion was associated
      with low-level PSO and low-incidence angle). The posttraumatic deformity cases
      had a specific pattern: balance changes after PSO were limited to the local
      lordosis gain, with less pelvic and thoracic reorientation, probably due to
      spinal flexibility. On the contrary, the spondylarthritis cases showed less
      pelvic and more thoracic reorientation, probably due to hip and spinal stiffness.
      CONCLUSIONS: Better knowledge from a large series of the overall spontaneous
      spinal balance after PSO and the pelvic/thoracic reorientation would be useful
      for preoperative planning of lumbar osteotomies and predicting pelvic and hip
      reorientation. LEVEL OF EVIDENCE: Level II.

PMID- 24945295
TI  - Surgical treatment of scoliosis in osteogenesis imperfecta with cement-augmented
      pedicle screw instrumentation.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To report the early postoperative
      results of scoliosis surgery in osteogenesis imperfecta (OI) patients utilizing
      all pedicle screw constructs and present a novel cementing technique to increase
      pedicle screw purchase in the osteoporotic OI spine. SUMMARY OF BACKGROUND DATA:
      Scoliosis surgery utilizing hooks and wire systems have high complication rates
      in OI. Pedicle screw fixation systems have the biomechanical advantage of 3
      column fixation, and cement augmentation of pedicle screws provides additional
      pull-out strength in the osteoporotic OI spine. METHODS: The clinical and
      radiologic results of 10 consecutive OI patients treated with all pedicle screw
      instrumentation and fusion were retrospectively reviewed. The radiologic data
      included preoperative and postoperative major curve measurements: major curve
      Cobb angle, global coronal balance (GCB), apical vertebral translation (AVT), and
      the lowest instrumented vertebral (LIV) tilt. Operative findings included blood
      loss, surgery time, and additional procedures. All patients received intravenous
      pamidronate therapy preoperatively to increase bone mineral density. RESULTS: Ten
      patients with OI were operated on between 2005 and 2009. Seven had cement
      augmented pedicle screw insertion at the proximal and distal foundations. The
      mean hospital stay was 10+/-7.5 days (range, 4-27 d) and the average follow-up
      period was 25.7+/-13.1 months (range, 14-50 mo). Mean preoperative and
      postoperative major Cobb angles were 83.7+/-23.8 and 40.3+/-14.6 degrees,
      respectively (48% correction; P<0.05). Mean preoperative and postoperative GCB
      deviations were 26.7+/-18.6 and 14.1+/-13.3 mm, respectively (P=0.097). Mean
      preoperative and postoperative AVTs were 69.3+/-29.1 and 29+/-12.2 mm,
      respectively (P<0.05). Preoperative and postoperative LIV tilts were 18.5+/-8.9
      and 5.2+/-3.9 degrees, respectively (P<0.05). At the latest follow-up, the mean
      major curve Cobb angle was 37.7+/-13.1 degrees, the GCB deviation was 13.8+/-5.1
      mm, the AVT was 31.7+/-13.3 mm, and the LIV tilt was 11.3+/-8.8 degrees. There
      was no difference between the early postoperative and the latest follow-up major
      curve Cobb angle, GCB deviation, AVT, or LIV tilt, indicating maintenance of
      correction. The mean blood loss was 23,75 mL (range, 800-45,00 mL). The mean
      operative time was 375.4 minutes (range, 262-491 min). The mean postoperative
      Scoliosis Research Society-22 patient-based outcome scores were 4.6+/-0.7 (out of
      5). There were no instrumentation failures or permanent neurological deficits in
      this series. CONCLUSIONS: Pedicle screw instrumentation in OI scoliosis is safe
      and effective. Cement augmentation in these patients may help to increase the
      pedicle pull-out strength and decrease the screw failure rates, especially at the
      proximal and the distal ends of instrumentation.

PMID- 24945296
TI  - Radiologic evaluation after posterior instrumented surgery for thoracic
      ossification of the posterior longitudinal ligament: union between rostral and
      caudal ossifications.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To investigate, using
      multislice CT images, how thoracic ossification of the posterior longitudinal
      ligament (OPLL) changes with time after thoracic posterior fusion surgery.
      SUMMARY OF BACKGROUND DATA: Few studies have evaluated thoracic OPLL
      preoperatively and post using computed tomography (CT). METHODS: The subjects
      included 19 patients (7 men and 12 women) with an average age at surgery of 52
      years (38-66 y) who underwent indirect posterior decompression with corrective
      fusion and instrumentation at our institute. Minimum follow-up period was 1 year,
      and averaged 3 years 10 months (12-120 mo). Using CT images, we investigated
      fusion range, preoperative and postoperative Cobb angles of thoracic fusion
      levels, intraoperative and postoperative blood loss, operative time, hyperintense
      areas on preoperative MRI of thoracic spine and thickness of the OPLL on the
      reconstructed sagittal, multislice CT images taken before the operation and at 3
      months, 6 months and 1 year after surgery. The basic fusion area was 3 vertebrae
      above and below the OPLL lesion. RESULTS: The mean operative time was 7 hours and
      48 min (4 h 39 min-10 h 28 min), and blood loss was 1631 mL (160-11,731 mL).
      Intramedullary signal intensity change on magnetic resonance images was observed
      at the most severe ossification area in 18 patients. Interestingly, the rostral
      and caudal ossification regions of the OPLLs, as seen on sagittal CT images, were
      discontinuous across the disk space in all patients. Postoperatively, the
      discontinuous segments connected in all patients without progression of OPLL
      thickness by 5.1 months on average. CONCLUSIONS: All patients needing surgery had
      discontinuity across the disk space between the rostral and caudal ossified
      lesions as seen on CT. This discontinuity was considered to be the main reason
      for the myelopathy because a high-intensity area on magnetic resonance imaging
      was seen in 18 of 19 patients at the same level. Rigid fixation with
      instrumentation may allow the discontinuous segments to connect in patients
      without a concomitant thickening of the OPLL.

PMID- 24945297
TI  - Intravertebral polymethylmethacrylate augmentation of anterior cervical
      discectomy fusion and plating in the setting of osteoporosis.
AB  - STUDY DESIGN: Case report and review of the literature. OBJECTIVE: The aim of
      this study was to describe a novel approach for anterior cervical fixation, which
      uses cement augmentation in a patient with osteoporosis. SUMMARY OF BACKGROUND
      DATA: Osteoporotic bone presents a challenge for the treating spine surgeon, and
      techniques to overcome the difficulty of cervical spine fixation in these
      patients are lacking. METHODS: A 75-year-old woman with osteoporosis presented
      with cervical myelopathy and was found to have multiple-level cervical stenosis
      and C3-4 degenerative instability. The patient underwent anterior cervical
      discectomy fusion and plating from C3-7, with vertebroplasty
      polymethylmethacrylate augmentation through the screw pilot holes. Because of the
      patient's grossly soft bone, she also underwent postoperative halo placement.
      RESULTS: No cement extravasation was observed. The halo was removed after 3
      months. At 6 months follow-up, the patient had full resolution of her myelopathy.
      Imaging showed the cervical interbody fusions to be healed at all levels, with no
      screw pullout or graft subsidence. CONCLUSIONS: This represents the first
      comprehensive description of successful cement augmentation during anterior
      cervical discectomy fusion and plating in a patient with osteoporosis,
      accomplishing both an increase in screw pullout strength and a decreased
      likelihood of graft subsidence. With further study, this technique may represent
      a viable treatment option in patients with osteoporosis requiring cervical
      decompression and fusion.

PMID- 24945298
TI  - Analysis of sagittal balance of ankylosing spondylitis using spinopelvic
      parameters.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To analyze sagittal spinopelvic
      parameters in ankylosing spondylitis (AS) patients. SUMMARY OF BACKGROUND DATA:
      There are little data on the relationship between the sagittal spinopelvic
      parameters and AS. METHODS: The study and control groups comprised 90 AS patients
      and 40 controls. Participants were classified into 3 groups: normal (n=40),
      sagittal balance (n=58), and sagittal imbalance (n=32) groups. All underwent
      lateral radiograph of the whole spine including hip joints. The radiographic
      parameters were sacral slope, pelvic tilting, pelvic incidence, overhang of S1,
      thoracic kyphosis, lumbar lordosis, and C7 plumbline. Statistical analysis was
      performed to identify significant differences between the 2 groups. Correlations
      between radiological parameters and symptoms were sought. RESULTS: AS patients
      and controls were found to be significantly different in terms of sagittal
      balance, sacral slope, pelvic tilt, pelvic incidence, S1 overhang, and lumbar
      lordosis. However, no significant difference was observed between these 2 groups
      for thoracic kyphosis (P>0.05). Of the 90 AS patients, 32 patients (5 women and
      27 men) were assigned to the sagittal imbalance group and 58 (12 women and 46
      men) to the sagittal balance group. There was a significant difference in all
      sagittal parameters and visual analogue scale (VAS) score between these 2 groups.
      Correlation analysis revealed significant relationships between sagittal
      parameters in AS. However, there was no association between sacral slope and S1
      overhang, and between pelvic incidence and VAS score. Stepwise logistic
      regression analysis revealed that pelvic tilt contributed significantly to
      sagittal balance. CONCLUSIONS: AS patients and normal controls were found to be
      significantly different in terms of sagittal spinopelvic parameters. Significant
      relationships were found between sagittal spinopelvic parameters in AS patients.
      Pelvic tilt was a significant parameter in determination of sagittal balance in
      AS patient. Furthermore, VAS scores were significantly related to sagittal spinal
      parameters which were closely related with pelvic orientation in AS patients.

PMID- 24945299
TI  - Analysis of cervical pedicle with reconstructed computed tomography imaging in
      Korean population: feasibility and surgical anatomy.
AB  - STUDY DESIGN: We analyzed the anatomy of C3-C6 cervical pedicles with
      reconstructed computed tomography images. OBJECTIVES: The objective of the study
      was to estimate the feasibility and to understand the surgical anatomy in order
      to reduce pedicle penetration. SUMMARY OF BACKGROUND DATA: It is necessary to
      minimize pedicle penetration by anatomic analysis of cervical pedicles. Many
      studies have been conducted on cervical pedicle anatomy and cervical pedicle
      screw fixation, yet there are debates about the feasibility and surgical anatomy.
      METHODS: Oblique axial and oblique sagittal images were reconstructed from a 1 mm
      cut computed tomography image. The pedicle transverse diameter, pedicle length,
      pedicle convergence angle (CA), and pedicle distance were measured on the oblique
      axial images. The pedicle sagittal diameter, pedicle sagittal angle (SA), and
      lateral mass index were measured on the oblique sagittal images. The multiple t
      test was used for statistical analysis. RESULTS: The averages of the pedicle
      transverse diameter ranged from 5.79 to 6.19 mm, the pedicle length ranged from
      16.24 to 17.56 mm, the CA ranged from 47.49 to 48.86 degrees, the pedicle
      distance ranged from 22.67 to 24.93 mm, the SA ranged from -15.43 to 19.98
      degrees, and the lateral mass index ranged from 0.64 to 1.25. CONCLUSIONS:
      Because of a tight safe margin, to reduce pedicle penetration the screw should be
      inserted along the pedicle. With regard to SA, C3 and C4 have a risk of upper end
      plate penetration. However, C5 and C6 have a risk of facet joint violation, which
      needs C4 and C5 inferior articular process removal for screw placement. The entry
      point at C3 and C4 is near one third of the lateral mass height from the
      posterior border of the superior articular process at the posterolateral border
      of the lateral mass. The entry point at C5 is near the posterolateral border of
      the superior articular process and that at C6 is superior to the posterior border
      of the superior articular process at a line medial to the posterolateral border
      of the C5 lateral mass. During insertion, not only CA but even SA should be
      considered carefully to reduce pedicle penetration.

PMID- 24945300
TI  - Methy-Pipe: an integrated bioinformatics pipeline for whole genome bisulfite
      sequencing data analysis.
AB  - DNA methylation, one of the most important epigenetic modifications, plays a
      crucial role in various biological processes. The level of DNA methylation can be
      measured using whole-genome bisulfite sequencing at single base resolution.
      However, until now, there is a paucity of publicly available software for
      carrying out integrated methylation data analysis. In this study, we implemented
      Methy-Pipe, which not only fulfills the core data analysis requirements (e.g.
      sequence alignment, differential methylation analysis, etc.) but also provides
      useful tools for methylation data annotation and visualization. Specifically, it
      uses Burrow-Wheeler Transform (BWT) algorithm to directly align bisulfite
      sequencing reads to a reference genome and implements a novel sliding window
      based approach with statistical methods for the identification of differentially
      methylated regions (DMRs). The capability of processing data parallelly allows it
      to outperform a number of other bisulfite alignment software packages. To
      demonstrate its utility and performance, we applied it to both real and simulated
      bisulfite sequencing datasets. The results indicate that Methy-Pipe can
      accurately estimate methylation densities, identify DMRs and provide a variety of
      utility programs for downstream methylation data analysis. In summary, Methy-Pipe
      is a useful pipeline that can process whole genome bisulfite sequencing data in
      an efficient, accurate, and user-friendly manner. Software and test dataset are
      available at http://sunlab.lihs.cuhk.edu.hk/methy-pipe/. 

PMID- 24945301
TI  - An evaluation of dose equivalence between synchrotron microbeam radiation therapy
      and conventional broad beam radiation using clonogenic and cell impedance assays.
AB  - BACKGROUND: High-dose synchrotron microbeam radiation therapy (MRT) has shown the
      potential to deliver improved outcomes over conventional broadbeam (BB) radiation
      therapy. To implement synchrotron MRT clinically for cancer treatment, it is
      necessary to undertake dose equivalence studies to identify MRT doses that give
      similar outcomes to BB treatments. AIM: To develop an in vitro approach to
      determine biological dose equivalence between MRT and BB using two different cell
      based assays. METHODS: The acute response of tumour and normal cell lines
      (EMT6.5, 4T1.2, NMuMG, EMT6.5ch, 4T1ch5, SaOS-2) to MRT (50-560 Gy) and BB (1.5
      10 Gy) irradiation was investigated using clonogenic and real time cell impedance
      sensing (RT-CIS)/xCELLigence assays. MRT was performed using a lattice of 25 or
      50 um-wide planar, polychromatic kilovoltage X-ray microbeams with 200 um peak
      separation. BB irradiations were performed using a Co60 teletherapy unit or a
      synchrotron radiation source. BB doses that would generate biological responses
      similar to MRT were calculated by data interpolation and verified by clonogenic
      and RT-CIS assays. RESULTS: For a given cell line, MRT equivalent BB doses
      identified by RT-CIS/xCELLigence were similar to those identified by clonogenic
      assays. Dose equivalence between MRT and BB were verified in vitro in two cell
      lines; EMT6.5ch and SaOS-2 by clonogenic assays and RT-CIS/xCELLigence. We found
      for example, that BB doses of 3.4+/-0.1 Gy and 4.40+/-0.04 Gy were
      radiobiologically equivalent to a peak, microbeam dose of 112 Gy using clonogenic
      and RT-CIS assays respectively on EMT6.5ch cells. CONCLUSION: Our data provides
      the first determination of biological dose equivalence between BB and MRT
      modalities for different cell lines and identifies RT-CIS/xCELLigence assays as a
      suitable substitute for clonogenic assays. These results will be useful for the
      safe selection of MRT doses for future veterinary and clinical trials.

PMID- 24945302
TI  - Mitogen and stress activated kinases act co-operatively with CREB during the
      induction of human cytomegalovirus immediate-early gene expression from latency.
AB  - The devastating clinical consequences associated with human cytomegalovirus
      (HCMV) infection and reactivation underscores the importance of understanding
      triggers of HCMV reactivation in dendritic cells (DC). Here we show that ERK
      mediated reactivation is dependent on the mitogen and stress activated kinase
      (MSK) family. Furthermore, this MSK mediated response is dependent on CREB
      binding to the viral major immediate early promoter (MIEP). Specifically, CREB
      binding to the MIEP provides the target for MSK recruitment. Importantly, MSK
      mediated phosphorylation of histone H3 is required to promote histone de
      methylation and the subsequent exit of HCMV from latency. Taken together, these
      data suggest that CREB binding to the MIEP is necessary for the recruitment of
      the kinase activity of MSKs to initiate the chromatin remodelling at the MIEP
      required for reactivation. Thus the importance of CREB during HCMV reactivation
      is to promote chromatin modifications conducive for viral gene expression as well
      as acting as a classical transcription factor. Clearly, specific inhibition of
      this interaction between CREB and MSKs could provide a strategy for therapeutic
      intervention. 

PMID- 24945303
TI  - Deficiency of p110delta isoform of the phosphoinositide 3 kinase leads to
      enhanced resistance to Leishmania donovani.
AB  - BACKGROUND: Visceral leishmaniasis is the most clinically relevant and dangerous
      form of human leishmaniasis. Most traditional drugs for treatment of
      leishmaniasis are toxic, possess many adverse reactions and drug resistance is
      emerging. Therefore, there is urgent need for identification of new therapeutic
      targets. Recently, we found that mice with an inactivating knock-in mutation in
      the p110delta isoform of pi3k, (p110delta(d910a)) are hyper resistant to L.
      major, develop minimal cutaneous lesion and rapidly clear their parasite. Here,
      we investigated whether pi3k signaling also regulates resistance to L. donovani,
      one of the causative agents of visceral leishmaniasis. METHODOLOGY/PRINCIPAL
      FINDINGS: WT and p110delta(D910A) mice (on a BALB/c background) were infected
      with L. donovani. At different time points, parasite burden and granuloma
      formation were assessed. T and B cell responses in the liver and spleen were
      determined. In addition, Tregs were expanded in vivo and its impact on resistance
      was assessed. We found that p110delta(D910A) mice had significantly reduced
      splenomegaly and hepatomegaly and these organs harbored significantly fewer
      parasites than those of WT mice. Interestingly, infected p110delta(D910A) mice
      liver contains fewer and less organized granulomas than their infected WT
      counterparts. Cells from p110delta(D910A) mice were significantly impaired in
      their ability to produce cytokines compared to WT mice. The percentage and
      absolute numbers of Tregs in infected p110delta(D910A) mice were lower than those
      in WT mice throughout the course of infection. In vivo expansion of Tregs in
      infected p110delta(D910A) mice abolished their enhanced resistance to L. donovani
      infection. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the enhanced
      resistance of p110delta(D910A) mice to L. donovani infection is due to impaired
      activities of Tregs. They further show that resistance to Leishmania in the
      absence of p110delta signaling is independent of parasite species, suggesting
      that targeting the PI3K signaling pathway may be useful for treatment of both
      visceral and cutaneous leishmaniasis.

PMID- 24945304
TI  - Differential activation of acid sphingomyelinase and ceramide release determines
      invasiveness of Neisseria meningitidis into brain endothelial cells.
AB  - The interaction with brain endothelial cells is central to the pathogenicity of
      Neisseria meningitidis infections. Here, we show that N. meningitidis causes
      transient activation of acid sphingomyelinase (ASM) followed by ceramide release
      in brain endothelial cells. In response to N. meningitidis infection, ASM and
      ceramide are displayed at the outer leaflet of the cell membrane and condense
      into large membrane platforms which also concentrate the ErbB2 receptor. The
      outer membrane protein Opc and phosphatidylcholine-specific phospholipase C that
      is activated upon binding of the pathogen to heparan sulfate proteoglycans, are
      required for N. meningitidis-mediated ASM activation. Pharmacologic or genetic
      ablation of ASM abrogated meningococcal internalization without affecting
      bacterial adherence. In accordance, the restricted invasiveness of a defined set
      of pathogenic isolates of the ST-11/ST-8 clonal complex into brain endothelial
      cells directly correlated with their restricted ability to induce ASM and
      ceramide release. In conclusion, ASM activation and ceramide release are
      essential for internalization of Opc-expressing meningococci into brain
      endothelial cells, and this segregates with invasiveness of N. meningitidis
      strains. 

PMID- 24945305
TI  - Q-ball of inferior fronto-occipital fasciculus and beyond.
AB  - The inferior fronto-occipital fasciculus (IFOF) is historically described as the
      longest associative bundle in the human brain and it connects various parts of
      the occipital cortex, temporo-basal area and the superior parietal lobule to the
      frontal lobe through the external/extreme capsule complex. The exact functional
      role and the detailed anatomical definition of the IFOF are still under debate
      within the scientific community. In this study we present a fiber tracking
      dissection of the right and left IFOF by using a q-ball residual-bootstrap
      reconstruction of High-Angular Resolution Diffusion Imaging (HARDI) data sets in
      20 healthy subjects. By defining a single seed region of interest on the coronal
      fractional anisotropy (FA) color map of each subject, we investigated all the
      pathways connecting the parietal, occipital and posterior temporal cortices to
      the frontal lobe through the external/extreme capsule. In line with recent post
      mortem dissection studies we found more extended anterior-posterior association
      connections than the "classical" fronto-occipital representation of the IFOF. In
      particular the pathways we evidenced showed: a) diffuse projections in the
      frontal lobe, b) fronto-parietal lobes connections trough the external capsule in
      almost all the subjects and c) widespread connections in the posterior regions.
      Our study represents the first consistent in vivo demonstration across a large
      group of individuals of these novel anterior and posterior terminations of the
      IFOF detailed described only by post-mortem anatomical dissection. Furthermore
      our work establishes the feasibility of consistent in vivo mapping of this
      architecture with independent in vivo methodologies. In conclusion q-ball
      tractography dissection supports a more complex definition of IFOF, which
      includes several subcomponents likely underlying specific function. 

PMID- 24945307
TI  - Depletion of florfenicol and florfenicol amine residues in chicken eggs.
AB  - 1. The aim of this study was to develop a suitable method for the analysis of
      florfenicol (FF) and its metabolite florfenicol amine (FFA) in chicken eggs and
      to determine FF and FFA residue depletion in eggs of laying hens. 2. The analytes
      were extracted from yolk, albumen and whole egg by phosphate buffer and ethyl
      acetate. Following purification, samples were analysed by high-performance liquid
      chromatography. 3. Fifty laying hens were divided into 5 groups, and each hen
      received doses of 20 mg/kg FF: Group 1 (received a single oral dose by gavage);
      Group 2 (a single intramuscular dose); Group 3 (a single subcutaneous dose);
      Group 4 (multiple oral doses for 3 d) and Group 5 (multiple oral doses for 5 d).
      4. Limits of detection and of quantitation values were 1.94 and 6.45 g/10(9) g
      (ppb) for FF, respectively, and 0.48 and 1.58 ppb for FFA, respectively. Relative
      standard deviation values of intra-day and inter-day variation below 11% also
      confirmed the usefulness of the method for analysing FF and FFA in eggs. 5. From
      the first day of both oral and parenteral administration, FF and FFA were
      detected at 0.1% and 0.08% of dosage, respectively, and 57% of the drugs were
      eliminated from the egg yolk. Elimination time of FF was 8 d in Groups 1, 2 and
      3; 9 d in Group 4 and 10 d in Group 5.

PMID- 24945306
TI  - Telemedicine diagnosis of cytomegalovirus retinitis by nonophthalmologists.
AB  - IMPORTANCE: Cytomegalovirus (CMV) retinitis continues to be a leading cause of
      blindness in many developing countries. Telemedicine holds the potential to
      increase the number of people screened for CMV retinitis, but it is unclear
      whether nonophthalmologists could be responsible for interpreting fundus
      photographs captured in a telemedicine program. OBJECTIVE: To determine the
      accuracy of nonophthalmologist photographic graders in diagnosing CMV retinitis
      from digital fundus photographs. DESIGN, SETTING, AND PARTICIPANTS: Fifteen
      nonexpert graders each evaluated 182 mosaic retinal images taken from the eyes of
      patients with AIDS who were evaluated at the Ocular Infectious Diseases Clinic at
      Chiang Mai University in Chiang Mai, Thailand. MAIN OUTCOMES AND MEASURES:
      Graders diagnosed each image as CMV retinitis present, CMV retinitis absent, or
      unknown. The results from each grader were compared with those of an indirect
      ophthalmoscopic examination from an experienced on-site ophthalmologist as well
      as with the consensus grade given by a panel of CMV retinitis experts. RESULTS:
      Relative to the on-site ophthalmologist, the sensitivity of remote CMV retinitis
      diagnosis by nonexpert graders ranged from 64.0% to 95.5% (mean, 84.1%; 95% CI,
      78.6%-89.6%)), and the specificity ranged from 65.6% to 92.5% (mean, 82.3%; 95%
      CI, 76.6%-88.0%)). Agreement between nonexpert and expert graders was high: the
      mean sensitivity and specificity values of nonexpert diagnosis using expert
      consensus as the reference standard were 93.2% (95% CI, 90.6%-95.8%) and 88.4%
      (95% CI, 85.4%-91.1%), respectively. Mean intrarater reliability also was high
      (mean Cohen kappa, 0.83; 95% CI, 0.78-0.87). CONCLUSIONS AND RELEVANCE: The
      sensitivity and specificity of remote diagnosis of CMV retinitis by nonexpert
      graders was variable, although several nonexperts achieved a level of accuracy
      comparable to that of CMV retinitis experts. More intensive training and periodic
      evaluations would be required if nonexperts are to be used in clinical practice.

PMID- 24945308
TI  - Physical exercise promotes recovery of neurological function after ischemic
      stroke in rats.
AB  - Although physical exercise is an effective strategy for treatment of ischemic
      stroke, the underlying protective mechanisms are still not well understood. It
      has been recently demonstrated that neural progenitor cells play a vital role in
      the recovery of neurological function (NF) through differentiation into mature
      neurons. In the current study, we observed that physical exercise significantly
      reduced the infarct size and improved damaged neural functional recovery after an
      ischemic stroke. Furthermore, we found that the treatment not only exhibited a
      significant increase in the number of neural progenitor cells and neurons but
      also decreased the apoptotic cells in the peri-infarct region, compared to a
      control in the absence of exercise. Importantly, the insulin-like growth factor-1
      (IGF-1)/Akt signaling pathway was dramatically activated in the peri-infarct
      region of rats after physical exercise training. Therefore, our findings suggest
      that physical exercise directly influences the NF recovery process by increasing
      neural progenitor cell count via activation of the IGF-1/Akt signaling pathway. 

PMID- 24945309
TI  - Correlation between BPI gene upstream CpG island methylation and mRNA expression
      in piglets.
AB  - Diarrhea and edematous disease are two major causes of mortality in postweaning
      piglets, and these conditions lead to huge economic losses in the swine industry.
      E. coli F18 is the primary causative agent of these two diseases.
      Bactericidal/permeability-increasing protein (BPI) plays an important role in the
      natural defense of the host. The aim of this study was to determine the
      correlation between BPI gene upstream CpG island methylation and mRNA expression.
      In this study, bisulfite sequencing PCR (BSP) was used to detect the methylation
      status of the BPI gene upstream CpG island and fluorescence quantitative PCR was
      used to detect BPI expression in the duodenum of piglets from birth to weaning
      age. BPI upstream CpG islands were shown to have many putative transcription
      factor binding sites, 10 CpG sites and every CpG site was methylated. The CpG
      island methylation level was lowest in 30-day piglets and was significantly lower
      than levels in 8-day piglets (p<0.05). BPI mRNA expression was significantly
      higher in 30-day piglets than at any other age (p<0.05). Pearson's correlation
      analysis showed that the methylation status of the CpG island was negatively
      correlated with BPI mRNA expression. Statistical significances were found in
      CpG_1, CpG_3, CpG_4, CpG_7 and CpG_10 (p<0.05). The data indicate that BPI
      expression is improved by demethylation of the BPI gene upstream CpG island.
      Furthermore, CpG_1, CpG_3, CpG_4, CpG_7 and CpG_10 may be critical sites in the
      regulation of BPI gene expression.

PMID- 24945310
TI  - The effects of CoCl2 on HIF-1alpha protein under experimental conditions of
      autoprogressive hypoxia using mouse models.
AB  - It is well known that cobalt chloride (CoCl2) can enhance the stability of
      hypoxia-inducible factor (HIF)-1alpha. The aim of this study is to detect the
      effect of CoCl2 on the hypoxia tolerance of mice which were repeatedly exposed to
      autoprogressive hypoxia. Balb/c mice were randomly divided into groups of
      chemical pretreatment and normal saline (NS), respectively injected with CoCl2
      and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs
      (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular
      recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal
      slices and real-time were used in this study. Our results demonstrated that the
      tolerance of mice to hypoxia, the changes of HIF-1alpha protein level and HIF-1
      DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO)
      and vascular endothelial growth factor (VEGF), and the disappearance time of
      population spikes of hippocampal slices were substantially different between the
      control group and the CoCl2 group. Over-induction of HIF-1alpha by pretreatment
      with CoCl2 before hypoxia did not increase the hypoxia tolerance. 

PMID- 24945311
TI  - Celecoxib suppresses the phosphorylation of STAT3 protein and can enhance the
      radiosensitivity of medulloblastoma-derived cancer stem-like cells.
AB  - Medulloblastoma (MB) is a malignant primary brain tumor with poor prognosis. MB
      derived CD133/Nestin double-positive cells (MB-DPs) exhibit cancer stem-like cell
      (CSC)-like properties that may contribute to chemoradioresistance, tumorigenesis
      and recurrence. In various tumors, signal transducer and activator of
      transcription 3 (STAT3) upregulation including MB which can regulate the
      expression of Nestin. Celecoxib, a selective COX-2 inhibitor, has been shown to
      potentially reduce STAT3 phosphorylation. The aim of the present study was to
      investigate the role of celecoxib in enhancing the effects of ionizing
      radiotherapy (IR) on MB-DP. MB-DPs and MB-derived CD133/Nestin double-negative
      cells (MB-DNs) were isolated from medulloblastoma cell line Daoy. Then, both of
      them were treated with celecoxib in different concentrations, and cell viability
      was assessed. The assays of cell survival, sphere formation, radiosensitivity,
      colony formation, apoptotic activity and mouse xenografting experiments in MB-DPs
      and MB-DNs treated with celecoxib alone, radiation alone, or celecoxib combined
      with radiation were further evaluated. We isolated MB-DPs from MB cell line Daoy,
      which exhibited typical CSC-like characteristics. Microarray analysis and Western
      blotting both indicated the upregulation of Janus kinase (JAK)-STAT cascade and
      STAT3 phosphorylation. Incubation with celecoxib dose-dependently suppressed the
      CSC-like properties and enhanced the IR effect on the induction of apoptosis, as
      detected by TUNEL assay and staining for Caspase 3 and Annexin V. Finally,
      celecoxib also enhanced the IR effect to suppress tumorigenesis and
      synergistically improve the recipient survival in orthotopic MB-derived
      CD133/Nestin double-positive cells (MB-DP cells) bearing mice. 

PMID- 24945313
TI  - Cellulose nanocrystals/ZnO as a bifunctional reinforcing nanocomposite for
      poly(vinyl alcohol)/chitosan blend films: fabrication, characterization and
      properties.
AB  - In this study, cellulose nanocrystals/zinc oxide (CNCs/ZnO) nanocomposites were
      dispersed as bifunctional nano-sized fillers into poly(vinyl alcohol) (PVA) and
      chitosan (Cs) blend by a solvent casting method to prepare PVA/Cs/CNCs/ZnO bio
      nanocomposites films. The morphology, thermal, mechanical and UV-vis absorption
      properties, as well antimicrobial effects of the bio-nanocomposite films were
      investigated. It demonstrated that CNCs/ZnO were compatible with PVA/Cs and
      dispersed homogeneously in the polymer blend matrix. CNCs/ZnO improved tensile
      strength and modulus of PVA/Cs significantly. Tensile strength and modulus of bio
      nanocomposite films increased from 55.0 to 153.2 MPa and from 395 to 932 MPa,
      respectively with increasing nano-sized filler amount from 0 to 5.0 wt %. The
      thermal stability of PVA/Cs was also enhanced at 1.0 wt % CNCs/ZnO loading. UV
      light can be efficiently absorbed by incorporating ZnO nanoparticles into a
      PVA/Cs matrix, signifying that these bio-nanocomposite films show good UV
      shielding effects. Moreover, the biocomposites films showed antibacterial
      activity toward the bacterial species Salmonella choleraesuis and Staphylococcus
      aureus. The improved physical properties obtained by incorporating CNCs/ZnO can
      be useful in variety uses. 

PMID- 24945314
TI  - First-principles study of siloxene and germoxene: stable conformations,
      electronic properties, and defects.
AB  - Interest in two-dimensional (2D) forms of Si and Ge has surged recently, with a
      focus on silicene and germanene, the Si- and Ge-based analogues of graphene, as
      well as their derivatives. Siloxene and germoxene are 2D materials made of
      honeycomb Si and Ge backbone sheets that are decorated with H atoms and OH
      groups. Here we use first-principles calculations to probe the properties of
      their various conformations. We show that the most stable siloxene (and
      germoxene) polymorph is the so-called washboard structure, and not the chair
      geometry assumed in previous studies. The stability of the washboard
      configuration relates to the formation of a network of hydrogen bonds between its
      hydroxyl groups. We also find with hybrid functional calculations that siloxene
      and germoxene are wide band-gap semiconductors with gap values of 3.20 eV and
      2.64 eV, respectively. Finally, we show that H and OH vacancies introduce spin
      polarization in these 2D materials and have a tendency to pair up in stable di
      vacancies.

PMID- 24945312
TI  - Contribution of chitinase A's C-terminal vacuolar sorting determinant to the
      study of soluble protein compartmentation.
AB  - Plant chitinases have been studied for their importance in the defense of crop
      plants from pathogen attacks and for their peculiar vacuolar sorting
      determinants. A peculiarity of the sequence of many family 19 chitinases is the
      presence of a C-terminal extension that seems to be important for their correct
      recognition by the vacuole sorting machinery. The 7 amino acids long C-terminal
      vacuolar sorting determinant (CtVSD) of tobacco chitinase A is necessary and
      sufficient for the transport to the vacuole. This VSD shares no homology with
      other CtVSDs such as the phaseolin's tetrapeptide AFVY (AlaPheValTyr) and it is
      also sorted by different mechanisms. While a receptor for this signal has not yet
      been convincingly identified, the research using the chitinase CtVSD has been
      very informative, leading to the observation of phenomena otherwise difficult to
      observe such as the presence of separate vacuoles in differentiating cells and
      the existence of a Golgi-independent route to the vacuole. Thanks to these new
      insights in the endoplasmic reticulum (ER)-to-vacuole transport, GFPChi (Green
      Fluorescent Protein carrying the chitinase A CtVSD) and other markers based on
      chitinase signals will continue to help the investigation of vacuolar biogenesis
      in plants. 

PMID- 24945315
TI  - A new flavonol glycoside from the medicinal halophyte Suaeda fruticosa.
AB  - A new flavonol glycoside, namely 3-(alpha-rhamnopyranosyl-(1 -> 2)-[beta
      xylopyranosyl-(1 -> 6)]-beta-glucopyranosyloxy) isorhamnetin was reported from
      methanol extracts of aerial parts of Suaeda fruticosa for the first time. In this
      work, liquid chromatography coupled to atmospheric pressure chemical ionisation
      mass spectrometry, high-resolution mass spectrometry and nuclear magnetic
      resonance spectroscopy were used to identify this new compound. Structure was
      elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC
      and (1)H-(1)H COSY. Antioxidant potentialities of a pure compound were evaluated.
      The estimation of antioxidant capacities using oxygen radical absorbance capacity
      (ORAC method) and a cell based-assay (WS1) indicated that this new flavonol
      exhibited the highest antioxidant activities with an ORAC value of 5.0 +/- 0.3
      MUmol Trolox/MUmol and inhibited the tBH-induced oxidation of 2',7'
      dichlorofluorescin with an IC50 value of 4.9 +/- 0.6 MUM.

PMID- 24945316
TI  - Hydrogen-saturated saline protects intensive narrow band noise-induced hearing
      loss in guinea pigs through an antioxidant effect.
AB  - The purpose of the current study was to evaluate hydrogen-saturated saline
      protecting intensive narrow band noise-induced hearing loss. Guinea pigs were
      divided into three groups: hydrogen-saturated saline; normal saline; and control.
      For saline administration, the guinea pigs were given daily abdominal injections
      (1 ml/100 g) 3 days before and 1 h before narrow band noise exposure (2.5-3.5 kHz
      130 dB SPL, 1 h). The guinea pigs in the control group received no treatment. The
      hearing function was assessed by the auditory brainstem response (ABR) and
      distortion product otoacoustic emission (DPOAE) recording. The changes of free
      radicals in the cochlea before noise exposure, and immediately and 7 days after
      noise exposure were also examined. By Scanning electron microscopy and succinate
      dehydrogenase staining, we found that pre-treatment with hydrogen-saturated
      saline significantly reduced noise-induced hair cell damage and hearing loss. We
      also found that the malondialdehyde, lipid peroxidation, and hydroxyl levels were
      significantly lower in the hydrogen-saturated saline group after noise trauma,
      indicating that hydrogen-saturated saline can decrease the amount of harmful free
      radicals caused by noise trauma. Our findings suggest that hydrogen-saturated
      saline is effective in preventing intensive narrow band noise-induced hearing
      loss through the antioxidant effect. 

PMID- 24945317
TI  - The relationship of season of birth with refractive error in very young children
      in eastern China.
AB  - PURPOSE: To determine the association of season of birth and refractive error in
      very young Chinese children in China. METHODS: We conducted a population-based
      study of Chinese children aged 0 to 3 years residing in eastern China. Refraction
      was determined by non-cyclopegic autorefraction using a hand-held autorefractor.
      Date of birth was retrieved from birth certificate of the individual subjects. A
      generalized linear regression model was fitted to estimate the regression
      coefficient and 95% confidence interval (CI) of refractive error for season of
      birth, adjusting for confounders. RESULTS: Of the 1385 children eligible to
      participate, 1222 (88.2%) were examined. Refractive error data were available for
      1219 children. The mean spherical equivalent were 1.21 diopters (D) in children
      born Spring, 1.24 D in those born in Summer, 1.23 D in those born in Autumn, 1.15
      D in Winter. After adjusting for age, sex, father's educational level, birth
      weight and the number of summers between birth and examination date the children
      have been exposed to, children born in winter had a 0.12 D more myopic refraction
      compared with those born in summer (regression coefficient: -0.12; 95% CI, -0.27,
      0.06; P = 0.006). The association between season of birth and cylinder power was
      not statistically significant. CONCLUSIONS: In China, children born in winter had
      a more myopic refraction compared with those born in other seasons. The observed
      association between season of birth and refractive error was independent of
      parental educational level and birth weight, suggesting that light level may have
      a small impact on refractive development in early life.

PMID- 24945318
TI  - Antibacterial, antiviral, and antifungal properties of wines and winery
      byproducts in relation to their flavonoid content.
AB  - Grapes produce organic compounds that may be involved in the defense of the
      plants against invading phytopathogens. These metabolites include numerous
      phenolic compounds that are also active against human pathogens. Grapes are used
      to produce a variety of wines, grape juices, and raisins. Grape pomace, seeds,
      and skins, the remains of the grapes that are a byproduct of winemaking, also
      contain numerous bioactive compounds that differ from those found in grapes and
      wines. This overview surveys and interprets our present knowledge of the
      activities of wines and winery byproducts and some of their bioactive components
      against foodborne (Bacillus cereus, Campylobacter jejuni, Escherichia coli,
      Listeria monocytogenes, Salmonella enterica, Staphylococcus aureus, Yersinia
      enterocolitica, Vibrio cholerae, Vibrio vulnificus), medical (Helicobacter
      pylori, Klebsiella pneumoniae), and oral pathogenic bacteria, viruses (adeno,
      cytomegalo, hepatitis, noro, rota), fungi (Candida albicans, Botrytis cinerea),
      parasites (Eimeria tenella, Trichomonas vaginalis), and microbial toxins
      (ochratoxin A, Shiga toxin) in culture, in vivo, and in/on food (beef, chicken,
      frankfurters, hot dogs, lettuce, oysters, peppers, pork, sausages, soup, spinach)
      in relation to composition and sensory properties. Also covered are antimicrobial
      wine marinades, antioxidative and immunostimulating aspects, and adverse effects
      associated with wine consumption. The collated information and suggested research
      needs might facilitate and guide further studies needed to optimize the use of
      wines and byproducts to help improve microbial food safety and prevent or treat
      animal and human infections. 

PMID- 24945320
TI  - A dimerized HMX1 inhibits EPHA6/epha4b in mouse and zebrafish retinas.
AB  - HMX1 is a homeobox-containing transcription factor implicated in eye development
      and responsible for the oculo-auricular syndrome of Schorderet-Munier
      Franceschetti. HMX1 is composed of two exons with three conserved domains in exon
      2, a homeobox and two domains called SD1 and SD2. The function of the latter two
      domains remains unknown. During retinal development, HMX1 is expressed in a
      polarized manner and thus seems to play a role in the establishment of retinal
      polarity although its exact role and mode of action in eye development are
      unknown. Here, we demonstrated that HMX1 dimerized and that the SD1 and
      homeodomains are required for this function. In addition, we showed that proper
      nuclear localization requires the presence of the homeodomain. We also identified
      that EPHA6, a gene implicated in retinal axon guidance, is one of its targets in
      eye development and showed that a dimerized HMX1 is needed to inhibit EPHA6
      expression. 

PMID- 24945319
TI  - CPF-associated phosphatase activity opposes condensin-mediated chromosome
      condensation.
AB  - Functional links connecting gene transcription and condensin-mediated chromosome
      condensation have been established in species ranging from prokaryotes to
      vertebrates. However, the exact nature of these links remains misunderstood. Here
      we show in fission yeast that the 3' end RNA processing factor Swd2.2, a
      component of the Cleavage and Polyadenylation Factor (CPF), is a negative
      regulator of condensin-mediated chromosome condensation. Lack of Swd2.2 does not
      affect the assembly of the CPF but reduces its association with chromatin. This
      causes only limited, context-dependent effects on gene expression and
      transcription termination. However, CPF-associated Swd2.2 is required for the
      association of Protein Phosphatase 1 PP1(Dis2) with chromatin, through an
      interaction with Ppn1, a protein that we identify as the fission yeast homologue
      of vertebrate PNUTS. We demonstrate that Swd2.2, Ppn1 and PP1Dis2 form an
      independent module within the CPF, which provides an essential function in the
      absence of the CPF-associated Ssu72 phosphatase. We show that Ppn1 and Ssu72,
      like Swd2.2, are also negative regulators of condensin-mediated chromosome
      condensation. We conclude that Swd2.2 opposes condensin-mediated chromosome
      condensation by facilitating the function of the two CPF-associated phosphatases
      PP1 and Ssu72.

PMID- 24945323
TI  - Bacillus anthracis-like bacteria and other B. cereus group members in a microbial
      community within the International Space Station: a challenge for rapid and easy
      molecular detection of virulent B. anthracis.
AB  - For some microbial species, such as Bacillus anthracis, the etiologic agent of
      the disease anthrax, correct detection and identification by molecular methods
      can be problematic. The detection of virulent B. anthracis is challenging due to
      multiple virulence markers that need to be present in order for B. anthracis to
      be virulent and its close relationship to Bacillus cereus and other members of
      the B. cereus group. This is especially the case in environments where build-up
      of Bacillus spores can occur and several representatives of the B. cereus group
      may be present, which increases the chance for false-positives. In this study we
      show the presence of B. anthracis-like bacteria and other members of the B.
      cereus group in a microbial community within the human environment of the
      International Space Station and their preliminary identification by using
      conventional culturing as well as molecular techniques including 16S rDNA
      sequencing, PCR and real-time PCR. Our study shows that when monitoring the
      microbial hygiene in a given human environment, health risk assessment is
      troublesome in the case of virulent B. anthracis, especially if this should be
      done with rapid, easy to apply and on-site molecular methods. 

PMID- 24945325
TI  - Dr. Sofia Aliaga Interview.

PMID- 24945324
TI  - The need for more research and public health interventions on dengue Fever in
      Burkina Faso.

PMID- 24945322
TI  - An HIV epidemic model based on viral load dynamics: value in assessing empirical
      trends in HIV virulence and community viral load.
AB  - Trends in HIV virulence have been monitored since the start of the AIDS pandemic,
      as studying HIV virulence informs our understanding of HIV epidemiology and
      pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary
      process, using set point viral load (SPVL) as a proxy, to make inferences about
      empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based
      epidemic model based on HIV viral load dynamics. The model contains functions for
      viral load and transmission, SPVL and disease progression, viral load
      trajectories in multiple stages of infection, and the heritability of SPVL across
      transmissions. We find that HIV virulence evolves to an intermediate level that
      balances infectiousness with longer infected lifespans, resulting in an optimal
      SPVL~4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain
      observed HIV virulence trends: our model produces SPVL trends with magnitudes
      that are broadly similar to empirical trends. With regard to variation among
      studies in empirical SPVL trends, results from our model suggest that variation
      may be explained by the specific epidemic context, e.g. the mean SPVL of the
      founding lineage or the age of the epidemic; or improvements in HIV screening and
      diagnosis that results in sampling biases. We also use our model to examine
      trends in community viral load, a population-level measure of HIV viral load that
      is thought to reflect a population's overall transmission potential. We find that
      community viral load evolves in association with SPVL, in the absence of
      prevention programs such as antiretroviral therapy, and that the mean community
      viral load is not necessarily a strong predictor of HIV incidence. 

PMID- 24945326
TI  - Reversible corpus callosum splenial lesion due to steroid therapy.
AB  - Reversible corpus callosum splenial (CCS) lesions are rare findings and usually
      detected incidentally. We presented a case of 15-year-old boy with a diagnoses of
      nephrotic syndrome. He was referred for neuropsychiatric symptoms following dose
      reduction on steroid treatment. Brain magnetic resonance imaging (MRI) revealed a
      focal lesion in the CCS, hyperintense on T2 and FLAIR and hypointense on T1
      images with diffusion restriction on apparent diffusion coefficient map. Follow
      up MRI 3 weeks later showed complete resolution of the lesion. It was probably
      result of focal intramyelinic edema due to excytotoxic mechanisms and/or arginine
      vasopressin release. 

PMID- 24945327
TI  - Lysyl oxidase genetic variants affect gene expression in cervical cancer.
AB  - Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays important
      roles in the homeostasis of tumors. The aim of this study was to investigate the
      association between LOX polymorphisms and cervical cancer, and the effect of
      these polymorphisms on gene expression. We evaluated two polymorphisms of LOX,
      rs1800449G/A (G473A) and rs2278226C/G, in 262 cervical cancer cases and 298
      healthy controls in the Chinese population. Results showed that the prevalence of
      rs1800449AA genotype was significantly increased in cases than in controls
      (p=0.004). Individuals who carried the rs1800449A allele had a 1.56-fold
      increased risk for cervical cancer than those with the rs1800449G allele
      (p=0.003). The rs2278226CG genotype also revealed a significantly higher
      proportion in cases (20.6%) than in controls (7.7%, p<0.001). Interestingly, when
      analyzing these two polymorphisms with the serum level of LOX, we identified that
      cervical cancer patients carrying the rs2278226CG genotype had a significantly
      elevated level of LOX than those with rs2278226CC wild type, whereas the same
      phenomenon was not observed in controls. The rs1800449 polymorphism did not
      affect the LOX serum level in either controls or patients. These results suggest
      that the polymorphisms in the LOX gene may be involved in the development of
      cervical cancer through various mechanisms. 

PMID- 24945328
TI  - Transcallosal connection patterns of opposite dorsal premotor regions support a
      lateralized specialization for action and perception.
AB  - Lateralization of higher brain functions requires that a dominant hemisphere
      collects relevant information from both sides. The right dorsal premotor cortex
      (PMd), particularly implicated in visuomotor transformations, was hypothesized to
      be optimally located to converge visuospatial information from both hemispheres
      for goal-directed movement. This was assessed by probabilistic tractography and a
      novel analysis enabling group comparisons of whole-brain connectivity
      distributions of the left and right PMd in standard space (16 human subjects).
      The resulting dominance of contralateral PMd connections was characterized by
      right PMd connections with left visual and parietal areas, indeed supporting a
      dominant role in visuomotor transformations, while the left PMd showed dominant
      contralateral connections with the frontal lobe. Ipsilateral right PMd
      connections were also stronger with posterior parietal regions, relative to the
      left PMd connections, while ipsilateral connections of the left PMd were stronger
      with, particularly, the anterior cingulate, the ventral premotor and anterior
      parietal cortex. The pattern of dominant right PMd connections thus points to a
      specific role in guiding perceptual information into the motor system, while the
      left PMd connections are consistent with action dominance based on a lead in
      motor intention and fine precision skills. 

PMID- 24945330
TI  - Editorial.

PMID- 24945329
TI  - Electrospun DOXY-h loaded-poly(acrylic acid) nanofiber mats: in vitro drug
      release and antibacterial properties investigation.
AB  - Electrospun DOXY-h loaded-poly(acrylic acid) (PAA) nanofiber mats (PAA/DOXY-h
      nanofiber mats) were prepared by the electrospinning technique and post-spinning
      sorption method at various doses: PAA/DOXY-h125, PAA/DOXY-h250, PAA/DOXY-h500,
      and PAA/DOXY-h1000. The morphology, drug content, release characteristics, and
      antibacterial activities of the PAA/DOXY-h nanofiber mats were investigated with
      scanning electron microscopy, UV-vis spectrophotometry, and disc diffusion
      methodology. The PAA/DOXY-h nanofiber mats had a diameter range of 285-340 nm,
      and a smooth surface without beads. Adsorption isotherms of DOXY-h could be
      described well with the Freundlich model. The amounts of DOXY-h, after the post
      spinning sorption process, in the PAA/DOXY-h nanofiber mats ranged between 27.57
      and 101.71 mg/g. All of the PAA/DOXY-h nanofiber mats exhibited an initial burst
      release characteristic with cumulative releasing percentages between 37.14 and
      45.97%, which followed the Fickian diffusion mechanism. Based on the
      antibacterial investigation, the tested gram-positive bacteria, Staphylococcus
      aureus and Streptococcus agalactiae, seemed to be more sensitive to PAA/DOXY-h
      nanofiber mats than the tested gram-negative bacteria, Pseudomonas aeruginosa.
      These PAA/DOXY-h nanofiber mats could be used as an antibacterial wound dressing.

PMID- 24945331
TI  - A comparison of olanzapine versus risperidone for the treatment of schizophrenia:
      a meta-analysis of randomised clinical trials.
AB  - Objective This meta-analysis was carried out to compare the efficacy and safety
      of olanzapine with risperidone in the treatment of schizophrenia. Methods Data
      from randomised, double-blind studies were analysed according to short- (<=12
      weeks) and longer-term (>12 weeks) treatment, and included all-doses analyses and
      a sensitivity analysis of clinically relevant doses. A range of efficacy and
      safety parameters was measured. Results Olanzapine produced statistically
      significant improvements in efficacy and safety parameters compared with
      risperidone over both the short and longer term. Anticholinergic use, study
      dropouts, changes in Positive and Negative Syndrome Scale and Brief Psychiatric
      Rating Scale scores, and Quality-of-Life Scale changes, were often significantly
      in favour of olanzapine. Results from the sensitivity analyses of only clinically
      relevant doses further favoured olanzapine compared with the all-doses analyses.
      Conclusion Small changes in the presence or severity of psychotic symptoms and
      side-effects can affect a patient's prognosis and quality of life. With this in
      mind, the efficacy and safety advantages of olanzapine suggested by this study
      may convey clinical relevance to certain aspects of schizophrenia. However,
      further research - especially into longer-term efficacy and safety - is needed to
      confirm the differences between the available antipsychotics. 

PMID- 24945332
TI  - Efficacy, safety and tolerability of quetiapine: short-term high doses with long
      term follow-up.
AB  - Introduction Quetiapine is effective and well tolerated in the treatment of
      schizophrenia at doses up to 800 mg/day, but data on its use at doses above this
      level are limited. Methods In this open-label study, 35 hospitalised patients
      with schizophrenia, schizoaffective disorder, bipolar disorder or alcohol-induced
      psychosis, who received quetiapine at doses up to 1600 mg/day in a 4-week acute
      phase, were followed for up to 14 months as outpatients. The primary efficacy
      measure was the Clinical Global Impression of Improvement (CGI-I) scale. Results
      At the end of the 4-week hospitalisation period, overall 94.3% of patients had
      experienced improvements in symptoms, with 37.1% "very much improved", 37.1%
      "much improved", and 20% "minimally improved", according to the CGI-I scale. No
      patient experienced a worsening of symptoms during quetiapine treatment and there
      was no change in two (5.7%) patients. Among the 12 patients receiving >800
      mg/day, 10 (83.3%) were "very much" or "much improved". Quetiapine was well
      tolerated: no increase in extrapyramidal symptoms or other adverse events was
      observed even at doses above 800 mg/day, with no changes in safety parameters.
      Conclusion Results indicate that short-term quetiapine therapy at doses up to
      1600 mg/day, with maintenance doses up to 1000 mg/day, may be an effective and
      well-tolerated treatment for patients with psychoses who require high doses of
      antipsychotics for difficult-to-treat symptoms. However, large randomised,
      controlled trials are required to confirm these findings. 

PMID- 24945333
TI  - Psychometric characteristics of the Beck Depression Inventory-II with college
      students of diverse ethnicity.
AB  - Introduction To evaluate the psychometric characteristics of the Beck Depression
      Inventory - Second Edition (BDI-II) with an ethnically diverse sample of college
      students. Methods The BDI-II was completed by a group of 502 college students
      (54% women) with an ethnic distribution of African-American (n=49, 10%), Asian
      American (n=33, 7%), Hispanic (n=113, 22%), Native-American (n=10, 2%), and White
      (n=297, 59%). Psychometric characteristics of the inventory with the ethnically
      diverse group were compared to the results published in the test manual for
      nonclinical samples composed predominantly of European and White participants.
      Results Using confirmatory factor analyses, a three-factor model that identified
      negative attitude, performance difficulty, and somatic dimensions, provides a
      better fit of the data than does the two-factor model. Similar psychometric
      characteristics were found between the ethnically diverse student sample and the
      standardization sample. Based on multivariate analysis of variance, White
      students had higher scores on the item of agitation compared to Asian-American
      students and on the items of worthlessness and irritability compared to Hispanic
      students. Conclusion The results of the psychometric analyses suggest that the
      BDI-II is suitable as a screening instrument for depression in college
      populations of diverse ethnicity. 

PMID- 24945334
TI  - Treatment in risperidone-induced amenorrhoea.
AB  - Objective To find the optimal changes needed for resolution of amenorrhoea
      associated with risperidone. Method Between November 2001 and May 2002, 16 female
      outpatients who had taken risperidone for more than 3 months voluntarily reported
      amenorrhoea. Following each report of amenorrhoea, serum prolactin level was
      measured and treatment changes were undertaken. The menstrual cycles and clinical
      mental status of each patient were followed for the next 6 months. For nine of
      the 16 patients, the dose of risperidone was reduced. For the other seven
      patients, risperidone was switched to olanzapine or quetiapine. Results Fourteen
      of 16 patients had hyperprolactinemia. Two patients who had discontinuation of
      risperidone recovered from amenorrhoea and three of the risperidone-reduction
      patients resumed their periods. All subjects in the drug-switch patients
      recovered. The patients who recovered from amenorrhoea at a reduced dosage of
      risperidone took <=3 mg/day. Two patients in the risperidone-reduction group
      dropped out. Conclusion Stopping risperidone (without starting any other
      antipsychotic) or switching to a prolactin-sparing antipsychotic is an effective
      strategy for resolution of amenorrhoea on risperidone, but that dose reduction is
      rarely effective either because amenorrhoea continues despite lower dose or
      because relapse of psychosis appears. 

PMID- 24945335
TI  - Attitudes to atypical and conventional antipsychotic drug treatment in clinicians
      participating in the cutlass study.
AB  - Objectives To examine clinicians' attitudes regarding the relative benefits and
      risks of conventional and atypical antipsychotic medication, and the perceived
      validity of the CUtLASS study. To examine the attitudes of participant
      clinicians' regarding the operation and administration, and the potential
      clinical impact of the findings. Method Two hundred and sixty-two clinicians were
      each sent an anonymous questionnaire, and invited to indicate whether they agreed
      or disagreed with each of to nine statements (from agree to disagree). Results Of
      the 112 clinicians who responded, 71% supported the CUtLASS study. Thirty-nine
      percent agreed with the statement that the clinical efficacy of atypicals was
      superior to conventional antipsychotics, while 27% disagreed and 34% were
      undecided. Thus, two-thirds of participating clinicians revealed no uncertainty
      on a key question being tested in the CUtLASS study. Further, the vast majority
      (97%) considered that atypicals were associated with less severe side effects.
      Conclusions In clinical studies, recruitment strategies relying on referrals from
      clinicians may find that some clinicians identify fewer patients than expected.
      This can lead to a relatively low yield of potential study subjects and possibly
      a selection bias. Surveys of clinicians approached to participate in clinical
      studies provide a potential mechanism to explore attitudes relevant to
      participant recruitment. 

PMID- 24945336
TI  - Multiple psychiatric diagnoses and self-harm behavior.
AB  - Objective The purpose of this study was to examine among psychiatric inpatients
      (N=110) the relationship, if any, between the number of Axis I diagnoses and the
      number of self-harm behaviors (SHBs). We also wished to explore the role of
      borderline personality disorder (BPD) in mediating this possible relationship.
      Method We examined discharge diagnoses in relationship to scores on the Self-Harm
      Inventory (SHI) for all participants as well as by BPD status. Results For the
      entire sample, there was a significant correlation between the number of Axis I
      disorders and the number of SHBs [Spearman's rho(110)=0.21, p=0.03]. When
      examining this relationship in terms of BPD status, there were no significant
      between-group differences in the number of Axis I diagnoses. While patients
      diagnosed with BPD endorsed significantly more SHBs (M=9.53, SD=3.89) than nonBPD
      patients (M=5.32, SD=3.89), there was only a significant correlation between the
      number of Axis I disorders and SHB for the nonBPD, but not the BPD subsample.
      Conclusions Among psychiatric inpatients, there is a relationship between the
      number of Axis I diagnoses and the number of SHBs. 

PMID- 24945337
TI  - Risperidone in the treatment of behavioural and psychological symptoms of
      dementia in patients diagnosed with vascular or mixed-type dementia.
AB  - Objective Studies have found that the atypical antipsychotic drug, risperidone,
      reduces non-cognitive symptoms, such as aggression, agitation, and psychosis, in
      patients with Alzheimer's disease. This study assessed whether these effects
      extend to patients with vascular or mixed-type dementia. Methods In this
      multicentre, open-label, prospective study, 75 elderly patients with vascular or
      mixed-type dementia and concomitant behavioural and psychological symptoms were
      treated with risperidone for up to 6 months. Results Risperidone decreased the
      frequency and severity of overall behavioural and psychological symptoms, as
      determined by the Neuropsychiatric Inventory, to a mean total score of 7.2+/-0.7
      at end-point compared with 21.0+/-1.5 at baseline (P<0.001). Risperidone improved
      functional capacity (Blessed Dementia Rating Scale, Reisberg's Global
      Deterioration Scale) and depression (Cornell Scale for Depression in Dementia). A
      total of four adverse events (5.3%) were spontaneously reported: two cases of
      hypotension, one of somnolence, and one of paresthesia. Scores on the Udvalg for
      Kliniske Undersogeler extrapyramidal symptom subscale remained stable from
      baseline to end-point. Conclusion Overall, these findings indicate that
      risperidone was effective in reducing behavioural and psychological symptoms and
      was well tolerated, particularly with respect to extrapyramidal symptoms, in this
      elderly population diagnosed with vascular or mixed-type dementia. 

PMID- 24945338
TI  - Prevalence of psychological factors in chronic dermatoses.
AB  - Aim To investigate, retrospectively, psychiatric consultation results of
      inpatients staying in Firat University Dermatology Clinic. Materials and method
      Records of 520 inpatients who were treated in Firat University Dermatology Clinic
      between May 2000 and May 2003 were examined and their psychiatric consultation
      reports were retrospectively evaluated. Results Of the 520 patients who were
      included in the study, 272 were female and 248 were male. Ninety-two patients
      were asked to have psychiatric consultation and when consultation results of
      these patients were examined it was seen that 67 of them (61.7%) were given a
      psychiatric diagnosis. Of the 67 patients who were given a psychiatric diagnosis,
      34 (50.7%) were female and 33 (49.3%) were male. Mean age of the patients was
      39.4 (the youngest being 24 and the oldest 63). It was established that 35.9% of
      patients (24 individuals) were diagnosed as depressive disorder, 29.8% (20
      individuals) as anxiety disorder, 13.4% (nine individuals) as mixed depressive
      anxiety disorder, 13.4% (nine individuals) as borderline personality disorder and
      7.5% (five individuals) as obsessive-compulsive disorder, and that psychiatric
      treatment was started in 91% of patients. Dermatological diagnoses of patients
      who were given psychiatric diagnoses were as follows in order of frequency:
      psoriasis in 22 patients (32.9%), urticaria in 31 patients (46.2%), prurigo
      nodularis in five patients (7.4%) and others in nine patients (13.5%),
      respectively. Conclusions Dermatological diseases and psychiatric disorders
      frequently go together. Psychiatric treatment was started in a high number of
      patients who were given psychiatric diagnoses and had dermatological problems in
      the present study. Referring patients with chronic dermatological problems to the
      psychiatry clinic with a view to supporting their dermatological treatments, we
      believe, will increase the success rate of dermatosis treatment. 

PMID- 24945339
TI  - The combined treatment of venlafaxine and ECT in treatment-resistant depressive
      patients.
AB  - Objective To evaluate the efficacy and safety of the combination treatment of ECT
      and venlafaxine among treatment-resistant depressive patients. Methods We
      reviewed 21 depressive patients who were treated with a combination of
      electroconvulsive therapy (ECT) and venlafaxine. The indication of the ECT
      venlafaxine treatment was inadequate response to at least one antidepressant
      trial of adequate doses and duration. Propofol was used as an anesthetic agent
      during ECT treatments. Results Ninety percent of the patients benefited from the
      combined treatment. The responsivity to the combination treatment was not
      associated with high dose of venlafaxine. In most of the patients, the combined
      treatment was safe and well tolerated. Adverse reactions occurred in 57% of the
      patients and included concentration difficulties (four patients), memory problems
      (seven patients) and headache (one patient). No asystole was observed. Treatment
      was safe with a low dose of venlafaxine equal to or lower than 225 mg/day.
      Conclusions It seems that treatment of ECT combined with low dose venlafaxine and
      propofol as anesthetic agent is effective and safe. This strategy may be a
      therapeutic option in treatment-resistant depressive patients. 

PMID- 24945341
TI  - Jaundice and hepatic enzyme induction during lamotrigine therapy in a bipolar II
      patient.
AB  - Lamotrigine is a novel mood stabiliser as well as an anti-epileptic drug that has
      already been used for the prevention of convulsions. Despite several known side
      effects, hepatic dysfunction related to the drug has not been widely reported. A
      few cases have been observed in neurological, especially paediatric patients, but
      not in psychiatric patients. We report a case of cholestatis which occurred 6
      weeks after starting lamotrigine therapy and which resolved after
      discontinuation, during the acute phase of disease. To the best of our knowledge,
      this is the first case of lamotrigine associated with cholestasis reported in
      patients with bipolar disorder. 

PMID- 24945340
TI  - Prevalence of postnatal depression in Western Nigerian women: a controlled study.
AB  - Objective The objective of this study is to compare the prevalence of depression
      in postpartum women and that of non-postpartum women. Method A total of 876 women
      recruited at 6 weeks postpartum and 900 matched non-postpartum women were
      administered the Beck's Depressive Inventory (BDI) and translated local version
      of the EPDS. Psychiatric diagnosis was made using the using the modified non
      patient version of Structured Clinical Interview for DSM-III-R (SCID-NP). Results
      Depressive disorder was diagnosed in 128 (14.6%) of the postpartum women and in
      55 (6.3%) of the non-postpartum women, and the difference was found to be
      significant (t=8.919, df=875, P<0.001). The postpartum women had higher EPDS and
      BDI scores than the non-postpartum women. The EPDS correlated well with the SCID
      NP diagnosis with a Spearman's correlation of 0.600 (P<0.001) and with the BDI
      score with a Spearman's correlation of 0.461 (P<0.001). The sensitivity of the
      EPDS at cut-off score of 8/9 was 94% and specificity was 97%. Conclusion The
      prevalence of postnatal depression in Nigeria is comparable to that of the
      western world and the Yoruba version of EPDS is a valid instrument for screening
      postnatal women for depressive disorders in a Nigerian community. 

PMID- 24945342
TI  - Hemi-depersonalization syndrome.
AB  - A high variety of factors were found to be implicated in the emergence of
      depersonalization episodes. The remarkable case of a patient who developed a hemi
      depersonalization syndrome is reported in a patient with known obsessive
      compulsive disorder. He complained of feeling his left half of the body as if it
      was detached from him. The part of the body that was perceived as estranged was
      inconsistent with the anatomical distribution of the nervous system as the entire
      left part of his body was concerned, from head to toe. He always remained aware
      that the sensations were not real, and felt like being an outside observer of the
      left side of his body. He also developed an isolated delusional idea. The hemi
      depersonalization syndrome as well as the delusional idea did not respond to
      citalopram 20 mg/day, but remitted rapidly under olanzapine 10 mg/day, the
      obsessive-compulsive symptomatology persisting for several weeks. From the course
      of hemi-depersonalization syndrome and the available literature, it is concluded
      that this syndrome is independent from the concomitant OCD and that the observed
      hemi-depersonalization syndrome is likely to be a manifestation of a psychotic
      reaction which consisted of both the hemi-depersonalization and delusions. 

PMID- 24945343
TI  - Late-onset persistent visual hallucinations with epileptiform discharge.
AB  - We report the case of a 58-year-old female without a history of psychosis or
      epilepsy presenting with abrupt late-onset persistent visual hallucinations that
      had prominent epileptiform discharges with a diffuse sharp and slow wave complex
      on electroencephalography. Except for the visual hallucinations, other psychotic
      symptoms and epileptic seizures, such as disturbance of consciousness and
      convulsion, were not observed. The epileptiform discharge disappeared within 20
      days after initiation of treatment with sodium valproate. Clinical improvement
      commenced after the electroencephalography improvement was complete. The cause
      remains obscure, but it was suggested that there were some organic factors in the
      aetiology of this late-onset visual hallucination. 

PMID- 24945346
TI  - A QM/MM MD insight into photodynamics of hypoxanthine: distinct nonadiabatic
      decay behaviors between keto-N7H and keto-N9H tautomers in aqueous solution.
AB  - Extensive ab initio surface-hopping dynamics simulations have been used to
      explore the excited-state nonadiabatic decay of two biologically relevant
      hypoxanthine keto-N7H and keto-N9H tautomers in aqueous solution. QM/MM
      calculations and QM/MM-based MD simulations predict different hydrogen bonding
      networks around these nucleobase analogues, which influence their photodynamical
      properties remarkably. Furthermore, different solvent effects on the conical
      intersection formation of keto-N7H and keto-N9H were found in excited-state MD
      simulations, which also change the lifetimes of the excited states. In comparison
      with the gas-phase situation, the S1 -> S0 nonradiative decay of keto-N7H is
      slightly faster, while this decay process of keto-N9H becomes much slower in
      water. The presence of pi-electron hydrogen bonds in the solvated keto-N7H is
      considered to facilitate the S1 -> S0 nonradiative decay process.

PMID- 24945345
TI  - Mitochondrial fusion and ERK activity regulate steroidogenic acute regulatory
      protein localization in mitochondria.
AB  - The rate-limiting step in the biosynthesis of steroid hormones, known as the
      transfer of cholesterol from the outer to the inner mitochondrial membrane, is
      facilitated by StAR, the Steroidogenic Acute Regulatory protein. We have
      described that mitochondrial ERK1/2 phosphorylates StAR and that mitochondrial
      fusion, through the up-regulation of a fusion protein Mitofusin 2, is essential
      during steroidogenesis. Here, we demonstrate that mitochondrial StAR together
      with mitochondrial active ERK and PKA are necessary for maximal steroid
      production. Phosphorylation of StAR by ERK is required for the maintenance of
      this protein in mitochondria, observed by means of over-expression of a StAR
      variant lacking the ERK phosphorylation residue. Mitochondrial fusion regulates
      StAR levels in mitochondria after hormone stimulation. In this study, Mitofusin 2
      knockdown and mitochondrial fusion inhibition in MA-10 Leydig cells diminished
      StAR mRNA levels and concomitantly mitochondrial StAR protein. Together our
      results unveil the requirement of mitochondrial fusion in the regulation of the
      localization and mRNA abundance of StAR. We here establish the relevance of
      mitochondrial phosphorylation events in the correct localization of this key
      protein to exert its action in specialized cells. These discoveries highlight the
      importance of mitochondrial fusion and ERK phosphorylation in cholesterol
      transport by means of directing StAR to the outer mitochondrial membrane to
      achieve a large number of steroid molecules per unit of StAR. 

PMID- 24945347
TI  - TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in
      a murine hind limb ischemia model.
AB  - AIMS: We investigated the role of the TLR4-accessory molecule RP105 (CD180) in
      post-ischemic neovascularization, i.e. arteriogenesis and angiogenesis. TLR4
      mediated activation of pro-inflammatory Ly6Chi monocytes is crucial for effective
      neovascularization. Immunohistochemical analyses revealed that RP105+ monocytes
      are present in the perivascular space of remodeling collateral arterioles. As
      RP105 inhibits TLR4 signaling, we hypothesized that RP105 deficiency would lead
      to an unrestrained TLR4-mediated inflammatory response and hence to enhanced
      blood flow recovery after ischemia. METHODS AND RESULTS: RP105-/- and wild type
      (WT) mice were subjected to hind limb ischemia and blood flow recovery was
      followed by Laser Doppler Perfusion Imaging. Surprisingly, we found that blood
      flow recovery was severely impaired in RP105-/- mice. Immunohistochemistry showed
      that arteriogenesis was reduced in these mice compared to the WT. However, both
      in vivo and ex vivo analyses showed that circulatory pro-arteriogenic Ly6Chi
      monocytes were more readily activated in RP105-/- mice. FACS analyses showed that
      Ly6Chi monocytes became activated and migrated to the affected muscle tissues in
      WT mice following induction of hind limb ischemia. Although Ly6Chi monocytes were
      readily activated in RP105-/- mice, migration into the ischemic tissues was
      hampered and instead, Ly6Chi monocytes accumulated in their storage compartments,
      bone marrow and spleen, in RP105-/- mice. CONCLUSIONS: RP105 deficiency results
      in an unrestrained inflammatory response and monocyte over-activation, most
      likely due to the lack of TLR4 regulation. Inappropriate, premature systemic
      activation of pro-inflammatory Ly6Chi monocytes results in reduced infiltration
      of Ly6Chi monocytes in ischemic tissues and in impaired blood flow recovery.

PMID- 24945348
TI  - HCV viral decline at week 2 of Peg-IFN-alpha-2a/RBV therapy as a predictive tool
      for tailoring treatment in HIV/HCV genotype 1 co-infected patients.
AB  - BACKGROUND: Optimizing HCV genotype 1 therapy in terms of response prediction and
      tailoring treatment is undoubtedly the cornerstone of treating HIV co-infected
      patients in clinical practice. Accordingly, our aim was to analyze the predictive
      value of HCV viral decline for sustained virological response (SVR), measured at
      a time point as early as week 2 of therapy with pegylated interferon alpha-2a
      plus ribavirin (Peg-IFN/RBV). METHODS: Previously untreated HIV/HCV genotype 1 co
      infected patients were included in this study. The HCV RNA titer was measured at
      week 2 after starting treatment with Peg-IFN/RBV. The likelihood of reaching SVR
      when HCV RNA viral titers declined at week 2 was evaluated relative to predictive
      baseline factors. RESULTS: A total of 192 HIV/HCV genotype-1 co-infected patients
      were enrolled in the study and began therapy. One hundred and sixty-three
      patients completed a full course of Peg-IFN/RBV treatment for 2 weeks and 59 of
      these (36.2%) reached SVR. An HCV RNA viral load decline of >=1.5 log IU/mL at
      week 2 had the maximum positive predictive value for SVR (83.3%; 95% CI: 68.5%
      92.9%) and was identified as the strongest independent predictive factor for
      reaching SVR across all baseline predictive factors. CONCLUSIONS: HCV viral
      decline at week 2 had a high predictive value for identifying patients with a
      high and low likelihood of reaching SVR using dual therapy, regardless of strong
      predictive baseline factors. This finding may be useful for developing a
      predictive tool to help tailor HCV genotype 1 therapy in HIV co-infected
      patients.

PMID- 24945349
TI  - Phospholipase C-related catalytically inactive protein (PRIP) regulates lipolysis
      in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase.
AB  - Phosphorylation of hormone-sensitive lipase (HSL) and perilipin by protein kinase
      A (PKA) promotes the hydrolysis of lipids in adipocytes. Although activation of
      lipolysis by PKA has been well studied, inactivation via protein phosphatases is
      poorly understood. Here, we investigated whether phospholipase C-related
      catalytically inactive protein (PRIP), a binding partner for protein phosphatase
      1 and protein phosphatase 2A (PP2A), is involved in lipolysis by regulating
      phosphatase activity. PRIP knockout (PRIP-KO) mice displayed reduced body-fat
      mass as compared with wild-type mice fed with standard chow ad libitum. Most
      other organs appeared normal, suggesting that mutant mice had aberrant fat
      metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated
      compared to that in wild-type mice. Starvation of wild-type mice or stimulation
      of adipose tissue explants with the catabolic hormone, adrenaline, translocated
      both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of
      PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the
      phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes
      was significantly reduced and was independent of adrenaline stimulation.
      Lipolysis activity, as assessed by measurement of non-esterified fatty acids and
      glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were
      treated with a phosphatase inhibitor, they showed a high lipolysis activity at
      the similar level to PRIP-KO adipocytes. Collectively, these results suggest that
      PRIP promotes the translocation of phosphatases to lipid droplets to trigger the
      dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis. 

PMID- 24945351
TI  - Aboveground tree growth varies with belowground carbon allocation in a tropical
      rainforest environment.
AB  - Young secondary forests and plantations in the moist tropics often have rapid
      rates of biomass accumulation and thus sequester large amounts of carbon. Here,
      we compare results from mature forest and nearby 15-20 year old tree plantations
      in lowland Costa Rica to evaluate differences in allocation of carbon to
      aboveground production and root systems. We found that the tree plantations,
      which had fully developed, closed canopies, allocated more carbon belowground -
      to their root systems - than did mature forest. This increase in belowground
      carbon allocation correlated significantly with aboveground tree growth but not
      with canopy production (i.e., leaf fall or fine litter production). In contrast,
      there were no correlations between canopy production and either tree growth or
      belowground carbon allocation. Enhanced allocation of carbon to root systems can
      enhance plant nutrient uptake, providing nutrients beyond those required for the
      production of short-lived tissues such as leaves and fine roots, and thus
      enabling biomass accumulation. Our analyses support this deduction at our site,
      showing that enhanced allocation of carbon to root systems can be an important
      mechanism promoting biomass accumulation during forest growth in the moist
      tropics. Identifying factors that control when, where and for how long this
      occurs would help us to improve models of forest growth and nutrient cycling, and
      to ascertain the role that young forests play in mitigating increased atmospheric
      carbon dioxide. 

PMID- 24945350
TI  - Invariant NKT cell response to dengue virus infection in human.
AB  - BACKGROUND: Dengue viral infection is a global health threat without vaccine or
      specific treatment. The clinical outcome varies from asymptomatic, mild dengue
      fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune
      responses were found to be detrimental in the dengue pathogenesis, the roles of
      earlier innate events remain largely uninvestigated. Invariant natural killer T
      (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive
      response but their role in human dengue virus infection is not known. We
      hypothesized that iNKT cells play a role in human dengue infection. METHODS:
      Blood samples from a well-characterized cohort of children with DF, DHF, in
      comparison to non-dengue febrile illness (OFI) and healthy controls at various
      time points were studied. iNKT cells activation were analyzed by the expression
      of CD69 by flow cytometry. Their cytokine production was then analyzed after
      alpha-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69
      expression on conventional T cells were measured. RESULTS: iNKT cells were
      activated during acute dengue infection. The level of iNKT cell activation
      associates with the disease severity. Furthermore, these iNKT cells had altered
      functional response to subsequent ex vivo stimulation with alpha-GalCer.
      Moreover, during acute dengue infection, monocytic CD1d expression was also
      upregulated and conventional T cells also became activated. CONCLUSION: iNKT
      cells might play an early and critical role in the pathogenesis of severe dengue
      viral infection in human. Targeting iNKT cells and CD1d serve as a potential
      therapeutic strategy for severe dengue infection in the future.

PMID- 24945352
TI  - Characterization of spectrum, de novo rate and genotype-phenotype correlation of
      dominant GJB2 mutations in Chinese hans.
AB  - Dominant mutations in GJB2 may lead to various degrees of sensorineural hearing
      impairment and/or hyperproliferative epidermal disorders. So far studies of
      dominant GJB2 mutations were mostly limited to case reports of individual
      patients and families. In this study, we identified 7 families, 11 subjects with
      dominant GJB2 mutations by sequencing of GJB2 in 2168 Chinese Han probands with
      sensorineural hearing impairment and characterized the associated spectrum, de
      novo rate and genotype-phenotype correlation. We identified p.R75Q, p.R75W and
      p.R184Q as the most frequent dominant GJB2 mutations among Chinese Hans, which
      had a very high de novo rate (71% of probands). A majority (10/11) of subjects
      carrying dominant GJB2 mutations exhibited palmoplantar keratoderma in addition
      to hearing impairment. In two families segregated with additional c.235delC or
      p.V37I mutations of GJB2, family members with the compound heterozygous mutations
      exhibited more severe phenotype than those with single dominant GJB2 mutation.
      Our study suggested that the high de novo mutation rate gives rise to a
      significant portion of dominant GJB2 mutations. The severity of the hearing and
      epidermal phenotypes associated with dominant GJB2 mutations may be modified by
      additional recessive mutations of GJB2. 

PMID- 24945353
TI  - Recruitment of RED-SMU1 complex by Influenza A Virus RNA polymerase to control
      Viral mRNA splicing.
AB  - Influenza A viruses are major pathogens in humans and in animals, whose genome
      consists of eight single-stranded RNA segments of negative polarity. Viral mRNAs
      are synthesized by the viral RNA-dependent RNA polymerase in the nucleus of
      infected cells, in close association with the cellular transcriptional machinery.
      Two proteins essential for viral multiplication, the exportin NS2/NEP and the ion
      channel protein M2, are produced by splicing of the NS1 and M1 mRNAs,
      respectively. Here we identify two human spliceosomal factors, RED and SMU1, that
      control the expression of NS2/NEP and are required for efficient viral
      multiplication. We provide several lines of evidence that in infected cells, the
      hetero-trimeric viral polymerase recruits a complex formed by RED and SMU1
      through interaction with its PB2 and PB1 subunits. We demonstrate that the
      splicing of the NS1 viral mRNA is specifically affected in cells depleted of RED
      or SMU1, leading to a decreased production of the spliced mRNA species NS2, and
      to a reduced NS2/NS1 protein ratio. In agreement with the exportin function of
      NS2, these defects impair the transport of newly synthesized viral
      ribonucleoproteins from the nucleus to the cytoplasm, and strongly reduce the
      production of infectious influenza virions. Overall, our results unravel a new
      mechanism of viral subversion of the cellular splicing machinery, by establishing
      that the human splicing factors RED and SMU1 act jointly as key regulators of
      influenza virus gene expression. In addition, our data point to a central role of
      the viral RNA polymerase in coupling transcription and alternative splicing of
      the viral mRNAs. 

PMID- 24945357
TI  - Young adults, social networks, and addiction recovery: post treatment changes in
      social ties and their role as a mediator of 12-step participation.
AB  - BACKGROUND: Social factors play a key role in addiction recovery. Research with
      adults indicates individuals with substance use disorder (SUD) benefit from
      mutual-help organizations (MHOs), such as Alcoholics Anonymous, via their ability
      to facilitate adaptive network changes. Given the lower prevalence of sobriety
      conducive, and sobriety-supportive, social contexts in the general population
      during the life-stage of young adulthood, however, 12-step MHOs may play an even
      more crucial recovery-supportive social role for young adults, but have not been
      investigated. Greater knowledge could enhance understanding of recovery-related
      change and inform young adults' continuing care recommendations. METHODS:
      Emerging adults (N = 302; 18-24 yrs; 26% female; 95% White) enrolled in a study
      of residential treatment effectiveness were assessed at intake, 1, 3, 6, and 12
      months on 12-step attendance, peer network variables ("high [relapse] risk" and
      "low [relapse] risk" friends), and treatment outcomes (Percent Days Abstinent;
      Percent Days Heavy Drinking). Hierarchical linear models tested for change in
      social risk over time and lagged mediational analyses tested whether 12-step
      attendance conferred recovery benefits via change in social risk. RESULTS: High
      risk friends were common at treatment entry, but decreased during follow-up; low
      risk friends increased. Contrary to predictions, while substantial recovery
      supportive friend network changes were observed, this was unrelated to 12-step
      participation and, thus, not found to mediate its positive influence on outcome.
      CONCLUSIONS: Young adult 12-step participation confers recovery benefit; yet,
      while encouraging social network change, 12-step MHOs may be less able to provide
      social network change directly for young adults, perhaps because similar-aged
      peers are less common in MHOs. Findings highlight the importance of both social
      networks and 12-step MHOs and raise further questions as to how young adults
      benefit from 12-step MHOs.

PMID- 24945355
TI  - Digital genotyping of macrosatellites and multicopy genes reveals novel
      biological functions associated with copy number variation of large tandem
      repeats.
AB  - Tandem repeats are common in eukaryotic genomes, but due to difficulties in
      assaying them remain poorly studied. Here, we demonstrate the utility of
      Nanostring technology as a targeted approach to perform accurate measurement of
      tandem repeats even at extremely high copy number, and apply this technology to
      genotype 165 HapMap samples from three different populations and five species of
      non-human primates. We observed extreme variability in copy number of tandemly
      repeated genes, with many loci showing 5-10 fold variation in copy number among
      humans. Many of these loci show hallmarks of genome assembly errors, and the true
      copy number of many large tandem repeats is significantly under-represented even
      in the high quality 'finished' human reference assembly. Importantly, we
      demonstrate that most large tandem repeat variations are not tagged by nearby
      SNPs, and are therefore essentially invisible to SNP-based GWAS approaches. Using
      association analysis we identify many cis correlations of large tandem repeat
      variants with nearby gene expression and DNA methylation levels, indicating that
      variations of tandem repeat length are associated with functional effects on the
      local genomic environment. This includes an example where expansion of a
      macrosatellite repeat is associated with increased DNA methylation and
      suppression of nearby gene expression, suggesting a mechanism termed "repeat
      induced gene silencing", which has previously been observed only in transgenic
      organisms. We also observed multiple signatures consistent with altered selective
      pressures at tandemly repeated loci, suggesting important biological functions.
      Our studies show that tandemly repeated loci represent a highly variable fraction
      of the genome that have been systematically ignored by most previous studies,
      copy number variation of which can exert functionally significant effects. We
      suggest that future studies of tandem repeat loci will lead to many novel
      insights into their role in modulating both genomic and phenotypic diversity. 

PMID- 24945358
TI  - Identifying crucial parameter correlations maintaining bursting activity.
AB  - Recent experimental and computational studies suggest that linearly correlated
      sets of parameters (intrinsic and synaptic properties of neurons) allow central
      pattern-generating networks to produce and maintain their rhythmic activity
      regardless of changing internal and external conditions. To determine the role of
      correlated conductances in the robust maintenance of functional bursting
      activity, we used our existing database of half-center oscillator (HCO) model
      instances of the leech heartbeat CPG. From the database, we identified functional
      activity groups of burster (isolated neuron) and half-center oscillator model
      instances and realistic subgroups of each that showed burst characteristics
      (principally period and spike frequency) similar to the animal. To find linear
      correlations among the conductance parameters maintaining functional leech
      bursting activity, we applied Principal Component Analysis (PCA) to each of these
      four groups. PCA identified a set of three maximal conductances (leak current,
      [Formula: see text]Leak; a persistent K current, [Formula: see text]K2; and of a
      persistent Na+ current, [Formula: see text]P) that correlate linearly for the two
      groups of burster instances but not for the HCO groups. Visualizations of HCO
      instances in a reduced space suggested that there might be non-linear
      relationships between these parameters for these instances. Experimental studies
      have shown that period is a key attribute influenced by modulatory inputs and
      temperature variations in heart interneurons. Thus, we explored the sensitivity
      of period to changes in maximal conductances of [Formula: see text]Leak,
      [Formula: see text]K2, and [Formula: see text]P, and we found that for our
      realistic bursters the effect of these parameters on period could not be assessed
      because when varied individually bursting activity was not maintained. 

PMID- 24945359
TI  - Design of embedded-hybrid antimicrobial peptides with enhanced cell selectivity
      and anti-biofilm activity.
AB  - Antimicrobial peptides have attracted considerable attention because of their
      broad-spectrum antimicrobial activity and their low prognostic to induce
      antibiotic resistance which is the most common source of failure in bacterial
      infection treatment along with biofilms. The method to design hybrid peptide
      integrating different functional domains of peptides has many advantages. In this
      study, we designed an embedded-hybrid peptide R-FV-I16 by replacing a functional
      defective sequence RR7 with the anti-biofilm sequence FV7 embedded in the middle
      position of peptide RI16. The results demonstrated that the synthetic hybrid the
      peptide R-FV-I16 had potent antimicrobial activity over a wide range of Gram
      negative and Gram-positive bacteria, as well as anti-biofilm activity. More
      importantly, R-FV-I16 showed lower hemolytic activity and cytotoxicity.
      Fluorescent assays demonstrated that R-FV-I16 depolarized the outer and the inner
      bacterial membranes, while scanning electron microscopy and transmission electron
      microscopy further indicated that this peptide killed bacterial cells by
      disrupting the cell membrane, thereby damaging membrane integrity. Results from
      SEM also provided evidence that R-FV-I16 inherited anti-biofilm activity from the
      functional peptide sequence FV7. Embedded-hybrid peptides could provide a new
      pattern for combining different functional domains and showing an effective
      avenue to screen for novel antimicrobial agents. 

PMID- 24945361
TI  - Fixed partial denture treatment with mini dental implants.

PMID- 24945360
TI  - Vampire bats and rabies: toward an ecological solution to a public health
      problem.

PMID- 24945362
TI  - Use of versican variant V3 and versican antisense expression to engineer cultured
      human skin containing increased content of insoluble elastin.
AB  - Skin substitutes for repair of dermal wounds are deficient in functional elastic
      fibres. We report that the content of insoluble elastin in the dermis of cultured
      human skin can be increased though the use of two approaches that enhance
      elastogenesis by dermal fibroblasts, forced expression of versican variant V3,
      which lacks glycosaminoglycan (GAG) chains, and forced expression of versican
      antisense to decrease levels of versican variant V1 with GAG chains. Human dermal
      fibroblasts transduced with V3 or anti-versican were cultured under standard
      conditions over a period of 4 weeks to produce dermal sheets, with growth
      enhanced though multiple seedings for the first 3 weeks. Human keratinocytes,
      cultured in supplemented media, were added to the 4-week dermal sheets and the
      skin layer cultured for a further week. At 5 weeks, keratinocytes were
      multilayered and differentiated, with desmosome junctions thoughout and keratin
      deposits in the upper squamous layers. The dermal layer was composed of layered
      fibroblasts surrounded by extracellular matrix of collagen bundles and, in
      control cultures, small scattered elastin deposits. Forced expression of V3 and
      versican antisense slowed growth, decreased versican V1 expression, increased
      tropoelastin expression and/or the deposition of large aggregates of insoluble
      elastin in the dermal layer, and increased tissue stiffness, as measured by nano
      indentation. Skin sheets were also cultured on Endoform Dermal TemplateTM, the
      biodegradable wound dressing made from the lamina propria of sheep foregut. Skin
      structure and the enhanced deposition of elastin by forced expression of V3 and
      anti-versican were preserved on this supportive substrate. Copyright (c) 2014
      John Wiley & Sons, Ltd.

PMID- 24945363
TI  - Profession differences in family focused practice in the adult mental health
      system.
AB  - There is a large gulf between what psychiatric services should (or could) provide
      and what they do in practice. This article sought to determine practice
      differences between the differing professions working in adult mental health
      services in terms of their family focused work. Three hundred and seven adult
      mental health professionals completed a cross-sectional survey of family focused
      practices in adult mental health services. Findings highlight that social workers
      engaged in more family focused practice compared to psychiatric nurses, who
      performed consistently the lowest on direct family care, compared to both social
      workers and psychologists. Clear skill, knowledge, and confidence differences are
      indicated between the professions. The article concludes by offering direction
      for future profession education and training in family focused practices. 

PMID- 24945364
TI  - Impact depth and the interaction with impact speed affect the severity of
      contusion spinal cord injury in rats.
AB  - Spinal cord injury (SCI) biomechanics suggest that the mechanical factors of
      impact depth and speed affect the severity of contusion injury, but their
      interaction is not well understood. The primary aim of this work was to examine
      both the individual and combined effects of impact depth and speed in contusion
      SCI on the cervical spinal cord. Spinal cord contusions between C5 and C6 were
      produced in anesthetized rats at impact speeds of 8, 80, or 800 mm/s with
      displacements of 0.9 or 1.5 mm (n=8/group). After 7 days postinjury, rats were
      assessed for open-field behavior, euthanized, and spinal cords were harvested.
      Spinal cord tissue sections were stained for demyelination (myelin-based protein)
      and tissue sparing (Luxol fast blue). In parallel, a finite element model of rat
      spinal cord was used to examine the resulting maximum principal strain in the
      spinal cord during impact. Increasing impact depth from 0.9 to 1.5 mm reduced
      open-field scores (p<0.01) above 80 mm/s, reduced gray (GM) and white matter (WM)
      sparing (p<0.01), and increased the amount of demyelination (p<0.01). Increasing
      impact speed showed similar results at the 1.5-mm impact depth, but not the 0.9
      mm impact depth. Linear correlation analysis with finite element analysis strain
      showed correlations (p<0.001) with nerve fiber damage in the ventral (R(2)=0.86)
      and lateral (R(2)=0.74) regions of the spinal cord and with WM (R(2)=0.90) and GM
      (R(2)=0.76) sparing. The results demonstrate that impact depth is more important
      in determining the severity of SCI and that threshold interactions exist between
      impact depth and speed.

PMID- 24945365
TI  - A large multi-pathogen gastroenteritis outbreak caused by drinking contaminated
      water from antique neighbourhood fountains, Erzurum city, Turkey, December 2012.
AB  - We investigated a gastroenteritis outbreak in Erzurum city, Turkey in December
      2012 to identify its cause and mode of transmission. We defined a probable case
      as onset of diarrhoea (?3 episodes/day) or vomiting, plus fever or nausea or
      abdominal pain during 19-27 December, 2012 in an Erzurum city resident. In a case
      control study we compared exposures of 95 randomly selected probable cases and 95
      neighbourhood-matched controls. We conducted bacterial culture and real-time
      multiplex PCR for identification of pathogens. During the week before illness
      onset, 72% of cases and 15% of controls only drank water from antique
      neighbourhood fountains; conversely, 16% of cases and 65% of controls only drank
      bottled or tap water (adjusted odds ratio 20, 95% confidence interval 4.6-84,
      after controlling for age and sex using conditional logistic regression). Of
      eight stool specimens collected, two were positive for Shigella sonnei, one for
      astrovirus, one for astrovirus and norovirus, and one for astrovirus and
      rotavirus. Water samples from the fountains had elevated total coliform (38
      300/100 ml) and Escherichia coli (22-198/100 ml) counts. In conclusion, drinking
      contaminated fountain water caused this multi-pathogen outbreak. Residents should
      stop drinking water from these fountains, and clean water from the water
      treatment plant should be connected to the fountains.

PMID- 24945366
TI  - Wearable multi-channel microelectrode membranes for elucidating
      electrophysiological phenotypes of injured myocardium.
AB  - Understanding the regenerative capacity of small vertebrate models has provided
      new insights into the plasticity of injured myocardium. Here, we demonstrate the
      application of flexible microelectrode arrays (MEAs) in elucidating
      electrophysiological phenotypes of zebrafish and neonatal mouse models of heart
      regeneration. The 4-electrode MEA membranes were designed to detect electrical
      signals in the aquatic environment. They were micro-fabricated to adhere to the
      non-planar body surface of zebrafish and neonatal mice. The acquired signals were
      processed to display an electrocardiogram (ECG) with high signal-to-noise-ratios,
      and were validated via the use of conventional micro-needle electrodes. The 4
      channel MEA provided signal stability and spatial resolution, revealing the site
      specific electrical injury currents such as ST-depression in response to
      ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes
      provided electrophysiological insights into long-term conduction phenotypes for
      small vertebral models of heart injury and regeneration with a translational
      implication for monitoring cardiac patients. 

PMID- 24945367
TI  - Study on variation of lipids during different growth phases of living
      cyanobacteria using easy ambient sonic-spray ionization mass spectrometry.
AB  - Lipids are important components of cell membranes and thylakoids in
      cyanobacteria, and they play vital roles in various biological activities. Real
      time tracing of the variation of membrane lipids can provide insights of the
      physiological status of cyanobacterial cells. In this work, easy ambient sonic
      spray ionization mass spectrometry (EASI-MS) was utilized to investigate the
      changes of acidic lipids in unicellular (Synechocystis 6803, Synechococcus 7002)
      and filamentous (Anabaena 7120) cyanobacteria during different growth phases. A
      sqdX mutant with a reduced synthesis of sulfoquinovosyl diacylglycerol (SQDG) was
      constructed to verify the acquired data of EASI-MS. Principal component analysis
      (PCA) was performed to compare the acquired data, enabling the discrimination of
      different species of cyanobacteria in day-to-day analysis. The results showed
      that the three representative cyanobacteria and their growth status can be easily
      determined on the basis of the lipids components detected by EASI-MS. Very
      interestingly, significant decreases of the ratios of SQDG/PG and dramatic
      changes of the unsaturation level of lipids were observed in different culture
      times in these cyanobacteria, and these two unique characters can be used
      describe the aging of cyanobacteria. 

PMID- 24945368
TI  - Clinical Value of 18F-FDG PET/CT in Detecting Adrenal Metastasis in Patients with
      Hepatocellular Carcinoma.
AB  - The purpose of this study was to evaluate the accuracy of (18)F-FDG PET/CT scans
      in detecting adrenal metastasis in liver transplant candidates with
      hepatocellular carcinoma (HCC). A total of 166 patients diagnosed with HCC
      received (18)F-FDG PET/CT imaging before liver transplantation. Of these
      patients, 5 patients (4 males, 1 female; median age: 51.2 y, range: 33-61 y) were
      found to have suspected adrenal metastases and were included in this study. Two
      cases (Cases 1 and 5) underwent an (18)F-FDG PET/CT scan at the initial stage, 3
      cases (Cases 2-4) underwent an (18)F-FDG PET/CT scan for restaging, and one case
      (Case 5) underwent a second (18)F-FDG PET/CT scan for evaluating treatment
      response. Among the 8 lesions, there was one false-negative metastatic lesion
      (Lesion 4, Case 3) and one false-positive adrenal gland lesion (Lesion 7, Case 5)
      when compared with either histopathologic reports or established clinical and
      imaging follow-up results. In general, (18)F-FDG PET/CT scans have limitations
      that make it difficult to distinguish between malignant and benign lesions in
      adrenal glands that are based only on quantitative values measured using the
      (18)F-FDG PET/CT scan. 

PMID- 24945369
TI  - Effect of Scanning Beam for Superficial Dose in Proton Therapy.
AB  - Proton beam delivery technology is under development to minimize the scanning
      spot size for uniform dose to target, but it is also known that the superficial
      dose could be as high as the dose at Bragg peak for narrow and small proton
      beams. The objective of this study is to explore the characteristics of dose
      distribution at shallow depths using Monte Carlo simulation with the FLUKA code
      for uniform scanning (US) and discrete spot scanning (DSS) proton beams. The
      results show that the superficial dose for DSS is relatively high compared to US.
      Additionally, DSS delivers a highly heterogeneous dose to the irradiated surface
      for comparable doses at Bragg peak. Our simulation shows that the superficial
      dose can become as high as the Bragg peak when the diameter of the proton beam is
      reduced. This may compromise the advantage of proton beam therapy for sparing
      normal tissue, making skin dose a limiting factor for the clinical use of DSS.
      Finally, the clinical advantage of DSS may not be essential for treating uniform
      dose across a large target, as in craniospinal irradiation (CSI). 

PMID- 24945370
TI  - Endobronchial/Endoesophageal Ultrasound (EBUS/EUS) Guided Fine Needle Aspiration
      (FNA) and 18F-FDG PET/CT Scanning in Restaging of Locally Advanced Non-small Cell
      Lung Cancer (NSCLC) Treated with Chemo-radiotherapy: A Mono-institutional Pilot
      Experience.
AB  - Chemo-radiotherapy is standard treatment of stage IIIA-N2 bulky or IIIB non-small
      cell lung cancer (NSCLC). Surgical resection of residual disease in downstaged
      patients may improve overall survival. In this setting, restaging disease is
      still a challenge. 18F-FDG PET/CT represents the gold standard although accuracy
      results are disappointing. Endoscopic bronchial/ esophageal ultrasound (EBUS/EUS)
      guided fine needle aspiration (FNA) may confirm lymph node (LN) involvement. We
      analyzed 16 patients with stage IIIA-N2 bulky or IIIB NSCLC treated with chemo
      radiotherapy. At restaging, all patients performed EBUS/EUS with FNA and PET/CT
      scan and results were compared. Patients underwent PET/CT scan 43 days (range: 24
      89) and EBUS/EUS 42 days (range: 14-71) after therapy. Overall, 7 EBUS and 9 EUS
      procedures were performed: no complications resulting from the procedure
      occurred. In 6 patients EBUS/EUS did not reveal any suspicious lesions; in 2 the
      exam showed enlarged mediastinal LN that were biopsied, but with no evidence of
      tumor cells; in 2 the sample was not considered diagnostic; 6 had persistent
      mediastinal LN involvement. PET/CT scan showed 4 cases of complete metabolic
      response, 9 partial metabolic response, 2 stable metabolic disease and one
      progressive metabolic disease. Notably, all 7 patients with .80% decrease in SUV
      with respect to basal value showed a pathological complete response or negative
      EBUS/EUS. EBUS/EUS could be used to complement PET/CT scanning to verify
      mediastinal LN clearance. Further prospective trials are warranted to confirm the
      utility of EBUS/EUS together with PET/CT in restaging locally advanced NSCLC. 

PMID- 24945371
TI  - Quality Assurance Results for a Commercial Radiosurgery System: A Communication.
AB  - The purpose of this communication is to inform the radiosurgery community of
      quality assurance (QA) results requiring attention in a commercial FDA-approved
      linac-based cone stereo-tactic radiosurgery (SRS) system. Standard published QA
      guidelines as per the American Association of Physics in Medicine (AAPM) were
      followed during the SRS system's commissioning process including end-to-end
      testing, cone concentricity testing, image transfer verification, and
      documentation. Several software and hardware deficiencies that were deemed risky
      were uncovered during the process and QA processes were put in place to mitigate
      these risks during clinical practice. In particular, the present work focuses on
      daily cone concentricity testing and commissioning-related findings associated
      with the software. Cone concentricity/alignment is measured daily using both
      optical light field inspection, as well as quantitative radiation field tests
      with the electronic portal imager. In 10 out of 36 clini-cal treatments,
      adjustments to the cone position had to be made to align the cone with the
      collimator axis to less than 0.5 mm and on two occasions the pre-adjustment
      measured offset was 1.0 mm. Software-related errors discovered during
      commissioning included incorrect transfer of the isocentre in DICOM coordinates,
      improper handling of non-axial image sets, and complex handling of beam data,
      especially for multi-target treatments. QA processes were established to mitigate
      the occurrence of the software errors. With proper QA processes, the reported SRS
      system complies with tolerances set out in established guidelines. Discussions
      with the vendor are ongoing to address some of the hardware issues related to
      cone alignment. 

PMID- 24945372
TI  - Semi-spherical Radiofrequency Bipolar Device - A New Technique for Liver
      Resection: Experimental In Vivo Study on the Porcine Model.
AB  - The incidence of colorectal carcinoma is still growing in the Czech Republic and
      also all around the world. With success of oncological treatment is also growing
      a number of potential patients with liver metastases, who can profit from
      surgical therapy. The aim of this study was to confirm on porcine models that
      this method by using new surgical device is effective and safe for patients who
      have to undergo liver resection. The primary hypothesis of the study was to
      evaluate whether this new device is able to consistently produce homogeneous and
      predictable areas of coagulation necrosis without the Pringle maneuver of
      vascular inflow occlusion. The secondary hypothesis of the study was to compare
      the standard linear radiofrequency device and a new semi-spherical bipolar device
      for liver ablation and resection in a hepatic porcine model. Twelve pigs were
      randomly divided into two groups. Each pig underwent liver resection from both
      liver lobes in the marginal, thinner part of liver parenchyma. The pigs in first
      group were operated with standard using device and in the second group we used
      new developed semi-spherical device. We followed blood count in 0(th), 14(th) and
      30(th) day from operation. 14(th) day from resection pigs underwent diagnostic
      laparoscopy to evaluate of their state, and 30(th) day after operation were all
      pigs euthanized and subjected to histopathological examination. Histopathological
      evaluation of thermal changes at the resection margin showed strong thermal
      alteration in both groups. Statistical analysis of collected dates did not prove
      any significant (p < 0.05) differences between standard using device and our new
      surgical tool. We proved safety of new designed semi-spherical surgical. This
      device can offer the possibility of shortening the ablation time and operating
      time, which is benefit for patients undergoing the liver resection. 

PMID- 24945373
TI  - Serenoa Repens Induces Growth Arrest, Apoptosis and Inactivation of STAT3
      Signaling in Human Glioma Cells.
AB  - Serenoa repens, the extract of berry in Southeastern United States, is one of
      several phytotherapeutic agents available for the treatment of Benign prostatic
      hyperplasia (BPH). In this study, we found for the first time that Serenoa repens
      effectively inhibited the growth of human U87 and U251 glioma cells. Flow
      cytometry assay showed that Serenoa repens induced apoptosis of U87 and U251
      glioma cells in a dose-dependent manner. Also, Serenoa repens increased the
      expression of cleaved-PARP, Caspase-3 or p27 protein in these two cell lines,
      respectively. In addition, we found that Serenoa repens down-regulated basal
      level of phosphorylated form of signal transducer and activator of transcription
      3 (STAT 3) in both U87 and U251 glioma cells. Furthermore, it was discovered that
      a Janus family of tyrosine kinase (JAK) inhibitor AG490 inhibit the growth of
      human U87 and U251 glioma cells and AG490 enhanced the ability of Serenoa repens
      to inhibit the growth of U87 and U251 glioma cells as measured by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These results
      indicate that Serenoa repens reduces the growth, causes apoptosis of Glioma cells
      and inhibits STAT 3 signaling. In addition, it might also be useful for the
      treatment of individuals with glioma. 

PMID- 24945374
TI  - The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for
      Head and Neck Cancers.
AB  - The Jacobian of the deformation field of the registration between images taken
      during Radiotherapy is a measure of compression/expansion of the voxels within an
      organ. The Jacobian mean value was applied to investigate possible correlations
      between parotid deformation and anatomical, clinical and dosimetric parameters.
      Data of 84 patients were analyzed. Parotid deformation was evaluated through
      Jacobian maps of images taken at the start and at the end of the treatment.
      Several clinical, geometrical and dosimetric factors were considered. Correlation
      between Jacobian mean value and these parameters was assessed through Spearman's
      test. Univariate and multivariate logistic analyses were performed by considering
      as the end point the first quartile value of the Jacobian mean value. Parotid
      dose volume histograms were stratified according to gland deformation, assessing
      the most predictive dose-volume combination. At multivariate analysis, age (p =
      0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the
      parotid volume receiving more than 10 Gy (p = 0.02) were found as the best
      independent predictors, by considering Jacobian mean value <first quartile as the
      end point. By comparing the average dose volume histogram of parotids with
      Jacobian mean value <first quartile and >fist quartile, the parotid volume
      receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric
      parameters. Parotid glands were divided in three different sub-groups (bad-,
      medium- and good dose volume histogram). The risk to have Jacobian means value
      lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three
      groups. By including in the multivariate analysis this "dose volume grouping"
      parameter, age and bad dose volume histogram were found as the most predictive
      parameters for large shrinkage. The pattern of parotid deformation may be well
      predicted by some pre-treatment variables; a bad dose volume histogram seems the
      most important predictor. 

PMID- 24945375
TI  - Helical and Static-port Tomotherapy Using the Newly-developed Dynamic Jaws
      Technology for Lung Cancer.
AB  - With the newly developed dynamic jaws technology, radiation dose for the cranio
      caudal edges of a target can be lowered in the treatment with tomotherapy. We
      compared dynamic-jaw- and fixed-jaw-mode plans for lung cancer. In 35 patients,
      four plans using the 2.5-cm dynamic-, 2.5-cm fixed-, 5.0-cm dynamic-, and 5.0-cm
      fixed-jaw modes were generated. For 10 patients with upper lobe stage I lung
      cancer, the helical tomotherapy mode was used. Fifty-six Gy in 8 fractions was
      prescribed as a minimum coverage dose for 95% of the target (D95%). For 25
      patients with locally advanced lung cancer, plans using four static ports
      (TomoDirect(r) mode) were made. Sixty Gy in 30 daily fractions for the primary
      tumor and swollen lymph nodes and 51 Gy in 30 fractions for prophylactic lymph
      node areas were prescribed as median doses. The mean conformity index of the
      planning target volume were similar among the four plans. The mean V5 Gy of the
      lung for 2.5-cm dynamic-, 2.5-cm fixed-, 5.0-cm dynamic-, and 5.0-cm fixed-jaw
      mode plans were 18.5%, 21.8%, 20.1%, and 29.4%, respectively (p < 0.0001), for
      patients with stage I lung cancer, and 37.3%, 38.7%, 40.4%, and 44.0%,
      respectively (p < 0.0001), for patients with locally advanced lung cancer. The
      mean V5 Gy of the whole body was 1,826, 2,143, 1,983, and 2,939 ml, respectively
      (p < 0.0001), for patients with stage I lung cancer and 4,849, 5,197, 5,220, and
      6,154 ml, respectively (p < 0.0001), for patients with locally advanced lung
      cancer. Treatment time was reduced by 21-39% in 5.0-cm dynamic-jaw plans compared
      to 2.5-cm plans. Regarding dose distribution, 2.5-cm dynamic-jaw plans were the
      best, and 5.0-cm dynamic-jaw plans were comparable to 2.5-cm fixed-jaw plans with
      shorter treatment times. The dynamic-jaw mode should be used instead of the
      conventional fixed-jaw mode in tomotherapy for lung cancer. 

PMID- 24945376
TI  - Pharmacotherapy in refractory anaphylaxis: when intramuscular epinephrine fails.
AB  - PURPOSE OF REVIEW: This review aims to provide an evidence-based overview of
      several pharmacotherapeutic options available for refractory anaphylaxis when
      intramuscular epinephrine, the drug of choice, fails to provide resolution of
      signs and symptoms. RECENT FINDINGS: The evidence base for the therapy of
      anaphylaxis is comparatively weak and is largely based on consensus expert
      recommendations and case reports. There is an increasing recognition that this is
      problematic. The level of evidence for epinephrine use in anaphylaxis is higher
      than for other agents. Recent systematic reviews have confirmed the lack of high
      grade evidence to support use of antihistamines and corticosteroids in
      anaphylaxis, both of which statistically continue to be used more frequently than
      epinephrine. Newer pharmacotherapeutic agents have been proffered, but none has
      been evaluated with scientific rigor. SUMMARY: Some anaphylactic reactions are so
      severe that treatment is unsuccessful despite rapid recognition and treatment.
      Improving the evidence base for the various treatment modalities may further help
      minimize fatalities once anaphylaxis is recognized. Consensus expert
      recommendations and case reports suggest a number of pharmacotherapeutic agents
      that are worthy of high-quality scrutiny through randomized controlled studies in
      which both treatment and placebo arms receive intramuscular epinephrine
      injections.

PMID- 24945377
TI  - Vaccine safety and efficacy evaluation of a recombinant bovine respiratory
      syncytial virus (BRSV) with deletion of the SH gene and subunit vaccines based on
      recombinant human RSV proteins: N-nanorings, P and M2-1, in calves with maternal
      antibodies.
AB  - The development of safe and effective vaccines against both bovine and human
      respiratory syncytial viruses (BRSV, HRSV) to be used in the presence of RSV
      specific maternally-derived antibodies (MDA) remains a high priority in human and
      veterinary medicine. Herein, we present safety and efficacy results from a
      virulent BRSV challenge of calves with MDA, which were immunized with one of
      three vaccine candidates that allow serological differentiation of infected from
      vaccinated animals (DIVA): an SH gene-deleted recombinant BRSV (DeltaSHrBRSV),
      and two subunit (SU) formulations based on HRSV-P, -M2-1, and -N recombinant
      proteins displaying BRSV-F and -G epitopes, adjuvanted by either oil emulsion
      (Montanide ISA71VG, SUMont) or immunostimulating complex matrices (AbISCO-300,
      SUAbis). Whereas all control animals developed severe respiratory disease and
      shed high levels of virus following BRSV challenge, DeltaSHrBRSV-immunized calves
      demonstrated almost complete clinical and virological protection five weeks after
      a single intranasal vaccination. Although mucosal vaccination with DeltaSHrBRSV
      failed to induce a detectable immunological response, there was a rapid and
      strong anamnestic mucosal BRSV-specific IgA, virus neutralizing antibody and
      local T cell response following challenge with virulent BRSV. Calves immunized
      twice intramuscularly, three weeks apart with SUMont were also well protected two
      weeks after boost. The protection was not as pronounced as that in DeltaSHrBRSV
      immunized animals, but superior to those immunized twice subcutaneously three
      weeks apart with SUAbis. Antibody responses induced by the subunit vaccines were
      non-neutralizing and not directed against BRSV F or G proteins. When formulated
      as SUMont but not as SUAbis, the HRSV N, P and M2-1 proteins induced strong
      systemic cross-protective cell-mediated immune responses detectable already after
      priming. DeltaSHrBRSV and SUMont are two promising DIVA-compatible vaccines,
      apparently inducing protection by different immune responses that were influenced
      by vaccine-composition, immunization route and regimen. 

PMID- 24945378
TI  - An invertebrate Warburg effect: a shrimp virus achieves successful replication by
      altering the host metabolome via the PI3K-Akt-mTOR pathway.
AB  - In this study, we used a systems biology approach to investigate changes in the
      proteome and metabolome of shrimp hemocytes infected by the invertebrate virus
      WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi)
      and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, there was significant
      up-regulation of the markers of several metabolic pathways associated with the
      vertebrate Warburg effect (or aerobic glycolysis), including glycolysis, the
      pentose phosphate pathway, nucleotide biosynthesis, glutaminolysis and amino acid
      biosynthesis. We show that the PI3K-Akt-mTOR pathway was of central importance in
      triggering this WSSV-induced Warburg effect. Although dsRNA silencing of the
      mTORC1 activator Rheb had only a relatively minor impact on WSSV replication, in
      vivo chemical inhibition of Akt, mTORC1 and mTORC2 suppressed the WSSV-induced
      Warburg effect and reduced both WSSV gene expression and viral genome
      replication. When the Warburg effect was suppressed by pretreatment with the mTOR
      inhibitor Torin 1, even the subsequent up-regulation of the TCA cycle was
      insufficient to satisfy the virus's requirements for energy and macromolecular
      precursors. The WSSV-induced Warburg effect therefore appears to be essential for
      successful viral replication. 

PMID- 24945379
TI  - Epidermal growth factor-like domain-containing protein 7 (EGFL7) enhances EGF
      receptor-AKT signaling, epithelial-mesenchymal transition, and metastasis of
      gastric cancer cells.
AB  - Epidermal growth factor-like domain-containing protein 7 (EGFL7) is upregulated
      in human epithelial tumors and so is a potential biomarker for malignancy.
      Indeed, previous studies have shown that high EGFL7 expression promotes
      infiltration and metastasis of gastric carcinoma. The epithelial-mesenchymal
      transition (EMT) initiates the metastatic cascade and endows cancer cells with
      invasive and migratory capacity; however, it is not known if EGFL7 promotes
      metastasis by triggering EMT. We found that EGFL7 was overexpressed in multiple
      human gastric cancer (GC) cell lines and that overexpression promoted cell
      invasion and migration as revealed by scratch wound and transwell migration
      assays. Conversely, shRNA-mediated EGFL7 knockdown reduced invasion and
      migration. Furthermore, EGFL7-overexpressing cells grew into larger tumors and
      were more likely to metastasize to the liver compared to underexpressing CG cells
      following subcutaneous injection in mice. EGFL7 overexpression protected GC cell
      lines against anoikis, providing a plausible mechanism for this enhanced
      metastatic capacity. In excised human gastric tumors, expression of EGFL7 was
      positively correlated with expression levels of the mesenchymal marker vimentin
      and the EMT-associated transcription repressor Snail, and negatively correlated
      with expression of the epithelial cell marker E-cadherin. In GC cell lines, EGFL7
      knockdown reversed morphological signs of EMT and decreased both vimentin and
      Snail expression. In addition, EGFL7 overexpression promoted EGF receptor (EGFR)
      and protein kinase B (AKT) phospho-activation, effects markedly suppressed by the
      EGFR tyrosine kinase inhibitor AG1478. Moreover, AG1478 also reduced the elevated
      invasive and migratory capacity of GC cell lines overexpressing EGFL7.
      Collectively, these results strongly suggest that EGFL7 promotes metastasis by
      activating EMT through an EGFR-AKT-Snail signaling pathway. Disruption of EGFL7
      EGFR-AKT-Snail signaling may a promising therapeutic strategy for gastric cancer.

PMID- 24945380
TI  - Transarterial chemoembolization (TACE) plus sorafenib versus TACE for
      intermediate or advanced stage hepatocellular carcinoma: a meta-analysis.
AB  - BACKGROUND: Sorafenib is used in patients with intermediate or advanced stage
      hepatocellular carcinoma (HCC) before or after of transarterial chemoembolization
      (TACE). However, the survival outcomes of TACE combined with sorafenib versus
      TACE alone remain controversial. Thus, we conducted a meta-analysis to evaluate
      the efficacy and safety of the combination therapy of TACE plus sorafenib in
      patients with intermediate or advanced stage of HCC. METHODS: Pubmed and Embase
      databases were systematically reviewed for studies published up to November 2013,
      that compared TACE alone or in combination with sorafenib. Pooled hazard ratios
      (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival
      (OS), time to progression (TTP), objective response rate (ORR), and progression
      free survival (PFS) using random-effects or fixed-effects model, depending on the
      heterogeneity between the included studies. RESULTS: Six studies published from
      2011 to 2013, with a total of 1254 patients, were included in this meta-analysis.
      The pooled results showed that TACE combined with sorafenib significantly
      improved OS (HR = 0.65; 95% CI: 0.47-0.89, P = 0.007), TTP (HR = 0.68; 95% CI:
      0.52-0.87, P = 0.003), ORR (HR = 1.06; 95% CI: 1.01-1.12, P = 0.021), but did not
      affect PFS (HR = 0.84; 95% CI: 0.62-1.14, P = 0.267). The incidence of grade
      III/IV adverse reaction was higher in the TACE plus sorafenib group than in the
      TACE group. CONCLUSIONS: The meta-analysis confirmed that the combination therapy
      of TACE plus sorafenib in patients with intermediate or advanced stage of HCC,
      can improve the OS, TTP, and ORR. This combination therapy was also associated
      with a significantly increased risk of adverse reactions.

PMID- 24945381
TI  - Cost-effective use of silver dressings for the treatment of hard-to-heal chronic
      venous leg ulcers.
AB  - AIM: To estimate the cost-effectiveness of silver dressings using a health
      economic model based on time-to-wound-healing in hard-to-heal chronic venous leg
      ulcers (VLUs). BACKGROUND: Chronic venous ulceration affects 1-3% of the adult
      population and typically has a protracted course of healing, resulting in
      considerable costs to the healthcare system. The pathogenesis of VLUs includes
      excessive and prolonged inflammation which is often related to critical
      colonisation and early infection. The use of silver dressings to control this
      bioburden and improve wound healing rates remains controversial. METHODS: A
      decision tree was constructed to evaluate the cost-effectiveness of treatment
      with silver compared with non-silver dressings for four weeks in a primary care
      setting. The outcomes: 'Healed ulcer', 'Healing ulcer' or 'No improvement' were
      developed, reflecting the relative reduction in ulcer area from baseline to four
      weeks of treatment. A data set from a recent meta-analysis, based on four RCTs,
      was applied to the model. RESULTS: Treatment with silver dressings for an initial
      four weeks was found to give a total cost saving (L141.57) compared with
      treatment with non-silver dressings. In addition, patients treated with silver
      dressings had a faster wound closure compared with those who had been treated
      with non-silver dressings. CONCLUSION: The use of silver dressings improves
      healing time and can lead to overall cost savings. These results can be used to
      guide healthcare decision makers in evaluating the economic aspects of treatment
      with silver dressings in hard-to-heal chronic VLUs.

PMID- 24945382
TI  - Real-time fluorescence assays to monitor duplex unwinding and ATPase activities
      of helicases.
AB  - Many physiological functions of helicases are dependent on their ability to
      unwind nucleic acid duplexes in an ATP-dependent fashion. Determining the kinetic
      frameworks of these processes is crucial to understanding how these proteins
      function. We recently developed a fluorescence assay to monitor RNA duplex
      unwinding by DEAD-box helicases in real time. In this assay, two fluorescently
      modified short reporter oligonucleotides are annealed to an unmodified RNA
      loading strand of any length so that the fluorescent moieties of the two
      reporters find themselves in close proximity to each other and fluorescence is
      quenched. One reporter is modified with cyanine 3 (Cy3), whereas the other is
      modified with a spectrally paired black-hole quencher (BHQ). As the helicase
      unwinds the loading strand, the enzyme displaces the Cy3-modified reporter, which
      will bind to a capture or competitor DNA strand, permanently separating it from
      the BHQ-modified reporter. Complete separation of the Cy3-modified reporter
      strand is thus detected as an increase in total fluorescence. This assay is
      compatible with reagentless biosensors to monitor ATPase activity so that the
      coupling between ATP hydrolysis and duplex unwinding can be determined. With the
      protocol described, obtaining data and analyzing results of unwinding and ATPase
      assays takes ~4 h. 

PMID- 24945383
TI  - Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells
      from the adult mouse and rat heart.
AB  - This protocol describes the isolation of endogenous c-Kit (also known as CD117)
      positive (c-Kit(+)), CD45-negative (CD45(-)) cardiac stem cells (eCSCs) from
      whole adult mouse and rat hearts. The heart is enzymatically digested via
      retrograde perfusion of the coronary circulation, resulting in rapid and
      extensive breakdown of the whole heart. Next, the tissue is mechanically
      dissociated further and cell fractions are separated by centrifugation. The c
      Kit(+)CD45(-) eCSC population is isolated by magnetic-activated cell sorting
      technology and purity and cell numbers are assessed by flow cytometry. This
      process takes ~4 h for mouse eCSCs or 4.5 h for rat eCSCs. We also describe how
      to characterize c-Kit(+)CD45(-) eCSCs. The c-Kit(+)CD45(-) eCSCs exhibit the
      defining characteristics of stem cells: they are self-renewing, clonogenic and
      multipotent. This protocol also describes how to differentiate eCSCs into three
      main cardiac lineages: functional, beating cardiomyocytes, smooth muscle, and
      endothelial cells. These processes take 17-20 d. 

PMID- 24945384
TI  - Advanced CLARITY for rapid and high-resolution imaging of intact tissues.
AB  - CLARITY is a method for chemical transformation of intact biological tissues into
      a hydrogel-tissue hybrid, which becomes amenable to interrogation with light and
      macromolecular labels while retaining fine structure and native biological
      molecules. This emerging accessibility of information from large intact samples
      has created both new opportunities and new challenges. Here we describe protocols
      spanning multiple dimensions of the CLARITY workflow, ranging from simple,
      reliable and efficient lipid removal without electrophoretic instrumentation
      (passive CLARITY) to optimized objectives and integration with light-sheet optics
      (CLARITY-optimized light-sheet microscopy (COLM)) for accelerating data
      collection from clarified samples by several orders of magnitude while
      maintaining or increasing quality and resolution. The entire protocol takes from
      7-28 d to complete for an adult mouse brain, including hydrogel embedding, full
      lipid removal, whole-brain antibody staining (which, if needed, accounts for 7-10
      of the days), and whole-brain high-resolution imaging; timing within this window
      depends on the choice of lipid removal options, on the size of the tissue, and on
      the number and type of immunostaining rounds performed. This protocol has been
      successfully applied to the study of adult mouse, adult zebrafish and adult human
      brains, and it may find many other applications in the structural and molecular
      analysis of large assembled biological systems. 

PMID- 24945386
TI  - Distal tibial fractures and pilon fractures.
AB  - Fractures of the distal tibia are often very severe injuries that generally occur
      in the context of high-energy trauma and present with significant concomitant
      soft tissue involvement. Open fractures and extensive destruction of the
      articular surfaces are important challenges to the treating surgeon. In
      consequence the outcome for distal meta- and epiphyseal tibial fractures depends
      largely on the severity of the soft tissue injury and its management.
      Conventionally, tibial pilon fractures require surgical intervention.
      Conservative treatment would only be considered in some exceptional cases, for
      example, inoperability of the patient. Controversial discussion of optimal
      surgical technique and optimal timing of surgery is ongoing. There is broad
      consensus that soft tissue consolidation must have first priority as this is the
      basis for both fracture healing and good long-term outcomes. Surgical
      intervention can be managed as a one-stage or multi-stage procedure to achieve
      internal or external fracture fixation. 

PMID- 24945385
TI  - Efficient PhiC31 integrase-mediated site-specific germline transformation of
      Anopheles gambiae.
AB  - Current transgenic methodology developed for mosquitoes has not been applied
      widely to the major malaria vector Anopheles gambiae, which has proved more
      difficult to genetically manipulate than other mosquito species and dipteran
      insects. In this protocol, we describe PhiC31-mediated site-specific integration
      of transgenes into the genome of A. gambiae. The PhiC31 system has many
      advantages over 'classical' transposon-mediated germline transformation systems,
      because it allows integration of large transgenes at specific, characterized
      genomic locations. Starting from a general protocol, we have optimized steps from
      embryo collection to co-injection of transgene-containing plasmid and in vitro
      produced PhiC31 integrase mRNA. We also provide tips for screening transgenic
      larvae. The outlined procedure provides robust transformation in A. gambiae,
      resulting in homozygous transgenic lines in ~2-3 months. 

PMID- 24945387
TI  - Fractures of the calcaneus: current treatment strategies.
AB  - Displaced, intra-articular fractures of the calcaneus represent a surgical
      challenge and the ideal choice of treatment remains a subject of continued
      debate. Open reduction and stable internal fixation without joint transfixation
      has been established as the standard treatment for most of these fractures with
      good to excellent results in more than two thirds of patients in larger clinical
      series. The extended lateral approach respects the neurovascular supply to the
      heel and allows a good exposition of the fractured lateral wall, the subtalar and
      calcaneocuboid joints, but wound healing problems cannot be completely avoided
      despite meticulous soft tissue handling. Percuatneous and less invasive
      procedures have successfully lowered the rates of wound complications but exact
      anatomic reduction remains an important issue. Care must be taken not to overlook
      atypical fractures like sustentacular fractures and fracture-dislocations of the
      calcaneus that are treated with a small medial or curved epimalleolar lateral
      approach, respectively. The use of bone grafting or bone substitutes for defect
      filling appears not necessary in most cases. Prognostic factors that can be
      influenced by the surgeon are anatomical reduction of the overall shape of the
      calcaneus and congruity of the subtalar joint which should both be controlled
      intraoperatively. Treatment results are adversely affected by severity of injury,
      open fractures, bilateral fractures, a high body mass index and smoking. Early,
      stable soft tissue coverage with pedicled or free flaps appears to lower
      infection rates and improve the functional results after open fractures.
      Calcaneal malunions and nonunions are disabling conditions resulting from either
      non-operative treatment or inadequate reduction and fixation of displaced
      fractures. Deformity correction is tailored to the type of deformity and
      individual patient needs. Treatment options include lateral wall decompression,
      in situ- or corrective subtalar arthrodesis and calcaneal osteotomies accompanied
      by soft tissue-balancing.

PMID- 24945388
TI  - Colles' fractures: functional treatment in supination.
AB  - PURPOSE OF THE STUDY: Abraham Colles classified and described fractures of the
      distal epiphyseal radius. He recommended the arm should be immobilized in a cast
      that extends from the base of the fingers to above the elbow, while holding this
      joint at ninety degrees of flexion the forearm in pronation and the wrist in
      slight flexion and ulnar deviation. We identified the brachioradialis muscle as
      the main culprit in the frequently observed loss of reduction of the fracture.
      Since the brachioradialis is attached to the distal region of the radius and
      functions as a flexor of the elbow when the forearm is in pronation, its
      stimulation easily displaces a reduced fracture, particularly if its geometry
      suggests axial instability. We concluded that post-reduction stabilization in
      supination was more desirable than in pronation. MATERIAL AND METHODS:
      Prospective study of one hundred and fifty-six patients suffering from Colles'
      fractures who were treated with the functional method. Approximately one-half of
      the fractures were immobilized in pronation and the other half in supination. The
      median age of the patients was 49 years. After approximately eleven days of
      immobilization in an above-the-elbow cast that held the forearm in a relaxed
      attitude of supination and the wrist in slight flexion and ulnar deviation, a new
      cast or brace was applied. The appliance permitted flexion of the elbow and
      slightly limited extension. We utilized modified Lindstom criteria to assess
      radiological results, according to types of fractures and by groups treated in
      supination and pronation. RESULTS: In the type I and III (non-displaced) fracture
      series there appeared to be no significant difference in the functional results
      between the pronation and supination treated groups. In the type II category, in
      the supinated fractures, there were 9 excellent, 4 good and no fair or poor
      results. In the pronated group 9 excellent, 8 good and one fair result. The
      functional results in type IV fractures treated in supination were excellent in
      11 instances, good in 7 and fair in 2. In fractures treated in pronation there
      were 5 excellent, 10 good and 5 fair results. There were no poor results in
      either group. 85% of type II fractures and 85% of type IV fractures treated in
      supination had excellent or good results. In the pronation group, 67% had
      excellent or good results in type II and 40% in type IV classification. In
      combining the results for all types of braced Colles' fractures, (I-IV) 93% of
      the supination group and 87% of the pronation group achieved excellent or good
      functional results. In analyzing overall results regardless of type of fracture
      or position of immobilization, 90% of the patients had excellent or good results.
      CONCLUSION: We treated Colles' fractures in supination and compared the results
      with those obtained when treated in pronation. The results indicated a lower
      incidence of re-displacement in the supination group. We developed a forearm
      brace that permits flexion of the elbow, but prevented pronation of the forearm,
      and limited extension of the elbow in approximately the last fifteen degrees. It
      permits minimally limited flexion of the wrist but prevents wrist dorsiflexion.
      It makes impossible any radial deviation. The place of surgery in the management
      of Colles' fractures should be limited to those fractures that when treated by
      non-surgical means are not likely to render satisfactory functional and cosmetic
      results. There is not at this time a consensus as to when to use the surgical
      approach. The complication rate from the surgery have not clearly identify
      superiority of one over the other. Nonetheless, the surgical treatment has a
      definite place in the armamentarium of the orthopaedic surgeon. In a number of
      situations, it is the treatment of choice.

PMID- 24945389
TI  - [Axial lumbar interbody fusion: prospective monocentric study].
AB  - PURPOSE OF THE STUDY: The aim of this prospective study was to evaluate clinical
      and radiographic results in the patients who underwent L5-S1 fixation using the
      technique of percutaneous lumbar interbody fusion (AxiaLIF). MATERIAL: The study
      comprised 23 patients, 11 women and 12 men, who ranged from age of 21 to 63
      years, with an average of 48.2 years. In all patients surgical posterior
      stabilisation involving the L5-S1 segment had previously been done. The initial
      indications for surgery were L5-S1 spondylolisthesis in 20 and L5-S1 spondylosis
      and stenosis in three patients. METHODS: The AxiaLIF technique for L5-S1 fixation
      was indicated in overweight patients and in those after repeated abdominal or
      retroperitoneal surgery. A suitable position and shape of the sacrum or
      lumbosacral junction was another criterion. The patients were evaluated between
      26 and 56 months (average, 40.4 months) after primary surgery and, on the basis
      of CT and radiographic findings, bone union and lumbosacral junction stability
      were assessed. The clinical outcome was investigated using the ODI and VAS
      systems and the results were statistically analysed by the Wilcoxon test for
      paired samples with statistical significance set at a level of 0.05. RESULTS: The
      average VAS value was 6.6 before surgery and, after surgery, 5.2 at three months,
      4.2 at six months, 3.1 at one year, 2.9 at two years and 2.1 at three years
      (n=18). At two post-operative years, improvement in the VAS value by 56.1% was
      recorded. The average pre-operative ODI value was 25.1; the post-operative values
      were 17.0 at six months, 12.3 at one year, 10.6 at two years and 8.2 at three
      years (n=18). At two years after surgery the ODI value improved by 57.8%. To the
      question concerning their willingness to undergo, with acquired experience,
      surgery for the same diagnosis, 21 patients (91.3%) gave an affirmative answer.
      Neither screw breakage nor neurovascular damage or rectal injury was found. CT
      scans showed complete interbody bone fusion in 22 of the 23 patients (95.6%), In
      one patient the finding was not clear. Also, posterolateral fusion was achieved
      in all but one patients (95.6%). A stable L5-S1 segment was found in all patients
      at all follow-up intervals. The improvement in both VAS and ODI values was
      statistically significant. DISCUSSION: In addition to indications usual in
      degenerative disc disease, overweight patients, those who had repeated trans- or
      retroperitoneal surgery in the L5-S1 region or who underwent long posterior
      fixation to stabilise the caudal margin of instrumentation are indicated for the
      AxiaLIF procedure. The clinical results of our study are in agreement with the
      conclusions of other studies and are similar to the outcomes of surgery using
      other types of fusion or dynamic stabilisation for this diagnosis. The high rate
      of fusion in our group is affected by use of a rigid transpedicular fixator
      together with posterolateral arthrodesis. On the other hand, no negative effects
      of only synthetic bone applied to interbody space were recorded. CONCLUSIONS: The
      percutaneous axial pre-sacral approach to the L5-S1 interbody space with
      application of a double-treaded screw is another option for the management of
      this much strained segment. The technique is useful particularly when
      contraindications for conventional surgical procedures are present in patients
      with anatomical anomalies, in overweight patients or in those who have had
      repeated surgery in the region. Clinical outcomes and the success rate for L5-S1
      bone fusion are comparable with conventional techniques. Complications are rare
      but their treatment is difficult.

PMID- 24945391
TI  - Is attention deficit and hyperactivity disorder a risk factor for sustaining
      fractures of proximal humerus?
AB  - PURPOSE OF THE STUDY: To evaluate whether or not children with displaced proximal
      humerus fractures are more likely to have attention deficit and hyperactivity
      disorder (ADHD). PATIENTS AND METHOD: Between January 2010 and February 2013, we
      retrospectively evaluated 42 children with proximal humerus fractures.
      Requirements for inclusion were an open epiphyseal plate and a non-pathological
      fracture of the proximal humerus. Fractures were classified according to Salter
      Harris, Neer and Horwitz. Following orthopaedic examination, all of the children
      were consulted to child psychiatry department of our hospital. Orthopaedic
      examination included a detailed physical examination; the assessment of the
      overall shoulder functions using the Constant score. Diagnostic and Statistical
      Manual of Mental Disorders, Text Revisions (DSM-IV-TR) were used for psychiatric
      examination. RESULTS: 9 of the 42 children with proximal humerus fractures
      consulted to child psychiatry were put ADHD diagnoses (21 %). Of the remaining 33
      children without ADHD diagnosis, 5 children were operated; percentage of surgery
      was 15%. We found statistically significant difference between the rates of ADHD
      diagnosed children with proximal humerus fractures and ADHD diagnoses in normal
      population (p<0.01). There was also statistically significant difference between
      operation rates of children with or without ADHD diagnosis (55 % vs. 15 %)
      (p<0,01). CONCLUSIONS: ADHD can be accepted as a risk factor for sustaining high
      energy trauma and rate of ADHD children who were operated was significantly more
      than normal children. This might be due to more displaced, open fractures or
      polytrauma - higher energy trauma- they sustained. Deciding on the treatment
      method, surgery may be treatment of choice in certain children with severely
      displaced, irreducable, fractures or polytrauma with accompanying ADHD due to the
      potential difficulties during follow up period.

PMID- 24945390
TI  - [Fixation of acetabular fractures. a novel method of pre-operative Omega plate
      contouring].
AB  - PURPOSE OF THE STUDY: The aim of the study was to describe a novel Omega plate
      and the procedure for obtaining an accurate pelvic inlet view, the mode of pre
      operative plate contouring, the surgical procedure used and the evaluation of
      results in the first 15 patients treated using this method. MATERIAL AND METHODS:
      In the period 2009-2011, a total of 232 patients underwent osteosynthesis for
      pelvic fractures. Out of them, 52 were treated by the modified Stoppa approach
      and 12 with the original Omega plate. Between July 2010 and January 2014, a novel
      3.5-mm Omega plate was used in 12 men and 3 women. The average duration of follow
      up was 8.5 months in 11 patients; four were shortly after surgery. The multi
      functional Omega plate is described in detail. An exact pelvic inlet projection,
      named the "computer tomography-defined (CTD) view", was based on pre-operative CT
      examination. It facilitates pre-operative contouring of the plate according to a
      mirror image of the uninjured half of the pelvis. The surgical procedure enables
      us to apply the contoured plate to the correct position; the plate completes
      reduction, restores normal pelvic anatomy and makes operative time shorter. The
      radiographic evaluation of post-operative results was done using the Matta
      classification and functional outcome was assessed by the Harris Hip Score.
      RESULTS: Surgery using the isolated Stoppa approach was carried out in 11
      patients and a procedure combining the Stoppa approach with another method was
      used in four patients. All operations were successfully completed, during two of
      them the external iliac vein was injured and treated by vascular suturing. No
      other vascular or nerve injury occurred. One deep wound infection successfully
      healed was recorded. The post-operative radiographic results were excellent or
      satisfactory in 12 and poor in three patients. At follow-ups of 6 to 12 months,
      no failure of fracture reduction or osteosynthesis was recorded in 11 patients.
      Neither avascular necrosis of the femoral head nor heterotopic ossification was
      found. One patient showed signs of post-injury arthritis at 6 months after
      surgery. The functional result assessed by the Harris Hip Score was excellent in
      seven patients, good in two (one of them with gonarthrosis), satisfactory in one
      patient with contralateral total hip replacement and ipsilateral gonarthrosis,
      and poor in one patient with hemiparesis after a stroke. DISCUSSION: Shape and
      size variability in CTD pelvic inlet views do not allow us to create a unified
      anatomically correct implant. Contouring during the operative procedure may not
      be accurate enough and significantly prolongs the time of surgery. Therefore, a
      custom-made plate for each patient seems to be an optimal method. It has been
      demonstrated on a group of 50 patients that CTD images of the right and left
      halves of the pelvis are identical in 68% and very similar (variation in length
      up to 5 mm and in curvature up to 3 mm) in 18%. At present plate contouring
      according to a mirror image of the acetabulum, which will be obtained by 3D
      printing, is prepared. CONCLUSIONS: Pre-operative contouring of an Omega plate
      based on a post-injury CT scan of the uninjured half of the pelvis is over 80%
      accurate or almost accurate. The multi-functional 3.5-mm pelvic plate Omega
      allows us to stabilise complicated fractures of the superior ramus of the pubic
      bone, anterior acetabular column or quadrilateral plate as well as fractures
      above the linea arcuata or uncomplicated fractures of the posterior column. The
      stabilisation of all fragments of the anterior column and quadrilateral plate is
      very firm and the Omega plate is resistant to fragment redisplacement. Also, it
      is its advantage that it can remain in situ if total hip arthroplasty is required
      later.

PMID- 24945392
TI  - [Tangent sign - a reliable predictor of risk for tendon re-rupture in rotator
      cuff repair].
AB  - PURPOSE OF THE STUDY: Repair techniques for rotator cuff injury are currently
      well advanced. However, the risk of re-rupture, particularly when severe damage
      to the tendons has been repaired, is still high. The causes of failure can be due
      to the extent of injury, a repair done on a highly degenerated tendon with
      diminished viability or ischaemic damage to the tendon tissue resulting from
      suture material. The aim of the study was to ascertain the reliability of the
      tangent sign, a commonly used indicator of the degree of suprasupinatus muscle
      atrophy, in the prediction of risk for tendon re-rupture in the post-operative
      period. MATERIAL AND METHODS: In 2011 the rotator cuff torn tendons were repaired
      by the method of double-row suture in 37 patients. The surgery was done by an
      open technique using the deltoid-splitting approach. A pre-operative magnetic
      resonance image (MRI) of the shoulder was obtained in all patients and each was
      assessed by a competent independent radiology specialist with a focus on the
      extent of a tendon lesion and the tangent sign. At 2-year follow-up, the results
      of repeated MRI were evaluated in view of the state of repaired tendons and, if a
      re-tear was found, its relation to the original suture and its extent in the
      sagittal plane were determined. The pre- and post-operative MRI findings were
      compared to find out how the presence or absence of a tangent sign before surgery
      relates to the incidence of supraspinatus tendon re-rupture at 2 years after
      surgery. The results were statistically analysed using Student's t-test and the
      Chi-square test. RESULTS: Of the 37 shoulders, in the pre-operative period, a
      tangent sign was identified in 21 (56.8%). The average size of a rotator cuff
      tear was 29.3 mm for the whole group. For the shoulders with no tangent sign, the
      average value was 21.8 mm, for those with a tangent sign present, it was 39.6 mm.
      At 2-year follow-up, no tear was found in the patients in whom preoperative MRI
      showed no tangent sign while re-tears were recorded in 18 of 21 shoulders (85.7%)
      with a tangent sign present before surgery. On the average, the re-rupture had
      40.8 mm in size and, in all cases, it occurred at the site of tendon re-insertion
      into the greater tubercle. These results were statistically significant (p <
      0.01). DISCUSSION: In repair of injury to the tendons of the rotator cuff
      muscles, emphasis is currently placed on a thorough pre-operative examination.
      MRI is an important part of the diagnostic procedure because it provides a
      detailed image of the muscle as a whole. Although great advances have recently
      been made in both the diagnostic and surgical techniques, the incidence of tendon
      re-rupture within a few years of the procedure is still high. CONCLUSION: Our
      results show that the presence of a tangent sign detected by pre-operative MRI
      examination of the shoulder can be an important predictor of failure in rotator
      cuff repair and can also turn attention to the selection of an alternative
      technique to be used.

PMID- 24945393
TI  - [Metal staples versus conventional suture for wound closure in total knee
      arthroplasty].
AB  - PURPOSE OF THE STUDY: Surgical incision closure, as well as total joint
      replacement itself, plays a key role in the overall outcome of an arthroplasty
      procedure. Uncomplicated wound healing is the essential condition of successful
      rehabilitation and the patient's return to normal activities. Although there are
      many innovative suturing techniques which offer advantages, their safety is still
      being discussed. The aim of this prospective non-blind randomised study was to
      evaluate wound healing and complications in relation to skin incision closure
      with either conventional suture or metal staples. MATERIAL AND METHODS: A total
      of 72 patients, 21 men and 51 women, who underwent a standard primary total knee
      arthroplasty (TKA) at our department in the period from January till June 2013,
      were evaluated. They were allocated to two groups by random assignment based on
      the patient's date of birth (even or odd day of birth). In group 1 (n=39) skin
      was closed using metal staples (Leukosan Skin Stapler), in group 2 (n=33),
      conventional continuous Donati suture was used. The groups, previously assessed
      as independent and comparable in terms of age, gender and BMI, were compared in
      the following criteria: suturing time, duration of wound drainage, wound healing,
      complications, resuturing when necessary, and their relation to the body mass
      index, skin plica thickness and co-morbidities potentially complicating soft
      tissue healing. The differences were statistically evaluated by parametric and
      non-parametric tests, i.e., the median test, chi(2)-test, Student's t-test,
      Fisher's exact test and Pearson's correlation coefficient. The statistical
      significance of differences was set at a level of 0.05. RESULTS: A significant
      difference (p<0.005) between the groups was found in suturing time; the median
      time for staples was 81 sec in comparison with 290 sec for conventional suture.
      In both groups, staples or sutures were removed on the 12 th postoperative day
      and there was no difference in wound drainage (median time, 5 days; p=0.891 for
      both). Treatment for late discharge was required in two sutured wounds (6.1%) and
      in three stapled wounds (7.7%). One of the latter was due to early deep wound
      infection, which later resulted in revision TKA. The groups did not differ in the
      values of either BMI or plica thickness (Pearson's r). DISCUSSION: Views on
      alternative suture techniques for skin closure in orthopaedic surgery vary. In
      this study, the use of metal staples or conventional suture is compared between
      two groups of patients undergoing TKA, i.e., the same type of procedure. The
      advantage of staples involves a quick and simple application but, as reported,
      removal may be more painful with staples than with stitches, and much depends on
      the technique of staple application. The continuous suture technique may produce
      skin strangulation at wound margins, which will complicate healing. Staples
      minimise this risk and are therefore commonly used in TKA surgery. However, only
      very few studies comparing these two suture techniques in TKA patients have been
      published. CONCLUSIONS: Correctly performed skin suturing by means of metal
      staples is not associated with a higher complication rate and is therefore a
      simple, rapid, efficient and economical alternative to the conventional suture
      technique.

PMID- 24945394
TI  - [Middle-third clavicle fracture with ipsilateral acromioclavicular dislocation].
AB  - A rare case of a middle-third clavicle fracture concurrent with ipsilateral
      acromioclavicular dislocation in a 46-year-old women who had fallen off her
      bicycle is presented. The clavicular fracture was managed by locking plate
      osteosynthesis. The acromioclavicular joint was stabilised by traction
      osteorrhaphy that was removed at 7 weeks after the procedure. Both the
      radiographic and clinical outcomes were very good. The epidemiology, aetiology,
      diagnosis and therapy of this injury are discussed.

PMID- 24945395
TI  - Secretory vesicles deliver Cdc42p to sites of polarized growth in S. cerevisiae.
AB  - The activation and localization of the Rho-family GTPase Cdc42p at one pole of a
      cell is necessary for maintaining an axis of polarized growth in many animal and
      fungal cells. How the asymmetric distribution of this key regulator of polarized
      morphogenesis is maintained is not fully understood, though divergent models have
      emerged from a congruence of multiple studies, including one that posits a role
      for polarized secretion. Here we show with S. cerevisiae that Cdc42p associates
      with secretory vesicles in vivo. 

PMID- 24945396
TI  - Multiple readout assay for hormonal (androgenic and antiandrogenic) and cytotoxic
      activity of plant and fungal extracts based on differential prostate cancer cell
      line behavior.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer is one of the most diagnosed
      forms of cancer among men in western regions. Many traditional applications or
      phytotherapeutic concepts propose to inhibit the proliferation of prostate cancer
      cells. In order to detect influences of plant or fungal extracts and derived
      fractions on androgen receptor signaling pathways, a differentiating cell
      proliferation assay was established, which enables the simultaneous detection of
      hormonal and cytotoxic effects. MATERIAL AND METHODS: The well characterized
      prostate cancer cell lines LNCaP and PC-3 were used in a multiple readout assay.
      In all, 186 fractions of 23 traditionally used organisms were screened regarding
      their effects on proliferation of the two prostate cancer cell lines. The
      fractions were prepared by accelerated solvent extraction followed by gradient
      extrography. Extracts of the potential hormonally active plants Cibotium
      barometz, Heteropterys chrysophylla, and Sideroxylon obtusifolium (= Bumelia
      sartorum) were phytochemically investigated. RESULTS: Fractions from Cibotium
      barometz, Cortinarius rubellus, Cyrtomium falcatum, Heteropterys chrysophylla,
      Nephrolepis exaltata, Salvia miltiorrhiza, Sideroxylon obtusifolium, Trichilia
      emetica, and Trimeria grandifolia exhibited hormonal influences on prostate
      cancer cells. Cytotoxic activity towards human cell lines was detected for the
      first time for fractions from Aglaia spectabilis (A. gigantea), Nephrolepis
      exaltata and Cortinarius brunneus. CONCLUSIONS: The differential behavior of the
      two prostate cancer cell lines allows the discrimination between potential
      androgenic or antiandrogenic activities and effects on the estrogen or
      glucocorticoid receptor as well as cytotoxic activities. The combined cell lines
      assay can help to assess the biological activities of material used in
      traditional medicine.

PMID- 24945397
TI  - The protective effect of Phoenix dactylifera L. seeds against CCl4-induced
      hepatotoxicity in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Egyptian medicine, Phoenix
      dactylifera L. (date palm) seeds are listed in folk remedies for the management
      of diabetes, liver diseases and gastrointestinal disorders. The present study was
      conducted to investigate the protective effect of Phoenix dactylifera L. seeds
      aqueous suspension against the chemically-induced hepatic injury in rats.
      METHODS: Liver injury was achieved by exposing Wistar rats to CCl4 (10% in olive
      oil; 0.5 mL/rat; IP) twice a week for 4 weeks. Along with CCl4, aqueous
      suspensions of raw or roasted Phoenix dactylifera seeds (1.0 g/kg) were
      administered orally in a daily manner. RESULTS: Our results demonstrated that
      Phoenix dactylifera seeds significantly improved the CCl4-induced alterations in
      liver function parameters (AST, ALT, ALP and albumin). Moreover, the CCl4-induced
      oxidative stress, represented by elevated thiobarbituric acid reactive substance
      (TBARS), nitric oxide and oxidative DNA damage, was ameliorated by Phoenix
      dactylifera seeds treatment. In addition, Phoenix dactylifera seeds restored the
      activities of hepatic antioxidant enzymes (superoxide dismutase and glutathione S
      transferase) that were declined after CCl4 treatment. Examination of liver
      histopathology revealed that Phoenix dactylifera seeds attenuate the incidence of
      liver lesions (including vacuolization and fibroblast proliferation) triggered by
      CCl4 intoxication. CONCLUSION: The Phoenix dactylifera seeds could be a promising
      candidate for protection against the CCl4-induced liver intoxication, and this
      hepatoprotective effect might be attributed to the antioxidant and free radical
      scavenging activities.

PMID- 24945398
TI  - Topical analgesic, anti-inflammatory and antioxidant properties of Oxybaphus
      nyctagineus: phytochemical characterization of active fractions.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Oxybaphus nyctagineus (Michx.) Sweet has
      traditionally been used by several Native American tribes predominantly as a
      topical anti-inflammatory and analgesic agent. AIM OF THE STUDY: To evaluate the
      antioxidant, analgesic and anti-inflammatory activity of the extracts prepared
      from the aerial parts of Oxybaphus nyctagineus and to characterize the major
      chemical constituents of the bioactive extracts. MATERIALS AND METHODS: Crude
      polar and apolar extracts (PCE and ACE) of the herb of Oxybaphus nyctagineus were
      prepared and tested in the models of the CFA-induced hyperalgesia in rat knee and
      carrageenan-induced paw edema in rat. To identify the active compounds,
      subfractions were prepared by column chromatography and subjected in vitro
      assays, such as antioxidant assays (DPPH, peroxynitrite (ONOO-) scavenging), and
      the LPS-induced IL-1beta release test in human monocytes. Preparative HPLC was
      employed for the isolation of active substances, while phytochemical analysis was
      performed by mean of LC-MS/MS and NMR. RESULTS: The topically administered PCE
      and ACE of Oxybaphus nyctagineus demonstrated a significant analgesic and anti
      inflammatory effect in the inflammation animal models. The subfraction A4 of ACE
      and the subfraction P5 of PCE considerably inhibited the LPS-induced IL-1beta
      release in human monocytes, while the strongest activity was localized in the
      subfraction P5 in the antioxidant assays. The HPLC-MS/MS and NMR analysis
      revealed that 6-methoxyflavonol diglycosides, namely patuletin-3-O-robinobioside
      (1), 6-methoxykaempferol-3-O-robinobioside (2), spinacetin-3-O-robinobioside (3),
      and hydroxy-polyenoic fatty acids, namely corchorifatty acid B (4), 9-hydroxy
      10E,12Z,15Z-octadecatrienoic acid (9-HOT acid) (5), and 9-hydroxy-10E,12Z
      octadecadienoic acid (9-HOD acid) (6) were present in PCE, and in ACE as major
      compounds. CONCLUSION: The results of this study established a pharmacological
      evidence for the traditional use of Oxybaphus nyctagineus as an anti-inflammatory
      agent used topically, and provided data on its phytochemical composition for the
      first time.

PMID- 24945399
TI  - Antiproliferative activity and new argininyl bufadienolide esters from the
      "cururu" toad Rhinella (Bufo) schneideri.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Toads known as "cururu" (Rhinella schneideri)
      have been used in the Brazilian Pantanal and Paraguayan Chaco wetlands to treat
      erysipelas and cancer. The aim of the study was to assess the antiproliferative
      effect of the venom obtained from Rhinella schneideri and to identify its
      constituents by spectroscopic and spectrometric methods. MATERIALS AND METHODS:
      The venom was obtained by gentle pressing the parotid glands of the toads. The
      dry crude drug was analyzed by HPLC-MS-MS and chromatographed on Sephadex LH-20
      to obtain purified compounds and fractions for spectroscopic analysis. The venom
      and fractions were evaluated for antiproliferative activity towards normal human
      lung fibroblasts (MRC-5) and four human cancer cell lines: gastric epithelial
      adenocarcinoma (AGS), lung cancer (SK-MES-1), bladder carcinoma (J82) and
      promyelocytic leukemia (HL-60). RESULTS: From the Rhinella schneideri venom, 29
      compounds were isolated and/or identified by spectroscopic and spectrometric
      means. Three known alkaloids and five argininyl diacids were identified in the
      complex mixture by HPLC-MS-MS. Nine out of fifteen argininyl diacid derivatives
      of the bufadienolides bufalin, marinobufagin and telocinobufagin are reported for
      the first time and four argininyl diacids are described for the first time as
      natural products. The venom and the fractions 9-13 showed a remarkable
      antiproliferative effect, with IC50 values in the range 0.019-0.022, 0.035-0.040,
      0.028-0.064, 0.042-0.056 and 0.044-0.052 ug/mL for MRC-5, AGS, SK-MES-1, J82 and
      HL-60 cell lines, respectively. Under the same experimental conditions, IC50
      values of the reference compound etoposide were 2.296, 0.277, 1.295, 1.884 and
      1.059 ug/mL towards MRC-5, AGS, SK-MES-1, J82 and HL-60 cells, respectively.
      CONCLUSIONS: The venom showed a strong antiproliferative effect towards human
      cancer cells and presented a high chemical diversity in its constituents,
      supporting its use as anticancer agent. These findings encourage further work on
      the chemistry and bioactivity of South American toad venoms.

PMID- 24945400
TI  - Antibacterial activities of extracts from Ugandan medicinal plants used for oral
      care.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are widely used for treatment of
      oral/dental diseases in Uganda. AIM OF THE STUDY: To investigate antibacterial
      activities of 16 commonly used medicinal plants on microorganisms associated with
      periodontal diseases (PD) and dental caries (DC). MATERIALS AND METHODS: Pulp
      juice and solvent extracts (hexane, methanol and water) from the plants were
      tested against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis,
      Tannerella forsythia associated with PD and Streptococcus mutans, Streptococcus
      sobrinus, Lactobacillus acidophilus associated with DC. Tests were done using
      agar well-diffusion (pulp juice) and agar-dilution (Solvent extracts) assays.
      RESULTS: Pulp juice from Zanthoxylum chalybeum and Euclea latidens showed
      activity against all the bacteria, Zanthoxylum chalybeum being most active.
      Hexane extract from aerial part of Helichrysum odoratissimum was most active
      (MIC: 0.125-0.5 mg/ml). Methanol extract from leaves of Lantana trifolia showed
      activity against all bacteria (MIC: 0.25-1 mg/ml). CONCLUSION: Several of the
      tested plants showed antibacterial activities against bacteria associated with PD
      and DC, meriting further investigations.

PMID- 24945402
TI  - Prescription patterns of Chinese herbal products for post-surgery colon cancer
      patients in Taiwan.
AB  - ETHNO-PHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is commonly
      provided to cancer patients, however, the patterns of prescriptions for this type
      of medicine in Taiwan are unclear. This study aimed to evaluate the use of
      traditional Chinese medicine products in colon cancer patients post-surgery in
      Taiwan and to research patterns of TCM. MATERIAL AND METHODS: This was a cross
      sectional study of newly diagnosed colon cancer patients who received surgery
      between 2004 and 2008 identified from the National Health Insurance Research
      Database of Taiwan. The prescription patterns and reasons for the use of TCM for
      colon cancer were analyzed. RESULTS: The results showed that "symptoms, signs and
      ill-defined conditions" (23.3%) and diseases of the digestive system (16.9%) were
      the most common reasons for using Chinese herbal medicine. Xiang-sha-liu-jun-zi
      tang (7.1%), Bu-zhong-yi-qi-tang (4.3%), Jia-wei-xiao-yao-san (4.1%), Shen-Ling
      Bai-Zhu-San (3.7%), Ban-Xia-Xie-Xin-Tang (3.4%), Gui-pi-tang (2.4%), Ping-Wei-San
      (2.4%), Gan-Lu-Yin (2.0%), Bao-He-Wan (1.9%), and Zhen-Ren-Huo-Ming-Yin (1.8%)
      were the most commonly prescribed single Chinese herbal formulae (CHF) for colon
      cancer patients post-surgery. Hedyotis diffusa Willd (Bai Hua She She Cao) (5.1%)
      and Scutellaria barbata (Ban Zhi Lian )(4.8%) were the most commonly prescribed
      single Chinese herbs. CONCLUSIONS: This study identified patterns of TCM use in
      colon cancer patients post-surgery in Taiwan. The herbal ingredients were most
      commonly used for stimulate ghrelin secretion to increase food intake and had
      potential anti-tumor effect. However, further research is required to evaluate
      any beneficial effects which could identify leads for the development of new
      treatment strategies using TCM.

PMID- 24945401
TI  - Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7
      macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Taraxasterol was isolated from the Chinese
      medicinal herb Taraxacum officinale which has been frequently used as a remedy
      for inflammatory diseases. Our previous study has shown that taraxasterol
      inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2
      (PGE2) production in RAW 264.7 macrophages. To elucidate the underlying mechanism
      responsible for these effects, in the present study, we investigated the effects
      of taraxasterol on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2) expression, and mitogen-activated protein kinases (MAPKs) signaling
      pathway in LPS-induced RAW 264.7 macrophages. MATERIALS AND METHODS: RAW 264.7
      cells were pretreated with 2.5, 5 and 12.5 MUg/ml of taraxasterol 1 h prior to
      treatment with 1 MUg/ml of LPS. The mRNA expression levels of iNOS and COX-2 were
      examined by RT-PCR. The protein expression levels of iNOS and COX-2, and the
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c
      Jun N-terminal kinase (JNK) MAPKs were measured by Western blot. RESULTS: The
      mRNA and protein expression levels of iNOS and COX-2 were inhibited by
      taraxasterol in a concentration-dependent manner. Further studies revealed that
      taraxasterol suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW
      264.7 macrophages. CONCLUSIONS: These results indicate that taraxasterol inhibits
      iNOS and COX-2 expression by blocking ERK1/2 and p38 MAPKs signaling pathway.

PMID- 24945406
TI  - Distribution and epidemiological characteristics of published individual patient
      data meta-analyses.
AB  - BACKGROUND: Individual patient data meta-analyses (IPDMAs) prevail as the gold
      standard in clinical evaluations. We investigated the distribution and
      epidemiological characteristics of published IPDMA articles.
      METHODOLOGY/PRINCIPAL FINDINGS: IPDMA articles were identified through
      comprehensive literature searches from PubMed, Embase, and Cochrane library. Two
      investigators independently conducted article identification, data classification
      and extraction. Data related to the article characteristics were collected and
      analyzed descriptively. A total of 829 IPDMA articles indexed until 9 August 2012
      were identified. An average of 3.7 IPDMA articles was published per year.
      Malignant neoplasms (267 [32.2%]) and circulatory diseases (179 [21.6%]) were the
      most frequently occurring topics. On average, each IPDMA article included a
      median of 8 studies (Interquartile range, IQR 5 to 15) involving 2,563 patients
      (IQR 927 to 8,349). Among 829 IPDMA articles, 229 (27.6%) did not perform a
      systematic search to identify related studies. In total, 207 (25.0%) sought and
      included individual patient data (IPD) from the "grey literature". Only 496
      (59.8%) successfully obtained IPD from all identified studies.
      CONCLUSIONS/SIGNIFICANCE: The number of IPDMA articles exhibited an increasing
      trend over the past few years and mainly focused on cancer and circulatory
      diseases. Our data indicated that literature searches, including grey literature
      and data availability were inconsistent among different IPDMA articles. Possible
      biases may arise. Thus, decision makers should not uncritically accept all
      IPDMAs.

PMID- 24945404
TI  - Phenotypic dissection of bone mineral density reveals skeletal site specificity
      and facilitates the identification of novel loci in the genetic regulation of
      bone mass attainment.
AB  - Heritability of bone mineral density (BMD) varies across skeletal sites,
      reflecting different relative contributions of genetic and environmental
      influences. To quantify the degree to which common genetic variants tag and
      environmental factors influence BMD, at different sites, we estimated the genetic
      (rg) and residual (re) correlations between BMD measured at the upper limbs (UL
      BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ~
      4,890 participants recruited by the Avon Longitudinal Study of Parents and their
      Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a
      greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between
      them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43).
      Likewise, the residual correlation between BMD at appendicular sites (r(e) =
      0.55) was higher than the residual correlation between SK-BMD and BMD at
      appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed
      differences in rg and re, genome-wide association meta-analyses were performed (n
      ~ 9,395), combining data from ALSPAC and the Generation R Study identifying 15
      independent signals from 13 loci associated at genome-wide significant level
      across different skeletal regions. Results suggested that previously identified
      BMD-associated variants may exert site-specific effects (i.e. differ in the
      strength of their association and magnitude of effect across different skeletal
      sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and
      UL-BMD when compared to LL-BMD (P = 2.01 * 10(-37)), whilst variants at WNT16
      influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 *
      10(-14)). In addition, we report a novel association between RIN3 (previously
      associated with Paget's disease) and LL-BMD (rs754388: beta = 0.13, SE = 0.02, P
      = 1.4 * 10(-10)). Our results suggest that BMD at different skeletal sites is
      under a mixture of shared and specific genetic and environmental influences.
      Allowing for these differences by performing genome-wide association at different
      skeletal sites may help uncover new genetic influences on BMD.

PMID- 24945405
TI  - The triggering receptor expressed on myeloid cells 2 inhibits complement
      component 1q effector mechanisms and exerts detrimental effects during
      pneumococcal pneumonia.
AB  - Phagocytosis and inflammation within the lungs is crucial for host defense during
      bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was
      proposed to negatively regulate TLR-mediated responses and enhance phagocytosis
      by macrophages, but the role of TREM-2 in respiratory tract infections is
      unknown. Here, we established the presence of TREM-2 on alveolar macrophages (AM)
      and explored the function of TREM-2 in the innate immune response to pneumococcal
      infection in vivo. Unexpectedly, we found Trem-2(-/-) AM to display augmented
      bacterial phagocytosis in vitro and in vivo compared to WT AM. Mechanistically,
      we detected that in the absence of TREM-2, pulmonary macrophages selectively
      produced elevated complement component 1q (C1q) levels. We found that these
      increased C1q levels depended on peroxisome proliferator-activated receptor-delta
      (PPAR-delta) activity and were responsible for the enhanced phagocytosis of
      bacteria. Upon infection with S. pneumoniae, Trem-2(-/-) mice exhibited an
      augmented bacterial clearance from lungs, decreased bacteremia and improved
      survival compared to their WT counterparts. This work is the first to disclose a
      role for TREM-2 in clinically relevant respiratory tract infections and
      demonstrates a previously unknown link between TREM-2 and opsonin production
      within the lungs.

PMID- 24945407
TI  - A quantitative comparison of anti-HIV gene therapy delivered to hematopoietic
      stem cells versus CD4+ T cells.
AB  - Gene therapy represents an alternative and promising anti-HIV modality to highly
      active antiretroviral therapy. It involves the introduction of a protective gene
      into a cell, thereby conferring protection against HIV. While clinical trials to
      date have delivered gene therapy to CD4+T cells or to CD34+ hematopoietic stem
      cells (HSC), the relative benefits of each of these two cellular targets have not
      been conclusively determined. In the present analysis, we investigated the
      relative merits of delivering a dual construct (CCR5 entry inhibitor + C46 fusion
      inhibitor) to either CD4+T cells or to CD34+ HSC. Using mathematical modelling,
      we determined the impact of each scenario in terms of total CD4+T cell counts
      over a 10 year period, and also in terms of inhibition of CCR5 and CXCR4 tropic
      virus. Our modelling determined that therapy delivery to CD34+ HSC generally
      resulted in better outcomes than delivery to CD4+T cells. An early one-off
      therapy delivery to CD34+ HSC, assuming that 20% of CD34+ HSC in the bone marrow
      were gene-modified (G+), resulted in total CD4+T cell counts >= 180 cells/ uL in
      peripheral blood after 10 years. If the uninfected G+ CD4+T cells (in addition to
      exhibiting lower likelihood of becoming productively infected) also exhibited
      reduced levels of bystander apoptosis (92.5% reduction) over non gene-modified (G
      ) CD4+T cells, then total CD4+T cell counts of >= 350 cells/ uL were observed
      after 10 years, even if initially only 10% of CD34+ HSC in the bone marrow
      received the protective gene. Taken together our results indicate that: 1.)
      therapy delivery to CD34+ HSC will result in better outcomes than delivery to
      CD4+T cells, and 2.) a greater impact of gene therapy will be observed if G+
      CD4+T cells exhibit reduced levels of bystander apoptosis over G- CD4+T cells.

PMID- 24945408
TI  - A multi-methodological MR resting state network analysis to assess the changes in
      brain physiology of children with ADHD.
AB  - The purpose of this work was to highlight the neurological differences between
      the MR resting state networks of a group of children with ADHD (pre-treatment)
      and an age-matched healthy group. Results were obtained using different image
      analysis techniques. A sample of n = 46 children with ages between 6 and 12 years
      were included in this study (23 per cohort). Resting state image analysis was
      performed using ReHo, ALFF and ICA techniques. ReHo and ICA represent
      connectivity analyses calculated with different mathematical approaches. ALFF
      represents an indirect measurement of brain activity. The ReHo and ICA analyses
      suggested differences between the two groups, while the ALFF analysis did not.
      The ReHo and ALFF analyses presented differences with respect to the results
      previously reported in the literature. ICA analysis showed that the same resting
      state networks that appear in healthy volunteers of adult age were obtained for
      both groups. In contrast, these networks were not identical when comparing the
      healthy and ADHD groups. These differences affected areas for all the networks
      except the Right Memory Function network. All techniques employed in this study
      were used to monitor different cerebral regions which participate in the
      phenomenological characterization of ADHD patients when compared to healthy
      controls. Results from our three analyses indicated that the cerebellum and mid
      frontal lobe bilaterally for ReHo, the executive function regions in ICA, and the
      precuneus, cuneus and the clacarine fissure for ALFF, were the "hubs" in which
      the main inter-group differences were found. These results do not just help to
      explain the physiology underlying the disorder but open the door to future uses
      of these methodologies to monitor and evaluate patients with ADHD. 

PMID- 24945409
TI  - A severe case of Buruli ulcer disease with pleural effusions.

PMID- 24945411
TI  - High reinfection rate after preventive chemotherapy for fishborne zoonotic
      trematodes in Vietnam.
AB  - BACKGROUND: The World Health Organization aims for complete morbidity control of
      fishborne zoonotic trematodes (FZT) in endemic areas by 2020. The main
      intervention tool for achieving this goal is regular use of preventive
      chemotherapy by offering praziquantel to those at risk in endemic areas. The
      purpose of this study was to investigate the effectiveness of preventive
      chemotherapy to control FZT in an endemic area in Northern Vietnam. METHODOLOGY
      AND PRINCIPLE FINDINGS: We followed a cohort of 396 people who fulfilled the
      criteria for receiving preventive chemotherapy. Stool samples were examined by
      Kato-Katz technique for the presence of trematode eggs before, and two, 16, 29
      and 60 weeks after preventive chemotherapy. The prevalence of trematode eggs in
      stool was 40.2% before, 2.3% two weeks after and increased to a cumulative
      prevalence of 29.8% sixty weeks after preventive chemotherapy. CONCLUSIONS: The
      effectiveness of preventive chemotherapy as a main component in control of FZT is
      not well documented in most endemic areas. We found a high reinfection rate
      within the first year after preventive chemotherapy. Since these trematodes are
      zoonoses, preventive chemotherapy may not have sufficient impact alone on the
      transmission to have a lasting effect on the prevalence. Animal reservoirs and
      farm management practices must be targeted to achieve sustainable control of
      fishborne zoonotic trematode infections, hence control programs should consider a
      One Health approach.

PMID- 24945413
TI  - Peptide materials for biomedicine and nanotechnology.

PMID- 24945412
TI  - Minimal intervention for controlling nosocomial transmission of methicillin
      resistant staphylococcus aureus in resource limited setting with high endemicity.
AB  - OBJECTIVE: To control nosocomial transmission of methicillin-resistant
      Staphylococcus aureus (MRSA) in resource-limited healthcare setting with high
      endemicity. METHODS: Three phases of infection control interventions were
      implemented in a University-affiliated hospital between 1-January-2004 and 31
      December-2012. The first phase of baseline period, defined as the first 48-months
      of the study period, when all MRSA patients were managed with standard
      precautions, followed by a second phase of 24-months, when a hospital-wide hand
      hygiene campaign was launched. In the third phase of 36-months, contact
      precautions in open cubicle, use of dedicated medical items, and 2% chlorhexidine
      gluconate daily bathing for MRSA-positive patients were implemented while hand
      hygiene campaign was continued. The changes in the incidence rates of hospital
      acquired MRSA-per-1000-patient admissions, per-1000-patient-days, and per-1000
      MRSA-positive-days were analyzed using segmented Poisson regression (an
      interrupted time series model). Usage density of broad-spectrum antibiotics was
      monitored. RESULTS: During the study period, 4256 MRSA-positive patients were
      newly diagnosed, of which 1589 (37.3%) were hospital-acquired. The reduction of
      hospital-acquired MRSA per 1000-patient admissions, per 1000-patient-days, and
      per 1000-MRSA-positive-days from phase 1 to 2 was 36.3% (p<0.001), 30.4%
      (p<0.001), and 19.6% (p = 0.040), while the reduction of hospital-acquired MRSA
      per 1000-patient admissions, per 1000-patient-days, and per 1000-MRSA-positive
      days from phase 2 to 3 was 27.4% (p<0.001), 24.1% (p<0.001), and 21.9% (p =
      0.041) respectively. This reduction is sustained despite that the usage density
      of broad-spectrum antibiotics has increased from 132.02 (phase 1) to 168.99 per
      1000 patient-days (phase 3). CONCLUSIONS: Nosocomial transmission of MRSA can be
      reduced with hand hygiene campaign, contact precautions in open cubicle, and 2%
      chlorhexidine gluconate daily bathing for MRSA-positive despite an increasing
      consumption of broad-spectrum antibiotics.

PMID- 24945416
TI  - Low-grade chronic inflammation perpetuated by modern diet as a promoter of
      obesity and osteoporosis.
AB  - Some of the universal characteristics of pre-agricultural hominin diets are
      strikingly different from the modern human diet. Hominin dietary choices were
      limited to wild plant and wild animal foods, while the modern diet includes more
      than 70 % of energy consumed from refined sugars, refined vegetable oils, and
      highly processed cereals and dairy products. The modern diet, with higher intake
      of fat has also resulted in a higher ratio of omega-6 (n-6) to omega-3 (n-3)
      polyunsaturated fatty acids (PUFA), contributing to low-grade chronic
      inflammation (LGCI) and thus promoting the development of many chronic diseases,
      including obesity and osteoporosis. In this review, we describe the changes in
      modern diet, focusing on the kind and amount of consumed fat; explain the
      shortcomings of the modern diet with regard to inflammatory processes; and
      delineate the reciprocity between adiposity and inflammatory processes, with
      inflammation being a common link between obesity and osteoporosis. We present the
      evidence that overconsumption of n-6 PUFA coupled with under-consumption of n-3
      PUFA results in LGCI and, along with the increased presence of reactive oxygen
      species, leads to a shift in mesenchymal stem cells (precursors for both
      osteoblasts and adipocytes) lineage commitment toward increased adipogenesis and
      suppressed osteoblastogenesis. In turn, high n-6 to n-3 PUFA ratios in the modern
      diet, coupled with increased synthesis of pro-inflammatory cytokines due to
      adiposity, propagate obesity and osteoporosis by increasing or maintaining LGCI.

PMID- 24945415
TI  - Total synthesis and structure-activity relationship of glycoglycerolipids from
      marine organisms.
AB  - Glycoglycerolipids occur widely in natural products, especially in the marine
      species. Glycoglycerolipids have been shown to possess a variety of
      bioactivities. This paper will review the different methodologies and strategies
      for the synthesis of biological glycoglycerolipids and their analogs for
      bioactivity assay. In addition, the bioactivities and structure-activity
      relationship of the glycoglycerolipids are also briefly outlined. 

PMID- 24945417
TI  - Effects of selected essential oils on the growth and production of ochratoxin A
      by Penicillium verrucosum.
AB  - Essential oils from oregano (Origanum vulgare L.), mint (Mentha piperita L.),
      fennel (Foeniculum vulgare Mill.), and pine (Abies alba Mill.) needles and cones,
      and their active substances thymol, carvacrol, menthol, and anisaldehyde were
      tested for antifungal activity against Penicillium verrucosum. The lowest minimal
      inhibitory concentrations (MICs) were achieved for essential oil of oregano,
      followed by carvacrol, thymol, and menthol. These antifungal components were
      further investigated, as the main aim of our study was to elucidate the effect of
      natural antifungals on ochratoxin A production. During 21 days of exposure, the
      growth of P. verrucosum, and subsequently the production of ochratoxin A, was
      fully inhibited by thymol at 1/2 MIC (0.0625 mg mL-1), but menthol at 1/4 and 1/2
      MIC (0.1875 and 3750 mg mL-1) showed no growth inhibition. After 21 days of
      incubation, the greatest inhibitory effect on ochratoxin production (inhibition
      was 96.9 %) was also achieved with thymol at 1/4 MIC (0.0313 mg mL-1). Essential
      oil of oregano (1/4 MIC, 0.2930 MUL mL-1) and carvacrol (1/2 MIC, 0.1953 MUL mL
      1) stimulate production of ochratoxin A at 13.9 % to 28.8 %, respectively. The
      observed antifungal effects depended on the agent, the concentration used, and
      the time of interaction between the agent and P. verrucosum. Our results indicate
      the possibility of using oregano essential oil as a substitute for artificial
      preservatives in certain foods, but further research is needed.

PMID- 24945418
TI  - Evaluation of amphetamine-type stimulant abuse through hair analysis: Results
      from 12 years of work.
AB  - Hair analysis is a reliable tool for detecting long-term exposure to illegal
      drugs, including amphetaminetype stimulants, over periods from a few weeks to a
      few months, depending on the length of the hair used for analysis. Between 2000
      and 2012, over 600 hair samples were analysed at the Institute for Medical
      Research and Occupational Health, Croatia (IMROH) for the presence of amphetamine
      type stimulants. IMROH has used the same procedure for testing hair samples for
      amphetamine-type stimulants for over twelve years. It was found to be reliable
      for confirming repeated abuse of amphetamine-type stimulants. Gas
      chromatography/mass spectrometry (GC/MS) was used to determine amphetamine,
      methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4
      methylenedioxymethamphetamine (MDMA-Ecstasy), and 3,4
      methylenedioxyethylamphetamine (MDEA) in hair. Hair samples were either taken at
      the Institute, delivered by mail or a third person brought them to the
      laboratory. In most cases, the hair samples were tested anonymously. A total of
      23 % of the tested samples were positive for one or more amphetamine-type
      stimulant. MDMA was the most frequently detected substance, whereas the most
      frequent combination was amphetamine with MDMA. Our results could indicate a
      trend in amphetamine-type stimulant abuse among young people in the Republic of
      Croatia.

PMID- 24945419
TI  - Sex differences in the fetal heart rate variability indices of twins.
AB  - AIMS: To evaluate the differences in linear and complex heart rate dynamics in
      twin pairs according to fetal sex combination [male-female (MF), male-male (MM),
      and female-female (FF)]. METHODS: Fourteen twin pairs (6 MF, 3 MM, and 5 FF) were
      monitored between 31 and 36.4 weeks of gestation. Twenty-six fetal heart rate
      (FHR) recordings of both twins were simultaneously acquired and analyzed with a
      system for computerized analysis of cardiotocograms. Linear and nonlinear FHR
      indices were calculated. RESULTS: Overall, MM twins presented higher intrapair
      average in linear indices than the other pairs, whereas FF twins showed higher
      sympathetic-vagal balance. MF twins exhibited higher intrapair average in entropy
      indices and MM twins presented lower entropy values than FF twins considering the
      (automatically selected) threshold rLu. MM twin pairs showed higher intrapair
      differences in linear heart rate indices than MF and FF twins, whereas FF twins
      exhibited lower intrapair differences in entropy indices. CONCLUSIONS: The
      results of this exploratory study suggest that twins have sex-specific
      differences in linear and nonlinear indices of FHR. MM twins expressed signs of a
      more active autonomic nervous system and MF twins showed the most active
      complexity control system. These results suggest that fetal sex combination
      should be taken into consideration when performing detailed evaluation of the FHR
      in twins.

PMID- 24945420
TI  - Thrombophilia testing in pregnancy: should we agree to disagree?
AB  - The value of testing for inherited thrombophilia in pregnancy has been debated in
      literature with regard to its utility in preventing adverse obstetrical outcomes
      or identifying women at risk for it. In this commentary, an evidence based
      approach is used to investigate the strength of association between
      thrombophilias and recurrent pregnancy loss and stillbirth. Several studies and
      meta-analyses have shown that there is only a weak association with recurrent
      pregnancy loss. However, many of these studies were underpowered, and there was
      significant heterogeneity-issues that are addressed in this paper. The evidence
      for association with stillbirth is lacking, but the few studies that are
      available seem to suggest a stronger correlation than for recurrent pregnancy
      loss. Further, the benefit of treating thrombophilias with anticoagulation in
      order to prevent these outcomes is discussed. While there is a lack of evidence
      looking at whether anticoagulation prevents stillbirth, there is strong evidence
      to show that anticoagulation does not prevent recurrent pregnancy loss. Finally,
      guidelines put out by various obstetrical and hematological societies regarding
      this topic are summarized.

PMID- 24945421
TI  - Polyglandular autoimmune syndrome type I - a novel AIRE mutation in a North
      American patient.
AB  - Autoimmune polyglandular syndrome type 1 (APS-1), also referred to as autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare
      autoimmune disease that results from autosomal recessive mutations of the human
      autoimmune regulatory (AIRE) gene. We present the case of a 17-year-old North
      American girl of primarily Norwegian descent with a novel AIRE gene mutation
      causing APS-1. In addition to the classic triad of chronic candidiasis,
      hypoparathyoidism and autoimmune adrenocortical insufficiency, she also has
      vitiligo, intestinal malabsorption, autoimmune hepatitis, autoimmune
      hypothyroidism, myositis, myalgias, chronic fatigue, and failure to thrive.
      Genetic testing revealed heterozygosity for c.20_115de196 and c.967_979del13
      mutations in the AIRE gene. The AIRE gene c.20_115de196 mutation has not been
      previously reported.

PMID- 24945422
TI  - Long-term outcomes of pediatric Graves' disease.
AB  - BACKGROUND: Remission rates with antithyroid drugs (ATDs) in pediatric Graves'
      disease (GD) are low. Very few studies report long-term follow-up of GD
      especially into adulthood. OBJECTIVES: We studied long-term outcomes of pediatric
      onset GD, including a follow-up into adulthood and factors associated with need
      for definitive therapy. METHODS: Sixty-five patients (57 females) with GD, with
      onset <18 years (median 13, range, 3.5-17) and duration >=2 years (median 7;
      range, 2-22) since diagnosis, were included. Medical records were reviewed, and
      current details were recorded in a questionnaire by telephonic interview.
      RESULTS: All patients were initially treated with ATDs. Fifty-three patients were
      treated for >=2 years. Amongst these, outcomes included relapse after initial
      remission (n=38), failure of remission (n=8) and long-term remission, defined as
      remission lasting >=4 years (n=6). One patient had carbimazole and surgery but
      died of hepato-renal failure secondary to systemic vasculitis. A total of 44/65
      patients were managed with definitive treatment. Those needing definitive
      treatment had higher mean free T4 (54.6+/-23.7 vs. 39.5+/-20.5 pmol/L, p=0.02)
      and thyrotropin receptor antibody (TRAB) titers (34.1+/-19.3 vs. 13.8+/-9.9 IU/L
      p<0.0001). Long-term sequelae included need for thyroxine replacement (n=42,
      64.6%), persistent goiter (12/62, 19.3%) and persistent ophthalmopathy (19/40,
      47.5%). CONCLUSIONS: Long-term remission rates of pediatric onset GD with ATDs
      are very low, especially with longer follow-up. Higher pretreatment free T4 and
      high TRAB titers predict need for definitive treatment.

PMID- 24945423
TI  - Clinical characteristics and chromosome 11p15 imprinting analysis of Silver
      Russell syndrome - a Chinese experience.
AB  - BACKGROUND: Silver-Russell syndrome (SRS) is an imprinting defect disease. This
      is the first study of Chinese children with SRS caused by chromosome 11p15
      imprinting defects. METHODS: Twenty-five SRS cases, diagnosed in Beijing
      Children's Hospital from 2006 to 2012, were studied retrospectively to detect
      chromosome 11p15 imprinting defects. RESULTS: Over 80% of the children had (i)
      small for gestational age and postnatal growth retardation (mean height standard
      deviation score [HT SDS] was -3.56), (ii) mean body mass index (BMI) SDS was 
      2.10, and (iii) skeletal malformation. Chromosome 11p15 imprinting defects were
      examined in 16 of the 25 patients. Six had hypomethylation in chromosome 11p15
      imprinting control region 1 (ICR1) of the paternal allele; one had
      hypomethylation in chromosome 11p15 ICR1 and hypermethylation in imprinting
      control region 2 (ICR2). Another patient had a duplicated maternal chromosome
      11p15 fragment. Six patients had been treated with for 3-24 months. Growth rates
      ranged from 4 to 10.8 cm/year. CONCLUSIONS: This study demonstrated that Chinese
      children with SRS had more growth retardation than bone retardation, severely low
      levels of BMI, triangular faces, and limb asymmetry. Chromosome 11p15 imprinting
      defects contributed to 50% of these cases, and ICR1 hypomethylation was
      associated with asymmetry.

PMID- 24945424
TI  - Pseudohypoparathyroidism vs. tricho-rhino-phalangeal syndrome: patient
      reclassification.
AB  - OBJECTIVES: Given that tricho-rhino-phalangeal syndrome (TRPS) and
      pseudohypoparathyroidism/pseudopseudohypoparathyroidism (PHP/PPHP) are very rare
      monogenic disorders that share some features (distinctive facies, short stature,
      brachydactyly and, in some patients, intellectual disability) that lead to their
      misdiagnosis in some cases, our objective was to identify clinical, biochemical
      or radiological signs that could help to distinguish these two syndromes. METHODS
      AND RESULTS: We report on two cases, which were referred to the Endocrinology and
      Pediatric Endocrinology Services for obesity. Clinical evaluation initially
      suggested the diagnosis of PHP-Ia [phenotype suggestive of Albright hereditary
      osteodystrophy (AHO) with parathyroid hormone (PTH) resistance] and PPHP
      (phenotype resembling AHO, without PTH resistance), but (epi)genetic analysis of
      the GNAS locus ruled out the suspected diagnosis. Further clinical re-evaluation
      prompted us to suspect TRPS, and this was confirmed genetically. CONCLUSION: TRPS
      was mistakenly identified as PHP/PPHP because of the coexistence of obesity and
      brachydactyly, with PTH resistance in one of the cases. Specific traits such as
      sparse scalp hair and a pear-shaped nose, present in both cases, can be
      considered pathognomonic signs of TRPS, which could help us to reach a correct
      diagnosis.

PMID- 24945425
TI  - A nonsense thyrotropin receptor gene mutation (R609X) is associated with
      congenital hypothyroidism and heart defects.
AB  - Congenital hypothyroidism (CH), one of the most important preventable causes of
      mental retardation, is a clinical condition characterized by thyroid hormone
      deficiency in newborns. CH is most often caused by defects in thyroid development
      leading to thyroid dysgenesis. The thyroid-stimulating hormone receptor (TSHR) is
      the main known gene causing thyroid dysgenesis in consanguineous families with
      CH. In this study, we aim to determine the genetic alteration in a case with
      congenital hypothyroidism and heart defects coming from a consanguineous family.
      We utilized genetic linkage analysis and direct sequencing to achieve our aim.
      Our results revealed that the family showed linkage to the TSHR locus, and we
      detected a homozygous nonsense mutation (R609X) in the case. Apart from other
      cases with the same mutation, our case had accompanying cardiac malformations.
      Although cardiac malformations are not uncommon in sporadic congenital
      hypothyroidism, here, they are reported for the first time with R609X mutation in
      a familial case.

PMID- 24945427
TI  - Congenital hyperinsulinism in a newborn with a novel homozygous mutation
      (p.Q392H) in the ABCC8 gene.
AB  - Congenital hyperinsulinism is the most frequent cause of persistent hypoglycemia
      in infancy. We present the case of a preterm, large-for-gestation-age infant with
      congenital hyperinsulinism who was found to have a novel p.Q392H homozygous
      mutation in the ABCC8 gene. The patient had severe brain damage, despite early
      diagnosis and appropriate management. The new mutations may provide an
      understanding of the prognosis and treatment of the disease. In addition, the
      data will help the family make informed decisions about future pregnancies.

PMID- 24945426
TI  - Association of serum 25-hydroxyvitamin D with race/ethnicity and constitutive
      skin color in urban schoolchildren.
AB  - The objective of this study was to determine the extent to which constitutive
      skin color explains racial/ethnic differences in serum 25-hydroxyvitamin D
      (25OHD) concentrations in urban schoolchildren. Analysis of covariance (ANCOVA)
      was used to determine associations of 25OHD with parent-reported race/ethnicity
      and constitutive skin color as measured by reflectance colorimeter [individual
      typology angle (ITA degrees ; higher value corresponds to lighter skin)] in 307
      Greater Boston schoolchildren aged 9-15 during October-December 2011. Nearly 60%
      of all children were inadequate in 25OHD (<20 ng/mL). Prevalence of inadequate
      25OHD differed by race/ethnicity (p<0.001): white (46.6%), black (74.5%),
      Hispanic (64.7%), Asian (88.9%), and multi-racial/other (52.7%). Serum 25OHD
      increased 0.6 ng/mL per 10 degrees  increase in ITA degrees  value (p<0.001). The
      prediction of 25OHD by race/ethnicity was slightly stronger than the prediction
      by skin color in separate models (R2=0.19, R2=0.16, respectively). Most of the
      variability in 25OHD in race/ethnicity was due to constitutive skin color in this
      group of racially diverse US children.

PMID- 24945428
TI  - Results of first proficiency test for KRAS testing with formalin-fixed, paraffin
      embedded cell lines in China.
AB  - BACKGROUND: Laboratory testing for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral
      oncogene homolog) mutations in metastatic colorectal cancer (mCRC) is performed
      by various methods in China, but there is no standardized system for proficiency
      testing or assay performance evaluations. The aim of this study was to evaluate
      assay and laboratory performance with artificial samples derived from formalin
      fixed, paraffin-embedded (FFPE) cell lines. METHODS: Artificial FFPE samples were
      prepared from cultured cell lines to construct a proficiency panel of 10 samples
      covering eight KRAS mutations and two wild-type samples. The samples were
      validated by Sanger sequencing and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS). The panel was distributed to
      participating laboratories and their reported results were compared to the
      reference sequences. RESULTS: The percentages of mutant KRAS alleles in each
      mutant sample were more than 50% by MALDI-TOF-MS. Sixty-three laboratories
      reported results, including 41 hospital laboratories and 22 commercial
      laboratories and reagent manufacturers. Only 55.6% (35/63) of the laboratories
      correctly identified the mutations in all samples and 33.3% (21/63) reported at
      least one false-positive result. The false-positive ratio was 7.1% (45/630) and
      the false-negative ratio was 3.0% (15/504). CONCLUSIONS: KRAS mutations can be
      missed even by the most sensitive methods if the procedures are not performed
      correctly. False-positive results are a substantial problem in KRAS testing;
      laboratories must use sufficient negative controls to identify cross
      contamination from PCR-amplified products or between samples during handling and
      DNA extraction.

PMID- 24945430
TI  - Red blood cell distribution width: a potential prognostic index for liver
      disease?

PMID- 24945429
TI  - Serum reference intervals of homoarginine, ADMA, and SDMA in the study of health
      in Pomerania.
AB  - BACKGROUND: Low circulating homoarginine as well as high levels of asymmetric
      dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been
      associated with impaired cardiovascular (CV) outcome and mortality in patients at
      risk and in the general population. The present study aimed to formulate
      reference intervals for serum homoarginine, ADMA, and SDMA to improve risk
      stratification between healthy individuals and individuals at risk. METHODS: We
      determined age- and sex-specific reference intervals for homoarginine, ADMA, and
      SDMA in a subgroup of 1359 healthy participants (no diabetes mellitus, CV
      disease, increased blood pressure, elevated blood lipids, chronic kidney disease
      stadium III or IV, or a body mass index >30) of the Study of Health in Pomerania
      (SHIP) using quantile regression analyses. Homoarginine, ADMA, and SDMA serum
      concentrations were measured using liquid chromatography-tandem mass
      spectrometry. RESULTS: Median age of the investigated cohort was 36 (25th; 75th
      percentile 28; 47) years, with 62% women. Median serum concentrations of
      homoarginine, ADMA, and SDMA were 2.63 (2.08; 3.32) MUmol/L, 0.64 (0.57; 0.73)
      MUmol/L, and 0.43 (0.37; 0.49) MUmol/L, respectively. Serum levels of
      homoarginine, ADMA, and SDMA showed material age- and sex-related differences
      (p<0.05 for all). Overall reference ranges were 1.41-5.00 and 1.20-5.53 MUmol/L
      (2.5th; 97.5th percentile; for men and women, respectively) for homoarginine,
      0.41-0.95 and 0.43-0.96 MUmol/L for ADMA, and 0.30-0.67 and 0.27-0.63 MUmol/L for
      SDMA. CONCLUSIONS: We formulated for the first time homoarginine, ADMA, and SDMA
      reference intervals in serum. These reference intervals might be useful for
      individual CV risk stratification.

PMID- 24945431
TI  - ABO blood group and von Willebrand factor: biological implications.
AB  - ABO blood group antigens are complex carbohydrate molecules expressed on the
      surface of red blood cells and a variety of human cells and tissues. It is well
      known that ABO blood type exerts a profound influence on hemostasis, being a
      major determinant of von Willebrand factor (VWF), and consequently factor VIII,
      plasma levels. In this review, we will focus on the molecular mechanisms
      underlying the interaction between ABO blood group and VWF in normal and
      pathological conditions.

PMID- 24945432
TI  - Red blood cell distribution width (RDW) and human pathology. One size fits all.

PMID- 24945433
TI  - Destruction of the hepatocyte junction by intercellular invasion of Leptospira
      causes jaundice in a hamster model of Weil's disease.
AB  - Weil's disease, the most severe form of leptospirosis, is characterized by
      jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by
      pathogenic Leptospira remain unclear. We therefore aimed to elucidate the
      mechanisms by integrating histopathological changes with serum biochemical
      abnormalities during the development of jaundice in a hamster model of Weil's
      disease. In this work, we obtained three-dimensional images of infected hamster
      livers using scanning electron microscope together with freeze-cracking and cross
      cutting methods for sample preparation. The images displayed the corkscrew-shaped
      bacteria, which infiltrated the Disse's space, migrated between hepatocytes,
      detached the intercellular junctions and disrupted the bile canaliculi.
      Destruction of bile canaliculi coincided with the elevation of conjugated
      bilirubin, aspartate transaminase and alkaline phosphatase levels in serum,
      whereas serum alanine transaminase and gamma-glutamyl transpeptidase levels
      increased slightly, but not significantly. We also found in ex vivo experiments
      that pathogenic, but not non-pathogenic leptospires, tend to adhere to the
      perijunctional region of hepatocyte couplets isolated from hamsters and initiate
      invasion of the intercellular junction within 1 h after co-incubation. Our
      results suggest that pathogenic leptospires invade the intercellular junctions of
      host hepatocytes, and this invasion contributes in the disruption of the
      junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs
      immediately. Our findings revealed not only a novel pathogenicity of leptospires,
      but also a novel mechanism of jaundice induced by bacterial infection.

PMID- 24945434
TI  - STAT3 modulation to enhance motor neuron differentiation in human neural stem
      cells.
AB  - Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons
      and forms a glial scar, which prevents neural regeneration. Signal transducer and
      activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis
      and scar formation, and thus a fine modulation of STAT3 signaling may help to
      control the excessive gliogenic environment and enhance neural repair. The
      objective of this study was to determine the effect of STAT3 inhibition on human
      neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2
      (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by
      epidermal growth factor (EGF), which correlated with a higher number of motor
      neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors,
      Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2
      primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+
      and microtubule-associated protein 2 (MAP2)+ co-labeled cells. The increased
      motor neuron differentiation was accompanied by a decrease in the number of glial
      fibrillary acidic protein (GFAP)-positive astrocytes. Interestingly, Stattic and
      Niclosamide did not affect the level of STAT3 phosphorylation; rather, they
      perturbed the nuclear translocation of phosphorylated STAT3. In summary, we
      demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and
      that inhibition of STAT3 further increases motor neuron differentiation at the
      expense of astrogliogenesis. Our study thus suggests a potential benefit of
      targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases. 

PMID- 24945435
TI  - Combination of CD34-positive cell subsets with infarcted myocardium-like matrix
      stiffness: a potential solution to cell-based cardiac repair.
AB  - Detection of the optimal cell transplantation strategy for myocardial infarction
      (MI) has attracted a great deal of attention. Commitment of engrafted cells to
      angiogenesis within damaged myocardium is regarded as one of the major targets in
      cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well
      characterized population of stem cells, might represent highly functional
      endothelial progenitor cells and result in the formation of new blood vessels.
      Recently, physical microenvironment (extracellular matrix stiffness) around the
      engrafted cells was found to exert an essential impact on their fate. Stem cells
      are able to feel and respond to the tissue-like matrix stiffness to commit to a
      relevant lineage. Notably, the infarct area after MI experiences a time-dependent
      stiffness change from flexible to rigid. Our previous observations demonstrated
      myocardial stiffness-dependent differentiation of the unselected bone marrow
      derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial
      stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1
      to 2) after MI provided a more favourable physical microenvironment for cell
      specification and cell-based cardiac repair. However, the difference in tissue
      stiffness-dependent cell differentiation between the specific cell subsets
      expressing and no expressing CD34 phenotype remains uncertain. We presumed that
      CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in
      cardiac repair under induction of infarcted myocardium-like matrix stiffness
      compared with CD34-negative cells. If the hypothesis were true, it would
      contribute greatly to detect the optimal cell subsets for cell therapy and to
      establish an optimized therapy strategy for cell-based cardiac repair. 

PMID- 24945436
TI  - The calcium-dependent protein kinase 3 of toxoplasma influences basal calcium
      levels and functions beyond egress as revealed by quantitative phosphoproteome
      analysis.
AB  - Calcium-dependent protein kinases (CDPKs) are conserved in plants and
      apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress
      from the host cell in the presence of a calcium-ionophore. The targets and the
      pathways that the kinase controls, however, are not known. To identify pathways
      regulated by TgCDPK3, we measured relative phosphorylation site usage in wild
      type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry
      using stable isotope-labeling with amino acids in cell culture (SILAC). This
      revealed known and novel phosphorylation events on proteins predicted to play a
      role in host-cell egress, but also a novel function of TgCDPK3 as an upstream
      regulator of other calcium-dependent signaling pathways, as we also identified
      proteins that are differentially phosphorylated prior to egress, including
      proteins important for ion-homeostasis and metabolism. This observation is
      supported by the observation that basal calcium levels are increased in parasites
      where TgCDPK3 has been inactivated. Most of the differential phosphorylation
      observed in CDPK3 mutants is rescued by complementation of the mutants with a
      wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed
      hyperphosphorylation of two targets of a related calcium-dependent kinase
      (TgCDPK1), as well as TgCDPK1 itself, indicating that this latter kinase appears
      to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1
      partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this
      conclusion. These results show that TgCDPK3 plays a pivotal role in regulating
      tachyzoite functions including, but not limited to, egress. 

PMID- 24945438
TI  - Variability of root traits in spring wheat germplasm.
AB  - Root traits influence the amount of water and nutrient absorption, and are
      important for maintaining crop yield under drought conditions. The objectives of
      this research were to characterize variability of root traits among spring wheat
      genotypes and determine whether root traits are related to shoot traits (plant
      height, tiller number per plant, shoot dry weight, and coleoptile length),
      regions of origin, and market classes. Plants were grown in 150-cm columns for 61
      days in a greenhouse under optimal growth conditions. Rooting depth, root dry
      weight, root: shoot ratio, and shoot traits were determined for 297 genotypes of
      the germplasm, Cultivated Wheat Collection (CWC). The remaining root traits such
      as total root length and surface area were measured for a subset of 30 genotypes
      selected based on rooting depth. Significant genetic variability was observed for
      root traits among spring wheat genotypes in CWC germplasm or its subset.
      Genotypes Sonora and Currawa were ranked high, and genotype Vandal was ranked low
      for most root traits. A positive relationship (R2 >= 0.35) was found between root
      and shoot dry weights within the CWC germplasm and between total root surface
      area and tiller number; total root surface area and shoot dry weight; and total
      root length and coleoptile length within the subset. No correlations were found
      between plant height and most root traits within the CWC germplasm or its subset.
      Region of origin had significant impact on rooting depth in the CWC germplasm.
      Wheat genotypes collected from Australia, Mediterranean, and west Asia had
      greater rooting depth than those from south Asia, Latin America, Mexico, and
      Canada. Soft wheat had greater rooting depth than hard wheat in the CWC
      germplasm. The genetic variability identified in this research for root traits
      can be exploited to improve drought tolerance and/or resource capture in wheat.

PMID- 24945439
TI  - Crowding in the city: losing and winning competitors of an invasive bird.
AB  - Invasive species can take advantage of resources unexploited by natives
      (opportunism hypothesis) or they can exploit the same resources but more
      aggressively or efficiently (competition hypothesis), thus impacting native
      species. However, invasive species tend to exploit anthropogenic habitats that
      are inefficiently used by natives such as urban environments. Focusing on the
      ring-necked parakeet (Psittacula krameri), one of the most invasive birds
      worldwide, we combined observations of interspecific aggressions, species
      specific cavity-nest preferences and the spatial distribution of the native
      cavity-nesting vertebrate community to determine the invasion process as well as
      its potential impacts on native species in a Mediterranean city. Our results
      support the competition hypothesis, suggesting that ring-necked parakeets are
      outcompeting native species sharing nest-site preferences. Parakeets initiated
      and won most interspecific aggressions, which were directed towards competitors
      but also towards predators. This behaviour could explain the spatial arrangement
      of natives, with most bird species breeding close to parakeets possibly to take
      advantage of their effective antipredatory behaviour. However, temporal and
      spatial patterns of segregation suggest that a threatened bat species is
      negatively affected by parakeets. This demonstrates that common species gain
      benefits and threatened ones (in this study, a bat and possibly a falcon) lose
      nest sites due to invaders. Therefore, the conservation status of the native
      species that pay the costs of competition with invaders should be considered.
      This scenario of winners and losers may, however, shift towards more losers if
      the ring-necked parakeet population continues to grow, thus requiring close
      monitoring and control/eradication programs to avoid further impacts. 

PMID- 24945440
TI  - In utero stem cell and gene therapy: current status and future perspectives.
AB  - Advances in prenatal diagnosis have led to the development of fetal therapies for
      congenital disorders. Although in utero surgical intervention has been used
      successfully for correction of anatomical defects that cause fetal demise or long
      term disability, its clinical indications remain limited. In contrast, prenatal
      stem cell and gene therapy might have tremendous potential to treat multiple
      inherited disorders, and could dramatically expand the use of fetal intervention
      to a wide range of anticipated pediatric and adult diseases. Despite encouraging
      results from studies in animal models of disease, the clinical utility of such
      therapies has been restricted by poor efficacy and concerns about safety. The aim
      of this review is to summarize experimental progress toward clinical application
      of in utero stem cell transplantation and gene transfer for the treatment of
      congenital disease. 

PMID- 24945437
TI  - Altered goblet cell differentiation and surface mucus properties in Hirschsprung
      disease.
AB  - Hirschsprung disease-associated enterocolitis (HAEC) leads to significant
      mortality and morbidity, but its pathogenesis remains unknown. Changes in the
      colonic epithelium related to goblet cells and the luminal mucus layer have been
      postulated to play a key role. Here we show that the colonic epithelium of both
      aganglionic and ganglionic segments are altered in patients and in mice with
      Hirschsprung disease (HSCR). Structurally, goblet cells were altered with
      increased goblet cell number and reduced intracellular mucins in the distal colon
      of biopsies from patients with HSCR. Endothelin receptor B (Ednrb) mutant mice
      showed increased goblet cell number and size and increased cell proliferation
      compared to wild-type mice in aganglionic segments, and reduced goblet cell size
      and number in ganglionic segments. Functionally, compared to littermates, Ednrb-/
      mice showed increased transepithelial resistance, reduced stool water content
      and similar chloride secretion in the distal colon. Transcript levels of goblet
      cell differentiation factors SPDEF and Math1 were increased in the distal colon
      of Ednrb-/- mice. Both distal colon from Ednrb mice and biopsies from HSCR
      patients showed reduced Muc4 expression as compared to controls, but similar
      expression of Muc2. Particle tracking studies showed that mucus from Ednrb-/-
      mice provided a more significant barrier to diffusion of 200 nm nanoparticles as
      compared to wild-type mice. These results suggest that aganglionosis is
      associated with increased goblet cell proliferation and differentiation and
      subsequent altered surface mucus properties, prior to the development of
      inflammation in the distal colon epithelium. Restoration of normal goblet cell
      function and mucus layer properties in the colonic epithelium may represent a
      therapeutic strategy for prevention of HAEC. 

PMID- 24945441
TI  - Stem cell therapy as an option for pediatric surgical conditions.
AB  - Regenerative medicine aims to replace, repair, or restore normal function of
      cells, tissues, and organs that are damaged by disease and holds a promising
      potential for the treatment of congenital anomalies. Herein, we present an
      overview of the different stem cell populations and discuss the potentials and
      most recent updates in stem cell therapy relevant to pediatric surgeons. In
      particular, we focus on stem cell applications in intestinal regeneration for
      necrotizing enterocolitis, liver regeneration in biliary atresia and human
      hepatocyte transplantation for liver failure, and pulmonary regeneration of
      hypoplastic lungs due to prematurity or congenital diaphragmatic hernia. 

PMID- 24945442
TI  - Characterizing storm-event nitrate fluxes in a fifth order suburbanizing
      watershed using in situ sensors.
AB  - Land use influences the distribution of nonpoint nitrogen (N) sources in
      urbanizing watersheds and storm events interact with these heterogeneous sources
      to expedite N transport to aquatic systems. In situ sensors provide high
      frequency and continuous measurements that may reflect storm-event N variability
      more accurately compared to grab samples. We deployed sensors from April to
      December 2011 in a suburbanizing watershed (479 km2) to characterize storm-event
      nitrate-N (NO3-N) and conductivity variability. NO3-N concentrations exhibited
      complex patterns both within and across storms and shifted from overall dilution
      (source limitation) before summer baseflows to subsequent periods of flushing
      (transport limitation). In contrast, conductivity generally diluted with
      increasing runoff. Despite diluted NO3-N concentrations, NO3-N fluxes
      consistently increased with flow. Sensor flux estimates for the entire deployment
      period were similar to estimates derived from weekly and monthly grab samples.
      However, significant differences in flux occurred at monthly time scales, which
      may have important implications for understanding impacts to temporally sensitive
      receiving waters. Evidence of both supply (nutrient-poor) and transport (nutrient
      rich) limitation patterns during storms is consistent with watersheds undergoing
      land use transitions. Tracking shifts in these patterns could indicate N
      accumulation in developing watersheds and help identify mitigation opportunities
      prior to N impairment.

PMID- 24945444
TI  - A hydrodynamic comparison of solution and gas phase proteins and their complexes.
AB  - The extent to which protein structures are preserved on transfer from solution to
      gas phase is a central question for native mass spectrometry. Here we compare the
      collision cross sections (Omega) of a wide range of different proteins and
      protein complexes (15-500 kDa) with their corresponding Stokes radii (RS). Using
      these methods, we find that Omega and RS are well correlated, implying overall
      preservation of protein structure in the gas phase. Accounting for protein
      hydration, a scaling term is required to bring Omega and RS into parity.
      Interestingly, the magnitude of this scaling term agrees almost entirely with the
      drag factor proposed by Millikan. RS were then compared with various different
      predicted values of Omega taken from their atomic coordinates. We find that many
      of the approaches used to obtained Omega from atomic coordinates miscalculate the
      physical sizes of the proteins in solution by as much as 20%. Rescaling of Omega
      estimated from atomic coordinates may therefore seem appropriate as a general
      method to bring theoretical values in line with those observed in solution. 

PMID- 24945443
TI  - A rapid RT-PCR assay for the detection of HIV-1 in human plasma specimens.
AB  - INTRODUCTION: The CDC estimates that there are currently over 1million people
      living with human immunodeficiency virus (HIV-1) in the United States, with new
      cases increasing by approximately 50,000 each year. HIV-1 consists of four
      distinct groups: the major M group, and the rare N, O, and P groups, each
      comprising of various subtypes. Without proper care, HIV-1 can lead to
      cardiovascular, kidney, and liver diseases, cancer, and rapid progression into
      acquired immune deficiency syndrome (AIDS). Here, we describe a novel, rapid, and
      highly sensitive assay for the detection of HIV-1 using intercalating dye based
      RT-PCR and melt curve analysis. MATERIALS AND METHODS: We designed an RT-PCR
      assay for the detection of the major M subtypes in addition to the rare (O, N,
      and P) HIV-1 groups, as well as an extraction/RT-PCR control, using melt curve
      analysis. Viral RNA was extracted using the automated Qiagen EZ1 robotic system
      (Qiagen, Valencia, CA). To establish the limit of detection (LOD) for this assay,
      we diluted the AcroMetrix HIV-1 panel (LifeTechnologies, Grand Island, NY) to
      concentrations ranging from 25 to 500 copies/ml. Armored RNA BCR/ABL b3/a2
      (Asuragen, Austin, Texas) was used as our extraction and RT-PCR control.
      Specificity and accuracy were assessed by testing plasma specimens from 48
      anonymized patients negative for HIV-1. RESULTS: This assay has a turnaround time
      of less than 2.5h and has a limit of detection of 50 copies/ml of plasma. Our
      assay also demonstrated 100% concordance with 53 previously quantified plasma
      patient specimens, including 48 negative samples and 5 positive samples. HIV-1
      and our extraction/RT-PCR control were consistently identified at 79  degrees C
      and 82.5  degrees C, respectively. CONCLUSIONS: We developed a comprehensive,
      easy to use assay for the detection of HIV-1 in human plasma. Our assay combines
      a rapid and cost-effective method for molecular diagnostics with the versatility
      necessary for widespread laboratory use. These performance characteristics make
      this HIV-1 detection assay highly suitable for use in a clinical laboratory.

PMID- 24945445
TI  - Enabling women to achieve their breastfeeding goals.

PMID- 24945446
TI  - In reply.

PMID- 24945447
TI  - Loop electrosurgical excision procedure and risk of preterm birth.

PMID- 24945448
TI  - In reply.

PMID- 24945455
TI  - Practice bulletin no. 145: antepartum fetal surveillance.

PMID- 24945449
TI  - Change in sexual behavior with provision of no-cost contraception: health reform
      in action: updates on implementation of the affordable care act.

PMID- 24945456
TI  - Committee opinion no. 605: primary ovarian insufficiency in adolescents and young
      women.
AB  - Primary ovarian insufficiency is the depletion or dysfunction of ovarian
      follicles with cessation of menses before age 40 years. There is no consensus on
      criteria to identify primary ovarian insufficiency in adolescents, and delay in
      diagnosis is common. Health care providers who make this clinical diagnosis
      should be mindful of the sensitive nature of this medical condition. Patients and
      their families should be counseled on the effect of the patient's condition on
      future fertility, on the risk of comorbidities associated with primary ovarian
      insufficiency, and on the condition's potential for genetic inheritance.
      Psychologic counseling also should be offered because impaired self-esteem and
      emotional distress have been reported after diagnosis of primary ovarian
      insufficiency. Once primary ovarian insufficiency is diagnosed, patients should
      be evaluated at least annually. The goals of hormonal therapy extend beyond
      simply symptom relief to levels that support bone, cardiovascular, and sexual
      health. Referrals to a reproductive endocrinology and infertility specialist
      should be made when desired by the patient and family to further discuss
      available reproductive treatments.

PMID- 24945457
TI  - Chiral N-hydroxybenzamides as potential catalysts for aerobic asymmetric
      oxidations.
AB  - Chiral N-hydroxybenzamides (1H-3H) have been synthesized as precursors of chiral
      short-lived N-oxyl radicals 1(*)-3(*). The latter species have been generated by
      oxidation of 1H-3H with Pb(OAc)4 or hydrogen abstraction from 1H-3H by the tert
      butoxyl radical and characterized by UV-vis spectrophotometry and EPR
      spectroscopy. Through a kinetic study of the hydrogen atom transfer processes
      promoted by 1(*)-3(*) from three chiral benzylic substrates (1-phenylethylamine,
      1-phenylethanol, and alpha-vinylbenzyl alcohol), a moderate chiral discrimination
      has been found, with selectivity factors 0.5 <= k(H)(S)/k(H)(R) <= 2.

PMID- 24945458
TI  - Involvement of gene methylation changes in the differentiation of human amniotic
      epithelial cells into islet-like cell clusters.
AB  - Insulin-dependent diabetes results from destruction of the insulin-producing beta
      cells of the pancreas. Islet cell transplantation is a promising cure for
      diabetes. Here, we induced human amniotic epithelial cells (hAECs) to
      differentiate into islet-like cell clusters by nicotinamide plus betacellulin in
      vitro, and further investigated the DNA methylation status by a Nimble MeDIP
      microarray before and after cell differentiation to shed light on the molecular
      mechanisms of this differentiation. In addition, 5-Aza-2'-deoxycytidine was used
      to investigate whether the differentiation of hAECs into islet-like cells
      occurred through demethylation. Purified hAECs (CK18(+)/E
      cadherin(+)/CD29(+)/CD90(-)/CD34(-)/CD45(-)) were isolated from human amnia.
      After induction, hAECs were found to be insulin positive and sensitive to
      glucose, indicating successful induction to islet-like cells. The methylation
      status of cell cytoskeleton-related genes was down-regulated and that of negative
      regulation of cell adhesion-related genes was up-regulated. The methylation
      status of pancreas development-related genes such as HNF1alpha and DGAT1 was
      decreased in hAECs after induction. After brief demethylation, INS gene
      expression was up-regulated in islet-like cell clusters, suggesting that DNA
      methylation changes were associated with the differentiation of hAECs into islet
      like cell clusters. 

PMID- 24945459
TI  - "Seeing is believing": Imaging modalities aid in decision making in end-of-life
      care.

PMID- 24945460
TI  - Histopathological Verification of Osteoimmunological Mediators in Peri
      Implantitis and Correlation to Bone Loss and Implant Functional Period.
AB  - Peri-implantitis (PI) is characterized by inflammation and bone resorption
      eventually leading to implant failure, but the characteristic pathologic
      determinants are undefined to date. This study aims to elucidate the parameters
      involved in PI pathogenesis, including intraoral implant retention time, extent
      of bone loss, smoking history, and identification of osteoimmunological markers
      for inflammation and bone loss. Peri-implant tissues (n = 21) displaying
      clinically diagnosed PI from patients with vertical bone loss ranging from 0-12
      mm and implant function period between 1 and 60 months were evaluated by
      histochemistry and immunohistochemistry for TRAP, CD3, RANK, RANKL, OPG, and TNF
      alpha. Statistical analyses were performed with the Welch test and correlation
      coefficients were calculated. Most bone resorption occurred during the first 12
      months of implant function and correlated with the extent of inflammation,
      although histological signs of inflammation strongly varied between samples from
      minimal appearance of inflammatory cells to extended infiltrates. Implant
      function period and smoking history did not significantly affect the degree of
      inflammation. Higher RANK levels emerged in the first 12 months of implant
      function compared to longer retention times and were negatively correlated to the
      occurrence of RANKL. Additionally, histological signs of inflammation were about
      two-fold higher in specimens with bone resorption up from 5 mm compared to under
      5 mm. CD3(+) cells were more prevalent in extensive inflammatory infiltrates and
      samples derived from smokers. Our analyses proved that PI-induced bone loss is
      differentially influenced by the parameters evaluated in this study, but a
      distinct interconnection between disease severity and implant retention time can
      be established. 

PMID- 24945461
TI  - Novel recessive cone-rod dystrophy caused by POC1B mutation.
AB  - IMPORTANCE: A new form of cone-rod dystrophy (CORD) is described and the gene
      responsible for the disease is identified. OBJECTIVE: To clinically evaluate 4
      patients and 5 control relatives, perform disease gene mapping, and identify the
      gene defect responsible for CORD. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      observational case series of 13 members of a consanguineous family and 113
      unrelated control individuals. INTERVENTIONS: Clinical investigations included
      eye examination with color fundus and autofluorescent imaging, spectral-domain
      optical coherence tomography, and electrophysiologic measurements. Linkage
      mapping was performed using single-nucleotide polymorphism genotype data.
      Candidate genes were analyzed for mutations via Sanger sequencing. MAIN OUTCOMES
      AND MEASURES: Clinical diagnosis of CORD, disease gene mapping, and mutation
      identification. RESULTS: The onset of CORD occurred in early childhood. The
      clinical phenotype was typical CORD with photophobia, decreased central vision,
      and dyschromatopsia. In all patients, a disrupted inner segment/outer segment
      line and the external limiting membrane were noted as a single blurry line at the
      central fovea, and the cone outer segment tip line was absent. In the
      midperipheral retina, the rod inner segment/outer segment line was disrupted and
      blurry, and the rod outer segment tip line was absent. Cone response was
      nonrecordable in all patients, whereas rod response was nonrecordable in the
      eldest patient and subnormal in the others. The Arden Index was abnormal in the
      youngest patient and flat in the others. The disease gene mapped to a less than 2
      megabase recessive locus at 12q21.33 with a logarithm of odds score of 3.92. At
      the locus, we identified a homozygous missense POC1B p.R106P mutation that was
      predicted as damaging by online tools. CONCLUSIONS AND RELEVANCE: POC1B is a
      novel gene for a new disease typical of CORD except that patients did not report
      night blindness. The clinical course was slowly progressive. Screening for POC1B
      mutation could benefit families afflicted with CORD.

PMID- 24945462
TI  - Clines with partial panmixia in an environmental pocket.
AB  - In geographically structured populations, global panmixia can be regarded as the
      limiting case of long-distance migration. The effect of incorporating partial
      panmixia into diallelic single-locus clines (i.e., asymptotically stable
      equilibria) maintained by migration and selection in an isotropic environmental
      pocket in n dimensions is investigated. The population density is uniform.
      Migration and selection are both weak; the former is homogeneous and isotropic;
      the latter is directional. If the scaled panmictic rate beta>=1, then the allele
      favored in the pocket is ultimately lost. For beta<1, a cline is maintained if
      and only if the scaled radius a of the pocket exceeds a critical value an. For a
      step-environment without dominance, simple, explicit formulas are derived for a1
      and a3; an equation with a unique solution and simple, explicit approximations
      are deduced for a2. The ratio of the selection coefficients outside and inside
      the pocket is -alpha. As expected intuitively, the cline becomes more difficult
      to maintain; i.e., the critical radius an increases for n=1,2,3,... as alpha,
      beta, or n increases.

PMID- 24945465
TI  - Angle-resolved synchrotron photoemission and density functional theory on the
      iridium modified Si(1 1 1) surface.
AB  - The physical and electronic properties of the Ir modified Si(1 1 1) surface have
      been investigated with the help of angle resolved photoemission spectroscopy and
      density functional theory. The surface consists of Ir-ring clusters that form a
      [Formula: see text]reconstruction. A comparison between the measured and
      calculated band structure of the system reveals that the dispersions of the
      projected bulk states and the states originating from [Formula: see text] domains
      are heavily modified due to Umklapp scattering from the surface Brillouin zone.
      Density of states calculations show that Ir-ring clusters contribute to the
      states in the vicinity of the Fermi level.

PMID- 24945463
TI  - Stabilizing rescued surface-localized deltaf508 CFTR by potentiation of its
      interaction with Na(+)/H(+) exchanger regulatory factor 1.
AB  - Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in CFTR,
      a plasma-membrane-localized anion channel. The most common mutation in CFTR,
      deletion of phenylalanine at residue 508 (DeltaF508), causes misfolding of CFTR
      resulting in little or no protein at the plasma membrane. The CFTR corrector VX
      809 shows promise for treating CF patients homozygous for DeltaF508. Here, we
      demonstrate the significance of protein-protein interactions in enhancing the
      stability of the DeltaF508 CFTR mutant channel protein at the plasma membrane. We
      determined that VX-809 prolongs the stability of DeltaF508 CFTR at the plasma
      membrane. Using competition-based assays, we demonstrated that DeltaF508 CFTR
      interacts poorly with Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) compared
      to wild-type CFTR, and VX-809 significantly increased this binding affinity. We
      conclude that stabilized CFTR-NHERF1 interaction is a determinant of the
      functional efficiency of rescued DeltaF508 CFTR. Our results demonstrate the
      importance of macromolecular-complex formation in stabilizing rescued mutant CFTR
      at the plasma membrane and suggest this to be foundational for the development of
      a new generation of effective CFTR-corrector-based therapeutics. 

PMID- 24945464
TI  - Pazopanib combined with radiation: in vivo model of interaction.
AB  - OBJECTIVE: Assess interaction of pazopanib, an oral antivascular endothelial
      growth factor inhibitor, with radiation in tumor xenograft models. METHODS: Flank
      xenografts in female athymic nude mice of human lung cancer cell line, A549, and
      head and neck cancer cell line, UM-SCC-6, were allowed to grow to ~5*5 mm. Groups
      were then treated with pazopanib and/or escalating doses of radiation and tumor
      measurements over time compared with untreated tumor-bearing controls. Pazopanib
      (100 mg/kg) began 7 days before radiation and continued for 28 days. Daily
      radiation was 0.5, 1, 2, or 3 Gy *5 days. RESULTS: Tumors in the A549 control
      group reached >4* the original size by day 36 postradiation. All treatment groups
      had less robust tumor growth (p<0.05) and the group receiving pazopanib+3 Gy
      radiation/day had tumor regression to less than baseline. In the UM-SCC-6-tumor
      bearing animals, tumors in all treatment groups had less robust growth than
      untreated controls after day 23 post-treatment. CONCLUSION: The combination of
      pazopanib and radiation resulted in a trend of superior tumor growth inhibition
      compared with either agent alone. All treatment groups had impaired tumor
      progression compared with untreated controls.

PMID- 24945466
TI  - Regulation of cell volume and water transport--an old fundamental role of the
      renin angiotensin aldosterone system components at the cellular level.
AB  - The expression and the role of renin angiotensin aldosterone system (RAAS)
      components on regulation of cell volume and water transport on vertebrates and
      invertebrates were reviewed. The presence of these components even in simple
      organisms like leeches and their relevance for the control of cellular volume and
      water transport supports the view that the expression of these components, at
      cellular level, is an acquisition which was preserved throughout evolution. 

PMID- 24945467
TI  - Long-term health-related quality-of-life in patients with acquired brain injury
      and their caregivers.
AB  - OBJECTIVES: The present study aimed to assess long-term health-related quality-of
      life (HRQoL) and potential predictors as well as burden in caregivers of patients
      with acquired brain injury (ABI). Furthermore, depressive symptoms, well-being,
      HRQoL and happiness were evaluated in caregivers and patients who had regained
      communication skills. RESEARCH DESIGN: Prospective cross-sectional survey.
      METHODS: Data of 104 caregivers and 30 patients were analysed. A multiple linear
      regression model was calculated to identify independent predictors for HRQoL in
      caregivers. Additionally, correlation analysis was conducted to evaluate
      associations between patient questionnaire results and caregiver HRQoL. RESULTS:
      After a mean time post-injury of 18 years, HRQoL and perceived health status in
      caregivers remained below normative scores of age-matched controls. Although
      HRQoL and perceived health status were lower in patients than in caregivers,
      there was no difference in happiness, perceived QoL or enjoyment of life. Reduced
      perception in well-being (WHO-5 score < 13) was found in 52% of the caregivers
      and 36% of the patients. HRQoL in caregivers was predicted by well-being,
      caregiver strain, depressive symptoms and caregiver age. Furthermore, HRQoL of
      caregivers was correlated with depressive symptoms and happiness in patients.
      CONCLUSION: This study under-scores the importance of long-term support for
      caregivers.

PMID- 24945470
TI  - 'People insult her as a sexy woman': sexuality, stigma and vulnerability among
      widowed and divorced women in Oromiya, Ethiopia.
AB  - Widowed and divorced women, sometimes referred to as 'female heads of household',
      are one of the most impoverished and marginalised groups in the world. Widowed
      and divorced women are often overlooked in the literature or are seen primarily
      as economically or socially marginalised beings; their sexuality is rarely
      addressed. In an effort to understand the experiences and challenges faced by
      such women, we conducted and analysed four focus-group discussions, seven in
      depth interviews and four interactive activities with 32 widowed and divorced
      women and with 25 other community members in Oromiya, Ethiopia. Findings indicate
      that women experienced high levels of community stigma in relation to their
      sexuality. Participants' fear of community stigma, and the actions they took to
      avert it, further served to marginalise them within their community and had
      negative impact on their economic, social and health support systems and,
      ultimately, on their overall well-being. Future interventions need to acknowledge
      sexual stigma as a driving force in the many challenges these women face. Further
      programmatic work is needed to reduce stigma related to widowed and divorced
      women's sexuality and to decrease their vulnerability to rape. 

PMID- 24945468
TI  - Mucosal and systemic immunization with a novel attenuated pneumococcal vaccine
      candidate confer serotype independent protection against Streptococcus pneumoniae
      in mice.
AB  - Despite the availability of effective vaccines, Streptococcus pneumoniae is still
      one of the major infectious diseases causing substantial morbidity and mortality
      in children under 5 years old. In this study, we demonstrate the protective
      efficacy of S. pneumoniae SPY1, a novel live attenuated vaccine strain against
      pneumococcal infection in murine models. This strain was characterized by defects
      in three important pneumococcal virulence factors including capsule, teichoic
      acids and pneumolysin. The lactate dehydrogenase assays and in vivo animal
      experiments demonstrated a significantly attenuated virulence and a reduced
      nasopharyngeal colonization for the SPY1 strain. We also show that mucosal and
      systemic immunization with the live SPY1 strain induced protective immune
      responses against pneumococci. Mucosal immunization with SPY1 offered better
      protection against colonization challenge with strains TIGR4 and serotype 19F
      than systemic SPY1 immunization. In invasive infection models, mucosal
      vaccination with the SPY1 strain conferred complete protection against D39 and
      clinical serotype 6B and 3 strains. Notably, intranasal vaccination with the SPY1
      strain conferred superior protection against pneumococcal invasive disease
      compared with the commercial available vaccines. SPY1 strain was shown to elicit
      high levels of serotype-independent antibodies and a mixed cellular immune
      response. Besides, the SPY1 serum was able to passively protect mice against
      invasive challenge with D39 strain, indicating the protective effect of the
      antibody-mediated responses. Together, the SPY1 strain may be a promising live
      vaccine strain to protect pneumococcal infection. 

PMID- 24945471
TI  - Estimating the correlation between bursty spike trains and local field
      potentials.
AB  - To further understand rhythmic neuronal synchronization, an increasingly useful
      method is to determine the relationship between the spiking activity of
      individual neurons and the local field potentials (LFPs) of neural ensembles.
      Spike field coherence (SFC) is a widely used method for measuring the
      synchronization between spike trains and LFPs. However, due to the strong
      dependency of SFC on the burst index, it is not suitable for analyzing the
      relationship between bursty spike trains and LFPs, particularly in high frequency
      bands. To address this issue, we developed a method called weighted spike field
      correlation (WSFC), which uses the first spike in each burst multiple times to
      estimate the relationship. In the calculation, the number of times that the first
      spike is used is equal to the spike count per burst. The performance of this
      method was demonstrated using simulated bursty spike trains and LFPs, which
      comprised sinusoids with different frequencies, amplitudes, and phases. This
      method was also used to estimate the correlation between pyramidal cells in the
      hippocampus and gamma oscillations in rats performing behaviors. Analyses using
      simulated and real data demonstrated that the WSFC method is a promising measure
      for estimating the correlation between bursty spike trains and high frequency
      LFPs. 

PMID- 24945469
TI  - Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against
      estrogen-dependent breast cancer cells.
AB  - Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles
      have become one of the most popular polymeric devices for chemotherapeutic-based
      nanoformulations against several kinds of malignant diseases. Promising
      properties, including long-circulation time, enhanced tumor localization,
      interference with "multidrug" resistance effects, and environmental
      biodegradability, often result in an improvement of the drug bioavailability and
      effectiveness. In the present work, we have synthesized 1,7-bis(3,4
      dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform
      ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a
      single-emulsion process. Structural and morphological features of the
      nanoformulation were analyzed, followed by an accurate evaluation of the in vitro
      drug release kinetics, which exhibited Fickian law diffusion over 10 days. The
      intracellular degradation of ASC-J9-bearing nanoparticles within estrogen
      dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent
      activity of the released drug. A cellular growth inhibition associated with a
      specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the
      cytosol allowed us to put forward a hypothesis on the action mechanism of this
      nanosystem, which led to the final cell apoptosis. Our study was accomplished
      using Annexin V-based cell death analysis, MTT assessment of proliferation,
      radical scavenging activity, and intracellular ROS evaluation. Moreover, the
      intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman
      optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved
      also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a
      possible clinical translation of this potential nanochemotherapeutic to expand
      the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed
      for the treatment of malignant breast cancer. 

PMID- 24945473
TI  - A conversation with AAOS president Frederick M. Azar, MD.

PMID- 24945472
TI  - Neural network for solving Nash equilibrium problem in application of multiuser
      power control.
AB  - In this paper, based on an equivalent mixed linear complementarity problem, we
      propose a neural network to solve multiuser power control optimization problems
      (MPCOP), which is modeled as the noncooperative Nash game in modern digital
      subscriber line (DSL). If the channel crosstalk coefficients matrix is positive
      semidefinite, it is shown that the proposed neural network is stable in the sense
      of Lyapunov and global convergence to a Nash equilibrium, and the Nash
      equilibrium is unique if the channel crosstalk coefficients matrix is positive
      definite. Finally, simulation results on two numerical examples show the
      effectiveness and performance of the proposed neural network. 

PMID- 24945474
TI  - Computer navigation systems in unicompartmental knee arthroplasty: a systematic
      review.
AB  - We conducted a systematic review to consolidate the body of knowledge about use
      of computer navigation systems in unicompartmental knee arthroplasty (UKA), to
      determine whether these systems are useful in UKA, and to discuss the financial
      costs involved. We searched Medline (2002 to 2013) for articles in which results
      of navigated and conventional techniques were compared. In the navigated group,
      implant alignment was optimal in the desired angular range more often, and there
      were fewer outliers. However, the groups did not differ with respect to clinical
      knee scores, survival rates, or range of motion. Longer surgery in the navigation
      group could result in an increase in navigation-related complications. The lack
      of clear evidence of the usefulness of computer-assisted navigation systems in
      UKA has impeded universal acceptance of this technology in the orthopedic
      community. Definitive evidence can be generated only with large randomized
      studies with long-term follow-up.

PMID- 24945475
TI  - Perioperative differences in conventional and computer-assisted surgery in
      bilateral total knee arthroplasty.
AB  - Performing bilateral total knee arthroplasties (bTKAs), sequential or staged, is
      a topic of debate among surgeons. To our knowledge, no studies have compared
      computer-assisted surgery (CAS) and conventional (CON) procedures for sequential
      bTKAs. We retrospectively reviewed 124 (62 CAS, 62 CON) sequential bTKAs. CAS
      bTKAs required significantly fewer blood transfusions (P = .001) and had
      significantly better postoperative day 1 (POD-1) hemoglobin (Hgb) levels (P =
      .001) and POD-2 Hgb levels (P = .01). Mean total blood transfusion units were 0.9
      for the CAS group and 1.7 for the CON group. Postoperative range of motion,
      tourniquet time, length of stay, number of readmissions, and number of
      reoperations were not significantly different (P > .05). The statistically
      significant differences between the groups may have resulted from violation of
      the femoral intramedullary canal during the CON technique.

PMID- 24945476
TI  - Trends in primary and revision anterior cruciate ligament reconstruction among
      National Basketball Association team physicians.
AB  - Anterior cruciate ligament (ACL) tears are common in athletes. Techniques and
      methods of treatment for these injuries continue to vary among surgeons. Thirty
      National Basketball Association (NBA) team physicians were surveyed during the
      NBA Pre-Draft Combine. Survey questions involved current and previous practice
      methods of primary and revision ACL reconstruction, including technique, graft
      choice, rehabilitation, and treatment of combined ACL and medial collateral
      ligament injuries. Descriptive parametric statistics, Fisher exact test, and
      logistic regression were used, and significance was set at alpha = 0.05. All 30
      team physicians completed the survey. Eighty-seven percent indicated they use
      autograft (81% bone-patellar tendon-bone) for primary ACL reconstruction in NBA
      athletes, and 43% indicated they use autograft for revision cases. Fourteen
      surgeons (47%) indicated they use an anteromedial portal (AMP) for femoral tunnel
      drilling, whereas 5 years earlier only 4 (13%) used this technique. There was a
      significant (P = .009) positive correlation between fewer years in practice and
      AMP use. NBA team physicians' use of an AMP for femoral tunnel drilling has
      increased over the past 5 years.

PMID- 24945477
TI  - Delayed presentation of a cervical spine fracture dislocation with posterior
      ligamentous disruption in a gymnast.
AB  - Cervical spine injuries are uncommon but potentially devastating athletic
      injuries. We report a case of a girl gymnast who presented with a cervical spine
      fracture dislocation with posterior ligamentous disruption several days after
      injury. To our knowledge, this type of presentation with such severity of injury
      in a gymnast has not been reported in the literature. The patient was performing
      a double front tuck flip and sustained a hyperflexion, axial-loading injury. She
      experienced mild transient numbness in her bilateral upper and lower extremities
      lasting for about 5 minutes, after which it resolved. The patient was
      neurologically intact during her clinic visit, but she endorsed significant
      midline cervical tenderness. Plain radiographs and computed tomography imaging of
      the cervical spine revealed a C2-C3 fracture dislocation. She underwent posterior
      open reduction followed by C2-C3 facet arthrodesis and internal fixation. This
      case highlights the importance of very careful evaluations of neck injuries and
      the maintenance of high suspicion for significant underlying pathology. 

PMID- 24945478
TI  - Intraoperative fat embolism during core decompression and bone grafting for
      osteonecrosis of the hip: report of 3 cases and literature review.
AB  - Osteonecrosis (ON) of the femoral head, without timely intervention, often
      progresses to debilitating hip arthritis. Core decompression (CD) with bone
      grafting was used to treat patients with early-stage ON. In 3 cases,
      intraoperative oxygen saturation, end-tidal carbon dioxide fluctuations, and/or
      vital sign fluctuations were observed during insertion of the graft, a mixture of
      bone marrow and demineralized bone matrix. In 1 case, continued postoperative
      pulmonary symptoms required admission to intensive care. In this article, we
      describe these cases and provide supporting evidence that they were caused by fat
      emboli secondary to forceful insertion of bone graft. We review the literature
      and present complications data. Although no cases of fat emboli were reported as
      complications of any CD series with or without bone grafting, CD augmented with
      bone graft may carry risks not seen before in CD alone. Care should be taken to
      avoid these complications, possibly through technique modification.

PMID- 24945479
TI  - Progressive valgus angulation of the ankle secondary to loss of fibular congruity
      treated with medial tibial hemiepiphysiodesis and fibular reconstruction.
AB  - The fibula is an important stabilizer of the lateral ankle. Discontinuity of the
      fibular shaft can lead to progressive pain and shortening of the fibula,
      ultimately causing loss of lateral support to the ankle. Two children, who
      sustained segmental bone loss of the shaft of the fibula, developed progressive
      symptomatic valgus of the ankle with widening of the mortice and lateral
      subluxation of the talus. Both patients were treated with fibular plating and
      grafting with tricalcium sulfate with acute reconstitution of fibular length.
      Distal medial tibial hemiepiphysiodesis was simultaneously performed. One patient
      required revision plating and grafting 14 months after the index surgery because
      of plate failure. The valgus angulation and the widened medial mortice were
      corrected in the ankles of both patients, who returned to full activities. The
      patients were followed to maturity; the correction has been maintained, and they
      remain asymptomatic. The technique used in these cases can correct valgus
      angulation secondary to loss of fibular congruity rather than only halting
      progression of the deformity. 

PMID- 24945480
TI  - A novel technique for centering the femoral stem in primary total hip
      arthroplasty.
AB  - Careful surgical technique is a critical component of total hip arthroplasty.
      Femoral preparation and component positioning are vital to improving outcomes and
      preventing complications. Using the starting awl when preparing the femur aids in
      opening and centralizing the canal for sequential reaming or broaching. Although
      traditional techniques can lead to a deviation from midline, a novel technique
      allows the awl to center itself in the canal with little risk for cortical
      perforation. We evaluated 200 patients whose surgeries were performed by a single
      surgeon using the traditional technique (group 1) or a novel technique (group 2)
      and found a statistically significant difference in mean deviation from midline.
      In group 2, the mean deviation was 0.34 degrees ; in group 1, the mean deviation
      was 0.85 degrees . Our novel technique provides a safe, easily reproducible
      approach to using the starter awl in femoral preparation. 

PMID- 24945481
TI  - Billing and coding knowledge: a comparative survey of professional coders,
      practicing orthopedic surgeons, and orthopedic residents.
AB  - Medical knowledge and surgical skills are necessary to become an effective
      orthopedic surgeon. To run an efficient practice, the surgeon must also possess a
      basic understanding of medical business practices, including billing and coding.
      In this study, we surveyed and compared the level of billing and coding knowledge
      among current orthopedic residents PGY3 and higher, academic and private practice
      attending orthopedic surgeons, and orthopedic coding professionals. According to
      the survey results, residents and fellows have a similar knowledge of coding and
      billing, regardless of their level of training or type of business education
      received in residency. Most residents would like formal training in coding,
      billing, and practice management didactics; this is consistent with data from
      previous studies.

PMID- 24945482
TI  - Effect of a preoperative protocol of aerobic physical therapy on the quality of
      life of patients with adolescent idiopathic scoliosis: a randomized clinical
      study.
AB  - Patients with adolescent idiopathic scoliosis (AIS) have lower potential for
      physical activity because of lung dysfunction and lower muscle strength, which
      can be reversed by the cardiorespiratory and musculoskeletal conditioning
      provided by standardized physical activities. We conducted a study to determine
      if a preoperative protocol of aerobic exercise would improve quality of life
      (QoL) both before and after training and if there would be any differences
      between patients who received the therapy and those who did not. Patients with
      the indication of surgical correction of AIS were randomized to receive or not
      receive a 4-month preoperative course of aerobic physical training. At baseline
      and after 4 months, they were evaluated with the Short Form-36 questionnaire (SF
      36). QoL scores improved for the study group but did not change for the control
      group. In all QoL domains, the study group's mean score increased significantly
      between baseline and 4 months. We concluded that the proposed preoperative
      physical therapy protocol improved the QoL of patients with AIS.

PMID- 24945484
TI  - Management of complications following radiofrequency ablation of a pedicle
      osteoid osteoma.
AB  - Radiofrequency ablation (RFA) has become an accepted first-line treatment for
      osteoid osteomas. Ablation of spinal osteoid osteomas has presented a particular
      challenge because of their proximity to delicate neural structures. Although many
      case series have reported multiple successfully treated spinal osteoid osteomas,
      there are no reports of thermal injury or insufficiency fracture associated with
      RFA of spinal osteoid osteomas. We report the management of complications that
      result from treating a spinal osteoid osteoma within a pedicle.

PMID- 24945483
TI  - Risk of hepatitis C virus exposure in orthopedic surgery: is universal screening
      needed?
AB  - The aging baby boomer generation will soon start using tremendous orthopedic
      surgical resources. This group has also been identified as a group at high risk
      for having undiagnosed hepatitis C virus (HCV) infection. We conducted a study to
      assess the prevalence of HCV among orthopedic surgery patients at our institution
      using their demographic data to determine whether they represent a unique cohort
      at high risk for having undiagnosed HCV. We estimated that we operated on as many
      as 233 patients with undiagnosed HCV in 2011. A cost-effective, universal
      preoperative HCV screening program may reduce the risk for occupational exposure
      in orthopedic surgery and significantly benefit public health by bringing
      undiagnosed patients to treatment. A robust screening program requires several
      ethical considerations. By offering routine screening to patients, orthopedic
      surgeons have an opportunity to maintain intraoperative safety and improve the
      health of the public.

PMID- 24945485
TI  - Transition of historial tube flaps to free flap for 2-stage total knee
      arthroplasty in a patient with a history of Gustilo grade IIIB tibia fracture.
AB  - We report the case of a 56-year-old patient who had posttraumatic bilateral knee
      arthritis and underwent sequential bilateral total knee arthroplasty (TKA). The
      left knee joint required 2-stage reconstruction: a free flap for enhanced soft
      tissue coverage and then left knee TKA. Uniquely, at age 16 years this patient
      sustained a left tibia grade IIIB high-energy crush injury in a car crash and
      underwent reconstruction with multiple pedicle tube flaps and transfer of soft
      tissues. Most of that reconstruction was done between the ages of 16 and 19. At
      age 56 years, staged TKA was performed. To our knowledge, this is the first
      report of a knee reconstructed with pedicle tube flaps for a grade IIIB tibial
      fracture, followed years later by free-flap coverage before TKA. This report
      offers insights and treatment recommendations through long-term follow-up of a
      unique case and a historical perspective on how reconstructive options have
      evolved.

PMID- 24945487
TI  - Special section editorial.

PMID- 24945488
TI  - Left atrium function in patients with coronary artery disease.
AB  - PURPOSE OF REVIEW: The left atrial cavity has recently been identified as a
      potential biomarker for cardiac and cerebrovascular accidents. This review
      examines the potential of left atrial size and function in predicting
      cardiovascular disease in the general population and outcomes in coronary artery
      disease (CAD) patients. RECENT FINDINGS: The atrium is perfused primarily by
      branches of the proximal left circumflex coronary artery (LCx), and depression of
      the cavity mechanical performance has been demonstrated in experimental studies
      during LCx occlusion. Thus, left atrial volume and function assessment may have
      prognostic relevance, particularly in CAD patients. Such a line of thinking,
      however, is challenged by the widespread notion that the contribution by left
      atrial chamber morphology and functional quantitation to the risk stratification
      process after a first cardiovascular event is not adequately considered. However,
      a number of studies have shown that left atrial volume predicts survival and
      major adverse events after an acute myocardial infarction. Left atrial remodeling
      also provides an important overall prognostic information and correlates with
      brain natriuretic peptide after primary percutaneous coronary interventions.
      SUMMARY: Evaluation of left atrial size and function is currently of great
      interest and it will be more so in the very near future, given its potential for
      insights into the pathophysiology of the ischemic heart, which makes it an
      important clinical risk identifier in CAD patients.

PMID- 24945486
TI  - Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal
      or sepsis-induced changes in skeletal muscle protein synthesis in male or female
      mice.
AB  - Sepsis decreases skeletal muscle protein synthesis in part by impairing mTOR
      activity and the subsequent phosphorylation of 4E-BP1 and S6K1 thereby
      controlling translation initiation; however, the relative importance of changes
      in these two downstream substrates is unknown. The role of 4E-BP1 (and -BP2) in
      regulating muscle protein synthesis was assessed in wild-type (WT) and 4E-BP1/BP2
      double knockout (DKO) male mice under basal conditions and in response to sepsis.
      At 12 months of age, body weight, lean body mass and energy expenditure did not
      differ between WT and DKO mice. Moreover, in vivo rates of protein synthesis in
      gastrocnemius, heart and liver did not differ between DKO and WT mice. Sepsis
      decreased skeletal muscle protein synthesis and S6K1 phosphorylation in WT and
      DKO male mice to a similar extent. Sepsis only decreased 4E-BP1 phosphorylation
      in WT mice as no 4E-BP1/BP2 protein was detected in muscle from DKO mice. Sepsis
      decreased the binding of eIF4G to eIF4E in WT mice; however, eIF4E*eIF4G binding
      was not altered in DKO mice under either basal or septic conditions. A comparable
      sepsis-induced increase in eIF4B phosphorylation was seen in both WT and DKO
      mice. eEF2 phosphorylation was similarly increased in muscle from WT septic mice
      and both control and septic DKO mice, compared to WT control values. The sepsis
      induced increase in muscle MuRF1 and atrogin-1 (markers of proteolysis) as well
      as TNFalpha and IL-6 (inflammatory cytokines) mRNA was greater in DKO than WT
      mice. The sepsis-induced decrease in myocardial and hepatic protein synthesis did
      not differ between WT and DKO mice. These data suggest overall basal protein
      balance and synthesis is maintained in muscle of mice lacking both 4E-BP1/BP2 and
      that sepsis-induced changes in mTOR signaling may be mediated by a down-stream
      mechanism independent of 4E-BP1 phosphorylation and eIF4E*eIF4G binding. 

PMID- 24945489
TI  - Left atrial volumes: two-dimensional, three-dimensional, cardiac magnetic
      resonance and computed tomography measurements.
AB  - PURPOSE OF REVIEW: Evaluation of left atrial volume is important, as it is a
      biomarker of cardiovascular disease and outcomes and correlates with diastolic
      dysfunction severity. Left atrial volume measurements by different imaging
      modalities, including 2D and 3D echocardiography (2DE and 3DE), cardiac magnetic
      resonance (CMR) and computed tomography (CT), are reviewed in regard to recent
      advances, methodology, prognostic value and limitations. RECENT FINDINGS: Left
      atrial volume assessments correlate well between the different imaging
      modalities; however, 2DE significantly underestimates left atrial measurements.
      Assessment of the left atrial minimum volume and left atrial phasic function
      derived volumetrically have reported superior predictive value for major adverse
      cardiovascular events and elevated left ventricular diastolic pressure compared
      with the left atrial maximum volume. SUMMARY: The different imaging modalities
      used to assess left atrial volumes are not interchangeable, particularly for
      serial measurements. Although 2DE underestimates left atrial volumes, most
      normative as well as predictive data have been obtained using this modality.
      Standardization, with established normative data and classification criteria,
      needs to be established for other imaging modalities, additionally incorporating
      assessment of left atrial minimum and phasic volumes. Despite the limitations of
      the more simplistic 2DE, its measurements are well defined with significant
      prognostic value. The incremental prognostic value of the more complex imaging
      techniques needs to be further validated.

PMID- 24945491
TI  - Patterns of community-based opioid prescriptions in people dying of cancer.
AB  - CONTEXT: Studies of opioid use in cancer patients have been cross-sectional or
      have focused on mean consumption over a specific time interval. OBJECTIVES: This
      study aimed to determine the temporal pattern of prescribed opioids at a
      population level. METHODS: Using Quebec administrative databases, we ascertained
      details of cancer-related deaths and filled community-based opioid prescriptions
      (COPs) in 48,420 decedents from 2003 to 2006. RESULTS: Using group-based
      trajectory modeling, based on when people started to fill COPs, our population
      based study demonstrated patterns of filled COPs with six distinct trajectories.
      An earlier start in opioid consumption resulted in a higher group average
      morphine daily dose; those who were already filling COPs at study entry (5.2%)
      had a final dose of more than 300mg by the time of death. Remarkably, 58.8% of
      people had not filled COPs with a biweekly average greater than 1mg earlier than
      two weeks before death, marking the end of follow-up. Breast cancer in women,
      prostate or colorectal cancer in men, and younger age and multiple myeloma in
      both sexes were positively associated with earlier filling of COPs. CONCLUSION:
      Patients dying of cancer require increasing doses of opioids over time; although
      we cannot distinguish the relative contributions of disease progression and
      opioid tolerance, age and certain cancers seem related to this phenomenon. Given
      the potentially prohibitive cost of prospective epidemiological studies, more
      elaborate clinical administrative databases that include regular pain assessment
      are necessary to determine optimal opioid use and factors associated with dose
      increases over time at a population level.

PMID- 24945490
TI  - The POU factor ventral veins lacking/Drifter directs the timing of metamorphosis
      through ecdysteroid and juvenile hormone signaling.
AB  - Although endocrine changes are known to modulate the timing of major
      developmental transitions, the genetic mechanisms underlying these changes remain
      poorly understood. In insects, two developmental hormones, juvenile hormone (JH)
      and ecdysteroids, are coordinated with each other to induce developmental changes
      associated with metamorphosis. However, the regulation underlying the
      coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined
      the function of a homolog of the vertebrate POU domain protein, Ventral veins
      lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red
      flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated
      silencing of vvl expression led to both precocious metamorphosis and inhibition
      of molting in the larva. Ectopic application of a JH analog on vvl knockdown
      larvae delayed the onset of metamorphosis and led to a prolonged larval stage,
      indicating that Vvl acts upstream of JH signaling. Accordingly, vvl knockdown
      also reduced the expression of a JH biosynthesis gene, JH acid methyltransferase
      3 (jhamt3). In addition, ecdysone titer and the expression of the ecdysone
      response gene, hormone receptor 3 (HR3), were reduced in vvl knockdown larvae.
      The expression of the ecdysone biosynthesis gene phantom (phm) and spook (spo)
      were reduced in vvl knockdown larvae in the anterior and posterior halves,
      respectively, indicating that Vvl might influence ecdysone biosynthesis in both
      the prothoracic gland and additional endocrine sources. Injection of 20
      hydroxyecdysone (20E) into vvl knockdown larvae could restore the expression of
      HR3 although molting was never restored. These findings suggest that Vvl
      coordinates both JH and ecdysteroid biosynthesis as well as molting behavior to
      influence molting and the timing of metamorphosis. Thus, in both vertebrates and
      insects, POU factors modulate the production of major neuroendocrine regulators
      during sexual maturation. 

PMID- 24945492
TI  - A prospective observational study assessing home parenteral nutrition in patients
      with gastrointestinal cancer: benefits for quality of life.
AB  - CONTEXT: Patients with gastrointestinal cancer are at high risk for deterioration
      of nutrition. Home parenteral nutrition (HPN) could improve nutritional status
      and quality of life (QoL). OBJECTIVES: The purpose of this study was 1) to
      evaluate the impact of HPN on QoL, 2) to assess changes in nutritional status,
      and 3) to assess proxy perception of patient well-being. METHODS: We conducted a
      prospective, observational, and a multicenter study. Inclusion criteria were
      adult patients with gastrointestinal cancer, for whom HPN was indicated and
      prescribed for at least 14 days. The physician, the patient, and a family member
      completed questionnaires at inclusion and 28 days later. The QoL was assessed by
      the patients using the Functional Assessment of Cancer Therapy-General
      questionnaire, at inclusion and 28 days later. RESULTS: The study included 370
      patients with gastrointestinal cancer. The HPN was indicated for cancer-related
      undernutrition in 89% of the patients and was used as a complement to oral intake
      in 84%. After 28 days of parenteral intake, global QoL was significantly
      increased (48.9 at inclusion vs. 50.3, P=0.007). The patients' weight improved
      significantly by 2.7% (P<0.001). The nutrition risk screening also decreased
      significantly (3.2+/-1.1 vs. 2.8+/-1.3, P=0.003). CONCLUSION: HPN could provide
      benefit for malnourished patients with gastrointestinal cancer. However,
      randomized controlled studies are required to confirm this benefit and the safety
      profile.

PMID- 24945493
TI  - Effect of second cooling on the chemical components of essential oils from orange
      peel (Citrus sinensis).
AB  - A second cooling was added to the oil collectors of an improved Clevenger-type
      apparatus (ICT) to investigate the thermal reaction of essential oils from orange
      peel compared to a traditional Clevenger-type apparatus (CT). The results
      demonstrated the yield rate of essential oil from ICT was significantly higher (p
      < 0.05) than that from CT. The major components of the essential oils consisted
      of monoterpenes, such as d-limonene, beta-myrcene, beta-pinene, gamma-terpinene,
      alpha-pinene. Interestingly, ICT prevented the thermal reaction-the
      transformation of beta-myrcene to beta-thujene-and reduced the oxidation on alpha
      pinene and beta-pinene of the essential oil in comparison to CT. In addition, the
      yield rate of gamma-terpinene can also be improved via ICT compared to CT. Thus,
      ICT is an effective improvement to traditional CT. 

PMID- 24945496
TI  - International Society for Computational Biology Honors Dana Pe'er with Top
      Bioinformatics/Computational Biology Award for 2014.

PMID- 24945495
TI  - Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus
      promotes host defense with minimal impact on resistance.
AB  - Bacterial signaling systems are prime drug targets for combating the global
      health threat of antibiotic resistant bacterial infections including those caused
      by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin
      and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally
      associated with these. Whether efficacious chemical inhibitors of agr signaling
      can be developed that promote host defense against SSTIs while sparing the normal
      microbiota of the skin is unknown. In a high throughput screen, we identified a
      small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that
      disrupted agr-mediated quorum sensing in this pathogen but not in the important
      skin commensal Staphylococcus epidermidis. Mechanistic studies employing
      electrophoretic mobility shift assays and a novel AgrA activation reporter strain
      revealed the transcriptional regulator AgrA as the target of inhibition within
      the pathogen, preventing virulence gene upregulation. Consistent with its minimal
      impact on exponential phase growth, including skin microbiota members, savirin
      did not provoke stress responses or membrane dysfunction induced by conventional
      antibiotics as determined by transcriptional profiling and membrane potential and
      integrity studies. Importantly, savirin was efficacious in two murine skin
      infection models, abating tissue injury and selectively promoting clearance of
      agr+ but not Deltaagr bacteria when administered at the time of infection or
      delayed until maximal abscess development. The mechanism of enhanced host defense
      involved in part enhanced intracellular killing of agr+ but not Deltaagr in
      macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition
      of agr was not observed after multiple passages either in vivo or in vitro where
      under the same conditions resistance to growth inhibition was induced after
      passage with conventional antibiotics. Therefore, chemical inhibitors can
      selectively target AgrA in S. aureus to promote host defense while sparing agr
      signaling in S. epidermidis and limiting resistance development. 

PMID- 24945498
TI  - Molecular and Serological Intraocular Fluid Analysis of Coxiella burnetii
      seropositive Patients with Concurrent Idiopathic Uveitis.
AB  - PURPOSE: Previous studies have suggested a link between Q fever and uveitis. We
      determined whether Coxiella burnetii causes intraocular infection in C. burnetii
      seropositive patients with idiopathic uveitis. METHODS: From a retrospective
      observational case series, paired aqueous humor and serum samples from 10 C.
      burnetii-seropositive patients with idiopathic uveitis were examined for
      intraocular antibody production by using the Goldmann-Witmer coefficient and by
      polymerase chain reaction (PCR). RESULTS: Although intraocular IgG against C.
      burnetii was detected, no intraocular antibody production was observed (low
      Goldmann Wittmer coefficients). All PCR results were negative. CONCLUSIONS:
      Uveitis due to an intraocular infection with C. burnetii is unlikely.

PMID- 24945497
TI  - Induction of type I and type III interferons by Borrelia burgdorferi correlates
      with pathogenesis and requires linear plasmid 36.
AB  - The capacity for Borrelia burgdorferi to cause disseminated infection in humans
      or mice is associated with the genotype of the infecting strain. The cytokine
      profiles elicited by B. burgdorferi clinical isolates of different genotype
      (ribosomal spacer type) groups were assessed in a human PBMC co-incubation model.
      RST1 isolates, which are more frequently associated with disseminated Lyme
      disease in humans and mice, induced significantly higher levels of IFN-alpha and
      IFN-lambda1/IL29 relative to RST3 isolates, which are less frequently associated
      with disseminated infection. No differences in the protein concentrations of IFN
      gamma, IL-1beta, IL-6, IL-8, IL-10 or TNF-alpha were observed between isolates of
      differing genotype. The ability of B. burgdorferi to induce type I and type III
      IFNs was completely dependent on the presence of linear plasmid (lp) 36. An lp36
      deficient B. burgdorferi mutant adhered to, and was internalized by, PBMCs and
      specific dendritic cell (DC) subsets less efficiently than its isogenic B31
      parent strain. The association defect with mDC1s and pDCs could be restored by
      complementation of the mutant with the complete lp36. The RST1 clinical isolates
      studied were found to contain a 2.5-kB region, located in the distal one-third of
      lp36, which was not present in any of the RST3 isolates tested. This divergent
      region of lp36 may encode one or more factors required for optimal spirochetal
      recognition and the production of type I and type III IFNs by human DCs, thus
      suggesting a potential role for DCs in the pathogenesis of B. burgdorferi
      infection.

PMID- 24945499
TI  - The combination of amoxicillin-clavulanic acid and ketoconazole in the treatment
      of Madurella mycetomatis eumycetoma and Staphylococcus aureus co-infection.
AB  - Eumycetoma is a chronic progressive disabling and destructive inflammatory
      disease which is commonly caused by the fungus Madurella mycetomatis. It is
      characterized by the formation of multiple discharging sinuses. It is usually
      treated by antifungal agents but it is assumed that the therapeutic efficiency of
      these agents is reduced by the co-existence of Staphylococcus aureus co-infection
      developing in these sinuses. This prospective study was conducted to investigate
      the safety, efficacy and clinical outcome of combined antibiotic and antifungal
      therapy in eumycetoma patients with superimposed Staphylococcus aureus infection.
      The study enrolled 337 patients with confirmed M. mycetomatis eumycetoma and S.
      aureus co-infection. Patients were allocated into three groups; 142 patients
      received amoxicillin-clavulanic acid and ketoconazole, 93 patients received
      ciprofloxacin and ketoconazole and 102 patients received ketoconazole only. The
      study showed that, patients who received amoxicillin-clavulanic acid and
      ketoconazole treatment had an overall better clinical outcome compared to those
      who had combined ciprofloxacin and ketoconazole or to those who received
      ketoconazole only. In this study, 60.6% of the combined amoxicillin-clavulanic
      acid/ketoconazole group showed complete or partial clinical response to treatment
      compared to 30.1% in the ciprofloxacin/ketoconazole group and 36.3% in the
      ketoconazole only group. The study also showed that 64.5% of the patients in the
      ciprofloxacin/ketoconazole group and 59.8% in the ketoconazole only group had
      progressive disease and poor outcome. This study showed that the combination of
      amoxicillin-clavulanic acid and ketoconazole treatment is safe and offers good
      clinical outcome and it is therefore recommended to treat eumycetoma patients
      with Staphylococcus aureus co-infection. 

PMID- 24945500
TI  - Ex vivo expansion of bovine corneal endothelial cells in xeno-free medium
      supplemented with platelet releasate.
AB  - Clinical-grade ex vivo expansion of corneal endothelial cells can increase the
      availability of corneal tissues for transplantation and treatment of corneal
      blindness. However, these cells have very limited proliferative capacity.
      Successful propagation has required so far to use very complex growth media
      supplemented with fetal bovine serum and other xenocomponents. We hypothesized
      that human platelet releasates rich in multiple growth factors, and in particular
      neurotrophins, could potentially be a useful supplement for ex vivo expansion of
      corneal endothelium cells due to their neural crest origin. Platelet releasates
      were prepared by calcium salt activation of apheresis platelet concentrates,
      subjected or not to complement inactivation by heat treatment at 56 degrees C for
      30 minutes. Platelet releasates were characterized for their content in proteins
      and were found to contain high amount of growth factors including platelet
      derived growth factor-AB (30.56 to 39.08 ng/ml) and brain-derived neurotrophic
      factor (30.57 to 37.11 ng/ml) neurotrophins. We compared the growth and viability
      of corneal endothelium cells in DMEM-F12 medium supplemented with different
      combinations of components, including 2.5%~10% of the platelet releasates.
      Corneal endothelium cells expanded in platelet releasates exhibited good adhesion
      and a typical hexagonal morphology. Their growth and viability were enhanced when
      using the complement-inactivated platelet releasate at a concentration of 10%.
      Immunostaining and Western blots showed that CECs maintained the expressions of
      four important membrane markers: Na-K ATPase alpha1, zona occludens-1, phospho
      connexin 43 and N-cadherin. In conclusion, our study provides the first proof-of
      concept that human platelet releasates can be used for ex vivo expansion of
      corneal endothelium cells. These findings open a new paradigm for ex vivo
      propagation protocols of corneal endothelium cells in compliance with good tissue
      culture practices and regulatory recommendations to limit the use of xenogenic
      materials. 

PMID- 24945501
TI  - A scabies mite serpin interferes with complement-mediated neutrophil functions
      and promotes staphylococcal growth.
AB  - BACKGROUND: Scabies is a contagious skin disease caused by the parasitic mite
      Sarcoptes scabiei. The disease is highly prevalent worldwide and known to
      predispose to secondary bacterial infections, in particular by Streptococcus
      pyogenes and Staphylococcus aureus. Reports of scabies patients co-infected with
      methicillin resistant S. aureus (MRSA) pose a major concern for serious down
      stream complications. We previously reported that a range of complement
      inhibitors secreted by the mites promoted the growth of S. pyogenes. Here, we
      show that a recently characterized mite serine protease inhibitor (SMSB4)
      inhibits the complement-mediated blood killing of S. aureus.
      METHODOLOGY/PRINCIPAL FINDINGS: Blood killing of S. aureus was measured in whole
      blood bactericidal assays, counting viable bacteria recovered after treatment in
      fresh blood containing active complement and phagocytes, treated with recombinant
      SMSB4. SMSB4 inhibited the blood killing of various strains of S. aureus
      including methicillin-resistant and methicillin-sensitive isolates.
      Staphylococcal growth was promoted in a dose-dependent manner. We investigated
      the effect of SMSB4 on the complement-mediated neutrophil functions, namely
      phagocytosis, opsonization and anaphylatoxin release, by flow cytometry and in
      enzyme linked immuno sorbent assays (ELISA). SMSB4 reduced phagocytosis of S.
      aureus by neutrophils. It inhibited the deposition of C3b, C4b and properdin on
      the bacteria surface, but did not affect the depositions of C1q and MBL. SMSB4
      also inhibited C5 cleavage as indicated by a reduced C5b-9 deposition.
      CONCLUSIONS/SIGNIFICANCE: We postulate that SMSB4 interferes with the activation
      of all three complement pathways by reducing the amount of C3 convertase formed.
      We conclude that SMSB4 interferes with the complement-dependent killing function
      of neutrophils, thereby reducing opsonization, phagocytosis and further
      recruitment of neutrophils to the site of infection. As a consequence secreted
      scabies mites complement inhibitors, such as SMSB4, provide favorable conditions
      for the onset of S. aureus co-infection in the scabies-infected microenvironment
      by suppressing the immediate host immune response.

PMID- 24945504
TI  - Surgical exposure of the Distal Radius in a patient with a flexor carpi radialis
      brevis muscle anomaly.
AB  - There are numerous reports of anatomical variants of the muscles of the forearm,
      particularly the extensors of the wrist and hand. The abnormal deep and short
      radial wrist flexor (flexor carpi radialis) is rare. There are only two
      previously reported cases. We present the case of an anomalous 'flexor carpi
      radialis brevis', muscle found intra-operatively during a volar approach to the
      distal radius and discuss the strategies needed for further exposure in order to
      complete the procedure. 

PMID- 24945503
TI  - Spectroscopic properties of benzene at the air-ice interface: a combined
      experimental-computational approach.
AB  - A combined experimental and computational approach was used to study the
      spectroscopic properties of benzene at the ice-air interface at 253 and 77 K in
      comparison with its spectroscopic behavior in aqueous solutions. Benzene
      contaminated ice samples were prepared either by shock-freezing of benzene
      aqueous solutions or by benzene vapor-deposition on pure ice grains and examined
      using UV diffuse reflectance and emission spectroscopies. Neither the absorption
      nor excitation nor emission spectra provided unambiguous evidence of benzene
      associates on the ice surface even at a higher surface coverage. Only a small
      increase in the fluorescence intensity in the region above 290 nm found
      experimentally might be associated with formation of benzene excimers perturbed
      by the interaction with the ice surface as shown by ADC(2) excited-state
      calculations. The benzene associates were found by MD simulations and ground
      state DFT calculations, although not in the arrangement that corresponds to the
      excimer structures. Our experimental results clearly demonstrated that the energy
      of the S0 -> S1 electronic transition of benzene is not markedly affected by the
      phase change or the microenvironment at the ice-air interface and its absorption
      is limited to the wavelengths below 268 nm. Neither benzene interactions with the
      water molecules of ice nor the formation of dimers and microcrystals at the air
      ice interface thus causes any substantial bathochromic shift in its absorption
      spectrum. Such a critical evaluation of the photophysical properties of organic
      contaminants of snow and ice is essential for predictions and modeling of
      chemical processes occurring in polar regions. 

PMID- 24945505
TI  - A Contralateral Complication of Extra-peritoneal Laparoscopic Inguinal Hernia
      Repair.
AB  - A 63 year old female underwent an uncomplicated total extraperitoneal repair of a
      right direct inguinal hernia. One week later she presented with a strangulated
      left femoral hernia. We believe the dissection of the extraperitoneal space
      caused bleeding which tracked down through the femoral canal resulting in a
      femoral hernia. To date there are no reports of such a complication following
      total extraperitoneal inguinal hernia repair in the literature. 

PMID- 24945506
TI  - Pneumomediastinum after cocaine use: an unusual aetiology.
AB  - We describe an interesting case of pneumomediastinum secondary to cocaine abuse.
      The patient presented with severe chest pain following nasal inhalation of a
      large quantity of cocaine. Investigations revealed no chest injury; however
      oesophagitis was proven leading to a possible aetiology of oesophageal
      microperforation. After conservative management there was spontaneous resolution
      of the pneumomediastinum. 

PMID- 24945507
TI  - Necrotising soft tissue infection following mastectomy.
AB  - Necrotising fasciitis is a rare but rapidly progressive soft tissue disease which
      can lead to extensive necrosis, systemic sepsis and death. Including this case,
      only 7 other cases have been reported in the world literature with only 2 others
      affecting the patient post mastectomy. This 59 year old Caucasian lady presented
      with severe soft tissue infection soon after mastectomy, which was successfully
      treated with a combination of debridement, triangulation, VAC(c) dressing and
      skin grafting. Necrotising soft tissue infections following mastectomy are
      rapidly progressive and potentially extremely serious. It is essential that a
      high index of clinical suspicion is maintained together with prompt aggressive
      treatment in a multidisciplinary environment to prevent worsening physical and
      psychological sequelae. 

PMID- 24945508
TI  - Advanced upper eyelid sebaceous gland carcinoma with deep orbital extension.
AB  - Sebaceous gland carcinomas (SGC) are highly malignant lid tumors which originate
      from meibomian glands and rarely from the gland of Zeis, sebaceous gland of
      caruncle, eyebrows and periocular skin. In many cases correct diagnosis of SGC is
      delayed because of its ability to masquerade as a variety of other ocular
      conditions. A forty year old male presented with a left upper eyelid swelling
      with an ulcerated wound on its nasal aspect. A differential diagnosis of
      sebaceous gland carcinoma or preseptal cellulitis was made. Contrast enhanced
      computed tomography showed an ill defined soft tissue density mass in the left
      orbit encasing the whole of the optic nerve. A total exentration was performed. A
      diagnosis of meibomian gland carcinoma was confirmed on histopathology. This is a
      report of an advanced sebaceous gland carcinoma with deep orbital extension. An
      early diagnosis and appropriate treatment may decrease the long term morbidity
      and extend the survival rate of such patients. 

PMID- 24945509
TI  - Increased contact heat evoked potential stimulation latencies in responders to
      spinal cord stimulation for painful diabetic polyneuropathy.
AB  - OBJECTIVES: To analyze sensory characteristics and small nerve fiber function in
      patients suffering from painful diabetic polyneuropathy (PDP) and compare
      outcomes in responders and nonresponders to SCS treatment. METHODS: Fifteen
      patients with intractable PDP in the legs were recruited. If trial stimulation
      resulted in clinically relevant pain relief, a pulse generator was implanted and
      pain scores were measured after 12 months. Sensory characteristics (modified
      Inflammatory Neuropathy Cause and Treatment [md-INCAT] sum score) and small nerve
      fiber function (contact heat evoked potentials, CHEPs) were measured before
      implantation (D1), and CHEP measurement was repeated after two weeks of trial
      stimulation (D2). Outcomes in responders (N = 10) and nonresponders (N = 5) to
      SCS treatment were compared. Data were analyzed using nonparametric statistics.
      RESULTS: At one year, clinically relevant pain relief was achieved in 10 out of
      15 patients. The md-INCAT score did not differ between SCS responders and
      nonresponders (8.0 vs. 5.0; p = 0.59). No differences were found in CHEP outcomes
      at D1 vs. D2, except for dorsal forearm P2 latency, and the correlation between
      D1 and D2 CHEP outcomes was high. Volar N2 forearm latency (0.492 vs. 0.434; p <
      0.01), dorsal forearm N2 latency (0.518 vs. 0.453; p = 0.04), and dorsal forearm
      P2 latency (0.660 vs. 0.589; p = 0.04) were increased in SCS responders as
      compared with SCS nonresponders. CONCLUSIONS: From this small-scale clinical
      pilot study we conclude that forearm CHEP latencies are increased in PDP patients
      who respond to SCS therapy as compared with SCS nonresponders. Before the CHEP
      latency can be used as a predictor of SCS outcome in PDP patients, a large-scale
      study is needed.

PMID- 24945512
TI  - Error of the method: what is it for?

PMID- 24945511
TI  - Reasons for mini-implants failure: choosing installation site should be valued!
AB  - Mini-implant loss is often associated with physical and mechanical aspects that
      result from choosing an inappropriate placement site. It is worth highlighting
      that: a) Interdental alveolar bone crests are flexible and deformable. For this
      reason, they may not offer the ideal absolute anchorage. The more cervical the
      structures, the more delicate they are, thus offering less physical support for
      mini-implant placement; b) Alveolar bone crests with triangular shape are more
      deformable, whereas those with rectangular shape are more flexible; c) The bases
      of the alveolar processes of the maxilla and the mandible are not flexible, for
      this reason, they are more likely to receive mini-implants; d) The more cervical
      a mini-implant is placed, the higher the risk of loss; the more apical a mini
      implant is placed, the better its prognosis will be; e) 3D evaluations play a
      major role in planning the use of mini-implants. Based on the aforementioned
      considerations, the hypotheses about mini-implant loss are the following: 1)
      Deflection of maxillary and mandibular alveolar processes when mini-implants are
      more cervically placed; 2) Mini-implants placed too near the periodontal
      ligament, with normal intra-alveolar tooth movement; 3) Low bone density, low
      thickness and low alveolar bone volume; 4) Decreased alveolar cortical bone
      thickness; 5) Excessive pressure inducing trabecular bone microfracture; 6) Sites
      with higher anatomical weakness in the mandible and the maxilla; 7) Thicker
      gingival tissue not considered when choosing the mini-implant.

PMID- 24945510
TI  - 2012-2013 Seasonal influenza vaccine effectiveness against influenza
      hospitalizations: results from the global influenza hospital surveillance
      network.
AB  - BACKGROUND: The effectiveness of currently licensed vaccines against influenza
      has not been clearly established, especially among individuals at increased risk
      for complications from influenza. We used a test-negative approach to estimate
      influenza vaccine effectiveness (IVE) against hospitalization with laboratory
      confirmed influenza based on data collected from the Global Influenza Hospital
      Surveillance Network (GIHSN). METHODS AND FINDINGS: This was a multi-center,
      prospective, active surveillance, hospital-based epidemiological study during the
      2012-2013 influenza season. Data were collected from hospitals participating in
      the GIHSN, including five in Spain, five in France, and four in the Russian
      Federation. Influenza was confirmed by reverse transcription-polymerase chain
      reaction. IVE against hospitalization for laboratory-confirmed influenza was
      estimated for adult patients targeted for vaccination and who were swabbed within
      7 days of symptom onset. The overall adjusted IVE was 33% (95% confidence
      interval [CI], 11% to 49%). Point estimates of IVE were 23% (95% CI, -26% to 53%)
      for influenza A(H1N1)pdm09, 30% (95% CI, -37% to 64%) for influenza A(H3N2), and
      43% (95% CI, 17% to 60%) for influenza B/Yamagata. IVE estimates were similar in
      subjects <65 and >=65 years of age (35% [95% CI, -15% to 63%] vs.31% [95% CI, 4%
      to 51%]). Heterogeneity in site-specific IVE estimates was high (I2 = 63.4%) for
      A(H1N1)pdm09 in patients >=65 years of age. IVE estimates for influenza
      B/Yamagata were homogenous (I2 = 0.0%). CONCLUSIONS: These results, which were
      based on data collected from the GIHSN during the 2012-2013 influenza season,
      showed that influenza vaccines provided low to moderate protection against
      hospital admission with laboratory-confirmed influenza in adults targeted for
      influenza vaccination. In this population, IVE estimates against A(H1N1)pdm09
      were sensitive to age group and study site. Influenza vaccination was moderately
      effective in preventing admissions with influenza B/Yamagata for all sites and
      age groups.

PMID- 24945513
TI  - Transverse effect of Haas and Hyrax appliances on the upper dental arch in
      patients with unilateral complete cleft lip and palate: a comparative study.
AB  - OBJECTIVE: The aim of the present study was to evaluate the transverse effect of
      rapid maxillary expansion in patients with unilateral complete cleft lip and
      palate while comparing the Haas and Hyrax appliances. METHODS: The sample
      consisted of 48 patients divided into two groups: Group I = 25 patients treated
      with modified Haas appliance (mean age: 10 years and 8 months); and Group II = 23
      patients treated with Hyrax appliance (mean age: 10 years and 6 months). Cast
      models were taken during pre-expansion and after removal of the appliance, at the
      end of the retention period. The models were scanned with the aid of the 3 Shape
      R700 3D scanner. Initial and final transverse distances were measured at cusp
      tips and cervical-palatal points of maxillary teeth by using the Ortho Analyzer
      3D software. RESULTS: The mean expansion obtained between cusp tips and between
      cervical-palatal points was, respectively: for inter-canine width, 4.80 mm and
      4.35 mm with the Haas appliance and 5.91 mm and 5.91 mm with the Hyrax appliance;
      as for first deciduous molars or first deciduous premolars, the values obtained
      were 6.46 mm and 5.90 mm in the Haas group, and 7.11 mm and 6.65 mm in the Hyrax
      group; with regard to first molars, values were 6.11 mm and 5.24 mm in the Haas
      group, and 7.55 mm and 6.31 mm in the Hyrax group. CONCLUSION: Rapid maxillary
      expansion significantly increased the transverse dimensions of the upper dental
      arch in patients with cleft palate, with no significant differences between the
      Hass and Hyrax expanders.

PMID- 24945514
TI  - The influence of orthodontic fixed appliances on the oral microbiota: a
      systematic review.
AB  - OBJECTIVE: To investigate whether there is scientific evidence to support the
      hypothesis that the presence of orthodontic fixed appliances influences the oral
      microbiota. METHODS: The search for articles was conducted in PubMed; ISI Web of
      Knowledge and Ovid databases, including articles published in English until May
      17th, 2012. They should report human observational studies presenting the
      following keywords: "fixed orthodontic appliance" AND "microbiological
      colonization"; OR "periodontal pathogens"; OR "Streptococcus"; OR
      "Lactobacillus"; OR "Candida"; OR "Tannerella forsythia"; OR "Treponema
      denticola"; OR "Fusobacterium nucleatum"; OR "Actimomyces actinomycetemcomitans";
      OR "Prevotella intermedia"; OR "Prevotella nigrescens"; OR "Porphyromonas
      gingivalis". Articles were previously selected by title and abstract. Articles
      that met the inclusion criteria were analyzed and classified as having low,
      moderate or high methodology quality. A new detailed checklist for quality
      assessment was developed based on the information required for applicable data
      extraction for reviews. The study design, sample, follow-up period, collection
      and microbial analysis methods, statistical treatment, results and discussion
      were assessed. RESULTS: The initial search retrieved 305 articles of which 33
      articles were selected by title and abstract. After full-text reading, 8 articles
      met the inclusion criteria, out of which 4 articles were classified as having low
      and 4 as moderate methodological quality. The moderate methodological quality
      studies were included in the systematic review. CONCLUSIONS: The literature
      revealed moderate evidence that the presence of fixed appliances influences the
      quantity and quality of oral microbiota.

PMID- 24945515
TI  - Bibliometric analysis of scientific articles published in Brazilian and
      international orthodontic journals over a 10-year period.
AB  - OBJECTIVE: This study aimed at describing the profiles of Brazilian and
      international studies published in orthodontic journals. METHODS: The sample
      comprised 635 articles selected from two scientific journals, i.e., Dental Press
      Journal of Orthodontics and American Journal of Orthodontics and Dentofacial
      Orthopedics, which were analyzed at three different intervals over a 10-year
      period (1999 - 2004 - 2009). Articles were described in terms of knowledge
      domain, study design, and country of origin (or state of origin for Brazilian
      papers). RESULTS: The most frequent study designs adopted in international
      studies were cohort (23.9%) and cross-sectional (21.7%) designs. Among Brazilian
      papers, cross-sectional studies (28.9%) and literature reviews (24.6%) showed
      greater frequency. The topics most often investigated in international articles
      were dental materials (17%) and treatment devices (12.4%), with the latter topic
      being addressed by 16% of the Brazilian publications, followed by malocclusion,
      with 12.6%. In all cases, the most frequent countries of origin coincided with
      the countries of origin of each journal. CONCLUSIONS: The majority of the studies
      analyzed featured a low level of scientific evidence. Moreover, the findings
      showed that journals tend to publish studies produced in their own country of
      origin, and that there are marked discrepancies in the number of papers published
      by different Brazilian states.

PMID- 24945516
TI  - Photometric analysis of esthetically pleasant and unpleasant facial profile.
AB  - OBJECTIVE: To identify which linear, angular and proportionality measures could
      influence a profile to be considered esthetically pleasant or unpleasant, and to
      assess sexual dimorphism. METHODS: 150 standardized facial profile photographs of
      dental students of both sexes were obtained and printed on photographic paper.
      Ten plastic surgeons, ten orthodontists and ten layperson answered a
      questionnaire characterizing each profile as pleasant, acceptable or unpleasant.
      With the use of a score system, the 15 most pleasant and unpleasant profiles of
      each sex were selected. The photographs were scanned into AutoCAD computer
      software. Linear, angular and proportion measurements were obtained using the
      software tools. The average values between groups were compared by the Student's
      t-test and the Mann-Whitney test at a significance level of 5%. RESULTS: The
      linear measures LL-S, LL-H, LL-E, LL-B and Pn-H showed statistically significant
      differences (p < 0.05). Statistical differences were also found in the angular
      measures G'.Pn.Pg', G'.Sn.Pg' and Sn.Me'.C and in the proportions G'-Sn:Sn-Me'
      and Sn-Gn':Gn'-C (p < 0.05). Differences between sexes were found for the linear
      measure Ala-Pn, angles G'-Pg'.N-Pn, Sn.Me'.C, and proportions Gn'-Sn:Sn-Me' and
      Ala-Pn:N'-Sn. (p < 0.05). CONCLUSION: The anteroposterior position of the lower
      lip, the amount of nose that influences the profile, facial convexity, total
      vertical proportion and lip-chin proportion appear to influence pleasantness of
      facial profile. Sexual dimorphism was identified in nasal length, nasofacial and
      lower third of the face angles, total vertical and nasal height/length
      proportions.

PMID- 24945517
TI  - Comparison of topical and infiltration anesthesia for orthodontic mini-implant
      placement.
AB  - OBJECTIVE: To compare the acceptability and effectiveness of topical and
      infiltration anesthesia for placement of mini-implants used as temporary
      anchorage devices. METHODS: The sample comprised 40 patients, 17 males and 23
      females, whose mean age was of 26 years and who were all undergoing orthodontic
      treatment and in need for anchorage reinforcement. Mini-implants were bilaterally
      placed in the maxilla of all individuals, with infiltration anesthesia on one
      side and topical anesthesia on the other. These 40 patients completed two
      questionnaires, one before and another after mini-implant placement, and pain was
      measured through a visual analog scale (VAS). The data collected were analyzed
      using descriptive statistics and the measurements of pain were compared by means
      of Mann-Whitney non-parametric test. RESULTS: It was found that 60% of patients
      felt more comfortable with the use of topical anesthesia for mini-implant
      placement; 72.5% of patients described the presence of pressure during placement
      of the anchorage device as the most unpleasant sensation of the entire process;
      62.5% of patients felt more pain with the use of topical anesthesia. CONCLUSION:
      It was concluded that patients had less pain with the use of infiltration
      anesthesia, and also preferred this type of anesthetic.

PMID- 24945518
TI  - Evaluation of a photographic method to measure dental angulation.
AB  - OBJECTIVE: To analyze the reliability and reproducibility of a simplified method
      for analysis of dental angulation using digital photos of plaster dental casts.
      METHODS: Digital and standardized photographs of plaster casts were performed and
      posteriorly imported to an angle reading graphic program in order to have
      measurements obtained. Such procedures were repeated to evaluate the random error
      and to analyze reproducibility through intraclass correlation. The sample
      consisted of 12 individuals (6 male and 6 female) with full permanent dentition
      and not orthodontically treated. The analyses were bilaterally carried out, and
      generated 24 measurements. RESULTS: The random error showed variation of 0.77 to
      2.55 degrees for teeth angulation. The statistical analysis revealed that the
      method presents excellent reproducibility (p < 0.0001) for all teeth, except for
      the upper premolars. In spite of that, it is still considered statistically
      significant (p < 0.001). CONCLUSION: The proposed method presents enough
      reliability that justifies its use in the development of scientific research as
      well as in clinical practice.

PMID- 24945519
TI  - Reliability of CBCT in the diagnosis of dental asymmetry.
AB  - OBJECTIVE: The aim of this study was to validate a method used to assess dental
      asymmetry, in relation to the skeletal midline, by means of CBCT. METHODS: Ten
      patients who had CBCT scans taken were randomly selected for this study. Five
      different observers repeated 10 landmarks (x, y and z variables for each) and 12
      linear measurements within 10 days. Measurements were taken in both arches to
      evaluate symmetry of first molars, canines and dental midline in relation to the
      skeletal midline. Intraclass correlation coefficient (ICC) was carried out to
      assess intra- and interobserver reliability for landmarks and distances. Average
      mean difference was also assessed to check measurement errors between observers.
      RESULTS: ICC for the landmarks was, respectively, >= 0.9 for 27 (90%) and 25
      (83%) variables for intra- and interobserver; ICC for distances was >= 0.9 for 7
      (58%) and 5 (42%), respectively. All ICC landmarks for distances were >0.75 for
      both intra- and interobserver. The mean difference between observers was <= 0.6
      mm for all the distances. CONCLUSION: The method used to assess dental asymmetry
      by means of CBCT is valid. Measurements of molars, canines and dental midline
      symmetry with the skeletal midline are reproducible and reliable when taken by
      means of CBCT and by different operators.

PMID- 24945520
TI  - Nicotine effect on bone remodeling during orthodontic tooth movement:
      histological study in rats.
AB  - INTRODUCTION: Nicotine is harmful to angiogenesis, osteogenesis and synthesis of
      collagen. OBJECTIVE: The aim of this study was to investigate the effect of
      nicotine on bone remodeling during orthodontic movement in rats. METHODS: Eighty
      male Wistar rats were randomly divided into three groups: Group C (control),
      group CM (with orthodontic movement) and group NM (nicotine with orthodontic
      movement) groups. The animals comprising groups C and CM received 0.9% saline
      solution while group NM received nicotine solution (2 mg/kg). A nickel-titanium
      closed-coil spring was used to induce tooth movement. The animals were euthanized
      and tissue specimens were histologically processed. Blood vessels, Howship's
      lacunae and osteoclast-like cells present in the tension and compression areas of
      periodontal ligaments were quantified. The extent of bone formation was evaluated
      under polarized light, to determine the percentage of immature/mature collagen.
      RESULTS: It was observed lower blood vessel densities in the NM group in
      comparison to the CM group, three (p < 0.001) and seven (p < 0.05) days after
      force application. Osteoclast-like cells and Howship's lacunae in the NM group
      presented lower levels of expression, in comparison to the CM group, with
      significant differences on day 7 (p < 0.05 for both variables) and day 14 (p <
      0.05 for osteoclast-like cells and p < 0.01 for Howship's lacunae). The
      percentage of immature collagen was increased in the NM group in comparison to
      the CM group, with a statistically significant difference on day 3 (p < 0.05),
      day 7 (p < 0.001), day 14 (p < 0.001) and day 21 (p < 0.001). CONCLUSIONS:
      Nicotine affects bone remodeling during orthodontic movement, reducing
      angiogenesis, osteoclast-like cells and Howship's lacunae, thereby delaying the
      collagen maturation process in new bone matrix.

PMID- 24945521
TI  - Corrosion behavior of self-ligating and conventional metal brackets.
AB  - OBJECTIVE: To test the null hypothesis that the aging process in self-ligating
      brackets is not higher than in conventional brackets. METHODS: Twenty-five
      conventional (GN-3M/Unitek; GE-GAC; VE-Aditek) and 25 self-ligating (SCs
      3M/Unitek; INs-GAC; ECs-Aditek) metal brackets from three manufacturers (n = 150)
      were submitted to aging process in 0.9% NaCl solution at a constant temperature
      of 37 +/- 1 degrees C for 21 days. The content of nickel, chromium and iron ions
      in the solution collected at intervals of 7, 14 and 21 days was quantified by
      atomic absorption spectrophotometry. After the aging process, the brackets were
      analyzed by scanning electron microscopy (SEM) under 22X and 1,000X
      magnifications. RESULTS: Comparison of metal release in self-ligating and
      conventional brackets from the same manufacturer proved that the SCs group
      released more nickel (p < 0.05) than the GN group after 7 and 14 days, but less
      chromium (p < 0.05) after 14 days and less iron (p < 0.05) at the three
      experimental time intervals. The INs group released less iron (p < 0.05) than the
      GE group after 7 days and less nickel, chromium and iron (p < 0.05) after 14 and
      21 days. The ECs group released more nickel, chromium and iron (p < 0.05) than
      the VE group after 14 days, but released less nickel and chromium (p < 0.05)
      after 7 days and less chromium and iron (p < 0.05) after 21 days. The SEM
      analysis revealed alterations on surface topography of conventional and self
      ligating brackets. CONCLUSIONS: The aging process in self-ligating brackets was
      not greater than in conventional brackets from the same manufacturer. The null
      hypothesis was accepted.

PMID- 24945522
TI  - Class I malocclusion with anterior crossbite and severe crowding.
AB  - This article reports the orthodontic diagnosis and treatment planning carried out
      with a 14-year and 5-month-old female patient with esthetic and functional
      complaints. She presented an Angle Class I malocclusion, anterior crossbite and
      severe crowding in both maxillary and mandibular arches, in addition to a lightly
      concave straight facial profile. Orthodontic treatment did not require
      extraction. Crossbite was corrected by protrusion of upper teeth, which
      contributed to alignment and leveling of teeth, in addition to improving the
      patient's facial profile. The case was presented to the Brazilian Board of
      Orthodontics and Dentofacial Orthopedics (BBO) as a requirement for the BBO
      certification.

PMID- 24945523
TI  - Segmented arch or continuous arch technique? A rational approach.
AB  - This study aims at revising the biomechanical principles of the segmented
      archwire technique as well as describing the clinical conditions in which the
      rational use of scientific biomechanics is essential to optimize orthodontic
      treatment and reduce the side effects produced by the straight wire technique.

PMID- 24945524
TI  - Skeletal myogenic differentiation of human urine-derived cells as a potential
      source for skeletal muscle regeneration.
AB  - Stem cells are regarded as possible cell therapy candidates for skeletal muscle
      regeneration. However, invasive harvesting of those cells can cause potential
      harvest-site morbidity. The goal of this study was to assess whether human urine
      derived stem cells (USCs), obtained through non-invasive procedures, can
      differentiate into skeletal muscle linage cells (Sk-MCs) and potentially be used
      for skeletal muscle regeneration. In this study, USCs were harvested from six
      healthy individuals aged 25-55. Expression profiles of cell-surface markers were
      assessed by flow cytometry. To optimize the myogenic differentiation medium, we
      selected two from four different types of myogenic differentiation media to
      induce the USCs. Differentiated USCs were identified with myogenic markers by
      gene and protein expression. USCs were implanted into the tibialis anterior
      muscles of nude mice for 1 month. The results showed that USCs displayed surface
      markers with positive staining for CD24, CD29, CD44, CD73, CD90, CD105, CD117,
      CD133, CD146, SSEA-4 and STRO-1, and negative staining for CD14, CD31, CD34 and
      CD45. After myogenic differentiation, a change in morphology was observed from
      'rice-grain'-like cells to spindle-shaped cells. The USCs expressed specific Sk
      MC transcripts and protein markers (myf5, myoD, myosin, and desmin) after being
      induced with different myogenic culture media. Implanted cells expressed Sk-MC
      markers stably in vivo. Our findings suggest that USCs are able to differentiate
      into the Sk-MC lineage in vitro and after being implanted in vivo. Thus, they
      might be a potential source for cell injection therapy in the use of skeletal
      muscle regeneration. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24945525
TI  - Antibody array in a multiwell plate format for the sensitive and multiplexed
      detection of important plant pathogens.
AB  - The global seed market is considered to be an important industry with a total
      value of $10,543 million US dollars in 2012. Because plant pathogens such as
      bacteria and viruses cause a significant economic loss to both producers and
      exporters, the seed export industry urgently requires rapid, sensitive, and
      inexpensive testing for the pathogens to prevent disease spreading worldwide.
      This study developed an antibody array in a multiwell plate format to
      simultaneously detect four crucial plant pathogens, namely, a bacterial fruit
      blotch bacterium Acidovorax avenae subsp. citrulli (Aac), Chilli veinal mottle
      virus (ChiVMV, potyvirus), Watermelon silver mottle virus (WSMoV, tospovirus
      serogroup IV), and Melon yellow spot virus (MYSV, tospovirus). The capture
      antibodies specific to the pathogens were immobilized on each well at preassigned
      positions by an automatic microarrayer. The antibodies on the arrays specifically
      captured the corresponding pathogens present in the sample extracts. The presence
      of pathogens bound on the capture antibodies was subsequently detected by a
      cocktail of fluorescently conjugated secondary antibodies. The limits of
      detection of the developed antibody array for the detection of Aac, ChiVMV,
      WSMoV, and MYSV were 5 * 10(5) CFU/mL, 30 ng/mL, 1000 ng/mL, and 160 ng/mL,
      respectively, which were very similar to those of the conventional ELISA method.
      The antibody array in a multiwell plate format accurately detected plant
      pathogens in single and multiple detections. Moreover, this format enables easy
      handling of the assay at a higher speed of operation. 

PMID- 24945526
TI  - Fluid or fuel? The context of consuming a beverage is important for satiety.
AB  - Energy-containing beverages have a weak effect on satiety, limited by their fluid
      characteristics and perhaps because they are not considered 'food'. This study
      investigated whether the context of consuming a beverage can influence the
      satiating power of its nutrients. Eighty participants consumed a lower- (LE, 75
      kcal) and higher-energy (HE, 272 kcal) version of a beverage (covertly
      manipulated within-groups) on two test days, in one of four beverage contexts
      (between-groups): thin versions of the test-drinks were consumed as a thirst
      quenching drink (n = 20), a filling snack (n = 20), or without additional
      information (n = 20). A fourth group consumed subtly thicker versions of the
      beverages without additional information (n = 20). Lunch intake 60 minutes later
      depended on the beverage context and energy content (p = 0.030): participants who
      consumed the thin beverages without additional information ate a similar amount
      of lunch after the LE and HE versions (LE = 475 kcal, HE = 464 kcal; p = 0.690)
      as did those participants who believed the beverages were designed to quench
      thirst (LE = 442 kcal, HE = 402 kcal; p = 0.213), despite consuming an additional
      197 kcal in the HE beverage. Consuming the beverage as a filling snack led
      participants to consume less at lunch after the HE beverage compared to the LE
      version (LE = 506 kcal, HE = 437 kcal; p = 0.025). This effect was also seen when
      the beverages were subtly thicker, with participants in this group displaying the
      largest response to the beverage's energy content, consuming less at lunch after
      the HE version (LE = 552 kcal, HE = 415 kcal; p<0.001). These data indicate that
      beliefs about the consequences of consuming a beverage can affect the impact of
      its nutrients on appetite regulation and provide further evidence that a
      beverage's sensory characteristics can limit its satiating power.

PMID- 24945529
TI  - Photoreceptor replacement therapy: challenges presented by the diseased recipient
      retinal environment.
AB  - Vision loss caused by the death of photoreceptors is the leading cause of
      irreversible blindness in the developed world. Rapid advances in stem cell
      biology and techniques in cell transplantation have made photoreceptor
      replacement by transplantation a very plausible therapeutic strategy. These
      advances include the demonstration of restoration of vision following
      photoreceptor transplantation and the generation of transplantable populations of
      donor cells from stem cells. In this review, we present a brief overview of the
      recent progress in photoreceptor transplantation. We then consider in more detail
      some of the challenges presented by the degenerating retinal environment that
      must play host to these transplanted cells, how these may influence transplanted
      photoreceptor cell integration and survival, and some of the progress in
      developing strategies to circumnavigate these issues. 

PMID- 24945527
TI  - Ubiquitin-mediated response to microsporidia and virus infection in C. elegans.
AB  - Microsporidia comprise a phylum of over 1400 species of obligate intracellular
      pathogens that can infect almost all animals, but little is known about the host
      response to these parasites. Here we use the whole-animal host C. elegans to show
      an in vivo role for ubiquitin-mediated response to the microsporidian species
      Nematocida parisii, as well to the Orsay virus, another natural intracellular
      pathogen of C. elegans. We analyze gene expression of C. elegans in response to
      N. parisii, and find that it is similar to response to viral infection. Notably,
      we find an upregulation of SCF ubiquitin ligase components, such as the cullin
      ortholog cul-6, which we show is important for ubiquitin targeting of N. parisii
      cells in the intestine. We show that ubiquitylation components, the proteasome,
      and the autophagy pathway are all important for defense against N. parisii
      infection. We also find that SCF ligase components like cul-6 promote defense
      against viral infection, where they have a more robust role than against N.
      parisii infection. This difference may be due to suppression of the host
      ubiquitylation system by N. parisii: when N. parisii is crippled by anti
      microsporidia drugs, the host can more effectively target pathogen cells for
      ubiquitylation. Intriguingly, inhibition of the ubiquitin-proteasome system (UPS)
      increases expression of infection-upregulated SCF ligase components, indicating
      that a trigger for transcriptional response to intracellular infection by N.
      parisii and virus may be perturbation of the UPS. Altogether, our results
      demonstrate an in vivo role for ubiquitin-mediated defense against microsporidian
      and viral infections in C. elegans. 

PMID- 24945528
TI  - The volatile anesthetic isoflurane increases endothelial adenosine generation via
      microparticle ecto-5'-nucleotidase (CD73) release.
AB  - Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane
      is a widely used halogenated volatile anesthetic during the perioperative period
      and protects against endothelial cell death and inflammation. In this study, we
      tested whether isoflurane induces endothelial ecto-5'-nucleotidase (CD73) and
      cytoprotective adenosine generation to protect against endothelial cell injury.
      Clinically relevant concentrations of isoflurane induced CD73 activity and
      increased adenosine generation in cultured human umbilical vein or mouse
      glomerular endothelial cells. Surprisingly, isoflurane-mediated induction of
      endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73.
      We determined that isoflurane rapidly increased CD73 containing endothelial
      microparticles into the cell culture media. Indeed, microparticles isolated from
      isoflurane-treated endothelial cells had significantly higher CD73 activity as
      well as increased CD73 protein. In vivo, plasma from mice anesthetized with
      isoflurane had significantly higher endothelial cell-derived CD144+ CD73+
      microparticles and had increased microparticle CD73 activity compared to plasma
      from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in
      isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP)
      prevented isoflurane-induced protection against human endothelial cell
      inflammation and apoptosis. In addition, isoflurane activated endothelial cells
      Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light
      chain phosphorylation. Furthermore, isoflurane-induced release of CD73 containing
      microparticles was significantly attenuated by a selective Rho kinase inhibitor
      (Y27632). Taken together, we conclude that the volatile anesthetic isoflurane
      causes Rho kinase-mediated release of endothelial microparticles containing
      preformed CD73 and increase adenosine generation to protect against endothelial
      apoptosis and inflammation. 

PMID- 24945531
TI  - [Programmed cell death in cancer cells].
AB  - Resistance to programmed cell death is one of the hallmarks of cancer cells that
      affects the process of malignant transformation as well as response to cancer
      therapy. The goal of this review is to summarize recent information about
      programmed cell death (PCD) in healthy and cancer cells, as well as new
      perspectives for anticancer treatments targeting these signaling pathways. Three
      main types of PCD are described in detail: apoptosis, necrosis/ necroptosis and
      cell death associated with autophagy. Among them, apoptosis plays the key role in
      both malignant transformation and response to therapy. In this review, we
      describe main signaling pathways and molecules participating in apoptosis
      regulation in healthy cells. In most cancer cells, mutations or aberrant
      expression of proteins directly or indirectly involved in induction and execution
      of cell death can be detected -  p53, Bcl 2 family proteins, inhibitors of
      apoptosis, death receptors/ ligands and other proteins. Mutations or changes in
      expression of these proteins and their relation to certain types of tumors are
      described. Finally, we provide a review of recently developed treatments that
      target and reactivate the machinery of programmed cell death and are currently
      tested in clinical trials.

PMID- 24945530
TI  - Rapid molecular identification of human taeniid cestodes by pyrosequencing
      approach.
AB  - Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in
      humans. The difficulty of morphological identification of human taeniids can lead
      to misdiagnosis or confusion. To overcome this problem, several molecular methods
      have been developed, but use of these tends to be time-consuming. Here, a rapid
      and high-throughput pyrosequencing approach was developed for the identification
      of three human taeniids originating from various countries. Primers targeting the
      mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia
      species were designed. Variations in a 26-nucleotide target region were used for
      identification. The reproducibility and accuracy of the pyrosequencing technology
      was confirmed by Sanger sequencing. This technique will be a valuable tool to
      distinguish between sympatric human taeniids that occur in Thailand, Asia and
      Pacific countries. This method could potentially be used for the molecular
      identification of the taeniid species that might be associated with suspicious
      cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse.

PMID- 24945532
TI  - [The use of flow cytometry for analysis of the mitochondrial cell death].
AB  - Apoptosis is type I programmed cell death, a process that is essential for
      development and tissue homeostasis. It is a prevalent form of cell death and it
      proceeds via two signaling pathways - external (receptor pathway) triggered by
      death receptors and intrinsic (mitochondrial) apoptotic pathway with major
      involvement of mitochondria. Mitochondria are important cellular organelles
      producing energy stored in molecules of adenosine triphosphate that are essential
      for cell survival. The mitochondrial cell death is characterized by
      permeabilization of the mitochondrial outer membrane and dissipation of the
      transmembrane potential. Mitochondria are electronegative organelles and
      depolarization of the mitochondrial membrane is important for the release of
      proapoptotic signals. Aberrant control of the mitochondrial cell death might
      contribute to several diseases including cancer. Mitochondria are also a source
      of reactive oxygen species, Ca2+ ions and other proteins that affect processes
      important for the initiation and progression of tumors independently of
      apoptosis. Current studies focus on research of mitochondrial membrane potential
      and reactive oxygen species modulating various signaling pathways within the
      cell, their importance in carcinogenesis, and in treatment of oncological
      patients. Monitoring of the apoptotic markers, such as the mitochondrial membrane
      potential (MMP), and the level of reactive oxygen species in samples of
      oncological patients has a predictive value for the output of treatment
      protocols.

PMID- 24945533
TI  - [Methods for studying tumor cell migration and invasiveness].
AB  - Migration and invasiveness are phenotypic characteristics of cells that
      contribute to physiological processes, such as wound healing or embryogenesis and
      they are involved in serious pathological processes, namely in tumor cell
      metastasis. Availability of methods for studying migration and invasiveness of
      the cells is important for understanding molecular basis of these processes. In
      the case of cancer, migration, invasiveness and metastatic potential of tumor
      cells are key factors that determine clinical prognosis of the patients. This
      communication provides an overview of in vitro and in vivo methods which are used
      to study cell migration, invasion and metastasis. In vitro meth-ods for studying
      cell migration include simple two dimensional assays (scratch -  wound assay and
      the assay based on the effect of hepatocyte growth factor) and methods based on
      chemotaxis (Dunns chamber, videomicroscopy of cells, the use of carriers with
      chemoattractants). Methods for studying both cell migration and invasiveness in
      vitro include more complex systems based on the principle of the Boyden chamber
      (transwell migration/ invasive test, analysis of cell migration and invasion in
      xCELLigence system, confocal microscopy based approaches) as well as analysis of
      cell migration in microchannels. Our overview of in vivo methods provides an
      introduction into model organisms and methods used in this field, with an
      emphasis on the study of cancer metastasis in mouse models. The methods described
      in this review are mainly involved in larger research projects aiming at
      developing new diagnostic and therapeutic approaches in oncology.

PMID- 24945534
TI  - [Techniques to study transendothelial migration in vitro].
AB  - The most dangerous aspect of cancer is the metastatic spread to other parts of
      the body. Cancer cells frequently use circulation to spread to secondary
      locations. By entering the blood-stream (in a process called intravasation) and
      by crossing the vessel walls at the metastatic sites (extravasation) tumor cells
      disseminate to distal organs and eventually form life  threatening metastases.
      Crossing the vessel walls (transendothelial migration) is a vital step of
      metastatic cascade and the elucidation of mechanisms involved in transendothelial
      migration might inspire new strategies of targeted antimetastatic therapy. There
      are several methods to study transendothelial migration in living models (in
      vivo). Although they offer complex physiological microenvironment, they are
      expensive and technically demanding, therefore not widely used. As an
      alternative, sophisticated techniques to investigate transendothelial migration
      in vitro have been developed. They are generally more available and feasible, but
      there is still considerable variability in the difficulty of performance, the
      requirements for specialized devices, accuracy of in vivo simulation and
      relevance for oncological applications. The classification, various
      modifications, pros and cons of in vitro techniques for studying transendothelial
      migration are summarized in this review.

PMID- 24945535
TI  - [Mechanisms of drug resistance and cancer stem cells].
AB  - Although the success of anticancer treatments has been increasing annually, drug
      resistance remains the dominant cause of death of cancer patients. Initial
      therapy often leaves residual dis-ease that leads to repeated tumor development
      or to loss of its sensitivity to available therapy. One reason of residual
      disease formation is the presence of cancer stem cells (CSCs). CSCs have been
      identified as a small population of cells that is capable of self  renewal and
      differentiation. It is supposed that these cells are responsible for cancer
      initiation, progression, metastasis, recurrence and drug resistance. Over the
      past years, much attention has been paid to development of CSCs related therapies
      and to identification of key molecules involved in controlling the specific
      properties of CSCs populations. This article reviews the basic mechanisms of drug
      resistance in relation to cancer stem cells.

PMID- 24945536
TI  - [Functional assays for detection of cancer stem cells].
AB  - Cancer stem cells (CSCs) are considered to be a population of tumor cells, which
      are responsible for tumor initiation and progression. They are also involved in
      metastasizing and may be a possible cause of multidrug resistance and tumor
      recurrence. CSCs possess the ability to self  renew and show a tumorigenic
      potential. Functional assays, which enable the detection of these properties,
      represent the main tool for identification of CSCs. This article summarizes both
      in vitro and in vivo methods used to identify the CSCs with emphasis on recently
      employed techniques of CSCs detection. In vivo tumorigenicity assay, sphere
      formation assay and colony  forming unit assay belong to the most commonly used
      functional assays. Further, label  retention assay and aldehyde dehydrogenase
      activity assay are described in this article.

PMID- 24945537
TI  - [Tumor microenvironment -  possibilities of the research under in vitro
      conditions].
AB  - Tumorigenesis is always accompanied by alterations of the microenvironment in the
      respective tissue. The tumor microenvironment represents a heterogeneous complex,
      in which cell proliferation, differentiation, necrosis or apoptosis are regulated
      by various extracellular stimuli, and it can also lead to development of an
      aggressive phenotype of tumor cells. Influence of tumor microenvironment is also
      often connected with resistance to frequently used therapeutic procedures.
      Specifics of the tumor microenvironment are closely associated with the
      structural and functional abnormalities of tumor microvessels and altered
      cellular metabolism. Moreover, changes such as increase in glycolysis, elevated
      glucose uptake, production of lactate and CO2, and presence of hypoxic regions
      and regions with acidic pH are typical features of tumor tissues. At present,
      there is a lot of methods for in vitro simulation and investigation of some of
      these specific conditions, and a number of new methods are being developed. A
      detailed understanding of the specifics of the tumor microenvironment should
      increasingly improve the development of new treatment possibilities of human
      cancers.

PMID- 24945538
TI  - [Electrochemical analysis of nucleic acids, proteins and polysaccharides in
      biomedicine].
AB  - Electrochemical analysis of nucleic acids, proteins and polysaccharides
      represents an interesting, although not widely spread alternative to current
      methods based predominantly on optical detection because it offers a relatively
      inexpensive, fast and instrumentally simple detection of parallel samples on
      miniaturized chips, ideal for personalized medicine of the 21st century. Nucleic
      acid electrochemistry enables, for example, detection of specific DNA sequences
      (for determination of genes or presence of bacteria and viruses, etc.), DNA
      damage analysis and interaction with other molecules, DNA methylation or
      detection of microRNAs as potential cancer bio-markers. In the electrochemistry
      of proteins, great emphasis is put on construction of immunosensors for capturing
      specific proteins (antigens) using antibodies, suitable for diagnostics. From a
      bio-physical point of view, intrinsic electrocatalytic signal of proteins
      sensitive to conformational changes could be useful in discrimination of mutant
      proteins (e. g. p53), native and aggregated forms (alpha-synuclein in Parkinsons
      disease) or for studies of protein interactions with low molecular  weight
      ligands and DNA. Due to an increased interest of scientists in glycoproteins, new
      electrochemical papers emerged aiming at detection of oligosaccharides and
      polysaccharides (i.e. glycans, when part of the protein). These assays employ for
      instance electroactive labels specific for saccharides or lectin bio-sensors
      using lectins which strongly bind glycans. Electrochemical analysis thus appears
      as an interesting tool in current genomics, proteomics and glycomics, as well as
      for cancer diagnostics.

PMID- 24945539
TI  - [Next generation sequencing -  application in clinical practice].
AB  - Development of new sequencing methods allowed faster and more economical genomic
      research. With these technologies, it is now possible to determine the complete
      sequence of human genome in a short time period and at a relatively low cost.
      Introduction of next generation sequencing methods to cancer research provided a
      comprehensive molecular characterization of cancers and enabled deeper insights
      into tumor complexity, heterogeneity and evolution. Next generation technologies
      have been applied to identify new causal mutations in genes in hereditary cancer
      syndromes. More than 15 various tumor types have been already sequenced and
      compared to that of normal cells allowing identification of new cancer driving
      mutations and genome structural rearrangements. In this review, we describe
      technical characteristics of main next generation sequencing platforms, briefly
      overview their pros and cons and clinical perspective.

PMID- 24945540
TI  - [Development of PCR methods and their applications in oncological research and
      practice].
AB  - Since its discovery, PCR has become a conventional method of molecular biology
      research laboratories and an indispensable tool in diagnostic medicine. Multiple
      variants of the PCR technique were developed, which enable the analysis of
      different bio-logical materials at different amounts and reaction conditions.
      This article briefly summarizes the PCR approaches and points out their
      applications in oncological research and practice.

PMID- 24945541
TI  - [Methods for analysis of protein-protein and protein-ligand interactions].
AB  - In order to maintain cellular homeostasis, cellular proteins coexist in complex
      and variable molecular assemblies. Therefore, understanding of major
      physiological processes at molecular level is based on analysis of protein
      protein interaction networks. Firstly, composition of the molecular assembly has
      to be qualitatively analyzed. In the next step, quantitative bio-chemical
      properties of the identified protein-protein interactions are determined.
      Detailed information about the protein-protein interaction interface can be
      obtained by crystallographic methods. Accordingly, the insight into the molecular
      architecture of these protein-protein complexes allows us to rationally design
      new synthetic compounds that specifically influence various physiological or
      pathological processes by targeted modulation of protein interactions. This
      review is focused on description of the most used methods applied in both
      qualitative and quantitative analysis of protein-protein interactions. Co-
      immunoprecipitation and affinity co- precipitation are basic methods designed for
      qualitative analysis of protein binding partners. Further bio-chemical analysis
      of the interaction requires definition of kinetic and thermodynamic parameters.
      Surface plasmon resonance (SPR) is used for description of affinity and kinetic
      profile of the interaction, fluorescence polarization (FP) method for fast
      determination of inhibition potential of inhibitors and isothermal titration
      calorimetry (ITC) for definition of thermodynamic parameters of the interaction
      (G, H and S). Besides the importance of uncovering the molecular basis of protein
      interactions for basic research, the same methodological approaches open new
      possibilities in rational design of novel therapeutic agents.

PMID- 24945542
TI  - [Detection of protein-protein interactions by FRET and BRET methods].
AB  - Nowadays, in vivo protein-protein interaction studies have become preferable
      detecting meth-ods that enable to show or specify (already known) protein
      interactions and discover their inhibitors. They also facilitate detection of
      protein conformational changes and discovery or specification of signaling
      pathways in living cells. One group of in vivo methods enabling these findings is
      based on fluorescent resonance energy transfer (FRET) and its bio-luminescent
      modification (BRET). They are based on visualization of protein-protein
      interactions via light or enzymatic excitation of fluorescent or bio-luminescent
      proteins. These methods allow not only protein localization within the cell or
      its organelles (or small animals) but they also allow us to quantify fluorescent
      signals and to discover weak or strong interaction partners. In this review, we
      explain the principles of FRET and BRET, their applications in the
      characterization of protein-protein interactions and we describe several findings
      using these two methods that clarify molecular and cellular mechanisms and
      signals related to cancer biology.

PMID- 24945543
TI  - [In situ proximity ligation assay for detection of proteins, their interactions
      and modifications].
AB  - To understand cellular processes and events responsible for their perturbations,
      proteomic analyses are needed in bio-medical research and clinical diagnostics.
      Several techniques based on specifically binding reagents (antibodies) or
      recombinant proteins (GFP fusion protein, methods of fluorescence/ bio
      luminescence resonance energy transfer) are generally used to study protein
      location and activity resulting from secondary modifications and interactions.
      The in situ proximity ligation assay represents a novel technique of in situ
      protein imaging using DNA as a reporter molecule and DNA amplification processes.
      This method enables direct visualization of single molecules, their levels,
      modifications and pattern of interactions in individual fixed cells and tissues.
      Proximity probes consist of specific antibody with attached oligonucleotides that
      are used as reporter molecules for identification of such events. Proximity
      probes guide the formation of a circular DNA strand when bound in close
      proximity. The DNA circle after that serves as a template for rolling  circle
      amplification allowing the interaction to be visualized. Compared to available
      proteomic techniques benefiting from genetic engineering, in situ PLA enables
      study of endogenous proteins in their natural environment and thus can be used
      for clinical specimens. The areas of applicability where proximity ligation
      procedure can be used include any research field where protein interaction
      measurements are important, such as signal-ing pathway studies, monitoring of
      pharmacological treatment targets and oncological diagnostics.

PMID- 24945544
TI  - [Protein expression and purification].
AB  - Production of recombinant proteins is essential for many applications in both
      basic research and also in medicine, where recombinant proteins are used as
      pharmaceuticals. This review summarizes procedures involved in recombinant
      protein expression and purification, including molecular cloning of target genes
      into expression vectors, selection of the appropriate expression system, and
      protein purification techniques. Recombinant DNA technology allows protein
      engineering to modify protein stability, activity and function or to facilitate
      protein purification by affinity tag fusions. A wide range of cloning systems
      enabling fast and effective design of expression vectors is currently available.
      A first choice of protein expression system is usually the bacteria Escherichia
      coli. The main advantages of this prokaryotic expression system are low cost and
      simplicity; on the other hand this system is often unsuitable for production of
      complex mammalian proteins. Protein expression mediated by eukaryotic cells
      (yeast, insect and mammalian cells) usually produces properly folded and
      posttranslationally modified proteins. How-ever, cultivation of insect and,
      especially, mammalian cells is time consuming and expensive. Affinity tagged
      recombinant proteins are purified efficiently using affinity chromatography. An
      affinity tag is a protein or peptide that mediates specific binding to a
      chromatography column, unbound proteins are removed during a washing step and
      pure protein is subsequently eluted.

PMID- 24945545
TI  - [Quantitative mass spectrometry and its utilization in oncology].
AB  - Cancers are genetically and clinically very heterogeneous diseases; therefore,
      various proteomic studies have been trying to find bio-markers which can
      facilitate prognosis, diagnosis or treatment of these oncological diseases. The
      mass spectrometry is an effective tool for identification, quantitation, and
      characterization of biomolecules in the complex bio-logical samples. The first
      step suitable for selection of bio-markers called discovery proteomics provides a
      detailed analysis of the samples contributing to the identification of proteins,
      comparison of their presence in the samples, and selection of the convenient
      candidates for the prospective bio-markers. The next step of proteomics analysis
      is directed towards verification of chosen bio-markers with the approach called
      targeted proteomics. This technique evaluates presence and quantity of the
      proteins (biomarkers) in clinically precisely defined samples. This article
      focuses on the description of various approaches suitable for the quantitative
      analysis of the proteins connected with mass spectrometry.

PMID- 24945546
TI  - [Analysis of protein using mass spectrometry].
AB  - Recently, mass spectrometry has become a powerful tool in cancer research. Mass
      spectrometry represents the method that allows identification, quantification and
      characterization of proteins in bio-logical samples. Nowadays, it is mainly used
      for bio-marker discovery that can enable early detection of cancer. This article
      is focused on protein analysis by mass spectrometry. At first, mass spectrometry
      and its importance in proteomics are described. Subsequently ionization type and
      mass analyzers are discussed. This relates to the possibility of online or
      offline analysis connection with separation techniques, such as liquid
      chromatography and electrophoresis. Different approaches for preparing proteins
      and methods of analysis of bio-molecules using mass spectrometers are described.
      In addition, the possibility of mass spectrometric analyses of samples and data
      processing are discussed.

PMID- 24945547
TI  - [p SRM, SWATH and HRM -  targeted proteomics approaches on TripleTOF 5600+ mass
      spectrometer and their applications in oncology research].
AB  - Development of novel diagnostic and therapeutic approaches in cancer research
      requires sensitive and quantitative assays for determination of cancer associated
      proteins in clinical samples. Novel quantitative targeted proteomic approaches
      are overviewed in this communication. A major advantage of selected reaction
      monitoring (SRM) and pseudo- SRM lies in the selective and sensitive
      quantification of selected proteins in large sample sets. As such, they represent
      an alternative to immunochemical approaches. On the other hand, the potential of
      HRM and SWATH lies in recording of digital fingerprints, which enable post
      acquisition quantitative proteomic data mining on a similar basis to SRM. This
      article shows applications of targeted proteomics in a number of cancer research
      studies where they were used for quantification and validation of current or
      potential protein bio-markers and to study their role in cancer development and
      progression.

PMID- 24945548
TI  - [Ananlysis of phosphoproteins and signalling pathways by quantitative
      proteomics].
AB  - Protein phosphorylation is a key regulator in cellular signaling pathways. It is
      involved in most cellular events in which interplay between phosphatases and
      kinases strictly controls bio-logical processes, such as differentiation,
      proliferation and apoptosis. Altered or defective signaling pathways often result
      in various diseases, emphasizing the importance of studying the phosphoproteome.
      The abundance of phosphoproteins in the proteome is often very low, which
      requires specific and highly sensitive approaches. By using quantitative
      proteomics methods, we are able to analyze changes in abundance of proteins and
      their posttranslational modifications and then changes in signaling pathways. In
      this review, we describe quantitative proteomics methods, which could be used for
      study of phosphoproteins and their connection in signaling pathways.

PMID- 24945549
TI  - [New trends in the study of protein glycosylation in oncological diseases].
AB  - Glycomics and glycoproteomics represent relatively new directions in detail
      analyses of complex bio-logical media. These areas of increasing importance to
      cancer research complement the more established genomic profiling and proteomics.
      Glycoproteins are being increasingly recognized as important in cellular
      interactions and adhesion. Structural alterations of their glycan moieties seem
      to occur in different cancer conditions. We review current directions in glycomic
      profiling and glycoproteomic investigations of bio-logical fluids and tissues
      pertaining to cancer. The used methods rely on capillary separation techniques,
      mass spectrometry, and the glycan and lectin arrays. They all show considerable
      promise for new diagnostic and prognostic measurements.

PMID- 24945551
TI  - ["Technetium crisis" -  causes, possible solutions and consequences for planar
      scintigraphy and SPECT diagnostics].
AB  - Nuclear medicine is an important field of nuclear medicine, especially thanks to
      its role in in vivo imaging of important processes in human organism. An
      overwhelming majority of nuclear medicine examinations comprises of planar
      scintigraphy and single photon emission computed tomography, for decades relying
      on the labeling by metastable technetium nuclide (99mTc), used with a great
      diversity of ligands for various applications. Nuclear medicine departments
      utilize commercially available molybdenum technetium generators, being able to
      elute the nuclide at any time and prepare the radiopharmaceutical. The mother
      nuclide, molybdenum-99 (99Mo), is produced in just a handful of places around the
      world. The production places are without exception research nuclear reactors
      working far past their life expectancy. A concurrent temporary shutdown of two of
      them in the year 2009 caused a critical worldwide shortage of 99mTc. An
      unavoidable permanent shutdown of part of these capacities in the second decade
      of the 21st century will cause the second, and this time rather permanent
      "technetium crisis". The article focuses on history, present, potential future
      and possible solutions in regard to SPECT diagnostics.

PMID- 24945550
TI  - [Current trends in using PET radiopharmaceuticals for diagnostics in oncology].
AB  - Nuclear medicine is an important field of modern medicine, particularly thanks to
      its role in in vivo imaging of important processes in human organism. This is
      possible thanks to the use of radiopharmaceuticals, specific substances labeled
      by radioactive nuclide, its distribution in the body can be visualized by
      specialized scanners and, based on the knowledge of physiological patterns, dia
      gnosis can be determined. Positron emission tomography (PET) is a modern and in
      many ways indispensable method of nuclear medicine. The spectrum of
      radiopharmaceuticals available in recent years is broadening thanks to a
      coordinated effort of manufacturers of synthesis equipment, chemists and
      potential users -  physicians. This review focuses on the development in the PET
      radiopharmaceutical field in the last five years, with an emphasis on oncological
      applications of PET.

PMID- 24945552
TI  - [Vitamin D as an important steroid hormone in breast cancer].
AB  - Vitamin D is the third steroid hormone playing important bio-logical roles in the
      development of breast cancer. Decreased plasma levels of its 25-
      hydroxyderivative, 25OHD, display robust associations with higher incidence of
      breast cancer and shorter overall survival. Although no consensus exists, most
      authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas
      levels higher than 375 nmol/ l can be potentially toxic with higher risk of
      hypercalcemia. To date, no data are available on the optimal levels of vitamin D
      related to the risk of breast cancer development, its phenotype features and the
      course of the disease. Published studies mostly describe associations among
      higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The
      polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be
      associated with higher disease incidence and also be of negative prognostic
      significance in breast cancer. This review presents an overall summary of the
      current knowledge and publications on vitamin D and breast cancer.

PMID- 24945553
TI  - Long-term maintenance of smartphone and PDA use in individuals with moderate to
      severe memory impairment.
AB  - In an earlier paper we described a structured, theory-driven training programme
      which was administered to 10 individuals with moderate-to-severe memory
      impairment. All individuals received an errorless-fading-of-cues protocol in the
      use of personal digital assistants (PDAs) or smartphones (Svoboda, Richards,
      Leach, & Mertens, 2012) and demonstrated generalisation of acquired skills to day
      to-day memory challenges. Maintenance of intervention gains over the long-term is
      another indicator of successful generalisation. Here we present the maintenance
      of device use in the same group of individuals 12 to 19 months after programme
      completion. A within-subject, ABABB multi-case experimental design was used to
      evaluate the impact of PDA or smartphone use on day-to-day memory functioning at
      baseline, immediately post-intervention, at return to baseline, and at short-term
      and long-term follow-up. Results presented here focus predominantly on long-term
      follow-up. All 10 individuals showed maintenance of gains in day-to-day
      functioning as quantified across several ecologically valid questionnaire and
      task-based measures. This was corroborated by family members with whom six of the
      participants resided. This study further demonstrates the programme's clinical
      effectiveness in enabling individuals with moderate-to-severe memory impairment
      to function more independently and with greater confidence up to 19 months
      following programme completion.

PMID- 24945554
TI  - Health in the post-2015 agenda: three considerations in moving forward.

PMID- 24945555
TI  - Framework for assessing stewardship of the oral health system in Islamic Republic
      of Iran.
AB  - This study designed a framework for assessing the stewardship function of the
      oral health system in Islamic Republic of Iran. The modified RAND
      Corporation/University of California Los Angeles (RAND-UCLA) Appropriateness
      Method was used in a 2-step process that combined literature evidence and the
      collective judgement of experts. After a comprehensive literature review, policy
      instruments related to stewardship components were extracted as candidate
      standards and categorized according to the 6 sub-functions of stewardship
      (accountability; defining strategic direction; alignment of policy objectives and
      organizational structure; regulation; intersectoral leadership; and generation of
      intelligence). Five key informants then rated the appropriateness of the 85
      standards on a 5-point Likert scale. The 38 highest ranked standards, including
      at least 2 standards in each of the 6 sub-functions, formed a set of proposed
      standards for evaluating the current stewardship of oral health system. Piloting
      of the instrument will be reported separately. 

PMID- 24945556
TI  - Patients' attitudes towards the role of dentists in tobacco cessation counselling
      after a brief and simple intervention.
AB  - Dental professionals are in a unique position to promote smoking cessation among
      their patients. We evaluated the effects of a brief counselling intervention by a
      dentist on patients' attitude towards the role of dentists in tobacco cessation
      programmes. In a semi-experimental study in Tehran, Islamic Republic of Iran, 70
      eligible smokers were selected and randomly assigned to intervention and control
      groups. The initial attitudes of the patients regarding tobacco cessation
      counselling services provided by the dentist were determined using a validated
      questionnaire. The intervention group received a brief chair-side counselling by
      a dentist based on the 5 A's approach, while no intervention was provided for the
      control group. At 8-weeks follow-up, smokers receiving the intervention showed
      significantly more positive attitudes towards the role of the dentist in advising
      patients to quit smoking compared with those in the control group. More
      responsibility could be transferred to dentists for tobacco prevention. 

PMID- 24945558
TI  - Perceptions, attitudes, and practices towards research among resident physicians
      in training in Saudi Arabia.
AB  - Health research training forms an important part of medical education. This cross
      sectional study examined the attitudes to research, perceived barriers to
      research and experience of participation in research projects among resident
      physicians in Saudi Arabia. A self-administered email questionnaire was completed
      by 191/207 residents working in different specialties and regions of Riyadh. A
      majority (97.9%) agreed that research is essential and improves health care and
      86.9% that it helps in building a future academic career. Lack of research
      training (93.2%), lack of time (89.5%), work-related stress (83.2%) and lack of
      supervisors (73.3%) were perceived barriers to doing research. Only 58 (30.4%)
      had had any research involvement. Involvement in research was significantly more
      likely for residents at an advanced level of training than at earlier levels (OR
      3.50, 95% CI: 1.1-11.1) and less likely for those who had 1 or 2 children during
      residency than those who had none (OR 0.29, 95% CI: 0.1-0.8). 

PMID- 24945557
TI  - Attitudes of dental patients towards participation in research.
AB  - The attitudes of dental patients towards participation in research and the
      independent socioeconomic factors associated with these attitudes are not known.
      A self-administered questionnaire was distributed to 120 patients attending
      dental clinics in Amman, Jordan. For patients who had previously participated in
      research (n = 28), motivating factors for most (> 75%) included a desire to help
      others and to advance science. Most respondents (81.7%) showed interest in
      participating in questionnaire-based research, but fewer would participate in
      invasive research, e.g. biopsies (22.0%) and drilling teeth (21.2%). Reasons
      given for not participating in research included fear of infectious diseases
      (71.3%) and pain (62.1%). Factors considered important in enhancing research
      participation included being asked to give informed consent (98.2%), fairness in
      selection of participants (97.3%) and the prospect of humanitarian benefit
      (96.5%). Sex and education level were significantly associated with patients'
      perceptions for several of items. To enhance recruitment, researchers should be
      aware of people's perspectives regarding participation in research. 

PMID- 24945559
TI  - Quality of documentation of electronic medical information systems at primary
      health care units in Alexandria, Egypt.
AB  - Limited data are available about the implementation of electronic records systems
      in primary care in developing countries. The present study aimed to assess the
      quality of documentation in the electronic medical records at primary health care
      units in Alexandria, Egypt and to elicit physician's feedback on barriers and
      facilitators to the system. Data were collected at 7 units selected randomly from
      each administrative region and in each unit 50 paper-based records and their
      corresponding e-records were randomly selected for patients who visited the unit
      in the first 3 months of 2011. Administrative data were almost complete in both
      paper and e-records, but the completeness of clinical data varied between 60.0%
      and 100.0% across different units and types of record. The accuracy rate of the
      main diagnosis in e-records compared with paper-based records ranged between
      44.0% and 82.0%. High workload and system complexity were the most frequently
      mentioned barriers to implementation of the e-records system. 

PMID- 24945560
TI  - Capacity building of public health laboratories in Afghanistan: challenges and
      successes (2007-2011).
AB  - The continuing state of conflict and the resulting devastation of infrastructure
      have made Afghanistan exceptionally vulnerable to disease epidemics. The paper
      reports initiatives by the United States Naval Medical Research Unit No. 3 to
      promote capacity building in a number of key medical laboratories and enable the
      Afghans to detect emerging and re-emerging diseases of public health importance.
      Equipment, supplies and laboratory staff training were critical for disease
      diagnosis and fulfillment of obligations of the International Health Regulations
      2005. Accordingly, many diseases outbreaks were recently identified, including
      avian and pandemic influenza, febrile illness, watery diarrhoea, jaundice and
      leishmaniasis. Clinical samples and disease vectors were collected for analysis,
      and microbial isolates were obtained for further characterization. The expanded
      range and enhanced accuracy of laboratory procedures have facilitated selected
      local laboratories to monitor, detect, identify, assess, contain and respond to
      public health threats. Nevertheless, policies of sustainability and infectious
      diseases control need continuous support and emphasis.

PMID- 24945561
TI  - Tuberculosis awareness in Gezira, Sudan: knowledge, attitude and practice case
      control survey.
AB  - This case-control study aimed to assess tuberculosis (TB) awareness and its
      associated sociodemographic characteristics in Gezira, Sudan. New smear-positive
      TB patients registered in Gezira in 2010 (n = 425) and age-matched controls who
      attended the same health facilities for other reasons (n = 850) formed the study
      sample. Awareness was measured using a modified standard World Health
      Organization TB knowledge, attitude and practice instrument. There was no
      significant difference between TB cases and the controls in overall levels of TB
      awareness. About two-thirds of TB cases and controls had good TB awareness.
      Respondents' sex was associated with awareness among the controls. Age, level of
      education, type of residence and type of occupation were significantly associated
      with TB awareness, whereas marital status had no effect. The good level of TB
      awareness found among TB cases and controls is a baseline for further TB
      awareness-raising among the Gezira population. 

PMID- 24945562
TI  - Genotype characterization of occult hepatitis B virus strains among Egyptian
      chronic hepatitis C patients.
AB  - Chronic hepatitis C virus (HCV) infection combined with occult hepatitis B virus
      (HBV) infection has been associated with increased risk of hepatitis, cirrhosis
      and hepatocellular carcinoma. This study aimed to determine the prevalence of
      occult HBV infection among Egyptian chronic HCV patients, the genotype and
      occurrence of surface gene mutations of HBV and the impact of co-infection on
      early response to treatment. The study enrolled 162 chronic HCV patients from
      Ismailia Fever Hospital, Egypt, who were HBV surface antigen-negative. All
      patients were given clinical assessment and biochemical, histological and
      virological examinations. HBV-DNA was detectable in sera from 3 patients out of
      the 40 patients who were positive for hepatitis B core antibody. These 3 patients
      were responsive to combination therapy at treatment week 12; only 1 of them had
      discontinued therapy by week 24. HBV genotype D was the only detectable genotype
      in those patients, with absence of "a" determinant mutations among those
      isolates. 

PMID- 24945563
TI  - [Relationship between blood glucose levels and salivary pH and buffering capacity
      in type II diabetes patients].
AB  - This study was evaluated the relationship between blood glucose levels and
      salivary pH and buffering capacity in type II diabetic patients. The sample
      comprised 210 participants (age ranged 40-60 years). Based on fasting blood
      glucose levels the participants were divided into 3 groups: controls with normal
      blood glucose levels; diabetic patients with levels <= 200 mg/dL; and diabetic
      patients with levels > 200 mg/dL. Salivary pH and buffering capacity were
      determined in a sample of resting (non-stimulated) saliva taken from each
      participant. Salivary pH levels in diabetic patients with blood glucose levels >
      200 mg/dL were lower than in the controls and diabetic patients with levels <=
      200 mg/dL. Salivary pH levels were comparable in controls and diabetic patients
      with blood glucose levels <= 200 mg/dL. Salivary buffering capacity in the 3
      groups was comparable. 

PMID- 24945564
TI  - Curcumin affects beta-catenin pathway in hepatic stellate cell in vitro and in
      vivo.
AB  - OBJECTIVES: Emerging evidence indicates that Wnt/beta-catenin pathway is linked
      to the fibrosis of different organs including liver fibrosis. beta-Catenin
      promotes hepatic stellate cells (HSCs) activation, a key event in the development
      of liver fibrosis, and has emerged as a novel mediator of fibrosis. Curcumin, a
      natural active ingredient derived from turmeric, possesses an inhibitory effect
      on liver fibrosis. This study is aimed to examine whether curcumin affects beta
      catenin expression/activity in HSCs and explores the underlying mechanisms.
      METHODS: The researchers used Western blot, real-time PCR, transfection assay and
      electrophoretic mobility shift assay and employed cultured HSCs and rat model of
      liver injury. KEY FINDINGS: Results showed that curcumin could reduce beta
      catenin protein level in HSCs in vitro and in vivo. Both beta-catenin
      transactivation activity and DNA-binding activity were suppressed by curcumin.
      Moreover, nuclear beta-catenin protein level was decreased by curcumin treatment.
      Further experiments suggested that delta-like homologue 1 contributed to curcumin
      inhibition of beta-catenin transactivation activity in cultured HSCs.
      CONCLUSIONS: Curcumin affects beta-catenin pathway in HSCs and might suggest a
      possible new explanation for the effects of curcumin on HSC activation and liver
      fibrosis.

PMID- 24945565
TI  - Restless Legs Syndrome: Psychiatric Comorbidities Are More Important Than
      Neuroticism.
AB  - Restless legs syndrome (RLS) is often associated with psychopathological
      symptoms. We compared psychiatric diagnoses, psychological complaints, sleep and
      personality traits in RLS patients and a control group The RLS patients also
      answered the IRLS, RLS-6, and QoL-RLS. The RLS patients showed more depressive
      disorders, psychopathological symptoms, and lower well-being than controls, but
      no differences in personality traits. The slightly, but not significantly, higher
      neuroticism found in RLS patients can be explained by the higher rates of
      depression among the patients. It is advisable to screen RLS patients for
      psychiatric comorbidities. The design using a matched control group without sleep
      disorders limits the conclusions that can be drawn regarding the frequency of
      psychiatric diagnoses and controls with sleep problems. 

PMID- 24945566
TI  - Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising
      anticancer leads.
AB  - Zampanolide is a marine natural macrolide and a recent addition to the family of
      microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on
      tubulin assembly and is more potent than paclitaxel against several multi-drug
      resistant cancer cell lines. A high-resolution crystal structure of alphabeta
      tubulin in complex with zampanolide explains how taxane-site microtubule
      stabilizing agents promote microtubule assemble and stability. This review
      provides an overview of current developments of zampanolide and its related but
      less potent analogue dactylolide, covering their natural sources and isolation,
      structure and conformation, cytotoxic potential, structure-activity studies,
      mechanism of action, and syntheses.

PMID- 24945568
TI  - First isolation of Neospora caninum from blood of a naturally infected adult
      dairy cow in Beijing, China.
AB  - Neospora caninum is an important cause of abortion in cattle worldwide, but the
      isolation of a viable parasite from an abortus is difficult, and viable N.
      caninum has not been isolated from any host in China. In the present study,
      peripheral blood samples were collected from a jugular vein of an adult dairy cow
      that had aborted; the cow was seropositive to N. caninum antibodies by ELISA.
      White blood cells were separated and seeded onto Vero cell monolayer cultures for
      parasite isolation. Tachyzoites were first observed in cell culture on day 84
      after initial inoculation. The parasite was confirmed to be N. caninum by gene
      sequencing and immunofluorescence, and by bioassays in BALB/c mice. The new N.
      caninum isolate (NC-Bj) has a unique pattern on microsatellite Cont-14. To our
      knowledge, this is the first successful isolation of N. caninum in China from any
      host.

PMID- 24945569
TI  - Kinematic mapping reveals different spatial distributions of center of pressure
      high-speed regions under somatosensory loss.
AB  - The spatial distribution of center-of-pressure speed during postural tasks and
      its changes due to somatosensory constraint (temporary ischemic hypoxia on
      ankle/feet) were investigated in young, healthy subjects (n = 13). A single high
      speed region in the central region of the statokinesigram was observed during
      postural tasks with full sensory information. A significant increase in the
      quantity of high-speed regions was observed during ischemia and somatosensory
      constraint, whereas a significant increase in the quantity of high-speed regions
      localized more distant to the center of center-of-pressure area occurred under
      somatosensory constraints, suggesting a redirection of center-of-pressure
      trajectory to adjust the position of the center of mass with respect to the
      egocentric reference of balance.

PMID- 24945567
TI  - ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway
      in Caenorhabditis elegans under celecoxib intervention.
AB  - DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal
      pathway (IIS), and this is notably true when Caenorhabditis elegans (C. elegans)
      is used to study the action of anti-aging compounds on IIS activity. However,
      some of these genes may not be specific to DAF-16, even if their expression
      levels are altered when DAF-16 is activated. Celecoxib was reported to extend the
      lifespan of C. elegans through activation of DAF-16. Our results confirmed the
      function of celecoxib on aging; however, we found that the expression of ins-7, a
      DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an
      important role in regulating aging, and its expression is suppressed in C.
      elegans when DAF-16 is activated. However, we found that celecoxib upregulated
      the expression of ins-7 in contrast to its role in DAF-16 activation. Our
      subsequent analysis indicated that the expression level of ins-7 in C. elegans
      was negatively regulated by DAF-16 activity. Additionally, its expression was
      also positively regulated by DAF-16-independent mechanisms, at least following
      external pharmacological intervention. Our study suggests that ins-7 is not a
      specific target gene of DAF-16, and should not be chosen as a reporter for IIS
      activity. This conclusion is important in the study of INSs on aging in C.
      elegans, especially under the circumstance of drug intervention. 

PMID- 24945570
TI  - Molecular aspects, genomic arrangement and immune responsive mRNA expression
      profiles of two CXC chemokine receptor homologs (CXCR1 and CXCR2) from rock
      bream, Oplegnathus fasciatus.
AB  - The CXCR1 and CXCR2 are the prototypical receptors and are the only known
      receptors for mammalian ELR+ (Glu-Leu-Arg) CXC chemokines, including CXCL8
      (interleukin 8). These receptors transduce the ELR+ chemokine signals and operate
      the downstream signaling pathways in inflammation and innate immunity. In this
      study, we report the identification and characterization of CXCR1 and CXCR2 genes
      from rock bream fish (OfCXCR1 and OfCXCR2) at the molecular level. The cDNA and
      genomic DNA sequences of the OfCXCR1 and OfCXCR2 were identified from a
      transcriptome library and a custom-constructed BAC library, respectively. Both
      OfCXCR genes consisted of two exons, separated by an intron. The 5'-flanking
      regions of OfCXCR genes possessed multiple putative transcription factor binding
      sites related to immune response. The coding sequences of OfCXCR1 and OfCXCR2
      encoded putative peptides of 355 and 360 amino acids (aa), respectively. The
      deduced aa sequences of OfCXCR1 and OfCXCR2 comprised of a G-protein coupled
      receptors (GPCR) family 1 profile with a GPCR signature and a DRY motif. In
      addition, seven conserved transmembrane regions were predicted in both OfCXCRs.
      While our multiple alignment study revealed the functionally significant
      conserved elements of the OfCXCR1 and OfCXCR2, phylogeny analyses further
      confirmed their position in teleost sub clade, in which they manifested an
      evolutionary relatedness with other fish counterparts. Based on comparative
      analyses, teleost CXC chemokine receptors appear to be distinct from their non
      fish orthologs in terms of evolution (both CXCR1 and CXCR2) and genomic
      organization (CXCR2). Quantitative real-time PCR (qPCR) detected the transcripts
      of OfCXCR1 and OfCXCR2 in eleven examined tissues, with higher levels in head
      kidney, kidney and spleen highlighting their crucial importance in immunity. In
      vitro stimulation of peripheral blood leukocytes (PBLs) with concanavalin A (Con
      A) resulted in modulation of OfCXCR2 transcription, but not that of OfCXCR1. In
      addition, the magnitude of the OfCXCR1 and OfCXCR2 transcripts in head kidney and
      spleen was differentially increased after the in vivo administration of immune
      stimulants, LPS and poly I:C and in the infection models injected with rock bream
      irido virus, Edwardsiella tarda and Streptococcus iniae. These lines of evidence
      suggest that these receptors may play an important role(s) in immune responsive
      signaling during pathogenesis of rock bream.

PMID- 24945571
TI  - Anti-viral gene induction is absent upon secondary challenge with double-stranded
      RNA in the Pacific oyster, Crassostrea gigas.
AB  - Oyster farming is one of the most important aquaculture industries in the world.
      However, its productivity is increasingly limited by viral disease and we do not
      yet have management practices, such as protective vaccination, that can control
      these disease outbreaks. Hence, in the current study we investigated the
      expression of known anti-viral genes in oysters (Crassostrea gigas) in response
      to primary and secondary encounter with a virus associated molecular pattern
      (dsRNA), and tested whether a common form of epigenetic gene regulation (DNA
      methylation) was associated with the expression of these anti-viral genes.
      Injection of dsRNA into the adductor muscle resulted in the rapid and transient
      expression of virus recognition receptors (TLR & MDA5), whereas several anti
      viral signalling (IRF & SOC-1) and effector (PKR & viperin) genes were still up
      regulated at one week post primary challenge (p < 0.05). This primary encounter
      with dsRNA appeared to deplete the immune system because anti-viral gene
      induction was absent in the gills when oysters were given a second injection of
      dsRNA at 1-week post-primary injection. The expression of DNA methylation genes
      (DNMT1, DNMT3b, TDG, TET2) and DNA methylation profiles up-stream of specific
      anti-viral genes (STING, SOC-1 & Viperin) did not change in response to dsRNA
      injection (p > 0.05). These results collectively suggest that C. gigas does not
      have an enhanced anti-viral gene response (immune-priming) to secondary dsRNA
      challenge and that the sustained up-regulation of anti-viral signalling and
      effector genes following primary challenge is unlikely to be associated with
      upstream DNA methylation levels.

PMID- 24945572
TI  - Innate immune response of Indian major carp, Labeo rohita infected with oomycete
      pathogen Aphanomyces invadans.
AB  - The fish pathogenic oomycete Aphanomyces invadans is the causative agent of
      epizootic ulcerative syndrome (EUS), a fish disease of international significance
      and reportable to the World Organisation for Animal Health. In spite of the
      current and potential impact of A. invadans infection on fisheries and
      aquaculture sectors of the world, very little is known about the host-A. invadans
      interactions. In the present study, following experimental infection with A.
      invadans in one of the Indian major carps, Labeo rohita, sequential changes in
      various innate immune parameters were monitored. The results indicated that at
      early stages of infection, no significant changes in any of the studied innate
      immune parameters were observed. However, at the advanced stages of infection
      from 6 to 12 days post infection (dpi), the respiratory burst and alternate
      complement activity were significantly higher whereas lysozyme, antiproteases and
      alpha-2 macroglobulin values were significantly lower than the control group and
      also from the infected group at earlier stages of infection. Since, the
      possibility of vaccination of fish against A. invadans appears remote due to
      difficulties in eliciting a specific antibody response, the information generated
      in the present study could be useful for developing strategies for improving
      resistance to A. invadans infection by stimulating the innate immunity through
      immunomodulation.

PMID- 24945573
TI  - Identification and comparative analysis of the Pseudosciaena crocea microRNA
      transcriptome response to poly(I:C) infection using a deep sequencing approach.
AB  - Two sRNA libraries with or without poly(I:C) infection of large yellow croaker
      Pseudosciaena crocea were constructed and sequenced using the high-throughput
      Illumina/Solexa deep sequencing technology. The high-throughput sequencing
      pipeline yielded 163,79,272 and 217,07,070 raw reads corresponding to 132,27,594
      and 206,86,409 clean reads for the normal and infected libraries, respectively.
      Bioinfromatic analysis identified 534 miRNAs, of which, 158 miRNAs were known in
      miRBase 20.0 and the remaining 376 were not found homology to any known metazoan
      miRNAs, suggesting a possible species-specificity. We analyzed the significance
      of differently expressed miRNAs between two libraries using pairwise comparison.
      There was significant differential expression of 112 miRNAs (p < 0.001) between
      two libraries. Thereinto, a number of known miRNAs were identified immune
      related. Real-time quantitative PCR experiments (RT-qPCR) were preformed for 6
      miRNAs of the two samples, and agreement was found between the sequencing and RT
      qPCR data. To our knowledge, this is the first comprehensive study of miRNAs in
      P. crocea and of expression analysis of P. crocea miRNAs in response to poly(I:C)
      infection, and many miRNAs were differentially regulated under normal and
      infection conditions. These findings deepened our understanding of the role of
      miRNAs in the intricate host's immune system, and should be useful to develop new
      control strategies for host immune defense against various foreign infection in
      P. crocea.

PMID- 24945574
TI  - RNA interference technology used for the study of aquatic virus infections.
AB  - Aquaculture is one of the most important economic activities in Asia and is
      presently the fastest growing sector of food production in the world. Explosive
      increases in global fish farming have been accompanied by an increase in viral
      diseases. Viral infections are responsible for huge economic losses in fish
      farming, and control of these viral diseases in aquaculture remains a serious
      challenge. Recent advances in biotechnology have had a significant impact on
      disease reduction in aquaculture. RNAi is one of the most important technological
      breakthroughs in modern biology, allowing us to directly observe the effects of
      the loss of specific genes in living systems. RNA interference technology has
      emerged as a powerful tool for manipulating gene expression in the laboratory.
      This technology represents a new therapeutic approach for treating aquatic
      diseases, including viral infections. RNAi technology is based on a naturally
      occurring post-transcriptional gene silencing process mediated by the formation
      of dsRNA. RNAi has been proven widely effective for gene knockdown in mammalian
      cultured cells, but its utility in fish remains unexplored. This review aims to
      highlight the RNAi technology that has made significant contributions toward the
      improvement of aquatic animal health and will also summarize the current status
      and future strategies concerning the therapeutic applications of RNAi to combat
      viral disease in aquacultured organisms. 

PMID- 24945575
TI  - Aroclor 1254 inhibits the chemiluminescence response of peritoneal cavity cells
      from sharpsnout sea bream (Diplodus puntazzo).
AB  - Chronic exposure to polychlorinated biphenyls (PCBs) affect the immune system of
      fish and could lead to a decreased disease resistance. The effects of Aroclor
      1254, PCB mixtures, on the Diplodus puntazzo innate immunity were examined by
      assaying the zymosan stimulated chemiluminescence response (CL) of peritoneal
      cavity cells (PCCs) at various times (1, 24, 48 h and 1-4 weeks) from
      intraperitoneal injection of the xenobiotic (1 mg kg(-1) body weight). Controls
      were performed by assaying cells from medium-treated fish. Since the kinetic of
      the chemiluminescence response showed the highest peak at 25 min after the
      zymosan stimulation of the cells, the values found at that time were considered.
      The CL enhancement observed at 1 h after the treatment with xenobiotic was
      followed by a decreased response at 24 h and appeared to be lower at 1-4 weeks
      when compared to the CL response of the control, suggesting a protracted effect
      of PCBs on the peritoneal cavity. Since PCCs incubated in vitro for 1 h with 0.05
      and 0.1 MUg ml(-1) Aroclor showed an enhanced CL, the effect of the xenobiotic
      could be exerted on the cell responsiveness to zymosan. It is known that fish CL
      response of PCCs can be imputed to phagocyte (macrophages and neutrophils)
      activation, these cells and their responsiveness to zymosan can be used in
      immunotoxicology assay to monitor the fish health in polluted environment.

PMID- 24945576
TI  - Impact of 5-azacytidine on rat decidual cell proliferation.
AB  - The DNA demethylating agent 5-azacytidine (5-azaC) has a teratogenic influence
      during rat development influencing both the embryo and the placenta. Our aim was
      to investigate its impact on early decidual cell proliferation before the
      formation of placenta. Thus, female Fischer rats received 5-azaC (5 mg/kg, i.p.)
      on the 2nd, 5th or 8th day of gestation and the decidual tissues were harvested
      on gestation day 9. They were then analysed immunohistochemically for expression
      of cell proliferation marker proliferating cell nuclear antigen (PCNA) in
      decidual cells and for global DNA methylation using the coupled restriction
      enzyme digestion, random amplification and pyrosequencing assays. We found that 5
      azaC administered on the 5th and 8th (but not on 2nd) day of gestation led to
      increased PCNA expression in decidual cells compared with untreated controls. No
      significant changes in DNA methylation were detected, with either method, in any
      of the treated rat groups compared with untreated controls. Thus, we conclude
      that 5-azaC can stimulate decidual cell proliferation without simultaneously
      changing global DNA methylation level in treated cells.

PMID- 24945577
TI  - Quinapril treatment abolishes diabetes-associated atherosclerosis in
      RAGE/apolipoprotein E double knockout mice.
AB  - OBJECTIVE/RATIONALE: Both the renin-angiotensin system (RAS) and the receptor for
      advanced glycation end products (RAGE) potentiate diabetes-associated
      atherosclerosis (DAA). We assessed the effectiveness of concomitant RAS and RAGE
      inhibition on DAA. METHODS: Diabetic (5 * 55 mg/kg streptozotocin daily) and non
      diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were
      treated with quinapril (30 mg/kg/day) for 20 weeks. At the end of the study
      aortic plaques were assessed. RESULTS: Diabetic RAGE/apoE DKO showed
      significantly less plaque area than diabetic apoE KO mice. Plaque deposition was
      almost abolished in quinapril treated diabetic RAGE/apoE DKOs, with significant
      attenuation of vascular collagen deposition, nitrotyrosine staining, and reduced
      macrophage infiltration. Expression of the advanced glycation end product
      receptor 3 (galectin 3) was also significantly reduced. CONCLUSION: Concomitant
      inhibition of RAS and RAGE signalling almost completely inhibited the development
      of experimental DAA. A dual therapeutic approach may be a superior strategy for
      the treatment of diabetic macrovascular disease..

PMID- 24945579
TI  - 3-(Methoxycarbonylmethylene)isobenzofuran-1-imines as a new class of potential
      herbicides.
AB  - A novel class of potential herbicides, the 3-(methoxycarbonylmethylene)
      isobenzofuran-1-imines, has been discovered. The herbicidal activity has been
      tested on two particular molecules, (E)-methyl 2-[3-(butylimino)isobenzofuran
      1(3H)-ylidene]acetate (1) and (E)-methyl 2-phenyl-2-[3-(phenylimino)isobenzofuran
      1(3H)-ylidene]acetate (2), prepared by palladium-catalyzed oxidative
      carbonylation of 2-alkynylbenzamides. Both compounds 1 and 2 showed a strong
      phytotoxic effect on both shoot and root systems of Arabidopsis thaliana. The
      effects observed on the shoot were similar for both molecules, but while compound
      1 showed a stronger effect on root parameters (such as primary root length, root
      hair and density, showing lower ED50 values), compound 2 caused important
      malformations in root morphology. Our results indicate that these molecules are
      very promising synthetic herbicides. 

PMID- 24945578
TI  - Biological activities and phytochemical profiles of extracts from different parts
      of bamboo (Phyllostachys pubescens).
AB  - Besides being a useful building material, bamboo also is a potential source of
      bioactive substances. Although some studies have been performed to examine its
      use in terms of the biological activity, only certain parts of bamboo, especially
      the leaves or shoots, have been studied. Comprehensive and comparative studies
      among different parts of bamboo would contribute to a better understanding and
      application of this knowledge. In this study, the biological activities of
      ethanol and water extracts from the leaves, branches, outer culm, inner culm,
      knots, rhizomes and roots of Phyllostachys pubescens, the major species of bamboo
      in Japan, were comparatively evaluated. The phytochemical profiles of these
      extracts were tentatively determined by liquid chromatography-mass spectrometry
      (LC-MS) analysis. The results showed that extracts from different parts of bamboo
      had different chemical compositions and different antioxidative, antibacterial
      and antiallergic activities, as well as on on melanin biosynthesis. Outer culm
      and inner culm were found to be the most important sources of active compounds. 8
      C-Glucosylapigenin, luteolin derivatives and chlorogenic acid were the most
      probable compounds responsible for the anti-allergy activity of these bamboo
      extracts. Our study suggests the potential use of bamboo as a functional
      ingredient in cosmetics or other health-related products. 

PMID- 24945580
TI  - Magnetic Pycnoporus sanguineus-loaded alginate composite beads for removing dye
      from aqueous solutions.
AB  - Dye pollution in wastewater is a severe environmental problem because treating
      water containing dyes using conventional physical, chemical, and biological
      treatments is difficult. A conventional process is used to adsorb dyes and filter
      wastewater. Magnetic filtration is an emerging technology. In this study,
      magnetic Pycnoporus sanguineus-loaded alginate composite beads were employed to
      remove a dye solution. A white rot fungus, P. sanguineus, immobilized in alginate
      beads were used as a biosorbent to remove the dye solution. An alginate polymer
      could protect P. sanguineus in acidic environments. Superparamagnetic
      nanomaterials, iron oxide nanoparticles, were combined with alginate gels to form
      magnetic alginate composites. The magnetic guidability of alginate composites and
      biocompatibility of iron oxide nanoparticles facilitated the magnetic filtration
      and separation processes. The fungus cells were immobilized in loaded alginate
      composites to study the influence of the initial dye concentration and pH on the
      biosorption capacity. The composite beads could be removed easily post-adsorption
      by using a magnetic filtration process. When the amount of composite beads was
      varied, the results of kinetic studies of malachite green adsorption by
      immobilized cells of P. sanguineus fitted well with the pseudo-second-order
      model. The results indicated that the magnetic composite beads effectively
      adsorbed the dye solution from wastewater and were environmentally friendly. 

PMID- 24945581
TI  - A PPARgamma, NF-kappaB and AMPK-dependent mechanism may be involved in the
      beneficial effects of curcumin in the diabetic db/db mice liver.
AB  - Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the
      ginger family which has been used to treat biliary disorders, anorexia, cough,
      rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and
      diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms
      of action include the modulation of signal transduction cascades and effects on
      gene expression, however they remain to be elucidated. In this study, the
      expression of some proteins responsible for transcription factors, inflammation,
      and metabolic control were evaluated by western blot in 15-week-old db/db mice
      livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition,
      nitrosative stress was evaluated. Curcumin increased the expression of AMPK and
      PPARgamma, and diminished NF-kappaB protein in db/db mice. However, it did not
      modify the expression of PGC-1alpha or SIRT1. Nitrosative stress present in db/db
      mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and
      was not reverted with curcumin. In conclusion, curcumin regulates the expression
      of AMPK, PPARgamma, and NF-kappaB; suggesting a beneficial effect for treatment
      of T2DM complications. In order to observe best beneficial effects it is
      desirable to administer curcumin in the earlier states of T2DM. 

PMID- 24945582
TI  - Elevation of plasma cell-free hemoglobin in pulmonary arterial hypertension.
AB  - BACKGROUND: Cell-free hemoglobin (CFH) is a potent nitric oxide scavenger
      associated with poor outcomes in several diseases. Pulmonary arterial
      hypertension (PAH) is characterized by reduced nitric oxide availability. We
      hypothesized that CFH would be elevated in PAH and would associate with
      hemodynamics and clinical outcomes. METHODS: We measured CFH in 200 consecutively
      evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein
      type 2 (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with
      pulmonary venous hypertension (PVH). CFH values were tested for association with
      hemodynamics, time to hospitalization, and death. RESULTS: CFH was elevated in
      patients with PAH and BMPR2 carriers compared with healthy subjects and patients
      with PVH (P <= .01 all comparisons). There were no differences in CFH across PAH
      subtypes. CFH modestly correlated with mean pulmonary artery pressure (rho =
      0.16, P = .03) and pulmonary vascular resistance (rho = 0.21, P = .01) and
      inversely with cardiac index (rho = -0.18, P = .02) in patients with PAH. CFH was
      not associated with hemodynamic response to nitric oxide or death. Patients with
      the highest CFH levels had increased risk of PAH-related hospitalization when
      adjusted for age, sex, and PAH cause (hazard ratio, 1.69; 95% CI ,1.08-2.66; P =
      .02). CONCLUSIONS: CFH is elevated in patients with PAH and BMPR2 carriers
      compared with healthy subjects and patients with PVH. Elevated CFH levels are
      independently associated with an increased risk of hospitalization. Further study
      is required to understand the mechanism of CFH elevation and the potential
      pathologic contribution of CFH in PAH.

PMID- 24945584
TI  - Ten-year follow up after laparoscopic suture rectopexy for full-thickness rectal
      prolapse.
AB  - AIM: Studies have shown that recurrence rates of full-thickness rectal prolapse
      (FTRP) 5 years after surgery can quadruple at 10 years. This study aimed to
      evaluate the impact of laparoscopic suture rectopexy for FTRP on recurrence rates
      and functional outcome at a median follow up of 10 years. METHOD: Prospectively
      collected data for patients who underwent laparoscopic suture rectopexy for FTRP
      between 1993 and 2006 were analysed. Laparoscopic rectopexy consisted of
      circumferential mobilization of the rectum down to the levator followed by suture
      suspension to promontory. Patients with preexisting constipation or who were
      unfit for general anaesthesia were not included. Incontinence, quality of life
      and constipation were assessed by validated scores. Recurrence-free curves were
      generated using the Kaplan-Meier method. RESULTS: One hundred and seventy-nine
      patients with a median age of 62 (15-93) years including 174 women and five men
      underwent laparoscopic suture rectopexy. There was no mortality. The 30-day
      complication rate was 4% (partial transection of the left ureter, pneumonia,
      urinary tract infection, urinary retention, superficial surgical site infection).
      Data on 172 patients (96%) were available at follow up. There were 10 recurrences
      of FTRP at 5-year follow up giving a crude recurrence rate of 6%. The actuarial
      10-year recurrence rate was 20% (95% CI, 10.8-20.1). Follow-up continence (P <
      0.0001) and quality of life were better than preoperatively: lifestyle (P <
      0.001), coping (P < 0.001), self-perception (P < 0.005), embarrassment (P <
      0.06). Constipation was unchanged. CONCLUSION: Laparoscopic suture rectopexy led
      to few complications, a recurrence rate of 20%, improved continence and quality
      of life with no worsening of constipation at 10 years.

PMID- 24945583
TI  - Rapid access to novel 1,2,3-triazolo-heterocyclic scaffolds via tandem
      Knoevenagel condensation/azide-alkyne 1,3-dipolar cycloaddition reaction in one
      pot.
AB  - An operationally simple, one-pot, two-step cascade method has been developed to
      afford biologically important fused 1,2,3-triazolo-heterocyclic scaffolds from 2
      alkynyl aryl(heteroaryl) aldehydes and phenacyl azides. This unique atom
      economical transformation engages four reactive centers (aldehyde, alkyne, active
      methylene, and azide) under metal-free catalysis. 

PMID- 24945585
TI  - Yanagihara facial nerve grading system as a prognostic tool in Bell's palsy.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of the Yanagihara
      facial nerve grading system in assessing the course of recovery and in
      determining the probability of a complete recovery of Bell's palsy within 1 week
      after onset. STUDY DESIGN: Retrospective study of patients at a single trial
      center. SETTING: Tertiary referral center. PATIENTS: Six hundred sixty-four
      patients with Bell's palsy were assigned to three groups by degree of facial
      palsy using the Yanagihara 40-point system. MAIN OUTCOME MEASURE: The rate of
      recovered patients was assessed until 6 months after onset. RESULTS: Ultimately,
      151 (23.1%) patients were assessed with mild palsy, 286 (43.7%) with moderate
      palsy, and 217 (33.2%) with severe palsy. The average Yanagihara score in the
      recovered patients was 15.7, whereas the score in the nonrecovered patients was
      8.4. The rate of recovered patients in the mild group was 99.3%, that in the
      moderate group was 95.1%, and that in the severe group was 80.2%. These
      differences among the groups were significant (p < 0.05). CONCLUSION: The
      Yanagihara system was able to distinguish the probability of a complete recovery
      of the facial palsy within 1 week after the onset of palsy. We believe that the
      key point in improving the prognosis of Bell's palsy is to diagnose the severity,
      using the Yanagihara system, and to treat it promptly to prevent progressive
      nerve degeneration.

PMID- 24945586
TI  - Dietary modification as adjunct treatment in Meniere's disease.

PMID- 24945587
TI  - Impingement of the carotid canal on the basal turn of the cochlea as pertaining
      to cochlear implantation.
AB  - HYPOTHESIS: To evaluate the relation of the basal turn of the cochlea with the
      carotid canal as pertaining to cochlear implantation. BACKGROUND: Cochlear
      implantation is an established mode of treatment for patients with bilateral
      profound sensorineural hearing loss. An intricate knowledge of both the typical
      and atypical topography of the cochlea with the carotid canal is essential for
      safely conducting cochlear implantation. DESIGN: Fifty-eight cadaveric temporal
      bones were microdissected to expose the medial wall of the middle ear. To open
      the basal turn of the cochlea, the promontory was drilled. The carotid canal was
      unroofed to reveal the internal carotid artery. The minimum distance between the
      basal turn of the cochlea and the vertical part of the carotid canal was
      measured. RESULTS: The minimum distance between the basal turn of the cochlea and
      the carotid canal ranged from 0 to 3.9 mm (mean +/- SD, 1.3 +/- 0.8 mm). The
      carotid canal was abutting the basal turn of the cochlea in three cases, and
      impingement of the carotid canal on the anterior cochlear wall was found in five
      (8.6%) cases. CONCLUSION: Preoperative knowledge of findings like impingement
      (8.6%) and abutment (5.2%) of the carotid canal on the basal turn of the cochlea
      is of immense importance in cochlear implantation, which may otherwise lead to
      disastrous consequences during surgery.

PMID- 24945588
TI  - Response to pain management among patients with active cancer, no evidence of
      disease, or chronic nonmalignant pain in an outpatient palliative care clinic.
AB  - Abstract Background: Outpatient palliative care clinics may be required to manage
      patients not typically seen by palliative care. These include patients treated
      for cancer who no longer have evidence of disease (NED) and patients with chronic
      pain but no life-limiting illness (NLLI). Treatment response may differ among
      these groups. OBJECTIVES: Our aim was to determine treatment response by change
      in pain scores and morphine equivalent daily dose (MEDD) between initial visit
      and first follow-up in patients with active cancer (AC), NED, and those with
      NLLI. METHODS: A retrospective review of 143 consecutive outpatients referred to
      a clinic staffed by the palliative care program was conducted. Pain treatment
      response was defined by a >= 2 point difference on the Numerical Rating Scale
      (NRS) or >= 30% reduction from baseline score. RESULTS: Ninety-four patients had
      pain scores at both initial and follow-up visits after a median of 29.0 days.
      Fifty percent had AC, 27% NED, and 23% NLLI. Mean (standard deviation [SD]) pain
      scores at baseline were not significantly different among AC 6.0 (2.5), NED 5.6
      (2.5), and NLLI 6.8 (2.2) patients (p=0.22), but were significant at follow-up
      between AC 4.2 (2.7) and NLLI 6.0 (2.6) (p=0.03) groups. The percent of
      responders differed significantly between AC 57.4% and NED 20% groups (p=0.002).
      MEDD increased by 17.2 mg in AC, 40.9 mg in NED, and 18.1mg in NLLI patients
      (p=0.88).Benzodiazepine use was significantly more frequent in the NLLI group
      than the AC (p=0.025) and NED (p=0.002) groups. CONCLUSIONS: Although median pain
      scores improved at follow-up, less than half of patients were responders.
      Patients with AC had a significantly better response rate than NED patients and a
      lower pain score than NLLI patients at follow-up.

PMID- 24945589
TI  - From 2-aminomethyl-1,4-benzodioxane enantiomers to unichiral 2-cyano- and 2
      carbonyl-substituted benzodioxanes via dichloroamine.
AB  - 2-Substituted 1,4-benzodioxanes, such as 2-cyano-, 2-methoxycarbonyl-, 2
      aminocarbonyl-, and 2-formyl-1,4-benzodioxane, are key synthons that for the most
      part are never described as enantiomers or are inadequately characterized for
      enantiomeric purity. They were prepared by quantitative N,N-dichlorination of (R)
      and (S)-2-aminomethyl-1,4-benzodioxane and successive functional group
      conversions in high yields without any racemization of the stereogenic
      benzodioxane C(2). 

PMID- 24945590
TI  - Role of oxygen impurity on the mechanical stability and atomic cohesion of Ta3N5
      semiconductor photocatalyst.
AB  - Oxygen is a natural impurity in the Ta3N5 semiconductor photocatalyst and very
      difficult to be completely eliminated in different growth conditions. In this
      study, density functional theory calculations are performed to unravel the cause
      of natural existence of oxygen impurity in Ta3N5 from the perspectives of
      mechanical stability and atomic cohesion. The elastic properties calculations
      show that the oxygen impurity in Ta3N5 is able to remedy the weakened mechanical
      stability induced by the nitrogen vacancy in Ta3N5. The atomic cohesion
      calculations show that the oxygen impurity in Ta3N5 enlarges the valence band
      width of Ta3N5, suggesting that the oxygen impurity is able to strengthen the
      atomic cohesion of Ta3N5. Based on our calculation results, we propose that the
      charge-compensation codoping is a promising strategy to improve the water
      splitting ability of Ta3N5 and simultaneously maintain the mechanical stability
      and enhanced atomic cohesion of Ta3N5. 

PMID- 24945591
TI  - Minimally invasive surgery for endometrial cancer: does operative start time
      impact surgical and oncologic outcomes?
AB  - OBJECTIVE: Recent literature in ovarian cancer suggests differences in surgical
      outcomes depending on operative start time. We sought to examine the effects of
      operative start time on surgical outcomes for patients undergoing minimally
      invasive surgery for endometrial cancer. METHODS: A retrospective review was
      conducted of patients undergoing minimally invasive surgery for endometrial
      cancer at a single institution between 2000 and 2011. Surgical and oncologic
      outcomes were compared between patients with an operative start time before noon
      and those with a surgical start time after noon. RESULTS: A total of 380 patients
      were included in the study (245 with start times before noon and 135 with start
      times after noon). There was no difference in age (p=0.57), number of prior
      surgeries (p=0.28), medical comorbidities (p=0.19), or surgical complexity of the
      case (p=0.43). Patients with surgery starting before noon had lower median BMI
      than those beginning after noon, 31.2 vs. 35.3 respectively (p=0.01). No
      significant differences were observed for intraoperative complications (4.4% of
      patients after noon vs. 3.7% of patients before noon, p=0.79), estimated blood
      loss (median 100 cc vs. 100 cc, p=0.75), blood transfusion rates (7.4% vs. 8.2%,
      p=0.85), and conversion to laparotomy (12.6% vs. 7.4%, p=0.10). There was no
      difference in operative times between the two groups (198 min vs. 216.5 min,
      p=0.10). There was no association between operative start time and postoperative
      non-infectious complications (11.9% vs. 11.0%, p=0.87), or postoperative
      infections (17.8% vs. 12.3%, p=0.78). Length of hospital stay was longer for
      surgeries starting after noon (median 2 days vs. 1 day, p=0.005). No differences
      were observed in rates of cancer recurrence (12.6% vs. 8.8%, p=0.39), recurrence
      free survival (p=0.97), or overall survival (p=0.94). CONCLUSION: Our results
      indicate equivalent surgical outcomes and no increased risk of postoperative
      complications regardless of operative start time in minimally invasive
      endometrial cancer staging, despite longer length of hospital stay for surgeries
      beginning after noon.

PMID- 24945592
TI  - Comparison of triclosan and stannous fluoride dentifrices on parameters of
      gingival inflammation and plaque scores: a systematic review and meta-analysis.
AB  - OBJECTIVE: To systematically review the literature to compare the efficacy of
      triclosan (Tcs) and stannous fluoride (SnF) dentifrices on parameters of
      gingivitis and plaque scores. MATERIALS AND METHODS: Medline, EMBASE and Cochrane
      Central Register of Controlled Trials were searched up to March 2013 to identify
      appropriate studies. Studies regarding self-performed manual brushing by adults
      with a minimum 4 weeks of follow-up were included. Primary outcomes were
      parameters of gingivitis. Secondary outcome was plaque score. RESULTS: Of 55
      publications, 11 met the eligibility criteria. Additionally, four unpublished
      papers were added after contacting the manufacturers of the leading brands. In
      total, 15 studies [10 medium term and five long term (>6 months)] were processed
      for data analysis. There was no difference in gingival index (or its
      modification) between the two types of dentifrice [DiffM-0.04, 95% confidence
      interval CI (-0.11; 0.04); P = 0.34]. The change in the average gingival bleeding
      score was significantly in favour of SnF [DiffM0.02, 95% CI (0.01; 0.02); P <
      0.00001]. Plaque scores demonstrated a statistical significant difference in
      favour of Tcs, according to Quigley-Hein Plaque Index (Q&H PI; DiffM-0.29, 95% CI
      [-0.45; -0.13]; P = 0.0004), but there was no difference according to Rustogi
      Modified Navy Plaque Index (RMNPI) [DiffM-0.09, 95% CI (-0.01; 0.18); P = 0.07].
      Long-term results supported these findings. CONCLUSIONS: In the context of
      inconclusive results for the primary outcome variable of gingival health, it can
      be concluded that there was a minor and most likely clinically insignificant
      difference between Tcs- and SnF-containing dentifrices. Meta-analysis of plaque
      score reduction was also inconclusive; whereas Tcs was more effective when
      assessed by the Q&H PI, it was not when scored with the RMNPI.

PMID- 24945593
TI  - Magnetocaloric effect and critical behavior in Pr0.5Sr0.5MnO3: an analysis of the
      validity of the Maxwell relation and the nature of the phase transitions.
AB  - The Maxwell relation, the Clausius-Clapeyron equation, and a non-iterative method
      to obtain the critical exponents have been used to characterize the
      magnetocaloric effect (MCE) and the nature of the phase transitions in
      Pr0.5Sr0.5MnO3, which undergoes a second-order paramagnetic to ferromagnetic (PM
      FM) transition at TC ~ 247 K, and a first-order ferromagnetic to
      antiferromagnetic (FM-AFM) transition at TN ~ 165 K. We find that around the
      second-order PM-FM transition, the MCE (as represented by the magnetic entropy
      change, DeltaSM) can be precisely determined from magnetization measurements
      using the Maxwell relation. However, around the first-order FM-AFM transition,
      values of DeltaSM calculated with the Maxwell relation deviate significantly from
      those calculated by the Clausius-Clapeyron equation at the magnetic field and
      temperature ranges where a conversion between the AFM and FM phases occurs. A
      detailed analysis of the critical exponents of the second-order PM-FM transition
      allows us to correlate the short-range type magnetic interactions with the MCE.
      Using the Arrott-Noakes equation of state with the appropriate values of the
      critical exponents, the field- and temperature-dependent magnetization [Formula:
      see text] curves, and hence the [Formula: see text] curves, have been simulated
      and compared with experimental data. A good agreement between the experimental
      and simulated data has been found in the vicinity of the Curie temperature TC,
      but a noticeable discrepancy is present for [Formula: see text]. This discrepancy
      arises mainly from the coexistence of AFM and FM phases and the presence of
      ferromagnetic clusters in the AFM matrix.

PMID- 24945594
TI  - Exciton localization and dissociation dynamics in CdS and CdS-Pt quantum confined
      nanorods: effect of nonuniform rod diameters.
AB  - One-dimensional colloidal multicomponent semiconductor nanorods, such as CdSe-CdS
      dot-in-rod, have been extensively studied as a promising class of new materials
      for solar energy conversion because of the possibilities of using the band
      alignment of component materials and the rod-diameter-dependent quantum
      confinement effect to control the location of electrons and holes and to
      incorporate catalysts through the growth of Pt tips. Here we used CdS nanorods as
      an example to study the effect of nonuniform diameters along the rod on the
      exciton localization and dissociation dynamics in CdS and (platinum tipped) CdS
      Pt nanorods. We showed that, in CdS nanorods prepared by seeded growth, the
      presence of a bulb with a larger diameter around the CdS seed resulted in an
      additional absorption band lower in energy than the exciton in the CdS rod. As a
      result, excitons generated in the CdS rod could undergo ultrafast localization to
      the bulb region in addition to trapping on the CdS rod. We observed that the Pt
      tip led to fast exciton dissociation by electron transfer. However, excitons
      localized on the CdS bulb showed slower average ET rates than those localized in
      the rod region. Our findings suggested that the effect of rod morphology should
      be carefully considered in designing multicomponent nanorods for solar energy
      conversion applications. 

PMID- 24945595
TI  - Histone deacetylase inhibitor induces the expression of select epithelial genes
      in mouse utricle sensory epithelia-derived progenitor cells.
AB  - Mouse utricle sensory epithelial cell-derived progenitor cells (MUCs), which have
      hair cell progenitor and mesenchymal features via epithelial-to-mesenchymal
      transition (EMT) as previously described, provide a potential approach for hair
      cell regeneration via cell transplantation. In this study, we treated MUCs with
      trichostatin A (TSA) to determine whether histone deacetylase inhibitor is able
      to stimulate the expression of epithelial genes in MUCs, an essential step for
      guiding mesenchymal-like MUCs to become sensory epithelial cells. After 72 h of
      TSA treatment, MUCs acquired epithelial-like features, which were indicated by
      increased expression of epithelial markers such as Cdh1, Krt18, and Dsp.
      Additionally, TSA decreased the expression of mesenchymal markers, including
      Zeb1, Zeb2, Snai1, and Snai2, and prosensory genes Lfng, Six1, and Dlx5.
      Moreover, the expression of the hair cell genes Atoh1 and Myo6 was increased in
      TSA-treated MUCs. We also observed significantly decreased expression of Hdac2
      and Hdac3 in TSA-treated MUCs. However, no remarkable change was detected in
      protein expression using immunofluorescence, indicating that TSA-induced HDAC
      inhibition may contribute to the initial stage of the mesenchymal-to-epithelial
      phenotypic change. In the future, more work is needed to induce hair cell
      regeneration using inner ear tissue-derived progenitors to achieve an entire
      mesenchymal-to-epithelial transition.

PMID- 24945596
TI  - Influence of FcgammaRIIIb polymorphism on its ability to cooperate with
      FcgammaRIIa and CR3 in mediating the oxidative burst of human neutrophils.
AB  - Considering that human neutrophil FcgammaRIIa and FcgammaRIIIb receptors interact
      synergistically with CR3 in triggering neutrophil functional responses, allelic
      polymorphisms in these receptors might influence such interactions. We assessed
      whether FcgammaRIIIb polymorphisms affect FcgammaR/CR cooperation in mediating
      the neutrophil oxidative burst (OB), in particular the FcgammaRIIIb/CR3
      cooperation that occurs via lectin-saccharide-like interactions. The OB of human
      neutrophil antigen (HNA)-1a-, HNA-1b-, and HNA-1a/-1b-neutrophils stimulated with
      immune complexes, opsonized or not with serum complement, was measured by the
      luminol-enhanced chemiluminescence assay. Compared with HNA-1a-neutrophils, HNA
      1b-neutrophils exhibited reduced FcgammaR-stimulated OB, but increased
      FcgammaR/CR-stimulated OB. It suggests that (i) FcgammaR and CR cooperate more
      effectively in HNA-1b-neutrophils, and (ii) the HNA-1b allotype influences the
      FcgammaRIIIb cooperation with FcgammaRIIa, but not with CR3. HNA-1a- and HNA-1b
      neutrophils exhibited similar OB responses elicited via CR3 alone or via
      FcgammaR/CR-independent pathways. In addition, the level of FcgammaRIIIb,
      FcgammaRIIa, and CR3 expression did not differ significantly among the neutrophil
      groups studied. Together, these results demonstrate that the HNA-1b allotype
      influences the functional cooperation between FcgammaRIIIb and FcgammaRIIa, and
      suggest that the difference in the glycosylation pattern between HNA-1a and HNA
      1b does not affect the FcgammaRIIIb cooperation with CR3. 

PMID- 24945597
TI  - Allicin protects rat cardiomyoblasts (H9c2 cells) from hydrogen peroxide-induced
      oxidative injury through inhibiting the generation of intracellular reactive
      oxygen species.
AB  - Oxidative stress is considered an important factor that promotes cell death in
      response to a variety of pathophysiological conditions. This study investigated
      the antioxidant properties of allicin, the principle ingredient of garlic, on
      preventing oxidative stress-induced injury. The antioxidant capacities of allicin
      were measured by using 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging
      assay and hydrogen peroxide (H(2)O(2))-induced cell damage on H9c2
      cardiomyoblasts. Allicin (0.3-10 MUM) pre-incubation could concentration
      dependently attenuate the intracellular reactive oxygen species (ROS) increase
      induced by H(2)O(2) on H9c2 cells. It could also protect H9c2 cells against
      H(2)O(2)-induced cell damage. However, the DPPH free radical scavenging activity
      of allicin was shown to be low. Therefore, it is believed that the protective
      effect of allicin on H9c2 cells could inhibit intracellular ROS production
      instead of scavenging extracellular H(2)O(2) or free radicals. For the observed
      protective effect on H9c2 cells, allicin might also be effective in reducing free
      radical-induced myocardial cell death in ischemic condition.

PMID- 24945598
TI  - Acute zonal occult outer retinopathy: a classification based on multimodal
      imaging.
AB  - IMPORTANCE: We describe the multimodal imaging in a group of patients showing a
      distinct clinical entity that best represents acute zonal occult outer
      retinopathy (AZOOR). OBJECTIVE: To propose a classification of AZOOR based on
      clinical fundus and multimodal imaging. DESIGN, SETTING AND PARTICIPANTS: A
      retrospective review of patients diagnosed as having AZOOR at 2 centers. After
      reviewing more than 400 cases diagnosed or referred to us as AZOOR or AZOOR
      complex, we assembled 30 cases that fit our current definition; (48 eyes) with a
      median age at diagnosis of 47 years (age range, 17-86 years) and a mean follow-up
      period of 39 months. Twenty patients were female. Eighteen patients had initially
      been seen with bilateral lesions, mostly asymmetric (4 cases were symmetric).
      Most patients had no remarkable medical or ocular history. The median visual
      acuity at the time of presentation was 20/25 (range, 20/20 to 20/400). MAIN
      OUTCOMES AND MEASURES: Multimodal imaging, including fundus photography,
      fluorescein and indocyanine green angiography, fundus autofluorescence imaging,
      and corresponding eye-tracked spectral-domain coherence tomography imaging.
      RESULTS: Each patient was initially seen with visual symptoms of photopsia and
      scotoma, and most had a detectable lesion in the fundus evident clinically or
      detected on multimodal imaging. The clinical appearance of the AZOOR lesions
      varied depending on their duration and location, but some features were
      characteristic, including a demarcating line of the progression at the level of
      the outer retina and a trizonal pattern of sequential involvement of the outer
      retina, retinal pigment epithelium, and choroid, as well as frequent zonal
      progression. Advanced cases of AZOOR demonstrated disruption of the inner and
      outer retina and severe damage or loss of the retinal pigment epithelium and the
      choroid. CONCLUSIONS AND RELEVANCE: A specific definition of AZOOR based on
      multimodal imaging is proposed to help physicians distinguish it from other
      diseases of the posterior fundus, including white spot syndromes and autoimmune,
      hereditary, paraneoplastic, toxic, and other inflammatory retinopathies.

PMID- 24945599
TI  - Human health impacts of antibiotic use in agriculture: A push for improved causal
      inference.
AB  - Resistant bacterial infections in humans continue to pose a significant challenge
      globally. Antibiotic use in agriculture contributes to this problem, but failing
      to appreciate the relative importance of diverse potential causes represents a
      significant barrier to effective intervention. Standard epidemiologic methods
      alone are often insufficient to accurately describe the relationships between
      agricultural antibiotic use and resistance. The integration of diverse
      methodologies from multiple disciplines will be essential, including causal
      network modeling and population dynamics approaches. Because intuition can be a
      poor guide in directing investigative efforts of these non-linear and
      interconnected systems, integration of modeling efforts with empirical
      epidemiology and microbiology in an iterative process may result in more valuable
      information than either in isolation. 

PMID- 24945600
TI  - Natural gas fugitive emissions rates constrained by global atmospheric methane
      and ethane.
AB  - The amount of methane emissions released by the natural gas (NG) industry is a
      critical and uncertain value for various industry and policy decisions, such as
      for determining the climate implications of using NG over coal. Previous studies
      have estimated fugitive emissions rates (FER)--the fraction of produced NG
      (mainly methane and ethane) escaped to the atmosphere--between 1 and 9%. Most of
      these studies rely on few and outdated measurements, and some may represent only
      temporal/regional NG industry snapshots. This study estimates NG industry
      representative FER using global atmospheric methane and ethane measurements over
      three decades, and literature ranges of (i) tracer gas atmospheric lifetimes,
      (ii) non-NG source estimates, and (iii) fossil fuel fugitive gas hydrocarbon
      compositions. The modeling suggests an upper bound global average FER of 5%
      during 2006-2011, and a most likely FER of 2-4% since 2000, trending downward.
      These results do not account for highly uncertain natural hydrocarbon seepage,
      which could lower the FER. Further emissions reductions by the NG industry may be
      needed to ensure climate benefits over coal during the next few decades.

PMID- 24945601
TI  - Intranasally administered mesenchymal stem cells promote a regenerative niche for
      repair of neonatal ischemic brain injury.
AB  - Previous work from our group has shown that intranasal MSC-treatment decreases
      lesion volume and improves motor and cognitive behavior after hypoxic-ischemic
      (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC
      migration after intranasal administration, and the early effects of MSCs on
      neurogenic processes and gliosis at the lesion site. HI brain injury was induced
      in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The
      kinetics of MSC migration were investigated by immunofluorescence and MRI
      analysis. BDNF and NGF gene expression was determined by qPCR analysis following
      MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and
      M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry
      analyses showed that MSCs reach the lesion site already within 2h after
      intranasal administration. At 12h after administration the number of MSCs at the
      lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells
      increased 1 to 3days after MSC administration in the SVZ. At the lesion,
      GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment.
      The number of NeuN(+) cells increased within 5days, leading to a dramatic
      regeneration of the somatosensory cortex and hippocampus at 18days after
      intranasal MSC administration. Interestingly, MSCs expressed significantly more
      BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment
      resulted in the resolution of the glial scar surrounding the lesion, represented
      by a decrease in reactive astrocytes and microglia and polarization of microglia
      towards the M2 phenotype. In view of the current lack of therapeutic strategies,
      we propose that intranasal MSC administration is a powerful therapeutic option
      through its functional repair of the lesion represented by regeneration of the
      cortical and hippocampal structure and decrease of gliosis. 

PMID- 24945602
TI  - Healthcare utilization following mild traumatic brain injury in female veterans.
AB  - BACKGROUND: Mild traumatic brain injury (TBI) is a significant problem for
      Veterans. Gender differences in mild TBI outcomes such as return-to-work,
      resolution of symptoms and mental health diagnoses have been reported. The
      purpose of the study is to characterize gender differences in VA healthcare
      utilization in the year following mild TBI diagnosis. METHODS: This was a
      retrospective database study of 12 144 Veterans diagnosed with mild TBI in fiscal
      year 2008 and their healthcare utilization in the following year. RESULTS: The
      mean age was 43.6 +/- 17 and the majority were men (94.1%). Overall, women had
      more outpatient utilization than men with mild TBI (mean: 48 vs. 37 visits; p <=
      0.001). Adjusted analyses indicated that women had a rate of outpatient
      utilization 25% higher than men (IRR = 1.25, 95% CI = 1.17-1.33). It was found
      that 13.6% of the difference in outpatient utilization by gender could be
      explained by other factors such as race, age, marital status, geographic location
      and illness burden. CONCLUSION: Male Veterans had less outpatient utilization
      than females in the year following mild TBI diagnosis. Gender and other factors
      only accounted for a small portion of the differences observed; therefore, gender
      only partially accounts for differences in healthcare utilization following mild
      TBI.

PMID- 24945603
TI  - Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by
      means of inflammatory cells.
AB  - Choukroun's platelet-rich fibrin (PRF) is obtained from blood without adding
      anticoagulants. In this study, protocols for standard platelet-rich fibrin (S
      PRF) (2700 rpm, 12 minutes) and advanced platelet-rich fibrin (A-PRF) (1500 rpm,
      14 minutes) were compared to establish by histological cell detection and
      histomorphometrical measurement of cell distribution the effects of the
      centrifugal force (speed and time) on the distribution of cells relevant for
      wound healing and tissue regeneration. Immunohistochemistry for monocytes, T and
      B -lymphocytes, neutrophilic granulocytes, CD34-positive stem cells, and
      platelets was performed on clots produced from four different human donors.
      Platelets were detected throughout the clot in both groups, although in the A-PRF
      group, more platelets were found in the distal part, away from the buffy coat
      (BC). T- and B-lymphocytes, stem cells, and monocytes were detected in the
      surroundings of the BC in both groups. Decreasing the rpm while increasing the
      centrifugation time in the A-PRF group gave an enhanced presence of neutrophilic
      granulocytes in the distal part of the clot. In the S-PRF group, neutrophils were
      found mostly at the red blood cell (RBC)-BC interface. Neutrophilic granulocytes
      contribute to monocyte differentiation into macrophages. Accordingly, a higher
      presence of these cells might be able to influence the differentiation of host
      macrophages and macrophages within the clot after implantation. Thus, A-PRF might
      influence bone and soft tissue regeneration, especially through the presence of
      monocytes/macrophages and their growth factors. The relevance and feasibility of
      this tissue-engineering concept have to be proven through in vivo studies. 

PMID- 24945605
TI  - Abortion services for sex workers in Uganda: successful strategies in an urban
      clinic.
AB  - Sex workers' need for safe abortion services in Uganda is greater than that of
      the population of women of reproductive age because of their number of sexual
      contacts, the inconsistent use of contraception and their increased risk of
      forced sex, rape or other forms of physical and sexual violence. We sought to
      understand sex workers' experiences with induced abortion services or post
      abortion care (PAC) at an urban clinic in Uganda. We conducted nine in-depth
      interviews with sex workers. All in-depth interviews were audiotaped,
      transcribed, translated, computer recorded and coded for analysis. We identified
      several important programmatic considerations for safe abortion services for sex
      workers. Most important is creating community-level interventions in which women
      can speak openly about abortion, creating a support network among sex workers,
      training peer educators, and making available a community outreach educator and
      community outreach workshops on abortion. At the health facility, it is important
      for service providers to treat sex workers with care and respect, allow sex
      workers to be accompanied to the health facility and guarantee confidentiality.
      These programmatic elements help sex workers to access safe abortion services and
      should be tried with all women of reproductive age to improve women's access to
      safe abortion in Uganda. 

PMID- 24945604
TI  - Structural studies of the spinosyn forosaminyltransferase, SpnP.
AB  - Spinosyns A and D (spinosad) are complex polyketide natural products
      biosynthesized through the cooperation of a modular polyketide synthase and
      several tailoring enzymes. SpnP catalyzes the final tailoring step, transferring
      forosamine from a TDP-D-forosamine donor substrate to a spinosyn pseudoaglycone
      acceptor substrate. Sequence analysis indicated that SpnP belongs to a small
      group of glycosyltransferases (GTs) that require an auxiliary protein for
      activation. However, unlike other GTs in this subgroup, no putative auxiliary
      protein gene could be located in the biosynthetic gene cluster. To learn more
      about SpnP, the structures of SpnP and its complex with TDP were determined to
      2.50 and 3.15 A resolution, respectively. Binding of TDP causes the reordering of
      several residues in the donor substrate pocket. SpnP possesses a structural
      feature that has only been previously observed in the related glycosyltransferase
      EryCIII, in which it mediates association with the auxiliary protein EryCII. This
      motif, H-X-R-X5-D-X5-R-X12-20-D-P-X3-W-L-X12-18-E-X4-G, may be predictive of
      glycosyltransferases that interact with an auxiliary protein. A reverse glycosyl
      transfer assay demonstrated that SpnP possesses measurable activity in the
      absence of an auxiliary protein. Our data suggest that SpnP can bind its donor
      substrate by itself but that the glycosyl transfer reaction is facilitated by an
      auxiliary protein that aids in the correct folding of a flexible loop surrounding
      the pseudoaglycone acceptor substrate-binding pocket.

PMID- 24945606
TI  - Osteoblastic differentiation under controlled bioactive ion release by silica and
      titania doped sodium-free calcium phosphate-based glass.
AB  - Sodium-free phosphate-based glasses (PGs) doped with both SiO2 and TiO2 (50P2O5
      40CaO-xSiO2-(10-x)TiO2, where x=10, 7, 5, 3, and 0mol%) were developed and
      characterised for controlled ion release applications in bone tissue engineering.
      Substituting SiO2 with TiO2 directly increased PG density and glass transition
      temperature, indicating a cross-linking effect of Ti on the glass network which
      was reflected by significantly reduced degradation rates in an aqueous
      environment. X-ray diffraction confirmed the presence of Ti(P2O7) in crystallised
      TiO2-containing PGs, and nuclear magnetic resonance showed an increase in Q(1)
      phosphate species with increasing TiO2 content. Substitution of SiO2 with TiO2
      also reduced hydrophilicity and surface energy. In biological assays, MC3T3-E1
      pre-osteoblasts effectively adhered to the surface of PG discs and the
      incorporation of TiO2, and hence higher stability of the PG network,
      significantly increased cell viability and metabolic activity indicating the
      biocompatibility of the PGs. Addition of SiO2 increased ionic release from the
      PG, which stimulated alkaline phosphatase (ALP) activity in MC3T3-E1 cells upon
      ion exposure. The incorporation of 3mol% TiO2 was required to stabilise the PG
      network against unfavourable rapid degradation in aqueous environments. However,
      ALP activity was greatest in PGs doped with 5-7mol% SiO2 due to up-regulation of
      ionic concentrations. Thus, the properties of PGs can be readily controlled by
      modifying the extent of Si and Ti doping in order to optimise ion release and
      osteoblastic differentiation for bone tissue engineering applications. 

PMID- 24945607
TI  - Cefuroxime axetil loaded solid lipid nanoparticles for enhanced activity against
      S. aureus biofilm.
AB  - The present research work is focused on the development of solid lipid
      nanoparticles of cefuroxime axetil (CA-SLN) for its enhanced inhibitory activity
      against Staphylococcus aureus produced biofilm. CA-SLN was prepared by solvent
      emulsification/evaporation method using single lipid (stearic acid (SA)) and
      binary lipids (SA and tristearin (TS)). Process variables such as volume of
      dispersion medium, concentration of surfactant, homogenization speed and time
      were optimized. The prepared SLN were characterized for encapsulation efficiency,
      drug polymer interaction studies (DSC and FT-IR), shape and surface morphology
      (SEM and AFM), in vitro drug release, stability studies and in vitro anti biofilm
      activity against S. aureus biofilm. Among the process variables, increased volume
      of dispersion medium, homogenization speed and time led to increase in particle
      size whereas increase in surfactant concentration decreased the particle size.
      SLN prepared using binary lipids exhibited higher entrapment efficiency than the
      single lipid. DSC and FT-IR studies showed no incompatible interaction between
      drug and excipients. CA-SLN showed two folds higher anti-biofilm activity in
      vitro than pristine CA against S. aureus biofilm. 

PMID- 24945608
TI  - Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.
AB  - For decades researchers have been targeting prevention of Rhodococcus equi
      (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding
      industry has supported the ongoing efforts by researchers to develop a safe and
      cost effective vaccine to prevent disease in foals. Traditional vaccines
      including live, killed and attenuated (physical and chemical) vaccines have
      proved to be ineffective and more modern molecular-based vaccines including the
      DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate
      protection of foals. Newer, bacterial vector vaccines have recently shown promise
      for R. equi in the mouse model. This article describes the findings of key
      research in R. equi vaccine development and looks at alternative methods that may
      potentially be utilised.

PMID- 24945609
TI  - Cyclic alkyl(amino) carbene stabilized biradical of disilicontetrachloride.
AB  - One and a half decades ago the formation of Si2Cl4 from the intermediate species
      SiCl2 was theoretically predicted to be exothermic. The hypothetical Si2Cl4 has
      never been experimentally synthesized and isolated. Herein, we report that the
      Si2Cl4 species was stabilized as singlet biradical (Cy-cAAC.)2Si2Cl4 utilizing
      two cAAC (cyclic alkyl(amino) carbene). This compound is stable, isolable, and
      storable at rt under an inert atmosphere. The electronic structure and bonding
      were studied by theoretical calculations which revealed that the molecule
      possesses a singlet biradical ground state with an unpaired electron on each
      carbene C atom having opposite spin. 

PMID- 24945610
TI  - Gene expression responses in human lung fibroblasts exposed to alpha particle
      radiation.
AB  - This study examined alpha (alpha-) particle radiation effects on global changes
      in gene expression for the purposes of identifying potential signaling pathways
      that may be involved in Radon ((222)Rn) gas exposure and lung carcinogenesis.
      Human lung fibroblast cells were exposed to alpha-particle radiation at a dose
      range of 0-1.5Gy. Twenty-four hours post-exposure, transcript modulations were
      monitored using microarray technology. A total of 208 genes were shown to be dose
      responsive (FDR adjusted p<0.05, Fold change>|2|) of which 32% were upregulated
      and 68% downregulated. Fourteen of the high expressing genes (>|4| fold) were
      further validated using alternate technology and among these genes, GDF15 and
      FGF2 were assessed at the protein level. GDF15, a known marker of lung injury,
      had expression levels 3-fold higher in exposed cell culture media, 24h post
      irradiation as detected by ELISA. Further, pathway analysis of the dose
      responsive transcripts showed them to be involved in biological processes related
      to cell cycle control/mitosis, chromosome instability and cell differentiation.
      This panel of genes with particular focus on GDF15 may merit further analysis to
      determine their specific role in mechanisms leading to alpha-particle induced
      lung carcinogenesis.

PMID- 24945612
TI  - Antimicrobial stewardship: another focus for patient safety?
AB  - PURPOSE OF REVIEW: This review describes the overlapping aspects of antimicrobial
      stewardship and patient-safety initiatives and justifies why stewardship belongs
      under the umbrella of patient safety. RECENT FINDINGS: Addressing the continued
      emergence of antibiotic resistance through the discovery of new drugs is not a
      sustainable strategy, particularly as antibiotics are increasingly more difficult
      and costly to develop. Thus, it is essential that we preserve the utility of
      existing antibiotics. Antimicrobial stewardship programs can assist with
      achieving this goal. Currently, however, the term 'antimicrobial stewardship' is
      generally not easily understood by regulators, hospital administrators, or the
      public. Perhaps more clout would be given to antimicrobial stewardship if it is
      associated with safety. In this review, we present concrete examples of how
      antimicrobial stewardship programs can focus on achieving goals already
      recognized as essential for patient safety. SUMMARY: Patient safety is an
      integral component of antimicrobial stewardship. To make the concept of
      antimicrobial stewardship more palatable, the association between antimicrobial
      stewardship and safety needs to be emphasized.

PMID- 24945611
TI  - Priming by chemokines restricts lateral mobility of the adhesion receptor LFA-1
      and restores adhesion to ICAM-1 nano-aggregates on human mature dendritic cells.
AB  - LFA-1 is a leukocyte specific beta2 integrin that plays a major role in
      regulating adhesion and migration of different immune cells. Recent data suggest
      that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible
      anchor during homing of DCs through the afferent lymphatics into the lymph nodes,
      by transiently switching its molecular conformational state. However, the role of
      LFA-1 mobility in this process is not yet known, despite that the importance of
      lateral organization and dynamics for LFA-1-mediated adhesion regulation is
      broadly recognized. Using single particle tracking approaches we here show that
      LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid
      chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a
      significant reduction of mobility and an increase on the fraction of stationary
      receptors, consistent with re-activation of the receptor. Addition of soluble
      monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of
      LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further
      reduced LFA-1 mobility and readily bound to the receptor. Overall, our results
      emphasize the importance of LFA-1 lateral mobility across the membrane on the
      regulation of integrin activation and its function as adhesion receptor.
      Importantly, our data show that chemokines alone are not sufficient to trigger
      the high affinity state of the integrin based on the strict definition that
      affinity refers to the adhesion capacity of a single receptor to its ligand in
      solution. Instead our data indicate that nanoclustering of the receptor, induced
      by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1
      high affinity state is transiently triggered by inside-out signals. 

PMID- 24945614
TI  - Immunizations following solid-organ transplantation.
AB  - PURPOSE OF REVIEW: To highlight the latest evidence for the use of key vaccines
      that are recommended in organ transplant candidates and recipients. RECENT
      FINDINGS: Influenza vaccine is the best studied vaccine; factors affecting
      immunogenicity of this vaccine include time from transplant, use of mycophenolate
      mofetil and type of transplant. Newer formulations of influenza vaccine are
      available, but data for these are limited. Updated recommendations include giving
      conjugated pneumococcal vaccine to adult transplant candidates and recipients
      followed by the polysaccharide vaccine to increase serotype coverage. Human
      papillomavirus vaccine should also be given to transplant recipients, although
      the immunogenicity may be suboptimal. Quadrivalent meningococcal conjugate
      vaccine needs to be given in special circumstances such as to patients who are
      starting eculizumab therapy. Live vaccines in general are contraindicated,
      although increasing safety data are emerging for Varicella vaccine. Herpes Zoster
      vaccine may be offered prior to transplant, although the utility of this strategy
      regarding protection from shingles after transplant is not known. Newer vaccines
      such as inactivated zoster vaccine and vaccines for the prevention of
      cytomegalovirus are under study. SUMMARY: Immunization for organ transplant
      recipients is an important part of pretransplant evaluation and the long-term
      care of the transplant recipient.

PMID- 24945615
TI  - Improving ventilator-associated event surveillance in the National Healthcare
      Safety Network and addressing knowledge gaps: update and review.
AB  - PURPOSE OF REVIEW: The Centers for Disease Control and Prevention (CDC) recently
      transitioned from ventilator-associated pneumonia (VAP) surveillance to
      ventilator-associated event (VAE) surveillance in adult inpatient settings. Since
      the transition, several modifications have been made to improve surveillance
      methods, and there is a growing body of data regarding the epidemiology, risk
      factors, and preventability of VAEs. RECENT FINDINGS: The VAE surveillance
      definition algorithm is based on objective criteria and includes three tiers:
      ventilator-associated conditions, infection-related ventilator-associated
      complications, and possible and probable VAP. VAE surveillance expands the
      purview of surveillance beyond pneumonia alone to include additional
      complications of mechanical ventilation. Most VAEs are caused by pneumonia,
      pulmonary edema, atelectasis, or acute respiratory distress syndrome. VAEs are
      associated with adverse outcomes including prolonged mechanical ventilation,
      longer intensive care and hospital length-of-stay, and higher mortality rates.
      Studies to date suggest that minimizing sedation and optimizing fluid management
      can reduce VAE rates. SUMMARY: We review the CDC's recent updates on VAE
      surveillance definitions, methods, and tools, and provide an overview of the
      growing evidence base for VAE as a patient safety measure. Further work is needed
      to affirm and extend the current knowledge about how best to prevent VAEs.

PMID- 24945617
TI  - Do topical products reduce postincision scars?

PMID- 24945613
TI  - Back to basics: hand hygiene and isolation.
AB  - PURPOSE OF REVIEW: Hand hygiene and isolation are basic, but very effective,
      means of preventing the spread of pathogens in healthcare. Although the principle
      may be straightforward, this review highlights some of the controversies
      regarding the implementation and efficacy of these interventions. RECENT
      FINDINGS: Hand hygiene compliance is an accepted measure of quality and safety in
      many countries. The evidence for the efficacy of hand hygiene in directly
      reducing rates of hospital-acquired infections has strengthened in recent years,
      particularly in terms of reduced rates of staphylococcal sepsis. Defining the key
      components of effective implementation strategies and the ideal method(s) of
      assessing hand hygiene compliance are dependent on a range of factors associated
      with the healthcare system. Although patient isolation continues to be an
      important strategy, particularly in outbreaks, it also has some limitations and
      can be associated with negative effects. Recent detailed molecular epidemiology
      studies of key healthcare-acquired pathogens have questioned the true efficacy of
      isolation, alone as an effective method for the routine prevention of disease
      transmission. SUMMARY: Hand hygiene and isolation are key components of basic
      infection control. Recent insights into the benefits, limitations and even
      adverse effects of these interventions are important for their optimal
      implementation.

PMID- 24945616
TI  - Experimental studies of H13CO+ recombining with electrons at energies between 2
      50,000 meV.
AB  - An investigation into the dissociative recombination process for H(13)CO(+) using
      merged ion-electron beam methods has been performed at the heavy ion storage ring
      CRYRING, Stockholm, Sweden. We have measured the branching fractions of the
      different product channels at ~ 0 eV collision energy to be the following: CO + H
      87 +/- 2%, OH + C 9 +/- 2%, and O + CH 4 +/- 2%. The formation of electronically
      excited CO in the dominant reaction channel has also been studied, and we report
      the following tentative branching fractions for the different CO product
      electronic states: CO(X (1)Sigma(+)) + H, 54 +/- 10%; CO(a (3)Pi) + H, 23 +/- 4%;
      and CO(a' (3)Sigma(+)) + H, 23 +/- 4%. The absolute cross section between ~ 2-50
      000 meV was measured and showed resonance structures between 3 and 15 eV. The
      cross section was fitted in the energy range relevant to astrophysics, i.e.,
      between 1 and 300 meV, and was found to follow the expression sigma = 1.3 +/- 0.3
      * 10(-16) E(-1.29 +/- 0.05) cm(2) and the corresponding thermal rate constant was
      determined to be k(T) = 2.0 +/- 0.4 * 10(-7)(T/300)(-0.79 +/- 0.05) cm(3) s(-1).
      Radioastronomical observations with the IRAM 30 m telescope of HCO(+) toward the
      Red Rectangle yielded an upper column density limit of 4 * 10(11) cm(-2) of
      HCO(+) at the 1sigma level in that object, indicating that previous claims that
      the dissociative recombination of HCO(+) plays an important role in the
      production of excited CO molecules emitting the observed Cameron bands in that
      object are not supported.

PMID- 24945618
TI  - Concurrent Uveal and Vitreoretinal Lymphoma Masquerading as Anterior Uveitis.

PMID- 24945619
TI  - Risk assessment of applicators to chlorpyrifos through dermal contact and
      inhalation at different maize plant heights in China.
AB  - Dermal and respiratory exposure assessments and risk assessment for applicators
      were performed with 48% chlorpyrifos EC. The chlorpyrifos was applied with lever
      operated knapsacks under three spraying environments, namely, average maize field
      heights of 62 cm (A1), 108 cm (A2), and 212 cm (A3). The whole body dosimetry
      technique was applied to collect dermal exposure samples including cotton
      protective garments, gloves, socks, and hats. A personal air monitor equipped
      with an XAD-2 resin was used for respiratory exposure assessment. Without
      personal protective equipment (PPE) the total potential dermal exposure (PDE) was
      27.8, 90.6, and 462.1 mL h(-1) under A1, A2, and A3 spraying environments,
      respectively. In addition, with the change in the maize plant height, the major
      exposure parts on the applicators were also different. Under single-layer garment
      and glove protection circumstances, internal dermal exposure (IDE) was 3.37 mL h(
      1) for A1, 4.28 mL h(-1) for A2, and 18.32 mL h(-1) for A3. Potential inhalation
      exposure (PIE) was detected in A3, but it was not detected in A1 and A2. For risk
      assessment, the margin of safety (MOS) was calculated from the PDE or IDE and
      PIE. The MOS values for the three spraying environments were <1 under no PPE and
      single-layer garment and glove protection circumstances, indicating high
      possibility of health risk. However, with double protective garments, the MOS
      values for A1 and A2 cases were all >1, but the MOS was <1 in the A3 case. 

PMID- 24945620
TI  - Some current issues in the design of HIV noninferiority trials.
AB  - Since the introduction of protease inhibitors and their combination with two
      nucleoside reverse transcriptase inhibitors in tri-therapy, there has been a
      continuous improvement in the efficacy of antiretroviral treatments. Such
      combinations have been rendered even more effective by the introduction of non
      nucleoside reverse transcriptase inhibitors and, more recently, integrase
      inhibitors. This progress has led to a move away from superiority designs towards
      noninferiority designs for randomized clinical trials for HIV. Noninferiority
      trials aim to demonstrate that a new regimen is no worse than the current
      standard. The methodological issues associated with such designs have been
      discussed, but recent HIV trials provide us with an opportunity to consider the
      choice of hypotheses. Recent HIV trials have been overpowered, due to the
      assumption of lower success rates than observed and the enrollment of a large
      number of patients. The use of stratified statistical methods for primary
      endpoint analysis, with sample size calculated by classical methods (without
      stratification), also increases the statistical power. Some HIV trials have a
      statistical power close to 99%. Surprisingly, the results of some previous
      studies or phase II trials are not taken into account when designing the
      corresponding phase III trials. We discuss alternative hypotheses and designs. 

PMID- 24945621
TI  - A prospective, randomised, double-blind, placebo-controlled study to examine the
      effectiveness of burst spinal cord stimulation patterns for the treatment of
      failed back surgery syndrome.
AB  - OBJECTIVES: Spinal cord stimulation (SCS) for the treatment of chronic pain is a
      well-established therapy. However, the requirement that paresthesia be
      continually felt by the patient has important downsides. This study evaluated the
      effectiveness of a new paresthesia-free SCS paradigm, called burst stimulation,
      for the treatment of failed back surgery syndrome (FBSS) with a prospective,
      randomized, double-blind, placebo-controlled design. MATERIALS AND METHODS:
      Twenty patients with FBSS and a preexisting SCS system each received three
      treatment allocations in random order for a period of one week: 500-Hz tonic
      stimulation, burst stimulation, and placebo stimulation. The primary outcome
      measure was pain intensity measured on a numerical rating scale (NRS). Secondary
      outcome measures were pain quality measured using the Short-Form McGill Pain
      Questionnaire (SFMPQ) and safety. Additional data were collected relating to pain
      related disability measured using the Oswestry Disability Index (ODI). RESULTS:
      The lowest mean NRS and SFMPQ scores were observed under burst stimulation. For
      the burst stimulation treatment group, mean NRS and SFMPQ scores were
      significantly decreased compared with the other treatment groups. Mean NRS and
      SFMPQ scores were not significantly different between 500-Hz tonic stimulation
      and placebo stimulation. Although the lowest mean ODI score was observed under
      burst stimulation, no significant differences were found between the ODI
      categories. No adverse events occurred, and burst stimulation was significantly
      preferred by 16 patients (80%). CONCLUSIONS: Overall, burst stimulation resulted
      in significantly better pain relief and improved pain quality in the short term
      compared with 500-Hz tonic stimulation and placebo stimulation and was preferred
      by the majority of patients.

PMID- 24945622
TI  - Understanding the sub-cellular dynamics of silicon transportation and synthesis
      in diatoms using population-level data and computational optimization.
AB  - Controlled synthesis of silicon is a major challenge in nanotechnology and
      material science. Diatoms, the unicellular algae, are an inspiring example of
      silica biosynthesis, producing complex and delicate nano-structures. This happens
      in several cell compartments, including cytoplasm and silica deposition vesicle
      (SDV). Considering the low concentration of silicic acid in oceans, cells have
      developed silicon transporter proteins (SIT). Moreover, cells change the level of
      active SITs during one cell cycle, likely as a response to the level of external
      nutrients and internal deposition rates. Despite this topic being of fundamental
      interest, the intracellular dynamics of nutrients and cell regulation strategies
      remain poorly understood. One reason is the difficulties in measurements and
      manipulation of these mechanisms at such small scales, and even when possible,
      data often contain large errors. Therefore, using computational techniques seems
      inevitable. We have constructed a mathematical model for silicon dynamics in the
      diatom Thalassiosira pseudonana in four compartments: external environment,
      cytoplasm, SDV and deposited silica. The model builds on mass conservation and
      Michaelis-Menten kinetics as mass transport equations. In order to find the free
      parameters of the model from sparse, noisy experimental data, an optimization
      technique (global and local search), together with enzyme related penalty terms,
      has been applied. We have connected population-level data to individual-cell
      level quantities including the effect of early division of non-synchronized
      cells. Our model is robust, proven by sensitivity and perturbation analysis, and
      predicts dynamics of intracellular nutrients and enzymes in different
      compartments. The model produces different uptake regimes, previously recognized
      as surge, externally-controlled and internally-controlled uptakes. Finally, we
      imposed a flux of SITs to the model and compared it with previous classical
      kinetics. The model introduced can be generalized in order to analyze different
      biomineralizing organisms and to test different chemical pathways only by
      switching the system of mass transport equations. 

PMID- 24945623
TI  - Identification of late larval stage developmental checkpoints in Caenorhabditis
      elegans regulated by insulin/IGF and steroid hormone signaling pathways.
AB  - Organisms in the wild develop with varying food availability. During periods of
      nutritional scarcity, development may slow or arrest until conditions improve.
      The ability to modulate developmental programs in response to poor nutritional
      conditions requires a means of sensing the changing nutritional environment and
      limiting tissue growth. The mechanisms by which organisms accomplish this
      adaptation are not well understood. We sought to study this question by examining
      the effects of nutrient deprivation on Caenorhabditis elegans development during
      the late larval stages, L3 and L4, a period of extensive tissue growth and
      morphogenesis. By removing animals from food at different times, we show here
      that specific checkpoints exist in the early L3 and early L4 stages that
      systemically arrest the development of diverse tissues and cellular processes.
      These checkpoints occur once in each larval stage after molting and prior to
      initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like
      growth factor receptor, regulates passage through the L3 and L4 checkpoints in
      response to nutrition. The FOXO transcription factor DAF-16, a major target of
      insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin)
      to arrest developmental upon nutrient removal. The effects of DAF-16 on
      progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450
      ortholog involved in the production of C. elegans steroid hormones. Our results
      identify a novel mode of C. elegans growth in which development progresses from
      one checkpoint to the next. At each checkpoint, nutritional conditions determine
      whether animals remain arrested or continue development to the next checkpoint. 

PMID- 24945626
TI  - Multiplexing determination of small cell lung cancer biomarkers and their
      isovariants in serum by immunocapture LC-MS/MS.
AB  - A multiplex method for the determination of the small cell lung cancer (SCLC)
      markers progastrin releasing peptide (ProGRP) and neuron specific enolase (NSE)
      is presented, which involves coextraction by immunoaffinity (IA) beads and
      codetermination by selected reaction monitoring (SRM). The performance was
      compared with two IA SRM methods which were recently validated for individual
      marker determination. The multiplexing method reduces sample volume, handling
      time per sample, and reagent consumption and shows good linearity, recovery,
      quantitative measurements, and sensitivity with lower limit of detection (LLOD)
      values of 7.2 pM (=90 pg/mL) and 4.5 pM (=210 pg/mL) and lower limit of
      quantitation (LLOQ) values of 24 pM (=300 pg/mL) and 15 pM (=700 pg/mL), for
      total ProGRP and gamma-NSE, respectively. The novel aspect of this approach is
      the multiplexing of ProGRP and NSE with the additional ability to perform
      fingerprinting by the selective determination of ProGRP isoform 1, ProGRP isoform
      3, and total ProGRP, as well as the alpha- and the gamma-subunit of NSE
      isoenzymes. Six serum samples from patients with SCLC were analyzed to
      demonstrate the methods feasibility to simultaneously differ between and
      individually quantify ProGRP, NSE, and their isoform and isoenzyme variants,
      respectively. Both the presence of and variation between all the isoforms and
      isoenzymes, as well as covarying results with the conventional immunometric
      assays for total ProGRP and gamma-NSE, were seen in the analyses of patient serum
      samples. 

PMID- 24945627
TI  - The use of a novel bone allograft wash process to generate a biocompatible,
      mechanically stable and osteoinductive biological scaffold for use in bone tissue
      engineering.
AB  - Fresh-frozen biological allograft remains the most effective substitute for the
      'gold standard' autograft, sharing many of its osteogenic properties but,
      conversely, lacking viable osteogenic cells. Tissue engineering offers the
      opportunity to improve the osseointegration of this material through the addition
      of mesenchymal stem cells (MSCs). However, the presence of dead, immunogenic and
      potentially harmful bone marrow could hinder cell adhesion and differentiation,
      graft augmentation and incorporation, and wash procedures are therefore being
      utilized to remove the marrow, thereby improving the material's safety. To this
      end, we assessed the efficiency of a novel wash technique to produce a
      biocompatible, biological scaffold void of cellular material that was
      mechanically stable and had osteoinductive potential. The outcomes of our
      investigations demonstrated the efficient removal of marrow components (~99.6%),
      resulting in a biocompatible material with conserved biomechanical stability.
      Additionally, the scaffold was able to induce osteogenic differentiation of MSCs,
      with increases in osteogenic gene expression observed following extended culture.
      This study demonstrates the efficiency of the novel wash process and the
      potential of the resultant biological material to serve as a scaffold in bone
      allograft tissue engineering.

PMID- 24945624
TI  - The glycosylated Rv1860 protein of Mycobacterium tuberculosis inhibits dendritic
      cell mediated TH1 and TH17 polarization of T cells and abrogates protective
      immunity conferred by BCG.
AB  - We previously reported interferon gamma secretion by human CD4+ and CD8+ T cells
      in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium
      tuberculosis (MTB) as well as protection of guinea pigs against a challenge with
      virulent MTB following prime-boost immunization with DNA vaccine and poxvirus
      expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG
      (BCG-SSI) recombinant expressing MTB Rv1860 (BCG-TB1860) showed loss of
      protective ability compared to the parent BCG strain expressing the control GFP
      protein (BCG-GFP). Since Rv1860 is a secreted mannosylated protein of MTB and
      BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG
      GFP, BCG-TB1860 effected a significant near total reduction both in secretion of
      cytokines IL-2, IL-12p40, IL-12p70, TNF-alpha, IL-6 and IL-10, and up regulation
      of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone
      marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-beta
      unchanged. These effects were mimicked by BCG-TB1860His which carried a 6
      Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG
      TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not
      by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG
      TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN
      gamma and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI
      showed significantly less proliferation and secretion of IL-2, IFN-gamma and IL
      17, but secreted higher levels of IL-10 in response to in vitro restimulation
      with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860
      also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF
      alpha compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their
      deleterious effects on DC may thus contribute to suppress the generation of a TH1
      and TH17-dominated adaptive immune response that is vital for protection against
      tuberculosis.

PMID- 24945628
TI  - Impact of illiteracy on depression symptomatology in community-dwelling older
      adults.
AB  - BACKGROUND: In many countries, illiteracy rates among aged people are quite high.
      However, only few studies have specifically investigated the impact of illiteracy
      on depression. METHODS: Data for 1,890 elderly individuals (aged >=65 years) were
      obtained from a nationwide dementia epidemiological study conducted in South
      Korea. Based on their reading ability, the participants were divided into three
      groups: totally illiterate, partially illiterate, and literate. The Korean
      version of the Geriatric Depression Scale - Short Form (SGDS-K) was used to
      detect depression (cut-off score = 8). Multivariate logistic regression analyses
      were used to assess the association between illiteracy and depression. To explore
      clinical features of depression in illiterate people, we performed logistic
      regression to calculate odds ratios of positive responses (or negative responses
      to reverse-coded items) for each SGDS-K item using literate individuals as the
      reference group. RESULTS: Totally illiterate participants had 2.41 times the odds
      and partially illiterate individuals had 1.59 times the odds of being depressed
      compared with literate participants after controlling for other variables.
      Compared with literate individuals, illiterate elderly persons were at increased
      odds for responding negatively to the majority of SGDS-K items, including "having
      memory problems," "others are better off than me," and "feeling worthless" even
      after controlling for various demographic and clinical factors. CONCLUSIONS:
      Illiteracy in elderly individuals was associated with a higher rate and increased
      severity of depression. Illiteracy negatively affected depression symptomatology,
      especially factors associated with self-esteem. Therefore, clinicians should
      carefully monitor for the presence of depression in illiterate elderly adults.

PMID- 24945629
TI  - Insights into embryo defenses of the invasive apple snail Pomacea canaliculata:
      egg mass ingestion affects rat intestine morphology and growth.
AB  - BACKGROUND: The spread of the invasive snail Pomacea canaliculata is expanding
      the rat lungworm disease beyond its native range. Their toxic eggs have virtually
      no predators and unusual defenses including a neurotoxic lectin and a proteinase
      inhibitor, presumably advertised by a warning coloration. We explored the effect
      of egg perivitellin fluid (PVF) ingestion on the rat small intestine morphology
      and physiology. METHODOLOGY/PRINCIPAL FINDINGS: Through a combination of
      biochemical, histochemical, histopathological, scanning electron microscopy, cell
      culture and feeding experiments, we analyzed intestinal morphology, growth rate,
      hemaglutinating activity, cytotoxicity and cell proliferation after oral
      administration of PVF to rats. PVF adversely affects small intestine metabolism
      and morphology and consequently the standard growth rate, presumably by lectin
      like proteins, as suggested by PVF hemaglutinating activity and its cytotoxic
      effect on Caco-2 cell culture. Short-term effects of ingested PVF were studied in
      growing rats. PVF-supplemented diet induced the appearance of shorter and wider
      villi as well as fused villi. This was associated with changes in glycoconjugate
      expression, increased cell proliferation at crypt base, and hypertrophic mucosal
      growth. This resulted in a decreased absorptive surface after 3 days of treatment
      and a diminished rat growth rate that reverted to normal after the fourth day of
      treatment. Longer exposure to PVF induced a time-dependent lengthening of the
      small intestine while switching to a control diet restored intestine length and
      morphology after 4 days. CONCLUSIONS/SIGNIFICANCE: Ingestion of PVF rapidly
      limits the ability of potential predators to absorb nutrients by inducing large,
      reversible changes in intestinal morphology and growth rate. The occurrence of
      toxins that affect intestinal morphology and absorption is a strategy against
      predation not recognized among animals before. Remarkably, this defense is rather
      similar to the toxic effect of plant antipredator strategies. This defense
      mechanism may explain the near absence of predators of apple snail eggs.

PMID- 24945630
TI  - Use of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS) in young
      adult women.
AB  - BACKGROUND: Validated measures that can accurate describe young adults' HPV
      vaccination attitudes and how these relate to vaccination intention and receipt
      are needed for developing interventions to improve low HPV vaccination levels.
      The Carolina HPV Immunization Attitudes Scale (CHIAS) is a validated measure of
      these outcomes that was originally designed for parents. OBJECTIVE: To assess the
      performance of the CHIAS among young adult women using an exploratory factor
      analysis. METHODS: A convenience sample of 139 young adult women (age 18-26
      years) were given the CHIAS measure at baseline. Factor analysis was used to
      determine attitudinal factor groupings and the association of these factors with
      HPV vaccination intention. A 6-month follow up assessment examined the stability
      of the CHIAS over time and the association of baseline vaccine factors with
      vaccine receipt. RESULTS: Five factors loaded on to the CHIAS in young adults -
      "Barriers," "Harms," "Effectiveness," "Risk Denial" and "Uncertainty," - which
      was similar to the factor loadings of CHIAS for parents. "Harms" was the factor
      most consistently associated with vaccination intention at all time points
      assessed. Only 5 women had received or made an appointment to receive the vaccine
      at the 6-month follow-up. CONCLUSIONS: In terms of categorizing HPV vaccination
      attitudes, the CHIAS appears to have similar performance among young adults as in
      parents. However, additional studies are needed to assess the utility of the
      CHIAS for predicting HPV vaccine receipt among the young adult population.

PMID- 24945631
TI  - Wolbachia transcription elongation factor "Wol GreA" interacts with
      alpha2betabeta'sigma subunits of RNA polymerase through its dimeric C-terminal
      domain.
AB  - OBJECTIVES: Wolbachia, an endosymbiont of filarial nematode, is considered a
      promising target for therapy against lymphatic filariasis. Transcription
      elongation factor GreA is an essential factor that mediates transcriptional
      transition from abortive initiation to productive elongation by stimulating the
      escape of RNA polymerase (RNAP) from native prokaryotic promoters. Upon screening
      of 6257 essential bacterial genes, 57 were suggested as potential future drug
      targets, and GreA is among these. The current study emphasized the
      characterization of Wol GreA with its domains. METHODOLOGY/PRINCIPAL FINDINGS:
      Biophysical characterization of Wol GreA with its N-terminal domain (NTD) and C
      terminal domain (CTD) was performed with fluorimetry, size exclusion
      chromatography, and chemical cross-linking. Filter trap and far western blotting
      were used to determine the domain responsible for the interaction with
      alpha2betabeta'sigma subunits of RNAP. Protein-protein docking studies were done
      to explore residual interaction of RNAP with Wol GreA. The factor and its domains
      were found to be biochemically active. Size exclusion and chemical cross-linking
      studies revealed that Wol GreA and CTD exist in a dimeric conformation while NTD
      subsists in monomeric conformation. Asp120, Val121, Ser122, Lys123, and Ser134
      are the residues of CTD through which monomers of Wol GreA interact and shape
      into a dimeric conformation. Filter trap, far western blotting, and protein
      protein docking studies revealed that dimeric CTD of Wol GreA through Lys82,
      Ser98, Asp104, Ser105, Glu106, Tyr109, Glu116, Asp120, Val121, Ser122, Ser127,
      Ser129, Lys140, Glu143, Val147, Ser151, Glu153, and Phe163 residues exclusively
      participates in binding with alpha2betabeta'sigma subunits of polymerase.
      CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this research is the
      first documentation of the residual mode of action in wolbachial mutualist.
      Therefore, findings may be crucial to understanding the transcription mechanism
      of this alpha-proteobacteria and in deciphering the role of Wol GreA in filarial
      development.

PMID- 24945633
TI  - Phalloplasty with an innervated island pedicled anterolateral thigh flap in a
      female-to-male transsexual.
AB  - Since 2001, we have been performing phalloplasty with a radial forearm free flap
      as the flap of first choice in female-to-male transsexuals (FTMTS). In the
      present case, a 22-year-old FTMTS with a negative Allen test, we achieved good
      results by performing phalloplasty with an innervated island pedicled
      anterolateral thigh flap using the "tube within a tube" technique, in which the
      penis and urethra are constructed with a single flap. As compared to a forearm
      flap, use of an innervated island-pedicled flap may have the following advantages
      in phalloplasty: 1) no need for a microsurgical technique; 2) no scars at
      noticeable sites; 3) small functional loss in the flap donor area; 4) no
      sacrifice of major blood vessels. Thus, this technique seems to be a useful
      clinical alternative for phallic reconstruction.

PMID- 24945632
TI  - The association between serum 25-hydroxyvitamin D concentrations and depressive
      symptoms in Korean adults: findings from the fifth Korea National Health and
      Nutrition Examination Survey 2010.
AB  - The aims of this study were to examine the association between circulating
      vitamin D (25(OH)D) levels and depressive symptoms and to evaluate the
      associations between depressive symptoms and various sociodemographic factors.
      Data on serum 25(OH)D levels, sociodemographic factors, and information on
      depressive symptoms were obtained from the Korea National Health and Nutrition
      Examination Survey V-1 2010. A total of 3,570 Koreans aged >=20 years were
      included in the statistical analysis. Subjects with depressive symptoms had lower
      serum levels of 25(OH)D (41.6+/-16.2 nmol/L) than those without (44.3+/-16.2
      nmol/L; P-value<0.05; effect size = 0.17). In a logistic regression analysis, the
      25(OH)D sufficiency group (>=50 nmol/L) revealed fewer depressive symptoms (OR,
      0.72; 95% CI, 0.53-0.97; P-value = 0.032) after adjusting for multiple factors.
      In addition, females (OR, 3.61; 95% CI, 2.55-5.11; P-value<0.001), problematic
      alcohol users (OR, 2.33; 95% CI, 1.63-3.34; P-value<0.001), current smokers (OR,
      1.43; 95% CI, 1.02-1.99; P-value = 0.036), and subjects who experienced weight
      loss (OR, 1.78; 95% CI, 1.30-2.44; P-value<0.001) were more likely to answer
      "yes" on question for depressive symptoms. In conclusion, low serum levels of
      25(OH)D were associated with an increased risk for depression symptoms in Korean
      adults. In addition, several sociodemographic factors were related to the
      depressive symptoms. Our results provide insight into the relationships among
      vitamin D status, sociodemographic factors, and depression in the Korean
      population. 

PMID- 24945634
TI  - Anticoagulation for the initial treatment of venous thromboembolism in patients
      with cancer.
AB  - BACKGROUND: Compared with patients without cancer, patients with cancer who
      receive anticoagulant treatment for venous thromboembolism (VTE) are more likely
      to develop recurrent VTE. OBJECTIVES: To compare the efficacy and safety of three
      types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin
      (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the
      initial treatment of VTE in patients with cancer. SEARCH METHODS: A comprehensive
      search for studies of anticoagulation in patients with cancer including a
      February 2013 electronic search of: the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science. SELECTION CRITERIA:
      Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in
      patients with cancer and objectively confirmed VTE. DATA COLLECTION AND ANALYSIS:
      Using a standardized data form, review authors extracted data in duplicate on
      methodologic quality, participants, interventions, and outcomes of interest that
      included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic
      syndrome, quality of life, and thrombocytopenia. MAIN RESULTS: Of 9559 identified
      citations, 16 RCTs were eligible: 13 compared LMWH with UFH, two compared
      fondaparinux with heparin, and one compared dalteparin with tinzaparin. Meta
      analysis of 11 studies showed a statistically significant reduction in mortality
      at three months of follow-up with LMWH compared with UFH (risk ratio (RR) 0.71;
      95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect
      estimate after excluding studies of lower methodologic quality (RR 0.72; 95% CI
      0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no
      statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to
      2.08). The overall quality of evidence was low for LMWH versus UFH due to
      imprecision and likely publication bias. There were no statistically significant
      differences between heparin and fondaparinux for the outcomes of mortality (RR
      1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major
      bleeding (RR 0.79; 95% CI 0.39 to1.63), or minor bleeding (RR 1.50; 95% CI 0.87
      to 2.59). The one study comparing dalteparin with tinzaparin found no
      statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).
      AUTHORS' CONCLUSIONS: LMWH is possibly superior to UFH in the initial treatment
      of VTE in patients with cancer. Additional trials focusing on patient-important
      outcomes will further inform the questions addressed in this review.

PMID- 24945636
TI  - Do sororities promote members' health? A study of memorable messages regarding
      weight and appearance.
AB  - This study examines the relationship between sorority communication practices and
      members' body images through the lens of organizational socialization and
      identification. Specifically, we analyzed 210 sorority members' memorable
      messages concerning weight and physical appearance using an inductive coding
      method. While many of the messages examined were affirming or complimentary in
      nature, the results of the analysis suggest that these types of messages may
      positively as well as negatively influence members' body images, behaviors
      regarding physical appearance, and social identities. These findings contribute
      to scholarly and practical understandings of the influences on college women's
      body image and health and the potentially powerful role that organizations play
      in shaping members' attitudes and actions concerning their eating, exercise, and
      other aspects of their appearance. Implications for future health communication
      research in other organizational contexts outside of sororities are also
      discussed. Additionally, the findings of the current study indicate the broad
      utility of a memorable messages approach and suggest the need for further
      examination of the ways in which differing organizational dynamics may
      demonstrate divergence from traditional sources of memorable messages. 

PMID- 24945637
TI  - A comparative study on phenolic components and biological activity of some
      Senecio species in Turkey.
AB  - OBJECTIVE: The phenolic components and biological activity of nine Senecio
      species growing in Turkey were investigated. METHODS: Senecio species were
      extracted with methanol. The content of total phenols was determined using Folin
      Ciocalteu method, while individual phenolic acids and flavonoids were detected
      using HPLC analysis. Also, to determine the antioxidant capacity,
      phosphomolybdenum assay and 1,1-diphenyl picrylhydrazyl (DPPH) radical-scavenging
      activity assay were used. Antimicrobial activity of extract was determined using
      agar diffusion and broth microdilution method. KEY FINDINGS: The total phenolic
      contents of the extracts were found to be highest in Senecio cilicius and Senecio
      mollis extracts (117.45 and 113.40 mg equivalent to gallic acid/g, respectively).
      S. salsuginea showed the strongest free radical-scavenging activity with IC50
      (the concentration providing 50% inhibition) = 26.23 MUg/ml and S. mollis showed
      the highest antioxidant capacity in the phosphomolybdenum method (434.48 mg
      equivalent to ascorbic acid/g). The extracts exerted promising antibacterial
      activity against most of the test bacteria (minimal inhibitory concentration =
      6.25-12.5 mg/ml), but no activity was observed against Candida albicans.
      CONCLUSION: The results demonstrated that nine Senecio species possess high
      antioxidant and antimicrobial activity in accordance with the high amount of
      phenolic contents in the extracts that might be natural agencies used in many
      areas such as food, pharmacy and alternative medicine.

PMID- 24945635
TI  - Barrier to auto integration factor becomes dephosphorylated during HSV-1
      Infection and Can Act as a host defense by impairing viral DNA replication and
      gene expression.
AB  - BAF (Barrier to Autointegration Factor) is a highly conserved DNA binding protein
      that senses poxviral DNA in the cytoplasm and tightly binds to the viral genome
      to interfere with DNA replication and transcription. To counteract BAF, a
      poxviral-encoded protein kinase phosphorylates BAF, which renders BAF unable to
      bind DNA and allows efficient viral replication to occur. Herein, we examined how
      BAF phosphorylation is affected by herpes simplex virus type 1 (HSV-1) infection
      and tested the ability of BAF to interfere with HSV-1 productive infection.
      Interestingly, we found that BAF phosphorylation decreases markedly following HSV
      1 infection. To determine whether dephosphorylated BAF impacts HSV-1 productive
      infection, we employed cell lines stably expressing a constitutively
      unphosphorylated form of BAF (BAF-MAAAQ) and cells overexpressing wild type (wt)
      BAF for comparison. Although HSV-1 production in cells overexpressing wtBAF was
      similar to that in cells expressing no additional BAF, viral growth was reduced
      approximately 80% in the presence of BAF-MAAAQ. Experiments were also performed
      to determine the mechanism of the antiviral activity of BAF with the following
      results. BAF-MAAAQ was localized to the nucleus, whereas wtBAF was dispersed
      throughout cells prior to infection. Following infection, wtBAF becomes
      dephosphorylated and relocalized to the nucleus. Additionally, BAF was associated
      with the HSV-1 genome during infection, with BAF-MAAAQ associated to a greater
      extent than wtBAF. Importantly, unphosphorylated BAF inhibited both viral DNA
      replication and gene expression. For example, expression of two regulatory
      proteins, ICP0 and VP16, were substantially reduced in cells expressing BAF
      MAAAQ. However, other viral genes were not dramatically affected suggesting that
      expression of certain viral genes can be differentially regulated by
      unphosphorylated BAF. Collectively, these results suggest that BAF can act in a
      phosphorylation-regulated manner to impair HSV-1 transcription and/or DNA
      replication, which is similar to the antiviral activity of BAF during vaccinia
      infection. 

PMID- 24945638
TI  - Metabolomic analysis using porcine skin: a pilot study of analytical techniques.
AB  - BACKGROUND: Metabolic byproducts serve as indicators of the chemical processes
      and can provide valuable information on pathogenesis by measuring the amplified
      output. Standardized techniques for metabolome extraction of skin samples serve
      as a critical foundation to this field but have not been developed. OBJECTIVES:
      We sought to determine the optimal cell lysage techniques for skin sample
      preparation and to compare GC-TOF-MS and UHPLC-QTOF-MS for metabolomic analysis.
      METHODS: Using porcine skin samples, we pulverized the skin via various
      combinations of mechanical techniques for cell lysage. After extraction, the
      samples were subjected to GC-TOF-MS and/or UHPLC-QTOF-MS. RESULTS: Signal
      intensities from GC-TOF-MS analysis showed that ultrasonication (2.7x107) was
      most effective for cell lysage when compared to mortar-and-pestle (2.6x107), ball
      mill followed by ultrasonication (1.6x107), mortar-and-pestle followed by
      ultrasonication (1.4x107), and homogenization (trial 1: 8.4x106; trial 2:
      1.6x107). Due to the similar signal intensities, ultrasonication and mortar-and
      pestle were applied to additional samples and subjected to GC-TOF-MS and UHPLC
      QTOF-MS. Ultrasonication yielded greater signal intensities than mortar-and
      pestle for 92% of detected metabolites following GC-TOF-MS and for 68% of
      detected metabolites following UHPLC-QTOF-MS. CONCLUSION: Overall,
      ultrasonication is the preferred method for efficient cell lysage of skin tissue
      for both metabolomic platforms. With standardized sample preparation, metabolomic
      analysis of skin can serve as a powerful tool in elucidating underlying
      biological processes in dermatological conditions.

PMID- 24945639
TI  - The economic burden of sunscreen usage.
AB  - Excessive sun exposure is known to be the leading cause of skin cancer. The
      direct cellular damage inflicted by the ultraviolet (UV) radiation from the sun
      results in premature aging, DNA damage, and mutations that ultimately lead to
      skin cancer. Sunscreens are highly recommended to protect against UV radiation.
      However, little research has been conducted on the economic burden of sunscreen
      use. In this study, we aimed to evaluate the annual cost of sunscreen under both
      ideal and actual use conditions while stratifying for the sun protection factor
      (SPF) and by the name brand or equivalent store brand sunscreen. Pricing data was
      collected for sunscreens of SPF 30, 50, 70, and 100. For each type of sunscreen,
      the size and price of the container were recorded. Our results demonstrated that
      sunscreen prices increased with SPF but purchasing a generic sunscreen resulted
      in savings of 40%-50%. Our estimates reveal that sunscreens are affordable with
      annual expenditures ranging from $30.21 to $61.94, depending on brand, for SPF 50
      sunscreens used with minimal application density for the average person. 

PMID- 24945640
TI  - Cantharidin: a comprehensive review of the clinical literature.
AB  - BACKGROUND: Cantharidin is a topical vesicant that causes intraepidermal
      acantholysis with clinical application that includes the removal of warts,
      molluscum contagiosum (MC), calluses, and acquired perforating dermatoses.
      OBJECTIVE: To provide a comprehensive literature review of the efficacy and
      safety of cantharidin in the management of various cutaneous conditions. METHODS:
      A PubMed search was conducted using the term "cantharidin" combined with "warts",
      "plantar warts", "verruca vulgaris", "periungal", "subungual", "topical
      treatment", "topical therapy for warts", molluscum contagiosum", "perforating
      collagenosis," and "acantholysis." RESULTS: A total of 749 articles were
      identified and 37 articles met inclusion criteria for this review. The majority
      of studies show that cantharidin is an effective and safe treatment for removal
      of warts and MC. Several studies also show potential novel applications of
      cantharidin in acquired perforating dermatosis, acute herpes zoster, and
      leishmaniasis. Adverse effects are generally mild but common and should be
      monitored, particularly in the pediatric population. LIMITATIONS: There is a
      paucity of high-powered clinical studies involving the use of cantharidin.
      CONCLUSION: Topical cantharidin is a safe and effective treatment for warts,
      molluscum contagiosum, and callus removal, with promising uses in perforating
      dermatoses and leishmaniasis.

PMID- 24945641
TI  - Dermatology on YouTube.
AB  - YouTube, reaches upwards of six billion users on a monthly basis and is a unique
      source of information distribution and communication. Although the influence of
      YouTube on personal health decision-making is well established, this study
      assessed the type of content and viewership on a broad scope of dermatology
      related content on YouTube. Select terms (i.e. dermatology, sun protection, skin
      cancer, skin cancer awareness, and skin conditions) were searched on YouTube.
      Overall, the results included 100 videos with over 47 million viewers. Advocacy
      was the most prevalent content type at 24% of the total search results. These 100
      videos were "shared" a total of 101,173 times and have driven 6,325 subscriptions
      to distinct YouTube user pages. Of the total videos, 35% were uploaded by or
      featured an MD/DO/PhD in dermatology or other specialty/field, 2% FNP/PA, 1% RN,
      and 62% other. As one of the most trafficked global sites on the Internet,
      YouTube is a valuable resource for dermatologists, physicians in other
      specialties, and the general public to share their dermatology-related content
      and gain subscribers. However, challenges of accessing and determining evidence
      based data remain an issue.

PMID- 24945642
TI  - Primary cutaneous zygomycosis secondary to minor trauma in an immunocompromised
      pediatric patient: a case report.
AB  - Zygomycosis is an opportunistic infection generally found in immunocompromised
      individuals. Herein we present a pediatric patient with primary cutaneous
      mucormycosis that developed at a site of trauma. Diagnosis and treatment are
      discussed.

PMID- 24945643
TI  - Multimodal therapy of idiopathic pyoderma gangrenosum.
AB  - A 13-year old girl was admitted to the University of California Davis Medical
      Center for evaluation and treatment of cutaneous bullae and ulcerations over her
      lower extremities that were refractory to antibiotic therapy and incision and
      drainage. Her disease continued to worsen with the appearance of multiple new
      bullae and the progression of old ones into deep ulcers with undermined borders.
      Biopsy revealed a neutrophilic dermatosis and diagnostic work-up was negative for
      infectious or autoimmune etiologies. Given her clinical presentation, biopsy
      results, and negative work-up, a diagnosis of pyoderma gangrenosum (PG) was made
      and she was started on immunosuppressive medications. The patient was started on
      a multidrug regimen of prednisone and cyclosporine but remission was not achieved
      until the addition of adalimumab. After the inflammatory component of her disease
      was under control, wound care measures were maximized to promote ulcer healing.
      Wound care measures included compression and debridement. Upon complete closure
      of all wounds she was successfully transitioned to mycophenolate mofetil
      monotherapy for maintenance therapy. This case emphasizes the need for
      combinational therapy to successfully treat severe cases of PG, which are often
      refractory to monotherapy with prednisone or cyclosporine. It also highlights the
      importance of appropriate wound care to achieve complete ulcer healing.

PMID- 24945644
TI  - Unilateral nevoid telangiectasia syndrome (UNTS) associated with chronic
      hepatitis C virus and positive immunoreactivity for VEGF.
AB  - Unilateral Nevoid Telangectasia Syndrome (UNTS) is characterized by superficial
      telangiectasias in a unilateral distribution. Vascular endothelial growth factor
      (VEGF) may play a role in the pathogenesis of UNTS in patients with underlying
      hepatic disease. We report a case of a patient with UNTS accompanied by chronic
      hepatitis C virus infection, with a normal serum estrogen profile and strong
      positive immunohistochemical staining of lesional skin with VEGF.

PMID- 24945645
TI  - Application of bimatoprost ophthalmic solution 0.03% for the treatment of eyebrow
      hypotrichosis: series of ten cases.
AB  - In December 2008, bimatoprost ophthalmic solution 0.03% was approved in the
      United States for the treatment of hypotrichosis of the eyelashes. Since then,
      there have been several reports in the literature on the off-label use of
      bimatoprost ophthalmic solution 0.03% for the treatment of thinning in other hair
      bearing areas, such as in the eyebrows and in the scalp. Herein, a prospective
      pilot study is presented in which bimatoprost ophthalmic solution 0.03% is
      evaluated for helping to re-grow hair in the eyebrow region of ten female
      patients.

PMID- 24945646
TI  - Cutaneous thrombogenic vasculopathy associated with bevacizumab therapy.
AB  - Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth
      factor (VEGF), is an angiogenesis inhibitor used to treat a variety of cancers,
      including lung, colon, cervical, ovarian, and renal cancers as well as
      glioblastoma. A significant adverse effect associated with its use is one of
      thromboembolic events. We report a case of a 74-year-old male with diagnosis of
      glioblastoma multiforme treated with partial resection, radiation, temozolomide,
      and bevacizumab. He presented to a plastic surgeon with a several week history of
      asymptomatic crusted hemorrhagic ulcers and purpuric patches on the lower legs
      shortly following the initiation of bevacizumab. A biopsy showed an occlusive
      pauci-inflammatory thrombogenic vasculopathy associated with ischemic epidermal
      and dermal changes and accompanied by extensive vascular C5b-9 (complement C5b-9
      membrane attack complex) deposition. Bevacizumab has been associated with
      thrombotic complications including atypical hemolytic uremic syndrome and
      arterial and venous thrombosis. C5b-9 may be the factor most important in the
      mechanism of vascular thrombosis given the extent of deposition in our index
      case. Thrombotic events in the skin associated with bevacizumab therapy are
      without precedent and dermatologists should be aware of this potential
      complication.

PMID- 24945647
TI  - Mycobacterium fortuitum infection arising in a new tattoo.
AB  - We report an uncommon case of a cutaneous infection with Mycobacterium fortuitum
      arising in a new tattoo. A 29-year-old man presented with a several month history
      of a non-pruritic papular eruption within a tattoo; the papules developed 1-to-2
      weeks after the tattoo procedure. He denied similar symptoms with previous
      tattoos. He had been treated unsuccessfully with cephalexin. Histopathologic
      examination revealed perifollicular chronic and granulomatous inflammation,
      consistent with chronic folliculitis. Acid-fast bacilli culture identified
      Mycobacterium fortuitum complex. The patient was treated with a 2-month course of
      oral trimethoprim-sulfamethoxazole (160mg/800mg twice daily) and ciprofloxacin
      (250 mg twice daily), with clinical improvement at follow up after three weeks of
      the antibiotic regimen. Rapidly growing mycobacteria have emerged as a cause of
      tattoo-associated cutaneous infection in recent years. Diagnosis and treatment
      can be difficult without clinical suspicion. M. fortuitum and other rapidly
      growing mycobacteria should be considered in the differential diagnosis of tattoo
      associated dermatologic complications. 

PMID- 24945648
TI  - Mycobacterium chelonae infection presenting as recurrent cutaneous and
      subcutaneous nodules--a presentation previously diagnosed as Weber Christian
      disease.
AB  - Although the dermatologic community rarely uses "Weber-Christian Disease" as a
      diagnosis, it still appears in the internal medicine literature. Herein we
      present a patient with recurrent cutaneous and subcutaneous nodules who was
      initially treated with aggressive immunosupression for a presumptive diagnosis of
      Weber-Christian Disease. After more than a decade the patient was diagnosed with
      cutaneous Mycobacterium chelonea. This case is an excellent example of the
      difficulty in diagnosing mycobacterial infections and underscores the importance
      of having a high suspicion for infectious etiologies for unresponsive cutaneous
      eruptions in patients on immunosuppressive medications.

PMID- 24945649
TI  - Porokeratosis ptychotropica: a rare variant of porokeratosis.
AB  - BACKGROUND: Porokeratosis, a well recognized disorder of keratinization, is known
      to have several clinical variants. This report describes a rare variant
      characterized by verrucous plaques. METHODS: An adult male presented with a
      slowly progressive verrucous plaque on the gluteal region that was resistant to
      conventional therapy. Careful inspection revealed a keratotic ridge at the plaque
      border leading to the diagnosis. RESULTS: Histopathology showed the presence of
      multiple cornoid lamellae confirming the diagnosis of porokeratosis
      ptychotropica. CONCLUSIONS: Porokeratosis ptychotropica is a rare variant of
      porokeratosis with fewer than 25 cases described in the literature. This report
      is to highlight the importance of considering this particular entity in the
      diagnosis of genitogluteal plaques, especially those not responding to
      conventional modalities.

PMID- 24945650
TI  - Adult onset unilateral systematized porokeratotic eccrine ostial and dermal duct
      nevus: a case report.
AB  - Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon,
      benign dermatosis that is characterized by asymptomatic grouped keratotic papules
      and plaques with a linear pattern on the extremities with distinct porokeratotic
      histopathological features. The lesions usually appear at birth or in childhood,
      although rare cases of late-onset adult PEODDN have been described. Herein we
      report a case of adult onset PEODDN with unilateral and segmental involvement. 

PMID- 24945651
TI  - Recurrent paraneoplastic wells syndrome in a patient with metastatic renal cell
      cancer.
AB  - A 58-year-old man with a history of hyperlipidemia and hypertension presented to
      the dermatology clinic with a 3-month history of a sudden onset, progressively
      worsening pruritic eruption involving the torso and extremities. Prior treatment
      included azithromycin and oral and intramuscular steroids, without improvement.
      Laboratory results demonstrated a serum eosinophil count of 7x10(3)/uL (normal 0
      4). A 4-mm punch biopsy of the plaque on the patient's left thigh revealed a
      diffuse dermatitis with innumerable eosinophils with formation of "flame
      figures." Histologically, these findings are consistent with a diagnosis of Wells
      syndrome (WS). A work up for possible underlying malignancy found that the
      patient had underlying clear cell renal carcinoma. The eruption largely resolved
      following right laparoscopic nephrectomy with negative surgical margins, thus
      confirming the diagnosis of paraneoplastic WS. However, 2 years later the patient
      developed metastasis to his liver, lungs, and ribs. The patient's cancer has
      continued to progress despite treatment with high-dose interleukin-2, oral
      sunitinib, afinitor. avastin, azacytidine, and currently axitinib. Our case is
      the first to describe eosinophilic cellulitis arising in a patient with
      underlying renal cell carcinoma.

PMID- 24945652
TI  - Sclerosing perineurioma: case report and literature review.
AB  - Perineuriomas are rare tumors derived from perineural cells usually presenting as
      a single asymptomatic papule or nodule located on an extremity of an adult. A
      sclerosing subtype has been rarely described. We report a case of painful
      sclerosing perineurioma in a 42-year-old woman.

PMID- 24945653
TI  - Molluscum gladiatorum.
AB  - Molluscum contagiosum is a self-limited disease that presents as small papules
      with central umbilication. Similar to herpes simplex virus type 1 (HSV-1) and
      tinea corporis, participation in wrestling is a risk factor for molluscum
      infection in children and adults. Referred to as herpes gladiatorum, HSV-1 causes
      cutaneous or ocular infections in wrestlers. We propose that molluscum
      contagiosum be referred to as "molluscum gladiatorum" when infection occurs in
      the context of wrestling. We report a case of a high school wrestler who
      presented with molluscum lesions on his neck.

PMID- 24945654
TI  - Intractable prurigo nodularis successfully treated with combination therapy with
      a newly developed excimer laser and topical steroids.
AB  - Prurigo nodularis (PN) is an eruption of lichenified or excoriated nodules
      related to intractable pruritus. A few reports have shown that a 308-nm excimer
      lamp/laser (EL) is effective for intractable PN. Herein, we report on two cases
      of intractable prurigo nodularis successfully treated with a new EL equipped with
      a filter to cut wavelengths shorter than 297 nm. Because this newly developed EL
      yields a therapeutic effect with low cumulative dosages of UV and a lower risk of
      DNA damage, it can be a new treatment option for intractable PN.

PMID- 24945655
TI  - The nuclear progesterone receptor reduces post-sigh apneas during sleep and
      increases the ventilatory response to hypercapnia in adult female mice.
AB  - We tested the hypothesis that the nuclear progesterone receptor (nPR) is involved
      in respiratory control and mediates the respiratory stimulant effect of
      progesterone. Adult female mice carrying a mutation in the nPR gene (PRKO mice)
      and wild-type controls (WT) were implanted with an osmotic pump delivering
      vehicle or progesterone (4 mg/kg/day). The mice were instrumented with EEG and
      neck EMG electrodes connected to a telemetry transmitter. The animals were placed
      in a whole body plethysmograph 7 days after surgery to record ventilation,
      metabolic rate, EEG and neck EMGs for 4 consecutive hours. The animals were
      exposed to hypercapnia (5% CO2), hypoxia (12% O2) and hypoxic-hypercapnia (5%
      CO2+12% O2-5 min each) to assess chemoreflex responses. EEG and EMG signals were
      used to characterize vigilance states (e.g., wake, non-REM, and REM sleep). PRKO
      mice exhibited similar levels of minute ventilation during non-REM and REM sleep,
      and higher frequencies of sighs and post-sigh apneas during non-REM sleep
      compared to WT. Progesterone treatment increased minute ventilation and metabolic
      rate in WT and PRKO mice during non-REM sleep. In WT mice, but not in PRKO mice,
      the ventilation under hypercapnia and hypoxic hypercapnia was enhanced after
      progesterone treatment. We conclude that the nPR reduces apnea frequency during
      non-REM sleep and enhances chemoreflex responses to hypercapnia after
      progesterone treatment. These results also suggest that mechanisms other than nPR
      activation increase metabolic rate in response to progesterone treatment in adult
      female mice. 

PMID- 24945656
TI  - Preclinical detection of variant CJD and BSE prions in blood.
AB  - The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely
      consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE)
      agent. More recently, secondary vCJD cases were identified in patients transfused
      with blood products prepared from apparently healthy donors who later went on to
      develop the disease. As there is no validated assay for detection of vCJD/BSE
      infected individuals the prevalence of the disease in the population remains
      uncertain. In that context, the risk of vCJD blood borne transmission is
      considered as a serious concern by health authorities. In this study, appropriate
      conditions and substrates for highly efficient and specific in vitro
      amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification
      (PMCA) were first identified. This showed that whatever the origin (species) of
      the vCJD/BSE agent, the ovine Q171 PrP substrates provided the best amplification
      performances. These results indicate that the homology of PrP amino-acid sequence
      between the seed and the substrate is not the crucial determinant of the vCJD
      agent propagation in vitro. The ability of this method to detect endogenous
      vCJD/BSE agent in the blood was then defined. In both sheep and primate models of
      the disease, the assay enabled the identification of infected individuals in the
      early preclinical stage of the incubation period. Finally, sample panels that
      included buffy coat from vCJD affected patients and healthy controls were tested
      blind. The assay identified three out of the four tested vCJD affected patients
      and no false positive was observed in 141 healthy controls. The negative results
      observed in one of the tested vCJD cases concurs with results reported by others
      using a different vCJD agent blood detection assay and raises the question of the
      potential absence of prionemia in certain patients. 

PMID- 24945657
TI  - The prognostic significance of cancer-associated fibroblasts in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Cancer-associated fibroblasts (CAF) are activated fibroblasts in the
      cancer stroma and play an important role in cancer progression. Some reports have
      indicated the correlation between the expression of CAF markers and adverse
      prognosis in several cancers. However, no reports have studied CAF phenotype and
      its clinical relevance in esophageal squamous cell carcinoma (ESCC). METHODS: We
      investigated CAF phenotype of ESCC based on histology and immunohistochemical
      expressions of five CAF markers such as fibroblast activation protein (FAP),
      smooth muscle actin (SMA), fibroblast-specific protein-1 (FSP1), platelet-derived
      growth factor receptor (PDGFRalpha), and PDGFRbeta in 116 ESCC tissue samples.
      Besides, we also examined the correlation of the CAF phenotype with clinical
      relevance as well as other cancer-microenvironment related factors. RESULTS:
      Histologically immature CAF phenotype was correlated with poor prognosis
      (p<0.001) and associated with increased microvessel density, increased tumor
      associated macrophages, and epithelial to mesenchymal transition. CAF markers
      were characteristically expressed in stromal fibroblast close to tumor cells and
      the expression pattern of 5 CAF markers was highly heterogeneous in every
      individual cases. Of five CAF markers, SMA, FSP1, and PDGFRalpha were unfavorable
      prognostic indicators of ESCC. The number of positive CAF markers was greater in
      ESCC with immature CAFs than in those with mature ones. CONCLUSIONS: Our results
      demonstrate that histologic classification of CAF phenotype is a reliable and
      significant prognostic predictor in ESCC. CAF markers have the potential to be
      diagnostic and therapeutic targets in ESCC.

PMID- 24945659
TI  - A child sexual abuse research project: a brief endnote.
AB  - There is a dearth of research on sexual abuse perpetrated by educators. Although
      the problem is receiving increasing attention, little emphasis has been placed on
      abuse directed at younger schoolchildren and on offenders' accounts of this form
      of abuse. Here, we attempt to address this gap in knowledge by exploring the
      narratives of five convicted, imprisoned male child sexual abusers, each of whom
      worked with children in educational settings in the United Kingdom. We draw on
      four themes that emerged from detailed interviews with offenders, namely: the
      power of reputation, authority and control, the "front of invulnerability," and
      disclosure of abuse. We conclude by considering the implications of our work for
      policy and practice. 

PMID- 24945658
TI  - Paracellular transport through healthy and cystic fibrosis bronchial epithelial
      cell lines--do we have a proper model?
AB  - It has been reported recently that the cystic fibrosis transmembrane conductance
      regulator (CFTR) besides transcellular chloride transport, also controls the
      paracellular permeability of bronchial epithelium. The aim of this study was to
      test whether overexpressing wtCFTR solely regulates paracellular permeability of
      cell monolayers. To answer this question we used a CFBE41o- cell line transfected
      with wtCFTR or mutant F508del-CFTR and compered them with parental line and
      healthy 16HBE14o- cells. Transepithelial electrical resistance (TER) and
      paracellular fluorescein flux were measured under control and CFTR-stimulating
      conditions. CFTR stimulation significant decreased TER in 16HBE14o- and also in
      CFBE41o- cells transfected with wtCFTR. In contrast, TER increased upon
      stimulation in CFBE41o- cells and CFBE41o- cells transfected with F508del-CFTR.
      Under non-stimulated conditions, all four cell lines had similar paracellular
      fluorescein flux. Stimulation increased only the paracellular permeability of the
      16HBE14o- cell monolayers. We observed that 16HBE14o- cells were significantly
      smaller and showed a different structure of cell-cell contacts than CFBE41o- and
      its overexpressing clones. Consequently, 16HBE14o- cells have about 80% more cell
      cell contacts through which electrical current and solutes can leak. Also tight
      junction protein composition is different in 'healthy' 16HBE14o- cells compared
      to 'cystic fibrosis' CFBE41o- cells. We found that claudin-3 expression was
      considerably stronger in 16HBE14o- cells than in the three CFBE41o- cell clones
      and thus independent of the presence of functional CFTR. Together, CFBE41o- cell
      line transfection with wtCFTR modifies transcellular conductance, but not the
      paracellular permeability. We conclude that CFTR overexpression is not sufficient
      to fully reconstitute transport in CF bronchial epithelium. Hence, it is not
      recommended to use those cell lines to study CFTR-dependent epithelial transport.

PMID- 24945661
TI  - Methodological considerations on tract-based spatial statistics (TBSS).
AB  - Having gained a tremendous amount of popularity since its introduction in 2006,
      tract-based spatial statistics (TBSS) can now be considered as the standard
      approach for voxel-based analysis (VBA) of diffusion tensor imaging (DTI) data.
      Aiming to improve the sensitivity, objectivity, and interpretability of multi
      subject DTI studies, TBSS includes a skeletonization step that alleviates
      residual image misalignment and obviates the need for data smoothing. Although
      TBSS represents an elegant and user-friendly framework that tackles numerous
      concerns existing in conventional VBA methods, it has limitations of its own,
      some of which have already been detailed in recent literature. In this work, we
      present general methodological considerations on TBSS and report on pitfalls that
      have not been described previously. In particular, we have identified specific
      assumptions of TBSS that may not be satisfied under typical conditions. Moreover,
      we demonstrate that the existence of such violations can severely affect the
      reliability of TBSS results. With TBSS being used increasingly, it is of
      paramount importance to acquaint TBSS users with these concerns, such that a well
      informed decision can be made as to whether and how to pursue a TBSS analysis.
      Finally, in addition to raising awareness by providing our new insights, we
      provide constructive suggestions that could improve the validity and increase the
      impact of TBSS drastically. 

PMID- 24945662
TI  - Gambling for self, friends, and antagonists: differential contributions of
      affective and social brain regions on adolescent reward processing.
AB  - Adolescence is a time of increasing emotional arousal, sensation-seeking and risk
      taking, especially in the context of peers. Recent neuroscientific studies have
      pinpointed to the role of the ventral striatum as a brain region which is
      particularly sensitive to reward, and to 'social brain' regions, such as the
      medial prefrontal cortex (mPFC), the precuneus, and the temporal parietal
      junction, as being particularly responsive to social contexts. However, no study
      to date has examined adolescents' sensitivity to reward across different social
      contexts. In this study we examined 249 participants between the ages 8 and 25,
      on a monetary reward-processing task. Participants could win or lose money for
      themselves, their best friend and a disliked peer. Winning for self resulted in a
      mid- to late adolescent specific peak in neural activation in the ventral
      striatum, whereas winning for a disliked peer resulted in a mid- to late
      adolescent specific peak in the mPFC. Our findings reveal that ventral striatum
      and mPFC hypersensitivity in adolescence is dependent on social context. Taken
      together, these results suggest that increased risk-taking and sensation seeking
      observed in adolescence might not be purely related to hyperactivity of the
      ventral striatum, but that these behaviors are probably strongly related to the
      social context in which they occur. 

PMID- 24945660
TI  - Spatial distribution and longitudinal development of deep cortical sulcal
      landmarks in infants.
AB  - Sulcal pits, the locally deepest points in sulci of the highly convoluted and
      variable cerebral cortex, are found to be spatially consistent across human adult
      individuals. It is suggested that sulcal pits are genetically controlled and have
      close relationships with functional areas. To date, the existing imaging studies
      of sulcal pits are mainly focused on adult brains, yet little is known about the
      spatial distribution and temporal development of sulcal pits in the first 2 years
      of life, which is the most dynamic and critical period of postnatal brain
      development. Studying sulcal pits during this period would greatly enrich our
      limited understandings of the origins and developmental trajectories of sulcal
      pits, and would also provide important insights into many neurodevelopmental
      disorders associated with abnormal cortical foldings. In this paper, by using
      surface-based morphometry, for the first time, we systemically investigated the
      spatial distribution and temporal development of sulcal pits in major cortical
      sulci from 73 healthy infants, each with three longitudinal 3T MR scans at term
      birth, 1 year, and 2 years of age. Our results suggest that the spatially
      consistent distributions of sulcal pits in major sulci across individuals have
      already existed at term birth and this spatial distribution pattern keeps
      relatively stable in the first 2 years of life, despite that the cerebral cortex
      expands dramatically and the sulcal depth increases considerably during this
      period. Specially, the depth of sulcal pits increases regionally heterogeneously,
      with more rapid growth in the high-order association cortex, including the
      prefrontal and temporal cortices, than the sensorimotor cortex in the first 2
      years of life. Meanwhile, our results also suggest that there exist hemispheric
      asymmetries of the spatial distributions of sulcal pits in several cortical
      regions, such as the central, superior temporal and postcentral sulci,
      consistently from birth to 2 years of age, which likely has close relationships
      with the lateralization of brain functions of these regions. This study provides
      detailed insights into the spatial distribution and temporal development of deep
      sulcal landmarks in infants.

PMID- 24945663
TI  - Optimal timing of pulse onset for language mapping with navigated repetitive
      transcranial magnetic stimulation.
AB  - OBJECT: Within the primary motor cortex, navigated transcranial magnetic
      stimulation (nTMS) has been shown to yield maps strongly correlated with those
      generated by direct cortical stimulation (DCS). However, the stimulation
      parameters for repetitive nTMS (rTMS)-based language mapping are still being
      refined. For this purpose, the present study compares two rTMS protocols, which
      differ in the timing of pulse train onset relative to picture presentation onset
      during object naming. Results were the correlated with DCS language mapping
      during awake surgery. METHODS: Thirty-two patients with left-sided perisylvian
      tumors were examined by rTMS prior to awake surgery. Twenty patients underwent
      rTMS pulse trains starting at 300 ms after picture presentation onset (delayed
      TMS), whereas another 12 patients received rTMS pulse trains starting at the
      picture presentation onset (ONSET TMS). These rTMS results were then evaluated
      for correlation with intraoperative DCS results as gold standard in terms of
      differential consistencies in receiver operating characteristics (ROC)
      statistics. Logistic regression analysis by protocols and brain regions were
      conducted. RESULTS: Within and around Broca's area, there was no difference in
      sensitivity (onset TMS: 100%, delayed TMS: 100%), negative predictive value (NPV)
      (onset TMS: 100%, delayed TMS: 100%), and positive predictive value (PPV) (onset
      TMS: 55%, delayed TMS: 54%) between the two protocols compared to DCS. However,
      specificity differed significantly (onset TMS: 67%, delayed TMS: 28%). In
      contrast, for posterior language regions, such as supramarginal gyrus, angular
      gyrus, and posterior superior temporal gyrus, early pulse train onset stimulation
      showed greater specificity (onset TMS: 92%, delayed TMS: 20%), NPV (onset TMS:
      92%, delayed TMS: 57%) and PPV (onset TMS: 75%, delayed TMS: 30%) with comparable
      sensitivity (onset TMS: 75%, delayed TMS: 70%). Logistic regression analysis also
      confirmed the greater fit of the predictions by rTMS that had the pulse train
      onset coincident with the picture presentation onset when compared to the delayed
      stimulation. Analyses of differential disruption patterns of mapped cortical
      regions were further able to distinguish clusters of cortical regions standardly
      associated with semantic and pre-vocalization phonological networks proposed in
      various models of word production. Repetitive nTMS predictions by both protocols
      correlate well with DCS outcomes especially in Broca's region, particularly with
      regard to TMS negative predictions. CONCLUSIONS: With this study, we have
      demonstrated that rTMS stimulation onset coincident with picture presentation
      onset improves the accuracy of preoperative language maps, particularly within
      posterior language areas. Moreover, immediate and delayed pulse train onsets may
      have complementary disruption patterns that could differentially capture cortical
      regions causally necessary for semantic and pre-vocalization phonological
      networks.

PMID- 24945664
TI  - Stereoscopic depth increases intersubject correlations of brain networks.
AB  - Three-dimensional movies presented via stereoscopic displays have become more
      popular in recent years aiming at a more engaging viewing experience. However,
      neurocognitive processes associated with the perception of stereoscopic depth in
      complex and dynamic visual stimuli remain understudied. Here, we investigate the
      influence of stereoscopic depth on both neurophysiology and subjective
      experience. Using multivariate statistical learning methods, we compare the brain
      activity of subjects when freely watching the same movies in 2D and in 3D.
      Subjective reports indicate that 3D movies are more strongly experienced than 2D
      movies. On the neural level, we observe significantly higher intersubject
      correlations of cortical networks when subjects are watching 3D movies relative
      to the same movies in 2D. We demonstrate that increases in intersubject
      correlations of brain networks can serve as neurophysiological marker for
      stereoscopic depth and for the strength of the viewing experience. 

PMID- 24945666
TI  - Uncovering cortical MEG responses to listened audiobook stories.
AB  - Naturalistic stimuli, such as normal speech and narratives, are opening up
      intriguing prospects in neuroscience, especially when merging neuroimaging with
      machine learning methodology. Here we propose a task-optimized spatial filtering
      strategy for uncovering individual magnetoencephalographic (MEG) responses to
      audiobook stories. Ten subjects listened to 1-h-long recording once, as well as
      to 48 repetitions of a 1-min-long speech passage. Employing response
      replicability as statistical validity and utilizing unsupervised learning
      methods, we trained spatial filters that were able to generalize over datasets of
      an individual. For this blind-signal-separation (BSS) task, we derived a version
      of multi-set similarity-constrained canonical correlation analysis (SimCCA) that
      theoretically provides maximal signal-to-noise ratio (SNR) in this setting.
      Irrespective of significant noise in unaveraged MEG traces, the method
      successfully uncovered feasible time courses up to ~120 Hz, with the most
      prominent signals below 20 Hz. Individual trial-to-trial correlations of such
      time courses reached the level of 0.55 (median 0.33 in the group) at ~0.5 Hz,
      with considerable variation between subjects. By this filtering, the SNR
      increased up to 20 times. In comparison, independent component analysis (ICA) or
      principal component analysis (PCA) did not improve SNR notably. The validity of
      the extracted brain signals was further assessed by inspecting their associations
      with the stimulus, as well as by mapping the contributing cortical signal
      sources. The results indicate that the proposed methodology effectively reduces
      noise in MEG recordings to that extent that brain responses can be seen to
      nonrecurring audiobook stories. The study paves the way for applications aiming
      at accurately modeling the stimulus-response-relationship by tackling the
      response variability, as well as for real-time monitoring of brain signals of
      individuals in naturalistic experimental conditions.

PMID- 24945665
TI  - Dissociable causal roles for left and right parietal cortex in controlling
      attentional biases from the contents of working memory.
AB  - The contents of working memory (WM) steer visual attention, but the extent of
      this guidance can be strategically enhanced or inhibited when WM content is
      reliably helpful or harmful to a visual task. Current understanding of the neural
      substrates mediating the cognitive control over WM biases is limited, however, by
      the correlational nature of functional MRI approaches. A recent fMRI study
      provided suggestive evidence for a functional lateralization of these control
      processes in posterior parietal cortex (PPC): activity in left PPC correlated
      with the presentation of WM cues that ought to be strategically enhanced to
      optimize performance, while activity in the right PPC correlated with the
      presentation of cues that ought to be inhibited to prevent detrimental
      attentional biases in a visual search. Here, we aimed to directly assess whether
      the left and right PPC are causally involved in the cognitive control of WM
      biases, and to clarify their precise functional contributions. We therefore
      applied 1 Hz repetitive transcranial magnetic stimulation (rTMS) to left and
      right PPC (and a vertex control site) prior to administering a behavioral task
      assessing WM biasing control functions. We observed that the perturbation of left
      PPC eliminated the strategic benefit of predictably helpful WM cueing, while the
      perturbation of right PPC amplified the cost of unpredictable detrimental WM
      cueing. The left and right PPC thus play distinct causal roles in WM-attention
      interactions: the left PPC to maximize benefits, and the right PPC to minimize
      costs, of internally maintained content on visual attention.

PMID- 24945669
TI  - A copula approach to assessing Granger causality.
AB  - In neuroscience, as in many other fields of science and engineering, it is
      crucial to assess the causal interactions among multivariate time series. Granger
      causality has been increasingly used to identify causal influence between time
      series based on multivariate autoregressive models. Such an approach is based on
      linear regression framework with implicit Gaussian assumption of model noise
      residuals having constant variance. As a consequence, this measure cannot detect
      the cause-effect relationship in high-order moments and nonlinear causality.
      Here, we propose an effective model-free, copula-based Granger causality measure
      that can be used to reveal nonlinear and high-order moment causality. We first
      formulate Granger causality as the log-likelihood ratio in terms of conditional
      distribution, and then derive an efficient estimation procedure using conditional
      copula. We use resampling techniques to build a baseline null-hypothesis
      distribution from which statistical significance can be derived. We perform a
      series of simulations to investigate the performance of our copula-based Granger
      causality, and compare its performance against other state-of-the-art techniques.
      Our method is finally applied to neural field potential time series recorded from
      visual cortex of a monkey while performing a visual illusion task. 

PMID- 24945668
TI  - Meta-analytic connectivity modeling revisited: controlling for activation base
      rates.
AB  - Co-activation of distinct brain regions is a measure of functional interaction,
      or connectivity, between those regions. The co-activation pattern of a given
      region can be investigated using seed-based activation likelihood estimation meta
      analysis of functional neuroimaging data stored in databases such as BrainMap.
      This method reveals inter-regional functional connectivity by determining brain
      regions that are consistently co-activated with a given region of interest (the
      "seed") across a broad range of experiments. In current implementations of this
      meta-analytic connectivity modeling (MACM), significant spatial convergence (i.e.
      consistent co-activation) is distinguished from noise by comparing it against an
      unbiased null-distribution of random spatial associations between experiments
      according to which all gray-matter voxels have the same chance of convergence. As
      the a priori probability of finding activation in different voxels markedly
      differs across the brain, computing such a quasi-rectangular null-distribution
      renders the detection of significant convergence more likely in those voxels that
      are frequently activated. Here, we propose and test a modified MACM approach that
      takes this activation frequency bias into account. In this new specific co
      activation likelihood estimation (SCALE) algorithm, a null-distribution is
      generated that reflects the base rate of reporting activation in any given voxel
      and thus equalizes the a priori chance of finding across-study convergence in
      each voxel of the brain. Using four exemplary seed regions (right visual area V4,
      left anterior insula, right intraparietal sulcus, and subgenual cingulum), our
      tests corroborated the enhanced specificity of the modified algorithm, indicating
      that SCALE may be especially useful for delineating distinct core networks of co
      activation. 

PMID- 24945670
TI  - Conscious auditory perception related to long-range synchrony of gamma
      oscillations.
AB  - While the role of synchronized oscillatory activity in the gamma-band frequency
      range for conscious perception is well established in the visual domain, there is
      limited evidence concerning neurophysiological mechanisms in conscious auditory
      perception. In the current study, we addressed this issue with 64-channel EEG and
      a dichotic listening (DL) task in twenty-five healthy participants. The typical
      finding of DL is a more frequent conscious perception of the speech syllable
      presented to the right ear (RE), which is attributed to the supremacy of the
      contralateral pathways running from the RE to the speech-dominant left
      hemisphere. In contrast, the left ear (LE) input initially accesses the right
      hemisphere and needs additional transfer via interhemispheric pathways before it
      is processed in the left hemisphere. Using lagged phase synchronization (LPS)
      analysis and eLORETA source estimation we examined the functional connectivity
      between right and left primary and secondary auditory cortices in the main
      frequency bands (delta, theta, alpha, beta, gamma) during RE/LE-reports.
      Interhemispheric LPS between right and left primary and secondary auditory
      cortices was specifically increased in the gamma-band range, when participants
      consciously perceived the syllable presented to the LE. Our results suggest that
      synchronous gamma oscillations are involved in interhemispheric transfer of
      auditory information. 

PMID- 24945667
TI  - Distinct MEG correlates of conscious experience, perceptual reversals and
      stabilization during binocular rivalry.
AB  - During binocular rivalry, visual perception alternates spontaneously between two
      different monocular images. Such perceptual reversals are slowed or halted if
      stimuli are presented intermittently with inter-stimulus intervals larger than
      ~400 ms--a phenomenon called stabilization. Often, the neural correlates of
      reversal and stabilization are studied separately, and both phenomena in turn are
      studied separately from the neural correlates of conscious perception. To
      distinguish the neural correlates of perceptual content, stabilization and
      reversal, we recorded MEG signals associated with each in the same group of
      healthy humans observing repeated trials of intermittent presentation of a
      dichoptic stimulus. Perceptual content correlated mainly with modulation of
      stimulus-specific activity in occipital/temporal areas 150-270 ms after stimulus
      onset, possibly reflecting inhibition of the neural populations representing the
      suppressed image. Stability of perception reflected a gradual build-up of this
      modulation across at least 10 trials and was also, to some extent, associated
      with parietal activity 40-90 ms and 220-270 ms after stimulus onset. Perceptual
      reversals, in contrast, were associated with parietal (150-270 ms) and temporal
      (150-210 ms) activity on the trial before the reversal and a gradual change in
      perception-specific activity in occipital (150-270 ms) and temporal (220-420 ms)
      areas across at least 10 trials leading up to a reversal. Mechanistically, these
      findings suggest that stability of perception during rivalry is maintained by
      modulation of activity related to the two monocular images, and gradual
      adaptation of neuronal populations leads to instability that is eventually
      resolved by signals from parietal and late sensory cortices.

PMID- 24945672
TI  - Functional quantitative susceptibility mapping (fQSM).
AB  - Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging
      (fMRI) is a powerful technique, typically based on the statistical analysis of
      the magnitude component of the complex time-series. Here, we additionally
      interrogated the phase data of the fMRI time-series and used quantitative
      susceptibility mapping (QSM) in order to investigate the potential of functional
      QSM (fQSM) relative to standard magnitude BOLD fMRI. High spatial resolution data
      (1mm isotropic) were acquired every 3 seconds using zoomed multi-slice gradient
      echo EPI collected at 7 T in single orientation (SO) and multiple orientation
      (MO) experiments, the latter involving 4 repetitions with the subject's head
      rotated relative to B0. Statistical parametric maps (SPM) were reconstructed for
      magnitude, phase and QSM time-series and each was subjected to detailed analysis.
      Several fQSM pipelines were evaluated and compared based on the relative number
      of voxels that were coincidentally found to be significant in QSM and magnitude
      SPMs (common voxels). We found that sensitivity and spatial reliability of fQSM
      relative to the magnitude data depended strongly on the arbitrary significance
      threshold defining "activated" voxels in SPMs, and on the efficiency of spatio
      temporal filtering of the phase time-series. Sensitivity and spatial reliability
      depended slightly on whether MO or SO fQSM was performed and on the QSM
      calculation approach used for SO data. Our results present the potential of fQSM
      as a quantitative method of mapping BOLD changes. We also critically discuss the
      technical challenges and issues linked to this intriguing new technique.

PMID- 24945671
TI  - Sub-millimeter imaging of brain-free water for rapid volume assessment in
      atrophic brains.
AB  - INTRODUCTION: Cerebral atrophy occurs in healthy aging, and in disease processes
      such as multiple sclerosis (MS), it correlates with disability accumulation.
      Imaging measurements of brain atrophy are commonly based on tissue segmentation,
      which is susceptible to classification errors and inconsistencies. High
      resolution imaging techniques with strong contrast between brain parenchyma and
      cerebrospinal fluid (CSF) might allow fully automated, rapid, threshold-based
      determination of the free water in the brain. We hypothesized that total brain
      free-water (BFW) volume and BFW volume expressed as a normalized fraction of the
      intracranial volume ("BFW fraction"), determined from heavily T2-weighted images,
      would be useful surrogates for cerebral atrophy and therefore would correlate
      with clinical measures of disability in MS. METHODS: Whole brains of 83 MS cases
      and 7 healthy volunteers were imaged with a 4.7-min, heavily T2-weighted sequence
      on a 3T MRI scanner, acquiring 650-MUm isotropic voxels. MS cases were clinically
      assessed on the Expanded Disability Status Scale (EDSS), Scripps Neurological
      Rating Scale (SNRS), Paced Auditory Serial Addition Test (PASAT), 9-Hole Peg Test
      (9HPT), Symbol Digit Modalities Test (SDMT), and 25-Foot Timed Walk. Twelve of
      the MS cases were rescanned within an average of 1.8 months to assess
      reproducibility. Automated calculations of BFW volume and BFW fraction were
      correlated with clinical measures of disability upon adjusting for age and sex.
      Results were compared to data from T1-based approaches (SIENAX and Lesion-TOADS).
      RESULTS AND DISCUSSION: BFW volume was automatically derived from heavily T2
      weighted images with no need for separate skull stripping. BFW volume and
      fraction had mean scan-rescan coefficients of variation of 1.5% and 1.9%,
      respectively, similar to the T1-based approaches tested here. BFW fraction more
      strongly correlated with clinical measures than T1-derived results. Among those
      clinical measures, modality-specific disability scores, such as SDMT and 9HPT,
      were more strongly associated with BFW fraction than composite measures, such as
      EDSS and SNRS. CONCLUSION: The BFW method robustly estimates cerebral atrophy in
      an automated, fast, and reliable manner, and as such may prove a useful addition
      to imaging protocols for clinical practice and trials.

PMID- 24945673
TI  - Mismatch negativity to acoustical illusion of beat: how and where the change
      detection takes place?
AB  - In case of binaural presentation of two tones with slightly different frequencies
      the structures of brainstem can no longer follow the interaural time differences
      (ITD) resulting in an illusionary perception of beat corresponding to frequency
      difference between the two prime tones. Hence, the beat-frequency does not exist
      in the prime tones presented to either ear. This study used binaural beats to
      explore the nature of acoustic deviance detection in humans by means of
      magnetoencephalography (MEG). Recent research suggests that the auditory change
      detection is a multistage process. To test this, we employed 26 Hz-binaural beats
      in a classical oddball paradigm. However, the prime tones (250 Hz and 276 Hz)
      were switched between the ears in the case of the deviant-beat. Consequently,
      when the deviant is presented, the cochleae and auditory nerves receive a "new
      afferent", although the standards and the deviants are heard identical (26 Hz
      beats). This allowed us to explore the contribution of auditory periphery to
      change detection process, and furthermore, to evaluate its influence on beats
      related auditory steady-state responses (ASSRs). LORETA-source current density
      estimates of the evoked fields in a typical mismatch negativity time-window (MMN)
      and the subsequent difference-ASSRs were determined and compared. The results
      revealed an MMN generated by a complex neural network including the right
      parietal lobe and the left middle frontal gyrus. Furthermore, difference-ASSR was
      generated in the paracentral gyrus. Additionally, psychophysical measures showed
      no perceptual difference between the standard- and deviant-beats when isolated by
      noise. These results suggest that the auditory periphery has an important
      contribution to novelty detection already at sub-cortical level. Overall, the
      present findings support the notion of hierarchically organized acoustic novelty
      detection system.

PMID- 24945675
TI  - Ultra-Broadband Dielectric and Optical Kerr-Effect Study of the Ionic Liquids
      Ethyl and Propylammonium Nitrate.
AB  - Dielectric relaxation (DR) and optical Kerr-effect (OKE) spectra of the
      archetypal protic ionic liquids ethyl- and propylammonium nitrate (EAN and PAN)
      have been measured over an unusually large frequency range from 200 MHz to 10 THz
      at temperatures (mostly) between 5 and 65  degrees C. Analysis of the low
      frequency alpha-relaxation, associated with the cooperative relaxations of the
      cations (DR) and anions (OKE) and any clusters present, indicated that ion
      reorientation in EAN is decoupled from viscosity and occurs via cooperative
      relaxation involving large-angle jumps rather than rotational diffusion. Detailed
      consideration of the high-frequency parts of the DR and OKE spectra showed that
      the observed intensities were a complex combination of overlapping and possibly
      coupled modes. In addition to previously identified intermolecular H-bond
      vibrations, there are significant contributions from the librations of the
      cations and anions. The present assignments were shown to be consistent with the
      isotopic shifts observed for deuterated EAN. 

PMID- 24945674
TI  - Genetic variants of EGF and VEGF predict prognosis of patients with advanced
      esophageal squamous cell carcinoma.
AB  - PURPOSE: To investigate the association between genetic polymorphisms of growth
      factor-related genes and prognosis in patients with advanced esophageal squamous
      cell carcinoma (ESCC). PATIENTS AND METHODS: A total of 334 ESCC patients with
      advanced tumor stages (stages IIB, III and IV) were enrolled in the study. The
      genotypes of 14 candidate single nucleotide polymorphisms (SNPs) involved in
      growth factor-related functions were analyzed using iPLEX Gold technology from
      the genomic DNA of peripheral leukocytes, and were correlated with the clinical
      outcome of patients. Serum levels of growth factors were examined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: The genetic polymorphisms of
      EGF:rs4444903, EGF:rs2237051 and VEGF:rs2010963 showed significant associations
      with overall survival (OS) of advanced ESCC patients (A/A+ A/G vs. GG, [HR =
      0.77, 95% CI = 0.60-0.99, P = 0.039 for rs4444903; A/G+ G/G vs. A/A, [HR = 0.74,
      95% CI = 0.58-0.95, P = 0.019 for rs2237051; G/G+G/C vs. C/C, [HR] inves = 0.69,
      95% CI = 0.50-0.95, P = 0.023 for rs2010963). EGFR:rs2227983 and 3 SNPs of PIK3CA
      also showed borderline significant correlation with OS of advanced ESCC patients
      (P = 0.058 for rs2227983; P = 0.069, 0.091 and 0.067 for rs6443624, rs7651265 and
      rs7621329 of PIK3CA respectively). According to cumulative effect analysis of
      multiple SNPs, patients carrying 4 unfavorable genotypes exhibited more than a 3
      fold increased risk of mortality. Finally, both EGF and VEGF expression levels
      significantly associated with patient mortality. CONCLUSION: The genetic variants
      and expression levels of EGF and VEGF can serve as prognostic predictors in
      patients with advanced ESCC, and thus provide more information for optimizing
      personalized therapies for patients with ESCC.

PMID- 24945676
TI  - Detecting falls with wearable sensors using machine learning techniques.
AB  - Falls are a serious public health problem and possibly life threatening for
      people in fall risk groups. We develop an automated fall detection system with
      wearable motion sensor units fitted to the subjects' body at six different
      positions. Each unit comprises three tri-axial devices (accelerometer, gyroscope,
      and magnetometer/compass). Fourteen volunteers perform a standardized set of
      movements including 20 voluntary falls and 16 activities of daily living (ADLs),
      resulting in a large dataset with 2520 trials. To reduce the computational
      complexity of training and testing the classifiers, we focus on the raw data for
      each sensor in a 4 s time window around the point of peak total acceleration of
      the waist sensor, and then perform feature extraction and reduction. Most earlier
      studies on fall detection employ rule-based approaches that rely on simple
      thresholding of the sensor outputs. We successfully distinguish falls from ADLs
      using six machine learning techniques (classifiers): the k-nearest neighbor (k
      NN) classifier, least squares method (LSM), support vector machines (SVM),
      Bayesian decision making (BDM), dynamic time warping (DTW), and artificial neural
      networks (ANNs). We compare the performance and the computational complexity of
      the classifiers and achieve the best results with the k-NN classifier and LSM,
      with sensitivity, specificity, and accuracy all above 99%. These classifiers also
      have acceptable computational requirements for training and testing. Our approach
      would be applicable in real-world scenarios where data records of indeterminate
      length, containing multiple activities in sequence, are recorded. 

PMID- 24945677
TI  - Application of an electronic nose instrument to fast classification of Polish
      honey types.
AB  - The paper presents practical utilization of an electronic nose prototype, based
      on the FIGARO semiconductor sensors, in fast classification of Polish honey types
      acacia flower, linden flower, rape, buckwheat and honeydew ones. A set of
      thermostating modules of the prototype provided gradient temperature
      characteristics of barbotage-prepared gas mixtures and stable measurement
      conditions. Three chemometric data analysis methods were employed for the honey
      samples classification: principal component analysis (PCA), linear discriminant
      analysis (LDA) and cluster analysis (CA) with the furthest neighbour method. The
      investigation confirmed usefulness of this type of instrument in correct
      classification of all aforementioned honey types. In order to provide optimum
      measurement conditions during honey samples classification the following
      parameters were selected: volumetric flow rate of carrier gas-15 L/h, barbotage
      temperature-35  degrees C, time of sensor signal acquisition since barbotage
      process onset-60 s. Chemometric analysis allowed discrimination of three honey
      types using PCA and CA and all five honey types with LDA. The reproducibility of
      96% of the results was within the range 4.9%-8.6% CV. 

PMID- 24945678
TI  - A ubiquitous sensor network platform for integrating smart devices into the
      semantic sensor web.
AB  - Ongoing Sensor Web developments make a growing amount of heterogeneous sensor
      data available to smart devices. This is generating an increasing demand for
      homogeneous mechanisms to access, publish and share real-world information. This
      paper discusses, first, an architectural solution based on Next Generation
      Networks: a pilot Telco Ubiquitous Sensor Network (USN) Platform that embeds
      several OGC(r) Sensor Web services. This platform has already been deployed in
      large scale projects. Second, the USN-Platform is extended to explore a first
      approach to Semantic Sensor Web principles and technologies, so that smart
      devices can access Sensor Web data, allowing them also to share richer
      (semantically interpreted) information. An experimental scenario is presented: a
      smart car that consumes and produces real-world information which is integrated
      into the Semantic Sensor Web through a Telco USN-Platform. Performance tests
      revealed that observation publishing times with our experimental system were well
      within limits compatible with the adequate operation of smart safety assistance
      systems in vehicles. On the other hand, response times for complex queries on
      large repositories may be inappropriate for rapid reaction needs. 

PMID- 24945679
TI  - Obstacle classification and 3D measurement in unstructured environments based on
      ToF cameras.
AB  - Inspired by the human 3D visual perception system, we present an obstacle
      detection and classification method based on the use of Time-of-Flight (ToF)
      cameras for robotic navigation in unstructured environments. The ToF camera
      provides 3D sensing by capturing an image along with per-pixel 3D space
      information. Based on this valuable feature and human knowledge of navigation,
      the proposed method first removes irrelevant regions which do not affect robot's
      movement from the scene. In the second step, regions of interest are detected and
      clustered as possible obstacles using both 3D information and intensity image
      obtained by the ToF camera. Consequently, a multiple relevance vector machine
      (RVM) classifier is designed to classify obstacles into four possible classes
      based on the terrain traversability and geometrical features of the obstacles.
      Finally, experimental results in various unstructured environments are presented
      to verify the robustness and performance of the proposed approach. We have found
      that, compared with the existing obstacle recognition methods, the new approach
      is more accurate and efficient. 

PMID- 24945680
TI  - Composition and dynamics of the Black Sea benthopelagic plankton and its
      contribution to the near-shore plankton communities.
AB  - At a shallow (7 m) near-shore sampling site in the Black Sea we analyzed
      composition, abundance, and biomass of benthopelagic organisms and the
      contribution these animals make to the total plankton. The site was monitored
      across several years (1996-2001; 2006-2007) whilst for 1999-2000 the seasonal
      variations were analysed. A total of 321 samples from Golubaja Bay near
      Novorossiysk (44 degrees 34'31.04" N, 37 degrees 58'45.11" E) in 1996-2007 were
      taken with a Judey net. The benthopelagic fauna was represented by 69 taxa, a
      diversity comparable to similar shelf areas. The benthopelagic component played
      an important role in near-shore plankton communities in the Black Sea accounting
      for 50% of the total zooplankton biomass at night during all seasons. Abundance
      and biomass of the benthopelagic animals showed seasonal fluctuations, the
      highest biomass being recorded during winter (>75% of the total zooplankton
      biomass) and early spring due to large amphipods, whilst the highest abundances
      occur during late summer because of numerous young stages of various taxa.
      Amphipods, mysids, and decapods are the main contributors to the plankton biomass
      and abundances. Both night and daytime samples are strongly recommended for the
      adequate description of the near-shore plankton communities. 

PMID- 24945681
TI  - Evaluation of the World Health Organization 2010 grading system in surgical
      outcome and prognosis of pancreatic neuroendocrine tumors.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical consistency
      of the new World Health Organization 2010 grading and the European Neuroendocrine
      Tumor Society 2006 TNM staging systems on the surgical outcome for patients with
      pancreatic neuroendocrine tumors (p-NETs). Moreover, we will discuss their
      prognostic value. METHODS: The medical records of 110 consecutive patients with p
      NETs who were surgically treated in our center from January 2002 to December 2012
      were reviewed. RESULTS: Sixty-five patients were diagnosed as having
      neuroendocrine tumor G1, 27 patients had neuroendocrine tumor G2, 14 patients had
      neuroendocrine carcinoma G3, and 4 patients had mixed adenoneuro endocrine
      carcinoma; the survival rates at 5 years were 82.6%, 52.7%, 25.7%, and 0%,
      respectively (P < 0.001). The TNM stage was I in 48 patients, II in 39 patients,
      III in 11 patients, and IV in 12 patients; the 5-year survival rates were 83.1%,
      72.1%, 0%, and 0%, respectively (P < 0.001). The patients who underwent R0
      resection gained a statistically longer survival time than those who did not (P <
      0.001). CONCLUSIONS: Both classifications accurately reflect the clinical outcome
      of p-NETs. Surgical margin, the World Health Organization 2010 grading, and the
      TNM staging systems may all be meaningful prognostic factors impacting the long
      term survival of patients with p-NETs.

PMID- 24945684
TI  - A diffusion model analysis of developmental changes in children's task switching.
AB  - This study aimed to investigate the underlying processes of the development of
      cognitive flexibility between childhood and young adulthood. We performed a
      diffusion model analysis on the reaction time and accuracy data from four age
      groups (7-, 11-, 15-, and 21-year-olds), who performed a task-switching task. We
      decomposed the data into processes related to the reconfiguration of the
      cognitive system to a new goal (i.e., task-set reconfiguration) and processes
      related to the interference of the previous task (i.e., task-set inertia). The
      developmental patterns of both processes indicated a relatively early maturing
      mechanism, associated with task-set inertia, and a later maturing mechanism,
      relating to task-set reconfiguration. This pattern of results was interpreted in
      terms of the development of the neural mechanisms involved in task switching,
      that is, the (pre-)supplementary motor area and the ventrolateral prefrontal
      cortex. 

PMID- 24945685
TI  - Selective effects of explanation on learning during early childhood.
AB  - Two studies examined the specificity of effects of explanation on learning by
      prompting 3- to 6-year-old children to explain a mechanical toy and comparing
      what they learned about the toy's causal and non-causal properties with children
      who only observed the toy, both with and without accompanying verbalization. In
      Study 1, children were experimentally assigned to either explain or observe the
      mechanical toy. In Study 2, children were classified according to whether the
      content of their response to an undirected prompt involved explanation. Dependent
      measures included whether children understood the toy's functional-mechanical
      relationships, remembered perceptual features of the toy, effectively
      reconstructed the toy, and (for Study 2) generalized the function of the toy when
      constructing a new one. Results demonstrate that across age groups, explanation
      promotes causal learning and generalization but does not improve (and in younger
      children can even impair) memory for causally irrelevant perceptual details. 

PMID- 24945683
TI  - A comparison of clinical, magnetic resonance imaging and pathological findings in
      dogs with gliomatosis cerebri, focusing on cases with minimal magnetic resonance
      imaging changes(?).
AB  - The primary study objective was to determine whether clinical examination and
      magnetic resonance imaging (MRI) can underestimate canine gliomatosis cerebri
      (GC); we also investigated immunohistochemical features. Seven dogs with GC were
      studied; four recruited specifically because of minimal MRI changes.
      Neuroanatomic localization and the distribution of MRI, gross and sub-gross
      lesions were compared with the actual histological distribution of neoplastic
      cells. In six cases, clinical examination predicted focal disease and MRI
      demonstrated a single lesion or appeared normal. Neoplastic cells infiltrated
      many regions deemed normal by clinical examination and MRI, and were Olig2
      positive and glial fibrillary acid protein-negative. Four dogs had concurrent
      gliomas. GC is a differential diagnosis for dogs with focal neurological deficits
      and a normal MRI or a focal MRI lesion. Canine GC is probably mainly
      oligodendrocytic. Type II GC, a solid glioma accompanying diffuse central nervous
      system neoplastic infiltration, occurs in dogs as in people. 

PMID- 24945686
TI  - Early metacognitive abilities: the interplay of monitoring and control processes
      in 5- to 7-year-old children.
AB  - The goal of the current investigation was to compare two monitoring processes
      (judgments of learning [JOLs] and confidence judgments [CJs]) and their
      corresponding control processes (allocation of study time and selection of
      answers to maximize accuracy, respectively) in 5-, 6-, and 7-year-old children
      (N=101). Children learned the meanings of Japanese characters and provided JOLs
      after a study phase and CJs after a memory test. They were given the opportunity
      to control their learning in self-paced study phases and to control their
      accuracy by placing correct answers in a treasure chest and placing incorrect
      answers in a trash can. All three age groups gave significantly higher CJs for
      correct answers compared with incorrect answers, with no age-related differences
      in the magnitude of this difference, suggesting robust metacognitive monitoring
      skills in children as young as 5 years. Furthermore, a link between JOLs and
      study time was found in 6- and 7-year-olds, such that children spent more time
      studying items with low JOLs compared with items with high JOLs. In addition, 6-
      and 7-year-olds, but not 5-year-olds, spent more time studying difficult items
      compared with easier items. Moreover, age-related improvements were found in
      children's use of CJs to guide their selection of answers; although children as
      young as 5 years placed their most confident answers in the treasure chest and
      placed their least confident answers in the trash can, this pattern was more
      robust in older children. Overall, results support the view that some
      metacognitive judgments may be acted on with greater ease than others among young
      children.

PMID- 24945687
TI  - Transfer of figural face aftereffects suggests mature orientation selectivity in
      8-year-olds' face coding.
AB  - Adult face perception mechanisms are tuned to upright faces, and this orientation
      selectivity is central to adult expertise with upright faces. Children are less
      expert than adults, and it has been argued that their face mechanisms are less
      orientation selective than those of adults. Here we used face aftereffects to
      test this hypothesis by examining whether children's aftereffects show greater
      transfer across changes in orientation than do adults' aftereffects. We adapted 7
      to 8-year-old children and adults to figural face distortions in both upright
      and inverted orientations and examined the size of resulting aftereffects in both
      upright and inverted test faces. If children's face mechanisms are less
      orientation selective than those of adults, then children's aftereffects should
      transfer more strongly across changes in orientation. We found no evidence to
      support this prediction. Children's and adults' aftereffects were similarly
      reduced by orientation differences between adapt and test. These results indicate
      that children, like adults, show a high degree of orientation selectivity in face
      shape coding and suggest that neural tuning to face orientation may be mature by
      8 years of age. Our findings are consistent with an emerging view that many of
      the key attributes of specialized face perception emerge much earlier in
      development than previously thought.

PMID- 24945688
TI  - The moderating effect of orthographic consistency on oral vocabulary learning in
      monolingual and bilingual children.
AB  - Two studies were conducted to assess whether (a) the incidental presence of print
      facilitates the acquisition of oral vocabulary, (b) the facilitative effect of
      print is moderated by phoneme-to-grapheme consistency, and (c) the findings
      obtained with monolingual children generalize to bilingual children. In total, 71
      monolingual French-speaking children (M age = 9 years 2 months) in Study 1 and 64
      bilingual children (M age = 9 years 3 months) in Study 2 participated in one of
      three conditions: consistent print, inconsistent print, or no print. Children
      were to learn novel labels for unfamiliar objects in a paired-associate paradigm.
      In both studies, print facilitated the acquisition and recall of expressive
      vocabulary. The effect of print consistency, however, varied across studies. As
      expected, monolingual children exposed to consistent print learned more novel
      labels than children exposed to inconsistent print. In contrast, bilingual
      children exposed to inconsistent print learned and recalled more labels than
      children exposed to consistent print. These intriguing findings might be due to
      differences in attention allocation during training.

PMID- 24945689
TI  - The first endogenous herpesvirus, identified in the tarsier genome, and novel
      sequences from primate rhadinoviruses and lymphocryptoviruses.
AB  - Herpesviridae is a diverse family of large and complex pathogens whose genomes
      are extremely difficult to sequence. This is particularly true for clinical
      samples, and if the virus, host, or both genomes are being sequenced for the
      first time. Although herpesviruses are known to occasionally integrate in host
      genomes, and can also be inherited in a Mendelian fashion, they are notably
      absent from the genomic fossil record comprised of endogenous viral elements
      (EVEs). Here, we combine paleovirological and metagenomic approaches to both
      explore the constituent viral diversity of mammalian genomes and search for
      endogenous herpesviruses. We describe the first endogenous herpesvirus from the
      genome of the Philippine tarsier, belonging to the Roseolovirus genus, and
      characterize its highly defective genome that is integrated and flanked by
      unambiguous host DNA. From a draft assembly of the aye-aye genome, we use
      bioinformatic tools to reveal over 100,000 bp of a novel rhadinovirus that is the
      first lemur gammaherpesvirus, closely related to Kaposi's sarcoma-associated
      virus. We also identify 58 genes of Pan paniscus lymphocryptovirus 1, the bonobo
      equivalent of human Epstein-Barr virus. For each of the viruses, we postulate
      gene function via comparative analysis to known viral relatives. Most notably,
      the evidence from gene content and phylogenetics suggests that the aye-aye
      sequences represent the most basal known rhadinovirus, and indicates that
      tumorigenic herpesviruses have been infecting primates since their emergence in
      the late Cretaceous. Overall, these data show that a genomic fossil record of
      herpesviruses exists despite their extremely large genomes, and expands the known
      diversity of Herpesviridae, which will aid the characterization of pathogenesis.
      Our analytical approach illustrates the benefit of intersecting evolutionary
      approaches with metagenomics, genetics and paleovirology. 

PMID- 24945691
TI  - Bidirectional association between mental health and physical activity in older
      adults: Whitehall II prospective cohort study.
AB  - OBJECTIVE: To investigate longitudinal and bidirectional associations between
      mental health and physical activity from midlife into old age. METHODS: Analysis
      was based on data from 6909 participants (aged 45 to 69 in 1997/99) from the
      Whitehall II cohort in the UK. Latent growth curve analysis examined possible
      bidirectional associations between the SF-36 Mental Component Summary and weekly
      physical activity measured at three time-points over ten years. RESULTS: Mental
      health and physical activity were associated at baseline (beta=0.17, 95% CI 0.13,
      0.21) and associations persisted into old age. In the latent growth curve model,
      both mental health and physical activity increased and their rates of change
      'moved together' over time (beta=0.24, 95% CI 0.11, 0.37). Relatively high
      baseline levels of either variable were associated with slightly slower increases
      in the other outcome (beta=-0.02, 95% CI -0.03, -0.01; beta=-0.07, 95% CI -0.11, 
      0.13), which are thought to reflect regression to the mean. However, those who
      started high on either variable remained the most advantaged at end of follow-up.
      CONCLUSIONS: From midlife to old age, greater physical activity is associated
      with better mental health and vice versa. These findings suggest persistent
      longitudinal and bidirectional associations between physical activity and mental
      health.

PMID- 24945690
TI  - A novel peptidoglycan binding protein crucial for PBP1A-mediated cell wall
      biogenesis in Vibrio cholerae.
AB  - The bacterial cell wall, which is comprised of a mesh of polysaccharide strands
      crosslinked via peptide bridges (peptidoglycan, PG), is critical for maintenance
      of cell shape and survival. PG assembly is mediated by a variety of Penicillin
      Binding Proteins (PBP) whose fundamental activities have been characterized in
      great detail; however, there is limited knowledge of the factors that modulate
      their activities in different environments or growth phases. In Vibrio cholerae,
      the cause of cholera, PG synthesis during the transition into stationary phase is
      primarily mediated by the bifunctional enzyme PBP1A. Here, we screened an ordered
      V. cholerae transposon library for mutants that are sensitive to growth
      inhibition by non-canonical D-amino acids (DAA), which prevent growth and
      maintenance of cell shape in PBP1A-deficient V. cholerae. In addition to PBP1A
      and its lipoprotein activator LpoA, we found that CsiV, a small periplasmic
      protein with no previously described function, is essential for growth in the
      presence of DAA. Deletion of csiV, like deletion of lpoA or the PBP1A-encoding
      gene mrcA, causes cells to lose their rod shape in the presence of DAA or the
      beta-lactam antibiotic cefsulodin, and all three mutations are synthetically
      lethal with deletion of mrcB, which encodes PBP1B, V. cholerae's second key
      bifunctional PBP. CsiV interacts with LpoA and PG but apparently not with PBP1A,
      supporting the hypothesis that CsiV promotes LpoA's role as an activator of
      PBP1A, and thereby modulates V. cholerae PG biogenesis. Finally, the requirement
      for CsiV in PBP1A-mediated growth of V. cholerae can be overcome either by
      augmenting PG synthesis or by reducing PG degradation, thereby highlighting the
      importance of balancing these two processes for bacterial survival. 

PMID- 24945692
TI  - Should I pay for your risky behaviours? Evidence from London.
AB  - We investigate the extent to which respondents from a general population sample
      in London (July-August 2011) agree or disagree with the NHS covering the
      healthcare costs related to five risky health behaviours: overeating, unhealthy
      diet, sedentary life, excess of alcohol, and smoking. For each behaviour, we also
      directly explore the main factors associated with the likelihood to agree or
      disagree. Half of the respondents (N=146) manifest agreement with the idea. Wider
      agreement exists for covering the costs associated smoking, heavy drinking, and
      sedentary lives than with overeating, or poor diets. With the exception of
      alcohol drinking and sedentary life, there is an almost one-to-one relationship
      between the agreement that the NHS should pay the healthcare costs associated
      with a specific behaviour, and the respondents' actual engagement in that
      behaviour. Those at higher risk of depending on publicly funded healthcare, are
      more likely to agree. 

PMID- 24945693
TI  - Determinants of Bacillus Calmette-Guerin (BCG) vaccination among Quebec children.
AB  - OBJECTIVES: To identify determinants of Bacillus Calmette-Guerin (BCG)
      vaccination among children born in Quebec, Canada, in 1974, the last year of the
      systematic vaccination campaign. METHOD: A retrospective birth cohort was
      assembled in 2011 through probabilistic linkage of administrative databases
      (n=81,496). Potential determinants were documented from administrative databases
      and by interviewing a subset of subjects (n=1643) in 2012. Analyses were
      conducted among subjects with complete data, 71,658 (88%) birth cohort subjects
      and 1154 (70%) interviewed subjects, then redone using multiple imputation.
      Determinants of BCG vaccination during the organized vaccination program (in
      1974), and after the program (1975 onwards) were assessed separately. Logistic
      regression with backward elimination was used to estimate odds ratios (ORs) and
      95% confidence intervals (CIs). RESULTS: Overall, 46% of subjects were BCG
      vaccinated, 43% during the program and 4% after it ended. BCG vaccination during
      the program was associated with parents' birthplace and urban or rural residence.
      BCG vaccination after the organized program was only related to ethnocultural
      origin of the child's grandparents. CONCLUSION: Different factors were related to
      vaccination within and after the organized program. Determinants of BCG
      vaccination in Quebec, Canada, have never been studied and will be useful for
      future research and vaccination campaigns.

PMID- 24945694
TI  - Cycling-related crash risk and the role of cannabis and alcohol: a case-crossover
      study.
AB  - OBJECTIVE: To examine whether alcohol and cannabis consumption increase crash
      risk among non-fatally injured bicyclists (N=393) seen in three Canadian
      emergency departments, between April 2009 and July 2011. METHOD: Employing a case
      crossover design, cannabis and alcohol were identified through blood sample or by
      self-report. All cyclists involved in a crash and exposure status (cannabis and
      alcohol) were compared between case period (current crash) and two control
      periods: prior to the last time the victim cycled around the same time of day;
      and the typical use prior to bicycling. Crash risk was assessed through
      conditional fixed effects logistic regression models. RESULTS: Approximately 15%
      of cyclists reported using cannabis just prior to the crash, and 14.5% reported
      using alcohol. Cannabis use identified by blood testing or self-report in the
      case period and by self-report in the control period yielded a crash risk of 2.38
      (1.04-5.43); however, when self-report was used for both the case and control
      periods the estimate was 0.40 (0.12-1.27). Alcohol use, as measure either in
      blood or self-report, was associated with an odds ratio of 4.00 (95% CI: 1.64
      9.78); results were similar when alcohol was measured by self-report only.
      CONCLUSION: Cannabis and alcohol use each appear to increase the risk of a non
      fatal injury-related crash among bicyclists, and point to the need for improved
      efforts to deter substance use prior to cycling, with the help of regulation,
      increased education, and greater public awareness. However, cannabis results
      should be interpreted with caution, as the observed association with crash risk
      was contingent on how consumption was measured.

PMID- 24945695
TI  - Are primary care physicians prepared to assist patients for smoking cessation?
      Results of a national Italian cross-sectional web survey.
AB  - OBJECTIVE: The primary purpose of this study is to explore primary care
      physicians' (PCPs') knowledge, attitudes and self-reported activities provided to
      patients for smoking cessation. The secondary purpose is to identify the
      relationships between physician-related characteristics and knowledge, attitudes
      and self-reported activities for smoking cessation. METHOD: A national cross
      sectional web survey was conducted in Italy from April through September 2012.
      RESULTS: 722 PCPs completed the questionnaire. The great majority indicated the
      correct proportion of smokers among patients with lung cancer, the smoking
      abstention required for risk reduction after smoking cessation, and tobacco as a
      known major risk factor for chronic obstructive pulmonary disease (COPD), whereas
      28.7% knew the Fagerstrom test for the assessment of nicotine dependence. Almost
      all PCPs reported that they ask all patients if they smoke, inform about the
      dangers of smoking and recommend to quit smoking, whereas prescription of
      recommended drugs for smoking cessation varied from 37.7% for nicotine
      replacement therapy to 4.9% for varenicline. CONCLUSION: Despite a positive
      attitude, Italian PCPs are not prepared to deliver effective interventions for
      smoking cessation in their patients.

PMID- 24945696
TI  - Readmission penalties and health insurance expansions: a dispatch from
      Massachusetts.
AB  - BACKGROUND: Payers are penalizing hospitals for high readmission rates. It is
      unknown whether major changes in population insurance coverage can affect
      readmission rates, despite the Affordable Care Act's coverage expansions coming
      into effect this year. OBJECTIVE: To evaluate the impact of a large-scale
      insurance expansion on hospital readmissions, using Massachusetts' 2006 health
      reform as a natural experiment. DESIGN: Difference-in-difference time-series
      design. SETTING: All Massachusetts acute-care hospitals. PATIENTS: Inpatient
      visits from 2004 to 2010. MEASUREMENTS: Primary outcome was the hospital 30-day
      readmission rate. Readmissions to any Massachusetts hospital were tracked.
      RESULTS: Decreases in uninsurance rates during and after reform were largely
      limited to the hospital quartile with the highest prereform uninsurance rates
      (from 14% uninsured at the start of the reform to 2.9% by the end of the study
      period). The other hospitals collectively experienced a smaller decline in their
      uninsured admissions (5.9% at the start of reform to 2.5% by the end of the study
      period). According to difference-in-difference regression analysis, the highest
      uninsured hospital quartile experienced a modest increase in their unadjusted
      readmission rate of 0.6 percentage points (95% confidence interval: 0.1%-1.1%)
      during the reform period as compared to the other hospital quartiles (P = 0.01).
      This represents a relative increase of 4.5% in the readmission rate. Risk
      adjusted readmission rates showed no corresponding change. CONCLUSIONS: The
      Affordable Care Act's insurance expansion may be associated with an increase in
      unadjusted readmission rates among hospitals that cared for disproportionate
      numbers of uninsured patients. Risk-adjustment appears to take this effect into
      account.

PMID- 24945698
TI  - Historical pedigree reconstruction from extant populations using PArtitioning of
      RElatives (PREPARE).
AB  - Recent technological improvements in the field of genetic data extraction give
      rise to the possibility of reconstructing the historical pedigrees of entire
      populations from the genotypes of individuals living today. Current methods are
      still not practical for real data scenarios as they have limited accuracy and
      assume unrealistic assumptions of monogamy and synchronized generations. In order
      to address these issues, we develop a new method for pedigree reconstruction,
      [Formula: see text], which is based on formulations of the pedigree
      reconstruction problem as variants of graph coloring. The new formulation allows
      us to consider features that were overlooked by previous methods, resulting in a
      reconstruction of up to 5 generations back in time, with an order of magnitude
      improvement of false-negatives rates over the state of the art, while keeping a
      lower level of false positive rates. We demonstrate the accuracy of [Formula: see
      text] compared to previous approaches using simulation studies over a range of
      population sizes, including inbred and outbred populations, monogamous and
      polygamous mating patterns, as well as synchronous and asynchronous mating. 

PMID- 24945697
TI  - Eliminating rabies in Tanzania? Local understandings and responses to mass dog
      vaccination in Kilombero and Ulanga districts.
AB  - BACKGROUND: With increased global attention to neglected diseases, there has been
      a resurgence of interest in eliminating rabies from developing countries through
      mass dog vaccination. Tanzania recently embarked on an ambitious programme to
      repeatedly vaccinate dogs in 28 districts. To understand community perceptions
      and responses to this programme, we conducted an anthropological study exploring
      the relationships between dogs, society, geography and project implementation in
      the districts of Kilombero and Ulanga, Southern Tanzania. METHODOLOGY/PRINCIPAL
      FINDINGS: Over three months in 2012, we combined the use of focus groups, semi
      structured interviews, a household questionnaire and a population-based survey.
      Willingness to participate in vaccination was mediated by fear of rabies, high
      medical treatment costs and the threat of dog culling, as well as broader notions
      of social responsibility. However, differences between town, rural and (agro-)
      pastoralist populations in livelihood patterns and dog ownership impacted
      coverage in ways that were not well incorporated into project planning. Coverage
      in six selected villages was estimated at 25%, well below official estimates. A
      variety of problems with campaign mobilisation, timing, the location of central
      points, equipment and staff, and project organisation created barriers to
      community compliance. Resource-limitations and institutional norms limited the
      ability for district staff to adapt implementation strategies. CONCLUSIONS AND
      SIGNIFICANCE: In the shadows of resource and institutional limitations in the
      veterinary sector in Africa, top-down interventions for neglected zoonotic
      diseases likes rabies need to more explicitly engage with project organisation,
      capacity and community participation. Greater attention to navigating local
      realities in planning and implementation is essential to ensuring that rabies,
      and other neglected diseases, are controlled sustainably.

PMID- 24945700
TI  - A comparative assessment of economic-incentive and command-and-control
      instruments for air pollution and CO2 control in China's iron and steel sector.
AB  - China's iron and steel sector is faced with increasing pressure to control both
      local air pollutants and CO2 simultaneously. Additional policy instruments are
      needed to co-control these emissions in this sector. This study quantitatively
      evaluates and compares two categories of emission reduction instruments, namely
      the economic-incentive (EI) instrument of a carbon tax, and the command-and
      control (CAC) instrument of mandatory application of end-of-pipe emission control
      measures for CO2, SO2 and NOx. The comparative evaluation tool is an integrated
      assessment model, which combines a top-down computable general equilibrium sub
      model and a bottom-up technology-based sub-model through a soft-linkage. The
      simulation results indicate that the carbon tax can co-control multiple
      pollutants, but the emission reduction rates are limited under the tax rates
      examined in this study. In comparison, the CAC instruments are found to have
      excellent effects on controlling different pollutants separately, but not
      jointly. Such results indicate that no single EI or CAC instrument is
      overwhelmingly superior. The environmental and economic effectiveness of an
      instrument highly depends on its specific attributes, and cannot be predicted by
      the general policy category. These findings highlight the necessity of clearer
      identification of policy target priorities, and detail-oriented and integrated
      policy-making among different governmental departments. 

PMID- 24945701
TI  - Analysis of microbial community adaptation in mesophilic hydrogen fermentation
      from food waste by tagged 16S rRNA gene pyrosequencing.
AB  - Dark fermentation is an attractive process for generation of biohydrogen, which
      involves complex microbial processes on decomposition of organic wastes and
      subsequent conversion of metabolic intermediates to hydrogen. The microbes
      present in an upflow anaerobic sludge blanket (UASB) reactor for waste water
      treatment were tested for application in batch dark fermentation of food waste at
      varying ratios of feedstock to heat-treated microbial inoculum (F/M) of 1-8 (g
      TVS/g TVS). Biohydrogen yields between 0.39 and 2.68 mol H2/mol hexose were
      obtained, indicating that the yields were highly dependent on the starting F/M
      ratio. The highest H2 purity of 66% was obtained from the first 8 h of
      fermentation at the F/M ratio of 2, whereas the highest H2 production was
      obtained after 35 h of fermentation at the F/M ratio of 5. Tagged 16S rRNA gene
      pyrosequencing showed that the seed culture comprised largely of uncultured
      bacteria with various Proteobacteria, Bacteroidetes, and Firmicutes, while the
      starting food waste contained mainly lactic acid bacteria. Enrichment of
      Firmicutes, particularly Clostridia and lactic acid bacteria occurred within 8 h
      of the dark fermentation and the H2 producing microcosm at 35 h was dominated
      >80% by Clostridium spp. The major H2 producer was identified as a Clostridial
      strain related to Clostridium frigidicarnis. This work demonstrated the adaption
      of the microbial community during the dark fermentation of complex food waste and
      revealed the major roles of Clostridia in both substrate degradation and
      biohydrogen production. 

PMID- 24945699
TI  - Competitive ability and fitness differences between two introduced populations of
      the invasive whitefly Bemisia tabaci Q in China.
AB  - BACKGROUND: Our long-term field survey revealed that the Cardinium infection rate
      in Bemisia tabaci Q (also known as biotype Q) population was low in Shandong,
      China over the past few years. We hypothesize that (1) the Cardinium-infected
      (C+) B. tabaci Q population cannot efficiently compete with the Cardinium
      uninfected (C-) B. tabaci Q population; (2) no reproductive isolation may have
      occurred between C+ and C-; and (3) the C- population has higher fitness than the
      C+ population. METHODOLOGY AND RESULTS: To reveal the differences in competitive
      ability and fitness between the two introduced populations (C+ and C-),
      competition between C+ and C- was examined over several generations.
      Subsequently, the reproductive isolation between C+ and C- was studied by
      crossing C+ with C- individuals, and the fitnesses of C+ and C- populations were
      compared using a two-sex life table method. Our results demonstrate that the
      competitive ability of the C+ whiteflies was weaker than that of C-. There is
      that no reproductive isolation occurred between the two populations and the C-
      population had higher fitness than the C+ population. CONCLUSION: The competitive
      ability and fitness differences of two populations may explain why C- whitefly
      populations have been dominant during the past few years in Shandong, China.
      However, the potential role Cardinium plays in whitefly should be further
      explored.

PMID- 24945702
TI  - A new bankruptcy method for conflict resolution in water resources allocation.
AB  - Growing competition over water resources has caused political disputes among
      stakeholders and has brought conflict resolution in the focus of negotiation
      processes. In these cases, bankruptcy rules for redistributing an asset when it
      is not sufficient to meet all claims could be applied. In this paper, we develop
      a new bankruptcy rule for water resources problems that considers agents'
      contribution to the total resources as well as their claims, which is in
      accordance with the UN Watercourses Convention (1997), as important factors for
      reallocation. Using the Euphrates River and a hypothetical case from the
      literature as examples, the new rule is compared with four alternative rules. The
      results show that the novel solution is potentially more powerful to help solving
      conflicts over river sharing problems. 

PMID- 24945703
TI  - Assessing Rural Sustainable Development potentialities using a Dominance-based
      Rough Set Approach.
AB  - Rural Development is a priority in Europe and it is supported by specific,
      financial programmes. At the same time, sustainability is the key word for the
      European Union to construct programmes and policies for all human activities.
      However, measuring sustainability of rural areas is not easy, due to their
      particular features. The improvement of knowledge on sustainability in rural
      areas is important to build long term policies and strategies for those
      territories. The objective of this study is the development of a decision support
      system based on the Dominance-based Rough Set Approach (DRSA), to assess the
      level of Rural Sustainable Development in specific areas. We used DRSA to analyze
      the level of sustainability of the 92 municipalities of the Region of Umbria,
      Italy. The results were synthesized in a final ranking, taking into account the
      equilibrium and the integration between development and sustainability of each
      municipality. DRSA showed a high potential in the context of management or
      planning, and for supporting Decision Makers. DRSA is able to give a ranking as
      well as an explanation of the main factors driving sustainable development in
      rural areas. 

PMID- 24945704
TI  - Systematic review of economic evaluation of laparotomy versus laparoscopy for
      patients submitted to Roux-en-Y gastric bypass.
AB  - BACKGROUND: Because of the high prevalence of obesity, there is a growing demand
      for bariatric surgery worldwide. The objective of this systematic review was to
      analyze the difference in relation to cost-effectiveness of access route by
      laparoscopy versus laparotomy of Roux en-Y gastric bypass (RYGB). METHODS: A
      systematic review was conducted in the electronic databases MEDLINE, Embase,
      Scopus, Cochrane and Lilacs in order to identify economic evaluation studies that
      compare the cost-effectiveness of laparoscopic and laparotomic routes in RYGB.
      RESULTS: In a total of 494 articles, only 6 fulfilled the eligibility criteria.
      All studies were published between 2001 and 2008 in the United States (USA).
      Three studies fulfilled less than half of the items that evaluated the results
      quality; two satisfied 5 of the required items, and only 1 study fulfilled 7 of
      10 items. The economic evaluation of studies alternated between cost
      effectiveness and cost-consequence. Five studies considered the surgery by
      laparoscopy the dominant strategy, because it showed greater clinical benefit
      (less probability of post-surgical complications, less hospitalization time) and
      lower total cost. CONCLUSION: This review indicates that laparoscopy is a safe
      and well-tolerated technique, despite the costs of surgery being higher when
      compared with laparotomy. However, the additional costs are compensated by the
      lower probability of complications after surgery and, consequently, avoiding
      their costs.

PMID- 24945705
TI  - Hydration and chain entanglement determines the optimum thickness of poly(HEMA-co
      PEG10MA) brushes for effective resistance to settlement and adhesion of marine
      fouling organisms.
AB  - Understanding how surface physicochemical properties influence the settlement and
      adhesion of marine fouling organisms is important for the development of
      effective and environmentally benign marine antifouling coatings. We demonstrate
      that the thickness of random poly(HEMA-co-PEG10MA) copolymer brushes affect
      antifouling behavior. Films of thicknesses ranging from 50 to 1000 A were
      prepared via surface-initiated atom-transfer radical polymerization and
      characterized using infrared spectroscopy, ellipsometry, atomic force microscopy
      and contact angle measurements. The fouling resistance of these films was
      investigated by protein adsorption, attachment of the marine bacterium Cobetia
      marina, settlement and strength of attachment tests of zoospores of the marine
      alga Ulva linza and static immersion field tests. These assays show that the
      polymer film thickness influenced the antifouling performance, in that there is
      an optimum thickness range, 200-400 A (dry thickness), where fouling of all
      types, as well as algal spore adhesion, was lower. Field test results also showed
      lower fouling within the same thickness range after 2 weeks of immersion. Studies
      by quartz crystal microbalance with dissipation and underwater captive bubble
      contact angle measurements show a strong correlation between lower fouling and
      higher hydration, viscosity and surface energy of the poly(HEMA-co-PEG10MA)
      brushes at thicknesses around 200-400 A. We hypothesize that the reduced
      antifouling performance is caused by a lower hydration capacity of the polymer
      for thinner films, and that entanglement and crowding in the film reduces the
      conformational freedom, hydration capacity and fouling resistance for thicker
      films. 

PMID- 24945707
TI  - Atomic structure and dynamics of metal dopant pairs in graphene.
AB  - We present an atomic resolution structural study of covalently bonded dopant
      pairs in the lattice of monolayer graphene. Two iron (Fe) metal atoms that are
      covalently bonded within the graphene lattice are observed and their interaction
      with each other is investigated. The two metal atom dopants can form small paired
      clusters of varied geometry within graphene vacancy defects. The two Fe atoms are
      created within a 10 nm diameter predefined location in graphene by manipulating a
      focused electron beam (80 kV) on the surface of graphene containing an
      intentionally deposited Fe precursor reservoir. Aberration-corrected transmission
      electron microscopy at 80 kV has been used to investigate the atomic structure
      and real time dynamics of Fe dimers embedded in graphene vacancies. Four
      different stable structures have been observed; two variants of an Fe dimer in a
      graphene trivacancy, an Fe dimer embedded in two adjacent monovacancies and an Fe
      dimer trapped by a quadvacancy. According to spin-sensitive DFT calculations,
      these dimer structures all possess magnetic moments of either 2.00 or 4.00 MUB.
      The dimer structures were found to evolve from an initial single Fe atom dopant
      trapped in a graphene vacancy.

PMID- 24945706
TI  - Demonstration of an ethane spectrometer for methane source identification.
AB  - Methane is an important greenhouse gas and tropospheric ozone precursor.
      Simultaneous observation of ethane with methane can help identify specific
      methane source types. Aerodyne Ethane-Mini spectrometers, employing recently
      available mid-infrared distributed feedback tunable diode lasers (DFB-TDL),
      provide 1 s ethane measurements with sub-ppb precision. In this work, an Ethane
      Mini spectrometer has been integrated into two mobile sampling platforms, a
      ground vehicle and a small airplane, and used to measure ethane/methane
      enhancement ratios downwind of methane sources. Methane emissions with precisely
      known sources are shown to have ethane/methane enhancement ratios that differ
      greatly depending on the source type. Large differences between biogenic and
      thermogenic sources are observed. Variation within thermogenic sources are
      detected and tabulated. Methane emitters are classified by their expected ethane
      content. Categories include the following: biogenic (<0.2%), dry gas (1-6%), wet
      gas (>6%), pipeline grade natural gas (<15%), and processed natural gas liquids
      (>30%). Regional scale observations in the Dallas/Fort Worth area of Texas show
      two distinct ethane/methane enhancement ratios bridged by a transitional region.
      These results demonstrate the usefulness of continuous and fast ethane
      measurements in experimental studies of methane emissions, particularly in the
      oil and natural gas sector. 

PMID- 24945708
TI  - Enhanced MC3T3-E1 preosteoblast response and bone formation on the addition of
      nano-needle and nano-porous features to microtopographical titanium surfaces.
AB  - Micro/nanotopographical modifications on titanium surfaces constitute a new
      process to increase osteoblast response to enhance bone formation. In this study,
      we utilized alkali heat treatment at high (SB-AH1) and low temperatures (SB-AH2)
      to nano-modify sandblasted titanium with microtopographical surfaces. Then, we
      evaluated the surface properties, biocompatibility and osteogenic capability of
      SB-AH1 and SB-AH2 in vitro and in vivo, and compared these with conventional
      sandblast-acid etching (SLA) and Ti control surfaces. SB-AH1 and SB-AH2 surfaces
      exhibited micro/nanotopographical modifications of nano-needle structures and
      nano-porous network layers, respectively, compared with the sole
      microtopographical surface of macro and micro pits on the SLA surface and the
      relatively smooth surface on the Ti control. SB-AH1 and SB-AH2 showed different
      roughness and elemental components, but similar wettability. MC3T3-E1
      preosteoblasts anchored closely on the nanostructures of SB-AH1 and SB-AH2
      surfaces, and these two surfaces more significantly enhanced cell proliferation
      and alkaline phosphatase (ALP) activity than others, while the SB-AH2 surface
      exhibited better cell proliferation and higher ALP activity than SB-AH1. All four
      groups of titanium domes with self-tapping screws were implanted in rabbit
      calvarial bone models, and these indicated that SB-AH1 and SB-AH2 surfaces
      achieved better peri-implant bone formation and implant stability, while the SB
      AH2 surface achieved the best percentage of bone-implant contact (BIC%). Our
      study demonstrated that the micro/nanotopographical surface generated by
      sandblasting and alkali heat treatment significantly enhanced preosteoblast
      proliferation, ALP activity and bone formation in vitro and in vivo, and nano
      porous network topography may further induce better preosteoblast proliferation,
      ALP activity and BIC%. 

PMID- 24945709
TI  - Aseptic arachnoiditis in a patient treated with intrathecal morphine infusion:
      symptom resolution on switch to ziconotide.
AB  - INTRODUCTION: Since 1980, about 95,000 intrathecal (IT) drug delivery pumps have
      been implanted for the administration of a variety of opioid and non-opioid
      agents for neuropathic and nociceptive pain patients. IT granuloma in chronic
      opioid infusion is becoming less rare as an adverse effect of IT therapy and has
      been associated with many analgesic infusion agents. MATERIALS AND METHODS: After
      thymectomy, upper left lobectomy, and pericardial resection, our patient
      developed a left hemithorax nociceptive pain. An IT catheter and infusion pump
      were implanted, providing adequate analgesia. After eight months, the patient
      developed pain in the lower extremities without neurological impairment and an
      urge to move the legs without meningeal signs (3.2 mg morphine/day). A lumbar
      puncture revealed an inflammatory reaction in the cerebrospinal fluid (CSF);
      neuroimaging results were negative for granuloma. Reduction in morphine dose and
      a switch to ziconotide infusion were carried out. Nine months after the switch,
      CSF test values were in normal ranges. The patient described ongoing benefit in
      terms of pain and walking ability. RESULTS: The patient reported restless legs
      and leg pain, causing insomnia and necessitating an increase in IT opioid dose.
      After the switch to ziconotide and morphine discontinuation, inflammatory
      reactions and symptoms in the CSF abated. CONCLUSIONS: CSF analysis should be
      performed in patients chronically treated by IT infusion who develop a rapid
      increase in pain with or without neurological deficits. A switch to ziconotide
      can be an option in patients without neurological signs. Further studies are
      needed to determine the relationship between granuloma formation and CSF
      reaction.

PMID- 24945710
TI  - Concentric macular rings sign in patients with foveal hypoplasia.
AB  - IMPORTANCE: We describe a sign that can be used as a rapid and noninvasive
      adjunct to aid in the diagnosis of foveal hypoplasia. OBJECTIVE: To describe a
      concentric macular rings sign found on infrared reflectance (IRR) images in
      patients with foveal hypoplasia. DESIGN, SETTING, AND PATIENTS: We studied 13
      patients with foveal hypoplasia (7 with ocular albinism [OA], 5 with
      oculocutaneous albinism [OCA], and 1 with aniridia) at a tertiary ophthalmology
      center with access to electrodiagnostic services from February 18, 2009, through
      April 9, 2013. MAIN OUTCOMES AND MEASURES: All patients and an age-matched
      control participant underwent a complete clinical examination,
      electroretinography (full field and pattern), visual evoked potentials, fundus
      autofluorescence IRR, and optical coherence tomography (OCT). One patient with OA
      and the control participant also underwent scanning laser polarimetry with
      variable corneal compensation (GDx VCC). RESULTS: Thirteen patients (6 girls and
      7 boys), with a mean age of 5.8 years (range, 3-11 years), were included in the
      study. Seven patients were diagnosed as having OA and had minimal clinical signs
      (fine nystagmus in 2 patients and subtle iris transillumination in 5 patients).
      Five patients with OCA and 1 with aniridia were also included. In 12 patients, OA
      and OCA were confirmed with 5-channel visual evoked potentials (optic nerve
      misrouting). Whenever OCT was performed, foveal hypoplasia was indicated by the
      lack of foveal dip. The macula lacked the foveal attenuation normally seen with
      fundus autofluorescence, and a concentric macular rings reflex was seen with IRR
      in all 13 patients and with GDx VCC in 1 patient. A normal bowtie reflex was seen
      with IRR and GDx VCC in the age-matched control participant. CONCLUSIONS AND
      RELEVANCE: Our findings suggest that concentric macular rings seen on IRR or GDx
      VCC can occur in patients with foveal hypoplasia and can therefore aid in the
      diagnosis, especially in patients with minimal clinical signs (mild OA) or in
      cases in which OCT cannot be performed (young patients or patients with high
      amplitude nystagmus).

PMID- 24945712
TI  - The impact of alexithymia on burnout amongst relatives of people who suffer from
      traumatic brain injury.
AB  - BACKGROUND: Although previous research has provided some indication of the
      association of alexithymia and burnout, this is the first study exploring the
      association of these two variables in a sample of relatives of individuals who
      have sustained traumatic brain injury (TBI). OBJECTIVE: To explore the degree to
      which relatives experience burnout and the extent to which alexithymia acts as a
      pre-disposing factor, controlling for depression and coping strategies. METHOD:
      Toronto Alexithymia Scale-20, Maslach Burnout Inventory-Human Services, Estonian
      COPE Dispositional Inventory and Beck Depression Inventory-II were completed by
      60 relatives of patients with TBI drawn from a tertiary head injury clinic
      population. RESULTS: Levels of emotional exhaustion, reduced personal
      accomplishment and depression were significantly higher in the sub-group of
      relatives with alexithymia than in the sub-group of relatives without
      alexithymia. Difficulty describing feelings and externally oriented thinking
      style were significant predictors of emotional exhaustion, while difficulty
      identifying feelings and difficulty describing feelings were important predictors
      of depersonalization. CONCLUSIONS: Relatives who present with alexithymia need to
      be identified at an early stage to minimize risks of burnout leading to adverse
      effects on patient-caregiver relationships.

PMID- 24945714
TI  - Acclimation to UV-B radiation and visible light in Lactuca sativa involves up
      regulation of photosynthetic performance and orchestration of metabolome-wide
      responses.
AB  - UV-B radiation is often viewed as a source of stress for higher plants. In
      particular, photosynthetic function has been described as a common target for UV
      B impairment; yet as our understanding of UV-B photomorphogenesis increases,
      there are opportunities to expand the emerging paradigm of regulatory UV
      response. Lactuca sativa is an important dietary crop species and is often
      subjected to rapid sunlight exposure at field transfer. Acclimation to UV-B and
      visible light conditions in L. sativa was dissected using gas exchange and
      chlorophyll fluorescence measurements, in addition to non-destructive assessments
      of UV epidermal shielding (SUV ). After UV-B treatment, seedlings were subjected
      to wide-range metabolomic analysis using liquid chromatography hybrid quadrupole
      time-of-flight high-resolution mass spectrometry (LC-QTOF-HRMS). During the
      acclimation period, net photosynthetic rate increased in UV-treated plants,
      epidermal UV shielding increased in both subsets of plants transferred to the
      acclimatory conditions (UV+/UV- plants) and Fv /Fm declined slightly in UV+/UV-
      plants. Metabolomic analysis revealed that a key group of secondary compounds was
      up-regulated by higher light conditions, yet several of these compounds were
      elevated further by UV-B radiation. In conclusion, acclimation to UV-B radiation
      involves co-protection from the effects of visible light, and responses to UV-B
      radiation at a photosynthetic level may not be consistently viewed as damaging to
      plant development. 

PMID- 24945711
TI  - Toxoplasma gondii profilin promotes recruitment of Ly6Chi CCR2+ inflammatory
      monocytes that can confer resistance to bacterial infection.
AB  - Ly6C+ inflammatory monocytes are essential to host defense against Toxoplasma
      gondii, Listeria monocytogenes and other infections. During T. gondii infection
      impaired inflammatory monocyte emigration results in severe inflammation and
      failure to control parasite replication. However, the T. gondii factors that
      elicit these monocytes are unknown. Early studies from the Remington laboratory
      showed that mice with a chronic T. gondii infection survive lethal co-infections
      with unrelated pathogens, including L. monocytogenes, but a mechanistic analysis
      was not performed. Here we report that this enhanced survival against L.
      monocytogenes is due to early reduction of bacterial burdens and elicitation of
      Ly6C+ inflammatory monocytes. We demonstrate that a single TLR11/TLR12 ligand
      profilin (TgPRF) was sufficient to reduce bacterial burdens similar to T. gondii
      chronic infection. Stimulation with TgPRF was also sufficient to enhance animal
      survival when administered either pre- or post-Listeria infection. The ability of
      TgPRF to reduce L. monocytogenes burdens was dependent on TLR11 and required IFN
      gamma but was not dependent on IL-12 signaling. TgPRF induced rapid production of
      MCP-1 and resulted in trafficking of Ly6Chi CCR2+ inflammatory monocytes and
      Ly6G+ neutrophils into the blood and spleen. Stimulation with TgPRF reduced L.
      monocytogenes burdens in mice depleted with the Ly6G specific MAb 1A8, but not in
      Ly6C/Ly6G specific RB6-8C5 depleted or CCR2-/- mice, indicating that only
      inflammatory monocytes are required for TgPRF-induced reduction in bacterial
      burdens. These results demonstrate that stimulation of TLR11 by TgPRF is a
      mechanism to promote the emigration of Ly6Chi CCR2+ monocytes, and that TgPRF
      recruited inflammatory monocytes can provide an immunological benefit against an
      unrelated pathogen. 

PMID- 24945716
TI  - Aligning HIV/AIDS communication with the oral tradition of Africans: a theory
      based content analysis of songs' potential in prevention efforts.
AB  - Despite a growing recognition of songs as a useful HIV/AIDS campaign strategy,
      little research has investigated their potential and/or actual impact. In this
      study, through a theory-based content analysis, we have assessed the prevention
      domains covered and the health-relevant constructs promoted by 23 AIDS songs
      widely used to aid prevention efforts in Ethiopia. To identify the health
      relevant constructs and reveal their potential to facilitate or inhibit positive
      changes, the Extended Parallel Process Model (EPPM) has been used. The findings
      revealed that the songs cover most of the prevention domains that constitute the
      current agenda of behavior change communication in Sub-Saharan Africa. However,
      although all the EPPM variables have been found in almost every song, there were
      significantly more efficacy messages than threat messages. This suggests that
      although the songs may lead to positive changes in HIV/AIDS-related outcomes
      among audiences who have already perceived the threat posed by HIV/AIDS, they are
      less likely to motivate and thereby generate responses from audiences who have
      less or no threat perceptions. It is argued that given their potential as a
      culturally appropriate strategy in Sub-Saharan Africa where oral channels of
      communication play significant roles, songs could be harnessed for better
      outcomes through a theory-based design. 

PMID- 24945715
TI  - Effects of short-term energy deficit on muscle protein breakdown and
      intramuscular proteolysis in normal-weight young adults.
AB  - The effects of short-term energy deficit (ED) on direct measures of muscle
      proteolysis and the intracellular mechanisms by which muscle proteins are
      degraded at rest and following aerobic exercise are not well described. This
      study evaluated the effects of a short-term diet-induced ED, on muscle fractional
      breakdown rate (FBR), intramuscular 26S proteasome activity, caspase-3
      activation, and PSMA2 and MAFbx expression at rest, in the postabsorptive state,
      and following a single bout of moderate aerobic exercise (45 min at 65% peak
      oxygen uptake). Six men and 4 women participated in two 10-day diet
      interventions: weight maintenance (WM) followed by ED (80% estimated energy
      requirements). Dietary protein (1.5 g.kg(-1).day(-1)) intake was constant for WM
      and ED. Mixed muscle FBR, proteasome activity, and intracellular proteolytic
      factor expression were measured using stable isotope methodology, fluorescent
      enzyme activity assays, and Western blotting, respectively. Overall, FBR and
      caspase-3 activation increased 60% and 11%, respectively, in response to ED (P <
      0.05), but were not influenced by exercise. During ED, 26S proteasome alpha
      subunit PSMA2 expression was 25% higher (P < 0.05) after exercise compared with
      rest. Exercise did not influence PSMA2 expression during WM, and MAFbx expression
      and 26S proteasome activity were not affected by ED or exercise. These data
      illustrate the effects of short-term, moderate ED on muscle protein degradation.
      In the context of skeletal muscle integrity during weight loss interventions,
      this work demonstrates a need for further investigations aimed at mitigating
      muscle loss associated with energy deficit imposed for intentional reduction of
      total body weight. 

PMID- 24945719
TI  - Prediction model for penile prosthesis implantation for erectile dysfunction
      management.
AB  - OBJECTIVE: Penile prosthesis surgery is indicated based on undesirability,
      contraindication or ineffectiveness of non-surgical options for erectile
      dysfunction. This definitive treatment is often delayed after initial diagnosis.
      Our objective was to develop a prediction tool based on a patient's clinical
      history to determine likelihood of ultimately receiving a penile prosthesis.
      RESEARCH DESIGN AND METHODS: This retrospective analysis used claims data from
      Commercial and Medicare supplemental databases. Inclusion criteria were 18 years
      of age with 1 year of continuous enrollment at the first diagnosis of erectile
      dysfunction. Patients' demographics, co-morbidities and erectile dysfunction
      therapy were derived based on enrollment, medical and prescription histories.
      MAIN OUTCOME MEASURES: The Cox proportional hazards model with stepwise selection
      was used to identify and quantify (using relative risk) factors associated with a
      future penile prosthesis implant. Co-morbidities and therapies present prior to
      the index erectile dysfunction diagnosis were analyzed as fixed covariates.
      RESULTS: Approximately 1% of the dataset's population (N = 310,303 Commercial, N
      = 74,315 Medicare, respectively) underwent penile prosthesis implantation during
      the study period (3928 patients in the overall population: 2405 patients [0.78%]
      in the Commercial and 1523 patients [2.05%] in the Medicare population). Factors
      with the greatest predictive strength of penile prosthesis implantation included
      prostate cancer diagnosis (relative risk: 3.93, 2.29; 95% CI, 3.57-4.34, 2.03
      2.6), diabetes mellitus (2.31, 1.23; 2.12-2.52, 1.1-1.37) and previous treatment
      with first-line therapy (1.39, 1.33; 1.28-1.5, 1.2-1.47) (all P < 0.01).
      CONCLUSION: The presence and extent of specific medical history factors at the
      time of erectile dysfunction diagnosis predict an individual's future likelihood
      of penile prosthesis. Calculating the likelihood of penile prosthesis
      implantation based on the weight of these factors may assist clinicians with the
      definition of a care plan and patient counseling. The precision of the model may
      be limited by factors beyond medical history information that possibly influence
      the decision to proceed to surgery.

PMID- 24945718
TI  - A complex equilibrium among partially unfolded conformations in monomeric
      transthyretin.
AB  - Aggregation of transthyretin (TTR) is known to be linked to the development of
      systemic and localized amyloidoses. It also appears that TTR exerts a protective
      role against aggregation of the Abeta peptide, a process linked to Alzheimer's
      disease. In vitro, both processes correlate with the ability of TTR to populate a
      monomeric state, yet a complete description of the possible conformational states
      populated by monomeric TTR in vitro at physiological pH is missing. Using an
      array of biophysical methods and kinetic tests, we show that once monomers of
      transthyretin are released from the tetramer, equilibrium is established between
      a set of conformational states possessing different degrees of disorder. A molten
      globular state appears in equilibrium with the fully folded monomer, whereas an
      off-pathway species accumulates transiently during refolding of TTR. These two
      conformational ensembles are distinct in terms of structure, kinetics, and their
      pathways of formation. Further subpopulations of the protein fold differently
      because of the occurrence of proline isomerism. The identification of
      conformational states unrevealed in previous studies opens the way for further
      characterization of the amyloidogenicity of TTR and its protective role in
      Alzheimer's disease. 

PMID- 24945717
TI  - Attachment anxiety is related to Epstein-Barr virus latency.
AB  - Attachment theory provides a framework for understanding individual differences
      in chronic interpersonal stress. Attachment anxiety, a type of relationship
      insecurity characterized by worry about rejection and abandonment, is a chronic
      interpersonal stressor. Stress impacts cellular immunity, including herpesvirus
      reactivation. We investigated whether attachment anxiety was related to the
      expression of a latent herpesvirus, Epstein-Barr virus (EBV), when individuals
      were being tested for breast or colon cancer and approximately 1 year later.
      Participants (N=183) completed a standard attachment questionnaire and provided
      blood to assess EBV viral capsid antigen (VCA) IgG antibody titers. Individuals
      with more attachment anxiety had higher EBV VCA IgG antibody titers than those
      with less attachment anxiety. The strength of the association between attachment
      anxiety and antibody titers was the same at both assessments. This study is the
      first to show an association between latent herpesvirus reactivation and
      attachment anxiety. Because elevated herpesvirus antibody titers reflect poorer
      cellular immune system control over the latent virus, these data suggest that
      high attachment anxiety is associated with cellular immune dysregulation.

PMID- 24945720
TI  - Severe hypoglycemia rates and associated costs among type 2 diabetics starting
      basal insulin therapy in the United States.
AB  - OBJECTIVES: To derive current real-world data on the rates and costs of severe
      hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have
      initiated basal insulin therapy and to examine differences in SH rates and costs
      stratified by history of prior SH events. METHODS: We used a nation-wide
      electronic health records database that included encounter and laboratory data,
      as well as clinical notes, to estimate the rates and costs of SH events among
      adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and
      regression-adjusted rates and quarterly costs were calculated for all patients as
      well as stratified by history of a SH event before starting basal insulin and
      history of a SH event during the basal insulin titration period. RESULTS: We
      identified 7235 incident cases of basal insulin use among patients with T2D who
      did not use insulin during the previous 12 months. Regression-adjusted incidence
      and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A
      history of SH events during the pre-index baseline and post-index titration
      periods were statistically significantly associated with both the incidence and
      total event rates (p < 0.01). Regression-adjusted total healthcare and diabetes
      related costs were statistically significantly (p < 0.01) higher in those
      quarters when a SH event occurred than in those quarters without any SH events
      ($3591 vs. $487 and $3311 vs. $406, respectively). A history of previous SH or SH
      events during the titration period were not statistically significantly
      associated with costs. CONCLUSIONS: These results suggest that the real-world
      burden of SH is high among people with T2D who start using basal insulin and that
      history of previous SH events, both before starting insulin and during the
      insulin titration period, influences future SH. These results can also provide
      insights into interventions that can prevent or delay SH. These results should,
      however, be interpreted in light of the key limitations of our study: not all SH
      events may have been captured or coded in the database, data on filled
      prescriptions were not available, and the post-titration follow-up period could
      have been divided into time units other than quarters (3 month blocks) resulting
      in potentially different conclusions. Further real-world studies on the frequency
      and costs of SH, using methods to identify as many SH events as possible, can
      allow healthcare providers to make more informed decisions on the risks and
      benefits of basal insulin therapy in T2D patients.

PMID- 24945721
TI  - The impact of the quality of communication from nephrologists to primary care
      practitioners: a literature review.
AB  - OBJECTIVE: This review of the literature aims to explore two research questions:
      (1) what is the evidence that patients benefit from sound communication between
      primary care practitioners (PCPs) and nephrologists; and (2) what information is
      required in primary care to meet the needs of patients who have attended a renal
      unit? RESEARCH DESIGN AND METHODS: Fifty-seven citations were independently
      reviewed by four authors. The inclusion criteria were: (1) the article focused on
      information flow from nephrologists and/or specialists to general practitioners;
      (2) it includes the involvement of PCPs in nephrology, including registrars and
      PCPs with special interests or specialists in any medical field; (3) it was
      published from 1990 onwards (inclusive) and (4) the study was conducted in the
      United Kingdom, Canada, The Netherlands, Australia, United States or New Zealand.
      Selected articles were then reviewed by the fifth author as a measure of inter
      rater reliability. RESULTS: Eighteen papers in four categories were identified:
      six audits or observational studies, one meta-analysis; one randomized controlled
      trial; six qualitative studies; and four position statements or quality
      improvement tools. Published audits involving feedback to clinicians using
      validated tools demonstrate the scope for substantial improvement in the amount
      of information relayed to PCPs. Specialists may not prioritize the letter to the
      PCP but there is some evidence of a direct impact from limited or inadequate
      communication on patient outcomes. Only two studies focused on patients attending
      nephrology clinics. CONCLUSIONS: There is some evidence that improving the
      quality of letters from specialists to PCPs may benefit patient care. This review
      suggests a need for research on communication from nephrologists about patients
      who have received care at a renal unit regardless of whether or not the patient
      continues to attend.

PMID- 24945724
TI  - Photochemical pump and NMR probe: chemically created NMR coherence on a
      microsecond time scale.
AB  - We report pump-probe experiments employing laser-synchronized reactions of para
      hydrogen (para-H2) with transition metal dihydride complexes in conjunction with
      nuclear magnetic resonance (NMR) detection. The pump-probe experiment consists of
      a single nanosecond laser pump pulse followed, after a precisely defined delay,
      by a single radio frequency (rf) probe pulse. Laser irradiation eliminates H2
      from either Ru(PPh3)3(CO)(H)2 1 or cis-Ru(dppe)2(H)2 2 in C6D6 solution. Reaction
      with para-H2 then regenerates 1 and 2 in a well-defined nuclear spin state. The
      rf probe pulse produces a high-resolution, single-scan (1)H NMR spectrum that can
      be recorded after a pump-probe delay of just 10 MUs. The evolution of the spectra
      can be followed as the pump-probe delay is increased by micro- or millisecond
      increments. Due to the sensitivity of this para-H2 experiment, the resulting NMR
      spectra can have hydride signal-to-noise ratios exceeding 750:1. The spectra of 1
      oscillate in amplitude with frequency 1101 +/- 3 Hz, the chemical shift
      difference between the chemically inequivalent hydrides. The corresponding
      hydride signals of 2 oscillate with frequency 83 +/- 5 Hz, which matches the
      difference between couplings of the hydrides to the equatorial (31)P nuclei. We
      use the product operator formalism to show that this oscillatory behavior arises
      from a magnetic coherence in the plane orthogonal to the magnetic field that is
      generated by use of the laser pulse without rf initialization. In addition, we
      demonstrate how chemical shift imaging can differentiate the region of laser
      irradiation thereby distinguishing between thermal and photochemical reactivity
      within the NMR tube. 

PMID- 24945723
TI  - Alterations in leukocyte telomere length in workers occupationally exposed to
      benzene.
AB  - Exposure to benzene, a known leukemogen and probable lymphomagen, has been
      demonstrated to result in oxidative stress, which has previously been associated
      with altered telomere length (TL). TL specifically has been associated with
      several health outcomes in epidemiologic studies, including cancer risk, and has
      been demonstrated to be altered following exposure to a variety of chemical
      agents. To evaluate the association between benzene exposure and TL, we measured
      TL by monochrome multiplex quantitative PCR in 43 workers exposed to high levels
      of benzene and 43 age and sex-matched unexposed workers in Shanghai, China.
      Benzene exposure levels were monitored using organic vapor passive dosimetry
      badges before phlebotomy. The median benzene exposure level in exposed workers
      was 31 ppm. The mean TL in controls, workers exposed to levels of benzene below
      the median (<=31 ppm), and above the median (>31 ppm) was 1.26 +/- 0.17, 1.25 +/-
      0.16, and 1.37 +/- 0.23, respectively. Mean TL was significantly elevated in
      workers exposed to >31 ppm of benzene compared with controls (P = 0.03). Our
      findings provide evidence that high levels of occupational benzene exposure are
      associated with TL. Environ.

PMID- 24945722
TI  - A genome-wide tethering screen reveals novel potential post-transcriptional
      regulators in Trypanosoma brucei.
AB  - In trypanosomatids, gene expression is regulated mainly by post-transcriptional
      mechanisms, which affect mRNA processing, translation and degradation. Currently,
      our understanding of factors that regulate either mRNA stability or translation
      is rather limited. We know that often, the regulators are proteins that bind to
      the 3'-untranslated region; they presumably interact with ribonucleases and
      translation factors. However, very few such proteins have been characterized in
      any detail. Here we describe a genome-wide screen to find proteins implicated in
      post-transcriptional regulation in Trypanosoma brucei. We made a library of
      random genomic fragments in a plasmid that was designed for expression of
      proteins fused to an RNA-binding domain, the lambda-N peptide. This was
      transfected into cells expressing mRNAs encoding a positive or negative
      selectable marker, and bearing the "boxB" lambda-N recognition element in the 3'
      untranslated region. The screen identified about 300 proteins that could be
      implicated in post-transcriptional mRNA regulation. These included known
      regulators, degradative enzymes and translation factors, many canonical RNA
      binding proteins, and proteins that act via multi-protein complexes. However
      there were also nearly 150 potential regulators with no previously annotated
      function, or functions unrelated to mRNA metabolism. Almost 50 novel regulators
      were shown to bind RNA using a targeted proteome array. The screen also provided
      fine structure mapping of the hit candidates' functional domains. Our findings
      not only confirm the key role that RNA-binding proteins play in the regulation of
      gene expression in trypanosomatids, but also suggest new roles for previously
      uncharacterized proteins. 

PMID- 24945725
TI  - Di-tyrosine cross-link decreases the collisional cross-section of abeta peptide
      dimers and trimers in the gas phase: an ion mobility study.
AB  - Oligomeric forms of Abeta peptide are most likely the main synaptotoxic and
      neurotoxic agent in Alzheimer's disease. Toxicity of various Abeta oligomeric
      forms has been confirmed in vivo and also in vitro. However, in vitro
      preparations were found to be orders of magnitude less toxic than oligomers
      obtained from in vivo sources. This difference can be explained by the presence
      of a covalent cross-link, which would stabilize the oligomer. In the present
      work, we have characterized the structural properties of Abeta dimers and trimers
      stabilized by di- and tri-tyrosine cross-links. Using ion mobility mass
      spectrometry we have compared the collisional cross-section of non-cross-linked
      and cross-linked species. We have found that the presence of cross-links does not
      generate new unique forms but rather shifts the equilibrium towards more compact
      oligomer types that can also be detected for non-cross-linked peptide. In
      consequence, more extended forms, probable precursors of off-pathway oligomeric
      species, become relatively destabilized in cross-linked oligomers and the pathway
      of oligomer evolution becomes redirected towards fibrillar structures. 

PMID- 24945726
TI  - SLCO3A1, A novel crohn's disease-associated gene, regulates nf-kappaB activity
      and associates with intestinal perforation.
AB  - BACKGROUND & AIMS: To date, only one gene (TNFSF15) has been identified and
      validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations.
      This study was designed to identify novel CD-associated single nucleotide
      polymorphisms (SNPs)/genes and to validate candidate genes using a functional
      assay. METHODS: SNPs from 16 CD patients and 16 age- and sex-matched control
      patients were analyzed using Illumina platform analysis. Subsequently, we
      expanded the study and followed 53 CD patients and 41 control patients by
      Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining
      were performed to assess mRNA and protein expression of the candidate gene on
      tissue isolated from CD patients. Genotype was correlated with CD phenotypes.
      Finally, the candidate gene was cloned and its effect on NF-kappaB activity
      assessed using a reporter luciferase assay. RESULTS: SLCO3A1 (rs207959) reached
      statistical significance in the first-stage analysis (P = 2.3E-02) and was
      further validated in the second-stage analysis (P = 1.0E-03). Genotype and
      phenotype analysis showed that the rs207959 (T) allele is a risk allele that
      alters SLCO3A1 mRNA expression and is associated with intestinal perforation in
      CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in
      CD patients compared with the control group. Overexpression of SLCO3A1 induced
      increased NF-kappaB activity and increased phosphorylation of P65, ERK, and JNK.
      Nicotine augmented the activation of NF-kappaB in the presence of SLCO3A1.
      CONCLUSIONS: SLCO3A1, a novel CD-associated gene, mediates inflammatory processes
      in intestinal epithelial cells through NF-kappaB transcription activation,
      resulting in a higher incidence of bowel perforation in CD patients.

PMID- 24945727
TI  - Association of 677 C>T (rs1801133) and 1298 A>C (rs1801131) polymorphisms in the
      MTHFR gene and breast cancer susceptibility: a meta-analysis based on 57
      individual studies.
AB  - OBJECTIVE: The 677 C>T and 1298 A>C polymorphisms of methylenetetrahydrofolate
      reductase (MTHFR) gene have been widely reported and considered to have a
      significant effect on breast cancer risk, but the results are inconsistent. A
      meta-analysis based on 57 eligible studies was carried out to clarify the role of
      MTHFR gene polymorphisms in breast cancer. METHODS AND RESULTS: Eligible articles
      were identified by searching databases including PubMed, Web of Science, EMBASE,
      CNKI and CBM for the period up to August 2012. Finally, a total of 57 studies
      were included in this meta-analysis. Crude ORs with 95% CIs were used to assess
      the association between the MTHFR polymorphisms and breast cancer risk. The
      pooled ORs were performed with additive model, dominant model and recessive
      model, respectively. Subgroup analysis was also performed by ethnicity. The
      statistical heterogeneity across studies was examined with chi2-based Q-test. A
      meta-analysis was performed using the Stata 12.0 software. Overall, the 677 C
      allele was significantly associated with breast cancer risk (OR = 0.942, 95%CI =
      0.898 to 0.988) when compared with the 677 T allele in the additive model, and
      the same results were also revealed under other genetic models. Simultaneously,
      the 1298 A allele was not associated with the breast cancer susceptibility when
      compared with the 1298 C allele (OR = 0.993, 95%CI = 0.978 to 1.009).
      Furthermore, analyses under the dominant, recessive and the allele contrast model
      yielded similar results. CONCLUSIONS: The results of this meta-analysis suggest
      that 677 C>T polymorphism in the MTHFR gene may contribute to breast cancer
      development. However, the 1298 A>C polymorphism is not significantly associated
      with increased risks of breast cancer.

PMID- 24945728
TI  - Modulation of CD6 function through interaction with Galectin-1 and -3.
AB  - CD6 is a lymphocyte glycoprotein receptor that physically associates with the
      antigen-specific receptor complex at the center of the immunological synapse,
      where it interacts with its ligand CD166/ALCAM. The present work reports the
      carbohydrate-dependent interaction of CD6 and CD166/ALCAM with Galectin-1 and -3,
      two well-known soluble mammalian lectins. Both galectins interfered with
      superantigen-induced T cell proliferation and cell adhesion phenomena mediated by
      the CD6-CD166/ALCAM pair, while CD6 expression protected cells from galectin
      induced apoptosis. The results suggest that interaction of Galectin-1 and -3 with
      CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology. 

PMID- 24945729
TI  - Mechanistic study of CMP-Neu5Ac hydrolysis by alpha2,3-sialyltransferase from
      Pasteurella dagmatis.
AB  - Bacterial sialyltransferases of the glycosyltransferase family GT-80 exhibit
      pronounced hydrolase activity toward CMP-activated sialyl donor substrates. Using
      in situ proton NMR, we show that hydrolysis of CMP-Neu5Ac by Pasteurella dagmatis
      alpha2,3-sialyltransferase (PdST) occurs with axial-to-equatorial inversion of
      the configuration at the anomeric center to release the alpha-Neu5Ac product. We
      propose a catalytic reaction through a single displacement-like mechanism where
      water replaces the sugar substrate as a sialyl group acceptor. PdST variants
      having His(284) in the active site replaced by Asn, Asp or Tyr showed up to 10(4)
      fold reduced activity, but catalyzed CMP-Neu5Ac hydrolysis with analogous
      inverting stereochemistry. The proposed catalytic role of His(284) in the PdST
      hydrolase mechanism is to facilitate the departure of the CMP leaving group. 

PMID- 24945730
TI  - Polynomial algebra reveals diverging roles of the unfolded protein response in
      endothelial cells during ischemia-reperfusion injury.
AB  - The unfolded protein response (UPR)--the endoplasmic reticulum stress response-
      is found in various pathologies including ischemia-reperfusion injury (IRI).
      However, its role during IRI is still unclear. Here, by combining two different
      bioinformatical methods--a method based on ordinary differential equations (Time
      Series Network Inference) and an algebraic method (probabilistic polynomial
      dynamical systems)--we identified the IRE1alpha-XBP1 and the ATF6 pathways as the
      main UPR effectors involved in cell's adaptation to IRI. We validated these
      findings experimentally by assessing the impact of their knock-out and knock-down
      on cell survival during IRI.

PMID- 24945731
TI  - MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by
      regulating expression of PHLPP1 and PHLPP2.
AB  - The dysregulation of microRNAs (miRNAs) is crucially implicated in the
      development of various cancers. In this study, we explored the biological role of
      miR-141 in non-small cell lung cancer (NSCLC). miR-141 expression was
      significantly up-regulated in NSCLC tissues, and its overexpression accelerated
      NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently
      identified the antagonists of PI3K/AKT signaling, PH domain leucine-rich-repeats
      protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR-141. Re
      introduction of PHLPP1 and PHLPP2 abrogated miR-141-induced proliferation of
      NSCLC cells. Together, the results of this study suggest that miR-141 and its
      targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide
      potential therapeutic targets for NSCLC treatment. 

PMID- 24945732
TI  - The intriguing complexities of mammalian gene regulation: how to link enhancers
      to regulated genes. Are we there yet?
AB  - The information encoded in genomes supports the differentiation and function of
      the more than 200 unique cell types, which exist in various mammalian species.
      The major mechanism driving cellular differentiation and specification is
      differential gene expression regulation. Cis-acting enhancers and silencers
      appear to have key roles in regulating the expression of mammalian genes.
      However, these cis-acting elements are often located very far away from the
      regulated gene. Therefore, it is hard to find all of them and link them to the
      regulated gene. An intriguing and unresolved issue of the field is to identify
      all of the enhancers of a particular gene and link these short regulatory
      sequences to the genes they regulate and thus, reliably identify gene regulatory
      enhancer networks. Recent advances in molecular biological methods coupled with
      Next-Generation Sequencing (NGS) technologies have opened up new possibilities in
      this area of genomics. In this review we summarize the technological advances,
      bioinformatics challenges and the potential molecular mechanisms allowing the
      construction of enhancer networks operating in specific cell types and/or
      activated by various signals.

PMID- 24945733
TI  - Structural modeling of Ge6.25As32.5Se61.25 using a combination of reverse Monte
      Carlo and Ab initio molecular dynamics.
AB  - Ternary glass structures are notoriously difficult to model accurately, and yet
      prevalent in several modern endeavors. Here, a novel combination of Reverse Monte
      Carlo (RMC) modeling and ab initio molecular dynamics (MD) is presented,
      rendering these complicated structures computationally tractable. A case study
      (Ge6.25As32.5Se61.25 glass) illustrates the effects of ab initio MD quench rates
      and equilibration temperatures, and the combined approach's efficacy over
      standard RMC or random insertion methods. Submelting point MD quenches achieve
      the most stable, realistic models, agreeing with both experimental and fully ab
      initio results. The simple approach of RMC followed by ab initio geometry
      optimization provides similar quality to the RMC-MD combination, for far fewer
      resources. 

PMID- 24945734
TI  - Rotational and vibrational pattern interpretation for high-resolution coherent 3D
      spectroscopy.
AB  - High-resolution coherent multidimensional spectroscopy provides an alternative to
      conventional methods for generating rotationally resolved electronic spectra of
      gas phase molecules. In addition to revealing information such as the
      relationships among peaks, it can provide clearly recognizable patterns for
      spectra that otherwise appear patternless due to rotational congestion. Despite
      this improvement, high-resolution coherent 2D spectroscopy can still exhibit
      congestion problems; expansion to the second dimension is often not sufficient to
      prevent overlapping of peaks from different patterns. A new 3D version of the
      technique that provides improved resolution and selectivity to help address cases
      with severe congestion was recently demonstrated. The experimental design and
      interpretation of data for the 3D technique are significantly more complicated
      than that for the 2D version. The purpose of this paper is to provide important
      information needed to plan, run, and interpret results from high-resolution
      coherent 3D spectroscopy experiments. 

PMID- 24945735
TI  - Reduced graphene oxide growth on 316L stainless steel for medical applications.
AB  - We report a new method for the growth of reduced graphene oxide (rGO) on the 316L
      alloy of stainless steel (SS) and its relevance for biomedical applications. We
      demonstrate that electrochemical etching increases the concentration of metallic
      species on the surface and enables the growth of rGO. This result is supported
      through a combination of Raman spectroscopy, X-ray photoelectron spectroscopy
      (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), density
      functional theory (DFT) calculations and static water contact angle measurements.
      Raman spectroscopy identifies the G and D bands for oxidized species of graphene
      at 1595 cm(-1) and 1350 cm(-1), respectively, and gives an ID/IG ratio of 1.2,
      indicating a moderate degree of oxidation. XPS shows -OH and -COOH groups in the
      rGO stoichiometry and static contact angle measurements confirm the wettability
      of rGO. SEM and AFM measurements were performed on different substrates before
      and after coronene treatment to confirm rGO growth. Cell viability studies reveal
      that these rGO coatings do not have toxic effects on mammalian cells, making this
      material suitable for biomedical and biotechnological applications. 

PMID- 24945736
TI  - Epigenetic memory takes center stage in the survival strategy of malaria
      parasites.
AB  - Malaria parasites run through a complex life cycle in the vertebrate host and
      mosquito vector. This not only requires tightly controlled mechanisms to govern
      stage-specific gene expression but also necessitates effective strategies for
      survival under changing environmental conditions. In recent years, the
      combination of different -omics approaches and targeted functional studies
      highlighted that Plasmodium falciparum blood stage parasites use heterochromatin
      based gene silencing as a unifying strategy for clonally variant expression of
      hundreds of genes. In this article, we describe the epigenetic control mechanisms
      that mediate alternative expression states of genes involved in antigenic
      variation, nutrient uptake and sexual conversion and discuss the relevance of
      this strategy for the survival and transmission of malaria parasites. 

PMID- 24945737
TI  - Serum levels of TGFbeta, IL-10, IL-17, and IL-23 cytokines in beta-thalassemia
      major patients: the impact of silymarin therapy.
AB  - Abstract Several immunological abnormalities have been characterized in beta
      thalassemia, many of which are linked to or identified with cytokines. In this
      study, we investigated the serum levels of TGF-beta, IL-10, IL-17 and IL-23 in
      beta-thalassemia major patients in comparison with healthy controls. The
      immunomodulatory effect of silymarin (a flavonoid complex obtained from Silybum
      marinum) on the serum levels of cytokines was further evaluated in thalassemia
      patients receiving silymarin (420 mg/day) and compared with patients treated with
      placebo for 6-month. Serum cytokines levels were measured by enzyme linked
      immunosorbent assay (ELISA). The results showed a significant higher
      concentration of TGF-beta and IL-23 in the patient group than control group.
      Among studied cytokines, a significant reduction in serum IL-10 levels was found
      in patients treated with silymarin when compared with IL-10 values at baseline.
      However, no significant difference was observed between baseline values of
      cytokine compared with end values in placebo group. Our data suggest the presence
      of imbalanced immune condition involving inflammation and immunosuppression in
      thalassemia patients, which could be modulated to a more effective immune
      response by silymarin.

PMID- 24945738
TI  - Pattern of Acute Retinal Necrosis in a Referral Center in Tunisia, North Africa.
AB  - PURPOSE: To describe the pattern of acute retinal necrosis (ARN) syndrome in a
      referral center in Tunisia. METHODS: Retrospective review of the charts of 12
      patients (12 eyes). RESULTS: Necrotizing retinitis involved >50% of the retina in
      33.3% of eyes. Polymerase chain reaction on aqueous humor sample identified
      herpes simplex virus-1 in 4 eyes (33.3%) and varicella zoster virus in 3 eyes
      (25%), and was negative in 5 eyes (41.7%). All patients received intravenous
      acyclovir, followed by oral antivirals. Follow-up ranged from 6 to 16 months.
      Retinal detachment (RD) occurred in 3 eyes (25%), but no patient developed
      bilateral ARN. Final visual acuity was 20/200 or worse in 7 eyes (58.3%). Delay
      in diagnosis (p = 0.015), macular involvement (p = 0.045), development of RD (p =
      0.018), and 25-50% of retinal involvement (p = 0.045) were associated with a
      worse visual outcome. CONCLUSION: ARN carries poor visual prognosis in Tunisia.

PMID- 24945739
TI  - Gelatin-based hydrogel for vascular endothelial growth factor release in
      peripheral nerve tissue engineering.
AB  - Hydrogels are promising materials in regenerative medicine applications, due to
      their hydrophilicity, biocompatibility and capacity to release drugs and growth
      factors in a controlled manner. In this study, biocompatible and biodegradable
      hydrogels based on blends of natural polymers were used in in vitro and ex vivo
      experiments as a tool for VEGF-controlled release to accelerate the nerve
      regeneration process. Among different candidates, the angiogenic factor VEGF was
      selected, since angiogenesis has been long recognized as an important and
      necessary step during tissue repair. Recent studies have pointed out that VEGF
      has a beneficial effect on motor neuron survival and Schwann cell vitality and
      proliferation. Moreover, VEGF administration can sustain and enhance the growth
      of regenerating peripheral nerve fibres. The hydrogel preparation process was
      optimized to allow functional incorporation of VEGF, while preventing its
      degradation and denaturation. VEGF release was quantified through ELISA assay,
      whereas released VEGF bioactivity was validated in human umbilical vein
      endothelial cells (HUVECs) and in a Schwann cell line (RT4-D6P2T) by assessing
      VEGFR-2 and downstream effectors Akt and Erk1/2 phosphorylation. Moreover, dorsal
      root ganglia explants cultured on VEGF-releasing hydrogels displayed increased
      neurite outgrowth, providing confirmation that released VEGF maintained its
      effect, as also confirmed in a tubulogenesis assay. In conclusion, a gelatin
      based hydrogel system for bioactive VEGF delivery was developed and characterized
      for its applicability in neural tissue engineering. Copyright (c) 2014 John Wiley
      & Sons, Ltd.

PMID- 24945740
TI  - An experimental investigation on push force and its perception during a flexible
      hose insertion task encountered in a truck assembly line.
AB  - The push force and its perception when inserting a flexible hose laterally into a
      connector were investigated. Effects of hose diameter, glove, target position and
      obstacle condition were studied. Maximum voluntary insertion forces (MVFs) under
      similar working conditions were also measured. The larger the diameter, the
      higher the force required. The peak axial forces for the hoses of 6, 12 and 16 mm
      in diameter were on average respectively 94, 122 and 184 N, representing 45%, 61%
      and 93% of MVF. Glove condition, target position and obstacle did not
      significantly affect the axial insertion force and moment, but they did affect
      effort perception. Lower effort was perceived with gloves and high and near
      position. High intra- and inter-individual variability in insertion force for a
      given hose may suggest that feedback of successful insertion was insufficient.
      The recognition of a successful insertion must be ensured to avoid unnecessary
      extra force exertion. PRACTITIONER SUMMARY: The effects of glove, hose diameter,
      target location and obstacle on push force and its perception were studied when
      inserting a flexible hose. Solutions for improving the recognition of a
      successful insertion and the hose/connector system design must be found to reduce
      force exertion to safe levels.

PMID- 24945742
TI  - Measurement of endogenous allergens in genetically modified soybeans--short
      communication.
AB  - The measurement of endogenous allergens is required by the European Commission
      (EC) as part of the compositional analysis for GM products from host plants that
      are common causes of food allergy, such as soybean (EC Implementing Regulation
      No. 503/2013). In each case, the EC Implementing Regulation indicates that
      analysis be conducted on identified allergens as specified in the Organization of
      Economic Cooperation and Development (OECD) consensus documents on compositional
      considerations for new plant varieties. This communication discusses the methods
      available to measure endogenous allergens as well as the endogenous soybean
      allergens that should be analyzed. It is suggested herein that in conjunction
      with the 2012 OECD consensus document on soybean, any list of soybean allergens
      should be based on clinically relevant data among publicly available allergen
      databases and peer-reviewed scientific publications, and the ability to measure
      the identified allergen. Based on a detailed analysis of the scientific
      literature, the following key points are recommended: (1) the acceptance of serum
      free, quantitative analytical method data as an alternative to traditional IgE
      reactivity qualitative or semi-quantitative data for evaluation of endogenous
      soybean allergen content; (2) eight of the 15 potential allergens listed in the
      OECD soybean consensus document (Gly m 3, Gly m 4, Gly m Bd28K, Gly m Bd30K, Gly
      m 5, Gly m 6, Gly m 8, and Kunitz trypsin inhibitor) have both appropriate
      supporting clinical data and sufficient sequence information to be evaluated in
      comparative endogenous soybean allergen studies; and (3) the remaining seven
      proteins (Gly m 1, Gly m 2, unknown 50kDa protein, unknown 39kDa protein, P-22
      25, lipoxygenase and lectin) lack sufficient data for clear classification as
      confirmed allergens and/or available sequence information and should not be
      currently included in the measurement of endogenous soybean allergens in the
      compositional analysis for the EU. 

PMID- 24945741
TI  - Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein
      deficiency: modulatory role of regulatory B cells.
AB  - Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein
      (WASp) are predisposed to varied autoimmunity, suggesting it has an important
      controlling role in participating cells. IL-10-producing regulatory B (Breg)
      cells are emerging as important mediators of immunosuppressive activity. In
      experimental, antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO])
      mice developed exacerbated disease associated with decreased Breg cells and
      regulatory T (Treg) cells, but increased Th17 cells in knee-draining LNs.
      Arthritic WAS KO mice showed increased serum levels of B-cell-activating factor,
      while their B cells were unresponsive in terms of B-cell-activating factor
      induced survival and IL-10 production. Adoptive transfer of WT Breg cells
      ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg
      and Th17 cells. Mice with B-cell-restricted WASp deficiency, however, did not
      develop exacerbated arthritis, despite exhibiting reduced Breg- and Treg-cell
      numbers during active disease, and Th17 cells were not increased over equivalent
      WT levels. These findings support a contributory role for defective Breg cells in
      the development of WAS-related autoimmunity, but demonstrate that functional
      competence in other regulatory populations can be compensatory. A properly
      regulated cytoskeleton is therefore important for normal Breg-cell activity and
      complementation of defects in this lineage is likely to have important
      therapeutic benefits. 

PMID- 24945743
TI  - Safety evaluation of phytase 50104 enzyme preparation (also known as VR003),
      expressed in Pseudomonas fluorescens, intended for increasing digestibility of
      phytate in monogastrics.
AB  - Phytase 50104 enzyme (also known as VR003) can be added to swine and poultry
      diets to catalyze the hydrolysis of phosphate from phytic acid, thereby
      increasing phosphorus bioavailability in these animals. This enzyme was produced
      from a Pseudomonas fluorescens (P. fluorescens) production strain and was tested
      in acute, subchronic and genotoxicity studies. Dosages of the test article
      preparation ranged from 5000MUg/plate for in vitro toxicity studies to
      2000mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo
      (NOAEL of 2000mg/kg/day) resulted in a safety margin of 5870 based on TOS and a
      conservative estimate of total poultry consumption at the highest inclusion rate.
      There was no toxicity reported for any of these studies or in the following
      additional safety studies: eye irritation, dermal irritation, and delayed
      hypersensitivity studies. A review of the public literature indicated that P.
      fluorescens fulfilled the recognized safety criteria pertinent to microbial
      production strains used in the manufacture of food/feed enzyme preparations. The
      results of the toxicity studies presented herein attest to the safety of phytase
      50104 enzyme for its intended use. 

PMID- 24945744
TI  - Signal detection for Thai traditional medicine: examination of national
      pharmacovigilance data using reporting odds ratio and reported population
      attributable risk.
AB  - Herbal containing medicine consumption has increased while the awareness of
      adverse drug reaction (ADR) was less than conventional medicine. Early detection
      of unexpected numbers of ADRs from herbal medicines' reports which are abnormal
      from the whole database needs quantification. Disproportionality analysis has
      been performed for signal detection by using reporting odds ratio (ROR) as
      measurement. The impact of having medicine as exposures in each ADR should be
      measured by using reported population attributable risks (RPAR). This study aimed
      to quantify the contribution of Thai traditional medicine (TTM) to ADR reports
      and to assess the association between TTMs and serious adverse drug reactions.
      Data were retrieved from the adverse drug reaction surveillance database, Thai
      Food and Drug Administration from 2002 to 2013. Crude and adjusted RORs for each
      drug-ADR pair and RPARs were computed. TTM contributed only 0.001% of all serious
      ADRs reported. Out of 4208 TTM-ADR pairs were examined, three had the
      statistically significant RORs, namely Andrographis paniculata and anaphylactic
      shock (ROR 2.32, 95% CI 1.03, 5.21); green traditional medicine and Stevens
      Johnson syndrome (ROR 13.04, 95% CI 5.4-31.51) and Derris scandens Benth and
      angioedema (ROR 2.71, 95% CI 1.05-6.95). Their RPARs ranged from 0.05% to 0.16%.
      We conclude that TTMs need more intensive surveillance. 

PMID- 24945746
TI  - Glow discharge plasma-assisted template removal of SBA-15 at ambient temperature
      for high surface area, high silanol density, and enhanced CO2 adsorption
      capacity.
AB  - Glow discharge plasma was successfully applied for effective removal of the
      organic template P-123 from SBA-15 ordered mesoporous silica at near-room
      temperature (below 50  degrees C) and in a short operation time (2 h). The as
      made SBA-15 treated with glow discharge exhibited a larger surface area of 1025
      m(2) g(-1) with larger pores and microspore volume as compared with that of
      conventional calcination (550  degrees C and 5 h, 827 m(2) g(-1)). In addition to
      less structural shrinkage, the plasma-prepared SBA-15 showed significantly
      increased silanol density from 5.4 to 6.6-7.6 mmol g(-1), which led directly to
      higher amine loading from 1.8 to 3.0 mmol g(-1). Consequently, the plasma-treated
      sample showed 77% more CO2 capacity and 60% higher CO2/N2 selectivity than the
      conventionally treated sample at 0.15 bar and 25  degrees C. The advantage of
      using glow discharge plasma for low-temperature template removal for achieving
      enhanced performance for CO2 adsorption is clearly demonstrated. 

PMID- 24945747
TI  - Multiplexed microRNA detection using lanthanide-labeled DNA probes and laser
      ablation inductively coupled plasma mass spectrometry.
AB  - In the past decade, microRNAs (miRNAs) have drawn increasing attention due to
      their role in regulation of gene expression. Especially, their potential as
      biomarkers in disease diagnostics has motivated miRNA research, including the
      development of simple, accurate, and sensitive detection methods. The narrow size
      range of miRNAs (20-24 nucleotides) combined with the chemical properties of
      conventional reporter tags has hampered the development of multiplexed miRNA
      assays. In this study, we have used lanthanide-labeled DNA probes for the
      detection of miRNAs on membranes using laser ablation inductively coupled plasma
      mass spectrometry (LA-ICPMS). Three miRNAs from Arabidopsis thaliana were
      analyzed simultaneously with high specificity, and the sensitivity of the method
      was comparable to radioactive detection (low femtomol range). The perspective of
      the developed method is highly multiplexed and quantitative miRNA analysis with
      high specificity and sensitivity. 

PMID- 24945748
TI  - Physical properties of EuPd2As2 single crystals.
AB  - The physical properties of self-flux grown EuPd2As2 single crystals have been
      investigated by means of magnetization M, magnetic susceptibility chi, specific
      heat Cp, and electrical resistivity rho measurements versus temperature T and
      magnetic field H. The crystal structure was determined using powder x-ray
      diffraction measurements, which confirmed the ThCr2Si2-type body-centered
      tetragonal structure (space group I4/mmm) reported previously. The rho(T) data
      indicate that EuPd2As2 is metallic. The chi(T) data indicate that the Eu(+2)
      moments have spin S = 7/2 with g = 2. Long-range antiferromagnetic (AFM) ordering
      is apparent from the chi(T), Cp(T), and rho(T) measurements. For H?c the chi(T)
      indicates two transitions at TN1 = 11.0 K and TN2 = 5.5 K, whereas for H?c only
      one transition is observed at TN1 = 11.0 K. Between TN1 and TN2 the anisotropic
      chi(T) data suggest a planar noncollinear AFM structure, whereas at T < TN2 the
      chi(T) and M(H, T) data suggest a spin reorientation transition in which equal
      numbers of spins cant in opposite directions out of the ab plane. We estimate the
      critical field at 2 K at which all Eu moments become aligned with the field to be
      about 22 T. An upturn in rho at T < TN1 suggests superzone energy gap formation
      below TN1. This behavior of rho(T < TN1) is not sensitive to applied magnetic
      fields up to H = 12 T.

PMID- 24945745
TI  - Long-distance communication between laryngeal carcinoma cells.
AB  - Tunneling nanotubes and epithelial bridges are recently discovered new forms of
      intercellular communication between remote cells allowing their electrical
      synchronization, transfer of second messengers and even membrane vesicles and
      organelles. In the present study, we demonstrate for the first time in primary
      cell cultures prepared from human laryngeal squamous cell carcinoma (LSCC)
      samples that these cells communicate with each other over long distances (up to 1
      mm) through membranous tunneling tubes (TTs), which can be open-ended or contain
      functional gap junctions formed of connexin 43. We found two types of TTs,
      containing F-actin alone or F-actin and alpha-tubulin. In the LSCC cell culture,
      we identified 5 modes of TT formation and performed quantitative assessment of
      their electrical properties and permeability to fluorescent dyes of different
      molecular weight and charge. We show that TTs, containing F-actin and alpha
      tubulin, transport mitochondria and accommodate small DAPI-positive vesicles
      suggesting possible transfer of genetic material through TTs. We confirmed this
      possibility by demonstrating that even TTs, containing gap junctions, were
      capable of transmitting double-stranded small interfering RNA. To support the
      idea that the phenomenon of TTs is not only typical of cell cultures, we have
      examined microsections of samples obtained from human LSCC tissues and identified
      intercellular structures similar to those found in the primary LSCC cell culture.

PMID- 24945749
TI  - An assessment of pain management among patients presenting to emergency medical
      services after suffering a fall.
AB  - INTRODUCTION: Emergency Medical Services (EMS) professionals frequently care for
      patients experiencing acute pain. Analgesics are critical in patient comfort and
      satisfaction levels during the treatment of acute pain. The objective of this
      study was to assess the frequency of pain management in patients suffering a
      fall, the documented pain score, and the location of their injuries. It was
      hypothesized that the frequency of analgesia administration was low and would be
      associated with injury location. METHODS: This was a retrospective review of
      patients presenting with a complaint of an injury from a fall transported by a
      single municipal EMS system. Administration of analgesia was the primary outcome
      variable, with pain severity, injury location, age, gender, race, and distance of
      fall the independent variables of interest. Pain severity was assessed using a 0
      10 scale. Injury location was defined as head/neck, extremities, back, and hip.
      Patients were deemed ineligible for analgesia, according to local protocol, if
      they reported chest or abdominal pain, or were hemodynamically unstable as
      determined by an assessment of pulse and blood pressure. RESULTS: There were
      1,200 patients who were classified as having injuries suffered from a fall, with
      76 (6.3%) ineligible for analgesia. Ninety-two (8.2%) patients received
      analgesia, and they had a mean recorded pain score of 9.1 (95% CI, 8.7-9.5),
      which was higher than those who did not receive analgesia (5.8; 95% CI, 5.5-6.2).
      Analgesia administration was associated with injury location; patients
      experiencing an extremity injury (OR = 13.23; 95% CI, 5.58-31.36; P < .001) or
      hip injury (OR = 11.65; 95% CI, 4.64-29.24; P < .001) had increased odds of
      analgesia administration compared to those with head/neck injury. The odds of
      analgesia administration were decreased for black patients (OR = 0.19; 95% CI,
      0.08-0.44; P < .001) when compared to white patients. CONCLUSION: Analgesia
      administration was provided to 10% of eligible patients, and was associated with
      injury location. Of concern was the number of patients who suffered a fall and
      did not receive a documented pain score. The results from this study indicated a
      need for education relating to pain management in patients suffering a fall.

PMID- 24945750
TI  - A case for competency-based anaesthesiology training with entrustable
      professional activities: an agenda for development and research.
AB  - Competency frameworks are based on what are considered to be the general
      essential qualities of a doctor. Competencies, being behavioural descriptors,
      need a strong link to clinical practice to allow trainers to observe and then use
      them in assessing trainees' performance. The emerging concept of entrustable
      professional activities (EPAs) may serve as such a link. An EPA is a description
      of an essential clinical task that frames competencies in the context of clinical
      practice. A full set of EPAs defines a specialty and constitutes the curriculum
      of specialty training. After observation of satisfactory performance on an EPA,
      the resident should be permitted to perform that activity without direct
      supervision. The terms of this should allow a trainer to provide justification
      for this decision. This makes graded assumption of responsibilities possible. We
      describe the potential benefits of working with EPAs in anaesthesiology training
      and set an agenda for curriculum development and research in this area. 

PMID- 24945751
TI  - Transmission and persistence of Ceratonova shasta genotypes in Chinook salmon.
AB  - Ceratonova shasta is a myxozoan parasite of salmon and trout transmitted by
      waterborne actinospores. Based on DNA sequence data and host specificity, 4
      distinct parasite genotypes are recognized. Genotypes I and II are common in the
      lower reaches of the Klamath River, Oregon-California, but only infection by
      genotype I causes mortality in Chinook salmon. We conducted sentinel fish
      exposures and determined genotype composition in river water during exposure, and
      in fish gills, intestine, and tank water post-exposure to determine whether: (1)
      transmission of parasites having different genotypes is host-specific and (2) all
      transmitted genotypes persist in the host through to release as waterborne
      stages. Initial parasite transmission to the fish host appears indiscriminant,
      since we detected both genotypes I and II in 83.6% of the fish gills sampled.
      However, only genotype I was detected in fish that succumbed to infection, while
      both genotypes persisted in fish that survived. Persistence was likely dependent
      on exposure dose, initial infection type (mixed or single) and infection outcome
      (mortality or survival). The transmission of both genotypes to a majority of
      Chinook salmon and the persistence of multiple genotypes raises questions about
      how infection with mixed genotypes could result in within-host interactions that
      affect disease severity.

PMID- 24945752
TI  - Pendant ancillary ligand switches off auto-oxidation of group 13 metal alkyl
      compounds bearing non-bulky alkyl groups.
AB  - The reaction of 3,5-di-2-pyridyl-1,2,4-triazole with excess Al(CH3)3 and Ga(CH3)3
      afforded (3,5-di-2-pyridyl-1,2,4-triazolate)Al(CH3)2*3Al(CH3)3 (1) and (3,5-di-2
      pyridyl-1,2,4-triazolate) Ga(CH3)2*3Ga(CH3)3 (2) respectively. 1 and 2 reacted
      with oxygen gas to produce (CH3)2M(u-3,5-di-2-pyridyl-1,2,4-triazolate)(u
      OCH3)M(CH3)2 (M = Al, 3; M = Ga, 4). 3 and 4 contain the non-bulky
      dimethylalumino moiety, yet they are indefinitely stable in the presence of
      oxygen gas. This increased stability towards oxygen is due to ancillary 2-pyridyl
      groups bonding to the metal centers producing a pseudo-trigonal pyramidal Al and
      Ga environments. This environment blocks oxygen from further inserting into the M
      C bond. The Al-N(pyridine) and Ga-N(pyridine) bonds reported herein are extremely
      elongated yet inactive towards dissociation due to the chelate effect. 

PMID- 24945753
TI  - Wightianines A-E, dihydro-beta-agarofuran sesquiterpenes from Parnassia
      wightiana, and their antifungal and insecticidal activities.
AB  - Five new sesquiterpene polyol esters with a dihydro-beta-agarofuran skeleton,
      designated as wightianines A-E (1-5), besides two known compounds, were isolated
      from the methanolic extract of the whole plant of the traditional herbal medicine
      Parnassia wightiana Wall. The structures of the isolated compounds were
      elucidated on the basis of spectroscopic analyses, including two-dimensional
      nuclear magnetic resonance techniques (correlation spectroscopy, heteronuclear
      multiple-quantum coherence, nuclear Overhauser effect spectrometry, and
      heteronuclear multiple-bond correlation) and electronic circular dichroism
      studies. The antifungal and insecticidal activities of five compounds were
      evaluated against several plant pathogenic fungi and armyworm larvae (Mythimna
      separata Walker). Among the test metabolites, compounds 2 and 7 both exhibited
      potent antifungal activity against the phytopathogenic fungus Cytospora sp. with
      minimum inhibitory concentration values of 0.78 MUg/mL, which are equal to the
      two positive controls, hymexazol and carbendazim. However, no insecticidal
      activity of the test compounds was observed in the present study. Compounds 2 and
      7 could be promising leads for developing new fungicides against agriculturally
      important fungus Cytospora sp. 

PMID- 24945756
TI  - Ex vivo blister induction: a more sensitive technique for immunofluorescence
      mapping studies in inherited epidermolysis bullosa.

PMID- 24945754
TI  - High levels of SOX5 decrease proliferative capacity of human B cells, but permit
      plasmablast differentiation.
AB  - Currently very little is known about the differential expression and function of
      the transcription factor SOX5 during B cell maturation. We identified two new
      splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and
      a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during
      late stages of B-cell differentiation, including atypical memory B cells,
      activated CD21low B cells and germinal center B cells of tonsils. In tonsillar
      sections SOX5 expression was predominantly polarized to centrocytes within the
      light zone. After in vitro stimulation, SOX5 expression was down-regulated during
      proliferation while high expression levels were permissible for plasmablast
      differentiation. Overexpression of L-SOX5F in human primary B lymphocytes
      resulted in reduced proliferation, less survival of CD138neg B cells, but
      comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus,
      our findings describe for the first time a functional role of SOX5 during late B
      cell development reducing the proliferative capacity and thus potentially
      affecting the differentiation of B cells during the germinal center response. 

PMID- 24945755
TI  - Cloning and characterization of a unique cytotoxic protein parasporin-5 produced
      by Bacillus thuringiensis A1100 strain.
AB  - Parasporin is the cytocidal protein present in the parasporal inclusion of the
      non-insecticidal Bacillus thuringiensis strains, which has no hemolytic activity
      but has cytocidal activities, preferentially killing cancer cells. In this study,
      we characterized a cytocidal protein that belongs to this category, which was
      designated parasporin-5 (PS5). PS5 was purified from B. thuringiensis serovar
      tohokuensis strain A1100 based on its cytocidal activity against human leukemic T
      cells (MOLT-4). The 50% effective concentration (EC50) of PS5 to MOLT-4 cells was
      approximately 0.075 MUg/mL. PS5 was expressed as a 33.8-kDa inactive precursor
      protein and exhibited cytocidal activity only when degraded by protease at the C
      terminal into smaller molecules of 29.8 kDa. Although PS5 showed no significant
      homology with other known parasporins, a Position Specific Iterative-Basic Local
      Alignment Search Tool (PSI-BLAST) search revealed that the protein showed slight
      homology to, not only some B. thuringiensis Cry toxins, but also to aerolysin
      type beta-pore-forming toxins (beta-PFTs). The recombinant PS5 protein could be
      obtained as an active protein only when it was expressed in a precursor followed
      by processing with proteinase K. The cytotoxic activities of the protein against
      various mammalian cell lines were evaluated. PS5 showed strong cytocidal activity
      to seven of 18 mammalian cell lines tested, and low to no cytotoxicity to the
      others.

PMID- 24945757
TI  - Postirradiation Pseudosclerodermatous Panniculitis of the Leg: Report of a Case
      and Review of the Literature.
AB  - Postirradiation pseudosclerodermatous panniculitis presents as an erythematous
      indurated plaque, on a previously irradiated area. Histopathologically, thick and
      sclerotic septa and inflammatory infiltrate with foamy histiocytes and
      adiponecrosis are seen. To date, 12 cases have been reported worldwide. Hereby,
      we report the case of a 68-year-old woman who developed an indurated painful
      erythematous plaque on her right leg after radiotherapy for a soft tissue
      sarcoma, with a septal panniculitis and lobular adiponecrosis on
      histopathological examination. This is the 13th case reported and the second of
      extrathoracic location. 

PMID- 24945758
TI  - The vagus nerve, recurrent laryngeal nerve, and external branch of the superior
      laryngeal nerve have unique latencies allowing for intraoperative documentation
      of intact neural function during thyroid surgery.
AB  - OBJECTIVES/HYPOTHESIS: To define normative amplitude and latency of vagus,
      recurrent laryngeal nerve (RLN), and external branch of superior laryngeal nerve
      (EBSLN) and to apply them to postoperative neural function documentation. To our
      knowledge, this is the first study to report electrophysiologic characteristics
      of all three nerves in a consecutive patient series. STUDY DESIGN: Prospective.
      METHODS: Quantitative analysis of evoked waveform data was performed on both
      sides in consecutive patients undergoing thyroid surgery by a single surgeon.
      Mean values, standard error of mean, and standard deviation were calculated for
      latency (in milliseconds) and amplitude (in microvolts) of the vagus nerves, RLN,
      and EBSLN. Pre- and postoperative vocal cord function was normal in all patients.
      RESULTS: Normative latency analysis showed mean right and left vagal latency of
      5.47 ms (+/-0.73) and 8.14 ms (+/-0.86), respectively (P < .0001). Pooled RLN
      latency was 3.96 ms (+/-0.69), and pooled EBSLN latency was 3.56 ms (+/-0.49),
      both significantly shorter than vagal latencies (P < .0001). There was no
      association between amplitude and latency parameters and tumor-size (> or <5 cm),
      body mass index (> or <25), age (> or <50 years), gender, or degree of neural
      dissection. CONCLUSIONS: The unique right vagus, left vagus, and RLN latencies
      are characteristic of the individual nerves and allow identification (through the
      characteristic waveform latency) of an intact left or right vagus/RLN system.
      Timed recording of vagal waveform after thyroid lobectomy consequently documents
      intact ipsilateral vagal-RLN neural circuit and may be placed into the medical
      record as electrophysiologic documentation of existence of postresection complete
      neural integrity. LEVEL OF EVIDENCE: 4.

PMID- 24945759
TI  - Multimodal injury risk analysis of road users at signalized and non-signalized
      intersections.
AB  - This paper proposes a multimodal approach to study safety at intersections by
      simultaneously analysing the safety and flow outcomes for both motorized and non
      motorized traffic. This study uses an extensive inventory of signalized and non
      signalized intersections on the island of Montreal, Quebec, Canada, containing
      disaggregate motor-vehicle, cyclist and pedestrian flows, injury data, geometric
      design, traffic control and built environment characteristics in the vicinity of
      each intersection. Bayesian multivariate Poisson models are used to analyze the
      injury and traffic flow outcomes and to develop safety performance functions for
      each mode at both facilities. After model calibration, contributing injury
      frequency factors are identified. Injury frequency and injury risk measures are
      then generated to carry out a comparative study to identify which mode is at
      greatest risk at intersections in Montreal. Among other results, this study
      identified the significant effect that motor-vehicle traffic imposes on cyclist
      and pedestrian injury occurrence. Motor-vehicle traffic is the main risk
      determinant for all injury and intersection types. This highlights the need for
      safety improvements for cyclists and pedestrians who are, on average, at 14 and12
      times greater risk than motorists, respectively, at signalized intersections.
      Aside from exposure measures, this work also identifies some geometric design and
      built environment characteristics affecting injury occurrence for cyclists,
      pedestrians and motor-vehicle occupants. 

PMID- 24945760
TI  - Tau propagation, different tau phenotypes, and prion-like properties of tau.
AB  - Sanders et al. (2014) demonstrate in this issue of Neuron that the natively
      unfolded protein tau can propagate indefinitely in distinct stable strains,
      therefore supporting the general idea that tau has prion-like properties, with
      implications for Alzheimer's disease and other tauopathies.

PMID- 24945761
TI  - For better or worse: reward comparison by the ventromedial prefrontal cortex.
AB  - In this issue of Neuron, Strait et al. (2014) studied how neurons in the monkey
      ventromedial prefrontal cortex encode value-based decisions. Neurons were
      commonly influenced by reward magnitude and probability, showed anticorrelation
      for better and worse options, and covaried with choice independent of value.

PMID- 24945762
TI  - Bringing the dynamics of movement under control.
AB  - The mechanisms underlying the dynamics of movement-related neural activity are
      not known. In this issue of Neuron, Hennequin et al. (2014) show that a recurrent
      network whose spontaneous activity is stabilized by learning reproduces many
      aspects of preparatory and movement-related activity.

PMID- 24945763
TI  - A tale of two sexes.
AB  - This year marks the first time that the largest Neuroscience societies in the
      U.S. and Europe are led by females. Here we discuss the challenges that women
      face in moving through the ranks of academia and propose ways to increase women's
      representation in the field. 

PMID- 24945764
TI  - Basic neuroscience research with nonhuman primates: a small but indispensable
      component of biomedical research.
AB  - Research with nonhuman primates represents a small component of neuroscience with
      far-reaching relevance that is irreplaceable for essential insights into
      cognitive functions, brain disease, and therapy. Transparency and widespread
      information about this research and its importance is central to ensure the
      support of politicians and the general public. 

PMID- 24945765
TI  - The cost of brain diseases: a burden or a challenge?
AB  - Brain diseases represent a considerable social and economic burden in Europe.
      With yearly costs of about 800 billion euros and an estimated 179 million people
      afflicted in 2010, brain diseases are an unquestionable emergency and a grand
      challenge for neuroscientists.

PMID- 24945766
TI  - Megascience efforts and the brain.
AB  - Several recent megascale neuroscience efforts in the U.S. and Europe are
      concerned with developing infrastructure for tools, modeling, or
      neuroinformatics. It may seem surprising that they are not instead focused
      directly on gaining fundamental new insights into brain function.

PMID- 24945767
TI  - The Human Brain Project: social and ethical challenges.
AB  - Focusing on the Human Brain Project, I discuss some social and ethical challenges
      raised by such programs of research: the possibility of a unified knowledge of
      "the brain," balancing privacy and the public good, dilemmas of "dual use," brain
      computer interfaces, and "responsible research and innovation" in governance of
      emerging technologies. 

PMID- 24945768
TI  - Network plasticity in adaptive filtering and behavioral habituation.
AB  - The ability of organisms to seamlessly ignore familiar, inconsequential stimuli
      improves their selective attention and response to salient features of the
      environment. Here, I propose that this fundamental but unexplained phenomenon
      substantially derives from the ability of any pattern of neural excitation to
      create an enhanced inhibitory (or "negative") image of itself through target
      specific scaling of inhibitory inputs onto active excitatory neurons. Familiar
      stimuli encounter strong negative images and are therefore less likely to be
      transmitted to higher brain centers. Integrating historical and recent
      observations, the negative-image model described here provides a mechanistic
      framework for understanding habituation, which is connected to ideas on dynamic
      predictive coding. In addition, it suggests insights for understanding autism
      spectrum disorders.

PMID- 24945769
TI  - Overt responses during covert orienting.
AB  - A distributed network of cortical and subcortical brain areas controls our
      oculomotor behavior. This network includes the superior colliculus (SC), which
      coordinates an ancient visual grasp reflex via outputs that ramify widely within
      the brainstem and spinal cord, accessing saccadic and other premotor and
      autonomic circuits. In this Review, we discuss recent results correlating
      subliminal SC activity in the absence of saccades with diverse components of the
      visual grasp reflex, including neck and limb muscle recruitment, pupil dilation,
      and microsaccade propensity. Such subtle manifestations of covert orienting are
      accessible in the motor periphery and may provide the next generation of
      oculomotor biomarkers in health and disease.

PMID- 24945770
TI  - Off-target effect of doublecortin family shRNA on neuronal migration associated
      with endogenous microRNA dysregulation.
AB  - Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing
      brain is a powerful technique to study genetic function; however, discrepancies
      between knockdown and knockout murine phenotypes have left unanswered questions.
      For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical
      neuronal migration phenotype. Here we report that in utero electroporation of
      shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx
      knockouts akin to the effect in wild-type mice, suggesting shRNA-mediated off
      target toxicity. This effect was not limited to Dcx, as it was observed in Dclk1
      knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence
      dependent but not sequence-specific effect. Profiling RNAs from electroporated
      cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or
      Dicer recapitulated the migration defect. The results suggest that shRNA-mediated
      knockdown can produce untoward migration effects by altering endogenous miRNA
      pathways.

PMID- 24945771
TI  - Norepinephrine controls astroglial responsiveness to local circuit activity.
AB  - Astrocytes perform crucial supportive functions, including neurotransmitter
      clearance, ion buffering, and metabolite delivery. They can also influence blood
      flow and neuronal activity by releasing gliotransmitters in response to
      intracellular Ca(2+) transients. However, little is known about how astrocytes
      are engaged during different behaviors in vivo. Here we demonstrate that
      norepinephrine primes astrocytes to detect changes in cortical network activity.
      We show in mice that locomotion triggers simultaneous activation of astrocyte
      networks in multiple brain regions. This global stimulation of astrocytes was
      inhibited by alpha-adrenoceptor antagonists and abolished by depletion of
      norepinephrine from the brain. Although astrocytes in visual cortex of awake mice
      were rarely engaged when neurons were activated by light stimulation alone,
      pairing norepinephrine release with light stimulation markedly enhanced astrocyte
      Ca(2+) signaling. Our findings indicate that norepinephrine shifts the gain of
      astrocyte networks according to behavioral state, enabling astrocytes to respond
      to local changes in neuronal activity.

PMID- 24945772
TI  - Balanced interhemispheric cortical activity is required for correct targeting of
      the corpus callosum.
AB  - Bilateral integration of sensory and associative brain processing is achieved by
      precise connections between homologous regions in the two hemispheres via the
      corpus callosum. These connections form postnatally, and unilateral deprivation
      of sensory or spontaneous cortical activity during a critical period severely
      disrupts callosal wiring. However, little is known about how this early activity
      affects precise circuit formation. Here, using in utero electroporation of
      reporter genes, optogenetic constructs, and direct disruption of activity in
      callosal neurons combined with whisker ablations, we show that balanced
      interhemispheric activity, and not simply intact cortical activity in either
      hemisphere, is required for functional callosal targeting. Moreover, bilateral
      ablation of whiskers in symmetric or asymmetric configurations shows that
      spatially symmetric interhemispheric activity is required for appropriate
      callosal targeting. Our findings reveal a principle governing axon targeting,
      where spatially balanced activity between regions is required to establish their
      appropriate connectivity. 

PMID- 24945773
TI  - Triad3A regulates synaptic strength by ubiquitination of Arc.
AB  - Activity-dependent gene transcription and protein synthesis underlie many forms
      of learning-related synaptic plasticity. At excitatory glutamatergic synapses,
      the immediate early gene product Arc/Arg3.1 couples synaptic activity to
      postsynaptic endocytosis of AMPA-type glutamate receptors. Although the
      mechanisms for Arc induction have been described, little is known regarding the
      molecular machinery that terminates Arc function. Here, we demonstrate that the
      RING domain ubiquitin ligase Triad3A/RNF216 ubiquitinates Arc, resulting in its
      rapid proteasomal degradation. Triad3A associates with Arc, localizes to clathrin
      coated pits, and is associated with endocytic sites in dendrites and spines. In
      the absence of Triad3A, Arc accumulates, leading to the loss of surface AMPA
      receptors. Furthermore, loss of Triad3A mimics and occludes Arc-dependent forms
      of synaptic plasticity. Thus, degradation of Arc by clathrin-localized Triad3A
      regulates the availability of synaptic AMPA receptors and temporally tunes Arc
      mediated plasticity at glutamatergic synapses.

PMID- 24945774
TI  - Reduced cognition in Syngap1 mutants is caused by isolated damage within
      developing forebrain excitatory neurons.
AB  - Syngap1 haploinsufficiency is a common cause of sporadic intellectual disability.
      Syngap1 mutations disrupt developing pyramidal neurons, although it remains
      unclear if this process contributes to cognitive abnormalities. Here, we found
      that haploinsufficiency restricted to forebrain glutamatergic neurons was
      sufficient to disrupt cognition and removing mutations from this population
      prevented cognitive abnormalities. In contrast, manipulating Syngap1 function in
      GABAergic neurons had no effect on cognition, excitability, or neurotransmission,
      highlighting the specificity of Syngap1 mutations within forebrain excitatory
      neurons. Interestingly, cognitive abnormalities were reliably predicted by the
      emergence of enhanced excitatory synaptic function in mature superficial cortical
      pyramidal cells, which was a neurophysiological disruption caused by Syngap1
      dysfunction in developing, but not adult, forebrain neurons. We conclude that
      reduced cognition in Syngap1 mutants is caused by isolated damage to developing
      forebrain glutamatergic neurons. This damage triggers secondary disruptions to
      synaptic homeostasis in mature cortical pyramidal cells, which perpetuates brain
      dysfunction into adulthood.

PMID- 24945775
TI  - beta-Amyloid inhibits E-S potentiation through suppression of cannabinoid
      receptor 1-dependent synaptic disinhibition.
AB  - It has been widely reported that beta-amyloid peptide (Abeta) blocks long-term
      potentiation (LTP) of hippocampal synapses. Here, we show evidence that Abeta
      more potently blocks the potentiation of excitatory postsynaptic potential (EPSP)
      spike coupling (E-S potentiation). This occurs, not by direct effect on
      excitatory synapses or postsynaptic neurons, but rather through an indirect
      mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition.
      During high-frequency (tetanic) stimulation, somatic synaptic inhibition is
      suppressed by endocannabinoids. We find that Abeta prevents this endocannabinoid
      mediated disinhibition, thus leaving synaptic inhibition more intact during
      tetanic stimulation. This intact inhibition opposes the normal depolarization of
      hippocampal pyramidal neurons that occurs during tetanus, thus opposing the
      induction of synaptic plasticity. Thus, a pathway through which Abeta can act to
      modulate neural activity is identified, relevant to learning and memory and how
      it may mediate aspects of the cognitive decline seen in Alzheimer's disease.

PMID- 24945776
TI  - Ongoing network state controls the length of sleep spindles via inhibitory
      activity.
AB  - Sleep spindles are major transient oscillations of the mammalian brain. Spindles
      are generated in the thalamus; however, what determines their duration is
      presently unclear. Here, we measured somatic activity of excitatory
      thalamocortical (TC) cells together with axonal activity of reciprocally coupled
      inhibitory reticular thalamic cells (nRTs) and quantified cycle-by-cycle
      alterations in their firing in vivo. We found that spindles with different
      durations were paralleled by distinct nRT activity, and nRT firing sharply
      dropped before the termination of all spindles. Both initial nRT and TC activity
      was correlated with spindle length, but nRT correlation was more robust. Analysis
      of spindles evoked by optogenetic activation of nRT showed that spindle
      probability, but not spindle length, was determined by the strength of the light
      stimulus. Our data indicate that during natural sleep a dynamically fluctuating
      thalamocortical network controls the duration of sleep spindles via the major
      inhibitory element of the circuits, the nRT.

PMID- 24945777
TI  - Closed-loop decoder adaptation shapes neural plasticity for skillful
      neuroprosthetic control.
AB  - Neuroplasticity may play a critical role in developing robust, naturally
      controlled neuroprostheses. This learning, however, is sensitive to system
      changes such as the neural activity used for control. The ultimate utility of
      neuroplasticity in real-world neuroprostheses is thus unclear. Adaptive decoding
      methods hold promise for improving neuroprosthetic performance in nonstationary
      systems. Here, we explore the use of decoder adaptation to shape neuroplasticity
      in two scenarios relevant for real-world neuroprostheses: nonstationary
      recordings of neural activity and changes in control context. Nonhuman primates
      learned to control a cursor to perform a reaching task using semistationary
      neural activity in two contexts: with and without simultaneous arm movements.
      Decoder adaptation was used to improve initial performance and compensate for
      changes in neural recordings. We show that beneficial neuroplasticity can occur
      alongside decoder adaptation, yielding performance improvements, skill retention,
      and resistance to interference from native motor networks. These results
      highlight the utility of neuroplasticity for real-world neuroprostheses.

PMID- 24945778
TI  - Optimal control of transient dynamics in balanced networks supports generation of
      complex movements.
AB  - Populations of neurons in motor cortex engage in complex transient dynamics of
      large amplitude during the execution of limb movements. Traditional network
      models with stochastically assigned synapses cannot reproduce this behavior. Here
      we introduce a class of cortical architectures with strong and random excitatory
      recurrence that is stabilized by intricate, fine-tuned inhibition, optimized from
      a control theory perspective. Such networks transiently amplify specific activity
      states and can be used to reliably execute multidimensional movement patterns.
      Similar to the experimental observations, these transients must be preceded by a
      steady-state initialization phase from which the network relaxes back into the
      background state by way of complex internal dynamics. In our networks, excitation
      and inhibition are as tightly balanced as recently reported in experiments across
      several brain areas, suggesting inhibitory control of complex excitatory
      recurrence as a generic organizational principle in cortex.

PMID- 24945779
TI  - Static and Dynamic Disorder in Bacterial Light-Harvesting Complex LH2: A 2DES
      Simulation Study.
AB  - Two-dimensional coherent electronic spectroscopy (2DES) is a powerful technique
      in distinguishing homogeneous and inhomogeneous broadening contributions to the
      spectral line shapes of molecular transitions induced by environment
      fluctuations. Using an excitonic model of a double-ring LH2 aggregate, we perform
      simulations of its 2DES spectra and find that the model of a harmonic environment
      cannot provide a consistent set of parameters for two temperatures: 77 K and room
      temperature. This indicates the highly anharmonic nature of protein fluctuations
      for the pigments of the B850 ring. However, the fluctuations of B800 ring
      pigments can be assumed as harmonic in this temperature range.

PMID- 24945781
TI  - Voice therapy: From the past to the present from a phoniatrician's perspective
      (Voice of Experience Keynote, PEVOC 2013, Prague).
AB  - The roots of voice therapy can be traced back to the professional use of the
      voice in antiquity. During the Baroque period, aspects of the singers' voice came
      to the fore, and in the beginning of the twentieth century, physiologic and
      medical perspectives concentrating on the peripheral areas of phonation were
      introduced. In parallel, holistic approaches stressed psychological and
      behavioral conditions. A vast amount of specific methods and strategies has been
      developed, but so far there has been no clear evidence revealing which of the
      approaches provides the best efficacy. According to the experience of the author,
      rather than the method itself, it is the clinician using the methods who makes
      the difference. The general guide-line for the choice of an appropriate treatment
      should be the Hippocratic imperative: primum nil nocere--first do no harm.

PMID- 24945780
TI  - The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2
      genotyping.
AB  - BACKGROUND/OBJECTIVES: The polymorphic hepatic enzyme CYP2C19 catalyzes the
      metabolism of clinically important drugs such as clopidogrel, proton-pump
      inhibitors, and others and clinical pharmacogenetic testing for clopidogrel is
      increasingly common. The CYP2C19*10 single-nucleotide polymorphism (SNP) is
      located 1 bp upstream the CYP2C19*2 SNP. Despite the low frequency of the
      CYP2C19*10 allele, its impact on metabolism of CYP2C19 substrates and CYP2C19*2
      genotyping makes it an important SNP to consider for pharmacogenetic testing of
      CYP2C19. However, the effect of the CYP2C19*10 allele on clopidogrel metabolism
      has not been explored to date. METHODS: We measured the enzymatic activity of the
      CYP2C19.10 protein against clopidogrel. DNA samples from two clinical studies
      were genotyped for CYP2C19*2 and *10 by pyrosequencing genotyping method.
      RESULTS: The catalytic activity of CYP2C19.10 in the biotransformation of
      clopidogrel and 2-oxo-clopidogrel was significantly decreased relative to the
      wild-type CYP2C19.1B. We also reported that the CYP2C19*10 SNP interferes with
      the CYP2C19*2 TaqMan genotyping assay, resulting in miscalling of CYP2C19*10/*2
      as CYP2C19*2/*2. CONCLUSIONS: Our data provide evidence that CYP2C19.10 variant
      partially metabolizes clopidogrel and 2-oxo-clopidogrel, and the presence of
      CYP2C19*10 allele affects the CY2C19*2 TaqMan genotyping assay and results in
      misclassification of CYP2C19*10/*2 as CYP2C19*2/*2.

PMID- 24945782
TI  - Mesoscopic metal nanoparticles doubly functionalized with natural and engineered
      lipidic dispersants for therapeutics.
AB  - Surface engineering of mesoscopic metal nanoparticles to increase
      biocompatibility and cell interaction is important for improvement of their
      therapeutic properties. Here, we describe a strategy to stabilize mesoscopic
      metal nanoparticles and to enhance their cell interaction by stepwise addition of
      (Z)-9-octadecenoate (oleate) and a cell-penetrating peptide-fused high-density
      lipoprotein (cpHDL). Oleate replaces a cytotoxic dispersant on the surface of
      gold nanorods (AuNRs), which enables subsequent cpHDL binding without causing
      aggregation. Notably, these two lipidic dispersants are probably intercalated on
      the surface. This procedure was also used to stabilize 20 nm spherical gold
      nanoparticles and 40 nm aggregates of 10 nm magnetite nanoparticles. cpHDL-bound
      AuNRs were internalized greater than 80 times more efficiently than poly(ethylene
      glycol)-conjugated AuNRs and were able to elicit cancer cell photoablation. 

PMID- 24945783
TI  - Intrathecal baclofen pump implantation in prone position for a cerebral palsy
      patient with severe scoliosis: a case report.
AB  - BACKGROUND AND OBJECTIVE: Intrathecal baclofen (ITB) pump implantation for
      cerebral palsy (CP) patients is usually performed in the lateral position;
      however, it might be difficult for some patients with severe deformity to take a
      lateral position during surgery. METHOD: We report a case of ITB pump
      implantation in the prone position for a CP patient who exhibited uncontrollable
      opisthotonus with severe scoliosis. RESULT: ITB therapy effectively controlled
      her opisthotonus. CONCLUSION: Our findings suggest that ITB therapy may be useful
      for CP patients with uncontrollable spasticity, dystonia, or opisthotonus who are
      not able to take a lateral position for pump implantation due to deformities of
      their extremities and spine.

PMID- 24945784
TI  - Fractal dimension of sparkles in automotive metallic coatings by multispectral
      imaging measurements.
AB  - Sparkle in surface coatings is a property of mirror-like pigment particles that
      consists of remarkable bright spots over a darker surround under unidirectional
      illumination. We developed a novel nondestructive method to characterize sparkles
      based on the multispectral imaging technique, and we focused on automotive
      metallic coatings containing aluminum flake pigments. Multispectral imaging was
      done in the visible spectrum at different illumination angles around the test
      sample. Reflectance spectra at different spatial positions were mapped to color
      coordinates and visualized in different color spaces. Spectral analysis shows
      that sparkles exhibit higher reflectance spectra and narrower bandwidths.
      Colorimetric analysis indicates that sparkles present higher lightness values and
      are far apart from the bulk of color coordinates spanned by the surround. A box
      counting procedure was applied to examine the fractal organization of color
      coordinates in the CIE 1976 L*a*b* color space. A characteristic noninteger
      exponent was found at each illumination position. The exponent was independent of
      the illuminant spectra. Together, these results demonstrate that sparkles are
      extreme deviations relative to the surround and that their spectral properties
      can be described as fractal patterns within the color space. Multispectral
      reflectance imaging provides a powerful, noninvasive method for spectral
      identification and classification of sparkles from metal flake pigments on the
      micron scale. 

PMID- 24945785
TI  - Some insights on the description of gradient elution in reversed-phase liquid
      chromatography.
AB  - The so-called "fundamental equation for gradient elution" has been used for
      modeling the retention in gradient elution. In this approach, the instantaneous
      retention factor (k) is expressed as a function of the change in the modifier
      content (phi(ts )), ts being the time the solute has spent in the stationary
      phase. This approach can only be applied at constant flow rate and with gradients
      where the elution strength depends on the column length following a f(t-l/u)
      function, u being the linear mobile phase flow rate, and l the distance from the
      column inlet to the location where the solute is at time t measured from the
      beginning of the gradient. These limitations can be solved by using the here
      called "general equation for gradient elution", where k is expressed as a
      function of phi(t,l). However, this approach is more complex. In this work, a
      method that facilitates the integration of the "general equation" is described,
      which allows an approximate analytical solution with the quadratic retention
      model, improving the predictions offered by the "linear solvent strength model."
      It also offers direct information about the changes in the instantaneous modifier
      content and retention factor, and gives a meaning to the gradient retention
      factor. 

PMID- 24945786
TI  - Supervised learning with complex spikes and spike-timing-dependent plasticity.
AB  - One distinctive feature of Purkinje cells is that they have two types of
      discharge: in addition to simple spikes they fire complex spikes in response to
      input from the climbing fibers. These complex spikes have an initial rapid burst
      of spikes and spikelets followed by a sustained depolarization; in some models of
      cerebellar function this climbing fiber input supervises learning in Purkinje
      cells. On the other hand, synaptic plasticity is often thought to rely on the
      timing of pre-synaptic and post-synaptic spikes. It is suggested here that the
      period of depolarization following a complex spike, combined with a simple spike
      timing-dependent plasticity rule, gives a mechanism for the climbing fiber to
      supervise learning in the Purkinje cell. This proposal is illustrated using a
      simple simulation in which it is seen that the climbing fiber succeeds in
      supervising the learning. 

PMID- 24945787
TI  - Preparation and in vitro evaluation of strontium-doped calcium silicate/gypsum
      bioactive bone cement.
AB  - The combination of two or more bioactive components with different
      biodegradability could cooperatively improve the physicochemical and biological
      performances of the biomaterials. Here we explore the use of alpha-calcium
      sulfate hemihydrate (alpha-CSH) and calcium silicate with and without strontium
      doping (Sr-CSi, CSi) to fabricate new bioactive cements with appropriate
      biodegradability as bone implants. The cements were fabricated by adding
      different amounts (0-35 wt%) of Sr-CSi (or CSi) into the alpha-CSH-based pastes
      at a liquid-to-solid ratio of 0.4. The addition of Sr-CSi into alpha-CSH cements
      not only led to a pH rise in the immersion medium, but also changed the surface
      reactivity of cements, making them more bioactive and therefore promoting apatite
      mineralization in simulated body fluid (SBF). The impact of additives on long
      term in vitro degradation was evaluated by soaking the cements in Tris buffer,
      SBF, and alpha-minimal essential medium (alpha-MEM) for a period of five weeks.
      An addition of 20% Sr-CSi to alpha-CSH cement retarded the weight loss of the
      samples to 36% (in Tris buffer), 43% (in SBF) and 54% (in alpha-MEM) as compared
      with the pure alpha-CSH cement. However, the addition of CSi resulted in a
      slightly faster degradation in comparison with Sr-CSi in these media. Finally,
      the in vitro cell-ion dissolution products interaction study using human fetal
      osteoblast cells demonstrated that the addition of Sr-CSi improved cell viability
      and proliferation. These results indicate that tailorable bioactivity and
      biodegradation behavior can be achieved in gypsum cement by adding Sr-CSi, and
      such biocements will be of benefit for enhancing bone defect repair.

PMID- 24945788
TI  - Arylpyrrole oligomers as tunable anion receptors.
AB  - A novel type of arylpyrrole oligomer possessing an appropriate electropositive
      cavity has been designed, prepared and analysed for use as readily accessible
      receptors for negatively charged guests. Affinities of the receptors for various
      anions were determined by UV/Vis titration experiments and in depth insights into
      the host-guest interactions were gained by performing (1)H NMR titration
      experiments and X-ray crystallographic structure analyses. Experimentally
      determined association constants were correlated with the calculated maximum
      electrostatic potentials of the electropositive cavities of the receptors,
      allowing estimation of the strengths of host-guest associations in similar
      compounds. The joint contribution of aryl C-H and pyrrole N-H hydrogens was shown
      to be key to a strong guest association, resulting in the arylpyrrole oligomers
      being efficient anion receptors. 

PMID- 24945790
TI  - Meniscal repair in vivo using human chondrocyte-seeded PLGA mesh scaffold
      pretreated with platelet-rich plasma.
AB  - The objective of this study was to test the hypothesis that platelet-rich plasma
      (PRP) pretreatment on a poly-lactic-co-glycolic acid (PLGA) mesh scaffold
      enhances the healing capacity of the meniscus with human chondrocyte-seeded
      scaffolds in vivo, even when the seeded number of cells was reduced from 10
      million to one million. A flexible PLGA mesh scaffold was pretreated with PRP
      using a centrifugal technique. One million human articular chondrocytes were
      seeded onto the scaffold by dynamic oscillation. After 7 days, scaffolds were
      placed between human meniscal discs and were implanted subcutaneously in nude
      mice for 6 weeks (n = 16/group). Fluorescence microscopy demonstrated uniform
      attachment of the chondrocytes throughout the scaffolds 24 h following seeding.
      Cell attachment analysis revealed a significantly increased number of
      chondrocytes on PRP-pretreated than non-treated scaffolds (p < 0.05). Field
      emission scanning electron microscopy revealed chondrocytes attached to the PRP
      pretreated scaffolds interconnecting their cellular processes with the fibrin
      network at 24 h and day 7 of culture. Of the 16 constructs containing PRP
      pretreated scaffolds implanted in mice, six menisci healed completely, nine
      healed incompletely and one did not heal. Histological results from the 16
      control constructs containing non-treated scaffolds revealed that none had healed
      completely, four healed incompletely and 12 did not heal. The histological
      outcome between the groups was significantly different (p < 0.05). These findings
      suggest that human articular chondrocytes on PRP-pretreated PLGA mesh scaffolds
      demonstrate increased cell attachment and enhance the healing capacity of
      meniscus with a reduced number of seeding cells in a meniscal repair mouse model.
      Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24945791
TI  - Clonorcis sinensis eggs are associated with calcium carbonate gallbladder stones.
AB  - Calcium carbonate gallbladder stones were easily neglected because they were
      previously reported as a rare stone type in adults. The aim of this study was to
      investigate the relationship between calcium carbonate stones and Clonorchis
      sinensis infection. A total of 598 gallbladder stones were studied. The stone
      types were identified by FTIR spectroscopy. The C. sinensis eggs and DNA were
      detected by microscopic examination and real-time fluorescent PCR respectively.
      And then, some egg-positive stones were randomly selected for further SEM
      examination. Corresponding clinical characteristics of patients with different
      types of stones were also statistically analyzed. The detection rate of C.
      sinensis eggs in calcium carbonate stone, pigment stone, mixed stone and
      cholesterol stone types, as well as other stone types was 60%, 44%, 36%, 6% and
      30%, respectively, which was highest in calcium carbonate stone yet lowest in
      cholesterol stone. A total of 182 stones were egg-positive, 67 (37%) of which
      were calcium carbonate stones. The C. sinensis eggs were found adherent to
      calcium carbonate crystals by both light microscopy and scanning electron
      microscopy. Patients with calcium carbonate stones were mainly male between the
      ages of 30 and 60, the CO2 combining power of patients with calcium carbonate
      stones were higher than those with cholesterol stones. Calcium carbonate
      gallbladder stones are not rare, the formation of which may be associated with C.
      sinensis infection. 

PMID- 24945792
TI  - The xenoestrogens ethinylestradiol and bisphenol A regulate BCRP at the blood
      brain barrier of rats.
AB  - 1. Breast cancer resistance protein (BCRP) is an ABC-transporter at the blood
      brain barrier (BBB) facilitating efflux of xenobiotics into blood. Expression and
      function are regulated via estrogen-receptors (ERs). 2. 17alpha-Ethinylestradiol
      (EE2) and bisphenol A (BPA) represent two prominent xenoestrogens. We studied
      whether EE2 and BPA regulate BCRP function and expression upon a 6 h treatment in
      an ER-dependent manner in a rat BBB-ex-vivo-model. 3. Isolated brain capillaries
      were incubated with EE2 or BPA. BCRP function and expression were analyzed by
      confocal microscopy and Western-Blot. ERalpha-antagonist MPP and ER-antagonist
      ICI182.780 were used to study involvement of ERs. 4. EE2 and BPA down-regulated
      BCRP transport function and expression. EE2 effects occurred at pharmacologically
      relevant doses, BPA exhibited only weak influences. Down-regulation by EE2 was
      reversed by ICI but not MPP. BPA effects were not reversed by either antagonist.
      5. EE2 is a potent regulator of BCRP expression and function acting by ERbeta
      stimulation. Oral contraception could alter uptake of pharmaceuticals to the
      brain and might thus be considered as an origin of central nervous system (CNS)
      side-effects. EE2 could also present a novel co-treatment to improve CNS
      pharmacotherapy. BPA is a weak modulator of BCRP expression. Its effects appear
      not to be caused by ERs.

PMID- 24945793
TI  - Study on simultaneous recycling of EAF dust and plastic waste containing TBBPA.
AB  - In the present work we investigated the fates of zinc, lead, and iron present in
      electric arc furnace dust during thermal treatment of the dust with
      tetrabromobisphenol A (TBBPA) and tetrabromobisphenol A diglycidyl ether
      (TBBPADGE). Mixtures of these materials were compressed into pellets and heated
      in a laboratory-scale furnace at 550  degrees C for 80 min, under oxidizing and
      inert conditions. The solid, condensed, and gaseous-phase products were
      characterized using an array of analytical methods: scanning electron microscopy,
      X-ray diffraction, electron probe microscopy, inductively coupled plasma, ion
      chromatography, and gas chromatography. The results indicated that heating the
      mixtures under specific conditions enabled high separation of zinc and lead from
      iron-rich residues, by a bromination-evaporation process. In the case of
      TBBPADGE, a maximum of 85% of zinc and 81% of lead were effectively separated
      under the above conditions. The process is based on the reaction between the
      highly reactive HBr gas evolved during thermal degradation of the flame-retarded
      materials with zinc (ZnO and ZnFe2O4) and lead in the dust, followed by complete
      evaporation of the formed metallic bromides from the solid residue.

PMID- 24945795
TI  - Formation of hexagonal fullerene layers from neutral and negatively charged
      fullerenes in {(Ph3P)3Au(+)}2(C60(*-))2(C60).C6H4Cl2 containing gold cations with
      the C3v symmetry.
AB  - Fullerene salt {(Ph3P)3Au(+)}2(C60(*-))2(C60).C6H4Cl2 (1) containing (Ph3P)3Au(+)
      cations with the C3v symmetry has been obtained as single crystals. Hexagonal
      corrugated fullerene layers formed in 1 alternate with the layers consisting of
      (Ph3P)3Au(+) and C6H4Cl2 along the c axis. According to IR spectra and
      peculiarities of the crystal structure, the charge on fullerenes in the layers is
      evaluated to be -1 for two and close to zero for one C60. These fullerenes have
      different cationic surroundings, and positively charged gold atoms approach
      closer to C60(*-). Charged and neutral fullerenes are closely packed within
      hexagonal layers with an interfullerene center-to-center distance of 10.02 A and
      multiple short van der Waals C...C contacts. The distances between C60(*-) are
      essentially longer with an interfullerene center-to-center distance of 10.37 A
      due to corrugation of the layers, and no van der Waals contacts are formed in
      this case. As a result, each C60(*-) has only three negatively charged fullerene
      neighbors with rather long interfullerene distances providing only weak
      antiferromagnetic interaction of spins in the fullerene layers with a Weiss
      temperature of -5 K. 

PMID- 24945796
TI  - Estimation of the intake of phenol compounds from virgin olive oil of a
      population from southern Spain.
AB  - The objective of the study was to determine the mean polyphenol composition of
      different varieties of virgin olive oil (VOO) habitually consumed in the region
      of southern Spain and to estimate the dietary exposure to olive oil polyphenols
      in that population. There were statistically significant differences in total
      polyphenols among varieties, with the Picual variety containing the largest
      amount with a mean value of 591.8 mg kg(-1). The main phenolic compounds found in
      the VOOs under study were tyrosol and hydroxytyrosol. The highest amounts of both
      substances were found in Picual olive oils with concentrations of 2.3-6.6 mg kg(
      1). The total intake of polyphenols from VOO ranged between 8.2 mg day(-1) (SD =
      4.14) for the under 19 year olds and 21.3 mg day(-1) (SD = 3) for the over 50
      year olds. Some polyphenols, including tyrosol and hydroxytyrosol, were consumed
      principally as olive oil. The intake of these compounds in the studied population
      was in the range of 88.5-237.4 MUg day(-1). This has particular importance as
      recent studies have demonstrated that hydroxytyrosol helps to improve plasma
      lipids levels and repair oxidative damage related to cardiovascular disease.
      There was a greater dietary consumption of polyphenols in olive oil among the
      participants who more closely followed the Mediterranean diet pattern. A higher
      consumption of olive oil and therefore a greater exposure to polyphenols was
      observed in females versus males and in participants of normal weight versus
      those who were overweight. The total intake of polyphenols from VOO significantly
      increased with higher age, reflecting the greater intake of this oil by older
      people, who also show a closer adherence to the Mediterranean diet. The over 50
      year-old age group showed the greatest consumption of this olive oil and
      therefore of phenolic compounds, which are healthy protectors in the human diet
      that contribute to the acknowledged benefits of the Mediterranean diet.

PMID- 24945794
TI  - An animated landscape representation of CD4+ T-cell differentiation, variability,
      and plasticity: insights into the behavior of populations versus cells.
AB  - Recent advances in understanding CD4(+) T-cell differentiation suggest that
      previous models of a few distinct, stable effector phenotypes were too
      simplistic. Although several well-characterized phenotypes are still recognized,
      some states display plasticity, and intermediate phenotypes exist. As a framework
      for reexamining these concepts, we use Waddington's landscape paradigm, augmented
      with explicit consideration of stochastic variations. Our animation program
      "LAVA" visualizes T-cell differentiation as cells moving across a landscape of
      hills and valleys, leading to attractor basins representing stable or semistable
      differentiation states. The model illustrates several principles, including: (i)
      cell populations may behave more predictably than individual cells; (ii)
      analogous to reticulate evolution, differentiation may proceed through a network
      of interconnected states, rather than a single well-defined pathway; (iii)
      relatively minor changes in the barriers between attractor basins can change the
      stability or plasticity of a population; (iv) intrapopulation variability of gene
      expression may be an important regulator of differentiation, rather than
      inconsequential noise; (v) the behavior of some populations may be defined mainly
      by the behavior of outlier cells. While not a quantitative representation of
      actual differentiation, our model is intended to provoke discussion of T-cell
      differentiation pathways, particularly highlighting a probabilistic view of
      transitions between states. 

PMID- 24945797
TI  - Notice of concern: Murdoch B.E, Kuruvilla M.S, Goozee J.V. "Effect of speech rate
      manipulations on articulatory dynamics in severe traumatic brain injury: an EMA
      and EPG study".

PMID- 24945798
TI  - Pierced Lasso Bundles are a new class of knot-like motifs.
AB  - A four-helix bundle is a well-characterized motif often used as a target for
      designed pharmaceutical therapeutics and nutritional supplements. Recently, we
      discovered a new structural complexity within this motif created by a disulphide
      bridge in the long-chain helical bundle cytokine leptin. When oxidized, leptin
      contains a disulphide bridge creating a covalent-loop through which part of the
      polypeptide chain is threaded (as seen in knotted proteins). We explored whether
      other proteins contain a similar intriguing knot-like structure as in leptin and
      discovered 11 structurally homologous proteins in the PDB. We call this new
      helical family class the Pierced Lasso Bundle (PLB) and the knot-like threaded
      structural motif a Pierced Lasso (PL). In the current study, we use structure
      based simulation to investigate the threading/folding mechanisms for all the PLBs
      along with three unthreaded homologs as the covalent loop (or lasso) in leptin is
      important in folding dynamics and activity. We find that the presence of a small
      covalent loop leads to a mechanism where structural elements slipknot to thread
      through the covalent loop. Larger loops use a piercing mechanism where the free
      terminal plugs through the covalent loop. Remarkably, the position of the loop as
      well as its size influences the native state dynamics, which can impact receptor
      binding and biological activity. This previously unrecognized complexity of knot
      like proteins within the helical bundle family comprises a completely new class
      within the knot family, and the hidden complexity we unraveled in the PLBs is
      expected to be found in other protein structures outside the four-helix bundles.
      The insights gained here provide critical new elements for future investigation
      of this emerging class of proteins, where function and the energetic landscape
      can be controlled by hidden topology, and should be take into account in ab
      initio predictions of newly identified protein targets. 

PMID- 24945800
TI  - Forward genetic screening identifies a small molecule that blocks Toxoplasma
      gondii growth by inhibiting both host- and parasite-encoded kinases.
AB  - The simultaneous targeting of host and pathogen processes represents an untapped
      approach for the treatment of intracellular infections. Hypoxia-inducible factor
      1 (HIF-1) is a host cell transcription factor that is activated by and required
      for the growth of the intracellular protozoan parasite Toxoplasma gondii at
      physiological oxygen levels. Parasite activation of HIF-1 is blocked by
      inhibiting the family of closely related Activin-Like Kinase (ALK) host cell
      receptors ALK4, ALK5, and ALK7, which was determined in part by use of an
      ALK4,5,7 inhibitor named SB505124. Besides inhibiting HIF-1 activation, SB505124
      also potently blocks parasite replication under normoxic conditions. To determine
      whether SB505124 inhibition of parasite growth was exclusively due to inhibition
      of ALK4,5,7 or because the drug inhibited a second kinase, SB505124-resistant
      parasites were isolated by chemical mutagenesis. Whole-genome sequencing of these
      mutants revealed mutations in the Toxoplasma MAP kinase, TgMAPK1. Allelic
      replacement of mutant TgMAPK1 alleles into wild-type parasites was sufficient to
      confer SB505124 resistance. SB505124 independently impacts TgMAPK1 and ALK4,5,7
      signaling since drug resistant parasites could not activate HIF-1 in the presence
      of SB505124 or grow in HIF-1 deficient cells. In addition, TgMAPK1 kinase
      activity is inhibited by SB505124. Finally, mice treated with SB505124 had
      significantly lower tissue burdens following Toxoplasma infection. These data
      therefore identify SB505124 as a novel small molecule inhibitor that acts by
      inhibiting two distinct targets, host HIF-1 and TgMAPK1. 

PMID- 24945799
TI  - Transcriptional control of steroid biosynthesis genes in the Drosophila
      prothoracic gland by ventral veins lacking and knirps.
AB  - Specialized endocrine cells produce and release steroid hormones that govern
      development, metabolism and reproduction. In order to synthesize steroids, all
      the genes in the biosynthetic pathway must be coordinately turned on in
      steroidogenic cells. In Drosophila, the steroid producing endocrine cells are
      located in the prothoracic gland (PG) that releases the steroid hormone ecdysone.
      The transcriptional regulatory network that specifies the unique PG specific
      expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we
      show that two transcription factors, the POU-domain Ventral veins lacking (Vvl)
      and the nuclear receptor Knirps (Kni), have essential roles in the PG during
      larval development. Vvl is highly expressed in the PG during embryogenesis and is
      enriched in the gland during larval development, suggesting that Vvl might
      function as a master transcriptional regulator in this tissue. Vvl and Kni bind
      to PG specific cis-regulatory elements that are required for expression of the
      ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in
      a larval developmental arrest due to failure in ecdysone production. Furthermore,
      Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic
      hormone (PTTH) signaling in the PG, two major pathways that control ecdysone
      biosynthesis and PG cell growth. We also show that the transcriptional regulator,
      Molting defective (Mld), controls early biosynthetic pathway steps. Our data show
      that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional
      control of biosynthetic gene expression and indirectly by affecting PTTH and
      TOR/S6K signaling. This provides new insight into the regulatory network of
      transcription factors involved in the coordinated regulation of steroidogenic
      cell specific transcription, and identifies a new function of Vvl and Knirps in
      endocrine cells during post-embryonic development. 

PMID- 24945802
TI  - Isolate-dependent growth, virulence, and cell wall composition in the human
      pathogen Aspergillus fumigatus.
AB  - The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic
      sensitization and invasive disease in susceptible individuals. The significant
      genetic and phenotypic variability between and among clinical and environmental
      isolates are important considerations in host-pathogen studies of A. fumigatus
      mediated disease. We observed decreased radial growth, rate of germination, and
      ability to establish colony growth in a single environmental isolate of A.
      fumigatus, Af5517, when compared to other clinical and environmental isolates.
      Af5517 also exhibited increased hyphal diameter and cell wall beta-glucan and
      chitin content, with chitin most significantly increased. Morbidity, mortality,
      lung fungal burden, and tissue pathology were decreased in neutropenic Af5517
      infected mice when compared to the clinical isolate Af293. Our results support
      previous findings that suggest a correlation between in vitro growth rates and in
      vivo virulence, and we propose that changes in cell wall composition may
      contribute to this phenotype. 

PMID- 24945801
TI  - Cystic echinococcoses in Mongolia: molecular identification, serology and risk
      factors.
AB  - BACKGROUND: Cystic echinococcosis (CE) is a globally distributed cestode zoonosis
      that causes hepatic cysts. Although Echinococcus granulosus sensu stricto (s.s.)
      is the major causative agent of CE worldwide, recent molecular epidemiological
      studies have revealed that E. canadensis is common in countries where camels are
      present. One such country is Mongolia. METHODOLOGY/PRINCIPAL FINDINGS: Forty
      three human hepatic CE cases that were confirmed histopathologically at the
      National Center of Pathology (NCP) in Ulaanbaatar (UB) were identified by
      analysis of mitochondrial cox 1 gene as being caused by either E. canadensis
      (n=31, 72.1%) or E. granulosus s.s. (n=12, 27.9%). The majority of the E.
      canadensis cases were strain G6/7 (29/31, 93.5%). Twenty three haplotypes were
      identified. Sixteen of 39 CE cases with data on age, sex and province of
      residence were citizens of UB (41.0%), with 13 of the 16 cases from UB caused by
      E. canadensis (G6/7) (81.3%). Among these 13 cases, nine were children (69.2%).
      All pediatric cases (n  =  18) were due to E. canadensis with 17 of the 18 cases
      (94.4%) due to strain G6/7. Serum samples were available for 31 of the 43 CE
      cases, with 22 (71.0%) samples positive by ELISA to recombinant Antigen B8/1
      (rAgB). Nine of 10 CE cases caused by E. granulosus s.s. (90.0%) and 13 of 20 CE
      cases by E. canadensis (G6/7) (65.0%) were seropositive. The one CE case caused
      by E. canadensis (G10) was seronegative. CE cases caused by E. granulosus s.s.
      showed higher absorbance values (median value 1.131) than those caused by E.
      canadensis (G6/7) (median value 0.106) (p  =  0.0137). CONCLUSION/SIGNIFICANCE:
      The main species/strains in the study population were E. canadenis and E.
      granulossus s.s. with E. canadensis the predominant species identified in
      children. The reason why E. canadensis appears to be so common in children is
      unknown.

PMID- 24945803
TI  - Promoter-bound p300 complexes facilitate post-mitotic transmission of
      transcriptional memory.
AB  - A central hallmark of epigenetic inheritance is the parental transmission of
      changes in patterns of gene expression to progeny without modification of DNA
      sequence. Although, the trans-generational conveyance of this molecular memory
      has been traditionally linked to covalent modification of histone and/or DNA,
      recent studies suggest a role for proteins that persist or remain bound within
      chromatin to "bookmark" specific loci for enhanced or potentiated responses in
      daughter cells immediately following cell division. In this report we describe a
      role for p300 in enabling gene bookmarking by pre-initiation complexes (PICs)
      containing RNA polymerase II (pol II), Mediator and TBP. Once formed these
      complexes require p300 to enable reacquisition of protein complex assemblies,
      chromatin modifications and long range chromatin interactions that facilitate
      post-mitotic transmission of transcriptional memory of prior environmental
      stimuli. 

PMID- 24945804
TI  - Biogenesis of influenza a virus hemagglutinin cross-protective stem epitopes.
AB  - Antigenic variation in the globular domain of influenza A virus (IAV)
      hemagglutinin (HA) precludes effective immunity to this major human pathogen.
      Although the HA stem is highly conserved between influenza virus strains, HA stem
      reactive antibodies (StRAbs) were long considered biologically inert. It is now
      clear, however, that StRAbs reduce viral replication in animal models and protect
      against pathogenicity and death, supporting the potential of HA stem-based
      immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing
      immunogens and understanding StRAb effector functions require thorough
      comprehension of HA stem structure and antigenicity. Here, we study the
      biogenesis of HA stem epitopes recognized in cells infected with various drifted
      IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence
      (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic
      reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high
      avidity, potentially good news for producing effective monomeric HA stem
      immunogens. Though HA stem epitopes are nestled among several N-linked
      oligosaccharides, glycosylation is not required for full antigenicity. Rather, as
      N-linked glycans increase in size during intracellular transport of HA through
      the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4
      degrees C and well at 37 degrees C. A de novo designed, 65-residue protein binds
      the mature HA stem independently of temperature, consistent with a lack of N
      linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs
      bind recombinant HA carrying simple N-linked glycans in a temperature-independent
      manner. Chemical cross-linking experiments show that N-linked oligosaccharides
      likely influence StRAb binding by direct local effects rather than by globally
      modifying the conformational flexibility of HA. Our findings indicate that StRAb
      binding to HA is precarious, raising the possibility that sufficient immune
      pressure on the HA stem region could select for viral escape mutants with
      increased steric hindrance from N-linked glycans. 

PMID- 24945806
TI  - Efficacy, safety and feasibility of ultrasound-guided percutaneous microwave
      ablation for large hepatic hemangioma.
AB  - OBJECTIVE: To evaluate the efficacy, safety and feasibility of microwave ablation
      (MWA) for large (5-10 cm in diameter) hepatic hemangioma. METHODS: In all, 46
      patients with 47 large hepatic hemangiomas were treated with ultrasound-guided
      percutaneous MWA. The effect of MWA for all patients was evaluated by enhanced
      magnetic resonance imaging or computed tomography within two months after
      ablation. RESULTS: A total of 27 male and 19 female patients were enrolled, with
      an average age of 46 +/- 11 years. The average size of hemangiomas was 6.3 +/-
      1.4 cm (range 5.0-9.6 cm). The initial complete ablation rate was 91.5% (43/47)
      and the volume of ablated lesions was significantly reduced. The rate of complete
      necrosis was not associated with the tumor size or location (P = 0.899 and 0.758,
      respectively). The total complete ablation rate was 95.7% (45/47). Major
      complications included acute renal dysfunction, hyperbilirubinemia and pleural
      effusion. No procedure-related death occurred. The average hospitalization stay
      was 5.7 +/- 2.5 days (range 3-17 days). During a follow-up period of 18.2 months
      (range 4-40 months), one patient developed local tumor progression at the
      radiofrequency ablation site. Three patients had new hemangiomas in other sites
      of the liver. At the end of the study all patients were alive and no severe
      complications occurred. CONCLUSION: Image-guided MWA is an effective and safe
      treatment for large hepatic hemangiomas, and can potentially be regarded as the
      first-line therapy.

PMID- 24945808
TI  - Enhancing proton conduction in 2D Co-La coordination frameworks by solid-state
      phase transition.
AB  - We report that a new 2D 3d-4f phosphonate [Co(III)La(III)(notpH)(H2O)6]ClO4.5H2O
      (CoLa-II) can undergo a phase transition above 45  degrees C and 93% relative
      humidity, resulting in [H3O][CoLa(notp)(H2O)4]ClO4.3H2O (CoLa-III). The
      transition is accompanied by the release of the proton from intralayer to
      interlayer, and thus the proton conductivity of the material is increased by 1
      order of magnitude. 

PMID- 24945805
TI  - Broad cross-reactive epitopes of the H5N1 influenza virus identified by murine
      antibodies against the A/Vietnam/1194/2004 hemagglutinin.
AB  - There is an urgent need for a rapid diagnostic system to detect the H5 subtype of
      the influenza A virus. We previously developed monoclonal antibodies (mAbs)
      against the H5 hemagglutinin (HA) for use in a rapid diagnostic kit. In this
      study, we determined the epitopes of the anti-H5 HA murine mAbs OM-b, AY-2C2, and
      YH-1A1. Binding assays of the mAbs to different strains of H5 HAs indicated that
      OM-b and AY-2C2 cross-reacted with HAs from clades 1, 2.1.3.2, 2.2, and 2.3.4,
      whereas YH-1A1 failed to bind to those of clades 2.1.3.2 and 2.3.4. HA chimeras
      revealed that the epitopes for each of the mAbs were in the HA1 region. Analysis
      of escape mutants revealed that OM-b and AY-2C2 mAbs interacted mainly with amino
      acid residues D43 and G46, and the YH-1A1 mAb interacted with G139 and K or R140
      of H5 HA. Multiple alignments of H5 HA protein sequences showed that D43 and G46
      were very conserved among H5N1 HAs, except those in clade 2.2.1 and clade 7
      (88.7%). The epitope for YH-1A1 mAb was highly variable in the HAs of H5N1,
      although it was well conserved in those of H5N2-N9. The OM-b and AY-2C2 mAbs
      could bind to the HAs of clades 1.1 and 2.3.2.1 that are currently epidemic in
      Asia, and we conclude that these would be effective for the detection of H5N1
      infections in this region. 

PMID- 24945807
TI  - Nfatc2 and Tob1 have non-overlapping function in T cell negative regulation and
      tumorigenesis.
AB  - Nfatc2 and Tob1 are intrinsic negative regulators of T cell activation. Nfatc2
      deficient and Tob1-deficient T cells show reduced thresholds of activation;
      however, whether these factors have independent or overlapping roles in negative
      regulation of T cell responses has not been previously examined. Here, we show
      that Nfatc2 knockout (KO) but not Tob1 KO mice have age-associated accumulation
      of persistently activated T cells in vivo and expansion of the CD44+ memory cell
      compartment and age-associated lymphocytic infiltrates in visceral organs,
      without significant changes in numbers of CD4+CD25+Foxp3+ regulatory T cells
      (Treg). In vitro, CD4+CD25- "conventional" T cells (Tconvs) from both KO strains
      showed greater proliferation than wild type (WT) Tconvs. However, while Tregs
      from Nfatc2 KO mice retained normal suppressive function, Tregs from Tob1 KOs had
      enhanced suppressive activity. Nfatc2 KO Tconvs expanded somewhat more rapidly
      than WT Tconvs under conditions of homeostatic proliferation, but their
      accelerated growth capacity was negated, at least acutely, in a lymphoreplete
      environment. Finally, Nfatc2 KO mice developed a previously uncharacterized
      increase in B-cell malignancies, which was not accelerated by the absence of
      Tob1. The data thus support the prevailing hypothesis that Nfatc2 and Tob1 are
      non-redundant regulators of lymphocyte homeostasis. 

PMID- 24945813
TI  - Rubella Virus-associated Anterior Uveitis in a Vaccinated Patient: A Case Report.
AB  - Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and
      almost all cases in Europe show an active antibody production in the aqueous
      humor against rubella virus. Herein we report a case of a fully vaccinated
      patient with common variable immunodeficiency who developed unilateral Fuchs
      heterochromic uveitis secondary to rubella virus which was proven by intraocular
      fluid examination. Awareness of rubella associated anterior uveitis should remain
      also in vaccinated patients, especially those without a fully competent immune
      system. 

PMID- 24945812
TI  - Acute hepatitis C in HIV-1 infected Japanese Cohort: single center retrospective
      cohort study.
AB  - OBJECTIVES: HCV co-infection is a poor prognostic factor in HIV-1-infected
      patients. Although the number of newly reported patients who show seroconversion
      is increasing, the clinical features are still unclear, especially in Asian
      countries. DESIGN: A single-center retrospective cohort study of patients
      diagnosed between 2001-2012. METHODS: Acute hepatitis C (AHC) was diagnosed upon
      detection of high serum ALT (>100 IU) followed by anti-HCV seroconversion.
      Clinical characteristics, HIV-1-related immunological status and IL-28B genotypes
      (rs12979860, rs8099917) were collected. We compared these variables between
      patients with and without spontaneous clearance of HCV and between responders and
      non-responders to treatment with pegylated interferon (PEG-IFN) plus ribavirin.
      RESULTS: Thirty-five patients were diagnosed with AHC during the study period.
      The majority (96.9%) were MSM. Three were lost to follow-up. Seventy-five percent
      of patients with AHC (24/32) were asymptomatic and found incidentally to have
      high serum ALT. Compared to those who did not show spontaneous clearance,
      patients with spontaneous HCV viral clearance showed more symptoms and more
      severe abnormalities related to acute hepatitis. Spontaneous clearance was seen
      in 4 out of 28 patients with CC+TT genotype, but not in 6 patients with IL-28B
      CT+TG genotype. PEG-IFN plus ribavirin treatment was initiated in 12 out of 28
      cases without spontaneous clearance. The sustained virological response rate was
      high (81.8%, 9/11), even in cases with CT+TG genotype infected with HCV genotype
      1b (SVR 2/2). CONCLUSIONS: Careful attention to AHC is needed in HIV-1-infected
      MSM. Early diagnosis and PEG-IFN plus ribavirin treatment should be considered
      for AHC cases.

PMID- 24945811
TI  - Rapid birth-and-death evolution of imprinted snoRNAs in the Prader-Willi syndrome
      locus: implications for neural development in Euarchontoglires.
AB  - Imprinted small nucleolar RNAs (snoRNAs) are only found in eutherian genomes and
      closely related to brain functions. A complex human neurological disease, Prader
      Willi syndrome (PWS), is primarily attributed to the deletion of imprinted
      snoRNAs in chromosome 15q11-q13. Here we investigated the snoRNA repertoires in
      the PWS locus of 12 mammalian genomes and their evolution processes. A total of
      613 imprinted snoRNAs were identified in the PWS homologous loci and the gene
      number was highly variable across lineages, with a peak in Euarchontoglires.
      Lineage-specific gene gain and loss events account for most extant genes of the
      HBII-52 (SNORD115) and the HBII-85 (SNORD116) gene family, and remarkable high
      gene-birth rates were observed in the primates and the rodents. Meanwhile, rapid
      sequence substitution occurred only in imprinted snoRNA genes, rather than their
      flanking sequences or the protein-coding genes located in the same imprinted
      locus. Strong selective constraints on the functional elements of these imprinted
      snoRNAs further suggest that they are subjected to birth-and-death evolution. Our
      data suggest that the regulatory role of HBII-52 on 5-HT2CR pre-mRNA might
      originate in the Euarchontoglires through adaptive process. We propose that the
      rapid evolution of PWS-related imprinted snoRNAs has contributed to the neural
      development of Euarchontoglires. 

PMID- 24945814
TI  - Introgression from domestic goat generated variation at the major
      histocompatibility complex of Alpine ibex.
AB  - The major histocompatibility complex (MHC) is a crucial component of the
      vertebrate immune system and shows extremely high levels of genetic polymorphism.
      The extraordinary genetic variation is thought to be ancient polymorphisms
      maintained by balancing selection. However, introgression from related species
      was recently proposed as an additional mechanism. Here we provide evidence for
      introgression at the MHC in Alpine ibex (Capra ibex ibex). At a usually very
      polymorphic MHC exon involved in pathogen recognition (DRB exon 2), Alpine ibex
      carried only two alleles. We found that one of these DRB alleles is identical to
      a DRB allele of domestic goats (Capra aegagrus hircus). We sequenced 2489 bp of
      the coding and non-coding regions of the DRB gene and found that Alpine ibex
      homozygous for the goat-type DRB exon 2 allele showed nearly identical sequences
      (99.8%) to a breed of domestic goats. Using Sanger and RAD sequencing,
      microsatellite and SNP chip data, we show that the chromosomal region containing
      the goat-type DRB allele has a signature of recent introgression in Alpine ibex.
      A region of approximately 750 kb including the DRB locus showed high rates of
      heterozygosity in individuals carrying one copy of the goat-type DRB allele.
      These individuals shared SNP alleles both with domestic goats and other Alpine
      ibex. In a survey of four Alpine ibex populations, we found that the region
      surrounding the DRB allele shows strong linkage disequilibria, strong sequence
      clustering and low diversity among haplotypes carrying the goat-type allele.
      Introgression at the MHC is likely adaptive and introgression critically
      increased MHC DRB diversity in the genetically impoverished Alpine ibex. Our
      finding contradicts the long-standing view that genetic variability at the MHC is
      solely a consequence of ancient trans-species polymorphism. Introgression is
      likely an underappreciated source of genetic diversity at the MHC and other loci
      under balancing selection. 

PMID- 24945816
TI  - Safety and efficacy of biodegradable drug-eluting vs. bare metal stents: a meta
      analysis from randomized trials.
AB  - BACKGROUND: Biodegradable polymeric coatings have been proposed as a promising
      strategy to enhance biocompatibility and improve the delayed healing in the
      vessel. However, the efficacy and safety of biodegradable polymer drug-eluting
      stents (BP-DES) vs. bare metal stents (BMS) are unknown. The aim of this study
      was to perform a meta-analysis of randomized controlled trials (RCTs) comparing
      the outcomes of BP-DES vs. BMS. METHODS AND RESULTS: PubMed, Embase, and Cochrane
      Central Register of Controlled Trials (CENTRAL) were searched for randomized
      clinical trials, until December 2013, that compared any of approved BP-DES and
      BMS. Efficacy endpoints were target-vessel revascularization (TVR), target-lesion
      revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were
      death, myocardial infarction (MI), definite stent thrombosis (DST). The meta
      analysis included 7 RCTs with 2,409 patients. As compared with BMS, there was a
      significantly reduced TVR (OR [95% CI] = 0.37 [0.28-0.50]), ISLL (OR [95% CI] = 
      0.41 [-0.48-0.34]) and TLR (OR [95% CI] = 0.38 [0.27-0.52]) in BP-DES patients.
      However, there were no difference for safety outcomes between BP-DES and BMS.
      CONCLUSIONS: BP-DES is more effective in reducing ISLL, TVR and TLR, as safe as
      standard BMS with regard to death, ST and MI. Further large RCTs with long-term
      follow-up are warranted to better define the relative merits of BP-DES.

PMID- 24945817
TI  - Clinical predictive models for chemotherapy-induced febrile neutropenia in breast
      cancer patients: a validation study.
AB  - BACKGROUND: Predictive models for febrile neutropenia (FN) would be informative
      for physicians in clinical decision making. This study aims to validate a
      predictive model (Jenkin's model) that comprises pretreatment hematological
      parameters in early-stage breast cancer patients. PATIENTS AND METHODS: A total
      of 428 breast cancer patients who received neoadjuvant/adjuvant chemotherapy
      without any prophylactic use of colony-stimulating factor were included.
      Pretreatment absolute neutrophil counts (ANC) and absolute lymphocyte counts
      (ALC) were used by the Jenkin's model to assess the risk of FN. In addition, we
      modified the threshold of Jenkin's model and generated Model-A and B. We also
      developed Model-C by incorporating the absolute monocyte count (AMC) as a
      predictor into Model-A. The rates of FN in the 1st chemotherapy cycle were
      calculated. A valid model should be able to significantly identify high-risk
      subgroup of patients with FN rate >20%. RESULTS: Jenkin's model (Predicted as
      high-risk when ANC?3.1*10^9/L;ALC?1.5*10^9/L) did not identify any subgroups with
      significantly high risk (>20%) of FN in our population, even if we used different
      thresholds in Model-A(ANC?4.4*10^9/L;ALC?2.1*10^9/L) or
      B(ANC?3.8*10^9/L;ALC?1.8*10^9/L). However, with AMC added as an additional
      predictor, Model-C(ANC?4.4*10^9/L;ALC?2.1*10^9/L; AMC?0.28*10^9/L) identified a
      subgroup of patients with a significantly high risk of FN (23.1%). CONCLUSIONS:
      In our population, Jenkin's model, cannot accurately identify patients with a
      significant risk of FN. The threshold should be changed and the AMC should be
      incorporated as a predictor, to have excellent predictive ability.

PMID- 24945820
TI  - The effect of regional trauma networks on paediatric trauma care in an integrated
      adult service.
AB  - OBJECTIVE: Our study analyzes the impact of becoming a major trauma centre (MTC)
      on paediatric trauma workload in a centre outside a major city without specialist
      paediatric surgical services. METHODS: Paediatric 'trauma calls' presenting
      between 1 April 2010 and 31 March 2013 were retrospectively reviewed. As our
      centre became an MTC on 1 April 2012, our study population was split into 'pre
      MTC' and 'post-MTC' groups. Patient demographics, mechanism of injury, patient
      outcome, Injury Severity Score and results of radiological investigations were
      recorded. RESULTS: There were 132 paediatric trauma calls, with a 72% annual
      increase post-MTC. More children with minor injuries, according to the Injury
      Severity Score, were seen post-MTC (47.5 vs. 29.6%). Although the proportion of
      patients undergoing a CT scanning remained static, the actual number increased
      and a higher proportion were normal in the post-MTC group (72.9 vs. 52.4%). This
      contributed to a higher proportion of patients being discharged home directly
      from the emergency department post-MTC (47.5 vs. 36.6%). Practice moved away from
      targeted CT scanning, in favour of trauma scanning post-MTC. CONCLUSION: The
      implementation of a regional trauma network has led to a rise in paediatric
      trauma cases. Paediatric trauma patients tend to be less severely injured, but
      the proportion undergoing CT scanning has remained the same, and these scans are
      more likely to be normal. A more rational approach for imaging of paediatric
      trauma patients is required to reduce the potentially harmful effects of exposure
      to ionizing radiation, and criteria for implementing trauma calls in children
      should be reconsidered.

PMID- 24945819
TI  - Obscure recurrent gastrointestinal bleeding: a revealed mystery?
AB  - OBJECTIVE: Nowadays, capsule endoscopy (CE) is the first-line procedure after
      negative upper and lower gastrointestinal (GI) endoscopy for obscure
      gastrointestinal bleeding (OGIB). Approximately, two-thirds of patients
      undergoing CE for OGIB will have a small-bowel abnormality. However, several
      patients who underwent CE for OGIB had the source of their blood loss in the
      stomach or in the colon. The aim of the present study is to determine the
      incidence of bleeding lesions missed by the previous gastroscopy/colonoscopy with
      CE and to evaluate the indication to repeat a new complete endoscopic workup in
      subjects related to a tertiary center for obscure bleeding before CE. METHODS AND
      METHODS: We prospectively reviewed data from 637/1008 patients underwent to CE
      for obscure bleeding in our tertiary center after performing negative gastroscopy
      and colonoscopy. RESULTS: CE revealed a definite or likely cause of bleeding in
      stomach in 138/637 patients (yield 21.7%) and in the colon in 41 patients (yield
      6.4%) with a previous negative gastroscopy and colonoscopy, respectively. The
      lesions found were outside the small bowel in only 54/637 (8.5%) patients. In
      111/138 patients, CE found lesions both in stomach and small bowel (small-bowel
      erosions in 54, AVMs in 45, active small-bowel bleeding in 4, neoplastic lesions
      in 3 and distal ileum AVMs in 5 patients). In 24/41 (58.5%) patients, CE found
      lesions both in small bowel and colon (multiple small-bowel erosions in 15; AVMs
      in 8 and neoplastic lesion in 1 patients. All patients underwent endoscopic
      therapy or surgery for their nonsmall-bowel lesions. CONCLUSIONS: Lesions in
      upper or lower GI tract have been missed in about 28% of patients submitted to CE
      for obscure bleeding. CE may play an important role in identifying lesions missed
      at conventional endoscopy.

PMID- 24945821
TI  - Differential expression of miR-125a-5p and let-7e predicts the progression and
      prognosis of non-small cell lung cancer.
AB  - Aberrant expression of various microRNAs (miRNA) has shown diagnostic and
      prognostic significance in non-small cell lung cancer (NSCLC). qRT-PCR analysis
      confirmed altered expression of miR-125a-5p, let-7e, miR-30a, miR-30e and miR-30e
      3p in 70 paired tissue and serum samples from NSCLC patients. The reduced
      expression of miR-125a-5p, let-7e and miR-30e was strongly associated with NSCLC
      dedifferentiation. The lost expression of miR-125a-5p and let-7e was associated
      with shorter overall survival and let-7e was an independent prognostic factor for
      NSCLC patients. These five miRNA expressions should be further evaluated as
      biomarkers for the early detection and prognosis of NSCLC patients. 

PMID- 24945818
TI  - Peroxisomes are required for lipid metabolism and muscle function in Drosophila
      melanogaster.
AB  - Peroxisomes are ubiquitous organelles that perform lipid and reactive oxygen
      species metabolism. Defects in peroxisome biogenesis cause peroxisome biogenesis
      disorders (PBDs). The most severe PBD, Zellweger syndrome, is characterized in
      part by neuronal dysfunction, craniofacial malformations, and low muscle tone
      (hypotonia). These devastating diseases lack effective therapies and the
      development of animal models may reveal new drug targets. We have generated
      Drosophila mutants with impaired peroxisome biogenesis by disrupting the early
      peroxin gene pex3, which participates in budding of pre-peroxisomes from the ER
      and peroxisomal membrane protein localization. pex3 deletion mutants lack
      detectible peroxisomes and die before or during pupariation. At earlier stages of
      development, larvae lacking Pex3 display reduced size and impaired lipid
      metabolism. Selective loss of peroxisomes in muscles impairs muscle function and
      results in flightless animals. Although, hypotonia in PBD patients is thought to
      be a secondary effect of neuronal dysfunction, our results suggest that
      peroxisome loss directly affects muscle physiology, possibly by disrupting energy
      metabolism. Understanding the role of peroxisomes in Drosophila physiology,
      specifically in muscle cells may reveal novel aspects of PBD etiology. 

PMID- 24945822
TI  - Experimental and computational investigation on the gas phase reaction of ethyl
      formate with Cl atoms.
AB  - The rate coefficient for the gas-phase reaction of Cl atoms with ethyl formate
      was measured over the temperature range of 268-343 K using relative rate methods,
      with ethyl chloride as a reference compound. The temperature dependent relative
      rate coefficients for the ethyl formate + Cl reaction were measured, and the
      modified Arrhenius expression kethyl formate(268-343) = (2.54 +/- 0.57) * 10(-23)
      T(4.1) exp {-(981 +/- 102)/T} cm(3) molecule(-1) s(-1) was obtained with 2sigma
      error limits. The room temperature rate coefficient for the title reaction is
      (9.84 +/- 0.79) * 10(-12) cm(3) molecule(-1) s(-1), which is in good agreement
      with reported values. To complement the experimental measurement, computational
      methods were used to calculate the rate coefficient for the ethyl formate + Cl
      reaction atoms using canonical variational transition state theory (CVT) with
      small curvature tunneling (SCT) and the CCSD (T)/cc-pVDZ//M062X/6-31+g(d,p) level
      of theory. The temperature dependent Arrhenius expression was obtained to be 2.97
      * 10(-18) T(2.4) exp[-(390/T)] cm(3) molecule(-1) s(-1) over the temperature
      range of 200-400 K. The thermodynamic parameters and branching ratio were
      calculated. Also, the atmospheric lifetime and global warming potentials (GWPs)
      were calculated for ethyl formate. 

PMID- 24945823
TI  - Enhanced gene expression promoted by hybrid magnetic/cationic block copolymer
      micelles.
AB  - We report on novel gene delivery vector systems based on hybrid polymer-magnetic
      micelles. The hybrid micelles were prepared by codissolution of hydrophobically
      surface modified iron oxide and amphiphilic polystyrene-b-poly(quaternized 2
      vinylpyridine) block copolymer (PS-b-P2QVP) in organic solvent. After extensive
      dialysis against water, micelles with positively charged hydrophilic corona of
      PQVP and hydrophobic PS core were prepared, in which magnetic nanoparticles were
      randomly distributed. The hybrid micelles were used to form complexes with linear
      (salmon sperm, 2000 bp, corresponding to M(w) of 1.32 * 10(6) Da) and plasmid
      (pEGFP-N1, 4730 bp, corresponding to M(w) of 3.12 * 10(6) Da) DNA. The resulting
      magnetopolyplexes of phosphate:amine (P/N) ratios in the 0.05-20 range were
      characterized by light scattering, zeta-potential measurements, and transmission
      electron microscopy as well as cytotoxicity and gel retardation assays. The
      investigated systems displayed a narrow size distribution, particle dimensions
      below 360 nm, whereas their zeta-potential values varied from positive to
      negative depending of the P/N ratio. The resulting vector nanosystems exhibited
      low toxicity. They were able to introduce pEGFP-N1 molecules into the cells. The
      application of a magnetic field markedly boosted the transgene expression
      efficiency of the magnetopolyplexes, which was even superior to those of
      commercial transfectants such as Lipofectamine and dendritic polyethylenimine.

PMID- 24945824
TI  - Editorial comment.

PMID- 24945825
TI  - Variola type IB DNA topoisomerase: DNA binding and supercoil unwinding using
      engineered DNA minicircles.
AB  - Type IB topoisomerases unwind positive and negative DNA supercoils and play a key
      role in removing supercoils that would otherwise accumulate at replication and
      transcription forks. An interesting question is whether topoisomerase activity is
      regulated by the topological state of the DNA, thereby providing a mechanism for
      targeting the enzyme to highly supercoiled DNA domains in genomes. The type IB
      enzyme from variola virus (vTopo) has proven to be useful in addressing
      mechanistic questions about topoisomerase function because it forms a reversible
      3'-phosphotyrosyl adduct with the DNA backbone at a specific target sequence (5'
      CCCTT-3') from which DNA unwinding can proceed. We have synthesized supercoiled
      DNA minicircles (MCs) containing a single vTopo target site that provides highly
      defined substrates for exploring the effects of supercoil density on DNA binding,
      strand cleavage and ligation, and unwinding. We observed no topological
      dependence for binding of vTopo to these supercoiled MC DNAs, indicating that
      affinity-based targeting to supercoiled DNA regions by vTopo is unlikely.
      Similarly, the cleavage and religation rates of the MCs were not topologically
      dependent, but topoisomers with low superhelical densities were found to unwind
      more slowly than highly supercoiled topoisomers, suggesting that reduced torque
      at low superhelical densities leads to an increased number of cycles of cleavage
      and ligation before a successful unwinding event. The K271E charge reversal
      mutant has an impaired interaction with the rotating DNA segment that leads to an
      increase in the number of supercoils that were unwound per cleavage event. This
      result provides evidence that interactions of the enzyme with the rotating DNA
      segment can restrict the number of supercoils that are unwound. We infer that
      both superhelical density and transient contacts between vTopo and the rotating
      DNA determine the efficiency of supercoil unwinding. Such determinants are likely
      to be important in regulating the steady-state superhelical density of DNA
      domains in the cell. 

PMID- 24945826
TI  - Structure of CbpA J-domain bound to the regulatory protein Cbpm explains its
      specificity and suggests evolutionary link between Cbpm and transcriptional
      regulators.
AB  - CbpA is one of the six E. coli DnaJ/Hsp40 homologues of DnaK co-chaperones and
      the only one that is additionally regulated by a small protein CbpM, conserved in
      gamma-proteobacteria. CbpM inhibits the co-chaperone and DNA binding activities
      of CbpA. This regulatory function of CbpM is accomplished through reversible
      interaction with the N-terminal J-domain of CbpA, which is essential for the
      interaction with DnaK. CbpM is highly specific for CbpA and does not bind DnaJ
      despite the high degree of structural and functional similarity between the J
      domains of CbpA and DnaJ. Here we report the crystal structure of the complex of
      CbpM with the J-domain of CbpA. CbpM forms dimers and the J-domain of CbpA
      interacts with both CbpM subunits. The CbpM-binding surface of CbpA is highly
      overlapping with the CbpA interface for DnaK, providing a competitive model for
      regulation through forming mutually exclusive complexes. The structure also
      provides the explanation for the strict specificity of CbpM for CbpA, which we
      confirmed by making mutants of DnaJ that became regulated by CbpM. Interestingly,
      the structure of CbpM reveals a striking similarity to members of the MerR family
      of transcriptional regulators, suggesting an evolutionary connection between the
      functionally distinct bacterial co-chaperone regulator CbpM and the transcription
      regulator HspR. 

PMID- 24945827
TI  - Functional characterization of a novel family of acetylcholine-gated chloride
      channels in Schistosoma mansoni.
AB  - Acetylcholine is the canonical excitatory neurotransmitter of the mammalian
      neuromuscular system. However, in the trematode parasite Schistosoma mansoni,
      cholinergic stimulation leads to muscle relaxation and a flaccid paralysis,
      suggesting an inhibitory mode of action. Information about the pharmacological
      mechanism of this inhibition is lacking. Here, we used a combination of
      techniques to assess the role of cholinergic receptors in schistosome motor
      function. The neuromuscular effects of acetylcholine are typically mediated by
      gated cation channels of the nicotinic receptor (nAChR) family. Bioinformatics
      analyses identified numerous nAChR subunits in the S. mansoni genome but,
      interestingly, nearly half of these subunits carried a motif normally associated
      with chloride-selectivity. These putative schistosome acetylcholine-gated
      chloride channels (SmACCs) are evolutionarily divergent from those of nematodes
      and form a unique clade within the larger family of nAChRs. Pharmacological and
      RNA interference (RNAi) behavioral screens were used to assess the role of the
      SmACCs in larval motor function. Treatment with antagonists produced the same
      effect as RNAi suppression of SmACCs; both led to a hypermotile phenotype
      consistent with abrogation of an inhibitory neuromuscular mediator. Antibodies
      were then generated against two of the SmACCs for use in immunolocalization
      studies. SmACC-1 and SmACC-2 localize to regions of the peripheral nervous system
      that innervate the body wall muscles, yet neither appears to be expressed
      directly on the musculature. One gene, SmACC-1, was expressed in HEK-293 cells
      and characterized using an iodide flux assay. The results indicate that SmACC-1
      formed a functional homomeric chloride channel and was activated selectively by a
      panel of cholinergic agonists. The results described in this study identify a
      novel clade of nicotinic chloride channels that act as inhibitory modulators of
      schistosome neuromuscular function. Additionally, the iodide flux assay used to
      characterize SmACC-1 represents a new high-throughput tool for drug screening
      against these unique parasite ion channels. 

PMID- 24945829
TI  - DNMT3A silencing RASSF1A promotes cardiac fibrosis through upregulation of
      ERK1/2.
AB  - Cardiac fibrosis contributes to the pathogenesis of atrial fibrillation (AF). The
      molecular mechanisms underlying the cardiac fibrosis remain unclear. However, Ras
      association domain family 1 isoform A (RASSF1A) is a regulatory tumor suppressor,
      which is important for pathogenesis of cardiac fibrosis and fibroblasts
      activation. Moreover, DNA methylation plays a central role in the maintenance of
      cardiac fibrosis. DNA methyltransferases 3A (DNMT3A) is a critical participant in
      the epigenetic silencing of regulatory genes. Here, we report that the
      downregulation of RASSF1A in cardiac fibrosis is associated with DNMT3A.
      Treatment of cardiac fibroblasts with DNMT3A inhibitor 5-AzadC blocked
      proliferation. 5-AzadC also prevented the loss of RASSF1A expression that occurs
      during activated cardiac fibroblasts. To determine the underlying molecular
      mechanisms, we hypothesized that cardiac fibrosis is controlled by DNMT3A. We
      demonstrated that downregulation of RASSF1A is associated with cardiac fibrosis
      and fibroblasts activation. Knockdown of DNMT3A elevated RASSF1A expression in
      activated cardiac fibroblasts. Moreover, we investigated the effect of RASSF1A on
      the Ras/ERK pathway. Upregulation of p-ERK1/2 was detected in activated cardiac
      fibroblasts with decreased RASSF1A expression. Our results have shown that DNMT3A
      likely plays an essential role in RASSF1A mediated upregulation of ERK1/2 in rat
      cardiac fibrosis. DNMT3A and RASSF1A may serve as a new mechanism for cardiac
      fibrosis. 

PMID- 24945830
TI  - Validation of the Explorer(r) 2.0 test coupled to e-Reader(r) for the screening
      of antimicrobials in muscle from different animal species.
AB  - The Explorer((r)) 2.0 tube test is a microbial inhibition test for the screening
      of antimicrobial residues in food samples. The new e-Reader((r)) device coupled
      to Explorer((r)) 2.0 operates by incubation at a selected temperature,
      determination of the endpoint of the assay and interpretation to generate
      results. This system was validated for muscle samples according to the European
      Commission Decision 2002/657/EC. Sensitivity towards 25 substances from several
      groups of antimicrobials was investigated in a first step. Detection capabilities
      for six substances representing the six major antimicrobial groups were also
      determined in bovine muscle. The detection capabilities for amoxicillin (10 ug l(
      1)), cefalexin (200 ug l(-1)), doxycyclin (100 ug l(-1)), sulfamethazine (100 ug
      l(-1)), tylosin (100 ug l(-1)) and neomycin (200 ug l(-1)) were in all cases at
      or below the maximum residue limit (MRL). Specificity and applicability of the
      test were demonstrated with muscle samples from four animal species (bovine,
      porcine, ovine and poultry) and results were found to be satisfactory. Ruggedness
      was evaluated on negative and spiked samples with sulfamethazine as a
      representative antimicrobial. Neither false-positives nor false-negatives were
      detected when varying the sample volume, the time of pre-incubation, the
      temperature of incubation and the batch of the test. These results prove that
      Explorer((r)) 2.0 coupled to e-Reader((r)) is a valuable tool for the screening
      of a broad range of antimicrobials in muscle. This new methodology simplifies the
      analysis and increases the accuracy of interpretation of the test results since
      the endpoint of the assay is automatically determined and results are interpreted
      objectively.

PMID- 24945832
TI  - Novel high-efficiency crystalline-silicon-based compound heterojunction solar
      cells: HCT (heterojunction with compound thin-layer).
AB  - With an amorphous silicon (a-Si:H)/crystalline silicon (c-Si) heterojunction
      structure, the heterojunction with intrinsic thin-layer (HIT) solar cell has
      become one of the most promising technologies for c-Si based solar cells. By
      replacing a-Si:H thin films with appropriate compound semiconductors, we propose
      novel heterojunction structures which allow c-Si heterojunction solar cells to
      possess higher power conversion efficiencies than HIT solar cells. Several
      promising heterojunction candidates and hetero-structures have been proposed in
      this work, and this kind of novel c-Si compound heterojunction solar cell is
      denominated HCT (heterojunction with a compound thin-layer). The feasibilities of
      these novel HCT structures are further investigated by theoretical approaches,
      and the modeling results demonstrate the device performance improvement. Finally,
      this paper proclaims the compound selection standards and essentials of achieving
      high-efficiency HCT solar cells, which are guidelines for the real device
      implementation. 

PMID- 24945833
TI  - Healing the healer: stress and coping strategies in the field of temporary
      medical work.
AB  - Temporary medical workers provide a vital role for the medical profession. These
      individuals, however, occupy a unique work arrangement as professional-specific
      temporary workers. Temporary medical workers often find themselves bearing the
      burdens of both medical workers and temporary workers. In partnership with the
      largest medical temporary agency in the United States, we content analyzed the
      responses of 86 medical temporary workers, geared at uncovering the primary
      stressors and coping strategies this sample enacted. Our findings concluded that
      temporary medical workers experienced stressors associated with both their
      medical and temporary roles, although more stressors were associated with
      temporary work than with medical care. Participants also relied heavily on coping
      strategies that allowed them to avoid these stressors. 

PMID- 24945831
TI  - A central role for carbon-overflow pathways in the modulation of bacterial cell
      death.
AB  - Similar to developmental programs in eukaryotes, the death of a subpopulation of
      cells is thought to benefit bacterial biofilm development. However mechanisms
      that mediate a tight control over cell death are not clearly understood at the
      population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and
      alpha-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways,
      which are active during staphylococcal biofilm development, modulate cell death
      to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity
      potentiates cell death in cells by a mechanism dependent on intracellular
      acidification and respiratory inhibition, AlsSD activity effectively counters
      CidC action by diverting carbon flux towards neutral rather than acidic
      byproducts and consuming intracellular protons in the process. Furthermore, the
      physiological features that accompany metabolic activation of cell death bears
      remarkable similarities to hallmarks of eukaryotic programmed cell death,
      including the generation of reactive oxygen species and DNA damage. Finally, we
      demonstrate that the metabolic modulation of cell death not only affects biofilm
      development but also biofilm-dependent disease outcomes. Given the ubiquity of
      such carbon overflow pathways in diverse bacterial species, we propose that the
      metabolic control of cell death may be a fundamental feature of prokaryotic
      development. 

PMID- 24945828
TI  - Catecholamine autotoxicity. Implications for pharmacology and therapeutics of
      Parkinson disease and related disorders.
AB  - Several neurodegenerative diseases involve loss of catecholamine neurons
      Parkinson disease is a prototypical example. Catecholamine neurons are rare in
      the nervous system, and why they are vulnerable in PD and related disorders has
      been mysterious. Accumulating evidence supports the concept of "autotoxicity"
      inherent cytotoxicity of catecholamines and their metabolites in the cells in
      which they are produced. According to the "catecholaldehyde hypothesis" for the
      pathogenesis of Parkinson disease, long-term increased build-up of 3,4
      dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine,
      causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies,
      a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for
      the tendency of alpha-synuclein to precipitate in the cytoplasm of
      catecholaminergic neurons have also been mysterious. Since DOPAL potently
      oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis
      provides a link between alpha-synucleinopathy and catecholamine neuron loss in
      Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein
      are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of
      several processes, including decreased vesicular sequestration of cytoplasmic
      catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of
      alpha-synuclein, lead to conversion from the stability afforded by negative
      feedback regulation to the instability, degeneration, and system failure caused
      by induction of positive feedback loops. These dysfunctions result from diverse
      combinations of genetic predispositions, environmental exposures, stress, and
      time. The notion of catecholamine autotoxicity has several implications for
      treatment, disease modification, and prevention. Conversely, disease modification
      clinical trials would provide key tests of the catecholaldehyde hypothesis. 

PMID- 24945834
TI  - Gender dimorphism of the cardiac dysfunction in murine sepsis: signalling
      mechanisms and age-dependency.
AB  - Development of cardiac dysfunction is associated with increased morbidity and
      mortality in patients with sepsis. Increasing evidence shows that gender
      determines the degree of inflammatory response of the host and that females
      tolerate sepsis better than males. It is unknown whether gender affects the
      cardiac dysfunction in animals or patients with sepsis. To investigate this, male
      or female C57BL/6 mice were subjected to either lipopolysaccharide
      (LPS)/peptidoglycan (PepG) co-administration or cecal ligation and puncture
      (CLP). At 18 hours after LPS/PepG injection or 24 hours after CLP, cardiac
      function was evaluated by echocardiography. The septic insult caused a
      significant cardiac dysfunction in both genders. However, the cardiac dysfunction
      was significantly less pronounced in females in comparison with males subjected
      to LPS (3 mg/kg)/PepG (0.1 mg/kg) or CLP. Compared with males injected with LPS
      (3 mg/kg)/PepG (0.1 mg/kg), western blotting analysis of the myocardium from
      females injected with LPS/PepG revealed i) profound increases in phosphorylation
      of Akt and eNOS; ii) significant decreases in phosphorylation of IkappaBalpha,
      nuclear translocation of the NF-kappaB subunit p65, decreased expression of iNOS
      and decreased synthesis of TNF-alpha and IL-6 in the heart. However, the gender
      dimorphism of the cardiac dysfunction secondary to LPS/PepG was not observed when
      higher doses of LPS (9 mg/kg)/PepG (1 mg/kg) were used. In conclusion, the
      cardiac dysfunction caused by sepsis was less pronounced in female than in male
      mice. The protection of female hearts against the dysfunction associated with
      sepsis is (at least in part) attributable to cardiac activation of the Akt/eNOS
      survival pathway, decreased activation of NF-kappaB, and decreased expression of
      iNOS, TNF-alpha and IL-6. It should be noted that the observed gender dimorphism
      of the cardiac dysfunction in sepsis was not seen when a very severe stimulus
      (high dose of LPS/PepG co-administration) was used to cause cardiac dysfunction. 

PMID- 24945835
TI  - Images in anesthesiology: pneumocephalus resulting from basilar skull fracture.

PMID- 24945838
TI  - A case report of chronic frontal bone osteitis presenting with recurrent
      unilateral lid swelling.
AB  - Despite the advances in modern antimicrobial treatment, paranasal sinus disease
      remains relatively common. A case of chronic inflammatory frontal sinus disease
      presented with unilateral recurrent eyelid swelling. Clinical features and
      management in conjunction with ENT are discussed. An extensive literature search
      has shown only one other similar case reported in Russian language whose
      management details however are not available. 

PMID- 24945839
TI  - Renal cell carcinoma in an ectopic pelvic kidney in a patient presenting with
      acute urinary retention.
AB  - The incidence of renal cell carcinoma in a pelvic kidney is rare, and has only
      been described in a very small number of cases. We describe a case where an
      incidental ectopic kidney with invasive renal cell carcinoma was diagnosed during
      a separate emergency admission for acute urinary retention. 

PMID- 24945840
TI  - Incarcerated appendix in a Spigelian hernia.
AB  - Spigelian hernias are rare, making up only 1-2% of all hernias. Like other
      hernias, they may contain abdominal contents but are more likely to be
      incarcerated due to the small size of the fascial defect.(1) We describe here the
      case of a 71-year-old female with a 10-year history of right lower quadrant pain
      that remained undiagnosed despite multiple imaging studies. Prior to presentation
      the patient developed a new bulge and increasing pain at this site; an ultrasound
      revealed the presence of a bowel-containing hernia. The patient was taken
      urgently to the operating room for a laparoscopic Spigelian hernia repair, and
      was found to have an incarcerated appendix in the hernia. After the hernia was
      reduced, an appendectomy was performed and the hernia was repaired with
      biological mesh. Postoperatively, the patient did well, and her pain resolved. 

PMID- 24945836
TI  - Quantification of HTLV-1 clonality and TCR diversity.
AB  - Estimation of immunological and microbiological diversity is vital to our
      understanding of infection and the immune response. For instance, what is the
      diversity of the T cell repertoire? These questions are partially addressed by
      high-throughput sequencing techniques that enable identification of immunological
      and microbiological "species" in a sample. Estimators of the number of unseen
      species are needed to estimate population diversity from sample diversity. Here
      we test five widely used non-parametric estimators, and develop and validate a
      novel method, DivE, to estimate species richness and distribution. We used three
      independent datasets: (i) viral populations from subjects infected with human T
      lymphotropic virus type 1; (ii) T cell antigen receptor clonotype repertoires;
      and (iii) microbial data from infant faecal samples. When applied to datasets
      with rarefaction curves that did not plateau, existing estimators systematically
      increased with sample size. In contrast, DivE consistently and accurately
      estimated diversity for all datasets. We identify conditions that limit the
      application of DivE. We also show that DivE can be used to accurately estimate
      the underlying population frequency distribution. We have developed a novel
      method that is significantly more accurate than commonly used biodiversity
      estimators in microbiological and immunological populations. 

PMID- 24945841
TI  - A case of splenic torsion and rupture presenting as ruptured ectopic pregnancy.
AB  - Splenic torsion with rupture of spleen is an extremely rare phenomenon. The
      clinical picture mimics several common conditions which are causes of acute
      abdomen and so it is seldom detected pre-operatively. An 18 year old female
      patient was admitted with an acute abdomen and shock. The provisional diagnosis
      was of a ruptured ectopic pregnancy. Peri-operatively we found a spontaneous
      rupture of the spleen following torsion along with early intrauterine pregnancy.
      Splenectomy was carried out and patient recovered well. Our report confirms that
      this rare entity can present as an acute abdomen which is very difficult to
      diagnose preoperatively and can masquerade as ruptured ectopic pregnancy in women
      of childbearing age group. 

PMID- 24945837
TI  - Regulatory mechanisms that prevent re-initiation of DNA replication can be
      locally modulated at origins by nearby sequence elements.
AB  - Eukaryotic cells must inhibit re-initiation of DNA replication at each of the
      thousands of origins in their genome because re-initiation can generate genomic
      alterations with extraordinary frequency. To minimize the probability of re
      initiation from so many origins, cells use a battery of regulatory mechanisms
      that reduce the activity of replication initiation proteins. Given the global
      nature of these mechanisms, it has been presumed that all origins are inhibited
      identically. However, origins re-initiate with diverse efficiencies when these
      mechanisms are disabled, and this diversity cannot be explained by differences in
      the efficiency or timing of origin initiation during normal S phase replication.
      This observation raises the possibility of an additional layer of replication
      control that can differentially regulate re-initiation at distinct origins. We
      have identified novel genetic elements that are necessary for preferential re
      initiation of two origins and sufficient to confer preferential re-initiation on
      heterologous origins when the control of re-initiation is partially deregulated.
      The elements do not enhance the S phase timing or efficiency of adjacent origins
      and thus are specifically acting as re-initiation promoters (RIPs). We have
      mapped the two RIPs to ~ 60 bp AT rich sequences that act in a distance- and
      sequence-dependent manner. During the induction of re-replication, Mcm2-7
      reassociates both with origins that preferentially re-initiate and origins that
      do not, suggesting that the RIP elements can overcome a block to re-initiation
      imposed after Mcm2-7 associates with origins. Our findings identify a local level
      of control in the block to re-initiation. This local control creates a complex
      genomic landscape of re-replication potential that is revealed when global
      mechanisms preventing re-replication are compromised. Hence, if re-replication
      does contribute to genomic alterations, as has been speculated for cancer cells,
      some regions of the genome may be more susceptible to these alterations than
      others.

PMID- 24945843
TI  - A rare case of breast carcinoma presenting with paraneoplastic cerebellar
      degeneration.
AB  - This case report highlights the importance of a high index of suspicion for
      breast cancer in a young patient with rapidly progressive neurological
      dysfunction, a family history of breast cancer and an asymptomatic breast lump. 

PMID- 24945842
TI  - Infected mesenteric ileocaecal dermoid cyst in a child.
AB  - Mesenteric dermoid cysts are a rare cause of abdominal pain. Although dermoid
      cysts occur in many parts of the body there have been only a few case reports
      involving the bowel mesentery. We present a case of a symptomatic mesenteric
      dermoid cyst involving the ileocaecal junction in a child. 

PMID- 24945844
TI  - Multiple intestinal perforations as a primary manifestation of abdominal
      tuberculosis in a HIV-infected patient.
AB  - Abdominal tuberculosis (TB) is the sixth commonest extra-pulmonary TB form after
      lymphatic, genitourinary, bone and joint, miliary and meningeal tuberculosis.
      Perforation is a serious and uncommon complication of abdominal tuberculosis
      which can occur even during the treatment. A 30-year-old man was admitted with a
      three-day history of abdominal pain who had emergency surgery for multiple
      perforations of the distal ileum. 

PMID- 24945845
TI  - Portal venous gas and pneumatosis intestinalis. Rare radiological signs in a rare
      complication of Meckel's diverticulum.
AB  - Portal vein gas is an uncommon ominous radiological sign usually harbouring an
      intra abdominal catastrophe. When accompanied by pneumatosis intestinalis, it is
      more predictive of bowel ischemia. We present a case presented with both signs,
      who suffered from a rare complication of Meckel's diverticulum. 

PMID- 24945846
TI  - Inflamed Meckel's diverticulum secondary to a giant faecalith: a rare
      presentation of acute abdominal pain in an adult.
AB  - Meckel's diverticulae can present with symptoms and signs mimicking acute
      appendicitis. We present the case of a healthy 35-year old male who was suspected
      of having acute appendicitis but at operation was found to have an inflamed
      Meckel's diverticulum containing a giant faecalith, which had caused ischaemic
      necrosis due to a pressure effect. Post-operatively the patient admitted to a
      year of recurrent bouts of severe colicky abdominal pain, when running. 

PMID- 24945847
TI  - The Red Rectum (Carpet villous adenoma of the rectum).
AB  - Carpeted villous adenomas of rectum may be extensive and not suitable for
      transanal excision or Endoscopic mucosal resection. We present a case of such
      lesion extending from anorectal junction to rectosigmoid region. After biopsy and
      staging, this was managed by a sphincter saving procedure, i.e. a combination of
      transabdominal total mesorectal excision and transanal intersphincteric
      dissection, with acceptable functional outcome with 8 years of follow up. 

PMID- 24945849
TI  - On the photostability of peptides after selective photoexcitation of the
      backbone: prompt versus slow dissociation.
AB  - Vulnerability of biomolecules to ultraviolet radiation is intimately linked to
      deexcitation pathways: photostability requires fast internal conversion to the
      electronic ground state, but also intramolecular vibrational redistribution and
      cooling on a time scale faster than dissociation. Here we present a protocol to
      disentangle slow and non-hazardous statistical dissociation from prompt cleavage
      of peptide bonds by 210 nm light based on experiments on protonated peptides
      isolated in vacuo and tagged by 18-crown-6 ether (CE). The weakest link in the
      system is between the charged site and CE, which is remote from the initial site
      of excitation. Hence loss of CE serves as direct proof that energy has reached
      the charge-site end, leaving the backbone intact. Our work demonstrates that
      excitation of tertiary amide moieties (proline linkages) results in both prompt
      dissociation and statistical dissociation after energy randomisation over all
      vibrational degrees of freedom. 

PMID- 24945848
TI  - Madurella mycetomatis is highly susceptible to ravuconazole.
AB  - The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory
      because of high recurrence rates, which often leads to complications and
      unnecessary amputations, and its comparatively high cost in endemic areas. Hence,
      an effective and affordable drug is required to improve therapeutic outcome.
      E1224 is a potent orally available, broad-spectrum triazole currently being
      developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly
      converted to ravuconazole. Plasma levels of E1224 are low and transient, and its
      therapeutically active moiety, ravuconazole is therapeutically active. In the
      present study, the in vitro activity of ravuconazole against Madurella
      mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and
      compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent
      activity with MICs ranging between <= 0.002 and 0.031 ug/ml, which were
      significantly lower than the MICs reported for ketoconazole and itraconazole. On
      the basis of our findings, E1224 with its resultant active moiety, ravuconazole,
      could be an effective and affordable therapeutic option for the treatment of
      eumycetoma.

PMID- 24945850
TI  - Simultaneous purification and fractionation of nucleic acids and proteins from
      complex samples using bidirectional isotachophoresis.
AB  - We report on our efforts to create an on-chip system to simultaneously purify and
      fractionate nucleic acids and proteins from complex samples using
      isotachophoresis (ITP). We have developed this technique to simultaneously
      extract extracellular DNA and proteins from human blood serum samples and deliver
      these to two separate output reservoirs on a chip. The purified DNA is compatible
      with quantitative polymerase chain reaction (qPCR), and proteins can be extracted
      so as to exclude albumin, the most abundant protein in serum. We describe
      significant remaining challenges in making this bidirectional method a robust and
      efficient technique. These challenges include managing channel surface adsorption
      of proteins, identifying the cause of observed reductions in low molecular weight
      proteins, and dealing with nonspecific binding of proteins and DNA. 

PMID- 24945851
TI  - Quantitative bond energetics in atomic-scale junctions.
AB  - A direct measurement of the potential energy surface that characterizes
      individual chemical bonds in complex materials has fundamental significance for
      many disciplines. Here, we demonstrate that the energy profile for metallic
      single-atom contacts and single-molecule junctions can be mapped by fitting
      ambient atomic force microscope measurements carried out in the near-equilibrium
      regime to a physical, but simple, functional form. We extract bond energies for
      junctions formed through metallic bonds as well as metal-molecule link bonds from
      atomic force microscope data and find that our results are in excellent
      quantitative agreement with density functional theory based calculations for
      exemplary junction structures. Furthermore, measurements from a large number of
      junctions can be collapsed to a single, universal force-extension curve, thus
      revealing a surprising degree of similarity in the overall shape of the potential
      surface that governs these chemical bonds. Compared to previous studies under
      ambient conditions where analysis was confined to trends in rupture force, our
      approach significantly expands the quantitative information extracted from these
      measurements, particularly allowing analysis of the trends in bond energy
      directly. 

PMID- 24945852
TI  - Identifying deficiencies in national and foreign medical team responses through
      expert opinion surveys: implications for education and training.
AB  - INTRODUCTION: Unacceptable practices in the delivery of international medical
      assistance are reported after every major international disaster; this raises
      concerns about the clinical competence and practice of some foreign medical teams
      (FMTs). The aim of this study is to explore and analyze the opinions of disaster
      management experts about potential deficiencies in the art and science of
      national and FMTs during disasters and the impact these opinions might have on
      competency-based education and training. METHOD: This qualitative study was
      performed in 2013. A questionnaire-based evaluation of experts' opinions and
      experiences in responding to disasters was conducted. The selection of the
      experts was done using the purposeful sampling method, and the sample size was
      considered by data saturation. Content analysis was used to explore the
      implications of the data. RESULTS: This study shows that there is a lack of
      competency-based training for disaster responders. Developing and performing
      standardized training courses is influenced by shortcomings in budget, expertise,
      and standards. There is a lack of both coordination and integration among teams
      and their activities during disasters. The participants of this study emphasized
      problems concerning access to relevant resources during disasters. CONCLUSION:
      The major findings of this study suggest that teams often are not competent
      during the response phase because of education and training deficiencies. Foreign
      medical teams and medically related nongovernmental organizations (NGOs) do not
      always provide expected capabilities and services. Failures in leadership and in
      coordination among teams are also a problem. All deficiencies need to be applied
      to competency-based curricula.

PMID- 24945854
TI  - Tribute to William C. Swope.

PMID- 24945855
TI  - Personal observations: William C. Swope.

PMID- 24945857
TI  - Publications of William C. Swope.

PMID- 24945858
TI  - Synthesis and spectral characterization of new homologous 1,3,5-triaryl-2
      pyrazolines: Influence of alkyloxy chain length on fluorescence.
AB  - Twelve new homologous 1,3,5-triaryl-2-pyrazolines (1c-12c) have been synthesized
      and characterized on the basis of their spectral (IR, (1)H and (13)C NMR and MS)
      data and microanalysis. The influence of alkyloxy chain length on absorption and
      fluorescence properties of 1c-12c was studied by UV-Vis and emission
      spectroscopy. For all the compounds, fluorescence was observed in the blue region
      of the visible spectrum. Furthermore, a strong influence of alkyloxy chain length
      was found on the emission intensity of 1,3,5-triaryl-2-pyrazolines, without
      causing any major blue- or red-shift in the emission wavelength (lambdamax(em)).
      The absorption and emission maxima (lambdamax(abs) and lambdamax(em)) for all the
      compounds were observed in the range of 408-416nm and 471-476nm, respectively.
      The effect of chloro-substituent present on the conjugated backbone of 1,3,5
      triaryl-2-pyrazoline moiety is also discussed. 

PMID- 24945859
TI  - Vibrational spectra (FT-IR and FT-Raman), molecular structure, natural bond
      orbital, and TD-DFT analysis of L-Asparagine Monohydrate by Density Functional
      Theory approach.
AB  - In this work we report the vibrational spectral analysis of l-Asparagine
      Monohydrate (LAM) molecule by using FT-IR and FT-Raman spectroscopic techniques.
      The equilibrium geometry, harmonic vibrational wavenumbers, various bonding
      features have been computed using density functional B3LYP method with 6
      311G(d,p) as basis set. Stability of the molecule arising from hyperconjugative
      interactions, charge delocalization have been analyzed using natural bond orbital
      (NBO) analysis. The results show that charge in electron density (ED) in sigma(*)
      and pi(*) antibonding orbitals and second order delocalization energies E((2))
      confirms the occurrence of Intramolecular Charge Transfer (ICT) within the
      molecule. The energy and oscillator strength calculated by Time-Dependent Density
      Functional Theory (TD-DFT) complements with the experimental findings. The
      simulated spectra satisfactorily coincide with the experimental spectra. 

PMID- 24945860
TI  - Kamlet-Taft and Catalan solvatochromism of some pi-expanded phenanthrimidazole
      derivatives - DFT analysis.
AB  - Some pi-expanded phenanthrimidazole derivatives have been synthesised and
      characterised by different spectral techniques. Kamlet-Taft and Catalan
      solvatochromism of synthesised phenanthrimidazole derivatives have been analysed.
      Non-linear optical (NLO) and natural bond orbital (NBO) analysis have been made
      by ab initio method to show intramolecular interactions. The energies of the HOMO
      and LUMO levels, the molecular electrostatic potential (MEP) energy surface, NBO
      studies have exploited the existence of intramolecular charge transfer (ICT)
      within the molecule. 

PMID- 24945853
TI  - Associations between single nucleotide polymorphisms in cellular viral receptors
      and attachment factor-related genes and humoral immunity to rubella vaccination.
AB  - BACKGROUND: Viral attachment and cell entry host factors are important for viral
      replication, pathogenesis, and the generation and sustenance of immune responses
      after infection and/or vaccination, and are plausible genetic regulators of
      vaccine-induced immunity. METHODS: Using a tag-SNP approach in candidate gene
      study, we assessed the role of selected cell surface receptor genes, attachment
      factor-related genes, along with other immune genes in the genetic control of
      immune response variations after live rubella vaccination in two independent
      study cohorts. RESULTS: Our analysis revealed evidence for multiple associations
      between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and
      other immune function-related genes and rubella-specific neutralizing antibodies
      after vaccination (meta p-value <0.05). CONCLUSION: Our results indicate that
      multiple SNPs from genes involved in cell adhesion, viral attachment, and viral
      entry, as well as others in genes involved in signaling and/or immune response
      regulation, play a role in modulating humoral immune responses following live
      rubella vaccination.

PMID- 24945861
TI  - ATR-FTIR spectroscopy and quantitative multivariate analysis of paints and
      coating materials.
AB  - The applicability of ATR-FTIR spectroscopy with partial least squares (PLS) data
      analysis was evaluated for quantifying the components of mixtures of paint
      binding media and pigments, and alkyd resins. PLS methods were created using a
      number of standard mixtures. Validation and measurement uncertainty estimation
      was carried out. Binary, ternary and quaternary mixtures of several common
      binding media and pigments were quantified, with standard measurement
      uncertainties in most cases below 3g/100g. Classes of components - aromatic
      anhydrides and alcohols - used in alkyd resin synthesis were also successfully
      quantified, with standard uncertainties in the range of 2-3g/100g. This is a more
      demanding application because in alkyd resins aromatic anhydrides and alcohols
      have reacted to form a polyester, and are not present in their original forms.
      Once a PLS method has been calibrated, analysis time and cost are significantly
      reduced from typical quantitative methods such as GC/MS. This is beneficial in
      the case of routine analysis where the components are known. 

PMID- 24945862
TI  - DFT simulations and vibrational spectra of 2-amino-2-methyl-1,3-propanediol.
AB  - The FTIR and FT-Raman spectra of 2-amino-2-methyl-1,3-propanediol were recorded
      in the regions 4000-400cm(-1) and 4000-50cm(-1) respectively. The structural and
      spectroscopic data of the molecule in the ground state were calculated using
      Hartee-Fock and density functional method (B3LYP) with the augmented-correlation
      consistent-polarized valence double zeta (aug-cc-pVDZ) basis set. The most stable
      conformer was optimized and the structural and vibrational parameters were
      determined based on this. The complete assignments were performed on the basis of
      the Potential Energy Distribution (PED) of the vibrational modes, calculated
      using Vibrational Energy Distribution Analysis (VEDA) 4 program. With the
      observed FTIR and FT-Raman data, a complete vibrational assignment and analysis
      of the fundamental modes of the compound were carried out. Thermodynamic
      properties and Mulliken charges were calculated using both Hartee-Fock and
      density functional method using the aug-cc-pVDZ basis set and compared. The
      calculated HOMO-LUMO energy gap revealed that charge transfer occurs within the
      molecule. (1)H and (13)C NMR chemical shifts of the molecule were calculated
      using Gauge-Independent Atomic Orbital (GIAO) method and were compared with
      experimental results. 

PMID- 24945863
TI  - A mechanosynthesized, sequential, cyclic fluorescent probe for mercury and iodide
      ions in aqueous solutions.
AB  - A fluorescent Hg(2+)-selective chemosensor, 2,5-dimethoxybenzaldehyde
      thiosemicarbazone (1), was quantitatively prepared by grinding 2,5
      dimethoxybenzaldehyde and thiosemicarbazide together in a ball mill for 15min.
      The excitation and emission maxima of compound 1 are 347 and 450nm, respectively.
      The reaction of this ligand with Hg(2+) was investigated by FT-IR, (1)H NMR, and
      fluorescence titration. Results show that the composition of the resulting Hg
      complex 1-Hg is 2:1 1:Hg, and that the S and imino N atoms serve as the binding
      sites of the ligand to the Hg(2+) ions. Coordination-assisted fluorescence
      quenching results show that compound 1 exhibits a highly selective fluorescence
      response to trace amounts of Hg(2+) in water. More importantly, the resulting
      complex 1-Hg can be used as a turn-on fluorescence probe for I(-) at a detection
      limit of 8.4*10(-8)M. Thus, compound 1 is a relatively stable, sequential, cyclic
      fluorescent probe for Hg(2+) and I(-). 

PMID- 24945865
TI  - Linear and nonlinear optical, mechanical, electrical and surface studies of a
      novel nonlinear optical crystal - manganese mercury thiocyanate (MMTC).
AB  - The highly efficient nonlinear optical single crystal of manganese mercury
      thiocyanate has been grown from slow evaporation solvent technique. The second
      harmonic generation and optical transmittance of the grown crystal are studied by
      Kurtz and Perry powder technique and spectroscopic absorbance spectrum.
      Mechanical behaviour is analyzed using Vickers microhardness test. The dielectric
      response of the grown crystal is studied as a function of the temperature and the
      results are discussed. Further, electronic properties such as plasma energy,
      Penngap, Fermi energy and electronic polarizability are evaluated. Third order
      nonlinear optical studies are performed using by single beam Z-scan technique
      using Nd:YAG laser and parameters such as nonlinear refractive index n2,
      absorption co-efficient beta and nonlinear optical susceptibility chi((3)) are
      evaluated for the grown crystal. The surface of the grown crystal is analyzed
      with field emission scanning electron microscope and atomic force microscope
      analyses. 

PMID- 24945864
TI  - Synthesis, photophysical and thin-film self-assembly properties of novel
      fluorescent molecules with carbon-carbon triple bonds.
AB  - Three novel fluorescent molecules with carbon-carbon triple bonds 2TBEA, 2TBDA
      and TEPEB are successfully designed and synthesized. Their thermal,
      photophysical, electrochemical, electronic and thin-film self-assembly properties
      were characterized. Three dyes showed typical photoluminescence (PL) emission
      behaviors, the PL intensities firstly increased and then decreased with gradually
      decreasing concentration. The appealing fluorescence properties indicated that
      three dyes could be used as good fluorescent materials. Additionally, the thin
      film self-assembly behaviors of three dyes were also investigated. The
      microstructures of their optical microscopy (OM) images exhibited high
      flexibility. Furthermore, SEM and AFM surface morphology of these self-assembly
      nanostructures revealed that three well-defined long-range order of rod-like and
      tube-like self-assembly systems exhibited interesting morphology properties.
      Therefore, three compounds may be of great interest for the development of
      organic thin-film materials. 

PMID- 24945866
TI  - Raman bandshape analysis on CH and CSC stretching modes of dimethyl sulfoxide in
      liquid binary mixture: comparative study with quantum-chemical calculations.
AB  - The interacting nature of dimethyl sulfoxide (DMSO) in binary mixtures has been
      carried out on CH and CSC stretching modes of vibration using chloroform (CLF),
      chloroform-d (CLFd), acetonitrile (ACN) and acetonitrile-d3 (ACNd) solvents. Peak
      frequencies of both the stretching modes show blue shift with the increase in
      solvent concentration. Variation of Raman bandwidth with the solvent
      concentration was discussed using different mechanisms. Ab initio calculation for
      geometry optimization and vibrational wavenumber calculation have been performed
      on monomer and dimer structures of DMSO to explain the experimentally observed
      Raman spectra. Theoretically calculated values are found in good agreement with
      the experimental results. Vibrational and reorientational relaxation times have
      been studied corresponding to solvent concentrations to elucidate the interacting
      mechanisms of binary mixtures. 

PMID- 24945868
TI  - Breeding programmes for smallholder sheep farming systems: II. Optimization of
      cooperative village breeding schemes.
AB  - A simulation study was conducted to optimize a cooperative village-based sheep
      breeding scheme for Menz sheep of Ethiopia. Genetic gains and profits were
      estimated under nine levels of farmers' participation and three scenarios of
      controlled breeding achieved in the breeding programme, as well as under three
      cooperative flock sizes, ewe to ram mating ratios and durations of ram use for
      breeding. Under fully controlled breeding, that is, when there is no gene flow
      between participating (P) and non-participating (NP) flocks, profits ranged from
      Birr 36.9 at 90% of participation to Birr 21.3 at 10% of participation. However,
      genetic progress was not affected adversely. When there was gene flow from the NP
      to P flocks, profits declined from Birr 28.6 to Birr -3.7 as participation
      declined from 90 to 10%. Under the two-way gene flow model (i.e. when P and NP
      flocks are herded mixed in communal grazing areas), NP flocks benefited from the
      genetic gain achieved in the P flocks, but the benefits declined sharply when
      participation declined beyond 60%. Our results indicate that a cooperative
      breeding group can be established with as low as 600 breeding ewes mated at a
      ratio of 45 ewes to one ram, and the rams being used for breeding for a period of
      two years. This study showed that farmer cooperation is crucial to effect genetic
      improvement under smallholder low-input sheep farming systems. 

PMID- 24945867
TI  - Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal
      failure.
AB  - Heart damage is widely present in patients with chronic kidney disease. Salt diet
      is the most important environmental factor affecting development of chronic renal
      failure and cardiovascular diseases. The proteins involved in chronic kidney
      disease -induced heart damage, especially their posttranslational modifications,
      remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy
      (chronic renal failure model) or sham operation were treated for 2 weeks with a
      normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment,
      iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for
      phosphoproteomic profiling of left ventricular free walls in these animals. A
      total of 1724 unique phosphopeptides representing 2551 non-redundant
      phosphorylation sites corresponding to 763 phosphoproteins were identified.
      During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%)
      phosphopeptides downregulated in chronic renal failure rats relative to sham
      rats. In chronic renal failure rats, high salt intake induced upregulation of 84
      (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database
      searches revealed that most of the identified phospholproteins were important
      signaling molecules such as protein kinases, receptors and phosphatases. These
      phospholproteins were involved in energy metabolism, cell communication, cell
      differentiation, cell death and other biological processes. The Search Tool for
      the Retrieval of Interacting Genes analysis revealed functional links among 15
      significantly regulated phosphoproteins in chronic renal failure rats compared to
      sham group, and 23 altered phosphoproteins induced by high salt intake. The
      altered phosphorylation levels of two proteins involved in heart damage, lamin A
      and phospholamban were validated. Expression of the downstream genes of these two
      proteins, desmin and SERCA2a, were also analyzed. 

PMID- 24945869
TI  - Still under the microscope: can a surgical aptitude test predict otolaryngology
      resident performance?
AB  - OBJECTIVES/HYPOTHESIS: Application to otolaryngology-head and neck surgery
      residency is highly competitive, and the interview process strives to select
      qualified applicants with a high aptitude for the specialty. Commonly employed
      criteria for applicant selection have failed to show correlation with proficiency
      during residency training. We evaluate the correlation between the results of a
      surgical aptitude test administered to otolaryngology resident applicants and
      their performance during residency. STUDY DESIGN: Retrospective study at an
      academic otolaryngology-head and neck surgery residency program. METHODS: Between
      2007 and 2013, 224 resident applicants participated in a previously described
      surgical aptitude test administered at a microvascular surgical station. The
      composite score and attitudinal scores for 24 consecutive residents who matched
      at our institution were recorded, and their residency performance was analyzed by
      faculty survey on a five-point scale. The composite and attitudinal scores were
      analyzed for correlation with residency performance score by regression analysis.
      RESULTS: Twenty-four residents were evaluated for overall quality as a clinician
      by eight faculty members who were blinded to the results of surgical aptitude
      testing. The results of these surveys showed good inter-rater reliability. Both
      the overall aptitude test scores and the subset attitudinal score showed
      reliability in predicting performance during residency training. CONCLUSIONS: The
      goal of the residency selection process is to evaluate the candidate's potential
      for success in residency and beyond. The results of this study suggest that a
      simple-to-administer clinical skills test may have predictive value for success
      in residency and clinician quality. LEVEL OF EVIDENCE: 4.

PMID- 24945871
TI  - Use of topical ice for local anesthesia for intravitreal injections.

PMID- 24945870
TI  - Analyzing receptor assemblies in the cell membrane using fluorescence anisotropy
      imaging with TIRF microscopy.
AB  - Signaling within and between animal cells is controlled by the many receptor
      proteins in their membrane. They variously operate as trans-membrane monomers and
      homo- or hetero-dimers, and may assemble with ion-channels: analyses thereof are
      needed in studies of receptor actions in tissue physiology and pathology.
      Interactions between membrane proteins are detectable when pre-labeled with
      fluorophores, but a much fuller analysis is achievable via advanced optical
      techniques on living cells. In this context, the measurement of polarization
      anisotropy in the emitted fluorescence has been the least exploited. Here we
      demonstrate its methodology and particular advantages in the study of receptor
      protein assembly. Through excitation in both TIRF and EPI fluorescence
      illumination modes we are able to quantify and suppress contributions to the
      signal from extraneous intra-cellular fluorescence, and we show that the loss of
      fluorescence-polarization measured in membrane proteins reports on receptor
      protein assembly in real time. Receptor monomers and homo-dimers in the cell
      membrane can be analyzed quantitatively and for homo-dimers only a single
      fluorescent marker is needed, thus suppressing ambiguities that arise in
      alternative assays, which require multiple label moieties and which are thus
      subject to stoichiometric uncertainty. 

PMID- 24945872
TI  - Patient-reported outcomes after acute nonvariceal upper gastrointestinal
      hemorrhage.
AB  - OBJECTIVE: Nonvariceal acute upper gastrointestinal bleeding (AUGIB) is often
      associated with significant blood loss and anemia. Both the bleeding episode
      itself and the subsequent anemia are likely to significantly impact a patient's
      health-related quality of life (HRQoL). Treating the anemia is essential to
      increase the hemoglobin levels. The HRQoL impact has not been investigated. This
      longitudinal study aimed to determine the relationship between anemia, HRQoL, and
      fatigue in patients after nonvariceal AUGIB. MATERIALS AND METHODS: A total of 97
      patients (51 males and 46 females; mean age 70 years) were followed in a
      longitudinal study with a 6-month follow-up. All patients had AUGIB and were
      anemic at inclusion. Anemia, HRQoL (EQ-5D-3L), and fatigue (using the
      Multidimensional Fatigue Inventory) were assessed at baseline, and at 1, 3, and 6
      months. The patients were initially included in an iron supplementation study.
      RESULTS: The patients' HRQoL increased and their fatigue levels decreased from
      baseline to month 3 and month 6. Approximately half of the patients had full
      health at month 3; similar results were observed in the general population. Three
      and six months after the bleeding episodes, neither the HRQoL nor fatigue was
      affected by the anemia. CONCLUSION: This study did not uncover relationships
      between anemia and HRQoL or anemia and fatigue after nonvariceal AUGIB.

PMID- 24945873
TI  - Scaffold pore size modulates in vitro osteogenesis of human adipose-derived
      stem/stromal cells.
AB  - Trabecular bone has an interconnected porous structure, which influences cellular
      responses, biochemical transport and mechanical strength. Appropriately mimicking
      this structural organization in biomaterial scaffolds can facilitate more robust
      bone tissue regeneration and integration by providing a native microenvironment
      to the cells. This study examined the effect of pore size on human adipose
      derived stem/stromal cell (ASC) osteogenesis within poly(epsilon-caprolactone)
      (PCL) scaffolds. Scaffold pore size was controlled by porogen leaching of custom
      made paraffin particles with three different size ranges: P200 (< 500 um), P500
      (500-1000 um), and P1000 (1000-1500 um). Scaffolds produced by leaching these
      particles exhibited highly interconnected pores and rough surface structures that
      were favorable for cell attachment and ingrowth. The osteogenic response of ASCs
      was evaluated following 3 weeks of in vitro culture using biochemical (ALP,
      Ca(2+)/DNA content), mechanical (compression test) and histological (H&E and von
      Kossa staining) analyses. It was observed that while the total number of cells
      was similar for all scaffolds, the cell distributions and osteogenic properties
      were affected by the scaffold pore size. ASCs were able to bridge smaller pores
      and grow uniformly within these scaffolds (P200) while they grew as a layer along
      the periphery of the largest pores (P1000). The cell-biomaterial interactions
      specific to the latter case led to enhanced osteogenic responses. The ALP
      activity and Ca(2+) deposition were doubled in P1000 scaffolds as compared to
      P200 scaffolds. A significant difference was observed between the compressive
      strength of unseeded and seeded P1000 scaffolds. Therefore, we demonstrated that
      the use of scaffolds with pores that are in the range of 1 mm enhances in vitro
      ASC osteogenesis, which may improve their performance in engineered bone
      substitutes.

PMID- 24945874
TI  - Entrustable professional activities and curricular milestones for fellowship
      training in pulmonary and critical care medicine: report of a multisociety
      working group.
AB  - This article describes the curricular milestones and entrustable professional
      activities for trainees in pulmonary, critical care, or combined fellowship
      programs. Under the Next Accreditation System of the Accreditation Council for
      Graduate Medical Education (ACGME), curricular milestones compose the curriculum
      or learning objectives for training in these fields. Entrustable professional
      activities represent the outcomes of training, the activities that society and
      professional peers can expect fellowship graduates to be able to perform
      unsupervised. These curricular milestones and entrustable professional activities
      are the products of a consensus process from a multidisciplinary committee of
      medical educators representing the American College of Chest Physicians (CHEST),
      the American Thoracic Society, the Society of Critical Care Medicine, and the
      Association of Pulmonary and Critical Care Medicine Program Directors. After
      consensus was achieved using the Delphi process, the document was revised with
      input from the sponsoring societies and program directors. The resulting lists
      can serve as a roadmap and destination for trainees, program directors, and
      educators. Together with the reporting milestones, they will help mark trainees'
      progress in the mastery of the six ACGME core competencies of graduate medical
      education. 

PMID- 24945875
TI  - Among-population variation in tolerance to larval herbivory by Anthocharis
      cardamines in the polyploid herb Cardamine pratensis.
AB  - Plants have two principal defense mechanisms to decrease fitness losses to
      herbivory: tolerance, the ability to compensate fitness after damage, and
      resistance, the ability to avoid damage. Variation in intensity of herbivory
      among populations should result in variation in plant defense levels if tolerance
      and resistance are associated with costs. Yet little is known about how levels of
      tolerance are related to resistance and attack intensity in the field, and about
      the costs of tolerance. In this study, we used information about tolerance and
      resistance against larval herbivory by the butterfly Anthocharis cardamines under
      controlled conditions together with information about damage in the field for a
      large set of populations of the perennial plant Cardamine pratensis. Plant
      tolerance was estimated in a common garden experiment where plants were subjected
      to a combination of larval herbivory and clipping. We found no evidence of that
      the proportion of damage that was caused by larval feeding vs. clipping
      influenced plant responses. Damage treatments had a negative effect on the three
      measured fitness components and also resulted in an earlier flowering in the year
      after the attack. Tolerance was related to attack intensity in the population of
      origin, i.e. plants from populations with higher attack intensity were more
      likely to flower in the year following damage. However, we found no evidence of a
      relationship between tolerance and resistance. These results indicate that
      herbivory drives the evolution for increased tolerance, and that changes in
      tolerance are not linked to changes in resistance. We suggest that the
      simultaneous study of tolerance, attack intensity in the field and resistance
      constitutes a powerful tool to understand how plant strategies to avoid negative
      effects of herbivore damage evolve. 

PMID- 24945877
TI  - Efficient C(sp3alkyl)-SCF3 bond formations via copper-mediated
      trifluoromethylthiolation of alkyl halides.
AB  - A general and convenient copper-mediated trifluoromethylthiolation of primary and
      secondary alkyl halides was described. Variation of the solvent, additives and
      time allowed optimization of the reaction. A wide range of alkyl halides were
      explored to give a set of alkyl trifluoromethyl thioethers in moderate to
      excellent yields. A variety of functional groups, including ethers, thioether,
      esters, nitriles, amides, and ketal groups, were well tolerated in the
      electrophilic partner. 

PMID- 24945876
TI  - Efficient pairwise composite likelihood estimation for spatial-clustered data.
AB  - Spatial-clustered data refer to high-dimensional correlated measurements
      collected from units or subjects that are spatially clustered. Such data arise
      frequently from studies in social and health sciences. We propose a unified
      modeling framework, termed as GeoCopula, to characterize both large-scale
      variation, and small-scale variation for various data types, including continuous
      data, binary data, and count data as special cases. To overcome challenges in the
      estimation and inference for the model parameters, we propose an efficient
      composite likelihood approach in that the estimation efficiency is resulted from
      a construction of over-identified joint composite estimating equations.
      Consequently, the statistical theory for the proposed estimation is developed by
      extending the classical theory of the generalized method of moments. A clear
      advantage of the proposed estimation method is the computation feasibility. We
      conduct several simulation studies to assess the performance of the proposed
      models and estimation methods for both Gaussian and binary spatial-clustered
      data. Results show a clear improvement on estimation efficiency over the
      conventional composite likelihood method. An illustrative data example is
      included to motivate and demonstrate the proposed method.

PMID- 24945878
TI  - Diagnosis and treatment of tuberculosis among children at an HIV care program in
      Dar es Salaam, Tanzania.
AB  - Diagnosis and treatment of tuberculosis is challenging in children with human
      immunodeficiency virus (HIV) infection. We describe the clinical features,
      diagnostic testing results, tuberculosis and HIV treatment and clinical outcomes
      of 57 HIV-infected children diagnosed with tuberculosis at the DarDar Pediatric
      Program in Dar es Salaam, Tanzania. In this cohort, tuberculosis was common,
      microbiologic studies were frequently negative and mortality was high. 

PMID- 24945879
TI  - Predicting mortality in HIV-infected children initiating highly active
      antiretroviral therapy in a resource-deprived setting.
AB  - BACKGROUND: While highly active antiretroviral therapy (HAART) programs have been
      scaled up across sub-Saharan Africa, no prognostic models for the prediction of
      mortality risk for children initiating HAART are widely available. Current
      clinical prediction tools for human immunodeficiency virus (HIV)-infected
      children are derived from pre-HAART data and therefore cannot predict mortality
      for children initiating HAART. The purpose of this study was to develop a
      mortality risk scoring system for HIV-infected children beginning HAART in a
      resource-deprived setting. METHODS: Observational data from HIV-infected children
      initiating HAART from December 2004 through March 2012 in Kinshasa, Democratic
      Republic of Congo, were analyzed. Cox proportional hazards models were
      constructed to assess associations between demographic and clinical
      characteristics at the time of HAART initiation and mortality. Each child
      received a model-based risk score predicting mortality after HAART initiation.
      RESULTS: By 31 March 2012, 1010 children had started HAART. One hundred three
      children (10.2%) died at a median of 5.3 months post-HAART initiation, yielding a
      mortality rate of 3.4 deaths per 100 child-years. The final mortality prediction
      model included undernutrition, low CD4 count, HIV symptoms, and low total
      lymphocyte count. These factors were highly predictive of mortality in the study
      population (C statistic = 0.79) and performed well when applied to the validation
      population (C statistic = 0.77). CONCLUSIONS: Mortality among children starting
      HAART in resource-deprived settings can be predicted using a simple scoring
      system incorporating several readily available factors. Identifying predictors of
      mortality will help clinicians target modifiable risk factors, such as
      undernutrition, which are not directly addressed by HAART.

PMID- 24945881
TI  - Nevirapine concentrations in preterm and low birth weight HIV-exposed infants:
      implications for dosing recommendations.
AB  - World Health Organisation guidelines recommend nevirapine 2 mg/kg/d for HIV
      exposed infants <2 kg, but 4-6 mg/kg/d for infants >2 kg. In 116 low birth weight
      infants, nevirapine 2 mg/kg/d until 14 days, and 4 mg/kg/d thereafter, was safe
      (1 mild possibly related rash) and achieved target plasma concentrations.
      Concentrations decreased with treatment duration. Routine dose increase at 14
      days should be considered. 

PMID- 24945882
TI  - Perceptions of electronic health record implementation: a statewide survey of
      physicians in Rhode Island.
AB  - OBJECTIVES: Although electronic health record use improves healthcare delivery,
      adoption into clinical practice is incomplete. We sought to identify the extent
      of adoption in Rhode Island and the characteristics of physicians and electronic
      health records associated with positive experience. METHODS: We performed a cross
      sectional study of data collected by the Rhode Island Department of Health for
      the Health Information Technology Survey 2009 to 2013. Survey questions included
      provider and practice demographics, health record information, and Likert-type
      scaled questions regarding how electronic health record use affected clinical
      practice. RESULTS: The survey response rate ranged from 50% to 65%, with 62% in
      2013. Increasing numbers of physicians in Rhode Island use an electronic health
      record. In 2013, 81% of physicians used one, and adoption varied by clinical
      subspecialty. Most providers think that electronic health record use improves
      billing and quality improvement but has not improved job satisfaction. Physicians
      with longer and more sophisticated electronic health record use report positive
      effects of introduction on all aspects of practice examined (P < .001). Older
      physician age is associated with worse opinion of electronic health record
      introduction (P < .001). Of the 18 electronic health record vendors most
      frequently used in Rhode Island, 5 were associated with improved job
      satisfaction. CONCLUSIONS: We report the largest statewide study of electronic
      health record adoption to date. We found increasing physician use in Rhode
      Island, and the extent of adoption varies by subspecialty. Although older
      physicians are less likely to be positive about electronic health record
      adoption, longer and more sophisticated use are associated with more positive
      opinions, suggesting acceptance will grow over time.

PMID- 24945883
TI  - Improved performances in polymer BHJ solar cells through frontier orbital tuning
      of small molecule additives in ternary blends.
AB  - Polymer solar cells fabricated in air under ambient conditions are of significant
      current interest, because of the implications in practicality of such devices.
      However, only moderate performance has been obtained for the air-processed
      devices. Here, we report that enhanced short circuit current density (JSC) and
      open circuit voltage (VOC) in air-processed poly(3-hexylthiophene) (P3HT)-based
      solar cells can be obtained by using a series of donor-acceptor dyes as the third
      component in the device. Power conversion efficiencies up to 4.6% were obtained
      upon addition of the dyes which are comparable to high-performance P3HT solar
      cells fabricated in controlled environments. Multilayer planar solar cells
      containing interlayers of the donor-acceptor dyes, revealed that along with
      infrared sensitization, an energy level cascade architecture and Forster
      resonance energy transfer could contribute to the enhanced performance. 

PMID- 24945880
TI  - Interruption of cART in clinical practice is associated with an increase in the
      long-term risk of subsequent immunosuppression in HIV-1-infected children.
AB  - BACKGROUND: Antiretroviral treatment interruption (TI) is not recommended in HIV
      infected children. We aimed to evaluate the context and consequences of TI in
      clinical practice. METHODS: We investigated the probability and risk factors of a
      first TI in the 483 children treated with combined ART (cART) in the ANRS French
      national pediatric cohort. Immunologic and virologic outcomes were compared
      between patients with TI (TI group) and those on continuous treatment (matched
      control group), from a baseline defined as the age at first interruption for the
      TI child and the corresponding age for the control child. RESULTS: At least one
      TI >= 3 months occurred in 42.4% of patients, at a median age of 8.0 years, for a
      median duration of 12.1 months. After cART initiation, the risk of TI was 7.0%
      (5.0-9.6) at 1 year and 30.3% (26.1-35.0) at 5 years and was higher for children
      starting treatment before 2000 and for children starting cART before 6 months of
      age. AIDS-free survival was similar, but severe immunosuppression occurred
      earlier in the TI group than in the control group (adjusted HR = 3.1; 1.0-9.1; P
      = 0.04). Four years after baseline, the proportion of patients with CD4% >= 25%
      was lower in the TI group than in the control group (52.0% vs. 72.0%; P < 0.01),
      even among children restarting cART at least 6 months earlier (aRR = 0.5; 0.3
      0.9; P = 0.03). CONCLUSIONS: The risk of TI in clinical practice has decreased
      but remains high. In intent-to-treat analysis, TI was associated with a greater
      risk of subsequent immunosuppression, even after cART resumption.

PMID- 24945885
TI  - Long-acting beta2-adrenergic agonist in pediatric and adolescent asthma patients,
      2003-2011.
AB  - OBJECTIVES: To evaluate changes in the dispensing patterns of long-acting beta2
      adrenergic agonist (LABA) in pediatric and adolescent asthma patients in relation
      to multiple Food and Drug Administration (FDA) regulatory activities from 2003 to
      2011. METHODS: We estimated LABA dispensing to pediatric asthma patients across
      three periods: 2003-2004 (after the first labeling change), 2005-2009 (after
      regulatory activities in 2005 and before 2010 LABA labeling change) and 2010-2011
      (after 2010 LABA labeling change), using the IMS Health Plan Claims database. We
      estimated dispensing patterns over time for single-ingredient (SI) LABA and fixed
      dose combination (FDC) of inhaled corticosteroid (ICS) and LABA (FDC-ICS/LABA).
      We also evaluated prior use of non-LABA asthma-control medication (ACM) before
      LABA initiation. RESULTS: Of the 147 862 pediatric and adolescent asthma patients
      who initiated a LABA during the entire study period, the majority (96%) were FDC
      ICS/LABA initiators. The proportion of SI-LABA among any LABA initiators was
      small and declined (9%, 4% and 2%, trend test p < 0.001) for the three periods.
      Among the patients who initiated, the proportions with prior use of an ACM (1-90
      days prior) were 35%, 36% and 39% for the three periods. CONCLUSIONS: The
      significant decline in the proportion of SI-LABA initiation over these years is
      consistent with FDA's recommendations. However, the favorable trend cannot be
      solely attributed to FDA activities as changes to clinical practice guidelines,
      and media publicity may have played a role. Investigating the reasons for the low
      ACM use before LABA initiation may inform approaches to further improve
      appropriate use of LABA in young asthma patients.

PMID- 24945884
TI  - Randomized trial of a health communication intervention for parents of children
      with asthma.
AB  - OBJECTIVE: To determine if a health communication intervention targeting parents
      of high-risk, urban, minority children with asthma could (i) improve parental
      perceptions of connectedness to and communication with their child's primary care
      providers (PCP) and (ii) decrease reliance on emergency departments (EDs) and
      other urgent care services for their child's asthma-related care. METHODS: The
      design was a single blind, parallel groups, randomized controlled trial. Parents
      were recruited from an ED-based asthma clinic serving primarily low-income,
      minority children in Washington, DC. The intervention involved face-to-face
      education on effective communication followed by a single booster call.
      Standardized instruments were administered to assess primary care connectedness
      and healthcare utilization at baseline and 2- and 6-months post-enrollment.
      RESULTS: A total of 150 parents of children 1-12 years old were randomized (77
      intervention and 73 usual care), and 137 (91%) were successfully followed for six
      months. Only at the two-month follow-up time-point, parents in the intervention
      group were significantly more likely to identify a PCP as the main source of
      their child's asthma care (adjusted odds ratio: 12.6, 95% confidence interval:
      1.1-142.1) and to report a significant reduction in ED visits for asthma care
      (adjusted incidence rate ratio: 0.3, 95% confidence interval: 0.1-0.8). There was
      no significant effect on parent communication self-efficacy or number of PCP
      visits. CONCLUSIONS: A brief, in-person health communication intervention for
      parents of high-risk children with asthma resulted in improved identification of
      PCPs as the usual source of asthma care and reduced reliance on EDs for asthma
      care, albeit only for two months post-intervention.

PMID- 24945886
TI  - Beyond co-pays and out-of-pocket costs: perceptions of health-related financial
      burden in managing asthma among African American women.
AB  - OBJECTIVE: The purpose of this study was to define perceptions of health-related
      financial burden based on the views of individuals who report these perceptions
      through qualitative approaches. METHODS: Four focus groups were conducted in
      Southeast Michigan with 26 African American women with asthma, recruited based on
      maximum variation sampling procedures. A semi-structured interview was employed
      by facilitators. Coded transcripts were analyzed for themes regarding dimensions
      of the meaning of financial burden. RESULTS: Major domains of financial burden
      identified included (1) high out-of-pocket expenses; (2) lost wages from
      exacerbations, inability to maintain a stable job and stress from making
      decisions about taking a sick day or coming to work; (3) transport costs; (4)
      both costs and stress of managing insurance eligibility and correcting erroneous
      bills. CONCLUSION: Greater awareness of factors that add to perceptions of
      financial burden might better equip researchers to develop interventions to help
      care teams manage such concerns with their patients.

PMID- 24945887
TI  - The use of a prospective audit proforma to improve door-to-mask times for acute
      exacerbations chronic obstructive pulmonary disease (COPD) requiring non-invasive
      ventilation (NIV).
AB  - Non-invasive ventilation (NIV) is an evidence based management of acidotic,
      hypercapnic exacerbations of COPD. Previous national and international audits of
      clinical practice have shown variation against guideline standards with
      significant delays in initiating NIV. We aimed to map the clinical pathway to
      better understand delays and reduce the door-to-NIV time to less than 3 hours for
      all patients with acidotic, hypercapnic exacerbations of COPD requiring this
      intervention, by mandating the use of a guideline based educational management
      proforma.The proforma was introduced at 7 acute hospitals in North London and
      Essex and initiated at admission of the patient. It was used to record the
      clinical pathway and patient outcomes until the point of discharge or death. Data
      for 138 patients were collected. 48% of patients commenced NIV within 3 hours
      with no reduction in door-to-mask time during the study period. Delays in
      starting NIV were due to: time taken for review by the medical team (101 minutes)
      and time taken for NIV to be started once a decision had been made (49 minutes).
      There were significant differences in door-to-NIV decision and mask times between
      differing respiratory on-call systems, p < 0.05). The introduction of the
      proforma had no effect on door-to-mask times over the study period. Main reasons
      for delay were related to timely access to medical staff and to NIV equipment;
      however, a marked variation in practice within these hospitals was been noted,
      with a 9-5 respiratory on-call system associated with shorter NIV initiation
      times.

PMID- 24945888
TI  - Viable and morphologically normal boar spermatozoa alter the expression of heat
      shock protein genes in oviductal epithelial cells during co-culture in vitro.
AB  - The principal aim of this study was to determine if boar spermatozoa influence
      the expression of four selected chaperone and heat-shock protein (HSP) genes
      namely clusterin (CLU), HSP90AA1, HSPA5, and HSPA8-in oviductal epithelial cells
      (OECs) during in vitro co-culture. All corresponding proteins of these genes were
      previously identified in a sperm-interacting, 70-kDa soluble fraction derived
      from apical plasma membranes of OECs. The present study also sought to determine
      whether or not: (i) spermatozoa must directly bind to OEC for an effect on gene
      expression to be elicited and (ii) reproductive and nonreproductive epithelial
      cell types (LLC-PK1, pig kidney) respond equivalently, in terms of alterations in
      chaperone and HSP gene expression, during co-culture with sperm. Spermatozoa
      induced a significant upregulation (P < 0.05) in HSP90AA1 and HSPA5 in OECs after
      3 hr, and in HSPA8 after 6 hr of co-culture when they were in direct contact with
      epithelial cells. Conversely, no upregulation of HSP transcription was observed
      when spermatozoa did not directly bind to OECs. Spermatozoa also induced a
      significant upregulation (P < 0.05) of the same three genes when in direct
      contact with LLC-PK1 cells, but the timing occurred later than with OECs.
      Interestingly, the extent of HSP gene upregulation induced by direct contact of
      spermatozoa with epithelial cells was dependent on sperm-binding index and on the
      viability and morphological quality of the bound sperm population. In conclusion,
      the upregulation of HSP genes caused by direct contact between spermatozoa and
      OECs, rather than nonreproductive epithelial cells, suggests HSPs could play an
      integral role in the modulation of sperm function in the oviductal reservoir.

PMID- 24945890
TI  - Multiple primary cancers as a guide to heritability.
AB  - There are approximately 100 genes which when mutated are known to predispose to
      one or more forms of cancer. Currently, genetic testing is offered for many of
      these, either as single genes or as multi-gene panels. Features of hereditary
      cancer include a positive family history of cancer, early age of onset and the
      appearance of multiple primary cancers in one individual. In some cases multiple
      cancers may be of the same site (e.g., bilateral breast cancer) and in other
      cases they may be at different sites. Various combinations of cancer sites may be
      indicative of specific cancer syndromes such as the breast ovarian cancer
      syndrome. Genetic testing should be offered to individuals who have experienced
      multiple primary cancers in some circumstances, the genetic counselor should
      review the ages of sites of cancer, their pathologic features and the family
      history of cancer as part of the pre-test evaluation. 

PMID- 24945891
TI  - Retinal vascular caliber and age-related macular degeneration in an Indian
      population from Singapore.
AB  - PURPOSE: To examine the association between retinal vascular caliber and early
      age-related macular degeneration (AMD) in an Indian population. METHODS: A total
      of 3112 Indian participants aged >=40 years from the population-based Singapore
      Indian Eye Study who had data available on retinal vascular caliber measurements
      and AMD status were included. Retinal arteriolar and venular calibers were
      measured from digital photographs using computer-assisted software according to a
      standardized protocol. Images of the macular region were graded according to the
      modified Wisconsin age-related maculopathy grading system. Right eyes were
      selected for analyses. Binary logistic regression models were used to assess the
      association, adjusting for age, sex, systolic blood pressure, total cholesterol,
      random blood glucose, body mass index, and the companion retinal vascular
      caliber. RESULTS: A total of 107 participants (3.4%) were diagnosed with early
      AMD. Neither arteriolar nor venular caliber was related to AMD. For early AMD,
      the age-, sex-, and companion retinal vascular caliber-adjusted odds ratio (OR)
      per standard deviation (SD) decrease in arteriolar caliber was 0.95 (95% CI 0.84
      1.31; p = 0.671), and per SD increase in venular caliber was OR: 0.96 (95% CI:
      0.77-1.20); p = 0.714. No trend was found after categorizing retinal vascular
      calibers into quartiles. Multivariate adjustment and stratified analyses did not
      alter these results. CONCLUSION: Retinal vascular calibers were not related to
      early AMD among Indian participants. These findings differ from those of several
      previous studies performed in Caucasian and Asian populations.

PMID- 24945889
TI  - Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones
      and puberty in boys.
AB  - Phthalates and BPA are known endocrine disruptors and exposure in pregnant
      mothers and children is ubiquitous. We explored the relationship of prenatal and
      childhood exposures with pubertal onset and sex hormones in boys (ages 8-14).
      Phthalate metabolites and BPA were measured in maternal 3rd trimester or
      childhood urine. Sex hormones DHEAS, estradiol, inhibin B, SHBG, and total
      testosterone were measured in serum. Adrenarche and puberty were assessed by
      pediatrician. Prenatal exposure to some phthalates was associated with decreased
      DHEAS and inhibin B levels, and with increased SHBG. Prenatal exposure to most
      phthalates and BPA was associated with greatly reduced odds of adrenarche (odds
      ratios [OR]=0.12-0.65) and slightly reduced odds of puberty (OR=0.50-0.98).
      Childhood exposure was not associated with adrenarche or puberty, but some
      phthalates and BPA were associated with increased SHBG levels and decreased total
      and free testosterone levels. 

PMID- 24945893
TI  - Academic medical product development: an emerging alliance of technology transfer
      organizations and the CTSA.
AB  - To bring the benefits of science more quickly to patient care, the NIH National
      Center Advancing Translational Sciences (NCATS) supports programs that enhance
      the development, testing, and implementation of new medical products and
      procedures. The NCATS clinical and translational science award (CTSA) program is
      central to that mission; creating an academic home for clinical and translational
      science and supporting those involved in the discovery and development of new
      health-related inventions. The technology transfer Offices (TTO) of CTSA-funded
      universities can be important partners in the development process; facilitating
      the transfer of medical research to the commercial sector for further development
      and ultimately, distribution to patients. The Aggregating Intellectual Property
      (IP) Working Group (AWG) of the CTSA public private partnerships key function
      committee (PPP-KFC) developed a survey to explore how CTSA-funded institutions
      currently interface with their respective TTOs to support medical product
      development. The results suggest a range of relationships across institutions;
      approximately half have formal collaborative programs, but only a few have well
      connected programs. Models of collaborations are described and provided as
      examples of successful CTSA/TTO partnerships that have increased the value of
      health-related inventions as measured by follow-on funding and industry
      involvement; either as a consulting partner or licensee. 

PMID- 24945892
TI  - Regulation of Hfq by the RNA CrcZ in Pseudomonas aeruginosa carbon catabolite
      repression.
AB  - Carbon Catabolite repression (CCR) allows a fast adaptation of Bacteria to
      changing nutrient supplies. The Pseudomonas aeruginosa (PAO1) catabolite
      repression control protein (Crc) was deemed to act as a translational regulator,
      repressing functions involved in uptake and utilization of carbon sources.
      However, Crc of PAO1 was recently shown to be devoid of RNA binding activity. In
      this study the RNA chaperone Hfq was identified as the principle post
      transcriptional regulator of CCR in PAO1. Hfq is shown to bind to A-rich
      sequences within the ribosome binding site of the model mRNA amiE, and to repress
      translation in vitro and in vivo. We further report that Crc plays an unknown
      ancillary role, as full-fledged repression of amiE and other CCR-regulated mRNAs
      in vivo required its presence. Moreover, we show that the regulatory RNA CrcZ,
      transcription of which is augmented when CCR is alleviated, binds to Hfq with
      high affinity. This study on CCR in PAO1 revealed a novel concept for Hfq
      function, wherein the regulatory RNA CrcZ acts as a decoy to abrogate Hfq
      mediated translational repression of catabolic genes and thus highlights the
      central role of RNA based regulation in CCR of PAO1. 

PMID- 24945895
TI  - Spinal cord stimulation for intractable pain evaluated by a collision study using
      somatosensory evoked potentials: a preliminary report.
AB  - OBJECTIVE: Appropriate stimulation of the dorsal column is required in order to
      achieve optimal control over pain by way of spinal cord stimulation (SCS). In
      this study, we objectively evaluated changes in somatosensory evoked potentials
      (SEPs) during a collision test in order to investigate whether paresthetic
      sensation or amount of pain reduction was correlated with the degree of dorsal
      column stimulation. MATERIALS AND METHODS: We studied 12 patients with
      intractable pain who underwent permanent SCS implantation. SEP collision was
      examined while recording the cortical SEP components elicited by posterior tibial
      nerve stimulation. A positive collision effect was observed when the SEP
      amplitude was clearly reduced by the SCS. RESULTS: Based on the SEP collision
      findings, the effects of SCS were classified into four patterns: positive
      collision with pain reduction (Type 1), positive collision without pain reduction
      (Type 2), negative collision with pain reduction (Type 3), and negative collision
      without pain reduction (Type 4). Type 1 was observed for well-known diseases in
      which SCS was very effective, whereas Type 2 was seen in poor candidates for
      dorsal column stimulation. Patients with poststroke pain exhibited various
      patterns including types 1, 2, and 3. One patient showed Type 4 patterning, and
      we recommended further SCS trials before the abandonment of SCS therapy for this
      patient. CONCLUSIONS: We show that SEP collision is useful for evaluating the
      degree of dorsal column stimulation needed as well as in considering factors
      related to differences between responders and nonresponders to SCS therapy.

PMID- 24945894
TI  - Novel synthetic (S,S) and (R,R)-secoisolariciresinol diglucosides (SDGs) protect
      naked plasmid and genomic DNA From gamma radiation damage.
AB  - Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain
      flaxseed. However, extraction methods are complex and are associated with low
      yield and high costs. Using a novel synthetic pathway, our group succeeded in
      chemically synthesizing SDG (S,S and R,R enantiomers), which faithfully
      recapitulates the properties of their natural counterparts, possessing strong
      antioxidant and free radical scavenging properties. This study further extends
      initial findings by now investigating the DNA-radioprotective properties of the
      synthetic SDG enantiomers compared to the commercial SDG. DNA radioprotection was
      assessed by cell-free systems such as: (a) plasmid relaxation assay to determine
      the extent of the supercoiled (SC) converted to open-circular (OC) plasmid DNA
      (pBR322) after exposure of the plasmid to gamma radiation; and (b) determining
      the extent of genomic DNA fragmentation. Exposure of plasmid DNA to 25 Gy of
      gamma radiation resulted in decreased supercoiled form and increased open
      circular form, indicating radiation-induced DNA damage. Synthetic SDG (S,S) and
      SDG (R,R), and commercial SDG at concentrations of 25-250 MUM significantly and
      equipotently reduced the radiation-induced supercoiled to open-circular plasmid
      DNA in a dose-dependent conversion. In addition, exposure of calf thymus DNA to
      50 Gy of gamma radiation resulted in DNA fragments of low-molecular weight
      (<6,000 bps), which was prevented in a dose-dependence manner by all synthetic
      and natural SDG enantomers, at concentrations as low as 0.5 MUM. These novel
      results demonstrated that synthetic SDG (S,S) and SDG (R,R) isomers and
      commercial SDG possess DNA-radioprotective properties. Such properties along with
      their antioxidant and free radical scavenging activity, reported earlier, suggest
      that SDGs are promising candidates for radioprotection for normal tissue damage
      as a result of accidental exposure during radiation therapy for cancer treatment.

PMID- 24945896
TI  - Reinterpretation of mouse thyroid changes under space conditions: the
      contribution of confinement to damage.
AB  - During space missions, astronauts work in a state of separation from their daily
      social environment and in physical confinement. It has been shown that
      confinement influences mood and brain cortical activity, but no data has been
      obtained with regard to its effect on the thyroid gland, the structure and
      function of which change during spaceflights. Here, we report the results of a
      study on the effects of confinement on mouse thyroid, which was implemented with
      the Mice Drawer System Facility maintained on the ground, a system used for
      spaceflight experiments. The results show that confinement changes the
      microscopic structure of the thyroid gland and that it exhibits symptoms similar
      to those that result from physiological and/or pathological hyperfunction. What
      is left unchanged, however, is the sphingomyelinase-thyrotropin receptor
      relationship, which is important for thyrotropin response with a consequential
      production of hormones that act on the metabolism of almost all tissues and
      reduces the production of calcitonin, a hormone involved in bone metabolism.
      During space missions, the overexpression of pleiotrophin, a widespread cytokine
      up-regulated after tissue injury that acts on bone remodeling, attenuates changes
      to the thyroid that are spaceflight-dependent; therefore we studied the thyroids
      of pleiotrophin-transgenic mice in the Mice Drawer System Facility. In
      confinement, pleiotrophin overexpression does not protect from the loss of
      calcitonin. The contribution of confinement to thyroid damage during spaceflights
      is discussed.

PMID- 24945897
TI  - Pathologic evaluation of normal and perfused term placental tissue.
AB  - This study reports for the 1st time the incidence and interobserver variation of
      morphologic findings in a series of 34 term placentas from pregnancies with
      normal outcome used for perfusion studies. Histologic evaluation of placental
      tissue is challenging, especially when it comes to defining "normal tissue"
      versus "pathologic lesions." A scoring system for registration of abnormal
      morphologic findings was developed. Light microscopic examination was performed
      independently by 2 pathologists, and interobserver variation was analyzed.
      Findings in normal and perfused tissue were compared and selected findings were
      tested against success parameters from the perfusions. Finally, the criteria for
      frequent lesions with fair to poor interobserver variation in the nonperfused
      tissue were revised and reanalyzed. In the perfused tissue, the perfusion
      artefact "trophoblastic vacuolization," which is believed to represent dilated
      transtrophoblastic channels, was reproducible and significantly correlated to the
      perfusion marker "fetal leakage." In longer perfusions, microscopy of the
      perfused cotyledon revealed bacteria in the fetal vessels. This finding led to an
      adjustment in the perfusion protocol with addition of antibiotics to the medium.
      In the "normal" tissue, certain lesions were very frequent and showed only fair
      or poor interobserver agreement. Revised minimum criteria for these lesions were
      defined and found reproducible. This study has emphasized the value of pathologic
      examination as a supplement in placental perfusion models. Examination of the
      perfused cotyledon for trophoblastic vacuolization is recommended as an
      additional quality marker in perfusion models. The study also underlines the need
      for exact definitions of abnormality in frequent placental lesions.

PMID- 24945898
TI  - Higher urinary heavy metal, arsenic, and phthalate concentrations in people with
      high blood pressure: US NHANES, 2009-2010.
AB  - BACKGROUND: A link between environmental chemicals and human health has emerged
      but not complete in risk factors. This work aimed to study the relationships of
      different sets of urinary environmental chemical concentrations and risk of high
      blood pressure (BP) in a national, population-based study. METHODS: Data was
      retrieved from United States National Health and Nutrition Examination Surveys,
      2009-2010, including demographics, BP readings and urinary environmental chemical
      concentrations. Analyses included t-test and survey-weighted logistic regression
      models. RESULTS: Urinary mercury concentrations were not associated with high BP
      (OR = 1.19, 95% CI 0.97-1.48, p = 0.095). Urinary cobalt (OR = 1.35, 95% CI 1.01
      1.81, p = 0.044), lead (OR = 1.77, 95% CI 1.31-2.38, p = 0.001), antimony (OR =
      1.37, 95% CI 1.09-1.72, p = 0.010) and tungsten (OR = 1.52, 95% CI 1.27-1.81, p <
      0.001) concentrations were observed to increase the risk of high BP. There are no
      clear associations between environmental parabens and high BP. The effect of
      environmental bisphenol A (OR = 1.14, 95% CI 1.00-1.30, p = 0.051) disappeared
      after additionally adjusting for subsample weighting (OR = 1.12, 95% CI 0.93
      1.35, p = 0.225). People with higher urinary mono-2-ethyl-5-carboxypentyl
      phthalate (OR = 1.26, 95% CI 1.00-1.58, p = 0.051), mono-n-butyl phthalate (OR =
      1.19, 95% CI 1.01-1.41, p = 0.042) and mono-n-methyl phthalate metabolites (OR =
      1.16, 95% CI 1.03-1.32, p = 0.021) tended to have high BP. Moreover, urinary o
      phenyl phenol concentrations (OR = 1.49, 95% CI 1.25-1.77, p < 0.001) and
      dimethylarsonic acid concentrations (OR = 1.35, 95% CI 1.06-1.73, p = 0.019) were
      also seen to be associated with high BP. CONCLUSIONS: Urinary environmental
      chemical concentrations were associated with risk of high BP, although the causal
      effect cannot be established. Elimination of environmental chemicals in humans
      would need to be continued.

PMID- 24945900
TI  - Direct synthesis of nitrogen-doped carbon nanosheets with high surface area and
      excellent oxygen reduction performance.
AB  - Graphene-like nitrogen-doped carbon nanosheets (NCN) have become a fascinating
      carbon-based material for advanced energy storage and conversion devices, but its
      easy, cheap, and environmentally friendly synthesis is still a grand challenge.
      Herein we directly synthesized porous NCN material via the facile pyrolysis of
      chitosan and urea without the requirement of any catalyst or post-treatment. As
      prepared material exhibits a very large BET surface area of ~1510 m(2) g(-1) and
      a high ratio of graphitic/pyridinic nitrogen structure (2.69 at. % graphitic N
      and 1.20 at. % pyridinic N). Moreover, compared to a commercial Pt/C catalyst,
      NCN displays excellent electrocatalytic activity, better long-term stability, and
      methanol tolerance ability toward the oxygen reduction reaction, indicating a
      promising metal-free alternative to Pt-based cathode catalysts in alkaline fuel
      cells. This scalable fabrication method supplies a low-cost, high-efficiency
      metal-free oxygen reduction electrocatalyst and also suggests an economic and
      sustainable route from biomass-based molecules to value-added nanocarbon
      materials.

PMID- 24945899
TI  - Optimization of the fractional precipitation of paclitaxel from a Taxus chinensis
      cell culture using response surface methodology and its isolation by consecutive
      high-speed countercurrent chromatography.
AB  - A consecutive preparation method for the isolation and purification of paclitaxel
      from the Taxus Chinensis cell culture was developed in this study. The process
      involved alkaline Al2O3 chromatography, fractional precipitation, and high-speed
      countercurrent chromatography. The original cell culture materials were first
      extracted with methanol using ultrasound-assisted extraction, and then the
      extract (the content of paclitaxel is 1.5%) was separated by alkaline Al2O3
      column chromatography. Subsequently, fractional precipitation was used to obtain
      paclitaxel. In particular, response surface methodology was used to optimize the
      factors of fractional precipitation (methanol concentration, material-to-solvent
      ratio, and precipitating time were optimized as 48.14%, 8.85 mg/mL, and 48.71 h,
      respectively) and the yield of fractional precipitation product was 30.64 +/-
      0.60 mg (the content of paclitaxel is 89.3%, 27.37 +/- 0.54 mg) from a 100 mg
      fraction by Al2O3 column separation (the content of paclitaxel is 32.4%). Then,
      the product was used for further isolation by high-speed countercurrent
      chromatography. About 1.00 g paclitaxel (200 +/- 2 mg in each loading) with a
      purity up to 99.61% was isolated from 1.25 g of fractional precipitation product
      with a solvent system of n-hexane/ethyl acetate/methanol/water (1.2:1.8:1.5:1.5,
      v/v/v/v) in one run of five consecutive sample loadings without exchanging a new
      solvent system.

PMID- 24945901
TI  - Unravelling the surface chemistry of metal oxide nanocrystals, the role of acids
      and bases.
AB  - We synthesized HfO2 nanocrystals from HfCl4 using a surfactant-free solvothermal
      process in benzyl alcohol and found that the resulting nanocrystals could be
      transferred to nonpolar media using a mixture of carboxylic acids and amines.
      Using solution (1)H NMR, FTIR, and elemental analysis, we studied the details of
      the transfer reaction and the surface chemistry of the resulting sterically
      stabilized nanocrystals. As-synthesized nanocrystals are charge-stabilized by
      protons, with chloride acting as the counterion. Treatment with only carboxylic
      acids does not lead to any binding of ligands to the HfO2 surface. On the other
      hand, we find that the addition of amines provides the basic environment in which
      carboxylic acids can dissociate and replace chloride. This results in stable,
      aggregate-free dispersions of HfO2 nanocrystals, sterically stabilized by
      carboxylate ligands. Moreover, titrations with deuterated carboxylic acid show
      that the charge on the carboxylate ligands is balanced by coadsorbed protons.
      Hence, opposite from the X-type/nonstoichiometric nanocrystals picture prevailing
      in literature, one should look at HfO2/carboxylate nanocrystals as systems where
      carboxylic acids are dissociatively adsorbed to bind to the nanocrystals. Similar
      results were obtained with ZrO2 NCs. Since proton accommodation on the surface is
      most likely due to the high Bronsted basicity of oxygen, our model could be a
      more general picture for the surface chemistry of metal oxide nanocrystals with
      important consequences on the chemistry of ligand exchange reactions. 

PMID- 24945903
TI  - Leukocyte profiles for western fence lizards, Sceloporus occidentalis, naturally
      infected by the malaria parasite Plasmodium mexicanum.
AB  - Plasmodium mexicanum is a malaria parasite that naturally infects the western
      fence lizard, Sceloporus occidentalis , in northern California. We set out to
      determine whether lizards naturally infected with this malaria parasite have
      different leukocyte profiles, indicating an immune response to infection. We used
      29 naturally infected western fence lizards paired with uninfected lizards based
      on sex, snout-to-vent length, tail status, and the presence-absence of
      ectoparasites such as ticks and mites, as well as the presence-absence of another
      hemoparasite, Schellackia occidentalis. Complete white blood cell (WBC) counts
      were conducted on blood smears stained with Giemsa, and the proportion of
      granulocytes per microliter of blood was estimated using the Avian Leukopet
      method. The abundance of each WBC class (lymphocytes, monocytes, heterophils,
      eosinophils, and basophils) in infected and uninfected lizards was compared to
      determine whether leukocyte densities varied with infection status. We found that
      the numbers of WBCs and lymphocytes per microliter of blood significantly
      differed (P < 0.05) between the 2 groups for females but not for males, whereas
      parasitemia was significantly correlated with lymphocyte counts for males, but
      not for females. This study supports the theory that infection with P. mexicanum
      stimulates the lizard's immune response to increase the levels of circulating
      WBCs, but what effect this has on the biology of the parasite remains unclear. 

PMID- 24945902
TI  - Hemodynamic directed CPR improves cerebral perfusion pressure and brain tissue
      oxygenation.
AB  - AIM: Advances in cardiopulmonary resuscitation (CPR) have focused on the
      generation and maintenance of adequate myocardial blood flow to optimize the
      return of spontaneous circulation and survival. Much of the morbidity associated
      with cardiac arrest survivors can be attributed to global brain hypoxic ischemic
      injury. The objective of this study was to compare cerebral physiological
      variables using a hemodynamic directed resuscitation strategy versus an absolute
      depth-guided approach in a porcine model of ventricular fibrillation (VF) cardiac
      arrest. METHODS: Intracranial pressure and brain tissue oxygen tension probes
      were placed in the frontal cortex prior to induction of VF in 21 female 3-month
      old swine. After 7 min of VF, animals were randomized to receive one of three
      resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest
      compressions (CCs) with depth titrated to a target systolic blood pressure of 100
      mmHg and titration of vasopressors to maintain coronary perfusion pressure
      (CPP)>20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard
      American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51):
      target CC depth of 51 mm with standard AHA epinephrine dosing. RESULTS: Cerebral
      perfusion pressures (CerePP) were significantly higher in the CPP-20 group
      compared to both D33 (p<0.01) and D51 (p=0.046), and higher in survivors compared
      to non-survivors irrespective of treatment group (p<0.01). Brain tissue oxygen
      tension was also higher in the CPP-20 group compared to both D33 (p<0.01) and D51
      (p=0.013), and higher in survivors compared to non-survivors irrespective of
      treatment group (p<0.01). Subjects with a CPP>20 mmHg were 2.7 times more likely
      to have a CerePP>30 mmHg (p<0.001). CONCLUSIONS: Hemodynamic directed
      resuscitation strategy targeting coronary perfusion pressure>20 mmHg following VF
      arrest was associated with higher cerebral perfusion pressures and brain tissue
      oxygen tensions during CPR.

PMID- 24945904
TI  - Development and evaluation of the rVP-ELISA for detection of antibodies against
      porcine parvovirus.
AB  - The gene encoding the VP2 protein of porcine parvovirus (PPV) was expressed in an
      insect-baculovirus system. The recombinant (r) VP2 was similar
      antigenically/functionally to the native capsid protein as demonstrated by
      hemagglutination (HA), Western blotting using PPV positive sera. The purified
      rVP2 proteins were used as coating antigen to establish a rVP-ELISA method for
      detection of PPV positive and negative sera from pigs. The optimal operating
      conditions of the rVP-ELISA were: the concentration of rVP2 proteins coated on
      the wells was 2 MUg/mL; the diluted concentration of serum was 1: 150 and that of
      the enzyme-labeled antibody was 1: 6000. A total of 596 sera were detected by
      this assay, and the average positive rate was 87%. Compared with France LSI kit,
      the result showed that the coincidence rate was 96.7%. In conclusion, the rVP2
      ELISA is a sensitive and specific method for detecting antibodies against PPV.

PMID- 24945905
TI  - Severe low back pain in patients with rheumatoid arthritis is associated with
      Disease Activity Score but not with radiological findings on plain X-rays.
AB  - OBJECTIVE: To investigate the prevalence and associated factors of severe low
      back pain (LBP) among patients with rheumatoid arthritis (RA). METHODS: This
      cross-sectional study included 201 patients with RA without prior spinal surgery.
      Severe LBP was defined as that with a visual analog scale (VAS) score of >= 50 mm
      within the previous 4 weeks. Lumbar lesions, sagittal alignment, and disc
      degeneration were evaluated by plain standing X-rays and magnetic resonance
      imaging. Associated factors of severe LBP were evaluated using multiple logistic
      regression analysis. RESULTS: Forty-eight patients (23.8%) had LBP with a VAS
      score of >= 50 mm. Multivariate analysis indicated that the associated factors
      for severe LBP were female, smoking, and moderate and high disease activity on
      the Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28
      ESR). There was no relationship between severe LBP and any radiological findings.
      Among DAS28-ESR subscores, patients with severe LBP had significantly higher
      tender joint counts and VAS scores for general health. CONCLUSIONS: The
      prevalence of severe LBP was relatively high in patients with RA. The factor most
      closely associated with severe LBP was Disease Activity Score, but not
      radiological findings. Severe LBP was related to the tender joint count or
      subjective complaints of RA.

PMID- 24945906
TI  - Solvation and protonation of coumarin 102 in aqueous media: a fluorescence
      spectroscopic and theoretical study.
AB  - The ground- and excited-state protonation of Coumarin 102 (C102), a fluorescent
      probe applied frequently in heterogeneous systems with an aqueous phase, has been
      studied in aqueous solutions by spectroscopic experiments and theoretical
      calculations. For the dissociation constant of the protonated form in the ground
      state, pKa = 1.61 was obtained from the absorption spectra; for the excited-state
      dissociation constant, pKa* = 2.19 was obtained from the fluorescence spectra.
      These values were closely reproduced by theoretical calculations via a
      thermodynamic cycle (the value of pKa* also by calculations via the Forster
      cycle) using an implicit-explicit solvation model (polarized continuum model +
      addition of a solvent molecule). The theoretical calculations indicated that (i)
      in the ground state, C102 occurs primarily as a hydrogen-bonded water complex,
      with the oxo group as the binding site, (ii) this hydrogen bond becomes stronger
      upon excitation, and (iii) in the ground state, the amino nitrogen atom is the
      protonation site, and in the excited state, the carboxy oxygen atom is the
      protonation site. A comprehensive analysis of fluorescence decay data yielded the
      values kpr = 3.27 * 10(10) M(-1) s(-1) for the rate constant of the excited-state
      protonation and kdpr = 2.78 * 10(8) s(-1) for the rate constant of the reverse
      process (kpr and kdpr were treated as independent parameters). This, considering
      the relatively long fluorescence lifetimes of neutral C102 (6.02 ns) and its
      protonated form (3.06 ns) in aqueous media, means that a quasi-equilibrium state
      of excited-state proton transfer is reached in strongly acidic solutions.

PMID- 24945907
TI  - Determination of multi-class pesticide residue in dietary supplements from grape
      seed extracts by ultra-high-performance liquid chromatography coupled to triple
      quadrupole mass spectrometry.
AB  - A new method was developed and validated for the determination of multi-class
      pesticide residues in nutraceutical products obtained from grape seed extracts.
      The extraction procedure was based on QuEChERS methodology using ethyl acetate as
      solvent and a dispersive solid-phase extraction (dSPE) clean-up stage with C18
      was included to minimise matrix effects. Pesticides determination was achieved
      using ultra-high-performance liquid chromatography coupled to triple quadrupole
      mass spectrometry (UHPLC-QqQ-MS/MS); total running time was 11 min. Pesticides
      were quantified using matrix-matched calibration. The developed method was
      validated in terms of matrix effect, linearity, selectivity, limits of detection
      and quantification, trueness, repeatability and inter-day precision at three
      concentration levels (10, 50, 100 ug kg(-1)). Suitable recovery values were
      obtained for 76% of analysed pesticides at the lowest concentration (10 ug kg(
      1)). For most of the compounds, relative standard deviation values were lower
      than 20% and 25% for intra- and inter-day precision, respectively. Finally, 106
      pesticides were determined, and the method was applied to seven dietary
      supplements from grape seed extract, obtaining various positive results for
      piperonyl butoxide, cyromazine and diniconazole at concentrations ranging from
      2.0 to 13.4 ug kg(-1).

PMID- 24945908
TI  - Synthesis and self-assembly of well-defined elastin-like polypeptide
      poly(ethylene glycol) conjugates.
AB  - A series of stimulus-responsive elastin-like polypeptide-poly(ethylene glycol)
      (ELP-PEG) block copolymers was synthesized. The polymeric building blocks were
      conjugated via the efficient and specific strain-promoted alkyne-azide
      cycloaddition (SPAAC). For this purpose, ELP and PEG blocks were functionalized
      with azide and cyclooctyne moieties, respectively. Azides were introduced by
      applying a recently developed pH-controlled diazotransfer reaction on the primary
      amines present in ELP (N-terminus and lysine side chains). By varying pH, ELP
      blocks with one or two azides were obtained, which subsequently allowed us to
      synthesize both ELP-PEG diblock copolymers and miktoarm star polymers. Triggering
      the phase transition of the ELP-block resulted in the formation of an amphiphilic
      block copolymer, which self-assembled into micelles. This is the first example of
      an ELP-containing hybrid block copolymer in which PEG as the hydrophilic corona
      forming domain is combined with a stimulus-responsive ELP-block. The
      encapsulation of a hydrophobic fluorescent dye was shown to exemplify the
      potential of the micelles to serve as nanocarriers for hydrophobic drugs, with
      the PEG corona providing stealth and steric protection of encapsulated materials.

PMID- 24945911
TI  - Timothy Perper, PhD (1939-2014).

PMID- 24945910
TI  - Dominance effects of deleterious and beneficial mutations in a single gene of the
      RNA virus phi6.
AB  - Most of our knowledge of dominance stems from studies of deleterious mutations.
      From these studies we know that most deleterious mutations are recessive, and
      that this recessivity arises from a hyperbolic relationship between protein
      function (i.e., protein concentration or activity) and fitness. Here we
      investigate whether this knowledge can be used to make predictions about the
      dominance of beneficial and deleterious mutations in a single gene. We employed a
      model system--the bacteriophage phi6--that allowed us to generate a collection of
      mutations in haploid conditions so that it was not biased toward either dominant
      beneficial or recessive deleterious mutations. Screening for the ability to
      infect a bacterial host that does not permit infection by the wildtype phi6, we
      generated a collection of mutations in P3, a gene involved in attachment to the
      host and in phage particle assembly. The resulting collection contained mutations
      with both deleterious and beneficial effects on fitness. The deleterious
      mutations in our collection had additive effects on fitness and the beneficial
      mutations were recessive. Neither of these observations were predicted from
      previous studies of dominance. This pattern is not consistent with the hyperbolic
      (diminishing returns) relationship between protein function and fitness that is
      characteristic of enzymatic genes, but could have resulted from a curve of
      increasing returns.

PMID- 24945909
TI  - Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular
      features of active ulcerative colitis.
AB  - BACKGROUND: The colonic mucus layer plays a critical role in intestinal
      homeostasis by limiting contact between luminal bacteria and the mucosal immune
      system. A defective mucus barrier in animal models allows bacterial contact with
      the intestinal epithelium and results in spontaneous colitis. A defective mucus
      barrier is also a key feature of active ulcerative colitis (UC). Alterations in
      the immune compartment due to intestinal bacterial breach in mice lacking the
      colon mucus barrier have not been characterized and correlated to active UC.
      AIMS: To characterize alterations in the immune compartment due to intestinal
      bacterial breach in Muc2-/- mice, which lack the colon mucus barrier, and
      correlate the findings to active UC. METHODS: Bacterial contact with colon
      epithelium and penetration into colon tissue was examined in Muc2-/- mice and
      colon biopsies from patients with active UC using fluorescence microscopy and
      qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in
      colon from Muc2-/- mice and biopsies from UC patients were quantitated by flow
      cytometry. RESULTS: Inflamed UC patients and Muc2-/- mice had bacteria in contact
      with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans
      and Muc2-/- mice and in the draining lymph nodes of mice. Inflamed Muc2-/- mice
      and UC patients had elevated colon neutrophils, T cells and macrophages while a
      reduced frequency of CD103+ DCs was present in the inflamed colon of both mice
      and humans. CONCLUSIONS: The parallel features of the colon immune cell
      compartment in Muc2-/- mice and UC patients supports the usefulness of this model
      to understand the early phase of spontaneous colitis and will provide insight
      into novel strategies to treat UC.

PMID- 24945912
TI  - Evaluation of anticonvulsant actions of dibromophenyl enaminones using in vitro
      and in vivo seizure models.
AB  - Epilepsy and other seizure disorders are not adequately managed with currently
      available drugs. We recently synthesized a series of dibromophenyl enaminones and
      demonstrated that AK6 and E249 were equipotent to previous analogs but more
      efficacious in suppressing neuronal excitation. Here we examined the actions of
      these lead compounds on in vitro and in vivo seizure models. In vitro seizures
      were induced in the hippocampal slice chemically (zero Mg2+ buffer and
      picrotoxin) and electrically using patterned high frequency stimulation (HFS) of
      afferents. In vivo seizures were induced in rats using the 6 Hz and the maximal
      electroshock models. AK6 (10 uM) and E249 (10 uM) depressed the amplitude of
      population spikes recorded in area CA1 of the hippocampus by -50.5+/-4.3% and 
      40.1+/-3.1% respectively, with partial recovery after washout. In the zero Mg2+
      model, AK6 (10 uM) depressed multiple population spiking (mPS) by -59.3+/-6.9%
      and spontaneous bursts (SBs) by -65.9+/-7.2% and in the picrotoxin-model by 
      43.3+/-7.2% and -50.0+/-8.3%, respectively. Likewise, E249 (10 uM) depressed the
      zero-Mg2+-induced mPS by -48.8+/-9.5% and SBs by -55.8+/-15.5%, and in the
      picrotoxin model by -37.1+/-5.5% and -56.5+/-11.4%, respectively. They both
      suppressed post-HFS induced afterdischarges and SBs. AK6 and E249 dose
      dependently protected rats in maximal electroshock and 6 Hz models of in vivo
      seizures after 30 min pretreatment. Their level of protection in both models was
      similar to that obtained with phenytoin Finally, while AK6 had no effect on
      locomotion in rats, phenytoin significantly decreased locomotion. AK6 and E249,
      suppressed in vitro and in vivo seizures to a similar extent. Their in vivo
      activities are comparable with but not superior to phenytoin. The most
      efficacious, AK6 produced no locomotor suppression while phenytoin did. Thus, AK6
      and E249 may be excellent candidates for further investigation as potential
      agents for the treatment of epilepsy syndromes with possibly less CNS side
      effects. 

PMID- 24945915
TI  - Update on distal deep venous thrombosis. Reports of a multicenter study.
AB  - AIM: No study of strong methodology could be found to resolve the controversy of
      optimal treatment of distal deep venous thrombosis (DDVT). Some inconclusive
      evidence exists on two approaches to care: anticoagulants and compression therapy
      or compression therapy and Duplex scanning monitoring. Different studies report
      propagation to popliteal vein in 8% of patients without anticoagulant treatment,
      while a complete thrombus resolution within 4 weeks occurred in 20% of patients.
      We report data of a study conducted in patients affected by DDVT and treated with
      nadroparin administered once daily in association with compression therapy.
      METHODS: One hundred and ten patients with DDVT of the gastrocnemius or tibial
      veins, assessed by Duplex scanning, were enrolled in 8 clinical centres of the
      Lazio Region. At baseline, patient demographics, medical history (including risk
      factors for DDVT), circumferences of both calves and ankles, and a VAS-pain scale
      were recorded. At 7 and 28 days from baseline, patients were re-assessed by
      Duplex scanning, calves and ankles circumferences and VAS-pain were measured, and
      the patients were asked about possible side effects. RESULTS: At the end of the
      study period, no propagation to the popliteal vein was observed, and no side
      effects were reported. Overall, the calf circumference in the affected leg
      significantly decreased from baseline (38.1 cm) to week 1 (37.1 cm), and to week
      4 (35.7 cm). Also the VAS-pain scores significantly decreased during the study -
      the observed means were 58.4, 30.7, and 12.7 at the three visits, respectively.
      The percentage of partial recanalization of tibial DVT at 7 days was lower than
      gastrocnemius DVT (31.6% vs. 59.8%) whereas the percentage of total
      recanalization at 28 days was comparable (52.6% vs. 59.8%). Complete
      recanalization occurred in 56.4% of all patients. CONCLUSION: Our study suggests
      that anticoagulant treatment, associated with compression therapy, is safe and
      causes clinical improvement (as assessed by calf measurements) and pain relief.
      Overall complete resolution (56.4%) is significantly higher than in untreated
      patients (20%). Such results, together with the already reported higher
      satisfaction of patients for the once-daily administration regimen, should be
      considered as a viable option for the treatment of DDVT.

PMID- 24945916
TI  - Endovenous treatment of incompetent anterior accessory saphenous veins with a
      1540 nm diode laser.
AB  - AIM: Endovenous laser treatment (EVLT) is an accepted form of axial vein ablation
      for symptomatic venous reflux but its role in the treatment of anterior accessory
      saphenous vein (AASV) has not been well characterized. The aim of this paper is
      to show the short-term result of EVLT with a ball-tipped fiber and a 1540 nm
      diode laser of the AASV with preservation of a competent great saphenous vein
      (GSV). METHODS: Nine incompetent AASV veins in 8 patients (6 female) were
      treated. The gravity of chronic venous disease was determined according to the
      CEAP classification and the severity of symptoms was scored according to the
      revised Venous Clinical Severity Score. Patient satisfaction was assessed by a 0
      to 3 scale. RESULTS: The average linear endovenous energy density was 60.5 J/cm
      vein (SD: 7.5). Patients returned to daily activities after a mean of 3.8 days
      (SD: 1.4). 5 patients (63%) have had pain but of mild intensity. No patients
      developed paresthesia or phlebitis reactions in the treated area. Post-operative
      ecchymoses are frequent (89%). During the follow-up period (mean 13 months,
      range: 7-17 months) all the veins were occluded. The VCSS improved drastically
      from a mean of 3.2 (SD: 1.3) preinterventional to 0 (SD: 0.38) at 17 months. All
      patients were satisfied or very satisfied with the method. No severe
      complications occurred. CONCLUSION: EVLT of an incompetent AASV with a 1540 nm
      diode laser is a safe and efficient therapy option, with a high success rate and
      with no evidence of GSV neo-reflux or recurrent varicosities during the follow-up
      period.

PMID- 24945917
TI  - A meta-analysis of the association of obesity with abdominal aortic aneurysm
      presence.
AB  - AIM: The aim of this paper was to determine whether obesity is associated with
      abdominal aortic aneurysm (AAA) presence. We performed the first meta-analysis of
      currently available studies. METHODS: MEDLINE and EMBASE were searched through
      January 2014. Eligible studies were comparative studies comparing body mass index
      (BMI) in patients with AAA to that in subjects without AAA or estimating a
      relative risk of AAA prevalence for subjects with obesity (high BMI). RESULTS: Of
      183 potentially relevant articles screened initially, 19 eligible studies
      enrolling 29,120 patients with AAA and 3,163,575 subjects without AAA were
      identified and included. A pooled analysis demonstrated no statistically
      significant difference between BMI in the AAA group and that in the control
      group: mean difference, 0.46 kg/m2; 95% confidence interval, -0.07 to 1.00 kg/m2;
      P=0.09. Another pooled analysis demonstrated that obesity was unassociated with a
      statistically significant increase in AAA prevalence: odds ratio, 1.07; 95%
      confidence interval, 0.94 to 1.22; P=0.30. There was no evidence of significant
      publication bias: P=0.69 and 0.90 for mean difference and odds ratio,
      respectively. CONCLUSION: Obesity appears to be unassociated with AAA presence.

PMID- 24945914
TI  - A translocated effector required for Bartonella dissemination from derma to blood
      safeguards migratory host cells from damage by co-translocated effectors.
AB  - Numerous bacterial pathogens secrete multiple effectors to modulate host cellular
      functions. These effectors may interfere with each other to efficiently control
      the infection process. Bartonellae are Gram-negative, facultative intracellular
      bacteria using a VirB type IV secretion system to translocate a cocktail of
      Bartonella effector proteins (Beps) into host cells. Based on in vitro infection
      models we demonstrate here that BepE protects infected migratory cells from
      injurious effects triggered by BepC and is required for in vivo dissemination of
      bacteria from the dermal site of inoculation to blood. Human endothelial cells
      (HUVECs) infected with a DeltabepE mutant of B. henselae (Bhe) displayed a cell
      fragmentation phenotype resulting from Bep-dependent disturbance of rear edge
      detachment during migration. A DeltabepCE mutant did not show cell fragmentation,
      indicating that BepC is critical for triggering this deleterious phenotype.
      Complementation of DeltabepE with BepEBhe or its homologues from other Bartonella
      species abolished cell fragmentation. This cyto-protective activity is confined
      to the C-terminal Bartonella intracellular delivery (BID) domain of BepEBhe
      (BID2.EBhe). Ectopic expression of BID2.EBhe impeded the disruption of actin
      stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell
      migration via the RhoA signaling pathway, a major regulator of rear edge
      retraction. An intradermal (i.d.) model for B. tribocorum (Btr) infection in the
      rat reservoir host mimicking the natural route of infection by blood sucking
      arthropods allowed demonstrating a vital role for BepE in bacterial dissemination
      from derma to blood. While the Btr mutant DeltabepDE was abacteremic following
      i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored
      bacteremia. Given that we observed a similar protective effect of BepEBhe on
      infected bone marrow-derived dendritic cells migrating through a monolayer of
      lymphatic endothelial cells we propose that infected dermal dendritic cells may
      be involved in disseminating Bartonella towards the blood stream in a BepE
      dependent manner. 

PMID- 24945918
TI  - Great saphenous vein stripping and nerve injury: the role of stripping direction.
AB  - AIM: Although saphenous nerve (SN) injury represents a complication of great
      saphenous vein (GSV) stripping, little is know about the techniques to minimize
      the risk of nerve injury. This is still controversial if the stripping direction
      could be related to the incidence of nerve injury. METHODS: A prospective
      comparative study to compare upwards and downwards total GSV stripping during
      saphenectomy with regard to the occurrence of postoperative SN injury has been
      designed. Electroneurogram measurement and clinical identification of nerve
      injury have been performed 1 day before surgery, 1 week, 12 weeks and 1 year
      after surgery. RESULTS: Although clinical evaluation of nerve injury was found to
      be similar among upwards and downwards stripping both at one and 12 weeks after
      surgery, ENG measurement showed a higher incidence of lesions after the downwards
      stripping both at one and 12 weeks after surgery. No clinical or ENG findings of
      nerve injury was found 1 year after surgery. CONCLUSION: Upwards method is less
      traumatic than downwards total GSV stripping in terms of incidence of SN injury,
      as confirmed by electrophysiological nerve studies.

PMID- 24945919
TI  - Management and fate of renal arteries during endovascular pararenal and
      thoracoabdominal aneurysm repair.

PMID- 24945920
TI  - A contemporary meta-analysis of the association of diabetes with abdominal aortic
      aneurysm.
AB  - AIM: Aim of the present study was to determine whether diabetes is independently
      and inversely associated with prevalence of abdominal aortic aneurysm (AAA). We
      performed a meta-analysis of contemporary literature in which adjusted (but not
      unadjusted) relative risk estimates are available. METHODS: MEDLINE and EMBASE
      were searched from January 1999 to April 2014 using Web-based search engines
      (PubMed and OVID). Studies considered for inclusion met the following criteria:
      the design was a prospective-cohort, population-screening, or case-control study;
      the study population was individuals with and without diabetes or AAA; and
      outcomes included adjusted (but not unadjusted) relative risks for
      prevalence/incidence of AAA in patients with diabetes versus subjects without
      diabetes. Study-specific adjusted relative risk estimate were combined using
      inverse variance-weighted average of logarithmic odds ratios (or hazard ratios)
      in the random-effects model. RESULTS: Of 324 potentially relevant articles
      screened initially, 13 eligible studies were identified and included. A pooled
      analysis of all the 13 studies demonstrated that diabetes was significantly
      associated with lower prevalence of AAA (odds ratio, 0.59; 95% confidence
      interval, 0.52 to 0.67; P<0.00001). When data from 6 prospective-cohort, 5
      population-screening, and 2 case-control studies were separately pooled, diabetes
      was also significantly associated with lower prevalence of AAA (P for subgroup
      differences =0.05). CONCLUSION: Diabetes appears to be inversely associated with
      prevalence of AAA.

PMID- 24945921
TI  - Inside amber: the structural role of succinic acid in Class Ia and Class Id
      resinite.
AB  - For the first time, molecular evidence of the structural role played by succinic
      acid within the macromolecular structure of Class Ia and Class Id resinite is
      presented. Using a novel gas chromatographic methodology, communol (Class Ia) and
      ozol (Class Id) moieties within the polylabdane matrix are shown to be cross
      linked with succinic acid. Samples were analyzed using pyrolysis-gas
      chromatography-mass spectrometry with in situ hexamethyldisilazane
      derivatization, using a thermal separation probe to perform the pyrolysis and
      sample introduction. The relatively slow rate of heating and prolonged pyrolysis
      of resinites using this new methodology, combined with the use of a mild
      derivatization reagent, allowed communol pyrolysates from Class Ia resinite and
      ozol pyrolysates from Class Id resinite to elute with unbroken succinyl ester
      cross-linkages. These results provide direct molecular evidence that the key role
      of succinic acid within Class Ia and Class Id resinite is to cross-link the
      macromolecular structure. In the Class Id resinite, the methodology also allowed
      the detection of succinyl ester linkages between ozol pyrolysates and
      dehydroabietol, thus demonstrating that nonpolymerized diterpenes contribute
      structurally to the macromolecular structure of Class Id resinite. 

PMID- 24945923
TI  - Cluster nucleation and growth from a highly supersaturated adatom phase: silver
      on magnetite.
AB  - The atomic-scale mechanisms underlying the growth of Ag on the (?2*?2)R45 degrees
      -Fe3O4(001) surface were studied using scanning tunneling microscopy and density
      functional theory based calculations. For coverages up to 0.5 ML, Ag adatoms
      populate the surface exclusively; agglomeration into nanoparticles occurs only
      with the lifting of the reconstruction at 720 K. Above 0.5 ML, Ag clusters
      nucleate spontaneously and grow at the expense of the surrounding material with
      mild annealing. This unusual behavior results from a kinetic barrier associated
      with the (?2*?2)R45 degrees  reconstruction, which prevents adatoms from
      transitioning to the thermodynamically favorable 3D phase. The barrier is
      identified as the large separation between stable adsorption sites, which
      prevents homogeneous cluster nucleation and the instability of the Ag dimer
      against decay to two adatoms. Since the system is dominated by kinetics as long
      as the (?2*?2)R45 degrees  reconstruction exists, the growth is not well
      described by the traditional growth modes. It can be understood, however, as the
      result of supersaturation within an adsorption template system. 

PMID- 24945922
TI  - Dopaminergic-like neurons derived from oral mucosa stem cells by developmental
      cues improve symptoms in the hemi-parkinsonian rat model.
AB  - Achieving safe and readily accessible sources for cell replacement therapy in
      Parkinson's disease (PD) is still a challenging unresolved issue. Recently, a
      primitive neural crest stem cell population (hOMSC) was isolated from the adult
      human oral mucosa and characterized in vitro and in vivo. In this study we
      assessed hOMSC ability to differentiate into dopamine-secreting cells with a
      neuronal-dopaminergic phenotype in vitro in response to dopaminergic
      developmental cues and tested their therapeutic potential in the hemi
      Parkinsonian rat model. We found that hOMSC express constitutively a repertoire
      of neuronal and dopaminergic markers and pivotal transcription factors. Soluble
      developmental factors induced a reproducible neuronal-like morphology in the
      majority of hOMSC, downregulated stem cells markers, upregulated the expression
      of the neuronal and dopaminergic markers that resulted in dopamine release
      capabilities. Transplantation of these dopaminergic-induced hOMSC into the
      striatum of hemi-Parkinsonian rats improved their behavioral deficits as
      determined by amphetamine-induced rotational behavior, motor asymmetry and motor
      coordination tests. Human TH expressing cells and increased levels of dopamine in
      the transplanted hemispheres were observed 10 weeks after transplantation. These
      results demonstrate for the first time that soluble factors involved in the
      development of DA neurons, induced a DA phenotype in hOMSC in vitro that
      significantly improved the motor function of hemiparkinsonian rats. Based on
      their neural-related origin, their niche accessibility by minimal-invasive
      procedures and their propensity for DA differentiation, hOMSC emerge as an
      attractive tool for autologous cell replacement therapy in PD. 

PMID- 24945924
TI  - Neonatal glucocorticoid treatment increased depression-like behaviour in adult
      rats.
AB  - Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic
      agent to lessen the morbidity of chronic lung disease in premature infants.
      Previous studies suggested that neonatal DEX treatment altered brain development
      and cognitive function. It has been recognized that the amygdala is involved in
      emotional processes and also a critical site of neuronal plasticity for fear
      conditioning. Little is known about the possible long-term adverse effect of
      neonatal DEX treatment on amygdala function. The present study was aimed to
      evaluate the possible effect of neonatal DEX treatment on the synaptic function
      of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous
      tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one
      to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST)
      and electrophysiological recording aged eight weeks. The results of the FST
      showed neonatal DEX treatment increased depression-like behaviour in adulthood.
      After acute stress evoking, the percentage of time spent free floating is
      significantly increased in the DEX treated group compared with the control
      animals. Furthermore, neonatal DEX treatment elevated long-term potentiation
      (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of
      amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059,
      showed significant rescue effects including reduced depression-like behaviour and
      restoration of LTP to within normal range. In conclusion, our results suggested
      that MAPK signalling cascade in the LA plays an important role in the adverse
      effect of neonatal DEX treatment on amygdala function, which may result in
      adverse consequences in adult age, such as the enhancement of susceptibility for
      a depressive disorder in later life.

PMID- 24945928
TI  - Reducing occurrence of Giardia duodenalis in children living in semiarid regions:
      impact of a large scale rainwater harvesting initiative.
AB  - BACKGROUND: In Brazil, about two million people living in rural semiarid regions
      were benefited with the construction of rainwater cement cisterns, as an
      initiative from the program "One Million Cisterns" (P1MC). Nevertheless, few
      epidemiological studies have been conducted to assess health risks or protection
      effects associated with consumption of this water source. The aim of this study
      was to evaluate whether access to rainwater harvesting cisterns is associated
      with the decrease in the occurrence of Giardia duodenalis infections in children,
      compared to other children living in households supplied by other water sources.
      METHODOLOGY/PRINCIPAL FINDINGS: A quasi-experimental study with two concurrent
      cohorts was developed in two rural municipalities of the semiarid region of
      Brazil. A sample of 664 children, aged between 4 months and 5 years old, was
      followed up, of which 332 had access to rainwater cisterns (cistern group) and
      332 did not, having water supplied from alternative sources (comparison group).
      In a period of approximately one year (2010) intestinal parasites were
      investigated in feces three times. The prevalence of G. duodenalis in children
      from the cistern group ranged from 4.8 to 10.5%, while the prevalence in the
      comparison group ranged from 7.6 to 16.7%. Multivariate analysis (GEE) showed a
      higher risk of G. duodenalis infection in children who did not have access to
      rainwater cisterns, when compared to children who did (OR 1.72; 95% CI 1.14
      2.59). The other variables associated with G. duodenalis infection were: number
      of rooms per house (OR 0.89; 95% CI 0.80-0.99); family income (OR0.48; 95% CI
      0.26-0.88); birth order (OR 1.72; 95% CI 1.17-2.51); preterm children (OR 1.70;
      95% CI 1.19-2.43); and improper hand hygiene prior to food preparation (OR 4.78;
      95% CI 1.95-11.76). CONCLUSIONS/SIGNIFICANCE: Ownership of a rainwater cistern is
      associated with a lower prevalence of G. duodenalis infection in children after
      adjustment for environmental and family-related factors. Nevertheless, the study
      suggests the necessity to complement physical interventions with actions related
      to personal and domestic hygiene to enable further reductions in parasite
      infections affecting mainly the underprivileged populations.

PMID- 24945929
TI  - Ultrastructure and molecular phylogenetic position of Neometanema parovale sp.
      nov. (Neometanema gen. nov.), a Marine phagotrophic euglenid with skidding
      motility.
AB  - Heteronema is a commonly encountered genus of phagotrophic euglenids that
      contains very different morphotypes, including elongate gliding species and ovoid
      skidding forms. We report the first ultrastructural and sequence data from a
      culture of an ovoid skidding heteronemid, KM051. Cells were 8-23.5 MUm long with
      22 pellicular strips and a fibrous extracellular layer. The tubular extrusomes
      had dense centre sections. The feeding apparatus was barely visible by light
      microscopy, but included two microtubule-supported rods. The flagella had hollow,
      inflated transition zones, heteromorphic paraxonemal rods, and sheaths of
      flagellar hairs. The posterior flagellum bore a knob that, unusually, sat >2 MUm
      distal to the flagellar base. No ultrastructural features were uniquely shared by
      KM051 and the elongate, gliding species Heteronema scaphurum. Conversely, the
      pellicular microtubule array resembles that in deep-branching primary osmotrophs
      (Aphagea). 18S ribosomal DNA (18S rDNA) phylogenies showed that KM051 is related
      to a recently obtained Heteronema c.f. exaratum sequence. These skidding
      heteronemids are not closely related to H. scaphurum, and instead are closely
      related to Dinema, Anisonema and specifically, Aphagea. The skidding species in
      Heteronema are transferred to Neometanema gen. nov. (along with most species of
      Metanema Klebs, 1893), with KM051 described as Neometanema parovale sp. nov.

PMID- 24945926
TI  - Translational regulation of specific mRNAs controls feedback inhibition and
      survival during macrophage activation.
AB  - For a rapid induction and efficient resolution of the inflammatory response, gene
      expression in cells of the immune system is tightly regulated at the
      transcriptional and post-transcriptional level. The control of mRNA translation
      has emerged as an important determinant of protein levels, yet its role in
      macrophage activation is not well understood. We systematically analyzed the
      contribution of translational regulation to the early phase of the macrophage
      response by polysome fractionation from mouse macrophages stimulated with
      lipopolysaccharide (LPS). Individual mRNAs whose translation is specifically
      regulated during macrophage activation were identified by microarray analysis.
      Stimulation with LPS for 1 h caused translational activation of many feedback
      inhibitors of the inflammatory response including NF-kappaB inhibitors (Nfkbid,
      Nfkbiz, Nr4a1, Ier3), a p38 MAPK antagonist (Dusp1) and post-transcriptional
      suppressors of cytokine expression (Zfp36 and Zc3h12a). Our analysis showed that
      their translation is repressed in resting and de-repressed in activated
      macrophages. Quantification of mRNA levels at a high temporal resolution by
      RNASeq allowed us to define groups with different expression patterns. Thereby,
      we were able to distinguish mRNAs whose translation is actively regulated from
      mRNAs whose polysomal shifts are due to changes in mRNA levels. Active up
      regulation of translation was associated with a higher content in AU-rich
      elements (AREs). For one example, Ier3 mRNA, we show that repression in resting
      cells as well as de-repression after stimulation depends on the ARE. Bone-marrow
      derived macrophages from Ier3 knockout mice showed reduced survival upon
      activation, indicating that IER3 induction protects macrophages from LPS-induced
      cell death. Taken together, our analysis reveals that translational control
      during macrophage activation is important for cellular survival as well as the
      expression of anti-inflammatory feedback inhibitors that promote the resolution
      of inflammation. 

PMID- 24945927
TI  - The effects of theta precession on spatial learning and simplicial complex
      dynamics in a topological model of the hippocampal spatial map.
AB  - Learning arises through the activity of large ensembles of cells, yet most of the
      data neuroscientists accumulate is at the level of individual neurons; we need
      models that can bridge this gap. We have taken spatial learning as our starting
      point, computationally modeling the activity of place cells using methods derived
      from algebraic topology, especially persistent homology. We previously showed
      that ensembles of hundreds of place cells could accurately encode topological
      information about different environments ("learn" the space) within certain
      values of place cell firing rate, place field size, and cell population; we
      called this parameter space the learning region. Here we advance the model both
      technically and conceptually. To make the model more physiological, we explored
      the effects of theta precession on spatial learning in our virtual ensembles.
      Theta precession, which is believed to influence learning and memory, did in fact
      enhance learning in our model, increasing both speed and the size of the learning
      region. Interestingly, theta precession also increased the number of spurious
      loops during simplicial complex formation. We next explored how downstream
      readout neurons might define co-firing by grouping together cells within
      different windows of time and thereby capturing different degrees of temporal
      overlap between spike trains. Our model's optimum coactivity window correlates
      well with experimental data, ranging from ~150-200 msec. We further studied the
      relationship between learning time, window width, and theta precession. Our
      results validate our topological model for spatial learning and open new avenues
      for connecting data at the level of individual neurons to behavioral outcomes at
      the neuronal ensemble level. Finally, we analyzed the dynamics of simplicial
      complex formation and loop transience to propose that the simplicial complex
      provides a useful working description of the spatial learning process. 

PMID- 24945930
TI  - DNA barcoding in amoebozoa and challenges: the example of Cochliopodium.
AB  - The diversity of microbial eukaryotes in general and amoeboid lineages in
      particular is poorly documented. Even though amoeboid lineages are among the most
      abundant microbes, taxonomic progress in the group has been hindered by the
      limitations of traditional taxonomy and technical difficultly in studying them.
      Studies using molecular approaches such as DNA barcoding with cytochrome oxidase
      I (COI) gene are slowly trickling in for Amoebozoa, and they hopefully will aid
      in unveiling the true diversity of the group. In this study a retrospective
      approach is used to test the utility of COI gene in a scale-bearing amoeba,
      Cochliopodium, which is morphologically well defined. A total of 126 COI
      sequences and 62 unique haplotypes were generated from 9 Cochliopodium species.
      Extensive analyses exploring effects of sequence evolution models and length of
      sequence on genetic diversity computations were conducted. The findings show that
      COI is a promising marker for Cochliopodium, except in one case where it failed
      to delineate two morphologically well-defined cochliopodiums. Two species
      delimitation approaches also recognize 8 genetic lineages out of 9 species
      examined. The taxonomic implications of these findings and factors that may
      confound COI as a barcode marker in Cochliopodium and other amoebae are
      discussed.

PMID- 24945931
TI  - A conserved type IV pilin signal peptide H-domain is critical for the post
      translational regulation of flagella-dependent motility.
AB  - In many bacteria and archaea, type IV pili facilitate surface adhesion, the
      initial step in biofilm formation. Haloferax volcanii has a specific set of
      adhesion pilins (PilA1-A6) that, although diverse, contain an absolutely
      conserved signal peptide hydrophobic (H) domain. Data presented here demonstrate
      that these pilins (PilA1-A6) also play an important role in regulating flagella
      dependent motility, which allows cells to rapidly transition between planktonic
      and sessile states. Cells lacking adhesion pilins exhibit a severe motility
      defect, however, expression of any one of the adhesion pilins in trans can rescue
      the motility and adhesion. Conversely, while deleting pilB3-C3, genes required
      for PilA pilus biosynthesis, results in cells lacking pili and having an adhesion
      defect, it does not affect motility, indicating that motility regulation requires
      the presence of pilins, but not assembled pili. Mutagenesis studies revealed that
      the pilin-dependent motility regulatory mechanism does not require the diverse C
      terminal region of the PilA pilins but specifically involves the conserved H
      domain. This novel post-translational regulatory mechanism, which employs
      components that promote biofilm formation to inhibit motility, can provide a
      rapid response to changing environmental conditions. A model for this regulatory
      mechanism, which may also be present in other prokaryotes, is discussed. 

PMID- 24945925
TI  - Systematic phenotyping of a large-scale Candida glabrata deletion collection
      reveals novel antifungal tolerance genes.
AB  - The opportunistic fungal pathogen Candida glabrata is a frequent cause of
      candidiasis, causing infections ranging from superficial to life-threatening
      disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes
      this pathogen a serious clinical threat. To identify novel genes implicated in
      antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion
      library consisting of 619 unique, individually bar-coded mutant strains, each
      lacking one specific gene, all together representing almost 12% of the genome.
      Functional analysis of this library in a series of phenotypic and fitness assays
      identified numerous genes required for growth of C. glabrata under normal or
      specific stress conditions, as well as a number of novel genes involved in
      tolerance to clinically important antifungal drugs such as azoles and
      echinocandins. We identified 38 deletion strains displaying strongly increased
      susceptibility to caspofungin, 28 of which encoding proteins that have not
      previously been linked to echinocandin tolerance. Our results demonstrate the
      potential of the C. glabrata mutant collection as a valuable resource in
      functional genomics studies of this important fungal pathogen of humans, and to
      facilitate the identification of putative novel antifungal drug target and
      virulence genes. 

PMID- 24945932
TI  - The effects of mild or moderate hepatic impairment on the pharmacokinetics,
      safety, and tolerability of naloxegol.
AB  - Naloxegol is a peripherally acting u-opioid receptor antagonist (PAMORA) in
      development for the treatment of opioid-induced constipation (OIC). The
      pharmacokinetics of a single oral 25-mg dose of naloxegol in plasma was assessed
      in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B)
      hepatic impairment and compared with healthy volunteers. Participants were
      matched for sex, age, and body mass index. Hepatically impaired patients
      exhibited a 17%-18% decrease in area under the plasma concentration versus time
      curve (AUC) despite similar maximum plasma concentrations (Cmax ). This was an
      unexpected finding given that naloxegol is primarily cleared by the hepatic
      route. Time to Cmax was shorter in patients with moderate impairment (0.6 hours)
      versus those with mild impairment (2.3 hours) or normal subjects (2.0 hours).
      Mean apparent terminal half-life (t1/2 ) was shorter in patients with mild (9.6
      hours) and moderate (7.5 hours) hepatic impairment versus healthy subjects (11.3
      hours). Reductions in enterohepatic recycling of naloxegol because of hepatic
      impairment may explain the observed decreases in AUC and t1/2 observed in these
      patients. Naloxegol was generally well tolerated, and mild or moderate hepatic
      impairment appeared to have minimal effect on its pharmacokinetics and safety. 

PMID- 24945935
TI  - Endoscopic forehead approach for minimally invasive benign tumor excisions.
AB  - IMPORTANCE: Direct transcutaneous resection has been a widely accepted standard
      for the removal of benign forehead lesions. In recent years, the endoscopic
      approach has become more prevalent because of its noninvasiveness. To date, only
      a few studies with limited case numbers have reported on this technique. We
      report our findings from one of the largest cohorts of patients undergoing tumor
      resection of the forehead via the endoscopic approach. OBJECTIVES: To evaluate
      results of the endoscopic forehead approach for benign tumor excisions, to give a
      more nuanced insight into this procedure, and to discuss technical pearls and
      potential pitfalls from our experience. DESIGN, SETTING, AND PARTICIPANTS:
      Multicenter, retrospective case study at 2 university centers and 1 private
      practice among 36 patients aged 18 to 72 years (mean age, 44 years) who underwent
      the endoscopic forehead approach for benign tumor resections. MAIN OUTCOMES AND
      MEASURES: Symptoms at presentation, surgical procedure and duration, type of
      lesions, intraoperative and postoperative complications, recurrences, and patient
      satisfaction. RESULTS: In total, 34 patients had an asymptomatic forehead mass,
      while 2 patients reported discomfort and headache. Among all patients, complete
      tumor excision was achieved endoscopically. The mean operative time was 36
      minutes. Histopathological examination revealed 18 lipomas, 13 osteomas, 2
      dermoid cysts, and 1 bone fragment after previous rhinoplasty. In 2 patients, no
      specimen was submitted. No hematomas, infections, scalp numbness, contour
      irregularities, temporal branch paralysis, or tumor recurrences occurred. One
      patient had a prolonged area of alopecia, which resolved on its own. All patients
      attested to a high satisfaction rate. CONCLUSIONS AND RELEVANCE: The endoscopic
      approach offers excellent aesthetic results and allows for safe tumor removal. It
      has proven to be an effective and minimally invasive alternative to the
      conventional open approach. LEVEL OF EVIDENCE: 4.

PMID- 24945936
TI  - Stress analysis of a complete maxillary denture under various drop impact
      conditions: a 3D finite element study.
AB  - Complete maxillary dentures are one of the most economic and easy ways of
      treatment for edentulous patients and are still widely used. However, their
      survival rate is slightly above three years. It is presumed that the failure
      reasons are not only due to normal fatigue but also emerge from damage based on
      unavoidable improper usage. Failure types other than long-term fatigue, such as
      over-deforming, also influence the effective life span of dentures. A hypothesis
      is presumed, stating that the premature/unexpected failures may be initiated by
      impact on dentures, which can be related to dropping them on the ground or other
      effects such as biting crispy food. Thus, the behavior of a complete maxillary
      denture under impact loading due to drop on a rigid surface was investigated
      using the finite element method utilizing explicit time integration and a rate
      sensitive elastoplastic material model of polymethylmethacrylate (PMMA). Local
      permanent deformations have been observed along with an emphasis on frenulum
      region of the denture, regardless of the point of impact. Contact stresses at the
      tooth-denture base were also investigated. The spread of energy within the
      structure via wave propagation is seen to play a critical role in this fact.
      Stress-wave propagation is also seen to be an important factor that decreases the
      denture's fatigue life. 

PMID- 24945934
TI  - Colonic immune suppression, barrier dysfunction, and dysbiosis by
      gastrointestinal bacillus anthracis Infection.
AB  - Gastrointestinal (GI) anthrax results from the ingestion of Bacillus anthracis.
      Herein, we investigated the pathogenesis of GI anthrax in animals orally infected
      with toxigenic non-encapsulated B. anthracis Sterne strain (pXO1+ pXO2-) spores
      that resulted in rapid animal death. B. anthracis Sterne induced significant
      breakdown of intestinal barrier function and led to gut dysbiosis, resulting in
      systemic dissemination of not only B. anthracis, but also of commensals. Disease
      progression significantly correlated with the deterioration of innate and T cell
      functions. Our studies provide critical immunologic and physiologic insights into
      the pathogenesis of GI anthrax infection, whereupon cleavage of mitogen-activated
      protein kinases (MAPKs) in immune cells may play a central role in promoting
      dysfunctional immune responses against this deadly pathogen. 

PMID- 24945933
TI  - Cell cycle modulation by Marek's disease virus: the tegument protein VP22
      triggers S-phase arrest and DNA damage in proliferating cells.
AB  - Marek's disease is one of the most common viral diseases of poultry affecting
      chicken flocks worldwide. The disease is caused by an alphaherpesvirus, the
      Marek's disease virus (MDV), and is characterized by the rapid onset of
      multifocal aggressive T-cell lymphoma in the chicken host. Although several viral
      oncogenes have been identified, the detailed mechanisms underlying MDV-induced
      lymphomagenesis are still poorly understood. Many viruses modulate cell cycle
      progression to enhance their replication and persistence in the host cell, in the
      case of some oncogenic viruses ultimately leading to cellular transformation and
      oncogenesis. In the present study, we found that MDV, like other viruses, is able
      to subvert the cell cycle progression by triggering the proliferation of low
      proliferating chicken cells and a subsequent delay of the cell cycle progression
      into S-phase. We further identified the tegument protein VP22 (pUL49) as a major
      MDV-encoded cell cycle regulator, as its vector-driven overexpression in cells
      lead to a dramatic cell cycle arrest in S-phase. This striking functional feature
      of VP22 appears to depend on its ability to associate with histones in the
      nucleus. Finally, we established that VP22 expression triggers the induction of
      massive and severe DNA damages in cells, which might cause the observed intra S
      phase arrest. Taken together, our results provide the first evidence for a
      hitherto unknown function of the VP22 tegument protein in herpesviral
      reprogramming of the cell cycle of the host cell and its potential implication in
      the generation of DNA damages. 

PMID- 24945937
TI  - An improved nonparametric lower bound of species richness via a modified good
      turing frequency formula.
AB  - It is difficult to accurately estimate species richness if there are many almost
      undetectable species in a hyper-diverse community. Practically, an accurate lower
      bound for species richness is preferable to an inaccurate point estimator. The
      traditional nonparametric lower bound developed by Chao (1984, Scandinavian
      Journal of Statistics 11, 265-270) for individual-based abundance data uses only
      the information on the rarest species (the numbers of singletons and doubletons)
      to estimate the number of undetected species in samples. Applying a modified Good
      Turing frequency formula, we derive an approximate formula for the first-order
      bias of this traditional lower bound. The approximate bias is estimated by using
      additional information (namely, the numbers of tripletons and quadrupletons).
      This approximate bias can be corrected, and an improved lower bound is thus
      obtained. The proposed lower bound is nonparametric in the sense that it is
      universally valid for any species abundance distribution. A similar type of
      improved lower bound can be derived for incidence data. We test our proposed
      lower bounds on simulated data sets generated from various species abundance
      models. Simulation results show that the proposed lower bounds always reduce bias
      over the traditional lower bounds and improve accuracy (as measured by mean
      squared error) when the heterogeneity of species abundances is relatively high.
      We also apply the proposed new lower bounds to real data for illustration and for
      comparisons with previously developed estimators.

PMID- 24945940
TI  - Bias-enhanced nucleation and growth processes for ultrananocrystalline diamond
      films in Ar/CH4 plasma and their enhanced plasma illumination properties.
AB  - Microstructural evolution of ultrananocrystalline diamond (UNCD) films in the
      bias-enhanced nucleation and growth (BEN-BEG) process in CH4/Ar plasma is
      systematically investigated. The BEN-BEG UNCD films possess higher growth rate
      and better electron field emission (EFE) and plasma illumination (PI) properties
      than those of the films grown without bias. Transmission electron microscopy
      investigation reveals that the diamond grains are formed at the beginning of
      growth for films grown by applying the bias voltage, whereas the amorphous carbon
      forms first and needs more than 30 min for the formation of diamond grains for
      the films grown without bias. Moreover, the application of bias voltage
      stimulates the formation of the nanographite phases in the grain boundaries of
      the UNCD films such that the electrons can be transported easily along the
      graphite phases to the emitting surface, resulting in superior EFE properties and
      thus leading to better PI behavior. Interestingly, the 10 min grown UNCD films
      under bias offer the lowest turn-on field of 4.2 V/MUm with the highest EFE
      current density of 2.6 mA/cm(2) at an applied field of 7.85 V/MUm. Such superior
      EFE properties attained for 10 min bias grown UNCD films leads to better plasma
      illumination (PI) properties, i.e., they show the smallest threshold field of
      3300 V/cm with largest PI current density of 2.10 mA/cm(2) at an applied field of
      5750 V/cm. 

PMID- 24945939
TI  - Acceleration of aneurysm healing by P(DLLA-co-TMC)-coated coils enabling the
      controlled release of vascular endothelial growth factor.
AB  - Since the introduction of the detachable coil in endovascular treatment of
      intracranial aneurysms, the in-hospital mortality rate has been significantly
      decreased. Recurrence of the aneurysm remains the major drawback of using
      detachable coils. We prepared a bioactive coil coated with poly(d,l-lactide)-7co
      (1,3-trimethylene carbonate) (P(DLLA-co-TMC)), a novel copolymer for controlling
      the release of vascular endothelial growth factor (VEGF). Platinum coils were
      prepared by successive coating with cationic P(DLLA-co-TMC) and anionic heparin.
      Then, recombinant human VEGF-165 (rhVEGF) was immobilized by affinity binding to
      heparin. The morphological characteristics and sustained in vitro release of
      rhVEGF were examined using scanning electron microscopy and enzyme-linked
      immunosorbent assay, respectively. The efficacy of these novel coils modified by
      P(DLLA-co-TMC)/rhVEGF was tested using a common carotid artery aneurysm model in
      rats. Experimental aneurysms were embolized with unmodified, P(DLLA-co
      TMC)/heparin-coated or P(DLLA-co-TMC)/rhVEGF-coated platinum coils (n = 18). The
      coils were removed on days 15, 30 and 90 after insertion, and the histological
      and immunohistochemical analysis of factor VIII was performed to confirm the
      presence of endothelial cells in the organized area. In addition, the controlled
      in vivo release of VEGF was confirmed by Western blotting analysis. The release
      of VEGF tended to increase during the whole period and no burst release was
      observed. In the group treated with P(DLLA-co-TMC)/rhVEGF-coated platinum coils,
      clot organization and endothelial cell proliferation were accelerated. The
      immunohistochemistry study showed that the expression of factor VIII was found in
      the P(DLLA-co-TMC)/rhVEGF-coated coil group but not in the other two groups.
      Furthermore, Western blotting analysis confirmed that the major released VEGF in
      the aneurysm sac was from the P(DLLA-co-TMC)/VEGF-coated coil. P(DLLA-co
      TMC)/rhVEGF-coated platinum coils can promote clot organization and endothelial
      cell proliferation in a rat aneurysm model. 

PMID- 24945941
TI  - Factors influencing the levels of exhaled carbon monoxide in asthmatic children.
AB  - OBJECTIVE: Bronchial asthma is characterised by chronic airway inflammation
      commonly associated with increased oxidative stress. Exhaled carbon monoxide
      (eCO) levels could act as markers of both oxidative stress and allergic
      inflammation. We aimed to study eCO levels in asthmatics and detect the possible
      factors influencing them. METHODS: We studied 241 asthmatic children and 75
      healthy children. The differences in eCO levels among various asthmatic
      phenotypes and the correlations between eCO and other measured parameters
      (spirometric indices, Asthma Control Test score, exhaled nitric oxide, total IgE,
      blood eosinophils and marker of oxidative damage of proteins) were analysed.
      RESULTS: Levels of eCO widely differed according to the selected characteristics
      of asthma. Asthmatics showed higher eCO concentrations than controls (1.44 +/-
      0.12 ppm vs. 0.91 +/- 0.11 ppm, p < 0.001). Acute exacerbation of asthma was
      accompanied by a significant increase in eCO compared to the clinically
      controlled stage (2.17 +/- 0.36 ppm vs. 1.33 +/- 0.13 ppm, p < 0.001). Atopic,
      non-atopic asthma and asthma associated with allergic rhinitis (AR) showed
      elevated levels of eCO. The levels of eCO negatively correlated with the marker
      of protein oxidation in asthmatics, especially in atopic form and during acute
      exacerbation. CONCLUSIONS: In a population of asthmatic children, eCO levels
      could be considered as a marker of both allergic inflammation and oxidative
      stress in the airways. Concomitant AR and asthma control were the most important
      factors affecting the levels of eCO in asthmatic children. However, our results
      do not support the use of routine eCO in the clinical practice.

PMID- 24945942
TI  - Blood gas tensions in adult asthma: a systematic review and meta-regression
      analysis.
AB  - OBJECTIVE: The last half-century has seen substantial changes in asthma treatment
      and care. We investigated whether arterial blood gas parameters in acute and non
      acute asthma have changed historically. METHODS: We performed a systematic search
      of the literature for studies reporting P(aO2) , P(aCO2) and forced expiratory
      volume in 1 s, percentage of predicted (FEV1%). For each of the blood gas
      parameters, meta-regression analyses examined its association with four
      background variables: the publication year, mean FEV1%, mean age and female
      fraction in the respective studies. RESULTS: After screening, we included 43
      articles comprising 61 datasets published between 1967 and 2013. In studies of
      habitual-state asthma, mean P(aO2) was positively associated with the publication
      year (p = 0.001) and negatively with mean age (p < 0.01). Mean P(aCO2) showed a
      positive association with publication year (p = 0.001) and a negative association
      with female fraction (p < 0.05). In acute asthma studies, blood gas levels were
      unassociated with publication year and mean age, mean P(aO2) was positively
      associated with FEV1% (p < 0.05) whereas mean P(aCO2) showed a negative
      association with FEV1% (p < 0.05) for studies with mean FEV1% <40. In neither
      acute nor habitual-state studies was mean arterial pH associated with any of the
      predictor variables. CONCLUSIONS: In studies of habitual-state asthma, mean
      reported P(aO2) and P(aCO2) levels were found to have increased since 1967. In
      acute asthma studies, mean P(aO2) and P(aCO2) were associated with mean FEV1% but
      not with either publication year or patient age.

PMID- 24945938
TI  - Glycosylation inhibitors efficiently inhibit P-selectin-mediated cell adhesion to
      endothelial cells.
AB  - Adhesion molecules play a critical role in the adhesive interactions of multiple
      cell types in sickle cell disease (SCD). We previously showed that anti-P
      selectin aptamer efficiently inhibits cell adhesion to endothelial cells (ECs)
      and permits SCD mice to survive hypoxic stress. In an effort to discover new
      mechanisms with which to inhibit P-selectin, we examined the role of
      glycosylation. P-selectin is a 90 kDa protein but was found to migrate as 90 and
      140 kDa bands on gel electrophoresis. When P-selectin isolated from ECs was
      digested with peptide N-glycosidase F, but not O-glycosidase, the 140 kDa band
      was lost and the 90 kDa band was enhanced. Treatment of ECs with tunicamycin, an
      N-glycosylation inhibitor, suppressed CD62P (P-selectin) expression on the cell
      surface as well as the 140 kDa form in the cytoplasm. These results indicate that
      the 140 kDa band is N-glycosylated and glycosylation is critical for cell surface
      expression of P-selectin in ECs. Thrombin, which stimulates P-selectin expression
      on ECs, induced AKT phosphorylation, whereas tunicamycin inhibited AKT
      phosphorylation, suggesting that AKT signaling is involved in the tunicamycin
      mediated inhibition of P-selectin expression. Importantly, the adhesion of sickle
      red blood cells (sRBCs) and leukocytes to ECs induced by thrombin or hypoxia was
      markedly inhibited by two structurally distinct glycosylation inhibitors; the
      levels of which were comparable to that of a P-selectin monoclonal antibody which
      most strongly inhibited cell adhesion in vivo. Knockdown studies of P-selectin
      using short-hairpin RNAs in ECs suppressed sRBC adhesion, indicating a legitimate
      role for P-selectin in sRBC adhesion. Together, these results demonstrate that P
      selectin expression on ECs is regulated in part by glycosylation mechanisms and
      that glycosylation inhibitors efficiently reduce the adhesion of sRBCs and
      leukocytes to ECs. Glycosylation inhibitors may lead to a novel therapy which
      inhibits cell adhesion in SCD. 

PMID- 24945943
TI  - The role of the hydrophobic phase in the unique rheological properties of saponin
      adsorption layers.
AB  - Saponins are a diverse class of natural, plant derived surfactants, with peculiar
      molecular structure consisting of a hydrophobic scaffold and one or several
      hydrophilic oligosaccharide chains. Saponins have strong surface activity and are
      used as natural emulsifiers and foaming agents in food and beverage,
      pharmaceutical, ore processing, and other industries. Many saponins form
      adsorption layers at the air-water interface with extremely high surface
      elasticity and viscosity. The molecular origin of the observed unique interfacial
      visco-elasticity of saponin adsorption layers is of great interest from both
      scientific and application viewpoints. In the current study we demonstrate that
      the hydrophobic phase in contact with water has a very strong effect on the
      interfacial properties of saponins and that the interfacial elasticity and
      viscosity of the saponin adsorption layers decrease in the order: air >
      hexadecane ? tricaprylin. The molecular mechanisms behind these trends are
      analyzed and discussed in the context of the general structure of the surfactant
      adsorption layers at various nonpolar phase-water interfaces. 

PMID- 24945944
TI  - An operon of three transcriptional regulators controls horizontal gene transfer
      of the integrative and conjugative element ICEclc in Pseudomonas knackmussii B13.
AB  - The integrative and conjugative element ICEclc is a mobile genetic element in
      Pseudomonas knackmussii B13, and an experimental model for a widely distributed
      group of elements in Proteobacteria. ICEclc is transferred from specialized
      transfer competent cells, which arise at a frequency of 3-5% in a population at
      stationary phase. Very little is known about the different factors that control
      the transfer frequency of this ICE family. Here we report the discovery of a
      three-gene operon encoded by ICEclc, which exerts global control on transfer
      initiation. The operon consists of three consecutive regulatory genes, encoding a
      TetR-type repressor MfsR, a MarR-type regulator and a LysR-type activator TciR.
      We show that MfsR autoregulates expression of the operon, whereas TciR is a
      global activator of ICEclc gene expression, but no clear role was yet found for
      MarR. Deletion of mfsR increases expression of tciR and marR, causing the
      proportion of transfer competent cells to reach almost 100% and transfer
      frequencies to approach 1 per donor. mfsR deletion also caused a two orders of
      magnitude loss in population viability, individual cell growth arrest and loss of
      ICEclc. This indicates that autoregulation is an important feature maintaining
      ICE transfer but avoiding fitness loss. Bioinformatic analysis showed that the
      mfsR-marR-tciR operon is unique for ICEclc and a few highly related ICE, whereas
      tciR orthologues occur more widely in a large variety of suspected ICE among
      Proteobacteria. 

PMID- 24945945
TI  - Circulating autoantibodies to endothelial progenitor cells: binding
      characteristics and association with risk factors for atherosclerosis.
AB  - OBJECTIVE: Endothelial progenitor cells (EPC) are committed to transform into EC
      promoting vasculogenic ischemic repair. Anti-endothelial cells (AECA) have been
      described in various disorders with an associated vascular damage. Herein, we
      explored a novel circulating population of IgG reactive with EPC, in patients
      with differential risk profile for atherosclerotic vascular disease. APPROACH AND
      RESULTS: A novel cyto-ELISA system was established where the coated cells were
      late outgrowth EPC. Levels of anti-EPC antibodies were determined in 100 subjects
      and differential risk score for atherosclerosis, as well as to circulating EPC
      levels and the inflammatory markers IL-6 and C-reactive protein. To study
      endothelial cell (EC) activating properties, sera were tested for their ability
      to induce VCAM-1 expression in a cell ELISA system. Detectable levels of anti-EPC
      antibodies, that correlated with age, Framingham risk score and CRP
      concentrations but did not associate with levels of LDL, HDL, hypertension or
      diabetes, were detected. Anti-EPC antibodies were distinct from EC binding
      antibodies as shown by competitive inhibition studies, and have been positively
      correlated with the extent of EC activation manifested by in vitro VCAM-1
      expression. CONCLUSION: This is the first study showing a newly defined subgroup
      of self-antibodies binding EPC and associating positively with the Framingham
      risk score. Further studies are required to characterize and test this
      interesting subset of EPC binding autoantibodies and their potential
      significance.

PMID- 24945946
TI  - Evaluation of two palate repair techniques for the surgical management of
      velopharyngeal insufficiency.
AB  - BACKGROUND: The Furlow palatoplasty is commonly used for the correction of
      velopharyngeal insufficiency in cleft patients. An alternative procedure is
      introduced involving a single Z-plasty with overlapping intravelar veloplasty
      (Woo palatoplasty). This study compared the results of both techniques in the
      correction of velopharyngeal insufficiency. METHODS: After institutional review
      board approval, a retrospective chart review was performed of all patients who
      had undergone secondary palatoplasty for the correction of velopharyngeal
      insufficiency. All nonsyndromic patients with imaging data were evaluated. Data
      elements included preoperative and postoperative velopharyngeal gap size and
      perceptual speech examination results. RESULTS: Fifty-two subjects were included:
      30 subjects had undergone Furlow palatoplasty and 22 underwent Woo palatoplasty.
      Overall, a larger proportion of Woo (95 percent) than Furlow subjects (63
      percent) did not require secondary surgery (p = 0.005). However, mean presurgery
      closure was significantly different between groups (p = 0.042). For a more
      refined assessment, only those with 80 percent or greater preoperative closure
      were evaluated. Successful results were achieved in 67 percent (10 of 15) in
      Furlow and in 100 percent (19 of 19) in Woo. Again, this finding was significant
      (p = 0.005). Linear regression analysis suggested a significant effect of cleft
      type (beta = 2.3, p = 0.013) on closure after repair, with decreased closure in
      cases with isolated cleft palate. CONCLUSIONS: The Woo palatoplasty compared
      favorably with Furlow palatoplasty for correction of velopharyngeal
      insufficiency. The technique appears to be a viable alternative for palatal re
      repair, especially in circumstances when Furlow palatoplasty cannot be performed.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24945947
TI  - Nonendoscopic deactivation of nerve triggers in migraine headache patients:
      surgical technique and outcomes.
AB  - BACKGROUND: Low efficacy, significant side effects, and refractory patients often
      limit the medical treatment of migraine headache. However, new surgical options
      have emerged. Dr. Bahman Guyuron and others report response rates between 68 and
      95 percent after surgical deactivation of migraine trigger sites in select
      patients. In an effort to replicate and expand migraine trigger-site deactivation
      surgery as a treatment option, the authors' group and others have developed
      nonendoscopic algorithms. The exclusion of endoscopic techniques may be useful
      for surgeons with little experience or limited access to the endoscope and in
      patients with challenging anatomy. METHODS: Forty-three consecutive trigger
      deactivation procedures in 35 patients were performed. Preoperative and 12-month
      postoperative migraine questionnaires and patient charts were reviewed. Response
      to surgery in terms of migraine symptom relief and adverse events were evaluated.
      RESULTS: The overall positive response rate was 90.7 percent. Total elimination
      of migraine headaches was reported in 51.3 percent of those with a positive
      response, greater than 80 percent resolution of symptoms was reported in 20.5
      percent, and 28.2 percent had resolution between 50 and 80 percent. No
      significant effect was reported following 9.3 percent of procedures. There were
      no major adverse events. CONCLUSIONS: Nonendoscopic trigger deactivation is a
      safe and effective treatment in select migraine headache patients. Although
      surgical techniques and understanding of the mechanisms of relief are evolving,
      results continue to be promising. This series confirms that excellent results can
      be attained without the endoscope. The authors continue to study these patients
      prospectively to improve patient selection and refine the protocol. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24945948
TI  - Preemptive analgesia with bupivacaine in reduction mammaplasty: a prospective,
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Preincisional analgesia is an antinociceptive treatment that prevents
      altered central excitability from high-intensity noxious stimuli. To determine
      the analgesic efficacy of preoperative infiltration with bupivacaine for
      reduction mammaplasty, a randomized, double-blind, placebo-controlled trial was
      designed. METHODS: Women with mammary hypertrophy were allocated randomly to one
      of two study groups. Patients in group I received preincision infiltration with
      bupivacaine into each breast after general anesthesia. Group II patients received
      similar injections of saline injection alone after general anesthesia. RESULTS:
      Visual analogue pain score, verbal pain score, and short-form McGill Pain
      Questionnaire scores were higher in group II patients until 22 hours after
      surgery (p < 0.008). Patients in the saline group had higher intravenous
      meperidine consumption for 22 hours postoperatively and solicited opioids before
      the patients in the bupivacaine group (p < 0.001). The difference between groups
      was statistically significant. CONCLUSION: Preincisional infiltration with
      bupivacaine results in reduced pain and lower postoperative opioid requirements
      in the early postoperative phase of pain following breast reduction. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

PMID- 24945950
TI  - Secondary reconstructive surgery following major upper extremity replantation.
AB  - BACKGROUND: Little literature currently exists on reconstructive strategies
      following successful upper extremity replantation. The authors hypothesized that
      the type of secondary surgery would vary predictably depending on mechanism and
      amputation level. METHODS: The authors performed a retrospective review of upper
      extremity replantations performed at their institution between 2003 and 2012. The
      mean follow-up period was 3 years. Patient, injury, and surgical demographics, as
      well as replantation survival rates and secondary surgical procedures, were
      recorded. RESULTS: Forty-five upper extremity replantations met inclusion
      criteria and the survival rate was 89 percent (n = 40). In 40 cases of successful
      replantation, the average number of secondary surgical procedures was three per
      patient (range, zero to seven). The most common reconstructive procedures were
      soft-tissue coverage (n = 24), tenolysis (n = 24), free functioning muscle
      transfer (n = 18), and tendon transfer (n = 14). For upper arm replantations,
      soft-tissue coverage was the most common secondary surgery; free functioning
      muscle transfer was the most common for amputations between the elbow and mid
      forearm; tenolysis was the most common secondary procedure performed for
      amputations of the distal forearm to wrist. CONCLUSIONS: Proximal-level
      amputations commonly required soft-tissue coverage. Amputations through the
      proximal forearm and elbow often underwent free functioning muscle transfer, and
      tenolysis was the most common secondary surgery following distal forearm and
      wrist amputations. Secondary surgery could be predicted based on the anatomic
      levels of injury.

PMID- 24945949
TI  - Comparative analysis of processing methods in fat grafting.
AB  - BACKGROUND: Centrifugation is a popular processing method, with an unclear
      mechanism of action. Hypotheses include fat concentration, reduced inflammatory
      response by removal of blood, and concentration of adipose-derived stem cells.
      The authors performed multiple experiments to determine the role of
      centrifugation and compared it with a different processing method (mesh/gauze
      technique). METHODS: Lipoaspirate components were quantified after centrifugation
      at increasing speed to determine concentration efficacy. For comparison, the
      authors quantified the concentration efficacy of mesh/gauze. They also compared
      the number of adipose-derived stem cells isolated by either method. To determine
      the effects of each component, they compared fat alone to fat mixed with various
      spinoff components in a mouse model. They also compared centrifugation to
      mesh/gauze. RESULTS: The adipocyte fraction remains constant above 5000 g,
      whereas 1200 g results in 91 percent concentrated fat. Mesh/gauze also results in
      90 percent concentrated fat. The number of adipose-derived stem cells in 1 g of
      fat was 1603 +/- 2020 and 1857 +/- 1832 in the centrifuge and mesh/gauze groups,
      respectively (p = 0.86). Five "add-back" groups were created: fat plus oil, fat
      plus surgical tumescence, fat plus fresh tumescence, fat plus cell pellets and
      fresh tumescence, and fat plus cell pellets. The fat-only group had better
      retention than the groups mixed with tumescence, regardless of whether it was
      surgical, fresh, or had cell pellets. Oil did not affect grafts. Centrifugation
      at 1200 g was equivalent to mesh/gauze (0.73 +/- 0.12 g and 0.72 +/- 0.13 g,
      respectively). CONCLUSIONS: Centrifugation improves graft retention by
      concentration of the adipocyte fraction. The concentration efficacy of mesh/gauze
      is equivalent to centrifugation at 1200 g, with equivalent in vivo outcomes.

PMID- 24945951
TI  - Facial feminization surgery: the forehead. Surgical techniques and analysis of
      results.
AB  - BACKGROUND: Facial feminization surgery encompasses a series of surgical
      techniques derived from plastic and craniomaxillofacial surgery to soften facial
      features that are generally perceived as being more masculine, mainly in patients
      diagnosed with gender dysphoria. This article describes the main surgical
      techniques used in feminization of the forehead complex, sequences the different
      steps in forehead reconstruction, evaluates results obtained using cephalometric
      analysis, and includes the level of patient satisfaction. METHODS: Between
      January of 2008 and December of 2012, the authors performed a total of 172
      forehead operations. The postsurgical results were analyzed using postoperative
      cephalometric studies that were compared with preoperative teleradiographies. The
      patients' level of satisfaction was also evaluated using a satisfaction
      questionnaire that they filled out after a 6-month postoperative period. RESULTS:
      Along with an evaluation of patient satisfaction and clinical and cephalometric
      results where significant setback of the frontal bossing was observed, the
      authors present the sequencing of frontonasal-orbital reconstruction/recontouring
      with systematic osteotomy of the anterior wall of the frontal sinus in addition
      to developing a modification of the standard coronal approach. CONCLUSIONS: By
      treating the forehead region with the different surgical procedures described in
      this article, masculine facial features of the upper third can be modified with
      predictable and satisfactory results. Facial feminization surgery must be
      considered part of the process of treating patients with gender dysphoria,
      because the modification and elimination of masculine facial features allows
      these patients to adapt more easily to the workplace and social and family
      environments. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24945952
TI  - Application of finite element modeling to optimize flap design with tissue
      expansion.
AB  - BACKGROUND: Tissue expansion is a widely used technique to create skin flaps for
      the correction of sizable defects in reconstructive plastic surgery. Major
      complications following the inset of expanded flaps include breakdown and
      uncontrolled scarring secondary to excessive tissue tension. Although it is
      recognized that mechanical forces may significantly impact the success of defect
      repair with tissue expansion, a mechanical analysis of tissue stresses has not
      previously been attempted. Such analyses have the potential to optimize flap
      design preoperatively. METHODS: The authors establish computer-aided design as a
      tool with which to explore stress profiles for two commonly used flap designs,
      the direct advancement flap and the double back-cut flap. The authors advanced
      both flaps parallel and perpendicular to the relaxed skin tension lines to
      quantify the impact of tissue anisotropy on stress distribution profiles.
      RESULTS: Stress profiles were highly sensitive to flap design and orientation of
      relaxed skin tension lines, with stress minimized when flaps were advanced
      perpendicular to relaxed skin tension lines. Maximum stresses in advancement
      flaps occurred at the distal end of the flap, followed by the base. The double
      back-cut design increased stress at the lateral edges of the flap. CONCLUSIONS:
      The authors conclude that finite element modeling may be used to effectively
      predict areas of increased flap tension. Performed preoperatively, such modeling
      can allow for the optimization of flap design and a potential reduction in
      complications such as flap dehiscence and hypertrophic scarring.

PMID- 24945953
TI  - Long-term outcomes following lower extremity sarcoma resection and reconstruction
      with vascularized fibula flaps in children.
AB  - BACKGROUND: Limb salvage operations in patients with bony oncologic defects carry
      technical challenges and may require long recoveries. This study aimed to
      evaluate functional outcomes, donor-site morbidity, and complications in lower
      limb bony oncologic defects reconstructed with vascularized fibula flaps in
      children. METHODS: The authors performed a retrospective review of consecutive
      pediatric patients undergoing this procedure between 1994 and 2012. Data on
      operative details, functional outcomes, and complications were analyzed. A
      telephone survey was conducted to assess patient satisfaction and quality of
      life. RESULTS: Eighteen patients who underwent 19 reconstructions were included.
      Mean age at resection was 10 years (range, 1.5 to 17 years). No patients
      developed local recurrence, although two patients had metastatic lung nodules
      resected. All patients were alive at last review, with a mean follow-up of 57
      months (range, 10 to 145 months). Flap survival was 95 percent. Median time to
      bony union was 24 months (range, 9 to 72 months). The fibula flap fracture rate
      was 52.6 percent. At the end of the study period, 72 percent of patients were
      fully weight-bearing, all school-age children had returned to full-time school,
      and 50 percent were involved in sports. Fifty-six percent of patients
      participated in the follow-up telephone survey; of these, 90 percent expressed
      satisfaction with the outcome of the surgery. CONCLUSIONS: This study
      demonstrates that the vascularized fibula flap is an excellent option for
      reconstruction of lower limb oncologic defects in children. Despite
      complications, long-term follow-up suggests that most children are able to lead
      active lifestyles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24945954
TI  - Fluorescence anisotropy-based measurement of Pseudomonas aeruginosa penicillin
      binding protein 2 transpeptidase inhibitor acylation rate constants.
AB  - High-molecular-weight penicillin-binding proteins (PBPs) are essential integral
      membrane proteins of the bacterial cytoplasmic membrane responsible for
      biosynthesis of peptidoglycan. They are the targets of antibacterial beta-lactam
      drugs, including penicillins, cephalosporins, and carbapenems. beta-Lactams
      covalently acylate the active sites of the PBP transpeptidase domains. Because
      beta-lactams are time-dependent inhibitors, quantitative assessment of the
      inhibitory activity of these compounds ideally involves measurement of their
      second-order acylation rate constants. We previously described a fluorescence
      anisotropy-based assay to measure these rate constants for soluble constructs of
      PBP3 (Anal. Biochem. 439 (2013) 37-43). Here we report the expression and
      purification of a soluble construct of Pseudomonas aeruginosa PBP2 as a fusion
      protein with NusA. This soluble PBP2 was used to measure second-order acylation
      rate constants with the fluorescence anisotropy assay. Measurements were obtained
      for mecillinam, which reacts specifically with PBP2, and for several carbapenems.
      The assay also revealed that PBP2 slowly hydrolyzed mecillinam and was used to
      measure the rate constant for this deacylation reaction. 

PMID- 24945955
TI  - External mitochondrial NADH-dependent reductase of redox cyclers: VDAC1 or
      Cyb5R3?
AB  - It was reported that VDAC1 possesses an NADH oxidoreductase activity and plays an
      important role in the activation of xenobiotics in the outer mitochondrial
      membrane. In the present work, we evaluated the participation of VDAC1 and Cyb5R3
      in the NADH-dependent activation of various redox cyclers in mitochondria. We
      show that external NADH oxidoreductase caused the redox cycling of menadione ?
      lucigenin>nitrofurantoin. Paraquat was predominantly activated by internal
      mitochondria oxidoreductases. An increase in the ionic strength stimulated and
      suppressed the redox cycling of negatively and positively charged acceptors, as
      was expected for the Cyb5R3-mediated reduction. Antibodies against Cyb5R3 but not
      VDAC substantially inhibited the NADH-related oxidoreductase activities. The
      specific VDAC blockers G3139 and erastin, separately or in combination, in
      concentrations sufficient for the inhibition of substrate transport, exhibited
      minimal effects on the redox cycler-dependent NADH oxidation, ROS generation, and
      reduction of exogenous cytochrome c. In contrast, Cyb5R3 inhibitors (6-propyl-2
      thiouracil, p-chloromercuriobenzoate, quercetin, mersalyl, and ebselen) showed
      similar patterns of inhibition of ROS generation and cytochrome c reduction. The
      analysis of the spectra of the endogenous cytochromes b5 and c in the presence of
      nitrofurantoin and the inhibitors of VDAC and Cyb5R3 demonstrated that the redox
      cycler can transfer electrons from Cyb5R3 to endogenous cytochrome c. This caused
      the oxidation of outer membrane-bound cytochrome b5, which is in redox balance
      with Cyb5R3. The data obtained argue against VDAC1 and in favor of Cyb5R3
      involvement in the activation of redox cyclers in the outer mitochondrial
      membrane. 

PMID- 24945956
TI  - Evidence utilization project: implementation of kangaroo care at neonatal ICU.
AB  - BACKGROUND: Kangaroo care is no longer performed for the initial purpose of
      maintaining a small baby's body temperature in the developed countries where
      there are now sufficient medical equipments to keep babies warm. The objectives
      of kangaroo care in advanced neonatal ICUs have changed to provide benefits such
      as bonding and attachment, physiologic stability of newborn babies, successful
      breastfeeding and positive effects on infant development. Kangaroo care is not
      new to many neonatal nurses, but not every neonatal center is routinely
      practicing kangaroo care in Singapore. Inadequate nurses' knowledge and lack of
      guidelines on kangaroo care hinder its practice. AIM: The aim of this project was
      to implement kangaroo care in very low birth weight babies in a systematic and
      structured approach. METHODS: The team followed Larrabee's The Model For Evidence
      Based Practice Change, used the available evidence on kangaroo care to develop
      guideline that was specific and suitable for the local setting. The team
      organized kangaroo care road shows for nurses and parents to create and enhance
      awareness. Evaluation of the project was done through two audits. The audit tool
      consisted of correct baby positioning and nursing documentation, with a sample
      size of 30 episodes. RESULTS: The ages of the babies audited were from 24 to 34
      weeks of gestation with their weight ranging from 850 to 1500 g. The compliance
      rate for correct baby positioning during kangaroo care was 100% for both audits.
      The compliance rate for nursing documentation improved from 93% in the first post
      implementation audit to 96.7% in the second post-implementation audit.
      CONCLUSION: The systematic and structured approach in kangaroo care
      implementation has created awareness among nurses and led to improvements in
      their knowledge and practices of kangaroo care. The implementation process of
      kangaroo care has also aided in training the ward Evidence-Based Nursing Unit
      team members to engage in critical thinking, which ultimately benefited the
      babies and parents.

PMID- 24945957
TI  - Moving forward towards implementation science.

PMID- 24945958
TI  - Family involvement in decision making for people with dementia in residential
      aged care: a systematic review of quantitative literature.
AB  - AIM: Ensuring older adults' involvement in their care is accepted as good
      practice and is vital, particularly for people with dementia, whose care and
      treatment needs change considerably over the course of the illness. However,
      involving family members in decision making on people's behalf is still
      practically difficult for staff and family. The aim of this review was to
      identify and appraise the existing quantitative evidence about family involvement
      in decision making for people with dementia living in residential aged care.
      METHODS: The present Joanna Briggs Institute (JBI) metasynthesis assessed studies
      that investigated involvement of family members in decision making for people
      with dementia in residential aged care settings. While quantitative and
      qualitative studies were included in the review, this paper presents the
      quantitative findings. A comprehensive search of 15 electronic databases was
      performed. The search was limited to papers published in English, from 1990 to
      2013. Twenty-six studies were identified as being relevant; 10 were quantitative,
      with 1 mixed method study. Two independent reviewers assessed the studies for
      methodological validity and extracted the data using the JBI Meta Analysis of
      Statistics Assessment and Review Instrument (JBI-MAStARI). The findings were
      synthesized and presented in narrative form. RESULTS: The findings related to
      decisions encountered and made by family surrogates, variables associated with
      decisions, surrogates' perceptions of, and preferences for, their roles, as well
      as outcomes for people with dementia and their families. CONCLUSIONS: The results
      identified patterns within, and variables associated with, surrogate decision
      making, all of which highlight the complexity and variation regarding family
      involvement. Attention needs to be paid to supporting family members in decision
      making in collaboration with staff.

PMID- 24945960
TI  - Examining the use of facilitation within guideline dissemination and
      implementation studies in nursing.
AB  - BACKGROUND: Facilitation is a mechanism for implementing practice guidelines in
      nursing. Facilitation aims to prepare clinicians and organisations for
      implementation and to provide support and help in problem-solving as
      implementation progresses. However, any evidence supporting its effectiveness is
      limited due to a lack of empirical testing. AIM: : To examine the presence and
      role of facilitation in studies included in an existing systematic review of
      guideline dissemination and implementation in nursing. METHODS: Using a
      descriptive, exploratory approach, we examined 28 studies for elements of
      facilitation that were included in a review of the effectiveness of interventions
      to increase the use of practice guidelines in nursing. We conducted a content
      analysis of a subset of studies that included facilitation activity to gather
      descriptions of study interventions, characteristics and skills required, use of
      theory, and effectiveness. Extracted data were analysed using a previously
      developed taxonomy containing 53 activities related to facilitation. RESULTS: Ten
      of the 28 studies exhibited evidence of facilitation process and activity. Only
      two of the 10 studies explicitly referred to 'facilitators,' with just one
      indicating that facilitators were a part of the implementation intervention being
      tested. We identified facilitation processes in the eight remaining studies even
      though the authors did not report it as such. All studies used facilitation
      activities in combination with other interventions, the most common being
      educational meetings or distribution of educational materials. We found evidence
      related to facilitation for 37 of the 53 facilitation activities (70%) in the
      taxonomy in at least one study or across studies. An additional three novel
      facilitation-related activities were identified. Most studies exhibited evidence
      of external facilitation activity whereby researchers outside of the setting
      assisted nurses to implement guidelines. Theory informed the development or
      selection of implementation interventions in 60% (n = 6) of the studies. Drawing
      conclusions regarding effectiveness of interventions involving facilitation was
      difficult due to the small number of studies that were included. Furthermore, the
      included studies varied in the detail provided about the intervention or
      combination of interventions tested and how interventions were delivered.
      CONCLUSIONS: Using an existing systematic review for the purpose of gaining
      insight into additional research questions was valuable. Although facilitation
      process and activities are used in interventions to enhance guideline uptake in
      nursing, these were not conceptualized or referred to by researchers as
      'facilitation.' As such, facilitation may be a broader intervention that includes
      organizing and delivering other interventions. Further research is required to
      evaluate the relationship between facilitation and other guideline implementation
      interventions in nursing. The facilitation uncovered within included studies was
      located primarily in the context of research as it was the researchers who
      performed most of the facilitation activities. Future inquiries must explore non
      researcher-initiated and delivered facilitation intervention activities by
      following local groups naturally within clinical contexts.

PMID- 24945959
TI  - A qualitative metasynthesis: family involvement in decision making for people
      with dementia in residential aged care.
AB  - AIM: Involving people in decisions about their care is good practice and ensures
      optimal outcomes. Despite considerable research, in practice family involvement
      in decision making can be challenging for both care staff and families. The aim
      of this review was to identify and appraise existing knowledge about family
      involvement in decision making for people with dementia living in residential
      aged care. METHODS: The present Joanna Briggs Institute meta-synthesis considered
      studies that investigate involvement of family members in decision making for
      people with dementia in residential aged care settings. While quantitative and
      qualitative studies were included in the review, this article presents the
      qualitative findings. A comprehensive search of studies was conducted in 15
      electronic databases. The search was limited to papers published in English, from
      1990 to 2013. Twenty-six studies were identified as relevant for this review; 16
      were qualitative papers reporting on 15 studies. Two independent reviewers
      assessed the studies for methodological validity and extracted the data using the
      standardized Joanna Briggs Institute Qualitative Assessment and Review Instrument
      (JBI-QARI). The findings were synthesized using JBI-QARI. RESULTS: The findings
      related to the decisions encountered and made by family surrogates, family
      perceptions of, and preferences for, their role/s, factors regarding treatment
      decisions and the collaborative decision-making process, and outcomes for family
      decision makers. CONCLUSION: Results indicate varied and complex experiences and
      multiple factors influencing decision making. Communication and contacts between
      staff and families and the support available for families should be addressed, as
      well as the role of different stakeholders in decisions.

PMID- 24945961
TI  - Efficacy of hospital in the home services providing care for patients admitted
      from emergency departments: an integrative review.
AB  - INTRODUCTION: Increases in emergency department (ED) demand may compromise
      patient outcomes, leading not only to overcrowding in the ED, increased ED
      waiting times and increased ED length of stay, but also compromising patient
      safety; the risk of adverse events is known to rise in the presence of
      overcrowding. Hospital in the home (HiTH) services may offer one means of
      reducing ED demand. AIM: This integrative review sought to assess the efficacy of
      admission-avoidance HiTH services that admit patients directly from the ED.
      METHODS: Papers published between 1995 and 2013 were identified through searches
      of Medline, CINAHL and Google. English-language studies that assessed the
      efficacy of a HiTH service and that recruited at least one-third of the
      participants directly from the ED were included in the review. A HiTH service was
      considered one that provided health professional support to patients at home for
      a time-limited period, thus avoiding the need for hospitalization. RESULTS:
      Twenty-two articles met the inclusion criteria for this review. The interventions
      were diverse in terms of the clinical interventions delivered, the range and
      intensity of health professional input and the conditions treated. The studies
      included in the review found no effect on clinical outcomes, rates of adverse
      events or complications, although patient satisfaction and costs were
      consistently and favourably affected by HiTH treatment. CONCLUSION: Given
      evidence suggesting that HiTH services which recruit patients directly from the
      ED contribute to cost-savings, greater patient satisfaction and safety and
      efficacy outcomes that are at least equivalent to those associated with hospital
      based care, the expansion of such programmes might therefore be considered a
      priority for policy makers.

PMID- 24945966
TI  - Influences of agents with a self-reputation awareness component in an
      evolutionary spatial IPD game.
AB  - Iterated prisoner's dilemma (IPD) researchers have shown that strong positive
      reputations plus an efficient reputation evaluation system encourages both sides
      to pursue long-term collaboration and to avoid falling into mutual defection
      cycles. In agent-based environments with reliable reputation rating systems,
      agents interested in maximizing their private interests must show concern for
      other agents as well as their own self-reputations--an important capability that
      standard IPD game agents lack. Here we present a novel learning agent model
      possessing self-reputation awareness. Agents in our proposed model are capable of
      evaluating self-behaviors based on a mix of public and private interest
      considerations, and of testing various solutions aimed at meeting social
      standards. Simulation results indicate multiple outcomes from the addition of a
      small percentage of self-reputation awareness agents: faster cooperation, faster
      movement toward stability in an agent society, a higher level of public interest
      in the agent society, the resolution of common conflicts between public and
      private interests, and a lower potential for rational individual behavior to
      transform into irrational group behavior.

PMID- 24945967
TI  - Ultrasonic nebulization extraction assisted dispersive liquid-liquid
      microextraction followed by gas chromatography for the simultaneous determination
      of six parabens in cosmetic products.
AB  - A simple, rapid, and efficient method of ultrasonic nebulization extraction
      assisted dispersive liquid-liquid microextraction was developed for the
      simultaneous determination of six parabens in cosmetic products. The analysis was
      carried out by gas chromatography. Water was used as the dispersive solvent
      instead of traditional organic disperser. The experimental factors affecting the
      extraction yield, such as the extraction solvent and volume, extraction time,
      dispersive solvent and volume, ionic strength, and centrifuging condition were
      studied and optimized in detail. The limit of detections for the target analytes
      were in the range of 2.0-9.5 MUg/g. Good linear ranges were obtained with the
      coefficients ranging from 0.9934 to 0.9969. The proposed method was successfully
      applied to the analysis of six parabens in 16 cosmetic products. The recoveries
      of the target analytes in real samples ranged from 81.9 to 108.7%, and the
      relative standard deviations were <5.3%. 

PMID- 24945968
TI  - Exogenous expression of OCT4 facilitates oocyte-mediated reprogramming in cloned
      porcine embryos.
AB  - OCT4 is a well-established regulator of pluripotency and nuclear reprogramming.
      To determine if improving OCT4 abundance can facilitate oocyte-mediated
      reprogramming in cloned porcine embryos, we artificially increased OCT4 levels by
      co-incubating donor cells with 50 ng/ul OCT4 plasmid. We observed higher rates of
      blastocyst formation (P < 0.05) and lower levels of blastocyst apoptosis in
      nuclear-transfer-derived embryos carrying OCT4-incubated donor nuclei (OCT4
      SCNT). The beneficial effect caused by exogenous expression of OCT4 involves
      epigenetic changes, wherein increased histone acetylation (AcH3K9) appeared in
      OCT4-SCNT embryos at the one-cell and blastocyst stages and reduced histone
      methylation (H3K9me2) was observed at the one-cell stage (P < 0.05). There was a
      transient increase in exogenous OCT4 and an up-regulation of endogenous OCT4
      level in OCT4-SCNT embryos (P < 0.05), while the expression pattern of epigenetic
      enzymes was changed. These modifications were accompanied by an up-regulation of
      CDX2, whose interaction with OCT4 is instrumental for implantation, and a down
      regulation of XIST, a negative indicator of reprogramming (P < 0.05). Taken
      together, our results support a role for exogenous expression of OCT4 in
      improving the efficiency of nuclear reprogramming while establishing a convenient
      and timesaving method to improve nuclear-transfer outcomes.

PMID- 24945970
TI  - The host model Galleria mellonella is resistant to taylorellae infection.
AB  - The genus Taylorella is composed of two species: (i) Taylorella equigenitalis,
      the causative agent of CEM, a venereally transmitted infection of Equidae and
      (ii) Taylorella asinigenitalis, a closely related species considered to be
      nonpathogenic, although experimental infection of mares with this bacterium
      resulted in clinical signs of vaginitis, cervicitis or endometritis. Currently,
      there is a need for an alternative host model to further study the taylorellae
      species. In this context, we explored Galleria mellonella larvae as potential
      alternative model hosts for taylorellae. Our results showed that infection of G.
      mellonella larvae with a high concentration of taylorellae did not induce overt
      G. mellonella mortality and that taylorellae were not able to proliferate within
      G. mellonella. In conclusion, G. mellonella larvae are resistant to taylorellae
      infection and therefore do not constitute a relevant alternative system for
      studying the virulence of taylorellae species. Significance and impact of the
      study: To date, the pathogenicity and host colonization capacity of Taylorella
      equigenitalis, the causative agent of contagious equine metritis (CEM) and T.
      asinigenitalis, the second species within the Taylorella genus, remain largely
      unknown. In this study, we evaluated the relevance of Galleria mellonella as an
      infection model for taylorellae; we showed that G. mellonella are resistant to
      taylorellae infection and therefore do not constitute a suitable host model for
      taylorellae.

PMID- 24945969
TI  - Antibody responses to Mycoplasma pneumoniae: role in pathogenesis and diagnosis
      of encephalitis?

PMID- 24945972
TI  - Daily physical activity, functional capacity and quality of life in patients with
      COPD.
AB  - INTRODUCTION: In the therapy of chronic obstructive pulmonary disease (COPD), it
      is a major goal to improve health-related quality of life (HRQOL). Patients with
      COPD often suffer from exertional dyspnea and adopt a sedentary lifestyle, which
      could be associated with poorer HRQOL. The aim of this study was to investigate
      the independent association of objectively measured daily physical activity and
      functional capacity with HRQOL in patients with COPD. METHODS: In this cross
      sectional study conducted at the University Hospital Basel, Switzerland, 87
      stable patients (58.6% male, mean age: 67.3 +/- 9.6 yrs) with COPD in GOLD grades
      I (n = 23), II (n = 46), III (n = 12) and IV (n = 6) were investigated. To assess
      HRQOL, the COPD assessment test (CAT) was completed. Patients performed
      spirometry and 6-min walk test. Physical activity was measured by the SenseWear
      Mini Armband on 7 consecutive days. By performing a multiple linear regression
      analysis, independent predictors of CAT score were identified. RESULTS: Age (beta
      = -0.39, p = 0.001), average daily steps (beta = -0.31, p = 0.033) and 6-min walk
      distance (beta = -0.32, p = 0.019) were found to be independent predictors of CAT
      score, whereas physical activity duration above 3 METs (p = 0.498) and forced
      expiratory volume in 1 s in% of predicted (p = 0.364) showed no significant
      association. CONCLUSIONS: This study showed that average daily steps and
      functional capacity are independent determinants of HRQOL in patients with COPD.
      This emphasizes the importance to remain active and mobile, which is associated
      with better HRQOL.

PMID- 24945973
TI  - Selective formation of gold(I) bis-phospholane macrocycles, polymeric chains, and
      nanotubes.
AB  - A series of highly flexible bis-phospholane ligands 3a-g with 5-11 methylene
      groups in the backbone was synthesized and fully characterized by mass
      spectrometry and NMR ((1)H, (13)C, (31)P) and IR spectroscopy. Gold bis
      phospholane macrocycles containing 16 ([Au2Cl2(MU-3a)2], 4), 20 ([Au2Cl2(MU
      3c)2], 5), 24 ([Au2Cl(MU-3e)2]Cl, 6), and 28 ([Au2Cl2(MU-3g)2], 7) atoms in the
      ring were obtained in one step from [AuCl(tht)] (tht = tetrahydrothiophene) and
      3a,c,e,g in excellent yield. In addition, three polymers resulting from
      aurophilic interactions, i.e., zigzag chains in [Au2Cl2(MU-3b)]x (8) and
      nanotubes in [Au2Cl2(MU-3d)]x (9) and [Au2Cl2(MU-3f)]x (10), with Au...Au
      distances of 309.41(2), 330.24(6), and 335.82(3) pm, respectively, were obtained.
      Halide abstraction of 4-7 with AgBF4 led to macrocycles [Au2(MU-3a)2](BF4)2 (11),
      [Au2(MU-3c)2](BF4)2 (12), [Au2(MU-3e)2](BF4)2 (13), and [Au2(MU-3g)2](BF4)2 (14).
      In 12, the monomers are connected by strong aurophilic interactions (Au...Au
      296.57(1) pm) in the solid state with formation of a polymeric chain. All
      complexes were fully characterized by NMR ((1)H, (13)C, (31)P) and IR
      spectroscopy, mass spectrometry, and X-ray diffraction. 

PMID- 24945974
TI  - Health care at the VA: recommendations for change.

PMID- 24945975
TI  - Effects of the magnetic resonance imaging contrast agent Gd-DTPA on plant growth
      and root imaging in rice.
AB  - Although paramagnetic contrast agents have a wide range of applications in
      medical studies involving magnetic resonance imaging (MRI), these agents are
      seldom used to enhance MRI images of plant root systems. To extend the
      application of MRI contrast agents to plant research and to develop related
      techniques to study root systems, we examined the applicability of the MRI
      contrast agent Gd-DTPA to the imaging of rice roots. Specifically, we examined
      the biological effects of various concentrations of Gd-DTPA on rice growth and
      MRI images. Analysis of electrical conductivity and plant height demonstrated
      that 5 mmol Gd-DTPA had little impact on rice in the short-term. The results of
      signal intensity and spin-lattice relaxation time (T1) analysis suggested that 5
      mmol Gd-DTPA was the appropriate concentration for enhancing MRI signals. In
      addition, examination of the long-term effects of Gd-DTPA on plant height showed
      that levels of this compound up to 5 mmol had little impact on rice growth and
      (to some extent) increased the biomass of rice. 

PMID- 24945976
TI  - Cancer incidence, survival and mortality: explaining the concepts.
AB  - Cancer incidence, survival and mortality are essential population-based
      indicators for public health and cancer control. Confusion and misunderstanding
      still surround the estimation and interpretation of these indicators. Recurring
      controversies over the use and misuse of population-based cancer statistics in
      health policy suggests the need for further clarification. In our article, we
      describe the concepts that underlie the measures of incidence, survival and
      mortality, and illustrate the synergy between these measures of the cancer
      burden. We demonstrate the relationships between trends in incidence, survival
      and mortality, using real data for cancers of the lung and breast from England
      and Sweden. Finally, we discuss the importance of using all three measures in
      combination when interpreting overall progress in cancer control, and we offer
      some recommendations for their use. 

PMID- 24945977
TI  - Combined experimental and theoretical study of the reactivity of gamma-Butyro-
      and related lactones, with the OH radical at room temperature.
AB  - The total rates of reaction between four cyclic esters (beta-butyro-, gamma
      butyro-, gamma-valero- and delta-valero-lactones) and the OH radical have been
      measured relative to the rate of reaction of a reference compound, ethene, at
      room temperatures. The measurements show that the rates increase with increasing
      ring size. Theoretical calculations on the four lactones with the inclusion of a
      fifth, alpha-methyl-gamma-butyrolactone, are broadly in agreement with this
      picture but provide a more insightful view of the sites at which hydrogen atom
      abstraction occurs in each molecule. 

PMID- 24945978
TI  - Advanced oxidation of iodinated X-ray contrast media in reverse osmosis brines:
      the influence of quenching.
AB  - Among the main restrictions for the implementation of advanced oxidation
      processes (AOPs) for removal of micropollutants present in reverse osmosis (RO)
      brines of secondary effluents account the quenching performed by background
      organic and inorganic constituents. Natural organic matter (NOM) and soluble
      microbial products (SMP) are the main effluent organic matter constituents. The
      inorganic fraction is largely constituted by chlorides and bicarbonate alkalinity
      with sodium and calcium as main counterions. The quenching influence of these
      components, separately and their mixture, in the transformation of model
      compounds by UVA/TiO2 was studied applying synthetic brines solutions mimicking 2
      fold concentrated RO secondary effluents brines. The results were validated using
      fresh RO brines. Diatrizoate (DTZ) and iopromide (IOPr) were used as model
      compound. They have been found to exhibit relative high resistance to oxidation
      process and therefore represent good markers for AOPs techniques. Under the
      conditions applied, oxidization of DTZ in the background of RO brines was
      strongly affected by quenching effects. The major contribution to quenching
      resulted from organic matter (~70%) followed by bicarbonate alkalinity (~30%).
      NOM displayed higher quenching than SMP in spite of its relative lower
      concentration. Multivalent cations, i.e., Ca(+2), were found to decrease
      effectiveness of the technique due to agglomeration of the catalyst. However this
      influence was lowered in presence of NOM. Different patterns of transformation
      were found for each model compound in which a delayed deiodination was observed
      for iopromide whereas diatrizoate oxidation paralleled deiodination. 

PMID- 24945980
TI  - Self-assembled organic monolayers on epitaxial graphene with enhanced structural
      and thermal stability.
AB  - Scanning tunnelling microscopy and X-ray reflectivity are used to characterize
      adlayers of perylenetetracarboxylic diimide (PTCDI) deposited on epitaxial
      graphene (EG) on SiC(0001). PTCDI adopts a herringbone structural phase on EG/SiC
      that can accommodate sub-5 nm voids with molecularly defined boundaries and
      isolated molecular vacancies at room temperature. The PTCDI monolayer remains
      intact up to substrate temperatures of ~260  degrees C, thus demonstrating
      enhanced thermal stability compared to previously studied perylene derivatives on
      EG/SiC.

PMID- 24945979
TI  - Effects of pH on the speciation coefficients in models of bromide influence on
      the formation of trihalomethanes and haloacetic acids.
AB  - This study investigated effects of pH, bromide and natural organic matter (NOM)
      level on yields and speciation of trihalomethanes (THMs) and haloacetic acids
      (HAAs) in chlorinated water. Experimental data were obtained using two water
      sources, one with a medium (DOC = 1.4 mg/L and SUVA = 2.60 L mg(-1) m(-1)) and
      the other with higher (DOC = 7.7 mg/L and SUVA = 4.26 L mg(-1) m(-1)) organic
      carbon level. The experiments employed the simulated distribution system (SDS)
      procedure at varying bromide concentrations and pH values of 7.0, 8.5 and 10. The
      speciation of THMs and dihalogenated HAAs (DHAAs) was interpreted based on the
      modelling of mixed halogenation yields via dimensionless ratios of
      bromination/chlorination reaction rates at each halogen incorporation node. The
      approach allowed precise modelling of the speciation of THMs and DHAAs at all
      examined pHs. In the case of DHAA, the dimensionless ratios of the
      bromination/chlorination reaction rates were not consistently affected by pH
      variations. For THMs, increase of pH caused the values of the dimensionless
      bromination/chlorination reaction rates to decrease in the case of halogenation
      of the initial reaction sites indicating a decreasing preference toward
      bromination at this reaction node. A similar trend was observed for the
      reactivity of dichlorinated reaction intermediate denoted as SCl2 whose formation
      precedes the release of CHCl3 and CHBrCl2. A similar but less consistent trend
      was observed for intermediate SBrCl whose halogenation yields both CHBrCl2 and
      CHBr2Cl. An opposite trend of increasing preference towards bromination at higher
      pHs was observed monobrominated intermediate SBr and in some extent dibrominated
      intermediate SBr2. These results help develop detailed DBP speciation models
      which needed to better understand the generation and potential health effects of
      THMs and HAAs at varying operating conditions and ultimately to adopt measure to
      minimize their levels in drinking water systems.

PMID- 24945982
TI  - Endoscopic gastric pouch plication - a novel endoluminal incision free approach
      to revisional bariatric surgery.
AB  - 10-40% of Roux-en-Y gastric bypass (RYGB) patients regain significant weight
      after Roux-en-Y gastric bypass surgery due to dilation of the pouch and/or the
      gastrojejunal (GJ) anastomosis. Traditional revision surgery is associated with
      significant morbidity (e.g. post-anastomotic GJ leak) where less invasive
      endoluminal procedures may represent safer alternatives. The present article
      reports a case of the safe and successful use of endoluminal gastric pouch
      plication (EGPP) using the StomaphyXTM device to correct both a dilated gastric
      pouch and a dilated gastrojejunostomy in a post-RYGB patient who regained
      significant weight. 

PMID- 24945981
TI  - Two cases of Scimitar syndrome associated with multiple congenital skeletal
      anomalies and lacking abnormalities by genomic microarray analysis.
AB  - Scimitar syndrome is a congenital anomaly occurring in approximately 1/50,000
      births, consisting of partial anomalous pulmonary venous return, right lung
      hypoplasia, and several associated defects. The condition generally has
      significant morbidity and mortality, but the underlying cause is poorly
      understood. In this report, we describe 2 autopsy cases of Scimitar syndrome
      associated with multiple skeletal anomalies and attempt to characterize possible
      genetic abnormalities in this condition. In light of these findings, we discuss
      the embryology and direct timing during development of the anomalies associated
      with this syndrome.

PMID- 24945983
TI  - Delayed presentation of small bowel injury during suprapubic catheterisation.
AB  - We present a case of small intestine injury resulting from suprapubic catheter
      insertion. This case is of particular interest for three reasons. Firstly, the
      presentation of the injury was delayed by three months, until the time of the
      first catheter exchange. Secondly, the injury was managed conservatively, without
      surgical exploration. Finally, the injury occurred using a newer, Seldinger-type
      suprapubic catheter insertion kit. 

PMID- 24945984
TI  - New onset epilepsy following unintentional durotomy in a patient on anti
      psychiatric medication.
AB  - We would like to present a rare case report describing a case in which new-onset
      tonic-clonic seizures occurred following an unintentional durotomy during lumbar
      discectomy and decompression. Unintentional durotomy is a frequent complication
      of spinal surgical procedures, with a rate as high as 17%. To our knowledge a
      case of new onset epilepsy has never been reported in the literature. Although
      dural tears during surgery and CSF hypovolaemia are thought to be the main
      contributing factors, one postulates on the effects of anti-psychiatric
      medication with epileptogenic properties. Amisulpride and Olanzapine can lower
      seizure threshold and should be used with caution in patients previously
      diagnosed with epilepsy. However manufacturers do not state that in cases where
      the seizure threshold is already lowered by CSF hypotension, new onset epilepsy
      might be commoner. Finally, strong caution and aggressive post-operative
      monitoring is advised for patients with CSF hypotension in combination with
      possible epileptogenic medication. 

PMID- 24945985
TI  - Unruptured Pseudoaneurysm of the cystic artery associated with acute calculus
      cholecystitis.
AB  - Cystic artery pseudoaneurysm (CAP) is a very rare complication of acute
      cholecystitis. We present the unruptured cystic artery pseudoaneurysm of an
      oedematous, thick-walled gallbladder in a 71-year old gentleman admitted with
      acute calculus cholecystitis. This was managed by radiological microcoil
      embolisation, percutaneous drainage of pericholic fluid and conservative
      treatment with antibiotics. 

PMID- 24945986
TI  - Stercoral perforation of the colon in pregnancy.
AB  - We report a 37 year old multi-parous lady, who in her third trimester of
      pregnancy, presented to the emergency room with acute diffuse abdominal pain and
      involuntary guarding. Findings on physical examination were consistent with
      peritonitis and a decision was made by the admitting team to perform an urgent
      laparotomy which surprisingly showed a stercoral perforation of the colon. 

PMID- 24945988
TI  - Factors influencing the use of RT in NSW: a qualitative study exploring consumer
      and health professional perspectives.
AB  - INTRODUCTION: Radiotherapy (RT) is an essential and cost-effective cancer
      treatment. It is underutilised in Australia. Bridging the gap between actual and
      optimal RT utilisation requires not only provision of adequate RT infrastructure
      but also an understanding of the factors that influence the extent to which this
      opportunity for RT is utilised. This study explored factors perceived to affect
      RT-related decision making by consumers and health professionals (HPs). METHODS:
      Six semi-structured focus groups (FGs) and 13 interviews were conducted at three
      geographical locations in NSW, Australia (n = 26 consumers and 30 HPs). Audio
      recordings of FGs and interviews were transcribed verbatim and analysed
      thematically. RESULTS: An exhaustive list of issues perceived to affect consumer
      and HP RT decisions was identified. There were common themes across participant
      groups and locations. Perceptions of RT and its benefits, as well as accurate
      communication of the expected benefits and risks of RT, were highlighted as
      important to decision making. Perceived factors relating to 'inconvenience' of RT
      were multifaceted and included travel, relocation, accommodation, time away from
      work and financial challenges. Perceived potential barriers to RT referral
      included knowledge of RT and RT services, availability of a local or visiting RT
      service, referrer bias, and the low profile of RT. CONCLUSIONS: Important drivers
      during RT decisions appear to include the perceived benefit, risks and
      inconvenience of RT. Underutilisation of RT may also result from multiple
      barriers at the referrer level. Further research into whether these factors
      influence actual RT decisions is needed.

PMID- 24945987
TI  - An expanded Notch-Delta model exhibiting long-range patterning and incorporating
      MicroRNA regulation.
AB  - Notch-Delta signaling is a fundamental cell-cell communication mechanism that
      governs the differentiation of many cell types. Most existing mathematical models
      of Notch-Delta signaling are based on a feedback loop between Notch and Delta
      leading to lateral inhibition of neighboring cells. These models result in a
      checkerboard spatial pattern whereby adjacent cells express opposing levels of
      Notch and Delta, leading to alternate cell fates. However, a growing body of
      biological evidence suggests that Notch-Delta signaling produces other patterns
      that are not checkerboard, and therefore a new model is needed. Here, we present
      an expanded Notch-Delta model that builds upon previous models, adding a local
      Notch activity gradient, which affects long-range patterning, and the activity of
      a regulatory microRNA. This model is motivated by our experiments in the ascidian
      Ciona intestinalis showing that the peripheral sensory neurons, whose
      specification is in part regulated by the coordinate activity of Notch-Delta
      signaling and the microRNA miR-124, exhibit a sparse spatial pattern whereby
      consecutive neurons may be spaced over a dozen cells apart. We perform rigorous
      stability and bifurcation analyses, and demonstrate that our model is able to
      accurately explain and reproduce the neuronal pattern in Ciona. Using Monte Carlo
      simulations of our model along with miR-124 transgene over-expression assays, we
      demonstrate that the activity of miR-124 can be incorporated into the Notch decay
      rate parameter of our model. Finally, we motivate the general applicability of
      our model to Notch-Delta signaling in other animals by providing evidence that
      microRNAs regulate Notch-Delta signaling in analogous cell types in other
      organisms, and by discussing evidence in other organisms of sparse spatial
      patterns in tissues where Notch-Delta signaling is active. 

PMID- 24945989
TI  - Cod liver oil in sodium nitrite induced hepatic injury: does it have a potential
      protective effect?
AB  - OBJECTIVES: Exposure to sodium nitrites, a food additive, at high levels has been
      reported to produce reactive nitrogen and oxygen species that cause dysregulation
      of inflammatory responses and tissue injury. In this work, we examined the impact
      of dietary cod liver oil on sodium nitrite-induced inflammation in rats. METHODS:
      Thirty-two adult male Sprague-Dawely rats were treated with 80 mg/kg sodium
      nitrite in presence/absence of 5 ml/kg cod liver oil. Liver sections were stained
      with hematoxylin/eosin. We measured hepatic tumor necrosis factor (TNF)-alpha,
      interleukin-1 beta (IL)-1beta, C-reactive protein (CRP), transforming growth
      factor (TGF)-beta1, and caspase-3. RESULTS: Cod liver oil reduced sodium nitrite
      induced hepatocyte damage. In addition, cod liver oil results in reduction of
      hepatic TNF-alpha, IL-1beta, CRP, TGF-beta1, and caspase-3 when compared with the
      sodium nitrite group. DISCUSSION: Cod liver oil ameliorates sodium nitrite
      induced hepatic injury via multiple mechanisms including blocking sodium nitrite
      induced elevation of inflammatory cytokines, fibrosis mediators, and apoptosis
      markers.

PMID- 24945991
TI  - Low Skeletal Bone Mineral Density Does Not Affect Dental Implants.
AB  - The aim of this case-control study (n = 30) was to evaluate the effects of
      osteoporosis/osteopenia on the success of dental implants. Twenty healthy females
      ages 50-80 with confirmed osteoporosis or osteopenia, and 10 age- and gender
      matched subjects with normal bone density (controls) received dental implants.
      Dual-energy X-ray absorptiometry (DXA) scans at 5 standard sites (total body,
      hip, spine [lateral and anterior-posterior] and radius) were measured at baseline
      and 24 months. Periapical and panoramic radiographs were taken at baseline before
      implant placement; 1 periapical radiograph was taken immediately after placement
      of the dental implant. Since implants are standard sizes, periapical bone loss
      was measured from the first implant thread to the level of alveolar bone at
      baseline, 12 months, and 24 months via 1 periapical radiograph. All subjects
      received implants of the same manufacturer (NobelBiocare). One subject was a
      smoker. Three subjects with osteoporosis had received prior treatment with
      Fosamax, 1 received Fortical, and 1 Forteo. In all 3, there was slight
      improvement in DXA after 24 months. All implants remained successful with no
      evidence of bone loss after 24 months. These investigators conclude that implants
      placed in individuals with confirmed skeletal osteoporosis can be successful,
      with no clinical differences to implants placed in healthy individuals. Although
      3 subjects with osteoporosis had treatment with oral bisphosphonates, no side
      effects were noted and no bone necrosis of the jaw was observed. Further
      investigation with larger sample sizes and longer periods of time for treatment
      with oral bisphosphonates is recommended to confirm these results. 

PMID- 24945990
TI  - Survivin delta Ex3 overexpression in thyroid malignancies.
AB  - CONTEXT: Thyroid cancer incidence has increased significantly during the past
      decades and is the most common type of endocrine malignancy. Many factors in
      thyroid cancers were studied as independent predictors of a poor prognosis.
      OBJECTIVE: The objective of the study was to evaluate survivin expression - BIRC5
      and its splice variants: survivin delta Ex3 and survivin 2B in benign and
      malignant thyroid nodules. DESIGN: Thyroid tissues samples from a group of 50
      patients consisting of: 29 patients with thyroid cancers (including medullary,
      papillary, follicular and undifferentiated types), as well as from 21 patients
      with non-cancerous thyroid tissues (including: 11 benign thyroid lesions and 10
      healthy thyroid samples). MAIN OUTCOME MEASURES: The analysis of the survivin
      gene expression and evaluation of the level of splice variants were performed
      using quantitative RT-PCR. RESULTS: A statistically significant higher level of
      expression of survivin gene - BIRC5 was detected in thyroid malignant nodules,
      when compared with benign lesions and healthy thyroid samples. Moreover, the
      comparison of survivin relative expression in different staged tumors (pT1, pT3,
      and pT4) revealed a much higher amount of BIRC5 transcripts in tumor tissues of
      pT3/pT4. The comparison of survivin expression between benign thyroid nodules and
      healthy thyroid did not reveal significant differences. Importantly, high
      expression rate of the survivin delta Ex3 splice variant characterized thyroid
      carcinomas. CONCLUSION: The results suggest that survivin, especially survivin
      delta Ex3 splice variant being overexpress, is a characteristic feature of
      thyroid malignancy.

PMID- 24945992
TI  - The life cycle of Pseudosellacotyla lutzi (Digenea: Cryptogonimidae), in
      Aylacostoma chloroticum (Prosobranchia: Thiaridae), and Hoplias malabaricus
      (Characiformes: Erythrinidae), in Argentina.
AB  - Pseudosellacotyla lutzi ( Freitas, 1941), at present included in the Faustulidae,
      is redescribed, and its life cycle was resolved experimentally. The prosobranch
      snail Aylacostoma chloroticum Hylton Scott (Thiaridae), collected in the Yacyreta
      Dam, Province of Misiones, Argentina, was found naturally infected with cercariae
      that lacked pigmented eyespots, and possessed 7 pairs of penetration glands, 8
      pairs of flame cells, and a V-shaped excretory vesicle. The cercariae developed
      in oval cysts, which were found on fin rays, vertebrae, and spines of poeciliid
      and tetragonopterid fish species. Adults were obtained experimentally from
      Hoplias malabaricus (Erythrinidae) infected with metacercariae from albino
      Gymnocorymbus ternetzi (Tetragonopteridae), which had been exposed to emerging
      cercariae. Adults were also found in naturally infected H. malabaricus collected
      in the Yacyreta Dam. The morphology of the cercariae, and the characteristics of
      the life cycle show that P. lutzi should be included in the Cryptogonimidae.

PMID- 24945993
TI  - Photosensitivity in mild traumatic brain injury (mTBI): a retrospective analysis.
AB  - PRIMARY OBJECTIVE: To determine whether photosensitivity (PS) changes over time
      and, if so, what factors may be related to the change; furthermore, to determine
      whether tint density changes over time, all in mild traumatic brain injury
      (mTBI). DESIGN AND METHODS: A retrospective analysis of 62 patient records (aged
      18-40 years) with mTBI and PS was conducted. All charts were obtained from the
      SUNY/College of Optometry clinics from 2004-2011. RESULTS: Fifty per cent
      demonstrated reduced PS over time, with most occurring after year 1 post-injury
      (40%). Promotion of PS reduction appears to be associated with the lack of
      spectacle tint usage (p = 0.01) and the use of contact lenses (p = 0.03).
      Inhibition of PS reduction appears to be associated with tinted lenses (p =
      0.06), hyperacusis (p = 0.03), dry eye (p = 0.04), migraines (p = 0.03) and loss
      of consciousness at the time of injury (p = 0.05). Concerning tint density
      changes over time, 71% (p = 0.002) maintained the same degree over time, while
      27% (p = 0.002) reduced and 2% waxed and waned. CONCLUSION: Neural adaptation to
      PS appears to be a long-term process. Tint usage may act to inhibit this adaptive
      process, while the use of contact lenses may act to promote it. These findings
      may provide guidance in the clinical management of photosensitivity in the mTBI
      population.

PMID- 24945994
TI  - Nanoparticles as drug delivery system against tuberculosis in zebrafish embryos:
      direct visualization and treatment.
AB  - Nanoparticles (NPs) enclosing antibiotics have provided promising therapy against
      Mycobacterium tuberculosis (Mtb) in different mammalian models. However, the NPs
      were not visualized in any of these animal studies. Here, we introduce the
      transparent zebrafish embryo as a system for noninvasive, simultaneous imaging of
      fluorescent NPs and the fish tuberculosis (TB) agent Mycobacterium marinum (Mm).
      The study was facilitated by the use of transgenic lines of macrophages,
      neutrophils, and endothelial cells expressing fluorescent markers readily visible
      in the live vertebrate. Intravenous injection of Mm led to phagocytosis by blood
      macrophages. These remained within the vasculature until 3 days postinfection
      where they started to extravasate and form aggregates of infected cells.
      Correlative light/electron microscopy revealed that these granuloma-like
      structures had significant access to the vasculature. Injection of NPs induced
      rapid uptake by both infected and uninfected macrophages, the latter being
      actively recruited to the site of infection, thereby providing an efficient
      targeting into granulomas. Rifampicin-loaded NPs significantly improved embryo
      survival and lowered bacterial load, as shown by quantitative fluorescence
      analysis. Our results argue that zebrafish embryos offer a powerful system for
      monitoring NPs in vivo and rationalize why NP therapy was so effective against
      Mtb in earlier studies; bacteria and NPs share the same cellular niche. 

PMID- 24945995
TI  - Chemosignals, hormones, and amphibian reproduction.
AB  - This article is part of a Special Issue "Chemosignals and Reproduction".
      Amphibians are often thought of as relatively simple animals especially when
      compared to mammals. Yet the chemosignaling systems used by amphibians are varied
      and complex. Amphibian chemosignals are particularly important in reproduction,
      in both aquatic and terrestrial environments. Chemosignaling is most evident in
      salamanders and newts, but increasing evidence indicates that chemical
      communication facilitates reproduction in frogs and toads as well. Reproductive
      hormones shape the production, dissemination, detection, and responsiveness to
      chemosignals. A large variety of chemosignals have been identified, ranging from
      simple, invariant chemosignals to complex, variable blends of chemosignals.
      Although some chemosignals elicit straightforward responses, others have
      relatively subtle effects. Review of amphibian chemosignaling reveals a number of
      issues to be resolved, including: 1) the significance of the complex,
      individually variable blends of courtship chemosignals found in some salamanders,
      2) the behavioral and/or physiological functions of chemosignals found in anuran
      "breeding glands", 3) the ligands for amphibian V2Rs, especially V2Rs expressed
      in the main olfactory epithelium, and 4) the mechanism whereby transdermal
      delivery of chemosignals influences behavior. To date, only a handful of the more
      than 7000 species of amphibians has been examined. Further study of amphibians
      should provide additional insight to the role of chemosignals in reproduction. 

PMID- 24945996
TI  - Pu-erh tea has in vitro anticancer activity in TCA8113 cells and preventive
      effects on buccal mucosa cancer in U14 cells injected mice in vivo.
AB  - Pu-erh tea is a functional tea production in China. The functional effects should
      be proved. The oral cancer preventive and antimetastatic effects of Pu-erh tea in
      vitro and in vivo have been studied respectively. Pu-erh tea showed an inhibitory
      effect on human tongue carcinoma TCA8113 cells proliferation tested by 3-(4,5
      Dimethyl-2-Thiazolyl)-2,5-Diphenyltetrazolium Bromide assay and induced TCA8113
      apoptosis shown anticancer effect. The antimetastatic effect of Pu-erh tea in
      TCA8113 cells was proved by the decreasing of matrix metalloproteinases (MMPs)
      and increasing of tissue inhibitors of metalloproteinases (TIMPs) mRNA
      transcription. In the animal experiments, the tumor volumes and lymph node
      metastasis rates of Pu-erh tea-treated mice were smaller than control mice. Pu
      erh tea reduced the levels of the serum proinflammatory cytokines interleukin
      (IL)-6, IL-12, tumor necrosis factor-alpha, and interferon-gamma to a greater
      extent compared with the control mice, and the levels of 200 MUg/mL treatment was
      more close to the normal mice than 100 MUg/mL treated mice. Pu-erh tea also
      significantly induced apoptosis in tissues of mice (P < 0.05) by upregulating Bax
      and downregulating Bcl-2. These results demonstrate Pu-erh tea has cancer
      preventive and anti-metastatic effects on buccal mucosa cancer, the higher
      concentration get better efficiency. 

PMID- 24945997
TI  - Aspirin use and survival after the diagnosis of breast cancer: a population-based
      cohort study.
AB  - BACKGROUND: Aspirin use has been associated with a reduced cancer incidence and
      fewer deaths from cancer. This study examined whether women with breast cancer
      prescribed aspirin postdiagnosis had improved survival. METHODS: An
      observational, population cohort study was undertaken using data linkage of
      cancer registry, dispensed prescriptions and death records in Tayside, Scotland.
      All community prescriptions for aspirin in women with breast cancer were
      extracted and use postdiagnosis for each individual examined using Cox's
      proportional hazard models. The main outcome measures were all-cause mortality
      and breast cancer-specific mortality. RESULTS: Four thousand six hundred and
      twenty-seven patients diagnosed with breast cancer between 1 January 1998 and 31
      December 2008 were followed up until 28 February 2010. Median age at diagnosis
      was 62 (IQR 52-74). One thousand eight hundred and two (39%) deaths were
      recorded, with 815 (18%) attributed to breast cancer. One thousand and thirty
      five (22%) patients were prescribed aspirin postdiagnosis. Such aspirin use was
      associated with lower risk of all-cause mortality (HR=0.53, 95% CI=0.45-0.63,
      P<0.001) and breast cancer-specific mortality (HR=0.42, 95% CI=0.31-0.55,
      P<0.001) after adjusting for age, socioeconomic status, TNM stage, tumour grade,
      oestrogen receptor status, surgery, radiotherapy, chemotherapy, adjuvant
      endocrine therapy and aspirin use prediagnosis. CONCLUSIONS: Aspirin use
      postdiagnosis of breast cancer may reduce both all-cause and breast cancer
      specific mortality. Further investigation seeking a causal relationship and which
      subgroups of patients benefit most await ongoing randomised controlled trials.

PMID- 24945998
TI  - Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, potentiate
      the anti-angiogenic effects of bevacizumab by suppressing angiopoietin2, BiP, and
      Hsp90alpha in human colorectal cancer.
AB  - BACKGROUND: Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,
      are commonly prescribed because of their therapeutic and preventive effects on
      cardiovascular diseases. Even though they have been occasionally reported to have
      antitumour activity, it is unknown whether statins have anti-angiogenic effect in
      human colorectal cancer (CRC). METHODS: A total of 11 human CRC cell lines were
      used to test the effects of bevacizumab, statins, and bevacizumab plus statins on
      human umbilical vein endothelial cell (HUVEC) viability and invasion in vitro. To
      determine the molecular mechanism of statins as anti-angiogenic agents, we
      performed an angiogenesis antibody array and proteomics analysis and confirmed
      the results using immunoblot assay, HUVEC invasion rescue assay, and siRNA assay.
      The antitumoural effects of bevacizumab and statins were evaluated in xenograft
      models. RESULTS: A conventional dose of statins (simvastatin 0.2 MUM, lovastatin
      0.4 MUM, atorvastatin 0.1 MUM, and pravastatin 0.4 MUM) in combination with
      bevacizumab directly reduced the cell viability, migration, invasion, and tube
      formation of HUVECs. The culture media of the CRC cells treated with bevacizumab
      or statins were also found to inhibit HUVEC invasion by suppressing angiogenic
      mediators, such as angiopoietin2, binding immunoglobulin protein (BiP), and
      Hsp90alpha. The combined treatment with bevacizumab and simvastatin significantly
      reduced the growth and metastases of xenograft tumours compared with treatment
      with bevacizumab alone. CONCLUSIONS: The addition of simvastatin at a dose used
      in patients with cardiovascular diseases (40-80 mg once daily) may potentiate the
      anti-angiogenic effects of bevacizumab on CRC by suppressing angiopoietin2, BiP,
      and Hsp90alpha in cancer cells. A clinical trial of simvastatin in combination
      with bevacizumab in patients with CRC is needed.

PMID- 24945999
TI  - The pro-apoptotic role of autophagy in breast cancer.
AB  - BACKGROUND: Autophagy is a catabolic process that has a vital role in cancer
      progression and treatment. Current chemotherapeutic agents, which target
      autophagy, result in growth inhibition in many cancer types. In this study, we
      examined the role of autophagy in breast cancer (BCa) patients as well as BCa
      cell lines. METHODS: Tissue microarray was used to detect the expression of an
      autophagy marker, LC3B in BCa patients (normal/hyperplasia=8; grade-I=15, grade
      II=84, and grade-III=27) and BCa cell lines. To modulate the activation of
      autophagy, we used novel herbal compound nimocinol acetate (NA) in BCa cell lines
      and the anticancer activity was measured by phenotypic and molecular analysis.
      RESULTS: LC3B is highly expressed in tumours as compared with normal tissues.
      Activation of LC3B in NA-treated BCa (MCF-7 and MDA-MB-231) cells was evident as
      compared with other autophagy makers. Further, our results confirmed that NA
      transcriptionally regulates LC3B (as confirmed by mRNA levels and reporter
      assay), which resulted in the formation of acidic autophagy vesicles and
      autolysosomes in BCa cells. Nimocinol acetate inhibited mTOR-mediated pro
      survival signalling that resulted in inhibition of growth in BCa cells without
      affecting normal breast epithelial cells. Downregulation of LC3B expression by
      siRNA significantly inhibited the anticancer effects of NA in BCa cells.
      CONCLUSIONS: Together, our results suggest that LC3B is highly expressed in BCa
      tissues and increasing the threshold of LC3B activation dictates the pro
      apoptotic function, which in turn, suppresses the growth of BCa cells. Nimocinol
      acetate could be a potential agent for treatment of BCa.

PMID- 24946000
TI  - First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with
      mCRC: GEMCAD phase II BECOX study.
AB  - BACKGROUND: Subgroup analyses of clinical studies suggest that bevacizumab plus
      XELOX is effective and tolerable in elderly patients with metastatic colorectal
      cancer (mCRC). The prospective BECOX study examined the efficacy and safety of
      bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly
      patients with mCRC. METHODS: Patients aged ?70 years with Eastern Cooperative
      Oncology Group performance status 0 out of 1 and confirmed mCRC were included.
      Patients received bevacizumab 7.5 mg kg(-1) and oxaliplatin 130 mg m(-2) on day
      1, plus capecitabine 1000 mg m(-2) bid orally on days 1-14 every 21 days;
      oxaliplatin was discontinued after 6 cycles. The primary end point was time to
      progression (TTP). RESULTS: The intent-to-treat population comprised 68 patients
      (65% male, median age 76 years). Median TTP was 11.1 months; median overall
      survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse
      events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events
      of special interest for bevacizumab included deep-vein thrombosis (6%) and
      pulmonary embolism (4%). CONCLUSIONS: Bevacizumab plus XELOX was effective and
      well tolerated in elderly patients in the BECOX study. The adverse-event profile
      was similar to previous reports; no new safety concerns were identified. Fit
      elderly patients with mCRC should be considered for treatment with bevacizumab
      plus XELOX.

PMID- 24946004
TI  - A single incision for harvesting conchal cartilage and temporal fascia in diced
      cartilage-fascia grafts.

PMID- 24946005
TI  - Interfacial dynamics and adhesion behaviors of water and oil droplets in confined
      geometry.
AB  - To simulate the interfacial behaviors in real heterogeneous systems, the point
      contact condition is constructed to study the classical immiscible displacement
      problem in this work. Specifically, the interfacial dynamics during the water
      droplet passing through the oil capillary bridge formed under the point contact
      condition is investigated. Emphasis is put on the influences of the wettabilities
      and the relative separation motion of the solid surfaces on the dynamic behavior
      of the droplets. The observations suggested that the capillary pressure had
      negligible effect on the movement of the water droplet when it was passing though
      the oil capillary bridge. The wettability and the relative separation of the disk
      and ball would influence the final adhesion behaviors of the water droplet after
      the droplet passed through the oil capillary bridge. Surface tension and adhesion
      energy were used to interpret these observations. 

PMID- 24946003
TI  - Formulation of cidofovir improves the anti-papillomaviral activity of topical
      treatments in the CRPV/rabbit model.
AB  - Current topical treatments for papillomas use ablative, cytotoxic and
      immunomodulating strategies and reagents. However, the effectiveness of topical
      treatments using different formulations has not been examined in preclinical
      models or clinical trials. The purpose of this study was to determine whether
      formulation of the small molecule acyclic nucleoside, cidofovir (CDV), could lead
      to improved therapeutic endpoints following topical treatment of papillomas using
      the cottontail rabbit papillomavirus (CRPV)/rabbit model. Different formulations
      with a set dose of 1% cidofovir were tested to establish comparative data. The
      results demonstrated that anti-papilloma treatments with topical CDV were greatly
      enhanced when formulated versus unformulated. Best results were obtained with CDV
      formulated in cremophor, then in Carbomer 940, and then in DMSO. Further studies
      indicated that effective formulations led to complete cures of papillomas at
      dilutions less than 0.3% CDV. These studies together with previous observations
      demonstrated that unformulated CDV under the same treatment regime required doses
      of 2% to achieve cures demonstrating that much less compound can be used when
      properly formulated. 

PMID- 24946001
TI  - Feasibility study of a randomised controlled trial to compare (deferred) androgen
      deprivation therapy and cryotherapy in men with localised radiation-recurrent
      prostate cancer.
AB  - BACKGROUND: Salvage therapeutic options for biochemical failure after primary
      radiation-based therapy include radical prostatectomy, cryoablation, high
      intensity focused ultrasound (HIFU), brachytherapy (for post-EBRT patients) and
      androgen deprivation therapy (ADT). ADT and salvage prostate cryoablation (SPC)
      are two commonly considered treatment options for RRPC. However, there is an
      urgent need for high-quality clinical studies to support evidence-based decisions
      on treatment choice. Our study aims to determine the feasibility of randomising
      men with RRPC for treatment with ADT and SPC. METHODS: The randomised controlled
      trial (CROP) was developed, which incorporated protocols to assess parameters
      relating to cryotherapy procedures and provide training workshops for optimising
      patient recruitment. Analysis of data from the recruitment phase and patient
      questionnaires was performed. RESULTS: Over a period of 18 months, 39 patients
      were screened for eligibility. Overall 28 patients were offered entry into the
      trial, but only 7 agreed to randomisation. The majority reason for declining
      entry into the trial was an unwillingness to be randomised into the study.
      'Having the chance of getting cryotherapy' was the major reason for accepting the
      trial. Despite difficulty in retrieving cryotherapy temperature parameters from
      prior cases, 9 of 11 cryotherapy centres progressed through the Cryotherapists
      Qualification Process (CQP) and were approved for recruiting into the CROP study.
      CONCLUSIONS: Conveying equipoise between the two study arms for a salvage therapy
      was challenging. The use of delayed androgen therapy may have been seen as an
      inferior option. Future cohort studies into available salvage options (including
      prostate cryotherapy) for RRPC may be more acceptable to patients than
      randomisation within an RCT.

PMID- 24946006
TI  - Amphiphilic cellulose nanocrystals from acid-free oxidative treatment:
      physicochemical characteristics and use as an oil-water stabilizer.
AB  - A chemical pretreatment for producing cellulose nanocrystals (CNCs) with
      periodate oxidation and reductive amination is reported. This new
      functionalization of cellulose fibers dispenses an alternative method for
      fabricating individual CNCs without the widely used acid hydrolysis process. CNCs
      can be directly modified during the pretreatment step, and no additional post
      treatments are required to tune the surface properties. Three butylamine isomers
      were tested to fabricate CNCs with amphiphilic features. After mechanical
      homogenization, CNCs occurred as individual crystallinities without aggregation
      where high uniformity in terms of shape and size was obtained. The elemental
      analysis and (1)H NMR measurement show that iso- and n-butylamine attach the
      highest number of butylamino groups to the cellulose fibers. Linking the alkyl
      groups increases the hydrophobic nature of the CNCs, where water contact angles
      from self-standing films up to 110.5 degrees  are reported. Since these
      butylamino-functionalized CNCs have hydrophobic characteristics in addition to
      the hydrophilic backbone of cellulose, the stabilization impact on oil/water
      emulsions is demonstrated as a potential application. 

PMID- 24946002
TI  - KPT-330 has antitumour activity against non-small cell lung cancer.
AB  - BACKGROUND: We investigated the biologic and pharmacologic activities of a
      chromosome region maintenance 1 (CRM1) inhibitor against human non-small cell
      lung cancer (NSCLC) cells both in vitro and in vivo. METHODS: The in vitro and in
      vivo effects of a novel CRM1 inhibitor (KPT-330) for a large number of anticancer
      parameters were evaluated using a large panel of 11 NSCLC cell lines containing
      different key driver mutations. Mice bearing human NSCLC xenografts were treated
      with KPT-330, and tumour growth was assessed. RESULTS: KPT-330 inhibited
      proliferation and induced cell cycle arrest and apoptosis-related proteins in 11
      NSCLC cells lines. Moreover, the combination of KPT-330 with cisplatin
      synergistically enhanced the cell kill of the NSCLC cells in vitro. Human NSCLC
      tumours growing in immunodeficient mice were markedly inhibited by KPT-330. Also,
      KPT-330 was effective even against NSCLC cells with a transforming mutation of
      either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA,
      suggesting the drug might be effective against a variety of lung cancers
      irrespective of their driver mutation. CONCLUSIONS: Our results support clinical
      testing of KPT-330 as a novel therapeutic strategy for NSCLC.

PMID- 24946007
TI  - Valence-to-core-detected X-ray absorption spectroscopy: targeting ligand
      selectivity.
AB  - X-ray absorption spectroscopy (XAS) can provide detailed insight into the
      electronic and geometric structures of transition-metal active sites in
      metalloproteins and chemical catalysts. However, standard XAS spectra inherently
      represent an average contribution from the entire coordination environment with
      limited ligand selectivity. To address this limitation, we have investigated the
      enhancement of XAS features using valence-to-core (VtC)-detected XAS, whereby XAS
      spectra are measured by monitoring fluorescence from valence-to-core X-ray
      emission (VtC XES) events. VtC emission corresponds to transitions from filled
      ligand orbitals to the metal 1s core hole, with distinct energetic shifts for
      ligands of differing ionization potentials. VtC-detected XAS data were obtained
      from multiple valence emission features for a series of well-characterized Mn
      model compounds; taken together, these data correspond to a VtC resonant XES (VtC
      RXES) plane. For comparison, standard total fluorescence yield (TFY) XAS and
      nonresonant XES data were obtained. Dramatic intensity variations and the
      appearance of new features were observed in the pre-edge region by detecting at
      different VtC emission energies. The TFY XAS, nonresonant XES, and VtC RXES data
      were all modeled within a density functional theory approach. While the TFY XAS
      and nonresonant XES data are readily interpreted by theory, the VtC RXES cannot
      be reproduced within such a simplified model. Nonetheless, dramatic changes in
      the experimental spectra are observed that have the potential to further the
      information content and selectivity of XAS. Potential applications and required
      theoretical developments are discussed. 

PMID- 24946008
TI  - Plasma processing for crystallization and densification of atomic layer
      deposition BaTiO3 thin films.
AB  - High-k, low leakage thin films are crucial components for dynamic random access
      memory (DRAM) capacitors with high storage density and a long storage lifetime.
      In this work, we demonstrate a method to increase the dielectric constant and
      decrease the leakage current density of atomic layer deposited BaTiO3 thin films
      at low process temperature (250  degrees C) using postdeposition remote oxygen
      plasma treatment. The dielectric constant increased from 51 (as-deposited) to 122
      (plasma-treated), and the leakage current density decreased by 1 order of
      magnitude. We ascribe such improvements to the crystallization and densification
      of the film induced by high-energy ion bombardments on the film surface during
      the plasma treatment. Plasma-induced crystallization presented in this work may
      have an immediate impact on fabricating and manufacturing DRAM capacitors due to
      its simplicity and compatibility with industrial standard thin film processes. 

PMID- 24946009
TI  - Co-ordinated regulation of the extracytoplasmic stress factor, sigmaE, with other
      Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific
      regulation of individual holoenzymes.
AB  - The E. coli alternative sigma factor, sigma(E) , transcribes genes required to
      maintain the cell envelope and is activated by conditions that destabilize the
      envelope. sigma(E) is also activated during entry into stationary phase in the
      absence of envelope stress by the alarmone (p)ppGpp. (p)ppGpp controls a large
      regulatory network, reducing expression of sigma(70) -dependent genes required
      for rapid growth and activating sigma(70) -dependent and alternative sigma factor
      dependent genes required for stress survival. The DksA protein often potentiates
      the effects of (p)ppGpp. Here we examine regulation of sigma(E) by (p)ppGpp and
      DksA following starvation for nutrients. We find that (p)ppGpp is required for
      increased sigma(E) activity under all conditions tested, but the requirement for
      DksA varies. DksA is required during amino acid starvation, but is dispensable
      during phosphate starvation. In contrast, regulation of sigma(S) is (p)ppGpp- and
      DksA-dependent under all conditions tested, while negative regulation of
      sigma(70) is DksA- but not (p)ppGpp-dependent during phosphate starvation, yet
      requires both factors during amino acid starvation. These findings suggest that
      the mechanism of transcriptional regulation by (p)ppGpp and/or DksA cannot yet be
      explained by a unifying model and is specific to individual promoters, individual
      holoenzymes, and specific starvation conditions. 

PMID- 24946010
TI  - The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p
      in papillary thyroid carcinoma progression.
AB  - Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid
      carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas
      that invade locally or metastasize are associated with a poor prognosis. We found
      that, during epithelial-mesenchymal transition (EMT) induced by transforming
      growth factor-beta1 (TGF-beta1), papillary thyroid carcinoma cells acquired
      increased cancer stem cell-like features and the transcription factor paired
      related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer,
      was markedly up-regulated. miR-146b-5p was also transiently up-regulated during
      EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell
      proliferation and invasion during TGF-beta1-induced EMT. We conclude that
      papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like
      features during TGF-beta1-induced EMT, that miR-146b-5p has a role in cell
      proliferation and invasion, and that PRRX1 plays an important role in papillary
      thyroid carcinoma EMT and disease progression. 

PMID- 24946012
TI  - An investigation of broiler caecal Campylobacter counts at first and second
      thinning.
AB  - AIMS: The objectives of this study were the following: (i) to investigate if
      Campylobacter negative flocks at first thinning remain negative at second
      thinning; (ii) to determine if the caecal counts in birds infected during first
      thinning remain lower than in birds that were positive at first thinning; and
      (iii) to determine if reducing the time between first and second thinning to a
      maximum of 4 days would reduce both the incidence and prevalence of broiler
      caecal contamination. METHODS AND RESULTS: Twenty-two flocks were tested at first
      and second thinning using ISO methodologies. Of the 14 that had a 4-day duration
      between first and second thinning, nine flocks were Campylobacter negative at
      first thinning. By second thinning, all 14 flocks were positive and Campylobacter
      counts ranged from 5.5 to 6.6 log(10) CFU g(-1) regardless of the status at first
      thinning. The other eight flocks were all Campylobacter positive at first
      thinning with counts ranging from 0.8 to 6.1 log(10) CFU g(-1) which increased to
      5.1 to 6.9 log(10) CFU g(-1) by second thinning (3-10 days). PCR speciation and
      MLST genotyping suggested the majority of isolates were Camp. jejuni belonging to
      STs 257, 814, 6763 and 6764. CONCLUSIONS: It was concluded that; thinning
      introduces Campylobacter into broiler flocks; caecal counts in birds at second
      thinning are similar, regardless of flock status at first thinning and reducing
      the time between first and second thinning to a maximum of 4 days is not an
      effective control strategy. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      informs Campylobacter control strategy at primary production, suggesting all post
      first thinning broilers should be treated as 'high risk' regardless of
      Campylobacter status at first thinning or duration between first and second
      thinning.

PMID- 24946013
TI  - Estimation of surface heat flux and temperature distributions in a multilayer
      tissue based on the hyperbolic model of heat conduction.
AB  - In this study, an inverse algorithm based on the conjugate gradient method and
      the discrepancy principle is applied to solve the inverse hyperbolic heat
      conduction problem in estimating the unknown time-dependent surface heat flux in
      a skin tissue, which is stratified into epidermis, dermis, and subcutaneous
      layers, from the temperature measurements taken within the medium. Subsequently,
      the temperature distributions in the tissue can be calculated as well. The
      concept of finite heat propagation velocity is applied to the modeling of the
      bioheat transfer problem. The inverse solutions will be justified based on the
      numerical experiments in which two different heat flux distributions are to be
      determined. The temperature data obtained from the direct problem are used to
      simulate the temperature measurements. The influence of measurement errors on the
      precision of the estimated results is also investigated. Results show that an
      excellent estimation on the time-dependent surface heat flux can be obtained for
      the test cases considered in this study. 

PMID- 24946011
TI  - Nonhematopoietic beta-Arrestin-1 inhibits inflammation in a murine model of
      polymicrobial sepsis.
AB  - beta-Arrestin-1 (betaArr1), a scaffolding protein critical in G-protein coupled
      receptor desensitization has more recently been found to be important in the
      pathogenesis of various inflammatory diseases. We sought to understand the role
      of betaArr1 in sepsis pathogenesis using a mouse model of polymicrobial sepsis.
      Although in previous studies we established that betaArr1 deficiency protects
      mice from endotoxemia, here we demonstrate that the absence of betaArr1
      remarkably renders mice more susceptible to mortality in polymicrobial sepsis. In
      accordance with the mortality pattern, early production of inflammatory mediators
      was markedly enhanced in betaArr1 knockout mice systemically and locally in
      various organs. In addition, enhanced inflammation in the heart was associated
      with increased NFkappaB activation. Compared to these effects, immune cell
      infiltration, thymic apoptosis, and immune suppression during polymicrobial
      sepsis were unaffected by a deficiency of betaArr1. Additionally, enhanced
      inflammation and consequent higher mortality were not observed in heterozygous
      mice, suggesting that one allele of betaArr1 was sufficient for this protective
      negative regulatory role. We further demonstrate that, unexpectedly, betaArr1 in
      nonhematopoietic cells is critical and sufficient for inhibiting sepsis-induced
      inflammation, whereas hematopoietic betaArr1 is likely redundant. Taken together,
      our results reveal a novel and previously unrecognized negative regulatory role
      of the nonhematopoietic betaArr1 in sepsis-induced inflammation. 

PMID- 24946014
TI  - An integrated study of natural hydroxyapatite-induced osteogenic differentiation
      of mesenchymal stem cells using transcriptomics, proteomics and microRNA
      analyses.
AB  - This work combined transcriptomics, proteomics, and microRNA (miRNA) analyses to
      elucidate the mechanism of natural hydroxyapatite (NHA)-induced osteogenic
      differentiation of mesenchymal stem cells (MSCs). First, NHA powder was obtained
      from pig bones and fabricated into disc-shaped samples. Subsequently, the
      proliferation and osteogenic differentiation of MSCs cultured on NHA were
      investigated. Then, proteomics was employed to detect the protein expression
      profiles of MSCs cultured on NHA, and the effect of NHA on MSCs was analyzed
      through an integrated pathway analysis (including proteomics and previous
      transcriptomics data) in which specific NHA-induced differentiation pathways were
      analyzed. The pathway nodes with expression data at both the mRNA and protein
      levels (mRNA-protein pairs) were filtered in differentiation-related pathways.
      miRNAs corresponding to these target mRNA-protein pairs were predicted, screened
      and tested, and the regulatory effects of miRNAs on mRNA-protein pairs were
      analyzed. Finally, the NHA-induced osteogenic pathways were verified. The results
      of an MTT assay and alkaline phosphatase (ALP) staining showed that the cell
      proliferation rate decreased and the osteogenic performance improved in the
      presence of NHA. By integrating transcriptomics and proteomics, the genes and
      proteins involved in 89 pathways were shown to be differentially expressed. Among
      them, 5 differentiation-associated pathways, in which 9 miRNAs and 8 regulated
      target mRNA-protein zby inhibiting the target mRNA-protein pair HSPA8 in the MAPK
      signaling pathway, and miR-26a and miR-26b might inhibit adipogenic
      differentiation by repressing the target mRNA-protein pair HMGA1 in the
      adipogenesis pathway. A verification experiment for the osteogenic pathway
      indicated that the ERK1/2 or JNK MAPK pathways might play an important role in
      NHA-induced osteogenic differentiation. In conclusion, NHA affected MSCs at both
      the transcriptional and translational levels, and MSC osteogenic differentiation
      eventually occurred through the MAPK and adipogenesis pathways, in which miRNAs
      and target mRNAs/proteins participated cooperatively. 

PMID- 24946015
TI  - Recommendations for safety pharmacology evaluations of oligonucleotide-based
      therapeutics.
AB  - This document was prepared by the Safety Pharmacology Subcommittee of the
      Oligonucleotide Safety Working Group (OSWG), a group of industry and regulatory
      scientists involved in the development and regulation of therapeutic
      oligonucleotides. The mission of the Subcommittee was to develop scientific
      recommendations for the industry regarding the appropriate scope and strategies
      for safety pharmacology evaluations of oligonucleotides (ONs). These
      recommendations are the consensus opinion of the Subcommittee and do not
      necessarily reflect the current expectations of regulatory authorities. 1) Safety
      pharmacology testing, as described in the International Conference on
      Harmonisation (ICH) S7 guidance, is as applicable to ONs as it is to small
      molecule drugs and biotherapeutics. 2) Study design considerations for ONs are
      similar to those for other classes of drugs. In general, as with other
      therapeutics, studies should evaluate the drug product administered via the
      clinical route. Species selection should ideally consider relevance of the model
      with regard to the endpoints of interest, pharmacological responsiveness, and
      continuity with the nonclinical development program. 3) Evaluation of potential
      effects in the core battery (cardiovascular, central nervous, and respiratory
      systems) is recommended. In general: a. In vitro human ether-a-go-go-related gene
      (hERG) testing does not provide any specific value and is not warranted. b.
      Emphasis should be placed on in vivo evaluation of cardiovascular function,
      typically in nonhuman primates (NHPs). c. Due to the low level of concern,
      neurologic and respiratory function can be assessed concurrently with
      cardiovascular safety pharmacology evaluation in NHPs, within repeat-dose
      toxicity studies, or as stand-alone studies. In the latter case, rodents are most
      commonly used. 4) Other dedicated safety pharmacology studies, beyond the core
      battery, may have limited value for ONs. Although ONs can accumulate in the
      kidney and liver, evaluation of functional changes in these organs, as well as
      gastrointestinal (GI) and unintended "pro-inflammatory" effects, may be best
      evaluated during repeat-dose toxicity studies. Broad receptor- or ligand-binding
      profiling has not historically been informative for most ON subclasses, but may
      have value for investigative purposes.

PMID- 24946017
TI  - Label-free glycopeptide quantification for biomarker discovery in human sera.
AB  - Glycan moieties of glycoproteins modulate many biological processes in mammals,
      such as immune response, inflammation, and cell signaling. Numerous studies show
      that many human diseases are correlated with quantitative alteration of protein
      glycosylation. In some cases, these changes can occur for certain types of
      glycans over specific sites in a glycoprotein rather than on the global abundance
      of the glycoprotein. Conventional analytical techniques that analyze the
      abundance of glycans cleaved from glycoproteins cannot reveal these subtle
      effects. Here we present a novel statistical method to quantify the site-specific
      glycosylation of glycoproteins in complex samples using label-free mass
      spectrometric techniques. Abundance variations between sites of a glycoprotein as
      well as different glycoforms, that is, glycopeptides with different glycans
      attached to the same site, can be detected using these techniques. We applied our
      method to an esophageal cancer study based on blood serum samples from cancer
      patients in an attempt to detect potential biomarkers of site-specific N-linked
      glycosylation. A few glycoproteins, including vitronectin, showed significantly
      different site-specific glycosylations within cancer/control samples, indicating
      that our method is ready to be used for the discovery of glycosylated biomarkers.

PMID- 24946018
TI  - Individual prediction regions for multivariate longitudinal data with small
      samples.
AB  - Follow-up is more and more used in medicine/doping control to identify abnormal
      results in an individual. Currently, follow-ups are mostly carried out variable
      by variable using "reference intervals" that contain the values observable in
      100(1-alpha)% of healthy/undoped individuals. Observations of the evolution of
      the variables over time in a sample of N healthy/undoped individuals, allows
      these reference intervals to be individualized by taking into account the
      possible effect of covariables and some previous observations of these variables
      obtained when the individual was healthy/undoped. For each variable these
      individualized intervals should contain 100(1-alpha)% of observable values
      compatible with previous observed values in this individual. General methods to
      build these intervals are available, but they allow only a variable by variable
      follow-up whatever the possible correlations over time between them. In this
      article, we propose a general method to jointly follow-up several correlated
      variables over time. This methodology relies on a multivariate linear mixed
      effects model. We first provide a method to estimate the model's parameters. In
      an asymptotic framework (N large enough), we then derive a (1-alpha)
      individualized prediction region. Sometimes, the sample size N is not large
      enough for the asymptotic framework to give a reasonable prediction region. It is
      for this reason, we propose and compare three different prediction regions that
      should behave better for small N. Finally, the whole methodology is illustrated
      by the follow-up of kidney insufficiency in cats.

PMID- 24946016
TI  - Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and
      Freud-1.
AB  - The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two
      of its key transcriptional modulators, NUDR and Freud-1, was examined in the
      prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory
      bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild
      stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most
      widespread changes, with significant reduction in both mRNA and protein levels of
      NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud
      1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1
      and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor,
      Freud-1 and NUDR mRNA's but not protein were reduced. In PS rats PFC 5-HT1A
      receptor protein was reduced more in females than males; while in Hp Freud-1
      protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5
      HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein
      levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced.
      Overall, CMS and stress during pregnancy produced the most salient changes in 5
      HT1A receptor and transcription factor expression, suggesting a primary role for
      altered transcription factor expression in chronic regulation of 5-HT1A receptor
      expression. By contrast, OB (in males) and PS (in females) produced gender
      specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for
      post-transcriptional regulation. These and previous data suggest that chronic
      stress might be a key regulator of NUDR/Freud-1 gene expression. 

PMID- 24946020
TI  - Wetting transitions within membrane compartments.
AB  - A biomimetic membrane in contact with several aqueous phases is theoretically
      studied using a combination of Helfrich curvature elasticity theory for fluid
      membranes and self-consistent field theory for polymers in solutions. Two phases
      that are thermodynamically formed by phase separation of aqueous solutions, as
      well as stable and metastable shapes of fluid vesicles, have been observed. The
      wetting transitions from complete to partial wetting and to complete dewetting
      are identified within a membrane compartment. The dependences of wetting
      transitions on material parameters, such as the intrinsic contact angles thetain,
      the interaction strengths between the polymers chialphabeta and between the
      membrane and the polymer etap, and impermeability of the membrane to the enclosed
      polymers zetap, are investigated. For a given chialphabeta, impermeability zetap
      and affinity to the membrane etap, thetain is found to be a constant and
      independent of the reduced volume of vesicles and the volume fraction of two
      phases. 

PMID- 24946021
TI  - The effects of renal impairment on the pharmacokinetics, safety, and tolerability
      of naloxegol.
AB  - The impact of renal impairment on the pharmacokinetics of a 25-mg oral dose of
      naloxegol was examined in patients with renal impairment classified as moderate,
      severe, or end-stage renal disease (ESRD) and compared with healthy subjects (n =
      8/group). Geometric mean area under the plasma concentration-time curve (AUC) was
      increased in patients with moderate (1.7-fold) or severe (2.2-fold) impairment,
      and maximum plasma concentrations (Cmax ) were elevated in patients with moderate
      (1.1-fold) or severe (1.8-fold) impairment. These findings were driven by higher
      exposures in two patients in each of the moderate and severe impairment groups;
      exposures in all other patients were similar to the control group. Overall
      exposures in ESRD patients were similar and Cmax was 29% lower versus normal
      subjects. Renal impairment minimally affected other plasma pharmacokinetic
      parameters. As renal clearance was a minor component of total clearance, exposure
      to naloxegol was unaffected by the degree of renal impairment, with no
      correlation between either AUC or Cmax and estimated glomerular filtration rate
      (eGFR). Hemodialysis was an ineffective means to remove naloxegol. Naloxegol was
      generally well tolerated in all groups. Renal impairment could adversely affect
      clearance by hepatic and gut metabolism, resulting in the increased exposures
      observed in outliers of the moderate and severe renal impairment groups. 

PMID- 24946022
TI  - Wide-gene expression analysis of lipid-relevant genes in nutritionally challenged
      gilthead sea bream (Sparus aurata).
AB  - Disturbances of lipid metabolism are a major problem in livestock fish and the
      present study analysed the different tissue expression patterns and regulations
      of 40 lipid-relevant genes in gilthead sea bream. Nineteen sequences, including
      fatty acid elongases (4), phospholipases (7), acylglycerol lipases (8) and lipase
      maturating enzymes (1), were new for gilthead sea bream (GenBank, JX975700
      JX975718JX975700JX975701JX975702JX975703JX975704JX975705JX975706JX975707JX975708J
      975709JX975710JX975711JX975712JX975713JX975714JX975715JX975716JX975717JX975718).
      Up to six different lipase-related enzymes were highly expressed in adipose
      tissue and liver, which also showed a high expression level of Delta6 and Delta9
      desaturases. In the brain, the greatest gene expression level was achieved by the
      very long chain fatty acid elongation 1, along with relatively high levels of
      Delta9 desaturases and the phospholipase retinoic acid receptor responder. These
      two enzymes were also expressed at a high level in white skeletal muscle, which
      also shared a high expression of lipid oxidative enzymes. An overall down
      regulation trend was observed in liver and adipose tissue in response to fasting
      following the depletion of lipid stores. The white skeletal muscle of fasted fish
      showed a strong down-regulation of Delta9 desaturases in conjunction with a
      consistent up-regulation of the "lipolytic machinery" including key enzymes of
      tissue fatty acid uptake and mitochondrial fatty acid transport and oxidation. In
      contrast, the gene expression profile of the brain remained almost unaltered in
      fasted fish, which highlights the different tissue plasticity of lipid-related
      genes. Taken together, these findings provide new fish genomic resources and
      contribute to define the most informative set of lipid-relevant genes for a given
      tissue and physiological condition in gilthead sea bream. 

PMID- 24946023
TI  - Investigation of sensitivity, specificity and accuracy of Tetra primer ARMS PCR
      method in comparison with conventional ARMS PCR, based on sequencing technique
      outcomes in IVS-II-I genotyping of beta thalassemia patients.
AB  - PURPOSE: Beta thalassemia is one of the most important hematic diseases all
      around the world and solving the problems caused by this abnormality is strongly
      dependent on precise detection and reliable screening of high-risk couples. The
      aim of our study was the investigation of sensitivity, specificity and accuracy
      of Tetra primer ARMS PCR method comparing with conventional ARMS PCR, based on
      sequencing technique outcomes for genotyping of IVS-II-I mutation in beta
      thalassemia patients. METHODS: Fifty seven samples including two homozygote, 49
      heterozygote and 6 normal specimens were analyzed by Tetra primer ARMS PCR and
      conventional ARMS PCR methods. DNA was extracted by the standard method of
      salting out for leukocyte genomic DNA extraction of blood specimens and a high
      pure PCR template preparation kit was used for DNA purification of CVS samples.
      The results obtained by Tetra primer ARMS PCR and conventional ARMS PCR methods
      were compared with gold standard technique, i.e. sequencing. RESULTS: All three
      parameters including specificity, sensitivity and accuracy were 100% for Tetra
      primer ARMS PCR method, while they were 100%, 92.45% and 92.7% for conventional
      ARMS PCR technique respectively. Comparing with Tetra primer ARMS PCR which
      represented 100% agreement with sequencing method, conventional ARMS PCR
      technique only showed 47.1% agreement, because of 4 discordant results.
      CONCLUSION: Tetra primer ARMS PCR method is an almost reliable, sensitive and
      accurate technique and it is suggested that it can be used as a complementary
      method for diagnostic cases instead of conventional ARMS PCR method. This
      suggestion originated with perfect rate of agreement between outcomes of
      sequencing method, as a gold standard method of detecting the mutations, and
      Tetra primer ARMS PCR technique comparing with conventional ARMS PCR method.

PMID- 24946024
TI  - Bi-level Positive Airway Pressure (BiPAP) with standard exhalation valve does not
      improve maximum exercise capacity in patients with COPD.
AB  - BACKGROUND: Although BiPAP has been used as an adjunct to exercise, little is
      know about its effect on exercise in COPD. We aimed to evaluate the acute effect
      of BiPAP delivered with a standard valve (Vision, Respironics), compared to no
      assist, on exercise capacity in individuals with COPD. METHODS: Peak exercise
      workload (WLpeak), dyspnea (Borg), end-expiratory lung volume (EELV), tidal
      volume (VT), minute ventilation (VE), O2 uptake (VO2), and CO2 production (VCO2)
      were assessed in 10 COPD patients (FEV1 53 +/- 22% pred) during three symptom
      limited bicycle exercise tests while breathing i) without a ventilator (noPS),
      ii) with a pressure support (PS) of 0 cm H2O (PS0; IPAP & EPAP 4 cm H2O) and iii)
      PS of 10 cm H2O (PS10; IPAP 14 & EPAP 4 cm H2O) on separate days using a
      randomized crossover design. RESULTS: WLpeak was significantly lower with PS10
      (33 +/- 16) and PS0 (30.5 +/- 13) than noPS (43 +/- 19) (p < 0.001). Dyspnea at
      peak exercise was similar with noPS, PS0 and PS10; at isoload it was lower with
      noPS compared to PS10 and PS0 (p < 0.01). VT and VE were highest with PS10 and
      lowest with noPS both at peak exercise and isoload (p < 0.001). EELV was similar
      at peak exercise with all three conditions. VO2 and VCO2 were greater with PS10
      and PS0 than noPS (p < 0.001), both at peak exercise and isoload. CONCLUSION: Use
      of BiPAP with a standard exhalation valve during exercise increases VT and VE at
      the expense of augmenting VCO2 and dyspnea, which in turns reduces WLpeak in COPD
      patients.

PMID- 24946019
TI  - Drosophila as a model for the two myeloid blood cell systems in vertebrates.
AB  - Fish, mice, and humans rely on two coexisting myeloid blood cell systems. One is
      sustained by hematopoietic progenitor cells, which reside in specialized
      microenvironments (niches) in hematopoietic organs and give rise to cells of the
      monocyte lineage. The other system corresponds to the independent lineage of self
      renewing tissue macrophages, which colonize organs during embryonic development
      and are maintained during later life by proliferation in local tissue
      microenvironments. However, little is known about the nature of these
      microenvironments and their regulation. Moreover, many vertebrate tissues contain
      a mix of both tissue-resident and monocyte-derived macrophages, posing a
      challenge to the study of lineage-specific regulatory mechanisms and function.
      This review highlights how research in the simple model organism Drosophila
      melanogaster can address many of these outstanding questions in the field.
      Drawing parallels between hematopoiesis in Drosophila and vertebrates, we
      illustrate the evolutionary conservation of the two myeloid systems across animal
      phyla. Much like vertebrates, Drosophila possesses a lineage of self-renewing
      tissue-resident macrophages, which we refer to as tissue hemocytes, as well as a
      "definitive" lineage of macrophages that derive from hematopoiesis in the
      progenitor-based lymph gland. We summarize key findings from Drosophila
      hematopoiesis that illustrate how local microenvironments, systemic signals,
      immune challenges, and nervous inputs regulate adaptive responses of tissue
      resident macrophages and progenitor-based hematopoiesis to maximize fitness of
      the animal. 

PMID- 24946025
TI  - Do the first, second and third trimester maternal serum hepcidin concentrations
      clarify obstetric complications?
AB  - OBJECTIVE: To evaluate whether first, second, and third-trimester maternal serum
      hepcidin levels are different in pregnancies with and without adverse pregnancy
      outcomes (APO). METHODS: A 165 nullipar pregnant women were included in this
      prospective cohort study. Serum hepcidin, ferritin, IL-6, C-reactive protein
      (CRP) and Hb values were measured at 11-14, 24-28, and 30-34 weeks of gestation.
      The relation between these parameters and APO and neonatal outcomes were
      investigated. Preterm delivery, intrauterine growth restriction, pre-eclampsia,
      gestational hypertension and placental abruption were determined as adverse
      pregnancy outcomes. RESULTS: The risk of APO was three times higher in women with
      high IL-6 levels in the second trimester. High hepcidin levels in the second
      trimester were associated with a 1.6 times increased risk of APO. Newborns of
      women with high IL-6 levels in the third trimester had a 1.6-fold increased risk
      of neonatal complications. High ferritin levels in the third trimester were
      associated with minimally increased risk of neonatal complications. CONCLUSIONS:
      Mean serum hepcidin levels were similar in all pregnant women, however, elevated
      second trimester serum hepcidin and IL-6 levels were associated with a higher
      risk of APO and high third trimester hepcidin, ferritin and IL-6 levels were
      associated with higher risk of neonatal complications.

PMID- 24946026
TI  - Impact of operator experience on the variability of fetal lung volume estimation
      by 3D-ultrasound (VOCAL) and magnetic resonance imaging in fetuses with
      congenital diaphragmatic hernia.
AB  - OBJECTIVE: To evaluate the impact of operator experience in volumetric
      measurements on intra- and inter-observer variability of lung volume estimation
      by 3-dimensional (3D) ultrasound and magnetic resonance imaging (MRI) in fetuses
      with congenital diaphragmatic hernia (CDH). METHODS: We conducted a retrospective
      single-center study. Total fetal lung volume (TFLV) was measured twice using 52
      stored 3D-ultrasound volumes and 52 corresponding MRI exams by a fetal medicine
      specialist with no experience in volumetric measurements and two operators
      experienced in the respective techniques. Bland-Altman analysis was performed to
      evaluate intra- and inter-observer variability. RESULTS: Measurements of TFLV by
      3D-ultrasound showed higher intra-observer variability compared with MRI
      irrespective of operator experience, with narrower 95% limits of agreement on MRI
      as compared with ultrasound measurements. Similarly, 3D-ultrasound showed higher
      inter-observer variability as compared with MRI. Finally the 95% limits of
      agreement at ultrasound were quite comparable for intra-observer variability
      between the experienced and the inexperienced operator. CONCLUSION: Our study
      shows that operator experience has an impact on the variability of TFLV and, in
      the absence of experience in volumetric measurements, estimation of TFLV in
      fetuses with CDH by 3D-ultrasound shows higher variability than MRI measurements,
      but even in experienced hands variability is greater for 3D-ultrasound.

PMID- 24946027
TI  - Health status assessment through an integrative biomarker approach in mussels of
      different ages with a different history of exposure to the Prestige oil spill.
AB  - A battery of cell and tissue-level biomarkers was applied in mussels of 6 size
      classes collected from Galicia and the Basque coast in summer 2007 in an attempt
      to examine the health status of individuals affected as adults (mature before
      2003), affected during their developmental or juvenile stages (2003-2004
      offspring), or not directly affected by the Prestige oil spill (POS) exposure
      (presumably 2005-2006 offspring). This battery of biomarkers was akin to those
      formerly applied on mussels of 3.5-4.5 cm shell length for which there exist
      biomarker reference values in the studied geographical areas. The cause-effect
      relationship between biological responses and the different history of exposure
      to POS fuel oil was intricate for different reasons: (a) growth rate was
      dissimilar in mussels of the two studied localities and much lower than expected,
      (b) a chronological basis could not be directly associated to POS events (all
      mussels except the smallest from Galicia had been subjected to the direct POS
      impact at one or another stage of their life-cycle); and (c) some biomarkers and
      histopathology seemingly depended on size/age irrespectively of the locality and
      the POS chronology. As a whole, the present study gives a very useful set of
      reference values of biomarkers obtained for Mytilus galloprovincialis of
      different size-classes. Finally, it is recommended that Mussel Watch programmes
      should be designed by standardising the age of the sentinel mussels rather than
      their size, especially if the programme covers large or diverse geographical
      areas, if long-term trends are relevant or if significant pollution effects on
      growth are expected.

PMID- 24946028
TI  - Simulation of spatial and temporal distributions of non-point source pollution
      load in the Three Gorges Reservoir Region.
AB  - Non-point source (NPS) pollution has become the largest threat to water quality
      in recent years. Major pollutants, particularly from agricultural activities,
      which include nitrogen, phosphorus and sediment that have been released into
      aquatic environments, have caused a range of problems in the Three Gorges
      Reservoir Region (TGRR), China. It is necessary to identify the spatial and
      temporal distributions of NPS pollutants and the highly polluted areas for the
      purpose of watershed management. In this study, the NPS pollutant load was
      simulated using the Soil and Water Assessment Tool (SWAT) and the small-scale
      watershed extended method (SWEM). The simulation results for four typical small
      catchments were extended to the entire watershed leading to estimates of the NPS
      load from 2001 to 2009. The results demonstrated that the NPS pollution load in
      the western area was the highest and that agricultural land was the primary
      pollutant source. The similar annual variation trends of runoff and sediment
      loads demonstrated that the sediment load was closely related to runoff. The
      loads of total nitrogen (TN) and total phosphorus (TP) were relatively stable
      from 2001 to 2007, except for high loads in 2006. The increase in pollution
      source strength was an important reason for the significant upward trend of TN
      and TP loads from 2008 to 2009. The rainfall from April to October contributed to
      the largest amount of runoff, sediment and nutrient loads for the year. The NPS
      load intensities in each sub-basin reveal large variations in the spatial
      distribution of different pollutants. It was shown that the temporal and spatial
      distributions of pollutant loads were positively correlated with the annual
      rainfall amounts and with human activities. Furthermore, this finding illustrates
      that conservation practices and nutrient management should be implemented in
      specific sites during special periods for the purpose of NPS pollution control in
      the TGRR. 

PMID- 24946029
TI  - Detection of emerging contaminants (UV filters, UV stabilizers and musks) in
      marine mussels from Portuguese coast by QuEChERS extraction and GC-MS/MS.
AB  - The UV filters and musk fragrances have come into focus because these compounds
      are contained and increasingly used not only in sunscreen products but also in
      many products of daily use, such as cosmetics, skin creams, plastics or varnish.
      In view of this, the main objective of the present work was to develop and
      validate a method for the determination of three UV filters, two UV stabilizers
      and four musks in mussel samples (Mytilus galloprovincialis). The procedure
      combined a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction
      method with an analysis by gas chromatography-tandem mass spectrometry (GC
      MS/MS). The methodology allowed the determination of target analytes at trace
      concentration levels (ng/g), with mean recoveries ranging from 91 to 112%. A
      monitoring study was conducted in four beaches in the Portuguese coast which are
      impacted by recreational activities and outflow of treated waste water effluents
      in rivers. The results are used to assess the occurrence of UV filters in
      comparison with UV stabilizers and musk fragrances which indicate other
      activities than bathing. 

PMID- 24946030
TI  - Incorporation of radiometric tracers in peat and implications for estimating
      accumulation rates.
AB  - Accurate dating of peat accumulation is essential for quantitatively
      reconstructing past changes in atmospheric metal deposition and carbon burial. By
      analyzing fallout radionuclides (210)Pb, (137)Cs, (241)Am, and (7)Be, and total
      Pb and Hg in 5 cores from two Swedish peatlands we addressed the consequence of
      estimating accumulation rates due to downwashing of atmospherically supplied
      elements within peat. The detection of (7)Be down to 18-20 cm for some cores, and
      the broad vertical distribution of (241)Am without a well-defined peak, suggest
      some downward transport by percolating rainwater and smearing of atmospherically
      deposited elements in the uppermost peat layers. Application of the CRS age-depth
      model leads to unrealistic peat mass accumulation rates (400-600 g m(-2) yr(-1)),
      and inaccurate estimates of past Pb and Hg deposition rates and trends, based on
      comparisons to deposition monitoring data (forest moss biomonitoring and wet
      deposition). After applying a newly proposed IP-CRS model that assumes a
      potential downward transport of (210)Pb through the uppermost peat layers, recent
      peat accumulation rates (200-300 g m(-2) yr(-1)) comparable to published values
      were obtained. Furthermore, the rates and temporal trends in Pb and Hg
      accumulation correspond more closely to monitoring data, although some off-set is
      still evident. We suggest that downwashing can be successfully traced using
      (7)Be, and if this information is incorporated into age-depth models, better
      calibration of peat records with monitoring data and better quantitative
      estimates of peat accumulation and past deposition are possible, although more
      work is needed to characterize how downwashing may vary between seasons or years.

PMID- 24946031
TI  - Assessment of combined electro-nanoremediation of molinate contaminated soil.
AB  - Molinate is a pesticide widely used, both in space and time, for weed control in
      rice paddies. Due to its water solubility and affinity to organic matter, it is a
      contaminant of concern in ground and surface waters, soils and sediments.
      Previous works have showed that molinate can be removed from soils through
      electrokinetic (EK) remediation. In this work, molinate degradation by zero
      valent iron nanoparticles (nZVI) was tested in soils for the first time. Soil is
      a highly complex matrix, and pollutant partitioning between soil and water and
      its degradation rates in different matrices is quite challenging. A system
      combining nZVI and EK was also set up in order to study the nanoparticles and
      molinate transport, as well as molinate degradation. Results showed that molinate
      could be degraded by nZVI in soils, even though the process is more time
      demanding and degradation percentages are lower than in an aqueous solution. This
      shows the importance of testing contaminant degradation, not only in aqueous
      solutions, but also in the soil-sorbed fraction. It was also found that soil type
      was the most significant factor influencing iron and molinate transport. The main
      advantage of the simultaneous use of both methods is the molinate degradation
      instead of its accumulation in the catholyte. 

PMID- 24946032
TI  - Photovoltaic powered ultraviolet and visible light-emitting diodes for
      sustainable point-of-use disinfection of drinking waters.
AB  - For many decades, populations in rural and remote developing regions will be
      unable to access centralised piped potable water supplies, and indeed,
      decentralised options may be more sustainable. Accordingly, improved household
      point-of-use (POU) disinfection technologies are urgently needed. Compared to
      alternatives, ultraviolet (UV) light disinfection is very attractive because of
      its efficacy against all pathogen groups and minimal operational consumables.
      Though mercury arc lamp technology is very efficient, it requires frequent lamp
      replacement, involves a toxic heavy metal, and their quartz envelopes and sleeves
      are expensive, fragile and require regular cleaning. An emerging alternative is
      semiconductor-based units where UV light emitting diodes (UV-LEDs) are powered by
      photovoltaics (PV). Our review charts the development of these two technologies,
      their current status, and challenges to their integration and POU application. It
      explores the themes of UV-C-LEDs, non-UV-C LED technology (e.g. UV-A, visible
      light, Advanced Oxidation), PV power supplies, PV/LED integration and POU
      suitability. While UV-C LED technology should mature in the next 10 years,
      research is also needed to address other unresolved barriers to in situ
      application as well as emerging research opportunities especially UV-A,
      photocatalyst/photosensitiser use and pulsed emission options.

PMID- 24946033
TI  - Environmental impact of recycling nutrients in human excreta to agriculture
      compared with enhanced wastewater treatment.
AB  - Human excreta are potential sources of plant nutrients, but are today usually
      considered a waste to be disposed of. The requirements on wastewater treatment
      plants (WWTPs) to remove nitrogen and phosphorus are increasing and to meet these
      requirements, more energy and chemicals are needed by WWTPs. Separating the
      nutrient-rich wastewater fractions at source and recycling them to agriculture as
      fertiliser is an alternative to removing them at the WWTP. This study used life
      cycle assessment methodology to compare the environmental impact of different
      scenarios for recycling the nutrients in the human excreta as fertiliser to
      arable land or removing them in an advanced WWTP. Three scenarios were assessed.
      In blackwater scenario, blackwater was source-separated and used as fertiliser.
      In urine scenario, the urine fraction was source-separated and used as fertiliser
      and the faecal water treated in an advanced WWTP. In NP scenario, chemical
      fertiliser was used as fertiliser and the toilet water treated in an advanced
      WWTP. The emissions from the WWTP were the same for all scenarios. This was
      fulfilled by the enhanced reduction in the WWTP fully removing the nutrients from
      the excreta that were not source-separated in the NP and urine scenarios.
      Recycling source-separated wastewater fractions as fertilisers in agriculture
      proved efficient for conserving energy and decreasing global warming potential
      (GWP). However, the blackwater and urine scenarios had a higher impact on
      potential eutrophication and potential acidification than the WWTP-chemical
      fertiliser scenario, due to large impacts by the ammonia emitted from storage and
      after spreading of the fertilisers. The cadmium input to the arable soil was very
      small with urine fertiliser. Source separation and recycling of excreta fractions
      as fertiliser thus has potential for saving energy and decreasing GWP emissions
      associated with wastewater management. However, for improved sustainability, the
      emissions from storage and after spreading of these fertilisers must decrease. 

PMID- 24946034
TI  - Composition of dissolved organic nitrogen in rivers associated with wetlands.
AB  - As basic information for assessing reactivity and functionality of wetland
      associated dissolved organic matter (DOM) based on their composition and
      structural properties, chemical characteristics of N in ultrafiltered DOM (UDON;
      >1 kD) isolated from wetland-associated rivers in three climates (cool-temperate,
      Hokkaido, Japan; sub-tropical, Florida, USA; tropical, Sarawak, Malaysia) were
      investigated. The UDON was isolated during dry and wet seasons, or during spring,
      summer, and autumn. The proportion of UDON present as humic substances, which was
      estimated as the DAX-8 adsorbed fraction, ranged from 47 to 91%, with larger
      values in the Sarawak than at the other sites. The yield of hydrolyzable amino
      acid N ranged 1.24 to 7.01 mg g(-1), which correlated positively to the total N
      content of UDOM and tended to be larger in the order of Florida>Hokkaido>Sarawak
      samples. X-ray photoelectron N1s spectra of UDON showed a strong negative
      correlation between the relative abundances of amide/peptide N and primary amine
      N. The relative abundances of amide/peptide N and primary amine N in the Sarawak
      samples were smaller (70-76%) and larger (20-23%) respectively compared to those
      (80-88% and 4-9%) in the Florida and Hokkaido samples. Assuming terminal amino
      groups and amide N of peptides as major constituents of primary amine N and
      amide/peptide N, respectively, the average molecular weight of peptides was
      smaller in the Sarawak samples than that in the Florida and Hokkaido samples.
      Seasonal variations in UDON composition were scarce in the Sarawak and Florida
      samples, whereas the distribution of humic substance-N and nonhumic substance-N
      and compositions of amino acids and N functional groups showed a clear
      seasonality in the Hokkaido samples. While aromatic N increased from spring to
      autumn, contributions from fresh proteinaceous materials were also enhanced
      during autumn, resulting in the highest N content of UDOM for this season.

PMID- 24946036
TI  - Variability of metabolite levels is linked to differential metabolic pathways in
      Arabidopsis's responses to abiotic stresses.
AB  - Constraint-based approaches have been used for integrating data in large-scale
      metabolic networks to obtain insights into metabolism of various organisms. Due
      to the underlying steady-state assumption, these approaches are usually not
      suited for making predictions about metabolite levels. Here, we ask whether we
      can make inferences about the variability of metabolite levels from a constraint
      based analysis based on the integration of transcriptomics data. To this end, we
      analyze time-resolved transcriptomics and metabolomics data from Arabidopsis
      thaliana under a set of eight different light and temperature conditions. In a
      previous study, the gene expression data have already been integrated in a genome
      scale metabolic network to predict pathways, termed modulators and sustainers,
      which are differentially regulated with respect to a biochemically meaningful
      data-driven null model. Here, we present a follow-up analysis which bridges the
      gap between flux- and metabolite-centric methods. One of our main findings
      demonstrates that under certain environmental conditions, the levels of
      metabolites acting as substrates in modulators or sustainers show significantly
      lower temporal variations with respect to the remaining measured metabolites.
      This observation is discussed within the context of a systems-view of plasticity
      and robustness of metabolite contents and pathway fluxes. Our study paves the way
      for investigating the existence of similar principles in other species for which
      both genome-scale networks and high-throughput metabolomics data of high quality
      are becoming increasingly available. 

PMID- 24946038
TI  - Structural brain abnormalities in patients with inflammatory illness acquired
      following exposure to water-damaged buildings: a volumetric MRI study using
      NeuroQuant(r).
AB  - Executive cognitive and neurologic abnormalities are commonly seen in patients
      with a chronic inflammatory response syndrome (CIRS) acquired following exposure
      to the interior environment of water-damaged buildings (WDB), but a clear
      delineation of the physiologic or structural basis for these abnormalities has
      not been defined. Symptoms of affected patients routinely include headache,
      difficulty with recent memory, concentration, word finding, numbness, tingling,
      metallic taste and vertigo. Additionally, persistent proteomic abnormalities in
      inflammatory parameters that can alter permeability of the blood-brain barrier,
      such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB
      compared to controls, suggesting a consequent inflammatory injury to the central
      nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB
      cases compared to 5% of controls, as well as elevated lactate and depressed
      ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases.
      This study used the volumetric software program NeuroQuant(r) (NQ) to determine
      specific brain structure volumes in consecutive patients (N=17) seen in a medical
      clinic specializing in inflammatory illness. Each of these patients presented for
      evaluation of an illness thought to be associated with exposure to WDB, and
      received an MRI that was evaluated by NQ. When compared to those of a medical
      control group (N=18), statistically significant differences in brain structure
      proportions were seen for patients in both hemispheres of two of the eleven brain
      regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum.
      In addition, the left amygdala and right forebrain were also enlarged. These
      volumetric abnormalities, in conjunction with concurrent abnormalities in
      inflammatory markers, suggest a model for structural brain injury in "mold
      illness" based on increased permeability of the blood-brain barrier due to
      chronic, systemic inflammation. 

PMID- 24946040
TI  - Labor pain mechanisms.

PMID- 24946037
TI  - Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced
      seizures and cognitive deficits in rats.
AB  - The progression of epileptiform activity following soman (GD) exposure is
      characterized by a period of excessive cholinergic activity followed by excessive
      glutamatergic activity resulting in status epilepticus, which may lead to
      neuropathological damage and behavioral deficits. Caramiphen edisylate is an
      anticholinergic drug with antiglutamatergic properties, which conceptually may be
      a beneficial therapeutic approach to the treatment of nerve agent exposure. In
      the present study, rats were exposed to 1.2 LD50 GD or saline, treated with
      atropine sulfate (2mg/kg, im) and HI-6 (93.6mg/kg, im) 1min after GD exposure,
      and monitored for seizure activity. Rats were treated with diazepam (10mg/kg, sc)
      and caramiphen (0, 20 or 100mg/kg, im) 30min after seizure onset. Following GD
      exposure, performance was evaluated using a battery of behavioral tests to assess
      motor coordination and function, sensorimotor gating, and cognitive function.
      Caramiphen as adjunct to diazepam treatment attenuated GD-induced seizure
      activity, neuropathological damage, and cognitive deficits compared to diazepam
      alone, but did not attenuate the GD-induced sensorimotor gating impairment. These
      findings show that physiological, behavioral, and neuropathological effects of GD
      exposure can be attenuated by treatment with caramiphen as an adjunct to therapy,
      even if administration is delayed to 30min after seizure onset. 

PMID- 24946041
TI  - Accidental dural puncture and postdural puncture headache management.

PMID- 24946039
TI  - Prenatal tobacco exposure and response inhibition in school-aged children: an
      event-related potential study.
AB  - Prenatal cigarette smoke exposure (PCSE) has been linked to problems in
      behavioral inhibition and attention deficit hyperactivity disorder in children in
      several epidemiological studies. We used event-related potentials (ERPs) to
      examine the effects of PCSE on neural correlates of inhibitory control of
      behavior. In a prospective longitudinal study on child development in the
      Canadian Arctic, we assessed 186 Inuit children (mean age=11.3years) on a visual
      Go/No-go response inhibition paradigm. PCSE was assessed through maternal recall.
      Potential confounders were documented from a maternal interview, and exposure to
      neurotoxic environmental contaminants was assessed from umbilical cord and child
      blood samples. PCSE was not related to behavioral performance on this simple
      response inhibition task. Nevertheless, this exposure was associated with smaller
      amplitudes of the N2 and P3 components elicited by No-go stimuli, suggesting an
      impairment in the neural processes underlying response inhibition. Amplitude of
      the No-go P3 component was also inversely associated with behavioral measures of
      externalizing problems and hyperactivity/impulsivity in the classroom. This study
      is the first to report neurophysiological evidence of impaired response
      inhibition in school-aged children exposed to tobacco smoke in utero. Effects
      were found on ERP components associated with conflict processing and inhibition
      of a prepotent response, indicating neurophysiological deficits that may play a
      critical role in the attention and behavior problems observed in children with
      PCSE. 

PMID- 24946042
TI  - Obstetric-related neurological complications.

PMID- 24946043
TI  - Maternal embolism.

PMID- 24946044
TI  - Patient blood management in obstetrics.

PMID- 24946045
TI  - Labor epidural fever and chorioamnionitis.

PMID- 24946046
TI  - Comorbidities in obstetric anesthesia.

PMID- 24946047
TI  - Anesthetic considerations for the morbid obese parturient.

PMID- 24946050
TI  - Downregulation of tumor necrosis factor and other proinflammatory biomarkers by
      polyphenols.
AB  - Human tumor necrosis factor (TNF), first isolated by our group as an anticancer
      agent, has been now shown to be a primary mediator of inflammation. Till today 19
      different members of the TNF superfamily which interact with 29 different
      receptors, have been identified. Most members of this family exhibit pro
      inflammatory activities, in part through the activation of the transcription
      factor, nuclear factor-kappaB (NF-kappaB). Thus TNF and the related pro
      inflammatory cytokines have been shown to play a key role in most chronic
      diseases such as cancer, rheumatoid arthritis, cardiovascular diseases,
      psoriasis, neurologic diseases, Crohn's disease, and metabolic diseases.
      Therefore, agents that can modulate the TNF-mediated inflammatory pathways may
      have potential against these pro-inflammatory diseases. Although blockers of TNF
      alpha, such as infliximab (antibody against TNF-alpha), adalimumab (humanized
      antibody against TNF-alpha), and etanercept (soluble form of TNFR2) have been
      approved for human use, these blockers exhibit numerous side effects. In this
      review, we describe various plant-derived polyphenols that can suppress TNF-alpha
      activated inflammatory pathways both in vitro and in vivo. These polyphenols
      include curcumin, resveratrol, genistein, epigallocatechin gallate, flavopiridol,
      silymarin, emodin, morin isoliquiritigenin, naringenin, ellagic acid, apigenin,
      kaempferol, catechins, myricetin, xanthohumol, fisetin, vitexin, escin, mangostin
      and others. Thus these polyphenols are likely to have potential against various
      pro-inflammatory diseases. 

PMID- 24946052
TI  - Extracellular vesicles shed from gefitinib-resistant nonsmall cell lung cancer
      regulate the tumor microenvironment.
AB  - Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs),
      including gefitinib, are the first-line treatment of choice for nonsmall cell
      lung cancer patients who harbor activating EGFR mutations, however, acquired
      resistance to EGFR-TKIs is inevitable. The main objective of this study was to
      identify informative protein signatures of extracellular vesicles (EV) derived
      from gefitinib-resistant nonsmall cell lung cancer cells using proteomics
      analysis. Nano-LC-MS/MS analysis identified with high confidence (false discovery
      rate < 0.05, fold change >=2) 664 EV proteins enriched in PC9R cells, which are
      resistant to gefitinib due to EGFR T790M mutation. Computational analyses
      suggested components of several signal transduction mechanisms including the AKT
      (also PKB, protein kinase B)/mTOR (mechanistic target of rapamycin) pathway are
      overrepresented in EV from PC9R cells. Treatment of recipient cells with EV
      harvested from PC9R cells increased phosphorylation of signaling molecules, and
      enhanced proliferation, invasion, and drug resistance to gefitinib-induced
      apoptosis. Dose- and time-dependent pharmaceutical inhibition of AKT/mTOR pathway
      overcame drug resistance of PC9R cells and those of H1975 exhibiting EGFR T790M
      mutation. Our findings provide new insight into an oncogenic EV protein signature
      regulating tumor microenvironment, and will aid in the development of novel
      diagnostic strategies for prediction and assessment of gefitinib resistance. 

PMID- 24946051
TI  - Absorption, distribution, metabolism, and excretion of isoflavonoids after soy
      intake.
AB  - Soy is the major source of dietary exposure to isoflavonoids (IFLs). Accumulating
      evidence supports a role for soy and IFLs in the protection against many chronic
      diseases including cancer. After soy intake we found a biphasic IFL appearance
      pattern in plasma as well as in urine that we suggest to be due to IFL absorption
      in the small intestine (ca. 10%) during the first 2h after intake and IFL
      absorption in the large intestine (ca. 90%) 4-6 h after intake. While each IFL
      disappears from the circulation at different times excellent correlations between
      urinary and circulating IFL values were discovered and algorithms to convert
      urinary excretion values into circulating levels were established. We suggest the
      term 'apparent bioavailability' when using urinary data to describe IFL exposure.
      The IFL bioavailability was found to be influenced by gut bacteria, oral
      antibiotic treatment (OABX), and an individual's age and health status. While
      daidzein (DE) and genistein start to be absorbed minutes after intake, equol (EQ)
      appears in plasma only after a minimum of 8h following soy intake owing to the
      required transit time of DE to the colon where the conversion of DE to EQ takes
      place by intestinal microbiota. We have also shown that the apparent IFL
      bioavailability is higher in children than adults, higher in healthy versus non
      healthy individuals, and decreased in children but increased in adults during
      OABX. Finally, we propose to use a urinary EQ/DE ratio of 0.018 with a DE
      threshold to identify EQ producers. With this cutoff definition we observed that
      EQ production is inconsistent over time in 5-30% of both premenopausal and
      postmenopausal women.

PMID- 24946053
TI  - Cross-cultural adaptation of the Window to Hope: a psychological intervention to
      reduce hopelessness among U.S. veterans with traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To conduct a cross-cultural adaptation of Window to Hope
      (WtoH), a treatment to reduce hopelessness after traumatic brain injury (TBI),
      from the Australian civilian context to that of U.S. Veterans. RESEARCH DESIGN:
      Three-stage mixed-methods approach. METHODS: Stage 1: Consensus conference with
      stakeholders to revise the manual. Stage 2: Pilot study of the revised manual
      with US Veterans to examine acceptability, feasibility and fidelity. Stage 3:
      Review of results with consensus conference attendees and further revisions.
      RESULTS: Stage 1: Conference attendees reached 100% consensus regarding changes
      made to the manual. Stage 2: Qualitative results yielded themes that suggest that
      participants benefitted from the intervention and that multiple factors
      contributed to successful implementation (Narrative Evaluation of Intervention
      Interview, User Feedback Survey-Modified, Post-Treatment Interviews). Therapists
      achieved 100% treatment fidelity. Quantitative results from the Client
      Satisfaction Questionnaire-8 suggest that the intervention was acceptable. Stage
      3: The culturally adapted manual was finalized. CONCLUSIONS: RESULTS of this
      study suggest that the revised WtoH manual is acceptable and feasible. US
      therapists exhibited adherence to the protocol. The three-stage methodology was
      successfully employed to cross-culturally adapt an intervention that is well
      suited for a Phase II randomized controlled trial among US military Veterans.

PMID- 24946056
TI  - Effects of TIPS-functionalization and perhalogenation on the electronic, optical,
      and transport properties of angular and compact dibenzochrysene.
AB  - We report a systematic comparative study on dibenzo[b,def]chrysene (angular) and
      dibenzo[def,mno] chrysene (compact) polyaromatic hydrocarbons and their bis
      triisopropylsilylethynyl (TIPS)-functionalized and perhalogenated (F, Cl)
      counterparts. We used density functional theory (DFT) and time-dependent DFT to
      quantify the effects of morphology and chemical modifications on the electronic,
      optical, and transport properties. In particular, we compared electron affinity,
      ionization energy, fundamental gap, optical absorption, exciton binding energy,
      and reorganization energies for holes and electrons. For both TIPS
      functionalization and halogen substitutions, we found larger electron affinities
      (nearly tripled with perchlorination). Ionization energies are found to be
      reduced for TIPS-functionalization (by ~5%) and enhanced following halogen
      substitution (up to 17%). In both compact and angular dibenzochrysenes, the above
      trends reflect in a general reduction of the fundamental gap (up to 22%)
      following chemical modification. The effect of perhalogenation and TIPS
      functionalization is always to increase molecular reorganization energies for
      both holes and electrons. Concerning the optical properties, we observe a
      redshift of the optical onset in all cases; for TIPS-functionalized molecules, in
      particular, we additionally found a remarkable enhancement of the absorption in
      the visible region. 

PMID- 24946055
TI  - Discovery and optimization of small-molecule ligands for the CBP/p300
      bromodomains.
AB  - Small-molecule inhibitors that target bromodomains outside of the bromodomain and
      extra-terminal (BET) sub-family are lacking. Here, we describe highly potent and
      selective ligands for the bromodomain module of the human lysine acetyl
      transferase CBP/p300, developed from a series of 5-isoxazolyl-benzimidazoles. Our
      starting point was a fragment hit, which was optimized into a more potent and
      selective lead using parallel synthesis employing Suzuki couplings, benzimidazole
      forming reactions, and reductive aminations. The selectivity of the lead compound
      against other bromodomain family members was investigated using a thermal
      stability assay, which revealed some inhibition of the structurally related BET
      family members. To address the BET selectivity issue, X-ray crystal structures of
      the lead compound bound to the CREB binding protein (CBP) and the first
      bromodomain of BRD4 (BRD4(1)) were used to guide the design of more selective
      compounds. The crystal structures obtained revealed two distinct binding modes.
      By varying the aryl substitution pattern and developing conformationally
      constrained analogues, selectivity for CBP over BRD4(1) was increased. The
      optimized compound is highly potent (Kd = 21 nM) and selective, displaying 40
      fold selectivity over BRD4(1). Cellular activity was demonstrated using
      fluorescence recovery after photo-bleaching (FRAP) and a p53 reporter assay. The
      optimized compounds are cell-active and have nanomolar affinity for CBP/p300;
      therefore, they should be useful in studies investigating the biological roles of
      CBP and p300 and to validate the CBP and p300 bromodomains as therapeutic
      targets. 

PMID- 24946058
TI  - Editorial: safety and tolerability of rifaximin for IBS - more information is
      required.

PMID- 24946057
TI  - Functional brain networks formed using cross-sample entropy are scale free.
AB  - Over the previous decade, there has been an explosion of interest in network
      science, in general, and its application to the human brain, in particular. Most
      brain network investigations to date have used linear correlations (LinCorr)
      between brain areas to construct and then interpret brain networks. In this
      study, we applied an entropy-based method to establish functional connectivity
      between brain areas. This method is sensitive to both nonlinear and linear
      associations. The LinCorr-based and entropy-based techniques were applied to
      resting-state functional magnetic resonance imaging data from 10 subjects, and
      the resulting networks were compared. The networks derived from the entropy-based
      method exhibited power-law degree distributions. Moreover, the entropy-based
      networks had a higher clustering coefficient and a shorter path length compared
      with that of the LinCorr-based networks. While the LinCorr-based networks were
      assortative, with nodes with similar degrees preferentially connected, the
      entropy-based networks were disassortative, with high-degree hubs directly
      connected to low-degree nodes. It is likely that the differences in clustering
      and assortativity are due to "mega-hubs" in the entropy-based networks. These
      mega-hubs connect to a large majority of the nodes in the network. This is the
      first work clearly demonstrating differences between functional brain networks
      using linear and nonlinear techniques. The key finding is that the nonlinear
      technique produced networks with scale-free degree distributions. There remains
      debate among the neuroscience community as to whether human brains are scale
      free. These data support the argument that at least some aspects of the human
      brain are perhaps scale free.

PMID- 24946059
TI  - Editorial: IDASPHERE phase I trial for chemoembolisation of HCC.

PMID- 24946060
TI  - Editorial: safety and tolerability of rifaximin for IBS - more information is
      required; authors' reply.

PMID- 24946061
TI  - Editorial: IDASPHERE phase I trial for chemoembolisation for HCC - authors'
      reply: a necessary step for treatment optimisation and standardisation.

PMID- 24946062
TI  - Editorial: probiotics in NASH - more studies are needed.

PMID- 24946063
TI  - Editorial: probiotics in NASH - more studies are needed; authors' reply.

PMID- 24946064
TI  - Letter: is there a bi-directional relationship between depression and IBD?

PMID- 24946065
TI  - Letter: is there a bi-directional relationship between depression and IBD?
      Authors' reply.

PMID- 24946066
TI  - Letter: bile acid malabsorption - what is the prevalence in patients with chronic
      diarrhoea?

PMID- 24946067
TI  - Letter: bile acid diarrhoea is not a rare cause of diarrhoea in secondary care.

PMID- 24946068
TI  - Letter: estimating the cost-neutral price of sofosbuvir-based triple therapy for
      the treatment of naive patients with genotype 1 HCV infection in Italy.

PMID- 24946069
TI  - Letter: infliximab vs. adalimumab in treating ambulatory perianal fistulising
      Crohn's disease.

PMID- 24946070
TI  - Cissus quadrangularis extract attenuates hyperglycaemia-mediated oxidative stress
      in streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: Hyperglycaemia-mediated oxidative stress plays a major role in the
      progression of diabetic complications. This study was aimed at evaluating the
      beneficial effects of Cissus quadrangularis stem extract on antioxidant/oxidant
      status in diabetes mellitus. MATERIALS AND METHODS: The antioxidant activities of
      an ethyl acetate fraction of Cissus quadrangularis stem (CQSF) at three different
      doses (50, 100, and 200 mg/kg body weight) were evaluated in rats with
      experimentally induced diabetes. High performance liquid chromatography analysis
      was carried out to identify the active components present in the plant fraction.
      RESULTS: Induction of diabetes caused deleterious effects including
      hyperglycaemia, liver dysfunction, significant decline in antioxidants and
      elevated lipid peroxidation indices. C. quadrangularis supplementation
      significantly improved insulin sensitivity, reduced liver damage, and oxidative
      changes, and brought back the antioxidants towards normal. Histopathological
      analysis of the liver also reinforced our findings. Pronounced changes were
      observed at the doses 100 and 200 mg/kg body weight. In addition, high
      performance liquid chromatography analysis of C. quadrangularis fraction revealed
      the presence of quercetin. DISCUSSION: This study suggests an anti-diabetic
      potential of CQSF, mediated through the modulation of the antioxidant defence
      system. The ethyl acetate fraction of Cissus quadrangularis is rich in quercetin
      and this indicates that the supplementation of CQSF might be beneficial as a food
      supplement for the attenuation of diabetic complications.

PMID- 24946072
TI  - Increased CRF mRNA expression in the sexually dimorphic BNST of male but not
      female GAD67 mice and TMT predator odor stress effects upon spatial memory
      retrieval.
AB  - The bed nucleus of the stria terminalis (BNST) is an important region for 2,5
      dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in
      mice. It is sexually dimorphic and a region for corticotropin-releasing factor
      (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala
      to the BNST gives point to relevant interactions between CRF and GABA activity in
      these brain regions. Hence, to investigate sexual dimorphism of stress-induced
      neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression
      in stress-related brain regions in male and female GAD67 mice and their wild-type
      littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons
      caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show
      higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT
      and control odor exposure. While CRF neurons in the BNST are predominantly
      GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the
      deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF
      increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons
      in females could explain the differences in CRF mRNA levels between male and
      female GAD67 mice. Effects of odor exposure were studied in a radial arm maze
      (RAM) task. Results show impaired retrieval of spatial memory after acute TMT
      exposure in both sexes and genotypes. However, only GAD67 mice show increased
      working memory errors after control odor exposure. Our work elicits GAD67 mice as
      a model to further study interactions of GABA and CRF in the BNST for a better
      understanding of how sex-specific characteristics of the brain may contribute to
      differences in anxiety- and stress-related psychological disorders. 

PMID- 24946071
TI  - Fear extinction learning can be impaired or enhanced by modulation of the CRF
      system in the basolateral nucleus of the amygdala.
AB  - The neuropeptide corticotropin-releasing factor (CRF) is released during periods
      of anxiety and modulates learning and memory formation. One region with
      particularly dense concentrations of CRF receptors is the basolateral nucleus of
      the amygdala (BLA), a critical structure for both Pavlovian fear conditioning and
      fear extinction. While CRF has the potential to modify amygdala-dependent
      learning, its effect on fear extinction has not yet been assessed. In the present
      study, we examined the modulatory role of CRF on within-session extinction and
      fear extinction consolidation. Intra-BLA infusions of the CRF binding protein
      ligand inhibitor CRF(6-33) which increases endogenous levels of free CRF, or
      intra-BLA infusions of exogenous CRF made prior to fear extinction learning did
      not affect either fear expression or within-session extinction learning. However,
      when these animals were tested twenty-four hours later, drug free, they showed
      impairments in extinction memory. Conversely, intra-BLA infusions of the CRF
      receptor antagonist alpha-helical CRF(9-41) enhanced memory of fear extinction.
      These results suggest that increased CRF levels within the BLA at the time of
      fear extinction learning actively impair the consolidation of long-term fear
      extinction. 

PMID- 24946073
TI  - APOE and BDNF Val66Met polymorphisms combine to influence episodic memory
      function in older adults.
AB  - Genetic polymorphisms of apolipoprotein E (APOE) and brain-derived neurotrophic
      factor (BDNF) have shown inconsistent associations with healthy adult cognitive
      functions. Recent investigations have suggested that APOE polymorphisms do not
      contribute to non-pathological cognitive function and that any effect is likely
      due to prodromal Alzheimer's disease (AD). Similarly, although BDNF Val66Met
      polymorphisms affect hippocampal morphology and function, associations with
      learning and/or memory have not always been found. This study sought to determine
      whether APOE and BDNF polymorphisms were associated, either independently or in
      combination, with adult cognition. Comprehensive neuropsychological assessments
      were conducted on 433 older adults, aged 50-79 years (M=62.16, SD=6.81), which
      yielded measures of episodic memory, working memory, executive function, and
      language processing. Participants underwent comprehensive neuropsychological
      assessment to ensure that only cognitively intact individuals comprised the
      sample. APOE and BDNF polymorphic data were used as predictors in general linear
      models that assessed composite cognitive domain variables, while covarying for
      education and age. Although no main effects for APOE or BDNF were found, the
      analysis identified a significant APOE*BDNF interaction that predicted episodic
      memory performance (p=.02, eta(2)=.02). Post-hoc analyses demonstrated that in
      BDNF Val homozygotes, the cognitive consequences of APOE polymorphisms were
      minimal. However, in BDNF Met carriers, the hypothesized beneficial/detrimental
      effects of APOE polymorphisms were found. Our data show that concurrent
      consideration of both APOE and BDNF polymorphisms are required in order to
      witness a cognitive effect in healthy older adults. 

PMID- 24946074
TI  - REM sleep diversity following the pedunculopontine tegmental nucleus lesion in
      rat.
AB  - The aim of this study was to demonstrate that two REM clusters, which emerge
      following bilateral pedunculopontine tegmental nucleus (PPT) lesions in rats, are
      two functionally distinct REM states. We performed the experiments in Wistar
      rats, chronically instrumented for sleep recording. Bilateral PPT lesions were
      produced by the microinfusion of 100 nl of 0.1M ibotenic acid (IBO). Following a
      recovery period of 2 weeks, we recorded their sleep for 6h. Bilateral PPT lesions
      were identified by NADPH - diaphorase histochemistry. We applied Fourier analysis
      to the signals acquired throughout the 6h recordings, and each 10s epoch was
      differentiated as a Wake, NREM or REM state. We analyzed the topography of the
      sleep/wake states architecture and their transition structure, their all state
      related EEG microstructures, and the sensorimotor (SMCx) and motor (MCx) cortex
      REM related cortico-muscular coherences (CMCs). Bilateral PPT lesion in rats
      increased the likelihood of the emergence of two distinct REM sleep states,
      specifically expressed within the MCx: REM1 and REM2. Bilateral PPT lesion did
      not change the sleep/wake states architecture of the SMCx, but pathologically
      increased the duration of REM1 within the MCx, alongside increasing
      Wake/REM1/Wake and NREM/REM2/NREM transitions within both cortices. In addition,
      the augmented total REM SMCx EEG beta amplitude and REM1 MCx EEG theta amplitude
      was the underlying EEG microstructure pathology. PPT lesion induced REM1 and REM2
      are differential states with regard to total EMG power, topographically distinct
      EEG microstructures, and locomotor drives to nuchal musculature.

PMID- 24946076
TI  - PDGF, pericytes and the pathogenesis of idiopathic basal ganglia calcification
      (IBGC).
AB  - Platelet-derived growth factors (PDGFs) are important mitogens for various types
      of mesenchymal cells, and as such, they exert critical functions during
      organogenesis in mammalian embryonic and early postnatal development. Increased
      or ectopic PDGF activity may also cause or contribute to diseases such as cancer
      and tissue fibrosis. Until recently, no loss-of-function (LOF) mutations in PDGF
      or PDGF receptor genes were reported as causally linked to a human disease. This
      changed in 2013 when reports appeared on presumed LOF mutations in the genes
      encoding PDGF-B and its receptor PDGF receptor-beta (PDGF-Rbeta) in familial
      idiopathic basal ganglia calcification (IBGC), a brain disease characterized by
      anatomically localized calcifications in or near the blood microvessels. Here, we
      review PDGF-B and PDGF-Rbeta biology with special reference to their functions in
      brain-blood vessel development, pericyte recruitment and the regulation of the
      blood-brain barrier. We also discuss various scenarios for IBGC pathogenesis
      suggested by observations in patients and genetically engineered animal models of
      the disease. 

PMID- 24946077
TI  - Failure of perivascular drainage of beta-amyloid in cerebral amyloid angiopathy.
AB  - In Alzheimer's disease, amyloid-beta (Abeta) accumulates as insoluble plaques in
      the brain and deposits in blood vessel walls as cerebral amyloid angiopathy
      (CAA). The severity of CAA correlates with the degree of cognitive decline in
      dementia. The distribution of Abeta in the walls of capillaries and arteries in
      CAA suggests that Abeta is deposited in the perivascular pathways by which
      interstitial fluid drains from the brain. Soluble Abeta from the extracellular
      spaces of gray matter enters the basement membranes of capillaries and drains
      along the arterial basement membranes that surround smooth muscle cells toward
      the leptomeningeal arteries. The motive force for perivascular drainage is
      derived from arterial pulsations combined with the valve effect of proteins
      present in the arterial basement membranes. Physical and biochemical changes
      associated with arteriosclerosis, aging and possession of apolipoprotein E4
      genotype lead to a failure of perivascular drainage of soluble proteins,
      including Abeta. Perivascular cells associated with arteries and the lymphocytes
      recruited in the perivenous spaces contribute to the clearance of Abeta. The
      failure of perivascular clearance of Abeta may be a major factor in the
      accumulation of Abeta in CAA and may have significant implications for the design
      of therapeutics for the treatment of Alzheimer's disease. 

PMID- 24946078
TI  - The fibrotic scar in neurological disorders.
AB  - Tissue fibrosis, or scar formation, is a common response to damage in most organs
      of the body. The central nervous system (CNS) is special in that fibrogenic cells
      are restricted to vascular and meningeal niches. However, disruption of the blood
      brain barrier and inflammation can unleash stromal cells and trigger scar
      formation. Astroglia segregate from the inflammatory lesion core, and the so
      called "glial scar" composed of hypertrophic astrocytes seals off the intact
      neural tissue from damage. In the lesion core, a second type of "fibrotic scar"
      develops, which is sensitive to inflammatory mediators. Genetic fate mapping
      studies suggest that pericytes and perivascular fibroblasts are activated, but
      other precursor cells may also be involved in generating a transient fibrous
      extracellular matrix in the CNS. The stromal cells sense inflammation and attract
      immune cells, which in turn drive myofibroblast transdifferentiation. We believe
      that the fibrotic scar represents a major barrier to CNS regeneration. Targeting
      of fibrosis may therefore prove to be a valuable therapeutic strategy for
      neurological disorders such as stroke, spinal cord injury and multiple sclerosis.

PMID- 24946081
TI  - Teratoid Wilms' tumor exhibiting extensive squamous differentiation.
AB  - Teratoid Wilms' tumor is a rare renal tumor. Herein, we report an unusual variant
      of such tumor which simulated renal teratoma because of abundant keratinized
      squamous epithelium within the tumor. 

PMID- 24946082
TI  - Efficacy of growth factor in promoting early osseointegration.
AB  - A preclinical study was conducted to evaluate the feasibility of 2 different
      topical formulations of recombinant human platelet-derived growth factor-BB
      (rhPDGF-BB) to promote early osseointegration and enhanced bone-to-implant
      contact (BIC) for dental implants placed in an edentulous ridge. Six female
      beagle dogs were divided into 3 groups. The control group included 4 implants
      with no coating; test group A included 10 implants with commercially available
      rhPDGF-BB formulation coating; and second test group B included 10 implants with
      prototype viscous rhPDGF-BB coating. Three dogs were sacrificed at 3 weeks (12
      implants) and the remaining 3 dogs at 6 weeks after implant placement (12
      implants). The specimens were retrieved for histological evaluation, and revealed
      an uneventful healing of all implants without any sign of an inflammatory
      response at the different time intervals. Furthermore, the bone was in very close
      contact with the implants' surfaces with no evidence of intervening fibrous
      tissue layers. At 3 weeks, new bone formation between most implant threads on
      rhPDGF-BB coated implants was evident, whereas in the control group only a thin
      and sparse amount of new bone was noted. At 6 weeks, the commercially available
      rhPDGF-BB formulation coated implant group (Group A) showed more trabecular bone
      and higher BIC compared to the other 2 groups. Histologically, the results in
      this study showed that use of conventionally available rhPDGF-BB formulation as
      the implant surface treatment may accelerate the process of osseointegration and
      enhance BIC. 

PMID- 24946083
TI  - Vestibular deficits leading to disequilibrium and falls in ambulatory amyotrophic
      lateral sclerosis.
AB  - OBJECTIVE: To assess vestibular deficits in response to disequilibrium in
      ambulatory individuals with amyotrophic lateral sclerosis (ambALS). DESIGN: All
      participants completed standard protocols for the Sensory Organization Test (SOT)
      by computerized dynamic posturography. SETTING: Multidisciplinary amyotrophic
      lateral sclerosis clinic at an academic medical center. PARTICIPANTS: Study
      participants (N=34) consisted of ambALS (n=19) and healthy controls (HC) (n=15).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Equilibrium scores (ESs)
      obtained from averaged sway amplitude in condition 5 (ES5) and condition 6 (ES6)
      of the SOT. RESULTS: In conditions of altered somatosensory information with
      vision absent or vision sway-referenced, the mean +/- SD scores for ambALS
      (ES5=51.4+/-22.5; ES6=50.8+/-22.1) were lower than those for HC (ES5=65.4+/-11.7,
      P<=.03; ES6=58.9+/-12.5, P>.05). Seven ambALS (37%) experienced a total of 19
      falls during the sway-referenced support test conditions. There were no falls in
      the HC. CONCLUSIONS: Nearly 37% of ambALS with normal clinical balance testing
      have decreased ability to use the vestibular input and required increased
      reliance on visual input for postural orientation to sustain equilibrium. The
      mechanism of this alteration in sensory preference is not completely clear.
      Extrapyramidal involvement early in ALS may be indicated.

PMID- 24946075
TI  - The pericyte: a forgotten cell type with important implications for Alzheimer's
      disease?
AB  - Pericytes are cells in the blood-brain barrier (BBB) that degenerate in
      Alzheimer's disease (AD), a neurodegenerative disorder characterized by early
      neurovascular dysfunction, elevation of amyloid beta-peptide (Abeta), tau
      pathology and neuronal loss, leading to progressive cognitive decline and
      dementia. Pericytes are uniquely positioned within the neurovascular unit between
      endothelial cells of brain capillaries, astrocytes and neurons. Recent studies
      have shown that pericytes regulate key neurovascular functions including BBB
      formation and maintenance, vascular stability and angioarchitecture, regulation
      of capillary blood flow, and clearance of toxic cellular by-products necessary
      for normal functioning of the central nervous system (CNS). Here, we review the
      concept of the neurovascular unit and neurovascular functions of CNS pericytes.
      Next, we discuss vascular contributions to AD and review new roles of pericytes
      in the pathogenesis of AD such as vascular-mediated Abeta-independent
      neurodegeneration, regulation of Abeta clearance and contributions to tau
      pathology, neuronal loss and cognitive decline. We conclude that future studies
      should focus on molecular mechanisms and pathways underlying aberrant signal
      transduction between pericytes and its neighboring cells within the neurovascular
      unit, that is, endothelial cells, astrocytes and neurons, which could represent
      potential therapeutic targets to control pericyte degeneration in AD and the
      resulting secondary vascular and neuronal degeneration. 

PMID- 24946085
TI  - Loading and protection of hydrophilic molecules into liposome-templated
      polyelectrolyte nanocapsules.
AB  - Compartmentalized systems produced via the layer-by-layer (LbL) self-assembly
      method have been produced by alternatively depositing alginate and chitosan
      layers onto cores of liposomes. The combination of dynamic light scattering
      (DLS), zeta potential, and transmission electron microscopy (TEM) techniques
      provides detailed information on the stability, dimensions, charge, and wall
      thickness of these polyelectrolyte globules. TEM microphotographs demonstrate the
      presence of nanocapsules with an average diameter of below 300 nm and with a
      polyelectrolyte wall thickness of about 20 nm. The possibility of encapsulating
      and releasing molecules from this type of nanocapsule was demonstrated by loading
      FITC-dextrans of different molecular weights in the liposome system. The release
      of the loaded molecules from the nanocapsule was demonstrated after liposome core
      dissolution. Even at low molecular weight (20 kDa), the nanocapsules appear to be
      appropriate for prolonged molecule compartmentalization and protection. By means
      of the Ritger-Peppas model, non-Fickian transport behavior was detected for the
      diffusion of dextran through the polyelectrolyte wall. Values of the diffusion
      coefficient were calculated and yield useful information regarding
      chitosan/alginate hollow nanocapsules as drug-delivery systems. The influence of
      the pH on the release properties was also considered. The results indicate that
      vesicle-templated hollow polyelectrolyte nanocapsules show great potential as
      novel controllable drug-delivery devices for biomedical and biotechnological
      applications. 

PMID- 24946084
TI  - Investigating measures of intensity during a structured upper limb exercise
      program in stroke rehabilitation: an exploratory study.
AB  - OBJECTIVES: To use 3 measures of intensity-time, observed repetitions, and wrist
      accelerometer activity counts-to describe the intensity of exercise carried out
      when completing a structured upper limb exercise program, and to explore whether
      a relationship exists between wrist accelerometer activity counts and observed
      repetitions. DESIGN: Observational study design. SETTING: Rehabilitation center
      research laboratory. PARTICIPANTS: Community-dwelling stroke survivors (N=13)
      with upper limb hemiparesis. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES:
      Time engaged in exercise, total repetitions, and accelerometer activity counts
      for the affected upper limb. RESULTS: Mean session time +/- SD was 48.5+/-7.8
      minutes. Participants were observed to be engaged in exercises for 63.8%+/-7.5%
      of the total session time. The median number of observed repetitions per session
      was 340 (interquartile range [IQR], 199-407), of which 251 (IQR, 80-309) were
      purposeful repetitions. Wrist accelerometers showed the stroke survivors' upper
      limbs to be moving for 75.7%+/-15.9% of the total session time. Purposeful
      repetitions and activity counts were found to be significantly correlated
      (rho=.627, P<.05). CONCLUSIONS: Stroke survivors were not actively engaged in
      exercises for approximately one third of each exercise session. Overall session
      time may not be the most accurate measure of intensity. Counting repetitions was
      feasible when using a structured exercise program and provides a clinically
      meaningful way of monitoring intensity and progression. Wrist accelerometers
      provided an objective measure for how much the arm moves, which correlated with
      purposeful repetitions. Further research using repetitions and accelerometers as
      measures of intensity is warranted.

PMID- 24946086
TI  - Bioconjugates of rhizavidin with single domain antibodies as bifunctional
      immunoreagents.
AB  - Use of the avidin-biotin binding interaction for immunoassay applications is
      widespread. One advantageous immunoreagent is the recombinant fusion of an
      antibody fragment with a biotin binding protein. These genetic fusions alleviate
      the need to prepare chemical conjugates to achieve molecules that combine target
      recognition with signal transduction or to facilitate the directional
      immobilization of the binding element. In order for such a fusion protein to be
      useful, however, it must be able to be produced in good yield. Unfortunately,
      recombinant production of avidin or streptavidin as well as bioconjugates derived
      thereof has been problematic. An alternative biotin binding molecule called
      rhizavidin has been described, which forms a homodimer instead of a tetramer, but
      it has not been evaluated in genetic fusions with antibody binding domains.
      Single domain antibodies, the variable domain derived from camelid heavy chain
      only antibodies, offer binding domains with high affinity, and solubility that
      are well expressed in Escherichia coli. In this work, we prepared an anti-ricin
      single domain antibody - rhizavidin bioconjugate and evaluated it on the basis of
      its production in E. coli and on its activity in comparison to a streptavidin
      core bioconjugate and unfused single domain antibody. The single domain antibody
      rhizavidin bioconjugate produced much better than its streptavidin core
      counterparts, yielding an average of 14 mg/L, a 20-fold improvement. When used in
      assays the rhizavidin conjugate provided the same desirable characteristics as
      the streptavidin core fusion as both capture and detection reagents. Since
      rhizavidin and single domain antibodies both display impressive thermal
      stabilities their fusion provides a route to achieve robust bifunctional
      immunoreagents.

PMID- 24946087
TI  - The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin
      emanations, urine, feces and saliva.
AB  - Breath analysis is a young field of research with its roots in antiquity. Antoine
      Lavoisier discovered carbon dioxide in exhaled breath during the period 1777
      1783, Wilhelm (Vilem) Petters discovered acetone in breath in 1857 and Johannes
      Muller reported the first quantitative measurements of acetone in 1898. A recent
      review reported 1765 volatile compounds appearing in exhaled breath, skin
      emanations, urine, saliva, human breast milk, blood and feces. For a large number
      of compounds, real-time analysis of exhaled breath or skin emanations has been
      performed, e.g., during exertion of effort on a stationary bicycle or during
      sleep. Volatile compounds in exhaled breath, which record historical exposure,
      are called the 'exposome'. Changes in biogenic volatile organic compound
      concentrations can be used to mirror metabolic or (patho)physiological processes
      in the whole body or blood concentrations of drugs (e.g. propofol) in clinical
      settings-even during artificial ventilation or during surgery. Also compounds
      released by bacterial strains like Pseudomonas aeruginosa or Streptococcus
      pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for
      example, was observed in the headspace of Streptococcus pneumonia in
      concentrations up to 1420 ppb. Fecal volatiles have been implicated in
      differentiating certain infectious bowel diseases such as Clostridium difficile,
      Campylobacter, Salmonella and Cholera. They have also been used to differentiate
      other non-infectious conditions such as irritable bowel syndrome and inflammatory
      bowel disease. In addition, alterations in urine volatiles have been used to
      detect urinary tract infections, bladder, prostate and other cancers.
      Peroxidation of lipids and other biomolecules by reactive oxygen species produce
      volatile compounds like ethane and 1-pentane. Noninvasive detection and
      therapeutic monitoring of oxidative stress would be highly desirable in
      autoimmunological, neurological, inflammatory diseases and cancer, but also
      during surgery and in intensive care units. The investigation of cell cultures
      opens up new possibilities for elucidation of the biochemical background of
      volatile compounds. In future studies, combined investigations of a particular
      compound with regard to human matrices such as breath, urine, saliva and cell
      culture investigations will lead to novel scientific progress in the field. 

PMID- 24946088
TI  - The IL-6-STAT3 axis mediates a reciprocal crosstalk between cancer-derived
      mesenchymal stem cells and neutrophils to synergistically prompt gastric cancer
      progression.
AB  - Emerging evidence indicate that mesenchymal stem cells (MSCs) affect tumor
      progression by reshaping the tumor microenvironment. Neutrophils are essential
      component of the tumor microenvironment and are critically involved in cancer
      progression. Whether the phenotype and function of neutrophils is influenced by
      MSCs is not well understood. Herein, we investigated the interaction between
      neutrophils and gastric cancer-derived MSCs (GC-MSCs) and explored the biological
      role of this interaction. We found that GC-MSCs induced the chemotaxis of
      neutrophils and protected them from spontaneous apoptosis. Neutrophils were
      activated by the conditioned medium from GC-MSCs with increased expression of IL
      8, TNFalpha, CCL2, and oncostatin M (OSM). GC-MSCs-primed neutrophils augmented
      the migration of gastric cancer cells in a cell contact-dependent manner but had
      minimal effect on gastric cancer cell proliferation. In addition, GC-MSCs-primed
      neutrophils prompted endothelial cells to form tube-like structure in vitro. We
      demonstrated that GC-MSCs stimulated the activation of STAT3 and ERK1/2 pathways
      in neutrophils, which was essential for the functions of activated neutrophils.
      We further revealed that GC-MSCs-derived IL-6 was responsible for the protection
      and activation of neutrophils. In turn, GC-MSCs-primed neutrophils induced the
      differentiation of normal MSCs into cancer-associated fibroblasts (CAFs).
      Collectively, our results suggest that GC-MSCs regulate the chemotaxis, survival,
      activation, and function of neutrophils in gastric cancer via an IL-6-STAT3
      ERK1/2 signaling cascade. The reciprocal interaction between GC-MSCs and
      neutrophils presents a novel mechanism for the role of MSCs in remodeling cancer
      niche and provides a potential target for gastric cancer therapy. 

PMID- 24946089
TI  - Tissue-specific deregulation of selected HDACs characterizes ALS progression in
      mouse models: pharmacological characterization of SIRT1 and SIRT2 pathways.
AB  - Acetylation homeostasis is thought to play a role in amyotrophic lateral
      sclerosis, and treatment with inhibitors of histone deacetylases has been
      considered a potential and attractive therapeutic approach, despite the lack of a
      thorough study of this class of proteins. In this study, we have considerably
      extended previous knowledge on the expression of 13 histone deacetylases in
      tissues (spinal cord and muscle) from mice carrying two different ALS-linked SOD1
      mutations (G93A-SOD1 and G86R-SOD1). We have then focused on class III histone
      deacetylases SIRT1 and SIRT2 that are considered relevant in neurodegenerative
      diseases. SIRT1 decreases in the spinal cord, but increases in muscle during the
      progression of the disease, and a similar expression pattern is observed in the
      corresponding cell models (neuroblastoma and myoblasts). SIRT2 mRNA expression
      increases in the spinal cord in both G93A-SOD1 and G86R-SOD1 mice but protein
      expression is substantially unchanged in all the models examined. At variance
      with other sirtuin modulators (sirtinol, AGK2 and SRT1720), the well-known SIRT1
      inhibitor Ex527 has positive effects on survival of neuronal cells expressing
      mutant SOD1, but this effect is neither mediated by SIRT1 inhibition nor by SIRT2
      inhibition. These data call for caution in proposing sirtuin modulation as a
      target for treatment. 

PMID- 24946090
TI  - Concentration-dependent wrestling between detrimental and protective effects of
      H2O2 during myocardial ischemia/reperfusion.
AB  - Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress are
      paradoxically implicated in myocardial ischemia/reperfusion (I/R) injury and
      cardioprotection. However, the precise interpretation for the dual roles of ROS
      and its relationship with the ER stress during I/R remain elusive. Here we
      investigated the concentration-dependent effects of hydrogen peroxide (H2O2)
      preconditioning (PC) and postconditioning (PoC) on the ER stress and prosurvival
      reperfusion injury salvage kinase (RISK) activation using an ex vivo rat
      myocardial I/R model. The effects of H2O2 PC and PoC showed three phases. At a
      low level (1 MUM), H2O2 exacerbated I/R-induced left ventricular (LV) contractile
      dysfunction and ER stress, as indicated by enhanced phosphorylation of protein
      kinase-like ER kinase and expressions of glucose-regulated protein 78, X-box
      binding protein 1 splicing variant, TNF receptor-associated factor 2, activating
      transcription factor-6 cleaved 50 kDa fragment, and caspase-12 cleavage, but the
      I/R-induced RISK activation including protein kinase B (PKB/Akt) and protein
      kinase CE (PKCE) remained unchanged. Consistently, the postischemic LV
      performance in 1 MUM H2O2 PC and PoC groups was improved by inhibiting ER stress
      with 4-phenyl butyric acid but not affected by the ER stress inducer,
      tunicamycin. At a moderate level (10-100 MUM), H2O2 significantly improved
      postischemic LV performance and enhanced RISK activation, but it did no further
      alter the ER stress. The cardioprotection but not ER stress was abrogated with
      Akt or PKCE inhibitor wortmannin or EV1-2. At a high level (1 mM), H2O2 markedly
      aggravated the reperfusion injury and the oxidative stress but did not further
      enhance the RISK activation. In addition, 1 or 20 MUM of H2O2 PC did not alter
      cardioprotective effects of ischemic PC in postischemic contractile performance
      and protein oxidation. Our data suggest that the differential effects of H2O2 are
      derived from a concentration-dependent wrestling between its detrimental stress
      and protective signaling.

PMID- 24946092
TI  - Recent advances in tin dioxide materials: some developments in thin films,
      nanowires, and nanorods.

PMID- 24946091
TI  - Comparative analysis of the secretion capability of early and late flagellar type
      III secretion substrates.
AB  - A remarkable feature of the flagellar-specific type III secretion system (T3SS)
      is the selective recognition of a few substrate proteins among the many thousand
      cytoplasmic proteins. Secretion substrates are divided into two specificity
      classes: early substrates secreted for hook-basal body (HBB) construction and
      late substrates secreted after HBB completion. Secretion was reported to require
      a disordered N-terminal secretion signal, mRNA secretion signals within the 5'
      untranslated region (5'-UTR) and for late substrates, piloting proteins known as
      the T3S chaperones. Here, we utilized translational beta-lactamase fusions to
      probe the secretion efficacy of the N-terminal secretion signal of fourteen
      secreted flagellar substrates in Salmonella enterica. We observed a surprising
      variety in secretion capability between flagellar proteins of the same secretory
      class. The peptide secretion signals of the early-type substrates FlgD, FlgF,
      FlgE and the late-type substrate FlgL were analysed in detail. Analysing the role
      of the 5'-UTR in secretion of flgB and flgE revealed that the native 5'-UTR
      substantially enhanced protein translation and secretion. Based on our data, we
      propose a multicomponent signal that drives secretion via the flagellar T3SS.
      Both mRNA and peptide signals are recognized by the export apparatus and together
      with substrate-specific chaperones allowing for targeted secretion of flagellar
      substrates. 

PMID- 24946093
TI  - Radiosynthesis of 3-indolyl[1-11C]acetic acid for phyto-PET-imaging: an improved
      production procedure and formulation method.
AB  - An improved production procedure and formulation method for the carbon-11
      radiolabeled phytohormone, 3-indolyl-[l-(11)C]acetic acid ([(11)C]IAA), was
      developed by modifying selected original reaction parameters. This updated
      procedure both doubled the yield (from 25.9+/-6.7% (n=12) to 61.0+/-0.3% (n=10))
      and increased the concentration (0.2-0.4 GBq/0.15-0.3 mL), enabling us to provide
      the radiotracer [(11)C]IAA suitable for in vivo phyto-PET-imaging studies. The
      specific activity was improved by more than a factor of three (26.7+/-5.6
      GBq/umol to 82.5+/-36.1 GBq/umol). The total synthesis time for both production
      and formulation was 81.8+/-3.0 min (n=10). In addition, a streamlined semi-remote
      controlled production system, containing five processing modules, was designed
      and built for routine [(11)C]IAA production. This integrated system facilitated
      routine high radiation level production of [(11)C]IAA while minimizing radiation
      exposure to the production chemists.

PMID- 24946095
TI  - Spontaneous vesicle phase formation by pseudogemini surfactants in aqueous
      solutions.
AB  - The phase behavior of a kind of pseudogemini surfactant in aqueous solutions,
      formed by the mixture of sodium dodecyl benzene sulfonate (SDBS) and butane-1,4
      bis (methylimidazolium bromide) ([mim-C4-mim]Br2) or butane-1,4
      bis(methylpyrrolidinium bromide) ([mpy-C4-mpy]Br2) in a molar ratio of 2 : 1, is
      reported in the present work. When [mim-C4-mim]Br2 or [mpy-C4-mpy]Br2 is mixed
      with SDBS in aqueous solutions, one cationic [mim-C4-mim]Br2 or [mpy-C4-mpy]Br2
      molecule "bridges" two SDBS molecules by noncovalent interactions (e.g.
      electrostatic, pi-pi stacking, and sigma-pi interactions), behaving like a
      pseudogemini surfactant. Vesicles can be formed by this kind of pseudogemini
      surfactant, determined by freeze-fracture transmission electron microscopy (FF
      TEM) or cryogenic-transmission electron microscopy (cryo-TEM) and dynamic light
      scattering (DLS). The mixed system of sodium dodecyl sulfate (SDS) with [mim-C4
      mim]Br2 or [mpy-C4-mpy]Br2 was also constructed, and only micelles were observed.
      We infer that a pseudogemini surfactant is formed under the synergic effect of
      electrostatic, pi-pi stacking, and sigma-pi interactions in the SDBS/[mim-C4
      mim]Br2/H2O system, while electrostatic attraction and hydrophobic interactions
      may provide the directional force for vesicle formation in the SDBS/[mpy-C4
      mpy]Br2/H2O system. 

PMID- 24946096
TI  - Class I-specific histone deacetylase inhibitor MS-275 overrides TRAIL-resistance
      in melanoma cells by downregulating c-FLIP.
AB  - Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) has selective
      killing effect toward malignant cells; however some human melanomas are
      intrinsically resistant. In this study, we have shown that class I-specific
      histone deacetylase inhibitor (HDACi) MS-275 can synergize with TRAIL to induce
      apoptosis in TRAIL-resistant cell lines and to enhance susceptibility of
      sensitive cells. Conversely, class II-selective HDACi MC1575 has shown no effect
      on the resistance of melanoma cells and was able exclusively to increase TRAIL
      induced cell death in responsive cells. Both the HDACis variably increased DR4,
      DR5, and procaspase 8 expression, regardless whether cells were TRAIL-sensitive
      or TRAIL-resistant. However, only MS-275 markedly decreased the expression levels
      of both the long and short c-FLIP isoforms. RNAi-mediated c-FLIP silencing
      resulted in caspase 8-dependent apoptosis in survivor cells which was comparable
      to that observed following MS-275 treatment. Accordingly, enforced expression of
      ectopic c-FLIP has abolished the cooperative induction of apoptosis by the
      combination of MS-275 and TRAIL. These data indicate that c-FLIP is a critical
      regulator of death ligand sensitivity in melanoma. Inhibition of class I HDAC
      isoenzymes 1, 2 and 3 has resulted to be functionally important for c-FLIP
      downregulation by MS-275. In contrast, knockdown of class II HDACs has had no
      effect on c-FLIP expression, thus explaining the dual incapacity of MC1575 to
      inhibit c-FLIP expression and sensitize cells resistant to TRAIL. The data
      reported here suggest that MS-275 represents a promising therapeutic approach in
      combination with TRAIL for treatment of cutaneous and uveal melanoma due to its
      ability to reduce c-FLIP expression. 

PMID- 24946097
TI  - Verification of a Parkinson's disease protein signature in T-lymphocytes by
      multiple reaction monitoring.
AB  - Diagnosis of Parkinson's disease, the second most common neurodegenerative
      disease, is based on the appearance of motor symptoms. A panel of protein
      biomarkers in the T-lymphocyte proteome was previously proposed as a Parkinson's
      disease signature. Here, we designed an LC-MS based method to quantitatively
      evaluate this protein signature by multiple reaction monitoring (MRM) in T
      lymphocytes and peripheral blood mononuclear cells from a new cohort of nine
      patients with Parkinson's disease and nine unaffected subjects. Patients were
      classified using the discriminant function obtained from two-dimensional
      electrophoresis and protein amounts measured by MRM, thus assigning seven
      controls out of nine as true negatives and nine patients out of nine as true
      positives. A good discriminant power was obtained by selecting a subset of
      peptides from the protein signature, with an area under the receiver operating
      characteristic curve of 0.877. A similar result is achieved by evaluating all
      peptides of a selected panel of proteins (gelsolin, moesin, septin-6, twinfilin
      2, lymphocyte-specific protein 1, vimentin, transaldolase), with an area under
      the curve of 0.840. Conversely, the signature was not able to classify the
      enrolled subjects when evaluated in whole mononuclear cells. Overall, this report
      shows the portability of the proposed method to a large-scale clinical validation
      study. 

PMID- 24946099
TI  - Load capacity improvements in nucleic acid based systems using partially open
      feedback control.
AB  - Synthetic biology is facilitating novel methods and components to build in vivo
      and in vitro circuits to better understand and re-engineer biological networks.
      Recently, Kim and Winfree have synthesized a remarkably elegant network of
      transcriptional oscillators in vitro using a modular architecture of synthetic
      gene analogues and a few enzymes that, in turn, could be used to drive a variety
      of downstream circuits and nanodevices. However, these oscillators are sensitive
      to initial conditions and downstream load processes. Furthermore, the
      oscillations are not sustained since the inherently closed design suffers from
      enzyme deactivation, NTP fuel exhaustion, and waste product build up. In this
      paper, we show that a partially open architecture in which an [Symbol: see text]1
      adaptive controller, implemented inside an in silico computer that resides
      outside the wet-lab apparatus, can ensure sustained tunable oscillations in two
      specific designs of the Kim-Winfree oscillator networks. We consider two broad
      cases of operation: (1) the oscillator network operating in isolation and (2) the
      oscillator network driving a DNA tweezer subject to a variable load. In both
      scenarios, our simulation results show a significant improvement in the
      tunability and robustness of these oscillator networks. Our approach can be
      easily adopted to improve the loading capacity of a wide range of synthetic
      biological devices.

PMID- 24946098
TI  - FOXO1-dependent up-regulation of MAP kinase phosphatase 3 (MKP-3) mediates
      glucocorticoid-induced hepatic lipid accumulation in mice.
AB  - Long-term treatment with glucocorticoids (GCs) or dysregulation of endogenous GC
      levels induces a series of metabolic diseases, such as insulin resistance,
      obesity and type 2 diabetes. We previously showed that MAP kinase phosphatase-3
      (MKP-3) plays an important role in glucose metabolism. The aim of this study is
      to investigate the role of MKP-3 in GC-induced metabolic disorders. Dexamethasone
      (Dex), a synthetic GC, increases MKP-3 protein expression both in cultured
      hepatoma cells and in the liver of lean mice. This effect is likely mediated by
      forkhead box protein O1 (FOXO1) because disruption of endogenous FOXO1 function
      by either interfering RNA mediated FOXO1 knockdown or overexpression of a
      dominant negative FOXO1 mutant blocks Dex-induced upregulation of MKP-3 protein.
      In addition, overexpression of FOXO1 is sufficient to induce MKP-3 protein
      expression. MKP-3 deficient mice are protected from several side effects of
      chronic Dex exposure, such as body weight gain, adipose tissue enlargement,
      hepatic lipid accumulation, and insulin resistance. The beneficial phenotypes in
      mice lacking MKP-3 are largely attributed to the absence of MKP-3 in the liver
      since only hepatic insulin signaling has been preserved among the three insulin
      target tissues (liver, muscle and adipose tissue).

PMID- 24946100
TI  - Vitamin D deficiency in neovascular versus nonneovascular age-related macular
      degeneration.
AB  - PURPOSE: To compare 25-hydroxyvitamin D (25OHD) levels in patients with
      neovascular age-related macular degeneration (NVAMD) with patients with
      nonneovascular age-related macular degeneration and control patients. METHODS:
      Medical records of all patients diagnosed with age-related macular degeneration
      and tested for serum 25OHD level at a single medical center were reviewed.
      Control patients were selected from patients diagnosed with pseudophakia but
      without age-related macular degeneration. The lowest 25OHD level available for
      each patient was recorded. RESULTS: Two hundred sixteen patients with
      nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non-age
      related macular degeneration control patients were included. The levels of 25OHD
      (mean +/- SD) were significantly lower in NVAMD patients (26.1 +/- 14.4 ng/mL)
      versus nonneovascular age-related macular degeneration (31.5 +/- 18.2 ng/mL, P =
      0.003) and control (29.4 +/- 10.1 ng/mL, P = 0.049) patients. The prevalence of
      vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe
      deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of
      25OHD was associated with a 0.35 (95% confidence interval, 0.18-0.68) odds ratio
      for NVAMD. CONCLUSION: This is the largest study to compare 25OHD levels in
      patients with the different clinical forms of age-related macular degeneration.
      Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD
      patients. These associations suggest that further research is necessary regarding
      vitamin D deficiency as a potentially modifiable risk factor for the development
      of NVAMD.

PMID- 24946101
TI  - Long-term functional and morphologic retinal changes after ranibizumab and
      photodynamic therapy in myopic choroidal neovascularization.
AB  - PURPOSE: To assess and compare the long-term functional and anatomical outcomes
      in eyes with myopic choroidal neovascularization (CNV) treated with intravitreal
      injections of ranibizumab or with photodynamic therapy (PDT). METHODS: Eighty
      five eyes of 85 consecutive patients with myopic CNV and treated with either PDT
      (43/85) or ranibizumab 0.5 mg (42/85) and at least 24 months of follow-up were
      collected. Data from the best-corrected visual acuity, optical coherence
      tomography, and fluorescein angiography were compared between the groups.
      Differences in the regression pattern of myopic CNV and the rate of chorioretinal
      atrophy development were also compared between the groups. RESULTS: The effect of
      treatment over time on best-corrected visual acuity and the central retinal
      thickness was significantly greater in the ranibizumab group (P = 0.0012 and P <
      0.0002, respectively), with eyes treated with ranibizumab showing a significant
      central retinal thickness decrease since the first visit and maintained until 24
      months. The proportion of patients showing a complete closure of CNV was similar
      between the groups (93% [39 of 42 eyes in the ranibizumab group] vs. 88% [38 of
      43 eyes in the PDT group], P = 0.48). Both treatments were associated with an
      increase of chorioretinal atrophy size, which was greater in the PDT-treated eyes
      (P = 0.016). CONCLUSION: Ranibizumab therapy showed a greater long-term efficacy
      compared with PDT in myopic CNV eyes, with a fewer proportion of eyes developing
      an increase of lesion and chorioretinal atrophy size.

PMID- 24946102
TI  - Central serous chorioretinopathy in patients receiving exogenous testosterone
      therapy.
AB  - PURPOSE: To report an association between central serous chorioretinopathy (CSCR)
      and exogenous testosterone therapy. METHODS: This is a retrospective case series
      from two institutions. Patients who presented with fluorescein angiography and
      optical coherence tomography findings consistent with CSCR were included. All
      patients were concurrently being treated with exogenous testosterone therapy and
      lacked other known risk factors for CSCR. RESULTS: Nine patients presented with
      CSCR after beginning exogenous testosterone therapy. Two patients stopped therapy
      with resolution of symptoms and subretinal fluid. CONCLUSION: Exogenous
      testosterone may be an independent risk factor for the development of CSCR.

PMID- 24946103
TI  - Use of ultra-wide-field retinal imaging in the management of active Behcet
      retinal vasculitis.
AB  - BACKGROUND: Retinal vasculitis (RV) is an important component of Behcet disease.
      It may be difficult to detect either clinically or with conventional retinal
      imaging. The role of ultra-wide-field (UWF) retinal imaging was assessed in the
      diagnosis and management of RV associated with Behcet disease. METHODS: A total
      of 38 eyes of 20 patients with active RV associated to Behcet disease underwent
      UWF imaging with the Optos scanning laser ophthalmoscope, fundus
      autofluorescence, and/or fluorescein angiography. This study determined the UWF
      findings and percentage of patients in whom this imaging modality assisted in
      diagnosing the extent of vasculitis, planning treatment, and monitoring disease
      activity. RESULTS: Optos UWF imaging assisted in diagnosing and quantifying the
      extent of RV in 16 patients (80%), planning medical treatment or laser
      photocoagulation in 13 of 20 patients (65%), and enhanced disease monitoring in
      11 of 20 patients (55%). UWF fluorescein angiography revealed vasculitis not
      clinically evident in 28 of 33 eyes (84.8%). Predominant angiographic findings
      were diffuse vascular leakage (75.7%), peripheral retinal nonperfusion (66.7%),
      optic disk leakage (63.6%), macular leakage (30.3%), and macular edema (27.3%).
      Eighteen patients (34 eyes) underwent UWF fundus autofluorescence, showing
      multiple hyperfluorescent spots in retinal periphery in 28 eyes (82.3%).
      CONCLUSION: Ultra-wide-field imaging is a valuable tool in the management of
      patients with RV associated to Behcet disease and can be used for the diagnosis,
      treatment, and follow-up. Additional studies, including longitudinal evaluations,
      are needed to elucidate whether these findings or the subsequent management
      alterations may improve patients' outcomes.

PMID- 24946105
TI  - Five-year cohort study: emphysematous progression of indium-exposed workers.
AB  - BACKGROUND: Dose-dependent adverse lung effects due to indium exposure have been
      reported in a cross-sectional study. This is a 5-year longitudinal cohort study
      of indium-exposed and unexposed workers, assessing indium exposure levels and its
      clinical lung effects. METHODS: From 2008 to 2011, a 5-year follow-up study was
      conducted on 40 unexposed and 240 workers formerly or currently exposed to indium
      at 11 factories. Indium exposure was assessed by serum indium (In-S) (MUg/L).
      Lung effects were assessed by subjective symptoms, serum biomarkers, spirometry,
      and chest high-resolution CT scan. Effect biomarkers used were Krebs von den
      Lungen and surfactant protein D. RESULTS: Mean values of In-S, Krebs von den
      Lungen, and surfactant protein D among the workers exposed to indium at baseline
      declined during the 5-year follow-up by 29.8%, 27.2%, and 27.5%, respectively. Of
      the exposed subjects with In-S levels > 20 MUg/L, 26.3% experienced emphysematous
      progression on high-resolution CT scan. Ninety percent (18 of 20) of workers with
      emphysematous progression during follow-up were current smokers at baseline, and
      a trend of increasing incidence of emphysematous progression at higher In-S
      levels was observed among the smokers (P = .005). Emphysematous changes among
      subjects with In-S levels > 20 MUg/L were likely to progress, after adjusting for
      age, mean duration since initial indium exposure, and smoking history (OR =
      10.49, 95% CI = 1.54-71.36). CONCLUSIONS: Long-term adverse effects on
      emphysematous changes were observed. The results suggest workers exposed to
      indium with In-S levels > 20 MUg/L should be immediately removed from exposure.

PMID- 24946106
TI  - The effect of level of straw bale provision on the behaviour and leg health of
      commercial broiler chickens.
AB  - This study aimed to assess the effect of the number of straw bales (SBs) provided
      on the behaviour and leg health of commercial broiler chickens. Houses containing
      ~23 000 broiler chickens were assigned to one of two treatments: (1) access to 30
      SBs per house, '30SB' or (2) access to 45 SB per house, '45SB'. This equated to
      bale densities of 1 bale/44 m2 and 1 bale/29 m2 of floor space within houses,
      respectively. Treatments were applied in one of two houses on a commercial farm,
      and were replicated over six production cycles. Both houses had windows and were
      also artificially lit. Behaviour was observed in weeks 3 to5 of the cycle. This
      involved observations of general behaviour and activity, gait scores (0: perfect
      to 5: unable to walk) and latency to lie (measured in seconds from when a bird
      had been encouraged to stand). Production performance and environmental
      parameters were also measured. SB density had no significant effect on activity
      levels (P>0.05) or walking ability (P>0.05). However, the average latency to lie
      was greater in 30SB birds compared with 45SB birds (P<0.05). The incidence of
      hock burn and podo dermatitis, average BW at slaughter and levels of mortality
      and culling were unaffected by SB density (P>0.05). The results from this study
      suggest that increasing SB levels from 1 bale/44 m2 to 1 bale/29 m2 floor space
      does not lead to significant improvements in the welfare of commercial broiler
      chickens in windowed houses.

PMID- 24946104
TI  - PKC inhibition results in a Kv 1.5 + Kv beta1.3 pharmacology closer to Kv 1.5
      channels.
AB  - BACKGROUND AND PURPOSE: The Kv beta1.3 subunit modifies the gating and
      pharmacology of Kv 1.5 channels in a PKC-dependent manner, decreasing channel
      sensitivity to bupivacaine- and quinidine-mediated blockade. Cardiac Kv 1.5
      channels associate with receptor for activated C kinase 1 (RACK1), the Kv beta1.3
      subunit and different PKC isoforms, resulting in the formation of a functional
      channelosome. The aim of the present study was to investigate the effects of PKC
      inhibition on bupivacaine and quinidine block of Kv 1.5 + Kv beta1.3 channels.
      EXPERIMENTAL APPROACH: HEK293 cells were transfected with Kv 1.5 + Kv beta1.3
      channels, and currents were recorded using the whole-cell configuration of the
      patch-clamp technique. PKC inhibition was achieved by incubating the cells with
      either calphostin C or bisindolylmaleimide II and the effects of bupivacaine and
      quinidine were analysed. KEY RESULTS: The voltage-dependent inactivation of Kv
      1.5 + Kv beta1.3 channels and their pharmacological behaviour after PKC
      inhibition with calphostin C were similar to those displayed by Kv 1.5 channels
      alone. Indeed, the IC50 values for bupivacaine were similar in cells whose PKC
      was inhibited with calphostin C or bisindolylmaleimide II. Similar results were
      also observed in the presence of quinidine. CONCLUSIONS AND IMPLICATIONS: The
      finding that the voltage-dependence of inactivation and the pharmacology of Kv
      1.5 + Kv beta1.3 channels after PKC inhibition resembled that observed in Kv 1.5
      channels suggests that both processes are dependent on PKC-mediated
      phosphorylation. These results may have clinical relevance in diseases that are
      characterized by alterations in kinase activity.

PMID- 24946107
TI  - [Sb(C6F5)4][B(C6F5)4]: an air stable, Lewis acidic stibonium salt that activates
      strong element-fluorine bonds.
AB  - As part of our ongoing interest in main group Lewis acids for fluoride anion
      complexation and element-fluorine bond activation, we have synthesized the
      stibonium borate salt [Sb(C6F5)4][B(C6F5)4] (3). The perfluorinated stibonium
      cation [Sb(C6F5)4](+) present in this salt is a potent Lewis acid which abstracts
      a fluoride anion from [SbF6](-) and [BF(C6F5)3](-) indicating that it is a
      stronger Lewis acid than SbF5 and B(C6F5)3. The unusual Lewis acidic properties
      of 3 are further reflected by its ability to polymerize THF or to promote the
      hydrodefluorination of fluoroalkanes in the presence of Et3SiH. While highly
      reactive in solution, 3 is a perfectly air stable salt, making it a convenient
      Lewis acidic reagent. 

PMID- 24946108
TI  - Twenty years of development of dual and multi-selector models in capillary
      electrophoresis: a review.
AB  - It has been 20 years since Lurie et al. first published their model of
      electromigration of an analyte under simultaneous interaction with two
      cyclodextrins as chiral selectors. Since then, the theory of (enantio)separation
      in dual and complex mixtures of (chiral) selectors is well understood. In spite
      of this, a trial-and-error approach still prevails in analytical practice. Such a
      situation is likely caused by the fact that the entire theory is spread over
      numerous papers and the relations between various models are not always clear.
      The present review condenses the theory for the first time. Available
      mathematical models and feasible practical approaches are summarized and their
      advantages and limitations discussed. 

PMID- 24946110
TI  - Safety of deferasirox: a retrospective cohort study on the risks of
      gastrointestinal, liver and renal events.
AB  - BACKGROUND: Deferasirox (DFX) is an effective and well-tolerated oral iron
      chelator elevating the adherence to iron chelating therapy among patients with
      iron overload. However, the US Food and Drug Administration issued a warning
      about the potential adverse events associated with DFX in 2010. METHODS: To
      examine the risks of gastrointestinal (GI) bleeding, acute liver necrosis, and
      acute renal failure among DFX users compared with desferrioxamine (DFO) users in
      a real-world setting, first-time users of DFX or DFO between 2005 and 2008 in
      Taiwan's National Health Insurance database were observed in this population
      based retrospective cohort study. The risks of different adverse events were
      individually analyzed by Cox proportional hazards models and adjusted by age,
      sex, concomitant medications, and prior medical conditions. RESULTS: Deferasirox
      users had the highest incidence rates of GI bleeding (2.03 per 10 000 patient
      days), acute liver necrosis (0.26 per 10 000 patient-days) and acute renal
      failure (1.45 per 10 000 patient-days) compared with other iron chelator users.
      Compared with DFO users, DFX users were not associated with the risk of GI
      bleeding (adjusted HR 1.03, 95% CI 0.61-1.74, p = 0.90) and the risk of acute
      liver necrosis (adjusted HR 2.13, 95% CI 0.49-9.33, p = 0.32). The association
      between DFX use and acute renal failure was found to be statistically significant
      (HR 2.18, 95% CI 1.18-4.02, p = 0.01; adjusted HR 2.41, 95% CI 1.27-4.58, p =
      0.01). CONCLUSION: In this study, we found statistically significant higher risk
      of acute renal failure and non-statistically significant higher risk of GI
      bleeding and acute liver necrosis associated with DFX use. More researches are
      warranted to evaluate the association between DFX use and potential adverse
      events.

PMID- 24946109
TI  - Surgical management of hepatic hemangiomas: a multi-institutional experience.
AB  - BACKGROUND: The management of hepatic hemangiomas remains ill defined. This study
      sought to investigate the indications, surgical management and outcomes of
      patients who underwent a resection for hepatic hemangiomas. METHODS: A
      retrospective review from six major liver centres in the United States
      identifying patients who underwent surgery for hepatic hemangiomas was performed.
      Clinico-pathological, treatment and peri-operative data were evaluated. RESULTS:
      Of the 241patients who underwent a resection, the median age was 46 years
      [interquartile range (IQR): 39-53] and 85.5% were female. The median hemangioma
      size was 8.5 cm (IQR: 6-12.1). Surgery was performed for abdominal symptoms
      (85%), increasing hemangioma size (11.3%) and patient anxiety (3.7%). Life
      threatening complications necessitating a hemangioma resection occurred in three
      patients (1.2%). Clavien Grade 3 or higher complications occurred in 14 patients
      (5.7%). The 30- and 90-day mortality was 0.8% (n = 2). Of patients with abdominal
      symptoms, 63.2% reported improvement of symptoms post-operatively. CONCLUSION: A
      hemangioma resection can be safely performed at high-volume institutions. The
      primary indication for surgery remains for intractable symptoms. The development
      of severe complications associated with non-operative management remains a rare
      event, ultimately challenging the necessity of additional surgical indications
      for a hemangioma resection.

PMID- 24946111
TI  - Theoretical study on molecular design and optical properties of organic
      sensitizers.
AB  - A series of organic sensitizers based on different configurations such as D-pi-A,
      D-[pi]n-A, D-pi-[A]n, [D]n-pi-A, D-pi-A-pi-D, D-pi-[A]n-pi-D and D-[pi-A]n-pi-D
      (where n = 1-4) are designed using theoretical methods. The effects of repeating
      pi-linker, donor-acceptor moieties and the substitution of additional donor
      acceptor moieties on the optoelectronic properties have been addressed. Our
      results show that the strength of the acceptor units changes the mono band
      absorption into dual band absorption in all the considered strategies. We found
      that repeating pi-linker/donor moieties in the D-pi-A series enhances the
      intensity of the absorption and can tune their absorption spectra from UV-to
      visible and visible to near IR regions by repeating acceptor units. Also, the
      present results indicate that the D-pi-A-pi-D configuration shows improved
      optical properties than the conventional D-pi-A structure. This theoretical study
      explores the new configurations and design strategies of organic dyes for
      developing efficient light harvesting devices working in the whole visible and
      near IR regions. 

PMID- 24946112
TI  - IL-8 gene variants are associated with lung function decline and multidimensional
      BODE index in COPD patients but not with disease susceptibility: a validation
      study.
AB  - BACKGROUND AND OBJECTIVE: COPD is a leading cause of dead worldwide and tobacco
      smoking is its major risk factor. IL8 is a proinflammatory chemokine mainly
      involved in the acute inflammatory reaction. The aim of this study was to test
      the association of IL-8, CXCR1 and CXCR2 gene variants and COPD susceptibility as
      part of a replication study and explore the effect of these variations in disease
      progression. METHODS: 9 tagSNPs were genotyped in 728 Caucasian individuals (196
      COPD patients, 80 smokers and 452 non-smoking controls). Pulmonary compromise was
      evaluated using spirometry and clinical parameters at baseline and annually over
      a 2 years period. We also determined plasma levels of TNF-alpha, IL-6, IL-8 and
      IL-16 in COPD patients. RESULTS: There was a lack of association between gene
      variants or haplotypes with predisposition to COPD. No correlation was observed
      between the polymorphisms and cytokines levels. Interestingly, significant
      associations were found between carriers of the rs4073A (OR = 3.53, CI 1.34-9.35,
      p = 0.01), rs2227306C (OR = 5.65, CI 1.75-18.88, p = 0.004) and rs2227307T (OR =
      4.52, CI = 1.49-12.82, p = 0.007) alleles in the IL-8 gene and patients who
      scored higher in the BODE index and showed an important decrease in their FEV1
      and FVC during the 2 years follow-up period (p < 0.05). CONCLUSIONS: Despite no
      association was found between the studied genes and COPD susceptibility, three
      polymorphisms in the IL-8 gene appear to be involved in a worse progression of
      the disease, with an affectation beyond the pulmonary function and importantly, a
      reduction in lung function along the follow-up years.

PMID- 24946114
TI  - Editorial.

PMID- 24946113
TI  - Methyl viologen responsive proteome dynamics of Anabaena sp. strain PCC7120.
AB  - A proteomic approach was employed to elucidate the response of an agriculturally
      important microbe, Anabaena sp. strain PCC7120, to methyl viologen (MV). Exposure
      to 2 MUM MV caused 50% lethality (LD50 ) within 6 h and modified the cellular
      levels of several proteins. About 31 proteins increased in abundance and 24
      proteins decreased in abundance, while 55 proteins showed only a minor change in
      abundance. Of these, 103 proteins were identified by MS. Levels of proteins
      involved in ROS detoxification and chaperoning activities were enhanced but that
      of crucial proteins involved in light and dark reactions of photosynthesis
      declined or constitutive. The abundance of proteins involved in carbon and energy
      biogenesis were altered. The study elaborated the oxidative stress defense
      mechanism deployed by Anabaena, identified carbon metabolism and energy
      biogenesis as possible major targets of MV sensitivity, and suggested potential
      biotechnological interventions for improved stress tolerance in Anabaena 7120. 

PMID- 24946115
TI  - Alexithymia and personality dimensions in relation to depression and anxiety in
      male alcohol-dependent inpatients.
AB  - Objective. The aim of this study was to determine the relationship of alexithymia
      and temperament and character model of personality with depression and anxiety
      symptoms in detoxified male alcohol-dependent inpatients. Method. The subjects
      consisted of 176 male alcohol-dependent inpatients according to the Diagnostic
      and Statistical Manual of Mental Disorders, 4th Edition. Patients were
      investigated with the Beck Depression Inventory, Beck Anxiety Inventory, State
      and Trait Anxiety Inventory, Michigan Alcoholism Screening Test (MAST), Toronto
      Alexithymia Scale (TAS-20) and Temperament and Character Inventory (TCI).
      Results. MAST score and scores of all three factors of the TAS-20 significantly
      predicted depression scale and anxiety scales. Difficulty in identifying feelings
      and difficulty in describing feelings factors were particularly effective,
      relative to the externally orientated thinking factor of the TAS-20 for
      prediction depression and anxiety. The TCI dimensions emerged as distinct and
      conceptually meaningful predictors for the depression scale and anxiety scales.
      Conclusion. Depression and anxiety symptoms among detoxified male alcohol
      dependents are associated with alexithymia, a broad range of personality
      dimensions and higher severity of alcohol-related problems, which make these
      related factors highly relevant for clinical practice. 

PMID- 24946116
TI  - Benzhexol-dependence resulting from self-medication for intermittent explosive
      disorder.
AB  - Objective. Recent observations in Iraq during the period of sanction suggest the
      existence of benzhexol prescribing linked to its calming effects on explosive
      behaviours. This inspired our group to research the existence of this practice
      and the characteristics of those involved in it. Method. All patients from the
      psychiatric service in Merjan Hospital, Al Hilla City, Babylon Governate, Iraq,
      who had a prescription for benzhexol between January 1991 and December 2000, were
      identified. All participants received their diagnosis based on the clinical
      criteria of the DSM-IV, after taking a comprehensive medical and psychiatric
      history, mental state examination and collateral information from family members.
      The patients were evaluated by the same qualified consultant psychiatrist at the
      initial assessment and all through the period of follow-up. Results. In the 10
      year period under study, 354 patients were prescribed benzhexol. A total of 190
      patients diagnosed as intermittent explosive disorder (IED) and 164 suffering
      from severe mental disorders or personality disorders were excluded from the
      study. The average age of the IED group was 29.5 years. On direct questioning,
      the main reason patients gave most frequently for using benzhexol was to control
      the aggressive outbursts (N=92, 48.4), to get high (N=49, 25.8), to relax (N=26,
      13.7), to get rid of boredom (N=23, 12.1). In total, the whole group were
      prescribed benzhexol, at an average dose of 12.5 mg/day (range 2-20 mg/day). At
      the time of final assessment the mean dose of prescribed benzhexol had fallen
      slightly to 12 mg/day (2-20 mg/day), with 10 patients being benzhexol free. Of
      the 190, three patients had a diagnosis of obsessive compulsive disorders, 36
      patients had a diagnosis of benzodiazepines dependence, and a further five had a
      diagnosis of alcohol dependency syndrome. Eighty percent felt satisfied with the
      effect of the drug and 95 were not motivated to stop it. Conclusions. There are a
      significant number of patients who are routinely prescribed benzhexol as a
      replacement therapy. The main original reason for starting it is to control
      outbursts and improves their reaction to stress situations. This growing issue
      raises the need for awareness, by both public and medical practitioners, of the
      potential adverse effects of benzhexol and its untoward consequences. 

PMID- 24946117
TI  - Are age-related trends in suicide rates associated with life expectancy and socio
      economic factors?
AB  - Background. A recent cross-national study reported that suicide rates increased,
      decreased or remained unchanged with increasing age in individual countries. The
      relationship between age-related trends in suicide rates and child mortality
      rates, life expectancy and socio-economic factors was examined. Methods.
      Countries with an increase, decrease and no change in suicide rates with
      increasing age were ascertained from an earlier study (Shah, 2007a, International
      Psychogeriatrics, 19, 1141), which analysed data from the World Health
      Organisation (WHO). The relationship between age-related trends in suicide rates
      and (i) child mortality rates, (ii) life expectancy and (iii) markers of socio
      economic status (per capita gross national domestic product (GDP) and the Gini
      coeffcient) was examined using data from the WHO and the United Nations. Results.
      The main findings were: (i) child mortality rates were significantly lower in
      countries with an increase in suicide rates with increasing age when compared to
      countries without a change in suicide rates with increasing age in males; (ii)
      life expectancy was significantly higher in countries with an increase in suicide
      rates with increasing age when compared to countries without a change in suicide
      rates with increasing age in males; and (iii) the Gini coefficient was
      significantly lower in countries with an increase in suicide rates with
      increasing age when compared to countries without a change or a decline in
      suicide rates with increasing age in females. Conclusions. Potential explanations
      for these findings and the interaction of life expectancy and socio-economic
      factors with other factors that differentially influence suicide rates in
      different age and sex groups requires further examination. 

PMID- 24946118
TI  - Fluctuating plasma levels of the active moiety of risperidone is related to
      occurrence of extrapyramidal symptoms.
AB  - In the present study, we compared the plasma levels of the active moiety (i.e.
      risperidone plus 9-hydroxyrisperidone) in a steady state in 54 Japanese
      schizophrenic patients with or without emerging extrapyramidal symptoms (EPS and
      non-EPS groups, respectively) who were treated with 4 mg/day risperidone. No
      differences were observed in the plasma levels of the active moiety at 4 and 8
      weeks after risperiodne administration in both groups. However, the EPS group
      patients showed a greater number of fluctuations/larger fluctuations in the
      plasma active moiety levels than those in the non-EPS group. These results
      suggest that a stable plasma active moiety level maybe important for preventing
      EPSs during treatment with risperidone. 

PMID- 24946119
TI  - Childhood traumatic events and dissociation in university students.
AB  - Objective. The purpose of this study was to determine the frequency of childhood
      traumatic events, to investigate its relationship with dissociation and other
      psychiatric symptoms and to examine the potential effect of family functioning on
      dissociative symptoms and general psychopathology in a Turkish university student
      sample. Methods. All participant completed Brief Physical and Sexual Abuse
      Questionnaire, Symptom Checklist-90-Revised (SCL-90-R), Dissociative Experiences
      Scale (DES) and Family Assessment Device (FAD). Results. The most frequent
      childhood trauma type was separation from caretaker (46.1%). Witnessing violence
      (33.1%), harsh punishment (21.2%) and substance abuse in family (10.5%) followed.
      Sexual abuse of incest type was seen in 6.3%. Students who reported childhood
      traumatic events had higher DES and SCL-90-R scores compared to those who did
      not. There were fair relationships between SCL-90-R and FAD scores. Conclusion. A
      history of childhood traumatic events may be related to increased level of
      dissociation and general psychopathology in university students. Other pathogenic
      family factors also may contribute to the development of psychiatric symptoms. 

PMID- 24946120
TI  - Affective temperaments and residual symptoms in patients with mood and anxiety
      disorders.
AB  - Objective. Temperament conventionally refers to stable behavioural and emotional
      reactions that appear early in life and are influenced in part by genetic
      constitution. Few studies compared temperamental traits in anxiety and mood
      disorders even though some authors suggested a clinical and neurobiological
      continuum between them. The aim of the study was to compare temperamental traits
      and psychopathological dimensions in subjects with DSM-IV diagnoses of mood and
      anxiety disorders. Methods. A total of 101 clinically stabilized consecutive
      outpatients (45 subjects with anxiety disorders and 56 with mood disorders
      diagnoses) were evaluated. The brief version of Temperament Evaluation of
      Memphis, Pisa, Paris and San Diego (briefTEMPS-M) and Symptom Checklist-90 (SCL
      90) were used to assess temperamental traits and psychopathological dimensions,
      respectively. Results. No significant differences between anxiety disorders and
      mood disorders subjects for TEMPS-M or SCL-90 mean scores were observed.
      Different TEMPS-M scores differentially affect residual clinical symptoms.
      Conclusions. Our data represent an indirect indicator of possible common
      diathesis between the two different disorders. The temperament "paradigm" could
      explain part of the residual symptomatology. The evaluation of affective
      temperaments seems to add considerable clinical information to psychopathological
      and diagnostic descriptions. 

PMID- 24946121
TI  - Dosing patterns in Europe: Efficacy and safety of risperidone long-acting
      injectable in doses of 25, 37.5 and 50 mg.
AB  - Objective. To assess the dose prescription patterns for risperidone long-acting
      injectable (RLAI) in patients with schizophrenia who participated in the 6-month,
      open-label Switch to Risperidone Microspheres (StoRMi) trial. Methods. Clinically
      stable patients requiring a change in medication were converted to RLAI
      prescribed using clinically-appropriate doses, as determined by treating
      clinicians. RLAI 25 mg was recommended as the starting dose, although higher
      initiation doses were permitted if deemed necessary. RLAI was administered
      intramuscularly every 2 weeks, with dosage adjustments permitted, and continued
      for a total of 6 months. Efficacy outcomes included Positive and Negative
      Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). Treatment
      emergent adverse events (AEs) were monitored. Results. A total of 1,849 patients
      were included. Modal dose was 25 mg for 52.9% of patients. At baseline, patients
      treated with lower RLAI doses were more likely to be female, have shorter disease
      duration, milder symptoms, and be using less polypharmacy. The strongest
      predictors that a patient would remain on 25 mg RLAI were baseline PANSS
      hallucinatory behaviour item score (odds ratio [OR]=0.78), baseline CGI-S score
      (OR=0.69), female gender (OR=1.56), and country of residence (P<0.001 for all).
      Efficacy measures improved in all dose groups, with the greatest improvement seen
      in patients treated with lower doses. AEs were more common in patients treated
      with 50 mg RLAI (68 vs. 57% with lower doses; P<0.0001), although most AEs were
      mild to moderate in severity. Conclusion. In this study, 25 mg RLAI was the most
      commonly prescribed dose. RLAI was effective and well tolerated over the full
      range of doses. 

PMID- 24946122
TI  - NAPSAQ-1: National Patient Sleep Assessment Questionnaire in depression.
AB  - Objectives. Sleep disturbance is a common feature of depression. Symptoms often
      persist after treatment of the depressive episode, representing a risk factor for
      relapse. There is a lack of data regarding the nature of sleep disturbance in
      depression in the UK. Methods. We surveyed patients' views about their depressive
      symptoms and associated sleep difficulties. We received 513 responses via postal
      questionnaire. Results. A total of 97% reported sleep difficulties during
      depression: symptoms of insomnia were more frequently reported than hypersomnia.
      Ninety-nine percent of those with sleep problems also reported daytime symptoms
      including lack of concentration, exhaustion and lethargy, no energy and feeling
      sleepy; 40% admitted napping during the day; 59% indicated that poor sleep
      greatly affected their quality of life (QOL); 34% considered it to be "very
      distressing"; 69% of respondents were taking antidepressant medication at the
      time (44% said it improved their sleep, 56% said it had no effect or worsened
      their sleep); 69% had sought extra treatment for their sleep problems.
      Conclusions. Sleep disturbance in depression is a common and distressing problem
      that seems relatively unresolved by treatment. There is a need for more
      successful management in order to improve QOL in these patients and reduce a
      factor in depressive relapse. 

PMID- 24946123
TI  - Cost effectiveness analysis of escitalopram compared to venlafaxine and
      fluvoxamine in treatment of major depressive disorder.
AB  - Objective. To compare the costs and effectiveness of escitalopram with
      venlafaxine and fluvoxamine for treatment of major depressive disorder (MDD) from
      the societal perspective in Singapore. Methods. The decision analytical model
      consisted of two pathways, one for primary care and the other for secondary care
      over a time horizon of 6 months. The parameters in the model were derived from
      clinical trials and results of a survey on local general practitioners and
      psychiatrists. The proportion of patients successfully treated was the main
      effectiveness measurement. Both direct and indirect costs were estimated and
      reported in 2007 Singapore dollars. Deterministic and probabilistic sensitivity
      analyses were performed. Results. The overall success rate for the 6-month
      treatment was 68.1% for escitalopram compared to 66.0% for venlafaxine. The total
      costs per patient treated were $2845 for escitalopram compared to $3176 for
      venlafaxine. The overall success rate was 64.7% for escitalopram and 60.0% for
      fluvoxamine. The total costs per patient treated were $3133 for escitalopram
      compared to $3297 for fluvoxamine. Probability sensitivity analysis demonstrated
      that escitalopram was dominant to venlafaxine and fluvoxamine in more than 95% of
      the random samples. Conclusion. Escitalopram is a cost-effective pharmacotherapy
      for MDD compared to venlafaxine and fluvoxamine. 

PMID- 24946124
TI  - Relationship between adjunctive medications for anxiety and time spent ill in
      patients with bipolar disorder.
AB  - Objective. Many patients with bipolar disorder take adjunctive medications for
      anxiety. Using naturalistic data, we investigated the relationship between the
      use of adjunctive anxiolytics and the time spent in episodes or with subsyndromal
      mood symptoms. Methods. This was a post-hoc analysis of 310 patients with bipolar
      disorder who previously recorded mood and medications daily for 5 months using
      ChronoRecord software. One hundred patients were taking adjunctive anxiolytics
      for at least 50% of days; 210 were not. Of the 100 patients, 73 were taking a
      benzodiazepine. All patients taking anxiolytics were also receiving treatments
      for bipolar disorder. Results. Patients with bipolar disorder who were taking
      adjunctive medications for anxiety spent more time ill. Comparing patients who
      were taking or not taking anxiolytics, the mean days spent either in any episode
      or with subsyndromal symptoms was 45.6 vs. 29.6%, respectively (P<0.001), the
      mean days in any episode was 17.1 vs. 9.2%, respectively (P=0.016), and the mean
      days with subsyndromal depression was 26.4 vs. 16.2%, respectively (P=0.004).
      Conclusion. While this methodology cannot determine causality, these findings
      highlight the need for controlled studies of the long-term impact of adjunctive
      medications for anxiety on mood symptoms in patients being treated for bipolar
      disorder. 

PMID- 24946125
TI  - Executive dysfunction in Korsakoff's syndrome: Time to revise the DSM criteria
      for alcohol-induced persisting amnestic disorder?
AB  - Objective. This study examines the profile of executive dysfunction in
      Korsakoff's syndrome. There is accumulating evidence of executive deficits in
      Korsakoff patients that may greatly affect activities of daily living. However,
      the DSM-IV criteria for "alcohol-induced persisting amnestic disorder" do not
      take this into account. In addition, existing studies have failed to determine
      the type of executive deficits in this syndrome. Methods. Executive functioning
      was assessed in 20 Korsakoff patients using the Behavioural Assessment of the
      Dysexecutive Syndrome (BADS), an ecologically valid neuropsychological assessment
      battery consisting of various subtests that assess planning, organisation,
      inhibition, shifting, cognitive estimation and monitoring. Results. Sixteen
      patients (80%) had executive deficits, i.e. impairments on at least one BADS
      subtest compared to a normative control group. Overall, the profile is
      characterized by planning deficits on unstructured tasks. Conclusions. Next to
      amnesia, executive deficits are a prominent characteristic of cognitive
      impairment in Korsakoff patients. It is argued that the new DSM criteria should
      consider incorporating executive dysfunction as an important feature of alcohol
      induced persistent cognitive disorder. 

PMID- 24946126
TI  - A possible relationship between Toxoplasma gondii and schizophrenia: A
      seroprevalence study.
AB  - Objective. Schizophrenia is a pervasive neuropsychiatric disease of uncertain
      etiology. We aimed to investigate a possible association between Toxoplasma
      gondii infection and schizophrenia in this study. Method. We selected individuals
      with schizophrenia (n=88) and tested them with commercially available enzyme
      linked immunosorbent assay (ELISA) for anti-Toxoplasma IgG and IgM antibodies and
      compared these seropositivity rate to those of controls without psychiatric
      disease (n=88). Results. The rate of IgG antibody in the schizophrenia patients
      (47.7%) was higher than the control groups (20.4%) (P<0.001). We did not find any
      anti-Toxoplasma IgM seropositivity in both schizophrenia patients and control
      group. In schizophrenic patients with and without anti-Toxoplasma IgG groups
      statistical analysis did not reveal any correlation between demographic variables
      and Toxoplasma infection. Conclusion. Our findings supported previous studies
      indicate that T.gondii may play a role in etiopathogenesis in some cases of
      schizophrenia. 

PMID- 24946127
TI  - Progression of posturographic findings after acquired brain injury.
AB  - OBJECTIVE: To study the characteristics of balance performance in a sample of
      patients with increasing postural instability after acquired brain injury (ABI)
      and to establish the clinical utility of a new computerized posturographic system
      (NedSVE/IBV). METHODS: This study included 108 patients with ABI divided into
      five groups from minimal to severe postural impairment. All patients were
      assessed with the NedSVE/IBV system and with traditional balance measures.
      Posturographic analyses included the modified clinical test of sensory
      interaction on balance, the limits of stability and the weight-shifting test.
      Sensitivity to detect changes and reproducibility were evaluated in 63 patients
      who were followed-up for 6 months and in 20 patients who were evaluated on two
      separate occasions during the same week, respectively. RESULTS: The patients
      showed reduced stability limits, abnormal postural responses and an increased
      reliance on visual input with differences in intensity directly related to their
      degree of balance impairment. Posturographic study showed excellent convergent
      validity, reproducibility and sensitivity to detect changes. CONCLUSION: The data
      suggests that, regardless of the intensity of postural instability, there is a
      common mechanism of sensory processing to maintain balance after ABI. The NedSVE
      IBV system is a valid tool to quantify balance after ABI.

PMID- 24946128
TI  - Influence of very short patch mismatch repair on SOS inducing lesions after
      aminoglycoside treatment in Escherichia coli.
AB  - Low concentrations of aminoglycosides induce the SOS response in Vibrio cholerae
      but not in Escherichia coli. In order to determine whether a specific factor
      present in E. coli prevents this induction, we developed a genetic screen where
      only SOS inducing mutants are viable. We identified the vsr gene coding for the
      Vsr protein of the very short patch mismatch repair (VSPR) pathway. The effect of
      mismatch repair (MMR) mutants was also studied. We propose that lesions formed
      upon aminoglycoside treatment are preferentially repaired by VSPR without SOS
      induction in E. coli and by MMR when VSPR is impaired. 

PMID- 24946129
TI  - The influence of bilateral sagittal split ramus osteotomy on submental-cervical
      aesthetics.
AB  - The effect of orthodontic-surgical treatment on submental-cervical region was
      evaluated in a very limited number of studies. The aim of this study was to
      evaluate submental-cervical soft tissue contour changes following mandibular
      advancement and set-back procedures via bilateral sagittal split ramus osteotomy.
      Sixty-seven patients were included in this study. Group 1 consisted of 27
      skeletal Class II patients who underwent mandibular advancement surgery, whereas
      Group 2 consisted of 40 skeletal Class III patients who underwent mandibular set
      back surgery. Various linear and angular measurements were performed on pre
      operative and sixth month post-operative cephalometric radiographs. A new method
      was used to evaluate the amount of sagging at submental region. The submental
      length did not change in Group 1; however, it decreased significantly in Group 2
      (P < 0.05). The angle between submental plane and facial plane decreased to 95.9
      degrees  from 98.8 degrees  in Group 1(P < 0.05), whereas it increased to 93.1
      degrees  from 88.2 degrees  in Group2 (P < 0.05). The change of submental soft
      tissue sag was almost stable in Group 1, while 0.34 mm increase of sag was
      observed in Group 2. This increase was not statistically significant (P > 0.05).
      Mandibular set-back and advancement procedures do not remarkably change the
      submental sag following approximately 6 mm jaw movement. Although mandibular
      advancement did not significantly effect submental length, soft tissue followed
      mandibular set-back with a ratio of 1:1 at C-point to projection of soft tissue
      pogonion and 1:0.7 at C-point to soft tissue menton distances.

PMID- 24946130
TI  - Mussel-inspired, perfluorinated polydopamine for self-cleaning coating on various
      substrates.
AB  - We designed a perfluorinated dopamine derivative, which, upon oxidative
      polymerization, formed a structurally rough film of extremely low surface energy
      on various substrates. The static water contact angles larger than 150 degrees 
      and the low water sliding angles less than 7 degrees  confirmed the formation of
      superhydrophobic, self-cleaning surfaces. 

PMID- 24946131
TI  - Cu(2)ZnSnS(4)-Pt and Cu(2)ZnSnS(4)-Au heterostructured nanoparticles for
      photocatalytic water splitting and pollutant degradation.
AB  - Cu2ZnSnS4, based on abundant and environmental friendly elements and with a
      direct band gap of 1.5 eV, is a main candidate material for solar energy
      conversion through both photovoltaics and photocatalysis. We detail here the
      synthesis of quasi-spherical Cu2ZnSnS4 nanoparticles with unprecedented narrow
      size distributions. We further detail their use as seeds to produce CZTS-Au and
      CZTS-Pt heterostructured nanoparticles. Such heterostructured nanoparticles are
      shown to have excellent photocatalytic properties toward degradation of Rhodamine
      B and hydrogen generation by water splitting. 

PMID- 24946133
TI  - Immunohistochemical study of tubular epithelial cells and vascular endothelial
      cells in glomerulonephritis.
AB  - BACKGROUND AND AIMS: In order to assess the role played by tubular epithelial
      cells (TEC) and interstitial vascular endothelial cells (VEC) in interstitial
      fibrogenesis in human glomerulonephritis, we studied the expression of markers of
      activated fibroblasts (alpha-smooth muscle actin (alphaSMA) and vimentin (Vim))
      and of the transforming growth factor beta (TGFbeta), at the level of these
      cells. METHODS: We studied retrospectively 41 renal biopsies from patients with
      primary and secondary glomerulonephritis [24 males, 17 females, mean age 45.5 +/-
      12.9 years]. Immunohistochemistry using monoclonal antibodies (SMA, Vim, TGFbeta)
      was assessed using a semiquantitative score, that was correlated with biological
      and histological data (quantified using a scoring system in order to assess
      active-inflammatory and chronic-sclerotic/fibrotic lesions). RESULTS: The
      presence of SMA and Vim as markers of myofibroblasts was found in TECs and VECs.
      TEC Vim expression correlated with interstitial Vim expression (r = 0.38; p =
      0.008), interstitial infiltrate (r = 0.31; p = 0.027), interstitial fibrosis (R =
      0.25; p = 0.042), GFR (r = -0.35; p = 0.016), SMA (r = -0.42; p = 0.015), TGFbeta
      (r = 0.25; p = 0.046), and hemoglobin (r = -0.55; p < 0.001). VEC Vim expression
      showed indirect correlations with interstitial infiltrate (r = -0.32; p = 0.023)
      and interstitial fibrosis (r = -0.34; p = 0.017). CONCLUSION: Our study reflects
      the complexity of the involvement of VEC and mainly of TEC in fibrosis. The
      expression of mesenchymal markers at the tubular cell level (especially Vim)
      correlates with histological interstitial changes, with the decrease of renal
      function and more strongly with anemia.

PMID- 24946134
TI  - Radiation sensitization of tumor cells induced by shear stress: the roles of
      integrins and FAK.
AB  - Recent studies revealed that the interstitial fluid flow in and around tumor
      tissue not only played an important role in delivering anticancer agents, but
      also affected the microenvironment, mostly hypoxia, in modulating tumor radio
      sensitivity. The current study investigated the hypoxia-independent mechanisms of
      flow-induced shear stress in sensitizing tumors to radiation. Colon cancer cells
      were seeded onto glass slides pre-coated with fibronectin. A parallel-plate flow
      chamber system was used to impose fluid shear stress. Cell proliferation,
      apoptosis and colony assays were measured after shear stress and/or radiation.
      Cell cycle analysis and immunoblots of cell adhesion signal molecules were
      evaluated. The effect of shear stress was reversed by modulating integrin beta1
      or FAK. Shear stress of 12dyne/cm(2) for 24h, but not 3h, enhanced the radiation
      induced cytotoxicity to colon cancer cells. Protein expression of FAK was
      significantly down-regulated but not transcriptionally suppressed. By modulating
      integrin beta1 and FAK expression, we demonstrated that shear stress enhanced
      tumor radiosensitivity by regulating integrin beta1/FAK/Akt as well as integrin
      beta1/FAK/cortactin pathways. Shear stress in combination with radiation might
      regulate integrins signaling by recruiting and activating caspases 3/8 for FAK
      cleavage followed by ubiquitin-mediated proteasomal degradation. Shear stress
      enhanced the radiation toxicity to colon cancer cells through suppression of
      integrin signaling and protein degradation of FAK. The results of our study
      provide a strong rationale for cancer treatment that combines between radiation
      and strategy in modulating tumor interstitial fluid flow. 

PMID- 24946136
TI  - Weaning children off enteral nutrition by netcoaching versus onsite treatment: a
      comparative study.
AB  - AIM: The Graz model of tube weaning has been internationally recognised as a
      successful and rapid tube weaning program. Beside the onsite treatment option, a
      telemedical counselling was specifically developed in 2009. This study aims to
      show outcomes of this newly invented treatment in a large sample of patients.
      METHODS: Our retrospective open-label study compared success of onsite versus
      telemedical Graz-based weaning methods for patients with diverse clinical
      diagnoses with either nasogastric, gastric or jejunal tubes. Outcome variables
      were successful transition to oral feeds, partial transition to night tube feeds,
      and failure or interruption of intervention. Patients and physicians chose the
      intervention method. RESULTS: Complete weaning was achieved in 153 of 169 (90.5%)
      children in the netcoaching group versus 170 of 209 (81.3%) of those opting for
      onsite treatment (no significant differences, P > 0.05). Higher partial weaning
      rates were observed in the onsite group (15.3% vs. 4.7%, P < 0.01, degrees of
      freedom = 3, chi(2) = 22.76). There were no significant differences regarding the
      outcomes 'weaning trial without success' (netcoaching: 0% vs. onsite: 2.9%, P >
      0.05) and 'interruption of programme' (netcoaching: 4.7% vs. onsite: 0.5%, P >
      0.05) between the two groups. CONCLUSION: Despite limitations of study design, we
      have demonstrated similar efficacy of Graz-based less expensive netcoaching
      versus more expensive onsite intervention in a large referral population with
      chronic tube dependency with the majority transitioning to complete oral feeds.

PMID- 24946137
TI  - Poloxamer-based curcumin solid dispersions for ex tempore preparation of
      supersaturated solutions intended for antimicrobial photodynamic therapy.
AB  - Abstract Phototoxic effect of curcumin supersaturated solutions toward pathogenic
      bacteria has already been demonstrated. However, to be useful in the clinical
      practice, a supersaturated solution needs to be physically and chemically stabile
      over the relevant time period. Poloxamer-based solid dispersions (SD) intended
      for ex tempore preparation of a supersaturated solution were designed to
      simultaneously facilitate dissolution and inhibit precipitation of curcumin in
      vitro. Due to the transformation of the crystalline compound to an amorphous
      form, as shown by X-ray powder diffraction, the desired concentration of curcumin
      could easily be achieved upon hydration of SDs. The efficiency of selected
      poloxamers (Pluronic(r) F-127, F-68 and P-123) as the precipitation inhibitors
      (PIs) and influence of an additional PI (polyethylene glycol 400, hydroxypropyl
      methylcellulose, and hyaluronic acid) on the physical stability of the solutions
      were examined by UV-Vis spectrophotometry. HPLC-PDA was employed to evaluate
      hydrolytic and photolytic stability of curcumin in the SD solutions. At sub
      micellar concentrations, Pluronics(r) F-127 and P-123, but not F-68, delayed
      curcumin precipitation in aqueous media and protected the compound from
      hydrolytic degradation up to 24 h. Complete inactivation of Enterococcus faecalis
      was achieved after exposure to solutions of selected SDs at curcumin
      concentration >=1 uM and the light dose of 9.4 J/cm2.

PMID- 24946135
TI  - Signaling components of the 1alpha,25(OH)2D3-dependent Pdia3 receptor complex are
      required for Wnt5a calcium-dependent signaling.
AB  - Wnt5a and 1alpha,25(OH)2D3 are important regulators of endochondral ossification.
      In osteoblasts and growth plate chondrocytes, 1alpha,25(OH)2D3 initiates rapid
      effects via its membrane-associated receptor protein disulfide isomerase A3
      (Pdia3) in caveolae, activating phospholipase A2 (PLA2)-activating protein
      (PLAA), calcium/calmodulin-dependent protein kinase II (CaMKII), and PLA2,
      resulting in protein kinase C (PKC) activation. Wnt5a initiates its calcium
      dependent effects via intracellular calcium release, activating PKC and CaMKII.
      We investigated the requirement for components of the Pdia3 receptor complex in
      Wnt5a calcium-dependent signaling. We determined that Wnt5a signals through a
      CaMKII/PLA2/PGE2/PKC cascade. Silencing or blocking Pdia3, PLAA, or vitamin D
      receptor (VDR), and inhibition of calmodulin (CaM), CaMKII, or PLA2 inhibited
      Wnt5a-induced PKC activity. Wnt5a activated PKC in caveolin-1-silenced cells, but
      methyl-beta-cyclodextrin reduced its stimulatory effect. 1alpha,25(OH)2D3 reduced
      stimulatory effects of Wnt5a on PKC in a dose-dependent manner. In contrast,
      Wnt5a had a biphasic effect on 1alpha,25(OH)2D3-stimulated PKC activation;
      50ng/ml Wnt5a caused a 2-fold increase in 1alpha,25(OH)2D3-stimulated PKC but
      higher Wnt5a concentrations reduced 1alpha,25(OH)2D3-stimulated PKC activation.
      Western blots showed that Wnt receptors Frizzled2 (FZD2) and Frizzled5 (FZD5),
      and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were localized to
      caveolae. Blocking ROR2, but not FZD2 or FZD5, abolished the stimulatory effects
      of 1alpha,25(OH)2D3 on PKC and CaMKII. 1alpha,25(OH)2D3 membrane receptor complex
      components (Pdia3, PLAA, caveolin-1, CaM) interacted with Wnt5a receptors/co
      receptors (ROR2, FZD2, FZD5) in immunoprecipitation studies, interactions that
      changed with either 1alpha,25(OH)2D3 or Wnt5a treatment. This study demonstrates
      that 1alpha,25(OH)2D3 and Wnt5a mediate their effects via similar receptor
      components and suggests that these pathways may interact. 

PMID- 24946138
TI  - Effect of Recombinant Human Growth Hormone on Osseointegration of Titanium
      Implants: A Histologic and Biomechanical Study in Rabbits.
AB  - To evaluate the action of recombinant human growth hormone (rhGH) on
      osseointegration of titanium implants in rabbits. Fourteen adult New Zealand
      rabbits, aged 30 weeks, were used in the study, and randomly divided into 2
      groups. In each animal, 2 (2.2 mm * 6 mm) pure titanium implants were placed in
      the left tibia. In one group (test group), 1 IU (0.3 mg) of rhGH as a lyophilized
      powder was applied to each osteotomy site prior to implant placement. Only
      titanium implants were placed in osteotomy sites of the other group (control).
      Animals were humanely killed at 14 and 42 days after surgery, and samples were
      then prepared for histologic analysis and biomechanical test. The biomechanical
      test showed tensile pull-out stress values of 33.88 N/cm(2) for controls and
      59.26 N/cm(2) for the rhGH group at 14 days and 25.99 N/cm(2) and 29.69 N/cm(2)
      for the control and the test group, respectively, at 42 days. Scanning electron
      microscope analysis showed more uniform and abundant bone tissue in contact with
      the implants for the test group at 14 days, and no differences between groups at
      42 days. Furthermore, histologic analysis also showed accelerated bone repair in
      14 days and a more advanced stage of bone remodeling for the rhGH-treated group
      when compared to controls after 42 days of repair. Such results show that the
      topical use of rhGH induces new bone formation in the early stages of bone repair
      and hence accelerates osseointegration of titanium dental implants. 

PMID- 24946139
TI  - Why don't some men with banked sperm respond to letters about their stored
      samples?
AB  - Abstract Long-term storage of banked sperm, especially when it is not needed, for
      reproductive purposes, is costly and poses practical problems for sperm banks.
      For sperm banks to function efficiently, men must understand the implications of
      unnecessary storage, and make timely decisions about disposal of their own
      samples. Men who bank sperm prior to cancer treatment are routinely offered
      follow-up consultations to test their fertility, update consent and, where
      necessary, expedite referral for Assisted Conception. Yet sperm banks report that
      men do not respond to letters, suggesting samples are stored needlessly. We
      conducted semi-structured interviews with six men with a history of not
      responding to letters, to document reasons for non-response. Interviews were
      transcribed and analysed using Interpretive Phenomenological Analysis. Men's
      reasons for not responding are a complex interplay between past, present and
      future perspectives. In terms of their past, information is important on
      diagnosis, because men must understand that fertility can change after treatment.
      Present and future concerns focus on fears of being told fertility has not
      recovered and being pressured to dispose of banked sperm. The challenge is to
      devise invitation letters that address men's concerns while offering them
      tangible benefits and peace of mind. 

PMID- 24946140
TI  - Polypharmacology: challenges and opportunities in drug discovery.
AB  - At present, the legendary magic bullet, i.e., a drug with high potency and
      selectivity toward a specific biological target, shares the spotlight with an
      emerging and alternative polypharmacology approach. Polypharmacology suggests
      that more effective drugs can be developed by specifically modulating multiple
      targets. It is generally thought that complex diseases such as cancer and central
      nervous system diseases may require complex therapeutic approaches. In this
      respect, a drug that "hits" multiple sensitive nodes belonging to a network of
      interacting targets offers the potential for higher efficacy and may limit
      drawbacks generally arising from the use of a single-target drug or a combination
      of multiple drugs. In this review, we will compare advantages and disadvantages
      of multitarget versus combination therapies, discuss potential drug promiscuity
      arising from off-target effects, comment on drug repurposing, and introduce
      approaches to the computational design of multitarget drugs. 

PMID- 24946144
TI  - Tailoring the mechanics of ultrathin carbon nanomembranes by molecular design.
AB  - Freestanding carbon nanomembranes (CNMs) with a thickness between 0.6 and 1.7 nm
      were prepared from self-assembled monolayers (SAMs) of diverse polyaromatic
      precursors via low-energy electron-induced cross-linking. The mechanical
      properties of CNMs were investigated using AFM bulge test, where a pressure
      difference was applied to the membrane and the resulting deflection was measured
      by atomic force microscopy. We found a correlation between the rigidity of the
      precursor molecules and the macroscopic mechanical stiffness of CNMs. While CNMs
      from rigid and condensed precursors like naphthalene and pyrene thiols prove to
      exhibit higher Young's moduli of 15-19 GPa, CNMs from nonfused oligophenyls
      possess lower Young's moduli of ~10 GPa. For CNMs from less densely packed SAMs,
      the presence of defects and nanopores plays an important role in determining
      their mechanical properties. The finite element method (FEM) was applied to
      examine the deformation profiles and simulate the pressure-deflection
      relationships.

PMID- 24946142
TI  - The application of solid-state NMR spectroscopy to study candesartan cilexetil
      (TCV-116) membrane interactions. Comparative study with the AT1R antagonist drug
      olmesartan.
AB  - AlphaTau1 receptor (AT1R) antagonists exert their antihypertensive effects by
      preventing the vasoconstrictive hormone AngII to bind to the AT1 receptor. It has
      been proposed that these biological effects are mediated through a two-step
      mechanism reaction. In the first step, they are incorporated in the core of the
      lipid bilayers and in the second step they reach the active site of the receptor
      through lateral diffusion. In this model, drug/membrane interactions are key
      elements for the drugs achieving inhibition at the AT1 receptor. In this work,
      the interactions of the prodrug candesartan cilexetil (TCV-116) with lipid
      bilayers are studied at molecular detail. Solid-state (13)C-CP/MAS, 2D (1)H-(1)H
      NOESY NMR spectroscopy and in silico calculations are used. TCV-116 and
      olmesartan, another drug which acts as an AT1R antagonist are compared for their
      dynamic effects in lipid bilayers using solid-state (2)H-NMR. We find a similar
      localization of TCV-116 compared to other AT1 antagonists in the intermediate
      polar region. In addition, we can identify specific local interactions. These
      interactions may be associated in part with the discrete pharmacological profiles
      observed for different antagonists. 

PMID- 24946143
TI  - Palmitoylation of STREX domain confers cerebroside sensitivity to the BKCa
      channel.
AB  - Our previous study reported that cerebrosides from traditional Chinese medicine
      Baifuzi directly interact with the STREX domain of BKCa channels, which in turn
      results in the therapeutic effect of Baifuzi on ischemic stroke. However, it is
      not known how cerebrosides in the plasma membrane could interact with the STREX
      domain that is in the cytoplasmic side. Using patch-clamp technique, effects of
      different cerebrosides on the BKCa channel were studied by measuring single
      channel currents in CHO cells expressing wild type or mutated BKCa channels.
      Palmitoylation of the STREX domain was removed either by site-directed
      mutagenesis or pharmacological inhibition. Removal of palmitoylation sites at
      C646 and C647 by mutating the residues to Ala abolished the ability of
      cerebrosides to activate the BKCa channel. In contrast, the mutation neither
      changed the single channel conductance nor voltage sensitivity of the channel.
      Both palmitoylation inhibitors tunicamycin and palmitic acid analog 2
      bromopalmitate attenuated the activation of the BKCa channel by cerebrosides.
      Furthermore, confocal images on STREX-EGFP fragments demonstrated that STREX
      fragments no longer associated with the plasma membrane when the palmitoylation
      was removed or blocked. These findings suggest that palmitoylation of the STREX
      domain is necessary for cerebrosides to activate the BKCa channel and provide
      insight into the mechanism of how Baifuzi could exert therapeutic effect on
      ischemic stroke. 

PMID- 24946141
TI  - Elastic deformation and area per lipid of membranes: atomistic view from solid
      state deuterium NMR spectroscopy.
AB  - This article reviews the application of solid-state 2H nuclear magnetic resonance
      (NMR) spectroscopy for investigating the deformation of lipid bilayers at the
      atomistic level. For liquid-crystalline membranes, the average structure is
      manifested by the segmental order parameters (SCD) of the lipids. Solid-state 2H
      NMR yields observables directly related to the stress field of the lipid bilayer.
      The extent to which lipid bilayers are deformed by osmotic pressure is integral
      to how lipid-protein interactions affect membrane functions. Calculations of the
      average area per lipid and related structural properties are pertinent to bilayer
      remodeling and molecular dynamics (MD) simulations of membranes. To establish
      structural quantities, such as area per lipid and volumetric bilayer thickness, a
      mean-torque analysis of 2H NMR order parameters is applied. Osmotic stress is
      introduced by adding polymer solutions or by gravimetric dehydration, which are
      thermodynamically equivalent. Solid-state NMR studies of lipids under osmotic
      stress probe membrane interactions involving collective bilayer undulations,
      order-director fluctuations, and lipid molecular protrusions. Removal of water
      yields a reduction of the mean area per lipid, with a corresponding increase in
      volumetric bilayer thickness, by up to 20% in the liquid-crystalline state.
      Hydrophobic mismatch can shift protein states involving mechanosensation,
      transport, and molecular recognition by G-protein-coupled receptors. Measurements
      of the order parameters versus osmotic pressure yield the elastic area
      compressibility modulus and the corresponding bilayer thickness at an atomistic
      level. Solid-state 2H NMR thus reveals how membrane deformation can affect
      protein conformational changes within the stress field of the lipid bilayer.

PMID- 24946145
TI  - Bismuth nitrate-induced novel nitration of estradiol: an entry to new anticancer
      agents.
AB  - Direct nitration of estradiol was carried out using metal nitrates on solid
      surfaces under mild condition, and a combination of bismuth nitrate pentahydrate
      impregnated KSF clay was found to be the best reagent to synthesize 2- and 4
      nitroestradiol effectively. Furthermore, various basic side chains were
      introduced, through O-linker at C-3, to these nitroestradiols. The ability of
      these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER
      negative breast cancer cell lines, as well as cancer cell lines of other origins,
      was examined. Qualitative structure activity relationship (SAR) has also been
      studied. We found that a basic side chain containing either a piperidine or
      morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective
      at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly,
      this effective cytotoxicity was even seen in ER-negative breast cancer cells. 

PMID- 24946146
TI  - Biological evaluation of new nickel(II) metallates: Synthesis, DNA/protein
      binding and mitochondrial mediated apoptosis in human lung cancer cells (A549)
      via ROS hypergeneration and depletion of cellular antioxidant pool.
AB  - A series of novel nickel(II) thiosemicarbazone complexes(1-4) have been prepared
      and characterized by various spectral, analytical techniques and X-ray
      crystallography. Further, their efficacy to interact with CT-DNA/BSA has been
      explored. From the binding studies, it is inferred that complex 4 found to be
      more active than other complexes. The complexes bound with CT-DNA by
      intercalation mode. Moreover, static quenching was observed for their interaction
      with BSA. The new complexes were tested for their in vitro cytotoxicity against
      human lung adenocarcinoma (A549) cell line. The results showed that the new
      complexes exhibited significant degree of cytotoxicity at given experimental
      condition. Further, the results of LDH and NO release supported the cytotoxic
      nature of the complexes. The observed cytotoxicity of the complexes may be routed
      through ROS-hypergeneration and lipid-peroxidation with subsequent depletion of
      cellular antioxidant pool (GSH, SOD, CAT, GPx and GST) resulted in the reduction
      of mitochondrial-membrane potential, caspase-3 activation and DNA fragmentation.
      Thus, the data from the present study disclose that the complexes could induce
      apoptosis in A549 cells through mitochondrial mediated fashion and inhibited the
      migration of lung cancer cells and by metastasis.

PMID- 24946147
TI  - Molecularly imprinted polymer for specific extraction of hypericin from Hypericum
      perforatum L. herbal extract.
AB  - The molecularly imprinted polymers (MIPs) were prepared by an oxidation-reduction
      polymerization system using a non-covalent molecularly imprinting strategy with
      hypericin as the template, acrylamide as the functional monomer and
      pentaerythritol triacrylate as the cross-linker in the porogen of acetone. The UV
      spectrum revealed that a cooperative hydrogen-bonding complex between hypericin
      and acrylamide might be formed at the ratio of 1:6 in the prepolymerized system.
      Two classes of the binding sites were produced in the resulting hypericin
      imprinted polymer with the dissociation constants of 16.61MUgL(-1) and 69.35MUgL(
      1), and the affinity binding sites of 456.53MUgg(-1) and 603.06MUgg(-1),
      respectively. The synthesized MIPs were characterized by scanning electron
      microscope, thermogravimetric and differential thermal analysis. High-performance
      liquid chromatography was used to investigate the adsorption and recognition
      properties of the MIPs. Selective binding of the template molecule was
      demonstrated in comparison to the analog pseudohypericin. After the Hypericum
      perforatum L. plant being air dried and finely ground, an extract was prepared by
      shaking the powder in a methanol-water solution (80:20, v/v), vacuum filtration
      though a Buchner funnel, liquid-liquid extraction with ethyl ether and ethyl
      acetate, and evaporating on a rotary evaporator until dry. With the sorbents of
      the optimized MIPs, a molecularly imprinted solid-phase extraction (MISPE)
      procedure was developed for enrichment and separation of hypericin from the
      Hypericum extract in the presence of interfering substances. The selective
      extraction of hypericin from herbal medicine was achieved with the recovery of
      82.30%. The results showed that MISPE can be a useful tool for specific isolation
      and effective clean-up of target compounds from natural products. 

PMID- 24946148
TI  - Suppression of peak tailing of phosphate prodrugs in reversed-phase liquid
      chromatography.
AB  - Peak tailing of phosphate prodrugs in acidic mobile phases was thoroughly
      investigated. The results indicated that both metal-phosphate interactions and
      silanophilic interactions contributed to the observed peak tailing. Column
      pretreatment with phosphate buffers was demonstrated to be an effective and
      robust approach in suppressing metal-phosphate interaction. Silanophilic
      interactions, such as hydrogen bonding interactions between protonated isolated
      silanol groups and partially deprotonated phosphate groups were mobile phase pH
      dependent. The combination of column pretreatment and volatile low pH mobile
      phase buffers can be used to mitigate peak tailing issues in developing MS
      compatible RPLC methods for phosphate prodrugs. The use of non-endcapped columns
      should be avoided in RPLC analysis for phosphate prodrugs due to large amount of
      residual silanol groups in the stationary phases. 

PMID- 24946149
TI  - Novel orthogonal liquid chromatography methods to dose neurotransmitters involved
      in Parkinson's disease.
AB  - Parkinson's disease is a multifactorial neurodegenerative disorder, characterized
      by a reduction of dopamine (DA) levels. The molecular pathways involved in the
      pathogenesis of disease have not yet been fully disclosed. Therefore, developing
      new diagnostic methods and tools to evaluate the depletion of DA and of some of
      its metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3
      methoxytyramine) is of outstanding importance for biochemical evaluations.
      Moreover, neurons responsible for DA release also produce the neurotransmitter
      gamma-aminobutyric acid (GABA), thus, quantitative measurements of GABA levels
      can have a relevant impact for a further understanding of the biochemical
      processes involved in the neurodegenerative event. In the present study, two HPLC
      methods based on the reversed-phase ion-pairing chromatography (RP-IPC) and the
      hydrophilic liquid interaction chromatography (HILIC) concepts were developed to
      allow the quantification of DA and its metabolites as well as GABA levels in
      mouse striatal and cortical tissue homogenates. The two fairly orthogonal HPLC
      methods were directly applied to the biological samples, without preliminary
      derivatization of the compounds of interest. A high level of selectivity was
      obtained for DA metabolites and GABA by running the gradient RP-IPC method with a
      volatile ion-pairing reagent, which makes it suitable for the quantitative assay
      of four out of five compounds. Matrix deriving interferences unabled the base
      line separation of DA which was instead successfully achieved with the HILIC
      based method. To avail of HPLC methods providing distinct selectivity profiles,
      makes possible the correct species quantification and allows to compensate the
      intrinsic limits characterizing all chromatographic methods. 

PMID- 24946150
TI  - Undesigned selection for replication termination of bacterial chromosomes.
AB  - The oriC DNA replication origin in bacterial chromosomes, the location of which
      appears to be physically identified, is genetically regulated by relevant
      molecular machinery. In contrast, the location of the terminus remains obscure
      for many bacterial replicons, except for terC, the proposed and well-studied
      chromosome termination site in certain bacteria. The terC locus, which is
      composed of specific sequences for its binding protein, is located at a site
      opposite from oriC, exhibiting a symmetric structure around the oriC-terC axis.
      Here, we investigated Bacillus subtilis 168 strains whose axes were hindered and
      found that the native terC function was robust. However, eradication of terminus
      region specific binding protein resulted in the natural terC sites not being used
      for termination; instead, new termini were selected at a location exactly
      opposite to oriC. We concluded that replication generally terminates at the loci
      where the two approaching replisomes meet. This site was automatically selected,
      and two replisomes moving at the same rate supported symmetrical chromosome
      structures relative to oriC. The rule, which was even validated by artificial
      chromosomes irrespective of oriC, should be general for replicons administered by
      two replisomes. 

PMID- 24946151
TI  - Topology, dimerization, and stability of the single-span membrane protein CadC.
AB  - Under acid stress, Escherichia coli induce expression of CadA (lysine
      decarboxylase) and CadB (lysine/cadaverine antiporter) in a lysine-rich
      environment. The ToxR-like transcriptional activator CadC controls expression of
      the cadBA operon. Using a novel signal peptidase I (SPase I) cleavage assay, we
      show that CadC is a type II single-span membrane protein (S-SMP) with a
      cytoplasmic DNA-binding domain and a periplasmic sensor domain. We further show
      that, as long assumed, dimerization of the sensor domain is required for
      activating the cadBA operon. We prove this using a chimera in which the
      periplasmic domain of RodZ-a type II membrane protein involved in the maintenance
      of the rod shape of E. coli-replaces the CadC sensor domain. Because the RodZ
      periplasmic domain cannot dimerize, the chimera cannot activate the operon.
      However, replacement of the transmembrane (TM) domain of the chimera with the
      glycophorin A TM domain causes intramembrane dimerization and consequently operon
      activation. Using a low-expression protocol that eliminates extraneous TM helix
      dimerization signals arising from protein over-expression, we enhanced
      dramatically the dynamic range of the beta-galactosidase assay for cadBA
      activation. Consequently, the strength of the intramembrane dimerization of the
      glycophorin A domain could be compared quantitatively with the strength of the
      much stronger periplasmic dimerization of CadC. For the signal peptidase assay,
      we inserted an SPase I cleavage site (AAA or AQA) at the periplasmic end of the
      TM helix. Cleavage occurred with high efficiency for all TM and periplasmic
      domains tested, thus eliminating the need for the cumbersome spheroplast
      proteinase K method for topology determinations. 

PMID- 24946152
TI  - Non-invasive 13C-glucose breath test using residual gas analyzer-mass
      spectrometry: a novel tool for screening individuals with pre-diabetes and type 2
      diabetes.
AB  - We report, for the first time, the clinical feasibility of a novel residual gas
      analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C
      glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2
      diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in
      blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the
      Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic
      cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over
      baseline (DOB) value, was determined to be deltaDOB(13)C0/00 = 28.810/00 for
      screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD),
      corresponding to a sensitivity of 100% and specificity of 94.4%. We also
      determined another optimal diagnostic cut-off point of deltaDOB(13)C0/00 =
      19.880/00 between individuals with PD and T2D, which exhibited 100% sensitivity
      and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a
      typical diagnostic positive and negative predictive value of 96% and 100%,
      respectively. The diagnostic accuracy, precision and validity of the results were
      also confirmed by high-resolution optical cavity enhanced integrated cavity
      output spectroscopy (ICOS) measurements. The deltaDOB(13)C0/00 values measured
      with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by
      the laser based ICOS method. Moreover, we observed that the effects of endogenous
      CO2 production related to basal metabolic rates in individuals were statistically
      insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings
      suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C
      GBT which may serve as an alternative non-invasive point-of-care diagnostic tool
      for routine clinical practices as well as for large-scale diabetes screening
      purposes in real-time. 

PMID- 24946153
TI  - The translational potential of research on the ethical, legal, and social
      implications of genomics.
AB  - Federally funded research on the ethical, legal, and social implications (ELSI)
      of genomics includes a programmatic charge to consider policy-relevant questions
      and to communicate findings in venues that help inform the policy-making process.
      In addressing this goal, investigators must consider the range of policies that
      are relevant to human genetics; how foundational research in bioethics, law, and
      the social sciences might inform those policies; and the potential professional
      issues that this translational imperative raises for ELSI investigators. We
      review these questions in light of experiences from a consortium of federally
      funded Centers of Excellence in ELSI Research, and offer a set of policy
      recommendations for program design and evaluation of ELSI research. We conclude
      that it would be a mistake to require that ELSI research programs demonstrate a
      direct impact on science or health policy; however, ELSI researchers can take
      steps to increase the relevance of their work to policy makers. Similarly,
      funders of ELSI research who are concerned with facilitating policy development
      can help by building cross-disciplinary translational research capacities, and
      universities can take steps to make policy-relevant research more rewarding for
      scholars in the humanities, social sciences, and law.

PMID- 24946154
TI  - A systematic review and critical assessment of 11 discordant meta-analyses on
      reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in
      clopidogrel users.
AB  - We systematically investigated how 11 overlapping meta-analyses on the
      association between CYP2C19 loss-of-function alleles and clinical efficacy of
      clopidogrel could yield contradictory outcomes. The results of the meta-analyses
      differed because more recent meta-analyses included more primary studies and some
      had not included conference abstracts. Conclusions differed because between-study
      heterogeneity and publication bias were handled differently across meta-analyses.
      All meta-analyses on the clinical end point observed significant heterogeneity
      and several reported evidence for publication bias, but only one out of eight
      statistically significant meta-analyses concluded that therefore the association
      was unproven and one other refrained from quantifying a pooled estimate because
      of heterogeneity. For the end point stent thrombosis, all meta-analyses reported
      statistically significant associations with CYP2C19 loss-of-function alleles with
      no statistically significant evidence for heterogeneity, but only three had
      investigated publication bias and also found evidence for it. One study therefore
      concluded that there was no evidence for an association, and one other doubted
      the association because of a high level of heterogeneity. In summary, meta
      analyses on the association between CYP2C19 loss-of-function alleles and clinical
      efficacy of clopidogrel differed widely with regard to assessment and
      interpretation of heterogeneity and publication bias. The substantial
      heterogeneity and publication bias implies that personalized antiplatelet
      management based on genotyping is not supported by the currently available
      evidence.Genet Med advance online publication 19 June 2014. 

PMID- 24946155
TI  - Characteristics associated with genetic counseling referral and BRCA1/2 testing
      among women in a large integrated health system.
AB  - BACKGROUND: Evidence shows underutilization of cancer genetics services. To
      explore the reasons behind this underutilization, this study evaluated
      characteristics of women who were referred for genetic counseling and/or had
      undergone BRCA1/2 testing. METHODS: An ovarian cancer risk perception study
      stratified 16,720 eligible women from the Henry Ford Health System into average-,
      elevated-, and high-risk groups based on family history. We randomly selected
      3,307 subjects and interviewed 2,524 of them (76.3% response rate). RESULTS:
      Among the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%,
      respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%,
      respectively, reported having undergone BRCA testing. Personal breast cancer
      history, high risk, and perceived ovarian cancer risk were associated with both
      referral and testing. Discussion of family history with a doctor predicted
      counseling referral, whereas belief that family history influenced risk was the
      strongest BRCA testing predictor. Women perceiving their cancer risk as much
      higher than other women their age were twice as likely (95% confidence interval:
      2.0-9.6) to report genetic counseling referral. CONCLUSION: In a health system
      with ready access to cancer genetic counseling and BRCA testing, women who were
      at high risk underutilized these services. There were strong associations between
      perceived ovarian cancer risk and genetic counseling referral, and between a
      belief that family history influenced risk and BRCA testing.

PMID- 24946157
TI  - Molecular testing for the BRCA1 and BRCA2 Ashkenazi Jewish founder mutations: a
      report on the College of American Pathologists proficiency testing surveys.
AB  - PURPOSE: The purpose of this study was to analyze laboratory performance on
      proficiency testing surveys offered jointly by the College of American
      Pathologists/American College of Medical Genetics and Genomics biannually for the
      three common Ashkenazi Jewish founder mutations in the BRCA1 and BRCA2 genes.
      METHODS: Survey responses were analyzed for accuracy of genotype determination
      and the associated clinical interpretation. Data on an individual laboratory's
      participation over time, number of samples tested, turnaround time, and test
      methodology were also reviewed. RESULTS: Between 2003 and 2012, 23 US
      laboratories and 39 international laboratories participated. There were six
      genotyping errors, with a corresponding analytical sensitivity of 99.0% (479/484
      challenges; 95% confidence interval: 97.6-99.7%) and an analytic specificity of
      99.9% (870/871; 95% confidence interval: 99.4-99.9%). Among the 1,325 clinical
      interpretations, 92.5% (1,226/1,325; 95% confidence interval: 91.0-93.9%) matched
      the intended response. Most of the 99 discrepancies-81% (80/99)-incorrectly
      interpreted the risk for a negative test result as having a lifetime risk of
      breast cancer "that is the same as that in the general population" instead of
      "that cannot be determined without BRCA mutation testing of the affected
      relative." CONCLUSION: Clinical laboratories demonstrated excellent analytical
      sensitivity and specificity. The clinical interpretation requires additional
      education, focusing on the clinical interpretation of negative test results for
      these three mutations.

PMID- 24946156
TI  - Evidence synthesis and guideline development in genomic medicine: current status
      and future prospects.
AB  - PURPOSE: With the accelerated implementation of genomic medicine, health-care
      providers will depend heavily on professional guidelines and recommendations.
      Because genomics affects many diseases across the life span, no single
      professional group covers the entirety of this rapidly developing field. METHODS:
      To pursue a discussion of the minimal elements needed to develop evidence-based
      guidelines in genomics, the Centers for Disease Control and Prevention and the
      National Cancer Institute jointly held a workshop to engage representatives from
      35 organizations with interest in genomics (13 of which make recommendations).
      The workshop explored methods used in evidence synthesis and guideline
      development and initiated a dialogue to compare these methods and to assess
      whether they are consistent with the Institute of Medicine report "Clinical
      Practice Guidelines We Can Trust." RESULTS: The participating organizations that
      develop guidelines or recommendations all had policies to manage guideline
      development and group membership, and processes to address conflicts of
      interests. However, there was wide variation in the reliance on external reviews,
      regular updating of recommendations, and use of systematic reviews to assess the
      strength of scientific evidence. CONCLUSION: Ongoing efforts are required to
      establish criteria for guideline development in genomic medicine as proposed by
      the Institute of Medicine.

PMID- 24946158
TI  - Comprehensive identification of active triterpenoid metabolites in frankincense
      using a coupling strategy.
AB  - Frankincense resins are extensively used as natural remedies in regions ranging
      from North Africa to China. Triterpenoid metabolites from frankincense exhibit
      notable anti-inflammatory and anti-tumor properties. In the present paper,
      without the use of an isolation process, the fragmentation rules and NMR spectral
      characteristics of triterpenoid metabolites in frankincense are summarized
      through a coupling method using high performance liquid chromatography-diode
      array detection/electrospray ionization tandem mass spectrometry (HPLC-DAD/ESI
      MS(n)) combined with HPLC-nuclear magnetic resonance (NMR) experiments. Based on
      this groundwork, a coupling strategy for the comprehensive metabolic profiling of
      active triterpenoid metabolites from enriched fractions of frankincense was
      developed. The proposed strategy may serve as a method for the holistic screening
      of bioactive metabolites in complex TCM samples. 

PMID- 24946159
TI  - Comment on "multitissue molecular, genomic, and developmental effects of the
      deepwater horizon oil spill on resident Gulf killifish (Fundulus grandis)".

PMID- 24946161
TI  - Self-assembly in an evaporating nanofluid droplet: rapid transformation of
      nanorods into 3D fibre network structures.
AB  - Upon evaporation, ZnO nanorods in a nanofluid droplet undergo rapid and
      spontaneous chemical and morphological transformation into centimetre-long
      Zn(OH)2 fibres, via a mechanism very different from that for coffee rings. We
      show that the detailed nanostructure and micromorphology in the residual thin
      film depend intricately on the ambient moisture, nanofluid solvent composition
      and substrate surface chemistry. Upon thermal annealing, these Zn(OH)2 fibres
      readily undergo further chemical and morphological transformation, forming
      nanoporous fibres with the pore size tuneable by temperature. Our results point
      to a simple route for generating a self-assembled 3D structure with ultralong and
      nanoporous ZnO/Zn(OH)2 fibres/belts, and may also be of interest to the fields of
      evaporation controlled dynamic self-assembly, non-equilibrium crystallisation,
      and flow and fingering instabilities in nanofluids. 

PMID- 24946162
TI  - Novel proteomic biomarker panel for prediction of aggressive metastatic
      hepatocellular carcinoma relapse in surgically resectable patients.
AB  - The natural course of early HCC is unknown, and its progression to intermediate
      and advanced HCC can be diverse. Some early stage HCC patients enjoy prolonged
      disease-free survival, whereas others suffer aggressive relapse to stage IV
      metastatic cancer within a year. Comparative proteomics of HCC tumor tissues was
      carried out using 2D-DIGE and MALDI-TOF/TOF MS to identify proteins that can
      distinguish these two groups of stage I HCC patients. Twelve out of 148
      differentially regulated protein spots were found to differ by approximately 2
      fold for the relapse versus nonrelapse patient tissues. Four proteins, namely,
      heat shock 70 kDa protein 1, argininosuccinate synthase, isoform 2 of UTP-glucose
      1-phosphate uridylyltransferase, and transketolase, were shown to have the
      potential to differentiate metastatic relapse (MR) from nonrelapse (NR) HCC
      patients after validation by western blotting and immunohistochemical assays.
      Subsequent TMA analysis revealed a three marker panel of HSP70, ASS1, and UGP2 to
      be statistically significant in stratifying the two groups of HCC patients. This
      combination panel achieved high levels of sensitivity and specificity, which has
      potential for clinical use in identifying HCC tumors prone to MR. This
      stratification will allow development of clinical management, including close
      follow-up and possibly treatment options, in the near future. 

PMID- 24946160
TI  - Copper binding in IscA inhibits iron-sulphur cluster assembly in Escherichia
      coli.
AB  - Among the iron-sulphur cluster assembly proteins encoded by gene cluster iscSUA
      hscBA-fdx in Escherichia coli, IscA has a unique and strong iron binding activity
      and can provide iron for iron-sulphur cluster assembly in proteins in vitro.
      Deletion of IscA and its paralogue SufA results in an E. coli mutant that fails
      to assemble [4Fe-4S] clusters in proteins under aerobic conditions, suggesting
      that IscA has a crucial role for iron-sulphur cluster biogenesis. Here we report
      that among the iron-sulphur cluster assembly proteins, IscA also has a strong and
      specific binding activity for Cu(I) in vivo and in vitro. The Cu(I) centre in
      IscA is stable and resistant to oxidation under aerobic conditions. Mutation of
      the conserved cysteine residues that are essential for the iron binding in IscA
      abolishes the copper binding activity, indicating that copper and iron may share
      the same binding site in the protein. Additional studies reveal that copper can
      compete with iron for the metal binding site in IscA and effectively inhibits the
      IscA-mediated [4Fe-4S] cluster assembly in E. coli cells. The results suggest
      that copper may not only attack the [4Fe-4S] clusters in dehydratases, but also
      block the [4Fe-4S] cluster assembly in proteins by targeting IscA in cells.

PMID- 24946163
TI  - Trace metal concentration and fish size: variation among fish species in a
      Mediterranean river.
AB  - Concentration of trace metals (Al, Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb and As) in the
      muscle of six fish species was analyzed to determine the variation with fish size
      and fish species in an Iberian river with moderate metal pollution. Al, Fe and Zn
      were the most abundant metals across sites. Fish size and sampling site explained
      more variation than fish species, and a high intraspecific variability (among
      individuals) in metal loads was also observed. Considering the most spread
      species, concentrations were highest in bleak (Alburnus alburnus) and lowest in
      gudgeon (Gobio occitaniae) for all the elements. Metal loads were comparable with
      literature data from contaminated sites, often exceeding recommended European
      Environmental Quality Standards. The relationships between metal concentration
      and fish size varied markedly among sites, elements, and fish species. The slopes
      of these relationships were often significantly heterogeneous, a fact barely
      acknowledged in the literature, and were often negative, probably due to size
      specific metabolic rates related to fish growth.

PMID- 24946164
TI  - Validation of the cochlear implant artifact correction tool for auditory
      electrophysiology.
AB  - Auditory event-related potentials (ERPs) collected from cochlear implant (CI)
      users are often contaminated by large electrical device-related artifacts. Using
      independent component analysis (ICA), the artifacts can be manually identified
      and removed, and the ERP responses can be reconstructed from the remaining
      components. Viola et al. [17] recently developed an efficient algorithm that uses
      spatial and temporal statistics of the components to automate CI artifact
      removal. The purpose of this study was to perform an independent validation of
      the algorithm. We further assessed whether the ERP responses were stable over the
      course of one year when analyzed manually or using the semi-automated approach.
      To achieve these aims, we collected EEG data from 6 adult CI users at two
      sessions, with one year between each session. We compared their ERP responses
      reconstructed using the algorithm and the manual approach. We found no
      significant differences when comparing the two approaches to removing CI artifact
      across sessions, validating the use of the semi-automated method. 

PMID- 24946167
TI  - A gold exchange: a mechanistic study of a reversible, formal ethylene insertion
      into a gold(III)-oxygen bond.
AB  - The Au(III) complex Au(OAc(F))2(tpy) (1, OAc(F) = OCOCF3; tpy = 2-p
      tolylpyridine) undergoes reversible dissociation of the OAc(F) ligand trans to C,
      as seen by (19)F NMR. In dichloromethane or trifluoroacetic acid (TFA), the
      reaction between 1 and ethylene produces Au(OAc(F))(CH2CH2OAc(F))(tpy) (2). The
      reaction is a formal insertion of the olefin into the Au-O bond trans to N. In
      TFA this reaction occurs in less than 5 min at ambient temperature, while 1 day
      is required in dichloromethane. In trifluoroethanol (TFE),
      Au(OAc(F))(CH2CH2OCH2CF3)(tpy) (3) is formed as the major product. Both 2 and 3
      have been characterized by X-ray crystallography. In TFA/TFE mixtures, 2 and 3
      are in equilibrium with a slight thermodynamic preference for 2 over 3. Exposure
      of 2 to ethylene-d4 in TFA caused exchange of ethylene-d4 for ethylene at room
      temperature. The reaction of 1 with cis-1,2-dideuterioethylene furnished
      Au(OAc(F))(threo-CHDCHDOAc(F))(tpy), consistent with an overall anti addition to
      ethylene. DFT(PBE0-D3) calculations indicate that the first step of the formal
      insertion is an associative substitution of the OAc(F) trans to N by ethylene.
      Addition of free (-)OAc(F) to coordinated ethylene furnishes 2. While
      substitution of OAc(F) by ethylene trans to C has a lower barrier, the kinetic
      and thermodynamic preference of 2 over the isomer with CH2CH2OAc(F) trans to C
      accounts for the selective formation of 2. The DFT calculations suggest that the
      higher reaction rates observed in TFA and TFE compared with CH2Cl2 arise from
      stabilization of the (-)OAc(F) anion lost during the first reaction step. 

PMID- 24946168
TI  - meso-Aryl core-modified fused sapphyrins: syntheses and structural diversity.
AB  - Two new, fused core-modified expanded porphyrins, sapphyrins 3 and 4, were
      synthesized by a simple acid-catalyzed condensation of electron-rich and rigid
      precursor, dithienothiophene (DTT) diol, and core-modified tripyrrane. These
      sapphyrins exhibit structural diversity depending upon the heteroatom present in
      the macrocyclic framework, where the thiophene ring is inverted in 3, while the
      selenophene ring in 4 exists in normal and inverted form in the free base and
      addition of two protons shifts the equilibrium to inverted form. 

PMID- 24946166
TI  - Variation in enteric methane emissions among cows on commercial dairy farms.
AB  - Methane (CH4) emissions by dairy cows vary with feed intake and diet composition.
      Even when fed on the same diet at the same intake, however, variation between
      cows in CH4 emissions can be substantial. The extent of variation in CH4
      emissions among dairy cows on commercial farms is unknown, but developments in
      methodology now permit quantification of CH4 emissions by individual cows under
      commercial conditions. The aim of this research was to assess variation among
      cows in emissions of eructed CH4 during milking on commercial dairy farms.
      Enteric CH4 emissions from 1964 individual cows across 21 farms were measured for
      at least 7 days/cow using CH4 analysers at robotic milking stations. Cows were
      predominantly of Holstein Friesian breed and remained on the same feeding systems
      during sampling. Effects of explanatory variables on average CH4 emissions per
      individual cow were assessed by fitting a linear mixed model. Significant effects
      were found for week of lactation, daily milk yield and farm. The effect of milk
      yield on CH4 emissions varied among farms. Considerable variation in CH4
      emissions was observed among cows after adjusting for fixed and random effects,
      with the CV ranging from 22% to 67% within farms. This study confirms that
      enteric CH4 emissions vary among cows on commercial farms, suggesting that there
      is considerable scope for selecting individual cows and management systems with
      reduced emissions. 

PMID- 24946165
TI  - Anti-IL-31 receptor antibody is shown to be a potential therapeutic option for
      treating itch and dermatitis in mice.
AB  - BACKGROUND AND PURPOSE: IL-31, which is described as a pruritogenic cytokine, is
      linked to the itching that is associated with allergic and non-allergic eczema,
      but the precise pruritogenic mechanism of IL-31 and its potential as a
      therapeutic target for atopic dermatitis (AD) have not been determined.
      EXPERIMENTAL APPROACH: We investigated the effects of existing drugs on the
      scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL
      31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL
      31 receptor alpha subunit (anti-IL-31 receptor alpha) neutralizing antibody on
      chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL
      31 not only induces scratching behaviour, but is also the causative factor in an
      AD phenotype. KEY RESULTS: The scratching behaviour induced by an i.v. injection
      of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor alpha
      neutralizing antibody. In contrast, it was not inhibited significantly by a non
      sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and
      tacrolimus), or a MU-opioid receptor antagonist (naloxone). The anti-IL-31
      receptor alpha-neutralizing antibody reduced the ear swelling and dermatitis
      score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the
      anti-IL-31 receptor alpha-neutralizing antibody showed therapeutic effects on the
      dermatitis even if it was injected after the disease had developed. CONCLUSIONS
      AND IMPLICATIONS: Anti-IL-31 receptor alpha is a potential novel therapeutic
      approach for escaping from the itch-scratch cycle and also a treatment for
      dermatitis in AD.

PMID- 24946169
TI  - Start-up of electrophoresis of an arbitrarily oriented dielectric cylinder.
AB  - An analytical study is presented for the transient electrophoretic response of a
      circular cylindrical particle to the step application of an electric field. The
      electric double layer adjacent to the particle surface is thin but finite
      compared with the radius of the particle. The time-evolving electroosmotic
      velocity at the outer boundary of the double layer is utilized as a slip
      condition so that the transient momentum conservation equation for the bulk fluid
      flow is solved. Explicit formulas for the unsteady electrophoretic velocity of
      the particle are obtained for both axially and transversely applied electric
      fields, and can be linearly superimposed for an arbitrarily-oriented applied
      field. If the cylindrical particle is neutrally buoyant in the suspending fluid,
      the transient electrophoretic velocity is independent of the orientation of the
      particle relative to the applied electric field and will be in the direction of
      the applied field. If the particle is different in density from the fluid, then
      the direction of electrophoresis will not coincide with that of the applied field
      until the steady state is attained. The growth of the electrophoretic mobility
      with the elapsed time for a cylindrical particle is substantially slower than for
      a spherical particle.

PMID- 24946171
TI  - Complex reconstruction of a massive shoulder and chest wall defect: de-bone
      appetit flap.
AB  - We report the use of a fillet of upper arm pedicled flap, which has not been
      previously reported in the literature. The fillet of upper arm flap follows the
      principle of "spare parts" surgery, and can provide vascularized soft tissue
      coverage for defects of the shoulder and the chest wall when the upper extremity
      cannot otherwise be salvaged, such as in cases of radical tumor excision. The
      fillet of upper arm pedicled flap was used to successfully cover a large shoulder
      and chest wall defect measuring 25 cm x 15 cm. This "spare parts" reconstructive
      technique has several advantages over the previously reported forearm free flap,
      including minimal need for microsurgery and the ability for expansion to cover
      larger defects. This case demonstrates effective use of fillet of upper arm flaps
      in reconstruction of large defects of the shoulder and chest wall. 

PMID- 24946173
TI  - Pneumatosis Intestinalis of the Small Bowel; Radiological and Intra-operative
      findings.
AB  - Pneumatosis Intestinalis is defined as the infiltration of gas into the bowel
      wall. It is a radiological and intra-operative finding of varying aetiology which
      varies from benign to life threatening conditions. We describe here a case of a
      67 year old woman who presented with diffuse abdominal pain and was found to have
      Pneumatosis Intestinalis. 

PMID- 24946172
TI  - Papillary thyroid carcinoma presenting as an asymptomatic pelvic bone metastases.
AB  - Thyroid carcinoma is rare comprising 1% of all malignancies and commonly presents
      as a neck lump. Papillary thyroid carcinoma unlike follicular thyroid carcinoma
      tends not to metastasise to distant sites. We present a case of papillary thyroid
      carcinoma presenting as a solitary asymptomatic pelvic bone metastases and
      highlight current management of bone metastases. A 59-year old female was found
      on abdominal computerised tomography to have an incidental finding of a 4.5 cm
      soft tissue mass in the right iliac bone. Biopsy of the lesion confirmed
      metastatic thyroid carcinoma. There was no history of a neck lump, head and neck
      examination was normal. Further imaging confirmed focal activity in the right
      lobe of the thyroid. A total thyroidectomy and level VI neck dissection was
      performed and histology confirmed follicular variant of papillary carcinoma.
      Early detection of bone metastases have been shown to improve prognosis and
      thyroid carcinoma should be considered as a potential primary malignancy. 

PMID- 24946170
TI  - Pancreatic fistulae after a pancreatico-duodenectomy: are pancreatico
      gastrostomies safer than pancreatico-jejunostomies? An expertise-based trial and
      propensity-score adjusted analysis.
AB  - BACKGROUND: A pancreatic fistula (PF) is a major contributor to morbidity and
      mortality after a pancreaticoduodenectomy (PD). There remains debate as to
      whether re-establishing pancreaticoenteric continuity by a pancreatico
      gastrostomy (PG) can decrease the risk of a PF and complications compared with a
      pancreatico-jejunostomy (PJ). The outcomes of patients undergoing these
      reconstructions after a PD were compared. METHOD: Patients undergoing a PD
      between 1999 and 2011 were selected from a prospective database and having
      undergone either a PG or PJ reconstruction. A propensity-score adjusted
      multivariate logistic regression was performed to identify the effect of surgical
      technique on outcomes of PF, delayed gastric emptying (DGE) and total
      complications. RESULTS: Twenty-three out of 103 and 20 out of 103 (P = 0.49)
      patients had PF and 74 out of 103 and 55 out of 103 patients had all-grades DGE
      in the PG and PJ groups, respectively (P = 0.02). The groups did not differ with
      regards to Clavien-Dindo grade of complications (P = 0.29) but did differ with
      regards to the Comprehensive Complication Index (CCI) (38.4 versus 31.4 for PG
      versus PG, respectively, P = 0.02.) Propensity-score adjusted multivariate
      analysis showed no effect of PG on PF (P = 0.89), DGE grades B/C (P = 0.9) or CCI
      (P = 0.41). There remained an effect on all-grades of DGE (P = 0.012.)
      DISCUSSION: Patients undergoing PG reconstruction had a similar rate of PF as
      those undergoing a PJ after a PD.

PMID- 24946174
TI  - Transhepatic perforation of the gallbladder: rare complication of a common
      disease.
AB  - Acute cholecystitis leading to gallbladder perforation is relatively common.
      However, transhepatic perforation of the gallbladder leading to biliary
      peritonitis is very rare. We present a rare case of biliary peritonitis caused by
      transhepatic perforation of the gallbladder. 

PMID- 24946175
TI  - External iliac vein compression and thrombosis by a migrated acetabular screw
      following total hip arthroplasty.
AB  - A fifty-nine year old gentleman underwent a right total hip replacement in
      another hospital for protrusio osteoarthritis of the right hip. Post-operatively
      he developed a large right-sided ilio-femoral deep venous thrombosis. A pelvic
      radiograph showed that the acetabular construct had migrated medially into the
      pelvis with a CT scan showing compression of the external iliac vessels by one of
      the acetabular screws. Revision surgery was carried out in collaboration with the
      vascular surgeons. This case report highlights the importance of pre-operative
      planning to avoid medial wall perforation in patients with protrusio
      osteoarthritis. It also illustrates an unusual complication of compression of the
      external iliac vessels causing massive ilio-femoral thrombosis. The management of
      this potentially limb threatening complication is described in this case report. 

PMID- 24946176
TI  - Idiopathic cervical osteomyelitis presenting as dysphagia.
AB  - We discuss a case of idiopathic cervical epidural abscess, complicated by
      osteomyelitis, presenting with dysphagia as the main complaint. No predisposing
      factors were identified and blood cultures were negative. Case was treated
      conservatively by long course of IV antibiotics. We present a review of
      presentation of spinal epidural abscesses and indications for surgical
      intervention. 

PMID- 24946178
TI  - Meta-analysis.

PMID- 24946177
TI  - Relative exposure to controller therapy and asthma exacerbations: a validation
      study in community pharmacies.
AB  - PURPOSE: "Controllers-to-total asthma drug" ratios computed from claims data
      identify asthmatics at risk of exacerbations. Direct link of ratios to data
      obtained from patients, such as control and recent outcomes, would facilitate
      their interpretation. We studied the relationship between R1 ratio (inhaled
      corticosteroids (ICS)/total anti-asthma drug ratio) and the Asthma Control Test.
      Comparisons were also conducted for secondary outcomes (asthma-related hospital
      contacts, monthly medical contacts, use of oral corticosteroids, and perception
      of disease burden). Results with R1 ratio were compared with those obtained with
      a second ratio, "ICS-plus-leukotriene receptor antagonist/total asthma drug" (R2
      = ICS + leukotriene receptor antagonist/total anti-asthma drugs). METHODS: A
      survey was conducted in community pharmacies. Patients visiting with a
      prescription of anti-asthma drug and >=12 months of drug dispensing recorded in
      the pharmacy were consecutively recruited. Dispensing data were linked to patient
      reported outcomes. Asthma control and secondary outcomes were compared for both
      ratios between low-controller-ratio (R < 50%) and high-controller-ratio groups (R
      >= 50%), after excluding null values. RESULTS: Of the 919 eligible patients (mean
      age 37 years, 55% women), 90.2% and 92.4% had non-null values for R1 and R2,
      respectively. Compared with the low-controller-ratio groups, adjusted risks of
      being uncontrolled were significantly lower in the high-controller-ratio groups
      (RR = 0.64, 95%CI [0.54, 0.77] and RR = 0.57, 95%CI [0.47, 0.70], for R1 and R2
      ratios, respectively). Likewise, fewer patients with secondary outcomes were
      observed in the high-controller-ratio groups, for both ratios. CONCLUSION: Asthma
      was better controlled among patients with high controller ratios, along with
      fewer asthma-related outcomes, for both R1 and R2 ratios. This confirms the
      utility of asthma/drug ratios in identifying patients at risk of exacerbations,
      notably in claims data.

PMID- 24946179
TI  - An estimate of the prevalence of COPD in Africa: a systematic analysis.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is among the leading
      causes of death globally, accounting for about 3 million deaths worldwide in
      2011. We aimed to estimate the prevalence of COPD in Africa in the year 2010 to
      provide the information that could assist health policy in the region. METHODS:
      We conducted a systematic review of Medline, EMBASE and Global Health for studies
      on COPD published between 1990 and 2012. We included original population based
      studies providing estimates of the prevalence of COPD. We considered the reported
      estimates in terms of the mean age of the sample, sex ratio, the year of study
      and the country of the study as possible covariates. RESULTS from two different
      types of studies, i.e., based on spirometric and non-spirometric diagnosis of
      COPD, were further compared. The United Nation Population Division's population
      figures were used to estimate the number of COPD cases in the year 2010. RESULTS:
      Our search returned 243 studies, from which only 13 met our selection criteria
      and only five were based on spirometry. The difference in the median prevalence
      of COPD in persons aged 40 years or older based on spirometry data (13.4%; IQR:
      9.4%-22.1%) and non-spirometry data (4.0%; IQR: 2.1%-8.9%) was statistically
      significant (p = 0.001). There was no significant effect of the gender or the
      year of the study on the reported prevalence of COPD in either set of studies.
      The prevalence of COPD increased with age in spirometry-based studies (p =
      0.017), which is a plausible finding suggesting internal consistency of
      spirometry-based estimates, while this trend was not observed in studies using
      other case definitions. When applied to the appropriate age group (40 years or
      more), which accounted for 196.4 million people in Africa in 2010, the estimated
      prevalence translates into 26.3 million (18.5-43.4 million) cases of COPD.
      Comparable figures for the year 2000 based on the same prevalence rates would
      amount to 20.0 million (14.1-33.1), suggesting an increase of 31.5% over a decade
      that is attributable to ageing of the African population alone. CONCLUSION: Our
      findings suggest that COPD is likely to already represent a very large public
      health problem in Africa. Moreover, rapidly ageing African population should
      expect a steady increase in the number of COPD cases in the next decade and
      beyond. The quantity and quality of available evidence does not match the size of
      the problem. There is a need for more research on COPD prevalence, but also
      incidence, mortality and risk factors in Africa. We hope this study will raise
      awareness of COPD in Africa and encourage further research.

PMID- 24946180
TI  - De novo synthesis of brominated dioxins and furans.
AB  - On the basis of laboratory experiments with model mixtures (active carbon+CuBr2
      at different loads), this work studies the formation of polybrominated dibenzo-p
      dioxins and dibenzofurans (PBDD/Fs) by de novo synthesis. For the different
      samples, the temperature of the maximum carbon oxidation rate was determined by
      thermogravimetric analysis, and a kinetic model was proposed for the degradation
      of the materials in an oxidizing atmosphere (synthetic air). The effect of the
      addition of different amounts of CuBr2 was studied, finding that its presence
      accelerates the degradation of the carbonaceous structure in the presence of
      oxygen. The thermal degradation of the samples in air is satisfactorily described
      by a first-order single-reaction model. In addition, combustion runs of one of
      the mixtures (consisting of activated carbon+50 wt % CuBr2, pyrolyzed at 700 
      degrees C) were performed in a quartz horizontal laboratory furnace. The analysis
      of the emissions and the solid residue proved the formation of brominated dioxins
      and furans at 300, 400, and 500  degrees C, with a maximum yield at 300  degrees
      C (91.7 ng/g of total PBDD/Fs) and a higher bromination degree with increasing
      temperature.

PMID- 24946181
TI  - AMPK-alpha1 functions downstream of oxidative stress to mediate neuronal atrophy
      in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurological disorder that is
      induced by a CAG trinucleotide expansion in exon 1 of the Huntingtin (HTT) gene.
      We previously reported that the abnormal activation of an important energy
      sensor, AMP-activated protein kinase alpha1 (AMPK-alpha1), occurs in the brains
      of mice and patients with HD, which suggests that this abnormal activation may
      contribute to neuronal degeneration in HD. In the present study, we demonstrated
      that the elevated oxidative stress that was evoked by a polyQ-expanded mutant HTT
      (mHTT) caused the abnormal activation of AMPK-alpha1 and, subsequently, resulted
      in neurotoxicity in a striatal progenitor cell line (STHdh(Q109)) and in the
      striatum of a transgenic mouse model of HD (R6/2). The systematic administration
      of an antioxidant (N-acetyl-cysteine, NAC) to R6/2 mice suppressed the activation
      of AMPK-alpha1, reduced neuronal toxicity, which was assessed by the activation
      of caspases, increased neuronal density, ameliorated ventricle enlargement, and
      improved motor dysfunction. This beneficial effect of NAC in vivo appears to be
      direct because NAC also reduced the activation of AMPK-alpha1 and the death of
      STHdh(Q109) cells upon elevated oxidative stress. Moreover, the activation of
      AMPK enhanced the level of oxidative stress in STHdh(Q109) cells, in primary
      neurons of R6/2 mice, and in the striatum of two different HD mouse models (R6/2
      and Hdh(150Q/+)), whereas the inhibition of AMPK reduced the level of oxidative
      stress. Collectively, our findings suggest that positive feedback regulation
      between the elevated oxidative stress and the activation of AMPK-alpha1
      contributes to the progression of HD. 

PMID- 24946182
TI  - Mitochondrial bioenergetics deregulation caused by long-chain 3-hydroxy fatty
      acids accumulating in LCHAD and MTP deficiencies in rat brain: a possible role of
      mPTP opening as a pathomechanism in these disorders?
AB  - Long-chain 3-hydroxylated fatty acids (LCHFA) accumulate in long-chain 3-hydroxy
      acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP)
      deficiencies. Affected patients usually present severe neonatal symptoms
      involving cardiac and hepatic functions, although long-term neurological
      abnormalities are also commonly observed. Since the underlying mechanisms of
      brain damage are practically unknown and have not been properly investigated, we
      studied the effects of LCHFA on important parameters of mitochondrial homeostasis
      in isolated mitochondria from cerebral cortex of developing rats. 3
      Hydroxytetradecanoic acid (3 HTA) reduced mitochondrial membrane potential,
      NAD(P)H levels, Ca(2+) retention capacity and ATP content, besides inducing
      swelling, cytochrome c release and H2O2 production in Ca(2+)-loaded mitochondrial
      preparations. We also found that cyclosporine A plus ADP, as well as ruthenium
      red, a Ca(2+) uptake blocker, prevented these effects, suggesting the involvement
      of the mitochondrial permeability transition pore (mPTP) and an important role
      for Ca(2+), respectively. 3-Hydroxydodecanoic and 3-hydroxypalmitic acids, that
      also accumulate in LCHAD and MTP deficiencies, similarly induced mitochondrial
      swelling and decreased ATP content, but to a variable degree pending on the size
      of their carbon chain. It is proposed that mPTP opening induced by LCHFA disrupts
      brain bioenergetics and may contribute at least partly to explain the neurologic
      dysfunction observed in patients affected by LCHAD and MTP deficiencies. 

PMID- 24946183
TI  - Bisphosphonates and connexin 43: a critical review of evidence.
AB  - Bisphosphonates (BPs) are drugs commonly used in the treatment of various disease
      arising or affecting bone tissue. There is a standard use in bone neoplasia and
      metastasis, hormonal and developmental disorders as well as for compensation of
      adverse effects in several medical therapies. Many in-vivo and in-vitro studies
      have assessed the efficacy of this drug and its function in cellular scale. In
      this concern, BPs are described to inhibit the resorptive function of osteoclasts
      and to prevent apoptosis of osteoblasts and osteocytes. They can preserve the
      osteocytic network, reduce fracture rate, and increase the bone mineral content,
      which is therapeutically used. Connexin 43 (Cx43) is a crucial molecule for basal
      regulation of bone homeostasis, development, and differentiation. It is described
      for signal transduction in many physiological and pathological stimuli and
      recently to be involved in BP action.

PMID- 24946184
TI  - Severe pulmonary arterial hypertension secondary to lupus in the emergency
      department: proactive intense care associated with a better short-term survival.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of
      systemic lupus erythematosus (SLE) and could be an acute critical condition
      presenting to the emergency department (ED). Our previous retrospective study
      revealed that the ED-related mortality of such patients was over 50%. The aim of
      the current prospective study is to initiate a proactive intense care strategy on
      severe SLE-PAH patients in the emergency setting and evaluate its impact on the
      short-term survival. METHODS: The proactive intense care strategy was applied,
      which includes: (i) an education and training course on the topic of SLE-PAH for
      ED physicians; (ii) a SLE-PAH patient triage protocol with prompt specialist
      consultation and admission; and (iii) intensive care with prompt initiation of
      combination PAH-targeted therapy, that is, at least two drugs from the three
      categories as represented by iloprost, bosentan and sildenafil. Consecutive SLE
      PAH patients with WHO functional class III or IV who attended the ED were
      enrolled following the aforementioned protocol. A historical group of SLE-PAH
      patients in the ED (n = 11) was set up as a comparison, and 3-month short-term
      survival was calculated. RESULTS: During October 2010 to December 2012, a total
      of 11 consecutive severe SLE-PAH patients were included in the present study.
      Compared with the historical group, an improved short-term survival can be
      appreciated over time (historical group vs. proactive group, 27.3% vs. 72.7%, P =
      0.033). The application of PAH-targeted combination therapy apparently
      contributed to the better outcome (P = 0.0099). CONCLUSIONS: Proactive care and
      combination PAH-targeted treatment can improve short-term survival of severe SLE
      PAH in the emergency setting.

PMID- 24946185
TI  - An optimized DNA extraction protocol for benthic Didymosphenia geminata.
AB  - Didymosphenia geminata mats display few cells in relation to extracellular
      material and contain polysaccharides and heavy metals that interfere with
      molecular studies. We describe an optimized DNA extraction protocol that help to
      overcome these difficulties. Our protocol outperformed five previously described
      DNA extraction techniques. 

PMID- 24946187
TI  - Editorial.

PMID- 24946188
TI  - Drug treatments for schizophrenia - past, present and future.
AB  - The typical antipsychotic drugs, which have been the mainstay of treatment for
      schizophrenia for many years, are potent antagonists of D2 receptors. However,
      their lack of selectivity for D2 receptors in the mesolimbic areas compared with
      the nigrostriatal areas of the brain has resulted in an association at
      therapeutic doses with extrapyramidal side-effects, an increased risk for tardive
      dyskinesia and increased prolactin levels. Together with other significant side
      effects, this profile has limited their acceptability for antipsychotic
      treatment, resulting in poor compliance, increased risk of relapse and increased
      severity of disease. A new generation of antipsychotics, the 'atypicals', which
      show greater selectivity for mesolimbic D2 receptors combined with effects on 5
      HT2 receptors, have demonstrated antipsychotic efficacy, with a significantly
      lower incidence of extrapyramidal effects than seen with haloperidol, and often
      at placebo level. The first atypical antipsychotic, clozapine, has been
      restricted to use in treatment-resistant schizophrenia because of an association
      with agranwlocytosis. Two other drugs are now available, olanzapine and
      sertindole, and two others, quetiapine and ziprasidone, are in late-stage
      development. The profile of these drugs is reviewed, together with future
      treatment possibilities. 

PMID- 24946189
TI  - Quetiapine ('Seroquel'); an effective and well-tolerated atypical antipsychotic.
AB  - Antipsychotic drugs are the mainstay of treatment of patients with schizophrenia.
      These drugs cause many side-effects, of which the most problematic are
      extrapyramidal symptoms. This paper reviews published preclinical and clinical
      studies on quetiapine, a new atypical antipsychotic. The preclinical studies
      predict a low risk of extrapyramidal symptoms, and this is borne out in clinical
      trials in patients with relapses of moderate or severe schizophrenia. Indeed, the
      occurrence of extrapyramidal symptoms with quetiapine is indistinguishable from
      that with placebo across the dose range. In general, quetiapine is well
      tolerated, producing side-effects no worse than those encountered with standard
      antipsychotics. With regard to efficacy, quetiapine appears as effective as the
      older antipsychotics haloperidol and chlorpromazine in treating schizophrenia.
      Quetiapine thus offers the clinician a significant advance over standard
      antipsychotic drugs. 

PMID- 24946186
TI  - Characterization of human plasma proteome dynamics using deuterium oxide.
AB  - PURPOSE: High-throughput quantification of human protein turnover via in vivo
      administration of deuterium oxide ((2) H2 O) is a powerful new approach to
      examine potential disease mechanisms. Its immediate clinical translation is
      contingent upon characterizations of the safety and hemodynamic effects of in
      vivo administration of (2) H2 O to human subjects. EXPERIMENTAL DESIGN: We
      recruited ten healthy human subjects with a broad demographic variety to evaluate
      the safety, feasibility, efficacy, and reproducibility of (2) H2 O intake for
      studying protein dynamics. We designed a protocol where each subject orally
      consumed weight-adjusted doses of 70% (2) H2 O daily for 14 days to enrich body
      water and proteins with deuterium. Plasma proteome dynamics was measured using a
      high-resolution MS method we recently developed. RESULTS: This protocol was
      successfully applied in ten human subjects to characterize the endogenous
      turnover rates of 542 human plasma proteins, the largest such human dataset to
      date. Throughout the study, we did not detect physiological effects or signs of
      discomfort from (2) H2 O consumption. CONCLUSIONS AND CLINICAL RELEVANCE: Our
      investigation supports the utility of a (2) H2 O intake protocol that is safe,
      accessible, and effective for clinical investigations of large-scale human
      protein turnover dynamics. This workflow shows promising clinical translational
      value for examining plasma protein dynamics in human diseases.

PMID- 24946190
TI  - Serotonin re-uptake inhibitors in the treatment of premenstrual dysphoria:
      Current state of knowledge.
AB  - Late luteal phase dysphoric disorder (LLPDD) and the more recently introduced
      premenstrual dysphoric disorder (PMDD) are recognized psychiatric disorders that
      consist of distressing emotional and behavioural symptoms that occur
      premenstrually. Recently, advances have been made in understanding the aetiology
      of the disorder, with clear evidence to implicate the serotonergic system. In
      women with predominately psychological symptoms, selective serotonin re-uptake
      inhibitors (SSRIs), as well as clomipramine, have demonstrated excellent efficacy
      and minimal side effects. 

PMID- 24946191
TI  - Attention Deficit Hyperactivity Disorder (ADHD): Selected review of causes,
      comorbidity and treatment.
AB  - A limited review of the causes, comorbidity, diagnosis and treatment is offered
      to emphasize the difficulties in diagnosing and treating Attention Deficit
      Hyperactivity Disorder and Hyperkinetic Disorder. Some of the difficulties
      include controversies about the existence of a separate disorder, the changes in
      symptoms with age, the short-lived improvement on medication and the claims of
      unsubstantiated treatments. This selected review should help the reader to
      consider recent findings in the aetiology, diagnosis and treatment of ADHD. 

PMID- 24946192
TI  - Clozapine response in early treatment-resistant schizophrenia.
AB  - Eleven consecutive schizophrenic patients with a mean duration of illness of 2.2
      (range 0.9-3.8) years and early signs of resistance to conventional neuroleptics
      were studied prospectively in a 26-week open trial with clozapine (mean dose
      192.5 mg at week 8 and 225.0 mg at end-point). Of the ten patients who completed
      the study, nine improved by 20% or more on total Brief Psychiatric Rating Scale
      (BPRS) scores; six (good responders) showed more than 30%, and four (fair
      responders) 21-26% improvement on total Positive and Negative Syndrome Scale
      (PANSS) scores. The improvement was observed mainly within the first 8 weeks.
      Duration of illness correlated negatively (P=0.047) with the decrease of positive
      PANSS scores. The duration of illness of the fair responders was more than twice
      that of the good responders. Clozapine appears to be a safe and effective
      treatment alternative for early treatment-resistant schizophrenic patients. These
      patients seem to respond to relatively low clozapine doses. Early rather than
      late transfer to clozapine in this population may be of benefit for later
      clinical outcome. 

PMID- 24946193
TI  - Management of resistant depression.
AB  - The inadequate assessment and management of depression can lead to the erroneous
      diagnosis of treatment resistance. After briefly considering the definition and
      diagnosis of resistant depression, the authors describe the principles and
      methods of antidepressant therapy, emphasizing the systematic use of medication
      and the importance of therapeutic drug monitoring. The application of these is
      then discussed in a clinical context, and illustrated with examples. 

PMID- 24946194
TI  - Do SSRIs prolong seizure duration during ECT?
AB  - The effect of selective serotonin re-uptake inhibitors (SSRIs) on seizure
      duration during a course of electroconvulsive therapy (ECT) was evaluated in a
      retrospective study. Although numbers in the SSRI group were small (n=13), there
      was a significantly longer seizure duration with SSRIs, compared with tricyclic
      antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). More studies are
      needed to see whether this is a general finding or whether it reflects individual
      variation, and most importantly, what effects, if any, this has on clinical
      outcome. 

PMID- 24946195
TI  - Effects of trazodone on insomnia and anxiety in depressed patients: a clinical
      and sleep EEG study.
AB  - Clinical and sleep EEG effects of trazodone in major depression were investigated
      using a 5-week single-blind study design. Nine patients with DSM-N major
      depression were selected. Trazodone (50-250 mg) was given following a 2-week
      placebo run-in period. Both sleep and psychiatric evaluations were performed at
      different time points. Early and persistent sleep-inducing effects were detected,
      including the improvement of objective insomnia features and increased amounts of
      slow wave sleep. However, no significant changes of REM sleep measures were
      found. The sleep EEG changes seem to be related to the clinical improvement of
      both anxiety and insomnia, but there is no apparent relationship with the
      antidepressant action, which occurs at a later stage of the treatment. Trazodone
      may be useful in depressed patients, either as a hypnotic-like agent or as an
      effective antidepressant drug with beneficial effects on sleep. 

PMID- 24946196
TI  - Changing pattern of drug use in individuals with severe drug dependence following
      inpatient treatment.
AB  - Ninety-seven subjects (92 of whom were opiate users) admitted to an inpatient
      treatment unit were followed 3, 6, 9, and 12 months after discharge using the
      Substance Abuse Assessment Questionnaire (SAAQ).(1) The subjects presented
      problems of severe drug use, frequently complicated by additional difficulties;
      67% of the sample completed detoxification. Significant reductions in daily drug
      use were seen at 12 months for each major class of drug, except cannabis. One
      third of daily opiate users had been abstinent from opiates for at least one
      month prior to the final follow-up. Most changes took place between admission and
      the 3-month follow-up, and these improvements were maintained across the sample
      as a whole. Within the sample, fluctuations in drug use were observed, with
      subjects both relapsing to, and remitting from, drug use. Subjects who achieved
      at least one 3-month period of abstinence were more likely to have been employed
      at admission, and also more likely to have committed an offence immediately prior
      to admission, than those who did not achieve this level of abstinence. These
      results suggest that detoxification programmes produce benefits which can be
      maintained in the medium term. Further longitudinal studies are required to
      investigate the triggers for both relapse and remission. 

PMID- 24946197
TI  - Koro in a Caucasian male with panic disorder.
AB  - A case of koro in a white English male is described. This is followed by a brief
      review of other similar cases and possible psychophysiological mechanisms. 

PMID- 24946199
TI  - Development and feasibility of a child obesity prevention intervention in general
      practice: the Healthy 4 Life pilot study.
AB  - AIM: Approximately 20% of Australian pre-school children are overweight. Primary
      care providers have a crucial role in identifying children at risk of unhealthy
      weight gain and to offer advice and suggestions to parents. The Healthy 4 Life
      pilot study aimed to develop and test the feasibility of a practice nurse (PN)
      led brief intervention into a healthy kid's check in general practice. METHODS: A
      PN intervention was developed based on a needs assessment and existing
      literature. A workshop was conducted, and resources were provided to enable four
      PNs to deliver a brief obesity prevention intervention to parents. Nurses then
      incorporated the Healthy 4 Life components into the healthy kid's checks they
      conducted on the next 10 children. Medical records were reviewed and nurses
      interviewed to establish the feasibility of the intervention. RESULTS: All of the
      nurses incorporated some Healthy 4 Life components into their healthy kid's
      checks. Body mass index was calculated and plotted for all children, and advice
      around healthy eating was offered in 60% of consultations; however, advice about
      limiting screen time provided in only 2% of consultations. Nurses reported that
      the intervention fitted well with their current practice, although time
      constraints were a concern for some nurses and some parents. CONCLUSION: The
      provision of a brief training workshop and resources can equip nurses in general
      practice to offer an obesity prevention intervention to parents of young
      children. Further research is required to examine the impact of such an
      intervention on parent and child behaviours and the sustainability of such
      practices for PNs.

PMID- 24946200
TI  - Organocatalytic ring-opening polymerization of morpholinones: new strategies to
      functionalized polyesters.
AB  - The oxidative lactonization of N-substituted diethanolamines with the Pd catalyst
      [LPd(OAc)]2(2+)[OTf(-)]2 generates N-substituted morpholin-2-ones. The
      organocatalytic ring-opening polymerization of N-acyl morpholin-2-ones occurs
      readily to generate functionalized poly(aminoesters) with N-acylated amines in
      the polyester backbone. The thermodynamics of the ring-opening polymerization
      depends sensitively on the hybridization of the nitrogen of the heterocyclic
      lactone. N-Acyl morpholin-2-ones polymerize readily to generate
      polymorpholinones, but the N-aryl or N-alkyl substituted morpholin-2-ones do not
      polymerize. Experimental and theoretical studies reveal that the thermodynamics
      of ring opening correlates to the degree of pyramidalization of the endocyclic N
      atom. Deprotection of the poly(N-Boc-morpholin-2-one) yields a water-soluble,
      cationic polymorpholinone. 

PMID- 24946203
TI  - Demographic characteristics of MS patients in Poland's upper Silesia region.
AB  - OBJECTIVES: In Poland, no national registry of MS patients has yet been
      introduced. So far, no demographic studies have been conducted in patients with
      MS in Upper Silesia. The aim of the present study was to evaluate, for the first
      time, a selected demographic and clinical parameters in MS patients from the
      Upper Silesia region and compare these characteristics with previously published
      data from other regions of Poland. MATERIALS & METHODS: 640 patients with
      clinically defined MS, were prospectively and randomly selected for the study.
      Social, socio-economic, and demographic data were obtained through a
      questionnaire study. All subjects performed a self-assessment of their health
      condition using EQ-5D and EQ-VAS version questionnaires. RESULTS: The ratio of
      women to men was 2.18. The average age of onset was 29.6 +/- 11.1 years; the
      disease duration was 7.9 +/- 4.5 years. The relapsing-remitting form of MS was
      diagnosed in 73.12%. In 71.25% the onset was monofocal and in 28.75% multifocal
      disease onset was observed. Among the studied population 339 (52.97%) patients
      were still employed. A mean EQ-VAS score of 66.11 +/- 20.12 was calculated.
      CONCLUSIONS: Results from our study identify for the first time the demographic
      and clinical characteristics of the Upper Silesia MS population.

PMID- 24946201
TI  - Active inhibition of task-irrelevant sounds and its neural basis in patients with
      attention deficits after traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To examine active inhibition of irrelevant stimuli and
      evaluate its neural basis using functional near infrared spectroscopy in patients
      with attention deficits after traumatic brain injury (TBI). RESEARCH DESIGN: Case
      control study. METHODS AND PROCEDURES: Ten patients with TBI and 10 healthy
      control subjects participated in this study. The Paced Auditory Serial Addition
      Test (PASAT) was performed with (distracting PASAT) and without (PASAT)
      distracting Japanese kana phonetic characters presented between each number. A
      block design was used. Subjects alternately performed each task three times. MAIN
      OUTCOMES AND RESULTS: Healthy controls performed better than patients with TBI on
      both the tasks. When performing the PASAT, healthy controls showed significant
      activity in every region of interest except the right lateral prefrontal cortex
      (PFC), but patients with TBI showed significant activity only in the left
      anterior PFC and left lateral PFC. When performing the distracting PASAT, the
      right lateral PFC was active in healthy controls, but not in patients with TBI.
      CONCLUSION: These results confirm that patients with moderate-to-severe TBI were
      affected by distractors that influenced order processing. It is suggested that
      the working memory of patients with TBI was affected by distracting stimuli,
      whereas that of healthy individuals was not.

PMID- 24946204
TI  - Neurogenin 2 enhances the neuronal differentiation of skin-derived precursors.
AB  - Skin-derived precursors (SKPs), a novel stem cell population isolated from
      mammalian skin, can differentiate into neural and mesodermal lineages. Cell
      therapy using SKPs seems like a promising approach for the treatment of neural
      diseases, however, the low efficiency of neuronal differentiation limited their
      clinical application. In the present study, we transfected neurogenin 2 (Ngn2), a
      member of the bHLH transcription factor family, into SKPs by lentivirus.
      Morphological analysis, immunocytochemistry, Western blot, and
      electrophysiological analysis were performed to identify the cells derived from
      SKPs following 7-14 d neural induction. The results of immunocytochemistry
      staining showed that expression of neuronal markers, including MAP2, NF and NeuN
      were significantly elevated compared with those in GFP-SKPs and parental SKPs.
      Western blot confirmed the increased expression of NF-M and NeuN in Ngn2-SKPs
      derived cells. Moreover, electrophysiological analysis showed that Ngn2-SKPs
      derived neurons also acquired voltage-gated Na+ channels, which were absent in
      GFP-SKPs. Furthermore, western blot showed that Ngn2 enhanced the expression of
      Delta-like1, which reduced the level of Hes1 and suppressed Notch pathway.
      Therefore, overexpression of Ngn2 enhanced the neural differentiation of SKPs,
      probably through cis-inhibiting of Notch signal pathway. 

PMID- 24946205
TI  - Identification of disease-related miRNAs based on co-expression network in spinal
      cord injury.
AB  - OBJECTIVE: This study aimed to construct miRNA co-expression network by using
      miRNA microarray data and screen the miRNAs associated with spinal cord injury
      (SCI) by comparative analysis, which might be considered as molecule labels for
      future forecasts or therapies. METHODS: We first downloaded SCI gene expression
      data GSE19890 from GEO (Gene Expression Omnibus), then constructed the miRNA co
      expression network under three different states and analyzed the topologic
      attributes of network. After that, miRNAs associated with SCI were screened and
      subjected to function analysis by DAVID (Database for Annotation, Visualization
      and Integrated Discovery). RESULTS: In the co-expression network, miR-520a and
      miR-193b had the largest degree in the SCI and sham groups, respectively. A total
      of 22 differentially expressed miRNAs were identified. MiR-32 and miR-471 were
      the most significantly expressed in the SCI group compared with control and sham
      groups, respectively, which were newly reported to be related to SCI in this
      study. Function enrichment analysis of the target genes indicated that the
      screened miRNA were associated with cell adhesion, cytoplasmic vesicle and so on.
      CONCLUSIONS: MiRNAs identified in this study could be considered targets for SCI
      diagnosis and therapy.

PMID- 24946207
TI  - Increasing the Width of Keratinized Mucosa in Maxillary Implant Areas Using a
      Split Palatal Bridge Flap: Surgical Technique and 1-Year Follow-Up.
AB  - Sufficient soft-tissue coverage of maxillary implant sites may be difficult to
      achieve, especially after bone augmentation. The use of vestibular flaps moves
      keratinized mucosa (KM) toward the palate and may be disadvantageous for future
      peri-implant tissue stability. This study describes a new split palatal bridge
      flap (SPBF) that achieves tension-free wound closure and increases the KM width
      in maxillary implant areas. We began SPBF surgery with a horizontal incision in
      the palatal soft tissue to create a split-thickness flap. The second incision was
      performed perpendicular to the first, using a bridge design, at a distance of 10
      to 15 mm. The superior layer can be moved crestally and sutured to cover the soft
      tissue defect. The defect width was measured using a periodontal probe. The
      inferior layer was left exposed, and secondary wound healing created new KM in
      this region. This SPBF technique was performed on 37 patients. Of these, 16
      patients were included in the assessment of clinical peri-implant outcomes. All
      of the SPBF procedures successfully resulted in a palatal regeneration of KM
      through secondary wound healing (mean regeneration width, 4.51 +/- 1.17 mm;
      range, 3-6 mm). The 1-year follow-up of 16 patients revealed a mean pocket
      probing depth of 3.22 +/- 0.6 mm with zero cases of peri-implantitis. The
      vestibular KM width at the involved implants was 2.82 +/- 1.07 mm (range, 1.5-6
      mm). Surgery for SPBF may be a promising technique for covering soft-tissue
      defects and increasing KM width in maxillary implant surgery. 

PMID- 24946208
TI  - Balancing energetic and cognitive resources: memory use during search depends on
      the orienting effector.
AB  - Search outside the laboratory involves tradeoffs among a variety of internal and
      external exploratory processes. Here we examine the conditions under which item
      specific memory from prior exposures to a search array is used to guide attention
      during search. We extend the hypothesis that memory use increases as perceptual
      search becomes more difficult by turning to an ecologically important type of
      search difficulty - energetic cost. Using optical motion tracking, we introduce a
      novel head-contingent display system, which enables the direct comparison of
      search using head movements and search using eye movements. Consistent with the
      increased energetic cost of turning the head to orient attention, we discover
      greater use of memory in head-contingent versus eye-contingent search, as
      reflected in both timing and orienting metrics. Our results extend theories of
      memory use in search to encompass embodied factors, and highlight the importance
      of accounting for the costs and constraints of the specific motor groups used in
      a given task when evaluating cognitive effects. 

PMID- 24946209
TI  - Alteration of copper-zinc superoxide dismutase 1 expression by influenza A virus
      is correlated with virus replication.
AB  - Viruses have evolved mechanisms designated to potentiate virus replication by
      modulating the physiological condition of host cells. The generation of reactive
      oxygen species (ROS) during infection with influenza virus A (IAV) is a well
      established mechanism in animals, but little is known about the generation of ROS
      in in vitro cell culture models and about its role in virus replication. We show
      here that IAV H1N1 infected human alveolar cells increased superoxide anion level
      mainly by suppressing the copper-zinc superoxide dismutase 1 (SOD1) gene, and
      that the SOD1-controlled generation of ROS was tightly correlated with virus
      replication. The transcription factor Sp1, which is a major element of the
      proximal region of the sod1 promoter, was slightly downregulated at the
      transcriptional level during IAV infection, and subsequently modulated by post
      translational control. A gradual reduction of whole Sp1 was largely responsible
      for the repression of sod1 transcription with increasing time post-infection, and
      their rescue by the proteasome inhibitor, MG132, proved the involvement of
      proteasomal degradation in Sp1 regulation during IAV infection. Furthermore, we
      observed that expression of viral polymerase PB1 was inversely proportional to
      SOD1 level. The antioxidant N-acetyl-cysteine (NAC) neutralized IAV-mediated
      oxidative stress, and either NAC treatment or sod1 transfection considerably
      diminished viral polymerase activity. These data indicate that IAV-induced SOD1
      repression, which may cause impaired redox balance in host cells, can be
      attributed, at least in part, to enhance viral replication. 

PMID- 24946210
TI  - 3-Hydroxy-3',4'-dimethoxyflavone suppresses Bcl-w-induced invasive potentials and
      stemness in glioblastoma multiforme.
AB  - 3-Hydroxy-3',4'-dimethoxyflavone (HDMF) is a natural chemical product that is not
      currently regarded as a drug. In our study, we employed glioblastoma cells and
      cell biology and biochemistry approaches to investigate the potential of HDMF as
      a natural anticancer therapy option. FACS analysis showed that treatment
      concentration of HDMF does not exert cytotoxicity on U251 cells. Wound-healing
      and invasion assays showed that HDMF dose-dependently decreased the migratory and
      invasive potentials of these cells, likely by indirectly inhibiting MMP-3
      activity as a result of the inhibition of p38 and ERK signaling proteins - an
      effect of HDMF also shown by Western blotting. HDMF inhibits Bcl-w-induced
      neurosphere formation and the expression of glioma stem cell markers, such as
      Musashi, Sox-2 and c-myc. These results indicate that HDMF suppresses migratory
      or invasive potentials and stemness and functions as a negative agent against the
      aggressiveness of glioblastoma cells. We propose that HDMF has potential as
      anticancer drug for inhibiting the aggressiveness of glioblastoma multiforme
      (GBM). 

PMID- 24946211
TI  - Mitochondrial protein cyclophilin-D-mediated programmed necrosis attributes to
      berberine-induced cytotoxicity in cultured prostate cancer cells.
AB  - The prostate cancer is one of the leading causes of men's cancer mortality. The
      development of alternative chemotherapeutic strategies is urgent. Berberine has
      displayed significant anti-prostate cancer activities. The underlying mechanisms
      are not fully understood. In the current study, we found that berberine induced
      apoptosis and programmed necrosis in cultured prostate cancer cells (LNCaP and PC
      82 lines), and necrosis weighted more than apoptosis in contributing berberine's
      cytotoxicity. We demonstrated that mitochondrial protein cyclophilin-D (Cyp-D) is
      required for berberine-induced programmed necrosis. Inhibition of Cyp-D by its
      inhibitors cyclosporin A (CSA) or sanglifehrin A (SFA), and by Cyp-D shRNA
      depletion alleviated berberine-induced prostate cancer cell necrosis (but not
      apoptosis). Our data found that in prostate cancer cells, berberine induced
      reactive oxygen species (ROS) production, which dictated P53 translocation to
      mitochondria, where it physically interacted with Cyp-D to open mitochondrial
      permeability transition pore (mPTP). The anti-oxidant N-acetylcysteine (NAC), the
      P53 inhibitor pifithrin-alpha (PFTalpha) as well as P53 siRNA knockdown
      suppressed berberine-induced P53 mitochondrial translocation and Cyp-D
      association, thus inhibiting mitochondrial membrane potential (MMP) decrease and
      prostate cancer cell necrosis. In summary, the results of the present study
      provide mechanistic evidence that both apoptosis and programmed necrosis
      attribute to berberine's cytotoxicity in prostate cancer cells. 

PMID- 24946212
TI  - Transforming growth factor-beta (TGF-beta) induces the expression of
      chondrogenesis-related genes through TGF-beta receptor II (TGFRII)-AKT-mTOR
      signaling in primary cultured mouse precartilaginous stem cells.
AB  - Precartilaginous stem cells (PSCs) are adult stem cells which could initiate
      chondrocytes and bone growth. In the current study, we purified PSCs from the
      neonate mice' perichondrial mesenchyme through immunomagnetic beads with the
      fibroblast growth factor receptor-3 (FGFR-3) antibody. Mouse PSCs were seeded and
      cultured, and their phenotype was confirmed by FGFR-3 over-expression.
      Transforming growth factor-beta (TGF-beta) was added to induce PSCs
      differentiation. TGF-beta increased mRNA expression of chondrogenesis-related
      genes (collagen type II, Sox 9, and aggrecan) in the cultured PSCs, which was
      abolished by TGF-beta receptor II (TGFRII) lentiviral shRNA depletion. TGF-beta
      induced AKT activation in mouse PSCs, while the PI3K/AKT inhibitor (LY294002) and
      the AKT specific inhibitors (perifosine and MK-2206) largely suppressed TGF-beta
      induced collagen II, Sox 9, and aggrecan mRNA expression. Meanwhile, the mTOR
      complex 1 (mTORC1) blocker RAD001 or the mTORC1/2 dual inhibitor AZD-2014 also
      alleviated TGF-beta-induced chondrogenesis-associated genes expression. Further,
      lentiviral shRNA depletion of SIN1 (a mTORC2 component) or mTOR inhibited TGF
      beta's effect in the mouse PSCs. In conclusion, our evidence suggests that TGF
      beta induces the expression of chondrogenesis-related genes through TGFRII-AKT
      mTOR signaling in cultured mouse PSCs. 

PMID- 24946213
TI  - A new method to determine dispersive surface energy site distributions by inverse
      gas chromatography.
AB  - A computational model to predict the relative energy site contributions of a
      heterogeneous material from data collected by finite dilution-inverse gas
      chromatography (FD-IGC) is presented in this work. The methodology employed a
      multisolvent system site filling model utilizing Boltzmann statistics, expanding
      on previous efforts to calculate "experienced energies" at varying coverage,
      yielding a retention volume distribution allowing calculation of a surface free
      energy distribution. Surface free energy distributions were experimentally
      measured for racemic ibuprofen and beta-mannitol powders, the energies of each
      were found in the ranges 43-52 and 40-55 mJ/m(2), respectively, over a surface
      coverage range of 0-8%. The computed contributions to surface energy values were
      found to match closely with data collected on macroscopic crystals by alternative
      techniques (+/-<1.5 mJ/m(2)). 

PMID- 24946214
TI  - Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as
      proteasome inhibitors.
AB  - A new series of pseudopeptide boronate proteasome inhibitors (2-3) was developed,
      through optimization of our previously described analogs of bortezomib, bearing a
      bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological
      evaluation on human 20S proteasome displayed a promising inhibition profile,
      especially for compounds bearing a P2 ethylene fragment, which exhibited Ki
      values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 MUM)
      and considerable selectivity for proteasome over bovine pancreatic alpha
      chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the
      ligands are accommodated predominantly into the ChT-L site and that they
      covalently bind to the active site threonine residue via boron atom. Within the
      cellular assays performed against a 60 cancer cell line panel, compounds 3e and
      3f demonstrated also good antiproliferative activity and compound 3f emerged as
      promising lead compound for the development of anticancer agents targeting
      melanoma and non-small cell lung cancer. 

PMID- 24946215
TI  - Synthesis and structure-activity relationship of non-phosphorus-based fructose
      1,6-bisphosphatase inhibitors: 2,5-Diphenyl-1,3,4-oxadiazoles.
AB  - With the aim of discovering a novel class of non-phosphorus-based fructose-1,6
      bisphosphatase (FBPase) inhibitors, a series of 2,5-diphenyl-1,3,4-oxadiazoles
      were synthesized based on the hit compound (1) resulting from a high-throughput
      screening (HTS). Structure-activity relationship (SAR) studies led to the
      identification of several compounds with comparable inhibitory activities to AMP,
      the natural allosteric inhibitor of FBPase. Notably, compound 22 and 27b, bearing
      a terminal carboxyl or 1H-tetrazole, demonstrated remarkable inhibition to
      gluconeogenesis (GNG). In addition, both inhibition and binding mode to the
      enzyme were investigated by enzymatic kinetics and in silico experiments for
      representative compounds 16 and 22. 

PMID- 24946216
TI  - Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines
      as new antiplasmodial agents.
AB  - Thanks to a preliminary in vitro screening of several CCl3-substituted-nitrogen
      containing heterocycles belonging to our chemical library, the 2
      trichloromethylquinoxaline scaffold appeared to be of potential interest for
      developing new antiplasmodial agents. Then, combining these experimental results
      to the antimalarial properties reported for various pyrrolo[1,2-a]quinoxaline
      derivatives, an original series of fifteen 7-substituted-4
      trichoromethylpyrrolo[1,2-a]quinoxalines was synthesized in a 4 to 5 reaction
      steps pathway. All molecules were evaluated in vitro toward both their
      antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain
      and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were
      identified, displaying IC50 values in the micromolar range and low cytotoxicity
      values, reaching good selectivity indexes, in comparison with the reference drugs
      chloroquine and doxycycline. Structure-activity relationship studies showed that
      the pyrrolo[1,2-a]quinoxaline scaffold can support selective antiplasmodial
      activity when substituted at position 4 by a CCl3 group. However, substitution at
      position 7 of the same scaffold is neither beneficial for cytotoxicity nor
      favourable for the solubility in the biological media. 

PMID- 24946217
TI  - Tuning the antimicrobial pharmacophore to enable discovery of short lipopeptides
      with multiple modes of action.
AB  - Tryptophan and arginine rich antimicrobial peptides (AMPs) possess high potencies
      against both gram positive and gram negative bacteria, while lipopeptides
      represent another family of promising antimicrobial agents to combat invading
      pathogens. In the present study, we have synthesized a series of very short
      arginine, lysine and tryptophan containing lipopeptides and evaluated their
      antimicrobial activities against a panel of pathogenic microorganisms including
      Staphylococcus aureus, Escherichia coli, and Candida albicans. The results showed
      that most of these peptides were effective against tested strains with MIC values
      ranging from 3.9 to 62.5 MUg/mL. In addition to the small size, potent
      bactericidal activity, low to moderate hemolytic toxicity and membrane disruption
      ability, several peptides such as C10-RIKWWK and C10-RKWWK apparently retarded
      the migration of DNA on agarose gel in the DNA-binding assay, which implied the
      multiple modes of action in their bacteria-killing mechanism. These peptides
      revealed a promising therapeutic potential to develop as new antimicrobial
      agents. 

PMID- 24946219
TI  - Varicocele: early surgery versus observation.

PMID- 24946218
TI  - New modulatory pathways in micturition reflex function.

PMID- 24946220
TI  - Metastatic "burned-out" germ cell tumor of the testis.

PMID- 24946221
TI  - DNA copy number variations in patients with 46,XY disorders of sex development.
AB  - PURPOSE: Less than 50% of cases of 46,XY disorders of sex development are
      genetically defined after karyotyping and/or sequencing of known causal genes.
      Since copy number variations are often missed by karyotyping and sequencing, we
      assessed patients with unexplained 46,XY disorders of sex development using array
      comparative genomic hybridization for possible disease causing genomic variants.
      MATERIALS AND METHODS: DNA from unexplained cases of 46,XY disorders of sex
      development were tested by whole genome array comparative genomic hybridization.
      In cases where novel copy number variations were detected parental testing was
      performed to identify whether copy number variations were de novo or inherited.
      RESULTS: Of the 12 patients who underwent array comparative genomic hybridization
      testing 2 had possible copy number variations causing disorders of sex
      development, both maternally inherited microdeletions. One case, with a maternal
      history of premature ovarian failure, had a cosegregating microdeletion on 9q33.3
      involving NR5A1. The other case, with a maternal family history of congenital
      heart disease, had a cosegregating microdeletion on 8p23.1 upstream of GATA4.
      CONCLUSIONS: In this cohort copy number variations involving or adjacent to known
      causal genes led to 46,XY disorders of sex development in 2 of 12 previously
      unexplained cases (17%). Copy number variation testing is clinically indicated
      for unexplained cases of 46,XY disorders of sex development to aid in genetic
      counseling for family planning.

PMID- 24946222
TI  - Response to comment on "multi-tissue molecular, genomic, and developmental
      effects of the deepwater horizon oil spill on resident Gulf killifish (Fundulus
      grandis)".

PMID- 24946223
TI  - Proteomic analysis of ovarian proteins and characterization of thymosin-beta and
      RAC-GTPase activating protein 1 of the giant tiger shrimp Penaeus monodon.
AB  - Cellular proteomics of total proteins in ovaries of domesticated and wild giant
      tiger shrimp (Penaeus monodon) were examined using GeLC-MS/MS. In total, 1638
      proteins matched those previously deposited in databases and 1253 (76.50%) of
      these significantly matched known proteins. Several reproduction-related proteins
      (e.g. Cdc2, Cyclin B, Cdc25, 14-3-3, thymosin-beta and Rac-GTPase activating
      protein 1) were identified. In addition, the full-length cDNA of P. monodon
      thymosin-beta (PmTmsb; 1084 bp with an ORF of 387 bp and 128 deduced aa) and Rac
      GTPase activating protein 1 (PmRacgap1; an ORF of 1881 bp and 626 deduced aa)
      were further characterized. PmTmsb was constitutively expressed in all tissues.
      In contrast, PmRacgap1 was more abundantly expressed in gonads than in several
      non-reproductive tissues (e.g. subcuticular epithelium, hepatopancreas,
      intestine, pleopods, stomach and thoracic ganglion). The expression levels of
      PmTmsb and PmRacgap1 in ovaries of wild adult broodstock were significantly
      greater than those in ovaries of juveniles (P<0.05). However, their expression
      levels did not vary significantly during ovarian development stages in intact
      broodstock. However, eyestalk ablation resulted in a significant reduction in
      PmTmsb expression at stages I and III ovaries (P<0.05), although it did not
      affect PmRacgap1 transcription significantly at these stages. On the other hand,
      use of polyclonal antibodies derived from recombinant PmTmsb and PmRacgap1
      revealed that levels of both proteins decreased at the late stage (IV) of ovarian
      development. Our results suggested that PmTmsb and PmRacgap1 may act as negative
      effectors during ovarian development in P. monodon.

PMID- 24946225
TI  - Vacuolar biogenesis and aquaporin expression at early germination of broad bean
      seeds.
AB  - A key event in seed germination is water uptake-mediated growth initiation in
      embryonic axes. Vicia faba var. minor (broad bean) seeds were used for studying
      cell growth, vacuolar biogenesis, expression and function of tonoplast water
      channel proteins (aquaporins) in embryonic axes during seed imbibition, radicle
      emergence and growth. Hypocotyl and radicle basal cells showed vacuole
      restoration from protein storage vacuoles, whereas de novo vacuole formation from
      provacuoles was observed in cells newly produced by root meristem. cDNA fragments
      of seven novel aquaporin isoforms including five Tonoplast Intrinsic Proteins
      (TIP) from three sub-types were amplified by PCR. The expression was probed using
      q-RT-PCR and when possible with isoform-specific antibodies. Decreased expression
      of TIP3s was associated to the transformation of protein storage vacuoles to
      vacuoles, whereas enhanced expression of a TIP2 homologue was closely linked to
      the fast cell elongation. Water channel functioning checked by inhibitory test
      with mercuric chloride showed closed water channels prior to growth initiation
      and active water transport into elongating cells. The data point to a crucial
      role of tonoplast aquaporins during germination, especially during growth of
      embryonic axes, due to accelerated water uptake and vacuole enlargement resulting
      in rapid cell elongation. 

PMID- 24946224
TI  - Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is
      important for parasite fitness in vivo.
AB  - Trypanosoma brucei is a unicellular parasite that causes sleeping sickness in
      humans. Most of its transcription is constitutive and driven by RNA polymerase
      II. RNA polymerase I (Pol I) transcribes not only ribosomal RNA genes, but also
      protein-encoding genes, including variant surface glycoproteins (VSGs) and
      procyclins. In T. brucei, histone H1 (H1) is required for VSG silencing and
      chromatin condensation. However, whether H1 has a genome-wide role in
      transcription is unknown. Here, using RNA sequencing we show that H1 depletion
      changes the expression of a specific cohort of genes. Interestingly, the
      predominant effect is partial loss of silencing of Pol I loci, such as VSG and
      procyclin genes. Labelling of nascent transcripts with 4-thiouridine showed that
      H1 depletion does not alter the level of labelled Pol II transcripts. In
      contrast, the levels of 4sU-labelled Pol I transcripts were increased by two- to
      sixfold, suggesting that H1 preferentially blocks transcription at Pol I loci.
      Finally, we observed that parasites depleted of H1 grow almost normally in
      culture but they have a reduced fitness in mice, suggesting that H1 is important
      for host-pathogen interactions.

PMID- 24946226
TI  - Effect of topical sucralfate vs clindamycin on posttonsillectomy pain in children
      aged 6 to 12 years: a triple-blind randomized clinical trial.
AB  - IMPORTANCE: Postoperative sore throat is one of the most common problems after
      tonsillectomy. Antibiotics remove the local flora and reduce inflammation and
      thus may reduce postoperative pain after tonsillectomy. OBJECTIVE: To assess the
      effect of topical sucralfate and clindamycin on local pain reduction after
      tonsillectomy in children aged 6 to 12 years. DESIGN, SETTING, AND PARTICIPANTS:
      Triple-blind randomized clinical trial of children aged 6 to 12 years with sleep
      apnea or snoring due to adenotonsillar hypertrophy and chronic airway obstruction
      or with chronic infections who were candidates for tonsillectomy at Besat
      Hospital, Hamadan University of Medical Sciences, from May to October 2013.
      INTERVENTIONS: Patients were randomly assigned to receive sucralfate mouthwash,
      clindamycin mouthwash, or placebo (cellulose). The oral cavity was washed before
      and immediately after surgery with 10 mL of the prepared solution for 1 minute
      and then suctioned. Then, 8 hours after surgery, the patients were asked to keep
      10 mL of the prepared mouthwash solution in their mouths for 1 minute 3 times a
      day for 3 days. MAIN OUTCOMES AND MEASURES: Postoperative sore throat evaluated
      daily for 5 days using the Faces Pain Scale-Revised. RESULTS: Of 110 patients
      enrolled, 101 patients remained for analysis. Patients in the placebo group had
      significantly higher mean (SD) throat pain scores than did patients in both drug
      groups on postsurgery days 1 through 4. Day 1 scores were 8.00 (1.84) for placebo
      and 6.00 (1.84) for sucralfate and 6.79 (1.87) for clindamycin (P = .001). Pain
      scores were not significantly different on day 5. Acetaminophen use was more
      common in the placebo group on days 3 and 4 (2.97 and 2.44) vs the sucralfate
      group (2.24 and 2.15) and the clindamycin group (2.36 and 2.12) (P = .001 and
      .02, respectively). Bleeding on day 1 was more common in the placebo group (3 of
      34) vs none in the drug groups. Food intolerance on day 1 was less common in
      patients receiving sucralfate (2 of 34) than placebo (9 of 34) or clindamycin (11
      of 33) (P = .02). There was no significant difference among the 3 groups in
      numbers of episodes of nocturnal waking, halitosis, earache, nausea, and
      vomiting. CONCLUSIONS AND RELEVANCE: This trial indicated that topical sucralfate
      and clindamycin are safe drugs with no important adverse effects that can
      significantly reduce posttonsillectomy pain in children and help them return to
      normal life sooner. TRIAL REGISTRATION: Iranian Registry of Clinical Trials
      registration number: IRCT201303209014N16.

PMID- 24946227
TI  - Effects of a structural intervention and implementation on physical activity
      among youth in residential children's homes.
AB  - This study reports the effects of a structural intervention, ENRICH
      (Environmental Interventions in Children's Homes) which targeted the physical and
      social environment within residential children's homes (RCHs) to increase
      physical activity (PA) among residents (n=799). Participating RCHs (n=29) were
      randomized to Early (n=17) or Delayed (n=12) groups from 2004 to 2006 and 2006 to
      2008, respectively. Children's PA was measured at three time periods (2004, 2006,
      2008). Intent-to-treat analysis revealed no intervention impact on PA. Subsequent
      analyses used process evaluation data to group organizations into high and low PA
      promoting RCHs to compare PA level, controlling for assignment to condition.
      Organizations with high PA-promoting environments were found to have more active
      youth. Utility of a comprehensive implementation monitoring plan and the need for
      formative assessment of organizational capacity is discussed. 

PMID- 24946228
TI  - Capillary dysfunction and impaired tissue oxygenation in complex regional pain
      syndrome: a hypothesis.

PMID- 24946230
TI  - Have we forgotten about the needs of children?

PMID- 24946231
TI  - Experimental study of the cooperativity of CH-pi interactions.
AB  - A series of new torsional molecular balances was designed to study the
      cooperativity of CH-pi interaction in the solid state and in solution. The
      measured interaction energies correlated better to the number of participating
      alkyl carbons than to the number of CH-pi contacts. The methyl and ethyl groups
      displayed additive interaction energies. However, the branched isopropyl group
      displayed strong positive cooperativity with higher than predicted interaction
      energies. 

PMID- 24946229
TI  - Engineering protein farnesyltransferase for enzymatic protein labeling
      applications.
AB  - Creating covalent protein conjugates is an active area of research due to the
      wide range of uses for protein conjugates spanning everything from biological
      studies to protein therapeutics. Protein Farnesyltransferase (PFTase) has been
      used for the creation of site-specific protein conjugates, and a number of PFTase
      substrates have been developed to facilitate that work. PFTase is an effective
      catalyst for protein modification because it transfers Farnesyl diphosphate (FPP)
      analogues to protein substrates on a cysteine four residues from the C-terminus.
      While much work has been done to synthesize various FPP analogues, there are few
      reports investigating how mutations in PFTase alter the kinetics with these
      unnatural analogues. Herein we examined how different mutations within the PFTase
      active site alter the kinetics of the PFTase reaction with a series of large FPP
      analogues. We found that mutating either a single tryptophan or tyrosine residue
      to alanine results in greatly improved catalytic parameters, particularly in
      kcat. Mutation of tryptophan 102beta to alanine caused a 4-fold increase in kcat
      and a 10-fold decrease in KM for a benzaldehyde-containing FPP analogue resulting
      in an overall 40-fold increase in catalytic efficiency. Similarly, mutation of
      tyrosine 205beta to alanine caused a 25-fold increase in kcat and a 10-fold
      decrease in KM for a coumarin-containing analogue leading to a 300-fold increase
      in catalytic efficiency. Smaller but significant changes in catalytic parameters
      were also obtained for cyclo-octene- and NBD-containing FPP analogues. The latter
      compound was used to create a fluorescently labeled form of Ciliary Neurotrophic
      Factor (CNTF), a protein of therapeutic importance. Additionally, computational
      modeling was performed to study how the large non-natural isoprenoid analogues
      can fit into the active sites enlarged via mutagenesis. Overall, these results
      demonstrate that PFTase can be improved via mutagenesis in ways that will be
      useful for protein engineering and the creation of site-specific protein
      conjugates. 

PMID- 24946232
TI  - On the consequences of aluminium stress in rye: repression of two mitochondrial
      malate dehydrogenase mRNAs.
AB  - Plants have developed several external and internal aluminium (Al) tolerance
      mechanisms. The external mechanism best characterised is the exudation of organic
      acids induced by Al. Rye (Secale cereale L.), one of the most Al-tolerant cereal
      crops, secretes both citrate and malate from its roots in response to Al.
      However, the role of malate dehydrogenase (MDH) genes in Al-induced stress has
      not been studied in rye. We have isolated the ScMDH1 and ScMDH2 genes, encoding
      two different mitochondrial MDH isozymes, in three Al-tolerant rye cultivars
      (Ailes, Imperial and Petkus) and one sensitive inbred rye line (Riodeva). These
      genes, which have seven exons and six introns, were located on the 1R (ScMDH1)
      and 3RL (ScMDH2) chromosomes. Exon 1 of ScMDH1 and exon 7 of ScMDH2 were the most
      variable among the different ryes. The hypothetical proteins encoded by these
      genes were classified as putative mitochondrial MDH isoforms. The phylogenetic
      relationships obtained using both cDNA and protein sequences indicated that the
      ScMDH1 and ScMDH2 proteins are orthologous to mitochondrial MDH1 and MDH2
      proteins of different Poaceae species. The expression studies of the ScMDH1 and
      ScMDH2 genes indicate that it is more intense in roots than in leaves. Moreover,
      the amount of their corresponding mRNAs in roots from plants treated and not
      treated with Al was higher in the tolerant cultivar Petkus than in the sensitive
      inbred line Riodeva. In addition, ScMDH1 and ScMDH2 mRNA levels decreased in
      response to Al stress (repressive behaviour) in the roots of both the tolerant
      Petkus and the sensitive line Riodeva. 

PMID- 24946233
TI  - Signal detection based on time-to-onset: extending a new method from spontaneous
      reports to observational studies.
AB  - PURPOSE: A proof-of-concept study has previously highlighted the added value of a
      method using time-to-onset (TTO) for quantitative and non-parametric signal
      detection on spontaneous report data. The aim of this study was to assess the
      added value of this new TTO signal detection method adapted to observational
      studies. METHODS: For each adverse event collected during the conduct of an
      observational study of H1N1 pandemic influenza vaccine, the TTO distribution was
      tested against the 'follow-up distribution' from vaccination to 'lost to follow
      up' by a Kolmogorov-Smirnov test. Events rejecting the null hypothesis of similar
      distribution were flagged as signals, and a safety physician evaluated their
      relevance for further medical assessment. We simulated ongoing surveillance by
      performing retrospective weekly signal detection based on TTO. RESULTS: The TTO
      method detected 21, 15 and 4 signals within a 30-day period post-dose 1 with
      confidence levels set at 90%, 95% and 99%, respectively. Of these signals, 14
      (67%), 10 (67%) and 2 (50%) were considered as relevant. Among the 14, six had
      not been identified by previous signal detection activities. When performed
      weekly, the Kolmogorov-Smirnov test detected 26 events as signals (alpha = 0.05).
      Three weeks after first participant first dose, one of the six new signals could
      theoretically have been detected. CONCLUSIONS: This study provided evidence that
      the Kolmogorov-Smirnov method can screen all TTO distributions and objectively
      flag the unexpected, leading to earlier detection of signals, and thus potential
      safety issues.

PMID- 24946234
TI  - Use of isotope dilution method to predict bioavailability of organic pollutants
      in historically contaminated sediments.
AB  - Many cases of severe environmental contamination arise from historical episodes,
      where recalcitrant contaminants have resided in the environment for a prolonged
      time, leading to potentially decreased bioavailability. Use of bioavailable
      concentrations over bulk chemical levels improves risk assessment and may play a
      critical role in determining the need for remediation or assessing the
      effectiveness of risk mitigation operations. In this study, we applied the
      principle of isotope dilution to quantify bioaccessibility of legacy contaminants
      DDT and PCBs in marine sediments from a Superfund site. After addition of 13C or
      deuterated analogues to a sediment sample, the isotope dilution reached a steady
      state within 24 h of mixing. At the steady state, the accessible fraction (E)
      derived by the isotope dilution method (IDM) ranged from 0.28 to 0.89 and was
      substantially smaller than 1 for most compounds, indicating reduced availability
      of the extensively aged residues. A strong linear relationship (R2=0.86) was
      found between E and the sum of rapid (Fr) and slow (Fs) desorption fractions
      determined by sequential Tenax desorption. The IDM-derived accessible
      concentration (Ce) was further shown to correlate closely with tissue residue in
      the marine benthic polychaete Neanthes arenaceodentata exposed in the same
      sediments. As shown in this study, the IDM approach involves only a few simple
      steps and may be readily adopted in laboratories equipped with mass
      spectrometers. This novel method is expected to be especially useful for
      historically contaminated sediments or soils, for which contaminant
      bioavailability may have changed significantly due to aging and other
      sequestration processes.

PMID- 24946236
TI  - The impact of involuntary exit from employment in later life on the risk of major
      depression and being prescribed anti-depressant medication.
AB  - OBJECTIVES: Involuntary employment exit in later life has been shown to be a risk
      factor for poor physical and mental health. This study aims to examine the
      relationship between involuntary employment exit in later life and subsequent
      risk of reporting major depression or being prescribed anti-depressant medication
      (ADM). METHOD: Data were drawn from four waves of the Swedish Longitudinal
      Occupational Survey of Health (SLOSH). This is a nationally representative
      longitudinal cohort survey of persons employed in Sweden in 2003 and 2005. The
      sample was restricted to respondents who had exited the labour market aged 50+
      years between 2006 and 2012 (N = 1433). Major depression was measured using the
      Symptom Checklist Core Depression Scale (SCL-CD6). Prescription ADM redeemed from
      a pharmacy was based on the National Prescribed Drug Register. RESULTS: After
      controlling for socio-demographic variables, health, health behaviours, and
      baseline depression, involuntary employment exit was associated with an increased
      risk of reporting major depression (OR 3.16; CI 1.32-7.61) and becoming newly
      prescribed ADM (HR 2.08; CI 1.03-4.21) compared to voluntary employment exit.
      CONCLUSION: Involuntary employment exit represents a risk for subsequent
      depression in later life. Mental health and social services ought to consider
      identifying these individuals for possible intervention programs to reduce the
      burden of depression in later life.

PMID- 24946237
TI  - Management of pain on hallux valgus with percutaneous intra-articular Pulse-Dose
      Radiofrequency.
AB  - AIM: The purpose of our study was to investigate the role of intra-articular
      pulse-dose radiofrequency in management of painful hallux valgus refractory to
      conservative therapies. METHOD: Between November 2010 and April 2012, 51 patients
      (15 male, 36 female) with a median age of 71.4 years were included in our
      clinical trial. Under fluoroscopic guidance we introduced a 22 gauge 10 cm length
      cannula by a percutaneous access in the first metatarsophalangeal joint and its
      tip was placed intra-articularly. After removing the spindle, a radiofrequency
      needle with a 5 mm active tip was introduced. The following parameters were used:
      1200 pulses at high voltage (45 V) with 20 msec duration followed by 480 msec
      silent phases. RESULTS: A great reduction in pain intensity was documented at 1
      week, 1 month and 3 months after procedures. Pain intensity increased between 5
      and 8 months after treatments, so we performed a second procedure in all patients
      between 7 months and 9 months since the first treatment. Also in this case we
      obtained a great reduction of pain intensity in the first 3 months after the
      procedure. Pain intensity returned at preprocedural values after 9 months after
      second procedure. No complications were observed. CONCLUSION: Our experience
      shows pulse-dose radiofrequency is a safe, repeatable and effective technique for
      managing patients with symptomatic hallux valgus in the short and medium term.
      Pulse-dose radiofrequency may improve pain control and quality of life in
      patients with hallux valgus refractory to conservative therapies.

PMID- 24946235
TI  - A role for Drosophila Cyclin J in oogenesis revealed by genetic interactions with
      the piRNA pathway.
AB  - Cyclin J (CycJ) is a poorly characterized member of the Cyclin superfamily of
      cyclin-dependent kinase regulators, many of which regulate the cell cycle or
      transcription. Although CycJ is conserved in metazoans its cellular function has
      not been identified and no mutant defects have been described. In Drosophila,
      CycJ transcript is present primarily in ovaries and very early embryos,
      suggesting a role in one or both of these tissues. The CycJ gene (CycJ) lies
      immediately downstream of armitage (armi), a gene involved in the Piwi-associated
      RNA (piRNA) pathways that are required for silencing transposons in the germline
      and adjacent somatic cells. Mutations in armi result in oogenesis defects but a
      role for CycJ in oogenesis has not been defined. Here we assessed oogenesis in
      CycJ mutants in the presence or absence of mutations in armi or other piRNA
      pathway genes. CycJ null ovaries appeared normal, indicating that CycJ is not
      essential for oogenesis under normal conditions. In contrast, armi null ovaries
      produced only two egg chambers per ovariole and the eggs had severe axis
      specification defects, as observed previously for armi and other piRNA pathway
      mutants. Surprisingly, the CycJ armi double mutant failed to produce any mature
      eggs. The double null ovaries generally had only one egg chamber per ovariole and
      the egg chambers frequently contained an overabundance of differentiated germline
      cells. Production of these compound egg chambers could be suppressed with CycJ
      transgenes but not with mutations in the checkpoint gene mnk, which suppress
      oogenesis defects in armi mutants. The CycJ null showed similar genetic
      interactions with the germline and somatic piRNA pathway gene piwi, and to a
      lesser extent with aubergine (aub), a member of the germline-specific piRNA
      pathway. The strong genetic interactions between CycJ and piRNA pathway genes
      reveal a role for CycJ in early oogenesis. Our results suggest that CycJ is
      required to regulate egg chamber production or maturation when piRNA pathways are
      compromised. 

PMID- 24946238
TI  - Ephrin receptor A10 is a promising drug target potentially useful for breast
      cancers including triple negative breast cancers.
AB  - Ephrin receptor A10 (EphA10) is a relatively uncharacterized protein which is
      expressed in many breast cancers but not expressed in normal breast tissues.
      Here, we examined the potential of EphA10 as a drug target in breast cancer.
      Immunohistochemical staining of clinical tissue sections revealed that EphA10 was
      expressed in various breast cancer subtypes, including triple negative breast
      cancers (TNBCs), with no expression observed in normal tissues apart from testis.
      Ligand-dependent proliferation was observed in EphA10-transfected MDA-MB-435
      cells (MDA-MB-435(EphA10)) and native TNBC cells (MDA-MB-436). However, this
      phenomenon was not observed in parental MDA-MB-435 cells which express a low
      level of EphA10. Finally, tumor growth was significantly suppressed by
      administration of an anti-EphA10 monoclonal antibody in a xenograft mouse model.
      These results suggest that inhibition of EphA10 signaling may be a novel
      therapeutic option for management of breast cancer, including TNBCs which are
      currently not treated with molecularly targeted agents. 

PMID- 24946240
TI  - Editorial.

PMID- 24946241
TI  - Suicide and the elderly.
AB  - Impending demographic changes mean that the proportion of the elderly in the
      population will increase. Suicide rates increase with age. The literature on
      elderly suicide, with emphasis on methodology, cross-national rates and trends,
      correlates, cultural factors, location and method, attempted suicides and
      prevention, is critically reviewed in this paper. 

PMID- 24946242
TI  - The serotonin paradox: Negative symptoms and SSRI augmentation.
AB  - Negative symptoms of schizophrenia are often difficult to treat and may be
      associated with poorer long-term outcome. As depressive and negative symptoms
      show some overlap, augmentation of neuroleptics by antidepressants has repeatedly
      been investigated for efficacy against negative symptoms in schizophrenic
      patients. Studies on SSRI augmentation of neuroleptic medication reveal some
      evidence for increased efficacy of conventional antipsychotics in negative
      symptoms after addition of SSRIs. Since no correlation could be found between
      improvement of negative symptoms on the one hand and positive, depressive or
      extrapyramidal motor symptoms on the other, a direct effect seems likely. SSRIs
      may therefore be an alternative to clozapine, especially in patients for whom
      there are contraindications against clozapine treatment. As yet, there is no
      convincing rationalization for the paradox that both serotonergic and
      antiserotonergic substances, e.g. atypical antipsychotics, may improve negative
      symptoms. 

PMID- 24946243
TI  - A systematized approach to the management of the depressed and anxious patient.
AB  - The coexistence of depression and anxiety is a common occurrence that frequently
      poses diagnostic and treatment challenges in the clinical setting. As
      epidemiological studies continue to confirm the enormous prevalence of this
      comorbid condition, the separation in diagnosis and treatment between depression
      and anxiety has become increasingly less pronounced. Additionally, the discovery
      that pharmacotherapeutic modalities have a broader range of efficacy, often
      overlapping both depression and anxiety, has led to an evolving reclassification
      of treatment, away from 'antidepressants' and 'anxiolytics' toward one based on
      mechanism of action. A rational approach to the systematized management of the
      various comorbidities of depressive and anxiety disorders is discussed. 

PMID- 24946244
TI  - Benzodiazepine dependence: Avoidance and withdrawal.
AB  - Benzodiazepine dependence remains a shadowy concept. Dependence undoubtedly
      exists but also acts as an umbrella concept for the underlying chronic morbidity
      associated with neurosis. Treatment should be directed at early detection and
      vigorous treatment of anxiety disorders; and an acceptance that long-term
      treatment may be necessary. Once benzodiazepine dependence is established, each
      patient requires careful evaluation to establish their unique problem and to
      institute individual treatment plans. Strategies for benzodiazepine withdrawal
      are documented but each has its own problems and success can only be achieved if
      underlying problems are dealt with as well as simply providing tranquilliser
      withdrawal. 

PMID- 24946239
TI  - Protein post-translational modifications and misfolding: new concepts in heart
      failure.
AB  - A new concept in the field of heart-failure (HF) research points to a role of
      misfolded proteins, forming preamyloid oligomers (PAOs), in cardiac toxicity.
      This is largely based on few studies reporting the presence of PAOs, similar to
      those observed in neurodegenerative diseases, in experimental and human HF. As
      the majority of proteinopathies are sporadic in nature, protein post
      translational modifications (PTMs) likely play a major role in this growing class
      of diseases. In fact, PTMs are known regulators of protein folding and of the
      formation of amyloid species in well-established proteinopathies. Proteomics has
      been instrumental in identifying both chemical and enzymatic PTMs, with a
      potential impact on protein mis-/folding. Here we provide the basics on how
      proteins fold along with a few examples of PTMs known to modulate protein
      misfolding and aggregation, with particular focus on the heart. Due to its
      innovative content and the growing awareness of the toxicity of misfolded
      proteins, an "Alzheimer's theory of HF" is timely. Moreover, the continuous
      innovations in proteomic technologies will help pinpoint PTMs that could
      contribute to the process. This nuptial between biology and technology could
      greatly assist in identifying biomarkers with increased specificity as well as
      more effective therapies.

PMID- 24946245
TI  - Effectiveness of valproate on delirium and/or aggressive behavior in demented
      patients: A practical pilot study.
AB  - This open study was designed to evaluate the efficacy of valproate as a treatment
      for delirium and/or aggressive behavior in patients with dementia. Of the
      patients who participated, nine had vascular dementia, two had Alzheimer's
      disease, one had Parkinson's disease and one had alcohol dependence, all meeting
      DSM-IH-R criteria for dementia. In these 13 patients, delirium in seven and
      aggressive behavior in 12 patients were the target symptoms of this study.
      Valproate was administered orally at a dose of 200-600 mg daily (mean 526 mg,
      sd=20.4) without changing the dose of the other medications. The effect of
      valproate on delirium and aggressive behavior was evaluated with the Delirium
      Rating Scale (DRS) and Gottfries-Brane-Steen Scale (GBS). The total DRS scores
      decreased in 6/7 patients with delirium (P < 0.05) within 2 weeks. There were
      significant diferences between the score variances (before and during treatment)
      of the three categories in the GBS scale: emotional lability (P < 0.01),
      irritability (P < 0.01) and restlessness (P < 0.01). These findings suggest the
      effectiveness of valproate treatment for delirium and/or aggressive behavior in
      demented patients. 

PMID- 24946246
TI  - Psychiatric disorder in essential dyspepsia.
AB  - We wanted to examine the prevalence of psychiatric morbidity in patients
      diagnosed as having essential dyspepsia, as well as the short-term course of
      dyspeptic symptoms, following drug treatment of the psychiatric condition.
      Seventy-four patients with essential dyspepsia presenting to the gastroenterology
      outpatient department of a medical college were investigated for the presence of
      psychiatric disorder. The response to an open trial of pharmacotherapy in 50
      patients with a psychiatric disorder and no other demonstrable pathology was
      assessed. These patients met the criteria for a DSM-III-R diagnosis, most
      commonly major depressive disorder (26) or generalized anxiety disorder (10). The
      mean age of those with a psychiatric disorder alone was significantly higher than
      that of those with another demonstrable pathology. With treatment, 16 patients
      with no demonstrable pathology other than psychiatric disorder (depression: 12;
      anxiety: 4) showed improvement over a period of 6 weeks in psychiatric as well as
      dyspepsia ratings. The difference was however statistically significant only for
      the group with major depressive disorder. We concluded that, despite differences
      in the characteristics of the population studied, a psychiatric diagnosis is
      associated with at least a proportion of cases with essential dyspepsia and
      emerges as a likely explanation. 

PMID- 24946247
TI  - Change of mood during sleep and REM sleep variables.
AB  - Polysomnography was performed during two consecutive nights in 23 patients with
      major depression. After every final awakening patients estimated the change of
      their mood from evening to morning: 1. Mood worse in the morning than in the
      evening; 2. Mood does not change; 3. Mood better in the morning. When mood was
      estimated as being better in the morning (20% of all nights), eye movement
      density in REM sleep increased from the first to the fourth cycle. In all other
      nights eye movement density was slightly higher in the first than in subsequent
      cycles. Mood improvement correlated positively with eye movement density in the
      fourth cycle and negatively with REM sleep duration in the first cycle. Eye
      movement density in the first cycle correlated positively with the subjective
      estimation of sleep latency. A possible functional difference between initial and
      final REM sleep periods is proposed. 

PMID- 24946249
TI  - A case of periodic catatonia, due to frontal lobe epilepsy.
AB  - A case history is presented in which acute periodic catatonia was caused by
      frontal lobe epilepsy. This manifestation of frontal lobe epilepsy has not, to
      the authors' knowledge, been described before. The authors mention the problems
      of diagnosis and discuss a possible pathogenetic mechanism for the capricious
      presentation in this patient. 

PMID- 24946248
TI  - Clozapine-induced myoclonic seizures and valproic acid.
AB  - Within a 3-year period, in 220 patients receiving clozapine, we observed
      myoclonic seizures in two who had no previous epileptic history. Seizures
      appeared at the titration phase at relatively low doses, and resolved with the
      addition of valproic acid, allowing further increases of the clozapine dose to
      therapeutic levels. 

PMID- 24946250
TI  - Periodic menstruation-linked psychosis of adolescence.
AB  - Clinical reports of a psychosis with distinct presentation affecting adolescent
      girls have appeared sporadically over more than a century, but its specificity
      has not been fully recognized. The literature is briefly reviewed and our
      experience with 11 such patients is presented. Periodic Menstruation-Linked
      Psychosis of Adolescence (PMLPA) appears to have a clinical picture which differs
      from that of any other form of psychosis, and to respond to different therapeutic
      regimes being at the same time totally unresponsive to traditional antipsychotic
      drugs. This makes the syndrome distinct, specific and highly treatable and
      therefore its recognition is of considerable clinical importance. 

PMID- 24946251
TI  - A dementia story with a happier ending.
AB  - A case is described of a 77-year-old lady who was diagnosed as having Parkinson's
      disease and was treated with antiparkinsonian drugs over a year with little
      effect. She was subsequently referred to a psychiatrist because of her aggressive
      outbursts and marked changes in personality. Investigations showed that she
      suffered from normal pressure hydrocephalus (NPH), and the insertion of a
      ventriculo-peritoneal shunt (VPS) led to a resolution of most of her problems,
      physical as well as mental. 

PMID- 24946252
TI  - A patient who changed my practice: Personality disorder or bipolar disorder?
AB  - The case of a man originally diagnosed as having a personality disorder is
      presented. Follow-up over many years revealed that he was really suffering from a
      bipolar manic-depressive disorder which responded well to lithium. His later life
      was characterized by stability. 

PMID- 24946255
TI  - One-step fabrication of functionalized magnetic adsorbents with large surface
      area and their adsorption for dye and heavy metal ions.
AB  - Functionalized magnetic adsorbents (FMAs) were synthesized by a facile and
      surfactant-free one-pot solvothermal approach, using iron(III) chloride
      hexahydrate as the precursor, ethylene glycol as the reducing agent, ammonium
      acetate, and EDTA-2Na as an electrostatic stabilization agent. The self-assembly
      process of the functionalized magnetic adsorbents has been investigated and a
      plausible mechanism is proposed. The resulting functionalized magnetic adsorbents
      have relatively high specific surface areas (71.6 m(2) g(-1)), excellent magnetic
      properties and rich functional groups (carboxyl groups, hydroxyl groups and
      hydrophobic groups). Meanwhile, the resulting FMAs were employed in the
      adsorption of dyes and heavy metal ions from aqueous solution. Herein, we took
      two types of typical pollutants, dyes (methylene blue (MB) and malachite green
      (MG)) and toxic heavy metal ions (Cr(VI) and Pb(II)) as examples of organic and
      inorganic pollutants in environmental water. The excellent intrinsic properties
      of the FMAs led to a stronger adsorption ability than a solid Fe3O4 adsorbent for
      MB, MG, Cr(VI) and Pb(II). Especially, the simultaneous adsorption of the
      functionalized flower-like magnetic adsorbents for MG and Pb(II) was also
      determined in a binary system. Finally, it was demonstrated that the resulting
      flower-like magnetic adsorbents are expected to be a good candidate as an
      adsorbent for water treatment.

PMID- 24946254
TI  - Exploring inflammatory disease drug effects on neutrophil function.
AB  - Neutrophils are critical inflammatory cells; thus, it is important to
      characterize the effects of drugs on neutrophil function in the context of
      inflammatory diseases. Herein, chemically guided neutrophil migration, known as
      chemotaxis, is studied in the context of drug treatment at the single cell level
      using a microfluidic platform, complemented by cell viability assays and calcium
      imaging. Three representative drugs known to inhibit surface receptor expression,
      signaling enzyme activity, and the elevation of intracellular Ca(2+) levels, each
      playing a significant role in neutrophil chemotactic pathways, are used to
      examine the in vitro drug effects on cellular behaviors. The microfluidic device
      establishes a stable concentration gradient of chemokines across a cell culture
      chamber so that neutrophil migration can be monitored under various drug-exposure
      conditions. Different time- and concentration-dependent regulatory effects were
      observed by comparing the motility, polarization, and effectiveness of neutrophil
      chemotaxis in response to the three drugs. Viability assays revealed distinct
      drug capabilities in reducing neutrophil viability while calcium imaging
      clarified the role of Ca(2+) in the neutrophil chemotaxis. This study provides
      mechanistic insight into the drug effects on neutrophil function, facilitating
      comparison of current and potential pharmaceutical approaches. 

PMID- 24946256
TI  - Missing a follow-up after mild traumatic brain injury--does it matter?
AB  - OBJECTIVE: This study sought to identify potential differing clinical
      characteristics between patients with a mild traumatic brain injury (MTBI) who
      attended a planned follow-up session and not. This study investigated whether
      clinical characteristics and attendance for a planned follow-up service 2-months
      after injury could be related to return-to-work (RTW) 1-year later. METHOD:
      Prospective cohort study of 343 patients with MTBI admitted consecutively to the
      Department of Neurosurgery in 2009-2011. Demographic and clinical data were
      obtained from the hospital files and data about sick leave from The Norwegian
      Labour and Welfare Service. Patients were categorized into two groups according
      to their attendance. RESULTS: One hundred and sixty-one (67%) patients attended
      (AG) and 80 (33%) did not (NAG) attend their follow-up appointments. The AG had
      significantly more frequently intracranial pathology on CT scan, had consumed
      less alcohol and were older. Logistic regression showed that follow-up attendance
      (OR = 16.89) and sick leave before injury (OR = 9.70) are unfavourably related to
      RTW at 12-months. Skull fracture and cause of injury had no influence of the
      outcome. CONCLUSION: Not attending the follow-up has a favourable outcome after
      MBTI, indicating that these patients have a reduced need for medical and
      rehabilitation support for their brain injury.

PMID- 24946258
TI  - Poly beta-cyclodextrin inclusion-induced formation of two-photon fluorescent
      nanomicelles for biomedical imaging.
AB  - A novel two-photon absorption (TPA) nanomicelle through the "host-guest"
      chemistry has been developed and successfully applied in tumor tissue imaging in
      this work. 

PMID- 24946259
TI  - A Bayesian network decision model for supporting the diagnosis of dementia,
      Alzheimer's disease and mild cognitive impairment.
AB  - Population aging has been occurring as a global phenomenon with heterogeneous
      consequences in both developed and developing countries. Neurodegenerative
      diseases, such as Alzheimer's Disease (AD), have high prevalence in the elderly
      population. Early diagnosis of this type of disease allows early treatment and
      improves patient quality of life. This paper proposes a Bayesian network decision
      model for supporting diagnosis of dementia, AD and Mild Cognitive Impairment
      (MCI). Bayesian networks are well-suited for representing uncertainty and
      causality, which are both present in clinical domains. The proposed Bayesian
      network was modeled using a combination of expert knowledge and data-oriented
      modeling. The network structure was built based on current diagnostic criteria
      and input from physicians who are experts in this domain. The network parameters
      were estimated using a supervised learning algorithm from a dataset of real
      clinical cases. The dataset contains data from patients and normal controls from
      the Duke University Medical Center (Washington, USA) and the Center for
      Alzheimer's Disease and Related Disorders (at the Institute of Psychiatry of the
      Federal University of Rio de Janeiro, Brazil). The dataset attributes consist of
      predisposal factors, neuropsychological test results, patient demographic data,
      symptoms and signs. The decision model was evaluated using quantitative methods
      and a sensitivity analysis. In conclusion, the proposed Bayesian network showed
      better results for diagnosis of dementia, AD and MCI when compared to most of the
      other well-known classifiers. Moreover, it provides additional useful information
      to physicians, such as the contribution of certain factors to diagnosis. 

PMID- 24946260
TI  - Bismuth(III) triflate-catalyzed synthesis of substituted 2-alkenylfurans.
AB  - A convergent synthesis of the title compounds is reported, which relies on a
      successive 2-fold SN'-type substitution reaction at methoxy-substituted
      propargylic acetates. The furan C3-C4 bond is presumably established by silyl
      enol ether attack at a propargylic cation intermediate. The resulting alpha
      methoxyallene is intramolecularly substituted, leading to cyclization by
      displacement of the methoxy group (O-C2 bond formation) and to simultaneous
      formation of the exocyclic alkene double bond. Despite the relatively mild
      conditions, the reactions were complete within 5 min. 

PMID- 24946262
TI  - Long-term adsorption kinetics of asphaltenes at the oil-water interface: a random
      sequential adsorption perspective.
AB  - Previous studies indicated that asphaltenes adsorbed as monomers on oil-water
      interfaces and the early stage kinetics of the process was controlled by
      diffusion and hence dependent on oil viscosity. By measuring interfacial tension
      (IFT) as a function of surface coverage during droplet expansions in pendant drop
      experiments, it was also concluded that the IFT data could be interpreted with a
      Langmuir equation of state (EoS), which was independent of oil viscosity, time of
      adsorption, and bulk asphaltenes concentration. The surface excess coverage was
      calculated to be ~0.3 nm(2)/molecule, which suggested adsorption in face-on
      configuration of asphaltenes monomers at the interface and average PAH core per
      molecule of about 6 for the asphaltenes investigated, consistent with the Yen
      Mullins model. The current study focuses on the kinetics of asphaltenes
      adsorption at longer times and higher interfacial coverage. Long-term IFT data
      have been measured by the pendant drop method for different asphaltenes
      concentrations and for different bulk viscosities of the oil phase (0.5-28 cP).
      The data indicate that when coverage reaches 35-40%, the adsorption rates slow
      down considerably compared to the diffusion-controlled rates at the very early
      stages. The surface pressure increase rate (or IFT decrease rate) at these higher
      coverages is now independent of oil viscosity but dependent upon both surface
      pressure itself and asphaltene monomer concentration. The long-term asymptotic
      behavior of surface coverage is found to be consistent with the predictions from
      surface diffusion-mediated random sequential adsorption (RSA) theory which
      indicates a linear dependency of surface coverage on 1/?t and an asymptotic limit
      very close to 2D random close packing of polydispersed disks (85%). From these
      observations RSA theory parameters were extracted that enabled description of
      adsorption kinetics for the range of conditions above surface coverage of 35%. 

PMID- 24946261
TI  - Photosensitized oxidation of methionine-containing dipeptides. From the
      transients to the final products.
AB  - The Met residue oxidation has been studied for decades. Although many efforts
      have been made on the identification of free radicals, some doubts remain about
      their final fates, i.e., the nature of stable oxidation products. The
      photosensitized oxidation processes of two peptides, methionyl lysine (Met-Lys)
      and lysyl methionine (Lys-Met), were investigated using 3-carboxybenzophenone
      (3CB) as a sensitizer. Therefore, not only the transients were characterized but
      also the final products (by high-performance liquid chromatography and mass
      spectrometry) together with the quantum yields. As for the transients, the sulfur
      radical cations stabilized by a two-center three electron bonds with a nitrogen
      (S...N)(+) were identified in the case of Met-Lys. On the other hand, in Lys-Met,
      the intermolecular (S...S)(+) radical cations were found. The peptide-3CB adduct
      was the only stable product detected and was accompanied neither by sulfoxide
      formation nor by decarboxylation. It shows that both (S...N)(+) and (S...S)(+)
      radicals are converted into the relatively long-lived alpha-(alkylthio)alkyl
      radicals, which add to the 3CB-derived radicals. This addition reaction prevented
      all other oxidation processes such as formation of sulfoxide. The lysine residue
      was totally protected, which may also be of importance in biological processes. 

PMID- 24946263
TI  - Race/ethnic and socioeconomic differences in stress and immune function in The
      National Longitudinal Study of Adolescent Health.
AB  - Stress and immune function may be important mediators of the strong association
      between social factors and health over the life course, but previous studies have
      lacked the data to fully explore these links in a population-based sample. This
      study utilizes data from Waves I-IV of the U.S. National Longitudinal Study of
      Adolescent Health (Add Health) to test the associations of race/ethnicity and
      socioeconomic status (SES) with levels of perceived stress and exposure to
      stressful life events (SLE) among 11,050 adult respondents aged 24-32 in 2008
      2009. We further tested whether race/ethnicity and SES were associated with
      Epstein-Barr Virus (EBV) specific IgG antibodies, an indirect marker of cell
      mediated immune function. Finally, we tested whether measures of stress were
      associated with EBV IgG and whether there was evidence that they explain any
      associations between race/ethnicity, SES and EBV IgG. We found strong
      associations between lower SES and higher levels of perceived stress (OR 2.07,
      95% CI 1.73-2.48 for < high school vs. college or above) and a high level of
      stressful life events (OR 7.47, 95% CI 5.59-9.98 for < high school vs. college or
      above). Blacks had higher odds of a high level of stressful life events compared
      to whites (OR 2.00, 95% CI 1.63-2.47), but not higher perceived stress (OR 1.11,
      95% CI 0.96-1.28). Blacks also had significantly higher EBV levels compared to
      whites (beta = 0.136, p < 0.01), but lower SES was not associated with higher EBV
      IgG. We found no evidence that stressful life events or perceived stress were
      associated with EBV IgG in this sample, and thus did not account for racial
      differences in EBV IgG. These results suggest consistent race/ethnic and SES
      differences in stressful life events, and confirm race/ethnic differences in
      markers of immune function that may have health implications across the life
      course. 

PMID- 24946264
TI  - Deuterohemin-AlaHisLys mitigates the symptoms of rats with non-insulin dependent
      diabetes mellitus by scavenging reactive oxygen species and activating the PI3
      K/AKT signal transduction pathway.
AB  - Damage to pancreatic beta-cells plays an important role in the development of
      type 2 diabetes, and oxidative stress is a likely contributor. In the present
      study, we investigated the effect of deuterohemin-AlaHisLys (DhHP-3), a
      microperoxidase-11 mimic, on rats with non-insulin dependent diabetes mellitus
      and examined the action mechanisms of DhHP-3. The induced hyperglycemia, glucose
      intolerance, and insulin resistance in diabetic rats were associated with
      increased oxidative stress and damage to pancreatic islets. DhHP-3 (3 mg/kg)
      ameliorated hyperglycemia and insulin resistance, protected pancreas islet,
      decreased the content of malondialdehyde, and increased the activity of
      superoxide dismutase in plasma and pancreatic tissue by reducing ROS levels.
      Furthermore, DhHP-3 stimulated the proliferation of INS-1 cells and inhibited
      apoptosis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3
      K/AKT) signaling pathway. Our results demonstrated for the first time that DhHP-3
      decreased blood glucose level in rats with non-insulin dependent diabetes
      mellitus, scavenged reactive oxygen species, activated the PI3-K/AKT signaling
      pathway, and protected pancreatic beta-cells against apoptosis.

PMID- 24946265
TI  - Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage
      in alloxan induced type 2 diabetic mice.
AB  - AIMS: Quercetin is a natural polyphenolic flavonoid and acts as a quencher for
      reactive oxygen species generated by any physical or chemical action. In type 2
      diabetes mellitus (T2DM) the basic characteristic feature is hyperglycemia which
      leads to complications involving oxidative stress. In view of this, the present
      study was conducted to examine the effect of quercetin in T2DM. MAIN METHODS: A
      total of 18 mice were divided into three groups, vis control, diabetic and
      diabetic treated with quercetin. Fasting blood glucose (FBG) levels and anti
      oxidant enzyme activity were assayed. Creatinine, urea, lipid peroxidation, GLUT4
      expression and DNA damage were also measured. KEY FINDINGS: A significant
      decrease in FBG level and liver and kidney marker enzymes was observed in the
      quercetin treated group as compared to the diabetic one. Glutathione, SOD,
      catalase, and glutathione-S-transferase levels were also found to be increased on
      quercetin supplementation. Thiobarbituric acid-reactive substance level was
      decreased while GLUT4 expression levels were increased in the treated group. DNA
      damage was also affected positively by quercetin when subjected with single cell
      alkaline gel electrophoresis. Thus, we may suggest an anti-oxidant potential and
      protective effect of quercetin in T2DM mice. SIGNIFICANCE: From this study, we
      conclude that quercetin ameliorates hyperglycemia and oxidative stress, by
      blunting free radical induced toxicity in T2DM.

PMID- 24946266
TI  - Gait pattern differences in children with unilateral cerebral palsy.
AB  - Children with cerebral palsy (CP) often have atypical body posture patterns and
      abnormal gait patterns resulting from functional strategies to compensate for
      primary anomalies that are directly attributable to damage to the central nervous
      system. Our previous study revealed two different postural patterns in children
      with unilateral CP: (1) a pattern with overloading of the affected body side and
      (2) a pattern with under-loading of the affected side. The purpose of present
      study was to test whether different gait patterns dependent on weight
      distribution between the affected and unaffected body sides could be detected in
      these children. The study included 45 outpatients with unilateral CP and 51
      children with mild scoliosis (reference group). The examination consisted of two
      inter-related parts: paedobarographic measurements of the body mass distribution
      between the body sides and three-dimensional instrumented gait analysis. Using
      cluster analysis based on the Gillette Gait Index (GGI) values, three gait
      patterns were described: a scoliotic gait pattern and two hemiplegic gait
      patterns, corresponding to overloading/under-loading of the hemi-side, which are
      the pro-gravitational gait pattern (PGP) and the anti-gravitational gait pattern
      (AGP), respectively. The results of this study showed that subjects with AGP
      presented a higher degree of deviation from the normal gait than children with
      PGP. This proof that there are differences in the GGI between the AGP and PGP
      could be a starting point to identify kinematic differences between these gaits
      in a follow-up study. 

PMID- 24946267
TI  - Functional balance and gross motor function in children with cerebral palsy.
AB  - AIMS: To compare scores of children with cerebral palsy (CP) at different levels
      of Gross Motor Function Classification System (GMFCS), using the Pediatric
      Balance Scale (PBS) and to assess whether it can be used to predict GMFCS levels
      in children with CP. METHODS: Fifty-eight children with CP levels I-V of GMFCS
      were assessed by PBS and grouped according to their GMFCS level. RESULTS: It was
      observed differences in PBS scores between GMFCS I and II and between GMFCS II
      and III groups. Discriminant analysis indicated a 67% accuracy for the PBS
      instrument in assessing the GMFCS level of children with CP. INTERPRETATION: PBS
      is able to detect differences among GMFCS levels I, II, and III of mild and
      moderate impairment. Accordingly, PBS can be used reliably in clinical practice
      to indicate the motor impairment level of such children. The results enable
      specify the expected tasks that are expected to be accomplished by the children
      in each GMFCS level, contributing with therapeutic planning and monitoring.

PMID- 24946268
TI  - An unavoidable modulation? Sensory attention and human primary motor cortex
      excitability.
AB  - The link between basic physiology and its modulation by cognitive states, such as
      attention, is poorly understood. A significant association becomes apparent when
      patients with movement disorders describe experiences with changing their
      attention focus and the fundamental effect that this has on their motor symptoms.
      Moreover, frequently used mental strategies for treating such patients, e.g. with
      task-specific dystonia, widely lack laboratory-based knowledge about
      physiological mechanisms. In this largely unexplored field, we looked at how the
      locus of attention, when it changed between internal (locus hand) and external
      (visual target), influenced excitability in the primary motor cortex (M1) in
      healthy humans. Intriguingly, both internal and external attention had the
      capacity to change M1 excitability. Both led to a reduced stimulation-induced
      GABA-related inhibition and a change in motor evoked potential size, i.e. an
      overall increased M1 excitability. These previously unreported findings
      indicated: (i) that cognitive state differentially interacted with M1 physiology,
      (ii) that our view of distraction (attention locus shifted towards external or
      distant location), which is used as a prevention or management strategy for use
      dependent motor disorders, is too simple and currently unsupported for clinical
      application, and (iii) the physiological state reached through attention
      modulation represents an alternative explanation for frequently reported
      electrophysiology findings in neuropsychiatric disorders, such as an aberrant
      inhibition. 

PMID- 24946269
TI  - Inhomogeneity of local stiffness in the extracellular matrix scaffold of fibrotic
      mouse lungs.
AB  - Lung disease models are useful to study how cell engraftment, proliferation and
      differentiation are modulated in lung bioengineering. The aim of this work was to
      characterize the local stiffness of decellularized lungs in aged and fibrotic
      mice. Mice (2- and 24-month old; 14 of each) with lung fibrosis (N=20) and
      healthy controls (N=8) were euthanized after 11 days of intratracheal bleomycin
      (fibrosis) or saline (controls) infusion. The lungs were excised, decellularized
      by a conventional detergent-based (sodium-dodecyl sulfate) procedure and slices
      of the acellular lungs were prepared to measure the local stiffness by means of
      atomic force microscopy. The local stiffness of the different sites in acellular
      fibrotic lungs was very inhomogeneous within the lung and increased according to
      the degree of the structural fibrotic lesion. Local stiffness of the acellular
      lungs did not show statistically significant differences caused by age. The group
      of mice most affected by fibrosis exhibited local stiffness that were ~2-fold
      higher than in the control mice: from 27.2+/-1.64 to 64.8+/-7.1kPa in the
      alveolar septa, from 56.6+/-4.6 to 99.9+/-11.7kPa in the visceral pleura, from
      41.1+/-8.0 to 105.2+/-13.6kPa in the tunica adventitia, and from 79.3+/-7.2 to
      146.6+/-28.8kPa in the tunica intima. Since acellular lungs from mice with
      bleomycin-induced fibrosis present considerable micromechanical inhomogeneity,
      this model can be a useful tool to better investigate how different degrees of
      extracellular matrix lesion modulate cell fate in the process of organ
      bioengineering from decellularized lungs. 

PMID- 24946270
TI  - Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated
      chitosan nanoparticles towards colon cancer treatment.
AB  - BACKGROUND: Evaluation of the combinatorial anticancer effects of curcumin/5
      fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs)
      on colon cancer cells and the analysis of pharmacokinetics and biodistribution of
      CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. METHODS: CRC-TCS-NPs/5-FU-TCS-NPs were
      developed by ionic cross-linking. The in vitro combinatorial anticancer effect of
      the nanomedicine was proven by different assays. Further the pharmacokinetics and
      biodistribution analyses were performed in Swiss Albino mouse using HPLC.
      RESULTS: The 5-FU-TCS-NPs (size: 150+/-40nm, zeta potential: +48.2+/-5mV) and CRC
      TCS-NPs (size: 150+/-20nm, zeta potential: +35.7+/-3mV) were proven to be
      compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed
      a sustained release profile over a period of 4 days, where both the systems
      exhibited a higher release in acidic pH. The in vitro combinatorial anticancer
      effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane
      potential and cell cycle analysis measurements confirmed the enhanced anticancer
      effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved
      plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU.
      CONCLUSIONS: To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed
      enhanced anticancer effects on colon cancer cells in vitro and improved the
      bioavailability of the drugs in vivo. GENERAL SIGNIFICANCE: The enhanced
      anticancer effects of combinatorial nanomedicine are advantageous in terms of
      reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy
      and patient compliance of colorectal cancer cases.

PMID- 24946271
TI  - An assessment of two decades of trace metals monitoring in wild mussels from the
      Northwest Atlantic and Cantabrian coastal areas of Spain, 1991-2011.
AB  - Since 1991, the Instituto Espanol de Oceanografia has monitored the
      concentrations of trace metals in wild mussels from the north (Cantabrian Sea)
      and northwest (Atlantic) coasts of Spain to define geographical distributions and
      temporal trends. While Cu, Zn and As concentrations presented fairly uniform
      geographical distributions, Hg and Pb concentrations were higher in mussels from
      the Cantabrian sea region as a result of historical anthropogenic activities. Cd,
      on the other hand, appeared to be more affected by natural processes on the
      northwest Atlantic coast (i.e., upwelling) than by human activity. Approximately
      70% of the paired observations showed downward trends, 50% of these significant,
      with time. An improvement in environmental conditions along the northern coasts
      of Spain is evident despite that some metal levels resulted above the Background
      Assessment Concentrations given by OSPAR to assess potentially harmful
      occurrences. 

PMID- 24946272
TI  - Current developments in activity-based protein profiling.
AB  - Activity-based protein profiling (ABPP) has emerged as a powerful strategy to
      study the activity of enzymes in complex proteomes. The aim of ABPP is to
      selectively visualize only the active forms of particular enzymes using chemical
      probes termed activity-based probes (ABPs). These probes are directed to the
      active site of a particular target protein (or protein family) where they react
      in a mechanism-based manner with an active site residue. This results in the
      selective labeling of only the catalytically active form of the enzyme, usually
      in a covalent manner. Besides the monitoring of a specific enzymatic activity,
      ABPP strategies have also been used to identify and characterize (unknown)
      protein functions, to study up- and down-regulation of enzymatic activity in
      various disease states, to discover and evaluate putative new enzyme inhibitors,
      and to identify the protein targets of covalently binding natural products. In
      this Topical Review we will provide a brief overview of some of the recent
      developments in the field of ABPP. 

PMID- 24946273
TI  - Component position alignment with patient-specific jigs in total knee
      arthroplasty.
AB  - BACKGROUND: The failure to restore mechanical alignment and appropriate
      rotational axis intraoperatively has been described as one of the most common
      causes of implant failure in total knee arthroplasty (TKA). Both conventional and
      computer-assisted TKA have their limitations. Patient-specific jigs (PSJ) offer a
      possible alternative method for TKA. The aim of this study was to investigate if
      the use of PSJ offers reproducible and accurate orientation of the components in
      TKA compared with conventional and computer-assisted surgery. METHODS: We
      conducted a prospective case series looking at 261 consecutive patients
      undergoing TKA for osteoarthritis using the Signature Patient Specific System
      (Biomet, North Ryde, NSW, Australia). Each patient underwent a preoperative
      magnetic resonance imaging for planning. Using a computer software program,
      specialized femoral and tibial pin placement jigs were generated. Post-operative
      femoral and tibial component alignment was measured using computed tomography.
      RESULTS: Of patients, 96.2% achieved femoral rotational alignment +/-3 degrees of
      the transepicondylar axis. Tibial coronal alignment showed 92.7% of cases were 90
      +/- 3 degrees to the tibial medullary axis. Implant measurements of the posterior
      tibial slope demonstrated 76.6% of cases were within our accepted 0 to 7 degrees
      slope and 81.2% of patients had an overall mechanical axis within +/-3 degrees of
      neutral. We also recorded femoral coronal alignment of the last 98 patients of
      our group and found that 99% were within 90 +/- 3 degrees. CONCLUSION: PSJ for
      TKA shows good accuracy in alignment when compared with conventional TKA.
      However, improvements in the development of the tibial alignment cutting guides
      will aid in further increasing its overall accuracy and reproducibility.

PMID- 24946275
TI  - Patients' concern about their medicine after a generic switch: a combined cross
      sectional questionnaire and register study.
AB  - PURPOSE: This study aims to investigate the possible association between
      patients' concerns about their medicine and generic switch. METHODS: Cross
      sectional survey was carried out comprising responses from 2217 randomly selected
      persons aged 20 years or older and living in the Region of Southern Denmark, who
      had redeemed generically substitutable drugs in September 2008. For each patient,
      we focused on the purchase of one generically substitutable drug (index drug). We
      applied the specific concerns subscale from the Beliefs about Medicine
      Questionnaire (BMQ) to analyse lack of confidence in treatment. We also included
      general beliefs about medicine (BMQ), views on generic medicine and confidence in
      the health-care system. The information about the patients' generic switch was
      obtained from a prescription database and not provided by the patients. Data were
      analysed using linear regression. RESULTS: No statistically significant
      associations were found between concerns about the index medicine and the generic
      switch (-0.02 95% CI: -0.10; 0.05). Viewing medicines as harmful in general was
      associated with increased concerns (BMQ general harm: 0.39 95% CI: 0.30; 0.47 and
      BMQ general overuse: 0.28 95% CI: 0.20; 0.35). Patients having high confidence in
      the health-care system showed less concern (-0.16 95% CI: -0.27; -0.06).
      CONCLUSION: This study showed that for all three drug categories investigated,
      the patients who experienced a generic switch did not have more concerns about
      their index medicine than patients who did not switch.

PMID- 24946274
TI  - Divergent modulation of Src-family kinase regulatory interactions with ATP
      competitive inhibitors.
AB  - Multidomain protein kinases, central controllers of signal transduction, use
      regulatory domains to modulate catalytic activity in a complex cellular
      environment. Additionally, these domains regulate noncatalytic functions,
      including cellular localization and protein-protein interactions. Src-family
      kinases (SFKs) are promising therapeutic targets for a number of diseases and are
      an excellent model for studying the regulation of multidomain kinases. Here, we
      demonstrate that the regulatory domains of the SFKs Src and Hck are divergently
      affected by ligands that stabilize two distinct inactive ATP-binding site
      conformations. Conformation-selective, ATP-competitive inhibitors differentially
      modulate the ability of the SH3 and SH2 domains of Src and Hck to engage in
      intermolecular interactions and the ability of the kinase-inhibitor complex to
      undergo post-translational modification by effector enzymes. This surprising
      divergence in regulatory domain behavior by two classes of inhibitors that each
      stabilize inactive ATP-binding site conformations is found to occur through
      perturbation or stabilization of the alphaC helix. These studies provide insight
      into how conformation-selective, ATP-competitive inhibitors can be designed to
      modulate domain interactions and post-translational modifications distal to the
      ATP-binding site of kinases. 

PMID- 24946276
TI  - Cyclodextrin polymers as highly effective adsorbents for removal and recovery of
      polychlorobiphenyl (PCB) contaminants in insulating oil.
AB  - A total of 179 countries (parties) ratified the Stockholm Convention on
      persistent organic pollutants (POPs) and agreed to destroy polychlorobiphenyls
      (PCBs) and develop a sound management plan by 2028. Currently, still 3 million
      tons of PCB-contaminated oil and equipment need to be managed under the Stockholm
      Convention. Thus, the development of a facile and environmentally benign method
      to treat large amounts of oil stockpiles contaminated with PCBs is a crucial
      subject. Herein, we report that cyclodextrin (CD) polymers, which are easily
      prepared by cross-linking the renewable cyclic oligosaccharide gamma-cyclodextrin
      (gamma-CD) with dibasic acid dichlorides, are a new selective and powerful
      adsorbent to remove PCB contaminants in oil. When PCB (100 ppm)-contaminated oil
      was passed through a column packed with the terephthaloyl-cross-linked gamma-CD
      polymer (TP-gamma-CD polymer) at 80-110  degrees C, the PCB contaminants were
      completely removed from the oil. Additionally, methyl esterification of the free
      carboxylic groups of the TP-gamma-CD polymer enabled the complete recovery of the
      PCBs adsorbed on the polymer (with >99.9% recovery efficiency) by simply washing
      with acetone. The methyl-esterified TP-gamma-CD polymer could be recycled at
      least 10 times for PCB adsorption without any loss in the adsorption capability.
      These results revealed that the gamma-CD polymers can function as highly
      effective and powerful adsorbents for the removal and recovery of PCBs from PCB
      contaminated oil and, thus, significantly contribute to the protection of the
      global environment. 

PMID- 24946277
TI  - Metalloproteinase inhibition prevents inhibitory synapse reorganization and
      seizure genesis.
AB  - The integrity and stability of interneurons in a cortical network are essential
      for proper network function. Loss of interneuron synaptic stability and precise
      organization can lead to disruptions in the excitation/inhibition balance, a
      characteristic of epilepsy. This study aimed to identify alterations to the
      GABAergic interneuron network in the piriform cortex (PC: a cortical area
      believed to be involved in the development of seizures) after kindling-induced
      seizures. Immunohistochemistry was used to mark perineuronal nets (PNNs:
      structures in the extracellular matrix that provide synaptic stability and
      restrict reorganization of inhibitory interneurons) and interneuron nerve
      terminals in control and kindled tissues. We found that PNNs were significantly
      decreased around parvalbumin-positive interneurons after the induction of
      experimental epilepsy. Additionally, we found layer-specific increases in GABA
      release sites originating from calbindin, calretinin, and parvalbumin
      interneurons, implying that there is a re-wiring of the interneuronal network.
      This increase in release sites was matched by an increase in GABAergic post
      synaptic densities. We hypothesized that the breakdown of the PNN could be due to
      the activity of matrix metalloproteinases (MMP) and that the prevention of PNN
      breakdown may reduce the rewiring of interneuronal circuits and suppress
      seizures. To test this hypothesis we employed doxycycline, a broad spectrum MMP
      inhibitor, to stabilize PNNs in kindled rats. We found that doxycycline prevented
      PNN breakdown, re-organization of the inhibitory innervation, and seizure
      genesis. Our observations indicate that PNN degradation may be necessary for the
      development of seizures by facilitating interneuron plasticity and increased
      GABAergic activity. 

PMID- 24946278
TI  - High-resolution measurements of the multilayer ultra-structure of articular
      cartilage and their translational potential.
AB  - Current musculoskeletal imaging techniques usually target the macro-morphology of
      articular cartilage or use histological analysis. These techniques are able to
      reveal advanced osteoarthritic changes in articular cartilage but fail to give
      detailed information to distinguish early osteoarthritis from healthy cartilage,
      and this necessitates high-resolution imaging techniques measuring cells and the
      extracellular matrix within the multilayer structure of articular cartilage. This
      review provides a comprehensive exploration of the cellular components and
      extracellular matrix of articular cartilage as well as high-resolution imaging
      techniques, including magnetic resonance image, electron microscopy, confocal
      laser scanning microscopy, second harmonic generation microscopy, and laser
      scanning confocal arthroscopy, in the measurement of multilayer ultra-structures
      of articular cartilage. This review also provides an overview for micro
      structural analysis of the main components of normal or osteoarthritic cartilage
      and discusses the potential and challenges associated with developing non
      invasive high-resolution imaging techniques for both research and clinical
      diagnosis of early to late osteoarthritis.

PMID- 24946280
TI  - Sustained virological response with telaprevir in 1,078 patients with advanced
      hepatitis C: the international telaprevir access program.
AB  - BACKGROUND & AIMS: There is little information regarding the extent to which
      difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus
      genotype-1 (HCV-1) can successfully and safely be treated with triple therapy
      with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the
      TVR early access program HEP3002 we aimed to explore treatment safety and
      efficacy, and identify predictors of sustained virological response at week 24
      (SVR24). METHODS: 1078 patients with bridging fibrosis (n=552) or cirrhosis
      (n=526) diagnosed by either liver biopsy or non-invasive markers, with
      compensated bone marrow (neutrophils >1500/mm(3), Hb >12/13 g/dl) and liver
      function (Albumin >3.3g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks,
      followed by a PR tail according to label. RESULTS: Overall, 614 (57%) achieved
      SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment
      naive patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139
      partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The
      SVR24 rate to response-guided therapy (24 weeks treatment duration if
      undetectable viremia at weeks 4 and 12) was 84% in 222 naive/relapser F3
      patients. Independent predictors of response were: (A) F3 (odds ratio (OR)=1.51,
      95% CI 1.31-2.00, p=0.005), (B) subtype 1b (OR=1.63, 95% CI 1.18-2.24, p=0.0029),
      (C) alpha-fetoprotein <10 ng/ml (OR=2.50, 95% CI 1.87-3.36, p<0.0001) and (D) any
      prior response other than null (OR=3.29, 95% CI 2.40-4.52, p<0.0001). SVR24 rose
      for patients who had more of these predictive factors: 6/32 (19%) for none,
      38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%)
      for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced
      by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died
      during the PR tail. CONCLUSIONS: Naive and experienced patients with advanced
      fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver
      function, can effectively and safely be treated by TVR triple therapy. Baseline
      predictors of outcome have been identified to optimize pre-treatment counselling.

PMID- 24946279
TI  - ASMase regulates autophagy and lysosomal membrane permeabilization and its
      inhibition prevents early stage non-alcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: Acid sphingomyelinase (ASMase) is activated in non-alcoholic
      steatohepatitis (NASH). However, the contribution of ASMase to NASH is poorly
      understood and limited to hepatic steatosis and glucose metabolism. Here we
      examined the role of ASMase in high fat diet (HFD)-induced NASH. METHODS:
      Autophagy, endoplasmic reticulum (ER) stress and lysosomal membrane
      permeabilization (LMP) were determined in ASMase(-/-) mice fed a HFD. The impact
      of pharmacological ASMase inhibition on NASH was analyzed in wild type mice fed a
      HFD. RESULTS: ASMase deficiency determined resistance to hepatic steatosis
      mediated by a HFD or methionine-choline deficient diet. ASMase(-/-) mice were
      resistant to HFD-induced hepatic ER stress, but sensitive to tunicamycin-mediated
      ER stress, indicating selectivity in the resistance of ASMase(-/-) mice to ER
      stress and steatosis. Autophagic flux, determined in the presence of rapamycin
      and/or chloroquine, was lower in primary mouse hepatocytes (PMH) from ASMase(-/-)
      mice and accompanied by increased p62 levels, suggesting autophagic impairment.
      Moreover, autophagy suppression by chloroquine and brefeldin A caused ER stress
      in PMH from ASMase(+/+) mice but not in ASMase(-/-) mice. ASMase(-/-) PMH
      exhibited increased lysosomal cholesterol loading, decreased LMP and apoptosis
      resistance induced by O-methyl-serine dodecylamide hydrochloride or palmitic
      acid, effects that were reversed by decreasing cholesterol levels by oxysterol 25
      hydroxycholesterol. In vivo pharmacological ASMase inhibition by amitriptyline, a
      widely used tricyclic antidepressant, protected wild type mice against HFD
      induced hepatic steatosis, fibrosis, and liver damage, effects indicative of
      early-stage NASH. CONCLUSIONS: These findings underscore a critical role for
      ASMase in diet-induced NASH and suggest the potential of amitriptyline as a
      treatment for patients with NASH.

PMID- 24946282
TI  - A common polymorphism in the NCAN gene is associated with hepatocellular
      carcinoma in alcoholic liver disease.
AB  - BACKGROUND & AIMS: The genetic background of alcoholic liver diseases and their
      complications are increasingly recognized. A common polymorphism in the neurocan
      (NCAN) gene, which is known to be expressed in neuronal tissue, has been
      identified as a risk factor for non-alcoholic fatty liver disease (NAFLD). We
      investigated if this polymorphism may also be related to alcoholic liver disease
      (ALD) and hepatocellular carcinoma (HCC). METHODS: We analysed the distribution
      of the NCAN rs2228603 genotypes in 356 patients with alcoholic liver cirrhosis,
      126 patients with alcoholic HCC, 382 persons with alcohol abuse without liver
      damage, 362 healthy controls and in 171 patients with hepatitis C virus (HCV)
      associated HCC. Furthermore, a validation cohort of 229 patients with alcoholic
      cirrhosis (83 with HCC) was analysed. The genotypes were determined by LightSNiP
      assays. The expression of NCAN was studied by RT-PCR and immunofluorescence
      microscopy. RESULTS: The frequency of the NCAN rs2228603 T allele was
      significantly increased in patients with HCC due to ALD (15.1%) compared to
      alcoholic cirrhosis without HCC (9.3%), alcoholic controls (7.2%), healthy
      controls (7.9%), and HCV associated HCC (9.1%). This finding was confirmed in the
      validation cohort (15.7% vs. 6.8%, OR=2.53; 95%CI: 1.36-4.68; p=0.0025) and by
      multivariate analysis (OR=1.840; 95%CI: 1.22-2.78; p=0.004 for carriage of the
      rs2228603 T allele). In addition, we identified and localised NCAN expression in
      human liver. CONCLUSIONS: NCAN is not only expressed in neuronal tissue, but also
      in the liver. Its rs2228603 polymorphism is a risk factor for HCC in ALD, but not
      in HCV infection.

PMID- 24946281
TI  - Protective role of HO-1 and carbon monoxide in ethanol-induced hepatocyte cell
      death and liver injury in mice.
AB  - BACKGROUND & AIMS: Alcoholic liver disease is associated with inflammation and
      cell death. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with anti
      apoptotic and anti-inflammatory properties. Here we tested the hypothesis that
      induction of HO-1 or treatment with a carbon monoxide releasing molecule (CORM)
      during chronic ethanol exposure protects and/or reverses ethanol-induced liver
      injury. METHODS: Female C57BL/6J mice were allowed free access to a complete
      liquid diet containing ethanol or to pair-fed control diets for 25days. Mice were
      treated with cobalt protoporphyrin (CoPP) to induce HO-1 expression during
      ethanol feeding or once liver injury had been established. Mice were also treated
      with CORM-A1, a CO-releasing molecule (CORM), after ethanol-induced liver injury
      was established. The impact of HO-1 induction on ethanol-induced cell death was
      investigated in primary cultures of hepatocytes. RESULTS: Induction of HO-1
      during or after ethanol feeding, as well as treatment with CORM-A1, ameliorated
      ethanol-induced increases in AST and expression of mRNAs for inflammatory
      cytokines. Treatment with CoPP or CORM-A1 also reduced hepatocyte cell death,
      indicated by decreased accumulation of CK18 cleavage products and reduced RIP3
      expression in hepatocytes. Exposure of primary hepatocyte cultures to ethanol
      increased their sensitivity to TNFalpha-induced cell death; this response was
      attenuated by necrostatin-1, an inhibitor of necroptosis, but not by caspase
      inhibitors. Induction of HO-1 with CoPP or CORM-3 treatment normalized the
      sensitivity of hepatocytes to TNFalpha-induced cell death after ethanol exposure.
      CONCLUSIONS: Therapeutic strategies to increase HO-1 and/or modulate CO
      availability ameliorated chronic ethanol-induced liver injury in mice, at least
      in part by decreasing hepatocellular death.

PMID- 24946285
TI  - Proteomics of citrullination in cardiovascular disease.
AB  - Citrullination is an enzymatic posttranslational modification (PTM), which has
      become a topic of recent research due to its involvement in various physiologic
      and pathologic processes. This review will focus primarily on the cardiovascular
      pathology associated to date with citrullination, including myocardial
      citrullination as well as the potential role of citrullination in atherosclerosis
      as a driver inflammation, especially in patients with rheumatoid arthritis (RA).
      There is extensive citrullination within normal and RA myocardium as well as the
      atherosclerotic plaque; and increased levels of antibodies to citrullinated
      proteins have been associated with increased cardiovascular burden in patients
      with RA. Given robust citrullination in both RA as well as non-RA patients, there
      also exists the potential for protein citrullination to contribute to
      cardiovascular pathology in the general population. However, to investigate this
      possibility will require development of improved biochemical and proteomic tools
      for the study of protein citrullination. The remainder of this review will
      discuss current and developing methodologies to study protein citrullination and
      discuss their applicability for the analysis of complex samples. The ability to
      identify and quantify citrullinated protein is a key to understanding the role of
      this PTM. Methodologies and limitations of current technology for the
      identification of citrullination are discussed.

PMID- 24946284
TI  - Inhibition of fibronectin deposition improves experimental liver fibrosis.
AB  - BACKGROUND & AIMS: Common pathogenic steps in liver fibrosis are inflammation and
      accumulation of extracellular matrix proteins including collagen, which lead to
      disruption of tissue microarchitecture and liver dysfunction. Adequate
      fibronectin fibril formation is required for collagen matrix deposition in
      several cell types in vitro. We therefore hypothesized that preventing
      fibronectin fibril assembly will result in decreased collagen matrix
      accumulation, and hence diminish liver injury associated with fibrosis. METHODS:
      In vitro studies on hepatic stellate cells and in vivo studies in mice were
      performed. RESULTS: In vitro studies on hepatic stellate cells confirmed that a
      fibronectin assembly inhibitor, pUR4 diminishes the amount of both fibronectin
      and collagen, accumulating in the extracellular matrix, without affecting their
      production. Induction of fibrosis using CCl4 or DMN was therefore combined with
      pUR4-treatment. pUR4 normalized the amount of fibrotic tissue that accumulated
      with injury, and improved liver function. Specifically, pUR4-treatment decreased
      collagen accumulation, without changing its mRNA expression. Most interestingly,
      we did not detect any changes in Kupffer cell numbers (F4/80+) or alpha-smooth
      muscle actin expressing hepatic stellate cell numbers. Further, there was no
      impact on TGF-beta or TNF-alpha. Thus, in line with the in vitro findings,
      decreased fibrosis is due to inhibition of matrix accumulation and not a direct
      effect on these cells. CONCLUSIONS: In summary, a peptide that blocks fibronectin
      deposition results in decreased collagen accumulation and improved liver function
      during liver fibrogenesis. Thus, fibronectin matrix modulation offers a
      therapeutic benefit in preclinical models of liver fibrosis.

PMID- 24946286
TI  - Editorial.

PMID- 24946287
TI  - Do drugs have a place in the treatment of eating disorders in adolescence?
AB  - This paper reviews the literature on drug treatment of eating disorders in
      adolescence. No well-controlled psychopharmacological studies specifically of
      adolescent patients with eating disorders have been performed. Therefore, the
      evidence for rational treatment guidelines is extremely limited. More
      psychopharmacological studies - especially SSRI trials - of adolescents with
      eating disorders are needed before general clinical recommendations can be
      issued. Cyproheptadine appears to be a safe and interesting drug that should be
      explored further, particularly in severely restricting patients with anorexia
      nervosa (AN). The use of zinc supplement in the treatment of AN also requires
      further study. 

PMID- 24946283
TI  - OATP1B3 expression is strongly associated with Wnt/beta-catenin signalling and
      represents the transporter of gadoxetic acid in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: In the current era of emerging molecular targeted drugs, it is
      necessary to identify before treatment the specific subclass to which a tumour
      belongs. Gadoxetic acid is a liver-specific contrast agent that is preferentially
      taken up by hepatocytes. Therefore, gadoxetic acid-enhanced magnetic resonance
      imaging (EOB-MRI) should provide precise molecular information about
      hepatocellular carcinomas (HCCs). The aim of this study was to investigate the
      transporters of gadoxetic acid in HCC comprehensively and to analyse the
      molecular regulatory mechanism of such transporters. METHODS: Expression levels
      of transporters, transcriptional factors and Wnt target genes in clinical samples
      were examined by quantitative real-time reverse transcription polymerase chain
      reaction and immunohistochemistry. LiCl treatment of the HCC cell line KYN-2 was
      conducted in vitro to assess the effects of Wnt signalling activity. RESULTS:
      Comprehensive analyses of transporter mRNAs and protein expressions revealed that
      the organic anion transporting polypeptide 1B3 (OATP1B3) had the strongest
      correlation with tumour enhancement in hepatobiliary-phase images of EOB-MRI.
      Association analysis with OATP1B3 expression revealed significant correlation
      with the expression of Wnt/beta-catenin target genes. Further, LiCl treatment
      induced OATP1B3 mRNA expression in KYN-2 cells, indicating a strong association
      between OATP1B3 expression and Wnt/beta-catenin signalling. The sensitivity and
      specificity to predict Wnt/beta-catenin-activated HCC using tumour enhancement in
      EOB-MRI were 78.9% and 81.7%, respectively. CONCLUSIONS: OATP1B3 was confirmed as
      the most important transporter mediating HCC enhancement in EOB-MRI. OATP1B3
      expression showed a strong association with the expression of Wnt/beta-catenin
      target genes, therefore, OATP1B3-upregulated HCC likely represents a specific
      subclass of Wnt/beta-catenin-activated HCC.

PMID- 24946288
TI  - The long term effects of childhood sexual abuse: rationale for and experience of
      pharmacotherapy with nefazodone.
AB  - Studies estimate that 1 in 6 women and 1 in 10 men experience childhood sexual
      abuse (CSA). Whilst ill-health is not an inevitable consequence, approximately
      20% of victims go on to have serious long-term pathology. This is reflected in an
      excess incidence of CSA survivors in problem populations, be they medical,
      forensic or psychiatric. Four groups of research studies suggest that PTSD
      related mechanisms might be a major mediating factor in the development of
      symptoms: 1. There is high incidence of PTSD following sexual trauma; 2.
      Psychometric studies show evidence of impaired limbic functions; 3. There is
      evidence of neuroendocrine disturbances similar to those seen in war veterans
      with PTSD; 4. MRI studies show evidence of hippocampal atrophy. There is a
      growing database of studies showing that drugs that act as seroionergic
      modulators are effective in the treatment of PTSD. Drugs such as nefazodone which
      block 5HT2 receptors and inhibit the uptake of serotonin may be of particular
      value. Studies suggest that trauma-related issues are not always addressed in
      patients with a history of abuse. Given the problems posed, there is a need to
      review their treatment in the light of emergent knowledge. Further research is
      needed to validate these findings. 

PMID- 24946289
TI  - Mania and bipolar disorder: Current concepts on assessment, diagnosis and
      management.
AB  - Mania is a common psychiatric syndrome characterized by pathological mood
      elevation, grandiose thinking and motor overactivity. Although current consensus
      upholds a true distinction between unipolar depression and bipolar disorders, the
      distinction between various bipolar sub-categories is still a matter for debate,
      as is the exact distinction between schizophrenia and mania. Most cases are
      functional in origin but many organic causes have been identified as well as
      iatrogenic causes from prescribed medication, particularly in susceptible
      individuals. The underlying aetiology is still poorly understood, although a
      number of biochemical abnormalities have recently been identified, and the
      evidence for a genetic role is strong. Its prevalence is universal, with some
      differences between gender and ethnicity reported, and it displays marked Axis I
      and II comorbidity. Treatment, both acute and long term, still relies on various
      traditional combinations of neuroleptics, benzodiazepines and mood stabilisers,
      particularly Lithium, which now appears to be less effective than previously
      thought and a shift towards using other mood stabilisers from the anticonvulsant
      class is now apparent. The exact role for psychological treatment remains unclear
      with more research required. Good medical management includes; adequate
      treatment, physical and laboratory investigations, dedicated follow-up and
      supervision by hospital psychiatrists and community-based care agencies. 

PMID- 24946290
TI  - Therapeutic strategies for patients with social phobia.
AB  - Social phobia is a serious condition in the range of anxiety disorders which,
      until quite recently, has not been given due attention in research. In this paper
      we compare existing studies and follow-up results of behaviour therapy and
      pharmacotherapy. We have endeavoured to work out an effective therapy for this
      serious condition. Apart from psychological education as a basic therapeutic
      element, the use of effective drugs promises to yield good results, especially in
      conjunction with behaviour therapy, including training in social skills,
      cognitive therapy and exposure therapy. Whichever form of treatment is chosen
      depends on the patient's preference and the availability of services. If the
      patient does not respond, the possible causes should be examined thoroughly and
      new types of treatment considered. A combination of behaviour and drug treatments
      might be provided for special groups. 

PMID- 24946291
TI  - Long-term outcome and mortality of treated versus untreated bipolar and depressed
      patients: A preliminary report.
AB  - The mortality of patients with mood disorders is elevated as a consequence not
      only of suicides and accidents but also of cardiovascular and other diseases -
      for instance, hypothyroidism and hyperthyroidism. Long-term medication can reduce
      suicides by two-thirds and can probably reduce non-suicidal mortality also. This
      long-term study of 406 hospital admissions recruited between 1959 and 1963 and
      followed up until 1991 suggests that not only lithium (as reported in the
      literature), but also neuroleptics and antidepressants may have such beneficial
      effects. 

PMID- 24946292
TI  - Drug information for the mentally ill: A randomized controlled trial.
AB  - Drugs play a significant role in maintaining the health of the mentally ill Lack
      of information is known to be one of the chief reasons for patients' failure to
      adhere to prescribed regimens. This study was designed to evaluate the impact of
      drug information leaflets for mentally ill patients on knowledge and satisfaction
      concerning psychotropic drug therapy. We conducted a randomized controlled trial
      of 249 adult general psychiatry patients (124 inpatients and 125 community
      patients), half assigned to the invervention (i.e., patient information leaflets;
      these patients also received the usual information) (n = 120) and half receiving
      the usual information only (n = 129). The assessments were made using a semi
      structured questionnaire. The mean total knowledge score was significantly higher
      with intervention in both acute and community patients. Analysis of individual
      aspects of knowledge showed a marked lack of knowledge in the areas of side
      effects and precautions, which improved significantly with intervention. Patients
      in the community showed a greater awareness of their drug therapy than did
      inpatients. Improvement in knowledge was evident in all diagnostic groups. There
      was no significant relationship with age, sex, level of education and number of
      drugs. Overall, 60% of controls and 79% of leaflet patients were satisfied with
      their drug information. Patient information leaflets provided a useful source of
      reference for the patients and the carers. 

PMID- 24946293
TI  - Influence of antipsychotic profile on cost of treatment of schizophrenia: A
      decision analysis approach.
AB  - Schizophrenia affects around 1% of the population but accounts for a much larger
      proportion of healthcare costs. New atypical antipsychotics are perceived as
      expensive because of higher drug costs, even though such drug costs account for
      only a small percentage of the total cost of care. However, if these agents
      reduce other types of treatment costs they could prove to be highly cost
      effective. This paper presents a health economic model for the treatment of an
      acute episode of chronic schizophrenia and its subsequent control through
      maintenance treatment. Simulation experiments, using cost data reported for
      England, indicate that the most important treatment cost is care setting:
      treatments enabling patients to move from expensive inpatient and sheltered
      accommodation to less expensive settings represent the largest potential cost
      saving. Atypical antipsychotics with improved efficacy in negative symptoms
      and/or cognitive function may facilitate this and thus lead to substantial
      savings. Enhanced efficacy in positive symptoms, and improvements in compliance
      and relapse rates also have an influence on the cost of treating schizophrenia.
      Model predictions suggest that reported clinical profiles of atypical
      antipsychotics could lead to significant savings and large improvements in
      effectiveness over conventional therapy. Prospective studies are required to
      confirm these findings. 

PMID- 24946295
TI  - The treatment of sleep disorders in people with learning disabilities using light
      therapy.
AB  - Light therapy is a recognized treatment for sleep phase disorders in the general
      population. Exposure to natural light can be a powerful means of correcting
      people's sleep/wake pattern. Although sleep problems in the learning-disabled
      population are common, research is limited. Light therapy has not to our
      knowledge been studied in this population. We report the case of a man with
      profound learning disabilities and poor visual acuity who was successfully
      treated with natural light for chronic sleep disturbance. Light therapy is safe,
      cheap and relatively easy to carry out. It may prove helpful in subjects with
      learning disabilities who have sleep problems, even if they do not fulfill the
      criteria for a particular sleep disorder. 

PMID- 24946294
TI  - Perceived needs in chronic schizophrenia.
AB  - Recent approaches to needs assessment involve patients themselves in the process,
      but little is known about the effects of mental illness on their ability to judge
      their own needs accurately. The needs of 30 subjects with schizophrenia in
      rehabilitation units were assessed in 19 different domains, by obtaining the
      views both of the subjects and their keyworkers. For each, the number of domains
      in which the subjects underestimated their level of need compared with the level
      estimated by their keyworker was calculated, to give a 'disparity score'.
      Disparity scores were positively correlated with severity of negative symptoms (r
      = 0.36; P = 0.048) but only nonsignificantly negatively correlated with insight
      (r = 0.31; P = 0.098). For the domains of alcohol misuse (P = 0.043) and quality
      of social life (P = 0.0005), subjects who underestimated their needs had poorer
      insight than those who did not do so. Subjects did not necessarily deny their
      need for help with psychosocial handicaps even if they denied having a mental
      illness or requiring medication. For the areas of alcohol misuse and social
      contact, however, additional objective means of assessment may be advisable in
      patients with poor insight into their illness. The effects of negative symptoms
      should also be taken into account when assessing needs collaboratively. 

PMID- 24946296
TI  - Cyproterone acetate and striae.

PMID- 24946299
TI  - Construction of acylhydrazidate-extended metal-organic frameworks.
AB  - Under hydrothermal conditions, the reactions of Ba(2+)/Zn(2+), aromatic
      polycarboxylic acids and N2H4 with or without oxalic acid were carried out,
      affording four new acylhydrazidate-extended metal-organic frameworks (MOFs)
      [Ba(pmdh)] (pmdh = pyromellitdihydrazidate) 1, [Ba(sdpth)(H2O)2].0.5H2O (sdpth =
      4,4'-sulfoyldiphthalhydrazidate) 2, [Ba2(cpth)2(H2O)2] (cpth = 4
      carboxylphthalhydrazidate) 3 and [Zn2(pdh)2(ox)].H2O (ox = oxalate, pdh =
      pyridine-2,3-dicarboxylhydrazidate) 4. The acylhydrazidate molecules pmdh, sdpth,
      cpth and pdh in compounds 1-4 derived from the hydrothermal in situ acylation of
      N2H4 with aromatic polycarboxylic acids. X-ray single-crystal diffraction
      analysis revealed that (i) in compound 1, the pmdh I molecules link the Ba(2+)
      ions into a two-dimensional (2D) layer with a (4,4) topology, and then the pmdh
      II molecules extend these layers into a three-dimensional (3D) network; (ii) in
      compound 2, the sdpth molecules link the Ba(2+) ions to form a one-dimensional
      (1D) square tube. Interestingly, the tubes are further linked into a 3D
      supramolecular network via the N-H...O interactions, creating synchronously big
      channels; (iii) in compound 3, the cpth I molecules link the Ba1 ions into a 3D
      network with a (10,3) topology. Ba2 and cpth II are distributed on the channels;
      (iv) in compound 4, Zn(2+) and pdh aggregate to form two types of Zn4(pdh)4
      clusters. The ox molecules act as the secondary linkers, extending the Zn4(pdh)4
      secondary building units (SBUs) into a 3D network with a 6(6) topology. The
      photoluminescence analysis indicates that compounds 3 and 4 emit green light with
      maxima at 495 nm for 3 (lambda(ex) = 397 nm), and 522 nm for 4 (lambda(ex) = 395
      nm), respectively. At 77 K, the activated 2 and 4 can adsorb N2 in amounts of
      58.31 cm(3) g(-1) for 2 and 38.38 cm(3) g(-1) for 4, respectively.

PMID- 24946301
TI  - Sensory incongruence leading to hand disownership modulates somatosensory
      cortical processing.
AB  - The sense of body ownership is based on integration of multimodal sensory
      information, including tactile sensation, proprioception, and vision. Distorted
      body ownership contributes to the development of chronic pain syndromes and
      possibly symptoms of psychiatric disease. However, the effects of disownership on
      cortical processing of somatosensory information are unknown. In the present
      study, we created a "disownership" condition in healthy individuals by
      manipulating the visual information indicating the location of the subject's own
      left hand using a mirror box and examined the influence of this disownership on
      cortical responses to electrical stimulation of the left index finger using
      magnetoencephalography (MEG). The event-related magnetic field in the right
      primary somatosensory cortex at approximately 50 msec (M50) after stimulus was
      enhanced under the disownership condition. The present results suggest that M50
      reflects a cortical incongruence detection mechanism involving integration of
      sensory inputs from visual and proprioceptive systems. This signal may be
      valuable for future studies of the mechanisms underlying sense of body ownership
      and the role that disrupted sense of ownership has in neurological disease. 

PMID- 24946302
TI  - The left inferior frontal gyrus is crucial for reading the mind in the eyes:
      brain lesion evidence.
AB  - Deficit in the ability to understand and predict the mental states of others is
      one of the central features of traumatic brain injury (TBI), leading to problems
      in social-daily life such as social withdrawal and the inability to maintain work
      or family relationships. Although several functional neuroimaging studies have
      identified a widely distributed brain network involved in the Reading the Mind in
      the Eyes Test (RMET), the necessary brain regions engaged in this capacity are
      still heavily debated. In this study, we combined the RMET with a whole-brain
      voxel-based lesion symptom mapping (VLSM) approach to identify brain regions
      necessary for adequate RMET performance in a large sample of patients with
      penetrating TBI (pTBI). Our results revealed that pTBI patients performed worse
      on the RMET compared to non-head injured controls, and impaired RMET performance
      was associated with lesions in the left inferior frontal gyrus (IFG). Our
      findings suggest that the left IFG is a key region in reading the mind in the
      eyes, probably involved in a more general impairment of a semantic working memory
      system that facilitates reasoning about what others are feeling and thinking as
      expressed by the eyes. 

PMID- 24946303
TI  - Computational modeling of drug distribution in the posterior segment of the eye:
      effects of device variables and positions.
AB  - A computational model was developed to simulate drug distribution in the
      posterior segment of the eye after intravitreal injection and ocular
      implantation. The effects of important factors in intravitreal injection such as
      injection time, needle gauge and needle angle on the ocular drug distribution
      were studied. Also, the influences of the position and the type of implant on the
      concentration profile in the posterior segment were investigated. Computational
      Fluid Dynamics (CFD) calculations were conducted to describe the 3D convective
      diffusive transport. The geometrical model was constructed based on the human eye
      dimensions. To simulate intravitreal injection, unlike previous studies which
      considered the initial shape of the injected drug solution as a sphere or
      cylinder, the more accurate shape was obtained by level-set method in COMSOL. The
      results showed that in intravitreal injection the drug concentration profile and
      its maximum value depended on the injection time, needle gauge and penetration
      angle of the needle. Considering the actual shape of the injected solution was
      found necessary to obtain the real concentration profile. In implant insertion,
      the vitreous cavity received more drugs after intraocular implantation, but this
      method was more invasive compared to the periocular delivery. Locating the
      implant in posterior or anterior regions had a significant effect on local drug
      concentrations. Also, the shape of implant influenced on concentration profile
      inside the eye. The presented model is useful for optimizing the administration
      variables to ensure optimum therapeutic benefits. Predicting and quantifying
      different factors help to reduce the possibility of tissue toxicity and to
      improve the treatment efficiency. 

PMID- 24946305
TI  - Successful Endobronchial stenting for bronchial compression from a massive
      thoracic aortic aneurysm.
AB  - A case of bronchial occlusion caused by a thoracic aortic aneurysm and the relief
      of this obstruction by the implantation of expandable metallic stents is
      described. Stent deployment provided an immediate improvement in lung ventilation
      and chest radiograph appearances. Stent insertion was uncomplicated, but weaning
      from mechanical ventilation was unsuccessful and the patient died from a
      ventilator-associated pneumonia, unrelated to the procedure. Endobronchial
      stenting should be considered as a non-invasive therapy for the treatment of
      bronchial obstruction, with respiratory compromise, caused by a thoracic aortic
      aneurysm when vascular surgery is not an option. The medium to long term survival
      of this patient group is poor. This can be attributed to complications related to
      the stent and also to the poor performance status of these patients. 

PMID- 24946304
TI  - Post-surgical Pancreatitis Masquerading as Recurrent Neuroendocrine Cancer.
AB  - Neuroendocrine tumours of the pancreas can have a spectrum of behaviour from
      relatively benign to aggressive. Resection can result in cure although metastatic
      disease is described. We present an unusual case of an apparent local recurrence
      of previously resected neuroendocrine tumour in a young man who had undergone
      distal pancreatectomy. Pathological analysis demonstrated focal post-surgical
      pancreatitis with radiological appearances bearing striking similarity to the
      original primary tumour. 

PMID- 24946306
TI  - A rare case of mistaken identity: metastatic hepatocellular carcinoma to the
      nose.
AB  - Hepatocellular carcinoma most often metastasizes to the lungs, abdominal lymph
      nodes, or bone. The identification of extrahepatic metastases of hepatocellular
      carcinoma to the sinonasal region has rarely been reported. We report a case of a
      49 year-old man with a history of stage IV hepatocellular carcinoma presenting
      with two adjacent pigmented lesions on the tip of his nose. Initial pathological
      staining identified the lesion as a primary melanoma. However, upon further
      examination with the chemical markers CEA, CAM 5.2, and Keratin, it was
      determined that the lesions were consistent with hepatocellular carcinoma. This
      case highlights a potentially rare situation of mistaking a liver metastasis for
      a malignant melanoma. 

PMID- 24946307
TI  - Schistosomiasis: a rare cause of acute appendicitis.
AB  - Schistosomiasis is a parasitic infection in humans, which is prevalent in
      developing countries. The infection manifests itself as a variety of different
      pathologies, depending on the location of the parasite and its eggs. A rare
      manifestation is that of a common surgical presentation, acute appendicitis. We
      present a case of a young male who underwent appendicectomy for acute
      appendicitis caused by a schistosomiasis infection, proven on pathological
      examination of the resected appendix. 

PMID- 24946308
TI  - Osteo-myocutanoeus flap: a novel flap for single toe amputation.
AB  - Amputation is frequently required to treat wet gangrene secondary to peripheral
      vascular disease. Although different types of amputations have been reported,
      limited digital and ray amputation are the commonest amputations performed. The
      level of amputation will be determined by the distribution of lower limb disease
      but for every patient a balance between limb and functional preservation at lower
      levels versus better wound healing at higher levels should be sought. In this
      article we describe the novel osteo-myocutaneous flap, which we have used in our
      patient. We believe that this flap results in improved wound healing and although
      it results in loss of two digits, it does not impair function. 

PMID- 24946309
TI  - Radical exenteration surgery is curative in locally advance mucinous prostatic
      adenocarcinoma involving bladder and rectum.
AB  - The management of mucinous prostatic adenocarcinoma include hormonal treatment,
      radiotherapy and radical prostatectomy with variable long-term outcome. We report
      a 59 year old man with advanced mucinous prostatic adenocarcinoma involving
      almost the entire bladder and had failed treatment with hormonal and
      radiotherapy, but subsequently underwent radical pelvic exenteration surgery that
      resulted in long-term cure. He remains alive, his PSA remains undetectable and
      his surveillance CT scans did not show any evidence of recurrence after 11 years
      post-surgery. The favourable outcome of radical surgery suggests that radical
      surgery should be considered, especially in cases with failed initial treatments.

PMID- 24946310
TI  - Congenital bladder diverticulum with benign bladder wall lesion resembling
      rhabdomyosarcoma.
AB  - Congenital bladder diverticula in children are uncommon and rarely present with
      bladder outlet obstruction. We present a case highlighting an interesting
      association between a congenital bladder diverticulum and a benign inflammatory
      bladder wall lesion mimicking a rhabdomyosarcoma. Open surgery was required as
      different imaging modalities and cystoscopy were insufficient to exclude a
      malignant process. 

PMID- 24946311
TI  - Outcome of medical and surgical therapy of GERD: predictive role of quality of
      life scores and instrumental evaluation.
AB  - INTRODUCTION: Aim of this study is to determine whether quality of life (QoL)
      assessment in association with instrumental evaluation can help to identify
      factors predictive of outcome both in surgically and medically treated GERD
      patients. METHODS: Between January 2005 and June 2010, 301 patients affected with
      GERD were included in the study. QoL was evaluated by means of GERD-HRQL and SF
      36 questionnaires administered before treatment, at 6 months, at 1 year follow-up
      and at the end of the study. The multivariate analysis was used to detect if
      variables such as sex, age, heartburn, acid regurgitation, dysphagia, presence of
      esophagitis, percentage of total time at pH < 4, symptom index score (SI), the SF
      36 and HRQL scores before treatment, at 6 months and 1 year could affect the QoL
      questionnaires scores at the end of the study. RESULTS: One hundred forty-seven
      patients were included in the surgical group and 154 in the medical group. No
      differences with regard to gender, age, mean SF-36 and HRQL scores before
      treatment were documented. At the end of the study, quality of life was
      significantly improved for SF-36 and HRQL scores, either for surgical or medical
      group. The multivariate analysis showed no factors individually affected the SF
      36 and the HRQL scores, but symptom index score (SI) and QoL questionnaires
      scores at 6 months and 1 year follow-up. CONCLUSIONS: The combined use of pHmetry
      with evaluation of SI and QoL questionnaires can predict the outcome of GERD
      patients managed either by medical or surgical therapy.

PMID- 24946312
TI  - Touchscreen performance and knowledge transfer in the red-footed tortoise
      (Chelonoidis carbonaria).
AB  - In recent years red-footed tortoises have been shown to be proficient in a number
      of spatial cognition tasks that involve movement of the animal through space
      (e.g., the radial maze). The present study investigated the ability of the
      tortoise to learn a spatial task in which the response required was simply to
      touch a stimulus presented in a given position on a touchscreen. We also
      investigated the relation between this task and performance in a different
      spatial task (an arena, in which whole-body movement was required). Four red
      footed tortoises learned to operate the touchscreen apparatus, and two learned
      the simple spatial discrimination. The side-preference trained with the
      touchscreen was maintained when behaviour was tested in a physical arena. When
      the contingencies in the arena were then reversed, the tortoises learned the
      reversal but in a subsequent test did not transfer it to the touchscreen. Rather
      they chose the side that had been rewarded originally on the touchscreen. The
      results show that red-footed tortoises are able to operate a touchscreen and can
      successfully solve a spatial two-choice task in this apparatus. There was some
      indication that the preference established with the touchscreen could transfer to
      an arena, but with subsequent training in the arena independent patterns of
      choice were established that could be evoked according to the test context. 

PMID- 24946313
TI  - Prenatal and perinatal factors in eating disorders: a descriptive review.
AB  - OBJECTIVE: The objective of this descriptive review is to summarize the current
      scientific evidence on various prenatal and perinatal exposures affecting later
      development of eating disorders among offspring. METHOD: Studies were searched
      from PubMed database with the following keywords: eating disorders and disordered
      eating and anorexia nervosa and bulimia nervosa and binge eating disorder and
      prenatal exposure delayed effects and maternal exposure and perinatology. A
      comprehensive manual search, including search from the reference list of included
      articles, was also performed. RESULTS: The attributable risk for prenatal and
      perinatal factors in anorexia nervosa (AN) is 3.6%. Numerous prenatal and
      perinatal factors have been associated with offspring AN, but only prematurity
      has been replicated in different samples. The risk of bulimia nervosa (BN) in
      offspring has attracted less study, and despite varying positive associations,
      there are no replicated findings. Higher prenatal testosterone may protect
      against the development of a range of disordered eating symptoms, although
      studies are not consistent. DISCUSSION: Evidence in support of an effect of
      prenatal and perinatal factors on eating disorders or disordered eating in
      offspring is conflicting. If present, the overall effect appears to be relatively
      small, and it is likely that the early risk factors operate in conjunction with
      other biological, genetic, and/or environmental risk factors to bring on eating
      pathology. Genetically sensitive designs, such as sibling and twin studies, are
      needed to disentangle the different types of risk factors and ensure that
      prenatal/perinatal effects are "causal" rather than indications of genetic risk.

PMID- 24946315
TI  - Mediofrontal event-related potentials in response to positive, negative and
      unsigned prediction errors.
AB  - Reinforcement learning models make use of reward prediction errors (RPEs), the
      difference between an expected and obtained reward. There is evidence that the
      brain computes RPEs, but an outstanding question is whether positive RPEs
      ("better than expected") and negative RPEs ("worse than expected") are
      represented in a single integrated system. An electrophysiological component,
      feedback related negativity, has been claimed to encode an RPE but its relative
      sensitivity to the utility of positive and negative RPEs remains unclear. This
      study explored the question by varying the utility of positive and negative RPEs
      in a design that controlled for other closely related properties of feedback and
      could distinguish utility from salience. It revealed a mediofrontal sensitivity
      to utility, for positive RPEs at 275-310ms and for negative RPEs at 310-390ms.
      These effects were preceded and succeeded by a response consistent with an
      unsigned prediction error, or "salience" coding. 

PMID- 24946316
TI  - Psychological characteristics in musician's dystonia: a new diagnostic
      classification.
AB  - Numerous studies suggest that dysfunctional basal ganglia-thalamo-cortical
      circuits are involved in both movement disorders and psychiatric impairments. The
      current exploratory investigation explored possible psychological differences,
      firstly between 24 healthy musicians (HM) and 24 musicians diagnosed with focal
      dystonia (FDM) (Study I), and secondly among 35 FDM patients only (Study II).
      Results revealed that FDM patients are six times more likely to exhibit elevated
      anxiety, perfectionistic and stress characteristics than HM. These psychological
      conditions might contribute as aggravating risk factors to the development of
      FDM. However, half of the FDM patients did not demonstrate any signs of anxiety,
      perfectionism or stress. The findings point to the clear existence of two
      different psychological profiles among FDM patients. We suggest that this
      psychological distinction might reflect two different mal-adaptive processes
      mediated via different circuits of the cortico-basal ganglia-thalamicloops. The
      new classification of FDM patients will contribute to the reinforcement of the
      diagnostic repertoire, necessary for the selection of more specific treatment
      methods.

PMID- 24946314
TI  - Neural effects of cognitive control load on auditory selective attention.
AB  - Whether and how working memory disrupts or alters auditory selective attention is
      unclear. We compared simultaneous event-related potentials (ERP) and functional
      magnetic resonance imaging (fMRI) responses associated with task-irrelevant
      sounds across high and low working memory load in a dichotic-listening paradigm.
      Participants performed n-back tasks (1-back, 2-back) in one ear (Attend ear)
      while ignoring task-irrelevant speech sounds in the other ear (Ignore ear). The
      effects of working memory load on selective attention were observed at 130-210ms,
      with higher load resulting in greater irrelevant syllable-related activation in
      localizer-defined regions in auditory cortex. The interaction between memory load
      and presence of irrelevant information revealed stronger activations primarily in
      frontal and parietal areas due to presence of irrelevant information in the
      higher memory load. Joint independent component analysis of ERP and fMRI data
      revealed that the ERP component in the N1 time-range is associated with activity
      in superior temporal gyrus and medial prefrontal cortex. These results
      demonstrate a dynamic relationship between working memory load and auditory
      selective attention, in agreement with the load model of attention and the idea
      of common neural resources for memory and attention.

PMID- 24946317
TI  - Is a novel conceptual unit more than the sum of its parts?: FMRI evidence from an
      associative recognition memory study.
AB  - Recollection, an effortful process relying on the integrity of a brain network
      including the hippocampus, is generally required to remember arbitrary
      associations whereas a simple familiarity signal arising in the perirhinal cortex
      is sufficient to recognize single items. However, the integration of separate
      items into a single configuration (unitization) leads to reduced involvement of
      recollection and greater reliance on familiarity. This seems to imply that
      unitized associations are processed similar to single items. Here, using
      functional magnetic resonance imaging, we investigated the effects of unitization
      as encoding strategy on retrieval processes in a between-group-design. A
      definition was provided that allows combining two unrelated words into a novel
      conceptual unit (e.g., milk taxi = a delivery service, which is directly
      dispatched from a farm). We compared this to an encoding strategy in which the
      words were studied as parts of a sentence. We included pairs in reversed order at
      test because reversing a unitized word pair is assumed to disrupt the unit while
      leaving item familiarity for the single constituents intact. This enabled us to
      compare recognition memory for novel units and single items. Sentence encoding
      led to a flexible recruitment of brain areas previously associated with
      recollection, irrespective of the order of the test pair. Unitization encoding
      reduced the involvement of the recollection network and specifically engaged
      regions within the parahippocampal cortex and the medial prefrontal cortex for
      novel units. In contrast, recognition of reversed pairs involved activation of BA
      45 in the left inferior frontal gyrus. This possibly suggests that familiarity
      for novel units and single items are associated with different brain networks.

PMID- 24946319
TI  - Transoral incision free fundoplication (TIF) - A new paradigm in the surgical
      treatment of GERD.
AB  - An estimated 10 billion dollars is spent treating gastro-oesophageal reflux
      disease (GERD) in the USA every year. The present article reports a case of the
      safe and successful use of transoral incisionless fundoplication (TIF) using the
      EsophyX90TM device in the surgical treatment of GERD. 

PMID- 24946320
TI  - Oroantral fistula from bisphosphonate induced osteonecrosis of the jaw.
AB  - Bisphosphonates like alendronic acid, disodium etidronate, and risedronate are
      effective for preventing postmenopausal and corticosteroid induced osteoporosis.
      They are also useful in the treatment of Paget's disease, hypercalcaemia of
      malignancy and in bony metastases. However osteonecrosis of the jaw has been
      reported following intravenous bisphosphonate use and rarely in those taking them
      orally. Increasingly, oroantral fistulae have been shown to occur as sequelae of
      bisphosphonate-induced osteonecrosis of the jaw and this case report highlights a
      patient that presented to our ENT department and required sinus surgery in
      collaboration with maxillofacial surgeons. This case report aims to raise
      awareness among ENT surgeons to these patients on bisphosphonates that could
      present to them with sinus disease from oroantral fistulae. There is an on-going
      audit in the maxillofacial community on this emerging trend. 

PMID- 24946321
TI  - Laparoscopic plication of the linea alba as a repair for diastasis recti - a mesh
      free approach.
AB  - Distasis recti is a common occurrence in multiparous women (1), caused by
      repeated stretching of the abdominal wall by the gravid uterus. A small
      proportion of patients have a persisting weakness which may be symptomatic and
      present to the surgeon. We would like to present a case which, thus far, has had
      a successful outcome from laparoscopic plication of the linea alba without mesh.
      The benefits of this approach are as for any laparoscopic versus open technique,
      most notably improved recovery time, reduced pain and wound infection.
      Furthermore, avoidance of a mesh negates the risks associated with insertion of a
      foreign body. 

PMID- 24946318
TI  - Influence of the COMT val(108/158)met polymorphism on continuous performance task
      indices.
AB  - The Continuous Performance Task (CPT) is a widely-used measure of sustained
      attention and impulsivity. Deficits in CPT performance have been found in several
      psychiatric disorders, such as Attention-Deficit/Hyperactivity Disorder (ADHD)
      and schizophrenia. Molecular genetic studies of CPT performance are currently
      limited and have generally revealed inconsistent findings. The current study
      tested the associations of the COMT val(108/158)met polymorphism with AX-CPT
      indices (i.e., omission and commission errors, d', and lnbeta), as well as the
      variability of these indices across blocks, in a sample of clinic-referred and
      non-referred children (N=380). We found significant associations between COMT and
      variability in the Signal Detection Theory (SDT) indices d' and lnbeta across
      blocks, as well as a statistical trend for association between COMT and
      commission errors. Higher externalizing psychopathology was associated with
      general impairment on AX-CPT performance, and for some indices (i.e., d'
      variability and lnbeta variability) the effect of COMT was stronger at higher
      levels of psychopathology. Our findings support the role of COMT in components of
      CPT performance and highlight the potential utility of using SDT indices,
      particularly in relation to variability in performance. Moreover, our results
      suggest that for some indices the effect of COMT is stronger at higher levels of
      externalizing psychopathology. Our study yields some preliminary insights
      regarding the neurobiology of CPT performance, which may elucidate the mechanisms
      by which specific genes confer risk for various cognitive deficits, as well as
      relevant disorders characterized by these deficits.

PMID- 24946322
TI  - Haemosuccus pancreaticus due to true splenic artery aneurysm: a rare cause of
      massive upper gastrointestinal bleeding.
AB  - "Haemosuccus pancreaticus" is an unusual cause of severe upper gastrointestinal
      bleeding and results from rupture of splenic artery aneurysm into the pancreatic
      duct. More commonly, it is a pseudoaneurysm of the splenic artery which develops
      as sequelae of pancreatitis. However, true aneurysm of the splenic artery without
      pancreatitis has rarely been incriminated as the etiologic factor of this
      condition. Owing to the paucity of cases and limited knowledge about the disease,
      diagnosis as well as treatment become challenging. Here we describe a 60-year-old
      male presenting with severe recurrent upper gastrointestinal bleeding and
      abdominal pain, which, after considerable delay, was diagnosed to be due to
      splenic artery aneurysm. Following an unsuccessful endovascular embolisation, the
      patient was cured by distal pancreatectomy and ligation of aneurysm. 

PMID- 24946323
TI  - Spontaneous cholecystocutaneous fistula: a rare presentation of gallstones.
AB  - Spontaneous cholecystocutaneous fistula, one of the rarest complications of acute
      cholecystitis, has been reported in fewer than 25 cases over the past 50 years.
      Not only is this case rare but interestingly the patient experienced no pain or
      symptoms consistent with gallbladder pathology leading up to her hospitalisation.
      Furthermore, laboratory studies, microbiology and computed tomography scanning
      did not establish a diagnosis until the fistula passed calculi. An 85-year-old
      lady with multiple co-morbidities presented to the Emergency Department with an
      erythematous soft and non-tender mass in her right flank. The mass had
      spontaneously ruptured and was discharging a serous-like material. Prior to
      further investigation a working diagnosis of an eroding/fungating caecal tumour
      was made. The lesion continued to discharge over a 3 month period which heralded
      the passage of 11 small, brown calculi thought to be gallstones. At this point
      spontaneous cholecystocutaneous fistula was diagnosed and was later confirmed by
      magnetic resonance imaging cholangiopancreatography. 

PMID- 24946324
TI  - Malignant peripheral nerve cell sheath tumour of the upper lip: a rare case.
AB  - We present the case of a malignant peripheral nerve sheath tumour (MPNST) that
      developed on the upper lip of an 86 year old woman. MPNSTs are highly aggressive
      sarcomas that very rarely occur in the face. We know of no other reported cases
      of a malignant peripheral nerve sheath tumour arising from the upper lip. 

PMID- 24946325
TI  - Epithelioid angiosarcoma: Use of angiographic embolisation and radiotherapy to
      control recurrent haemorrhage.
AB  - Epithelioid angiosarcoma is a rare, highly malignant tumour with a poor
      prognosis. We present the case of a 75 year old man who underwent an incision
      biopsy to diagnose the soft tissue tumour and suffered from surgically
      uncontrollable haemorrhage. The case report demonstrates the value of
      interventional radiology for acute bleeding and radiotherapy for more chronic
      tumour bleeding. 

PMID- 24946326
TI  - Silent But Giant: Giant ureteric calculus in a 7-year-old boy.
AB  - Giant ureteric calculi are extremely rare in children. We present a case of a
      child who was originally admitted for observation following non-accidental injury
      and had an episode of painless haematuria as an inpatient. Ultrasonography
      demonstrated left hydronephrosis and a 2cm echogenic area in the proximal ureter.
      A plain abdominal radiograph surprisingly revealed two left ureteric calculi, one
      7cm and the other 4cm in length. Stone extraction was achieved using an open left
      ureterolithotomy and pyelolithotomy. 

PMID- 24946327
TI  - Spontaneous Thrombosis of a Bicuspid Aortic valve due to Primary Antiphospholipid
      Syndrome.
AB  - We present the case of a 51-year-old man who was admitted as an emergency with
      spontaneous thrombosis of the aortic valve and ascending aorta. At operation he
      was found to have a congenitally bicuspid aortic valve and subsequent
      investigation revealed primary antiphospholipid syndrome. He underwent successful
      removal of the thrombus combined with mechanical replacement of the aortic valve.

PMID- 24946328
TI  - Hypertension and a Large pulsatile neck mass: A Case of Malignant Glomus Vagale
      Tumour.
AB  - This teaching case report represents an unusual example of a neck mass in a
      previously healthy individual. The presence of a new neck mass is a relatively
      common head and neck problem and requires a full work up including a complete
      history and physical examination. With respect to our patient, thorough history
      taking, physical examinations and specific investigations led to the diagnosis of
      a malignant and functionally active paraganglioma. Vagal paraganglioma themselves
      are rare tumours and account for only 5-25% of all paragangliomas in the head and
      neck region. The presence of a malignant, functionally active, catecholamine
      secreting paraganglioma is even rarer and accounts for only 1-3% of all reported
      glomus vagale tumours. This case report illustrates the need to carefully monitor
      all neck masses for changes in size, for any distortion to surrounding
      structures, and their given function. 

PMID- 24946329
TI  - Refractory chylothorax following a transhepatic gunshot wound to the abdomen
      requiring unorthodox surgical treatment.
AB  - An 18 year-old-male sustained a gunshot wound to the abdomen which required an
      uneventful hepatorrhaphy. He later returned with a large right effusion and was
      diagnosed with a chylothorax. The output was persistent despite conservative
      measures. Thoracotomy with attempted thoracic duct ligation was unsuccessful at
      decreasing the output. Re-exploration and ligation of the thoracic duct was
      required thru an abdominal approach. 

PMID- 24946330
TI  - A vesicocutaneous fistula secondary to bladder calculi in a patient with spina
      bifida.
AB  - We present a rare case of a vesicocutaneous fistula secondary to two large
      bladder calculi in a patient with spina bifida. A 62 year old lady presented with
      swelling of her right thigh and a calcified mass protruding through the
      subcutaneous tissues of her right groin. Urine was seen to be draining from
      around the area and plain radiographs and a computed topography (CT) scan
      confirmed the presence of two bladder calculi with a vesicocutaneous fistula.
      Vesicolithotomy was performed and the fistula tract left to close spontaneously.
      Worldwide this is only the fourth case of a bladder calculus causing a
      vesicocutaneous fistula. 

PMID- 24946331
TI  - Acute Chest Presentation following a Laparoscopic Nissen Fundoplication.
AB  - We describe a case of an acute paraoesophageal hernia in the early post-operative
      period following a laparoscopic Nissen fundoplication. Patient developed
      intraoperative tension pneumothorax requiring an immediate chest drain and
      subsequently needed respiratory support of a continuous positive airway pressure
      (CPAP) ventilation. A short discussion of this rare but deleterious complication
      and the difficulty of making a prompt diagnosis are included as delayed revision
      surgery can be technically challenging with a poor outcome. 

PMID- 24946332
TI  - Incarcerated Gastro-thorax: a rare and delayed presentation of diaphragmatic
      injury due to multiple stab wounds.
AB  - Diaphragmatic injuries due to thoraco-abdominal penetrating trauma may often go
      unnoticed at the initial admission, especially in patients who are asymptomatic,
      with stable hemodynamic and respiratory parameters. Such occult diaphragmatic
      perforations can result in latent morbidity and mortality due to delayed trans
      diaphragmatic herniation of the abdominal viscera leading to incarceration,
      strangulation and perforation. Here we report a case of an initially asymptomatic
      patient who had sustained multiple truncal stab injuries and presented two months
      later with a trans-thoracic incarceration of the stomach which was accurately
      diagnosed and successfully repaired at the time of surgery. This case report
      highlights the importance of exploring thoraco-abdominal penetrating injuries
      even in the absence initial clinical and radiological signs, so as to promptly
      identify occult and isolated diaphragmatic perforations and prevent delayed
      catastrophes. The clinical features, radiological findings, diagnostic
      difficulties and surgical options are discussed along with review of relevant
      literature. 

PMID- 24946333
TI  - Resolution of Pseudotumor Cerebri following surgery for morbid obesity.
AB  - The cause of pseudotumor cerebri (PTC) is poorly understood although there is
      strong evidence that obesity plays a role in its development. This report
      describes a patient with medically intractable PTC, who had continued symptoms
      despite undergoing a ventriculo-peritoneal (VP) shunt. Following significant
      weight loss, as a result of laparoscopic gastric banding, she has been symptom
      free and off all medications for 11 months allowing VP shunt removal. Bariatric
      surgery should be strongly considered in morbidly obese patients with PTC. 

PMID- 24946334
TI  - Persistent medical management of chylopericardium following orthotopic heart
      transplant.
AB  - We describe a case of chylopericardium post orthotopic heart transplant, having
      had previous cardiac surgeries. This was managed conservatively for a prolonged
      period after which the patient recovered. We emphasise the fact that medical
      management works although the recovery time may be prolonged. 

PMID- 24946335
TI  - Anaphylaxis from intravascular rupture of Hydatid disease following liver trauma.
AB  - Cystic Echinococcosis also known as cystic hydatid disease is a parasitic
      infection endemic in many parts of the world. Humans are accidental intermediate
      hosts with cysts most commonly developing in the liver. This case describes a
      rare presentation of hydatid disease following trauma to the liver.
      Intraparenchymal cyst rupture led to haemodynamic instability with release of the
      parasites protoscolices into hepatic venules producing severe life threatening
      anaphylaxis. 

PMID- 24946336
TI  - Necrotizing Fasciitis Caused by Inconspicuous Infection of Aeromonas hydrophila
      in an Immunocompromised Host.
AB  - We present a case of serious necrotizing fasciitis due to Aeromonas hydrophila
      without a suggestive history of routes of pathogen invasion in a 60-year-old
      male. Despite prompt broad-spectrum antibiotic and extensive surgical therapies,
      the patient died within 72 hours following initial presentation. Our experience
      suggests clinicians be highly alert to the disease when an immunocompromised
      patient featured fulminant soft-tissue infection in the endemic area. 

PMID- 24946338
TI  - A novel method for intra-operative colonic decompression without contamination.
AB  - The need for intra-operative colonic decompression is commonplace within general
      surgical theatre. However, cases are usually complex, present late and the risk
      of perforation with subsequent contamination is high. We describe a novel
      technique for closed decompression using a laparoscopic trocar and standard pool
      sucker in a 78-year-old gentleman with an obstructing sigmoid tumour. 

PMID- 24946337
TI  - Transorbital Penetrating Intracranial Injury Caused by Sheppard's Hook.
AB  - Intracranial injury resulting from transorbital penetrating objects is rare in a
      noncombat setting. As such there is a significant lack of data pertaining to the
      management of non-projectile traumatic brain injuries due to foreign bodies
      entering the brain. Intracranial complications can include intracerebral
      hematoma, cerebral contusion, intraventricular hemorrhage, pneumocephalus, brain
      stem injury, and carotid cavernous sinus fistula. This is the first report of a
      transorbital penetrating intracranial injury caused by a Sheppard's hook, which
      was managed utilizing a multi-disciplinary, non-operative approach. 

PMID- 24946339
TI  - The use of intraoperative cholangiogram during laparoscopic double
      cholecystectomy.
AB  - Double gallbladder is a rare finding in patients with symptomatic cholelithiasis
      or acute cholecystitis. The incidence has been described as 1 in every 4000-5000
      patients during autopsy. To identify the gallbladder (GB) duplication prior to
      surgical removal of the GB is of upmost importance. It is not unusual to identify
      this diagnosis intraoperatively, but by using US, ERCP or MRCP more than 50% of
      the cases are diagnosed preoperatively. The use of intraoperative cholangiogram
      helps to identify the anatomy and confirm the diagnosis during laparoscopic
      cholecystectomy in patients with gallbladder duplication. 

PMID- 24946340
TI  - A rare case of Amyand's hernia presenting as an enterocutaneous fistula.
AB  - The finding of the vermiform appendix in an inguinal hernia has an incidence of
      approximately 1%. The condition is given the eponymous name Amyand's hernia.
      However in just 0.08% the condition is complicated by an acute appendicitis. The
      clinical presentation varies, depending on the extent of inflammation of the
      appendix and is most often misdiagnosed as an incarcerated inguinal hernia. As
      such it is rarely recognised prior to surgical exploration. We report a case of
      Amyand's hernia in an 85 year old woman, which presented as a right groin
      enterocutaneous fistula. CT scanning illustrated a fistulous tract in the right
      groin, which communicated with the caecum and the peritoneal cavity. She
      underwent laparotomy, which revealed that the appendix appeared inflamed, lay in
      the inguinal canal and was the origin of the enterocutaneous communication. 

PMID- 24946341
TI  - Carcinosarcoma of the oesophagus - a rare mixed type of tumor.
AB  - Oesophageal carcinosarcoma is a rare type of oesophageal cancer composed of both
      squamous cells and sarcomatous cells. We report a case of a 71 year old man
      presenting with dysphagia and weight loss. Oesophagogastroduodenoscopy revealed a
      bulky mass with a preliminary diagnosis of only oesophageal carcinoma, and the
      oesophageal mass was resected with a transhiatal oesophagectomy. On surgical
      pathology, it was discovered that the tumor had both squamous cell and
      sarcomatous cell components, and the final diagnosis was changed to oesophageal
      carcinosarcoma. We discuss the presentation, differential diagnosis, treatment,
      and prognosis of this unique entity. 

PMID- 24946342
TI  - Caecal bascule: a rare complication following emergency caesarean section.
AB  - Caecal bascule is an unusual type of volvulus that presents a challenging
      diagnosis for clinicians. We present a case of a forty-two year old female who
      developed a perforated caecal bascule five days post emergency caesarean section.
      The diagnosis of caecal bascule was made intraoperatively during a hemicolectomy.
      Greater awareness of this phenomenon and its clinical and radiological findings
      is important to avert the development of bowel perforation or gangrene. 

PMID- 24946343
TI  - Distal subgaleal-peritoneal shunt migration into the abdominal wall with
      subsequent formation of a pre-peritoneal pseudocyst: a rare complication.
AB  - Distal ventriculo-peritoneal shunt migration and extra-peritoneal CSF pseudocyst
      formation are unusual complications of shunt placement. We present a 65-year-old
      female who received a subgaleal-peritoneal shunt to decompress a post-surgical
      subgaleal fluid collection. Eight weeks later, shunt series showed tight coiling
      of the distal catheter, and operative exploration found the distal shunt tip to
      have migrated superficial to the rectus sheath, where it had become encapsulated
      in a pre-peritoneal CSF pseudocyst. Migration of the distal catheter into the
      abdominal wall was likely due to local inflammation of the inner surface of the
      abdomen, with pressure from intestinal peristaltic movements and intra-abdominal
      pressure, and continued inflammation at the distal catheter tip may have caused
      formation of a pre-peritoneal CSF pseudocystic dilatation. To date, this is the
      first reported case of distal shunt migration into the abdominal wall with
      subsequent formation of an extra-peritoneal pseudocyst and represents a rare
      event in the surgical management of peritoneal shunts. 

PMID- 24946344
TI  - Successful resection of a large incidentally found primary mediastinal
      liposarcoma.
AB  - Primary liposarcoma of the mediastinum is an uncommon tumour. We report a case of
      a 45-year-old female who was found incidentally to have a large anterior
      mediastinal mass. Complete removal of the tumour was accomplished successfully.
      Appropriate immunohistochimical stains were performed, confirming the presence of
      a well-differentiated liposarcoma of the mediastinum. We describe an unusual case
      of a large asymptomatic primary liposarcoma of the mediastinum. 

PMID- 24946345
TI  - Perinephric Capsular Haematoma Associated with Complicated Pyelonephritis in a
      Patient with HIV.
AB  - A 53 year-old-male patient presented with 24 hours of left flank pain. He was an
      undiagnosed HIV positive individual with no history of trauma. He was anaemic and
      in acute renal failure with a serum creatinine of 4.14 mg/dL. A CT scan
      demonstrated a left perinephric capsular haematoma with retroperitoneal
      stranding. Due to haemodynamic instability, the patient was taken to the
      operating room and a nephrectomy was performed. Post-operatively, the patient
      required temporary haemodialysis. Pathologic examination of the specimen
      demonstrated active infection with a haematoma surrounding a fistulous tract
      communicating with the capsular surface. Infection is a rare cause of non
      traumatic capsular hematomas of the kidney. 

PMID- 24946346
TI  - A Rare case of Intestinal Malrotation presenting as Appendicitis in Late
      Adulthood.
AB  - Appendicitis is a common surgical condition with various clinical presentations.
      The diagnosis could be obscured by underlying undiagnosed anatomical anomalies
      like intestinal malrotation. Intestinal malrotation is a rare foetal anomaly
      resulting from an incomplete, or failure of midgut rotation and fixation. 85% of
      cases have been estimated to present in the first two weeks of life. Presentation
      at adulthood is rare. In cases where peritonism is elicited elsewhere other than
      the right iliac fossa, clinicians should bear in mind the possibility of
      underlying intestinal malrotation, as this could be the first presentation of
      this rare congenital condition. 

PMID- 24946347
TI  - Management of ampullary carcinoid tumors with pancreaticoduodenectomy.
AB  - A 66 year old female was found to have an ampullary mass on endoscopic
      examination. A pancreaticoduodenectomy was performed and the pathology was
      consistent with carcinoid tumor. Carcinoid tumors of the ampulla of Vater are
      rare tumors of the gastrointestinal tract, accounting for 0.3-1% of
      gastrointestinal carcinoids. Management of ampullary carcinoid tumor with
      pancreaticoduodenectomy is in accordance with current recommendations. 

PMID- 24946348
TI  - Liver abscess or neoplasm? A diagnostic and surgical dilemma.
AB  - Hepatocellular carcinoma can is often associated with hepatitis B infection. With
      localised tumours, liver resection can result in a cure. This case presents an
      unusual finding of concurrent hepatitis B and liver fluke infection with
      hepatocellular carcinoma in a 50 year old man from Thailand. The discussion
      illustrates difficulties of arriving at a diagnosis and ensuring appropriate
      surgical management. 

PMID- 24946349
TI  - Hearing loss as an unusual consequence of metastatic gastric adenocarcinoma.
AB  - A sixty-one year old man was referred with a history of progressive dysphagia,
      vomiting and weight loss with some back pain. Upper gastrointestinal endoscopy
      and biopsies revealed a gastro-oesophageal junction adenocarcinoma. Despite the
      absence of metastatic disease on computed tomography, positron emission
      tomography demonstrated multiple vertebral and sternal deposits. He was reviewed
      in an ENT clinic with a sudden onset of hearing loss accompanied by dizziness,
      but no focal neurology. Magnetic resonance imaging identified bilateral 2cm
      lesions at the internal auditory meatus, consistent with a diagnosis of bilateral
      acoustic neuromas. The patient subsequently died of carcinomatosis and, because
      of the potential familial significance of bilateral acoustic neuromas, a limited
      post-mortem examination was carried out. Unexpectedly, this revealed bilateral
      adenocarcinoma metastases infiltrating the internal auditory meatus affecting the
      acoustic nerves. The authors believe this a very rare presentation of metastatic
      gastric disease. 

PMID- 24946350
TI  - Migratory abdominal pain.
AB  - A 63 year old woman, presenting as an emergency provides an useful example of the
      difficulties in diagnosing acute appendicitis when faced with an atypical
      history. This patient underwent plain radiography, computed tomography, repeat
      biochemical investigations and finally an exploratory laparotomy before the
      diagnosis of acute appendicitis was made. The case was confounded by a highly
      mobile caecal pole which brought the inflamed appendix to lie over the pancreas
      highlighting the need for vigilance in diagnosing acute appendicitis. 

PMID- 24946351
TI  - Use of TissuePatchDuralTM in the closure of an iatrogenic fistula following
      posterior semicircular canal occlusion surgery for intractable benign paroxysmal
      positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is a common disorder caused by the
      dislocation of otoconia most commonly into the posterior canal. The primary
      symptoms are brief episodes of head-position related vertigo which may be
      accompanied by nausea and disequilibrium. BPPV is usually managed conservatively
      with excellent results, however in a small number of cases the symptoms can
      become persistent and incapacitating. The most common treatment in such cases
      involves the surgical occlusion of the canal. This procedure carries a small risk
      of post operative perilymph leakage via an iatrogenic fistula. In this paper we
      outline a case of a patient who developed a perilymph leak following occlusion
      surgery for intractable BPPV. We describe a novel surgical method that was used
      to close the fistula using a synthetic polymer based patch
      (TissuePatchDural90TM), which has not been applied in the field of otology
      previously. 

PMID- 24946352
TI  - Management of a giant inguinoscrotal hernia with an ulcerated base in a patient
      with cardiac disease.
AB  - Giant inguinal herniae pose a surgical challenge, though not uncommon in the
      developing world they are a rare presentation in the UK. We present a patient
      with cardiac disease who presented with a giant inguino-scrotal hernia
      complicated by a bleeding scrotal ulcer. We describe his medical management and
      the surgical repair of the hernia and refashioning of his scrotum. 

PMID- 24946353
TI  - Appendicitis as a complication of colonoscopy.
AB  - Acute appendicitis is an extremely rare complication of colonoscopy, with no
      reports in the British literature. Here we discuss a case report of a patient who
      developed acute appendicitis 24 hours following a normal diagnostic colonoscopy.
      This case report highlights the rarity of this life threatening complication and
      discusses its aetiology. 

PMID- 24946355
TI  - Laparoscopic cholecystectomy in a patient with erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is an inherited defect in haem synthesis
      causing dangerous phototoxic reactions following exposure to wavelengths of light
      around 400nm. It can cause catastrophic post-operative complications following
      open surgery, in which environment various safety measures are now routinely
      employed. The dangers at laparoscopy have never been discussed in the literature,
      and nor have any specific precautions been recommended. We describe a 35 year old
      woman with gallstones undergoing prophylactic laparoscopic cholecystectomy to
      prevent future cholestasis precipitating porphyric liver failure. A pre-operative
      trial of the cutaneous effects of the laparoscopic light source was performed to
      assess the potential risk of use within the peritoneal cavity. The procedure was
      uneventful and the patient suffered no adverse reaction. We suggest that a trial
      of the effects of the laparoscopic light source on the skin of EPP patients
      provides valid reassurance regarding the safety of the laparoscopy for short
      surgical procedures. 

PMID- 24946354
TI  - An unusual perineal swelling: a cyst between the sphincters.
AB  - Epidermal cysts are very common lesions. Here we present the unusual case of an
      epidermal cyst occurring between the anal sphincters, presenting as a lump in the
      perineum. This was successfully excised with careful dissection of the
      intersphincteric plane. To our knowledge this is the only case of its kind
      reported in the literature. 

PMID- 24946356
TI  - Internal carotid artery ectasia: the value of imaging studies prior to biopsy of
      a retropharyngeal mass.
AB  - The presence of retropharyngeal tissue mass often raises the suspicion of
      malignancy, especially in elderly patients. This prompts urgent biopsy to
      investigate tissue histology. We discuss a case where this is contraindicated as
      the retropharyngeal mass was illustrated by CT scanning and confirmed with MRI to
      be a tortuous coursing internal carotid artery. An awareness of this unusual
      anatomical variation and a careful interpretation of imaging studies both at the
      stage of differential diagnosis and pre-operative screening are essential to
      avoid damage to important structures, causing unnecessary complications. 

PMID- 24946357
TI  - A rare gigantic solitary cysticercosis pseudotumour of the neck.
AB  - Cysticercosis is one of the ancient parasitic infections and endemic in many
      parts of the developing world. Humans acquire cysticercosis when they ingest pork
      tapeworm eggs either through faecal-oral route by eating faecally contaminated
      food or by auto infection. The clinical picture largely depends on the location
      of larval encystment. Neurocysticercosis is the most common form of presentation.
      Solitary extra neural lesions are quite rare and fairly small in size. We present
      a very unique case of 56 year old Malawian female with a very rare, long standing
      gigantic solitary cysticercosis pseudo tumour of the neck. By far, there is no
      documented report on incorrigible cysticercosis lesion with such a sheer size.
      Solitary extraneural cysticercosis lesions may mimic other soft tissue masses;
      therefore it is important for clinicians working in endemic regions to consider
      cysticercosis as a differential diagnosis when evaluating patients with soft
      tissue lesions. 

PMID- 24946358
TI  - Gallstone fistula with a gastric duplication cyst: an unusual complication of
      cholecystitis.
AB  - Cholecystitis can result in complications if not completely treated. These
      include gallbladder empyema, perforation and cholecystoenteric fistula. We report
      the first incidence of cholecystitis resulting in a gallstone fistula with a
      gastric duplication cyst. A 71 year old patient presented with generalised
      peritonism that was worst in the epigastric area. Computer tomography (CT)
      revealed a perforated necrotic gallbladder. Emergency laparotomy,
      cholecystectomy, partial gastrectomy and Roux-en-Y reconstruction was required.
      The patient made a slow but full recovery. Pathology results revealed that
      chronic cholecystitis had resulted in a fistula with a duplication cyst overlying
      the greater curve of the stomach. Several one centimeter gallstones were found
      within the cyst cavity. 

PMID- 24946359
TI  - Fibromatosis of the flexor pollicus longus tendon.
AB  - An unusual case of fibromatosis of the dominant left flexor pollicus longus (FPL)
      in a thirteen year old schoolboy. Initially presenting with pain in the thenar
      eminence and difficulty flexing the metacarpal phalangeal joint (MPJ), other
      symptoms include locking, triggering and difficulty writing. MRI showed a 4cm
      segment of thickened abnormal tendon. Intra-operatively three 1cm nodules were
      excised from the FPL while preserving the tendon. Histopathology reported the
      nodules as fibromatosis. A literature search revealed that this has not
      previously been reported although symptomatic tendon sheath fibromas have. Our
      patient achieved a good result following surgical intervention and the two year
      review has shown no complications. 

PMID- 24946360
TI  - Giant lactating adenoma of the breast.
AB  - Lactating adenoma is one of the breast tumours associated with pregnancy. A case
      of lactating adenoma, unusual on account of its huge size, is presented. Large
      size and history of rapid growth can lead to a mistaken diagnosis of malignancy.
      A review of the literature of this particular tumour with the different views on
      its histogenesis and the differential diagnoses are also discussed. 

PMID- 24946361
TI  - Ruptured internal iliac artery aneurysm presenting as Cullen's sign.
AB  - Cullen's sign or periumbilical ecchymosis, is classically considered as an
      indicator of acute hemorrhagic pancreatitis or ruptured ectopic pregnancy.
      Internal iliac artery aneurysms are rare and are usually asymptomatic. We present
      a case of a contained rupture of the internal iliac artery aneurysm presenting
      with Cullen's sign. 

PMID- 24946362
TI  - Transdiaphragmatic adrenalectomy for metastatic cervical adenocarcinoma: a
      technical case report.
AB  - We present a 60-year old woman with recurrent cervical adenocarcinoma who
      presented with metastasis to both lungs and to her right adrenal gland. A
      thoracotomy was performed for resection of her pulmonary metastasis and then the
      right adrenal gland was excised through a trans-diaphragmatic approach. The
      adrenal gland resection was more complex due to involvement of the tumor with the
      inferior vena cava (IVC) which was repaired with a PTFE patch graft. This case
      demonstrates both an interesting approach to surgical resection of multiple
      metastases as well as a safe, although more challenging, alternative to partially
      resect and repair the IVC. 

PMID- 24946363
TI  - Foreword: The role of nutrition and food insecurity in HIV and tuberculosis
      infections and the implications for interventions in resource-limited settings.

PMID- 24946365
TI  - Role of nutrition in HIV infection: review of evidence for more effective
      programming in resource-limited settings.
AB  - BACKGROUND: HIV infection and malnutrition negatively reinforce each other.
      OBJECTIVE: For program guidance, to review evidence on the relationship of HIV
      infection and malnutrition in adults in resource-limited settings. RESULTS AND
      CONCLUSIONS: Adequate nutritional status supports immunity and physical
      performance. Weight loss, caused by low dietary intake (loss of appetite, mouth
      ulcers, food insecurity), malabsorption, and altered metabolism, is common in HIV
      infection. Regaining weight, particularly muscle mass, requires antiretroviral
      therapy (ART), treatment of opportunistic infections, consumption of a balanced
      diet, physical activity, mitigation of side effects, and perhaps appetite
      stimulants and growth hormone. Correcting nutritional status becomes more
      difficult as infection progresses. Studies document widespread micronutrient
      deficiencies among HIV-infected people. However, supplement composition, patient
      characteristics, and treatments vary widely across intervention studies.
      Therefore, the World Health Organization (WHO) recommends ensuring intake of 1
      Recommended Nutrient Intake (RNI) of each required micronutrient, which may
      require taking micronutrient supplements. Few studies have assessed the impact of
      food supplements. Because the mortality risk in patients receiving ART increases
      with lower body mass index (BMI), improving the BMI seems important. Whether this
      requires provision of food supplements depends on the patient's diet and food
      security. It appears that starting ART improves BMI and that ready-to-use
      fortified spreads and fortified-blended foods further increase BMI (the effect is
      somewhat less with fortified-blended foods). The studies are too small to assess
      effects on mortality. Once ART has been established and malnutrition treated, the
      nutritional quality of the diet remains important, also because of ART's long
      term metabolic effects (dyslipidemia, insulin resistance, obesity). Food
      insecurity should also be addressed if it prevents adequate energy intake and
      reduces treatment initiation and adherence (due to the opportunity costs of
      obtaining treatment and mitigating side effects).

PMID- 24946364
TI  - Food insecurity in the context of HIV/AIDS: a framework for a new era of
      programming.
AB  - BACKGROUND: Food insecurity can be both a consequence and a driver of HIV/AIDS.
      It is often difficult to disentangle these two roles of food insecurity, since
      the HIV epidemic has different drivers in different settings. The advent of
      antiretroviral treatment in resource-limited settings adds an additional layer of
      complexity. This paper seeks to organize current thinking by reviewing the
      existing literature on food insecurity and HIV/AIDS and describing the complex
      interactions between them. OBJECTIVE: Based on literature review, the paper
      proposes a framework to understand the linkages, distinguishing four types of
      interventions to address them. It is hoped that the model, albeit simplified as
      is any framework, will help to structure research, policy, and programming in the
      field of HIV/AIDS and food insecurity. Finally, the paper intends to widen the
      lens to regard food not just as a means to provide calories or an income transfer
      but also as a carrier of adequate nutrition in the context of HIV. RESULTS AND
      CONCLUSIONS: An adequate response to HIV/AIDS and food insecurity must be
      tailored to specific settings. Interventions distinguished in this paper are
      aimed at both promoting food security and providing antiretroviral treatment and
      nutrition support. The four types of interventions are containing HIV and
      preventing AIDS through comprehensive treatment regimes that include nutritional
      support; mitigating the effects of AIDS through support; providing HIV-sensitive,
      but not HIV-exclusive, safety nets at the individual, household, and community
      levels; and limiting the exposure to risk through HIV prevention activities.

PMID- 24946366
TI  - Addressing tuberculosis in the context of malnutrition and HIV coinfection.
AB  - BACKGROUND: Tuberculosis is the second leading cause of infectious disease
      mortality (1.8 million/year), after HIV/AIDS. There are more than 9 million new
      cases each year. One-third of the world's population, and 50% of adults in sub
      Saharan Africa, South Asia, and South-East Asia, are infected, representing an
      enormous pool of individuals at risk for developing the disease. The situation is
      complicated by the HIV/AIDS pandemic, widespread undernutrition, smoking,
      diabetes, increased mobility, and emergence of multi- and extensively drug
      resistant tuberculosis. OBJECTIVE: To review the scientific evidence about the
      interactions among tuberculosis, nutrition, and HIV coinfection. RESULTS: HIV
      infection and malnutrition lower immunity, increasing the risk of reactivation
      tuberculosis and primary progressive disease. Having either tuberculosis or HIV
      infection causes weight loss. Malnutrition markedly increases mortality among
      both tuberculosis and HIV/AIDS patients and should be treated concurrently with
      treatment of the infections. Tuberculosis treatment is a prerequisite for
      nutritional recovery, in addition to intake of nutrients required for rebuilding
      tissues, which is constrained in food-insecure households. Additional
      pharmaceutical treatment to reduce the catabolic impact of inflammation or
      promote growth may be needed. Specific nutrients can contribute to faster sputum
      smear clearance, which is important for reducing transmission, as well as faster
      weight gain when combined with an adequate diet. Adequate nutrition and weight
      gain in undernourished populations might reduce the incidence of tuberculosis.
      CONCLUSIONS; The many risk factors for the development of tuberculosis need to be
      addressed simultaneously, especially HIV/AIDS and food insecurity and
      undernutrition. For stronger evidence-based guidelines, existing recommendations
      and clinical applications need to be more widely applied and evaluated.

PMID- 24946367
TI  - Iron deficiency anemia in late preterm infants.

PMID- 24946368
TI  - Neural networks and learning systems come together.

PMID- 24946369
TI  - Opioid overuse pain syndrome.

PMID- 24946370
TI  - Authors' response.

PMID- 24946371
TI  - Government. Shinseki exit won't fix VA woes.

PMID- 24946372
TI  - Government. Hospitals brace for challenges serving more vets.

PMID- 24946373
TI  - Regulation. Bill due for drugmakers' winning strategy.

PMID- 24946374
TI  - Rating the raters. Experts raise questions about hospital raters' assorted
      methods and lack of transparency.

PMID- 24946375
TI  - Patient-friendlier financing? Hospitals and vendors tout new no-interest payment
      plans.

PMID- 24946376
TI  - Ensuring competition begins with transparency.

PMID- 24946377
TI  - Safety net hospitals can thrive under reform.

PMID- 24946378
TI  - Blending Catholic, Jewish and academic cultures into a 'rich stew'.

PMID- 24946380
TI  - Look ahead to succeed under VBP.
AB  - The Centers for Medicare & Medicaid Services (CMS) is adding new metrics to its
      Value-based Purchasing Program each year, and case managers should look ahead to
      ensure that their hospital performs well on the measures. CMS automatically
      withholds a percentage of the Medicare base operating payment each year (1.5% in
      fiscal 2015), and hospitals can earn back what was deducted or more by performing
      well. Value-based purchasing for 2015 includes four domains: clinical processes
      of care, outcomes, Hospital Consumer Assessment of Healthcare Programs and
      Systems (HCAHPS), and hospital efficiency of care. Any measure that is in the
      Inpatient Quality Reporting Program is considered to be on deck for value-based
      purchasing.

PMID- 24946379
TI  - Discharge planning takes spotlight as VBP focuses on efficiency.
AB  - Hospital efficiency of care, a new domain in the Centers for Medicare & Medicaid
      Services Value-based Purchasing Program, bases hospital scores on spending three
      days before admission through 30 days after discharge. Case managers need to take
      the time to develop a discharge plan that works and look at cost-effectiveness as
      well as appropriateness of the level of care, experts say. Because the data used
      for this measure is risk-adjusted, it's crucial for the documentation in the
      medical record to clearly and accurately reflect the patient's severity of
      illness. Become familiar with all the potential discharge destinations and spend
      time with each provider, experts recommend.

PMID- 24946381
TI  - Documentation must be complete and accurate.
AB  - If discharge documentation isn't complete and accurate, coders may not use the
      correct discharge status code, which could affect a hospital's reimbursement.
      Discharge status codes identify where patients go after discharge. If patients go
      to some settings before the geometric mean length of stay, a hospital may receive
      reduced reimbursement. The Centers for Medicare & Medicaid Services has also
      issued a new set of discharge status codes that indicate scheduled readmissions.

PMID- 24946382
TI  - CMS emphasizes quality patient care.
AB  - The Inpatient Prospective Payment System proposed rule for fiscal 2015 continues
      the Centers for Medicare & Medicaid Services' move toward basing reimbursement on
      quality of care, not quantity. The rule also asks for public input on the two
      midnight rule and a policy to address short-stay patients. CMS is implementing
      the Hospital-Acquired Condition Reduction Program, which penalizes hospitals that
      perform poorly. The agency proposes to add two safety measures to value-based
      purchasing in the future.

PMID- 24946383
TI  - Redesign promotes patient-centered care.

PMID- 24946384
TI  - Transitional care nurses help prevent readmits.

PMID- 24946385
TI  - Statewide effort cuts readmissions.

PMID- 24946386
TI  - A cross-cultural investigation into the relationships among parental support for
      basic psychological needs, sense of uniqueness, and happiness.
AB  - A significant number of empirical studies have reported that parental support for
      basic psychological needs is a robust correlate of adolescent happiness. Yet,
      less is known about the mechanisms responsible for this link. The present study
      proposed a model suggesting that personal sense of uniqueness explains why
      satisfaction of basic psychological needs in parent-child relationships is
      related to happiness. This mediational model was tested among late adolescents in
      Turkey and the United States. Analyses relying on structural equation modeling
      and bootstrapping supported the model in both cultures. Implications of the
      findings for theory and cross-cultural research are discussed. Directions for
      future research that could improve our understanding of the dynamic interplay
      between basic needs, sense of uniqueness and well-being are provided.

PMID- 24946387
TI  - Perceptions about parents' relationship and parenting quality, attachment styles,
      and young adults' intimate expectations: a cluster analytic approach.
AB  - This study examines the associations between young adults' perceptions of their
      parents' intimate relationship and the quality of their parenting as predictors
      of their children's expectations about intimacy in their own future
      relationships. A sample of 111 young adults completed questionnaires assessing
      their perceptions regarding their parents' intimate relationship and parenting
      quality, their own attachment styles, and their own expectations regarding
      intimate relationships. A correlational analysis revealed a positive link between
      the parents' relationship and parenting quality, and between parenting quality
      and expectations about intimacy, which supports the attachment theory. A cluster
      analysis identified three distinct groups of parental profiles interrelated with
      attachment styles that had varying effects on their children's expectations about
      intimacy. These findings emphasize the unique characteristics of parental
      relations in the family of origin relations, which have an enduring effect on the
      interpersonal styles of adult children, providing additional support to an
      integrated, intergenerational approach to family dynamics.

PMID- 24946388
TI  - Flowing together: a longitudinal study of collective efficacy and collective flow
      among workgroups.
AB  - The aim of this study is to extend the Channel Model of Flow (Csikszentmihalyi,
      1975, 1990) at the collective level (workgroups) by including collective efficacy
      beliefs as a predictor of collective flow based on the Social Cognitive Theory
      (Bandura, 1997, 2001). A two-wave longitudinal lab study was conducted with 250
      participants working in 52 small groups. Longitudinal results from Structural
      Equation Modeling with data aggregated at the group level showed, as expected,
      that collective efficacy beliefs predict collective flow over time, both being
      related reciprocally. Findings and their theoretical and practical implications
      in the light of Social Cognitive Theory are discussed.

PMID- 24946389
TI  - The image of psychology programs: the value of the instrumental-symbolic
      framework.
AB  - As competition for funding and students intensifies, it becomes increasingly
      important for psychology programs to have an image that is attractive and makes
      them stand out from other programs. The current study uses the instrumental
      symbolic framework from the marketing domain to determine the image of different
      master's programs in psychology and examines how these image dimensions relate to
      student attraction and competitor differentiation. The samples consist of both
      potential students (N = 114) and current students (N = 68) of three psychology
      programs at a Belgian university: industrial and organizational psychology,
      clinical psychology, and experimental psychology. The results demonstrate that
      both instrumental attributes (e.g., interpersonal activities) and symbolic trait
      inferences (e.g., sincerity) are key components of the image of psychology
      programs and predict attractiveness as well as differentiation. In addition,
      symbolic image dimensions seem more important for current students of psychology
      programs than for potential students.

PMID- 24946390
TI  - A social values analysis of parental decision making.
AB  - Social values theory was used to examine how parents make decisions for their
      adolescent children. Social values theory states that decision making for others
      is based on the social value of an action, leading to a norm for how to decide
      for others, whereas self decisions are influenced by a number of additional
      factors. Consistent with a risk-aversion norm, in hypothetical health and safety
      scenarios parents made more risk and inconvenience affected self decisions more
      risk-averse decisions for their adolescent children than for themselves. Further,
      the level of riske than decisions for one's child. A second study showed that the
      norm was stronger for decisions for one's child than for oneself and more related
      to parents' decisions for their child than for themselves. In sum, parents'
      decisions for their children seem to be largely determined by a norm stating how
      they are supposed to decide, at least in the domain of health and safety.
      Implications for both the judgment and decision making and parenting literatures
      are discussed.

PMID- 24946391
TI  - [Genetic polymorphisms commonly influencing efficacy of diverse addictive
      substances].
AB  - Opioids, such as morphine and fentanyl, are widely used as effective analgesics
      for the treatment of acute and chronic pain. In addition, the opioid system has a
      key role in the rewarding effects of morphine, ethanol, cocaine and various other
      drugs. The authors have focused on G-protein-activated inwardly rectifying
      potassium (GIRK) channel subunits, GIRK2 and GIRK3, that are important molecules
      in opioid transmission, and found that the single-nucleotide polymorphisms (SNPs)
      within the GIRK2 and GIRK3 gene regions were significantly associated with
      postoperative requirements of analgesics including opioids in patients who
      underwent abdominal surgery and mRNA expression of these genes in postmortem
      specimens, one of which was also associated with vulnerability to methamphetamine
      (METH) dependence. Further, by conducting a multistage genome-wide association
      study (GWAS) in healthy subjects, the authors found that genetic polymorphisms
      within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly
      associated with the requirements for postoperative opioid analgesics after
      painful cosmetic surgery. The C allele of the best candidate SNP, rs2952768, was
      associated with more analgesic requirements, and consistent results were obtained
      in patients who underwent abdominal surgery. In addition, carriers of the C
      allele in this SNP exhibited less vulnerability to severe drug dependence in
      patients with methamphetamine dependence, alcohol dependence, and eating
      disorders and a lower 'Reward Dependence score on a personality questionnaire in
      healthy subjects. Furthermore, the C/C genotype of this SNP was significantly
      associated with the elevated expression of a neighboring gene, CREB1. The results
      show that SNPs in this locus are the most potent genetic factors associated with
      human opioid sensitivity known to date, affecting both the efficacy of opioid
      analgesics and liability to severe substance dependence. These outcomes provide
      valuable information for the personalized treatment of pain and drug dependence.

PMID- 24946392
TI  - [Involvement and plasticity of brainstem cholinergic neurons in cocaine-induced
      addiction].
AB  - Although the involvement and plasticity of the mesocorticolimbic dopamine (DA)
      system in cocaine-induced addiction have been studied extensively, the role of
      the brainstem cholinergic system in cocaine addiction remains largely unexplored.
      The laterodorsal tegmental nucleus (LDT) contains cholinergic neurons that
      innervate the ventral tegmental area (VTA) and is crucial for regulating the
      activity of VTA DA neurons, implying that LDT may also be associated with cocaine
      addiction. In this review, we summarize our recent findings showing that
      cholinergic transmission from the LDT to the VTA is involved in acquisition and
      expression of cocaine-induced conditioned place preference and that, after
      repeated cocaine exposures, these neurons exhibit synaptic plasticity, which is
      dependent on NMDA receptor activation, nitric oxide production, and the activity
      of medial prefrontal cortex. The findings strongly suggest that LDT cholinergic
      neurons may critically contribute to developing cocaine-induced addiction.

PMID- 24946393
TI  - [Study on job support programs for drug addicts in japan: results of a nationwide
      survey on drug addiction rehabilitation centers (DARC)].
AB  - In Japan, many drug addiction rehabilitation centers (DARC) provide various types
      of recovery programs for drug addiction. The purpose of this study was to clarify
      the attitudes of DARC staff and users regarding job support programs. A
      nationwide questionnaire survey was conducted in 2009. The staff of 46 facilities
      and 606 users returned questionnaires. The results indicated that many (92.1%)
      users had work experience before entering the recovery programs provided by DARC
      and about half (49.3%) of the users reported being motivated to work. Although
      many DARC have established various job support programs, the users faced various
      levels of anxieties to get employed and 60.4% of the users expected to learn more
      detailed and concrete methods for finding a job. Through the DARC programs, the
      users gradually realize the significance of basic daily living skills such as
      maintaining their rhythm of life or neat and presentable appearance. And the more
      they get recovered the more they understand the significance of "self-care" and
      "interpersonal relationship skills". These findings indicate that job support
      programs for drug addicts should also focus on these recovery processes. More
      extensive job supports dealing with more practical issues and covering a wide
      variety of anxieties would be imperative.

PMID- 24946394
TI  - [Evaluation of the relapse prevention program for substance abusers called
      "TAMARPP" at mental health and welfare center].
AB  - We developed the TAMA mental health and welfare center Relapse Prevention Program
      (TAMARPP) and evaluated the efficacy of the program. We provided the program for
      59 substance abusers at Tokyo Tama Comprehensive Mental Health and Welfare
      Center, and conducted brief interviews and questionnaire surveys to them four
      times during eight months follow-up period. The main results were as follows. 1)
      Most of the subjects were before "hitting bottom". 2) More than half of the
      subjects continued participating in the program for more than 2 months and their
      attendance rate was fairly high. 3) Some of the subjects began joining a self
      help group as N.A. and A.A. during the follow up period. 4) The mood states of
      the subjects were gradually improved during the period. 5) About one-third of the
      subjects abused substance again after two-month' program, but all of them
      continued to attend the program or a private counseling. Most of their families
      also continued having support from the center. These findings suggested it was
      meaningful to have such a friendly and less confrontational program as TAMARPP at
      our center to provide support for many substance abusers before "hitting bottom"
      and their families.

PMID- 24946395
TI  - [The outcome of patients with alcoholic liver cirrhosis].
AB  - We investigated the outcome of the patients with alcoholic liver cirrhosis who
      had visited our hospital from 2007 to 2013. We compared them with the patients
      with type C liver cirrhosis, matched in gender and in age. The patients with
      alcoholic liver cirrhosis who dropped out accounted for 19.3% (17 cases) of the
      whole. In 401 days of mean treatment period, the median value of the dropout
      patients was 43 days, indicating that a number of the patients dropped out in an
      early stage. The percentage of abstinence from alcoholic drinking was 35.3% in
      the dropout groups, whereas it was 67.6% in the non-dropout groups. It was
      conceivable that the abstinence was difficult for the dropout groups to perform.
      The percentage of the dropout in patients receiving livelihood protection was
      35.7%, which was higher than that in general patients. There were no differences
      of the rate of dropout in general patients between alcoholic and type C liver
      cirrhosis. Since none of the patients with type C liver cirrhosis receiving
      livelihood protection dropped out, it was speculated that the cause of liver
      cirrhosis may be related to the rate of dropout. In summary, a number of patients
      with alcoholic liver cirrhosis have a difficulty in abstinence from alcoholic
      drinking. We also have to be careful to the high rate of dropout in patients with
      alcoholic liver cirrhosis receiving livelihood protection. In addition, it was
      thought that early incentive and education were important for these patients.

PMID- 24946396
TI  - Future challenges for palliative care.

PMID- 24946397
TI  - Gaining stronger recognition for nursing professionalism.

PMID- 24946398
TI  - Midwives have issues heard.

PMID- 24946399
TI  - Study of UK-trained nurses.

PMID- 24946400
TI  - Volunteering in Thai orphanage.

PMID- 24946401
TI  - Supporting Vietnam orphanages.

PMID- 24946402
TI  - Evils of our day.

PMID- 24946403
TI  - Equal pay case is a Pandora's box--Bartlett.

PMID- 24946405
TI  - Letting the conversations begin.

PMID- 24946404
TI  - Sustainable solution needed for new graduate employment.

PMID- 24946406
TI  - What whanau need at the end of life.

PMID- 24946407
TI  - Whanau respond to tangihanga and grief.

PMID- 24946408
TI  - Wanted: investment in public health.

PMID- 24946409
TI  - Attending to end-of-life needs.

PMID- 24946410
TI  - Self-care vital for palliative nursing team.

PMID- 24946411
TI  - Nurse specialist focuses on whanau, not the illness.

PMID- 24946412
TI  - Promoting quality of life.

PMID- 24946413
TI  - Buying medicine online is risky business.

PMID- 24946414
TI  - Valuing nurses' stories.

PMID- 24946415
TI  - Professionally yours:.

PMID- 24946416
TI  - Nurturing hope and action.

PMID- 24946417
TI  - Capturing demand for care accurately.

PMID- 24946418
TI  - Respiratory nursing: managing breathlessness better.

PMID- 24946419
TI  - Mental health: debunking myths around suicide.

PMID- 24946420
TI  - Nurses' voice heard in Dunedin.

PMID- 24946421
TI  - Health spokespeople criticise targets.

PMID- 24946422
TI  - Who loses when a state declines the Medicaid expansion?

PMID- 24946423
TI  - Addressing mental health stigma among young adolescents: evaluation of a youth
      led approach.
AB  - Stigma around mental illness puts adolescents at risk for not seeking help for
      themselves or helping peers dealing with mental distress. This program evaluation
      looks at a youth-led mental health awareness promotion campaign, in which high
      school students led educational workshops for at-risk middle school students in
      an after-school program. Pre- and posttests were used to measure knowledge about
      mental illness as well as social distance; a total of 57 pre- and posttests were
      analyzed. Analyses revealed statistically significant changes in both the
      Knowledge and Social Distance scales. The results suggest that salutary results
      can be realized as a result of very brief intervention with youths around the
      topic of mental health awareness.

PMID- 24946424
TI  - Understanding the relationship between school-based health center use, school
      connection, and academic performance.
AB  - School-based health centers (SBHCs) benefit the overall health of underserved
      communities. In fact, there is an abundance of evidence suggesting the positive
      effects that SBHCs have on physical and mental health. However, research related
      to understanding the relationship of SBHCs to academic outcomes such as
      performance and school connectedness is sparse. The purpose of the current study
      was to (a) compare differences between elementary, middle, and high school
      student SBHC users and nonusers on school connectedness and (b) test the pathways
      between SBHC usage and academic performance. A structural equation model was
      tested and found significant pathways between SBHCs, school connectedness, and
      academic performance.

PMID- 24946425
TI  - Experiences with pregnancy of adolescents with disabilities from the perspectives
      of the school social workers who serve them.
AB  - Adolescents with disabilities are more likely than adolescents without
      disabilities to become pregnant, although very little is known about the lived
      contexts of their sexual and pregnancy experiences. Such youths are often
      deprived of sexual health information across a range of potential sources,
      although school social workers are in a unique position to provide them services.
      Thirteen school social workers working primarily with adolescents with
      disabilities were interviewed using a phenomenological study design to offer
      their perspectives concerning the sexual and pregnancy experiences of such
      youths. Inductive content analysis revealed that school social workers provided
      services for pregnant and parenting adolescents with a range of disabilities in
      areas that included making decisions about sex, deciphering whether they were
      pregnant, and making decisions once they were pregnant. These experiences were
      complicated by cognitive impairments; emotional struggles; desires to fit in with
      peers; histories of sexual abuse; and issues with communication, self-esteem, and
      impulsivity. School social workers play an integral role in preventing pregnancy
      and supporting adolescents with disabilities who are pregnant. Recommendations
      pertaining to the provision of sexual health services for adolescents with
      disabilities are provided.

PMID- 24946426
TI  - Everyone deserves a second chance: a decade of supports for teenage mothers.
AB  - Georgia had the third highest 2010 repeat teenage birth rate in the United States
      and has had one of the worst rates for years. Since 2001, Georgia's Second Chance
      Home Network, administered by the Georgia Campaign for Adolescent Power and
      Potential, has provided housing and support to parenting teenagers--almost two
      thirds of whom were in custody of and referred by Georgia's Department of
      Children and Family Services--to help them become nurturing and self-sufficient
      parents, to avoid repeat teenage pregnancies, and to promote healthy development
      of their children. Data were collected from each resident at intake, discharge,
      and three follow-up points at three, 12, and 24 months after discharge.
      Evaluation has consistently revealed improvements in several key outcomes,
      including education, housing, income, self-sufficiency, parenting, repeat
      pregnancy, and child outcomes. The 2012 evaluation revealed benefits in all these
      areas and found that those who stayed longer demonstrated better outcomes,
      especially related to the core outcomes of educational status, employment, and
      stable residence. Methods and findings about these outcomes are featured in this
      article.

PMID- 24946427
TI  - How bipartisanship and incrementalism stitched the child health insurance safety
      net (1982-1997).
AB  - Today, 96.5 percent of children and adolescents either have health insurance or
      are uninsured but eligible for a public plan. This proportion far exceeds the
      most optimistic coverage projections for adults under the Patient Protection and
      Affordable Care Act. The child health insurance safety net was crafted from 1982
      to 1997 through several incremental, bipartisan federal and state legislative
      actions. It began by offering and later mandating state Medicaid eligibility
      expansions and culminated with the enactment of the State Child Health Insurance
      Program. Two-thirds of the states leveraged these laws to expand coverage beyond
      federal requirements. As a senior executive with the American Academy of
      Pediatrics, the author was directly involved or closely monitored these federal
      and state child health insurance expansions. This case study is a participant
      observer analysis of that period, an era that stands in stark contrast to today's
      highly partisan times. The successive expansions of publicly funded children's
      health insurance during this conservative period, when many other human services
      programs were slashed, are attributed to public sympathy for children, political
      acceptability by the right and the left, manageable costs, and the relative ease
      of state implementation as these changes came in incremental pieces over several
      years.

PMID- 24946428
TI  - Social work should embrace doulas.

PMID- 24946430
TI  - Constrained access to child health care as a result of clinical workforce
      composition and geographic maldistribution.

PMID- 24946429
TI  - Disparities in insurance coverage among children with special health care needs:
      how social workers can promote social and economic justice.

PMID- 24946431
TI  - [Neurological soft signs as a candidate for endophenotype of schizophrenia].
AB  - A concept of an endophenotype, also termed as an internal endophenotype, is used
      in genetic studies on psychiatric disorders. Neurological soft signs are also
      considered candidates for endophenotypes of schizophrenia. Neurological soft
      signs are, objectively measured, non-localizing abnormalities, not related to
      impairment of a specific brain region, reflecting improper cortical-subcorical
      and intercortical connections. This paper presents the main domains of NSS,
      methods of measurement of NSS, their neuroanatomical substrate, association of
      NSS with schizophrenia symptoms the and analysis of the literature in order to
      check whether NSS meet the criteria of the phenotype. A marker can be considered
      a phenotype if it meets the following criteria: 1) association with a disease in
      a population, 2) heritability, 3) state-independence, 4) familial association
      (the endophenotype is more prevalent in the affected individuals, their affected
      and non-affected family members in comparison to the normal population), 5) co
      segregation (the endophenotype is more prevalent among ill family members of ill
      probands compared with healthy relatives). Currently, there is an ample evidence
      that the NSS, especially these representing impaired motor coordination, meet
      certain criteria of an endophenotype. However, there are still several unresolved
      questions concerning NSS: studies on relatives of schizophrenic patients included
      small groups of subjects, many of the studies included individuals with
      schizophrenia, as well as schizophrenia spectrum disorders, the available date
      base of twins (schizophrenia-concordant and schizophrenia non -concordant) is not
      sufficiently large, there are too few studies evaluating the relationship of NSS
      and individual genes, there are no objective and quantitative methods of
      measurement of NSS. Therefore, NSS still represent only candidates for an
      endophenotype of schizophrenia. Finding correlations of selected NSS with other
      endophenotypes and their genetic correlates also needs further investigation and
      may provide a definitive answer to the question of the usefulness of NSS as the
      endophenotype of schizophrenia.

PMID- 24946432
TI  - [Oxytocin model of formation of psychotic symptoms and its implications for
      research on oxytocinergic pathway in schizophrenia].
AB  - There are more and more data to support the dysregulation of the oxytocinergic
      pathway in schizophrenia. The development of the above branch of knowledge began
      to evolve alongside the mainstream of studies concerning gene polymorphisms for
      dopaminergic, glutamatergic and serotoninergic systems. Both experimental studies
      and clinical trials have demonstrated an antipsychotic effect of oxytocin.
      Starting with the pioneering neuroendocrinobehavioral experiment which
      demonstrated that oxytocin nasal spray increases the level of trust in healthy
      volunteers dozens of experiments were carried out confirming the modulatory role
      of oxytocin for the recognition of emotion, social memory, pro-social behaviours,
      collaborative behaviours and behaviours that require generosity and altruism.
      According to,oxytocin model' of development of psychotic symptoms--oxytocinergic
      system dysregulation may affect the incorrect attribution of meaning of emotional
      information from the environment. This can be manifested in the form of social
      cognition dysfunction and leads to abnormal social behaviour as withdrawal from
      social contact, isolation and formulation of paranoid delusions. From the
      clinical psychiatry point of view it became crucially need for research on
      selective oxytocin receptor agonists, as they may be used in the treatment of
      diseases which manifest in social withdrawal, lack of trust and the absence of
      affiliation behaviour as in schizophrenia.

PMID- 24946433
TI  - [Factors connected with efficacy of single ketamine infusion in bipolar
      depression].
AB  - AIM: The aim of this study was to evaluate the efficacy of single ketamine
      infusion and clinical and biochemical factors connected with such efficacy, in
      patients with bipolar depression, which had not improved on antidepressant
      treatment. METHODS: The study included 42 patients (32 women, 10 men), aged 22-67
      years, with bipolar depression. They received > or = 1 mood-stabilizing
      medications of first and/or second generation. After discontinuation of
      antidepressants (> or = 7 days), intravenous infusion of ketamine (0.5 mg/kg body
      weight) was performed. The assessment of depression by the 17-item Hamilton
      Depression Rating Scale was made before, and after 1, 3, 7 and 14 days following
      administration of ketamine. The assumed criterion for clinical improvement was
      the reduction of > or = 50% score on the Hamilton scale after 7 days. In a
      subgroup of 20 patients, prior to administration of ketamine, serum
      concentrations of homocysteine, vitamin B12, folic acid, neurotrophins and
      inflammatory proteins were measured. RESULTS: In the whole group, the severity of
      depression on the Hamilton scale decreased significantly 24 hours after
      administration of ketamine from 22.6 +/- 5.1 to 15.6 +/- 7.4 points. After 7 days
      it was 13 +/- 7 and after 14 days - 11.8 +/- 7.8 points. Patients showing
      clinical improvement (n = 22) had significantly higher frequency of alcohol
      addiction and family history of alcoholism. Biochemical tests in the subset of 20
      patients demonstrated that those with clinical improvement (n = 10) had higher
      serum concentrations of vitamin B12 and receptor-1 Vascular Endothelial Growth
      Factor before administration of ketamine. Ketamine infusion was well tolerated.
      CONCLUSIONS: The results confirm a rapid antidepressant effect of ketamine
      infusion maintaining for 2 weeks, in a considerable proportion of patients with
      bipolar depression, and good clinical tolerance of such procedure. Also, some
      clinical and biochemical factors associated with ketamine efficacy were shown.

PMID- 24946434
TI  - [Effectiveness of ketamine in depressed patients resistant to ECT or rTMS
      therapy].
AB  - OBJECTIVES: In the last decade several authors described a robust and clinically
      relevant alleviation of depressive symptoms after infusions of the uncompetitive
      N-methyl-D-aspartate (NMDA) glutamate receptor antagonist - ketamine. In the
      majority of published reports ketamine was administrated to patients with
      depression resistant to pharmacotherapy, but not to ECT. We present a series of 5
      subjects suffering from multimodal treatment-resistant depression (including ECT
      or rTMS and various medications) treated with intravenous infusions of ketamine
      in a subanesthetic dose of 0.5 mg/kg in the naturalistic setting. To the best of
      our knowledge it is the first report on ketamine infusion in patient resistant to
      antidepressants and r TMS METHODS: Two subjects have been diagnosed with MDD, one
      with BD, two with severe depressive episode. The efficacy and possible adverse
      events were monitored using psychometric scales. Basic life parameters and ECG
      were observed. RESULTS: Ketamine's infusions showed transient antidepressant
      efficacy. Improvement rate in our group was significant lower than in previously
      reported. Ketamine was generally well tolerated. We noted transient BP variations
      and appearance of mild and transient dissociative symptoms. Low early response
      rate may be correlated with resistance to previous multimodal treatment, high
      rate of somatization and anxiety comorbidity or heterogeneity of our group.
      CONCLUSIONS: Our findings do not support the use of ketamine infusions as the
      monotherapy in the subgroup of patients with multimodal treatment resistant
      depression.

PMID- 24946435
TI  - [Herbal remedies in depression--state of the art].
AB  - Recent decades have seen development of research and an increased interest in the
      psychopharmacology of natural remedies. More than 20 herbal remedies have been
      identified that may potentially be applied in medicine as antidepressive, anxiety
      relieving or sleep-inducing agents. Patients often prefer to take herbal remedies
      and often take them on their own, without consulting a physician. The aim of the
      study is to present the state of the art concerning the use of natural remedies
      in the treatment of depression. Following a literature review, 7 herbal remedies
      for which preclinical and clinical trials suggest their antidepressive influence
      have been identified: hypericum, lavender, borage, roseroot, chamomile, saffron
      and ginseng. For two of these, i.e. hypericum and saffron extracts,
      antidepressive effect in subjects with mild or moderate depression has been
      confirmed in controlled randomized clinical trials.

PMID- 24946436
TI  - [Does the usual dietary intake of patients with depression require vitamin
      mineral supplementation?].
AB  - INTRODUCTION: Research on diet and nutrition of patients with depression show
      that their eating habits are frequently irrational and result in the inconsistent
      supply of nutrients, especially vitamins and minerals, the deficiency of which
      leads to nervous system dysfunction. AIM: The aim of the study was to evaluate
      the content of selected vitamins and minerals in daily food rations of patients
      suffering from recurrent depressive disorders. METHODS: The study involved a
      group of 69 people (54 women and 15 men, aged 18-65 years, mean age of women 45.7
      +/- 12.2 years, men 46.0 +/- 12.2 years), treated for recurrent depressive
      disorders. A questionnaire designed in the Department of Dietetics and Clinical
      Nutrition, Medical University of Bialystok was used to collect dietary data. The
      quantitative assessment of eating habits used a 24-hour diet recall including 3
      weekdays and 1 weekend day. RESULTS: The study showed that the supply of most
      nutrients assessed was inconsistent with recommendations. CONCLUSIONS: The
      results indicate that the need for vitamin-mineral supplementation should be
      considered individually. Nutritional education related to the proper choice of
      groups of food products is indicated at the time of clinical improvement to
      ensure the optimum supply of vitamins and minerals.

PMID- 24946437
TI  - [The analysis of the polymorphic variations of the dopamine gen transporter
      (DAT1) and the serotonin transporter (5-HTTLPR) in patients with alcohol
      dependence syndrome with inclusion of the phenotypic feature of sweet liking
      preference].
AB  - OBJECTIVES: The purpose of this study was to determine the relationship between
      sweet-liking phenotype and the variation of the gene sequence of the dopaminergic
      and serotonergic system. METHODS: The study recruited 100 probands. The
      participants were interviewed for addiction (SSAGA-Semi Structured Assessment for
      the Genetics of Alcoholism) and assessed with the questionnaires: MMSE, Beck
      Depression Inventory and Hamilton Anxiety, Snaith-Hamilton Pleasure Scale. The
      taste was analyzed with tests to assess sensitivity to sweet taste and also smell
      tests were performed. Patients preferring the highest glucose volumes were called
      sweet likers. Statistical analyses were performed (SPSS- Statistical Package for
      the Social Sciences). RESULTS: Links between sweet liking phenotype and
      polymorphic variant of DAT1 gene were determined. The presence of DAT1 9/10
      genotype increased three fold time sweet liking phenotype (p = 0.015, odds ratio
      3.00), the presence of DAT1 10/10 decreased two fold time the chance being sweet
      liker (p = 0.051, odds ratio-0.43). Genotype 10/10 was significantly more common
      among sweet dislikers 10/10 (68.18% vs 47.92%) i 9/9 (6.82% vs 2.08%).
      CONCLUSIONS; A genetically significant association between the presence of 9/10
      DAT1 VNTR genotype and a sweet-liking phenotype in probands was determined.

PMID- 24946438
TI  - [Children sexual abuse in Poland--study of 257 sexual offenders against minors].
AB  - INTRODUCTION: Obtaining objective data on sexual offenders against minors is
      difficult. In order to enhance the possibilities to prevent such crimes it is
      essential to determine factors that condition this kind of sexual behavior. AIM:
      The aim of the study was to prepare a multidimensional analysis of a profile of
      sexual offenders against minors. MATERIAL AND METHOD: A detailed analysis of
      documentation from forensic sexological, psychiatric and psychological
      examinations and information from the records of the proceedings concerning 257
      perpetrators was performed by the authors. Information analyzed included
      demographic data, psychosocial background, psychosexual development, recent
      sexual activity, physical and mental health issues and information concerning
      accused sexual crime. RESULTS: The majority of the offenders had undisturbed
      family relations. However, subjects with sexual preference disorders perceived
      their parents' relationship as worse, reported more difficulties in educational
      process and in relation to teachers and peers. 5.4% of subjects experienced
      sexual abuse and 23.3% physical violence in their childhood. The majority
      reported no sexual dysfunction and had regular but rare sexual activity. 20.6%
      were diagnosed as having mental disorder and 36.8% were alcohol abusers. Almost
      30% were under influence of alcohol or another substance during the crime. The
      majority had no sexual preference disorder. Definite pedophilia was found in 27%
      and traits of psychosexual immaturity in 23.1% of cases. There was no
      relationship between sexual preference disorders and psychiatric comorbidity,
      alcohol or substance abuse. The acts of sexual abuse comprised genital touching,
      vaginal or oral intercourse as well as exposing offender's or victim's body.
      These acts were typically against one child, planned, being aware of victim's age
      and using physical violence. CONCLUSIONS: The data from our research should be
      taken into account when planning therapeutic and preventive interventions.

PMID- 24946439
TI  - [Pedophilia--a review of literature, casuistics, doubts].
AB  - The main purpose of this article is presentation of several basic issues related
      to the phenomenon of child sexual molesters and recognition of pedophilia as a
      significant social problem. The article, supplemented by casuistic illustration
      showing adolescents with sexual behavior disorders is giving rise to the
      following question: do they progress in their inappropriate behaviors to grow
      into adult molesters or do they stop anywhere along the way of their development?
      Casuistry, in the intention of the authors, is the background for discussion
      about prevention of child sexual abuse. This article presents also a review of
      the current knowledge about child sexual molesters. The topics include: the
      definition of pedophilia itself, which varies in the literature depending on the
      types of activities, kinds of victims and the circumstances in which the
      perpetrator acts, through to the recognition of symptoms of pedophilia as well as
      its consequences. It includes both intra-familial and extra-familial child sexual
      abuse and their offenders. The more, that the history of child sexual abuse is
      associated with numerous long-term physical, psychological, behavioral,
      interpersonal and social effects on the victim. The examinations made among
      pedophilic molesters have shown structural and functional temporal-limbic
      abnormalities, including abnormalities in the amygdala and it is possible that
      the pedophilic inclinations are secondary to neurodevelopmental perturbations and
      other neuropsychiatric syndromes.

PMID- 24946441
TI  - [Parameters of ante-mortem delirium].
AB  - OBJECTIVES: The aim of this study was to investigate the parameters of ante
      mortem delirium of the patients in a closed psychiatric institution and to
      compare them with the ante-mortem psychopathology of the medical patients.
      METHODS: There were 139 medical records of the patients analyzed, who died during
      the period of 1997-2003 at the in-patient psychiatric institution. The diagnoses
      were recorded according to the International Classification of Diseases, 10th
      Revision (ICD-10) criteria. Patients' data included age, gender, previous
      psychiatric disorders, current somatic and psychiatric morbidity, and
      comorbidity. RESULTS: The incidence of delirium was 83.7%. The delirium group
      included more elder, male persons who were more likely to have dementia and less
      inclined to depression. Surprisingly the incidence of delirium among non-dementia
      men was quite high--76.9%, as compared to non-dementia women--23.1% (P = 0.008).
      The duration of delirium differed from 1 to 1335 days. Longer delirium was
      observed among elder than 75 years (87.7, SD 183.9 vs 52.6, SD 121.4 days; P =
      0.019) and dementia (8.6, SD 173.6 vs 13.5, SD 11.6 days; P < 0.001) patients,
      but did not differ in gender groups. CONCLUSIONS: Ante-mortem delirium occurred
      more commonly in more elder and demented patients The duration of ante-mortem
      delirium was shorter in younger and non-dementia patients. Patients of the
      psychiatric institution tend to have longer deliriums than medical patients. The
      patients with depression and the history of alcohol abuse were not likely to get
      ante-mortem delirium. Before death in many persons hyperactive and mixed delirium
      transformed into hypoactive.

PMID- 24946440
TI  - [Gender identity disorders or andromimetic behaviour in a victim of incest--a
      case study].
AB  - Nowadays, it is becoming increasingly difficult to clearly classify the issues
      associated with the phenomenon of gender dysphoria due to the fact that one
      identifies oneself in the context of increasingly fluid categories of gender
      identity-- an intrinsic sense of being a woman or a man. The authors present a
      woman whose internal problems connected with her sexuality and incomplete
      identification with the role attributed to her gender originate from her family
      history. Long-lasting, traumatic experiences of incestuous abuse and violence on
      the part of close relatives disturbed her development in many areas of
      personality and functioning. The aim of the study was to verify the hypothesis of
      the existence of gender identity disorder accompanied by depressive disorders. In
      addition to the medical history, the study of patient's problems included the
      following diagnostic tools: the Minnesota Multiphasic Personality Inventory
      (MMPI) and the Rorschach Inkblot Test in a CSR Exner system (TPA). The study
      revealed that as for sexual identification, the patient unambiguously identifies
      herself as a woman. Her behaviour to become like a man does not deny her sex, or
      even involve a temporary need of belonging to the opposite sex. It should be
      interpreted in the broader context of her traumatic experiences, not just sexual,
      but also concerning different aspects of a female gender role.

PMID- 24946442
TI  - [Differences in effectiveness of intensive programs of treatment for neurotic and
      personality disorders. Is it worth to monitor the effectiveness of the
      therapeutic team?].
AB  - OBJECTIVES: To test whether three different intensive programs of treatment for
      neurotic and personality disorders are effective in decreasing neurotic symptoms
      and traits of neurotic personality and whether there are differences between them
      in clinical outcome. METHOD: The sample consisted of 105 patients (83% female,
      mean age 35) diagnosed with neurosis and personality disorders that were treated
      in three therapeutic wards under routine inpatient conditions. The therapeutic
      programs are designed for patients with neurotic and personality disorders. They
      consist of 6-12 weeks of approximately 5 hours of eclectic group treatment (group
      psychotherapy, psychodrama, psychoeducation etc.). Participants filled in
      Symptoms' Questionnaire KS-II, and Neurotic Personality Questionnaire KON-2006 at
      the beginning and at the end of the course of psychotherapy. RESULTS: The
      treatment proved to be effective in diminishing neurotic symptoms (d Cohen =
      0.56). More detailed analysis revealed that there was a significant interaction
      between the three analysed therapeutic wards and the effectiveness (12 = 0.09).
      The treatments offered in two institutions were effective (d Cohen = 0.80) while
      one of the programs did not lead to significant improvement of the patients. None
      of the therapeutic wards proved to be effective in changing the neurotic
      personality traits. CONCLUSIONS: There are significant differences in
      effectiveness of the intensive programs of treatment for neurotic and personality
      disorders. In the light of the literature, one can assume that the differences
      are more connected with the characteristics of therapeutic teams than with the
      methods used. The need for standard methods of effectiveness monitoring is
      discussed.

PMID- 24946443
TI  - [The influence of sociodemografic and medical variables on severity of anxiety
      and depressive symptoms during particular trimesters of pregnancy].
AB  - AIM: The aim of the study was to research the effect of selected socio
      demographic and medical variables on the severity of symptoms of anxiety and
      depression in different trimesters of pregnancy. MATERIALS AND METHODS: The study
      was prospective, longitudinal, the group consisted of 314 adult pregnant women.
      To assess the prevalence of depressive and anxiety symptoms the Hospital Anxiety
      and Depression Scale (HADS) was used. The results were statistically analyzed. To
      assess the normal distribution the Shapiro-Wilk test was used. Non-parametric
      tests: Mann Whitney U test and Kruskal Wallis ANOVA were used due to the
      distribution of the variables tested against the intergroup comparisons that
      deviate from the normal distribution. RESULTS: Only the assessment of the
      financial and housing situation given by the respondents was related to the
      severity of symptoms of anxiety and depression in the course of the entire
      pregnancy. The unmarried respondents had greater severity of depressive symptoms
      in the first and third trimesters. Other socio-demographic variables were not
      associated with the severity of symptoms of anxiety and depression in different
      trimesters of pregnancy. Medical variables (associated with an obstetric
      gynecological history), such as a history of miscarriage, complications in a
      previous pregnancy, the mode of delivery in a previous pregnancy, generally did
      not affect the severity of symptoms of anxiety and depression during pregnancy.
      Only major symptoms of depression during the third trimester were associated with
      complications in a previous pregnancy. An unplanned pregnancy turned out to be
      one of the most crucial variables determining higher severity of anxiety and
      depression during pregnancy. CONCLUSIONS: The knowledge of socio-demographic and
      medical factors associated with the severity of symptoms of anxiety and
      depression during pregnancy may facilitate better monitoring the groups of women
      being particularly vulnerable to the occurrence of these disorders. The
      introduction of screening tests regarding anxiety and depression during
      pregnancy, being carried out systematically in the course of pregnancy provides
      an opportunity for earlier diagnosis and more rapid implementation of good
      practice.

PMID- 24946445
TI  - [Maurycy Urstein: forgotten Polish contributor to German psychiatry].
AB  - Polish psychiatrist Maurycy Urstein (1872-1940) is nowadays almost forgotten. He
      is not mentioned in the history of Polish psychiatry which only partially may be
      explained by the fact that his most essential works were published in German
      language. His scientific oeuvre contains dozens of publications, including four
      monographs on catatonia. Urstein was an ardent advocate of the autointoxication
      theory of psychiatric disorders, fierce opponent of psychoanalysis and enthusiast
      of the use of biological methods of treatment in psychiatry. Both some eccentric
      views and specific personality probably equally contributed to his almost
      complete isolation among psychiatrists in the interwar Poland.

PMID- 24946444
TI  - [Creutzfeldt-Jakob disease in the psychiatric practice--case reports of the
      ataxic and Heidenhain variant].
AB  - OBJECTIVES: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare fatal
      neurodegenerative brain disorder of variable clinical manifestation. Making the
      right diagnosis still remains challenging. First symptoms are vague and differ
      between clinical subtypes of the disease. This is to present the symptoms
      variability and diagnostic difficulties in sCJD based on case reports of two
      female patients examined at time of the disease duration by psychiatrists.
      METHODS: Data of our patients were collected from hospital medical records.
      RESULTS: The case of patient A. P.' ataxic sCJD is an example of clinical picture
      suggesting neurological background of the disease almost from the symptoms' onset
      and being referred by psychiatrist to the neurological ward, where the right
      diagnosis of probable sCJD was established. In the opposite is the case of
      patient I. W.' Heidenhain variant of sCJD, misdiagnosed with dissociative
      disorder delivering huge diagnostic difficulties, even to neurologists. In both
      patients the certain diagnosis was confirmed at autopsy. CONCLUSIONS: In patients
      with visual disturbances of unknown etiology, even if the ophthalmological and
      neurological background is excluded, sCJD should be taken into consideration in
      the differential diagnosis.

PMID- 24946446
TI  - [Polish neuropsychiatric environment to sterilization laws in the thirties of the
      twentieth century].
AB  - The article describes the considerations that were carried out by Polish
      psychiatrists and neurologists in the thirties of the twentieth century, due to
      the sterilization of persons with mental disorders. The paper presents a short
      history of sterilization laws in the world. The reaction to the German Law for
      the Prevention of Hereditary Diseased Offspring (1933) among Polish psychiatrists
      was presented. The views of psychiatrists and neurologists to the proposed
      sterilization law in Poland were also outlined. Two projects of eugenic laws in
      Poland came from psychiatrists. Sterilization Law in Poland ultimately was
      enacted.

PMID- 24946447
TI  - Non-communicable diseases: clear and present danger.

PMID- 24946448
TI  - Predispositions of carcinoma of the breast: a review.
AB  - BACKGROUND: Breast cancer is an ancient disease and the leading malignancy
      affecting women. The incidence is high in developed countries while it is low but
      increasing in developing countries. The aim of this review is to update and
      summarize the predisposing factors of breast cancer. METHODS: Literature review
      was conducted using goggle search engine and hinari. Selected papers were taken
      for further reference and using books from author's collection. RESULTS: The
      cause of breast cancer is unknown but predisposing factors have been identified
      to indicate increase susceptibility to developing the disease. CONCLUSION: Breast
      is the commonest malignancy affecting women worldwide.

PMID- 24946450
TI  - Awareness of human immunodeficiency virus (HIV) infection among antenatal clients
      in Nnewi Nigeria.
AB  - OBJECTIVE: To determine the level of awareness of Human Immunodeficiency Virus
      (HIV) infection among antenatal clients in Nnewi Nigeria. SUBJECTS AND METHODS: A
      cross sectional descriptive study of six hundred consecutive antenatal clients
      attending the Nnamdi Azikiwe University Teaching Hospital and five private
      specialist hospitals (run by Consultant Obstetricians) in Nnewi was conducted
      over a six-month period (1st September 2008 -28th February 2009). Anonymous,
      structured, pretested questionnaire designed to assess the awareness of HIV
      infection was used. RESULTS: The mean age of all the 600 clients was 31.4 (SD
      2.8) years, majority were married (94%) and in the third trimester of pregnancy
      (69%). Most (58%) attended secondary school while 0.83% had no formal education.
      Only 2% had complete knowledge of the modes of HIV transmission while majority
      (96.5%) had partial knowledge. There was a statistically significant relationship
      between level of education and knowledge of HIV (p < 0.00001). HIV test was done
      on 419 (69.84%); 37 tested positive giving a seroprevalence rate of 8.83%. Among
      those tested, only 51.55% had counseling before testing. CONCLUSION: This study
      showed that the knowledge of HIV among women of child bearing age and the
      practice of voluntary counseling and testing are still poor in our environment.
      Improved public enlightenment and training of health workers are urgently needed.

PMID- 24946449
TI  - Premarital HIV testing on prospective couples in a teaching hospital in sub
      Saharan Africa.
AB  - BACKGROUND: Most religious bodies insist on premarital screening for prospective
      couples. AIM: To determine the level of voluntary screening, prevalence and risk
      factors of HIV among premarital couples. MATERIAL AND METHODS: A cross-sectional
      descriptive study using interviewer administered questionnaire and HIV screening
      to collect data. Systematic sampling of everythird premarital couples attending
      the General outpatient Clinic between November 2010 and October 2011. SPSS
      version 17 was used for data analysis of 386 subjects. RESULTS: A majority of
      respondents (83.4% or 322); X2 = 172.446, df = 1, p < .05) had knowledge of
      transmission of HIV. Mandatory HIV screening was 5.7% (22); X2 = 303.018, df = 1,
      p < .05), while voluntary testing was 30% (113). The sero-prevalence of HIV was
      2.6%, which was statistically and significantly associated with cohabitation and
      upper social class. A majority (68.4% or 266); X2 = 272.166, df = 3, p < .05)
      would call off marriage plans if their spouses tested positive to HIV. CONCLUSION
      The knowledge of transmission of HIV was very high with low sero-prevalence
      (2.6%) among premarital couples. Voluntary HIV testing was higher than mandatory
      request, while cohabitation and upper social class are risk factors for HIV
      transmission.

PMID- 24946451
TI  - Knowledge of obstetric danger signs amongst women of reproductive age in PATHS2
      Zaria cluster, Kaduna Nigeria.
AB  - BACKGROUND: The Partnership for Transforming Health Systems 2 (PATHS2) in Nigeria
      is implementing selected Behavior Change Communication (BCC) models to increase
      the knowledge of obstetric danger signs amongst women of reproductive age in
      Kaduna, Nigeria. The objective of this survey was to establish baseline
      proportions for knowledge of at least four danger signs of pregnancy, delivery
      and postpartum period respectively amongst women age 15-49, residing within 25
      selected communities in Zaria. METHOD: A cross-sectional survey was carried out
      amongst the eligible women within the communities. A pre-tested structured
      questionnaire was used for interview. RESULTS: 617 (94.5% response) eligible
      women participated in the study. Only 113 (18.31%) knew at least four danger
      signs during pregnancy. 61 (9.89%) knew at least four danger signs that can occur
      during labor and delivery and only 57 (9.24%) knew at least four danger signs
      that can occur during the postpartum period. CONCLUSION: A high proportion of the
      respondents are unaware of obstetric danger signs. It is recommended that radio
      broadcast be used as part of efforts towards increasing the proportion of women
      with knowledge of four or more obstetric danger signs in the study population.

PMID- 24946452
TI  - Self-reported adherence to treatment: a study of socioeconomic factors and
      psychiatric morbidity among male and female patients with HIV infection in
      Sokoto, Nigeria. Running title: Treatment adherence, socioeconomic factors and
      psychiatric morbidity in HIV patients.
AB  - OBJECTIVE: Adherence to treatment is important and relevant in HIV treatment.
      Previous studies in sub Sahara Africa and south western Nigeria reported that
      psychiatric morbidity influence treatment adherence. The present study was to
      examine treatment adherence among the male and the female patients with HIV
      infection and the effect of socioeconomic factors and psychiatric morbidity on
      treatment adherence. METHODS: A total of 159 patients which comprised of 48 male
      and 111 female who were eligible for this cross sectional prospective study were
      included having given their consent to participate. Questionnaire relating to
      socioeconomic factors and treatment adherence were administered. Psychiatric
      morbidity was assessed using HADS. Data was analyzed with SPSS for windows
      version 16.0. RESULTS: Treatment adherence was poor in 5.3% of the patients. The
      male patients had slightly better adherence than the female patients. Factors
      associated with poor treatment adherence include poor clinic attendance, presence
      of anxiety symptoms in males and poor education attainment in females.
      CONCLUSION: Treatment adherence is related to socioeconomic factors and
      psychiatric morbidity. Treatment protocol in which mental health and detailed
      socioeconomic circumstance of patient is an integral part should be encouraged.

PMID- 24946453
TI  - Seroprevalence of IgG antibodies to herpes simplex virus type-1 in Nigerian
      children.
AB  - BACKGROUND: Herpes simplex virus type-1 (HSV-1) can cause chronic ulcerative
      infection in immunosuppressed children leading to latency with subsequent
      reactivate in the conjunctiva resulting in scarring, thickening of the cornea and
      blindness. They are also common cause of fatal sporadic encephalitis in 70% of
      paediatric patients. This cross sectional study determined the prevalence of HSV
      1 in children in Kaduna State, Nigeria. METHOD: A total of 377 blood samples were
      collected from children less than five years old attending some selected
      hospitals in Kaduna State and analyzed for HSV-1 IgG antibodies employing Enzyme
      immune assaytechnique by using commercially available ELISA Kits. RESULTS: Sero
      prevalence rate of 57.8% (218/377) was obtained. The highest prevalence of HSV-1
      infection was obtained in children in age group 49-60 months (85.2%) and lowest
      in children in age group 13-24 months (44.8%). Further analysis of the result of
      children less than one year old showed that children 9-16 weeks old were more
      susceptible to HSV-1 infection. HSV-1 infection was significantly associated with
      age (X2 = 37.92, df = 4, p = 0.001). Though a higher prevalence was obtained in
      female children (61.5%) than male children (54.5%), the difference observed in
      the prevalence was not statistically significant (X2 = 1.84, df = 1, P = 0.105).
      HSV-1 infection was significantly associated with children who were in school (X2
      = 15.28, df = 1, P = 0.001) with a higher prevalence of 74.3%. CONCLUSION: Over
      half of the children sampled were protected from HSV-1 infection while 42.2% were
      susceptible to the infection and were at risk of developing severe HSV-1
      manifestation which includes keratitis, encephalitis and Keratoconjunctivitis.

PMID- 24946454
TI  - Pattern of bone tumours seen in a regional orthopaedic hospital in Nigeria.
AB  - BACKGROUND: Primary bone tumour is a challenge to Orthopaedic surgeons working in
      developing countries due to late presentation as a result of ignorance and
      poverty. This is further compounded by limited number of specialist personnel,
      diagnostic and therapeutic centres. Consequently, they are associated with high
      rate of morbidity and mortality, which can be reduced with early presentation.
      MATERIALS AND METHODS: This is a retrospective review of all histologically
      proven primary bone tumours seen at National Orthopaedic hospital Enugu, South
      east Nigeria, over a 6 year period. RESULTS: Sixty eight (68) cases met the study
      criteria and were reviewed. Male:Female ratio was 1.35:1, with a mean age of 22.8
      years and peak frequency in the 11-20 years age range. A total of 28 (41.1%) were
      benign, 21 (30.9%) were malignant while 19 (27.9%) were tumour-like conditions.
      The commonest benign tumour was osteochondroma, accounting for 44.7% of non
      malignant lesions, while fibrous dysplasia was the commonest tumour-like
      condition (23.4%). Primary malignant bone tumours accounted for 30.9% of all
      pathologies, with osteosarcoma (17) accounting for 80.1% of all malignant
      lesions. The commonest region affected is the leg i.e proximal tibia. Duration of
      symptoms before presentation ranged from 1 month to 12 years, with the commonest
      presenting complaint being a painless lump. CONCLUSION: Primary bone tumours is
      commonest in young males, usually benign and affecting the Tibia. Associated late
      presentation results in increased morbidity and mortality. Hence, efforts need to
      be geared towards public enlightenment in developing countries, to ensure early
      presentation, thereby reducing morbidity and mortality.

PMID- 24946455
TI  - Tuberculosis treatment outcomes and interruption among patients assessing DOTS
      regimen in a tertiary hospital in semi-urban area of south-western Nigeria.
AB  - BACKGROUND: Tuberculosis remains one of the most infectious diseases worldwide
      especially with the HIV pandemic. It is a cause of high morbidity and mortality
      in developing countries including Nigeria. Reasons contributing to high morbidity
      and mortality include high defaulting rate and treatment interruption. Several
      studies had evaluated the treatment outcome of tuberculosis but there is paucity
      of published literature on the outcome of treatment interruption especially in
      this environment. This study thus assessed the outcome of treatments and
      interruption among patients assessing DOTS regimen in a tertiary hospital located
      in asemi urban area in south-western Nigeria. METHODOLOGY: The study was a review
      of TB register of the federal medical centre, Owo from its inception in 2008 to
      2011. All the patients that have completed at least one course of chemotherapy
      (defined as 8 months of anti-tuberculosis treatment- 2 months intensive phase and
      6 months continuation phase) were included. Treatment outcome and interruption
      were defined in accordance with World Health Organisation (WHO) recommendations.
      Data were analysed with SPSS version 17. RESULTS: A total of 400 patients were
      included. The mean age of patients was 36.8 +/- 16.8 years and 56.3% were male.
      Majority, (79.7%) were adults aged 19-64 years, 12.5% were in the paediatric age
      group and 7.8% were elderly. Less than half, 45.3% had TB/HIV co-infection.
      Regarding treatment outcome of tuberculosis, 75.5% were cured, 14.8% died, 4%
      relapsed and 3% defaulted. A little above one-fifth, 21 (5.3%) had treatment
      interruption among whom 9 (42.9%) were successfully traced and completed
      treatment. Significantly, higher proportion of those that had treatment
      interruption died, 54.1% compared with their counterpart, 14.9%, (p < 0.001) and
      had relapse. (14.3% versus 3.4%, p = 0.01). CONCLUSION: A high rate of tracking
      failure among patients with treatment interruption was found in the study. In
      addition, mortality and morbidity were higher among patients with treatment
      interruption. A more concerted effort is needed in tracking/tracing patients with
      treatment interruption in orderto reduce morbidity and mortality among TB
      patients assessing treatment.

PMID- 24946456
TI  - The pattern of surgically treatable anorectal diseases in University of Port
      Harcourt Teaching Hospital, Rivers State, Nigeria.
AB  - INTRODUCTION: Disorders of the anus and rectum occurcommonly in surgical
      practice. Common anorectal disorders include haemorrhoids, carcinoma of the
      rectum, anal fissures, anorectal fistulae and abscesses. Less frequently
      encountered disorders include perineal injuries, anal cancers and rectal polyps.
      The purpose of this study is to determine the pattern of anorectal diseases which
      were surgically treated in University of Port Harcourt Teaching Hospital.
      PATIENTS AND METHODS: This is a 4 year retrospective study of all adult patients
      with anorectal diseases who were admitted into the surgical wards of University
      of Port Harcourt Teaching Hospital. Relevant data were retrieved and analyzed.
      RESULTS: One hundred and fifty cases were seen over the 4 year period. There were
      92 (61.33%) males and 58 (38.67%) females making a male to female ratio of 1.6:1.
      The peak age incidence was 31-40 years. The commonest anorectal disorder was
      haemorrhoids. Other commonly encountered conditions in decreasing order were
      carcinoma of the rectum, anorectal fistulae, anal fissures and rectal prolapsed.
      Five patients died and they all had carcinoma of the rectum. CONCLUSION:
      Haemorrhoids remain the commonest anorectal disorder in University of Port
      Harcourt Teaching Hospital. Carcinoma of the rectum which was not noted among the
      studied population in ourcentre 10 years ago now assumes the second position and
      this reflects an increasing incidence of the disease. Therefore, early diagnosis
      and treatment are imperative for increase in survival rate.

PMID- 24946457
TI  - Utilization of maternal health services in urban and rural communities of Anambra
      State, Nigeria.
AB  - OBJECTIVE: This study determined and compared the level and pattern of
      utilization of maternal services in urban and rural communities in Anambra State.
      DESIGN AND METHOD: A comparative cross-sectional study was carried out in two
      local government areas (LGA); Nnewi North (urban) and Dunukofia (rural). A total
      of 338 mothers of children aged 0-59 months in each of the two LGAs selected by
      multistage cluster sampling technique were studied. Data were collected using an
      interviewer administered questionnaire, analyzed and tests of significance
      performed with the p-value set at 0.05. RESULTS: Women in the rural area had
      higher fertility rate (t = 4.53, p < 0.05) and more children than their urban
      counterparts (t = 4.79, p < 0.05). The mean number of antenatal care (ANC) before
      delivery in urban and rural areas were 8.0 +/- 4.2 and 5.9 +/- 2.4 respectively
      and the difference was statistically significant (t = 7.52, p < 0.05). Half of
      the urban respondents delivered in private hospitals while 43.8% of rural
      respondents delivered in maternity homes. There was no significant difference in
      the pattern of post natal care utilization in both localities (chi2 = 0.695, p =
      0.405), as most of the women in both localities went for post natal consultation
      within 6 weeks of delivery. CONCLUSION: Measures to improve maternal health
      service utilization especially in rural areas should not only address the issue
      of access to care, but also improvement in quality of care and women empowerment.

PMID- 24946458
TI  - Taking the first step towards entrenching mental health in the workplace:
      insights from a pilot study among HR personnel in Nigeria.
AB  - BACKGROUND: The continued relevance of optimal employee mental health to
      sustainable human capital development in the workplace underscores the need to
      start harnessing all resources that can be mobilized to promote the entrenchment
      of workplace mental health. The strategic place of workplace Human Resource (HR)
      units in formulating and implementing workplace welfare schemes makes them
      potential partners. To actualize this, it is important to initially assess the
      preparedness of HR personnel for, and the possible barriers to entrenching mental
      health in the workplace. To suggest the initial course of action and to serve as
      a template for a robust large-scale study, we conduct a pilot assessment of the
      experience with, attitudes towards, and level of prioritization of mental health
      in the workplace among a cohort of HR personnel in Nigeria. METHODS: Participants
      were recruited in the course of a seminar/workshop and questionnaires were
      developed by authors to assess variables of interest. Attitudes were examined
      using an adapted form of the Link's Discrimination-Devaluation (LD-D) scale.
      RESULTS: A total of 90 human-resource personnel completed the questionnaires.
      Only 16% of the participants reported having handled the case of an employee with
      a suspected mental health problem in the preceding 2 years. Attitudes toward
      employees and prospective employees with mental illness were largely poor. For
      instance, more than 70% were likely to consider for employment someone with a pre
      existing physical disability than for someone with a history of mental illness.
      In terms of workplace health promotion priorities, physical health seminars took
      wide precedence over mental health seminars. CONCLUSION: The preliminary findings
      of this pilot study justify a need to conduct a large scale study. Significant
      challenges encountered in the course of this pilot study were highlighted while
      insights were drawn for the conduct of the main study/project.

PMID- 24946459
TI  - Pattern of cardiothoracic surgical diseases in a new cardiothoracic surgery unit
      in Nigeria.
AB  - BACKGROUND: Cardiothoracic surgical pathologies are available in all geographical
      regions of the world. Human and material resources are necessary for prompt
      diagnosis and proper treatment of these cases. METHODOLOGY: Retrospective
      analysis of cardiothoracic surgical cases in the first five years of our new
      cardiothoracic surgery unit was done. RESULTS: A total of 714 cases were seen
      during the study period with age range one month to 76 years with mean age of
      37.12 +/- 11.24 and male female ratio of 2:1. The yearly admissions from 2007 to
      2011 were 14%, 17%, 21%, 21% and 26% respectively. Cardiovascular diseases
      occurred in 22.30%, with 6% of children suffering from congenital heart defect
      and 6% of men suffering from acquired vascular disease. Surgical complications of
      pleuropulmonary tuberculosis occurred in 21.4% while thoracic trauma occurred in
      upto 21% of the patients. Aerodigestive tract foreign bodies were encountered in
      10.1% of cases and Pyogenic diseases occurred in 8.68%. Oesophageal lesions were
      diagnosed in 6.4% of the patients, pulmonary tumours including primary and
      secondary tumours were found in 4.3% while nontraumatic chest wall pathologies
      which included chest wall tumours, congenital deformities and chronic
      osteomyelities accounted for 3.2%. Mediastinal pathologies occurred in 0.98% and
      in the remaining 1.5% rare diseases were diagnosed such as third degree heart
      block, pulmonary embolism and thoracic endometriosis syndrome. CONCLUSION: This
      study shows that cardiothoracic surgical pathologies are common in our centre
      with predominance of thoracic pathologies, and therefore need to prioritize and
      ensure manpower development for treatment of all kinds of thoracic pathologies.

PMID- 24946460
TI  - Missed diagnosis of a delayed diaphragmatic hernia as intestinal obstruction: a
      case report.
AB  - Penetrating diaphragmatic injury rarely occurs in isolation. Diagnosis of
      traumatic diaphragmatic hernia resulting from penetrating diaphragmatic injury
      may be delayed or missed with attendant high morbidity and mortality. We reported
      a 28-year-old man who presented with features of subacute intestinal obstruction
      which became severe over the last four days. He had a stab injury to his left
      lower chest wall that was sutured 31/2 years prior to the development of
      symptoms. Emergency laparotomy with incidental findings of missed diaphragmatic
      hernia with gangrenous jejunal segment was found. The hernia was reduced,
      gangrenous segment resected with end to end anastomosis, and repair of
      diaphragmatic rent done. He had an uneventful recovery and follow up. There is
      the need to maintain high index of suspicion of Traumatic Diaphragmatic Hernia
      (TDH) in a patient with recent or previous thoraco-abdominal injury that will
      reduce the rate of missed or delayed diagnosis.

PMID- 24946461
TI  - Complete hydatidiform mole coexisting with a live fetus.
AB  - Hydatidiform mole co-existing with a normal fetus is very rare. We report a case
      of a 36 year old woman Para 4+0 who presented with amenorrhoea of twenty four
      weeks duration, vaginal bleeding, abdominal pain and pre-eclampsia. Ultrasound
      examination revealed a hydatidiform mole coexisting with a normal living fetus.
      The patient underwent a caesarean section at twenty eight weeks for maternal
      distress due to unbearable abdominal pain. The baby died after seven days. Post
      operatively she had an eclamptic fit and developed oliguria and persistent
      trophoblastic disease which were all successfully treated.

PMID- 24946463
TI  - Alternatives to withdrawal of services in the Nigerian health sector.

PMID- 24946462
TI  - Drainage of splenic abscess: a case report.
AB  - BACKGROUND: Splenic abscesses are uncommon manifestation of an acute abdomen. We
      reported a case of splenic abscess managed by tube drainage. METHOD: A case
      report using the case note records of the patient and review of the relevant
      literature on splenic abscess. RESULT: A forty five year old Nigerian who
      presented with features of splenic abscess and was managed by tube drainage. His
      post operative recovery was uneventful. CONCLUSION: Tube drainage of the splenic
      abscess is encouraged if there is easy access to the abscess and there is
      evidence of residual splenic tissue in the critically ill patient.

PMID- 24946464
TI  - [The influence of antipsychotic therapy on the cognitive functions of
      schizophrenic patients].
AB  - AIM: The aim of the present study was twofold: 1. to compare the efficacy of
      three antipsychotics (ziprasidone, olanzapine and perazine) in schizophrenia 2.
      to compare the improvement in cognitive functioning between groups treated with
      the three different neuroleptics. METHOD: A total of 58 Caucasian patients
      diagnosed with paranoid schizophrenia were recruited into the study group. We
      used the Polish version of the CIDI (Composite International Diagnostic
      Interview) to obtain ICD-10 diagnoses. The intensity of psychopathological
      symptoms was examined using the PANSS. The patients were randomly assigned to
      treatment with perazine, olanzapine or ziprasidone administered as monotherapy
      for 3 months. The treatment efficacy was measured as a change in the PANSS
      (Positive and Negative Syndrome Scale) total score from baseline (T0) to 3 months
      (T1). The WCST (The Wisconsin Card Sorting Test) was used to measure working
      memory and executive functions in the evaluated patients. Wilcoxon's and Kruskal
      Wallis tests were applied to compare changes in the PANSS scores between the
      treatment groups. To analyze the cognitive functions, Kruskal-Wallis test for the
      WCST parameters was used. RESULTS: The three antipsychotics similarly reduced the
      total PANSS score. The WCST parameters in the 3 groups of examined patients using
      the Kruskal-Wallis test revealed some differences between the three administered
      antipsychotics. CONCLUSIONS: Results suggest that the short-term efficacy of the
      atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs did
      not differ. Based on the analysis, a conclusion can be drawn that the three
      neuroleptics provided similar improvements in cognitive functioning.

PMID- 24946465
TI  - [Disturbances of emotional prosody in schizophrenia].
AB  - Disturbances in understanding and expression of emotional prosody of speech
      (aprosodia) belong to frequent but rarely described symptoms of schizophrenia,
      that negatively influence the life quality of patients. The role of prosody in
      the process of verbal communication is to complement and emphasize the language
      (linguistic prosody) and affective (emotional prosody) aspects of the spoken
      announcements. The authors review literature, including studies on functional
      brain imaging, and analyze profile and ground of the disturbances in the
      emotional prosody in patients with schizophrenia. Similarly to patients with
      damage to the right hemisphere, the speech of schizophrenia patients often is
      monotonous and deprived of emotional coloring, despite preserved experiencing of
      appropriate emotions, similarly to healthy subjects. In the acoustic speech
      analysis of patients with schizophrenic psychosis, reduced fundamental frequency
      of the utterance, clinically defined as aprosodia, was showed. It was noticed
      that the problems in identifying emotions concern mainly negative emotions and
      that bigger defects were demonstrated by men. The authors emphasize the need to
      recognize and include appropriate therapeutic treatments in prosody disturbances,
      which aim is to improve the well-being and social functioning of the patients.

PMID- 24946466
TI  - [Between health and schizophrenia].
AB  - The article, based on the literature review, presents actual concerns on
      prognosis and opportunity to achieve recovery in persons with schizophrenia.
      Catamnestic long-term studies published during last decades more often indicated
      a favorable course of schizophrenia than it was in the past. One explanation may
      be the progress in pharmacotherapy, which allows the achievement of a better
      outcome in the treatment. On the other hand, the researchers have been committed
      to more detailed studies on the course of schizophrenia by more frequently
      repeated public testimonials of the ill persons, which forced the prognosis to be
      more optimistic. A good example is the discussion about the recovery in
      schizophrenia and the change in perception of the disease, despite differences in
      the attitudes between clinicians and patients. Seeing the opportunity to conduct
      a normal life in spite of serious mental disease is challenging for patients and
      their relatives, as well for psychiatrists and therapists. It motivates to
      overcome the limitations that the disease brings and the barriers in society.

PMID- 24946467
TI  - [Mineralization of the basal ganglia as the supposed cause of poor tolerance of
      zuclopenthixol in a patient with long-term untreated paranoid schizophrenia].
AB  - Formations described as intracranial calcifications can appear in the course of
      diseases of the central nervous system, other systems and organs (e.g.
      endocrine), but also as a disorder of idiopathic character. They are frequently
      located in subcortical nuclei and usually constitute an incidental finding. This
      report presents the case of a patient suffering from paranoid schizophrenia for
      approximately 40 years, who did not agree to any treatment and was hospitalized
      against her will because she was the threat to the lives of others. She was
      treated with zuklopentixol resulting in positive symptoms reduction and
      considerable improvement in social functioning. Unfortunately neurological
      symptoms appeared: bradykinesis, rigidity--of the type of the lead pipe, balance,
      posture and gait abnormalities, disturbances in precise hands movements, double
      sided Rossolimo's sign, plantar reflex without the participation of the big toe
      on the left. Neuroimaging studies have demonstrated changes in the form of
      lenticular nuclei calcification and reduction of signal intensity in posterior
      parts of both putamens. Neurological symptoms decreased significantly after
      switching to atypical neuroleptic (olanzapine), and the patient did not require
      any additional treatment. Mineralization of the basal ganglia can often be
      associated with psychiatric disorders and it shouldn't be neglected because it
      can require modification of pharmacotherapy or additional neurological treatment.

PMID- 24946468
TI  - [Augmentation of antipsychotics with glycine may ameliorate depressive and
      extrapyramidal symptoms in schizophrenic patients--a preliminary 10-week open
      label study].
AB  - AIM: The objective of this study was to analyze the changes in depressive and
      extrapyramidal symptomatology during glycine augmentation of antipsychotic
      treatment in patients with schizophrenia. MATERIALS AND METHODS: Twenty-nine
      schizophrenic patients (ICD-10) with predominant negative symptoms in stable
      mental state participated in a 10-week open-label prospective study. Patients
      received stable doses of antipsychotic drugs for at least 3 months before glycine
      application. During the next 6 weeks patients received augmentation of
      antipsychotic treatment with glycine (up to 60 g per day). The first and last two
      weeks of observation were used to assess stability of mental state. Symptom
      severity was assessed using the Hamilton Depression Rating Scale (HDRS), the
      Positive and Negative Syndrome Scale (PANSS), and the Simpson-Angus
      Extrapyramidal Symptom Rating Scale (SAS). RESULTS: In the studied group after 6
      weeks of administration ofglycine a significant improvement in depressive
      symptoms (reduced scores by 25.8% in HDRS, p < 0.001) and reduced scoring in mood
      symptoms of PANSS were observed. In SAS a reduction of extrapyramidal symptoms'
      severity (p < 0.05) was also noted. Two weeks after the glycine augmentation the
      symptom severity in the HDRS, PANSS, and SAS remained at similar levels.
      CONCLUSIONS: Glycine augmentation of antipsychotic treatment may reduce the
      severity of depressive and extrapyramidal symptoms. Glycine use was safe and well
      tolerated.

PMID- 24946469
TI  - [The newest therapeutic directions in the rehabilitation of patients with mental
      disorders].
AB  - In this paper, the authors attempted to present the comprehensive literature
      review on the newest therapeutic interventions such as cognitive remediation
      therapy (CRT), mindfulness-based cognitive therapy (MBCT), social cognition and
      interaction training (SCIT), and acceptance and commitment therapy (ACT) which
      appeared promising whilst their implementing among schizophrenic patients,
      patients with anxiety disorders, eating disorders, and affective disorders. In
      the presented work particular attention was focused on two kinds of
      psychotherapeutic interventions: social cognitive trainings and cognitive
      remediation therapy (CRT) and their effectiveness in the rehabilitation process
      of schizophrenic patients. The growing body of research based on application of
      the above mentioned techniques in psychiatric population gives remarkable hope to
      improve quality of cognitive and psychosocial therapeutic interventions and to
      set up both complex and comprehensive therapeutic programme for patients with
      mental disorders.

PMID- 24946470
TI  - [The affective disorder-related burden imposed on the family environment--an
      overview].
AB  - The family burden (FB) has been defined as a multidimensional impact imposed by
      an illness on caregivers. FB can be divided into objective (i.e. related to
      measurable problems) and subjective one (i.e. related to caregivers' emotions
      arising in response to objective difficulties). FB is known to be related to
      disturbances in the functioning of the family system, higher level of stress, and
      the presence of financial problems. Some gender-dependent differences in the
      characteristics of FB have been found. Since family member's illness can be not
      only a ballast, but also a potential source of satisfaction, it has been found
      that the level of caregiving-related satisfaction is a significant predictor of
      FB severity. FB dynamics does not seem to be parallel to the course of illness.
      Problem-focused and task-focused coping strategies are known to be related to
      lower values of FB. There is evidence suggesting that in families of patients
      with BD depressive episodes trigger substantially higher severity of FB, as
      compared to manic episodes. Data on FB related to major depressive disorder (MDD)
      are scarce. Assertive community treatment strategies are the main option of
      reducing FB in the context of affective disorders, yet data on their
      effectiveness are inconclusive.

PMID- 24946471
TI  - [No association of glucocorticoid receptor gene polymorphism (rs6190) with
      unipolar and bipolar disorder].
AB  - AIM: Functional polymorphism ER22/23EK glucocorticoid receptor leads to reduction
      of its resistance and to increase in its sensitivity to the glucocorticoid that
      regulate the functioning of the axis hypothalamus - pituitary - adrenal glands.
      Disturbances in the regulation of this axis are observed in patients with
      psychiatric disorders. The aim of this study was to demonstrate the association
      ER22/23EK polymorphism with bipolar disorder and major depressive disorders.
      METHODS: In the study 144 patients with unipolar disorders and 479 patients with
      bipolar disorder were included. Patients were diagnosed by two psychiatrists on
      the basis of medical records and interview based on SCID criteria (Structured
      Clinical Interview for DSM Disorders). The control group comprised 595 healthy
      subjects. As the research material peripheral blood was used, from which DNA was
      obtained. Genotyping was performed using PCR - RFLP method. RESULTS: No
      association of ER22/23EK polymorphism with unipolar disorder or with bipolar
      disorder was found. GA genotype was not observed in any of the subjects.
      CONCLUSION: ER22/23EK functional polymorphism of the glucocorticoid receptor gene
      is not associated with unipolar and bipolar disorder.

PMID- 24946472
TI  - [Fatty acids in treatment and prevention of depression].
AB  - The increase of incident rates for depression and other psychiatric disorders is
      a serious threat for all communities. The study presents data verifying the
      relationship between the level of omega-3 PUFAs in the blood and an increased
      risk of depression, including the parallel standard therapy with antidepressants
      or not. There is an increasing number of evidences that fatty acids like DHA, AA
      and EPA are linked to depression. In epidemiological studies and clinical trials
      a correlation between the decline of omega-3 PUFA intake and an increasing risk
      for developing depression is considered.

PMID- 24946473
TI  - [The Machiavellianism and manipulation tactics used by patients with borderline
      personality disorder in everyday life and in therapy].
AB  - AIM: The aim of the researches was to inspect the relation between borderline
      personality and Machiavellianism as well as the tendency to apply various
      manipulation tactics in everyday life and in therapy. METHOD: The test used an
      original/authors' survey for testing the tendency to employ manipulation tactics
      as well as a MACH-IV questionnaire (Christie, Geis, 1970) for measuring
      Machiavellianism. The studied group included 30 patients with diagnosed BPD, 37
      therapists and 30 persons in the control group. RESULTS: No differences were
      noted in the general indicator of Machiavellianism; however, the patients scored
      lower on the Tactics scale than people from the control group. Patients preferred
      employing the tactics of taking offense, lying and begging in everyday life.
      Compared to people from the control group, patients presented a larger tendency
      to employ tactics of begging, threatening and threatening to break off a close
      relationship, and a lower tendency to employ seduction. According to therapists,
      during the therapy patients most often resorted to lying and arousing guilt.
      Therapists assessed the patients' tendency to employ manipulation tactics higher
      than the patients themselves. CONCLUSIONS: BPD patients are characterized by a
      degree of Machiavellianism similar to that present in people from the control
      group. Patients show larger tendency to employ tactics of threatening and begging
      than the people from the control group. Compared to assessments made by doctors
      and therapists, they lower their own assessment of the tendency to employ
      manipulation. The longer the seniority of therapists and the larger the number of
      treated BPD patients, the higher the ability to perceive the patients' tendency
      to manipulate.

PMID- 24946474
TI  - [Polish adaptation and validation of the Agoraphobic Cognitions Questionnaire and
      the Body Sensations Questionnaire].
AB  - AIM: The present study aimed at the adaptation and validation of two
      questionnaires assessing fear of bodily sensations (BSQ; suggested Polish name:
      Kwestionariusz Doznan Cielesnych [KDC]) and concerns specific to agoraphobics
      (ACQ; suggested Polish name: Kwestionariusz Mysli Towarzyszacych Agorafobii
      [KMTA]). METHOD: The study included a total of 82 patients diagnosed with
      agoraphobia or panic disorder with agoraphobia according to the diagnostic
      criteria of the DSM-IV as well as 100 control subjects who did not show the
      presence of mental disorders. RESULTS: The results showed that both adapted
      questionnaires meet basic psychometric criteria. The Polish-language versions of
      the ACQ and BSQ are characterized by a high content validity, internal
      consistency and showed to be stable over a period of 28 days. Moreover, the
      factor structure of the Polish version of the ACQ showed to be highly similar to
      the original version. CONCLUSIONS: Polish-language versions of the ACQ and BSQ
      have been found to be reliable and valid research and diagnostic instruments for
      the assessment of fear for bodily sensations and agoraphobic cognitions. Due to
      their high efficiency and adequate psychometric characteristics these measures
      might be very useful in research as well as in the diagnosis and evaluation of
      therapeutic effects.

PMID- 24946475
TI  - [Social Avoidance and Distress Scale (SAD) and Fear of Negative Evaluation Scale
      (FNE)--reliability and the preliminary assessment of validity].
AB  - AIM: Assessment of reliability, cross-validity and usefulness in everyday
      clinical practice of two related tools: Social Avoidance and Distress Scale (SAD)
      and Fear of Negative Evaluation Scale (FNE). MATERIAL AND METHOD: Analysis of
      tests results of 453 females and 172 males diagnosed in the years 2008-2010 in
      the Outpatient Clinic for Neurotic and Behavioral Disorders of the Cracow
      University Hospital, including, inter alia, results of the questionnaires SAD and
      FNE. The scales have been, with the consent of their authors (R. Friend) and the
      copyright holder (APA), translated into Polish and back-translated. Subjects also
      completed the symptom checklist KO '0'(n = 512), and neurotic personality
      questionnaire KON-2006 (n = 505), as well as the NEO-PI-R personality inventory
      (n = 46). The reliability and cross-validity coefficients of Polish versions were
      assessed in the patient population and their results were compared with those of
      the group of 75 medical students. RESULTS: The translation was verified by
      retranslation. The reliability coefficients of Polish version of the SAD and FNE
      scales turned out to be high--Cronbach's alpha coefficient was 0.94 for both
      scales, Guttman's split-half reliability coefficient 0.93. Correlations with
      symptom checklist KO '0 'and neurotic personality questionnaire KON-2006, as well
      as with the NEO -PI-R personality inventory were significant and indicate a good
      cross-validity of the analyzed tools. The average results in the patient
      population for both scales were significantly higher than the results in the
      preliminary control group of medical students. CONCLUSIONS: Polish versions of
      SAD and FNE questionnaires, like their other translations from English, proved to
      be reliable and have a high cross-validity with other original Polish tools used
      in the diagnosis of neurotic disorders, which allows to recommend them to be used
      in further studies, also in comparing healthy persons with those suffering from a
      variety of neurotic disorders.

PMID- 24946476
TI  - [Quality of Life in Depression Scale (QLDS)--development of the scale and Polish
      adaptation].
AB  - AIM: The aim of this study was to adapt the Quality of Life in Depression Scale
      to Polish conditions. The scale determines the quality of life, defined in terms
      of the concept of needs, and focuses on patients with depressive disorders. Since
      its basic version has been developed, the tool was adapted in many countries,
      also outside Europe. METHOD: The adaptation procedure included the translation of
      the original version into Polish, followed by the English retranslation, and was
      performed by four independent, qualified translators. The final Polish version
      was verified during a pilot study. RESULTS: This pilot study confirmed high
      reliability of the Polish version of Quality of Life in Depression Scale.
      CONCLUSION: The Quality of Life in Depression Scale (QLDS) can be considered an
      interesting tool in view of its broad theoretical background, and a simple
      procedure to complete during a clinical evaluation. The use of a specialist
      translation procedure, and the results of our pilot study suggest that the QLDS
      can be used in further research, both when evaluating a clinical population and
      when dealing with individual patients.

PMID- 24946478
TI  - [Impulsivity in sexual offenders--new ideas or back to basics?].
AB  - Despite the fact that the group of sexual offenders remains a population which is
      still difficult to study, the results of current research are considered novel
      and interesting. Surprisingly, the very old descriptions applying to paraphilia,
      which is considered to be one of the reasons of sexual offences, appear to be
      accurate, especially in the context of similarities between impulsivity and
      pathologic sexual behaviors. Notably, the nomenclature concerning impulsivity
      enables a specific and reasonable description of behaviors associated with sexual
      offences. Moreover, the results of research studies show that it is the lack of
      inhibition, not pathologic arousal, which is the most important factor in the
      pathogenesis of forbidden sexual behaviors. In addition, it has been shown that
      behavioral manifestations of impulsivity (substance abuse, suicide attempts)
      appear commonly in sexual offenders. Mutual relationships between alcohol
      drinking, suicide attempts, history of child sexual abuse and sexual offences,
      both in symptomatologic and etiologic aspect, raise a suggestion that all these
      phenomena may share a common background of poor inhibitory control.

PMID- 24946477
TI  - [Discontinuation-Emergent Signs and Symptoms Inventory--Polish translation of the
      discontinuation signs and symptoms checklist].
AB  - A number of preclinical and clinical studies are focused on mechanisms of SSRI
      discontinuation syndrome as well as the patient populations and agents that are
      most affected by this phenomenon. Characteristics of onset, duration, and
      severity of any discontinuation symptoms and spontaneous reports of
      taper/poststudy-emergent adverse events should be compared with those of the
      active comparator in these studies. Besides, common clinical practice supplies a
      number of problems associated with SSRI discontinuation syndrome as related to
      treatment planning and management. The recommended instrument for evaluating SSRI
      discontinuation syndrome symptoms is the Discontinuation-Emergent Signs and
      Symptoms (DESS) inventory. DESS is a 43-item checklist that can be administered
      in a clinician-rated form, a self-rated form, or an interactive voice-response
      form. The paper presents the Polish version of DESS inventory along with its
      application and interpretation instructions. DESS inventory is of substantial
      advance in common psychiatric practice as it enables effective SSRI
      discontinuation management on drug tapering and in case of the non-compliance
      with the treatment. Its use in the systematic studies facilitates conclusive
      outcome results and is of prime importance as being comparable with literature
      outcomes.

PMID- 24946479
TI  - [Swedish medical research does not need more control].

PMID- 24946480
TI  - [Yet another polio type gone].

PMID- 24946481
TI  - [Regular self-weighing is good for keeping the weight. Swedish men increases in
      average 15 kg between enrollment and age 40].

PMID- 24946482
TI  - [2,4-dinitrophenol--a lethal weight reducing agent].

PMID- 24946483
TI  - [Relatives' efforts after stroke are substantial and often lifelong. Survey study
      shows that the consequences for relatives need more attention].

PMID- 24946484
TI  - [From pediatric to adult clinic through a transition clinic. Experiences of HIV
      infected young people who have been ill all their lives].

PMID- 24946485
TI  - [Diabetic ophthalmology in transition: the importance of a sample].

PMID- 24946486
TI  - [Shoulder fractures, part 2: Scapular and proximal humerus fractures].

PMID- 24946487
TI  - [Cheaper with biosimilars, but safety comes first].

PMID- 24946488
TI  - [Health care must become better detecting elder abuse].

PMID- 24946489
TI  - [Dissatisfied primary care patients in vulnerable areas goes to the hospital
      emergency department].

PMID- 24946490
TI  - [The American civil war resulted in a boost for healthcare].

PMID- 24946491
TI  - [Medication review is a task for the physician].

PMID- 24946492
TI  - [Let us avoid introducing a "lex Gard" in health care].

PMID- 24946493
TI  - [Swedish universities need to invest more in education. Two American high-ranking
      universities and two Swedish compared in report from the Centre for Business and
      Policy Studies].

PMID- 24946494
TI  - [Time for a modern approach to osteoarthritis].

PMID- 24946495
TI  - [Osteoarthritis increasingly common public disease].

PMID- 24946496
TI  - [Possible connection between osteoarthritis and cardiovascular disease].

PMID- 24946497
TI  - [Osteoarthritis after serious joint damage--great need for more studies].

PMID- 24946498
TI  - [Primary health care plays a key role in early diagnosis and follow-up].

PMID- 24946499
TI  - [Exercise is a cornerstone in the treatment].

PMID- 24946501
TI  - [Lack of structure and fragmentation of responsibilities makes it difficult to
      aquire a Swedish medical license].

PMID- 24946500
TI  - [Better management of OsteoArthritis, BOA].

PMID- 24946502
TI  - [Alcohol addiction in itself is not a reason to suspend the driving license].

PMID- 24946503
TI  - [Reply from the Swedish Transport Agency: Medical requirements for the driving
      license is a difficult and important issue].

PMID- 24946504
TI  - [Time to discover noninvasive pulse wave analysis].

PMID- 24946505
TI  - [Congratulations 2-year-old--you have been published!].

PMID- 24946506
TI  - Applying ethical principles to international community-based research: a case
      study from the Consortium to Respond Effectively to the AIDS-TB Epidemic (CREATE)
      .

PMID- 24946507
TI  - Consent for nondiagnostic research biopsies: a pilot study of participant recall
      and therapeutic orientation.

PMID- 24946508
TI  - Determining minimal risk for comparative effectiveness research.

PMID- 24946509
TI  - Negligence and embryo protection: a new frontier for medical law?
AB  - In early 2012, many embryos were destroyed in a Roman hospital because of the
      breakdown of the freezing machine. In such cases the biological damage, for
      instance by ovarian hyperstimulation, and the pecuniary damage, i.e. the costs of
      treatments, can be compensated if the plaintiff demonstrates that subsequent
      fertility treatments would not have been performed if the embryos had not been
      destroyed. The damage for pain and suffering can be compensated regardless of
      what would have been the outcome of the implant. Indeed, even in the case where
      the implant of cryopreserved embryos would not have been successful, the loss of
      embryos is suitable to cause pain and suffering because it violates the right to
      become a parent. Nevertheless, the proof of such damage is difficult to achieve.
      In order to impede that the negligent loss of embryos would remain without
      consequences it seems to be possible and appropriate to provide a crime to punish
      those who cause the death of embryos by negligence.

PMID- 24946510
TI  - I'm getting turned off: emerging consensus on deactivating cardiac implantable
      electronic devices.
AB  - The surgical insertion of permanent heart rhythm (resynchronization) devices
      within individuals who have chronic cardiac deficiencies is widespread and
      increasing. It is predictable that some individuals who have had a permanent
      heart rhythm device implanted will subsequently reach a point, physically and/or
      emotionally, at which they (or their surrogates) indicate the desire that their
      own resynchronization be removed or deactivated. Despite continuing controversy,
      a professional international consensus has begun to emerge over the past few
      years, concerning the fundamental legal and ethical principles that ought to
      guide clinical practice regarding the deactivation of cardiac implantable
      electrical devices (CIEDs). The central legal and ethical principles of the
      emerging professional consensus in this sphere are briefly summarized in this
      article, along with some thoughts about the challenges of translating those
      principles into clinical practice for specific patients.

PMID- 24946511
TI  - The historical development of health care law and bioethics in England and Wales:
      a symbiotic relationship?
AB  - The paper explores the backward and forward linkage between HCL and bioethics.
      Indeed, the relationship between the two is so close that it can be considered
      one of symbiosis. This is particularly the case when an account is taken of how
      HCL and bioethics positively benefitted from each other in diverse ways during
      their development into their present status as discrete disciplines. In the first
      place, the aftermath of the Second World War, such as the Nuremberg trial and
      unprecedented medical experiment scandals in the 1960s/70s fuelled the increasing
      participation of lay scholars in exploring and critiquing medical ethics which
      culminated in the emergence ofbioethics.2 This in turn facilitated the evolution
      of HCL as a discipline, since academic lawyers involved in early bioethical
      discourse developed interest in exploring the interface between law and bioethics
      at the same time that society was waking up to the ethical implications of
      medical advances. As HCL emerged as a discrete discipline, it consolidated the
      status of bioethics as a field of inquiry by projecting the relevance of the
      latter in adjudication of novel cases with significant slippery moral undertones.
      Thus, the chicken and egg paradox finds a perfect reflection in the emergence of
      health care law and bioethics in England and Wales.

PMID- 24946512
TI  - Medicine, law and human rights - a symbiotic relationship.
AB  - Law and medicine are separate professions, and attorneys and physicians often see
      their professions in conflict. There are, however, more similarities than
      differences between the two professions. And there are areas of mutual concern
      and overlap that demand the application of both legal and medical knowledge for
      the good of the society. In the new categorical system of values, which is
      substantially influenced by the so-called modern or aggressive medicine, clever
      physicians, researchers, and technicians discover newer and better ways to do
      things. Often, what science and technology make possible soon becomes permissible
      and, eventually, normal and expected. Given the rapid advances in technology and
      medical technology in particular, it is clear that without the reasonable
      restraints imposed by philosophical but also, legal critique, medicine and its
      practitioners may unintentionally convert science and medical method into a
      muddled philosophy of human life'. Against this background, this paper will
      handle the questions posed by the extent and protection of human rights and
      freedoms in terms of application of new biomedical techniques and technologies of
      treatment toward the development of International human rights law. It also
      discusses the compatibility of domestic medical law with the normative system of
      international human rights.

PMID- 24946514
TI  - [Metabolic surgery].

PMID- 24946515
TI  - [Insured medical care committee-role and future-].

PMID- 24946516
TI  - [State of the lung cancer treatment].

PMID- 24946513
TI  - Perceptions of people living with HIV/AIDS regarding access to health care.
AB  - Although the health care is replete with technology in the present day, it is not
      freely accessible in a developing country. The situation could be even more
      compromised in the case of people living with HIV/AIDS, with the added dimension
      of stigma and discrimination. What are the factors that act as barriers to health
      care? This study was conducted to look into perceptions of people living with
      HIV/AIDS with regard to access to health care. The study looked into
      accessibility of general health vis-a-vis access to antiretroviral therapy.
      Demographic variables like age, gender, income were studied in relation to
      factors such as counseling, confidentiality, stigma and discrimination, which are
      known to influence access to health care. People living with HIV/AIDS perceive
      general health care as more accessible than care for HIV treatment.
      Discrimination by health care workers causes a barrier to accessibility.

PMID- 24946517
TI  - [Neoadjuvant chemo (chemoradio) therapy for advanced non-small cell lung cancer].
AB  - Although there has been considerable progress in new-generation cytotoxic agents
      and radiotherapy techniques, surgery is still one of the best potentially
      curative therapeutic options for non-small cell lung cancer (NSCLC). For locally
      advanced NSCLC patients, the recommended treatment is platinum-based chemotherapy
      or chemoradiotherapy if possible. If surgery becomes feasible after suitable
      chemoradiotherapy, the long-term survival of such patients is improved. Although
      the evidence level for induction chemo (chemoradio) therapy is low, the
      incorporation of chemotherapy, radiotherapy, and surgery will greatly impact the
      strategy of future lung cancer treatment.

PMID- 24946518
TI  - [Current status of postoperative adjuvant chemotherapy for completely resected
      non-small lung cancer].
AB  - Multiple, large, randomized trials assessing the efficacy of adjuvant
      chemotherapy for resected non-small cell lung cancer (NSCLC) have been reported
      in recent years. Three of six trials involving 300 or more patients with early
      stage NSCLC demonstrated that adjuvant cisplatin-based chemotherapy can
      significantly improve 5-year survival in carefully selected patients with
      resected NSCLC. These benefits were confirmed in a meta-analysis of modern
      cisplatin-based adjuvant trials. The most consistent benefit was reported in
      patients with resected stage II and IIIA NSCLC. On the other hand, studies from
      Japan reported that adjuvant therapy with uracil-tegafur (UFT) afforded an
      improvement of 4% in the 5-year survival rate and a relative risk reduction of
      26% in mortality at 5 years among patients with T1-2N0 (stage I) disease. In
      particular, the Japan Lung Cancer Research Group demonstrated an improvement in
      the 5-year survival rate of 11%, favoring chemotherapy with UFT in the subset of
      patients with T2N0 (stage IB) disease. Two published meta-analyses based on
      abstracts estimated a relative risk reduction in mortality of 11-13% at 5 years.
      Thus, the information currently available supports the administration of adjuvant
      chemotherapy for patients who have undergone complete resection of stages IB-IIIA
      NSCLC. The recent results of biological research indicate that the expression of
      some tumor markers including ERCC1 should be evaluated to determine which
      patients are more likely to benefit from chemotherapy. The next advance will be
      to identify the subsets of patients who will derive the greatest benefit from
      adjuvant chemotherapy.

PMID- 24946519
TI  - [Development of molecular targeted therapies in lung cancers].
AB  - Human cancers usually possess cumulative genetic aberrations. However, recent
      studies have revealed that the proliferation and survival of specific subsets of
      lung cancer depend on a few somatic mutation(s), so-called driver mutations.
      Representative driver mutations include the EGFR mutation and ALK translocation
      identified in about 40% and 3% of lung adenocarcinomas in Japan, respectively.
      These tumors are extremely sensitive to the respective tyrosine kinase
      inhibitors. This sensitivity has encouraged researchers and clinicians to explore
      novel driver mutations in lung cancers as future molecular targets. Driver
      mutations reported so far include the HER2 mutation, BRAF mutation, ROS1
      translocation, RET translocation, and NTRK translocation in lung adenocarcinomas,
      and FGFR1 amplification, DDR2 mutation, and FGFR3 translocation in lung squamous
      cell carcinomas. However, despite initial dramatic responses, the acquisition of
      resistance to molecular targeted drugs is almost inevitable. Overcoming
      resistance to molecular targeted drugs, the key drugs at this time, is an urgent
      issue to improve the outcomes of lung cancer patients.

PMID- 24946520
TI  - [Radical segmentectomy].
AB  - Sublobar resection, which consists of segmentectomy and wedge resection, for the
      radical treatment of small-sized non-small cell lung cancer (NSCLC) in patients
      able to withstand lobectomy remains controversial. The dogma that lobectomy is
      the standard of care for NSCLC has been upheld until recently, although several
      current investigations, mostly from Japan, found equivalent outcomes of sublobar
      resection and lobectomy for T1a NSCLC. The current understanding of radical
      segmentectomy can be summarized as follows. First, the indications for
      segmentectomy should be limited to T1 tumors < or = 3cm in diameter, and high
      resolution computed tomography (CT) and positron emission tomography-CT findings
      must be taken into consideration, particularly for T1b tumors. Whenever nodal
      involvement or an insufficient margin is confirmed intraoperatively,
      segmentectomy should be converted to lobectomy with complete nodal dissection.
      Second, radical and compromising indications for segmentectomy must be
      independently discussed. The former is for low-risk patients who can tolerate
      lobectomy. Third, segmentectomy is more valuable than wedge resection from an
      oncological perspective because it allows nodal dissection at the hilum. Thus,
      the choice of the most suitable procedure, such as whether to convert
      intraoperatively to lobectomy, should consider precise staging and the lower rate
      of local recurrence resulting from sufficient surgical margins. Therefore,
      segmentectomy must be clearly separated from wedge resection among the categories
      of sublobar resection for lung cancer. Surgeons must become adept at and master
      segmentectomy as a keynote procedure because small lung cancers are being
      detected with increasing frequency.

PMID- 24946521
TI  - [Thoracoscopic lobectomy as minimally invasive surgery].
AB  - There has always been a conflict between the proposition that surgical methods
      for treating lung cancer should completely remove the lesion and the seemingly
      contradictory proposition that they should be as minimally invasive as possible.
      The achievement of radicality has been pursued by specializing, and began in 1933
      when Graham performed total pneumonectomy for lung cancer. In 1960, the current
      surgical "gold standard" for lung cancer was reached when anatomical lobectomy
      and lymph node dissection were performed by Cahan, and subsequently called
      "radical lobectomy." The pursuit of less invasiveness began in the early 1980s,
      after the achievement of radicality, and thoracoscopic lobectomy has been
      developed as a major advance. Thoracoscopic lobectomy differs only in the method
      of accessing the pleural cavity: the surgical procedure within the pleural cavity
      does not differ from the procedure for radical lobectomy. In addition, the
      outcome of patients who have undergone thoracoscopic lobectomy as a form of
      minimally invasive surgery has been reported to be better than that after open
      lobectomy, and it is now clear that thoracoscopic lobectomy contributes to
      improving patients' postoperative quality of life. Accumulating additional cases
      and further study will be necessary in the future.

PMID- 24946522
TI  - [Lobectomy for lung cancer using the Da Vinci surgical system].
AB  - Robot-assisted surgery using the da Vinci surgical system has attracted attention
      because of excellent operability without shaking by joint forceps under the clear
      vision of a three-dimensional high-definition camera in lung cancer surgery.
      Although this form of advanced medical care is not yet approved for insurance
      coverage, it is at the stage of clinical research and expected to be useful in
      hilar exposure, lymph node dissection, and suturing of the lung parenchyma or
      bronchus. Lung cancer surgery with the da Vinci system has the advantage of
      combining thoracotomy and minimally invasive surgery in video-assisted thoracic
      surgery. However, safety management, education, and significant cost are problems
      to be resolved. Several important issues such as sharing knowledge and technology
      of robotic surgery, education, training, development of new instruments, and
      acquisition of advanced medical insurance are discussed for the future
      development of robotic surgical systems.

PMID- 24946523
TI  - [The surgical treatment for very low-birth-weight infants].

PMID- 24946524
TI  - [The surgical cure of very low birthweight (including extremely low birthweight)
      infants from the viewpoint of neonatologists (focus on NEC)].

PMID- 24946525
TI  - [What we can learn from a case of medical malpractice-the general manager of team
      based medical care was exempted from liability for breach of the duty of
      explanation even when the said primary physician, entrusted with the
      responsibility of providing preoperative explanation to the patient and his/her
      family, failed to do so-].

PMID- 24946526
TI  - [Tips and pitfalls for adrenalectomy for pheochromocytoma].

PMID- 24946527
TI  - [Clinical practice as a nurse practitioner in surgical wards].

PMID- 24946528
TI  - [Strategies for providing surgery in surrounding local hospitals at regional
      national university hospital].

PMID- 24946530
TI  - [Strategies for elaboration of comprehensive quality standard system on
      traditional Chinese medicine].
AB  - Based on the research goal of "traditional Chinese medicine standards lead in the
      international standard-setting", scientific strategies for the elaboration of
      traditional Chinese medicine (TCM) comprehensive quality standard system were
      introduced. TCM is a complex multi-component system which was used under the
      guidance of traditional Chinese medical theory. The present paper has put forward
      the basic principle of " deep research and simplified standard" to construct the
      quality standards of TCM. " Deep research" refers to systematic, thorough
      investigations on active constituents and biological mechanisms. On the basis of
      deep research, "simplified standard" means to establish a scientific and feasible
      standard, which should be practical and less complicated, to control the quality
      of Chinese herbs. Three key issues related to the elaboration of the quality
      standards are suggested. For reference substances, we propose the research
      methodology using reference extract to develop the qualitative and quantitative
      determination methods. Compared with that of using reference compounds, the
      preparation of reference extract is more accessible, economical and practical.
      Moreover, compared with reference crude drugs, the reference extract showed
      better batch-to-batch consistency. For identification, in addition to
      conventional methods, high performance liquid chromatography (HPLC), chemical
      fingerprints and characteristic chromatogram are proposed, in which more major
      marker compounds are monitored. And then LC-MS technique is employed to
      comprehensively analyze and characterize the peaks in the fingerprint. For multi
      component quantification, the method of single standard to determine multi
      components (SSDMC) is suggested, providing solutions for the lack of reference
      standards in quality evaluation. The SSDMC method uses a single reference
      standard to simultaneously determine the content of multiple compounds. In
      general, the integrate quality control standard of TCM is established based on
      combining innovative technology with practical applications.

PMID- 24946529
TI  - [Pitfalls in informed consent: a statistical analysis of malpractice law suits].
AB  - In medical malpractice law suits, the notion of informed consent is often
      relevant in assessing whether negligence can be attributed to the medical
      practitioner who has caused injury to a patient. Furthermore, it is not rare that
      courts award damages for a lack of appropriate informed consent alone. In this
      study, two results were arrived at from a statistical analysis of medical
      malpractice law suits. One, unexpectedly, was that the severity of a patient's
      illness made no significant difference to whether damages were awarded. The other
      was that cases of typical medical treatment that national medical insurance does
      not cover were involved significantly more often than insured treatment cases. In
      cases where damages were awarded, the courts required more disclosure and written
      documents of information by medical practitioners, especially about complications
      and adverse effects that the patient might suffer.

PMID- 24946531
TI  - [Integrative pharmacology: new paradigm of modernization of Chinese medicine].
AB  - Chinese medicinal formulae( CMF) were often used in the clinics of traditional
      Chinese medicine (TCM) which were critical for modernization of Chinese medicine
      to shed light on the interaction between CMF and biological organisms. In current
      studies, correlation between system and part, macroscopic actions and microcosmic
      mechanism, ADME process and pharmacologic actions were often neglected. Thus, we
      put forward integrative pharmacology, which could integrate the correlation
      between CMF and biological organisms from multi-levels and multi-dimensional
      views. Integrative pharmacology would reveal the molecular mechanism of CMF for
      ailments treatment and screen out effective material systematically, which would
      be the new paradigm of TCM research.

PMID- 24946532
TI  - [Discussion about research progress and ideas on processing mechanism of
      traditional Chinese medicine].
AB  - Study on the processing mechanism of traditional Chinese medicine is the key to
      science of processing Chinese materia medica and modernization of traditional
      Chinese medicine. At present, chemical and pharmacology methods are mainly used
      to discuss the processing principle of efficiency, attenuated, delayed or cooked
      with different treatment. So that the processing mechanism of Chinese herbal
      medicine has made breakthrough progress. With the introduction of modern science
      and technology, biotransformation, intestinal absorption, pharmacokinetics and
      metabolomics methods have been gradually applied in traditional Chinese medicine
      processing mechanism. This article summarizes the achievements in the processing
      mechanism of traditional Chinese medicine in recent years, analyses and discusses
      some main problems, and points out to in-depth study on absorption and
      metabolism, strengthening excipient processing mechanism, paying attention to the
      integration of multiple disciplines and data statistical analysis. Combined with
      years of exploration and practice, the project group proposes a new idea
      "traditional Chinese medicine processing mechanism based on coupled effect of
      chemical composition transformation and intestinal absorption barrier" , which
      provides reference for the study of the mechanism of traditional Chinese medicine
      processing.

PMID- 24946533
TI  - [Construction of research system for processing mechanism of traditional Chinese
      medicine based on chemical composition transformation combined with intestinal
      absorption barrier].
AB  - Based on practice of Epimedium processing mechanism for many years and integrated
      multidisciplinary theory and technology, this paper initially constructs the
      research system for processing mechanism of traditional Chinese medicine based on
      chemical composition transformation combined with intestinal absorption barrier,
      which to form an innovative research mode of the " chemical composition changes
      biological transformation-metabolism in vitro and in vivo-intestinal absorption
      pharmacokinetic combined pharmacodynamic-pharmacodynamic mechanism". Combined
      with specific examples of Epimedium and other Chinese herbal medicine processing
      mechanism, this paper also discusses the academic thoughts, research methods and
      key technologies of this research system, which will be conducive to
      systematically reveal the modem scientific connotation of traditional Chinese
      medicine processing, and enrich the theory of Chinese herbal medicine processing.

PMID- 24946534
TI  - [Discussion on research ideas of synergistic mechanism of Epimedium fried with
      suet oil based on self-assembled micelles formation in vivo].
AB  - Accessories processing is a major feature of traditional pharmaceutical
      technology in China How to use modem science and technology to reveal the
      scientific connotation of accessories processing, is the core of traditional
      Chinese medicine processing research. As traditional beneficial Chinese medicine,
      Epimedium can enhance the effect of warming kidney yang after processing with
      suet oil However, the current literature research from two aspects of chemical
      constituents and pharmacological action cannot fully explain the processing
      mechanism of accessories suet oil. According to the characteristics of fatty
      acids in suet oil with long chain fatty and surface activity, and based on the
      theoretical basis of self-assembled drug delivery system, as well as the
      experimental basis of Epimedium flavonoids self-assembled micelles simulated
      formation and promoting absorption, this paper puts forward the research
      hypothesis on synergistic mechanism of Epimedium fried with suet oil based on
      self-assembled micelles formation in vivo. This paper also describes in detail
      the research ideas and methods of self-assembled micelles enhancing absorption
      and synergistic mechanism of Epimedium flavonoids, which has the important theory
      significance and application value to reveal the scientific connotation of
      Chinese medicine fried with oil.

PMID- 24946535
TI  - [Processing mechanism of Epimedium fried with suet oil based on absorption and
      metabolism of flavonoids].
AB  - As beneficial traditional Chinese medicine, Epimedium fried with suet oil can
      enhance the effect of warming kidney yang. Previous literature studies about
      processing of Epimedium mainly focused on changes in chemical composition and
      pharmacological effect. From the angle of flavonoids absorption and metabolism,
      our group innovatively study the processing mechanism of Epimedium based on
      active component transformation combined with intestinal absorption barrier. The
      processing effect of fried Epimedium can be divided into two key aspects of "
      heat" during processing and processing accessories "suet oil". Through continuous
      three National Natural Science Foundation items, the research group has clarified
      the scientific connotation of "heat" during processing with ADME, and explains
      the synergistic mechanism of processing accessories "suet oil" based on self
      assembled micelles formation in vivo for the first time. This paper summarizes
      the research ideas and results of Epimedium processing mechanism of the project
      team for many years, and discusses the future research direction and content, in
      order to provide new ideas and new methods for modern Chinese medicine processing
      mechanism.

PMID- 24946536
TI  - [Introduction of traditional medicinal plants in Kyrgyzstan].
AB  - Kyrgyzstan is a mountainous country in the northeastern part of Central Asia
      which shares borders to the southeast with China. Due to their extreme
      environment and climate, there are a diverse range of species of plants. Many of
      the plants used in Kyrgyz folk medicine have not been studied using modern
      scientific techniques. This paper introduced the basic situation of medicinal
      herbs in Kyrgyzstan by comparing the differences traditional use between China
      and Kyrgyzstan, and looked for traditional medicinal plant research to provide
      basis for the development and cooperation of China and Kyrgyzstan.

PMID- 24946537
TI  - [MicroRNA and hypertension].
AB  - MicroRNA(miRNA) is involved in virtually all biologic processes, including
      cellular proliferation, apoptosis, and differentiation. Thus, miRNA deregulation
      often results in impaired cellular function and disease development, so miRNAs
      have potential therapeutic relevance. The elucidation of these processes
      regulated by miRNAs and the identification of novel miRNA targets in the
      pathogenesis of hypertension is a highly valuable and exciting strategy that may
      eventually led to the development of novel treatment approaches for hypertension.
      Several mechanisms have been implicated in the pathogenesis of hypertension:
      overactivation of therenin-angiotensin-aldosterone system (RAAS), dysfunction of
      the vascular endothelium, damnification of vascular smooth muscle. To maintain
      and restore target organ expression of miRNA stable may be a new strategy for
      treatment of hypertension. The article reviews pathogenesis of miRNA and
      hypertension, researches of miRNAs as biomarker and therapeutic target, discusses
      advances in miRNA-based approaches that may be important in treating
      hypertension.

PMID- 24946538
TI  - [Advance in studies on long-circulating tumor targeted compound preparations].
AB  - Tumor has long been a hard-nut problem in the world medical field. The effect of
      the conventional drugs is very limited because of the intervention of multiple
      micro-environmental factors during the occurrence and progression of tumors. With
      the characteristics of high efficiency, low toxicity and multi-targets
      synergistic effect, the long-circulating tumor targeted compound preparations
      show its unique advantages in improving tumor microenvironment and enhancing the
      therapeutic effect of treatment, thus it has gradually become a hotspot of
      studies both at home and abroad. Through consulting a great number of
      professional literatures at home and abroad in recent years, the authors
      summarized the current studies in vitro and in vive on long-circulating tumor
      targeted compound preparations in different carriers, in the expectation of
      providing new ideas and methods for the development of long-circulating tumor
      targeted compound preparations.

PMID- 24946539
TI  - [Analysis on signaling pathway network of proliferation of neural stem cells].
AB  - Neural stem cells in brains have capacities of proliferation and differentiation,
      which is very critical to rebuild the cerebral cortex functions. Therefore, it is
      of great importance to find key targets and network pathways that regulate the
      proliferation of neural stem cells, which is also a pressing problem in the
      medical circle. With the Notch pathway as the core of the network, this paper
      summarized the advance of the bimolecular network system composed of Wnt, Shh,
      EGFR, cytokines and Notch signal, and analyzed such key nodes as Notch receptor,
      CBF1, NICD, Hesl, which may become potential targets of new-type drugs in the
      future. With the multi-component, multi-target, multi-lever characteristics,
      traditional Chinese medicines have many common grounds with the network
      pharmacology. The active component groups or active ingredients in traditional
      Chinese medicines are one of the material bases for showing their network
      pharmacological effect, which is worth exploring. This paper aims to provide a
      new strategy for the treatment of neurodegenerative disease and nerve injury with
      traditional Chinese medicines.

PMID- 24946540
TI  - [Advance in saponins of aerial parts of Panax species].
AB  - The bioactivities, chemical composition and distribution of aerial parts of Panax
      species are different from the roots. The present paper summarized the
      phytochemical and analytical studies of aerial parts of Panax species, including
      P. ginseng, P. notoginseng, P. quinquefoliun and P. japonicus. This review aims
      so as to provide scientific evidences for further investigation of chemical
      profile, quality control and optimal utilization of these resources.

PMID- 24946541
TI  - [Preliminary analysis of bitter substances in spica of Prunella vulgaris].
AB  - Volatile oil components and the contents and types of amino acid in spica of
      Prunella vulgaris were analysed by GC-MS and amino acid analyzer. Esters, fatty
      acids, aromatic hydrocarbon, ketone and several alcohol compounds were identified
      by mass spectrum comparison. In these ingredients, beta-ionone smelled aroma of
      cedar, raspberry, nerolidol showed weak sweet soft orange blossom flavor, neroli
      tasted sweet and fresh, nerolidol tasted sweet with light aroma of wood,
      hexadecanal showed a weak aroma of flowers and wax, alpha-sinensal had rich and
      fresh sweet orange flavor. To some extent, these types of aromatic substances can
      affect the taste of herbal tea or decoction made of Spica Prunellae. Among amino
      acids detected, natural amino acids accounted for a larger proportion, and those
      natural amino acids showed bitterness, slight bitterness, sourness (freshness),
      sweetness, slight sweetness, sourness (slight freshness). The results indicated
      that bitter and slightly bitter amino acids have the greatest impacts on the
      sense of Spica Prunellae.

PMID- 24946542
TI  - [Research on spectral reflectance characteristics for Glycyrrhizae Radix].
AB  - In order to study the spectral reflectance differences of Glycyrrhizae Radix
      under different growth conditions and lay the foundation for quantitative
      monitoring of Glycyrrhizae Radix remote sensing images, spectra of Glycyrrhiza
      species under different growth period and different varieties and different
      regions were measured by a portable spectrometer. The results showed that the
      reflectivity of annual G. uralensis was obviously higher than that of the two
      years plant in the visible light band own to the contents of crown layer
      chlorophyll. The reflectivity of two years G. pallidiflora was higher than that
      of G. uralensis in the near infrared band own to the leaf area index and the
      content of leaf water. The red edge spectrum of annual plant fluctuated largely
      than that of two years plant due to vegetation coverage and leaf area index. G.
      pallidiflora grew well than G. uralensis. Under different regions of the
      Glycyrrhiza species, spectral data analysis showed that within a certain range,
      the average annual precipitation and average annual evaporation were the major
      factors to affect the differences of Glycyrrhiza species spectral data under
      different regions owe to the leaf water content, the higher leaf water content,
      the lower spectral reflectance. The principal component analysis and continuum
      removed method of the spectral data under different regions found that, within a
      certain range, the average annual precipitation and average annual evaporation
      were the major factors caused by the differences of Glycyrrhiza species spectral
      data under the different regions, Glycyrrhiza species spectral similarity related
      to the spatial distance.

PMID- 24946543
TI  - [Evaluation of Bupleuri Radix resources in Qingchuan based on DTOPSIS and grey
      related degree].
AB  - In order to select high quality and suitable Bupleuri Radix varieties in
      Qingchuan, and establish a new comprehensive method to evaluation the quality of
      Bupleuri Radix, 12 characters of 14 samples were evaluated by DTOPSIS and grey
      related degree. The results showed that varieties No. 8 and No. 10 had high
      quality. DTOPSIS and grey related degree gave the uniformity result, and the
      biggest difference of value of Ci in DTOPSIS method was 46. 33% , but the biggest
      difference of the weighting correlation number( r (i)) in grey related degree was
      only 13.10%. The DTOPSIS combined with grey related degree can evaluate the
      quality of Bupleuri Radix comprehensively and objectively.

PMID- 24946544
TI  - [Screening and taxonomic identification of endophytic fungi with antitumor and
      antioxidant activities from Artemisia lactiflora].
AB  - Artemisia lactiflora is an important medicinal plant in China. The antitumor and
      antioxidant activities of the extracts of 54 endophytic fungi from the plant were
      screened via MTT assay and DPPH scavenging radical assay, respectively. The
      bioactive strains were identified based on similarity of 5.8S gene and internal
      transcribed spacer (ITS) sequences. The results showed that extracts from ten
      (18.5%) isolates exhibited antitumor activity, and which from two (3.7%) isolates
      exhibited antioxidant activity. The Alternaria sp. GYBH47 strain was
      simultaneously having antagonistic activity against HL-60 leukemia, MCF-7 breast
      and COLO205 colon cell lines, and Phomopsis sp. GYBH42 strain having cytotoxic
      and antioxidant activities. The results indicated that endophytic fungi from
      Artemisia lactiflora are potential resources to find valuable bioactive
      components.

PMID- 24946545
TI  - [Chemical constituents from Pleione bulbocodioides].
AB  - Fourteen compoumds were isolated from the ethyl acetate portion of the 95%
      ethanolic extract of Pleione bulbocodioides by a combination of various
      chromatographic techniques including silica gel, ODS, macroporous adsorbent
      resin, Sephadex LH-20, and preparative HPLC, of which ten compoumds were
      phenanthrenes and dihydrophenanthrenes, two compoumds were bibenzyls, one was
      lignan and a sterol. Their structures were identified on the basis of
      spectroscopic data as monbarbatain A(1), 2, 7, 2'-trihy-droxy-4, 4', 7'
      trimethoxy-1, 1'- biphenanthrene(2), blestriarene A(3), pleionesin B(4), shanciol
      H(5), 17-hydroxy-7'-(4'-hy-droxy-3 '-methoxyphenyl)- 4-methoxy-9, 10, 7', 8'
      tetrahydrophenanthro[2, 3-b]furan-8'-yl methyl acetate(6), 1-p-hydroxybenzyl-4
      methoxy phenanthrene-2, 7-diol(7), 1-p-hydroxybenzyl-4-met-hoxy-9, 10
      dihydrophenanthrene-2, 7-diol(8), hircinol(9), coelonin( 10), gigantol(11),
      batatasin 11 (12), syringaresinol(13) and ergosta4, 6, 8 ( 14) , 22-tetraen-3-one
      (14). Compounds 1-3, 9, 13 and 14 were isolated from this genus for the first
      time.

PMID- 24946546
TI  - [Terpenoids and sterols from Ricinus communis and their activities against
      diabetes].
AB  - Seven terpenoids and three sterols were isolated from the methanol extracts of
      the aerial parts of Ricinus communis by chromatography methods and their
      structures were identified by spectra analysis as ficusic acid( 1), phytol(2),
      callyspinol(3) , lupeol(4), 30-norlupan-3beta-ol-20-one(5) , lup-20(29)-en
      3beta,15alpha-diol(6) , acetylaleuritolic acid( 7), stigmast4-en-3-one(8) , stig
      mast-4-en-6beta-ol-3-one(9) , and stigmast4-en-3,6-dione(10). Compounds 1-3 and 5
      10 were obtained from this species for the first time and 5 and 6 showed
      significant inhibitive activity and good selectivity against 11beta-HSD of mouse
      and human in vitro. [Key words] Ricinus communis; terpenoids; sterols; 11beta-HSD

PMID- 24946547
TI  - [Sesquiterpenoids from Solanum lyratum].
AB  - Ten compounds were isolated and purified by column chromatography over silica
      gel, preparative TLC, and Sephadex LH-20 from the whole plant of Solanum lyratum.
      The structures were elucidated on the basis of physico-chemical properties and
      spectral data as 1beta-hydroxy-1 ,2-dihydro-alpha-santonin (1) , boscialin (2) ,
      blumenol C (3), 3beta-hydroxy-5alpha, 6alpha-epoxy-7-megastigmen-9-one(4),
      dehydrovomifoliol(5) , blumenol A(6), (1'S,2R,5S, 10R) -2-(1', 2'-dihydroxy-l1'
      methylethyl) -6,10-dimethylspiro[4,5] dec-6-en-8-one(7) , (1'R,2R,5S,10R)-2-(
      1',2'-dihydroxy-l '-methylethyl) -6,1 l0-dimethylspiro[4,5]dec-6-en-8-one( 8) , 2
      (1',2'-dihydroxy-1 '-methylethyl) -6,1 0-dimethyl-9-hydroxyspiro [4,5] dec-6-en-8
      one (9) , and grasshopper ketone (10). Compounds 1-10 were isolated from this
      plant for the first time.

PMID- 24946548
TI  - [Identification of constituents in Suanzaoren tang by LC-Q-TOF-MS and LC-IT-MS].
AB  - LC-Q-TOF-MS and LC-IT-MS in positive and negative ion mode were applied to
      simultaneously characterize the constituents in Suanzaoren tang. Analysis was
      performed on an Agilent Zorbax SB-C18, Rapid Resolution HT column(4.6 mmx 50 mm,
      1. 8 micro m) with gradient elution of acetonitrile(A) -aqueous solution
      containing 0. 05% formic acid(B) at a flow rate of 0. 6 mL min(-1) and the column
      temperature was 30 degreesC. By comparing MS fragmentation, accurate molecular
      weight, literature date and standard compounds information, a total of48
      compounds were successfully identified or speculated. The origins of these
      compounds were assigned to the corresponding Chinese medicine. Thirty-one
      compounds were reported in Suanzaoren tang for the first time. LC-Q-TOF-MS
      combined with LC-IT-MS is a simple and rapid tool for the identification of
      constituents of Suanzaoren tang, and the results could provide evidence for the
      research on quality combined and effective constituents of Suanzaoren tang.

PMID- 24946549
TI  - [Study on distribution and dynamic accumulation of catalpol and total iridoid in
      fresh Rehmannia glutinosa].
AB  - Iridoid glycosides were the main active ingredient of Rehmannia glutinosa, of
      which catalpol has the highest content. This work will provide theoretical basis
      for metabolic study and cultivation of iridoids on the basis of the dynamic
      accumulation of catalpol and total iridoids in the growth of R. glutinosa. The
      samples of rehmannia 85-5 were gathered in the same filed from July to October.
      The contents of catalpol and total iridoid glycosides were measured by HPLC and
      specteophotometric, respectively. The results showed that youngest leaves had the
      higher content of catalpol and total iridoid glyosides than that of the other two
      leaf ages in the same growth stage from July to September, while their content of
      catalpol and total iridoid glycosides were all decreased as the growth of leaves
      of R. glutinosa. The content of catalpol didn't differ significantly from July to
      September, whereas it has significantly increased in October in the three leaf
      stage. In the same stage, the wider the root diameter is, the higher content of
      the effective components are. In August and September, the total iridoid
      glycosides have the fastest accumulation. The content of catalpol was increased
      as the accumulation of total iridoid glycosides.

PMID- 24946550
TI  - [Protective effect of oxymatrine on chronic heart failure and ADMA metabolism
      pathway in isoproterenol-induced chronic heart failure in rats].
AB  - OBJECTIVE: To investigate the protective effects of oxymatrine on chronic heart
      failure induced by isoproterenol (ISO) and to observe its effects on ADMA
      metabolism pathway in ISO-induced chronic heart failure in rats. METHOD: Male
      Sprague-Dawley rats were given oxymatrine (100,50 mg kg-1) orally for 14 days.
      Heart failure was induced in rats by subcutaneous injection of isoproterenol (5
      mg kg-1 d-1 ) at the 8th day for 1 week. Serum parameters, haemodynamic
      parameters, Heart weight, and histopathological variables were analysed.
      Expression of protein levels were measured by Western blot. RESULT: Oxymatrine
      (100,50 mg kg-1) significantly attenuated serum content of cTn I, improved left
      ventricle systolic and diastolic function and left ventricular remodeling,
      reduced the ISO-induced myocardial pathological changes compared with ISO group.
      In addition, oxymatrine (100,50 mg kg-1) significantly reduced serum level of
      ADMA (P <0. 01), normalize the reduced dimethylarginine dimethylaminohydrolase 2
      (DDAH2) expression (P <0. 01) , but had no effect on the isoproterenol-induced
      upregulated protein arginine methyltransferases 1 expression. CONCLUSION:
      Oxymatrine could ameliorate the experimental ventricular remodeling in ISO
      induced chronic heart failure in rats and the mechanism involved in reducing
      serum content of ADMA and increased DDAH2 expression.

PMID- 24946551
TI  - [Effect of Moutan Cortex on AGEs-induced mesangial cell proliferation and
      basement membrane thickening].
AB  - OBJECTIVE: To investigate the effect of Moutan Cortex on mesangial proliferation
      and basement membrane thickening induced by advanced glycation end products
      (AGEs). METHOD: The glomerular mesangial cells (MC) injury model was established
      by inducing by AGEs. The cell were divided into 6 groups: the blank group ( BSA,
      200 mg L-1) , the model group (AGEs, 200 mg L-1), the positive control group (AG,
      10 mmol L L-1), and drug administration groups, namely the Moutan Cortex-treated
      high-dose group (2 x 10(-4) g mL(- 1)), the Moutan Cortex-treated medium-dose
      group (1 x 10(-4) g mL-1 ), and the Moutan Cortex-treated low-dose group (0. 5 x
      10(-4) g . mL(-1)). The MTT method was performed to observe the effect of Moutan
      Cortex on the proliferation of MC. The content of fibronectin (FN) and collagen
      secretion 1V (Col IV) in cell supernatant were detected by ELISA kits. The
      western blot analysis was carried out to observe the FN expression. The Real-time
      PCR analysis was applied to examine the Col IV mRNA expression. RESULT: AGEs
      significantly increased AGEs-induced MC proliferation and FN and Col 1V
      secretion. The western blot analysis showed that MC could down-regulate the FN
      expression of MC secretion. According to the results of the real-time PCR assay,
      MC could down-regulate AGEs-induced MC secretion Col IV mRNA expression.
      CONCLUSION: MC had a certain protective effect on MC cultured under AGEs
      conditions. MC could remarkably inhibit the composition and secretion of Col IV
      and FN in matrix and the basement membrane thickening, and provide an
      experimental basis for the treatment of diabetic nephropathy.

PMID- 24946552
TI  - [Effect of formula of removing both phlegm and blood stasis in improving cardiac
      function of Chinese mini-swine with coronary heart disease of phlegm-stasis
      cementation syndrome].
AB  - OBJECTIVE: To evaluate that the effect of formula of removing both phlegm and
      blood stasis in improving cardiac function of Chinese mini-swine with coronary
      heart disease of phlegm-stasis cementation syndrome. METHOD: Totally 36 Chinese
      mini-swine were randomly divided to six groups: the normal control group, the
      model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with
      doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the
      normal control group, all of other groups were fed with high-fat diet for 2
      weeks. Interventional balloons are adopted to injure their left anterior
      descending artery endothelium. After the operation, they were fed with high-fat
      diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis
      cementation syndrome. After the operation, they were administered with drugs for
      8 weeks. The changes in the myocardial ischemia were observed. The changes in the
      cardiac function and structure were detected by cardiac ultrasound and
      noninvasive hemodynamic method. RESULT: Compared with the normal control group,
      the model group showed significant increase in myocardial ischemia and SVR and
      obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05
      or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs,
      EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the
      model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac
      function, and improve the abnormal cardiac structure and function induced by
      ischemia (P <0. 05 or P <0. 01). CONCLUSION: TYTZ shows a significant effect in
      improving cardiac function of Chinese mini-swine with coronary heart disease of
      phlegm-stasis cementation syndrome. The clinical cardiac function detection
      method could be adopted to correctly evaluate the changes in the post-myocardial
      ischemia cardiac function, and narrow the gap between clinical application and
      basic experimental studies.

PMID- 24946553
TI  - [Effect of synchronous perfusion of NaN3 in changes in content of cholinergic
      neurotransmitter in medial prefrontal cortex and hippocampal extra-cellular
      fluid].
AB  - OBJECTIVE: To observe the effect of synchronous perfusion of specific respiratory
      chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial
      prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in
      hippocampal extra-cellular fluid, and establish the AD rat model induced by
      mitochondrial acute injury. METHOD: The synchronous dual-probe dual-channel brain
      microdialysis sampling technology was applied to synchronously perfuse modified
      Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol
      L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and
      continuously collect dialysates from different encephalic areas. Dynamic contents
      of ACh and Ch were determined by high performance liquid chromatography-post
      column immobilized enzyme reactor-electrochemical process. RESULT: ACh and Ch
      contents in mPFC extracellular fluid of normal rats were higher than that in
      hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh
      in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and
      constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus.
      CONCLUSION: The synchronous perfusion of NaN3in rat mPFC and hippocampus can
      injure functions of the cholinergic nerve projection area, and cause the acute AD
      model with ACh and Ch metabolic disorders. This model can be used in pathogenetic
      and pharmacological studies.

PMID- 24946554
TI  - [Comparative study on effects of Rubiae Radix et Rhizoma and carbonized Rubiae
      Radix et Rhizoma on acute blood stasis rat model].
AB  - OBJECTIVE: To observe the effects of Rubiae Radix et Rhizoma (RRR) and carbonized
      Rubiae Radix et Rhizoma (CRRR) on the acute blood stasis rat model, and reveal
      their differences in efficacy. METHOD: The acute blood stasis model was induced
      by subcutaneously injecting adrenaline hydrochloride and soaking in ice water.
      Yunnan Baiyao was used as the positive control drug, and administered for
      consecutively seven days. This model was adopted to observe the effect of high,
      middle and low dose RRR and CRRR groups on hemorheology, thrombin activity, and
      blood platelet system. RESULT: RRR could significantly reduce the wholeblood
      viscosity and plasma viscosity of blood stasis rats under different shear rates,
      and showed certain two-way regulating function in hemostasis. It also showed
      certain effect on ADP-induced platelet aggregation rate, but which was lower than
      CRRR. CRRR achieved the main hemostatic mechanism by stimulating intrinsic and
      extrinsic blood coagulation and fibrinogen, and could significantly enhance the
      platelet aggregation rate of rats in the acute blood stasis model (P <0. 01).
      CONCLUSION: RRR had the effect of removing blood stasis and hemostasis, while
      CRRR mainly has the hemostatic effect. This further demonstrates the traditional
      processing theory of "promoting blood circulation with crude herbs and stopping
      bleeding with processed herbs".

PMID- 24946555
TI  - [Study on drug properties of components in Euodiae Fructus based on rat stress
      gastric ulcer model with cold syndrome].
AB  - OBJECTIVE: To clarify drug properties of components in Euodiae Fructus. METHOD:
      The rat cold syndrome model was induced by cold water stress method. The content
      of neurotransmitters sand hormones such as DA, 5-HT, NE, AChE and 17-OHCS in
      serum of model rats were taken as the indexes to evaluate drug properties of
      components in Euodiae Fructus. RESULT: Euodiae Fructus and its components could
      correct or relief the content of energy metabolism and substance metabolism
      related neurotransmitters sand hormones in serum of model rats with water
      stressed cold syndrome. CONCLUSION: Euodiae Fructus and its components are proved
      to show hot property.

PMID- 24946556
TI  - [Protective effect of Shenxiong injection on cerebral ischemia-reperfusion injury
      of rats].
AB  - OBJECTIVE: To study the protective effect of Shenxiong injection on the cerebral
      ischemia-reperfusion injury of senile rats. METHOD: Totally 108 Sprague-Dawley
      (SD) rats were randomly divided into the sham operation group, the model group,
      the Ni-modipine group and Shenxiong injection groups (low, middle, and high
      doses). The rat brain ischemia-reperfusion model was established by the middle
      cerebral artery occlusion (MCAO) method in rats, in order to observe the effect
      of Shenxiong injection on neurological score and brain infarct volume of rats
      with cerebral ischemia-reperfusion injury, and determine the contents of NOS, NO,
      SOD, MDA and LDH in brain tissues. The contents of TNF-alpha and IL-1beta levels
      in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA)
      method. RESULT: Shenxiong injection could significantly decrease neurological
      score, injury degree of brain tissues and brain infarct volume of rats with
      cerebral ischemia-reperfusion injury, increase the vigor of SOD, decrease the
      levels of MDA, NO, NOS and LDH, and inhibit IL-1beta and TNF-alpha expressions.
      CONCLUSION: Shenxiong injection has the obvious protective effect on the brain
      ischemia-reperfusion injury in rats. Its mechanism may be related to the
      improvement of neurological function, the reduction of free radical injury, and
      the inhibition of inflammation factor expression.

PMID- 24946557
TI  - [Effect of curcumin on radiosensitization of CNE-2 cells and its mechanism].
AB  - OBJECTIVE: To investigate the effect of curcumin (Cur) on radiosensitivity of
      nasopharyngeal carcinoma cell CNE-2 and its mechanism. METHOD: The effect of
      curcumin on radiosensitivity was determined by the clone formation assay. The
      cell survival curve was fitted by Graph prism 6. 0. The changes in cell cycle
      were analyzed by flow cytometry (FCM). The differential expression of long non
      coding RNA was detected by gene chip technology. Part of differentially expressed
      genes was verified by Real-time PCR. RESULT: After 10 micro mol L-1 Cur had
      worked for 24 h, its sensitization enhancement ratio was 1. 03, indicating that
      low concentration of curcumin could increase the radiosensitivity of
      nasopharyngeal carcinoma cells; FCM displayed a significant increase of G2 phase
      cells and significant decrease of S phase cells in the Cur combined radiation
      group. In the Cur group, the GUCY2GP, H2BFXP, LINC00623 IncRNA were significantly
      up-regulated and ZRANB2-AS2 LOC100506835, FLJ36000 IncRNA were significantly down
      regulated. CONCLUSION: Cur has radiosensitizing effect on human nasopharyngeal
      carcinoma CNE-2 cells. Its mechanism may be related to the changes in the cell
      cycle distribution and the expression of long non-coding IncRNA.

PMID- 24946558
TI  - [Experimental study on pseudoallergic reaction of Qingkailing injection].
AB  - Pseudoallergic reactions of Qingkailing injection (QKLI) was assessed by vascular
      hyperpermeability which were indicated by ear blue staining in ICR mice after
      single intravenous injection of QKLI mixed with Evans blue (EB) and skin blue
      spot formation in SD rats after intradermal injection of QKLI and intravenous
      injection of EB. In addition, QKLI-induced histamine, VEGF, TNF-alpha release was
      measured after ICR mice received the single dosing of QKLI iv. The mild vascular
      hyperpermeability characterized by ear blue staining could be observed in mice
      after intravenous injection of QKLI and EB. Intracutaneous injection of 50 micro
      L of test solution containing QKLI (25,50 microL) in rat back skin caused obvious
      local vascular hyperpermeability at the injection sites so as to result the
      larger diameters of blue spots than that in negative control group (P <0. 01).
      QKLI induced a significant increase of VEGF and a slight elevation of histamine
      in mice after intravenous administration, while TNF-alpha showed no change after
      QKLI iv. The results in this study indicated that both intravenous injection and
      intracutanous injection of QKLI could induce vascular hyperpemeability so as to
      cause pseudoallergic reaction in mice and rats. QKLI-induced pseudoallergic
      reaction may be associated with the release of histamine and VEGF.

PMID- 24946559
TI  - [Establishment of Caco-2 cell monolayer model with collagen coating 6-well plates
      for study of traditional Chinese medicine prescription].
AB  - Caco-2 cell monolayer model is widely utilized in drug absorption study and 12
      well transwellTM plates were commonly used to study the absorption of different
      kinds of natural products. To establish a stable method for the study of
      traditional Chinese medicine prescription, 6-well plates were chosen because of
      the larger well volumes than 12-well plates. To study the impacts of collagen
      kinds, coating density as well as coating time on the cell culture, the
      transepithelial electrical resistance of Caco-2 cell monolayers grown on
      different collagen coating transwells was determined, and the permeations of
      propranolol and atenolol as standard markers were detected with HPLC. The results
      showed that the kinds of collagen, the different coating densities and coating
      time of rat tail collagen had no significant influences on the Caco-2 cell
      monolayer integrality and absorption capacity. 6-well plates coated with 2 micro
      g Scm-2 rat tail collagen for 1 hour were enough reliable and suitable for the
      study of traditional Chinese medicine prescription in vitro.

PMID- 24946560
TI  - [Total quantity statistical moment analysis on pharmacokinetics of rhein and
      chrysophanol after oral administration of Quyu Qingre granules in normal and
      acute blood stasis rabbits].
AB  - This study aim to reveal the total pharmacokinetics of rhein and chrysophanol
      after oral administration of Quyu Qingre granules (QUQRG) in normal and acute
      blood stasis rabbits, to identify the pharmacokinetics differences between two
      groups of rabbits and to evaluate the applicability of the total statistical
      moment analysis. Based on the concentrations of rhein and chrysophanol in plasma
      determined by an established HPLC method, and the calculation of main total
      pharmacokinetic parameters, this study found that total pharmacokinetic
      parameters VRT, value of blood stasis group is lager than that of normal group
      and the difference is significant Compared with normal group, total
      pharmacokinetic parameters AUC,, MRT,, t1/2t, and Vt value of blood stasis group
      is lager, while the k, and CL, value is smaller. The findings indicated that the
      absorbed and released time of rhein and chrysophanol was accelerated and the
      total absorptive amount of these two compounds was increased in rabbits with
      acute blood stasis, compared with the normal rabbits. Total quantity statistical
      moment analysis can combine the pharmacokinetics of rhein and chrysophanol and
      express the pharmacokinetic behavior of these two compounds in QUQRG. The
      parameters in this paper can provide reference frames for the follow-up
      development of QUQRG.

PMID- 24946561
TI  - [Study on mechanism of combined administration of Coptidis Rhizoma and Rehmanniae
      Radix in treating type II diabetes mellitus].
AB  - To make a preliminary study on the mechanism of Coptidis Rhizoma(CR) and
      Rehmanniae Radix(RR) before and after the combined administration in treating
      type II diabetes mellitus. The type I diabetes animal model in rats was
      established by fat emulsion and intraperitoneal injection with streptozotocin, in
      order to compare the hpyerglycemic and hypolipidemic effects of CR, RR and their
      combined administration of different ratio. The urinary metabolic profiling in
      rats of Coptidis Rhizoma and Rehmanniae Radix before and after the combined
      administration was analyzed by using the gas chromatography-mass spectrometry.
      The differences among groups in metabolome were analyzed by the principal
      component analysis (PCA). The biochemical index results indicated that both CR
      and RR before and after the combined administration could lower high blood
      glucose, hypertriglyceride and high cholesterol. According to the analytical
      results of PCA of the rats' urine samples, the CR group was the most close to the
      normal group, with no significant difference in CR and RR group of different
      combination ratios. Twelve differentiated metabolites were identified to be
      related to type II diabetes. Compared with the normal group, the CR-treated group
      showed significant increase in seven differentiated metabolites. Among CR and RR
      drugs with different combination ratios, CR played a major role and thus acted as
      the monarch drug. Whereas RR served as the ministerial drug and assisted CR to
      show the efficacy. This study laid a foundation for the explanation of the
      combination mechanism of traditional Chinese medicines.

PMID- 24946562
TI  - [Randomized, double-blind, multi-center, positive parallel control clinical trial
      of compound Wuzhigan capsules on anemopyretic cold].
AB  - Compound Wuzhigan capsules is a compound preparation composed of Wuzhigan,
      Shidagonglao, Gangmei, Shanzhima. A Randomized, double-blind, multi-center,
      positive parallel control designed to evaluate the clinical efficacy and safety
      of compound Wuzhigan capsules on anemopyretic cold. One hundred and twenty
      anemopyretic cold patients were given compound Wuzhigan capsules (test group), 2
      capsules one time, three times a day, 119 patients were given compound Wuzhigan
      tablets (control group) ,4 tablets one time, three times a day; three days of
      treatment The study showed, the markedly effective rate and total effective rate
      respectively were 63. 3% and 80% of the test group. For the control group, the
      markedly effective rate and total effective rate respectively were 72. 5% and 80.
      7%. The difference was not statistically significant. Compound Wuzhigan capsules
      can reduce the dosage, and get better patient compliance.

PMID- 24946564
TI  - [Clinical observation of traumatic ankle arthritis with orthopedics lotion on 60
      cases].
AB  - Observing the clinical curative effect of orthopedics lotion to treat traumatic
      ankle arthritis, the outpatient department of orthopedics in Guang'anmen Hospital
      collected 60 cases who were diagnosed as traumatic ankle arthritis. The cases who
      already met the inclusion criteria, were randomly divided into the treatment
      group (30 cases) and control group (30 cases). Thirty patients in treatment group
      were received fumigation treatment with orthopedics lotion; 30 patients in
      control group were treated by intra-articular injection of sodium hyaluronate.
      After 5 weeks treatment, the effects on the both groups would be observed and
      analysed. Baird-Jackson scoring system was used to assess the overall curative
      effect. Visual analogue scales (VAS) was used to assess analgesic effect. BJ
      scores of pre-treatment and post-treatment in both the treatment group and the
      control group were compared, P <0O. 01, significantly different; and the BJ
      scores after treatment of two groups were compared by paired t-test, the t value
      is 1. 76, there was no significant difference between two groups. Both of the
      treatments were effective, but there was no significant difference in overall
      curative effect between the two kinds of treatment. The VAS scores after
      treatment of two groups were compared by paired t-test, the t value was 2. 282,
      and there was a significant difference between two groups (P <0. 05). The
      analgesic effect shown in treatment group was better than the control group. The
      results suggest that: orthopedics lotion is a effective way to treat traumatic
      ankle arthritis, and it has significant effect on analgesic.

PMID- 24946563
TI  - [Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/
      prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis].
AB  - Triptolide (TPT), an active compound extracted from Chinese herb Tripterygium
      wilfordii , has been used in therapy of rheumatoid arthritis (RA). In this study,
      after synovial fibroblasts from rheumatoid arthritis (RASFs) were treated with
      TPT, we investigated its effect on the differentiation of Th17 cells. Firstly,
      the mRNA level of cyclooxygenase (COX) wad detected by qRT-PCR and the protein
      level of prostaglandin E2 (PGE2) was tested by ELISA in RASFs treated with
      different concentrations (0, 10, 50, 100 nmol L-1 ) of TPT. Then after TPT pre
      treated RASFs and RA CD4 + T cells wer e co-cultured for 3 days in the presence
      or absence of PGE2, IL-17 and IFN-gamma production in CD4 T cell subsets were
      detected by flow cytometry. The results showed TPT decreased the mRNA experssion
      of COX2 and the secretion of PGE2 in RASFs in a dose-dependent manner(P <0. 05).
      We further found that differentiation of Thl7 cells was downregulated in a dose
      dependent manner, and exogenous PGE2 could reverse the inhibition of Th17 cell
      differentiation(P <0. 05). Taken together, our results demonstrated that TPT
      inhibited the mRNA level of COX2 and the secretion of PGE2 in RASFs, which partly
      led to impaired Th17 cell differentiation in vitro.

PMID- 24946565
TI  - [Peripheral blood cell factors of Graves ophthalmopathy and effect of
      intervention with tripterygium glycosides].
AB  - To explore the effect of tripterygium glycosides on the level of peripheral blood
      cell factors of Graves ophthalmopathy (GO). In the study, 64 patients of GO in
      moderate-severe acute stage were selected, and randomly divided into the
      treatment group (32 cases) and the control group (32 cases). Both of the two
      groups were provided with basic treatment. The control group was added with
      prednisone(0. 75 mg kg-1 d-1 ), which gradually reduced (by 5-10 mg week-1 )to
      the minimum dose of 5 mg d-1. The treatment group was treated with 20 mg
      tripterygium glycosides, three times a day. One therapy course is three months.
      The levels of peripheral blood cells(TNF-alpha , IL-2, IL-10, IFN-gamma)of the
      two groups before and after the treatment and the clinical efficacy were
      observed. The study indicated that, before the treatment, TNF-alpha, IL-2, IFN
      gamma in both groups were significantly higher than that in the health group, but
      with IL-10 notably lower than the healthy group. After the treatment, TNF-a, IL
      2, IFN-gamma in the treatment group significantly decreased, but with IL-10
      significantly increasing (P <0. 01). After the treatment, the two groups showed
      significant difference (P <0. 01). The total clinical efficacy in the treatment
      group was 88. 10% , and that in the control group was 57. 14% (P <0. 01). After
      the treatment, the two groups showed significant changes in the exophthalmos
      degree (P < 0. 01). The results showed that the level of peripheral blood cells
      (TNF-alpha,IL-2, IL-10, IFN-gamma)of GO patients was positively correlated with
      the severity of ocular disease. The combined therapy of tripterygium glycosides
      and methimazole show such advantages as low side effect and high clin-

PMID- 24946566
TI  - [Study on determination of Chinese medicine flavor and its regularity].
AB  - Five flavors are basic nature of Chinese medicine. But the labeling of Chinese
      medicine flavors was in a chaos. Song Jin and Yuan dynasty is a transconformation
      stage of labeling Chinese medicine flavors. In this article the author put
      forward that the determination of Chinese medicine flavor shifted from tasting of
      early and middle age of Northern Song dynasty to categorical analogizing and
      functional analogizing in the late age of Northern Song dynasty. The latter
      method had a flourished development in Southern Song, Jin and Yuan dynasty. This
      regularity conclusion has provided a reference for the standardizing Chinese
      medicine flavors.

PMID- 24946567
TI  - [Analysis of characteristics of black carbon concentration in Shanghai from 2008
      to 2012].
AB  - The variations of black carbon (BC) mass concentration in Shanghai are analyzed
      and discussed by using hourly averaged data monitored continuously at Shanghai
      Urban Environmental Meteorological Center from January 2008 to December 2012. The
      results show that the annual mean mass concentration of BC decreased from (4
      045.3 +/- 3 375.4) ng x m(-3) in 2008 to (2 766.2 +/- 2 078.9) ng x m(-3) in
      2012, and the annual changes are 2.3%, - 6.5%, -18.7% and -12.1%, respectively.
      The yearly averaged BC mass concentration in Shanghai is on the low side of
      middle-level compared with other mega-cities of China. According to the test
      data,the highest monthly averaged concentration of BC appeared in November and
      December,which were 5 426.6 ng x m(-3) and 5 365.3 ng x m(-3), respectively,and
      then in January, June and October, which were 4402.5, 3763.3 and 3412.7 ng x m(
      3), respectively. The diurnal cycles of the BC mass concentration show that there
      are two obvious peaks during morning 07:00-10:00 and during evening 18:00-22:00
      Beijing time (BT), and the first peak was higher than the second on weekdays, but
      opposite on weekends and holidays. The daily mean mass concentration of BC was 9%
      higher on weekdays than on weekends and holidays. In addition, an empirical
      equation is obtained for daily BC concentration estimation and prediction using
      all the effective test data during the 5-year observation period and employing
      the regression analysis.

PMID- 24946568
TI  - [Chemical characteristics and insoluble particulates' surface morphology of a
      snowfall process in the southeastern suburb of Urumqi].
AB  - In order to understand the composition and potential pollution of metal elements
      in precipitation in the southeastern suburb of Urumqi on February 21 to 23, 2012,
      soluble elements were determined by inductively coupled plasma mass spectrometry
      (ICP-MS); in addition, energy spectrum and morphological analysis were made for
      insoluble particulates. The results showed that the content of toxic heavy metals
      in snowfall was a little high; and the enrichment factors of Se, As and Cd were
      124.65, 57.69 and 36.70, respectively, showing a typical coal pollution
      characteristic. The back trajectory cluster analysis suggested that the coal fly
      ash of snowfall mainly induced by air masses originated from the coal-fire power
      plant in the Southwestern sampling site. Morphology analyses conducted under an
      scan electron microscope demonstrated fly ash coming from coal burning process
      and irregular mineral are in the majority of insoluble particulates in snowfall,
      soot aggregates were compact, when the soot was wetted (the hygroscopic
      behaviour), and the morphology changed further. Insoluble particulates of the
      southeastern suburb of Urumqi were coal fly ash and insoluble soil minerals.

PMID- 24946569
TI  - [Comparative study of the level and distribution of polybrominated diphenyl
      ethers and new brominated flame retardants in the atmosphere of typical urban].
AB  - Brominated flame retardants (BFRs) are widely used in industrial and commercial
      products and are frequently detected in various environmental media. It might be
      potential harm to the environment and the human body. This study reported the
      levels of 8 kinds of polybrominated diphenyl ethers (PBDEs: BDE-28, -47, -100, 
      99, -154, -153, -183, -209) and 3 kinds of new brominated flame retardants
      (NBFRs: PBT, PBEB, HBB) in the atmosphere of Binhai Development Zone, Weifang
      City, Shandong Province, which was taken as a BFR production source area and of
      Nanning City, Guangxi Province, which was taken as a contrast area. The results
      showed that the average concentrations of sigma8 PBDEs in the atmosphere of
      Weifang and Nanning were 1.4 x 10(5) pg x m(-3) and 323.0 pg x m(-3),
      respectively, and the average concentrations of sigma3 NBFRs were 4.2 x 10(3) pg
      x m(-3) and 11.9 pg x m(-3), respectively. Compared with other cities, the
      concentrations of BFRs in the atmosphere of the production area were at a high
      level in the globe, and the concentrations of BFRs in Nanning were similar with
      other cities in China. The distribution characteristics of PBDEs and NBFRs in the
      atmosphere of the production area were different from those of Nanning, and the
      correlations between PBEB, PBT, HBB and BDE-209 were different between Weifang
      and Nanning.

PMID- 24946570
TI  - [Source and health risk assessment of heavy metals in ambient air PM10 from one
      coking plant].
AB  - To investigate the sources and health risk of heavy metals in ambient air PM10
      from the coking plant, the PM10 in the air around one coking plant was collected
      in June 2012. Then the heavy metals concentrations in PM10 were tested by the
      microwave-ICP-MS method. Furthermore, the USEPA's human exposure assessment model
      was applied to preliminarily evaluate the human health risks of the heavy metals
      in air particulate matter. The results show that the concentrations of 10 kinds
      of heavy metals in PM10 from the coking plant vary significantly, ranging from
      3.06 x 10(-5) mg x m(-3) to 1.77 x 10(-2) mg x m(-3), of which the concentration
      of Cr is the highest, while the concentration of Co is the lowest, and the
      concentration of the carcinogenic substances is higher than that of the non
      carcinogenic substances. The coking plant is identified to be the major source of
      the heavy metals in ambient air PM10, and Ni is the main polluting heavy metal.
      Moreover, the heavy risk assessment results reveal that the carcinogenic risks
      for adults are higher than children, while the carcinogenic risks in industrial
      areas and school relatively large. The non-carcinogenic risks for children are
      the highest in all the population, and the non-carcinogenic risks in residential
      area can not be ignored. Among the carcinogenic substances, the potential
      carcinogenic risks of Cd, Cr and As are comparatively large, Ni and Co have
      certain potential risks. Whereas, among the non-carcinogenic substances, the non
      carcinogenic risks of Mn is great. Consequently, relevant departments should pay
      close attention to this situation.

PMID- 24946571
TI  - [Estimation of average traffic emission factor based on synchronized incremental
      traffic flow and air pollutant concentration].
AB  - On-road vehicle emissions have become the main source of urban air pollution and
      attracted broad attentions. Vehicle emission factor is a basic parameter to
      reflect the status of vehicle emissions, but the measured emission factor is
      difficult to obtain, and the simulated emission factor is not localized in China.
      Based on the synchronized increments of traffic flow and concentration of air
      pollutants in the morning rush hour period, while meteorological condition and
      background air pollution concentration retain relatively stable, the relationship
      between the increase of traffic and the increase of air pollution concentration
      close to a road is established. Infinite line source Gaussian dispersion model
      was transformed for the inversion of average vehicle emission factors. A case
      study was conducted on a main road in Beijing. Traffic flow, meteorological data
      and carbon monoxide (CO) concentration were collected to estimate average vehicle
      emission factors of CO. The results were compared with simulated emission factors
      of COPERT4 model. Results showed that the average emission factors estimated by
      the proposed approach and COPERT4 in August were 2.0 g x km(-1) and 1.2 g x km(
      1), respectively, and in December were 5.5 g x km(-1) and 5.2 g x km(-1),
      respectively. The emission factors from the proposed approach and COPERT4 showed
      close values and similar seasonal trends. The proposed method for average
      emission factor estimation eliminates the disturbance of background
      concentrations and potentially provides real-time access to vehicle fleet
      emission factors.

PMID- 24946572
TI  - [Study on critical loads of sulfur and nitrogen in the Pearl River Delta].
AB  - Supported by the geographical information system (ArcGIS), critical loads and
      exceedances of critical loads of sulfur and nitrogen in the Pearl River Delta
      (PRD) were calculated using Steady-state Mass Balance method with current
      deposition data, vegetation data and soil data obtained by field sampling and
      laboratory analysis. Results showed that the present critical loads of sulfur
      were high in the eastern PRD and low in the west. Higher critical loads occurred
      in most of Huizhou, north-central Guangzhou, Dongguan and south Zhongshan. The
      critical loads of these regions were mostly larger than 15 keq x (hm2 x a)(-1).
      Regions with lower critical loads included most of Jiangmen, most of Zhaoqing and
      part of Shenzhen with critical loads less than 2 keq x (hm2 x a)(-1). Critical
      loads of nitrogen were mainly in the range of 1.0-2.5 keq x (hm2 x a)(-1) while
      values lower than 1.0 keq x (hm2 x a)(-1) were found in Zhaoqing. According to
      the results of critical load exceedances, in several regions the sulfur
      deposition exceeded the critical loads whereas in most regions the nitrogen
      deposition exceeded the critical loads. With the reduction of particulate
      concentrations in atmosphere in the future, critical loads of sulfur would
      decrease and sulfur depositions in most regions would exceed their critical
      loads. Therefore, the control over nitrogen deposition should be strengthened in
      the present situation and special attention should be paid to the control of
      sulfur deposition with the reduction of particulate concentrations in the future.

PMID- 24946573
TI  - [Hydrogen sulfide removal by the combination of non-thermal plasma and biological
      process].
AB  - A bench scale system integrating a non-thermal plasma (NTP) unit with a
      biotricking filtration (BTF) unit for the treatment of gases containing hydrogen
      sulfide (H2S) was investigated. The additional use of the biotrickling filter to
      NTP reactor not only leads to the enhancement of hydrogen sulfide removal
      efficiency up from 83.4% to 90.1%, but also eliminates gas-phase intermediate
      products from NTP degradation of H2S to produce sulfate and H2O. The dynamic
      changes of microbial community in BTF influenced by ozone from NTP were assessed
      by PCR-DGGE. Results show that the microbial community was affected by ozone.
      After the integration, a part of microorganisms disappeared, and meanwhile some
      new microorganisms appeared. The microbial community structure in BTF changed
      from eight bands to nine bands; three bands which have the functions of
      desulfurization disappeared and four bands which have the functions of
      desulfurization appeared; five bands which have the functions of desulfurization
      and sulfate reduction were unchanged. The bacterial groups in the BTF unit of NTP
      BTF system include Uncultured Thiobacillus sp., Acidithiobacillus thiooxidans
      strain dfI, Uncultured Thiobacillus sp., Uncultured Acidiphilium sp., Uncultured
      Xanthomonadaceae bacterium clone SBLE6C12, Uncultured 8-Proteobacterium and
      Paracraurococcus sp. 1PNM-27.

PMID- 24946574
TI  - [Spatial distribution and risk assessment of atrazine in Taizi River basin,
      China].
AB  - Atrazine (AT) has been detected in surface water and groundwater in many
      countries and regions around the world. Concentrations of AT in surface water,
      suspended particulate matter (SPM) and groundwater samples collected from the
      Taizi River basin, in northeast China, were analyzed using a gas chromatograph
      mass spectrometer (GC-MS) in order to clarify their spatial distribution and
      environmental behavior, and to assess their potential ecological risk.
      Concentrations of AT varied from 0-734.0 ng x L(-1) for surface water, 0-1 493.6
      ng x g(-1) for SPM and 30.0-245.0 ng x L(-1) for groundwater, with averages of
      335.3 ng x L(-1), 382.9 ng x L(-1), and 104.4 ng x L(-1), respectively. The
      logarithm in situ SPM-water partition coefficients (lg k(oc)) of AT were in the
      range of 3.50-4.14 indicating that adsorption of AT from the aqueous phase to SPM
      plays an important role in dissipating AT in surface water. Fluxes of AT in
      surface water ranged from 1.5-184.7 mg x s(-1) in the basin, calculated based on
      the measured flow velocity and concentrations in surface water and SPM. The
      maximum value of AT flux was found in the middle stream of the Taizi River (S7).
      The risk assessment suggested that the ecological risk of AT in surface water was
      low, with more than 95% of the species protected from risk in the Taizi River
      basin. However, the residue levels of AT in surface water of the Taizi River
      basin may cause potential environmental risks.

PMID- 24946575
TI  - [Development of a method for measuring dissolved reactive phosphorus (DRP) and
      dissolved ferrous iron in large batch in pore water samples of sediments with
      micro-volumes].
AB  - A method was established to measure the concentrations of dissolved reactive
      phosphate (DRP) and dissolved ferrous iron (Fe) in micro-volume solution samples
      through colorimetric determination in large batch using a 384-well Microplate
      Spectrophotometer. Concentrations of DRP and dissolved Fe were determined by the
      molybdenum blue and phenanthroline colorimetric methods, respectively. The
      results showed that the sample consumption used for each parameter was between 20
      and 50 microL after dilution, and the detection limits for DRP and dissolved Fe
      were 0.006 mg x L(-1) and 0.010 mg x L(-1) respectively, while the analytical
      precision varied between 1% and 5%. The established method was applied to measure
      DRP and dissolved Fe in pore waters of sediment profiles in Lake Taihu, which
      were collected by a high-resolution Peeper (HR-Peeper) device with a vertical
      resolution of 2 mm. The results showed a simultaneous increase of DRP and
      dissolved Fe in their concentrations with the depth of two sediment profiles
      investigated.

PMID- 24946576
TI  - [Temporal and spatial variation of water nutrient level after exogenous nutrient
      input].
AB  - In order to study the spatial and temporal variations of nitrogen (N) and
      phosphorous (P) nutrition in artificial wetlands after a single exogenous
      nutrient input, 6 mosaic communities of 7 plant species were set up in a cement
      channel in the greenhouse. After the addition of N and P nutritional solutions,
      the concentrations of dissolved total nitrogen (DTN), dissolved total phosphorous
      (DTP), ammonia nitrogen (NH4(+)-N), nitrate nitrogen (NO3(-) -N) and nitrite
      nitrogen (NO2(-) -N) in the surface, middle, and bottom layers of the bulk water
      were determined regularly within 22 days. The results show that: (1) the water
      depth and measuring date have significant effects on nutritional contents while
      the type of plant communities have no such an influence; (2) the diffusion of
      nutrient from surface to the middle water layers is relatively slow, which costs
      6 days under the current experimental condition; (3) in the bottom water layer,
      nutritional concentrations had no significant changes except for NO2-N, thus the
      exogenous nutrient input mainly affects the nutrient contents of surface and
      middle-level bulk water; (4) DTP and NH4(+) -N contents gradually decline to
      similar levels that before the nutritional input event until the end of
      experimental period, though DTN and NO3(-) -N content decrease much more slowly;
      (5) the fact that NO2(-) -N contents rise in water layers of all depths
      demonstrates that nitrification and denitrification in the process of N
      circulation are enhanced. It is concluded that exogenous nutrient inputs not only
      harm aquatic ecosystems but also directly threat human health.

PMID- 24946577
TI  - [Physical process based risk assessment of groundwater pollution in the mining
      area].
AB  - Case studies of groundwater pollution risk assessment at home and abroad
      generally start from groundwater vulnerability, without considering the influence
      of characteristic pollutants on the consequences of pollution too much.
      Vulnerability is the natural sensitivity of the environment to pollutants. Risk
      assessment of groundwater pollution should reflect the movement and distribution
      of pollutants in groundwater. In order to improve the risk assessment theory and
      method of groundwater pollution, a physical process based risk assessment
      methodology for groundwater pollution was proposed in a mining area. According to
      the sensitivity of the economic and social conditions and the possible
      distribution of pollutants in the future, the spatial distribution of risk levels
      in aquifer was ranged before hand, and the pollutant source intensity
      corresponding to each risk level was deduced accordingly. By taking it as the
      criterion for the classification of groundwater pollution risk assessment, the
      groundwater pollution risk in the mining area was evaluated by simulating the
      migration of pollutants in the vadose zone and aquifer. The result show that the
      risk assessment method of groundwater pollution based on physical process can
      give the concentration distribution of pollutants and the risk level in the
      spatial and temporal. For single punctuate polluted area, it gives detailed risk
      characterization, which is better than the risk assessment method that based on
      aquifer intrinsic vulnerability index, and it is applicable to the risk
      assessment of existing polluted sites, optimizing the future sites and providing
      design parameters for the site construction.

PMID- 24946578
TI  - [Hydrogeochemical characteristics of a typical karst groundwater system in
      Chongqing].
AB  - The two-year hydrologic process, hydrochemistry, and a portion of deltaD,
      delta18O of both the surface water at the inlet and the groundwater at the
      outlet, were investigated to identify the spatial and temporal variations of
      hydrogeochemistry in the Qingmuguan karst groundwater system. Research results
      show that there are wet and dry periods in the groundwater system owing to the
      striking influence of seasonal rainfall. The evolution of the chemical
      compositions in the groundwater is significantly influenced by the water and rock
      interaction, anthropogenic activities and rainwater dilution. The variations of
      the chemical compositions in the groundwater exhibit obvious spatiality and
      temporality. The deltaD and delta18O of the surface water beneath the local
      Meteoric Water Line of Chonqing indicate that the surface water is strongly
      evaporated. Furthermore, the deltaD and delta18O of the surface water are more
      positive in the dry period than in the wet period, showing a distinct seasonal
      effect. The deltaD and delta18O of the groundwater are quite stable and much
      negative compared with those of the surface water, which suggests that the
      rainwater recharge the groundwater via two pathways, one directly through
      sinkholes and the other via the vadose zone.

PMID- 24946579
TI  - [Investigation of nitrogen, phosphorus and microbial contamination in Laolongdong
      underground river system of Chongqing].
AB  - With urbanization, groundwater in China has been widely polluted. Karst
      groundwater is important in southwest China, and would be difficult to recover
      once contaminated. NO3(-), PO4(3), NH4(+), total coliform, total E. coli and
      fecal coliform were chosen as indexes in the study of groundwater of Laolongdong
      Underground River System in Nanshan Mountain, Chongqing. After a few years of
      survey, the results showed that NO3(-), NH4(+) and PO4(3-) concentrations in the
      water were all above the nature value, especially NH4(+) and PO4(3-). The NO3(-)
      concentration of Guihuawan spring ranged from 19.78-68.55 mg x L(-1), in some
      months, above the recommended water quality guideline (50 mg x L(-1)) according
      to Standards for Drinking Water Quality set by World Health Organization. NH4(+)
      and PO4(3-) concentrations in Laolongdong underground river varied from 2.71
      12.92 mg x L(-1) and 0.16-11.22 mg x L(-1). The NO3(-) concentration in
      Laolongdong underground river was lower than in karst spring; however, the
      concentrations of NH4(+) and PO4(3-) were higher than in the spring. It seemed
      that the NO3(-) concentration tended to decrease from 2008 to 2013 in the
      underground river caused by urbanization, reduction of farmland and reducing
      environment. However, waste water with a high PO4(3-) concentration led to an
      increasing trend in the PO4(3-) concentration in underground river. Microbial
      contamination was extremely serious, and even far exceeded class V of water
      quality standards of China. For example, the concentration of fecal coliform in
      the groundwater ranged from 3.4 x 10(4)-3.68 x 10(4) CFU x mL(-1). Because of the
      special hydrogeological structure, karst depressions, skylights and sinkholes can
      lead pollutants easily to the underground water. Agriculture activity, sewage
      from towns, enterprises and residential areas were the major sources of nitrogen,
      phosphorus and microbial contamination.

PMID- 24946580
TI  - [Effects on phosphorus fraction distribution in sediment by roots of Vallisneria
      natans].
AB  - The present study explored phosphorus fractions in sediments with the growth of
      Vallisneria natans. Sediment samples in different layers were collected at 20, 50
      and 80 d, and vertical change of several phosphorus fractions were measured in
      the samples. The root distributions and biomass of the V. natans were measured.
      Our results showed that roots were distributed between 0 and 14 cm in the
      experimental device. The average number of roots and average root length were 58
      and 5.86 cm. After 80 days growth, the percentage of V. natans root biomass were
      45.99%, 32.75%, 16.03% and 5.23% in the sediment with depths of 0-3, 4-6, 7-10
      and 11-14 cm. Total phosphorus (TP) content, phosphorus extracted by NaOH (NaOH
      P), and organic phosphorus (OP) levels remarkably decreased (P < 0.05) in the
      area with a high concentration of tape grass roots. The content of phosphorus
      extracted by HCl (HCl-P), and inorganic phosphorus (IP), showed no significant
      difference (P > 0.05). The results suggest that V. natans root affects the
      migration and transformation of phosphorus species in the sediment.

PMID- 24946581
TI  - [Modeling nitrogen transformation in a novel circular-flow corridor wetland].
AB  - Nitrogen transformation and removal in a novel circular-flow corridor (CFC)
      wetland was simulated. A computer model covering 6 nitrogen forms, 3 media and 10
      transferring pathways, was developed. The results show that the TN removal is
      attributed to zeolite adsorption (53.3%), plants NH4(+) -N uptake (27.6%),
      denitrification (10.2%), plants NO3(-) -N uptake (2.9%) and short-cut
      denitrification (1.5%). The major removal pathway for NH4(+) -N varies from
      season to season. In January, the zeolite adsorption played the most important
      role in NH4(+) -N removal with a contribution of 84.5%. From April to June, the
      plants uptake accounted for 76.4%-85.3% NH4(+) -N removal. While in July, there
      were three removal pathways, namely zeolite absorption (36.1%), nirtosation
      (45.8%) and plants uptake (21.4%), playing an important role in nitrogen
      removals. Additionally, regular plants harvesting, periodical zeolite
      regenerating and aquatic plants growing can improve the TN removal rate by 1.7%
      7.7%, 43.1%-72.2% and 19.8%-36.2%, respectively. In short, it is by the diverse
      removal pathways in CFC wetland that nitrogen can be continuously removed.

PMID- 24946582
TI  - [Natural attenuation of tetracycline in the water of Taihu Lake under different
      environmental conditions].
AB  - Tetracycline (TC) has been widely used in veterinary medicines and disease
      treatments, and has been discharged into nature system due to manure application.
      To know the harmfulness of TC residues, and to investigate the natural
      attenuation of TC under different environmental conditions, simulated attenuation
      experiments in the presence of light, sediment, Cd (NO3) 2 and Pb(NO3)2 were
      performed. Results showed that the natural attenuation of TC was not obvious
      under the sunlight, and the natural attenuation rate of TC in water with
      unsterilized sediment was greater than that with sterilized sediment. The natural
      attenuation of TC in water with Pb(NO3)2 was slow at the first stage of the
      experiment, and progressively speeded up as time went on. However, the natural
      attenuation of TC in water with Cd(NO3)2 was more rapid at the beginning, and
      significantly faster than that of Pb(NO3)2. The natural attenuation rates of 0.08
      mmol x L(-1) TC under different conditions follow the sequence: unsterilized
      sediment (87.2%) > sterilized sediment (70.37%) > Cd(NO3)2 (64.2%) > Pb(NO3)2
      (32.3%) > blank (6.6%), suggesting that all these factors can promote the natural
      attenuation of TC. Though the natural attenuation trend under different
      conditions in the dark is similar to that under the sunlight, the natural
      attenuation rate is less than that under the sunlight, which implicates that
      sunlight may promote the natural attenuation of TC.

PMID- 24946583
TI  - [Inactivation and reactivation of antibiotic-resistant bacteria during and after
      UV disinfection in reclaimed water].
AB  - Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned
      as an emerging contaminant. To estimate inactivation and reactivation potentials
      of antibiotic-resistant bacteria by UV disinfection, inactivation and
      reactivation of penicillin-, ampicillin-, cephalexin-, chloramphenicol-and
      rifampicin-resistant bacteria in the secondary effluent were studied under
      different UV doses. The results showed that the inactivation ratios of penicillin
      , ampicillin-, cephalexin-and chloramphenicol-resistant bacteria were higher than
      4-log, which was closed to that of total heterotrophic bacteria; however, the
      inactivation ratio of rifampicin-resistant bacteria was lower (3.7-log) under 20
      mJ x cm(-2) UV exposure. After 22 h standing incubation, antibiotic-resistant
      bacteria widely reactivated. The colony forming ability of antibiotic-resistant
      bacteria was as high as 3-log when exposed to 20 mJ x cm(-2) UV light. Hence,
      conventional UV dose can not effectively control reactivation of antibiotic
      resistant bacteria in reclaimed water by UV disinfection.

PMID- 24946584
TI  - [Photoreactivation of Escherichia coli and Enterococcus faecalis in the secondary
      effluent disinfected by UV-TiO2].
AB  - Effects of photoreactivating light intensity (0-41 microW x cm(-2)) on
      photoreactivation of Escherichia coli (E. coli) and Enterococcus faecalis (E.
      faecalis) in the secondary effluent after UV and UV-TiO2 disinfection were
      investigated. The results indicated that the disinfection efficiency of UV-TiO2
      was much higher than that of UV disinfection. The photoreactivation rate of E.
      coli was much higher in UV disinfection than that in UV-TiO2 disinfection. Under
      high light intensity in UV-TiO2 disinfection, high resurrection rate can be
      induced. However, a higher resurrection rate can be introduced even under low
      light intensity in the UV disinfection. Meanwhile, UV-TiO2 disinfection had a
      strong inhibition effect on E. faecalis photoreactivation, when the light
      intensity was lower than 21 microW x cm(-2), three was no resurrection occurred
      on E. faecalis after 72 h resurrection irradiation, only under a strong
      photoreactivating light intensity, the resurrection rate of E. faecalis was
      observed.

PMID- 24946585
TI  - [Stability of C60 nanoparticles in aquatic systems].
AB  - The influences of storage time, pH, electrolytes and organic matters on the
      stability of two different suspensions of C60 nanoparticles were investigated.
      The results showed that the C60 nanoparticles prepared by solvent substitution
      (C60/son) were more stable than that prepared by prolonged stirring (C60/aq), and
      kept stable for a period of time. Higher pH enhanced the stability of C60
      nanoparticles. The presence of electrolyte made a dramatic decrease in the
      surface zeta potential and an increase in the particle size. The aggregation
      process of C60 nanoparticles exhibited slow and rapid regions, which was found to
      be consistent with the classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of
      colloidal stability. The critical coagulation concentration (CCC) values of
      C60/son, obtained from the intersection of the interpolated lines through the
      slow and fast regions, were estimated as 321 mmol x L(-1) NaCl, 316 mmol x L(-1)
      KCl, 9.6 mmol x L(-1) MgCl2 and 6.7 mmol x L(-1) CaCl2. The CCC values of C60/aq
      were estimated as 295 mmol x L(-1) NaCl, 278 mmol x L(-1) KCl, 7.8 mmol x L(-1)
      MgCl2 and 5.9 mmol x L(-1) CaCl2, which were much higher than their
      concentrations in natural waters. The presence of humic acid enhanced the
      stability of C60 nanoparticles, which was attributable to steric repulsion.
      Therefore, C60 nanoparticles will keep relatively stable in typical aquatic
      environments.

PMID- 24946586
TI  - [Fouling behavior of sodium alginate during microfiltration at various ionic
      compositions: XDLVO approach].
AB  - The extended Derjaguin-Laudau-Verwey-Overbeek (XDLVO) theory was utilized to
      quantitatively evaluate short-range interfacial interactions involved in
      microfiltration (MF) membrane fouling by sodium alginate (SA) at various ionic
      compositions. Results showed that for hydrophilic membrane surfaces, van der
      Waals interactions facilitated fouling, whereas acid-base interactions alleviated
      fouling; for hydrophobic membrane surfaces, however, van der Waals interactions
      mitigated fouling and acid-base interactions turned out to be favorable for
      fouling. Electrostatic double layer interactions contributed minimally to fouling
      when SA molecules came into contact with MF membrane surface. Ionic strength and
      Ca2+ affected SA fouling of MF membranes mainly through alteration of acid-base
      interactions between membrane and SA or among SA themselves. Higher ionic
      strength could make acid-base interaction less repulsive or more attractive, thus
      aggravating SA fouling of MF membrane. Although Ca2+ accelerated flux decline
      significantly, Ca2+ could enhance physical cleaning efficiencies. Under all
      tested ionic compositions, fouling potentials (K) of initial and subsequent
      stages correlated well with membrane-SA interfacial free energy of adhesion and
      SA-SA interfacial free energy of cohesion, respectively. This implies that the
      XDLVO theory is applicable for description of MF membrane fouling by SA at
      various ionic compositions.

PMID- 24946587
TI  - [Enhanced remediation of 4-chloronitrobenzene contaminated groundwater with
      nanoscale zero-valence iron (nZVI) catalyzed hydrogen peroxide (H2O2)].
AB  - Chemical oxidation-reduction technology is an important way to quickly remedy
      contaminated groundwater. Nanoscale zero-valent iron (nZVI) was produced by
      liquid-phase reduction using FeSO4 and NaBH4, and characterized by SEM and XRD.
      The remediation of 4-chloronitrobezene (4-CINB) contaminated groundwater at
      ambient temperature and pressure was conducted with the nZVI catalytic H2O2
      process, and the affecting factors and degradation mechanisms were investigated.
      The results indicated that under initial pH 3.0 at the temperature of 30 degrees
      C, after 30 mins of reaction, 4-ClNB in groundwater was completely degraded when
      the concentrations of nZVI and H2O2 were 268.8 mg x L(-1) and 4.90 mmol x L(-1),
      respectively. 4-chloronitrosobenzene, 4-chlorophenylhydroxylamine, 4
      chloroazoxybenzene, 4-chloroaniline, 4-chloroazobenzene, 4-benzoquinone, acetic
      acid, formic acid, oxalic acid and chlorine ion were identified as the major
      intermediates of 4-ClNB degradation after the process. A tentative pathway for
      the degradation of 4-ClNB was proposed.

PMID- 24946588
TI  - [Effect of the coexistence of chlorobenzene homologue on anaerobic degradation of
      hexachlorobenzene].
AB  - The anaerobic biodegradation of hexachlorobenzene is being an intensively studied
      technology for contaminated soil remediation. The effect of three coexisting
      chlorobenzene homologue (pentachlorobenzene, 1, 2, 4, 5-tetrachlorobenzene and 1,
      2, 4-trichlorobenzene) on anaerobic degradation of hexachlorobenzene in dye
      processing industry contaminated soil was studied under different environmental
      conditions such as initial pH, reaction temperature and solid-liquid ratio. The
      result showed that the anaerobic degradation activity of hexachlorobenzene was
      reduced due to the feedback inhibition caused by accumulation of chlorobenzene
      homologue. The feedback inhibition and accumulation may vary based on different
      environmental conditions. Pentachlorobenzene exhibited the strongest inhibitive
      effect compared to the other two chlorobenzene homologue with low initial pH
      values, at room temperature and low solid-liquid ratio, respectively. Whereas 1,
      2, 4-trichlorobenzene significantly inhibited the degradation with high initial
      pH values and at higher temperature. As a conclusion, optimization of
      environmental conditions and reduction of chlorobenzene homologue accumulation in
      the process can enhance the degradation of hexachorobenzene in contaminated soil.

PMID- 24946589
TI  - [Research on removal efficiency of Cd (II)-bearing wastewater by sulfate-reducing
      biological filter].
AB  - At the temperature of 18.0-22.3 degrees C, biological carriers were produce from
      pure SRB and zeolite by the embedding immobilized method, and a sulfate-reducing
      biological filter filled with filter carriers was built to treat cadmium
      containing wastewater. Experimental research on removal efficiency of Cd2+, COD
      and SO4(2-) in wastewater by the biological filter was carried out after SRB
      domestication. Results show that cadmium can be removed satisfactorily from
      wastewater using SRB by the biological filter filled with sulfate-reducing
      bacteria. When the filtration rate was 0.4 m x h(-1) and the cadmium
      concentration in wastewater was not more than 15 mg x L(-1), the processing
      efficiency was the best. In the formal running period, the removal rates of Cd2+,
      COD and SO4(2-) by the biological filter were more than 99%, 75% and 50%. The
      effluent Cd2+ concentration was less than 0.1 mg x L(-1), which could meet the
      cadmium emission requirements in the wastewater quality standards for discharge
      to municipal sewers (CJ 343-2010). The removal of Cd2+, COD and SO4(2-) by
      biological filter mainly occurs in the top 60 cm of the filter bed during stable
      operation. When the filtration rate was less than 0.6 m x h(-1), Cd(2+) can be
      removed by the biological filter with high efficiency and stability.

PMID- 24946590
TI  - [Control strategies of nitrogen removal process in a pilot test of the southern
      WWTP based on the nitrogen balance].
AB  - By building the mass balance of nitrogen in A2/O process, the nitrogen model
      which raised some strategies on how to control sludge return ratio and mixed
      liquid return ratio to make the effluent nitrogen achieve the national standard A
      under different influent total nitrogen (TN) , was set up. And the presumed
      parameters were verified by the pilot test of the Wuhan's Longwangzui WWTP. The
      result showed that when the temperature and the TN were over 15 degrees C and
      below 30 mg x L(-1) respectively, the mixed liquid return ratio was 0. When the
      temperature was between 10 degrees C and 15 degrees C and TN was over 30 mg x L(
      1), higher MLSS and DO elevated N removal. When the temperature was far below 10
      degrees C, the mixed liquid return ratio was also at a higher level. Based on the
      Wuhan's Longwangzui WWTP influent water quality, measures of adjusting the return
      ratio were well adapted to obtain acceptable nitrogen effluent.

PMID- 24946591
TI  - [Effect of simulated inorganic anion leaching solution of electroplating sludge
      on the bioactivity of Acidithiobacillus ferrooxidans].
AB  - An Acidithiobacillus ferrooxidans strain WZ-1 (GenBank sequence number: JQ968461)
      was used as the research object. The effects of Cl-, NO3-, F- and 4 kinds of
      simulated inorganic anions leaching solutions of electroplating sludge on the
      bioactivity of Fe2+ oxidation and apparent respiratory rate of WZ-1 were
      investigated. The results showed that Cl-, NO3(-)- didn't have any influence on
      the bioactivity of WZ-1 at concentrations of 5.0 g x L(-1), 1.0 g x L(-1),
      respectively. WZ-1 showed tolerance to high levels of Cl- and NO3- (about 10.0 g
      x L(-1), 5.0 g x L(-1), respectively), but it had lower tolerance to F- (25 mg x
      L(-1)). Different kinds of simulated inorganic anions leaching solutions of
      electroplating sludge had significant differences in terms of their effects on
      bioactivity of WZ-1 with a sequence of Cl-/NO3(-)/F(-) > or = NO3(-)/F(-) > Cl
      /F(-) > Cl(-)/NO3(-).

PMID- 24946592
TI  - [Microbial reduction of Cu2+ mediated by electroactive biofilms].
AB  - The formation, electron transfer mechanism and environmental effect of
      electrochemically active biofilms (EABs) have become a hot research topic in
      environmental science. In this study, bacteria were enriched on a carbon felt to
      form an EAB under controlled potential conditions. The electrochemical properties
      of the EAB were evaluated with electrochemical methods. The process of copper
      reduction and transformation mediated by the EAB was revealed. Analytical
      techniques such as scanning electron microscopy (SEM), energy dispersive
      spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) were used to
      examine the morphology, content and state of copper in the biofilm. The results
      showed that the EAB could utilize acetate as electron donor to produce electrons
      and Cu2+ was reduced to Cu or Cu+. Laser scanning confocal microscope (LSCM) was
      employed to probe the toxic effects of Cu2+ on the EAB. Copper toxicity on the
      microbes was reduced in the presence of acetate because of the reduction
      transformation of Cu2+ to less toxic Cu or Cu+. The results from this study are
      expected to be instructive for using EABs to stabilize and recover copper from
      copper-contaminated environments.

PMID- 24946593
TI  - [Copper recovery from artificial bioleaching lixivium of waste printed circuit
      boards].
AB  - The key step to realize metal recovery from bioleaching solutions is the recovery
      of copper from bioleaching lixivium of waste printed circuit boards in high-grade
      form. The influences of cathode material, current density, initial pH and initial
      copper ion concentration on the efficiency and energy consumption of copper
      recovery from artificial bioleaching lixivium under condition of constant current
      were investigated using an electro-deposition approach. The results showed that
      the larger specific surface area of the cathode material (carbon felt) led to the
      higher copper recovery efficiency (the recovery efficiencies of the anode and the
      cathode chambers were 96.56% and 99.25%, respectively) and the smaller the total
      and unit mass product energy consumption (the total and unit mass product energy
      consumptions were 0.022 kW x h and 15.71 kW x h x kg(-1), respectively). The
      copper recovery efficiency and energy consumption increased with the increase of
      current density. When the current density was 155.56 mA x cm(-2), the highest
      copper recovery efficiencies in the anode and cathode chambers reached 98.51% and
      99.37%, respectively. Accordingly, the highest total and unit mass product energy
      consumptions were 0.037 kW x h and 24.34 kW x h x kg(-1), respectively. The
      copper recovery efficiency was also significantly affected by the initial copper
      ion concentration. The increase of the initial copper ion concentration would
      lead to faster decrease of copper ion concentration, higher total energy
      consumption, and lower unit mass product consumption. However, the initial pH had
      no significant effect on the copper recovery efficiency. Under the optimal
      conditions (carbon felt for cathode materials, current density of 111.11 mA x cm(
      2), initial pH of 2.0, and initial copper ion concentration of 10 g x L(-1)), the
      copper recovery efficiencies of the anode and cathode chambers were 96.75% and
      99.35%, and the total and unit mass product energy consumptions were 0.021 kW x h
      and 14.61 kW x h x kg(-1), respectively. The deposited copper on the cathode
      material was fascicularly distributed and no oxygen was detected.

PMID- 24946594
TI  - [Difference of contaminant composition between landfill leachates and groundwater
      and its reasons].
AB  - In order to investigate the groundwater pollution by landfill leachates, the
      distribution characteristics of inorganic salt, organic compounds and heavy
      metals in leachastes from a simple landfill and groundwater and its reason were
      study using conventional analysis, fluorescence excitation-emission matrix
      spectra and multivariate statistical analysis. The results showed that the
      landfill was heterogeneous, and the extracts from the landfill wastes showed a
      high concentration of NH4(+) -N, but low contents of Cl-, SO4(2-), dissolved
      organic matter (DOM) and heavy metals. The nitrification process was blocked due
      to a strong reducing atmosphere in landfill, which caused a low concentration of
      NO3(-) -N and NO2(-) -N in leachates. Cu was mainly associated with DOM in
      leachates, while the distribution of the metals Ba, Cd, Cr, Fe, Mn, Ni, Zn and As
      was primarily related to hydrophobic organic compounds. The contaminate
      compositions in different groundwater were similar except for the groundwater
      under the landfill site. In contrast to landfill leachates, the groundwater
      showed a low concentration of NH4(+) -N, but high concentrations of Cl-, SO4(2-),
      DOM, NO3(-) -N and NO2(-) -N except for the groundwater under the landfill site.
      The organic compounds in the groundwater were mainly originated from microbial
      activity, and the distribution of the metals Ba, Cd, Cu, Fe, Mn and Ni was mainly
      related to fluorescecent organic matter in DOM. The results showed that the leak
      point of landfill leachates can be identified through the cluster analysis method
      on the basis of the contaminant composition in groundwater.

PMID- 24946595
TI  - [Photochemical degradation of landfill leachate facilitated by combined
      schwertmannite and H2O2].
AB  - It is practically important that high concentrations of organic pollutants in
      landfill leachate were degraded by a rapid and efficient approach. The influence
      of operating conditions such as schwertmannite dosage, V(H2O2)/m (schwertmannite)
      ratio on the degradation efficiency of color, TOC and COD contents of landfill
      leachate, was investigated by using the schwertmannite/H2O2/UV process. It was
      demonstrated that the color, TOC and COD removal efficiencies increased
      significantly with the increase in schwertmannite dosage, and then were
      approximately stable. However, COD removal efficiency declined because of the
      presence of the residual H2O2 when V (H2O2)/m (schwertmannite) was greater than
      2, and the best removal efficiency of COD was 44.9%. Furthermore, high-intensity
      ultraviolet was more conducive to eliminate pollutants through photochemical
      oxidation with schwertmannite/H2O2. The color, TOC and COD removal efficiencies
      were 90.0%, 78.8% and 52.6% respectively after 2.5 hours of photochemical
      degradation, with UV-500 W under optimal initial pH = 2.5; meanwhile, this study
      found that it was beneficial to the photochemical degradation of leachate at room
      temperature via the schwertmannite/H2O2/UV process, and COD removal efficiency
      declined gradually when the temperature was higher than 25 degrees C. Controlled
      trials showed that the schwertmannite/H2O2 method was conducive to the removal of
      color compared with the traditional homogeneous Fenton reaction.

PMID- 24946597
TI  - [Comparative study on biological methane potential and methanogen biodiversity in
      the anaerobic digestion of excess sludge].
AB  - AP and DH excess sludge, sampled from AP and DH wastewater treatment plants
      respectively, were inoculated with their anaerobic sludge respectively and tested
      with biological methane potential (BMP) method. After the regression analysis
      with modified Gompertz and Michaelis-Menten model, it was found that although the
      maximum specific CH4 production rates of AP and DH anaerobic sludge were similar
      [74.21 and 51.99 mL x (g x d)(-1)], the half-saturation constants K(m) differed
      obviously (54098 and 19005 mg x L(-)), indicating DH anaerobic sludge exhibited a
      higher affinity for its excess sludge. At the end of both BMP tests, the
      concentrations of TSS and COD(T) decreased while the concentration of NH4(+)-N
      increased obviously, which were more significant at higher ratios of F/M. The T
      RFLP analysis results were in accordance with BMP tests. After both BMP tests,
      the relative amount of diverse bacteria decreased while the relative amounts of
      Methanosaeta spp. (280 bps), Methanomicrobiaceae (80 bps) and RC-I (389 bps)
      increased obviously, which were more significant in DH-BMP test compared with AP
      BMP.

PMID- 24946596
TI  - [Effects of operating parameters on organic toxicity of sludge treating synthetic
      bisphenol A wastewater].
AB  - In order to investigate the influence of hydraulic retention time (HRT) and
      sludge retention time (SRT) on sludge organic toxicity in sequencing batch
      reactors (SBR(S)), the sludge toxicity was compared when HRT and SRT were
      controlled at various levels. The influents COD were controlled at around 300 mg
      x L(-1), HRT and SRT were changed from 12 h to 8 h and from 20 d to 10 d,
      respectively. The effluents COD, BPA contents both in liquid and sludge were
      measured, and sludge toxicity was also analyzed and compared between the blank
      group (no BPA content) and BPA control groups (40 mg x L(-1)). The results showed
      that the effluents COD of two SBRs were both below 50 mg x L(-1), and there were
      no BPA content in liquid and sludge. Furthermore, decrease HRT and SRT is helpful
      to remove BPA and reduce sludge toxicity. Additional investigation revealed a
      correlation between the properties of bacterial community and total sludge
      toxicity by the PCR-DGGE analysis, and different influent compositions and
      operation parameters were the main reasons for leading the difference of sludge
      toxicity.

PMID- 24946598
TI  - [Isolation and identification of Mn oxidizing bacterium Aminobacter sp. H1 and
      its oxidation mechanism].
AB  - A bacterium with high manganese oxidizing activity was isolated from a biological
      manganese removal filter and named as H1. Based on its characteristics and the
      analysis of 16S rDNA sequence, the strain H1 belonged to the genus Aminobacter
      sp. and its manganese oxidizing ability had never been reported. In this paper,
      the microbiologic properties of the strain H1, the manganese oxidation mechanisms
      and characteristics of biogenic manganese oxides were investigated. The results
      showed that the maximal tolerant Mn concentration of strain H1 was 50 mmol x L(
      1), and Mn(II) could be completely removed by strain H1 when the concentration
      was lower than 10 mmol x L(-1). Strain H1 could oxidize Mn2+ by both the
      production of manganese oxidizing activity factor and alkaline metabolites during
      growth, which were synthesized in the cell and then secreted into extracellular
      culture medium. During the oxidation process, the intermediate of soluble Mn(III)
      was detected. SEM showed that the biogenic manganese oxides were amorphous and
      poorly-crystalline, and it closely combined with bacteria. The components of the
      biogenic manganese oxides produced by strain H1 were identified as MnCO3, MnOOH,
      Mn3O4 and MnO2 by XRD, XPS and SEM-EDX.

PMID- 24946599
TI  - [Nitrate removal by a strain of nitrate-dependent Fe (II) -oxidizing bacteria].
AB  - A nitrate-dependent Fe(II)-oxidizing bacterial strain, named W5, was isolated
      from the sediment of the East Lake in Wuhan. Strain W5 was studied for its
      characteristics of denitrification and nitrogen removal. According to its
      physiological and biochemical characteristics and the analysis of its 16S rRNA
      gene sequence, strain W5 was identified as Microbacterium sp. The optimal
      denitrification performance can be obtained under conditions of NO3(-) -N 40 mg x
      L(-1), Fe2+ 500 mg x L(-1) and pH 6.8-7.0. After one week of cultivation under
      optimal conditions, nitrate removal percentage reached 87.0%. During the process
      of the culture, the nitrite nitrogen concentration was no more than 0.31 mg x L(
      1) and there was no ammonia nitrogen production. It was indicated that the
      nitrate was mostly converted into N2. The consumption rate of Fe2+ was 95.2%.

PMID- 24946600
TI  - [Study on the iopromide-degrading characteristics of strain Pseudomonas sp. I-24
      via co-metabolism].
AB  - Strain Pseudomonas sp. I-24 (I-24) cannot utilize iopromide (IOP) as the sole
      carbon and energy source, so different carbon sources (starch, malt sugar,
      glucose and glycerol) were used as the additional carbon sources to study their
      effects on I-24 growth and IOP degradation in flask tests. The results showed
      that the IOP degradation process by I-24 matched the first-order kinetics. Among
      these four co-substrates, starch was found to be the most efficient to enhance
      IOP degradation. The corresponding degradation efficiency was as high as 92.7%
      and the highest enzymatic activity of 0.182 mU appeared in the third day. The
      optimum starch concentration was 1 g x L(-1). Since glucose and malt sugar better
      promoted I-24 growth and electron transport system activity (ETSA), indicating
      that the IOP degradation process would probably be restrained by excess growth,
      which decreased the degradation efficiency of IOP. In addition, no direct
      correlation between ETSA and co-metabolism process was found. The detected
      enzymatic activity of I-24 in control sample indicated that the key enzymes could
      be still induced in low-concentration of co-substrates.

PMID- 24946601
TI  - [Using flow cytometry to explore the changes of Sphingomonas sp. GY2B bacterial
      surface characteristics in the process of degrading phenanthrene].
AB  - The first step of biodegradation is the contact of microorganism and pollutants,
      in order to examine the influence of phenanthrene on Sphingomonas sp. GY2B's
      surface properties during its degrading process, the bacteria was cultivated at
      different conditions, and detected by flow cytometry combined with fluorescent
      dyes for its surface changes. The results indicated that, the membrane structure
      had been certainly damaged during the degrading process, leading to an increased
      membrane permeability. Moreover, the destruction of bacteria membrane integrity
      became more serious with a higher pollutant concentration. At the concentration
      of 300 mg x L(-1), the ratio of stained bacterial cells/unstained cells was 12.44
      after cultured for 60 h, while at 100 mg x L(-1) and 1.2 mg x L(-1), the ratios
      were 1.95 and 1.11, respectively. The results of fourier transform infrared (FT
      IR) absorbance spectroscopy detection, the discrimination of death, injured and
      intact cells, and Zeta potential detection further verified the bacterial cell
      surface permeability changes. Flow cytometry combined with fluorescent dye
      propidium iodide was used to monitor the changes of bacterial membrane integrity
      on single-cell level which exhibited a good potential for exploring the changes
      of bacterial surface properties during the degrading progress and more deeply for
      investigating the degradation mechanism.

PMID- 24946602
TI  - [Research on characteristic of interrelationship between toxic organic compound
      BPA and Chlorella vulgaris].
AB  - The effects of different concentrations of bisphenol A (BPA) on Chlorella
      vulgaris and removal capacity of BPA by Chlorella vulgaris were investigated.
      Results showed that a low concentration (0-20 mg x L(-1)) of BPA promoted the
      growth of Chlorella vulgaris, whereas a relative high concentration (20-50 mg x
      L(-1)) of BPA inhibited the growth of Chlorella vulgaris, and the inhibition
      effect was positively correlated with the concentration of BPA. Likewise, a high
      dose of initial BPA (> 20 mg x L(-1)) led to a decline in the content of
      chlorephyll a. Chlorella vulgaris had BPA removal capacity when initial BPA
      concentration ranged from 2 mg x L(-1) to 50 mg x L(-1). There was positive
      correlation between the removal rate of BPA per cell and initial BPA
      concentration. The removal rate of BPA was the highest when initial BPA was 50 mg
      x L(-1), which appeared between lag phase and logarithmic phase.

PMID- 24946603
TI  - [Effect of magnesium deficiency on photosynthetic physiology and triacylglyceride
      (TAG) accumulation of Chlorella vulgaris].
AB  - As an excellent biological resource, Chlorella has wide applications for
      production of biofuel, bioactive substances and water environment restoration.
      Therefore, it is very important to understand the photosynthetic physiology
      characteristics of Chlorella. Magnesium ions play an important role in the growth
      of microalgae, not only the central atom of chlorophyll, but also the cofactor of
      some key enzyme in the metabolic pathway. A laboratory study was conducted to
      evaluate the effects of magnesium deficiency on several photosynthetic and
      physiological parameters and the triacylglyceride (TAG) accumulation of the green
      alga, Chlorella vulgaris, in the photoautotrophic culture process. Chlorella
      vulgaris biomass, protein, chlorophyll a and chlorophyll b contents decreased by
      20%, 43.96%, 27.52% and 28.07% in response to magnesium deficiency, while the
      total oil content increased by 19.60%. Moreover, magnesium deficiency decreased
      the maximal photochemical efficiency F(v)/F(m) by 22.54%, but increased the non
      photochemical quenching parameters qN. Our results indicated the decline of
      chlorophyll caused by magnesium, which affected the photosynthesis efficiency,
      lead to the growth inhibition of Chlorella vulgaris and affected the protein
      synthesis and increased the triacylglyceride (TAG) accumulation.

PMID- 24946604
TI  - [Effects of microcystins on growth and antioxidant system of rice roots].
AB  - The effect of different concentrations (1, 100, 1000 and 3 000 microg x L(-1)) of
      microcystins (MCs) on growth, absorb activity, antioxidant system and its
      accumulation in roots of rice seedlings were studied. The results show that MCs
      accumulation was positively correlated with MCs concentration. After the
      treatment with 1 microg x L(-1) MCs, the root growth and activity increased.
      Meanwhile, catalase (CAT) activity was increased to maintain H2O2 at normal
      levels. After the treatment with 100 microg x L(-1) MCs, the root growth and
      activity were inhibited whereas CAT had no obvious change. High concentrations
      (1000 microg x L(-1) and 3000 microg x L(-1)) of MCs not only inhibited root
      growth and activity, but decreased CAT activity, leading to excessive H2O2
      accumulation and membrane peroxidation. After a 7-day recovery, MCs accumulations
      in roots in all treatment groups were all lower than those measured during the
      stress period. For the 100 microg x L(-1) MCs treated group, the inhibition on
      root growth and root activity, and membrane peroxidation were alleviated, better
      than those measured during the stress period. However, for 1000 microg x L(-1)
      and 3000 microg x L(-1) MCs treated groups, inhibition on root growth, root
      activity, and CAT activity were heavier than those during the stress period, and
      oxidation stress intensified further, indicating that the damage caused by high
      concentrations (1 000 microg x L(-1) and 3000 microg x L(-1)) of MCs on rice
      roots was irreversible.

PMID- 24946605
TI  - [Responses of soybean cultivar Dongsheng-1 to different O3 concentrations in
      northeast China].
AB  - Soybean cultivar Dongsheng No. 1 [Glycine max (L.) Mer.] was exposed to charcoal
      filtered air (CFA), non-filtered air (NFA) and non-filtered air with ozone
      addition (NFA + O3) in nine open-top chambers. Individual yield and yield
      components at maturity, C, N concentration in leaf and seed, gas exchange,
      chlorophyll a fluorescence and pigments content at the full bloom stage were
      measured with an AOT40 value of 10.6 microL x L(-1) x h during the growing
      season. Compared to CFA, NFA reduced individual yield and 100-seed weight by 4.5%
      and 4% respectivley, while NFA + O3 treatment significantly reduced each of them
      by 34% and 18%. However, plant height, node numbers of main stem, pods per plant
      and number of seeds per pod remained unchanged by O3 addition. Leaf C, N
      concentrations at the seed filling stage under NFA + O3 also significantly
      increased by 3% and 26%, respectively, while the CN ratio significantly decreased
      by 18%. Moreover, compared to CFA and NFA, NFA + O3 caused significant reductions
      in the photosynthetic parameters at the full bloom stage, e.g. significant
      declines in net photosynthetic rates, stomatal conductance, water use efficiency,
      fluorescence parameters of F'(v)/F'(m) and phi(PS II). It is proposed that lower
      photosynthetic rates, reduced photochemical efficiency in PS II and the decline
      in 100-seed weight might be the main reasons contributing to the lower individual
      yield of soybean plant by elevated O3.

PMID- 24946606
TI  - [Development and succession of biological soil crusts and the changes of
      microbial biomasses].
AB  - Biological soil crusts (BSCs) play important ecological roles in vegetation and
      ecological restoration in desert regions, and different crust developmental and
      successional stages have different ecological functions. In this experiment, the
      BSCs in Shapotou region (at southeast edge of Tengger Desert) were investigated
      to study crust development and succession through field investigation,
      microscopic observation combined with quantitative analysis of microbial
      biomasses. The results showed that BSCs in this region generally developed and
      succeeded from algal crusts, lichen crusts to moss crusts. With the development
      and succession of BSCs, crust photosynthetic biomass gradually increased, while
      microalgal biomass showed a first increasing and then decreasing trend. Among the
      crust algae (cyanobacteia), Microcoleus vaginatus, as the first dominant species,
      occupied the most algal biomass and reached a maximum of 0.33 mm3 x g(-1) crusts
      in algal crusts; while Scytonema javanicum and Nostoc sp. have their maximal
      biomasses in the later lichen crusts. In addition, it was found that the
      heterotrophic microbial biomass began to increase in algal crusts, and then
      decreased in lichen crusts; followed by another increase and the increase
      achieved the maximum at last in moss crusts. Through the correlation analysis, it
      was found that bacterial biomass significantly positively correlated with crust
      organic carbon and Na+ content, while fungal biomass positively correlated with
      K+ and Na+ content (P < 0.05). In conclusion, this study investigated the
      developmental and successional patterns of BSCs in Shapotou region, and discussed
      the effects of crust development and succession on several microbial biomasses
      from the point of view of environmental adaptation and functional requirement,
      which may be helpful for us to understand crust development and succession, and
      provide theoretical and practical significances for crust maintenance and
      management in ecological restoration of desertification regions.

PMID- 24946607
TI  - [Effects of lead on the growth and reproduction of Eisenia fetida with aged
      soils].
AB  - In this study, effects of Pb (NO3)2 on the growth and reproduction of Eisenia
      fetida were investigated with artificial soils. The results showed that: compared
      with the control group, the growth of E. fetida in contaminated soil was
      inhibited significantly with increasing Pb (NO3)2 concentrations. But there were
      great differences in the extent of inhibition after 0, 7, 28 and 84 days of aging
      in the artificial soils. The most obvious effect occurred in 1000 mg x kg(-1) and
      1500 mg x kg(-1) experimental groups. There was a very big difference in the
      effects of Pb (NO3)2 on reproduction of E. fetida with different aging times. The
      medium effective concentration (EC50)values of cocoon production inhibition were
      1085.10, 1163.32, 1666.86 and 1606.94 mg x kg(-1). In addition, the EC50 values
      of the number of juvenile inhibition were 700.01, 703.88, 1 031.34 and 1 017.89
      mg x kg(-1), respectively. This study indicates that soil aging which affects the
      toxicity of Pb (NO3)2 should be taken into consideration when toxicity tests of
      Pb (NO3)2 were carried out. The results could provide a scientific basis for the
      ecological risk assessment of aging soils and soil environmental quality
      standards.

PMID- 24946608
TI  - [Soil heavy metal cadmium standard limit and range of background value research].
AB  - With the rapid development of industrial and agricultural production in China,
      problems such as excessive soil pollutants worsen year by year, and soil cadmium
      pollution resulting from the emergence of "cadmium rice" and other food security
      incidents occur frequently. It causes the extensive concern of society on soil
      cadmium environmental standards. A soil environmental standard is the foundation
      for the evaluation of soil environmental quality. The maximum allowable value of
      cadmium that affects plant and animal and human health is regarded as the basis
      value all over the world; however, the certification methods and the goals of
      standard application are different, thus the standard limit has a great
      difference. Through the research on domestic and foreign soil cadmium standard
      limits and the soil cadmium background values in China, the soil cadmium
      background content range values of the provinces and of some types of soil are
      given. We report the outstanding problems existing in China's current
      environmental quality standard of soil cadmium. It is proposed that the soil
      environmental quality standard should allow the coexistence of gradient of soil
      cadmium standard limit, effective state and total standard limit, and
      anthropogenic pollution and background values exceeding the standard should be
      strictly distinguished.

PMID- 24946609
TI  - [Study on soil element background values of the Hoh Xil area in north Tibet].
AB  - Hoh Xil locates at northern part of the Tibetan Plateau. Twenty five surface soil
      samples were collected from this area in 2007 and 32 elements were analyzed and
      compared to the element contents of Yarlung Zangbo river sediment, background
      element value of the Tibetan surface soil and the Chinese Continental crust
      contents. The results showed that the element contents of the < 20 microm
      fraction were higher than those of bulk samples; Contents of many elements of
      this study were similar to those of the Tibetan soil. Meanwhile, contents of Ca
      and As of the studied area were higher than those of Chinese continental crust,
      resulting mainly from local alpine arid climate and widely distributed the rocks
      that enriched in As, respectively. The EOF analysis of the contents of bulk soil
      samples revealed the sources and chemical properties of studied elements: many
      elements such as Al, Fe, Ga inherit the characteristics of the parent rocks of
      this region. Meanwhile, elements with an active chemical property and the element
      Zr that specially existed in the heavy minerals also had a certain contribution
      to the contents. The contents of B and Cs revealed contribution of hot springs to
      the soil of studied area.

PMID- 24946610
TI  - [Transfer characteristic and source identification of soil heavy metals from
      water-level-fluctuating zone along Xiangxi River, three-Gorges Reservoir area].
AB  - Transfer characteristics of heavy metals and their evaluation of potential risk
      were studied based on determining concentration of heavy metal in soils from
      water-level-fluctuating zone (altitude:145-175 m) and bank (altitude: 175-185 m)
      along Xiangxi River, Three Gorges Reservoir area. Factor analysis-multiple linear
      regression (FA-MLR) was employed for heavy metal source identification and source
      apportionment. Results demonstrate that, during exposing season, the
      concentration of soil heavy metals in water-level-fluctuation zone and bank
      showed the variation, and the concentration of soil heavy metals reduced in
      shallow soil, but increased in deep soil at water-level-fluctuation zone.
      However, the concentration of soil heavy metals reduced in both shallow and deep
      soil at bank during the same period. According to the geoaccumulation index,the
      pollution extent of heavy metals followed the order: Cd > Pb > Cu > Cr, Cd is the
      primary pollutant. FA and FA-MLR reveal that in soils from water-level
      fluctuation zone, 75.60% of Pb originates from traffic, 62.03% of Cd is from
      agriculture, 64.71% of Cu and 75.36% of Cr are from natural rock. In soils from
      bank, 82.26% of Pb originates from traffic, 68.63% of Cd is from agriculture,
      65.72% of Cu and 69.33% of Cr are from natural rock. In conclusion, FA-MLR can
      successfully identify source of heavy metal and compute source apportionment of
      heavy metals, meanwhile the transfer characteristic is revealed. All these
      information can be a reference for heavy metal pollution control.

PMID- 24946611
TI  - [Heavy metal pollution characteristics and ecological risk analysis for soil
      around Haining electroplating industrial park].
AB  - The pollution status and potential ecological risks of heavy metal in soils
      around Haining electroplating industrial park were studied. Hakanson index
      approach was used to assess the ecological hazards of heavy metals in soils.
      Results showed that average concentrations of six heavy metals (Cu, Ni, Pb, Zn,
      Cd and Cr) in the soils were lower than the secondary criteria of environmental
      quality standard for soils, indicating limited harmful effects on the plants and
      the environment in general. Though the average soil concentrations were low,
      heavy metal concentrations in six sampling points located at the side of road
      still exceeded the criteria, with excessive rate of 13%. Statistic analysis
      showed that concentrations of Cu and Cd in roadside soils were significantly
      higher than those in non-roadside soils, indicating that the excessive heavy
      metal accumulations in the soil closely related with traffic transport. The
      average potential ecological hazard index of soils around Haining electroplating
      industrial park was 46.6, suggesting a slightly ecological harm. However, the
      potential ecological hazard index of soils with excessive heavy metals was 220
      278, suggesting the medium ecological hazards. Cd was the most seriously
      ecological hazard factor.

PMID- 24946612
TI  - [Sources and spatial distribution of typical heavy metal pollutants in soils in
      Xihu Scenic Area].
AB  - Due to the importance as a famous scenic area in China and its special
      geographical position, heavy metal pollution in soils in Xihu Scenic Area has
      attracted great concerns. Typical heavy metals in surface soils (0- 20 cm) in
      Xihu Scenic Area was investigated using the grid sampling method and statistical
      analysis and Aregis approaches. It was suggested that there were anthropogenic
      accumulations of Cu, Zn and Pb in soils, and they were the main heavy metal
      pollutants in Xihu Scenic Area. The contents of Cu, Zn, Pb in soils are in the
      ranges of 4.6-197 mg x kg(-1), 11.1-885 mg x kg(-1) and 11.7-346 mg x kg(-1),
      respectively. The area with the highest 25% of Cu, Pb and Zn content located in
      the north-east part of the scenic area, which had lower ratios of green land,
      dense traffic roads and was characterized with high urbanization. Results of
      multiple comparison among different land uses and spatial cluster and outlier
      analysis revealed that those three main heavy metal pollutants Cu, Pb and Zn in
      Xihu Scenic Area were from traffic emissions. The purpose of this study was to
      provide basic data and theoretical bases for the ecological risk assessment of
      heavy metals in urban soils and environmental management of urban soils.

PMID- 24946613
TI  - [Distribution and assessment of mercury in the ambient soil of a municipal solid
      waste incinerator].
AB  - The emission of mercury (Hg) from the municipal solid waste incineration has
      inspired widespread attention, especially regarding to the deposition of Hg in
      the surrounding soil, which is issued to be the potential negative factor of
      ambient environment and human health. This study mainly focused on the
      distributions of Hg in the ambient soil of a municipal solid waste incinerator
      located in North China. The pollution of the mercury and its risks to the local
      environment and human health were assessed. Results showed that Hg levels were in
      the range of 0.015-0.25 mg x kg(-1), with an average (0.088 +/- 0.064) mg x kg(
      1). The concentrations of Hg in the soil were obviously influenced by wind
      direction and they were relatively higher in the northwest (downwind) comparing
      with that in the southeast (upwind). The Kriging interpolation method was adopted
      to create a contour map, which intuitively displayed a spatial mercury
      distribution in the soil. The regions with a higher Hg concentration are mainly
      distributed in the north northwest, the north northeast and the west southwest of
      the municipal solid waste incinerator. According to the evaluation results of
      single factor pollution index and geoaccumulation Index, some ambient soil
      samples were polluted by the mercury emission from the municipal solid waste
      incinerator; however, the results of the health risk assessment showed that the
      mercury in the soil had not pose a health hazard to the local population.

PMID- 24946614
TI  - [Phosphorus adsorption characteristics of soils and sediments surrounding Dishui
      Lake in Shanghai].
AB  - Soils and sediments of different origins were collected, which included the
      cropland soils surrounding Dishui Lake, the sediments from rivers, the sediments
      of wetland and the sediments in Dishui Lake. These samples were used for the
      experiment of phosphorus isothermal adsorption. The results of this experiment
      were analyzed and fitted. It shows that, the adsorption-desorption equilibrium
      mass concentration (EPC(0) value) of the sediments in Dishui Lake (0.11-0.63 mg x
      L(-1)) is higher than that of the soils and sediments from other sources, which
      indicates that it is easier to release phosphorus to overlying water. Both the
      Langmuir model and Freundlich model have a high fitting degree to the isothermal
      adsorption of phosphorus. The maximum adsorption capacity (Q(m)) calculated by
      Langmuir model demonstrate that the adsorption capacity of soils and sediments
      from different sources follows the order: sediments from rivers (1 003.05-2977.65
      mg x kg(-1)) > sediments in Dishui Lake (669.77-1 717.94 mg x kg(-1)) > sediments
      of wetland (368.60-1 145.51 mg x kg(-1)) > cropland soils(441.36-702.30 mg x kg(
      ). It shows that the adsorption capacity of cropland soils is the weakest.
      Cropland soils can be a source of phosphorus in Dishui Lake when extra fertilizer
      is used.

PMID- 24946615
TI  - [Impact of SDBS/Na+ on red soil colloidal stability].
AB  - The interactions between soil colloidal-sized particles and organic contaminants
      or inorganic ions profoundly affect numerous soil physical, chemical and
      biological processes. The coupling effect of sodium dodecylbenzene sulfonate
      (SDBS) and Na+ on the aggregation process of red soil colloid was studied using
      the dynamic light scattering method, and the mechanism of interactions between
      soil colloidal-sized particles and SDBS/Na+ was analyzed according to the pH and
      Zeta potential of suspension during the aggregation process. Results show that,
      (1) under a given concentration of Na+, the soil colloidal suspension becomes
      more stable with increasing SDBS concentrations. For example, under 120 mmol x L(
      1) Na+, as the concentrations of SDBS increase from 0 mmol x L(-1) to 10 mmol x
      L(-1), the effective diameters of aggregates decrease from 702 nm to 193 nm, and
      the total average aggregation rates of aggregates decrease from 28.6 nm x min(-1)
      to 3.36 nm x min(-1). (2) Under a given concentration of SDBS, as the
      concentrations of Na+ increase, the Zeta potential of suspension sharply
      decreases, while the effective diameters and the total average aggregation rates
      of aggregates gradually increase. (3) The absolute values of Zeta potential for
      suspensions without adding NaNO3 solution increase from 47.6 mV to 62.2 mV as the
      SDBS concentrations increase, and the pH of the suspensions increase from 6.17 to
      6.76, although these pH values are lower than that of initial soil colloidal
      suspension (6.89). Therefore, the adsorption of SDBS onto soil colloidal-sized
      particles, which is attributed to the hydrophobic effect and electrostatic
      effect, results in the increment of surface charge number, as well as the
      decrease in effective concentration of Na+ around colloidal-sized particles'
      surface (resulting from the steric hindrance of long hydrophobic chain of
      adsorbed SDBS and adsorption of Na+ by SDBS micelle). As a result, soil colloidal
      suspension becomes more stable and needs to absorb more Na+ to aggregate.

PMID- 24946616
TI  - [Effects of stabilization treatment on migration and transformation of heavy
      metals in mineral waste residues].
AB  - Different forms of heavy metals in soil will produce different environmental
      effects, and will directly influence the toxicity, migration and bioavailability
      of heavy metals. This study used lime, fly ash, dried sludge, peanut shells as
      stabilizers in the treatment of heavy metals in mineral waste residues.
      Morphological analyses of heavy metal, leaching experiments, potted plant
      experiments were carried out to analyze the migration and transformation of heavy
      metals. The results showed that after adding stabilizers, the pH of the acidic
      mineral waste residues increased to more than neutral, and the organic matter
      content increased significantly. The main existing forms of As, Pb, and Zn in the
      mineral waste residues were the residual. The contents of exchangeable and
      organic matter-bound As decreased by 65.6% and 87.7% respectively after adding
      fly ash, dried sludge and peanut shells. Adding lime, fly ash and peanut shells
      promoted the transformation of As from the Fe-Mn oxide-bound to the carbonate
      bound, and adding lime and fly ash promoted the transformation of Pb and Zn from
      the exchangeable, Fe-Mn oxide-bound, organic matter-bound to the residual. After
      the early stage of the stabilization treatment, the contents of As, Pb and Zn in
      the leachate had varying degrees of decline, and adding peanut shells could
      reduce the contents of As, Pb and Zn in the leachate further. Among them, the
      content of As decreased most significantly after treatment with fly ash, dried
      sludge and peanut shells, with a decline of 57.4%. After treatment with lime, fly
      ash and peanut shells, the content of Zn decreased most significantly, by 24.9%.
      The addition of stabilizers was advantageous to the germination and growth of
      plants. The combination of fly ash, dried sludge and peanut shell produced the
      best effect, and the Vetiveria zizanioides germination rate reached 76% in the
      treated wasted mineral residues.

PMID- 24946617
TI  - [Study on a new method of fast monitoring toxicity of Cd2+ by algal in water].
AB  - Chlorophyll concentration and photosynthesis activity fluorescence parameters of
      Chlorella pyrenoidosa stressed by different concentrations of Cd2+ were measured
      based on algal growth inhibition tests and photosynthetic activity inhibition
      tests. The relationship between the algal photosynthetic activity inhibition rate
      and 96 h inhibition rate of specific growth rate at different Cd2+ stress times
      was studied by sigmoidal curve fitting and one-way ANOVA analysis. The result
      shows that S function relevance exists between the algal photosynthetic activity
      inhibition rates for 48 h, 53 h, 72 h, 77 h and 96 h respectively and 96 h
      inhibition rate of specific growth rate (R2 > 0.95). Consequently, EC10 (10%
      effective concentration) after 48 h and 53 h inhibition in photosynthetic
      activity inhibition tests could be used to represented EC50 (50% effective
      concentration) in 96 h algal growth inhibition tests for evaluating the Cd2+
      toxicity. Dose-response relationships between the algal photosynthetic activity
      inhibition rates after 48 h and 53 h inhibition and Cd2+ toxic equivalency
      quantity were further analyzed. The method provided a rapid and viable new
      thought to monitoring single Cd2+ toxicity in lab and early warn integrated
      toxicity of pollution in water.

PMID- 24946618
TI  - [Immunosensor for rapid detection of 1,3-dinitrobenzene].
AB  - An immunosensor for the rapid detection of 1,3-dinitrobenzene was developed based
      on an evanescent wave all-fiber biosensing platform with the detection limits of
      0.054 mg x L(-1), and the detection cycle was less than 10 min. Hapten-carrier
      conjugates NB-OVA were synthesized by mixing 4-nitrohippuric acid and OVA
      activated by EDC, and then the conjugates were immobilized onto the silane layer
      on the probe with a heterobifunctional crosslinker. The probe modified had good
      robustness and regeneration performance, which allowed the performance of more
      than 100 assay cycles without significant loss of reactivity. Several water
      samples of different origins were measured with less than 4.5% -10.0% deviation
      of the detection and the recovery rate of 1,3-dinitrobenzene was between 80% and
      120%, which proved the system's precision and accuracy and negligible matrix
      effects. This immunosensor shows great potential in rapid detection of 1,3
      dinitrobenzene in practical waters.

PMID- 24946619
TI  - [Mg/Al layered double hydroxides prepared by microwave-assisted co-precipitation
      method for the removal of bromate].
AB  - In this paper, Mg/Al layered double hydroxides (Mg/Al LDHs) were prepared by the
      microwave-assisted co-precipitation method and the conventional co-precipitation
      method. The samples were labeled as Mg/Al LDHs-MW and Mg/Al LDHs-H, respectively.
      Mg/Al LDHs were characterized by X-ray diffractometer (XRD), Brunauer-Emmett
      Teller (BET), scanning electron microscopy (SEM) and Fourier transform infrared
      (FT-IR). The results showed that the application of microwave in the preparation
      process promoted the formation of smaller pore diameter and higher crystallinity
      particles. The pore size and particle size of Mg/Al LDHs-MW were 41.13 nm and
      427.08 nm, respectively. Batch experiments were investigated to evaluate the
      effect of dosage, initial pH and regeneration frequencies for bromate removal.
      The conclusion showed that the process of bromate removal on Mg/Al LDHs could be
      described by the pseudo-second kinetic model. The Langmuir isotherm well
      described the experimental data, and the Mg/Al LDHs-MW has a stronger adsorption
      capacity while the maximum adsorption capacity (q(0)) of Mg/Al LDHs-MW for
      bromate was 321.26 microg x g(-1) which was larger than the q(0) (288.74 microg x
      g(-1)) of Mg/Al LDHs-H. For the continuous fixed-bed column, model simulations
      using the Thomas model showed that the experimental data obtained at three
      different columns packed with Mg/Al LDHs-MW were able to predict breakthrough
      curves. Simulating the maximum adsorption capacity of adsorption column for
      bromate removal was 288.81 microg x g(-1). When the bed depth was 10 cm, inlet
      concentration was 800 microg x L(-1) and flow rate was 4.0 mL x min, the
      correlation coefficient of model was 0.92, indicating that the experimental data
      was described well by the Thomas model.

PMID- 24946620
TI  - [Discussion on several key points of decision support system for remediation of
      contaminated sites].
AB  - The problem of site contamination has become a focus in the environment
      protection field in the recent years. Decision support system (DSS) for
      remediation of contaminated sites is used for selecting the optimal remediation
      technologies and formulating economic and efficient remediation plans based on
      site investigation and risk assessment. This paper reviewed and analyzed the key
      steps in the decision-making process, including frames, models and methods. In
      addition, the modules and functions of more than 40 types of decision-making
      software in the world were evaluated and summarized. Aimed at the demand of site
      contamination in our country, a skeleton frame and feature were proposed in the
      paper, where the international experience in developed countries has been
      absorbed and learned.

PMID- 24946621
TI  - [A review of multi-scale studies on spatial variation of the lead (Pb)
      concentration in urban soils].
AB  - The accumulation of Pb in urban soils is still apparent in China, and scientific
      assessment and management of risks from Pb-contaminated soils is necessarily
      based on contamination levels and extent evaluated accurately. Lead concentration
      in urban soils has a strong spatial variation and complex spatial structures.
      Carried out in a single spatial scale, most current investigations cannot
      comprehensively reveal characteristics of spatial structures, and did not promote
      more scientific assessment and management of risk. Exploring a new method which
      can help identify the overall spatial structures is needed. To achieve this aim,
      this paper firstly investigated the factors linked to the spatial variability of
      Pb concentration in urban soils, and three major factors were identified: various
      pollution sources, hierarchical pollution processes and heterogeneous urban
      landscape. These factors were form a nested hierarchical spatial structure with
      three spatial levels. Based on the conceptual spatial structure, we proposed a
      method framework guided by geostatistical theory and focused on linear mixed
      model (LMM). This proposed framework can divide the nested hierarchical spatial
      structures of Pb concentration in urban soils into three levels: global trend,
      random variation with spatial autocorrelation, and outliers. Two recommendations
      were given to promote the multiple-scale investigation in spatial variation of
      soil Pb contamination in urban area including: finding more efficient sampling
      strategy and determining the characteristic scale.

PMID- 24946622
TI  - [Review on characteristics and detecting assay of bacterial endotoxin
      contamination in water environment].
AB  - Endotoxins, also known as lipopolysaccharide complexes, are anchored in the outer
      membrane cell wall of most Gram-negative bacteria and some cyanobacteria. They
      are continuously released to environment during cell decay. Being common pyrogens
      and highly immunogenic molecules, endotoxins are related to many human diseases.
      Due to the tolerances and thermo-stability of endotoxin molecules, they were hard
      to be removed by common methods. The health risk caused by the endotoxin
      contamination in drinking water and water environment by various exposure
      pathways have attracted more and more attention in recent years. In this paper,
      the physical and chemical properties, biological activities and detection assay
      of the endotoxin contamination were reviewed, and interfere factors of the main
      assay, the LAL/TAL (Limulus amebocyte lysate/Tachypleus amebocyte lysate) assay,
      for detecting endotoxin in water sample were investigated, and the development
      tendency of the endotoxin detection assay was analyzed.

PMID- 24946623
TI  - [Advances in molecular mechanism of bacterial reduction of hexavalent chromium].
AB  - Cr(VI) has been causing serious environmental pollution due to its
      carcinogenicity, teratogenicity and strong migration. Reduction of Cr( VI) to
      Cr(III), a precipitation that is much less toxic, is an efficient strategy to
      control Cr pollution. Within the strategy, bacterial reduction of Cr(VI) to
      Cr(III) has been considered as one of the best bioremediation methods because of
      its efficiency, environment friendly, and low cost; however, the molecular
      mechanism remains large unknown. This review summarizes Cr(VI) reduction
      bacterial species and its application in pollution control, elaborates the
      pathways of Cr( VI) reduction and functional proteins involved, concludes the
      molecular mechanism of baterial reduction Cr(VI), and discusses the orientation
      of the future research.

PMID- 24946624
TI  - [Anaerobic membrane bioreactors for treating agricultural and food processing
      wastewater at high strength].
AB  - As the second largest amounts of COD discharged in 41 kinds of industrial
      wastewater, it is of great urgency for the agricultural and food processing
      industry to control water pollution and reduce pollutants. Generally the
      agricultural and food processing industrial wastewater with high strength COD of
      8 000-30 000 mg x L(-1), is mainly treated with anaerobic and aerobic processes
      in series, but which exists some issues of long process, difficult maintenance
      and high operational costs. Through coupling anaerobic digestion and membrane
      separation together, anaerobic membrane bioreactor (AnMBR) has typical advantages
      of high COD removal efficiency (92%-99%), high COD organic loading rate [2.3-19.8
      kg x (m3 x d)(-1)], little sludge discharged (SRT > 40 d) and low cost (HRT of 8
      12 h). According to COD composition of high strength industrial wastewater, rate
      limiting step of methanation could be either hydrolysis and acidification or
      methanogenesis. Compared with aerobic membrane bioreactor (MBR), membrane fouling
      of AnMBR is more complicated in characterization and more difficult in control.
      Measures for membrane fouling control of AnMBR are almost the same as those of
      MBR, including cross flow, air sparging and membrane relaxation. For meeting
      discharging standard of food processing wastewater with high strength, AnMBR is a
      promising technology with very short process, by enhancing COD removal
      efficiency, controlling membrane fouling and improving energy recovery.

PMID- 24946625
TI  - [Motor dysfunction in stroke of subacute stage treated with acupuncture: multi
      central randomized controlled study].
AB  - OBJECTIVE: To verify the clinical efficacy of acupuncture on motor dysfunction in
      ischemic stroke of subacute stage. METHODS: The multi-central randomized
      controlled trial was adopted. One hundred and twenty-six cases of ischemic stroke
      of subacute stage were randomized into an acupuncture group (61 cases) and a
      conventional treatment group (65 cases). The basic treatment of western internal
      medicine and rehabilitation training were applied to the patients of the two
      groups. In the acupuncture group, acupuncture was supplemented at the body points
      located on the extensor of the upper limbs and the flexor of the lower limbs. In
      combination, scalp acupuncture was applied to NS5, MS6 and MS6 on the affected
      side. The treatment was given 5 times a week and totally 8 weeks were required.
      The follow-up observation lasted for 3 months. The scores in Fugl-Meyer scale and
      NIHSS scale and Barthel index were compared between the two groups before
      treatment, in 4 and 8 weeks of treatment and the 3-month follow-up observation
      after treatment separately. RESULTS: In 4 and 8 weeks of treatment and the follow
      up observation, Fugl-Meyer scale score was improved obviously in the patients of
      the two groups (all P<0. 01). In 8 weeks of treatment and the follow-up
      observation, Fugl-Meyer scale score in the acupuncture groupwas im proved much
      apparently as compared with that in the conventional treatment group [68. 0 (43.
      0,86. 5) vs 52. 5 (30.3, 77.0), 77.0 (49.5, 89.0) vs 63. 0 (33.0, 84.0), both
      P<0. 05]. Except that NIHSS scale score was not reduced apparently in 4 weeks of
      treatment in the conventional treatment group (P>0.05), the results of NIHSS
      scale at the other time points were all decreased obviously as compared with
      those before treatment in the patients of the two groups (all P<0. 01). In 8
      weeks of treatment and the follow-up observation, the results in the acupuncture
      group were reduced much apparently as compared with those in the conventional
      treatment group [5. 0 (3.0,8.0) vs 7. 0 (3.0,13.8), 4. 0 (1.5,7.0) vs 6.0
      (2.0,11.7) ,both P<0. 05]. In 8 weeks of treatment and the follow-up observation,
      Barthel index was improved obviously as compared with that before treatment in
      the patients of the two groups (all P<0. 05). The improvement in the acupuncture
      group was much more significant as compared with the conventional treatment group
      [75. 0 (60. 0,87. 5) vs 65. O (36. 3, 87. 5), P<0. 051. CONCLUSION: Based on the
      conventional treatment, Acupuncture achieves the satisfactory clinical efficacy
      on motor dysfunction in ischemic stroke of subacute stage.

PMID- 24946626
TI  - [Improvement of survival quality of the patients with hemodialysis treated with
      moxibustion for regulating spleen and stomach functions: multi-central randomized
      controlled study].
AB  - OBJECTIVE: To discuss the impacts of moxibustion for regulating spleen and
      stomach function on the survival quality of the patients of end stage renal
      disease (ESRD) with maintenance hemodialysis (MHD). METHODS: One hundred and nine
      cases of uremia with MHD from 3 hemodialysis centers were randomized into an
      observation group (58 cases) and a control group (51 cases). The regular
      hemodialysis and conventional medication were used in the two groups. In the
      observation group, on the basis of the common treatment, moxibustion was applied
      to Zusanli (ST 36) and Sanyinjiao (SP 6), 2-3 times a day, the treatment of 4
      weeks made one session. Totally, 3 sessions were required and the follow-up
      lasted for 3 months. KDQOL-SF (kidney disease quality of life short form,KDQOL
      SFTM 1. 3) was adopted for the questionnaire investigation on survival quality
      before treatment, after treatment and at the end of follow-up separately in the
      two groups. RESULTS: After treatment, the survival quality scores in terms of
      physical functioning (83.62+/-13.27 vs 79.32+/- 22. 17), general health (58. 88+/
      20.24 vs 48.82+/-20.89) and vitality (77.07+/-15.56 vs 70. 59+/-22.61) in the
      observation group were higher than those in the control group (all P<0. 05). In
      comparison before and after treatment in the same group, the survival quality
      scores in terms of physical functioning, general health, vitality and
      symptoms/problems were all improved in the observation group (all P<0. 05). At
      the end of follow-up, the survival quality scores in terms of physical
      functioning, general health, mental health, social functioning, vitality, effects
      of kidney disease and cognitive function were higher in the observation group as
      compared with those in the control group (all P<0. 05). In comparison of the
      results at the end of follow-up with those before treatment, the survival quality
      scores in terms of vitality, symptoms/problems and cognitive function in the
      observation group were improved (all P< 0. 05). The differences were not
      significant in all of the 19 fields of survival quality evaluation before and
      after treatment, and after follow-up in the control group (all P>0. 05).
      CONCLUSION: Moxibustion for regulating spleen and stomach function improves the
      survival quality of the patients with hemodialysis in terms of physical
      functioning, general health and vitality, which benefits the psychological
      condition of the patients, resulting in the improvements of the survival quality
      in the fields of mental health, social functioning, effects of kidney disease and
      cognitive function.

PMID- 24946627
TI  - [The short-term and long-term effects on neck pain caused by cervical spondylosis
      treated with combination of acupuncture and moxibustion with seed-sized moxa
      cone].
AB  - OBJECTIVE: To evaluate the short-term and long-term effects on treatment of neck
      pain caused by cervical spondylosis with the combination of acupuncture and
      moxibustion with seed-size moxa cone. METHODS: One hundred and forty-five
      patients of neck pain were randomly divided into an acupuncture-moxibustion group
      (49 cases), an acupuncture group (48 cases) and a moxibustion group (48 cases).
      Acupoints of Bailao (Extra), Dazhui (GV 14), Jianzhongshu (SI15) and Zhongzhu (TE
      3) were adopted for all the 3 groups. Acupuncture was applied at all the
      acupoints with 20 min needling retention for the acupuncture group. Moxibustion
      with seed-size moxa cone was used with 5 cones on each point for the moxibustion
      group. And both acupuncture and moxibustion with seed-size moxa cone were adopted
      for the acupuncture-moxibustion group. The treatment was applied once every 3
      days, and 10 treatments should be finished within 4 weeks. Follow-up should be
      carried out for 3 months. The short-term and long-term effects were evaluated
      with the scores of Northwick Park Pain Questionnaire (NPQ) and McGill Pain
      Questionnaire (MPQ) as the indices of therapeutic effect. RESULTS: The NPQ score
      and MPQ score of all the 3 groups after the treating course and the 3-month
      follow-up were both decreased when compared with those before the treatment (all
      P<0. 05). The scores of NPQ and MPQ the acupuncture-moxibustion group were lower
      than that of the other two groups. And the difference had obvious significance
      (P<0. 05). High efficiency of pain relieving for cervical spondylosis could be
      found in all the 3 groups, which showed that short-term and long-term effects
      were good for all the 3 groups. And the highest curative effect could be found in
      acupuncture-moxibustion group. CONCLUSION: Combination of acupuncture and
      moxibustion with seed-size moxa cone has reached a superior effect in short-term
      and long-term for neck pain caused by cervical spondylosis.

PMID- 24946628
TI  - [Efficacy evaluation on knee osteoarthritis treated with acupuncture: non
      randomized concurrent control trial].
AB  - OBJECTIVE: To evaluate the clinical efficacy and efficacy sustainable time of
      acupuncture in knee osteoarthritis (KOA). METHODS: The non-randomized concurrent
      control trial was adopted. One hundred and ninety-three cases of KOA were divided
      into an immediate acupuncture group (group A, 97 cases) and a delayed acupunc
      weeks at the end of treatment. In group B, the same acupuncture therapy was
      applied after waiting 4 weeks. The acupoints in the two groups were Liangqiu (ST
      34), Dubi (ST 35), Zusanli (ST 36), Yanglingquan (GB 34), Yinlingquan (SP 9),
      Xuehai (SP 10), Xiyan (EX-LE 4), Xiyangguan (GB 33). WOMAC (Western Ontario and
      McMasters Universities Osteoarthritis) was used for the assessment of the primary
      index and VAS (visual analogue scale) was for the secondary index. The evaluation
      was accomplished by the patients at the beginning of trial, on the 4th and 8th
      weeks. In each group, 72 patients finished the trial and the data of the lost
      cases were included in the final data analysis. RESULTS: In the 4th week of
      trial, WOMAC score was (25. 8+/-22.0) in group A difference (P<0. 001). VAS
      scorewas (31. 8+/-24. and was (43.8+/-22.2) in group B, indicating the
      significant 6) in group A and was (56. 6 +/-25. 8) in group B, indicating very
      significant difference (P<0. 001). In the 8th week, the efficacy was reduced
      slightly in the follow-up of group A, but it was improved apparently as compared
      Acupuncture relieves joint pain and improves joint function obviously.by th
      patiieffr,a Mtaetfti-?an tf ri-with that before treatment. CONCLUSION:
      Acupuncture relieves joint pain and improves joint function obviously.The effect
      of acupuncture is still sustainable in 4 weeks after terminating the treatment.

PMID- 24946630
TI  - [Clinical observation on focal vitiligo treated with heat-sensitive moxibustion
      in comparison with medication].
AB  - OBJECTIVE: To observe the difference in clinical efficacy on focal vitiligo
      treated with heat-sensitive moxibustion in comparison with medication, and
      discuss its effect mechanism. METHODS: Sixty-eight cases were randomized into a
      moxibustion group (38 cases) and a medication group (30 cases). Additionally, 20
      healthy persons were selected randomly as a normal group. In the moxibustion
      group, the heat-sensitive moxibustion was applied to Hegu(LI 4), Quchi(LI 11),
      Yanglingquan(GB 34), Zusanli(ST 36), Xuehai(SP 10) and the others, once a day. In
      the medication group, triamcinolone acetonide cream was used externally and
      locally, twice a day. In the two groups, the treatment of 15 days made one
      session. The efficacy was observed after continuous treatment for 3 sessions. The
      hemorheology test was done in all of the subjects. The radioimmunoassay was
      adopted to determine the levels of Interleukin 2 (IL-2), Interleukin 6 (IL-6),
      Interleukin 10 (IL-10) and tumor necrosis factor (TNF-alpha) before and after
      treatment. RESULTS: The levels of IL-6, IL-10 and TNF-alpha in vitiligo patients
      were higher significantly than those in the normal group (P<0. 01, P<0. 05), the
      level of IL-2 was lower significantly than that in the normal group (P<0. 01)
      before treatment. After 3 sessions treatment, IL-2 level was increased
      significantly in the moxibustion group and the levels of IL-6, IL-10 and TNF
      alpha were reduced, without significant differences as compared with the normal
      group (all P>0. 05). But the differences were significant as compared with those
      in the medication group (all P<0. 05). The curative and remarkably effective rate
      was 76. 3% (29/38) after treatment in the moxibustion group, which was higher
      significantly than 13. 3% (4/30, P<0. 05) in the medication group. CONCLUSION:
      Heat-sensitive moxibustion achieves very good clinical efficacy on focal
      vitiligo, which is probably via promoting blood circulation and regulating the
      levels of IL-6, IL-10 and TNF-alpha.

PMID- 24946629
TI  - [Clinical observation on common peroneal nerve palsy treated with comprehensive
      therapy].
AB  - OBJECTIVE: To compare the difference of the clinical efficacy on common peroneal
      palsy between the comprehensive therapy of electroacupuncture, moxibustion and
      moving cupping method and western medication. METHODS: Ninety cases of common
      peroneal nerve palsy were randomized into a comprehensive therapy group and a
      western medication group, 45 cases in each one. In the comprehensive therapy
      group, electroacupuncture was applied to Yanglingquan (GB 34), Zusanli (ST 36),
      Xuanzhong (GB 39), Jiexi (ST 41), Taichong (LR 3), Zulinqi (GB 41) and the
      others, combined with warm moxibustion and moving cupping on the lateral side of
      the affected leg. The comprehensive therapy was used once a day. In the western
      medication group, vitamin B1 , 10 mg each time, 3 times a day; and mecobalamine,
      0. 5 mg each time, three times a day were prescribed for oral administration. In
      the two groups, 15 days made one session, and the efficacy was observed after 2
      sessions treatment. RESULTS: The total effective rate of the improvement of
      sensory function and motor nerve function was 97. 8% (44/45) in the comprehensive
      therapy group and was 82. 2% (37/ 45) in the western medication. The efficacy in
      the comprehensive therapy group was better than that of the western medication
      (P<0. 01). The electrophysiological examination showed that the amplitude of
      motor conduction of deep peroneal nerve and that of sensory conduction of
      surficial peroneal nerve after treatment were improved remarkably as compared
      with those before treatment in the comprehensive therapy group (both P<0. 05).
      The amplitude of motor conduction of deep peroneal nerve was improved
      significantly in the comprehensive therapy group as compared with that in the
      western medication group (P<0. 05). CONCLUSION: The comprehensive therapy of
      electroacupuncture, moxibustion and moving cupping method achieves the
      significant efficacy on common peroneal nerve palsy as compared with western
      medication.

PMID- 24946632
TI  - [Case of anal pain caused by lumbar disc herniation].

PMID- 24946631
TI  - [Comparative study on function and surface electromyograpgy in patients of lumbar
      disc herniation treated with acupunctrue and moxibustion].
AB  - OBJECTIVE: To compare the differences in the clinical function and lumbar and
      abdominal myodynamia in patiants of lumbar disc herniation treated with
      moxibustion at Dazhui (GV 14) and Guanyuan (CV 4) and acupuncture. METHODS: Forty
      cases were randomized into a moxibustion group and an acupuncture group, 20 cases
      in each group. In the moxibustion group, the warm moxibustion was applied
      alternatively at Dazhui (GV 14) and Guanyuan (CV 4) once every other day, 1 h
      each time, once every day. In the acupuncture group, acupuncture was applied to
      the corresponding acupoints based on the affected lumbar vertebras, such as Jiaji
      (EX-B 2), Shens-hu (BL 23), Dachangshu (BL 25) and Huantiao (GB 30), etc. , once
      evey day 30 min each time. The treatment for 3 weeks was taken as one session in
      each group. Totally, one session treatment was required. Surface electromyography
      (SEMG) of bilateral paraspinal muscle and rectus muscle, and JOA score of low
      back pain were observed in the two groups. RESULTS: (1) JOA score: the score of
      subjective symptoms, score of activity of daily living (ADL) and total score were
      improved obviously as compared with those before treatment in the two groups
      (P<0.01, P<0.05). The results of subjective symptoms score, score of ADL and
      total score in the acupuncture group were superior to those in the moxibustion
      group after treatment (6.95+/-0.94 vs 5.50 +/-0.89,10. 90+/-1.86 vs 8.90+/- 1.
      92,22.50 +/- 2.82 vs 19.35 +/- 2. 70, all P<0. 05). (2) SEMG comparison: root
      mean-square value (RMS) was all reduced in SEMG of the anteflexion, rear
      protraction, orthostatism, bilateral bending and neck and leg rear flexion for
      strengthening lumbar muscle as compared with those before treatment in the two
      groups (P< 0.05, P<0. 01). RMS of the anteflexion and bilateral bending in the
      acupunture group were reduced much obviously as compared with the moxibustion
      group. In terms of sitting position anteflexion, rear protraction, orthostatism,
      bilateral bending and neck and leg rear flexion for strengthening lumbar muscle,
      median frequency (MF) after treatment was all improved as compared with that
      before treatment in the two groups (P<0. 05, P<0. 01). In terms of anteflexion,
      the electrode MF after treatment was improved much obviously in the acupuncture
      group(P<0. 05). CONCLUSION: Moxibustion at Dazhui (GV 14) and Guanyuan (CV 4) and
      conventional acupuncture all improve muscle function, relieve muscle fatigue,
      increase the ability of anti-muscle fatigue, strengthen lumbar vertebral
      stability, release subjective symptoms and improve ADL. But, the effects of
      moxibustion are slightly lower than those of acupuncture.

PMID- 24946633
TI  - [Clinical observation on two-way quintuple puncture in the treatment of
      ganglion].
AB  - OBJECTIVE: To explore the better therapy in the treatment of ganglion. METHODS:
      Ninety cases of ganglion were randomized into a two-way quintuple puncture group,
      a common quintuple puncture group and a fire needling group, 30 cases in each
      one. In the two-way quintuple puncture group, the "9-in-1" multiple penetrating
      needling technique was used. In the common quintuple puncture group, the
      traditional "5-in-1" multiple penetrating needling technique was applied. In the
      fire needling group, the traditional multiple fire needling technique was
      adopted. The treatment was given once a day, 3 treatments made one session and
      the efficacy was analyzed statistically after 1 session treatment in the three
      groups. RESULTS: All of the three therapeutic methods achieved the efficacy on
      ganglion. The curative rate was 96. 7% (29/30) in the two-way quintuple puncture
      group, which was better obviously than 66.7% (20/30) in the common quintuple
      puncture group and 60. 0% (18/30) in the fire needling group (both P<0. 01).
      CONCLUSION: The two-way quintuple puncture technique achieves the remarkably
      superior efficacy on ganglion as compared with the common quintuple puncture
      technique and fire needling technique.

PMID- 24946634
TI  - [Acupuncture combined with bloodletting and cupping for 23 cases of pathological
      laughing and crying after stroke].

PMID- 24946635
TI  - [Efficacy observation on chronic pelvic pain syndrome of damp-heat stagnation
      pattern treated with acupoint catgut embedding therapy].
AB  - OBJECTIVE: To compare the efficacy difference in the treatment of chronic pelvic
      pain syndrome of Sev-damp-heat stagnation pattern between acupoint catgut
      embedding therapy and western medication. METHODS: enty cases were randomized
      into a catgut embedding group (40 cases) and a western medication group (30
      cases) at the ratio of 4 : 3. In the catgut embedding group, the catgut embedding
      therapy was applied to Sanyinjiao (SP 6), Quchi (LI 11), Huiyin (CV 1), Zusanli
      (ST 36), Zhongji (CV 3), Shenshu (BL 23), etc. The treatment was given once every
      two weeks, the treatment for 4 weeks was as one session and totally 2 sessions
      were required. In the western medication group, tamsulosin hydrochloride capsules
      0. 2 mg, oral administration, once a day, and Indometacin sustained release
      tablets, 75 mg, once a day, 3 tablets each time were prescribed. The symptom
      score of TCM, score of NIH Chronic Prostatitis Symptom Index (NIH-CPSI), lecithin
      body number in prostatic fluid, (SAS) score of Self-Rating Anxiety Scale and
      score of Self-Rating Depression Scale (SDS) were compared before and after
      treatment in the patients of the two groups. The efficacy was evaluated in the
      two groups. RESULTS: (1)The total effective rate was 91. 9% (34/37) in the
      catgutembedding group and was 86. 2% (25/29) in the western medication group. The
      efficacy in the catgutembedding group was better than that in the western
      medication group (P<0. 05). (2) The symptom score of TCM was all reduced
      significantly after treatment in the two groups (both P<0.01), and the result in
      the catgut embedding group was superior to the western medication group (6.42 +/
      2. 81 vs 10. 99+/-3. 11 ,P<0. 01). (3) Lecithin body number was increased
      apparently in the two groups after treatment (both P<0.01), and the result in the
      catgut-embedding group was superior to the western medicine group (33.56+/-5.88
      vs 29. 78+/-7. 06,P<0. 05). (4) Total score of NIH-CPSI, score of pain, score of
      SAS and score of SDS were all improved apparently after treatment in the two
      groups (all P<0. 01), and the results in the catgut embedding group were superior
      to the western medication group (P<0. 01, P<0. 05). CONCLUSION: The acupoint
      catgut embedding therapy achieves the superior efficacy on chronic pelvic pain
      syndrome of damp-heat stagnation pattern as compared with conventional western
      medicine. This therapy relieves clinical symptoms, improves the states of anxiety
      and depression and increases lecithin body number obviously.

PMID- 24946636
TI  - [Observation on therapeutic effect of polycystic ovary syndrome of damp-phlegm
      constitution treated with embedding therapy on back-shu points and front-mu
      points combined with needle-pricking therapy on Sifeng (EX-UE 10)].
AB  - OBJECTIVE: To investigate the effectiveness of polycystic ovary syndrome (PCOS)
      of damp-phlegm constitution treated with embedding therapy on back-shu points and
      front-mu points and needle-pricking therapy on Sifeng (EX-UE 10). METHODS: Eighty
      five patients were randomly divided into 2 groups of observation group (42 cases)
      and control group (43 cases). Embedding therapy on back-shu points and front-mu
      points and needle-pricking therapy on Sifeng (EX-UE 10) were applied to the
      observation group. Points such as Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST
      25), Zhangmen (LR 13), Jingmen (GB 25), Qimen (LR 14), Ganshu (BL 18), Weishu (BL
      21), Pishu (BL 20), Shenshu (BL 23), Dachangshu (BL 25) and Xiaochangshu (BL 27),
      etc. were adopted for embedding therapy. At the same time, needle-pricking
      therapy on Sifeng (EX-UE 10) was also applied once a week. 0. 5 g metformin
      hydrochloride tablet was given to the control group, once a day for the first
      week, and twice a day from the second week. Estimation on therapeutic effect was
      made for both groups after 3 months treatment. Change of symptoms and signs
      scores, fasting insulin (FINS), 2 hour insulin after meal (2hINS) and insulin
      resistance index (HOMA-IR) of both groups before and after treatment were
      observed, and therapeutic effect estimated. RESULTS: The total effective rate of
      the observation group is 97. 6% (41/42), and that of the control group was 95. 4%
      (41/43). There was no significant difference between the two groups (P>0. 05).
      Scores of symptoms and signs after treatment were significantly improved in both
      groups (all P<0. 01), and the observation group was better than the control group
      (7.01+/-4.23 vs 8. 47+/-2. 82,P<0. 05). Compare with those before the treatment,
      FINS, 2hINS and HOMA-IR after the treatment were all decreased in both groups
      (all P<0. 05). The comparison between the two groups showed that differences of
      FIN had no statistic significance (P>0. 05) after the treatment, while both
      differences of 2hINS and HOMA-IR had statistic significance [ 2hlNS: (443. 531+/-
      93. 90) pmol/L vs (621.29+/-93. 87) pmol/L ; HOMA-IR: 4. 88+/-0. 30 vs 5.06+/-0.
      32, both P<0. 05]. The improvement of 2hINS and HOMA-IR in the observation group
      was better than that of the control group. CONCLUSION: Treatment of PCOS of damp
      phlegm constitution with embedding therapy on back-shu points and front-mu points
      and needle-pricking therapy on Sifeng (EX-UE 10) have positive effect, which can
      effectively reduce the insulin resistance, meanwhile, reduce the side-effects of
      western medication.

PMID- 24946637
TI  - [Study on rules of acupoints selection for vertigo in ancient acupuncture].
AB  - The characteristics of selection and matching acupoint and application rules of
      meridians in ancient acupuncture literature for vertigo were explored. The data
      were collected from literature regarding acupuncture for vertigo from the pre-Qin
      period to Qing dynasty and then database was established. Frequency statistics
      method and comparison of support degree were applied to analyze and explore
      application rules of acupoints and meridians, while association rules in data
      mining was used to extract combinations of acupoints. As a result, for treatment
      of vertigo, according to frequency of use and support degree, generally the most
      selected acupoints, in turn, were Fengchi (GB 20), Shangxing (GV 23), Yanggu (SI
      5), Jiexi (ST 41), Zulinqi (GB 41) and Shenting (GV 24), etc.; the most methods
      for matching acupoint were combination of adjacent acupoints, combination of same
      meridian acupoints, combination of the superior-inferior acupoints, combination
      of yang-meridian and yang-meridian acupoints and combination of child-mother
      meridians acupoints; the most selected meridians were bladder meridian of foot
      taiyang, gallbladder meridian of foot-shaoyang and governor vessel. Compared
      between the ancient and modern literature, it was found out that the ancient and
      modern clinic has same points in selection of acupoint-meridian and matching
      acupoints methods. However, the use of Yanggu (SI 5), Jiexi (ST 41) and Feiyang
      (BL 58) as well as combination of child-mother meridians acupoints were less seen
      in modern clinic, which could provide new reference.

PMID- 24946638
TI  - [Cross-sectional survey of characteristics of reaction point Jingtong in balance
      acupuncture].
AB  - OBJECTIVE: To explore the performance patterns of reaction point Jingtong in
      balance acupuncture through multi-center and big-sample clinical investigation.
      Methods The Jingtong points of balance acupuncture on healthy side and affected
      side were observed among 230 cases of cervical spondylosis and scores of self
      discomfort in reaction point, color of skin, changes of skin, morphology of
      subcutaneous tissue and abnormal pressing pain were recorded. The software SPSS
      15.0 was applied to statistically analyze the recorded scores. RESULTS: Among 230
      cases, the reaction point appeared in 226 cases, accounting for 98. 3%. Among the
      226 cases who had reaction point, the total score of symptom and sign was (1.08+/
      1.09) on the healthy side and (0. 84+/-1. 36) on the affected side, which had
      statistical significance (P<0. 01); score of self-discomfort in reaction point
      was (0. 76 +/-0. 83) on the healthy side and (0. 40+/-0.80) on the affected side,
      which had statistical significance (P<0.01); the score of skin color was (0.10+/
      0.36) on the healthy side and (0. 03+/- 0. 19) on the affected side, which had
      statistical significance (P<0. 05); the score of abnormal pressing pain was (2.
      47+/-2. 46) on the healthy side and (1. 39+/-2. 37) on the affected side, which
      had statistical significance (P<0. 01). CONCLUSION: The total score of symptom
      and sign of reaction point Jingtong on the healthy side is higher than that on
      the affected side, indicating positive reaction of Jingtong on the healthy side
      has specificity for cervical spondylosis. When patient has cervical spondylosis
      on either side of neck, the other side will have anomaly in Jingtong.

PMID- 24946639
TI  - [Case of sudden aphonia].

PMID- 24946640
TI  - [Exploration on new role of ancient perilous but key acupoint of renying (ST 9)].
AB  - The specific functions, stimulating methods and ranges of clinical application of
      Renying (ST 9) are explored. Because Renying (ST 9) is located in the neck which
      is a dangerous area, it is perilous if the acupoint is stimulated, so it is
      mostly forbidden in the past dynasties. In recent years, the main stimulating
      methods for Renying (ST 9) include acupuncture and press. The keys of acupuncture
      are to apply correct technique of needle insertion and control the depth and
      direction of needle. The keys of press are focused on strength and time of press.
      Renying (ST 9) is effective for vertigo, palpitation, asthma, hemiplegia,
      aphasia, hysteria, acute attack of pain, hyperplasia of mammary, continuous
      hiccup, disorder of throat and so on. As long as the acupoint location is
      accurate, manipulation is careful and stimulating method is correct, not only the
      safety could be guaranteed, but also the function can be well-played in clinical
      application.

PMID- 24946641
TI  - [Gastroparesis supervened by extensive burns].

PMID- 24946642
TI  - [Fourty-three of chronic tension-type headache treated with oblique needling at
      Taiyang (Ex-HN5)].

PMID- 24946643
TI  - [Protective effect of acupuncture on heart in mice with hyperlipemia and its
      mechanism].
AB  - OBJECTIVE: To observe the inhibiting effect of acupuncture on blood lipid,
      myocardial hypertrophy and fibrosis in mice with hyperlipemia, and explore its
      possible action mechanism. METHODS: Ten inbred mice (C57) were applied. Forty
      ApoE(-/-) mice who removed gene of apolipoprotein E were randomly divided into a
      control group, a non-acupoint group, an acupoint group and a medication group.
      The points 0. 5 cm and 1 cm next to the end of mice tail were respectively
      punctured in the non-acupoint group; "Neiguan" (PC 6) and "Fenglong" (ST 40) were
      punctured in the acupoint group; intragastric administration of simvastatin was
      applied in the medication group. After 8 weeks of treatment, the changes of total
      cholesterol (TC) and ratio of heart to body mass in each group were measured;
      changes of cardiac muscle fiber and ventricular wall thickness were observed;
      enzyme linked immunosorbent assay (ELISA) was used to test the level of
      angiotensin II (Ang I ) in plasma, and western blotting method was used to test
      protein content of angiotensin II type 1 receptor (AT1R) and endothelin-1 type A
      receptor (ETAR) in the heart. RESULTS: After 8 weeks of intervention, compared
      with the control group, rising range of blood lipid was obviously decreased
      (P<0.01) in the acupoint group and medication group, ratio of P<0.01), myocardial
      heart to body mass was decreased (P<0.05), thickness of ventricular wall was
      reduced (P fibrosis was relieved, levels of Ang II and ET-1 in plasma were
      decreased (P<0. 05), content of NO was increased (P<0. 05), and protein content
      of AT1R and ETAR was decreased in the heart (P<0. 05). CONCLUSION: 40) could
      inhibit the rising of blood lipid in ApoE(-/-) mice, lower the levels of Ang II
      and ET-1 in peripheral blood, increase the content of NO and inhibit the
      expression of AT1R and ETAR in heart tissue, which could relieve myocardial
      hypertrophy and fibrosis to play a protective role on heart.

PMID- 24946645
TI  - [Casae of dysphagia caused by stroke].

PMID- 24946644
TI  - [Effects of natural moxibustion on cytokines and specific transcription factors
      in asthma rats].
AB  - OBJECTIVE: To explore the mechanism of natural moxibustion on regulating immune
      imbalance in asthma rats. METHODS: Seventy SD male rats were divided into a
      normal group, a placebo group, a dexamethasone group, a big-cake for long-course
      moxibustion group, a big-cake for short-course moxibustion group, a small-cake
      for long-course moxibustion group and a small-cake for short-course moxibustion
      group, ten rats in each one. The rat model of asthma was established by egg
      albumen sensitization and stimulation in all the groups except the normal group.
      The natural moxibustion was used in all moxibustion groups, in which big cake of
      1 cmX 1 cm size was used in the big-cake groups and small cake of 0.5 cmX 0. 5 cm
      size was used in the small cake groups. According to relevant acupoints, the
      natural moxibustion was performed, 5 h per time, once a day. Four times of
      treatment was considered one course, and three courses were required in the long
      course groups and one course was required in the short-course groups.
      Intraperitoneal injection of dexamethasone was applied in the dexamethasone
      group, which had the same course as long-course moxibustion group. After the
      treatment, changes of EOS in peripheral blood of asthma rats were observed;
      enzyme linked immunosorbent assay (ELISA) was applied to test the contents of
      IgE, IL-4 and IFN-gamma in the lung tissue; real-time Q-PCR method was adopted to
      measure the expression level of transcription factor T-bet and GATA binding
      protein 3 (GATA-3) in the lung tissue. RESULTS: Compared with the normal group,
      the EOS in whole blood as well as IL-4 and IgE in plasma were all increased in
      the placebo group (all P< 0. 01), IFN-gamma in plasma was obviously decreased
      (P<0. 01); while the levels of EOS, IgE and IL-4 were significantly reduced (all
      P<0. 01), the content of IFN-gamma was increased (P<0. 01) in all moxibustion
      groups and dexametnasone group. Compared with the normal group, the expression of
      T-bet mRNA in the placebo group was significantly reduced (P<0. 01). Each
      treatment group could significantly increase the expression of T-bet mRNA and
      reduce that of GATA-3 mRNA (P<0. 01). Compared with the short-course moxibustion
      groups, the expression of T-bet mRNA was obviously increased in the long-course
      moxibustion group and dexamethasone group (both P<0.01), and that of GATA-3 mRNA
      was reduced (P<0.01). There was no significant difference between long-course
      moxibustion group and dexamethasone group (P> 0. 05), and also no significant
      difference could be seen between big-cake moxibustion group and small-cake
      moxibustion group (P>0. 05). CONCLUSION: The natural moxibustion could obviously
      reduce airway inflammation in asthma rats. With time passing, the efficacy is
      enhanced, indicating evident timeliness, which has no apparent relationship with
      the size of moxibustion cake.

PMID- 24946646
TI  - [Effects of assisted-electroacupuncture on recovery of fast tracking anesthesia
      in mPCNL].
AB  - OBJECTIVE: To compare the effects on anesthesia recovery between assisted
      electroacupuncture fast tracking anesthesia and simple fast tracking anesthesia
      in patients with minim ally invasive percutaneous nephrolithotomy (mPCNL).
      METHODS: Eighty cases of mPCNL were selected and randomly divided into a
      treatment group and a control group. Fentanyl (1-2 microg/kg), sevoflurane (8%)
      and rocuronium (0.5 mg/kg) were applied to perform anesthesia induction in both
      groups, and endotracheal inhalation of sevoflurane and intravenous pump injection
      of remifentanil were adopted to main anesthesia status during the operation. 20
      min before anesthesia induction, bilateral Neiguan (PC 6), Neimadian, Hegu (LI
      4), Yangxi (LI 5), Zhongji (CV 3), Qichong (ST 30), Zuwuli (LR 10) were selected
      and punctured in the treatment group, and elecctroacupuncture was given after
      arrival of qi until 30 min after the wake-up from anesthesia and withdrawal of
      endotracheal tube. The dosage for anesthesia maintenance, recovery time of
      awareness, extubation time, incidences of nausea, vomiting and chill and
      irritation of urethral catheters were observed and recorded. RESULTS: (1) The
      dosages of remifentanil and sevoflurane in the treatment group during the
      operation were obviously less than those in the control group [remifentanil: (5.
      27 +/-1.23) micro g/kg h vs (7.35+/-1.70) micro g/kg . h; sevoflurane: (1.12+/
      0.43) vol% vs (2.35+/-0.87) vol% , both P<0. 001]. (2) The recovery time of
      awareness and extubation time in the treatment group were significantly earlier
      than those in the control group [recovery time of awareness: (5.65 +/- 2.34) min
      vs (8. 87 +/- 6. 84) min, P<0. 01; extubation time : (7. 23+/-4. 35) min vs (10.
      62+/-8. 16) min, P<0. 05]. (3) The incidences of nausea, vomiting and chill in
      the treatment group were significantly less than those in the control group (all
      P<0. 05). (4) The irritation of urethral catheters on urethra in the treatment
      group was significantly less than that in the control group (P<0. 001).
      CONCLUSION: The assisted-electroacupuncture anesthesia could reduce the dosage of
      remifentanil and sevoflurane in mPCNL fast tracking anesthesia in urinary
      surgery, reduce the incidences of nausea, vomiting, chill and irritation of
      urethral catheters during recovery stage, and prompt recovery of mPCNL patients.

PMID- 24946647
TI  - [Acupuncture in Oman].
AB  - The status quo and application of acupuncture therapy in Oman is introduced in
      this article. The gene -ral medical condition of Oman is comparatively backward.
      Function of local traditional medicine is limited. Indications of acupuncture in
      Oman are various pain syndromes and motor impairment after stroke. However, it is
      lack of systematic training and management of acupuncture practitioners. And the
      number of acupuncture clinic is comparatively inadequate. Therefore, qualified
      acupuncture training, publicity and cooperation with international organizations
      are highly recommended in the future.

PMID- 24946648
TI  - [The transition of acupuncture and moxibustion in Japan in modern times after
      western medicine spreading to the East].
AB  - The research methods, such as philology of medicine history and comparison
      between tradition and modern and so on were adopted in this article to study the
      acupuncture-moxibustion development after western medicine spreading to the East
      in Japan and its main transition under the impact of western medicine. The
      results showed that from Meiji to Showa period, under the influence of western
      medicine, the transition of Japanese acupuncture-moxibustion mainly embodied in
      following three aspects, incuinng acupuncture works absorbing western medicine
      knowledge, applying experiment measures to explore acupuncture principle and
      launching acupuncture teaching in accordance with Europe and America academy
      educational pattern. The changes on acupuncture works, teaching materials and
      methods of researching and teaching have triggered the transition and
      transformation of Japanese acupuncture-moxibustion from tradition to modern.

PMID- 24946649
TI  - [Analysis of WANG Ji's moxibustion therapy opinion].
AB  - WANG Ji's opinion on moxibustion therapy in Questions and answers of acupuncture
      and moxibustion (Zhenjiu Wendui) was explored and analyzed. With his two
      contraindications of moxibustion as breakthrough points, the arrangement and
      discussion was performed. The results showed that based on summary of moxibustion
      treatment theory before Ming dynasty, WANG Ji could provide characteristic idea,
      which is of great reference value and guide significance to the inheritance and
      development of moxibustion.

PMID- 24946650
TI  - [Bifunctional law in acupuncture theory].
AB  - Taking the basic theory of Chinese medicine as the instruction, through the
      bidirectional features of clinical manifestations, the relative etiology and
      pathology, acupoints and treatments, the bifunctional law in acupuncture theory
      is discussed. And it is held that after the confirmation of bidirectional
      symptoms of some diseases or syndromes, acupoints which have special functions in
      the bifunctional theory of acupuncture with a narrow meaning can be taken as
      major acupoints. And at the same time, other proper acupoints and flexible
      treating methods can be selected under the instruction of the bifunctional law of
      the broad meaning, so as to get the best therapeutic effect.

PMID- 24946651
TI  - [Fifty-two cases of temporomandibular joint dysfunction treated by acupuncture].

PMID- 24946652
TI  - [Treatment of winter diseases in summer].
AB  - To explore the connotation and essence of treatment of winter diseases in summer
      with analysis and deduction. Treating winter diseases in summer is the concrete
      embodiment and application of taking advantage of "recuperating yang in spring
      and summer". Winter diseases are formed by compound factors with deficiency of
      yangqi as the prerequisite and yin as well as cold as the predominant pathogens.
      Its pathological characteristic rests with stagnation in meri-dians and
      collaterals. Aiming at curing chronic diseases, reinforcing yangqi and removing
      stagnation in meridians and collaterals, treatment in summer is a treating
      strategy focused on proper opportunity of treatment, which is expected to yield
      twice the result with half the effort. To select the suitable indications is
      taken as the core of this treating strategy. And at the same time, blind
      expansion without careful consideration is not suggested.

PMID- 24946653
TI  - [Ninety-five cases of perspiration syndrome treated by acupuncture on acupoint
      group of enriching qi and yin].

PMID- 24946654
TI  - [Warm acupuncture combined with muscle strength technique for 46 cases of
      piriformis syndrome]].

PMID- 24946655
TI  - [CHENG DAN-AN's contribution to direct moxibustion with moxa cone in Chinese
      Acupuncture and Moxibustion].
AB  - In the book of Chinese Acupuncture and Moxibustion by CHENG Dan-an, direct
      moxibustion with moxa cone was regarded as a classic style of moxibustion because
      of its innate character of heat induced thermal stimulus and burn toxin. CHENG
      Dan-an made the quantity of moxibustion more controllable through the selection
      of moxa wool, the size and number of moxa cones, and the tightness of moxa cones,
      etc. CHENG Dan-an 's clinical experience is summarized through treating stubborn
      and infectious diseases with direct moxibustion with moxa cone. The results
      showed that only with understanding the characteristics of moxibustion and key
      pathological mechanism of suitable disease could direct moxibustion with moxa
      cone and the appropriate methods be performed correctly. CHENG Dan-an confirmed
      the clinical effect of treating stubborn and intectious diseases with direct
      contact moxibustion with moxa cone, and optimized the specific operation scheme
      of direct moxibustion with moxa cone. It tell us that we should deeply study on
      moxibustion, to make it wide spread in the hereafter, bring benefit to mankind.

PMID- 24946656
TI  - [Remarks on the relationship between deqi and effect of acupuncture].
AB  - Acupuncturists have always paid high attention to deqi (needling sensation) in
      clinical. However, relationship between deqi and curative effect has not been
      elucidated yet. In order to have a further understanding on effect of deqi on
      clinical effect, through study on literature associated with deqi since the
      establishment of People's Republic of China in 1949, it is held that various
      factors can influence therapeutic effect of acupuncture treatment, including
      whether needling sensation appears or not, the speed of deqi, the intensity of
      deqi, different types of sensations as well as propagated sensation along
      meridians (PSM). Joint launched multidisciplinary researches should be carried
      out to reveal the influence principle of deqi on acupuncture effect, and to lay
      foundations for the further studies on mechanism of deqi.

PMID- 24946657
TI  - Negative pressure and muscle activity during discrete sips from high resistance
      straws.
AB  - The purpose of the current investigation was to explore how intra-oral negative
      pressure and submental muscle activity vary across sips from straws varying in
      internal diameter and across conditions of low versus high effort. Healthy adults
      took discrete sips from four straws varying in internal diameter. Sips were
      performed under normal and high effort conditions. Submental surface
      electromyography (sEMG) and negative intra-oral pressure were recorded during
      sips. Significant main effects of straw condition were observed for negative
      intra-oral pressure. A non-significant trend for increased muscle activity
      associated with smaller straw diameter was also observed. Significant main
      effects of effort condition were observed for both submental sEMG and negative
      intra-oral pressure. The findings are interpreted as supporting the clinical
      hypothesis that high resistance drinking straws varying in diameter may offer
      systematic overload to the oral musculature. The findings also support
      encouraging maximum effort to achieve even further overload.

PMID- 24946658
TI  - Effects of body position and sex group on tongue pressure generation.
AB  - Fine control of orofacial musculature is necessary to precisely accelerate and
      decelerate the articulators across exact distances for functional speech and
      coordinated swallows (Amerman & Parnell, 1990; Benjamin, 1997; Kent, Duffy,
      Slama, Kent, & Clift, 2001). Enhanced understanding of neural control for such
      movements could clarify the nature of and potential remediation for some
      dysarthrias and other orofacial myofunctional impairments. Numerous studies have
      measured orolingual force and accuracy during speech and nonspeech tasks, but
      have focused on young adults, maximum linguapalatal pressures, and upright
      positioning (O'Day, Frank, Montgomery, Nichols, & McDade, 2005; Solomon & Munson,
      2004; Somodi, Robin, & Luschei, 1995; Youmans, Youmans, & Stierwalt, 2009).
      Patients' medical conditions or testing procedures such as concurrent
      neuroimaging may preclude fully upright positioning during oral motor assessments
      in some cases. Since judgments about lingual strength and coordination can
      influence clinical decisions regarding the functionality of swallowing and
      speech, it is imperative to understand any effects of body positioning
      differences. In addition, sex differences in the control of such tasks are not
      well defined. Therefore, this study evaluated whether pressures exerted during
      tongue movements differ in upright vs. supine body position in healthy middle
      aged men and women. Twenty healthy middle-aged adults compressed small air-filled
      plastic bulbs in the oral cavity at predetermined fractions of task-specific peak
      pressure in a randomized block design. Tasks including phoneme repetitions and
      nonspeech isometric contractions were executed in upright and supine positions.
      Participants received continuous visual feedback regarding targets and actual
      exerted pressures. Analyses compared average pressure values for each subject,
      task, position, and effort level. Speech-like and nonspeech tongue pressures did
      not differ significantly across body position or sex groups. Pressure matching
      was significantly less accurate at higher percentages of maximum pressure for
      both tasks. These results provide preliminary comparative data for the clinical
      assessment of individuals with orofacial myofunctional and neurological
      disorders.

PMID- 24946659
TI  - Mandibular angle and coronoid process fracture secondary to orofacial dystonia:
      report of a case.
AB  - As the angle is a weak region in the continuity of mandible, so it is more prone
      to fracture. It has been proven time and again that coronoid fracture results
      from a strong sudden contraction of temporalis. Muscular forces influence the
      remodeling of bones. Orofacial dystonia is a centrally mediated disease in which
      there is an uncontrolled spasmodic contraction of facial and masticatory muscles.
      This continuous force applied over a long period of time has the potential to
      unfavorably remodel or weaken bone. A case is presented in which the dystonic
      action of facial musculature gradually resorbed the bone to such an extent that
      there was spontaneous fracture at the right angle of mandible as well as the
      contra lateral coronoid. Management of this fracture posed a challenge at every
      step eventually leading to resection of the ramus-condyle unit. No case has been
      reported so far in the literature where dystonic movements have resulted in
      fracture of the mandible.

PMID- 24946660
TI  - Electropalatography as an adjunct to nonspeech orofacial myofunctional disorder
      assessments: a feasibility study.
AB  - The purpose of this study was to determine if electropalatography (EPG) would be
      a useful adjunct and feasible option for those conducting clinical assessments of
      individuals with suspected nonspeech orofacial myofunctional disorders (NSOMD).
      Three females (two adults, one child) were referred by their orthodontist for
      assessment of suspected NSOMD. Three adults and one child without NSOMD were
      recruited for the purpose of evaluating methodological construct, and to provide
      comparisons for participants with NSOMD. Using EPG, lingual-palatal timing and
      contact patterns of 105 saliva swallows (45 with NSOMD, 60 without NSOMD) were
      analyzed by compartmentalizing the sensor display and tracking the order and
      duration of activation. Lingual-palatal contact patterns were compared in terms
      of four stages: prepropulsion, propulsion, postpropulsion, release. Coding the
      lingual-palatal activation in an operationalized manner was a valuable adjunct
      for describing lingual-palatal timing and contact patterns. Participants with
      NSOMD showed unique lingual-palatal contact patterns that differed from the
      patterns of the participants without NSOMD, and from each other. EPG is a
      potential adjunct to the non-instrumental assessment of NSOMD. Larger scale
      investigations using EPG should proceed.

PMID- 24946661
TI  - Case history: improved maxillary growth and development following digit sucking
      elimination and orofacial myofunctional therapy.
AB  - Orofacial myologists are frequently called upon to address retained oral habit
      concerns. During this process, current I.A.O.M. recommended treatment includes
      addressing tongue, lip, and jaw rest posture concerns. Following digit sucking
      remediation, we may also be called upon to address these rest posture issues, and
      tongue thrust more aggressively together. In this process, facial growth and
      development and jaw structure may coincidentally improve as a result of 'nature
      taking its course' by addressing both swallow AND rest posture. In a select
      subset of clients, dramatic improvements may occur if the timing is right. This
      article discusses one such case that appears to have yielded a significant
      improvement in oral postures influencing improved facial and oral growth and
      development.

PMID- 24946663
TI  - Cephalometric evaluation of the airway space and head posture in children with
      normal and atypical deglutition: correlations study.
AB  - Head posture has been related to pharyngeal space, especially in the syndrome of
      obstructive sleep apnea (OSA) in adults. However no studies were found that
      evaluated the possible correlation between head posture and pharyngeal airway
      space measured in children with atypical swallowing. The purpose of this study
      was to evaluate the possible correction between head posture and the measurement
      of pharyngeal space on radiographs of children who were in the period of mixed
      dentition who demonstrated atypical swallowing and in children with normal
      deglutition. A retrospective clinical study, using cephalometric analysis of
      lateral radiographs to obtain measures of the antero-posterior dimension of the
      pharyngeal airway space (PAS) and the angle formed between the base of the skull
      and the odontoid process (CC1) between two groups: the 55 radiographs
      experimental group (with atypical swallowing) and 55 radiographs of the control
      group (normal swallowing). The Spearman Coefficient of Correlation was used to
      evaluate the possible relationship between PAS and CC1 was used. Results
      indicated a positive correlation between measures of CC1 and PAS (r = 0357) only
      in the control group (normal swallowing). CONCLUSIONS: There is positive
      correlation between head posture and measure pharyngeal airway space (PAS) in the
      group of normal swallowing. This correlation was not observed in the experimental
      group (atypical swallowing).

PMID- 24946662
TI  - Videofluoroscopy of the oral phase of swallowing in eight to twelve years old
      children with dental malocclusion.
AB  - The objective of this study was to describe the oral phase of swallowing in
      individuals with dental malocclusion and to generate data that would contribute
      to the rehabilitation of those patients. The study was based on the evaluation of
      the swallowing system through videofluoroscopy on thirty-four children of both
      genders, aged eight to twelve years old who present with Angle Class II and III
      dental malocclusions. Thirteen children of similar age and gender presenting
      normal dental occlusion formed the control group. The results indicated that the
      oral phase of swallowing is different between individuals with normal occlusion
      and malocclusion. Dental occlusion types Angle Class II and III did not present a
      swallowing pattern, independently of the amount of liquid ingested. The
      swallowing appeared effective in the oral phase of individuals with dental
      malocclusion, even though adaptations were identified. The outcome, in the
      absence of a single pattern and the efficiency of the adapted swallowing
      demonstrates, first a need for additional research investigating orofacial
      myofunctional treatment for patients with malocclusion and second how such
      analyses should focus on contributing positively to the rehabilitation of these
      patients.

PMID- 24946664
TI  - Looking forward. ACA revenue sources and trends.

PMID- 24946665
TI  - The SGR repeal: bad politics ruined sound policy.

PMID- 24946666
TI  - World innovation summit for health provides a global perspective on surgery.

PMID- 24946667
TI  - Teaching the teacher: An ethical model for international surgical missions.
AB  - Concerns linger about how to provide equitable global health care and how to
      address the great unmet health care needs in many countries. The burden of
      outreach mostly falls on universities. Universities and educational institutions
      by design are capable of defining the necessary directions for change. The
      challenge for universities participating in global health care and education is
      creating and sustaining robust health systems tailored to each community by
      evaluating the existing system and taking note of stakeholders, opinion leaders,
      and the availability of sustained resources in the milieu of the rapidly changing
      global health care structures.4 The model described here is rooted in educational
      theory and based on the belief that sharing surgical knowledge is the most
      effective way to improve access to necessary care for underserved patient
      populations. Positive changes can be made by developing relationships among
      health care personnel and new approaches to educational problems. This positive
      outcome was largely due to the development of new attitudes by professionals and
      their approach to education and collaboration. Development of a systemic approach
      to global health care problems is a daunting task. The solution is neither simple
      nor easy, and the active participation of the assisted party is highly
      encouraged. *

PMID- 24946668
TI  - And the beat goes on: surgeons take a break from the OR to play in rock bands.

PMID- 24946669
TI  - Avoiding the 2015 medicare EHR incentive program penalty.

PMID- 24946670
TI  - Neoadjuvant cancer therapy: benefitting patients and improving cancer care.

PMID- 24946671
TI  - National time out day focuses on every patient, every time.

PMID- 24946672
TI  - NTDB data points: flotation devices -- Mae West style.

PMID- 24946674
TI  - In memoriam: Frank T. Padberg, Sr., MD, FACS: ACS department director, DSA
      recipient, and trailblazer in neurosurgery.

PMID- 24946673
TI  - 2014 leadership program. Emotional intelligence, mentoring are keys to effective
      performance.

PMID- 24946680
TI  - Abstracts of the Australian and New Zealand Society for Geriatric Medicine Annual
      Scientific Meeting, 28-30 May 2014, Melbourne, VIC, Australia.

PMID- 24946675
TI  - The development and evolution of family therapy research: its impact on practice,
      current status, and future directions.
AB  - Science has always been a central part of family therapy. Research by early
      pioneers focused on studying the efficacy of both couple and family interventions
      from a systemic perspective. Today we know more now than ever before about the
      processes of diverse families and the therapeutic outcomes of family therapy
      practices. Despite the acknowledged importance of family therapy research, there
      are still questions about its impact on "real life" practice. Despite all the
      flaws of each, research and practice are critical interacting elements of a
      dialectic relationship: High-quality practice combines reliable scientific
      knowledge with individual clinical judgment made by family therapists in the
      context of their dynamic transactions with a family or couple. Future research
      can help uncover the mechanisms we have yet to know and test the ones we have
      identified while the dynamic interaction of research and practice that can lead
      to further innovations and developments central to the future of family therapy. 

PMID- 24946681
TI  - Authorship in facilitated communication: an analysis of 11 cases.
AB  - We studied the authorship of messages produced through facilitated communication
      (FC) for all users of FC in two comprehensive schools in a small city in Finland.
      The participants were 11 children with intellectual disabilities, including
      autism, all having used FC from 1-3 years. The test conditions involved open and
      blind information-passing tasks in which the participants were directed to write
      down the contents of written or pictorial stimuli. The results failed to validate
      FC as a method of communication for any participant or facilitator. An analysis
      of the messages produced under the FC condition revealed a large degree of
      facilitator influence on the content of the messages produced. Additionally, FC
      impaired the performance of the two participants who had previously demonstrated
      some independent writing skills.

PMID- 24946682
TI  - Array-on-a-disk? How Blu-ray technology can be applied to molecular diagnostics.
AB  - This editorial comments on the balance and perspectives of compact disk
      technology applied to molecular diagnostics. The development of sensitive, rapid
      and multiplex assays using Blu-ray technology for the determination of
      biomarkers, drug allergens, pathogens and detection of infections would have a
      direct impact on diagnostics. Effective tests for use in clinical, environmental
      and food applications require versatile and low-cost platforms as well as cost
      effective detectors. Blu-ray technology accomplishes those requirements and
      advances on the concept of high density arrays for massive screening to achieve
      the demands of point of care or in situ analysis. 

PMID- 24946683
TI  - Impact of dental anxiety and fear on dental care use in Brazilian women.
AB  - OBJECTIVES: This study investigated the relationship between dental anxiety and
      fear, demographic and socioeconomic characteristics, and dental attendance
      patterns in a sample of women in Brazil. METHODS: A cross-sectional study of
      women in healthcare centers was conducted during an immunization campaign in the
      city of Pelotas in southern Brazil. Interviews were conducted to assess dental
      anxiety and fear, education level, family income, marital status, and the use of
      dental services. Data were analyzed by Poisson regression models, with estimation
      of the prevalence ratio and the rate ratio (RR). RESULTS: A total of 608 women
      aged 16-50 years (mean age 29.3 +/- 7.2 years) were included in the study. Dental
      anxiety and fear scores (according to Corah's Dental Anxiety Scale) ranged from 4
      to 20. Of the 608 participants, 59.5 percent displayed low dental fear, 18.1
      percent had moderate dental fear, and 22.4 percent displayed high dental fear. A
      total of 60.2 percent of the women exhibited irregular dental attendance
      patterns, characterized by never visiting a dentist, or only visiting when
      experiencing pain. After adjustments, the presence of at least moderate dental
      anxiety and fear was associated with low education levels (RR 1.43; 95 percent CI
      1.11-1.84), low family income (RR 1.33; 95 percent CI 1.06-1.68), and irregular
      dental attendance patterns (RR 1.83; 95 percent CI 1.41-2.37). CONCLUSIONS: In
      this sample of Brazilian women, dental anxiety and fear were strongly associated
      with socioeconomic characteristics and dental attendance patterns.

PMID- 24946684
TI  - Neutralization of chemokine-like factor 1, a novel C-C chemokine, protects
      against focal cerebral ischemia by inhibiting neutrophil infiltration via MAPK
      pathways in rats.
AB  - BACKGROUND: Inflammation plays a key role in the pathophysiology of ischemic
      stroke. Some proinflammatory mediators, such as cytokines and chemokines, are
      produced in stroke. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine,
      displays chemotactic activities in a wide spectrum of leukocytes and plays an
      important role in brain development. In previous studies, we have found that the
      expression of CKLF1 increased in rats after focal cerebral ischemia and treatment
      with the CKLF1 antagonist C19 peptide decreased the infarct size and water
      content. However, the role of CKLF1 in stroke is still unclear. The objective of
      the present study was to ascertain the possible roles and mechanism of CKLF1 in
      ischemic brain injury by applying anti-CKLF1 antibody. METHODS: Male Sprague
      Dawley rats were subjected to one-hour middle cerebral artery occlusion. Antibody
      to CKLF1 was applied to the right cerebral ventricle immediately after
      reperfusion; infarct volume and neurological score were measured at 24 and 72
      hours after cerebral ischemia. RT-PCR, Western blotting and ELISA were utilized
      to characterize the expression of adhesion molecules, inflammatory factors and
      MAPK signal pathways. Immunohistochemical staining and myeloperoxidase activity
      was used to determine the extent of neutrophil infiltration. RESULTS: Treatment
      with anti-CKLF1 antibody significantly decreased neurological score and infarct
      volume in a dose-dependent manner at 24 and 72 hours after cerebral ischemia.
      Administration with anti-CKLF1 antibody lowered the level of inflammatory factors
      TNF-alpha, IL-1beta, MIP-2 and IL-8, the expression of adhesion molecules ICAM-1
      and VCAM-1 in a dose-dependent manner. The results of immunohistochemical
      staining and detection of MPO activity indicated that anti-CKLF1 antibody
      inhibited neutrophil infiltration. Further studies suggested MAPK pathways
      associated with neutrophil infiltration in cerebral ischemia. CONCLUSIONS:
      Selective inhibition of CKLF1 activity significantly protects against
      ischemia/reperfusion injury by decreasing production of inflammatory mediators
      and expression of adhesion molecules, thereby reducing neutrophils recruitment to
      the ischemic area, possibly via inhibiting MAPK pathways. Therefore, CKLF1 may be
      a novel target for the treatment of stroke.

PMID- 24946685
TI  - The ears of the African elephant: unexpected high seroprevalence of Plasmodium
      ovale and Plasmodium malariae in healthy populations in Western Africa.
AB  - BACKGROUND: Malaria Is A Life-Threatening Pathology In Africa. Plasmodium
      Falciparum And Plasmodium Vivax Attract The Most Focus Because Of Their High
      Prevalence And Mortality. Knowledge About The Prevalence Of The Cryptic Pathogens
      Plasmodium Ovale And Plasmodium Malariae Is Limited. Thanks To Recombinant Tools,
      Their Seroprevalence Was Measured For The First Time, As Well As The Prevalence
      Of Mixed Infections In A Malaria-Asymptomatic Population In Benin, A Malaria
      Endemic Country. METHODS: A Panel Of 1,235 Blood Donations Collected Over Ten
      Months In Benin Was Used For Validation Of The Recombinant Tools. Recombinant P.
      Falciparum, P. Malariae, P. Ovale MSP1, And P. Falciparum AMA1 Were Engineered
      And Validated On A Biobank With Malaria-Infected Patients (N = 144) Using A
      Species-Speific ELISA Test (Recelisa). Results Were Compared To An ELISA Using A
      Native P. Falciparum Antigen (NatELISA). RESULTS: Among Microscopically Negative
      African Blood Donors, 85% (1,050/1,235) Present Antibodies Directed To Native P.
      Falciparum, 94.4% (1,166/1,235) To rPfMSP1 And rPfAMA1, 56.8% (702/1,235) To
      rPoMSP1, 67.5% (834/1235) To rPmMSP1 And 45.3% Of The Malaria Seropositive
      Population Had Antibodies Recognizing The Three Species. CONCLUSION: A High Rate
      Of Antibodies Against P. Ovale And P. Malariae Was Found In Asymptomatic Blood
      Donors. The Proportion Of Mixed Infections Involving Three Species Was Also
      Unexpected. These Data Suggest That Determining Seroprevalence For These Cryptic
      Species Is An Appropriate Tool To Estimate Their Incidence, At The Eve Of
      Upcoming Anti-P. Falciparum Vaccination Campaigns.

PMID- 24946686
TI  - Plant pattern-recognition receptors.
AB  - Plants are constantly exposed to would-be pathogens in their immediate
      environment. Yet, despite relying on innate immunity only, plants are resistant
      to most microbes. They employ pattern-recognition receptors (PRRs) for sensitive
      and rapid detection of the potential danger caused by microbes and pests. Plant
      PRRs are either surface-localized receptor kinases (RKs) or receptor-like
      proteins (RLPs) containing various ligand-binding ectodomains that perceive
      pathogen-associated molecular patterns (PAMPs) or damage-associated molecular
      patterns (DAMPs). In this review, I summarize our current knowledge of plant PRRs
      and their ligands, illustrating the multiple molecular strategies employed by
      plant PRRs to activate innate immune signaling to survive. 

PMID- 24946687
TI  - Silencing BMP-2 expression inhibits A549 and H460 cell proliferation and
      migration.
AB  - BACKGROUND: Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-beta
      superfamily that is closely correlated with many malignancies, particularly lung
      cancer. However, the effects of silenced BMP-2 on lung cancer cell proliferation
      and migration are not clear. METHODS: Using quantitative real-time RT-PCR, BMP-2
      mRNA expression was detected in 61 non-small cell lung cancer (NSCLC) samples.
      Survival curves were generated using follow-up data. Relationships between
      clinical or pathological characteristics and prognosis were analyzed. Cell
      viability assays and transwell migration assays were used to evaluate the effects
      of BMP-2 silencing on cell proliferation and migration of A549 and H460 cells.
      RESULTS: BMP-2 mRNA expression was higher in NSCLC tissues compared to matched
      adjacent normal tissues (P<0.01). High BMP-2 expression levels were significantly
      associated with the occurrence of lymph node metastases and tumor stage (P<0.05).
      There were significant differences in survival curves between groups with
      metastatic lymph nodes and non-metastatic lymph nodes, as well as between groups
      with low BMP-2 expression and groups with high BMP-2 expression. In addition, we
      observed decreased proliferation and migration rates of the NSCLC-derived cell
      lines A549 and H460 that were transfected with siBMP-2 (P<0.05). CONCLUSION: BMP
      2 mRNA is overexpressed in NSCLC samples and is a risk factor for survival in
      patients with NSCLC. BMP-2 silencing can significantly inhibit A549 and H460 cell
      proliferation and migration. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4263254471298866.

PMID- 24946688
TI  - Long-term prognosis of clinically early IgA nephropathy is not always favorable.
AB  - BACKGROUND: The long-term prognosis of clinically early IgA nephropathy (IgAN)
      patients remains to be clarified. We investigated the long-term outcomes of IgAN
      patients with an apparently benign presentation and evaluated prognostic factors
      for renal survival. METHODS: We included patients with biopsy-proven IgAN who had
      estimated glomerular filtration rates (eGFR) >= 60 mL/min/1.73 m2, normal blood
      pressure, and proteinuria <0.5 g/day at the time of biopsy. The primary outcome
      was progression to end-stage renal disease (ESRD). The secondary outcome was a
      50% increase in serum creatinine level or an increase in proteinuria to >1 g/day.
      RESULTS: The analysis included 153 patients who met the inclusion criteria. At
      diagnosis, their median systolic blood pressure was 120 (110-130) mmHg, eGFR was
      85.9 (74.9-100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13-0.38) g/day. Of
      these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was
      85.5%. Three patients had increased serum creatinine levels and 11 developed
      proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe
      degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence
      interval [CI] 1.44-24.45, P=0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI
      1.20-31.79, P=0.029) were independent predictors of the secondary outcome.
      CONCLUSIONS: This study showed that the prognosis of early IgAN was not always
      favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia
      and interstitial fibrosis should also be considered important prognostic factors
      in clinically early IgAN patients.

PMID- 24946689
TI  - Lack of replication of higher genetic risk load in men than in women with
      systemic lupus erythematosus.
AB  - INTRODUCTION: We aimed to replicate a recent study which showed higher genetic
      risk load at 15 loci in men than in women with systemic lupus erythematosus
      (SLE). This difference was very significant, and it was interpreted as indicating
      that men require more genetic susceptibility than women to develop SLE. METHODS:
      Nineteen SLE-associated loci (thirteen of which are shared with the previous
      study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European
      ancestry. Genetic risk load was calculated as sex-specific sum genetic risk
      scores (GRS(s)). RESULTS: Our results did not replicate those of the previous
      study at either the level of individual loci or the global level of GRS(s).
      GRS(s) were larger in women than in men (4.20 +/- 1.07 in women vs. 3.27 +/- 0.98
      in men). This very significant difference (P < 10(-16)) was more dependent on the
      six new loci not included in the previous study (59% of the difference) than on
      the thirteen loci that are shared (the remaining 41%). However, the 13 shared
      loci also showed a higher genetic risk load in women than in men in our study (P
      = 6.6 * 10(-7)), suggesting that heterogeneity of participants, in addition to
      different loci, contributed to the opposite results. CONCLUSION: Our results show
      the lack of a clear trend toward higher genetic risk in one of the sexes for the
      analyzed SLE loci. They also highlight several limitations of assessments of
      genetic risk load, including the possibility of ascertainment bias with loci
      discovered in studies that have included mainly women.

PMID- 24946691
TI  - Long-term ongoing pregnancy rate and mode of conception after a positive and
      negative post-coital test.
AB  - OBJECTIVE: Many fertility clinics have decided to abolish the post-coital test.
      Yet, it is a significant factor in prognostic models that predict the spontaneous
      pregnancy rate within one year. The aim of this study was to evaluate (1) the
      long-term outcome of infertile couples with a positive or a negative post-coital
      test during their fertility work-up and (2) the contribution of the different
      modes of conception. DESIGN: Retrospective cohort study. SETTING: Three fertility
      clinics in the Netherlands, of which two are secondary care training hospitals
      and is a one tertiary care academic training hospital. POPULATION: 2476 newly
      referred infertile couples, where a post-coital test was performed in 1624
      couples. METHODS: After basic fertility work-up, couples were treated according
      to the national treatment protocols. MAIN OUTCOME MEASURES: Spontaneous and
      overall ongoing pregnancy rate. RESULTS: The spontaneous and overall ongoing
      pregnancy rates after three years were 37.7 and 77.5% after a positive post
      coital test compared with 26.9 and 68.8% after a negative test (p < 0.001). Even
      in couples with severe male factor infertility (total motile sperm count <3) (p =
      0.005) and mild male factor infertility (total motile sperm count 3-20) (p <
      0.001), there was a significantly higher spontaneous ongoing pregnancy rate,
      justifying expectant management. CONCLUSION: After a follow-up of three years a
      positive post-coital test is still associated with a higher spontaneous and a
      higher overall ongoing pregnancy rate, even in couples with severe male factor
      infertility.

PMID- 24946690
TI  - Reduced plasma levels of soluble interleukin-7 receptor during graft-versus-host
      disease (GVHD) in children and adults.
AB  - BACKGROUND: Interleukin 7 (IL-7) signals via the IL-7 receptor (IL-7R) and drives
      homeostatic T-cell proliferation in patients after allogeneic hematopoietic stem
      cell transplantation (aHSCT). PURPOSE: We performed a prospective study in adults
      (n = 33) and children (n = 29) undergoing aHSCT measuring plasma IL-7 and soluble
      IL-7R (sIL-7R) concentrations between 1 and 12 months after HSCT in order to
      investigate the link between sIL-7R and clinical events after aHSCT. RESULTS: sIL
      7R, but not IL-7, increased with time after HSCT in plasma from all patients
      enrolled in the study. sIL-7R values were higher at 2, 3, and 6 months (p < 0.01)
      if the donor was a sibling as compared to an unrelated donor. Increased sIL-7R
      levels were also identified in plasma from patients who were not treated with
      anti-thymocyte globulin (ATG). Low sIL-7R was associated with any grade of acute
      graft-versus-host disease (GVHD) at 2 and 6 months (p = 0.02) and with a positive
      CMV PCR at 2 months after HSCT (p < 0.05). Patients with cytomegalovirus (CMV)
      reactivation had increased IL-7 values at 2 and 3 months (p = 0.02) after HSCT.
      In multivariate analysis, lower sIL-7R levels were associated with acute GVHD
      (relative hazard (RH): 0.70, p > 0.01) and sibling donors (RH: 2.23, p = 0.004).
      Recipients of sibling grafts showed high levels of IL-7 (RH: 1.38, p < 0.05) and
      bone marrow recipients had low IL-7 levels (RH: 0.73, p = 0.04). CONCLUSIONS:
      Measurement of the sIL-7R/IL-7 axis will help in guided immune monitoring after
      HSCT and guided interference with sIL-7R may be explored in GVHD management.

PMID- 24946692
TI  - Even mild cases of paediatric Henoch-Schonlein purpura nephritis show significant
      long-term proteinuria.
AB  - AIM: Henoch-Schonlein purpura (HSP) is a common cause of paediatric renal disease
      in children, representing 10-15% of paediatric glomerulonephritis. This study
      examined the long-term outcome of biopsy-proven HSP nephritis to identify
      correlations between disease development and treatment. METHODS: Patients from
      three French centres were retrospectively analysed. RESULTS: We followed up 142
      patients aged from 2 to 10.5 years with HSP nephritis, graded according to the
      International Study Group of Kidney Disease in Childhood classification. Mean (+/
      SD) age at presentation was 7.6 +/- 2.8 years. Nephrotic range proteinuria was
      present in 28% of patients with Grade II lesions, 60% with Grade III and 90% with
      Grade IV. Significant proteinuria (>0.5 g/L) was found in nine of 48 patients 3
      years after renal biopsy, eight of 25 patients after 5 years and three of 14
      patients after 10 years. There was no correlation between the proteinuria risk at
      3, 5 or 10 years and the initial histological lesion or treatment modality.
      Treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor
      blockers (ACEi/ARB) was linked to lower proteinuria, especially if it was started
      precociously. CONCLUSION: Even mild forms of HSP nephritis risk significant long
      term proteinuria. Very early introduction of ACEi/ARB may improve the long-term
      outcome independent of histological lesions.

PMID- 24946693
TI  - Satisfaction following immediate breast reconstruction: Experiences in the early
      post-operative stage.
AB  - OBJECTIVES: This qualitative study aimed to achieve an understanding of women's
      experiences of immediate breast reconstruction following mastectomy, to better
      understand the factors influencing patient satisfaction. DESIGN: Nine women were
      recruited from a breast unit in the North West of England. Participants were 3-9
      months post-reconstruction, had received either an implant-based or Latissimus
      Dorsi-based immediate reconstruction and were not receiving any adjuvant
      therapies. An inductive qualitative and phenomenological approach was adopted to
      data collection and analysis. METHODS: Women took part in semi-structured
      interviews. All interviews were transcribed and analysed using thematic analysis.
      RESULTS: Four themes were generated: Seeking and receiving information; coping
      with the outcome of reconstruction; the need for on-going support and a new life
      after surgery. CONCLUSION: The study highlights difficulties surrounding
      receiving information and decision-making, how women make sense of recovery, how
      they solicit and receive support, and the process by which they begin to make
      sense of their futures. More focus on these areas in service provision may aid
      positive psychological outcomes in the recovery process following immediate
      breast reconstruction.

PMID- 24946694
TI  - [Trend pattern of the incidence of thyroid cancer in Murcia Region (Spain) from
      1984 to 2008].
AB  - OBJECTIVE: To study the trend pattern of the incidence of thyroid cancer.
      METHODS: We selected incident cases of thyroid cancer occurring in the Region of
      Murcia (Spain) in 1984-2008. The variables gathered were age, sex, date of
      diagnosis, and morphology. We calculated incidence rates and the annual
      percentage of change using Bayesian age-period-cohort models. RESULTS: During the
      study period, 1414 cases were diagnosed, representing an increase in adjusted
      rates from 2.9/100000 in 1984-1988 to 7.3 in 2004-2008. The incidence was 3.5
      times higher in women than in men and the most frequent morphology was papillary
      carcinoma (67.7%). An increasing trend was found in both genders; these
      increments were more pronounced in papillary carcinoma. In women, the incidence
      increased with age, calendar year, and in those born in 1945-1963. The incidence
      of papillary microcarcinoma increased four-fold in women. CONCLUSIONS: Thyroid
      cancer used to be a rare cancer but has become an emerging tumor. The greatest
      changes were found in papillary thyroid cancer, including a gradual increase in
      the proportion of microcarcinoma.

PMID- 24946695
TI  - Treatment of atrial fibrillation: should we advocate life-style changes or
      ablation strategies to maintain sinus rhythm? Boot cAMP for atrial fibrillation.

PMID- 24946697
TI  - Intervertebral disc regeneration: a great challenge for tissue engineers.

PMID- 24946696
TI  - Effects of prenatal hypoxia on schizophrenia-related phenotypes in heterozygous
      reeler mice: a gene * environment interaction study.
AB  - Both genetic and environmental factors play important roles in the
      pathophysiology of schizophrenia. Although prenatal hypoxia is a potential
      environmental factor implicated in schizophrenia, very little is known about the
      consequences of combining models of genetic risk factor with prenatal hypoxia.
      Heterozygous reeler (haploinsufficient for reelin; HRM) and wild-type (WT) mice
      were exposed to prenatal hypoxia (9% oxygen for two hour) or normoxia at
      embryonic day 17 (E17). Behavioral (Prepulse inhibition, Y-maze and Open field)
      and functional (regional volume in frontal cortex and hippocampus as well as
      hippocampal blood flow) tests were performed at 3 months of age. The levels of
      hypoxia and stress-related molecules such as hypoxia-inducible factor-1 alpha
      (HIF-1alpha), vascular endothelial factor (VEGF), VEGF receptor-2 (VEGFR2/Flk1)
      and glucocorticoid receptor (GR) were examined in frontal cortex and hippocampus
      at E18, 1 month and 3 months of age. In addition, serum VEGF and corticosterone
      levels were also examined. Prenatal hypoxia induced anxiety-like behavior in both
      HRM and WT mice. A significant reduction in hippocampal blood flow, but no change
      in brain regional volume was observed following prenatal hypoxia. Significant age
      and region-dependent changes in HIF-1alpha, VEGF, Flk1 and GR were found
      following prenatal hypoxia. Serum VEGF and corticosterone levels were found
      decreased following prenatal hypoxia. None of the above prenatal hypoxia-induced
      changes were either diminished or exacerbated due to reelin deficiency. These
      results argue against any gene-environment interaction between hypoxia and reelin
      deficiency. 

PMID- 24946698
TI  - Rhabdomyolysis: review of the literature.
AB  - Rhabdomyolysis is a serious and potentially life threatening condition. Although
      consensus criteria for rhabdomyolysis is lacking, a reasonable definition is
      elevation of serum creatine kinase activity of at least 10 times the upper limit
      of normal followed by a rapid decrease of the sCK level to (near) normal values.
      The clinical presentation can vary widely, classical features are myalgia,
      weakness and pigmenturia. However, this classic triad is seen in less than 10% of
      patients. Acute renal failure due to acute tubular necrosis as a result of
      mechanical obstruction by myoglobin is the most common complication, in
      particular if sCK is >16.000 IU/l, which may be as high as 100,000 IU/l.
      Mortality rate is approximately 10% and significantly higher in patients with
      acute renal failure. Timely recognition of rhabdomyolysis is key for treatment.
      In the acute phase, treatment should be aimed at preserving renal function,
      resolving compartment syndrome, restoring metabolic derangements, and volume
      replacement. Most patients experience only one episode of rhabdomyolysis, mostly
      by substance abuse, medication, trauma or epileptic seizures. In case of
      recurrent rhabdomyolysis, a history of exercise intolerance or a positive family
      history for neuromuscular disorders, further investigations are needed to
      identify the underlying, often genetic, disorder. We propose a diagnostic
      algorithm for use in clinical practice.

PMID- 24946699
TI  - Effect of vermicast generated from an allelopathic weed lantana (Lantana camara)
      on seed germination, plant growth, and yield of cluster bean (Cyamopsis
      tetragonoloba).
AB  - In perhaps the first-ever study of its kind, the effect of vermicompost, derived
      solely from an allelopathic weed, on the germination, growth, and yield of a
      botanical species, has been carried out. In test plots, the soil was treated with
      the vermicompost of lantana (Lantana camara) at the rates of 5, 7.5, and 10 t ha(
      1), and cluster bean (Cyamopsis tetragonoloba) was grown on it. The performance
      of these systems was compared with the systems in which the soil was fortified
      with inorganic fertilizers (IFs) in concentrations equivalent to those present in
      the respective vermicompost (VC) treatments. Additionally, a set of control was
      studied in which the soil was used without fortification by either VC or IF. It
      was seen that up to 51.5 % greater germination success occurred in the VC
      treatments compared to controls. VC also supported better plant growth in terms
      of stem diameter, shoot length, shoot mass, number of leaves, and leaf pigments.
      The positive impact extended up to fruit yield. In addition, vermicast
      application enhanced root nodule formation, reduced disease incidence, and
      allowed for a smaller number of stunted plants. The results indicate that
      allelopathic ingredients of lantana seem to have been totally eliminated during
      the course of its vermicomposting and that lantana vermicompost has the potential
      to support germination, growth, and fruit yield better than equivalent quantities
      of IFs.

PMID- 24946700
TI  - The problem of sampling on built heritage: a preliminary study of a new non
      invasive method.
AB  - The relevance of a risk assessment of the built heritage was clearly justified
      due to the fact that it acts as a pollutant repository and hazardous pollutants
      have the capacity to penetrate into materials. However, the limitation of the
      sampling processes due to the high value of the built heritage makes a correct
      evaluation difficult. For that reason, in the present work, the potential of agar
      gels as non-invasive samplers of built heritage deterioration products, like
      crusts and patinas, was evaluated. Different gels of agar and Carbopol(r) (as
      control gel) were applied on these built surfaces considering several factors:
      the treatment time, the effectiveness of the addition of EDTA
      (ethylenediaminetetraacetic acid, C10H16N2O8) and its concentration and the use
      of a buffer at pH 7.5. All these factors were evaluated in order to determine the
      capacity of these gels as sampling systems under non-controlled atmospheric
      conditions. The results obtained in the assays were evaluated by visual
      examination, by evolution of pH and by the most important techniques used in the
      risk assessment analysis of the built heritage (Raman spectroscopy, scanning
      electron microscope (SEM)/energy dispersive X-ray (EDX) and inductively coupled
      plasma mass spectrometry (ICP-MS)). In this evaluation, the agar gels showed an
      intrinsic capacity as sampler with respect to the gel Carbopol(r) and thus, the
      best option between the studied gels consisted on agar gels with 2 % of EDTA and
      the longest application time. On the whole, the agar gels showed an interesting
      potential as non-invasive samplers of built heritage deterioration materials
      which should be studied more in depth.

PMID- 24946701
TI  - EU policy on sewage sludge utilization and perspectives on new approaches of
      sludge management.
AB  - This paper presents the current sewage sludge legislation in Europe and expected
      developments regarding the coming directives on the application of the "End-of
      waste" criteria and on fertilizers. Discussion on sludge production and
      processing is also included. The Directive 86/278 has regulated the use in
      agriculture of residual sludge from domestic and urban wastewater. After 1986,
      this directive was transposed in the different member state legislation and
      currently the national limit values on heavy metals, some organic micropollutants
      and pathogens are placed in a rather wide range. This seems the inevitable
      consequence of different attitudes towards sludge management practices in the
      member states. The discussion by the European Joint Research Center (JRC) in
      Seville regarding application of end-of-waste criteria for compost and digestate
      has produced a final document (IPTS 2014) where sludge was excluded from the
      organic wastes admitted for producing an end-of-waste compost. Sludge processing
      in Europe seems addressed to different goals: sludge minimization, full
      stabilization and hygienization by thermal hydrolysis processes before anaerobic
      digestion, and on-site incineration by fluidized bed furnace. Thermophilic
      anaerobic digestion was applied with success on the Prague WWTP with a
      preliminary lysimeter centrifugation. Coming techniques, like wet oxidation and
      pyrolysis, are applied only on very few plants. 

PMID- 24946702
TI  - PAHs in sediment cores at main river estuaries of Chaohu Lake: implication for
      the change of local anthropogenic activities.
AB  - In the present study, 28 polycyclic aromatic hydrocarbons (PAHs) were
      investigated in four sediment cores collected from the main river estuaries of
      Chaohu Lake, one of the severely polluted lakes in China. The results indicate
      that elevated concentrations of total PAHs (Sigma28PAH) were found in the samples
      from the estuary of Nanfei River (ENF), considering BaP-based total toxicity
      equivalent (TEQ-BaP) and toxic unit (TU) results; there are potential adverse
      environmental implications. The total organic carbon (TOC) played an important
      role on the accumulation of PAHs at ENF and the estuary of Tongyang River (ETY).
      The predominant PAHs are high molecular weight (HMW) homologous for all samples;
      as a result, industrial wastewater from a steel company is expectedly the key
      source of PAHs in ENF, while coke consumption would be the important source of
      PAHs at other three sampling sites. Vertical distribution of PAHs in the sediment
      cores could be explained by the local social and economic activities.
      Furthermore, a minor variation of PAH composition in the sediment core could be
      justified by the stable structure of energy consumption in the Anhui Province.
      These results justify the need for further enhancement of industrial wastewater
      treatment and development of renewable energies which are the key factors on the
      control of PAH pollution in China.

PMID- 24946703
TI  - Sources and pathways of artificial radionuclides to soils at a High Arctic site.
AB  - Activity concentrations, inventories and activity ratios of (137)Cs, (238)Pu,
      (239 + 240)Pu and (241)Am in soil profiles were surveyed in the dry tundra and
      the adjoining proglacial zones of glaciers at a High Arctic site on Svalbard.
      Vertical profiles of radionuclide activities were determined in up to 14-cm-thick
      soil sequences. Additionally, soil properties (pH, organic matter, texture,
      mineral composition and sorption capacity) were analyzed. Results obtained in
      this study revealed a large range of activity concentrations and inventories of
      the fallout radionuclides from the undetectable to the uncommonly high levels
      (inventories of 30,900 +/- 940, 47 +/- 6, 886 +/- 80 and 296 +/- 19 Bq/m(2) for
      (137)Cs, (238)Pu, (239 + 240)Pu and (241)Am, respectively) found in two profiles
      from the proglacial zone. Concentration of these initially airborne radionuclides
      in the proglacial zone soils is related to their accumulation in cryoconites that
      have a large ability to concentrate trace metals. The cryoconites develop on the
      surface of glaciers, and the material they accumulate is deposited on land
      surface after the glaciers retreat. The radionuclide inventories in the tundra
      soils, which effectively retain radionuclides due to high organic matter
      contents, were comparable to the global fallout deposition for this region of the
      world. The (238)Pu/(239 + 240)Pu activity ratios for tundra soils suggested
      global fallout as the dominant source of Pu. The (238)Pu/(239 + 240)Pu and (239 +
      240)Pu/(137)Cs activity ratios in the proglacial soils pointed to possible
      contributions of these radionuclides from other, unidentified sources.

PMID- 24946704
TI  - Performance evaluation of a continuous flow photocatalytic reactor for wastewater
      treatment.
AB  - A novel photocatalytic reactor for wastewater treatment was designed and
      constructed. The main part of the reactor was an aluminum tube in which 12
      stainless steel circular baffles and four quartz tube were placed inside of the
      reactor like shell and tube heat exchangers. Four UV-C lamps were housed within
      the space of the quartz tubes. Surface of the baffles was coated with TiO2. A
      simple method was employed for TiO2 immobilization, while the characterization of
      the supported photocatalyst was based on the results obtained through performing
      some common analytical methods such as X-ray diffraction (XRD), scanning electron
      microscope (SEM), and BET. Phenol was selected as a model pollutant. A solution
      of a known initial concentration (20, 60, and 100 ppmv) was introduced to the
      reactor. The reactor also has a recycle flow to make turbulent flow inside of the
      reactor. The selected recycle flow rate was 7 * 10(-5) m(3).s(-1), while the flow
      rate of feed was 2.53 * 10(-7), 7.56 * 10(-7), and 1.26 * 10(-6) m(3).s(-1),
      respectively. To evaluate performance of the reactor, response surface
      methodology was employed. A four-factor three-level Box-Behnken design was
      developed to evaluate the reactor performance for degradation of phenol. Effects
      of phenol inlet concentration (20-100 ppmv), pH (3-9), liquid flow rate (2.53 *
      10(-7)-1.26 * 10(-6) m(3).s(-1)), and TiO2 loading (8.8-17.6 g.m(-2)) were
      analyzed with this method. The adjusted R (2) value (0.9936) was in close
      agreement with that of corresponding R (2) value (0.9961). The maximum predicted
      degradation of phenol was 75.50 % at the optimum processing conditions (initial
      phenol concentration of 20 ppmv, pH ~ 6.41, and flow rate of 2.53 * 10(-7)
      m(3).s(-1) and catalyst loading of 17.6 g.m(-2)). Experimental degradation of
      phenol determined at the optimum conditions was 73.7 %. XRD patterns and SEM
      images at the optimum conditions revealed that crystal size is approximately 25
      nm and TiO2 nanoparticles with visible agglomerates distribute densely and
      uniformly over the surface of stainless steel substrate. BET specific surface
      area of immobilized TiO2 was 47.2 and 45.8 m(2) g(-1) before and after the
      experiments, respectively. Reduction in TOC content, after steady state
      condition, showed that maximum phenol decomposition occurred at neutral condition
      (pH ~ 6).

PMID- 24946705
TI  - Combining phytoextraction and ecocatalysis: a novel concept for greener
      chemistry, an opportunity for remediation.

PMID- 24946706
TI  - Evaluation of heavy metal and polycyclic aromatic hydrocarbons accumulation in
      plants from typical industrial sites: potential candidate in phytoremediation for
      co-contamination.
AB  - The heavy metal and polycyclic aromatic hydrocarbons (PAHs) contents were
      evaluated in surface soil and plant samples of 18 wild species collected from 3
      typical industrial sites in South Central China. The accumulative characteristics
      of the plant species for both heavy metal and PAHs were discussed. The
      simultaneous accumulation of heavy metal and PAHs in plant and soil was observed
      at all the investigated sites, although disparities in spatial distributions
      among sites occurred. Both plant and soil samples were characterized by high
      accumulation for heavy metal at smelting site, moderate enrichment at coke power
      and coal mining sites, whereas high level of PAHs (16 priority pollutants
      according to US Environmental Protection Agency) at coke power site, followed
      sequentially by coal mining and smelting sites. Based on the differences of heavy
      metal and PAH accumulation behaviors of the studied plant species, heavy metal
      and PAH accumulation strategies were suggested: Pteris vittata L. and Pteris
      cretica L. for As and PAHs, Boehmeria nivea (L.) Gaud for Pb, As, and PAHs, and
      Miscanthus floridulu (Labnll.) Warb for Cu and PAHs. These native plant species
      could be proposed as promising materials for heavy metal and PAHs combined
      pollution remediation.

PMID- 24946707
TI  - Photocatalytic ozonation of terephthalic acid: a by-product-oriented
      decomposition study.
AB  - Terephthalic acid (TA) is considered as a refractory model compound. For this
      reason, the TA degradation usually requires a prolonged reaction time to achieve
      mineralization. In this study, vanadium oxide (VxOy) supported on titanium oxide
      (TiO2) served as a photocatalyst in the ozonation of the TA with light-emitting
      diodes (LEDs), having a bandwidth centered at 452 nm. The modified catalyst
      (VxOy/TiO2) in combination with ozone and LEDs improved the TA degradation and
      its by-products. The results obtained by this system were compared with
      photolysis, single ozonation, catalytic ozonation, and photocatalytic ozonation
      of VxOy/TiO2 with UV lamp. The LED-based photocatalytic ozonation showed almost
      the same decomposition efficiency of the TA, but it was better in comparison with
      the use of UV lamp. The oxalic acid accumulation, as the final product of the TA
      decomposition, was directly influenced by either the presence of VxOy or/and the
      LED irradiation. Several by-products formed during the TA degradation, such as
      muconic, fumaric, and oxalic acids, were identified. Besides, two unidentified by
      products were completely removed during the observed time (60 min). It was
      proposed that the TA elimination in the presence of VxOy/TiO2 as catalyst was
      carried out by the combination of different mechanisms: molecular ozone reaction,
      indirect mechanism conducted by .OH, and the surface complex formation.

PMID- 24946708
TI  - Comparative performance of descriptors in a multiple linear and Kriging models: a
      case study on the acute toxicity of organic chemicals to algae.
AB  - This study presents quantitative structure-toxicity relationship (QSTR) models on
      the toxicity of 91 organic compounds to Chlorella vulgaris using multiple linear
      regression (MLR) and Kriging techniques. The molecular descriptors were
      calculated using SPARTAN and DRAGON programs, and descriptor selection was made
      by "all subset" method available in the QSARINS software. MLR and Kriging models
      developed with the same descriptors were compared. In addition to these models,
      Kriging method was used for descriptor selection, and model development. The
      selected descriptors showed the importance of hydrophobicity, molecular weight
      and atomic ionization state in describing the toxicity of a diverse set of
      chemicals to C. vulgaris. A QSTR model should be associated with appropriate
      measures of goodness-of-fit, robustness, and predictivity in order to be used for
      regulatory purpose. Therefore, while the internal performances (goodness-of-fit
      and robustness) of the models were determined by using a training set, the
      predictive abilities of the models were determined by using a test set. The
      results of the study showed that while MLR method is easier to apply, the Kriging
      method was more successful in predicting toxicity. 

PMID- 24946709
TI  - Enhancement of in vitro high-density polyethylene (HDPE) degradation by physical,
      chemical, and biological treatments.
AB  - Partially degraded high-density polyethylene (HDPE) was collected from plastic
      waste dump yard for biodegradation using fungi. Of various fungi screened, strain
      MF12 was found efficient in degrading HDPE by weight loss and Fourier transform
      infrared (FT-IR) spectrophotometric analysis. Strain MF12 was selected as
      efficient HDPE degraders for further studies, and their growth medium composition
      was optimized. Among those different media used, basal minimal medium (BMM) was
      suitable for the HDPE degradation by strain MF12. Strain MF12 was subjected to
      28S rRNA sequence analysis and identified as Aspergillus terreus MF12. HDPE
      degradation was carried out using combinatorial physical and chemical treatments
      in conjunction to biological treatment. The high level of HDPE degradation was
      observed in ultraviolet (UV) and KMnO4/HCl with A. terreus MF12 treatment, i.e.,
      FT10. The abiotic physical and chemical factors enhance the biodegradation of
      HDPE using A. terreus MF12.

PMID- 24946710
TI  - The 14th EuCheMS International Conference on Chemistry and the Environment (ICCE
      2013, Barcelona, June 25-28, 2013).

PMID- 24946711
TI  - Effect of crude oil contamination on the chlorophyll content and morpho-anatomy
      of Cyperus brevifolius (Rottb.) Hassk.
AB  - Chlorophyll plays a pivotal role in the plant physiology and its productivity.
      Cultivation of plants in crude oil contaminated soil has a great impact on the
      synthesis of chlorophyll pigment. Morpho-anatomy of the experimental plant also
      shows structural deformation in higher concentrations. Keeping this in mind, a
      laboratory investigation has been carried out to study the effect of crude oil on
      chlorophyll content and morpho-anatomy of Cyperus brevifolius plant. Fifteen-day
      old seedling of the plant was planted in different concentrations of the crude
      oil mixed soil (i.e., 10,000, 20,000, 30,000, 40,000, and 50,000 ppm). A control
      setup was also maintained without adding crude oil. Results were recorded after 6
      months of plantation. Investigation revealed that there is a great impact of
      crude oil contamination on chlorophyll content of the leaves of the experimental
      plant. It also showed that chlorophyll a, chlorophyll b, and total chlorophyll
      content of leaves grown in different concentrations of crude oil were found to be
      lower than those of the control plant. Further, results also demonstrated that
      chlorophyll content was lowest in the treatment that received maximum dose of
      crude oil. It also showed that chlorophyll content was decreased with increased
      concentration of crude oil. Results also demonstrated that there was a reduction
      in plant shoot and root biomass with the increase of crude oil concentration.
      Results also revealed that the shoot biomass is higher than root biomass.
      Morphology and anatomy of the experimental plant also show structural deformation
      in higher concentrations. Accumulation of crude oil on the cuticle of the
      transverse section of the leaves and shoot forms a thick dark layer. Estimation
      of the level of pollution in an environment due to oil spill is possible by the
      in-depth study of the harmful effects of oil on the morphology and anatomy and
      chlorophyll content of the plants grown in that particular environment.

PMID- 24946712
TI  - International cross-validation of a BOD5 surrogate.
AB  - BOD5 dates back to 1912 when the Royal Commission decided to use the mean
      residence time of water in the rivers of England, 5 days, as a standard to
      measure the biochemical oxygen demand. Initially designed to protect the quality
      of river waters from extensive sewage discharge, the use of BOD5 has been quickly
      extended to waste water treatment plants (WWTPs) to monitor their efficiency on a
      daily basis. The measurement has been automatized but remains a tedious, time-
      and resource-consuming analysis. We have cross-validated a surrogate BOD5 method
      on two sites in France and in the USA with a total of 109 samples. This method
      uses a fluorescent redox indicator on a 96-well microplate to measure microbial
      catabolic activity for a large number of samples simultaneously. Three
      statistical tests were used to compare surrogate and reference methods and showed
      robust equivalence.

PMID- 24946713
TI  - Electron multiplying charge-coupled device-based fluorescence cross-correlation
      spectroscopy for blood velocimetry on zebrafish embryos.
AB  - Biomedical issues in vasculogenesis and cardiogenesis require methods to follow
      hemodynamics with high spatial (micrometers) and time (milliseconds) resolution.
      At the same time, we need to follow relevant morphogenetic processes on large
      fields of view. Fluorescence cross-correlation spectroscopy coupled to scanning
      or wide-field microscopy meets these needs but has limited flexibility in the
      excitation pattern. To overcome this limitation, we develop here a two-photon two
      spots setup coupled to an all-reflective near-infrared (NIR) optimized scanning
      system and to an electron multiplying charge-coupled device. Two NIR laser spots
      are spaced at adjustable micron-size distances (1 to 50 MUm) by means of a Twyman
      Green interferometer and repeatedly scanned on the sample, allowing acquisition
      of information on flows at 4 ms-3 MUm time-space resolution in parallel on an
      extended field of view. We analyze the effect of nonhomogeneous and variable flow
      on the cross-correlation function by numerical simulations and show exemplary
      application of this setup in studies of blood flow in zebrafish embryos in vivo.
      By coupling the interferometer with the scanning mirrors and by computing the
      cross-correlation function of fluorescent red blood cells, we are able to map
      speed patterns in embryos' vessels.

PMID- 24946714
TI  - Complete mitochondrial genome sequences of two parasitic/commensal nemerteans,
      Gononemertes parasita and Nemertopsis tetraclitophila (Nemertea: Hoplonemertea).
AB  - BACKGROUND: Most nemerteans (phylum Nemertea) are free-living, but about 50
      species are known to be firmly associated with other marine invertebrates. For
      example, Gononemertes parasita is associated with ascidians, and Nemertopsis
      tetraclitophila with barnacles. There are 12 complete or near-complete
      mitochondrial genome (mitogenome) sequences of nemerteans available in GenBank,
      but no mitogenomes of none free-living nemerteans have been determined so far. In
      the present paper complete mitogenomes of the above two parasitic/commensal
      nemerteans are reported. METHODS: The complete mitochondrial genomes (mitogenome)
      of G. parasita and N. tetraclitophila were amplified by conventional and long
      PCR. Phylogenetic analyses of maximum likelihood (ML) and Bayesian inference (BI)
      were performed with both concatenated nucleotide and amino acid sequences.
      RESULTS: Complete mitogenomes of G. parasita and N. tetraclitophila are 14742 bp
      and 14597 bp in size, respectively, which are within the range of published
      Hoplonemertea mitogenomes. Their gene orders are identical to that of published
      Hoplonemertea mitogenomes, but different from those of Palaeo- and Heteronemertea
      species. All the coding genes, as well as major non-coding regions (mNCRs), are
      AT rich, which is especially pronounced at the third codon position. The AT/GC
      skew pattern of the coding strand is the same among nemertean mitogenomes, but is
      variable in the mNCRs. Some slight differences are found between mitogenomes of
      the present species and other hoplonemerteans: in G. parasita the mNCR is biased
      toward T and C (contrary to other hoplonemerteans) and the rrnS gene has a unique
      58-bp insertion at the 5' end; in N. tetraclitophila the nad3 gene starts with
      the ATT codon (ATG in other hoplonemerteans). Phylogenetic analyses of the
      nucleotide and amino acid datasets show early divergent positions of G. parasita
      and N. tetraclitophila within the analyzed Distromatonemertea species, and
      provide strong support for the close relationship between Hoplonemertea and
      Heteronemertea. CONCLUSION: Gene order is highly conserved within the order
      Monostilifera, particularly within the Distromatonemertea, and the special
      lifestyle of G. parasita and N. tetraclitophila does not bring significant
      variations to the overall structures of their mitogenomes in comparison with free
      living hoplonemerteans.

PMID- 24946715
TI  - Determination of energy level alignment at metal/molecule interfaces by in-device
      electrical spectroscopy.
AB  - The energetics of metal/molecular semiconductor interfaces plays a fundamental
      role in organic electronics, determining the performance of very diverse devices.
      So far, information about the energy level alignment has been most commonly
      gained by spectroscopy techniques that typically require experimental conditions
      far from the real device operation. Here we demonstrate that a simple three
      terminal device allows the acquisition of spectroscopic information about the
      metal/molecule energy alignment in real operative condition. As a proof of
      principle, we employ the proposed device to measure the energy barrier height
      between different clean metals and C60 molecules and we recover typical results
      from photoemission spectroscopy. The device is designed to inject a hot electron
      current directly into the molecular level devoted to charge transport,
      disentangling the contributions of both the interface and the bulk to the device
      total resistance, with important implications for spintronics and low-temperature
      physics. 

PMID- 24946716
TI  - A ray of venom: Combined proteomic and transcriptomic investigation of fish venom
      composition using barb tissue from the blue-spotted stingray (Neotrygon kuhlii).
AB  - Fish venoms remain almost completely unstudied despite the large number of
      species. In part this is due to the inherent nature of fish venoms, in that they
      are highly sensitive to heat, pH, lyophilisation, storage and repeated freeze
      thawing. They are also heavily contaminated with mucus, which makes proteomic
      study difficult. Here we describe a novel protein-handling protocol to remove
      mucus contamination, utilising ammonium sulphate and acetone precipitation. We
      validated this approach using barb venom gland tissue protein extract from the
      blue-spotted stingray Neotrygon kuhlii. We analysed the protein extract using 1D
      and 2D gels with LC-MS/MS sequencing. Protein annotation was underpinned by a
      venom gland transcriptome. The composition of our N. kuhlii venom sample revealed
      a variety of protein types that are completely novel to animal venom systems.
      Notably, none of the detected proteins exhibited similarity to the few toxin
      components previously characterised from fish venoms, including those found in
      other stingrays. Putative venom toxins identified here included cystatin,
      peroxiredoxin and galectin. Our study represents the first combined survey of
      gene and protein composition from the venom apparatus of any fish and our novel
      protein handling method will aid the future characterisation of toxins from other
      unstudied venomous fish lineages. BIOLOGICAL SIGNIFICANCE: These results show an
      efficient manner for removing mucus from fish venoms. These results are the first
      insights into the evolution of proteins present on stingrayvenom barbs.

PMID- 24946717
TI  - Systematic synthesis of sulfated oligofucosides and their effect on breast cancer
      MCF-7 cells.
AB  - Sulfated tetrafucosides with different sulfation patterns, and a non-sulfated
      tetrafucoside , were designed and systematically synthesized from the common key
      intermediate . In addition, their anti-proliferative activities and apoptosis
      inducing activities against human breast cancer MCF-7 cells were evaluated. Our
      results demonstrated that the sulfated tetrafucosides reduced the number of MCF-7
      cells in a dose-dependent manner, and of these, 3,4-O-sulfated type showed the
      highest anti-proliferative activity, comparable to the activity of fucoidan
      isolated from Fucus vesiculosus. Furthermore, it was revealed that both and
      exhibited apoptosis-inducing activities through activation of caspase-8 on MCF-7
      cells. 

PMID- 24946718
TI  - Hematopoietic cell transplantation for plasmablastic lymphoma: a review.
AB  - Plasmablastic lymphoma (PBL) is recognized by the World Health Organization as a
      very aggressive subtype of non-Hodgkin lymphoma. It was initially described in
      the setting of human immunodeficiency virus (HIV) infection, but it has since
      been identified in immunocompetent patients, as well. PBL is characterized by
      CD20 negativity and is associated with Epstein-Barr virus infection. The outcome
      with available therapy is poor, with median survival of less than 1 year.
      Multiple adverse prognostic factors have been identified, including HIV
      negativity, MYC gene rearrangement, high-risk international prognostic index, and
      not achieving complete remission after induction therapy. The role of
      intensification of induction chemotherapy is controversial. Novel agents have
      shown some activity in relapsed setting and may have a role in upfront line of
      treatment. The outcome for relapsed PBL is dismal. Autologous hematopoietic cell
      transplantation (AHCT) appears to be feasible and may produce better results than
      chemotherapy, but definitive data are sparse. Chemosensitivity before
      transplantation might be required to benefit from such therapy. Some data suggest
      a better outcome of PBL if consolidation with AHCT is used in first-line setting,
      particularly for those with high-risk disease. 

PMID- 24946719
TI  - Unrelated cord blood transplantation for patients with primary or secondary
      myelofibrosis.
AB  - To determine whether umbilical cord blood transplantation (UCBT) is an
      alternative cure for myelofibrosis (MF), we evaluated 35 UCBTs reported to
      Eurocord. Seven patients had secondary acute myeloid leukemia (AML) at UCBT, and
      median age at UCBT was 54 years. Twenty-four patients received a reduced
      intensity conditioning (RIC) regimen, and 17 of 35 patients received total body
      irradiation (2 to 12 Gy)-fludarabine-cyclophosphamide (TCF) conditioning. The
      median follow-up was 24 months. The cumulative incidence of neutrophil recovery
      at 60 days was 80%. Fifteen patients relapsed after UCBT. The 2-year overall
      survival and event-free-survival (EFS) rates were 44% and 30%, respectively. All
      patients given TCF achieved neutrophil and platelet recovery, and the use of TCF
      was associated with superior EFS in the RIC population (44% versus 0%, P = .001).
      Patients with transformation to AML had similar outcomes to patients with less
      advanced stages. In conclusion, despite graft failure remaining a major concern,
      the role of UCBT in the management of MF, especially using RIC TCF-based
      regimens, deserves further investigation to improve results.

PMID- 24946720
TI  - Deciphering the role of the chitin synthase families 1 and 2 in the in vivo and
      in vitro growth of Aspergillus fumigatus by multiple gene targeting deletion.
AB  - Although chitin is an essential component of the fungal cell wall (CW), its
      biosynthesis and role in virulence is poorly understood. In Aspergillus
      fumigatus, there are eight chitin synthase (CHS) genes belonging to two families
      CHSA-C, CHSG in family 1 and CHSF, CHSD, CSMA, CSMB in family 2). To understand
      the function of these CHS genes, their single and multiple deletions were
      performed using beta-rec/six system to be able to delete all genes within each
      family (up to a quadruple DeltachsA/C/B/G mutant in family 1 and a quadruple
      DeltacsmA/csmB/F/D mutant in family 2). Radial growth, conidiation,
      mycelial/conidial morphology, CW polysaccharide content, Chs-activity,
      susceptibility to antifungal molecules and pathogenicity in experimental animal
      aspergillosis were analysed for all the mutants. Among the family 1 CHS,
      DeltachsA, DeltachsB and DeltachsC mutants showed limited impact on chitin
      synthesis. In contrast, there was reduced conidiation, altered mycelial
      morphotype and reduced growth and Chs-activity in the DeltachsG and
      DeltachsA/C/B/G mutants. In spite of this altered phenotype, these two mutants
      were as virulent as the parental strain in the experimental aspergillosis models.
      Among family 2 CHS, phenotypic defects mainly resulted from the CSMA deletion.
      Despite significant morphological mycelial and conidial growth phenotypes in the
      quadruple DeltacsmA/csmB/F/D mutant, the chitin content was poorly affected by
      gene deletions in this family. However, the entire mycelial cell wall structure
      was disorganized in the family 2 mutants that may be related to the reduced
      pathogenicity of the quadruple DeltacsmA/csmB/F/D mutant strain compared to the
      parental strain, in vivo. Deletion of the genes encompassing the two families
      (DeltacsmA/csmB/F/G) showed that in spite of being originated from an ancient
      divergence of fungi, these two families work cooperatively to synthesize chitin
      in A. fumigatus and demonstrate the essentiality of chitin biosynthesis for
      vegetative growth, resistance to antifungal drugs, and virulence of this
      filamentous fungus.

PMID- 24946721
TI  - Expression of TGFbeta-1 and EHD1 correlated with survival of non-small cell lung
      cancer.
AB  - Transforming growth factor-beta1 (TGFbeta-1) signaling is regulated by
      endocytotic pathway. To clarify the prognostic value of TGFbeta-1 and to verify
      the involvement of endocytosis in drug resistance, we examined the expression of
      TGFbeta-1 and Eps15 homology domain 1 (EHD1) in non-small cell lung cancer
      (NSCLC) and its association with tumor characteristics and survival of patients
      with NSCLC. Expression of TGFbeta-1 and EHD1 was evaluated by
      immunohistochemistry in paraffin sections from 105 NSCLC patients. Overall
      survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and
      multivariate Cox proportional hazard regression model. Positive immunostaining of
      TGFbeta-1 and EHD1 was detected in 52.38 and 39.05 % of NSCLC samples,
      respectively. In non-adjuvant chemotherapy-treated group (P = 0.006) and
      epidermal growth factor receptor (EGFR) (+) group (P = 0.038), patients with
      TGFbeta-1 expression had a longer OS. EHD1 negative expression predicted a longer
      OS (P = 0.003), especially in EGFR (+) (P = 0.006) and adjuvant chemotherapy
      treated patients (P = 0.003). NSCLC patients with concurrent positive TGFbeta-1
      and negative EHD1 (combined markers) were significantly correlated with better OS
      (P = 0.001). American Joint Committee on Cancer (AJCC) status and combined
      markers were independent prognostic indicators for OS (HR (95 % CI) 1.576 (1.112
      2.232), P = 0.011 and HR 0.349 (0.180-0.673), P = 0.002, respectively). We
      identified concordant TGFbeta-1 positive and EHD1 negative as a strong favorable
      prognosis factor in NSCLC. Our results may help us to select and optimize
      strategies for individualized therapy.

PMID- 24946722
TI  - PLGF inhibition impairs metastasis of larynx carcinoma through MMP3
      downregulation.
AB  - Cancer neovascularization plays a key role in the metastasis of larynx carcinoma.
      However, the molecular mechanism for the neovascularization control in larynx
      carcinoma is poorly understood. Since placental growth factor (PLGF) has been
      reported to be involved in pathological angiogenesis, and since matrix
      metalloproteinases (MMPs) are essential for extracellular matrix degradation
      during neovascularization, here we were prompted to examine whether PLGF and MMPs
      may play a coordinate role in the metastasis of larynx carcinoma. Our data showed
      that the expression of PLGF and MMP3 strongly correlated in the larynx carcinoma
      in the patients, and significant higher levels of PLGF and MMP3 were detected in
      the larynx carcinoma from the patients with metastasis of the primary cancer.
      Thus, we used a human larynx carcinoma cell line, Hep-2, to examine whether
      expression of PLGF and MMP3 may affect each other. We found that overexpression
      of PLGF in Hep-2 cells increased expression of MMP3, while inhibition of PLGF in
      Hep-2 cells decreased expression of MMP3. However, neither overexpression, nor
      inhibition of MMP3 in Hep-2 cells affected the expression level of PLGF. These
      data suggest that PLGF may function upstream of MMP3 in larynx carcinoma cells.
      We then analyzed how PLGF affected MMP3. Application of a specific ERK1/2
      inhibitor to PLGF-overexpressing Hep-2 cells substantially abolished the effect
      of PLGF on MMP3 activation, suggesting that PLGF may increase expression of MMP3
      via ERK/MAPK signaling pathway. Since anti-PLGF was recently applied in clinical
      trials to inhibit cancer-related angiogenesis, here our data further demonstrate
      that inhibition of cancer neovascularization by anti-PLGF is mediated not only by
      direct effect on endothelial growth and capillary permeability, but also by
      indirect effect via MMP3 on the extracellular matrix degradation in larynx
      carcinoma.

PMID- 24946723
TI  - The relationship between disease activity measured by the BASDAI and
      psychological status, stressful life events, and sleep quality in ankylosing
      spondylitis.
AB  - Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a standard
      instrument regularly used to assess disease activity of patients with ankylosing
      spondylitis (AS). However, the well-being of a patient is also affected by
      impairment of function as well as psychological status and other factors. The
      objective of this study was to evaluate if psychological status, stressful life
      events, and sleep quality contribute significantly to BASDAI. Six hundred eighty
      three AS patients satisfying the Modified New York Criteria for AS were recruited
      from the rheumatology clinics of seven hospitals in China. Patients with other
      concomitant disorders were excluded. Participants were requested to complete a
      set of clinical examinations and the following questionnaires: Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis
      Functional Index (BASFI), Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating
      Depression Scale (SDS), Pittsburgh Sleep Quality Index Questionnaire (PSQI),
      Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and Social
      Readjustment Rating Scale (SRRS). Spearman correlation analysis showed that
      BASDAI was highly associated with degree and duration of morning stiffness,
      overall pain, nocturnal back pain, overall back pain, anxiety, and BASFI (all P <
      0.001), but were not associated with education, HAQ-S, and sleep medication in
      PSQI (P > 0.05). Multiple stepwise regression analysis indicated that overall
      pain was the maximal statistical contribution in predicting disease activity
      (standardized coefficient, 0.335). In hierarchic multiple regression analysis,
      psychological variables added an only additional 2.7% to the overall R(2) beyond
      that accounted for by demographic and medical variables, resulting in a final
      R(2) of 53.5%. Although BASDAI is a very good measurement of pain and stiffness
      and to a certain extent effect of functional impairment in AS, it barely takes
      into account psychological status, stress life events, and sleep quality These
      factors should be evaluated by other modalities.

PMID- 24946724
TI  - Assessment of immunogenic characteristics of Hemiscorpius lepturus venom and its
      cross-reactivity with venoms from Androctonus crassicauda and Mesobuthus eupeus.
AB  - Hemiscorpius lepturus (H. lepturus), one of the most venomous scorpions in
      tropical and sub-tropical areas, belongs to the Hemiscorpiidae family. Studies of
      antibodies in sera against the protein component of the venom from this organism
      can be of great use for the development of engineered variants of proteins for
      eventual use in the diagnosis/treatment of, and prevention of reactions to,
      stings. In the present in vitro study, the proteins of H. lepturus venom, which
      could specifically activate the production of immunoglobulin G (IgG) in victims
      accidently exposed to the venom from this scorpion, were evaluated and their
      cross-reactivity with venoms from two other important scorpion species including
      Androctonus crassicauda and Mesobuthus eupeus assessed. H. lepturus venom was
      analyzed with respect to its protein composition and its antigenic properties
      against antibodies found in sera collected from victims exposed to the venom of
      this scorpion within a previous 2-month period. The cross-reactivity of the H.
      lepturus venom with those from A. crassicauda and M. eupeus was assessed using
      ELISA and immunoblotting. Electrophoretic analysis of the venom of H. lepturus
      revealed several protein bands with weights of 8-116 KDa. The most frequent IgG
      reactive bands in the test sera had weights of 34, 50, and 116 kDa. A weak cross
      reactivity H. lepturus of venom with venoms from A. crassicauda and M. eupeus was
      detected. The results of immunoblotting and ELISA experiments revealed that H.
      lepturus venom activated the host immune response, leading to the production of a
      high titer of antibodies. Clearly, a determination of the major immunogenic
      components of H. lepturus venom could be valuable for future studies and
      ultimately of great importance for the potential production of recombinant or
      hypo-venom variants of these proteins.

PMID- 24946725
TI  - Prevalence of anemia among under-5 children in the Ghanaian population: estimates
      from the Ghana demographic and health survey.
AB  - BACKGROUND: Anemia in children continues to be a major public health challenge in
      most developing countries, particularly in Africa. Anemia in the early stages of
      life leads to severe negative consequences on the cognitive as well as the growth
      and development of children, which may persist even after treatment. We examine
      the prevalence of anemia in under-five children in the Ghanaian population to
      help inform and serve as a guide to health policies and possible interventions.
      METHODS: Data from the 2008 Ghana Demographic and Health Survey (GDHS) was used.
      Data consists of health, demographic and socio-economic factors. Anemia status
      was determined using hemoglobin level, and prevalence of childhood anemia along
      with 95% confidence intervals was provided. We also examined the distribution of
      prevalence across different age and socio-demographic groups as well as the
      different regions and sub-regions in Ghana. RESULTS: The overall prevalence of
      anemia in under-five children in Ghana was 78.4% (N = 2168, 95% CI: 76.7-80.2),
      where 7.8% (N = 2168, 95% CI: 6.6-8.9) of the children had severe anemia, 48.0%
      (N = 2168, 95% CI: 45.9-50.2) moderate anemia and 22.6% (N = 2168, 95% CI: 20.8
      24.4) had mild anemia. The highest prevalence regions were the Upper East, 88.9%
      (N = 158, 95% CI: 80.9-94.0), and Upper West 88.1% (N = 220, 95% CI: 76.4-94.6).
      The prevalence was also higher among children under 2 years of age, 85.1% (N =
      781, 95% CI: 82.6-87.7) than children 2-5 years of age, 74.8% (N = 1387, 95% CI:
      72.5-77.1). No significant difference in prevalence between boys and girls was
      observed. CONCLUSIONS: Given the high prevalence of childhood anemia observed in
      Ghana, particularly among those less than 2 years old, and given the negative
      consequences on their cognitive and behavioral development even in later years,
      there is an urgent need for effective and efficient public health interventions.

PMID- 24946726
TI  - Surgical Team Assessment Training: improving surgical teams during deployment.
AB  - BACKGROUND: Simulation and team training are accepted as critical patient safety
      strategies to improve team performance and can help achieve better outcomes.
      Standardized and realistic drills conducted by skilled physicians and nurses who
      demonstrate consistent use of principles which enhance communication and teamwork
      increase the likelihood of improved clinical outcomes. METHODS: Two, 4-member
      surgeon/nurse teams traveled to 8 Army surgical resuscitation medical treatment
      facilities in Iraq during July and August 2011. At each site, a new program
      called Surgical Team Assessment Training was introduced and implemented to 220
      military personnel. Two multi-patient scenarios were designed to test
      resuscitative and operating room medical decision-making, communication, and co
      ordination of care. In addition, 2 hours of didactic instruction emphasized
      principles of TeamSTEPPS applied to emergency and operating rooms during care of
      patients with multiple, complex traumatic injuries. Anonymous surveys were
      completed by participants following the training. RESULTS: Participants were
      significantly more likely to rate this training as very helpful following
      training compared with their opinion before participation (53% vs 37%, P < .05).
      Seventy-seven percent felt that it would improve overall patient outcomes, 78%
      said it would likely contribute to saving lives in combat, and 98% felt it should
      be provided to military Emergency Medicine and Surgical residents. CONCLUSIONS:
      Surgical Team Assessment Training can be successfully implemented in an austere,
      hostile environment and improve trauma team function by incorporating simulation
      training models and TeamSTEPPs concepts. Expansion of this program for
      predeployment and resident training is currently under investigation based on the
      extremely positive responses.

PMID- 24946728
TI  - Highly efficient and reversible iodine capture using a metalloporphyrin-based
      conjugated microporous polymer.
AB  - A new metalloporphyrin-based conjugated microporous polymer, NiP-CMP, was
      constructed via a homo-coupling polymerization reaction. NiP-CMP possesses a high
      BET surface area of over 2600 m(2) g(-1), a large pore volume of 2.288 cm(3) g(
      1), good stability, and displays excellent guest uptake of 202 wt% in iodine
      vapour. We also highlight that the polymer exhibits outstanding performance for
      the reversible adsorption of iodine in solution. 

PMID- 24946727
TI  - Breast cancer recurrence after nipple-sparing mastectomy: one institution's
      experience.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) has been increasingly used to treat
      women with breast cancer who wish to preserve the overlying breast skin, but
      concern remains regarding tumor recurrence. We report our experience performing
      NSM for breast cancer treatment and prophylaxis over a 6-year period. METHODS: A
      retrospective chart review on patients undergoing NSM or skin-sparing mastectomy
      (SSM) from 2005 to 2011 was performed. RESULTS: NSM patients were younger (P <
      .001), had a lower body mass index (P < .001), and were associated with a family
      cancer risk (P = .01) but not genetic risk (P = .83). There was no difference in
      the distance between the tumor and the nipple-areola complex when comparing NSM
      and SSM (P = .47). There was no significant difference in recurrence (P = .08) or
      survival (P = .38) when comparing NSM and SSM after controlling for age, stage,
      and surgery laterality. CONCLUSIONS: There was no difference in survival or
      cancer recurrence for NSM or SSM. NSM does not increase the risk of recurrence or
      decrease survival.

PMID- 24946729
TI  - Application of the 2013 American Urological Association early detection of
      prostate cancer guideline: who will we miss?
AB  - PURPOSE: The American Urological Association (AUA) published new prostate cancer
      (CaP) screening guidelines in 2013. We apply the guidelines to a retrospective
      cohort to compare tumor characteristics of those no longer recommended for
      screening with those who remain screening candidates. METHODS: We identified
      cases of screening detected CaP (stage cT1c) in the Surveillance Epidemiology and
      End Results database from October 2005 to December 2010. The 2013 AUA Guidelines
      were retrospectively applied to the cohort. Men were categorized into three
      groups for comparison based on whether or not they would now be recommended for
      CaP screening (Unscreened, Young Unscreened, and Screened). We compared clinical
      and pathological characteristics of CaP across study groups. RESULTS: A total of
      142,382 men were identified. Screening would no longer be recommended for 40,160.
      Those no longer recommended for screening had higher median PSA (6.4 vs. 5.8
      ng/mL, p < 0.01), more Gleason 7 and >=8 CaP on prostate biopsy (36.4 vs. 34.8 %,
      p < 0.001; 12.4 vs. 9.2 %, p < 0.001, respectively) and slightly more Gleason >=8
      CaP (9.0 vs. 7.5 %, p = 0.03), and T3 tumors (17.3 vs. 16.5 %, p = 0.01) at
      prostatectomy. Nodal and distant metastasis rates were clinically equivalent
      among men screened and unscreened. Subgroup analysis of young patients (40-54
      years old) no longer recommended for screening identified intermediate or high
      risk Gleason scores at prostatectomy 57.6 % of the time. CONCLUSIONS: Features of
      CaP in men no longer recommended for routine screening are largely equivalent to
      if not worse than those in screened men.

PMID- 24946730
TI  - Methods of split reporter reconstitution for the analysis of biomolecules.
AB  - Intracellular signaling inside living cells is controlled by the specific
      localization of biomolecules, including proteins, with timescales ranging from
      milliseconds to several hours. To elucidate the related spatial and temporal
      signal processes, development of optical probes for cellular events is a
      challenging task in present studies. Herein, we describe recent advances in the
      basic design of the optical probes, which have been inspired by luminescent
      creatures, and their practical application to visualize intracellular events in
      living cells and animals. A discussion of different probe designs reveals their
      benefits and shortcomings. 

PMID- 24946731
TI  - Pd0-mediated rapid cross-coupling reactions, the rapid C-[11C]methylations,
      revolutionarily advancing the syntheses of short-lived PET molecular probes.
AB  - Positron emission tomography is a noninvasive method for monitoring drug (or
      diagnostic) behavior and its localization on the target molecules in the living
      systems, including the human body, using a short-lived positron-emitting
      radionuclide. New methodologies for introducing representative short-lived
      radionuclides, (11)C and (18)F, into the carbon frameworks of biologically active
      organic compounds have been established by developing rapid C-[(11)C]methylations
      and C-[(18)F]fluoromethylations using rapid Pd(0)-mediated cross-coupling
      reactions between [(11)C]methyl iodide (sp(3)-hybridized carbon) and an excess
      amount of organotributylstannane or organoboronic acid ester having sp(2)
      (phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp(3) (benzyl and cinnamyl)
      hybridized carbons; and [(18)F]fluoromethyl halide (iodide or bromide) and an
      organoboronic acid ester, respectively. These rapid reactions provide a firm
      foundation for an efficient and general synthesis of short-lived (11)C- or (18)F
      labeled PET molecular probes to promote in vivo molecular imaging studies.

PMID- 24946737
TI  - Atypical fibroxanthoma: a series of 56 tumors and an unexplained uneven
      distribution of cases in southeast Germany.
AB  - BACKGROUND: Atypical fibroxanthoma is a rare mesenchymal tumor of the head and
      neck region. METHODS: We analyzed the files of 3 large dermatology hospitals from
      the years 2001 to 2013 in southeast Germany. RESULTS: We identified 53 patients
      (56 tumors) with a male predominance. The mean age was 78.0 years +/- 8.3 years.
      Mohs surgery was performed in all cases resulting in complete remission in 45
      patients. Five patients had a relapse within 2 years, and 4 developed metastases.
      None of the tumors with a safety margin of >=2 cm relapsed. The majority of cases
      were found in the Dresden region. CONCLUSION: Atypical fibroxanthoma demonstrates
      an uneven geographic distribution in southeast Germany that demands further
      investigations. Mohs surgery with >=2 cm safety margins is the treatment of
      choice. A regular follow-up is recommended.

PMID- 24946736
TI  - Analysis of phytoplasma-responsive sRNAs provide insight into the pathogenic
      mechanisms of mulberry yellow dwarf disease.
AB  - The yellow dwarf disease associated with phytoplasmas is one of the most
      devastating diseases of mulberry and the pathogenesis involved in the disease is
      poorly understood. To analyze the molecular mechanisms mediating gene expression
      in mulberry-phytoplasma interaction, the comprehensive sRNA changes of mulberry
      leaf in response to phytoplasma-infection were examined. A total of 164 conserved
      miRNAs and 23 novel miRNAs were identified, and 62 conserved miRNAs and 13 novel
      miRNAs were found to be involved in the response to phytoplasma-infection.
      Meanwhile, target genes of the responsive miRNAs were identified by sequencing of
      the degradome library. In addition, the endogenous siRNAs were sequenced, and
      their expression profiles were characterized. Interestingly, we found that
      phytoplasma infection induced the accumulation of mul-miR393-5p which was
      resulted from the increased transcription of MulMIR393A, and mul-miR393-5p most
      likely initiate the biogenesis of siRNAs from TIR1 transcript. Based on the
      results, we can conclude that phytoplasma-responsive sRNAs modulate multiple
      hormone pathways and play crucial roles in the regulation of development and
      metabolism. These responsive sRNAs may work cooperatively in the response to
      phytoplasma-infection and be responsible for some symptoms in the infected
      plants. 

PMID- 24946738
TI  - Phosphorylated ubiquitin: a new shade of PINK1 in Parkin activation.
AB  - The Parkinson's disease (PD)-associated proteins, Parkin and PINK1, together
      comprise a mitochondrial quality control pathway that promotes neuronal survival
      through autophagy of damaged mitochondria. Three recent studies have found that
      Parkin recruitment to mitochondria and ubiquitin ligase activity is controlled by
      the phosphorylation of ubiquitin by PINK1. 

PMID- 24946739
TI  - piRNAs, master regulators of gene expression.
AB  - Piwi-interacting RNAs (piRNAs) have a major function in the repression of
      transposable elements in the germline; in addition, they have been proposed to
      regulate gene expression. A recent study in Cell Research reveals a general role
      for piRNAs in the massive mRNA decay during mouse spermiogenesis, reinforcing
      this emerging function of piRNAs. 

PMID- 24946740
TI  - Pain-induced skin autoimmunity.
AB  - A recent paper published in Nature reports sensory nerve fibers in the skin that
      give local immune cells important instructions for the organization of an immune
      response; in this particular case the cooperation between the nervous and immune
      systems had disastrous consequences, namely an auto-destruction of the skin. 

PMID- 24946741
TI  - Treating sleeve gastrectomy leak with endoscopic stenting: the Kuwaiti experience
      and review of recent literature.
AB  - BACKGROUND: Obesity today is a leading cause of global morbidity and mortality,
      and bariatric surgeries such as laparoscopic sleeve gastrectomy (LSG) are
      increasingly playing a key role in its management. Such operations, however,
      carry many difficult and sometimes fatal complications, including leaks. This
      study aims at evaluating the effectiveness of endoscopic stenting in treating
      gastric leaks post-LSG. METHODS: A retrospective study was conducted to the
      patients who were admitted with post-LSG gastric leak at Al-Amiri Hospital Kuwait
      from October 2008 to December 2012 and were subsequently treated with stenting.
      The patients were stented endoscopically with self-expandable metal stent (SEMS),
      and a self-expandable plastic stent (SEPS) was used to facilitate stent removal.
      RESULTS: A total of 17 patients with post-LSG leaks underwent endoscopic
      stenting. The median age was 34 years (range 19-56), 53% of the patients were
      male, and mean body mass index (BMI) was 43 kg/m(2). The median duration of SEMS
      placement per patient was 42 days (range 28-84). The SEPS-assisted retrieval
      process took a median duration of 11 days (range 14-35). Successful treatment of
      gastric leak was evident in 13 (76%) patients, as evident by gastrografin swallow
      1 week after stent removal. In addition, a shorter duration between the LSG and
      the time of stent placement was associated with a higher success rate of leak
      seal. CONCLUSIONS: The use of SEMS appears to be a safe and effective method in
      the treatment of post-LSG leaks, with a success rate of 76%. The time frame of
      intervention after surgery is critical, as earlier stent placement is associated
      with favorable outcomes. Finally, SEPS is often required to facilitate SEMS
      removal, and further modification of stents and its delivery system may improve
      results.

PMID- 24946742
TI  - Proficiency training on a virtual reality robotic surgical skills curriculum.
AB  - INTRODUCTION: The clinical application of robotic surgery is increasing. The
      skills necessary to perform robotic surgery are unique from those required in
      open and laparoscopic surgery. A validated laparoscopic surgical skills
      curriculum (Fundamentals of Laparoscopic Surgery or FLSTM) has transformed the
      way surgeons acquire laparoscopic skills. There is a need for a similar skills
      training and assessment tool for robotic surgery. Our research group previously
      developed and validated a robotic training curriculum in a virtual reality (VR)
      simulator. We hypothesized that novice robotic surgeons could achieve proficiency
      levels defined by more experienced robotic surgeons on the VR robotic curriculum,
      and that this would result in improved performance on the actual daVinci Surgical
      SystemTM. METHODS: 25 medical students with no prior robotic surgery experience
      were recruited. Prior to VR training, subjects performed 2 FLS tasks 3 times each
      (Peg Transfer, Intracorporeal Knot Tying) using the daVinci Surgical SystemTM
      docked to a video trainer box. Task performance for the FLS tasks was scored
      objectively. Subjects then practiced on the VR simulator (daVinci Skills
      Simulator) until proficiency levels on all 5 tasks were achieved before
      completing a post-training assessment of the 2 FLS tasks on the daVinci Surgical
      SystemTM in the video trainer box. RESULTS: All subjects to complete the study (1
      dropped out) reached proficiency levels on all VR tasks in an average of 71 (+/-
      21.7) attempts, accumulating 164.3 (+/- 55.7) minutes of console training time.
      There was a significant improvement in performance on the robotic FLS tasks
      following completion of the VR training curriculum. CONCLUSIONS: Novice robotic
      surgeons are able to attain proficiency levels on a VR simulator. This leads to
      improved performance in the daVinci surgical platform on simulated tasks.
      Training to proficiency on a VR robotic surgery simulator is an efficient and
      viable method for acquiring robotic surgical skills.

PMID- 24946744
TI  - Use of oral anticoagulants and risk of prostate cancer: a population-based case
      control study in Montreal, Canada.
AB  - PURPOSE: A few recent epidemiological observations suggest that anticoagulant
      medications may protect against prostate cancer development. Most studies have
      been small or subjected to methodological issues, including potential
      confounding. We provide here new evidence on this association in the context of a
      population-based case-control study of prostate cancer conducted in Montreal,
      Canada. METHODS: Cases were 1,588 men with incident prostate cancer, aged <=75
      years, diagnosed across French hospitals in the Montreal area between 2005 and
      2009. Concurrently, 1,618 population controls from the same residential area and
      age distribution (+/-5 years) were randomly selected from the electoral list of
      French-speaking men. In-person interviews elicited information on socio
      demographic, lifestyle and environmental factors, along with a detailed medical
      history. Unconditional logistic regression was used to assess the association
      between lifetime use of anticoagulants and prostate cancer risk. RESULTS: 102
      subjects (2.6 % of cases and 3.7 % of controls) reported a history of oral
      anticoagulant therapy. After controlling for age, ancestry, education, family
      history of prostate cancer, prostate cancer screening frequency, diabetes, body
      mass index and statin use, ever use of oral anticoagulants showed a weak inverse,
      non-statistically significant association with prostate cancer (odds ratio 0.76,
      95% confidence interval 0.50-1.16). Similar results were observed in analyses
      considering duration of use or indication for use, restricted to subjects
      recently screened or stratified by cancer aggressiveness. CONCLUSIONS: Our
      findings provide weak support for a protective effect of oral anticoagulant
      therapy against prostate cancer. Further confirmation is required, especially in
      light of potential bleeding complications associated with anticoagulants.

PMID- 24946743
TI  - Is obesity associated with colorectal cancer screening for African American and
      Latino individuals in the context of patient navigation?
AB  - PURPOSE: The association between excess body weight and colorectal cancer
      screening is not well established. The purpose of this analysis was to explore,
      in the context of patients receiving navigation, whether obesity influences
      receipt of screening colonoscopy among lower-income Latinos and African
      Americans. METHODS: This sub-analysis was conducted among Latinos and African
      American participants who received patient navigation and had complete body mass
      index (BMI) data (n = 520). Cross-sectional survey data were collected at
      baseline among individuals 50 years and older who were referred by their primary
      care providers for a colonoscopy at Mount Sinai's Primary Care Clinic. BMI was
      based on height and weight data from chart review at baseline, and colonoscopy
      completion status was collected at 1 year post-baseline. RESULTS: The mean BMI of
      the sample was 31.17 kg/m(2), with over half (53 %) of the sample categorized as
      obese. Rates of colonoscopy screening were high (~80 %), regardless of weight
      status. Adjusting for age, gender, race/ethnicity, family history of colorectal
      cancer, smoking status, comorbid conditions, income, marital status, insurance,
      and education, obesity status was not significantly associated with screening
      behavior among the entire sample (adjusted OR 0.81, CI 0.49-1.32, p = 0.39) or
      among stratified race/ethnicity and gender groups. CONCLUSIONS: These findings
      suggest that obesity may not negatively influence receipt of colonoscopy
      screening in the context of patient navigation among minority participants.
      Further studies are needed to determine whether this finding will be observed in
      other populations, with and without the assistance of a patient navigator.

PMID- 24946746
TI  - The devil is in the details.

PMID- 24946748
TI  - Defining attraction and aggregation pheromones: teleological versus functional
      perspectives.

PMID- 24946747
TI  - Allelopathy - the solution is indirect.

PMID- 24946749
TI  - Metastatic osteosarcoma to the interventricular septum: an unusual presentation
      in a child.
AB  - Whereas primary cardiac tumors are reported in only 0.17 % of pediatric patients,
      malignant cardiac tumors are even less common in children. This report presents a
      10-year-old child with relapsed osteosarcoma manifesting as metastatic lesions to
      the interventricular septum.

PMID- 24946750
TI  - Inhibition of neuroinflammation and mitochondrial dysfunctions by carbenoxolone
      in the rotenone model of Parkinson's disease.
AB  - alpha-Synuclein aggregation contributes to the Parkinson's disease (PD) pathology
      in multiple ways-the two most important being the activation of neuroinflammation
      and mitochondrial dysfunction. Our recent studies have shown the beneficial
      effects of a heat shock protein (HSP) inducer, carbenoxolone (Cbx), in reducing
      the aggregation of alpha-synuclein in a rotenone-based rat model of PD. The
      present study was designed to explore its ability to attenuate the alpha
      synuclein-mediated alterations in neuroinflammation and mitochondrial functions.
      The PD model was generated by the rotenone administration (2 mg/kg b.wt.) to the
      male SD rats for a period of 5 weeks. Cbx (20 mg/kg b.wt.) co-administration was
      seen to reduce the activation of astrocytes incited by rotenone. Subsequently,
      the release of pro-inflammatory cytokines TNF-alpha, IL-6, and IL-1beta was
      inhibited. Further, the expression level of various inflammatory mediators such
      as COX-2, iNOS, and NF-kappaB was also reduced following Cbx co-treatment. Cbx
      was also shown to reduce the rotenone-induced decline in activity of
      mitochondrial complexes-I, -II, and -IV. Protection of mitochondrial functions
      and reduction in neuroinflammation lead to the lesser production of ROS and
      subsequently reduced oxidative stress. This was reflected by the increase in both
      the cytosolic and mitochondrial GSH levels as well as SOD activity during Cbx co
      treatment. Thus, Cbx reduces the inflammatory response and improves the
      mitochondrial dysfunctions by reducing alpha-synuclein aggregation. In addition,
      it also reduces the associated oxidative stress. Due to its ability to target the
      multiple pathways implicated in the PD, Cbx can serve as a highly beneficial
      prophylactic agent.

PMID- 24946751
TI  - Inhibition of IkappaB kinase (IKK) protects against peripheral nerve dysfunction
      of experimental diabetes.
AB  - Nuclear factor-kappaB (NF-kappaB) has been reported as a critical component of
      signalling mechanisms involved in the pathogenesis of a number of inflammatory
      conditions. Previous reports have shown that anti-inflammatory agents have a
      protective role in experimental diabetic neuropathy. Here, we assessed whether
      the inhibition of NF-kappaB cascade via IkappaB kinase (IKK) exerts any
      neuroprotective effect in experimental diabetic neuropathy. IKK inhibitor SC-514
      (1 and 3 mg/kg) was administered daily for 2 weeks starting after 6 weeks of
      streptozotocin-induced diabetes. Nerve conduction and blood flow were determined
      by Powerlab and LASER Doppler system, respectively. We evaluated the changes in
      NF-kappaB, iNOS, and COX-2 expression by Western blotting in sciatic nerve. We
      found that IKK inhibition with SC-514 increased nerve blood flow and conduction
      velocity and improved pain threshold in diabetic animals. SC-514 also reduced the
      expression of NF-kappaB and phosphorylation of IKKbeta in the sciatic nerve.
      Treatment with SC-514 reduced the elevated levels of pro-inflammatory cytokines
      (TNF-alpha and IL-6), iNOS, and COX-2. SC-514 reduces the expression of NF-kappaB
      and its downstream inflammatory components which may be involved in the
      improvement in nerve functions and pain perception in diabetic neuropathy. From
      the data of the present study, we suggest that diminution in IKK can be exploited
      as a drug target to significantly reduce the development of long-term
      complications of diabetes, particularly neuropathy.

PMID- 24946753
TI  - Current transport in graphene/AlGaN/GaN vertical heterostructures probed at
      nanoscale.
AB  - Vertical heterostructures combining two or more graphene (Gr) layers separated by
      ultra-thin insulating or semiconductor barriers represent very promising systems
      for next generation electronics devices, due to the combination of high speed
      operation with wide-range current modulation by a gate bias. They are based on
      the specific mechanisms of current transport between two-dimensional-electron
      gases (2DEGs) in close proximity. In this context, vertical devices formed by Gr
      and semiconductor heterostructures hosting an "ordinary" 2DEG can be also very
      interesting. In this work, we investigated the vertical current transport in
      Gr/Al(0.25)Ga(0.75)N/GaN heterostructures, where Gr is separated from a high
      density 2DEG by a ~ 24 nm thick AlGaN barrier layer. The current transport from
      Gr to the buried 2DEG was characterized at nanoscale using conductive atomic
      force microscopy (CAFM) and scanning capacitance microscopy (SCM). From these
      analyses, performed both on Gr/AlGaN/GaN and on AlGaN/GaN reference samples using
      AFM tips with different metal coatings, the Gr/AlGaN Schottky barrier height PhiB
      and its lateral uniformity were evaluated, as well as the variation of the
      carrier densities of graphene (ngr) and AlGaN/GaN 2DEG (ns) as a function of the
      applied bias. A low Schottky barrier (~ 0.40 eV) with excellent spatial
      uniformity was found at the Gr/AlGaN interface, i.e., lower compared to the
      measured values for metal/AlGaN contacts, which range from ~ 0.6 to ~ 1.1 eV
      depending on the metal workfunction. The electrical behavior of the Gr/AlGaN
      contact has been explained by Gr interaction with AlGaN donor-like surface states
      located in close proximity, which are also responsible of high n-type Gr doping
      (~ 1.3 * 10(13) cm(-2)). An effective modulation of ns by the Gr Schottky contact
      was demonstrated by capacitance analysis under reverse bias. From this basic
      understanding of transport properties in Gr/AlGaN/GaN heterostructures, novel
      vertical field effect transistor concepts with high operating speed and
      I(on)/I(off) ratio can be envisaged.

PMID- 24946752
TI  - On conductivity, permittivity, apparent diffusion coefficient, and their
      usefulness as cancer markers at MRI frequencies.
AB  - PURPOSE: To investigate the permittivity and conductivity of cancerous and normal
      tissues, their correlation to the apparent diffusion coefficient (ADC), and the
      specificity that they could add to cancer detection. THEORY: Breast and prostate
      carcinomas were induced in rats. Conductivity and permittivity measurements were
      performed in the anesthetized animals using a dielectric probe and an impedance
      analyzer between 50 and 270 MHz. The correlations between ADCs (measured at 128
      MHz) and conductivity values were investigated. Frequency-dependent discriminant
      functions were computed to assess the value that each parameter adds to cancer
      detection. METHODS: Tumors exhibited higher permittivity than muscle tissue by
      27%/12%/5% at 64/128/270MHz. Frequency independent, 15-20% higher conductivity
      was also noted in tumors compared to muscle tissue over the same frequency range.
      Strong negative correlation was observed between tissue conductivity and ADC.
      Whereas permittivity had the strongest discriminatory power at 64 MHz, it became
      comparable to ADC at 128 MHz and less important than ADC at 270 MHz. CONCLUSION:
      Conductivity measurements offered limited advantages in separating cancer from
      normal tissue beyond what ADC already provided; conversely, permittivity added
      separation power when added to the discriminant function. The moderately high
      cancerous tissue permittivity and conductivity impose strong constraints on the
      capability of MRI-based tissue electrical property measurements.

PMID- 24946754
TI  - The distinct abilities of tube-formation and migration between brain and spinal
      cord microvascular pericytes in rats.
AB  - Pericytes are contractile cells that wrap around the endothelial cells of
      capillaries throughout the body. They play an important role in regulating the
      blood brain barrier (BBB) and blood spinal cord barrier (BSCB). The differences
      between brain and spinal cord microvascular endothelial cells have been
      investigated. However, no report has elucidated the similarities and differences
      between brain microvascular pericytes (BMPs) and spinal cord microvascular
      pericytes (SCMPs) in vitro. The similarities were found between the two types of
      pericytes not only in the proliferation ability but also in the expression of
      toll like receptor 4. On the other hand, BMPs showed more than 2 fold in tubular
      length formation compared with SCMPs. The number of migratory SCMPs was larger
      than that of migratory BMPs. The expressions of connexin 43 and vascular
      endothelial growth factor (VEGF) in BMPs were increased compared with those in
      SCMPs, while SCMPs expressed more desmin and N-cadherin than BMPs. The abilities
      of tube-formation and migration between BMPs and SCMPs were markedly different,
      which might be mediated by VEGF, connexin 43, N-cadherin and desmin. These
      distinguishing features may reflect the more widespread differences between the
      BBB and BSCB which directly impact pathophysiological processes in various major
      diseases.

PMID- 24946755
TI  - Impact of touch preparations on core needle biopsies.
AB  - BACKGROUND: Touch preparations (TPs) can be performed for on-site adequacy
      assessment of core needle biopsies (CNBs). Although TPs can play a role in
      decreasing the number of nondiagnostic core biopsies, the impact of TPs on CNB
      has not been extensively evaluated. METHODS: Computerized tomography-guided CNBs
      performed in a tertiary cancer center were retrospectively identified. On-site
      adequacy assessment was performed in all cases. The matching TPs and CNBs were
      evaluated for diagnostic accuracy of the TP. The relation between the site of
      biopsy and the cellularity of the CNB was also analyzed. RESULTS: A total of 1100
      CNB cases with associated TPs were identified over a 6-month period. Eighty-four
      cases (8%) showed marked differences in cellularity between CNB and TP, and 43 of
      these 84 cases (4.3%) showed the presence of diagnostic cells in either CNB or
      TP, but not in both. Lung was the biopsy site where CNB was most affected by loss
      of diagnostic cells. CONCLUSIONS: TP and CNB findings must be integrated to
      prevent a misdiagnosis. Lung CNBs were more frequently affected by performing
      TPs.

PMID- 24946756
TI  - Theoretical treatment of one electron redox transformation of a small molecule
      using f-element complexes.
AB  - The theoretical treatment of single electron transfer (SET) of the redox
      chemistry mediated by f-element complexes is reviewed and summarized. The
      different computational strategies to account for the SET energy are presented
      and commented on the basis of the subsequent mechanistic investigation. Moreover,
      the mechanistic investigation of the subsequent reactivity, mainly in the field
      of heteroallene activation, using DFT-based approaches is also summarized. All
      reported reactivities are found to involve formation of bimetallic species and
      share in common the formation of the same key intermediate in which the substrate
      is doubly reduced and stabilized by two oxidized metal centers. Modern
      computational methods are found to efficiently account for such reactivity. 

PMID- 24946765
TI  - Asymmetric alkene halogenation.

PMID- 24946761
TI  - A neurocentric perspective on glioma invasion.
AB  - Malignant gliomas are devastating tumours that frequently kill patients within 1
      year of diagnosis. The major obstacle to a cure is diffuse invasion, which
      enables tumours to escape complete surgical resection and chemo- and radiation
      therapy. Gliomas use the same tortuous extracellular routes of migration that are
      travelled by immature neurons and stem cells, frequently using blood vessels as
      guides. They repurpose ion channels to dynamically adjust their cell volume to
      accommodate to narrow spaces and breach the blood-brain barrier through
      disruption of astrocytic endfeet, which envelop blood vessels. The unique biology
      of glioma invasion provides hitherto unexplored brain-specific therapeutic
      targets for this devastating disease. 

PMID- 24946762
TI  - Is the din really harmless? Long-term effects of non-traumatic noise on the adult
      auditory system.
AB  - People are increasingly being exposed to environmental noise from traffic, media
      and other sources that falls within and outside legal limits. Although such
      environmental noise is known to cause stress in the auditory system, it is still
      generally considered to be harmless. This complacency may be misplaced: even in
      the absence of cochlear damage, new findings suggest that environmental noise may
      progressively degrade hearing through alterations in the way sound is represented
      in the adult auditory cortex. 

PMID- 24946763
TI  - HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are
      targets of Bozepinib small compound.
AB  - Identification of novel anticancer drugs presenting more than one molecular
      target and efficacy against cancer stem-like cells (CSCs) subpopulations
      represents a therapeutic need to combat the resistance and the high risk of
      relapse in patients. In the present work we show how Bozepinib [(RS)-2,6-dichloro
      9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H
      purine], a small anti-tumor compound, demonstrated selectivity on cancer cells
      and showed an inhibitory effect over kinases involved in carcinogenesis,
      proliferation and angiogenesis. The cytotoxic effects of Bozepinib were observed
      in both breast and colon cancer cells expressing different receptor patterns.
      Bozepinib inhibited HER-2 signaling pathway and JNK and ERKs kinases. In
      addition, Bozepinib has an inhibitory effect on AKT and VEGF together with anti
      angiogenic and anti-migratory activities. Moreover, the modulation of pathways
      involved in tumorigenesis by Bozepinib was also evident in microarrays analysis.
      Interestingly, Bozepinib inhibited both mamo- and colono-spheres formation and
      eliminated ALDH+ CSCs subpopulations at a low micromolar range similar to
      Salinomycin. Bozepinib induced the down-regulation of c-MYC, beta-CATENIN and
      SOX2 proteins and the up-regulation of the GLI-3 hedgehog-signaling repressor.
      Finally, Bozepinib shows in vivo anti-tumor and anti-metastatic efficacy in
      xenotransplanted nude mice without presenting sub-acute toxicity. These findings
      support further studies on the therapeutic potential of Bozepinib in cancer
      patients. 

PMID- 24946770
TI  - Neutral lateral fingertip-to-floor distance can be derived from height.

PMID- 24946772
TI  - An integrated approach to energy recovery from biomass and waste: Anaerobic
      digestion-gasification-water treatment.
AB  - The article investigates the performance of an integrated system for the energy
      recovery from biomass and waste based on anaerobic digestion, gasification and
      water treatment. In the proposed system, the organic fraction of waste of the
      digestible biomass is fed into an anaerobic digester, while a part of the
      combustible fraction of the municipal solid waste is gasified. Thus, the obtained
      biogas and syngas are used as a fuel for running a cogeneration system based on
      an internal combustion engine to produce electric and thermal power. The waste
      water produced by the integrated plant is recovered by means of both forward and
      inverse osmosis. The different processes, as well as the main components of the
      system, are modelled by means of a lumped and distributed parameter approach and
      the main outputs of the integrated plant such as the electric and thermal power
      and the amount of purified water are calculated. Finally, the implementation of
      the proposed system is evaluated for urban areas with a different number of
      inhabitants and the relating performance is estimated in terms of the main
      outputs of the system. 

PMID- 24946769
TI  - Increased Excitability of Both Principal Neurons and Interneurons during
      Associative Learning.
AB  - In this review, we highlight several studies indicating that the modulation of
      intrinsic neuronal excitability is key for successful memory formation.
      Specifically, we will focus our discussion on our hypothesis that the postburst
      afterhyperpolarization (a key regulator of intrinsic excitability) is an
      essential cellular mechanism used by both principal and inhibitory neurons to
      change their neuronal activity as memory is formed. In addition, we propose that
      these intrinsic excitability changes occur first in principal neurons, followed
      by changes in inhibitory neurons, thus maintaining the balance of network
      activity among neurons for successful encoding and readout of memory. 

PMID- 24946771
TI  - Dentin-like tissue formation and biomineralization by multicellular human pulp
      cell spheres in vitro.
AB  - INTRODUCTION: Maintaining or regenerating a vital pulp is a preferable goal in
      current endodontic research. In this study, human dental pulp cell aggregates
      (spheres) were applied onto bovine and human root canal models to evaluate their
      potential use as pre-differentiated tissue units for dental pulp tissue
      regeneration. METHODS: Human dental pulp cells (DPC) were derived from wisdom
      teeth, cultivated into three-dimensional cell spheres and seeded onto bovine and
      into human root canals. Sphere formation, tissue-like and mineralization
      properties as well as growth behavior of cells on dentin structure were evaluated
      by light microscopy (LM), confocal laser scanning microscopy (CLSM), scanning
      electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX).
      RESULTS: Spheres and outgrown cells showed tissue-like properties, the ability to
      merge with other cell spheres and extra cellular matrix formation; CLSM
      investigation revealed a dense network of actin and focal adhesion contacts (FAC)
      inside the spheres and a pronounced actin structure of cells outgrown from the
      spheres. A dentin-structure-orientated migration of the cells was shown by SEM
      investigation. Besides the direct extension of the cells into dentinal tubules,
      the coverage of the tubular walls with cell matrix was detected. Moreover, an
      emulation of dentin-like structures with tubuli-like and biomineral formation was
      detected by SEM- and EDX-investigation. CONCLUSIONS: The results of the present
      study show tissue-like behavior, the replication of tubular structures and the
      mineralization of human dental pulp spheres when colonized on root dentin. The
      application of cells in form of pulp spheres on root dentin reveals their
      beneficial potential for dental tissue regeneration.

PMID- 24946773
TI  - Increased prevalence of ECG markers for sudden cardiac arrest in refractory
      epilepsy.
AB  - BACKGROUND AND AIM: People with epilepsy are at increased risk of sudden cardiac
      arrest (SCA) due to ECG-confirmed ventricular tachycardia/fibrillation, as seen
      in a community-based study. We aimed to determine whether ECG-risk markers of SCA
      are more prevalent in people with epilepsy. METHODS: In a cross-sectional,
      retrospective study, we analysed the ECG recordings of 185 people with refractory
      epilepsy and 178 controls without epilepsy. Data on epilepsy characteristics,
      cardiac comorbidity, and drug use were collected, and general ECG variables
      (heart rate (HR), PQ and QRS intervals) assessed. We analysed ECGs for three
      markers of SCA risk: severe QTc prolongation (male >450 ms, female >470 ms),
      Brugada ECG pattern, and early repolarisation pattern (ERP). Multivariate
      regression models were used to analyse differences between groups, and to
      identify associated clinical and epilepsy-related characteristics. RESULTS:
      People with epilepsy had higher HR (71 vs 62 bpm, p<0.001) and a longer PQ
      interval (162.8 vs 152.6 ms, p=0.001). Severe QTc prolongation and ERP were more
      prevalent in people with epilepsy (QTc prolongation: 5% vs 0%; p=0.002; ERP: 34%
      vs 13%, p<0.001), while the Brugada ECG pattern was equally frequent in both
      groups (2% vs 1%, p>0.999). After adjustment for covariates, epilepsy remained
      associated with ERP (ORadj 2.4, 95% CI 1.1 to 5.5) and severe QTc prolongation
      (ORadj 9.9, 95% CI 1.1 to 1317.7). CONCLUSIONS: ERP and severe QTc prolongation
      appear to be more prevalent in people with refractory epilepsy. Future studies
      must determine whether this contributes to increased SCA risk in people with
      epilepsy.

PMID- 24946774
TI  - Automatic tracking of cells for video microscopy in patch clamp experiments.
AB  - BACKGROUND: Visualisation of neurons labeled with fluorescent proteins or
      compounds generally require exposure to intense light for a relatively long
      period of time, often leading to bleaching of the fluorescent probe and
      photodamage of the tissue. Here we created a technique to drastically shorten
      light exposure and improve the targeting of fluorescent labeled cells that is
      specially useful for patch-clamp recordings. We applied image tracking and mask
      overlay to reduce the time of fluorescence exposure and minimise mistakes when
      identifying neurons. METHODS: Neurons are first identified according to visual
      criteria (e.g. fluorescence protein expression, shape, viability etc.) and a
      transmission microscopy image Differential Interference Contrast (DIC) or Dodt
      contrast containing the cell used as a reference for the tracking algorithm. A
      fluorescence image can also be acquired later to be used as a mask (that can be
      overlaid on the target during live transmission video). As patch-clamp
      experiments require translating the microscope stage, we used pattern matching to
      track reference neurons in order to move the fluorescence mask to match the new
      position of the objective in relation to the sample. For the image processing we
      used the Open Source Computer Vision (OpenCV) library, including the Speeded-Up
      Robust Features (SURF) for tracking cells. The dataset of images (n = 720) was
      analyzed under normal conditions of acquisition and with influence of noise
      (defocusing and brightness). RESULTS: We validated the method in dissociated
      neuronal cultures and fresh brain slices expressing Enhanced Yellow Fluorescent
      Protein (eYFP) or Tandem Dimer Tomato (tdTomato) proteins, which considerably
      decreased the exposure to fluorescence excitation, thereby minimising
      photodamage. We also show that the neuron tracking can be used in differential
      interference contrast or Dodt contrast microscopy. CONCLUSION: The techniques of
      digital image processing used in this work are an important addition to the set
      of microscopy tools used in modern electrophysiology, specially in experiments
      with neuron cultures and brain slices.

PMID- 24946777
TI  - Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in
      patients with circulatory shock.
AB  - INTRODUCTION: Recent clinical studies have shown a relationship between
      abnormalities in peripheral perfusion and unfavorable outcome in patients with
      circulatory shock. Nitroglycerin is effective in restoring alterations in
      microcirculatory blood flow. The aim of this study was to investigate whether
      nitroglycerin could correct the parameters of abnormal peripheral circulation in
      resuscitated circulatory shock patients. METHODS: This interventional study
      recruited patients who had circulatory shock and who persisted with abnormal
      peripheral perfusion despite normalization of global hemodynamic parameters.
      Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour)
      each 15 minutes until an improvement in peripheral perfusion was observed.
      Peripheral circulation parameters included capillary refill time (CRT), skin
      temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen
      saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were
      performed before, at the maximum dose, and after cessation of nitroglycerin
      infusion. Data were analyzed by using linear model for repeated measurements and
      are presented as mean (standard error). RESULTS: Of the 15 patients included,
      four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In
      all patients, nitroglycerin infusion resulted in significant changes in CRT,
      Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4
      (0.6) seconds to 4.8 (0.3) seconds (P < 0.05), from 3.3  degrees C (0.7  degrees
      C) to 0.7  degrees C (0.6  degrees C) (P < 0.05), and from [log] -0.5% (0.2%) to
      0.7% (0.1%) (P < 0.05), respectively. Similar changes in StO2 and RincStO2 were
      observed: from 75% (3.4%) to 84% (2.7%) (P < 0.05) and 1.9%/second (0.08%/second)
      to 2.8%/second (0.05%/second) (P < 0.05), respectively. The magnitude of changes
      in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%,
      respectively (P < 0.05). CONCLUSIONS: Dose-dependent infusion of nitroglycerin
      reverted abnormal peripheral perfusion and poor tissue oxygenation in patients
      following circulatory shock resuscitation. Individual requirements of
      nitroglycerin dose to improve peripheral circulation vary between patients. A
      simple and fast physical examination of peripheral circulation at the bedside can
      be used to titrate nitroglycerin infusion.

PMID- 24946776
TI  - Sunlight exposure and cardiovascular risk factors in the REGARDS study: a cross
      sectional split-sample analysis.
AB  - BACKGROUND: Previous research has suggested that vitamin D and sunlight are
      related to cardiovascular outcomes, but associations between sunlight and risk
      factors have not been investigated. We examined whether increased sunlight
      exposure was related to improved cardiovascular risk factor status. METHODS:
      Residential histories merged with satellite, ground monitor, and model reanalysis
      data were used to determine previous-year sunlight radiation exposure for 17,773
      black and white participants aged 45+ from the US. Exploratory and confirmatory
      analyses were performed by randomly dividing the sample into halves. Logistic
      regression models were used to examine relationships with cardiovascular risk
      factors. RESULTS: The lowest, compared to the highest quartile of insolation
      exposure was associated with lower high-density lipoprotein levels in adjusted
      exploratory (-2.7 mg/dL [95% confidence interval: -4.2, -1.2]) and confirmatory (
      1.5 mg/dL [95% confidence interval: -3.0, -0.1]) models. The lowest, compared to
      the highest quartile of insolation exposure was associated with higher systolic
      blood pressure levels in unadjusted exploratory and confirmatory, as well as the
      adjusted exploratory model (2.3 mmHg [95% confidence interval: 0.8, 3.8]), but
      not the adjusted confirmatory model (1.6 mg/dL [95% confidence interval: -0.5,
      3.7]). CONCLUSIONS: The results of this study suggest that lower long-term
      sunlight exposure has an association with lower high-density lipoprotein levels.
      However, all associations were weak, thus it is not known if insolation may
      affect cardiovascular outcomes through these risk factors.

PMID- 24946775
TI  - Population typing of the causal agent of cassava bacterial blight in the Eastern
      Plains of Colombia using two types of molecular markers.
AB  - BACKGROUND: Molecular typing of pathogen populations is an important tool for the
      development of effective strategies for disease control. Diverse molecular
      markers have been used to characterize populations of Xanthomonas axonopodis pv.
      manihotis (Xam), the main bacterial pathogen of cassava. Recently, diversity and
      population dynamics of Xam in the Colombian Caribbean coast were estimated using
      AFLPs, where populations were found to be dynamic, diverse and with haplotypes
      unstable across time. Aiming to examine the current state of pathogen populations
      located in the Colombian Eastern Plains, we also used AFLP markers and we
      evaluated the usefulness of Variable Number Tandem Repeats (VNTRs) as new
      molecular markers for the study of Xam populations. RESULTS: The population
      analyses showed that AFLP and VNTR provide a detailed and congruent description
      of Xam populations from the Colombian Eastern Plains. These two typing strategies
      clearly separated strains from the Colombian Eastern Plains into distinct
      populations probably because of geographical distance. Although the majority of
      analyses were congruent between typing markers, fewer VNTRs were needed to detect
      a higher number of genetic populations of the pathogen as well as a higher
      genetic flow among sampled locations than those detected by AFLPs. CONCLUSIONS:
      This study shows the advantages of VNTRs over AFLPs in the surveillance of
      pathogen populations and suggests the implementation of VNTRs in studies that
      involve large numbers of Xam isolates in order to obtain a more detailed overview
      of the pathogen to improve the strategies for disease control.

PMID- 24946779
TI  - Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid
      in breast cancer cells in vitro.
AB  - BACKGROUND: Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer
      cells. This modification of epigenetic information may be of therapeutic
      relevance in the perioperative period, because a decrease in methylation can
      reactivate tumour suppressor genes and inhibit tumour growth. The objectives of
      this study were to determine the effect of two amide local anaesthetics,
      ropivacaine and bupivacaine, on methylation in two breast cancer cell lines and
      to detect whether the combination of lidocaine with the chemotherapy agent 5-aza
      2'-deoxycytidine (DAC) would result in additive demethylating effects. METHODS:
      Breast cancer cell lines BT-20 [oestrogen receptor (ER)-negative] and MCF-7 (ER
      positive) were incubated with lidocaine, bupivacaine, and ropivacaine to assess
      demethylating properties. Then, we tested varying concentrations of lidocaine and
      DAC to assess whether their demethylating effects were additive. Cell numbers and
      global methylation status were analysed. RESULTS: Lidocaine decreased methylation
      in BT-20 and MCF-7 cells, ropivacaine decreased methylation in BT-20 cells, and
      bupivacaine had no demethylating effect. When combined, lidocaine and DAC had
      additive demethylating effects. CONCLUSIONS: At clinically relevant doses,
      lidocaine and ropivacaine exert demethylating effects on specific breast cancer
      cell lines, but bupivacaine does not. The demethylating effects of lidocaine and
      DAC are indeed additive.

PMID- 24946778
TI  - Managing malaria in the intensive care unit.
AB  - The number of people travelling to malaria-endemic countries continues to
      increase, and malaria remains the commonest cause of serious imported infection
      in non-endemic areas. Severe malaria, mostly caused by Plasmodium falciparum,
      often requires intensive care unit (ICU) admission and can be complicated by
      cerebral malaria, respiratory distress, acute kidney injury, bleeding
      complications, and co-infection. The mortality from imported malaria remains
      significant. This article reviews the manifestations, complications and
      principles of management of severe malaria as relevant to critical care
      clinicians, incorporating recent studies of anti-malarial and adjunctive
      treatment. Effective management of severe malaria includes prompt diagnosis and
      early institution of effective anti-malarial therapy, recognition of
      complications, and appropriate supportive management in an ICU. All cases should
      be discussed with a specialist unit and transfer of the patient considered. 

PMID- 24946781
TI  - A model-based information sharing protocol for profile Hidden Markov Models used
      for HIV-1 recombination detection.
AB  - BACKGROUND: In many applications, a family of nucleotide or protein sequences
      classified into several subfamilies has to be modeled. Profile Hidden Markov
      Models (pHMMs) are widely used for this task, modeling each subfamily separately
      by one pHMM. However, a major drawback of this approach is the difficulty of
      dealing with subfamilies composed of very few sequences. One of the most crucial
      bioinformatical tasks affected by the problem of small-size subfamilies is the
      subtyping of human immunodeficiency virus type 1 (HIV-1) sequences, i.e., HIV-1
      subtypes for which only a small number of sequences is known. RESULTS: To deal
      with small samples for particular subfamilies of HIV-1, we introduce a novel
      model-based information sharing protocol. It estimates the emission probabilities
      of the pHMM modeling a particular subfamily not only based on the nucleotide
      frequencies of the respective subfamily but also incorporating the nucleotide
      frequencies of all available subfamilies. To this end, the underlying
      probabilistic model mimics the pattern of commonality and variation between the
      subtypes with regards to the biological characteristics of HI viruses. In order
      to implement the proposed protocol, we make use of an existing HMM architecture
      and its associated inference engine. CONCLUSIONS: We apply the modified algorithm
      to classify HIV-1 sequence data in the form of partial HIV-1 sequences and semi
      artificial recombinants. Thereby, we demonstrate that the performance of pHMMs
      can be significantly improved by the proposed technique. Moreover, we show that
      our algorithm performs significantly better than Simplot and Bootscanning.

PMID- 24946782
TI  - Validation of the Brazilian Portuguese Version of Geriatric Anxiety Inventory-
      GAI-BR.
AB  - BACKGROUND: The Geriatric Anxiety Inventory (GAI) is a recently developed scale
      aiming to evaluate symptoms of anxiety in later life. This 20-item scale uses
      dichotomous answers highlighting non-somatic anxiety complaints of elderly
      people. The present study aimed to evaluate the psychometric properties of the
      Brazilian Portuguese version GAI (GAI-BR) in a sample from community and
      outpatient psychogeriatric clinic. METHODS: A mixed convenience sample of 72
      subjects was recruited for answering the research protocol. The interview
      procedures were structured with questionnaires about sociodemographic data,
      clinical health status, anxiety, and depression previously validated instruments,
      Mini-Mental State Examination, Mini International Neuropsychiatric Interview, and
      GAI-BR. Twenty-two percent of the sample were interviewed twice for test-retest
      reliability. For internal consistency analyses, the Cronbach's alpha test was
      applied. The Spearman correlation test was applied to evaluate the test-retest
      GAI-BR reliability. A ROC (receiver operating characteristic) curve study was
      made to estimate the GAI-BR area under curve, cut-off points, sensitivity, and
      specificity for the Generalized Anxiety Disorder diagnosis. RESULTS: The GAI-BR
      version showed high internal consistency (Cronbach's alpha = 0.91) and strong and
      significant test-retest reliability (rho = 0.85, p < 0.001). It also showed
      moderate and significant correlation with the Beck Anxiety Inventory (rho = 0.68,
      p < 0.001) and the State-Trait Anxiety Inventory (rho = 0.61, p < 0.001) showing
      evidence of concurrent validation. The cut-off point of 13 estimated by ROC curve
      analyses showed sensitivity of 83.3% and specificity of 84.6% to detect
      Generalized Anxiety Disorder (DSM-IV). CONCLUSION: GAI-BR has demonstrated very
      good psychometric properties and can be a reliable instrument to measure anxiety
      in Brazilian elderly people.

PMID- 24946783
TI  - "I'm a storyteller!": Exploring the benefits of TimeSlips creative expression
      program at a nursing home.
AB  - BACKGROUND: TimeSlips creative storytelling program is beneficial for persons
      with dementia and caregivers, but no studies have qualitatively explored
      participant experience. METHODS: Ten residents in a skilled nursing care unit
      participated in 2-hour-long TimeSlips sessions per week, for 6 weeks.
      Semistructured interviews of participants and staff members were conducted to
      elicit perceptions of TimeSlips. Thematic analysis was used to evaluate
      qualitative data. RESULTS: There were specific benefits for residents (increased
      creativity, improved quality of life, positively altered behavior, and
      involvement in meaningful activity), staff members (learning new practices,
      developing a deeper understanding of residents, involvement in meaningful
      activity, and thinking creatively around programmatic challenges), and the
      nursing home community (nurturing relationships and improved atmosphere).
      CONCLUSION: Involvement in TimeSlips can engender benefits for residents, staff,
      and nursing home communities. Future research is needed to quantitatively assess
      whether the benefits noted in this study can longitudinally improve quality and
      lower cost of long-term care.

PMID- 24946784
TI  - Cognitive fluctuations as a challenge for the assessment of decision-making
      capacity in patients with dementia.
AB  - Decision-making capacity (DMC) is an indispensable prerequisite for medical
      treatment choices, including consent to treatment, treatment discontinuation, and
      refusal of treatment. In patients with dementia, DMC is often affected. A
      particular challenge in assessing DMC are cognitive fluctuations that may lead to
      a fluctuation in DMC as well. Cognitive fluctuations are a diagnostic core
      feature of dementia with Lewy bodies and occur in Parkinson's and Alzheimer's
      diseases. In this article, these challenges are discussed and suggestions for
      assessing the DMC of patients with dementia with cognitive fluctuations are
      presented. 

PMID- 24946780
TI  - Genetic basis of pyrethroid resistance in a population of Anopheles arabiensis,
      the primary malaria vector in Lower Moshi, north-eastern Tanzania.
AB  - BACKGROUND: Pyrethroid resistance has been slower to emerge in Anopheles
      arabiensis than in An. gambiae s.s and An. funestus and, consequently, studies
      are only just beginning to unravel the genes involved. Permethrin resistance in
      An. arabiensis in Lower Moshi, Tanzania has been linked to elevated levels of
      both P450 monooxygenases and beta-esterases. We have conducted a gene expression
      study to identify specific genes linked with metabolic resistance in the Lower
      Moshi An. arabiensis population. METHODS: Microarray experiments employing an An.
      gambiae whole genome expression chip were performed on An. arabiensis, using
      interwoven loop designs. Permethrin-exposed survivors were compared to three
      separate unexposed mosquitoes from the same or a nearby population. A subsection
      of detoxification genes were chosen for subsequent quantitative real-time PCR
      (qRT-PCR). RESULTS: Microarray analysis revealed significant over expression of
      87 probes and under expression of 85 probes (in pairwise comparisons between
      permethrin survivors and unexposed sympatric and allopatric samples from Dar es
      Salaam (controls). For qRT-PCR we targeted over expressed ABC transporter genes
      (ABC '2060'), a glutathione-S-transferase, P450s and esterases. Design of
      efficient, specific primers was successful for ABC '2060'and two P450s (CYP6P3,
      CYP6M2). For the CYP4G16 gene, we used the primers that were previously used in a
      microarray study of An. arabiensis from Zanzibar islands. Over expression of
      CYP4G16 and ABC '2060' was detected though with contrasting patterns in pairwise
      comparisons between survivors and controls. CYP4G16 was only up regulated in
      survivors, whereas ABC '2060' was similar in survivors and controls but over
      expressed in Lower Moshi samples compared to the Dar es Salaam samples. Increased
      transcription of CYP4G16 and ABC '2060' are linked directly and indirectly
      respectively, with permethrin resistance in Lower Moshi An. arabiensis.
      CONCLUSIONS: Increased transcription of a P450 (CYP4G16) and an ABC transporter
      (ABC 2060) are linked directly and indirectly respectively, with permethrin
      resistance in Lower Moshi An. arabiensis. Our study provides replication of
      CYP4G16 as a candidate gene for pyrethroid resistance in An. arabiensis, although
      its role may not be in detoxification, and requires further investigation.

PMID- 24946785
TI  - Melatonin and melatonin agonist for delirium in the elderly patients.
AB  - The objective of this review is to summarize the available data on the use of
      melatonin and melatonin agonist for the prevention and management of delirium in
      the elderly patients from randomized controlled trials (RCTs). A systematic
      search of 5 major databases PubMed, MEDLINE, PsychINFO, Embase, and Cochrane
      Library was conducted. This search yielded a total of 2 RCTs for melatonin. One
      study compared melatonin to midazolam, clonidine, and control groups for the
      prevention and management of delirium in individuals who were pre- and posthip
      post-hip arthroplasty. The other study compared melatonin to placebo for the
      prevention of delirium in older adults admitted to an inpatient internal medicine
      service. Data from these 2 studies indicate that melatonin may have some benefit
      in the prevention and management of delirium in older adults. However, there is
      no evidence that melatonin reduces the severity of delirium or has any effect on
      behaviors or functions in these individuals. Melatonin was well tolerated in
      these 2 studies. The search for a melatonin agonist for delirium in the elderly
      patients yielded 1 study of ramelteon. In this study, ramelteon was found to be
      beneficial in preventing delirium in medically ill individuals when compared to
      placebo. Ramelteon was well tolerated in this study.

PMID- 24946787
TI  - Glycoxidation of biological macromolecules: a critical approach to halt the
      menace of glycation.
AB  - Glycation is the result of covalent bonding of a free amino group of biological
      macromolecules with a reducing sugar, which results in the formation of a Schiff
      base that undergoes rearrangement, dehydration and cyclization to form a more
      stable Amadori product. The final products of nonenzymatic glycation of
      biomacromolecules like DNA, proteins and lipids are known as advanced glycation
      end products (AGEs). AGEs may be generated rapidly or over long times stimulated
      by distinct triggering mechanisms, thereby accounting for their roles in multiple
      settings and disease states. Both Schiff base and Amadori glycation products
      generate free radicals resulting in decline of antioxidant defense mechanisms and
      can damage cellular organelles and enzymes. This critical review primarily
      focuses on the mechanistic insight of glycation and the most probable route for
      the formation of glycation products and their therapeutic interventions.
      Furthermore, the prevention of glycation reaction using therapeutic drugs such as
      metformin, pyridoxamine and aminoguanidine (AG) are discussed with special
      emphasis on the novel concept of the bioconjugation of these drugs like, AG with
      gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be
      toxic and therefore has serious health concerns, and the study warrants doing
      this novel bioconjugation of AG with GNPs. This approach might increase the
      efficacy of the AG at a reduced concentration with low or no toxicity. Using the
      concept of synthesis of GNPs with abovementioned drugs, it is assumed that
      toxicity of various drugs which are used at high doses can be minimized more
      effectively. 

PMID- 24946786
TI  - Co-morbidities are the key nominators of the health related quality of life in
      mild and moderate COPD.
AB  - BACKGROUND: Co-morbidities are common in chronic obstructive pulmonary disease
      (COPD). We assessed the contribution of common co-morbidities on health related
      quality of life (HRQoL) among COPD patients. METHODS: Using both generic (15D)
      and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital
      based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this
      observational study with inferential analysis. The prevalence of their co
      morbidities was compared with those of 5000 population controls. The patients
      represented all severity stages of COPD and the patterns of common concomitant
      disorders differed between patients. RESULTS: Co-morbidities such as psychiatric
      conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common
      among COPD patients than in age and gender matched controls. Psychiatric
      conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and
      could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR
      2.0 and 3.0) instruments. Compared to respiratory specific AQ20, generic 15D was
      more sensitive to the effects of comorbidities while AQ20 was slightly more
      sensitive for the low FEV1. FEV1 was a strong determinant of HRQoL only at more
      severe stages of disease (FEV1 < 40% of predicted). Poor HRQoL also predicted
      death during the next five years. CONCLUSIONS: The results suggest that co
      morbidities may impair HRQoL at an early stage of the disease, while bronchial
      obstruction becomes a significant determinant of HRQoL only in severe COPD.

PMID- 24946788
TI  - Mucin-type O-glycosylation is critical for vascular integrity.
AB  - Vascular endothelial cells, in addition to many other mammalian cell types,
      express proteins that are highly modified with mucin-type O-glycosylation, a
      specific type of glycosylation that begins with the addition of an N
      acetylgalactosamine moiety to serine or threonine residues within the peptide
      backbone. Recently, it has become evident that O-glycosylation governs the
      separation of blood and lymphatic vessels throughout life and plays a critical
      role in maintaining vascular integrity in specific tissues such as the brain and
      lymph node. This mini-review seeks to highlight some of these recent advances
      regarding in vivo functions of mucin-type O-glycans. 

PMID- 24946789
TI  - Enhanced proliferation and differentiation of Oct4- and Sox2-overexpressing human
      adipose tissue mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are attractive candidates for clinical repair or
      regeneration of damaged tissues. Oct4 and Sox2, which are essential transcription
      factors for pluripotency and self-renewal, are naturally expressed in MSCs at low
      levels in early passages, and their levels gradually decrease as the passage
      number increases. Therefore, to improve MSC proliferation and stemness, we
      introduced human Oct4 and Sox2 for conferring higher expansion and
      differentiation capabilities. The Oct4-IRES-Sox2 vector was transfected into
      human adipose tissue MSCs (ATMSCs) by liposomal transfection and used directly.
      Oct4 and Sox2 were successfully transfected into ATMSCs, and we confirmed
      maintenance of MSC surface markers without alterations in both red fluorescent
      protein (RFP) (control) and Oct4/Sox2-ATMSCs. Enhanced proliferative activity of
      Oct4/Sox2-ATMSCs was shown by WST-1 assay, and this result was further confirmed
      by cell counting using trypan blue exclusion for a long period. In addition, FACs
      cell cycle analysis showed that there was a reduction in the fraction of
      Oct4/Sox2-ATMSCs in G1 with a concomitant increase in the fraction of cells in S,
      compared with RFP-ATMSCs. Increased levels of cyclin D1 were also seen in
      Oct4/Sox2-ATMSCs, indicating acceleration in the transition of cells from G1 to S
      phase. Furthermore, Oct4/Sox2-overexpressing ATMSCs showed higher differentiation
      abilities for adipocytes or osteoblasts than controls. The markers of adipogenic
      or osteogenic differentiation were also upregulated by Oct4/Sox2 overexpression.
      The improvement in cell proliferation and differentiation using Oct4/Sox2
      expression in ATMSCs may be a useful method for expanding the population and
      increasing the stemness of ATMSCs. 

PMID- 24946791
TI  - Probing the solar corona with very long baseline interferometry.
AB  - Understanding and monitoring the solar corona and solar wind is important for
      many applications like telecommunications or geomagnetic studies. Coronal
      electron density models have been derived by various techniques over the last 45
      years, principally by analysing the effect of the corona on spacecraft tracking.
      Here we show that recent observational data from very long baseline
      interferometry (VLBI), a radio technique crucial for astrophysics and geodesy,
      could be used to develop electron density models of the Sun's corona. The VLBI
      results agree well with previous models from spacecraft measurements. They also
      show that the simple spherical electron density model is violated by regional
      density variations and that on average the electron density in active regions is
      about three times that of low-density regions. Unlike spacecraft tracking, a VLBI
      campaign would be possible on a regular basis and would provide highly resolved
      spatial-temporal samplings over a complete solar cycle. 

PMID- 24946793
TI  - Sensitive fluorescence-based method for the rapid determination of polysorbate-80
      content in therapeutic monoclonal antibody products.
AB  - Abstract A sensitive and effective method has been developed for the rapid
      determination of polysorbate-80 content in therapeutic monoclonal antibody (mAb)
      products. The method is based on the detection of the fluorescence emission of
      4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt (bis-ANS)
      enhanced by the presence of polysorbate-80. The developed method includes two
      approaches. One requires removal of the mAb from solution prior to analysis,
      while the other requires only simple sample dilution. The limits of detection and
      quantitation, calculated from the calibration curve generated in the absence of
      mAb-A, were 1.5 and 4.7 parts per million, respectively. Given the comparable
      linear range and linearity of the linear line between the solutions, with or
      without mAb, the limit of detection and quantitation is assumed to be similar.
      The dilution method is not only fast and simple in terms of sample preparation,
      but it is also particularly useful for analyzing the level of polysorbate-80
      contained in highly concentrated mAb products. However, given that this method
      does require availability of polysorbate-80-free materials of mAb for preparation
      of calibration standards, the protein removal method may be useful for the cases
      where appropriate protein materials for standard preparation are limited or
      unavailable.

PMID- 24946792
TI  - Short communication: serum-based assay accurately detects single nucleotide
      polymorphisms of IL28B and SOCS3 in HIV/hepatitis C virus-coinfected subjects.
AB  - Single nucleotide polymorphisms (SNPs) have become important in predicting
      treatment response to interferon containing anti-hepatitis C virus (HCV) therapy
      in HCV and HIV/HCV-infected patients. A reliable method for extracting host DNA
      from serum for genotyping assays would present a practical alternative for
      clinicians and investigators seeking to perform SNP analyses in HCV-infected
      patients, particularly in resource-limited settings. Human genomic DNA was
      extracted from peripheral blood mononuclear cells (PBMCs) and serum of 51 HIV/HCV
      coinfected patients using the QIAamp DNA Blood Mini Kit and QIAamp Min Elute
      Virus Spin Kit, respectively. Genotyping assays for the IL28B SNP (rs12979860)
      and SOCS3 SNP (rs4969170) were performed using the commercially available ABI
      Taqman allelic discrimination kit and reverse transcriptase-polymerase chain
      reaction (RT-PCR) was performed using 50 cycles. Results of the genotyping assays
      using DNA from both PBMCs and cell-free serum were determined separately and then
      analyzed for concurrence. Genotype analyses performed using DNA isolated from
      PBMCs or cell-free serum showed a 100% agreement between the IL28B genotyping
      results from the serum and PBMC isolates and 98% agreement for SOCS3 SNP. This
      novel serum-based assay to isolate DNA fragments from the serum of HIV/HCV
      coinfected subjects can accurately determine a subject's genotype for IL28B
      (rs12979860) and SOCS3 (rs4969170). This assay could be immediately valuable for
      detecting clinically relevant SNPs from serum in cases in which PBMCs are not
      available.

PMID- 24946790
TI  - Inhibitory G proteins and their receptors: emerging therapeutic targets for
      obesity and diabetes.
AB  - The worldwide prevalence of obesity is steadily increasing, nearly doubling
      between 1980 and 2008. Obesity is often associated with insulin resistance, a
      major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease
      and serious public health problem. The underlying cause of T2DM is a failure of
      the beta cells of the pancreas to continue to produce enough insulin to
      counteract insulin resistance. Most current T2DM therapeutics do not prevent
      continued loss of insulin secretion capacity, and those that do have the
      potential to preserve beta cell mass and function are not effective in all
      patients. Therefore, developing new methods for preventing and treating obesity
      and T2DM is very timely and of great significance. There is now considerable
      literature demonstrating a link between inhibitory guanine nucleotide-binding
      protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin
      responsive tissues and the pathogenesis of obesity and T2DM. These studies are
      suggesting new and emerging therapeutic targets for these conditions. In this
      review, we will discuss inhibitory G proteins and GPCRs that have primary actions
      in the beta cell and other peripheral sites as therapeutic targets for obesity
      and T2DM, improving satiety, insulin resistance and/or beta cell biology. 

PMID- 24946794
TI  - In vitro pharmaceutical characterization and statistical optimization of a novel
      topically applied instantly-soluble solid eye drop matrix.
AB  - Abstract Ocular diseases of the anterior segment of the eye are increasing and
      the development of novel drug delivery systems for improved treatment is
      necessary. The aim of this study was therefore to design and evaluate an
      instantly-soluble solid eye drop (ISED) for topical ophthalmic drug delivery of
      the model drug timolol maleate. The porous nature of the lyophilized ISED
      resulted in rapid fluid ingression, immediate hydration, and dissolution of the
      ocular matrix. The ISED was lyophilized employing hydroxypropylcellulose and
      pluronic(r) F68 as the matrix forming polymers. Polyacrylic acid sodium enhanced
      the solubility of the ISED, di-glycine, an anti-collapsing agent, while
      maltodextrin improved the matrix resilience. A statistical design was employed
      for optimizing the texture, disintegration, and the mean dissolution time
      (MDT50%) of the ISED. Results revealed that a robust rapidly disintegrating ISED
      was produced with the fastest disintegration time recorded at 0.20 s and drug
      release between 79 and 96%. In addition, improved corneal drug permeation was
      observed compared to pure timolol dispersion. The maltodextrin concentration
      significantly affected the ISED matrix resilience (p = 0.007) and pluronic F68
      had a greater impact on disintegration time (p = 0.000) and MDT (p = 0.000). The
      ISED formulation may be a promising alternative to the use of liquid eye drops
      for topical ophthalmic drug delivery.

PMID- 24946795
TI  - Permeability enhancing lipid-based co-solvent and SEDDS formulations of SQ641, an
      antimycobacterial agent.
AB  - CONTEXT: Tuberculosis (TB) is a common and often deadly infectious disease caused
      by strains of Mycobacteria. Development of new anti-tubercular drugs is essential
      to control the emergence and severity of multidrug-resistant TB. OBJECTIVE: The
      objective of this study was to develop an oral preclinical liquid formulation of
      SQ641 and to determine the permeability across rat intestinal tissue by Ussing
      chamber. METHODS: Thermal and chemical characterization of SQ641 was performed by
      differential scanning calorimetric analysis, thermogravimetric analysis and high
      performance liquid chromatography. A high throughput solubility screening
      technique was utilized to determine the solubility of SQ641 in different solvents
      and co-solvents. Several co-solvent and self-emulsifying drug delivery system
      (SEDDS) formulations were selected for Ussing chamber permeability studies.
      RESULTS AND DISCUSSION: Calculated average apparent permeability coefficients of
      SEDDS formulations of SQ641 (ranging from 0.03 * 10(-6) to 0.33 * 10(-6)) were
      found to be higher than the permeability coefficients of co-solvent formulations
      (ranging from 0.00 * 10(-6) to 0.09 * 10(-6)) and those of the neat drug SQ641 in
      buffer (0.00 * 10(-6)). CONCLUSION: SEDDS formulations with superior permeability
      characteristics may provide a useful dosage form for oral intake of anti
      tubercular drug SQ641, possibly due to the increase in solubility and immediate
      dispersion of drug.

PMID- 24946796
TI  - Influenza vaccine effectiveness: best practice and current limitations of the
      screening method and their implications for the clinic.
AB  - Is there a role for the screening method in estimating influenza vaccine
      effectiveness (VE)? The answer is yes, but the simplicity of the method used has
      raised concerns about its validity, and several cautions should be noted. The
      screening method provides an approximation of influenza VE by comparing the
      proportion of cases vaccinated (PCV) with the proportion of persons vaccinated
      (PPV) in the general population. This method has an important disadvantage: VE
      estimation could be inaccurate if the values for PCV and PPV are drawn from
      different populations, but it has an important strength, compared with other
      observational studies, in providing an early indication of VE in the field. Thus,
      when an infrastructure, such as routine surveillance, is in place to collect
      robust PCV values, and PPV can be obtained from routine vaccine uptake monitoring
      systems, the screening method can provide early estimates of influenza VE in
      target groups. 

PMID- 24946797
TI  - Connecting core percolation and controllability of complex networks.
AB  - Core percolation is a fundamental structural transition in complex networks
      related to a wide range of important problems. Recent advances have provided us
      an analytical framework of core percolation in uncorrelated random networks with
      arbitrary degree distributions. Here we apply the tools in analysis of network
      controllability. We confirm analytically that the emergence of the bifurcation in
      control coincides with the formation of the core and the structure of the core
      determines the control mode of the network. We also derive the analytical
      expression related to the controllability robustness by extending the deduction
      in core percolation. These findings help us better understand the interesting
      interplay between the structural and dynamical properties of complex networks. 

PMID- 24946798
TI  - The strength of the strongest ties in collaborative problem solving.
AB  - Complex problem solving in science, engineering, and business has become a highly
      collaborative endeavor. Teams of scientists or engineers collaborate on projects
      using their social networks to gather new ideas and feedback. Here we bridge the
      literature on team performance and information networks by studying teams'
      problem solving abilities as a function of both their within-team networks and
      their members' extended networks. We show that, while an assigned team's
      performance is strongly correlated with its networks of expressive and
      instrumental ties, only the strongest ties in both networks have an effect on
      performance. Both networks of strong ties explain more of the variance than other
      factors, such as measured or self-evaluated technical competencies, or the
      personalities of the team members. In fact, the inclusion of the network of
      strong ties renders these factors non-significant in the statistical analysis.
      Our results have consequences for the organization of teams of scientists,
      engineers, and other knowledge workers tackling today's most complex problems. 

PMID- 24946799
TI  - Effects of upper limb robot-assisted therapy on motor recovery in subacute stroke
      patients.
AB  - BACKGROUND AND PURPOSE: There is little evidence available on the use of robot
      assisted therapy in subacute stroke patients. A randomized controlled trial was
      carried out to evaluate the short-time efficacy of intensive robot-assisted
      therapy compared to usual physical therapy performed in the early phase after
      stroke onset. METHODS: Fifty-three subacute stroke patients at their first-ever
      stroke were enrolled 30 +/- 7 days after the acute event and randomized into two
      groups, both exposed to standard therapy. Additional 30 sessions of robot
      assisted therapy were provided to the Experimental Group. Additional 30 sessions
      of usual therapy were provided to the Control Group.The following impairment
      evaluations were performed at the beginning (T0), after 15 sessions (T1), and at
      the end of the treatment (T2): Fugl-Meyer Assessment Scale (FM), Modified
      Ashworth Scale-Shoulder (MAS-S), Modified Ashworth Scale-Elbow (MAS-E), Total
      Passive Range of Motion-Shoulder/Elbow (pROM), and Motricity Index (MI). RESULTS:
      Evidence of significant improvements in MAS-S (p = 0.004), MAS-E (p = 0.018) and
      pROM (p < 0.0001) was found in the Experimental Group. Significant improvement
      was demonstrated in both Experimental and Control Group in FM (EG: p < 0.0001,
      CG: p < 0.0001) and MI (EG: p < 0.0001, CG: p < 0.0001), with an higher
      improvement in the Experimental Group. CONCLUSIONS: Robot-assisted upper limb
      rehabilitation treatment can contribute to increasing motor recovery in subacute
      stroke patients. Focusing on the early phase of stroke recovery has a high
      potential impact in clinical practice.

PMID- 24946800
TI  - The ColRS signal transduction system responds to the excess of external zinc,
      iron, manganese, and cadmium.
AB  - BACKGROUND: The ColRS two-component system has been shown to contribute to the
      membrane functionality and stress tolerance of Pseudomonas putida as well as to
      the virulence of Pseudomonas aeruginosa and plant pathogenic Xanthomonas species.
      However, the conditions activating the ColRS pathway and the signal(s) sensed by
      ColS have remained unknown. Here we aimed to analyze the role of the ColRS system
      in metal tolerance of P. putida and to test whether ColS can respond to metal
      excess. RESULTS: We show that the ColRS system is necessary for P. putida to
      tolerate the excess of iron and zinc, and that it also contributes to manganese
      and cadmium tolerance. Excess of iron, zinc, manganese or cadmium activates ColRS
      signaling and as a result modifies the expression of ColR-regulated genes. Our
      data suggest that the genes in the ColR regulon are functionally redundant, as
      several loci have to be deleted to observe a significant decrease in metal
      tolerance. Site-directed mutagenesis of ColS revealed that excess of iron and,
      surprisingly, also zinc are sensed by a conserved ExxE motif in ColS's
      periplasmic domain. While ColS is able to sense different metals, it still
      discriminates between the two oxidation states of iron, specifically responding
      to ferric and not ferrous iron. We propose a signal perception model involving a
      dimeric ColS, where each monomer donates one ExxE motif for metal binding.
      CONCLUSIONS: Several transition metals are essential for living organisms in
      certain amounts, but toxic in excess. We show that ColRS is a sensor system which
      detects and responds to the excess of physiologically important metals such as
      zinc, iron and manganese. Thus, the ColRS system is an important factor for metal
      homeostasis and tolerance in P. putida.

PMID- 24946802
TI  - Alternative to faith-based science.

PMID- 24946801
TI  - Modelling environmental factors correlated with podoconiosis: a geospatial study
      of non-filarial elephantiasis.
AB  - INTRODUCTION: The precise trigger of podoconiosis - endemic non-filarial
      elephantiasis of the lower legs - is unknown. Epidemiological and ecological
      studies have linked the disease with barefoot exposure to red clay soils of
      volcanic origin. Histopathology investigations have demonstrated that silicon,
      aluminium, magnesium and iron are present in the lower limb lymph node
      macrophages of both patients and non-patients living barefoot on these clays. We
      studied the spatial variation (variations across an area) in podoconiosis
      prevalence and the associated environmental factors with a goal to better
      understanding the pathogenesis of podoconiosis. METHODS: Fieldwork was conducted
      from June 2011 to February 2013 in 12 kebeles (administrative units) in northern
      Ethiopia. Geo-located prevalence data and soil samples were collected and
      analysed along with secondary geological, topographic, meteorological and
      elevation data. Soil data were analysed for chemical composition, mineralogy and
      particle size, and were interpolated to provide spatially continuous information.
      Exploratory, spatial, univariate and multivariate regression analyses of
      podoconiosis prevalence were conducted in relation to primary (soil) and
      secondary (elevation, precipitation, and geology) covariates. RESULTS:
      Podoconiosis distribution showed spatial correlation with variation in elevation
      and precipitation. Exploratory analysis identified that phyllosilicate minerals,
      particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline
      silica), iron oxide, and zirconium were associated with podoconiosis prevalence.
      The final multivariate model showed that the quantities of smectite (RR = 2.76,
      95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001)
      and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive
      associations with podoconiosis prevalence. CONCLUSIONS: More quantities of
      smectite, mica and quartz within the soil were associated with podoconiosis
      prevalence. Together with previous work indicating that these minerals may
      influence water absorption, potentiate infection and be toxic to human cells, the
      present findings suggest that these particles may play a role in the pathogenesis
      of podoconiosis and acute adenolymphangitis, a common cause of morbidity in
      podoconiosis patients.

PMID- 24946803
TI  - Probing the inherent stability of siRNA immobilized on nanoparticle constructs.
AB  - Small interfering RNA (siRNA) is a powerful and highly effective method to
      regulate gene expression in vitro and in vivo. However, the susceptibility to
      serum nuclease-catalyzed degradation is a major challenge and it remains unclear
      whether the strategies developed to improve the stability of siRNA free in serum
      solution are ideal for siRNA conjugated to nanoparticle surfaces. Herein, we use
      spherical nucleic acid nanoparticle conjugates, consisting of gold nanoparticles
      (AuNPs) with siRNA chemisorbed to the surface, as a platform to study how a model
      siRNA targeting androgen receptor degrades in serum (SNA-siRNAAR). In solutions
      of 10% (vol/vol) FBS, we find rapid endonuclease hydrolysis at specific sites
      near the AuNP-facing terminus of siRNAAR, which were different from those of
      siRNAAR free in solution. These data indicate that the chemical environment of
      siRNA on a nanoparticle surface can alter the recognition of siRNA by serum
      nucleases and change the inherent stability of the nucleic acid. Finally, we
      demonstrate that incorporation of 2'-O-methyl RNA nucleotides at sites of
      nuclease hydrolysis on SNA-siRNAAR results in a 10-fold increase in siRNA
      lifetime. These data suggest that strategies for enhancing the serum stability of
      siRNA immobilized to nanoparticles must be developed from a dedicated analysis of
      the siRNA-nanoparticle conjugate, rather than a reliance on strategies developed
      for siRNA free in solution. We believe these findings are important for
      fundamentally understanding interactions between biological media and
      oligonucleotides conjugated to nanoparticles for the development of gene
      regulatory and therapeutic agents in a variety of disease models. 

PMID- 24946805
TI  - Stem cell differentiation as a many-body problem.
AB  - Stem cell differentiation has been viewed as coming from transitions between
      attractors on an epigenetic landscape that governs the dynamics of a regulatory
      network involving many genes. Rigorous definition of such a landscape is made
      possible by the realization that gene regulation is stochastic, owing to the
      small copy number of the transcription factors that regulate gene expression and
      because of the single-molecule nature of the gene itself. We develop an
      approximation that allows the quantitative construction of the epigenetic
      landscape for large realistic model networks. Applying this approach to the
      network for embryonic stem cell development explains many experimental
      observations, including the heterogeneous distribution of the transcription
      factor Nanog and its role in safeguarding the stem cell pluripotency, which can
      be understood by finding stable steady-state attractors and the most probable
      transition paths between those attractors. We also demonstrate that the switching
      rate between attractors can be significantly influenced by the gene expression
      noise arising from the fluctuations of DNA occupancy when binding to a specific
      DNA site is slow. 

PMID- 24946804
TI  - Planktonic Euryarchaeota are a significant source of archaeal tetraether lipids
      in the ocean.
AB  - Archaea are ubiquitous in marine plankton, and fossil forms of archaeal
      tetraether membrane lipids in sedimentary rocks document their participation in
      marine biogeochemical cycles for >100 million years. Ribosomal RNA surveys have
      identified four major clades of planktonic archaea but, to date, tetraether
      lipids have been characterized in only one, the Marine Group I Thaumarchaeota.
      The membrane lipid composition of the other planktonic archaeal groups--all
      uncultured Euryarchaeota--is currently unknown. Using integrated nucleic acid and
      lipid analyses, we found that Marine Group II Euryarchaeota (MG-II) contributed
      significantly to the tetraether lipid pool in the North Pacific Subtropical Gyre
      at shallow to intermediate depths. Our data strongly suggested that MG-II also
      synthesize crenarchaeol, a tetraether lipid previously considered to be a unique
      biomarker for Thaumarchaeota. Metagenomic datasets spanning 5 y indicated that
      depth stratification of planktonic archaeal groups was a stable feature in the
      North Pacific Subtropical Gyre. The consistent prevalence of MG-II at depths
      where the bulk of exported organic matter originates, together with their
      ubiquitous distribution over diverse oceanic provinces, suggests that this clade
      is a significant source of tetraether lipids to marine sediments. Our results are
      relevant to archaeal lipid biomarker applications in the modern oceans and the
      interpretation of these compounds in the geologic record.

PMID- 24946807
TI  - Rasch analysis of the modified version of the postural assessment scale for
      stroke patients: postural stroke study in Gothenburg (POSTGOT).
AB  - BACKGROUND: The modified version of the Postural Assessment Scale for Stroke
      Patients (SwePASS) is a new ordinal outcome measurement designed to assess
      postural control in patients with stroke. Before implementation of SwePASS into
      the clinical setting, it is necessary to know its measurement properties. Thus,
      the aim of the study was to evaluate the measurement properties of the SwePASS.
      METHODS: Rasch analysis, based on data of 150 SwePASS assessments was made the
      first week after stroke onset. The measurement properties referred to were
      unidimensionality, local independence, invariance, category function, targeting
      of persons and items and the reliability. RESULTS: The initial analysis showed
      disordered thresholds in four items. After adjustment of the scoring categories,
      this was resolved. However, analyses of local dependency revealed correlations
      between two of the items. These two items were collapsed into one. After
      adjustments, the person separation index that acts as an indicator of the whole
      model fit was 0.96. The adjusted SwePASS is a global scale that works the same
      way regardless of gender, age and location of stroke lesion. Overall, the
      population had better postural control than was targeted with the items in the
      scale. CONCLUSIONS: Rasch analysis of the adjusted SwePASS showed that the scale
      was unidimensional. In SwePASS, equal capacity in postural control provides the
      same response to an individual item in patients with stroke, regardless of
      gender, age and location of stroke lesion. Regarding clinical implications,
      before introducing SwePASS in clinical routine and to confirm the results,
      further research including a larger sample with poorer postural control is
      suggested.

PMID- 24946806
TI  - Murine Joubert syndrome reveals Hedgehog signaling defects as a potential
      therapeutic target for nephronophthisis.
AB  - Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the
      disease remains poorly understood, partly due to the lack of appropriate animal
      models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP
      with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS
      and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most
      common genetic lesion. We present a Cep290 gene trap mouse model of JBTS that
      displays the kidney, eye, and brain abnormalities that define the syndrome.
      Mutant mice present with cystic kidney disease as neonates. Newborn kidneys
      contain normal amounts of lymphoid enhancer-binding factor 1 (Lef1) and
      transcription factor 1 (Tcf1) protein, indicating normal function of the Wnt
      signaling pathway; however, an increase in the protein Gli3 repressor reveals
      abnormal Hedgehog (Hh) signaling evident in newborn kidneys. Collecting duct
      cells from mutant mice have abnormal primary cilia and are unable to form
      spheroid structures in vitro. Treatment of mutant cells with the Hh agonist
      purmorphamine restored normal spheroid formation. Renal epithelial cells from a
      JBTS patient with CEP290 mutations showed similar impairments to spheroid
      formation that could also be partially rescued by exogenous stimulation of Hh
      signaling. These data implicate abnormal Hh signaling as the cause of NPHP and
      suggest that Hh agonists may be exploited therapeutically. 

PMID- 24946808
TI  - Cancer stem cells from epithelial ovarian cancer patients privilege oxidative
      phosphorylation, and resist glucose deprivation.
AB  - We investigated the metabolic profile of cancer stem cells (CSC) isolated from
      patients with epithelial ovarian cancer. CSC overexpressed genes associated with
      glucose uptake, oxidative phosphorylation (OXPHOS), and fatty acid beta
      oxidation, indicating higher ability to direct pyruvate towards the Krebs cycle.
      Consistent with a metabolic profile dominated by OXPHOS, the CSC showed higher
      mitochondrial reactive oxygen species (ROS) production and elevated membrane
      potential, and underwent apoptosis upon inhibition of the mitochondrial
      respiratory chain. The CSC also had a high rate of pentose phosphate pathway
      (PPP) activity, which is not typical of cells privileging OXPHOS over glycolysis,
      and may rather reflect the PPP role in recharging scavenging enzymes.
      Furthermore, CSC resisted in vitro and in vivo glucose deprivation, while
      maintaining their CSC phenotype and OXPHOS profile. These observations may
      explain the CSC resistance to anti-angiogenic therapies, and indicate this
      peculiar metabolic profile as a possible target of novel treatment strategies. 

PMID- 24946809
TI  - Vulvar lipoma: a case report.
AB  - INTRODUCTION: Vulvar lipoma is a rare tumor localization and only a few cases
      have been reported. The clinical characteristics of vulvar lipoma are well known.
      However, it is important to distinguish lipomas from liposarcomas. We report a
      case of vulvar lipoma and discuss its clinical features, including diagnostic
      aspects, with emphasis on histopathological evaluation of all excised lesions. We
      also report and discuss patient management and treatment outcomes. CASE
      PRESENTATION: We report the case of a 27-year-old Moroccan woman. Our patient
      presented with a painless and slow-growing right vulvar mass that had evolved
      over one year, which had suddenly become uncomfortable when walking. A physical
      examination revealed a single soft and pasty mass in her left labium majus, which
      could be mobilized under her skin towards her mons pubis. The largest dimension
      of the mass measured 6cm. Magnetic resonance imaging showed a homogenous
      hyperintense mass with a well-defined contour in her left labium majus; a fat
      suppressed magnetic resonance image demonstrated a marked signal intensity
      decrease. The mass was completely removed surgically. A histological examination
      revealed a circumscribed benign tumor composed of mature adipocytes, confirming
      the diagnosis of vulvar lipoma. CONCLUSION: Vulvar lipomas must be differentiated
      from liposarcomas, which demonstrate very similar clinical and imaging profiles.
      The final diagnosis should be based on histopathological evaluation. A precise
      diagnosis should allow for appropriate surgical treatment.

PMID- 24946811
TI  - Fluralaner, a novel isoxazoline, prevents flea (Ctenocephalides felis)
      reproduction in vitro and in a simulated home environment.
AB  - BACKGROUND: Fluralaner, a novel isoxazoline, has both acaricidal and insecticidal
      activity through potent blockage of GABA- and L-glutamate-gated chloride
      channels. This study investigated the in vitro and in vivo effects of fluralaner
      exposure on flea (Ctenocephalides felis) reproduction. METHODS: Blood spiked with
      sub-insecticidal fluralaner concentrations (between 0.09 and 50.0 ng/mL) was fed
      to fleas for 10 days using a membrane system. Cessation of reproduction in
      exposed fleas was assessed using flea survival, egg hatchability, and control of
      oviposition, pupae, and flea emergence. Fluralaner efficacy for in vivo
      Ctenocephalides (C.) felis control on dogs was assessed using a simulated flea
      infested home environment. During a pre-treatment period, dogs were infested
      twice on days -28 and -21 with 100 adult unfed fleas to establish a thriving
      population by day 0 of the study. On day 0, one group of dogs was treated with
      fluralaner (BravectoTM; n=10), while another group served as negative control
      (n=10). Following treatment, dogs were infested three times with 50 fleas on days
      22, 50 and 78 to simulate new infestations. Live flea counts were conducted
      weekly on all dogs for 12 weeks starting 1 day before treatment. RESULTS:
      Fluralaner potently inhibited flea reproduction capacity in vitro. Oviposition
      ceased completely at concentrations as low as 25.0 ng/mL. While no ovicidal
      effect was observed, fluralaner exerted a larvicidal effect at exceptionally low
      concentrations (6.25 ng/mL). In the simulated flea-infested home environment,
      flea-control efficacy on fluralaner-treated dogs was >99% at every time point
      measured for 12 weeks. No adverse events were observed in fluralaner-treated
      dogs. CONCLUSIONS: Fluralaner completely controls egg laying, larval development
      and flea reproduction even at sub-insecticidal concentrations. Oral treatment of
      dogs with fluralaner is highly effective for eliminating fleas in a simulated
      flea-infested home environment.

PMID- 24946812
TI  - Judging performance in general medicine.

PMID- 24946810
TI  - Repression of chimeric transcripts emanating from endogenous retrotransposons by
      a sequence-specific transcription factor.
AB  - BACKGROUND: Retroviral elements are pervasively transcribed and dynamically
      regulated during development. While multiple histone- and DNA-modifying enzymes
      have broadly been associated with their global silencing, little is known about
      how the many diverse retroviral families are each selectively recognized.
      RESULTS: Here we show that the zinc finger protein Kruppel-like Factor 3 (KLF3)
      specifically silences transcription from the ORR1A0 long terminal repeat in
      murine fetal and adult erythroid cells. In the absence of KLF3, we detect
      widespread transcription from ORR1A0 elements driven by the master erythroid
      regulator KLF1. In several instances these aberrant transcripts are spliced to
      downstream genic exons. One such chimeric transcript produces a novel, dominant
      negative isoform of PU.1 that can induce erythroid differentiation. CONCLUSIONS:
      We propose that KLF3 ensures the integrity of the murine erythroid transcriptome
      through the selective repression of a particular retroelement and is likely one
      of multiple sequence-specific factors that cooperate to achieve global silencing.

PMID- 24946813
TI  - New oral anticoagulants: a practical guide on prescription, laboratory testing
      and peri-procedural/bleeding management. Australasian Society of Thrombosis and
      Haemostasis.
AB  - New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin
      to prevent systemic embolism in patients with non-valvular atrial fibrillation
      and for the treatment and prevention of venous thromboembolism. An in-depth
      understanding of their pharmacology is invaluable for appropriate prescription
      and optimal management of patients receiving these drugs should unexpected
      complications (such as bleeding) occur, or the patient requires urgent surgery.
      The Australasian Society of Thrombosis and Haemostasis has set out to inform
      physicians on the use of the different NOAC based on current available evidence
      focusing on: (i) selection of the most suitable patient groups to receive NOAC,
      (ii) laboratory measurements of NOAC in appropriate circumstances and (iii)
      management of patients taking NOAC in the perioperative period, and strategies to
      manage bleeding complications or 'reverse' the anticoagulant effects for urgent
      invasive procedures. 

PMID- 24946814
TI  - Renal drug dosing recommendations: evaluation of product information for brands
      of the same drug.
AB  - OBJECTIVES: To review the product information (PI) for various brands of the same
      generic drugs and investigate the extent to which information is currently
      available on dosing in renal impairment and the concordance between the dosing
      recommendations for the same generic drug. METHOD: The Monthly Index of Medical
      Specialities (MIMS) was examined for 28 generic drugs recommended to be used with
      caution in renal impairment. For each generic drug all available brands listed as
      having solid oral dosage form were recorded. For each identified brand, the
      current PI was consulted and data referring to renal impairment was collated. The
      dissimilarity between these PI regarding the renal dosage recommendation was
      determined. RESULTS: There was generally a lack of detailed information in the PI
      on the use of drugs in patients with renal impairment. The majority of PI
      documents (88 of 155 PI; 57%) provided quantitative dosage recommendations, but
      this was often not detailed enough to help users to make an informed decision.
      For 37 PI documents (24%), an altered dosage regimen was proposed without a
      quantifiable measure of renal function reported in the dose recommendation. The
      renal function severity category terms used and the associated quantitative
      values were also not consistent. It was observed that the recommendations varied
      among different brands of hydromorphone, morphine, oxycodone, tramadol, metformin
      and topiramate. CONCLUSION: The reporting of renal function quantification
      methods, and associated dosage recommendations, in PI requires standardisation to
      ensure optimal drug dosing. Regularly updating of PI is also necessary.

PMID- 24946815
TI  - Progression of KRAS mutant pancreatic adenocarcinoma during vemurafenib treatment
      in a patient with metastatic melanoma.
AB  - Vemurafenib is a tyrosine kinase inhibitor of BRAF that prolongs survival in
      patients with BRAF V600-mutant metastatic melanoma. Secondary cutaneous
      malignancies are a well-documented toxicity of vemurafenib, thought to be
      mediated by enhanced ERK signalling in BRAF wild-type, RAS-mutant cells.
      Vemurafenib could also promote growth of non-cutaneous secondary malignancies by
      a similar mechanism. We present a case of an individual who received vemurafenib
      for metastatic melanoma and experienced rapid growth of a pre-existing KRAS
      mutant pancreatic adenocarcinoma. 

PMID- 24946817
TI  - Gastrointestinal amyloidosis in Australian indigenous patients.
AB  - This study documents the symptoms, racial distribution, pathological findings and
      outcomes of patients diagnosed with gastrointestinal amyloidosis in Alice Springs
      Hospital. In a 4 year retrospective survey. 9 patients, all indigenous, 7F/2M,
      had biopsy proven gastrointestinal amyloidosis. Four out of four patients tested
      were found to have AA amyloidosis. Presenting symptoms included diarrhoea, bloody
      in some, vomiting and abdominal pain. All but one had diabetes mellitus, type 2.
      Multiple infections were common and most patients had low serum albumin and
      transferrin concentrations but high serum ferritin concentrations. Five of the
      patients died, and the gastrointestinal symptoms of the remaining 4 remitted.
      Gastrointestinal amyloidosis should be included in the differential diagnosis of
      indigenous patients presenting with chronic diarrhoea, vomiting or abdominal
      pain. It carries a grave prognosis, is probably secondary to chronic infections
      but is potentially reversible. 

PMID- 24946818
TI  - Diagnostic utility of bone marrow examination for the assessment of patients with
      fever of unknown origin: a 10-year single-centre experience.
AB  - Bone marrow (BM) examination is included in the diagnostic algorithm of fever of
      unknown origin (FUO), although its role is not clearly determined. The purpose of
      this study was to assess the role of BM studies in patients with FUO. We
      retrospectively reviewed 45 consecutive patients (25% human immunodeficiency
      virus-positive) with FUO who underwent a BM study in the University Hospital of
      Salamanca from 2000 to 2010. We analysed the diagnostic role of BM smears,
      multiparameter flow cytometry analysis, histology and microbiological cultures.
      Five patients (11%) were finally diagnosed by BM study (three had an infectious
      disease and two were found to have haematological malignancies), all of whom were
      immunocompetent patients. Histology was the most useful study (diagnosis was
      obtained in 4/5 patients), while BM cultures did not establish the final
      diagnosis in any patient. Flow cytometry established the diagnosis in one
      patient, although this patient was also diagnosed by histology. In conclusion, BM
      study is useful for establishing the aetiology of FUO. BM biopsy for histological
      examination should be always mandatory if a BM examination is performed. 

PMID- 24946816
TI  - Liver transplantation for the treatment of homozygous familial
      hypercholesterolaemia in an era of emerging lipid-lowering therapies.
AB  - Homozygous familial hypercholesterolaemia (FH) causes severe premature coronary
      artery disease because of very high levels of low density lipoprotein (LDL)
      cholesterol. Standard lipid-lowering drugs and LDL-apheresis may not be
      sufficiently effective. Liver transplantation replaces defective LDL receptors
      and vastly improves the lipid profile, and we present the first report of an
      Australian adult to receive this treatment. Emerging drug treatments for FH may
      be alternatives to LDL-apheresis and transplantation, but long-term safety and
      efficacy data are lacking for all of these options. 

PMID- 24946819
TI  - CORB is the best pneumonia severity score for elderly hospitalised patients with
      suspected pneumonia.
AB  - Pneumonia severity scoring systems have been developed to identify patients at
      highest mortality risk, and are used in guidelines to limit use of broad-spectrum
      antibiotics to patients with severe community-acquired pneumonia. A retrospective
      audit of hospitalised general internal medicine patients with pneumonia was
      performed to assess the diagnostic performance of various pneumonia severity
      scores in an elderly general internal medicine population. 

PMID- 24946820
TI  - High-dose methylprednisolone is effective in treating radiation-induced
      refractory haemorrhagic cystitis.

PMID- 24946821
TI  - Xanthelasma palpebrarum responding to interleukin-1 blockade.

PMID- 24946822
TI  - Management of comorbidities in patients with complex diseases: who is
      responsible?

PMID- 24946823
TI  - Polypharmacy in palliative care: optimising medications is an ongoing challenge.

PMID- 24946825
TI  - Abstracts of the 56th Annual Meeting of the American Headache Society, June 26
      29, 2014, Los Angeles, CA.

PMID- 24946824
TI  - Measurement properties of the Western Ontario Shoulder Instability index in Dutch
      patients with shoulder instability.
AB  - BACKGROUND: The Western Ontario Shoulder Instability index (WOSI) is a patient
      reported outcome measure for patients with shoulder instability. The purpose of
      this study was to validate the WOSI in a Dutch population by evaluating its
      structural validity, internal consistency, measurement error, reliability, and
      construct validity. Floor and ceiling effects were also addressed. METHODS: Two
      cohorts were recruited, including a total of 138 patients with shoulder
      instability. Confirmatory factor analysis was used to assess the structural
      validity and Cronbach's alpha to assess internal consistency. The measurement
      error was calculated as the smallest detectable change (SDC). Reliability (test
      retest) was estimated in a subgroup of 99 patients who completed the re-test
      after a mean of 13 days (5-30 days). Reliability was calculated with the
      intraclass correlation coefficient (ICC). Construct validity was evaluated by
      comparing the WOSI with the Oxford Shoulder Instability Score (OSIS), the Simple
      Shoulder Test, the Oxford Shoulder Score, the Disability of the Arm, Shoulder,
      and Hand assessment (DASH), and the Short Form-36 Health Survey. Measurement
      properties were evaluated for both the total WOSI score and its four domains.
      RESULTS: Factor analysis did not confirm the validity of the four domains. Best
      results were found for a one-factor model. Internal consistency was good, with
      Cronbach's alpha ranging from 0.93 to 0.96. Reliability was excellent (ICC 0.88
      0.92 for all subscales). The measurement error (SDC) was 23.0% for the total WOSI
      and 23% to 28% for the subscales (on a scale of 0-100). Regarding the construct
      validity, 76% of the results were in accordance with the hypotheses, including a
      high correlation with the OSIS (0.82) and DASH (0.81) assessments. No floor or
      ceiling effects were found. CONCLUSION: The Dutch version of WOSI showed good
      reliability and validity in a cohort of patients with shoulder instability,
      although the factor structure remains unclear.

PMID- 24946826
TI  - Periodontitis in coronary heart disease patients: strong association between
      bleeding on probing and systemic biomarkers.
AB  - AIM: Few studies have examined the relationship of individual periodontal
      parameters with individual systemic biomarkers. This study assessed the possible
      association between specific clinical parameters of periodontitis and systemic
      biomarkers of coronary heart disease risk in coronary heart disease patients with
      periodontitis. MATERIALS AND METHODS: Angiographically proven coronary heart
      disease patients with periodontitis (n = 317), aged >30 years and without other
      systemic illness were examined. Periodontal clinical parameters of bleeding on
      probing (BOP), probing depth (PD), and clinical attachment level (CAL) and
      systemic levels of high-sensitivity C-reactive protein (CRP), fibrinogen (FIB)
      and white blood cells (WBC) were noted and analyzed to identify associations
      through linear and stepwise multiple regression analyses. RESULTS: Unadjusted
      linear regression showed significant associations between periodontal and
      systemic parameters; the strongest association (r = 0.629; p < 0.001) was found
      between BOP and CRP levels, the periodontal and systemic inflammation marker,
      respectively. Stepwise regression analysis models revealed that BOP was a
      predictor of systemic CRP levels (p < 0.0001). BOP was the only periodontal
      parameter significantly associated with each systemic parameter (CRP, FIB, and
      WBC). CONCLUSION: In coronary heart disease patients with periodontitis, BOP is
      strongly associated with systemic CRP levels; this association possibly reflects
      the potential significance of the local periodontal inflammatory burden for
      systemic inflammation.

PMID- 24946827
TI  - Structural insights into yeast histone chaperone Hif1: a scaffold protein
      recruiting protein complexes to core histones.
AB  - Yeast Hif1 [Hat1 (histone acetyltransferase 1)-interacting factor], a homologue
      of human NASP (nuclear autoantigenic sperm protein), is a histone chaperone that
      is involved in various protein complexes which modify histones during telomeric
      silencing and chromatin reassembly. For elucidating the structural basis of Hif1,
      in the present paper we demonstrate the crystal structure of Hif1 consisting of a
      superhelixed TPR (tetratricopeptide repeat) domain and an extended acid loop
      covering the rear of TPR domain, which represent typical characteristics of SHNi
      TPR [Sim3 (start independent of mitosis 3)-Hif1-NASP interrupted TPR] proteins.
      Our binding assay indicates that Hif1 could bind to the histone octamer via
      histones H3 and H4. The acid loop is shown to be crucial for the binding of
      histones and may also change the conformation of the TPR groove. By binding to
      the core histone complex Hif1 may recruit functional protein complexes to modify
      histones during chromatin reassembly. 

PMID- 24946828
TI  - Leaf phenomics: a systematic reverse genetic screen for Arabidopsis leaf mutants.
AB  - The study and eventual manipulation of leaf development in plants requires a
      thorough understanding of the genetic basis of leaf organogenesis. Forward
      genetic screens have identified hundreds of Arabidopsis mutants with altered leaf
      development, but the genome has not yet been saturated. To identify genes
      required for leaf development we are screening the Arabidopsis Salk Unimutant
      collection. We have identified 608 lines that exhibit a leaf phenotype with full
      penetrance and almost constant expressivity and 98 additional lines with
      segregating mutant phenotypes. To allow indexing and integration with other
      mutants, the mutant phenotypes were described using a custom leaf phenotype
      ontology. We found that the indexed mutation is present in the annotated locus
      for 78% of the 553 mutants genotyped, and that in half of these the annotated T
      DNA is responsible for the phenotype. To quickly map non-annotated T-DNA
      insertions, we developed a reliable, cost-effective and easy method based on
      whole-genome sequencing. To enable comprehensive access to our data, we
      implemented a public web application named PhenoLeaf
      (http://genetics.umh.es/phenoleaf) that allows researchers to query the results
      of our screen, including text and visual phenotype information. We demonstrated
      how this new resource can facilitate gene function discovery by identifying and
      characterizing At1g77600, which we found to be required for proximal-distal cell
      cycle-driven leaf growth, and At3g62870, which encodes a ribosomal protein needed
      for cell proliferation and chloroplast function. This collection provides a
      valuable tool for the study of leaf development, characterization of biomass
      feedstocks and examination of other traits in this fundamental photosynthetic
      organ. 

PMID- 24946829
TI  - Management of BU-HIV co-infection.
AB  - BACKGROUND: Buruli Ulcer (BU)-HIV co-infection is an important emerging
      management challenge for BU disease. Limited by paucity of scientific studies,
      guidance for management of this co-infection has been lacking. METHODS: Initiated
      by WHO, a panel of experts in BU and HIV management developed guidance principles
      for the management of BU-HIV co-infection based on review of available scientific
      evidence, current treatment experience, and global recommendations established
      for management of HIV infection and tuberculosis. RESULTS: The expert panel
      agreed that all BU patients should be offered quality provider-initiated HIV
      testing and counselling. In areas with high prevalence of malaria and/or
      bacterial infections, all patients with HIV co-infection should be started on
      cotrimoxazole preventative therapy. Combination antibiotic treatment for BU
      should be commenced before starting antiretroviral therapy (ART) and provided for
      8 weeks duration. The suggested combination is rifampicin (10 mg/kg daily up to a
      maximum of 600 mg/day) plus streptomycin (15 mg/kg daily). An alternative regimen
      is rifampicin plus clarithromycin (7.5 mg/kg twice daily up to a maximum of 1000
      mg daily) although due to drug interactions with antiretroviral drugs this
      regimen should be used with caution. ART should be initiated in all BU-HIV co
      infected patients with symptomatic HIV disease (WHO clinical stage 3 or 4)
      regardless of CD4 cell count and in asymptomatic individuals with CD4 count <=500
      cells/mm(3) . If CD4 count is not available, BU-HIV co-infected individuals with
      category 2 or 3 BU disease should be offered ART. For eligible individuals, ART
      should be commenced as soon as possible within 8 weeks after commencing BU
      treatment, and as a priority in those with advanced HIV disease (CD4 <= 350
      cells/mm(3) or WHO stage 3 or 4 disease). All co-infected patients should be
      actively screened for tuberculosis before commencing BU treatment and before
      starting ART. Programmes should implement a monitoring and reporting system to
      document the outcomes of BU-HIV interventions. CONCLUSIONS: Knowledge of the
      clinical and epidemiological interactions between BU and HIV disease is limited.
      While awaiting more urgently needed evidence, current management practice of both
      diseases has been useful to build simple 'common sense' preliminary guidance on
      how to manage BU-HIV co-infection.

PMID- 24946830
TI  - A unifying model of genome evolution under parsimony.
AB  - BACKGROUND: Parsimony and maximum likelihood methods of phylogenetic tree
      estimation and parsimony methods for genome rearrangements are central to the
      study of genome evolution yet to date they have largely been pursued in
      isolation. RESULTS: We present a data structure called a history graph that
      offers a practical basis for the analysis of genome evolution. It conceptually
      simplifies the study of parsimonious evolutionary histories by representing both
      substitutions and double cut and join (DCJ) rearrangements in the presence of
      duplications. The problem of constructing parsimonious history graphs thus
      subsumes related maximum parsimony problems in the fields of phylogenetic
      reconstruction and genome rearrangement. We show that tractable functions can be
      used to define upper and lower bounds on the minimum number of substitutions and
      DCJ rearrangements needed to explain any history graph. These bounds become tight
      for a special type of unambiguous history graph called an ancestral variation
      graph (AVG), which constrains in its combinatorial structure the number of
      operations required. We finally demonstrate that for a given history graph G, a
      finite set of AVGs describe all parsimonious interpretations of G, and this set
      can be explored with a few sampling moves. CONCLUSION: This theoretical study
      describes a model in which the inference of genome rearrangements and phylogeny
      can be unified under parsimony.

PMID- 24946832
TI  - Facile graphene n-doping by wet chemical treatment for electronic applications.
AB  - We report a post-synthetic n-doping method for chemical-vapor-deposition (CVD)
      grown graphene using wet chemical processing. An ammonium fluoride solution was
      found effective in converting pristine hole doping into electron doping in
      addition to the mobility improvement of charge carriers. We verified the doping
      by electrical measurements, Raman spectroscopy and X-ray photoelectron
      spectroscopy (XPS) analyses and suggest that the mechanism of n-doping is
      electrostatic doping by ionic physisorption of ammonium ions on the graphene
      surface. This simple chemical doping method provides a facile and robust route to
      n-doping of large area graphene for the realization of high performance graphene
      based electronic devices. 

PMID- 24946831
TI  - Identification and characterization of Mini1, a gene regulating rice shoot
      development.
AB  - The aerial parts of higher plants are generated from the shoot apical meristem
      (SAM). In this study, we isolated a small rice (Oryza sativa L.) mutant that
      showed premature termination of shoot development and was named mini rice 1
      (mini1). The mutant was first isolated from a japonica cultivar Zhonghua11 (ZH11)
      subjected to ethyl methanesulfonate (EMS) treatment. With bulked segregant
      analysis (BSA) and map-based cloning method, Mini1 gene was finally fine-mapped
      to an interval of 48.6 kb on chromosome 9. Sequence analyses revealed a single
      base substitution from G to A was found in the region, which resulted in an amino
      acid change from Gly to Asp. The candidate gene Os09g0363900 was predicted to
      encode a putative adhesion of calyx edges protein ACE (putative HOTHEAD
      precursor) and genetic complementation experiment confirmed the identity of
      Mini1. Os09g0363900 contains glucose-methanol-choline (GMC) oxidoreductase and
      NAD(P)-binding Rossmann-like domain, and exhibits high similarity to Arabidopsis
      HOTHEAD (HTH). Expression analysis indicated Mini1 was highly expressed in young
      shoots but lowly in roots and the expression level of most genes involved in
      auxin biosynthesis and signal transduction were reduced in mutant. We conclude
      that Mini1 plays an important role in maintaining SAM activity and promoting
      shoot development in rice. 

PMID- 24946834
TI  - Direct access to midlevel dental providers: an evidence synthesis.
AB  - OBJECTIVES: Direct access is a term that describes the ability of patients to
      seek health care from midlevel dental providers (MLDPs) without first seeing a
      dentist. The objective of this study was to synthesize the evidence for the
      effects and costs of direct access to MLDPs in a primary dental care environment
      and assess the attitudes of various stakeholders to this method of care delivery.
      METHODS: The literature was examined for descriptive, observational, and
      experimental study designs to examine the evidence for direct access in
      dentistry. Electronic searches were undertaken of the Database of Abstracts of
      Reviews of Effectiveness, bibliographic subscription databases, open access
      databases, and the gray literature. RESULTS: The search identified 371 records,
      although the extent of experimental evidence was limited. The majority of
      included studies were descriptive and recorded the subjective views of different
      stakeholders, following the introduction of the policy. CONCLUSIONS: The limited
      extent of experimental evidence regarding direct access to MLDPs contrasts with
      their widespread use across Europe, the United States, and the southern
      hemisphere. Suggestions are made for a research program to improve the evidence
      base for direct access.

PMID- 24946833
TI  - Predicting use of ineffective vegetable parenting practices with the Model of
      Goal Directed Behavior.
AB  - OBJECTIVE: Increasing a parent's ability to influence a child's vegetable intake
      may require reducing the parent's use of ineffective vegetable parenting
      practices. The present study was designed to understand the psychosocial
      influences on ineffective vegetable parenting practices. DESIGN: A cross
      sectional web-based survey was conducted to model use of ineffective vegetable
      parenting practices using validated scales from a Model of Goal Directed
      Vegetable Parenting Practices. SETTING: The dependent variable was a composite
      ineffective vegetable parenting practices index. The independent variables
      included validated subscales of intention, habit, perceived barriers, desire,
      competence, autonomy, relatedness, attitudes, norms, perceived behavioural
      control and anticipated emotions. Models were analysed using block regression
      with backward deletion. SUBJECTS: Parents of 307 pre-school children (3-5 years
      old). RESULTS: Variables significantly positively related to ineffective
      vegetable parenting practices in order of relationship strength included habit of
      controlling vegetable practices (standardized beta=0.349, P<0.0001) and desire
      (standardized beta=0.117, P=0.025). Variables significantly negatively related to
      ineffective vegetable parenting practices in order of relationship strength
      included perceived behavioural control of negative parenting practices
      (standardized beta=-0.215, P<0000), the habit of active child involvement in
      vegetable selection (standardized beta=-0.142, P=0.008), anticipated negative
      parent emotional response to child vegetable refusal (standardized beta=-0.133,
      P=0.009), autonomy (standardized beta=-0.118, P=0.014), attitude about negative
      effects of vegetables (standardized beta=-0.118, P=0.015) and descriptive norms
      (standardized beta=-0.103, P=0.032). The model accounted for 40.5 % of the
      variance in use of ineffective vegetable parenting practices. CONCLUSIONS: The
      present study is the first report of psychometrically tested scales to predict
      use of ineffective vegetable parenting practices. Innovative intervention
      procedures will need to be designed and tested to reduce ineffective vegetable
      parenting practices.

PMID- 24946835
TI  - Atrial pacing site and atrioventricular conduction in patients paced for sinus
      node disease.
AB  - BACKGROUND: Unnecessary ventricular pacing in sinus node disease (SND) must be
      avoided. To test the hypothesis that in SND, with or without 1st degree
      atrioventricular (AV) block, cumulative percent ventricular pacing (cum%VP) can
      be limited by low right atrial septal (LRAS) instead of right atrial appendage
      (RAA) pacing. METHODS: We studied 102 dual-chamber pacemaker recipients with SND.
      The PQ interval on 12-lead electrocardiogram and the atrial paced to ventricular
      sensed interval (Ap-Vs) during LRAS and RAA pacing were measured and compared at
      implantation, 3 months and 1 year of follow-up. Group 1 included 62 patients with
      baseline PQ interval <200 milliseconds during LRAS (n = 28) versus RAA (n = 34)
      pacing. Group 2 included 40 patients with baseline PQ >=200 milliseconds during
      LRAS (n = 20) versus RAA (n = 20) pacing. cum%VP were measured at 3 months and 1
      year. RESULTS: The characteristics and AV conduction properties were similar and
      the Ap-Vs interval was significantly shorter in the LRAS than in the RAA pacing
      group up to 1 year (193 +/- 32 milliseconds vs. 220 +/- 27 milliseconds in Group
      1; P = 0.003, 222 +/- 41 milliseconds vs. 281 +/- 30 milliseconds in Group 2; P <
      0.001). While cumulative percent atrial pacing was consistently similar, cum%VP
      was significantly smaller during LRAS than RAA pacing (1 +/- 1% vs. 8 +/- 18% in
      Group 1; P = 0.03, 7 +/- 10% vs. 48 +/- 38% in Group 2; P < 0.001). Similar
      observations were made with or without left atrial (LA) enlargement. CONCLUSION:
      Compared with RAA, LRAS pacing showed shorter AV interval in SND patients with or
      without 1st degree AV block and LA enlargement. This beneficial effect persisted
      through 1-year follow-up, and decreased cum%VP significantly.

PMID- 24946836
TI  - Catalytic carbene transfer allows the direct customization of cyclic purine
      dinucleotides.
AB  - We describe a simple method for the direct modification of nucleobases in cyclic
      purine dinucleotides, important signalling molecules in both prokaryotes and
      eukaryotes. The method tolerates all members of the cyclic dinucleotide family
      and could be used to modulate their function or introduce useful side-chains such
      as fluorophores and photo-crosslinking groups. 

PMID- 24946837
TI  - Correlated defect nanoregions in a metal-organic framework.
AB  - Throughout much of condensed matter science, correlated disorder is a key to
      material function. While structural and compositional defects are known to exist
      within a variety of metal-organic frameworks (MOFs), the prevailing understanding
      is that these defects are only ever included in a random manner. Here we show-
      using a combination of diffuse scattering, electron microscopy, anomalous X-ray
      scattering and pair distribution function measurements--that correlations between
      defects can in fact be introduced and controlled within a hafnium terephthalate
      MOF. The nanoscale defect structures that emerge are an analogue of correlated
      Schottky vacancies in rocksalt-structured transition metal monoxides and have
      implications for storage, transport, optical and mechanical responses. Our
      results suggest how the diffraction behaviour of some MOFs might be
      reinterpreted, and establish a strategy of exploiting correlated nanoscale
      disorder as a targetable and desirable motif in MOF design.

PMID- 24946839
TI  - Promising ZnO-based DSSC performance using HMP molecular dyes of high extinction
      coefficients.
AB  - Employing newly synthesized di-substituted tri-phenyl amine (HMP-9) and carbazole
      (HMP-11) dyes (with limited acidic carboxyl anchor groups), a power conversion
      efficiency as high as 7.03% in ZnO nanocrystallite (NC)-based dye-sensitized
      solar cells (DSSCs) is achieved. The specific molecular designs of HMP-09 and HMP
      11 consisting of with and without hexyloxy spacer groups, and added tri-phenyl
      amine or 9-phenyl-9H-carbazole donor groups, respectively, attached on the
      ancillary ligands are advantageous, evidenced from electrochemical impedance
      spectroscopy measurements, for ZnO NC-based DSSCs. 

PMID- 24946838
TI  - The importance of B cell CD1d expression for humoral immunity.
AB  - It was reported over a decade previously that CD1d-restricted Natural Killer T
      (NKT) cells could interact with CD1d-expressing B cells and facilitate antibody
      secretion. Since then, several studies have observed that NKT cells can provide B
      cell help for production of antibody against model and pathogen-derived
      glycolipids, carbohydrates and proteins. In regard to T cell-dependent protein
      antigens, it is still not entirely clear to what extent cognate interactions
      between CD1d-expressing B cells and NKT cells contribute to initial and long
      lived B-cell responses that are characteristic of such antigens. In this
      editorial, we review evidence that NKT cells provide CD1d-dependent cognate and
      non-cognate forms of B-cell help following immunization with protein antigen.
      Elucidating these mechanisms will be important for harnessing NKT cells during
      vaccination. 

PMID- 24946840
TI  - Working memory capacity predicts the beneficial effect of selective memory
      retrieval.
AB  - Selective retrieval of some studied items can both impair and improve recall of
      the other items. This study examined the role of working memory capacity (WMC)
      for the two effects of memory retrieval. Participants studied an item list
      consisting of predefined target and nontarget items. After study of the list,
      half of the participants performed an imagination task supposed to induce a
      change in mental context, whereas the other half performed a counting task which
      does not induce such context change. Following presentation of a second list,
      memory for the original list's target items was tested, either with or without
      preceding retrieval of the list's nontarget items. Consistent with previous work,
      preceding nontarget retrieval impaired target recall in the absence of the
      context change, but improved target recall in its presence. In particular, there
      was a positive relationship between WMC and the beneficial, but not the
      detrimental effect of memory retrieval. On the basis of the view that the
      beneficial effect of memory retrieval reflects context-reactivation processes,
      the results indicate that individuals with higher WMC are better able to
      capitalise on retrieval-induced context reactivation than individuals with lower
      WMC. 

PMID- 24946841
TI  - An Escherichia coli trap in human serum albumin microtubes.
AB  - We describe the template synthesis of human serum albumin microtubes (MTs) and
      highlight their Escherichia coli (E. coli) trapping capability with extremely
      high efficiency. The E. coli was loaded into the one-dimensional pore space
      interior of the tubule. Similar MTs including an Fe3O4 layer also captured E.
      coli and were manipulated by exposure to a magnetic field. 

PMID- 24946842
TI  - Visual tracking combined with hand-tracking improves time perception of moving
      stimuli.
AB  - A number of studies have shown that performing a secondary task while executing a
      time-judgment task impairs performance on the latter task. However, this turns
      out not to be the case for certain motor secondary tasks. We show that
      concomitant secondary motor tasks involving pointing, when performed during a
      time-judgment task, can actually improve our time-judgment abilities. We compared
      adult participants' performance in a time-of-movement paradigm with visual
      pursuit-only and with visual pursuit plus hand pursuit. Rather than interfering
      with their estimation of stimulus movement duration, the addition of hand pursuit
      significantly improved their judgment. In addition, we considered the effect of
      three different movement profiles and four different movement speeds for the
      moving stimulus. As predicted by Vierordt's law, time judgments of shorter
      stimuli are overestimated and longer stimuli underestimated. Finally, timing
      performances appear to improve when the moving target follows a "biological"
      velocity profile. 

PMID- 24946843
TI  - Photodynamic therapy for central serous chorioretinopathy.
AB  - PURPOSE: Central serous chorioretinopathy (CSCR) is an idiopathic disorder
      characterised by detachment of the neurosensory retina due to serous fluid
      accumulation between the photoreceptor outer segments and the retinal pigment
      epithelium. There are currently no set guidelines or protocols on its treatment.
      This study was undertaken to assess the current literature on the the efficacy
      and safety of photodynamic therapy (PDT) as a treatment option for CSCR. METHODS:
      Seven databases (PubMed, CENTRAL, MEDLINE, Web of Science, Embase, Scopus, and
      The Cochrane Database of Systematic Reviews) were searched without restrictions
      on time or location. We followed PRISMA guidelines and evaluated quality
      according to STROBE criteria. In total, 117 citations were identified and 31
      studies describing 787 eyes were included for review. Data on indications for PDT
      in CSCR, dosing regimens of verteprofin PDT (which includes treatment dose of
      vertoporfin, treatment time, fluence, and spot size), number of treatment
      sessions, response to treatment, mean length of follow-up, and complications were
      extracted and analysed. RESULTS: Since the introduction of PDT for the treatment
      of CSCR in 2003, there have been three randomised controlled trials (RCTs), one
      for acute and two chronic CSCR and 28 further studies that met the STROBE
      criteria that compared the use of PDT with other treatment options. All studies
      showed short-term efficacy of PDT in CSCR. The studies were of small sample size
      and lacked sufficient follow-up to draw conclusions on long-term efficacy and
      safety. CONCLUSIONS: There is sufficient scientific evidence to suggest that PDT
      may be a useful treatment option for chronic CSCR in the short-term. The review
      identifies a need for robust RCTs with longer follow-up to ascertain the role of
      PDT as a useful treatment option for CSCR.

PMID- 24946844
TI  - Intraoperative usefulness and postoperative results of the endoilluminator for
      performing primary posterior capsulectomy and anterior vitrectomy during
      pediatric cataract surgery.
AB  - PURPOSE: To analyze the intraoperative usefulness and postoperative results of
      endoilluminator use during pediatric cataract surgery. METHODS: Medical records
      of children <8 years of age who underwent lens aspiration with primary posterior
      capsulectomy (PPC) and anterior vitrectomy (AV) with or without intraocular lens
      implantation (IOL) were studied. An endoilluminator was used intraoperatively as
      an external light source in all cases to ensure the completeness of PPC and
      adequacy of AV. All children were divided into three groups depending upon the
      age at surgery and presence of IOL. We included only the first operated eye in
      bilateral cases. We studied the intraoperative performance for all and
      postoperative complications for those with >6 months follow-up. RESULTS: The
      charts of 79 eyes of 46 children (26 boys, 20 girls: 33 bilateral, 13 unilateral)
      were reviewed, of which we analyzed 46 eyes of 46 children for intraoperative
      performance and 42 eyes of 42 children for postoperative complications. The
      intraoperatively adequate size of PPC was obtained in all cases with no vitreous
      in the anterior chamber. Two cases in the first group developed peaking of the
      pupil, and one case developed visual axis contraction requiring membranectomy.
      None of the cases in the other groups developed any complication. CONCLUSION: An
      endoilluminator is a simple, safe, and powerful tool for better visualization of
      the posterior capsule and anterior vitreous during pediatric cataract surgery. It
      helps in confirming a good vitrectomy, ensuring its completeness and thereby
      reducing the chances of any complication due to inadequate AV.

PMID- 24946845
TI  - Long-term efficacy of infliximab on background vascular leakage in patients with
      Behcet's disease.
AB  - PURPOSE: To evaluate the effect of infliximab over the initial 4 years of
      treatment on inflammatory ocular attacks and background retinal/disc vascular
      leakage in patients with refractory uveoretinitis associated with Behcet's
      disease. METHODS: Clinical records of nine patients were retrospectively
      reviewed. The main outcomes analyzed were frequency of ocular inflammatory
      attacks, background retinal and disc vascular leakage as assessed by fluorescein
      angiography during periods of clinical quiescence, best-corrected visual acuity,
      and adverse effects. RESULTS: The median follow-up on infliximab was 50 months
      (range 48-58 months). Mean frequency of attacks decreased significantly in years
      1, 2, 3, and 4 compared with the baseline 1-year period before infliximab use.
      Mean background retinal and disc vascular leakage scores also decreased
      significantly at the end of each 1-year period compared with baseline. Visual
      acuity improved or was unchanged at the end of 4 years in 17 of 18 eyes. No
      serious adverse effects were observed. CONCLUSION: Infliximab reduced the mean
      frequency of ocular attacks and mean background retinal/disc vascular leakage in
      a long-term sustained manner over 4 years of treatment in Behcet's disease
      patients.

PMID- 24946846
TI  - High intravitreal TGF-beta1 and MMP-9 levels in eyes with retinal vein occlusion.
AB  - PURPOSE: Vascular endothelial growth factor is a leading target to reduce macular
      oedema and improve visual acuity in patients with retinal vein occlusion (RVO),
      whereas the role of vascular destabilizing and fibroproliferative transforming
      growth factor (TGF)-beta1 and matrix metalloproteinases (MMP)-2 and -9 in
      pathological manifestations of RVO is anticipated but less studied. METHODS:
      Undiluted vitreous samples were collected from three central RVO and one branch
      RVO eyes, all with neovascularization and fibrosis-related sight-threatening
      complications of RVO. Undiluted vitreous samples of 40 eyes operated due to non
      ischemic condition either macular hole or pucker were used as controls. Growth
      factor and protease concentrations were measured by ELISA and gelatin zymography.
      RESULTS: Vitreous concentrations of TGF-beta1 (92.0 +/- 17.4 pg/ml vs 18.3 +/-
      27.0 pg/ml, mean +/- SD; P=0.002) and MMP-9 (847.9 +/- 1196.4 AU/ml vs 87.7 +/-
      174.0 AU/ml; P=0.010) were higher in the eyes with ischemic RVO than in the
      controls. CONCLUSIONS: High intravitreal levels of TGF-beta1 and MMP-9 are found
      in RVO eyes having neovascular and fibrosis manifestation. Further studies are
      warranted to elucidate whether targeting TGF-beta1 and MMP-9 could be beneficial
      in patients with ischemic RVO.

PMID- 24946847
TI  - Evaluation of focal choroidal excavation in the macula using swept-source optical
      coherence tomography.
AB  - PURPOSE: To evaluate imaging findings of patients with focal choroidal excavation
      (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and
      correlate it clinically. METHODS: Prospective observational case series. Eleven
      consecutive patients (12 eyes) with FCE were described. Data on demographics and
      clinical presentation were collected and imaging findings (including color
      photography, fundus autofluorescence imaging, fluorescein angiography,
      indocyanine green angiography, spectral-domain optical coherence tomography, and
      SS-OCT) were analyzed. RESULTS: The primary diagnosis was epiretinal membrane
      (two eyes), choroidal neovascularization (one eye), polypoidal choroidal
      vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry
      age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were
      conforming. One presented with a non-conforming lesion that progressed to a
      conforming lesion. One eye had multiFCE and two had two overlapping choroidal
      excavations. Using the SS-OCT, we found the choroid to be thinned out at the area
      of FCE but sclera remained normal. The choroidal tissue beneath the FCE was
      abnormal, with high internal reflectivity and poor visualization of choroidal
      vessels. There was loss of contour of the outer choroidal boundary that appeared
      to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was
      noted beneath this choroidal tissue and the choroidal-scleral interface was
      smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation
      to be stable in size. CONCLUSION: FCE can be associated with epiretinal membrane,
      central serous chorioretinopathy, and age-related macular degeneration. The
      choroid was thinned out in the area of FCE.

PMID- 24946849
TI  - Short communication: Prevalence of HIV-1 transmitted drug resistance in Liberia.
AB  - No data on HIV-transmitted drug resistance (TDR) are available in Liberia in
      which the HIV prevalence in the general population is estimated at 1.5%. The aim
      of the study was to assess the prevalence of TDR in HIV-1 from recently diagnosed
      and untreated patients living in Monrovia, Liberia. The study was performed in
      the John F. Kennedy Medical Center and in the Redemption Hospital, both located
      in Monrovia. All newly HIV-1 diagnosed patients attending voluntary counseling
      testing centers and antiretroviral therapy naive were consecutively included.
      Protease and reverse transcriptase (RT) regions sequencing was performed using
      the ANRS procedures (www.hivfrenchresistance.org). Drug resistance mutations
      (DRM) were identified according to the 2009 updated WHO surveillance DRM list.
      Among the 116 HIV-1-infected patients enrolled in the study, 85 (73%) were women.
      Protease and RT sequencing was successful in 109 (94%) and 102 (88%) samples,
      respectively. Seventy-five (66%) patients were infected with CRF02_AG. One DRM
      was observed in six samples, leading to a TDR prevalence of 5.9% (CI 95%=1.7
      10.1). DRM were observed in two patients (2.0%; CI 95%=0.0-4.7), four patients
      (3.9%; CI 95%=0.1-7.7), and one patient (0.9%; CI 95%=0.0-2.7) for nucleoside RT
      inhibitors (NRTI), non-NRTI (NNRTI), and protease inhibitors, respectively.
      Overall, one patient exhibited dual class-resistant viruses, harboring NRTI and
      NNRTI resistance mutations (1.0%; CI 95%=0.0-2.9). This first survey study in
      Liberia reported a TDR prevalence of 5.9%, classified as moderate according to
      the WHO criteria, indicating that further surveillance is warranted to follow the
      level and evolution of TDR prevalence in recently HIV-1 diagnosed patients.

PMID- 24946848
TI  - Protective effect of porphyra-334 on UVA-induced photoaging in human skin
      fibroblasts.
AB  - The significant increase in life expectancy is closely related to the growing
      interest in the impact of aging on the function and appearance of the skin. Skin
      aging is influenced by several factors, and solar ultraviolet (UV) irradiation is
      considered one of the most important causes of skin photoaging. The aim of this
      study was to examine the anti-photoaging role of porphyra-334 from Porphyra (P.)
      yezoensis, a mycosporine-like amino acid (MAA), using high-performance liquid
      chromatography (HPLC), and electrospray ionization-mass spectrometry (ESI-MS). In
      the present study, extracted UV-absorbing compounds from P. yezoensis included
      palythine, asterina-330 and porphyra-334. Porphyra-334 was the most abundant MAA
      in P. yezoensis, and it was therefore used for conducting antiphotoaging
      experiments. The effect of porphyra-334 on the prevention of photoaging was
      investigated by measuring reactive oxygen species (ROS) production and matrix
      metalloproteinase (MMP) levels, as well as extracellular matrix (ECM) components
      and protein expression in UVA-irradiated human skin fibroblasts. Porphyra-334
      suppressed ROS production and the expression of MMPs following UVA irradiation,
      while increasing levels of ECM components, such as procollagen, type I collagen,
      elastin. These results suggest that porphyra-334 has various applications in
      cosmetics and toiletries because of its anti-photoaging activities and may serve
      as a novel anti-aging agent. 

PMID- 24946850
TI  - Barriers to optimal social support in the postpartum period.
AB  - OBJECTIVE: To examine the specific barriers to mothers' realization of social
      support during the first-year postpartum. DESIGN: A qualitative approach in which
      social support data were analyzed thematically. SETTING: An urban medical center
      in Pittsburgh, Pennsylvania. PARTICIPANTS: Thirty-one women who had given birth
      in the year prior to study enrollment were recruited through posted flyers at
      multiple community sites. METHODS: Data were collected during three focus groups.
      The data that related to social support were extracted from a larger qualitative
      data set and analyzed separately for prominent social support inhibitors.
      RESULTS: Major themes that emerged were availability of trustworthy child care,
      cost of child care, demands of infant care, changing priorities, a transient
      population, and availability of family. CONCLUSIONS: Emergent barriers to social
      support such as the demands of infant care and changing priorities are likely
      challenges for women regardless of socioeconomic status. However, the volume of
      text related to availability (proximity) of family, availability of trustworthy
      child care, and the consequences of a transient lifestyle may be attributed to
      the composition of the study sample.

PMID- 24946851
TI  - Chemopreventive effect of a novel, selective TACE inhibitor on DMBA- and TPA
      induced skin carcinogenesis.
AB  - Abstract Context: Tumor necrosis factor (TNF)-alpha, a potent proinflammatory
      cytokine, plays a major role in the pathogenesis of cancer. TNF-alpha converting
      enzyme (TACE) mediates processing and release of biologically active TNF-alpha.
      OBJECTIVE: We aimed to investigate the effect of a novel, selective TACE
      inhibitor (compound 11p) on skin inflammation and associated tumorigenesis in
      mice. METHODS: Skin edema was induced in mice by dermal application 12-O
      tetradecanoylphorbol-13-acetate (TPA) solution in acetone on to the ear and the
      effect of post-treatment of compound 11p (topical application) was evaluated.
      Edema and inflammation was assessed by measuring ear thickness, weight of skin
      punch and cytokine levels. Skin cancer in mice was initiated by single topical
      application of 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by repeated TPA
      application for 20 weeks. The effect of compound 11p on papilloma incidence and
      multiplicity was evaluated. RESULTS: Treatment with compound 11p strongly
      suppressed TPA-induced elevation in skin thickness and weight. A dose-dependent
      suppression in TPA-mediated TNF-alpha, IL-6, IFN-gamma, IL-17 and PGE2 levels
      which was associated with a decrease in infiltration of inflammatory cells was
      also observed with the treatment. Moreover, compound 11p treatment delayed the
      onset, markedly reduced the papilloma incidence and multiplicity persuaded by
      DMBA and TPA. DISCUSSION AND CONCLUSION: These findings suggest that selective
      blockade of TACE suppresses TPA-induced epidermal hyperplasia, inflammatory cell
      infiltration and cytokine level. Inhibition of inflammatory events related to
      tumor growth might have led to the anti-tumor effect in mouse skin cancer model
      induced by DMBA and TPA.

PMID- 24946853
TI  - Metal oxide induced charge transfer doping and band alignment of graphene
      electrodes for efficient organic light emitting diodes.
AB  - The interface structure of graphene with thermally evaporated metal oxide layers,
      in particular molybdenum trioxide (MoO3), is studied combining photoemission
      spectroscopy, sheet resistance measurements and organic light emitting diode
      (OLED) characterization. Thin (<5 nm) MoO3 layers give rise to an 1.9 eV large
      interface dipole and a downwards bending of the MoO3 conduction band towards the
      Fermi level of graphene, leading to a near ideal alignment of the transport
      levels. The surface charge transfer manifests itself also as strong and stable p
      type doping of the graphene layers, with the Fermi level downshifted by 0.25 eV
      and sheet resistance values consistently below 50 Omega/sq for few-layer graphene
      films. The combination of stable doping and highly efficient charge
      extraction/injection allows the demonstration of simplified graphene-based OLED
      device stacks with efficiencies exceeding those of standard ITO reference
      devices.

PMID- 24946852
TI  - Identification of linear human B-cell epitopes of tick-borne encephalitis virus.
AB  - BACKGROUND: Tick-borne encephalitis (TBE) is a central nervous system infection
      transmitted to humans by ticks. The causative agent, tick-borne encephalitis
      virus (TBEV), belongs to the genus Flavivirus (family Flaviviridae), which
      includes globally important arthropod-borne viruses, such as dengue, Yellow
      fever, Japanese encephalitis and West Nile viruses. Flaviviruses are highly cross
      reactive in serological tests that are currently based on viral envelope
      proteins. The envelope (E) protein is the major antigenic determinant and it is
      known to induce neutralizing antibody responses. METHODS: We synthesized the full
      length TBEV proteome as overlapping synthetic 18-mer peptides to find dominant
      linear IgG epitopes. To distinguish natural TBEV infections from responses to TBE
      immunization or other flavivirus infections, the peptides were probed with sera
      of patients infected with TBEV, West Nile virus (WNV) or dengue virus (DENV),
      sera from TBE vaccinees and negative control sera by SPOT array technique.
      RESULTS: We identified novel linear TBEV IgG epitopes in the E protein and in the
      nonstructural protein 5 (NS5). CONCLUSIONS: In this study, we screened TBEV
      structural and nonstructural proteins to find linear epitopes specific for TBEV.
      We found 11 such epitopes and characterized specifically two of them to be
      potential for differential diagnostics. This is the first report of identifying
      dominant linear human B-cell epitopes of the whole TBEV genome. The identified
      peptide epitopes have potential as antigens for diagnosing TBEV and to
      serologically distinguish flavivirus infections from each other.

PMID- 24946854
TI  - Constructing predictive models for vaginal surgery in patients with noninvasive
      gynecological conditions.
AB  - OBJECTIVE: To develop predictive models for vaginal operative route selection
      based on clinical variables that can be easily assessed preoperatively in
      patients with noninvasive gynecological conditions. DESIGN: Retrospective study.
      SETTING: University Hospital. POPULATION: Women with routine gynecological
      surgeries via different approaches. METHODS: The medical records of 315 women
      without prolapse and undergoing hysterectomy, adnexal cystectomy or myomectomy
      were reviewed. Multiple logistic regression analysis was used to identify factors
      associated with the vaginal approach for each procedure. Predictive models were
      generated and optimal cut-off points were identified using the receiver operating
      characteristic curve. MAIN OUTCOME MEASURES: Predictive models for different
      vaginal surgical procedures. RESULTS: For hysterectomy, the patient's body mass
      index, dysmenorrheal complaints and uterine size were identified as negative
      predictors for vaginal hysterectomy, whereas previous vaginal delivery was
      positive. For adnexal cystectomy, adnexal pathology was a negative predictor,
      whereas previous vaginal delivery and ovarian cyst size were positive. For
      myomectomy, the body mass index and number of fibroids were negative predictors
      while previous vaginal delivery was positive. All three models were able to
      predict the vaginal procedures undergone by women and the areas under the curve
      were 0.88, 0.95 and 0.92, respectively. Each optimal model cut-off value
      (logit(p) = 0.53, 0.36, 0.73) resulted in good sensitivity (92.3%, 100% and
      87.5%, respectively) and specificity (77.8%, 88.6% and 90.9%, respectively).
      CONCLUSION: These predictive models, which used clinical variables that can be
      easily assessed preoperatively, may help surgeons to select candidates for
      different vaginal procedures.

PMID- 24946855
TI  - Bdellovibrio bacteriovorus HD100 guards against Pseudomonas tolaasii brown-blotch
      lesions on the surface of post-harvest Agaricus bisporus supermarket mushrooms.
AB  - BACKGROUND: Pseudomonas tolaasii is a problematic pathogen of cultured mushrooms,
      forming dark brown 'blotches' on mushroom surfaces and causing spoilage during
      crop growth and post-harvest . Treating P. tolaasii infection is difficult, as
      other, commensal bacterial species such as Pseudomonas putida are necessary for
      mushroom growth, so treatments must be relatively specific. RESULTS: We have
      found that P. tolaasii is susceptible to predation in vitro by the delta
      proteobacterium Bdellovibrio bacteriovorus. This effect also occurred in funga,
      where B. bacteriovorus was administered to post-harvest mushroom caps before and
      after administration of the P. tolaasii pathogen. A significant, visible
      improvement in blotch appearance, after incubation, was observed on
      administration of Bdellovibrio. A significant reduction in viable P. tolaasii
      cell numbers, recovered from the mushroom tissue, was detected. This was
      accompanied by a more marked reduction in blotch severity on Bdellovibrio
      administration. We found that there was in some cases an accompanying overgrowth
      of presumed-commensal, non-Pseudomonas bacteria on post-harvest mushroom caps
      after Bdellovibrio-treatment. These bacteria were identified (by 16SrRNA gene
      sequencing) as Enterobacter species, which were seemingly resistant to predation.
      We visualised predatory interactions occuring between B. bacteriovorus and P.
      tolaasii on the post-harvest mushroom cap surface by Scanning Electron
      Microscopy, seeing predatory invasion of P. tolaasii by B. bacteriovorus in
      funga. This anti-P. tolaasii effect worked well in post-harvest supermarket
      mushrooms, thus Bdellovibrio was not affected by any pre-treatment of mushrooms
      for commercial/consumer purposes. CONCLUSIONS: The soil-dwelling B. bacteriovorus
      HD100 preys upon and kills P. tolaasii, on mushroom surfaces, and could therefore
      be applied to prevent spoilage in post-harvest situations where mushrooms are
      stored and packaged for sale.

PMID- 24946856
TI  - Influence of non ionizing radiation of base stations on the activity of redox
      proteins in bovines.
AB  - BACKGROUND: The influence of electromagnetic fields on the health of humans and
      animals is still an intensively discussed and scientifically investigated issue
      (Prakt Tierarzt 11:15-20, 2003; Umwelt Medizin Gesellschaft 17:326-332, 2004; J
      Toxicol Environment Health, Part B 12:572-597, 2009). We are surrounded by
      numerous electromagnetic fields of variable strength, coming from electronic
      equipment and its power cords, from high-voltage power lines and from antennas
      for radio, television and mobile communication. Particularly the latter cause's
      controversy, as everyone likes to have good mobile reception at anytime and
      anywhere, whereas nobody wants to have such a basestation antenna in their
      proximity. RESULTS: In this experiment, the NIR has resulted in changes in the
      enzyme activities. Certain enzymes were disabled, others enabled by NIR.
      Furthermore, individual behavior patterns were observed. While certain cows
      reacted to NIR, others did not react at all, or even inversely. CONCLUSION: The
      present results coincide with the information from the literature, according to
      which NIR leads to changes in redox proteins, and that there are individuals who
      are sensitive to radiation and others that are not. However, the latter could not
      be distinctly attributed - there are cows that react clearly with one enzyme
      while they do not react with another enzyme at all, or even the inverse. The
      study approach of testing ten cows each ten times during three phases has proven
      to be appropriate. Future studies should however set the post-exposure phase
      later on.

PMID- 24946857
TI  - Circulating anti-filamin C autoantibody as a potential serum biomarker for low
      grade gliomas.
AB  - BACKGROUND: Glioma is the most common primary malignant central nervous system
      tumor in adult, and is usually not curable due to its invasive nature.
      Establishment of serum biomarkers for glioma would be beneficial both for early
      diagnosis and adequate therapeutic intervention. Filamins are an actin cross
      linker and filamin C (FLNC), normally restricted in muscle tissues, offers many
      signaling molecules an essential communication fields. Recently, filamins have
      been considered important for tumorigenesis in cancers. METHODS: We searched for
      novel glioma-associated antigens by serological identification of antigens
      utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a
      candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues)
      were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum
      anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in
      the patients with various grade gliomas. RESULTS: FLNC was expressed in glioma
      tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody
      was also detected in the serum of glioma patients, but its levels were inversely
      correlated with the tissue expression. Serum anti-FLNC autoantibody level was
      significantly higher in low-grade glioma patients than in high-grade glioma
      patients or in normal volunteers, which was confirmed in an independent
      validation set of patients' sera. The autoantibody levels in the patients with
      meningioma or cerebral infarction were at the same level of normal volunteers,
      and they were significantly lower than that of low-grade gliomas. Total IgG and
      anti-glutatione S-transferase (GST) antibody level were not altered among the
      patient groups, which suggest that the autoantibody response was specific for
      FLNC. CONCLUSIONS: The present results suggest that serum anti-FLNC autoantibody
      can be a potential serum biomarker for early diagnosis of low-grade gliomas while
      it needs a large-scale clinical study.

PMID- 24946859
TI  - An adult spindle cell rhabdomyosarcoma in the head and neck region with long-term
      survival: a case report.
AB  - INTRODUCTION: Spindle cell rhabdomyosarcoma of the head and neck is a very rare
      tumor in adults. We report on one case with long-term survival. CASE
      PRESENTATION: A 41-year-old nonsmoking Caucasian man presented in June 2007 with
      a painless swelling under his tongue. A diagnosis of a soft tissue sarcoma, and a
      myofibrosarcoma in particular, was made via biopsy. After multimodal treatment,
      including local and systemic therapy, our patient remained disease-free until
      September 2010. The local recurrence was treated unsuccessfully with various
      chemotherapy regimens. In September 2011, our patient underwent surgical
      resection again, and a spindle cell rhabdomyosarcoma was diagnosed. To analyze
      the mismatch between the original diagnosis of a myofibrosarcoma and the second
      diagnosis, the two specimens were reassessed, and a final diagnosis of a spindle
      cell rhabdomyosarcoma was made. In 2012 and 2013, our patient suffered further
      recurrences that were surgically treated, and he is still alive with disease six
      years and 10 months after the initial diagnosis in June 2007. CONCLUSIONS: In
      adults, the spindle cell rhabdomyosarcoma tumor is very rare in the head and neck
      region. In contrast to childhood tumors, spindle cell rhabdomyosarcoma in
      adulthood is often associated with a poor prognosis. In the present case, the
      radical surgical treatment might have helped to prolong the patient's overall
      survival, which has lasted more than six years. To our knowledge, this is the
      longest overall survival reported so far for this tumor entity in the head and
      neck region.

PMID- 24946858
TI  - Combining AKT inhibition with chloroquine and gefitinib prevents compensatory
      autophagy and induces cell death in EGFR mutated NSCLC cells.
AB  - Although non-small cell lung cancer (NSCLC) patients with EGFR mutation positive
      (EGFR M+) tumors initially respond well to EGFR tyrosine kinase inhibitor (TKI)
      monotherapy, the responses are usually incomplete. In this study we show that AKT
      inhibition, most importantly AKT2 inhibition, synergises with EGFR TKI inhibition
      to increase cell killing in EGFR M+ NSCLC cells. However, our data also suggest
      that the synergistic pro-apoptotic effects may be stunted due to a prosurvival
      autophagy response induced by AKT inhibition. Consequently, inhibiting autophagy
      with chloroquine significantly enhanced tumor cell death induced by gefitinib and
      AKT inhibitors in EGFR M+ cells in vitro, and produced greater tumor shrinkage in
      EGFR M+ xenografts in vivo. Together, our findings suggest that adding
      chloroquine to EGFR and AKT inhibition has the potential to improve tumor
      responses in EGFR M+ NSCLC, and that selective targeting of AKT2 may provide a
      new treatment option in NSCLC. 

PMID- 24946860
TI  - Photoinduced intramolecular electron transfer and electronic coupling
      interactions in pi- expanded imidazole derivatives.
AB  - An intramolecular excited charge transfer (CT) analysis of imidazole derivatives
      has been made. The determined electronic transition dipole moments has been used
      to estimate the electronic coupling interactions between the excited charge
      transfer singlet state ((1)CT) and the ground state (S0) or the locally excited
      state ((1)LE). The properties of excited (1)CT state imidazole derivatives have
      been exploited by the significant contribution of the electronic coupling
      interactions. The excited state intramolecular proton transfer (ESIPT) analysis
      has also been discussed. 

PMID- 24946861
TI  - Label free fluorometric characterization of DNA interaction with cholate capped
      gold nanoparticles using ethidium bromide as a fluorescent probe.
AB  - We demonstrated label free ethidium bromide assisted characterization of DNA
      interaction with cholate capped AuNPs. Interactions between ss/ds DNA and AuNPs
      with two different lengths (0.5 and 0.85 kb) were analyzed through fluorescence
      spectrophotometer and agrose gel electrophoresis analysis. Further results were
      confirmed by UV-globally visible spectrophotometer, DLS and TEM. As 0.5 and 0.85
      kb of ssDNA effectively interacted with AuNPs through the van der Waals
      interaction which consequently led to the prevention of salt induced aggregation,
      EtBr intercalations as well as fluorescence shift with less binding constant
      0.098 and 0.108 MUM, respectively. On the contrary, the same length of dsDNA (0.5
      and 0.85 kb) not interacted with AuNPs which led to the NPs aggregation, EtBr
      intercalation as well as fluorescence shift with increased binding constant 0.166
      and 0.599 MUM, respectively. This approach helped to understand the mode of
      interactions of DNA with cholate capped AuNPs without any modifications in a
      simple method and the results could be readout through the naked eye under the UV
      transilluminator. 

PMID- 24946863
TI  - New generation NMR bioreactor coupled with high-resolution NMR spectroscopy leads
      to novel discoveries in Moorella thermoacetica metabolic profiles.
AB  - An in situ nuclear magnetic resonance (NMR) bioreactor was developed and employed
      to monitor microbial metabolism under batch growth conditions in real time. We
      selected Moorella thermoacetica ATCC 49707 as a test case. M. thermoacetica
      (formerly Clostridium thermoaceticum) is a strictly anaerobic, thermophilic,
      acetogenic, gram-positive bacterium with potential for industrial production of
      chemicals. The metabolic profiles of M. thermoacetica were characterized during
      growth in batch mode on xylose (a component of lignocellulosic biomass) using the
      new generation NMR bioreactor in combination with high-resolution NMR (HR-NMR)
      spectroscopy. In situ NMR measurements were performed using water-suppressed H-1
      NMR spectroscopy at 500 MHz, and aliquots of the bioreactor contents were taken
      for 600-MHz HR-NMR spectroscopy at specific intervals to confirm metabolite
      identifications and expand metabolite coverage. M. thermoacetica demonstrated the
      metabolic potential to produce formate, ethanol, and methanol from xylose, in
      addition to its known capability of producing acetic acid. Real-time monitoring
      of bioreactor conditions showed a temporary pH decrease, with a concomitant
      increase in formic acid during exponential growth. Fermentation experiments
      performed outside of the magnet showed that the strong magnetic field employed
      for NMR detection did not significantly affect cell metabolism. Use of the in
      situ NMR bioreactor facilitated monitoring of the fermentation process, enabling
      identification of intermediate and endpoint metabolites and their correlation
      with pH and biomass produced during culture growth. Real-time monitoring of
      culture metabolism using the NMR bioreactor in combination with HR-NMR
      spectroscopy will allow optimization of the metabolism of microorganisms
      producing valuable bioproducts.

PMID- 24946864
TI  - Hydrolysis, acidification and methanogenesis during low-temperature anaerobic
      digestion of dilute dairy wastewater in an inverted fluidised bioreactor.
AB  - The application of low-temperature (10  degrees C) anaerobic digestion (LtAD) for
      the treatment of complex dairy-based wastewater in an inverted fluidised bed
      (IFB) reactor was investigated. Inadequate mixing intensity provoked poor
      hydrolysis of the substrate (mostly protein), which resulted in low chemical
      oxygen demand (COD) removal efficiency throughout the trial, averaging ~69 % at
      the best operational period. Overgrowth of the attached biomass to the support
      particles (Extendospheres) induced bed stratification by provoking agglutination
      of the particles and supporting their washout by sedimentation, which contributed
      to unstable bioprocess performance at the organic loading rates (OLRs) between
      0.5 and 5 kg COD m(-3) day(-1). An applied OLR above 2 kg COD m(-3) day(-1)
      additionally promoted acidification and strongly influenced the microbial
      composition and dynamics. Hydrogenotrophic methanogens appeared to be the mostly
      affected group by the Extendospheres particle washout as a decrease in their
      abundance was observed by quantitative PCR analysis towards the end of the trial,
      although the specific methanogenic activity and maximum substrate utilisation
      rate on H2/CO2 indicated high metabolic activity and preference towards
      hydrogenotrophic methanogenesis of the reactor biomass at this stage. The
      bacterial community in the bioreactor monitored via denaturing gradient gel
      electrophoresis (DGGE) also suggested an influence of OLR stress on bacterial
      community structure and population dynamics. The data presented in this work can
      provide useful information in future optimisation of fluidised reactors intended
      for digestion of complex industrial wastewaters during LtAD.

PMID- 24946862
TI  - Cinnamon treatment upregulates neuroprotective proteins Parkin and DJ-1 and
      protects dopaminergic neurons in a mouse model of Parkinson's disease.
AB  - Upregulation and/or maintenance of Parkinson's disease (PD)-related beneficial
      proteins such as Parkin and DJ-1 in astrocytes during neurodegenerative insults
      may have therapeutic efficacy in PD. Cinnamon is a commonly used natural spice
      and flavoring material throughout the world. Here we have explored a novel use of
      cinnamon in upregulating Parkin and DJ-1 and protecting dopaminergic neurons in
      MPTP mouse model of PD. Recently we have delineated that oral feeding of cinnamon
      (Cinnamonum verum) powder produces sodium benzoate (NaB) in blood and brain of
      mice. Proinflammatory cytokine IL-1beta decreased the level of Parkin/DJ-1 in
      mouse astrocytes. However, cinnamon metabolite NaB abrogated IL-1beta-induced
      loss of these proteins. Inability of TNF-alpha to produce nitric oxide (NO) and
      decrease the level of Parkin/DJ-1 in wild type (WT) astrocytes, failure of IL
      1beta to reduce Parkin/DJ-1 in astrocytes isolated from iNOS (-/-) mice, and
      decrease in Parkin/DJ-1 in WT astrocytes by NO donor DETA-NONOate suggest that NO
      is a negative regulator of Parkin/DJ-1. Furthermore, suppression of IL-1beta
      induced expression of iNOS in astrocytes by NaB and reversal of NaB-mediated
      protection of Parkin/DJ-1 by DETA-NONOate in astrocytes indicate that NaB
      protects Parkin/DJ-1 in activated astrocytes via suppressing iNOS. Similarly MPTP
      intoxication also increased the level of iNOS and decreased the level of
      Parkin/DJ-1 in vivo in the nigra. However, oral treatment of MPTP-intoxicated
      mice with cinnamon powder and NaB reduced the expression of iNOS and protected
      Parkin/DJ-1 in the nigra. These findings paralleled dopaminergic neuronal
      protection, normalized striatal neurotransmitters, and improved motor functions
      by cinnamon in MPTP-intoxicated mice. These results suggest that cinnamon may be
      beneficial for PD patients. 

PMID- 24946865
TI  - Characterization of an extensin-modifying metalloprotease: N-terminal processing
      and substrate cleavage pattern of Pectobacterium carotovorum Prt1.
AB  - Compared to other plant cell wall-degrading enzymes, proteases are less well
      understood. In this study, the extracellular metalloprotease Prt1 from
      Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in
      Escherichia coli and characterized with respect to N-terminal processing, thermal
      stability, substrate targets, and cleavage patterns. Prt1 is an autoprocessing
      protease with an N-terminal signal pre-peptide and a pro-peptide which has to be
      removed in order to activate the protease. The sequential cleavage of the N
      terminus was confirmed by mass spectrometry (MS) fingerprinting and N-terminus
      analysis. The optimal reaction conditions for the activity of Prt1 on azocasein
      were at pH 6.0, 50  degrees C. At these reaction conditions, K M was 1.81 mg/mL
      and k cat was 1.82 * 10(7) U M(-1). The enzyme was relatively stable at 50 
      degrees C with a half-life of 20 min. Ethylenediaminetetraacetic acid (EDTA)
      treatment abolished activity; Zn(2+) addition caused regain of the activity, but
      Zn(2+)addition decreased the thermal stability of the Prt1 enzyme presumably as a
      result of increased proteolytic autolysis. In addition to casein, the enzyme
      catalyzed degradation of collagen, potato lectin, and plant extensin. Analysis of
      the cleavage pattern of different substrates after treatment with Prt1 indicated
      that the protease had a substrate cleavage preference for proline in substrate
      residue position P1 followed by a hydrophobic residue in residue position P1' at
      the cleavage point. The activity of Prt1 against plant cell wall structural
      proteins suggests that this enzyme might become an important new addition to the
      toolbox of cell-wall-degrading enzymes for biomass processing.

PMID- 24946866
TI  - Multiple-object tracking while driving: the multiple-vehicle tracking task.
AB  - Many contend that driving an automobile involves multiple-object tracking. At
      this point, no one has tested this idea, and it is unclear how multiple-object
      tracking would coordinate with the other activities involved in driving. To
      address some of the initial and most basic questions about multiple-object
      tracking while driving, we modified the tracking task for use in a driving
      simulator, creating the multiple-vehicle tracking task. In Experiment 1, we
      employed a dual-task methodology to determine whether there was interference
      between tracking and driving. Findings suggest that although it is possible to
      track multiple vehicles while driving, driving reduces tracking performance, and
      tracking compromises headway and lane position maintenance while driving.
      Modified change-detection paradigms were used to assess whether there were change
      localization advantages for tracked targets in multiple-vehicle tracking. When
      changes occurred during a blanking interval, drivers were more accurate
      (Experiment 2a) and ~250 ms faster (Experiment 2b) at locating the vehicle that
      changed when it was a target rather than a distractor in tracking. In a more
      realistic driving task where drivers had to brake in response to the sudden onset
      of brake lights in one of the lead vehicles, drivers were more accurate at
      localizing the vehicle that braked if it was a tracking target, although there
      was no advantage in terms of braking response time. Overall, results suggest that
      multiple-object tracking is possible while driving and perhaps even advantageous
      in some situations, but further research is required to determine whether
      multiple-object tracking is actually used in day-to-day driving.

PMID- 24946867
TI  - Something from (almost) nothing: buildup of object memory from forgettable single
      fixations.
AB  - We can recognize thousands of individual objects in scores of familiar settings,
      and yet we see most of them only through occasional glances that are quickly
      forgotten. How do we come to recognize any of these objects? Here, we show that
      when objects are presented intermittently for durations of single fixations, the
      originally fleeting memories become gradually stabilized, such that, after just
      eight separated fixations, recognition memory after half an hour is as good as
      during an immediate memory test. However, with still shorter presentation
      durations, memories take more exposures to stabilize. Our results thus suggest
      that repeated glances suffice to remember the objects of our environment. 

PMID- 24946869
TI  - Decreased tricuspid regurgitation following percutaneous closure of congenital
      perimembranous ventricular septal defect: immediate and 6-month echocardiographic
      assessment.
AB  - As a common concomitant performance and the most frequent complications of
      transcatheter perimembranous ventricular septal defect (VSD) closure, tricuspid
      regurgitation (TR) has rarely been concerned. From January 2008 to December 2012,
      a total of 70 patients (men: 33, women: 37; mean age: 30.0 +/- 17.1 years) with
      at least mild TR before VSD closure were examined in 508 consecutive congenital
      perimembranous VSD patients to investigate the outcomes of TR. After VSD closure,
      the jet area decreased from 3.4 +/- 2.5 to 1.2 +/- 2.5 cm(2) (p < 0.001);
      however, no significant decrease was found in 3 patients (mean age 59.7 +/- 2.5
      years) with severe TR (12.0 +/- 1.2 versus 11.2 +/- 3.2 cm(2), p = 0.668).
      Compared to the early outcome after VSD closure, the jet area detected by TTE at
      6-month follow-up had further decreased (1.2 +/- 2.5 versus 0.9 +/- 2.2 cm(2), p
      < 0.001). In 6 patients, a slight residual shunt was detected immediately after
      VSD closure and diminished in 3 patients at 6-month follow-up. The hemolysis
      occurred in one of these six patients and recovered after 3 days. In conclusion,
      functional TR was ameliorated after percutaneous VSD closure, although persistent
      abundant TR was common in patients with severe TR before procedure. 

PMID- 24946871
TI  - Cerebral blood volume and vasodilation are independently diminished by aging and
      hypertension: a near infrared spectroscopy study.
AB  - BACKGROUND: Senescent changes in brain microvascular circulation may cause or
      contribute to age-related cognitive decline. Such changes are promoted partly by
      aging, but also by chronic hypertension, a leading treatable cause of cognitive
      decline. OBJECTIVES: We aimed to non-invasively detect in vivo the senescent
      changes in brain microvascular circulation associated with age and hypertension,
      and inquired whether decrements driven by aging would be exacerbated by chronic
      hypertension. METHODS: In this longitudinal study, absolute near infrared
      spectroscopy (NIRS) was used to quantify in vivo cerebral blood volume (CBV) and
      assess the hemodynamic response to a hypercapnic respiratory challenge in
      normotensive Wistar-Kyoto (WKY) and spontaneous-hypertensive (SHR) rats. The
      impact of age and hypertension were evaluated by repeating these measurements on
      the same animals at 4- and 16-months of age. RESULTS: CBV decreased markedly with
      age in both strains, from 4.5 +/- 0.2 to 2.6 +/- 0.1 ml/100g tissue, on average.
      Chronic hypertension, however, did not significantly exacerbate this age-related
      decrease in CBV (-48.1 +/- 3.7% in WKYs versus -53.3 +/- 5.4% in SHRs). In
      contrast, vasoreactivity was already impaired in the young hypertensive rats
      (DeltaVMR 0.017 +/- 0.014 in young SHRs versus 0.042 +/- 0.005 in young WKYs) and
      further worsened by middle-age (DeltaVMR 0.011 +/- 0.017 middle-aged SHRs).
      CONCLUSION: Whereas a decrease in brain blood volume correlated with age but not
      hypertension, vasodilatory capacity was diminished due to hypertension but did
      not appear affected by age alone. The ability of absolute NIRS to distinguish
      between such senescent changes in brain (micro)vascular circulation in life may
      allow early detection and intervention to preserve cerebrovascular health with
      age.

PMID- 24946872
TI  - Type-1 cannabinoid receptor activity during Alzheimer's disease progression.
AB  - The activity of CB1 cannabinoid receptors was studied in postmortem brain samples
      of Alzheimer's disease (AD) patients during clinical deterioration. CB1 activity
      was higher at earlier AD stages in limited hippocampal areas and internal layers
      of frontal cortex, but a decrease was observed at the advanced stages. The
      pattern of modification appears to indicate initial hyperactivity of the
      endocannabinoid system in brain areas that lack classical histopathological
      markers at earlier stages of AD, indicating an attempt to compensate for the
      initial synaptic impairment, which is then surpassed by disease progression.
      These results suggest that initial CB1 stimulation might have therapeutic
      relevance. 

PMID- 24946873
TI  - Golgi apparatus and protein trafficking in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive degeneration of the brain, inducing
      memory decline, inability in learning, and behavioral alterations, resulting
      progressively in a marked deterioration of all mental activities and eventually a
      vegetative state. The main causative factor, however, is still unclear. The
      implication of amyloid-beta, AbetaPP, tau protein, the selective loss of neurons,
      the alteration of the synapses, the cytoskeletal changes, and the morphological
      alterations of the brain capillaries contribute substantially to the pathogenetic
      profile of the disease, without sufficiently enlightening the initial steps of
      the pathological procedures. The ultrastructure of the neuronal organelles as
      well as histochemical studies revealed substantial alterations, primarily
      concerning mitochondria. In this study, the morphological and morphometric
      alterations of the Golgi apparatus (GA) are described in the Purkinje cells of
      the cerebellum in twenty AD brains, studied with electron microscopy. As it is
      well established, GA has a very important role to play in many procedures such as
      glycosylation, sulfation, and proteolysis of protein systems, which are
      synthesized in the endoplasmic reticulum of nerve cells and glia. GA may also
      play a crucial role in protein trafficking and in misfolding of protein
      aggregates. In addition, the hyperphosphorylation of tau protein is closely
      related with the pathology of GA. In AD cases, described in this study, an
      obvious fragmentation of the cisternae of GA was observed in the Purkinje cells
      of the vermis and the cerebellar hemispheres. This alteration of GA may be
      associated with alterations of microtubules, impaired protein trafficking, and
      dendritic, spinal, and synaptic pathology, since protein trafficking plays an
      essential role in the three dimensional organization of the dendritic arbor and
      in the integrity of the synaptic components. 

PMID- 24946870
TI  - Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U
      RNA editing in mouse small intestine and liver.
AB  - BACKGROUND: RNA editing encompasses a post-transcriptional process in which the
      genomically templated sequence is enzymatically altered and introduces a modified
      base into the edited transcript. Mammalian C-to-U RNA editing represents a
      distinct subtype of base modification, whose prototype is intestinal
      apolipoprotein B mRNA, mediated by the catalytic deaminase Apobec-1. However, the
      genome-wide identification, tissue-specificity and functional implications of
      Apobec-1-mediated C-to-U RNA editing remain incompletely explored. RESULTS: Deep
      sequencing, data filtering and Sanger-sequence validation of intestinal and
      hepatic RNA from wild-type and Apobec-1-deficient mice revealed 56 novel editing
      sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs, all within 3'
      untranslated regions. Eleven of 17 liver RNAs shared editing sites with
      intestinal RNAs, while 6 sites are unique to liver. Changes in RNA editing lead
      to corresponding changes in intestinal mRNA and protein levels for 11 genes.
      Analysis of RNA editing in vivo following tissue-specific Apobec-1 adenoviral or
      transgenic Apobec-1 overexpression reveals that a subset of targets identified in
      wild-type mice are restored in Apobec-1-deficient mouse intestine and liver
      following Apobec-1 rescue. We find distinctive polysome profiles for several RNA
      editing targets and demonstrate novel exonic editing sites in nuclear
      preparations from intestine but not hepatic apolipoprotein B RNA. RNA editing is
      validated using cell-free extracts from wild-type but not Apobec-1-deficient
      mice, demonstrating that Apobec-1 is required. CONCLUSIONS: These studies define
      selective, tissue-specific targets of Apobec-1-dependent RNA editing and show the
      functional consequences of editing are both transcript- and tissue-specific.

PMID- 24946874
TI  - Aberrant functional networks connectivity and structural atrophy in silent
      lacunar infarcts: relationship with cognitive impairments.
AB  - Silent or asymptomatic lacunar infarcts (LACI) are common in elderly individuals,
      but it remains largely unclear how these often neglected silent brain infarcts
      lead to multiple domain cognitive deficits and even Alzheimer's disease (AD). In
      this study, we investigated the difference between patients with silent LACI in
      basal ganglia region and healthy controls for the structural and functional
      changes in the aspects of alterations of gray matter (GM) volume and intra-/inter
      default mode network (DMN) and salience network (SN) connectivity. Thirty
      patients with silent LACI in the basal ganglia region and thirty healthy controls
      participated in the study. Voxel-based morphometry analysis was employed to
      measure the GM volume. We further investigated the intra/inter-network
      connectivity of DMN and SN using resting-state functional magnetic resonance
      imaging. Compared with healthy controls, patients performed worse in cognitive
      function in the aspects of general mental status, attention, and memory. The
      LACIs showed more severe GM atrophy in insula, anterior cingulate cortex,
      caudate, and superior temporal pole than controls. The connectivity within and
      between two networks was also reduced in patients. Importantly, the disrupted
      connectivity correlated with the patients' cognitive performance. Our findings
      support the hypothesis that silent lacunar infarcts result in cognitive decline,
      GM, and functional connectivity loss.

PMID- 24946876
TI  - Depression in Alzheimer's disease: epidemiology, mechanisms, and management.
AB  - Depression occurs with a high prevalence of up to 50% in patients with
      Alzheimer's disease (AD) and increases the caregivers' burden. Depression
      symptoms can precede clinical diagnosis of AD for years or occurs around the
      onset of AD, although the etiology and pathologic mechanism of depression in AD
      pathogenesis remain unclear. Here, we provide an overview on recent studies,
      indicating that genetic factors, neuroanatomic changes, vascular risk factors,
      and the imbalance of neurotransmitters might contribute to depressive symptoms in
      AD. Tau pathology and amyloid-beta accumulation also correlate with depression in
      AD. In addition, the alteration of hypothalamic-pituitary-adrenal axis,
      inflammatory pathway, and neurotrophin deficiency are the possible biological
      mechanisms linking depression and AD, and might become the potential targets for
      AD treatment. Current data support that antidepressants are promising to
      alleviate the symptom, though the efficacy is controversial. Moreover,
      antidementia medication and non-pharmacological interventions can be potential
      choices. In this review, we describe the prevalence and clinical course of
      depression in AD, analyze the underlying mechanisms, and discuss the possible
      management strategies for depression in patients with AD.

PMID- 24946875
TI  - Oral inflammation, tooth loss, risk factors, and association with progression of
      Alzheimer's disease.
AB  - Periodontitis is a polymicrobial chronic inflammatory disease of tooth-supporting
      tissues with bacterial etiology affecting all age groups, becoming chronic in a
      subgroup of older individuals. Periodontal pathogens Porphyromonas gingivalis,
      Tannerella forsythia, and Treponema denticola are implicated in the development
      of a number of inflammatory pathologies at remote organ sites, including
      Alzheimer's disease (AD). The initial inflammatory hypothesis proposed that AD
      hallmark proteins were the main contributors of central nervous system (CNS)
      inflammation. This hypothesis is expanding to include the role of infections,
      lifestyle, and genetic and environmental factors in the pathogenesis of AD.
      Periodontal disease (PD) typifies a condition that encompasses all of the above
      factors including pathogenic bacteria. These bacteria not only are the source of
      low-grade, chronic infection and inflammation that follow daily episodes of
      bacteremia arising from everyday tasks such as brushing, flossing teeth, chewing
      food, and during dental procedures, but they also disseminate into the brain from
      closely related anatomical pathways. The long-term effect of inflammatory
      mediators, pathogens, and/or their virulence factors, reaching the brain
      systemically or otherwise would, over time, prime the brain's own microglia in
      individuals who have inherent susceptibility traits. Such susceptibilities
      contribute to inadequate neutralization of invading agents, upon reaching the
      brain. This has the capacity to create a vicious cycle of sustained local
      inflammatory milieu resulting in the loss of cytoarchitectural integrity and
      vital neurons with subsequent loss of function (deterioration in memory). The
      possible pathways between PD and AD development are considered here, as well as
      environmental factors that may modulate/exacerbate AD symptoms. 

PMID- 24946877
TI  - Correlation between interaction strengths drives stability in large ecological
      networks.
AB  - Food webs have markedly non-random network structure. Ecologists maintain that
      this non-random structure is key for stability, since large random ecological
      networks would invariably be unstable and thus should not be observed
      empirically. Here we show that a simple yet overlooked feature of natural food
      webs, the correlation between the effects of consumers on resources and those of
      resources on consumers, substantially accounts for their stability. Remarkably,
      random food webs built by preserving just the distribution and correlation of
      interaction strengths have stability properties similar to those of the
      corresponding empirical systems. Surprisingly, we find that the effect of
      topological network structure on stability, which has been the focus of countless
      studies, is small compared to that of correlation. Hence, any study of the
      effects of network structure on stability must first take into account the
      distribution and correlation of interaction strengths. 

PMID- 24946878
TI  - A global assembly of adult female mosquito mark-release-recapture data to inform
      the control of mosquito-borne pathogens.
AB  - BACKGROUND: Pathogen transmission by mosquitos is known to be highly sensitive to
      mosquito bionomic parameters. Mosquito mark-release-recapture (MMRR) experiments
      are a standard method for estimating such parameters including dispersal,
      population size and density, survival, blood feeding frequency and blood meal
      host preferences. METHODS: We assembled a comprehensive database describing adult
      female MMRR experiments. Bibliographic searches were used to build a digital
      library of MMRR studies and selected data describing the reported outcomes were
      extracted. RESULTS: The resulting database contained 774 unique adult female MMRR
      experiments involving 58 vector mosquito species from the three main genera of
      importance to human health: Aedes, Anopheles and Culex. Crude examination of
      these data revealed patterns associated with geography as well as mosquito genus,
      consistent with bionomics varying by species-specific life history and ecological
      context. Recapture success varied considerably and was significantly different
      amongst genera, with 8, 4 and 1% of adult females recaptured for Aedes, Anopheles
      and Culex species, respectively. A large proportion of experiments (59%)
      investigated dispersal and survival and many allowed disaggregation of the
      release and recapture data. Geographic coverage was limited to just 143
      localities around the world. CONCLUSIONS: This MMRR database is a substantial
      contribution to the compilation of global data that can be used to better inform
      basic research and public health interventions, to identify and fill knowledge
      gaps and to enrich theory and evidence-based ecological and epidemiological
      studies of mosquito vectors, pathogen transmission and disease prevention. The
      database revealed limited geographic coverage and a relative scarcity of
      information for vector species of substantial public health relevance. It
      represents, however, a wealth of entomological information not previously
      compiled and of particular interest for mosquito-borne pathogen transmission
      models.

PMID- 24946879
TI  - Sympathoactivation and rho-kinase-dependent baroreflex function in experimental
      renovascular hypertension with reduced kidney mass.
AB  - BACKGROUND: Dysregulation of the autonomic nervous system is frequent in subjects
      with cardiovascular disease. The contribution of different forms of renovascular
      hypertension and the mechanisms contributing to autonomic dysfunction in
      hypertension are incompletely understood. Here, murine models of renovascular
      hypertension with preserved (2-kidneys-1 clip, 2K1C) and reduced (1-kidney-1
      clip, 1K1C) kidney mass were studied with regard to autonomic nervous system
      regulation (sympathetic tone: power-spectral analysis of systolic blood pressure;
      parasympathetic tone: power-spectral analysis of heart rate) and baroreflex
      sensitivity of heart rate by spontaneous, concomitant changes of systolic blood
      pressure and pulse interval. Involvement of the renin-angiotensin system and the
      rho-kinase pathway were determined by application of inhibitors. RESULTS: C57BL6N
      mice (6 to 11) with reduced kidney mass (1K1C) or with preserved kidney mass
      (2K1C) developed a similar degree of hypertension. In comparison to control mice,
      both models presented with a significantly increased sympathetic tone and lower
      baroreflex sensitivity of heart rate. However, only 2K1C animals had a lower
      parasympathetic tone, whereas urinary norepinephrine excretion was reduced in the
      1K1C model. Rho kinase inhibition given to a subset of 1K1C and 2K1C animals
      improved baroreflex sensitivity of heart rate selectively in the 1K1C model. Rho
      kinase inhibition had no additional effects on autonomic nervous system in either
      model of renovascular hypertension and did not change the blood pressure.
      Blockade of AT1 receptors (in 2K1C animals) normalized the sympathetic tone,
      decreased resting heart rate, improved baroreflex sensitivity of heart rate and
      parasympathetic tone. CONCLUSIONS: Regardless of residual renal mass, blood
      pressure and sympathetic tone are increased, whereas baroreflex sensitivity is
      depressed in murine models of renovascular hypertension. Reduced norepinephrine
      excretion and/or degradation might contribute to sympathoactivation in
      renovascular hypertension with reduced renal mass (1K1C). Overall, the study
      helps to direct research to optimize medical therapy of hypertension.

PMID- 24946880
TI  - Automated peptide mapping and protein-topographical annotation of proteomics
      data.
AB  - BACKGROUND: In quantitative proteomics, peptide mapping is a valuable approach to
      combine positional quantitative information with topographical and domain
      information of proteins. Quantitative proteomic analysis of cell surface shedding
      is an exemplary application area of this approach. RESULTS: We developed
      ImproViser ( http://www.improviser.uni-freiburg.de) for fully automated peptide
      mapping of quantitative proteomics data in the protXML data. The tool generates
      sortable and graphically annotated output, which can be easily shared with
      further users. As an exemplary application, we show its usage in the proteomic
      analysis of regulated intramembrane proteolysis. CONCLUSION: ImproViser is the
      first tool to enable automated peptide mapping of the widely-used protXML format.

PMID- 24946881
TI  - WRKY41 controls Arabidopsis seed dormancy via direct regulation of ABI3
      transcript levels not downstream of ABA.
AB  - Although seed dormancy is an important agronomic trait, its molecular basis is
      poorly understood. ABSCISIC ACID INSENSITIVE 3 (ABI3) plays an essential role in
      the establishment of seed dormancy. Here, we show that the lack of a seed
      expressed WRKY transcription factor, WRKY41, confers reduced primary seed
      dormancy and thermoinhibition, phenotypes resembling those for a lack of ABI3.
      Loss-of-function abi3-17 and wrky41 alleles also both confer reduced sensitivity
      to ABA during germination and early seedling growth. Absence of WRKY41 decreases
      ABI3 transcript abundance in maturing and imbibed seeds, whereas transgenically
      overexpressing WRKY41 increases ABI3 expression. Moreover, transgenic
      overexpression of ABI3 completely restores seed dormancy phenotypes on wrky41.
      ChIP-qPCR and EMSA reveal that WRKY41 binds directly to the ABI3 promoter through
      three adjacent W-boxes, and a transactivation assay indicates that these W-boxes
      are essential for ABI3 expression. Whilst RT-qPCR analysis shows that the
      regulation of ABI3 by WRKY41 is not through ABA and other factors known to
      promote ABI3 transcription during seed maturation and germination, we also show
      that high concentrations of ABA might promote negative feedback regulation of
      WRKY41 expression. Finally, analysis of the wrky41 aba2 double mutant confirms
      that WRKY41 and ABA collaboratively regulate ABI3 expression and seed dormancy.
      In summary, our results demonstrate that WRKY41 is an important regulator of ABI3
      expression, and hence of seed dormancy. 

PMID- 24946882
TI  - What's in this issue?

PMID- 24946883
TI  - Moving from crisis intervention towards person-centredness.

PMID- 24946884
TI  - Critical care nursing and older people - is there an issue?

PMID- 24946890
TI  - Critical care nursing in Mburara, Uganda.

PMID- 24946892
TI  - Accuracy of initial critical care triage decisions in blast versus non-blast
      trauma.
AB  - ABSTRACT OBJECTIVE: We investigated the accuracy of initial critical care triage
      in blast-injured versus non-blast-injured trauma patients, focusing on those
      inappropriately triaged to the intensive care unit (ICU) for brief (<16 h) stays.
      METHODS: We conducted a retrospective review of the Israel National Trauma
      Registry, applying a predetermined definition of need for initial ICU admission.
      RESULTS: A total of 883 blast-injured and 112 185 non-blast-injured patients were
      categorized according to their need for ICU admission. Of these admissions, 5.7%
      in the blast setting and 8.4% in the non-blast setting were considered
      unnecessary. The sensitivity, specificity, and positive and negative likelihood
      ratios for the triage officers' decisions in assigning patients to the ICU were
      95.5%, 98.8%, 77.2, and 0.05, respectively, in the blast setting, and 91.2%,
      99.5%, 200.5, and 0.09, respectively, in the non-blast setting. CONCLUSIONS:
      Triage officers do a better job sending to the ICU only those patients who
      require initial intensive care in the non-blast setting, though this is obscured
      by a much greater overall need for ICU-level care in the blast setting.
      Implementing triage protocols in the blast setting may help reduce the number of
      patients sent initially to the ICU for brief periods, thus increasing the
      availability of this resource.

PMID- 24946893
TI  - Controlled nanometric fibers of self-assembled designed protein scaffolds.
AB  - The use of biological molecules as platforms for templating and nanofabrication
      is an emerging field. Here, we use designed protein building blocks based on
      small repetitive units (consensus tetratricopeptide repeat - CTPR) to generate
      fibrillar linear nanostructures by controlling the self-assembly properties of
      the units. We fully characterize the kinetics and thermodynamics of the assembly
      and describe the polymerization process by a simple model that captures the
      features of the structures formed under defined conditions. This work, together
      with previously established functionalization potential, sets up the basis for
      the application of these blocks in the fabrication and templating of complex
      hybrid nanostructures. 

PMID- 24946894
TI  - The structure of a PII signaling protein from a halophilic archaeon reveals novel
      traits and high-salt adaptations.
AB  - To obtain insights into archaeal nitrogen signaling and haloadaptation of the
      nitrogen/carbon/energy-signaling protein PII, we determined crystal structures of
      recombinantly produced GlnK2 from the extreme halophilic archaeon Haloferax
      mediterranei, complexed with AMP or with the PII effectors ADP or ATP, at
      respective resolutions of 1.49 A, 1.45 A, and 2.60 A. A unique trait of these
      structures was a three-tongued crown protruding from the trimer body convex side,
      formed by an 11-residue, N-terminal, highly acidic extension that is absent from
      structurally studied PII proteins. This extension substantially contributed to
      the very low pI value, which is a haloadaptive trait of H. mediterranei GlnK2,
      and participated in hexamer-forming contacts in one crystal. Similar acidic N
      extensions are shown here to be common among PII proteins from halophilic
      organisms. Additional haloadaptive traits prominently represented in H.
      mediterranei GlnK2 are a very high ratio of small residues to large hydrophobic
      aliphatic residues, and the highest ratio of polar to nonpolar exposed surface
      for any structurally characterized PII protein. The presence of a dense hydration
      layer in the region between the three T-loops might also be a haloadaptation.
      Other unique findings revealed by the GlnK2 structure that might have functional
      relevance are: the adoption by its T-loop of a three-turn alpha-helical
      conformation, perhaps related to the ability of GlnK2 to directly interact with
      glutamine synthetase; and the firm binding of AMP, confirmed by biochemical
      binding studies with ATP, ADP, and AMP, raising the possibility that AMP could be
      an important PII effector, at least in archaea. DATABASE: The atomic coordinates
      and structure factors have been deposited in the Protein Data Bank under the
      accession numbers 4OZL (hmGlnK2-AMP), 4OZJ (hmGlnK2-ADP), and 4OZN (hmGlnK2-ATP).
      STRUCTURED DIGITAL ABSTRACT: hmGlnK2 and hmGlnK2 bind by x-ray crystallography
      (View interaction).

PMID- 24946896
TI  - Editorial: Acknowledging complexity and heterogeneity in causality--implications
      of recent insights into neuropsychology of childhood disorders for clinical
      practice.
AB  - From a clinical perspective research that tries to unravel the causal processes
      that underpin mental health problems can often seem esoteric and far removed from
      day to day clinical decision making. Indeed even though there are now a plethora
      of evidence based clinical guidelines that aim to support the translational
      process it still takes many years for new scientific understanding of a condition
      to permeate routine clinical practice, via this route. At the same time, however,
      a clinician's personal and informal interpretation of what is causing their
      patients' problems can have very important clinical implications and impact
      directly on; their formulation of a patient's presentation, the way in which they
      transmit this to the patient and their family and any treatment decisions that
      are made. Clinicians who are able to stay up to date with the latest evidence and
      scientific debate about what is and is not known about the underlying causes of
      mental health problems should be at an advantage in this regard. But for the busy
      clinician, 'just' staying up to date with the huge amount of new directly related
      to this topic is in itself a big ask in itself - critically appraising this
      evidence, in a balanced way, another thing altogether. To facilitate this process
      it is necessary for researchers to make every effort to include a balanced, clear
      and relevant discussion of the translational implications of their findings. In
      particular they must try to avoid overselling a message that may attract a lot of
      initial attention but that may, in time, prove to be a false dawn or an over
      simplification. 

PMID- 24946895
TI  - Biophysical parameters during radiofrequency catheter ablation of scar-mediated
      ventricular tachycardia: epicardial and endocardial applications via manual and
      magnetic navigation.
AB  - BACKGROUND: There is a paucity of data on biophysical parameters during
      radiofrequency ablation of scar-mediated ventricular tachycardia (VT). METHODS
      AND RESULTS: Data were collected from consecutive patients undergoing VT ablation
      with open-irrigation. Complete data were available for 372 lesions in 21
      patients. The frequency of biophysical parameter changes were: >10Omega reduction
      (80%), bipolar EGM reduction (69%), while loss of capture was uncommon (32%).
      Unipolar injury current was seen in 72% of radiofrequency applications. Both EGM
      reduction and impedance drop were seen in 57% and a change in all 3 parameters
      was seen in only 20% of lesions. Late potentials were eliminated in 33%,
      reduced/modified in 56%, and remained after ablation in 11%. Epicardial lesions
      exhibited an impedance drop (90% vs. 76%, P = 0.002) and loss of capture (46% vs.
      27%, P < 0.001) more frequently than endocardial lesions. Lesions delivered
      manually exhibited a >10Omega impedance drop (83% vs. 71%, P = 0.02) and an EGM
      reduction (71% vs. 40%, P < 0.001) more frequently than lesions applied using
      magnetic navigation, although loss of capture, elimination of LPs, and a change
      in all 3 parameters were similarly observed. CONCLUSIONS: VT ablation is
      inefficient as the majority of radiofrequency lesions do not achieve more than
      one targeted biophysical parameter. Only one-third of RF applications targeted at
      LPs result in complete elimination. Epicardial ablation within scar may be more
      effective than endocardial lesions, and lesions applied manually may be more
      effective than lesions applied using magnetic navigation. New technologies
      directed at identifying and optimizing ablation effectiveness in scar are
      clinically warranted.

PMID- 24946897
TI  - Commentary: Improving treatment for youth with callous-unemotional traits through
      the intersection of basic and applied science--reflections on Dadds et al.
      (2014).
AB  - There is increasing evidence that callous-unemotional (CU) traits delineate a
      distinctive group of youth with antisocial behavior (AB). While controversies
      surrounding the construct of CU traits remain, the Dadds et al. (2014) study in
      this issue is emblematic of recent research that has focused on understanding the
      development of CU traits among antisocial youth. We explore four pertinent issues
      in the study of youth AB highlighted by this study, and highlight this study as
      exemplar research program that will ultimately help youth and families through
      translation from the lab to the clinic.

PMID- 24946898
TI  - Where the wild things are: looking for uncultured Glomeromycota.
AB  - Our knowledge of Glomeromycotan fungi rests largely on studies of cultured
      isolates. However, these isolates probably comprise one life-history strategy -
      ruderal. Consequently, our knowledge of arbuscular mycorrhizal (AM) fungi may be
      biased towards fungi that occur primarily in disturbed habitats and associate
      with disturbance-tolerant host plants. We can expect to see a signal for this in
      DNA-based community surveys: human-impacted habitats and cultivated plants should
      yield a higher proportion of AM fungal species that have been cultured compared
      with natural habitats and wild plants. Using the MaarjAM database (a curated open
      access database of Glomeromycotan sequences), we performed a meta-analysis on
      studies that described AM fungal communities from a variety of habitats and host
      plants. We found a greater proportion of cultured AM fungal taxa in human
      impacted habitats. In particular, undisturbed forests and grasslands/savannahs
      contained significantly fewer cultured taxa than human-impacted sites. We also
      found that wild plants hosted fewer cultured fungal taxa than cultivated plants.
      Our data show that natural communities of AM fungi are composed largely of
      uncultured taxa, and this is particularly pronounced in natural habitats and wild
      plants. We are better poised to understand the functioning of AM symbioses
      associated with cultivated plants and human-impacted habitats. 

PMID- 24946899
TI  - Graphene oxide-rare earth metal-organic framework composites for the selective
      isolation of hemoglobin.
AB  - Graphene oxide-La(BTC)(H2O)6 (H3BTC=1,3,5-benzenetricarboxylic acid) metal
      organic framework composites (LaMOF-GOn, n = 1-6, corresponding to the percentage
      of GO at 1, 2, 3, 4, 5, and 10%) are prepared through a simple and large-scale
      method at room temperature. The obtained composites are characterized by ATR-FTIR
      spectra, SEM, XRD, TGA, and N2 adsorption-desorption isotherm. The presence of GO
      significantly changes the morphologies of the composites from spindly rectangular
      rods to irregular thick blocks and increases their surface area from 14.8 cm(2)
      g(-1) (LaMOFs) to 26.6 cm(2) g(-1) (LaMOF-GO3), whereas at the same time, the
      crystalline structure of La(BTC)(H2O)6 is maintained. As a novel solid-phase
      adsorbent the LaMOF-GO composite exhibits outstanding adsorption properties for
      proteins. The strong hydrophobic interaction, especially pi-pi interaction
      between protein and the composite, is the main driving force for protein
      adsorption. In particular, highly selective isolation of hemoglobin (Hb) is
      achieved by using LaMOF-GO3 composite as sorbent in 4 mM B-R buffer containing
      0.05 mol L(-1) NaCl at pH 8. The retained Hb could be effectively recovered with
      a 1 mM B-R buffer at pH 10, giving rise to a recovery of 63%. The practical
      applicability of the LaMOF-GO3 composite is demonstrated by the selective
      adsorption of Hb from human whole blood, and SDS-PAGE assays indicate that Hb
      could be selectively isolated with high purity from biological samples of complex
      matrixes. 

PMID- 24946900
TI  - Face to face activation of a phenylselenium borane with alpha,beta-unsaturated
      carbonyl substrates: facile synthesis of C-Se bonds.
AB  - Activated olefins directly react with a phenylselenium borane, at room
      temperature, without any metal or organocatalytic assistance. Up to 10 examples
      of beta-(phenylseleno) substituted ketones and aldehydes have been prepared and
      theoretical evidence for the mechanism opens up non-existing pathways to create C
      heteroatom bonds as a general tool. 

PMID- 24946902
TI  - Mechanistic insights into hydride transfer for catalytic hydrogenation of CO(2)
      with cobalt complexes.
AB  - The catalytic hydrogenation of CO2 to formate by Co(dmpe)2H can proceed via
      direct hydride transfer or via CO2 coordination to Co followed by reductive
      elimination of formate. The different nature of the rate-determining step in the
      two mechanisms may provide new insights into designing catalysts with improved
      performance. 

PMID- 24946903
TI  - A single element in the 3'UTR of the apical sodium-dependent bile acid
      transporter controls both stabilization and destabilization of mRNA.
AB  - mRNA stability appears to play a key role in the ontogenic regulation of the
      apical sodium-dependent bile acid transporter (ASBT). The RNA-binding proteins Hu
      antigen R (HuR) and tristetraprolin (TTP) stabilize and destabilize ASBT mRNA,
      respectively. Potential HuR-binding sites were assessed by sequence analysis in
      the context of prior in vitro functional analyses of the rat ASBT 3'UTR. Wild
      type and mutant-binding sites were investigated by gel-shift analysis using IEC-6
      cell extracts. The functional consequences of binding site mutations were
      assessed using two different hybrid reporter constructs linking the 3'UTR element
      to either a luciferase or a beta-globin coding mRNA sequence. A specific
      metastasis-associated gene 1 (MTA1) cis-element was identified in the ASBT 3'UTR
      that became associated with proteins in IEC-6 cell extracts and could be
      supershifted by anti-HuR or anti-TTP antibodies. Mutation of this cis-element
      abrogated the gel shift of IEC-6 proteins. Furthermore, hybrid constructs
      containing a mutant MTA1 element had reduced responses to modulation of HuR or
      TTP. For the first time, we have identified a single specific sequence element in
      the 3'UTR of the rat ASBT mRNA that mediates counter-regulatory changes in mRNA
      abundance in response to both HuR and TTP. 

PMID- 24946905
TI  - Effect of family background on the educational gradient in lifetime fertility of
      Finnish women born 1940-50.
AB  - An inverse association between education and fertility in women has been found in
      many societies but the causes of this association remain inadequately understood.
      We investigated whether observed and unobserved family-background characteristics
      explained educational differences in lifetime fertility among 35,212 Finnish
      women born in 1940-50. Poisson and logistic regression models, adjusted for
      measured socio-demographic family-background characteristics and for unobserved
      family characteristics shared by siblings, were used to analyse the relationship
      between education and the number of children, having any children, and fertility
      beyond the first child. The woman's education and the socio-economic position of
      the family were negatively associated with fertility. Observed family
      characteristics moderately (3-28 per cent) explained the association between
      education and fertility, and results from models including unobserved
      characteristics supported this interpretation. The remaining association may
      represent a causal relationship between education and fertility or joint
      preferences that form independently of our measures of background. 

PMID- 24946906
TI  - Hybrid architecture for encoded measurement-based quantum computation.
AB  - We present a hybrid scheme for quantum computation that combines the modular
      structure of elementary building blocks used in the circuit model with the
      advantages of a measurement-based approach to quantum computation. We show how to
      construct optimal resource states of minimal size to implement elementary
      building blocks for encoded quantum computation in a measurement-based way,
      including states for error correction and encoded gates. The performance of the
      scheme is determined by the quality of the resource states, where within the
      considered error model a threshold of the order of 10% local noise per particle
      for fault-tolerant quantum computation and quantum communication. 

PMID- 24946904
TI  - Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar
      morphogenesis and neural maturation.
AB  - Chromatin compaction mediates progenitor to post-mitotic cell transitions and
      modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h
      and Snf2l are ATP-dependent chromatin remodelling proteins that assemble,
      reposition and space nucleosomes, and are robustly expressed in the brain. Here
      we show that mice conditionally inactivated for Snf2h in neural progenitors have
      reduced levels of histone H1 and H2A variants that compromise chromatin fluidity
      and transcriptional programs within the developing cerebellum. Disorganized
      chromatin limits Purkinje and granule neuron progenitor expansion, resulting in
      abnormal post-natal foliation, while deregulated transcriptional programs
      contribute to altered neural maturation, motor dysfunction and death. However,
      mice survive to young adulthood, in part from Snf2l compensation that restores
      Engrailed-1 expression. Similarly, Purkinje-specific Snf2h ablation affects
      chromatin ultrastructure and dendritic arborization, but alters cognitive skills
      rather than motor control. Our studies reveal that Snf2h controls chromatin
      organization and histone H1 dynamics for the establishment of gene expression
      programs underlying cerebellar morphogenesis and neural maturation. 

PMID- 24946907
TI  - Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain
      unaffected by energy deprivation and display no day-night variation.
AB  - OBJECTIVE: To study the day-night variation of omentin-1 levels and assess
      whether leptin and/or short- and long-term energy deprivation alter circulating
      omentin-1 levels via cytokines. DESIGN AND METHODS: Omentin-1 levels were
      measured hourly in serum samples from six healthy men to evaluate for day-night
      variation. To study effects of acute energy deprivation and of leptin
      administration, eight healthy subjects were studied in the fasting state for 72 h
      with administration of either placebo or metreleptin (recombinant human leptin)
      in physiologic replacement doses. We evaluated the effect of leptin in
      pharmacologic doses on serum omentin-1 and cytokine levels, as well as on omentin
      1 levels in ex vivo omental adipose tissue, in 15 healthy volunteers. To study
      the effect of chronic energy deprivation and weight loss on omentin-1 levels, we
      followed 18 obese subjects for 12 months who underwent bariatric surgery.
      RESULTS: There is no day-night variation in omentin-1 levels. Short-term and
      chronic energy deprivation, as well as ex vivo leptin administration and
      physiologic replacement doses of leptin, do not alter omentin-1 levels;
      pharmacologic doses of metreleptin reduce omentin-1 levels, whereas levels of
      tumor necrosis factor-alpha receptor II and interleukin-6 tend to increase.
      CONCLUSIONS: Omentin-1 levels are reduced by pharmacologic doses of metreleptin
      independent of effects on cytokine levels.

PMID- 24946908
TI  - Influence of APOE-2 genotype on the relation between adiposity and plasma lipid
      levels in patients with vascular disease.
AB  - BACKGROUND: Apolipoprotein E (APOE) genotypes are associated with different
      plasma lipid levels. People with the APO E2 genotype can develop a disorder
      called dysbetalipoproteinemia (DBL). A possible predisposing factor for DBL is
      adiposity. We evaluated whether and to what extent the APOE genotype modifies the
      relation between adiposity and lipids in patients with manifest arterial disease
      and we looked at possible determinants of DBL in E2 homo- and heterozygote
      patients. METHODS: This prospective cohort study was performed in 5450 patients
      with manifest arterial disease from the Secondary Manifestations of ARTerial
      disease (SMART) study. The APOE genotype was measured in all patients and
      revealed 58 E2 homozygotes, 663 E2 heterozygotes, 3181 E3 homozygotes and 1548 E4
      carriers. The main dependent variable was non-high-density lipoprotein
      cholesterol (non-HDL-c). The relation between adiposity (including body mass
      index (BMI), waist circumference (waist), visceral adipose tissue (VAT) and
      metabolic syndrome (MetS)) and lipids was evaluated with linear regression
      analyses. Determinants of DBL were evaluated using logistic regression. RESULTS:
      There was significant effect modification by the APOE genotype on the relation
      between non-HDL-c and BMI, waist, VAT and MetS. There was an association between
      BMI and non-HDL-c in E2 homozygotes (beta 0.173, 95% confidence interval (CI)
      0.031-0.314, P=0.018) and E4 carriers (beta 0.033, 95% CI 0.020-0.046, P<0.001).
      In all genotypes, there was an effect of waist, VAT and MetS on non-HDL-c, but
      these effects were most distinct in E2 homozygotes (waist beta 0.063, 95% CI
      0.015-0.110, P=0.011; VAT beta 0.580, 95% CI 0.270-0.889, P=0.001; MetS beta
      1.760, 95% CI 0.668-2.852, P=0.002). Determinants of DBL in E2 homo- and
      heterozygotes were VAT and MetS. CONCLUSION: The APOE genotype modifies the
      relation between adiposity and plasma lipid levels in patients with vascular
      disease. The relation between adiposity and lipids is present in all patients,
      but it is most distinct in E2 homozygote patients. Abdominal fat and MetS are
      determinants of DBL.

PMID- 24946909
TI  - The clean plate club: about 92% of self-served food is eaten.
AB  - Many eating studies in psychology, consumer behavior and marketing journals are
      dismissed, because they focus on how much one serves and not how much is eaten.
      We develop a means of estimating the percentage of self-served food that is
      consumed under various conditions. An aggregate analysis was conducted of studies
      where participants served themselves food and where actual intake was measured.
      Analyses explored what percentage of food was consumed depending on population,
      food and situational cues and generally showed that adults consistently consume
      the vast majority (91.7%) of what they serve themselves. This was higher for
      meals (92.8%) than for snacks (76.1%) and higher when a person was not distracted
      (97.1%) than when he or she was distracted (88.8%). The percentage eaten did not
      vary between lab (90.7%) and field settings (91.9%). Because many eating behavior
      studies outside of nutrition measure food selection, but not intake, the
      aggregate estimates presented in this research can enable obesity, nutrition and
      public health researchers to extrapolate how much may have been eaten in such
      studies. Doing so will extend their relevance to better understanding eating
      behavior and better developing solutions to overeating. 

PMID- 24946911
TI  - Lotus leaf-like dual-scale silver film applied as a superhydrophobic and self
      cleaning substrate.
AB  - Lotus leaf-like and petal-like substrates were fabricated by chemical deposition,
      which have quite different superhydrophobic properties. Excellent, non-sticky,
      self-cleaning and durable properties were obtained based on the lotus leaf-like
      substrate. 

PMID- 24946910
TI  - Screen time, adiposity and cardiometabolic markers: mediation by physical
      activity, not snacking, among 11-year-old children.
AB  - BACKGROUND: There is evidence for a relation of TV viewing with adiposity and
      increased cardiometabolic risk factors in children and adolescents. It is unclear
      to what extent this relation is mediated by snacking and lack of physical
      activity. We determined whether associations of screen time with adiposity and
      cardiometabolic markers were mediated by these behaviours. METHODS: Children from
      a population-representative Dutch birth cohort (n=1447) reported screen time and
      other lifestyle factors by a questionnaire around the age of 11 years (range 10
      14) and had anthropometry and cardiometabolic markers measured around the age of
      12 years (range 12-14). Adjusted associations of screen time with snacking,
      physical activity, adiposity and cardiometabolic markers (total-to-high-density
      lipoprotein cholesterol (TC/HDLC) ratio, blood pressure, glycated haemoglobin)
      were assessed by using formal mediation analysis. We tested the hypothesized
      paths by structural equation modeling, which allows quantification of the
      indirect effects associated with potential mediators. RESULTS: Children with ?20
      h screen time per week consumed more snacks (1.9 vs 1.3 portions per day) and
      were less physically active (4.3 vs 4.8 days per week) than children with maximum
      6 h screen time. Screen time was directly associated with higher adiposity
      (standardized beta=0.10-0.12 depending on the outcome, P<0.001), and indirectly
      through less physical activity. The association of screen time with TC/HDLC ratio
      was almost completely mediated by adiposity (beta=0.39, P<0.0001), and to a minor
      extent by physical activity (beta=-0.06, P=0.02). There was no direct association
      of screen time with TC/HDLC ratio. CONCLUSIONS: The adverse association of screen
      time with adiposity was partly mediated by physical activity, but not by
      snacking. The association of screen time with TC/HDLC ratio was almost completely
      mediated by adiposity. Our results may suggest that future efforts in society and
      public health should be directed to replace screen time with physical activity
      for reducing children's adiposity and cardiometabolic risk.

PMID- 24946913
TI  - Bioanalysis for the development of respiratory drugs: what are the challenges?

PMID- 24946912
TI  - Exploring the association between maternal mood and self-reports of sleep during
      the perinatal period.
AB  - OBJECTIVE: To explore the psychological mechanisms involved in the close
      association between maternal mood and self-reports of sleep quality during the
      perinatal period using appraisal theory of emotions. DESIGN: Repeated measures.
      SETTING: Antenatal clinics of a health center associated with the Northern
      Hospital in Melbourne, Australia. PARTICIPANTS: 122 pregnant women in their third
      trimester of gestation. METHODS: Participants completed the Pittsburgh Sleep
      Quality Index (PSQI), the Edinburgh Postnatal Depression Scale, and an appraisal
      questionnaire during the third trimester of gestation, within 7 to 10 days after
      childbirth, and at 10 to 12 weeks postpartum. Correlational and regression
      analyses were used to explore the associations between sleep reports and
      appraisals. RESULTS: Self-reports of poor sleep quality, impaired daytime
      dysfunction due to poor sleep, and the global PSQI score were associated with a
      low perceived ability to cope practically and emotionally with motherhood-related
      issues as well as with negative expectations about the future. CONCLUSIONS:
      Appraisal dimensions associated with self-reports of poor sleep quality are
      similar to those related to maternal distress identified by previous research.
      This finding contributes to a better understanding of the association between
      self-reports of sleep and maternal mood. Practical implications are discussed.

PMID- 24946914
TI  - What are the advantages of RP-HPLC methods for the detection of drugs in plasma?

PMID- 24946916
TI  - Conference report: moving forward together: "we are making progress".
AB  - The 6th European Bioanalysis Forum Open Meeting 20-22 November 2013, Hesperia
      Tower Hotel, Barcelona, Spain At the 6th European Bioanalysis Forum Open Meeting,
      held from 20-22 November 2013 in Hesperia Tower Hotel, Barcelona, Spain,
      bioanalytical experts from pharmaceutical industry, academia, contract
      laboratories and regulatory bodies discussed current topics of interest in
      bioanalysis. 450 delegates from more than 170 institutes and companies
      participated in 75 open and stimulating presentations regarding the new US FDA
      Guidance for industry, technology updates, including liquid chromatography-mass
      spectrometry of proteins and antibody-drug conjugates, dried blood spots,
      sampling and extraction and regulatory aspects of, for example, flow cytometry,
      parallelism, and interferences in ligand-binding assays. This article aims to
      provide an overview of the highlights discussed at the meeting. 

PMID- 24946917
TI  - Ask the experts: chromatographic baselines.
AB  - Bioanalysis invited a selection of leading researchers to express their views on
      chromatographic baseline assignment in the bioanalytical laboratory. The topics
      discussed include the challenges presented with ensuring automated baseline
      assignment is correct, when reintegration is necessary, regulation and
      consistency in terminology. Their enlightening responses provide a valuable
      insight into developing an industry consensus towards reintegration. An
      accompanying commentary article in this issue, authored by Howard Hill and
      colleagues (Huntingdon Life Sciences), provides background to this much debated
      topic. 

PMID- 24946918
TI  - Manual chromatographic baseline integration: is it needed, if so when should it
      be used?

PMID- 24946919
TI  - Miniaturization of multiplexed planar recombinant antibody arrays for serum
      protein profiling.
AB  - BACKGROUND: Antibody-based microarrays are a developing tool for high-throughput
      proteomics in health and disease. However, in order to enable global proteome
      profiling, novel miniaturized high-density antibody array formats must be
      developed. RESULTS: In this proof-of-concept study, we have designed a
      miniaturized planar recombinant (single-chain Fragment variable). antibody array
      technology platform for multiplexed profiling of non-fractionated, directly
      labelled serum samples. The size of the individual spot features was reduced 225
      times (78.5 MUm(2)/spot) and the array density was increased 19-times (38,000
      spots/cm(2)). These miniaturized, multiplexed arrays were produced, using a
      desktop nanofabrication system based on dip-pen nanolithography technology, and
      interfaced with a high-resolution fluorescent-based scanner. The reproducibility,
      sensitivity, specificity, and applicability of the set-up were demonstrated by
      profiling a set of well-characterized serum samples. CONCLUSION: The designed
      antibody array platform opens up new possibilities for large-scale, multiplex
      profiling of crude proteomes in a miniaturized fashion.

PMID- 24946920
TI  - Metabolism of RCS-8, a synthetic cannabinoid with cyclohexyl structure, in human
      hepatocytes by high-resolution MS.
AB  - BACKGROUND: Since 2008, synthetic cannabinoids are major new designer drugs of
      abuse. They are extensively metabolized and excreted in urine, but limited human
      metabolism data are available. As there are no reports on the metabolism of RCS
      8, a scheduled phenylacetylindole synthetic cannabinoid with an N-cyclohexylethyl
      moiety, we investigated metabolism of this new designer drug by human hepatocytes
      and high resolution MS. METHODS: After human hepatocyte incubation with RCS-8,
      samples were analyzed on a TripleTOF 5600+ mass spectrometer with time-of-flight
      survey scan and information-dependent acquisition triggered product ion scans.
      Data mining of the accurate mass full scan and product ion spectra employed
      different data processing algorithms. RESULTS & CONCLUSION: More than 20 RCS-8
      metabolites were identified, products of oxidation, demethylation, and
      glucuronidation. Major metabolites and targets for analytical methods were
      hydroxyphenyl RCS-8 glucuronide, a variety of hydroxycyclohexyl-hydroxyphenyl RCS
      8 glucuronides, hydroxyphenyl RCS-8, as well as the demethyl-hydroxycyclohexyl
      RCS-8 glucuronide.

PMID- 24946921
TI  - LC-MS/MS quantification of next-generation biotherapeutics: a case study for an
      IgE binding Nanobody in cynomolgus monkey plasma.
AB  - BACKGROUND: Nanobodies((r)) are therapeutic proteins derived from the smallest
      functional fragments of heavy chain-only antibodies. The development and
      validation of an LC-MS/MS-based method for the quantification of an IgE binding
      Nanobody in cynomolgus monkey plasma is presented. RESULTS: Nanobody
      quantification was performed making use of a proteotypic tryptic peptide
      chromatographically enriched prior to LC-MS/MS analysis. The validated LLOQ at 36
      ng/ml was measured with an intra- and inter-assay precision and accuracy <20%.
      The required sensitivity could be obtained based on the selectivity of 2D LC
      combined with MS/MS. No analyte specific tools for affinity purification were
      used. Plasma samples originating from a PK/PD study were analyzed and compared
      with the results obtained with a traditional ligand-binding assay. Excellent
      correlations between the two techniques were obtained, and similar PK parameters
      were estimated. CONCLUSION: A 2D LC-MS/MS method was successfully developed and
      validated for the quantification of a next generation biotherapeutic.

PMID- 24946922
TI  - A lipemia-independent NanoDrop((r))-based score to identify hemolysis in plasma
      and serum samples.
AB  - BACKGROUND: The identification and management of hemolyzed samples are crucial
      issues in the development of new blood-based biomarkers. RESULTS: Using
      experiments of controlled hemolysis and lipemia and two plasma series from cancer
      patients, we developed and validated a lipemia-independent hemolysis score (HS).
      HS resulted strictly associated with the amount of lysed erythrocytes and with
      serum index measurement (reference method), highly reproducible, and able to
      identify as hemolyzed plasma/serum samples containing >=6.1 mg/dl of free
      hemoglobin. CONCLUSION: We developed a simple, robust, sensitive, cost-effective,
      spectrophotometrically-based system to identify hemolyzed plasma/serum specimens.
      The procedure requires only 2 MUl of sample, thus representing a useful tool for
      research studies and an essential pre-analytical quality control for an optimal
      biobanking of liquid biopsies.

PMID- 24946923
TI  - In vivo and ex vivo SPME: a low invasive sampling and sample preparation tool in
      clinical bioanalysis.
AB  - Solid phase microextraction (SPME) is well-established technology in bioanalysis.
      Current review discusses the features of SPME, which determine the non- or low
      invasiveness of the method in biomedical analysis. In the first section we
      analyze the factors, which have significant influence on the SPME sampling device
      performance in the view of sampling safety and efficiency. In the later sections
      applicability of various SPME approaches for analysis of easily accessible
      samples routinely used for analysis (e.g., urine, blood) as well as limited
      availability samples (tissues) is discussed. Moreover, the examples of sampling
      alternative matrices such as hair, saliva, sweat or breath are presented. The
      advantages and limitation of the technology in the view of future development of
      SPME are also reviewed. 

PMID- 24946924
TI  - In situ drug and metabolite analysis [corrected] in biological and clinical
      research by MALDI MS imaging.
AB  - In recent years the analysis in mass spectrometry (MS) [corrected] imaging has
      been expanded to detect a wide variety of low molecular weight compounds (LMWC),
      including exogenous and endogenous compounds. The high sensitivity and
      selectivity of MS imaging combined with visualization of molecular spatial
      distribution in tissues, makes it a valuable [corrected] platform in targeted
      drug and untargeted metabolomic analysis [corrected] in biological and clinical
      research. Here, we review the current and potential applications of MALDI MS
      imaging in these areas. The aim of advancing MALDI MS imaging in the field of
      LMWC is to support clinical applications by understanding drug and drug
      metabolite distribution, investigating toxicity and discovering [corrected] new
      biomarkers.

PMID- 24946925
TI  - Multi-target screening of biological samples using LC-MS/MS: focus on
      chromatographic innovations.
AB  - Multi-target screening of biological fluids is a key tool in clinical and
      forensic toxicology. A complete toxicological analysis encompasses the sample
      preparation, the chromatographic separation and the detection. The present review
      briefly covers the new trends in sample preparation and detection and mainly
      focuses on the chromatographic stage, since a lot of technical improvements have
      been proposed over the last years. Among them, columns packed with sub-2 MUm
      fully porous particles and sub-3 MUm core-shell particles allow for significant
      improvements of resolution and higher throughput. Even if reversed-phase LC
      remains the most widely used chromatographic mode for toxicological screening,
      hydrophilic interaction chromatography and supercritical fluid chromatography
      appear as promising alternatives for attaining orthogonal selectivity, retention
      of polar compounds, and enhanced MS sensitivity. 

PMID- 24946926
TI  - A recombinant RNA bacteriophage system to identify functionally important
      nucleotides in a self-cleaving ribozyme.
AB  - BACKGROUND: RNA bacteriophages like Qbeta and MS2 are well known for their high
      mutation rate, short infection cycle and strong selection against foreign
      inserts. The hammerhead ribozyme (HHRz) is a small self-cleaving RNA molecule
      whose active residues have previously been identified by mutational analysis of
      each individual base. Here the functionally important bases of HHRz were
      determined in a single screening experiment by inserting the HHRz into the genome
      of MS2. FINDINGS: The minimal HHRz of satellite Tobacco ringspot virus was cloned
      into the genome of RNA bacteriophage MS2. Sequence analysis of the surviving
      phages revealed that the majority had acquired single base-substitutions that
      apparently inactivated the HHRz. The positions of these substitutions exactly
      matched that of the previously determined core residues of the HHRz. CONCLUSIONS:
      Natural selection against a ribozyme in the genome of MS2 can be used to quickly
      identify nucleotides required for self-cleavage.

PMID- 24946927
TI  - Spatial correlation analysis of cascading failures: congestions and blackouts.
AB  - Cascading failures have become major threats to network robustness due to their
      potential catastrophic consequences, where local perturbations can induce global
      propagation of failures. Unlike failures spreading via direct contacts due to
      structural interdependencies, overload failures usually propagate through
      collective interactions among system components. Despite the critical need in
      developing protection or mitigation strategies in networks such as power grids
      and transportation, the propagation behavior of cascading failures is essentially
      unknown. Here we find by analyzing our collected data that jams in city traffic
      and faults in power grid are spatially long-range correlated with correlations
      decaying slowly with distance. Moreover, we find in the daily traffic, that the
      correlation length increases dramatically and reaches maximum, when morning or
      evening rush hour is approaching. Our study can impact all efforts towards
      improving actively system resilience ranging from evaluation of design schemes,
      development of protection strategies to implementation of mitigation programs. 

PMID- 24946928
TI  - How important is peri-operative hypertension?

PMID- 24946930
TI  - Survivin suppression through STAT3/beta-catenin is essential  for resveratrol
      induced melanoma apoptosis.
AB  - Although many chemotherapies have been developed for melanomas, successful
      therapy would be aided by the identification of intrinsic mechanisms that are
      crucial for melanoma survival. Here, we used resveratrol, a phytoalexin, as an
      anti-melanoma reagent. Applying resveratrol to various human and murine melanoma
      cell lines, we show that survivin is essential for melanoma survival in vitro and
      in vivo and is targeted by resveratrol. Furthermore, we identify the down
      regulation of survivin transcription by resveratrol through the suppression of
      beta-catenin and STAT3. In addition, over expression of survivin protects
      melanoma cells from resveratrol-induced apoptosis. Collectively, these studies
      establish that targeting survivin could provide an opportunity to treat melanoma
      patients.

PMID- 24946931
TI  - The prospect of molecular therapy for Angelman syndrome and other monogenic
      neurologic disorders.
AB  - BACKGROUND: Angelman syndrome is a monogenic neurologic disorder that affects 1
      in 15,000 children, and is characterized by ataxia, intellectual disability,
      speech impairment, sleep disorders, and seizures. The disorder is caused by loss
      of central nervous system expression of UBE3A, a gene encoding a ubiquitin
      ligase. Current treatments focus on the management of symptoms, as there have not
      been therapies to treat the underlying molecular cause of the disease. However,
      this outlook is evolving with advances in molecular therapies, including
      artificial transcription factors a class of engineered DNA-binding proteins that
      have the potential to target a specific site in the genome. RESULTS: Here we
      review the recent progress and prospect of targeted gene expression therapies.
      Three main issues that must be addressed to advance toward human clinical trials
      are specificity, toxicity, and delivery. CONCLUSIONS: Artificial transcription
      factors have the potential to address these concerns on a level that meets and in
      some cases exceeds current small molecule therapies. We examine the possibilities
      of such approaches in the context of Angelman syndrome, as a template for other
      single-gene, neurologic disorders.

PMID- 24946933
TI  - NOX4 promotes non-small cell lung cancer cell proliferation and metastasis
      through positive feedback regulation of PI3K/Akt signaling.
AB  - NADPH oxidase 4 (NOX4) is deregulated in various cancers and involved in cancer
      proliferation and metastasis. However, what the role of NOX4 plays during
      malignant progression of non-small cell lung cancer (NSCLC) remains unknown. Our
      results show that NOX4 was upregulated in NSCLC cell lines and samples from
      patients, compared with controls; NOX4 protein levels were closely correlated
      with clinical disease stage and survival time. Overexpression of NOX4 in A549 and
      H460 NSCLC cells enhanced cell proliferation and invasion in vitro, and produced
      larger tumors, shorter survival time, and more lung metastasis in nude mice than
      control cells. On the contrary, NOX4 depletion inhibited NSCLC cell
      aggressiveness. Inhibition of PI3K/Akt pathway could sufficiently block the
      cellular effects of NOX4 overexpression in NSCLC cells both in vitro and in vivo.
      Specifically, we demonstrated that PI3K/Akt pathway also positively regulated
      NOX4 expression via NF-kappaB-mediated manner. Therefore, there existed a mutual
      positive regulation between NOX4 and PI3K/Akt signaling in NSCLC cells, and NOX4
      was confirmed to functionally interplay with PI3K/Akt signaling to promote NSCLC
      cell proliferation and invasion. In conclusion, the positive feedback loop
      between NOX4 and PI3K/Akt signaling contributes to NSCLC progression. 

PMID- 24946932
TI  - Hepatic progenitor cells in canine and feline medicine: potential for
      regenerative strategies.
AB  - New curative therapies for severe liver disease are urgently needed in both the
      human and veterinary clinic. It is important to find new treatment modalities
      which aim to compensate for the loss of parenchymal tissue and to repopulate the
      liver with healthy hepatocytes. A prime focus in regenerative medicine of the
      liver is the use of adult liver stem cells, or hepatic progenitor cells (HPCs),
      for functional recovery of liver disease. This review describes recent
      developments in HPC research in dog and cat and compares these findings to
      experimental rodent studies and human pathology. Specifically, the role of HPCs
      in liver regeneration, key components of the HPC niche, and HPC activation in
      specific types of canine and feline liver disease will be reviewed. Finally, the
      potential applications of HPCs in regenerative medicine of the liver are
      discussed and a potential role is suggested for dogs as first target species for
      HPC-based trials. 

PMID- 24946934
TI  - Chitosan hydrogel as siRNA vector for prolonged gene silencing.
AB  - BACKGROUND: The periodontitis is one of the most prevalent diseases with alveolar
      resorption in adult people and is the main cause of the tooth loss. To
      investigate the possibility for protecting the loss of alveolar bone in
      periodontal diseases, a RNAi-based therapeutic strategy is applied for silencing
      RANK signaling using thermosensitive chitosan hydrogel as siRNA reservoir and
      vector. RESULTS: The thermosensitive chitosan hydrogel was formed from solution
      (PH = 7.2, at 4 degrees C) at 37 degrees C within 8 minutes. The degradation
      rates of hydrogel were ~50% and 5% (W remaining/W beginning) in the presence and
      absence of lysozyme, respectively, over a period of 20 days. The concurrent
      cumulative in vitro release of Cy3-labeled siRNA from the hydrogel was 50% and
      17% over 14 days, with or without lysozyme digestion, respectively. High cell
      viability (>88%) was maintained for cells treated with hydrogel loaded with RANK
      specific siRNA and RANK knockdown was prolonged for up to 9 days when cells were
      incubated with siRNA/hydrogel complex. In vivo release of siRNA was investigated
      in a subcutaneous delivery setup in mice. The fluorescent signal from siRNA
      within hydrogel was remained for up to 14 days compared to less than one day for
      siRNA alone. CONCLUSIONS: Chitosan hydrogel can potentially serve as a suitable
      reservoir and vector for local sustained delivery of siRNA in potential therapy.

PMID- 24946935
TI  - Providing nutrition education to recently resettled refugees: piloting a
      collaborative model and evaluation methods.
AB  - Resettled refugees experience high levels of food insecurity because of low
      English proficiency, limited job skills, and lack of understanding of the United
      States food system. This study evaluated integrating Supplemental Nutrition
      Assistance Program Education (SNAP-Ed) into English as Second Language (ESL)
      classes taught at a worksite- training program for recently resettled refugees
      and the feasibility of using food purchase receipts. A convenience sample of
      resettled refugees participated in SNAP-Ed one hour for 12 weeks during ESL
      classes. Food purchase receipts were collected for purchases one week prior to,
      first three weeks, last three weeks, and one week after classes. Participants
      were from 17 countries and 50% completed 12 lessons. Fifty-nine participants
      turned in receipts and 93% used SNAP funds. By integrating SNAP-Ed into ESL
      classes at a worksite-training center a hard-to-reach eligible population was
      reached. Further validation is needed to use food purchase receipts.

PMID- 24946936
TI  - Effect of Influenza Vaccination on Acute Respiratory Symptoms in Malaysian Hajj
      Pilgrims.
AB  - Respiratory illness were a major problem and caused high hospital admission
      during hajj seasons. One of the contributing cause to this illness is infection.
      Various measures had been implemented to reduce respiratory infections. The aim
      on the study is to determine the effect of influenza vaccination against acute
      respiratory illness among Malaysian Hajj pilgrims. This is an observational
      cohort study. Influenza vaccination was given to pilgrims at least 2 weeks prior
      to departure. The occurrence of symptoms for respiratory illness such as cough,
      fever, sore throat and runny nose was monitored daily for 6 weeks during
      pilgrimage using a health diary. A total of 65 vaccinated hajj pilgrims and 41
      controls were analyzed. There was no significant difference in pattern of
      occurrence of symptoms of respiratory illness by duration of pilgrimage as well
      as the number of symptoms between both groups. Hajj pilgrims have frequent
      respiratory symptoms. We were unable to document benefit from influenza
      vaccination, but our study was limited by a small sample size and lack of
      laboratory testing for influenza. 

PMID- 24946938
TI  - Jejunal torsion around the right ureter presenting as postoperative bowel
      obstruction: a case report.
AB  - INTRODUCTION: Since abdominal radical hysterectomy was first described by Clark
      and Reis in 1895, it has been commonly used in the primary surgical treatment of
      carcinoma of the cervix. We report the case of a 45-year-old woman who was
      diagnosed with a small bowel obstruction due to jejunal torsion to her right
      ureter mimicking postoperative adhesion ileus. CASE PRESENTATION: A 45-year-old
      Turkish woman was admitted to our emergency department with complaints of
      abdominal pain, constipation, nausea and vomiting. She had undergone an abdominal
      radical hysterectomy for cervical carcinoma three years earlier. Computed
      tomography scans revealed intestinal dilatation, a large amount of free fluid in
      the abdominal cavity and an area suspicious for jejunal perforation. Because of
      these radiological findings suggestive of obstruction and bowel ischemia, our
      patient underwent emergency surgery. Operative findings that showed a jejunal
      segment was turned around her right ureter so that it was mimicking a fibrous
      band. CONCLUSIONS: In this current case, we present the first determined
      complication of radical hysterectomy. According to our case report, surgical
      oncologists should be aware of this complication and review the surgical
      technique. It is considered that readaptation of the dorsolateral peritoneal
      layer after extended pelvic lymph node dissection resulted in fewer
      complications.

PMID- 24946937
TI  - Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and
      investigation of the antitumor effects of pazopanib on Hewga-CCS.
AB  - BACKGROUND: Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive,
      soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma
      is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing
      sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a
      chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga
      CCS and developed an orthotopic tumor xenograft model to enable comprehensive
      bench-side investigation for intensive basic and preclinical research in CCS with
      a paucity of experimental cell lines. METHODS: Hewga-CCS was derived from skin
      metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and
      chimeric transcript were analyzed. Xenografts were established and characterized
      by morphology and immunohistochemical reactivity. Subsequently, the antitumor
      effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase
      inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga
      CCS were assessed in vitro and in vivo. RESULTS: Hewga-CCS harbored the type 2
      EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and
      expressed S-100 protein and antigens associated with melanin synthesis (Melan-A,
      HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A
      phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not
      of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted
      antitumor effects through the inhibition of HGF/c-MET signaling. CONCLUSIONS: CCS
      is a rare, devastating disease, and our established CCS cell line and xenograft
      model may be a useful tool for further in-depth investigation and understanding
      of the drug-sensitivity mechanism.

PMID- 24946939
TI  - A wireless power transmission system for implantable devices in freely moving
      rodents.
AB  - Reliable wireless power delivery for implantable devices in animals is highly
      desired for safe and effective experimental use. Batteries require frequent
      replacement; wired connections are inconvenient and unsafe, and short-distance
      inductive coupling requires the attachment of an exterior transmitter to the
      animal's body. In this article, we propose a solution by which animals with
      implantable devices can move freely without attachments. Power is transmitted
      using coils attached to the animal's cage and is received by a receiver coil
      implanted in the animal. For a three-dimensionally uniform delivery of power, we
      designed a columnar dual-transmitter coil configuration. A resonator-based
      inductive link was adopted for efficient long-range power delivery, and we used a
      novel biocompatible liquid crystal polymer substrate as the implantable receiver
      device. Using this wireless power delivery system, we obtain an average power
      transfer efficiency of 15.2% (minimum efficiency of 10% and a standard deviation
      of 2.6) within a cage of 15*20*15 cm3.

PMID- 24946941
TI  - Guillain-Barre syndrome and encephalitis/encephalopathy associated with acute
      severe hepatitis E infection.

PMID- 24946940
TI  - Effects of analog P165 of amyloid precursor protein 5-mer peptide on learning,
      memory and brain insulin receptors in the rat model of cognitive decline.
AB  - We aim to study the therapeutic efficacy of analog P165 of amyloid precursor
      protein 5-mer peptide in streptozotocin (STZ)-induced cognitive decline model.
      Rats were divided into four groups: control, STZ, STZ+P165, and STZ+rosiglitazone
      (RSG). STZ model was established by intracerebroventricular injection of STZ.
      Three weeks following surgery, rats received daily gavage administration of
      distilled water (control and STZ groups), P165 (STZ+P165), or RSG (STZ+RSG) for
      four consecutive weeks. Learning and memory abilities were assessed with the
      Morris water maze test. Insulin-like growth factor-1 (IGF-1) was detected by
      ELISA. Expressions of insulin receptor-beta (IR-beta), insulin receptor substrate
      1 (IRS-1), serine/threonine kinase (Akt), and phosphorylation of CREB (p-CREB)
      were observed by immunohistochemistry. Both P165 and RSG significantly reduced
      the escape latency relative to the STZ group (P165, P < 0.05; RSG, P < 0.01). STZ
      model rats had reduced levels of IGF-1 relative to control, and this deficit was
      attenuated in the STZ+P165 group (P < 0.01). IR and IRS-1 were elevated in STZ
      rats, and these levels were restored to near control in the STZ+P165 and STZ+RSG
      groups (P < 0.01). Our findings demonstrate that P165 and RSG improved
      hippocampus-dependent spatial learning and memory in STZ rats by regulating the
      insulin signaling pathway.

PMID- 24946942
TI  - Intracranial facial nerve crush injury and facial motor nuclei cell loss in rats.
AB  - OBJECTIVES: The purpose of this study was to (1) assess the degree of motoneuron
      cell loss and (2) the combinatorial effects of electrical stimulation (ES) and
      testosterone propionate (TP) on cell survival following an intracranial facial
      nerve crush injury and (3) compare these results to distal injuries. STUDY
      DESIGN: Prospective, randomized, controlled animal study. METHODS: Sprague-Dawley
      rats were randomly divided into 3 groups: intracranial sham surgery or
      intracranial crush injury with or without ES and TP treatments. The intracranial
      sham group underwent exposure of the meatal segment of the right facial nerve.
      The intracranial crush groups underwent a crush of the meatal segment following
      exposure with or without ES and TP treatment immediately following the injury and
      followed for 8 weeks. Brain sections were thionin-stained, and facial motor
      nuclei (FMN) were counted using light microscopy. Results were compared to
      intratemporal and extracranial facial nerve crush injuries. RESULTS: Intracranial
      crush injury resulted in a significant decrease in cell survival (n = 6) of 65.6%
      as compared to the sham group (99.4%; n = 9). The treatments increased cell
      survival to 93.8% (n = 2). The cell loss in the intracranial facial nerve injury
      is more substantial than the intratemporal (85.8%; n = 7) and extracranial
      (103.3%; n = 4) injuries. CONCLUSIONS: Intracranial injury results in a more
      profound cell loss compared to the distal injuries. These data suggest a critical
      importance for the development of treatment modalities that can help improve cell
      survival following facial nerve injuries.

PMID- 24946943
TI  - QTL analysis of internode elongation in response to gibberellin in deepwater
      rice.
AB  - Gibberellin (GA) is a plant hormone that has important roles in numerous plant
      developmental phases. Rice plants known as deepwater rice respond to flooding by
      elongating their internodes to avoid anoxia. Previous studies reported that GA is
      essential for internode elongation in deepwater rice. Quantitative trait locus
      (QTL) analyses identified QTLs regulating internode elongation in response to
      deepwater conditions. However, the interaction between internode elongation and
      regulators of GA sensitivity in deepwater rice is unknown. In this study, we
      applied GA to recombinant inbred lines of T65 (non-deepwater rice) and Bhadua
      (deepwater rice), and performed a QTL analysis of internode elongation in
      response to GA. GA-induced internode elongation was detected only in deepwater
      rice. Our QTL analysis revealed two major QTLs on chromosomes 3 and 9 regulating
      total internode length, lowest elongated internode and number of elongated
      internodes. Furthermore, the QTL on chromosome 3 acted as an enhancer of other
      QTLs (e.g. the QTL on chromosome 12). Nearly isogenic lines of deepwater rice
      carrying the QTL regions from chromosomes 3 and 12 of the deepwater rice C9285
      showed internode elongation in response to GA. Thus, these QTLs may regulate GA
      responsiveness in deepwater rice. This study furthers our understanding of the
      mechanism of internode elongation in rice. 

PMID- 24946944
TI  - Are clinical practice guidelines for cataract and glaucoma trustworthy?

PMID- 24946945
TI  - Nasal continuous positive airway pressure therapy in a non-tertiary neonatal
      unit: reduced need for up-transfers.
AB  - OBJECTIVE: To evaluate the need for up-transfer after starting of nasal
      continuous positive airway pressure (n-CPAP) services in a Level II special
      newborn care unit (SNCU). METHODS: Five hundred fifty infants admitted to Level
      II SNCU, 252 infants during one year prior to introduction of n-CPAP
      (retrospective data from case records and electronic data base) and 298 infants
      during one year after introduction of n-CPAP services (prospective data in
      predefined case reporting form) were evaluated in this before and after
      intervention trial. The primary outcome was proportion of infants needing up
      transfers from Level II SNCU for any indication. RESULTS: Baseline demographic
      data like birth weight, gestation and other perinatal factors were similar
      between the two epochs. Among the infants admitted to Level II SNCU, up-transfer
      for any reason was significantly higher in the pre-CPAP epoch compared with CPAP
      epoch (n = 93, 36 % vs. n = 74, 24.8 %, p = 0.002, OR 0.56, 95 % CI 0.38 to
      0.83). However parent desired up-transfers were similar between the two epochs (n
      = 9, 3 % vs. n = 16, 5 %, p = 0.40). Introduction of n-CPAP treatment modality
      reduced up-transfers in subgroups of very low birth weight infants (VLBW) (n =
      20, 74 % vs. n = 15, 37 %, p = 0.003) and also in preterm infants (n = 50, 54 %
      vs. n = 34, 32 %, p = 0.002). CONCLUSIONS: Introduction of n-CPAP services in a
      non-tertiary care neonatal unit, significantly reduced the need for up-transfers,
      especially in VLBW and preterm infants.

PMID- 24946946
TI  - Conditioned avoidance responses survive contingency degradation in the garden
      slug, Lehmannia valentiana.
AB  - Joint presentations of a conditioned stimulus (CS) and an unconditioned stimulus
      (US) strengthen the contingency between them, whereas presentations of one
      stimulus without the other degrade this contingency. For example, the CS can be
      presented without the US either before conditioning (CS-no US and then CS-US;
      latent inhibition) or after conditioning (CS-US and then CS-no US; extinction).
      In vertebrate subjects and several invertebrate species, a time lapse usually
      results in a return of the conditioned response, or spontaneous recovery.
      However, in land mollusks, spontaneous recovery from extinction has only recently
      been reported, and response recovery after latent inhibition has not been
      reported. In two experiments, using conditioned aversion to a food odor as a
      measure of learning and memory retention, we observed contingency degradation via
      latent inhibition (Experiment 1) and extinction (Experiment 2) in the common
      garden slug, Lehmannia valentiana. In both situations, the contingency
      degradation procedure successfully attenuated conditioned responding, and
      delaying testing by several days resulted in recovery of the conditioned
      response. This suggests that the CS-US association survived the degradation
      manipulation and was retained over an interval of several days.

PMID- 24946947
TI  - Accuracy of MR in growth plate measurement.
AB  - PURPOSE: To analyze the accuracy of growth-plate thickness measurements detected
      on 1.5-T and 7-T MR images using histology sections as a standard of reference.
      MATERIALS AND METHODS: Four defrosted pig tibiae were 1.5-T MR scanned and one
      fresh tibia was 7-T MR scanned. The height of the growth plate was measured and
      compared to histology. RESULTS: Histology measurements showed a mean growth plate
      thickness of 467 MUm (SD = 82.2). The mean growth plate thickness measured in the
      7-T MR images was 465 MUm (SD = 62.2) and 1,325 MUm (SD = 183.5) on 1.5-T MR
      measurements. We found a better correspondence between the growth plate thickness
      measured on the 7-T MR and histology samples compared to 1.5 T. CONCLUSIONS: The
      growth plate can be identified and measured with high accuracy using 7-T MR. 1.5
      T MR can only describe some morphological characteristics.

PMID- 24946948
TI  - Identification of human single-chain antibodies with broad reactivity for
      noroviruses.
AB  - Norovirus infections are a common cause of gastroenteritis and new methods to
      rapidly diagnose norovirus infections are needed. The goal of this study was to
      identify antibodies that have broad reactivity of binding to various genogroups
      of norovirus. A human scFv phage display library was used to identify two
      antibodies, HJT-R3-A9 and HJT-R3-F7, which bind to both genogroups I and II
      norovirus virus-like particles (VLPs). Mapping experiments indicated that the HJT
      R3-A9 clone binds to the S-domain while the HJT-R3-F7 clone binds the P-domain of
      the VP1 capsid protein. In addition, a family of scFv antibodies was identified
      by elution of phage libraries from the GII.4 VLP target using a carbohydrate that
      serves as an attachment factor for norovirus on human cells. These antibodies
      were also found to recognize both GI and GII VLPs in enzyme-linked immunosorbent
      assay (ELISA) experiments. The HJT-R3-A9, HJT-R3-F7 and scFv antibodies
      identified with carbohydrate elution were shown to detect antigen from a clinical
      sample known to contain GII.4 norovirus but not a negative control sample.
      Finally, phages displaying the HJT-R3-A9 scFv can be used directly to detect both
      GI.1 and GII.4 norovirus from stool samples, which has the potential to simplify
      and reduce the cost of diagnostics based on antibody-based ELISA methods. 

PMID- 24946949
TI  - A variant pattern of calretinin immunohistochemistry on rectal suction-biopsies
      is fully specific of short-segment Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Calretinin immunohistochemistry is now widely used to
      diagnose Hirschsprung's disease (HD), since loss of calretinin expression within
      the mucosa and muscularis mucosae of rectal suction-biopsy is pathognomonic of
      HD. However, a stippled staining may be observed within hypertrophic nerves in
      the submucosae in some HD patients. The aim of the study was to test the
      hypothesis that such findings may announce the beginning of the transitional
      zone. METHODS: We retrieved 44 consecutive patients (10 girls and 34 boys; median
      age 6.5 days), diagnosed with aganglionosis on rectal suction biopsies, followed
      by surgery. According to calretinin immunohistochemistry performed on all
      paraffin-embedded rectal biopsies, we defined two HD groups: P- showing an
      absence of any staining within mucosa, muscularis mucosae and submucosa et P+
      showing an absence of staining within the mucosa and muscularis mucosae, but a
      positivity of some submucosal hypertrophic nerves. These data were correlated to
      the length of total pathological segment (aganglionic and transitional zones)
      obtained from the original surgery reports. RESULTS: 18/44 patients (40.9 %)
      belonged to the P+ group and 26/44 (59 %) patients were within the P- group. In
      the P+ group, the maximal length of the aganglionic zone was 9 cm [mean 4 (1-9)]
      and the total pathological zone never exceeded 14 cm [mean 8 (3.8-14)]. In the P-
      group, the maximal length of aganglionic zone was 55.5 cm [mean 11.3 (2.5; 55.5)]
      and the total pathological zone extended to 59.5 cm [mean 17.75 (4.5; 59.5)].
      Aganglionic segment was significantly shorter in the P+ group (p < 0.0001).
      CONCLUSION: Staining of some hypertrophic nerves in the submucosa in suction
      rectal biopsy of HD patients using calretinin immunohistochemistry is only
      encountered in short-segment aganglionosis with a pathological zone always
      restricted to rectal and sigmoid colon. This information could be crucial for the
      surgeons in the decision to choose a transanal procedure.

PMID- 24946950
TI  - Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer
      cells: enhancement of their invasive behavior partly dependant on alphav
      integrins.
AB  - At least one-third of patients with epithelial ovarian cancer (OC) present
      ascites at diagnosis and almost all have ascites at recurrence. The presence of
      ascites, which acts as a dynamic reservoir of active molecules and cellular
      components, correlates with the OC peritoneal metastasis and is associated with
      poor prognosis. Since epithelial-mesenchymal transition (EMT) is involved in
      different phases of OC progression, we have investigated the effect of the unique
      ascitic tumor microenvironment on the EMT status and the behavior of OC cells.
      The exposure of three OC cell lines to ascites leads to changes in cellular
      morphologies. Within ascites, OC cells harboring an initial intermediate
      epithelial phenotype are characterized by marked dislocation of epithelial
      markers (E-cadherin, ZO-1 staining) while OC cells initially harboring an
      intermediate mesenchymal phenotype strengthen their mesenchymal markers (N
      cadherin, vimentin). Ascites differentially triggers a dissemination phenotype
      related to the initial cell features by either allowing the proliferation and the
      formation of spheroids and the extension of colonies for cells that present an
      initial epithelial intermediate phenotype, or favoring the migration of cells
      with a mesenchymal intermediate phenotype. In an ascitic microenvironment, a
      redeployment of alphav integrins into cells was observed and the ascites-induced
      accentuation of the two different invasive phenotypes (i.e. spheroids formation
      or migration) was shown to involve alphav integrins. Thus, ascites induces a
      shift toward an unstable intermediate state of the epithelial-mesenchymal
      spectrum and confers a more aggressive cell behavior that takes on a different
      pathway based on the initial epithelial-mesenchymal cell features. 

PMID- 24946951
TI  - Metadherin expression and lung relapse in patients with colorectal carcinoma.
AB  - Colorectal cancer (CRC) is the third most common malignant disease in men and the
      second in women worldwide. CRC relapse occurs mostly in liver and lungs,
      decreasing the 5-year survival to 6 %. Metadherin (MTDH) is overexpressed in
      several types of cancer, has been implicated in proliferation, invasion,
      metastasis, angiogenesis, and chemoresistance, and is a factor of poor prognosis
      in CRC. In this work we addressed the prognostic significance of MTDH expression
      in CRC progression to the lungs. We found that MTDH gene was more frequently
      amplified (copy number >1.8) in patients with CRC and relapse to the lung, when
      compared to patients without lung metastases (17.4 vs 100 %; p < 0.001). We
      observed a correlation between MTDH gene copy number and MTDH expression by IHC
      (p = 0.0001). Next we also analyzed MTDH expression by IHC in samples from 85
      patients diagnosed with CRC, stage II or III, M0, with at least 3 years of follow
      up. Kaplan-Meier survival analysis showed that lung relapse-free survival (HR
      5.29, 95 % CI 1.90-14.77, p = 0.0004), liver relapse-free survival (HR 8.59, 95 %
      CI 0.99-74.18, p = 0.003), relapse-free survival (HR 4.85, 95 % CI 1.88-12.45, p
      = 0.0003) and overall survival (HR 3.75, 95 % CI 1.15-12.18, p = 0.018) were
      significantly lower in the group with high MTDH expression. Multivariate analysis
      showed that high MTDH expression was an independent factor for all outcomes. This
      study demonstrates that high MTDH expression is a biomarker of relapse in CRC,
      including lung-specific relapse. Determination of MTDH expression in primary CRC
      may be useful in the earlier detection of lung metastases in patients with high
      expression and increased risk. 

PMID- 24946953
TI  - [Systematic reviews and meta-analyses].

PMID- 24946952
TI  - Determinants of disease phenotype in trypanosomatid parasites.
AB  - Trypanosomatid parasites infect over 21 million people worldwide, with a range of
      disease phenotypes. Trypanosoma cruzi causes American trypanosomiasis, wherein 30
      40% of infected individuals develop disease manifestations, most commonly
      cardiomyopathy but also digestive megasyndromes. In the case of Trypanosoma
      brucei, the etiological agent of African trypanosomiasis, disease progression can
      be rapid or slow, with early or late central nervous system involvement. Finally,
      Leishmania species cause leishmaniasis, a disease that ranges from self-healing
      but scarring cutaneous lesions to fatal visceral leishmaniasis in which parasites
      disseminate to the liver, spleen, and bone marrow. This review highlights
      parasite factors involved in disease phenotype in all three trypanosomatid
      diseases, with a particular focus on recent advances using large-scale 'omics'
      techniques. 

PMID- 24946954
TI  - Prediction of clinical outcome in advanced hepatitis C-associated liver disease:
      identification of patients at the highest need for antiviral treatment and
      surveillance.

PMID- 24946955
TI  - Targeting of gut specific leucocyte recruitment in IBD by vedolizumab.

PMID- 24946956
TI  - Sonographically guided percutaneous treatment of liver abscesses in critically
      Ill patients.
AB  - BACKGROUND: The management of liver abscess (LA) has shifted toward intravenous
      broad-spectrum antibiotics and image-guided percutaneous needle aspiration (PNA)
      or percutaneous catheter drainage (PCD). AIM: To evaluate the efficacy of
      percutaneous treatment for patients with LA. METHODS: We performed a
      retrospective analysis of 264 patients with 354 LA treated by percutaneous
      management from 1989 to 2012. All patients received appropriate antibiotic
      therapy. Patients with LA <50 mm in diameter were initially treated by
      sonographic-guided PNA and those with LA >=50 mm were initially treated by
      ultrasound ultrasound-guided PCD. Surgery was planned only when there was no
      clinical improvement after the initial nonsurgical treatment. Primary outcome was
      the conversion rate to surgery. Secondary outcomes were mortality, length of
      hospital stay, and the procedure-related complications. RESULTS: PNA was
      performed initially in 116 patients (44%), with 70 of them later requiring PCD
      due to abscess recurrence. In 148 patients (56%), PCD was performed initially.
      PCD was performed twice or more in 63 patients. Percutaneous treatment was the
      definitive and successful treatment in 230 of 264 patients (87.1%). Twenty
      patients (7.7%) were converted to surgery. Twenty-one patients (7.9%) died. The
      median hospital stay was 12 (range, 9-18) days, with complications occurring in
      23 patients (8.7%). CONCLUSIONS: Percutaneous management with systemic
      antibiotics is effective and safe and allows resolution of most LA. However, a
      small proportion of patients with LA still requires surgical drainage.

PMID- 24946957
TI  - Predictive value of PAK6 and PSMB4 expression in patients with localized prostate
      cancer treated with dose-escalation radiation therapy and androgen deprivation
      therapy.
AB  - PURPOSE: The present study analyzed the expression by immunochemistry of the
      novel markers P21-activated protein kinase 6 (PAK6) and proteasome beta-4 subunit
      (PSMB4) in men with localized prostate cancer (PC) who were treated with dose
      escalation radiotherapy (RT) and androgen deprivation therapy. MATERIALS AND
      METHODS: Between 1996 and 2004, a cohort of 129 patients with PC who underwent
      diagnostic biopsies pretreatment and 24 to 36 months following RT were enrolled
      in this study. Suitable archival diagnostic tissue was obtained from 89 patients.
      Median follow-up was 129 months (48-198). Correlation analysis was done to assess
      association between PAK6 and PSMB4 expression and clinical outcome. RESULTS: PAK6
      and PSMB4 were expressed in the cytoplasm in 62% and 96.7% of diagnostic
      biopsies, respectively. Increased staining for PAK6 was significantly (P = 0.04)
      correlated with higher Gleason scores. In the multivariate analysis, the
      intensity of PSMB4 staining was an independent predictor of local relapse (hazard
      ratio = 8.6, P = 0.04). CONCLUSIONS: To our knowledge, this is the first
      description of PAK6 and PSMB4 expression in the diagnostic specimens of men with
      PC who were treated with RT. If confirmed by further studies, increased
      expression of these genes could be used to identify patients at a high risk of
      developing local failure following high-dose RT, thus better tailoring treatments
      for the individual patient.

PMID- 24946958
TI  - Cancer-free survival and local tumor control after impendence-based
      radiofrequency ablation of biopsy-proven renal cell carcinomas with a minimum of
      1-year follow-up.
AB  - OBJECTIVES: There are numerous reports describing the use of radiofrequency
      ablation (RFA) to treat renal cell carcinoma. Many series, however, describe
      heterogeneous populations, lack histologic descriptions, use various RFA systems,
      and indicate tumor destruction by different ablation end points. This study
      examined the outcomes of computed tomography-guided, impedance-based RFA of
      biopsy-proven renal cell carcinoma clinically staged as T1a with a minimum of 1
      year of postablation follow-up. METHODS AND MATERIALS: This retrospective study
      identified all consecutive patients who had undergone renal RFA since May 2005 at
      our institution. Patients without biopsy-proven renal cell carcinoma (RCCa) were
      excluded. Of the patients who met these criteria, evaluation was limited to
      patients with a minimum of 12 months of follow-up. Data collected from the
      patients' electronic medical and radiologic records included demographic data,
      tumor-related data, procedural details, and clinical follow-up visits. RESULTS: A
      total of 39 patients (46 lesions) met the inclusion criteria. The mean tumor
      diameter was 2.6 cm (range: 1.2-4.0 cm). The most common histologies were clear
      cell (n = 27) and papillary (n = 16) renal cancer. The lesion location was
      equally divided between upper pole (n = 16), middle pole (n = 16), and lower pole
      (n = 14). Overall, 83% of the tumors were exophytic. No residual or recurrent
      enhancing mass was identified in the ablation bed on post-RFA imaging during the
      mean follow-up period of 35.3 months (range: 12-83). All patients were treated in
      a single encounter and no lesion required a second ablation; technical success
      (absence of residual tumor) on the initial post-RFA imaging study was 46 of 46
      (100%). Clinical success was achieved in 45 of 46 lesions (98%); residual, viable
      tumor was found in a pretransplant nephrectomy specimen on postprocedure day 127.
      The mean cancer-free survival was 36.2 months. Comparison of preablation and
      postablation renal function found no statistically significant change.
      CONCLUSIONS: The consistent outcomes in our post-RFA imaging and clinical
      surveillance allow us to offer image-guided ablation to patients with T1a RCCa as
      a valid treatment option offering long-term cancer-free survival. Impedance-based
      RFA in a carefully selected patient population with T1a RCCa is a reliable
      treatment option, with disease-free survival rates that are comparable to partial
      nephrectomy.

PMID- 24946959
TI  - Comparison of two fiber-optical temperature measurement systems in magnetic
      fields up to 9.4 Tesla.
AB  - PURPOSE: Precise temperature measurements in the magnetic field are indispensable
      for MR safety studies and for temperature calibration during MR-guided
      thermotherapy. In this work, the interference of two commonly used fiber-optical
      temperature measurement systems with the static magnetic field B0 was determined.
      METHODS: Two fiber-optical temperature measurement systems, a GaAs-semiconductor
      and a phosphorescent phosphor ceramic, were compared for temperature measurements
      in B0 . The probes and a glass thermometer for reference were placed in an MR
      compatible tube phantom within a water bath. Temperature measurements were
      carried out at three different MR systems covering static magnetic fields up to
      B0  = 9.4T, and water temperatures were changed between 25 degrees C and 65
      degrees C. RESULTS: The GaAs-probe significantly underestimated absolute
      temperatures by an amount related to the square of B0 . A maximum difference of
      DeltaT = -4.6 degrees C was seen at 9.4T. No systematic temperature difference
      was found with the phosphor ceramic probe. For both systems, the measurements
      were not dependent on the orientation of the sensor to B0 . CONCLUSION:
      Temperature measurements with the phosphor ceramic probe are immune to magnetic
      fields up to 9.4T, whereas the GaAs-probes either require a recalibration inside
      the MR system or a correction based on the square of B0.

PMID- 24946960
TI  - Proteostasis impairment in protein-misfolding and -aggregation diseases.
AB  - Cells possess an extensive network of components to safeguard proteome integrity
      and maintain protein homeostasis (proteostasis). When this proteostasis network
      (PN) declines in performance, as may be the case during aging, newly synthesized
      proteins are no longer able to fold efficiently and metastable proteins lose
      their functionally active conformations, particularly under conditions of cell
      stress. Apart from loss-of-function effects, a critical consequence of PN
      deficiency is the accumulation of cytotoxic protein aggregates, which are also
      associated with many age-dependent neurodegenerative diseases and other medical
      disorders. Here we discuss recent evidence that the chronic production of
      aberrantly folded and aggregated proteins in these diseases is harmful by
      overtaxing PN capacity, setting in motion a vicious cycle of increasing proteome
      imbalance that eventually leads to PN collapse and cell death. 

PMID- 24946961
TI  - Frontiers in hedgehog signal transduction.

PMID- 24946962
TI  - Control of mRNA turnover: implication of cytoplasmic RNA granules.
AB  - The control of mRNA turnover is essential for the cell to rationalize its mRNA
      content both under physiological conditions and upon stress. Several mechanisms
      involved in the control of mRNA turnover have been elucidated. These include
      surveillance mechanisms such as nonsense-mediated decay, non-stop mediated decay
      and non-go-mediated decay that eliminate aberrant mRNAs, and regulatory
      mechanisms including AU-mediated decay, GU-mediated decay, and CDE-mediated decay
      that ensure mRNA plasticity. In general, the mechanisms of RNA decay rely on
      interactions between specific cis-acting RNA elements and selected RNA-binding
      proteins that either prevent the degradation of mRNA targets or induce the
      recruitment of decaying effectors leading to mRNA degradation. Formation of
      cytoplasmic RNA granules including processing bodies, stress granules, UV
      granules, and exosome granules have recently emerged as an additional mechanism
      that control mRNA turnover of selected mRNAs. Here we will review briefly review
      the main mechanisms that control mRNA decay and highlight possible implication of
      RNA granules in such mechanisms. 

PMID- 24946964
TI  - Promoter-specific alterations of APC are a rare cause for mutation-negative
      familial adenomatous polyposis.
AB  - n familial adenomatous polyposis (FAP), 20% of classical and 70% of
      attenuated/atypical (AFAP) cases remain mutation-negative after routine testing;
      yet, allelic expression imbalance may suggest an APC alteration. Our aim was to
      determine the proportion of families attributable to genetic or epigenetic
      changes in the APC promoter region. We studied 51 unrelated families/cases (26
      with classical FAP and 25 with AFAP) with no point mutations in the exons and
      exon/intron borders and no rearrangements by multiplex ligation-dependent probe
      amplification (MLPA, P043-B1). Promoter-specific events of APC were addressed by
      targeted resequencing, MLPA (P043-C1), methylation-specific MLPA, and Sanger
      sequencing of promoter regions. A novel 132-kb deletion encompassing the APC
      promoter 1B and upstream sequence occurred in a classical FAP family with allele
      specific APC expression. No promoter-specific point mutations or hypermethylation
      were present in any family. In conclusion, promoter-specific alterations are a
      rare cause for mutation-negative FAP (1/51, 2%). The frequency and clinical
      correlations of promoter 1B deletions are poorly defined. This investigation
      provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7
      (14%) for families with allele-specific expression of APC. Clinically, promoter
      1B deletions may associate with classical FAP without extracolonic
      manifestations.

PMID- 24946965
TI  - Glyaderm((r)) dermal substitute: clinical application and long-term results in 55
      patients.
AB  - INTRODUCTION: Glycerol preserved acellular dermis (Glyaderm((r))) consists of
      collagen and elastin fibers and is the first non-profit dermal substitute derived
      from glycerol-preserved, human allogeneic skin. It is indicated for bi-layered
      skin reconstruction of full thickness wounds. METHODS: A protocol for clinical
      application and optimal interval before autografting with split thickness skin
      graft (STSG) was developed in a pilot study. A phase III randomized, controlled,
      paired, intra-individual study compared full thickness defects engrafted with
      Glyaderm((r)) and STSG versus STSG alone. Outcome measures included percentage of
      Glyaderm((r)) take, STSG take, and scar quality assessment. RESULTS: Pilot study
      (27 patients): Mean take rates equaled 91.55% for Glyaderm((r)) and 96.67% for
      STSG. The optimal autografting interval was 6 days (+/-1 day). Randomized trial
      (28 patients): Mean Glyaderm((r)) take rate was 88.17%. STSG take rates were
      comparable for both research groups (p=0.588). One year after wound closure,
      Glyaderm((r))+STSG was significantly more elastic (p=0.003) than STSG alone.
      Blinded observers scored Glyaderm((r)) treated wounds better in terms of scar
      quality. DISCUSSION: The efficacy of Glyaderm((r)) as a suitable dermal
      substitute for full thickness wounds is attested. Currently a procedure for
      simultaneous application of Glyaderm((r)) and STSG is adopted, allowing for
      further widespread use of Glyaderm((r)).

PMID- 24946966
TI  - Comment on: burn care experts and burn expertise.

PMID- 24946967
TI  - A review of treatment strategies for hydrofluoric acid burns: current status and
      future prospects.
AB  - Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive
      effects and systemic toxicity. HF enters the human body via where it contacts,
      such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces.
      In the recent years, the incidence of HF burn has tended to increase over time.
      The injury mechanism of HF is associated primarily with the massive absorption of
      HF and the release of hydrogen ions. Correct diagnosis and timely treatment are
      especially important for HF burns. The critical procedure to treat HF burn is to
      prevent on-going HF absorption, and block the progressive destruction caused by
      fluoride ions. Due to the distinct characteristics of HF burns, the topical
      treatment, as well as systemic support, has been emphasised. Whereas, management
      of patients with HF burns remains a great challenge in some situations. To date,
      there has been no widely accepted protocol for the rescue of HF burns, partly due
      to the diversity of HF burns. This paper overviews the current status and
      problems of treatment strategies for HF burns, for the purpose of promoting the
      future researches and improvement. 

PMID- 24946968
TI  - Who dropped the ball on L-DOPA? A patient's lament.

PMID- 24946969
TI  - Worse long-term survival after off-pump than on-pump coronary artery bypass
      grafting.
AB  - OBJECTIVE: To determine whether off-pump coronary artery bypass grafting (CABG)
      is associated with worse long-term survival compared with on-pump CABG. We
      performed a meta-analysis of adjusted observational studies and randomized
      controlled trials. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of
      Controlled Trials were searched through March 2014. Eligible studies were
      randomized controlled trials and adjusted observational studies (in which
      appropriate statistical methods adjusting for confounders had been used) of off
      pump versus on-pump CABG that had reported long-term (>=5-year) all-cause
      mortality as an outcome. RESULTS: Of 478 potentially relevant studies screened
      initially, 5 randomized trials and 17 observational studies, enrolling a total of
      104,306 patients, were identified and included. A pooled analysis of all 22
      studies demonstrated a statistically significant 7% increase in long-term all
      cause mortality with off-pump relative to on-pump CABG (hazard ratio, 1.07; 95%
      confidence interval, 1.03-1.11; P=.0003). Although a pooled analysis of 5
      randomized trials (1486 patients) demonstrated a statistically nonsignificant 14%
      increase in mortality with off-pump relative to on-pump CABG (hazard ratio, 1.14;
      95% confidence interval, 0.84-1.56; P=.39), another pooled analysis of 17
      observational studies (102,820 patients) demonstrated a statistically significant
      7% increase in mortality with off-pump relative to on-pump CABG (hazard ratio,
      1.07; 95% confidence interval, 1.03-1.11; P=.0004). CONCLUSIONS: A meta-analysis
      of 22 studies, enrolling a total of >100,000 patients, showed that off-pump CABG
      is likely associated with worse long-term (>=5-year) survival compared with on
      pump CABG.

PMID- 24946970
TI  - Historical perspectives of The American Association for Thoracic Surgery: John
      Anton Waldhausen (1929-2012).

PMID- 24946971
TI  - Perceived stress and emotional social support among women who are denied or
      receive abortions in the United States: a prospective cohort study.
AB  - BACKGROUND: Examining women's stress and social support following denial and
      receipt of abortion furthers understanding of the effects of unwanted
      childbearing and abortion on women's well-being. This study investigated
      perceived stress and emotional social support over time among women who were
      denied wanted abortions and who received abortions, and compared outcomes between
      the groups. METHODS: The Turnaway Study is a prospective cohort study of women
      who sought abortions at 30 abortion facilities across the United States, and
      follows women via semiannual phone interviews for five years. Participants
      include 956 English or Spanish speaking women aged 15 and over who sought
      abortions between 2008 and 2010 and whose gestation in pregnancy fit one of three
      groups: women who presented up to three weeks beyond a facility's gestational age
      limit and were denied an abortion; women presenting within two weeks below the
      limit who received an abortion; and women who received a first trimester
      abortion. The outcomes were modified versions of the Perceived Stress Scale and
      the Multidimensional Scale of Perceived Social Support. Longitudinal mixed
      effects models were used to assess differences in outcomes between study groups
      over 30 months. RESULTS: Women denied abortions initially had higher perceived
      stress than women receiving abortions near gestational age limits (1.0 unit
      difference on 0-16 scale, P = 0.003). Women receiving first-trimester abortions
      initially had lower perceived stress than women receiving abortions near
      gestational age limits (0.6 difference, P = 0.045). By six months, all groups'
      levels of perceived stress were similar, and levels remained similar through 30
      months. Emotional social support scores did not differ among women receiving
      abortions near gestational limits versus women denied abortions or women having
      first trimester abortions initially or over time. CONCLUSIONS: Soon after being
      denied abortions, women experienced higher perceived stress than women who
      received abortions. The study found no longer-term differences in perceived
      stress or emotional social support between women who received versus were denied
      abortions.

PMID- 24946972
TI  - Impact of dosimetric parameters on local control for patients treated with three
      dimensional pulsed dose-rate brachytherapy for cervical cancer.
AB  - PURPOSE: To investigate the impact of dose-volume histograms parameters on local
      control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy
      (BT). METHODS AND MATERIALS: Within a French multicentric prospective study, the
      data of the 110 patients treated for cervical cancer with external beam
      radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were
      analyzed. Delineation procedures were performed on magnetic resonance imaging in
      a minority of cases and on CT for the majority of cases, adapted from the
      Gynaecological Groupe Europeen de Curietherapie-European Society for Therapeutic
      Radiology and Oncology recommendations. Optimization procedure was left to the
      discretion of the treating center. RESULTS: At 2 years, local control rate
      reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk
      clinical target volume (IR-CTV) V60 were predictive factors for local control (p
      = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75%
      had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4
      11.1). There was no correlation found between the high-risk clinical target
      volume dosimetric parameters and local control. CONCLUSIONS: This multicentric
      study has shown that 3D image-based BT provides a high local control rate for
      cervical cancer patients. The V60 for IR-CTV was identified as an important
      predictive factor for local control.

PMID- 24946975
TI  - Dysplasia-like epithelial atypia in ischemic bowel disease.
AB  - Inflammatory and reactive conditions are known to mimic dysplasia or malignancy
      in the gastrointestinal tract. Epithelial atypia that closely mimics low-grade
      dysplasia (LGD) or high-grade dysplasia (HGD) can sometimes be seen in ischemic
      bowel. To study this phenomenon, we evaluated surgical resections for ischemic
      enteritis (n = 65) and ischemic colitis (n = 99) that included sections of viable
      epithelium adjacent to necrosis. Viable epithelium was classified as normal,
      obviously reactive, LGD-like atypia or high-grade dysplasia (HGD)-like atypia.
      Cases with available paraffin blocks were characterized immunohistochemically
      with antibodies to p16, p53, and MIB-1. Fourteen dysplastic lesions in chronic
      ulcerative colitis served as controls. Dysplasia-like atypia was found in 13
      small bowel resections (20%) and 15 colectomies (15%), most common near re
      epithelializing erosions. Two colectomies had extensive dysplasia-like atypia,
      whereas the other 26 demonstrated focal or several foci of atypia. Nine cases
      contained HGD-like atypia, 15 contained LGD-like atypia, and 4 showed both HGD-
      and LGD-like atypia. Features indicating subacute-to-chronic ischemia were more
      frequent in LGD-like atypia (13/15, 87%) than HGD-like atypia (2/9, 22%; P =
      .003). Dysplasia-like atypia showed overexpression of p16 (73%), p53 (50%), and
      MIB-1 (92%), but these markers did not reliably distinguish dysplasia-like atypia
      from true dysplasia in chronic ulcerative colitis (P = .45 for p16, P = .51 for
      p53, P = .08 for MIB-1). These results underscore the frequency of dysplasia-like
      atypia in ischemic bowel, which can occasionally be an extensive and worrisome
      finding. Distinction from true dysplasia requires recognizing the context of the
      epithelial atypia because cell cycle markers were not helpful in classifying
      individual cases. 

PMID- 24946973
TI  - Is oncoplastic surgery a contraindication for accelerated partial breast
      radiation using the interstitial multicatheter brachytherapy method?
AB  - PURPOSE: To evaluate accelerated partial breast irradiation (APBI) in patients
      after oncoplastic surgery for early breast cancer. METHODS AND MATERIALS: A
      retrospective analysis of 136 breasts of 134 patients, who received breast
      conserving oncoplastic surgery for low-risk breast cancer between 2002 and 2010
      in the Universities of Vienna and Luebeck followed by adjuvant APBI applying
      total doses of pulse dose rate of 50.4 Gy or high-dose rate (HDR) of 32 Gy over 4
      days. Target volume definition was performed by the use of surgical-free margin
      data, related to intraoperatively fixed clip positions, pre- and postoperative
      imaging, and palpation. RESULTS: At the time of data acquisition, 131 of 134
      patients were alive. The median follow-up time was 39 months (range, 4-106
      months). After high-dose rate treatment, 3 of 89 patients showed systemic
      progress after a mean follow-up of 47 months (range, 19-75 months) and 2 patients
      had a different quadrant in-breast tumor after 27 and 35 months. One patient died
      7 months after treatment of unknown causes. After pulse dose rate treatment, 1 of
      45 patients had a local recurrence after 42 months and 1 patient died because of
      another cause after 13 months. We observed mild fibrosis in 27 breasts,
      telangiectasia in 6, hyperpigmentation in 14 cases, and keloid formation in 1.
      CONCLUSIONS: These preliminary results suggest the feasibility of multicatheter
      APBI after oncoplastic breast-conserving surgery in selected low-risk breast
      cancer patients; however, special attention to target volume definition is
      needed. Further prospective investigations with long follow-up are needed to
      define the real value of the procedure.

PMID- 24946974
TI  - Identification of a major causative agent of human cercarial dermatitis,
      Trichobilharzia franki (Muller and Kimmig 1994), in southern England and its
      evolutionary relationships with other European populations.
AB  - BACKGROUND: Trichobilharzia is the most species rich and widely distributed genus
      of schistosomes and is known throughout Europe and North America as an agent of
      human cercarial dermatitis. The disease is caused by an acute allergic reaction
      in the skin that develops as a consequence of repeated contact with water
      containing schistosomatid cercariae. However, despite historical outbreaks of the
      disease, there are no published records of accurately identified Trichobilharzia
      species from the UK. METHODS: Two hundred Radix auricularia (L.) were sampled
      from a recreational fishing lake in Hampshire and emerging schistosomatid
      cercariae were collected for microscopy and DNA extraction. General morphological
      description of the cercariae was performed, alongside sequencing and phylogenetic
      analysis of the 28S ribosomal DNA for accurate species identification as well as
      comparisons of ITS1 in order to identify evolutionary affinities with other
      European populations. All molecular comparisons were performed using published
      sequences. RESULTS: The phylogenetic analysis of 28S sequences identified the
      cercariae as Trichobilharzia franki. Two unique British ITS1 haplotypes were
      identified which were most closely related to haplotypes of T. franki populations
      from France. Haplotype network analysis indicated the mixing of T. franki
      populations throughout Europe. It is suggested that parasite distribution is the
      probable result of the movement of migratory waterfowl. CONCLUSIONS: This is the
      first accurate record of T. franki in the UK. The movement of T. franki with
      waterfowl could pose a considerable human health risk, as in mainland Europe, and
      signifies T. franki-associated human cercarial dermatitis as a re-emerging
      disease in the UK.

PMID- 24946976
TI  - Diet variation of a generalist fish predator, grey snapper Lutjanus griseus,
      across an estuarine gradient: trade-offs of quantity for quality?
AB  - This study examined diet, prey quality and growth for a generalist fish predator,
      grey snapper Lutjanus griseus, at five sites across an estuarine gradient in the
      Loxahatchee River estuary, Florida, U.S.A. Lutjanus griseus diets shifted from
      dominance by low quality, intertidal crabs upstream to an increased reliance on
      higher quality shrimp, fishes and benthic crabs downstream. Frequency of L.
      griseus with empty stomachs was higher at downstream sites. Lutjanus griseus
      growth rates did not vary among sites. Results indicate that L. griseus may be
      able to compensate for lower quality prey upstream by consuming more, and thus
      individuals are able to maintain similar levels of energy balance and growth
      rates across the estuarine gradient. Elucidating mechanisms, such as compensatory
      feeding, that enable generalist species to remain successful across habitat
      conditions are critical to understanding their organismal ecology and may
      facilitate predictions about the response of generalists to landscape alteration.

PMID- 24946977
TI  - Suicide on railroad rights-of-way: a psychological autopsy study.
AB  - Findings from 55 psychological autopsies of decedents who perished on U.S.
      railroad rights-of-way between October 1, 2007, and September 30, 2010 are
      reported. Described are distal, proximal, and contextual factors of risk;
      understandings of why these suicides occurred on railroad rights-of-way; and
      opportunities for prevention of similar suicides. International comparisons of
      suicides on railroad rights-of-way are made to highlight distinct findings
      regarding U.S. cases. Decedents studied exhibited considerable predisposing risk
      for suicide, with a high prevalence of severe mental disorders and substance
      abuse. In addition, a number of acute risk factors were commonly observed,
      notably suicide ideation, hopelessness, anxiety, and anger. In the context of
      that acute risk, associated situational variables and a relative absence of
      protective factors are described. 

PMID- 24946978
TI  - Molecular basis for substrate recognition by lysine methyltransferases and
      demethylases.
AB  - Lysine methylation has emerged as a prominent covalent modification in histones
      and non-histone proteins. This modification has been implicated in numerous
      genomic processes, including heterochromatinization, cell cycle progression, DNA
      damage response, DNA replication, genome stability, and epigenetic gene
      regulation that underpins developmental programs defining cell identity and fate.
      The site and degree of lysine methylation is dynamically modulated through the
      enzymatic activities of protein lysine methyltransferases (KMTs) and protein
      lysine demethylases (KDMs). These enzymes display distinct substrate
      specificities that in part define their biological functions. This review
      explores recent progress in elucidating the molecular basis of these
      specificities, highlighting structural and functional studies of the
      methyltransferases SUV4-20H1 (KMT5B), SUV4-20H2 (KMT5C), and ATXR5, and the
      demethylases UTX (KDM6A), JMJD3 (KDM6B), and JMJD2D (KDM4D). We conclude by
      examining these findings in the context of related KMTs and KDMs and by exploring
      unresolved questions regarding the specificities and functions of these enzymes.

PMID- 24946979
TI  - Cytotoxicity of alloying elements and experimental titanium alloys by WST-1 and
      agar overlay tests.
AB  - OBJECTIVE: This study was performed to evaluate the biocompatibility of nine
      types of pure metals using 36 experimental prosthetic titanium-based alloys
      containing 5, 10, 15, and 20wt% of each substituted metal. METHODS: The cell
      viabilities for pure metals on Ti alloys that contain these elements were
      compared with that of commercially pure (CP) Ti using the WST-1 test and agar
      overlay test. RESULTS: The ranking of pure metal cytotoxicity from most potent to
      least potent was: Co>Cu>In>Ag>Cr>Sn>Au>Pd>Pt>CP Ti. The cell viability ratios for
      pure Co, Cu, In, and Ag were 13.9+/-4.6%, 21.7+/-10.4%, 24.1+/-5.7%, and 24.8+/
      6.0%, respectively, which were significantly lower than that for the control
      group (p<0.05). Pure Pd and Pt demonstrated good biocompatibility with cell
      viabilities of 93.8+/-9.6% and 97.2+/-7.1%, respectively. The Ti-5Pd alloy
      exhibited the highest cell viability (128.4+/-21.4%), which was greater than that
      of CP Ti. By alloying pure Co or Cu with Ti, the cell viabilities for the Ti-xCo
      and Ti-xCu alloys increased significantly up to 10wt% of the alloying element
      followed by a gradual decrease with a further increase in the concentration of
      the alloying element. Based on the agar overlay test, pure Ag, Co, Cr, Cu, and In
      were ranked as 'moderately cytotoxic', whereas all Ti alloys were ranked as
      'noncytotoxic'. SIGNIFICANCE: The cytotoxicity of pure Ag, Co, Cr, Cu, and In
      suggests a need for attention in alloy design. The cytotoxicity of alloying
      elements became more biocompatible when they were alloyed with titanium. However,
      the cytotoxicity of titanium alloys was observed when the concentration of the
      alloying element exceeded its respective allowable limit. The results obtained in
      this study can serve as a guide for the development of new Ti-based alloy
      systems.

PMID- 24946980
TI  - Correlation between polymerization stress and interfacial integrity of composites
      restorations assessed by different in vitro tests.
AB  - OBJECTIVE: to correlate polymerization stress data obtained under two compliance
      conditions with those from different interfacial quality tests. METHODS: Six
      commercial composites were tested (Filtek Z250/3M ESPE, Heliomolar/Ivoclar
      Vivadent, Aelite LS Posterior/Bisco, Filtek Supreme/3M ESPE, ELS/Saremco and
      Venus Diamond/Heraeus Kulzer). Bond strength (BS) was evaluated by push-out test
      on slices of bovine dentin (2-mm thick) with tapered cavities. For microleakage
      (ML) and gap analysis, cylindrical cavities in bovine incisors (4-mm diameter and
      1.5-mm height) were restored and epoxy replicas of the cavo-surface margins were
      prepared for analysis under scanning electron microscopy (200*). The same
      specimens were submitted to a microleakage protocol using AgNO3 as tracer. After
      sectioned twice perpendicularly, ML was determined under a stereomicroscope
      (60*). Polymerization stress (PS, n=5) was determined by the insertion of the
      composite (h=1.5mm) between poly(methyl methacrylate), PMMA, or glass rods (O=4
      mm) attached to a universal testing machine. Data were analyzed using Kruskal
      Wallis (ML and gaps), and ANOVA/Tukey (BS and PS, alpha=5%). Pearson's
      correlation test was used to verify correlations between stress and interfacial
      quality. RESULTS: BS varied from 4.7 to 7.9 MPa. Average ML data ranged from 0.34
      to 0.89 mm. Maximum ML varied from 0.61 to 1.34 mm. Gap incidence varied from 13
      to 47%. PS ranged from 2.5 to 4.4 MPa in PMMA, and between 2.1 and 8.2 in glass.
      Statistically significant correlations were observed between stress and
      interfacial quality, except between BS and PS in glass. These correlations were
      stronger when PMMA was used as bonding substrate. CONCLUSIONS: PS data obtained
      using a high compliance testing system showed a stronger correlation with "in
      vitro" interfacial integrity results, compared to data from a low compliance
      system.

PMID- 24946981
TI  - Micro-Raman spectroscopic analysis of TiO2 phases on the root surfaces of
      commercial dental implants.
AB  - OBJECTIVES: To identify the TiO2 phases of the root surface of commercially
      available titanium dental implants, subjected to various surface treatments.
      METHODS: The titanium implants studied were: Allfit (ALF), Ice (ICE), IMZ TPS
      (TPS), Laser Lok (LLK), Prima Connex (PRC), Ospol (OSP), Osseospeed TX (OSS),
      Osseotite Full (OTF), Replace Select (RPS), SLA (SLA) and Trilobe (TRB). The root
      parts of the implants (n:2) were analyzed by Raman microspectroscopy employing
      argon ion laser excitation (514.5nm wavelength) and a 100 MUm * 100 MUm sampling
      area at two randomly selected sites. RESULTS: The spectra of OSP and RPS showed
      the characteristic peaks of anatase, with traces of rutile (RPS). Complex phases
      composed of anatase, rutile and amorphous TiO2 were identified in ALF, ICE and
      LLK. Rutile and amorphous TiO2 were found in PRC, OSS, OTF, TPS and TRB, whereas
      rutile and possibly brookite were traced in SLA. In all implants, except OSP and
      RPS, peaks assigned to organic impurities (CH2, CH3) and carbonates were
      recorded. Ti2O3 was identified in OTF, PRC and Al2O3 in TRB. SIGNIFICANCE: Great
      variations in the TiO2 polymorphs were registered among the implant root surfaces
      tested. Considering the important differences in the biological activity of these
      polymorphs, it can be concluded that provision of information regarding the TiO2
      state on implant surfaces should be a mandatory task for implant manufacturers.

PMID- 24946982
TI  - One-year evaluation of two hybrid composites placed in a randomized-controlled
      clinical trial.
AB  - OBJECTIVE: The aim of this prospective randomized-controlled clinical trial is to
      assess the long-term performance of two direct composite resins in posterior
      teeth. This study provides a survey of the one-year results. MATERIALS AND
      METHODS: A total of 1805 restorations were placed by students in stress-bearing
      Class I/II cavities (including cuspal-coverage) in molars and premolars in 456
      patients. Clinical evaluation was performed at baseline and after one year using
      modified USPHS criteria. The restorations in each patient were performed either
      with Ceram X/Prime&Bond NT or Tetric Ceram/Optibond Solo Plus. RESULTS: After one
      year 528 fillings with Ceram X and 580 with Tetric Ceram were available for
      evaluation of substance loss, contact point, color match, marginal staining,
      marginal adaptation, secondary caries and radiographic examination (if
      necessary). This represents a recall rate of 61.18% (279 patients). The failure
      rate per material was 5.3% in the Ceram X group and 6.1% in the Tetric Ceram
      group. Most of the failures were associated with marginal adaptation/integrity of
      the filling. A significant influence on the occurrence of a failure was observed
      for the number of treated teeth per patient, the age of the patient, the mesio
      distal extension of the restoration and the tooth position. Gender, material, a
      previous root canal treatment, the bucco-lingual extension of the filling or
      cuspal-coverage did not significantly influence the failure rate. Patients
      attending the first recall were significantly older and had more fillings than
      patients not attending. CONCLUSIONS: In a group of Class I/II restorations
      (including cuspal-coverage), there was no significant difference in failure rates
      between ormocer-based and bis-GMA-based restorative systems after one year. A
      previous root canal treatment had no negative influence on the failure rate. A
      longer observation period is indicated to get clear evidence of the long-term
      performance of these composite resin systems.

PMID- 24946983
TI  - Sealing performance of resin cements before and after thermal cycling: evaluation
      by optical coherence tomography.
AB  - OBJECTIVES: Self-adhesive resin cements have been recently introduced; however,
      there is little data available on their long-term performance. In this in vitro
      study, swept-source optical coherence tomography (OCT) at 1310 nm center
      wavelength was used for monitoring adaptation of indirect resin restorations
      after thermal cycling. METHODS: Resin inlays were luted to class-I cavities of
      extracted human teeth using three resin cements; Clearfil SA Luting (SA;
      Kuraray), Bistite II DC or Multibond II (Tokuyama Dental). Each cement was
      applied with or without pre-coating of dentin by a self-etch adhesive (Clearfil
      SE Bond) and a low-viscosity microfilled resin. OCT imaging was performed after
      24 h, after 2000 and after 10,000 thermocycles (n=5). Selected samples were
      sectioned for interfacial observation by confocal laser scanning microscope
      (CLSM). Floor adaptation (percentage) was analyzed by software on 20 B-scans
      throughout each specimen, and subjected to statistical analysis by three-way
      ANOVA test at a significance level of 0.05. RESULTS: Resin cement type, resin
      coating and thermal aging all significantly affected adaptation (p<0.05).
      Initially, SA showed the highest adaptation; however, thermal aging significantly
      affected its sealing. The best results for all the cements were consistently
      achieved when the resin coating technique was applied where no deterioration of
      interfacial integrity was observed in the coated groups. CLSM closely confirmed
      OCT findings in all groups. SIGNIFICANCE: OCT could be used for monitoring of
      composite inlays with several interfacial resin layers. The application of a
      direct bonding agent in the resin-coating technique improved interfacial sealing
      and durability of all resin cements.

PMID- 24946985
TI  - The nitrogen cycle in cryoconites: naturally occurring nitrification
      denitrification granules on a glacier.
AB  - Cryoconites are microbial aggregates commonly found on glacier surfaces where
      they tend to take spherical, granular forms. While it has been postulated that
      the microbes in cryoconite granules play an important role in glacier ecosystems,
      information on their community structure is still limited, and their functions
      remain unclear. Here, we present evidence for the occurrence of nitrogen cycling
      in cryoconite granules on a glacier in Central Asia. We detected marker genes for
      nitrogen fixation, nitrification and denitrification in cryoconite granules by
      digital polymerase chain reaction (PCR), while digital reverse transcription PCR
      analysis revealed that only marker genes for nitrification and denitrification
      were abundantly transcribed. Analysis of isotope ratios also indicated the
      occurrence of nitrification; nitrate in the meltwater on the glacier surface was
      of biological origin, while nitrate in the snow was of atmospheric origin. The
      predominant nitrifiers on this glacier belonged to the order Nitrosomonadales, as
      suggested by amoA sequences and 16S ribosomal RNA pyrosequencing analysis. Our
      results suggest that the intense carbon and nitrogen cycles by nitrifiers,
      denitrifiers and cyanobacteria support abundant and active microbes on the Asian
      glacier.

PMID- 24946984
TI  - Functionalizing a dentin bonding resin to become bioactive.
AB  - OBJECTIVES: To investigate chemo-mechanical effects of incorporating alkaline
      bioactive glass nanoparticles into a light-curable dental resin matrix. METHODS:
      An unfilled Bis-GMA/TEGDMA material was infiltrated with up to 20 wt% of
      ultrafine SiO2-Na2O-CaO-P2O5-Bi2O3 particles. The unfilled and filled resins were
      investigated regarding their viscosity before setting and compared to
      commercially available materials. Set specimens were immersed for 21 days in
      phosphate buffered saline at 37 degrees C. Water uptake, pH, Knoop hardness, and
      degree of conversion of freshly polymerized and stored samples were investigated.
      Resin surfaces were viewed and mapped in a scanning electron microscope for the
      formation of calcium phosphate (Ca/P) precipitates. In addition, Raman
      spectroscopy was performed. Numeric values were statistically compared (p<0.01).
      RESULTS: Viscosity increased with particle loading, but remained below that of a
      flowable dental composite material. Water uptake into and pH induction from the
      polymerized samples also increased with particle loading (p<0.01). The addition
      of 20 wt% nanoparticles had no significant influence on microhardness, yet it
      slightly (p<0.01) increased the degree of conversion after 21 days. Ca/P
      precipitates formed on specimens filled with 20 wt% of the particles, while they
      were scarce on counterparts loaded with 10 wt%, and absent on unfilled resin
      surfaces. SIGNIFICANCE: The results of the current study show that a Bis-GMA
      based resin can be functionalized using alkaline nanoparticles. A material with
      bioactive properties and similar hardness as the unfilled resin was obtained by
      incorporating 20wt% of ultrafine SiO2-Na2O-CaO-P2O5-Bi2O3 particles into the
      resin matrix.

PMID- 24946987
TI  - Ventricular fibrillation triggered by PVCs from papillary muscles: clinical
      features and ablation.
AB  - BACKGROUND: Animal studies showed that papillary muscles can be sources of
      ventricular fibrillation (VF) in both the left and right ventricle, but this
      occurrence in humans has been described only in patients with ischemic heart
      disease. OBJECTIVE: To investigate the role of papillary muscle premature
      ventricular contractions (PVCs) as triggers for VF and the safety and feasibility
      of catheter ablation in these patients. METHODS: Six patients (2 male; age, 40 +/
      11 years; 5 with a normal structural heart and 1 with nonischemic
      cardiomyopathy) with history of VF resulting in repetitive implantable
      cardioverter defibrillator shocks, despite antiarrhythmic drug therapy, and a
      papillary muscle focus of PVCs triggering VF were included and underwent mapping
      and ablation of PVCs. RESULTS: PVCs were observed to trigger VF and localized by
      mapping the earliest activation point that matched pace mapping of the same area.
      In 2 patients, PVCs originated from the left ventricle at the posteromedial
      papillary muscle; in 4 patients, PVCs originated from the right ventricle, at the
      posterolateral papillary muscle. Elimination of the triggering PVC was obtained
      in these areas after 19 +/- 12 minutes by radiofrequency application. During a
      follow-up of 58 +/- 11 months using ambulatory monitoring and defibrillator
      memory interrogation, no patients had recurrence of symptomatic ventricular
      arrhythmias. CONCLUSION: Papillary muscles from both ventricles represent an
      anatomic structure potentially involved in the onset of VF, also in normal
      structural heart. PVCs arising from this area can be successfully eliminated by
      radiofrequency ablation, resulting in freedom from recurrent VF at long-term
      follow-up.

PMID- 24946986
TI  - Oncogenic role and therapeutic target of leptin signaling in colorectal cancer.
AB  - INTRODUCTION: Obesity is characterized by high secretion of several cytokines
      from adipose tissue and is a recognized risk factor for many cancers. Among these
      cytokines, leptin mainly produced by adipose tissue and cancer cells is the most
      studied adipokine. Leptin is an activator of cell proliferation, an antiapoptotic
      molecule and inducer of cancer stem cells in many cell types, and its critical
      roles in obesity-related tumorigenesis are based on its oncogenic, mitogenic, pro
      inflammatory and pro-angiogenic actions. AREAS COVERED: These leptin-induced
      signals and action are critical for their biological effects on energy balance,
      adiposity, endocrine systems, immunity, angiogenesis as well as oncogenesis. This
      review focuses on the up-to-date knowledge on the oncogenic role of leptin
      signaling, clinical significance and specific drug target development in
      colorectal cancer (CRC). Additionally, leptin-induced angiogenic ability and
      molecular mechanisms in CRC cells are discussed. EXPERT OPINION: Stringent
      binding affinity of leptin/Ob-R and overexpression of leptin/Ob-R and their
      targets in cancer cells make it a unique drug target for prevention and treatment
      of CRC, particularly in obesity colorectal patients.

PMID- 24946988
TI  - Plant single-cell and single-cell-type metabolomics.
AB  - In conjunction with genomics, transcriptomics, and proteomics, plant metabolomics
      is providing large data sets that are paving the way towards a comprehensive and
      holistic understanding of plant growth, development, defense, and productivity.
      However, dilution effects from organ- and tissue-based sampling of metabolomes
      have limited our understanding of the intricate regulation of metabolic pathways
      and networks at the cellular level. Recent advances in metabolomics
      methodologies, along with the post-genomic expansion of bioinformatics knowledge
      and functional genomics tools, have allowed the gathering of enriched information
      on individual cells and single cell types. Here we review progress, current
      status, opportunities, and challenges presented by single cell-based metabolomics
      research in plants. 

PMID- 24946989
TI  - Alien plants confront expectations of climate change impacts.
AB  - The success of alien plants in novel environments questions basic assumptions
      about the fate of native species under climate change. Aliens generally spread
      faster than the velocity of climate change, display considerable phenotypic
      plasticity as well as adaptation to new selection pressures, and their ranges are
      often shaped by biotic rather than climatic factors. Given that many native
      species also exhibit these attributes, their risk of extinction as a result of
      climate change might be overestimated. 

PMID- 24946990
TI  - Staring us in the face? An embodied theory of innate face preference.
AB  - Human expertise in face perception grows over development, but even within
      minutes of birth, infants exhibit an extraordinary sensitivity to face-like
      stimuli. The dominant theory accounts for innate face detection by proposing that
      the neonate brain contains an innate face detection device, dubbed 'Conspec'.
      Newborn face preference has been promoted as some of the strongest evidence for
      innate knowledge, and forms a canonical stage for the modern form of the nature
      nurture debate in psychology. Interpretation of newborn face preference results
      has concentrated on monocular stimulus properties, with little mention or focused
      investigation of potential binocular involvement. However, the question of
      whether and how newborns integrate the binocular visual streams bears directly on
      the generation of observable visual preferences. In this theoretical paper, we
      employ a synthetic approach utilizing robotic and computational models to draw
      together the threads of binocular integration and face preference in newborns,
      and demonstrate cases where the former may explain the latter. We suggest that a
      system-level view considering the binocular embodiment of newborn vision may
      offer a mutually satisfying resolution to some long-running arguments in the
      polarizing debate surrounding the existence and causal structure of newborns'
      'innate knowledge' of faces. 

PMID- 24946991
TI  - Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin
      gallate on cognitive function and mood: a systematic review and meta-analysis.
AB  - A systematic review and meta-analysis was conducted on 11 randomized placebo
      controlled human studies of acute effects of tea constituents L-theanine and
      epigallocatechin gallate, administered alone or in combination with caffeine, on
      cognitive function and mood. The outcome measures of mood were alertness,
      calmness, and contentedness, derived from the Bond-Lader scales, and state
      anxiety, from the State-Trait Anxiety Inventory. Cognitive measures assessed were
      attentional switch, intersensory attention, and rapid visual information
      processing. Standardized mean differences between placebo and treatment groups
      are presented for each study and outcome measure. Meta-analysis using a random
      effects model was conducted when data were available for three or more studies.
      Evidence of moderate effect sizes in favor of combined caffeine and L-theanine in
      the first 2 hours postdose were found for outcome measures Bond-Lader alertness,
      attentional switching accuracy, and, to a lesser extent, some unisensory and
      multisensory attentional outcomes. Moderator analysis of caffeine and L-theanine
      doses revealed trends toward greater change in effect size for caffeine dose than
      for L-theanine dose, particularly during the first hour postdose. 

PMID- 24946992
TI  - Effect of Michael adduction on peptide preservation in natural waters.
AB  - The reaction of peptides with chemicals already present in natural waters (such
      as polycyclic aromatic hydrocarbons) is one method that has been suggested to
      preserve peptides for the longer term. In this study we test whether the reaction
      of tetrapeptides with a model quinone can help stabilise the peptide in one
      polluted riverine system, Elizabeth River in Virginia, USA. We found that there
      is almost no difference in rate constants between the peptide and its quinone
      adduct (e.g. 6.62 versus 6.86 per day for AVFA and its respective adduct).
      However, when monitoring the removal of the adduct from natural water, we
      identified two new compounds that are formed as a result of its decomposition.
      Using tandem mass spectrometry we identified potential structures and mechanisms
      for the formation of these new compounds. These new compounds are more
      recalcitrant than their parent peptide-quinone adduct, since they remain in
      solution for 3-10 times longer. Based on our findings we postulate that the
      reaction of peptides with quinones can help preserve sections of the original
      peptide following an initial rearrangement of the original adduct, potentially
      explaining why seemingly labile peptides are observed in most natural waters. 

PMID- 24947000
TI  - Evaluation of team lifting on work demands, workload and workers' evaluation: an
      observational field study.
AB  - The objective of this study was to assess differences in work demands, energetic
      workload and workers' discomfort and physical effort in two regularly observable
      workdays in ironwork; one where loads up to 50kg were handled with two persons
      manually (T50) and one where loads up to 100kg were handled manually with four
      persons (T100). Differences between these typical workdays were assessed with an
      observational within-subject field study of 10 ironworkers. No significant
      differences were found for work demands, energetic workload or discomfort between
      T50 and T100 workdays. During team lifts, load mass exceeded 25kg per person in
      57% (T50 workday) and 68% (T100 workday) of the lifts. Seven ironworkers rated
      team lifting with two persons as less physically demanding compared with lifting
      with four persons. When loads heavier than 25kg are lifted manually with a team,
      regulations of the maximum mass weight are frequently violated. STATEMENT OF
      RELEVANCE: Loads heavier than 25kg are frequently lifted during concrete
      reinforcement work and should be lifted by a team of persons. However, the field
      study showed that loads above 25kg are most of the time not lifted with the
      appropriate number of workers. Therefore, loads heavier than 25kg should be
      lifted mechanically.

PMID- 24947001
TI  - Practitioner versus analyst methods: a nuclear decommissioning case study.
AB  - A requirement arose during decommissioning work at a UK Magnox Nuclear Power
      Station to identify the hazards involved in removing High Dose Rate Items from a
      Cartridge Cooling Pond. Removing objects from the cooling pond under normal
      situations is a routine event with well understood risks but the situation
      described in this paper is not a routine event. The power station has shifted
      from an operational phase in its life-cycle to a decommissioning phase, and as
      such the risks, and procedures to deal with them, have become more novel and
      uncertain. This raises an important question. Are the hazard identification
      methods that have proven useful in one phase of the system lifecycle just as
      useful in another, and if not, what methods should be used? An opportunity arose
      at this site to put the issue to a direct test. Two methods were used, one
      practitioner focussed and in widespread use during the plant's operational phase
      (the Structured What-If method), the other was an analyst method (Cognitive Work
      Analysis). The former is proven on this site but might not be best suited to the
      novelty and uncertainty brought about by a shift in context from operations to
      decommissioning. The latter is not proven on this site but it is designed for
      novelty and uncertainty. The paper presents the outcomes of applying both methods
      to a real-world hazard identification task. 

PMID- 24947002
TI  - Social influence in a virtual tunnel fire--influence of conflicting information
      on evacuation behavior.
AB  - Evacuation from a smoke filled tunnel requires quick decision-making and swift
      action from the tunnel occupants. Technical installations such as emergency
      signage aim to guide tunnel occupants to the closest emergency exits. However,
      conflicting information may come from the behavior of other tunnel occupants. We
      examined if and how conflicting social information may affect evacuation in terms
      of delayed and/or inadequate evacuation decisions and behaviors. To this end,
      forty participants were repeatedly situated in a virtual reality smoke filled
      tunnel with an emergency exit visible to one side of the participants. Four
      social influence conditions were realized. In the control condition participants
      were alone in the tunnel, while in the other three experimental conditions a
      virtual agent (VA) was present. In the no-conflict condition, the VA moved to the
      emergency exit. In the active conflict condition, the VA moved in the opposite
      direction of the emergency exit. In the passive conflict condition, the VA stayed
      passive. Participants were less likely to move to the emergency exit in the
      conflict conditions compared to the no-conflict condition. Pre-movement and
      movement times in the passive conflict condition were significantly delayed
      compared to all other conditions. Participants moved the longest distances in the
      passive conflict condition. These results support the hypothesis that social
      influence affects evacuation behavior, especially passive behavior of others can
      thwart an evacuation to safety. 

PMID- 24947003
TI  - Discomfort of seated persons exposed to low frequency lateral and roll
      oscillation: effect of seat cushion.
AB  - The discomfort caused by lateral oscillation, roll oscillation, and fully roll
      compensated lateral oscillation has been investigated at frequencies between 0.25
      and 1.0 Hz when sitting on a rigid seat and when sitting on a compliant cushion,
      both without a backrest. Judgements of vibration discomfort and the transmission
      of lateral and roll oscillation through the seat cushion were obtained with 20
      subjects. Relative to the rigid seat, the cushion increased lateral acceleration
      and roll oscillation at the lower frequencies and also increased discomfort
      during lateral oscillation (at frequencies less than 0.63 Hz), roll oscillation
      (at frequencies less than 0.4 Hz), and fully roll-compensated lateral oscillation
      (at frequencies between 0.315 and 0.5 Hz). The root-sums-of-squares of the
      frequency-weighted lateral and roll acceleration at the seat surface predicted
      the greater vibration discomfort when sitting on the cushion. The frequency
      dependence of the predicted discomfort may be improved by adjusting the frequency
      weighting for roll acceleration at frequencies between 0.25 and 1.0 Hz. 

PMID- 24947004
TI  - Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis,
      treatment and follow-up.
AB  - Squamous cell carcinoma of the anus (SCCA) is a rare cancer but its incidence is
      increasing throughout the world, and is particularly high in the human
      immunodeficiency virus positive (HIV+) population. A multidisciplinary approach
      is mandatory (involving radiation therapists, medical oncologists, surgeons,
      radiologists and pathologists). SCCA usually spreads in a loco-regional manner
      within and outside the anal canal. Lymph node involvement at diagnosis is
      observed in 30-40% of cases while systemic spread is uncommon with distant
      extrapelvic metastases recorded in 5-8% at onset, and rates of metastatic
      progression after primary treatment between 10% and 20%. SCCA is strongly
      associated with human papilloma virus (HPV, types 16-18) infection. The primary
      aim of treatment is to achieve cure with loco-regional control and preservation
      of anal function, with the best possible quality of life. Treatment dramatically
      differs from adenocarcinomas of the lower rectum. Combinations of 5FU-based
      chemoradiation and other cytotoxic agents (mitomycin C) have been established as
      the standard of care, leading to complete tumour regression in 80-90% of patients
      with locoregional failures in the region of 15%. There is an accepted role for
      surgical salvage. Assessment and treatment should be carried out in specialised
      centres treating a high number of patients as early as possible in the clinical
      diagnosis. To date, the limited evidence from only 6 randomised trials
      [1,2,3,4,5,6,7], the rarity of the cancer, and the different behaviour/natural
      history depending on the predominant site of origin, (the anal margin, anal canal
      or above the dentate line) provide scanty direction for any individual
      oncologist. Here we aim to provide guidelines which can assist medical, radiation
      and surgical oncologists in the practical management of this unusual cancer. 

PMID- 24947005
TI  - Urgent need for better education: example of maternal dyspnea in a twin
      pregnancy.

PMID- 24947006
TI  - Hierarchically nanotextured surfaces maintaining superhydrophobicity under
      severely adverse conditions.
AB  - Superhydrophobic surfaces are highly desirable for a broad range of technologies
      and products affecting everyday life. Despite significant progress in recent
      years in understanding the principles of hydrophobicity, mostly inspired by
      surface designs found in nature, many man-made surfaces employ readily
      processable materials, ideal to demonstrate principles, but with little chance of
      survivability outside a very limited range of well-controlled environments. Here
      we focus on the rational development of robust, hierarchically nanostructured,
      environmentally friendly, metal-based (aluminum) superhydrophobic surfaces, which
      maintain their performance under severely adverse conditions. Based on their
      functionality, we superpose selected hydrophobic layers (i.e. self-assembled
      monolayers, thin films, or nanofibrous coatings) on hierarchically textured
      aluminum surfaces, collectively imparting high level robustness of
      superhydrophobicity under adverse conditions. These surfaces simultaneously
      exhibit chemical stability, mechanical durability and droplet impalement
      resistance. They impressively maintained their superhydrophobicity after exposure
      to severely adverse chemical environments like strong alkaline (pH ~ 9-10),
      acidic (pH ~ 2-3), and ionic solutions (3.5 weight% of sodium chloride), and
      could simultaneously resist water droplet impalement up to an impact velocity of
      3.2 m s(-1) as well as withstand standard mechanical durability tests. 

PMID- 24947007
TI  - Heterogeneous copper-catalyzed hydroxylation of aryl iodides under air
      conditions.
AB  - In this work, the ligand-free heterogeneous copper Cu-g-C3N4 was synthesized and
      used for the hydroxylation of aryl iodides to synthesize phenols using cheap
      bases. The catalyst was conveniently prepared, air-tolerant, reusable and
      scalable, and is very efficient for a wide range of substrates. The synthesis of
      substituted phenols can be carried out under air conditions and has great
      potential for practical applications. 

PMID- 24947008
TI  - Surface zone articular chondrocytes modulate the bulk and surface mechanical
      properties of the tissue-engineered cartilage.
AB  - The central hypothesis of functional tissue engineering is that an engineered
      construct can serve as a viable replacement tissue in vivo by replicating the
      structure and function of native tissue. In the case of articular cartilage, this
      requires the reproduction of the bulk mechanical and surface lubrication
      properties of native hyaline cartilage. Cartilage tissue engineering has
      primarily focused on achieving the bulk mechanical properties of native cartilage
      such as the compressive aggregate modulus and tensile strength. A scaffold-free
      self-assembling process has been developed that produces engineered cartilage
      with compressive properties approaching native tissue levels. Thus, the next step
      in this process is to begin addressing the friction coefficient and wear
      properties of these engineered constructs. The superficial zone protein (SZP),
      also known as lubricin or PRG4, is a boundary mode lubricant that is synthesized
      by surface zone (SZ) articular chondrocytes. Under conditions of high loading and
      low sliding speeds, SZP reduces friction and wear at the articular surface. The
      objective of this investigation was to determine whether increasing the
      proportion of SZ chondrocytes in cartilage constructs, in the absence of external
      stimuli such as growth factors and mechanical loading, would enhance the
      secretion of SZP and improve their frictional properties. In this study,
      cartilage constructs were engineered through a self-assembling process with
      varying ratios of SZ and middle zone (MZ) chondrocytes (SZ:MZ): 0:100, 25:75,
      50:50, 75:25, and 100:0. Constructs containing different ratios of SZ and MZ
      chondrocytes did not significantly differ in the glycosaminoglycan composition or
      compressive aggregate modulus. In contrast, tensile properties and collagen
      content were enhanced in nearly all constructs containing greater amounts of SZ
      chondrocytes. Increasing the proportion of SZ chondrocytes had the hypothesized
      effect of improving the synthesis and secretion of SZP. However, increasing the
      SZ chondrocyte fraction did not significantly reduce the friction coefficient.
      These results demonstrate that additional factors, such as SZP-binding
      macromolecules, surface roughness, and adhesion, need to be examined to modulate
      the lubrication properties of engineered cartilage. 

PMID- 24947009
TI  - Development of the Pediatric Advanced Care Quality of Life Scale (PAC-QoL):
      evaluating comprehension of items and response options.
AB  - BACKGROUND: Validated tools that measure quality of life (QOL) for children with
      poor prognosis malignancies are not available. We are developing a novel
      instrument, The Pediatric Advanced Care-Quality of Life Scale (PAC-QoL), in order
      to address this gap. Instrument development requires a phase of item reduction
      and assessment of item comprehension in the target population. This manuscript
      provides a report on this phase in the development of the PAC-QoL. PROCEDURE:
      Children with poor prognosis cancer and/or their parents were invited to
      participate in cognitive probing interviews. Participants' understanding of each
      item was rated from 0 (did not understand) to 4 (completely understood). To
      evaluate the response scale, an overall percentage of respondents' ability to
      accurately distinguish between the four response options was calculated. RESULTS:
      Four age- and reporter-specific versions of the PAC-QoL were tested with 74
      participants. Mean (+/-SD) comprehension scores across versions ranged from 3.40
      +/- .0.30 (child self-report) to 3.69 +/- 0.23 (parent of toddler report). The
      number of items deleted or modified to improve understandability ranged from 46%
      of all items on the parent-of-child report to 56% for the child and adolescent
      self-reports. Respondent's abilities to accurately distinguish between response
      scale options ranged from 84% (child-report) to 98% (parent-toddler report).
      CONCLUSIONS: We demonstrate a high degree item understandability and response
      scale separation in the current version of the PAC-QoL. The scale is ready for
      psychometric evaluation in its target population.

PMID- 24947010
TI  - DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced
      apoptosis.
AB  - PD (Parkinson's disease) is a complex disorder that is associated with neuronal
      loss or dysfunction caused by genetic risks, environmental factors and advanced
      aging. It has been reported that DJ-1 mutations rendered neurons sensitive to
      oxidative damage, which led to the onset of familiar PD. However, the molecular
      mechanism is still unclear. In the present study we show that DJ-1 interacts with
      RACK1 (receptor of activated C kinase 1) and increases its dimerization and
      protein stability. The DJ-1 transgene protects cortical neurons from H2O2-induced
      apoptosis, and this protective effect is abrogated by knocking down RACK1.
      Similarly, deletion of DJ-1 in cortical neurons increases the sensitivity to
      H2O2, and the damage can be significantly rescued by DJ-1 or DJ-1/RACK1 co
      transfection, but not by RACK1 alone. We observed further that the interaction of
      DJ-1 and RACK1 is disrupted by H2O2 or MPP+ (1-methyl-4-phenylpyridinium)
      treatment, and the protein levels of DJ-1 and RACK1 decreased in
      neurodegenerative disease models. Taken together, the DJ-1-RACK1 complex protects
      neurons from oxidative stress-induced apoptosis, with the implication that DJ-1
      and RACK1 might be novel targets in the treatment of neurodegenerative diseases. 

PMID- 24947011
TI  - Foam dressing with epidermal growth factor for severe radiation dermatitis in
      head and neck cancer patients.
AB  - This study was conducted to evaluate the effects of foam dressing with human
      recombinant human epidermal growth factor (rhEGF) on the healing process in head
      and neck cancer patients who experience radiation-induced dermatitis (RID). Seven
      patients, including three with oropharyngeal, two with nasopharyngeal and one
      each with hypopharyngeal and laryngeal carcinoma, who underwent radiotherapy (RT)
      for head and neck cancer at the Asan Medical Center from March to December 2008
      were prospectively included in this study. Patients who showed severe RID (more
      than wet desquamation) on the supraclavicular fossa or neck areas were treated by
      wound cleaning and debridement of granulation tissue, followed by daily rhEGF
      spray and foam dressing. Median time to stop exudates and reepithelialisation was
      4 days. Within 14 days (median 8 days), all patients showed complete healing of
      RID and no longer required dressings. This new method of treatment with dressing
      containing rhEGF may have the potential to accelerate the healing process in
      patients with RID. A case-control study is needed to confirm this finding. 

PMID- 24947012
TI  - Transport of rice cyclobutane pyrimidine dimer photolyase into mitochondria
      relies on a targeting sequence located in its C-terminal internal region.
AB  - The cyclobutane pyrimidine dimer (CPD), which represents a major type of DNA
      damage induced by ultraviolet-B (UVB) radiation, is a principal cause of UVB
      induced growth inhibition in plants. CPD photolyase is the primary enzyme for
      repairing CPDs and is crucial for determining the sensitivity of Oryza sativa
      (rice) to UVB radiation. CPD photolyase is widely distributed among species
      ranging from eubacteria to eukaryotes, and is classified into class I or II based
      on its primary structure. We previously demonstrated that rice CPD photolyase
      (OsPHR), which belongs to class II and is encoded by a single-copy gene, is a
      unique nuclear/mitochondrial/chloroplast triple-targeting protein; however, the
      location and nature of the organellar targeting information contained within
      OsPHR are unknown. Here, the nuclear and mitochondrial targeting signal sequences
      of OsPHR were identified by systematic deletion analysis. The nuclear and
      mitochondrial targeting sequences are harbored within residues 487-489 and 391
      401 in the C-terminal region of OsPHR (506 amino acid residues), respectively.
      The mitochondrial targeting signal represents a distinct topogenic sequence that
      differs structurally and functionally from classical N-terminal pre-sequences,
      and this region, in addition to its role in localization to the mitochondria, is
      essential for the proper functioning of the CPD photolyase. Furthermore, the
      mitochondrial targeting sequence, which is characteristic of class-II CPD
      photolyases, was acquired before the divergence of class-II CPD photolyases in
      eukaryotes. These results indicate that rice plants have evolved a CPD photolyase
      that functions in mitochondria to protect cells from the harmful effects of UVB
      radiation. 

PMID- 24947013
TI  - Stronger findings from mass spectral data through multi-peak modeling.
AB  - BACKGROUND: Mass spectrometry-based metabolomic analysis depends upon the
      identification of spectral peaks by their mass and retention time. Statistical
      analysis that follows the identification currently relies on one main peak of
      each compound. However, a compound present in the sample typically produces
      several spectral peaks due to its isotopic properties and the ionization process
      of the mass spectrometer device. In this work, we investigate the extent to which
      these additional peaks can be used to increase the statistical strength of
      differential analysis. RESULTS: We present a Bayesian approach for integrating
      data of multiple detected peaks that come from one compound. We demonstrate the
      approach through a simulated experiment and validate it on ultra performance
      liquid chromatography-mass spectrometry (UPLC-MS) experiments for metabolomics
      and lipidomics. Peaks that are likely to be associated with one compound can be
      clustered by the similarity of their chromatographic shape. Changes of
      concentration between sample groups can be inferred more accurately when multiple
      peaks are available. CONCLUSIONS: When the sample-size is limited, the proposed
      multi-peak approach improves the accuracy at inferring covariate effects. An R
      implementation and data are available at
      http://research.ics.aalto.fi/mi/software/peakANOVA/.

PMID- 24947014
TI  - Preservation of the saphenous vein during laparoendoscopic single-site inguinal
      lymphadenectomy: comparison with the conventional laparoscopic technique.
AB  - OBJECTIVE: To prospectively study the surgical strategies and clinical efficacy
      of laparoendoscopic single-site (LESS) inguinal lymphadenectomy compared with
      conventional endoscopic inguinal lymphadenectomy for the management of inguinal
      nodes. PATIENTS AND METHODS: A total of 12 patients with squamous cell carcinoma
      of the penis who underwent penectomy between February and July 2013 were enrolled
      in the study. All 12 patients underwent bilateral inguinal lymphadenectomy (LESS
      inguinal lymphadenectomy in one limb and conventional endoscopic inguinal
      lymphadenectomy in the other) with preservation of the saphenous vein. All
      lymphatic tissue in the boundaries of the adductor longus muscle (medially), the
      sartorius muscle (laterally), 2 cm above the inguinal ligament (superiorly), the
      Scarpa fascia (superficially) and femoral vessels (deeply) was removed in both
      surgical techniques. All 24 procedures were performed by one experienced surgeon.
      RESULTS: All 24 procedures (12 LESS and 12 conventional endoscopic inguinal
      lymphadenectomies) were completed successfully without conversion to open
      surgery. For LESS inguinal lymphadenectomy and conventional endoscopic inguinal
      lymphadenectomy groups, the mean +/- sd operating time was 94.6 +/- 14.8 min and
      90.8 +/- 10.6 min, respectively (P = 0.145). No significant differences in the
      incidence of postoperative complications (skin-related problems, hecatomb, lower
      extremity oedema, lymphatic complications and overall complications) were noted
      between the two groups (P > 0.05). No lower extremity oedema occurred in any
      limbs of the two groups. No significant differences were observed in either lymph
      node clearance rate or detection rate of histologically positive lymph nodes (P >
      0.05). The patient satisfaction rate with scar appearance and cosmetic results
      was significantly better in the LESS inguinal lymphadenectomy group than in the
      conventional endoscopic inguinal lymphadenectomy group of (75 vs 25%; P = 0.039).
      CONCLUSIONS: This preliminary study suggests that both LESS inguinal
      lymphadenectomy and conventional endoscopic inguinal lymphadenectomy are safe and
      feasible procedures for inguinal lymphadenectomy. Preservation of the saphenous
      vein during LESS inguinal lymphadenectomy/conventional endoscopic inguinal
      lymphadenectomy can effectively reduce the incidence of postoperative lower
      extremity oedema. LESS inguinal lymphadenectomy seems to provide better cosmetic
      results than conventional endoscopic inguinal lymphadenectomy.

PMID- 24947015
TI  - Mean first-passage time for maximal-entropy random walks in complex networks.
AB  - We perform an in-depth study for mean first-passage time (MFPT)--a primary
      quantity for random walks with numerous applications--of maximal-entropy random
      walks (MERW) performed in complex networks. For MERW in a general network, we
      derive an explicit expression of MFPT in terms of the eigenvalues and
      eigenvectors of the adjacency matrix associated with the network. For MERW in
      uncorrelated networks, we also provide a theoretical formula of MFPT at the mean
      field level, based on which we further evaluate the dominant scalings of MFPT to
      different targets for MERW in uncorrelated scale-free networks, and compare the
      results with those corresponding to traditional unbiased random walks (TURW). We
      show that the MFPT to a hub node is much lower for MERW than for TURW. However,
      when the destination is a node with the least degree or a uniformly chosen node,
      the MFPT is higher for MERW than for TURW. Since MFPT to a uniformly chosen node
      measures real efficiency of search in networks, our work provides insight into
      general searching process in complex networks.

PMID- 24947016
TI  - Four-colour FRET reveals directionality in the Hsp90 multicomponent machinery.
AB  - In living organisms, most proteins work in complexes to form multicomponent
      protein machines. The function of such multicomponent machines is usually
      addressed by dividing them into a collection of two state systems at equilibrium.
      Many molecular machines, like Hsp90, work far from equilibrium by utilizing the
      energy of ATP hydrolysis. In these cases, important information is gained from
      the observation of the succession of more than two states in a row. We developed
      a four-colour single-molecule FRET system to observe the succession of states in
      the heat shock protein 90 (Hsp90) system, consisting of an Hsp90 dimer, the
      cochaperone p23 and nucleotides. We show that this multicomponent system is a
      directional ATP-dependent machinery. This reveals a previously undescribed
      mechanism on how cochaperones can modify Hsp90, namely by strengthening of the
      coupling between ATP hydrolysis and a kinetic step involved in the Hsp90 system
      resulting in a stronger directionality. 

PMID- 24947017
TI  - A fast and selective probe for monitoring Pd(2+) in aqueous medium via the dual
      optical readout.
AB  - A ready-to-use coordinative probe has been outlined for the detection of Pd(2+)
      at parts-per-million (ppm) levels which potentially meets real-world-challenges
      through a simple synthetic route, water based-activity, fast response, by-eye
      visualization, regenerative-action, high selectivity and the dual-optical readout
      for precise quantification. 

PMID- 24947018
TI  - The mutational landscape of Hodgkin lymphoma cell lines determined by whole-exome
      sequencing.

PMID- 24947020
TI  - Frequent STAT5B mutations in gammadelta hepatosplenic T-cell lymphomas.

PMID- 24947021
TI  - Birth outcomes of Hispanic women and risks or strengths associated with ethnicity
      and Texas border residence.
AB  - OBJECTIVE: To assess Hispanic ethnicity, border residence, or their interaction
      for association with risk of high gestational weight gain (GWG) and related
      outcomes. DESIGN: Retrospective analysis of 2009 birth data. SETTING: Texas.
      PARTICIPANTS: Participants included 146,458 Hispanic and 104,399 non-Hispanic
      (NH) White women. METHODS: We used adjusted odds ratios (AOR) in logistic
      regression analyses to test the association of Hispanic ethnicity, border
      residence, and their interaction with high GWG, cesarean birth, macrosomia, and
      breastfeeding status at discharge. RESULTS: After adjusting for covariates, risk
      of inadequate or excessive GWG was not associated with being a border resident,
      but Hispanic women compared to NH White women had an increased risk of inadequate
      GWG (AOR = 1.21, 99% confidence interval [CI] [1.17, 1.26]) and decreased risk of
      excessive GWG (AOR = 0.77, 99% CI [0.74, 0.79]). Risk of cesarean birth was
      increased for border residents (AOR = 1.22, 99% CI [1.05, 1.42]), and this risk
      was increased further among border residents who were Hispanic (AOR = 1.52, 99%
      CI [1.30, 1.77]). CONCLUSION: We found strengths and vulnerabilities among
      Hispanic and border-residing women. Hispanic women were at lower risk of
      excessive GWG than NH White women. Border-residing Hispanic women were at greater
      risk of cesarean birth than other women.

PMID- 24947019
TI  - Tumor antigen ROR1 targeted drug delivery mediated selective leukemic but not
      normal B-cell cytotoxicity in chronic lymphocytic leukemia.
AB  - Selective cytotoxicity to cancer cells without compromising their normal
      counterparts pose a huge challenge for traditional drug design. Here we developed
      a tumor antigen-targeted delivery of immunonanoparticle carrying a novel non
      immunosuppressive FTY720 derivative OSU-2S with potent cytotoxicity against
      leukemic B cells. OSU-2S induces activation of protein phosphatase 2A (PP2A),
      phosphorylation and nuclear translocation of SHP1(S591) and deregulation of
      multiple cellular processes in chronic lymphocytic leukemia (CLL) resulting in
      potent cytotoxicity. To preclude OSU-2S-mediated effects on these ubiquitous
      phosphatases in unintended cells and avoid potential adverse effects, we
      developed an OSU-2S-targeted delivery of immunonanoparticles (2A2-OSU-2S-ILP),
      that mediated selective cytotoxicity of CLL but not normal B cells through
      targeting receptor tyrosine kinase ROR1 expressed in leukemic but not normal B
      cells. Developing a novel spontaneous CLL mouse model expressing human ROR1
      (hROR1) in all leukemic B cells, we demonstrate the therapeutic benefit of
      enhanced survival with 2A2-OSU-2S-ILP in vivo. The newly developed non
      immunosuppressive OSU-2S, its delivery using human CLL directed
      immunonanoparticles and the novel transgenic (Tg) mouse model of CLL that
      expresses hROR1 exclusively in leukemic B cell surface are highly innovative and
      can be applied to CLL and other ROR1+ malignancies including mantle cell lymphoma
      and acute lymphoblastic leukemia. 

PMID- 24947022
TI  - Effects of elevated oxygen and carbon dioxide partial pressures on respiratory
      function and cognitive performance.
AB  - Hyperoxia during diving has been suggested to exacerbate hypercapnic narcosis and
      promote unconsciousness. We tested this hypothesis in male volunteers (12 at
      rest, 10 at 75 W cycle ergometer exercise) breathing each of four gases in a
      hyperbaric chamber. Inspired Po2 (PiO2 ) was 0.21 and 1.3 atmospheres (atm)
      without or with an individual subject's maximum tolerable inspired CO2 (PiO2 =
      0.055-0.085 atm). Measurements included end-tidal CO2 partial pressure (PetCO2 ),
      rating of perceived discomfort (RPD), expired minute ventilation (Ve), and
      cognitive function assessed by auditory n-back test. The most prominent finding
      was, irrespective of PetCO2 , that minute ventilation was 8-9 l/min greater for
      rest or exercise with a PiO2 of 1.3 atm compared with 0.21 atm (P < 0.0001). For
      hyperoxic gases, PetCO2 was consistently less than for normoxic gases (P < 0.01).
      For hyperoxic hypercapnic gases, n-back scores were higher than for normoxic
      gases (P < 0.01), and RPD was lower for exercise but not rest (P < 0.02).
      Subjects completed 66 hyperoxic hypercapnic trials without incident, but five
      stopped prematurely because of serious symptoms (tunnel vision, vision loss,
      dizziness, panic, exhaustion, or near syncope) during 69 normoxic hypercapnic
      trials (P = 0.0582). Serious symptoms during hypercapnic trials occurred only
      during normoxia. We conclude serious symptoms with hyperoxic hypercapnia were
      absent because of decreased PetCO2 consequent to increased ventilation. 

PMID- 24947023
TI  - Range of motion, neuromechanical, and architectural adaptations to plantar flexor
      stretch training in humans.
AB  - The neuromuscular adaptations in response to muscle stretch training have not
      been clearly described. In the present study, changes in muscle (at fascicular
      and whole muscle levels) and tendon mechanics, muscle activity, and spinal
      motoneuron excitability were examined during standardized plantar flexor
      stretches after 3 wk of twice daily stretch training (4 * 30 s). No changes were
      observed in a nonexercising control group (n = 9), however stretch training
      elicited a 19.9% increase in dorsiflexion range of motion (ROM) and a 28%
      increase in passive joint moment at end ROM (n = 12). Only a trend toward a
      decrease in passive plantar flexor moment during stretch (-9.9%; P = 0.15) was
      observed, and no changes in electromyographic amplitudes during ROM or at end ROM
      were detected. Decreases in H(max):M(max) (tibial nerve stimulation) were
      observed at plantar flexed (gastrocnemius medialis and soleus) and neutral
      (soleus only) joint angles, but not with the ankle dorsiflexed. Muscle and
      fascicle strain increased (12 vs. 23%) along with a decrease in muscle stiffness
      (-18%) during stretch to a constant target joint angle. Muscle length at end ROM
      increased (13%) without a change in fascicle length, fascicle rotation, tendon
      elongation, or tendon stiffness following training. A lack of change in maximum
      voluntary contraction moment and rate of force development at any joint angle was
      taken to indicate a lack of change in series compliance of the muscle-tendon
      unit. Thus, increases in end ROM were underpinned by increases in maximum
      tolerable passive joint moment (stretch tolerance) and both muscle and fascicle
      elongation rather than changes in volitional muscle activation or motoneuron pool
      excitability.

PMID- 24947025
TI  - A micromechanical model for estimating alveolar wall strain in mechanically
      ventilated edematous lungs.
AB  - To elucidate the micromechanics of pulmonary edema has been a significant medical
      concern, which is beneficial to better guide ventilator settings in clinical
      practice. In this paper, we present an adjoining two-alveoli model to
      quantitatively estimate strain and stress of alveolar walls in mechanically
      ventilated edematous lungs. The model takes into account the geometry of the
      alveolus, the effect of surface tension, the length-tension properties of
      parenchyma tissue, and the change in thickness of the alveolar wall. On the one
      hand, our model supports experimental findings (Perlman CE, Lederer DJ,
      Bhattacharya J. Am J Respir Cell Mol Biol 44: 34-39, 2011) that the presence of a
      liquid-filled alveolus protrudes into the neighboring air-filled alveolus with
      the shared septal strain amounting to a maximum value of 1.374 (corresponding to
      the maximum stress of 5.12 kPa) even at functional residual capacity; on the
      other hand, it further shows that the pattern of alveolar expansion appears
      heterogeneous or homogeneous, strongly depending on differences in air-liquid
      interface tension on alveolar segments. The proposed model is a preliminary step
      toward picturing a global topographical distribution of stress and strain on the
      scale of the lung as a whole to prevent ventilator-induced lung injury. 

PMID- 24947024
TI  - Effects of short-term endurance exercise training on acute doxorubicin-induced
      FoxO transcription in cardiac and skeletal muscle.
AB  - Doxorubicin (DOX) is a potent antitumor agent used in cancer treatment.
      Unfortunately, DOX can induce myopathy in both cardiac and skeletal muscle, which
      limits its clinical use. Importantly, exercise training has been shown to protect
      against DOX-mediated cardiac and skeletal muscle myopathy. However, the
      mechanisms responsible for this exercise-induced muscle protection remain
      elusive. These experiments tested the hypothesis that short-term exercise
      training protects against acute DOX-induced muscle toxicity, in part, due to
      decreased forkhead-box O (FoxO) transcription of atrophy genes. Rats (n = 6 per
      group) were assigned to sedentary or endurance exercise-trained groups and paired
      with either placebo or DOX treatment. Gene expression and protein abundance were
      measured in both cardiac and skeletal muscles to determine the impact of DOX and
      exercise on FoxO gene targets. Our data demonstrate that DOX administration
      amplified FoxO1 and FoxO3 mRNA expression and increased transcription of FoxO
      target genes [i.e., atrogin-1/muscle atrophy F-box (MaFbx), muscle ring finger-1
      (MuRF-1), and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)]
      in heart and soleus muscles. Importantly, exercise training protected against DOX
      induced increases of FoxO1 and MuRF-1 in cardiac muscle and also prevented the
      rise of FoxO3, MuRF-1, and BNIP3 in soleus muscle. Furthermore, our results
      indicate that exercise increased peroxisome proliferator-activated receptor-gamma
      coactivator-1 alpha (PGC-1alpha) in both the heart and soleus muscles. This is
      important because increased PGC-1alpha expression is known to suppress FoxO
      activity resulting in reduced expression of FoxO target genes. Together, these
      results are consistent with the hypothesis that exercise training protects
      against DOX-induced myopathy in both heart (FoxO1 and MuRF-1) and skeletal
      muscles (FoxO3, MuRF-1, and BNIP3). 

PMID- 24947027
TI  - Exercise training and artery function in humans: nonresponse and its relationship
      to cardiovascular risk factors.
AB  - The objectives of our study were to examine 1) the proportion of responders and
      nonresponders to exercise training in terms of vascular function; 2) a priori
      factors related to exercise training-induced changes in conduit artery function,
      and 3) the contribution of traditional cardiovascular risk factors to exercise
      induced changes in artery function. We pooled data from our laboratories
      involving 182 subjects who underwent supervised, large-muscle group, endurance
      type exercise training interventions with pre-/posttraining measures of flow
      mediated dilation (FMD%) to assess artery function. All studies adopted an
      identical FMD protocol (5-min ischemia, distal cuff inflation), contemporary echo
      Doppler methodology, and observer-independent automated analysis. Linear
      regression analysis was used to identify factors contributing to changes in FMD%.
      We found that cardiopulmonary fitness improved, and weight, body mass index
      (BMI), cholesterol, and mean arterial pressure (MAP) decreased after training,
      while FMD% increased in 76% of subjects (P < 0.001). Training-induced increase in
      FMD% was predicted by lower body weight (beta = -0.212), lower baseline FMD%
      (beta = -0.469), lower training frequency (beta = -0.256), and longer training
      duration (beta = 0.367) (combined: P < 0.001, r = 0.63). With the exception of a
      modest correlation with total cholesterol (r = -0.243, P < 0.01), changes in
      traditional cardiovascular risk factors were not significantly related to changes
      in FMD% (P > 0.05). In conclusion, we found that, while some subjects do not
      demonstrate increases following exercise training, improvement in FMD% is present
      in those with lower pretraining body weight and endothelial function. Moreover,
      exercise training-induced change in FMD% did not correlate with changes in
      traditional cardiovascular risk factors, indicating that some cardioprotective
      effects of exercise training are independent of improvement in risk factors. 

PMID- 24947026
TI  - Exercise training decreases activation of the mitochondrial fission protein
      dynamin-related protein-1 in insulin-resistant human skeletal muscle.
AB  - Defects in mitochondrial dynamics, the processes of fission, fusion, and
      mitochondrial autophagy, may contribute to metabolic disease including type 2
      diabetes. Dynamin-related protein-1 (Drp1) is a GTPase protein that plays a
      central role in mitochondrial fission. We hypothesized that aerobic exercise
      training would decrease Drp1 Ser(616) phosphorylation and increase fat oxidation
      and insulin sensitivity in obese (body mass index: 34.6 +/- 0.8 kg/m(2)) insulin
      resistant adults. Seventeen subjects performed supervised exercise for 60
      min/day, 5 days/wk at 80-85% of maximal heart rate for 12 wk. Insulin sensitivity
      was measured by hyperinsulinemic-euglycemic clamp, and fat oxidation was
      determined by indirect calorimetry. Skeletal muscle biopsies were obtained from
      the vastus lateralis muscle before and after the 12-wk program. The exercise
      intervention increased insulin sensitivity 2.1 +/- 0.2-fold (P < 0.01) and fat
      oxidation 1.3 +/- 0.3-fold (P < 0.01). Phosphorylation of Drp1 at Ser(616) was
      decreased (pre vs. post: 0.81 +/- 0.15 vs. 0.58 +/- 0.14 arbitrary units; P <
      0.05) following the intervention. Furthermore, reductions in Drp1 Ser(616)
      phosphorylation were negatively correlated with increases in fat oxidation (r = 
      0.58; P < 0.05) and insulin sensitivity (rho = -0.52; P < 0.05). We also examined
      expression of genes related to mitochondrial dynamics. Dynamin1-like protein
      (DNM1L; P < 0.01), the gene that codes for Drp1, and Optic atrophy 1 (OPA1; P =
      0.05) were significantly upregulated following the intervention, while there was
      a trend towards an increase in expression of both mitofusin protein MFN1 (P =
      0.08) and MFN2 (P = 0.07). These are the first data to suggest that lifestyle
      mediated improvements in substrate metabolism and insulin sensitivity in obese
      insulin-resistant adults may be regulated through decreased activation of the
      mitochondrial fission protein Drp1. 

PMID- 24947028
TI  - Role of VPAC2 receptor in monocrotaline-induced pulmonary hypertension in rats.
AB  - Pulmonary hypertension (PH) is associated with significant morbidity and
      mortality. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase
      activating peptide (PACAP) have pulmonary vasodilatory and positive inotropic
      effects via receptors VPAC1 and VPAC2, which possess a similar affinity for both
      peptides, and PAC1, a PACAP-preferring receptor. VIP is a promising option for PH
      treatment; however, various physiological effects of VIP have limited its
      clinical use. We investigated the effects of VPAC1 and VPAC2 selective agonists
      VIP and PACAP to explore more appropriate means of treatment for PH. We examined
      hemodynamic changes in right ventricular systolic pressure (RVSP), systemic blood
      pressure (SBP), total pulmonary resistance index (TPRI), total systemic
      resistance index, and cardiac index (CI) in response to their agonists with
      monocrotaline (MCT)-induced PH and explored involvement of VIP/PACAP expression
      and receptors in PH. Sprague-Dawley rats were divided into the MCT group
      (administered MCT 60 mg/kg) and control group. In MCT-induced PH, decreased VIP
      and PACAP were associated with upregulation of VPAC1, VPAC2, and PAC1 in lung
      tissues. Intravenous injection of VPAC2-selective agonist BAY 55-9837 and VIP,
      but not [Ala(11,22,28)]VIP, improved the CI. The decrease in SBP with VPAC2
      agonist was significantly less than that in the control. Although they decreased
      SBP, these agonists hardly affected RVSP in the control. Activation of VPAC2
      receptor with BAY 55-9837 effectively improved RVSP, TPRI, and CI in MCT-induced
      PH, suggesting a VPAC2 agonist as a possible promising treatment for PH. 

PMID- 24947029
TI  - Cortisol is not the primary mediator for augmented CXCR4 expression on natural
      killer cells after acute exercise.
AB  - CXC-chemokine receptor 4 (CXCR4) and its ligand, stromal-derived factor 1alpha
      (SDF-1alpha; also known as CXCL12), are crucial for the redistribution of immune
      cells after acute exercise. We investigated the relationships between acute
      exercise and CXCR4 expression on natural killer (NK) cells. Peripheral blood
      mononuclear cells (PBMCs) were cultured with cortisol and analyzed for CXCR4
      expression on CD3(-)/CD56(+) NK cells and NK cell migration activity. To
      determine the effect of exercise, we isolated PBMCs from subjects before and
      after a 90-min exercise at 70% peak O2 uptake (Vo2peak) and determined the
      changes in CXCR4 expression on NK cells after exercise. We cultured PBMCs with
      plasma obtained before and after exercise and with the glucocorticoid antagonist
      RU-486 to determine NK cell migration activity and the effects of cortisol on
      CXCR4 expression in vitro. Cortisol treatment increased CXCR4 expression (P <
      0.05) and migration activity (P < 0.05) of NK cells. Exercise did not affect
      CXCR4 expression on NK cells, whereas incubating them with postexercise plasma
      significantly increased CXCR4 expression (P < 0.05) and migration activity (P <
      0.05). RU-486 blocked cortisol-induced CXCR4 upregulation on NK cells, but only
      partially blocked (7%) CXCR4 upregulation when PMBCs were incubated with
      postexercise plasma. Thus acute exercise increases CXCR4 expression on NK cells
      and their migration activity and may contribute to NK cell redistribution after
      acute exercise; however, cortisol did not appear to be the primary mediator of
      augmented CXCR4 expression. 

PMID- 24947031
TI  - Effects of airway tree asymmetry on the emergence and spatial persistence of
      ventilation defects.
AB  - Asymmetry and heterogeneity in the branching of the human bronchial tree are well
      documented, but their effects on bronchoconstriction and ventilation distribution
      in asthma are unclear. In a series of seminal studies, Venegas et al. have shown
      that bronchoconstriction may lead to self-organized patterns of patchy
      ventilation in a computational model that could explain areas of poor ventilation
      [ventilation defects (VDefs)] observed in positron emission tomography images
      during induced bronchoconstriction. To investigate effects of anatomic asymmetry
      on the emergence of VDefs we used the symmetric tree computational model that
      Venegas and Winkler developed using different trees, including an anatomic human
      airway tree provided by M. Tawhai (University of Auckland), a symmetric tree, and
      three trees with intermediate asymmetry (Venegas JG, Winkler T, Musch G, Vidal
      Melo MF, Layfield D, Tgavalekos N, Fischman AJ, Callahan RJ, Bellani G, Harris
      RS. Nature 434: 777-782, 2005 and Winkler T, Venegas JG. J Appl Physiol 103: 655
      663, 2007). Ventilation patterns, lung resistance (RL), lung elastance (EL), and
      the entropy of the ventilation distribution were compared at different levels of
      airway smooth muscle activation. We found VDefs emerging in both symmetric and
      asymmetric trees, but VDef locations were largely persistent in asymmetric trees,
      and bronchoconstriction reached steady state sooner than in a symmetric tree.
      Interestingly, bronchoconstriction in the asymmetric tree resulted in lower RL
      (~%50) and greater EL (~%25). We found that VDefs were universally caused by
      airway instability, but asymmetry in airway branching led to local triggers for
      the self-organized patchiness in ventilation and resulted in persistent locations
      of VDefs. These findings help to explain the emergence and the persistence in
      location of VDefs found in imaging studies. 

PMID- 24947030
TI  - Skeletal muscle and organ masses differ in overweight adults with type 2
      diabetes.
AB  - Whether lean body mass (LBM) composition, especially skeletal muscle and
      abdominal organs, differs in adults with type 2 diabetes (T2DM) compared with
      nondiabetic healthy controls has not been investigated. A subset of African
      American and Caucasian participants with T2DM from the Look AHEAD (Action for
      Health in Diabetes) trial had body composition assessed and compared with a
      sample of healthy controls. Skeletal muscle mass (SMM), liver, kidneys, and
      spleen mass were quantified using a contiguous slice magnetic resonance imaging
      (MRI) protocol. Cardiac mass was quantified by either a cardiac gated MRI
      protocol or by echocardiography. MRI volumes were converted to mass using assumed
      densities. Dual-energy X-ray absorptiometry assessed LBM. Using general linear
      models adjusted for height, weight, sex, age, race, and interactions of diabetes
      status with race or sex, persons with T2DM (n = 95) had less LBM (49.7 vs. 51.6
      kg) and SMM (24.1 vs. 25.4 kg) and larger kidneys (0.40 vs. 0.36 kg) than
      controls (n = 76) (all P < 0.01). Caucasians with T2DM had larger livers (1.90
      vs. 1.60 kg, P < 0.0001) and spleens (0.29 vs. 0.22 kg, P < 0.01), and T2DM men
      had less cardiac mass than controls (0.25 vs. 0.30 kg, P < 0.001). In this
      sample, T2DM is characterized by less relative skeletal muscle and cardiac mass
      in conjunction with larger kidneys, liver, and spleen. Further investigation is
      needed to establish the causes and metabolic consequences of these race- and sex
      specific organ mass differences in T2DM. 

PMID- 24947032
TI  - Targeted next-generation sequencing on Hirschsprung disease: a pilot study
      exploits DNA pooling.
AB  - To adopt an efficient approach of identifying rare variants possibly related to
      Hirschsprung disease (HSCR), a pilot study was set up to evaluate the performance
      of a newly designed protocol for next generation targeted resquencing. In total,
      20 Chinese HSCR patients and 20 Chinese sex-matched individuals with no HSCR were
      included, for which coding sequences (CDS) of 62 genes known to be in signaling
      pathways relevant to enteric nervous system development were selected for capture
      and sequencing. Blood DNAs from eight pools of five cases or controls were
      enriched by PCR-based RainDance technology (RDT) and then sequenced on a 454 FLX
      platform. As technical validation, five patients from case Pool-3 were also
      independently enriched by RDT, indexed with barcode and sequenced with sufficient
      coverage. Assessment for CDS single nucleotide variants showed DNA pooling
      performed well (specificity/sensitivity at 98.4%/83.7%) at the common variant
      level; but relatively worse (specificity/sensitivity at 65.5%/61.3%) at the rare
      variant level. Further Sanger sequencing only validated five out of 12 rare
      damaging variants likely involved in HSCR. Hence more improvement at variant
      detection and sequencing technology is needed to realize the potential of DNA
      pooling for large-scale resequencing projects. 

PMID- 24947033
TI  - Feasibility study on energy prediction of microwave ablation upon uterine
      adenomyosis and leiomyomas by MRI.
AB  - OBJECTIVE: To evaluate the feasibility of energy prediction of percutaneous
      microwave ablation (PMWA) upon uterine leiomyomas and adenomyosis by MRI.
      METHODS: 63 patients (49 patients with 49 uterine leiomyomas and 14 patients with
      adenomyosis) who underwent ultrasound-guided PMWA treatment were studied during
      the period from June 2011 to December 2012. Before PMWA, contrast-enhanced MRI
      (ceMRI) was performed for all of the patients. Based on the signal intensity (SI)
      of T2 weighted MRI, uterine leiomyomas were classified as hypointense, isointense
      and hyperintense. During ablation, the output energy of the microwave was set at
      50 W, and T11a microwave antennas were used. ceMRI was performed within 7 days
      after PMWA treatment. Non-perfused volume and energy required per unit volume
      were analysed statistically. RESULTS: When unit volume of lesions was ablated,
      uterine adenomyosis needed more energy than did uterine leiomyomas, and
      hyperintense uterine leiomyomas needed more energy than did hypointense pattern.
      CONCLUSIONS: MRI SI of uterine leiomyomas and uterine adenomyosis can be used to
      predict PMWA energy. ADVANCES IN KNOWLEDGE: The conclusions indicate that MRI SI
      can be used to perform pre-treatment planning, which will make the treatment more
      precise.

PMID- 24947035
TI  - Sagging brain masquerading as a pituitary adenoma.

PMID- 24947034
TI  - Effects of preoperative local estrogen in postmenopausal women with prolapse: a
      randomized trial.
AB  - CONTEXT: Pelvic organ prolapse (POP) increases in prevalence with age; recurrence
      after surgical repair is common. OBJECTIVE: The objective of the study was to
      determine the effects of local estrogen treatment on connective tissue synthesis
      and breakdown in the vaginal wall of postmenopausal women planning surgical
      repair of POP. DESIGN: This was a randomized trial. SETTING: The study was
      conducted at an academic tertiary medical center. PATIENTS OR OTHER PARTICIPANTS:
      Postmenopausal women with a uterus and symptomatic anterior and/or apical
      prolapse at stage 2 or greater participated in the study. INTERVENTION: Estrogen
      (Premarin) or placebo cream for 6 weeks preoperatively was the intervention. MAIN
      OUTCOME MEASURES: Full-thickness anterior apical vaginal wall biopsies were
      obtained at the time of hysterectomy and analyzed for mucosa and muscularis
      thickness, connective tissue synthesis, and degradation. Serum levels of estrone
      and 17beta-estradiol were analyzed at baseline and the day of surgery using
      highly sensitive liquid chromatography-tandem mass spectrometry. RESULTS: Fifteen
      women per group (n = 30 total) were randomized; 13 per group underwent surgery.
      Among drug-adherent participants (n = 8 estrogen, n = 13 placebo), epithelial and
      muscularis thickness was increased 1.8- and 2.7-fold (P = .002 and P =.088,
      respectively) by estrogen. Collagen types 1alpha1 and 1alpha2 mRNA increased 6.0-
      and 1.8-fold in the vaginal muscularis (P < .05 for both); collagen type Ia
      protein increased 9-fold in the muscularis (P = .012), whereas collagen III was
      not changed significantly. MMP-12 (human macrophage elastase) mRNA was suppressed
      in the vaginal mucosa from estrogen-treated participants (P = .011), and matrix
      metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the
      muscularis (P = .02). Consistent with menopausal norms, serum estrone and 17beta
      estradiol were low and did not differ among the two groups. CONCLUSIONS: Vaginal
      estrogen application for 6 weeks preoperatively increased synthesis of mature
      collagen, decreased degradative enzyme activity, and increased thickness of the
      vaginal wall, suggesting this intervention improves both the substrate for suture
      placement at the time of surgical repair and maintenance of connective tissue
      integrity of the pelvic floor.

PMID- 24947036
TI  - A newly discovered TSHR variant (L665F) associated with nonautoimmune
      hyperthyroidism in an Austrian family induces constitutive TSHR activation by
      steric repulsion between TM1 and TM7.
AB  - OBJECTIVE: New in vivo mutations in G protein-coupled receptors open
      opportunities for insights into the mechanism of receptor activation. Here we
      describe the molecular mechanism of constitutive TSH receptor (TSHR) activation
      in an Austrian family with three generations of familial nonautoimmune
      hyperthyroidism. PATIENTS: The index patient was diagnosed with hyperthyroidism
      during her first pregnancy. Her first two children were diagnosed with
      hyperthyroidism at the age of 11 and 10 years, respectively. TSH suppression was
      also observed in the third child at the age of 8 years, who has normal free T4
      levels until now. TSH suppression in infancy was observed in the fourth child.
      The mother of the index patient was diagnosed with toxic multinodular goiter at
      the age of 36 years. METHODS: DNA was extracted from blood samples from the index
      patient, her mother, and her four children. Screening for TSHR mutations was
      performed by high-resolution melting assays and subsequent sequencing.
      Elucidation of the underlying mechanism of TSHR activation was carried out by
      generation and structural analysis of TSHR transmembrane homology models and
      verification of model predictions by functional characterization of receptor
      mutations. RESULTS AND CONCLUSIONS: A newly discovered TSHR mutation L665F in
      transmembrane helix 7 of the receptor was detected in six members of this family.
      Functional characterization of L665F revealed constitutive activation for the Gs
      pathway and thus represents the molecular cause for hyperthyroidism in this
      family. The constitutive activation is possibly linked to a steric clash
      introduced by the L665F mutation between transmembrane helices 1 and 7.

PMID- 24947037
TI  - Cardiometabolic phenotyping of patients with familial hypocalcuric hypercalcemia.
AB  - CONTEXT: Heterozygous inactivating mutations of the calcium-sensing receptor
      (CaSR) gene cause alterations in calcium metabolism [familial hypocalciuric
      hypercalcemia (FHH)]. In addition, calcium-sensing receptor is expressed in the
      myocardium and endocrine cells including pancreatic islets, enteroendocrine
      cells, and adipose tissue. OBJECTIVE: To discern whether FHH is associated with
      cardiometabolic alterations of clinical significance, endocrine responses to
      systemic calcium stimulation and oral glucose tolerance tests were performed.
      Ectopic lipid deposition and heart function were assessed using magnetic
      resonance spectroscopy/imaging. PARTICIPANTS: Eight FHH patients and nine
      controls matched for anthropometric characteristics (age 45 +/- 18 y; body mass
      index 29 +/- 4 vs 29 +/- 6 kg/m(2)) were studied to determine cardiac function,
      ectopic and visceral lipid content, and insulin sensitivity and secretion.
      RESULTS: Insulin sensitivity (clamp-like index: 4.5 +/- 0.6 vs 4.3 +/- 0.4 mg/kg
      . min), basal (insulin secretion rate: 266 +/- 33 vs 218 +/- 25 pmol/min), and
      glucose-stimulated beta-cell function (adaptation index: 180.2 +/- 12.2 vs 176.2
      +/- 17.4) as well as calcium-stimulated insulin secretion were comparable between
      FHH and controls, respectively. Ectopic lipid content in liver [3.75% (1.4%; 34%)
      vs 4.18% (0.9%; 28%)], soleus muscle (1.07% +/- 0.38% vs 1.02% +/- 0.56 %), and
      myocardium (0.39% +/- 0.3% vs 0.32% +/- 0.1 %), visceral and sc adipose tissue
      distribution (0.51 +/- 0.16 vs 0.47 +/- 0.17) as well as heart function (ejection
      fraction: 71.5% +/- 8% vs 72.8% +/- 8 %; E to A ratio: 1.4% +/- 0.6% vs 1.3% +/-
      0.7%) were not different between the groups. CONCLUSION: Despite comprehensive
      cardiometabolic phenotyping, no alterations in myocardial function, lipid
      distribution, or glucose metabolism were observed in FHH. Thus, FHH might reflect
      a laboratory finding without any relevant cardiometabolic alterations.

PMID- 24947038
TI  - Promoter hypermethylation of Wnt pathway inhibitors in hepatitis C virus -
      induced multistep hepatocarcinogenesis.
AB  - BACKGROUND: Aberrant DNA methylation profiles are a characteristic feature of
      almost all types of cancers including hepatocellular carcinoma (HCC) and play an
      important role in carcinogenesis. In spite of the accumulating evidence that
      suggests appearance of such aberrations at precancerous stages, very little
      effort has been invested to investigate such possible methylation events in
      patients at risk of developing HCC i.e. those suffering from chronic hepatitis C
      virus (HCV) infection and liver cirrhosis (LC). We reasoned that such an analysis
      could lead to the identification of novel predictive biomarkers as well as
      potential drug targets. METHODS: Promoter methylation status of two Wnt
      inhibitors SFRP2 and DKK1 was quantitatively analyzed by bisulfite pyrosequencing
      in a series of liver biopsy samples. These biopsies were collected from HCV
      infected individuals suffering from chronic hepatitis (CH; n = 15), liver
      cirrhosis (LC; n = 13) and hepatocellular carcinoma (HCC; n = 41). DNA isolated
      from infection free normal livers (N; n =10) was used as control. RESULTS: Our
      analysis revealed that both of the genomic loci were significantly
      hypermethylated in CH patients' livers as compared to normal controls (p = 0.0136
      & 0.0084 for SFRP2 and DKK1, respectively; Mann-Whitney U test). DNA methylation
      levels for both loci were also significantly higher in all the diseased cohorts
      as compared to normal controls (p < 0.0001 and = 0.0011 for SFRP2 and DKK1,
      respectively; Kruskal-Wallis test). However, a comparison between three disease
      cohorts (CH, LC & HCC) revealed no significant difference in levels of DNA
      methylation at DKK1 promoter. In contrast, a progressive increase in DNA
      methylation levels was observed at the SFRP2 promoter (i.e. N < CH & LC < HCC).
      CONCLUSION: This study demonstrated that in HCV infected liver tissues
      hypermethylation at promoter regions of key cancer related genes SFRP2 and DKK1,
      appears early at CH and LC stages, long before the appearance of HCC.

PMID- 24947039
TI  - Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and
      Bim in hepatocellular carcinoma cells.
AB  - The tumor microenvironment, including ischemia, has been increasingly recognized
      as a critical factor in the process of tumor development. Hypoxia and nutrient
      deficiency resulting from ischemia widely exist in solid tumors. Recent studies
      have shown that hypoxia and nutrient deficiency contribute to chemoresistance by
      inducing autophagy, but the underlying mechanism remains unknown. This study
      aimed to explore the role of autophagy induced by low glucose and hypoxia (LH) in
      the chemoresistance of hepatocellular carcinoma cells. Our results demonstrated
      that LH induced autophagy and downregulated Bad and Bim in hepatocellular
      carcinoma cells. The inhibition of autophagy reversed the reduction of these pro
      apoptotic factors during the LH treatment. Furthermore, Bad and Bim were also
      significantly downregulated by autophagy during the process that LH promoted the
      chemoresistance of hepatocellular carcinoma cells. In addition, RNAi or the
      overexpression of Bad and Bim can significantly reduce or increase chemotherapy
      induced cell death, respectively. Taken together, these data indicate that the
      downregulation of Bad and Bim plays a significant role in the autophagy-induced
      chemoresistance of hepatocellular carcinoma cells. 

PMID- 24947040
TI  - Expression of amygdala mineralocorticoid receptor and glucocorticoid receptor in
      the single-prolonged stress rats.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is an anxious disorder
      associated with low levels of corticosterone and enhanced negative feedback of
      the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies showed that the
      amygdala not only has an excitatory effect on the HPA axis but also plays a key
      role in fear-related behaviors. Coticosterone exert actions through binding to
      the mineralocorticoid (MR) and glucocorticoid receptor (GR), which are abundant
      in the amygdala. In our previous study, down-regulation of MR and GR in the
      hippocampus of PTSD rats was found. But the roles of MR and GR in the amygdala of
      PTSD rats is incompletely understood. RESULTS: wistar rats were divided into 1 d,
      7 d, 14 d groups after single prolonged stress (SPS) and control group. SPS is a
      reliable animal model of PTSD. Open field test (OF) and elevated plus maze tests
      (EPM) were performed to examine fear-related behaviors. Morphological changes of
      the ultrastructure of the amygdala neurons were assessed by transmission electron
      microscopy (TEM). Dual-immunofluorescence histochemistry was used to determined
      subcellular distribution and colocalization of MR- and GR-ir. Protein and mRNA of
      MR and GR was examined by western blotting and RT-PCR. OF and EPM showed enhanced
      fear in SPS rats. Abnormal neuronal morphology was discovered in the amygdala of
      SPS rats. The expression of MR- and GR-ir intensity, mRNA and protein within the
      amygdala decreased after SPS at 1 day, and then gradually recovered by 14 days,
      although the degree of decrease and recovery were different amongst techniques.
      We found no change in the MR/GR ratio at 3 levels of the amygdala. But more
      cytoplasmic distribution and decreased colocalization of MR- and GR-ir were
      observed in the amygdala after 7 days of SPS. CONCLUSION: These data suggest that
      change of MR and GR in the amygdala are involved in the mechanisms of fear in
      PTSD.

PMID- 24947041
TI  - IL4 receptor ILR4alpha regulates metastatic colonization by mammary tumors
      through multiple signaling pathways.
AB  - IL4, a cytokine produced mainly by immune cells, may promote the growth of
      epithelial tumors by mediating increased proliferation and survival. Here, we
      show that the type II IL4 receptor (IL4R) is expressed and activated in human
      breast cancer and mouse models of breast cancer. In metastatic mouse breast
      cancer cells, RNAi-mediated silencing of IL4Ralpha, a component of the IL4R, was
      sufficient to attenuate growth at metastatic sites. Similar results were obtained
      with control tumor cells in IL4-deficient mice. Decreased metastatic capacity of
      IL4Ralpha "knockdown" cells was attributed, in part, to reductions in
      proliferation and survival of breast cancer cells. In addition, we observed an
      overall increase in immune infiltrates within IL4Ralpha knockdown tumors,
      indicating that enhanced clearance of knockdown tumor cells could also contribute
      to the reduction in knockdown tumor size. Pharmacologic investigations suggested
      that IL4-induced cancer cell colonization was mediated, in part, by activation of
      Erk1/2, Akt, and mTOR. Reduced levels of pAkt and pErk1/2 in IL4Ralpha knockdown
      tumor metastases were associated with limited outgrowth, supporting roles for Akt
      and Erk activation in mediating the tumor-promoting effects of IL4Ralpha.
      Collectively, our results offer a preclinical proof-of-concept for targeting
      IL4/IL4Ralpha signaling as a therapeutic strategy to limit breast cancer
      metastasis.

PMID- 24947042
TI  - Microbiota modulate tumoral immune surveillance in lung through a gammadeltaT17
      immune cell-dependent mechanism.
AB  - Commensal bacteria are crucial to maintain immune homeostasis in mucosal tissues
      and disturbances in their ecology can affect disease susceptibility. Here, we
      report evidence that commensal bacteria shape the efficiency of immune
      surveillance in mucosal tissues. Antibiotic-treated (Abt) mice were more
      susceptible to development of engrafted B16/F10 melanoma and Lewis lung
      carcinoma, exhibiting a shortened mean survival time with more numerous and
      larger tumor foci in the lungs. The defective antitumor response of Abt mice was
      independent of dehydration caused by antibiotics. Host defenses relied upon
      intact commensal bacteria with no class specificity. Mechanistic investigations
      revealed a defective induction of the gammadeltaT17 cell response in lungs of Abt
      mice; here, more aggressive tumor development was observed, possibly related to a
      reduction in IL6 and IL23 expression there. Adding normal gammadeltaT cells or
      supplementing IL17 restored the impaired immune surveillance phenotype in Abt
      mice. Overall, our results demonstrated the importance of commensal bacteria in
      supporting the host immune response against cancer, defined an important role for
      gammadeltaT17 responses in the mechanism, and suggested deleterious effects of
      antibiotic treatment on cancer susceptibility and progression.

PMID- 24947044
TI  - Further studies into the photodissociation pathways of 2-bromo-2-nitropropane and
      the dissociation channels of the 2-nitro-2-propyl radical intermediate.
AB  - These experiments investigate the decomposition mechanisms of geminal dinitro
      energetic materials by photolytically generating two key intermediates: 2
      nitropropene and 2-nitro-2-propyl radicals. To characterize the unimolecular
      dissociation of each intermediate, we form them under collision-free conditions
      using the photodissociation of 2-bromo-2-nitropropane; the intermediates are
      formed at high internal energies and undergo a multitude of subsequent
      unimolecular dissociation events investigated herein. Complementing our prior
      work on this system, the new data obtained with a crossed-laser molecular beam
      scattering apparatus with VUV photoionization detection at Taiwan's National
      Synchrotron Radiation Research Center (NSRRC) and new velocity map imaging data
      better characterize two of the four primary 193 nm photodissociation channels.
      The C-Br photofission channel forming the 2-nitro-2-propyl radicals has a
      trimodal recoil kinetic energy distribution, P(ET), suggesting that the 2-nitro-2
      propyl radicals are formed both in the ground electronic state and in two low
      lying excited electronic states. The new data also revise the HBr
      photoelimination P(ET) forming the 2-nitropropene intermediate. We then resolved
      the multiple competing unimolecular dissociation channels of each photoproduct,
      confirming many of the channels detected in the prior study, but not all. The new
      data detected HONO product at m/e = 47 using 11.3 eV photoionization from both
      intermediates; analysis of the momentum-matched products allows us to establish
      that both 2-nitro-2-propyl -> HONO + CH3CCH2 and 2-nitropropene -> HONO + C3H4
      occur. Photoionization at 9.5 eV allowed us to detect the mass 71 coproduct
      formed in OH loss from 2-nitro-2-propyl; a channel missed in our prior study. The
      dynamics of the highly exothermic 2-nitro-2-propyl -> NO + acetone dissociation
      is also better characterized; it evidences a sideways scattered angular
      distribution. The detection of some stable 2-nitropropene photoproducts allows us
      to fit signal previously assigned to H loss from 2-nitro-2-propyl radicals.
      Overall, the data provide a comprehensive study of the unimolecular dissociation
      channels of these important nitro-containing intermediates. 

PMID- 24947043
TI  - Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell
      division in glioblastoma.
AB  - Cancer stem cells, capable of self-renewal and multipotent differentiation,
      influence tumor behavior through a complex balance of symmetric and asymmetric
      cell divisions. Mechanisms regulating the dynamics of stem cells and their
      progeny in human cancer are poorly understood. In Drosophila, mutation of brain
      tumor (brat) leads to loss of normal asymmetric cell division by developing
      neural cells and results in a massively enlarged brain composed of neuroblasts
      with neoplastic properties. Brat promotes asymmetric cell division and directs
      neural differentiation at least partially through its suppression on Myc. We
      identified TRIM3 (11p15.5) as a human ortholog of Drosophila brat and demonstrate
      its regulation of asymmetric cell division and stem cell properties of
      glioblastoma (GBM), a highly malignant human brain tumor. TRIM3 gene expression
      is markedly reduced in human GBM samples, neurosphere cultures, and cell lines
      and its reconstitution impairs growth properties in vitro and in vivo. TRIM3
      expression attenuates stem-like qualities of primary GBM cultures, including
      neurosphere formation and the expression of stem cell markers CD133, Nestin, and
      Nanog. In GBM stem cells, TRIM3 expression leads to a greater percentage dividing
      asymmetrically rather than symmetrically. As with Brat in Drosophila, TRIM3
      suppresses c-Myc expression and activity in human glioma cell lines. We also
      demonstrate a strong regulation of Musashi-Notch signaling by TRIM3 in GBM
      neurospheres and neural stem cells that may better explain its effect on stem
      cell dynamics. We conclude that TRIM3 acts as a tumor suppressor in GBM by
      restoring asymmetric cell division.

PMID- 24947045
TI  - Implementation and evaluation of the 5As framework of obesity management in
      primary care: design of the 5As Team (5AsT) randomized control trial.
AB  - BACKGROUND: Obesity is a pressing public health concern, which frequently
      presents in primary care. With the explosive obesity epidemic, there is an urgent
      need to maximize effective management in primary care. The 5As of Obesity
      ManagementTM (5As) are a collection of knowledge tools developed by the Canadian
      Obesity Network. Low rates of obesity management visits in primary care suggest
      provider behaviour may be an important variable. The goal of the present study is
      to increase frequency and quality of obesity management in primary care using the
      5As Team (5AsT) intervention to change provider behaviour. METHODS/DESIGN: The
      5AsT trial is a theoretically informed, pragmatic randomized controlled trial
      with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP,
      mental health, dietitians) will be randomized to control or the 5AsT intervention
      group, to participate in biweekly learning collaborative sessions supported by
      internal and external practice facilitation. The learning collaborative content
      addresses provider-identified barriers to effective obesity management in primary
      care. Evidence-based shared decision making tools will be co-developed and
      iteratively tested by practitioners. Evaluation will be informed by the RE-AIM
      framework. The primary outcome measure, to which participants are blinded, is
      number of weight management visits/full-time equivalent (FTE) position. Patient
      level outcomes will also be assessed, through a longitudinal cohort study of
      patients from randomized practices. Patient outcomes include clinical (e.g., body
      mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D),
      and satisfaction with care. Qualitative data collected from providers and
      patients will be evaluated using thematic analysis to understand the context,
      implementation and effectiveness of the 5AsT program. DISCUSSION: The 5AsT trial
      will provide a wide range of insights into current practices, knowledge gaps and
      barriers that limit obesity management in primary practice. The use of existing
      resources, collaborative design, practice facilitation, and integrated feedback
      loops cultivate an applicable, adaptable and sustainable approach to increasing
      the quantity and quality of weight management visits in primary care. TRIAL
      REGISTRATION: NCT01967797.

PMID- 24947046
TI  - Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly
      over-expressed in mycosis fungoides and correlates with poor prognosis.
AB  - Mycosis fungoides (MF) often mimics the common chronic inflammatory skin diseases
      and is difficult to be diagnosed with certainty, partly because of the lack of
      well-characterized molecular markers. Previously, we discovered that TOX, a key T
      cell development regulator,was aberrantly over-expressed in early stage MF. In
      the current multi-center study involving two independent patient cohorts, we
      determined the prevalence of TOX over-expression in the full spectrum of MF skin
      biopsies, and tested if TOX expression levels correlated with long term clinical
      outcomes. We examined TOX expression levels in 113 MF biopsies. We found that the
      MF biopsies expressed higher TOX mRNA than the controls in both cohorts (17.9
      fold in cohort 1, P = 0.002; 5.8 fold in cohort 2, P < 0.0001). In addition,
      thicker skin lesions such as plaques and tumors expressed even higher TOX levels
      than thinner patches. Further, TOX over-expression differentiated MF from the
      controls (area under the curve [AUC]=0.87, P < 0.0001). Finally, high TOX mRNA
      levels correlated with increased risks of disease progression (P = 0.003) and
      disease-specific mortality (P = 0.008). In conclusion, TOX may be a useful marker
      for improving MF diagnosis and prognostication. 

PMID- 24947047
TI  - Serum B7-H4 expression is a significant prognostic indicator for patients with
      gastric cancer.
AB  - BACKGROUND: B7-H4 is a novel B7 ligand that plays an important role in the T cell
      mediated immune response as a negative regulator. Previous studies have suggested
      the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study
      is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in
      circulation and to investigate the correlations between sB7-H4 levels and
      clinicopathological parameters as well as the survival rate of patients with
      gastric cancer. METHODS: Blood specimens from 132 patients with gastric cancer
      and 63 healthy volunteers were analyzed by sandwich enzyme-linked immunosorbent
      assay. RESULTS: Median concentrations of sB7-H4 in patients with gastric cancer
      were significantly higher than those in healthy volunteers (16.85 versus 10.46
      ng/mL; P = 0.008). Median levels of sB7-H4 were significantly correlated with
      tumor size, lymph node metastasis, the depth of tumor invasion and tumor-node
      metastasis classification (P = 0.002, P = 0.001, P = 0.041 and P <0.001,
      respectively), but not with sex, age, tumor location or histological subtype (all
      P >0.05). Additionally, the overall survival rate was significantly lower in
      patients with high sB7-H4 levels when compared with low sB7-H4 levels (50.0%
      versus 77.3%, chi2 = 10.78, P = 0.001). Moreover, multivariate analysis
      demonstrated that the risk of death was significantly higher in patients with
      high sB7-H4 levels than in those with low sB7-H4 levels (P = 0.039). CONCLUSIONS:
      sB7-H4 is a valuable blood marker for predicting the progression and prognosis of
      patients with gastric cancer.

PMID- 24947048
TI  - Single cell mutational analysis of PIK3CA in circulating tumor cells and
      metastases in breast cancer reveals heterogeneity, discordance, and mutation
      persistence in cultured disseminated tumor cells from bone marrow.
AB  - BACKGROUND: Therapeutic decisions in cancer are generally guided by molecular
      biomarkers or, for some newer therapeutics, primary tumor genotype. However,
      because biomarkers or genotypes may change as new metastases emerge, circulating
      tumor cells (CTCs) from blood are being investigated for a role in guiding real
      time drug selection during disease progression, expecting that CTCs will
      comprehensively represent the full spectrum of genomic changes in metastases.
      However, information is limited regarding mutational heterogeneity among CTCs and
      metastases in breast cancer as discerned by single cell analysis. The presence of
      disseminated tumor cells (DTCs) in bone marrow also carry prognostic significance
      in breast cancer, but with variability between CTC and DTC detection. Here we
      analyze a series of single tumor cells, CTCs, and DTCs for PIK3CA mutations and
      report CTC and corresponding metastatic genotypes. METHODS: We used the
      MagSweeper, an immunomagnetic separation device, to capture live single tumor
      cells from breast cancer patients' primary and metastatic tissues, blood, and
      bone marrow. Single cells were screened for mutations in exons 9 and 20 of the
      PIK3CA gene. Captured DTCs grown in cell culture were also sequenced for PIK3CA
      mutations. RESULTS: Among 242 individual tumor cells isolated from 17 patients
      and tested for mutations, 48 mutated tumor cells were identified in three
      patients. Single cell analyses revealed mutational heterogeneity among CTCs and
      tumor cells in tissues. In a patient followed serially, there was mutational
      discordance between CTCs, DTCs, and metastases, and among CTCs isolated at
      different time points. DTCs from this patient propagated in vitro contained a
      PIK3CA mutation, which was maintained despite morphological changes during 21
      days of cell culture. CONCLUSIONS: Single cell analysis of CTCs can demonstrate
      genotypic heterogeneity, changes over time, and discordance from DTCs and distant
      metastases. We present a cautionary case showing that CTCs from any single blood
      draw do not always reflect metastatic genotype, and that CTC and DTC analyses may
      provide independent clinical information. Isolated DTCs remain viable and can be
      propagated in culture while maintaining their original mutational status,
      potentially serving as a future resource for investigating new drug therapies.

PMID- 24947050
TI  - An unusual timing for symptomatic chest pain in an adult chest wall myofibroma: a
      case report.
AB  - INTRODUCTION: Myofibromas are benign mesenchymal neoplasms that can present as
      solitary and multicentric lesions. They can occur in several locations and can
      occur at any age from neonates to elderly patients. However, most of the lesions
      are found in neonates and babies. It rarely occurs in adults. CASE PRESENTATION:
      A 29-year-old Taiwanese man presented with persistent dull chest pain in his
      right lateral chest wall for 2 weeks. A chest X-ray showed a faint patchy opacity
      over the periphery of his right upper lung zone. Computed tomography and magnetic
      resonance imaging showed a lobulated mass at the intercostal space between his
      right fifth and sixth ribs with contrast enhancement and bone invasion.
      Malignancy could not be excluded. A percutaneous needle aspiration biopsy failed
      due to technique issues, so he underwent a thoracotomy and the tumor was excised
      with Marlex mesh repairs for the thoracic defect. Pathology confirmed a
      myofibroma without malignancy. He recovered uneventfully and no local recurrence
      was detected at the 1-year follow-up examination. CONCLUSIONS: Chest wall
      myofibroma presenting with chest pain has never been reported in adults. It is a
      challenge to differentiate myofibroma from malignancy in chest wall
      preoperatively, such as seen in our patient. To the best of our knowledge, this
      has not been previously reported in the scientific literature. Although
      myofibroma rarely occurs in the chest wall and adults, it must be suspected in
      any chest wall tumor presenting with chest pain.

PMID- 24947049
TI  - Long-term treatment with a beta-blocker timolol attenuates renal-damage in
      diabetic rats via enhancing kidney antioxidant-defense system.
AB  - The factors with increasing diabetes-prevalence lead to significant global
      increases in chronic kidney disease. Since hyperglycemia generates more ROS and
      attenuates cellular antioxidant-defense mechanisms, numerous studies demonstrated
      that hyperglycemia-induced oxidative stress played a major role in the
      extracellular matrix expansion in tissues. Although no direct relation between
      activation of beta-adrenergic (beta-AR) system and kidney disease in diabetes and
      since beta-blockers demonstrate marked beneficial effects due to their scavenging
      free radicals and/or acting as an antioxidant in diabetic animal studies, the
      eventual objective of the present study was to determine whether timolol
      treatment of streptozotocin-induced diabetic rats (5 mg/kg, daily following
      diabetes-induction, for 12-week) has advantage to prevent hyperglycemia-induced
      renal-damage via enhancing the depressed antioxidant defense in the kidney. Light
      microscopy data and their quantification demonstrated that timolol-treatment
      prevented basically glomerular hypertrophy, expansion in mesangium cell size,
      thickening and fibrosis in glomerular basement membrane, and accumulation of
      glycogen into tubular epithelial cells. Additionally, electron microscopy data
      demonstrated that timolol-treatment could also prevent diabetes-induced changes
      in the kidney tissue such as hypertrophy in podocytes, lost of filtration gaps
      and slit-diaphragms, and vacuolization in the distal tubular cells. Biochemical
      analysis basically on enzymes of antioxidant-defense system, including
      glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate
      dehydrogenase, further supported that diabetes-induced damage in the kidney is
      mostly dependent on the increased oxidative stress and timolol, having an
      antioxidant-like action, could protect the kidney against hyperglycemia-induced
      damage without normalization of high-blood glucose level. Consequently, it can be
      suggested that although beta-blockers are widely used for the treatment of
      cardiovascular diseases, beta-blocker therapy of diabetics seems to be a new
      therapeutic approach against hyperglycemia-induced kidney damage in diabetic
      patients. 

PMID- 24947051
TI  - Faculty development to enhance humanistic teaching and role modeling: a
      collaborative study at eight institutions.
AB  - BACKGROUND: There is increased emphasis on practicing humanism in medicine but
      explicit methods for faculty development in humanism are rare. OBJECTIVE: We
      sought to demonstrate improved faculty teaching and role modeling of humanistic
      and professional values by participants in a multi-institutional faculty
      development program as rated by their learners in clinical settings compared to
      contemporaneous controls. DESIGN: Blinded learners in clinical settings rated
      their clinical teachers, either participants or controls, on the previously
      validated 10-item Humanistic Teaching Practices Effectiveness (HTPE)
      questionnaire. PARTICIPANTS: Groups of 7-9 participants at 8 academic medical
      centers completed an 18-month faculty development program. Participating faculty
      were chosen by program facilitators at each institution on the basis of being
      promising teachers, willing to participate in the longitudinal faculty
      development program. INTERVENTION: Our 18-month curriculum combined experiential
      learning of teaching skills with critical reflection using appreciative inquiry
      narratives about their experiences as teachers and other reflective discussions.
      MAIN MEASURES: The main outcome was the aggregate score of the ten items on the
      questionnaire at all institutions. KEY RESULTS: The aggregate score favored
      participants over controls (P = 0.019) independently of gender, experience on
      faculty, specialty area, and/or overall teaching skills. CONCLUSIONS:
      Longitudinal, intensive faculty development that employs experiential learning
      and critical reflection likely enhances humanistic teaching and role modeling.
      Almost all participants completed the program. Results are generalizable to other
      schools.

PMID- 24947052
TI  - A review of primary osteosarcoma of the larynx and case report.
AB  - Sarcomas of the larynx are exceedingly uncommon, of which primary laryngeal
      osteosarcomas are the rarest. To date, 25 cases of primary laryngeal
      osteosarcomas have been reported in the literature. Laryngeal osteosarcomas may
      closely simulate sarcomatoid carcinomas, since both entities share clinical,
      histological and immunohistochemical features. Herein, we report a case of
      primary laryngeal osteosarcoma in a 55 year old male, focusing on the importance
      of light microscopic, immunohistochemical and ultrastructural features in
      accurately establishing the diagnosis. In addition, the current paper provides a
      review of the English language literature on the subject. Laryngeal osteosarcomas
      usually carry a dismal prognosis with no general consensus on the most effective
      mode of therapy. Similarly, the current patient developed bilateral lung
      metastases 8 months after the initial surgery.

PMID- 24947054
TI  - On the number of factors to retain in exploratory factor analysis for ordered
      categorical data.
AB  - Conducting exploratory factor analysis (EFA) using statistical extraction methods
      has been recommended, but little is known about the accuracy of the decisions
      regarding the number of factors to retain for ordered categorical item data by
      considering a chi-square test, fit indices, and conventional criteria, such as
      eigenvalue >1 and parallel analysis. With computer-generated data, the authors
      examined the accuracy of decisions regarding the number of factors to retain for
      categorical item data, by combining these pieces of information using weighted
      least-square with mean and variance adjustment estimation methods based on
      polychoric correlations. A chi-square difference test was also conducted to
      compare nested EFA models. The results showed that the eigenvalue >1 criterion
      resulted in too many factors, in general. The chi-square test, chi-square
      difference test, fit indices, and parallel analysis performed reasonably well
      when the number of scale points was four, the number of items was 24, the sample
      size was at least 200, and the categorical distributions were similar across
      items. However, parallel analysis had a tendency toward factor underextraction
      when the correlation among factors was .50, particularly for two-point and 12
      item scales. 

PMID- 24947053
TI  - Verrucous carcinoma with dysplasia or minimal invasion: a variant of verrucous
      carcinoma with extremely favorable prognosis.
AB  - Verrucous carcinomas (VC) recur locally but do not metastasize in the absence of
      an invasive squamous cell carcinoma (SCC) component. Although excluded from the
      definition of pure VC, some tumors harbor only dysplasia or minimal invasion,
      findings of unknown clinical significance. Surgically resected VC cases from two
      institutions were collected and categorized into three types: VC, VC with
      dysplasia or minimal invasion (VCDMI), defined as SCC less than or equal to 2 mm
      in depth, and SCC arising in VC (SCC-VC) where the SCC was greater than 2 mm in
      depth. Cases were also matched with conventional SCC based on location and T and
      N-stages, and clinical follow up was obtained. Of the 58 total cases, 18 were VC,
      26 VCDMI, and 14 SCC-VC. Only 1 of 18 (5.6 %) VC and 5 of 26 (19.2 %) VCDMI cases
      recurred locally (p = 0.37) versus 7 of 14 (50 %) SCC-VC (p = 0.01). All VC and
      VCDMI cases were node negative at presentation whereas SCC-VC had nodal
      metastases in 2 of 14 (14.3 %) cases. No patients with VC or VCDMI died from
      disease, whereas 5 of 14 (35.7 %) patients with SCC-VC died from disease. T-stage
      matched conventional SCC cases from institutional databases had worse outcomes
      than VC and VCDMI, but not after they were matched for both T and N-stages. Our
      findings suggest that dysplasia and/or minimal invasive SCC do not adversely
      affect outcomes in tumors otherwise showing diagnostic features of VC.

PMID- 24947055
TI  - The individual and combined effect of colorectal cancer and diabetes on health
      related quality of life and sexual functioning: results from the PROFILES
      registry.
AB  - PURPOSE: This study examined the individual and combined effect of having
      colorectal cancer (CRC) and diabetes mellitus (DM) on health-related quality of
      life (HRQoL) and sexual functioning. METHODS: Data from questionnaires collected
      in 2010 among CRC patients and a sample of the general Dutch population were
      used. All persons older than 60 years were included in this study. DM prevalence
      among the CRC sample as well as the sample of the general population was self
      reported. HRQoL was measured using the European Organization for Research and
      Treatment of Cancer (EORTC) Quality of Life Questionnaire version 3.0 (QLQ-C30),
      and sexual functioning was assessed with four scales from the EORTC-QLQ-CR38.
      RESULTS: In total 624 persons without CRC and DM, 78 persons with DM only, 1,731
      with CRC only, and 328 with both CRC and DM were included. Having both CRC and DM
      did not result in lower HRQoL and sexual functioning than the sum of the
      individual effects of both diseases. CRC, irrespective of having DM, was
      associated with lower scores on most EORTC-QLQ-C30 subscales, except global
      health, pain, and appetite loss. CRC was also independently associated with more
      erection problems among males. DM, irrespective of having CRC, was associated
      with lower physical functioning and more symptoms of dyspnea. CONCLUSIONS: Having
      both CRC and DM did not result in lower HRQoL and sexual functioning than the sum
      of the individual effects of both diseases. As CRC was found to be consistently
      associated with lower functioning and more symptoms, CRC and its treatment seem
      to contribute stronger to lower HRQoL and sexual functioning compared with DM.

PMID- 24947056
TI  - Comparison of a novel, simple nutrition screening tool for adult oncology
      inpatients and the Malnutrition Screening Tool (MST) against the Patient
      Generated Subjective Global Assessment (PG-SGA).
AB  - BACKGROUND: Oncology inpatients are at high risk of malnutrition. Identification
      of at risk patients by nutrition screening requires a practical and easy to use
      tool. In this study, we have compared a simple, novel nutrition screening tool
      designed for an oncology inpatient setting and the Malnutrition Screening Tool
      (MST) against the Patient-Generated Subjective Global Assessment (PG-SGA).
      METHODS: This was an observational study to compare assessment of nutritional
      status by PG-SGA with nutrition screening using the Royal Marsden Nutrition
      Screening Tool (RMNST) and the MST. Patients were recruited from a single
      tertiary cancer centre. RESULTS: One hundred and twenty-six oncology inpatients
      underwent a full nutritional assessment and nutrition screening. The PG-SGA tool
      identified 90 (71%) patients as malnourished or at risk and 36 (29%) patients as
      well-nourished. The RMNST had a sensitivity of 93% and a specificity of 53%, and
      the MST had a sensitivity of 66% and a specificity of 83 %. Predictive value (ROC
      AUC) of both screening tools was excellent at 0.84 and 0.83 for RMNST and MST,
      respectively. CONCLUSIONS: This study identified a high prevalence of
      malnutrition in the population with 71% of patients being identified as
      malnourished or at risk of malnutrition. The RMNST had an excellent sensitivity
      for identifying patients who were malnourished or at risk of malnutrition in the
      inpatient setting although it had a poor specificity. The MST had a poorer
      sensitivity of 66 %. We would recommend that the RMNST is trialled in other
      oncology inpatient settings and also in the outpatient setting.

PMID- 24947057
TI  - Concentrated citrate locking in order to reduce the long-term complications of
      central venous catheters: a randomized controlled trial in patients with
      hematological malignancies.
AB  - PURPOSE AND METHODS: Central venous catheter (CVC)-related thrombosis and
      infections are frequently occurring complications in patients with hematological
      malignancies. At present, heparin is most often used as a locking solution.
      Trisodium citrate (TSC) had been shown to be a very effective antimicrobial
      catheter locking in hemodialysis patients. We performed a prospective randomized
      phase III multicenter trial to determine the efficacy of TSC as a locking
      solution compared to heparin in preventing CVC-related thrombosis and infections
      in patients with hematological malignancies. RESULTS: Thirty-four episodes of CVC
      related bloodstream infections (CVC-BSI) occurred in the 108 patients who were
      randomized to locking with heparin compared with 35 episodes in the 99 patients
      who were randomized to locking with TSC (P = 0.654). We did find seven times more
      CVC-BSI with gram-negative rods in CVCs locked with heparin (P = 0.041). The
      cumulative incidence of symptomatic thrombosis was 10% in the heparin group and
      5% in the TSC group (hazard ratio 0.525; 95% confidence interval 0.182-1.512).
      CONCLUSION: This study shows that locking with TSC in patients with hematological
      malignancies significantly reduced the incidence of CVC-BSI with gram-negative
      rods. However, the incidence of CVC-BSI with coagulase-negative staphylococcus or
      CVC-related thrombosis was not reduced by TSC locking.

PMID- 24947058
TI  - Gastric vs Small Bowel Feeding in Critically Ill Neurologically Injured Patients:
      Results of a Multicenter Observational Study.
AB  - BACKGROUND: To evaluate gastric compared with small bowel feeding on nutrition
      and clinical outcomes in critically ill, neurologically injured patients.
      MATERIALS AND METHODS: International, prospective observational studies involving
      353 intensive care units (ICUs) were included. Eligible patients were critically
      ill, mechanically ventilated with neurological diagnoses who remained in the ICU
      and received enteral nutrition (EN) exclusively for at least 3 days. Sites
      provided data, including patient characteristics, nutrition practices, and 60-day
      outcomes. Patients receiving gastric or small bowel feeding were compared.
      Covariates including age, sex, body mass index, and Acute Physiology and Chronic
      Health Evaluation II score were used in the adjusted analyses. RESULTS: Of the
      1691 patients who met our inclusion criteria, 1407 (94.1%) received gastric
      feeding and 88 (5.9%) received small bowel feeding. Adequacy of calories from EN
      was highest in the gastric group (60.2% and 52.3%, respectively, unadjusted
      analysis; P = .001), but this was not significant in the adjusted model (P =
      .428). The likelihood of EN interruptions due to gastrointestinal (GI)
      complications was higher for the gastric group (19.6% vs 4.7%, unadjusted model;
      P = .015). There were no significant differences in the rate of discontinuation
      of mechanical ventilation (hazard ratio [HR], 0.86; 95% confidence interval [CI],
      0.66-1.12; P = .270) or the rate of being discharged alive from the ICU (HR,
      0.94; 95% CI, 0.72-1.23; P = .641) and hospital (HR, 1.16; 95% CI, 0.87-1.55; P =
      .307) after adjusting for confounders. CONCLUSIONS: Despite a higher likelihood
      of EN interruptions due to GI complications, gastric feeding may be associated
      with better nutrition adequacy, but neither route is associated with better
      clinical outcomes.

PMID- 24947059
TI  - Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)
      interreader reliability, accuracy, and survival outcomes.
AB  - There has been no established qualitative system of interpretation for therapy
      response assessment using PET/CT for head and neck cancers. The objective of this
      study was to validate the Hopkins interpretation system to assess therapy
      response and survival outcome in head and neck squamous cell cancer patients
      (HNSCC). METHODS: The study included 214 biopsy-proven HNSCC patients who
      underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of
      treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3
      nuclear medicine physicians, independently. The studies were scored using a
      qualitative 5-point scale, for the primary tumor, for the right and left neck,
      and for overall assessment. Scores 1, 2, and 3 were considered negative for
      tumors, and scores 4 and 5 were considered positive for tumors. The Cohen kappa
      coefficient (kappa) was calculated to measure interreader agreement. Overall
      survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier
      plots with a Mantel-Cox log-rank test and Gehan Breslow Wilcoxon test for
      comparisons. RESULTS: Of the 214 patients, 175 were men and 39 were women. There
      was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall,
      left neck, right neck, and primary tumor site response scores, respectively. The
      corresponding kappa coefficients for interreader agreement between readers were,
      0.69-0.79, 0.68-0.83, 0.69-0.87, and 0.79-0.86 for overall, left neck, right
      neck, and primary tumor site response, respectively. The sensitivity,
      specificity, positive predictive value, negative predictive value, and overall
      accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%,
      respectively. Cox multivariate regression analysis showed human papillomavirus
      (HPV) status and PET/CT interpretation were the only factors associated with PFS
      and OS. Among the HPV-positive patients (n = 123), there was a significant
      difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03-0.57; P
      = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00-0.13; P = 0.0006)
      between the patients who had a score negative for residual tumor versus positive
      for residual tumor. A similar significant difference was observed in PFS and OS
      for all patients. There was also a significant difference in the PFS of patients
      with PET-avid residual disease in one site versus multiple sites in the neck (HR,
      0.23; log-rank P = 0.004). CONCLUSION: The Hopkins 5-point qualitative therapy
      response interpretation criteria for head and neck PET/CT has substantial
      interreader agreement and excellent negative predictive value and predicts OS and
      PFS in patients with HPV-positive HNSCC.

PMID- 24947060
TI  - Analysis of biodistribution of intracranially infused radiolabeled interleukin-13
      receptor-targeted immunotoxin IL-13PE by SPECT/CT in an orthotopic mouse model of
      human glioma.
AB  - Interleukin-13 Pseudomonas exotoxin (IL-13PE), a targeted agent for interleukin
      13 receptor alpha2 (IL-13Ralpha2)-expressing tumors, has been administered
      intracranially by convection-enhanced delivery (CED) for glioma therapy in
      several clinical trials including a randomized phase 3 clinical trial. However,
      its intracranial distribution was not optimally evaluated. We investigated the
      intracranial distribution of radiolabeled IL-13PE after CED in a murine model of
      glioblastoma multiforme. METHODS: IL-13PE was radiolabeled with Na(125)I and
      evaluated for its activity in vitro in receptor-positive U251 or -negative T98G
      human glioma cell lines. Gliomas were grown in nude mice after intracranial
      implantation with U251 cells, and (125)I-IL-13PE was stereotactically
      administered by bolus or CED for 3 d, followed by micro-SPECT/CT imaging. SPECT
      images were evaluated quantitatively and compared with histology and
      autoradiography results. RESULTS: The radioiodination technique resulted in a
      specific and biologically active (125)I-IL-13PE, which bound and was cytotoxic to
      IL-13Ralpha2-positive but not to IL-13Ralpha2-negative tumor cells. Both the
      binding and the cytotoxic activities were blocked by a 100-fold excess of IL-13,
      which indicated the specificity of binding and cytotoxicity. SPECT/CT imaging
      revealed retention of (125)I-IL-13PE administered by CED in U251 tumors and
      showed significantly higher volumes of distribution and maintained detectable
      drug levels for a longer period of time than the bolus route. These results were
      confirmed by autoradiography. CONCLUSION: IL-13PE can be radioiodinated without
      the loss of specificity, binding, or cytotoxic activity. Intracranial CED
      administration produces a higher volume of distribution for a longer period of
      time than the bolus route. Thus, CED of IL-13PE is superior to bolus injection in
      delivering the drug to the entire tumor.

PMID- 24947062
TI  - An integrated quad-modality molecular imaging system for small animals.
AB  - We developed a novel integrated quad-modality system that included 3 molecular
      imaging methods (PET, SPECT, and fluorescence molecular imaging [FMI]) and 1
      anatomic imaging modality (CT). This system could study various biologic
      processes in the same animal using multiple molecular tracers. In addition to the
      technology development, we also discussed the optimization strategy of the
      imaging protocols. The performance of this system was tested, and the in vivo
      animal experiment showed its power to trace 3 different molecular probes in
      living tissues. Our results demonstrated that this system has a great potential
      for the preclinical study of diseases. METHODS: A prototype system integrating
      PET, SPECT, CT, and a charge-coupled device-based free-space FMI system has been
      developed. Imaging and fusion capabilities of the system were evaluated by a
      multimodality phantom. In addition, a mouse disease model with both tumor and
      inflammation was studied by this system to examine the in vivo performance. The 3
      types of molecular probes-(18)F-FDG, [(99m)Tc(HYNIC-3PRGD2)(tricine)(TPPTS)]
      ((99m)Tc-3PRG2) (HYNIC = 6-hydrazinonicotinyl; TPPTS = trisodium
      triphenylphosphine-3,3',3"-trisulfonate; 3PRGD2 = PEG4-E[PEG4-c(RGDfK)]2), and 3
      (triethoxysilyl) propyl-Cy7-entrapped core-cross-linked polymeric micelle (Cy7
      entrapped CCPM) nanoparticles-were used to target 3 different biologic processes
      in the tumor caused by pulmonary adenocarcinoma A549 cells. Moreover, the
      strategy to optimize multimodal molecular imaging procedure was studied as well,
      which could significantly reduce the total imaging time. RESULTS: The imaging
      performance has been validated by both phantom and in vivo animal experiments.
      With this system and optimized imaging protocol, we successfully differentiated
      diseases that cannot be distinguished by a single molecular imaging modality.
      CONCLUSION: We developed a novel quad-modality molecular imaging system that
      integrated PET, SPECT, FMI, and CT imaging methods to obtain whole-body
      multimodality images of small animals. The imaging results demonstrated that this
      system provides more comprehensive information for preclinical biomedical
      research. With optimized imaging protocols, as well as novel molecular tracers,
      this quad-modality system can help in the study of the physiology mechanism at an
      unprecedented level.

PMID- 24947061
TI  - Safety analysis of 10 clinical trials and for 13 years after first approval of
      ioflupane 123I injection (DaTscan).
AB  - Ioflupane is an analog of cocaine that binds reversibly with high affinity to the
      dopamine transporter (DaT) protein, a marker for presynaptic terminals in
      dopaminergic nigrostriatal neurons. Ioflupane (123)I Injection is also known as
      DaTscan or DaTSCAN ((123)I-ioflupane is also called (123)I-2-beta-carbomethoxy
      3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or (123)I-FP-CIT). The
      diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a
      comprehensive analysis of the safety of DaTscan starting from initiation of
      clinical development through 13 y after the date of first market approval. Safety
      data in the sponsor's clinical development safety database from 10 completed
      DaTscan clinical trials were pooled, and postapproval experience was summarized
      from standardized aggregate safety reports submitted to regulatory agencies. A
      total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive
      DaTscan in the clinical trials) received DaTscan. Percentages of subjects with
      adverse events by category were as follows: all (22%), considered at least
      possibly related to DaTscan by the investigator (4%), any severe (3%), headache
      (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site
      hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5
      subjects (<1%) had serious adverse events that led to death. All serious adverse
      events, including those that led to death, were deemed by an expert clinician to
      be unrelated to DaTscan. An estimated half a million market doses of DaTscan (for
      single use) were administered from July 2000 through the July 2013 reporting
      period. In postapproval safety assessment, 1 death was reported 20 d after (and
      unrelated to) DaTscan administration. Two spontaneously reported serious adverse
      drug reactions (ADRs) and 32 spontaneously reported nonserious ADRs were
      submitted, approximately half of which are identified in labeling. Headache (in
      clinical trials) and injection site pain (postapproval) were the most commonly
      reported events or reactions. Although adverse events were reported for 1 in 5
      clinical trial subjects, most were mild and considered unrelated to DaTscan
      administration. Severe events were uncommon, and no serious adverse event
      occurring in more than 1 subject was deemed related to DaTscan administration. In
      postapproval experience, the frequency of ADRs spontaneously reported was less
      than 1 per 10,000 doses administered. Comprehensive safety data show that DaTscan
      was well tolerated.

PMID- 24947063
TI  - The zebrafish/tumor xenograft angiogenesis assay as a tool for screening anti
      angiogenic miRNAs.
AB  - The zebrafish/tumor xenograft angiogenesis assay is used to approach tumor
      angiogenesis, a pivotal step in cancer progression and target for anti-tumor
      therapies. Here, we evaluated whether the assay could allow the identification of
      microRNAs having an anti-angiogenic potential. For that, we transfected DU-145
      prostate cancer cells with four microRNAs (miR-125a, miR-320, miR-487b, miR-492)
      responsive to both anti- and pro-angiogenic stimuli applied to human umbilical
      vein endothelial cells. After transfection, DU-145 cells were injected close to
      the developing subintestinal vessels of transgenic Tg(Kdrl:eGFP)s843 zebrafish
      embryos that express green fluorescent protein under the control of Kdrl
      promoter. At 72 h post-fertilization, we observed that green fluorescent protein
      positive neo-vessels infiltrated the graft of DU-145 transfected with miR-125a,
      miR-320, and miR-487b. Vice versa, neo-vessel formation and tumor cell
      infiltration were inhibited when DU-145 cells transfected with miR-492 were used.
      These results indicated that the zebrafish/tumor xenograft assay was adequate to
      identify microRNAs able to suppress the release of angiogenic growth factors by
      angiogenic tumor cells. 

PMID- 24947064
TI  - Family-based analysis of INSR polymorphisms in Chinese PCOS.
AB  - The insulin receptor (INSR), which is an indispensable component of the insulin
      signalling pathway, could be a plausible candidate gene for polycystic ovary
      syndrome (PCOS). This study was designed to determine whether an association
      exists between three SNP variants (rs3786681, rs17253937 and rs2252673) of the
      INSR gene and PCOS in Han Chinese. A total of 224 family trios (672 participants
      in total) were enrolled in this family-based transmission disequilibrium test.
      Genotypes were obtained by sequencing. A weak association was detected in
      rs2252673 (P = 0.027), which indicated that INSR may confer an increased
      susceptibility to PCOS in Chinese. Additionally, the association between INSR
      gene variants and clinical and metabolic characteristics of women with PCOS was
      investigated. Carriers of the CG and GG genotypes in women with PCOS were
      slightly associated with higher cholesterol concentration (t = 2.072, P = 0.048)
      and lower high-density lipoprotein cholesterol concentration (t = 2.274, P =
      0.026). The minor allele conferred increased odds of PCOS independently of body
      mass index. The present data may provide a basis for further studies of the role
      of the INSR in the aetiology of PCOS. 

PMID- 24947065
TI  - Quality of additional embryos transferred on pregnancy outcomes in IVF:
      predictions using a mathematical approach.
AB  - This study assessed the influence of adding embryos with different embryo quality
      on pregnancy rate and multiple pregnancy rate (MPR). The study included 1891 IVF
      transfers performed at two centres with different embryo transfer policies.
      Pregnancy rate and MPR were analysed following three models and then including
      embryo quality. A predictive mathematical model and two scatter plots were
      constructed. The model based on embryo independence was incompatible with the
      observed data, while both the ground and collaborative models provided excellent
      fits. The collaborative model, however, predicted multiple pregnancies,
      especially triplets, more accurately. Transfer of additional embryos,
      irrespective of embryo quality, always increased pregnancy rate and MPR. When
      implantation rate was low, there was a marked increase in pregnancy rate but only
      a relatively small increase in MPR. In contrast, with higher implantation rates,
      the increase in pregnancy rate was mainly due to the increase in MPR, with the
      same singleton pregnancy rate. Transfer of additional embryos, irrespective of
      embryo quality, follows a collaborative pattern and always results in an increase
      in pregnancy rate and MPR. The scatter plots accurately predicted the influence
      of the different combinations of number and embryo quality on pregnancy rate and
      MPR. 

PMID- 24947066
TI  - Low-dosage clomiphene reduces premature ovulation rates and increases transfer
      rates in natural-cycle IVF.
AB  - Natural-cycle IVF has been suggested as an alternative IVF treatment. However,
      efficacy is limited due to high premature ovulation rates, resulting in low
      transfer rates. This study investigates whether low dosages of clomiphene citrate
      reduce premature ovulation rate and increase transfer rate. Of 112 women included
      (aged 35.2 +/- 4.5 years) 108 underwent one natural-cycle IVF cycle with human
      chorionic gonadotrophin (HCG) to induce ovulation and 103 underwent one natural
      cycle IVF cycle with 25 mg/day clomiphene from about day 7 until HCG
      administration. Before retrieval, 1.2 monitoring consultations per cycle were
      required. Clomiphene reduced premature ovulation rate, from 27.8% without to 6.8%
      with clomiphene (P < 0.001) and increased transfer rate from 39.8% to 54.4% (P =
      0.039). Clinical pregnancy rates without and with clomiphene were 27.9% versus
      25.0% per transfer and 11.1% versus 13.6% per initiated cycle. Use of clomiphene
      resulted in mild hot flushes and headache in 5% of patients. Nausea and
      persisting ovarian cyst formation was not observed. In conclusion, clomiphene
      citrate led to very few side effects, required 1.2 monitoring consultations,
      significantly reduced premature ovulation rate and significantly increased
      transfer rate per initiated cycle, an effect which was not age dependent.

PMID- 24947067
TI  - Is there a critical endometrioma size associated with reduced ovarian
      responsiveness in assisted reproduction techniques?
AB  - This study investigated the relationships between ovarian endometrioma size,
      ovarian responsiveness and the number of retrieved oocytes following ovarian
      stimulation. A prospective study was conducted in a public clinical assisted
      reproduction centre. A total of 64 infertile women with monolateral endometriomas
      undergoing IVF or intracytoplasmic sperm injection were included in the study.
      The total number of follicles, number of follicles >= 16 mm and number of oocytes
      retrieved of ovaries containing endometrioma and normal ovaries were compared.
      Multivariate linear regression was used to assess whether number of follicles and
      collected oocytes varied by endometrioma size, age, basal FSH concentration.
      Significantly lower numbers of follicles >= 16 mm (P = 0.024) and oocytes
      retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In
      patients with endometriomas >= 30 mm, endometrioma size was the most influential
      contributor to the total number of follicles and oocytes retrieved. Ovarian
      endometriomas result in reduced response to ovarian stimulation, compared with
      the response of the contralateral normal ovary in the same individual. In case of
      endometriomas <30 mm, basal FSH concentration remains the most important
      prognostic factor for oocyte retrieval.

PMID- 24947068
TI  - Factors influencing nursing students' acceptance of electronic health records for
      nursing education (EHRNE) software program.
AB  - The Institute of Medicine (IOM) and the Health Information Technology Act (2009)
      in America had recommended that electronic health records (EHRs) should be fully
      adopted by 2014. This has urged educational institutions to prepare healthcare
      professionals to be competent in using electronic health records (EHRs) while
      they are in schools. To equip nursing students with competency in using EHRs, an
      electronic health record for nursing education (EHRNE) has been developed and
      integrated it into nursing curricula. The purposes of the study were to
      investigate the factors influencing nursing students' acceptance of the EHRs in
      nursing education using the extended Technology Acceptance Model with self
      efficacy as a conceptual framework. The study is a descriptive study design using
      self-reported questionnaires with 212 student participants. The IBM SPSS and AMOS
      22.0 were used to analyze the data. The results showed that attitude toward using
      the EHRNE was the most influential factor on students' acceptance. The
      preliminary findings suggested that to enhance the students' acceptance of the
      EHRNE, cultivation of a positive attitude toward using this EHR as well as
      increasing the perceived usefulness is very important. Also, the study's
      framework could be used in guiding learning health informatics and be applied to
      nursing students. 

PMID- 24947069
TI  - Expression of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in
      response to environmental gut conditions.
AB  - Cell surface pili have recently been found in many different bifidobacterial
      species, including the infant gut commensal Bifidobacterium bifidum PRL2010. Pili
      produced by PRL2010 have been shown to be important molecular mediators for
      bacterial interaction with its human host. However, nothing is known about the
      modulation of their expression in response to cues that reflect the gastro
      intestinal environment, such as thermal, acidic, and osmotic challenges, or the
      presence of other gut microorganisms. Here, we investigated how different stress
      conditions that simulate the gastrointestinal niche influence the expression of
      PRL2010 sortase-dependent pili, and how this may impact on the coexistence and
      interaction with other human gut commensals.

PMID- 24947070
TI  - Investigation of treadmill and overground running: implications for the
      measurement of oxygen cost in children with developmental coordination disorder.
AB  - Differences in the kinematics and kinetics of overground running have been
      reported between boys with and without developmental coordination disorder (DCD).
      This study compared the kinematics of overground and treadmill running in
      children with and without DCD to determine whether any differences in technique
      are maintained, as this may influence the outcome of laboratory treadmill studies
      of running economy in this population. Nine boys with DCD (10.3 +/- 1.1 year) and
      10 typically developing (TD) controls (9.7 +/- 1 year) ran on a treadmill and
      overground at a matched velocity (8.8 +/- 0.9 km/h). Kinematic data of the trunk
      and lower limb were obtained for both conditions using a 12-camera Vicon MX
      system. Both groups displayed an increase in stance time (p < 0.001), shorter
      stride length (p < 0.001), higher cadence (p < 0.001) and reduced ankle plantar
      flexion immediately after toe-off (p < 0.05) when running on the treadmill
      compared with overground. The DCD group had longer stance time (p < 0.009) and
      decreased knee flexion at mid-swing (p = 0.04) while running overground compared
      to their peers, but these differences were maintained when running on the
      treadmill. Treadmill running improved ankle joint symmetry in the DCD group
      compared with running overground (p = 0.019). Overall, these findings suggest
      that there are limited differences in joint kinematics and lower limb symmetry
      between overground and treadmill running in this population. Accordingly,
      laboratory studies of treadmill running in children with DCD are likely
      representative of the energy demands of running.

PMID- 24947071
TI  - Effects of supportive hand contact on reactive postural control during support
      perturbations.
AB  - There are many everyday situations in which a supportive hand contact is required
      for an individual to counteract various postural perturbations. By emulating
      situations when balance of an individual is challenged, we examined functional
      role of supportive hand contact at different locations where balance of an
      individual was perturbed by translational perturbations of the support surface.
      We examined the effects of handle location, perturbation direction and
      perturbation intensity on the postural control and the forces generated in the
      handle. There were significantly larger centre-of-pressure (CoP) displacements
      for perturbations in posterior direction than for perturbations in anterior
      direction. Besides, the perturbation intensity significantly affected the peak
      CoP displacement in both perturbation directions. However, the position of the
      handle had no effects on the peak CoP displacement. On the contrary, there were
      significant effects of perturbation direction, perturbation intensity and handle
      position on the maximal force in the handle. The effect of the handle position
      was significant for the perturbations in posterior direction where the lowest
      maximal forces were recorded in the handle located at the shoulder height. They
      were comparable to the forces in the handle at eye height and significantly lower
      than the forces in the handle located either lower or further away from the
      shoulder. In summary, our results indicate that although the location of a
      supportive hand contact has no effect on the peak CoP displacement of healthy
      individuals, it affects the forces that an individual needs to exert on the
      handle in order to counteract support perturbations. 

PMID- 24947072
TI  - Ankle-foot orthoses that restrict dorsiflexion improve walking in polio survivors
      with calf muscle weakness.
AB  - In polio survivors with calf muscle weakness, dorsiflexion-restricting ankle-foot
      orthoses (DR-AFOs) aim to improve gait in order to reduce walking-related
      problems such as instability or increased energy cost. However, evidence on the
      efficacy of DR-AFOs in polio survivors is lacking. We investigated the effect of
      DR-AFOs on gait biomechanics, walking energy cost, speed, and perceived waking
      ability in this patient group. Sixteen polio survivors with calf muscle weakness
      underwent 3D-gait analyses to assess gait biomechanics when walking with a DR
      AFOs and with shoes only. Ambulant registration of gas-exchange during a 6 min
      walk test determined walking energy cost, and comfortable gait speed was
      calculated from the walked distance during this test. Perceived walking ability
      was assessed using purposely-designed questionnaires. Compared with shoes-only,
      walking with the DR-AFOs significantly increased forward progression of the
      center of pressure (CoP) in mid-stance and it reduced ankle dorsiflexion and knee
      flexion in mid- and terminal stance (p < 0.05). Furthermore, walking energy cost
      was lower (-7%, p = 0.052) and gait speed was higher (p = 0.005). Patients were
      significantly more satisfied, felt safer, and less exhausted with the DR-AFO,
      compared to shoes-only (p < 0.05). DR-AFO effects varied largely across patients.
      Patients who walked with limited forward CoP progression and persisting knee
      extension during the shoes-only condition seemed to have benefitted least from
      the DR-AFO. In polio survivors with calf muscle weakness, DR-AFOs improved gait
      biomechanics, speed, and perceived walking ability, compared to shoes-only.
      Effects may depend on the shoes-only gait pattern, therefore further study is
      needed to determine which patients benefit most from the DR-AFO.

PMID- 24947073
TI  - Cloquet's node trumps imaging modalities in the prediction of pelvic nodal
      involvement in patients with lower limb melanomas in Asian patients with palpable
      groin nodes.
AB  - Patients with clinically palpable lymph node metastases to the groin are treated
      with groin dissection to control local disease and stage the malignancy. However,
      the extent of nodal dissection required to optimize survival rate is
      controversial. AIM: To evaluate the approach to the extent of nodal dissection in
      advanced lower limb melanomas with clinically palpable inguinal nodes; to review
      survival outcomes based on the extent of nodal dissection and nodal disease.
      MATERIALS AND METHODS: A prospectively maintained database of 12 patients with
      lower limb melanoma was analyzed. Cloquet's node was assessed based on the frozen
      section result which guided the decision to proceed to iliac-obturator
      dissection. The correlation of the results of the Cloquet's nodes and
      radiological imaging to the final histological outcome of groin nodal dissection
      were compared. RESULTS: The positive predictive value (PPV) of radiological
      imaging in identifying pelvic nodal disease was 60%. PPV of a positive or
      indeterminate frozen section result of Cloquet's node was 71.4%. Notably, all
      patients with a positive frozen section result for the Cloquet's node had
      positive pelvic nodal disease. Median DFS for all patients is 26 months (range 3
      68 months) and the median OS for all patients is 28.5 months (range 5-68 months).
      Median DFS for node negative patients was 28 months (range 24-68 months). Median
      DFS for node positive patients was 20 months (range 3-36 months). CONCLUSION:
      Cloquet's node was shown to be superior to radiological imaging and should be
      preferentially used to decide on the extent of nodal dissection.

PMID- 24947074
TI  - Implementation of complete mesocolic excision at a university hospital in
      Denmark: An audit of consecutive, prospectively collected colon cancer specimens.
AB  - AIM: Over recent years there has been a new focus on the quality of colon cancer
      surgery following the description and introduction of complete mesocolic excision
      (CME). In the same period, laparoscopic surgery has been widely applied to the
      treatment of colon cancer. We aimed to evaluate the introduction of both CME and
      laparoscopic-assisted surgery at Aarhus University Hospital, Denmark between 2008
      and 2011. Secondly we aimed to evaluate the impact on the quality of surgery of
      post-operative team meetings where pathologists demonstrated the plane of surgery
      on the specimens. METHOD: A series of 209 consecutive and prospectively collected
      colon cancer specimens were evaluated by assessing the plane of surgery and
      measuring the amount of tissue resected. Multivariate analyses were used to
      control for influencing factors. RESULTS: The proportion of specimens resected in
      the mesocolic plane was high and increased significantly following the
      introduction of post-operative team meetings (52%-76%, p = 0.02). Laparoscopic
      surgery enhanced the distance between the tumour and the arterial tie by a mean
      of 27 mm (p < 0.0001) and the distance between the nearest bowel wall and the
      arterial tie by 26 mm (p < 0.0001) when compared to an open approach. Factors
      such as body mass index and age influenced the outcome for surgical quality.
      CONCLUSION: Implementation of CME and laparoscopic-assisted surgery for colon
      cancer is a challenge and requires continuous training and feedback. Post
      operative multidisciplinary team meetings may be a key element in this process.

PMID- 24947075
TI  - Castleman's disease of the kidney: Sonographic findings.
AB  - We report a case of rare Castleman's disease of the kidney that mimicked a renal
      neoplasm with emphasis on the imaging and histologic findings. A 47-year-old man
      presented with dyspeptic symptoms. Ultrasound revealed a vascular, heterogeneous
      mass in the left kidney. Multiphasic CT scan confirmed an enhancing lesion with
      enlarged left para-aortic lymph nodes suspicious for nodal metastases. The
      provisional diagnosis was renal cell carcinoma. Percutaneous biopsy yielded a
      diagnosis of Castleman's disease of the hyaline-vascular type. Despite
      advancement in imaging modalities, differentiation of hyaline-vascular variant of
      Castleman's disease from hypervascular renal neoplasm remains difficult and the
      final diagnosis requires histopathological confirmation.

PMID- 24947076
TI  - Differential reparative phenotypes between zebrafish and medaka after cardiac
      injury.
AB  - BACKGROUND: Zebrafish have the ability for heart regeneration. However, another
      teleost animal model, the medaka, had not yet been investigated for this
      capacity. RESULTS: Compared with zebrafish, the medaka heart responded
      differently to an injury: An excessive fibrotic response occurred in the medaka
      heart, and existing cardiomyocytes or cardiac progenitor cells remained dormant,
      resulting in no numerical difference between the uncut and injured heart with
      respect to the number of EdU-incorporated cardiomyocytes. The results obtained
      from the analysis of the medaka raldh2-GFP transgenic line showed a lack of
      raldh2 expression in the endocardium. Regarding periostin expression, the
      localization of medaka periostin-b, a marker of fibrillogenesis, in the medaka
      heart remained at the wound site at 30 dpa; whereas zebrafish periostin-b was no
      longer localized at the wound but was detected in the epicardium at that time.
      CONCLUSIONS: Compared with zebrafish heart regeneration, the medaka heart
      phenotypes suggest the possibility that the medaka could hardly regenerate its
      heart tissue or that these phenotypes for heart regeneration showed a delay.

PMID- 24947077
TI  - Could ocean currents be responsible for the west to east spread of aquatic
      invasive species in Maritime Canadian waters?
AB  - The circulation in the shelf seas of Maritime Canada is predominantly in the
      northeast-southwest direction. Despite the mean northeast-southwest flow, a
      number of AIS invasions have been observed to proceed in the opposite direction -
      from the Gulf of Maine, around Nova Scotia, and into the southern Gulf of St.
      Lawrence. Flow fields from a numerical circulation model are used to investigate
      whether these invasions could be due to drift in ocean currents. Particle
      tracking experiments are performed and probability density functions (PDFs)
      derived that describe the probability of drifting a given upstream distance in a
      given drift time. Analysis of these PDFs revealed that for invasions that took 20
      40 y to occur, propagule drift in ocean currents could be responsible for the
      upstream spread, while this was not the case for short timescale invasions (<10
      y). Rafting could be responsible for both short and long timescale invasions.

PMID- 24947078
TI  - A cell biological view of the siderophore pyochelin iron uptake pathway in
      Pseudomonas aeruginosa.
AB  - Pyochelin (PCH) is a siderophore produced and secreted by Pseudomonas aeruginosa
      for iron capture. Using (55) Fe uptake and binding assays, we showed that PCH-Fe
      uptake in P. aeruginosa involves, in addition to the highly studied outer
      membrane transporter FptA, the inner membrane permease FptX, which recognizes PCH
      (55) Fe with an affinity of 0.6 +/- 0.2 nM and transports the ferri-siderophore
      complex from the periplasm into the cytoplasm: fptX deletion inhibited (55) Fe
      accumulation in the bacterial cytoplasm. Chromosomal replacement was used to
      generate P. aeruginosa strains producing fluorescent fusions with FptX, PchR (an
      AraC regulator), PchA (the first enzyme involved in the PCH biosynthesis) and
      PchE (a non-ribosomic peptide-synthetase involved in a further step).
      Fluorescence imaging and cellular fractionation showed a uniform repartition of
      FptX in the inner membrane. PchA and PchE were found in the cytoplasm, associated
      to the inner membrane all over the bacteria and also concentrated at the
      bacterial poles. PchE clustering at the bacterial poles was dependent on PchA
      expression, but on the opposite PchA clustering and membrane association was PchE
      independent. PchA and PchE cellular organization suggests the existence of a
      siderosome for PCH biosynthesis as previously proposed for pyoverdine
      biosynthesis (another siderophore produced by P. aeruginosa). 

PMID- 24947079
TI  - Identification of patients with a histologically unstable carotid plaque using
      ultrasonic plaque image analysis.
AB  - OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in
      the first few days after onset of symptoms and it is low in asymptomatic
      patients. The ability to identify patients with a high (or low) probability of
      having a histologically unstable plaque might become a complimentary method that
      can refine the indications for surgical intervention. METHODS: Two
      histopathologists, using validated American Heart Association criteria,
      independently graded plaques harvested during carotid endarterectomy.
      Preoperative Duplex images were independently assessed for juxtaluminal black
      area, plaque type, plaque area, and grey-scale median (GSM) following image
      normalization. Logistic regression analysis was then performed to create a model
      for predicting predominantly histologically unstable or stable plaques. RESULTS:
      A total of 126 patients were included in the study. Based on the presence and
      extent of histological features including haemorrhage, thrombus, fibrous tissue,
      lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques
      were graded as predominantly stable, while 87 were predominantly unstable.
      Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI
      1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to
      6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression
      indicated that patients with the first two features had a 90% probability of
      having a histologically unstable plaque. The model was used to calculate the
      probability of having an unstable plaque in each patient. The receiver operating
      characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS:
      Computerized plaque analysis has the potential to identify patients with
      histologically unstable carotid plaques. This model requires validation, but
      offers the potential to influence patient selection for emergency interventions
      and the monitoring of medical therapy.

PMID- 24947080
TI  - Biochemical and immunomorphological evaluation of hepatocyte growth factor and c
      Met pathway in patients with critical limb ischemia.
AB  - OBJECTIVES: Hepatocyte growth factor (HGF), the c-Met receptor, and hypoxia
      inducible factor (HIF) are crucial for regenerative processes including ischemic
      wound healing. The aims of the present study are (a) to analyze the tissue c-Met
      and HIF-1alpha expression in skin from patients with critical limb ischemia
      (CLI); (b) to compare the serum HGF levels of CLI and control subjects. METHODS:
      This is a prospective, controlled, single-center study. Thirty-seven patients
      were enrolled. A skin sample adjacent to the ischemic lesion was taken from 20
      patients with CLI; skin samples were taken from the surgical wounds of 17
      patients surgically treated for abdominal aortic aneurysm as healthy controls.
      Serum samples were taken in all cases. Samples were formalin fixed, paraffin
      embedded, and routinely processed. Tissue inflammation was histologically
      assessed. Immunohistochemistry was performed with antibodies against total c-Met
      receptor, activated Met (p-Met), and HIF-1alpha. RT-polymerase chain reaction was
      used to quantify HIF-1alpha mRNA. The enzyme-linked immunosorbent assay was
      performed to evaluate serum HGF levels. RESULTS: With immunohistochemistry, while
      total c-Met was unchanged, different patterns of p-Met positivity were observed
      between CLI and control cases (p < .001). In particular, CLI skin showed a total
      negativity or membrane positivity for p-Met (19/20 cases), while control skin
      mainly showed cytoplasmic positivity in the epidermal basal layer (16/17 cases).
      HIF-1alpha was diffusely lost in CLI, but HIF-1alpha mRNA was threefold higher
      than in controls. Finally, mean serum HGF levels were 590.5 pg/mL and 2380.0
      pg/mL in CLI and control groups respectively (p < .001). CONCLUSIONS: In CLI
      patients a significant decrease in serum HGF levels, concomitant with a loss of
      skin HIF-1alpha stabilization and a lack of c-Met phosphorylation were seen,
      probably driving a decrease in wound-healing functions. The next hypothesis is
      that HGF application might reactivate the c-Met receptor, stabilizing the normal
      wound healing process.

PMID- 24947081
TI  - Partial helix defect repair by use of postauricular advancement flap combined
      with ipsilateral conchal cartilage graft.
AB  - OBJECTIVE: The objective of this study is to investigate the usage and
      effectiveness of postauricular advancement flap and conchal cartilage for
      surgical treatment of partial helix defect. METHODS: Ten cases (eight males, two
      females) of unilateral partial ear defects were treated by using postauricular
      advancement flap combined with ipsilateral conchal cartilage graft. Of the 10
      cases, nine cases were due to injury, one case was the result of frostbite. The
      patients ranged in age from 15 to 34 years (mean age=25.4 years). RESULTS: All
      cases were followed up for 3-12 months with satisfactory results, indicated by
      helix and scapha of similar color. No hypertrophic scarring was reported.
      CONCLUSIONS: The use of postauricular advancement flap, combined with ipsilateral
      conchal cartilage graft, is an effective way to repair partial helix defects, and
      a second procedure may be necessary to achieve a symmetrical cranioauricular
      angle.

PMID- 24947082
TI  - Adipogenic differentiation potential of rat adipose tissue-derived subpopulations
      of stromal cells.
AB  - Adipose-derived stromal cells (ASCs) are mostly isolated by enzymatic digestion,
      centrifugation and adherent growth resulting in a very heterogeneous cell
      population. Therefore, other cell types in the cell culture can comprise the
      differentiation and proliferation potential of the ASC population. Recent studies
      indicated that an antibody-aided isolation of distinct ASC subpopulations
      provides advantages over the conventional method of ASC isolation. The aim of
      this study was to investigate the adipogenic differentiation potential of CD29-,
      CD71-, CD73- and CD90-selected ASCs in vitro. The stromal vascular fraction (SVF)
      was obtained from rat adipose tissue by enzymatic digestion and centrifugation.
      Subsequently, CD29(+)-, CD71(+)-, CD73(+)- and CD90(+) cells were isolated by
      magnetic activated cell sorting (MACS), seeded into culture plates and
      differentiated into the adipogenic lineage. ASCs isolated by adherent growth only
      served as controls. Adipogenic differentiation was assessed by Oil Red O staining
      and quantification of the adiponectin and leptin concentrations in the cell
      culture supernatants. Statistical analysis was carried out using one-way analysis
      of variance (ANOVA) followed by the Scheffe's post hoc procedure. The results
      showed that different subpopulations with different adipogenic differentiation
      potentials can be isolated by the MACS procedure. The highest adipogenic
      differentiation potential was determined in the CD29-selected ASC population
      followed by the unsorted ASC population. The CD71-, CD73- and CD90-selected cells
      exhibited significantly the lowest adipogenic differentiation potential. In
      conclusion, the CD29-selected ASCs and the unsorted ASCs exhibited a similar
      adipogenic differentiation potential. Therefore, we do not see a clear advantage
      in the application of an anti-CD29-based isolation of ASCs over the conventional
      technique using adherent growth. However, the research on isolation/purification
      methods of adipogenic ASCs should continue in order to make this stem cell source
      even more attractive for future adipose tissue engineering applications. 

PMID- 24947083
TI  - Characteristic features and natural evolution of Kienbock's disease: five years'
      results of a prospective case series and retrospective case series of 106
      patients.
AB  - OBJECTIVES: Scientific databases index numerous references related to the
      treatment of Kienbock's disease; yet little is known about the nature of the
      disease and its pathognomonic features. This study provides a cross-sectional
      analysis of the pattern and extent of osteonecrosis in a large cohort and a
      longitudinal analysis to determine the spontaneous disease progression in single
      patients who have not had surgical management until fragmentation of the lunate.
      METHODS: In a prospective case series, the pattern and extent of osteonecrosis
      were correlated with the duration of symptoms in all patients with Kienbock's
      disease confirmed using high-resolution 3-T magnetic resonance imaging (MRI) and
      ultra-thin section computed tomographic (CT) scan since 2009. Furthermore, a
      retrospective consecutive case series study was conducted to determine the rate
      of spontaneous evolution in all consecutive patients treated conservatively in
      our university hospital since 1990. RESULTS: Among the 35 consecutive patients
      with Kienbock's disease diagnosed in high-resolution 3-T MRI and ultra-thin
      section CT, 46% (16/35) presented degeneration of lunate cartilage on CT scan in
      the first 12 months following the onset of symptoms. Median wrist pain duration
      of patients presenting a fracture of the lunate was 14 months. Thirty-one percent
      (11/35) of the patients had arthritis of the lunate, yet no fractures at the time
      of examination. Of 106 consecutive patients with Kienbock's disease and complete
      records, who did not have surgical intervention until fragmentation of the
      lunate, three cases were identified with well-documented spontaneous courses from
      apparently intact lunate morphology until fragmentation within 6 months.
      CONCLUSIONS: Kienbock's disease progresses substantially faster than previously
      described and, contrary to current classifications, the articular cartilage of
      the lunate degenerates in early stages. LEVEL OF EVIDENCE: Diagnostic accuracy,
      Level IV.

PMID- 24947084
TI  - Prelaminated fascia lata free flap for large nasal septal defect reconstruction.
AB  - Nasal septal defects can be challenging to repair, given their location, size,
      and the unique, tri-layered structure of the septum, which includes a thin piece
      of cartilage positioned between mucosal layers. The report herein presents a case
      of a 47 year-old woman with a large symptomatic nasal septal perforation, despite
      saline irrigations and ointment. Placement of a septal button or a traditional
      surgical approach was not considered because of the extremely large nature of the
      perforation. We describe the use of a tri-layered fascia lata flap prelaminated
      with buccal mucosa grafts to successfully repair this complicated defect.
      Subsequent follow-up visits showed complete repair of the defect and patent nasal
      passages, without the need for any debulking procedures. Based on these results,
      we conclude that a prelaminated fascia lata flap is a good reconstructive option
      for large, complex nasal septal defects, bringing thin, healthy mucosalized
      tissue to the defect and minimizing future surgical procedures. 

PMID- 24947085
TI  - Mechanistic studies of oxidative decomposition of Angeli's salt and PAPA NONOate.
AB  - Nitric oxide, (.)NO, and product of its one-electron reduction, nitroxyl NO(-),
      are important molecules in the biochemistry of living organisms. At physiological
      conditions nitroxyl exists in its protonated form, HNO. Angeli's salt, AS, and
      diazeniumdiolates, NONOates, are widely used donors of HNO and (.)NO,
      correspondingly. In this work we observed oxidative decomposition of AS and PAPA
      NONOate in the presence of mild oxidizing agents, 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide, cPTIO, and 2,2'-azinobis(3
      ethylbenzolthiazoline-6-sulfonate) radical, ABTS(.-). The observed unexpected
      fast oxidative decomposition of AS with release of NO instead of HNO suggests the
      need for a reevaluation of some of the biological effects of AS assigned to
      action of HNO. While oxidative decomposition of NONOate did not result in release
      of alternative NOx specimen but only (.)NO, it significantly affects the rates
      and stoichiometry of (.)NO release. In summary, possible contribution of
      oxidative decomposition of AS and NONOates should be taken into account upon
      interpretation of their actions in chemical and biological systems.

PMID- 24947086
TI  - Socio-demographic characteristics of cancer patients: hospital based cancer
      registry in a tertiary care hospital of India.
AB  - AIM: To determine the socio-demographic characteristics of cancer patients.
      MATERIALS AND METHODS: Review of the Cancer registry, and patient interview.
      Information on socio-demographic profile, medical history, family history and
      previous treatment, if any, was retrieved from the patient. If the patient
      couldn't be contacted then information was taken from pathology/radiotherapy or
      medical records department. RESULTS: A total of 684 patients participated in the
      study. More than 40% of males and 53.7% of females were illiterate, P < 0.05. The
      majority (33.5%) of participants were of low socioeconomic status. The most
      frequently reported cancer (ca) in males it was ca lung (40.9) and ca oesophagus
      (9.8). In females most common cancer were ca breast (23.9) followed by ca cervix
      (11.7).

PMID- 24947087
TI  - Imatinib mesylate as first-line therapy in patients with chronic myeloid leukemia
      in accelerated phase and blast phase: a retrospective analysis.
AB  - INTRODUCTION: Imatinib is a bcr-abl tyrosine kinase inhibitor which has
      revolutionized the treatment for chronic myeloid leukemia (CML). Even though
      there is much data on CML chronic phase, there is limited data on imatinib
      naomicronve advanced phase CML. MATERIALS AND METHODS: We retrospectively
      analysed 90 patients with advanced phase CML (accelerated phase [AP]: 51 and
      blast crisis [BC]: 39), patients who received imatinib as frontline therapy.
      RESULTS: The median age of presentation in CML-AP and CML-BC were 32 years (12
      61) and 39 years (8-59), respectively. Imatinib at 600 mg/day was initiated
      within 2 weeks of diagnosis. Median time to complete hematological response in
      both CML-AP and CML-BC was 3 months (CML-AP: 1-9 months and CML-BC: 1-14 months).
      At 6 months 30 (59%) CML-AP and 15 (38%) CML-BC patients achieved major
      cytogenetic response (MCyR), of them 24 (47%) and 10 (25.6%) being the complete
      cytogenetic response, respectively. At a median follow-up of 41 months, the
      median overall survival in CML-AP was 61 months, but in CML-BC it was 14 months.
      The median progression-free survival and event-free survival were 30 months and
      23 months in CML-AP and 14 and 12 months in CML-BC, respectively. On univariate
      analysis, performance status (PS), spleen size, and MCyR predicted survival in
      AP, whereas in BC, platelet count, PS, and early MCyR were predictive. Non
      hematologic and hematologic adverse events were observed in 80% and 60% of
      patients, respectively. Dose was reduced in 10% of patients for grade IV toxicity
      and interrupted in 30% for grade III toxicity. CONCLUSION: Front-line imatinib is
      an option in advanced phases of CML especially in CML-AP in low-resource
      countries, where stem cell transplantation and alternate TKIs are not available.

PMID- 24947088
TI  - Efficacy of radical radiotherapy alone for functional preservation of larynx in
      laryngeal carcinoma: a retrospective analysis.
AB  - PURPOSE: Concurrent chemoradiation is the current standard of care in locally
      advanced head and neck cancer. But, in our setup, many patients of carcinoma
      larynx are treated with only radical radiotherapy because of poor general
      condition of the patients. This study was performed to assess the influence
      radical radiotherapy alone on functional preservation of larynx. MATERIALS AND
      METHODS: 110 previously untreated patients with invasive squamous cell carcinoma
      of larynx were treated with radical radiotherapy alone between January 2006 and
      June 2009. Conventional one daily fraction of 2 Gy with total doses of 60-66 Gy
      was used. Voice preservation and local control at median follow-up period of 2
      years were analyzed. Several host, tumor, and treatment parameters were also
      analyzed. RESULTS: Among 110 patients, preservation of larynx was possible in 78
      patients (71%). With radical radiotherapy alone, excellent preservation of larynx
      was achieved in stage I (88.9%) and stage II (75%) disease, while in advanced
      stages, results were not so encouraging. In stage III and stage IVA, larynx
      preservation was only 72.4% and 65.3%, respectively. Patients without any
      cartilage invasion had significantly better laryngeal preservation rate as
      compared to patients with cartilage invasion. (78.9% vs. 35.3%; P = 0.008).
      CONCLUSION: Though concurrent chemoradiation is the standard of care in
      preservation of voice in laryngeal cancer, definitive radiotherapy alone may also
      be a good option in terms of preservation of larynx in patients of laryngeal
      cancer in community practice in the developing world where most of the patients
      cannot tolerate concurrent chemoradiation.

PMID- 24947090
TI  - Plasma cell leukemia: a retrospective study of 10 cases.
AB  - BACKGROUND: Plasma cell leukemia (PCL) is a rare aggressive variant of multiple
      myeloma (MM) characterized by a fulminant course and poor prognosis. Flow
      cytometry (FCM) is very useful in the diagnosis of the plasma cell leukemia.
      Herein, we present 10 cases of PCL. MATERIALS AND METHODS: We retrospectively
      studied immunophenotypic profile of 10 cases of PCL from Jan 2009 to Dec 2013
      using 5 parameters, 6 color flow cytometric analysis. We also studied their
      clinical presentation and other laboratory findings. RESULTS: Common clinical
      features at presentation were weakness, bone pain, anemia, thrombocytopenia and
      osteolytic lesions. Plasma cell population were identified by strong expression
      of CD38 and co-expression of CD38 and CD138. CD56 was expressed in 20% cases.
      CD19 and CD117 were negative in all cases. CONCLUSIONS: Immunophenotyping is
      highly useful to differentiate PCL from other chronic lymphoproliferative
      disorders with plasmacytoid morphology as well as from non-neoplastic reactive
      plasma cells. Co-expression of CD38 and CD138 is a best combination to identify
      the plasma cells by using FCM.

PMID- 24947089
TI  - Staging laparoscopy in gastroesophageal and gastric adenocarcinoma: first
      experience from Pakistan.
AB  - CONTEXT: Current NCCN guidelines do not consider staging laparoscopy mandatory
      for detection of metastasis in gastroesophageal junction (GEJ) and gastric
      cancer. AIMS: To determine the rate of detection of metastasis on staging
      laparoscopy in GEJ and gastric cancer in Pakistani population and determine the
      prognostic significance of cytology versus biopsy positive metastatic disease.
      SETTINGS AND DESIGN: Retrospective study conducted from January 2005 to June
      2013. MATERIALS AND METHODS: Demographics, clinicopathological characteristics
      and laparoscopic findings of 149 patients were compared. STATISTICAL ANALYSIS
      USED: Categorical variables were represented as frequencies and percentages and
      significance was determined using Chi square test. Overall survival was
      calculated from the date of staging laparoscopy to the date of death/last follow
      up. Survival for cytology versus biopsy positive metastatic disease was
      calculated using Kaplan Meier curves and significance determined with Log rank
      test. RESULTS: Overall, metastases were detected in 40% of patients on staging.
      Laparoscopy detected metastasis in significantly high number of gastric cancers
      (48% versus 28%) (P = 0.01). Peritoneal nodules were more frequent with gastric
      tumors (40% versus 23%) and also were more likely to be malignant (58% versus
      35%). Expected one year survival in patients with positive cytology (peritoneal
      washing/ascitic fluid) was significantly higher than patients with a positive
      peritoneal nodule biopsy (29% versus 0) (P = 0.04). On univariate analysis this
      was the only significant factor for increased risk of death (P = 0.03, HR = 2.5,
      CI = 1.04-5.98). CONCLUSIONS: Staging laparoscopy detects metastatic disease in a
      significant number of patients deemed non metastatic on preoperative imaging.
      Prognostically, cytology positive metastatic cancer may be different from biopsy
      positive cancer.

PMID- 24947091
TI  - Weekly chemotherapy as Induction chemotherapy in locally advanced head and neck
      cancer for patients ineligible for 3 weekly maximum tolerable dose chemotherapy.
AB  - OBJECTIVE: To study the safety and efficacy of weekly chemotherapy as part of
      induction chemotherapy, in locally advanced head and neck cancer for patients,
      who are unfit for upfront radical treatment. MATERIALS AND METHODS: It is a
      retrospective analysis of on-use weekly chemotherapy as Induction chemotherapy in
      locally advanced head and neck cancer, who are technically unresectable are unfit
      for upfront radical treatment. Induction chemotherapy given was a 2 drug
      combination of paclitaxel (80 mg/m 2 ) and carboplatin AUC 2. The decision to
      give weekly induction chemotherapy was given on the basis of presence of 2 more
      following features: Poor performance status (ECOG PS 2-3), presence of
      uncontrolled co morbidities, BMI below 18.5 kg/m 2 and age more than 60 years.
      The Statistical Package for the Social Sciences software (SPSS version 16.0) was
      used for analysis. The response rates, toxicity (accordance with CTCAE vs. 4.02),
      completion rate (Cp) of radical intent treatment post neoadjuvant chemotherapy
      (NACT), progression-free survival (PFS) and overall survival (OS) are reported.
      RESULTS: Fifteen patients were considered for such therapy. Fourteen out of
      fifteen patients completed NACT. The median numbers of planned weekly cycles were
      6 (3-8). Response (CR + PR) was seen in 10 patients. Overall grade 3-4 toxicity
      was seen in 6 patients. No toxicity related mortality was noted. The calculated
      completion rate (Cp) of radical intent treatment post NACT was 46.7%. The median
      PFS and OS were 10.36 months (95% CI 6.73-14.00 months) and 16.53 months (95% CI
      4.22-28.84). CONCLUSION: Use of induction chemotherapy with weekly regimen is
      safe and effective selected cohort of patients with locally advanced disease who
      are unfit for upfront radical treatment.

PMID- 24947092
TI  - Correlation of clinico-pathologic and radiologic parameters of response to
      neoadjuvant chemotherapy in breast cancer.
AB  - CONTEXT: As of today, there is no validated standard method to assess clinical
      response of breast cancer to neo- adjuvant chemotherapy (NACT). Some centers use
      clinical dimensions while others use radiological measurements to evaluate
      response according to RECIST criteria. AIMS: The aim was to correlate and compare
      the clinical, radiological, and pathological parameters for assessing the tumor
      response in patients of breast cancer receiving NACT. SETTINGS AND DESIGN: Single
      institution, prospective nonrandomized study conducted over a 2-year period.
      MATERIALS AND METHODS: Patients with diagnosed breast cancer were assessed for
      response to NACT prior to surgery using clinical and radiological techniques.
      This was correlated with pathological reponse which was assessed by measuring
      gross dimensions and Miller-Payne grading of response to chemotherapy.
      STATISTICAL ANALYSIS USED: Spearman's rho nonparametric. RESULTS: Fifty two
      patients completed the evaluation (out of 313 cases of ca breast treated during
      the same period) with a median age of 52.5 years. We noted a 26.9% clinical
      complete response (CR) and 19.2% had pathological CR. Clinical evaluation had a
      sensitivity and specificity of 73.5% and 88.5% respectively compared to 14.2% and
      100% respectively for radiological assessment. CONCLUSIONS: Clinical assessment
      of response to NACT shows a higher sensitivity compared to radiological
      assessment. However the overall low sensitivity and specificity rates of clinical
      assessment mandate a search for a better method of evaluation.

PMID- 24947093
TI  - Non-haematopoietic malignancies metastasing to the bone marrow: a 5 year record
      based descriptive study from a tertiary care centre in South India.
AB  - INTRODUCTION: Bone marrow involvement by a non-haematological malignancy gives an
      opportunity to identify the lodgement, invasion of metastatic cells and the
      response of the host to the tumor cells. The study was undertaken to assess the
      involvement of bone marrow with non-haematopoietic malignancies and its
      significance in establishing primary diagnosis in clinically unsuspected cases.
      MATERIALS AND METHODS: This was a descriptive study which included record review
      of the departmental archives for the last five years (January 2007 to December
      2011). Eighty four cases were studied; which included clinically diagnosed non
      haematological malignancy for staging or symptomatic cytopenias/bony lesions
      (group 1, n = 63), clinically suspected bone marrow metastasis of unknown primary
      malignancy due to symptomatic cytopenias/bony lesions (group 2, n = 07) and
      clinically unsuspected malignancy with incidentally detected bone marrow
      metastasis (group 3, n = 14). RESULTS: Bone marrow metastases of solid tumors
      were identified in 23 cases (27.3%) which included 9 cases from group 1, 14 cases
      from group 3 and nil in group 2. Of the 14 cases in group 3, in 12 cases a
      definitive diagnosis could be made by correlating clinicoradiological findings
      with morphology and immunohistochemistry. The most common tumor in pediatric
      cases were neuroblastoma and Ewing's sarcoma (40%) and in adult's adenocarcinoma
      of gastrointestinal tract (30.7%) was the commonest. CONCLUSION: Bone marrow
      metastasis can masquerade as a primary haematopoietic disorder; however its
      detection has both therapeutic and prognostic significance. Immunohistochemistry
      is a useful adjunct to morphology in reaching a definitive diagnosis.

PMID- 24947094
TI  - Gastrointestinal stromal tumor: analysis of outcome and correlation with c-kit
      status in Indian population.
AB  - AIMS: The aim of the present study is to analyse the outcome and genotypic
      pattern of metastatic GIST patients which is largely unknown in India. MATERIALS
      AND METHODS: The present study was a retrospective analysis of 24 patients of
      metastatic GIST. The case records were analysed for clinical profile, treatment
      response and prognostic factors. The archival samples were retrieved for c-kit
      mutation analysis in all but 5 patients for mutation analysis. RESULTS: The
      median age of the study population was 56 years. At a median follow up of 29
      months, the PFS was 45% at 2 years. Activating c-kit mutations were detected in
      10 cases (52.6%). 80% of the mutations were located in Exon 11. CONCLUSIONS: The
      outcome of metastatic GIST patients has definitely improved from a virtually
      incurable state to a disease where median OS has reached 60 months. The genotype
      of Indian patients with GIST may be different from the western population which
      needs to be confirmed in a larger study.

PMID- 24947096
TI  - Spectrum of malignancies in Jaipur region (2004-2008).
AB  - CONTEXT: Cancer data from Rajasthan is limited. Only three studies, one from
      Western Rajasthan, and the other two from Eastern Rajasthan have been published
      previously. AIMS: To find out the spectrum of malignant neoplasms in Jaipur
      region by studying the proportion and site wise distribution of malignancy cases
      reported at five major hospitals and pathology centers in Jaipur region. SETTINGS
      AND DESIGN: A retrospective analysis of histopathology records of 5 years (2004
      2008) was done. Approximately 200,000 histopathology and cytology reports were
      analyzed and 34,486 new cancer cases were identified. STATISTICAL ANALYSIS USED:
      Percentages and proportions. RESULTS: A total of 34,486 new cases of cancers were
      recorded in five years. There were 58.58% (20202) males and 41.42% (14284)
      females, with the male to female ratio being 1.41:1. Organ wise, Lung (13.25%),
      Larynx (5.35%), Oropharynx (5.09%), Brain (4.84%), Tongue (4.62%) and Prostate
      (4%) were the most common sites involved in males, whereas Breast (25.6%), Cervix
      (10.26%), Ovary (5.4%), Brain (3.68%), Esophagus (3.4%), Lung (3.01%) and Gall
      Bladder (2.35%) were common sites for malignancies in females. CONCLUSIONS:
      Significant findings were, a higher frequency of tobacco related cancers i.e.,
      Lung cancer and Head and neck cancer in males, and screening detectable cancers
      (Breast and Cervix) in females. A higher frequency of Lung cancer in females was
      also noted as compared to previous studies. An unusually high frequency of Gall
      Bladder Cancers especially among the female population in this region is also a
      cause of concern. Our data was compared with the national data.

PMID- 24947095
TI  - Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice
      weekly in patients with advanced cancer.
AB  - CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces
      mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is
      being developed for the treatment of solid tumors and hematological malignancies.
      AIMS: To determine the safety, dose-limiting toxicities, and clinical activity of
      rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week
      for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or
      hematological malignancies; and to confirm the safety and tolerability of the
      recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose
      escalation study in men and women >=18 years of age. MATERIALS AND METHODS: An
      escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg
      rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase
      confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data
      summaries were descriptive. PK parameters were estimated using compartmental
      analysis. RESULTS: 25 patients (16 male, 9 female, 26-66 years, all Asian) were
      treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase.
      MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours
      was declared to be the RPTD. Best response was stable disease in 5 of 14
      evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg
      rigosertib as a 4-hour infusion was identified as the RPTD. Five patients
      achieved stable disease lasting 6-16 weeks.

PMID- 24947097
TI  - A retrospective clinicopathological study of 131 cases with endometrial cancers-
      is it possible to define the role of retroperitoneal lymphadenectomy in low
      resource settings?
AB  - AIM: The study objectives were evaluation of clinicopathological characteristics,
      correlations between the preoperative and postoperative tumor grades, and their
      implications on lymph node metastasis. MATERIALS AND METHODS: We conducted a
      retrospective descriptive study of 131 cases of endometrial cancer examined and
      treated at a tertiary regional cancer institute between the years 2003 and 2009.
      We reviewed the oncology database as well as the clinical records and surgico
      pathological registry of all these patients. Statistical Methods Used: All the
      summary measure computation and Chi-square test for comparing more than one
      proportion was done in spreadsheet (Excel). RESULTS: The multiparity association
      with endometrial cancer was commonly seen 113/131 (86.2%). Twelve (9.7%) patients
      preoperatively diagnosed as Grade 1 tumors upgraded to Grade 3 changes in
      postoperative specimens and six of these 12 patients (50%) had lymph node
      metastasis. A total of 14/131 (10.6%) cases had lymph nodes metastasis.
      CONCLUSIONS: There is a poor correlation between the preoperative and the
      postoperative tumor grades. Routine pelvic lymphadenectomy may be a valuable
      method in low-risk cases and para-aortic lymphadenectomy may be limited to high
      risk endometrial cancers.

PMID- 24947098
TI  - Assessment of cosmetic outcome of oncoplastic breast conservation surgery in
      women with early breast cancer: a prospective cohort study.
AB  - BACKGROUND: The aim of this study was to assess the cosmetic outcome of patients
      undergoing oncoplastic breast conserving surgery in Indian population. MATERIALS
      AND METHODS: A prospective cohort of 35 patients who were eligible for breast
      conservation surgery was included in the study from year 2007 to 2009. Patients
      with central quadrant tumors were excluded from the study. A double - blind
      cosmetic assessment was done by a plastic surgeon and a senior nurse not involved
      in the management of patients. Moreover, self-assessment was carried out by the
      patient regarding the satisfaction of surgery, comfort with brasserie, social and
      sexual life after oncoplastic surgery. RESULTS: In this study, 35 patients
      underwent oncoplastic breast conservation surgery by various techniques. The
      cosmetic outcome scores of the surgeon and nurse were analyzed for inter rater
      agreement using inter-class Correlation Coefficients. There was a good
      association between them. The risk factors for poor cosmetic outcome was studied
      by univariate analysis and significant correlation was obtained with age, volume
      of breast tissue excised and estimated percentage of breast volume excised (P <
      0.05). Moreover, 96% of patients were moderately to extremely satisfied with the
      surgery. Patients were offered an option for cosmetic correction of contralateral
      breast by mastopexy or reduction mammoplasty however, none of them agreed for
      another procedure. CONCLUSIONS: Oncoplastic breast surgery helps to resect larger
      volume of tissue with wider margins around the tumor. It helps to achieve better
      cosmesis and extends the indications for breast conservation. Most of the
      patients were satisfied with mere preservation of the breast mound rather than a
      symmetrical contralateral breast.

PMID- 24947099
TI  - Immunohistochemical analysis of thyroid follicular neoplasms and BRAF mutation
      correlation.
AB  - BACKGROUND: The accurate diagnosis of benign and malign thyroid tumors is very
      important for the clinical management of patients. The distinction of thyroid
      papillary carcinoma follicular variant and follicular adenoma can be difficult.
      AIM: To investigate the alternative methods like immunohistochemistry and exon 15
      in the BRAF gene 1799 T/A mutation analyses for distinguishing thyroid tumors.
      MATERIALS AND METHODS: We applied immunohistochemical markers; CK19, HMWCK,
      Galectin-3, HBME-1 and Fibronectin and mutant allele-specific PCR amplification
      technique was used to determine 1799 T/A mutation within the BRAF gene. Formalin
      fixed parafin embedded tissues from 45 surgically total resected thyroids,
      included 26 thyroid papillary carcinoma follicular variant (FV-TPC), 8 Follicular
      Adenoma (FA), 6 Minimal invasive follicular carcinoma (MIFC) and 5 Follicular
      Carcinoma (FC). Statistical Analyses Used: Pearson Chi-Square and Kruskal Wallis
      tests were performed. RESULTS: There was a positive correlation between FV-TPC
      and HMWCK, CK 19, HBME1, Galectin 3, fibronectin (P < 0.05), but there was no
      correlation with FV-TPC and BRAF gene mutation (P > 0.05). HBME-1 and CK 19
      stained strong and diffuse positive in FV-TPCs but weak and focal in FAs.
      CONCLUSION: Our study suggests that morphologic features combined with
      immunohistochemical panel of HMWCK, CK19, HBME-1, Galectin-3 and fibronectin can
      help to distinguish benign and malign thyroid neoplasms and FV-TPC from
      follicular adenomas. BRAF gene 1799 T/A mutation has been non-specific but its
      detection can be a useful tool combined with immunohistochemistry for diagnosing
      FV-TPC.

PMID- 24947100
TI  - Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil
      regimen in technically unresectable oral cancer in resource limited rural based
      tertiary cancer center.
AB  - BACKGROUND: Recent studies indicate neoadjuvant chemotherapy (NACT) can result in
      R0 resection in a substantial proportion of patients with technically
      unresectable oral cavity cancers. However, data regarding the efficacy and safety
      of docetaxel, cisplatin and 5 fluorouracil (TPF) NACT in our setting is lacking.
      The present audit was proposed to evaluate the toxicities encountered during
      administration of this regimen. It was hypothesized that TPF NACT would be
      considered feasible for routine administration if an average relative dose
      intensity (ARDI) of >=0.90 or more in at least 70% of the patients. MATERIALS AND
      METHODS: Technically unresectable oral cancers with Eastern Cooperative Oncology
      Group PS 0-2, with biopsy proven squamous cell carcinoma underwent two cycles of
      NACT with TPF regimen. Toxicity and response rates were noted following the CTCAE
      4.03 and RECIST criteria. Descriptive analysis of completion rates (completing 2
      cycles of planned chemotherapy with ARDI of 0.85 or more), reason for delay,
      toxicity, and response are presented. RESULTS: The NACT was completed by all
      patients. The number of subjects who completed all planned cycles of chemotherapy
      are with the ARDI of the delivered chemotherapy been equal to or >0.85 was 11
      (91.67%). All toxicity inclusive Grade 3-5 toxicity was seen in 11 patients
      (91.67%). The response rate of chemotherapy was 83.33%. There were three complete
      response, seven partial response, and two stable disease seen post NACT in this
      study. CONCLUSION: Docetaxel, cisplatin and 5 fluorouracil regimen can be
      routinely administered at our center with the supportive care methods and
      precautionary methods used in our study.

PMID- 24947101
TI  - ICON 2013: practical consensus recommendations for hormone receptor-positive Her2
      negative advanced or metastatic breastcancer.
AB  - The management of hormone receptor-positive Her2-negative breast cancer patients
      with advanced or metastatic disease is a common problem in India and other
      countries in this region. This expert group used data from published literature,
      practical experience, and opinion of a large group of academic oncologists, to
      arrive at practical consensus recommendations for use by the community
      oncologists. 

PMID- 24947102
TI  - Epidemiology, control and prevention of tobacco induced oral mucosal lesions in
      India.
AB  - Oral cancer is one of the leading causes of human morbidity and mortality
      especially in developing countries like India. Tobacco consumption in smokeless
      and smoking form along with alcohol is considered as the primary risk factors.
      Tobacco is a major health challenge with various tobacco products available for
      use which are known to have deleterious effects on the oral mucosa. The oral
      lesions caused by tobacco are inclusive of those that are less likely to progress
      to cancer; lesions with increased tendency to develop into cancer and cancerous
      lesions. Prevention and control of tobacco induced oral mucosal lesions is the
      prime requisite currently and mainly involves measures undertaken at primary,
      secondary and tertiary levels. Primary prevention plays a pivotal role in tobacco
      induced lesions and steps can be taken at policy level, community as well as
      individual level. This review paper focuses on the epidemiological data of
      tobacco induced oral mucosal lesions in India available in the literature with an
      overview on various strategies for their prevention and control. 

PMID- 24947103
TI  - Quality of life in head and neck cancer patients: a physiotherapist's
      perspective.

PMID- 24947105
TI  - Investment in early childhood development.

PMID- 24947104
TI  - Parallel transmit pulse design for patients with deep brain stimulation implants.
AB  - PURPOSE: Specific absorption rate (SAR) amplification around active implantable
      medical devices during diagnostic MRI procedures poses a potential risk for
      patient safety. In this study, we present a parallel transmit (pTx) strategy that
      can be used to safely scan patients with deep brain stimulation (DBS) implants.
      METHODS: We performed electromagnetic simulations at 3T using a uniform phantom
      and a multitissue realistic head model with a generic DBS implant. Our strategy
      is based on using implant-friendly modes, which are defined as the modes of an
      array that reduce the local SAR around the DBS lead tip. These modes are used in
      a spokes pulse design algorithm in order to produce highly uniform magnitude
      least-squares flip angle excitations. RESULTS: Local SAR (1 g) at the lead tip is
      reduced below 0.1 W/kg compared with 31.2 W/kg, which is obtained by a simple
      quadrature birdcage excitation without any sort of SAR mitigation. For the
      multitissue realistic head model, peak 10 g local SAR and global SAR are obtained
      as 4.52 W/kg and 0.48 W/kg, respectively. A uniform axial flip angle is also
      obtained (NRMSE <3%). CONCLUSION: Parallel transmit arrays can be used to
      generate implant-friendly modes and to reduce SAR around DBS implants while
      constraining peak local SAR and global SAR and maximizing flip angle homogeneity.

PMID- 24947106
TI  - Effect of integrated responsive stimulation and nutrition interventions in the
      Lady Health Worker programme in Pakistan on child development, growth, and health
      outcomes: a cluster-randomised factorial effectiveness trial.
AB  - BACKGROUND: Stimulation and nutrition delivered through health programmes at a
      large scale could potentially benefit more than 200 million young children
      worldwide who are not meeting their developmental potential. We investigated the
      feasibility and effectiveness of the integration of interventions to enhance
      child development and growth outcomes in the Lady Health Worker (LHW) programme
      in Sindh, Pakistan. METHODS: We implemented a community-based cluster-randomised
      effectiveness trial through the LHW programme in rural Sindh, Pakistan, with a 2
      * 2 factorial design. We randomly allocated 80 clusters (LHW catchments) of
      children to receive routine health and nutrition services (controls; n=368),
      nutrition education and multiple micronutrient powders (enhanced nutrition;
      n=364), responsive stimulation (responsive stimulation; n=383), or a combination
      of both enriched interventions (n=374). The allocation ratio was 1:20 (ie, 20
      clusters per intervention group). The data collection team were masked to the
      allocated intervention. All children born in the study area between April, 2009,
      and March, 2010, were eligible for enrolment if they were up to 2.5 months old
      without signs of severe impairments. Interventions were delivered by LHWs to
      families with children up to 24 months of age in routine monthly group sessions
      and home visits. The primary endpoints were child development at 12 and 24 months
      of age (assessed with the Bayley Scales of Infant and Toddler Development, Third
      Edition) and growth at 24 months of age. Analysis was by intention to treat. This
      trial is registered with ClinicalTrials.gov, number NCT007159636. FINDINGS: 1489
      mother-infant dyads were enrolled into the study, of whom 1411 (93%) were
      followed up until the children were 24 months old. Children who received
      responsive stimulation had significantly higher development scores on the
      cognitive, language, and motor scales at 12 and 24 months of age, and on the
      social-emotional scale at 12 months of age, than did those who did not receive
      the intervention. Children who received enhanced nutrition had significantly
      higher development scores on the cognitive, language, and social-emotional scales
      at 12 months of age than those who did not receive this intervention, but at 24
      months of age only the language scores remained significantly higher. We did not
      record any additive benefits when responsive stimulation was combined with
      nutrition interventions. Responsive stimulation effect sizes (Cohen's d) were 0.6
      for cognition, 0.7 for language, and 0.5 for motor development at 24 months of
      age; these effect sizes were slightly smaller for the combined intervention group
      and were low to moderate for the enhanced nutrition intervention alone. Children
      exposed to enhanced nutrition had significantly better height-for-age Z scores at
      6 months (p<0.0001) and 18 months (p=0.02) than did children not exposed to
      enhanced nutrition. Longitudinal analysis showed a small benefit to linear growth
      from enrolment to 24 months (p=0.026) in the children who received the enhanced
      nutrition intervention. INTERPRETATION: The responsive stimulation intervention
      can be delivered effectively by LHWs and positively affects development outcomes.
      The absence of a major effect of the enhanced nutrition intervention on growth
      shows the need for further analysis of mediating variables (eg, household food
      security status) that will help to optimise future nutrition implementation
      design. FUNDING: UNICEF.

PMID- 24947107
TI  - [Sleep and academic performance in young elite athletes].
AB  - RATIONALE: In French law (Code du Sport), the status of elite athlete is allowed
      for young athletes beginning at the age of 12 years. For these young athletes,
      the aim is to reach the highest level of performance in their sport without
      compromising academic performance. Training time is therefore often substantial
      and sleep patterns appear to play a key role in performance recovery. The aim of
      this study was to assess sleep patterns and their effects on academic performance
      in young elite athletes. MATERIAL AND METHODS: Sleep patterns were assessed using
      questionnaires completed during a specific information-based intervention on
      sports medicine topics. The academic performance of young elite athletes was
      assessed by collecting their grades (transmitted by their teachers). RESULTS:
      Sleep patterns were assessed for 137 young elite athletes (64 females, 73 males;
      mean age, 15.7 years) and academic performance for 109 of them. Daily sleep
      duration during school periods (8h22 +/- 38 min) were shorter compared to
      holidays and week-ends (10h02 +/- 1h16, P<0.0001). Fifty-six athletes (41 %)
      subjectively estimated their sleep quality as poor or just sufficient. Poor sleep
      quality was correlated with poor academic performance in this specific athlete
      population. DISCUSSION: Sleep is the most important period for recovery from
      daily activity, but little information is available regarding the specific
      population of young elite athletes. The results reported herein suggest
      insufficiency (quantitatively and qualitatively) of sleep patterns in some of the
      young athletes, possibly leading to detrimental effects on athletic performance.
      Moreover, disturbed sleep patterns may also impact academic performance in young
      elite athletes. CONCLUSION: Teachers, athletic trainers, physicians, and any
      other professionals working with young elite athletes should pay particular
      attention to this specific population regarding the possible negative
      repercussions of poor sleep patterns on academic and athletic performance.

PMID- 24947108
TI  - [Malnutrition screening increases the value of hospital care in children].

PMID- 24947109
TI  - [Endocarditis complicated by an aneurysm of the superior mesenteric artery].
AB  - Infective endocarditis (IE) is a rare, polymorphic disease in children. Mycotic
      aneurysm is a rare condition that complicates about 2.5 to 10% of cases of
      endocarditis. It is responsible for significant morbidity and mortality [1,2].
      Mycotic aneurysms are often asymptomatic, physical examination is poor, but the
      diagnosis should be considered with the triad including fever, abdominal pain,
      and abdominal mass beating. Abdominal ultrasound and computed tomography are the
      most useful for the identification of the aneurysmal mass. However, angiography
      is an interesting addition to confirm the diagnosis and implement a treatment
      procedure [3]. The treatment of SMA aneurysms is largely surgical. IE treatment
      is based on antibiotic therapy combined with surgical repair. We report the case
      of a 15-year-old patient, first operated for an SMA aneurysm complicating the
      course of IE, who secondarily underwent mitral valve repair. We review the
      epidemiology, diagnosis, and care principles of mycotic aneurysms of the SMA.

PMID- 24947110
TI  - [Viral epidemiology and clinical severity during the peak of the influenza
      A(H1N1) variant epidemic in febrile respiratory diseases of children].
AB  - In 2009, a new emerging flu virus, A(H1N1), was identified. Its true medical
      impact on children's health remains widely debated. AIM: To define the prevalence
      of respiratory disease in children hospitalized with fever during the influenza
      A(H1N1) epidemic and to determine the clinical, paraclinical, and outcome
      characteristics according to the viruses identified. MATERIAL AND METHODS:
      Children hospitalized for a febrile respiratory disease were included in this
      prospective cohort study conducted at Bordeaux University's Children's Hospital
      (France) during the influenza epidemic from 2009/11/23 to 2009/12/20. RESULTS:
      Seventy-three children were included in the study. Viruses were identified by PCR
      in 52% (38/73) of cases, including 23% (17/73) A(H1N1) virus and 29% (21/73)
      other viruses, 22% (16/73) of which were syncytial respiratory viruses. There was
      only one case of co-infection between A(H1N1) virus and another virus from the
      para-influenza virus or adenovirus or bocavirus pool. No significant difference
      regarding age, sex, or risk factors in the different viral groups was noted.
      Regarding the A(H1N1) virus, the most frequent symptoms were deterioration of the
      overall health status, cough, ENT disease, and rapid breathing, with
      significantly less increased breathing effort and auscultatory abnormality albeit
      with more seizures. There was no significant difference between groups regarding
      laboratory data. Management and outcome were similar. CONCLUSION: The prevalence
      of A(H1N1) virus during the 2009 epidemic in Aquitaine was low among febrile
      hospitalized children with breathing symptoms. Clinical and paraclinical signs
      were non-specific. The tolerance and prognosis of influenza A(H1N1) infection in
      children was satisfactory.

PMID- 24947111
TI  - [Evaluation of an obesity prevention program for school-aged children in deprived
      urban areas].
AB  - OBJECTIVE: Increasing prevalence of obesity particularly affects underprivileged
      families and children. This study aimed to estimate the efficiency of an obesity
      prevention program for school-aged children in deprived urban areas. METHODS:
      This was an intervention trial with a before-and-after comparison of a cohort of
      school-aged children in preschool and primary school in three deprived urban
      areas in Grenoble, France. All school-aged children in the first and third year
      of preschool and the third year of primary school during the 2008-2009 and 2009
      2010 school years, whose parents agreed to participate in the study, were
      included. Children were seen again 2 years later. The staff of the school health
      service measured and weighed the children during a medical check-up, thus
      determining their body mass index (BMI) and Z score. A school doctor suggested
      specific care to the parents of overweight children. A lifestyle questionnaire
      was completed. The primary outcome was changes in BMI and the Z score over 2
      years. The secondary outcome was changes in lifestyle and eating habits. RESULTS:
      A total of 2434 children were included in the screening campaign. Of the 2434
      children included in screening, 1824 children were reviewed and evaluated at 2
      years. At inclusion, overweight prevalence increased with age, from 6.4% in the
      first year of preschool to 21.9% in the third year of primary school. More than
      60% of overweight children had a high social vulnerability score. Prevalence of
      overweight increased from 13.8% to 21.5% in 2 years in the entire cohort
      (P<0.001). In the 252 overweight children, the mean BMI increased from 20 kg/m(2)
      to 21.8 kg/m(2) (P<0.001), as did the mean Z score, which increased from 2.72 to
      2.9 (P<0.001). There was no significant interaction depending on whether the
      family physician was in private practice or employed by a health center.
      According to their eating habits, fewer of the overweight children had a snack in
      the morning and more had a school lunch. More than half of the children thought
      they had improved their eating habits. They played more sports (30% versus
      49.5%). CONCLUSION: This study failed to demonstrate that incentive for medical
      management of excess weight had an effect on the short-term (2 years) evolution
      of the children's corpulence.

PMID- 24947112
TI  - Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2
      mutation carriers with a history of unilateral breast cancer: a prospective
      analysis.
AB  - Data on survival of BRCA1/2-associated primary breast cancer (PBC) patients who
      opt for subsequent contralateral risk-reducing mastectomy (CRRM) are scarce and
      inconsistent. We examined the efficacy of CRRM on overall survival in mutation
      carriers with a history of PBC. From a Dutch multicentre cohort, we selected 583
      BRCA-associated PBC patients, being diagnosed between 1980 and 2011. Over time,
      242 patients (42%) underwent CRRM and 341 patients (58%) remained under
      surveillance. Survival analyses were performed using Cox models, with CRRM as a
      time-dependent covariate. The median follow-up after PBC diagnosis was 11.4
      years. In the CRRM group, four patients developed contralateral breast cancer
      (2%), against 64 patients (19%) in the surveillance group (p < 0.001). The
      mortality was lower in the CRRM group than in the surveillance group (9.6 and
      21.6 per 1000 person-years of observation, respectively; adjusted hazard ratio
      0.49, 95% confidence interval 0.29-0.82). Survival benefit was especially seen in
      young PBC patients (<40 years), in patients having a PBC with differentiation
      grade 1/2 and/or no triple-negative phenotype, and in patients not treated with
      adjuvant chemotherapy. We conclude that CRRM is associated with improved overall
      survival in BRCA1/2 mutation carriers with a history of PBC. Further research is
      warranted to develop a model based on age at diagnosis and tumour and treatment
      characteristics that can predict survival benefit for specific subgroups of
      patients, aiming at further personalized counselling and improved decision
      making. 

PMID- 24947114
TI  - Effects of temperature and photoperiod on daily activity rhythms of Lutzomyia
      longipalpis (Diptera: Psychodidae).
AB  - BACKGROUND: Insect vectors have been established as models in Chronobiology for
      many decades, and recent studies have demonstrated a close relationship between
      the circadian clock machinery, daily rhythms of activity and vectorial capacity.
      Lutzomyia longipalpis, the primary vector of Leishmania (Leishmania) infantum in
      the New World, is reported to have crepuscular/nocturnal activity in the wild.
      However, most of these studies applied hourly CDC trap captures, which is a good
      indicative of L. longipalpis behaviour, but has limited accuracy due to the
      inability to record the daily activity of a single insect during consecutive
      days. In addition, very little is known about the activity pattern of L.
      longipalpis under seasonal variations of average temperature and day length in
      controlled laboratory conditions. METHODS: We recorded the locomotor activity of
      L. longipalpis males under different artificial regimes of temperature and
      photoperiod. First, in order to test the effects of temperature on the activity,
      sandflies were submitted to regimes of light/dark cycles similar to the equinox
      photoperiod (LD 12:12) combined with different constant temperatures (20 degrees
      C, 25 degrees C and 30 degrees C). In addition, we recorded sandfly locomotor
      activity under a mild constant temperature (25 degrees C with different day
      length regimes: 8 hours, 12 hours and 16 hours). RESULTS: L. longipalpis
      exhibited more activity at night, initiating dusk-related activity (onset time)
      at higher rather than lower temperatures. In parallel, changes of photoperiod
      affected anticipation as well as all the patterns of activity (onset, peak and
      offset time). However, under LD 16:08, sandflies presented the earliest values of
      maximum peak and offset times, contrary to other regimes. CONCLUSIONS: Herein, we
      showed that light and temperature modulate L. longipalpis behaviour under
      controlled laboratory conditions, suggesting that sandflies might use
      environmental information to sustain their crepuscular/nocturnal activity, as
      well as other important aspects as mating and host-seeking at appropriate times
      in different seasons. Our results depict previously unappreciated aspects of the
      L. longipalpis daily rhythms of activity that might have important
      epidemiological implications.

PMID- 24947113
TI  - Induction of cell cycle arrest and apoptosis in caspase-3 deficient MCF-7 cells
      by Dillenia suffruticosa root extract via multiple signalling pathways.
AB  - BACKGROUND: Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been
      reported to exhibit strong cytotoxicity towards breast cancer cells. The present
      study was designed to investigate the cell cycle profile, mode of cell death and
      signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast
      cancer cells. METHODS: Dillenia suffruticosa root was extracted by sequential
      solvent extraction. The anti-proliferative activity of DCM-DS was determined by
      using MTT assay. The mode of cell death was evaluated by using inverted light
      microscope and Annexin-V/PI-flow cytometry analysis. Cell cycle analysis and
      measurement of intracellular reactive oxygen species (ROS) were performed by
      using flow cytometry. MCF-7 cells were co-treated with antioxidants alpha
      tocopherol and ascorbic acid to evaluate whether the cell death was mainly due to
      oxidative stress. GeXP-based multiplex system was employed to investigate the
      expression of apoptotic, growth and survival genes in MCF-7 cells. Western blot
      analysis was performed to confirm the expression of the genes. RESULTS: DCM-DS
      was cytotoxic to the MCF-7 cells in a time-and dose-dependent manner. The IC50
      values of DCM-DS at 24, 48 and 72 hours were 20.3 +/- 2.8, 17.8 +/- 1.5 and 15.5
      +/- 0.5 MUg/mL, respectively. Cell cycle analysis revealed that DCM-DS induced
      G0/G1 and G2/M phase cell cycle arrest in MCF-7 cells at low concentration (12.5
      and 25 MUg/mL) and high concentration (50 MUg/mL), respectively. Although Annexin
      V/PI-flow cytometry analysis has confirmed that DCM-DS induced apoptosis in MCF-7
      cells, the distinct characteristics of apoptosis such as membrane blebbing,
      chromatin condensation, nuclear fragmentation and formation of apoptotic bodies
      were not observed under microscope. DCM-DS induced formation of ROS in MCF-7
      cells. Nevertheless, co-treatment with antioxidants did not attenuate the cell
      death at low concentration of DCM-DS. The pro-apoptotic gene JNK was up-regulated
      whereby anti-apoptotic genes AKT1 and ERK1/2 were down-regulated in a dose
      dependent manner. Western blot analysis has confirmed that DCM-DS significantly
      up-regulated the expression of pro-apoptotic JNK1, pJNK and down-regulated anti
      apoptotic AKT1, ERK1 in MCF-7 cells. CONCLUSION: DCM-DS induced cell cycle arrest
      and apoptosis in MCF-7 cells via multiple signalling pathways. It shows the
      potential of DCM-DS to be developed to target the cancer cells with mutant
      caspase-3.

PMID- 24947115
TI  - Three-dimensional visualization of termite (Apicotermitinae) enteric valve using
      confocal laser scanning microscopy.
AB  - Humivorous termites are dominant members of tropical rainforest soil communities.
      In the soil-feeding subfamily Apicotermitinae (Termitidae), the enteric valve
      connecting the first section of the hindgut to the paunch often displays a
      complex sclerotized armature everted towards the lumen of the paunch. This
      structure is central in termite taxonomy but its function remains hypothetical.
      Here, we evaluate the potential of confocal laser scanning microscopy to provide
      detailed imaging of the valve of Anoplotermes parvus, by comparison with bright
      field microscopy and scanning electron microscopy. We detected a strong far-red
      emission of the enteric valve armature that sharply contrasted with the
      surrounding tissues, providing a convenient method to highlight minute structural
      elements of the valve and its three-dimensional structure. The method is easy to
      use and is applicable to standard archival material as demonstrated by images of
      enteric valves of four other Apicotermitinae species. It may represent a valuable
      asset for the study of termite enteric valves, for the purpose of taxonomy or
      functional morphology. 

PMID- 24947116
TI  - Traumatic subarachnoid hemorrhage due to motor vehicle crash versus fall from
      height: a 4-year epidemiologic study.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a common cause of morbidity and
      mortality worldwide. It is difficult to estimate the real incidence of traumatic
      subarachnoid hemorrhage (TSAH). Although TSAH after trauma is associated with
      poor prognoses, the impact of mechanism of injury (MOI) and the pathophysiology
      remains unknown. We hypothesized that outcome of TSAH caused by motor vehicle
      crash (MVC) or fall from height (FFH) varies based on the MOI. METHODS: Data were
      collected retrospectively from a prospectively created database registry in the
      section of Trauma Surgery at Hamad General Hospital between January 2008 and July
      2012. All patients presented with head trauma and TSAH were included. Patient
      data included age, gender, nationality, mechanism of injury, injury severity
      score (ISS), types of head injuries, and associated injuries. Ventilator days,
      intensive care unit length of stay, pneumonia, and mortality were also studied.
      RESULTS: A total of 1665 patients with TBI were identified, of them 403 had TSAH
      with a mean age of 35 +/- 15 years. Of them 93% were male patients and 86% were
      expatriates. MVC (53%) and FFH (35%) were the major mechanisms of injury. The
      overall mean ISS and head abbreviated injury score were 19 +/- 10.6 and 3.4 +/-
      0.96, respectively. Patients in MVC group sustained severe TSAH, had
      significantly greater head abbreviated injury score (3.5 +/- 0.9 vs. 3.2 +/- 0.9;
      P = 0.009) and ISS (21.6 +/- 10.6 vs. 15.9 +/- 9.5; P = 0.001), and lower scene
      Glasgow coma scale (10.8 +/- 4.8 vs. 13.2 +/- 3.4; P = 0.001) compared with the
      FFH group. In addition, the MVC group sustained more intraventricular hemorrhage
      (4.7 vs. 0.7; P = 0.001) and diffuse axonal injury (4.2 vs. 2.9; P = 0.001). In
      contrast, extradural hemorrhage (14.3% vs. 11.6%; P = 0.008) was higher in the
      FFH group. Lower extremities (14% vs. 4.3%; P = 0.004) injury was mainly
      associated with the MVC group. The overall mortality was 19 % among patients with
      TSAH. The mortality rate was higher in the MVC group when compared with the FFH
      group (24% vs. 10%; P = 0.001). In both groups, ISS and Glasgow coma scale at the
      scene were independent predictors of mortality. CONCLUSIONS: Patients with TSAH
      have a higher mortality rate. In this population, MVCs are associated with a 3
      fold increased risk of mortality. Therefore, prevention of MVC and fall can
      reduce the incidence and severity of TBI in Qatar.

PMID- 24947117
TI  - The implementation and efficacy of the Northwestern High Risk Spine Protocol.
AB  - OBJECTIVE: The aims of this study were to determine the efficacy and feasibility
      of implementation of the intraoperative component of a high risk spine (HRS)
      protocol for improving perioperative patient safety in complex spine fusion
      surgery. METHODS: In this paired availability study, the total number of red
      blood cell units transfused was used as a surrogate marker for our management
      protocol efficacy, and the number of protocol violations was used as a surrogate
      marker for protocol compliance. RESULTS: The 548 patients (284 traditional vs.
      264 HRS protocol) were comparable in all demographics, coexisting diseases,
      preoperative medications, type of surgery, and number of posterior levels
      instrumented. However, the surgical duration was 70 minutes shorter in the new
      group (range, 32-108 minutes shorter; P < 0.0001) and the new protocol patients
      received a median of 1.1 units less of total red blood cell units (range, 0-2.4
      units less; P = 0.006). There were only 7 (2.6%) protocol violations in the new
      protocol group. CONCLUSIONS: The intraoperative component of the HRS protocol,
      based on two Do-Confirm checklists that focused on 1) organized communication
      between intraoperative team members and 2) active maintenance of oxygen delivery
      and hemostasis appears to maintain a safe intraoperative environment and was
      readily implemented during a 3-year period.

PMID- 24947118
TI  - Management of deep arteriovenous malformations.

PMID- 24947119
TI  - Approaches to upper basilar artery aneurysms.

PMID- 24947120
TI  - How good? Better. How simple? Simpler. And testable to boot.

PMID- 24947121
TI  - Evaluation of an every-other-day palonosetron schedule to control emesis in
      multiple-day high-dose chemotherapy.
AB  - AIM: Efficacy of intermittent palonosetron dosing in patients undergoing multiple
      day, high-dose chemotherapy (HDC) was investigated. PATIENTS & METHODS: Fifty
      eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day
      plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was
      complete control (CC; no emesis, no rescue anti-emetics, and no more than mild
      nausea) in the overall acute-period (until 24 h after chemotherapy completion).
      RESULTS: Acute-period CC occurred in 81% and 50% of patients receiving
      palonosetron and ondansetron (historical control cohort), respectively.
      Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC
      regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic
      outcome. CONCLUSION: Palonosetron every other day plus daily dexamethasone is an
      effective anti-emetic coverage in patients undergoing HDC.

PMID- 24947122
TI  - In vitro evaluation of ice-cold saline irrigation during catheter radiofrequency
      ablation.
AB  - INTRODUCTION: Irrigated radiofrequency (RF) catheters allow tissue-electrode
      interface cooling, decreasing thrombus risk while enabling higher RF power
      delivery. The impact of irrigation with ice-cold saline (ICS) instead of
      conventional ambient-temperature saline (ATS) on lesion formation is unknown.
      METHODS AND RESULTS: We performed 120 RF ablations in vitro on porcine left
      ventricles, using ICS (<5  degrees C) or ATS (21  degrees C) irrigation. For ICS
      irrigation, the irrigation circuit was cooled externally to maintain delivery of
      cooled saline at the catheter's tip. We applied 20 g of contact force, and
      delivered 20 W (irrigation 8 or 17 mL/min) or 30 W (irrigation 17 or 30 mL/min)
      RF power. Temperatures at tissue-electrode interface and 3-mm depth were assessed
      by fluoroptic probes. Lesion dimensions were assessed. ICS irrigation cooled the
      tissue-electrode interface better than ATS (53.9 +/- 9.6  degrees C vs. 63 +/-
      11.4  degrees C, P < 0.001). Temperatures at 3-mm depth were similar at 30 W
      using ICS and ATS (104.2 +/- 9.3  degrees C vs. 105.8 +/- 7.3  degrees C, P =
      0.5), but were cooler at 20 W using ICS (71.3 +/- 11.6  degrees C vs. 100.2 +/-
      11.9  degrees C, P < 0.001). This translated into smaller lesions at 20 W with
      ICS versus ATS. At 30 W with 17 mL/min flow rate, lesions had the same depth with
      ICS and ATS (4.9 +/- 0.8 mm vs. 5.4 +/- 0.7 mm, P = 0.13) but were narrower with
      ICS (7.7 +/- 0.8 mm vs. 9.3 +/- 1.2 mm, P = 0.001). At 30 mL/min, lesions had the
      same dimensions. Steam pop rate was similar using ICS or ATS irrigation.
      CONCLUSION: ICS irrigation more effectively cools tissue-electrode interface than
      ATS. This may improve RF safety by potentially decreasing thrombus formation,
      thus facilitating safe ablation at a low saline volume load. However at lower RF
      power, ICS reduced lesion size compared to ATS.

PMID- 24947123
TI  - Traumatic insertion of eyelashes into corneal stroma.
AB  - An unusual case of eyelashes being traumatically inserted into the corneal stroma
      is presented. A 75-year-old hit her right eye with her own fist, presenting with
      intra-corneal eyelashes. All remained entirely within the cornea, with no breach
      of the endothelium. They seemed to have tracked there first through the superior
      conjunctiva and then the superior limbus. The lashes were surgically removed,
      with good visual recovery. The authors present a short review of intra-ocular
      eyelash insertion. 

PMID- 24947125
TI  - Multiple testing in big data.

PMID- 24947124
TI  - Folding-upon-binding and signal-on electrochemical DNA sensor with high affinity
      and specificity.
AB  - Here we investigate a novel signal-on electrochemical DNA sensor based on the use
      of a clamp-like DNA probe that binds a complementary target sequence through two
      distinct and sequential events, which lead to the formation of a triplex DNA
      structure. We demonstrate that this target-binding mechanism can improve both the
      affinity and specificity of recognition as opposed to classic probes solely based
      on Watson-Crick recognition. By using electrochemical signaling to report the
      conformational change, we demonstrate a signal-on E-DNA sensor with up to 400%
      signal gain upon target binding. Moreover, we were able to detect with nanomolar
      affinity a perfectly matched target as short as 10 bases (K(D) = 0.39 nM).
      Finally, thanks to the molecular "double-check" provided by the concomitant
      Watson-Crick and Hoogsteen base pairings involved in target recognition, our
      sensor provides excellent discrimination efficiency toward a single-base
      mismatched target.

PMID- 24947126
TI  - Fruit and vegetable intake and risk of wheezing and asthma: a systematic review
      and meta-analysis.
AB  - Major bibliographic databases were searched for studies examining the
      relationship between fruit and vegetable consumption and the risk of wheezing and
      asthma. Random-effects models were used to pool study results. Subgroup analyses
      were conducted by fruit and vegetable categories, study design, and age group.
      Twelve cohorts, 4 population-based case-control studies, and 26 cross-sectional
      studies published between January 1990 and July 2013 were identified. For the
      meta-analysis of adults and children, the relative risk (RR) and confidence
      intervals (CI) when comparing the highest intake group with the lowest intake
      group were 0.78 (95%CI, 0.70-0.87) for fruit and 0.86 (95%CI, 0.75-0.98) for
      vegetables. High intake of fruit and vegetables (RR = 0.76; 95%CI, 0.68-0.86 and
      RR = 0.83; 95%CI, 0.72-0.96) reduced the risk of childhood wheezing. Total intake
      of fruit and vegetables had a negative association with risk of asthma in adults
      and children (RR = 0.54; 95%CI, 0.41-0.69). Consuming fruit and vegetables during
      pregnancy had no association with the risk of asthma in offspring. High intake of
      fruit and vegetables may reduce the risk of asthma and wheezing in adults and
      children.

PMID- 24947127
TI  - Risk assessment of butyltins based on a fugacity-based food web bioaccumulation
      model in the Jincheng Bay mariculture area: II. Risk assessment.
AB  - A fugacity-based food web bioaccumulation model was constructed, and the biotic
      concentrations of butyltins in the food web of the Jincheng Bay mariculture area
      were estimated accordingly, using the water and sediment concentrations described
      in the accompanying paper (Part I). This paper presents an ecological risk
      assessment (ERA) and a human health risk assessment (HHRA) of the butyltins,
      based on the estimated tissue residues in the marine life in this area. The
      results showed that the ecological risk probability was greater than 0.05. At
      this level, management control is critical since sensitive marine species would
      be profoundly endangered by butyltin contamination. Few if any detrimental
      effects, however, would be generated for humans from exposure to butyltins
      through seafood consumption. The fugacity-based model can refine the ERA and HHRA
      of pollutants in marine areas, provide a basis for protecting marine ecology and
      the security of fishery products, and thus help determine the feasibility of a
      proposed aquaculture project.

PMID- 24947130
TI  - Outcomes of critical congenital heart disease requiring emergent neonatal cardiac
      intervention.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes for neonates with
      critical congenital heart disease (CHD) requiring emergent neonatal cardiac
      intervention (ENCI). METHODS: Neonates < 30 days of age that underwent ENCI at
      <48 h of age were retrospectively enrolled over a 2-year period. RESULTS: Forty
      seven neonates met inclusion criteria for ENCI comprising nine cardiac defects
      that underwent 25 catheterizations and 22 cardiothoracic surgeries. The main
      groups were d-transposition of the great arteries (DTGA) and total anomalous
      pulmonary venous return (TAPVR). Prenatal detection was 38% overall: higher for
      single ventricle (86%) and heterotaxy (75%) than for DTGA (28%) or TAPVR (13%).
      Mortality was 11.1% (2/18) in prenatally diagnosed versus 13.8% (4/29) in
      postnatally diagnosed neonates (p = 0.86). Prenatal detection was associated with
      shorter mean hospital stay: 16.8 versus 30.3 days (p = 0.03). Prenatally
      diagnosed patients had lower preoperative inotropic scores (p = 0.02), less
      acidosis (pH; p = 0.09), but decreased likelihood of spontaneous labor (p =
      0.01), lower gestational age (p = 0.01), and lower birth weight (p = 0.01).
      CONCLUSIONS: Fewer deaths occurred in neonates with prenatal detection of their
      critical CHD requiring ENCI. However, there was no statistical difference in
      survival demonstrated for prenatally diagnosed neonates in this small cohort.
      Prenatal detection did improve preoperative clinical status and shorten hospital
      length of stay.

PMID- 24947131
TI  - Type-tunable amplified spontaneous emission from core-seeded CdSe/CdS nanorods
      controlled by exciton-exciton interaction.
AB  - Type-tunable optical gain performance of core-seeded CdSe/CdS nanorods is studied
      via two-photon optical pumping. Controlling the exciton-exciton interaction by
      varying the core and shell size, blue-shifted and red-shifted modes of amplified
      spontaneous emission are systematically demonstrated and their type attributions
      are verified by time-resolved emission kinetics. 

PMID- 24947132
TI  - Two modes of photoinduced twisted intramolecular charge transfer in meso
      arylaminated subporphyrins.
AB  - Photoinduced twisted intramolecular charge transfer (TICT) of meso-(4
      dimethylamino)phenylamino subporphyrin and meso-(4-nitro)phenylamino subporphyrin
      has been revealed by steady-state and time-resolved absorption/fluorescence
      experiments and quantum calculations. Subporphyrins and undergo molecular
      twisting at the Cmeso-N bond and the N-Cipso bond, respectively, to trigger
      intramolecular charge separation, which is restricted at low temperature or in
      viscous paraffin oil with concurrent fluorescence recovery of local excited
      states. 

PMID- 24947133
TI  - A nanomedicine approach to effectively inhibit contracture during bladder
      acellular matrix allograft-induced bladder regeneration by sustained delivery of
      vascular endothelial growth factor.
AB  - Macroscopic evidence of contracture has been identified as a major issue during
      the regeneration process. We hypothesize that lack of angiogenesis is the primary
      cause of contracture and explore a nanomedicine approach to achieve sustained
      release of vascular endothelial growth factor (VEGF) to stimulate angiogenesis.
      We evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA) nanoparticles
      (NPs) for long-term (3 months) sustained release of VEGF in bladder acellular
      matrix allografts (BAMA) in a swine model. We anticipate that the sustained
      release of VEGF could stimulate angiogenesis along the regeneration process and
      thereby inhibit contracture. Bladder was replaced with BAMA (5*5 cm), modified
      with PLGA NPs encapsulated with VEGF in a pig model. The time points chosen for
      sampling were 1, 2, 4, and 12 weeks. The regenerated areas were then measured to
      obtain the contracture rate, and the extent of revascularization was calculated
      using histological and morphological features. In the control group of animals,
      the bladder was replaced with only BAMA. The in vivo release of VEGF was evident
      for ~3 months, achieving the goal of long-acting sustained release, and
      successfully promoted the regeneration of blood vessels and smooth muscle fibers.
      In addition, less collagen deposition was observed in the experimental group
      compared with control. Most importantly, the inhibition of contracture was highly
      significant, and the ultimate contracture rate decreased by ~57% in the
      experimental group compared with control. In isolated strips analysis, there were
      no significant differences between BAMA-regenerated (either VEGF added or not)
      and autogenous bladder. BAMA modified with VEGF-loaded PLGA-NPs can sustainably
      release VEGF in vivo (>3 months) to stimulate angiogenesis leading to the
      inhibition of contracture. This is the first study to report a viable
      nanomedicine-based strategy to overcome contracture during bladder regeneration
      induced by BAMA. Furthermore, this study also confirms that insufficient
      angiogenesis plays a crucial role in the onset of contracture. 

PMID- 24947134
TI  - Development of a quality of life instrument for children with advanced cancer:
      the pediatric advanced care quality of life scale (PAC-QoL).
AB  - BACKGROUND: There is currently no published, validated measures available that
      comprehensively capture quality of life (QoL) symptoms for children with poor
      prognosis malignancies. The pediatric advanced care-quality of life scale (PAC
      QoL) has been developed to address this gap. The current paper describes the
      first two phases in the development of this measure. PROCEDURES: The first two
      phases included: (1) construct and item generation, and (2) preliminary content
      validation. Domains of QoL relevant to this population were identified from the
      literature and items generated to capture each; items were then adapted to create
      versions sensitive to age/developmental differences. Two types of experts
      reviewed the draft PAC-QoL and rated items for relevance, understandability, and
      sensitivity of wording: bereaved parents (n = 8) and health care professionals
      (HCP; n = 7). Content validity was calculated using the index of content validity
      (CVI [Lynn. Nurs Res 1986;35:382-385]). RESULTS: One hundred and forty-one
      candidate items congruent with the domains identified as relevant to children
      with advanced malignancies were generated, and four report versions with a 5
      choice response scale created. Parent mean scores for importance,
      understandability, and sensitivity of wording ranged from 4.29 (SD = 0.52) to
      4.66 (SD = 0.50). The CVI ranged from 95% to 100%. These steps resulted in
      reductions of the PAC-QoL to 57-65 items, as well as a modification of the
      response scale to a 4-choice option with new anchors. CONCLUSIONS: The next phase
      of this study will be to conduct cognitive probing with the intended population
      to further modify and reduce candidate items prior to psychometric evaluation.

PMID- 24947135
TI  - Structural and functional characterization of ochratoxinase, a novel mycotoxin
      degrading enzyme.
AB  - Ochratoxin, with ochratoxin A as the dominant form, is one of the five major
      mycotoxins most harmful to humans and animals. It is produced by Aspergillus and
      Penicillium species and occurs in a wide range of agricultural products.
      Detoxification of contaminated food is a challenging health issue. In the present
      paper we report the identification, characterization and crystal structure (at
      2.2 A) of a novel microbial ochratoxinase from Aspergillus niger. A putative
      amidase gene encoding a 480 amino acid polypeptide was cloned and homologously
      expressed in A. niger. The recombinant protein is N-terminally truncated,
      thermostable, has optimal activity at pH ~6 and 66 degrees C, and is more
      efficient in ochratoxin A hydrolysis than carboxypeptidase A and Y, the two
      previously known enzymes capable of degrading this mycotoxin. The subunit of the
      homo-octameric enzyme folds into a two-domain structure characteristic of a metal
      dependent amidohydrolase, with a twisted TIM (triosephosphateisomerase)-barrel
      and a smaller beta-sandwich domain. The active site contains an aspartate residue
      for acid-base catalysis, and a carboxylated lysine and four histidine residues
      for binding of a binuclear metal centre. 

PMID- 24947136
TI  - Pro-healing effects of bilirubin in open excision wound model in rats.
AB  - Bilirubin, a by-product of heme degradation, has an important role in cellular
      protection. Therefore, we speculated that bilirubin could be of potential
      therapeutic value in wound healing. To validate the hypothesis, we used a full
      thickness cutaneous wound model in rats. Bilirubin (30 mg/kg) was administered
      intraperitoneally every day for 9 days. The surface area of the wound was
      measured on days 0, 2, 4, 7 and 10 after the creation of the wound. The
      granulation tissue was collected on day 10 post-wounding for analysing various
      parameters of wound healing. Bilirubin treatment accelerated wound contraction
      and increased hydroxyproline and glucosamine contents. mRNA expression of pro
      inflammatory factors such as intercellular cell adhesion molecule-1 (ICAM-1) and
      tumour necrosis factor-alpha (TNF-alpha) were down-regulated and that of anti
      inflammatory cytokine interleukin-10 (IL-10) was up-regulated. The findings
      suggest that bilirubin could be a new agent for enhancing cutaneous wound
      healing. 

PMID- 24947137
TI  - Mechanisms of physiological adjustment of N2 fixation in Cicer arietinum L.
      (chickpea) during early stages of water deficit: single or multi-factor controls.
AB  - Drought negatively impacts symbiotic nitrogen fixation (SNF) in Cicer arietinum
      L. (chickpea), thereby limiting yield potential. Understanding how drought
      affects chickpea nodulation will enable the development of strategies to
      biotechnologically engineer chickpea varieties with enhanced SNF under drought
      conditions. By analyzing carbon and nitrogen metabolism, we studied the
      mechanisms of physiological adjustment of nitrogen fixation in chickpea plants
      nodulated with Mesorhizobium ciceri during both drought stress and subsequent
      recovery. The nitrogenase activity, levels of several key carbon (in nodules) and
      nitrogen (in both nodules and leaves) metabolites and antioxidant compounds, as
      well as the activity of related nodule enzymes were examined in M. ciceri
      inoculated chickpea plants under early drought stress and subsequent recovery.
      Results indicated that drought reduced nitrogenase activity, and that this was
      associated with a reduced expression of the nifK gene. Furthermore, drought
      stress promoted an accumulation of amino acids, mainly asparagine in nodules (but
      not in leaves), and caused a cell redox imbalance in nodules. An accumulation of
      organic acids, especially malate, in nodules, which coincided with the decline of
      nodulated root respiration, was also observed under drought stress. Taken
      together, our findings indicate that reduced nitrogenase activity occurring at
      early stages of drought stress involves, at least, the inhibition of respiration,
      nitrogen accumulation and an imbalance in cell redox status in nodules. The
      results of this study demonstrate the potential that the genetic engineering
      based improvement of SNF efficiency could be applied to reduce the impact of
      drought on the productivity of chickpea, and perhaps other legume crops. 

PMID- 24947138
TI  - Automated identification of cell-type-specific genes in the mouse brain by image
      computing of expression patterns.
AB  - BACKGROUND: Differential gene expression patterns in cells of the mammalian brain
      result in the morphological, connectional, and functional diversity of cells. A
      wide variety of studies have shown that certain genes are expressed only in
      specific cell-types. Analysis of cell-type-specific gene expression patterns can
      provide insights into the relationship between genes, connectivity, brain
      regions, and cell-types. However, automated methods for identifying cell-type
      specific genes are lacking to date. RESULTS: Here, we describe a set of
      computational methods for identifying cell-type-specific genes in the mouse brain
      by automated image computing of in situ hybridization (ISH) expression patterns.
      We applied invariant image feature descriptors to capture local gene expression
      information from cellular-resolution ISH images. We then built image-level
      representations by applying vector quantization on the image descriptors. We
      employed regularized learning methods for classifying genes specifically
      expressed in different brain cell-types. These methods can also rank image
      features based on their discriminative power. We used a data set of 2,872 genes
      from the Allen Brain Atlas in the experiments. Results showed that our methods
      are predictive of cell-type-specificity of genes. Our classifiers achieved AUC
      values of approximately 87% when the enrichment level is set to 20. In addition,
      we showed that the highly-ranked image features captured the relationship between
      cell-types. CONCLUSIONS: Overall, our results showed that automated image
      computing methods could potentially be used to identify cell-type-specific genes
      in the mouse brain.

PMID- 24947139
TI  - Docetaxel rechallenge after an initial good response in patients with metastatic
      castration-resistant prostate cancer.
AB  - OBJECTIVE: To evaluate the benefit of docetaxel rechallenge in patients with
      metastatic castration-resistant prostate cancer (mCRPC) relapsing after an
      initial good response to first-line docetaxel. PATIENTS AND METHODS: We
      retrospectively reviewed the records of consecutive patients with mCRPC with a
      good response to first-line docetaxel [serum prostate specific antigen (PSA)
      decrease >=50%; no clinical/radiological progression]. We analysed the impact of
      management at relapse (docetaxel rechallenge or non-taxane-based therapy) on PSA
      response, symptomatic response (performance status/pain/analgesic consumption),
      and overall survival (OS). We used multivariate stepwise logistic regression to
      analyse potential predictors of a favourable outcome. RESULTS: We identified 270
      good responders to first-line docetaxel. The median progression-free interval
      (PFI) was 6 months from the last docetaxel dose. At relapse, 223 patients were
      rechallenged with docetaxel (82.5%) and 47 received non-taxane-based therapy.
      There was no significant difference in median OS {18.2 [95% confidence interval
      (CI) 16.1-22.00] and 16.8 [95%CI 13.4-21.5] months, respectively, P = 0.35}.
      However, good PSA response and symptom relief/stable disease were more frequent
      on docetaxel rechallenge (40.4% vs 10.6%, P < 0.001 for PSA). A PFI of >6 months
      and added estramustine predicted a good PSA response and symptomatic response on
      docetaxel rechallenge but only a PFI of >6 months predicted longer OS.
      Haemoglobin (<13 g/dL) and pain were associated with reduced OS. Docetaxel
      rechallenge increased the incidence of grade >=3 sensory neuropathy, nail
      disorders and asthenia/fatigue. CONCLUSIONS: Docetaxel rechallenge is a
      management option for responders to docetaxel with a PFI of >6 months, but did
      not prolong survival. Potential benefits should be weighed against the risk of
      cumulative toxicity.

PMID- 24947140
TI  - Dual functionalization of porous aromatic frameworks as a new platform for
      heterogeneous cascade catalysis.
AB  - Dual functionalization of porous aromatic frameworks (PAFs) has been illustrated
      in the context of incorporating two antagonistic sites of strong acid and strong
      base into the highly porous and highly robust PAF-1 via stepwise post-synthetic
      modification. The resulting bifunctionalized PAF-1 exhibits excellent
      performances in catalyzing a series of cascade reactions and demonstrates
      superior chemical stability compared to the counterparts of mesoporous silica and
      MOFs, thereby opening the door for dual functionalization of PAFs as a new
      platform for heterogeneous cascade catalysis. 

PMID- 24947142
TI  - Bimodal magmatism produced by progressively inhibited crustal assimilation.
AB  - The origin of bimodal (mafic-felsic) rock suites is a fundamental question in
      volcanology. Here we use major and trace elements, high-resolution Sr, Nd and Pb
      isotope analyses, experimental petrology and thermodynamic modelling to
      investigate bimodal magmatism at the iconic Carlingford Igneous Centre, Ireland.
      We show that early microgranites are the result of extensive assimilation of
      trace element-enriched partial melts of local metasiltstones into mafic parent
      magmas. Melting experiments reveal the crust is very fusible, but thermodynamic
      modelling indicates repeated heating events rapidly lower its melt-production
      capacity. Granite generation ceased once enriched partial melts could no longer
      form and subsequent magmatism incorporated less fertile restite compositions
      only, producing mafic intrusions and a pronounced compositional gap. Considering
      the frequency of bimodal magma suites in the North Atlantic Igneous Province, and
      the ubiquity of suitable crustal compositions, we propose 'progressively
      inhibited crustal assimilation' (PICA) as a major cause of bimodality in
      continental volcanism. 

PMID- 24947141
TI  - Atomic force microscopy based nanoassay: a new method to study alpha-Synuclein
      dopamine bioaffinity interactions.
AB  - Intrinsically Disordered Proteins (IDPs) are characterized by the lack of well
      defined 3-D structure and show high conformational plasticity. For this reason,
      they are a strong challenge for the traditional characterization of structure,
      supramolecular assembly and biorecognition phenomena. We show here how the fine
      tuning of protein orientation on a surface turns useful in the reliable testing
      of biorecognition interactions of IDPs, in particular alpha-Synuclein. We
      exploited atomic force microscopy (AFM) for the selective, nanoscale confinement
      of alpha-Synuclein on gold to study the early stages of alpha-Synuclein
      aggregation and the effect of small molecules, like dopamine, on the aggregation
      process. Capitalizing on the high sensitivity of AFM topographic height
      measurements we determined, for the first time in the literature, the
      dissociation constant of dopamine-alpha-Synuclein adducts. 

PMID- 24947143
TI  - Novel prognostic markers revealed by a proteomic approach separating benign from
      malignant insulinomas.
AB  - The prognosis of pancreatic neuroendocrine tumors is related to size, histology
      and proliferation rate. However, this stratification needs to be refined further.
      We conducted a proteome study on insulinomas, a well-defined pancreatic
      neuroendocrine tumor entity, in order to identify proteins that can be used as
      biomarkers for malignancy. Based on a long follow-up, insulinomas were divided
      into those with metastases (malignant) and those without (benign). Microdissected
      cells from six benign and six malignant insulinomas were subjected to a procedure
      combining fluorescence dye saturation labeling with high-resolution two
      dimensional gel electrophoresis. Differentially expressed proteins were
      identified using nano liquid chromatography-electrospray ionization/multi-stage
      mass spectrometry and validated by immunohistochemistry on tissue microarrays
      containing 62 insulinomas. Sixteen differentially regulated proteins were
      identified among 3000 protein spots. Immunohistochemical validation revealed that
      aldehyde dehydrogenase 1A1 and voltage-dependent anion-selective channel protein
      1 showed significantly stronger expression in malignant insulinomas than in
      benign insulinomas, whereas tumor protein D52 (TPD52) binding protein was
      expressed less strongly in malignant insulinomas than in benign insulinomas.
      Using multivariate analysis, low TPD52 expression was identified as a strong
      independent prognostic factor for both recurrence-free and overall disease
      related survival. 

PMID- 24947146
TI  - Authorship issues: grizzles, guests and ghosts.

PMID- 24947145
TI  - Recurrence and progression in patients with non-muscle invasive bladder cancer:
      prognostic models including multicolor fluorescence in situ hybridization
      molecular grading.
AB  - OBJECTIVE: To test the prognostic value of multicolor fluorescence in situ
      hybridization analyses of tumor cells in urine for prediction of the recurrence
      and progression of tumor in patients with intermediate risk non-muscle invasive
      bladder cancer. METHODS: A total of 168 patients with non-muscle invasive bladder
      cancer were included in the study. Fluorescence in situ hybridization was carried
      out on the bladder wash urine collected before resection. Tumors were classified
      as low molecular grading if they had a diploid chromosomal pattern or only a loss
      of p16 or ch3 aneuploidy, and as high molecular grading if they showed aneuploidy
      of ch7 or 17. Cox regression models assessed the added prognostic value of
      fluorescence in situ hybridization for primary tumor recurrence or progression,
      respectively. RESULTS: Median follow up was 67 months. A total of 57% of tumors
      were classified as low molecular grading. The 2- and 5-year recurrence-free
      survival was 68% and 49% for low molecular grading, and 47% and 30% for high
      molecular grading, respectively. The 2- and 5-year progression-free survival was
      95% and 84% for low molecular grading, and 79% and 58% for high molecular grading
      tumor patients, respectively. Molecular grading (hazard ratio 1.60; P = 0.03) was
      associated with recurrence, when also accounting for histopathology and a
      patient's characteristics. Both cancer severity score (hazard ratio 1.51; P <
      0.01) and molecular grading (hazard ratio 2.53; P < 0.01) independently and
      positively predicted progression in multivariable models. The C-index for
      predicting recurrence increased from 0.58 to 0.61 when molecular grading
      fluorescence in situ hybridization was included in the model, and from 0.68 to
      0.72 when predicting progression. CONCLUSIONS: Fluorescence in situ hybridization
      based molecular grading increases the accuracy of a prognostic model, predicting
      both recurrence and progression in patients with intermediate risk non-muscle
      invasive bladder cancer.

PMID- 24947144
TI  - CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family
      transcription factor expression.
AB  - Recent molecular advances have identified a novel, clinically aggressive subgroup
      of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion
      of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX
      sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high
      grade nuclear features, including vesicular chromatin and nucleoli, patchy clear
      cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases,
      including 6 newly identified cases, 2 with paired metastases. Given our prior
      observation of trisomy 8 in these tumors, we assayed for amplification and
      expression of MYC (c-Myc) and representative downstream targets. Trisomy 8 was
      detected in 5/7 testable cases, with further amplification of MYC locus in 6/7
      testable cases and immunohistochemical expression of MYC in 10/10. The canonical
      MYC transcriptional target, p21, but not MTDH, was differentially expressed
      compared with Ewing sarcomas. Given prior observation of induction of ETS-family
      transcription factors by the fusion oncoprotein, we assayed and identified highly
      prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary
      regarding use of these immunostains in prospective case workup, whereas the
      prevalent MYC amplification may represent a therapeutically targetable oncogenic
      pathway in CIC-DUX sarcomas. 

PMID- 24947147
TI  - Chronic urticaria: an orphan disease for 125 years.

PMID- 24947148
TI  - Demodex and skin disease - false creation or palpable form?

PMID- 24947149
TI  - Type VII collagen and squamous cell carcinoma.

PMID- 24947150
TI  - Mycosis fungoides: promoter hypermethylation predicts disease progression.

PMID- 24947151
TI  - Mortality of bullous pemphigoid in Asia: the same as in Europe?

PMID- 24947152
TI  - Laser-assisted drug delivery: beyond ablative devices.

PMID- 24947159
TI  - Descending controls modulate inflammatory joint pain and regulate CXC chemokine
      and iNOS expression in the dorsal horn.
AB  - BACKGROUND: Descending control of nociceptive processing, by pathways originating
      in the rostral ventromedial medulla (RVM) and terminating in the dorsal horn,
      contributes to behavioural hypersensitivity in a number of pain models. Two
      facilitatory pathways have been identified and are characterized by serotonin (5
      HT) content or expression of the mu opiate receptor. Here we investigated the
      contribution of these pathways to inflammatory joint pain behaviour and gene
      expression changes in the dorsal horn. RESULTS: Selective lesion of the
      descending serotonergic (5-HT) pathway by prior intrathecal administration of 5,7
      dihydroxytryptamine attenuated hypersensitivity at early time points following
      ankle injection of CFA. In a separate study ablation of the mu opioid receptor
      expressing (MOR+) cells of the RVM, by microinjection of the toxin dermorphin
      saporin, resulted in a more prolonged attenuation of hypersensitivity post CFA.
      Microarray analysis was carried out to identify changes in dorsal horn gene
      expression associated with descending facilitation by the MOR+ pathway at 7d post
      joint inflammation. This analysis led to the identification of a number of genes
      including the chemokines Cxcl9 and Cxcl10, their common receptor Cxcr3, and the
      proinflammatory gene Nos2 (inducible nitric oxide synthase, iNOS). CONCLUSIONS:
      These findings demonstrate that joint pain behaviour is dependent in part on
      descending facilitation via the RVM, and identify a novel pathway driving CXC
      chemokine and iNOS expression in the dorsal horn.

PMID- 24947160
TI  - Volatile organic metabolites identify patients with breast cancer,
      cyclomastopathy, and mammary gland fibroma.
AB  - The association between cancer and volatile organic metabolites in exhaled
      breaths has attracted increasing attention from researchers. The present study
      reports on a systematic study of gas profiles of metabolites in human exhaled
      breath by pattern recognition methods. Exhaled breath was collected from 85
      patients with histologically confirmed breast disease (including 39 individuals
      with infiltrating ductal carcinoma, 25 individuals with cyclomastopathy and from
      21 individuals with mammary gland fibroma) and 45 healthy volunteers. Principal
      component analysis and partial least squares discriminant analysis were used to
      process the final data. The volatile organic metabolites exhibited significant
      differences between breast cancer and normal controls, breast cancer and
      cyclomastopathy, and breast cancer and mammary gland fibroma; 21, 6, and 8
      characteristic metabolites played decisive roles in sample classification,
      respectively (P < 0.05). Three volatile organic metabolites in the exhaled air,
      2,5,6-trimethyloctane, 1,4-dimethoxy-2,3-butanediol, and cyclohexanone,
      distinguished breast cancer patients from healthy individuals, mammary gland
      fibroma patients, and patients with cyclomastopathy (P < 0.05). The identified
      three volatile organic metabolites associated with breast cancer may serve as
      novel diagnostic biomarkers. 

PMID- 24947161
TI  - Fast construction of voxel-level functional connectivity graphs.
AB  - BACKGROUND: Graph-based analysis of fMRI data has recently emerged as a promising
      approach to study brain networks. Based on the assessment of synchronous fMRI
      activity at separate brain sites, functional connectivity graphs are constructed
      and analyzed using graph-theoretical concepts. Most previous studies investigated
      region-level graphs, which are computationally inexpensive, but bring along the
      problem of choosing sensible regions and involve blurring of more detailed
      information. In contrast, voxel-level graphs provide the finest granularity
      attainable from the data, enabling analyses at superior spatial resolution. They
      are, however, associated with considerable computational demands, which can
      render high-resolution analyses infeasible. In response, many existing studies
      investigating functional connectivity at the voxel-level reduced the
      computational burden by sacrificing spatial resolution. METHODS: Here, a novel,
      time-efficient method for graph construction is presented that retains the
      original spatial resolution. Performance gains are instead achieved through data
      reduction in the temporal domain based on dichotomization of voxel time series
      combined with tetrachoric correlation estimation and efficient implementation.
      RESULTS: By comparison with graph construction based on Pearson's r, the
      technique used by the majority of previous studies, we find that the novel
      approach produces highly similar results an order of magnitude faster.
      CONCLUSIONS: Its demonstrated performance makes the proposed approach a sensible
      and efficient alternative to customary practice. An open source software package
      containing the created programs is freely available for download.

PMID- 24947162
TI  - New, goal-directed approach to renal replacement therapy improves acute kidney
      injury treatment after cardiac surgery.
AB  - AIM: The aim of this study was to compare the efficacies of goal-directed renal
      replacement therapy (GDRRT) and daily hemofiltration (DHF) for treating acute
      kidney injury (AKI) patients after cardiac surgery. METHODS: In our retrospective
      study, we included 140 cardiac surgery AKI patients who were treated with renal
      replacement therapy (RRT) from 2002 to 2010. Two patient groups, which comprised
      70 patients who received DHF from January 2002 to September 2008 and 70 patients
      treated with GDRRT from October 2009 to September 2010 were pair-wise compared
      regarding clinical outcomes, as well as the incidence of adverse events. RESULTS:
      In-hospital and 30-day mortality rates were 45.7% and 41.4% in the GDRRT and
      48.6% and 54.3% in the DHF group, respectively, but without statistically
      significant differences. GDRRT patients needed statistically significantly
      shorter hospital and intensive care unit (ICU) stays, less frequent RRT, and
      shorter RRT sessions, whereas, of 11 analyzed renal outcome parameters, 6 values,
      including percentage of complete renal recovery and time for complete renal
      recovery, were significantly superior in the GDRRT group at the time of
      discharge. There was no significant difference in the incidence of adverse events
      within the initial 72 treatment hours between the 2 groups. Hospitalization
      expenses were less in GDRRT group than in DHF group. CONCLUSION: The GDRRT
      approach is superior to DHF for improving renal outcome, as well as reducing the
      time and cost of RRT therapy, for cardiac surgery AKI patients.

PMID- 24947163
TI  - Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the
      production of IL-1beta, IL-6 and IL-10 on human macrophages.
AB  - OBJECTIVE: Tea tree oil (TTO) is an essential oil with anti-inflammatory
      properties, steam distilled from the plant Melaleuca alternifolia. We
      investigated the immunomodulatory properties of TTO and its components (terpinen
      4-ol and alpha-terpineol) using lipopolysaccharide (LPS)-stimulated macrophages.
      METHODS: The ability of TTO, terpinen-4-ol and alpha-terpineol to modulate the
      macrophage response to bacterial LPS stimulation was assessed by ELISA for tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 cytokine
      production and by western blotting for the activation of nuclear factor kappa B
      (NF-kappaB) and p38 mitogen-activated protein kinase (MAPK) signaling, which are
      associated with the expression of pro-inflammatory cytokines. We used a human
      monocytic cell line (U937) differentiated into macrophages. RESULTS: LPS induced
      the production of all cytokines, and TTO and its components significantly reduced
      the production of IL-1beta, IL-6 and IL-10. The production of TNF-alpha was not
      affected by either TTO or its major components. The modulation of cytokine
      production was not mediated by changes in NF-kappaB or p38 MAPK activation.
      CONCLUSION: TTO, terpinen-4-ol and alpha-terpineol can suppress the production of
      inflammatory mediators in LPS-stimulated human macrophages; this inhibition was
      mediated by interfering with the NF-kB, p38 or ERK MAPK pathways.

PMID- 24947164
TI  - Nicotine and oxidative stress induced exomic variations are concordant and
      overrepresented in cancer-associated genes.
AB  - Although the connection between cancer and cigarette smoke is well established,
      nicotine is not characterized as a carcinogen. Here, we used exome sequencing to
      identify nicotine and oxidative stress-induced somatic mutations in normal human
      epithelial cells and its correlation with cancer. We identified over 6,400 SNVs,
      indels and microsatellites in each of the stress exposed cells relative to the
      control, of which, 2,159 were consistently observed at all nicotine doses. These
      included 429 nsSNVs including 158 novel and 79 cancer-associated. Over 80% of
      consistently nicotine induced variants overlap with variations detected in
      oxidative stressed cells, indicating that nicotine induced genomic alterations
      could be mediated through oxidative stress. Nicotine induced mutations were
      distributed across 1,585 genes, of which 49% were associated with cancer. MUC
      family genes were among the top mutated genes. Analysis of 591 lung carcinoma
      tumor exomes from The Cancer Genome Atlas (TCGA) revealed that 20% of non-small
      cell lung cancer tumors in smokers have mutations in at least one of the MUC4,
      MUC6 or MUC12 genes in contrast to only 6% in non-smokers. These results indicate
      that nicotine induces genomic variations, promotes instability potentially
      mediated by oxidative stress, implicating nicotine in carcinogenesis, and
      establishes MUC genes as potential targets. 

PMID- 24947165
TI  - Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in
      gastrointestinal stromal tumors.
AB  - BACKGROUND: Osteopontin (OPN) is a secreted phosphoprotein expressed by
      neoplastic cells involved in the malignant potential and aggressive phenotypes of
      human malignancies, including gastrointestinal stromal tumors (GISTs). Our
      previous study showed that OPN can promote tumor cell proliferation in GISTs. In
      this series, we further aim to investigate the effect of OPN on apoptosis in
      GISTs. METHODS: The expression of apoptotic and anti-apoptotic proteins in
      response to OPN was evaluated. In vitro effects of OPN against apoptosis in GIST
      were also assessed. GIST specimens were also used for analyzing protein
      expression of specific apoptosis-related molecules and their clinicopathologic
      significance. RESULTS: Up-regulation of beta-catenin and anti-apoptotic proteins
      Mcl-1 with concomitant suppression of apoptotic proteins in response to OPN was
      noted. A significant anti-apoptotic effect of OPN on imatinib-induced apoptosis
      was identified. Furthermore, Mcl-1 overexpression was significantly associated
      with OPN and beta-catenin expression in tumor tissues, as well as worse survival
      clinically. CONCLUSIONS: Our study identifies anti-apoptotic effects of OPN that,
      through beta-catenin-mediated Mcl-1 up-regulation, significantly antagonized
      imatinib-induced apoptosis in GISTs. These results provide a potential rationale
      for therapeutic strategies targeting both OPN and Mcl-1 of the same anti
      apoptotic signaling pathway, which may account for resistance to imatinib in
      GISTs.

PMID- 24947166
TI  - Overexpression of prostate tumor overexpressed 1 correlates with tumor
      progression and predicts poor prognosis in breast cancer.
AB  - BACKGROUND: Prostate tumor overexpressed 1 (PTOV1) was demonstrated to play an
      important role in cancer progression and was correlated with unfavorable clinical
      outcome. However, the clinical role of PTOV1 in cancer remains largely unknown.
      This study aimed to investigate the expression and clinicopathological
      significance of PTOV1 in breast cancer. METHODS: The mRNA and protein expression
      levels of PTOV1 were analyzed in 12 breast cancer cell lines and eight paired
      breast cancer tumors by semi-quantitative real time-PCR and western blotting,
      respectively. Immunohistochemistry was performed to assess PTOV1 protein
      expression in 169 paraffin-embedded, archived breast cancer samples. Survival
      analysis and Cox regression analysis were performed to investigate the
      clinicopathological significance of PTOV1 expression. RESULTS: Our data revealed
      that PTOV1 was frequently overexpressed in breast cancer cell lines compared to
      normal human breast epithelial cells and in primary breast cancer samples
      compared to adjacent noncancerous breast tissues, at both the mRNA and protein
      levels. Moreover, high expression of PTOV1 in breast cancer is strongly
      associated with clinicopathological characteristics and estrogen receptor
      expression status (P = 0.003). Breast cancer patients with higher PTOV1
      expression had substantially shorter survival times than patients with lower
      PTOV1 expression (P < 0.001). Univariate and multivariate analysis revealed that
      PTOV1 might be an independent prognostic factor for breast cancer patients (P =
      0.005). CONCLUSIONS: Our study showed that PTOV1 is upregulated in breast cancer
      cell lines and clinical samples, and its expression was positively associated
      with progression and aggressiveness of breast cancer, suggesting that PTOV1 could
      serve as an independent prognostic marker.

PMID- 24947167
TI  - Current challenges in the microbiological diagnosis of invasive aspergillosis.
AB  - The diagnosis of invasive aspergillosis is challenging because no sufficiently
      sensitive or specific tests have been developed to date. Infection can only be
      confirmed using histology, although this approach is unavailable in many
      patients. Therefore, diagnosis of invasive aspergillosis is based on a
      combination of the presence of host factors, radiological and clinical findings,
      and mycological criteria. In clinical practice, lack of optimal diagnostics often
      leads to empirical therapy and great cost and toxicity. Mycological criteria
      include the isolation of Aspergillus from clinical samples or the detection of
      biomarkers in fluids. Culture is cheap and easy and enables the identification of
      fungi and performance of antifungal susceptibility testing; however, it has low
      sensitivity and specificity. Non-culture-based diagnosis is based on the
      detection of fungal biomarkers such as galactomannan or (1 -> 3)-beta-D-glucan in
      normally sterile body fluids. These procedures enable faster and more sensitive
      and specific detection of Aspergillus; however, diagnostic accuracy is affected
      by the patient's underlying condition. Finally, while detection of Aspergillus
      DNA is promising, the lack of standardization limits its inclusion as a
      mycological criterion for the definition of probable invasive aspergillosis. New
      diagnostic procedures based on lateral flow technology are also promising but
      need further evaluation. In the present review, we discuss current culture-based
      and non-culture-based procedures for the microbiological diagnosis of invasive
      aspergillosis.

PMID- 24947168
TI  - Zinc acquisition: a key aspect in Aspergillus fumigatus virulence.
AB  - Zinc is an essential micronutrient required for the growth of all microorganisms.
      To grow in the lungs of a susceptible patient Aspergillus fumigatus must obtain
      zinc from the surrounding tissues. The concentration of Zn(2+) ions in living
      tissues is much lower than that required for optimal fungal growth in vitro
      because most of them are tightly bound to proteins at the physiological pH.
      However, A. fumigatus has several zinc transporters (ZrfA, ZrfB and ZrfC) that
      enable it to uptake zinc efficiently under the extreme zinc-limiting conditions
      provided by a susceptible host. The ZafA transcriptional regulator induces the
      expression of these transporters and is essential for virulence. ZrfC is required
      for fungal growth within the host tissues, whereas ZrfA and ZrfB play an
      accessory role. The zinc-scavenging capacity of ZrfC relies on its unusually long
      N-terminus. In addition, ZrfC also enables A. fumigatus to overcome the
      inhibitory effect of calprotectin, which is an antimicrobial Zn/Mn-chelating
      protein synthesized in high amounts by neutrophils, even in immunosuppressed non
      leucopenic animals. In summary, the regulation of zinc homeostasis and zinc
      acquisition could be promising targets for the discovery and development of a new
      generation of antifungals for the treatment of invasive pulmonary aspergillosis. 

PMID- 24947169
TI  - Aspergillus cell wall and biofilm.
AB  - The fungal cell is surrounded by a cell wall that acts as a sieve and a reservoir
      for effector molecules that play an active role during infection. This cell wall
      is essential for fungal growth as well as for resisting host defense mechanisms.
      The Aspergillus fumigatus cell wall is almost exclusively composed of
      polysaccharides. The fibrillar core is composed of a branched beta-(1,3)-glucan
      to which chitin, beta-(1,3)-/beta-(1,4)-glucan, and galactomannan are covalently
      bound. The alkali-soluble amorphous fraction is mainly composed of alpha-(1,3)
      glucan that has adhesive property and stabilizes the cell wall. Although the same
      polysaccharides are found in the cell wall of different A. fumigatus morphotypes
      (conidia and hyphae), their concentration and localization are different.
      Conidial (the morphotype that mainly enters host respiratory system) cell wall is
      covered by an outer layer of rodlets and melanin, which confers hydrophobic
      properties and imparts immunological inertness. In contrast, outer layer of the
      hypha contains galactosaminogalactan, recently identified as an A. fumigatus
      virulence factor. The hypha grows either as a network of agglutinated and
      hydrophobic mass (called mycelium) embedded in an extracellular matrix (ECM) rich
      in polysaccharides, hydrophobin, and melanin or segregated without ECM. 

PMID- 24947170
TI  - Burden and distinctive character of allergic bronchopulmonary aspergillosis in
      India.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is an insidious pulmonary disorder
      caused by hypersensitivity reactions mounted against Aspergillus fumigatus.
      Usually, complicating the course of patients with asthma and cystic fibrosis, the
      affliction has recently been described in chronic obstructive pulmonary disease
      and pulmonary tuberculosis-related fibrocavitary disease. Patients commonly
      present with poorly controlled asthma, recurrent pulmonary infiltrates and
      bronchiectasis. More than six decades have elapsed since the first description of
      this entity; however, the condition remains poorly understood. The International
      Society for Human and Animal Mycology has formed a working group to address the
      deficiencies associated with understanding of this disorder. New criteria have
      been laid down for diagnosis and staging of the disorder, so as to simplify the
      identification and management of this condition. This review summarizes the
      recent advances that have taken place in this condition with special emphasis on
      the burden and distinct character of ABPA in the Indian subcontinent. 

PMID- 24947171
TI  - Phaeohyphomycoses in a free-ranging loggerhead turtle (Caretta caretta) from
      Southern Brazil.
AB  - This report describes the occurrence of mycotic infection in a loggerhead turtle,
      Caretta caretta, found on Mostardas beach in the state of Rio Grande do Sul,
      Southern Brazil. The specimen was observed alive, emaciated, and died the
      following day. A necropsy was performed soon after death and tissue samples
      routinely processed for histopathological and molecular evaluation. Significant
      pathological alterations included multifocal to coalescing, 0.5-4 cm in diameter
      nodules were observed throughout the peritoneum and kidneys that revealed
      caseous, grayish content when sectioned; histopathological evaluation revealed
      severe peritonitis and nephritis associated with intralesional fungi. Fungal PCR
      that targeted the internal transcribed spacer region of fungi revealed three
      different species of fungi: Cladosporium cladosporioides and Alternata
      arborescens within the kidneys while Ampelomyces sp. was identified within
      peritoneal granulomas. C. cladosporioides and A. arborescens are melanized fungi
      that produce phaeohyphomycosis in a wide range of species. However, the
      importance of the identification of the mycoparasite Ampelomyces sp. DNA within
      the peritoneal granulomas remains unclear.

PMID- 24947172
TI  - Mucor irregularis infection around the inner canthus cured by amphotericin B: a
      case report and review of published literatures.
AB  - We report a case of primary cutaneous mucormycosis caused by Mucor irregularis. A
      47-year-old farmer was presented to our clinic with the history of progressive
      red plaque around the inner canthus following dacryocystectomy about a year
      earlier. Linear, aseptate hyphae were seen by direct KOH examination and in
      biopsy. Fungal culture revealed light yellow filamentous colonies that were
      identified as Mucor irregularis by nucleotide sequencing of rRNA gene.
      Amphotericin B and dexamethasone were used in gradually increasing dosage. The
      treatment lasted 43 days, and the patient received 760 mg total amphotericin B.
      The patient was discharged after 2 months of treatment. The plaque became smooth,
      and fungal culture was negative. There was no recurrence for half a year through
      telephone follow-ups. A review of published studies revealed 23 cases of Mucor
      irregularis infection. Most cases resulted following injuries or surgical
      complications. Farmers and manual laborers were most at risk with males
      outnumbering females among patients. Amphotericin B and its liposomal
      preparations remain most effective treatment choices.

PMID- 24947173
TI  - Cerebral proton magnetic resonance spectroscopy demonstrates reversibility of N
      acetylaspartate/creatine in gray matter after delayed encephalopathy due to
      carbon monoxide intoxication: a case report.
AB  - INTRODUCTION: Predictive markers for long-term outcome in carbon monoxide
      intoxicated patients with late encephalopathy are desired. Here we present the
      first data demonstrating a full reversibility pattern of specific brain
      substances measured by cerebral proton magnetic resonance spectroscopy in a
      carbon monoxide-intoxicated victim. This may provide clinicians with important
      information when estimating patient outcome. CASE PRESENTATION: We report the
      case of a 40-year-old Caucasian woman with severe carbon monoxide poisoning who
      was treated with five repetitive sessions of hyperbaric oxygen therapy in a
      multiplace chamber (100 percent oxygen with a ventilator, 90 minutes exposure to
      2.8 atmospheres absolute). Initially, our patient recovered completely after
      three days of hospitalization, but became encephalopathic after a lucid interval
      of four weeks. An examination of the brain with cerebral proton magnetic
      resonance spectroscopy showed a dramatically decrease in N-acetylaspartate to
      total creatine ratios and elevated lactate levels in the gray matter.
      Subsequently, our patient received six additional sessions of hyperbaric oxygen
      therapy with only minimal recovery. At six-month follow-up our patient showed
      significant improvement in cognition and neuromuscular coordination.
      Extraordinarily, the cerebral proton magnetic resonance spectroscopy measurements
      at relapse compared to measurements at follow-up (217 days post insult) revealed
      full reversal of the severe abnormalities in mid-occipital gray matter and
      partial reversal in white matter. CONCLUSIONS: The present case indicates that
      cerebral proton magnetic spectroscopy provides valuable information on brain
      metabolism in patients presenting with delayed encephalopathy after acute carbon
      monoxide intoxication. The full reversal of N-acetylaspartate to total creatine
      ratios in gray matter has, to our knowledge, never been described before and
      shows that severe, initial measurements may not predict poor long-term patient
      outcome.

PMID- 24947174
TI  - Functional analysis of FABP3 in the milk fat synthesis signaling pathway of dairy
      cow mammary epithelial cells.
AB  - Milk fat is the major energy component of milk, and regulation of its production
      relies on transcription factors sterol regulatory element-binding protein 1
      (SREBP1) and peroxisome proliferator-activated receptor gamma (PPARgamma). As one
      of the target genes of SREBP1 and PPARgamma, fatty acid-binding protein 3(FABP3)
      is the main protein allowing for rapid diffusion and selective targeting of long
      chain fatty acids toward specific organelles for metabolism. Whether FABP3 plays
      an important role in milk fat synthesis signaling pathway is largely unknown. In
      this study, we observed the effects of FABP3 overexpression and gene silencing in
      dairy cow mammary epithelial cells, as well as the effects of oleic acid, stearic
      acid, and palmitic acid on the expressions of FABP3 and lipid droplet formation,
      by using quantitative reverse transcriptase (qRT)-PCR, Western blotting, and
      fluorescent immunostaining techniques. FABP3 upregulated the expression of SREBP1
      and PPARgamma to increase lipid droplet accumulation. Oleic acid, stearic acid,
      and palmitic acid also increased lipid droplet accumulation by affecting
      expression of FABP3. These findings shed new insights for understanding the
      mechanism of FABP3 in regulating milk fat synthesis. 

PMID- 24947176
TI  - Parathyroid dual tracer subtraction scintigraphy: small regions method for
      quantitative assessment of parathyroid adenoma uptake.
AB  - OBJECTIVE: The aim was quantitative assessment of parathyroid adenoma (PTA)
      uptake in dual tracer dynamic scintigraphy. METHODS: In 78 patients, median age
      58 (19-80) years, surgically treated for primary hyperparathyroidism (PHPT), with
      parathyroid hormone median 125 (70-658) pg/ml, we performed preoperative
      parathyroid scintigraphy, following EANM guidelines of subtraction and double
      phase protocol (2009) using two tracers: Tc-99m pertechnetate and Tc-99m MIBI. In
      addition to standard subtraction processing and visual interpretation of delayed
      MIBI planar images of neck and mediastinum in oblique sections (positions
      according to ultrasound PTA localisation), we developed Submarine processing
      software that enables selecting custom regions grid sizes >=6 mm (as this
      solution was not present in commercial software) to follow time activity curve
      changes in thyroid tissue and PTA. Histopathology in 53/78 patients revealed PHPT
      and in 25/78 patients thyroid nodular disease only, and thyroid malignancy
      occurred in total of 15/78 (19 %) patients. PHPT group included 44 solitary PTA,
      8 patients with hyperplasia and one parathyroid carcinoma. The median macroscopic
      volume of PTA was 717.5 (15-6125) mm(3). Concomitant PHPT and thyroid nodular
      disease occurred in 24/53 patients and among them 8 patients had thyroid
      malignancies. RESULTS: PTA showed typical pattern of late peak on time activity
      curves characterized by median start time on 15 (10-25) min, the peak amplitude
      mean 19 (+/-5) % above thyroid declining washout curve, and duration of peak 6 (4
      10) min, allowing PTA to "emerge" like submarine, independent from thyroid tissue
      and lesions. The ratio of PTA-to-normal thyroid uptake at peak maximum was 1.35
      (+/-0.21). The thyroid TACs results of normal 29/78 (37 %) patients, benign
      nodular 34/78 (44 %) patients, and malignancy in 15 (19 %) patients were all
      presented by declining exponential curves. The slope analysis of TACs in normal
      thyroid tissue, thyroid benign and malignant lesions (linear fitted logarithm of
      TAC) showed no difference (the same negative slope: -0.04). Submarine processing
      was sensitive in detection of small lesions, in hyperplasia, and concomitant
      thyroid nodular disease. CONCLUSIONS: The novel Submarine processing confirmed
      specific PHPT pattern and was effective in the group with potential pitfalls of
      standard interpretation, increasing sensitivity and specificity of standard
      processing subtraction algorithm. Prolonged MIBI accumulation was present in
      malignant as well as benign thyroid nodules with identical TAC slope.

PMID- 24947175
TI  - Moving towards the immunodiagnosis of staphylococcal intramammary infections.
AB  - Bovine mastitis is the primary disease of dairy cattle that has a great impact on
      the dairy industry. It is estimated that worldwide economic losses due to
      mastitis range between US$82 and US$131 per cow/year. A fast and efficient
      diagnosis of the disease remains a major bottleneck that directly influences the
      speed with which treatment decisions and management are undertaken.
      Microbiological culture remains the gold standard in the identification of
      bacteria that cause mastitis, but the method has inherent limitations, such as a
      delay in obtaining results and cost, and requires special care during the
      collection and processing of the sample. For this reason, multiple groups have
      devoted efforts to develop alternative methods that, preferably, can be easily
      accomplished in the field. The specificity of the antigen-antibody reaction has
      enabled the emergence of major diagnostic methods used in clinical practice, such
      as immunoassays, which have significant advantages in terms of speed,
      sensitivity, specificity, and portability. Commercially, immunodiagnostics have
      been used in the detection of various diseases in cattle. However, in several
      cases, only a presumptive diagnosis can be made, which requires confirmation
      using culture-based methods. This review discusses the immunological-based assays
      developed since the 1990s for the detection of Staphylococcus aureus, which is
      considered the primary pathogen of contagious bovine mastitis. Although no ideal
      antigens ensure the accurate performance of tests and the costs need to be
      reduced to allow for good market competitiveness, immunoassays, particularly
      lateral flow immunoassay and immunoagglutination, have emerged as promising tests
      to be used in the field. 

PMID- 24947177
TI  - Effects of sex hormones on inflammatory response in male and female vascular
      endothelial cells.
AB  - PURPOSE: Gender-related differences in sex hormones might have a key role in the
      development of atherosclerosis though direct vascular effects of sex hormones are
      not yet well understood. Thus, the main purpose of this study was to compare the
      effects of sex hormones on inflammatory response in Human Umbilical Vein
      Endothelial Cells (HUVECs) obtained from both male and female donors. METHODS: We
      analyzed the expression of receptors and enzymes relevant to the action of
      androgens (AR, 5alpha-reductase 1 and 5alpha-reductase 2) and estrogens (ERalpha,
      ERbeta, and aromatase) in male and female HUVECs. Furthermore, we analyzed the
      effect of testosterone (T), 17beta-estradiol (E2), dihydrotestosterone (DHT), and
      several androgenic-anabolic steroids (AAS) on VCAM-1, ICAM-1, and E-selectin gene
      expression and on adhesion of U937 cells to TNF-alpha-stimulated male and female
      HUVECs. RESULTS: Our results reveal that in HUVECs, regardless of gender, the
      components involved in the androgen action pathway are predominant as compared to
      those of estrogen action pathway. In both HUVEC genders, the inflammatory effect
      of TNF-alpha was amplified by co-administration of T or DHT and several AAS
      frequently used in doping, while E2 had no effect. CONCLUSIONS: This is the first
      study analyzing, under identical culture conditions, the key components of sex
      hormone response in male and female HUVECs and the possible role of sex hormones
      in regulating the endothelial inflammatory response. The data obtained in our
      experimental system showed a pro-inflammatory effect of androgens, while
      conclusively excluding any protective effect for all the tested hormones.

PMID- 24947178
TI  - Anti thyroperoxidase and anti thyroglobulin antibodies in diabetic pregnancies.
AB  - INTRODUCTION: Thyroid autoimmunity is very frequent in women of reproductive age
      and is associated with many adverse pregnancy outcomes; also, diabetes mellitus
      in pregnancy, of any type, is associated to many complications. In type 1
      diabetes, the prevalence of thyroid autoimmunity is higher than in healthy
      population. Instead, the association of thyroid autoimmunity with other types of
      diabetes is less clear; however, there are some studies claiming that the
      prevalence is higher in gestational diabetes too. Poor data about type 2 diabetes
      in pregnancy are available. It is also unclear how diabetes and thyroid function
      influence each other and if levothyroxine therapy is necessary in pregnancy with
      positive autoimmunity but normal thyroid function. MATERIALS AND METHODS: The aim
      of this article was to find in the literature studies on thyroid autoimmunity in
      different types of diabetes in pregnancy, in order to detect any difference in
      prevalence. Data were found through pubmed database from 1990 to 2013.
      CONCLUSIONS: Several studies found a higher prevalence of thyroid autoimmunity in
      GDM compared to healthy controls; therefore it would be appropriate to extend
      screening for thyroid diseases to women with GDM. More studies are needed on the
      possible requirement of therapy for thyroid autoimmunity when the function is
      normal.

PMID- 24947179
TI  - Loss of histone demethylase KDM6B enhances aggressiveness of pancreatic cancer
      through downregulation of C/EBPalpha.
AB  - Genetic mutations in pancreatic ductal adenocarcinoma (PDAC) with critical roles
      have been well examined. The recent discovery of alterations in genes encoding
      histone modifiers suggests their possible roles in the complexity of cancer
      development. We previously reported loss of heterozygosity of the KDM6B gene,
      which encodes a histone demethylase for trimethylated histone H3 lysine 27, a
      repressive chromatin mark, in PDAC cells. In this study, we demonstrated that
      loss of KDM6B enhanced aggressiveness of PDAC cells. KDM6B has been regarded as a
      tumor suppressor that mediates oncogenic KRAS-induced senescence. Consistently,
      KDM6B was highly expressed in pancreatic precancerous lesions (pancreatic
      intraepithelial neoplasms); then, the expression decreased as the malignant grade
      progressed. We found that knockdown of KDM6B in PDAC cells promoted tumor sphere
      formation and increased peritoneal dissemination and liver metastasis in vivo.
      Microarray and chromatin immunoprecipitation analysis implicated CEBPA for
      aggressiveness induced by KDM6B knockdown. CEBPA knockdown recapitulated the
      phenotypic change of PDAC cells after KDM6B knockdown, which was reversed by
      forced expression of C/EBPalpha. Moreover, similar protein expression patterns of
      KDM6B and C/EBPalpha in human PDAC emphasized their functional correlation.
      Notably, pharmacological inhibition of the H3K27 methylase EZH2 in PDAC cells
      inhibited tumor sphere formation along with the upregulation of CEBPA expression,
      and this effect was impaired in KDM6B knockdown cells, highlighting the role for
      KDM6B in the activation of CEBPA. Together, our results propose a significant
      role for the KDM6B-C/EBPalpha axis in the PDAC phenotype. 

PMID- 24947180
TI  - Immunomodulatory drugs improve the immune environment for dendritic cell-based
      immunotherapy in multiple myeloma patients after autologous stem cell
      transplantation.
AB  - Multiple myeloma (MM) is characterized by a malignant proliferation of plasma
      cells in the bone marrow with associated organ damage. Although the prognosis of
      MM has improved recently, the disease remains incurable for the large majority of
      patients. The eradication of residual disease in the bone marrow is a main target
      on the road toward cure. Immune cells play a role in the control of cancer and
      can be tools to attack residual MM cells. However, the myeloma-associated immune
      deficiency is a major hurdle to immunotherapy. We evaluated ex vivo the effects
      of low doses of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide
      on several immune cell types from MM patients after autologous stem cell
      transplantation and with low tumor burden. We observed that these drugs increased
      CD4(+) and CD8(+) T-cell proliferation and cytokine production, enhanced the
      lytic capacity of cytotoxic T lymphocytes and reduced the suppressive effects of
      regulatory T cells on CD8(+) T-cell responses. In addition, we found that
      functional dendritic cells (DCs) can be generated from mononuclear cells from MM
      patients. The presence of IMiDs improved the quality of antigen-specific T cells
      induced or expanded by these DCs as evidenced by a higher degree of T-cell
      polyfunctionality. Our results provide a rationale for the design of early phase
      clinical studies to assess the efficacy of DC-based immunotherapy in combination
      with posttransplant maintenance treatment with IMiDs in MM. 

PMID- 24947181
TI  - Significance of cartilage endplate within herniated disc tissue.
AB  - PURPOSE: Disc herniations sometimes contain hyaline cartilage fragments, but
      their origins and significance are uncertain. METHODS: Herniations were removed
      surgically from 21 patients (aged 35-74 years) whose main symptom was sciatica
      (10 patients) or back pain (11 patients). Frozen sections, 5 um thick, were
      examined histologically, and antibodies were used to label the matrix-degrading
      enzyme MMP 1, pro-inflammatory mediator TNFalpha, and cell proliferation marker
      Ki-67. Proportions of each tissue type were quantified by image analysis.
      Cartilage and bone components of the endplate were examined in 7-um frozen
      sections from 16 cadaveric spines, aged 61-98 years. RESULTS: Cartilage fragments
      were found in 10/21 herniations. They averaged 5.0 mm in length, comprised 25 %
      of the herniation area, and two had some bone attached. Hyaline cartilage was
      more common in herniations from patients with sciatica (7/10) than with back pain
      (3/11, P = 0.050), and the area (%) of the herniation occupied by the cartilage
      was greater in sciatica patients (P < 0.05). Cartilage fragments showed little
      evidence of swelling, proteoglycan loss or inflammatory cell invasion, although
      cell clustering was common, and TNFalpha was sometimes expressed. Each cartilage
      fragment showed at least one straight edge, as if it had been peeled off the bony
      endplate, and this mechanism of failure was demonstrated in preliminary
      mechanical experiments. CONCLUSION: Disc herniations often include hyaline
      cartilage pulled from the vertebral endplates. Cartilage fragments show little
      swelling or proteoglycan loss, and may be slow to resorb, increasing the risk of
      persisting sciatica. Loss of cartilage will increase endplate permeability,
      facilitating endplate inflammation and disc infection.

PMID- 24947182
TI  - Five-year results of lumbar disc prostheses in the SWISSspine registry.
AB  - PURPOSE: The Swiss Federal Office of Public Health demanded a nationwide HTA
      registry for lumbar total disc arthroplasty (TDA), to decide about its
      reimbursement. The goal of the SWISS spine registry is to generate evidence about
      the safety and efficiency of lumbar TDA. METHODS: Two hundred forty-eight cases
      treated between 3-2005 and 6-2006, who were eligible for the 5-year follow-up
      were included in the study. Follow-up rates for 3-6 months, 1, 2 and 5 years were
      85.9, 77.0, 44.0 and 51.2 %, respectively. Outcome measures were back and leg
      pain, medication consumption, quality of life, intraoperative and postoperative
      complication and revision rates. Additionally, segmental mobility, ossification,
      adjacent and distant segment degeneration were analysed at the 5-year follow-up.
      RESULTS: There was a significant, clinically relevant and lasting reduction of
      back (preop/postop 73/29 VAS points) and leg pain (preop/postop VAS 55/22) and a
      consequently decreased analgesics consumption and quality of life improvement
      (preop/postop 0.30/0.76 EQ-5D score points) until 5 years after surgery. The
      rates for intraoperative and early postoperative complications were 4.4 and 3.2
      %, respectively. The overall complication rate during five postoperative years
      was 23.4 %, and the adjacent segment degeneration rate was 10.7 %. In 4.4 % of
      patients, a revision surgery was performed. Cumulative survivorship probability
      for a revision/re-intervention-free 5-year postoperative course was 90.4 %. At
      the 5-year follow-up, the average range of motion of the mobile segments (86.8 %)
      was 9.7 degrees . In 43.9 % of patients, osteophytes at least potentially
      affecting the range of motion were seen. CONCLUSIONS: Lumbar TDA appeared as
      efficient in long-term pain alleviation, consequent reduction of pain medication
      consumption and improvement of quality of life. The procedure also appeared
      sufficiently safe, but surgeons have to be aware of a list of potential adverse
      events. The outcome is stable over the 5-year postoperative period. The vast
      majority of treated segments remained mobile after 5 years, although almost half
      of patients showed osteophytes.

PMID- 24947183
TI  - Does delaying surgery in immature adolescent idiopathic scoliosis patients with
      progressive curve, lead to addition of fusion levels?
AB  - PURPOSE: To analyze the changes in the curve extent, pattern and the fusion level
      in adolescent idiopathic scoliosis (AIS) patients who undergo delayed surgery
      instead of early surgery. METHODS: Thirty-five immature AIS patients whose
      radiographs demonstrated an initial primary curve of more than 40 degrees  with a
      subsequent increase of 10 degrees  before attaining skeletal maturity with brace
      were enrolled. The initial and the final radiographs taken before surgery were
      compared to assess the changes in curve extent, pattern and the fusion levels as
      recommended by King's, Lenke's and Suk's guidelines. RESULTS: The average age of
      35 AIS patients was 12.7 +/- 1.6 years. The time interval between initial and
      final radiography was 39.3 +/- 20.2 months and the degree of progress of the
      primary curve was 13 +/- 9.7 degrees . Fusion levels changed in 33 (94.2%), 33
      (94.2%) and 32 (91.4%) patients according to King's, Lenke's and Suk's
      guidelines, respectively. Curve pattern was changed in 2 (5.7%), 12 (34.3%) and
      10 (28.6) patients by King's, Lenke's and Suk's guidelines. The mean number of
      levels requiring fusion increased from 9.4 +/- 2.1 at initial visit to 11.1 +/-
      1.8 at the final follow-up using King's guidelines, 9.7 +/- 2.2-11.6 +/- 2.0 as
      per Lenke's guidelines and 9.1 +/- 2.0-11.5 +/- 2.3 when fusion was planned using
      Suk's guidelines (p < 0.001 in all guidelines). CONCLUSIONS: Delay of surgery in
      immature AIS patients whose Cobb's angle exceed 40 degrees  initially and showing
      subsequent progression of the curve, of more than 10 degrees  can lead to
      alterations in the curve pattern and the need for increase in fusion levels.

PMID- 24947184
TI  - Acute gastric dilation and necrosis as a late complication following laparoscopic
      Nissen fundoplication.

PMID- 24947185
TI  - High-definition white-light (HDWL) colonoscopy and higher adenoma detection rate
      and the potential for paradoxical over surveillance.
AB  - BACKGROUND: Patients undergoing high-definition white-light colonoscopy by a high
      adenoma detector may have a lower risk of interval adenoma detection on follow-up
      colonoscopy and may require less frequent follow-up but may paradoxically be
      assigned to more frequent surveillance when more adenomas are detected. AIMS: To
      evaluate whether high-definition white-light colonoscopy (vs. standard-definition
      white-light colonoscopy) and endoscopist adenoma detection rate (ADR) at index
      colonoscopy are associated with increased likelihood of adenomas at follow-up.
      METHODS: Longitudinal follow-up of prior cross-section cohort study of patients
      who underwent colonoscopy at baseline with at least one detected adenoma was
      included. Associations of type of white-light at index colonoscopy and the ADR of
      the endoscopist at index colonoscopy (high vs. low adenoma detector) were
      evaluated with various adenoma and polyp detection endpoints. Eighteen
      endoscopists were classified as high and low adenoma detectors based on the
      median ADR of 0.255. RESULTS: There were no significant differences in subsequent
      interval adenoma or polyp detection endpoints with regard to whether baseline
      exam was performed with high-definition white-light or standard-definition white
      light colonoscopy nor between high and low ADR after adjusting for multiple
      testing (P <= 0.0029 considered significant). Prior to multiple testing
      adjustment, there was a significantly lower detection rate of hyperplastic polyps
      in the left colon (24 vs. 35 %, OR: 0.56, P = 0.033) at follow-up colonoscopy
      when baseline exam was performed with high-definition white-light index
      colonoscopy. CONCLUSIONS: The results of this study do not support adjusting
      colonoscopy surveillance guidelines based on type of colonoscopy performed or the
      endoscopist's ADR.

PMID- 24947186
TI  - Snail1 expression is required for sarcomagenesis.
AB  - Snail1 transcriptional repressor is a major inducer of epithelial-to mesenchymal
      transition but is very limitedly expressed in adult animals. We have previously
      demonstrated that Snail1 is required for the maintenance of mesenchymal stem
      cells (MSCs), preventing their premature differentiation. Now, we show that
      Snail1 controls the tumorigenic properties of mesenchymal cells. Increased Snail1
      expression provides tumorigenic capabilities to fibroblastic cells; on the
      contrary, Snail1 depletion decreases tumor growth. Genetic depletion of Snail1 in
      MSCs that are deficient in p53 tumor suppressor downregulates MSC markers and
      prevents the capability of these cells to originate sarcomas in immunodeficient
      SCID mice. Notably, an analysis of human sarcomas shows that, contrarily to
      epithelial tumors, these neoplasms display high Snail1 expression. This is
      particularly clear for undifferentiated tumors, which are associated with poor
      outcome. Together, our results indicate a role for Snail1 in the generation of
      sarcomas. 

PMID- 24947188
TI  - Regulatory B cells correlate with HIV disease progression.
AB  - A rare subset of IL-10-producing B cells, named Breg, was recently identified in
      mice and humans. Currently, there are no unified cell surface markers to identify
      Breg, and the relationship between the frequency of Breg and HIV disease
      progression in chronic HIV infection is unclear. In the present study, we
      determined whether the cell surface markers of Breg reported for other diseases
      are suitable for identifying Breg in HIV-infected patients. In addition, we
      examined the relationship between Breg and HIV disease progression. We found that
      Breg frequency correlated positively with viral load and negatively with CD4
      count in chronic HIV infection. Following antiretroviral treatment, the CD4 count
      increased and the frequency of Breg decreased stepwise. There was no difference
      in IL-10 expression of CD1d(hi) or CD1d(lo) cells isolated from HIV-infected
      patients. Therefore, CD1d may not be a marker of Breg in HIV-infected patients. 

PMID- 24947187
TI  - CSNK1E/CTNNB1 are synthetic lethal to TP53 in colorectal cancer and are markers
      for prognosis.
AB  - Two genes are called synthetic lethal (SL) if their simultaneous mutations lead
      to cell death, but each individual mutation does not. Targeting SL partners of
      mutated cancer genes can kill cancer cells specifically, but leave normal cells
      intact. We present an integrated approach to uncovering SL pairs in colorectal
      cancer (CRC). Screening verified SL pairs using microarray gene expression data
      of cancerous and normal tissues, we first identified potential functionally
      relevant (simultaneously differentially expressed) gene pairs. From the top
      ranked pairs, ~20 genes were chosen for immunohistochemistry (IHC) staining in
      171 CRC patients. To find novel SL pairs, all 169 combined pairs from the
      individual IHC were synergistically correlated to five clinicopathological
      features, e.g. overall survival. Of the 11 predicted SL pairs, MSH2-POLB and
      CSNK1E-MYC were consistent with literature, and we validated the top two pairs,
      CSNK1E-TP53 and CTNNB1-TP53 using RNAi knockdown and small molecule inhibitors of
      CSNK1E in isogenic HCT-116 and RKO cells. Furthermore, synthetic lethality of
      CSNK1E and TP53 was verified in mouse model. Importantly, multivariate analysis
      revealed that CSNK1E-P53, CTNNB1-P53, MSH2-RB1, and BRCA1-WNT5A were independent
      prognosis markers from stage, with CSNK1E-P53 applicable to early-stage and the
      remaining three throughout all stages. Our findings suggest that CSNK1E is a
      promising target for TP53-mutant CRC patients which constitute ~40% to 50% of
      patients, while to date safety regarding inhibition of TP53 is controversial.
      Thus the integrated approach is useful in finding novel SL pairs for cancer
      therapeutics, and it is readily accessible and applicable to other cancers. 

PMID- 24947189
TI  - Clinical image quality in daily practice of breast cancer mammography screening.
AB  - OBJECTIVE: To assess the quality of screening mammograms performed in daily
      practice in the Quebec Breast Cancer Screening Program. SUBJECTS AND METHODS:
      Clinical image quality of a random subsample of 197 screening mammograms
      performed in 2004-2005 was independently evaluated by 2 radiologists based on the
      criteria by Canadian Association of Radiologists (CAR). When disagreement
      occurred for overall judgement or positioning score, the mammograms were reviewed
      by a third radiologist. Cohen's kappas for interrater agreement were computed.
      Multivariable robust Poisson regression models were used to study associations of
      overall quality and positioning with body mass index (BMI) and breast density.
      RESULTS: The CAR criteria were not satisfied for 49.7% of the mammograms.
      Positioning was the quality attribute most often deficient, with 37.2% of
      mammograms failing positioning. Interrater agreement ranged from slight (kappa =
      0.02 for compression and sharpness) to fair (kappa = 0.30 for exposure). For
      overall quality, women with a BMI >= 30 kg/m(2) had a failure proportion of 67.5%
      compared with 34.9% for women with a BMI<25 kg/m(2) (risk ratio 2.1 [95%
      confidence interval, 1.5-3.0]). For positioning, women with a BMI >= 30 kg/m(2)
      had a failure proportion of 53.8% compared with 27.9% for women with a BMI < 25
      kg/m(2) (risk ratio 1.9 [95% confidence interval, 1.2-3.1]). Effects of breast
      density on image quality differed among radiologists. CONCLUSION: Despite
      measures to ensure high-quality imaging, including CAR accreditation,
      approximately half of this random sample of screening mammograms failed the CAR
      quality standards. It would be important to define quality targets for screening
      mammograms carried out in daily practice to interpret such observations.

PMID- 24947190
TI  - Bacterial (intramembrane-sensing) histidine kinases: signal transfer rather than
      stimulus perception.
AB  - Most membrane-anchored histidine kinases (HKs) of bacterial two-component systems
      (2CSs) contain an extracellular input domain that is thought to be responsible
      for sensing an environmental cue. By contrast, intramembrane-sensing HKs (IM-HKs)
      lack a sensory domain and cannot perceive their stimuli directly. Instead, an N
      terminal signal transfer region, consisting solely of two transmembrane helices,
      presumably connects the IM-HKs with accessory membrane proteins that function as
      the true sensors. This intermolecular signal transfer, in combination with
      intramolecular signal conversion, provides HKs with versatile signaling relays to
      connect, integrate, and amplify external signals from different sensory inputs
      ultimately to modulate the activity of the corresponding kinase domain. 

PMID- 24947191
TI  - Remote ischemic preconditioning as prevention of transfusion-related acute lung
      injury.
AB  - Transfusion-related acute lung injury (TRALI) is a serious complication of
      transfusion medicine, considered now as the leading cause of transfusion-related
      mortality. It may occur in up to 1 in 5000 transfusions and carries an elevated
      morbidity and mortality. Clinically it presents as hypoxia and non-cardiogenic
      pulmonary edema, usually within 6h of transfusion. It consists of an
      immunological phenomenon involving the activation of neutrophils and endothelial
      injury, leading to capillary leak and pulmonary edema, mechanisms shared with
      lung ischemia-reperfusion (IR) injury. Brief and repetitive periods of ischemia
      in an organ or limb have been shown to protect against subsequent major IR injury
      in distant organs, a phenomenon called remote ischemic preconditioning (RIPC).
      Limb RIP has been shown to protect the lung against IR injury trough modulation
      of endothelial function as well as neutrophil activation and infiltration. The
      protective effects of RIPC on the lung have been confirmed in clinical trials of
      orthopedic and cardiothoracic surgery. RIPC is a safe, tolerable and cheap
      procedure. I propose that limb RIPC could be used as a preventive strategy
      against the development of TRALI. 

PMID- 24947192
TI  - Deviation of the fully protracted tongue: is it a reliable indicator for language
      cerebral dominance?
AB  - Since its introduction in 1960, The Wada test has been considered the gold
      standard for language lateralization prior to ablative brain surgery. Due to the
      invasive nature of The Wada test several non-invasive techniques have been
      alternatively adopted. Recently, it has been suggested that the tongue deviates
      toward the language dominant cerebral hemisphere on full protraction. This
      suggestion is based on the important role the tongue plays in articulation and on
      the close anatomical relationship between the cortical tongue motor area and the
      motor speech area. It was proposed that this phenomenon could serve as a reliable
      and simple method for language brain lateralization. However, this hypothesis is
      still open for verification. In an attempt to correlate tongue deviation and
      language cerebral dominance we present and discuss in this paper the results of a
      study conducted on 339 free adult Jordanian volunteers. Tongue deviation and
      handedness were determined and statistically correlated. Our results showed that
      62% of test subjects did not show any tongue deviation on full protrusion.
      Additionally, 9% of test subjects showed left-sided tongue deviation on full
      protraction in spite of 90% right handedness with presumed left language dominant
      cerebral hemisphere. We conclude that, at least in Jordanians, tongue deviation
      cannot be considered as a reliable indicator for language lateralization. 

PMID- 24947193
TI  - Fluoroquinolone antibiotics and type 2 diabetes mellitus.
AB  - Exposure to fluoroquinolone antibiotics is postulated as a risk factor for
      subsequent development of type 2 diabetes. It is hypothesized that
      fluoroquinolones induce an intracellular magnesium deficit that can lead to
      insulin resistance. A temporal correlation is reported between the rate of
      outpatient prescription of quinolones and the incidence of diabetes during the
      period 1980-2011 with a lag of approximately two years (R(2)=0.86, P<10(-9)). The
      increase in incidence of diabetes after 1990 and the recent decrease in the
      number of new cases are both reflected in the fluoroquinolone prescription rates.
      A geographical correlation is reported (adj. R(2)=0.7, P<0.0001) between rates of
      increase in prevalence of diabetes in each U.S. state and a model using only
      local rates of outpatient fluoroquinolone prescription, local rates of increase
      in the prevalence of obesity, and local rates of population growth as predictor
      variables. Prescription rates of non-quinolone antibiotics correlated less well
      with the local rates of increase in prevalence of diabetes. The data are
      consistent with fluoroquinolone exposure predisposing an individual to develop
      diabetes with a probability that strongly depends upon factors that also lead to
      an increase in obesity. According to the hypothesis, much of the increase in the
      incidence of type 2 diabetes in the U.S. from 1990 to the present can be
      attributed to fluoroquinolone exposure. 

PMID- 24947194
TI  - Intra-articular pressures and joint mechanics: should we pay attention to
      effusion in knee osteoarthritis?
AB  - What factors play a role to ensure a knee joint does what it should given the
      demands of moving through the physical environment? This paper aims to probe the
      hypothesis that intra-articular joint pressures, once a topic of interest, have
      been left aside in contemporary frameworks in which we now view knee joint
      function. The focus on ligamentous deficiencies and the chondrocentric view of
      osteoarthritis, while important, have left little attention to the consideration
      of other factors that can impair joint function across the lifespan. Dynamic knee
      stability is required during every step we take. While there is much known about
      the role that passive structures and muscular activation play in maintaining a
      healthy knee joint, this framework does not account for the role that intra
      articular joint pressures may have in providing joint stability during motion and
      how these factors interact. Joint injuries invariably result in some form of
      intra-articular fluid accumulation. Ultimately, it may be how the knee
      mechanically responds to this fluid, of which pressure plays a significant role
      that provides the mechanisms for continued function. Do joint pressures provide
      an important foundation for maintaining knee function? This hypothesis is unique
      and argues that we are missing an important piece of the puzzle when attempting
      to understand implications that joint injury and disease have for joint function.

PMID- 24947195
TI  - Original hypothesis: Extracorporeal shockwaves as a homeostatic autoimmune
      restorative treatment (HART) for Type 1 diabetes mellitus.
AB  - Mononuclear invasion of Langerhans islet and the ensuing insulitis triggers
      signal-transduction for the autoimmune mediated pancreatic beta-cell (beta-cell)
      apoptosis that severely disrupts insulin production resulting in hyperglycemia
      associated with Type-1 diabetes (T1DM). Today extensive global research is being
      conducted to eliminate the need for insulin, and even prevent or find a cure for
      T1DM. The multifactorial combination of autoimmune dysfunction, Langerhans islet
      hypoxia, and bio-chemical disruption are seen to be contributory factors for beta
      cell destruction and the consequential disruption to insulin production.
      Regeneration of beta-cells back to physiological levels may restore homeostatic
      insulin levels, reversing T1DM. Evidence suggests that there are still
      functioning pancreatic beta-cells even in long standing T1DM providing the
      potential for their regeneration. Although the exact mechanism of extracorporeal
      shockwaves (ESW) is yet to be fully elucidated, it is seen to influence a complex
      spectrum of bio-chemical, cellular and neuronal functions (i.e. suppression of
      pro-inflammatory immune response, improved tissue hemodynamics, anti-microbial
      properties, and the induction of progenitor cell expression including
      proangiogenic factors and nitric oxide syntheses). The rationale for the use of
      ESW as a therapeutic modality in this instance is attributed to its restorative
      properties and safety profile demonstrated in urology, cardiology, chronic
      wounds, osteogenesis, complex pain syndromes, and tendinopathies. ESW may restore
      autoimmune homeostasis creating a suitable environment for pancreatic beta-cell
      proliferation which in-turn may significantly increase or normalize endogenous
      insulin secretion reducing or totally eliminating dependency of exogenous
      insulin. The devastating complications, morbidity and mortality associated with
      T1DM warrants the exploration of homeostatic autoimmune restorative treatment
      (HART) modalities that may partially or fully reverse this disease condition. We
      present our hypothesis discussing ESW as a potential homeostatic autoimmune
      restorative treatment (HART) option for T1DM. 

PMID- 24947196
TI  - Determination of GHB in human hair by HPLC-MS/MS: Development and validation of a
      method and application to a study group and three possible single exposure cases.
AB  - Gamma-hydroxybutyrate (GHB) over the last two decades has generated increased
      notoriety as a euphoric and disinhibiting drug of abuse in cases of drug-related
      sexual assault and for this reason it is considered a 'date rape' drug. The first
      aim of this paper was to develop and fully validate a method for the detection of
      GHB in human hair by high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) after liquid-liquid extraction (LLE). The second aim
      was the application of the method to hair samples of 30 GHB-free users in order
      to determine the basal level. The results obtained showed no significant
      differences in endogenous concentrations (p = 0.556) between hair samples of the
      three groups (black, blonde, and dyed hair) and the age and sex of the subjects
      did not affect the endogenous levels. Another 12 healthy volunteers, with no
      previous history of GHB use, were selected and a single dose (25 mg/Kg) was
      orally administered to all of them and hair samples were collected before the
      administration of the single dose and other two samples were collected one month
      and two months later, respectively. The segmental analysis of the latter two
      samples allowed us to calculate two ratios: 4.45:1 (95% C.I. 3.52-5.63) and
      3.35:1 (95% C.I. 2.14-5.18), respectively, which can be recommended as reasonable
      values for a positive identification of GHB intake. Finally the method was
      applied to three real cases where a GHB single exposure probably occurred.

PMID- 24947197
TI  - Purely cystic adrenal lesion in a newborn evolving into a solid neuroblastoma.
AB  - Purely cystic neuroblatomas are often discovered prenatally. As the main
      differential diagnosis is adrenal hemorrhage, follow-up sonography is warranted
      after birth. Cystic neuroblastomas are expected to evolve into lesions of mixed
      echogenicity with cystic and solid components. We present a rare case of a purely
      cystic left-sided adrenal lesion in a newborn, suggesting an adrenal hemorrhage,
      which on follow-up sonography evolved into a purely solid mass with poor
      vascularization, diagnosed as a cystic neuroblastoma. We suggest that even purely
      cystic adrenal masses in the newborn should be closely followed up with
      sonography, as they may represent purely cystic neuroblastomas.

PMID- 24947198
TI  - Minimal clinically important difference of the functional gait assessment in
      older adults.
AB  - BACKGROUND: The Functional Gait Assessment (FGA) is commonly used to measure
      walking balance. The minimal clinically important difference (MCID) has yet to be
      determined for the FGA. OBJECTIVE: The purposes of this study were to determine:
      (1) the MCID in the FGA for older community-dwelling adults relative to patients'
      and physical therapists' estimates of change and (2) the extent of agreement
      between patients' and physical therapists' estimates of change. DESIGN: This
      study was a prospective case series. METHODS: Patients and physical therapists
      rated the amount of change in balance while walking after an episode of physical
      therapy for balance retraining on a 15-point global rating of change (GROC)
      scale. Weighted kappa statistics were calculated to express agreement between
      patients' and physical therapists' GROC ratings. Functional Gait Assessment
      change scores were plotted on receiver operating characteristic curves. A cutoff
      of +3 on the GROC was the criterion used for important change. The optimal FGA
      change cutoff score for MCID was determined, and sensitivity (SN), specificity
      (SP), and likelihood ratios (LRs) were calculated. RESULTS: One hundred thirty
      five community-dwelling older adults (average age=78.8 years) and 14 physical
      therapists participated. There was poor agreement between the patients' and
      therapists' ratings of change (weighted kappa=.163). The estimated MCID value for
      the FGA using physical therapists' ratings of change as an anchor was 4 points
      (SN=0.66, SP=0.84, LR+=4.07, LR-=0.40). No accurate value for the FGA MCID could
      be determined based on the patients' ratings of change. LIMITATIONS: The small
      sample size was a limitation. CONCLUSION: Poor agreement between therapists' and
      patients' ratings indicate the need for further communication relative to patient
      goals. The 4-point MCID value for the FGA can be used for goal setting, tracking
      patient progress, and program evaluation.

PMID- 24947199
TI  - Coin rotation task: a valid test for manual dexterity in multiple sclerosis.
AB  - BACKGROUND: Impaired manual dexterity is frequent and disabling in people with
      multiple sclerosis (MS). Therefore, convenient, quick, and validated tests for
      manual dexterity in people with MS are needed. OBJECTIVE: The aim of this study
      was to validate the Coin Rotation Task (CRT) for examining manual dexterity in
      people with MS. DESIGN: This was a cross-sectional study. METHODS: A total of 101
      outpatients with MS were assessed with the CRT, the Expanded Disability Status
      Scale (EDSS), the Scale for the Assessment and Rating of Ataxia (SARA), and the
      Modified Ashworth Scale (MAS); muscle strength and sensory deficits of the hands
      were noted. The concurrent validity and diagnostic accuracy of the CRT were
      determined by comparison with the 9-Hole Peg Test (9HPT). Construct validity was
      determined by comparison with a valid dexterity questionnaire. Multiple
      regression analyses were done to explore correlations of the CRT with the EDSS,
      SARA, MAS, muscle strength, and sensory deficits. RESULTS: The CRT correlated
      significantly with the 9HPT (r=.73, P<.0001), indicating good concurrent
      validity. The cutoff values for the CRT relative to the 9HPT were 18.75 seconds
      for the dominant hand (sensitivity=81.5%, specificity=80.0%) and 19.25 seconds
      for the nondominant hand (sensitivity=90.3%, specificity=81.8%); these values
      indicated good diagnostic accuracy. Furthermore, the CRT correlated significantly
      with the dexterity questionnaire (r=-.49, P<.0001), indicating moderate construct
      validity. Multiple regression analyses revealed that the EDSS was the strongest
      predictor for impaired dexterity. LIMITATIONS: Most of the people examined had
      relapsing-remitting MS and EDSS scores of up to 7. CONCLUSIONS: This study
      validated the CRT as a test that can be used easily and quickly to evaluate
      manual dexterity in people with MS.

PMID- 24947200
TI  - The Breadth of Oral Health Research: Translating to Clinical Practice.

PMID- 24947201
TI  - Is Dysfunctional Use of the Mobile Phone a Behavioural Addiction? Confronting
      Symptom-Based Versus Process-Based Approaches.
AB  - Dysfunctional use of the mobile phone has often been conceptualized as a
      'behavioural addiction' that shares most features with drug addictions. In the
      current article, we challenge the clinical utility of the addiction model as
      applied to mobile phone overuse. We describe the case of a woman who overuses her
      mobile phone from two distinct approaches: (1) a symptom-based categorical
      approach inspired from the addiction model of dysfunctional mobile phone use and
      (2) a process-based approach resulting from an idiosyncratic clinical case
      conceptualization. In the case depicted here, the addiction model was shown to
      lead to standardized and non-relevant treatment, whereas the clinical case
      conceptualization allowed identification of specific psychological processes that
      can be targeted with specific, empirically based psychological interventions.
      This finding highlights that conceptualizing excessive behaviours (e.g., gambling
      and sex) within the addiction model can be a simplification of an individual's
      psychological functioning, offering only limited clinical relevance. KEY
      PRACTITIONER MESSAGE: The addiction model, applied to excessive behaviours (e.g.,
      gambling, sex and Internet-related activities) may lead to non-relevant
      standardized treatments. Clinical case conceptualization allowed identification
      of specific psychological processes that can be targeted with specific
      empirically based psychological interventions. The biomedical model might lead to
      the simplification of an individual's psychological functioning with limited
      clinical relevance.

PMID- 24947202
TI  - Estimating the density of femoral head trabecular bone from hip fracture patients
      using computed tomography scan data.
AB  - The purpose of this study was to compare computed tomography density (rhoCT )
      obtained using typical clinical computed tomography scan parameters to ash
      density (rhoash ), for the prediction of densities of femoral head trabecular
      bone from hip fracture patients. An experimental study was conducted to
      investigate the relationships between rhoash and rhoCT and between each of these
      densities and rhobulk and rhodry . Seven human femoral heads from hip fracture
      patients were computed tomography-scanned ex vivo, and 76 cylindrical trabecular
      bone specimens were collected. Computed tomography density was computed from
      computed tomography images by using a calibration Hounsfield units-based
      equation, whereas rhobulk, rhodry and rhoash were determined experimentally. A
      large variation was found in the mean Hounsfield units of the bone cores (HUcore)
      with a constant bias from rhoCT to rhoash of 42.5 mg/cm3. Computed tomography and
      ash densities were linearly correlated (R 2 = 0.55, p < 0.001). It was
      demonstrated that rhoash provided a good estimate of rhobulk (R 2 = 0.78, p <
      0.001) and is a strong predictor of rhodry (R 2 = 0.99, p < 0.001). In addition,
      the rhoCT was linearly related to rhobulk (R 2 = 0.43, p < 0.001) and rhodry (R 2
      = 0.56, p < 0.001). In conclusion, mineral density was an appropriate predictor
      of rhobulk and rhodry , and rhoCT was not a surrogate for rhoash . There were
      linear relationships between rhoCT and physical densities; however, following the
      experimental protocols of this study to determine rhoCT , considerable scatter
      was present in the rhoCT relationships.

PMID- 24947203
TI  - N-terminal Pro-B type natriuretic peptide as long-term predictor of death after
      an acute pulmonary embolism.
AB  - BACKGROUND AND OBJECTIVE: After an acute pulmonary embolism few long-term
      prognostic factors have shown to be of practical use. We hypothesized that, as in
      heart failure, natriuretic peptides could serve as biomarkers of a late
      deleterious prognosis. PATIENTS AND METHODS: Consecutive patients admitted to an
      Internal Medicine ward diagnosed with acute pulmonary embolism were traced
      through the computerized system of clinical episodes of Navarra Health System and
      by telephone calls. On hospitalization, standard evaluation was made, previous
      history of cancer and cardiac disease was recorded, and N-terminal ProB-type
      natriuretic peptide (NT-ProBNP), D-dimer and Troponin I were measured. In the
      analysis all-causes death was considered. RESULTS: Two hundred and thirty-four
      patients were traced, median age 75 [interquartile range (IQR) 16] years old,
      women 51%. At a median time of 9.5 (IQR 29) months 52 (22%) patients had died, 38
      (73%) dead patients had NT-ProBNP higher than 850 ng/L. NT-ProBNP in dead
      patients was 2.741 (IQR 7.420)ng/L and 662 (IQR 2.517)ng/L in survivors
      (p<0.001). Age (OR 4.37 CI 95% 1.04-1.16) and NT-ProBNP (OR 1.49 CI 95% 1-1.002)
      showed to be independent factors of mortality. Between the 3rd and 20th month
      after the diagnosis, a level of NT-ProBNP higher than 850 ng/L (sensitivity 0.86,
      specificity 0.45 and negative predictive value 0.92) was associated with a lower
      survival (p=0.019), hazard ratio 1.89, OR 7.67 (CI 95% 1.52-39.44) for this
      period. CONCLUSION: Besides the unchangeable age, plasma level of NT-ProBNP
      measured on acute pulmonary embolism could predict longer-term all-cause death.

PMID- 24947204
TI  - [Dermatitis herpetiformis].

PMID- 24947205
TI  - Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical
      and pathological correlates.
AB  - Gaucher disease (GD) is a lysosomal storage disorder characterized by
      accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a
      result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone
      complications are an important cause of morbidity of GD and are thought to result
      from imbalance in bone remodeling. Bone manifestations among GD patients
      demonstrate a large variation including increased osteoclastic bone resorption,
      low bone formation and osteonecrosis. The purpose of the current case series is
      to describe the histological features observed in undecalcified bone samples,
      obtained from three GD patients, and evaluate the relationship with clinical
      features in these patients. Bone fragments were obtained from three adult type 1
      GD patients with variable degrees of bone disease during orthopedic surgery.
      Specimens were embedded without prior decalcification in methylmethacrylate and
      prepared for histology according to standardized laboratory procedures. Histology
      revealed a heterogeneous pattern of bone involvement. High cellularity of bone
      marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed
      in a patient with a history of multiple bone complications, while minimal bone
      turnover and few GCs were detected in the mildest affected patient in this
      series. An intermediate picture with relatively low bone turnover and a
      substantial amount of Gaucher cells was demonstrated in the third, moderately
      affected patient. No gross abnormalities in three biochemical markers of bone
      turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1
      collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent
      Goldner and TRAP staining offered a unique possibility to study bone histological
      findings in GD. Our data show that bone manifestations in GD may vary both
      clinically as well as histologically and bone disease in GD will likely require a
      personalized approach. 

PMID- 24947206
TI  - Genomic comparison of chitinolytic enzyme systems from terrestrial and aquatic
      bacteria.
AB  - Chitin degradation ability is known for many aquatic and terrestrial bacterial
      species. However, differences in the composition of chitin resources between
      aquatic (mainly exoskeletons of crustaceans) and terrestrial (mainly fungal cell
      walls) habitats may have resulted in adaptation of chitinolytic enzyme systems to
      the prevalent resources. We screened publicly available terrestrial and aquatic
      chitinase-containing bacterial genomes for possible differences in the
      composition of their chitinolytic enzyme systems. The results show significant
      differences between terrestrial and aquatic bacterial genomes in the modular
      composition of chitinases (i.e. presence of different types of carbohydrate
      binding modules). Terrestrial Actinobacteria appear to be best adapted to use a
      wide variety of chitin resources as they have the highest number of chitinase
      genes, the highest diversity of associated carbohydrate-binding modules and the
      highest number of CBM33-type lytic polysaccharide monooxygenases. Actinobacteria
      do also have the highest fraction of genomes containing beta-1, 3-glucanases,
      enzymes that may reinforce the potential for degrading fungal cell walls. The
      fraction of bacterial chitinase-containing genomes encoding polyketide synthases
      was much higher for terrestrial bacteria than for aquatic ones supporting the
      idea that the combined production of antibiotics and cell-wall degrading
      chitinases can be an important strategy in antagonistic interactions with fungi. 

PMID- 24947207
TI  - Novel membrane-associated prostaglandin E synthase-2 from crustacean arthropods.
AB  - Prostaglandins (PG) have been shown to play important physiological roles in
      insects and marine invertebrates, yet the knowledge of their biosynthetic
      pathways is often lacking. Recently, we described cyclooxygenases in two amphipod
      crustaceans, Gammarus sp. and Caprella sp. In the present study, we report the
      cloning and characterization of prostaglandin E synthases (PGES) from the same
      organisms. The amphipod membrane-bound PGES-2-type enzymes share about 40% of the
      amino acid sequence identity with human mPGES-2, contain a conserved Cys110-x-x
      Cys113 motif and have very low heme-binding affinity. The recombinant enzymes
      purified in the absence of dithiothreitol specifically catalyze the isomerization
      of PGH2 into PGE2. The PGES activity is increased in the presence of reduced
      glutathione and inhibited with a sulfhydryl group inhibitor. We assume that the
      amphipod mPGES-2, unlike in their mammalian counterparts, is responsible for PGE2
      synthesis, not only in vitro but also in vivo. 

PMID- 24947208
TI  - Evaluation of chitinolytic activities and membrane integrity in gut tissues of
      Arctic charr (Salvelinus alpinus) fed fish meal and zygomycete biomass.
AB  - Chitinolytic activity, nutrient uptake and intestinal barrier functions were
      investigated in gut tissues of Arctic charr (Salvelinus alpinus) fed iso
      nitrogenous diets based on fish meal, with or without inclusion of zygomycetes
      (Rhizopus oryzae). We found that gut tissue of Arctic charr had significant
      chitinase activity, of both endo- and exo-chitinase iso-forms. Moreover, the
      distribution pattern along the GI tract of Arctic charr differed between endo
      chitinase and exo-chitinase. The endo-chitinase activity in stomach tissue and in
      the distal intestine was several hundred-fold higher than the exo-chitinase
      activity in stomach tissue. The greatest exo-chitinase activity was found in the
      distal intestine. The zygomycete-based diet resulted in higher chitinolytic
      activity in gut tissue compared to the fish meal-based diet. Disturbed intestinal
      integrity and increased uptake rate of the amino acid lysine were observed in the
      distal, but not proximal, intestine of fish fed the zygomycete-based feed. 

PMID- 24947209
TI  - Molecular characterization and transcriptional regulation of the Na +/K+ ATPase
      alpha subunit isoforms during development and salinity challenge in a teleost
      fish, the Senegalese sole (Solea senegalensis).
AB  - In the present work, five genes encoding different Na(+),K(+) ATPase (NKA) alpha
      isoforms in the teleost Solea senegalensis are described for the first time.
      Sequence analysis of predicted polypeptides revealed a high degree of
      conservation across teleosts and mammals. Phylogenetic analysis clustered the
      five genes into three main clades: alpha1 (designated atp1a1a and atp1a1b),
      alpha2 (designated atp1a2) and alpha3 (designated atp1a3a and atp1a3b) isoforms.
      Transcriptional analysis in larvae showed distinct expression profiles during
      development. In juvenile tissues, the atp1a1a gene was highly expressed in
      osmoregulatory organs, atp1a2 in skeletal muscle, atp1a1b in brain and heart and
      atp1a3a and atp1a3b mainly in brain. Quantification of mRNA abundance after a
      salinity challenge showed that atp1a1a transcript levels increased significantly
      in the gill of soles transferred to high salinity water (60 ppt). In contrast,
      atp1a3a transcripts increased at low salinity (5 ppt). In situ hybridization
      (ISH) analysis revealed that the number of ionocytes expressing atp1a1a
      transcripts in the primary gill filaments was higher at 35 and 60 ppt than at 5
      ppt and remained undetectable or at very low levels in the lamellae at 5 and 35
      ppt but increased at 60 ppt. Immunohistochemistry showed a higher number of
      positive cells in the lamellae. Whole-mount analysis of atp1a1a mRNA in young
      sole larvae revealed that it was localized in gut, pronephric tubule, gill, otic
      vesicle, yolk sac ionocytes and chordacentrum. Moreover, atp1a1a mRNAs increased
      at mouth opening (3 DPH) in larvae incubated at 36 ppt with a greater signal in
      gills.

PMID- 24947210
TI  - Expression pattern of heme oxygenase 1 gene and hypoxic adaptation in chicken
      embryos.
AB  - Heme oxygenase 1 (HO-1), a rate-limiting enzyme of heme catabolism, has a crucial
      role of cytoprotective functions under hypoxia. The objective of the present
      study was to investigate potential differences in protective effect of HO-1 gene
      on chicken (Gallus gallus) embryo lung during late incubation. At embryonic day
      (D) D16, D18, D19, and D20 of incubation, the expression of HO-1 in the lungs of
      chicken embryos (Tibet and Shouguang chickens) incubated in normoxic (21% O2) and
      hypoxic (13% O2) conditions was measured. SNPs were screened within 5'-flanking
      region and coding regions with PCR-sequencing and the genotype of the SNPs was
      determined with PCR-RFLP in Tibet, Chahua and Shouguang chicken populations. In
      conclusion, the Tibet chicken had higher HO-1 expression on D19 under hypoxic
      incubation and had two SNPs with different frequency distributions from other
      chicken breeds, which might be a way that the Tibet chicken had hereditary
      adaptation to hypoxia during embryonic development. 

PMID- 24947212
TI  - Revisiting the multigene families: Plasmodium var and vir genes.
AB  - Malaria is an infectious disease that is widespread in tropical and subtropical
      regions. The malaria parasite is able to skip the host immunity and thus
      maintains not only persistent but also repeated infections. There are a number of
      multigene families in Plasmodium that code for the variant antigens and are
      targets for protective immunity. In this article, we summarize the virulence
      genes of P. falciparum (var genes) and P. vivax (vir genes) which play key roles
      in disease pathogenesis by evading elimination by the host immune system. These
      genes occurring within the parasite population are mostly present in the
      subtelomeric regions of the chromosome. 

PMID- 24947211
TI  - Bioactivity studies on atypical natural opioid hexapeptides processed from
      proenkephalin (PENK) precursor polypeptides.
AB  - Endogenous opioids are derived from four related polypeptide precursors:
      proenkephalin (PENK), prodynorphin (PDYN), pronociceptin (PNOC) and
      proopiomelanocortin (POMC). In mammals PENK encodes for four copy of Met
      enkephalin, one octapeptide Met-enkephalin-Arg-Gly-Leu, one heptapeptide Met
      enkephalin-Arg-Phe and a single copy of Leu-enkephalin. Our detailed
      bioinformatic search on the existing PENK sequences revealed several atypical
      hexapeptide Met-enkephalins in different vertebrate animals. They are located
      either in the second enkephalin unit or in the seventh enkephalin core position
      at the C-terminus. Altogether four different hexapeptide sequences were obtained
      representing eleven animal species: Met-enkephalin-Arg(6) (YGGFMR) in the bird
      zebra finch, Met-enkephalin-Asp(6) (YGGFMD), Met-enkephalin-Ile(6) (YGGFMI) in
      zebrafish; and Met-enkephalin-Ser(6) (YGGFMS) in two pufferfish species. All
      novel peptides were chemically synthesized and studied in receptor binding and G
      protein activation assays performed on rat brain membranes. The four novel
      enkephalins were equipotent in stimulating G-proteins. Affinities of the peptides
      determined by equilibrium competition assays in receptor binding experiments were
      statistically different. At the MOP receptors the highest affinity (Ki 4nM) was
      obtained with the zebra finch peptide Met-enkephalin-Arg(6). The pufferfish Met
      enkephalin-Ser(6) exhibited the highest affinity (Ki 6.7nM) at the DOP receptor.
      Phylogenetic neuropeptide libraries, defined here as a collection of mutationally
      different species variants of orthologous and paralogous peptide sequences,
      represent the natural molecular diversity of the neuropeptides. Such libraries
      can provide a wide range of structural information establishing comparative
      functional analyses. Since DNA sequencing data are rapidly increasing, more
      development in the natural peptide library concept is expected. 

PMID- 24947213
TI  - DENVirDB: a web portal of dengue virus sequence information on Asian isolates.
AB  - DENVirDB is a web portal that provides the sequence information and
      computationally curated information of dengue viral proteins. The advent of
      genomic technology has increased the sequences available in the public databases.
      In order to create relevant concise information on Dengue Virus (DENV), the
      genomic sequences were collected, analysed with the bioinformatics tools and
      presented as DENVirDB. It provides the comprehensive information of complete
      genome sequences of dengue virus isolates of Southeast Asia, viz. India,
      Bangladesh, Sri Lanka, East Timor, Philippines, Malaysia, Papua New Guinea,
      Brunei and China. DENVirDB also includes the structural and non-structural
      protein sequences of DENV. It intends to provide the integrated information on
      the physicochemical properties, topology, secondary structure, domain and
      structural properties for each protein sequences. It contains over 99 entries in
      complete genome sequences and 990 entries in protein sequences, respectively.
      Therefore, DENVirDB could serve as a user friendly database for researchers in
      acquiring sequences and proteomic information in one platform. 

PMID- 24947214
TI  - Phlebotomus sergenti a common vector of Leishmania tropica and Toscana virus in
      Morocco.
AB  - BACKGROUND & OBJECTIVES: An entomological study using CDC miniature light-traps
      was performed in El Hanchane locality, where cutaneous leishmaniasis (CL) was
      emerging during the summer of 2011. The aim of this study is to identify the
      vectors of Leishmania and of phleboviruses. METHODS: In the field, a total of 643
      sandfly specimens were collected, identified by morphological keys and
      categorized by sex and species. A total of nine distinct species were
      morphologically identified where seven belonged to the Phlebotomus genus and two
      species to the Sergentomyia genus. Phlebotomus sergenti was the most abundant
      species (76%). Phleboviruses were detected by nested RT-PCR using 30 pooled
      sandflies while P. sergenti females were tested individually for infections of
      Leishmania species. RESULTS: By using ITS1-PCR-RFLP approach, Leishmania tropica
      DNA was detected in 10 females, caught in this emerging focus, and provide
      additional evidence in favour of the role of P. sergenti as vector of L. tropica
      in Morocco. Real-time PCR screening for phlebovirus RNA, using an assay targeting
      the polymerase gene, showed positive result in one pool of male P. sergenti.
      INTERPRETATION & CONCLUSION: In this study, P. sergenti were infected by L.
      tropica and Toscana virus. To our knowledge, actually this is the first time that
      Toscana virus has been detected in P. sergenti.

PMID- 24947215
TI  - Spatial density of Aedes distribution in urban areas: a case study of breteau
      index in Kuala Lumpur, Malaysia.
AB  - BACKGROUND & OBJECTIVES: Dengue fever (DF) is a major vector-borne disease in
      Malaysia. The incidences of DF in Malaysia are caused by viruses transmitted
      through the bites of infected female Aedes albopictus and Ae. aegypti mosquitoes.
      This study aims to establish the spatial density of mosquito population or
      breteau index (BI) in the areas of Kuala Lumpur using geographic information
      system (GIS), remote sensing (RS) and spatial statistical tools. METHOD: The 2010
      weekly report data of BI obtained from the Ministry of Health (MoH) and the 2010
      monthly rainfall data obtained from Malaysia Meteorological Services Department
      were analyzed using RS and spatial statistical tools to show the spatial
      correlation of dengue in each zone in Kuala Lumpur. The Kernel density was
      implemented to identify the better dengue hotspot localities. RESULTS: RESULTS
      indicated a strong significant positive relationship between the number of
      localities with high BI and monthly rainfall (r = 0.64; p = 0.024). In addition,
      types of landuse did not appear to influence the mosquito's population (Built-up:
      r = 0.16, p = 0.118; Cleared area: r = - 0.107, p = 0.304; Vegetation dense: r = 
      0.206, p = 0.046; Vegetation sparse: r = 0.023, p = 0.823; and Water: r = 0.246,
      p = 0.016). INTERPRETATION & CONCLUSION: In the present study, several hotspots
      identified will be beneficial to assist the local health authorities to reduce
      and eradicate mosquitoes in these areas. These results will provide valuable
      information through the application of advanced tools in combating Aedes
      mosquitoes.

PMID- 24947216
TI  - Differential expression of glutathione s-transferase enzyme in different life
      stages of various insecticide-resistant strains of Anopheles stephensi: a malaria
      vector.
AB  - BACKGROUND & OBJECTIVES: Interest in insect glutathione s-transferases (GSTs) has
      primarily focused on their role in insecticide resistance. These play an
      important role in biotransformation and detoxification of many different
      xenobiotic and endogenous substances including insecticides. The GST activity
      among 10 laboratory selected insecticide resistant and susceptible/control
      strains of Anopheles stephensi was compared using the substrates 1-chloro-2,4
      dinitrobenzene (CDNB). The difference in the GST activities of different life
      stages of diverse insecticide resistant strains was compared and presented.
      METHODS: About 100 larvae, pupae, adult males, adult females and eggs (100 MUg in
      total weight) were collected and used for the experiment. The extracts were
      prepared from each of the insecticide-resistant strains and control. Protein
      contents of the enzyme homogenate and GST activities were determined. RESULTS:
      Deltamethrin and cyfluthrin-resistant strains of An. stephensi showed
      significantly higher GST activity. Larvae and pupae of DDT-resistant strain
      showed peak GST activity followed by the propoxur-resistant strain. On contrary,
      the GST activity was found in reduced quantity in alphamethrin, bifenthrin,
      carbofuran and chloropyrifos resistant strains. Adults of either sexes showed
      higher GST activity in mosquito strain resistant to organophosphate group of
      insecticides namely, temephos and chloropyrifos. INTERPRETATION & CONCLUSION: The
      GST activity was closely associated with almost all of the insecticides used in
      the study, strengthening the fact that one of the mechanisms associated with
      resistance includes an increase of GST activity. This comparative data on GST
      activity in An. stephensi can be useful database to identify possible underlying
      mechanisms governing insecticide-resistance by GSTs.

PMID- 24947217
TI  - Insecticidal compounds from Rhizophoraceae mangrove plants for the management of
      dengue vector Aedes aegypti.
AB  - BACKGROUND & OBJECTIVES: Mosquito control is facing a threat due to the emergence
      of resistance to synthetic insecticides. Insecticides of botanical origin could
      serve as potential alternatives in future. Larvicidal efficacies of different
      parts of mangrove plants belonging to Rhizophoraceae family were tested against
      the late IV instar larvae of dengue vector, Aedes aegypti. METHODS: Different
      plant parts (leaf, bark, root, stilt root, hypocotyl and flower) of
      Rhizophoraceae family mangrove plants (Bruguiera cylindrica, Ceriops decandra,
      Rhizophora mucronata and R. apiculata) were collected from Karangadu southeast
      coast of India. The larval mortality was observed after 24 h exposure. Repellency
      bioassays were carried out in a 10 Chi 10 Chi 3 m room at 27- 35 degrees C and 60
      80% RH. The bark (A3 and E1) and stilt root (A3 and E4) fractions of R.
      mucronata with different concentrations (0.25, 0.50, 0.75, 1, 2 and 4 mg/cm) were
      applied on one arm. RESULTS: The stilt root crude extract of R. mucronata showed
      maximum larvicidal activity (LC50 value 0.0275 +/- 0.0066 MUg/ml and LC90 =
      0.0695 +/- 0.156 MUg/ml) followed by the bark extract (LC50 value of 0.03 +/-
      0.0076 MUg/ml and LC90 = 0.0915 +/- 0.156 MUg/ml). Column chromatographic
      fractions of R. mucronata bark extracts (E1) showed maximum larvicidal activity
      (LC50 = 0.0496 +/- 0.0085 MUg/ml and LC90 = 0.1264 +/- 0.052 MUg/ml) followed by
      the acetone extract (LC50 = 0.0564 +/- 0.0069 MUg/ml and LC90 = 0.1187 +/- 0.05
      MUg/ml). Ethanolic fraction (E4) of R. mucronata stilt root extracts showed
      maximum larvicidal activity (LC50 = 0.0484 +/- 0.0078 MUg/ml and LC90 = 0.1191 +/
      0.025 MUg/ml) followed by acetone fraction (A3) (LC50 = 0.0419 +/- 0.0059 MUg/ml
      and LC90 = 0.0955 +/- 0.069 MUg/ml). Repellent activity of R. mucronata stilt
      root and bark extracts (A3) showed maximum percentage of protection (97.5%) with
      9.1 h protection time at 4 mg concentration of the stilt root extract. Moreover,
      ethanolic fraction of the stilt root (E4) extract showed maximum percentage of
      protection (100%) with 10 h protection time at 4 mg concentration. GC-MS analysis
      revealed that R. mucronata possesses variety of biopesticidal compounds.
      INTERPRETATION & CONCLUSION: The results as well as the significance of this
      preliminary investigation highlight the importance of R. mucronata as a novel
      source for natural insecticidal products.

PMID- 24947218
TI  - Emerging new trends of malaria in children: a study from a tertiary care centre
      in northern India.
AB  - BACKGROUND & OBJECTIVES: Vivax malaria has long been considered a benign entity.
      However, an increasing number of reports are highlighting that it may no longer
      be so. An investigation was carried out to study the profile of malarial
      admissions in a tertiary care pediatric hospital and to analyse the burden of
      vivax-related complications. METHODS: It is a retrospective observational study.
      The medical case records of all the patients admitted in the year 2011 with the
      clinical diagnosis of malaria and laboratory evidence in the form of positive
      peripheral smear and/or rapid malarial antigen test were retrieved and
      retrospectively analysed. RESULTS: Overall, 198 cases were included, 128 (64.6%)
      were due to Plasmodium vivax, 66 (33.3%) due to P. falciparum and 4 (2%) had
      evidence of mixed infection of Pv + Pf. The clinical features on admission were
      similar in all the groups. In total, 64/128 (50%) patients with vivax infection
      had one or more complications with severe anemia in 33 (26%) and cerebral malaria
      in 16 (12.5%). Six deaths were reported in P. vivax cases. In the falciparum
      group, 52 (78.8%) had one or more complications with severe anemia in 37 (56.1%)
      and cerebral malaria in 24 (36.4%). Four deaths were reported in P. falciparum
      cases. INTERPRETATION & CONCLUSION: Overall because of their larger numbers,
      vivax patients outnumbered other groups, with regards to severe complications and
      deaths. It was concluded that vivax malaria is emerging as an important cause of
      malaria-related complications in children.

PMID- 24947219
TI  - Knowledge, attitudes and practices of malaria control among communities from the
      health district of Forecariah in the Republic of Guinea, West Africa.
AB  - BACKGROUND & OBJECTIVES: Malaria is the leading cause of death in children under
      5-yr of age in the Republic of Guinea. This study aimed at investigating the
      knowledge, attitudes and practices of malaria control in urban and rural
      communities in Guinea in order to better target future health interventions.
      METHODS: A cross-sectional survey of 200 randomly selected households was
      conducted in an urban site and in three rural villages within the health district
      of Foriotacariah using two semi-structured questionnaires. RESULTS: Only 18.5% of
      the respondents were aware of the role of mosquitoes in the transmission of
      malaria in both urban and rural households. Mosquito nets were identified as a
      malaria prevention method by 11.5% of the participants and only 8.5% of the
      respondents mentioned stagnant water as a potential mosquito breeding site.
      Households' heads were more aware of mosquito control methods, with 56 and 42% of
      the respondents recognizing that bednets or insecticidal coils can protect from
      mosquitoes, respectively. Despite the limited knowledge of malaria transmission
      and prevention, 55% of the households owned at least one long-lasting insecticide
      treated net (LLIN) and 79% of the net-owning households slept under a net/LLIN
      the night before the survey. INTERPRETATION & CONCLUSION: In order to maximize
      the benefits of malaria control strategies, health education should be
      implemented, building on the higher awareness of mosquito control methods and
      stressing the role of vectors in transmitting the disease.

PMID- 24947220
TI  - High prevalence of asymptomatic malaria in apparently healthy schoolchildren in
      Aliero, Kebbi state, Nigeria.
AB  - BACKGROUND & OBJECTIVES: In malaria endemic areas, continuous exposure to
      Plasmodium parasites leads to asymptomatic carriers that provide a reservoir,
      contributing to the persistence of malaria transmission. Thus, a study of the
      degree of prevalence of asymptomatic parasitaemias will help in assessing the
      level of reservoir of infection. METHODS: All the consented participants without
      any signs and symptoms, suggestive of malaria were interviewed and thick blood
      smears were made to detect malaria parasites. The children presenting with
      malaria or any other severe illness, and those declining to give consent were
      excluded from the study. RESULTS: A total of 118 (59.6%) children out of 198
      apparently healthy children were positive for malaria parasites while 80 (40.4%)
      children were negative for malaria parasites. Prevalence of asymptomatic malaria
      was higher in males 75 (63.6%) compared to females 43 (36.4%), but the difference
      was not statistically significant. Incidence of asymptomatic malaria was highest
      with 76.1% in the children aged 6- 10 yr. There was statistically significant
      association of the use of bednet on prevalence of asymptomatic malaria.
      INTERPRETATION & CONCLUSION: High prevalence of asymptomatic malaria detected in
      this study is a big challenge and can be a threat to the present malaria control
      programme. Thus, it should be considered in assessing and reorganising more
      effective malaria elimination strategies to achieve the desired goal of malaria
      control.

PMID- 24947221
TI  - Insecticide resistance and human blood meal preference of Anopheles annularis in
      Asom-Meghalaya border area, northeast India.

PMID- 24947222
TI  - Bacterial groups associated with Nyssomyia neivai (Diptera: Psychodidae)
      sandflies.

PMID- 24947223
TI  - A multidisciplinary approach to an uncommon case of laryngeal leishmaniasis in
      Turkey.

PMID- 24947224
TI  - Hemophagocytic syndrome in Plasmodium vivax malaria.

PMID- 24947225
TI  - "Collateral" effect of artemether in an atypical kidney involvement by Plasmodium
      falciparum malaria: a case report.

PMID- 24947226
TI  - Plasmodium malariae infection: a case of missed diagnosis.

PMID- 24947227
TI  - Joint estimation of chemical shift and quantitative susceptibility mapping
      (chemical QSM).
AB  - PURPOSE: The purpose of this work is to address the unsolved problem of
      quantitative susceptibility mapping (QSM) of tissue with fat where both fat and
      susceptibility change the MR signal phase. THEORY AND METHODS: The chemical shift
      of fat was treated as an additional unknown and was estimated jointly with
      susceptibility to provide the best data fitting using an automated and iterative
      algorithm. A simplified susceptibility model was used to calculate an updated
      value of the chemical shift based on the local magnetic field in each iteration.
      Numerical simulation, phantom experiments and in vivo imaging were performed.
      Artifacts were assessed by measuring the susceptibility variance in uniform
      regions. Accuracy was assessed by comparison with ground truth in simulation, and
      using a susceptibility matching approach in phantom. RESULTS: Using the proposed
      method, artifacts on the QSM image were markedly suppressed in all tested
      datasets compared with results generated using fixed chemical shifts. Accuracy of
      the estimated susceptibility was also improved in numerical simulation and
      phantom experiments. CONCLUSION: A joint estimation of fat content and magnetic
      susceptibility using an iterative chemical shift update was shown to improve
      image quality and accuracy on QSM images.

PMID- 24947228
TI  - Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and
      antibacterial ability of titanium.
AB  - Zinc (Zn) and silver (Ag) are co-implanted into titanium by plasma immersion ion
      implantation. A Zn containing film with Ag nanoparticles (Ag NPs) possessing a
      wide size distribution is formed on the surface and the corrosion resistance is
      improved due to the micro-galvanic couples formed by the implanted Zn and Ag. Not
      only are the initial adhesion, spreading, proliferation and osteogenic
      differentiation of rBMSCs observed from the Zn/Ag implanted Ti in vitro, but also
      bacteria killing is achieved both in vitro and in vivo. Electrochemical
      polarization and ion release measurements suggest that the excellent osteogenic
      activity and antibacterial ability of the Zn/Ag co-implanted titanium are related
      to the synergistic effect resulting from the long-range interactions of the
      released Zn ions and short-range interactions of the embedded Ag NPs. The Zn/Ag
      co-implanted titanium offers both excellent osteogenic activity and antibacterial
      ability and has large potential in orthopedic and dental implants. 

PMID- 24947229
TI  - Hyaluronic acid-decorated reconstituted high density lipoprotein targeting
      atherosclerotic lesions.
AB  - The primary aim of our current study was to utilize hyaluronic acid (HA) to
      decorate reconstituted high density lipoprotein (rHDL) loaded with lovastatin
      (LT), termed as HA-LT-rHDL, in order to investigate whether coating HA could
      efficiently evade from the undesired uptake of LT-rHDL in liver mediated by
      scavenger receptor class B type I (SR-BI) and then greatly accumulate LT-rHDL in
      atherosclerotic lesions via strong HA affinity to CD44 up-regulated at
      inflammatory sites such as atherosclerotic lesions, thus exerting enhanced
      atheroprotective efficacy. In vitro characterizations indicated the successful HA
      decoration onto the surface of LT-rHDL, which could be indirectly verified by the
      increased particle size, enhanced negative surface charge and reduced in vitro
      drug release rate after HA decoration. Compared with rHDL without HA, HA
      decoration endowed rHDL with better atherosclerotic lesions targeting efficiency
      and lower liver accumulation, proved by results from ex vivo imaging and tissue
      distribution. Furthermore, atheroprotective efficacy in model animal showed that
      HA-LT-rHDL had the best potent efficacy than other LT preparations, which was
      demonstrated by the fewest atherosclerotic lesions sizes, the most minimum mean
      intima-media thickness (MIT), the lowest macrophage infiltration and expression
      of matrix metalloproteinase-9 (MMP-9), respectively. Above results demonstrated
      that the newly designed HA-LT-rHDL could decrease the non-targeted uptake by
      liver and deliver a large amount of drug into atherosclerotic lesions so as to
      efficiently suppress the advancement of atherosclerosis. 

PMID- 24947230
TI  - The potential role of free chitosan in bone trauma and bone cancer management.
AB  - Bone defects caused by fractures or cancer-mediated destruction are debilitating.
      Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a
      free drug. We demonstrate that free chitosan promotes osteoblast proliferation
      and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I
      expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of
      endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing
      of bone fractures with greater trabecular bone formation was observed in mice
      treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and
      breast cancer cells via caspase-2 and -3 activation, and reduces their
      establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not
      their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery
      of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour
      in pregnant mice, but decreases foetal length and changes pancreatic secretory
      acini. With certain controls in place, chitosan could be useful for bone trauma
      management. 

PMID- 24947231
TI  - Quantitative control of active targeting of nanocarriers to tumor cells through
      optimization of folate ligand density.
AB  - The active targeting delivery system has been widely studied in cancer therapy by
      utilizing folate (FA) ligands to generate specific interaction between
      nanocarriers and folate receptors (FRs) on tumor cell. However, there is little
      work that has been published to investigate the influence of the definite density
      of the FA ligands on the active targeting of nanocarriers. In this study, we have
      combined magnetic-guided iron oxide nanoparticles with FA ligands, adjusted the
      FA ligand density and then studied the resulting effects on the active targeting
      ability of this dual-targeting drug delivery system to tumor cells. We have also
      optimized the FA ligand density of the drug delivery system for their active
      targeting to FR-overexpressing tumor cells in vitro. Prussian blue staining, semi
      thin section of cells observed with transmission electron microscopy (TEM) and
      inductively coupled plasma-atomic emission spectroscopy (ICP-AES) have shown that
      the optimal FA density is from 2.3 * 10(18) to 2.5 * 10(18) per gram
      nanoparticles ((g.NPs)(-1)). We have further tried to qualitatively and
      quantitatively control the active targeting and delivering of drugs to tumors on
      4T1-bearing BALB/c mice. As expected, the in vivo experimental results have also
      demonstrated that the FA density of the magnetic nanoparticles (MNPs) could be
      optimized for a more easily binding to tumor cells via the multivalent linkages
      and more readily internalization through the FR-mediated endocytosis. Our study
      can provide a strategy to quantitatively control the active targeting of
      nanocarriers to tumor cells for cancer therapy. 

PMID- 24947232
TI  - Enhancing therapeutic efficacy through designed aggregation of nanoparticles.
AB  - Particle size is a key determinant of biological performance of sub-micron size
      delivery systems. Previous studies investigating the effect of particle size have
      primarily focused on well-dispersed nanoparticles. However, inorganic
      nanoparticles are prone to aggregation in biological environments. In our
      studies, we examined the consequence of aggregation on superparamagnetic iron
      oxide (SPIO) nanoparticle-induced magnetic hyperthermia. Here we show that the
      extent and mechanism of hyperthermia-induced cell kill is highly dependent on the
      aggregation state of SPIO nanoparticles. Well-dispersed nanoparticles induced
      apoptosis, similar to that observed with conventional hyperthermia. Sub-micron
      size aggregates, on the other hand, induced temperature-dependent autophagy
      through generation of oxidative stress. Micron size aggregates caused rapid
      membrane damage, resulting in acute cell kill. Overall, this work highlights the
      potential for developing highly effective anticancer therapeutics through
      designed aggregation of nano delivery systems. 

PMID- 24947234
TI  - Role of chemoradiotherapy in oesophageal cancer -- adjuvant and neoadjuvant
      therapy.
AB  - Despite low postoperative mortality rates, the long-term outcomes from surgical
      based treatment for oesophageal cancer remain poor. Chemoradiotherapy (CRT),
      either given before surgical resection as neoadjuvant therapy or after resection
      as adjuvant therapy, has been postulated to improve these outcomes. This
      systematic review examines the evidence for these approaches. The evidence for
      postoperative radiotherapy is limited and conclusions are difficult, but it may
      have a role in patients at high risk of local relapse (positive margins). The
      addition of chemotherapy is recommended when possible. Patient selection is
      important due to the associated toxicities. The evidence for neoadjuvant
      treatment is stronger and based on the current evidence neoadjuvant CRT can be
      recommended as a treatment approach in T2-T4, N1-3 oesophageal cancer for both
      adenocarcinoma and squamous cell carcinoma, but further work is needed to
      establish its superiority over neoadjuvant chemotherapy alone, particularly for
      adenocarcinoma. We recommend that further studies divide the two histologies and
      they should be treated as two separate diseases. 

PMID- 24947235
TI  - Functional architecture of the cell's nucleus in development, aging, and disease.
AB  - In eukaryotes, the function of the cell's nucleus has primarily been considered
      to be the repository for the organism's genome. However, this rather simplistic
      view is undergoing a major shift, as it is increasingly apparent that the nucleus
      has functions extending beyond being a mere genome container. Recent findings
      have revealed that the structural composition of the nucleus changes during
      development and that many of these components exhibit cell- and tissue-specific
      differences. Increasing evidence is pointing to the nucleus being integral to the
      function of the interphase cytoskeleton, with changes to nuclear structural
      proteins having ramifications affecting cytoskeletal organization and the cell's
      interactions with the extracellular environment. Many of these functions
      originate at the nuclear periphery, comprising the nuclear envelope (NE) and
      underlying lamina. Together, they may act as a "hub" in integrating cellular
      functions including chromatin organization, transcriptional regulation,
      mechanosignaling, cytoskeletal organization, and signaling pathways. Interest in
      such an integral role has been largely stimulated by the discovery that many
      diseases and anomalies are caused by defects in proteins of the NE/lamina, the
      nuclear envelopathies, many of which, though rare, are providing insights into
      their more common variants that are some of the major issues of the twenty-first
      century public health. Here, we review the contributions that mouse mutants have
      made to our current understanding of the NE/lamina, their respective roles in
      disease and the use of mice in developing potential therapies for treating the
      diseases. 

PMID- 24947233
TI  - Tri-layered elastomeric scaffolds for engineering heart valve leaflets.
AB  - Tissue engineered heart valves (TEHVs) that can grow and remodel have the
      potential to serve as permanent replacements of the current non-viable prosthetic
      valves particularly for pediatric patients. A major challenge in designing
      functional TEHVs is to mimic both structural and anisotropic mechanical
      characteristics of the native valve leaflets. To establish a more biomimetic
      model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning
      and microfabrication techniques. These constructs were fabricated by assembling
      microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone)
      (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic
      mechanical properties similar to the mechanical characteristics of the native
      heart valves. The engineered scaffolds supported the growth of valvular
      interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D
      structure and promoted the deposition of heart valve extracellular matrix (ECM).
      MSCs were also organized and aligned along the anisotropic axes of the engineered
      tri-layered scaffolds. In addition, the fabricated constructs opened and closed
      properly in an ex vivo model of porcine heart valve leaflet tissue replacement.
      The engineered tri-layered scaffolds have the potential for successful
      translation towards TEHV replacements. 

PMID- 24947236
TI  - Mouse models of lipodystrophy and their significance in understanding fat
      regulation.
AB  - Adipose tissue plays a critical role in human metabolic health. This is most
      dramatically illustrated by the severe metabolic disease that occurs in syndromes
      of lipodystrophy where individuals fail to develop or maintain appropriate
      adipose tissue mass. The most severe form of this disorder is congenital
      generalized lipodystrophy (CGL). Individuals with CGL have a striking paucity of
      adipose tissue and typically display severe metabolic disease with insulin
      resistance and dyslipidemia. Understanding of the metabolic consequences of
      lipodystrophies and their underlying molecular mechanisms will provide new
      information regarding the development and function of human adipose tissue. Mouse
      models of these conditions offer key resources to investigate this in vivo.
      Adipocyte dysfunction is believed to underlie the development of metabolic
      disease in obesity. Hence, understanding how one might beneficially manipulate
      adipose tissue by studying genes whose disruption causes lipodystrophy is likely
      to suggest novel means to improve metabolic health in common obesity. 

PMID- 24947238
TI  - Mouse models of heart failure: cell signaling and cell survival.
AB  - Heart failure is one of the paramount global causes of morbidity and mortality.
      Despite this pandemic need, the available clinical counter-measures have not
      altered substantially in recent decades, most notably in the context of
      pharmacological interventions. Cell death plays a causal role in heart failure,
      and its inhibition poses a promising approach that has not been thoroughly
      explored. In previous approaches to target discovery, clinical failures have
      reflected a deficiency in mechanistic understanding, and in some instances,
      failure to systematically translate laboratory findings toward the clinic. Here,
      we review diverse mouse models of heart failure, with an emphasis on those that
      identify potential targets for pharmacological inhibition of cell death, and on
      how their translation into effective therapies might be improved in the future. 

PMID- 24947239
TI  - Mouse models and aging: longevity and progeria.
AB  - Aging is a complex, multifactorial process that is likely influenced by the
      activities of a range of biological pathways. Genetic approaches to identify
      genes modulating longevity have been highly successful and recent efforts have
      extended these studies to mammalian aging. A variety of genetic models have been
      reported to have enhanced lifespan and, similarly, many genetic interventions
      lead to progeroid phenotypes. Here, we detail and evaluate both sets of models,
      focusing on the insights they provide about the molecular processes modulating
      aging and the extent to which mutations conferring progeroid pathologies really
      phenocopy accelerated aging. 

PMID- 24947240
TI  - LINC complex proteins in development and disease.
AB  - The LINC complex spans the nuclear envelope and plays critical roles in
      coordinating nuclear and cytoplasmic activities and in organizing nuclear and
      cytoskeletal features. LINC complexes are assembled from KASH and SUN-domain
      proteins, which interact in the nuclear envelope and form a physical link between
      the cytoskeleton and the nuclear interior. A number of diseases have been
      associated with mutations in genes coding for LINC complex proteins. Mouse models
      of LINC complex protein have provided valuable insight into LINC complex
      functions and into how these proteins contribute to the various diseases with
      which they have been associated. 

PMID- 24947241
TI  - Mouse models of the nuclear envelopathies and related diseases. Preface.

PMID- 24947242
TI  - IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle
      regulators via DNMT1 upregulation.
AB  - Tumors are influenced by a microenvironment rich in inflammatory cytokines,
      growth factors and chemokines, which may promote tumor growth. Interleukin-6 (IL
      6) is a multifunctional cytokine and known as a regulator of immune and
      inflammation responses. IL-6 has also been reported to be associated with tumor
      progression and chemoresistance in different types of cancers. In our study, we
      demonstrated that IL-6 enriches the properties of lung cancer stem-like cells in
      A549 lung cancer cells cultured in spheroid medium. IL-6 also promotes sphere
      formation and stem-like properties of A549 cells by enhancing cell proliferation.
      Methylation-specific polymerase chain reaction (PCR) was performed and revealed
      that IL-6 increased methylation of p53 and p21 in A549 cancer cells. Western blot
      analysis and quantitative real-time PCR demonstrated that IL-6 increased the
      expression of DNA methyltransferase 1 (DNMT1) in A549 cells cultured in spheroid
      medium, but not the expression of DNMT3a or DNMT3b. Knockdown of DNMT1 eliminated
      IL-6-mediated hypermethylation of cell cycle regulators and enrichment of lung
      cancer stem-like properties. In conclusion, our study, for the first time, shows
      that the IL-6/JAK2/STAT3 pathway upregulates DNMT1 and enhances cancer initiation
      and lung cancer stem cell (CSC) proliferation by downregulation of p53 and p21
      resulting from DNA hypermethylation. Upon blockage of the IL-6/JAK2/STAT3 pathway
      and inhibition of DNMT1, the proliferation of lung CSCs was reduced and their
      formation of spheres and ability to initiate tumor growth were decreased. These
      data suggest that targeting of the IL-6/JAK2/STAT3 signaling pathway and DNMT1
      may become important strategies for treating lung cancer. 

PMID- 24947243
TI  - Building reproductive health research and audit capacity and activity in the
      Pacific Islands (BRRACAP) study: methods, rationale and baseline results.
AB  - BACKGROUND: Clinical research and audit in reproductive health is essential to
      improve reproductive health outcomes and to address the Millennium Development
      Goals 4 and 5. Research training, mentoring and a supportive participatory
      research environment have been shown to increase research activity and capacity
      in low to middle income countries (LMIC). This paper details the methods,
      rationale and baseline findings of a research program aimed at increasing
      clinical research activity and audit in the six Pacific Islands of Fiji, Samoa,
      Tonga, Vanuatu, Cook Islands and the Solomon Islands. METHOD: Twenty-eight
      clinician participants were selected by the five Ministries of Health and the
      Fiji National University to undergo a research capacity building program which
      includes a research workshop and mentoring support to perform research and audit
      as teams in their country. Data on the participants' characteristics, knowledge
      and experiences were collected from structured interviews, questionnaires, focus
      groups, and an online survey. The interviews and the two focus groups were audio
      recorded and all replies were analysed in a thematic framework. RESULTS: The 28
      participants included 9 nurses/midwives, 17 medical doctors of whom 8 were
      specialists in reproductive health and 2 other health workers. Most (24, 86%)
      were required to perform research as part of their employment and yet 17 (61%)
      were not confident in writing a research proposal, 13 (46%) could not use an
      electronic spreadsheet and the same number had not analysed quantitative data.
      The limited environmental enablers contributed to poor capacity with only 11
      (46%) having access to a library, 10 (42%) receiving management support and 6
      (25%) having access to an experienced researcher. Barriers to research that
      affected more than 70% of the participants were time constraints, poor
      coordination, no funding and a lack of skills. CONCLUSION: Building a research
      capacity program appropriate for the diversity of Pacific clinicians required
      research evidence and collaborative effort of key stakeholders in the Pacific
      Islands and the region. The participants had limited research knowledge, skills
      and experience and would require individualized training and continuous intensive
      mentorship to realize their potential as clinician researchers for their services
      in the Pacific.

PMID- 24947244
TI  - Estimation of the genome sizes of the chigger mites Leptotrombidium pallidum and
      Leptotrombidium scutellare based on quantitative PCR and k-mer analysis.
AB  - BACKGROUND: Leptotrombidium pallidum and Leptotrombidium scutellare are the major
      vector mites for Orientia tsutsugamushi, the causative agent of scrub typhus.
      Before these organisms can be subjected to whole-genome sequencing, it is
      necessary to estimate their genome sizes to obtain basic information for
      establishing the strategies that should be used for genome sequencing and
      assembly. METHOD: The genome sizes of L. pallidum and L. scutellare were
      estimated by a method based on quantitative real-time PCR. In addition, a k-mer
      analysis of the whole-genome sequences obtained through Illumina sequencing was
      conducted to verify the mutual compatibility and reliability of the results.
      RESULTS: The genome sizes estimated using qPCR were 191 +/- 7 Mb for L. pallidum
      and 262 +/- 13 Mb for L. scutellare. The k-mer analysis-based genome lengths were
      estimated to be 175 Mb for L. pallidum and 286 Mb for L. scutellare. The
      estimates from these two independent methods were mutually complementary and
      within a similar range to those of other Acariform mites. CONCLUSIONS: The
      estimation method based on qPCR appears to be a useful alternative when the
      standard methods, such as flow cytometry, are impractical. The relatively small
      estimated genome sizes should facilitate whole-genome analysis, which could
      contribute to our understanding of Arachnida genome evolution and provide key
      information for scrub typhus prevention and mite vector competence.

PMID- 24947245
TI  - Conversion of a percutaneous cholecystotomy tube into an internal
      cholecystogastrostomy by use of a novel anastomotic stent.

PMID- 24947247
TI  - Hip rotator strength in healthy young adults measured in hip flexion and
      extension by using a hand-held dynamometer.
AB  - OBJECTIVE: To investigate the effect of hip joint position on hip rotator muscle
      strength of healthy young adults by using a hand-held dynamometer. DESIGN: A
      cross-sectional cohort study. SETTING: A university medical center. PARTICIPANTS:
      Thirty-four healthy (19 women, 15 men; mean [standard deviation] age, 25 +/- 2.3
      years) participated in this study. METHODS: A hand-held dynamometer was used to
      measure the strength of hip internal rotators and external rotators in 2
      positions: hip flexion in sitting and hip extension in supine. The hip was tested
      in a neutral position with respect to rotation, abduction, and adduction.
      Isometric force in pounds was measured as the subject pushed against the device.
      MAIN OUTCOME MEASUREMENTS: For each subject, hip rotator muscle strength
      measurements were taken during a single session. Hypotheses were developed before
      data collection. RESULTS: Hip internal rotators were significantly stronger in
      hip flexion compared with hip extension (P < .01). There was no significant
      difference found in the hip external rotators between the 2 positions.
      CONCLUSIONS: Hip internal rotators and external rotators behave differently when
      comparing strength measurements between the positions of hip flexion and hip
      extension. A hand-held dynamometer provided an objective measurement of strength
      that was clinically feasible to use. Both muscle length and moment arms influence
      force production of the hip rotators as the hip position changes. Understanding
      these relationships may help clinicians interpret strength findings and direct
      intervention toward strengthening the appropriate muscles by using the most
      advantageous position.

PMID- 24947248
TI  - Redundant constraints on human face perception?

PMID- 24947249
TI  - Testosterone serum levels and prostate cancer prognosis: the double face of
      Janus.

PMID- 24947237
TI  - Mouse models of neurodevelopmental disease of the basal ganglia and associated
      circuits.
AB  - This chapter focuses on neurodevelopmental diseases that are tightly linked to
      abnormal function of the striatum and connected structures. We begin with an
      overview of three representative diseases in which striatal dysfunction plays a
      key role--Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome,
      and primary dystonia. These diseases highlight distinct etiologies that disrupt
      striatal integrity and function during development, and showcase the varied
      clinical manifestations of striatal dysfunction. We then review striatal
      organization and function, including evidence for striatal roles in online motor
      control/action selection, reinforcement learning, habit formation, and action
      sequencing. A key barrier to progress has been the relative lack of animal models
      of these diseases, though recently there has been considerable progress. We
      review these efforts, including their relative merits providing insight into
      disease pathogenesis, disease symptomatology, and basal ganglia function.

PMID- 24947251
TI  - Sentinel lymph node biopsy in melanoma: final results of MSLT-I.
AB  - In 1994 an international randomized controlled clinical trial, MSLT-I, opened to
      study the utility of sentinel lymph node biopsy (SLNB) for patients with
      clinically localized melanoma. This trial compared outcomes of patients treated
      with wide local excision (WLE) and SLNB (followed by immediate completion lymph
      node dissection [CLND] for those with a positive sentinel node [SN]) with
      outcomes of patients treated with WLE alone and CLND upon the development of
      clinically apparent disease. In February 2014 the final analysis of long-term
      outcomes data was published. Importantly, these data showed that the rates of
      nodal positivity were the same between the two arms of the trial. Although no
      difference in 10-year melanoma-specific survival was noted between the two arms,
      this was not entirely surprising as the overall rate of nodal disease within the
      trial was 20.8%, meaning that 79.2% of patients could not derive a benefit from
      SLNB. Subset analysis was performed to determine the impact of early intervention
      for those patients most likely to have a benefit from early detection. This
      analysis showed that for patients with nodal disease and intermediate-thickness
      melanoma (defined as 1.2-3.5-mm Breslow depth), early treatment following
      positive SLNB was associated with improved 10-year distant disease-free survival
      and improved 10-year melanoma-specific survival.

PMID- 24947252
TI  - Translational challenges from the 2014 Gastrointestinal Cancers Symposium: toward
      a true tailored therapy through effective research.
AB  - Gastrointestinal Cancers Symposium 2014, San Francisco, CA, USA, 16-18 January
      2014. The Gastrointestinal Cancers Symposium represents an indisputable occasion
      for sharing results and research opportunities for investigators around the
      globe. Across the years along with clinical trials presentations the meeting
      increasingly acquired a distinct role as a scientific arena for translational
      research. Also, this year the need for predictive markers for first-generation
      targeted agents and research about novel biologically driven therapeutic options
      characterized most of the studies presented. We focus here on reports from the
      2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers
      Symposium indicating an opportunity for biological selection of either the
      pharmacological target or the patient population in order to enhance clinical
      outcome.

PMID- 24947253
TI  - EASL HCC summit: liver cancer management.
AB  - EASL HCC Summit, Geneva, Switzerland, 13-16 February 2014. The European
      Association for the Study of the Liver (EASL) organized the 2014 EASL HCC Summit
      in Geneva, Switzerland. We discuss here the most interesting and provocative
      contents from the clinical program of the summit. The objective of this segment
      was to provide an in-depth review on the different management issues related to
      early detection, diagnosis and treatment of hepatocellular carcinoma, and, in
      addition, to highlight the ways of dealing with such an important and rapidly
      involving field.

PMID- 24947254
TI  - Improving the quality of cancer care in America.
AB  - Thomas Feeley is the Helen Shafer Fly Distinguished Professor of Anesthesiology,
      and the Head of the Institute for Cancer Care Innovation at the University of
      Texas MD Anderson Cancer Center (TX, USA), which he has led since its formation
      in 2008. He received his undergraduate degree and M.D. from Boston University
      (MA, USA) and trained in anesthesiology and critical care medicine at Harvard's
      Beth Israel Hospital in Boston. He was a faculty member at Stanford University
      (CA, USA) for 19 years prior to moving to The University of Texas MD Anderson
      Cancer Center in 1997 to lead the then newly created Division of Anesthesiology
      and Critical Care. Dr Feeley served on the Institute of Medicine's Committee on
      Improving the Quality of Cancer Care: Addressing the Challenges of an Aging
      Population that published its report in September of 2013. He was recently
      appointed by Texas Governor Rick Perry to the board of directors of the Texas
      Institute for Health Care Quality and Efficiency. In addition to his research and
      administrative roles, Dr Feeley provides patient care services in the delivery of
      anesthesia.

PMID- 24947255
TI  - Can bevacizumab prolong survival for glioblastoma patients through multiple lines
      of therapy?
AB  - Glioblastoma has a poor prognosis accompanied by debilitating neurological
      symptoms and impaired quality of life. Effective treatment strategies are needed,
      beyond the current standard of care (SOC), to improve outcomes. Glioblastomas are
      highly vascularized with elevated levels of VEGF, representing an appropriate
      target for selective therapies. The role of the anti-VEGF agent bevacizumab in
      newly diagnosed and recurrent glioblastoma is not fully clear at this time.
      Although bevacizumab has demonstrated improvements in progression-free survival
      in newly diagnosed and recurrent glioblastoma, there remain challenges in
      assessing disease progression after antiangiogenic treatment. The bevacizumab
      mechanism of action suggests a rationale for continuing bevacizumab treatment
      through multiple lines of therapy, strengthened by longer progression-free and
      overall survival observed with bevacizumab continuation beyond progression in a
      Phase III study in metastatic colorectal cancer and in pooled analyses of Phase
      II trials in glioblastoma. A novel study (randomized, double-blind, Phase IIIb;
      TAMIGA [MO28347]) aims to evaluate whether continuing bevacizumab plus lomustine
      (as second-line therapy) and SOC (third line and beyond) improves survival
      compared with placebo plus lomustine and then placebo plus SOC in patients with
      glioblastoma who progressed after first-line bevacizumab plus SOC. 

PMID- 24947256
TI  - Ofatumumab as front-line therapy in untreated chronic lymphocytic leukemia.
AB  - Ofatumumab is a fully human IgG1 type I anti-CD20 monoclonal antibody that binds
      to both the small and large loop of the membrane antigen CD20. Much of its
      therapeutic efficacy is derived through complement-dependent cytotoxicity,
      although it also appears to operate via induction of caspase-dependent apoptosis
      and shows potent antibody-dependent cellular phagocytosis. CD20 is an important
      but sometimes difficult antigen to effectively target in chronic lymphocytic
      leukemia (CLL) secondary to its overall dim expression in CLL cells. Currently,
      ofatumumab is approved in the USA and EU for fludarabine- and alemtuzumab
      refractory CLL patients. However, the experience with ofatumumab in untreated CLL
      patients is mounting and shows competitive response and survival rates with an
      acceptable adverse event profile. Herein, we outline the efficacy and toxicities
      of ofatumumab alone and in combination for the front-line treatment of CLL. 

PMID- 24947257
TI  - Volasertib for the treatment of acute myeloid leukemia: a review of preclinical
      and clinical development.
AB  - Volasertib is a potent inhibitor of Polo-like kinase (PLK) 1 and to lesser extent
      also PLK2 and PLK3. PLKs are key regulators of the cell cycle and volasertib
      blocks cells in G2-M phase of the cell cycle. The compound has been evaluated in
      Phase I and II studies in acute myeloid leukemia and solid tumors. Side effects
      are mainly hematological. In acute myeloid leukemia (AML), a randomized Phase II
      study has been conducted in elderly patients unfit for intensive chemotherapy.
      Patients have been randomized to a combination of volarsetib and low-dose
      cytarabine versus low-dose cytarabine alone. Preliminary results show
      significantly higher rates of complete remission and of complete remission with
      incomplete hematological recovery in the combination versus the monotherapy arm,
      with 31% and 13%, respectively. Longer event-free survival was observed with the
      combination with 5.6 versus 2.3 months, respectively (p = 0.0237). These
      encouraging data supported the initiation of an international Phase III trial,
      which currently underway, to confirm these results. Volasertib has not yet been
      approved for regular clinical use. 

PMID- 24947258
TI  - Targeting multiple angiogenic pathways simultaneously: experience with nintedanib
      in non-small-cell lung cancer.
AB  - Angiogenesis plays a major role in the growth and progression of non-small-cell
      lung cancer (NSCLC), and there is increasing interest in the development of
      therapies that block this particular aspect of tumorigenesis. Bevacizumab was the
      first US FDA-approved inhibitor of angiogenesis after demonstrating improved
      progression-free survival and overall survival in combination with chemotherapy
      in treating NSCLC. However, the benefit of bevacizumab is only modest and
      transient as the tumors inevitably develop resistance to this particular
      treatment. Therefore, new therapies are being developed that attempt to inhibit
      angiogenesis through several different pathways. One promising new drug,
      nintedanib, is an oral triple angiokinase inhibitor that acts by blocking not
      only VEGFR, but also FGFR and PDGFR, which are involved in the development of
      resistance to bevacizumab. This article discusses the rationale for this approach
      and summarizes the clinical trial data on nintedanib, including the two most
      recent Phase III trials. 

PMID- 24947260
TI  - Circulating levels of GDF15, MMP7 and miR-200c as a poor prognostic signature in
      gastric cancer.
AB  - AIM: To analyze GDF15 and MMP7 serum levels as diagnostic biomarkers in gastric
      cancer (GC) patients. The prognostic value of GDF15 and MMP7 serum levels in
      combination with miR-200c blood expression was also analyzed. PATIENTS & METHODS:
      Fifty-two GC and 23 control samples were included. RESULTS: GDF15 and MMP7 proved
      to be powerful tools for GC diagnosis. Increased levels of GDF15 and MMP7 were
      associated with shorter progression-free survival and overall survival in
      univariate analysis. In multivariate analysis, the combination of high levels of
      GDF15, MMP7 and miR-200c was an independent predictor for death (p = 0.033).
      CONCLUSION: GDF15 and MMP7 serum levels have diagnostic value for GC. The
      combination marker formed by GDF15, MMP7 and miR-200c is indicative of adverse
      evolution in GC patients.

PMID- 24947261
TI  - Protective effect of Panax ginseng in cisplatin-induced cachexia in rats.
AB  - AIM: This study investigated the protective effect of a standardized extract of
      Panax ginseng on multiple cisplatin-induced 'sickness behaviors' (model of cancer
      induced cachexia) in rats. MATERIALS & METHODS: Cisplatin was administered twice
      weekly (1-2 mg/kg, intraperitoneal) for 5 consecutive weeks. Panax ginseng
      extract (0, 25 and 50 mg/kg, intragastric) was administered daily over the 5-week
      period of cisplatin exposure. Malaise, bodyweight and temperature, pain
      sensitivity, and endurance running were recorded at baseline and at 5 weekly
      intervals. RESULTS: Treatment with cisplatin produced severe signs of malaise,
      marked loss of bodyweight, hypothermia, hyperalgesia and reduction in running
      time. Treatment with Panax ginseng extract completely prevented all cisplatin
      induced alterations. CONCLUSION: These data indicate that treatment with Panax
      ginseng extract exerted a protective effect in a rat model of cachexia and
      suggest that Panax ginseng extract may be a therapeutic promising tool for
      supportive care in oncology.

PMID- 24947263
TI  - Low-fidelity compensatory backup alternative DNA repair pathways may unify
      current carcinogenesis theories.
AB  - The somatic mutation carcinogenesis theory has dominated for decades. The
      alternative theory, tissue organization field theory, argues that the development
      of cancer is determined by the surrounding microenvironment. However, neither
      theory can explain all features of cancer. As cancers share the features of
      uncontrolled proliferation and genomic instability, they are likely to have the
      same pathogenesis. It has been found that various DNA repair pathways within a
      cell crosstalk with one another, forming a DNA repair network. When one DNA
      repair pathways is defective, the others may work as compensatory backups. The
      latter pathways are explored for synthetic lethal anticancer therapy. In this
      article, we extend the concept of compensatory alternative DNA repair to unify
      the theories. We propose that the microenvironmental stress can activate low
      fidelity compensatory alternative DNA repair, causing mutations. If the mutation
      occurs to a DNA repair gene, this secondarily mutated gene can lead to even more
      mutated genes, including those related to other DNA repair pathways, eventually
      destabilizing the genome. Therefore, the low-fidelity compensatory alternative
      DNA repair may mediate microenvironment-dependent carcinogenesis. The proposal
      seems consistent with the view of evolution: the environmental stress causes
      mutations to adapt to the changing environment. 

PMID- 24947259
TI  - Association of CDC25 phosphatase family polymorphisms with the efficacy/toxicity
      of platinum-based chemotherapy in Chinese advanced NSCLC patients.
AB  - AIM: To explore relationships between single nucleotide polymorphisms (SNPs) of
      the CDC25 protein family and the survival and chemotherapy responses of patients
      with advanced non-small-cell lung cancer (NSCLC). METHODS & MATERIALS: We
      genotyped 14 SNPs of the CDC25 family in 663 Chinese patients with advanced NSCLC
      who were treated with first-line platinum-based chemotherapy and, in evaluable
      patients, analyzed relationships between the CDC25 family and the efficacy of
      platinum-based chemotherapy. RESULTS: CDC25A rs3731513 and rs1380053, CDC25C
      rs6861656, CDC25A haplotype T/A/A/A/C and CDC25C haplotype A/G/G/G/C were
      significantly associated with the patients' progression-free survival. In
      addition, CDC25B rs3761218 and haplotype G/T/G/G were associated with the
      occurrence of severe toxicity with platinum-based chemotherapy, especially
      gastrointestinal and hematological toxicity. CONCLUSION: These findings reveal a
      relationship between genetic variations of the CDC25 family and the efficacy and
      toxicity of platinum-based chemotherapy in patients with advanced NSCLC,
      especially in those with non-squamous-cell carcinoma.

PMID- 24947262
TI  - Targeting DNA repair pathways for cancer treatment: what's new?
AB  - Disruptions in DNA repair pathways predispose cells to accumulating DNA damage. A
      growing body of evidence indicates that tumors accumulate progressively more
      mutations in DNA repair proteins as cancers progress. DNA repair mechanisms
      greatly affect the response to cytotoxic treatments, so understanding those
      mechanisms and finding ways to turn dysregulated repair processes against
      themselves to induce tumor death is the goal of all DNA repair inhibition
      efforts. Inhibition may be direct or indirect. This burgeoning field of research
      is replete with promise and challenge, as more intricacies of each repair pathway
      are discovered. In an era of increasing concern about healthcare costs, use of
      DNA repair inhibitors can prove to be highly effective stewardship of R&D
      resources and patient expenses. 

PMID- 24947264
TI  - Immunotherapeutic and oncolytic viral therapeutic strategies in pancreatic
      cancer.
AB  - Pancreatic adenocarcinoma is an aggressive disease with dismal outcomes despite
      recent advances using combination chemotherapeutic regimens. The lack of an
      adequate immune response to malignant cells has been identified as a factor
      associated with tumor aggressiveness and refractoriness to systemic treatment.
      Preclinical and early clinical studies have identified numerous immunotherapeutic
      and oncolytic viral therapeutic strategies aimed towards amplifying the immune
      reaction to pancreatic cancer and have established encouraging results. Promising
      antitumor efficacy has been observed both in vitro and in vivo with many of these
      approaches. These novel applications have also led to improved understanding of
      the process of pancreatic tumor growth and invasion, knowledge of the tumor
      microenvironment and have pioneered further investigations of similar therapies.
      Here we review both immunotherapeutic and oncolytic viral therapeutic strategies
      in pancreatic cancer. 

PMID- 24947266
TI  - Emerging applications of stereotactic body radiotherapy.
AB  - Stereotactic body radiotherapy (SBRT) has been used extensively in patients with
      lung, liver and spinal tumors, and the treatment outcomes are very favorable. For
      certain conditions such as medically inoperable stage I non-small-cell lung
      cancer, liver and lung oligometastases, primary liver cancer and spinal
      metastases, SBRT is regarded as one of the standard therapies. In the recent
      years, the use of SBRT has been extended to other disease conditions and sites
      such as recurrent head and neck cancer, renal cell carcinoma, prostate cancer,
      adrenal metastasis, pancreatic cancer, gynecological malignancies, spinal cord
      compression, breast cancer, and stage II-III non-small-cell lung cancer.
      Preliminary data in the literature show promising results but the follow-up
      intervals are short for most studies. This paper will provide an overview of
      these emerging applications. 

PMID- 24947267
TI  - 3D tumor models: history, advances and future perspectives.
AB  - Evaluation of cancer therapeutics by utilizing 3D tumor models, before clinical
      studies, could be more advantageous than conventional 2D tumor models (monolayer
      cultures). The 3D systems mimic the tumor microenvironment more closely than 2D
      systems. The following review discusses the various 3D tumor models present today
      with the advantages and limitations of each. 3D tumor models replicate the
      elements of a tumor microenvironment such as hypoxia, necrosis, angiogenesis and
      cell adhesion. The review introduces application of techniques such as
      microfluidics, imaging and tissue engineering to improve the 3D tumor models.
      Despite their tremendous potential to better screen chemotherapeutics, 3D tumor
      models still have a long way to go before they are used commonly as in vitro
      tumor models in pharmaceutical industrial research. 

PMID- 24947265
TI  - Postradiation imaging changes in the CNS: how can we differentiate between
      treatment effect and disease progression?
AB  - A familiar challenge for neuroradiologists and neuro-oncologists is
      differentiating between radiation treatment effect and disease progression in the
      CNS. Both entities are characterized by an increase in contrast enhancement on
      MRI and present with similar clinical signs and symptoms that may occur either in
      close temporal proximity to the treatment or later in the disease course. When
      radiation-related imaging changes or clinical deterioration are mistaken for
      disease progression, patients may be subject to unnecessary surgery and/or a
      change from otherwise effective therapy. Similarly, when disease progression is
      mistaken for treatment effect, a potentially ineffective therapy may be continued
      in the face of progressive disease. Here we describe the three types of radiation
      injury to the brain based on the time to development of signs and symptoms-
      acute, subacute and late--and then review specific imaging changes after
      intensity-modulated radiation therapy, stereotactic radiosurgery and
      brachytherapy. We provide an overview of these phenomena in the treatment of a
      wide range of malignant and benign CNS illnesses. Finally, we review the
      published data regarding imaging techniques under investigation to address this
      well-known problem.

PMID- 24947269
TI  - Mutations in Soviet public health science: post-Lysenko medical genetics, 1969
      1991.
AB  - This paper traces the integration of human genetics with Soviet public health
      science after the Lysenko era. For nearly three decades, USSR biology pursued its
      own version of anti-bourgeois, Soviet 'creative Darwinism', departing from
      western, post-WWII scientific developments. After Lysenko was suspended, research
      niches of immunology, biophysics and mutation research formed the basis of new
      departments at the Institute of Medical Genetics, which was founded in 1969 as
      part of the Soviet Academy of Medical Sciences. Focussing on early research
      activities and collaborations at the institute, I show how the concept of
      mutagenesis, a pivotal issue during the Cold War, became mobilized from
      Drosophila genetics to human heredity and to society as a whole. This mode of
      scaling up and down through population studies shaped not only Soviet human
      biology and genetics; it also brought about changes in clinical practice and
      public health as well as in the monitoring and regulation of mutagenic agents in
      the environment. 

PMID- 24947270
TI  - Cell pairing using microwell array electrodes based on dielectrophoresis.
AB  - We report a simple device with an array of 10,000 (100 * 100) microwells for
      producing vertical pairs of cells in individual microwells with a rapid
      manipulation based on positive dielectrophoresis (p-DEP). The areas encircled
      with micropoles which fabricated from an electrical insulating photosensitive
      polymer were used as microwells. The width (14 MUm) and depth (25 MUm) of the
      individual microwells restricted the size to two vertically aligned cells. The
      DEP device for the manipulation of cells consisted of a microfluidic channel with
      an upper indium tin oxide (ITO) electrode and a lower microwell array electrode
      fabricated on an ITO substrate. Mouse myeloma cells stained in green were trapped
      within 1 s in the microwells by p-DEP by applying an alternating current voltage
      between the upper ITO and the lower microwell array electrode. The cells were
      retained inside the wells even after switching off the voltage and washing with a
      fluidic flow. Other myeloma cells stained in blue were then trapped in the
      microwells occupied by the cells stained in green to form the vertical cell
      pairing in the microwells. Cells stained in different colors were paired within
      only 1 min and a pairing efficiency of over 50% was achieved.

PMID- 24947271
TI  - Systematic review and meta-analysis of behavioral interventions for pediatric
      insomnia.
AB  - OBJECTIVE: To evaluate and quantify the evidence for behavioral interventions for
      pediatric insomnia. METHODS: Meta-analysis of 16 controlled trials and
      qualitative analysis of 12 within-subject studies were conducted (total n =
      2,560). RESULTS: Meta-analysis found significant effects for four specified sleep
      outcomes: sleep-onset latency, number of night wakings, and duration of night
      wakings, and sleep efficiency, with small to large effect sizes across the
      controlled clinical trials involving typical children. No significant effects
      were found for the two studies conducted with special needs populations. Finally,
      within-subjects studies demonstrated significant effects for all sleep outcomes
      with large effect sizes. Risk of bias assessment and GRADE ratings of the quality
      of the evidence are described. CONCLUSION: Moderate-level evidence supports
      behavioral interventions for pediatric insomnia in young children. However, low
      evidence for children, adolescents, and those with special needs (due to a lack
      of studies that met inclusion criteria) highlights the need for future research.

PMID- 24947268
TI  - A systematic review of outcome measurements and quality of studies evaluating
      fixed tooth-supported restorations.
AB  - PURPOSE: The purpose of this systematic review was to review clinical studies of
      fixed tooth-supported prostheses, and to assess the quality of evidence with an
      emphasis on the assessment of the reporting of outcome measurements. Multiple
      hypotheses were generated to compare the effect of study type on different
      outcome modifiers and to compare the quality of publications before and after
      January 2005. MATERIALS AND METHODS: An electronic search was conducted using
      specific databases (MEDLINE via Ovid, EMBASE via Ovid, Cochrane Library) through
      July 2012. This was complemented by hand searching the past 10 years of issues of
      the Journal of Oral Rehabilitation, Journal of Prosthetic Dentistry, Journal of
      Prosthodontics, and the International Journal of Prosthodontics. All experimental
      and observational clinical studies evaluating survival, success, failure, and
      complications of tooth-supported extracoronal fixed partial dentures, crowns, and
      onlays were included. No restrictions on age or follow-up time were placed.
      RESULTS: The electronic search generated 14,869 papers, of which 206 papers were
      included for full-text review. Hand-searching added 23 papers. Inclusion criteria
      were met by 182 papers and were included for the review. The majority were
      retrospective studies. Only 8 (4.4%) were randomized controlled trials. The
      majority of the studies measured survival and failure, and few studies recorded
      data on success; however, more than 60% of the studies failed to define survival,
      success, and failure. Many studies did not use any standardized criteria for
      assessment of the quality of the restorations and, when standardized criteria
      were used, they were modified, thereby not allowing for comparisons with other
      studies. There was an increase of 21.8% in the number of studies evaluating
      outcome measurements of all-ceramic restorations in past 8 years. CONCLUSIONS:
      Prosthodontic literature presents with a reduced percentage of RCTs compared to
      other disciplines in dentistry. The overall quality of recording prosthodontic
      outcome measurements has not improved greatly in the past 8 years.

PMID- 24947273
TI  - Anti-inflammatory activity and molecular mechanism of Oolong tea theasinensin.
AB  - Oolong tea theasinensins are a group of tea polyphenols different from green tea
      catechins and black tea theaflavins, and they are considered as bioactive
      compounds in Oolong tea. In the present study, based on the properties of
      theasinensin and information about inflammatory processes, we investigated the
      anti-inflammatory activity and molecular mechanisms of theasinensin A (TSA) in
      both cell and animal models. In the cell model, TSA reduced the levels of pro
      inflammatory mediators including inducible nitric oxide synthase (iNOS), nitric
      oxide (NO), interleukin-12 (IL-12) (p70), tumor necrosis factor alpha (TNF
      alpha), and monocyte chemotactic protein-1 (MCP-1) induced by lipopolysaccharide
      (LPS). Cellular signaling analysis revealed that TSA downregulated MAPK/ERK
      kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling. Pull-down
      assay and affinity data revealed that TSA might directly bind to MEK-ERK for the
      inhibitory action. In the animal model, TSA suppressed the production of IL-12
      (p70), TNF-alpha, and MCP-1 and attenuated mouse paw edema induced by LPS. 

PMID- 24947272
TI  - A pilot study of the association between sleep disturbance in children with liver
      transplants and parent and family health-related quality of life.
AB  - OBJECTIVE: To investigate the relationship between sleep disturbance in children
      with liver transplants and parent and family health-related quality of life
      (HRQOL). METHOD: 47 parents of children with liver transplants completed measures
      of child sleep and family HRQOL. Relationships between sleep and HRQOL and
      differences in HRQOL between groups with scores above and below the cutoff on a
      pediatric sleep measure were examined. RESULTS: Parents endorsed higher rates of
      sleep-related breathing disorder (SRBD) and restless legs syndrome and periodic
      limb movements during sleep (RLS/PLMS) and lower HRQOL compared with published
      data. Significant correlations were found between SRBD and RLS/PLMS and HRQOL,
      and significant group differences in HRQOL were found between groups above and
      below the cutoff for behavior problems and RLS/PLMS. CONCLUSION: There are
      significant relationships between symptoms of SRBD and RLS/PLMS in children with
      liver transplants and family HRQOL. Behavior problems may account for these
      strong relationships.

PMID- 24947274
TI  - Diet and growth in infancy: relationship to socioeconomic background and to
      health and development in the Avon Longitudinal Study of Parents and Children.
AB  - To assess the relationship between diet and growth in infancy and socioeconomic
      background, all publications from the Avon Longitudinal Study of Parents and
      Children (ALSPAC) covering breastfeeding, diet and growth in infancy, and the
      associations of these factors with socioeconomic background and later health and
      developmental outcomes were reviewed. Diet was assessed by parent-completed food
      records and parent-completed food frequency questionnaires covering infant
      feeding practices. Infancy growth was monitored through routine screening and by
      standardized measurements. Indicators of socioeconomic background were obtained
      by parent-completed questionnaires. Childhood outcomes were measured by
      standardized procedures. Rapid early weight gain was associated with later
      obesity. Longer breastfeeding duration was associated with lower body fat, but
      not lower body mass index, and with higher IQ in mid-childhood. Breastfed infants
      were better at regulating their energy intake than bottle-fed infants. In bottle
      fed infants, energy intake at 4 months was associated with greater weight gain up
      to 5 years of age. Feeding cow's milk as a main drink in infancy was associated
      with anemia and high salt intake. Maternal education was a strong determinant of
      dietary differences: low education was associated with never breastfeeding and
      not following feeding guidelines. ALSPAC has provided unique insights into the
      relationship between diet and growth in infancy and later developmental outcomes.

PMID- 24947277
TI  - Tuning the energy migration and new insights into the mechanism of upconversion.
AB  - The past decade has seen extensive developments in the field of upconversion
      nanotechnology, which has found applications in various fields. Different
      applications require different emission wavelengths from nanoparticles, and
      significant research has been undertaken to fine tune individual emission peaks
      in shorter wavelengths without much success. Recently, a novel class of
      upconversion nanoparticles with an orthorhombic crystal structure has been
      developed, which enables high concentrations of activator ions to be used without
      concentration quenching and also allows for the excellent tuning of shorter
      emission wavelengths. 

PMID- 24947276
TI  - Metabolite of tryptophan promoting changes in EEG signal and the oxidative status
      of the brain.
AB  - Tryptophan is an essential amino acid precursor of neurotransmitter serotonin and
      triptamine. During its metabolism, indole-3-acetic acid (IAA) is generated; this
      substance presents both antioxidant and prooxidant effects in different
      biological systems in addition to hipoglicemic effects. To date,
      electroencephalography (EEG) has been used to evaluate the temporal effect of
      several substances in neurotransmission. The goal of this study was to
      characterize the effect of IAA in the brain by analysing the EEG signal and
      evaluate the oxidative status by means of biochemical parameters. The EEG was
      acquired by using a noninvasive method, and the brain electric signal was
      analysed by advanced digital signal processing techniques to determinate the
      energy signal filtered in different band frequencies. Furthermore, the oxidative
      status of the brain was investigated by measuring the activity of antioxidant
      enzymes and lipid peroxidation as well as blood glucose rates of the animals
      treated with different doses of IAA. Our results showed the relationship of IAA
      administration with changes in EEG signals. The oxidative status of the brain was
      modified by IAA after 14 days of treatment.

PMID- 24947275
TI  - Role of beta-lactamase residues in a common interface for binding the
      structurally unrelated inhibitory proteins BLIP and BLIP-II.
AB  - The beta-lactamase inhibitory proteins (BLIPs) are a model system for examining
      molecular recognition in protein-protein interactions. BLIP and BLIP-II are
      structurally unrelated proteins that bind and inhibit TEM-1 beta-lactamase. Both
      BLIPs share a common binding interface on TEM-1 and make contacts with many of
      the same TEM-1 surface residues. BLIP-II, however, binds TEM-1 over 150-fold
      tighter than BLIP despite the fact that it has fewer contact residues and a
      smaller binding interface. The role of eleven TEM-1 amino acid residues that
      contact both BLIP and BLIP-II was examined by alanine mutagenesis and
      determination of the association (k on) and dissociation (k off) rate constants
      for binding each partner. The substitutions had little impact on association
      rates and resulted in a wide range of dissociation rates as previously observed
      for substitutions on the BLIP side of the interface. The substitutions also had
      less effect on binding affinity for BLIP than BLIP-II. This is consistent with
      the high affinity and small binding interface of the TEM-1-BLIP-II complex, which
      predicts per residue contributions should be higher for TEM-1 binding to BLIP-II
      versus BLIP. Two TEM-1 residues (E104 and M129) were found to be hotspots for
      binding BLIP while five (L102, Y105, P107, K111, and M129) are hotspots for
      binding BLIP-II with only M129 as a common hotspot for both. Thus, although the
      same TEM-1 surface binds to both BLIP and BLIP-II, the distribution of binding
      energy on the surface is different for the two target proteins, that is,
      different binding strategies are employed.

PMID- 24947278
TI  - Clinical applications of herbal medicines for anxiety and insomnia; targeting
      patients with bipolar disorder.
AB  - OBJECTIVES: Patients with bipolar disorder frequently continue to experience
      residual anxiety and insomnia between mood episodes. In real-world practice,
      patients increasingly self-prescribe alternative medicines. METHODS: We reviewed
      case reports, open-label, and placebo-controlled trials investigating the use of
      herbal medicines to treat anxiety and insomnia, and discussed their potential
      applications for bipolar disorder. RESULTS: Eleven herbal medicines that have
      been studied in human subjects are included in this review. Mechanisms of action,
      efficacy, side effects, and drug-drug interactions are discussed. Based on
      currently available evidence, valerian seems to be the most promising candidate
      for insomnia and anxiety in bipolar disorder. CONCLUSIONS: Adjunctive herbal
      medicines may have the potential to alleviate these symptoms and improve the
      outcomes of standard treatment, despite limited evidence. Physicians need to have
      a more in-depth understanding of the evidence of benefits, risks, and drug
      interactions of alternative treatments.

PMID- 24947279
TI  - Risk assessment and clinical decision-making.

PMID- 24947280
TI  - Violence risk assessment has not been shown to reduce violence.

PMID- 24947282
TI  - Anxious mothers... anxious babies?

PMID- 24947281
TI  - Probiotics in the prevention of eczema: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate a multistrain, high-dose probiotic in the prevention of
      eczema. DESIGN: A randomised, double-blind, placebo-controlled, parallel group
      trial. SETTINGS: Antenatal clinics, research clinic, children at home. PATIENTS:
      Pregnant women and their infants. INTERVENTIONS: Women from 36 weeks gestation
      and their infants to age 6 months received daily either the probiotic
      (Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium
      animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20; total of
      10(10) organisms/day) or matching placebo. MAIN OUTCOME MEASURE: Diagnosed eczema
      at age 2 years. Infants were followed up by questionnaire. Clinical examination
      and skin prick tests to common allergens were done at 6 months and 2 years.
      RESULTS: The cumulative frequency of diagnosed eczema at 2 years was similar in
      the probiotic (73/214, 34.1%) and placebo arms (72/222, 32.4%; OR 1.07, 95% CI
      0.72 to 1.6). Among the secondary outcomes, the cumulative frequency of skin
      prick sensitivity at 2 years was reduced in the probiotic (18/171; 10.5%)
      compared with the placebo arm (32/173; 18.5%; OR 0.52, 95% CI 0.28 to 0.98). The
      statistically significant differences between the arms were mainly in
      sensitisation to cow's milk and hen's egg proteins at 6 months. Atopic eczema
      occurred in 9/171 (5.3%) children in the probiotic arm and 21/173 (12.1%) in the
      placebo arm (OR 0.40, 95% CI 0.18 to 0.91). CONCLUSIONS: The study did not
      provide evidence that the probiotic either prevented eczema during the study or
      reduced its severity. However, the probiotic seemed to prevent atopic
      sensitisation to common food allergens and so reduce the incidence of atopic
      eczema in early childhood. TRIAL REGISTRATION NUMBER: ISRCTN26287422.

PMID- 24947283
TI  - Calcium deficiency rickets: extending the spectrum of 'nutritional' rickets.

PMID- 24947284
TI  - Can silylenes rival transition metal systems in bond-strengthening pi-back
      donation? A computational investigation.
AB  - Full quantum chemical calculations with density functional theory (DFT) show that
      bond-strengthening back-donation to a pi-diborene, recently discovered for
      transition metal systems (Braunschweig and co-workers, Nat. Chem., 2013, 5, 115
      121), would be just as favored for Main Group silylene complexes. This result not
      only shows the range and applicability of the bond-strengthening back-bonding
      interaction, but also showcases the capacity of silylene complexes to do new
      chemistry, such as the cooperative activation of carbon monoxide and carbon
      dioxide. 

PMID- 24947285
TI  - Response to letter regarding article, "Neurological, functional, and cognitive
      stroke outcomes in Mexican Americans".

PMID- 24947286
TI  - Incidence of symptomatic hemorrhage in patients with lobar microbleeds.
AB  - BACKGROUND AND PURPOSE: Lobar microbleeds suggestive of cerebral amyloid
      angiopathy (CAA) are often identified on MRI in the absence of lobar
      intracerebral hemorrhage (ICH). We compared the baseline characteristics and risk
      of subsequent ICH among such patients to those presenting with CAA-related lobar
      ICH. METHODS: Clinical data (demographics, risk factors), apolipoprotein E
      genotype, neuroimaging markers of CAA severity (microbleed counts, leukoaraiosis
      volume), and clinical outcomes (incidence rates of ICH and death during a mean
      follow-up of 5.3+/-3.8 years) were compared between 63 patients enrolled because
      of incidentally found microbleeds and 316 with CAA-related ICH, in our
      prospectively enrolled cohort. Predictors of incident ICH were explored in the
      microbleed-only patients using multivariable Cox regression models. RESULTS:
      Microbleed-only patients shared similar demographic, apolipoprotein E, and
      vascular risk profiles with lobar ICH patients, but had more lobar microbleeds
      (median, 10 versus 2; P<0.001) and higher leukoaraiosis volumes (median, 31
      versus 23 mL; P=0.02). Microbleed-only patients had a nontrivial incidence rate
      of ICH, not different from patients presenting with ICH (5 versus 8.9 per 100
      person-years; adjusted hazard ratio, 0.58; 95% confidence interval, 0.31-1.06;
      P=0.08). Microbleed-only patients had a higher mortality rate (hazard ratio,
      1.67; 95% confidence interval, 1.1-2.6) compared with ICH survivors. Warfarin use
      and increasing age were independent predictors of future ICH among microbleed
      only patients after correction for other covariates. CONCLUSIONS: Patients
      presenting with isolated lobar microbleeds on MRI have a genetic, neuroimaging,
      and hemorrhagic risk profile suggestive of severe CAA pathology. They have a
      substantial risk of incident ICH, potentially affecting decisions regarding
      anticoagulation in clinical situations.

PMID- 24947288
TI  - Common caregiver issues and nursing interventions after a stroke.

PMID- 24947287
TI  - Cerebrovascular events in 21 105 patients with atrial fibrillation randomized to
      edoxaban versus warfarin: Effective Anticoagulation with Factor Xa Next
      Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48.
AB  - BACKGROUND AND PURPOSE: The once-daily oral factor Xa inhibitor, edoxaban, is as
      effective as warfarin in preventing stroke and systemic embolism while decreasing
      bleeding in a phase III trial of patients with atrial fibrillation at moderate
      high stroke risk. Limited data regarding cerebrovascular events with edoxaban
      were reported previously. METHODS: We analyzed the subtypes of cerebrovascular
      events in 21 105 patients participating in Effective Anticoagulation with Factor
      Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction
      48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin
      versus 2 edoxaban regimens (high dose, low dose). The primary end point for this
      prespecified analysis of cerebrovascular events was all stroke (ischemic plus
      hemorrhagic), defined as an abrupt onset of focal neurological deficit because of
      infarction or bleeding with symptoms lasting >=24 hours or fatal in <24 hours.
      Independent stroke neurologists unaware of treatment adjudicated all
      cerebrovascular events. RESULTS: Patients randomized to high-dose edoxaban had
      fewer strokes on-treatment (hazard ratio, 0.80; 95% confidence interval, 0.65
      0.98) than warfarin (median time-in-therapeutic range, 68.4%); patients in the
      low-dose edoxaban group had similar rates (hazard ratio, 1.10 versus warfarin;
      95% confidence interval, 0.91-1.32). Rates of ischemic stroke or transient
      ischemic attack were similar with high-dose edoxaban (1.76% per year) and
      warfarin (1.73% per year; P=0.81), but more frequent with low-dose edoxaban
      (2.48% per year; P<0.001). Both edoxaban regimens significantly reduced
      hemorrhagic stroke and other subtypes of intracranial bleeds. CONCLUSIONS: In
      patients with atrial fibrillation, once-daily edoxaban was as effective as
      warfarin in preventing all strokes, with significant reductions in various
      subtypes of intracranial bleeding. Ischemic cerebrovascular event rates were
      similar with high-dose edoxaban and warfarin, whereas low-dose edoxaban was less
      effective than warfarin. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00781391.

PMID- 24947289
TI  - Letter by Wehrum and Harloff regarding article, "Complex atheromatous plaques in
      the descending aorta and the risk of stroke: a systematic review and meta
      analysis".

PMID- 24947290
TI  - Predictors of early mortality in young adults after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Patient and radiological characteristics of intracerebral
      hemorrhage (ICH), surgical treatment, and outcome after ICH are interrelated. Our
      purpose was to define whether these characteristics or surgical treatment
      correlate with mortality among young adults. METHODS: We retrospectively reviewed
      clinical and imaging data of all first-ever nontraumatic patients with ICH
      between 16 and 49 years of age treated in our hospital between January 2000 and
      March 2010 and linked these data with national causes of death registry. A
      logistic regression analysis of factors associated with 3-month mortality and a
      propensity score comparison between patients treated conservatively and
      operatively was performed. RESULTS: Among the 325 eligible patients (59.4% men),
      factors associated with 3-month mortality included higher National Institutes of
      Health Stroke Scale score, infratentorial location, hydrocephalus, herniation,
      and multiple hemorrhages. Adjusted for these factors, as well as demographics,
      ICH volume, and the underlying cause, surgical evacuation was associated with
      lower 3-month mortality (odds ratio, 0.06; 95% confidence interval, 0.02-0.21).
      In propensity score-matched analysis, 3-month case fatality rates were 3-fold in
      those treated conservatively (27.5% versus 7.8%; P<0.001). CONCLUSIONS: The
      predictors of short-term case fatality are alike in young and elderly patients
      with ICH. However, initial hematoma evacuation was associated with lower 3-month
      case fatality in our young patients with ICH.

PMID- 24947292
TI  - Response to letter regarding article, "Complex atheromatous plaques in the
      descending aorta and the risk of stroke: a systematic review and meta-analysis".

PMID- 24947291
TI  - Acute and delayed deferoxamine treatment attenuates long-term sequelae after
      germinal matrix hemorrhage in neonatal rats.
AB  - BACKGROUND AND PURPOSE: This study investigated if acute and delayed deferoxamine
      treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH).
      METHODS: Bacterial collagenase (0.3 U) was infused intraparenchymally into the
      right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals
      received either deferoxamine or vehicle twice a day for 7 consecutive days.
      Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH.
      Long-term neurocognitive deficits and motor coordination were assessed using
      Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH.
      At 28 days post-GMH, brain morphology was assessed and extracellular matrix
      protein (fibronectin and vitronectin) expression was determined. RESULTS: Acute
      and delayed deferoxamine treatment improved long-term motor and cognitive
      function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with
      improved overall brain morphology at 28 days post-GMH, reducing white matter
      loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical
      loss. GMH resulted in significantly increased expression of fibronectin and
      vitronectin, which was reversed by acute and delayed deferoxamine treatment.
      CONCLUSIONS: Acute and delayed deferoxamine administration ameliorated long-term
      sequelae after GMH.

PMID- 24947293
TI  - Persistent racial disparity in stroke hospitalization and economic impact in
      young adults in the buckle of stroke belt.
AB  - BACKGROUND AND PURPOSE: Mounting evidence points to a decline in stroke
      incidence. However, little is known about recent patterns of stroke
      hospitalization within the buckle of the stroke belt. This study aims to
      investigate the age- and race-specific secular trends in stroke hospitalization
      rates, inpatient stroke mortality rates, and related hospitalization charges
      during the past decade in South Carolina. METHODS: Patients from 2001 to 2010
      were identified from the State Inpatient Hospital Discharge Database with a
      primary discharge diagnosis of stroke (International Classification of Diseases,
      Ninth Revision codes: 430-434, 436, 437.1). Age- and race-stroke-specific
      hospitalization rates, hospital charges, charges associated with racial
      disparity, and 30-day stroke mortality rates were compared between blacks and
      whites. RESULTS: Of the 84,179 stroke hospitalizations, 31,137 (37.0%) were from
      patients aged<65 years and 29,846 (35.5%) were blacks. Stroke hospitalization
      rates decreased in the older population (aged>=65 years) for both blacks and
      whites (P<0.001) but increased among the younger group (aged<65 years; P=0.004);
      however, this increase was mainly driven by a 17.3% rise among blacks (P=0.001),
      with no difference seen among whites (P=0.84). Of hospital charges totaling $2.77
      billion, $453.2 million (16.4%) are associated with racial disparity (79.6% from
      patients aged<65 years). Thirty-day stroke mortality rates decreased in all age
      race-stroke-specific groups (P<0.001). CONCLUSIONS: The stroke hospitalization
      rate increased in the young blacks only, which results in a severe and persistent
      racial disparity. It highlights the urgent need for a racial disparity reduction
      in the younger population to alleviate the healthcare burden.

PMID- 24947294
TI  - Letter by Chen et al regarding article, "Neurological, functional, and cognitive
      stroke outcomes in Mexican Americans".

PMID- 24947296
TI  - From the Editor-in-Chief.

PMID- 24947297
TI  - Evidence-based research in nursing administration: the time is now.
AB  - The paper "Working in Canada or the United States: Perceptions of Canadian Nurses
      Living in a Border Community" by Cameron, Armstrong-Stassen, Rajacich and Freeman
      sheds new light on the recruitment and retention factors that influence the
      reasons nurses select certain work environments. In a border city where Canadian
      nurses have a choice between working in the United States or Canada, the
      researchers found that full-time employment was the most important factor
      attracting nurses to specific institutions, followed by educational
      opportunities, relationships with physicians and supervisors, and scheduling that
      is compatible with the nurse's lifestyle. While these employment factors have
      been identified in the past, the research reminds us of the importance of
      focusing on the elements that attract nurses to specific healthcare institutions
      and encourage them to remain, as well as the relative importance of these
      factors. 

PMID- 24947295
TI  - High-resolution magnetic resonance wall imaging findings of Moyamoya disease.
AB  - BACKGROUND AND PURPOSE: Diagnosis of Moyamoya disease (MMD) is based on the
      characteristic angiographic findings. However, differentiating MMD from
      intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall
      imaging findings on high-resolution magnetic resonance imaging between MMD and
      ICAD. METHODS: High-resolution magnetic resonance imaging was performed on 32
      patients with angiographically proven MMD and 16 patients with acute infarcts
      because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle
      cerebral artery were analyzed for wall enhancement and remodeling. RESULTS:
      Enhancement patterns and distribution were different. Most patients with MMD
      (90.6%) showed concentric enhancement on distal internal carotid arteries and
      middle cerebral arteries, whereas focal eccentric enhancement was observed on the
      symptomatic segment in ICAD. MMD was characterized by middle cerebral artery
      shrinkage; the remodeling index and wall area were lower in MMD than in ICAD
      (remodeling index, 0.19+/-0.11 versus 1.00+/-0.43; wall area, 0.32+/-0.22 versus
      6.00+/-2.72; P<0.001). CONCLUSIONS: MMD was characterized by concentric
      enhancement on bilateral distal internal carotid arteries and shrinkage of middle
      cerebral artery, regardless of symptoms.

PMID- 24947298
TI  - New knowledge and evidence for better leadership.
AB  - The Canadian healthcare system is increasingly complex and more difficult to
      manage with each passing decade - a situation compounded by near-constant change
      in health authority structures, interprofessional teamwork and conflict, the
      actions and decisions of senior administrators and government officials, changing
      public demographics and consumer expectations of the healthcare system, and the
      implementation of new knowledge, evidence and innovation. Through these changes -
      or despite them - nurses remain the largest group of healthcare providers at the
      interface of the healthcare system and the patient/client. Nurses must continue
      working with individuals and families to improve health outcomes while managing
      through systems changes and translating them into everyday work settings for
      themselves and their clients. 

PMID- 24947299
TI  - Canada's First Nurse Practitioner-Led Clinic: A Case Study in Healthcare
      Innovation.
AB  - Canada's first nurse practitioner-led clinic opened in 2007 after a period of
      intense lobbying. The development of this clinic has received a great deal of
      attention in the nursing world and among the general public, but the factors that
      enabled it have not been examined. The antecedents outlined in healthcare
      innovation concept analysis - including leadership, financial considerations,
      idea generation, teamwork, culture and demand - provide a framework for
      examination of the campaign for the nurse practitioner-led clinic. This review
      demonstrates the complex interplay of factors that drive healthcare innovation
      and expands understanding of the leadership and change competencies of the
      advanced practice nurse. 

PMID- 24947300
TI  - Working in Canada or the United States: perceptions of canadian nurses living in
      a border community.
AB  - Recruitment and retention of registered nurses is a critical issue facing nursing
      leaders. Global shortages of nurses have been projected over the next decade.
      This study used the theoretical framework of push and pull factors to identify
      influences on nurses' decision to select work in either their home community or a
      cross-border community, when that opportunity was available to them. Registered
      nurses living along the southwest border of Ontario were identified with the
      assistance of the College of Nurses of Ontario (CNO) and surveyed to determine
      the factors that influenced their decision to work in Canada or the United
      States, as well as their intent to remain in their current workplace. Measures
      included demographic information, reasons for selection of employment, and work
      environment factors relating to nurses' jobs, work relationships,
      scheduling/staffing, workload and attachment to their current place of
      employment. MANCOVA was used to examine differences between the two groups
      controlling for age, organizational tenure and employment status. Full-time
      employment was the greatest push factor identified by RNs, and nurses working in
      the United States were also more satisfied with the pull factors of development
      opportunities, relationships with physicians and supervisors, and scheduling
      congruence. Recommendations for recruitment and retention are discussed. 

PMID- 24947301
TI  - Conscientious objection: a call to nursing leadership.
AB  - In this paper we argue that nurse leaders need to work actively to create morally
      supportive environments for nurses in Canada that provide adequate room to
      exercise conscientious objection. Morally supportive environments engender a safe
      atmosphere to engage in open dialogue and action regarding conflict of
      conscience. The CNA's 2008 Code of Ethics for Registered Nurses has recognized
      the importance of conscientious objection in nursing and has created key
      guidelines for the registered nurse to follow when a conflict in conscience is
      being considered or declared. Nurse leaders need to further develop the
      understanding of conflicts of conscience through education, well-written
      guidelines for conscientious objection in workplaces and engagement in research
      to uncover underlying barriers to the enactment of conscientious objections. With
      advancements in technology, changing healthcare policies and increasing scope of
      practice, both reflection and dialogue on conscientious objection are critical
      for the continuing moral development of nurses in Canada. 

PMID- 24947302
TI  - Implementing Health Outcomes for Better Information and Care (HOBIC): Lessons
      from an Early Adopter Site.
AB  - Measuring patient outcomes to assess quality and to support evidence-based
      decision-making has gained momentum over the last two decades. In Ontario, the
      Health Outcomes for Better Information and Care (HOBIC) initiative has become a
      part of the province's Information Management Strategy as a way to demonstrate
      the impact of nursing care on health outcomes. In fall 2006, HOBIC implementation
      began in early adopter sites with the goal of sharing lessons learned with other
      healthcare providers and organizations. This action learning study was undertaken
      in one of the early adopter sites to gain a greater understanding of the factors
      that support, or fail to support, the integration of HOBIC into professional
      practice. Participants reported a lack of confidence using HOBIC that they
      attributed to scarce resources for ongoing education and support. Together, we
      developed a simulation workshop aimed at enhancing communication skills to
      achieve more meaningful nurse-patient interaction during the HOBIC assessment.
      This paper focuses Canadian nurse leaders' attention on the reality that
      implementing HOBIC is far from straightforward. The real challenge in HOBIC
      implementation is not mastery of the technology per se, but support for nurses
      and their ability to adapt daily practice in order to maximize its functionality.

PMID- 24947303
TI  - Amyloid-beta (1-40) restores adhesion properties of pulmonary surfactant,
      counteracting the effect of cholesterol.
AB  - A pulmonary surfactant (PS) is a thin lipid-protein film covering the surface of
      the lung alveoli at the air/liquid interface. The primary purpose of a PS is to
      control the surface tension of the air/liquid interface and to reduce the work of
      breathing. High levels of cholesterol in a PS are associated with life
      threatening acute respiratory distress syndrome (ARDS) and acute lung injury
      (ALI). Finding therapeutics to counteract the effect of cholesterol in a PS is a
      matter of contemporary research. In our earlier work, we showed that the addition
      of amyloid-beta (1-40) (Abeta40), the protein implicated in Alzheimer's disease,
      can reverse the detrimental effects of cholesterol in surfactants by improving
      multilayer formation and restoring PS surface active properties. We hypothesized
      that this phenomenon was due to Abeta40 improving adhesion properties of a
      surfactant. In this work we used atomic force spectroscopy to demonstrate that
      Abeta40 counteracts the adhesive properties of a PS compromised by high levels of
      cholesterol in a PS and helps to restore the functionality of a PS. 

PMID- 24947304
TI  - Fibrin, a scaffold material for islet transplantation and pancreatic endocrine
      tissue engineering.
AB  - Fibrin is derived from fibrinogen during injury to produce a blood clot and thus
      promote wound repair. Composed of different domains, including Arg-Gly-Asp amino
      acid motifs, fibrin is used extensively as a hydrogel and sealant in the clinic.
      By binding to cell surface receptors like integrins and acting as a supportive 3D
      scaffold, fibrin has been useful in promoting cell differentiation,
      proliferation, function, and survival. In particular, fibrin has been able to
      maintain islet cell architecture, promote beta cell insulin secretion, and islet
      angiogenesis, as well as inducing a protective effect against cell death. During
      islet transplantation, fibrin improved neovascularization and islet function.
      These improvements resulted in reduced number of transplanted islets necessary to
      reverse diabetes. Therefore, fibrin, as a biocompatible and biodegradable
      scaffold, should be considered during subcutaneous islet transplantation and beta
      cell expansion in vitro to ensure maintenance of islet cell function,
      proliferation, and survival to develop effective cell-based therapies for the
      treatment of diabetes. 

PMID- 24947305
TI  - Regulation of PKA activity by an autophosphorylation mechanism in Saccharomyces
      cerevisiae.
AB  - PKA (cAMP-dependent protein kinase) activity, as well as that of other AGC
      members, is regulated by multiple phosphorylations of its catalytic subunits. In
      Saccharomyces cerevisiae, the PKA regulatory subunit is encoded by the gene BCY1,
      and the catalytic subunits are encoded by three genes: TPK1, TPK2 and TPK3.
      Previously, we have reported that, following cAMP/PKA pathway activation, Tpk1
      increases its phosphorylation status. Now, in vivo genetic and in vitro
      experiments indicate an autophosphorylation mechanism for Tpk1. Using array
      peptides derived from Tpk1, we identified Ser179 as a target residue. Tpk1 is
      phosphorylated on Ser179 in vivo during glucose stimulus. Reduction of the
      activation loop Thr241 phosphorylation increases Ser179 autophosphorylation. To
      evaluate the role of phosphorylation on Ser179, we made strains expressing
      tpk1S179A or tpk1S179D as the sole PKA kinase source. Our results suggest that
      Ser179 phosphorylation increases the reactivity towards the substrate without
      affecting the formation of the holoenzyme. Phenotypic readout analysis showed
      that Ser179 phosphorylation increases in vivo PKA activity, reducing cell
      survival, stress and lifespan. Ser179 phosphorylation increases Tpk1 cytoplasmic
      accumulation in glucose-grown cells. These results describe for the first time
      that an autophosphorylation mechanism on Tpk1 controls PKA activity in response
      to glucose availability. 

PMID- 24947306
TI  - Induction of androgen formation in the male by a TAT-VDAC1 fusion peptide
      blocking 14-3-3E protein adaptor and mitochondrial VDAC1 interactions.
AB  - Low testosterone (T), a major cause of male hypogonadism and infertility, is
      linked to mood changes, fatigue, osteoporosis, reduced bone-mass index, and
      aging. The treatment of choice, T replacement therapy, has been linked with
      increased risk for prostate cancer and luteinizing hormone (LH) suppression, and
      shown to lead to infertility, cardiovascular diseases, and obesity. Alternate
      methods to induce T with lower side effects are desirable. In search of the
      mechanisms regulating T synthesis in the testes, we identified the 14-3-3E
      protein adaptor as a negative regulator of steroidogenesis. Steroidogenesis
      begins in mitochondria. 14-3-3E interacts with the outer mitochondrial membrane
      voltage-dependent anion channel (VDAC1) protein, forming a scaffold that limits
      the availability of cholesterol for steroidogenesis. We report the development of
      a tool able to induce endogenous T formation. Peptides able to penetrate testes
      conjugated to 14-3-3E site of interaction with VDAC1 blocked 14-3-3E-VDAC1
      interactions while at the same time increased VDAC1-translocator protein (18 kDa)
      interactions that induced steroid formation in rat testes, leading to increased
      serum T levels. These peptides rescued intratesticular and serum T formation in
      adult male rats treated with gonadotropin-releasing hormone antagonist, which
      dampened LH and T production. 

PMID- 24947307
TI  - Whole-exome sequencing improves mutation detection in a diagnostic epidermolysis
      bullosa laboratory.
AB  - BACKGROUND: Subtypes of inherited epidermolysis bullosa (EB) vary significantly
      in their clinical presentation and prognosis. Establishing an accurate diagnosis
      is important for genetic counselling and patient management. Current approaches
      in EB diagnostics involve skin biopsy for immunohistochemistry and transmission
      electron microscopy, and Sanger sequencing of candidate genes. Although
      informative in most cases, this approach can be expensive and laborious and may
      fail to identify pathogenic mutations in ~15% of cases. OBJECTIVES: Next
      generation DNA sequencing (NGS) technologies offer a fast and efficient
      complementary diagnostic strategy, but the value of NGS in EB diagnostics has yet
      to be explored. The aim of this study was to undertake whole-exome sequencing
      (WES) in nine cases of EB in which established diagnostic methods failed to make
      a genetic diagnosis. METHODS: Whole-exome capture was performed using genomic DNA
      from each case of EB, followed by massively parallel sequencing. Resulting reads
      were mapped to the human genome reference hg19. Potentially pathogenic mutations
      were subsequently confirmed by Sanger sequencing. RESULTS: Analysis of WES data
      disclosed biallelic pathogenic mutations in each case, with all mutations
      occurring in known EB genes (LAMB3, PLEC, FERMT1 and COL7A1). This study
      demonstrates that NGS can improve diagnostic sensitivity in EB compared with
      current laboratory practice. CONCLUSIONS: With appropriate diagnostic platforms
      and bioinformatics support, WES is likely to increase mutation detection in cases
      of EB and improve EB diagnostic services, although skin biopsy remains an
      important diagnostic investigation in current clinical practice.

PMID- 24947308
TI  - Selecting biologically informative genes in co-expression networks with a
      centrality score.
AB  - BACKGROUND: Measures of node centrality in biological networks are useful to
      detect genes with critical functional roles. In gene co-expression networks,
      highly connected genes (i.e., candidate hubs) have been associated with key
      disease-related pathways. Although different approaches to estimating gene
      centrality are available, their potential biological relevance in gene co
      expression networks deserves further investigation. Moreover, standard measures
      of gene centrality focus on binary interaction networks, which may not always be
      suitable in the context of co-expression networks. Here, I also investigate a
      method that identifies potential biologically meaningful genes based on a
      weighted connectivity score and indicators of statistical relevance. RESULTS: The
      method enables a characterization of the strength and diversity of co-expression
      associations in the network. It outperformed standard centrality measures by
      highlighting more biologically informative genes in different gene co-expression
      networks and biological research domains. As part of the illustration of the gene
      selection potential of this approach, I present an application case in zebrafish
      heart regeneration. The proposed technique predicted genes that are significantly
      implicated in cellular processes required for tissue regeneration after injury.
      CONCLUSIONS: A method for selecting biologically informative genes from gene co
      expression networks is provided, together with free open software.

PMID- 24947309
TI  - Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in
      the second near-infrared window.
AB  - In vivo fluorescence imaging in the second near-infrared window (1.0-1.7 MUm) can
      afford deep tissue penetration and high spatial resolution, owing to the reduced
      scattering of long-wavelength photons. Here we synthesize a series of low-bandgap
      donor/acceptor copolymers with tunable emission wavelengths of 1,050-1,350 nm in
      this window. Non-covalent functionalization with phospholipid-polyethylene glycol
      results in water-soluble and biocompatible polymeric nanoparticles, allowing for
      live cell molecular imaging at >1,000 nm with polymer fluorophores for the first
      time. Importantly, the high quantum yield of the polymer allows for in vivo, deep
      tissue and ultrafast imaging of mouse arterial blood flow with an unprecedented
      frame rate of >25 frames per second. The high time-resolution results in
      spatially and time resolved imaging of the blood flow pattern in cardiogram
      waveform over a single cardiac cycle (~200 ms) of a mouse, which has not been
      observed with fluorescence imaging in this window before. 

PMID- 24947310
TI  - Clathrin expression in Trypanosoma cruzi.
AB  - BACKGROUND: Clathrin-mediated vesicular trafficking, the mechanism by which
      proteins and lipids are transported between membrane-bound organelles, accounts
      for a large proportion of import from the plasma membrane (endocytosis) and
      transport from the trans-Golgi network towards the endosomal system. Clathrin
      mediated events are still poorly understood in the protozoan Trypanosoma cruzi,
      the causative agent of Chagas disease in Latin America. In this study, clathrin
      heavy (TcCHC) and light (TcCLC) chain gene expression and protein localization
      were investigated in different developmental forms of T. cruzi (epimastigotes,
      trypomastigotes and amastigotes), using both polyclonal and monoclonal antibodies
      raised against T. cruzi recombinant proteins. RESULTS: Analysis by confocal
      microscopy revealed an accumulation of TcCHC and TcCLC at the cell anterior,
      where the flagellar pocket and Golgi complex are located. TcCLC partially
      colocalized with the Golgi marker TcRAB7-GFP and with ingested albumin, but did
      not colocalize with transferrin, a protein mostly ingested via uncoated vesicles
      at the cytostome/cytopharynx complex. CONCLUSION: Clathrin heavy and light chains
      are expressed in T. cruzi. Both proteins typically localize anterior to the
      kinetoplast, at the flagellar pocket and Golgi complex region. Our data also
      indicate that in T. cruzi epimastigotes clathrin-mediated endocytosis of albumin
      occurs at the flagellar pocket, while clathrin-independent endocytosis of
      transferrin occurs at the cytostome/cytopharynx complex.

PMID- 24947311
TI  - Characterizing severe obesity in children and youth referred for weight
      management.
AB  - BACKGROUND: Severe obesity (SO) in pediatrics has become increasing prevalent in
      recent decades.The objective of our study was to examine differences in
      demographic, anthropometric, cardiometabolic, and lifestyle variables in children
      and youth with SO versus their less overweight/obese (OW/OB) peers. METHODS: A
      retrospective medical record review of 6-19 year old participants enrolled in an
      outpatient pediatric weight management clinic was conducted. SO (body mass index
      [BMI] >=99(th) percentile) and OW/OB (BMI >=85(th) and <99(th) percentile) groups
      were created according to Centers for Disease Control and Prevention definitions.
      Demographic, anthropometric, cardiometabolic and lifestyle data reported at
      baseline (pre-intervention) were retrieved. RESULTS: Of the 345 participants,
      most were girls (56.2%), Caucasian (78.7%), and had family incomes > $50,000/year
      (65.7%). The SO group (n = 161) had lower HDL-cholesterol and higher liver
      enzymes, insulin resistance and blood pressure than the OW/OB group (n = 184; all
      p < 0.01). They also reported higher total energy intakes, fewer steps/day, less
      moderate-to-vigorous physical activity, and more leisure time screen time (all p
      < 0.02) than their leaner peers. Compared to the OW/OB group, a higher proportion
      of individuals in the SO group possessed cardiometabolic risk factors, including
      high triglycerides (45.8% vs 58.5%), alanine aminotransferase (55.4% vs 81.4%),
      insulin resistance (55.6% vs 82.1%), systolic blood pressure (11.5% vs 27.3%),
      diastolic blood pressure (17.8% vs 30.0%), and low HDL-cholesterol (44.6% vs
      64.6%; all p < 0.02). Aside from the ~75% of participants (groups combined) who
      met the daily recommended intakes of grain and meat products, <50% of boys and
      girls met any of the remaining nutrition and physical activity-related
      recommendations. Compared to the OW/OB group, greater proportions of children and
      youth in the SO group failed to meet moderate-to-vigorous physical activity
      (48.4% vs 31.9%) and leisure-time-screen-time recommendations (43.4% vs 28.3%;
      both p < 0.05). CONCLUSION: Children and youth with SO have a worse
      cardiometabolic profile and less favorable lifestyle habits than their OW/OB
      peers. These differences emphasize the heightened obesity-related health risks
      associated with SO in the pediatric years.

PMID- 24947312
TI  - Combined salvage therapies for recurrent glioblastoma multiforme: evaluation of
      an interdisciplinary treatment algorithm.
AB  - Glioblastoma multiforme patients presenting with recurrence following
      multimodality therapy have limited palliative treatment options when the major
      modalities of therapy including surgery, radiochemotherapy and adjuvant
      chemotherapy have been exhausted. The authors introduce a clinical and
      radiological indication-solving algorithm and provide outcome rates of a
      glioblastoma recurrence cohort. Sixty six consecutive adult patients with
      recurrent glioblastoma who underwent a combined scheme of salvage treatments
      consisting of reoperation, high dose rate (HDR) brachytherapy and chemotherapy
      were included in this prospective study and were compared to a historical control
      group of 24 recurrent glioblastoma patients who have been treated with intensive
      temozolomide chemotherapy as the only treatment modality. Median follow-up was 32
      months (range 28-36 months). Median survival was 9 months for the entire cohort
      after salvage treatment and can be translated into a 3-month improvement in
      survival compared to the control group of patients with glioblastoma recurrence
      treated with temozolomide alone (P = 0.043). Toxicity and adverse events of
      reoperation, HDR brachytherapy combined with chemotherapy were quite favourable
      compared to intensive temomozolomide chemotherapy as the only treatment. Our
      experience suggests that a combined salvage treatment plan appears to be both
      feasible and effective and can be considered in selected patients affected by
      recurrent high grade gliomas. The authors' clinical and radiological indication
      solving algorithm may assist in providing the best possible salvage treatment for
      this difficult population.

PMID- 24947313
TI  - Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent
      glioblastoma multiforme.
AB  - The first-line treatment of glioblastoma typically consists of a maximal surgical
      resection, followed by a combination of radio-chemotherapy with temozolomide.
      There is however no consensus regarding optimal therapeutic approaches at
      relapse. The following phase II study explored the therapeutic gain obtained when
      exposing these patients to a combination of intra-arterially administered
      carboplatin and melphalan at first or second relapse as a salvage treatment in
      recurrent glioblastoma. Fifty-one consecutive patients diagnosed with
      glioblastoma were accrued and offered this treatment at first or second relapse.
      A Karnofsky score of >= 60 was required, and when appropriate, patients were
      first reoperated prior to accrual. Patients enrolled were treated every 4 weeks
      (1 cycle) for up to 12 cycles. Progression was evaluated by Macdonald criteria.
      Primary end point surrogates were overall survival from diagnosis and study
      entry. Median survival from diagnosis and study entry was 23 and 11 months,
      respectively. The median time to progression was 5.2 months. All patients
      enrolled were treated for a minimum of 2 cycles. Hematologic toxicity was
      manageable, with an 8 % of grade II neutropenia, 12 % of grade II
      thrombocytopenia and 7 % of grade III thrombocytopenia. This therapeutic strategy
      represents an adequate option in the second-line treatment of recurrent
      glioblastoma. The adjunction of an osmotic permeabilization could be considered
      to further expand delivery, and hopefully improve survival in these patients.

PMID- 24947314
TI  - Primary malignant chest wall tumors: analysis of 40 patients.
AB  - BACKGROUND: Primary chest wall tumors originate from different constructions of
      thoracic wall. We report our multidisciplinary experience on primary thoracic
      tumor resection and thoracic reconstruction, the need to additional therapy and
      evaluating prognostic factors affecting survival. METHODS: We performed a
      retrospective review of our prospectively maintained database of 40 patients
      treated for malignant primary chest wall tumor from 1989 to 2009. Patients were
      evaluated in terms of age, sex, clinical presentation, type of imaging, tissue
      diagnosis methods, pathology, surgical technique, early complications, hospital
      mortality, prevalence of recurrence and distant metastases, additional treatment,
      3 years survival and factors affecting survival. RESULTS: Male/Female (F/M) = 1,
      with median age of 43.72 years. Mass was the most common symptoms and the soft
      tissue sarcoma was the most common pathology. Resection without reconstruction
      was performed in 5 patients and Thirty-five patients (87.5%) had extensive
      resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or
      cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75%
      (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate
      was 65%. Recurrences occurred in 24 patients (60%), 14 developed local
      recurrences, and 10 developed distant metastases. The primary treatment modality
      for both local and distant recurrences was surgical resection; among them, 10
      underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung
      metastasectomy. The most common site of distant metastasis was lung (n = 7).
      Factors that affected survival were type of pathology and evidence of distant
      metastasis. CONCLUSION: Surgery with wide margin is the safe and good technique
      for treatment of primary chest wall tumors with acceptable morbidity and
      mortality.

PMID- 24947315
TI  - Editorial comment from Dr Todenhofer and Dr Schwentner to recurrence and
      progression in patients with non-muscle invasive bladder cancer: prognostic
      models including multicolor fluorescence in situ hybridization molecular grading.

PMID- 24947316
TI  - Increased risk and increased reward in coronary intervention in older patients
      with acute coronary syndrome.

PMID- 24947317
TI  - When is low-risk chest pain acceptable risk chest pain?

PMID- 24947318
TI  - High-sensitivity versus conventional troponin for management and prognosis
      assessment of patients with acute chest pain.
AB  - OBJECTIVES: High-sensitivity troponin (hs-cTn) is substituting conventional cTn
      for evaluation of chest pain. Our aim was to assess the impact on patient
      management and outcome. METHODS: A total of 1372 consecutive patients presenting
      at the emergency department with non-ST-elevation acute chest pain were divided
      into two periods according to the cTn assay used, conventional (n=699, March 2008
      to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies
      were similar and according to guidelines. The primary endpoint was major adverse
      cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by
      unstable angina or postdischarge revascularisation). RESULTS: There were minor
      differences in baseline characteristics. In the hs-cTn period, more patients
      elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs
      55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer
      patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and,
      therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6
      months, 135 patients suffered MACE, including 54 deaths. After adjusting for a
      Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99;
      95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95),
      though the risk of longer hospitalisation stay increased at the index episode
      (OR=1.35, 95% CI 1.07 to 1.71, p=0.02). CONCLUSIONS: hs-cTn simplified chest pain
      triage on avoiding a more complex evaluation with non-invasive tests in the chest
      pain unit, but prompted longer hospitalisations and more invasive procedures
      without impacting on the 6-month outcomes.

PMID- 24947319
TI  - Prognostic impact of beta-blocker use in patients with stable coronary artery
      disease.
AB  - OBJECTIVE: To assess the association of beta-blocker use with cardiovascular
      mortality in patients with stable coronary artery disease (CAD). METHODS: We
      analysed the data of 4184 outpatients included in a prospective cohort study on
      stable CAD. Two groups were formed based on beta-blocker use at enrolment. Two
      propensity score analyses were performed to control for differences in
      covariates: one with adjustment among the entire cohort, and the other with
      propensity score matching. The outcome variable was cardiovascular mortality
      after a 2-year follow-up. RESULTS: There were 3320 patients with beta-blocker
      use. Younger age, hypertension, diabetes, prior myocardial infarction,
      multivessel CAD, prior coronary revascularisation, prior stroke, prior
      hospitalisation for heart failure and a low LVEF were associated with beta
      blocker use. Clinical follow-up data were obtained for 4149 patients (99.2%).
      When adjusted on propensity score, beta-blocker use was associated with a HR for
      cardiovascular mortality of 0.64 (0.42-0.98) in the whole cohort (p=0.04). After
      one-to-one propensity score matching, both groups (n=839 in each group) were well
      matched on covariates. The cardiovascular mortality rate in the propensity
      matched cohort was significantly lower in patients with beta-blocker use with a
      HR of 0.43 (0.22-0.82) (p=0.011). Non-cardiovascular mortality was similar in
      both groups. These results were consistent across different subgroups.
      CONCLUSIONS: In this observational study of patients with stable CAD, the use of
      beta-blockers was associated with a lower risk of cardiovascular mortality.

PMID- 24947320
TI  - A multiple sclerosis drug sheds light on astrocyte biology.

PMID- 24947322
TI  - Recovery of altered neuromuscular junction morphology and muscle function in mdx
      mice after injury.
AB  - Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which
      weakness, increased susceptibility to muscle injury, and inadequate repair
      underlie the pathology. While most attention has focused within the muscle fiber,
      we recently demonstrated significant alterations in the neuromuscular junction
      (NMJ) morphology and resulting neuromuscular transmission failure (NTF) 24 h
      after injury in mdx mice (murine model for DMD). Here we determine the
      contribution of NMJ morphology and NTF to the recovery of muscle contractile
      function post-injury. NMJ morphology and NTF rates were assessed day 0
      (immediately after injury) and days 1, 7, 14 and 21 after quadriceps injury.
      Eccentric injury of the quadriceps resulted in a significant loss of maximal
      torque in both WT (39 +/- 6 %) and mdx (76 +/- 8 %) with a full recovery in WT by
      day 7 and in mdx by day 21. Post-injury alterations in NMJ morphology and NTF
      were found only in mdx, were limited to days 0 and 1, and were independent of
      changes in MuSK or AChR expression. Such early changes at the NMJ after injury
      are consistent with mechanical disruption rather than newly forming NMJs.
      Furthermore, we show that the dense microtubule network that underlies the NMJ is
      significantly reduced and disorganized in mdx compared to WT. These structural
      changes at the NMJ may play a role in the increased NMJ disruption and the
      exaggerated loss of nerve-evoked muscle force seen after injury to dystrophic
      muscles.

PMID- 24947321
TI  - Tyrosine nitration as mediator of cell death.
AB  - Nitrotyrosine is used as a marker for the production of peroxynitrite and other
      reactive nitrogen species. For over 20 years the presence of nitrotyrosine was
      associated with cell death in multiple pathologies. Filling the gap between
      correlation and causality has proven to be a difficult task. Here, we discuss the
      evidence supporting tyrosine nitration as a specific posttranslational
      modification participating in the induction of cell death signaling pathways.

PMID- 24947323
TI  - The F-box protein FBXO7 positively regulates bone morphogenetic protein-mediated
      signaling through Lys-63-specific ubiquitination of neurotrophin receptor
      interacting MAGE (NRAGE).
AB  - Parkinson's disease (PD) is characterized by progressive midbrain dopaminergic
      neuron degeneration and the formation of intracellular protein aggregates,
      referred to as Lewy bodies. F-box only protein 7 (FBXO7) gene mutations are
      closely associated with progression of the autosomal recessive form of familial
      PD. FBXO7 encodes a component of Skp1, cullin, F-box ubiquitin ligase complexes;
      however, its cellular targets, including substrates and regulators, are not yet
      clarified. To identify potential substrates of FBXO7, we performed a yeast two
      hybrid screen of a human fetal brain library and identified neurotrophin receptor
      interacting MAGE protein (NRAGE) as a novel FBXO7-binding partner. We found that
      FBXO7 interacts with NRAGE and mediates Lys-63-linked poly-ubiquitination of
      NRAGE in mammalian cells. FBXO7 overexpression accelerates formation of NRAGE
      TAK1-TAB1 complexes, whereas FBXO7 knockdown correspondingly decreases complex
      formation. In addition, BMP4 stimulation enhances NRAGE ubiquitination through
      FBXO7 and facilitates endogenous NRAGE-TAK1-TAB1 complex formation. Furthermore,
      FBXO7 positively regulates formation of the BMP receptor-NRAGE-TAK1-TAB1 complex,
      and up-regulates NF-kappaB activity. Taken together, our results suggest that
      FBXO7 affects BMP4-mediated signaling through proteasome-independent
      ubiquitination of NRAGE and augments formation of downstream signaling
      components. 

PMID- 24947325
TI  - Uterine necrosis and lumbosacral-plexopathy following pelvic vessel embolization
      for postpartum haemorrhage: report of two cases and review of literature.
AB  - We are reporting two cases of uterine necrosis and lumbosacral-plexopathy in
      patients, who underwent pelvic vessel embolization (PVE) following postpartum
      hemorrhage. Embolization was performed with gelfoam slurry, polyvinyl alcohol
      (PVA) particles and coil in one patient and with gelfoam slurry only, in second
      patient. Both patients had lower limbs weakness and had persistent fever in the
      postembolization period. Nerve conduction study in both were suggestive of common
      peroneal and tibial neuropathy. An ultrasonography and computed tomography of
      abdomen and pelvis revealed bulky uterus with no identifiable endometrium and
      multiple air foci in subendometrial region suggestive of uterine necrosis,
      confirmed later by histology of expelled uterine mass. Lumbosacral ischemia
      resulting in paraparesis and uterine necrosis presenting as longstanding fever
      after embolization are extremely rare but overwhelming complications of
      embolization. Only 19 cases of uterine necrosis and <10 cases of lumbosacral
      plexopathy have been reported in the literature. The overall effectiveness of PVE
      is high in treatment of obstetric hemorrhage with low complication rate and
      highly selective PVE may further prevent these complication. To the best of our
      knowledge the co-existing uterine necrosis and lumbosacral plexopathy secondry to
      PVE has not been described prevoiusly in patients with postpartum hemorrhage.
      Both patients recovered with conservative management. 

PMID- 24947327
TI  - Assessment of pleiotropic transcriptome perturbations in Arabidopsis engineered
      for indirect insect defence.
AB  - BACKGROUND: Molecular characterization is an essential step of risk/safety
      assessment of genetically modified (GM) crops. Holistic approaches for molecular
      characterization using omics platforms can be used to confirm the intended impact
      of the genetic engineering, but can also reveal the unintended changes at the
      omics level as a first assessment of potential risks. The potential of omics
      platforms for risk assessment of GM crops has rarely been used for this purpose
      because of the lack of a consensus reference and statistical methods to judge the
      significance or importance of the pleiotropic changes in GM plants. Here we
      propose a meta data analysis approach to the analysis of GM plants, by measuring
      the transcriptome distance to untransformed wild-types. RESULTS: In the
      statistical analysis of the transcriptome distance between GM and wild-type
      plants, values are compared with naturally occurring transcriptome distances in
      non-GM counterparts obtained from a database. Using this approach we show that
      the pleiotropic effect of genes involved in indirect insect defence traits is
      substantially equivalent to the variation in gene expression occurring naturally
      in Arabidopsis. CONCLUSION: Transcriptome distance is a useful screening method
      to obtain insight in the pleiotropic effects of genetic modification.

PMID- 24947328
TI  - Surgical outcome of malignant primary bone tumours in elderly and very elderly
      patients.
AB  - PURPOSE: Elderly patients with bone cancer are thought to have poorer access to
      specialist treatment and therefore suboptimal outcome. The aim of this study was
      to review the clinical course, outcome and survivorship in geriatric patients
      with primary bone tumours. METHODS: We analysed 66 consecutive patients aged 60
      years or older who were surgically treated for primary bone tumours between 1997
      and 2012. The cohort was divided into two groups: elderly (60-70 years, n = 31)
      and very elderly (>70 years, n = 35). Clinicopathologic characteristics,
      treatment, outcome and survival were analysed. The mean follow up was 58.5 months
      (range two to 188). RESULTS: There were 51 chondrosarcomas (grade I, n = 29;
      grade II, n = 15; grade III, n = 7), ten osteosarcomas and four of other primary
      malignant bone tumours. Twenty-three prostheses for joint reconstruction were
      implanted; procedures involving the transposition of free vascularised flaps were
      performed in six patients. Seven patients had amputation as a primary procedure,
      four in the elderly and three in the very elderly group. Local recurrence was
      recorded in eight cases (12.1%). Secondary surgery was performed in nine (13.6%)
      patients (six recurrences, two haematomas, one deep infection). At final follow
      up, 77.3% of patients were alive (elderly 83.9%, very elderly 71.4%) and there
      was no significant difference in the five-year survival rates between both
      groups. CONCLUSIONS: Elderly and very elderly patients with bone tumours receive
      satisfactory treatment and achieve good surgical outcome. Treatment decisions in
      the geriatric population should not be influenced by age alone.

PMID- 24947326
TI  - Wild-type ALK and activating ALK-R1275Q and ALK-F1174L  mutations upregulate Myc
      and initiate tumor formation in  murine neural crest progenitor cells.
AB  - The anaplastic lymphoma kinase (ALK) gene is overexpressed, mutated or amplified
      in most neuroblastoma (NB), a pediatric neural crest-derived embryonal tumor. The
      two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB
      tumorigenesis in mouse models, and cooperate with MYCN in the oncogenic process.
      However, the precise role of activating ALK mutations or ALK-wt overexpression in
      NB tumor initiation needs further clarification. Human ALK-wt, ALK-F1174L, or ALK
      R1275Q were stably expressed in murine neural crest progenitor cells (NCPC), MONC
      1 or JoMa1, immortalized with v-Myc or Tamoxifen-inducible Myc-ERT, respectively.
      While orthotopic implantations of MONC- 1 parental cells in nude mice generated
      various tumor types, such as NB, osteo/ chondrosarcoma, and undifferentiated
      tumors, due to v-Myc oncogenic activity, MONC-1-ALK-F1174L cells only produced
      undifferentiated tumors. Furthermore, our data represent the first demonstration
      of ALK-wt transforming capacity, as ALK-wt expression in JoMa1 cells, likewise
      ALK-F1174L, or ALK-R1275Q, in absence of exogenous Myc-ERT activity, was
      sufficient to induce the formation of aggressive and undifferentiated neural
      crest cell-derived tumors, but not to drive NB development. Interestingly, JoMa1
      ALK tumors and their derived cell lines upregulated Myc endogenous expression,
      resulting from ALK activation, and both ALK and Myc activities were necessary to
      confer tumorigenic properties on tumor-derived JoMa1 cells in vitro.

PMID- 24947329
TI  - Clinical outcomes and complications of a collagen meniscus implant: a systematic
      review.
AB  - PURPOSE: The purpose of this systematic review was to summarise and evaluate the
      clinical outcomes of the collagen meniscus implant (CMI) and its complication and
      failure rates. These data were then used to evaluate the results of the CMI at
      different follow-up time periods and investigate possible differences in the
      behaviour of lateral and medial CMI. METHODS: A comprehensive search was
      performed in PubMed, MEDLINE, CINAHL, Cochrane, EMBASE and Google Scholar
      databases using various combinations of the following keywords: "collagen
      meniscus implant" or "collagen meniscal implant". All studies evaluating medial
      or lateral CMI using the Lysholm score, visual analogue scale (VAS) for pain,
      Tegner activity scale and subjective or objective International Knee
      Documentation Committee (IKDC) scores were included in the systematic review.
      RESULTS: Eleven studies were included in the systematic review. The pooled number
      of patients involved in CMI surgery were 396 (90.2 % medial, 9.8 % lateral), with
      a mean age at surgery of 37.8 years. Concomitant procedures were present in 48.8
      % of patients; most of them were anterior cruciate ligament (ACL) reconstruction,
      high tibial osteotomy (HTO) and microfractures. The Lysholm score and VAS for
      pain showed an improvement at six months up to ten years. No noticeable
      differences were present comparing short-term values of Lysholm score between
      medial and lateral CMI. The Tegner activity level reached its peak at 12 months
      after surgery and showed a progressive decrease through five and ten years post
      CMI implantation, however always remaining above the pre-operative level. Only a
      few knees were rated as "nearly abnormal" or "abnormal" at IKDC grading at all
      follow-up evaluations. CONCLUSIONS: The CMI could produce good and stable
      clinical results, particularly regarding knee function and pain, with low rates
      of complications and reoperations.

PMID- 24947331
TI  - The low-recombining pericentromeric region of barley restricts gene diversity and
      evolution but not gene expression.
AB  - The low-recombining pericentromeric region of the barley genome contains roughly
      a quarter of the genes of the species, embedded in low-recombining DNA that is
      rich in repeats and repressive chromatin signatures. We have investigated the
      effects of pericentromeric region residency upon the expression, diversity and
      evolution of these genes. We observe no significant difference in average
      transcript level or developmental RNA specificity between the barley
      pericentromeric region and the rest of the genome. In contrast, all of the
      evolutionary parameters studied here show evidence of compromised gene evolution
      in this region. First, genes within the pericentromeric region of wild barley
      show reduced diversity and significantly weakened purifying selection compared
      with the rest of the genome. Second, gene duplicates (ohnolog pairs) derived from
      the cereal whole-genome duplication event ca. 60MYa have been completely
      eliminated from the barley pericentromeric region. Third, local gene duplication
      in the pericentromeric region is reduced by 29% relative to the rest of the
      genome. Thus, the pericentromeric region of barley is a permissive environment
      for gene expression but has restricted gene evolution in a sizeable fraction of
      barley's genes. 

PMID- 24947333
TI  - Clinical importance of duplicated internal jugular vein.

PMID- 24947332
TI  - Association of single nucleotide polymorphisms in cell cycle regulatory genes
      with oral cancer susceptibility.
AB  - Alterations in the regulation of the cell cycle are strongly linked to
      tumorigenesis, so genetic variants in genes critical to control of the cycle are
      good candidates to have their association with susceptibility to oral cancer
      assessed. In this hospital-based, case-control study of 445 patients who had been
      newly-diagnosed with oral cancer and 449 unaffected controls, we used a
      multigenic approach to examine the associations among a panel of 10 selected
      polymorphisms in the pathway of the cell cycle that were possibly susceptible to
      oral cancer. Six of 9 single nucleotide polymorphisms in the cell cycle showed
      significant risks for oral cancer, the highest risk being evident for p27
      (rs34329; Odds ratio 3.05, 95% CI 2.12 to 4.40). A significant risk of oral
      cancer was also evident for individual polymorphisms of cyclin E (rs1406), cyclin
      H (rs3093816), cyclin D1-1 (rs647451), cyclin D2 (rs3217901) and Rb1-2
      (rs3092904). The risk of oral cancer increased significantly as the number of
      unfavourable genotypes in the pathway increased, and so the results point to a
      stronger combined effect of polymorphisms in important cell cycle regulatory
      genes on predisposition to oral cancer.

PMID- 24947324
TI  - Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair
      pathways in oxidative stress.
AB  - To maintain genome stability, cells have evolved various DNA repair pathways to
      deal with oxidative DNA damage. DNA damage response (DDR) pathways, including ATM
      Chk2 and ATR-Chk1 checkpoints, are also activated in oxidative stress to
      coordinate DNA repair, cell cycle progression, transcription, apoptosis, and
      senescence. Several studies demonstrate that DDR pathways can regulate DNA repair
      pathways. On the other hand, accumulating evidence suggests that DNA repair
      pathways may modulate DDR pathway activation as well. In this review, we
      summarize our current understanding of how various DNA repair and DDR pathways
      are activated in response to oxidative DNA damage primarily from studies in
      eukaryotes. In particular, we analyze the functional interplay between DNA repair
      and DDR pathways in oxidative stress. A better understanding of cellular response
      to oxidative stress may provide novel avenues of treating human diseases, such as
      cancer and neurodegenerative disorders. 

PMID- 24947334
TI  - Crohn's disease outpatients treated with adalimumab have an earlier secondary
      loss of response and requirement for dose escalation compared to infliximab: a
      real life cohort study.
AB  - BACKGROUND: The efficacy of anti-tumor necrosis factor alpha agents in
      maintaining remission in Crohn's disease may wane over time, leading to secondary
      loss of response that can often be overcome with dose escalation. Comparison of
      secondary loss of response of adalimumab and infliximab during long-term
      treatment of CD in a real-life IBD clinic has not been previously evaluated.
      METHODS: A retrospective cohort study was conducted evaluating outpatients with
      CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and
      who experienced a secondary loss of response. All infliximab-treated patients
      were anti-TNF naive. Adalimumab-treated patients were stratified by prior anti
      TNF exposure. Kaplan-Meier analysis was conducted to compare time to loss of
      response. RESULTS: 218 CD patients met inclusion criteria (117 infliximab, 101
      adalimumab). Median follow-up duration was 170.0weeks for infliximab and
      122.0weeks for adalimumab (p=0.61). The proportion of patients with secondary
      loss of response was similar for infliximab-treated - 51.3% (60/117) compared to
      adalimumab patients naive to anti-TNF therapy - 60.5% (23/38) (p=0.32), and
      adalimumab patients with prior anti-TNF exposure - 65.1% (41/63) (p=0.08). Median
      time to secondary loss of response was longer for infliximab patients (99.3wk,
      IQR 55.7-168.5) compared to both adalimumab patients naive to anti-TNF therapy
      (58.9wk, IQR 29.0-85.7) (p=0.03), and adalimumab patients with prior anti-TNF
      exposure (52.7wk, IQR 20.1-85.0) (p<0.001). CONCLUSIONS: Over 50% of CD patients
      treated with infliximab and adalimumab develop secondary loss of response. Time
      to loss of response was shorter in patients treated with adalimumab compared to
      those treated with infliximab. Prior anti-TNF exposure further accelerated time
      to loss of response.

PMID- 24947335
TI  - Quantitative evaluation of biliary elimination of gadoxetate, a magnetic
      resonance imaging contrast agent, via geometrical isomer-specific transporting
      system in rats.
AB  - Gadoxetate, a magnetic resonance imaging contrast agent, is eliminated into bile.
      Gadoxetate geometrical isomers are chromatographically classified into two groups
      by differences between their ionic states (GIs-I and GIs-II; 65:35 w/w); however,
      the elimination mechanism of each isomer in vivo remains controversial. Thus, the
      contribution of carrier-mediated transport systems on the biliary elimination of
      gadoxetate was examined. Gadoxetate was injected intravenously into rats, and the
      time courses of the plasma concentrations and biliary elimination of GIs-I and
      GIs-II were examined by high-performance liquid chromatography techniques. The
      results showed that 34.7% of GIs-I (GIs-I(s); 22.6% of gadoxetate) was quickly
      eliminated into bile within 30 min after injection. The contents of the residual
      GIs-I (GIs-I(r)) and GIs-II in plasma similarly decreased according to a first
      order elimination process (t1/2=23-27 min), and 64.0% of GIs-I(r) and GIs-II
      (49.6% of gadoxetate) was eliminated into the bile within 2 h after injection.
      There was no significant difference between the elimination half-lives of GIs
      I(r) and GIs-II in rats. In conclusion, the geometrical isomer with specific
      conformation corresponding to 22.6% of gadoxetate was eliminated into bile in
      rats via a carrier-mediated transport system no later than 30 min after
      intravenous injection.

PMID- 24947336
TI  - Tobacco NUP1 transports both tobacco alkaloids and vitamin B6.
AB  - The purine permeases (PUPs) constitute a large plasma membrane-localized
      transporter family in plants that mediates the proton-coupled uptake of
      nucleotide bases and their derivatives, such as adenine, cytokinins, and
      caffeine. A Nicotiana tabacum (tobacco) PUP-family transporter, nicotine uptake
      permease 1 (NtNUP1), was previously shown to transport tobacco alkaloids and to
      affect both nicotine biosynthesis and root growth in tobacco plants. Since
      Arabidopsis PUP1, which belongs to the same subclade as NtNUP1, was recently
      reported to transport pyridoxine and its derivatives (vitamin B6), it was of
      interest to examine whether NtNUP1 could also transport these substrates. Direct
      uptake measurements in the yeast Saccharomyces cerevisiae demonstrated that
      NtNUP1 efficiently promoted the uptake of pyridoxamine, pyridoxine, anatabine,
      and nicotine. The naturally occurring (S)-isomer of nicotine was preferentially
      transported over the (R)-isomer. Transport studies using tobacco BY-2 cell lines
      overexpressing NtNUP1 or PUP1 showed that NtNUP1, similar to PUP1, transported
      various compounds containing a pyridine ring, but that the two transporters had
      distinct substrate preferences. Therefore, the previously reported effects of
      NtNUP1 on tobacco physiology might involve bioactive metabolites other than
      tobacco alkaloids. 

PMID- 24947337
TI  - Stress-induced expression of NICOTINE2-locus genes and their homologs encoding
      Ethylene Response Factor transcription factors in tobacco.
AB  - Plants have evolved diverse defense metabolites as adaptations to biotic and
      abiotic stresses. The defense alkaloid nicotine is produced in Nicotiana tabacum
      (tobacco) and its biosynthesis is elicited by jasmonates in the roots. At least
      seven jasmonate-responsive genes that encode transcription factors of the
      Ethylene Response Factor (ERF) family are clustered at the nicotine-regulatory
      locus NICOTINE2 (NIC2) in the tobacco genome. A subset of the NIC2-locus ERFs and
      their homologs, including ERF189 and ERF199, have been shown to be most effective
      in controlling nicotine biosynthetic pathway genes. Herein reported is that the
      ERF genes of this group, other than ERF189 and ERF199, were strongly induced by
      NaCl in tobacco hairy roots, although salt stress had no effect on expression of
      nicotine biosynthesis genes. Abscisic acid and osmotic stress also increased
      expression of a subset of these NaCl-inducible ERF genes. Promoter expression
      analysis in transgenic tobacco hairy roots confirmed that while methyl jasmonate
      (MJ) activated the promoters of ERF29, ERF210 and ERF199, salt stress up
      regulated the promoters of only ERF29 and ERF210, but not ERF199. The protein
      biosynthesis inhibitor cycloheximide induced expression of the ERFs, and
      simultaneous addition of MJ and cycloheximide showed synergistic effects. These
      results indicate that, after several gene duplication events, the NIC2-locus ERFs
      and possibly their homologs appear to have diverged in their responses to
      jasmonates and various environmental inputs, including salt stress, and may have
      evolved to regulate distinct metabolic processes and cellular responses. 

PMID- 24947338
TI  - Phytotoxic cis-clerodane diterpenoids from the Chinese liverwort Scapania
      stephanii.
AB  - Five cis-clerodane diterpenoids, stephanialides A-E, along with seven known cis
      clerodanes, scaparvins A-C, parvitexins B and C, 3-chloro-4-hydroxy-parvitexin A,
      and scapanialide B, were isolated from the Chinese liverwort Scapania stephanii.
      Their structures were established unequivocally on the basis of spectroscopic
      data. The absolute configuration of stephanialide A was determined by analysis of
      CD data using the octant rule. Phytotoxic activity evaluation showed that this
      type of diterpenoids can significantly inhibit root elongation of the seeds of
      Arabidopsis thaliana, Lepidium sativum and Brassica pekinensis. 

PMID- 24947339
TI  - UHPLC-MS/MS based target profiling of stress-induced phytohormones.
AB  - Stress-induced changes in phytohormone metabolite profiles have rapid effects on
      plant metabolic activity and growth. The jasmonates (JAs) are a group of fatty
      acid-derived stress response regulators with roles in numerous developmental
      processes. To elucidate their dual regulatory effects, which overlap with those
      of other important defence-signalling plant hormones such as salicylic acid (SA),
      abscisic acid (ABA) and indole-3-acetic acid (IAA), we have developed a highly
      efficient single-step clean-up procedure for their enrichment from complex plant
      matrices that enables their sensitive quantitative analysis using hyphenated mass
      spectrometry technique. The rapid extraction of minute quantities of plant
      material (less than 20mg fresh weight, FW) into cold 10% methanol followed by one
      step reversed-phase polymer-based solid phase extraction significantly reduced
      matrix effects and increased the recovery of labile JA analytes. This extraction
      and purification protocol was paired with a highly sensitive and validated ultra
      high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)
      method and used to simultaneously profile sixteen stress-induced phytohormones in
      minute plant material samples, including endogenous JA, several of its
      biosynthetic precursors and derivatives, as well as SA, ABA and IAA. 

PMID- 24947340
TI  - Clinical significance of prognosis using the neutrophil-lymphocyte ratio and
      erythrocyte sedimentation rate in patients undergoing radical nephroureterectomy
      for upper urinary tract urothelial carcinoma.
AB  - OBJECTIVES: To evaluate the clinical significance of preoperative erythrocyte
      sedimentation rate (ESR) and neutrophil-lymphocyte ratio (NLR) as prognostic
      factors in patients undergoing radical nephroureterectomy for upper tract
      urothelial carcinoma (UTUC). PATIENTS AND METHODS: A total of 410 patients were
      retrospectively reviewed. An elevated NLR was defined as >=2.5 and a normal ESR
      was considered to be in the range of 0-22 mm/h in men and 0-27 mm/h in women.
      Patients were divided into three groups: those with ESR and NLR in the normal
      range (group 0, n = 168), those with either elevated ESR or elevated NLR (group
      I, n = 169), and those with both elevated ESR and elevated NLR (group II, n =
      73). RESULTS: The median patient age was 64 years and the median follow-up
      duration was 40.2 months. In all, 35.6 and 41.2% of patients had elevated NLRs
      and ESRs, respectively. Group II was associated with advanced tumour status in
      terms of size, grade, stage, lymph node and margin status (P < 0.05).
      Preoperative ESR (hazard ratio [HR] 1.784, 95% confidence interval [CI] 1.173
      2.712), NLR (HR 1.704, 95% CI 1.136-2.556), and prognostic grouping (HR 2.285,
      95% CI 1.397-3.737 for group I; HR 2.962, 95% CI 1.719-5.102 for group II) were
      independent predictors of progression-free survival (PFS) in the multivariate
      model (P < 0.05). Prognostic grouping was also an independent prognostic factor
      for cancer-specific survival (CSS) and overall survival (OS). Time-dependent area
      under the receiver-operating characteristic curves showed that NLR plus ESR had a
      greater diagnostic value than NLR alone regarding oncological outcomes (P <
      0.05). CONCLUSIONS: Prognostic grouping using ESR and NLR was identified as an
      independent prognostic marker in patients with UTUC. The addition of ESR improved
      the prognostic value of NLR alone in predicting oncological outcomes. The
      combination of preoperative ESR and NLR might be a new prediction tool in
      patients with UTUC after radical nephroureterectomy.

PMID- 24947341
TI  - Comorbidity in heart failure. Results of the Spanish RICA Registry.
AB  - BACKGROUND: We sought to identify the comorbidities associated with heart failure
      (HF) in a non-selected cohort of patients, and its influence on mortality and
      rehospitalization. DESIGN AND METHODS: Data were obtained from the 'Registro de
      Insuficiencia Cardiaca' (RICA) of the Spanish Society of Internal Medicine. The
      registry includes patients prospectively admitted in Internal Medicine units for
      acute HF. Variables included in Charlson Index (ChI) were collected and analysed
      according to age, gender, left ventricular ejection fraction (LVEF) and Barthel
      Index. The primary end point of study was the likelihood of rehospitalization and
      death for any cause during the year after discharge. RESULTS: We included 2051
      patients, mean age 78 and 53% females. LVEF was ? 50% in 59.1% of the cohort.
      There was a high degree of dependency as measured by Barthel Index (14.8 % had an
      index <= 60). Mean ChI was 2.91 (SD +/- 2.4). The most frequent comorbidities
      included in ChI were diabetes mellitus (44.3%), chronic renal impairment (30.8%)
      and chronic obstructive pulmonary disease (COPD) (27.4%). Age, myocardial
      infarction, peripheral artery disease, dementia, COPD, chronic renal impairment
      and diabetes with target-organ damage were all identified as independent
      prognostic factors for the combined end point of rehospitalization and death at 1
      year. However, if multivariate analysis was done including ChI, only this
      remained as an independent prognostic factor for the combined end point (P <
      0.001). CONCLUSIONS: HF is a comorbid condition. ChI is a simple and feasible
      tool for estimating the burden of comorbidities in such population. We believe
      that a holistic approach to HF would improve prognosis and the relief the
      pressure exerted on public health services.

PMID- 24947342
TI  - New concepts in DNA methylation.
AB  - The widely-cited model of maintenance of DNA methylation at CpG sites implies
      that DNA methylation is introduced by the Dnmt3 de novo DNA methyltransferases
      during early development, and methylation at hemimethylated CpG sites is
      specifically maintained by the Dnmt1 maintenance methyltransferase. However,
      substantial experimental evidence from the past decade indicates that this simple
      model needs to be revised. DNA methylation can be described by a dynamic
      stochastic model, in which DNA methylation at each site is determined by the
      local activity of DNA methyltransferases (Dnmts), DNA demethylases, and the DNA
      replication rate. Through the targeting and regulation of these enzymes, DNA
      methylation is controlled by the network of chromatin marks. 

PMID- 24947343
TI  - Lipid suppression for brain MRI and MRSI by means of a dedicated crusher coil.
AB  - PURPOSE: Lipid suppression in MR brain imaging and spectroscopy has been a long
      standing problem for which various techniques have been developed. Most methods
      are based on inversion recovery or spatially or spectrally selective excitation
      of the lipid signal followed by dephasing. All techniques require additional RF
      pulses, gradient crushers and delays, which increase the duration and complexity
      of sequences. In addition, the lipid signal is poorly shimmed, and is composed of
      different resonance frequencies that have different relaxation properties.
      METHODS: In this work, a novel approach for suppression of extra cranial lipids
      is presented, by means of an outer volume crusher coil. It is based on the
      principle of surface spoiling gradients, which generate a very local and
      inhomogeneous magnetic field in the outer layer of the head, and thereby destroys
      the phase coherence of the extra cranial signals. RESULTS: Dephasing of the
      signal can be incorporated in almost any sequence because it requires only a
      short pulse of the coil, and does not require additional RF pulses or delays.
      Examples of lipid suppression are shown in both gradient echo imaging and
      spectroscopic imaging. CONCLUSION: Outer volume crushing allows for simple fat
      suppression and boosts scanning efficiency, which is particularly beneficial at
      ultra-high field strengths.

PMID- 24947344
TI  - Ureteroureterostomy irrespective of ureteral size or upper pole function: a
      single center experience.
AB  - OBJECTIVE: Although ureteroureterostomy (UU) is an established procedure for the
      treatment of duplex anomalies, there may be a reluctance to apply this approach
      to patients with poor upper pole function and/or marked degrees of ureteral
      dilation. METHODS: An institutional review board (IRB)-approved retrospective
      analysis of all patients undergoing UU between 2006 and present was performed.
      All patients underwent an end-to-side anastomosis with a double-J stent left in
      the lower pole ureter. Laparoscopic repairs were done 'high' and open repairs
      were done 'low'. If the upper pole ureter remained massively dilated after
      transection, the ureter was partially closed to reduce the length of the
      anastomosis. Data collected included demographics, diagnosis, surgical
      interventions, imaging studies and outcomes. RESULTS: A total of 41 patients (43
      renal units) were identified. There were 35 females and six males with an average
      age at surgery of 2.3 years (range 55 days to 15.9 years) and an average follow
      up of 2.8 years. Diagnosis included ureterocele (17), ectopic duplex ureter (25)
      and ureteral triplication (1). Thirty-six patients underwent UU only and five
      underwent UU with simultaneous lower pole reimplantation. Twelve of the 41
      patients (29%) underwent laparoscopic repair. Twelve of the 43 renal units (28%)
      required ureteral tapering, of which three were performed laparoscopically.
      Preoperative median upper pole function was 17% (0-35%). Six patients had no
      measurable function and ten had < 15%. No patient developed lower pole
      hydronephrosis in the follow-up period. There were two complications: one patient
      was found to have a post-operative ureterovesical junction (UVJ) stricture and
      the second had an anastomotic stricture. CONCLUSION: Ureteroureterostomy is a
      safe and effective technique for the reconstruction of duplex anomalies, even
      with a massively dilated and poorly functioning upper pole moiety. With no
      identifiable negative effect on the lower pole system, the concept of
      automatically removing 'dysplastic' upper pole segments can be challenged.

PMID- 24947345
TI  - Lumbotomy approach for upper urinary tract surgeries in adolescents: feasibility
      and challenges.
AB  - OBJECTIVE: The objective of this study was to assess the feasibility and
      challenges in a lumbotomy approach for performing upper urinary tract surgeries
      in adolescent children. MATERIAL AND METHODS: Fifty-five adolescent children
      underwent various upper urinary tract surgeries from 2000 to 2012. In all
      patients, the kidneys and ureters were approached via a lumbotomy incision. The
      patients' characteristics were analysed from the hospital charts. Intraoperative
      and postoperative details were gathered from individual case files. Data were
      collected regarding: age, weight, gender, diagnosis, surgical procedure,
      anaesthetic details, any intraoperative problems encountered, postoperative pain,
      time to oral feed, length of hospitalisation and any complications. RESULTS: The
      median age at surgery was 14 years (range 10-19). There were 42 boys and 13
      girls. Median weight was 41 kg (range 28-52 kg). Surgeries performed were
      pyeloplasty, pyelolithotomy, nephroureterectomy and heminephrectomy. Mean
      duration of surgery was 80 min (range 60-130 min) with no special anaesthetic
      requirements. No intraoperative problems were encountered. In all patients,
      postoperative stay was uneventful with minimal analgesic requirements and oral
      feeding was started the very next day. There were no incision-related
      complications. CONCLUSIONS: A lumbotomy incision is technically easy and safe,
      even in adolescent children, as an approach for upper urinary-tract surgeries.

PMID- 24947346
TI  - Medication cost is significantly reduced after Roux-en-Y gastric bypass in obese
      patients.
AB  - BACKGROUND: This study aims to determine the influence of Roux-en-Y gastric
      bypass (RYGB) on medication-related costs. METHODS: The study analyzed the types,
      dosages, and costs of drugs and medical devices prescribed before and after
      surgery (1, 3, 6, and 12 months and yearly thereafter) in patients who underwent
      RYGB between June 2004 and May 2010 and had an outpatient visit between December
      2009 and May 2010 at Pitie-Salpetriere University Hospital, Paris, France.
      RESULTS: The cohort included 143 patients (78 % female; mean age, 42.9 years;
      mean BMI, 48.6 kg/m(2)). Total prescription costs were significantly lower (-32
      %, p < 0.001) 1 year after RYGB compared with preoperative costs. However, the
      cost for medications to prevent RYGB side effects (in particular nutritional
      deficiencies) displayed a 36-fold increase in the first month postsurgery, but
      then decreased progressively over time. Importantly, the cost related to the
      treatment of the two most frequent obesity-related diseases significantly
      decreased 1 year after surgery. Indeed, prescription costs for treatment of type
      2 diabetes (T2D) and obstructive sleep apnea (OSA) (namely CPAP therapy
      considered as the gold standard treatment) were reduced 1 year after surgery by
      85 and by 63 % (both p < 0.001), respectively. We also observed a trend toward a
      decrease in the prescription costs of other obesity-related diseases, although it
      did not reach significance in our cohort. CONCLUSIONS: Considering medication to
      treat both obesity-related diseases and prevention of secondary effects of
      bariatric surgery, we observed that overall postoperative medication costs were
      significantly reduced one year after surgery, especially for T2D and OSA.

PMID- 24947347
TI  - Antegrade nailing evolution for proximal humeral fractures, the Telegraph
      IV((r)): a study of 67 patients.
AB  - INTRODUCTION: There are multiple surgical treatment methods for proximal humerus
      fractures (PHF), but rarely do they provide satisfactory results. The objective
      of this study was to assess radioclinical outcomes and complications in patients
      treated using a modern intramedullary nailing system the Telegraph I((r)).
      MATERIALS AND METHODS: This is an observational multicenter study cohort
      conducted between March 2008 and December 2009 on 105 patients admitted with a
      diagnosis of PHF and operated on two trauma I centers. The Neer and Articular
      Surgical neck Tuberosities classifications were used for the study. The primary
      outcome measure was the clinical Constant score. Follow-up of the patients was
      done at 6 weeks, 3 months, 6 months, 1 year, and 3 years after the procedure.
      RESULTS: A total of 67 patients (51 women and 16 men) were assessed at a mean of
      38 months. The weighted Constant score was 88%. The mean rate of complications
      was 16%. The weighted Constant scores were 84 and 95% for the 2- and 3-part
      groups, respectively. Articular 4-part fractures had an average score of 86% when
      they were valgus impacted and 67% for complex disengaged fractures. Notably, the
      complication rate was 67% for this latter group. CONCLUSIONS: Our clinical
      results support the use of this antegrade nailing for extra-articular and valgus
      impacted articular fractures. This procedure does not appear suitable for
      displaced articular fracture for which arthroplasty may be indicated by elderly.

PMID- 24947350
TI  - SIRT1 mediates the effect of GLP-1 receptor agonist exenatide on ameliorating
      hepatic steatosis.
AB  - GLP-1 and incretin mimetics, such as exenatide, have been shown to attenuate
      hepatocyte steatosis in vivo and in vitro, but the specific underlying mechanism
      is unclear. SIRT1, an NAD(+)-dependent protein deacetylase, has been considered
      as a crucial regulator in hepatic lipid homeostasis by accumulated studies. Here,
      we speculate that SIRT1 might mediate the effect of the GLP-1 receptor agonist
      exenatide (exendin-4) on ameliorating hepatic steatosis. After 8 weeks of
      exenatide treatment in male SIRT1(+/-) mice challenged with a high-fat diet and
      their wild-type (WT) littermates, we found that lipid deposition and inflammation
      in the liver, which were improved dramatically in the WT group, diminished in
      SIRT1(+/-) mice. In addition, the protein expression of SIRT1 and phosphorylated
      AMPK was upregulated, whereas lipogenic-related protein, including SREBP-1c and
      PNPLA3, was downregulated in the WT group after exenatide treatment. However,
      none of these changes were observed in SIRT1(+/-) mice. In HepG2 cells, exendin-4
      reversed lipid deposition induced by palmitate was hampered when SIRT1 was
      silenced by SIRT1 RNA interference. Our data demonstrate that SIRT1 mediates the
      effect of exenatide on ameliorating hepatic steatosis, suggesting the GLP-1
      receptor agonist could serve as a potential drug for nonalcoholic fatty liver
      disease (NAFLD), especially in type 2 diabetes combined with NAFLD, and SIRT1
      could be a therapeutic target of NAFLD. 

PMID- 24947349
TI  - Changes in glucose and fat metabolism in response to the administration of a
      hepato-preferential insulin analog.
AB  - Endogenous insulin secretion exposes the liver to three times higher insulin
      concentrations than the rest of the body. Because subcutaneous insulin delivery
      eliminates this gradient and is associated with metabolic abnormalities,
      functionally restoring the physiologic gradient may provide therapeutic benefits.
      The effects of recombinant human insulin (HI) delivered intraportally or
      peripherally were compared with an acylated insulin model compound (insulin-327)
      in dogs. During somatostatin and basal portal vein glucagon infusion, insulin was
      infused portally (PoHI; 1.8 pmol/kg/min; n = 7) or peripherally (PeHI; 1.8
      pmol/kg/min; n = 8) and insulin-327 (Pe327; 7.2 pmol/kg/min; n = 5) was infused
      peripherally. Euglycemia was maintained by glucose infusion. While the effects on
      liver glucose metabolism were greatest in the PoHI and Pe327 groups, nonhepatic
      glucose uptake increased most in the PeHI group. Suppression of lipolysis was
      greater during PeHI than PoHI and was delayed in Pe327 infusion. Thus small
      increments in portal vein insulin have major consequences on the liver, with
      little effect on nonhepatic glucose metabolism, whereas insulin delivered
      peripherally cannot act on the liver without also affecting nonhepatic tissues.
      Pe327 functionally restored the physiologic portal-arterial gradient and thereby
      produced hepato-preferential effects. 

PMID- 24947351
TI  - Fractalkine (CX3CL1) is involved in the early activation of hypothalamic
      inflammation in experimental obesity.
AB  - Hypothalamic inflammation is a common feature of experimental obesity. Dietary
      fats are important triggers of this process, inducing the activation of toll-like
      receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells,
      which are the cellular components of the innate immune system in the brain, are
      expected to play a role in the early activation of diet-induced hypothalamic
      inflammation. Here, we use bone marrow transplants to generate mice chimeras that
      express a functional TLR4 in the entire body except in bone marrow-derived cells
      or only in bone marrow-derived cells. We show that a functional TLR4 in bone
      marrow-derived cells is required for the complete expression of the diet-induced
      obese phenotype and for the perpetuation of inflammation in the hypothalamus. In
      an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly
      induced in the neurons of the hypothalamus after the introduction of a high-fat
      diet. The inhibition of hypothalamic fractalkine reduces diet-induced
      hypothalamic inflammation and the recruitment of bone marrow-derived monocytic
      cells to the hypothalamus; in addition, this inhibition reduces obesity and
      protects against diet-induced glucose intolerance. Thus, fractalkine is an
      important player in the early induction of diet-induced hypothalamic
      inflammation, and its inhibition impairs the induction of the obese and glucose
      intolerance phenotypes. 

PMID- 24947353
TI  - White matter integrity disruptions associated with cognitive impairments in type
      2 diabetic patients.
AB  - Type 2 diabetes mellitus (T2DM) is associated with a twofold increased risk of
      dementia and can affect many cognitive abilities, but its underlying cause is
      still unclear. In this study, we used a combination of a battery of
      neuropsychological tests and diffusion tensor imaging (DTI) to explore how T2DM
      affects white matter (WM) integrity and cognition in 38 T2DM patients and 34 age
      , sex-, and education-matched normal control subjects. A battery of
      neuropsychological tests was used to assess a wide range of cognitive functions.
      Tract-based spatial statistics combined with region of interest-wise (ROI-wise)
      analysis of mean values of DTI metrics in ROIs was used to compare group
      differences of DTI metrics on WM skeletons to identify severely disrupted WM
      tracts in T2DM. We found that T2DM patients showed 1) various cognitive
      impairments, including executive function, spatial processing, attention, and
      working memory deficits; 2) widespread WM disruptions, especially in the whole
      corpus callosum, the left anterior limb of the internal capsule (ALIC.L), and
      external capsule (EC); and 3) a positive correlation between executive function
      and WM integrity in the ALIC.L and the left EC. In conclusion, T2DM patients show
      various cognitive impairments and widespread WM integrity disruptions, which we
      attribute to demyelination. Moreover, executive dysfunction closely correlates
      with WM abnormalities. 

PMID- 24947352
TI  - Distinct developmental profile of lower-body adipose tissue defines resistance
      against obesity-associated metabolic complications.
AB  - Upper- and lower-body fat depots exhibit opposing associations with obesity
      related metabolic disease. We defined the relationship between DEXA-quantified
      fat depots and diabetes/cardiovascular risk factors in a healthy population-based
      cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance
      after total fat mass adjustment, whereas the opposite was seen for abdominal fat.
      Paired transcriptomic analysis of gluteal subcutaneous adipose tissue (GSAT) and
      abdominal subcutaneous adipose tissue (ASAT) was performed across the BMI
      spectrum (n = 49; 21.4-45.5 kg/m(2)). In both depots, energy-generating metabolic
      genes were negatively associated and inflammatory genes were positively
      associated with obesity. However, associations were significantly weaker in GSAT.
      At the systemic level, arteriovenous release of the proinflammatory cytokine
      interleukin-6 (n = 34) was lower from GSAT than ASAT. Isolated preadipocytes
      retained a depot-specific transcriptional "memory" of embryonic developmental
      genes and exhibited differential promoter DNA methylation of selected genes
      (HOTAIR, TBX5) between GSAT and ASAT. Short hairpin RNA-mediated silencing
      identified TBX5 as a regulator of preadipocyte proliferation and adipogenic
      differentiation in ASAT. In conclusion, intrinsic differences in the expression
      of developmental genes in regional adipocytes provide a mechanistic basis for
      diversity in adipose tissue (AT) function. The less inflammatory nature of lower
      body AT offers insight into the opposing metabolic disease risk associations
      between upper- and lower-body obesity. 

PMID- 24947354
TI  - Neuroretinal dysfunction with intact blood-retinal barrier and absent
      vasculopathy in type 1 diabetes.
AB  - It is unknown whether independent neural damage may occur in the pre-/absent
      vascular diabetic retinopathy (DR). To exclude vasculopathy, it is important to
      measure the integrity of the blood-retinal barrier (BRB). This cross-sectional
      study addressed this problem in type 1 diabetic patients with normal ocular
      fundus and absent breakdown of the BRB (confirmed with vitreous fluorometry).
      These were compared with a group with disrupted BRB (with normal fundus or
      initial DR) and normal controls. Multifocal electroretinography and
      chromatic/achromatic contrast sensitivity were measured in these 42 patients with
      preserved visual acuity. Amplitudes of neurophysiological responses (multifocal
      electroretinogram) were decreased in all eccentricity rings in both clinical
      groups, when compared with controls, with sensitivity >78% for a specificity
      level of 90%. Implicit time changes were also found in the absence of initial DR.
      Impaired contrast sensitivity along chromatic axes was also observed, and
      achromatic thresholds were also different between controls and both clinical
      groups. The pattern of changes in the group without baseline BRB permeability
      alterations, as probed by psychophysical and electrophysiological measurements,
      does thereby confirm independent damage mechanisms. We conclude that retinal
      neuronal changes can be diagnosed in type 1 diabetes, independently of the
      breakdown of the BRB and onset of vasculopathy. 

PMID- 24947355
TI  - Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is
      required for insulin signaling and is implicated in hepatic insulin resistance.
AB  - Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are
      functional domains between both organelles involved in Ca(2+) exchange, through
      the voltage-dependent anion channel (VDAC)-1/glucose-regulated protein 75
      (Grp75)/inositol 1,4,5-triphosphate receptor (IP3R)-1 complex, and regulating
      energy metabolism. Whereas mitochondrial dysfunction, ER stress, and altered
      Ca(2+) homeostasis are associated with altered insulin signaling, the implication
      of MAM dysfunctions in insulin resistance is unknown. Here we validated an
      approach based on in situ proximity ligation assay to detect and quantify
      VDAC1/IP3R1 and Grp75/IP3R1 interactions at the MAM interface. We demonstrated
      that MAM integrity is required for insulin signaling and that induction of MAM
      prevented palmitate-induced alterations of insulin signaling in HuH7 cells.
      Disruption of MAM integrity by genetic or pharmacological inhibition of the
      mitochondrial MAM protein, cyclophilin D (CypD), altered insulin signaling in
      mouse and human primary hepatocytes and treatment of CypD knockout mice with
      metformin improved both insulin sensitivity and MAM integrity. Furthermore, ER
      mitochondria interactions are altered in liver of both ob/ob and diet-induced
      insulin-resistant mice and improved by rosiglitazone treatment in the latter.
      Finally, increasing organelle contacts by overexpressing CypD enhanced insulin
      action in primary hepatocytes of diabetic mice. Collectively, our data reveal a
      new role of MAM integrity in hepatic insulin action and resistance, providing a
      novel target for the modulation of insulin action. 

PMID- 24947356
TI  - GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner,
      leading to hyperinsulinemia and blood glucose lowering.
AB  - Hypoglycemia and hyperglycemia are both predictors for adverse outcome in
      critically ill patients. Hyperinsulinemia is induced by inflammatory stimuli as a
      relevant mechanism for glucose lowering in the critically ill. The incretine
      hormone GLP-1 was currently found to be induced by endotoxin, leading to insulin
      secretion and glucose lowering under inflammatory conditions in mice. Here, we
      describe GLP-1 secretion to be increased by a variety of inflammatory stimuli,
      including endotoxin, interleukin-1beta (IL-1beta), and IL-6. Although abrogation
      of IL-1 signaling proved insufficient to prevent endotoxin-dependent GLP-1
      induction, this was abolished in the absence of IL-6 in respective knockout
      animals. Hence, we found endotoxin-dependent GLP-1 secretion to be mediated by an
      inflammatory cascade, with IL-6 being necessary and sufficient for GLP-1
      induction. Functionally, augmentation of the GLP-1 system by pharmacological
      inhibition of DPP-4 caused hyperinsulinemia, suppression of glucagon release, and
      glucose lowering under endotoxic conditions, whereas inhibition of the GLP-1
      receptor led to the opposite effect. Furthermore, total GLP-1 plasma levels were
      profoundly increased in 155 critically ill patients presenting to the intensive
      care unit (ICU) in comparison with 134 healthy control subjects. In the ICU
      cohort, GLP-1 plasma levels correlated with markers of inflammation and disease
      severity. Consequently, GLP-1 provides a novel link between the immune system and
      the gut with strong relevance for metabolic regulation in context of
      inflammation. 

PMID- 24947357
TI  - IRS1 G972R missense polymorphism is associated with failure to oral antidiabetes
      drugs in white patients with type 2 diabetes from Italy.
AB  - This study tried to replicate in a large sample of white patients with type 2
      diabetes (T2D) from Italy a previously reported association of the IRS1 G972R
      polymorphism with failure to oral antidiabetes drugs (OAD). A total of 2,409
      patients from four independent studies were investigated. Case subjects (n =
      1,193) were patients in whom, because of uncontrolled diabetes (i.e., HbA1c >8%),
      insulin therapy had been added either on, or instead of, maximal or near-maximal
      doses of OAD, mostly metformin and sulfonylureas; control subjects (n = 1,216)
      were patients with HbA1c <8% in the absence of insulin therapy. The IRS1 G972R
      polymorphism was typed by TaqMan allele discrimination. In all samples,
      individuals carrying the IRS1 R972 risk variant tended to be more frequent among
      case than control subjects, though reaching statistical significance only in one
      case. As no IRS1 G972R-by-study sample interaction was observed, data from the
      four samples were analyzed together; a significant association was observed
      (allelic odds ratio [OR] 1.30, 95% CI 1.03-1.63). When our present data were meta
      analyzed with those obtained in a previous study, an overall R972 allelic OR of
      1.37 (1.12-1.69) was observed. This study confirms in a large and ethnically
      homogeneous sample that IRS1 G972R polymorphism is associated with failure to OAD
      among patients with T2D. 

PMID- 24947358
TI  - Peroxiredoxin 6, a novel player in the pathogenesis of diabetes.
AB  - Enhanced oxidative stress contributes to the pathogenesis of diabetes and its
      complications. Peroxiredoxin 6 (PRDX6) is a key regulator of cellular redox
      balance, with the peculiar ability to neutralize peroxides, peroxynitrite, and
      phospholipid hydroperoxides. In the current study, we aimed to define the role of
      PRDX6 in the pathophysiology of type 2 diabetes (T2D) using PRDX6 knockout (-/-)
      mice. Glucose and insulin responses were evaluated respectively by
      intraperitoneal glucose and insulin tolerance tests. Peripheral insulin
      sensitivity was analyzed by euglycemic-hyperinsulinemic clamp, and molecular
      tools were used to investigate insulin signaling. Moreover, inflammatory and
      lipid parameters were evaluated. We demonstrated that PRDX6(-/-) mice developed a
      phenotype similar to early-stage T2D caused by both reduced glucose-dependent
      insulin secretion and increased insulin resistance. Impaired insulin signaling
      was present in PRDX6(-/-) mice, leading to reduction of muscle glucose uptake.
      Morphological and ultrastructural changes were observed in islets of Langerhans
      and livers of mutant animals, as well as altered plasma lipid profiles and
      inflammatory parameters. In conclusion, we demonstrated that PRDX6 is a key
      mediator of overt hyperglycemia in T2D glucose metabolism, opening new
      perspectives for targeted therapeutic strategies in diabetes care. 

PMID- 24947359
TI  - Macrophage HIF-2alpha ameliorates adipose tissue inflammation and insulin
      resistance in obesity.
AB  - In obesity, adipose tissue macrophages (ATMs) play a key role in mediating
      proinflammatory responses in the adipose tissue, which are associated with
      obesity-related metabolic complications. Recently, adipose tissue hypoxia has
      been implicated in the regulation of ATMs in obesity. However, the role of
      hypoxia-inducible factor (HIF)-2alpha, one of the major transcription factors
      induced by hypoxia, has not been fully elucidated in ATMs. In this study, we
      demonstrate that elevation of macrophage HIF-2alpha would attenuate adipose
      tissue inflammation and improve insulin resistance in obesity. In macrophages,
      overexpression of HIF-2alpha decreased nitric oxide production and suppressed
      expression of proinflammatory cytokines through induction of arginase 1. HIF
      2alpha-overexpressing macrophages alleviated proinflammatory responses and
      improved insulin resistance in adipocytes. In contrast, knockdown of macrophage
      HIF-2alpha augmented palmitate-induced proinflammatory gene expression in
      adipocytes. Furthermore, compared with wild-type mice, Hif-2alpha heterozygous
      null mice aggravated insulin resistance and adipose tissue inflammation with more
      M1-like ATMs upon high-fat diet (HFD). Moreover, glucose intolerance in HFD-fed
      Hif-2alpha heterozygous-null mice was relieved by macrophage depletion with
      clodronate treatment, implying that increase of proinflammatory ATMs is
      responsible for insulin resistance by haplodeficiency of Hif-2alpha upon HFD.
      Taken together, these data suggest that macrophage HIF-2alpha would counteract
      the proinflammatory responses to relieve obesity-induced insulin resistance in
      adipose tissue. 

PMID- 24947360
TI  - beta-cell function, incretin effect, and incretin hormones in obese youth along
      the span of glucose tolerance from normal to prediabetes to type 2 diabetes.
AB  - Using the hyperglycemic and euglycemic clamp, we demonstrated impaired beta-cell
      function in obese youth with increasing dysglycemia. Herein we describe oral
      glucose tolerance test (OGTT)-modeled beta-cell function and incretin effect in
      obese adolescents spanning the range of glucose tolerance. beta-Cell function
      parameters were derived from established mathematical models yielding beta-cell
      glucose sensitivity (betaCGS), rate sensitivity, and insulin sensitivity in 255
      obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired
      glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect
      was calculated as the ratio of the OGTT-betaCGS to the 2-h hyperglycemic clamp
      betaCGS. Incretin and glucagon concentrations were measured during the OGTT.
      Compared with NGT, betaCGS was 30 and 65% lower in youth with IGT and T2D,
      respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32
      and 38% reduced incretin effect compared with NGT in the face of similar changes
      in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to
      oral glucose. We conclude that glucose sensitivity deteriorates progressively in
      obese youth across the spectrum of glucose tolerance in association with
      impairment in incretin effect without reduction in GLP-1 or GIP, similar to that
      seen in adult dysglycemia. 

PMID- 24947361
TI  - Prohibitin overexpression in adipocytes induces mitochondrial biogenesis, leads
      to obesity development, and affects glucose homeostasis in a sex-specific manner.
AB  - Adipocytes are the primary cells in the body that store excess energy as
      triglycerides. To perform this specialized function, adipocytes rely on their
      mitochondria; however, the role of adipocyte mitochondria in the regulation of
      adipose tissue homeostasis and its impact on metabolic regulation is not
      understood. We developed a transgenic mouse model, Mito-Ob, overexpressing
      prohibitin (PHB) in adipocytes. Mito-Ob mice developed obesity due to
      upregulation of mitochondrial biogenesis in adipocytes. Of note, Mito-Ob female
      mice developed more visceral fat than male mice. However, female mice exhibited
      no change in glucose homeostasis and had normal insulin and high adiponectin
      levels, whereas male mice had impaired glucose homeostasis, compromised brown
      adipose tissue structure, and high insulin and low adiponectin levels.
      Mechanistically, we found that PHB overexpression enhances the cross talk between
      the mitochondria and the nucleus and facilitates mitochondrial biogenesis. The
      data suggest a critical role of PHB and adipocyte mitochondria in adipose tissue
      homeostasis and reveal sex differences in the effect of PHB-induced adipocyte
      mitochondrial remodeling on whole-body metabolism. Targeting adipocyte
      mitochondria may provide new therapeutic opportunities for the treatment of
      obesity, a major risk factor for type 2 diabetes. 

PMID- 24947362
TI  - Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset
      type 1 diabetes: a multicenter analysis.
AB  - Type 1 diabetes (T1D) is one of the major autoimmune diseases affecting children
      and young adults worldwide. To date, the different immunotherapies tested have
      achieved insulin independence in <5% of treated individuals. Recently, a novel
      hematopoietic stem cell (HSC)-based strategy has been tested in individuals with
      new-onset T1D. The aim of this study was to determine the effects of autologous
      nonmyeloablative HSC transplantation in 65 individuals with new-onset T1D who
      were enrolled in two Chinese centers and one Polish center, pooled, and followed
      up for 48 months. A total of 59% of individuals with T1D achieved insulin
      independence within the first 6 months after receiving conditioning
      immunosuppression therapy (with antithymocyte globulin and cyclophosphamide) and
      a single infusion of autologous HSCs, and 32% remained insulin independent at the
      last time point of their follow-up. All treated subjects showed a decrease in
      HbA1c levels and an increase in C-peptide levels compared with pretreatment.
      Despite a complete immune system recovery (i.e., leukocyte count) after
      treatment, 52% of treated individuals experienced adverse effects. Our study
      suggests the following: 1) that remission of T1D is possible by combining HSC
      transplantation and immunosuppression; 2) that autologous nonmyeloablative HSC
      transplantation represents an effective treatment for selected individuals with
      T1D; and 3) that safer HSC-based therapeutic options are required. 

PMID- 24947363
TI  - Identification of novel autoantibodies in type 1 diabetic patients using a high
      density protein microarray.
AB  - Autoantibodies can facilitate diagnostic and therapeutic means for type 1
      diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM
      patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects
      with normal glucose tolerance (NGT) by using protein microarrays containing 9,480
      proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected
      from microarrays followed by immunofluorescence staining of pancreas. We then
      tested the validity of the candidates by ELISA in two independent test cohorts:
      1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in
      adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with
      T1DM and 34 healthy children. Concentrations of these autoantibodies were
      significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01),
      which was also confirmed in the test cohort of children (P < 0.05). Prevalence of
      anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively.
      Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti
      EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with
      fulminant T1DM but not LADA. Our approach identified autoantibodies that can
      provide a new dimension of information indicative of T1DM independent of GADA and
      new insights into diagnosis and classification of T1DM.

PMID- 24947365
TI  - Cyclin D1 represses gluconeogenesis via inhibition of the transcriptional
      coactivator PGC1alpha.
AB  - Hepatic gluconeogenesis is crucial to maintain normal blood glucose during
      periods of nutrient deprivation. Gluconeogenesis is controlled at multiple levels
      by a variety of signal transduction and transcriptional pathways. However,
      dysregulation of these pathways leads to hyperglycemia and type 2 diabetes. While
      the effects of various signaling pathways on gluconeogenesis are well
      established, the downstream signaling events repressing gluconeogenic gene
      expression are not as well understood. The cell-cycle regulator cyclin D1 is
      expressed in the liver, despite the liver being a quiescent tissue. The most well
      studied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4),
      promoting progression of the cell cycle. We show here a novel role for cyclin D1
      as a regulator of gluconeogenic and oxidative phosphorylation (OxPhos) gene
      expression. In mice, fasting decreases liver cyclin D1 expression, while
      refeeding induces cyclin D1 expression. Inhibition of CDK4 enhances the
      gluconeogenic gene expression, whereas cyclin D1-mediated activation of CDK4
      represses the gluconeogenic gene-expression program in vitro and in vivo.
      Importantly, we show that cyclin D1 represses gluconeogenesis and OxPhos in part
      via inhibition of peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC1alpha) activity in a CDK4-dependent manner. Indeed, we demonstrate
      that PGC1alpha is novel cyclin D1/CDK4 substrate. These studies reveal a novel
      role for cyclin D1 on metabolism via PGC1alpha and reveal a potential link
      between cell-cycle regulation and metabolic control of glucose homeostasis. 

PMID- 24947364
TI  - Common genetic variants highlight the role of insulin resistance and body fat
      distribution in type 2 diabetes, independent of obesity.
AB  - We aimed to validate genetic variants as instruments for insulin resistance and
      secretion, to characterize their association with intermediate phenotypes, and to
      investigate their role in type 2 diabetes (T2D) risk among normal-weight,
      overweight, and obese individuals. We investigated the association of genetic
      scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test
      based measures of insulin resistance and secretion and a range of metabolic
      measures in up to 18,565 individuals. We also studied their association with T2D
      risk among normal-weight, overweight, and obese individuals in up to 8,124
      incident T2D cases. The insulin resistance score was associated with lower
      insulin sensitivity measured by M/I value (beta in SDs per allele [95% CI], -0.03
      [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [
      0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05, -0.02; P = 1.4 *
      10(-6)) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and
      gamma-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion
      score had a stronger association with T2D in leaner individuals (Pinteraction =
      0.001), we saw no difference in the association of the insulin resistance score
      with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin
      resistance is often considered secondary to obesity, the association of the
      insulin resistance score with lower BMI and adiposity and with incident T2D even
      among individuals of normal weight highlights the role of insulin resistance and
      ectopic fat distribution in T2D, independently of body size. 

PMID- 24947366
TI  - Heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion, but not
      insulin action, in high-fat-fed mice.
AB  - Elevated reactive oxygen species (ROS) are linked to insulin resistance and islet
      dysfunction. Manganese superoxide dismutase (SOD2) is a primary defense against
      mitochondrial oxidative stress. To test the hypothesis that heterozygous SOD2
      deletion impairs glucose-stimulated insulin secretion (GSIS) and insulin action,
      wild-type (sod2(+/+)) and heterozygous knockout mice (sod2(+/-)) were fed a chow
      or high-fat (HF) diet, which accelerates ROS production. Hyperglycemic (HG) and
      hyperinsulinemic-euglycemic (HI) clamps were performed to assess GSIS and insulin
      action in vivo. GSIS during HG clamps was equal in chow-fed sod2(+/-) and
      sod2(+/+) but was markedly decreased in HF-fed sod2(+/-). Remarkably, this
      impairment was not paralleled by reduced HG glucose infusion rate (GIR).
      Decreased GSIS in HF-fed sod2(+/-) was associated with increased ROS, such as
      superoxide ion. Surprisingly, insulin action determined by HI clamps did not
      differ between sod2(+/-) and sod2(+/+) of either diet. Since insulin action was
      unaffected, we hypothesized that the unchanged HG GIR in HF-fed sod2(+/-) was due
      to increased glucose effectiveness. Increased GLUT-1, hexokinase II, and phospho
      AMPK protein in muscle of HF-fed sod2(+/-) support this hypothesis. We conclude
      that heterozygous SOD2 deletion in mice, a model that mimics SOD2 changes
      observed in diabetic humans, impairs GSIS in HF-fed mice without affecting
      insulin action. 

PMID- 24947367
TI  - Increased immune cell infiltration of the exocrine pancreas: a possible
      contribution to the pathogenesis of type 1 diabetes.
AB  - Type 1 diabetes (T1D) results from a complex interplay between genetic
      susceptibility and environmental factors that have been implicated in the
      pathogenesis of disease both as triggers and potentiators of beta-cell
      destruction. CD8 T cells are the main cell type found in human islets, and they
      have been shown in vitro to be capable of killing beta-cells overexpressing MHC
      class I. In this study, we report that CD8 T cells infiltrate the exocrine
      pancreas of diabetic subjects in high numbers and not only endocrine areas. T1D
      subjects present significantly higher CD8 T cell density in the exocrine tissue
      without the presence of prominent insulitis. Even T1D donors without remaining
      insulin-containing islets and long disease duration show elevated levels of CD8 T
      cells in the exocrine compartment. In addition, higher numbers of CD4(+) and
      CD11c(+) cells were found in the exocrine tissue. Preliminary data in type 2
      diabetic (T2D) subjects indicate that overall, there might be a spontaneous
      inflammatory infiltration of the exocrine tissue, common to both T1D and T2D
      subjects. Our study provides the first information on the precise tissue
      distribution of CD8 T cells in pancreata from T1D, T2D, autoantibody-positive,
      and healthy control subjects. 

PMID- 24947369
TI  - Layer anti-ferromagnetism on bilayer honeycomb lattice.
AB  - Bilayer honeycomb lattice, with inter-layer tunneling energy, has a parabolic
      dispersion relation, and the inter-layer hopping can cause the charge imbalance
      between two sublattices. Here, we investigate the metal-insulator and magnetic
      phase transitions on the strongly correlated bilayer honeycomb lattice by
      cellular dynamical mean-field theory combined with continuous time quantum Monte
      Carlo method. The procedures of magnetic spontaneous symmetry breaking on dimer
      and non-dimer sites are different, causing a novel phase transition between
      normal anti-ferromagnet and layer anti-ferromagnet. The whole phase diagrams
      about the magnetism, temperature, interaction and inter-layer hopping are
      obtained. Finally, we propose an experimental protocol to observe these phenomena
      in future optical lattice experiments. 

PMID- 24947370
TI  - EBUS in pulmonary sarcoidosis: What to expect?

PMID- 24947368
TI  - Mechanisms of increased in vivo insulin sensitivity by dietary methionine
      restriction in mice.
AB  - To understand the physiological significance of the reduction in fasting insulin
      produced by dietary methionine restriction (MR), hyperinsulinemic-euglycemic
      clamps were used to examine the effect of the diet on overall and tissue-specific
      insulin sensitivity in mice. The steady-state glucose infusion rate was threefold
      higher in the MR group and consistent with the 2.5- to threefold increase in 2
      deoxyglucose uptake in skeletal muscle, heart, and white adipose tissue. Dietary
      MR enhanced suppression of hepatic glucose production by insulin, enhanced
      insulin-dependent Akt phosphorylation in the liver, and increased hepatic
      expression and circulating fibroblast growth factor 21 (FGF-21) by fourfold.
      Limitation of media methionine recapitulated amplification of Akt phosphorylation
      by insulin in HepG2 cells but not in 3T3-L1 adipocytes or C2C12 myotubes.
      Amplification of insulin signaling in HepG2 cells by MR was associated with
      reduced glutathione, where it functions as a cofactor for phosphatase and tensin
      homolog. In contrast, FGF-21, but not restricting media methionine, enhanced
      insulin-dependent Akt phosphorylation in 3T3-L1 adipocytes. These findings
      provide a potential mechanism for the diet-induced increase in insulin
      sensitivity among tissues that involves a direct effect of methionine in liver
      and an indirect effect in adipose tissue through MR-dependent increases in
      hepatic transcription and release of FGF-21. 

PMID- 24947371
TI  - Pharmacological inhibitors of exocytosis and endocytosis: novel bullets for old
      targets.
AB  - Pharmacological inhibitors of vesicle trafficking possess great promise as
      valuable analytical tools for the study of a variety of biological processes and
      as potential therapeutic agents to fight microbial infections and cancer.
      However, many commonly used trafficking inhibitors are characterized by poor
      selectivity that diminishes their use in solving basic problems of cell biology
      or drug development. Recent high-throughput chemical screens intensified the
      search for novel modulators of vesicle trafficking, and successfully identified a
      number of small molecules that inhibit exocytosis and endocytosis in different
      types of mammalian cells. This chapter provides a systematic overview of recently
      discovered inhibitors of vesicle trafficking. It describes cellular effects and
      mechanisms of action of novel inhibitors of exocytosis and endocytosis.
      Furthermore, it pays special attention to the selectivity and possible off-target
      effects of these inhibitors. 

PMID- 24947372
TI  - Systematic analysis of endocytosis by cellular perturbations.
AB  - Endocytosis is an essential process of eukaryotic cells that facilitates numerous
      cellular and organismal functions. The formation of vesicles from the plasma
      membrane serves the internalization of ligands and receptors and leads to their
      degradation or recycling. A number of distinct mechanisms have been described
      over the years, several of which are only partially characterized in terms of
      mechanism and function. These are often referred to as novel endocytic pathways.
      The pathways differ in their mode of uptake and in their intracellular
      destination. Here, an overview of the set of cellular proteins that facilitate
      the different pathways is provided. Further, the approaches to distinguish
      between the pathways by different modes of perturbation are critically discussed,
      emphasizing the use of genetic tools such as dominant negative mutant proteins. 

PMID- 24947373
TI  - Real-time detection of SNARE complex assembly with FRET using the tetracysteine
      system.
AB  - Small tetracysteine insertions are more suitable for fluorescence resonance
      energy transfer (FRET) studies of protein folding and small complex assembly than
      bulky GFP-based fluorophores. Here, we describe a procedure for expression,
      purification, and fluorescent labeling of a FRET-based probe, called CSNAC that
      can track the conformational changes undergone by SNAP-25 as it folds in the
      exocytic complex. The fluorescent protein Cerulean was attached to the N-terminus
      and served as a FRET donor. The biarsenical dye FlAsH, served as a FRET acceptor,
      was bound to a short tetracysteine motif positioned in the linker domain of SNAP
      25. CSNAC can report real-time FRET changes when the Syntaxin soluble domain is
      added in vitro. 

PMID- 24947374
TI  - Profiling lysine ubiquitination by selective enrichment of ubiquitin remnant
      containing peptides.
AB  - Protein ubiquitination plays critical roles in many biological processes.
      However, functional studies of protein ubiquitination in eukaryotic cells are
      limited by the ability to identify protein ubiquitination sites. Unbiased high
      throughput screening methods are necessary to discover novel ubiquitination sites
      that play important roles in cellular regulation. Here, we describe an
      immunopurification approach that enriches ubiquitin remnant-containing peptides
      to facilitate downstream mass spectrometry (MS) identification of lysine
      ubiquitination sites. This approach can be utilized to identify ubiquitination
      sites from proteins in a complex mixture. 

PMID- 24947375
TI  - Secretion of circular proteins using sortase.
AB  - Circular proteins occur naturally and have been found in microorganisms, plants,
      and eukaryotes where they are commonly involved in host defense. Properties of
      circular proteins include enhanced resistance to exoproteases, increased
      thermostability, longer life spans, and increased activity. Using an enzymatic
      approach based on the bacterial sortase A (SrtA) transpeptidase, N- and C-termini
      of conventional linear proteins can be linked resulting in a circular protein.
      Circularization of bioengineered linear substrate proteins can indeed confer the
      desirable properties associated with circular proteins. Here, we describe how
      cells can be manipulated to secrete circularized proteins for substrates of
      choice via sortase-mediated circularization in the lumen of the endoplasmic
      reticulum. 

PMID- 24947376
TI  - Fractionation of subcellular membrane vesicles of epithelial and non-epithelial
      cells by OptiPrepTM density gradient ultracentrifugation.
AB  - Density gradient ultracentrifugation (DGUC) is widely used for physical isolation
      (enrichment rather than purification) of subcellular membrane vesicles. It has
      been a valuable tool to study specific subcellular localization and dynamic
      trafficking of proteins. While sucrose has been the main component of density
      gradients, several years ago, synthetic OptiPrepTM (iodixanol) began being used
      for separation of organelles due to its iso-osmotic property. Here, we describe a
      detailed protocol for density gradient fractionation of various mammalian
      subcellular vesicles, including endoplasmic reticulum (ER), Golgi apparatus,
      endosomes, and lipid rafts, as well as apical and basolateral membranes of
      polarized epithelial cells. 

PMID- 24947377
TI  - Combining pulsed SILAC labeling and click-chemistry for quantitative secretome
      analysis.
AB  - Secreted proteins, such as cytokines, chemokines, and hormones, exhibit central
      functions in intercellular communication, which is crucial to maintain
      homeostasis in every multicellular organism. A common approach to identify
      secreted proteins is by proteomic analysis of culture media after conditioning
      with a cell type of interest. This is preferably done in serum-free conditions to
      enable the detection of low-abundance secretory factors that would otherwise be
      masked by serum proteins. However, serum starvation introduces the risk of
      bringing cells in a stressed or perturbed state. A superior approach employs the
      enrichment of newly synthesized and secreted proteins from serum-containing
      growth medium. This is achieved by the combination of two metabolic labels:
      stable isotope-labeled amino acids for reliable quantification, and
      azidohomoalanine (AHA), an azide-bearing analogue of methionine, for the
      enrichment of newly synthesized and secreted proteins. This approach has been
      used to compare secretomes of multiple cell lines or to analyze proteins that are
      secreted upon a specific stimulation. Here we describe in detail the enrichment
      and quantification of newly synthesized and secreted proteins. 

PMID- 24947378
TI  - Probabilistic density maps to study the spatial organization of endocytosis.
AB  - Despite a large body of publications on endocytosis, only a few studies have
      focused on its spatial organization. To study how endocytosis is related to
      distinct cellular sites, we combine cell normalization by the "micropatterning
      technique" with the quantification of spatial organization by "probabilistic
      density mapping." Micropatterns of extracellular matrix proteins impose adhesive
      and non-adhesive areas to cultured cells and allow the control of adhesion
      geometry, shape, and cell organization. Probabilistic density maps provide a
      visual summary for 3D localization of the structures of interest and enable the
      extraction of robust statistics for quantification of cellular organization.
      Here, we provide a method to analyze and compare the spatial distribution of
      endocytosed ligands in micropatterned cells. This approach permits to establish
      the role of cellular adhesion on uptake mechanisms and to address the potential
      function of predefined sites of endocytosis. 

PMID- 24947379
TI  - Use of Kaede and Kikume green-red fusions for live cell imaging of G protein
      coupled receptors.
AB  - The fusion of fluorescent proteins to G protein-coupled receptors (GPCRs) is an
      important tool to study, e.g., trafficking and protein interactions of these
      important drug targets. In the past, the green fluorescent protein and its
      derivatives have been widely used as fluorescent tags. More recently, it was
      reported that photoconvertible fluorescent proteins (PCFPs) such as Kaede or
      Kikume green-red protein could also be used as fluorescent tags for GPCRs. These
      proteins have the obvious advantage that their fluorescence can be switched once
      the GPCR of interest has reached a specific subcellular compartment. Here, we
      summarize the recent progress for live cell imaging of GPCRs using these PCFPs
      for trafficking, biosynthesis, and protein/protein interaction studies. 

PMID- 24947380
TI  - HaloTag as a tool to investigate peroxisome dynamics in cultured mammalian cells.
AB  - Peroxisomes are multifunctional organelles that can rapidly modulate their
      morphology, number, and function in response to changing environmental stimuli.
      Defects in any of these processes can lead to organelle dysfunction and have been
      associated with various inherited and age-related disorders. Progress in this
      field continues to be driven by advances in live-cell imaging techniques. This
      chapter provides detailed protocols for the use of HaloTag to fluorescently pulse
      label peroxisomes in cultured mammalian cells. In contrast to the use of
      classical fluorescent proteins, this technology allows researchers to optically
      distinguish pools of peroxisomal proteins that are synthesized at different time
      points. The protocols can be easily adapted to image the dynamics of other
      macromolecular protein assemblies in mammalian cells. 

PMID- 24947381
TI  - SNAP-tag to monitor trafficking of membrane proteins in polarized epithelial
      cells.
AB  - In order to understand the mechanisms through which apical and basolateral
      membrane proteins achieve their subcellular distributions in polarized epithelial
      cells, it is critical to develop techniques that permit the selective observation
      of newly synthesized populations of these proteins. The SNAP tag system permits
      the detection and visualization of distinct spatially and temporally defined
      cohorts of tagged proteins. Thus, this technique is especially well suited to
      studying the trafficking routes pursued by newly synthesized proteins. The SNAP
      tag can be applied in the setting of fixed or live cell fluorescence microscopic
      analysis and can also be used in the context of various biochemical approaches.
      Here, we describe the use of the SNAP tag in association with confocal microscopy
      and SDS-PAGE to follow the biosynthetic pool of a membrane protein as it exits
      from the trans-Golgi network and makes its way to the plasma membrane. 

PMID- 24947382
TI  - FlAsH-PALM: super-resolution pointillist imaging with FlAsH-tetracysteine
      labeling.
AB  - Super-resolution light microscopy including pointillist methods based on single
      molecule localization (e.g., PALM/STORM) allow to image protein structures much
      smaller than the diffraction limit (200-300 nm). However, commonly used labeling
      strategies such as antibodies or protein fusions have several important
      drawbacks, including the risk to alter the function or distribution of the imaged
      proteins. We recently demonstrated that pointillist imaging can be performed
      using the alternative labeling technique known as FlAsH, which better preserves
      protein function, is compatible with live cell imaging, and may help reach single
      nanometer resolution. We applied FlAsH-PALM to visualize HIV integrase in
      isolated virions or infected cells, allowing us to obtain sub-diffraction
      resolution images of this enzyme's spatial distribution and analyze HIV
      morphology without altering viral replication. The technique should also prove
      useful to image delicate proteins in intracellular vesicles and organelles at
      high resolution. Here, we present a detailed protocol in order to facilitate the
      application of FLAsH-PALM to other proteins and biological structures. 

PMID- 24947383
TI  - Analysis of protein dynamics with tandem fluorescent protein timers.
AB  - Fluorescent timers (FTs) are fluorescent proteins that change color with time.
      FTs can be used as tags to follow protein dynamics in living cells. Recently we
      described a novel class of FTs called tandem fluorescent protein timers (tFTs).
      Each tFT is a tandem fusion of two different conventional fluorescent proteins
      having distinct kinetics of fluorophore maturation. tFTs suitable for studying
      protein dynamics on different scales can be generated from a broad range of
      commonly used fluorescent proteins. Here we describe how to establish new tFTs
      and consider potential pitfalls. We detail a protocol for quantitative
      fluorescence microscopy imaging and analysis of intracellular protein dynamics
      with tFTs in the budding yeast Saccharomyces cerevisiae. 

PMID- 24947384
TI  - Synchronization of secretory cargos trafficking in populations of cells.
AB  - In mammalian cells, secretory proteins are transported to their destination
      compartment via the secretory pathway. Cargos start their journey in the
      endoplasmic reticulum and then reach the Golgi complex where they are processed
      and sorted to be delivered to their target intracellular compartment. To analyze
      and visualize this flow of proteins, one needs to synchronize their transport. We
      recently developed the retention using selective hooks (RUSH) system enabling
      simultaneous and synchronous release of secretory cargos from the endoplasmic
      reticulum in a population of cells. Here, we describe how to subclone the gene
      coding for a cargo of interest into a RUSH plasmid and to monitor its
      synchronized transport along the secretory pathway in fixed samples and in living
      cells. 

PMID- 24947385
TI  - Use of transmembrane FRET to investigate the internalization of glycosylated
      proteins.
AB  - The importance of glycans in various cellular events, especially intracellular
      and intercellular trafficking of proteins, has been reported in numerous studies.
      Here, we present a novel method to monitor endocytosis of proteins of interest
      bearing a specific glycan modification. Using a fluorescence resonance energy
      transfer technique, we investigated the role of glycan structure on the
      internalization of insulin-responsive glucose transporter GLUT4. We found that
      sialylated glycoforms of GFP-tagged GLUT4 appear to be internalized more slowly
      than non-sialylated GLUT4 upon insulin removal. This novel glycan imaging tool
      allows probing functional roles of specific glycan modifications in endocytosis
      of various proteins. 

PMID- 24947386
TI  - A method to rapidly induce organelle-specific molecular activities and membrane
      tethering.
AB  - In this chapter we describe a technique for rapid protein targeting to individual
      intracellular organelles. This method enables a real-time imaging-based study of
      cellular behavior in response to controlled induction of signaling events in a
      specifically targeted cellular compartment. We provide rationales and a step-by
      step protocol for probe design and imaging of protein targeting along with two
      different applications of this technique. One application involves organelle
      specific activation of small GTPases, while the other application involves
      membrane tethering of two different organelles. In the former case, we activate
      Rac1 and Ras at distinct intracellular locations in order to study
      compartmentalization of their signaling pathways, and in the latter example, we
      induce membrane tethering of the endoplasmic reticulum and mitochondria in order
      to study organelle-organelle communication. The described technique allows to
      rapidly perturb molecular activities and organelle-organelle communications at
      precise locations with specified timing and represents a powerful strategy to
      dissect spatiotemporally complex biological processes. 

PMID- 24947387
TI  - A novel pair of split venus fragments to detect protein-protein interactions by
      in vitro and in vivo bimolecular fluorescence complementation assays.
AB  - Protein-protein interactions are critical components of almost every cellular
      process. The bimolecular fluorescence complementation (BiFC) method has been used
      to detect protein-protein interactions in both living cells and cell-free
      systems. The BiFC method is based on the principle that a fluorescent protein is
      reassembled from its two complementary non-fluorescent fragments when an
      interaction occurs between two proteins, each one fused to each fragment. In vivo
      and in vitro BiFC assays, which use a new pair of split Venus fragments composed
      of VN210 (amino acids 1-210) and VC210 (amino acids 210-238), are useful tools to
      detect and quantify various protein-protein interactions (including the cofilin
      actin and Ras-Raf interactions) with high specificity and low background
      fluorescence. Moreover, these assays can be applied to screen small-molecule
      inhibitors of protein-protein interactions. 

PMID- 24947388
TI  - Real-time investigation of plasma membrane deformation and fusion pore expansion
      using polarized Total Internal Reflection Fluorescence Microscopy.
AB  - Polarized Total Internal Reflection Fluorescence Microscopy (pTIRFM) allows for
      real-time observation of plasma membrane deformations. The technique provides
      insights into the dynamics of biological processes requiring rapid and localized
      changes in membrane shape. Such processes include exocytosis, endocytosis,
      cytokinesis, and cell motility. In this chapter, we describe how to implement a
      polarization-based TIRF imaging system to monitor exocytosis in adrenal
      chromaffin cells. 

PMID- 24947389
TI  - Nanocones to study initial steps of endocytosis.
AB  - Vesicle endocytosis at the plasma membrane is associated with a precise temporal
      choreography in the recruitment of cytosolic proteins that sense, generate, or
      stabilize locally curved membrane regions. To dissect the role of membrane
      curvature sensing from other co-occurring events during the initial steps of
      endocytosis, we developed a method to artificially induce nanoscale deformations
      of the PM in living cells that is based on cone-shaped nanostructures (i.e.,
      Nanocones). When cultured on Nanocones, cells create stable inward plasma
      membrane deformations to which curvature-sensing proteins are recruited. Here, we
      provide a detailed protocol how to use Nanocones to study recruitment during the
      initial steps of endocytosis in cells by fluorescence and electron microscopy. 

PMID- 24947390
TI  - A novel permeabilization protocol to obtain intracellular 3D immunolabeling for
      electron tomography.
AB  - Electron tomography (ET) is a very important high-resolution tool for 3D imaging
      in cell biology. By combining the technique with immunolabeling, ET can provide
      essential insights into both cellular architecture and dynamics. We recently
      developed a protocol to achieve 3D immunolabeling of intracellular antigens
      without the need for uncontrolled permeabilization steps that cause random,
      extensive cell membrane disruption. Here we describe this novel method based on
      well-controlled permeabilization by targeted laser cell perforation. Mechanical
      permeabilization of the plasma membrane can be applied at specific sites without
      affecting other parts of the plasma membrane and intracellular membranes. Despite
      the relatively small opening created in the plasma membrane, the method allows
      specific 3D immunolocalization of cytoplasmic antigens in cultured cells by a pre
      embedment protocol. The approach is unique and leads to a superior
      ultrastructural preservation for transmission electron microscopy and electron
      tomography. 

PMID- 24947391
TI  - VIS2FIX: rapid chemical fixation of vitreous sections for immuno-electron
      microscopy.
AB  - Immuno-electron microscopy uniquely allows high-resolution localization of
      proteins in their cellular context. Usually, affinity labeling with an electron
      dense marker, e.g., small gold particles, is performed on sections of chemically
      fixed cells or tissues. In this chapter, we describe two novel protocols, the
      VIS2FIX methods, for chemical fixation of sections of cryo-immobilized biological
      samples. This method involves production of thin sections of high-pressure frozen
      cells that are statically adhered to a TEM grid. Subsequent steps involve
      chemical fixation of the samples by either the VIS2FIX(H) ("H" for "hydrated") or
      the VIS2FIX(FS) ("FS" for "freeze substitution") techniques. Following chemical
      fixation, the samples are ready for immunolabeling. The described methods are
      fast and efficient, yield excellent preservation of intracellular structures, and
      offer the possibility to maintain lipids in the sample.

PMID- 24947392
TI  - Chemical genomics: characterizing target pathways for bioactive compounds using
      the endomembrane trafficking network.
AB  - The plant endomembrane trafficking system is a highly complex set of processes.
      This complexity presents a challenge for its study. Classical plant genetics
      often struggles with loss-of-function lethality and gene redundancy. Chemical
      genomics allows overcoming many of these issues by using small molecules of
      natural or synthetic origin to inhibit specific trafficking proteins thereby
      affecting the processes in a tunable and reversible manner. Bioactive chemicals
      identified by high-throughput phenotype screens must be characterized in detail
      starting with understanding of the specific trafficking pathways affected. Here,
      we describe approaches to characterize bioactive compounds that perturb vesicle
      trafficking. This should equip researchers with practical knowledge on how to
      identify endomembrane-specific trafficking pathways that may be perturbed by
      specific compounds and will help to eventually identify molecular targets for
      these small molecules. 

PMID- 24947393
TI  - Application of RNAi technology and fluorescent protein markers to study membrane
      traffic in C. elegans.
AB  - RNA interference (RNAi) is a powerful tool to study the intracellular membrane
      transport and membrane organelle behavior in the nematode Caenorhabditis elegans.
      This model organism has gained popularity in the trafficking field because of its
      relative simplicity, yet being multicellular. C. elegans is fully sequenced and
      has an annotated genome, it is easy to maintain, and a growing number of
      transgenic strains bearing markers for different membrane compartments are
      available. C. elegans is particularly well suited for protein downregulation by
      RNAi because of the simple but efficient methods of dsRNA delivery. The
      phenomenon of systemic RNAi in the worm further facilitates this approach. In
      this chapter we describe methods and applications of RNAi in the field of
      membrane traffic. We summarize the fluorescent markers used as a readout for the
      effects of gene knockdown in different cells and tissues and give details for
      data acquisition and analysis. 

PMID- 24947394
TI  - Visualization of clathrin-mediated endocytosis in live Drosophila egg chambers.
AB  - In oviparous animals, clathrin-dependent endocytosis is often critical to
      stockpile a necessary supply of yolk within the maturing oocyte, which enables
      subsequent embryonic development. In the physically linked chains of maturing egg
      chambers within the Drosophila melanogaster ovary, a distinct, morphologically
      discernable subset undergoes a massive burst clathrin-mediated endocytosis to
      accumulate yolk in a process termed vitellogenesis. Here, we describe how to
      prepare isolated ovaries to follow endocytosis, and detail approaches to follow
      live uptake of soluble reporters into vitellogenic Drosophila egg chambers. 

PMID- 24947395
TI  - A novel extraction protocol to probe the role of cholesterol in synaptic vesicle
      recycling.
AB  - Cholesterol helps to stabilize membrane fluidity and many membrane proteins
      interact with cholesterol and are functionally clustered in cholesterol rich
      "rafts." Synaptic vesicle (SV) membranes are enriched in cholesterol in
      comparison to other organelles. Attempts to study the function of this high
      cholesterol content have been hampered by the inability to extract cholesterol
      from SVs in live presynaptic terminals. Here, we describe a method to extract
      vesicular cholesterol using a temperature-sensitive Drosophila dynamin mutant,
      shibire-ts1 (shi), to trap SVs on the plasma membrane. Trapped SVs are more
      accessible to cholesterol extraction by the cholesterol chelator, methyl-beta
      cyclodextrin (MbetaCD). This method can likely be extended to extract other
      lipids from SVs and could also be used to add lipids. We speculate that this
      method could be used on mammalian preparations in conjunction with dynamin
      inhibitors. 

PMID- 24947396
TI  - Microfluidic devices for imaging trafficking events in vivo using genetic model
      organisms.
AB  - Miniature devices are powerful new tools that can be used to address multiple
      questions in biology especially in investigating an individual cell or organism.
      The primary step forward has been the ease of soft lithography fabrication which
      has allowed researchers from different disciplines, with incomplete technical
      knowledge, to develop and use new devices for their own research problems. In
      this chapter, we describe a simple fabrication process that will allow
      investigators to make microfluidic devices for in vivo imaging studies using
      genetic model organisms such as C. elegans, Drosophila larvae, and zebrafish
      larvae. This microfluidic technology enables detailed studies on multiple
      cellular and subcellular phenomena including intracellular vesicle trafficking in
      living organisms over different developmental stages in an anesthetic free
      environment. 

PMID- 24947397
TI  - The "in situ" proximity ligation assay to probe protein-protein interactions in
      intact tissues.
AB  - The proximity ligation assay (PLA) is a sensitive and specific technique to
      visualize proteins, their posttranslational modifications and activation state as
      well as protein-protein interactions. The assay is based on the employment of
      proximity probes, composed by oligonucleotide-conjugated antibodies, to recognize
      a couple of specific targets. The binding of probes in close proximity allows for
      their hybridization by connector oligonucleotides, that can form a circular DNA
      strand. These DNA circles can then be amplified by polymerase chain reaction.
      Finally, the conjugation of fluorescence-labelled oligonucleotides with the
      amplification product allows for the localized detection of individual or
      interacting proteins in cells and tissues. Here, we describe the use of "in situ"
      PLA to visualize the localization of protein-protein interactions in intact
      tissues.

PMID- 24947398
TI  - Probing the role of the actin cytoskeleton during regulated exocytosis by
      intravital microscopy.
AB  - The actin cytoskeleton plays a fundamental role in controlling several steps
      during regulated exocytosis. Here, we describe a combination of procedures that
      are aimed at studying the dynamics and the mechanism of the actin cytoskeleton in
      the salivary glands of live rodents, a model for exocrine secretion. Our approach
      relies on intravital microscopy, an imaging technique that enables imaging
      biological events in live animals at a subcellular resolution, and it is
      complemented by the use of pharmacological agents and indirect immunofluorescence
      in the salivary tissue. 

PMID- 24947399
TI  - Measurement of dynamic F-actin changes during exocytosis.
AB  - Exocytosis requires the fusion of vesicle membrane to the cell membrane. It is
      tightly regulated and orchestrated in space and time by diverse cellular
      mechanisms. It has long been recognized that one of these mechanisms is an
      essential role played by the cytoskeleton. In particular, accumulating evidence
      shows that the F-actin network is engaged during the final stages of vesicle
      interactions with the cell membrane. Using a combination of methods it is now
      possible to gain insights into F-actin dynamics and reveal its role during
      exocytosis. Here, we describe the use of two-photon and confocal microscopy to
      visualize F-actin changes at the cell membrane during exocytosis. 

PMID- 24947401
TI  - Binocular correlation model of face preference: how good, how simple?

PMID- 24947400
TI  - A consensus statement regarding the utilization of BMP in spine surgery.
AB  - Recombinant human bone morphogenetic protein - 2 (rh-BMP-2) was first approved by
      the United States Food and Drug Administration (FDA) in 2002 for use in anterior
      lumbar interbody fusions. Since that time, it has been estimated that "off label"
      use accounts for 85 % of applications. Original, industry sponsored studies
      demonstrated superior fusion rates with decreased incidence of complications when
      compared with traditional iliac crest bone graft. These studies have been
      criticized for potential bias and newer research has detailed potential
      complications as well as alternative applications. Potential off label uses of
      rhBMP-2 include: anterior lumbar fusions, single level posterior lumbar fusions,
      multiple level posterior lumbar fusions, posterior cervical fusions, long
      deformity fusions, in the presence of vertebral osteomyelitis, and in patients
      with history of malignancy. A review of the literature related to rhBMP-2 was
      conducted to evaluate its use for the above-mentioned applications with a special
      focus on fusion rates, observed complications, and clinical or radiographic
      outcomes. 

PMID- 24947402
TI  - The effect of neighbourhood mortality shocks on fertility preferences: a spatial
      econometric approach.
AB  - According to the demographic transition theory, fertility rates fall in response
      to declines in child mortality rates. Although national statistics indicate that
      child mortality rates have been declining over time, Ghana's fertility rates
      appear to have stalled. This paper hypothesises that women's fertility behaviours
      may be more responsive to child mortality experiences at more localised levels.
      Using all rounds of the Ghana Demographic and Health Surveys (1988-2008) and
      employing a variety of spatial and empirical estimation techniques, results
      indicate that in addition to own-child mortality, neighbourhood child mortality
      shocks are also a determinant of women's fertility in Ghana. Women in
      neighbourhoods with large child mortality shocks may desire more children as an
      "insurance" against future losses, as a result of their increased perceptions of
      own-child mortality risks. 

PMID- 24947403
TI  - Graphene/Si-nanowire heterostructure molecular sensors.
AB  - Wafer-scale graphene/Si-nanowire (Si-NW) array heterostructures for molecular
      sensing have been fabricated by vertically contacting single-layer graphene with
      high-density Si NWs. Graphene is grown in large scale by chemical vapour
      deposition and Si NWs are vertically aligned by metal-assisted chemical etching
      of Si wafer. Graphene plays a key role in preventing tips of vertical Si NWs from
      being bundled, thereby making Si NWs stand on Si wafer separately from each other
      under graphene, a critical structural feature for the uniform Schottky-type
      junction between Si NWs and graphene. The molecular sensors respond very
      sensitively to gas molecules by showing 37 and 1280% resistance changes within
      3.5/0.15 and 12/0.15 s response/recovery times under O2 and H2 exposures in air,
      respectively, highest performances ever reported. These results together with the
      sensor responses in vacuum are discussed based on the surface-transfer doping
      mechanism.

PMID- 24947404
TI  - Altered decorin leads to disrupted endothelial cell function: a possible
      mechanism in the pathogenesis of fetal growth restriction?
AB  - OBJECTIVE: Fetal growth restriction (FGR) is a key cause of adverse pregnancy
      outcome where maternal and fetal factors are identified as contributing to this
      condition. Idiopathic FGR is associated with altered vascular endothelial cell
      functions. Decorin (DCN) has important roles in the regulation of endothelial
      cell functions in vascular environments. DCN expression is reduced in FGR. The
      objectives were to determine the functional consequences of reduced DCN in a
      human microvascular endothelial cell line model (HMVEC), and to determine
      downstream targets of DCN and their expression in primary placental microvascular
      endothelial cells (PLECs) from control and FGR-affected placentae. APPROACH:
      Short-interference RNA was used to reduce DCN expression in HMVECs and the effect
      on proliferation, angiogenesis and thrombin generation was determined. A Growth
      Factor PCR Array was used to identify downstream targets of DCN. The expression
      of target genes in control and FGR PLECs was performed. RESULTS: DCN reduction
      decreased proliferation and angiogenesis but increased thrombin generation with
      no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18
      and MSTN. Validation of target genes confirmed decreased expression of VEGFA,
      MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies.
      CONCLUSIONS: Reduction of DCN in vascular endothelial cells leads to disrupted
      cell functions. The targets of DCN include genes that play important roles in
      angiogenesis and cellular growth. Therefore, differential expression of these may
      contribute to the pathogenesis of FGR and disease states in other microvascular
      circulations.

PMID- 24947405
TI  - Histopathologic, biochemical and genotoxic investigations on chronic sodium
      nitrite toxicity in mice.
AB  - The aim of this study was to investigate the effects of long term Sodium nitrite
      (NaNO2) consumption. Swiss albino mice were given NaNO2 (0, 10 and 20 mg/kg/day)
      as mixed in feed for 8 months. At the end of treatments, animals were sacrificed
      and selected organs were processed for histopathologic, imunohistochemical,
      biochemical and genotoxic investigations. Mild to moderate degenerative changes
      were observed in liver, kidney, intestine, lung and spleen of NaNO2-given mice.
      Inducible nitric oxide synthase and nitrotyrosine activities increased in liver
      and kidney of NaNO2-given mice. Proliferating cell nuclear antigen activity
      increased in liver. Apoptotic cell death was observed in livers of the treatment
      groups. Liver malondialdehyde level was higher in the treatment groups while no
      change was seen in kidney. Nitric oxide levels in both liver and kidney of the
      treatment groups were lower than those of the control group. In genotoxic
      investigations, the number of chromosome and chromatid breaks, chromatid
      association, and polyploidy increased while mitotic index decreased in NaNO2
      given mice. The results showed that NaNO2 would cause histopathologic changes,
      nitrosative tissue damage, and lipid peroxidation in liver and kidney, as well as
      induce chromosomal aberrations even if it was given at low levels for long time.

PMID- 24947407
TI  - Mechanisms of hippocampal astrocytes mediation of spatial memory and theta rhythm
      by gliotransmitters and growth factors.
AB  - Our knowledge about encoding and maintenance of spatial memory emphasizes the
      integrated functional role of the grid cells and the place cells of the
      hippocampus in the generation of theta rhythm in spatial memory formation.
      However, the role of astrocytes in these processes is often underestimated in
      their contribution to the required structural and functional characteristics of
      hippocampal neural network operative in spatial memory. We show that hippocampal
      astrocytes, by the secretion of gliotransmitters, such as glutamate, d-serine,
      and ATP and growth factors such as BDNF and by the expression of receptors and
      channels such as those of TNFalpha and aquaporin, have several diverse fuctions
      in spatial memory. We specifically focus on the role of astrocytes on five phases
      of spatial memory: (1) theta rhythm generation, (2) theta phase precession, (3)
      formation of spatial memory by mapping data of entorhinal grid cells into the
      place cells, (4) storage of spatial information, and (5) maintenance of spatial
      memory. Finally, by reviewing the literature, we propose specific mechanisms
      mentioned in the form of a hypothesis suggesting that astrocytes are important in
      spatial memory formation.

PMID- 24947406
TI  - Early inflammatory response in epithelial ovarian tumor cyst fluids.
AB  - Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late
      stage diagnosis. The identification of biomarkers for this cancer could
      contribute to earlier diagnosis and increased survival rates. Given that chronic
      inflammation plays a central role in cancer initiation and progression, we
      selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian
      cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to
      the pathology and mined it for inflammatory biomarkers suitable for early
      detection of EOC. Immunoprecipitation and high-throughput sample fractionation
      were obtained by using tandem antibody libraries bead and mass spectrometry. Two
      proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL
      8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus
      benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated
      protein-alpha (GROalpha/CXCL1) was performed with ELISA in benign, borderline,
      and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was
      measured in serum from all patients and used in the algorithms performed. MCP-1,
      IL-8, and GROalpha are proinflammatory cytokines and promoters of tumor growth.
      From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROalpha were
      detected in the cyst fluids compared to the serum. Significant (P < 0.001)
      cytokine response was already established in borderline cyst fluids and stage I
      EOC. In serum a significant (P < 0.01) increase of IL-8 and GROalpha was found,
      but not until stage I and stage III EOC, respectively. These findings confirm
      that early events in tumorigenesis can be analyzed and detected in the tumor
      environment and we conclude that ovarian cyst fluid is a promising source in the
      search for new biomarkers for early ovarian tumors. 

PMID- 24947408
TI  - Hajek revisited: a histological examination of the quadrangular membrane.
AB  - OBJECTIVE: The predictability of laryngeal cancer spread is due in part to
      connective tissue membranes. These membranes function as barriers to cancer and
      divide the larynx into subunits. The field of laryngeal conservation surgery is
      based on these concepts. The quadrangular membrane plays an important role,
      hindering the lateral spread of cancer in the larynx. The composition of this
      membrane has not been well described in the literature. In this study, we examine
      basic characteristics of the quadrangular membrane using histological techniques.
      METHODS: Whole organ sections of the larynx were used. These sections were
      examined under a microscope with stains specific for collagen and elastin.
      RESULTS: Examination of the sections revealed that the quadrangular membrane is
      made up of closely woven undulating collagen and elastic fibers. CONCLUSION: The
      quadrangular membrane is a fibroelastic structure providing a barrier to cancer
      spread.

PMID- 24947409
TI  - The nitrate-sensing NasST system regulates nitrous oxide reductase and
      periplasmic nitrate reductase in Bradyrhizobium japonicum.
AB  - The soybean endosymbiont Bradyrhizobium japonicum is able to scavenge the
      greenhouse gas N2O through the N2O reductase (Nos). In previous research, N2O
      emission from soybean rhizosphere was mitigated by B. japonicum Nos(++) strains
      (mutants with increased Nos activity). Here, we report the mechanism underlying
      the Nos(++) phenotype. Comparative analysis of Nos(++) mutant genomes showed that
      mutation of bll4572 resulted in Nos(++) phenotype. bll4572 encodes NasS, the
      nitrate (NO3(-))-sensor of the two-component NasST regulatory system.
      Transcriptional analyses of nosZ (encoding Nos) and other genes from the
      denitrification process in nasS and nasST mutants showed that, in the absence of
      NO3(-) , nasS mutation induces nosZ and nap (periplasmic nitrate reductase) via
      nasT. NO3(-) addition dissociated the NasS-NasT complex in vitro, suggesting the
      release of the activator NasT. Disruption of nasT led to a marked decrease in
      nosZ and nap transcription in cells incubated in the presence of NO3(-). Thus,
      although NasST is known to regulate the NO3(-)-mediated response of NO3(-)
      assimilation genes in bacteria, our results show that NasST regulates the NO3(-) 
      mediated response of nosZ and napE genes, from the dissimilatory denitrification
      pathway, in B. japonicum.

PMID- 24947410
TI  - Complex karyotype in a case of cutaneous lymphangiosarcoma associated with
      chronic lymphedema of the lower limb.
AB  - Lymphangiosarcoma is a rare malignant neoplasm of endothelial cells. The term is
      used to describe an angiosarcoma associated with chronic lymphedema. The skin of
      the head and neck region is the most common site of origin. Rather few
      cytogenetic studies on lymphangiosarcoma are reported in the literature. We here
      describe a case of an 87-year-old woman, with a history of recurring lymphangitis
      and with an ulcerated nodular lesion of the leg. The histological diagnosis was a
      malignant neoplasm of vascular origin, with the morphological and
      immunohistochemical features of a lymphangiosarcoma. A series of antibodies
      (CD31, CD34, vimentin, podoplanin and HHV-8), conventional and molecular
      cytogenetic and Spectral Karyotyping (SKY-FISH) analyses were used to study this
      case. The immunohistochemical evaluation revealed that the neoplasm was positive
      for vimentin, CD31, CD34 and podoplanin and negative for HHV-8. The proliferation
      rate (Ki-67) was about 70%. Karyotype was defined using conventional cytogenetic
      and SKY-FISH. In addition, high-level of amplification was observed with MYC
      split signal probe. The morphological and immunohistochemical evaluations
      supported the diagnosis of lymphangiosarcoma. Moreover, the cytogenetic and
      molecular findings contributed towards accurately defining the karyotypic
      aberrations of this rare sarcoma. 

PMID- 24947411
TI  - A new pathological scoring method for adrenal injury in rats with severe acute
      pancreatitis.
AB  - These studies investigated the appearance and function of adrenal glands in rats
      with severe acute pancreatitis (SAP) and established a new histopathological
      score to evaluate adrenal histopathological changes. Severe acute pancreatitis
      relied on retrograde infusion of 5% sodium taurocholate into the bile-pancreatic
      duct. The damage of SAP was estimated by serum amylase, secretory phospholipase
      A2 and pancreatic histopathology. Light and electron microscopy of adrenal gland,
      and the levels of serum corticosterone were investigated. These results showed
      that the generally ascending trend of adrenal pathological score was inversely
      proportional to the generally descending trend of serum corticosterone levels,
      but parallel with the changes of pancreatic histopathology. Herein, the new
      adrenal histopathological score was effective in the evaluation of adrenal injury
      following SAP. It may indirectly reflect the variation of serum cortisol levels
      and the severity of pancreatitis to a certain extent. 

PMID- 24947412
TI  - Capecitabine induced colitis.
AB  - Capecitabine is an oral prodrug to 5-fluorouracil and is commonly used in the
      treatment of advanced breast, colon and stomach cancer. While gastrointestinal
      toxicity is common, enterocolitis and ischemic colitis are uncommon complications
      and the histologic features of capecitabine in the colonic mucosa have not been
      previously described. We present a case of colitis attributed to capecitabine
      toxicity in a 45-year-old man undergoing treatment of metastatic gastroesophageal
      adenocarcinoma. Possible pathophysiologic mechanisms of capecitabine toxicity are
      discussed and the histologic effects on the colon are described.

PMID- 24947413
TI  - Colon cancer bears overexpression of OTUB1.
AB  - OBJECTIVE: OTUB1 is a member of deubiquitinating enzymes; however, its expression
      and function in colon cancer are still unclear. The present study aimed at
      investigating the expression of OTUB1 in colon cancer and the relationship
      between the expression and some clinicopathologic parameters. METHODS:
      Immunohistochemistry and quantitative real-time PCR were carried out in selected
      colon cancer and normal mucosa tissues. RESULTS: The expression of OTUB1 protein
      in the colon cancer was significantly higher than normal mucosa, and the OTUB1
      mRNA in colon cancer was also 3.15-fold higher than the normal mucosa. The higher
      expression of OTUB1 in colon cancer was related with tumor size, differentiation
      and lymph node metastasis. CONCLUSIONS: OTUB1 may play an important role in colon
      cancer development and metastasis.

PMID- 24947414
TI  - Effect of BRCA1 immunohistochemical localizations on prognosis of patients with
      sporadic breast carcinomas.
AB  - Our purpose was to investigate the expression pattern of BRCA1 protein in
      sporadic breast carcinomas, as well as the clinicopathological and prognostic
      value of its subcellular localizations. Immunohistochemistry was performed on
      paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas
      to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67.
      BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells.
      Nuclear BRCA1 immunoreactivity showed no relation with the classic
      clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced
      expression of nuclear BRCA1 protein was found to exert an independent favorable
      impact on both the overall and relapse-free (RF) survival of the patients
      (p=0.019 and p=0.043, respectively). Cytoplasmic BRCA1 was associated with none
      of the classic histomorphological indices, except from the lymph node metastasis,
      with which its relation was found to be inverse (p=0.05), prolonging the RF
      survival of the patients (p=0.05). Our findings suggest that BRCA1 protein
      depicts different prognostic significance, according to its subcellular
      distribution. Nuclear detection of the protein was associated with a worse
      prognosis, while the cytoplasmic one was related to fewer recurrences as a result
      of fewer lymph node metastases. 

PMID- 24947415
TI  - Mitochondrial protection restores renal function in swine atherosclerotic
      renovascular disease.
AB  - AIMS: The mechanisms responsible for renal injury in atherosclerotic renovascular
      disease (ARVD) are incompletely understood, and few therapeutic options are
      available to reverse it. We hypothesized that chronic renal damage involves
      mitochondrial injury, and that mitochondrial protection would reduce renal
      fibrosis and dysfunction in ARVD pigs. METHODS AND RESULTS: Domestic pigs were
      studied after 10 weeks of ARVD or sham, treated for the last 4 weeks with daily
      subcutaneous injections (5 days/week) of vehicle or Bendavia (0.1 mg/kg), a
      tetrapeptide that preserves cardiolipin content in the mitochondrial inner
      membrane. Single-kidney haemodynamics and function were studied using fast
      computer tomography, oxygenation using blood oxygen level-dependent magnetic
      resonance imaging, microvascular architecture, oxidative stress, and fibrosis ex
      vivo. Cardiolipin content was assessed using mass spectrometry and staining.
      Renal endothelial function was studied in vivo and ex vivo. In addition, swine
      renal artery endothelial cells incubated with tert-butyl hydroperoxide were also
      treated with Bendavia. Stenotic-kidney renal blood flow (RBF) and glomerular
      filtration rate (GFR) decreased in ARVD + Vehicle compared with normal (318.8 +/-
      61.0 vs. 553.8 +/- 82.8 mL/min and 48.0 +/- 4.0 vs. 84.0 +/- 3.8 mL/min,
      respectively) associated with loss of cardiolipin, intra-renal microvascular
      rarefaction, and hypoxia. Bendavia restored cardiolipin content in ARVD and
      improved vascular density, oxygenation, RBF (535.1 +/- 24.9 mL/min), and GFR
      (86.6 +/- 11.2 mL/min). Oxidative stress and fibrosis were ameliorated, and
      renovascular endothelial function normalized both in vivo and in vitro.
      CONCLUSION: Preservation of mitochondrial cardiolipin attenuated swine stenotic
      kidney microvascular loss and injury, and improved renal oxygenation,
      haemodynamics, and function. These observations implicate mitochondrial damage in
      renal deterioration in chronic experimental ARVD, and position the mitochondria
      as a central therapeutic target.

PMID- 24947417
TI  - The effect of the nano-silica support on the catalytic reduction of water by
      gold, silver and platinum nanoparticles--nanocomposite reactivity.
AB  - Pt degrees -NPs, prepared by the reduction of Pt(IV) salts with borohydride, do
      not catalyse the reduction of water in the presence of the strongly-reducing
      C(CH3)2OH radicals. However, supporting the same metal nanoparticles (M degrees 
      NPs) with SiO2 alters the catalytic properties enabling the reaction. This effect
      depends both on the nature of M degrees  and concentration of the composite
      nanoparticles. At low nanocomposite concentration: for M = Au nearly no effect is
      observed; for M = Ag the support decreases the catalytic reduction of water and
      for M = Pt the support initiates the catalytic process. At high nanocomposite
      concentration: for M = Au the reactivity is considerably lower and for M = Ag or
      Pt no catalysis is observed. Furthermore, for M = Ag or Pt H2 reduces the
      C(CH3)2OH radicals. 

PMID- 24947416
TI  - Direct measurements of SR free Ca reveal the mechanism underlying the transient
      effects of RyR potentiation under physiological conditions.
AB  - AIMS: Most of the calcium that activates contraction is released from the
      sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). It is
      controversial whether activators of the RyR produce a maintained increase in the
      amplitude of the systolic Ca transient. We therefore aimed to examine the effects
      of activation of the RyR in large animals under conditions designed to be as
      physiological as possible while simultaneously measuring SR and cytoplasmic Ca.
      METHODS AND RESULTS: Experiments were performed on ventricular myocytes from
      canine and ovine hearts. Cytoplasmic Ca was measured with fluo-3 and SR Ca with
      mag-fura-2. Application of caffeine resulted in a brief increase in the amplitude
      of the systolic Ca transient accompanied by an increase of action potential
      duration. These effects disappeared with a rate constant of ~3 s(-1). Similar
      effects were seen in cells taken from sheep in which heart failure had been
      induced by rapid pacing. The decrease of Ca transient amplitude was accompanied
      by a decrease of SR Ca content. During this phase, the maximum (end-diastolic) SR
      Ca content fell while the minimum systolic increased. CONCLUSIONS: This study
      shows that, under conditions designed to be as physiological as possible,
      potentiation of RyR opening has no maintained effect on the systolic Ca
      transient. This result makes it unlikely that potentiation of the RyR has a
      maintained role in positive inotropy.

PMID- 24947418
TI  - Neurohistopathological findings at the electrode-tissue interface in long-term
      deep brain stimulation: systematic literature review, case report, and assessment
      of stimulation threshold safety.
AB  - OBJECTIVES: Despite the widespread use of deep brain stimulation (DBS) in the
      treatment of neurologic disorders for over a quarter of a century, there has not
      been a systematic review and analyses of cases in which long-term postmortem
      clinic-pathologic data have been collected demonstrating the effects of
      chronically implanted electrodes and electrical stimulation on human brain
      tissue. Our objective is to provide a comprehensive systematic review of the
      literature on clinicopathologic findings of DBS tissue-electrode interface (TEI)
      and to determine types and prevalences of neuropathological findings among
      electrode materials and stimulation parameters and to augment this with
      previously unpublished histopathological data, images, and analyses from a DBS
      case implanted for 12 years, providing the longest duration histopathological
      follow-up. MATERIALS AND METHODS: A Medline literature review identified DBS
      cases upon which postmortem clinicopathologic follow-up was performed with
      adequate characterization of TEI. Direct follow-up with authors augmented this
      with unpublished data and neuropathological details. RESULTS: We identified 40
      cases, mean age 59.1 +/- 13.0 (range: 21-88) years, involving 58 implanted DBS
      electrodes. The mean postmortem histopathological follow-up of the implanted DBS
      electrodes was 22.2 +/- 29.2 (range: 0.067-146) months, including our case with a
      12-year follow-up. The following histological changes were identified: fibrous
      sheaths (5-25 MUm thickness) surrounding the electrode (94%), fibrillary gliosis
      (73%), reactive astrocytes (78%), multinucleated giant cells (75%), mononuclear
      leukocytes (92%), and macrophages (91%). Microglial activation (60%), axonal
      spheroids (64%), and neuronal loss (60%) were less common and absent at 12-year
      follow-up in the index case. This is seventh case reporting T cell presence at
      the TEI. CONCLUSIONS: Neuropathological findings from published cases and our 12
      year follow-up index case confirm the long-term safety of neuromodulation and
      stimulation thresholds and demonstrate persistence of T cells and occasional
      subclinical focal tissue injury.

PMID- 24947419
TI  - The Asian diabetes phenotypes: challenges and opportunities.

PMID- 24947421
TI  - Diphtheria in Hyderabad: Do we need to do anything differently?

PMID- 24947420
TI  - Staff experiences within the implementation of computer-based nursing records in
      residential aged care facilities: a systematic review and synthesis of
      qualitative research.
AB  - BACKGROUND: Since the introduction of electronic nursing documentation systems,
      its implementation in recent years has increased rapidly in Germany. The
      objectives of such systems are to save time, to improve information handling and
      to improve quality. To integrate IT in the daily working processes, the employee
      is the pivotal element. Therefore it is important to understand nurses'
      experience with IT implementation. At present the literature shows a lack of
      understanding exploring staff experiences within the implementation process.
      METHODS: A systematic review and meta-ethnographic synthesis of primary studies
      using qualitative methods was conducted in PubMed, CINAHL, and Cochrane. It
      adheres to the principles of the PRISMA statement. The studies were original,
      peer-reviewed articles from 2000 to 2013, focusing on computer-based nursing
      documentation in Residential Aged Care Facilities. RESULTS: The use of IT
      requires a different form of information processing. Some experience this new
      form of information processing as a benefit while others do not. The latter find
      it more difficult to enter data and this result in poor clinical documentation.
      Improvement in the quality of residents' records leads to an overall improvement
      in the quality of care. However, if the quality of those records is poor, some
      residents do not receive the necessary care. Furthermore, the length of time
      necessary to complete the documentation is a prominent theme within that process.
      Those who are more efficient with the electronic documentation demonstrate
      improved time management. For those who are less efficient with electronic
      documentation the information processing is perceived as time consuming.
      Normally, it is possible to experience benefits when using IT, but this depends
      on either promoting or hindering factors, e.g. ease of use and ability to use it,
      equipment availability and technical functionality, as well as attitude.
      CONCLUSIONS: In summary, the findings showed that members of staff experience IT
      as a benefit when it simplifies their daily working routines and as a burden when
      it complicates their working processes. Whether IT complicates or simplifies
      their routines depends on influencing factors. The line between benefit and
      burden is semipermeable. The experiences differ according to duties and
      responsibilities.

PMID- 24947423
TI  - Open Access publishing.

PMID- 24947422
TI  - Epidemiological characteristics of severe fever with thrombocytopenia syndrome in
      Zhejiang Province, China.
AB  - OBJECTIVES: To summarize the epidemiological characteristics of severe fever with
      thrombocytopenia syndrome (SFTS) in Zhejiang Province, China. METHODS: A
      standardized questionnaire was used to collect information on demographic
      features, exposure history, clinical symptoms, and timelines of medical visits.
      Descriptive statistics were used to analyze the characteristics of SFTS. RESULTS:
      A total of 65 cases of SFTS were identified in Zhejiang Province from 2011 to
      2013, of whom 34 were male and 31 were female. The median age was 66 years and 60
      cases occurred in persons aged >= 50 years. The majority (91%) of SFTS cases
      occurred between May and August. With regard to exposure history, patients had
      pursued outdoor activities (63%), had a history of exposure to a tick (68%) or
      tick bite (29%), bred domestic animals (31%), or had a history of exposure to a
      mouse (57%), and some patients had a multi-exposure history. Approximately 98.46%
      of patients were hospitalized, and symptoms of the illness included fever (98%),
      fatigue (71%), chills (51%), etc. Two family clusters occurred, although there
      was no person-to-person transmission. CONCLUSIONS: In Zhejiang Province, SFTS is
      prevalent between May and August among elderly persons who live in hilly areas,
      and clinical features are not specific. More emphasis should be given to this
      disease and further training of medical personnel should be carried out to
      prevent misdiagnosis.

PMID- 24947424
TI  - Crimean-Congo hemorrhagic fever infections reported by ProMED.
AB  - OBJECTIVE: There are limited sources describing the global burden of emerging
      diseases. We reviewed the Crimean-Congo hemorrhagic fever virus (CCHFV)
      infections reported by ProMED and assessed the reliability of the data retrieved
      compared to published reports. We evaluated the effectiveness of ProMED as a
      source of epidemiological data by focusing on CCHFV infections. METHODS: Using
      the keywords "Crimean Congo hemorrhagic fever" and "Crimean Congo" in the ProMED
      search engine, we reviewed all the information about the news and harvested data
      using a structured form, including year, country, gender, occupation, the number
      of infected individuals, and the number of fatal cases. RESULTS: We identified
      383 entries reported between January 1998 and October 2013. A total 3426 infected
      cases were reported, with 451 fatal cases, giving an overall case fatality rate
      (CFR) of 13%. Out of 144 cases for which the gender was reported, 97 (67%) were
      male. Most of the cases were reported from Turkey, followed by Russia, Iran,
      Pakistan, and Afghanistan. CONCLUSIONS: Case reporting systems such as ProMED are
      useful to gather information and synthesize knowledge on the emerging infections.
      Although certain areas need to be improved, ProMED provided good information
      about Crimean-Congo hemorrhagic fever.

PMID- 24947425
TI  - Effect of CPAP on blood pressure in patients with minimally symptomatic
      obstructive sleep apnoea: a meta-analysis using individual patient data from four
      randomised controlled trials.
AB  - BACKGROUND: CPAP reduces blood pressure (BP) in patients with symptomatic
      obstructive sleep apnoea (OSA). Whether the same benefit is present in patients
      with minimally symptomatic OSA is unclear, thus a meta-analysis of existing trial
      data is required. METHODS: The electronic databases Medline, Embase and trial
      registries were searched. Trials were eligible if they included patients with
      minimally symptomatic OSA, had randomised them to receive CPAP or either sham
      CPAP or no CPAP, and recorded BP at baseline and follow-up. Individual
      participant data were obtained. Primary outcomes were absolute change in systolic
      and diastolic BP. FINDINGS: Five eligible trials were found (1219 patients) from
      which data from four studies (1206 patients) were obtained. Mean (SD) baseline
      systolic and diastolic BP across all four studies was 131.2 (15.8) mm Hg and 80.9
      (10.4) mm Hg, respectively. There was a slight increase in systolic BP of 1.1 mm
      Hg (95% CI -0.2 to 2.3, p=0.086) and a slight reduction in diastolic BP of 0.8 mm
      Hg (95% CI -1.6 to 0.1, p=0.083), although the results were not statistically
      significant. There was some evidence of an increase in systolic BP in patients
      using CPAP <4 h/night (1.5 mm Hg, 95% CI -0.0 to 3.1, p=0.052) and reduction in
      diastolic BP in patients using CPAP >4 h/night (-1.4 mm Hg, 95% CI -2.5 to -0.4,
      p=0.008). CPAP treatment reduced both subjective sleepiness (p<0.001) and OSA
      severity (p<0.001). INTERPRETATION: Although CPAP treatment reduces OSA severity
      and sleepiness, it seems not to have a beneficial effect on BP in patients with
      minimally symptomatic OSA, except in patients who used CPAP for >4 h/night.

PMID- 24947427
TI  - SVCT2 transporter expression is post-natally induced in cortical neurons and its
      function is regulated by its short isoform.
AB  - Different studies have demonstrated the importance of micronutrients, such as
      vitamins, for normal adult brain function and development. Vitamin C is not
      synthesized in the brain, but high levels are detected in this organ because of
      the existence of specific uptake mechanisms, which concentrate ascorbic acid from
      the bloodstream to the cerebrospinal fluid and then into neurons and glial cells.
      Two different isoforms of sodium-vitamin C cotransporters (SVCT1 and SVCT2) have
      been cloned. SVCT2 expression has been observed in the adult hippocampus and
      cortical neurons by in situ hybridization. In addition, the localization of SVCT2
      in the rat fetal brain has been studied by immunohistochemistry and in situ
      hybridization, demonstrating that SVCT2 is highly expressed in the ventricular
      and subventricular areas of the brain cortex. However, there are currently no
      immunohistochemical data regarding SVCT2 expression and function in the post
      natal brain. Therefore, we analyzed SVCT2 expression in the developing brain
      cortex of mice, and demonstrated an increase in SVCT2 mRNA in mice at 1-15 days
      of age. The expression of a short isoform, SVCT2sh, was also detected within the
      same period. SVCT2 expression was concentrated in neurons within the inner layer
      of the brain cortex. Both SVCT2 isoforms were coexpressed in N2a cells to obtain
      functional data. Fluorescence resonance energy transfer analysis revealed a
      molecular interaction between SVCT2wt and SVCT2sh. Finally, differences in
      transport ratios suggested that SVCT2sh expression inhibited ascorbic acid uptake
      in N2a cells when both isoforms were coexpressed. The sodium-vitamin C
      cotransporter, SVCT2, is induced in neurons within the inner layer of the brain
      cortex during post-natal development, mainly in pyramidal cortex neurons. Two
      different isoforms, SVCT2wt and SVCT2sh, were detected. Using in vitro studies,
      we suggest a molecular interaction between SVCT2wt and SVCT2sh, which may
      regulate the affinity of vitamin C uptake.

PMID- 24947428
TI  - The impact of the Maillard reaction on the in vitro proteolytic breakdown of
      bovine lactoferrin in adults and infants.
AB  - The Maillard reaction has been proposed as a natural pathway to functionalize
      proteins and modulate their proteolysis. Nevertheless, gaps in understanding the
      digestive fate of Maillard reaction products (MRPs) still exist, especially
      regarding bioactive proteins such as lactoferrin (LF). UV absorbance and SDS-PAGE
      were used to monitor reaction progression under mild thermal processing (60 
      degrees C, 79% RH). Dynamic light scattering showed that MRPs had increased
      colloidal size and turbidity at 3 < pH < 10. FRAP analysis and in vitro digestion
      experiments demonstrated that MRPs possessed improved antioxidant capacity and
      higher susceptibility to proteolysis to varying extents under adult conditions
      compared to infant conditions. Proteomic analyses of MRP digesta revealed altered
      enzymatic cleavage patterns with no pronounced changes in the formation of known
      bioactive peptides. These also indicated that MRPs may breakdown in the gastro
      intestinal tract to potentially form novel bioactive peptides. Overall, this work
      highlights that the Maillard reaction could be harnessed to modify the extent of
      proteolysis and bioactivity of proteins. 

PMID- 24947426
TI  - Structural and thermodynamic characterization of the recognition of the S100
      binding peptides TRTK12 and p53 by calmodulin.
AB  - Calmodulin (CaM) is a multifunctional messenger protein that activates a wide
      variety of signaling pathways in eukaryotic cells in a calcium-dependent manner.
      CaM has been proposed to be functionally distinct from the S100 proteins, a
      related family of eukaryotic calcium-binding proteins. Previously, it was
      demonstrated that peptides derived from the actin-capping protein, TRTK12, and
      the tumor-suppressor protein, p53, interact with multiple members of the S100
      proteins. To test the specificity of these peptides, they were screened using
      isothermal titration calorimetry against 16 members of the human S100 protein
      family, as well as CaM, which served as a negative control. Interestingly, both
      the TRTK12 and p53 peptides were found to interact with CaM. These interactions
      were further confirmed by both fluorescence and nuclear magnetic resonance
      spectroscopies. These peptides have distinct sequences from the known CaM target
      sequences. The TRTK12 peptide was found to independently interact with both CaM
      domains and bind with a stoichiometry of 2:1 and dissociations constants Kd,C
      term  = 2 +/- 1 uM and Kd,N-term  = 14 +/- 1 uM. In contrast, the p53 peptide was
      found to interact only with the C-terminal domain of CaM, Kd,C-term = 2 +/- 1 uM,
      25 degrees C. Using NMR spectroscopy, the locations of the peptide binding sites
      were mapped onto the structure of CaM. The binding sites for both peptides were
      found to overlap with the binding interface for previously identified targets on
      both domains of CaM. This study demonstrates the plasticity of CaM in target
      binding and may suggest a possible overlap in target specificity between CaM and
      the S100 proteins.

PMID- 24947430
TI  - Design and implementation of a 2-DOF PID compensation for magnetic levitation
      systems.
AB  - This paper employs a 2-DOF (degree of freedom) PID controller for compensating a
      physical magnetic levitation system. It is shown that because of having a
      feedforward gain in the proposed 2-DOF PID control, the transient performance of
      the compensated system can be changed in a desired manner unlike the conventional
      1-DOF PID control. It is also shown that for a choice of PID parameters, although
      the theoretical loop robustness is the same for both the compensated systems, in
      real-time, 2-DOF PID control may provide superior robustness if a suitable choice
      of the feedforward parameter is made. The results are verified through
      simulations and experiments. 

PMID- 24947431
TI  - RBFNDOB-based neural network inverse control for non-minimum phase MIMO system
      with disturbances.
AB  - An adaptive control strategy combining neural network inverse controller (NNIC)
      with RBFN disturbance observer (RBFNDOB) is developed for a multi-input-multi
      output (MIMO) system with non-minimum phase, internal and external disturbances
      in this paper. Since the inverse model of system is unstable due to the non
      minimum phase, a pseudo-plant is constructed, then the RBFN is used to identify
      the inverse model of pseudo-plant, which can track the parameter variations of
      system. By copying the structure and parameters of the identifier, the NNIC is
      obtained. Cascading the NNIC with the original plant, the MIMO system can be
      decoupled and linearized into independent SISO systems. For the independent
      decoupled system, the RBFNDOB employs a RBFN to observe the external disturbances
      and this estimate value is used as a feed-forward compensation term in
      controller. The case study on ball mill grinding circuit is presented. The
      effectiveness of the proposed method is demonstrated by simulation results and
      comparisons. 

PMID- 24947429
TI  - The dynamic proliferation of CanSINEs mirrors the complex evolution of Feliforms.
AB  - BACKGROUND: Repetitive short interspersed elements (SINEs) are retrotransposons
      ubiquitous in mammalian genomes and are highly informative markers to identify
      species and phylogenetic associations. Of these, SINEs unique to the order
      Carnivora (CanSINEs) yield novel insights on genome evolution in domestic dogs
      and cats, but less is known about their role in related carnivores. In
      particular, genome-wide assessment of CanSINE evolution has yet to be completed
      across the Feliformia (cat-like) suborder of Carnivora. Within Feliformia, the
      cat family Felidae is composed of 37 species and numerous subspecies organized
      into eight monophyletic lineages that likely arose 10 million years ago. Using
      the Felidae family as a reference phylogeny, along with representative taxa from
      other families of Feliformia, the origin, proliferation and evolution of CanSINEs
      within the suborder were assessed. RESULTS: We identified 93 novel intergenic
      CanSINE loci in Feliformia. Sequence analyses separated Feliform CanSINEs into
      two subfamilies, each characterized by distinct RNA polymerase binding motifs and
      phylogenetic associations. Subfamily I CanSINEs arose early within Feliformia but
      are no longer under active proliferation. Subfamily II loci are more recent,
      exclusive to Felidae and show evidence for adaptation to extant RNA polymerase
      activity. Further, presence/absence distributions of CanSINE loci are largely
      congruent with taxonomic expectations within Feliformia and the less resolved
      nodes in the Felidae reference phylogeny present equally ambiguous CanSINE data.
      SINEs are thought to be nearly impervious to excision from the genome. However,
      we observed a nearly complete excision of a CanSINEs locus in puma (Puma
      concolor). In addition, we found that CanSINE proliferation in Felidae frequently
      targeted existing CanSINE loci for insertion sites, resulting in tandem arrays.
      CONCLUSIONS: We demonstrate the existence of at least two SINE families within
      the Feliformia suborder, one of which is actively involved in insertional
      mutagenesis. We find SINEs are powerful markers of speciation and conclude that
      the few inconsistencies with expected patterns of speciation likely represent
      incomplete lineage sorting, species hybridization and SINE-mediated genome
      rearrangement.

PMID- 24947432
TI  - Input-output finite-time stabilization of linear systems with finite-time
      boundedness.
AB  - The paper presents linear system Input-Output Finite-Time Stabilization (IO-FTS)
      method under Finite-Time Boundedness (FTB) constraint. A state feedback
      controller is designed, via Linear Matrix Inequalities (LMIs), to guarantee the
      system both IO-FTS and FTB. The proposed methods are applied to the guidance
      design of a class of terminal guidance systems to suppress disturbances with IO
      FTS method and FTB constraints simultaneously satisfied. The simulation results
      illustrate the effectiveness of the proposed methods. 

PMID- 24947435
TI  - Direct formation of small Cu2O nanocubes, octahedra, and octapods for efficient
      synthesis of triazoles.
AB  - In most studies describing the preparation of Cu2O crystals of various
      morphologies, the particle sizes are normally hundreds of nanometers to
      micrometers due to rapid particle growth, so they are not exactly nanocrystals.
      Here we report surfactant-free formation of sub-100 nm Cu2O nanocrystals with
      systematic shape evolution from cubic to octahedral structures by preparing an
      aqueous mixture of Cu(OAc)2, NaOH, and N2H4 solution. Adjustment of the hydrazine
      volume enables the particle shape control. Uniform nanocubes and octahedra were
      synthesized with edge lengths of 37 and 67 nm, respectively. Novel Cu2O octapods
      with an edge length of 135 nm were also produced by mixing CuCl2 solution, SDS
      surfactant, NaOH solution, and NH2OH . HCl reductant solution. All of them are
      nearly the smallest Cu2O nanocrystals of the same shapes ever reported. These
      small cubes, octahedra, and octapods were employed as catalysts in the direct
      synthesis of 1,2,3-triazoles from the reaction of alkynes, organic halides, and
      NaN3 at 55  degrees C. All of them displayed high product yields in short
      reaction times. The octahedra enclosed by the {111} facets are the best
      catalysts, and can catalyze this cycloaddition reaction with high yields in just
      2 h when different alkynes were used to make diverse triazole products. Hence,
      the small Cu2O particles provide time-saving, energy-efficient, and high product
      yield benefits to organocatalysis.

PMID- 24947433
TI  - Variation at ABO histo-blood group and FUT loci and diffuse and intestinal
      gastric cancer risk in a European population.
AB  - ABO blood serotype A is known to be associated with risk of gastric cancer (GC),
      but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and
      genes which are involved in Lewis antigen formation [and in Helicobacter pylori
      (H. pylori) binding and pathogenicity] may be related to GC risk in a European
      population. The authors conducted an investigation of 32 variants at ABO and FUT1
      7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested
      within the EPIC cohort (the EPIC-Eurgast study). Four variants (including
      rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20
      2.80) were associated with diffuse-type GC; however, conditional models with
      other ABO variants indicated that the associations were largely due to allelic
      blood group A. One variant in FUT5 was also associated with diffuse-type GC, and
      four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal
      type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated
      with H. pylori infection status in controls, and two of these (in FUT3 and FUT6)
      were weakly associated with intestinal-type GC risk. None of the individual
      variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however,
      after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)]
      were significantly associated with diffuse- and intestinal-type GC, respectively.
      Replication and functional studies are therefore recommended to clarify the role
      of ABO and FUT alleles in H. pylori infection and subtype-specific gastric
      carcinogenesis.

PMID- 24947434
TI  - Prevention of age-related endothelial dysfunction by habitual aerobic exercise in
      healthy humans: possible role of nuclear factor kappaB.
AB  - Habitual aerobic exercise prevents age-related impairments in endothelium
      dependent dilation (EDD). We have hypothesized that the pro-inflammatory
      transcription factor nuclear factor kappaB (NF-kappaB) impairs EDD with sedentary
      aging, and habitual aerobic exercise prevents this age-related suppression of EDD
      by NF-kappaB. To test this hypothesis, we have inhibited NF-kappaB signalling via
      oral salsalate administration in healthy older aerobic exercise-trained adults
      (OT, n=14, 58 +/- 2 years), older non-exercising adults (ON, n=16, 61 +/- 1
      years) and young non-exercising controls (YN, n=8, 23 +/- 1 years). Salsalate
      reduced endothelial cell expression of NF-kappaB p65 by ~25% in ON (P<0.05) but
      did not significantly change expression in OT or YN (P>0.05). EDD, assessed by
      brachial artery flow-mediated dilation (FMD), was improved by salsalate in ON
      (4.0 +/- 0.7% compared with 6.8 +/- 0.7%, placebo compared with salsalate,
      P<0.001) but did not change with salsalate in OT or YN (OT: 7.2 +/- 0.7% compared
      with 7.7 +/- 0.6%; YN: 7.6 +/- 0.9% compared with 8.1 +/- 0.8%; placebo compared
      with salsalate, P>0.05). Endothelium-independent dilation was not affected by
      salsalate in any group (P>0.05). In ON, vitamin C infusion improved FMD by ~30%
      during placebo (P<0.001) but had no affect during salsalate (P>0.05). In OT and
      YN, vitamin C infusion did not affect FMD during either placebo or salsalate
      (P>0.05). Salsalate reduced endothelial cell nitrotyrosine content by ~25% and
      NADPH oxidase p47phox expression by ~30% in ON (P<0.05) but had no effect in OT
      or YN (P>0.05). Our results suggest that endothelial NF-kappaB signalling is
      associated with oxidative stress-related impairment of EDD in healthy non
      exercising but not aerobically exercising older adults. This may be a key
      mechanism by which regular aerobic exercise preserves endothelial function and
      reduces cardiovascular risk with aging.

PMID- 24947436
TI  - Pharmacokinetics and efficacy of Bioerodible Dexamethasone implant in
      Concanavalin A-induced uveitic cataract rabbit model.
AB  - PURPOSE: To advance therapy for the treatment of concurrent uveitis and post
      cataract surgical inflammation; we evaluated pharmacokinetics and
      pharmacodynamics of Bioerodible Dexamethasone Implant (BDI) containing 0.3 mg of
      dexamethasone (DXM) in Concanavalin A (Con A) induced uveitis followed by
      phacoemulsification in New Zealand White (NZW) rabbits. METHODS: The BDI was
      implanted in the inferior fornix of the capsular bag after intravitreal injection
      of Con A and ensuing phacoemulsification in NZW rabbits; standard-of-care topical
      0.1% dexamethasone drops served as control. DXM was quantified by liquid
      chromatography-tandem mass spectrometry and pharmacokinetics of DXM in disease
      vs. healthy eyes was compared. All eyes were assessed clinically using slit lamp
      biomicroscopy and Draize scoring scale. Retinal thickness and histological
      analyses were performed to evaluate retinal edema, inflammation and implant
      biocompatibility respectively. RESULTS: In Con A-induced inflammatory uveitic
      cataract model the BDI controlled anterior and posterior segment inflammation as
      well as retinal thickening more effectively than topical drops. The exposure
      (AUC0-t) of DXM with BDI is superior in all ocular tissues, while topical drops
      did not achieve therapeutic posterior segment levels and did not control
      inflammation nor prevent retinal edema and architectural disruption. CONCLUSIONS:
      Our results demonstrate the superiority of the BDI in suppressing Con A-induced
      inflammation and retinal edema in NZW rabbits and highlight the need for
      sustained bidirectional delivery of potent anti-inflammatory agents for 5 to 6
      weeks to optimize clinical outcomes.

PMID- 24947437
TI  - Optimization of impedance spectroscopy techniques for measuring cutaneous
      micropore formation after microneedle treatment in an elderly population.
AB  - PURPOSE: The objective of this study was to optimize a reproducible impedance
      spectroscopy method in elderly subjects as a means to evaluate the effects of
      microneedles on aging skin. METHODS: Human volunteers were treated with
      microneedles at six sites on the upper arm. Repeated impedance measurements were
      taken pre- and post-microneedle insertion. Two electrode types were evaluated
      (dry vs. gel), using either light or direct pressure to maintain contact between
      the electrode and skin surface. Transepidermal water loss (TEWL) was measured as
      a complementary technique. RESULTS: Five control subjects and nine elderly
      subjects completed the study. Microneedle insertion produced a significant
      decrease in impedance from baseline in all subjects (p < 0.05, regardless of
      electrode type or pressure application), confirming micropore formation. This was
      supported by a complementary significant increase in TEWL (p < 0.05). The
      gel*direct condition produced the lowest variability between measurements, as
      demonstrated by a coefficient of variation of 3.8% and 3.5% (control and elderly
      subjects, respectively). This was lower than variation between TEWL measurements
      at the same sites: 19.8% and 21.6% (control and elderly subjects, respectively).
      CONCLUSIONS: Impedance spectroscopy reproducibly measures micropore formation in
      elderly subjects, which will be essential for future studies describing
      microneedle-assisted transdermal delivery in aging populations.

PMID- 24947438
TI  - Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult
      onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective
      drug screening and identifies a SIR-2.1-independent action of resveratrol.
AB  - Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder
      characterized by progressive neuronal dysfunction and premature death. Recently,
      the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes
      cysteine string protein alpha. We show here that mutating dnj-14, the
      Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a
      small impairment of locomotion and neurotransmission. Mutant dnj-14 worms also
      exhibited age-dependent neurodegeneration of sensory neurons, which was preceded
      by severe progressive chemosensory defects. A focussed chemical screen revealed
      that resveratrol could ameliorate dnj-14 mutant phenotypes, an effect mimicked by
      the cAMP phosphodiesterase inhibitor, rolipram. In contrast to other worm
      neurodegeneration models, activation of the Sirtuin, SIR-2.1, was not required,
      as sir-2.1; dnj-14 double mutants showed full lifespan rescue by resveratrol. The
      Sirtuin-independent neuroprotective action of resveratrol revealed here suggests
      potential therapeutic applications for ANCL and possibly other human
      neurodegenerative diseases. 

PMID- 24947440
TI  - Membrane sensors based on Schiff bases as chelating ionophores--a review.
AB  - The development of chemical sensors has received widespread attention during the
      past two decades because of their extensive use in environmental monitoring and
      clinical analysis via rapid, accurate, reproducible, and low-cost methods.
      Chemically modified CPEs have frequently been employed as potentiometric sensors
      in trace analysis for metal ions, organic pollutants and biological substances.
      Most of these electrodes are operated via the ion-exchange process of the active
      component incorporated into the carbon paste matrix. This review article
      concentrates on such achievements in the context of the general development
      across the field. An overview of potentiometric sensors that are capable of
      detecting metal ions in environmental samples is presented and discussed. A
      survey on important advances in potentiometric sensors with regard to high
      selectivity, lower detection limit, and fast response time is presented in this
      review article. 

PMID- 24947439
TI  - Genome-wide investigation of genetic changes during modern breeding of Brassica
      napus.
AB  - KEY MESSAGE: Considerable genome variation had been incorporated within rapeseed
      breeding programs over past decades. In past decades, there have been substantial
      changes in phenotypic properties of rapeseed as a result of extensive breeding
      effort. Uncovering the underlying patterns of allelic variation in the context of
      genome organisation would provide knowledge to guide future genetic improvement.
      We assessed genome-wide genetic changes, including population structure, genetic
      relatedness, the extent of linkage disequilibrium, nucleotide diversity and
      genetic differentiation based on F ST outlier detection, for a panel of 472
      Brassica napus inbred accessions using a 60 k Brassica Infinium(r) SNP array. We
      found genetic diversity varied in different sub-groups. Moreover, the genetic
      diversity increased from 1950 to 1980 and then remained at a similar level in
      China and Europe. We also found ~6-10 % genomic regions revealed high F ST
      values. Some QTLs previously associated with important agronomic traits
      overlapped with these regions. Overall, the B. napus C genome was found to have
      more high F ST signals than the A genome, and we concluded that the C genome may
      contribute more valuable alleles to generate elite traits. The results of this
      study indicate that considerable genome variation had been incorporated within
      rapeseed breeding programs over past decades. These results also contribute to
      understanding the impact of rapeseed improvement on available genome variation
      and the potential for dissecting complex agronomic traits.

PMID- 24947441
TI  - Trophic action of sympathetic nerves reduces arterial smooth muscle Ca(2+)
      sensitivity during early post-natal development in rats.
AB  - AIM: A decrease in the Ca(2+) sensitivity of smooth muscle contraction is a
      hallmark of functional remodelling of blood vessels during development. However,
      the responsible factors are largely unknown. Here, we tested the hypothesis that
      the post-natal decline of arterial Ca(2+) sensitivity is the result of trophic
      effects of sympathetic nerves. METHODS: Contractile responses, intracellular
      Ca(2+) levels and protein expression profiles were compared in saphenous arteries
      from young (1- and 2-week-old) and adult rats using wire myography, Ca(2+)
      fluorimetry and Western blotting respectively. RESULTS: We observed a lower
      Ca(2+) sensitivity of contractions induced by methoxamine, an agonist of alpha1 
      adrenoceptors, and U46619, an agonist of thromboxane A2 receptors, in arteries
      from adult as compared to young animals. Post-natal maturation was associated
      with stronger expression of regulatory proteins mediating Ca(2+) -dependent
      contraction (myosin light chain kinase (MLCK), myosin targeting subunit (MYPT1)
      and h-caldesmon) and weaker expression of proteins regulating Ca(2+) -independent
      contraction (Rho kinase, extracellular-regulated kinases (ERK1/2) and mitogen
      activated protein kinases p38 MAPK) in vessels from adult rats. To eliminate the
      trophic action of sympathetic nerves, we performed lumbar sympathectomy in adult
      rats. This resulted in higher Ca(2+) sensitivity of agonist-induced contractions
      in denervated as compared to control arteries. Furthermore, denervated arteries
      contained less MLCK, MYPT1 and h-caldesmon and more ERK1/2 and p38 MAPK.
      CONCLUSIONS: Sympathetic denervation reverses developmental changes both in
      Ca(2+) sensitivity and in the expression of regulatory proteins back to the early
      post-natal phenotype in the rat saphenous artery. We conclude that trophic
      effects of sympathetic nerves govern functional remodelling of arteries during
      early post-natal development.

PMID- 24947442
TI  - Predictors of hyperglycaemic individuals who do not follow up with physicians
      after screening in Japan: a cohort study.
AB  - AIMS: Although people screened as being hyperglycaemic often fail to follow up
      with physicians for clinical assessment, epidemiologic findings on the frequency
      and predictors of not following up (hereafter, "no follow-up") are lacking. The
      purpose of this study was to examine the no follow-up rate with physicians after
      screening for diabetes and predictors of no follow-up. METHODS: We assessed cases
      of no follow-up with physicians within six months after screening based on
      medical claims data from employee-based social health insurance programs in
      Japan, for people aged 20 to 68 years from 2005 to 2010. RESULTS: Among 3878
      screened participants with hyperglycaemia, 2527 (65%) did not follow up with
      their physicians within six months after screening. Multiple logistic regression
      analysis revealed that younger age and lower blood glucose level predicted no
      follow-up among both men and women, while lower body mass index and negative
      proteinuria also predicted no follow-up among men. Treatment for dyslipidaemia
      facilitated follow-up among both genders, and treatment for hypertension or
      depression facilitated follow-up among men. CONCLUSIONS: Approximately two thirds
      of individuals screened as having hyperglycaemia did not follow up with their
      physicians within six months after screening. Predictors of no follow-up were
      younger age and milder hyperglycaemia. Being on treatment for co-morbidities
      tended to facilitate follow-up.

PMID- 24947443
TI  - Saxagliptin improves glycemic control by modulating postprandial glucagon and C
      peptide levels in Chinese patients with type 2 diabetes.
AB  - AIMS: Saxagliptin reduced glycated hemoglobin (HbA1c), fasting plasma glucose
      (FPG), and postprandial glucose (PPG) in Asian patients with type 2 diabetes
      mellitus (T2DM). To understand the physiology of this effect, indices of alpha-
      and beta-cell function were measured in a subpopulation of Chinese patients
      following a noodle mixed-meal tolerance test. METHODS: Data from Chinese patients
      were pooled from two phase 3, 24-week studies of saxagliptin 5mg/d as monotherapy
      in drug-naive patients and as add-on to metformin in patients inadequately
      controlled with metformin alone. The end points for beta- and alpha-cell function
      were change from baseline in C-peptide, insulin, and glucagon areas under the
      curve from 0 to 180 min (AUC0-180), insulinogenic index, and insulin sensitivity
      from Matsuda index after a mixed meal. Also glycemic variables, HbA1c, FPG, and
      PPG (AUC0-180), and homeostasis model assessment (HOMA) 2beta were measured.
      RESULTS: At 24 weeks, greater improvements in adjusted mean change from baseline
      HbA1c (difference vs placebo [95% CI], -0.33% [-0.50%, -0.17%], [-4 (-5.5, -1.9)
      mmol/mol], P<0.0001), FPG (-0.41 [-0.78, -0.03] mmol/L, P=0.03), PPG AUC0-180 (
      168 [-245, -91.8] mmol min/L, P<0.0001), C-peptide AUC0-180 (19.7 [5.2, 34.2]
      nmol min/L, P=0.008), insulinogenic index (0.06% [0.02%, 0.09%], P=0.002), and
      greater suppression of glucagon secretion (glucagon AUC0-180, -322 [-493.6, 
      150.7] pmol min/L, P=0.0003) were observed with saxagliptin versus placebo.
      CONCLUSION: In Chinese patients with T2DM, saxagliptin as monotherapy or as add
      on to metformin improved glycemic control by modulating alpha- and beta-cell
      function.

PMID- 24947445
TI  - Microfluidic molding of photonic microparticles with engraved elastomeric
      membranes.
AB  - A microfluidic approach to prepare photonic microparticles by repeated molding of
      photocurable colloidal suspension is reported. An elastomeric membrane with
      negative relieves which vertically separates two microfluidic channels is
      integrated; bottom channel is used for suspension flow, whereas water-filled top
      channel is used for pneumatic actuation of the membrane. Upon pressurization of
      the top channel, membrane is deformed to confine the suspension into its negative
      relieves, which is then polymerized by UV irradiation, making microparticles with
      mold shape. The microparticles are released from the mold by relieving the
      pneumatic pressure and flows through the bottom channel. This one cycle of
      molding, polymerization, and release can be repeatedly performed in microfluidic
      device of which pneumatic valves are actuated in a programmed manner. The
      microparticles exhibit structural colors when the suspension contains high
      concentration of silica nanoparticles; the nanoparticles form regular arrays and
      the microparticles reflect specific wavelength of light as a photonic crystals.
      The silica nanoparticles can be selectively removed to make pronounced structural
      colors. In addition, the microparticles can be further functionalized by
      embedding magnetic particles in the matrix of the microparticles, enabling the
      remote control of rotational motion of microparticles. 

PMID- 24947444
TI  - Placental heme receptor LRP1 correlates with the heme exporter FLVCR1 and
      neonatal iron status.
AB  - LDL receptor-related protein 1 (LRP1) is a transmembrane receptor highly
      expressed in human placenta. It was recently found to be the receptor for heme
      and its plasma-binding protein hemopexin (Hx) and is integral to systemic heme
      clearance. Little is known about systemic concentrations of Hx during pregnancy
      and whether maternal Hx and placental LRP1 contributes to fetal iron (Fe)
      homeostasis during pregnancy. We hypothesized that placental LRP1 would be
      upregulated in maternal/neonatal Fe insufficiency and would be related to
      maternal circulating Hx. Placental LRP1 expression was assessed in 57 pregnant
      adolescents (14-18 years) in relationship with maternal and cord blood Fe status
      indicators (hemoglobin (Hb), serum ferritin, transferrin receptor), the Fe
      regulatory hormone hepcidin and serum Hx. Hx at mid-gestation correlated
      positively with Hb at mid-gestation (r=0.35, P=0.02) and Hx at delivery
      correlated positively with cord hepcidin (r=0.37, P=0.005). Placental LRP1
      protein expression was significantly higher in women who exhibited greater
      decreases in serum Hx from mid-gestation to term (r=0.28, P=0.04). Significant
      associations were also found between placental LRP1 protein with cord hepcidin
      (r=-0.29, P=0.03) and placental heme exporter feline leukemia virus C receptor 1
      (r=0.34, P=0.03). Our data are consistent with a role for placental heme Fe
      utilization in supporting fetal Fe demands. 

PMID- 24947446
TI  - Role of hepatic blood flow and metabolism in the pharmacokinetics of ten drugs in
      lean, aged and obese rats.
AB  - 1. The effect of age and obesity on the pharmacokinetics (PK), hepatic blood flow
      (HBF) and liver metabolism of 10 compounds was determined in rats. The animals
      fed a high-fat diet were defined as the diet-induced obese (DIO) group, while the
      animals that were aged similar to the DIO rats but not fed with high-fat diet
      were called the age-matched (AM) group. 2. The clearance (CL) values of high CL
      compounds (CL > 50 mL/min/kg, namely propranolol, diazepam, phenytoin,
      ethinylestradiol, lorcaserin and fenfluramine) decreased significantly (1.5- to 6
      fold) in DIO and AM rats as compared to lean rats, while there was no clear trend
      for change in CL for the low-to-moderate CL compounds (CL < 50 mL/min/kg, namely
      atenolol, chlorzoxazone, vancomycin and sibutramine). Hepatocytes incubations
      revealed a change in half life (t1/2) only for phenytoin. The body weight
      normalized liver weights and HBF of AM and DIO rats were found to be 2- to 3-fold
      lower than in lean rats. 3. Our findings suggest that age, and diet to a lesser
      extent, can reduce HBF and body normalized liver weights and, hence, also reduce
      CL values for high CL compounds in rats.

PMID- 24947448
TI  - Safe and successful endoscopic initial treatment and long-term eradication of
      gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2
      cyanoacrylate) injection.
AB  - OBJECTIVE: Optimal endoscopic treatment of gastric varices is still not
      standardized nowadays. Actively bleeding varices may prohibit a successful
      endoscopic injection therapy of Histoacryl(r) (N-butyl-2-cyanoacrylate). Since
      2006, we have treated gastric varices by standardized endoscopic ultrasound (EUS)
      guided Histoacryl injection therapy without severe adverse events. MATERIAL AND
      METHODS: We present a large single-center cohort over 7 years with a standardized
      EUS-guided sclerotherapy of all patients with gastric varices. Application was
      controlled by fluoroscopy to immediately detect any glue embolization. Only
      perforating veins located within the gastric wall were treated. In the follow up,
      we repeated this treatment until varices were eradicated. RESULTS: Utmost
      patients (36 of 40) were treated during or within 24 h of active bleeding. About
      32.5% of patients were treated while visible bleeding. Histoacryl injection was
      always technically successful and only two patients suffered a minor
      complication. Acute bleeding was stopped in all patients. About 15% (6 of 40) of
      patients needed an alternative rescue treatment in the longer course. Three
      patients got a transjugular portosystemic shunt and another three underwent an
      orthotopic liver transplantation. Mean long-term survival of 60 months was
      excellent. CONCLUSION: Active bleeding of gastric varices can be treated
      successfully without the necessity of gastric rinsing with EUS-guided injection
      of Histoacryl.

PMID- 24947447
TI  - Intervention to reduce excessive alcohol consumption and improve comorbidity
      outcomes in hypertensive or depressed primary care patients: two parallel cluster
      randomized feasibility trials.
AB  - BACKGROUND: Many primary care patients with raised blood pressure or depression
      drink potentially hazardous levels of alcohol. Brief interventions (BI) to reduce
      alcohol consumption may improve comorbid conditions and reduce the risk of future
      alcohol problems. However, research has not established their effectiveness in
      this patient population. This study aimed to establish the feasibility of
      definitive trials of BI to reduce excessive drinking in primary care patients
      with hypertension or mild to moderate depression. METHODS: Thirteen general
      practices in North East England were randomized to the intervention or control
      arm of one of two parallel pilot trials. Adult patients drinking excessively and
      diagnosed with hypertension or mild-to-moderate depression received the Alcohol
      Use Disorders Identification Test (AUDIT) by postal survey. Consenting
      respondents scoring more than 7 on AUDIT (score range 0 to 40) received brief
      alcohol consumption advice plus an information leaflet (intervention) or an
      information leaflet alone (control) with follow-up at six months. Measurements
      included the numbers of patients eligible, recruited, and retained, and the AUDIT
      score and systolic/diastolic blood pressure of each patient or the nine-item
      Patient Health Questionnaire (PHQ-9) score. Acceptability was assessed via
      practitioner feedback and patient willingness to be screened, recruited, and
      retained at follow-up. RESULTS: In the hypertension trial, 1709 of 33,813 adult
      patients (5.1%) were eligible and were surveyed. Among the eligible patients, 468
      (27.4%) returned questionnaires; 166 (9.6% of those surveyed) screened positively
      on AUDIT and 83 (4.8% of those surveyed) were recruited (50.0% of positive
      screens). Sixty-seven cases (80.7% of recruited patients) completed follow-up at
      six months. In the depression trial, 1,044 of 73,146 adult patients (1.4%) were
      eligible and surveyed. Among these eligible patients, 215 (20.6%) responded; 104
      (10.0% of those surveyed) screened positively on AUDIT and 29 (2.8% of those
      surveyed) were recruited (27.9% of positive screens). Nineteen cases (65.5% of
      recruited patients) completed follow-up at six months. CONCLUSIONS: Recruitment
      and retention rates were higher in the hypertension trial than in the depression
      trial. A full brief intervention trial appears feasible for primary care patients
      with hypertension who drink excessively. High AUDIT scores in the depression
      trial suggest the importance of alcohol intervention in this group. However,
      future work may require alternative screening and measurement procedures. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN89156543; registered 21 October
      2013.

PMID- 24947449
TI  - Neurofibromin inactivation impairs osteocyte development in Nf1Prx1 and Nf1Col1
      mouse models.
AB  - Neurofibromin has been identified as a critical regulator of osteoblast
      differentiation. Osteoblast specific inactivation of neurofibromin in mice
      results in a high bone mass phenotype and hyperosteoidosis. Here, we show that
      inactivation of the Nf1 gene also impairs osteocyte development. We analyzed
      cortical bone tissue in two conditional mouse models, Nf1Prx1 and Nf1Col1, for
      morphological and molecular effects. Backscattered electron microscopy revealed
      significantly enlarged osteocyte lacunae in Nf1Prx1 and Nf1Col1 mice (level E2:
      ctrl=1.90+/-0.52%, Nf1Prx1=3.40+/-0.95%; ctrl 1.60+/-0.47%, Nf1Col1 2.46+/
      0.91%). Moreover, the osteocyte lacunae appeared misshaped in Nf1Prx1 and Nf1Col1
      mice as indicated by increased Feret ratios. Strongest osteocyte and dendritic
      network disorganization was observed in proximity of muscle attachment sites in
      Nf1Prx1 humeri. In contrast to control cells, Nf1Prx1 osteocytes contained
      abundant cytosolic vacuoles and accumulated immature organic matrix within the
      perilacunar space, a phenotype reminiscent of the hyperosteoidosis shown Nf1
      deficient mice. Cortical bone lysates further revealed approx. twofold
      upregulated MAPK signalling in osteocytes of Nf1Prx1 mice. This was associated
      with transcriptional downregulation of collagens and genes involved in mechanical
      sensing in Nf1Prx1 and Nf1Col1 bone tissue. In contrast, matrix gla protein
      (MGP), phosphate regulating endopeptidase homolog, X-linked (PHEX), and genes
      involved in lipid metabolism were upregulated. In line with previously described
      hyperactivation of Nf1 deficient osteoblasts, systemic plasma levels of the bone
      formation markers osteocalcin (OCN) and procollagen typ I N-propeptide (PINP)
      were approx. twofold increased in Nf1Prx1 mice. Histochemical and molecular
      analysis ascertained that osteocytes in Nf1Prx1 cortical bone were viable and did
      not undergo apoptosis or autophagy. We conclude that loss of neurofibromin is not
      only critical for osteoblasts but also hinders normal osteocyte development.
      These findings expand the effect of neurofibromin onto yet another cell type
      where it is likely involved in the regulation of mechanical sensing, bone matrix
      composition and mechanical resistance of bone tissue. 

PMID- 24947451
TI  - Response to editorial comment from Dr Todenhofer and Dr Schwentner to recurrence
      and progression in patients with non-muscle invasive bladder cancer: prognostic
      models including multicolor fluorescence in situ hybridization molecular grading.

PMID- 24947450
TI  - Interrelation between external oscillatory muscle coupling amplitude and in vivo
      intramedullary pressure related bone adaptation.
AB  - Interstitial bone fluid flow (IBFF) is suggested as a communication medium that
      bridges external physical signals and internal cellular activities in the bone,
      which thus regulates bone remodeling. Intramedullary pressure (ImP) is one main
      regulatory factor of IBFF and bone adaptation related mechanotransduction. Our
      group has recently observed that dynamic hydraulic stimulation (DHS), as an
      external oscillatory muscle coupling, was able to induce local ImP with minimal
      bone strain as well as to mitigate disuse bone loss. The current study aimed to
      evaluate the dose dependent relationship between DHS's amplitude, i.e., 15 and
      30mmHg, and in vivo ImP induction, as well as this correlation on bone's
      phenotypic change. Simultaneous measurements of ImP and DHS cuff pressures were
      obtained from rats under DHS with various magnitudes and a constant frequency of
      2Hz. ImP inductions and cuff pressures upon DHS loading showed a positively
      proportional response over the amplitude sweep. The relationship between ImP and
      DHS cuff pressure was evaluated and shown to be proportional, in which ImP was
      raised with increases of DHS cuff pressure amplitudes (R(2)=0.98). A 4-week in
      vivo experiment using a rat hindlimb suspension model demonstrated that the
      mitigation effect of DHS on disuse trabecular bone was highly dose dependent and
      related to DHS's amplitude, where a higher ImP led to a higher bone volume. This
      study suggested that sufficient physiological DHS is needed to generate ImP.
      Oscillatory DHS, potentially induces local fluid flow, has shown dose dependence
      in attenuation of disuse osteopenia. 

PMID- 24947452
TI  - Surgical management of superior vena cava syndrome following pacemaker lead
      infection: a case report and review of the literature.
AB  - Superior vena cava (SVC) syndrome is a known but rare complication of pacemaker
      lead implantation, accounting for approximately less than 0.5% of cases. Its
      pathophysiology is due to either infection or endothelial mechanical stress,
      causing inflammation and fibrosis leading to thrombosis, and therefore stenosis
      of the SVC. Due to the various risks including thrombo-embolic complications and
      the need to provide symptomatic relief, medical and surgical interventions are
      sought early. We present the case of a 48-year Caucasian male who presented with
      localised swelling and pain at the site of pacemaker implantation. Inflammatory
      markers were normal, but diagnostic imaging revealed three masses along the
      pacemaker lead passage. A surgical approach using cardiopulmonary bypass and
      circulatory arrest was used to remove the vegetations. Culture from the
      vegetations showed Staphylococcus epidermidis. The technique presented here
      allowed for safe and effective removal of both the thrombus and infected pacing
      leads, with excellent exposure and minimal post-procedure complications. 

PMID- 24947453
TI  - Comparison of autogeneous and homogeneous nasal dorsal onlay grafts in an
      experimental design.
AB  - An experimental model was used for the comparative evaluation of autogeneous and
      homogeneous nasal dorsal onlay cartilage grafts. This study was conducted on 18
      adult white New Zealand male rabbits. Nasal septal cartilage (NSC), sliced nasal
      septal cartilage (SNSC) and auricular cartilage (AC) grafts were prepared in
      autogeneous and homogeneous forms and placed into the subcutaneous pockets of the
      nasal dorsum of rabbits. After a period of 3 months, the animals were painlessly
      killed, and each site was analyzed histologically for inflammation,
      neovascularization, fibrosis and resorption. Inflammation, fibrosis and
      neovascularization were found to be significantly more extensive in the
      homogeneous graft groups and autogeneous SNSC group 3 months after implantation.
      Resorption was significantly high in both homogeneous and autogeneous AC groups
      and significantly low in the autogeneous and homogeneous SNSC groups. There was
      no significant difference between the homogeneous and autogeneous grafts in terms
      of resorption rates. In conclusion, the results of this experimental study
      demonstrate that resorption was lesser than expected in the sliced cartilage
      graft and that homologous cartilage graft applications had activity and
      reliability similar to that of autogenous cartilage grafts.

PMID- 24947455
TI  - Latent profiles of parental self-efficacy and children's multisource-evaluated
      social competence.
AB  - BACKGROUND: The interrelation between mothers' parental self-efficacy (PSE) and
      their school-aged children's well-being has been repeatedly proved. The lack of
      research in this area situates mainly on the absence of fathers, non-existent
      family-level studies, the paucity of independent evaluators, and the use of
      global PSE estimates. AIMS: We aimed to qualitatively identify different
      subgroups of mothers, fathers, and couples based on their PSE factors.
      Furthermore, we aimed to study the interrelations between these PSE subgroups and
      children's school-related social competence evaluated by the children themselves
      as well as by their peers, teachers, and parents. SAMPLE: Sample (n = 981; girls
      n = 467; boys n = 514) consisted of fourth-grade (mean age, 10 years old)
      children, their teachers, peers, and parents (mothers n = 876; fathers n = 696).
      METHODS: Latent profile analysis was used to identify parents with similar
      patterns of PSE. The data of mothers and fathers were modelled separately and as
      a family-level combination. Interrelations between PSE subgroups and children's
      multisource-evaluated social competence were analysed with group comparisons.
      RESULTS: Separate subgroups of mothers, fathers, and couples were identified and
      labelled based on their PSE profiles. Subgroups were found to differ among
      mothers' age and education and children's academic skills. Most of the
      interrelations between PSE subgroups and children's social competence were
      statistically significant in a sense that children of parents with strong PSE
      were evaluated as more prosocial and less antisocial than others. CONCLUSION:
      Despite new perspectives on parents' PSE estimates and use of behaviour
      evaluators outside the family system, the interrelation between positive PSE and
      children's social competence and learning remains strong.

PMID- 24947456
TI  - Evaluating the potential risks of bubble studies during echocardiography.
AB  - OBJECTIVE: Cardiac shunts are often identified using bubble studies in
      echocardiography, with agitated saline. Previous studies have recommended various
      safe amounts of agitated saline. This poses a potential risk for air
      microembolism. The purpose of this study was to quantify the bubbles created by
      various quantities of agitated saline. METHODS: A closed circuit was constructed
      with a HeartMate pneumatic ventricular assist pump and a cardiotomy reservoir to
      remove air during recirculation. One empty 10 mL syringe and one 10 mL syringe
      containing 1 mL of air and 9 mL of saline were attached to a three-way stopcock.
      The air/saline bolus was then agitated between the two syringes five times to
      create bubbles and injected into the tubing proximal to the HeartMate. An EDAC
      bubble detector sensor was attached prior to the saline injection site and distal
      to the HeartMate I to measure the size and volume of the bubbles. This technique
      was repeated using 0.5 mL of air and 9.5 mL of saline bolus and 2 mL of air and 8
      mL of saline bolus. Each bolus was tested 20 times. RESULTS: This study
      identifies the potential risks of air administration and proposes a safer air
      volume to agitate for the administration of a bubble study. CONCLUSIONS: Further
      studies should be conducted to create either a guideline or a standard for
      agitated saline administration by the Intersocietal Commission for the
      Accreditation of Echocardiography Laboratories (ICAEL) in order to minimize the
      risk of air microembolism.

PMID- 24947454
TI  - Nitrogen stress response and stringent response are coupled in Escherichia coli.
AB  - Assimilation of nitrogen is an essential process in bacteria. The nitrogen
      regulation stress response is an adaptive mechanism used by nitrogen-starved
      Escherichia coli to scavenge for alternative nitrogen sources and requires the
      global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli
      cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which
      serves as an effector molecule of many processes including transcription to
      initiate global physiological changes, collectively termed the stringent
      response. The regulatory mechanisms leading to elevated ppGpp levels during
      nutritional stresses remain elusive. Here, we show that transcription of relA, a
      key gene responsible for the synthesis of ppGpp, is activated by NtrC during
      nitrogen starvation. The results reveal that NtrC couples these two major
      bacterial stress responses to manage conditions of nitrogen limitation, and
      provide novel mechanistic insights into how a specific nutritional stress leads
      to elevating ppGpp levels in bacteria. 

PMID- 24947457
TI  - Tetralogy of Fallot with pulmonary atresia and major aortopulmonary vessels.

PMID- 24947458
TI  - Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral
      vessels.
AB  - Major aortopulmonary collateral arteries (MAPCAs) provide significant issues
      during cardiopulmonary bypass, including flooding of the surgical field which
      requires significant blood volumes to be returned to the extracorporeal circuit
      via handheld suckers. This has been shown to be the major source of gaseous
      microemboli and is associated with adverse neurological outcome. Use of pH-stat
      has been previously shown to decrease the shunt through MAPCAs via an unknown
      mechanism. Here, we report the associated benefits of pH-stat in decreasing
      sucker usage and gaseous microemboli in a patient with known MAPCAs presenting
      for repair of tetralogy of Fallot and pulmonary atresia. 

PMID- 24947459
TI  - The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood
      coagulation and fluid balance: a randomized controlled trial.
AB  - INTRODUCTION: Colloids and crystalloid are used during cardiac surgery for
      priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease
      postoperative fluid balance because of their high oncotic pressure and low risk
      of fluid extravasation. On the other hand, colloids have been shown to impair
      blood coagulation. MATERIALS AND METHODS: In a prospective, randomized, double
      blinded study, 50 patients scheduled for coronary artery bypass grafting or a
      valve procedure were planned to be randomized to receive either balanced 6%
      HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped
      prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer
      groups) because of the published report where HES130/0.42 was associated with
      impaired renal function. Effects on haemostasis and fluid balance were
      investigated. RESULTS: The rotational thromboelastometry (ROTEM(r)) parameters
      and chest tube drainage on the first postoperative morning (1POM) were comparable
      between the groups (p>0.05). However, patients in the HES group needed more blood
      and blood product transfusions. The total volume administered into the CPB
      circuit was lower in the HES than in the Ringer (RIN) group, 2905+/-1049 mL
      versus 3973+/-1207 mL (p=0.011), but there was no statistically significant
      difference in total fluid balance on the 1POM (5086+/-1660 mL in the HES group
      versus 5850+/-1514 mL in the RIN group, respectively). CONCLUSIONS: After complex
      cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit
      priming did not impair haemostasis measured by ROTEM(r), but it increased the
      need for transfusions. Fluid balance after CPB was less positive in the HES
      group, but, on the 1POM, it was comparable between the groups.

PMID- 24947460
TI  - Mechanisms involved in attenuated cardio-protective role of ischemic
      preconditioning in metabolic disorders.
AB  - Myocardial infarction is a pathological state which occurs due to severe
      abrogation of the blood supply (ischemia) to a part of heart, which can cause
      myocardial damage. The short intermittent cycles of sub-lethal ischemia and
      reperfusion has shown to improve the tolerance of the myocardium against
      subsequent prolonged ischemia/reperfusion (I/R)-induced injury, which is known as
      ischemic preconditioning (IPC). Although, IPC-induced cardioprotection is well
      demonstrated in various species, including human beings, accumulated evidence
      clearly suggests critical abrogation of the beneficial effects of IPC in diabetes
      mellitus, hyperlipidemia and hyperhomocysteinemia. Various factors are involved
      in the attenuation of the cardioprotective effect of preconditioning, such as the
      reduced release of calcitonin gene-related peptide (CGRP), the over-expression of
      glycogen synthase kinase-3beta (GSK-3beta) and phosphatase and tensin homolog
      (PTEN), impairment of mito-KATP channels, the consequent opening of mitochondrial
      permeability transition pore (MPTP), etc. In this review, we have critically
      discussed the various signaling pathways involved in abrogated preconditioning in
      chronic diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. We have also
      focused on the involvement of PTEN in abrogated preconditioning and the
      significance of PTEN inhibitors. 

PMID- 24947461
TI  - Effect of vitamin D3 on behavioural and biochemical parameters in diabetes type 1
      induced rats.
AB  - Diabetes is associated with long-term complications in the brain and reduced
      cognitive ability. Vitamin D3 (VD3 ) appears to be involved in the amelioration
      of hyperglycaemia in streptozotocin (STZ)-induced diabetic rats. Our aim was to
      analyse the potential of VD3 in avoiding brain damage through evaluation of
      acetylcholinesterase (AChE), Na(+) K(+) -adenosine triphosphatase (ATPase) and
      delta aminolevulinate dehydratase (delta-ALA-D) activities and thiobarbituric
      acid reactive substance (TBARS) levels from cerebral cortex, as well as memory in
      STZ-induced diabetic rats. Animals were divided into eight groups (n = 5):
      control/saline, control/metformin (Metf), control/VD3 , control/Metf + VD3 ,
      diabetic/saline, diabetic/Metf, diabetic/VD3 and diabetic/Metf + VD3 . Thirty
      days after treatment, animals were submitted to contextual fear-conditioning and
      open-field behavioural tests, after which they were sacrificed and the cerebral
      cortex was dissected. Our results demonstrate a significant memory deficit, an
      increase in AChE activity and TBARS levels and a decrease in delta-ALA-D and
      Na(+) K(+) -ATPase activities in diabetic rats when compared with the controls.
      Treatment of diabetic rats with Metf and VD3 prevented the increase in AChE
      activity when compared with the diabetic/saline group. In treated diabetic rats,
      the decrease in Na(+) K(+) -ATPase was reverted when compared with non-treated
      rats, but the increase in delta-ALA-D activity was not. VD3 prevented diabetes
      induced TBARS level and improved memory. Our results show that VD3 can avoid
      cognitive deficit through prevention of changes in important enzymes such as
      Na(+) K(+) -ATPase and AChE in cerebral cortex in type 1 diabetic rats.

PMID- 24947463
TI  - Linkages: knowledge, decision making and election results.

PMID- 24947462
TI  - Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not
      Place-Based Navigation.
AB  - To examine the cerebellar contribution to human spatial navigation we used
      functional magnetic resonance imaging and virtual reality. Our findings show that
      the sensory-motor requirements of navigation induce activity in cerebellar
      lobules and cortical areas known to be involved in the motor loop and vestibular
      processing. By contrast, cognitive aspects of navigation mainly induce activity
      in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a
      functional link between cerebellum and hippocampus in humans and identify
      specific functional circuits linking lobule VIIA Crus I of the cerebellum to
      medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects
      of navigation. They further suggest that Crus I belongs to 2 nonmotor loops,
      involved in different strategies: place-based navigation is supported by coherent
      activity between left cerebellar lobule VIIA Crus I and medial parietal cortex
      along with right hippocampus activity, while sequence-based navigation is
      supported by coherent activity between right lobule VIIA Crus I, medial
      prefrontal cortex, and left hippocampus. These results highlight the prominent
      role of the human cerebellum in both motor and cognitive aspects of navigation,
      and specify the cortico-cerebellar circuits by which it acts depending on the
      requirements of the task. 

PMID- 24947464
TI  - Brexpiprazole II: antipsychotic-like and procognitive effects of a novel
      serotonin-dopamine activity modulator.
AB  - Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1
      yl]butoxy}quinolin-2(1H)-one) is a novel serotonin-dopamine activity modulator
      with partial agonist activity at serotonin 1A (5-HT1A) and D2/3 receptors,
      combined with potent antagonist effects on 5-HT2A, alpha1B-, and alpha2C
      adrenergic receptors. Brexpiprazole inhibited conditioned avoidance response
      (ED50 = 6.0 mg/kg), apomorphine- or d-amphetamine-induced hyperactivity (ED50 =
      2.3 and 0.90, respectively), and apomorphine-induced stereotypy (ED50 = 2.9) in
      rats at clinically relevant D2 receptor occupancies. Brexpiprazole also potently
      inhibited apomorphine-induced eye blinking in monkeys. The results suggest that
      brexpiprazole has antipsychotic potential. Brexpiprazole induced catalepsy (ED50
      = 20) well above clinically relevant D2 receptor occupancies, suggesting a low
      risk for extrapyramidal side effects. Subchronic treatment with phencyclidine
      (PCP) induced cognitive impairment in both novel object recognition (NOR) and
      attentional set-shifting (ID-ED) tests in rats. Brexpiprazole reversed the PCP
      induced cognitive impairment in the NOR test at 1.0 and 3.0 mg/kg, and in the ID
      ED test at 1.0 mg/kg. However, aripiprazole (10 mg/kg) was ineffective in both
      tests, despite achieving relevant D2 occupancies. In the NOR test, the 5-HT1A
      agonist buspirone and the 5-HT2A antagonist M100907 [(R)-(2,3-dimethoxyphenyl)[1
      (4-fluorophenethyl)piperidin-4-yl]methanol] partially but significantly reversed
      PCP-induced impairment. Furthermore, the effect of brexpiprazole was reversed by
      cotreatment with the 5-HT1A antagonist WAY100635 (N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate). The results
      indicate that brexpiprazole has antipsychotic-like activity and robust efficacy
      in relevant models of cognitive impairment associated with schizophrenia. The
      effects of brexpiprazole in the cognitive tests are superior to those of
      aripiprazole. We propose that the pharmacologic profile of brexpiprazole be based
      on its balanced effects on 5-HT1A, D2, and 5-HT2A receptors, with possible
      modulating activity through additional monoamine receptors. 

PMID- 24947465
TI  - Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin
      dopamine activity modulator.
AB  - Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1
      yl]butoxy}quinolin-2(1H)-one) is a novel drug candidate in clinical development
      for psychiatric disorders with high affinity for serotonin, dopamine, and
      noradrenaline receptors. In particular, it bound with high affinity (Ki < 1 nM)
      to human serotonin 1A (h5-HT1A)-, h5-HT2A-, long form of human D2 (hD2L)-,
      halpha1B-, and halpha2C-adrenergic receptors. It displayed partial agonism at h5
      HT1A and hD2 receptors in cloned receptor systems and potent antagonism of h5
      HT2A receptors and halpha1B/2C-adrenoceptors. Brexpiprazole also had affinity (Ki
      < 5 nM) for hD3-, h5-HT2B-, h5-HT7-, halpha1A-, and halpha1D-adrenergic
      receptors, moderate affinity for hH1 (Ki = 19 nM), and low affinity for hM1
      receptors (Ki > 1000 nM). Brexpiprazole potently bound to rat 5-HT2A and D2
      receptors in vivo, and ex vivo binding studies further confirmed high 5-HT1A
      receptor binding potency. Brexpiprazole inhibited DOI (2,5-dimethoxy-4
      iodoamphetamine)-induced head twitches in rats, suggestive of 5-HT2A antagonism.
      Furthermore, in vivo D2 partial agonist activity of brexpiprazole was confirmed
      by its inhibitory effect on reserpine-induced DOPA accumulation in rats. In rat
      microdialysis studies, brexpiprazole slightly reduced extracellular dopamine in
      nucleus accumbens but not in prefrontal cortex, whereas moderate increases of the
      dopamine metabolites, homovanillic acid and DOPAC (3,4-dihydroxy-phenyl-acetic
      acid), in these areas also suggested in vivo D2 partial agonist activity. In
      particular, based on a lower intrinsic activity at D2 receptors and higher
      binding affinities for 5-HT1A/2A receptors than aripiprazole, brexpiprazole would
      have a favorable antipsychotic potential without D2 receptor agonist- and
      antagonist-related adverse effects. In conclusion, brexpiprazole is a serotonin
      dopamine activity modulator with a unique pharmacology, which may offer novel
      treatment options across a broad spectrum of central nervous system disorders. 

PMID- 24947467
TI  - Blood-brain barrier pharmacoproteomics-based reconstruction of the in vivo brain
      distribution of P-glycoprotein substrates in cynomolgus monkeys.
AB  - The aim of this study was to investigate whether in vivo drug distribution in
      brain in monkeys can be reconstructed by integrating four factors: protein
      expression levels of P-glycoprotein (P-gp)/multidrug resistance protein 1 at the
      blood-brain barrier (BBB), in vitro transport activity per P-gp molecule, and
      unbound drug fractions in plasma and brain. For five P-gp substrates (indinavir,
      quinidine, loperamide, paclitaxel, and verapamil) and one nonsubstrate
      (diazepam), in vitro P-gp transport activities were determined by measuring
      transcellular transport across monolayers of cynomolgus monkey P-gp-transfected
      LLC-PK1 and parental cells. In vivo P-gp functions at the BBB were reconstructed
      from in vitro P-gp transport activities and P-gp expression levels in transfected
      cells and cynomolgus brain microvessels. Brain-to-plasma concentration ratios
      (Kp,brain) were reconstructed by integrating the reconstructed in vivo P-gp
      functions with drug unbound fractions in plasma and brain. For all compounds, the
      reconstructed Kp,brain values were within a 3-fold range of observed values, as
      determined by constant intravenous infusion in adult cynomolgus monkeys. Among
      four factors, plasma unbound fraction was the most sensitive factor to species
      differences in Kp,brain between monkeys and mice. Unbound brain-to-plasma
      concentration ratios (Kp,uu,brain) were reconstructed as the reciprocal of the
      reconstructed in vivo P-gp functions, and the reconstructed Kp,uu,brain values
      were within a 3-fold range of in vivo values, which were estimated from observed
      Kp,brain and unbound fractions. This study experimentally demonstrates that brain
      distributions of P-gp substrates and nonsubstrate can be reconstructed on the
      basis of pharmacoproteomic concept in monkeys, which serve as a robust model of
      drug distribution in human brain. 

PMID- 24947466
TI  - Characterization of the novel positive allosteric modulator of the metabotropic
      glutamate receptor 4 ADX88178 in rodent models of neuropsychiatric disorders.
AB  - There is growing evidence that activation of metabotropic glutamate receptor 4
      (mGlu4) leads to anxiolytic- and antipsychotic-like efficacy in rodent models,
      yet its relevance to depression-like reactivity remains unclear. Here, we present
      the pharmacological evaluation of ADX88178 [5-methyl-N-(4-methylpyrimidin-2-yl)-4
      (1H-pyrazol-4-yl)thiazol-2-amine], a novel potent, selective, and brain-penetrant
      positive allosteric modulator of the mGlu4 receptor in rodent models of anxiety,
      obsessive compulsive disorder (OCD), fear, depression, and psychosis. ADX88178
      dose-dependently reduced the number of buried marbles in the marble burying test
      and increased open-arm exploration in the elevated plus maze (EPM) test,
      indicative of anxiolytic-like efficacy. Target specificity of the effect in the
      EPM test was confirmed using male and female mGlu4 receptor knockout mice. In
      mice, ADX88178 reduced the likelihood of conditioned freezing in the acquisition
      phase of the fear conditioning test, yet had no carryover effect in the
      expression phase. Also, ADX88178 dose-dependently reduced duration of immobility
      in the forced swim test, indicative of antidepressant-like efficacy. ADX88178
      reduced DOI (2,5-dimethoxy-4-iodoamphetamine)-mediated head twitches (albeit with
      no dose-dependency), and MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine]-induced locomotor hyperactivity in mice, but
      was inactive in the conditioned avoidance response test in rats. The compound
      showed good specificity as it had no effect on locomotor activity in mice and
      rats at efficacious doses. Thus, allosteric activation of mGlu4 receptors can be
      a promising new therapeutic approach for treatment of anxiety, OCD, fear-related
      disorders, and psychosis. 

PMID- 24947468
TI  - A systematic review of the clinical effectiveness and cost-effectiveness of
      sensory, psychological and behavioural interventions for managing agitation in
      older adults with dementia.
AB  - BACKGROUND: Agitation is common, persistent and distressing in dementia and is
      linked with care breakdown. Psychotropic medication is often ineffective or
      harmful, but the evidence regarding non-pharmacological interventions is unclear.
      OBJECTIVES: We systematically reviewed and synthesised the evidence for clinical
      effectiveness and cost-effectiveness of non-pharmacological interventions for
      reducing agitation in dementia, considering dementia severity, the setting, the
      person with whom the intervention is implemented, whether the effects are
      immediate or longer term, and cost-effectiveness. DATA SOURCES: We searched twice
      using relevant search terms (9 August 2011 and 12 June 2012) in Web of Knowledge
      (incorporating MEDLINE); EMBASE; British Nursing Index; the Health Technology
      Assessment programme database; PsycINFO; NHS Evidence; System for Information on
      Grey Literature; The Stationery Office Official Documents website; The Stationery
      National Technical Information Service; Cumulative Index to Nursing and Allied
      Health Literature; and The Cochrane Library. We also searched Cochrane reviews of
      interventions for behaviour in dementia, included papers' references, and
      contacted authors about 'missed' studies. We included quantitative studies,
      evaluating non-pharmacological interventions for agitation in dementia, in all
      settings. REVIEW METHOD: We rated quality, prioritising higher-quality studies.
      We separated results by intervention type and agitation level. As we were unable
      to meta-analyse results except for light therapy, we present a qualitative
      evidence synthesis. In addition, we calculated standardised effect sizes (SESs)
      with available data, to compare heterogeneous interventions. In the health
      economic analysis, we reviewed economic studies, calculated the cost of effective
      interventions from the effectiveness review, calculated the incremental cost per
      unit improvement in agitation, used data from a cohort study to evaluate the
      relationship between health and social care costs and health-related quality of
      life (DEMQOL-Proxy-U scores) and developed a new cost-effectiveness model.
      RESULTS: We included 160 out of 1916 papers screened. Supervised person-centred
      care, communication skills (SES = -1.8 to -0.3) or modified dementia care mapping
      (DCM) with implementing plans (SES = -1.4 to -0.6) were all efficacious at
      reducing clinically significant agitation in care home residents, both
      immediately and up to 6 months afterwards. In care home residents, during
      interventions but not at follow-up, activities (SES = -0.8 to -0.6) and music
      therapy (SES = -0.8 to -0.5) by protocol reduced mean levels of agitation;
      sensory intervention (SES = -1.3 to -0.6) reduced mean and clinically significant
      symptoms. Advantages were not demonstrated with 'therapeutic touch' or
      individualised activity. Aromatherapy and light therapy did not show clinical
      effectiveness. Training family carers in behavioural or cognitive interventions
      did not decrease severe agitation. The few studies reporting activities of daily
      living or quality-of-life outcomes found no improvement, even when agitation had
      improved. We identified two health economic studies. Costs of interventions which
      significantly impacted on agitation were activities, L80-696; music therapy, L13
      27; sensory interventions, L3-527; and training paid caregivers in person-centred
      care or communication skills with or without behavioural management training and
      DCM, L31-339. Among the 11 interventions that were evaluated using the Cohen
      Mansfield Agitation Inventory (CMAI), the incremental cost per unit reduction in
      CMAI score ranged from L162 to L3480 for activities, L4 for music therapy, L24 to
      L143 for sensory interventions, and L6 to L62 for training paid caregivers in
      person-centred care or communication skills with or without behavioural
      management training and DCM. Health and social care costs ranged from around
      L7000 over 3 months in people without clinically significant agitation symptoms
      to around L15,000 at the most severe agitation levels. There is some evidence
      that DEMQOL-Proxy-U scores decline with Neuropsychiatric Inventory agitation
      scores. A multicomponent intervention in participants with mild to moderate
      dementia had a positive monetary net benefit and a 82.2% probability of being
      cost-effective at a maximum willingness to pay for a quality-adjusted life-year
      of L20,000 and a 83.18% probability at a value of L30,000. LIMITATIONS: Although
      there were some high-quality studies, there were only 33 reasonably sized (> 45
      participants) randomised controlled trials, and lack of evidence means that we
      cannot comment on many interventions' effectiveness. There were no hospital
      studies and few studies in people's homes. More health economic data are needed.
      CONCLUSIONS: Person-centred care, communication skills and DCM (all with
      supervision), sensory therapy activities, and structured music therapies reduce
      agitation in care-home dementia residents. Future interventions should change
      care home culture through staff training and permanently implement evidence-based
      treatments and evaluate health economics. There is a need for further work on
      interventions for agitation in people with dementia living in their own homes.
      PROTOCOL REGISTRATION: The study was registered as PROSPERO no. CRD42011001370.
      FUNDING: The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 24947470
TI  - Synthesis of monolayer platinum nanosheets.
AB  - Platinum (Pt) nanosheets were developed by exfoliating layered platinum oxide.
      Moreover, we succeeded in synthesizing monolayer Pt nanosheets for the first time
      by adjusting the conditions for reduction. Monolayer Pt nanosheets were highly
      active in oxygen reduction reaction. 

PMID- 24947471
TI  - How TOPO affects the interface of the novel mixed water/AOT:TOPO/n-heptane
      reverse micelles: dynamic light scattering and Fourier transform infrared
      spectroscopy studies.
AB  - In this work we report for the first time the formation of two reverse micelle
      (RM) media produced by the nonionic surfactant tri-n-octyl phosphine oxide (TOPO)
      in n-heptane and the one produced by mixing the anionic sodium 1,4-bis-2
      ethylhexylsulfosuccinate (AOT) with different TOPO contents dissolved in n
      heptane. Dynamic light scattering (DLS) experiments reveal the formation of
      water/TOPO/n-heptane RMs (TOPO RMs) and water/AOT:TOPO/n-heptane RMs (mixed RMs)
      since the droplet sizes increase as the water content increases. The addition of
      TOPO to the system at constant W0 (W0 = [water]/([AOT] + [TOPO])) causes the
      droplet sizes of mixed RMs to decrease compared with the AOT RMs. In addition,
      the decrease is larger when the water content is low (W0 = 0.5) but the effect is
      negligible at the maximum W0 value analyzed (W0 = 2). These results are not
      expected for mixtures of different nonionic surfactants with AOT and were
      explained considering the unique TOPO structure. Thus, at W0 = 0.5, we suggest
      that the percentage of TOPO molecules at the mixed RM interface is higher than
      those corresponding to the bulk solution. On the other hand, at W0 = 2 the RM
      interface is comprised mainly of AOT molecules. The FT-IR experiments performed
      by monitoring monodeuterated water frequency (nu(OD)) in TOPO RMs show bound and
      "bulk-like" water structure even at very low water content. On the other hand,
      for mixed RMs the water structure depends on the water content. At low W0 value,
      there are two kinds of water molecules, and at W0 value around 2 only bound water
      exists. The Fourier transform infrared (FT-IR) experiments performed on the
      symmetric (nu(s)SO3) and asymmetric (nu(a)SO3) sulfonate stretching bands of AOT
      reveal the existence of a strong Na(+)TOPO complex in the mixed RMs. The results
      show that adding TOPO to form mixed surfactant RMs with AOT reduces their size,
      changes the nature of water to have a "bulk-like" character and diminishes the
      ion pairing of the sulfonate group with Na(+).

PMID- 24947469
TI  - Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on
      the mother centriole during cilia biogenesis.
AB  - The primary cilium originates from the mother centriole and participates in
      critical functions during organogenesis. Defects in cilia biogenesis or function
      lead to pleiotropic phenotypes. Mutations in centrosome-cilia gene CC2D2A result
      in Meckel and Joubert syndromes. Here we generate a Cc2d2a(-/-) mouse that
      recapitulates features of Meckel syndrome including embryonic lethality and
      multiorgan defects. Cilia are absent in Cc2d2a(-/-) embryonic node and other
      somatic tissues; disruption of cilia-dependent Shh signalling appears to underlie
      exencephaly in mutant embryos. The Cc2d2a(-/-) mouse embryonic fibroblasts (MEFs)
      lack cilia, although mother centrioles and pericentriolar proteins are detected.
      Odf2, associated with subdistal appendages, is absent and ninein is reduced in
      mutant MEFs. In Cc2d2a(-/-) MEFs, subdistal appendages are lacking or abnormal by
      transmission electron microscopy. Consistent with this, CC2D2A localizes to
      subdistal appendages by immuno-EM in wild-type cells. We conclude that CC2D2A is
      essential for the assembly of subdistal appendages, which anchor cytoplasmic
      microtubules and prime the mother centriole for axoneme biogenesis. 

PMID- 24947473
TI  - Are nurse injectors the new norm?
AB  - PURPOSE: As Botox((r))/filler use has increased in recent years, a growing number
      of nonaesthetic health professionals have emerged to perform these procedures.
      Since studies have shown that patients identify training as the most important
      factor in considering these procedures, this study seeks to summarize the
      perspective of plastic surgeons regarding these paradigm shifts. METHODS: In the
      summer of 2013, an eight-question survey was sent to members of ISAPS, ASAPS, and
      ASPS (approximately 26,113 plastic surgeons globally). Two questions assessed
      practice location and membership affiliation and six questions assessed various
      healthcare practitioners' capability to administer Botox, fillers, and vaccines
      (control). Healthcare practitioners included plastic surgeons and dermatologists,
      gynecologists, dentists, nurses in plastic surgery and dermatology, or nurses in
      other fields. RESULTS: On three e-mail notifications, 14,184 plastic surgeons
      opened the survey and 882 responded: 36.6 % from North America, 29.1 % from
      Europe, 12.9 % from South America, 10.1 % from Asia, 4.5 % from the Middle East,
      3.4 % from Australia, 1.9 % from Africa, and 1.6 % from Central America. Seventy
      seven percent believed nurses were not as capable as plastic surgeons in
      administering Botox; 81 % felt the same for fillers. Conversely, 84 % agreed that
      nurses were as capable as plastic surgeons in administering vaccines. Plastic
      surgeons ranked nurses in other fields (48 %) as most capable in administering
      vaccines, then plastic surgeons (42 %), nurses of plastic surgeons (9 %),
      gynecologists (1 %), and dentists (<1 %). When asked about Botox/fillers,
      responders ranked plastic surgeons (98 %) most capable, then nurses in plastic
      surgery (2 %), gynecologists (<1 %), dentists (<1 %), and nurses in other fields
      (<1 %). When asked to rank according to patient perception, the order remained
      the same. CONCLUSION: Based on responses from over 880 plastic surgeons from
      around the world, plastic surgeons consider themselves and dermatologists the
      most capable injectors. However, they still believe nurses in other fields to be
      the most capable of administering vaccines. This dichotomy may define the role of
      various practitioners in an increasingly more competitive injectable environment
      to improve patient satisfaction and outcomes. Given that the majority of growth
      in cosmetic injectables is being driven by providers other than plastic surgeons
      and dermatologists, further clarification on training requirements and practice
      guidelines may be necessary to ensure a consistent, reproducible experience for
      the patient.

PMID- 24947472
TI  - Apical dominance in saffron and the involvement of the branching enzymes CCD7 and
      CCD8 in the control of bud sprouting.
AB  - BACKGROUND: In saffron (Crocus sativus), new corms develop at the base of every
      shoot developed from the maternal corm, a globular underground storage stem.
      Since the degree of bud sprouts influences the number and size of new corms, and
      strigolactones (SLs) suppress growth of pre-formed axillary bud, it was
      considered appropriate to investigate SL involvement in physiology and molecular
      biology in saffron. We focused on two of the genes within the SL pathway, CCD7
      and CCD8, encoding carotenoid cleavage enzymes required for the production of
      SLs. RESULTS: The CsCCD7 and CsCCD8 genes are the first ones isolated and
      characterized from a non-grass monocotyledonous plant. CsCCD7 and CsCCD8
      expression showed some overlapping, although they were not identical. CsCCD8 was
      highly expressed in quiescent axillary buds and decapitation dramatically reduced
      its expression levels, suggesting its involvement in the suppression of axillary
      bud outgrowth. Furthermore, in vitro experiments showed also the involvement of
      auxin, cytokinin and jasmonic acid on the sprouting of axillary buds from corms
      in which the apical bud was removed. In addition, CsCCD8 expression, but not
      CsCCD7, was higher in the newly developed vascular tissue of axillary buds
      compared to the vascular tissue of the apical bud. CONCLUSIONS: We showed that
      production and transport of auxin in saffron corms could act synergistically with
      SLs to arrest the outgrowth of the axillary buds, similar to the control of above
      ground shoot branching. In addition, jasmonic acid seems to play a prominent role
      in bud dormancy in saffron. While cytokinins from roots promote bud outgrowth. In
      addition the expression results of CsCCD8 suggest that SLs could positively
      regulate procambial activity and the development of new vascular tissues
      connecting leaves with the mother corm.

PMID- 24947474
TI  - PD2/Paf1 depletion in pancreatic acinar cells promotes acinar-to-ductal
      metaplasia.
AB  - Pancreatic differentiation 2 (PD2), a PAF (RNA Polymerase II Associated Factor)
      complex subunit, is overexpressed in pancreatic cancer cells and has demonstrated
      potential oncogenic property. Here, we report that PD2/Paf1 expression was
      restricted to acinar cells in the normal murine pancreas, but its expression
      increased in the ductal cells of KrasG12D/Pdx1Cre (KC) mouse model of pancreatic
      cancer with increasing age, showing highest expression in neoplastic ductal cells
      of 50 weeks old mice. PD2/Paf1 was specifically expressed in amylase and CK19
      double positive metaplastic ducts, representing intermediate structures during
      pancreatic acinar-to-ductal metaplasia (ADM). Similar PD2/Paf1 expression was
      observed in murine pancreas that exhibited ADM-like histology upon cerulein
      challenge. In normal mice, cerulein-mediated inflammation induced a decrease in
      PD2/Paf1 expression, which was later restored upon recovery of the pancreatic
      parenchyma. In KC mice, however, PD2/Paf1 mRNA level continued to decrease with
      progressive dysplasia and subsequent neoplastic transformation. Additionally,
      knockdown of PD2/Paf1 in pancreatic acinar cells resulted in the abrogation of
      Amylase, Elastase and Lipase (acinar marker) mRNA levels with simultaneous
      increase in CK19 and CAII (ductal marker) transcripts. In conclusion, our studies
      indicate loss of PD2/Paf1 expression during acinar transdifferentiation in
      pancreatic cancer initiation and PD2/Paf1 mediated regulation of lineage specific
      markers. 

PMID- 24947476
TI  - Predictors and outcomes of community agency use in abused mothers.
AB  - OBJECTIVE: To identify characteristics of abused mothers that predict use and
      difficulty of use of community agencies for intimate partner violence (IPV) and
      to describe the outcomes of community agency use. DESIGN AND SAMPLE: A
      prospective study design was used. Three hundred mothers who had experienced
      physical or sexual IPV and were seeking services for the first time at either a
      safe shelter for abused women or applying for a protection order. MEASURES: Data
      were collected and analyzed by the research team. Predictors were tested using
      binary logistic regression and outcomes were tested using a series of Mann
      Whitney U nonparametric test of difference on change scores between baseline and
      24-month scores. RESULTS: No individual predictors were statistically significant
      and/or meaningful for use or difficulty using community agencies. There were
      significant differences in change scores for severity of violence after women
      used counseling, the police, or legal services. There were also significant
      change scores for anxiety after women used legal services and social services.
      CONCLUSIONS: Abused women need individualized attention to assure that they can
      access the services they need to recover from IPV. Evidence-based practice is
      needed for community agencies to treat abused women to facilitate safety and
      health.

PMID- 24947478
TI  - Giant axonal neuropathy: An updated perspective on its pathology and
      pathogenesis.
AB  - Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It
      is best known for the "giant" axons caused by accumulations of intermediate
      filaments. The disease is progressive, with onset around age 3 years and death by
      the third decade of life. GAN results from recessive mutations in the GAN gene
      encoding gigaxonin, and our analysis of all reported mutations shows that they
      are distributed throughout the protein structure. Precisely how these mutations
      cause the disease remains to be determined. In addition to changes in peripheral
      nerves that are similar to those seen in neuropathies such as Charcot-Marie-Tooth
      type 2, GAN patients exhibit a wide range of central nervous system signs. These
      features, corroborated by degeneration of central tracts apparent from postmortem
      pathology, indicate that GAN is also a progressive neurodegenerative disease. To
      reflect this phenotype more precisely, we therefore propose that the disease
      should be more appropriately referred to as "giant axonal neurodegeneration."

PMID- 24947477
TI  - Predictors for an unsuccessful INtubation-SURfactant-Extubation procedure: a
      cohort study.
AB  - BACKGROUND: The INtubation-SURfactant-Extubation (INSURE) is a procedure that is
      increasingly being used to treat the respiratory distress syndrome in preterm
      infants. The objective of this study was to identify predictors for an
      unsuccessful INSURE procedure. METHODS: The neonates included were less than 32
      weeks' gestation, treated with surfactant in the neonatal intensive care unit,
      and born 1998-2010. INSURE was defined as surfactant administration during
      intubation for less than 2 hours without the need for mechanical ventilation.
      INSURE success was defined as no re-intubation within 72 hours after INSURE, and
      INSURE failure was defined as re-intubation within 72 hours after INSURE. An
      unsuccessful INSURE procedure was either INSURE failure or mechanical ventilation
      for more than 24 hours immediately after surfactant administration. All
      predictors were defined a priori and were present before surfactant
      administration. Multivariate logistic regression was performed. RESULTS: In
      total, 322 neonates were included: 31% (n = 100) had INSURE success, 10% (n = 33)
      had INSURE failure, 49% (n = 158) needed mechanical ventilation for more than 24
      hours, and the remaining 10% (n = 31) needed mechanical ventilation for less than
      24 hours. Predictors for INSURE failure were low gestational age and hemoglobin
      below 8.5 mmol/l. Predictors for mechanical ventilation for more than 24 hours
      were low gestational age, Apgar at 5 minutes below 7, oxygen need above 50%, CO2
      pressure above 7 kPa (~53 mmHg), pH below 7.3, lactate above 2.5 mmol/l, need for
      inotropes, and surfactant administration shortly after birth, whereas
      preeclampsia reduced the risk. CONCLUSIONS: We identified specific predictors
      associated with an unsuccessful INSURE procedure. Keeping high-risk neonates with
      one or several predictors intubated and treated with mechanical ventilation after
      surfactant may prevent a re-intubation procedure.

PMID- 24947479
TI  - DNA binders in clinical trials and chemotherapy.
AB  - Cancer has always been a dreadful disease and continues to attract extensive
      research investigations. Various targets have been identified to restrain cancer.
      Among these DNA happens to be the most explored one. A wide variety of small
      molecules, often referred to as 'ligands', has been synthesized to target
      numerous structural features of DNA. The sole purpose of such molecular design
      has been to interfere with the transcriptional machinery in order to drive the
      cancer cell toward apoptosis. The mode of action of the DNA targeting ligands
      focuses either on the sequence-specificity by groove binding and strand cleavage,
      or by identifying the morphologically distinct higher order structures like that
      of the G-quadruplex DNA. However, in spite of the extensive research, only a tiny
      fraction of the molecules have been able to reach clinical trials and only a
      handful are used in chemotherapy. This review attempts to record the journey of
      the DNA binding small molecules from its inception to cancer therapy via various
      modifications at the molecular level. Nevertheless, factors like limited
      bioavailability, severe toxicities, unfavorable pharmacokinetics etc. still prove
      to be the major impediments in the field which warrant considerable scope for
      further research investigations. 

PMID- 24947475
TI  - Comparative intrauterine development and placental function of ART concepti:
      implications for human reproductive medicine and animal breeding.
AB  - BACKGROUND: The number of children conceived using assisted reproductive
      technologies (ART) has reached >5 million worldwide and continues to increase.
      Although the great majority of ART children are healthy, many reports suggest a
      forthcoming risk of metabolic complications, which is further supported by the
      Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal
      conditions predisposing adult cardiometabolic pathologies. Accumulating evidence
      suggests that fetal and placental growth kinetics are important features
      predicting post-natal health, but the relationship between ART and intrauterine
      growth has not been systematically reviewed. METHODS: Relevant studies describing
      fetoplacental intrauterine phenotypes of concepti generated by in vitro
      fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell
      nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively
      researched using PubMed and Google Scholar. Intrauterine growth plots were
      created from tabular formatted data available in selected reports. RESULTS: ART
      pregnancies display minor but noticeable alterations in fetal and placental
      growth curves across mammalian species. In all species, there is evidence of
      fetal growth restriction in the earlier stages of pregnancy, followed by
      significant increases in placental size and accelerated fetal growth toward the
      end of gestation. However, there is a species-specific effect of ART on
      birthweights, that additionally vary in a culture condition-, strain-, and/or
      stage at transfer-specific manner. We discuss the potential mechanisms that
      underlie these changes, and how they are affected by specific components of ART
      procedures. CONCLUSIONS: ART may promote measurable alterations to intrauterine
      growth trajectory and placental function. Key findings include evidence that
      birthweight is not a reliable marker of fetal stress, and that increases in
      embryo manipulation result in more deviant fetal growth curves. Because growth
      kinetics in early life are particularly relevant to adult metabolic physiology,
      we advise more rigorous assessment of fetal growth and placental function in
      human ART pregnancies, as well as continued follow-up of ART offspring throughout
      post-natal life. Finally, strategies to minimize embryo manipulations should be
      adopted whenever possible.

PMID- 24947480
TI  - Polymer supported synthesis of a natural product-inspired oxepane library.
AB  - Natural product inspired compound collections are prevalidated due to the
      evolutionary selection of the natural product scaffolds. Their synthesis requires
      the development of novel strategies amenable to formats suitable for library
      build-up. We describe a method for the synthesis of an oxepane library inspired
      by the core structure of oxepane natural products endowed with multiple
      bioactivities. Core aspects of the strategy are the establishment of a one-pot
      method employing different immobilized scavengers, the employment of an enyne
      ring closing reaction and diversification by means of different transformations,
      for example, cycloadditions and cross-metathesis reactions. In total, a
      collection of 115 oxepanes was obtained in 5-6-step reaction sequences. 

PMID- 24947481
TI  - Finding a human telomere DNA-RNA hybrid G-quadruplex formed by human telomeric 6
      mer RNA and 16-mer DNA using click chemistry: a protective structure for telomere
      end.
AB  - Telomeric repeat-containing RNA is a non-coding RNA molecule newly found in
      mammalian cells. The telomere RNA has been found to localize to the telomere DNA,
      but how the newly discovered RNA molecule interacts with telomere DNA is less
      known. In this study, using the click chemistry we successfully found that a 6
      mer human telomere RNA and 16-mer human telomere DNA sequence can form a DNA-RNA
      hybrid type G-quadruplex structure. Detection of the click-reaction products
      directly probes DNA-RNA G-quadruplex structures in a complicated solution,
      whereas traditional methods such as NMR and crystallography may not be suitable.
      Importantly, we found that formation of DNA-RNA G-quadruplex induced an
      exonuclease resistance for telomere DNA, indicating that such structures might be
      important for protecting telomeric DNA from enzyme digestion to avoid telomere
      DNA shortening. These results provide the direct evidence for formation of DNA
      RNA hybrid G-quadruplex structure by human telomere DNA and RNA sequence,
      suggesting DNA-RNA hybrid G-quadruplex structure associated between telomere DNA
      and RNA may respond to chromosome end protection and/or present a valuable target
      for drug design. 

PMID- 24947482
TI  - Mycobacterium tuberculosis treatment modalities and recent insights.
AB  - Antimicrobial therapy of infections caused by M. tuberculosis is a challenge due
      to poor response to therapy and recurrent infections. Under in vitro conditions,
      antibiotics effectively kill M. tuberculosis within the first two weeks. However,
      an extended treatment time of 6-9 months is required to eradicate M. tuberculosis
      infection, mainly due to the intracellular survival of this pathogen and poor
      penetration of the antibiotics into the intracellular compartment of the host
      cells. Recent advances in the field of drug delivery have led to the use of
      different antibiotic incorporated nano- and micro- formulations such as
      liposomes, polymeric particles, mesoporous silica particles and particulate
      suspensions for targeted drug delivery applications into the intracellular
      compartment of the macrophages. The drug incorporated nano- and micro-particles
      are prone to be easily internalized, which leads to preferential delivery of the
      drugs into the tissues and organs of interest. Other advantages of these nano-
      and micro-particles over the free drugs are their comparatively higher stability
      and bioavailability. This review highlights the current strategies and challenges
      in treatment, the different antibiotics available, their modes of action,
      generation and mechanism of drug resistance and recent advances in the
      intracellular drug delivery using nanoparticles for the treatment of
      tuberculosis. 

PMID- 24947483
TI  - Uterine infusion with bone marrow mesenchymal stem cells improves endometrium
      thickness in a rat model of thin endometrium.
AB  - Bone marrow mesenchymal stem cells (BMSCs) show multidirectional differentiation
      and possess immunoregulatory properties. Although transplantation of BMSCs has a
      therapeutic effect on many diseases, it is unclear whether BMSC transplantation
      can be used as a therapy for a thin endometrium. To explore whether
      transplantation of BMSCs directly into the uterine cavity can improve endometrium
      thickness, a thin endometrium rat model was established by infusing ethanol into
      the uterine cavity. In all, 48 rats with thin endometrium and 24 normal rats were
      divided into 3 groups: (1) normal group, (2) experimental group transplanted with
      BMSCs into uterine cavity, and (3) control group transplanted with saline into
      the uterine cavity. The morphology of the endometrium, the regeneration and
      receptivity of the endometrium, and the mechanisms involved in BMSC therapy were
      subsequently analyzed by hematoxylin and eosin staining, Western blot analysis,
      and reverse transcription-polymerase chain reaction throughout an observation
      period of 3 estrus cycles. The rats in the experimental group had a significantly
      thicker endometrial lining and exhibited higher expression of cytokeratin,
      vimentin, integrin alphagammabeta3, and leukaemia inhibitor factor (LIF) than
      that of the control group (P < .05). Bromodeoxyuridine -positive cells were
      detected in the endometrium after BMSC transplantation. Some proinflammatory
      cytokines, such as tumor necrosis factor alpha messenger RNA (mRNA) and
      interleukin (IL)-1betamRNA, were significantly downregulated, and anti
      inflammatory cytokines, such as basic fibroblast growth factor (bFGF) mRNA and IL
      6mRNA, were significantly upregulated in the experimental group compared to the
      control group (P < .05). In conclusion, BMSCs improved endometrium thickness,
      probably via their migration and immunomodulatory properties. Uterine perfusion
      with BMSCs represents a promising new tool for the currently intractable problem
      of an inadequate, thin endometrium. 

PMID- 24947484
TI  - First trimester coffee and tea intake and risk of gestational diabetes mellitus:
      a study within a national birth cohort.
AB  - OBJECTIVE: Coffee and tea consumption is associated with a decreased type 2
      diabetes risk in non-pregnant adults. We examined the relation between first
      trimester coffee and tea consumption and gestational diabetes mellitus (GDM)
      risk. DESIGN: Population-based cohort study. SETTING: Denmark 1996-2002.
      POPULATION: Non-diabetic women with singleton pregnancies in the Danish National
      Birth Cohort (n = 71,239). METHODS: Estimated adjusted relative risks (RR) and
      95% confidence intervals (95%CI) for the association between first trimester
      coffee and tea or estimated total caffeine and GDM. MAIN OUTCOME MEASURES: GDM
      ascertained from the National Hospital Discharge Register or maternal interview.
      RESULTS: Coffee or tea intake was reported in 81.2% (n = 57,882) and 1.3% (n =
      912) of pregnancies were complicated by GDM. Among non-consumers, 1.5% of
      pregnancies were complicated by GDM. Among coffee drinkers, GDM was highest among
      women who drank >=8 cups/day (1.8%) with no significant difference across intake
      levels (P = 0.10). Among tea drinkers, there was no difference in GDM across
      intake levels (1.2%; P = 0.98). After adjustment for age, socio-occupational
      status, parity, pre-pregnancy body mass index, smoking, and cola, there was
      suggestion of a protective, but non-significant association with increasing
      coffee (RR >=8 versus 0 cups/day = 0.89 [95%CI 0.64-1.25]) and tea (RR >=8 versus
      0 cups/day = 0.77 [95%CI 0.55-1.08]). Results were similar by smoking status,
      except a non-significant 1.45-fold increased risk with >=8 coffee cups/day for
      non-smokers. There was a non-significant reduced GDM risk with increasing total
      caffeine. CONCLUSIONS: Our results suggest that moderate first trimester coffee
      and tea intake were not associated with GDM increased risk and possibly may have
      a protective effect.

PMID- 24947486
TI  - [A national framework for educational programs in epileptic patients, children
      and adults].
AB  - Epilepsy is a chronic disease with a wide range of presentations occurring at any
      age. It affects the patient's quality of life, implying a need for numerous
      healthcare services. Therapeutic education programs (TEPs) are designed to match
      patient age, disease course, and individual learning abilities. In France, these
      programs are proposed by the national health authorities (Superior Health
      Authority), and authorized by the Regional Health Agencies. Two years ago, a
      Therapeutic Education Programs Commission (TEPC), supported by the French League
      against Epilepsy (FLAE), was created. The goal was to bring together
      representative healthcare professionals in a working group in order to
      standardize practices. This led to the creation of a national reference of
      healthcare skills specific for children and adults with epilepsy. Five tables,
      for five "life periods", outline the framework of this professional reference
      tool. Program personalization, an essential part of TEPs, is necessary to develop
      a creative atmosphere. This slow process is specific to the various stages of
      life and can be influenced by the occurrence of various handicaps. Family and
      caregivers make key contributions to the process. The national framework for
      therapeutic education in epilepsy serves as a central crossroad where professions
      can find essential information to create or adapt their own TEPs. In the near
      future, regional experiences will be documented and collected for regular
      updates. This professional therapeutic education network will help promote
      therapeutic education programs and facilitate standard practices. Finally,
      several TEP files and tools will be shared on the FLAE website available for
      professional access. Today, the group's goal is to achieve national deployment of
      this "referential" framework.

PMID- 24947485
TI  - Nucleotide polymorphism and copy number variant detection using exome capture and
      next-generation sequencing in the polyploid grass Panicum virgatum.
AB  - Switchgrass (Panicum virgatum) is a polyploid, outcrossing grass species native
      to North America and has recently been recognized as a potential biofuel
      feedstock crop. Significant phenotypic variation including ploidy is present
      across the two primary ecotypes of switchgrass, referred to as upland and lowland
      switchgrass. The tetraploid switchgrass genome is approximately 1400 Mbp, split
      between two subgenomes, with significant repetitive sequence content limiting the
      efficiency of re-sequencing approaches for determining genome diversity. To
      characterize genetic diversity in upland and lowland switchgrass as a first step
      in linking genotype to phenotype, we designed an exome capture probe set based on
      transcript assemblies that represent approximately 50 Mb of annotated switchgrass
      exome sequences. We then evaluated and optimized the probe set using solid phase
      comparative genome hybridization and liquid phase exome capture followed by next
      generation sequencing. Using the optimized probe set, we assessed variation in
      the exomes of eight switchgrass genotypes representing tetraploid lowland and
      octoploid upland cultivars to benchmark our exome capture probe set design. We
      identified ample variation in the switchgrass genome including 1,395,501 single
      nucleotide polymorphisms (SNPs), 8173 putative copy number variants and 3336
      presence/absence variants. While the majority of the SNPs (84%) detected was bi
      allelic, a substantial number was tri-allelic with limited occurrence of tetra
      allelic polymorphisms consistent with the heterozygous and polyploid nature of
      the switchgrass genome. Collectively, these data demonstrate the efficacy of
      exome capture for discovery of genome variation in a polyploid species with a
      large, repetitive and heterozygous genome.

PMID- 24947487
TI  - Demonstration of a lexical access deficit in relapsing-remitting and secondary
      progressive forms of multiple sclerosis.
AB  - The commonly used test to evaluate naming ability in multiple sclerosis (MS) is
      the Boston Naming Test (BNT). In previous studies the BNP has not shown any
      specific deficit in MS patients. The BNT score is obtained by adding
      spontaneously correct answers to correct answers obtained after semantic and
      phonological clues are given. Our hypothesis was that due to a lexical access
      deficit based on executive dysfunction, MS patients would need more clues than
      control subjects to normalize their performances,. Fifteen relapsing-remitting
      (RR) and 17 secondary progressive (SP) MS patients, and 32 controls matched for
      sex, age, and educational level, took the BNT. The 32 MS patients also took the
      BCCog (Short French battery used in MS to evaluate cognitive functions) in order
      to evaluate their executive functions. MS patients needed significantly more
      clues than matched controls to normalize their performances (P<0.001). This
      lexical access deficit was more frequent in the SP than in the RR group (P<0.05).
      A lexical access deficit inducing a denomination problem has thus been shown in
      MS patients. Further research should aim to better evaluate the executive
      functions of patients with a lexical access deficit. 

PMID- 24947489
TI  - Determination of pyrazole and pyrrole pesticides in environmental water samples
      by solid-phase extraction using multi-walled carbon nanotubes as adsorbent
      coupled with high-performance liquid chromatography.
AB  - A solid-phase extraction (SPE) method using multi-walled carbon nanotubes as
      adsorbent coupled with high-performance liquid chromatography was developed for
      the determination of four pyrazole and pyrrole pesticides (fenpyroximate,
      chlorfenapyr, fipronil and flusilazole) in environmental water samples. Several
      parameters, such as extraction adsorbent, elution solvent and volume and sample
      loading flow rate were optimized to obtain high SPE recoveries and extraction
      efficiency. The calibration curves for the pesticides extracted were linear in
      the range of 0.05-10 MUg L(-1) for chlorfenapyr and fenpyroximate and 0.05-20 MUg
      L(-1) for fipronil and flusilazole, with the correlation coefficients (r(2))
      between 0.9966 and 0.9990. The method gave good precisions (relative standard
      deviation %) from 2.9 to 10.1% for real spiked samples from reservoir water and
      seawater; method recoveries ranged 92.2-105.9 and 98.5-103.9% for real spiked
      samples from reservoir water and seawater, respectively. Limits of detection (S/N
      = 3) for the method were determined to be 8-19 ng L(-1). The optimized method was
      successfully applied to the determination of four pesticides of pyrazoles and
      pyrroles in real environmental water samples. 

PMID- 24947490
TI  - Strong anisotropy of Dirac cones in SrMnBi2 and CaMnBi2 revealed by angle
      resolved photoemission spectroscopy.
AB  - The Dirac materials, such as graphene and three-dimensional topological
      insulators, have attracted much attention because they exhibit novel quantum
      phenomena with their low energy electrons governed by the relativistic Dirac
      equations. One particular interest is to generate Dirac cone anisotropy so that
      the electrons can propagate differently from one direction to the other, creating
      an additional tunability for new properties and applications. While various
      theoretical approaches have been proposed to make the isotropic Dirac cones of
      graphene into anisotropic ones, it has not yet been met with success. There are
      also some theoretical predictions and/or experimental indications of anisotropic
      Dirac cone in novel topological insulators and AMnBi2 (A = Sr and Ca) but more
      experimental investigations are needed. Here we report systematic high resolution
      angle-resolved photoemission measurements that have provided direct evidence on
      the existence of strongly anisotropic Dirac cones in SrMnBi2 and CaMnBi2.
      Distinct behaviors of the Dirac cones between SrMnBi2 and CaMnBi2 are also
      observed. These results have provided important information on the strong
      anisotropy of the Dirac cones in AMnBi2 system that can be governed by the spin
      orbital coupling and the local environment surrounding the Bi square net. 

PMID- 24947491
TI  - A computational study of whole-brain connectivity in resting state and task fMRI.
AB  - BACKGROUND: We compared the functional brain connectivity produced during resting
      state in which subjects were not actively engaged in a task with that produced
      while they actively performed a visual motion task (task-state). MATERIAL AND
      METHODS: In this paper we employed graph-theoretical measures and network
      statistics in novel ways to compare, in the same group of human subjects,
      functional brain connectivity during resting-state fMRI with brain connectivity
      during performance of a high level visual task. We performed a whole-brain
      connectivity analysis to compare network statistics in resting and task states
      among anatomically defined Brodmann areas to investigate how brain networks
      spanning the cortex changed when subjects were engaged in task performance.
      RESULTS: In the resting state, we found strong connectivity among the posterior
      cingulate cortex (PCC), precuneus, medial prefrontal cortex (MPFC), lateral
      parietal cortex, and hippocampal formation, consistent with previous reports of
      the default mode network (DMN). The connections among these areas were
      strengthened while subjects actively performed an event-related visual motion
      task, indicating a continued and strong engagement of the DMN during task
      processing. Regional measures such as degree (number of connections) and
      betweenness centrality (number of shortest paths), showed that task performance
      induces stronger inter-regional connections, leading to a denser processing
      network, but that this does not imply a more efficient system as shown by the
      integration measures such as path length and global efficiency, and from global
      measures such as small-worldness. CONCLUSIONS: In spite of the maintenance of
      connectivity and the "hub-like" behavior of areas, our results suggest that the
      network paths may be rerouted when performing the task condition.

PMID- 24947492
TI  - Esophageal carcinoma: Evaluation with q-space diffusion-weighted MR imaging ex
      vivo.
AB  - PURPOSE: To determine the usefulness of q-space MR imaging as means of evaluating
      the depth of mural invasion, the histologic grades, and lymph node metastasis in
      esophageal carcinomas. METHODS: Twenty esophageal specimens each containing a
      carcinoma were studied with a 7.0 Tesla MR imaging system. q-Space MR images were
      obtained with a 50-60 mm * 25-30 mm field of view, 256 * 128 matrix, 2 mm section
      thickness, 10 b values ranging from 0 to 7163 s/mm(2) , and a motion-probing
      gradient in the y-direction, and the MR images were compared with the
      histopathologic findings. RESULTS: The mean displacement maps, probability for
      zero displacement maps, and kurtosis maps in all 20 carcinomas (100%) made it
      possible to identify the depth of tumor invasion of the esophageal wall. These q
      space MR imaging parameters were significantly correlated with the histologic
      grades of the esophageal carcinomas (P < 0.01), and also significantly correlated
      with their nuclear-cytoplasmic ratios (P < 0.01 or P < 0.001) and tumor
      cellularity (cell density) (P < 0.01 or P < 0.001). The q-space MR imaging
      parameters were also capable of differentiating between the metastatic lymph
      nodes and nonmetastatic lymph nodes (P < 0.01). CONCLUSION: q-Space MR imaging ex
      vivo provides excellent diagnostic accuracy for evaluating mural invasion by
      esophageal carcinomas, the histologic grades of esophageal carcinomas, and lymph
      node metastasis by esophageal carcinomas.

PMID- 24947493
TI  - Effects of moderate hepatic impairment on the pharmacokinetic properties and
      tolerability of umeclidinium and vilanterol in inhalational umeclidinium
      monotherapy and umeclidinium/vilanterol combination therapy: an open-label,
      nonrandomized study.
AB  - BACKGROUND: The long-acting muscarinic antagonist umeclidinium (UMEC) is approved
      as a monotherapy, and in combination with the long-acting beta2-agonist
      vilanterol (VI), as a once-daily inhaled maintenance bronchodilator therapy for
      chronic obstructive pulmonary disease in the US and EU; they are not indicated
      for the treatment of asthma. Preclinical and clinical data suggest that UMEC and
      VI are predominantly eliminated by the liver. OBJECTIVES: The objectives of the
      study were to evaluate the effects of moderate hepatic impairment on the plasma
      and urinary pharmacokinetic properties of each drug, and on the tolerability of
      inhalational UMEC/VI 125/25 ug and UMEC 125 ug. METHODS: This open-label,
      nonrandomized study was conducted in patients with moderate hepatic impairment
      (Child-Pugh score, 7-9) and in healthy volunteers (control). Patients and
      volunteers were administered a single dose of UMEC/VI 125/25 ug, and, after a 7-
      to 14-day washout period, repeat-dose UMEC 125 ug once daily for 7 days. Primary
      end points were the plasma pharmacokinetic properties of single- and repeat-dose
      UMEC and VI. Secondary end points were the urinary pharmacokinetic properties of
      UMEC, and the tolerability of each treatment. RESULTS: All 18 enrolled patients
      and volunteers (12 men, 6 women; mean age, 53.6 years) completed the study. Mean
      systemic exposures of UMEC and VI were similar or numerically lower in patients
      with moderate hepatic impairment compared with those in healthy volunteers, but
      the differences were not clinically significant. UMEC accumulations with 7-day
      dosing of UMEC were similar between patients with moderate hepatic impairment and
      healthy volunteers. UMEC/VI 125/25 ug and UMEC 125 ug were well-tolerated, with
      no safety concerns identified. CONCLUSIONS: The administration of UMEC/VI 125/25
      ug or UMEC 125 ug in patients with moderate hepatic impairment did not result in
      clinically relevant increases in UMEC or VI exposures compared with those in
      healthy volunteers. Based on these findings, no dose adjustment for UMEC/VI or
      UMEC is warranted in patients with moderate hepatic impairment.

PMID- 24947494
TI  - The cost of blood collection in Greece: an economic analysis.
AB  - OBJECTIVE: The goal of this study was to estimate the cost of production of 1
      unit of blood from a National Health Service perspective in Greece. METHODS: In
      agreement with guidelines, the cost of blood production in this study accounted
      only for the resources expended for collection, processing, laboratory testing,
      and storage. Hence, the costs associated with donor recruitment, pretransfusion
      preparation, transfusion administration, follow-up management of adverse events,
      and other long-term relevant costs were not taken into consideration. The
      indirect cost of blood donations for donors (productivity loss) was also
      considered. A questionnaire was used to collect data regarding personnel time,
      annual blood quantities collected, percentage of wastage, utilization of
      consumables, institutional overhead, information technology expenditure, medical
      equipment utilized, nuclear acid tests, and other factors. Data gathered by 53
      hospitals across the country were assessed. A model was constructed with economic
      data collected by the National School of Public Health and the Ministry of
      Health. All data refer to the year 2013. RESULTS: The weighted mean direct cost
      of producing 1 unit of blood was estimated at ?131.49 (SD, ?22.12;
      minimum/maximum, ?94.96-?239.20). The mean total indirect cost was estimated at
      ?34 per unit of blood. The cost distribution was positively skewed (skewness,
      1.642 [0.327]). The major cost component was the cost of personnel, accounting
      for 32.5% of total costs, and the average of blood unit wastage was estimated at
      4.90%. There were no differences between the cost of producing 1 unit of blood in
      Athens compared with the rest of the country (Mann-Whitney test, P = 0.341).
      CONCLUSIONS: This study suggests that the cost of producing 1 unit of blood is
      not insignificant. These figures need to be complemented with those concerning
      the cost of transfusion to have a complete picture of producing and using 1 unit
      of blood locally.

PMID- 24947495
TI  - Upfront autologous stem-cell transplantation with melphalan, cyclophosphamide,
      etoposide, and dexamethasone (LEED) in patients with newly diagnosed primary
      central nervous system lymphoma.
AB  - Treatment of primary central nervous system lymphoma (PCNSL) improved in recent
      years. However, the high neurotoxicity and low survival rates associated with
      this condition remain unresolved. We report 13 consecutive patients with PCNSL
      for whom upfront melphalan, cyclophosphamide, etoposide, and dexamethasone (known
      as LEED) followed by autologous stem-cell transplantation (ASCT) was planned at
      the Anjo Kosei Hospital. All patients were pathologically diagnosed with diffuse
      large B-cell lymphoma and were negative for human immunodeficiency virus. All
      patients were to receive three cycles of high-dose methotrexate-based induction
      chemotherapy, two cycles of high-dose AraC-based chemotherapy, and LEED followed
      by ASCT. All 13 patients achieved a partial response, and the 3-year overall
      survival (OS) rate was 76.2 %. Seven of the 13 patients were alive at the last
      follow-up, without any adverse events, including neurotoxicity. Six of the 13
      (46.2 %) patients underwent ASCT and the 3-year OS rate was 80.0 %. Although this
      study included only a limited number of patients, these preliminary signs of
      efficacy and tolerability merit further consideration. To make further
      improvements in survival, the rate of patients undergoing ASCT should be
      increased. Other prospective studies involving greater numbers of patients are
      required to confirm these findings.

PMID- 24947496
TI  - Impact of metal pollution on fungal diversity and community structures.
AB  - The impact of metal pollution on plant communities has been studied extensively
      in the past, but little is known about the effects of metal pollution on fungal
      communities that occur in metal-polluted soils. Metal-tolerant ecotypes of the
      ectomycorrhizal fungus Suillus luteus are frequently found in pioneer pine
      forests in the Campine region in Belgium on metal-polluted soils. We hypothesized
      that metal pollution would play an important role in shaping below-ground fungal
      communities that occur in these soils and that Suillus luteus would be a dominant
      player. To test these hypotheses, the fungal communities in a young pine
      plantation in soil polluted with zinc, and cadmium were studied using 454
      amplicon pyrosequencing. Results show that zinc, cadmium and soil organic matter
      content were strongly correlated with the fungal community composition, but no
      effects on fungal diversity were observed. As hypothesized, S. luteus was found
      to be a dominant member of the studied fungal communities. However, other
      dominant fungal species, such as Sistotrema sp., Wilcoxina mikolae and Cadophora
      finlandica were found as well. Their presence in metal-polluted sites is
      discussed.

PMID- 24947497
TI  - Does preoperative subscapularis fatty muscle infiltration really matter in
      anterosuperior rotator cuff tears repair outcomes? A prospective multicentric
      study.
AB  - INTRODUCTION: Anterosuperior (AS) rotator cuff tear describes a combined tear of
      the subscapularis and the supraspinatus tendons. We hypothesized that results
      after AS tendon repairs might be influenced by the size of the subscapularis
      rupture and the preoperative subscapularis muscle fatty infiltration. METHODS: A
      prospective multicentric study of 53 AS rotator cuff tears from five centers was
      performed (January 2008-January 2009). Subscapularis tendon retraction and fatty
      infiltration were assessed preoperatively. An ultrasonographic healing control
      was performed 1 year after surgery. RESULTS: Patients were on average 60 years
      (range, 43-75 years) and were operated on average 16 months (range, 2-72 months)
      after the beginning of their symptoms. The incidence of AS tears was found to be
      18%. Average follow-up was 15 months (range, 12-24). The Constant-Murley (CM)
      score for the patients with AS ruptures improved significantly from 49 points
      (range, 35-51 points) preoperatively to 73 points postoperatively (range, 50-95
      points)(P=0.0205). CM score gains were 26 for Lafosse group 1 ruptures and 29 for
      Lafosse group 2 & 3 with pre- and postoperative P values at P<0.0000001 and
      P<0.000001, respectively. The last follow-up CM score according to the
      subscapularis fatty infiltration was 70 (range, 48-95) for groups 0-1, 70 (range,
      56-87) for group 2, and 56 (range, 53-88) for groups 3-4 with pre- and
      postoperative P values at P<0.001, P<0.001, and P<0.004, respectively. The global
      retear rate was 6%. DISCUSSION: Our study showed that the CM score after repairs
      of AS rotator cuff tears was lower in advanced subscapularis fatty infiltration.
      However, gains in CM scores were similar whatever the initial subscapularis fatty
      infiltration. The rate of tendon healing was correlated with subscapularis fatty
      infiltration. Subscapularis tendon rupture size was not significantly correlated
      with outcomes. LEVEL OF EVIDENCE: Level III.

PMID- 24947498
TI  - A pre-ribosomal RNA interaction network involving snoRNAs and the Rok1 helicase.
AB  - Ribosome biogenesis in yeast requires 75 small nucleolar RNAs (snoRNAs) and a
      myriad of cofactors for processing, modification, and folding of the ribosomal
      RNAs (rRNAs). For the 19 RNA helicases implicated in ribosome synthesis, their
      sites of action and molecular functions have largely remained unknown. Here, we
      have used UV cross-linking and analysis of cDNA (CRAC) to reveal the pre-rRNA
      binding sites of the RNA helicase Rok1, which is involved in early small subunit
      biogenesis. Several contact sites were identified in the 18S rRNA sequence, which
      interestingly all cluster in the "foot" region of the small ribosomal subunit.
      These include a major binding site in the eukaryotic expansion segment ES6, where
      Rok1 is required for release of the snR30 snoRNA. Rok1 directly contacts snR30
      and other snoRNAs required for pre-rRNA processing. Using cross-linking, ligation
      and sequencing of hybrids (CLASH) we identified several novel pre-rRNA base
      pairing sites for the snoRNAs snR30, snR10, U3, and U14, which cluster in the
      expansion segments of the 18S rRNA. Our data suggest that these snoRNAs bridge
      interactions between the expansion segments, thereby forming an extensive
      interaction network that likely promotes pre-rRNA maturation and folding in early
      pre-ribosomal complexes and establishes long-range rRNA interactions during
      ribosome synthesis. 

PMID- 24947500
TI  - Induced ferromagnetism at BiFeO3/YBa2Cu3O7 interfaces.
AB  - Transition metal oxides (TMOs) exhibit many emergent phenomena ranging from high
      temperature superconductivity and giant magnetoresistance to magnetism and
      ferroelectricity. In addition, when TMOs are interfaced with each other, new
      functionalities can arise, which are absent in individual components. Here, we
      report results from first-principles calculations on the magnetism at the
      BiFeO3/YBa2Cu3O7 interfaces. By comparing the total energy for various magnetic
      spin configurations inside BiFeO3, we are able to show that a metallic
      ferromagnetism is induced near the interface. We further develop an interface
      exchange-coupling model and place the extracted exchange coupling interaction
      strengths, from the first-principles calculations, into a resultant generic phase
      diagram. Our conclusion of interfacial ferromagnetism is confirmed by the
      presence of a hysteresis loop in field-dependent magnetization data. The
      emergence of interfacial ferromagnetism should have implications to electronic
      and transport properties. 

PMID- 24947499
TI  - Nonsense-mediated decay factors are involved in the regulation of selenoprotein
      mRNA levels during selenium deficiency.
AB  - Selenoproteins contain the unique amino acid selenocysteine (Sec), which is
      encoded by the triplet UGA. Since UGA also serves as a stop codon, it has been
      postulated that selenoprotein mRNAs are targeted for degradation by the nonsense
      mediated mRNA decay pathway (NMD). Several reports have observed a hierarchy of
      selenoprotein mRNA expression when selenium (Se) is limiting, whereby the
      abundance of certain transcripts decline while others do not. We sought to
      investigate the role of NMD in this hierarchical response that selenoprotein
      mRNAs exhibit to environmental Se status. Selenoprotein mRNAs were categorized as
      being predicted sensitive or resistant to NMD based on the requirements held by
      the current model. About half of the selenoprotein transcriptome was predicted to
      be sensitive to NMD and showed significant changes in mRNA abundance in response
      to cellular Se status. The other half that was predicted to be resistant to NMD
      did not respond to Se status. RNA immunoprecipitation with essential NMD factor
      UPF1 revealed that the mRNAs that were the most sensitive to Se status were also
      the most enriched on UPF1 during Se deficiency. Furthermore, depletion of SMG1,
      the kinase responsible for UPF1 phosphorylation and NMD activation, abrogated the
      decline in transcript abundance of Se-responsive transcripts. Lastly, mRNA decay
      rates of Se-responsive transcripts were altered upon the addition of Se to
      resemble the slower decay rates of nonresponsive transcripts. Taken together,
      these results present novel evidence in support of a crucial role for the NMD
      pathway in regulating selenoprotein mRNA levels when Se is limiting. 

PMID- 24947501
TI  - Immediate effects of rapid maxillary expansion on the naso-maxillary facial soft
      tissue using 3D stereophotogrammetry.
AB  - BACKGROUND: Rapid maxillary expansion (RME) is used to expand the narrow maxilla.
      Dental and skeletal affects have previously been reported but few studies have
      reported on the overlying soft tissue changes. This study reports on the
      immediate effects of RME on the naso-maxillary facial soft tissue using 3D
      stereophotogrammetry. METHODS: Fourteen patients requiring upper arch expansion
      using RME as part of their full comprehensive orthodontic plan were recruited.
      Cone beam CT scans and stereophotogrammetry images were taken for each patient;
      pre-RME activation (T0) and immediately post-RME expansion (T1). Based on twenty
      three landmarks, 13 linear and 3 angular measurements were made from each of the
      stereophotogrammetry images. A linear measurement at ANS was taken from each CBCT
      image. Using a Wilcoxon signed rank test, the pre-RME and post-RME measurements
      were compared. RESULTS: The mean separation of the anterior nasal spine was 3.8
      mm +/- 1.2 mm. The largest median increase was in nasal base width (1.6 mm),
      which was statistically significant (p = 0.001). Changes in the nasal dorsum
      height, nasal tip protrusion, philtrum width, and upper lip length were not
      statistically significant (p < 0.05). No significant differences were observed in
      the nostril linear measurements, expect for columella width (p = 0.009). Naso
      labial angle decreased but was not statistically significant (p = 0.276). The
      only statically significant angular change was an increase in the nasal tip
      displacement angle (p = 0.001). CONCLUSION: Rapid maxillary expansion produces
      subtle changes in the naso-maxillary soft tissue complex. There is an increase in
      nasal base width, retraction and flattening of the nasal tip. These changes are
      small, less than 2 mm and variable between patients.

PMID- 24947502
TI  - Patient characteristics and risk of subsequent contralateral hip fracture after
      surgical management of first fracture.
AB  - BACKGROUND: Sequential hip fractures are associated with increased morbidity and
      mortality. Understanding of risk factors is important for secondary prevention.
      Although hip fractures have a multifactorial aetiology related to falls, it is
      unknown whether fracture management approach influences the risk of sequential
      hip fractures. OBJECTIVES: Our objective is to explore whether subsequent
      contralateral hip fractures are more common following femoral head replacement or
      salvage procedures for the treatment of hip fractures. METHODS: Patients older
      than 50, admitted to a single regional trauma unit in Worcestershire between 2010
      and 2012 were identified from the national database. 700 patients matched our
      inclusion criteria and case notes were reviewed. The male to female ratio was
      1:3.3 and the mean age was 82.8 years (standard deviation: 8.9 years).
      Contralateral fractures were identified from admission X-rays. Risk factors were
      analysed based on patient demographics and data related to first hip fracture
      management. RESULTS: Seventy-one patients presented with contralateral fractures,
      of which 19 had their first fracture during the data collection period,
      estimating a period prevalence of 10.1%, and incidence of 2.9%. Contralateral
      fracture rates were not significantly different between femoral head salvage and
      replacement procedures (P-value 0.683). Older institutionalised females with
      poorer mobility status were at greatest risk of contralateral hip fractures. Half
      (50.7%) of these occurred within 2 years of their first fracture. CONCLUSION: No
      additional risk was seen in either fixation approaches. Risk factors identified
      were in keeping with existing literature, which can help to identify high-risk
      groups for targeted prevention strategies.

PMID- 24947504
TI  - Impact of dose on the bioavailability of coffee chlorogenic acids in humans.
AB  - Single servings of coffee beverage containing low (412 MUmol), medium (635 MUmol)
      and high (795 MUmol) amounts of chlorogenic acids were administered to eleven
      healthy volunteers in a double-blind randomised controlled trial. Analysis of
      plasma and urine collected for 24 h revealed the presence of 12 metabolites in
      plasma and 16 metabolites in urine, principally in the form of sulphates, and to
      a lesser extent glucuronides of caffeic, ferulic, dihydrocaffeic and
      dihydroferulic acids, as well as intact feruloylquinic and caffeoylquinic acids,
      and sulphated caffeoylquinic acid lactones. Median values of peak plasma
      concentrations after increasing doses of chlorogenic acids were 1088, 1526 and
      1352 nM. In urine the median amounts of metabolites excreted after 24 h following
      consumption of the three coffees were 101, 160 and 125 MUmol, accounting for 24%,
      25% and 16% of the doses ingested. Peak plasma concentration and urinary
      excretion values showed trends towards a reduced bioavailability of chlorogenic
      acids associated with the highest dose ingested, when expressed as percentages of
      intake. Potential biomarkers of coffee intake were identified as feruloylquinic
      acids and sulphated caffeoylquinic acid lactones in plasma and urine with
      positive moderate to strong coefficients of determination for peak plasma
      concentrations (0.60-0.81) and amounts excreted in urine (0.36-0.73) (P < 0.05). 

PMID- 24947505
TI  - Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method
      to increase circulating progenitor cell concentration?
AB  - BACKGROUND: Our goal was to test whether short-term intermittent hypobaric
      hypoxia (IHH) at a level well tolerated by healthy humans could, in combination
      with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC)
      and increase their concentration in peripheral circulation. METHODS: Nine healthy
      male subjects were subjected, as the active group (HME), to a protocol involving
      IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric
      pressure of 540 hPa (equivalent to an altitude of 5000 m). These sessions took
      place on four consecutive days. ME was applied in two separate 20-minute periods
      during each IHH session. Blood samples were obtained from an antecubital vein on
      three consecutive days immediately before the experiment, and then 24 h, 48 h, 4
      days, 7 days and 14 days after the last day of hypoxic exposure. Four months
      later a control study was carried out involving seven of the original subjects
      (CG), who underwent the same protocol of blood samples but without receiving any
      special stimulus. RESULTS: In comparison with the CG the HME group showed only a
      non-significant increase in the number of CPC CD34+ cells on the fourth day after
      the combined IHH and ME treatment. CONCLUSION: CPC levels oscillated across the
      study period and provide no firm evidence to support an increased CPC count after
      IHH plus ME, although it is not possible to know if this slight increase observed
      is physiologically relevant. Further studies are required to understand CPC
      dynamics and the physiology and physiopathology of the hypoxic stimulus.

PMID- 24947506
TI  - Detection and characterization of phosphatidylcholine in various strains of the
      genus Chlamydomonas (Volvocales, Chlorophyceae).
AB  - The laboratory strains of Chlamydomonas reinhardtii have been reported to contain
      no phosphatidylcholine (PC), which is considered to be replaced by another
      zwitterionic lipid, diacylglyceryl-N,N,N-trimethylhomoserine (DGTS). According to
      the recently published classification, the strains belonged to the subgroup
      Reinhardtinia. Screening for PC in 13 selected strains of Chlamydomonas in the
      NIES Algal Collection, which are different in habitats and belong to different
      phylogenetic subgroups in the genus, revealed the presence of PC in four strains:
      a strain in the subgroup Polytominia, and three strains in Reinhardtinia. PC was
      not detected in three other strains of Reinhardtinia analyzed. The
      presence/absence of PC was not related to the phylogenetic relationship based on
      18S rRNA. DGTS was detected in all the strains analyzed. The rare isomer of
      linolenic acid, 18:3(5,9,12), which has been found in the DGTS of C. reinhardtii,
      was found in the PC of the two strains and in the DGTS of the five strains. The
      occurrence of this fatty acid seems limited to a branch of Reinhardtinia.
      Acquisition and loss of PC in various strains of Chlamydomonas are discussed from
      the viewpoint of evolution of PC biosynthetic pathway. 

PMID- 24947503
TI  - Rapid tests for the diagnosis of visceral leishmaniasis in patients with
      suspected disease.
AB  - BACKGROUND: The diagnosis of visceral leishmaniasis (VL) in patients with fever
      and a large spleen relies on showing Leishmania parasites in tissue samples and
      on serological tests. Parasitological techniques are invasive, require
      sophisticated laboratories, consume time, or lack accuracy. Recently, rapid
      diagnostic tests that are easy to perform have become available. OBJECTIVES: To
      determine the diagnostic accuracy of rapid tests for diagnosing VL in patients
      with suspected disease presenting at health services in endemic areas. SEARCH
      METHODS: We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded,
      Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without
      applying language or date limits. SELECTION CRITERIA: This review includes
      original, phase III, diagnostic accuracy studies of rapid tests in patients
      clinically suspected to have VL. As reference standards, we accepted: (1) direct
      smear or culture of spleen aspirate; (2) composite reference standard based on
      one or more of the following: parasitology, serology, or response to treatment;
      and (3) latent class analysis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed quality of included studies using the
      QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a
      meta-analysis to estimate sensitivity and specificity of rapid tests, using a
      bivariate normal model with a complementary log-log link function. We analysed
      each index test separately. As possible sources of heterogeneity, we explored:
      geographical area, commercial brand of index test, type of reference standard,
      disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a
      sensitivity analysis to assess the influence of imperfect reference standards.
      MAIN RESULTS: Twenty-four studies containing information about five index tests
      (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine,
      FAST agglutination test, rK26 ICT, and rKE16 ICT) recruiting 4271 participants
      (2605 with VL) were included. We carried out a meta-analysis for the rK39 ICT
      (including 18 studies; 3622 participants) and the latex agglutination test (six
      studies; 1374 participants). The results showed considerable heterogeneity. For
      the rK39 ICT, the overall sensitivity was 91.9% (95% confidence interval (95% CI)
      84.8 to 96.5) and the specificity 92.4% (95% CI 85.6 to 96.8). The sensitivity
      was lower in East Africa (85.3%; 95% CI 74.5 to 93.2) than in the Indian
      subcontinent (97.0%; 95% CI 90.0 to 99.5). For the latex agglutination test,
      overall sensitivity was 63.6% (95% CI 40.9 to 85.6) and specificity 92.9% (95% CI
      76.7 to 99.2). AUTHORS' CONCLUSIONS: The rK39 ICT shows high sensitivity and
      specificity for the diagnosis of visceral leishmaniasis in patients with febrile
      splenomegaly and no previous history of the disease, but the sensitivity is
      notably lower in east Africa than in the Indian subcontinent. Other rapid tests
      lack accuracy, validation, or both.

PMID- 24947507
TI  - Evidence supporting the 19 beta-strand model for Tom40 from cysteine scanning and
      protease site accessibility studies.
AB  - Most proteins found in mitochondria are translated in the cytosol and enter the
      organelle via the TOM complex (translocase of the outer mitochondrial membrane).
      Tom40 is the pore forming component of the complex. Although the three
      dimensional structure of Tom40 has not been determined, the structure of porin, a
      related protein, has been shown to be a beta-barrel containing 19 membrane
      spanning beta-strands and an N-terminal alpha-helical region. The evolutionary
      relationship between the two proteins has allowed modeling of Tom40 into a
      similar structure by several laboratories. However, it has been suggested that
      the 19-strand porin structure does not represent the native form of the protein.
      If true, modeling of Tom40 based on the porin structure would also be invalid. We
      have used substituted cysteine accessibility mapping to identify several
      potential beta-strands in the Tom40 protein in isolated mitochondria. These data,
      together with protease accessibility studies, support the 19 beta-strand model
      for Tom40 with the C-terminal end of the protein localized to the intermembrane
      space. 

PMID- 24947508
TI  - Sec23 homolog Nel1 is a novel GTPase-activating protein for Sar1 but does not
      function as a subunit of the coat protein complex II (COPII) coat.
AB  - The coat protein complex II (COPII) generates transport carriers from the
      endoplasmic reticulum (ER) under the control of the small GTPase Sar1. Sec23 is
      well known as a structural component of the COPII coat and as a GTPase-activating
      protein (GAP) for Sar1. Here, we showed that Saccharomyces cerevisiae contains a
      novel Sec23 paralog, Nel1, which appears not to function as a subunit of the
      COPII coat. Nel1 does not associate with any of the COPII components, but it
      exhibits strong Sar1 GAP activity. We also demonstrated that the chromosomal
      deletion of NEL1 leads to a significant growth defect in the temperature
      sensitive sar1D32G background, suggesting a possible functional link between
      these proteins. In contrast to Sec23, which is predominantly localized at ER exit
      sites on the ER membrane, a major proportion of Nel1 is localized throughout the
      cytosol. Our findings highlight a possible role of Nel1 as a novel GAP for Sar1. 

PMID- 24947509
TI  - Novel Kv7.1-phosphatidylinositol 4,5-bisphosphate interaction sites uncovered by
      charge neutralization scanning.
AB  - Kv7.1 to Kv7.5 alpha-subunits belong to the family of voltage-gated potassium
      channels (Kv). Assembled with the beta-subunit KCNE1, Kv7.1 conducts the slowly
      activating potassium current IKs, which is one of the major currents underlying
      repolarization of the cardiac action potential. A known regulator of Kv7 channels
      is the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 increases the
      macroscopic current amplitude by stabilizing the open conformation of 7.1/KCNE1
      channels. However, knowledge about the exact nature of the interaction is
      incomplete. The aim of this study was the identification of the amino acids
      responsible for the interaction between Kv7.1 and PIP2. We generated 13 charge
      neutralizing point mutations at the intracellular membrane border and
      characterized them electrophysiologically in complex with KCNE1 under the
      influence of diC8-PIP2. Electrophysiological analysis of corresponding long QT
      syndrome mutants suggested impaired PIP2 regulation as the cause for channel
      dysfunction. To clarify the underlying structural mechanism of PIP2 binding,
      molecular dynamics simulations of Kv7.1/KCNE1 complexes containing two PIP2
      molecules in each subunit at specific sites were performed. Here, we identified a
      subset of nine residues participating in the interaction of PIP2 and Kv7.1/KCNE1.
      These residues may form at least two binding pockets per subunit, leading to the
      stabilization of channel conformations upon PIP2 binding. 

PMID- 24947510
TI  - Exploring the structure of the voltage-gated Na+ channel by an engineered drug
      access pathway to the receptor site for local anesthetics.
AB  - Despite the availability of several crystal structures of bacterial voltage-gated
      Na(+) channels, the structure of eukaryotic Na(+) channels is still undefined. We
      used predictions from available homology models and crystal structures to
      modulate an external access pathway for the membrane-impermeant local anesthetic
      derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel.
      Potassium channel-based homology models predict amino acid Ile-1575 in domain IV
      segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop
      selectivity filter. The mutation K1237E has been shown previously to increase the
      diameter of the selectivity filter. We found that an access pathway for external
      QX-222 created by mutations of Ile-1575 was abolished by the additional mutation
      K1237E, supporting the notion of a close spatial relationship between sites 1237
      and 1575. Crystal structures of bacterial voltage-gated Na(+) channels predict
      that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into
      the space between domain IV segment 6 and domain III pore-loop and, therefore,
      should obstruct the putative external access pathway. Indeed, mutations W1531A
      and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G
      created a second non-selective ion-conducting pore, bypassing the outer vestibule
      but probably merging into the internal vestibule, allowing for control by the
      activation gate. These data suggest a strong structural similarity between
      bacterial and eukaryotic voltage-gated Na(+) channels. 

PMID- 24947511
TI  - Actin enables the antimicrobial action of LL-37 peptide in the presence of
      microbial proteases.
AB  - Host defense peptides play an important host-protective role by their microcidal
      action, immunomodulatory functions, and tissue repair activities. Proteolysis is
      a common strategy of pathogens used to neutralize host defense peptides. Here, we
      show that actin, the most abundant structural protein in eukaryotes, binds the LL
      37 host defense peptide, protects it from degradation by the proteases of
      Pseudomonas aeruginosa and Porphyromonas gingivalis, and enables its
      antimicrobial activity despite the presence of the proteases. Co-localization of
      LL-37 with extracellular actin was observed in necrotized regions of samples from
      oral lesions. Competition assays, cross-linking experiments, limited proteolysis,
      and mass spectrometry revealed that LL-37 binds by specific hydrophobic
      interactions to the His-40-Lys-50 segment of actin, located in the DNase I
      binding loop. The integrity of the binding site of both LL-37 and actin is a
      prerequisite to the binding. Our results demonstrate that actin, presumably
      released by dead cells and abundant in infected sites, might be utilized by the
      immune system to enhance spatio-temporal immunity in an attempt to arrest
      infection and control inflammation. 

PMID- 24947512
TI  - Thymine DNA glycosylase is a CRL4Cdt2 substrate.
AB  - The E3 ubiquitin ligase CRL4(Cdt2) targets proteins for destruction in S phase
      and after DNA damage by coupling ubiquitylation to DNA-bound proliferating cell
      nuclear antigen (PCNA). Coupling to PCNA involves a PCNA-interacting peptide
      (PIP) degron motif in the substrate that recruits CRL4(Cdt2) while binding to
      PCNA. In vertebrates, CRL4(Cdt2) promotes degradation of proteins whose presence
      in S phase is deleterious, including Cdt1, Set8, and p21. Here, we show that
      CRL4(Cdt2) targets thymine DNA glycosylase (TDG), a base excision repair enzyme
      that is involved in DNA demethylation. TDG contains a conserved and nearly
      perfect match to the PIP degron consensus. TDG is ubiquitylated and destroyed in
      a PCNA-, Cdt2-, and PIP degron-dependent manner during DNA repair in Xenopus egg
      extract. The protein can also be destroyed during DNA replication in this system.
      During Xenopus development, TDG first accumulates during gastrulation, and its
      expression is down-regulated by CRL4(Cdt2). Our results expand the group of
      vertebrate CRL4(Cdt2) substrates to include a bona fide DNA repair enzyme. 

PMID- 24947513
TI  - Mutagenesis studies of the H5 influenza hemagglutinin stem loop region.
AB  - Influenza outbreaks, particularly the pandemic 1918 H1 and avian H5 strains, are
      of high concern to public health. The hemagglutinin envelope protein of influenza
      plays a critical role in viral entry and thus is an attractive target for
      inhibition of virus entry. The highly conserved stem loop region of hemagglutinin
      has been shown to undergo critically important conformational changes during the
      entry process and, moreover, to be a site for inhibition of virus entry by
      antibodies, small proteins, and small drug-like molecules. In this work we probe
      the structure-function properties of the H5 hemagglutinin stem loop region by
      site-directed mutagenesis. We find that most mutations do not disrupt expression,
      proteolytic processing, incorporation into virus, or receptor binding; however,
      many of the mutations disrupt the entry process. We further assess the effects of
      mutations on inhibition of entry by a neutralizing monoclonal antibody (C179) and
      find examples of increased and decreased sensitivity to the antibody, consistent
      with the antibody binding site observed by x-ray crystallography. In addition, we
      tested the sensitivity of the mutants to MBX2329, a small molecule inhibitor of
      influenza entry. Interestingly, the mutants exhibit increased and decreased
      sensitivities to MBX2329, which gives further insight into the binding site of
      the compound on HA and potential mechanisms of escape. Finally, we have modeled
      the binding site of MBX2329 using molecular dynamics and find that the resulting
      structure is in good agreement with the mutagenesis results. Together these
      studies underscore the importance of the stem loop region to HA function and
      suggest potential sites for therapeutic intervention of influenza entry. 

PMID- 24947514
TI  - Calcineurin-mediated YB-1 dephosphorylation regulates CCL5 expression during
      monocyte differentiation.
AB  - Y-box (YB) protein-1 serves as a master regulator in gene transcription and mRNA
      translation. YB-1 itself is regulated at various levels, e.g. through post
      translational modifications. In our previous work, we identified RANTES/CCL5 as a
      transcriptional target of YB-1. We previously demonstrated that YB-1 protein is
      transiently up-regulated during monocyte/macrophage differentiation evidenced in
      monocytic cells (THP-1 cells) that were differentiated using phorbol myristate
      acetate (PMA). Here we provide evidence that YB-1 phosphorylation, specifically
      at its serine residue 102 (Ser-102), increases early on in THP-1 cells following
      PMA treatment as well as in differentiated primary human monocytes. This process
      is mediated through the Akt signaling pathway. Ser-102-phosphorylated YB-1
      displays stronger binding affinity and trans-activating capacity at the CCL5 gene
      promoter. Notably, Ser-102-phosphorylated YB-1 disappears at later stages of the
      monocyte/macrophage differentiation process. We demonstrate that serine-threonine
      phosphatase calcineurin (CN) dephosphorylates YB-1 preventing it from binding to
      and trans-activating the CCL5 promoter. Co-immunoprecipitation assays prove a
      direct YB-1/CN interaction. Furthermore, analyses in kidney tissues from mice
      that were treated with the CN inhibitor cyclosporine A revealed an in vivo effect
      of CN on the YB-1 phosphorylation status. We conclude that YB-1 phosphorylation
      at Ser-102 is an important prerequisite for CCL5 promoter activation during
      macrophage differentiation. Our findings point to a critical role of YB-1 in the
      resolution of inflammatory processes which may largely be due to CN-mediated
      dephosphorylation. 

PMID- 24947515
TI  - The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B)
      transcription factor Relish in the Drosophila innate immune response.
AB  - The host defense of the model organism Drosophila is under the control of two
      major signaling cascades controlling transcription factors of the NF-B family,
      the Toll and the immune deficiency (IMD) pathways. The latter shares extensive
      similarities with the mammalian TNF-R pathway and was initially discovered for
      its role in anti-Gram-negative bacterial reactions. A previous interactome study
      from this laboratory reported that an unexpectedly large number of proteins are
      binding to the canonical components of the IMD pathway. Here, we focus on DNA
      methyltransferase-associated protein 1 (DMAP1), which this study identified as an
      interactant of Relish, a Drosophila transcription factor reminiscent of the
      mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in
      S2 cells and in flies results in a significant reduction of Escherichia coli
      induced expression of antimicrobial peptides. Epistatic analysis indicates that
      DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation
      experiments further reveal that, in addition to Relish, DMAP1 also interacts with
      Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these
      results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway,
      possibly acting at the level of chromatin remodeling.

PMID- 24947516
TI  - Multiple interactions of the intrinsically disordered region between the helicase
      and nuclease domains of the archaeal Hef protein.
AB  - Hef is an archaeal protein that probably functions mainly in stalled replication
      fork repair. The presence of an unstructured region was predicted between the two
      distinct domains of the Hef protein. We analyzed the interdomain region of
      Thermococcus kodakarensis Hef and demonstrated its disordered structure by CD,
      NMR, and high speed atomic force microscopy (AFM). To investigate the functions
      of this intrinsically disordered region (IDR), we screened for proteins
      interacting with the IDR of Hef by a yeast two-hybrid method, and 10 candidate
      proteins were obtained. We found that PCNA1 and a RecJ-like protein specifically
      bind to the IDR in vitro. These results suggested that the Hef protein interacts
      with several different proteins that work together in the pathways downstream
      from stalled replication fork repair by converting the IDR structure depending on
      the partner protein. 

PMID- 24947518
TI  - Children consuming milk cereal drink are at increased risk for overweight: The
      IDEFICS Sweden study, on behalf of the IDEFICS Consortium.
AB  - AIMS: The aims of this study were to characterize milk cereal drink (MCD)
      consumption among Swedish children and to investigate the association between MCD
      and overweight in a longitudinally followed cohort of children over 2 years of
      age. METHODS: In the Swedish cohort from IDEFICS (Identification and prevention
      of Dietary- and lifestyle-induced health EFfects In Children and infantS) we
      examined early feeding practices and weight status when children were aged 2-9
      years (2007/2008) and at 2-year follow-up. Weight and height were measured at
      both time points in 1077 children. Characteristics of MCD consumers were explored
      with logistic regression. Body mass index (BMI) z-scores at both time points and
      weight status at follow-up were regressed on explanatory factors using mixed
      linear and logistic regression, respectively. RESULTS: Nearly 69% of children had
      consumed MCD. The MCD consumers were more likely than never-consumers to have two
      native Swedish parents, parents with less than 2 years of post-secondary
      education, and a shorter period of breastfeeding. MCD consumers had a higher BMI
      z-score at follow-up compared with baseline (difference in BMI z-score=0.12, 95%
      confidence interval (CI)=0.07, 0.17), while the average BMI z-score in non
      consumers remained stable over time (0.00, 95% CI= -0.07, 0.07). MCD consumers
      were nearly five times more likely than non-consumers to become overweight during
      the follow-up (odds ratio (OR)=4.78, 95% CI=1.68, 13.59), independent of
      breastfeeding. CONCLUSIONS: MCD was consumed by the majority of children in this
      study. MCD consumption is associated with an increased risk for overweight and
      less exposure to breastfeeding. Our findings motivate future research aimed at
      investigating how MCD should be recommended.

PMID- 24947517
TI  - The putative exchange factor Gef3p interacts with Rho3p GTPase and the septin
      ring during cytokinesis in fission yeast.
AB  - The small GTP-binding proteins of the Rho family and its regulatory proteins play
      a central role in cytokinetic actomyosin ring assembly and cytokinesis. Here we
      show that the fission yeast guanine nucleotide exchange factor Gef3p interacts
      with Rho3p at the division site. Gef3p contains a putative DH homology domain and
      a BAR/IMD-like domain. The protein localized to the division site late in
      mitosis, where it formed a ring that did not constrict with actomyosin ring
      (cytokinetic actomyosin ring) invagination; instead, it split into a double ring
      that resembled the septin ring. Gef3p co-localized with septins and Mid2p and
      required septins and Mid2p for its localization. Gef3p interacts physically with
      the GTP-bound form of Rho3p. Although Gef3p is not essential for cell separation,
      the simultaneous disruption of gef3(+) and Rho3p-interacting proteins, such as
      Sec8p, an exocyst component, Apm1p, a subunit of the clathrin adaptor complex or
      For3p, an actin-polymerizing protein, yielded cells with strong defects in
      septation and polarity respectively. Our results suggest that interactions
      between septins and Rho-GEFs provide a new targeting mechanism for GTPases in
      cytokinesis, in this case probably contributing to Rho3p function in vesicle
      tethering and vesicle trafficking in the later steps of cell separation. 

PMID- 24947519
TI  - Ectonucleotide pyrophosphatase/phosphodiesterase activity in Neuro-2a
      neuroblastoma cells: changes in expression associated with neuronal
      differentiation.
AB  - Neuro-2a (N2a) neuroblastoma cells display an ectoenzymatic hydrolytic activity
      capable of degrading diadenosine polyphosphates. The Apn A-cleaving activity has
      been analysed with the use of the fluorogenic compound BODIPY FL guanosine 5'-O
      (3-thiotriphosphate) thioester. Hydrolysis of this dinucleotide analogue showed a
      hyperbolic kinetic with a Km value of 4.9 +/- 1.3 MUM. Diadenosine
      pentaphosphate, diadenosine tetraphosphate, diadenosine triphosphate, and the
      nucleoside monophosphate AMP behaved as an inhibitor of BODIPY FL guanosine 5'-O
      (3-thiotriphosphate) thioester extracellular degradation. Ectoenzymatic activity
      shared the typical characteristics of the ectonucleotide
      pyrophosphatase/phosphodiesterase family, as hydrolysis reached maximal activity
      at alkaline pH and was dependent on the presence of divalent cations, being
      strongly inhibited by EDTA and activated by Zn(2+) ions. Both NPP1 and NPP3
      isozymes are expressed in N2a cells, their expression levels substantially
      changing when cells differentiate into a neuronal-like phenotype. In this sense,
      it is relevant to point the expression pattern of the NPP3 protein, whose levels
      were drastically reduced in the differentiated cells, being almost completely
      absent after 24 h of differentiation. Enzymatic activity assays carried out with
      differentiated N2a cells showed that NPP1 is the main isozyme involved in the
      extracellular degradation of dinucleotides in these cells, this enzyme reducing
      its activity and changing its subcellular location following neuronal
      differentiation. We described the presence of an ectoenzymatic activity able to
      hydrolyse diadenosine polyphosphates (ApnA) in N2a cells. This activity displays
      biochemical features that are typical of the ectonucleotide
      pyrophosphatase/phosphodiesterase (E-NPP) family members, as demonstrated by the
      use of the fluorogenic compound BODIPY-FL-GTPgammaS. Both NPP1 and NPP3
      ectoenzymes are expressed in N2a cells, their levels dramatically changing when
      cells differentiate into a neuronal-like phenotype. Activity assays in
      differentiated cells showed that the ApnA-hydrolytic activity largely depends on
      the NPP1 isozyme.

PMID- 24947520
TI  - Yellow fever risk assessment in the Central African Republic.
AB  - BACKGROUND: Starting in 2008, the Central African Republic (CAR) experienced an
      unprecedented number of reported yellow fever (YF) cases. A risk assessment of YF
      virus (YFV) activity was conducted to estimate potential disease risk and vaccine
      needs. METHODS: A multistage cluster sampling design was used to sample humans,
      non-human primates, and mosquitoes in distinct ecologic zones. Humans and non
      human primates were tested for YFV-specific antibodies; mosquitoes were tested
      for YFV RNA. RESULTS: Overall, 13.3% (125/938) of humans were found to have
      naturally-acquired YFV antibodies. Antibody levels were higher in zones in the
      southern and south central regions of CAR. All sampled non-human primates (n=56)
      were known YFV reservoirs; one tested positive for YFV antibodies. Several known
      YF vectors were identified including Aedes africanus, Ae. aegypti, Ae.
      luteocephalus, and Ae. simpsoni. Several more urban locations were found to have
      elevated Breateau and Container indices for Ae. aegypti. CONCLUSIONS: A country
      wide assessment of YF risk found YFV to be endemic in CAR. The potential for
      future YF cases and outbreaks, however, varied by ecologic zone. Improved
      vaccination coverage through mass campaign and childhood immunization was
      recommended to mitigate the YF risk.

PMID- 24947523
TI  - Mechanoresponsive networks controlling vascular inflammation.
AB  - Atherosclerosis is a chronic inflammatory disease of arteries that develops
      preferentially at branches and bends that are exposed to disturbed blood flow.
      Vascular function is modified by flow, in part, via the generation of mechanical
      forces that alter multiple physiological processes in endothelial cells. Shear
      stress has profound effects on vascular inflammation; high uniform shear stress
      prevents leukocyte recruitment to the vascular wall by reducing endothelial
      expression of adhesion molecules and other inflammatory proteins, whereas low
      oscillatory shear stress has the opposite effects. Here, we review the molecular
      mechanisms that underpin the effects of shear stress on endothelial inflammatory
      responses. They include shear stress regulation of inflammatory mitogen-activated
      protein kinase and nuclear factor-kappaB signaling. High shear suppresses these
      pathways through the induction of several negative regulators of inflammation,
      whereas low shear promotes inflammatory signaling. Furthermore, we summarize
      recent studies indicating that inflammatory signaling is highly sensitive to
      pulse wave frequencies, magnitude, and direction of flow. Finally, the importance
      of systems biology approaches (including omics studies and functional screening)
      to identify novel mechanosensitive pathways is discussed. 

PMID- 24947525
TI  - Factor XI regulates pathological thrombus formation on acutely ruptured
      atherosclerotic plaques.
AB  - OBJECTIVE: Coagulation factor XI is proposed as therapeutic target for
      anticoagulation. However, it is still unclear whether the antithrombotic
      properties of factor XI inhibitors influence atherosclerotic disease and
      atherothrombosis. Our aim is to investigate whether factor XI antisense
      oligonucleotides could prevent thrombus formation on acutely ruptured
      atherosclerotic plaques. APPROACH AND RESULTS: Atherosclerotic plaques in the
      carotid arteries of Apoe(-/-) mice were acutely ruptured using ultrasound. The
      subsequent thrombus formation was visualized and quantified by intravital
      microscopy and immunohistochemistry. Mice were pretreated with either factor XI
      antisense or nonsense oligonucleotides (50 mg/kg) to lower factor XI plasma
      levels. A tail bleeding assay was used to determine the safety. On plaque
      rupture, initial platelet adhesion and platelet plug formation were not impaired
      in animals treated with factor XI antisense oligonucleotides. However, the
      ensuing thrombus formation and fibrin deposition were significantly lower after 5
      to 10 minutes (P<0.05) in factor XI antisense oligonucleotide-treated animals
      without inducing a bleeding tendency. Furthermore, thrombi from antisense-treated
      animals were less stable than thrombi from placebo-treated animals. Moreover,
      macrophage infiltration and collagen deposition were lower in the carotid
      arteries of factor XI antisense-treated animals. No neutrophils were present.
      CONCLUSIONS: Factor XI antisense oligonucleotides safely prevent thrombus
      formation on acutely ruptured atherosclerotic plaques in mice. Furthermore,
      perturbed carotid arteries from factor XI antisense-treated animals show a less
      severe inflammatory response.

PMID- 24947524
TI  - NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to
      hypertensive vascular remodeling.
AB  - OBJECTIVE: Pulmonary hypertension (PH) is a progressive disease arising from
      remodeling and narrowing of pulmonary arteries (PAs) resulting in high pulmonary
      blood pressure and ultimately right ventricular failure. Elevated production of
      reactive oxygen species by NADPH oxidase 4 (Nox4) is associated with increased
      pressure in PH. However, the cellular location of Nox4 and its contribution to
      aberrant vascular remodeling in PH remains poorly understood. Therefore, we
      sought to identify the vascular cells expressing Nox4 in PAs and determine the
      functional relevance of Nox4 in PH. APPROACH AND RESULTS: Elevated expression of
      Nox4 was detected in hypertensive PAs from 3 rat PH models and human PH using
      qualititative real-time reverse transcription polymerase chain reaction, Western
      blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both
      endothelium and adventitia, and perivascular staining was prominently increased
      in hypertensive lung sections, colocalizing with cells expressing fibroblast and
      monocyte markers and matching the adventitial location of reactive oxygen species
      production. Small-molecule inhibitors of Nox4 reduced adventitial reactive oxygen
      species generation and vascular remodeling as well as ameliorating right
      ventricular hypertrophy and noninvasive indices of PA stiffness in monocrotaline
      treated rats as determined by morphometric analysis and high-resolution digital
      ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols
      and reduced the expression of fibroblast markers in isolated PAs. In fibroblasts,
      Nox4 overexpression stimulated migration and proliferation and was necessary for
      matrix gene expression. CONCLUSION: These findings indicate that Nox4 is
      prominently expressed in the adventitia and contributes to altered fibroblast
      behavior, hypertensive vascular remodeling, and development of PH.

PMID- 24947526
TI  - Endothelial deletion of phospholipase D2 reduces hypoxic response and
      pathological angiogenesis.
AB  - OBJECTIVE: Aberrant regulation of the proliferation, survival, and migration of
      endothelial cells (ECs) is closely related to the abnormal angiogenesis that
      occurs in hypoxia-induced pathological situations, such as cancer and vascular
      retinopathy. Hypoxic conditions and the subsequent upregulation of hypoxia
      inducible factor-1alpha and target genes are important for the angiogenic
      functions of ECs. Phospholipase D2 (PLD2) is a crucial signaling mediator that
      stimulates the production of the second messenger phosphatidic acid. PLD2 is
      involved in various cellular functions; however, its specific roles in ECs under
      hypoxia and in vivo angiogenesis remain unclear. In the present study, we
      investigated the potential roles of PLD2 in ECs under hypoxia and in hypoxia
      induced pathological angiogenesis in vivo. APPROACH AND RESULTS: Pld2 knockout
      ECs exhibited decreased hypoxia-induced cellular responses in survival,
      migration, and thus vessel sprouting. Analysis of hypoxia-induced gene expression
      revealed that PLD2 deficiency disrupted the upregulation of hypoxia-inducible
      factor-1alpha target genes, including VEGF, PFKFB3, HMOX-1, and NTRK2. Consistent
      with this, PLD2 contributed to hypoxia-induced hypoxia-inducible factor-1alpha
      expression at the translational level. The roles of PLD2 in hypoxia-induced in
      vivo pathological angiogenesis were assessed using oxygen-induced retinopathy and
      tumor implantation models in endothelial-specific Pld2 knockout mice. Pld2
      endothelial-specific knockout retinae showed decreased neovascular tuft
      formation, despite a larger avascular region. Tumor growth and tumor blood vessel
      formation were also reduced in Pld2 endothelial-specific knockout mice.
      CONCLUSIONS: Our findings demonstrate a novel role for endothelial PLD2 in the
      survival and migration of ECs under hypoxia via the expression of hypoxia
      inducible factor-1alpha and in pathological retinal angiogenesis and tumor
      angiogenesis in vivo.

PMID- 24947529
TI  - Computed tomography correlation of airway disease with bronchoscopy: part I-
      nonneoplastic large airway diseases.
AB  - To illustrate and describe computed tomographic large airway pathology and
      correlate with fiberoptic bronchoscopy findings. Commonly encountered diseases of
      the large airway include tracheobronchial amyloidosis, tracheobronchopathia
      osteochondroplastica, tracheobronchomegaly, laryngotracheobronchial
      papillomatosis, relapsing polychondritis, Wegener granulomatosis, sarcoidosis,
      and tracheal stenosis. Computed tomography manifestations and bronchoscopic
      findings of these selected large airway diseases are discussed. 

PMID- 24947527
TI  - Macrophage-independent regulation of reverse cholesterol transport by liver X
      receptors.
AB  - OBJECTIVE: The ability of high-density lipoprotein (HDL) particles to accept
      cholesterol from peripheral cells, such as lipid-laden macrophages, and to
      transport cholesterol to the liver for catabolism and excretion in a process
      termed reverse cholesterol transport (RCT) is thought to underlie the beneficial
      cardiovascular effects of elevated HDL. The liver X receptors (LXRs; LXRalpha and
      LXRbeta) regulate RCT by controlling the efflux of cholesterol from macrophages
      to HDL and the excretion, catabolism, and absorption of cholesterol in the liver
      and intestine. Importantly, treatment with LXR agonists increases RCT and
      decreases atherosclerosis in animal models. Nevertheless, LXRs are expressed in
      multiple tissues involved in RCT, and their tissue-specific contributions to RCT
      are still not well defined. APPROACH AND RESULTS: Using tissue-specific LXR
      deletions together with in vitro and in vivo assays of cholesterol efflux and
      fecal cholesterol excretion, we demonstrate that macrophage LXR activity is
      neither necessary nor sufficient for LXR agonist-stimulated RCT. In contrast, the
      ability of LXR agonists primarily acting in the intestine to increase HDL mass
      and HDL function seems to underlie the ability of LXR agonists to stimulate RCT
      in vivo. CONCLUSIONS: We demonstrate that activation of LXR in macrophages makes
      little or no contribution to LXR agonist-stimulated RCT. Unexpectedly, our
      studies suggest that the ability of macrophages to efflux cholesterol to HDL in
      vivo is not regulated by macrophage activity but is primarily determined by the
      quantity and functional activity of HDL.

PMID- 24947528
TI  - Transplanted perivascular adipose tissue accelerates injury-induced neointimal
      hyperplasia: role of monocyte chemoattractant protein-1.
AB  - OBJECTIVE: Perivascular adipose tissue (PVAT) expands during obesity, is highly
      inflamed, and correlates with coronary plaque burden and increased cardiovascular
      risk. We tested the hypothesis that PVAT contributes to the vascular response to
      wire injury and investigated the underlying mechanisms. APPROACH AND RESULTS: We
      transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the
      carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor
      knockout mice. Two weeks after transplantation, wire injury was performed, and
      animals were euthanized 2 weeks later. Immunohistochemistry was performed to
      quantify adventitial macrophage infiltration and neovascularization and
      neointimal lesion composition and size. Transplanted PVAT accelerated neointimal
      hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis.
      The majority of neointimal cells in PVAT-transplanted animals expressed alpha
      smooth muscle actin, consistent with smooth muscle phenotype. Deletion of
      monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects
      of fat transplantation on neointimal hyperplasia and adventitial angiogenesis,
      but not adventitial macrophage infiltration. Conditioned medium from perivascular
      adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses
      in cultured endothelial cells. CONCLUSIONS: These findings indicate that PVAT
      contributes to the vascular response to wire injury, in part through monocyte
      chemoattractant protein-1-dependent mechanisms.

PMID- 24947530
TI  - Practice guidelines for the diagnosis and management of skin and soft tissue
      infections: 2014 update by the infectious diseases society of America.
AB  - A panel of national experts was convened by the Infectious Diseases Society of
      America (IDSA) to update the 2005 guidelines for the treatment of skin and soft
      tissue infections (SSTIs). The panel's recommendations were developed to be
      concordant with the recently published IDSA guidelines for the treatment of
      methicillin-resistant Staphylococcus aureus infections. The focus of this
      guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging
      from minor superficial infections to life-threatening infections such as
      necrotizing fasciitis. In addition, because of an increasing number of
      immunocompromised hosts worldwide, the guideline addresses the wide array of
      SSTIs that occur in this population. These guidelines emphasize the importance of
      clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and
      administering effective treatments in a timely fashion. 

PMID- 24947531
TI  - Is there a higher risk of CNS adverse events for PI monotherapy versus triple
      therapy? A review of results from randomized clinical trials.
AB  - BACKGROUND: Protease inhibitor (PI) monotherapy for treatment could avoid the
      adverse events, drug resistance, and additional costs associated with other
      antiretrovirals that are normally used, particularly the nucleoside analogues. PI
      monotherapy has mainly been compared with standard triple therapy in randomized
      clinical trials of patients who have HIV RNA suppression at screening and no
      history of virological failure. METHODS: This review included 11 randomized
      clinical trials of darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r)
      monotherapy versus triple therapy in 1,267 patients with HIV RNA suppression at
      baseline who were studied between 48 and 144 weeks. RESULTS: There was no clear
      difference in the risk of central nervous system (CNS) adverse events between PI
      monotherapy (either DRV/r or LPV/r) and standard triple drug treatment. There
      were 2 clinical trials - MONOI (DRV/r) and MOST (LPV/r) - that showed CNS
      symptoms and detectable HIV RNA levels in the cerebrospinal fluid in a small
      number of individuals taking PI monotherapy. CONCLUSIONS: There was no consistent
      evidence from the randomized trials currently available for an additional risk of
      HIV CNS disease during monotherapy with either LPV/r or DRV/r versus standard
      triple drug therapy. However, the information on CNS adverse events has not been
      reported using standardized definitions in the studies. In addition, few
      randomized studies included detailed analysis of neurocognitive function or
      detection of HIV RNA in the cerebrospinal fluid.

PMID- 24947532
TI  - The problem of renal function monitoring in patients treated with the novel
      antiretroviral drugs.
AB  - Chronic kidney disease (CKD) is currently considered a major comorbidity in
      patients affected by HIV infection. In addition, new generation antiretroviral
      drugs that interact with creatinine transporters were recently introduced.
      Rilpivirine, dolutegravir, and cobicistat, with different mechanisms, inhibit the
      amount of tubular secretion of creatinine causing a slight increase in serum
      creatinine levels and consensual eGFRcreat reduction. This will require an
      unprecedented attention to renal issues, because the new drugs can also be
      associated to old antiretroviral drugs that may exert renal toxic effects. Owing
      to the interference of these drugs with creatinine secretion, an alternative way
      of estimating GFR would be desirable. At the moment, methods of direct GFR
      measurement have a high impact on the patient, are not readily available, or are
      not reliable in HIV patients. Consequently, use of classic formulas to estimate
      GFR is still recommended, considering the apparent reduction of eGFRcreat due to
      these drugs. Tubular function needs to be carefully monitored with simple tests
      such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic
      glycosuria, and excretion of uric acid. More specific and sensitive markers of
      tubular damage are still not readily available in all clinical labs. HIV patients
      treated by the novel drugs need to be monitored on a monthly basis for the first
      3 months. Subsequent monitoring should be performed on a quarterly basis or
      guided by comorbidities. 

PMID- 24947533
TI  - Virologic and immunologic responses in treatment-naive patients to ritonavir
      boosted atazanavir or efavirenz with a common backbone.
AB  - BACKGROUND: Atazanavir boosted with ritonavir (ATV/r) and efavirenz (EFV) are
      both recommended as first-line therapies for HIV-infected patients. We compared
      the 2 therapies for virologic efficacy and immune recovery. METHODS: We included
      all treatment-naive patients in the Swiss HIV Cohort Study starting therapy after
      May 2003 with either ATV/r or EFV and a backbone of tenofovir and either
      emtricitabine or lamivudine. We used Cox models to assess time to virologic
      failure and repeated measures models to assess the change in CD4 cell counts over
      time. All models were fit as marginal structural models using both point of
      treatment and censoring weights. Intent-to-treat and various as-treated analyses
      were carried out: In the latter, patients were censored at their last recorded
      measurement if they changed therapy or if they were no longer adherent to
      therapy. RESULTS: Patients starting EFV (n = 1,097) and ATV/r (n = 384) were
      followed for a median of 35 and 37 months, respectively. During follow-up, 51%
      patients on EFV and 33% patients on ATV/r remained adherent and made no change to
      their first-line therapy. Although intent-to-treat analyses suggest virologic
      failure was more likely with ATV/r, there was no evidence for this disadvantage
      in patients who adhered to first-line therapy. Patients starting ATV/r had a
      greater increase in CD4 cell count during the first year of therapy, but this
      advantage disappeared after one year. CONCLUSIONS: In this observational study,
      there was no good evidence of any intrinsic advantage for one therapy over the
      other, consistent with earlier clinical trials. Differences between therapies may
      arise in a clinical setting because of differences in adherence to therapy.

PMID- 24947536
TI  - Characteristics of persistent hyponatremia and tolvaptan treatment in nine
      hospitalized patients with advanced HIV disease.

PMID- 24947535
TI  - Factors associated with study attrition among HIV-infected risky drinkers in St.
      Petersburg, Russia.
AB  - BACKGROUND: Participant attrition in HIV longitudinal studies may introduce bias
      and diminish research quality. The identification of participant characteristics
      that are predictive of attrition might inform retention strategies. OBJECTIVE:
      The study aimed to identify factors associated with attrition among HIV-infected
      Russian risky drinkers from the secondary HIV prevention HERMITAGE trial. We
      examined whether current injection drug use (IDU), binge drinking, depressive
      symptoms, HIV status nondisclosure, stigma, and lifetime history of incarceration
      were predictors of study attrition. We also explored effect modification due to
      gender. METHODS: Complete loss to follow-up (LTFU), defined as no follow-up
      visits after baseline, was the primary outcome, and time to first missed visit
      was the secondary outcome. We used multiple logistic regression models for the
      primary analysis, and Cox proportional hazards models for the secondary analysis.
      RESULTS: Of 660 participants, 101 (15.3%) did not return after baseline. No
      significant associations between independent variables and complete LTFU were
      observed. Current IDU and HIV status nondisclosure were significantly associated
      with time to first missed visit (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.03
      1.87; AHR, 1.38; 95% CI, 1.03-1.86, respectively). Gender stratified analyses
      suggested a larger impact of binge drinking among men and history of
      incarceration among women with time to first missed visit. CONCLUSIONS: Although
      no factors were significantly associated with complete LTFU, current IDU and HIV
      status nondisclosure were significantly associated with time to first missed
      visit in HIV-infected Russian risky drinkers. An understanding of these
      predictors may inform retention efforts in longitudinal studies.

PMID- 24947537
TI  - Economic support to improve tuberculosis treatment outcomes in South Africa: a
      qualitative process evaluation of a cluster randomized controlled trial.
AB  - BACKGROUND: Poverty undermines the adherence of patients to tuberculosis
      treatment. A pragmatic cluster randomized controlled trial was conducted to
      investigate the extent to which economic support in the form of a voucher would
      improve patients' adherence to treatment, and their treatment outcomes. Although
      the trial showed a modest improvement in the treatment success rates of the
      intervention group, this was not statistically significant, due in part to the
      low fidelity to the trial intervention. A qualitative process evaluation,
      conducted in the final few months of the trial, explained some of the factors
      that contributed to this low fidelity. METHODS: In-depth interviews were
      conducted with patients who received vouchers, nurses in intervention clinics,
      personnel in shops who administered the vouchers, and managers of the TB Control
      Programme. These interviews were analyzed thematically. RESULTS: The low fidelity
      to the trial intervention can be explained by two main factors. The first was
      nurses' tendency to 'ration' the vouchers, only giving them to the most needy of
      eligible patients and leaving out those eligible patients whom they felt were
      financially more comfortable. The second was logistical issues related to the
      administration of the voucher as vouchers were not always available for patients
      on their appointed clinic dates, necessitating further visits to the clinics
      which they were not always able to make. CONCLUSIONS: This process evaluation
      identifies some of the most important factors that contributed to the results of
      this pragmatic trial. It highlights the value of process evaluations as tools to
      explain the results of randomized trials and emphasizes the importance of
      implementers as 'street level bureaucrats' who may profoundly affect the way an
      intervention is administered. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN50689131, registered 21 April 2009. The trial protocol is available at the
      following web address: http://www.hst.org.za/publications/study-protocol-economic
      incentives-improving-clinical-outcomes-patients-tb-south-africa.

PMID- 24947534
TI  - Rate, predictors, and consequences of late antenatal booking in a national cohort
      study of pregnant women with HIV in Italy.
AB  - OBJECTIVE: To evaluate the prevalence and consequences of late antenatal booking
      (13 or more weeks gestation) in a national observational study of pregnant women
      with HIV. METHODS: The clinical and demographic characteristics associated with
      late booking were evaluated in univariate analyses using the Mann-Whitney U test
      for quantitative data and the chi-square test for categorical data. The
      associations that were found were re-evaluated in multivariable logistic
      regression models. Main outcomes were preterm delivery, low birthweight,
      nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV
      plasma viral load at third trimester, delivery complications, and gender-adjusted
      and gestational age-adjusted Z scores for birthweight. RESULTS: Rate of late
      booking among 1,643 pregnancies was 32.9%. This condition was associated with
      younger age, African provenance, diagnosis of HIV during pregnancy, and less
      antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm
      delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%,
      P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of
      delivery were more common with late booking (8.2% vs 5.0%, P = .013).
      Multivariable analyses confirmed an independent role of late booking in
      predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7;
      95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8;
      P = .005). CONCLUSIONS: Late antenatal booking was associated with detectable HIV
      RNA in late pregnancy and with complications of delivery. Measures should be
      taken to ensure an earlier entry into antenatal care, particularly for African
      women, and to facilitate access to counselling and antenatal services. These
      measures can significantly improve pregnancy management and reduce morbidity and
      complications in pregnant women with HIV.

PMID- 24947538
TI  - Adaptation and validation of the patient assessment of chronic illness care in
      the French context.
AB  - BACKGROUND: Chronic diseases are major causes of disability worldwide with rising
      prevalence. Most patients suffering from chronic conditions do not always receive
      optimal care. The Chronic Care Model (CCM) has been developed to help general
      practitioners making quality improvements. The Patient Assessment of Chronic
      Illness Care (PACIC) questionnaire was increasingly used in several countries to
      appraise the implementation of the CCM from the patients' perspective. The
      objective of this study was to adapt the PACIC questionnaire in the French
      context and to test the validity of this adaptation in a sample of patients with
      multiple chronic conditions. METHODS: The PACIC was translated into French
      language using a forward/backward procedure. The French version was validated
      using a sample of 150 patients treated for obstructive sleep apnea syndrome
      (OSAS) and having multiple chronic co-morbidities. Several forms of validity were
      analysed: content; face; construct; and internal consistency. The construct
      validity was investigated with an exploratory factorial analysis. RESULTS: The
      French-version of the PACIC consisted in 18 items, after merging two pairs of
      items due to redundancy. The high number of items exhibiting floor/ceiling
      effects and the non-normality of the ratings suggested that a 5-points rating
      scale was somewhat inappropriate to assess the patients' experience of care. The
      construct validity of the French-PACIC was verified and resulted in a bi
      dimensional structure. Overall this structure showed a high level of internal
      consistency. The PACIC score appeared to be significantly related to the age and
      self-reported health of the patients. CONCLUSIONS: A French-version of the PACIC
      questionnaire is now available to evaluate the patients' experience of care and
      to monitor the quality improvements realised by the medical structures. This
      study also pointed out some methodological issues about the PACIC questionnaire,
      related to the format of the rating scale and to the structure of the
      questionnaire.

PMID- 24947539
TI  - Further support for an association between the memory-related gene WWC1 and
      posttraumatic stress disorder: results from the Detroit Neighborhood Health
      Study.

PMID- 24947540
TI  - Response to: further support for an association between the memory-related gene
      WWC1 and posttraumatic stress disorder: results from the Detroit Neighborhood
      Health Study.

PMID- 24947542
TI  - Training practices of hematopoietic progenitor cell-apheresis and -cord blood
      collection staff: analysis of a survey by the Alliance for Harmonisation of
      Cellular Therapy Accreditation.
AB  - BACKGROUND: As hematopoietic stem cell transplantation expands globally,
      identification of the key elements that make up high-quality training programs
      will become more important to optimizing collection practices and quality of the
      products collected. STUDY DESIGN AND METHODS: Multiple-choice and open questions
      to identify training practices of those collecting hematopoietic progenitor cell
      apheresis [HPC(A)] and -cord blood [HPC(CB)] products were distributed via an
      electronic survey tool worldwide. Data were collected on facility demographics,
      job descriptions, and the content of training programs including general
      practices, staff assessment, retraining, and unique program features. RESULTS:
      Respondents from more than 50 countries predominantly associating with facilities
      in North America and Europe represented transplant centers or transfusion
      services also performing collections. For the majority of staff performing HPC(A)
      collections (50%), initial training required as many procedures as necessary be
      done until competency was achieved. Competency was evaluated by direct
      observation comparing performance to written procedures or protocol steps (47%),
      combination of written assessment and observation (45%), evaluation of product
      quality (40%), and written assessment alone (12%). Staff retraining was
      customized on a case-by-case basis (42%). Similar criteria were placed on HPC(CB)
      training, with an emphasis on product quality measured by sterility, CD34+ cell
      collection efficiency, hematocrit, volume, and mononuclear cell count.
      CONCLUSION: Observation, practice, evaluation, and retraining until competency is
      achieved marked the training programs. Success was based on the ability of staff
      to execute procedures ultimately measured in product quality. Identified features
      may assist facilities in further developing and strengthening their own training
      programs.

PMID- 24947543
TI  - Method to increase the yield of eukaryotic membrane protein expression in
      Saccharomyces cerevisiae for structural and functional studies.
AB  - Despite recent successes in the structure determination of eukaryotic membrane
      proteins, the total number of structures of these important proteins is severely
      underrepresented in the Protein Data Bank. Although prokaryotic homologues
      provide valuable mechanistic insight, they often lack crucial details, such as
      post-translational modification and additional intra or extracellular domains
      that are important for understanding the function and regulation of these
      proteins in eukaryotic cells. The production of milligram quantities of
      recombinant protein is still a serious obstacle to the structural and functional
      characterization of these proteins. Here, we report a modification to a
      previously described over expression system using the simple eukaryote
      Saccharomyces cerevisiae that can increase overall protein yield and improve
      downstream purification procedures. Using a metabolic marker under the control of
      a truncated promoter, we show that expression levels for several membrane
      transporters are increased fourfold. We further demonstrate that the increase in
      expression for our test proteins resulted in a concomitant increase in functional
      protein. Using this system, we were able to increase the expression level of a
      plant transporter, NRT1.1, which was a key factor in its structural and
      functional characterization. 

PMID- 24947541
TI  - Reward and affective regulation in depression-prone smokers.
AB  - BACKGROUND: There is a disproportionately high smoking prevalence among
      individuals who are prone to depression. While depression has been conceptualized
      as a disorder of dysregulated positive affect and disrupted reward processing,
      little research has been conducted to determine the role of smoking in these
      processes among depression-prone smokers. METHODS: Depression-prone smokers (DP+;
      n = 34) and smokers not depression-prone (DP-; n = 49) underwent two laboratory
      sessions, one while smoking abstinent and one while smoking ad libitum, to assess
      the relative reinforcing value of smoking and reward sensitivity. Using
      experience sampling methods, participants completed self-report measures of
      subjective reward, positive affect, and negative affect across 3 days while
      smoking as usual and 3 days while smoking abstinent. RESULTS: DP+ were two times
      more likely to work for cigarette puffs versus money in a progressive ratio,
      choice task (odds ratio 2.05; 95% confidence interval 1.04 to 4.06, p = .039)
      compared with DP-. Reward sensitivity as measured by the signal detection task
      did not yield any significant findings. Mixed models regressions revealed a three
      way interaction (depression group, smoking phase, and time) for subjective
      reward, negative affect, and positive affect. For all three of these outcomes,
      the slopes for DP- and DP+ differed significantly from each other (ps < .05) and
      the effect of smoking (versus abstinence) over time was greater for DP+ than DP-
      smokers (ps < .05). CONCLUSIONS: These findings indicate that the effects of
      smoking on reward and positive affect regulation are specific to DP+ smokers and
      highlight novel targets for smoking cessation treatment in this population.

PMID- 24947544
TI  - Sperm DNA integrity testing: big halo is a good predictor of embryo quality and
      pregnancy after conventional IVF.
AB  - Sperm DNA integrity is a sperm functional parameter of male fertility evaluation.
      Two parameters of sperm DNA integrity were observed: DNA damage expressed as DNA
      fragmentation index (DFI) and percentage of the DNA undamaged spermatozoa
      expressed as big halo. Halosperm test was used for sperm DNA integrity
      determination. The aim of this study was to evaluate which DNA integrity
      parameter is better as an embryo quality and pregnancy prognostic parameter after
      the conventional IVF. We evaluated two embryo groups (positive and negative
      group) according to the 3rd day cumulative embryo score. Big halo and DFI, as we
      expected, showed good correlation (r = -0.69; p < 0.001). Receiver operating
      characteristic (ROC) analyses show that DFI and big halo are significant (p <
      0.001) as prognostic parameters of embryo quality. ROC curves comparison of DFI
      and big halo revealed the AUC value for big halo to be significantly higher (DFI
      AUC = 0.71 vs. big halo AUC = 0.83; p = 0.025) than for DFI. Big halo was found
      to be the only independent predictor of embryo quality. Sperm DNA integrity both
      parameters are good prognostic parameters of embryo quality after the
      conventional IVF where big halo seems to be better. ROC analyses show DFI and big
      halo as significant prognostic parameters for achieved pregnancy (AUC +/- SE for
      DFI was 0.67 +/- 0.06 and 0.75 +/- 0.06 for big halo). To our knowledge, this is
      the first study demonstrating the correlation between sperm DNA undamaged rate
      expressed as big halo parameter and semen characteristics as well as the
      influence on fertilization rate, embryo quality and pregnancy in conventional
      IVF.

PMID- 24947545
TI  - The recent progresses on the improved therapy of melanoma by novel drug delivery
      systems.
AB  - Melanoma is a life threatening disease with a growing incidence rate. It is
      estimated that 9840 patients will die from melanoma in 2014. Despite numerous
      attempts for treating metastatic melanoma, conventional therapies including
      systemic chemotherapy or immunotherapy, either as single agents or combined, have
      not been promising. The most cytotoxic agents have low molecular weight, which
      leads to rapid excretion, nonspecific distribution, and poor therapeutic index.
      Therefore, they may even increase toxicity due to their non-specific action on
      healthy tissue that can exacerbate the malady. To provide optimum effective
      concentration, multiple-dose drug administration is required, which again can
      increase the incidence of adverse effects. Recent developments in drug delivery
      systems are able to improve the drug efficacy and safety, and offer more
      promising approaches in treating melanoma. Recent researches have shed more light
      on the advantages of novel drug loaded carrier systems versus free drugs. Most of
      these animal studies, reported improvement in treatment efficacy and survival
      rate using novel carrier systems. This is related to the ability of these systems
      in enhancing the anticancer effect by modifying drug pharmacokinetics and
      biodistribution, selective target delivery of the agents to the diseased tissue
      and their ability to cross the biological barriers. In this paper, it is
      attempted to illustrate the potentials of novel strategies in treatment of
      melanoma incorporating drug delivery systems versus conventional therapies. 

PMID- 24947547
TI  - Analysis of the ganglion cell layer and photoreceptor layer using optical
      coherence tomography after idiopathic epiretinal membrane surgery.
AB  - PURPOSE: To investigate the correlation of visual acuity with the ganglion cell
      layer and the photoreceptor layer using spectral-domain optical coherence
      tomography after surgery for idiopathic epiretinal membrane (ERM). METHODS: The
      medical records of 58 eyes were reviewed retrospectively to collect data on
      visual acuity (VA), ganglion cell complex thickness (GT) and photoreceptor
      reflectivity (PR) at baseline, 3 months, and 6 months after surgery. The GT was
      adjusted to compensate for tractional thickening by calculating the proportional
      thickness to the macular thickness (MT). The PR was adjusted to compensate for
      the shadowing effects from the inner retina, which was achieved by calculating
      the ratio to the retinal pigment epithelium reflectivity (RR). The relative GT
      (RGT = GT/MT) and relative PR (RPR = PR/RR) were analyzed to determine their
      correlation with visual acuity. RESULTS: The GT was segmented correctly in 13
      eyes at baseline, and in all eyes after surgery. The RGT and RPR were
      significantly lower than the normal eye. Thinner RGT correlated with poorer VA at
      3 months (R = -0.352, p = 0.007) and 6 months (R = -0.324, p = 0.013), but the
      RPR had correlation with visual acuity only at 6 months (R = -0.377, p = 0.004).
      The area under the receiver operating characteristic curve was significant for VA
      >= 20/30 in both the RGT and RPR, and this significance was present for visual
      acuity >= 0/25 only in the RGT. CONCLUSIONS: The postoperative ganglion cell
      layer was found to be correlated to postoperative VA more consistently than the
      photoreceptor layer after ERM surgery. The outer retinal damage was a determining
      factor in the poor VA group.

PMID- 24947546
TI  - Travelers with sickle cell disease.
AB  - BACKGROUND: Sickle cell disease (SCD) is the most common genetic disease among
      persons with African ancestry. This article provides a background to SCD and
      reviews many important aspects of travel preparation in this population. METHODS:
      The medical literature was searched for studies on travel-associated preparedness
      and complications in individuals with SCD. Topics researched included malaria,
      bacterial infections, vaccinations, dehydration, altitude, air travel, and travel
      preparedness. RESULTS: There is very little published literature that
      specifically addresses the risks faced by travelers with SCD. Rates of medical
      complications during travel appear to be high. There is a body of literature that
      describes complications of SCD in indigenous populations, particularly within
      Africa. The generalizability of these data to a traveler is uncertain. Combining
      these sources of data and the broader medical literature, we address major travel
      related questions that may face a provider preparing an individual with SCD for
      safe travel. CONCLUSIONS: Travelers with SCD face considerable medical risks when
      traveling to developing tropical countries, including malaria, bacterial
      infections, hypovolemia, and sickle cell-associated vaso-occlusive crises. For
      individuals with SCD, frank counseling about the risks, vigilant preventative
      measures, and contingency planning for illness while abroad are necessary aspects
      of the pre-travel visit.

PMID- 24947548
TI  - Hydrophobic acrylic versus polymethyl methacrylate intraocular lens implantation
      following cataract surgery in the first year of life.
AB  - PURPOSE: To evaluate complication rates following implantation of hydrophobic
      acrylic versus polymethyl methacrylate (PMMA) intraocular lens (IOL) with
      cataract surgery in infants. METHODS: Records of children undergoing cataract
      surgery with IOL implantation in first year of life were retrospectively
      reviewed. Infants were divided into two groups--hydrophobic acrylic IOLs were
      implanted in group A, and PMMA IOLs in group B. Outcome measures included
      incidence of complications, additional surgical procedures, and refractive error
      changes. RESULTS: One hundred and thirteen eyes of 113 children (75 males) with
      mean age of 6.49 +/- 3.56 months were included. Group A included 62 eyes, and
      group B included 51 eyes. The two groups did not differ significantly in terms of
      age and axial length. There was no significant difference between the groups for
      incidence of posterior capsular opacification (PCO), pupillary membranes,
      glaucoma, fibrin on IOL surface or IOL malposition (p = 0.09). Development of PCO
      was delayed in group A (p = 0.049). Thirteen eyes of group A and 18 eyes of group
      B required additional surgical intervention (p = 0.20) in the follow-up visits.
      CONCLUSION: Comparable complications may be expected in infants with PMMA and
      hydrophobic acrylic lenses. Children implanted with PMMA IOLs may require earlier
      surgical re-intervention for PCO.

PMID- 24947549
TI  - Orbicularis oculi muscle transposition for repairing involutional lower eyelid
      entropion.
AB  - PURPOSE: To describe a simple technique for involutional entropion correction and
      to present the findings of a retrospective interventional case series study.
      METHODS: We studied a consecutive series of 414 patients (609 eyelids). Patients
      presenting with involutional entropion in the absence of lateral canthal tendon
      laxity underwent orbicularis oculi muscle (OOM) transposition from pretarsal
      position to corresponding preseptum without horizontal shortening or resection of
      the orbicularis muscle. RESULTS: Immediate resolution of entropion and associated
      ocular symptoms was achieved in 607 eyelids (99.67 %). An early postoperative
      complication was localized lid swelling that gradually subsided within one week.
      Over-correction occurred in six cases and resolved with pressure dressing, mostly
      one or two days post-operation. At final follow-up, a significant improvement in
      eyelid position was achieved in 579 eyelids (95.07 % ). There was mild recurrence
      of entropion in 30 eyelids (4.93 %). The mean follow-up was 6.84 months (range, 6
      12 months). CONCLUSIONS: Orbicularis oculi muscle transposition is a reasonably
      successful procedure with a high success rate, and is particularly suitable for
      patients for whom there exits overriding of the preseptal OOM over the pretarsal
      OOM.

PMID- 24947550
TI  - Selective endothelin inhibition in diabetic nephropathy: is it the icing on the
      cake?

PMID- 24947551
TI  - Citizen participation and discontent in three Southern European health systems.
AB  - Participation has featured in political agendas in recent decades and the domain
      of healthcare has not been indifferent to its appeal. Although emerging later
      than in other European regions, the involvement of civil society in healthcare
      decision-making procedures has proved one of the biggest challenges facing
      Southern European health systems. The health systems of the countries considered
      in this analysis - Italy, Portugal and Spain - underwent reforms that brought
      citizen participation to the forefront of the health system. Through national
      laws or health plans, each of these countries has recognised the need to promote
      participation in order to 'give a voice' to citizens in the health sector.
      Accordingly, a range of significant activities have been implemented in the
      region, although they have been developed unequally within national territories,
      at different paces and involving the mobilisation of different actors. This
      article focuses on the most relevant experiences of citizen participation
      designed and implemented in the three selected countries, describing their key
      features and potential, as well as the main critical issues and contradictions
      that have emerged over time. Particular emphasis is given to the impact of the
      current financial crisis on Southern European national health systems, especially
      in terms of participatory methods, the way in which citizen participation is
      progressing and civil society's reaction to these important changes.

PMID- 24947553
TI  - Glassy states and super-relaxation in populations of coupled phase oscillators.
AB  - Large networks of coupled oscillators appear in many branches of science, so that
      the kinds of phenomena they exhibit are not only of intrinsic interest but also
      of very wide importance. In 1975, Kuramoto proposed an analytically tractable
      model to describe these systems, which has since been successfully applied in
      many contexts and remains a subject of intensive research. Some related problems,
      however, remain unclarified for decades, such as the existence and properties of
      the oscillator glass state. Here we present a detailed analysis of a very general
      form of the Kuramoto model. In particular, we find the conditions when it can
      exhibit glassy behaviour, which represents a kind of synchronous disorder in the
      present case. Furthermore, we discover a new and intriguing phenomenon that we
      refer to as super-relaxation where the oscillators feel no interaction at all
      while relaxing to incoherence. Our findings offer the possibility of creating
      glassy states and observing super-relaxation in real systems. 

PMID- 24947552
TI  - Solidarity by demand? Exit and voice in international medical travel - the case
      of Indonesia.
AB  - Globally, more patients are intentionally travelling abroad as consumers for
      medical care. However, while scholars have begun to examine international medical
      travel's (IMT) impacts on the people and places that receive medical travellers,
      study of its impacts on medical travellers' home contexts has been negligible and
      largely speculative. While proponents praise IMT's potential to make home health
      systems more responsive to the needs of market-savvy healthcare consumers,
      critics identify it as a way to further de-politicise the satisfaction of
      healthcare needs. This article draws from work on political consumerism, health
      advocacy and social movements to argue for a reframing of IMT not as a 'one-off'
      statement about or an event external to struggles over access, rights and
      recognition within medical travellers' home health systems but rather as one of a
      range of critical forms of on-going engagement embedded within these struggles.
      To do this, the limited extant empirical work addressing domestic impacts of IMT
      is reviewed and a case study of Indonesian medical travel to Malaysia is
      presented. The case study material draws from 85 interviews undertaken in 2007-08
      and 2012 with Indonesian and Malaysian respondents involved in IMT as care
      recipients, formal and informal care-providers, intermediaries, promoters and
      policy-makers. Evidence from the review and case study suggests that IMT may
      effect political and social change within medical travellers' home contexts at
      micro and macro levels by altering the perspectives, habits, expectations and
      accountability of, and complicity among, medical travellers, their families,
      communities, formal and informal intermediaries, and medical providers both
      within and beyond the container of the nation-state. Impacts are conditioned by
      the ideological foundations underpinning home political and social systems, the
      status of a medical traveller's ailment or therapy, and the existence of
      organised support for recognition and management of these in the home context. 

PMID- 24947554
TI  - The surface chemistry of NO(x) on mackinawite (FeS) surfaces: a DFT-D2 study.
AB  - We present density functional theory calculations with a correction for the long
      range interactions (DFT-D2) of the bulk and surfaces of mackinawite (FeS), and
      subsequent adsorption and dissociation of NO(x) gases (nitrogen monoxide (NO) and
      nitrogen dioxide (NO2)). Our results show that these environmentally important
      molecules interact very weakly with the energetically most stable (001) surface,
      but adsorb relatively strongly onto the FeS(011), (100) and (111) surfaces,
      preferentially at Fe sites via charge donation from these surface species. The
      NOx species exhibit a variety of adsorption geometries, with the most favourable
      for NO being the monodentate Fe-NO configuration, whereas NO2 is calculated to
      form a bidentate Fe-NOO-Fe configuration. From our calculated thermochemical
      energy and activation energy barriers for the direct dissociation of NO and NO2
      on the FeS surfaces, we show that NO prefers molecular adsorption, while
      dissociative adsorption, i.e. NO2 (ads) -> [NO(ads) + O(ads)] is preferred over
      molecular adsorption for NO2 onto the mackinawite surfaces. However, the
      calculated high activation barriers for the further dissociation of the second N
      O bond to produce either [N(ads) and 2O(ads)] or [N(ads) and O2(ads)] suggest
      that complete dissociation of NO2 is unlikely to occur on the mackinawite
      surfaces.

PMID- 24947556
TI  - Do North Atlantic eels show parallel patterns of spatially varying selection?
AB  - BACKGROUND: The two North Atlantic eel species, the European and the American
      eel, represent an ideal system in which to study parallel selection patterns due
      to their sister species status and the presence of ongoing gene flow. A panel of
      80 coding-gene SNPs previously analyzed in American eel was used to genotype
      European eel individuals (glass eels) from 8 sampling locations across the
      species distribution. We tested for single-generation signatures of spatially
      varying selection in European eel by searching for elevated genetic
      differentiation using FST-based outlier tests and by testing for significant
      associations between allele frequencies and environmental variables. RESULTS: We
      found signatures of possible selection at a total of 11 coding-gene SNPs.
      Candidate genes for local selection constituted mainly genes with a major role in
      metabolism as well as defense genes. Contrary to what has been found for American
      eel, only 2 SNPs in our study correlated with differences in temperature, which
      suggests that other explanatory variables may play a role. None of the genes
      found to be associated with explanatory variables in European eel showed any
      correlations with environmental factors in the previous study in American eel.
      CONCLUSIONS: The different signatures of selection between species could be due
      to distinct selective pressures associated with the much longer larval migration
      for European eel relative to American eel. The lack of parallel selection in
      North Atlantic eels could also be due to most phenotypic traits being polygenic,
      thus reducing the likelihood of selection acting on the same genes in both
      species.

PMID- 24947555
TI  - HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma
      in Malaysian Chinese.
AB  - Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the
      nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1)
      infection. We carried out a genome-wide association study (GWAS) of 575,247
      autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese
      ethnicity. Potential association signals were replicated in a separate cohort of
      260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A
      to NPC with the strongest signal detected in rs3869062 (p = 1.73 * 10(-9)). HLA-A
      fine mapping revealed associations in the amino acid variants as well as its
      corresponding SNPs in the antigen peptide binding groove (p(HLA-A-aa-site-99) =
      3.79 * 10(-8), p(rs1136697) = 3.79 * 10(-8)) and T-cell receptor binding site
      (p(HLA-A-aa-site-145) = 1.41 * 10(-4), p(rs1059520) = 1.41 * 10(-4)) of the HLA
      A. We also detected strong association signals in the 5'-UTR region with
      predicted active promoter states (p(rs41545520) = 7.91 * 10(-8)). SNP rs41545520
      is a potential binding site for repressor ATF3, with increased binding affinity
      for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic
      regression diminished the effects of HLA-A amino acid variants and SNPs,
      indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent
      HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC
      susceptibility in the Malaysian Chinese.

PMID- 24947557
TI  - Effectiveness of a pilot intervention to reduce abciximab-related bleeding in
      patients with acute coronary syndromes.
AB  - BACKGROUND AND OBJECTIVE: Reducing bleeding events is a priority in patients
      diagnosed with acute coronary syndromes (ACS). The effectiveness of optimization
      measures for reducing abciximab-related bleeding was evaluated through the
      implementation of a pilot program developed by the Pharmacy and the Cardiology
      Departments at a tertiary-care hospital. MAIN OUTCOME MEASURE: Percentage of
      bleeding events. RESULTS: Intervention was effective in reducing the incidence of
      the three factors associated with an increased risk of bleeding between the pre
      intervention phase (n = 86) and the post-intervention phase (n = 73): unknown
      body weight (24.4 vs. 1.4 %, p = 0.0001), overdosing (31.4 vs. 0 %, p < 0.0001)
      and combination with bivalirudin (12.8 vs. 1.4 %, p = 0.016). Bleeding events
      associated with these factors were numerically reduced in all three cases but
      these differences were not statistically significant between both periods.
      CONCLUSION: The implementation of a multidisciplinary prevention program can
      reduce situations associated with an increased risk of bleeding in patients
      treated with abciximab. Larger scale trials are needed to confirm whether such
      programs can also reduce the incidence of bleeding at a statistically significant
      level.

PMID- 24947558
TI  - Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic
      drugs from multilayered polymeric microparticles.
AB  - First-line cancer chemotherapy necessitates high parenteral dosage and repeated
      dosing of a combination of drugs over a prolonged period. Current commercially
      available chemotherapeutic agents, such as Doxil and Taxol, are only capable of
      delivering single drug in a bolus dose. The aim of this study is to develop dual
      drug-loaded, multilayered microparticles and to investigate their antitumor
      efficacy compared with single-drug-loaded particles. Results show hydrophilic
      doxorubicin HCl (DOX) and hydrophobic paclitaxel (PTX) localized in the poly(dl
      lactic-co-glycolic acid, 50:50) (PLGA) shell and in the poly(l-lactic acid)
      (PLLA) core, respectively. The introduction of poly[(1,6-bis-carboxyphenoxy)
      hexane] (PCPH) into PLGA/PLLA microparticles causes PTX to be localized in the
      PLLA and PCPH mid-layers, whereas DOX is found in both the PLGA shell and core.
      PLGA/PLLA/PCPH microparticles with denser shells allow better control of DOX
      release. A delayed release of PTX is observed with the addition of PCPH. Three
      dimensional MCF-7 spheroid studies demonstrate that controlled co-delivery of DOX
      and PTX from multilayered microparticles produces a greater reduction in spheroid
      growth rate compared with single-drug-loaded particles. This study provides
      mechanistic insights into how distinctive structure of multilayered
      microparticles can be designed to modulate the release profiles of anticancer
      drugs, and how co-delivery can potentially provide better antitumor response. 

PMID- 24947559
TI  - Surrogacy assessment using principal stratification and a Gaussian copula model.
AB  - In clinical trials, a surrogate outcome ( S) can be measured before the outcome
      of interest ( T) and may provide early information regarding the treatment ( Z)
      effect on T. Many methods of surrogacy validation rely on models for the
      conditional distribution of T given Z and S. However, S is a post-randomization
      variable, and unobserved, simultaneous predictors of S and T may exist, resulting
      in a non-causal interpretation. Frangakis and Rubin developed the concept of
      principal surrogacy, stratifying on the joint distribution of the surrogate
      marker under treatment and control to assess the association between the causal
      effects of treatment on the marker and the causal effects of treatment on the
      clinical outcome. Working within the principal surrogacy framework, we address
      the scenario of an ordinal categorical variable as a surrogate for a censored
      failure time true endpoint. A Gaussian copula model is used to model the joint
      distribution of the potential outcomes of T, given the potential outcomes of S.
      Because the proposed model cannot be fully identified from the data, we use a
      Bayesian estimation approach with prior distributions consistent with reasonable
      assumptions in the surrogacy assessment setting. The method is applied to data
      from a colorectal cancer clinical trial, previously analyzed by Burzykowski et
      al.

PMID- 24947560
TI  - Effect of non-native helix destabilization on the folding of equine beta
      lactoglobulin.
AB  - beta-lactoglobulin forms a non-native alpha-helix during an early stage of
      folding. To address the role of the non-native structure in the folding process,
      we designed several mutants of equine beta-lactoglobulin with reduced helical
      propensity in the non-native helix region. One of them, A123T, showed a similar
      structure to that of the wild-type protein; its folding kinetics was investigated
      by stopped-flow circular dichroism (CD) and fluorescence. Although A123T showed a
      reduced burst-phase CD intensity, its folding rate was similar to that of the
      wild-type protein, which indicated that the formation of the non-native helix
      does not accelerate or decelerate the folding reaction. 

PMID- 24947561
TI  - High-throughput production of two disulphide-bridge toxins.
AB  - A quick and efficient production method compatible with high-throughput screening
      was developed using 36 toxins belonging to four different families of two
      disulphide-bridge toxins. Final toxins were characterized using HPLC co-elution,
      CD and pharmacological studies. 

PMID- 24947562
TI  - Dam methylation regulates the expression of SPI-5-encoded sopB gene in Salmonella
      enterica serovar Typhimurium.
AB  - DNA adenine methylation is an essential factor in Salmonella virulence. Here, we
      investigate the involvement of DNA adenine methylase (Dam) in the expression and
      translocation of a SPI-5-encoded effector of S. Typhimurium. SopB expression and
      secretion were determined using SopB-FLAG-tagged wild type and dam strains of S.
      Typhimurium. Western blot and quantitative reverse transcriptase PCR analysis
      showed that the dam mutant expresses lower levels of SopB protein and sopB mRNA
      than the wild type strain under SPI-1 and SPI-2 inducing conditions in vitro.
      SopB secretion was also considerably impaired in the absence of dam. In agreement
      with in vitro experiments, SopB synthesis in dam mutants recovered from infected
      epithelial cells and from murine mesenteric lymph nodes was reduced by 40%
      respect to the wild type strain (p < 0.05). SopB translocation was neither
      detected in the cytosol of epithelial cells nor in the cytosol of cells isolated
      from mesenteric lymph nodes infected with the dam mutant. Taken together, our
      results demonstrate that, in S. Typhimurium, Dam methylation modulates the
      expression and translocation of SPI-5-encoded SopB effector.

PMID- 24947563
TI  - Effects of supplemental nanoparticle trivalent chromium on the nutrient
      utilization, growth performance and serum traits of broilers.
AB  - The aim of this study was to investigate the effect of dietary supplementation of
      nanoparticle trivalent chromium on nutrient utilization, growth performance and
      serum traits of broilers. This study included two trials. In trial 1, 32 three
      week-old broilers were divided into four groups: the control, chromium chloride
      (CrCl3), chromium picolinate (CrPic) and nanoparticle chromium picolinate
      (NanoCrPic). Chromium was added at a 1200 MUg/kg level to evaluate the nutrient
      and chromium utilization. In trial 2, 160 one-day-old broilers were randomly
      divided into four groups as in trial 1, with four replicates. The results of
      trial 1 indicated that the chromium utilization is as follows: NanoCrPic > CrPic
      > CrCl3 and control groups, with significant differences between groups (p <
      0.05). Crude fat utilization in CrCl3 group was lower than in that the control
      group (p < 0.05). The results of trial 2 indicated that feed intake of 4-5 weeks
      showed better result in the CrCl3 group than that in the CrPic group (p < 0.05).
      The results of serum traits indicated that the LDL-cholesterol in the NanoCrPic
      groups was lower than that in the CrPic group (p < 0.05). The NanoCrpic and CrPic
      groups showed significantly increased serum chromium concentration when compared
      with the control and CrCl3 groups; the triglyceride level in the CrCl3 group was
      lower than that in the CrPic group (p < 0.05). This study concluded that compared
      with CrPic, NanoCrpic supplementation could increase chromium utilization and
      lower the serum LDL-cholesterol of broilers.

PMID- 24947565
TI  - Disability language in the Disability and Health Journal.

PMID- 24947566
TI  - Political participation as a disability rights issue.

PMID- 24947564
TI  - The analysis of ascending aortic dilatation in patients with a bicuspid aortic
      valve using the ratio of the diameters of the ascending and descending aorta.
AB  - BACKGROUND: A bicuspid aortic valve (BAV) is associated with premature valve
      dysfunction and abnormalities of the ascending aorta. The aim of our study was to
      assess the degree of ascending aortic dilatation by measuring the ratio of the
      dimension of the AAo to that of the descending aorta (DAo) using preoperative
      computerized tomography (CT). METHODS: A review of our institutional clinical
      database identified 76 patients undergoing aortic valve replacement (AVR) and 73
      control patients undergoing off-pump coronary artery bypass (OPCAB group) between
      September 2009 and April 2012. RESULTS: There were 17 patients diagnosed with BAV
      (BAV group), and the remaining 59 patients had a tricuspid aortic valve (TAV
      group). The ratios of the dimensions of the AAo to that of the DAo (AAo/DAo) for
      each group were: BAV, 1.58 +/- 0.25; TAV, 1.32 +/- 0.11; and OPCAB, 1.29 +/-
      0.12. Interestingly, the AAo/DAo of the BAV group was significantly larger than
      that of the other groups. CONCLUSIONS: Although progressive AAo dilatation for
      BAV is well documented, the diameter of the AAo is currently the only estimate of
      aortic dilatation. In this study, we report that the ratio of the AAo and DAo
      diameters in patients with BAV can be a new index for assessing the dilatation of
      the AAo and differentiating the patients with BAV from those with TAV.

PMID- 24947567
TI  - The neglected burden of caregiving in low- and middle-income countries.
AB  - BACKGROUND: The number of persons with disability worldwide is estimated at more
      than one billion, and low- and middle-income countries (LMIC's) have particularly
      high prevalence. The consequences of disability have garnered growing attention,
      but the burden of caregiving for persons with disease or disability remains
      largely unquantified especially in LMIC's. OBJECTIVE: The goal of this paper is
      to report the results of a review of literature on caregiving in LMIC's,
      describing the characteristics of caregivers and of persons with disease or
      disability for whom care is provided, and the burden of caregiving in several
      domains. METHODS: We reviewed electronically available literature up to March
      2012. Data were extracted pertaining to the following categories: caregiver
      demographics, caregiving activities, psychological burden, social burden,
      financial burden, physical burden, and time burden. RESULTS: Our review
      demonstrates that there is considerable and neglected burden on caregivers in
      LMIC's in physical, psychological, social, time, and financial realms. Existing
      literature is limited by the small volume of published research available on this
      topic, diverse methodologies, and lack of consensus on how to define and measure
      caregiver burden. However the evidence is clear that there are adverse
      consequences that arise as a result of the role of caregiver in this setting.
      CONCLUSIONS: In light of the mounting evidence of the significant burden placed
      on caregivers of persons with disease and disability, it is imperative that the
      opportunity be taken to ensure that evidence informs best practice and policy in
      order to provide the support and services necessary to make an impact.

PMID- 24947568
TI  - What is the evidence of the experience of having a fall across the life course? A
      qualitative synthesis.
AB  - BACKGROUND: Alleviating the economic and human impacts of falls and fear of
      falling are critical health and social care issues. Despite some proven
      effectiveness of a number of falls prevention intervention programmes, uptake
      remains low and attrition high. There is a need for greater understanding of
      social, cultural and individual, life course positioning of falling, actual or
      perceived. OBJECTIVE: To address the question: what is the evidence of the
      experience of having a fall across the life course? METHOD: A qualitative
      evidence synthesis with key electronic databases searched from 1990 to 2011 using
      terms related to the experience of falls and falling. Selected papers presented
      data from the perspective of the person who had fallen. Synthesis included
      collaborative coding of 'incidents' related to falling, theoretical sampling of
      studies to challenge emerging theories, and constant comparison of categories to
      generate explanations. RESULTS: The initial focus was to access and assess the
      evidence for the experiences of a fall across the life course but the authors'
      systematic search revealed that the vast majority of the published literature
      focuses on the experience of a fall in later life. Only 2 of the 16 studies
      included, provided perspectives of falling from a life stage other than that of
      older adults. However older adults' perceptions of their falls experiences are
      likely to be influenced by lifelong attitudes and beliefs about falling and older
      age. Synthesis identified that a falls incident or fear of falling induces
      explicit or implicit 'Fear.' Consequences are related to notions of 'Control' and
      'Social standing.' Recovery work involves 'Adaptation,' 'Implications,' 'Social
      standing' and 'Control.' 'Explanation' is sought. CONCLUSIONS: How and why people
      make sense of falling across the life course should have positive impacts on
      developing falls intervention programmes that people will want to engage with and
      adhere to.

PMID- 24947569
TI  - Disability and voting.
AB  - BACKGROUND: For millions of people with disabilities in the United States,
      exercising the fundamental right to vote remains a challenge. Over the last few
      decades, the U.S. government has enacted several pieces of legislation to make
      voting accessible to individuals with disabilities. OBJECTIVE: We examine trends
      in self-reported voting rates among people with and without disabilities to
      uncover evidence for the effects of these policies on political participation. We
      also explore what policy change is necessary to encourage people with
      disabilities to vote by investigating whether the participation rates vary by the
      types of disabilities. METHODS: We analyze the Current Population Survey (CPS)
      data in the years of presidential elections for the period of 1980-2008. RESULTS:
      Our analysis shows that the population aged 18-64 with work-preventing
      disabilities has been persistently less likely to vote compared to the
      corresponding population without such disabilities. In addition, individuals with
      cognitive and mobility impairments have the lowest rates of electoral
      participation. The gap in the likelihood of voting in-person between people with
      and without disabilities is considerably larger than the gap in the likelihood of
      voting by-mail, regardless of the types of impairments that they have.
      CONCLUSIONS: The participation gap between people with and without disabilities
      did not decrease over the last three decades despite the presence of federal laws
      that aimed at removing barriers for voting.

PMID- 24947571
TI  - Physical activity in persons with late effects of polio: a descriptive study.
AB  - BACKGROUND: To promote a healthy and active lifestyle there is a need to increase
      our knowledge of the level of physical activity (PA) among people with late
      effects of polio. OBJECTIVES: To examine PA in people with late effects of polio
      and to assess the relationship between PA, life satisfaction and various
      sociodemographic factors. METHODS: PA was assessed in 81 persons with late
      effects of polio using the Physical Activity and Disability Survey (PADS) and by
      a pedometer. Life satisfaction was assessed with the Life Satisfaction
      Questionnaire (LiSat-11). RESULTS: The amount of PA varied considerably but on
      average the participants were physically active almost 3 h per day, mostly in
      household activities. The mean value of the pedometer counts was 6212 steps per
      day (SD = 3208). Sixty-nine percent of the participants rated themselves as
      satisfied with life as a whole. The sum of PADS was positively and significantly
      related to the number of steps (r = 0.39, p < 0.001), increasing age (r = 0.26, p
      < 0.05) and to the level of global satisfaction with life (rho = 0.23, p < 0.05).
      The number of steps was also positively and significantly associated with level
      of global satisfaction with life (rho = 0.37, p < 0.001). CONCLUSION: Despite a
      progressive physical disability, people with late effects of polio are physically
      active, but much of the activities are performed as part of their household
      activities and not as traditional exercise. The relationship between PA, life
      satisfaction and age further supports the general contention that an active
      lifestyle is an important factor for perceived well-being among older people.

PMID- 24947570
TI  - Development of an audio-computer assisted self-interview to investigate violence
      and health in the lives of adults with developmental disabilities.
AB  - BACKGROUND: Audio computer-assisted self-interviews (ACASIs) have safely and
      effectively obtained sensitive research data from the general public and have
      been recommended for use with people with disabilities. However, few studies have
      used ACASIs with people with disabilities and ACASIs have not been used to
      investigate the relationship between disability, interpersonal violence (IPV),
      and physical and psychological health among people with developmental
      disabilities (PWDD). OBJECTIVE: We developed an accessible ACASI specifically
      designed to allow PWDD to answer questions independently, while privately and
      securely collecting anonymous data related to their disability, IPV experiences,
      and physical and psychological health. METHODS: We used a safety protocol to
      apply community based participatory research (CBPR) principles and an iterative
      process to create, test, and administer a cross-sectional ACASI survey to 350
      adults with developmental disabilities in urban and rural locales. RESULTS: Most
      participants completed the ACASI independently and reported that its
      accessibility features allowed them to do so. Most also agreed that the ACASI was
      easy to use, its questions were easy to understand, and that they would prefer
      using an ACASI to answer IPV and health-related questions rather than in a face
      to-face interview. The majority agreed that health and safety were critical
      issues to address. CONCLUSIONS: ACASI technology has the potential to maximize
      the independent and private participation of PWDD in research on sensitive
      topics. We recommend further exploration into accessibility options for ACASI
      technology, including hardware and Internet applications.

PMID- 24947572
TI  - Calibration and validation of the Physical Activity Barrier Scale for persons who
      are blind or visually impaired.
AB  - BACKGROUND: It is critical to employ accurate measures when assessing physical
      activity (PA) barriers in any subpopulation, yet existing measures are not
      appropriate for persons with blindness or visual impairment (PBVI) due to a lack
      of validity or reliability evidence. OBJECTIVE: To develop and calibrate a PA
      barrier scale for PBVI. METHODS: An expert panel (n = 3) and 18 PBVI were
      recruited to establish content validity for a PA barriers subscale; 160 PBVI (96
      females) completed the scale along with the Physical Activity Scale for
      Individuals with Physical Disabilities for calibration. To establish construct
      related validity evidence, Confirmative factor analysis (CFA) and Rasch analysis
      were applied. To investigate internal consistency and reliability, Cronbach's
      alpha and the reliability coefficient (R) were employed, respectively. RESULTS:
      Following CFA and Rasch analyses, five items were eliminated due to misfits;
      reliability coefficients were unchanged upon deletion of these items. The
      barriers perceived by PBVI to have the most negative impact on PA included "lack
      of self-discipline" (logit = 1.40) and "lack of motivation" (logit = 1.27). "Too
      many stairs in the exercise facility" (logit = -1.49) was perceived to have the
      least impact. CONCLUSIONS: The newly-developed scale was found to be a valid and
      reliable tool for evaluating PA barriers in PBVI. To enhance promotion of health
      producing levels of PA in PBVI, practitioners should consider applying this new
      tool as a precursor to programs aimed at improving PA participation in this
      group.

PMID- 24947573
TI  - Prevalence of physical activity, screen time, and obesity among US children by
      the service type of special health care needs.
AB  - BACKGROUND: Children with special health care needs (SHCN) may be at greater risk
      of obesity than children without SHCN. A new classification system categorizes
      SHCN among children by service type using the following categories: No-SHCN,
      medication use only, services use only, medication + service use, and functional
      limitations. Research is needed to examine obesity and obesity-related behaviors
      among children using the new classification system. OBJECTIVE: To determine the
      prevalence of inadequate vigorous physical activity (VPA), high screen time and
      obesity by SHCN category using the new classification system. METHODS:
      Multivariate regression models were fitted for inadequate VPA, high screen time,
      and obesity to determine if there were differences in these outcomes by SHCN
      category, adjusting for multistage-sampling and survey-design effects using a
      nationally representative sample of children in the National Survey of Children's
      Health 2007. RESULTS: 22.9% of the sample was classified as having SHCN: 9%
      medication use only, 5% medication + service use, 4% service use only, and 5%
      functional limitations. Children in the medication use only and medication +
      service use groups were not at increased risk for inadequate VPA, high screen
      time, or obesity. Children in the service use only and functional limitation
      groups had increased odds of high screen time and obesity, which disappeared
      after controlling for confounders. However, the higher odds of inadequate VPA
      remained significant in the service use only [OR (95% CI) = 2.00 (1.34-3.00)] and
      the functional limitations groups with 2.21 (1.55-3.15). CONCLUSIONS: Physical
      activity promotion programs are needed for children with SHCN, especially
      children with functional limitations and those who require service use only and
      do not use prescribed medication.

PMID- 24947574
TI  - Disability and sleep duration: evidence from the American Time Use Survey.
AB  - BACKGROUND: Regular short and long sleep durations are associated with increased
      mortality and morbidity. While previous research shows significant sleep
      disparities between people with and without disabilities, less is known about the
      association between different types of disability and high-risk sleep using
      nationally representative data. OBJECTIVE: We examine the association between
      short and long sleep durations and having a work disability or an impairment in
      sensory, cognitive, or physical functioning among a nationally representative
      sample of working-age adults in the United States. METHODS: We estimate
      multinomial logistic regression models using data from the 2003-2012 American
      Time Use Survey to identify how different types of disabling conditions--net of
      other sociodemographic factors--relate to the likelihood of reporting short (6 h
      or fewer) or long (9 h or more) sleep, versus mid-range (between 6 and 9 h)
      sleep. RESULTS: For respondents with work disabilities versus those without work
      disabilities, the relative risk of short and long sleep is 1.4 and 1.5 times
      (respectively) that of those with mid-range sleep. The risk of short and long
      sleep durations is also higher among respondents with cognitive, physical, or
      multiple impairments. CONCLUSIONS: Individuals with disabilities are less likely
      than those without disabilities to have optimal sleep durations. These results
      demonstrate the importance of health promotion services among this population,
      with specific attention to sleep hygiene interventions.

PMID- 24947575
TI  - Park-based afterschool program to improve cardiovascular health and physical
      fitness in children with disabilities.
AB  - BACKGROUND: Children with disabilities are more likely to be overweight or obese
      and less likely to engage in physical activities versus their peers without
      disabilities. OBJECTIVE: The effect of a structured afterschool program housed in
      a large county parks system on several obesity-related health outcomes among
      children with disabilities was examined. METHODS: Children/adolescents with a
      developmental and/or intellectual disability ages 6-22 (N = 52, mean age 13.7
      years) who participated in an afterschool (either 2010-2011 or 2011-2012 school
      year) health and wellness program called Fit-2-PlayTM were assessed. Pre-post
      comparison of outcome variables (mean height, weight, waist/hip/midarm
      circumference, fitness tests, and a 9-item health and wellness knowledge
      assessment) via general linear mixed models analysis was conducted to evaluate
      the effectiveness of the program for normal and overweight/obese participants.
      RESULTS: Normal weight participants significantly improved pre-post mean number
      of push-ups (9.69-14.23, p = 0.01) and laps on the PACER test (8.54-11.38, p <
      0.01) and the overweight/obese group significantly improved the number of sit ups
      (7.51-9.84, p < 0.01) and push ups (4.77-9.89, p < 0.001). Pre-post mean health
      and wellness knowledge composite scores significantly improved for all
      participants (p < 0.01). CONCLUSIONS: Parks-based afterschool programs can be
      effective community resources for instilling physical health in both normal
      weight and overweight/obese children with disabilities. More studies are needed
      to ascertain whether community-based afterschool health and wellness programs can
      be implemented and sustained across this population.

PMID- 24947576
TI  - Shaping and managing the course of a child's disease: parental experiences with
      osteogenesis imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta (OI), a rare genetic disease, causes
      increased bone fragility. The course of childhood chronic conditions particularly
      rare genetic diseases can be modified by both child and parents. However with
      limited research, shaping and managing that process is not well understood.
      OBJECTIVE: Here we examine how parents of children with severe and mild OI have
      shaped and managed the condition of their child over time. Our goal is to provide
      a in-depth understanding of parental responses to OI. METHODS: This study was
      carried out in a pediatric orthopedic hospital located in Montreal, Canada. Using
      the principles of interpretative description, we conducted semi-structured
      interviews with 48 parents of children diagnosed with OI. RESULTS: We found that
      parental responses to their child' disease are constituted by their feelings and
      their actions. These responses changed over time. We can report four successive
      phases: an initial reaction, acceptance, normalization and passing the baton.
      Each stage affected subsequent stages. Every stage was influenced by the severity
      of OI, parents' individual characteristics, their day-to-day experiences and the
      entourage. CONCLUSION: Our study contributes to increased understanding of
      parental responses to OI and to improved parental responses and ultimately the
      child's coping.

PMID- 24947577
TI  - Conceptual model for quality of life among adults with congenital or early
      deafness.
AB  - BACKGROUND: A conceptual model of health-related quality of life (QoL) is needed
      to describe key themes that impact perceived QoL in adults with congenital or
      early deafness. OBJECTIVE: To revise University of Washington Center for
      Disability Policy and Research's conceptual model of health promotion and QoL,
      with suggestions for applying the model to improving programs or services that
      target deaf adults with early deafness. METHODS: Purposive and theoretical
      sampling of 35 adults who were born or became deaf early was planned in a 1-year
      study. In-depth semi-structured interviews probed deaf adult participants'
      perceptions about quality of life as a deaf individual. Data saturation was
      reached at the 17th interview with 2 additional interviews for validation,
      resulting in a total sample of 19 deaf adults. Coding and thematic analysis were
      conducted to develop the conceptual model. RESULTS: Our conceptual model
      delineates the relationships between health status (self-acceptance, coping with
      limitations), intrinsic (functional communication skills, navigating
      barriers/self-advocacy, resilience) and extrinsic (acceptance by others, access
      to information, educating others) factors in their influence on deaf adult
      quality of life outcomes at home, college, work, and in the community.
      CONCLUSIONS: Findings demonstrate the need for the programs and services to
      consider not only factors intrinsic to the deaf individual but also extrinsic
      factors in enhancing perceived quality of life outcomes among people with a range
      of functional hearing and language preferences, including American Sign Language.

PMID- 24947578
TI  - Is computer-assisted training effective in improving rehabilitative outcomes
      after brain injury? A case-control hospital-based study.
AB  - BACKGROUND: Rehabilitation of impaired cognitive functions begins to be
      considered a standard component of medical care after acquired brain injury.
      Indeed, many evidences support the effectiveness of the two major categories of
      techniques, i.e. the traditional and computer-assisted ones, which are widely
      used in cognitive rehabilitative treatment. OBJECTIVE: Aim of this study is to
      evaluate the effects of pc - cognitive training in brain injury patients.
      METHODS: We studied 35 subjects (randomly divided into two groups), affected by
      traumatic or vascular brain injury, having attended from January 2010 to December
      2012 the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of
      Messina. Cognitive impairment was investigated through psychometric battery,
      administered before (T0) and two months (T1) after the cognitive pc-training,
      which was performed only by the experimental group, in addition to conventional
      treatment. Statistical analysis was performed using Wilcoxon test with a p <
      0.01. RESULTS: At time T0, all patients showed language deficits and cognitive
      alterations in visual attention and memory abilities. After the rehabilitation
      program we noted a global improvement in both the groups. However, at T1, the
      experimental group showed a greater cognitive improvement than the control group,
      with significant differences in nearly all the neuropsychological tests
      performed. CONCLUSIONS: Our data suggest that cognitive pc-training may be a
      promising methodology to optimize the rehabilitation outcomes following brain
      injury.

PMID- 24947579
TI  - Feasibility and usability of experience sampling methodology for capturing
      everyday experiences of individuals with autism spectrum disorders.
AB  - BACKGROUND: Understanding experiences from the perspective of adults with autism
      spectrum disorders (ASD), in the myriad of circumstances in which they find
      themselves every day, is crucial for developing client-centered interventions.
      However, capturing these experiences can be difficult. OBJECTIVE: To investigate
      the feasibility and usability of experience sampling method (ESM), an ecological
      momentary assessment, for studying individuals with ASD. METHODS: Four
      participants (2 males) with Asperger's syndrome or high functioning autism aged
      16-32 years carried an iPod touch or iPhone with a pre-installed ESM survey
      exploring the situation and their perceived internal experiences. Participants
      were asked to respond to the survey 7 times daily, at random times generated by
      the device, for 7 days. RESULTS: A high signal response rate (mean = 71%) and a
      short average time required for survey completion (mean = 1 min 42 s) supported
      feasibility of the ESM for use in research with individuals with ASD.
      Participants reported that the questions were straightforward and that survey
      completion interfered very little with everyday activities, supporting
      acceptability of the method. Results of a split-week analysis revealed
      consistency of experiences; correlations among experiences that are linked
      logically provided evidence of the internal logic of data gathered using the ESM.
      Through graphic analysis, we illustrated the usability of ESM for capturing the
      influence of everyday contexts on internal experiences/perceptions. CONCLUSIONS:
      The ESM holds promise for examining the impact of social context on the everyday
      experiences of individuals with ASD.

PMID- 24947580
TI  - Clinical heterogeneity of abnormal glucose homeostasis associated with the HNF4A
      R311H mutation.

PMID- 24947581
TI  - A novel approach for improving the yield of Bacillus subtilis transglutaminase in
      heterologous strains.
AB  - The transglutaminase (BTG) from Bacillus subtilis is considered to be a new type
      of transglutaminase for the food industry. Given that the BTG gene only encodes a
      mature peptide, the expression of BTG in heterologous microbial hosts could
      affect their normal growth due to BTG's typical transglutaminase activity which
      can catalyze cross-linking of proteins in the cells. Therefore, we developed a
      novel approach to suppress BTG activity and reduce the toxicity on microbial
      hosts, thus improving BTG yield. Genes encoding the respective regions of
      transglutaminase propeptide from seven species of Streptomyces were fused to the
      N-terminal of the BTG gene to produce fusion proteins. We found that all the
      fused propeptides could suppress BTG activity. Importantly, BTG activity could be
      completely restored after the removal of the propeptides by proteolytic cleavage.
      Of the seven propeptides tested, the propeptide proD from Streptomyces caniferus
      had the strongest suppressive effect on BTG activity (70 % of the activity
      suppressed). Moreover, fusion protein proD-BTG (containing proD) also exhibited
      the highest yield which was more than twofold of the expression level of BTG in
      an active form in Escherichia coli. Secretion expression of BTG and proD-BTG in
      Corynebacterium glutamicum further showed that our novel approach was suitable
      for the efficient BTG expression, thus providing a valuable platform for further
      optimization of large-scale BTG production.

PMID- 24947582
TI  - A stress response pathway in mice upregulates somatostatin level and
      transcription in pancreatic delta cells through Gs and beta-arrestin 1.
AB  - AIMS/HYPOTHESIS: Somatostatin secretion from islet delta cells plays an important
      role in regulating islet function and is tightly controlled by environmental
      changes. Activation of the adrenergic system promoted somatostatin secretion from
      islet delta cells; however, the role of the adrenergic system in regulating
      somatostatin content and transcription has not been defined. An imbalance between
      the somatostatin content and its secretion may cause dysfunctions in the islet
      delta cells. We have investigated the role of the adrenergic system in the
      modulation of somatostatin content and transcription in pancreatic delta cells
      and the detailed underlying mechanisms of this regulation. METHODS: The stress
      hormone adrenaline (epinephrine), specific adrenergic agonists or specific
      adrenergic antagonists were applied to islets from either wild-type or specific
      adrenergic receptor knockout mice and pancreatic delta cell lines to investigate
      their effects on somatostatin content and transcription. The GloSensor assay,
      quantitative real-time PCR, western blots and the dual luciferase assay were used
      to monitor the cAMP level, somatostatin expression, activations of kinases and
      transcriptional factors. Arrb1 knockout mice, specific Creb or Pax6 mutations and
      specific kinase inhibitors were used to dissect the signalling pathway. RESULTS:
      Adrenaline and isoprenaline increased somatostatin content and transcription
      through the activation of beta1-/beta2-adrenergic receptors (beta1-/beta2ARs).
      The somatostatin content in beta1AR(-/-) /beta2AR(-/-) (Adrb1/Adrb2 knockout)
      mice was 50% lower than in beta1AR(+/+)/beta2AR (+/+) mice. Two parallel
      signalling pathways, Gs-cAMP-protein kinase A (PKA)-cAMP response element binding
      protein (CREB) and beta-arrestin 1-extracellular signal-related kinase (ERK)
      paired box protein 6 (PAX6), cooperatively regulated isoprenaline-induced
      somatostatin transcription. CONCLUSIONS/INTERPRETATION: A stress pathway
      increased somatostatin content and transcription through beta-adrenergic agonism.
      beta-Arrestin1, ERK and PAX6 are important pancreatic delta cell regulators in
      addition to cAMP, PKA and CREB. Dysfunction of beta-adrenergic agonism may impair
      pancreatic delta cell function.

PMID- 24947584
TI  - Chronic granulomatous disease mimicking early-onset Crohn's disease with
      cutaneous manifestations.
AB  - BACKGROUND: Chronic granulomatous disease is a rare inherited disorder of the
      innate immune system. In patients with a clinical history of recurrent or
      persistent infections, especially infections caused by uncommon species, chronic
      granulomatous disease should be considered. CASE PRESENTATION: We report the case
      of a 5-year-old boy with a presumptive diagnosis of Crohn's disease with
      extraintestinal manifestations. Chronic granulomatous disease was suspected in
      this case after Serratia marcescens was isolated from a skin ulcer culture.
      Granulomas were confirmed on histology and chronic granulomatous disease was
      diagnosed. CONCLUSION: This case emphasizes the importance of high clinical
      suspicion of an alternative diagnosis of immune deficiency in patients with
      presumed inflammatory bowel disease and opportunistic infections, especially when
      disease occurs in early life.

PMID- 24947583
TI  - Liraglutide reverses pronounced insulin-associated weight gain, improves
      glycaemic control and decreases insulin dose in patients with type 2 diabetes: a
      26 week, randomised clinical trial (ELEGANT).
AB  - AIMS/HYPOTHESIS: The best treatment strategy for a patient with type 2 diabetes
      who shows pronounced weight gain after the introduction of insulin treatment is
      unclear. We determined whether addition of a glucagon-like peptide-1 (GLP-1)
      analogue could reverse pronounced insulin-associated weight gain while
      maintaining glycaemic control, and compared this with the most practised
      strategy, continuation and intensification of standard insulin therapy. METHODS:
      In a 26-week, randomised controlled trial (ELEGANT), conducted in the outpatient
      departments of one academic and one large non-academic teaching hospital in the
      Netherlands, adult patients with type 2 diabetes with >= 4% weight gain during
      short-term (<= 16 months) insulin therapy received either open-label addition of
      liraglutide 1.8 mg/day (n = 26) or continued standard therapy (n = 24). A
      computer-generated random number list was used to allocate treatments.
      Participants were evaluated every 4-6 weeks for weight, glycaemic control and
      adverse events. The primary endpoint was between-group weight difference after 26
      weeks of treatment (intention to treat). RESULTS: Of 50 randomised patients (mean
      age 58 years, BMI 33 kg/m(2), HbA1c 7.4% [57 mmol/mol]), 47 (94%) completed the
      study; all patients were analysed. Body weight decreased by 4.5 kg with
      liraglutide and increased by 0.9 kg with standard therapy (mean difference -5.2
      kg [95% CI -6.7, -3.6 kg]; p < 0.001). The respective changes in HbA1c were 
      0.77% (-8.4 mmol/mol) and +0.01% (+0.1 mmol/mol) (difference -0.74% [-8.1
      mmol/mol]) ([95% CI -1.08%, -0.41%] [-11.8, -4.5 mmol/mol]; p < 0.001);
      respective changes in insulin dose were -29 U/day and +5 U/day (difference -33
      U/day [95% CI -41, -25 U/day]; p < 0.001). In five patients (19%), insulin could
      be completely discontinued. Liraglutide was well tolerated; no severe adverse
      events or severe hypoglycaemia occurred. CONCLUSIONS/INTERPRETATION: In patients
      with pronounced insulin-associated weight gain, addition of liraglutide to their
      treatment regimen reverses weight, decreases insulin dose and improves glycaemic
      control, and hence seems a valuable therapeutic option compared with continuation
      of standard insulin treatment. Trial registration ClinicalTrials.gov NCT01392898.
      Funding The study was funded by Novo Nordisk.

PMID- 24947585
TI  - Vitamin D3, D2 and arterial wall properties in coronary artery disease.
AB  - OBJECTIVES: There are two major forms of vitamin D, vitamin D2 (ergocalciferol)
      and vitamin D3 (cholecalciferol). We studied the effect of the different vitamin
      D fractions (D3/D2) on arterial wall properties in coronary artery disease (CAD)
      patients. METHODS: We included 252 subjects with CAD. Endothelial function was
      evaluated by flow mediated dilation (FMD). Carotid femoral pulse wave velocity
      (PWV) was measured as an index of arterial stiffness and augmentation index (AI)
      as a measure of reflected waves. Measures for 25(OH)D2 and 25(OH)D3 were
      performed using Liquid Chromatography Mass Spectrometry technology. RESULTS: From
      the study population, 155(62%), 66(26%) and 31(12%) were categorized as having
      vitamin D deficiency, insufficiency and sufficiency respectively. There was no
      difference between subjects with vitamin D deficiency, insufficiency and
      sufficiency in FMD, AI and PWV (p=NS for all). Subjects with vitamin D
      insufficiency/deficiency had significantly higher D2 to D ratio compared to
      subjects with vitamin D sufficiency. Interestingly, FMD was positively associated
      with D2 to D ratio (rho=0.13, p=0.02) and subjects with D2 levels<0.3ng/ml had
      impaired FMD compared to those with increased D2 levels (p=0.048). CONCLUSION:
      Vitamin D insufficiency/deficiency is highly prevalent in CAD subjects. Vitamin
      D2 concentrations are positively associated with endothelial function. These
      findings may suggest a beneficial role of vitamin D2 levels in vascular health.

PMID- 24947586
TI  - SPARC in Tumor Pathophysiology and as a Potential Therapeutic Target.
AB  - Cell migration and metastasis greatly contribute to the progression of tumors.
      Secreted Protein and Rich in Cysteine (SPARC), as a multi-faceted protein, is
      highly expressed in highly metastatic tumors while low or undetectable in less
      metastatic types with aberrant promoter methylation. In highly metastatic tumors,
      such as glioblastomas, melanoma, breast cancer and prostate cancer, SPARC
      promotes bone metastasis and epithelial-mesenchymal transition (EMT). In
      contrast, this protein acts as an anti-tumor factor in anti-angiogenesis, pro
      apoptosis, cell proliferation inhibition and cell cycle arrest in less metastatic
      tumors, such as neuroblastoma, ovarian cancer, pancreatic cancer, colorectal
      cancer and gastric cancer. Here, we summarize and analyze the paradoxical role of
      SPARC in different tumors. We believe that further studies on truncated,
      alternative splicing variants and signal peptide of SPARC are required to
      elucidate the distinct effects. Most notably, SPARC variants probably play a
      crucial role in regulation of transforming growth factor beta (TGF-beta) induced
      EMT. This review also provides strategies to target or use SPARC (full-length,
      truncated and splicing variants) for therapeutic purposes. 

PMID- 24947587
TI  - Cytomegalovirus infection and postoperative complications in patients with
      ulcerative colitis undergoing colectomy.
AB  - BACKGROUND: Ulcerative colitis (UC) can be complicated by reactivation of
      cytomegalovirus (CMV). CMV reactivation may change the course of UC and may
      require antiviral treatment. Some risk factors of CMV reactivation have
      previously been identified, whereas the association between CMV reactivation and
      postoperative complications has not been examined systematically. METHODS:
      Patients with UC operated with colectomy due to active UC were studied (n = 77).
      Patient and disease characteristics, as well as postoperative complications were
      recorded and CMV was detected by immunohistochemical examination of multiple
      sections from the colectomy specimen. RESULTS: CMV was found in nine (11.7%)
      colectomy specimens. CMV-positive patients received significantly higher doses of
      corticosteroids at colectomy than CMV-negative patients (61.1 +/- 23 vs 32.5 +/-
      32 mg/day, p = 0.01). CMV-positive patients were also older, had a higher risk of
      severe complications, higher American Society of Anesthesiologists (ASA) score,
      longer preoperative stay, and a higher rate of acute surgery. Complications
      occurred in 30 (39%) patients after surgery, 8(10.4%) of whom were serious. Two
      CMV-positive patients (2.6%) died in-hospital after the colectomy. High ASA score
      was associated with the occurrence of serious complications. CONCLUSION: A
      relatively small proportion of patients with UC operated by colectomy were CMV
      positive. CMV positivity was associated with old age, high dose of
      corticosteroids at operation, high ASA score, acute surgery, and severe
      postoperative complications. Patients with such characteristics may be at risk of
      CMV infection and may require special management.

PMID- 24947589
TI  - First recurrent large genomic rearrangement in the BRCA1 gene found in Poland.
AB  - Mutation in the BRCA1 gene increases the risk of the person developing breast
      and/or ovarian cancer. The prevalence and spectrum of large genomic
      rearrangements (LGRs) varies considerably among different tested populations. In
      our previous study we described three LGRs in BRCA1 (exons 13-19, exon 17 and
      exon 22) in Polish families at high risk of breast and ovarian cancer. In this
      study we analyzed a group of 550 unselected women with ovarian cancer for the
      three previously identified LGRs. We used a rapid, single-step and closed-tube
      method: high-resolution melting analysis (HRMA). In this group of unrelated
      patients diagnosed with ovarian cancer we found three cases with the same
      deletions of exon 22. This is the first recurrent large deletion in BRCA1 found
      in Poland. We conclude that screening for the exon 22 deletion in BRCA1 should be
      included in the Polish BRCA1 genetic testing panel and possibly extended into
      other Slavic populations. 

PMID- 24947588
TI  - Longer duration of combination antiretroviral therapy reduces the risk of Hodgkin
      lymphoma: A cohort study of HIV-infected male veterans.
AB  - BACKGROUND: Hodgkin lymphoma (HL) incidence has increased since combined
      antiretroviral therapy (cART) introduction. It is unclear how different cART
      classes (e.g., protease inhibitors (PI), non-nucleoside reverse transcription
      inhibitors (NNRTI)) influence HL. This study aimed to determine the effects of
      cART duration on HL incidence among HIV-infected veterans. METHODS: We performed
      a retrospective cohort study utilizing the Veterans Affairs HIV Clinical Case
      Registry (1985-2010). HL cases were identified using ICD-9 codes (201.4-9). cART,
      PI, and NNRTI duration was the aggregate number of treatment days delivered.
      Incidence rates (IR) and rate ratios (IRR) were calculated from Poisson
      regression models to examine the effects of cART duration on HL. RESULTS: 31,576
      cART users contributed 288,736 person-years (PY) and 211 HL cases (IR=7.3/10,000
      person-years). HL incidence decreased from 25.1/10,000 PY (95%CI=18.9-33.4)
      within the first year of cART to 0.6/10,000 PY (95%CI=0.3-1.6) after >= 10 years.
      In multivariable models, each additional year of cART was associated with
      decreased HL incidence (IRR=0.80; 95%CI=0.75-0.86); similar effects were observed
      in models assessing HL incidence by PI and NNRTI. CONCLUSION: Our findings
      indicate long-term cART of any class is associated with decreased HL risk. High
      HL incidence directly following cART initiation supports a potential immune
      reconstitution mechanism in HIV-related HL. Further research is needed to
      evaluate the interaction between early cART, immune reconstitution, and HL.

PMID- 24947590
TI  - Recovery after anaesthesia and surgery.

PMID- 24947593
TI  - Tracking EEG changes during the exposure to hyperbaric oxygen.
AB  - OBJECTIVE: The aim was to investigate and define possible alterations in cerebral
      activity during prolonged hyperbaric oxygen exposure and decompression as
      compared to baseline activity. METHODS: Thirty-two channel electroencephalography
      (EEG) was recorded with a Bluetooth EEG system in 11 subjects. A 20-min EEG
      recording was carried out under three different conditions: breathing air inside
      a hyperbaric chamber at sea level; breathing oxygen at a simulated depth of 18
      msw; breathing air at sea level after decompression. Relative EEG power was
      estimated in frequency ranges. RESULTS: During oxygen breathing, brain activity
      showed an early fast delta decrease in the posterior regions, with a synchronous
      and significant increase in alpha in the same regions. After decompression, the
      delta relative power decrease was uniformly distributed over the cerebral cortex
      until minute 8, and the alpha relative power was maximal in the posterior regions
      during the first 2 min. CONCLUSIONS: These results may be relevant for
      establishing a reference point in future studies on oxygen-sensitive subjects who
      reported problems during oxygen diving. SIGNIFICANCE: Significant changes in EEG
      relative power suggest that it may be possible to define and recognize landmarks
      of oxygen-induced brain activity, which would be useful in the medical treatment
      of subjects reporting "oxygen-toxicity diving-related problems".

PMID- 24947594
TI  - Neurophysiological correlates of sleep leg movements in acute spinal cord injury.
AB  - OBJECTIVE: The objective of this study was to analyze the periodicity of leg
      movement activity emerging during sleep in a group of patients with spinal cord
      injury and to evaluate their pathophysiological features. METHODS: Twenty
      patients (16 males, mean age 34.0 years) with traumatic spinal cord lesions were
      recruited (5 cervical, 15 thoracic; 16 level A and 4 level B at the American
      Spinal Injury Association impairment scale). Periodicity of sleep leg movements
      was analyzed; electroencephalographic spectral analysis and heart rate were
      evaluated for 20s preceding and 30s following the onset of leg movements.
      RESULTS: Periodic leg movements during sleep (PLMS) index >5/h was found in only
      4 patients and only 2 of these had PLMS index >15/h. Eleven patients (group I)
      did not show any increase in heart rate related to the occurrence of leg
      movements while the remaining 9 did (group II). Two patients in each group had
      American Spinal Injury Association impairment level B; 5 patients of group I and
      none of group II had cervical lesions while 6 patients of group I and all 9 of
      group II had thoracic lesions. Only 2 patients in group I presented clearly
      periodic leg movements during sleep and PLMS index >15/h. Electroencephalographic
      delta, alpha and beta bands around leg movements increased clearly in group II
      while the changes in group I were very limited or absent. CONCLUSION: Leg
      movements during sleep are recorded in spinal cord injury patients with
      completely absent volitional activity in their lower limb but they show clear
      periodicity only in a small subgroup of them. SIGNIFICANCE: The disconnection
      from higher nervous structures, in patients with spinal cord injury might favor
      the appearance of leg movements due to the activity of spinal generators not
      inhibited by higher influences; correlated autonomic and electroencephalographic
      changes can be absent. This motor activity might assume the periodic character
      when a genetic predisposition is present.

PMID- 24947595
TI  - Cumulative effects of transcranial direct current stimulation on EEG oscillations
      and attention/working memory during subacute neurorehabilitation of traumatic
      brain injury.
AB  - OBJECTIVE: To investigate in a randomized, double-blind design, cumulative
      effects of anodal tDCS on EEG oscillations and neuropsychological tests among
      patients with traumatic brain injury (TBI) undergoing subacute
      neurorehabilitation. METHODS: Twenty-six patients were randomly assigned to
      active (n=13) or sham (n=13) tDCS groups. EEGs were recorded at 6 different time
      points, assessing both immediate and cumulative effects of tDCS on EEG
      oscillations. Twenty minute sessions of 1mA anodal stimulation to the left
      dorsolateral prefrontal cortex (F3, cathode placed at right supraorbital site,
      Fp2), were provided on 10 consecutive days. Neuropsychological tests were
      administered before and after the series of tDCS sessions. RESULTS: Theta was
      significantly reduced for active tDCS patients following the first tDCS session.
      Delta decreased and alpha increased, both significantly, for the active tDCS
      group after 10 consecutive tDCS sessions. No significant changes were seen for
      sham group. Decreases in delta were significantly correlated with improved
      performance on neuropsychological tests for the active tDCS group to far greater
      degree than for the sham group. Participants in the active tDCS group who had
      excess slow EEG activity in their initial recordings showed greater improvement
      on neuropsychological tests than other groups. CONCLUSION: Results suggest that
      10 anodal tDCS sessions may beneficially modulate regulation of cortical
      excitability for patients with TBI. SIGNIFICANCE: EEG-guided tDCS warrants
      further investigation as a potential intervention for TBI during subacute
      neurorehabilitation.

PMID- 24947597
TI  - Contraceptive options for women living with HIV.
AB  - Women living with HIV are often of reproductive age, and many desire effective
      contraceptive options to delay or prevent pregnancy. We review the safety of
      various hormonal and non-hormonal contraceptive methods for women living with
      human immunodeficiency virus (HIV). Additionally, we discuss drug interactions
      between contraceptive methods and antiretrovirals and the safety of methods with
      respect to onward transmission to HIV-negative partners for women in sero
      discordant partnerships. In general, most methods are safe for most women living
      with HIV. An understanding of the reproductive goals of each individual patient,
      as well as her medical condition and medication, should be taken into account
      when counselling women on their contraceptive options. Further research is needed
      to understand drug interactions between contraceptives and antiretrovirals better
      and how to fulfil the contraceptive needs of HIV-positive women. 

PMID- 24947596
TI  - Bikinin-like inhibitors targeting GSK3/Shaggy-like kinases: characterisation of
      novel compounds and elucidation of their catabolism in planta.
AB  - BACKGROUND: Plant GSK-3/Shaggy-like kinases are key players in brassinosteroid
      (BR) signalling which impact on plant development and participate in response to
      wounding, pathogens and salt stress. Bikinin was previously identified in a
      chemical genetics screen as an inhibitor targeting these kinases. To dissect the
      structural elements crucial for inhibition of GSK-3/Shaggy-like kinases by
      bikinin and to isolate more potent compounds we synthesised a number of related
      substances and tested their inhibitory activity in vitro and in vivo using
      Arabidopsis thaliana. RESULTS: A pyridine ring with an amido succinic acid
      residue in position 2 and a halogen in position 5 were crucial for inhibitory
      activity. The compound with an iodine substituent in position 5, denoted
      iodobikinin, was most active in inhibiting BIN2 activity in vitro and efficiently
      induced brassinosteroid-like responses in vivo. Its methyl ester,
      methyliodobikinin, showed improved cell permeability, making it highly potent in
      vivo although it had lower activity in vitro. HPLC analysis revealed that the
      methyl residue was rapidly cleaved off in planta liberating active iodobikinin.
      In addition, we provide evidence that iodobikinin and bikinin are inactivated in
      planta by conjugation with glutamic acid or malic acid and that the latter
      process is catalysed by the malate transferase SNG1. CONCLUSION: Brassinosteroids
      participate in regulation of many aspects of plant development and in responses
      to environmental cues. Thus compounds modulating their action are valuable tools
      to study such processes and may be an interesting opportunity to modify plant
      growth and performance in horticulture and agronomy. Here we report the
      development of bikinin derivatives with increased potency that can activate BR
      signalling and mimic BR action. Methyliodobikinin was 3.4 times more active in
      vivo than bikinin. The main reason for the superior activity of
      methyliodobikinin, the most potent compound, is its enhanced plant tissue
      permeability. Inactivation of bikinin and its derivatives in planta involves
      SNG1, which constitutes a novel pathway for modification of xenobiotic compounds.

PMID- 24947598
TI  - Contraceptive needs of the adolescent.
AB  - The provision of contraception to adolescents requires specific attention.
      Adolescents require contraceptive methods which are safe, effective and simple to
      use. While long-acting reversible contraceptive methods are preferable, they
      should have a choice and not be forced or mandated especially in situations where
      this may compromise safety. After counselling they should have the ability to
      choose any method of contraception. Under the appropriate circumstances, each
      method of contraception may have a place. This chapter will be devoted to
      evaluating the most current scientific rationale for the indication for use of
      each method of contraception in adolescents. 

PMID- 24947600
TI  - The intrauterine device and the intrauterine system.
AB  - Intrauterine contraception is used by about 100 million women worldwide, making
      it the most popular form of fertility regulation. In UK community contraception
      clinics, however, long-acting reversible contraception has increased to 28% of
      users, and intrauterine contraception accounts for only 8% of methods used by
      women accessing these services. Potential exists to increase uptake of these more
      effective methods. In this chapter, we review the clinical advantages,
      disadvantages and cost-effectiveness of intrauterine contraception. We discuss
      the management of complications along with advice for trainers, and briefly
      consider issues in developing countries. 

PMID- 24947599
TI  - Male contraception.
AB  - Clear evidence shows that many men and women would welcome new male methods of
      contraception, but none have become available. The hormonal approach is based on
      suppression of gonadotropins and thus of testicular function and spermatogenesis,
      and has been investigated for several decades. This approach can achieve
      sufficient suppression of spermatogenesis for effective contraception in most
      men, but not all; the basis for these men responding insufficiently is unclear.
      Alternatively, the non-hormonal approach is based on identifying specific
      processes in sperm development, maturation and function. A range of targets has
      been identified in animal models, and targeted effectively. This approach,
      however, remains in the pre-clinical domain at present. There are, therefore,
      grounds for considering that safe, effective and reversible methods of
      contraception for men can be developed. 

PMID- 24947602
TI  - A four-year survey on unexpected pregnancy diagnoses in a large urban emergency
      department in Parma, Italy.
AB  - OBJECTIVE: To investigate the rate of unexpected pregnancy diagnoses in the
      emergency department of the Academic Hospital of Parma, Parma, Italy. METHODS:
      Data for all patients with a positive beta-human chorionic gonadotropin test
      between October 2008 and September 2012 were retrieved from the hospital records.
      Information on age, gender, country of birth, and reason for presenting to the
      emergency department was collected. RESULTS: During the study period, 160151
      visits of female patients were recorded, including 385 (0.2%) women who received
      a diagnosis of pregnancy; 97 (25.2%) were native Italians and 288 (74.8%) were
      foreign-born. The percentage of women presenting for trauma did not differ
      between the two groups, whereas the rate of admission to the obstetrics and
      gynecology department was higher among natives (20.6% vs 9.0%; P=0.002). Africans
      represented 66.0% (n=190) of the women with an unexpected pregnancy diagnosis.
      Nigerians accounted for 20.8% (n=60) of all foreign-born women with a pregnancy
      diagnosis, although they represented less than 2% of the entire immigrant
      population. CONCLUSION: Unexpected pregnancy is a problem in the province of
      Parma, most notably among women from Sub-Saharan Africa. Efforts should be
      strengthened to provide more fragile groups with easily available family planning
      information.

PMID- 24947601
TI  - Compromised maturation of GABAergic inhibition underlies abnormal network
      activity in the hippocampus of epileptic Ca2+ channel mutant mice, tottering.
AB  - Cholinergically induced network activity is a useful analogue of theta rhythms
      involved in memory processing or epileptiform activity in the hippocampus,
      providing a powerful tool to elucidate the mechanisms of synchrony in neuronal
      networks. In absence epilepsy, although its association with cognitive
      impairments has been reported, the mechanisms underlying hippocampal synchrony
      remain poorly investigated. Here we simultaneously recorded electrical activities
      from 64 sites in hippocampal slices of CaV2.1 Ca(2+) channel mutant tottering
      (tg) mice, a well-established mouse model of spontaneous absence epilepsy, to
      analyze the spatiotemporal pattern of cholinergically induced hippocampal network
      activity. The cholinergic agonist carbachol induced oscillatory discharges
      originating from the CA3 region. In tg/tg mice, this hippocampal network activity
      was characterized by enhanced occupancy of discharges of relatively high
      frequency (6-10 Hz) compared to the wild type. Pharmacological analyses of
      slices, patch clamp electrophysiological characterization of isolated neurons,
      and altered patterns of hippocampal GABAA receptor subunit and Cl(-) transporter
      messenger RNA (mRNA) transcript levels revealed that this abnormality is
      attributable to a developmental retardation of GABAergic inhibition caused by
      immature intracellular Cl(-) regulation. These results suggest that the inherited
      CaV2.1 Ca(2+) channel mutation leads to developmental abnormalities in Cl(-)
      transporter expression and GABAA receptor compositions in hippocampal neurons and
      that compromised maturation of GABAergic inhibition contributes to the abnormal
      synchrony in the hippocampus of tg absence epileptic mice.

PMID- 24947603
TI  - Reproducibility of cervical intraepithelial neoplasia diagnosis on histological
      review of cervical punch biopsies from a visual inspection with acetic acid and
      HPV detection-based screening program.
AB  - OBJECTIVE: To assess the reproducibility of cervical intraepithelial neoplasia
      (CIN) diagnosis in a visual inspection with acetic acid (VIA) and HPV detection
      based screening program, and to correlate CIN diagnosis with oncogenic HPV
      status. METHODS: A total of 9630 women were screened by VIA and high-risk HPV
      detection at community outreach clinics in India between June 2011 and June 2012.
      Biopsies obtained from women who were positive on either test were reviewed by
      two pathologists blinded to the histological diagnoses originally made by
      pathologists working at the Chittaranjan National Cancer Institute. RESULTS: The
      interobserver agreement between the pathologists' diagnoses and the diagnoses
      made by the expert reviewers on 424 slides was fair (kappa = 0.26). There was a
      distinct difference in agreement in detecting CIN 2 (kappa = 0.21) and detecting
      CIN 3 (kappa = 0.74). The overall agreement in diagnosis improved when the slides
      obtained from the HPV-positive women were considered (kappa = 0.5). Almost half
      of the discordant CIN 2 cases were high-risk HPV negative. CONCLUSION: Diagnosis
      of CIN 2 is poorly reproducible. The natural history of CIN 2 lesions is more
      similar to CIN 1 than CIN 3; it is therefore necessary to re-evaluate whether to
      consider CIN 2 lesions as high-grade squamous intraepithelial lesions with CIN 3,
      as in the Bethesda system of classification.

PMID- 24947604
TI  - The relationship between female genital cutting and women's autonomy in Eritrea.
AB  - OBJECTIVE: To investigate the relationship between women's autonomy and attitudes
      toward female genital cutting (FGC) and having a daughter with FGC in Eritrea.
      METHODS: Data from a nationally representative sample of 8754 women aged between
      15 and 49 years from the 2002 Eritrea Demographic and Health Survey were
      analyzed. Multivariate logistic regression was used to determine significant
      predictors of the practice of and attitudes toward FGC, including women's
      autonomy. RESULTS: Sixty-three percent (n = 3168) of women sampled had at least
      one daughter who had undergone FGC and 50.1% (n = 4848) of women believed FGC
      should continue. When controlling for sociodemographic characteristics, the odds
      of supporting the continuation of FGC were greater among women who justified wife
      beating (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.23-1.66).
      Among women who participated in household decisions, the odds of them supporting
      the continuation of FGC were less than among women who did not participate in
      household decisions (aOR 0.87; 95% CI, 0.75-0.99). CONCLUSION: Interventions
      addressing women's autonomy, specifically attitudes toward gender norms and
      increasing women's involvement in household decisions that carry a greater
      responsibility, may be a useful approach to reduce the support for and practice
      of FGC.

PMID- 24947605
TI  - PIRIN2 stabilizes cysteine protease XCP2 and increases susceptibility to the
      vascular pathogen Ralstonia solanacearum in Arabidopsis.
AB  - PIRIN (PRN) is a member of the functionally diverse cupin protein superfamily.
      There are four members of the Arabidopsis thaliana PRN family, but the roles of
      these proteins are largely unknown. Here we describe a function of the
      Arabidopsis PIRIN2 (PRN2) that is related to susceptibility to the bacterial
      plant pathogen Ralstonia solanacearum. Two prn2 mutant alleles displayed
      decreased disease development and bacterial growth in response to R. 
      solanacearum infection. We elucidated the underlying molecular mechanism by
      analyzing PRN2 interactions with the papain-like cysteine proteases (PLCPs) XCP2,
      RD21A, and RD21B, all of which bound to PRN2 in yeast two-hybrid assays and in
      Arabidopsis protoplast co-immunoprecipitation assays. We show that XCP2 is
      stabilized by PRN2 through inhibition of its autolysis on the basis of PLCP
      activity profiling assays and enzymatic assays with recombinant protein. The
      stabilization of XCP2 by PRN2 was also confirmed in planta. Like prn2 mutants, an
      xcp2 single knockout mutant and xcp2 prn2 double knockout mutant displayed
      decreased susceptibility to R. solanacearum, suggesting that stabilization of
      XCP2 by PRN2 underlies susceptibility to R. solanacearum in Arabidopsis. 

PMID- 24947606
TI  - Adoptive immunotherapy with MUC1-mRNA transfected dendritic cells and cytotoxic
      lymphocytes plus gemcitabine for unresectable pancreatic cancer.
AB  - BACKGROUND: We previously reported the clinical efficacy of adoptive
      immunotherapy (AIT) with dendritic cells (DCs) pulsed with mucin 1 (MUC1) peptide
      and cytotoxic T lymphocytes (CTLs). We also reported that gemcitabine (GEM)
      enhances anti-tumor immunity by suppressing regulatory T cells. Therefore, in the
      present study, we performed combination therapy with AIT and GEM for patients
      with unresectable or recurrent pancreatic cancer. PATIENTS AND METHODS: Forty-two
      patients with unresectable or recurrent pancreatic cancer were treated. DCs were
      generated by culture with granulocyte macrophage colony-stimulating factor and
      interleukin-4 and then exposed to tumor necrosis factor-alpha. Mature DCs were
      transfected with MUC1-mRNA by electroporation (MUC1-DCs). MUC1-CTLs were induced
      by co-culture with YPK-1, a human pancreatic cancer cell line, and then with
      interleukin-2. Patients were treated with GEM, while MUC1-DCs were intradermally
      injected, and MUC1-CTLs were intravenously administered. RESULTS: Median survival
      time (MST) was 13.9 months, and the 1-year survival rate was 51.1%. Of 42
      patients, one patient had complete response (2.4%), three patients had partial
      response (7.1%) and 22 patients had stable disease (52.4%). The disease control
      ratio was 61.9%. The MST and 1-year survival rate of 35 patients who received
      more than 1 * 10(7) MUC1-DCs per injection was 16.1 months and 60.3%,
      respectively. Liver metastasis occurred in only 5 patients among 35 patients
      without liver metastasis before treatment. There were no severe toxicities
      associated with AIT. CONCLUSION: AIT with MUC1-DCs and MUC1-CTLs plus GEM may be
      a feasible and effective treatment for pancreatic cancer.

PMID- 24947608
TI  - Solution structures and model membrane interactions of Ctriporin, an anti
      methicillin-resistant Staphylococcus aureus Peptide from Scorpion Venom.
AB  - Ctriporin peptide (Ctr), a novel antimicrobial peptide isolated from the venom of
      the scorpion Chaerilus tricostatus, shows a broad-spectrum of antimicrobial
      activity and is able to inhibit antibiotic resistant pathogens, including
      Methicillin resistant Staphylococcus aureus, Methicillin Resistant Coagulase
      negative Staphylococcus, and Penicillin Resistant Staphylococcus epidermidis
      strains. To understand the active conformation of the Ctr peptide in membranes,
      we have investigated the interaction of Ctr with the negatively charged and
      zwitterionic membrane-mimetic micelles such as sodium dodecyl sulphate (SDS) and
      n-dodecylphosphocholine (DPC), respectively. The interactions were studied using
      fluorescence and circular dichroism (CD) spectroscopy. Fluorescence experiments
      revealed that the N-terminus tryptophan residue of Ctr interacted with the
      hydrophobic core of the membrane mimicking micelles. The CD results suggest that
      interactions with membrane-mimetic micelles induce an alpha-helix conformation in
      Ctr. Moreover, we have determined the solution structures of Ctr in SDS and DPC
      micelles using nuclear magnetic resonance (NMR) spectroscopy. The structural
      comparison of Ctr in the presence of SDS and DPC micelles showed significant
      conformational changes. The observed structural differences of Ctr in anionic
      versus zwitterionic membrane-mimetic micelles suggest that the mode of
      interaction of this peptide may be different in two environments which may
      account for its ability to differentiate bacterial and eukaryotic cell membrane.

PMID- 24947607
TI  - clpC operon regulates cell architecture and sporulation in Bacillus anthracis.
AB  - The clpC operon is known to regulate several processes such as genetic
      competence, protein degradation and stress survival in bacteria. Here, we
      describe the role of clpC operon in Bacillus anthracis. We generated knockout
      strains of the clpC operon genes to investigate the impact of CtsR, McsA, McsB
      and ClpC deletion on essential processes of B. anthracis. We observed that
      growth, cell division, sporulation and germination were severely affected in mcsB
      and clpC deleted strains, while none of deletions affected toxin secretion.
      Growth defect in these strains was pronounced at elevated temperature. The growth
      pattern gets restored on complementation of mcsB and clpC in respective mutants.
      Electron microscopic examination revealed that mcsB and clpC deletion also causes
      defect in septum formation leading to cell elongation. These vegetative cell
      deformities were accompanied by inability of mutant strains to generate
      morphologically intact spores. Higher levels of polyhydroxybutyrate granules
      accumulation were also observed in these deletion strains, indicating a defect in
      sporulation process. Our results demonstrate, for the first time, the vital role
      played by McsB and ClpC in physiology of B. anthracis and open up further
      interest on this operon, which might be of importance to success of B. anthracis
      as pathogen.

PMID- 24947610
TI  - Laser-enhanced cytotoxicity of zoledronic acid and cisplatin on primary human
      fibroblasts and head and neck squamous cell carcinoma cell line UM-SCC-3.
AB  - INTRODUCTION: Low-level laser therapy (LLLT) is used in parodontitis treatment in
      combination with an antimicrobial photosensitizer. The purpose of this study was
      to investigate the combination of LLLT with cisplatin and zoledronic acid as
      potential photosensitizer in-vitro. MATERIALS AND METHODS: Primary human
      fibroblasts (PHF) and head and neck squamous cell carcinoma cells (HNSCC, exactly
      UM-SCC-3) were treated with different concentrations of zoledronatic acid and
      cisplatin and irradiated twice with a diode laser (wavelength 670 nm, 2 min).
      Cell viability was tested by XTT assay and histomorphological analysis with HE
      staining. RESULTS: LLLT increased bioviability for both cell lines (p < 0.001).
      LLLT lowered PHF viability at the highest concentrations of cisplatin (p = 0.027
      and p = 0.005) and zoledronic acid (p < 0.001). For HNSCCs, LLLT reduced cell
      viability at every concentration of cisplatin (all p < 0.05). In cases of
      incubation with zoledronic acid, similar to fibroblasts, laser therapy lowered
      cell viability at the highest concentration only (p < 0.001). CONCLUSIONS: Within
      the limits of this study, it can be concluded that LLLT enhances the effect of
      cisplatin and zoledronic acid in the discussed cells in order to develop new
      therapeutic options for cysts in the cranio-maxillofacial region and other
      appropriate indications.

PMID- 24947611
TI  - Long term surgical outcomes of orbital cavernous haemangiomas (low-flow venous
      malformations) as performed in a tertiary eye hospital in China.
AB  - OBJECTIVE: To assess the long term efficacy and safety of surgical management of
      orbital cavernous haemangiomas (OCH) as performed in a tertiary eye hospital in
      China. METHODS: A retrospective study with 74 OCH patients treated in the Eye
      Hospital, at the Zhongshan Ophthalmic Center, of Sun Yat-Sen University was
      performed covering a period from January 2002 to April 2010. The surgical
      approach, treatment results and visual outcome were recorded and analysed.
      RESULTS: Surgery was performed in all 74 patients and all tumours were completely
      removed. Among them, 93% of the cases (69/74) underwent anterior orbitotomy, with
      43% (30/69) by a cutaneous approach, 57% (39/69) by a conjunctival approach and
      only 7% of the cases (5/74) used a lateral orbitotomy. The mean follow-up time
      was 4.6 years (range 2.0 to 10.0 years). Visual acuity improved in 32.4% of cases
      and deteriorated in 8.2% of cases. No residual proptosis existed. A complicated
      permanent pupil change was present in three cases and only one case showed a
      permanent slight motility deficit. Two cases with multiple masses recurred at two
      years after the first surgery, but neither recurring as assessed at 2 and 5 years
      after the second surgery. CONCLUSIONS: Most OCHs can be removed by anterior
      orbitotomy, using either a cutaneous or conjunctival approach. Anterior
      orbitotomy is a safe, convenient and effective surgical approach for OCH.

PMID- 24947609
TI  - Identification of multiple small heat-shock protein genes in Plutella xylostella
      (L.) and their expression profiles in response to abiotic stresses.
AB  - We identify and characterize 14 small heat-shock protein (sHSP) genes from the
      diamondback moth (DBM), Plutella xylostella (L.), a destructive pest.
      Phylogenetic analyses indicate that, except for sHSP18.8 and sHSP19.22, the other
      12 DBM sHSPs belong to five known insect sHSP groups. Developmental expression
      analysis revealed that most sHSPs peaked in the pupal and adult stages. The
      transcripts of sHSPs display tissue specificity with two exhibiting constitutive
      expression in four tested tissues. Expression of sHSP18.8 in fourth instar larvae
      is not induced by the tested abiotic stressors, and unless sHSP21.8 is not
      sensitive to thermal stress, 12 sHSPs are significantly up-regulated. The
      messenger RNA (mRNA) levels of all sHSPs are reduced under oxidative stress. Food
      deprivation leads to significant down-regulation of three sHSPs. The majority of
      sHSPs show expression variation to various heavy metals, whereas mRNA abundances
      of sHSP22.1 and sHSP 28.9 are reduced by four heavy metals. The responses of
      sHSPs to indoxacarb and cantharidin are varied. Beta-cypermethrin and
      chlorfenapyr exposure results in an increase of 13 sHSP transcripts and a
      reduction of 12 sHSP transcripts, respectively. These results show that different
      sHSPs might play distinct roles in the development and regulation of
      physiological activities, as well as in response to various abiotic stresses of
      DBM. 

PMID- 24947612
TI  - The prevalence of human papilloma virus (HPV) infections in oral squamous cell
      carcinomas: a retrospective analysis of 88 patients and literature overview.
AB  - In addition to tobacco and alcohol consumption, the two main risk factors for
      oral squamous cell carcinoma (OSCC), recent studies have revealed infections with
      human papilloma virus (HPV) as an additional risk factor for OSCC development. In
      the field of head and neck malignancies, the prevalence of HPV infections in
      oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV
      infection is discussed as an independent risk factor in this region, its
      distinguished role in carcinogenesis of tumours localized to the oral cavity
      remains still uncertain. In this study, we analysed the HPV status in 88
      consecutive patients with OSCCs localized anterior of the palatoglossal arch who
      were treated in the Department of Oral and Maxillofacial Surgery at the
      University Medical Center Mainz. The HPV status analysis was performed using DNA
      PCR and immunostaining of p16 protein. The prevalence of HPV-positive OSCCs was
      about 6% (5 patients). In 3 patients the HPV subtypes 16/18 were found. No
      significant differences between the HPV positive and negative patients regarding
      age, gender, smoking and alcohol consumption, localization and TNM level could be
      detected. Contrary to other studies focussing on cancers of the lingual and
      palatine tonsil, the prevalence of HPV infections was much lower in the oral
      cavity. Therefore HPV infection might play a less important role in oral
      carcinogenesis. 

PMID- 24947613
TI  - Interactions between differential fatty acids and inflammatory stressors-impact
      on metabolic health.
AB  - Current interest in obesity has established a clear link between diets high in
      fat and metabolic complications such as Type 2 Diabetes. Dietary fats and their
      metabolites act as stressors to induce a pro-inflammatory immune response which
      dysregulates many essential metabolic functions. Recent research suggests that
      different dietary fats may have varying inflammatory potentials. However the
      molecular mechanisms involved in the cross talk between dietary fat composition
      and the 'immuno-metabolism' remain enigmatic. It is probable that lipids, and
      their derivatives, differentially regulate IL-1beta activation and inflammatory
      signaling via the NLRP3 inflammasome complex. Also from the translational
      perspective, certain nutrient sensitive genotypes and potential gene nutrient
      interactions offer the possibility to reduce inflammation through personalized
      nutrition approaches. 

PMID- 24947614
TI  - Development of online diary and self-management system on e-Healthcare for
      asthmatic children in Taiwan.
AB  - OBJECTIVE: Many regional programs of the countries educate asthmatic children and
      their families to manage healthcare data. This study aims to establish a Web
      based self-management system, eAsthmaCare, to promote the electronic healthcare
      (e-Healthcare) services for the asthmatic children in Taiwan. The platform can
      perform real time online functionality based upon a five-tier infrastructure with
      mutually supportive components to acquire asthma diaries, quality of life
      assessments and health educations. METHODS: We have designed five multi
      disciplinary portions on the interactive interface functioned with the analytical
      diagrams: (1) online asthma diary, (2) remote asthma assessment, (3)
      instantaneous asthma alert, (4) diagrammatical clinic support, and (5) asthma
      health education. The Internet-based asthma diary and assessment program was
      developed for patients to process self-management healthcare at home. In
      addition, the online analytical charts can help healthcare professionals to
      evaluate multi-domain health information of patients immediately. RESULTS:
      eAsthmaCare was developed by JavaTM Servlet/JSP technology upon Apache TomcatTM
      web server and OracleTM database. Forty-one voluntary asthmatic children (and
      their parents) were intervened to examine the proposed system. Seven domains of
      satisfiability assessment by using the system were applied for approving the
      development. The average scores were scaled in the acceptable range for each
      domain to ensure feasibility of the proposed system. CONCLUSION: The study
      revealed the details of system infrastructure and developed functions that can
      help asthmatic children in self-management for healthcare to enhance
      communications between patients and hospital professionals.

PMID- 24947615
TI  - Hepatoprotective role of Sestrin2 against chronic ER stress.
AB  - Upon prolonged endoplasmic reticulum (ER) stress, cells attenuate protein
      translation to prevent accumulation of unfolded proteins. Here we show that
      Sestrin2 is critical for this process. Sestrin2 expression is induced by an ER
      stress-activated transcription factor CCAAT-enhancer-binding protein beta
      (c/EBPbeta). Once induced, Sestrin2 halts protein synthesis by inhibiting
      mammalian target of rapamycin complex 1 (mTORC1). As Sestrin2-deficient cells
      continue to translate a large amount of proteins during ER stress, they are
      highly susceptible to ER stress-associated cell death. Accordingly, dietary or
      genetically induced obesity, which does not lead to any pathological indication
      other than simple fat accumulation in the liver of wild-type (WT) mice, can
      provoke Sestrin2-deficient mice to develop severe ER stress-associated liver
      pathologies such as extensive liver damage, steatohepatitis and fibrosis. These
      pathologies are suppressed by liver-specific Sestrin2 reconstitution, mTORC1
      inhibition or chemical chaperone administration. The Sestrin2-mediated unfolded
      protein response (UPR) may be a general protective mechanism against ER stress
      associated diseases. 

PMID- 24947617
TI  - Reduced Kruppel-like factor 17 (KLF17) expression correlates with poor survival
      in patients with gastric cancer.
AB  - BACKGROUND AND AIMS: To investigate the expression and prognostic significance of
      Kruppel-like factor 17 (KLF17) in human gastric cancer. METHODS: KLF17
      expressions in 158 paraffin-embedded gastric cancer samples were analyzed using
      immunohistochemistry. In addition, KLF17 expressions patterns in three fresh
      gastric cancer tissues and noncancerous gastric mucosa were examined by Western
      blotting. The correlation between KLF17 expression and clinicopathological
      factors as well as patient survival was investigated. RESULTS:
      Immunohistochemical staining data indicated that KLF17 expression was
      significantly decreased in 98 of 158 gastric adenocarcinoma cases. Reduced KLF17
      expression in fresh gastric cancer tissues was confirmed by Western blotting.
      Reduced expression of KLF17 was strongly correlated with tumor size, pN stage and
      lymphovascular invasion. Multivariate Cox regression analysis identified KLF17
      expression as an independent prognostic factor for both overall survival (HR =
      0.481, 95% CI = 0.225-0.665, p = 0.009) and disease-free survival (HR = 0.438,
      95% CI = 0.254-0.758, p = 0.003). CONCLUSION: The reduced expression of KLF17
      protein in gastric cancer was correlated with tumor size, pN stage and
      lymphovascular invasion and was an independent predictor for poor survival in
      patients undergoing surgery for gastric cancer.

PMID- 24947618
TI  - Major congenital anomalies in a Danish region.
AB  - INTRODUCTION: This study describes the prevalence of congenital anomalies and
      changes over time in birth outcome, mortality and chronic maternal diseases.
      MATERIAL AND METHODS: This study was based on population data from the EUROCAT
      registry covering the Funen County, Denmark, 1995-2008. The registry covers live
      births, foetal deaths with a gestational age (GA) of 20 weeks or more, and
      terminations of pregnancy due to congenital anomalies (TOPFA). RESULTS: The
      overall prevalence of congenital anomalies was 2.70% (95% confidence interval:
      2.58-2.80). The majority of cases had an isolated congenital anomaly, 13.9% had a
      chromosomal anomaly and 7.7% were multiple congenital anomalies. The combined
      foetal and infant mortality in the study area was 11.6 per 1,000 births. 19% (2.2
      per 1,000) of these deaths were foetuses and infants with major congenital
      anomalies. Combined foetal and infant mortality decreased significantly over time
      for cases with major congenital anomalies (p < 0.001), whereas the number and
      proportion of TOPFA increased. Median GA at TOPFA decreased from 18 to 15 weeks.
      Among the congenital anomaly cases, 8% had a registration of one of these chronic
      maternal diseases: diabetes, epilepsy, mental disorder, thyroid disease, asthma,
      or inflammatory bowel disease. Medication for these conditions accounted for 46%
      of maternal drug use. CONCLUSION: Maternal morbidity and use of potentially
      teratogenic medication have increased among congenital anomaly cases. Foetal and
      infant mortality for congenital anomaly cases have decreased significantly,
      probably owing to an increase in early prenatal diagnosis and TOPFA. FUNDING: The
      study was funded by Region of South Denmark. TRIAL REGISTRATION: not relevant.

PMID- 24947616
TI  - Tumor suppressor FOXO3 regulates ribonucleotide reductase subunit RRM2B and
      impacts on survival of cancer patients.
AB  - The role of Ribonucleotide reductase (RR) subunits in different cancers has been
      intensively studied in our laboratory. RRM2B was identified as a p53-inducible RR
      subunit that involves in various critical cellular mechanisms such as cell cycle
      regulation, DNA repair and replication, and mitochondrial homeostasis, etc.
      However, little is known about the p53-independent regulation of RRM2B in cancer
      pathology. In this study, we discovered tumor suppressor FOXO3 as the novel
      regulator of RRM2B. FOXO3 directly bound to and transcriptionally activated the
      promoter of RRM2B, and induced the expression of RRM2B at RNA and protein levels.
      Moreover, Overexpression of RRM2B and/or FOXO3 inhibited the proliferation of
      cancer cells. The cancer tissue microarray data also demonstrated a strong
      correlation between the co-expression of FOXO3 plus RRM2B and increased disease
      survival and reduced recurrence or metastasis in lung cancer patients. Our
      results suggest a novel regulatory control of RRM2B function, and imply the
      importance of FOXO signaling pathway in DNA replication modulation. This study
      provides the first time evidence that RRM2B is transcriptionally and functionally
      regulated independent of p53 pathway by FOXO3, and it establishes that FOXO3 and
      RRM2B could be used as predictive biomarkers for cancer progression. 

PMID- 24947619
TI  - The Danish Fracture Database can monitor quality of fracture-related surgery,
      surgeons' experience level and extent of supervision.
AB  - INTRODUCTION: The importance of supervision and of surgeons' level of experience
      in relation to patient outcome have been demonstrated in both hip fracture and
      arthroplasty surgery. The aim of this study was to describe the surgeons'
      experience level and the extent of supervision for: 1) fracture-related surgery
      in general; 2) the three most frequent primary operations and reoperations; and
      3) primary operations during and outside regular working hours. MATERIAL AND
      METHODS: A total of 9,767 surgical procedures were identified from the Danish
      Fracture Database (DFDB). Procedures were grouped based on the surgeons' level of
      experience, extent of supervision, type (primary, planned secondary or
      reoperation), classification (AO Muller), and whether they were performed during
      or outside regular hours. RESULTS: Interns and junior residents combined
      performed 46% of all procedures. A total of 90% of surgeries by interns were
      performed under supervision, whereas 32% of operations by junior residents were
      unsupervised. Supervision was absent in 14-16% and 22-33% of the three most
      frequent primary procedures and reoperations when performed by interns and junior
      residents, respectively. The proportion of unsupervised procedures by junior
      residents grew from 30% during to 40% (p < 0.001) outside regular hours.
      CONCLUSION: Interns and junior residents together performed almost half of all
      fracture-related surgery. The extent of supervision was generally high; however,
      a third of the primary procedures performed by junior residents were
      unsupervised. The extent of unsupervised surgery performed by junior residents
      was significantly higher outside regular hours. FUNDING: not relevant. TRIAL
      REGISTRATION: The Danish Fracture Database ("Dansk Frakturdatabase") was approved
      by the Danish Data Protection Agency ID: 01321.

PMID- 24947620
TI  - Cancer mortality does not differ between migrants and Danish-born patients.
AB  - INTRODUCTION: The aim of this study was to compare cancer mortality among migrant
      patients with cancer mortality in Danish-born patients. MATERIAL AND METHODS:
      This was a historical prospective cohort study. All non-Western migrants (n =
      56,273) who were granted a right to residency in Denmark between 1 January 1993
      and 31 December 1999 were included and matched 1:4 on age and sex with Danish
      born patients. Cancer patients in the cohort were identified through the Danish
      Cancer Registry and deaths and emigrations through the Central Population
      Register. Using a Cox regression model, mean sex-specific hazard ratio (HR) for
      all-cause mortality were estimated by ethnicity; adjusting for age, income, co
      morbidity and disease stage. RESULTS: No significant differences were observed in
      mortality for gynaecological cancers between migrant women (HR = 1.12; 95%
      confidence interval (CI): 0.70-1.80) and Danish-born women. Correspondingly,
      migrant women (HR = 0.76; 95% CI: 0.49-1.17) showed no significant differences in
      breast cancer mortality compared with Danish-born women. Regarding lung cancer,
      neither migrant women (HR = 0.79; 95% CI: 0.45-1.40) nor men (HR = 0.73; 95% CI:
      0.53-1.14) presented statistical variances in mortality rates compared with
      Danish-born patients. Similarly, for colorectal cancer, migrant women (HR = 0.64;
      95% CI: 0.27-1.55) and men (HR = 1.58; 95% CI: 0.75-3.36) displayed no
      significant differences compared with Danish-born patients. CONCLUSION: Different
      trends were observed according to cancer type, but cancer mortality did not
      differ significantly between migrants and Danish-born patients. This may imply
      that the Danish health-care system provides equity in cancer care. FUNDING: The
      study was funded by the University of Copenhagen and Danielsens Fond. TRIAL
      REGISTRATION: not relevant.

PMID- 24947621
TI  - Diagnostic challenges in otogenic brain abscesses.
AB  - INTRODUCTION: Otogenic brain abscess (OBA) is a rare complication to otitis
      media, but one with a potentially devastating outcome. Early diagnosis of OBA is
      crucial for successful treatment. The objective of this study was to determine
      the incidence of OBA in a Danish population and to describe its clinical
      manifestation, management and outcome. MATERIAL AND METHODS: A total of 93
      patients were retrospectively enrolled by diagnosis codes for brain abscess from
      1999 to 2010. Records were reviewed to register age, symptoms, clinical findings,
      co-morbidity, imaging, microbiology and treatment. RESULTS: Seven were found to
      have had an otogenic focus of infection. The incidence of OBA was 1/million, and
      the mean age was 43 years, ranging from ten to 81 years. Five patients had acute
      otitis media and two had infectious cholesteatoma. Four had previously suffered a
      head trauma. The young patients presented with symptoms indicative of meningitis
      and the elderly patients with symptoms resembling a stroke. None of the patients
      were treated with antibiotics before admission to hospital. No mortalities
      occurred, but three had sequelae in the form of hearing loss and/or neurological
      impairment. CONCLUSION: The OBAs manifested with symptoms mimicking meningitis in
      young patients and stroke in elderly patients. Absence of fever does not rule out
      OBA; and regardless of any present ear symptoms, an ear, nose and throat
      examination should be performed without delay to locate the focus of infection
      and to facilitate targeted treatment. FUNDING: not relevant. TRIAL REGISTRATION:
      not relevant.

PMID- 24947622
TI  - Clinical information on admission is insufficient to determine the appropriate
      isolation regimen for acute gastroenteritis.
AB  - INTRODUCTION: The number of admissions for acute gastroenteritis (GE) is
      increasing. The majority of patients pass through a single high-flow emergency
      department (ED) area which increases the risk of spreading GE. The aim of this
      study was to determine the frequency and aetiology of GE for acutely admitted
      patients and to analyse their clinical information focusing on risk indicators of
      contagious aetiology and on the chosen isolation regime to determine if the GE
      required a contact precaution isolation regime. MATERIAL AND METHODS: This study
      included patients above 16 years of age who were admitted acutely within a one
      year study period to a Danish hospital with a catchment population of 231,000
      persons. The following items were analysed: information from the referring
      doctor, diarrhoea, nausea and vomiting and fever history, abdominal pain, prior
      antibiotics, co-morbidity, drugs, travel history, contagious contacts, general
      condition, vital values, isolation regime, final diagnosis and results of stool
      examination. RESULTS: Among 17,531 acute admissions, 1.6% had acute GE and 60% of
      these had stool examinations performed. Only 35% of the patients with GE had
      information about possible GE at referral. Short duration and vomiting may help
      to identify norovirus and antibiotic treatment within the last month to identify
      Clostridium difficile infections. All patients with highly infective GE were
      isolated under a contact precaution regime, but only one in four of the isolated
      patients were actually highly contagious. CONCLUSION: Acute GE is a prevalent
      condition in the ED; a number of patients are isolated unnecessarily, but it is
      difficult to assess correctly who should be isolated and who should not. We
      recommend that further studies be undertaken to define isolation criteria and to
      assess the usefulness of new rapid analysis modalities with a view to reducing
      the isolation period. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 24947624
TI  - Face validity and inter-rater reliability of the Danish version of the modified
      Yale Preoperative Anxiety Scale.
AB  - INTRODUCTION: Preoperative anxiety is common in children and it is associated
      with an adverse post-operative outcome. The modified Yale Preoperative Anxiety
      Scale (m-YPAS) was developed to assess preoperative anxiety in children. The
      purpose of this study was to translate and adapt the m-YPAS to Danish cultural
      and linguistic conditions and to test its face validity and inter-rater
      reliability in a clinical setting. MATERIAL AND METHODS: Translation was done in
      accordance with the WHO guidelines. Face validity and linguistic challenges were
      resolved in a focus group with five nurse anaesthetists. Inter-rater reliability
      for the subscales in the m-YPAS was determined at two different time points by
      using weighted kappa (kappaw) statistics, whereas agreement on the overall
      weighted scores was calculated using the intraclass correlation coefficient
      (ICC). The inter-rater reliability test was done by a paediatric
      anaesthesiologist consultant, a psychiatrist and the first author. RESULTS: The
      Danish version of the m-YPAS was considered suitable and its face validity was
      satisfactory. Inter-rater reliability analysis revealed that inter-observer
      agreement among three independent raters was good (induction 1: kappaw: 0.63
      0.98, ICC = 0.92; induction 2: kappaw: 0.72-0.96, ICC = 0.92). CONCLUSION:
      Standardised and validated assessment tools are needed to evaluate interventions
      to reduce preoperative anxiety in children. A Danish version of the m-YPAS now
      exists, and preliminary testing has demonstrated a satisfactory face validity and
      inter-rater reliability. FUNDING: The study was supported by grants from
      TrygFonden (Grant number: j.no.7-11-1292). TRIAL REGISTRATION: The Danish Data
      Protection Agency, the Central Denmark Region, has approved the study (j.no.:
      2007-58-0010).

PMID- 24947623
TI  - Early results and future challenges of the Danish Fracture Database.
AB  - INTRODUCTION: The Danish Fracture Database (DFDB) was established in 2011 to
      establish nationwide prospective quality assessment of all fracture-related
      surgery. In this paper, we describe the DFDB's setup, present preliminary data
      from the first annual report and discuss its future potential. MATERIAL AND
      METHODS: The DFDB collaboration includes 13 hospitals and covers a population of
      3.7 million. Data registration is performed online by the surgeon following
      surgery, and it includes patient-, trauma- and surgery-related data. Primary
      procedures, reoperations and planned secondary procedures are registered.
      Indication for reoperation is also recorded. The reoperation rate and the one
      year mortality are the primary indicators of quality. RESULTS: Approximately
      10,000 fracture-related surgical procedures were registered in the database at
      the time of presentation of the first annual DFDB report (currently 15,000). 85%
      of all procedures were performed on adult fractures and 15% on paediatric
      fractures. Proximal femur (33%), distal radius (15%) and malleolar fractures
      (12%) were the three most common primary adult fractures. Pain and discomfort
      from orthopaedic hardware, infection and failure of osteosynthesis were the three
      most common indications for reoperation and accounted for 34%, 14% and 13%,
      respectively. CONCLUSION: The DFDB is an online database for registration of
      fracture-related surgery that allows for basic quality assessment of surgical
      fracture treatment and large-scale observational research by registering primary
      surgery, reoperations and planned secondary procedures. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 24947625
TI  - Effect of closure of the mesenteric defect during laparoscopic gastric bypass and
      prevention of internal hernia.
AB  - INTRODUCTION: The aim of this study is to evaluate the benefits and disadvantages
      of closing the mesenteric defects during gastric bypass to avoid internal
      herniation (IH). MATERIAL AND METHODS: The study is performed as a single-centre,
      randomised, controlled, blinded trial. Patients are randomly assigned to either
      conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) without closing the
      mesenteric defects (n = 250) or RYGB with closing of the defects with hernia
      clips (n = 250). Follow-up is conducted at six months, one year, two years and
      five years after RYGB. The primary endpoint is the incidence of IH. CONCLUSION:
      This study will be the first Danish, randomised, controlled study comparing
      conventional LRYGB with and without closure of the mesenteric defects. The
      results will contribute to evidence-based recommendations for the prevention of
      IH. FUNDING: not relevant. TRIAL REGISTRATION: The study was registered with the
      Danish Data Protection Agency (SN-10-2012) and The Central Denmark Regional
      Committees on Biomedical Research Ethics (1-01-83-0209-12, SJ-284). The study is
      registered with clinicaltrials.gov: NCT01595230.

PMID- 24947626
TI  - Current organisation of follow-up does not meet cancer patients' needs.
AB  - INTRODUCTION: For cancer patients, traditional follow-up care is considered
      unsuitable and unsustainable. The patient perspective seems often to be absent in
      the ongoing debate about alternative strategies for follow-up care. Based on a
      national survey from 2012, the objective of this study was to examine cancer
      patients' support needs regarding physiological and emotional problems during
      follow-up and to identify factors associated with their needs and any unmet
      needs. MATERIAL AND METHODS: Patients diagnosed with cancer in the period from
      April to September 2010 were invited to participate. A total of 4,401 patients
      responded (response rate = 64%). The risks in terms of prevalence rate ratios of
      having needs and unmet needs for both physiological and emotional problems were
      estimated using the Poisson regression. RESULTS: The study showed that 60% of the
      patients had needs for support regarding physiological and emotional problems,
      and half of the patients reported unmet needs. Younger patients and patients with
      co-morbidity were more likely to report needs and unmet needs for physiological
      and emotional support. Treatment complexity and setting of follow-up were not
      associated with unmet needs. CONCLUSION: The study underlines that the current
      organisation of follow-up does not meet cancer patients' needs. Several factors
      are associated with both needs and unmet needs. Hence, a more sustainable
      approach for follow-up care may consist in stratification tailored to the
      patients' different needs. In such an approach, more focus should be on age
      specific needs and the impact of co-morbidity. FUNDING: The study is funded by
      the Danish Cancer Society. TRIAL REGISTRATION: The study was approved by the
      Danish Data Protection Agency (J. no. 2010-41-4694). According to the Danish Act
      on Research Ethics Review of Health Research Projects (S. 8(3) of Act No. 402 of
      28 May 2003), no ethical approval was needed.

PMID- 24947627
TI  - An interferon-gamma release assay test performs well in routine screening for
      tuberculosis.
AB  - INTRODUCTION: A positive interferon-gamma release assay (IGRA) is regarded as
      proof of latent Mycobacterium tuberculosis infection. We conducted an evaluation
      of the IGRA test "T-SPOT.TB" to test its performance during clinical routine use
      by analysing the positivity rate and odds, effect of season and sensitivity.
      MATERIAL AND METHODS: Data from T-SPOT.TB testing together with age and test
      indications (anti-tumour necrosis factor alpha (TNFalpha) candidate, contact
      investigation or suspicion of tuberculosis (TB)) were combined with mycobacteria
      culture results. RESULTS: A total of 1,809 patients were tested. Conclusive
      results were achieved for 1,780 patients (98.4%). Among these, 4.6% of anti
      TNFalpha candidates, 19.3% of contacts and 24.4% of TB suspects tested positive.
      Compared with anti-TNFalpha candidates, the odds for a positive result were
      significantly higher for contact investigations (odds ratio (OR), mean (95%
      confidence interval): 4.93 (3.11-7.81)) and TB suspects (OR: 6.83 (4.33-10.77)).
      Elevated odds of an inconclusive test were found during autumn and winter periods
      (OR: 2.53 (1.58-4.05)) and for patients > 75 years of age (OR: 2.66 (1.43-4.94))
      and < 6 years of age (OR: 3.35 (1.58-7.09)). In all, 41 of 43 culture-verified M.
      tuberculosis infections tested positive with one false negative. CONCLUSION:
      During routine testing, inconclusive tests were rare, but more frequent during
      autumn/winter periods and for patients < 6 and > 75 years of age. The T-SPOT.TB
      showed a high sensitivity in culture-verified TB, although false negative results
      did occur. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 24947628
TI  - Predictive validity of neurotic disorders: a 50-year follow-up study.
AB  - INTRODUCTION: In 1965, Erling Jacobsen (1919-1988) defended his doctoral thesis
      on neurosis in which he tested the psychoanalytic theory of eridophobia as an
      internalising hostility factor with a specific causality for anxiety neurosis. He
      found no marked difference between anxiety neurosis and obsessive-compulsive
      neurosis, which, however, both differed from hysterical neurosis. The aim of this
      follow-up study was to evaluate to which extent anxiety neurosis and obsessive
      compulsive neurosis when compared with hysterical neurosis co-existed with
      depression, both at the level of diagnostic behaviour, including committed
      suicide, and with regard to symptom profile. MATERIAL AND METHODS: A total of 112
      patients were followed on the Danish Central Psychiatric Research Register and
      the Danish Cause of Death Register with regard to their diagnostic behaviour. In
      a subset of the sample (n = 24), the patients were assessed using the Hopkins
      Symptom Checklist (SCL)-90. RESULTS: Both at the diagnostic level, including
      suicide rate, and at the level of symptom severity (SCL-90), anxiety neurosis and
      obsessive-compulsive neurosis were similar, in contrast to hysterical neurosis
      which had no more association with the other two categories of neurosis than
      would be expected by chance. CONCLUSION: Anxiety neurosis and obsessive
      compulsive neurosis are more severe disorders than hysterical neurosis, both in
      terms of symptom profile and depression, including suicidal behaviour. The
      identified suicides were committed within the first two decades after discharge
      from the index hospitalisation. FUNDING: Poul M. Faergemann's Grant and the
      Neurosis Grant of 22 July 1959. TRIAL REGISTRATION: not relevant.

PMID- 24947629
TI  - Treatment of chronic upper limb ischaemia is safe and results are good.
AB  - INTRODUCTION: Chronic ischaemia of the upper extremity is rare, and only a few
      small studies are published on results after revascularisation. We found it of
      interest to present this larger population-based registry-study of patients
      treated for chronic ischaemia of the upper limb by open or endovascular
      procedures. MATERIAL AND METHODS: A total of 101,725 primary arterial vascular
      procedures in the Danish National Vascular Registry (Karbase) were recorded from
      1.1.1993 to 31.12.2011. Of these, a total of 453 (0.4%) procedures were performed
      for chronic stenotic disease of the proximal arteries of the upper limb, 233
      endovascularly and 220 by open surgery. RESULTS: Open reconstructions: Two
      patients died within 30 days, which is equivalent to a mortality rate of 0.9%.
      Six (2.7%) reconstructions occluded before discharge. Complications were observed
      in 41 patients (19%); the complications were predominantly related to surgical
      wound. At follow-up, 74 (70%) had no symptoms. Endovascular reconstructions:
      There were six deaths within the first 30 days, which is equivalent to an early
      mortality rate of 2.6%. Four (2%) reconstructions occluded before discharge.
      Complications were observed for 23 (10%) patients; the complications were
      predominantly of neurovascular origin. At follow-up, 90 (74%) had no symptoms.
      The one-year survival was 95% with no difference between the two groups.
      CONCLUSION: Chronic ischaemia of the upper limb can be treated both with open
      surgery and endovascularly with acceptable results. There was an excellent one
      year patency rate for the patients who showed up for follow-up; the patency rate
      was comparable to that reported in the literature. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 24947630
TI  - Impact of cleaning before obtaining midstream urine samples from children.
AB  - INTRODUCTION: Microbiological documentation of one uropathogenic bacterium in
      significant numbers in urine from patients with typical symptoms is the gold
      standard for diagnosing urinary tract infection (UTI). Cleaning before collecting
      midstream urine (MSU) is reported not to reduce the risk of contaminating the
      sample and was therefore omitted at Hvidovre Hospital as from the autumn of 2006.
      We evaluate if no cleaning increased the risk of contamination in the Department
      of Paediatrics. MATERIAL AND METHODS: A total of 1,858 patients aged 0-15 years
      who were suspected of UTI delivered two MSUs within 24 h. In 2004-2006 ("cleaning
      period"), 523 children were cleaned before obtaining two MSUs, contrary to the
      1,335 children included in 2008-2010 ("non-cleaning period"). Significant
      bacteriuria was defined as at least 10,000 colony-forming units/ml of the same
      uropathogenic bacterium in two MSUs in monoculture. Contamination was defined as
      all other microbiological findings. RESULTS: The procedure of no cleaning before
      sampling increased the risk of contamination in 0-9.9-year-old children from 43%
      to 49% (p = 0.034); and specifically in 0-9.9-year-old girls, the risk of
      contamination increased from 47% to 55% (p = 0.018). No significant effect was
      demonstrated in 10-15-year-old girls (p = 1.0) or in boys, independent of age (p
      = 0.19). In both periods, 31% of paired MSUs from the same child were without any
      bacterial or fungal growth. CONCLUSION: Cleaning before collecting urine from
      girls younger than ten years of age is recommended to minimise the risk of
      contamination. Cleaning was without effect on children aged 10-15 years. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 24947631
TI  - Patients and general practitioners have different approaches to e-mail
      consultations.
AB  - INTRODUCTION: The few extant Danish studies on e-mail consultations were
      undertaken before it became manda-tory under Danish law to offer patients this
      form of consultation. This study investigates the ways in which patients and
      general practitioners communicate with each other by e-mail, explores factors
      influencing this means of communication and puts into perspective the potential
      of e-mail consultations in patient treatment. MATERIAL AND METHODS: The study is
      explorative and based on an individual interview and four qualitative focus group
      interviews. The empirical data were analysed from a social constructivist and a
      practice-theoretical approach. RESULTS: The study indicated that patients wanted
      to be able to use the general practitioner (GP) as a sparring partner in e-mail
      consultations. They expected a reply in case of uncertainties. The GPs found it
      difficult to handle complicated medical problems by e-mail and they tended to
      send a standard reply. A number of patients perceived the wording of the standard
      reply as a rejection of their problem. Patients highlighted the logistical
      advantages of e-mail consultations, the physical separation of doctor and patient
      which made it easier for them to disclose psychological or intimate issues. The
      GPs preferred short uncomplicated questions with no option for the patient to
      enter into a discussion. CONCLUSION: Patients and GPs have different approaches
      to e-mail. The development of clear guidelines for patients and revised
      guidelines for GPs regarding e-mail consultations is therefore recommended.
      FUNDING: not relevant. TRIAL REGISTRATION: journal no. 2012-41-0063 with the
      Danish Data Protection Agency.

PMID- 24947632
TI  - Valid and complete data on endometrial cancer in the Danish Gynaecological Cancer
      Database.
AB  - INTRODUCTION: It is a comparative register study designed for data validation of
      surgery, pathology and recurrence for endometrial cancer in the Danish
      Gynaecological Cancer Database (DGCD) in the 2005-2009 period. The main outcomes
      were completeness of the data registered in the DGCD, agreement concerning data
      reported and comparability between the DGCD and a definite reference. MATERIAL
      AND METHODS: DGCD data on women with endometrial cancer or adenomatous
      hyperplasia supplemented with patient charts for data on recurrence were
      retrieved and compared with a definite reference (the pathology report and
      clinical journals). RESULTS: The completeness of data on pathology and surgery
      reported to the DGCD was 97.3%. The comparability between the DGCG and the
      definite reference was 94.4%. The agreement for the reported data in the DGCD was
      88.3%. For recurrence, the comparability was 94.5% and the agreement was 71.6%.
      Completeness could not be determined due to the design of the database, where
      recurrence is composed of optional variables only. CONCLUSION: The data on
      endometrial cancer registered in the DGCD regarding surgery and pathology are
      valid and complete, and they provide a solid base for research. Due to the
      relatively infrequent incidence of recurrences, and the fact that these are
      rarely entered into the database when they do occur, agreement concerning
      recurrence is low. Based on this study, the DGCD cannot alone provide information
      on recurrence that will give a reliable foundation for research. FUNDING: Funding
      was provided by the Health Research Fund of the Region of Central Jutland and the
      Department of Gynaecology and Obstetrics, Aarhus University Hospital. TRIAL
      REGISTRATION: not relevant.

PMID- 24947633
TI  - The clinical effects of closure of the hernia gap after laparoscopic ventral
      hernia repair: protocol for a randomised controlled trial.
AB  - INTRODUCTION: Closure of the hernia gap in laparoscopic ventral hernia repair
      before mesh reinforcement has gained increasing acceptance among surgeons despite
      creating a tension-based repair. Beneficial effects of this technique have been
      reported sporadically, but no evidence is available from randomised controlled
      trials. The primary purpose of this paper is to compare early post-operative
      activity-related pain in patients undergoing laparoscopic ventral hernia repair
      with closure of the gap with patients undergoing standard laparoscopic ventral
      hernia repair (non-closure of the gap). Secondary outcomes are patient-rated
      cosmesis and hernia-specific quality of life. METHODS: A randomised, controlled,
      double-blinded study is planned. Based on power calculation, we will include 40
      patients in each arm. Patients undergoing elective laparoscopic umbilical,
      epigastric or umbilical trocar-site hernia repair at Hvidovre Hospital and Herlev
      Hospital, Denmark, are invited to participate. CONCLUSION: The gap closure
      technique may induce more post-operative pain than the non-closure repair, but it
      may also be superior with regard to other important surgical outcomes. No studies
      have previously investigated closure of the gap in the setting of a randomised
      controlled trial. FUNDING: The study is funded by The University of Copenhagen
      and private foundations. TRIAL REGISTRATION: NCT01962480 (clinicaltrials.gov).

PMID- 24947634
TI  - Good results after laparoscopic marsupialisation of simple liver cysts.
AB  - INTRODUCTION: Large simple liver cysts often tend to be symptomatic with pain
      being the most common symptom. MATERIAL AND METHODS: This was a retrospective
      study of patients who had intended laparoscopic surgery for liver cysts between
      December 2007 and December 2012 at a single institution. RESULTS: A total of 31
      patients (27 women, four men) had surgery. The median age was 61 years (range 27
      81 years). The diagnosis was based on the findings at computed tomography (CT) in
      15 patients (49%), at ultrasonography in 11 (35%), at both CT and ultrasound in
      four (13%) and at magnetic resonance imaging (MRI) in one (3%). Indication for
      surgery was upper abdominal pain (n = 27) and abdominal discomfort (n = 4). The
      laparoscopic approach was successful in 29 patients (94%). The two conversions to
      open surgery were necessary due to peritoneal adherences. The median post
      operative hospital stay was one day (range 1-14 days). Histological evaluation
      revealed 29 non-neoplastic cysts (94%) and two cyst adenomas (6%). Two patients
      had minor post-operative complications, but none needed re-operation. There was
      no 30-day mortality. The median follow-up time was 28 months (range 1-60 months).
      At follow-up, 26 patients (84%) were symptom-free. Of the five patients with re
      occurrence of symptoms, three had a re-operation. The remaining two refrained
      from new surgery. CONCLUSION: Laparoscopic marsupialisation of simple liver cysts
      has a high success rate in terms of pain relief, and it is a safe procedure with
      a short post-operative hospital stay. FUNDING: not relevant. TRIAL REGISTRATION:
      Study reported to Danish Data Protection Agency via Region of Southern Denmark
      (case no. 13/8542).

PMID- 24947635
TI  - Systemic changes in neovascular age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a leading cause of visual impairment in
      the aged population worldwide. The mechanisms underlying this multifactorial and
      heterogenic disease are complex and incompletely understood. There is increasing
      evidence to suggest that regulatory differences in the immune system are involved
      in the development of the various subtypes of AMD. The purpose of this thesis was
      to identify some of these potential differences in patients with early or late
      (wet, dry, or fibrotic) AMD. Specifically, we sought to determine differences in
      1) expression of regulators of the complement pathway (CD46, CD55, and CD59) on
      circulating leukocytes; 2) expression of microglia-inhibitory proteins (CD200 and
      CD200R) on circulating leukocytes; and 3) plasma concentrations of 25
      hydroxyvitamin D, a factor known to inhibit angiogenesis, fibrosis, inflammation,
      and oxidation. All participants underwent a semi-structured interview and
      detailed retinal imaging. Fresh venous blood was obtained and the frequency of
      cells expressing the proteins in question was determined using flow cytometry.
      Plasma 25-hydroxyvitamin D was measured using liquid chromatography-tandem mass
      spectrometry. Also, genotyping as performed in order to determine the frequency
      of certain single-nucleotide polymorphisms in the vitamin D metabolism. Patients
      with wet AMD were found to have statistically significant lower frequencies of
      CD46 and CD59 on CD14+monocytes and higher frequencies of CD200 on CD11b+
      monocytes compared to control individuals without AMD (p = 0.0070 and p = 0.047,
      respectively). Moreover, we found a lower frequency of CD46 on CD45+lymphocytes
      in patients with wet AMD and subretinal fibrosis compared to patients with wet
      AMD without fibrosis (p = 0.010). Vitamin D status was not different across AMD
      subgroups; however, the presence of subretinal fibrosis in patients with wet AMD
      was associated with a statistically significant lower concentration of 25
      hydroxyvitamin D (p < 0.001). Our results suggest that inadequate systemic immune
      modulation is an important pathogenic mechanism in the aetiology of AMD.
      Moreover, some differences in protein expression and vitamin D status appear to
      be related to the phenotypical diversity of AMD, proposing that different
      mechanisms may underlie the different subtypes of AMD. 

PMID- 24947637
TI  - Bard Meridian filter fracture.

PMID- 24947636
TI  - Validation of a patient-level medication regimen complexity index as a possible
      tool to identify patients for medication therapy management intervention.
AB  - BACKGROUND: The Medication Regimen Complexity Index (MRCI) is a 65-item
      instrument that can be used to quantify medication regimen complexity at the
      patient level, capturing all prescribed and over-the-counter medications.
      Although the MRCI has been used in several studies, the narrow scope of the
      initial validation limits application at a population or clinical practice level.
      PURPOSE: To conduct a MRCI validation pertinent to the desired clinical use to
      identify patients for medication therapy management interventions. METHODS: An
      expert panel of clinical pharmacists ranked medication regimen complexity for two
      samples of cases: a single-disease cohort (diabetes mellitus) and a multiple
      disease cohort (diabetes mellitus, hypertension, human immunodeficiency virus
      infection, geriatric depression). Cases for expert panel review were selected
      from 400 ambulatory clinic patients, and each case description included data that
      were available via claims or electronic medical records (EMRs). Construct
      validity was assessed using patient-level MRCI scores, medication count, and
      additional patient data. Concordance was evaluated using weighted kappa agreement
      statistic, and correlations were determined using Spearman rank-order correlation
      coefficient (rho) or Kendall tau. RESULTS: Moderate to good concordance between
      patient-level MRCI scores and expert medication regimen complexity ranking was
      observed (claims data, consensus ranking: single-disease cohort 0.55, multiple
      disease cohort 0.63). In contrast, only fair to moderate concordance was observed
      for medication count (single-disease cohort 0.33, multiple-disease cohort 0.48).
      Adding more-detailed administration directions from EMR data did not improve
      concordance. MRCI convergent validity was supported by strong correlations with
      medication count (all cohorts 0.90) and moderate correlations with morbidity
      measures (e.g., all cohorts; number of comorbidities 0.46, Chronic Disease Score
      0.46). Nonsignificant correlation of MRCI scores with age and gender (all cohorts
      0.08 and 0.06, respectively) supported MRCI divergent validity. LIMITATIONS: This
      study used cross-sectional, retrospective patient data for a small number of
      patients and clinical pharmacists from only two universities; therefore, results
      may have limited generalizability. CONCLUSIONS: The patient-level MRCI is a valid
      tool for assessing medication regimen complexity that can be applied by using
      data commonly found in claims and EMR databases and could be useful to identify
      patients who may benefit from medication therapy management.

PMID- 24947638
TI  - Early pregnancy exposure to antihistamines and risk of congenital heart defects:
      results of two case-control studies.
AB  - We aimed to study the association between use of antihistamines in early
      pregnancy and congenital heart defects (CHD) in the offspring. DESIGN: Two case
      control studies. SETTING: HAVEN study, Erasmus MC, University Medical Centre,
      Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center
      Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410
      controls without congenital malformations from the HAVEN study and replicated the
      analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry.
      Information about antihistamine use in early pregnancy and potential confounders
      was obtained from questionnaires postpartum. We calculated the association
      between antihistamines and CHD risk by multivariable logistic regression
      analysis. MAIN OUTCOME MEASURES: Odds ratios (OR) with 95% confidence intervals
      (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were
      associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly
      atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and
      perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4).
      Mothers with severe nausea who did not use antihistamines had a reduced risk (OR
      0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an
      almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association
      between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95%
      CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We
      found a positive association between antihistamine use in early pregnancy and CHD
      risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

PMID- 24947639
TI  - Ulcerative colitis neoplasia is not associated with common inflammatory bowel
      disease single-nucleotide polymorphisms.
AB  - BACKGROUND: Neoplasia complicating ulcerative colitis (UC-neoplasia) is a problem
      that is poorly addressed by present surveillance techniques. The association of
      greater than 300 single nucleotide polymorphisms (SNPs) with inflammatory bowel
      disease (IBD) suggests the possibility that certain genetic polymorphisms might
      identify patients with UC destined for malignant degeneration. This present study
      tested the hypothesis that presently known IBD-associated SNPs may correlate with
      UC-neoplasia. MATERIALS AND METHODS: A total of 41 patients with UC-neoplasia
      (mean age 56 +/- 2.1 years) were identified from our divisional IBD Biobank (low
      grade dysplasia n = 13, high-grade dysplasia n = 8, colorectal cancer [CRC] n =
      20). These patients were individually age, sex, and disease duration matched with
      UC patients without neoplasia. Primary sclerosing cholangitis and family history
      of CRC were recorded. Patients were genotyped for 314 of the most commonly IBD
      associated SNPs by a custom SNP microarray. Logistic regression and Fischer exact
      test were used for statistical analysis. RESULTS: After Bonferroni correction,
      none of the 314 IBD-associated SNPs correlated with UC-neoplasia when compared
      with matched UC controls. The incidence of primary sclerosing cholangitis was
      greater in the UC-neoplasia group (10/41, 24% vs 3/41, 7%; P = .03) compared with
      UC controls. The severity of neoplasia (low grade dysplasia versus high grade
      dysplasia versus CRC) correlated with disease duration (7.9 vs 13.4 vs 20.7
      years, respectively). CONCLUSION: The lack of correlation between well-known IBD
      associated SNPs and UC-neoplasia demonstrated in this study suggests that the
      development of neoplasia in patients with UC is associated with genetic
      determinants other than those that predispose to inflammation or results from
      posttranslational modifications or epigenetic factors rather than germline
      polymorphisms.

PMID- 24947642
TI  - Risk factors for hematoma after thyroidectomy: results from the nationwide
      inpatient sample.
AB  - BACKGROUND: Hematoma after thyroidectomy is a potentially lethal complication. We
      sought to evaluate risk factors for hematoma formation using the Nationwide
      Inpatient Sample. We hypothesized that certain risk factors could be identified
      and that this information would be useful to surgeons. METHODS: The Nationwide
      Inpatient Sample database was queried for patients who underwent thyroidectomy
      from 1998 to 2010. Bivariate analysis was used to compare patients with and
      without hematoma. Logistic regression was performed to identify important
      predictors of hematoma. RESULTS: There were 150,012 patients. The rate of
      hematoma was 1.25%. Female sex and high-volume hospitals were important for
      decreased hematoma risk (odds ratio 0.61[0.54-0.69] and 0.71 [0.56-0.83],
      respectively). Black race, age >45 years, inflammatory thyroid disease, partial
      thyroidectomy, chronic kidney disease, and bleeding disorders increased the risk
      of hematoma (odds ratio 1.37, 1.44, 1.59, 1.69, 1.8, 3.38; respectively). Overall
      mortality was 0.32% for the entire group and 1.34% in patients with postoperative
      hematoma (P < .001). Patients with hematoma after thyroidectomy were 2.94 [1.76
      4.9] times more likely to die than those without hematoma. CONCLUSION: We
      identified risk factors associated with postoperative hematoma after
      thyroidectomy. Such information should be useful for surgeons for predicting
      patients at risk for this potentially lethal complication.

PMID- 24947640
TI  - Selective histone deacetylase-6 inhibition attenuates stress responses and
      prevents immune organ atrophy in a lethal septic model.
AB  - BACKGROUND: An overproduction of corticosterone during severe sepsis results in
      increased apoptosis of immune cells, which may result in relative
      immunosuppression and an impaired ability to fight infections. We have previously
      demonstrated that administration of tubastatin A, a selective inhibitor of
      histone deacetylase-6 (HDAC6), improves survival in a lethal model of cecal
      ligation and puncture (CLP) in mice. The purpose of this study was to
      characterize the effects of this treatment on sepsis-induced stress responses and
      immune function. METHODS: C57BL/6J mice were subjected to CLP, and 1 hour later
      given an intraperitoneal injection of either tubastatin A dissolved in dimethyl
      sulfoxide (DMSO), or DMSO only. Blood samples were collected to measure the
      levels of circulating corticosterone and adrenocorticotropic hormone (ACTH).
      Thymus and long bones (femur and tibia) were subjected to hematoxylin and eosin
      staining, and immunohistochemistry was utilized to detect cleaved-caspase 3 in
      the splenic follicles as a measure of cellular apoptosis. RESULTS: All vehicle
      treated CLP animals died within 3 days, and displayed increased corticosterone
      and decreased ACTH levels compared with the sham-operated group. These animals
      also developed atrophy of thymic cortex with a marked depletion of thymocytes.
      Tubastatin A treatment significantly attenuated the stress hormone abnormalities.
      Treated animals also had significantly lower percentages of thymic atrophy (95.0
      +/- 5.0 vs 42.5 +/- 25.3; P = .0366), bone marrow depletion and atrophy (58.3 +/-
      6.5 vs 25.0 +/- 14.4%; P = .0449), and cellular apoptosis in the splenic
      follicles (41.2 +/- 3.7 vs 28.5 +/- 4.3 per 40* field; P = .0354). CONCLUSION:
      Selective inhibition of HDAC6 in this lethal septic model was associated with a
      significant blunting of the stress responses, with attenuated thymic and bone
      marrow atrophy, and decreased splenic apoptosis. Our findings identify a novel
      mechanism behind the survival advantage seen with tubastatin A treatment.

PMID- 24947641
TI  - Laparoscopy is safe among patients with congestive heart failure undergoing
      general surgery procedures.
AB  - BACKGROUND: Over the past 2 decades, laparoscopy has been established as a
      superior technique in many general surgery procedures. Few studies, however, have
      examined the impact of the use of a laparoscopic approach in patients with
      symptomatic congestive heart failure (CHF). Because pneumoperitoneum has known
      effects on cardiopulmonary physiology, patients with CHF may be at increased
      risk. This study examines current trends in approaches to patients with CHF and
      effects on perioperative outcomes. METHODS: The 2005-2011 National Surgical
      Quality Improvement Program Participant User File was used to identify patients
      who underwent the following general surgery procedures: Appendectomy, segmental
      colectomy, small bowel resection, ventral hernia repair, and splenectomy.
      Included for analysis were those with newly diagnosed CHF or chronic CHF with new
      signs or symptoms. Trends of use of laparoscopy were assessed across procedure
      types. The primary endpoint was 30-day mortality. The independent effect of
      laparoscopy in CHF was estimated with a multiple logistic regression model.
      RESULTS: A total of 265,198 patients were included for analysis, of whom 2,219
      were identified as having new or recently worsened CHF. Of these patients, there
      were 1,300 (58.6%) colectomies, 486 (21.9%) small bowel resections, 216 (9.7%)
      ventral hernia repairs, 141 (6.4%) appendectomies, and 76 (3.4%) splenectomies.
      Laparoscopy was used less frequently in patients with CHF compared with their non
      CHF counterparts, particularly for nonelective procedures. Baseline
      characteristics were similar for laparoscopy versus open procedures with the
      notable exception of urgent/emergent case status (36.4% vs 71.3%; P < .001).
      After multivariable adjustment, laparoscopy seemed to have a protective effect
      against mortality (adjusted odds ratio, 0.45; P = .04), but no differences in
      other secondary endpoints. CONCLUSION: For patients with CHF, an open operative
      approach seems to be utilized more frequently in general surgery procedures,
      particularly in urgent/emergent cases. Despite these patterns and apparent
      preferences, laparoscopy seems to offer a safe alternative in appropriately
      selected patients. Because morbidity and mortality were considerable regardless
      of approach, further understanding of appropriate management in this population
      is necessary.

PMID- 24947644
TI  - Measuring postoperative recovery: what are clinically meaningful differences?
AB  - BACKGROUND: Surgical innovations are introduced to improve "recovery," a complex
      construct often operationalized by the use of patient-reported outcomes. The
      minimal clinically important difference (MCID) is the smallest change in an
      outcome sufficiently important to influence management and is crucial for
      designing and interpreting comparative effectiveness trials. Our objective was to
      generate MCID estimates for three postoperative recovery metrics. METHODS:
      Prospectively collected data on two cohorts of 281 and 130 adult patients
      undergoing abdominal surgery were analyzed. At each of three visits, patients had
      completed the 36-Item Short Form Survey from the RAND Medical Outcomes Study (SF
      36) and either Community Healthy Activities Model Program for Seniors (CHAMPS) or
      the 6-minute walk test (6MWT). The MCID was estimated with an anchor-based
      approach with random effects linear regression models. Patients' rating of their
      own health was used to predict SF-36 domain, CHAMPS, and 6MWT scores. Results are
      reported as MCID (95% confidence interval). RESULTS: On the SF-36 domains
      analyzed, MCIDs were consistently smaller for patients rating their health as
      "excellent" or "very good" (from 8 [6-9] to 15 [12-18]) compared with those for
      patients rating their health as "fair" or "poor" (from 15 [12-19] to 32 [28-36]).
      For CHAMPS, the MCID was 8 kcal/kg/week (7-9), and for the 6MWT, 14 meters (9
      18). CONCLUSION: Plausible MCIDs and ranges around each estimate are provided.
      These values should be considered when planning and interpreting abdominal
      surgery clinical trials where patient-reported outcomes are assessed.

PMID- 24947645
TI  - The influence of obesity on short- and long-term outcomes after laparoscopic
      surgery for colon cancer: a case-matched study of 152 patients.
AB  - BACKGROUND: Despite the increasing prevalence of obesity and colonic diseases,
      the impact of obesity on short-term and oncologic outcomes of laparoscopic
      colorectal surgery still remains unclear. STUDY DESIGN: Seventy-six consecutive
      obese patients with body mass index (BMI) >=30 kg/m(2) who underwent laparoscopic
      colectomy were matched with 76 nonobese patients with BMI <30 kg/m(2).
      Perioperative parameters and oncologic outcomes were analyzed in the two groups.
      RESULTS: Obesity was associated with greater operative time (obese vs nonobese,
      182 +/- 59 vs 157 +/- 55 min, P = .0084) and multivariate analysis identified BMI
      (hazard ratio 2.11, 95% confidence interval 0.64-3.56, P = .0049) as an
      independent predicting factor for operative time together with cancer location
      (hazard ratio 28.6, 95% confidence interval 14.62-42.51, P < .0001). Obesity had
      no adverse influence on overall morbidity (25 vs 21%, P = .563), however, or
      postoperative duration of stay (median 6.0 vs 5.5 days, P = .22). Furthermore,
      the rate of conversion to open procedure was similar between the two groups (9 vs
      9%, P > .99). Regarding oncologic outcomes, there was no statistical difference
      in overall and disease-free survival between the two groups (5-year overall
      survival rate 86 vs 89%, P = .72, 5-year disease survival rate 70 vs 77%, P =
      .70). CONCLUSION: Laparoscopic colonic resection, when performed for selected
      patients, appears to be a safe and reasonable option in obese patients with colon
      cancer resulting in similar short-term and oncologic outcomes as nonobese
      patients.

PMID- 24947646
TI  - Multifaceted interventions improve adherence to the surgical checklist.
AB  - INTRODUCTION: Adherence to surgical safety checklists remains challenging. Our
      institution demonstrated acceptable rates of checklist utilization but poor
      adherence to all checkpoints. We hypothesized that stepwise, multifaceted
      interventions would improve checklist adherence. METHODS: From 2011 to 2013,
      adherence to the 14-point, pre-incision checklist was assessed directly by
      trained observers during three, 1-year periods (baseline, observation #1, and
      observation #2) during which interventions were implemented. Interventions
      included safety workshops, customization of a stakeholder-derived checklist, and
      implementation of a report card system. Chi-square and Kruskal-Wallis tests were
      utilized. RESULTS: Checklist performance was assessed for 873 cases (baseline, n
      = 144; observation #1, n = 373; observation #2, n = 356). Total checkpoint
      adherence increased (from 30% to 78% to 96%; P < .001), as did cases with correct
      completion of all checkpoints (from 0% to 19% to 61%; P < .001). The median
      (interquartile range) number of checkpoints completed per case improved from 4 (3
      5) to 11 (10-12) to 14 (13-14; P < .001). CONCLUSION: A strategic, multifaceted
      approach to perioperative safety significantly improved checklist adherence over
      2 years. Checklist content and process need to reflect local interests and
      operative flow to achieve high adherence rates. Successful checklist
      implementation requires efforts to change the safety culture, stakeholder buy-in,
      and sustained efforts over time.

PMID- 24947643
TI  - Advanced training in laparoscopic abdominal surgery: a systematic review.
AB  - BACKGROUND: Simulation has spread widely this last decade, especially in
      laparoscopic surgery, and training out of the operating room has proven its
      positive impact on basic skills during real laparoscopic procedures. Few articles
      dealing with advanced training in laparoscopic abdominal surgery, however, have
      been published. Such training may decrease learning curves in the operating room
      for junior surgeons with limited access to complex laparoscopic procedures as a
      primary operator. METHODS: Two reviewers, using MEDLINE, EMBASE, and The Cochrane
      Library conducted a systematic research with combinations of the following
      keywords: (teaching OR education OR computer simulation) AND laparoscopy AND
      (gastric OR stomach OR colorectal OR colon OR rectum OR small bowel OR liver OR
      spleen OR pancreas OR advanced surgery OR advanced procedure OR complex
      procedure). Additional studies were searched in the reference lists of all
      included articles. RESULTS: Fifty-four original studies were retrieved. Their
      level of evidence was low: most of the studies were case series and one fifth
      were purely descriptive, but there were eight randomized trials. Pig models and
      video trainers as well as gastric and colorectal procedures were mainly assessed.
      The retrieved studies showed some encouraging trends in terms of trainee
      satisfaction with improvement after training, but the improvements were mainly on
      the training tool itself. Some tools have been proven to be construct-valid.
      CONCLUSION: Higher-quality studies are required to appraise educational value in
      this field.

PMID- 24947647
TI  - Unintentional perioperative hypothermia is associated with severe complications
      and high mortality in elective operations.
AB  - INTRODUCTION: Hypothermia occurs in as many as 7% of elective colorectal
      operations and is an underestimated risk factor for complications and death.
      Rewarming of hypothermic patients alone is not sufficient to prevent such adverse
      events. We investigated the outcomes of patients who became hypothermic (<35
      degrees C) after elective operations and compared them with closely matched,
      nonhypothermic operative patients to better define the impact of hypothermia on
      surgical outcomes, as well as to identify independent risk factors for
      hypothermia. METHODS: We queried the University HealthSystem Consortium (UHC)
      database for elective operative patients who became unintentionally hypothermic
      from October 2008 to March 2012, and identified 707 patients. Exclusion criteria
      were deliberate hypothermia, age <18 years, or death on day of admission.
      Separately, to validate the accuracy of hypothermia coding, we reviewed the
      hospital charts of all University of Louisville Hospital patients with
      hypothermia whose data were submitted to UHC. RESULTS: All patients from UHC with
      a code for hypothermia were indeed unintentionally hypothermic. Hypothermic
      patients undergoing elective operations experienced a 4-fold increase in
      mortality (17.0% vs 4.0%; P < .001) and a doubled complication rate (26.3% vs
      13.9%; P < .001), in which sepsis and stroke increased the most. Several
      independent risk factors for hypothermia were amenable to preoperative
      improvement: anemia, chronic renal impairment, and unintended weight loss.
      Severity of illness on admission, age >65 years, male sex, and neurologic
      disorders also were risk factors. CONCLUSION: Hypothermia is associated with an
      increased rate of mortality and complications. Preventive treatment of these risk
      factors before operation and aggressive warming measures in the "at risk"
      population may decrease hypothermia-related morbidity and mortality in elective
      operations. Randomized-controlled trials should be conducted to evaluate the
      impact of aggressive warming measures in the at-risk population.

PMID- 24947648
TI  - Reply to: "the influence of contemporaneous revascularization on biliary
      complications after liver transplantation".

PMID- 24947650
TI  - Morbidity and mortality in patients with esophageal atresia.
AB  - BACKGROUND: This study reports national estimates of population characteristics
      and outcomes for patients with esophageal atresia with or without
      tracheoesophageal fistula (EA/TEF) and evaluates the relationships between
      hospital volume and outcomes. METHODS: Patients admitted within 30 days of life
      who had International Classification of Diseases, 9th Edition, Clinical
      Modification diagnosis and procedure codes relevant to EA/TEF during 1999-2012
      were identified with the Pediatric Health Information System database. Baseline
      demographics, comorbidities, and postoperative outcomes, including predictors of
      in-hospital mortality, were examined up to 2 years after EA/TEF repair. RESULTS:
      We identified 3,479 patients with EA/TEF treated at 43 children's hospitals; 37%
      were premature and 83.5% had >=1 additional congenital anomaly, with cardiac
      anomalies (69.6%) being the most prevalent. Within 2 years of discharge, 54.7%
      were readmitted, 5.2% had a repeat TEF ligation, 11.4% had a repeat operation for
      their esophageal reconstruction, and 11.7% underwent fundoplication. In-hospital
      mortality was 5.4%. Independent predictors of mortality included lower birth
      weight, congenital heart disease, other congenital anomalies, and preoperative
      mechanical ventilation. There was no relationship between hospital volume and
      mortality or repeat TEF ligation. CONCLUSION: This study describes population
      characteristics and outcomes, including predictors of in-hospital mortality, in
      EA/TEF patients treated at children's hospitals across the United States. Across
      these hospitals, rates of mortality or repeat TEF ligation were not dependent on
      hospital volume.

PMID- 24947651
TI  - Morbidity and mortality after total gastrectomy for gastric malignancy using the
      American College of Surgeons National Surgical Quality Improvement Program
      database.
AB  - BACKGROUND: Frequent perioperative morbidity and mortality have been observed in
      randomized surgical studies for gastric cancer, but specific patient factors
      associated with morbidity and mortality after total gastrectomy have not been
      well characterized. METHODS: We queried the American College of Surgeons National
      Surgical Quality Improvement Program database (2005-2011) for all patients with a
      gastric neoplasm undergoing total gastrectomy. Univariate and multivariate
      logistic regression analyses were performed to identify factors associated with
      an increased risk of morbidity or mortality. RESULTS: In 1,165 patients
      undergoing total gastrectomy, 416 patients (36%) experienced a complication, and
      55 died (4.7%) within 30 days of operation. In a reduced multivariate model, age
      >70 years, preoperative weight loss, splenectomy, and pancreatectomy were
      associated with morbidity, whereas age >70 years, weight loss, albumin <3 g/dL,
      and pancreatectomy were associated with mortality (P < .05 each). The number of
      present preoperative risk factors stratified morbidity from 26 to 46%, with an
      adjacent organ resection (splenectomy, pancreatectomy) associated with 56%
      morbidity. Similarly, mortality rates ranged from 0.4% in those without risk
      factors to 5 of 9 patients with all three preoperative factors present. Patients
      undergoing pancreatectomy had a 13% mortality rate. CONCLUSION: Total gastrectomy
      for malignancy is associated with substantial morbidity and mortality.
      Identification of high-risk factors may allow more rational patient selection or
      sequencing of therapy.

PMID- 24947652
TI  - Analysis of parahydrogen polarized spin system in low magnetic fields.
AB  - Nuclear magnetic resonance (NMR) spectra of spin systems polarized either
      thermally or by parahydrogen exhibit strikingly different field dependencies.
      Thermally polarized spin systems show the well-known roof effect, observed when
      reducing magnetic field strengths which precludes the independent determination
      of chemical shift differences and J-coupling constants at low-fields. Quantum
      mechanical analysis of the NMR spectra with respect to polarization method,
      pulsed state preparation, and transition probabilities reveals that spectra of
      parahydrogen polarized systems feature an "inverse roof effect" in the regime
      where the chemical shift difference deltanu is smaller than J. This inverse roof
      effect allows for the extraction of both J-coupling and chemical shift
      information down to very low fields. Based on a two-spin system, the observed non
      linear magnetic field dependence of the splitting of spectral lines is predicted.
      We develop a general solution for the steady state density matrix of a
      parahydrogen polarized three-spin system including a heteronucleus which allows
      explaining experimentally observed (1)H spectra. The analysis of three-spin
      density matrix illustrates two pathways for an efficient polarization transfer
      from parahydrogen to (13)C nuclei. Examination of the experimental data
      facilitates the extraction of all relevant NMR parameters using single-scan, high
      resolution (1)H and (13)C NMR spectroscopy at low fields at a fraction of the
      cost associated with cryogenically cooled high-field NMR spectrometers. 

PMID- 24947653
TI  - Pleural function.

PMID- 24947654
TI  - Three-dimensional parallelization of microfluidic droplet generators for a litre
      per hour volume production of single emulsions.
AB  - This paper looks at the design, fabrication and characterization of stackable
      microfluidic emulsion generators, with coefficients of variation as low as ~6%
      and with production rates as high as ~1 L h(-1). This work reports the highest
      throughput reported in the literature for a microfluidic device with simultaneous
      operation of liquid-liquid droplet generators. The device was achieved by
      stacking several layers of 128 flow-focusing droplet generators, organized in a
      circular array. These layers are interconnected via through-holes and fed with
      designated fractal distribution networks. The proposed layers were milled on
      poly(methylmethacrylate) (PMMA) sheets and the stack was thermo-compression
      bonded to create a three-dimensional device with a high density of generators and
      an integrated hydraulic manifold. The effect of stacking multiple layers was
      studied and the results show that fabrication accuracy has a greater impact on
      the dispersity of the emulsion than the addition of more layers to the stack.
      Particle crystallization of drugs was also demonstrated as a possible application
      of this technology in industry. 

PMID- 24947655
TI  - Testing in EHS: What is the Current Status of Experimentation?
AB  - This paper explores some of the fundamental and practical issues related to the
      behavior of nanoparticles in the environment and their potential impacts on human
      health. In our research we have explored the reactive behaviors of nanoparticles
      with contaminants in the environment, how nanoparticle change in response to
      their environment and time, and how nanoparticles interact with biological
      systems of various types. It has become apparent that researchers often
      underestimate the difficulties of preparing and delivering well characterized
      nanoparticles for specific types of testing or applications. Difficulties arise
      in areas that range from not understanding what imparts the "nano" character of a
      particle to not knowing the impacts of minor species on the properties of high
      surface area materials. Some of our adventures and misadventures serve as
      examples of some of these issues as they relate to providing well defined
      particles for biological studies.

PMID- 24947656
TI  - Management of women with low grade cytology: how reassuring is a normal
      colposcopy examination?
AB  - OBJECTIVES: To determine the rate of cervical intraepithelial neoplasia grade 2
      (CIN2+) in women with low grade cervical cytology and a normal colposcopy
      examination over 3 years of follow-up. DESIGN: Cohort study within a randomised
      controlled trial. SETTING: NHS Cervical Screening Programmes in Grampian, Tayside
      and Nottingham. POPULATION: Eight hundred and eighty-four women aged 20-59 years
      with borderline nuclear abnormalities (BNA) or mild dyskaryosis with a normal and
      adequate colposcopy examination. METHODS: Samples at baseline were tested for 14
      high-risk (Hr) types using GP5+6+ methodology and for HPV 16 and 18 using type
      specific primers. Women were followed up post-colposcopy by cervical cytology at
      6-month intervals in primary care. After 3 years, women were invited for an exit
      colposcopy examination and underwent LLETZ if any colposcopic abnormality was
      identified. MAIN OUTCOME MEASURES: Absolute and relative risks of CIN2+ during
      follow-up and/or at exit colposcopy. RESULTS: The median age was 36 years. The
      absolute risk of developing CIN2+ within 3 years was 1.86 per 100 woman years and
      for CIN3+, 0.64 per 100 woman years. One microinvasive cancer was identified. The
      relative risk (RR) was highest for women with initial mild dyskaryosis who were
      HrHPV-positive (RR 5.86, 95% confidence interval 2.53-13.56) compared with women
      with BNA who were HrHPV-negative. CONCLUSION: For women with low grade cervical
      cytology, the risk of a high grade CIN within 3 years of a normal colposcopy
      examination is low. Women can be reassured that, even with a positive HPV test,
      the risk of developing CIN2 or worse is sufficiently low to return to the routine
      3-year recall.

PMID- 24947659
TI  - Effect of simulated microwave disinfection on the linear dimensional change,
      hardness and impact strength of acrylic resins processed by different
      polymerizing cycles.
AB  - AIM: This study investigated the effect of simulated microwave disinfection (SMD)
      on the linear dimensional changes, hardness and impact strength of acrylic resins
      under different polymerization cycles. METHODS: Metal dies with referential
      points were embedded in flasks with dental stone. Samples of Classico and Vipi
      acrylic resins were made following the manufacturers' recommendations. The
      assessed polymerization cycles were: A-- water bath at 74oC for 9 h; B-- water
      bath at 74oC for 8 h and temperature increased to 100oC for 1 h; C-- water bath
      at 74oC for 2 h and temperature increased to 100oC for 1 h;; and D-- water bath
      at 120oC and pressure of 60 pounds. Linear dimensional distances in length and
      width were measured after SMD and water storage at 37oC for 7 and 30 days using
      an optical microscope. SMD was carried out with the samples immersed in 150 mL of
      water in an oven (650 W for 3 min). A load of 25 gf for 10 sec was used in the
      hardness test. Charpy impact test was performed with 40 kpcm. Data were submitted
      to ANOVA and Tukey's test (5%). RESULTS: The Classico resin was dimensionally
      steady in length in the A and D cycles for all periods, while the Vipi resin was
      steady in the A, B and C cycles for all periods. The Classico resin was
      dimensionally steady in width in the C and D cycles for all periods, and the Vipi
      resin was steady in all cycles and periods. The hardness values for Classico
      resin were steady in all cycles and periods, while the Vipi resin was steady only
      in the C cycle for all periods. Impact strength values for Classico resin were
      steady in the A, C and D cycles for all periods, while Vipi resin was steady in
      all cycles and periods. CONCLUSION: SMD promoted different effects on the linear
      dimensional changes, hardness and impact strength of acrylic resins submitted to
      different polymerization cycles when after SMD and water storage were considered.

PMID- 24947658
TI  - Myopia and level of education: results from the Gutenberg Health Study.
AB  - PURPOSE: To analyze the association between myopia and educational level in an
      adult European cohort. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: A cohort of the Gutenberg Health Study, including 4658 eligible
      enrollees between 35 and 74 years of age. METHODS: We applied a standardized
      protocol entailing a comprehensive questionnaire; thorough ophthalmic, general,
      cardiovascular, and psychological examinations; and laboratory tests, including
      genetic analyses. We documented achievement levels in school education and post
      school professional education. The spherical equivalent (SE) was determined by
      noncycloplegic autorefractometry. We fitted mixed linear models including age,
      gender, and 45 myopia-associated single nucleotide polymorphisms (SNP) as
      covariates. MAIN OUTCOME MEASURES: Prevalence and magnitude of myopia in
      association with years spent in school and level of post-school professional
      education. RESULTS: Individuals who graduated from school after 13 years were
      more myopic (median, -0.5 diopters [D]; first quartile [Q1]/third quartile [Q3], 
      2.1/0.3 D) than those who graduated after 10 years (median, -0.2 D; Q1/Q3, 
      1.3/0.8 D), than those who graduated after 9 years (median, 0.3 D; Q1/Q3, 
      0.6/1.4 D), and than those who never finished secondary school (median, 0.2 D;
      Q1/Q3, -0.5/1.8 D; P<0.001, respectively). The same holds true for persons with a
      university degree (median, -0.6 D; Q1/Q3, -2.3/0.3 D) versus those who finished
      secondary vocational school (median, 0 D; Q1/Q3, -1.1/0.8 D) or primary
      vocational school (median, 0 D; Q1/Q3, -0.9/1.1 D) versus persons without any
      post-school professional qualification (median, 0.6 D; Q1/Q3, -0.4/1.7 D;
      P<0.001, respectively). Of persons who graduated from school after 13 years,
      50.9% were myopic (SE, <=-0.5 D) versus 41.6%, 27.1%, and 26.9% after 10 years,
      in those who graduated after 9 years, and in those who never graduated from
      secondary school, respectively (P<0.001). In university graduates, the proportion
      of myopic persons was higher (53%) than that of those who graduated from
      secondary (34.8%) or primary (34.7%) vocational schools and than in those without
      any professional training (23.9%; P<0.001, respectively). In multivariate
      analyses: higher school and professional levels of education were associated with
      a more myopic SE independent of gender. There was a small effect of age and SNPs.
      CONCLUSIONS: Higher levels of school and post-school professional education are
      associated with a more myopic refraction. Participants with higher educational
      achievements more often were myopic than individuals with less education.

PMID- 24947657
TI  - Microbial production of biopolymers from the renewable resource wheat straw.
AB  - AIMS: Production of poly-beta-hydroxybutyrate (PHB) and the chemical basic
      compound lactate from the agricultural crop 'wheat straw' as a renewable carbon
      resource. METHODS AND RESULTS: A thermal pressure hydrolysis procedure for the
      breakdown of wheat straw was applied. By this means, the wheat straw was
      converted into a partially solubilized hemicellulosic fraction, consisting of
      sugar monomers, and an insoluble cellulosic fraction, containing cellulose,
      lignin and a small portion of hemicellulose. The insoluble cellulosic fraction
      was further hydrolysed by commercial enzymes in monomers. The production of PHB
      from the sugar monomers originating from hemicellulose or cellulose was achieved
      by the isolates Bacillus licheniformis IMW KHC 3 and Bacillus megaterium IMW KNaC
      2. The basic chemical compound, lactate, a starting compound for the production
      of polylactide (PLA), was formed by some heterofermentative lactic acid bacteria
      (LAB) able to grow with xylose from the hemicellulosic wheat straw hydrolysate.
      CONCLUSIONS: Two strains were selected which were able to produce PHB from the
      sugars both from the hemicellulosic and the cellulosic fraction of the wheat
      straw. In addition, some of the LAB tested were capable of producing lactate from
      the hemicellulosic hydrolysate. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      renewable resource wheat straw could serve as a substrate for microbiologically
      produced basic chemicals and biodegradable plastics.

PMID- 24947660
TI  - Evaluation of scientific production in Oral Surgery in Italy from 1998 to 2012.
AB  - INTRODUCTION: Dental research, especially in the field of oral surgery, showed a
      strong and significant increase during the last years. This was probably
      determined by the introduction among the clinicians of different therapeutic
      protocols through biomaterials engineering, and by the large broadcasting of
      scientific knowledge due to new media such as the internet. The aim of this work
      was to analyze the scientific production of a sample of Italian Oral Surgeons
      from 1998 to 2012. MATERIALS AND METHODS: The scientific production of 252 Active
      Members belonging to three associations of Italian Oral Surgery (SIdCO, SIO,
      SICOI) was examined. The number of authors, the number of publications and the
      number of citation were quantified for three periods of 5 years each from the
      first year considered along 15 years. The overall sample was then divided into
      two groups, Academics and Not Academics, in order to differently assess the
      scientific production conducted inside or outside the University. RESULTS: Over
      the years, scientific production increased considerably, with a progression not
      strictly proportional if compared to the number of authors, especially in the
      last 5 years. By spearately considering the Academics and the Not Academics
      authors, the biggest contribution to the scientific production increasingly came
      from the last 5 years, both in terms of authors' and published papers number.
      CONCLUSIONS: The results reported in this bibliometric analysis show how
      scientific research increasingly pursued by clinicians in Oral Surgery in the
      last 15 years.

PMID- 24947661
TI  - Nonwoven polypropylene as a novel extractant phase holder for the determination
      of insecticides in environmental water samples.
AB  - In this work, a novel liquid-phase microextraction approach using nonwoven
      polypropylene as the extraction solvent holder was developed. Nonwoven
      polypropylene, a hydrophobic material, is widely used in the cleanup of oil
      spills. Due to its large surface area, efficient, and full extraction can be
      achieved. Nonwoven polypropylene containing an ionic liquid was used to extract
      benzoylurea insecticides (diflubenzuron, teflubenzuron, flufenoxuron, and
      chlorfluazuron) through vortex-assisted liquid-liquid microextraction. The
      parameters that affected the extraction efficiency included the type and volume
      of the extractant, the extraction time, the time and solvent volume for
      desorption and the mass and surface area of the nonwoven polypropylene. Under the
      optimized conditions, good linearity was obtained, with coefficients of
      determination greater than 0.9996, and the limit of detections of these
      compounds, calculated at S/N = 3, were in the range of 0.73-5.0 ng/mL. The
      recoveries of the four insecticides at two spiked levels ranged from 93.3 to
      102.0%, with relative standard deviations of less than 4.0%. The proposed method
      was then successfully used for the rapid determination of benzoylurea
      insecticides in spiked real water samples before liquid chromatographic analysis.
      The procedure is simple, inexpensive, easy to execute, and can be widely used. 

PMID- 24947662
TI  - WITHDRAWN:Translational Research-Changing the Landscape of Pediatric Nursing.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.pedn.2014.05.008. The duplicate article has therefore
      been withdrawn.

PMID- 24947663
TI  - School-based health center providers' treatment of overweight children.
AB  - This descriptive study was to determine self-reported treatment practices of
      school-based health center (SBHC) providers when caring for overweight/obese
      children. Providers (N=33) from SBHCs in 6 states (AZ, CO, NM, MI, NY, and NC)
      completed a baseline survey before being trained on obesity recommendations. SBHC
      providers reported patient/parent barriers to be more significant to treatment
      than clinician/setting barriers (p<0.0001). Most providers (97%) indicated
      childhood overweight needs treatment, yet only 36% said they initiate treatment
      in children who do not want to control their weight. SBHC providers also did not
      commonly refer overweight/obese children to specialists. 

PMID- 24947664
TI  - A review of the handling of missing longitudinal outcome data in clinical trials.
AB  - The aim of this review was to establish the frequency with which trials take into
      account missingness, and to discover what methods trialists use for adjustment in
      randomised controlled trials with longitudinal measurements. Failing to address
      the problems that can arise from missing outcome data can result in misleading
      conclusions. Missing data should be addressed as a means of a sensitivity
      analysis of the complete case analysis results. One hundred publications of
      randomised controlled trials with longitudinal measurements were selected
      randomly from trial publications from the years 2005 to 2012. Information was
      extracted from these trials, including whether reasons for dropout were reported,
      what methods were used for handing the missing data, whether there was any
      explanation of the methods for missing data handling, and whether a statistician
      was involved in the analysis. The main focus of the review was on missing data
      post dropout rather than missing interim data. Of all the papers in the study, 9
      (9%) had no missing data. More than half of the papers included in the study
      failed to make any attempt to explain the reasons for their choice of missing
      data handling method. Of the papers with clear missing data handling methods, 44
      papers (50%) used adequate methods of missing data handling, whereas 30 (34%) of
      the papers used missing data methods which may not have been appropriate. In the
      remaining 17 papers (19%), it was difficult to assess the validity of the methods
      used. An imputation method was used in 18 papers (20%). Multiple imputation
      methods were introduced in 1987 and are an efficient way of accounting for
      missing data in general, and yet only 4 papers used these methods. Out of the 18
      papers which used imputation, only 7 displayed the results as a sensitivity
      analysis of the complete case analysis results. 61% of the papers that used an
      imputation explained the reasons for their chosen method. Just under a third of
      the papers made no reference to reasons for missing outcome data. There was
      little consistency in reporting of missing data within longitudinal trials.